PMID- 23852312
TI  - Multifaceted aging and rapamycin.

PMID- 23852311
TI  - Neoadjuvant treatment of borderline resectable and non-resectable pancreatic
      cancer.
AB  - Neoadjuvant therapy is increasingly becoming a valid treatment option for
      patients with locally advanced pancreatic cancer (LAPC). In borderline resectable
      disease, neoadjuvant therapy is employed to improve the probability of margin
      clear resections. In non-metastatic, non-resectable pancreatic cancer, treatment
      primarily aims to induce disease control, but may achieve conversion to surgical
      resectability in some patients. Several treatment modalities including
      chemotherapy, chemoradiotherapy (CRT) or the sequential use of both have been
      investigated in numerous, mostly small and non-randomized studies. Nevertheless,
      there is a consistent finding that neoadjuvant therapy can induce resectability
      in up to 30%-40% of LAPC patients. Once resection has been achieved, overall
      survival appears to be comparable to that observed for primarily resectable
      patients. Thus, patient selection evolves as an important aspect of neoadjuvant
      therapy; retrospective analyses identified induction chemotherapy as an
      appropriate tool to define LAPC patients who may benefit most from subsequent
      treatment with CRT. The clinical importance of induction chemotherapy may further
      increase once highly active protocols such as the FOLFIRINOX or the gemcitabine
      plus nab-paclitaxel regimen are introduced into novel multimodality treatment
      concepts. 

PMID- 23852313
TI  - Comparison of two protocols of transcranial magnetic stimulation for treatment of
      chronic tinnitus: a randomized controlled clinical trial of burst repetitive
      versus high-frequency repetitive Transcranial Magnetic Stimulation.
AB  - The aim of the study was to compare the effects of two techniques of repetitive
      Transcranial Magnetic Stimulation (rTMS) to treat chronic tinnitus; continuous
      Theta Burst Stimulation (cTBS) and high-frequency rTMS. In a controlled
      randomized clinical trial, 55 patients with chronic tinnitus were randomly
      divided in two groups. They received four sessions of treatment. cTBS was tested
      on one group and high-frequency rTMS (10 Hz) was tested on the other. Severity of
      the tinnitus was assessed before treatment, after the last treatment session and
      then 1-month later. Both the treatments of high-frequency and cTBS had a
      suppressive effect on tinnitus. However, cTBS was more effective than high
      frequency rTMS (P = 0.001). This study suggests that rTMS even in four sessions
      is effective in reducing tinnitus severity; moreover, compared to high-frequency
      TMS better results can be achieved with cTBS.

PMID- 23852314
TI  - Pentylenetetrazol-induced seizures are exacerbated by sleep deprivation through
      orexin receptor-mediated hippocampal cell proliferation.
AB  - Sleep deprivation has been shown to be an activator of seizures in clinical and
      animal studies. Orexin-A was speculated to be involved in the aggravation of
      seizures by sleep deprivation through the activation of its receptors: orexin-1
      and orexin-2 receptor (OX1R and OX2R, respectively). Therefore, we aimed to
      investigate the effects of pre-treating sleep-deprived Wistar rats with the OX1R
      or OX2R antagonists, SB334867 (30 nM/kg) or TCS OX2 29 (30 nM/kg), respectively,
      followed by a convulsive dose of 50 mg/kg pentylenetetrazol administration
      (seizure induction), on seizure behavior, and hippocampal neurodegeneration and
      cellular proliferation. Our results revealed that treatment with SB334867 or TCS
      OX2 29 significantly prolonged the latency and reduced the duration of seizures,
      while also lowering the mortality rate in sleep-deprived rats exposed to
      pentylenetetrazol. In addition, SB334867 or TCS OX2 29 reduced the damage to
      hippocampal CA3 neurons and the number of bromodeoxyuridine-positive cells in the
      dentate gyrus (particularly in the hilus). Overall, the effect of TCS OX2 29 was
      greater than that of SB334867. Taken together, these data suggest that OX1R and
      OX2R antagonists may alleviate the damage of pentylenetetrazol-induced seizures
      that are exacerbated by sleep deprivation, and furthermore could be associated
      with a reduction of neuronal damage in the hippocampus and the inhibition of
      cellular proliferation in the dentate gyrus.

PMID- 23852315
TI  - Atherogenic consequence of antiepileptic drugs: a study of intima-media
      thickness.
AB  - We intended to evaluate the carotid intima-media thickness (CA-IMT) as a
      surrogate factor for atherogenesis in epileptic patients on enzyme inducer (EI)
      antiepileptic drugs (AEDs) or valproate (VA). The study included 71 patients with
      epilepsy (37 females) aged 27.7 +/- 8.1 and 71 age- and sex-matched non-epileptic
      subjects. Patients with history of at least 2 years antiepileptic treatment were
      enrolled. Subjects with known history of cardiovascular risk factors were not
      included. Thirty-eight patients (21 females) were treated with EI medications and
      33 (16 females) with VA. CA-IMTs were measured by a single sonography system in
      all participants. CA-IMT values were compared between patients with epilepsy and
      the controls and within the patients with epilepsy on VA or EI medications.
      Duration of epilepsy was 10.1 +/- 7.1 years. Patients were treated with their
      current AED for 6.9 +/- 4.8 years. The CA-IMT of patients with epilepsy was
      higher than non-epileptic control subjects on either left (0.502 +/- 0.079 vs.
      0.470 +/- 0.073 mm; p = 0.012) or right side (0.524 +/- 0.078 vs. 0.458 +/- 0.068
      mm; p < 0.001). Patients on VA were younger than those receiving EI medications
      (25.8 +/- 7.1 vs. 29.4 +/- 8.7 years). Age adjusted CA-IMT values of patients on
      VA did not differ from the values of patients receiving EI medications. Duration
      of drug administration did not correlate with CA-IMT values. Patients with
      epilepsy on AEDs are at higher risk for atherogenesis. In the population of this
      study the increased risk of atherogenesis was not attributable to the
      administered AED or duration of treatment.

PMID- 23852316
TI  - Pure midbrain ischemia and hypoplastic vertebrobasilar circulation.
AB  - Isolated midbrain infarction is rare and little is known about etiology and
      patient's long-term follow up. We aimed to describe the clinical features, the
      causative diseases and the outcome of patients with isolated midbrain infarction
      who were admitted to our center, focusing on vascular abnormalities of posterior
      circulation. All patients with first acute ischemic stroke limited to the
      midbrain were included and their demographic features, neurological symptoms,
      neuroimaging data, and cardiovascular risk factors were recorded. Functional
      outcome, using modified Rankin scale, was assessed at discharge and at the 3
      month follow up evaluation. We found nine patients with acute isolated midbrain
      infarction, representing 0.61 % of all ischemic stroke admitted to our center.
      The most common cause of stroke was small-vessel disease (88.8 %). At stroke
      onset, none of the patients had consciousness disturbances, and four patients
      (44.4 %) had gait impairment, five patients (55.5 %) presented with diplopia due
      to involvement of the third nerve or fascicular type of third-nerve palsy, seven
      patients (77.7 %) had vascular anomalies of vertebrobasilar circulation: the most
      frequent was vertebral artery hypoplasia [four patients (44.4 %)]. At follow up
      evaluation, seven patients (77.7 %) had a good functional outcome and no patients
      experienced recurrence of cerebrovascular events. As isolated midbrain infarction
      is uncommon, specific ocular motor signs, mainly third-nerve palsy, may help to
      identify and localize the mesencephalic infarct. Abnormalities in vertebrobasilar
      circulation, such as hypoplastic basilar or vertebral artery, are frequently
      associated with isolated midbrain ischemia. The hypoplastic vertebrobasilar
      system may predispose to posterior ischemic stroke.

PMID- 23852317
TI  - Gun policy and serious mental illness: priorities for future research and policy.
AB  - OBJECTIVE: In response to recent mass shootings, policy makers have proposed
      multiple policies to prevent persons with serious mental illness from having
      guns. The political debate about these proposals is often uninformed by research.
      To address this gap, this review article summarizes the research related to gun
      restriction policies that focus on serious mental illness. METHODS: Gun
      restriction policies were identified by researching the THOMAS legislative
      database, state legislative databases, prior review articles, and the news media.
      PubMed, PsycINFO, and Web of Science databases were searched for publications
      between 1970 and 2013 that addressed the relationship between serious mental
      illness and violence, the effectiveness of gun policies focused on serious mental
      illness, the potential for such policies to exacerbate negative public attitudes,
      and the potential for gun restriction policies to deter mental health treatment
      seeking. RESULTS: Limited research suggests that federal law restricting gun
      possession by persons with serious mental illness may prevent gun violence from
      this population. Promotion of policies to prevent persons with serious mental
      illness from having guns does not seem to exacerbate negative public attitudes
      toward this group. Little is known about how restricting gun possession among
      persons with serious mental illness affects suicide risk or mental health
      treatment seeking. CONCLUSIONS: Future studies should examine how gun restriction
      policies for serious mental illness affect suicide, how such policies are
      implemented by states, how persons with serious mental illness perceive policies
      that restrict their possession of guns, and how gun restriction policies
      influence mental health treatment seeking among persons with serious mental
      illness.

PMID- 23852318
TI  - Correlative microscopy for 3D structural analysis of dynamic interactions.
AB  - Cryo-electron tomography (cryoET) allows 3D visualization of cellular structures
      at molecular resolution in a close-to-physiological state(1). However, direct
      visualization of individual viral complexes in their host cellular environment
      with cryoET is challenging(2), due to the infrequent and dynamic nature of viral
      entry, particularly in the case of HIV-1. While time-lapse live-cell imaging has
      yielded a great deal of information about many aspects of the life cycle of HIV
      1(3-7), the resolution afforded by live-cell microscopy is limited (~200 nm). Our
      work was aimed at developing a correlation method that permits direct
      visualization of early events of HIV-1 infection by combining live-cell
      fluorescent light microscopy, cryo-fluorescent microscopy, and cryoET. In this
      manner, live-cell and cryo-fluorescent signals can be used to accurately guide
      the sampling in cryoET. Furthermore, structural information obtained from cryoET
      can be complemented with the dynamic functional data gained through live-cell
      imaging of fluorescent labeled target. In this video article, we provide detailed
      methods and protocols for structural investigation of HIV-1 and host-cell
      interactions using 3D correlative high-speed live-cell imaging and high
      resolution cryoET structural analysis. HeLa cells infected with HIV-1 particles
      were characterized first by confocal live-cell microscopy, and the region
      containing the same viral particle was then analyzed by cryo-electron tomography
      for 3D structural details. The correlation between two sets of imaging data,
      optical imaging and electron imaging, was achieved using a home-built cryo
      fluorescence light microscopy stage. The approach detailed here will be valuable,
      not only for study of virus-host cell interactions, but also for broader
      applications in cell biology, such as cell signaling, membrane receptor
      trafficking, and many other dynamic cellular processes.

PMID- 23852319
TI  - The synergistic effect of visible light and gentamycin on Pseudomona aeruginosa
      microorganisms.
AB  - Recently there were several publications on the bactericidal effect of visible
      light, most of them claiming that blue part of the spectrum (400 nm-500 nm) is
      responsible for killing various pathogens(1-5). The phototoxic effect of blue
      light was suggested to be a result of light-induced reactive oxygen species (ROS)
      formation by endogenous bacterial photosensitizers which mostly absorb light in
      the blue region(4,6,7). There are also reports of biocidal effect of red and near
      infra red(8) as well as green light(9). In the present study, we developed a
      method that allowed us to characterize the effect of high power green (wavelength
      of 532 nm) continuous (CW) and pulsed Q-switched (Q-S) light on Pseudomonas
      aeruginosa. Using this method we also studied the effect of green light combined
      with antibiotic treatment (gentamycin) on the bacteria viability. P. aeruginosa
      is a common noscomial opportunistic pathogen causing various diseases. The strain
      is fairly resistant to various antibiotics and contains many predicted AcrB/Mex
      type RND multidrug efflux systems(10). The method utilized free-living stationary
      phase Gram-negative bacteria (P. aeruginosa strain PAO1), grown in Luria Broth
      (LB) medium exposed to Q-switched and/or CW lasers with and without the addition
      of the antibiotic gentamycin. Cell viability was determined at different time
      points. The obtained results showed that laser treatment alone did not reduce
      cell viability compared to untreated control and that gentamycin treatment alone
      only resulted in a 0.5 log reduction in the viable count for P. aeruginosa. The
      combined laser and gentamycin treatment, however, resulted in a synergistic
      effect and the viability of P. aeruginosa was reduced by 8 log's. The proposed
      method can further be implemented via the development of catheter like device
      capable of injecting an antibiotic solution into the infected organ while
      simultaneously illuminating the area with light. 

PMID- 23852320
TI  - [Presentation of software for collation of inpatient diurnal pressure profiles in
      glaucoma patients].
AB  - The aim of diurnal pressure profiles is clarification of therapy safety and the
      diagnosis of glaucoma. The evaluation of intraocular pressure curves is part of
      the running assessment. In order to support this evaluation software has been
      developed which, in addition to the digital presentation of intraocular pressure
      curves corrected for corneal thickness also allows immediate statistical
      assessment. After specifying a target pressure it also allows deduction of
      possible therapy recommendations based on the resulting intraocular pressure
      values, the cup/disc ratio and the number of antiglaucoma agents given. In this
      study two collectives were investigated: in the first collective, in addition to
      the previously determined diagnoses, the intraocular pressure, number and time of
      measurements, predetermined target pressure, cup/disc ratio and corneal thickness
      dependent correction values were evaluated. After completing a scoring system
      with respect to agreement of the clinical therapy suggestions with those
      suggestions calculated by the software, the second collective was compared after
      termination of the diurnal pressure profile. Concordance was found in 73 out of
      88 eyes. The digital collation system for profile measurement was found to be
      very well suited for graphical and clinical documentation of diurnal pressure
      profile curves. Therapy decisions can be deduced from the available data and
      supported by the software. 

PMID- 23852321
TI  - Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk
      myeloma: analysis of SWOG trial S0115.
AB  - We designed a trial using two sequential cycles of modified high-dose melphalan
      at 100 mg/m(2) and autologous SCT (mHDM/SCT) in AL amyloidosis (light-chain
      amyloidosis, AL), AL with myeloma (ALM) and host-based high-risk myeloma (hM)
      patients through SWOG-0115. The primary objective was to evaluate OS. From 2004
      to 2010, 93 eligible patients were enrolled at 17 centers in the United States
      (59 with AL, 9 with ALM and 25 with hM). The median OS for patients with AL and
      ALM was 68 months and 47 months, respectively, and has not been reached for
      patients with hM. The median PFS for patients with AL and ALM was 38 months and
      16 months, respectively, and has not been reached for patients with hM. The
      treatment-related mortality (TRM) was 12% (11/93) and was observed only in
      patients with AL after SCT. Grade 3 and higher non-hematologic adverse events
      were experienced by 81%, 67% and 57% of patients with AL, ALM and hM,
      respectively, during the first and second HDM/SCT. This experience demonstrates
      that with careful selection of patients and use of mHDM for SCT in patients with
      AL, ALM and hM, even in the setting of a multicenter study, OS can be improved
      with acceptable TRM and morbidity. 

PMID- 23852322
TI  - Visual contribution to the high-frequency human angular vestibulo-ocular reflex.
AB  - The vestibulo-ocular reflex (VOR) acts to maintain images stable on the retina by
      rotating the eyes in exactly the opposite direction, but with equal magnitude, to
      head velocity. When viewing a near target, this reflex has an increased response
      to compensate for the translation of the eyes relative to the target that acts to
      reduce retinal image slip. Previous studies have shown that retinal velocity
      error provides an important visual feedback signal to increase the low-frequency
      (<1 Hz) VOR response during near viewing. We sought to determine whether initial
      eye position and retinal image position error could provide enough information to
      substantially increase the high-frequency VOR gain (eye velocity/head velocity)
      during near viewing. Ten human subjects were tested using the scleral search coil
      technique during horizontal head impulses under different lighting conditions
      (constant dark, strobe light at 0.5, 1, 2, 4, 10, 15 Hz, constant light) while
      viewing near (9.5 +/- 1.3 cm) and far (104 cm) targets. Our results showed that
      the VOR gain increased during near viewing compared to far viewing, even during
      constant dark. For the near target, there was an increase in VOR gain with
      increasing strobe frequency from 1.17 +/- 0.17 in constant dark to 1.36 +/- 0.27
      in constant light, a 21 +/- 9 % increase. For the far target, strobe frequency
      had no effect. Presentation order of strobe frequency (i.e. 0.5-15 vs. 15-0.5 Hz)
      did not affect the gain, but it did affect the vergence angle (angle between the
      two eye's lines of sight). The VOR gain and vergence angles were constant during
      each trial. Our findings show that a retinal position error signal helps increase
      the vergence angle and could be invoking vestibular adaptation mechanisms to
      increase the high-frequency VOR response during near viewing. This is in contrast
      to the low-frequency VOR that depends more on retinal velocity error and
      predictive adaptation mechanisms.

PMID- 23852323
TI  - Modulation of muscle sympathetic nerve activity by low-frequency physiological
      activation of the vestibular utricle in awake humans.
AB  - We recently showed that selective stimulation of one set of otolithic organs
      those located in the utricle, sensitive to displacement in the horizontal axis
      causes a marked entrainment of skin sympathetic nerve activity (SSNA). Here, we
      assessed whether muscle sympathetic nerve activity (MSNA) is similarly modulated.
      MSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles
      of the common peroneal nerve in 12 awake subjects, seated (head vertical, eyes
      closed) on a motorised platform. Slow sinusoidal accelerations-decelerations (+/
      4 mG) were applied in the X (antero-posterior) or Y (medio-lateral) direction at
      0.08 Hz. Cross-correlation analysis revealed partial entrainment of MSNA:
      vestibular modulation was 32 +/- 3 % for displacements in the X-axis and 29 +/- 3
      % in the Y-axis; these were significantly smaller than those evoked in SSNA (97
      +/- 3 and 91 +/- 5 %, respectively). For each sinusoidal cycle, there were two
      peaks of modulation-one associated with acceleration as the platform moved
      forward or to the side and one associated with acceleration in the opposite
      direction. We believe the two peaks reflect inertial displacement of the
      stereocilia within the utricle during sinusoidal acceleration, which evokes
      vestibulosympathetic reflexes that are expressed as vestibular modulation of MSNA
      as well as of SSNA. The smaller vestibular modulation of MSNA can be explained by
      the dominant modulation of MSNA by the arterial baroreceptors.

PMID- 23852324
TI  - Recruitment of ipsilateral and contralateral upper limb muscles following
      stimulation of the cortical motor areas in the monkey.
AB  - It is well established that cortical motor stimulation results in contralateral
      upper limb (UL) activity. Motor responses are also elicited in the ipsilateral
      UL, though controversy surrounds the significance of these effects. Evidence
      suggests that ipsilateral muscle activity is more common following the
      stimulation of the supplementary motor area (SMA) and dorsal premotor area (PMd),
      compared to the primary motor cortex (M1), but none of these studies compared
      effects from all three areas in the same subjects. This has limited our
      understanding of how these three cortical motor areas influence ipsilateral UL
      muscle activity. The purpose of this study was to determine the contribution of
      each of three cortical areas to the production of ipsilateral and contralateral
      UL. To maximize sensitivity and allow comparison of the effects across cortical
      areas, we applied the same stimulation parameters (36 pulse stimulus train at 330
      Hz) to M1, SMA, and PMd in three adult M. fascicularis and recorded
      electromyographic (EMG) activity from muscles in the trunk and both ULs. Of all
      muscle responses identified, 24 % were ipsilateral to the stimulation, mostly in
      proximal muscles. The highest percentage of ipsilateral responses occurred
      following SMA stimulation. We also observed that PMd stimulation elicited more
      suppression responses compared with stimulation of M1 and SMA. The results
      indicate that ipsilateral motor areas provide a significant contribution to
      cortical activation of the trunk and proximal UL muscles. These understudied
      pathways may represent a functional substrate for future strategies to shape UL
      recovery following injury or stroke.

PMID- 23852326
TI  - Heating efficiency of multi-walled carbon nanotubes in the first and second
      biological windows.
AB  - Quantum dot based-thermometry, in combination with double beam confocal
      microscopy and infrared thermal imaging, has been used to investigate the heating
      efficiency of multi-walled carbon nanotubes (MWCNTs) under optical excitation
      within the first (808 nm) and second (1090 nm) biological windows as well as in
      the spectral region separating them (980 nm). It has been found that for the
      three excitation wavelengths the heating efficiency of MWCNTs (10 nm in diameter
      and 1.5 MUm in length) is close to 50%. Despite this "flat" heating efficiency,
      we have found that the excitation wavelength is, indeed, critical during in vivo
      experiments due to the spectral dependence of both tissue absorption and
      scattering coefficients. It has been concluded that efficiency and selectivity of
      in vivo photothermal treatments based on MWCNTs are simultaneously optimized when
      laser irradiation lies within the first or second biological window. 

PMID- 23852325
TI  - Effects of aging on force coordination in bimanual task performance.
AB  - We investigated within- and between-hands grip-load force coordination in both
      healthy young and older adult participants during bimanual tasks involving
      realistic actions. Age-related changes in manual behaviors such as grip force
      production and safety margins were expected in older adults. Within-hand grip
      load coordination was expected to decrease with aging during the performance of
      dynamic actions, but not static actions. The effects of task and hand dominance
      on task performance were also evaluated. Grip force production increased with
      age; however, changes in fingertip frictional properties with aging increased the
      risk of object slip. Indices of within-hand grip-load coordination did not alter
      with age, but such indices were affected by task goals. The action of connecting
      two independent objects, particularly with rotational action, was associated with
      declines in all indices of within- and between-hands force coordination,
      independent of age. Evidence of task-specific differences in within-hand grip
      load coordination in the current data set suggests that individual hand
      specification emerges and persists with age in everyday bimanual prehension
      tasks, independent of the action role assigned to the dominant and non-dominant
      hands. 

PMID- 23852327
TI  - Gender differences in adapting driving behavior to accommodate visual health
      limitations.
AB  - This study investigated whether men and women are equally likely to adapt their
      driving behaviors in response to visual limitations. Participants were 376 (222
      women and 154 men) pre-surgical cataract patients from the Shiley Eye Center in
      La Jolla, California. All participants completed the National Eye Institute
      Visual Functioning Questionnaire, which assesses self-reported visual symptoms,
      functional limitations, and behaviors including driving during the day, at night,
      or in difficult conditions. Visual acuity was assessed using the log of the
      minimal angle of resolution (LogMAR) scale. There were no significant differences
      in LogMAR visual acuity between men and women who reported either that they
      stopped driving at night because of visual impairment or reported having no
      difficulty driving at night. Of participants who reported having difficulty
      driving at night, mean weighted LogMAR scores indicated significantly better
      visual acuity for women than men. There were no significant differences in LogMAR
      visual acuity between women and men in any of the difficult driving condition
      categories. Significantly more women than men reported that they stopped driving
      in difficult conditions because of eyesight, despite the lack of gender
      differences in visual acuity for this sample. We found no evidence that cataract
      disease had different effects on the visual acuity of older adult men and women.
      However, there was a significant difference between genders in self-reported
      driving behavior. It is possible that some women are more cautious or have less
      need to drive. However, failing to adapt driving behaviors to accommodate visual
      limitations may represent a potential behavioral public health risk for men. 

PMID- 23852328
TI  - Food insecure families: description of access and barriers to food from one
      pediatric primary care center.
AB  - Despite evidence that food insecurity negatively impacts child health, health
      care providers play little role in addressing the issue. To inform potential
      primary care interventions, we sought to assess a range of challenges faced by
      food insecure (FI) families coming to an urban, pediatric primary care setting. A
      cross-sectional study was performed at a hospital-based, urban, academic
      pediatric primary care clinic that serves as a medical home for approximately
      15,000 patients with 35,000 annual visits. Subjects included a convenience sample
      of caregivers of children presenting for either well child or ill care over a 4
      months period in 2012. A self-administered survey assessed household food
      security status, shopping habits, transportation access, budgeting priorities,
      and perceptions about nutrition access in one's community. Bivariate analyses
      between food security status and these characteristics were performed using Chi
      square statistics or Fisher's exact test. The survey was completed by 199
      caregivers. Approximately 33% of families were FI; 93% received food-related
      governmental assistance. FI families were more likely to obtain food from a
      corner/convenience store, utilize food banks, require transportation other than a
      household car, and prioritize paying bills before purchasing food. FI families
      perceived less access to healthy, affordable foods within their community. Thus,
      FI families may face unique barriers to accessing food. Knowledge of these
      barriers could allow clinicians to tailor in-clinic screening and create family
      centered interventions.

PMID- 23852329
TI  - Whole mitochondrial genome sequencing and transcriptional analysis to uncover an
      RT102-type cytoplasmic male sterility-associated candidate Gene Derived from
      Oryza rufipogon.
AB  - Cytoplasmic male sterility (CMS) is a maternally inherited trait in which plants
      fail to produce functional pollen and is associated with the expression of a
      novel open reading frame (orf) gene encoded by the mitochondrial genome. An
      RT102A CMS line and an RT102C fertility restorer line were obtained by successive
      backcrossing between Oryza rufipogon W1125 and O. sativa Taichung 65. Using next
      generation pyrosequencing, we determined whole-genome sequences of the
      mitochondria in RT102-CMS cytoplasm. To identify candidates for the CMS
      associated gene in RT102 mitochondria, we screened the mitochondrial genome for
      the presence of specific orf genes that were chimeric or whose products carried
      predicted transmembrane domains. One of these orf genes, orf352, which showed
      different transcript sizes depending on whether the restorer of fertility (Rf)
      gene was present or not, was identified. The orf352 gene was co-transcribed with
      the ribosomal protein gene rpl5, and the 2.8 kb rpl5-orf352 transcripts were
      processed into 2.6 kb transcripts with a cleavage at the inside of the orf352
      coding region in the presence of the Rf gene. The orf352 gene is an excellent
      candidate for the CMS-associated gene for RT102-CMS.

PMID- 23852330
TI  - Polyspecific organic cation transporters and their biomedical relevance in
      kidney.
AB  - PURPOSE OF REVIEW: Secretion and reabsorption of organic cations in kidney is
      mediated by polyspecific transporters with broadly overlapping substrate
      specificity. Knowledge concerning function, transported compounds, clinical
      impact of mutations in the transporters and drug-drug interactions is rapidly
      increasing. Recent research concerning properties of these transporters and their
      clinical significance for nephrology is summarized. RECENT FINDINGS: Recent data
      showed that the organic cation transporters OCT1-3 form homo-oligomers, and that
      oligomerization is important for transporter targeting to the plasma membrane. A
      functional relevant substrate binding hinge domain in these transporters has been
      identified. Screening of 900 prescription drugs for interaction with the H
      organic cation transporter hMATE1 indicated that 10% of the drugs are inhibitors
      and that 0.5% are effective under clinical conditions. The pivotal role of hOCT2
      for renal secretion of creatinine and metformin was confirmed in clinical
      studies. SUMMARY: Organic cation transporters of the transporter families SLC22
      and SLC47 are critically involved in the renal secretion of various cationic
      drugs. Drug-drug interactions at the transporter level and mutations in the
      transporters lead to changes in pharmacokinetics and influence nephrotoxicity of
      drugs. Further studies are required to improve drug therapies.

PMID- 23852331
TI  - Urate transporters in the genomic era.
AB  - PURPOSE OF REVIEW: Recent advances in genome technology have provided us with a
      list of molecules affecting urate handling in humans, many of which are unlikely
      to be identified through traditional physiological approach alone. Although this
      article is focused on urate, this can be viewed as a successful model of genomics
      physiology collaboration. RECENT FINDINGS: URATv1/GLUT9 (SLC2A9) is shown to play
      a critical role in urate reabsorption at the proximal tubule, probably more
      prominent than its partner URAT1 (SLC22A12). The major site of action of ABCG2
      (ABCG2), an influential urate secretion transporter, has been shown to be the
      intestine rather than the kidney proximal tubule. Accordingly, hypofunction of
      ABCG2 leads to increased fractional excretion of urate, a finding traditionally
      interpreted as overproduction hyperuricemia. Some SLC17 family members secrete
      urate in the kidney or intestine. OAT2 (SLC22A7) may take up urate from blood to
      the proximal tubular cell. In addition, how a common single-nucleotide
      polymorphisms in ABCG2 affects its function has been elucidated. SUMMARY: A finer
      grained picture of urate handling in the human body is now emerging, which will
      help choosing novel targets for urate-lowering therapy.

PMID- 23852332
TI  - New insights into regulated aquaporin-2 function.
AB  - PURPOSE OF REVIEW: Aquaporin-2 (AQP2) water channels in principal cells of the
      kidney collecting duct are essential for urine concentration. Due to application
      of modern technologies, progress in our understanding of AQP2 has accelerated in
      recent years. In this article, we highlight some of the new insights into AQP2
      function that have developed recently, with particular focus on the cell
      biological aspects of AQP2 regulation. RECENT FINDINGS: AQP2 is subjected to a
      number of regulated modifications, including phosphorylation and ubiquitination,
      which are important for AQP2 function, cellular localization and degradation.
      AQP2 is likely internalized via clathrin and non-clathrin-mediated endocytosis.
      Regulation of AQP2 endocytosis, in addition to exocytosis, is a vital mechanism
      in determining overall AQP2 membrane abundance. AQP2 is associated with regulated
      membrane microdomains. Studies using membrane cholesterol depleting reagents, for
      example statins, have supported the role of membrane rafts in regulation of AQP2
      trafficking. Noncanonical roles for AQP2, for example in epithelial cell
      migration, are emerging. SUMMARY: AQP2 function and thus urine concentration is
      dependent on a variety of cell signalling mechanisms, posttranslational
      modification and interplay between AQP2 and its lipid environment. This
      complexity of regulation allows fine-tuning of AQP2 function and thus body water
      homeostasis.

PMID- 23852333
TI  - Diversity of metabolic syndrome criteria in association with cardiovascular
      diseases--a family medicine-based investigation.
AB  - BACKGROUND: This study compared the association between the 3 definitions of
      metabolic syndrome (MetS) suggested by the World Health Organization (WHO),
      National Cholesterol Education Programme (NCEP ATP III), and International
      Diabetes Federation (IDF), and the risk of cardiovascular diseases (CVD) and
      shows the prevalence and characteristics of persons with MetS in continental vs.
      coastal regions and rural vs. urban residence in Croatia. MATERIAL/METHODS: A
      prospective multicenter study was conducted on 3245 participants>=40 years, who
      visited general practices from May to July 2008 for any reason. This was a cross
      sectional study of the Cardiovascular Risk and Intervention Study in Croatia
      family medicine project (ISRCTN31857696). RESULTS: All analyzed MetS definitions
      showed an association with CVD, but the strongest was shown by NCEP ATP III;
      coronary disease OR 2.48 (95% CI 1.80-3.82), cerebrovascular disease OR 2.14
      (1.19-3.86), and peripheral artery disease OR 1.55 (1.04-2.32), especially for
      age and male sex. According to the NCEP ATP III (IDF), the prevalence was 38.7%
      (45.9%) [15.9% (18.6%) in men, and 22.7% (27.3%) in women, and 28.4% (33.9%) in
      the continental region, 10.2% (10.9%) in the coastal region, 26.2% (31.5%) in
      urban areas, and 12.4% (14.4%) in rural areas. Older age, male sex, and residence
      in the continental area were positively associated with MetS diagnosis according
      to NCEP ATP III, and current smoking and Mediterranean diet adherence have
      protective effects. CONCLUSIONS: The NCEP ATP III definition seems to provide the
      strongest association with CVD and should therefore be preferred for use in this
      population.

PMID- 23852334
TI  - Moral injury: a mechanism for war-related psychological trauma in military family
      members.
AB  - Recent research has provided compelling evidence of mental health problems in
      military spouses and children, including post-traumatic stress disorder (PTSD),
      related to the war-zone deployments, combat exposures, and post-deployment mental
      health symptoms experienced by military service members in the family. One
      obstacle to further research and federal programs targeting the psychological
      health of military family members has been the lack of a clear, compelling, and
      testable model to explain how war-zone events can result in psychological trauma
      in military spouses and children. In this article, we propose a possible
      mechanism for deployment-related psychological trauma in military spouses and
      children based on the concept of moral injury, a model that has been developed to
      better understand how service members and veterans may develop PTSD and other
      serious mental and behavioral problems in the wake of war-zone events that
      inflict damage to moral belief systems rather by threatening personal life and
      safety. After describing means of adapting the moral injury model to family
      systems, we discuss the clinical implications of moral injury, and describe a
      model for its psychological treatment. 

PMID- 23852335
TI  - Implementation and dissemination of military informed and evidence-based
      interventions for community dwelling military families.
AB  - Community dwelling military families from the National Guard and Reserve contend
      with deployment-related stressors in relative isolation, living in communities
      where mental health providers may have little knowledge of military culture. When
      they are community residents, active duty service members and families tend to
      live in close proximity to their military installations. This article will focus
      primarily on the challenges to quality mental health care for reserve component
      (RC) families. Where studies of RC families are absent, those of active component
      (AC) families will be highlighted as relevant. Upon completion of a deployment,
      reintegration for RC families is complicated by high rates of symptomatology, low
      service utilization, and greater barriers to care relative to AC families. A
      paucity of providers skilled in evidence-based treatments (EBTs) limits community
      mental health capacity to serve RC military families. Several emergent programs
      illustrate the potential for better serving community dwelling military families.
      Approaches include behavioral health homes, EBTs and treatment components,
      structured resiliency and parent training, military informed schools, outreach
      methods, and technology-based coping, and psychoeducation. Methods from
      implementation science to improve clinical skill acquisition and spread and
      sustainability of EBTs may advance access to and quality of mental health
      treatment and are reviewed herein. Recommendations related to research methods,
      military knowledge and treatment competencies, and transition to a public health
      model of service delivery are discussed. 

PMID- 23852336
TI  - FGF23 and mineral metabolism in the early post-renal transplantation period.
AB  - BACKGROUND: The relationship between fibroblast growth factor 23 (FGF23) and
      vitamin D production and catabolism post-renal transplantation has not been
      characterized. METHODS: Circulating creatinine, calcium, phosphorus, albumin,
      parathyroid hormone, FGF23, and 1,25(OH)2 vitamin D (calcitriol) values were
      obtained pre-transplantation, daily post-operatively for 5 days, and at 6 months
      post-transplantation in 44 patients aged 16.4 +/- 0.4 years undergoing renal
      transplantation at UCLA from 1 August 2005 through to 30 April 2007. 25(OH)
      Vitamin D and 24,25(OH)2 vitamin D concentrations were obtained at baseline and
      on post-operative days 5 and 180, and urinary concentrations of creatinine,
      phosphorus, and FGF23 were measured on post-operative days 1, 3, 5, and 180.
      RESULTS: Circulating phosphate concentrations declined more rapidly and the
      fractional excretion of phosphorus was higher in the first week post
      transplantation in subjects with higher FGF23 values. Fractional excretion of
      FGF23 was low at all time-points. Circulating 1,25(OH)2 vitamin D levels rose
      more rapidly and were consistently higher in patients with lower FGF23 values;
      however, 25(OH) vitamin D and 24,25(OH)2 vitamin D values were unrelated to FGF23
      concentrations. CONCLUSIONS: Inhibition of renal 1alpha-hydroxylase, rather than
      stimulation of 24-hydroxylase, may primarily contribute to the relationship
      between FGF23 values and calcitriol. The rapid decline in FGF23 levels post
      transplantation in our patient cohort was not mediated solely by the filtration
      of intact FGF23 by the new kidney.

PMID- 23852338
TI  - A DFT study on the [VO]1+-ZSM-5 cluster: direct methanol oxidation to
      formaldehyde by N2O.
AB  - The mechanism of direct oxidation of methanol to formaldehyde by N2O has been
      theoretically investigated by means of density functional theory over an extra
      framework species in ZSM-5 zeolite represented by a [(SiH3)4AlO4](1-)[V-O](1+)
      cluster model. The catalytic reactivity of these species is compared with that of
      mononuclear (Fe-O)(1+) sites in ZSM-5 investigated in our earlier work at the
      same level of theory (J. Catal. 2011, 282, 191). The [V-O](1+) site in ZSM-5
      zeolite shows an enhanced catalytic activity for the reaction. The calculated
      vibrational frequencies for grafted species on vanadium sites on the surface are
      in good agreement with the experimental values. According to the theoretical
      results obtained in this study the [V-O](1+) site in the ZSM-5 catalyst has an
      important role in the direct catalytic oxidation of methanol to formaldehyde by
      N2O. 

PMID- 23852337
TI  - Making sense of the spectrum of glomerular disease associated with complement
      dysregulation.
AB  - Over recent years, complement has emerged as a major player in the development of
      a number of glomerular diseases, including atypical haemolytic uraemic syndrome,
      membranoproliferative glomerulonephritis and the recently described C3
      glomerulonephritis. Some patients and pedigrees show overlapping features of
      these conditions. Intriguingly, a few complement gene mutations are common to
      different disease phenotypes. In this review, we explore the evidence for
      complement dysregulation in these diseases and the clinical interface between
      them, and present a hypothesis to explain the variable phenotype associated with
      dysregulation of the alternative complement pathway. 

PMID- 23852339
TI  - Rev-erb-alpha modulates skeletal muscle oxidative capacity by regulating
      mitochondrial biogenesis and autophagy.
AB  - The nuclear receptor Rev-erb-alpha modulates hepatic lipid and glucose
      metabolism, adipogenesis and the inflammatory response in macrophages. We show
      here that Rev-erb-alpha is highly expressed in oxidative skeletal muscle and that
      its deficiency in muscle leads to reduced mitochondrial content and oxidative
      function, as well as upregulation of autophagy. These cellular effects resulted
      in both impaired mitochondrial biogenesis and increased clearance of this
      organelle, leading to compromised exercise capacity. On a molecular level, Rev
      erb-alpha deficiency resulted in deactivation of the Lkb1-Ampk-Sirt1-Ppargc
      1alpha signaling pathway. These effects were recapitulated in isolated fibers and
      in muscle cells after knockdown of the gene encoding Rev-erb-alpha, Nr1d1. In
      complementary experiments, Rev-erb-alpha overexpression in vitro increased the
      number of mitochondria and improved respiratory capacity, whereas muscle
      overexpression or pharmacological activation of Rev-erb-alpha in vivo increased
      exercise capacity. This study identifies Rev-erb-alpha as a pharmacological
      target that improves muscle oxidative function by modulating gene networks
      controlling mitochondrial number and function. 

PMID- 23852340
TI  - Suppressing aberrant GluN3A expression rescues synaptic and behavioral
      impairments in Huntington's disease models.
AB  - Huntington's disease is caused by an expanded polyglutamine repeat in the
      huntingtin protein (HTT), but the pathophysiological sequence of events that
      trigger synaptic failure and neuronal loss are not fully understood. Alterations
      in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been
      implicated. Yet, it remains unclear how the HTT mutation affects NMDAR function,
      and direct evidence for a causative role is missing. Here we show that mutant HTT
      redirects an intracellular store of juvenile NMDARs containing GluN3A subunits to
      the surface of striatal neurons by sequestering and disrupting the subcellular
      localization of the endocytic adaptor PACSIN1, which is specific for GluN3A.
      Overexpressing GluN3A in wild-type mouse striatum mimicked the synapse loss
      observed in Huntington's disease mouse models, whereas genetic deletion of GluN3A
      prevented synapse degeneration, ameliorated motor and cognitive decline and
      reduced striatal atrophy and neuronal loss in the YAC128 Huntington's disease
      mouse model. Furthermore, GluN3A deletion corrected the abnormally enhanced NMDAR
      currents, which have been linked to cell death in Huntington's disease and other
      neurodegenerative conditions. Our findings reveal an early pathogenic role of
      GluN3A dysregulation in Huntington's disease and suggest that therapies targeting
      GluN3A or pathogenic HTT-PACSIN1 interactions might prevent or delay disease
      progression. 

PMID- 23852342
TI  - The genome of a baculovirus isolated from Hemileuca sp. encodes a serpin
      ortholog.
AB  - The genome sequence of a baculovirus from Hemileuca sp. was determined. The
      genome is 140,633 kb, has a G+C content of 38.1 %, and encodes 137 putative open
      reading frames over 50 amino acids. 126 of these ORFs showed similarity to other
      baculovirus genes in the database including all 37 core genes. Of the remaining
      11 predicted genes, one is related to a lepidopteran serpin gene. This is the
      first report of a baculovirus encoding a member of this family of serine protease
      inhibitors, and to our knowledge the first report of a viral serpin outside the
      Poxviridae. The genome also contained three homologous repeat sequences.
      Phylogenetic analysis indicated that the virus is a group II Alphabaculovirus and
      belongs to a lineage that includes Orgyia leucostigma, Ectropis obliqua,
      Apocheima cinerarium, and Euproctis pseudoconspersa nucleopolyhedroviruses. 

PMID- 23852341
TI  - BACH2 mediates negative selection and p53-dependent tumor suppression at the pre
      B cell receptor checkpoint.
AB  - The B cell-specific transcription factor BACH2 is required for affinity
      maturation of B cells. Here we show that Bach2-mediated activation of p53 is
      required for stringent elimination of pre-B cells that failed to productively
      rearrange immunoglobulin VH-DJH gene segments. After productive VH-DJH gene
      rearrangement, pre-B cell receptor signaling ends BACH2-mediated negative
      selection through B cell lymphoma 6 (BCL6)-mediated repression of p53. In
      patients with pre-B acute lymphoblastic leukemia, the BACH2-mediated checkpoint
      control is compromised by deletions, rare somatic mutations and loss of its
      upstream activator, PAX5. Low levels of BACH2 expression in these patients
      represent a strong independent predictor of poor clinical outcome. In this study,
      we demonstrate that Bach2(+/+) pre-B cells resist leukemic transformation by Myc
      through Bach2-dependent upregulation of p53 and do not initiate fatal leukemia in
      transplant-recipient mice. Chromatin immunoprecipitation sequencing and gene
      expression analyses carried out by us revealed that BACH2 competes with BCL6 for
      promoter binding and reverses BCL6-mediated repression of p53 and other cell
      cycle checkpoint-control genes. These findings identify BACH2 as a crucial
      mediator of negative selection at the pre-B cell receptor checkpoint and a
      safeguard against leukemogenesis. 

PMID- 23852343
TI  - Metabolic glycoengineering of Staphylococcus aureus reduces its adherence to
      human T24 bladder carcinoma cells.
AB  - The Gram-positive bacterium Staphylococcus aureus is a human pathogen
      increasingly causing severe infections, especially in hospital environments.
      Moreover, strains which are resistant against various types of antibiotics are
      developing and spreading widely as in the case of the community-acquired MRSA
      (methicillin resistant S. aureus). In this study metabolic glycoengineering with
      N-azidoacetyl-glucosamine (GlcNAz) has been successfully applied to S. aureus for
      the first time. The following bioorthogonal Mendal-Sharpless-Huisgen click
      reaction between the azido-functionalized S. aureus cells and alkyne dyes enabled
      staining of these bacteria and reduced their adherence to human T24 bladder
      carcinoma cells by 48%. The results are of urgent interest to study S. aureus
      infections. 

PMID- 23852344
TI  - Daily variations in plasma melatonin and melatonin receptor (MT1), PER1 and CRY1
      expression in suprachiasmatic nuclei of tropical squirrel, Funambulus pennanti.
AB  - The suprachiasmatic nucleus (SCN) plays a major role in photoperiodic regulation
      of seasonal functions by modulating the melatonin signal. To date no report
      exists regarding the role of the ambient photoperiod in the regulation of
      melatonin receptor MT1 and clock gene (PER1 and CRY1) expression in the SCN of
      any tropical rodent that experiences the least variation in the photoperiod. We
      noted the expression of MT1, PER1 and CRY1 in the SCN of a tropical squirrel,
      Funambulus pennanti, along with the plasma level of melatonin over 24 h during
      the reproductively active (summer) and inactive (winter) phases. The seasonal day
      length affected the peripheral melatonin, which was inversely related with the
      MT1 expression in the SCN. The timing for peak expression of PER1 was the same in
      both phases, while the decline in PER1 expression was delayed by 4 h during the
      inactive phase. The CRY1 peak advanced by 4 h during the active phase, while the
      interval between the peak and decline of CRY1 remained the same in both phases.
      It can be suggested that seasonally changing melatonin levels modulate MT1
      expression dynamics in the SCN, altering its functional state, and gate SCN
      molecular "clock" gene profiles through changes in PER/CRY expression. Such a
      regulation is important for photo-physiological adaptation
      (reproduction/immunity) in seasonal breeders. 

PMID- 23852346
TI  - Brace yourself! Leaving your comfort zone.

PMID- 23852347
TI  - Will you be ready when disaster strikes?

PMID- 23852345
TI  - Fetal echocardiography and pulsed-wave Doppler ultrasound in a rabbit model of
      intrauterine growth restriction.
AB  - Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function
      that is apparent antenatally due to advances in fetoplacental Doppler ultrasound
      and fetal echocardiography. Increasingly, these imaging modalities are being
      employed clinically to examine cardiac function and assess wellbeing in utero,
      thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR
      that allows analysis of cardiac function in a clinically relevant way. Using
      isoflurane induced anesthesia, IUGR is surgically created at gestational age day
      25 by performing a laparotomy, exposing the bicornuate uterus and then ligating
      40-50% of uteroplacental vessels supplying each gestational sac in a single
      uterine horn. The other horn in the rabbit bicornuate uterus serves as internal
      control fetuses. Then, after recovery at gestational age day 30 (full term), the
      same rabbit undergoes examination of fetal cardiac function. Anesthesia is
      induced with ketamine and xylazine intramuscularly, then maintained by a
      continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic
      effects on fetal cardiac function. A repeat laparotomy is performed to expose
      each gestational sac and a microultrasound examination (VisualSonics VEVO 2100)
      of fetal cardiac function is performed. Placental insufficiency is evident by a
      raised pulsatility index or an absent or reversed end diastolic flow of the
      umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery
      Doppler is then examined. Fetal echocardiography is performed by recording B
      mode, M mode and flow velocity waveforms in lateral and apical views. Offline
      calculations determine standard M-mode cardiac variables, tricuspid and mitral
      annular plane systolic excursion, speckle tracking and strain analysis, modified
      myocardial performance index and vascular flow velocity waveforms of interest.
      This small animal model of IUGR therefore affords examination of in utero cardiac
      function that is consistent with current clinical practice and is therefore
      useful in a translational research setting. 

PMID- 23852348
TI  - Idiopathic intracranial hypertension in a patient with thyroid papillary
      carcinoma.

PMID- 23852349
TI  - When can plant-pollinator interactions promote plant diversity?
AB  - In the light of rapid losses of biodiversity worldwide, it has become more
      important than ever to study the factors that ensure the continued existence of
      diverse ecological communities. Whereas the diversity-enhancing effects of
      antagonistic interactions are relatively well understood, much less is known
      about the contribution of mutualistic interactions to biodiversity maintenance.
      This study assesses the influence of mutualistic interactions with pollinators on
      the diversity of plant communities with alternative means of reproduction besides
      animal pollination. In contrast to a recent more general model of plant-animal
      mutualisms, the results of our simulations suggest that interactions with
      pollinators do not generally promote plant diversity, irrespective of the
      structure of the interaction network. Despite a potential for increased plant
      species richness through the positive effect of pollinators on plant birth rates,
      species richness was mostly negatively affected by the presence of pollinators
      because existing abundance asymmetries were amplified by animal pollination. Our
      results imply that for plant communities with alternative means of reproduction,
      the loss of pollinators will usually not lead to decreased diversity. However,
      whereas the immediate effects of pollinator loss on plant community composition
      may be negligible, the long-term population genetic consequences are likely to be
      severe.

PMID- 23852350
TI  - Disentangling direct and indirect fitness effects of microbial dormancy.
AB  - Disentangling individual selection from kin selection is one of the greatest
      challenges of evolutionary biology. Even solitary organisms that do not interact
      directly with conspecifics may interact indirectly with them through competition
      for resources. As a result, traits that appear to affect individual fitness alone
      can also modify the fitness of relatives nearby and thus may evolve partially
      through these cryptic indirect fitness effects. Here we develop a method to
      quantitatively separate direct and indirect fitness consequences when some
      microbes become dormant, while neighbors of the same genotype remain active.
      Dormant microbes typically survive stresses that kill metabolically active cells,
      but dormancy also has a social side effect, sparing resources that may be used by
      nondormant individuals for growth. In structured populations, spared resources
      may be preferentially consumed by nondormant clonemates, providing an indirect
      benefit. Without population structure, however, exploitation by a never-dormant
      competitor imposes an indirect fitness cost on dormant cells. Cryptic indirect
      fitness effects may play a significant role in the evolution of many ostensibly
      asocial traits.

PMID- 23852351
TI  - Heterospecific aggression and dominance in a guild of coral-feeding fishes: the
      roles of dietary ecology and phylogeny.
AB  - Interspecific competition mediates biodiversity maintenance and is an important
      selective pressure for evolution. Competition is often conceptualized as being
      exploitative (indirect) or involving direct interference. However, most empirical
      studies are phenomenological, focusing on quantifying effects of density
      manipulations, and most competition theory has characterized exploitation
      competition systems. The effects on resource use of traits associated with
      direct, interference competition has received far less attention. Here we examine
      the relationships of dietary ecology and phylogeny to heterospecific aggression
      in a guild of corallivorous reef fishes. We find that, among chaetodontids
      (butterflyfishes), heterospecific aggression depends on a synergistic interaction
      of dietary overlap and specialization: aggression increases with dietary overlap
      for interactions between specialists but not for interactions involving
      generalists. Moreover, behavioral dominance is a monotonically increasing
      function of dietary specialization. The strong, positive relationship of
      dominance to specialization suggests that heterospecific aggression may
      contribute to the maintenance of biodiversity where it promotes resource
      partitioning. Additionally, we find strong phylogenetic signals in dietary
      overlap and specialization but not behavioral dominance. Our results support the
      use of phylogeny as a proxy for ecological similarity among butterflyfishes, but
      we find that direct measures of dietary overlap and specialization predict
      heterospecific agression much better than phylogeny.

PMID- 23852352
TI  - Spatial variability in plant predation determines the strength of stochastic
      community assembly.
AB  - High diversity is often poorly explained by trait-based deterministic models, in
      part because stochastic processes also influence community assembly. Testing how
      deterministic and stochastic processes combine to regulate diversity, however,
      has been limited by the spatial complexity of these interactions. Here, we
      demonstrate how spatial variability in small-mammal predation on plants, mostly
      by granivory, results in fine-scale switching between deterministically and
      stochastically regulated plant community assembly in an otherwise environmentally
      homogeneous tallgrass prairie. We initiated assembly with the uniform application
      of a 24-species mixture of prairie grasses and forbs, thereby setting the maximum
      level of diversity (gamma-diversity). In field edges with higher densities of
      small mammals, traits reducing seed palatability deterministically produced
      homogeneous subsets of less palatable plant species within the first few months
      after planting (low alpha and beta diversity). As small-mammal densities
      decreased in more open areas, assembly unfolded stochastically on the basis of
      which planted species happened to land at a given location (high alpha and beta
      diversity). We used randomization models to validate that this higher beta
      diversity was explained by true differences in community structure among plots
      rather than by the hidden effects of increasing alpha diversity. The net effect
      at the site level was a spatially structured array of prairie species, including
      a positive relationship between diversity and environmental suitability relating
      to reduced predator intensity.

PMID- 23852353
TI  - Disturbance frequency and vertical distribution of seeds affect long-term
      population dynamics: a mechanistic seed bank model.
AB  - Seed banks are critically important for disturbance specialist plants because
      seeds of these species germinate only in disturbed soil. Disturbance and seed
      depth affect the survival and germination probability of seeds in the seed bank,
      which in turn affect population dynamics. We develop a density-dependent
      stochastic integral projection model to evaluate the effect of stochastic soil
      disturbances on plant population dynamics with an emphasis on mimicking how
      disturbances vertically redistribute seeds within the seed bank. We perform a
      simulation analysis of the effect of the frequency and mean depth of disturbances
      on the population's quasi-extinction probability, as well as the long-term mean
      and variance of the total density of seeds in the seed bank. We show that
      increasing the frequency of disturbances increases the long-term viability of the
      population, but the relationship between the mean depth of disturbance and the
      long-term viability of the population are not necessarily monotonic for all
      parameter combinations. Specifically, an increase in the probability of
      disturbance increases the long-term viability of the total seed bank population.
      However, if the probability of disturbance is too low, a shallower mean depth of
      disturbance can increase long-term viability, a relationship that switches as the
      probability of disturbance increases. However, a shallow disturbance depth is
      beneficial only in scenarios with low survival in the seed bank.

PMID- 23852354
TI  - Phenotypic selection favors missing trait combinations in coexisting annual
      plants.
AB  - Trade-offs among traits are important for maintaining biodiversity, but the role
      of natural selection in their construction is not often known. It is possible
      that trade-offs reflect fundamental constraints, negative correlational
      selection, or directional selection operating on costly, redundant traits. In a
      Sonoran Desert community of winter annual plants, we have identified a trade-off
      between relative growth rate and water-use efficiency among species, such that
      species with high relative growth rate have low water-use efficiency and vice
      versa. We measured selection on water-use efficiency, relative growth rate, and
      underlying traits within populations of four species at two study sites with
      different average climates. Phenotypic trait correlations within species did not
      match the among-species trade-off. In fact, for two species with high water-use
      efficiency, individuals with high relative growth rate also had high water-use
      efficiency. All populations experienced positive directional selection for water
      use efficiency and relative growth rate. Selection tended to be stronger on water
      use efficiency at the warmer and drier site, and selection on relative growth
      rate tended to be stronger at the cooler and wetter site. Our results indicate
      that directional natural selection favors a phenotype not observed among species
      in the community, suggesting that the among-species trade-off could be due to
      pervasive genetic constraints, perhaps acting in concert with processes of
      community assembly.

PMID- 23852355
TI  - Warning signals of regime shifts as intrinsic properties of endogenous dynamics.
AB  - Ecosystem dynamics can exhibit large, nonlinear changes after small changes in an
      environmental parameter that passes a critical threshold. These regime shifts are
      often associated with loss of biodiversity and ecosystem services. Because
      critical thresholds for regime shifts are hard to determine with precision, some
      recent studies have focused on deriving signals from dynamics leading up to the
      thresholds. Models in these studies depend on using noise terms independent of
      system parameters and variables to add stochasticity. However, demographic
      stochasticity, an important source of random variability, arises directly from
      system dynamics. In this study, a framework is developed for modeling demographic
      stochasticity in a mechanistic way, incorporating system variables and
      parameters. This framework is applied to a deterministic, dynamic model of a
      coral reef benthos. The resulting stochastic model indicates that increasing
      variance-but not skewness-is consistently found in system dynamics approaching a
      critical threshold of grazing pressure. Even if the threshold is breached,
      attraction of transient dynamics by a saddle point provides an opportunity for
      regime shift reversal by management intervention. These results suggest that
      early warning signals of regime shifts can arise intrinsically in endogenous
      dynamics and can be detected without reliance on random environmental forcings.

PMID- 23852356
TI  - Stage dependence of phenotypical and phenological maternal effects: insight into
      squamate reptile reproductive strategies.
AB  - Enhanced thermal conditions have been credited as a driving force for the
      evolution of viviparity, particularly in squamate reptiles, among which it has
      independently evolved more than 100 times. However, maternal thermoregulation is
      also a critical component of reproduction in oviparous squamates, for which
      considerable embryonic development occurs prior to oviposition. When carrying
      eggs, oviparous mothers modify thermoregulation in a manner similar to that of
      pregnant females. To further understand the role of temperature in influencing
      reproductive strategies, it is critical that we elucidate the degree to which
      thermal sensitivity varies across developmental stages. We studied stage
      dependent embryonic sensitivity in a viviparous snake, the aspic viper (Vipera
      aspis). We manipulated female body temperature at different stages of pregnancy
      early development, early embryonic growth, and late embryonic growth-by imposing
      two contrasting daily thermal cycles that mimicked reproductive (warm) and
      nonreproductive (cool) female temperature profiles. Thermal sensitivity of
      offspring phenotype was stage dependent, with offspring quality more negatively
      affected when exposure to cool temperatures occurred early in development. In
      contrast, developmental rate was slowed by the cooler cycle, independent of the
      timing of the exposure. Given the more persistent effect on phenology,
      phenological effects likely provide a greater driving force for complete
      embryonic retention (i.e., viviparity).

PMID- 23852357
TI  - A metabolic and body-size scaling framework for parasite within-host abundance,
      biomass, and energy flux.
AB  - Energetics may provide a useful currency for studying the ecology of parasite
      assemblages within individual hosts. Parasite assemblages may also provide
      powerful models to study general principles of ecological energetics. Yet there
      has been little ecological research on parasite-host energetics, probably due to
      methodological difficulties. However, the scaling relationships of individual
      metabolic rate with body or cell size and temperature may permit us to tackle the
      energetics of parasite assemblages in hosts. This article offers the foundations
      and initial testing of a metabolic theory of ecology (MTE) framework for
      parasites in hosts. I first provide equations to estimate energetic flux through
      observed parasite assemblages. I then develop metabolic scaling theory for
      parasite abundance, energetics, and biomass in individual hosts. In contrast to
      previous efforts, the theory factors in both host and parasite metabolic scaling,
      how parasites use host space, and whether energy or space dictates carrying
      capacity. Empirical tests indicate that host energetic flux can set parasite
      carrying capacity, which decreases as predicted considering the scaling of host
      and parasite metabolic rates. The theory and results also highlight that the
      phenomenon of "energetic equivalence" is not an assumption of MTE but a possible
      outcome contingent on how species partition resources. Hence, applying MTE to
      parasites can lend mechanistic, quantitative, predictive insight into the nature
      of parasitism and can inform general ecological theory.

PMID- 23852358
TI  - Vanishing chromosomal inversion clines in Drosophila subobscura from Chile: is
      behavioral thermoregulation to blame?
AB  - Chromosomal inversion clines paralleling the long-standing ones in native
      Palearctic populations of Drosophila subobscura evolved swiftly after this
      species invaded the Americas in the late 1970s and early 1980s. However, the new
      clines did not consistently continue to converge on the Old World baseline. Our
      recent survey of Chilean populations of D. subobscura shows that inversion clines
      have faded or even changed sign with latitude. Here, we investigate the
      hypothesis that this fading of inversion clines might be due to the Bogert
      effect, namely, that flies' thermoregulatory behavior has eventually compensated
      for environmental variation in temperature, thus buffering selection on thermal
      related traits. We show that latitudinal divergence in thermal preference (Tp)
      has evolved in Chile for females, with higher-latitude flies having a lower mean
      Tp. Plastic responses in Tp also lessen latitudinal thermal variation because
      flies developed at colder temperatures prefer warmer microclimates. Our results
      are consistent with the idea that active behavioral thermoregulation might buffer
      environmental variation and reduce the potential effect of thermal selection on
      other traits as chromosomal arrangements.

PMID- 23852359
TI  - Extreme intraclutch egg-size dimorphism in Eudyptes penguins, an evolutionary
      response to clutch-size maladaptation.
AB  - Eudyptes penguins (six species) are uniquely characterized by a two-egg clutch
      with extreme intraclutch egg-size dimorphism (ESD): the first-laid A-egg is 17.5%
      56.9% smaller than the B-egg. Although A-eggs are viable, they almost never
      produce fledged chicks (genus average <1%). Using classical life-history theory
      and phylogenetic comparative methods, we demonstrate a marked slowdown in the
      life history of Eudyptes: age of first reproduction is 52% later and annual
      fecundity 48% lower compared with other two-egg clutch penguin species. All six
      Eudyptes species have retained a two-egg clutch, despite this pronounced life
      history slowdown; this suggests evolutionary mismatch between clutch size and
      chicks fledged per clutch. Consistent with this, we show that Eudyptes fledge 43%
      fewer chicks per clutch than other two-egg clutch penguin species. Extreme
      intraclutch ESD in Eudyptes is associated primarily with a uniform (5%) increase
      in relative B-egg size, and B-egg size has evolved in accord with life history.
      We further show that intraclutch ESD is positively correlated with age of first
      reproduction in Eudyptes but not in other two-egg clutch penguin species. We
      argue that Eudyptes' persistent failure to evolve a one-egg clutch constitutes a
      unique genus-wide evolutionary maladaptation and that extreme intraclutch ESD
      evolved as a correlated response to selection favoring a slower life history
      imposed by their extreme pelagic overwintering and migration ecology.

PMID- 23852360
TI  - Stochastic dispersal and population persistence in marine organisms.
AB  - Temporally variable conditions introduce time dependence into vital rates, and
      predicting the effect of this variability on population dynamics and persistence
      is critical for the effective management of natural populations subject to
      fluctuating environments. In many marine species, dispersal during the larval
      stage establishes links among populations and is largely determined by temporally
      variable fluid dynamic processes. However, the consequences of time-dependent
      dispersal for population persistence are largely unexplored, and so we present a
      model of stochastically driven dispersal to study population persistence in a
      temporally variable, patchy habitat. We illustrate how patterns of temporal
      autocorrelation, expressed as variance in stochastic population connectivity, can
      have counterintuitive consequences for predictions, where switching between two
      sets of dynamics, each of which leads to extinction, can promote metapopulation
      persistence. We contend that accounting for stochastic dispersal can have great
      relevance for understanding population persistence, in marine populations in
      particular and in organisms with some degree of passive dispersal in general.

PMID- 23852361
TI  - Optimal control and cold war dynamics between plant and herbivore.
AB  - Herbivores eat the leaves that a plant needs for photosynthesis. However, the
      degree of antagonism between plant and herbivore may depend critically on the
      timing of their interactions and the intrinsic value of a leaf. We present a
      model that investigates whether and when the timing of plant defense and
      herbivore feeding activity can be optimized by evolution so that their
      interactions can move from antagonistic to neutral. We assume that temporal
      changes in environmental conditions will affect intrinsic leaf value, measured as
      potential carbon gain. Using optimal-control theory, we model herbivore
      evolution, first in response to fixed plant strategies and then under
      coevolutionary dynamics in which the plant also evolves in response to the
      herbivore. In the latter case, we solve for the evolutionarily stable strategies
      of plant defense induction and herbivore hatching rate under different ecological
      conditions. Our results suggest that the optimal strategies for both plant and
      herbivore are to avoid direct conflict. As long as the plant has the capability
      for moderately lethal defense, the herbivore will modify its hatching rate to
      avoid plant defenses, and the plant will never have to use them. Insights from
      this model offer a possible solution to the paradox of sublethal defenses and
      provide a mechanism for stable plant-herbivore interactions without the need for
      natural enemy control.

PMID- 23852362
TI  - Spatial and temporal drivers of phenotypic diversity in polymorphic snakes.
AB  - Color polymorphism in natural populations presents an ideal opportunity to study
      the evolutionary drivers of phenotypic diversity. Systems with striking spatial,
      temporal, and qualitative variation in color can be leveraged to study the
      mechanisms promoting the distribution of different types of variation in nature.
      We used the highly polymorphic ground snake (Sonora semiannulata), a putative
      coral snake mimic with both cryptic and conspicuous morphs, to compare patterns
      of neutral genetic variation and variation over space and time in color
      polymorphism to investigate the mechanistic drivers of phenotypic variation
      across scales. We found that strong selection promotes color polymorphism across
      spatial and temporal scales, with morph frequencies differing markedly between
      juvenile and adult age classes within a single population, oscillating over time
      within multiple populations, and varying drastically over the landscape despite
      minimal population genetic structure. However, we found no evidence that
      conspicuousness of morphs was related to which color pattern was favored by
      selection or to any geographic factors, including sympatry with coral snakes. We
      suggest that complex patterns of phenotypic variation in polymorphic systems may
      be a fundamental outcome of the conspicuousness of morphs and that explicit tests
      of temporal and geographic variation are critical to the interpretation of
      conspicuousness and mimicry.

PMID- 23852363
TI  - Ecology and evolution affect network structure in an intimate marine mutualism.
AB  - Elucidating patterns and causes of interaction among mutualistic species is a
      major focus of ecology, and recent meta-analyses of terrestrial networks show
      that network-level reciprocal specialization tends to be higher in intimate
      mutualisms than in nonintimate mutualisms. It is largely unknown, however,
      whether this pattern holds for and what factors affect specialization in marine
      mutualisms. Here we present the first analysis of network specialization
      ([Formula: see text]) for marine mutualistic networks. Specialization among eight
      Indo-Pacific networks of obligate mutualistic gobies and shrimps was
      indistinguishable from that among comparably intimate terrestrial mutualisms
      (ants-myrmecophytes) and higher than that among nonintimate ones (seed
      dispersers). Specialization was affected by variability in habitat use for both
      gobies and shrimps and by phylogenetic history for shrimps. Habitat use was
      phylogenetically conserved among shrimp, and thus effects of shrimp phylogeny on
      partner choice were mediated in part by habitat. By contrast, habitat use and
      pairing patterns in gobies were not related to phylogenetic history. This
      asymmetry appears to result from evolutionary constraints on partner use in
      shrimps and convergence among distantly related gobies to utilize burrows
      provided by multiple shrimp species. Results indicate that the evolution of
      mutualism is affected by life-history characteristics that transcend environments
      and that different factors constrain interactions in disparate ecosystems.

PMID- 23852365
TI  - Utilizing repetitive transcranial magnetic stimulation to improve language
      function in stroke patients with chronic non-fluent aphasia.
AB  - Transcranial magnetic stimulation (TMS) has been shown to significantly improve
      language function in patients with non-fluent aphasia(1). In this experiment, we
      demonstrate the administration of low-frequency repetitive TMS (rTMS) to an
      optimal stimulation site in the right hemisphere in patients with chronic non
      fluent aphasia. A battery of standardized language measures is administered in
      order to assess baseline performance. Patients are subsequently randomized to
      either receive real rTMS or initial sham stimulation. Patients in the real
      stimulation undergo a site-finding phase, comprised of a series of six rTMS
      sessions administered over five days; stimulation is delivered to a different
      site in the right frontal lobe during each of these sessions. Each site-finding
      session consists of 600 pulses of 1 Hz rTMS, preceded and followed by a picture
      naming task. By comparing the degree of transient change in naming ability
      elicited by stimulation of candidate sites, we are able to locate the area of
      optimal response for each individual patient. We then administer rTMS to this
      site during the treatment phase. During treatment, patients undergo a total of
      ten days of stimulation over the span of two weeks; each session is comprised of
      20 min of 1 Hz rTMS delivered at 90% resting motor threshold. Stimulation is
      paired with an fMRI-naming task on the first and last days of treatment. After
      the treatment phase is complete, the language battery obtained at baseline is
      repeated two and six months following stimulation in order to identify rTMS
      induced changes in performance. The fMRI-naming task is also repeated two and six
      months following treatment. Patients who are randomized to the sham arm of the
      study undergo sham site-finding, sham treatment, fMRI-naming studies, and repeat
      language testing two months after completing sham treatment. Sham patients then
      cross over into the real stimulation arm, completing real site-finding, real
      treatment, fMRI, and two- and six-month post-stimulation language testing. 

PMID- 23852366
TI  - STAT6-mediated BCL6 repression in primary mediastinal B-cell lymphoma (PMBL).
AB  - Primary mediastinal B-cell lymphoma (PMBL) is characterized by aberrant
      activation of JAK/STAT-signaling resulting in constitutive presence of
      phosphorylated STAT6 (pSTAT6). In primary PMBL samples pSTAT6 is only expressed
      in a sub-population of lymphoma cells in a pattern that is reminiscent of that of
      the BCL6 oncogene. Double-fluorescence staining was carried out to determine the
      association between these two proteins in ten primary PMBL cases and three
      available PMBL cell line models. Surprisingly, only a minute fraction of double
      positive nuclei was observed, while each sample contained considerable fractions
      of single-positive pSTAT6 and BCL6 nuclei. The intratumoral coexistence of
      BCL6+/pSTAT6- and BCL6-/pSTAT6+ subpopulations suggests a negative interaction
      between these factors. In silico screening of the STAT6 /BCL6 promoters for DNA
      consensus binding sites identified five STAT-binding-sites in the BCL6 promoter.
      We confirmed STAT6 binding to the BCL6 promoter in vitro and in vivo by band
      shift / super shift assays and chromatin immunoprecipitations. Using BCL6
      luciferase reporter assays, depletion of STAT6 by siRNA, and ectopic
      overexpression of a constitutive active STAT6 mutant, we proved that pSTAT6 is
      sufficient to transcriptionally repress BCL6. Recently developed small molecule
      inhibitors 79-6 and TG101348 that increases BCL6 target gene expression and
      decreases pSTAT6 levels, respectively, demonstrate that a combined targeting
      results in additive efficacy regarding their negative effect on cell viability.
      The delineated pSTAT6-mediated molecular repression mechanism links JAK/STAT to
      BCL6-signaling in PMBL and may carry therapeutic potential. 

PMID- 23852367
TI  - Unravelling suitable graphene-metal contacts for graphene-based plasmonic
      devices.
AB  - Plasmonic excitations in pristine and air-exposed graphene-Ru and graphene-Pt
      contacts have been investigated by using high-resolution electron energy loss
      spectroscopy. Loss measurements show that the effects of air exposure are very
      different in these two systems. While in graphene-Ru contacts, plasmons are
      completely quenched, plasmons in the graphene-Pt interface show only a frequency
      shift together with an overall intensity attenuation. These results pose
      significant questions as regards the stability in an ambient air atmosphere of
      graphene-based plasmonic devices and indicate a suitable choice of graphene-metal
      contacts. 

PMID- 23852368
TI  - Benefits and challenges of electronic health record system on stakeholders: a
      qualitative study of outpatient physicians.
AB  - Electronic health record system (EHRS) is an important healthcare innovation
      associated with many controversies about the benefits and challenges to different
      stakeholders. The aim of this study was to investigate the utility of EHRS by
      outpatient physicians in Macao and to identify, in their opinions, the
      significance of EHRS on health institutes, patients, and physicians. Semi
      structured interviews were conducted with 32 physicians who worked in the
      outpatient department. The interview data showed that 78% physicians interviewed
      used EHRS frequently during their daily practice despite individual preferences
      of documentation methods. They agreed that systemic health record offered by EHRS
      allowing smooth communication was beneficial to the health institutes, patients
      and physicians. However, privacy and confidentiality concerned both the health
      institutes and patients. Inefficiency of the EHRS that only allowed retrieval of
      limited medical information of the patients hindered physicians' acceptability of
      EHRS. It was also suggested that the health institutes should take into
      consideration interests of different stakeholders when designing and implementing
      EHRS.

PMID- 23852369
TI  - MEK drives cyclin D1 hyperelevation during geroconversion.
AB  - When the cell cycle becomes arrested, MTOR (mechanistic Target of Rapamycin)
      converts reversible arrest into senescence (geroconversion). Hyperexpression of
      cyclin D1 is a universal marker of senescence along with hypertrophy, beta-Gal
      staining and loss of replicative/regenerative potential (RP), namely, the ability
      to restart proliferation when the cell cycle is released. Inhibition of MTOR
      decelerates geroconversion, although only partially decreases cyclin D1. Here we
      show that in p21- and p16-induced senescence, inhibitors of mitogen
      activated/extracellular signal-regulated kinase (MEK) (U0126, PD184352 and siRNA)
      completely prevented cyclin D1 accumulation, making it undetectable. We also used
      MEL10 cells in which MEK inhibitors do not inhibit MTOR. In such cells, U0126 by
      itself induced senescence that was remarkably cyclin D1 negative. In contrast,
      inhibition of cyclin-dependent kinase (CDK) 4/6 by PD0332991 caused cyclin D1
      positive senescence in MEL10 cells. Both types of senescence were suppressed by
      rapamycin, converting it into reversible arrest. We confirmed that the inhibitor
      of CDK4/6 caused cyclin D1 positive senescence in normal RPE cells, whereas U0126
      prevented cyclin D1 expression. Elimination of cyclin D1 by siRNA did not prevent
      other markers of senescence that are consistent with the lack of its effect on
      MTOR. Our data confirmed that a mere inhibition of the cell cycle was sufficient
      to cause senescence, providing MTOR was active, and inhibition of MEK partially
      inhibited MTOR in a cell-type-dependent manner. Second, hallmarks of senescence
      may be dissociated, and hyperelevated cyclin D1, a marker of hyperactivation of
      senescent cells, did not necessarily determine other markers of senescence.
      Third, inhibition of MEK was sufficient to eliminate cyclin D1, regardless of
      MTOR. 

PMID- 23852370
TI  - Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress
      in a mouse model of normal tension glaucoma.
AB  - Dedicator of cytokinesis 3 (Dock3), a new member of the guanine nucleotide
      exchange factors for the small GTPase Rac1, promotes axon regeneration following
      optic nerve injury. In the present study, we found that Dock3 directly binds to
      the intracellular C-terminus domain of NR2B, an N-methyl-D-aspartate (NMDA)
      receptor subunit. In transgenic mice overexpressing Dock3 (Dock3 Tg), NR2B
      expression in the retina was significantly decreased and NMDA-induced retinal
      degeneration was ameliorated. In addition, overexpression of Dock3 protected
      retinal ganglion cells (RGCs) from oxidative stress. We previously reported that
      glutamate/aspartate transporter (GLAST) is a major glutamate transporter in the
      retina, and RGC degeneration due to glutamate neurotoxicity and oxidative stress
      is observed in GLAST-deficient (KO) mice. In GLAST KO mice, the NR2B
      phosphorylation rate in the retina was significantly higher compared with Dock3
      Tg:GLAST KO mice. Consistently, glaucomatous retinal degeneration was
      significantly improved in GLAST KO:Dock3 Tg mice compared with GLAST KO mice.
      These results suggest that Dock3 overexpression prevents glaucomatous retinal
      degeneration by suppressing both NR2B-mediated glutamate neurotoxicity and
      oxidative stress, and identifies Dock3 signaling as a potential therapeutic
      target for both neuroprotection and axonal regeneration. 

PMID- 23852371
TI  - Intracellular ASIC1a regulates mitochondrial permeability transition-dependent
      neuronal death.
AB  - Acid-sensing ion channel 1a (ASIC1a) is the key proton receptor in nervous
      systems, mediating acidosis-induced neuronal injury in many neurological
      disorders, such as ischemic stroke. Up to now, functional ASIC1a has been found
      exclusively on the plasma membrane. Here, we show that ASIC1a proteins are also
      present in mitochondria of mouse cortical neurons where they are physically
      associated with adenine nucleotide translocase. Moreover, purified mitochondria
      from ASIC1a(-/-) mice exhibit significantly enhanced Ca(2+) retention capacity
      and accelerated Ca(2+) uptake rate. When challenged with hydrogen peroxide
      (H2O2), ASIC1a(-/-) neurons are resistant to cytochrome c release and inner
      mitochondrial membrane depolarization, suggesting an impairment of mitochondrial
      permeability transition (MPT) due to ASIC1a deletion. Consistently, H2O2-induced
      neuronal death, which is MPT dependent, is reduced in ASIC1a(-/-) neurons.
      Additionally, significant increases in mitochondrial size and oxidative stress
      levels are detected in ASIC1a(-/-) mouse brain, which also displays marked
      changes (>2-fold) in the expression of mitochondrial proteins closely related to
      reactive oxygen species signal pathways, as revealed by two-dimensional
      difference gel electrophoresis followed by mass spectrometry analysis. Our data
      suggest that mitochondrial ASIC1a may serve as an important regulator of MPT
      pores, which contributes to oxidative neuronal cell death. 

PMID- 23852372
TI  - The Hippo pathway kinase Lats2 prevents DNA damage-induced apoptosis through
      inhibition of the tyrosine kinase c-Abl.
AB  - The Hippo pathway is an evolutionarily conserved pathway that controls cell
      proliferation, organ size, tissue regeneration and stem cell self-renewal. Here
      we show that it also regulates the DNA damage response. At high cell density,
      when the Hippo pathway is active, DNA damage-induced apoptosis and the activation
      of the tyrosine kinase c-Abl were suppressed. At low cell density, overexpression
      of the Hippo pathway kinase large tumor suppressor 2 (Lats2) inhibited c-Abl
      activity. This led to reduced phosphorylation of downstream c-Abl substrates, the
      transcription coactivator Yes-associated protein (Yap) and the tumor suppressor
      p73. Inhibition of c-Abl by Lats2 was mediated through Lats2 interaction with and
      phosphorylation of c-Abl. Lats2 knockdown, or expression of c-Abl mutants that
      escape inhibition by Lats2, enabled DNA damage-induced apoptosis of densely
      plated cells, while Lats2 overexpression inhibited apoptosis in sparse cells.
      These findings explain a long-standing enigma of why densely plated cells are
      radioresistant. Furthermore, they demonstrate that the Hippo pathway regulates
      cell fate decisions in response to DNA damage. 

PMID- 23852373
TI  - Molecular mechanisms of ATP secretion during immunogenic cell death.
AB  - The immunogenic demise of cancer cells can be induced by various
      chemotherapeutics, such as anthracyclines and oxaliplatin, and provokes an immune
      response against tumor-associated antigens. Thus, immunogenic cell death (ICD)
      inducing antineoplastic agents stimulate a tumor-specific immune response that
      determines the long-term success of therapy. The release of ATP from dying cells
      constitutes one of the three major hallmarks of ICD and occurs independently of
      the two others, namely, the pre-apoptotic exposure of calreticulin on the cell
      surface and the postmortem release of high-mobility group box 1 (HMBG1) into the
      extracellular space. Pre-mortem autophagy is known to be required for the ICD
      associated secretion of ATP, implying that autophagy-deficient cancer cells fail
      to elicit therapy-relevant immune responses in vivo. However, the precise
      molecular mechanisms whereby ATP is actively secreted in the course of ICD remain
      elusive. Using a combination of pharmacological screens, silencing experiments
      and techniques to monitor the subcellular localization of ATP, we show here that,
      in response to ICD inducers, ATP redistributes from lysosomes to autolysosomes
      and is secreted by a mechanism that requires the lysosomal protein LAMP1, which
      translocates to the plasma membrane in a strictly caspase-dependent manner. The
      secretion of ATP additionally involves the caspase-dependent activation of Rho
      associated, coiled-coil containing protein kinase 1 (ROCK1)-mediated, myosin II
      dependent cellular blebbing, as well as the opening of pannexin 1 (PANX1)
      channels, which is also triggered by caspases. Of note, although autophagy and
      LAMP1 fail to influence PANX1 channel opening, PANX1 is required for the ICD
      associated translocation of LAMP1 to the plasma membrane. Altogether, these
      findings suggest that caspase- and PANX1-dependent lysosomal exocytosis has an
      essential role in ATP release as triggered by immunogenic chemotherapy. 

PMID- 23852374
TI  - The DNA damage checkpoint precedes activation of ARF in response to escalating
      oncogenic stress during tumorigenesis.
AB  - Oncogenic stimuli trigger the DNA damage response (DDR) and induction of the
      alternative reading frame (ARF) tumor suppressor, both of which can activate the
      p53 pathway and provide intrinsic barriers to tumor progression. However, the
      respective timeframes and signal thresholds for ARF induction and DDR activation
      during tumorigenesis remain elusive. Here, these issues were addressed by
      analyses of mouse models of urinary bladder, colon, pancreatic and skin
      premalignant and malignant lesions. Consistently, ARF expression occurred at a
      later stage of tumor progression than activation of the DDR or p16(INK4A), a
      tumor-suppressor gene overlapping with ARF. Analogous results were obtained in
      several human clinical settings, including early and progressive lesions of the
      urinary bladder, head and neck, skin and pancreas. Mechanistic analyses of
      epithelial and fibroblast cell models exposed to various oncogenes showed that
      the delayed upregulation of ARF reflected a requirement for a higher,
      transcriptionally based threshold of oncogenic stress, elicited by at least two
      oncogenic 'hits', compared with lower activation threshold for DDR. We propose
      that relative to DDR activation, ARF provides a complementary and delayed barrier
      to tumor development, responding to more robust stimuli of escalating oncogenic
      overload. 

PMID- 23852375
TI  - Epigenetic silencing of Bim transcription by Spi-1/PU.1 promotes apoptosis
      resistance in leukaemia.
AB  - Deregulation of transcriptional networks contributes to haematopoietic
      malignancies. The transcription factor Spi-1/PU.1 is a master regulator of
      haematopoiesis and its alteration leads to leukaemia. Spi-1 overexpression
      inhibits differentiation and promotes resistance to apoptosis in
      erythroleukaemia. Here, we show that Spi-1 inhibits mitochondrial apoptosis in
      vitro and in vivo through the transcriptional repression of Bim, a proapoptotic
      factor. BIM interacts with MCL-1 that behaves as a major player in the survival
      of the preleukaemic cells. The repression of BIM expression reduces the amount of
      BIM-MCL-1 complexes, thus increasing the fraction of potentially active
      antiapoptotic MCL-1. We then demonstrate that Spi-1 represses Bim transcription
      by binding to the Bim promoter and by promoting the trimethylation of histone 3
      on lysine 27 (H3K27me3, a repressive histone mark) on the Bim promoter. The PRC2
      repressive complex of Polycomb is directly responsible for the deposit of
      H3K27me3 mark at the Bim promoter. SUZ12 and the histone methyltransferase EZH2,
      two PRC2 subunits bind to the Bim promoter at the same location than H3K27me3,
      distinct of the Spi-1 DNA binding site. As Spi-1 interacts with SUZ12 and EZH2,
      these results indicate that Spi-1 modulates the activity of PRC2 without directly
      recruiting the complex to the site of its activity on the chromatin. Our results
      identify a new mechanism whereby Spi-1 represses transcription and provide
      mechanistic insights on the antiapoptotic function of a transcription factor
      mediated by the epigenetic control of gene expression. 

PMID- 23852376
TI  - Seeing the chemistry in biology with neutron crystallography.
AB  - New developments in macromolecular neutron crystallography have led to an
      increasing number of structures published over the last decade. Hydrogen atoms,
      normally invisible in most X-ray crystal structures, become visible with
      neutrons. Using X-rays allows one to see structure, while neutrons allow one to
      reveal the chemistry inherent in these macromolecular structures. A number of
      surprising and sometimes controversial results have emerged; because it is
      difficult to see or predict hydrogen atoms in X-ray structures, when they are
      seen by neutrons they can be in unexpected locations with important chemical and
      biological consequences. Here we describe examples of chemistry seen with
      neutrons for the first time in biological macromolecules over the past few years.

PMID- 23852377
TI  - Effect of all-trans retinoic acid on the differentiation of U87 glioma
      stem/progenitor cells.
AB  - GSPCs (glioma stem/progenitor cells) were isolated from U87 glioma cell lines by
      serum-free neural stem cell medium. Four concentrations (1, 2, 4, and 8 MUmol/L)
      of ATRA (all-trans retinoic acid) were used to induce the differentiation of
      GSPCs in the medium with or without growth factors. The effect of ATRA on the
      differentiation of GSPCs was analyzed by flow cytometry, real-time-PCR, and
      immunofluorescence. The differentiation of GSPCs could be induced by 1 or 2
      MUmol/L ATRA when GSPCs were cultured in growth factor-free medium. The detection
      of real-time-PCR showed that the level of GFAP (glial fibrillary acidic protein)
      mRNA of differentiated GSPCs in the growth factor-free medium containing 1
      MUmol/L ATRA group was significantly higher than that in the control group, and
      there was no significant difference in the level of TUBB-3 mRNA between the two
      groups. The GSPCs suffered apoptosis in the growth factor-free medium containing
      4 or 8 MUmol/L ATRA. The differentiation of GSPCs could not be induced by ATRA
      when GSPCs were cultured in the medium containing growth factors. The percentage
      of cells in G0/G1 phase was 84.26 +/- 2.24 %, and the percentage of apoptosis was
      18.95 +/- 2.53 % in experimental groups which was similar to those in the control
      group. In conclusion, ATRA has certain capacity to induce differentiation of
      GSPCs, while its effective concentration should be controlled strictly. The
      differentiation of GSPCs induced by ATRA cannot antagonize the formidable
      differential inhibition of epidermal growth factor and basic fibroblast growth
      factor.

PMID- 23852378
TI  - Apomixis in plant reproduction: a novel perspective on an old dilemma.
AB  - Seed is one of the key factors of crop productivity. Therefore, a comprehension
      of the mechanisms underlying seed formation in cultivated plants is crucial for
      the quantitative and qualitative progress of agricultural production. In
      angiosperms, two pathways of reproduction through seed exist: sexual or
      amphimictic, and asexual or apomictic; the former is largely exploited by seed
      companies for breeding new varieties, whereas the latter is receiving
      continuously increasing attention from both scientific and industrial sectors in
      basic research projects. If apomixis is engineered into sexual crops in a
      controlled manner, its impact on agriculture will be broad and profound. In fact,
      apomixis will allow clonal seed production and thus enable efficient and
      consistent yields of high-quality seeds, fruits, and vegetables at lower costs.
      The development of apomixis technology is expected to have a revolutionary impact
      on agricultural and food production by reducing cost and breeding time, and
      avoiding the complications that are typical of sexual reproduction (e.g.,
      incompatibility barriers) and vegetative propagation (e.g., viral transfer).
      However, the development of apomixis technology in agriculture requires a deeper
      knowledge of the mechanisms that regulate reproductive development in plants.
      This knowledge is a necessary prerequisite to understanding the genetic control
      of the apomictic process and its deviations from the sexual process. Our
      molecular understanding of apomixis will be greatly advanced when genes that are
      specifically or differentially expressed during embryo and embryo sac formation
      are discovered. In our review, we report the main findings on this subject by
      examining two approaches: i) analysis of the apomictic process in natural
      apomictic species to search for genes controlling apomixis and ii) analysis of
      gene mutations resembling apomixis or its components in species that normally
      reproduce sexually. In fact, our opinion is that a novel perspective on this old
      dilemma pertaining to the molecular control of apomixis can emerge from a cross
      check among candidate genes in natural apomicts and a high-throughput analysis of
      sexual mutants. 

PMID- 23852379
TI  - Control of the meiotic cell division program in plants.
AB  - While the question of why organisms reproduce sexually is still a matter of
      controversy, it is clear that the foundation of sexual reproduction is the
      formation of gametes with half the genomic DNA content of a somatic cell. This
      reduction in genomic content is accomplished through meiosis that, in contrast to
      mitosis, comprises two subsequent chromosome segregation steps without an
      intervening S phase. In addition, meiosis generates new allele combinations
      through the compilation of new sets of homologous chromosomes and the reciprocal
      exchange of chromatid segments between homologues. Progression through meiosis
      relies on many of the same, or at least homologous, cell cycle regulators that
      act in mitosis, e.g., cyclin-dependent kinases and the anaphase-promoting
      complex/cyclosome. However, these mitotic control factors are often
      differentially regulated in meiosis. In addition, several meiosis-specific cell
      cycle genes have been identified. We here review the increasing knowledge on
      meiotic cell cycle control in plants. Interestingly, plants appear to have
      relaxed cell cycle checkpoints in meiosis in comparison with animals and yeast
      and many cell cycle mutants are viable. This makes plants powerful models to
      study meiotic progression and allows unique modifications to their meiotic
      program to develop new plant-breeding strategies. 

PMID- 23852380
TI  - Microspore embryogenesis: establishment of embryo identity and pattern in
      culture.
AB  - The developmental plasticity of plants is beautifully illustrated by the
      competence of the immature male gametophyte to change its developmental fate from
      pollen to embryo development when exposed to stress treatments in culture. This
      process, referred to as microspore embryogenesis, is widely exploited in plant
      breeding, but also provides a unique system to understand totipotency and early
      cell fate decisions. We summarize the major concepts that have arisen from
      decades of cell and molecular studies on microspore embryogenesis and put these
      in the context of recent experiments, as well as results obtained from the study
      of pollen and zygotic embryo development. 

PMID- 23852381
TI  - Oral human papillomavirus infection and head and neck cancers in HIV-infected
      individuals.
AB  - PURPOSE OF REVIEW: HIV-infected individuals are living longer due to effective
      antiretroviral therapy and may therefore have a greater opportunity to develop
      human papillomavirus (HPV)-associated malignancies. This review describes the
      risk factors and burden of oral HPV infection and HPV-associated head and neck
      cancer (HNC) among HIV-infected individuals. RECENT FINDINGS: Oral HPV infection
      is commonly detected in HIV-infected individuals and is elevated among those with
      a higher number of lifetime oral sexual partners, current tobacco use and
      immunosuppression. There are limited data on the natural history of oral HPV, but
      initial studies suggest that the majority of infections clear within 2 years.
      Although HIV-infected individuals are at a much higher risk of most HPV
      associated cancers than the general population, studies suggest HIV-infected
      individuals have a more modest 1.5-4-fold greater risk for HPV-associated HNC.
      SUMMARY: HIV-infected individuals are living longer, have a high prevalence of
      oral HPV infection and have many of the currently determined risk factors for HPV
      associated HNC.

PMID- 23852382
TI  - MicroRNAs in lymphoma, from diagnosis to targeted therapy.
AB  - PURPOSE OF REVIEW: The crucial role of microRNAs (miRNAs) in major biological
      processes and cancer development has been extensively described. Some stage
      specific miRNAs are involved in B-cell differentiation, from the naive B-cell
      stage through germinal center maturation. Assuming that lymphoma cells are
      derived from B cells at different stages of maturation, miRNAs can be considered
      as both specific markers and putative target genes. Here, we review the most
      salient recent publications in this field, highlighting the clinical and
      therapeutic value of miRNAs in lymphomas. RECENT FINDINGS: miRNA array-based
      experiments have indicated that almost all mature lymphoid malignancies can be
      characterized by a distinct miRNA profile. Recent works have highlighted the
      crucial roles of miR-155 and miR-17-92 in the pathogeneses of diffuse large B
      cell lymphoma and mantle cell lymphoma, respectively, indicating that they
      represent promising target genes. Novel mechanisms of miRNA deregulation have
      also been reported, including recurrent somatic mutations, MYC-driven miRNA
      repression, and cross-talk with other cells in the microenvironment. SUMMARY: In
      experimental models, some lymphomas are considered to be addicted to the
      sustained expression of targetable oncomiRs, such as miR-155 and miR-21. However,
      despite these results, which provide considerable information regarding lymphoma
      pathogenesis, the integration of miRNA analysis for lymphoma diagnosis or
      treatment in daily practice remains challenging.

PMID- 23852383
TI  - Correlation between mutation rate and genome size in riboviruses: mutation rate
      of bacteriophage Qbeta.
AB  - Genome sizes and mutation rates covary across all domains of life. In unicellular
      organisms and DNA viruses, they show an inverse relationship known as Drake's
      rule. However, it is still unclear whether a similar relationship exists between
      genome sizes and mutation rates in RNA genomes. Coronaviruses, the RNA viruses
      with the largest genomes (~30 kb), encode a proofreading 3' exonuclease that
      allows them to increase replication fidelity. However, it is unknown whether,
      conversely, the RNA viruses with the smallest genomes tend to show particularly
      high mutation rates. To test this, we measured the mutation rate of bacteriophage
      Qbeta, a 4.2-kb levivirus. Amber reversion-based Luria-Delbruck fluctuation tests
      combined with mutant sequencing gave an estimate of 1.4 * 10(-4) substitutions
      per nucleotide per round of copying, the highest mutation rate reported for any
      virus using this method. This estimate was confirmed using a direct plaque
      sequencing approach and after reanalysis of previously published estimates for
      this phage. Comparison with other riboviruses (all RNA viruses except
      retroviruses) provided statistical support for a negative correlation between
      mutation rates and genome sizes. We suggest that the mutation rates of RNA
      viruses might be optimized for maximal adaptability and that the value of this
      optimum may in turn depend inversely on genome size. 

PMID- 23852384
TI  - Models of frequency-dependent selection with mutation from parental alleles.
AB  - Frequency-dependent selection (FDS) remains a common heuristic explanation for
      the maintenance of genetic variation in natural populations. The pairwise
      interaction model (PIM) is a well-studied general model of frequency-dependent
      selection, which assumes that a genotype's fitness is a function of within
      population intergenotypic interactions. Previous theoretical work indicated that
      this type of model is able to sustain large numbers of alleles at a single locus
      when it incorporates recurrent mutation. These studies, however, have ignored the
      impact of the distribution of fitness effects of new mutations on the dynamics
      and end results of polymorphism construction. We suggest that a natural way to
      model mutation would be to assume mutant fitness is related to the fitness of the
      parental allele, i.e., the existing allele from which the mutant arose. Here we
      examine the numbers and distributions of fitnesses and alleles produced by
      construction under the PIM with mutation from parental alleles and the impacts on
      such measures due to different methods of generating mutant fitnesses. We find
      that, in comparison with previous results, generating mutants from existing
      alleles lowers the average number of alleles likely to be observed in a system
      subject to FDS, but produces polymorphisms that are highly stable and have
      realistic allele-frequency distributions. 

PMID- 23852386
TI  - Viability, longevity, and egg production of Drosophila melanogaster are regulated
      by the miR-282 microRNA.
AB  - The first microRNAs were discovered some 20 years ago, but only a small fraction
      of the microRNA-encoding genes have been described in detail yet. Here we report
      the molecular analysis of a computationally predicted Drosophila melanogaster
      microRNA gene, mir-282. We show that the mir-282 gene is the source of a 4.9-kb
      long primary transcript with a 5' cap and a 3'-poly(A) sequence and a mature
      microRNA of ~25 bp. Our data strongly suggest the existence of an independent mir
      282 gene conserved in holometabolic insects. We give evidence that the mir-282
      locus encodes a functional transcript that influences viability, longevity, and
      egg production in Drosophila. We identify the nervous system-specific adenylate
      cyclase (rutabaga) as a target of miR-282 and assume that one of the main
      functions of mir-282 is the regulation of adenylate cyclase activity in the
      nervous system during metamorphosis. 

PMID- 23852385
TI  - A new system for comparative functional genomics of Saccharomyces yeasts.
AB  - Whole-genome sequencing, particularly in fungi, has progressed at a tremendous
      rate. More difficult, however, is experimental testing of the inferences about
      gene function that can be drawn from comparative sequence analysis alone. We
      present a genome-wide functional characterization of a sequenced but
      experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum
      (henceforth referred to as S. bayanus), allowing us to map changes over the 20
      million years that separate this organism from S. cerevisiae. We first created a
      suite of genetic tools to facilitate work in S. bayanus. Next, we measured the
      gene-expression response of S. bayanus to a diverse set of perturbations
      optimized using a computational approach to cover a diverse array of functionally
      relevant biological responses. The resulting data set reveals that gene
      expression patterns are largely conserved, but significant changes may exist in
      regulatory networks such as carbohydrate utilization and meiosis. In addition to
      regulatory changes, our approach identified gene functions that have diverged.
      The functions of genes in core pathways are highly conserved, but we observed
      many changes in which genes are involved in osmotic stress, peroxisome
      biogenesis, and autophagy. A surprising number of genes specific to S. bayanus
      respond to oxidative stress, suggesting the organism may have evolved under
      different selection pressures than S. cerevisiae. This work expands the scope of
      genome-scale evolutionary studies from sequence-based analysis to rapid
      experimental characterization and could be adopted for functional mapping in any
      lineage of interest. Furthermore, our detailed characterization of S. bayanus
      provides a valuable resource for comparative functional genomics studies in
      yeast. 

PMID- 23852388
TI  - Mefloquine use, psychosis, and violence: a retinoid toxicity hypothesis.
AB  - Mefloquine use has been linked to severe gastrointestinal and neuropsychiatric
      adverse effects, including cognitive disturbances, anxiety, depression,
      psychosis, and violence. The adverse effects of the drug are thought to result
      from the secondary consequences of hepatocellular injury; in fact, mefloquine is
      known to cause a transient, anicteric chemical hepatitis. However, the mechanism
      of mefloquine-associated liver damage and the associated neuropsychiatric and
      behavioral effects of the drug are not well understood. Mefloquine and other 8
      amino-quinolines are the only antimalarial drugs that target the liver-stage
      malaria parasites, which selectively absorb vitamin A from the host. Vitamin A is
      also stored mainly in the liver, in potentially poisonous concentrations. These
      observations suggest that both the therapeutic effectiveness of mefloquine and
      its adverse effects are related to the ability of the 8-aminoquinolines to alter
      the metabolism of retinoids (vitamin A and its congeners). Several lines of
      evidence support the hypothesis that mefloquine neurotoxicity and other adverse
      effects reflect an endogenous form of hypervitaminosis A due to a process
      involving: mefloquine-induced dehydrogenase inhibition; the accumulation of
      retinoids in the liver; retinoid-induced hepatocellular damage; the spillage of
      stored retinoids into the circulation; and the transport of these compounds to
      the gut and brain in toxic concentrations. The retinoid hypothesis could be
      tested clinically by comparing cases of mefloquine toxicity and untreated
      controls in terms of retinoid profiles (retinol, retinyl esters, percent retinyl
      esters, and retinoic acid). Subject to such tests, retinoid profiling could
      provide an indicator for assessing mefloquine-associated adverse effects. 

PMID- 23852387
TI  - Association of maternal mRNA and phosphorylated EIF4EBP1 variants with the
      spindle in mouse oocytes: localized translational control supporting female
      meiosis in mammals.
AB  - In contrast to other species, localized maternal mRNAs are not believed to be
      prominent features of mammalian oocytes. We find by cDNA microarray analysis
      enrichment for maternal mRNAs encoding spindle and other proteins on the mouse
      oocyte metaphase II (MII) spindle. We also find that the key translational
      regulator, EIF4EBP1, undergoes a dynamic and complex spatially regulated pattern
      of phosphorylation at sites that regulate its association with EIF4E and its
      ability to repress translation. These phosphorylation variants appear at
      different positions along the spindle at different stages of meiosis. These
      results indicate that dynamic spatially restricted patterns of EIF4EBP1
      phosphorylation may promote localized mRNA translation to support spindle
      formation, maintenance, function, and other nearby processes. Regulated EIF4EBP1
      phosphorylation at the spindle may help coordinate spindle formation with
      progression through the cell cycle. The discovery that EIF4EBP1 may be part of an
      overall mechanism that integrates and couples cell cycle progression to mRNA
      translation and subsequent spindle formation and function may be relevant to
      understanding mechanisms leading to diminished oocyte quality, and potential
      means of avoiding such defects. The localization of maternal mRNAs at the spindle
      is evolutionarily conserved between mammals and other vertebrates and is also
      seen in mitotic cells, indicating that EIF4EBP1 control of localized mRNA
      translation is likely key to correct segregation of genetic material across cell
      types. 

PMID- 23852389
TI  - Does surface wettability influence the friction and wear of large-diameter CoCrMo
      alloy hip resurfacings?
AB  - The role of surface tension in the lubrication of metal-on-metal (CoCrMo alloy)
      hip resurfacings has been investigated to try to explain why all metal joints
      fail to be lubricated with simple water-based lubricants (sodium carboxymethyl
      cellulose), which have similar rheology to synovial fluid, but are lubricated
      with the same fluid with the addition of a proportion of bovine serum. As part of
      this study, surfactants, in the form of detergents, when added to carboxymethyl
      cellulose, have been shown to produce a predominantly fluid-film lubrication
      mechanism with friction even lower than the biological lubricant containing
      serum. Friction factors were reduced by 80% when a detergent was added to the
      lubricant. It is considered that the failure of the water-based fluids to
      generate fluid-film lubrication is due to the fact that 'boundary slip' takes
      place where the fluid does not fully attach to the bounding solid surfaces as
      assumed in Reynolds' equation, thereby drawing in less lubricant than predicted
      from hydrodynamic theory. The addition of surfactants either in the form of
      natural materials such as serum or in the form of detergent reduces surface
      tension and helps the water-based lubricant to attach more fully to the bounding
      surfaces resulting in more fluid entrainment and thicker fluid-film formation.
      This was confirmed by up to 70% lower wear being found when these joints were
      lubricated in a detergent solution rather than 25% bovine serum. 

PMID- 23852391
TI  - Bioluminescent orthotopic model of pancreatic cancer progression.
AB  - Pancreatic cancer has an extremely poor five-year survival rate of 4-6%. New
      therapeutic options are critically needed and depend on improved understanding of
      pancreatic cancer biology. To better understand the interaction of cancer cells
      with the pancreatic microenvironment, we demonstrate an orthotopic model of
      pancreatic cancer that permits non-invasive monitoring of cancer progression.
      Luciferase-tagged pancreatic cancer cells are resuspended in Matrigel and
      delivered into the pancreatic tail during laparotomy. Matrigel solidifies at body
      temperature to prevent leakage of cancer cells during injection. Primary tumor
      growth and metastasis to distant organs are monitored following injection of the
      luciferase substrate luciferin, using in vivo imaging of bioluminescence emission
      from the cancer cells. In vivo imaging also may be used to track primary tumor
      recurrence after resection. This orthotopic model is suited to both syngeneic and
      xenograft models and may be used in pre-clinical trials to investigate the impact
      of novel anti-cancer therapeutics on the growth of the primary pancreatic tumor
      and metastasis. 

PMID- 23852390
TI  - Combining trail with PI3 kinase or HSP90 inhibitors enhances apoptosis in
      colorectal cancer cells via suppression of survival signaling.
AB  - TRAIL has been shown to induce apoptosis in cancer cells, but in some cases they
      fail to respond to this ligand. We explored the ability of representative
      phosphatidylinositol-3-kinase (PI3 Kinase)/mTOR and HSP90 inhibitors to overcome
      TRAIL resistance by increasing apoptosis in colorectal cancer models. We
      determined the sensitivity of 27 human colorectal cancer and 2 non-transformed
      colon epithelial cell lines to TRAIL treatment. A subset of the cancer cell lines
      with a range of responses to TRAIL was selected from the panel for treatment with
      TRAIL combined with the PI3 Kinase/mTOR inhibitor PI-103 or the HSP90 inhibitor
      17-AAG (tanespimycin). Two TRAIL-resistant cell lines were selected for in vivo
      combination studies with TRAIL and 17-AAG. We found that 13 colorectal cancer
      cell lines and the 2 non-transformed colon epithelial cell lines were resistant
      to TRAIL. We demonstrated that co-treatment of TRAIL and PI-103 or 17-AAG was
      synergistic or additive and significantly enhanced apoptosis in colorectal cancer
      cells. This was associated with decreased expression or activity of survival
      protein biomarkers such as ERBB2, AKT, IKKalpha and XIAP. In contrast, the effect
      of the combination treatments in non-transformed colon cells was minimal. We show
      here for the first time that co-treatment in vivo with TRAIL and 17-AAG in two
      TRAIL-resistant human colorectal cancer xenograft models resulted in
      significantly greater tumor growth inhibition compared to single treatments. We
      propose that combining TRAIL with PI3 Kinase/mTOR or HSP90 inhibitors has
      therapeutic potential in the treatment of TRAIL-resistant colorectal cancers. 

PMID- 23852392
TI  - Isolation of human atrial myocytes for simultaneous measurements of Ca2+
      transients and membrane currents.
AB  - The study of electrophysiological properties of cardiac ion channels with the
      patch-clamp technique and the exploration of cardiac cellular Ca(2+) handling
      abnormalities requires isolated cardiomyocytes. In addition, the possibility to
      investigate myocytes from patients using these techniques is an invaluable
      requirement to elucidate the molecular basis of cardiac diseases such as atrial
      fibrillation (AF).(1) Here we describe a method for isolation of human atrial
      myocytes which are suitable for both patch-clamp studies and simultaneous
      measurements of intracellular Ca(2+) concentrations. First, right atrial
      appendages obtained from patients undergoing open heart surgery are chopped into
      small tissue chunks ("chunk method") and washed in Ca(2+)-free solution. Then the
      tissue chunks are digested in collagenase and protease containing solutions with
      20 MUM Ca(2+). Thereafter, the isolated myocytes are harvested by filtration and
      centrifugation of the tissue suspension. Finally, the Ca(2+) concentration in the
      cell storage solution is adjusted stepwise to 0.2 mM. We briefly discuss the
      meaning of Ca(2+) and Ca(2+) buffering during the isolation process and also
      provide representative recordings of action potentials and membrane currents,
      both together with simultaneous Ca(2+) transient measurements, performed in these
      isolated myocytes. 

PMID- 23852393
TI  - Renin-angiotensin-aldosterone system inhibitors in heart failure.
AB  - Heart failure (HF) is a very common condition that, despite advances in
      treatment, carries significant morbidity and mortality. Although there is good
      evidence for the treatment of HF with reduced ejection fraction (HFrEF), the
      treatment for HF with preserved ejection fraction (HFpEF) is not well defined.
      The renin-angiotensin-aldosterone system (RAAS) has been shown to be an effective
      target in the treatment of HFrEF using angiotensin-converting enzyme inhibitors,
      angiotensin receptor blockers, and aldosterone blockade, although the evidence in
      HFpEF is less clear. This review aims to look first at the evidence for these
      drugs, and second at the newer drugs that act on the RAAS, namely, direct renin
      inhibitors, neutral endopeptidase inhibitors, vasopeptidase inhibitors, and
      angiotensin receptor blockers.

PMID- 23852394
TI  - The high-risk patient with heart failure with reduced ejection fraction:
      treatment options and challenges.
AB  - An estimated 5.1 million Americans aged 20 years and older have heart failure.(1)
      With therapies ranging from medication and physical therapy to implantable
      defibrillators and circulatory support, and possibly transplantation, accurate
      risk stratification of patient with heart failure and delivery of therapies
      appropriate to the level of their disease severity is becoming increasingly
      important. Determination of risk and associated treatment strategies is the
      subject of this brief review.

PMID- 23852395
TI  - MicroRNAs in heart failure: new targets in disease management.
AB  - Heart failure is the leading cause of mortality in Western society and represents
      the fastest growing subclass of cardiovascular diseases. An increasing body of
      evidence indicates an important role for microRNAs (miRNAs) in the pathogenesis
      and progression of heart failure. miRNAs are small noncoding RNAs that regulate
      expression of target genes by sequence-specific binding to the 3' untranslated
      region of messenger RNA, which results in degradation or translational
      repression. To date, many miRNAs (and their targets) that play a role in diverse
      aspects of cardiac remodeling and heart failure development have been identified.
      Here, we give an overview of these miRNAs and their role in cardiac pathogenesis.
      In addition, we provide brief insight into the potential of miRNAs as novel
      therapeutic targets for heart failure.

PMID- 23852396
TI  - Diuretic use in heart failure and outcomes.
AB  - Diuretics are frequently administered to relieve congestive symptoms in patients
      with heart failure (HF). Despite their widespread use, prospective data on the
      potential of diuretics to modulate HF-related morbidity and mortality are scarce.
      Diuretic efficacy may be limited by adverse neurohormonal activation and by
      "congestion-like" symptoms that may occur in the absence of fluid overload.
      Herein, we review the current knowledge on diuretic use and outcomes in HF.

PMID- 23852397
TI  - A randomized phase II study comparing S-1 plus weekly split-dose cisplatin with S
      1 plus standard-dose cisplatin as first-line chemotherapy for advanced gastric
      cancer.
AB  - BACKGROUND: S-1 plus weekly split-dose cisplatin demonstrated promising results
      in previous phase I and II studies for advanced gastric cancer (AGC) patients.
      METHODS: In this randomized phase II study, the efficacy and safety of S-1 plus
      weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80-120 mg according to
      body surface area on days 1-14, and cisplatin 20 mg/m(2) i.v. on days 1 and 8
      every 3 weeks) were compared with those of S-1 plus standard-dose cisplatin (SP)
      as first-line chemotherapy for AGC patients. The primary endpoint was 1-year
      survival rate. RESULTS: Patients were randomized into two groups: 18 in the SWP
      arm and 19 in the SP arm. This trial was terminated early because of low patient
      enrollment. The 1-year survival rate was 61 % [95 % confidence interval (CI), 36
      86 %] and 53 % (95 % CI, 30-75 %) in the SWP and SP arms, respectively. However,
      the median survival time was 12.3 months (9.9-14.6 months) and 15.7 months (4.0
      27.4 months), respectively (P = 0.064). Progression-free survival was
      significantly shorter in the SWP arm than in the SP arm (P = 0.047). Toxicity
      tended to be milder in the SWP arm than in the SP arm. For approximately 40 % of
      patients in the SWP arm, cisplatin was omitted on day 8 and treatment delayed
      because of prolonged myelosuppression. CONCLUSIONS: No clear benefits of adding
      cisplatin to S-1 in the SWP arm were demonstrated in this study. At this point,
      split-dose cisplatin combined with S-1 cannot be recommended for use in clinical
      practice.

PMID- 23852398
TI  - Reversible anionic redox chemistry in high-capacity layered-oxide electrodes.
AB  - Li-ion batteries have contributed to the commercial success of portable
      electronics and may soon dominate the electric transportation market provided
      that major scientific advances including new materials and concepts are
      developed. Classical positive electrodes for Li-ion technology operate mainly
      through an insertion-deinsertion redox process involving cationic species.
      However, this mechanism is insufficient to account for the high capacities
      exhibited by the new generation of Li-rich (Li(1+x)Ni(y)Co(z)Mn(1-x-y-z)O2)
      layered oxides that present unusual Li reactivity. In an attempt to overcome both
      the inherent composition and the structural complexity of this class of oxides,
      we have designed structurally related Li2Ru(1-y)Sn(y)O3 materials that have a
      single redox cation and exhibit sustainable reversible capacities as high as 230
      mA h g(-1). Moreover, they present good cycling behaviour with no signs of
      voltage decay and a small irreversible capacity. We also unambiguously show, on
      the basis of an arsenal of characterization techniques, that the reactivity of
      these high-capacity materials towards Li entails cumulative cationic (M(n+)
      >M((n+1)+)) and anionic (O(2-)->O2(2-)) reversible redox processes, owing to the
      d-sp hybridization associated with a reductive coupling mechanism. Because Li2MO3
      is a large family of compounds, this study opens the door to the exploration of a
      vast number of high-capacity materials.

PMID- 23852399
TI  - Epitaxial growth of single-domain graphene on hexagonal boron nitride.
AB  - Hexagonal boron nitride (h-BN) has recently emerged as an excellent substrate for
      graphene nanodevices, owing to its atomically flat surface and its potential to
      engineer graphene's electronic structure. Thus far, graphene/h-BN
      heterostructures have been obtained only through a transfer process, which
      introduces structural uncertainties due to the random stacking between graphene
      and h-BN substrate. Here we report the epitaxial growth of single-domain graphene
      on h-BN by a plasma-assisted deposition method. Large-area graphene single
      crystals were successfully grown for the first time on h-BN with a fixed stacking
      orientation. A two-dimensional (2D) superlattice of trigonal moire pattern was
      observed on graphene by atomic force microscopy. Extra sets of Dirac points are
      produced as a result of the trigonal superlattice potential and the quantum Hall
      effect is observed with the 2D-superlattice-related feature developed in the fan
      diagram of longitudinal and Hall resistance, and the Dirac fermion physics near
      the original Dirac point is unperturbed. The macroscopic epitaxial graphene is in
      principle limited only by the size of the h-BN substrate and our synthesis method
      is potentially applicable on other flat surfaces. Our growth approach could thus
      open new ways of graphene band engineering through epitaxy on different
      substrates. 

PMID- 23852401
TI  - Generation, transport and detection of valley-polarized electrons in diamond.
AB  - Standard electronic devices encode bits of information by controlling the amount
      of electric charge in the circuits. Alternatively, it is possible to make devices
      that rely on other properties of electrons than their charge. For example,
      spintronic devices make use of the electron spin angular momentum as a carrier of
      information. A new concept is valleytronics in which information is encoded by
      the valley quantum number of the electron. The analogy between the valley and
      spin degrees of freedom also implies the possibility of valley-based quantum
      computing. In this Article, we demonstrate for the first time generation,
      transport (across macroscopic distances) and detection of valley-polarized
      electrons in bulk diamond with a relaxation time of 300 ns at 77 K. We anticipate
      that these results will form the basis for the development of integrated
      valleytronic devices. 

PMID- 23852400
TI  - Thermoelectric imaging of structural disorder in epitaxial graphene.
AB  - Heat is a familiar form of energy transported from a hot side to a colder side of
      an object, but not a notion associated with microscopic measurements of
      electronic properties. A temperature difference within a material causes charge
      carriers, electrons or holes to diffuse along the temperature gradient inducing a
      thermoelectric voltage. Here we show that local thermoelectric measurements can
      yield high-sensitivity imaging of structural disorder on the atomic and nanometre
      scales. The thermopower measurement acts to amplify the variations in the local
      density of states at the Fermi level, giving high differential contrast in
      thermoelectric signals. Using this imaging technique, we uncovered point defects
      in the first layer of epitaxial graphene, which generate soliton-like domain-wall
      line patterns separating regions of the different interlayer stacking of the
      second graphene layer. 

PMID- 23852402
TI  - 2-[18F]fludarabine, a novel positron emission tomography (PET) tracer for imaging
      lymphoma: a micro-PET study in murine models.
AB  - PURPOSE: Fludarabine has proven to be of considerable efficacy in the treatment
      of low-grade lymphomas. We have developed the labeling of this drug with fluorine
      18 and evaluated 2-[(18)F]fludarabine as a novel positron emission tomography
      (PET) probe for in vivo imaging. PROCEDURES: Preclinical studies were conducted
      with 2-[(18)F]fludarabine, in parallel with 2-deoxy-2-[(18)F]fluoro-D-glucose
      ([(18)F]FDG), in Swiss CD-1 and CB17 severely combined immunodeficient (SCID)
      mice, both as tumor-free control groups, and SCID mice bearing RL lymphomas.
      RESULTS: In Swiss mice, micro-PET studies with 2-[(18)F]fludarabine showed a
      distribution restricted to the organs of excretion and the spleen, the latter
      being less evident in SCID animals. In lymphoma-bearing SCID mice, 2
      [(18)F]fludarabine demonstrated a rapid tumor uptake over the first 20 min which
      subsequently plateaued and provided an improved contrast than that of [(18)F]FDG.
      CONCLUSION: This radiotracer merits further evaluation to establish its clinical
      usefulness to image low-grade lymphoma in humans in future clinical
      investigations.

PMID- 23852403
TI  - Incidence of food anaphylaxis in Piemonte region (Italy): data from registry of
      Center for Severe Allergic Reactions.
AB  - There are wide differences in estimated incidence and prevalence of anaphylaxis
      because of the absence, until recently, of a universal consensus on the
      definition of anaphylaxis and the different source of collected data. We aimed to
      estimate the incidence of food anaphylaxis based on the database of Piemonte
      Region (Italy) Reference Center for Severe Allergic Reactions. All cases of
      severe food allergic reactions reported in 2010 were studied. Clinical data
      associated to the reports were evaluated according to National Institute of
      Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network
      diagnostic criteria of anaphylaxis. 75 % of the 778 cases were classified as food
      anaphylaxis (incidence of 13/100,000 person-years, ranging from 9.9 in adults to
      29/100,000 person-years in children). Nuts were the most frequent foods causing
      anaphylaxis. Milk and eggs were responsible for anaphylaxis more often in
      children, while peach, vegetables and crustaceans were in adults. Cardiovascular
      symptoms were more frequent in adults. Gastrointestinal involvement was more
      frequent in children. A high prevalence of respiratory allergic comorbidities was
      observed. Food is an important cause of anaphylaxis, particularly in subjects
      with respiratory allergic comorbidities. Children and adults differ in triggers
      and clinical presentation of anaphylaxis. 

PMID- 23852404
TI  - Blood flow dynamic improvement with aneurysm repair detected by a patient
      specific model of multiple aortic aneurysms.
AB  - Aortic aneurysms may cause the turbulence of blood flow and result in the energy
      loss of the blood flow, while grafting of the dilated aorta may ameliorate these
      hemodynamic disturbances, contributing to the alleviation of the energy
      efficiency of blood flow delivery. However, evaluating of the energy efficiency
      of blood flow in an aortic aneurysm has been technically difficult to estimate
      and not comprehensively understood yet. We devised a multiscale computational
      biomechanical model, introducing novel flow indices, to investigate a single male
      patient with multiple aortic aneurysms. Preoperative levels of wall shear stress
      and oscillatory shear index (OSI) were elevated but declined after staged
      grafting procedures: OSI decreased from 0.280 to 0.257 (first operation) and
      0.221 (second operation). Graftings may strategically counter the loss of
      efficient blood delivery to improve hemodynamics of the aorta. The energy
      efficiency of blood flow also improved postoperatively. Novel indices of
      pulsatile pressure index (PPI) and pulsatile energy loss index (PELI) were
      evaluated to characterize and quantify energy loss of pulsatile blood flow. Mean
      PPI decreased from 0.445 to 0.423 (first operation) and 0.359 (second operation),
      respectively; while the preoperative PELI of 0.986 dropped to 0.820 and 0.831.
      Graftings contributed not only to ameliorate wall shear stress or oscillatory
      shear index but also to improve efficient blood flow. This patient-specific
      modeling will help in analyzing the mechanism of aortic aneurysm formation and
      may play an important role in quantifying the energy efficiency or loss in blood
      delivery. 

PMID- 23852406
TI  - Determination of orientations of aromatic groups in self-assembled peptide
      fibrils by polarised Raman spectroscopy.
AB  - In this paper we describe a novel combination of Raman spectroscopy, isotope
      editing and X-ray scattering as a powerful approach to give detailed structural
      information on aromatic side chains in peptide fibrils. The orientation of the
      tyrosine residues in fibrils of the peptide YTIAALLSPYS with respect to the
      fibril axis has been determined from a combination of polarised Raman
      spectroscopy and X-ray diffraction measurements. The Raman intensity of selected
      tyrosine bands collected at different polarisation geometries is related to the
      values and orientation of the Raman tensor for those specific vibrations. Using
      published Raman tensor values we solved the relevant expressions for both of the
      two tyrosine residues present in this peptide. Ring deuteration in one of the two
      tyrosine side chains allowed for the calculation to be performed individually for
      both, by virtue of the isotopic shift that eliminates band overlapping. Sample
      disorder was taken into account by obtaining the distribution of orientations of
      the samples from X-ray diffraction experiments. The results provide previously
      unavailable details about the molecular conformation of this peptide, and
      demonstrate the value of this approach for the study of amyloid fibrils. 

PMID- 23852405
TI  - Impairment of flow-mediated dilation correlates with aortic dilation in patients
      with Marfan syndrome.
AB  - Marfan syndrome is an inherited disorder characterized by genetic abnormality of
      microfibrillar connective tissue proteins. Endothelial dysfunction is thought to
      cause aortic dilation in subjects with a bicuspid aortic valve; however, the role
      of endothelial dysfunction and endothelial damaging factors has not been
      elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement
      of endothelial function, was evaluated in 39 patients with Marfan syndrome.
      Aortic diameter was measured at the aortic annulus, aortic root at the sinus of
      Valsalva, sinotubular junction and ascending aorta by echocardiography, and
      adjusted for body surface area (BSA). The mean value of flow-mediated dilation
      was 6.5 +/- 2.4 %. Flow-mediated dilation had a negative correlation with the
      diameter of the ascending thoracic aorta (AscAd)/BSA (R = -0.39, p = 0.020) and
      multivariate analysis revealed that flow-mediated dilation was an independent
      factor predicting AscAd/BSA, whereas other segments of the aorta had no
      association. Furthermore, Brinkman index had a somewhat greater influence on flow
      mediated dilation (R = -0.42, p = 0.008). Although subjects who smoked tended to
      have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 +/- 1.8 versus 15.2
      +/- 3.0 mm/m(2), p = 0.013), there was no significant change in flow-mediated
      dilation, suggesting that smoking might affect aortic dilation via an independent
      pathway. Common atherogenic risks, such as impairment of flow-mediated dilation
      and smoking status, affected aortic dilation in subjects with Marfan syndrome.

PMID- 23852407
TI  - Symptom clusters of pain, depressed mood, and fatigue in lung cancer: assessing
      the role of cytokine genes.
AB  - PURPOSE: Symptom clusters, the multiple, co-occurring symptoms experienced by
      cancer patients, are debilitating and affects quality of life. We assessed if a
      panel of immune-response genes may underlie the co-occurrence of severe pain,
      depressed mood, and fatigue and help identify patients with severe versus non
      severe symptom clusters. METHODS: Symptoms were assessed at presentation, prior
      to cancer treatment in 599 newly diagnosed lung cancer patients. We applied
      cluster analyses to determine the patients with severe versus non-severe symptom
      clusters of pain, depressed mood, and fatigue. RESULTS: Two homogenous clusters
      were identified. One hundred sixteen patients (19 %) comprised the severe symptom
      cluster, reporting high intensity of pain, depressed mood, and fatigue and 183
      (30 %) patients reported low intensity of these symptoms. Using Bayesian model
      averaging methodology, we found that of the 55 single nucleotide polymorphisms
      assessed, an additive effect of mutant alleles in endothelial nitric oxide
      synthase (-1474 T/A) (posterior probability of inclusion (PPI) = 0.78, odds ratio
      (OR) = 0.54, 95 % credible interval (CI) = (0.31, 0.93)); IL1B T-31C (PPI = 0.72,
      OR = 0.55, 95 % CI = (0.31, 0.97)); TNFR2 Met(196)Arg (PPI = 0.70, OR = 1.85, 95
      % CI = (1.03, 3.36)); PTGS2 exon 10+837T > C (PPI = 0.69, OR = 0.54, 95 % CI =
      (0.28, 0.99)); and IL10RB Lys(47)Glu (PPI = 0.68; OR = 1.74; 95 % CI = (1.04,
      2.92)) were predictive for symptom clusters. CONCLUSIONS: Genetic polymorphisms
      may facilitate identification of high-risk patients and development of
      individualized symptom therapies.

PMID- 23852409
TI  - Replenishable dendrimer-nanoparticle hybrid membranes for sustained release of
      therapeutics.
AB  - We report a versatile hybrid membrane for sustained release therapeutic delivery
      systems. Chemically-directed assembly of a hybrid membrane of nanoparticles and
      dendrimers was integrated with a fluidic delivery device and a refillable drug
      reservoir, providing continuous sustained release. 

PMID- 23852410
TI  - A nanopower bandpass filter for detection of an acoustic signal in a wearable
      breathing detector.
AB  - This paper presents a nanopower programmable bandpass filter suitable to process
      biomedical signals. The filter proves to be very robust to mismatch and process
      variations even when it has been implemented using MOS transistors biased in the
      weak inversion region. The paper analyses design issues associated to matching
      and process variations for the chosen filter topology and constituent
      transconductor block. The design equations justify the choice of both when the
      main constraints are robustness and power. The sixth order, bandpass filter
      prototype consumes 70 nW of power, with a dynamic range greater than 47 dB and
      operates at 1-V power supply. The filter was designed as part of a wearable
      breathing detector but its wide programmability range makes it suitable for many
      other biomedical sensor interfaces that require steep low frequency rejection
      band as well as ultralow power and low voltage operation. 

PMID- 23852408
TI  - Cancer-related fatigue in the elderly.
AB  - PURPOSE: Cancer is a disease of the elderly: 60 % of tumours occur in patients
      aged 65 years or older. Cancer-related fatigue is a common symptom experienced by
      cancer patients and cancer survivors that profoundly affects all aspects of the
      quality of life. Although it has been estimated that up to 70 % of elderly with
      cancer experience fatigue, this symptom is still largely ignored in ageing
      population. METHODS: We performed a systematic review of the literature
      identified by MEDLINE. RESULTS: The relationship between ageing process and
      pathogenesis of cancer-related fatigue is still not fully understood.
      CONCLUSIONS: Ageing is associated with an increased prevalence of chronic
      diseases, decreased functional reserve in multiple organ systems and enhanced
      susceptibility to stress. Ageing and the concomitant presence of a condition of
      frailty may predispose to the presence of fatigue. Nevertheless, only few studies
      have to date specifically assessed the impact of fatigue in the geriatric
      population. Since cancer-related fatigue is a peculiarly debilitating condition
      characteristic of elderly cancer patient population, we suggest the early
      recognition and thorough evaluation of the symptom fatigue, its co-existing
      causes (i.e. anaemia, mood disorders and sleep disturbances) and co-morbidities
      (i.e., endocrine disorders, metabolic, cardiovascular and liver diseases).

PMID- 23852411
TI  - A Low-Power Blocking-Capacitor-Free Charge-Balanced Electrode-Stimulator Chip
      With Less Than 6 nA DC Error for 1-mA Full-Scale Stimulation.
AB  - Large dc blocking capacitors are a bottleneck in reducing the size and cost of
      neural implants. We describe an electrode-stimulator chip that removes the need
      for large dc blocking capacitors in neural implants by achieving precise charge
      balanced stimulation with <6 nA of dc error. For cochlear implant patients, this
      is well below the industry's safety limit of 25 nA. Charge balance is achieved by
      dynamic current balancing to reduce the mismatch between the positive and
      negative phases of current to 0.4%, followed by a shorting phase of at least 1 ms
      between current pulses to further reduce the charge error. On +6 and -9 V rails
      in a 0.7-mum AMI high voltage process, the power consumption of a single channel
      of this chip is 47 muW when biasing power is shared by 16 channels. 

PMID- 23852412
TI  - A low-power integrated bioamplifier with active low-frequency suppression.
AB  - We present in this paper a low-power bioamplifier suitable for massive
      integration in dense multichannel recording devices. This bioamplifier achieves
      reduced-size compared to previous designs by means of active low-frequency
      suppression. An active integrator located in the feedback path of a low-noise
      amplifier is employed for placing a highpass cutoff frequency within the transfer
      function. A very long integrating time constant is achieved using a small
      integrated capacitor and a MOS-bipolar equivalent resistor. This configuration
      rejects unwanted low-frequency contents without the need for input RC networks or
      large feedback capacitors. Therefore, the bioamplifier high-input impedance and
      small size are preserved. The bioamplifier, implemented in a 0.18-mum CMOS
      process, has been designed for neural recording of action potentials, and
      optimised through a transconductance-ef-ficiency design methodology for
      micropower operation. Measured performance and results obtained from in vivo
      recordings are presented. The integrated bioamplifier provides a midband gain of
      50 dB, and achieves an input-referred noise of 5.6 muVrms. It occupies less than
      0.050 mm(2) of chip area and dissipates 8.6 muW. 

PMID- 23852413
TI  - Design and optimization of printed spiral coils for efficient transcutaneous
      inductive power transmission.
AB  - The next generation of implantable high-power neuroprosthetic devices such as
      visual prostheses and brain computer interfaces are going to be powered by
      transcutaneous inductive power links formed between a pair of printed spiral
      coils (PSC) that are batch-fabricated using micromachining technology. Optimizing
      the power efficiency of the wireless link is imperative to minimize the size of
      the external energy source, heating dissipation in the tissue, and interference
      with other devices. Previous design methodologies for coils made of 1-D filaments
      are not comprehensive and accurate enough to consider all geometrical aspects of
      PSCs with planar 3-D conductors as well as design constraints imposed by
      implantable device application and fabrication technology. We have outlined the
      theoretical foundation of optimal power transmission efficiency in an inductive
      link, and combined it with semi-empirical models to predict parasitic components
      in PSCs. We have used this foundation to devise an iterative PSC design
      methodology that starts with a set of realistic design constraints and ends with
      the optimal PSC pair geometries. We have executed this procedure on two design
      examples at 1 and 5 MHz achieving power transmission efficiencies of 41.2% and
      85.8%, respectively, at 10-mm spacing. All results are verified with simulations
      using a commercial field solver (HFSS) as well as measurements using PSCs
      fabricated on printed circuit boards. 

PMID- 23852414
TI  - The advanced health and disaster aid network: a light-weight wireless medical
      system for triage.
AB  - Advances in semiconductor technology have resulted in the creation of miniature
      medical embedded systems that can wirelessly monitor the vital signs of patients.
      These lightweight medical systems can aid providers in large disasters who become
      overwhelmed with the large number of patients, limited resources, and
      insufficient information. In a mass casualty incident, small embedded medical
      systems facilitate patient care, resource allocation, and real-time communication
      in the advanced health and disaster aid network (AID-N). We present the design of
      electronic triage tags on lightweight, embedded systems with limited memory and
      computational power. These electronic triage tags use noninvasive, biomedical
      sensors (pulse oximeter, electrocardiogram, and blood pressure cuff) to
      continuously monitor the vital signs of a patient and deliver pertinent
      information to first responders. This electronic triage system facilitates the
      seamless collection and dissemination of data from the incident site to key
      members of the distributed emergency response community. The real-time collection
      of data through a mesh network in a mass casualty drill was shown to
      approximately triple the number of times patients that were triaged compared with
      the traditional paper triage system. 

PMID- 23852415
TI  - Multimodality sensor system for long-term sleep quality monitoring.
AB  - Sleep monitoring is an important issue and has drawn considerable attention in
      medicine and healthcare. Given that traditional approaches, such as
      polysomnography, are usually costly, and often require subjects to stay overnight
      at clinics, there has been a need for a low-cost system suitable for long-term
      sleep monitoring. In this paper, we propose a system using low-cost multimodality
      sensors such as video, passive infrared, and heart-rate sensors for sleep
      monitoring. We apply machine learning methods to automatically infer a person's
      sleep state, especially differentiating sleep and wake states. This is useful
      information for inferring sleep latency, efficiency, and duration that are
      important for long-term monitoring of sleep quality in healthy individuals and in
      those with a sleep-related disorder diagnosis. Our experiments show that the
      proposed approach offers reasonable performance compared to an existing standard
      approach (i.e., actigraphy), and that multimodality data fusion can improve the
      robustness and accuracy of sleep state detection. 

PMID- 23852416
TI  - Up-regulation of NFATc4 involves in neuronal apoptosis following intracerebral
      hemorrhage.
AB  - Nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcriptional
      factor, is involved in the control about the flow of genetic information and the
      modulation of diverse cellular activities. Accumulating evidence has demonstrated
      that NFATc4 exerted a pro-apoptotic effect in multiple diseases. Here, we
      explored the NFATc4's roles during the pathophysiological processes of
      intracerebral hemorrhage (ICH). An ICH rat model was built and evaluated
      according to behavioral testing. Using Western blot, immunohistochemistry, and
      immunofluorescence, significant up-regulation of NFATc4 was found in neurons in
      brain areas surrounding the hematoma following ICH. Increasing NFATc4 expression
      was found to be accompanied by the up-regulation of Fas ligand (FasL), active
      caspase-8, and active caspase-3, respectively. Besides, NFATc4 co-localized with
      active caspase-3 in neurons, indicating its role in neuronal apoptosis. Our in
      vitro study, using NFATc4 RNA interference in PC12 cells, further confirmed that
      NFATc4 might exert its pro-apoptotic function in neuronal apoptosis through
      extrinsic pathway. Thus, NFATc4 may play a role in promoting the brain secondary
      damage following ICH. 

PMID- 23852417
TI  - Nuclear factor one X regulates Bobby sox during development of the mouse
      forebrain.
AB  - The transcription factor nuclear factor one X (NFIX) plays a central role during
      the development of the neocortex and hippocampus, through the activation of
      astrocyte-specific gene expression and the repression of progenitor-specific
      pathways. However, our understanding of transcriptional targets of NFIX during
      cortical development remains limited. Here, we identify the transcription factor
      Bobby sox (Bbx) as a target for NFI-mediated transcriptional control. BBX is
      expressed within ventricular zone progenitor cells within the developing
      neocortex and hippocampus, and its expression is upregulated in Nfix (-/-) mice.
      Moreover, we reveal that NFIX can repress Bbx promoter-driven expression.
      Collectively, these data suggest that Bbx is a downstream target of NFIX during
      development of the forebrain. 

PMID- 23852418
TI  - Short read (next-generation) sequencing: a tutorial with cardiomyopathy
      diagnostics as an exemplar.

PMID- 23852419
TI  - Cardiovascular effects of aldosterone: insight from adult carriers of
      mineralocorticoid receptor mutations.
AB  - BACKGROUND: High plasma aldosterone has deleterious cardiovascular effects that
      are independent of blood pressure, but the role of the mineralocorticoid receptor
      remains unclear. Renal pseudohypoaldosteronism type 1 is a rare autosomal
      dominant disease caused by NR3C2 loss-of-function mutations, which is
      characterized by renal salt loss and compensatory high renin and aldo secretion.
      We aimed to assess the cardiovascular outcomes in adults carrying NR3C2
      mutations. METHODS AND RESULTS: In this case-control study, 39 NR3C2 mutation
      carriers were compared with sex- and age-paired noncarriers. Patients underwent
      cardiac and vascular ultrasound, cardiac MRI with gadolinium injection,
      measurement of pulse wave velocity, extracellular water, 24-hour ambulatory blood
      pressure, and autonomous nervous system activity. Mutation carriers showed
      increased aldo and renin plasma levels (4.5- and 1.6-fold, respectively;
      P<0.0001), together with increased salt appetite (1.8-fold; P=0.002), with normal
      extracellular water and blood pressure, and no autonomous nervous system
      activation. Cardiac and vascular parameters were not significantly different
      between mutation carriers and noncarriers (no left ventricular remodeling or
      fibrosis, normal left ventricular systolic function, and aorta stiffness). Tissue
      Doppler showed better diastolic left ventricular function in mutation carriers
      (e', P=0.001; E/e', P=0.003). Mutation carriers had significantly more frequent
      history of slow body weight recovery at birth, symptomatic hypotension, and
      miscarriage in women. CONCLUSIONS: Despite life-long increase in plasma
      aldosterone and renin levels, no adverse cardiovascular outcome occurred in
      pseudohypoaldosteronism type 1, but rather an improved diastolic left ventricular
      function. This suggests that the cardiovascular consequences of aldosterone
      excess require full mineralocorticoid receptor signaling. CLINICAL TRIAL
      REGISTRATION: http://www.clinicaltrials.gov; unique identifier: NCT00646828.

PMID- 23852420
TI  - Precursor driven one pot synthesis of wurtzite and chalcopyrite CuFeS2.
AB  - A facile precursor dependent single step, one pot solution based synthesis of
      wurtzite and chalcopyrite polymorphs of CuFeS2 has been developed by reacting a
      Cu(I) thiourea complex with Fe2(SO4)3 and FeCl3 separately in ethylene glycol.
      The phases have been characterized by structural refinements, SEM-EDX, TEM-SAED,
      Raman, UV-Visible spectroscopy and TGA measurements.

PMID- 23852421
TI  - Guidelines and pitfalls for the rehabilitation following hip arthroscopy.
AB  - Rehabilitation guidelines following hip arthroscopy have been presented in the
      literature with common themes consisting of initial protection, restoration of
      lumbo-pelvic stability, neuromuscular re-education, and return to sport training.
      The purpose of this review is to present hip arthroscopy guidelines in 4 phases
      and to address common pitfalls that may delay the rehabilitative process. The
      goal of phase 1 should be to protect healing tissues through activity
      modifications. Phase 2 intends to return the patient to pain-free community
      ambulation without compensation or irritation. A review of hip muscular actions
      during gait is presented to guide exercise progressions during this phase. Phase
      3 should reestablish neuromuscular control through strength and endurance
      training to provide the foundation for return to functional activities or sports
      training progressions. The last phase of rehabilitation is dedicated to
      reestablishing power, speed, agility, and skill for advanced sports and advanced
      functions. 

PMID- 23852423
TI  - Chemoprevention of colon and small intestinal tumorigenesis in APC(min/+) mice by
      SHetA2 (NSC721689) without toxicity.
AB  - The occurrence of intestinal polyps in people at high risk for developing
      colorectal cancer provides an opportunity to test the efficacy of chemoprevention
      agents. In this situation of treating otherwise healthy people, the potential for
      toxicity must be minimal. The small-molecule flexible heteroarotinoid (Flex-Het),
      called SHetA2, has chemoprevention activity in organotypic cultures in vitro and
      lack of toxicity at doses capable of inhibiting xenograft tumor growth in vivo.
      The objective of this study was to evaluate SHetA2 chemoprevention activity and
      toxicity in the APC(min/+) murine model. Oral administration of SHetA2 at 30 and
      60 mg/kg five days per week for 12 weeks significantly reduced development of
      intestinal polyps by 40% to 60% depending on the dose and sex of the treatment
      group. Immunohistochemical and Western blot analysis of polyps showed reduced
      levels of cyclin D1 and proliferating cell nuclear antigen in both SHetA2
      treatment groups. Western blot analysis also showed SHetA2 induction of E
      cadherin, Bax, and caspase-3 cleavage along with reduction in Bcl-2, COX-2, and
      VEGF, consistent with SHetA2 regulation of apoptosis, inflammation, and
      angiogenesis. Neither dose caused weight loss nor gross toxicity in APC(min/+) or
      wild-type littermates. Magnetic resonance imaging (MRI) of cardiac function
      showed no evidence of SHetA2 toxicity. SHetA2 did not alter left ventricular wall
      thickness. In summary, SHetA2 exerts chemoprevention activity without overt or
      cardiac toxicity in the APC(min/+) model. SHetA2 modulation of biomarkers in
      colon polyps identifies potential pharmacodynamic endpoints for SHetA2 clinical
      trials.

PMID- 23852422
TI  - Cheliensisin A inhibits EGF-induced cell transformation with stabilization of p53
      protein via a hydrogen peroxide/Chk1-dependent axis.
AB  - Cheliensisin A (Chel A), a novel styryl-lactone isolated from Goniothalamus
      cheliensis Hu, has been shown to induce apoptosis in human promyelocytic leukemia
      HL-60 cells with Bcl-2 downregulation. Yet, the potential chemopreventive effect
      of Chel A has not been explored. Here, we showed that Chel A treatment with
      various concentrations (0.5, 1.0, 2.0, and 4.0 MUmol/L) for 3 weeks could
      dramatically inhibit EGF-induced cell transformation in Cl41 cells (IC50 ~2.0
      MUmol/L). Also, coincubation of Cl41 cells with Chel A (2.0 and 4.0 MUmol/L) for
      48 hours could induce cell apoptosis in a caspase-3-dependent manner.
      Mechanically, Chel A treatment could result in increased p53 phosphorylation at
      Ser15 and elevated p53 total protein expression. Moreover, we found that p53
      induction by Chel A was regulated at the protein degradation level, but not at
      either the transcription or the mRNA level. Further studies showed that p53
      stabilization by Chel A was mediated via induction of phosphorylation and
      activation of Chk1 protein at Ser345. This notion was substantiated by the
      results that transfection of dominant negative mutant of Chk1 (GFP-Chk1 D130A)
      significantly attenuated the p53 protein expression, cell apoptosis, and
      inhibition of cell transformation by Chel A. Finally, increased hydrogen peroxide
      was found to mediate Chk1 phosphorylation at Ser345, p53 protein induction, cell
      apoptotic induction, and transformation inhibition following Chel A treatment.
      Taken together, our studies identify Chel A as a chemopreventive agent with the
      understanding of the molecular mechanisms involved.

PMID- 23852424
TI  - Psychopathy's influence on the coupling between hypothalamic-pituitary-adrenal
      and -gonadal axes among incarcerated adolescents.
AB  - Conduct disorder (CD) is a heterogeneous diagnosis, leading researchers to
      initiate studies focused on neurobiological mechanisms underlying this disorder.
      One specifier of CD currently considered for inclusion in the DSM-V is callous
      unemotional (CU) traits, a key component of psychopathy. CU traits are thought to
      have neuroendocrine underpinnings, yet little is known about hypothalamic
      pituitary-adrenal (HPA) and -gonadal (HPG) hormones in the context of
      psychopathic traits. The current study sought to identify daily coupling patterns
      between HPA and HPG hormones in order to clarify distinct neurobiological
      underpinning associated with psychopathic/CU traits. Fifty incarcerated
      adolescent males who met criteria for CD were recruited and provided 10 saliva
      samples across 2 days. Participants completed the Psychopathy Checklist Youth
      Version (PCL:YV) and Inventory of Callous Unemotional Traits (ICU) on a third
      day. Diurnal cortisol, testosterone, and DHEA functioning was modeled via
      hierarchical linear modeling. Psychopathy subscales from the measures
      administered were used as predictors of daily coupling patterns between these
      hormones. Results indicated all three hormones were tightly coupled. Further,
      higher PCL-YV interpersonal scores related to greater coupling between all three
      hormones, whereas higher ICU callousness scores related to greater uncoupling of
      testosterone with cortisol and DHEA. The current study is novel in its emphasis
      on testing the coupling of HPA and HPG hormones among incarcerated adolescent
      males. Results suggest that affective and interpersonal psychopathic traits are
      marked by unique HPA- and HPG coupling.

PMID- 23852425
TI  - Training adaptation and heart rate variability in elite endurance athletes:
      opening the door to effective monitoring.
AB  - The measurement of heart rate variability (HRV) is often considered a convenient
      non-invasive assessment tool for monitoring individual adaptation to training.
      Decreases and increases in vagal-derived indices of HRV have been suggested to
      indicate negative and positive adaptations, respectively, to endurance training
      regimens. However, much of the research in this area has involved recreational
      and well-trained athletes, with the small number of studies conducted in elite
      athletes revealing equivocal outcomes. For example, in elite athletes, studies
      have revealed both increases and decreases in HRV to be associated with negative
      adaptation. Additionally, signs of positive adaptation, such as increases in
      cardiorespiratory fitness, have been observed with atypical concomitant decreases
      in HRV. As such, practical ways by which HRV can be used to monitor training
      status in elites are yet to be established. This article addresses the current
      literature that has assessed changes in HRV in response to training loads and the
      likely positive and negative adaptations shown. We reveal limitations with
      respect to how the measurement of HRV has been interpreted to assess positive and
      negative adaptation to endurance training regimens and subsequent physical
      performance. We offer solutions to some of the methodological issues associated
      with using HRV as a day-to-day monitoring tool. These include the use of
      appropriate averaging techniques, and the use of specific HRV indices to overcome
      the issue of HRV saturation in elite athletes (i.e., reductions in HRV despite
      decreases in resting heart rate). Finally, we provide examples in Olympic and
      World Champion athletes showing how these indices can be practically applied to
      assess training status and readiness to perform in the period leading up to a
      pinnacle event. The paper reveals how longitudinal HRV monitoring in elites is
      required to understand their unique individual HRV fingerprint. For the first
      time, we demonstrate how increases and decreases in HRV relate to changes in
      fitness and freshness, respectively, in elite athletes.

PMID- 23852426
TI  - The head and neck symptom checklist(c): an instrument to evaluate nutrition
      impact symptoms effect on energy intake and weight loss.
AB  - PURPOSE: This study aimed to validate the Head and Neck Patient Symptom
      Checklist((c)) (HNSC((c))) by tracing the prevalence and interference with eating
      of nutrition impact symptoms (NIS) over time and by examining relationships among
      NIS included in the HNSC, energy intake, and weight loss. METHODS: Height,
      weight, 3-day diet records, and HNSC((c)) were obtained at baseline,
      posttreatment, and 2.5 month follow-up for 52 treatment-naive head and neck
      cancer (HNC) patients. Relationships among energy intake, weight loss, age, sex,
      treatment, tumor stage, and NIS were evaluated using general estimating equation
      (GEE) modeling. Cumulative hazard (CH) analysis was used to determine the time
      and risk of weight loss. RESULTS: From baseline to posttreatment, 71 % of
      patients had 5 % body weight loss. Despite energy intakes returning to baseline
      levels at follow-up, 88 % of patients continued to lose weight. At posttreatment,
      100 % of patients reported 2 or more NIS (range 2-12); these symptoms were still
      present at follow-up in 83 % of the patients. Univariate GEE analysis
      demonstrated that most NIS predicted energy intake and weight loss, while
      multivariate GEE analysis showed that depression, dysphagia, and sore mouth
      predicted energy intake, and dysphagia and sore mouth predicted weight loss. CH
      analysis showed that NIS accelerated the time and probability of weight loss.
      CONCLUSIONS: The HNSC((c)) is a valid tool for assessing NIS in HNC.
      Identification of NIS may aid in the management of symptoms associated with
      reduced energy intake and weight loss and thus decrease the malnutrition risk in
      HNC patients.

PMID- 23852427
TI  - Preoperative symptoms and postoperative sequelae of intrathoracic neurogenic
      tumors: a single institution's experience.
AB  - OBJECTIVE: Most intrathoracic neurogenic tumors are resected for therapeutic
      diagnosis; many adult tumors are benign. However, few studies have reported the
      preoperative symptoms, postoperative modalities, and sequelae of these tumors. We
      focused on and evaluated the diversity and postoperative prognosis of these
      tumors. METHODS: We assessed 31 consecutive cases of intrathoracic neurogenic
      tumors resected at Tsuchiura Kyodo General Hospital between 1988 and 2012. Two
      cases involved multiple tumors; therefore, complete resection or enucleation was
      performed only in the remaining 29 cases. The patients' clinical records were
      investigated retrospectively. RESULTS: All tumors were benign. Five cases (16.1
      %) presented with preoperative symptoms; 2 cases with non-neurologic symptoms
      (dysphagia due to tumor oppression and a massive hemothorax with
      neurofibromatosis type 1) improved after surgery, but 3 others with neurologic
      symptoms (back pain, hand motor paralysis, and Horner's syndrome) did not. Ten
      cases (32.3 %) presented with postoperative modalities or sequelae. Eight cases
      presented with neurologic sequelae (Horner's syndrome, 4 cases; grip weakness, 3
      cases; hypohidrosis, 3 cases; and hand numbness, 2 cases). All the patients
      presenting with neurologic sequelae had tumors proximal to the first or second
      thoracic vertebra; no tumors proximal to or under the third thoracic vertebra
      caused neurologic sequelae. Severe neurologic sequelae in daily life were
      observed in 2 cases, but they did not radically improve. CONCLUSIONS: While the
      non-neurologic symptoms caused by intrathoracic neurogenic tumors can be resolved
      by resection, the neurologic symptoms may not improve. Tumors proximal to the
      first or second thoracic vertebra can cause postoperative neurologic sequelae.

PMID- 23852428
TI  - Partial lung resection of supernumerary tracheal bronchus combined with pulmonary
      artery sling in an adult: report of a case.
AB  - An adult case of pulmonary resection for repeated infections in a supernumerary
      tracheal bronchus combined with a pulmonary artery sling is reported. A 33-year
      old woman with a pulmonary artery sling was referred for recurrent lung
      infections. Chest computed tomography showed the left pulmonary artery arising
      from the right pulmonary artery and coursing posterior to the trachea. The lung
      parenchyma connected to the tracheal bronchus showed dense opacity and traction
      bronchiectasis. Partial pulmonary resection was performed with an ultrasonically
      activated scalpel after the tracheal bronchus was auto-sutured. The patient's
      postoperative course was uneventful, and she is now in good condition. 

PMID- 23852429
TI  - Incorporating life course theory and social determinants of health into the LEND
      curriculum.
AB  - The goal of this paper is to describe strategies for revising LEND curricula to
      incorporate a stronger focus on life course theory and social determinants of
      health (LCT/SDOH). The Maternal and Child Health Bureau (MCHB) includes a central
      focus on LCT/SDOH and states that a goal of Maternal and Child Health (MCH)
      training is to "Prepare and empower MCH leaders to promote health equity...and
      reduce disparities in health and health care." Two LEND programs engaged in a
      comprehensive process to strengthen LCT/SDOH in their curricula that included
      choosing content and themes and developing instructional strategies congruent
      with MCH Leadership Competencies and with the learning needs of LEND trainees. We
      describe: key elements of LCT/SDOH; the relationship of these to children with
      disabilities and to the MCH Leadership Competencies; LCT/SDOH resources for the
      LEND curriculum; a collaborative curriculum revision process for faculty; and
      LCT/SDOH content and themes for the LEND Curriculum and strategies for
      incorporating them. We present the results of our work in a format that may be
      used by other LEND programs undertaking curriculum revision to incorporate
      LCT/SDOH.

PMID- 23852430
TI  - Intravoxel incoherent motion diffusion-weighted MR imaging of gliomas:
      feasibility of the method and initial results.
AB  - INTRODUCTION: The purpose of this study was to evaluate the feasibility of
      intravoxel incoherent motion (IVIM) imaging and its value in differentiating the
      histologic grade among human gliomas. METHODS: The IVIM model generated
      parametric images for apparent diffusion coefficient ADC, slow diffusion
      coefficient D (or D slow), fast diffusion coefficient D* (or D fast), and
      fractional perfusion-related volume f in 22 patients with gliomas (WHO grade II
      IV) using monopolar Stejskal-Tanner diffusion-weighted imaging (DWI) scheme and
      14 b values ranging from 0 s/mm2 to a maximum of 1,300 s/mm2. A region-of
      interest analysis on the tumor as well as in the white matter was conducted. The
      parameter values were tested for significant differences. The repeatability of
      the measurements was tested by coefficient of variation and Bland-Altman plots.
      RESULTS: D, D*, and f in the high-grade gliomas demonstrated significant
      differences compared to the healthy white matter. D* and f showed a significant
      difference between low- and high-grade gliomas. D tended to be slightly lower in
      the WHO grade II compared to WHO grade III-IV tumors. f and D* demonstrated
      higher coefficients of variation than the ADC and D in tumor. The Bland-Altman
      plots demonstrated satisfactory results without any outliers outside the mean +/-
      1.96 standard deviation. CONCLUSION: The IVIM-fitted post-processing of DWI
      signal decay in human gliomas could show significantly different values of
      fractional perfusion-related volume and fast diffusion coefficient between low-
      and high-grade tumors, which might enable a noninvasive WHO grading in vivo.

PMID- 23852431
TI  - Assessment of the accuracy of a Bayesian estimation algorithm for perfusion CT by
      using a digital phantom.
AB  - INTRODUCTION: A new deconvolution algorithm, the Bayesian estimation algorithm,
      was reported to improve the precision of parametric maps created using perfusion
      computed tomography. However, it remains unclear whether quantitative values
      generated by this method are more accurate than those generated using optimized
      deconvolution algorithms of other software packages. Hence, we compared the
      accuracy of the Bayesian and deconvolution algorithms by using a digital phantom.
      METHODS: The digital phantom data, in which concentration-time curves reflecting
      various known values for cerebral blood flow (CBF), cerebral blood volume (CBV),
      mean transit time (MTT), and tracer delays were embedded, were analyzed using the
      Bayesian estimation algorithm as well as delay-insensitive singular value
      decomposition (SVD) algorithms of two software packages that were the best
      benchmarks in a previous cross-validation study. Correlation and agreement of
      quantitative values of these algorithms with true values were examined. RESULTS:
      CBF, CBV, and MTT values estimated by all the algorithms showed strong
      correlations with the true values (r = 0.91-0.92, 0.97-0.99, and 0.91-0.96,
      respectively). In addition, the values generated by the Bayesian estimation
      algorithm for all of these parameters showed good agreement with the true values
      [intraclass correlation coefficient (ICC) = 0.90, 0.99, and 0.96, respectively],
      while MTT values from the SVD algorithms were suboptimal (ICC = 0.81-0.82).
      CONCLUSIONS: Quantitative analysis using a digital phantom revealed that the
      Bayesian estimation algorithm yielded CBF, CBV, and MTT maps strongly correlated
      with the true values and MTT maps with better agreement than those produced by
      delay-insensitive SVD algorithms.

PMID- 23852433
TI  - Abstracts of EuroEpi 2013 and NordicEpi 2013: non-communicable disease epidemic:
      epidemiology in action. Aarhus, Denmark. August 11-14, 2013.

PMID- 23852432
TI  - Radiation exposure among patients with the highest CT scan utilization in the
      emergency department.
AB  - The risk of cancer from computed tomography (CT) scan radiation is a rising
      concern in the medical field. Our objectives were to determine how many patients
      received more than ten CT scans in an academic emergency department (ED) over the
      course of 7 years and to quantify their radiation exposure and lifetime
      attributable risk of cancer. An electronic chart review was performed at our
      urban academic institution with an annual census of 110,000 patients. All
      patients who underwent a CT scan performed during ED management between the dates
      of January 2001 and December 2007 were identified. Specific predetermined data
      elements (e.g., subject demographics, type of CT scan) were extracted by two
      researchers blinded to hypothesis, using a preformatted data form. After
      identifying patients with more than ten CTs performed during the study period,
      radiation exposure was calculated based on accepted and reported radiation doses
      for the respective anatomic CTs, and lifetime attributable cancer risk was
      calculated based on the seventh report of the Biological Effects of Ionizing
      Radiation (BEIR VII) projections. Over the 7-year study period, 24,393 patients
      received 34,671 CT scans. The vast majority of patients (17,909) received a
      single CT. Twenty-six (0.1 %) patients received more than ten CTs totaling 374
      scans with an average radiation exposure of 83.4 mSv. The maximum lifetime
      attributable risk for any individual in this cohort was 1.7 % above the baseline
      cancer risk. Among those undergoing CT imaging in our ED, high-exposure patients
      (greater than ten scans) constituted a significant minority, while more than one
      in four patients underwent more than one CT scan during the study period. While
      the presumed overall risk of radiation-induced cancer continues to be low, it is
      important for the emergency physician to use clinical knowledge as well as
      concern for the patient when utilizing radiographic imaging. Increasing
      attributable cancer risk may have important public health implications in the
      future, regardless of the low individual risk. 

PMID- 23852434
TI  - A multiplexed luciferase-based screening platform for interrogating cancer
      associated signal transduction in cultured cells.
AB  - Genome-scale interrogation of gene function using RNA interference (RNAi) holds
      tremendous promise for the rapid identification of chemically tractable cancer
      cell vulnerabilities. Limiting the potential of this technology is the inability
      to rapidly delineate the mechanistic basis of phenotypic outcomes and thus inform
      the development of molecularly targeted therapeutic strategies. We outline here
      methods to deconstruct cellular phenotypes induced by RNAi-mediated gene
      targeting using multiplexed reporter systems that allow monitoring of key cancer
      cell-associated processes. This high-content screening methodology is versatile
      and can be readily adapted for the screening of other types of large molecular
      libraries. 

PMID- 23852435
TI  - Astaxanthin reduces hepatic endoplasmic reticulum stress and nuclear factor
      kappaB-mediated inflammation in high fructose and high fat diet-fed mice.
AB  - We recently showed that astaxanthin (ASX), a xanthophyll carotenoid, activates
      phosphatidylinositol 3-kinase pathway of insulin signaling and improves glucose
      metabolism in liver of high fructose-fat diet (HFFD)-fed mice. The aim of this
      study is to investigate whether ASX influences phosphorylation of c-Jun-N
      terminal kinase 1 (JNK1), reactive oxygen species (ROS) production, endoplasmic
      reticulum (ER) stress, and inflammation in liver of HFFD-fed mice. Adult male Mus
      musculus mice were fed either with control diet or HFFD for 15 days. After this
      period, mice in each group were divided into two and administered ASX (2
      mg/kg/day, p.o) in 0.3 ml olive oil or 0.3 ml olive oil alone for the next 45
      days. At the end of 60 days, liver tissue was excised and examined for lipid
      accumulation (Oil red O staining), intracellular ROS production, ER stress, and
      inflammatory markers. Elevated ROS production, lipid accumulation, and increased
      hepatic expression of ER stress markers such as Ig-binding protein, PKR-like ER
      kinase, phosphorylated eukaryotic initiation factor 2alpha, X-box binding protein
      1, activating transcription factor 6, and the apoptotic marker caspase 12 were
      observed in the liver of the HFFD group. ASX significantly reversed these
      changes. This reduction was accompanied by reduced activation of JNK1 and I kappa
      B kinase beta phosphorylation and nuclear factor-kappa B p65 nuclear
      translocation in ASX-treated HFFD mice. These findings suggest that alleviation
      of inflammation and ER stress by ASX could be a mechanism responsible for its
      beneficial effect in this model. ASX could be a promising treatment strategy for
      insulin resistant patients. 

PMID- 23852436
TI  - Clinical outcomes following sublaminar-trimming laminoplasty for extensive lumbar
      canal stenosis.
AB  - PURPOSE: Current surgical approaches for treatment of lumbar canal stenosis are
      often associated with relatively high rates of reoperation and recurrent
      stenosis. We have developed a new approach for treatment of this condition:
      sublaminar-trimming laminoplasty. To describe the surgical approach of sublaminar
      trimming laminoplasty and to assess associated outcomes. METHODS: Patients with
      extensive lumbar canal stenosis who received sublaminar-trimming laminoplasty
      from 2006 to 2008 were considered for inclusion in the study. The surgery
      comprised aspects of laminotomy and laminectomy. The following were assessed
      before surgery and 3 years after surgery: leg and back pain by visual analog
      scale (VAS), extent of disability by Oswestry Disability Index (ODI), severity of
      back pain by Japanese Orthopedic Association Score for Back Pain (JOA), walking
      tolerance, and leg numbness. Complications were noted. RESULTS: A total of 49
      patients were included in the study (mean age 65.6 +/- 10.6 years). VAS leg and
      back pain, ODI, and JOA scores significantly changed from before surgery to 3
      years after surgery (P < 0.001). Mean changes (95 % confidence interval) were 
      6.2 (-6.7, -5.7), -4.3 (-4.8, -3.8), -21.4 (-23.4, -19.5), and 13.4 (12.1, 14.7)
      for leg pain, back pain, ODI, and JOA scores, respectively. Patients experienced
      significant improvements in walking tolerance and leg numbness (P < 0.001). There
      were no instances of recurrent stenosis or postoperative spinal instability.
      Complications included intraoperative dural tear (n = 2), postoperative urinary
      tract infection (n = 2), and inadequate decompression and junctional stenosis
      during follow-up (both n = 1). CONCLUSION: Sublaminar-trimming laminoplasty shows
      promise as an effective treatment for extensive lumbar canal stenosis.

PMID- 23852437
TI  - Letter to the editor concerning: "Antibiotic treatment in patients with chronic
      low back pain and vertebral bone edema (Modic type 1 changes): a double-blind
      randomized controlled trial of efficacy" by Albert HB et al. Eur Spine J (2013)
      22:697-707.

PMID- 23852438
TI  - No conflict of interest?

PMID- 23852439
TI  - Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo
      upon a brief photo-induction.
AB  - Since their discovery, cell-penetrating peptides (CPPs) have provided a novel,
      efficient, and non-invasive mode of transport for various (bioactive) cargos into
      cells. Despite the ever-growing number of successful implications of the CPP
      mediated delivery, issues concerning their intracellular trafficking, significant
      targeting to degradative organelles, and limited endosomal escape are still
      hindering their widespread use. To overcome these obstacles, we have utilized a
      potent photo-induction technique with a fluorescently labeled protein cargo
      attached to an efficient CPP, TP10. In this study we have determined some key
      requirements behind this induced escape (e.g., dependence on peptide-to-cargo
      ratio, time and cargo), and have semi-quantitatively assessed the characteristics
      of the endosomes that become leaky upon this treatment. Furthermore, we provide
      evidence that the photo-released cargo remains intact and functional. Altogether,
      we can conclude that the photo-induced endosomes are specific large complexes
      condensed non-acidic vesicles, where the released cargo remains in its native
      intact form. The latter was confirmed with tubulin as the cargo, which upon photo
      induction was incorporated into microtubules. Because of this, we propose that
      combining the CPP-mediated delivery with photo-activation technique could provide
      a simple method for overcoming major limitations faced today and serve as a basis
      for enhanced delivery efficiency and a subsequent elevated cellular response of
      different bioactive cargo molecules. 

PMID- 23852440
TI  - Plasticity of the Arabidopsis root system under nutrient deficiencies.
AB  - Plant roots show a particularly high variation in their morphological response to
      different nutrient deficiencies. Although such changes often determine the
      nutrient efficiency or stress tolerance of plants, it is surprising that a
      comprehensive and comparative analysis of root morphological responses to
      different nutrient deficiencies has not yet been conducted. Since one reason for
      this is an inherent difficulty in obtaining nutrient-deficient conditions in agar
      culture, we first identified conditions appropriate for producing nutrient
      deficient plants on agar plates. Based on a careful selection of agar
      specifically for each nutrient being considered, we grew Arabidopsis (Arabidopsis
      thaliana) plants at four levels of deficiency for 12 nutrients and quantified
      seven root traits. In combination with measurements of biomass and elemental
      concentrations, we observed that the nutritional status and type of nutrient
      determined the extent and type of changes in root system architecture (RSA). The
      independent regulation of individual root traits further pointed to a
      differential sensitivity of root tissues to nutrient limitations. To capture the
      variation in RSA under different nutrient supplies, we used principal component
      analysis and developed a root plasticity chart representing the overall
      modulations in RSA under a given treatment. This systematic comparison of RSA
      responses to nutrient deficiencies provides a comprehensive view of the overall
      changes in root plasticity induced by the deficiency of single nutrients and
      provides a solid basis for the identification of nutrient-sensitive steps in the
      root developmental program. 

PMID- 23852441
TI  - Teaching an old hormone new tricks: cytosolic Ca2+ elevation involvement in plant
      brassinosteroid signal transduction cascades.
AB  - Brassinosteroids (BRs) are hormones that control many aspects of plant growth and
      development, acting at the cell level to promote division and expansion. BR
      regulation of plant and plant cell function occurs through altered expression of
      many genes. Transcriptional reprogramming downstream from cell perception of this
      hormone is currently known to be mediated by a phosphorylation/dephosphorylation
      ("phosphorelay") cascade that alters the stability of two master transcription
      regulators. Here, we provide evidence that BR perception by their receptor also
      causes an elevation in cytosolic Ca(2+), initiating a Ca(2+) signaling cascade in
      Arabidopsis (Arabidopsis thaliana) cell cytosol. BR-dependent increases in the
      expression of some genes (INDOLE-3-ACETIC ACID-INDUCIBLE1 and PHYTOCHROME B
      ACTIVATION-TAGGED SUPPRESSOR1) were impaired in wild-type plants by a Ca(2+)
      channel blocker and also in the defense-no-death (dnd1) mutant, which lacks a
      functional cyclic GMP-activated cell membrane Ca(2+)-conducting channel.
      Alternatively, mutations that impair the BR phosphorelay cascade did not much
      affect the BR-dependent expression of these genes. Similar effects of the Ca(2+)
      channel blocker and dnd1 mutation were observed on a BR plant growth phenotype,
      deetiolation of the seedling hypocotyl. Further evidence presented in this report
      suggests that a BR-dependent elevation in cyclic GMP may be involved in the
      Ca(2+) signaling cascade initiated by this hormone. The work presented here leads
      to a new model of the molecular steps that mediate some of the cell responses to
      this plant hormone. 

PMID- 23852442
TI  - Basic helix-loop-helix transcription factors JASMONATE-ASSOCIATED MYC2-LIKE1
      (JAM1), JAM2, and JAM3 are negative regulators of jasmonate responses in
      Arabidopsis.
AB  - Jasmonates regulate transcriptional reprogramming during growth, development, and
      defense responses. Jasmonoyl-isoleucine, an amino acid conjugate of jasmonic acid
      (JA), is perceived by the protein complex composed of the F-box protein
      CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM DOMAIN (JAZ) proteins, leading
      to the ubiquitin-dependent degradation of JAZ proteins. This activates basic
      helix-loop-helix-type MYC transcription factors to regulate JA-responsive genes.
      Here, we show that the expression of genes encoding other basic helix-loop-helix
      transcription factors, JASMONATE ASSOCIATED MYC2-LIKE1 (JAM1), JAM2, and JAM3, is
      positively regulated in a COI1- and MYC2-dependent manner in Arabidopsis
      (Arabidopsis thaliana). However, contrary to myc2, the jam1jam2jam3 triple mutant
      exhibited shorter roots when treated with methyl jasmonate (MJ), indicating
      enhanced responsiveness to JA. Our genome-wide expression analyses revealed that
      key jasmonate metabolic genes as well as a set of genes encoding transcription
      factors that regulate the JA-responsive metabolic genes are negatively regulated
      by JAMs after MJ treatment. Consistently, loss of JAM genes resulted in higher
      accumulation of anthocyanin in MJ-treated plants as well as higher accumulation
      of JA and 12-hydroxyjasmonic acid in wounded plants. These results show that JAMs
      negatively regulate the JA responses in a manner that is mostly antagonistic to
      MYC2. 

PMID- 23852443
TI  - Biosensor technology: recent advances in threat agent detection and medicine.
AB  - Biosensors are of great significance because of their capability to resolve a
      potentially large number of analytical problems and challenges in very diverse
      areas such as defense, homeland security, agriculture and food safety,
      environmental monitoring, medicine, pharmacology, industry, etc. The expanding
      role of biosensing in society and a real-world environment has led to an
      exponential growth of the R&D efforts around the world. The world market for
      biosensor devices, according to Global Industry Analysts, Inc., is expected to
      reach $12 billion by 2015. Such expedient growth is driven by several factors
      including medical and health problems, such as a growing population with a high
      risk of diabetes and obesity, and the rising incidence of chronic diseases such
      as heart disease, stroke, cancer, chronic respiratory diseases, tuberculosis,
      etc.; significant problems with environmental monitoring; and of course serious
      challenges in security and military applications and agriculture/food safety. A
      review paper in the biosensor technology area may be structured based on (i) the
      principles of detection, such as the type of transducer platform, bioanalytical
      principles (affinity or kinetic), and biorecognition elements origin/properties
      (i.e. antibodies, enzymes, cells, aptamers, etc.), and (ii) the application area.
      This review follows the latter strategy and focuses on the applications. This
      allows discussion on how different sensing strategies are brought to bear on the
      same problem and highlights advantages/disadvantages of these sensing strategies.
      Given the broad range of biosensor related applications, several particularly
      relevant areas of application were selected for review: biological threat agents,
      chemical threat agents, and medicine. 

PMID- 23852444
TI  - Acute sleep deprivation is associated with increased arterial stiffness in
      healthy young adults.
AB  - BACKGROUND: Arterial stiffness and its hemodynamic consequences are known to be
      associated with increased cardiovascular morbidity and mortality. Pulse wave
      velocity (PWV) and augmentation index (AIx) are noninvasive indicators of the
      arterial stiffness and wave reflection. Sleep deprivation (SD) is known to be
      associated with increased incidence of adverse cardiovascular events. The aim of
      this study was to investigate whether there is an association between acute SD
      and arterial stiffness parameters in healthy adults, which has not been studied
      previously. METHODS: The study population consisted of 42 healthy volunteers (18
      males, mean age 30.0 +/- 4.5 years). Measurements of arterial stiffness were
      carried out by using a Mobil-O-Graph arteriograph system. Arterial stiffness
      measurements were obtained both after a night with regular sleep (RS) and after a
      night with SD. RESULTS: Mean sleep time was significantly lower after the night
      of SD when compared after RS (0.73 +/- 1.39 versus 7.33 +/- 0.52 h, p<0.001).
      Peripheral systolic blood pressure, peripheral pulse pressure, and cardiac output
      were significantly higher after SD when compared after RS (p=0.032, 0.007, and
      0.003, respectively). PWV was significantly higher (5.33 +/- 0.46 versus 5.15 +/-
      0.26 m/s, p=0.001), and AIx was significantly lower (20.5 +/- 11.9 versus 26.0 +/
      8.4 %, p=0.008) after the night of SD when compared after the RS. While PWV was
      significantly higher (p=0.008), and AIx was significantly lower (p=0.039) in male
      subjects, only PWV was significantly higher (p=0.009) in female subjects. Sleep
      time correlated with AIx (p=0.034; r=0.233) and inversely correlated with PWV
      (p=0.044; r=-0.222). CONCLUSION: In the present study, we demonstrated that even
      one night of SD is associated with increased arterial stiffness in healthy
      adults. The present findings suggest that adverse effects of SD on cardiovascular
      system might be at least in part due to increased arterial stiffness which needs
      to be tested with large-scale studies and in the chronic SD setting.

PMID- 23852445
TI  - Outcomes among athletes with arrhythmias and electrocardiographic abnormalities:
      implications for ECG interpretation.
AB  - Electrocardiographic (ECG) aberrations and arrhythmias occur frequently among
      athletes due to normal variants, subclinical cardiac disease or structural and
      electrical remodeling in response to training. It is unclear whether these
      changes are associated with adverse clinical outcomes over time among otherwise
      asymptomatic, healthy athletes. Consensus guidelines have been developed to guide
      the clinician regarding further management of these arrhythmias. The purpose of
      this review is to summarize prospective data regarding cardiovascular outcomes
      related to ECG changes among athletes and compare these findings with current
      guidelines. A review of the literature was conducted using the PubMed database
      (1966--present). Outcomes of interest included documented cardiac symptoms or
      events, such as episodes of cardiac or cerebral hypoperfusion, sudden death or
      prophylactic procedural interventions. Studies were included for analysis if they
      involved (1) athletes with documented, baseline arrhythmias and/or abnormal ECG
      variations; (2) a study design with longitudinal follow-up (designated as >1
      month, to exclude short-term Holter studies); and (3) outcomes that include
      documented cardiac symptoms or events. A total of 33 studies met the above
      criteria, encompassing over 4,200 athletes, with follow-up ranging from 2 months
      to 14.6 years. There were few adverse outcomes among cases of sinus bradycardia
      >30 bpm, sinus pauses <3 s, first-degree atrioventricular (AV) block, second
      degree type I AV block and incomplete right bundle branch block. Results among
      these studies are concordant with guidelines that recommend work-up in the
      setting of cardiac symptoms, history or physical examination indicative of
      cardiac disease, severe sinus bradycardia or AV block that does not resolve with
      exercise or hyperventilation. Outcomes among prospective studies also support
      guidelines that recommend further evaluation for repolarization abnormalities and
      supraventricular tachycardias, including atrial fibrillation, atrial flutter and
      Wolff-Parkinson-White syndrome. Ventricular arrhythmias in the setting of
      structural cardiac disease are associated with an increased risk of adverse
      events, including sudden cardiac death, and warrant special consideration with
      regards to sports eligibility. Findings in this review are limited by a lack of
      control groups, limited assessment of confounding factors (such as performance
      enhancing drugs), and under-representation of women and certain ethnicities.
      Further prospective studies are needed to better characterize the long-term
      outcome of ECG abnormalities among athletes and provide evidence for ECG
      interpretation guidelines.

PMID- 23852446
TI  - Watermelon-like iron nanoparticles: Cr doping effect on magnetism and
      magnetization interaction reversal.
AB  - Cr-doped core-shell iron/iron-oxide nanoparticles (NPs) containing 0, 2, 5, and 8
      at.% of Cr dopant were synthesized via a nanocluster deposition system and their
      structural and magnetic properties were investigated. We observed the formation
      of a sigma-FeCr phase in 2 at.% of Cr doping in core-shell NPs. This is unique
      since it was reported in the past that the sigma-phase forms above 20 at.% of Cr.
      The large coercive field and exchange bias are ascribed to the antiferromagnetic
      Cr2O3 layer formed with the Fe-oxide shell, which also acts as a passivation
      layer to decrease the Fe-oxide shell thickness. The additional sigma-phase in the
      core and/or Cr2O3 in the shell cause the hysteresis loop to appear tight waisted
      near the zero-field axis. The exchange interaction competes with the dipolar
      interaction with the increase of sigma-FeCr grains in the Fe-core. The
      interaction reversal has been observed in 8 at.% of Cr. The observed reversal
      mechanism is confirmed from the Henkel plot and delta M value, and is supported
      by a theoretical watermelon model based on the core-shell nanostructure system. 

PMID- 23852447
TI  - Compact Parkin only: insights into the structure of an autoinhibited ubiquitin
      ligase.
AB  - Mutations in Parkin represent ~50% of disease-causing defects in autosomal
      recessive-juvenile onset Parkinson's disease (AR-JP). Recently, there have been
      four structural reports of autoinhibited forms of this RING-IBR-RING (RBR)
      ubiquitin ligase (E3) by the Gehring, Komander, Johnston and Shaw groups. The
      important advances from these studies set the stage for the next steps in
      understanding the molecular basis for Parkinson's disease (PD).

PMID- 23852448
TI  - Rate enhancement of hexose sugar oxidation on an ethynylpyridine-functionalized
      Pt/Al2O3 catalyst with induced chirality.
AB  - Rate enhancement of the selective oxidation of hexoses was achieved on an
      ethynylpyridine (EPy)-functionalized Pt/Al2O3 catalyst. Host-guest interaction
      between the EPy ligand and a hexose sugar reactant produced a complex with
      induced chirality on the catalyst surface. 

PMID- 23852449
TI  - Nonsteroidal anti-inflammatory drugs suppress cancer stem cells via inhibiting
      PTGS2 (cyclooxygenase 2) and NOTCH/HES1 and activating PPARG in colorectal
      cancer.
AB  - Cancer stem cells (CSCs) play a pivotal role in cancer relapse or metastasis. We
      investigated the CSC-suppressing effect of nonsteroidal anti-inflammatory drugs
      (NSAIDs) and the relevant mechanisms in colorectal cancer. We measured the effect
      of NSAIDs on CSC populations in Caco-2 or SW620 cells using colosphere formation
      and flow cytometric analysis of PROM1 (CD133)(+) CD44(+) cells after indomethacin
      treatment with/without prostaglandin E2 (PGE2) or peroxisome proliferator
      activated receptor gamma (PPARG) antagonist, and examined the effect of
      indomethacin on transcriptional activity and protein expression of NOTCH/HES1 and
      PPARG. These effects of indomethacin were also evaluated in a xenograft mouse
      model. NSAIDs (indomethacin, sulindac and aspirin), celecoxib, gamma-secretase
      inhibitor and PPARG agonist significantly decreased the number of colospheres
      formation compared to controls. In Caco-2 and SW620 cells, compared to controls,
      PROM1 (CD133)(+) CD44(+) cells were significantly decreased by indomethacin
      treatment, and increased by 5-fluorouracil (5-FU) treatment. This 5-FU-induced
      increase of PROM1 (CD133)(+) CD44(+) cells was significantly attenuated by
      combination with indomethacin. This CSC-inhibitory effect of indomethacin was
      reversed by addition of PGE2 and PPARG antagonist. Indomethacin significantly
      decreased CBFRE and increased PPRE transcriptional activity and their relative
      protein expressions. In xenograft mouse experiments using 5-FU-resistant SW620
      cells, the 5-FU treatment combined with indomethacin significantly reduced tumor
      growth, compared to 5-FU alone. In addition, treatment of indomethacin alone or
      combination of 5-FU and indomethacin decreased the expressions of PROM1 (CD133),
      CD44, PTGS2 (cyclooxygenase 2) and HES1, and increased PPARG expression. NSAIDs
      could selectively reduce the colon CSCs and suppress 5-FU-induced increase of
      CSCs via inhibiting PTGS2 (cyclooxygenase 2) and NOTCH/HES1, and activating
      PPARG. 

PMID- 23852450
TI  - Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos.
AB  - Transcriptional enhancers are a primary mechanism by which tissue-specific gene
      expression is achieved. Despite the importance of these regulatory elements in
      development, responses to environmental stresses and disease, testing enhancer
      activity in animals remains tedious, with a minority of enhancers having been
      characterized. Here we describe 'enhancer-FACS-seq' (eFS) for highly parallel
      identification of active, tissue-specific enhancers in Drosophila melanogaster
      embryos. Analysis of enhancers identified by eFS as being active in mesodermal
      tissues revealed enriched DNA binding site motifs of known and putative,
      previously uncharacterized mesodermal transcription factors. Naive Bayes
      classifiers using transcription factor binding site motifs accurately predicted
      mesodermal enhancer activity. Application of eFS to other cell types and
      organisms should accelerate the cataloging of enhancers and understanding how
      transcriptional regulation is encoded in them. 

PMID- 23852451
TI  - A database of Caenorhabditis elegans behavioral phenotypes.
AB  - Using low-cost automated tracking microscopes, we have generated a behavioral
      database for 305 Caenorhabditis elegans strains, including 76 mutants with no
      previously described phenotype. The growing database currently consists of 9,203
      short videos segmented to extract behavior and morphology features, and these
      videos and feature data are available online for further analysis. The database
      also includes summary statistics for 702 measures with statistical comparisons to
      wild-type controls so that phenotypes can be identified and understood by users. 

PMID- 23852452
TI  - In situ sequencing for RNA analysis in preserved tissue and cells.
AB  - Tissue gene expression profiling is performed on homogenates or on populations of
      isolated single cells to resolve molecular states of different cell types. In
      both approaches, histological context is lost. We have developed an in situ
      sequencing method for parallel targeted analysis of short RNA fragments in
      morphologically preserved cells and tissue. We demonstrate in situ sequencing of
      point mutations and multiplexed gene expression profiling in human breast cancer
      tissue sections. 

PMID- 23852453
TI  - Functional labeling of neurons and their projections using the synthetic activity
      dependent promoter E-SARE.
AB  - Identifying the neuronal ensembles that respond to specific stimuli and mapping
      their projection patterns in living animals are fundamental challenges in
      neuroscience. To this end, we engineered a synthetic promoter, the enhanced
      synaptic activity-responsive element (E-SARE), that drives neuronal activity
      dependent gene expression more potently than other existing immediate-early gene
      promoters. Expression of a drug-inducible Cre recombinase downstream of E-SARE
      enabled imaging of neuronal populations that respond to monocular visual
      stimulation and tracking of their long-distance thalamocortical projections in
      living mice. Targeted cell-attached recordings and calcium imaging of neurons in
      sensory cortices revealed that E-SARE reporter expression correlates with sensory
      evoked neuronal activity at the single-cell level and is highly specific to the
      type of stimuli presented to the animals. This activity-dependent promoter can
      expand the repertoire of genetic approaches for high-resolution anatomical and
      functional analysis of neural circuits. 

PMID- 23852454
TI  - Clinical outcome of pediatric choroid plexus tumors: retrospective analysis from
      a single institute.
AB  - BACKGROUND: Choroid plexus tumor is a rare brain tumor with variable clinical
      features according to the histological grade. We reviewed the treatment outcome
      of 23 children, focusing on the biological behavior of the atypical choroid
      plexus papilloma (ACPP) and the current therapeutic strategy in choroid plexus
      carcinoma (CPC). METHODS: The demographics, clinical features, surgical
      treatments, adjuvant therapies, and survival were reviewed. RESULTS: The median
      age at diagnosis was 18 months--55 months for choroid plexus papilloma (CPP), 8
      months for ACPP, and 15 months for CPC. Gross total resections were achieved in
      seven of eight patients with CPP, seven of seven with ACPP, and three of eight
      with CPC. Seven patients with CPC received chemotherapy. Four patients received
      high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell
      transplantation (aPBSCT), and three among them have survived. Four patients with
      CPC received radiotherapy. One CPP patient and one CPC patient underwent
      radiosurgery. All CPP and ACPP patients have survived. The overall survival rate
      of the CPC patients was 62.5% in the first year and 42.9% in the second year. The
      progression-free survival rate of the CPC patients was 50% in the first year and
      0% in the second year. Seven patients underwent permanent cerebrospinal fluid
      diversion surgery because of hydrocephalus or subdural effusion. CONCLUSION: CPP
      and ACPP were surgically curable. Multi-modal treatments are necessary in the
      management of CPC with poor prognosis. HDCT and aPBSCT may be important to treat
      infants for whom radiotherapy is limited. Hydrocephalus and subdural effusion
      should be resolved with appropriate management.

PMID- 23852455
TI  - Stimulation of phagocyte adhesion to endothelial cells by modified VLDL and HDL
      requires scavenger receptor BI.
AB  - Hyperglycemia- and oxidative stress-induced modification of circulating
      lipoproteins is being increasingly recognized as an important pathogenetic factor
      for diabetic cardiovascular damages. This study was designed to investigate the
      impact of modified very low-density lipoprotein and high-density lipoprotein on
      phagocyte adhesion to endothelial cells and the involvement of scavenger receptor
      class B type 1 (SR-BI) in this process. Native lipoproteins were isolated by
      density gradient ultracentrifugation and in vitro glycoxidative or oxidative
      modification was performed in the presence of glucose or sodium hypochlorite,
      respectively. One hour co-incubation experiments with lipoproteins, freshly
      prepared polymorphonuclear leukocytes (PMN), and venous endothelial cells (HUVEC)
      were performed in the presence or absence of different scavenger receptors and
      signal transduction inhibitors. PMN adhesion to HUVEC was quantified
      fluorimetrically. We demonstrated that oxidized and glycoxidized lipoproteins
      promote adhesion of PMN to HUVEC from 1.5- to 2.5-fold with oxidized lipoproteins
      having the greatest effect. Treatment with the highly specific SR-BI inhibitor,
      BLT-1 produced substantial reduction of lipoprotein-induced adhesion to
      endothelial cells. Native and modified lipoproteins recruited extracellular
      signal-regulated kinase (ERK 1/2), p38 mitogen-activated protein kinase, and
      Janus kinase 2 as downstream signaling pathways for adhesion. From this study, it
      could be concluded that modification of lipoproteins plays a crucial role in
      atherosclerotic progression and SR-BI may be considered as a potential
      therapeutic target for the prevention of diabetic cardiovascular complications.

PMID- 23852456
TI  - Electroencephalogram patterns in infants of depressed mothers.
AB  - Electroencephalogram (EEG) patterns may reflect a vulnerability to depression. In
      an effort to understand their earliest origin, we examined their stability and
      consistency and their associations with perinatal depressive symptoms. Depressive
      symptoms were measured prospectively throughout the perinatal period in 83 women
      with histories of depression and/or anxiety. Infant's EEG was recorded during
      baseline, feeding, and play at 3 and 6 months of age. Prenatal and postpartum
      depressive symptoms interacted significantly to predict 3- and 6-month-olds' EEG
      asymmetry scores. Asymmetry scores were consistent across contexts, except from
      baseline to feeding and play at 6 months, and stable across ages, except during
      feeding. Changes in depressive symptoms across ages were not associated with
      changes in infant EEG. Findings highlight the importance of considering both
      prenatal and postpartum depressive symptoms in the prediction of infant EEG, as
      well as the need to consider context to understand stability of infant EEG
      patterns.

PMID- 23852457
TI  - "I know your pain": proximal and distal predictors of pain detection accuracy.
AB  - The aim of this research was to examine predictors of pain detection accuracy. In
      Study 1 (n = 160, undergraduates), the predictors were distal factors (empathy,
      emotion recognition, family history, and past experiences with pain), and in
      Study 2 (n = 104, undergraduates), the predictor was a proximal factor (an
      experimentally induced experience of pain). Results showed that having past and
      an immediate experience with pain as well as being more empathic were associated
      with higher pain detection accuracy scores. Men were more accurate at detecting
      pain than women in both studies. Our findings contribute to a growing literature
      on pain detection and empathy. 

PMID- 23852458
TI  - Loss of MTSS1 expression is an independent prognostic factor for Hilar
      cholangiocarcinoma.
AB  - Metastasis suppressor 1 (MTSS1) is a novel metastasis suppressor gene in a
      variety of cancers. This study aimed to detect MTSS1 expression in normal and
      cancerous tissue specimens from Chinese patients with hilarcholangiocarcinoma to
      determine the association with clinicopathological parameters and survival.
      Tissue microarrays containing normal and tumor specimens were constructed using
      paraffin blocks from 61 patients for immunohistochemical analysis of MTSS1
      expression. A subgroup of these tissues was verified by Western blot analysis.
      MTSS1 protein was expressed in 24 of 61 cases (39.3 %) of tumor tissues, compared
      to that in 22 of 26 (84.6 %) of non-neoplastic bile duct epithelium and in 26 of
      26 (100 %) of adjacent normal liver cells. Loss of MTSS1 expression was
      associated with lymph node metastases of cholangiocelluarcarcinoma and
      tumorcellde-differentiation.MTSS1 expression inversely associated with tumor
      recurrence and overall survival of the patients by univariate and multivariate
      analyses. MTSS1 expression was significantly decreased in human
      hilarcholangiocarcinoma and lost MTSS1 expression was associated with pooroverall
      survival and tumor recurrences in cholangiocarcinoma patients. Thus, MTSS1
      expression represents an independent predictor for tumor recurrence and overall
      survival in patients with cholangiocarcinoma.

PMID- 23852459
TI  - The incidence of EGFR-activating mutations in bone metastases of lung
      adenocarcinoma.
AB  - Poor prognosis of lung adenocarcinoma is associated with early occurrence of
      distant metastases. This type of non-small-cell lung carcinoma more frequently
      involves EGFR gene abnormalities, which determine the efficacy of EGFR tyrosine
      kinase inhibitor therapies (EGFR TKIs). It is probable that genetic abnormalities
      present in primary tumor will also be present in metastases. Unfortunately little
      is known about the incidence of these mutations in the metastases and about the
      effectiveness of molecularly targeted therapy in such patients. Formalin-fixed,
      paraffin-embedded tumor tissue was prepared from 431 samples of primary
      adenocarcinoma, 61 of adenocarcinoma central nervous system (CNS) metastases and
      8 of adenocarcinoma bone metastases. The presence of exon 19 deletions was
      examined using the PCR technique and amplified PCR product fragment length
      analysis. The ASP-PCR technique was used to evaluate the L858R substitutions in
      exon 21, and the results were analyzed using ALF Express II sequencer. In the
      adenocarcinoma metastases to bone obtained from 8 patients, deletions in exon 19
      of the EGFR gene were revealed in 3 smoking men and one non-smoking woman, while
      L858R substitution in exon 21 was found in one smoking woman and one man of
      unknown smoking status. The incidence of EGFR gene mutations in the bone
      metastases was 75%, in the primary adenocarcinoma--12.8%, and in the
      adenocarcinoma metastases to CNS--14.75%. Five patients with EGFR gene mutation
      revealed in bone metastases were treated with EGFR TKIs; the majority of them had
      a satisfactory response to therapy.

PMID- 23852460
TI  - Cerebral near-infrared spectroscopy correlates to vital parameters during
      cardiopulmonary bypass surgery in children.
AB  - Near-infrared spectroscopy (NIRS) can monitor changes in cerebral regional oxygen
      saturation (rSO2) and tissue hemoglobin content (HbT). The relation between
      cerebral NIRS readings and vital parameters has not been analyzed before at a
      fine temporal scale. This study analyzed this relation during cardiopulmonary
      bypass (CPB) surgery in 10 children (0-9 years, 1,770 min of data records) by
      using a novel random-coefficient model. The analysis indicated that a small
      number of patients is sufficient for obtaining significant results with this
      model. Changes of vital parameters explained 84.7 % of rSO2 changes and 90.7 % of
      HbT changes. Cerebral rSO2 correlated positively with perfusion pressure and
      inversely with body temperature (P < 0.05). Cerebral HbT correlated positively
      with perfusion pressure, central venous pressure, and temperature and inversely
      with arterial oxygen saturation (P < 0.05). During hypothermic circulatory
      arrest, the half-life of the exponential rSO2 decay correlated to the rSO2
      reserve (P = 0.016). In conclusion, NIRS readings of cerebral hemoglobin content
      and tissue oxygen saturation correlate well to vital parameters during CPB
      surgery in children. NIRS may therefore become a monitoring device for the
      neuroprotective optimization of those vital parameters. 

PMID- 23852461
TI  - Systolic right-ventricular function impairment in healthy children after
      endurance stress.

PMID- 23852462
TI  - Factors associated with recoarctation after surgical repair of coarctation of the
      aorta by way of thoracotomy in young infants.
AB  - Echocardiography is the mainstay of preoperative arch imaging in infants with
      coarctation of the aorta. In simple coarctation, repair by way of sternotomy or
      thoracotomy is often determined by echocardiographic transverse arch
      measurements. The degree of arch hypoplasia that is prohibitive to repair by way
      of thoracotomy is unknown. Clinical predictors of recoarctation are also unknown.
      Demographic, echocardiographic (transverse arch and aortic measurements),
      operative, and postoperative data of infants <90 days old with simple coarctation
      repaired by way of thoracotomy between February 2005 and November 2011 were
      evaluated. Recoarctation was defined as surgical or catheter reintervention after
      hospital discharge. Eighty-four infants underwent coarctation repair at median
      age of 12 (range 1-85) days with median follow-up of 12.3 (range 0.5-71.9)
      months. The seven (8 %) infants with recoarctation underwent balloon angioplasty.
      In multivariable analysis, only greater postoperative Doppler peak velocity
      [1.13, confidence interval (CI) 1.04-1.23] and greater sinotubular junction z
      score (hazard ratio 4.19, CI 1.47-11.95) independently predicted coarctation.
      Doppler peak velocity >2.12 m/s had sensitivity of 63 % and specificity of 83 %
      of predicting recoarctation, and ST junction z-score >-0.93 had sensitivity of
      100 % and specificity of 58 %. No transverse arch dimensions were independently
      associated with recoarctation. Infants with transverse arch z-score as low as 
      2.8 underwent successful repair by way of thoracotomy. No clinical predictors
      were significant. 

PMID- 23852463
TI  - Contemporary management of frontal sinus mucoceles: a meta-analysis.
AB  - OBJECTIVES/HYPOTHESIS: To analyze trends in the surgical management of frontal
      and fronto-ethmoid mucoceles through meta-analysis. STUDY DESIGN: Meta-analysis
      and case series. METHODS: A systematic literature review on surgical management
      of frontal and fronto-ethmoid mucoceles was conducted. Studies were divided into
      historical (1975-2001) and contemporary (2002-2012) groups. A meta-analysis of
      these studies was performed. The historical and contemporary cohorts were
      compared (surgical approach, recurrence, and complications). To study evolution
      in surgical management, a senior surgeon's experience over 28 years was analyzed
      separately. RESULTS: Thirty-one studies were included for meta-analysis. The
      historical cohort included 425 mucoceles from 11 studies. The contemporary cohort
      included 542 mucoceles from 20 studies. More endoscopic techniques were used in
      the contemporary versus historical cohort (53.9% vs. 24.7%; P = <0.001). In the
      authors' series, a higher percentage was treated endoscopically (82.8% of 122
      mucoceles). Recurrence (P = 0.20) and major complication (P = 0.23) rates were
      similar between cohorts. Minor complication rates were superior for endoscopic
      techniques in both cohorts (P = 0.02 historical; P = <0.001 contemporary). In the
      historical cohort, higher recurrence was noted in the external group (P = 0.03).
      CONCLUSIONS: Results from endoscopic and open approaches are comparable. Although
      endoscopic techniques are being increasingly adopted, comparison with our series
      shows that more cases could potentially be treated endoscopically. Frequent use
      of open approaches may reflect efficacy, or perhaps lack of expertise and
      equipment required for endoscopic management. Most contemporary authors favor
      endoscopic management, limiting open approaches for specific indications
      (unfavorable anatomy, lateral disease, and scarring). LEVEL OF EVIDENCE: N/A.

PMID- 23852464
TI  - Eight Zn(II) coordination networks based on flexible 1,4-di(1H-imidazol-1
      yl)butane and different dicarboxylates: crystal structures, water clusters, and
      topologies.
AB  - Eight new Zn(II) coordination polymers based on flexible 1,4-di(1H-imidazol-1
      yl)butane and different dicarboxylates, [Zn(dimb)(suc).2DMF]n (1),
      [Zn(dimb)(mbda).3H2O]n (2), [Zn(dimb)(adip).DMF.2H2O]n (3),
      [Zn(dimb)(pma).2.5H2O]n (4), [Zn2(dimb)(tha)2(H2O)]n (5), [Zn(dimb)(chda).2H2O]n
      (6), [Zn(dimb)(obda).DMF]n (7), [Zn(dimb)(tdga).CH3OH]n (8) (dimb = 1,4-di(1H
      imidazol-1-yl)butane, H2suc = succinic acid, H2mbda = m-benzenediacetic acid,
      H2adip = adipic acid, H2pma = pimelic acid, H2tha = thiophene-2,5-dicarboxylic
      acid, H2chda = 1,4-cyclohexanedicarboxylic acid, H2obda = o-benzenediacetic acid,
      H2tdga = thiodiglycolic acid; DMF = N,N'-dimethylformamide), have been
      synthesized and structurally characterized by single-crystal X-ray diffraction
      analyses, and further characterized by infrared spectra (IR), elemental analyses,
      powder X-ray diffractions (PXRD) and thermogravimetric analyses (TGA). Single
      crystal X-ray diffraction analysis reveals that 1, 2, 4, 7 and 8 are 2D wavy 4(4)
      sql networks with different dimensions of quadrilateral window units, depending
      on the conformation and length of dimb and dicarboxylates. Complex 3 is a 2D a
      6(3)-hcb network incorporating a [Zn2(dimb)2] cyclic subunit. In complex 5,
      Zn(II) centers as 3-connected node are linked by dimb and tha to form a 3D 8-fold
      interpenetrating ThSi2 network. Complex 6 is a 4-connected noninterpenetrating
      cds network. Interestingly, an infinite T4(2)6(2) water tape and a D2h cyclic
      water tetramer are also found in complexes 2 and 3, respectively. In 1-8, all
      Zn(II) centers are located in a four-coordinated environment, and dimb and
      dicarboxylates are 2-connected linkers, but networks with diverse topologies are
      built, which indicates the linkage of central metal ion, the conformation of dimb
      and dicarboxylate have important influences on the resulting structures.
      Furthermore, the solid-state photoluminescence properties of the 1-8 were
      investigated at 298 and 77 K.

PMID- 23852465
TI  - Hydrogen sulfide ameliorates lead-induced morphological, photosynthetic,
      oxidative damages and biochemical changes in cotton.
AB  - Poisonous lead (Pb), among heavy metals, is a potential pollutant that readily
      accumulates in soils and thus adversely affects physiological processes in
      plants. We have evaluated how exogenous H2S affects cotton plant physiological
      attributes and Pb uptake under Pb stress thereby understanding the role of H2S in
      physiological processes in plants. Two concentrations (0 and 200 MUM) of H2S
      donor sodium hydrosulfide (NaHS) were experimented on cotton plants under Pb
      stress (0, 50, and 100 MUM). Results have shown that Pb stress decreased plant
      growth, chlorophyll contents, SPAD value, photosynthesis, antioxidant activity.
      On the other hand, Pb stress increased the level of malondialdehyde (MDA),
      electrolyte leakage (EL), and production of H2O2 and uptake of Pb contents in all
      three parts of plant, viz. root, stem, and leaf. Application of H2S slightly
      increased plant growth, chlorophyll contents, SPAD value, photosynthesis, and
      antioxidant activity as compared to control. Hydrogen sulfide supply alleviated
      the toxic effects of lead on plant growth, chlorophyll contents, SPAD value,
      photosynthesis, and antioxidant activity in cotton plants. Hydrogen sulfide also
      reduced MDA, EL, and production of H2O2 and endogenous Pb levels in the three
      mentioned plant parts. On the basis of our results, we conclude that H2S has
      promotive effects which could improve plant survival under Pb stress. 

PMID- 23852466
TI  - Photosynthesis mediated decrease in cadmium translocation protect shoot growth of
      Oryza sativa seedlings up on ammonium phosphate-sulfur fertilization.
AB  - Cadmium (Cd) stress responses in seedlings of two Indian rice cultivars, MTU 7029
      and MO 16 were investigated under ammonium-based fertilizer amendment. Cd
      translocation was reduced by fertilizer treatment. An increase in the production
      of organic acids as well as nitrogenous compounds and maintenance of nutrient
      status were implicated for decrease in Cd translocation which in turn promoted
      shoot growth. Fertilizer treatment increased photosynthetic pigments and activity
      of antioxidant enzymes that ensured steady photosynthetic rate during Cd stress.
      MO 16 showed Cd exclusion characteristics when compared with MTU 7029.
      Photosynthesis performance of MO 16 was not affected by Cd treatments. These
      findings suggest that photosynthesis influenced decrease in Cd translocation
      enhanced shoot growth of seedlings during ammonium phosphate-sulfur fertilizer
      supplementation. 

PMID- 23852467
TI  - Metal accumulation in the greentail prawn, Metapenaeus bennettae, in Sydney and
      Port Hacking estuaries, Australia.
AB  - Metal concentrations of the inshore greentail prawn, Metapenaeus bennettae, and
      surface sediments from locations within Sydney estuary and Port Hacking
      (Australia) were assessed for bioaccumulation and contamination. The current
      study aimed to assess metal concentrations in prawn tissue (tail muscle,
      exoskeleton, hepatopancreas and gills), relate whole body prawn tissue metal
      concentrations to sediment metal concentrations and animal size, as well as
      assess prawn consumption as a risk to human health. Metal concentrations were
      highest in sediment and prawns from contaminated locations (Iron Cove, Hen and
      Chicken Bay and Lane Cove) in Sydney estuary compared with the reference estuary
      (Port Hacking). Concentrations in sediments varied considerably between sites and
      between metals (As, Cd, Cr, Cu, Ni, Pb and Zn), and although concentrations
      exceeded Interim Sediment Quality Guideline-Low values, metals (As, Cd, Cr, Cu,
      Ni, Pb and Zn) were below Australian National Health and Medical Research Council
      human consumption guidelines in prawn tail muscle tissue. Metal concentrations in
      prawn tail muscle tissue were significantly different (p <= 0.05) amongst
      locations for Pb, Zn and Cd, and metal concentrations were generally highest in
      gills tissue, followed by the hepatopancreas, exoskeleton and tail muscle. The
      exoskeleton contained the highest Sr concentration; the hepatopancreas contained
      the highest As, Cu and Mo concentrations; and the gills contained the highest Al,
      Cr, Fe and Pb concentrations. Concentrations of Pb, As and Sr were significantly
      different (p <= 0.05) between size groups amongst locations. 

PMID- 23852468
TI  - An efficient and robust method for analyzing population pharmacokinetic data in
      genome-wide pharmacogenomic studies: a generalized estimating equation approach.
AB  - Powerful array-based single-nucleotide polymorphism-typing platforms have
      recently heralded a new era in which genome-wide studies are conducted with
      increasing frequency. A genetic polymorphism associated with population
      pharmacokinetics (PK) is typically analyzed using nonlinear mixed-effect models
      (NLMM). Applying NLMM to large-scale data, such as those generated by genome-wide
      studies, raises several issues related to the assumption of random effects as
      follows: (i) computation time: it takes a long time to compute the marginal
      likelihood; (ii) convergence of iterative calculation: an adaptive Gauss-Hermite
      quadrature is generally used to estimate NLMM; however, iterative calculations
      may not converge in complex models; and (iii) random-effects misspecification
      leads to slightly inflated type-I error rates. As an alternative effective
      approach to resolving these issues, in this article, we propose a generalized
      estimating equation (GEE) approach for analyzing population PK data. In general,
      GEE analysis does not account for interindividual variability in PK parameters;
      therefore, the usual GEE estimators cannot be interpreted straightforwardly, and
      their validities have not been justified. Here, we propose valid inference
      methods for using GEE even under conditions of interindividual variability and
      provide theoretical justifications of the proposed GEE estimators for population
      PK data. In numerical evaluations by simulations, the proposed GEE approach
      exhibited high computational speed and stability relative to the NLMM approach.
      Furthermore, the NLMM analysis was sensitive to the misspecification of the
      random-effects distribution, and the proposed GEE inference is valid for any
      distributional form. We provided an illustration by using data from a genome-wide
      pharmacogenomic study of an anticancer drug.

PMID- 23852469
TI  - Remembering Professor Mamoru Tamura.
AB  - Dr. Mamoru Tamura (1943-2011) was the honorary president of the ISOTT 2008
      meeting in Sapporo, Japan, and has made numerous contributions to biomedical
      optics and functional near-infrared spectrometry. This chapter briefly describes
      Dr. Tamura's scientific achievements and contributions to the society based on
      the "Memorial lecture about Mamoru Tamura's contributions to biomedical optics"
      in ISOTT 2012 in Bruges, Belgium. 

PMID- 23852470
TI  - Increased kidney metabolism as a pathway to kidney tissue hypoxia and damage:
      effects of triiodothyronine and dinitrophenol in normoglycemic rats.
AB  - Intrarenal tissue hypoxia is an acknowledged common pathway to end-stage renal
      disease in clinically common conditions associated with development of chronic
      kidney disease, such as diabetes and hypertension. In diabetic kidneys, increased
      oxygen metabolism mediated by mitochondrial uncoupling results in decreased
      kidney oxygen tension (PO2) and contributes to the development of diabetic
      nephropathy. The present study investigated whether increased intrarenal oxygen
      metabolism per se can cause intrarenal tissue hypoxia and kidney damage,
      independently of confounding factors such as hyperglycemia and oxidative stress.
      Male Sprague-Dawley rats were untreated or treated with either triiodothyronine
      (T3, 10 g/kg bw/day, subcutaneously for 10 days) or the mitochondria uncoupler
      dinitrophenol (DNP, 30 mg/kg bw/day, oral gavage for 14 days), after which in
      vivo kidney function was evaluated in terms of glomerular filtration rate (GFR,
      inulin clearance), renal blood flow (RBF, Transonic, PAH clearance), cortical PO2
      (Clark-type electrodes), kidney oxygen consumption (QO2), and proteinuria.
      Administration of both T3 and DNP increased kidney QO2 and decreased PO2 which
      resulted in proteinuria. However, GFR and RBF were unaltered by either treatment.
      The present study demonstrates that increased kidney metabolism per se can cause
      intrarenal tissue hypoxia which results in proteinuria. Increased kidney QO2 and
      concomitantly reduced PO2 may therefore be a mechanism for the development of
      chronic kidney disease and progression to end-stage renal disease. 

PMID- 23852471
TI  - Hypoxia-induced cerebral angiogenesis in mouse cortex with two-photon microscopy.
AB  - To better understand cellular interactions of the cerebral angiogenesis induced
      by hypoxia, a spatiotemporal dynamics of cortical microvascular restructuring
      during an exposure to continuous hypoxia was characterized with in vivo two
      photon microscopy in mouse cortex. The mice were prepared with a closed cranial
      window over the sensory-motor cortex and housed in 8-9 % oxygen room for 2-4
      weeks. Before beginning the hypoxic exposure, two-photon imaging of cortical
      microvasculature was performed, and the follow-up imaging was conducted weekly in
      the identical locations. We observed that 1-2 weeks after the onset of hypoxic
      exposure, a sprouting of new vessels appeared from the existing capillaries. An
      average emergence rate of the new vessel was 15 vessels per unit volume (mm(3)).
      The highest emergence rate was found in the cortical depths of 100-200 MUm,
      indicating no spatial uniformity among the cortical layers. Further, a leakage of
      fluorescent dye (sulforhodamine 101) injected into the bloodstream was not
      detected, suggesting that the blood-brain barrier (BBB) was maintained. Future
      studies are needed to elucidate the roles of perivascular cells (e.g., pericyte,
      microglia, and astroglia) in a process of this hypoxia-induced angiogenesis, such
      as sprouting, growth, and merger with the existing capillary networks, while
      maintaining the BBB. 

PMID- 23852472
TI  - Reduction of cytochrome C oxidase during vasovagal hypoxia-ischemia in human
      adult brain: a case study.
AB  - Near-infrared spectroscopy (NIRS)-derived measurement of oxidized cytochrome c
      oxidase concentration ([oxCCO]) has been used as an assessment of the adequacy of
      cerebral oxygen delivery. We report a case in which a reduction in conscious
      level was associated with a reduction in [oxCCO]. Hypoxaemia was induced in a 31
      year-old, healthy male subject as part of an ongoing clinical study. Midway
      through the hypoxaemic challenge, the subject experienced an unexpected vasovagal
      event with bradycardia, hypotension and reduced cerebral blood flow (middle
      cerebral artery blood flow velocity decrease from 70 to 30 cm s(-1)) that induced
      a brief reduction in conscious level. An associated decrease in [oxCCO] was
      observed at 35 mm (-1.6 MUM) but only minimal change (-0.1 MUM) at 20-mm source
      detector separation. A change in optical scattering was observed, but path length
      remained unchanged. This unexpected physiological event provides an unusual
      example of a severe reduction in cerebral oxygen delivery and is the first report
      correlating change in clinical status with changes in [oxCCO]. 

PMID- 23852473
TI  - Increased HIF-1alpha and HIF-2alpha accumulation, but decreased microvascular
      density, in chronic hyperoxia and hypercapnia in the mouse cerebral cortex.
AB  - The partial pressure of oxygen in the brain parenchyma is tightly controlled, and
      normal brain function is delicately sensitive to continuous and controlled oxygen
      delivery. The objective of this study was to determine brain angiogenic adaptive
      changes during chronic normobaric hyperoxia and hypercapnia in mice. Four-month
      old C56BL/6 J mice were kept in a normobaric chamber at 50 % O2 and 2.5 % CO2 for
      up to 3 weeks. Normoxic littermates were kept adjacent to the chamber and
      maintained on the same schedule. Physiological variables were measured at time
      points throughout the 3 weeks or when the mice were sacrificed. Freshly collected
      or fixed brain specimens were analyzed by Western blot analysis and
      immunohistochemistry (IHC). We found significant accumulation of hypoxia
      inducible factors 1alpha and 2alpha (HIF-1alpha and HIF-2alpha) and increased
      expression of erythropoietin (EPO), cyclooxygenase-2 (COX-2), and angiopoietin-2
      (Ang-2) in hyperoxia and hypercapnia. Conversely, vascular endothelial growth
      factor (VEGF), and VEGF receptor-2 (KDR/Flk-1), peroxisome proliferator-activated
      receptor gamma coactivator 1-alpha (PGC-1alpha), and prolyl hydroxylase-2 (PHD-2)
      expressions were decreased in hyperoxia and hypercapnia. Capillary density was
      significantly diminished by the end of the 3rd week of hyperoxia and hypercapnia
      as compared to control. We conclude that HIF-independent mechanisms contribute to
      brain capillary density modulation that is continuously adjusted in accordance
      with tissue oxygen tension. 

PMID- 23852474
TI  - Oxygen delivery: the principal role of the circulation.
AB  - Autoregulation of blood flow to most individual organs is well known. The balance
      of oxygen supply relative to the rate of oxygen consumption ensures normal
      function. There is less reserve as regards oxygen supply than for any other
      necessary metabolite or waste product so oxygen supply is flow dependent. Reduced
      rate of supply compromises tissue oxygenation long before any other substance.
      The present report reiterates evidence from earlier studies demonstrating that
      the rate of oxygen delivery (DO2), for most individual tissues, is well sustained
      at a value bearing a ratio to oxygen consumption (VO2) which is specific for the
      organ concerned. For the brain DO2 is sustained at approximately three times the
      rate of oxygen consumption and for exercising skeletal muscle (below the
      anaerobic threshold), a ratio close to 1.5. The tissue-specific ratios are
      sustained in the face of alterations in local VO2 and lowered arterial oxygen
      content (CaO2). Tolerance varies between different organs. Hence, the role of the
      circulation is predominantly one of ensuring an adequate supply of oxygen. The
      precise values of the individual tissue DO2:VO2 ratios apply within physiological
      ranges which require further investigation. 

PMID- 23852476
TI  - Simultaneous monitoring of brain and skin oxygenation during haemorrhagic shock
      in piglets.
AB  - Phosphorescence quenching and visible lightguide spectrophotometry were used to
      measure brain cortex oxygen partial pressure and skin oxygen saturation,
      respectively, during stepwise haemorrhage and re-transfusion in four 4-7-day-old
      anaesthetised piglets. In three cases, the effect of administration of adrenalin
      (epinephrine) was investigated. Brain cortex partial pressure was measured using
      a conventional phosphorescence pO2 probe (bclocpO2) and using a self-contained
      phosphorescence microsensor (bcmicropO2). Peripheral tissue oxygen saturation was
      measured on the skin of the abdomen (abSsO2) and the distal right foreleg
      (flSsO2) using visible lightguide spectrophotometry. Haemorrhage of 65 ml reduced
      mean arterial blood pressure (MABP) from 75.5 +/- 11.0 mmHg (mean +/- standard
      deviation) to 42 +/- 2.6 mmHg. Mean bclocpO2 fell from 30.1 +/- 3.1 to 13.1 +/-
      2.5 mmHg and mean bcmicropO2 fell from 33.8 +/- 11.4 to 13.3 +/- 9.5 mmHg. abSsO2
      and flSsO2 values fell from 47.4 +/- 8.1 % and 43.6 +/- 10.9 %, respectively, to
      21.9 +/- 5.5 % and 23.8 +/- 14.0 %. Infusion of adrenalin produced a mean
      transient increase in MABP to 137 +/- 2.6 mmHg, falling to 75.7 +/- 16.3 mmHg
      within 3 min. bclocpO2 also increased to 24.1 +/- 14.6 mmHg, but there were no
      significant changes in bcmicropO, abSsO2 or flSsO2. Following reinfusion all
      parameters returned to values that were not statistically different from their
      pre-haemorrhage values. The dynamic recordings of all the oxygenation parameters
      indicated that they were sensitive indicators of the degree of haemorrhage during
      the experiments.

PMID- 23852475
TI  - Heart rate variability in newborns with hypoxic brain injury.
AB  - In neonatal intensive care units, there is a need for continuous monitoring of
      sick newborns with perinatal hypoxic ischemic brain injury (HIE). We assessed the
      utility of heart rate variability (HRV) in newborns with acute HIE undergoing
      simultaneous continuous EEG (cEEG) and ECG monitoring. HIE was classified using
      clinical criteria as well as visual grading of cEEG. Newborns were divided into
      two groups depending on the severity of the hypoxic injury and outcome. Various
      HRV parameters were compared between these groups, and significantly decreased
      HRV was found in neonates with severe HIE. As HRV is affected by many factors, it
      is difficult to attribute this difference solely to HIE. However, this study
      suggests that further investigation of HRV as a monitoring tool for acute
      neonatal hypoxic injury is warranted. 

PMID- 23852477
TI  - Hemispheric differences of motor execution: a near-infrared spectroscopy study.
AB  - Distal movements of the limbs are predominantly controlled by the contralateral
      hemisphere. However, functional neuroimaging studies do not unequivocally
      demonstrate a lateralization of the cerebral activation during hand movements.
      While some studies show a predominant activation of the contralateral hemisphere,
      other studies provide evidence for a symmetrically distributed bihemispheric
      activation. However, the divergent results may also be due to methodological
      shortcomings. Therefore, the present study using functional near-infrared
      spectroscopy examines cerebral activation in both hemispheres during motor
      actions of the right and left hands. Twenty participants performed a
      flexion/extension task with the right- or left-hand thumb. Cerebral oxygenation
      changes were recorded from 48 channels over the primary motor, pre-motor,
      supplementary motor, primary somatosensory cortex, subcentral area, and the
      supramarginal gyrus of each hemisphere. A consistent increase of cerebral
      oxygenation was found for oxygenated and for total hemoglobin in the hemisphere
      contralateral to the moving hand, regardless of the laterality. These findings
      are in line with previous data from localization [1-3] and brain imaging studies
      [4-6]. The present data support the proposition that there is no hemispheric
      specialization for simple distal motor tasks. Both hemispheres are equally
      activated during movement of the contralateral upper limb. 

PMID- 23852478
TI  - Acute stress exposure preceding global brain ischemia accelerates decreased
      doublecortin expression in the rat retrosplenial cortex.
AB  - BACKGROUND: Psychological distress is a risk factor of stroke in humans and
      worsens the behavioral and neurological outcomes. In rats, acute stress exposure
      preceding ischemic events attenuates learning and memory. The retrosplenial
      cortex (RS) plays an important role in these functions, and global brain ischemia
      (GBI) or acute stress exposure can induce a decrease in expression of the
      immature neuronal marker, doublecortin (DCX), in the RS. However, little is known
      about the DCX expression in the RS after stress exposure prior to GBI. METHODS:
      Eighteen male Sprague-Dawley rats were used. Acute stress exposure was applied as
      the forced swim paradigm and GBI was induced by bilateral common carotid arterial
      occlusion for 10 min. The rats were divided into three groups: GBI model
      preconditioned by stress (n = 6, Group P), GBI model preconditioned by non-stress
      (n = 6, Group G), and controls (n = 6, Group C). We performed
      immunohistochemistry to observe and analyze the DCX-expressing cells and Fluoro
      Jade B (FJB) staining to detect cell death in the RS after GBI in each group.
      RESULTS: The total number of DCX-expressing cells was 1,032, 1,219, and 1,904 in
      Group P, Group G, and Group C, respectively. The mean number of DCX-expressing
      cells per unit area was significantly lower in Group P and Group G than in Group
      C (P < 0.001). Moreover, the number was significantly lower in Group P than in
      Group G (P < 0.05). In each group, no FJB positive cells were observed.
      CONCLUSION: DCX plays an important role in various cytoskeletal changes.
      Preconditioning by acute stress exposure accelerated the decrease in DCX
      expression in the RS after GBI.

PMID- 23852479
TI  - Effects of transcranial direct current stimulation of the motor cortex on
      prefrontal cortex activation during a neuromuscular fatigue task: an fNIRS study.
AB  - This study investigated whether manipulation of motor cortex excitability by
      transcranial direct current stimulation (tDCS) modulates neuromuscular fatigue
      and functional near-infrared spectroscopy (fNIRS)-derived prefrontal cortex (PFC)
      activation. Fifteen healthy men (27.7 +/- 8.4 years) underwent anodal (2 mA, 10
      min) and sham (2 mA, first 30 s only) tDCS delivered to the scalp over the right
      motor cortex. Subjects initially performed a baseline sustained submaximal (30 %
      maximal voluntary isometric contraction, MVC) isometric contraction task (SSIT)
      of the left elbow flexors until task failure, which was followed 50 min later by
      either an anodal or sham treatment condition, then a subsequent posttreatment
      SSIT. Endurance time (ET), torque integral (TI), and fNIRS-derived contralateral
      PFC oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentration changes
      were determined at task failure. Results indicated that during the baseline and
      posttreatment SSIT, there were no significant differences in TI and ET, and
      increases in fNIRS-derived PFC activation at task failure were observed similarly
      regardless of the tDCS conditions. This suggests that the PFC neuronal activation
      to maintain muscle force production was not modulated by anodal tDCS. 

PMID- 23852480
TI  - The effect of inner speech on arterial CO2 and cerebral hemodynamics and
      oxygenation: a functional NIRS study.
AB  - The aim of the present study was (i) to investigate the effect of inner speech on
      cerebral hemodynamics and oxygenation, and (ii) to analyze if these changes could
      be the result of alternations of the arterial carbon dioxide pressure (PaCO2). To
      this end, in seven adult volunteers, we measured changes of cerebral absolute
      [O2Hb], [HHb], [tHb] concentrations and tissue oxygen saturation (StO2) (over the
      left and right anterior prefrontal cortex (PFC)), as well as changes in end-tidal
      CO2 (PETCO2), a reliable and accurate estimate of PaCO2. Each subject performed
      three different tasks (inner recitation of hexameter (IRH) or prose (IRP) verses)
      and a control task (mental arithmetic (MA)) on different days according to a
      randomized crossover design. Statistical analysis was applied to the differences
      between pre-baseline, two tasks, and four post-baseline periods. The two brain
      hemispheres and three tasks were tested separately. During the tasks, we found
      (i) PETCO2 decreased significantly (p < 0.05) during the IRH ( ~ 3 mmHg) and MA (
      ~ 0.5 mmHg) task. (ii) [O2Hb] and StO2 decreased significantly during IRH ( ~ 1.5
      MUM; ~ 2 %), IRP ( ~ 1 MUM; ~ 1.5 %), and MA ( ~ 1 MUM; ~ 1.5 %) tasks. During
      the post-baseline period, [O2Hb] and [tHb] of the left PFC decreased
      significantly after the IRP and MA task ( ~ 1 MUM and ~ 2 MUM, respectively). In
      conclusion, the study showed that inner speech affects PaCO2, probably due to
      changes in respiration. Although a decrease in PaCO2 is causing cerebral
      vasoconstriction and could potentially explain the decreases of [O2Hb] and StO2
      during inner speech, the changes in PaCO2 were significantly different between
      the three tasks (no change in PaCO2 for MA) but led to very similar changes in
      [O2Hb] and StO2. Thus, the cerebral changes cannot solely be explained by PaCO2. 

PMID- 23852481
TI  - Investigation of frontal lobe activation with fNIRS and systemic changes during
      video gaming.
AB  - Frontal lobe activation caused by tasks such as videogames can be investigated
      using multichannel near-infrared spectroscopy (fNIRS), sometimes called optical
      topography. The aims of this study are to investigate the effects of video gaming
      (fighting and puzzle games) in the brain and the systemic physiology and to
      determine whether systemic responses during the gaming task are associated with
      the measurement of localised cerebral haemodynamic changes as measured by fNIRS.
      We used a continuous-wave 8-channel fNIRS system to measure the changes in
      concentration of oxy-haemoglobin (HbO2) and deoxy-haemoglobin (HHb) and changes
      in total haemoglobin (DeltatHb = DeltaHbO2 + DeltaHHb) over the frontal lobe in
      30 healthy volunteers. The Portapres system was used to measure mean blood
      pressure (MBP) and heart rate (HR), and a laser Doppler was employed to measure
      the changes in scalp blood flow (or flux). Even though we observed significant
      changes in systemic variables during gaming, in particular in scalp flow, we also
      managed to see localised activation patterns over the frontal polar (FP1) region.
      However, in some channels over the frontal lobe, we also observed significant
      correlations between the HbO2 and systemic variables. 

PMID- 23852482
TI  - Effect of valsalva maneuver-induced hemodynamic changes on brain near-infrared
      spectroscopy measurements.
AB  - Near-infrared spectroscopy (NIRS) is widely used to measure human brain
      activation on the basis of cerebral hemodynamic response. However, a limitation
      of NIRS is that systemic changes influence the measured signals. The purpose of
      this study was to clarify the relationship between NIRS signals and blood
      pressure during the Valsalva maneuver. Nine healthy volunteers performed a 20-s
      Valsalva maneuver to change their blood pressure. Changes in oxyhemoglobin (O2Hb)
      concentration were measured with 34 channels with an inter-optode distance of 30
      mm for deep-penetration measurements (deepO2Hb) and 9 channels with an inter
      optode distance of 15 mm for shallow-penetration measurements (shallowO2Hb). The
      difference value (diffO2Hb) between deepO2Hb and shallowO2Hb was calculated. Mean
      arterial pressure (MAP) was recorded by volume clamping the finger pulse, and
      skin blood flow changes were measured at the forehead. Pearson's correlation
      coefficients between deepO2Hb and MAP, shallowO2Hb and MAP, and diffO2Hb and MAP
      were 0.893 (P < 0.01), 0.963 (P < 0.01), and 0.831 (P < 0.01), respectively. The
      results suggest that regional and systemic changes in the cardiovascular state
      strongly influence NIRS signals. 

PMID- 23852483
TI  - Effect of maternal use of labetalol on the cerebral autoregulation in premature
      infants.
AB  - Hypertensive disorders of pregnancy (HDP) are normally treated to avoid maternal
      complications. In this study we aimed to investigate if there was an effect of
      maternal HDP treatment on the cerebral autoregulation of the neonates by
      analysing measurements of mean arterial blood pressure (MABP) and rScO2 by means
      of correlation, coherence, and transfer function analysis. We found that these
      infants presented higher values of transfer function gain, which indicates
      impaired cerebral autoregulation, with a decreasing trend towards normality. We
      hypothesised that this trend was due to a vasodilation effect of the maternal use
      of labetalol due to accumulation, which disappeared by the third day after birth.
      Therefore, we investigated the values of pulse pressure in order to find evidence
      for a vasodilatory effect. We found that lower values of pulse pressure were
      present in these infants when compared with a control population, which, together
      with increased transfer function gain values, suggests an effect of the drug on
      the cerebral autoregulation. 

PMID- 23852484
TI  - Brain tissue oxygen saturation increases during the night in adolescents.
AB  - How does the oxygen metabolism change during sleep? We aimed to measure the
      change in brain tissue oxygen saturation (StO2) before and after sleep with near
      infrared spectroscopy (NIRS) using an in-house developed sensor. According to the
      synaptic homeostasis hypothesis [1], synaptic downscaling during sleep would
      result in reduced energy consumption. Thus, this reduced energy demands should be
      reflected in the oxygen metabolism and StO2. Thirteen nights of 7 male subjects
      (age 11-16 years, one subject contributed only one night, all others two) were
      included in the analysis. We performed NIRS measurements throughout the entire
      night. The NIRS sensor was placed close to electrode position Fp1 (international
      10/20 system), over the left frontal cortex. Absolute StO2 and total haemoglobin
      (tHb) were calculated from the NIRS measurements using a self-calibrating method
      [2]. StO2 and tHb during the awake period prior to sleep and after awakening were
      compared. The subjects were instructed to lie in bed in the same position before
      and after sleep. Values of the two nights were averaged for each subject.
      Furthermore, a linear regression line was fit through the all-night StO2
      recordings. We found an increase in StO2 by 4.32 +/- 1.76 % (mean +/- SD, paired
      t-test p < 0.001, n = 7) in the morning compared to evening, while tHb did not
      change (1.02 +/- 6.81 MUM p = 0.704, n = 7). Since the tHb remained at a similar
      level after sleep, this increase in StO2 indicates that in the morning more
      oxygenated blood and less deoxygenated blood was present in the brain compared to
      the evening. The slope of the regression line was 0.37 +/- 0.13 % h(-1) leading
      to a similar increase of StO2 in the course of sleep. This may be interpreted as
      a reduced oxygen consumption or energy metabolism after sleep. 

PMID- 23852485
TI  - Changes of cerebral oxygen metabolism and hemodynamics during ECPR with
      hypothermia measured by near-infrared spectroscopy: a pilot study.
AB  - BACKGROUND: The 2010 CPR Guidelines recommend that extracorporeal cardiopulmonary
      resuscitation (ECPR) using an emergency cardiopulmonary bypass (CPB) should be
      considered for patients with cardiac arrest. However, it is not yet clear whether
      this therapy can improve cerebral circulation and oxygenation in these patients.
      To clarify this issue, we evaluated changes of cerebral blood oxygenation (CBO)
      during ECPR using near-infrared spectroscopy (NIRS). METHODS: We employed NIRS to
      measure CBO in the bilateral frontal lobe in patients transported to the
      emergency room (ER) after out-of-hospital cardiac arrest between November 2009
      and June 2011. RESULTS: Fifteen patients met the above criteria. The tissue
      oxygenation index (TOI) on arrival at the ER was 36.5 %. This increased to 67.8 %
      during ECPR (P < 0.001). The one patient whose TOI subsequently decreased had a
      favorable neurological outcome. CONCLUSION: Increase of TOI during ECPR might
      reflect an improvement in cerebral blood flow, while decrease of TOI after ECPR
      might reflect oxygen utilization by the brain tissue as a result of neuronal cell
      survival. NIRS may be useful for monitoring cerebral hemodynamics and oxygen
      metabolism during CPR.

PMID- 23852486
TI  - Analysis of NIRS-based muscle oxygenation parameters by inclusion of adipose
      tissue thickness.
AB  - The assessment of muscle oxygenation by non-invasive near-infrared spectroscopy
      generally assumes a homogeneous medium, and this is flawed for large adipose
      tissue layers underneath the skin. Here we summarize the influence of the adipose
      tissue thickness on the oxygenation data, show that the adipose layer can be
      measured by NIRS and indicate a possible correction algorithm. Spectroscopic
      evidence suggests the usefulness of this algorithm, however, not in all subjects.

PMID- 23852487
TI  - Statistical treatment of oxygenation-related data in muscle tissue.
AB  - Muscle oxygenation is determined not only by the flow and oxygen content of the
      supplying blood but also by the density of the capillary network, the
      heterogeneity of the distribution of the capillaries and the properties and
      distribution of the muscle fibres. The distribution of the capillaries is
      adequately analysed by the method of capillary domains, which also allows to link
      capillaries to individual fibres. Thus, capillarisation can be linked to cell
      properties like fibre cross-sectional surface area and perimeter, and oxygen
      consumption of the individual muscle fibres. However, in order to meaningfully
      characterise tissue properties, such linkage has to be done for groups of cells.
      Since most of the data are not normally distributed - domains are lognormally
      distributed, but how fibre cross-sectional areas are distributed is unknown - a
      dedicated statistical analysis is required, particularly since none of the
      variables is independent. 

PMID- 23852488
TI  - O2 saturation in the intercostal space during moderate and heavy constant-load
      exercise.
AB  - To examine the hypothesis that the relationship between minute ventilation (VE)
      and deoxygenation from the intercostal space (IC) would be steady regardless of
      exercise protocols, if an increase in O2 consumption of the accessory respiratory
      muscles with an increase of VE brings about deoxygenation in IC, we measured the
      relationship between VE and O2 saturation in IC (SO2IC) during a constant-load
      exercise test (CET), and the relationship was compared with that during a ramp
      incremental exercise test (RIET). Six male subjects performed RIET. On a
      different day, the subjects performed a moderate and heavy CET (CET_MOD and
      CET_HVY, respectively). SO2IC decreased from the start of both CET_MOD and
      CET_HVY and changed little from 2 min. Moreover, SO2IC was significantly lower
      during CET_HVY than during CET_MOD. In comparison between RIET and CET_HVY at the
      similar VE level, SO2IC was significantly higher during CET_HVY than RIET. These
      results suggest that the decrease in SO2IC was caused not only by an increase in
      O2 consumption in IC with an increase in VE but also by a decrease in O2 supply. 

PMID- 23852489
TI  - Muscle, prefrontal, and motor cortex oxygenation profiles during prolonged
      fatiguing exercise.
AB  - This study aimed to compare changes in skeletal muscle, prefrontal (PFC), and
      motor (MC) cortex hemodynamics during prolonged (i.e., 4-h) fatiguing whole-body
      exercise using multichannel near-infrared spectroscopy (NIRS). Ten subjects
      completed three successive 80-min cycling bouts at 45 % of their maximal power
      output. After the 4-h cycling, maximal voluntary contraction force of the leg was
      decreased by ~25 %. Muscle exhibited reproductive deoxygenation patterns during
      each of the three bouts, whereas intra-bout cerebral hemodynamics were different
      throughout the protocol. Results demonstrate that specific responses to fatiguing
      exercise are found between tissues but also between cortical sites involved in
      cycling, as shown by concomitant PFC hyperoxygenation and MC deoxygenation in the
      first 80 min of exercise. Further insights are needed to understand the
      consequences of these changes regarding the integrative control of motor output
      while fatigue develops over several hours. 

PMID- 23852490
TI  - Aging affects spatial distribution of leg muscle oxygen saturation during ramp
      cycling exercise.
AB  - We compared muscle oxygen saturation (SmO2) responses in several leg muscles and
      within a single muscle during ramp cycling exercise between elderly men (n = 8;
      age, 65 +/- 3 years; ELD) and young men (n = 10; age, 23 +/- 3 years; YNG). SmO2
      was monitored at the distal site of the vastus lateralis (VLd), proximal site of
      the vastus lateralis (VLp), rectus femoris (RF), vastus medialis (VM), biceps
      femoris (BF), gastrocnemius lateralis (GL), gastrocnemius medialis (GM), and
      tibialis anterior (TA) by near-infrared spatial resolved spectroscopy. During
      submaximal exercise, significantly lower SmO2 at a given absolute work rate was
      observed in VLd, RF, BF, GL, and TA but not in VLp, VM, and GM in ELD than in
      YNG. In contrast, at all measurement sites, SmO2 at peak exercise was not
      significantly different between groups. These results indicate that the effects
      of aging on SmO2 responses are heterogeneous between leg muscles and also within
      a single muscle. The lower SmO2 in older men may have been caused by reduced
      muscle blood flow or altered blood flow distribution. 

PMID- 23852491
TI  - Which is the best indicator of muscle oxygen extraction during exercise using
      NIRS?: Evidence that HHb is not the candidate.
AB  - Recently, deoxygenated hemoglobin (HHb) has been used as one of the most popular
      indicators of muscle O2 extraction during exercise in the field of exercise
      physiology. However, HHb may not sufficiently represent muscle O2 extraction, as
      total hemoglobin (tHb) is not stable during exercise. The purpose of this study
      was to measure various muscle oxygenation signals during cycle exercise and
      clarify which is the best indicator of muscle O2 extraction during exercise using
      NIRS. Ten healthy men performed 6-min cycle exercise at both moderate and heavy
      work rates. Oxygenated hemoglobin (O2-Hb), HHb, tHb, and muscle tissue oxygen
      saturation (SmO2) were measured with near-infrared spatial resolved spectroscopy
      from the vastus lateralis muscle. Skin blood flow (sBF) was also monitored at a
      site close to the NIRS probe. During moderate exercise, tHb, O2-Hb, and SmO2
      displayed progressive increases until the end of exercise. In contrast, HHb
      remained stable during moderate work rate. sBF remained stable during moderate
      exercise but showed a progressive decrease at heavy work rate. These results
      provide evidence that HHb may not sufficiently represent muscle O2 extraction
      since tHb is not stable during exercise and HHb is insensitive to exercise
      induced hyperaemia. 

PMID- 23852492
TI  - Tissue oxygenation during exercise measured with NIRS: reproducibility and
      influence of wavelengths.
AB  - Near-infrared spectroscopy (NIRS) is widely used for the measurement of skeletal
      muscle oxygenation during exercise as it reflects muscle metabolism, and most
      studies report a large variability between subjects. Here we assess the data
      quality of tissue oxygen saturation (SO2) and oxygenated (oxyHb) and deoxygenated
      (deoxyHb) haemoglobin concentrations recorded during an incremental cycling
      protocol in nine healthy volunteers. The protocol was repeated three times on the
      same day and a fourth session on a different day to estimate the reproducibility
      of the method with a broadband, spatially resolved spectroscopy (SRS) system. We
      found that the inter-subject variation in SO2 (standard deviation ~ 6 %) was
      considerably larger than the reproducibility (~ 1.5 %) both for the same-day and
      different-day tests. The reproducibility of changes in SO2 was better than 1 %. 

PMID- 23852493
TI  - Using portable NIRS to compare arm and leg muscle oxygenation during roller
      skiing in biathletes: a case study.
AB  - Portable near-infrared spectroscopy (NIRS) has been shown to be a useful and
      reliable tool for monitoring muscle oxygenation and blood volume changes during
      dynamic exercise in elite athletes. The wearable nature of such technology
      permits the measurement of specific muscles/muscle groups during realistic sport
      specific exercise tasks in an outdoor environment. The aim of this case study was
      to observe the effect on arm and leg muscle oxygenation of roller skiing over a
      typical outdoor racing course. Such information is required by coaches in order
      to ascertain whether an athlete is using the correct technique at different
      stages of the course. Two wearable NIRS devices (PortaMon, Artinis Medical
      Systems) were used to compare muscle tissue oxygen saturation (TSI%) and total
      haemoglobin (tHb) changes in the quadriceps muscle group (vastus lateralis) and a
      muscle of the upper arm (triceps) during roller skiing. During the flat section,
      quadriceps DeltaTSI remained steady in both subjects, whereas triceps DeltaTSI
      showed a reduction (-10 %). During the steep uphill section of the course, arm
      and leg TSI decreased equally in one subject (DeltaTSI = -10 %), whereas there
      was a difference between the two muscle groups in the other subject
      (DeltaTSIquadriceps = -2 %; DeltaTSItriceps = -7 %). A difference was also seen
      between subjects during the downhill section of the course. This study presents
      the first example of the use of portable NIRS to assess oxygenation and blood
      volume changes in multiple muscle groups during roller skiing in a realistic,
      outdoor setting. 

PMID- 23852494
TI  - The use of portable NIRS to measure muscle oxygenation and haemodynamics during a
      repeated sprint running test.
AB  - Portable near-infrared spectroscopy (NIRS) devices were originally developed for
      use in exercise and sports science by Britton Chance in the 1990s (the RunMan and
      microRunman series). However, only recently with the development of more robust,
      and wireless systems, has the routine use in elite sport become possible. As with
      the medical use of NIRS, finding applications of the technology that are relevant
      to practitioners is the key issue. One option is to use NIRS to track exercise
      training-induced adaptations in muscle. Portable NIRS devices enable monitoring
      during the normal 'field' routine uses to assess fitness, such as repeat sprint
      shuttle tests. Knowledge about the acute physiological responses to these
      specific tests has practical applications within team sport training
      prescription, where development of both central and peripheral determinants of
      high-intensity intermittent exercise needs to be considered. The purpose of this
      study was to observe NIRS-detected parameters during a repeat sprint test. We
      used the PortaMon, a two wavelength spatially resolved NIR spectrometer
      manufactured by Artinis Inc., to assess NIR changes in the gastrocnemius muscle
      of both the left and right leg during high-intensity running. Six university
      standard rugby players were assessed (age 20 +/- 1.5 years; height 183 +/- 1.0
      cm; weight 89.4 +/- 5.8 kg; body fat 12.2 +/- 3.0 %); the subjects completed nine
      repeated shuttle runs, which incorporated forward, backward and change of
      direction movements. Individual sprint time, total time to complete test, blood
      lactate response (BL), heart rate values (HR) and haemoglobin variables
      (DeltaHHb, DeltatHb, DeltaHbO2 and DeltaTSI%) were measured. Total time to
      complete the test was 260 +/- 20 s, final blood lactate was 14.3 +/- 2.8 mM, and
      maximal HR 182 +/- 5 bpm. NIRS variables displayed no differences between right
      and left legs. During the test, the group-averaged data showed a clear decrease
      in HbO2 (max. decrease 11.41 +/- 4.95 MUM), increase in HHb (max. increase 17.65
      +/- 4.48 MUM) and drop in %TSI (max. drop - 24.44 +/- 4.63 %). tHb was largely
      unchanged. However, large interindividual differences were seen for all the NIRS
      parameters. In conclusion, this observational study suggests that a portable NIRS
      device is both robust and sensitive enough to detect haemoglobin changes during a
      high-intensity repeated shuttle run test. It therefore has the possibility to be
      used to assess exercise training-induced adaptations following a specific
      training protocol. However, it is at present unclear, given the individual
      variability, whether NIRS can be used to assess individual performance. We
      recommend that future studies report individual as well as group data. 

PMID- 23852495
TI  - Amifostine acts upon mitochondria to stimulate growth of bone marrow and regulate
      cytokines.
AB  - Amifostine is a first-line cytoprotective drug used to prevent radiotherapy
      induced or chemotherapy-induced injuries. However, its mechanism of action is not
      well understood. In this study, freshly harvested bone marrow cells were treated
      with amifostine and analyzed with a series of mitochondrial indices. In vitro
      results showed that bone marrow cells treated with amifostine 0.5 h before
      irradiation (0.5 Gy) experienced several benefits, as compared to vehicle
      controls, including (1) reduced reactive oxygen species levels, which reduced the
      production of free radicals; (2) better preservation of mitochondria, as
      indicated by MitoTracker-positive staining and the increased intensity of
      staining; (3) reduced apoptosis, as demonstrated by Annexin V staining; and (4) a
      better proliferation rate, as illustrated by MTT assay. Our in vitro studies
      showed that amifostine-treated mice exhibited (1) higher ATP production; (2)
      reduced plasma IL-2 levels, suppressing the immune response triggered by
      radiotoxicity; and (3) enhanced radiation-induced production of granulocyte
      colony-stimulating factor. All of these processes benefit recovery from radiation
      induced damage. 

PMID- 23852496
TI  - Hypoxia, lactate accumulation, and acidosis: siblings or accomplices driving
      tumor progression and resistance to therapy?
AB  - This chapter briefly summarizes the most important processes by which hypoxia,
      lactate accumulation, and acidosis may influence malignant progression and
      therapeutic resistance of solid malignant tumors. While these phenomena are often
      elements of an integrated reaction, they may occur independently of each other
      under certain circumstances. The latter information may be of interest with
      regard to possible "targeted" therapeutic interventions. 

PMID- 23852497
TI  - Breast cancer detection of large size to DCIS by hypoxia and angiogenesis using
      NIRS.
AB  - This investigation aimed to test all tumor-bearing patients who undergo biopsy to
      see if angiogenesis and hypoxia can detect cancer. We used continuous-wave near
      infrared spectroscopy (NIRS) to measure blood hemoglobin concentration to obtain
      blood volume or total hemoglobin [Hbtot] and oxygen saturation for the
      angiogenesis and hypoxic biomarkers. The contralateral breast was used as a
      reference to derive the difference from breast tumor as a difference in total
      hemoglobin Delta[HBtot] and a difference in deoxygenation Delta([Hb]-[HbO2]). A
      total of 91 invasive cancers, 26 DCIS, 45 fibroblastomas, 96 benign tumors
      excluding cysts, and 67 normal breasts were examined from four hospitals. In
      larger-size tumors, there is significantly higher deoxygenation in invasive and
      ductal carcinoma in situ (DCIS) than in that of benign tumors, but no significant
      difference was seen in smaller tumors of <= 1 cm. With the two parameters of high
      total hemoglobin and hypoxia score, the sensitivity and specificity of cancer
      detection were 60.3 % and 85.3 %, respectively. In summary, smaller-size tumors
      are difficult to detect with NIRS, whereas DCIS can be detected by the same total
      hemoglobin and hypoxic score in our study.

PMID- 23852498
TI  - Impact of extracellular acidosis on intracellular pH control and cell signaling
      in tumor cells.
AB  - Cells in solid tumors generate an extracellular acidosis due to the Warburg
      effect and tissue hypoxia. Acidosis can affect the functional behavior of tumor
      cells, causing, e.g., multidrug resistance. In this process ERK1/2 and p38
      mitogen-activated protein kinases (MAPK) seem to play a key role. However, the
      underlying mechanism of MAPK activation by extracellular acidosis remains
      unclear. Experiments were performed in three tumor and three normal tissue cell
      lines in which the cells were exposed to an extracellular pH of 6.6 for 3 h.
      Intracellular pH (pHi), protein expression and activation, acidosis-induced
      transactivation, and reactive oxygen species (ROS) formation were measured.
      Extracellular acidosis resulted in a rapid and sustained decrease of pHi leading
      to a reversal of the extra-/intracellular pH gradient. Extracellular acidosis led
      to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in three
      of six cell lines. Furthermore, p38 phosphorylation was also observed during sole
      intracellular lactacidosis at normal pHe. Acidosis-enhanced formation of ROS,
      probably originating from mitochondria, seems to trigger MAPK phosphorylation.
      Finally, acidosis increased phosphorylation of the transcription factor CREB and
      resulted in increased transcriptional activity. Thus, an acidic tumor
      microenvironment can induce a longer-lasting p38 CREB-mediated change in the
      transcriptional program. 

PMID- 23852499
TI  - Tumor oxygenation: an appraisal of past and present concepts and a look into the
      future : Arisztid G. B. Kovach Lecture.
AB  - Since 1970, the multifactorial pathogenesis of the deficient and heterogeneous
      oxygenation of transplanted murine tumors and of human cancers (including
      parameters determining oxygen delivery, e.g., blood flow, diffusion geometry,
      oxygen transport capacity of the blood) has been investigated in vivo. Hypoxia
      and/or anoxia was quantitatively assessed and characterized using microtechniques
      and special preclinical tumor models. Hypoxia subtypes were identified, and
      critical supply conditions were theoretically analyzed. In the 1980s, first
      experiments on humans were carried out in cancers of the rectum and of the oral
      cavity. In the 1990s, the clinical investigations were carried out on cancers of
      the breast and of the uterine cervix, clearly showing that hypoxia is a hallmark
      of locally advanced human tumors. In multivariate analysis, hypoxia was found to
      be an independent, adverse prognostic factor for patient survival due to hypoxia
      driven malignant progression and hypoxia-associated resistance to anticancer
      therapy. 

PMID- 23852500
TI  - In vivo metabolic evaluation of breast tumor mouse xenografts for predicting
      aggressiveness using the hyperpolarized (13)C-NMR technique.
AB  - In vivo imaging/spectroscopic biomarkers for solid tumor aggressiveness are
      needed in the clinic to facilitate cancer diagnosis and treatment strategies. In
      mouse models of human melanoma and breast cancer, we were able to detect the
      metabolic differences among tumors of different metastatic potential and between
      normal and cancer tissues by optical imaging of the mitochondrial redox state of
      snap-frozen tissue samples. Such metabolic differences indicate that tumors of
      different aggressiveness have different metabolic homeostasis, which supports
      that kinetic parameters such as rate constant(s) can also serve as biomarkers for
      cancer aggressiveness and treatment response. Here we present our preliminary
      study on the mouse xenografts of the aggressive and indolent human breast cancer
      cell lines using the hyperpolarized (13)C-NMR (HP-NMR) technique. By recording
      the time courses of (13)C-pyruvate tracer and its metabolite signals in vivo,
      particularly the (13)C-lactate signal, the apparent rate constants of both the
      forward and reverse reactions catalyzed by lactate dehydrogenase (LDH) were
      extracted via the ratiometric modeling of the two-site exchange reaction that we
      developed. Data from four breast tumors (MCF-7, MDA-MB-468, and MDA-MB-231 medium
      and large) with different aggressiveness are included. We demonstrate the
      feasibility to quantify the apparent rate constants of LDH reactions in breast
      tumor xenografts. 

PMID- 23852501
TI  - Mapping the redox state of CHOP-treated non-Hodgkin's lymphoma xenografts in
      mice.
AB  - Drug treatment may alter the metabolism of cancer cells and may alter the
      mitochondrial redox state. Using the redox scanner that collects the fluorescence
      signals from both the oxidized flavoproteins (Fp) and the reduced form of
      nicotinamide adenine dinucleotide (NADH) in snap-frozen tumor tissues, we
      investigated the effects of chemotherapy on mouse xenografts of a human diffuse
      large B-cell lymphoma cell line (DLCL2). The mice in the treatment group were
      treated with CHOP - cyclophosphamide (C) + hydroxydoxorubicin (H) + Oncovin (O) +
      prednisone (P) using the following regimen: CHO administration on day 1 followed
      by prednisone administration on day 1-5. On day 5 the mitochondrial redox state
      of the treated group was slightly more reduced than that of the control group (p
      = 0.049), and the Fp content of the treated group was significantly decreased (p
      = 0.033). 

PMID- 23852502
TI  - Maternal bias in mouse radiosensitivity: the role of the mitochondrial PTP.
AB  - This study investigated, at the molecular level, mitochondrial responses to
      radiation. In three mouse strains, we found the following: (1) mitochondrial
      response to calcium stress was associated with a strain's susceptibility to gamma
      radiation; (2) gamma-radiation increased this calcium stress response in a dose
      responsive manner; (3) the mitochondrial DNA (mtDNA) copy number in the liver of
      the radiosensitive mouse strain was significantly lower, as compared to that of
      the radioresistant strain; (4) adenine nucleotide translocase (ANT) mRNA copy
      numbers were significantly lower in the radiosensitive strain; (5) the F1
      offspring (BC/C57M) of radiosensitive females mated with radioresistant males
      exhibited a significant difference in calcium stress response from that of the
      radiation-resistant strain, but the reverse cross did not exhibit this
      difference; and (6) only those mitochondria extracted from the livers of
      irradiated BC/C57M mice exhibited a heightened calcium stress response. We
      propose that a genetic change in ANT and a postirradiation change involving
      either mtDNA-encoded protein replacement or altered mtDNA association fit these
      data. 

PMID- 23852503
TI  - Interleukin 11 protects bone marrow mitochondria from radiation damage.
AB  - Interleukin 11 (IL-11) is a multifunctional cytokine isolated from bone marrow
      (BM)-derived stromal cells that promotes hematopoiesis and prolongs the life span
      of lethally irradiated animals. However, the underlying mechanism for the
      protective effect of IL-11 on BM is unclear. In this study, we explored the
      effect of IL-11 on irradiated BM cells. Freshly harvested BM cells were
      pretreated with 20 ng/ml of recombinant IL-11 for 30 min, irradiated with a dose
      of 0.5 Gy, cultured for 24 h, and then subjected to several assays. In vitro data
      showed that, as compared to the vehicle controls, IL-11: (1) reduced the
      production of reactive oxygen species; (2) reduced the alteration of
      mitochondrial membrane potential; (3) increased MitoTracker staining, suggesting
      that the number of mitochondria and their functions were better maintained; and
      (4) reduced apoptosis of BM cells and enhanced BM cell proliferation. In vivo
      studies of mice pretreated with saline or 100 MUg/kg of IL-11 at 12 and 2 h
      before 10-Gy total body irradiation (TBI) demonstrated that G-CSF and IL-6 were
      significantly upregulated, whereas IL-2 and IL-4 were reduced. We found that IL
      11 protects mitochondrial functions, acts with G-CSF and IL-6 to stimulate the
      growth of radiation-damaged BM, and reduces the immune response to radiation
      injury. 

PMID- 23852504
TI  - Tumor reoxygenation following administration of the EGFR inhibitor, gefitinib, in
      experimental tumors.
AB  - It is well recognized that tumor hypoxia is a critical determinant for response
      to therapy. The effect of an EGFR inhibitor/gefitinib (Iressa(r)) on tumor
      oxygenation was monitored daily using in vivo EPR (electron paramagnetic
      resonance) oximetry on TLT and FSaII tumor models. An increase in pO2 was shown
      at a dose of 45 mg/kg i.p. (n = 4/group/tumor model). This allowed the
      identification of a window of reoxygenation in both tumor models (with a maximum
      between 15 and 20 mmHg after 2 days of treatment). The increase in tumor
      oxygenation was shown to be the result of a decrease in oxygen consumption. This
      is the first report on the effect of gefitinib on oxygen consumption by tumor
      cells and subsequent increase in tumor oxygenation in vivo. 

PMID- 23852505
TI  - Radiation affects the responsiveness of bone marrow to G-CSF.
AB  - In this study, we investigated the response of irradiated bone marrow cells to
      granulocyte colony-stimulating factor (G-CSF). Freshly harvested bone marrow
      cells were treated with either saline (vehicle control) or 20 ng/ml of G-CSF.
      Thereafter, cells were separated into nonirradiated (no-IR) and irradiated (IR,
      0.5 Gy) groups. IR cells exhibited a higher proliferation rate in response to G
      CSF, as compared to the no-IR cells. Reduced levels of reactive oxygen species
      indicated that G-CSF-treated IR cells produced fewer free radicals, as compared
      to the no-IR cells. The G-CSF-treated IR cells also had a lower apoptotic rate
      than their no-IR counterparts. Furthermore, G-CSF-treated IR cells exhibited less
      alteration of mitochondrial membrane potential, as compared to the no-IR cells.
      Finally, the mitochondrial number increased in the G-CSF-treated IR cells. The
      radiation-induced increase in plasma IL-6 in vivo could be enhanced by the
      administration of G-CSF. The data suggest that radiation potentiates the response
      of bone marrow cells to G-CSF treatment. 

PMID- 23852506
TI  - Application of MOBILE (mapping of oxygen by imaging lipids relaxation
      enhancement) to study variations in tumor oxygenation.
AB  - The aim of the study was to sensitively monitor changes in tumor oxygen using the
      MOBILE (mapping of oxygen by imaging lipids relaxation enhancement) technique.
      This method was applied in mammary tumor mouse models on an 11.7T Bruker MRI
      system. MOBILE was compared with functional imaging R2*, R1 of water and with pO2
      measurements (using EPR oximetry and O2-dependent fluorescence quenching
      measurements). MOBILE was shown to be capable to monitor changes in oxygenation
      in tumor tissues. 

PMID- 23852507
TI  - Primo vascular system and its potential role in cancer metastasis.
AB  - The primo vascular system (PVS) is a newly found organ, which is distributed
      throughout the entire body. The system is composed of nodes storing many small
      cells and thin vessels branching out from the nodes. Inside the vessel there are
      multiple subvessels. The PVS is found in and on most organs, including the brain,
      and interestingly inside some lymph and blood vessels. The PVS is normally
      difficult to visualize due to its semitransparent optical property and its small
      size, which may be the main reason why it was not discovered until recently. The
      diameter of primo vessels (PVs) is in the range of 20-50 MUm and the size of a
      primo node (PN), 100-1,000 MUm. The outermost layer of the PVS is more porous
      than that of blood or lymph capillary vessels, and the nuclei of the PVS
      endothelial cells are rod shaped. Important PVS properties reported are: in the
      fluid inside the PVS, there are cells presenting stem cell markers CD133, Oct4,
      and Nanog, which may imply that this system has a role in regeneration. Another
      very important finding is its potential relevance to cancer. According to results
      from an animal study using xenografts of various cancer types (lung, ovarian,
      skin, gastric cancer, and leukemia), as the tumor grows, the PVS is formed in a
      high density in the vicinity of the tumor. In addition, it was shown that PVs
      connect the primary and secondary tumors and that cancer cells were transported
      via the PVs in an active manner. In this report, we illustrated the formation of
      the PVS in breast cancer, and using the green fluorescent protein-expressing
      gastric cancer cell lines, we observed the cancer cell movement from the primary
      to the secondary sites during the cancer progression. 

PMID- 23852508
TI  - Pancreaticoduodenectomy using perioperative zymogen protein C to help prevent
      blood clotting: a trilogy on increased patient safety.
AB  - The blood clotting mechanism is a very important and complex physiologic process.
      Blood flow must be continuous through the blood vessels to provide essential
      oxygen and nutrients to the cells of the body. Dr. Melvin H. Knisely (Honorary
      First President of ISOTT, 1973) named and pioneered research in blood sludging
      and clotting which led to his nomination for the Nobel Prize by Dr. August Krogh
      in 1948. Abnormal clotting is a pathological state that can inhibit and prevent
      normal blood flow, leading to reduced oxygen transport to tissue from the
      microcirculation. It can result in the death of cells and tissues, including
      entire organs as well as the patient. Blood clotting and sludging are common
      occurrences during and after invasive surgery; thus, it is imperative to find
      safe procedures to reduce or prevent these deadly phenomena. All anticoagulants
      used today, for clot prevention and dissolution, can cause excessive bleeding
      that can lead to enormous medical expense to provide control, otherwise causing
      patient death. Protein C is a natural protein and is the pivotal anticoagulant in
      the blood. Due to the mechanism of converting the zymogen protein C (ZPC) to
      active protein C (APC), only when and where it is needed, and their respective
      half-lives in the body, the natural anticoagulant, antithrombotic characteristics
      of APC can be utilized without causing bleeds. 

PMID- 23852509
TI  - Inhibition of mammalian target of rapamycin induces renal mitochondrial
      uncoupling in rats.
AB  - The mechanisms underlying diabetic nephropathy are not fully understood. However,
      recent research indicates mitochondria dysfunction as a contributing factor.
      Mammalian target of rapamycin (mTOR) is a known regulator of mitochondria
      function and could therefore also be involved in the development of diabetic
      nephropathy. The present study investigates the role of mTOR for controlling the
      function of mitochondria isolated from normal and diabetic rat kidneys. Control
      and streptozotocin-induced diabetic rats were treated with the mTOR inhibitor
      rapamycin (0.2 mg/day) by oral gavage for 14 days, after which mitochondria
      function was investigated using high-resolution respirometry. Mitochondrial
      uncoupling was defined as increased oxygen usage unrelated to ATP production.
      mTOR inhibition induced mitochondria uncoupling in control rats, but did not
      affect the already occurring uncoupling in kidney mitochondria from diabetic
      animals. Inhibition of mTOR using rapamycin induces mitochondria uncoupling in
      control rats, suggesting a role of mTOR as a moderator of mitochondria
      efficiency. No effect of mTOR inhibition was observed in mitochondria from
      diabetic animals, suggesting that there are other pathways in addition to the
      mTOR pathway regulating mitochondria function in diabetes. The functional
      significance of the mTOR pathway in regulating mitochondria efficiency warrants
      further attention. 

PMID- 23852510
TI  - Molecular hydrogen consumption in the human body during the inhalation of
      hydrogen gas.
AB  - Inhaling or ingesting hydrogen (H2) gas improves oxidative stress-induced damage
      in animal models and humans. We previously reported that H2 was consumed
      throughout the human body after the ingestion of H2-rich water and that the H2
      consumption rate ([Formula: see text]) was 1.0 MUmol/min/m(2) body surface area.
      To confirm this result, we evaluated [Formula: see text]during the inhalation of
      low levels of H2 gas. After measuring the baseline levels of exhaled H2 during
      room air breathing via a one-way valve and a mouthpiece, the subject breathed low
      levels (160 ppm) of H2 gas mixed with purified artificial air. The H2 levels of
      their inspired and expired breath were measured by gas chromatography using a
      semiconductor sensor. [Formula: see text] was calculated using a ventilation
      equation derived from the inspired and expired concentrations of O2/CO2/H2, and
      the expired minute ventilation volume, which was measured with a respiromonitor.
      As a result, [Formula: see text] was found to be approximately 0.7
      MUmol/min/m(2)BSA, which was compatible with the findings we obtained using H2
      rich water. [Formula: see text] varied markedly when pretreatment fasting to
      reduce colonic fermentation was not employed, i.e., when the subject's baseline
      breath hydrogen level was 10 ppm or greater. Our H2 inhalation method might be
      useful for the noninvasive monitoring of hydroxyl radical production in the human
      body. 

PMID- 23852511
TI  - Oxidative metabolism: glucose versus ketones.
AB  - The coupling of upstream oxidative processes (glycolysis, beta-oxidation, CAC
      turnover) to mitochondrial oxidative phosphorylation (OXPHOS) under the driving
      conditions of energy demand by the cell results in the liberation of free energy
      as ATP. Perturbations in glycolytic CAC or OXPHOS can result in pathology or cell
      death. To better understand whole body energy expenditure during chronic ketosis,
      we used a diet-induced rat model of ketosis to determine if high-fat-carbohydrate
      restricted "ketogenic" diet results in changes in total energy expenditure (TEE).
      Consistent with previous reports of increased energy expenditure in mice, we
      hypothesized that rats fed ketogenic diet for 3 weeks would result in increased
      resting energy expenditure due to alterations in metabolism associated with a
      "switch" in energy substrate from glucose to ketone bodies. The rationale is
      ketone bodies are a more efficient fuel than glucose. Indirect calorimetric
      analysis revealed a moderate increase in VO2 and decreased VCO2 and heat with
      ketosis. These results suggest ketosis induces a moderate uncoupling state and
      less oxidative efficiency compared to glucose oxidation. 

PMID- 23852512
TI  - Modelling blood flow and metabolism in the piglet brain during hypoxia-ischaemia:
      simulating pH changes.
AB  - We describe the extension of a computational model of blood flow and metabolism
      in the piglet brain to investigate changes in neonatal intracellular brain pH
      during hypoxia-ischemia (HI). The model is able to simulate near-infrared
      spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS) measurements
      obtained from HI experiments conducted in piglets. We adopt a method of using
      (31)P-MRS data to estimate of intracellular pH and compare measured pH and
      oxygenation with their modelled counterparts. We show that both NIRS and MRS
      measurements are predicted well in the new version of the model. 

PMID- 23852513
TI  - Modelling blood flow and metabolism in the piglet brain during hypoxia-ischaemia:
      simulating brain energetics.
AB  - We have developed a computational model to simulate hypoxia-ischaemia (HI) in the
      neonatal piglet brain. It has been extended from a previous model by adding the
      simulation of carotid artery occlusion and including pH changes in the cytoplasm.
      Here, simulations from the model are compared with near-infrared spectroscopy
      (NIRS) and phosphorus magnetic resonance spectroscopy (MRS) measurements from two
      piglets during HI and short-term recovery. One of these piglets showed incomplete
      recovery after HI, and this is modelled by considering some of the cells to be
      dead. This is consistent with the results from MRS and the redox state of
      cytochrome-c-oxidase as measured by NIRS. However, the simulations do not match
      the NIRS haemoglobin measurements. The model therefore predicts that further
      physiological changes must also be taking place if the hypothesis of dead cells
      is correct. 

PMID- 23852514
TI  - Mathematical modelling of near-infrared spectroscopy signals and intracranial
      pressure in brain-injured patients.
AB  - Raised intracranial pressure (ICP) is a key concern following acute brain injury
      as it may be associated with cerebral hypoperfusion and poor outcome. In this
      research we describe a mathematical physiological model designed to interpret
      cerebral physiology from neuromonitoring: ICP, near-infrared spectroscopy and
      transcranial Doppler flow velocity. This aims to characterise the complex
      dynamics of cerebral compliance, cerebral blood volume, cerebral blood flow and
      their regulation in individual patients. Analysis of data from six brain-injured
      patients produces cohesive predictions of cerebral biomechanics suggesting
      reduced cerebral compliance, reduced volume compensation and impaired blood flow
      autoregulation. Patient-specific physiological modelling has the potential to
      predict the key biomechanical and haemodynamic changes following brain injury in
      individual patients, and might be used to inform individualised treatment
      strategies. 

PMID- 23852515
TI  - Dependence on NIRS source-detector spacing of cytochrome c oxidase response to
      hypoxia and hypercapnia in the adult brain.
AB  - Transcranial near-infrared spectroscopy (NIRS) provides an assessment of cerebral
      oxygen metabolism by monitoring concentration changes in oxidised cytochrome c
      oxidase Delta[oxCCO]. We investigated the response of Delta[oxCCO] to global
      changes in cerebral oxygen delivery at different source-detector separations in
      16 healthy adults. Hypoxaemia was induced by delivery of a hypoxic inspired gas
      mix and hypercapnia by addition of 6 % CO2 to the inspired gases. A hybrid
      optical spectrometer was used to measure frontal cortex light absorption and
      scattering at discrete wavelengths and broadband light attenuation at 20, 25, 30
      and 35 mm. Without optical scattering changes, a decrease in cerebral oxygen
      delivery, resulting from the reduction in arterial oxygen saturation during
      hypoxia, led to a decrease in Delta[oxCCO]. In contrast, Delta[oxCCO] increased
      when cerebral oxygen delivery increased due to increased cerebral blood flow
      during hypercapnia. In both cases the magnitude of the Delta[oxCCO] response
      increased from the detectors proximal (measuring superficial tissue layers) to
      the detectors distal (measuring deep tissue layers) to the broadband light
      source. We conclude that the Delta[oxCCO] response to hypoxia and hypercapnia
      appears to be dependent on penetration depth, possibly reflecting differences
      between the intra- and extracerebral tissue concentration of cytochrome c
      oxidase. 

PMID- 23852516
TI  - Modeling hemoglobin nitrite reductase activity as a mechanism of hypoxic
      vasodilation?
AB  - The brain's response to hypoxia is to increase cerebral blood flow (CBF).
      However, the molecular mechanism underpinning this phenomenon is controversial.
      We have developed a model to simulate brain blood flow and oxygen metabolism
      called BRAINSIGNALS. This model is primarily designed to assist in the
      interpretation of multimodal noninvasive clinical measurements. However, we have
      recently used this model to test the feasibility of a range of molecular
      mechanisms proposed to explain hypoxic vasodilation. An increase in the
      concentration of the vasodilator nitric oxide (NO) at low pO2 is a feature of
      many such mechanisms. One model suggests that mitochondrial cytochrome c oxidase
      (CCO) catalyzes the metabolism of NO. This metabolism declines at low pO2,
      resulting in an increase in the steady-state levels of NO and a consequent
      increase in CBF. Using BRAINSIGNALS we were able to model this effect. However,
      the increases in NO and CBF occurred at far lower pO2 values than predicted from
      physiological data (Rong et al. 2013 Adv Exp Med Biol. 765, 231-238). The aim of
      the present study was to test an alternative mechanism, one that actively
      generates NO as pO2 drops, namely, the reduction of nitrite to NO by
      deoxyhemoglobin. In this mechanism, NO synthesis has a maximum of NO production
      near the hemoglobin p50. The addition of this mechanism resulted in a
      significantly better fit to the experimental data of the CBF(PaO2) curve. 

PMID- 23852517
TI  - Development of a hybrid microwave-optical tissue oxygenation probe to measure
      thermal response in the deep tissue.
AB  - The design of a new non-invasive hybrid microwave-optical tissue oxygenation
      probe is presented, which consists of a microwave biocompatible antenna and an
      optical probe. The microwave antenna is capable of inducing localised heat in the
      deep tissue, causing tissue blood flow and therefore tissue oxygenation to
      change. These changes or thermal responses are measured by the optical probe
      using near-infrared spectroscopy. Thermal responses provide important information
      on thermoregulation in human tissue. The first prototype of the biocompatible
      antenna was developed and placed on the human calf for in vivo experiments. The
      measured results include oxy-, deoxy- and total haemoglobin concentration changes
      (DeltaHbO2/DeltaHHb/DeltaHbT), tissue oxygenation index and the normalised tissue
      haemoglobin index for two human subjects. Both DeltaHbO2 and DeltaHbT show an
      increase during 5 min of microwave exposure. The thermal response, defined as the
      ratio of the increase in DeltaHbT to the time duration, is 7.7 MUM/s for subject
      1 (fat thickness = 6.8 mm) and 18.9 MUM/s for subject 2 (fat thickness = 5.0 mm),
      which may be influenced by the fat thicknesses. In both subjects, DeltaHbO2 and
      DeltaHbT continued to increase for approximately another 70 s after the microwave
      antenna was switched off. 

PMID- 23852518
TI  - Oxygen-sensitive quantum dots for possible nanoscale oxygen imaging in cultured
      cells.
AB  - Quantum dots (QDs) are the semiconductor crystal with a nanometer particle size
      that emit fluorescence of a size-dependent wavelength. In this study, we examined
      whether L-cysteine-capped CdTe quantum dots (QD580, diameter ~4 nm) might be used
      as an optical probe for intracellular oxygen (O2) in cultured cells. QD580 was
      successfully introduced in cultured COS-7 cells by incubating cells with 10 nM
      QD580 for 5-60 min at 37 degrees C. Cells were exposed to 20 % O2 (0.5 h), then
      0.5 % O2 or 20 % O2 (1 h), and finally 20 % O2 (0.5 h) gases. We found
      significant increases in the fluorescence intensity at 0.5 % O2. However, when
      compared with QD580 in buffer solution, QD580 fluorescence in cells was
      considerably weak and vulnerable to repeated excitation light exposures. The
      present study demonstrated the potential of L-cysteine-capped CdTe QDs as a
      nanoscale probe for intracellular O2 in cultured cells. Further improvement of
      the QD is necessary for quantitative assessment of O2 in the cell. 

PMID- 23852519
TI  - Boron tracedrug design for neutron dynamic therapeutics for LDL.
AB  - We describe our solution for removal of the low-density lipoprotein (LDL) depot
      contained in proteins and lipids as a 'druggable' target for atherosclerotic
      cardiovascular diseases by neutron dynamic therapy (NDT), which we developed
      using boron tracedrugs for NDT against bovine serum albumin as a model protein.
      Thus, we examined, among our developed boron tracedrugs, a boron-containing
      curcuminoid derivative UTX-51, to destroy freshly isolated human LDL dynamically
      under irradiated thermal neutron to obtain a decreased intensity of band of LDL
      treated with UTX-51 and thermal neutron irradiation in their SDS-PAGE and
      electrophoresis analysis. These results suggest that UTX-51 might be a novel
      candidate of 'beyond chemical' therapeutic agents for atherosclerotic
      cardiovascular disease. 

PMID- 23852520
TI  - New method of analyzing NIRS data from prefrontal cortex at rest.
AB  - The aim of this study was to develop a simple technique for objective assessment
      of mental stress levels by measuring hemoglobin concentration changes in the
      bilateral prefrontal cortex (PFC) at rest, employing two-channel near-infrared
      spectroscopy (NIRS). Each subject was instructed to think about nothing in
      particular for 3 min and then to complete the State-Trait Anxiety Inventory
      (STAI) test. Next, NIRS measurements were taken and the left/right asymmetry of
      PFC activity at rest was evaluated by calculating the proposed Laterality Index
      at Rest (LIR). There was a significant positive correlation between the LIR and
      STAI score in 39 subjects. The present method allowed evaluation of mental stress
      level from NIRS data in the PFC at rest. 

PMID- 23852522
TI  - Wavelength selection for the improvement of the signal-to-noise ratio for imaging
      of haemoglobin oxygenation with RGB reflectometry.
AB  - We demonstrate the optimisation of wavelengths for the imaging of cortical
      haemoglobin oxygenation with broadband RGB reflectometry. Wavelengths were chosen
      in order to minimise the likely crosstalk and optimise the signal-to-noise ratio
      by simulating effects of different combinations of wavelengths on the condition
      number of the resulting extinction coefficient matrices. The results obtained
      were evaluated experimentally for four combinations of commercially available LED
      combinations and compared with data from the literature. 

PMID- 23852521
TI  - Radiation oxygen biology with pulse electron paramagnetic resonance imaging in
      animal tumors.
AB  - The reduced oxygen in tumors (hypoxia) generates radiation resistance and limits
      tumor control probability (TCP) at radiation doses without significant normal
      tissue complication. Modern radiation therapy delivery with intensity-modulated
      radiation therapy (IMRT) enables complex, high-dose gradient patterns, which
      avoid sensitive human tissues and organs. EPR oxygen images may allow selection
      of more resistant parts of a tumor to which to deliver more radiation dose to
      enhance TCP. EPR O2 images are obtained using injected narrow-line, low
      relaxation rate trityl spin probes that enable pulse radiofrequency EPR O2 images
      of tumors in the legs of mice, rats, and rabbits, the latter exceeding 4 cm in
      size. Low relaxation rates of trityls have enabled novel T1-, rather than T2-,
      based oximetry, which provides near absolute pO2 imaging. Tomographic image
      formation and filtered back projection reconstruction are used to generate these
      images with fixed, linear stepped gradients. Images obtained both with T2 and T1
      oximetric images have demonstrated the complex in vivo mechanism explaining the
      unexpected efficacy of TNFerade, a radiation-inducible adenoviral construct to
      locally produce TNF-induced vascular as well as radiation damage [1, 2]. The
      unexpected efficacy of large-dose radiation fractions is seen to be due to an
      interaction between host microvasculature and tumor cells producing a prompt (15
      min) postradiation hypoxia, paralyzing tumor cell repair, and sensitizing tumors.
      Finally, cure of tumors treated to a single 50 % control dose shows a significant
      dependence on EPR O2 image hypoxic fractions, best shown with the fraction of
      voxels less than 10 Torr (HF10). We show that these O2 images provide a
      quantitative basis for measuring tumor and normal tissue response to abnormally
      low O2 levels. Measurements of vascular endothelial growth factor (VEGF)
      production in a specific syngeneic mouse fibrosarcoma, FSa versus fraction of
      tissue voxels with pO2 less than 10 Torr, produced a slope of 0.14 pg VEGF
      protein/mg total protein/% HF10. We argue that this quantification may be
      diagnostic of tumor versus normal tissue, and it may be etiologic in the
      development of malignancy. 

PMID- 23852523
TI  - Improving pulse oximetry accuracy by removing motion artifacts from
      photoplethysmograms using relative sensor motion: a preliminary study.
AB  - To expand applicability of pulse oximetry in low-acuity ambulatory settings, the
      impact of motion on extracted parameters as saturation (SpO2) and pulse rate (PR)
      needs to be reduced. We hypothesized that sensor motion relative to the skin can
      be used as an artifact reference in a correlation canceller to reduce motion
      artifacts in photoplethysmograms (PPGs), in order to improve SpO2 and PR
      measurements. This has been proven true in in vivo measurements, where forehead
      PPGs have been obtained while subjects are walking on a treadmill and relative
      sensor motion has been measured via self-mixing interferometry. By using relative
      motion in a normalized least mean square algorithm, the standard deviation of
      SpO2 and PR errors is on average reduced by 31 % and 13 %, respectively. 

PMID- 23852524
TI  - Measuring the vascular diameter of brain surface and parenchymal arteries in
      awake mouse.
AB  - The present study reports a semiautomatic image analysis method for measuring the
      spatiotemporal dynamics of the vessel dilation that was fluorescently imaged with
      either confocal or two-photon microscope. With this method, arterial dilation
      induced by whisker stimulation was compared between cortical surface and
      parenchymal tissue in the vibrissae area of somatosensory cortex in awake Tie2
      GFP mice in which the vascular endothelium had genetically expressed green
      fluorescent protein. We observed that a mean arterial diameter during a pre
      stimulus baseline state was 39 +/- 7, 19 +/- 1, 16 +/- 4, 17 +/- 4, and 14 +/- 3
      MUm at depths of 0, 100, 200, 300, and 400 MUm, respectively. The stimulation
      evoked dilation induced by mechanical whisker deflection (10 Hz for 5 s) was 3.4
      +/- 0.8, 1.8 +/- 0.8, 1.8 +/- 0.9, 1.6 +/- 0.9, and 1.5 +/- 0.6 MUm at each
      depth, respectively. Consequently, no significant differences were observed for
      the vessel dilation rate between the cortical surface and parenchymal arteries:
      8.8 %, 9.9 %, 10.9 %, 9.2 %, and 10.3 % relative to their baseline diameters,
      respectively. These preliminary results demonstrate that the present method is
      useful to further investigate the quantitative relationships between the
      spatiotemporally varying arterial tone and the associated blood flow changes in
      the parenchymal microcirculation to reveal the regulatory mechanism of the
      cerebral blood flow.

PMID- 23852525
TI  - Simultaneous imaging of cortical blood flow and haemoglobin concentration with
      LASCA and RGB reflectometry.
AB  - We demonstrate a system for the simultaneous imaging of cortical blood flow and
      haemoglobin oxygenation by laser speckle contrast analysis (LASCA) and RGB
      reflectometry. The sensitivity of the system was tested by observing changes of
      haemoglobin oxygenation and blood flow in rats in response to ischaemic stroke,
      hypercapnia, hyperoxia, hypoxia, cortical spreading depression and cortical
      activation following forepaw stimulation. 

PMID- 23852526
TI  - Quality evaluation method for rat brain cryofixation on the basis of NADH
      fluorescence.
AB  - The goal of biological samples' cryofixation is to trap a metabolic state as it
      exists in vivo by rapidly stopping internal reactions. However, obtaining perfect
      quality of cryofixation for large and high hypermetabolism organ/tissue (such as
      brain, heart) remains a challenge. The aim of this study was to develop and
      display a comprehensive and direct method to evaluate cryofixation's process and
      quality. Here, we adopt a delicate combination of homemade cryo-imaging system
      with a rat cardiac arrest model that can control cryofixation time optionally. we
      successfully evaluate the cryofixation time-related nicotinamide adenine
      dinucleotide (NADH) fluorescence pattern of several coronal sections in rat's
      brain that suffered from directional funnel cryofixation procedure. Through
      quantitative analysis of the distribution map of NADH fluorescence, we could
      obtain a relationship between cryofixation time and well cryofixation volume and
      then could deduce the cryofixation rates and quality at different time points.
      Our results also demonstrated that dissection of the temporal muscle of rat could
      significantly optimize the classical direct funnel cryofixation protocol. 

PMID- 23852527
TI  - Cerebral cortex activation mapping upon electrical muscle stimulation by 32
      channel time-domain functional near-infrared spectroscopy.
AB  - The application of different EMS current thresholds on muscle activates not only
      the muscle but also peripheral sensory axons that send proprioceptive and pain
      signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was
      employed to map regional cortical activities under varied EMS current intensities
      applied on the right wrist extensor muscle. Eight healthy volunteers underwent
      four EMS at different current thresholds based on their individual maximal
      tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time
      courses of the absolute oxygenated and deoxygenated hemoglobin concentrations
      primarily over the bilateral sensorimotor cortical (SMC) regions were
      extrapolated, and cortical activation maps were determined by general linear
      model using the NIRS-SPM software. The stimulation-induced wrist extension
      paradigm significantly increased activation of the contralateral SMC region
      according to the EMS intensities, while the ipsilateral SMC region showed no
      significant changes. This could be due in part to a nociceptive response to the
      higher EMS current intensities and result also from increased sensorimotor
      integration in these cortical regions. 

PMID- 23852528
TI  - NIRS-based neurofeedback learning systems for controlling activity of the
      prefrontal cortex.
AB  - The aim of this study was to develop a NIRS-based neurofeedback system to
      modulate activity in the prefrontal cortex (PFC). We evaluated the effectiveness
      of the system in terms of separability of changes in oxy-Hb and its derivative.
      Training with neurofeedback resulted in higher separability than training without
      neurofeedback or no training, suggesting that the neurofeedback system could
      enhance self-control of PFC activity. Interestingly, the dorsolateral PFC
      exhibited enhanced activity and high separability after neurofeedback training.
      These observations suggest that the neurofeedback system might be useful for
      training subjects to regulate emotions by self-control of dorsolateral PFC
      activity. 

PMID- 23852529
TI  - Cortical mapping of 3D optical topography in infants.
AB  - Precise localisation of cortical activation in the early development of the
      infant brain remains unclear. It is challenging to co-register haemodynamic
      responses during functional activation in infants with the underlying anatomy of
      the brain. We used a multispectral imaging algorithm to reconstruct 3D optical
      topographic images of haemodynamic responses in an infant during voice
      processing. In this chapter, we present a method for co-registering 3D optical
      topography images reconstructed from functional activation data in infants onto
      anatomical brain images obtained from MRI structurals of the individual infants. 

PMID- 23852530
TI  - Monitoring of hemodynamic change in patients with carotid artery stenosis during
      the tilt test using wearable near-infrared spectroscopy.
AB  - Transient ischemic attack (TIA) is a major complication in patients with carotid
      artery stenosis. Patients with severe stenosis sometimes complain of orthostatic
      dizziness, such as syncope. The purpose of this study was to examine the
      usefulness of near-infrared spectroscopy (NIRS) for evaluating cerebral
      circulation in patients with carotid artery stenosis during head-up tilt test
      (HUTT). Fourteen patients with carotid artery stenosis and nine normal control
      subjects participated. In addition to blood pressure monitoring, hemoglobin (Hb)
      values (oxy-Hb, deoxy-Hb, and total Hb) were recorded by a wearable NIRS
      instrument with a high time resolution during HUTT. Oxy-Hb, which decreased
      initially when the test table was elevated, subsequently increased in normal
      volunteers and patients with carotid artery stenosis and did not differ
      significantly between the two groups. However, the oxy-Hb reduction in the
      carotid artery stenosis group (-0.02 +/- 0.03 a.u.) at 30 s after elevation of
      the table was significantly larger than in the normal group (0.02 +/- 0.02 a.u.,
      P < 0.01). Our results indicate that oxy-Hb reduction in patients with carotid
      artery stenosis may be related to orthostatic dizziness. We concluded that NIRS
      monitoring is useful for evaluating cerebral autoregulation in patients with
      severe carotid artery stenosis. 

PMID- 23852531
TI  - Hydrogen sulfide induces heme oxygenase-1 in human kidney cells.
AB  - Hydrogen sulfide (H2S) has been shown to have a potential protective role in a
      number of disease states including diabetes and various kidney disorders;
      however, the mechanisms involved are still unclear. The aim of this study was to
      investigate if H2S effects the expression of the antioxidant enzyme heme
      oxygenase-1 (HO-1) in human kidney cells. Human mesangial cells and human
      podocytes were cultured at normal physiological glucose concentration (5.5 mM)
      and then treated with different H2S donors for a 24-h period. Protein was then
      extracted from the cells, and the expression levels of HO-1 determined by Western
      blotting. There was a significant increase in HO-1 expression after treatment
      with the H2S donors in both mesangial and podocyte cells. These results suggest
      that H2S has a role in the regulation of HO-1 expression, and the ability to
      upregulate this antioxidant enzyme maybe a potential mechanism by which H2S
      exerts its protective effects.

PMID- 23852532
TI  - The relationship between type 2 diabetes family history, body composition and
      blood basal glycemia in sedentary people.
AB  - The aim of this study was to verify whether there is a positive correlation
      between family history to type 2 diabetes mellitus and body mass and composition,
      and alterations in blood basal glycaemia levels in sedentary male and female.
      Anthropometric variables, blood parameters, body composition and body surface
      area were evaluated on 183 male and 237 female sedentary individuals.
      Participants were classified into two groups: FH(+) (family history positive) and
      FH(-) (familiar history negative) according to their medical history. The FH(+)
      group showed higher values of body mass and body surface area than FH(-) group.
      These differences were statistically significant (p < 0.05) for the female
      subgroup. When compared to the FH(-) group, FH(+) female individuals showed a
      significantly greater fat mass (p < 0.01) and a significantly lower free fat mass
      to-fat mass ratio (FFM/FM ratio) (p < 0.05). FH(+) female individuals showed
      significant lower levels of basal glucose values for Kg of FFM (p < 0.05), FM (p
      < 0.01) and BSA (p < 0.01) than FH(-) group. The results of this study indicate
      that body mass and composition correlate positively to family history to type 2
      diabetes. The relationship between family history and body composition is
      particularly evident in young FH(+) female. Thus, as family history might
      represent a risk factor for the development of type 2 diabetes, this could be
      considered as an important parameter able to predict the onset of the disease
      itself. This knowledge could be used to improve preventive interventions (i.e.
      increasing levels of physical activity) promoting healthy lifestyle.

PMID- 23852533
TI  - Targeting acute myeloid leukemia with a proapoptotic peptide conjugated to a Toll
      like receptor 2-mediated cell-penetrating peptide.
AB  - Cell-penetrating peptides provide a unique platform to create a new generation of
      cancer therapeutics with enhanced efficacy and diminished toxicity. In our study,
      enhanced expression of toll-like receptor 2 (TLR2) was observed in acute myeloid
      leukemia (AML) cells. Screening of a phage display peptide library using
      Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL)
      identified a TLR2-binding peptide motif, Pep2. We show that the TLR2-binding
      peptide motif targeted and penetrated into leukemia cells in a TLR2-dependent
      manner. Moreover, a synthetic, chimeric peptide composed of the TLR2-binding
      motif linked to a programmed cell death-inducing sequence, D(KLAKLAK)2, induced
      apoptosis in AML cells with high TLR2 expression (TLR2(high)) but not in chronic
      myeloid leukemia (CML) cells with low TLR2 expression (TLR2(low)). The
      antileukemia activity of this chimeric peptide was confirmed in leukemia patient
      samples and an animal model of myeloid leukemia, as the development of leukemia
      was significantly delayed in mice with TLR2(high) AML compared to TLR2(low) CML
      NOD/SCID mice. TUNEL assays on bone marrow tissue slices revealed that the
      chimerical peptide induced leukemia cell apoptosis in a TLR2-dependent manner.
      Together, our findings indicate that TLR2 is a potential therapeutic target for
      the prevention and treatment of AML, and the prototype, Pep2-D(KLAKLAK)2, is a
      promising drug candidate in this setting.

PMID- 23852534
TI  - Dye removal using modified copper ferrite nanoparticle and RSM analysis.
AB  - In this paper, copper ferrite nanoparticle (CFN) was synthesized, modified by
      cetyl trimethylammonium bromide, and characterized. Dye removal ability of the
      surface modified copper ferrite nanoparticle (SMCFN) from single system was
      investigated. The physical characteristics of SMCFN were studied using Fourier
      transform infrared, scanning electron microscopy, and X-ray diffraction. Acid
      Blue 92, Direct Green 6, Direct Red 23, and Direct Red 80 were used as model
      compounds. The effect of operational parameters (surfactant concentration,
      adsorbent dosage, dye concentration, and pH) on dye removal was evaluated.
      Response surface methodology (RSM) was used for the analysis of the dye removal
      data. The experimental checking in these optimal conditions confirms good
      agreements with RSM results. The results showed that the SMCFN being a magnetic
      adsorbent might be a suitable alternative to remove dyes from colored aqueous
      solutions. 

PMID- 23852535
TI  - Effectiveness and potential ecological effects of offshore surface dispersant use
      during the Deepwater Horizon oil spill: a retrospective analysis of monitoring
      data.
AB  - The Special Monitoring of Applied Response Technologies (SMART) program was used
      during the Deepwater Horizon oil spill as a strategy to monitor the effectiveness
      of sea surface dispersant use. Although SMART was implemented during aerial and
      vessel dispersant applications, this analysis centers on the effort of a special
      dispersant missions onboard the M/V International Peace, which evaluated the
      effectiveness of surface dispersant applications by vessel only. Water samples (n
      = 120) were collected from background sites, and under naturally and chemically
      dispersed oil slicks, and were analyzed for polycyclic aromatic hydrocarbons
      (TPAHs), total petroleum hydrocarbons (TPH), and a chemical marker of Corexit
      (dipropylene glycol n-butyl ether, DPnB). Water chemistry results were analyzed
      relative to SMART field assessments of dispersant effectiveness ("not effective,"
      "effective," and "very effective"), based on in situ fluorometry. Chemistry data
      were also used to indirectly determine if the use of dispersants increased the
      risk of acute effects to water column biota, by comparison to toxicity
      benchmarks. TPAH and TPH concentrations in background, and naturally and
      chemically dispersed samples were extremely variable, and differences were not
      statistically detected across sample types. Ratios of TPAH and TPH between
      chemically and naturally dispersed samples provided a quantitative measure of
      dispersant effectiveness over natural oil dispersion alone, and were in
      reasonable agreement with SMART field assessments of dispersant effectiveness.
      Samples from "effective" and "very effective" dispersant applications had ratios
      of TPAH and TPH up to 35 and 64, respectively. In two samples from an "effective"
      dispersant application, TPHs and TPAHs exceeded acute benchmarks (0.81 mg/L and 8
      MUg/L, respectively), while none exceeded DPnB's chronic value (1,000 MUg/L).
      Although the primary goal of the SMART program is to provide near real-time
      effectiveness data to the response, and not to address concerns regarding acute
      biological effects, the analyses presented here demonstrate that SMART can
      generate information of value to a larger scientific audience. A series of
      recommendations for future SMART planning are also provided.

PMID- 23852536
TI  - A systems approach to modeling Community-Based Environmental Monitoring: a case
      of participatory water quality monitoring in rural Mexico.
AB  - Community-Based Environmental Monitoring (CBM) is a social practice that makes a
      valuable contribution to environmental management and construction of active
      societies for sustainable future. However, its documentation and analysis show
      deficiencies that hinder contrast and comparison of processes and effects. Based
      on systems approach, this article presents a model of CBM to orient assessment of
      programs, with heuristic or practical goals. In a focal level, the model
      comprises three components, the social subject, the object of monitoring, and the
      means of action, and five processes, data management, social learning,
      assimilation/decision making, direct action, and linking. Emergent properties
      were also identified in the focal and suprafocal levels considering community
      self-organization, response capacity, and autonomy for environmental management.
      The model was applied to the assessment of a CBM program of water quality
      implemented in rural areas in Mexico. Attributes and variables (indicators) for
      components, processes, and emergent properties were selected to measure changes
      that emerged since the program implementation. The assessment of the first 3
      years (2010-2012) detected changes that indicated movement towards the expected
      results, but it revealed also the need to adjust the intervention strategy and
      procedures. Components and processes of the model reflected relevant aspects of
      the CBM in real world. The component called means of action as a key element to
      transit "from the data to the action." The CBM model offered a conceptual
      framework with advantages to understand CBM as a socioecological event and to
      strengthen its implementation under different conditions and contexts.

PMID- 23852537
TI  - Notch1-induced brain tumor models the sonic hedgehog subgroup of human
      medulloblastoma.
AB  - While activation of the Notch pathway is observed in many human cancers, it is
      unknown whether elevated Notch1 expression is sufficient to initiate
      tumorigenesis in most tissues. To test the oncogenic potential of Notch1 in solid
      tumors, we expressed an activated form of Notch1 (N1ICD) in the developing mouse
      brain. N1ICD;hGFAP-cre mice were viable but developed severe ataxia and seizures,
      and died by weaning age. Analysis of transgenic embryo brains revealed that N1ICD
      expression induced p53-dependent apoptosis. When apoptosis was blocked by genetic
      deletion of p53, 30% to 40% of N1ICD;GFAP-cre;p53(+/-) and N1ICD;GFAP-cre;p53(-/
      ) mice developed spontaneous medulloblastomas. Interestingly, N1ICD-induced
      medulloblastomas most closely resembled the sonic hedgehog subgroup of human
      medulloblastoma at the molecular level. Surprisingly, N1ICD-induced tumors do not
      maintain high levels of the Notch pathway gene expression, except for Notch2,
      showing that initiating oncogenic events may not be decipherable by analyzing
      growing tumors in some cases. In summary, this study shows that Notch1 has an
      oncogenic potential in the brain when combined with other oncogenic hits, such as
      p53 loss, and provides a novel mouse model of medulloblastoma. Cancer Res;
      73(17); 5381-90. (c)2013 AACR. 

PMID- 23852538
TI  - A role for the endothelium in vascular calcification.
AB  - RATIONALE: Vascular calcification is a regulated process that involves
      osteoprogenitor cells and frequently complicates common vascular disease, such as
      atherosclerosis and diabetic vasculopathy. However, it is not clear whether the
      vascular endothelium has a role in contributing osteoprogenitor cells to the
      calcific lesions. OBJECTIVE: To determine whether the vascular endothelium
      contributes osteoprogenitor cells to vascular calcification. METHODS AND RESULTS:
      In this study, we use 2 mouse models of vascular calcification, mice with gene
      deletion of matrix Gla protein, a bone morphogenetic protein (BMP)-inhibitor, and
      Ins2Akita/+ mice, a diabetes model. We show that enhanced BMP signaling in both
      types of mice stimulates the vascular endothelium to contribute osteoprogenitor
      cells to the vascular calcification. The enhanced BMP signaling results in
      endothelial-mesenchymal transitions and the emergence of multipotent cells,
      followed by osteoinduction. Endothelial markers colocalize with multipotent and
      osteogenic markers in calcified arteries by immunostaining and fluorescence
      activated cell sorting. Lineage tracing using Tie2-Gfp transgenic mice supports
      an endothelial origin of the osteogenic cells. Enhancement of matrix Gla protein
      expression in Ins2Akita/+ mice, as mediated by an Mgp transgene, limits the
      generation of multipotent cells. Moreover, matrix Gla protein-depleted human
      aortic endothelial cells in vitro acquire multipotency rendering the cells
      susceptible to osteoinduction by BMP and high glucose. CONCLUSIONS: Our data
      suggest that the endothelium is a source of osteoprogenitor cells in vascular
      calcification that occurs in disorders with high BMP activation, such as
      deficiency of BMP-inhibitors and diabetes mellitus.

PMID- 23852539
TI  - An endogenously produced fragment of cardiac myosin-binding protein C is
      pathogenic and can lead to heart failure.
AB  - RATIONALE: A stable 40-kDa fragment is produced from cardiac myosin-binding
      protein C when the heart is stressed using a stimulus, such as ischemia
      reperfusion injury. Elevated levels of the fragment can be detected in the
      diseased mouse and human heart, but its ability to interfere with normal cardiac
      function in the intact animal is unexplored. OBJECTIVE: To understand the
      potential pathogenicity of the 40-kDa fragment in vivo and to investigate the
      molecular pathways that could be targeted for potential therapeutic intervention.
      METHODS AND RESULTS: We generated cardiac myocyte-specific transgenic mice using
      a Tet-Off inducible system to permit controlled expression of the 40-kDa fragment
      in cardiomyocytes. When expression of the 40-kDa protein is induced by crossing
      the responder animals with tetracycline transactivator mice under conditions in
      which substantial quantities approximating those observed in diseased hearts are
      reached, the double-transgenic mice subsequently experience development of
      sarcomere dysgenesis and altered cardiac geometry, and the heart fails between 12
      and 17 weeks of age. The induced double-transgenic mice had development of
      cardiac hypertrophy with myofibrillar disarray and fibrosis, in addition to
      activation of pathogenic MEK-ERK pathways. Inhibition of MEK-ERK signaling was
      achieved by injection of the mitogen-activated protein kinase (MAPK)/ERK
      inhibitor U0126. The drug effectively improved cardiac function, normalized heart
      size, and increased probability of survival. CONCLUSIONS: These results suggest
      that the 40-kDa cardiac myosin-binding protein C fragment, which is produced at
      elevated levels during human cardiac disease, is a pathogenic fragment that is
      sufficient to cause hypertrophic cardiomyopathy and heart failure.

PMID- 23852540
TI  - Annular erythema and photosensitivity as manifestations of efavirenz-induced
      cutaneous reactions: a review of five consecutive cases.
AB  - OBJECTIVES: In HIV-infected persons, a rash is the most common manifestation of
      drug hypersensitivity reactions. Non-nucleotide reverse transcriptase inhibitors
      are a major cause of cutaneous reactions. While the characteristics of nevirapine
      associated cutaneous adverse drug reactions (CADRs) have been well described,
      there are limited data on efavirenz-associated CADRs. The objective of this study
      was to characterize the clinical features of consecutive cases of efavirenz
      associated CADRs in a single referral centre diagnosed over a 3 year period.
      METHODS: We retrospectively reviewed the clinical records of 231 patients
      admitted with CADRs to a tertiary dermatology ward in Cape Town, South Africa.
      RESULTS: In 42/231(18%) cases, there had been exposure to efavirenz in the
      preceding 8 weeks. Of these, 5/42 (12%) patients were diagnosed with probable
      efavirenz-associated CADRs based on the Naranjo score. The median exposure to
      efavirenz before the onset of the rash was 12 days (range 2-48). All the patients
      were female, with a median age of 31 years and a median CD4 cell count of 300
      cells/mm(3) (range 81-887). Four had a photo-distributed eruption and one had a
      confluent indurated erythema affecting the face, trunk and limbs. In three out of
      five cases, there were annular plaques with raised erythematous edges and dusky
      centres, which were photo-distributed. Two patients had a mild transaminitis and
      another a mild eosinophilia. Histological features were non-specific, with
      perivascular lymphocytes the only consistent feature. In all five cases,
      efavirenz was withdrawn and potent topical steroid was the only CADR-specific
      intervention. The eruptions resolved on discharge from hospital, with no sequelae
      except for residual post-inflammatory hyperpigmentation. CONCLUSIONS: Photo
      distribution and annular erythema should alert clinicians to the possibility of
      efavirenz-associated CADRs.

PMID- 23852541
TI  - Characterization of blaCTX-M IncFII plasmids and clones of Escherichia coli from
      pets in France.
AB  - OBJECTIVES: To characterize bla(CTX-M) IncFII plasmids and clones of Escherichia
      coli from cats and dogs and to compare them with bla(CTX-M) IncFII plasmids
      reported in humans. METHODS: From December 2006 to April 2010, 518 E. coli
      isolates from clinical infections in cats and dogs were screened for extended
      spectrum beta-lactamase (ESBL) production. Antimicrobial susceptibility was
      performed by disc diffusion and resistance genes were identified by PCR and
      sequencing. Plasmids were characterized using PCR-based replicon typing and sub
      typing schemes, restriction fragment length polymorphism analysis, S1-PFGE and
      Southern hybridization. Isolates were characterized by PFGE, phylogenetic
      grouping, O25b typing and multilocus sequence typing. RESULTS: Nineteen E. coli
      isolates (3.7%) produced ESBLs, of which 14 (74%) carried bla(CTX-M) IncFII
      plasmids. The bla(CTX-M) gene was predominant and located on F31:A4:B1, F36:A4:B1
      or F36:A1:B20 plasmids, abundantly reported in humans. The bla(CTX-M) F22:A1:B20
      or F2:A2:B20 plasmids were also found. Different sequence types (STs) were
      identified, such as ST10, ST410, ST359, ST617 and ST224. Only one E. coli isolate
      belonged to the ST131 E. coli clone and carried a bla(CTX-M) F2:A2:B20 plasmid.
      CONCLUSIONS: This is the first known extensive study on ESBL-producing E. coli
      isolates from pets in France. The ST131 clone was rare. However, the predominance
      of human-like bla(CTX-M) IncFII plasmids suggests exchanges of these plasmids
      with the human reservoir.

PMID- 23852542
TI  - Genome-wide expression analysis of HSP70 family genes in rice and identification
      of a cytosolic HSP70 gene highly induced under heat stress.
AB  - The heat shock protein 70 (HSP70) gene family plays a key role in protecting
      plant cells or tissues from thermal or oxidative stress. Although many studies
      have elucidated the molecular functions of individual family members, genome-wide
      analysis of this family is still limited, especially for crop species. Our
      objective was to integrate various meta-profiling data into the context of a
      phylogenetic tree, which would enable us to perform fine evaluation of functional
      dominancy or redundancy within this family. Our data indicated that a loss-of
      function mutant of a rice cytosolic HSP70 gene (OsctHSP70-1) did not show a clear
      defective phenotype in response to high temperature because of the existence of
      another gene family member that was closely clustered with OsctHSP70-1 and had
      similar expression patterns. Moreover, the second gene showed much stronger
      anatomical expression. We indirectly analyzed the function of OsctHSP70-1 by
      studying GUS activity under the control of the endogenous promoter. We also
      designed a probable interaction network mediated by OsctHSP70-1 and used co
      expression analysis among its components to refine the network, suggesting more
      probable model to explain the function of OsctHSP70-1. 

PMID- 23852545
TI  - Size-dependent magnetophoresis of native single super-paramagnetic nanoparticles
      in a microchip.
AB  - Real-time dynamics of native super-paramagnetic nanoparticles (SPMNPs) with
      different sizes were observed in a microchip at the single-particle level. Based
      on the optimized magnetic field conditions obtained in the single-nanoparticle
      study, the SPMNPs were successfully separated and detected within ~15 s from the
      model polydisperse mixture.

PMID- 23852543
TI  - The therapeutic potential of GPR43: a novel role in modulating metabolic health.
AB  - GPR43 is a receptor for short-chain fatty acids. Preliminary data suggest a
      putative role for GPR43 in regulating systemic health via processes including
      inflammation, carcinogenesis, gastrointestinal function, and adipogenesis. GPR43
      is involved in secretion of gastrointestinal peptides, which regulate appetite
      and gastrointestinal motility. This suggests GPR43 may have a role in weight
      control. Moreover, GPR43 regulates plasma lipid profile and inflammatory
      processes, which further indicates that GPR43 could have the ability to modulate
      the etiology and pathogenesis of metabolic diseases such as obesity, type 2
      diabetes mellitus, and cardiovascular disease. This review summarizes the current
      evidence regarding the ability of GPR43 to mediate both systemic and tissue
      specific functions and how GPR43 may be modulated in the treatment of metabolic
      disease. 

PMID- 23852544
TI  - The unique features of follicular T cell subsets.
AB  - The germinal center (GC) reaction is critical for humoral immunity, but also
      contributes adversely to a variety of autoimmune diseases. While the major
      protective function of GCs is mediated by plasma cells and memory B cells,
      follicular helper T (TFH) cells represent a specialized T cell subset that
      provides essential help to the antigen-specific B cells in the form of membrane
      bound ligands and secreted factors such as IL-21. Recent studies have revealed
      that TFH cells are capable of considerable functional diversity as well as
      possessing the ability to form memory cells. The molecular basis of this
      plasticity and heterogeneity is only now emerging. It has also become apparent
      that several other populations of follicular T cells exist, including natural
      killer T cells and regulatory T cells. In this review we will discuss the
      function of follicular T cells and interaction of these populations within the GC
      response. 

PMID- 23852546
TI  - mTOR kinase inhibitor sensitizes T-cell lymphoblastic leukemia for chemotherapy
      induced DNA damage via suppressing FANCD2 expression.

PMID- 23852548
TI  - SoC CMOS UWB Pulse Radar Sensor for Contactless Respiratory Rate Monitoring.
AB  - An ultra wideband (UWB) system-on-chip radar sensor for respiratory rate
      monitoring has been realized in 90 nm CMOS technology and characterized
      experimentally. The radar testchip has been applied to the contactless detection
      of the respiration activity of adult and baby. The field operational tests
      demonstrate that the UWB radar sensor detects the respiratory rate of person
      under test (adult and baby) associated with sub-centimeter chest movements,
      allowing the continuous-time non-invasive monitoring of hospital patients and
      other people at risk of obstructive apneas such as babies in cot beds, or other
      respiratory diseases. 

PMID- 23852547
TI  - Hematopoietic progenitor cell collection after autologous transplant for multiple
      myeloma: low platelet count predicts for poor collection and sole use of
      resulting graft enhances risk of myelodysplasia.
AB  - Collection of hematopoietic progenitor cells (HPC) after previous autologous
      hematopoietic progenitor cell transplant (aHCT) was studied in 221 patients with
      multiple myeloma (MM). With a total of 333 collections, the median number of
      CD34+ cells collected was 4.7 * 10(6) CD34+ cells/kg, and 74% of the patients
      collected >= 2.5 * 10(6) CD34+ cells/kg. Among 26 variables examined, the
      strongest predictor for poor collection was a platelet count <100 * 10(6)/l
      before mobilization (P<0.001). A subsequent aHCT was performed in 154 of the 221
      patients. Sole use of HPC procured after aHCT in 86 patients was associated with
      delayed platelet recovery (P<0.001) and linked to development of myelodysplastic
      syndrome (MDS)-associated cytogenetic abnormalities (MDS-CA; P=0.027, odds ratio
      (OR) 10.34) and a tendency towards clinical MDS/acute myeloid leukemia (AML;
      P=0.091, OR 3.57). However, treatment-related mortality (P=0.766) and time to
      absolute neutrophil count recovery >=0.5 * 10(9)/l (P=0.879) were similar to when
      a pre-aHCT graft was used. Indeed, adding HPC collected before any aHCT
      neutralized the risk of MDS-CA or MDS/AML. Therefore, we advise generous initial
      HPC collection to broaden the salvage armamentarium for patients with MM.

PMID- 23852549
TI  - A Programmable Implantable Microstimulator SoC With Wireless Telemetry:
      Application in Closed-Loop Endocardial Stimulation for Cardiac Pacemaker.
AB  - A low-power, wireless, and implantable microstimulator system on chip with smart
      powering management, immediate neural signal acquisition, and wireless
      rechargeable system is proposed. A system controller with parity checking handles
      the adjustable stimulus parameters for the stimulated objective. In the current
      paper, the rat's intra-cardiac electrogram is employed as the stimulated model in
      the animal study, and it is sensed by a low-voltage and low-power monitoring
      analog front end. The power management unit, which includes a rectifier, battery
      charging and detection, and a regulator, is used for the power control of the
      internal circuits. The stimulation data and required clock are extracted by a
      phase-locked-loop-based phase shift keying demodulator from an inductive AC
      signal. The full chip, which consumes 48 MUW only, is fabricated in a TSMC 0.35
      MUm 2P4M standard CMOS process to perform the monitoring and pacing functions
      with inductively powered communication in the in vivo study. 

PMID- 23852550
TI  - A 2.4 GHz ULP OOK Single-Chip Transceiver for Healthcare Applications.
AB  - This paper describes an ultra-low power (ULP) single chip transceiver for
      wireless body area network (WBAN) applications. It supports on-off keying (OOK)
      modulation, and it operates in the 2.36-2.4 GHz medical BAN and 2.4-2.485 GHz ISM
      bands. It is implemented in 90 nm CMOS technology. The direct modulated
      transmitter transmits OOK signal with 0 dBm peak power, and it consumes 2.59 mW
      with 50% OOK. The transmitter front-end supports up to 10 Mbps. The transmitter
      digital baseband enables digital pulse-shaping to improve spectrum efficiency.
      The super-regenerative receiver front-end supports up to 5 Mbps with -75 dBm
      sensitivity. Including the digital part, the receiver consumes 715 MUW at 1 Mbps
      data rate, oversampled at 3 MHz. At the system level the transceiver achieves
      PER=10 (-2) at 25 meters line of site with 62.5 kbps data rate and 288 bits
      packet size. The transceiver is integrated in an electrocardiogram (ECG) necklace
      to monitor the heart's electrical property. 

PMID- 23852551
TI  - A CMOS Energy Harvesting and Imaging (EHI) Active Pixel Sensor (APS) Imager for
      Retinal Prosthesis.
AB  - A CMOS image sensor capable of imaging and energy harvesting on same focal plane
      is presented for retinal prosthesis. The energy harvesting and imaging (EHI)
      active pixel sensor (APS) imager was designed, fabricated, and tested in a
      standard 0.5 MUm CMOS process. It has 54 * 50 array of 21 * 21 MUm(2) EHI pixels,
      10-bit supply boosted (SB) SAR ADC, and charge pump circuits consuming only 14.25
      MUW from 1.2 V and running at 7.4 frames per second. The supply boosting
      technique (SBT) is used in an analog signal chain of the EHI imager. Harvested
      solar energy on focal plane is stored on an off-chip capacitor with the help of a
      charge pump circuit with better than 70% efficiency. Energy harvesting efficiency
      of the EHI pixel was measured at different light levels. It was 9.4% while
      producing 0.41 V open circuit voltage. The EHI imager delivers 3.35 MUW of power
      was delivered to a resistive load at maximum power point operation. The measured
      pixel array figure of merit (FoM) was 1.32 pW/frame/pixel while imager figure of
      merit (iFoM) including whole chip power consumption was 696 fJ/pixel/code for the
      EHI imager. 

PMID- 23852552
TI  - An ultra low energy biomedical signal processing system operating at near
      threshold.
AB  - This paper presents a voltage-scalable digital signal processing system designed
      for the use in a wireless sensor node (WSN) for ambulatory monitoring of
      biomedical signals. To fulfill the requirements of ambulatory monitoring, power
      consumption, which directly translates to the WSN battery lifetime and size, must
      be kept as low as possible. The proposed processing platform is an event-driven
      system with resources to run applications with different degrees of complexity in
      an energy-aware way. The architecture uses effective system partitioning to
      enable duty cycling, single instruction multiple data (SIMD) instructions, power
      gating, voltage scaling, multiple clock domains, multiple voltage domains, and
      extensive clock gating. It provides an alternative processing platform where the
      power and performance can be scaled to adapt to the application need. A case
      study on a continuous wavelet transform (CWT)-based heart-beat detection shows
      that the platform not only preserves the sensitivity and positive predictivity of
      the algorithm but also achieves the lowest energy/sample for ElectroCardioGram
      (ECG) heart-beat detection publicly reported today. 

PMID- 23852553
TI  - A 160 MUW 8-Channel Active Electrode System for EEG Monitoring.
AB  - This paper presents an active electrode system for gel-free biopotential EEG
      signal acquisition. The system consists of front-end chopper amplifiers and a
      back-end common-mode feedback (CMFB) circuit. The front-end AC-coupled chopper
      amplifier employs input impedance boosting and digitally-assisted offset
      trimming. The former increases the input impedance of the active electrode to 2
      GOmega at 1 Hz and the latter limits the chopping induced output ripple and
      residual offset to 2 mV and 20 mV, respectively. Thanks to chopper stabilization,
      the active electrode achieves 0.8 MUVrms (0.5-100 Hz) input referred noise. The
      use of a back-end CMFB circuit further improves the CMRR of the active electrode
      readout to 82 dB at 50 Hz. Both front-end and back-end circuits are implemented
      in a 0.18 MUm CMOS process and the total current consumption of an 8-channel
      readout system is 88 MUA from 1.8 V supply. EEG measurements using the proposed
      active electrode system demonstrate its benefits compared to passive electrode
      systems, namely reduced sensitivity to cable motion artifacts and mains
      interference. 

PMID- 23852554
TI  - A novel low-power-implantable epileptic seizure-onset detector.
AB  - A novel implantable low-power integrated circuit is proposed for real-time
      epileptic seizure detection. The presented chip is part of an epilepsy prosthesis
      device that triggers focal treatment to disrupt seizure progression. The proposed
      chip integrates a front-end preamplifier, voltage-level detectors, digital
      demodulators, and a high-frequency detector. The preamplifier uses a new chopper
      stabilizer topology that reduces instrumentation low-frequency and ripple noises
      by modulating the signal in the analog domain and demodulating it in the digital
      domain. Moreover, each voltage-level detector consists of an ultra-low-power
      comparator with an adjustable threshold voltage. The digitally integrated high
      frequency detector is tunable to recognize the high-frequency activities for the
      unique detection of seizure patterns specific to each patient. The digitally
      controlled circuits perform accurate seizure detection. A mathematical model of
      the proposed seizure detection algorithm was validated in Matlab and circuits
      were implemented in a 2 mm(2) chip using the CMOS 0.18- MUm process. The proposed
      detector was tested by using intracerebral electroencephalography (icEEG)
      recordings from seven patients with drug-resistant epilepsy. The seizure signals
      were assessed by the proposed detector and the average seizure detection delay
      was 13.5 s, well before the onset of clinical manifestations. The measured total
      power consumption of the detector is 51 MUW. 

PMID- 23852555
TI  - A low-power 32-channel digitally programmable neural recording integrated
      circuit.
AB  - We report the design of an ultra-low-power 32-channel neural-recording integrated
      circuit (chip) in a 0.18 MU m CMOS technology. The chip consists of eight neural
      recording modules where each module contains four neural amplifiers, an analog
      multiplexer, an A/D converter, and a serial programming interface. Each amplifier
      can be programmed to record either spikes or LFPs with a programmable gain from
      49-66 dB. To minimize the total power consumption, an adaptive-biasing scheme is
      utilized to adjust each amplifier's input-referred noise to suit the background
      noise at the recording site. The amplifier's input-referred noise can be adjusted
      from 11.2 MUVrms (total power of 5.4 MUW) down to 5.4 MUVrms (total power of 20
      MUW) in the spike-recording setting. The ADC in each recording module digitizes
      the a.c. signal input to each amplifier at 8-bit precision with a sampling rate
      of 31.25 kS/s per channel, with an average power consumption of 483 nW per
      channel, and, because of a.c. coupling, allows d.c. operation over a wide dynamic
      range. It achieves an ENOB of 7.65, resulting in a net efficiency of 77 fJ/State,
      making it one of the most energy-efficient designs for neural recording
      applications. The presented chip was successfully tested in an in vivo wireless
      recording experiment from a behaving primate with an average power dissipation
      per channel of 10.1 MU W. The neural amplifier and the ADC occupy areas of 0.03
      mm(2) and 0.02 mm(2) respectively, making our design simultaneously area
      efficient and power efficient, thus enabling scaling to high channel-count
      systems. 

PMID- 23852556
TI  - Postoperative intussusceptions in children and infants: a systematic review.
AB  - BACKGROUND: Postoperative intussusception (POI) is an unusual complication in
      children and infants who underwent various kinds of surgery. The early
      recognition was difficult for its rarity and atypical presentations. This study
      evaluates the clinical features of POI through a literature review. METHODS:
      MEDLINE database was searched for relevant articles that reported the children
      and infants with POI since 1990 in English-language using the key word
      "postoperative intussusception". All published studies containing clinical data
      for POI in children and infants were included. Reference lists of retrieved
      articles were reviewed for additional cases. Detailed data of the included cases
      were extracted and analyzed. RESULTS: Twenty-six studies with total 127 cases of
      POI were included. According to the extracted data, the median age was 19 months
      with the male-to-female ratio 1.5:1. There were 65 operations (51.2 %) that
      involved gastrointestinal system, 26 cases (20.5 %) of retroperitoneal tumor
      resection, 12 operations (9.4 %) involved diaphragm, 8 operations (6.3 %)
      involved urinary system, 5 cases (3.9 %) of partial pancreatectomy, 11 cases (8.7
      %) of non-abdominal operations. 75.5 % presented symptoms in the first 7 days
      after surgery. The prominent symptom was bilious vomiting or increased
      nasogastric output (87.1 % of 101 patients), following abdominal distention (74.3
      %), abdominal pain (35.6 %). Six cases (5.0 %) of ileocolic POI were reduced
      successfully by air enema. The small bowel intussusception attributed 85.6 % of
      POI (95 patients). Laparotomy and manual reduction were performed in 104 cases
      (86.0 %). Nine patients (7.4 %) underwent intestinal resection and anastomosis.
      CONCLUSIONS: POI should be suspected in pediatric surgical patients who showed
      signs of intestinal obstruction in the early postoperative period. Early
      recognition and prompt management are important.

PMID- 23852557
TI  - Brain oscillations and electroencephalography scalp networks during tempo
      perception.
AB  - In the current study we used electroencephalography (EEG) to investigate the
      relation between musical tempo perception and the oscillatory activity in
      specific brain regions, and the scalp EEG networks in the theta, alpha, and beta
      bands. The results showed that the theta power at the frontal midline decreased
      with increased arousal level related to tempo. The alpha power induced by
      original music at the bilateral occipital-parietal regions was stronger than that
      by tempo-transformed music. The beta power did not change with tempo. At the
      network level, the original music-related alpha network had high global
      efficiency and the optimal path length. This study was the first to use EEG to
      investigate multi-oscillatory activities and the data support the tempo-specific
      timing hypothesis. 

PMID- 23852558
TI  - Protective effects of Batroxobin on spinal cord injury in rats.
AB  - Expansion of the secondary injury following primary spinal cord injury is a major
      pathological event that increases destruction in the spinal cord, so measures to
      reduce secondary injury are needed. Our previous study demonstrated that, at the
      front of the expanding secondary injury in the spinal cord, there is an ischemic
      area in which many neurons can still be rescued. Therefore, enhancement of blood
      circulation in the cord may be helpful, and indeed, we found that a traditional
      Chinese medicine, shu-xue-tong, efficiently reduces the secondary injury. The aim
      of the present study was to investigate the effect of reducing fibrinogen with
      Batroxobin, a drug widely used clinically for ischemia, in rats with spinal cord
      contusion. We found that both 2 and 4 Batroxobin units (BU)/kg efficiently
      decreased the plasma fibrinogen, and 2 BU/kg significantly increased spinal blood
      flow, enhanced neuronal survival, mitigated astrocyte and microglia activation,
      and improved locomotor recovery. However, 4 BU/kg had no effect on the secondary
      spinal cord injury. These data suggest that Batroxobin has multiple beneficial
      effects on spinal cord injury, indicating a potential clinical application. 

PMID- 23852559
TI  - Valproic acid reduces autophagy and promotes functional recovery after spinal
      cord injury in rats.
AB  - Secondary damage is a critical determinant of the functional outcome in patients
      with spinal cord injury (SCI), and involves multiple mechanisms of which the most
      important is the loss of nerve cells mediated by multiple factors. Autophagy can
      result in cell death, and plays a key role in the development of SCI. It has been
      recognized that valproic acid (VPA) is neuroprotective in certain experimental
      animal models, however, the levels of autophagic changes in the process of
      neuroprotection by VPA treatment following SCI are still unknown. In the present
      study, we determined the extent of autophagy after VPA treatment in a rat model
      of SCI. We found that both the mRNA and protein levels of Beclin-1 and LC3 were
      significantly increased at 1, 2, and 6 h after SCI and peaked at 2 h; however,
      Western blot showed that autophagy was markedly decreased by VPA treatment at 2 h
      post-injury. Besides, post-SCI treatment with VPA improved the Basso-Beattie
      Bresnahan scale, increased the number of ventral horn motoneurons, and reduced
      myelin sheath damage compared with vehicle-treated animals at 42 days after SCI.
      Together, our results demonstrated the characteristics of autophagy expression
      following SCI, and found that VPA reduced autophagy and enhanced motor function. 

PMID- 23852561
TI  - Baboons' hand preference resists to spatial factors for a communicative gesture
      but not for a simple manipulative action.
AB  - Olive baboons (Papio anubis) do acquire and use intentional requesting gestures
      in experimental contexts. Individual's hand preference for these gestures is
      consistent with that observed for typical communicative gestures, but not for
      manipulative actions. Here, we examine whether the strength of hand preference
      may also be a good marker of hemispheric specialization for communicative
      gestures, hence differing from the strength of hand preference for manipulative
      actions. We compared the consistency of individuals' hand preference with regard
      to the variation in space of either (i) a communicative partner or (ii) a food
      item to grasp using a controlled set-up. We report more consistent hand
      preference for communicative gestures than for grasping actions. Established hand
      preference in the midline was stronger for gesturing than for grasping and
      allowed to predict the consistency of hand preference across positions. We found
      no significant relation between the direction of hand preference and the task.

PMID- 23852560
TI  - What interests them in the pictures?--differences in eye-tracking between rhesus
      monkeys and humans.
AB  - Studies estimating eye movements have demonstrated that non-human primates have
      fixation patterns similar to humans at the first sight of a picture. In the
      current study, three sets of pictures containing monkeys, humans or both were
      presented to rhesus monkeys and humans. The eye movements on these pictures by
      the two species were recorded using a Tobii eye-tracking system. We found that
      monkeys paid more attention to the head and body in pictures containing monkeys,
      whereas both monkeys and humans paid more attention to the head in pictures
      containing humans. The humans always concentrated on the eyes and head in all the
      pictures, indicating the social role of facial cues in society. Although humans
      paid more attention to the hands than monkeys, both monkeys and humans were
      interested in the hands and what was being done with them in the pictures. This
      may suggest the importance and necessity of hands for survival. Finally, monkeys
      scored lower in eye-tracking when fixating on the pictures, as if they were less
      interested in looking at the screen than humans. The locations of fixation in
      monkeys may provide insight into the role of eye movements in an evolutionary
      context.

PMID- 23852562
TI  - A mitochondria-specific visible-light sensitized europium beta-diketonate complex
      with red emission.
AB  - Our recently developed Eu(3+) coordination compound, Eu(pfppd)3(tpy) [where
      Hpfppd = 4,4,5,5,5-pentafluoro-3-hydroxy-1-(phenanthren-3-yl)pentanedione and tpy
      = 2,2':6,6''-terpyridine] exhibits significant quantum yield (Phioverall = 41%)
      and long (5)D0 lifetime (880 MUs) values under biologically relevant pH
      conditions (pH = 7.4) when excited with visible light. Hence, the Eu(3+)
      luminescent complex was examined for live cell imaging using the rat embryonic
      heart cell line, H9c2. The ternary Eu(3+) complex permeates into the H9c2 cells
      and co-localises with the mitochondria, as demonstrated by counterstaining
      experiments. Furthermore, the designed Eu(3+) bioprobe remains undissociated in
      the cell medium, showed a good cell permeability and a fast cellular uptake with
      a specific localization profile. Thus it has the potential to become a time
      resolved imaging probe that is excitable in the visible-light range. 

PMID- 23852563
TI  - Incidental pineal cysts in children who undergo 3-T MRI.
AB  - BACKGROUND: Pineal cysts, both simple and complex, are commonly encountered in
      children. More cysts are being detected with MR technology; however, nearly all
      pineal cysts are benign and require no follow-up. OBJECTIVE: To discover the
      prevalence of pineal cysts in children at our institution who have undergone high
      resolution 3-T MRI. MATERIALS AND METHODS: We retrospectively reviewed 100
      consecutive 3-T brain MRIs in children ages 1 month to 17 years (mean 6.8 +/- 5.1
      years). We evaluated 3-D volumetric T1-W imaging, axial T2-W imaging, axial T2-W
      FLAIR (fluid attenuated inversion recovery) and coronal STIR (short tau inversion
      recovery) sequences. Pineal parenchymal and cyst volumes were measured in three
      planes. Cysts were analyzed for the presence and degree of complexity. RESULTS:
      Pineal cysts were present in 57% of children, with a mean maximum linear
      dimension of 4.2 mm (range 1.5-16 mm). Of these cysts, 24.6% showed thin
      septations or fluid levels reflecting complexity. None of the cysts demonstrated
      complete T2/FLAIR signal suppression. No cyst wall thickening or nodularity was
      present. There was no significant difference between the ages of children with
      and without cysts. Cysts were more commonly encountered in girls than boys (67%
      vs. 52%; P = 0.043). There was a slight trend toward increasing pineal gland
      volume with age. CONCLUSION: Pineal cysts are often present in children and can
      be incidentally detected by 3-T MRI. Characteristic-appearing pineal cysts in
      children are benign, incidental findings, for which follow-up is not required if
      there are no referable symptoms or excessive size.

PMID- 23852564
TI  - Value of adding sonoelastography to conventional ultrasound in patients with
      congenital muscular torticollis.
AB  - BACKGROUND: Sonoelastography has been utilized to evaluate various myopathies.
      However, the benefits of adding sonoelastography to conventional ultrasound (US)
      in patients with congenital muscular torticollis are unclear. OBJECTIVE: To
      evaluate the value of adding sonoelastography to conventional US in patients with
      congenital muscular torticollis. MATERIALS AND METHODS: This study included 27
      infants clinically diagnosed with congenital muscular torticollis and 17 healthy
      infants who underwent conventional US and sonoelastography. The echogenicity of
      the sternocleidomastoid muscle was assessed as isoechoic, heterogeneous,
      hyperechoic or hypoechoic compared with normal muscle. The thickness of the
      involved and contralateral sternocleidomastoid muscles was measured.
      Elastographic findings were scored from 1 (soft) to 3 (hard) by two independent
      radiologists. RESULTS: The sternocleidomastoid muscle thickness, difference and
      ratio between involved and normal sternocleidomastoid muscle thickness, and
      elastographic score differed significantly between the patient and control
      groups. Of the 27 patients, 11 had isoechoic, 5 had heterogeneous and 11 had
      hyperechoic muscles. Congenital muscular torticollis patients with isoechoic
      muscle showed significantly higher elastographic scores than the control group,
      but there were no other significant differences by conventional US. CONCLUSIONS:
      Adding sonoelastography to conventional US is helpful for the diagnosis of
      congenital muscular torticollis, especially in patients with isoechoic
      sternocleidomastoid muscle.

PMID- 23852565
TI  - More than meets the eye-myelinated axons crowd the subthalamic nucleus.
AB  - High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a
      successful treatment for patients with advanced Parkinson's disease (PD).
      Although its exact mechanism of action is unknown, it is currently believed that
      the beneficial effects of the stimulation are mediated either by alleviating
      pathological basal ganglia output patterns of activity or by activation of the
      axons of passage that arise from the cerebral cortex and other sources. In this
      study, we show that the anatomical composition of the primate STN provides a
      substrate through which DBS may elicit widespread changes in brain activity via
      stimulation of fibers of passage. Using quantitative high-resolution electron
      microscopy, we found that the primate STN is traversed by numerous myelinated
      axons, which occupy as much as 45% of its sensorimotor territory and 36% of its
      associative region. In comparison, myelinated axons occupy only 27% of the
      surface areas of the sensorimotor and associative regions of the internal segment
      of the globus pallidus (GPi), another target for therapeutic DBS in PD. We also
      noted that myelinated axons in the STN, on average, have a larger diameter than
      those in GPi, which may render them more susceptible to electrical stimulation.
      Because axons are more excitable than other neuronal elements, our findings
      support the hypothesis that STN DBS, even when carried out entirely within the
      confines of the nucleus, mediates some of its effects by activating myelinated
      axons of passage.

PMID- 23852566
TI  - Enantio- and regioselective conjugate addition of organometallic reagents to
      linear polyconjugated nitroolefins.
AB  - The copper-catalysed conjugate addition of trialkylaluminium and dialkylzinc
      reagents to polyconjugated nitroolefins (nitrodiene and nitroenyne derivatives)
      is reported. A reversed Josiphos ligand L7 allows for the selective 1,4- or 1,6
      addition with high enantioselectivities. 

PMID- 23852567
TI  - Patterns of hemispheric specialization for a communicative gesture in different
      primate species.
AB  - We review four studies investigating hand preferences for grasping versus
      pointing to objects at several spatial positions in human infants and three
      species of nonhuman primates using the same experimental setup. We expected that
      human infants and nonhuman primates present a comparable difference in their
      pattern of laterality according to tasks. We tested 6 capuchins, 6 macaques, 12
      baboons, and 10 human infants. Those studies are the first of their kind to
      examine both human infants and nonhuman primate species with the same
      communicative task. Our results show remarkable convergence in the distribution
      of hand biases of human infants, baboons and macaques on the two kinds of tasks
      and an interesting divergence between capuchins' and other species' hand
      preferences in the pointing task. They support the hypothesis that left
      lateralized language may be derived from a gestural communication system that was
      present in the common ancestor of macaques, baboons and humans.

PMID- 23852568
TI  - Novel techniques to study colonic motor function in children.
AB  - Colonic motility is an essential component of normal colonic physiology and it
      controls essential bodily functions such as stool propulsion, storage, and
      expulsion. Disordered colonic motility may present with constipation or diarrhea
      as well as associated symptoms such as bloating, gas, pain, incontinence, and
      others. In order to assess colonic motor function, practitioners may use studies
      that either investigate transit time or that evaluate peristaltic activity.
      Transit time is the result of both the effectiveness of propulsive pressures and
      the physical characteristics of the stools. Its measurement allows one to
      quantify the extent and severity of the colonic dysfunction and permits the
      assessment of response to therapy. Various methods exist to investigate colon
      transit time and motility. In this review, we will focus on newer techniques for
      these investigations, including: scintigraphic transit studies, anorectal
      manometry, colonic manometry, and studies using a wireless motility capsule. 

PMID- 23852569
TI  - Fecal microbiota transplantation: indications, methods, evidence, and future
      directions.
AB  - Fecal microbiota transplantation (FMT) has attracted great interest in recent
      years, largely due to the global Clostridium difficile infection (CDI) epidemic
      and major advances in metagenomic sequencing of the gastrointestinal (GI)
      microbiota, with growing understanding of its structure and function. FMT is now
      recommended as the most effective therapy for relapsing CDI and, with further
      refinement, may even be used in "first-time" CDI. There is interest also in other
      conditions related to GI dysbiosis--for example, inflammatory bowel disease,
      irritable bowel syndrome, obesity, and diabetes mellitus--although quality
      evidence is at present lacking. A few trials are now underway in FMT for
      ulcerative colitis. Many unanswered questions remain, including FMT methodology-
      for example, optimal route of administration, what makes a "good donor," safety
      issues, and long-term effects of FMT.

PMID- 23852570
TI  - Nutrition and acute pancreatitis: review of the literature and pediatric
      perspectives.
AB  - Acute pancreatitis is being diagnosed more frequently in pediatrics and there is
      limited published research to guide management. In contrast, multiple prospective
      studies in the adult population have resulted in significant changes in the way
      the disease is managed, especially with regard to severe disease. The nutritional
      management of pediatric acute pancreatitis appears to lag behind current adult
      recommendations, likely resulting from a lack of awareness of the adult data,
      inherent differences between pediatric and adult pancreatitis, and the paucity of
      research performed in children. The purpose of this review is to examine the
      adult literature regarding the nutritional management of acute pancreatitis and
      discuss the possible relevance of this data in the pediatric population. 

PMID- 23852572
TI  - Acclimation to a low oxygen environment alters the hematology of largemouth bass
      (Micropterus salmoides).
AB  - One of the most severe impacts of urbanization on aquatic systems is the
      increasing presence of low oxygen environments caused by anthropogenic sources of
      pollution. As urbanization increases nationally and globally, it is becoming
      exceedingly important to understand how hypoxia affects aquatic fauna, especially
      fish species. In an effort to better understand the impacts of prolonged hypoxia
      on fishes, largemouth bass were held at 3.0 and 9.0 mg L-1 for 50 days, which has
      previously shown to be temporally sufficient to impart plastic phenotypic
      changes. Following the holding period, fish from each group were subjected to a
      low dissolved oxygen (DO) challenge of 2.0 mg L-1 for 6 h, and their
      physiological and hematological parameters were compared with control fish held
      for 6 h with no change in DO. There were no differences in the physiological
      stress responses between the two holding groups; however, the low oxygen holding
      group had increased hemoglobin and hematocrit levels following the 6-h low oxygen
      challenge compared with the high oxygen group. These results suggest largemouth
      bass exposed to chronic low oxygen conditions, either naturally or
      anthropogenically, may possess a beneficial advantage of increased oxygen uptake
      capacity during periods of low oxygen.

PMID- 23852571
TI  - Colon cleansing for colonoscopy 2013: current status.
AB  - Colonoscopy requires adequate bowel cleansing to be safe and effective. There are
      a variety of options available. This review will focus on highlighting new
      products, administration techniques emphasizing the value of split-dose and same
      day regimens, safety, and options for inadequate cleansing. 

PMID- 23852573
TI  - Benchmark dose profiles for joint-action continuous data in quantitative risk
      assessment.
AB  - Benchmark analysis is a widely used tool in biomedical and environmental risk
      assessment. Therein, estimation of minimum exposure levels, called benchmark
      doses (BMDs), that induce a prespecified benchmark response (BMR) is well
      understood for the case of an adverse response to a single stimulus. For cases
      where two agents are studied in tandem, however, the benchmark approach is far
      less developed. This paper demonstrates how the benchmark modeling paradigm can
      be expanded from the single-agent setting to joint-action, two-agent studies.
      Focus is on continuous response outcomes. Extending the single-exposure setting,
      representations of risk are based on a joint-action dose-response model involving
      both agents. Based on such a model, the concept of a benchmark profile-a two
      dimensional analog of the single-dose BMD at which both agents achieve the
      specified BMR-is defined for use in quantitative risk characterization and
      assessment. 

PMID- 23852574
TI  - Brown adipose tissue mapping in rats with combined intermolecular double-quantum
      coherence and Dixon water-fat MRI.
AB  - Brown adipose tissue (BAT) is a promising therapeutic target in obesity studies.
      Recently, MRI has been proposed for the mapping of BAT. However, because of the
      limitation of spatial resolution, similar to the existing positron emission
      tomography and computed tomography techniques for BAT detection, it fails to
      distinguish BAT cells when they are mixed with other cells. In this work, a new
      MRI method is proposed, combining intermolecular double-quantum coherence and the
      chemical shift-encoded Dixon method. Its contrast depends on the water to fat
      ratio at the cellular scale, which is smaller than the imaging voxel size. The
      feasibility of this MRI method was shown with computer simulations and phantoms,
      and preliminary imaging of BAT of rats at 7 T. Both computer simulations and
      experimental results are consistent with theoretical predictions. The method
      provides a novel contrast mechanism and can map BAT distribution exclusively. In
      particular, a mixture of BAT cells and white adipose tissue cells was detected in
      an older rat, which was undetectable by other noninvasive methods. This method
      may be applicable to a wide range of uses in BAT-related studies, including the
      formation and variation of BAT.

PMID- 23852575
TI  - Tuning the density profile of surface-grafted hyaluronan and the effect of
      counter-ions.
AB  - The present paper investigates the structure and composition of grafted sodium
      hyaluronan at a solid-liquid interface using neutron reflection. The solvated
      polymer at the surface could be described with a density profile that decays
      exponentially towards the bulk solution. The density profile of the polymer
      varied depending on the deposition protocol. A single-stage deposition resulted
      in denser polymer layers, while layers created with a two-stage deposition
      process were more diffuse and had an overall lower density. Despite the diffuse
      density profile, two-stage deposition leads to a higher surface excess. Addition
      of calcium ions causes a strong collapse of the sodium hyaluronan chains,
      increasing the polymer density near the surface. This effect is more pronounced
      on the sample prepared by two-stage deposition due to the initial less dense
      profile. This study provides an understanding at a molecular level of how surface
      functionalization alters the structure and how surface layers respond to changes
      in calcium ions in the solvent. 

PMID- 23852576
TI  - Zaccai neutron resilience and site-specific hydration dynamics in a globular
      protein.
AB  - A discussion is presented of contributions of the Zaccai group to the
      understanding of flexibility in biological macromolecules using dynamic neutron
      scattering. The concept of resilience as introduced by Zaccai is discussed and
      investigated using molecular dynamics simulation on camphor-bound cytochrome
      P450. The resilience of hydrophilic residues is found to be more strongly
      affected by hydration than that of hydrophobic counterparts. The hydration
      induced softening of protein propagates from the surface into the dry core.
      Moreover, buried hydrophilic residues behave more like those exposed on the
      protein surface, and are different from their hydrophobic counterparts. 

PMID- 23852577
TI  - Bending stiffness of biological membranes: what can be measured by neutron spin
      echo?
AB  - Large vesicles obtained by the extrusion method represent adequate membrane
      models to probe membrane dynamics with neutron radiation. Particularly, the shape
      fluctuations around the spherical average topology can be recorded by neutron
      spin echo (NSE). In this paper we report on the applicable theories describing
      the scattering contributions from bending-dominated shape fluctuations in diluted
      vesicle dispersions, with a focus on the relative relevance of the master
      translational mode with respect to the internal fluctuations. Different vesicle
      systems, including bilayer and non-bilayer membranes, have been scrutinized. We
      describe the practical ranges where the exact theory of bending fluctuations is
      applicable to obtain the values of the bending modulus from experiments, and we
      discuss about the possible internal modes that could be alternatively
      contributing to shape fluctuations. 

PMID- 23852578
TI  - Change of dynamics of raft-model membrane induced by amyloid-beta protein
      binding.
AB  - While the steady-state existence in the size and shape of liquid-ordered
      microdomains in cell membranes, the so-called "lipid rafts", still remain the
      subject of debate, glycosphingolipid-cholesterol rich regions in plasma membranes
      have been considered to have a function as platforms for signaling and sorting.
      In addition, recent spectroscopic studies show that the interaction between
      monosialoganglioside and amyloid beta (Abeta protein promotes the transition of
      Abeta from the native structure to the cross-beta fold in amyloid aggregates.
      However, there is few evidence on the dynamics of "lipid rafts" membranes. As the
      neutron spin-echo (NSE) technique is well known to detect directly slow dynamics
      of membrane systems in situ, by the combination of NSE and small-angle X-ray
      scattering we have studied the effect of the interaction between raft-model
      membrane and amyloid Abeta proteins on the structure and dynamics of a large uni
      lamellar vesicle (LUV) consisting of monosialoganglioside-cholesterol
      phospholipid ternary mixtures as a model of lipid-raft membrane. We have found
      that the interaction between the Abeta proteins and the model membrane at the
      liquid crystal phase significantly suppresses a bending-diffusion motion with a
      minor effect on the LUV structure. The present results would suggest a
      possibility of non-receptor-mediated disorder in signaling through a modulation
      of a membrane dynamics induced by the association of amyloidogenic peptides on a
      plasma membrane. 

PMID- 23852579
TI  - Neutrons for rafts, rafts for neutrons.
AB  - The determination of the structure of membrane rafts is a challenging issue in
      biology. The selection of membrane components both in the longitudinal and
      transverse directions plays a major role as it determines the creation of stable
      or tunable platforms that host interactions with components of the outer
      environment. We focus here on the possibility to apply neutron scattering to the
      study of raft mimics. With this aim, we realized two extreme experimental models
      for the same complex membrane system (phospholipid : cholesterol : ganglioside
      GM1), involving two of the characteristic components of glycolipid-enriched
      rafts. One consists of a thick stack of tightly packed membranes, mixed and
      symmetric in composition, deposited on a silicon wafer and analyzed by neutron
      diffraction. The other consists of a free floating individual membrane, mixed and
      asymmetric in composition in the two layers, studied by neutron reflection. We
      present here results on the ganglioside-cholesterol coupling. Ganglioside GM1 is
      found to force the redistribution of cholesterol between the two layers of the
      model membranes. This causes cholesterol exclusion from compositionally symmetric
      ganglioside-containing membranes, or, alternatively, asymmetric cholesterol
      enrichment in raft-mimics, where gangliosides reside into the opposite layer. 

PMID- 23852580
TI  - Small angle neutron scattering for the study of solubilised membrane proteins.
AB  - Small angle neutron scattering (SANS) is a powerful technique for investigating
      association states and conformational changes of biological macromolecules in
      solution. SANS is of particular interest for the study of the multi-component
      systems, as membrane protein complexes, for which in vitro characterisation and
      structure determination are often difficult. This article details the important
      physical properties of surfactants in view of small angle neutron scattering
      studies and the interest to deuterate membrane proteins for contrast variation
      studies. We present strategies for the production of deuterated membrane proteins
      and methods for quality control. We then review some studies on membrane
      proteins, and focus on the strategies to overcome the intrinsic difficulty to
      eliminate homogeneously the detergent or surfactant signal for solubilised
      membrane proteins, or that of lipids for membrane proteins inserted in liposomes.

PMID- 23852581
TI  - Pharmacological validation of a refined burrowing paradigm for prediction of
      analgesic efficacy in a rat model of sub-chronic knee joint inflammation.
AB  - BACKGROUND: Burrowing is an evolutionarily conserved behaviour in rodents. This
      study validates a refined burrowing paradigm (requiring a reduced number of
      animals) in a rat model of sub-chronic knee joint inflammation and evaluates its
      sensitivity and specificity for analgesic drugs. METHODS: Knee joint inflammation
      in rats was induced by intra-articular injection with complete Freund's adjuvant
      (CFA). Burrowing performance was assessed at baseline without study drugs, and in
      CFA-naive and CFA-injected animals following administration of the analgesic
      drugs naproxen, pregabalin and morphine, each at three doses, or corresponding
      vehicle (nine rats per dose group). The specificity of the model was evaluated by
      also testing the anxiogenic drug yohimbine, the stimulant drug dexamphetamine and
      the anxiolytic drug chlordiazepoxide in CFA-naive and CFA-injected animals.
      Percentage maximum possible effect (%MPE) was determined by relating the
      difference between post-CFA and baseline burrowing performance in each drug dose
      group to that in the vehicle group in each experiment. RESULTS: Burrowing
      performance in the vehicle groups was decreased by 39.0-59.8% in CFA-injected
      animals compared with CFA-naive animals. CFA-induced reductions in burrowing
      performance were reversed by each of the three analgesic drugs tested. The
      highest %MPE was 75.2% with naproxen 50 mg/kg, 80.9% with pregabalin 10 mg/kg and
      77.0% with morphine 1 mg/kg (all p < 0.05 vs. control). CFA-induced reductions in
      burrowing performance were not reversed by yohimbine, dexamphetamine or
      chlordiazepoxide. CONCLUSIONS: This study provides pharmacological validation of
      a refined burrowing paradigm for analgesic efficacy that exhibits good predictive
      validity, with high sensitivity and specificity.

PMID- 23852583
TI  - Adaptive responses of TRPC1 and TRPC3 during skeletal muscle atrophy and
      regrowth.
AB  - INTRODUCTION: We assessed the time-dependent changes of transient receptor
      potential canonical type 1 (TRPC1) and TRPC3 expression and localization
      associated with muscle atrophy and regrowth in vivo. METHODS: Mice were subjected
      to hindlimb unloading for 7 or 14 days (7U, 14U) followed by 3, 7, or 14 days of
      reloading (3R, 7R, 14R). RESULTS: Soleus muscle mass and tetanic force were
      reduced significantly at 7U and 14U and recovered by 14R. Recovery of muscle
      fiber cross-sectional area was observed by 28R. TRPC1 mRNA was unaltered during
      the unloading-reloading period. However, protein expression remained depressed
      through 14R. Decreased localization of TRPC1 to the sarcolemma was observed.
      TRPC3 mRNA and protein expression levels were decreased significantly during the
      early phase of reloading. CONCLUSIONS: Given the known role of these channels in
      muscle development, changes observed in TRPC1 and TRPC3 may relate closely to
      muscle atrophy and remodeling processes.

PMID- 23852582
TI  - RNA-based tools for nuclear reprogramming and lineage-conversion: towards
      clinical applications.
AB  - The therapeutic potential of induced pluripotent stem cells (iPSCs) is well
      established. Safety concerns remain, however, and these have driven considerable
      efforts aimed at avoiding host genome alteration during the reprogramming
      process. At present, the tools used to generate human iPSCs include (1) DNA-based
      integrative and non-integrative methods and (2) DNA-free reprogramming
      technologies, including RNA-based approaches. Because of their combined
      efficiency and safety characteristics, RNA-based methods have emerged as the most
      promising tool for future iPSC-based regenerative medicine applications. Here, I
      will discuss novel recent advances in reprogramming technology, especially those
      utilizing the Sendai virus (SeV) and synthetic modified mRNA. In the future,
      these technologies may find utility in iPSC reprogramming for cellular lineage
      conversion, and its subsequent use in cell-based therapies. 

PMID- 23852584
TI  - Predictive model for disinfection by-product in Alexandria drinking water,
      northern west of Egypt.
AB  - Chlorine has been utilized in the early stages of water treatment processes as
      disinfectant. Disinfection for drinking water reduces the risk of pathogenic
      infection but may pose a chemical threat to human health due to disinfection
      residues and their by-products (DBP) when the organic and inorganic precursors
      are present in water. In the last two decades, many modeling attempts have been
      made to predict the occurrence of DBP in drinking water. Models have been
      developed based on data generated in laboratory-scale and field-scale
      investigations. The objective of this paper is to develop a predictive model for
      DBP formation in the Alexandria governorate located at the northern west of Egypt
      based on field-scale investigations as well as laboratory-controlled
      experimentations. The present study showed that the correlation coefficient
      between trihalomethanes (THM) predicted and THM measured was R (2)=0.88 and the
      minimum deviation percentage between THM predicted and THM measured was 0.8 %,
      the maximum deviation percentage was 89.3 %, and the average deviation was 17.8
      %, while the correlation coefficient between dichloroacetic acid (DCAA) predicted
      and DCAA measured was R (2)=0.98 and the minimum deviation percentage between
      DCAA predicted and DCAA measured was 1.3 %, the maximum deviation percentage was
      47.2 %, and the average deviation was 16.6 %. In addition, the correlation
      coefficient between trichloroacetic acid (TCAA) predicted and TCAA measured was R
      (2)=0.98 and the minimum deviation percentage between TCAA predicted and TCAA
      measured was 4.9 %, the maximum deviation percentage was 43.0 %, and the average
      deviation was 16.0 %.

PMID- 23852585
TI  - Concentration levels and congener profiles of polychlorinated biphenyls,
      pentachlorobenzene, and hexachlorobenzene in commercial pigments.
AB  - The concentration levels and congener profiles of polychlorinated biphenyls
      (PCBs), pentachlorobenzene (PeCBz), and hexachlorobenzene (HxCBz) were assessed
      in commercially available organic pigments. Among the azo-type pigments tested,
      PCB-11, which is synthesized from 3,3'-dichlorobendizine, and PCB-52, which is
      synthesized from 2,2',5,5'-tetrachlorobendizine, were the major congeners
      detected. It is speculated that these were byproducts of chlorobendizine, which
      has a very similar structure. The total PCB concentrations in this type of
      pigment ranged from 0.0070 to 740 mg/kg. Among the phthalocyanine-type pigments,
      highly chlorinated PCBs, mainly composed of PCB-209, PeCBz, and HxCBz were
      detected. Their concentration levels ranged from 0.011 to 2.5 mg/kg, 0.0035 to
      8.4 mg/kg, and 0.027 to 75 mg/kg, respectively. It is suggested that PeCBz and
      HxCBz were formed as byproducts and converted into PCBs at the time of
      synthesizing the phthalocyanine green. For the polycyclic-type pigments that were
      assessed, a distinctive PCB congener profile was detected that suggested an
      impact of their raw materials and the organic solvent used in the pigment
      synthesis. PCB pollution from PCB-11, PCB-52, and PCB-209 pigments is of
      particular concern; therefore, the monthly variations in atmospheric
      concentrations of these pollutants were measured in an urban area (Sapporo city)
      and an industrial area (Muroran city). The study detected a certain level of PCB
      11, which is not included in PCB technical mixtures, and revealed continuing PCB
      pollution originating from pigments in the ambient air. 

PMID- 23852586
TI  - Polymorphisms in DNA repair genes, recreational physical activity and breast
      cancer risk.
AB  - The mechanisms driving the inverse association between recreational physical
      activity (RPA) and breast cancer risk are complex. While exercise is associated
      with increased reactive oxygen species production it may also improve damage
      repair systems, particularly those that operate on single-strand breaks including
      base excision repair (BER), nucleotide excision repair (NER) and mismatch repair
      (MMR). Of these repair pathways, the role of MMR in breast carcinogenesis is
      least investigated. Polymorphisms in MMR or other DNA repair gene variants may
      modify the association between RPA and breast cancer incidence. We investigated
      the individual and joint effects of variants in three MMR pathway genes (MSH3,
      MLH1 and MSH2) on breast cancer occurrence using resources from the Long Island
      Breast Cancer Study Project. We additionally characterized interactions between
      RPA and genetic polymorphisms in MMR, BER and NER pathways. We found
      statistically significant multiplicative interactions (p < 0.05) between MSH2 and
      MLH1, as well as between postmenopausal RPA and four variants in DNA repair (XPC
      Ala499Val, XPF-Arg415Gln, XPG-Asp1104His and MLH1-lle219Val). Significant risk
      reductions were observed among highly active women with the common genotype for
      XPC (OR = 0.54; 95% CI, 0.36-0.81) and XPF (OR = 0.62; 95% CI, 0.44-0.87), as
      well as among active women who carried at least one variant allele in XPG (OR =
      0.46; 95% CI, 0.29-0.77) and MLH1 (OR = 0.46; 95% CI, 0.30-0.71). Our data show
      that women with minor alleles in both MSH2 and MLH1 could be at increased breast
      cancer risk. RPA may be modified by genes in the DNA repair pathway, and merit
      further investigation. 

PMID- 23852587
TI  - Increased carboxyhemoglobin in adult falciparum malaria is associated with
      disease severity and mortality.
AB  - Heme oxygenase 1 expression is increased in pediatric patients with malaria. The
      carboxyhemoglobin level (a measure of heme oxygenase 1 activity) has not been
      assessed in adult patients with malaria. Results of pulse co-oximetry revealed
      that the mean carboxyhemoglobin level was elevated in 29 Indonesian adults with
      severe falciparum malaria (10%; 95% confidence interval [CI], 8%-13%) and in 20
      with severe sepsis (8%; 95% CI, 5%-12%), compared with the mean levels in 32
      patients with moderately severe malaria (7%; 95% CI, 5%-8%) and 36 controls
      (3.6%; 95% CI, 3%-5%; P < .001). An increased carboxyhemoglobin level was
      associated with an increased odds of death among patients with severe malaria
      (odds ratio, 1.2 per percentage point increase; 95% CI, 1.02-1.5). While also
      associated with severity and fatality, methemoglobin was only modestly increased
      in patients with severe malaria. Increased carboxyhemoglobin levels during severe
      malaria and sepsis may exacerbate organ dysfunction by reducing oxygen carriage
      and cautions against the use of adjunctive CO therapy, which was proposed on the
      basis of mouse models. 

PMID- 23852588
TI  - Geographic and temporal trends in antimicrobial nonsusceptibility in
      Streptococcus pneumoniae in the post-vaccine era in the United States.
AB  - BACKGROUND: We examined whether observed increases in antibiotic nonsusceptible
      nonvaccine serotypes after introduction of pneumococcal conjugate vaccine in the
      United States in 2000 were driven primarily by vaccine or antibiotic use.
      METHODS:  Using active surveillance data, we evaluated geographic and temporal
      differences in serotype distribution and within-serotype differences during 2000
      2009. We compared nonsusceptibility to penicillin and erythromycin by geography
      after standardizing differences across time, place, and serotype by regressing
      standardized versus crude proportions. A regression slope (RS) approaching zero
      indicates greater importance of the standardizing factor. RESULTS:  Through 2000
      2006, geographic differences in nonsusceptibility were better explained by within
      serotype prevalence of nonsusceptibility (RS 0.32, 95% confidence interval [CI],
      .08-.55 for penicillin) than by geographic differences in serotype distribution
      (RS 0.71, 95% CI, .44-.97). From 2007-2009, serotype distribution differences
      became more important for penicillin (within-serotype RS 0.52, 95% CI, .11-.93;
      serotype distribution RS 0.57, 95% CI, .14-1.0). CONCLUSIONS:  Differential
      nonsusceptibility, within individual serotypes, accounts for most geographic
      variation in nonsusceptibility, suggesting selective pressure from antibiotic
      use, rather than differences in serotype distribution, mainly determines
      nonsusceptibility patterns. Recent trends suggest geographic differences in
      serotype distribution may be affecting the prevalence of nonsusceptibility,
      possibly due to decreases in the number of nonsusceptible serotypes.

PMID- 23852589
TI  - Influence of arthroscopic lateral release on functional recovery in adolescents
      with recurrent patellar dislocation.
AB  - INTRODUCTION: The aim of this study is to prove the influence of the arthroscopic
      lateral release on functional recovery in adolescents with recurrent lateral
      dislocation of patella. MATERIALS AND METHODS: From 2006 to 2009, arthroscopic
      release of the lateral retinaculum was done on 27 adolescent patients (24 women,
      3 men) and 33 knees (in 6 patients on both knees). All of them were active in
      different sports. The severity of patellar subluxation and dislocation was
      analysed on X-ray; the Q angle, congruence angle, sulcus angle, patellofemoral
      angle and height ratio were measured. Functional scores (Lysholm, Kujala, Tegner)
      were measured preoperatively and postoperatively. The average duration of
      clinical and X-ray follow-up was 4.5 years (range 3-6 years). RESULTS: The mean
      age of the patients was 14.56 years (range 11-18 years). There was an average of
      4.16 dislocations (range 2-28 dislocations) before surgery. The mean Lysholm
      score improved from 64 to 95 (p = 0.0002), and the mean Kujala score improved
      from 66 to 94 (p < 0.0001). Congruence angle and lateral patellofemoral angle
      improved but without any significant differences. CONCLUSION: Arthroscopic
      lateral release successfully treats recurrent patellar dislocations in
      adolescents, influences functional recovery and improves knee function.

PMID- 23852590
TI  - Clinical features and surgical outcomes of lumbar spinal stenosis in patients
      aged 80 years or older: a multi-center retrospective study.
AB  - INTRODUCTION: With increased aging of the population, spine surgeons have more
      opportunity to treat elderly patients for lumbar spinal stenosis (LSS). The
      purpose of this study was to clarify the clinical features and surgical outcomes
      for LSS in the elderly aged 80 years or older. MATERIALS AND METHODS: We
      retrospectively reviewed 702 consecutive patients with LSS who underwent
      decompression surgery without fusion between 2006 and 2010. Patients with other
      conditions that could affect functional status were excluded from this study. Of
      the remaining 304 patients, 241 with LSS whose condition could be evaluated 6
      months at least after surgery were analyzed. The mean follow-up period was 14.4
      months (range 6-60 months). There were 144 males and 97 females aged 45-93 years
      old (average: 72.2 years old). Patients were divided into two age groups: 80
      years or older (Group A, 46 patients) and under 80 years of age (Group B, 195
      patients). We evaluated differences in the clinical features and surgical
      outcomes between the two groups. RESULTS: There were no significant differences
      in surgical levels, the number of operation levels, operation times, or the
      amount of intraoperative bleeding between Groups A and B. The percentages of
      patients with comorbidities were 73.9 % in Group A and 60.0 % in Group B, which
      were not significantly different. There were no significant differences in
      Japanese Orthopaedic Association scores preoperatively, 6 months postoperatively,
      and at the final follow-up between the two groups. Furthermore, recovery ratios 6
      months postoperatively and at final follow-up were similar between the two
      groups. The percentages of patients with postoperative complications were 19.6 %
      in Group A and 13.3 % in Group B, which were not significantly different.
      CONCLUSIONS: This multi-center retrospective study demonstrated that the benefits
      and risks of decompression surgery for LSS were similar between patients aged
      over 80 years and those under 80 years. Therefore, decompression surgery is a
      reasonable treatment even for elderly patients aged over 80 years.

PMID- 23852591
TI  - Glenoid morphology affects the incidence of radiolucent lines around cemented
      pegged polyethylene glenoid components.
AB  - PURPOSE: Radiolucent lines (RLL) are frequent findings around cemented all
      polyethylene glenoid implants. The present study evaluates the frequency, extend
      and the clinical impact of RLL around a cemented two-pegged glenoid implant with
      special focus on the influence of preoperative glenoid morphology. Our hypothesis
      was that glenoid morphology does not affect clinical outcome and RLL in the
      investigated setting. METHODS: Between 2003 and 2008, a total of 113 cases of
      total shoulder arthroplasties (Affinis, Mathys Ltd Bettlach, Switzerland) were
      performed in three surgical centres using a pegged cemented polyethylene glenoid
      component. A total of 90 cases could be evaluated clinically and
      radiographically. Clinical outcome was analysed using the constant score (CS) and
      range of motion assessment. Radiographic evaluation was performed in true
      anterior-posterior and axial views with special focus on loosening and RLL.
      Further, preoperative glenoid morphology was documented and its correlation to
      radiolucent lines and clinical outcomes was evaluated. RESULTS: At a mean of 58.8
      (range 31.2-92.5)-month follow-up the CS improved from 21.5 points preoperatively
      to 62.3 points postoperatively. Radiolucent lines were found in 76.6 % of cases.
      If present, RLL were located at the backside of the implant (74.4 %) in the
      majority of the cases not around the pegs (10 %). There was no significant
      correlation between RLL and clinical outcome or follow-up time. The amount and
      extend of RLL were correlated to glenoid morphology with significantly higher
      values for glenoid types B2 and C according to Walch in comparison to glenoid
      types A1, A2 and B1. CONCLUSIONS: RLL did not affect clinical outcome and did not
      correlate with the follow-up time. Patients with glenoid morphology types B2 and
      C showed significantly worse radiographic results. LEVEL OF EVIDENCE: Level IV
      case series study.

PMID- 23852592
TI  - Assessing beta-amyloid-induced NLRP3 inflammasome activation in primary
      microglia.
AB  - Senile plaques are an important histological hallmark of Alzheimer's disease.
      They mainly consist of the fibrillar peptide beta-amyloid (Abeta) and are
      surrounded by activated microglia and astrocytes. Microglia in the vicinity of
      senile plaques express high levels of proinflammatory cytokines and neurotoxic
      substances, which are believed to influence disease progression. One important
      cytokine in Alzheimer's disease is IL-1beta. Stimulation of cultured primary
      microglia by synthetic fibrillar Abeta causes the release of IL-1beta via
      activation of the NLRP3 inflammasome.Here we provide protocols for the
      preparation of primary microglial cultures and synthetic oligomeric and fibrillar
      forms of Abeta.

PMID- 23852593
TI  - Activating the NLRP3 inflammasome using the amyloidogenic peptide IAPP.
AB  - In addition to several other extracellular substances, phagocytosis of amyloid
      forming peptides can perturb cellular homeostasis, leading to activation of the
      cytoplasmic innate immune receptor NLRP3. Once triggered, NLRP3 forms an
      inflammasome complex that ultimately cleaves pro-IL-1beta and pro-IL-18 into
      their mature, secreted forms. Here we describe a protocol by which one type of
      amyloidogenic peptide, islet amyloid polypeptide (IAPP, otherwise known as
      amylin) can be prepared and used to stimulate myeloid cells in vitro to engage
      the NLRP3 inflammasome. Methods for measuring the ensuing inflammasome activation
      are also described. Although initially soluble, IAPP monomers rapidly aggregate
      in solution to form oligomers and subsequently insoluble amyloid fibrils. More
      work is required to examine how this transition influences inflammasome
      activation for different types of amyloid. The course of amyloid formation and
      corresponding inflammatory capacity of these pre-fibrillar species following
      uptake also requires further examination, and we hope that our protocols are
      useful in these endeavors. While these protocols are restricted to examination of
      synthetic IAPP, isolation of IAPP aggregates from human and transgenic mouse
      pancreas will be required to definitively determine the proinflammatory effects
      of endogenous IAPP oligomers and fibrils.

PMID- 23852594
TI  - Assessment and quantification of crystal-induced lysosomal damage.
AB  - Lysosomes are organelles that degrade endocytosed, phagocytosed, or
      autophagocytosed materials. Lysosomal degradation of engulfed material is a
      highly controlled mechanism, which is vital in the control of infection,
      recycling of cellular organelles, and the breakdown of larger material. Following
      ingestion, lysosomes acidify and mature, leading to the activation of a range of
      proteolytic enzymes. Lysosomes are considered stable organelles that separate
      their highly hydrolytic enzymes from the cytosol to prevent digestion of self
      molecules and host cell damage. Some substances, mostly of a particulate or
      aggregated nature, are able to damage lysosomes. Lysosomal damage and rupture,
      with subsequent release of lysosomal content into the cytosol can have dramatic
      consequences for the cell, such as the induction of cell death or activation of
      the NLRP3 inflammasome. In this chapter, we provide methods for the induction,
      assessment, and quantification of lysosomal damage by flow cytometry and confocal
      microscopy.

PMID- 23852595
TI  - Assessment of inflammasome activation in primary human immune cells.
AB  - Inflammasomes are central regulators of inflammation, responsible for cleavage of
      the inactive pro--inflammatory cytokines IL-1beta and IL-18 into their
      biologically active counterparts. Several regulatory stages within the pathways
      responsible for the production of these cytokines have been identified. In this
      chapter, methods are described for assessing the degree of activity of these
      regulatory stages, which include mRNA transcription, caspase-1 activation, and
      secretion of the bioactive proteins.

PMID- 23852596
TI  - NLRP3 inflammasome activation and cytotoxicity induced by particulate adjuvants.
AB  - The ability of particulate materials to provoke inflammatory immune responses has
      been well documented. In the case of endogenous and environmental particulates,
      these effects can often lead to pathological disorders. In contrast, particulate
      adjuvants incorporated into vaccines promote immune responses, which in turn
      provide efficient protection against infectious diseases. In recent years,
      studies have revealed that the NLRP3 inflammasome plays a key role in particulate
      driven inflammation and its associated cytotoxicity. Hence, this chapter covers
      protocols useful to (1) assess NLRP3 inflammasome activation triggered by
      particulate adjuvants or materials in mouse bone marrow-derived dendritic cell
      (BMDCs) differentiated cultures, and (2) measure particle-induced cytotoxicity.
      More specifically, protocols are described for the preparation and
      differentiation of BMDCs, their priming and stimulation using particulate NLRP3
      agonists such as monosodium urate monohydrate (MSU) and the vaccine adjuvant
      alum. We then detail protocols to assess particulate-driven cytotoxicity via flow
      cytometry using annexin V-propidium iodide (PI) and novel dye LIVE/DEAD((r)) aqua
      stain. General considerations are provided that warn against the use of endotoxin
      contaminated particles and emphasize the use of experimental controls.
      Suggestions are also outlined for further assessment of the immunomodulatory
      effects of particulate materials in vivo using the mouse peritonitis model.

PMID- 23852597
TI  - Measuring inflammasome activation in response to bacterial infection.
AB  - Inflammasomes are multi-protein signaling platforms assembled in response to
      viral and bacterial pathogens as well as endogenous danger signals. Inflammasomes
      serve as activation platforms for the mammalian cysteine protease caspase-1, a
      central mediator of innate immunity. The hallmarks of inflammasome activation are
      the processing of caspase-1, the maturation and release of interleukin-1beta (IL
      1beta) and the induction of pyroptosis, a lytic inflammatory cell death. This
      protocol describes methods for studying inflammasome activation in response to
      bacterial pathogens in bone-marrow derived murine macrophages (BMDMs). In
      particular, we outline the protocols to measure cytokine maturation by ELISA and
      pyroptosis by the release of Lactate Dehydrogenase (LDH). In addition, we
      describe methods to visualize endogenous ASC specks or foci in infected cells and
      to study the release of processed caspase-1, caspase-11 and mature cytokines into
      the cell supernatant by Western blotting. General considerations are discussed to
      design and optimize the infection protocol for the study of inflammasome
      activation by other bacterial pathogens.

PMID- 23852598
TI  - Detection of pyroptosis by measuring released lactate dehydrogenase activity.
AB  - Pyroptosis is a form of programmed, inflammatory cell death that is dependent on
      the activation of a cysteine protease caspase-1. Following caspase-1 activation
      via inflammasomes (including NLRP3, NLRC4, Nlrp1b, and AIM2), cells lose membrane
      integrity and lyse, releasing lactate dehydrogenase (LDH) that is normally
      maintained within the cell cytosol. Thus, pyroptosis is distinct from apoptosis,
      which results in cellular contents being enclosed within membrane blebs during
      cellular demise. LDH is only released from apoptotic blebs after secondary
      necrosis occurs. Pyroptosis is distinct from necrosis in that it requires the
      activity of caspase-1. In this chapter, we describe enzymatic assays for the
      detection of LDH released by pyroptotic cells using a commercially available kit,
      as well as a simple and cost-effective method adapted from Decker et al. (J
      Immunol Methods 115:61-69, 1988).

PMID- 23852599
TI  - ASC speck formation as a readout for inflammasome activation.
AB  - All inflammasomes require the adapter protein apoptosis associated speck-like
      protein containing a CARD (ASC) for the activation of caspase-1. After
      inflammasome activation, ASC assembles into a large protein complex, which is
      termed "speck". ASC specks can be observed as they reach a size of around 1 MUm
      and in most cells only one speck forms upon inflammasome activation. Hence, ASC
      speck formation can be used as a simple upstream readout for inflammasome
      activation. Here, we describe a method for analyzing inflammasome activation by
      ASC speck visualization. First, we describe the generation of a clonal
      inflammasome reporter macrophage cell line overexpressing fluorescently tagged
      ASC. We then discuss stimulation conditions and the microscopic evaluation of ASC
      speck formation.

PMID- 23852600
TI  - Immunoblotting for active caspase-1.
AB  - Immunoblotting for caspase-1 is the gold-standard method of detecting
      inflammasome activation. In contrast to IL-1beta-based readouts, it can be used
      in an experimental setup independent of de novo gene expression. Here, we present
      protocols for the preparation and precipitation of supernatant samples containing
      activated caspase-1 as well as protocols for polyacrylamide gel electrophoresis
      (PAGE) and protein immunoblotting. 

PMID- 23852601
TI  - Inflammasome activation and inhibition in primary murine bone marrow-derived
      cells, and assays for IL-1alpha, IL-1beta, and caspase-1.
AB  - Through its ability to control the proteolytic maturation and secretion of
      interleukin-1 family cytokines, the inflammasome occupies a central role in the
      activation of inflammation and also influences the shaping of adaptive immunity.
      Since it affects a multitude of different immune responses from autoinflammatory
      diseases to host defense, vaccine efficacy, and even cancer, it has become of
      interest to many researchers. Here, we describe a straightforward method for
      inflammasome assays in primary murine bone marrow--derived myeloid cells. The
      protocol encompasses cell handling, inflammasome activation and inhibition, as
      well as the detection of IL-1beta, caspase-1, and IL-1alpha by ELISA and Western
      blot.

PMID- 23852602
TI  - Reconstituting the NLRP1 inflammasome in vitro.
AB  - Nucleotide-binding domain leucine-rich-repeat containing receptors; NOD-Like
      Receptors (NLRs) were originally described as microbial sensors involved in host
      defense against pathogens that comprise an important component of the innate
      immune system. Recently, their cellular functions have expanded beyond classical
      pathogen detection, to danger sensors that may contribute to the pathophysiology
      of a wide range of inflammation-driven human illnesses such as metabolic diseases
      (atherosclerosis, obesity, type 2 diabetes, gout, age-related macular
      degeneration) and neurological disorders (Alzheimer's disease). Pathogen
      stimulated NLRs such as NLR family Pyrin domain-containing protein 1 (NLRP1)
      assemble into molecular platforms called "inflammasomes" to activate inflammatory
      protease caspase-1, which processes pro-IL-1beta and pro-IL-18 into active
      cytokines. We describe methods for reconstituting the human NLRP1 inflammasome in
      vitro. Protocols are provided for: (a) expression and purification of
      inflammasome core components (NLRP1 and pro-caspase-1 proteins) using the
      baculovirus/insect cell expression system, and (b) functional monitoring of NLRP1
      mediated caspase-1 activation in response to NLRP1 ligand muramyl dipeptide (MDP)
      and ATP.

PMID- 23852603
TI  - Assessing ATP binding and hydrolysis by NLR proteins.
AB  - Nucleotide-binding and leucine rich repeat domain-containing proteins (NLRs) are
      central to the formation of many inflammasome complexes. Several inflammasome
      forming NLR proteins are known to be ATPases, but the nucleotide binding
      specificity of many remains to be characterized. The oligomerization of NLR
      proteins and assembly of inflammasomes require the ATP (or other nucleotide)
      binding activity of the NLR proteins. Quantitative and qualitative studies of the
      nucleotide binding properties of these proteins are useful tools in studying the
      regulation of inflammasome activity, and are outlined in this Chapter. 

PMID- 23852604
TI  - Blue native polyacrylamide gel electrophoresis to monitor inflammasome assembly
      and composition.
AB  - Inflammasomes are large cytosolic multi-protein complexes that form in response
      to infection and other stimuli, and play an important role in the innate immune
      response. Traditional methods for assaying inflammasome activation have relied on
      detection of autoproteolysis of the cysteine protease caspase-1, or proteolytic
      processing of its substrate, the inflammatory cytokine IL-1beta. These
      measurements report on the final output of inflammasome activation, but do not
      assess inflammasome assembly and composition. Here we describe the application of
      blue native gel electrophoresis as a tool for investigating stimulus-dependent
      inflammasome assembly and for identification of individual components within the
      multi-protein complex.

PMID- 23852605
TI  - Analysis of microbiota alterations in inflammasome-deficient mice.
AB  - Inflammasomes have emerged as central regulators of intestinal infection,
      immunity, and inflammation. Inflammasome activity mediates intestinal epithelial
      integrity, antimicrobial responses, and initiates inflammation through generation
      of the cytokines interleukin (IL-)1 and IL-18. Recent studies have identified an
      additional layer of inflammasome function in the intestine, namely, the control
      of intestinal microflora composition. Inflammasome-deficient mice show an
      aberrant microbial community which is dominantly transmissible to healthy mice.
      This dysbiosis in inflammasome-deficient mice has a profound impact on their
      physiology and pathophysiology, both locally in the intestine and systemically.
      Therefore, it is essential to consider the influence of the composition of
      microbial communities on experiments performed with inflammasome-deficient and
      other innate molecule-deficient mice, and to conduct experiments to control for
      potential dominant effects of the microflora on host responses. In this chapter,
      we provide experimental procedures to monitor inflammasome-mediated modifications
      of the intestinal microflora composition in mice and to test the resultant
      functional consequences of these changes in microbial communities and their
      transmission to cohoused mice.

PMID- 23852607
TI  - In vivo evaluation of neutrophil recruitment in response to sterile particulates.
AB  - Sterile particulates such as monosodium urate crystals induce inflammasome
      activation resulting in activation of caspase-1, secretion of IL-1alpha, and
      processing of IL-1beta. Local production and activation of IL-1 leads to
      neutrophil recruitment in vivo. Here we describe two quick and simple methods for
      the evaluation of neutrophil recruitment in the peritoneal cavity and skin in
      response to sterile particulates, which are dependent on IL-1 receptor signaling.

PMID- 23852606
TI  - Quantification of adipose tissue leukocytosis in obesity.
AB  - The infiltration of immune cell subsets in adipose tissue termed "adipose tissue
      leukocytosis" is a critical event in the development of chronic inflammation and
      obesity-associated comorbidities. Given that a significant proportion of cells in
      adipose tissue of obese patients are of hematopoietic lineage, the distinct
      adipose depots represent an uncharacterized immunological organ that can impact
      metabolic functions. Here, we describe approaches to characterize and isolate
      leukocytes from the complex adipose tissue microenvironment, to aid mechanistic
      studies to better understand the role of specific pattern recognition receptors
      (PRRs) such as inflammasomes in adipose-immune cross talk. 

PMID- 23852608
TI  - Postmortem analyses of drugs in pericardial fluid and bone marrow aspirate.
AB  - In forensic toxicology, bone marrow is often used when adequate blood samples are
      not available; however, pericardial fluid (PCF) has been poorly investigated. The
      present study comprehensively reviewed the toxicological data of blood, PCF and
      bone marrow aspirate (BMA) in forensic autopsy cases to investigate drug
      distribution. Analysis using automated gas chromatography/mass spectrometry (GC
      MS) following solid/liquid phase extraction detected 36 drugs in 218 cases (8.0%
      among 2,724 cases examined). Drug distribution varied by drug as well as partly
      by case even when taken as a mixture. Most of the drugs showed overall similar
      distributions in right heart blood, PCF and BMA with some exceptions, however,
      several drugs, including phenothiazine derivatives and antidepressants, were
      detected at ~1.5 times (1.2-2.0) higher levels in BMA than in right heart blood,
      but PCF levels were mostly equivalent to blood levels. Midazolam, propofol and
      thiamylal (intravenous anesthetics) were detected at a substantially lower
      concentration in PCF than in blood or BMA. These observations suggest that PCF
      and BMA are useful materials to be included in the forensic toxicological routine
      when blood samples are not available, as well as to investigate pharmaco
      /toxicokinetics and postmortem redistribution.

PMID- 23852609
TI  - Stratified meta-analysis of intermittent pneumatic compression of the lower limbs
      to prevent venous thromboembolism in hospitalized patients.
AB  - BACKGROUND: Optimal thromboprophylaxis for patients at risk of bleeding remains
      uncertain. This meta-analysis assessed whether intermittent pneumatic compression
      (IPC) of the lower limbs was effective in reducing venous thromboembolism and
      whether combining pharmacological thromboprophylaxis with IPC would enhance its
      effectiveness. METHODS AND RESULTS: Two reviewers searched MEDLINE, EMBASE, and
      the Cochrane controlled trial register (1966-February 2013) for randomized,
      controlled trials and assessed the outcomes and quality of the trials
      independently. Trials comparing IPC with pharmacological thromboprophylaxis,
      thromboembolic deterrent stockings, no prophylaxis, and a combination of IPC and
      pharmacological thromboprophylaxis were considered. Trials that used IPC <24
      hours or compared different types of IPC were excluded. A total of 16 164
      hospitalized patients from 70 trials met the inclusion criteria and were
      subjected to meta-analysis. IPC was more effective than no IPC prophylaxis in
      reducing deep vein thrombosis (7.3% versus 16.7%; absolute risk reduction, 9.4%;
      95% confidence interval [CI], 7.9-10.9; relative risk, 0.43; 95% CI, 0.36-0.52;
      P<0.01; I(2)=34%) and pulmonary embolism (1.2% versus 2.8%; absolute risk
      reduction, 1.6%; 95% CI, 0.9-2.3; relative risk, 0.48; 95% CI, 0.33-0.69; P<0.01;
      I(2)=0%). IPC was also more effective than thromboembolic deterrent stockings in
      reducing deep vein thrombosis and appeared to be as effective as pharmacological
      thromboprophylaxis but with a reduced risk of bleeding (relative risk, 0.41; 95%
      CI, 0.25-0.65; P<0.01; I(2)=0%). Adding pharmacological thromboprophylaxis to IPC
      further reduced the risk of deep vein thrombosis (relative risk, 0.54; 95% CI,
      0.32-0.91; P=0.02; I(2)=0%) compared with IPC alone. CONCLUSIONS: IPC was
      effective in reducing venous thromboembolism, and combining pharmacological
      thromboprophylaxis with IPC was more effective than using IPC alone.

PMID- 23852610
TI  - Elderly patients with acute coronary syndromes managed without revascularization:
      insights into the safety of long-term dual antiplatelet therapy with reduced-dose
      prasugrel versus standard-dose clopidogrel.
AB  - BACKGROUND: Dual antiplatelet therapy in older versus younger patients with acute
      coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended
      for younger, lower-body-weight patients and elderly patients with acute coronary
      syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d).
      METHODS AND RESULTS: A total of 9326 medically managed patients with acute
      coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal
      Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (<75
      years of age, n=7243; >=75 years of age, n=2083) were randomized to prasugrel (10
      mg/d; 5 mg/d for those >=75 or <75 years of age and <60 kg in weight) or
      clopidogrel (75 mg/d) plus aspirin for <=30 months. A total of 515 participants
      >=75 years of age (25% of total elderly population) had serial platelet
      reactivity unit measurements in a platelet-function substudy. Cumulative risks of
      the primary end point (cardiovascular death/myocardial infarction/stroke) and
      Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased
      progressively with age and were >=2-fold higher in older participants. Among
      those >=75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio,
      1.09; 95% confidence interval, 0.57-2.08) and the primary end point rates were
      similar with reduced-dose prasugrel and clopidogrel. Despite a correlation
      between lower 30-day on-treatment platelet reactivity unit values and lower
      weight only in the prasugrel group, there was a nonsignificant treatment-by
      weight interaction for platelet reactivity unit values among participants >=75
      years of age in the platelet-function substudy (P=0.06). No differences in weight
      were seen in all participants >=75 years of age with versus without TIMI
      major/minor bleeding in both treatment groups. CONCLUSIONS: Older age is
      associated with substantially increased long-term cardiovascular risk and
      bleeding among patients with medically managed acute coronary syndromes, with no
      differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared
      with clopidogrel in elderly patients. No significant interactions among weight,
      pharmacodynamic response, and bleeding risk were observed between reduced-dose
      prasugrel and clopidogrel in elderly patients. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov/ct2/home. Unique identifier: NCT0069999.

PMID- 23852611
TI  - Chewing problems are associated with depression in the elderly: results from the
      InCHIANTI study.
AB  - OBJECTIVE: Depression is increasingly recognized in older populations and
      associated with undernutrition, disability, and increased mortality. Chewing
      problems (CPs) share with depression these associations. The aim of the study was
      to evaluate the association, if any, between CPs and depression in older
      subjects. METHODS: We assessed 927 participants aged 65 years and older, derived
      from the 'InCHIANTI' study. Mood was evaluated using the CES-D scale and defined
      depressed by a CES-D score >=20. CPs were self-reported. Logistic regression was
      performed to assess the adjusted association between depression and CPs. The
      adjusted model was analyzed after stratifying for use of complete, partial
      dentures and edentulism. RESULTS: Chewing problems were reported by 293/927
      (31.6%) participants. Depression was present in 188/927(20.3%) participants. In
      multivariable logistic regression, CPs were associated with depression (OR =
      1.81, 95% CI = 1.26-2.58; p = 0.001). No significant association was found among
      subjects who used complete dentures (OR = 1.12, 95% CI = 0.80-1.58, p = 0.515).
      Up to 27.8% of prevalent depression might be attributed to CPs. CONCLUSIONS:
      Chewing problems are associated with depression in elderly population. Use of
      complete dentures hinder this association. Older depressed subjects should be
      screened for the presence of CPs; further studies are needed to evaluate the
      impact of early detection and correction of CPs on the development of depression.

PMID- 23852612
TI  - On small-sample inference in group randomized trials with binary outcomes and
      cluster-level covariates.
AB  - Group randomized trials (GRTs) randomize groups, or clusters, of people to
      intervention or control arms. To test for the effectiveness of the intervention
      when subject-level outcomes are binary, and while fitting a marginal model that
      adjusts for cluster-level covariates and utilizes a logistic link, we develop a
      pseudo-Wald statistic to improve inference. Alternative Wald statistics could
      employ bias-corrected empirical sandwich standard error estimates, which have
      received limited attention in the GRT literature despite their broad utility and
      applicability in our settings of interest. The test could also be carried out
      using popular approaches based upon cluster-level summary outcomes. A simulation
      study covering a variety of realistic GRT settings is used to compare the
      accuracy of these methods in terms of producing nominal test sizes. Tests based
      upon the pseudo-Wald statistic and a cluster-level summary approach utilizing the
      natural log of observed cluster-level odds worked best. Due to weighting, some
      popular cluster-level summary approaches were found to lead to invalid inference
      in many settings. Finally, although use of bias-corrected empirical sandwich
      standard error estimates did not consistently result in nominal sizes, they did
      work well, thus supporting the applicability of marginal models in GRT settings. 

PMID- 23852613
TI  - Super-hydrated zeolites: pressure-induced hydration in natrolites.
AB  - High-pressure synchrotron X-ray powder diffraction studies of a series of alkali
      metal-exchanged natrolites, A16Al16Si24O80.nH2O (A=Li, K, Na, Rb, and Cs and
      n=14, 16, 22, 24, 32), in the presence of water, reveal structural changes that
      far exceed what can be achieved by varying temperature and chemical composition.
      The degree of volume expansion caused by pressure-induced hydration (PIH) is
      inversely proportional to the non-framework cation radius. The expansion of the
      unit-cell volume through PIH is as large as 20.6% in Li-natrolite at 1.0 GPa and
      decreases to 6.7, 3.8, and 0.3% in Na-, K-, and Rb-natrolites, respectively. On
      the other hand, the onset pressure of PIH appears to increase with non-framework
      cation radius up to 2.0 GPa in Rb-natrolite. In Cs-natrolite, no PIH is observed
      but a new phase forms at 0.3 GPa with a 4.8% contracted unit cell and different
      cation-water configuration in the pores. In K-natrolite, the elliptical channel
      undergoes a unique overturn upon the formation of super-hydrated natrolite
      K16Al16Si24O80.32H2O at 1.0 GPa, a species that reverts back above 2.5 GPa as the
      potassium ions interchange their locations with those of water and migrate from
      the hinge to the center of the pores. Super-hydrated zeolites are new materials
      that offer numerous opportunities to expand and modify known chemical and
      physical properties by reversibly changing the composition and structure using
      pressure in the presence of water.

PMID- 23852614
TI  - Investigation of an alternative generic model for predicting pharmacokinetic
      changes during physiological stress.
AB  - Physiologically based pharmacokinetic models were developed using MATLAB
      Simulink(r) and PK-Sim(r). We compared the capability and usefulness of these two
      models by simulating pharmacokinetic changes of midazolam under exercise and heat
      stress to verify the usefulness of MATLAB Simulink(r) as a generic PBPK modeling
      software. Although both models show good agreement with experimental data
      obtained under resting condition, their predictions of pharmacokinetics changes
      are less accurate in the stressful conditions. However, MATLAB Simulink(r) may be
      more flexible to include physiologically based processes such as oral absorption
      and simulate various stress parameters such as stress intensity, duration and
      timing of drug administration to improve model performance. Further work will be
      conducted to modify algorithms in our generic model developed using MATLAB
      Simulink(r) and to investigate pharmacokinetics under other physiological stress
      such as trauma. 

PMID- 23852616
TI  - The mode of delivery in patients with preeclampsia at term subject to elective or
      emergency Cesarean section.
AB  - PURPOSE: Preeclampsia is accompanied by high maternal and fetal morbidity and
      mortality. Thus, delivery needs to be planned carefully. The aim of this study
      was to determine the most favorable delivery for patients with preeclampsia
      between the week 37 and 41 of gestation. METHODS: For this retrospective study,
      patient data from 2003 to 2011 was collected. Study participants were women
      having a Cesarean section during week 37 and 41 of gestation. The population was
      classified into four groups: patients without hypertensive disorders having an
      elective or emergency Cesarean section and patients suffering from preeclampsia
      with elective or emergency Cesarean section. Analysis included mode of delivery
      and neonatal outcome, defined by Apgar score, rate of NICU admission and pH value
      of the umbilical cord. RESULTS: A total of 130 cases of preeclampsia were
      recorded. Compared to the control group, we observed a significantly higher Apgar
      score in the study group with emergency Cesarean section. Furthermore, within the
      study group the Apgar score at 5 and 10 min was also significantly increased in
      cases delivered by emergency Cesarean section. Moreover, the pH value of the
      umbilical cord was significantly higher in the study group. Considering the
      delivery mode, significant differences were found in favor of the elective
      Cesarean section. There were no differences in the rate of NICU admission between
      the groups. CONCLUSION: The most frequent mode of delivery for women suffering
      from preeclampsia is elective Cesarean section; however, neonates delivered by
      emergency Cesarean section did not show an adverse neonatal outcome.

PMID- 23852615
TI  - Potential benefits of rho-kinase inhibition in arterial hypertension.
AB  - Arterial hypertension is a major health problem, accounting for 12 % of the
      global death rate. A large proportion of patients treated for high blood pressure
      do not reach target blood pressure values. The question arises if new
      antihypertensive drugs could improve present hypertension treatment. Rho-kinases
      (ROCKs) are ubiquitously expressed serine/threonine kinases and involved in a
      variety of cell functions. They contribute to the pathogenesis of human and
      experimental hypertension. Pharmacological ROCK inhibition has been shown to
      effectively lower blood pressure in patients and experimental animals. Progress
      has been made towards the understanding on how non-selective ROCK inhibitors
      lower arterial pressure and efforts are currently undertaken to develop ROCK
      inhibitors to improve their specificity and isoenzyme selectivity. If
      introduction of ROCK inhibitors for the treatment of high blood pressure can
      significantly advance currently available options of antihypertensive
      pharmacotherapy awaits further experimental and clinical research.

PMID- 23852617
TI  - Common polymorphisms in the CYP1A1 and CYP11A1 genes and polycystic ovary
      syndrome risk: a meta-analysis and meta-regression.
AB  - AIM: Increasing scientific evidences suggest that common polymorphisms in the
      CYP1A1 and CYP11A1 genes may contribute to the development and progression of
      polycystic ovary syndrome (PCOS), but many existing studies have yielded
      inconclusive results. The aim of this study was to perform a meta-analysis of
      published studies on the associations between common polymorphisms in the CYP1A1
      and CYP11A1 genes and susceptibility to PCOS. METHODS: An extensive literature
      search for relevant studies was conducted on PubMed, Embase, Web of Science,
      Cochrane Library, and CBM databases from their inception through 1 June, 2013.
      This meta-analysis was performed using the STATA 12.0 software. The crude risk
      ratio (RR) with 95% confidence interval was calculated. RESULTS: Thirteen case
      control studies were included in this meta-analysis with a total of 1,571 PCOS
      cases and 1,918 healthy controls. Our meta-analysis revealed that CYP1A1 MspI
      (rs4646903 T > C) polymorphism may increase the risk of PCOS, especially among
      Caucasian populations. Furthermore, CYP11A1 microsatellite [TTTA]n repeat
      polymorphism also showed significant associations with increased risk of PCOS
      among Caucasian populations. However, there was no statistically significant
      association between CYP1A1 Ile462Val (rs1048943 A > G) polymorphism and PCOS
      risk. CONCLUSION: Our meta-analysis suggests that CYP1A1 MspI and CYP11A1
      microsatellite [TTTA]n repeat polymorphisms may contribute to increasing
      susceptibility to PCOS among Caucasian populations. Detection of common
      polymorphisms in the CYP1A1 and CYP11A1 genes might be promising biomarkers for
      the diagnosis and prognosis of PCOS.

PMID- 23852619
TI  - Enhanced transgene expression in mammalian cells by recombinant baculovirus
      vector containing bovine papillomavirus type 1 replication elements.
AB  - BACKGROUND: The baculovirus Autographa californica multiple nucleopolyhedrovirus
      has been widely explored as a transgene expression vector. Further improvement of
      the expression of the transgene is important for its application. METHODS: Bovine
      papillomavirus type 1 (BPV-1) cis-element upstream regulatory region (URR) and
      trans-elements E1, E2, were inserted into the baculovirus genome. The expression
      of reporter gene, enhanced green fluorescent protein gene (EGFP), and the
      persistence of viral genome was compared in several mammalian cell lines after
      virus transduction. The cytotoxicity of the recombinant viruses was also
      evaluated. RESULTS: The recombinant baculovirus containing URR and E1, E2 genes
      showed significantly increased expression of EGFP in all cell lines tested,
      including HEK293, HeLa, BHK-21, CNE, CHO and MDCK cells. In HEK293 cells, the
      total production of EGFP was approximately five-fold higher than the control. The
      genome of virus with BPV-1 elements also persisted better than the control virus
      during the first few days post transduction. No obvious cytotoxicity was
      observed. CONCLUSIONS: The coexistence of BPV-1 URR and E1, E2 was essential and
      sufficient to improve the performance of baculovirus with respect to mediating
      gene expression in various mammalian cells without major cytotoxicity. The
      results obtained in the present study facilitate the application of baculovirus
      as an efficient transgene vehicle for protein production and gene delivery.

PMID- 23852620
TI  - Writing about stress: the impact of a stress-management programme on staff
      accounts of dealing with stress.
AB  - BACKGROUND: Helping staff serving clients with intellectual disability and
      challenging behaviour to cope with stress has implications for their own well
      being and for the lives of those they support. METHOD: This study examined staff
      members' views of stress and the effectiveness of a stress-management
      intervention. Effectiveness was assessed using written assignments regarding
      stress management, and changes in views presented were tested in a pre- and post
      test control group design. RESULTS: In the first phase, a content analysis was
      conducted across groups, which revealed that participants expressed a broad
      variety of views about stress and coping mechanisms, with considerable individual
      differences. In the second phase, a more fine-grained quantitative analysis was
      conducted to assess training effectiveness. Results showed an increase in the
      proportion of coping strategies referred to by the experimental group post
      training. This positive change remained at follow-up. CONCLUSIONS: The results of
      the content analysis and the outcome data have implications for staff training.

PMID- 23852618
TI  - Age-related histological and zinc content changes in adult nonhyperplastic
      prostate glands.
AB  - To clarify age-related histological and Zn content changes in nonhyperplastic
      adult prostate glands, a quantitative morphometric and energy-dispersive X-ray
      fluorescence analyses were performed. The prostates were obtained from autopsies
      of 63 subjects aged 21-70 years who died mainly from trauma. It was found that
      histologically normal prostate tissue undergoes substantial changes throughout
      aging. These changes are reflected in an increase of the percent volume of the
      glandular lumen for the third to fifth decades, reaching a maximum for the decade
      41-50 years. Over the same period, the percent volume of the stroma remains
      steady, but the percent volume of epithelium decreases, approximately, linearly
      with age. The percent volume of glandular lumen (reflects the volume of prostatic
      fluid) in the prostate gland of men aged 41 to 50 years is 1.5-fold higher than
      that in men aged 21 to 30 years, but the epithelium/lumen (prostatic fluid) ratio
      is approximately twofold lower. This suggests that accumulation of the prostatic
      fluid develops from 30 to 50 years of age. This accumulation of the prostatic
      fluid results in an increase of the Zn mass fraction in the prostate. In turn,
      when the intraprostatic Zn level exceeds a certain level by the end of the fifth
      decade, it begins to work as a trigger for different factors, all of which
      increase the proliferation of stromal cells. Deductions from these results allow
      possible partial explanations of both relevant prostatic aging mechanisms and the
      effects of dietary interventions using supplementary Zn.

PMID- 23852621
TI  - Trends in intracranial meningioma surgery and outcome: a Nationwide Inpatient
      Sample database analysis from 2001 to 2010.
AB  - The objective of the present study was to analyze the risk of in-patient
      mortality, adverse outcome, practice patterns and regional variations in patients
      who underwent intracranial meningioma surgery in the United States between 2001
      and 2010. We performed a retrospective cohort study using the Nationwide
      Inpatient Sample database. In-patient mortality and adverse outcome at discharge
      were the outcome predictors. Multivariate analyses were done to analyze the
      patient, hospital and physician characteristics. The annual case-volume of
      patients with meningioma increased from 2001 to 2010 by 40 %. The in-patient
      mortality rate remained the same at 1.3 % and the rate of adverse discharge
      disposition remained at 35 % between 2001 and 2010. Caucasian female patients in
      younger age group with private insurance who underwent treatment at a high case
      volume center had the best outcomes. In older patients (>=70 years), the in
      patient mortality rate decreased by 25 % whereas the adverse discharge
      disposition rate increased by 19 %. Patients treated at high case-volume centers
      and by high case-volume physicians had lower rates of in-patient mortality (P <
      0.05) and adverse outcome at discharge (P = 0 < 0.05). There was a 54 % decrease
      in the number of hospitals performing one surgery/year through the decade. A 2 %
      relative decrease in mortality was observed in lowest volume hospitals. Though
      the highest increase in admission charges through the decade was seen in
      hospitals located in the north-east (165 % relative increase), the highest
      relative decrease in mortality and morbidity was observed in hospitals located in
      the mid-west and the south (67.6 and 22 % respectively).

PMID- 23852622
TI  - Noncovalent chiral functionalization of graphene with optically active helical
      polymers.
AB  - Optically active helical substituted (co)polyacetylenes containing pendent pyrene
      groups are prepared and then noncovalently immobilized on graphene via pi-pi
      interactions. The resulting graphene composite is characterized by XRD, FTIR,
      Raman, circular dichroism, UV-vis absorption, TEM, TGA, and fluorescent
      spectroscopy techniques. The helical polyacetylene endows graphene with the
      desired optical activity. Also interestingly, the dispersibility of the
      functionalized graphene in tetrahydrofuran is remarkably improved due to the
      presence of the helical polymer chains. The present methodology opens new
      opportunities and serves as a versatile platform toward preparing novel graphene
      based materials. 

PMID- 23852624
TI  - Burden of lysosomal storage disorders in India: experience of 387 affected
      children from a single diagnostic facility.
AB  - Lysosomal storage disorders (LSDs) are considered to be a rare metabolic disease
      for the national health forum, clinicians, and scientists. This study aimed to
      know the prevalence of different LSDs, their geographical variation, and burden
      on the society. It included 1,110 children from January 2002 to December 2012,
      having coarse facial features, hepatomegaly or hepatosplenomegaly, skeletal
      dysplasia, neuroregression, leukodystrophy, developmental delay, cerebral
      cerebellar atrophy, and abnormal ophthalmic findings. All subjects were screened
      for I-cell disease, glycolipid storage disorders (Niemann-Pick disease A/B,
      Gaucher), and mucopolysaccharide disorders followed by confirmatory lysosomal
      enzymes study from leucocytes and/or fibroblasts. Niemann-Pick disease-C (NPC)
      was confirmed by fibroblasts study using filipin stain. Various storage disorders
      were detected in 387 children (34.8 %) with highest prevalence of glycolipid
      storage disorders in 48 %, followed by mucopolysaccharide disorders in 22 % and
      defective sulfatide degradation in 14 % of the children. Less common defects were
      glycogen degradation defect and protein degradation defect in 5 % each, lysosomal
      trafficking protein defect in 4 %, and transport defect in 3 % of the patients.
      This study demonstrates higher incidence of Gaucher disease (16 %) followed by
      GM2 gangliosidosis that includes Tay-Sachs disease (10 %) and Sandhoff disease
      (7.8 %) and mucopolysaccharide disorders among all LSDs. Nearly 30 % of the
      affected children were born to consanguineous parents and this was higher (72 %)
      in children with Batten disease. Our study also demonstrates two common mutations
      c.1277_1278insTATC in 14.28 % (4/28) and c.964G>T (p.D322Y) in 10.7 % (3/28) for
      Tay-Sachs disease in addition to the earlier reported c.1385A>T (p.E462V)
      mutation in 21.42 % (6/28). 

PMID- 23852625
TI  - A novel coculture model of HUVECs and HUASMCs by hyaluronic acid micropattern on
      titanium surface.
AB  - Orientation smooth muscle cell environment plays a positive role in the
      development of a functional, adherent endothelium. Therefore, building an
      orientation coculture model of endothelial cells (ECs) and smooth muscle cells
      (SMCs) on biomaterials surface may provide more help for understanding the
      interaction between the two cells in vitro. In the present study, a "SMCs-ColIV
      ECs" coculture model was built on the hyaluronic acid (HA) patterned titanium
      (Ti) surface, and compared with the previous "SMCs-HAa-ECs" model on endothelial
      cell number, morphology index, nitric oxide (NO), and prostacyclin2 (PGI2)
      release, anticoagulation property, human umbilical artery smooth muscle cells
      (HUASMCs) inhibition property and retention under fluid flow shear stress. The
      result indicated that "SMCs-ColIV-ECs" model could enhance the number, spreading
      area, and major/minor index of human umbilical vein endothelial cells (HUVECs),
      which contributed to the retention of HUVECs on the surface. Greater major/minor
      index may produce more NO and PGI2 release, contributing to the anticoagulation
      property and HUASMCs inhibition property. In summary, this novel "SMCs-ColIV-ECs"
      coculture model improved the previous "SMCs-HAa-ECs" model, and may provide more
      inspiration for the human vascular intima building on the biomaterials in vitro.

PMID- 23852626
TI  - Anticancer potency and multidrug-resistant studies of self-assembled arene
      ruthenium metallarectangles.
AB  - A suite of three tetraruthenium metallacycles have been obtained from [2+2] self
      assemblies between N,N'-Di-(4-pyridyl)-1,4,5,8-naphthalenetetracarbo-xydiimide
      (4) and one of the three dinuclear arene ruthenium clips, (eta(6)-p
      iPrC6H4Me)2Ru2(OO?OO)][OTf]2 (OO?OO = oxalate 1, 2,5-dioxydo-1,4-benzoquinonato
      (dobq) 2, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 3; OTf = triflate). All
      complexes were isolated in good yield (>85 %) as triflate salts and were fully
      characterized by using (1)H NMR and UV/Vis spectroscopies, and high-resolution
      electrospray mass spectrometry. A single crystal of the metallarectangle 5 was
      suitable for X-ray diffraction structural characterization. The biological
      activities of the metallacycles were determined by using 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, establishing their in vitro
      anticancer properties. Our results show that for the AGC (gastric cancer) cell
      lines, the cytotoxicity of (donq)-containing SCC 7 exceeds that of cisplatin,
      which was used as a control. For HCT15 (colon cancer) cell lines, the
      cytotoxicity is comparable to both cisplatin and doxorubicin. An in vivo hollow
      fiber model was used to show growth-inhibitory activity against HCT15 and image
      based cytometry experiments indicated that 7 induced apoptosis as the mode of
      cell death. Complex 7 also showed significant antitumor activity for multidrug
      resistant HCT15/CLO2 cell lines, for which doxorubicin was ineffective.

PMID- 23852627
TI  - Founding an adverse drug reaction (ADR) network: a method for improving doctors
      spontaneous ADR reporting in a general hospital.
AB  - Adverse drug reactions (ADR) are underreported by doctors despite numerous
      efforts. We aimed to determine if establishing an "ADR reporting doctor's
      network" within a hospital would increase the quantity of ADRs reported by
      hospital doctors. One hundred hospital doctors joined the network. Email
      reminders were sent to network members during the 1 year study period, conveying
      information about ADRs reported, amusingly and pleasantly reminding them to
      report ADRs in minimal detail, by phone, email, text message or mail to the
      Clinical Pharmacology Unit, who would further complete the report. A total of 114
      ADRs were reported during the study period in comparison to 48, 26, and 17 in the
      previous 3 years (2008, 2009, 2010, respectively). In the 3 years prior, doctors
      reported 41.7% of the reported ADRs whereas in the study period, doctors reported
      74.3% of ADRs (P < .001), reflecting an 80% increase in doctors reports. Ninety
      seven percent of doctors' reports were of ADR network members. Thirty-four (34%)
      network members reported an ADR during the study period and 31 of the 34
      reporters had never reported ADRs before becoming network members. Establishing
      an ADR network of doctors substantially increases ADR reporting amongst its
      members. 

PMID- 23852628
TI  - A Wireless IC for Wide-Range Neurochemical Monitoring Using Amperometry and Fast
      Scan Cyclic Voltammetry.
AB  - An integrated circuit for real-time wireless monitoring of neurochemical activity
      in the nervous system is described. The chip is capable of conducting
      measurements in both fast-scan cyclic voltammetry (FSCV) and amperometry modes
      for a wide input current range. The chip architecture employs a second-order
      DeltaSigma modulator (DeltaSigmaM) and a frequency-shift-keyed transmitter
      operating near 433 MHz. It is fabricated using the AMI 0.5-mum double-poly triple
      metal n-well CMOS process, and requires only one off-chip component for
      operation. A measured current resolution of 12 pA at a sampling rate of 100 Hz
      and 132 pA at a sampling rate of 10 kHz is achieved in amperometry and 300-V/s
      FSCV modes, respectively, for any input current in the range of plusmn430 nA. The
      modulator core and the transmitter draw 22 and 400 muA from a 2.6-V power supply,
      respectively. The chip has been externally interfaced with a carbon-fiber
      microelectrode implanted acutely in the caudate-putamen of an anesthetized rat,
      and, for the first time, extracellular levels of dopamine elicited by electrical
      stimulation of the medial forebrain bundle have been successfully recorded
      wirelessly using 300-V/s FSCV. 

PMID- 23852629
TI  - Stimulus-artifact elimination in a multi-electrode system.
AB  - To fully exploit the recording capabilities provided by current and future
      generations of multi-electrode arrays, some means to eliminate the residual
      charge and subsequent artifacts generated by stimulation protocols is required.
      Custom electronics can be used to achieve such goals, and by making them
      scalable, a large number of electrodes can be accessed in an experiment. In this
      work, we present a system built around a custom 16-channel IC that can stimulate
      and record, within 3 ms of the stimulus, on the stimulating channel, and within
      500 mus on adjacent channels. This effectiveness is achieved by directly
      discharging the electrode through a novel feedback scheme, and by shaping such
      feedback to optimize electrode behavior. We characterize the different features
      of the system that makes such performance possible and present biological data
      that show the system in operation. To enable this characterization, we present a
      framework for measuring, classifying, and understanding the multiple sources of
      stimulus artifacts. This framework facilitates comparisons between artifact
      elimination methodologies and enables future artifact studies. 

PMID- 23852630
TI  - A frequency control method for regulating wireless power to implantable devices.
AB  - This paper presents a method to regulate the power transferred over a wireless
      link by adjusting the resonant operating frequency of the primary converter. A
      significant advantage of this method is that effective power regulation is
      maintained under variations in load, coupling and circuit parameters. This is
      particularly important when the wireless supply is used to power implanted
      medical devices where substantial coupling variations between internal and
      external systems is expected. The operating frequency is changed dynamically by
      altering the effective tuning capacitance through soft switched phase control. A
      thorough analysis of the proposed system has been undertaken, and experimental
      results verify its functionality. 

PMID- 23852631
TI  - An active 2-d silicon cochlea.
AB  - In this paper, we present an analog integrated circuit design for an active 2-D
      cochlea and measurement results from a fabricated chip. The design includes a
      quality factor control loop that incorporates some of the nonlinear behavior
      exhibited in the real cochlea. This control loop varies the gain and the
      frequency selectivity of each cochlear resonator based on the amplitude of the
      input signal. 

PMID- 23852632
TI  - A Mini-Invasive Long-Term Bladder Urine Pressure Measurement ASIC and System.
AB  - A mini-invasive system for long-term bladder urine pressure measurement system is
      presented. Not only is the design cost reduced, but also the reliability is
      enhanced by using a 1-atm canceling sensing instrumentation amplifier (IA).
      Because the urine pressure inside the bladder does not vary drastically, both the
      sleeping and working modes are required in order to save the battery power for
      long-term observation. The IA amplifies the signal sensed by the pressure sensor,
      which is then fed into the following analog-to-digital converter. Owing to the
      intrinsic 1-atm pressure existing inside the bladder, the IA must be able to
      cancel such a pressure from the signal picked up by the pressure sensor to keep
      the required linearity and the resolution for pressure measurement of the bladder
      urine. The pressure range of the proposed system is found out to be 14.7~19.7
      Psi, which covers the range of all of the known unusual bladder syndromes or
      complications. 

PMID- 23852633
TI  - Defect-aware high-level synthesis and module placement for microfluidic biochips.
AB  - Recent advances in microfluidics technology have led to the emergence of
      miniaturized biochip devices, also referred to as lab-on-a-chip, for biochemical
      analysis. A promising category of microfluidic biochips relies on the principle
      of electrowetting-on-dielectric, whereby discrete droplets of nanoliter volumes
      can be manipulated using an array of electrodes. As chemists adapt more bioassays
      for concurrent execution on such ldquodigitalrdquo droplet-based microfluidic
      platforms, system integration, design complexity, and the need for defect
      tolerance are expected to increase rapidly. Automated design tools for defect
      tolerant and multifunctional biochips are important for the emerging marketplace,
      especially for low-cost, portable, and disposable devices for clinical
      diagnostics. We present a unified synthesis method that combines defect-tolerant
      architectural synthesis with defect-aware physical design. The proposed approach
      allows architectural-level design choices and defect-tolerant physical design
      decisions to be made simultaneously. We use a large-scale protein assay and the
      polymerase chain reaction procedure as case studies to evaluate the proposed
      synthesis method. We also carry out simulations based on defect injection to
      evaluate the robustness of the synthesized biochip designs. 

PMID- 23852634
TI  - Au@poly(N-propargylamide) nanoparticles: preparation and chiral recognition.
AB  - This communication reports the first gold nanoparticles (NPs) chirally
      functionalized with optically active helical substituted polyacetylene (the
      resulting hybrid particles are defined as Au@PPA NPs). The novel nanoparticles
      consist of gold as core and optically active helical poly(N-propargylamide) as
      shell and show considerable optical activity derived from helical poly(N
      propargylamide) chains with predominantly one-handed screw sense. The Au@PPA NPs
      are prepared by a three-step approach: i) a thiol-containing N-propargylamide
      monomer [Mth , HC=CCH2 NHCO(CH2 )10 SH] is synthesized and characterized with
      FTIR and(1) HNMR spectroscopy and elemental analysis; ii) a copolymer (poly(Mth 
      co-Mch )) was prepared by starting from monomer Mth and another chiral N
      propargylamide monomer (Mch ); poly(Mth -co-Mch ) formed helical conformations
      and showed optical activities; and, iii) Au@PPA NPs are prepared from hydrogen
      tetrachloroaurate (III) and poly(Mth -co-Mch ) through a one-spot procedure by
      using LiBH4 as reducing agent. The as-obtained hybrid nanoparticles are
      characterized by FTIR spectroscopy, TEM, UV-vis absorption and circular dichroism
      (CD) techniques. UV-vis and CD measurements demonstrated the remarkable optical
      activity of the Au@PPA NPs. More interestingly, the Au@PPA NPs show much stronger
      UV-vis and CD sigals when compared to the corresponding orginal helical
      copolymer, poly(Mth -co-Mch ). The chiral hybrid nanoparticles demonstrate
      different absorption toward (R)-(+)- and (S)-(-)-1-phenylethylamines,
      preferentially adsorbing the (S)-isomer. 

PMID- 23852635
TI  - Experimental analysis of co-evolution within protein complexes: the yeast exosome
      as a model.
AB  - Extensive bioinformatics analysis suggests that the stability and function of
      protein complexes are maintained throughout evolution by coordinated changes (co
      evolution) of complex subunits. Yet, relatively little is known regarding the
      actual dynamics of such processes and the functional implications of co-evolution
      within protein complexes, since most of the bioinformatics predictions were not
      analyzed experimentally. Here, we describe a systematic experimental approach
      that allows a step-by-step observation of the co-evolution process in protein
      complexes. The exosome complex, an essential complex exhibiting a 3'->5' RNA
      degradation activity, served as a model system. In this study, we show that
      exosome subunits diverged very early during fungal evolution. Interestingly, we
      found that despite significant differences in conservation between Rrp41 and Mtr3
      both subunits exhibit similar divergence pattern and co-evolutionary behavior
      through fungi evolution. Activity analysis of mutated exosomes exposes another
      layer of co-evolution between the core subunits and RNA substrates. Overall, our
      approach allows the experimental analysis of co-evolution within protein
      complexes and together with bioinformatics analysis can significantly deepen our
      understanding of the evolution of these complexes.

PMID- 23852637
TI  - The information security needs in radiological information systems-an insight on
      state hospitals of Iran, 2012.
AB  - Picture Archiving and Communications System (PACS) was originally developed for
      radiology services over 20 years ago to capture medical images electronically.
      Medical diagnosis methods are based on images such as clinical radiographs,
      ultrasounds, CT scans, MRIs, or other imaging modalities. Information obtained
      from these images is correlated with patient information. So with regards to the
      important role of PACS in hospitals, we aimed to evaluate the PACS and survey the
      information security needed in the Radiological Information system. First, we
      surveyed the different aspects of PACS that should be in any health organizations
      based on Department of Health standards and prepared checklists for assessing the
      PACS in different hospitals. Second, we surveyed the security controls that
      should be implemented in PACS. Checklists reliability is affirmed by professors
      of Tehran Science University. Then, the final data are inputted in SPSS software
      and analyzed. The results indicate that PACS in hospitals can transfer patient
      demographic information but they do not show route of information. These systems
      are not open source. They don't use XML-based standard and HL7 standard for
      exchanging the data. They do not use DS digital signature. They use passwords and
      the user can correct or change the medical information. PACS can detect
      alternation rendered. The survey of results demonstrates that PACS in all
      hospitals has the same features. These systems have the patient demographic data
      but they do not have suitable flexibility to interface network or taking reports.
      For the privacy of PACS in all hospitals, there were passwords for users and the
      system could show the changes that have been made; but there was no water making
      or digital signature for the users. 

PMID- 23852636
TI  - Vascular sarcomas.
AB  - Vascular sarcomas are soft-tissue tumors that arise from the endothelium with a
      malignant potential. This review discusses the management of epithelioid
      hemangioendothelioma (EHE) and angiosarcoma. EHE is a vascular tumor of
      intermediate malignant potential with an indolent course. EHE arising from the
      liver, lung, or bone tends to be multifocal and the rate of progression is slow
      and often unpredictable. Treatment should be considered in patients with
      significant symptomatic deterioration and/or progressive disease on imaging
      studies. Various cytotoxic and targeted therapies are available for management,
      with disease stabilization as the most common outcome. Angiosarcoma is an
      aggressive vascular tumor with a high malignant potential. Multidisciplinary care
      is critical for the management of localized disease, and the best outcomes are
      often observed in patients when a combination of systemic and local therapy
      options is used. Metastatic angiosarcoma is treated primarily with systemic
      therapy, and several cytotoxic and targeted therapies are available, alone or in
      combination. The choice of therapy depends on several factors, such as cutaneous
      location of the tumor, performance status of the patient, toxicity of the
      treatment, and patient goals. 

PMID- 23852638
TI  - Rapid and sensitive analysis of euonine and wilforidine in human plasma by high
      performance liquid chromatography-atmospheric-pressure chemical ionization-mass
      spectrometry.
AB  - Euonine and wilforidine are biologically active Tripterygium wilfordii Hook. f.
      alkaloids. In this paper, a rapid and sensitive high-performance liquid
      chromatography-mass spectrometry (MS) method was developed and validated for the
      simultaneous determination of trace euonine and wilforidine in human plasma. An
      Oasis(r) mixed-mode cation-exchange polymeric sorbent was used for solid-phase
      extraction. The separation was carried out on a reversed-phase Zorbax Plus C18
      column (50 mm * 2.1 mm, 1.8 MUm) by using ammonium acetate (5
      mmol/L)/acetonitrile (30/70, v/v) as the mobile phase at a flow rate of 0.7
      mL/min. The quantification was carried out via ion trap MS in the positive
      selected ion monitoring mode using aconitine as an internal standard. Calibration
      curves showed good linearity ranging from 0.5 to 100.0 MUg/L with correlation
      coefficient values >0.9990. The average recoveries of euonine and wilforidine
      ranged from 85.4 to 101.0% and 92.0 to 97.5%, respectively. The intra- and
      interday relative standard deviations were <8.7 and 12.9%, respectively. The
      limits of quantification for both euonine and wilforidine were 0.5 MUg/L, which
      is suitable in the clinical pharmaceutical research of volunteer patients with
      rheumatoid arthritis.

PMID- 23852639
TI  - The effect of ovarian stimulation on the outcome of intrauterine insemination.
AB  - PURPOSE: Although intrauterine insemination is one of the oldest techniques in
      reproductive medicine, its significance is still controversially discussed. Many
      factors have been reported as influencing pregnancy rates after IUI. The aim of
      this retrospective analysis is to evaluate the success rate of repeated
      inseminations depending on the type of ovarian stimulation. METHODS: Patients who
      underwent intrauterine insemination in Wiesbaden Kinderwunschzentrum between 1998
      and 2010, not older than 45 years of age, with male subfertility were included in
      this study. On the whole, 5,346 inseminations on 2,180 patients were analyzed
      retrospectively. RESULTS: Females' mean age was 34.1, ranging from 19-45 years.
      In 433 cycles an insemination was performed during a natural cycle. 4,020 cycles
      were stimulated with recombinant FSH, 596 cycles with clomiphene, 194 with
      urinary FSH, 103 with HMG. The pregnancy rates range from 7.4% in the clomiphene
      group to 14.4% in the urinary FSH group. Clomiphene stimulation seems to offer
      the significantly lowest pregnancy rate (p = 0.03). The other types of
      stimulation do not differ significantly from each other concerning the pregnancy
      rate. Patients under 39 years of age do not profit from any ovarian stimulation.
      In 40 and more years of old patients, pregnancy rates are higher, if any
      stimulation was performed. CONCLUSION: To sum up, clomiphene stimulation showed
      to offer significantly lower pregnancy rates in comparison to the natural cycle,
      FSH stimulation and HMG stimulation in IUI treatment. While women younger than 40
      seem not to profit from any ovarian stimulation, women over 40 do profit.

PMID- 23852640
TI  - Pregnancy outcome in patients with idiopathic thrombocytopenic purpura.
AB  - OBJECTIVE: To study the outcome of pregnancy in women with idiopathic
      thrombocytopenic purpura. MATERIALS AND METHODS: A retrospective analysis of 30
      pregnancies in 26 women with idiopathic thrombocytopenic purpura was carried out
      at a tertiary hospital in India. The courses of the disease, maternal and
      perinatal outcome in these pregnancies were studied. RESULTS: Mean age of
      pregnant women with idiopathic thrombocytopenic purpura was 27.3 years and 61.5 %
      was primigravidae. Out of 26 patients with idiopathic thrombocytopenic purpura,
      16 were already diagnosed while the other 10 were diagnosed during pregnancy. The
      incidence of bleeding episodes in antenatal period, severe thrombocytopenia and
      hemorrhagic complications at the time of delivery was 30, 37 and 11.1 %,
      respectively. Oral steroids were required in 40 % of pregnancies. Two patients
      received intravenous immunoglobulin therapy. Severe thrombocytopenia at the time
      of delivery was more commonly seen in women in whom ITP was diagnosed during
      pregnancy as compared to those in whom ITP was diagnosed prior to pregnancy (P =
      0.04). Severe thrombocytopenia was seen in 18.5 % of neonates and intracranial
      hemorrhage was detected in 1 neonate. There were no still births or maternal
      mortality. CONCLUSION: Pregnancy outcome in patients with idiopathic
      thrombocytopenic purpura is generally good.

PMID- 23852641
TI  - Functional role of beta domain in the Thermoanaerobacter tengcongensis
      glucoamylase.
AB  - Thermoanaerobacter tengcongensis MB4 glucoamylase (TteGA) contains a catalytic
      domain (CD), which is structurally similar to eukaryotic GA, and a beta domain
      (BD) with ambiguous function. Firstly, BD is found to be essential to TteGA
      activity because CD alone could not hydrolyze soluble starch. However, starch
      hydrolysis activity, similar to that of intact TteGA, was restored to CD in the
      presence of BD. Secondly, BD is found to be an important helper in the correct
      folding of CD because CD was mainly expressed in the inclusion bodies on its own
      in Escherichia coli. By contrast, intact TteGA, BD, and CD combined with BD could
      be expressed as soluble proteins. Additionally, BD is essential to the
      thermostability of TteGA because CD displayed lower thermostability compared with
      the intact TteGA and exhibited enhanced thermostability in the presence of BD in
      vitro. Truncation of TteGA or mutagenesis of the residues that participate in the
      interdomain interaction at its BD also led to the reduced thermostability of
      TteGA. 

PMID- 23852642
TI  - Characterization of stable, constitutively expressed, chromosomal green and red
      fluorescent transcriptional fusions in the select agent bacterium, Francisella
      tularensis Schu S4 and the surrogate type B live vaccine strain (LVS).
AB  - Here, we constructed stable, constitutively expressed, chromosomal green (GFP)
      and red fluorescent (RFP) reporters in the genome of the surrogate strain,
      Francisella tularensis spp. holarctica LVS (herein LVS), and the select agent, F.
      tularensis Schu S4. A bioinformatic approach was used to identify constitutively
      expressed genes. Two promoter regions upstream of the FTT1794 and rpsF(FTT1062)
      genes were selected and fused with GFP and RFP reporter genes in pMP815,
      respectively. While the LVS strains with chromosomally integrated reporter
      fusions exhibited fluorescence, we were unable to deliver the same fusions into
      Schu S4. Neither a temperature-sensitive Francisella replicon nor a pBBR replicon
      in the modified pMP815 derivatives facilitated integration. However, a mini-Tn7
      integration system was successful at integrating the reporter fusions into the
      Schu S4 genome. Finally, fluorescent F. tularensis LVS and a mutant lacking MglA
      were assessed for growth in monocyte-derived macrophages (MDMs). As expected,
      when compared to wild-type bacteria, replication of an mglA mutant was
      significantly diminished, and the overall level of fluorescence dramatically
      decreased with infection time. The utility of the fluorescent Schu S4 strain was
      also examined within infected MDMs treated with clarithromycin and enrofloxacin.
      Taken together, this study describes the development of an important reagent for
      F. tularensis research, especially since the likelihood of engineered antibiotic
      resistant strains will emerge with time. Such strains will be extremely useful in
      high-throughput screens for novel compounds that could interfere with critical
      virulence processes in this important bioweapons agent and during infection of
      alveolar macrophages.

PMID- 23852644
TI  - 3,4,5-Trimethoxycinnamic acid (TMCA), one of the constituents of Polygalae Radix
      enhances pentobarbital-induced sleeping behaviors via GABAAergic systems in mice.
AB  - These experiments were performed to investigate whether 3,4,5-trimethoxycinnamic
      acid (TMCA), one of the constituents derived from Polygalae Radix, enhances
      pentobarbital-induced sleeping behaviors, and to alter sleep architecture through
      the gamma-aminobutyric acid (GABA)ergic systems in mice. TMCA decreased the
      locomotor activity. TMCA prolonged total sleep time, and reduced sleep latency
      induced by pentobarbital, similar to muscimol, a GABAA agonist. From the
      electrocencephalogram recording for 6 h after TMCA administration, the number of
      sleep/wake cycles were reduced by TMCA. TMCA also increased the total sleep time
      and non-rapid eye movement (NREM) sleep. In addition, TMCA increased Cl(-) influx
      in primary cultured cerebellar granule cells of mice. TMCA increased the
      activation of glutamic acid decarboxylase (GAD) and the expressions of gamma
      subunit of GABAA receptors in the cerebellar granule cells. However, alpha- and
      beta-subunits proteins of GABAA receptors were not increased. Therefore, TMCA
      would increase pentobarbital induced-sleep and NREM sleep in mice. These results
      indicate that TMCA may enhance sleep and alter sleep architecture through
      GABAAergic systyems.

PMID- 23852643
TI  - The molecular basis for ethnic variation and histological subtype differences in
      prostate cancer.
AB  - Prostate cancer is a common malignancy among men in Western countries. Recently
      the morbidity and mortality of prostate cancer increase dramatically in several
      oriental countries including China. Rapidly evolving technology in molecular
      biology such as high-throughput sequencing and integrative analysis of genomic
      and transcriptomic landscapes have enabled the identification of key oncogenic
      events for prostate cancer initiation, progression and resistance to hormonal
      therapy. These surging data of prostate cancer genome also provide insights on
      ethnic variation and the differences in histological subtype of this disease. In
      this review, differences in the incidence of prostate cancer and the prevalence
      of main genetic alterations between Asian and Western populations are discussed.
      We also review the recent findings on the mechanisms underlying neuroendocrine
      differentiation of prostate cancer and the development of small cell
      neuroendocrine carcinoma after androgen deprivation therapy. 

PMID- 23852645
TI  - In situ intestinal permeability and in vivo oral bioavailability of celecoxib in
      supersaturating self-emulsifying drug delivery system.
AB  - In order to characterize the in situ intestinal permeability and in vivo oral
      bioavailability of celecoxib (CXB), a poorly water-soluble cyclooxygenase (COX)-2
      inhibitor, various formulations including the self-emulsifying drug delivery
      system (SEDDS) and supersaturating SEDDS (S-SEDDS) were compared. The S-SEDDS
      formulation was obtained by adding Soluplus as a precipitation inhibitor to
      SEDDS, composed of Capryol 90 as oil, Tween 20 as surfactant, and Tetraglycol as
      cosurfactant (1:4.5:4.5 in volume ratio). An in situ single pass intestinal
      perfusion study in rats was performed with CXB-dissolved solutions at a
      concentration of 40 MUg/mL. The effective permeability (Peff) of CXB in the
      control solution (2.5 v/v% Tween 20-containing PBS) was 6.39 * 10(-5) cm/s. The
      Peff value was significantly increased (P < 0.05) by the lipid-based formulation,
      yielding 1.5- and 2.9-fold increases for the SEDDS and S-SEDDS solutions,
      respectively, compared to the control solution. After oral administration of
      various formulations to rats at the equivalent dose of 100 mg/kg of CXB, the
      plasma drug level was measured by LC-MS/MS. The relative bioavailabilities of
      SEDDS and S-SEDDS were 263 and 355 %, respectively, compared to the CXB
      suspension as a reference. In particular, S-SEDDS revealed the highest Cmax and
      the smallest Tmax, indicating rapid and enhanced absorption with this
      formulation. This study illustrates the potential use of the S-SEDDS formulation
      in the oral delivery of poorly water-soluble compounds.

PMID- 23852646
TI  - Delivery.
AB  - Enthusiasm greeted the development of synthetic organic insecticides in the mid
      twentieth century, only to see this give way to dismay and eventually scepticism
      and outright opposition by some. Regardless of how anyone feels about this issue,
      insecticides and other pesticides have become indispensable, which creates
      something of a dilemma. Possibly as a result of the shift in public attitude
      towards insecticides, genetic engineering of microbes was first met with
      scepticism and caution among scientists. Later, the development of genetically
      modified crop plants was met with an attitude that hardened into both acceptance
      and hard-core resistance. Transgenic insects, which came along at the dawn of the
      twenty-first century, encountered an entrenched opposition. Those of us
      responsible for studying the protection of crops have been affected more or less
      by these protagonist and antagonistic positions, and the experiences have often
      left one thoughtfully mystified as decisions are made by non-participants. Most
      of the issues boil down to concerns over delivery mechanisms.

PMID- 23852647
TI  - The structurally effect of surface coated rhamnogalacturonan I on response of the
      osteoblast-like cell line SaOS-2.
AB  - Osseointegration is important when implants are inserted into the bone and can be
      improved by biochemical surface coating of the implant. In this paper
      enzymatically modified rhamnogalacturonan I (RG-I) from apple and lupin was used
      for biochemical coating of aminated surfaces and the importance of the quality of
      RG-I, the nature of the binding, the fine structure of RG-I, and its effect on
      SaOS-2 cell line cultured on coated surfaces was investigated. SaOS-2 cells are
      osteoblast-like cells and a well-established in vitro model of bone-matrix
      forming osteoblasts. Purification by gel filtration could remove small fragments
      of galacturonic acid (GalA) and binding studies showed that the purity of the RG
      I molecules was important for the quality of the coating. The structure of RG-I
      and osteoblast-like cells' viability were positively correlated so that high
      content of 1,4-linked galactose (Gal) and a low content of arabinose in the RG-I
      molecules favored cell viability. These results indicate that coating of implants
      with RG-I affect osseointegration positively.

PMID- 23852648
TI  - A phase II trial of trastuzumab combined with irinotecan in patients with
      advanced HER2-positive chemo-refractory gastric cancer: Osaka Gastrointestinal
      Cancer Chemotherapy Study Group OGSG1203 (HERBIS-5).
AB  - Irinotecan is a key drug in second- or further-line chemotherapy for patients
      with advanced gastric cancer. Continuous administration of trastuzumab beyond
      first progression is expected to contribute to the benefit of chemotherapy for
      human epidermal growth factor receptor 2-positive gastric cancer. The aim of this
      trial is to evaluate the efficacy and safety of combination chemotherapy with
      trastuzumab and irinotecan in Japanese patients with advanced human epidermal
      growth factor receptor 2-positive chemo-refractory gastric cancer. The primary
      endpoint is the disease control rate. The secondary endpoints are adverse events,
      overall response rate, time to treatment failure, progression-free survival,
      overall survival and response rate stratified by prior trastuzumab use. A total
      of 30 patients will be enrolled in this Osaka Gastrointestinal Cancer
      Chemotherapy Study Group trial. 

PMID- 23852649
TI  - Comparison of oxidative aromatic coupling and the Scholl reaction.
AB  - Does the dehydrogenative coupling of aromatic compounds mediated by AlCl3 at high
      temperatures and also by FeCl3, MoCl5, PIFA, or K3[Fe(CN)6] at room temperature
      proceed by the same mechanism in all cases? With the growing importance of the
      synthesis of aromatic compounds by double C-H activation to give various biaryl
      structures, this question becomes pressing. Since some of these reactions proceed
      only in the presence of non-oxidizing Lewis acids and some only in the presence
      of certain oxidants, the authors venture the hypothesis that, depending on the
      electronic structure of the substrates and the nature of the "catalyst", two
      different mechanisms can operate. One involves the intermediacy of a radical
      cation and the other the formation of a sigma complex between the acid and the
      substrate. The goal of this Review is to encourage further mechanistic studies
      hopefully leading to an in-depth understanding of this phenomenon.

PMID- 23852650
TI  - Adaptive deep brain stimulation in advanced Parkinson disease.
AB  - OBJECTIVE: Brain-computer interfaces (BCIs) could potentially be used to interact
      with pathological brain signals to intervene and ameliorate their effects in
      disease states. Here, we provide proof-of-principle of this approach by using a
      BCI to interpret pathological brain activity in patients with advanced Parkinson
      disease (PD) and to use this feedback to control when therapeutic deep brain
      stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing
      and optimizing stimulation in real time, we could improve on both the efficacy
      and efficiency of conventional continuous DBS. METHODS: We tested BCI-controlled
      adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was
      provided by processing of the local field potentials recorded directly from the
      stimulation electrodes. The results were compared to no stimulation, conventional
      continuous stimulation (cDBS), and random intermittent stimulation. Both
      unblinded and blinded clinical assessments of motor effect were performed using
      the Unified Parkinson's Disease Rating Scale. RESULTS: Motor scores improved by
      66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27%
      (p = 0.005) better than cDBS, respectively. These improvements were achieved with
      a 56% reduction in stimulation time compared to cDBS, and a corresponding
      reduction in energy requirements (p < 0.001). aDBS was also more effective than
      no stimulation and random intermittent stimulation. INTERPRETATION: BCI
      controlled DBS is tractable and can be more efficient and efficacious than
      conventional continuous neuromodulation for PD.

PMID- 23852651
TI  - Fatal central nervous system air embolism during elective
      esophagogastroduodenoscopy.

PMID- 23852653
TI  - Polymer-based stimuli-responsive recyclable catalytic systems for organic
      synthesis.
AB  - The introduction of stimuli-responsive polymers into the study of organic
      catalysis leads to the generation of a new kind of polymer-based stimuli
      responsive recyclable catalytic system. Owing to their reversible switching
      properties in response to external stimuli, these systems are capable of
      improving the mass transports of reactants/products in aqueous solution,
      modulating the chemical reaction rates, and switching the catalytic process on
      and off. Furthermore, their stimuli-responsive properties facilitate the
      separation and recovery of the active catalysts from the reaction mixtures. As a
      fascinating approach of the controllable catalysis, these stimuli-responsive
      catalytic systems including thermoresponsive, pH-responsive, chemo-mechano
      chemical, ionic strength-responsive, and dual-responsive, are reviewed in terms
      of their nanoreactors and mechanisms. 

PMID- 23852652
TI  - Effects of cytochrome P450 inhibitors and inducers on the metabolism and
      pharmacokinetics of ospemifene.
AB  - PURPOSE: The objectives were to determine the cytochrome P450 (CYP) enzymes
      involved in the metabolism of ospemifene and its main hydroxylated metabolites
      and to examine the effects of CYP inhibitors and inducers on ospemifene
      pharmacokinetics. METHODS: In vitro metabolism studies were conducted using human
      liver microsomes; CYP-selective inhibitors and CYP-specific substrates were used
      to determine the roles of nine CYP isoforms in ospemifene metabolism. Two Phase 1
      clinical trials were conducted in healthy postmenopausal women; crossover designs
      examined the effects of pretreatment with the CYP modulators rifampicin,
      ketoconazole, fluconazole and omeprazole on ospemifene pharmacokinetics. RESULTS:
      Although several CYP inhibitors decreased the in vitro formation of ospemifene
      metabolites, none of them completely blocked metabolism. Roles for CYP3A4,
      CYP2C9, CYP2C19 and CYP2B6 in the metabolism of ospemifene and its two main
      metabolites, 4--hydroxyospemifene and 4'-hydroxyospemifene, were confirmed. The
      in vivo experiments demonstrated that ospemifene serum concentrations were
      decreased by rifampicin pretreatment, increased by ketoconazole or fluconazole
      pretreatment, and minimally affected by omeprazole pretreatment. CONCLUSIONS: The
      clinical pharmacokinetic findings and in vitro data suggest that CYP3A4 is
      important for ospemifene metabolism, but other CYP isoforms and metabolic
      pathways also contribute. Strong CYP3A or CYP2C9 inducers (e.g. rifampicin) would
      be expected to decrease the exposure to ospemifene. Ospemifene should be used
      with caution when coadministered with the modest CYP3A inhibitor ketoconazole and
      should not be coadministered with the potent CYP3A/CYP2C9/CYP2C19 inhibitor
      fluconazole. The potent CYP2C19 inhibitor omeprazole is unlikely to cause
      clinically significant changes in ospemifene pharmacokinetics.

PMID- 23852654
TI  - Ultrasound-guided intranodal lymphangiography followed by thoracic duct
      embolization for treatment of postoperative bilateral chylothorax.
AB  - BACKGROUND: Percutaneous thoracic duct embolization (TDE) is a safe, effective,
      and minimally invasive option for treating chylothorax. A recent report
      demonstrated the feasibility of ultrasound-guided intranodal lymphangiography as
      an alternative to pedal lymphangiography for visualization of the thoracic duct,
      promising relative technical ease and decreased procedure time for TDE. METHODS:
      We report a case of postoperative bilateral chylothorax treated with ultrasound
      guided intranodal lymphangiography followed by TDE. RESULTS: Intranodal
      lymphangiography resulted in rapid opacification of the abdominal lymphatics,
      permitting technically successful primary and secondary embolization procedures.
      Deployment of metallic coils and liquid embolic agents within the thoracic duct
      produced rapid clinical and radiographic improvement. CONCLUSION: Intranodal
      lymphangiography is a reliable, reproducible, and less technically challenging
      alternative to pedal lymphangiography.

PMID- 23852655
TI  - MOTOR: model assisted software for NMR structure determination.
AB  - Eukaryotic proteins with important biological function can be partially
      unstructured, conformational flexible, or heterogenic. Crystallization trials
      often fail for such proteins. In NMR spectroscopy, parts of the polypeptide chain
      undergoing dynamics in unfavorable time regimes cannot be observed. De novo NMR
      structure determination is seriously hampered when missing signals lead to an
      incomplete chemical shift assignment resulting in an information content of the
      NOE data insufficient to determine the structure ab initio. We developed a new
      protein structure determination strategy for such cases based on a novel NOE
      assignment strategy utilizing a number of model structures but no explicit
      reference structure as it is used for bootstrapping like algorithms. The software
      distinguishes in detail between consistent and mutually exclusive pairs of
      possible NOE assignments on the basis of different precision levels of measured
      chemical shifts searching for a set of maximum number of consistent NOE
      assignments in agreement with 3D space. Validation of the method using the
      structure of the low molecular-weight-protein tyrosine phosphatase A (MptpA)
      showed robust results utilizing protein structures with 30-45% sequence identity
      and 70% of the chemical shift assignments. About 60% of the resonance assignments
      are sufficient to identify those structural models with highest conformational
      similarity to the real structure. The software was benchmarked by de novo
      solution structures of fibroblast growth factor 21 (FGF21) and the extracellular
      fibroblast growth factor receptor domain FGFR4 D2, which both failed in
      crystallization trials and in classical NMR structure determination.

PMID- 23852656
TI  - Pulmonary complications with the use of mTOR inhibitors in targeted cancer
      therapy: a systematic review and meta-analysis.
AB  - Mammalian target of rapamycin (mTOR) inhibitors have gained regulatory approval
      for use in several cancer types. Pulmonary adverse events associated with mTOR
      inhibitors are well recognized but their frequency has varied considerably among
      trials. PubMed and ASCO abstracts were searched to identify clinical trials of
      mTOR inhibitors in solid tumors. Twenty-two eligible trials on which 4,242
      patients were treated met the criteria for inclusion in this systematic review
      and meta-analysis. Adverse event data were extracted and used to determine the
      incidence rate and incidence rate ratio for pneumonitis, dyspnea, and cough. The
      incidence rate of any grade pneumonitis in patients with solid tumors treated
      with mTOR inhibitors was 0.11 (95% confidence interval (CI), 0.06-0.17) per
      patient, while the incidence of grade 3-4 pneumonitis was 0.03 (95% CI, 0.01
      0.04) per patient. The incidence rate ratio (IRR) of any grade pneumonitis with
      mTOR inhibitors relative to controls was 19.0 (95% CI, 6.5-55.4), and for grade 3
      4 pneumonitis was 8.0 (95% CI, 2.6-24.1). The incidence rate for any grade and
      grade 3-4 cough was 0.23 (95% CI, 0.20-0.27) per patient and 0.01 (95% CI, 0.00
      0.01) per patient, respectively. The incidence rate for any grade and grade 3-4
      dyspnea was 0.15 (95% CI, 0.10-0.21) per patient and 0.03 (95% CI, 0.02-0.04) per
      patient, respectively. Compared to control, treatment with mTOR inhibitors were
      associated with a significant increase in any grade cough [IRR = 1.9 (95% CI, 1.6
      2.4)] and grade 3-4 dyspnea [IRR = 2.0 (95% CI, 1.2-3.3)]. This study provides an
      estimation of the risk of pulmonary adverse events in solid tumor patients
      treated with mTOR inhibitors. While pulmonary adverse events are relatively
      common with mTOR inhibitors, most are low grade and asymptomatic.

PMID- 23852657
TI  - Synthesis of polycyclic aminocyclobutane systems by the rearrangement of N-(ortho
      vinylphenyl) 2-azabicyclo[3.1.0]hexane derivatives.
AB  - The acid-catalysed thermal rearrangements of a family of N-aryl 2
      azabicyclo[3.1.0]hexanes is described. These substrates, designed in such a way
      that the aromatic system is conjugated with an alkene group located at the ortho
      position relative to the nitrogen atom, have been prepared by using an
      intramolecular Kulinkovich-de Meijere reaction. The rearrangements can then be
      conducted either under standard thermal conditions or with microwave activation.
      Depending on the conditions applied and the substitution pattern,
      dihydroquinoline or polycyclic aminocyclobutane derivatives can be obtained. A
      mechanistic discussion is provided, with the proposition of the initial
      protonation of the aminocyclopropane moiety to give an iminium intermediate. By
      analogy with related intermolecular reactions, the involvement of electrocyclic
      reactions among the series of elementary steps that follow is put forward. 

PMID- 23852659
TI  - Cluster headache and oxygen: is it possible to predict which patients will be
      relieved? A prospective cross-sectional correlation study.
AB  - Response to 100 % oxygen as acute treatment for cluster headache is relative low
      considering certain subgroups or predictors. The primary purpose of the present
      study was to find prospectively which factors differ between responders and non
      responders to oxygen therapy. The second goal was to find whether any of these
      differences would clarify the mechanism of pain reduction by oxygen and cluster
      headache pathophysiology. Patients diagnosed with cluster headache according to
      the ICHD-II criteria, who started on oxygen therapy (n = 193), were recruited
      from 51 outpatient clinics and via patient websites in The Netherlands. Patients
      had to return two questionnaires around the start of oxygen therapy (n = 120).
      Eventually, 94 patients were included. Clear non- plus moderate responders had
      ever used pizotifen more often (p = 0.03). Clear non-responders more often had
      photophobia or phonophobia during cluster headache attacks (p = 0.047) and more
      often had used triptans in the same active phase as the phase in which they had
      used oxygen for the first time (p = 0.02). Using correction for multiple testing,
      we could only confirm a statistically significant difference in triptan use. We
      were unable to locate the level of action of oxygen in the thalamus and cortex or
      confirm the sites of its action presently known, solely based on current
      knowledge of photophobia circuits. However, we conclude that particularly the
      higher frequency of photophobia or phonophobia in clear non-responders deserves
      further study to understand the mechanism of pain reduction by oxygen and cluster
      headache pathophysiology.

PMID- 23852658
TI  - Teriflunomide reduces relapse-related neurological sequelae, hospitalizations and
      steroid use.
AB  - Multiple sclerosis (MS) relapses impose a substantial clinical and economic
      burden. Teriflunomide is a new oral disease-modifying therapy approved for the
      treatment of relapsing MS. We evaluated the effects of teriflunomide treatment on
      relapse-related neurological sequelae and healthcare resource use in a post hoc
      analysis of the Phase III TEMSO study. Confirmed relapses associated with
      neurological sequelae [defined by an increase in Expanded Disability Status
      Scale/Functional System (sequelae-EDSS/FS) >= 30 days post relapse or by the
      investigator (sequelae-investigator)] were analyzed in the modified intention-to
      treat population (n = 1086). Relapses requiring hospitalization or intravenous
      (IV) corticosteroids, all hospitalizations, emergency medical facility visits
      (EMFV), and hospitalized nights for relapse were also assessed. Annualized rates
      were derived using a Poisson model with treatment, baseline EDSS strata, and
      region as covariates. Risks of sequelae and hospitalization per relapse were
      calculated as percentages and groups were compared with a chi(2) test. Compared
      with placebo, teriflunomide reduced annualized rates of relapses with sequelae
      EDSS/FS [7 mg by 32 % (p = 0.0019); 14 mg by 36 % (p = 0.0011)] and sequelae
      investigator [25 % (p = 0.071); 53 % (p < 0.0001)], relapses leading to
      hospitalization [36 % (p = 0.015); 59 % (p < 0.0001)], and relapses requiring IV
      corticosteroids [29 % (p = 0.001); 34 % (p = 0.0003)]. Teriflunomide-treated
      patients spent fewer nights in hospital for relapse (p < 0.01). Teriflunomide 14
      mg also decreased annualized rates of all hospitalizations (p = 0.01) and EMFV (p
      = 0.004). The impact of teriflunomide on relapse-related neurological sequelae
      and relapses requiring healthcare resources may translate into reduced healthcare
      costs.

PMID- 23852660
TI  - No evidence for CCVSI in relapsing-remitting multiple sclerosis patients with
      moderate disability.

PMID- 23852661
TI  - Intralesional autologous mesenchymal stem cells in management of osteonecrosis of
      femur: a preliminary study.
AB  - BACKGROUND: Management of early stages of osteonecrosis aims to prevent the
      collapse of the femoral head by attempts at restoring the vascularity of femoral
      head. Bone marrow-derived mononuclear cells with their angiogenic and osteogenic
      properties appear to have the potential to halt the disease process when injected
      intralesionally following core decompression. MATERIALS AND METHODS: Forty
      patients (60 hips) with stage I, II or III (ARCO system) osteonecrosis of femoral
      head were treated by either core decompression and isolated mononuclear cells
      (group A) or core decompression and unprocessed bone marrow injection (group B).
      The patients were followed up clinically and radiologically for a minimum of 2
      years. The functional outcome was assessed in terms of Harris hip score, and
      disease progression was assessed radiologically by comparing the preoperative and
      follow-up MRI at the end of 2 years. RESULTS: On 2-year follow-up, there was
      considerable improvement in the hip function as measured by the Harris hip score
      in both the groups (p = 0.031). On MRI, there was a decrease in the size of the
      lesion in group A (p = 0.03). Three of 30 hips (10.0 %) in group B required total
      hip replacement. CONCLUSIONS: Implantation of autologous bone marrow stem cells
      in avascular necrosis of femoral head is a safe and effective procedure and has
      better outcome than bone marrow for early stage of avascular necrosis of femoral
      head.

PMID- 23852663
TI  - Liver transplantation for hepatitis B liver disease and concomitant
      hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and
      nucleoside/nucleotide analogues.
AB  - Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may
      favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy
      with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may
      reduce HBV recurrence after LT. To test associations between HBV, HCC, and
      survival, we performed a retrospective chart review of patients undergoing LT for
      HBV between January 1985 and December 2010 at 7 US transplant centers. After we
      divided the patients into 3 eras based on evolving strategies in antiviral
      therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to
      determine whether there were associations between survival and HCC recurrence.
      Seven hundred thirty-eight patients underwent transplantation for HBV, and 354
      (48.0%) had concomitant HCC, which recurred in 58 patients (16.4%). Three-year
      survival was much better in era 3 versus era 1 (87% versus 40%, P = 0.001), and
      the incidence of HCC recurrence was lower (12% versus 29%, P = 0.009). The lungs
      were the most frequent first site of HCC recurrence, and they were followed by
      the liver. A multivariate analysis showed that HBV reinfection, HCC recurrence,
      and HBIG use were associated with worse survival (P < 0.001, P < 0.001, and P =
      0.002, respectively); HCC recurrence and stage 3 HCC, among other factors, were
      associated with HBV reinfection (P < 0.001 and P = 0.004); and stage 3 HCC,
      vascular invasion of the explanted tumor, and post-LT chemotherapy were
      associated with HCC recurrence (P = 0.008, P < 0.001, and P < 0.001,
      respectively). Patients with HBV reinfection were 3.6 times more likely than
      patients without HBV to have HCC recurrence. These data suggest further study of
      attempts at LT for patients with HBV and HCC beyond the Milan criteria if their
      HBV is aggressively and successfully treated.

PMID- 23852662
TI  - Rivaroxaban is as efficient and safe as bemiparin as thromboprophylaxis in knee
      arthroscopy.
AB  - PURPOSE: The aim of this study is to compare effectiveness and safety profile of
      rivaroxaban with bemiparin in 3-week extended prophylaxis after knee arthroscopy.
      METHODS: Four hundred and sixty-seven patients were included in this review
      divided in two groups. One followed prophylaxis with rivaroxaban and the other
      one with bemiparin. All patients were interviewed and explored at 1 and 3 months
      postoperatively, looking for symptomatic signs of deep-vein thrombosis (DVT). In
      case of suspicion, diagnostic tests were performed. Collected data were age, sex,
      gender, diagnosis, time with ischemia, body mass index, concomitant diseases,
      concomitant therapy, DVT signs, treatment satisfaction, minor and major
      complications, treatment adherence and tolerability. RESULTS: No thromboembolic
      events were observed in any of the groups. In one case treated with rivaroxaban,
      the drug had to be withdrawn due to epistaxis. CONCLUSIONS: Our study showed that
      extended prophylaxis with 10 mg of rivaroxaban once daily for 3 weeks resulted as
      effective as bemiparin in knee arthroscopy thromboprophylaxis.

PMID- 23852664
TI  - In vitro induction of potent tumor-specific cytotoxic T lymphocytes using TLR
      agonist-activated AML-DC.
AB  - Dendritic cells (DCs) are recognized as key regulators of the immune system.
      Active DC immunization protocols are quickly obtaining interest as an alternative
      therapeutic approach in acute myeloid leukemia patients. Despite apparent
      progress in DC-based immunotherapy, some discrepancies were reported in
      generating potent DCs and their source. In addition to monocytes, DCs can be
      differentiated from leukemic blasts of acute myeloid leukemia (AML) patients (AML
      DC) possessing the ability of stimulating anti-leukemic immune response. In this
      study, we differentiated peripheral blood blasts of 16 out of 20 AML patients in
      vitro in the presence of GM-CSF and IL-4 into immature AML-DC. Then, DCs matured
      using different combinations of Toll-like receptor (TLR) ligands to obtain
      functional DCs as demonstrated by cell morphology, immunophenotype, and
      functional activity. Autologous cytotoxic T cell induction of matured DCs was
      evaluated in four patients and compared with immature counterparts. Our results
      showed that although the TLR3 agonist (Poly I:C) has a synergistic effect on the
      TLR4 agonist (lipopolysaccharide, LPS), the addition of the TLR7/8 agonist (R848)
      is necessary to reinforce the effect of LPS or LPS + POLY(I:C) to produce
      efficient DCs with the higher level of IL-12 (30 to 90 times). Such DCs activate
      allogeneic T cells and effectively prime autologous cytotoxic T cells in vitro.
      In contrast, FSL-1 as a TLR2/6 agonist has a negative effect on LPS + Poly(I:C)
      and LPS + R848 to produce IL-12. Thus, DCs prepared using a maturation mixture
      including a TLR7/8 agonist may be used as a potential tool for DC-based
      immunotherapy purposes in leukemic patients. 

PMID- 23852665
TI  - The success story of trastuzumab emtansine, a targeted therapy in HER2-positive
      breast cancer.
AB  - Trastuzumab emtansine is a unique antibody-drug conjugate targeting selectively
      human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells,
      thus conferring high efficacy with minimal systemic toxicities. Trastuzumab
      emtansine consists of a monoclonal antibody trastuzumab and potent cytotoxic
      agent DM1, combined together through a stable thioether bond. First-in-man phase
      I study set the maximum tolerated dose at 3.6 mg/kg given intravenously on a 3
      weekly regimen. In phase II studies, trastuzumab emtansine at 3.6 mg/kg provided
      objective tumour responses and clinical benefit with an encouraging safety
      profile. Over these studies, trastuzumab emtansine had favourable
      pharmacokinetics. No accumulation of trastuzumab emtansine or catabolites was
      observed even after repeated dosing and free DM1 was very low in circulation. The
      stability of trastuzumab emtansine in circulation justifies the minimal systemic
      toxicity observed. Recently, a randomised international open-label phase III
      study confirmed the efficacy and safety of trastuzumab emtansine versus lapatinib
      plus capecitabine in patients with HER2-positive locally advanced or metastatic
      breast cancer. Overall survival was significantly improved in the trastuzumab
      emtansine arm. Safety outcomes were also favourable. The adverse events
      traditionally related to chemotherapy were markedly lower or absent with
      trastuzumab emtansine. Cardiotoxicity, frequently observed in HER2-directed
      therapy, was not reported. Although thrombocytopenia and elevations in hepatic
      enzymes were reported with trastuzumab emtansine, these events were reversible
      and manageable. Ongoing trials investigating trastuzumab emtansine as a single
      agent or in combination with other agents, will determine the place of
      trastuzumab emtansine in the current therapeutic strategies deployed for HER2
      metastatic breast cancer.

PMID- 23852666
TI  - Crystal structure of a member of a novel family of dioxygenases (PF10014) reveals
      a conserved cupin fold and active site.
AB  - PF10014 is a novel family of 2-oxyglutarate-Fe(2+) -dependent dioxygenases that
      are involved in biosynthesis of antibiotics and regulation of biofilm formation,
      likely by catalyzing hydroxylation of free amino acids or other related ligands.
      The crystal structure of a PF10014 member from Methylibium petroleiphilum at 1.9
      A resolution shows strong structural similarity to cupin dioxygenases in overall
      fold and active site, despite very remote homology. However, one of the beta
      strands of the cupin catalytic core is replaced by a loop that displays
      conformational isomerism that likely regulates the active site.

PMID- 23852668
TI  - Ultrasensitive telomerase activity detection by telomeric elongation controlled
      surface enhanced Raman scattering.
AB  - Telomerase is now considered to be a valuable biomarker and therapeutic target in
      the diagnosis and treatment of cancerous diseases, which brings an urgent need in
      the development of fast and efficient telomerase detection strategies. Here, a
      new surface enhanced Raman scattering (SERS) based protocol using telomeric
      elongation controlled SERS (TEC-SERS) effect for the ultrasensitive telomerase
      detection is presented. The TEC-SERS protocol not only provides an unprecedented
      high sensitivity but also avoids laborious PCR procedures. The detection limit is
      ~2-3 orders of magnitude lower than those of previously reported methods. This
      highly sensitive and straightforward TEC-SERS protocol can be developed as a
      routine telomerase detection method, which would greatly facilitate the
      telomerase based ultra-early diagnosis of malignant tumors and the fast screening
      of anti-cancer drugs. 

PMID- 23852669
TI  - Redox-switchable ring-closing metathesis: catalyst design, synthesis, and study.
AB  - High yielding syntheses of 1-(ferrocenylmethyl)-3-mesitylimidazolium iodide (1)
      and 1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene (2) were developed.
      Complexation of 2 to [{Ir(cod)Cl}2] (cod=cis,cis-1,5-cyclooctadiene) or
      [Ru(PCy3)Cl2(=CH-o-O-iPrC6H4)] (Cy=cyclohexyl) afforded 3 ([Ir(2)(cod)Cl]) and 5
      ([Ru(2)Cl2(=CH-o-O-iPrC6H4)]), respectively. Complex 4 ([Ir(2)(CO)2Cl]) was
      obtained by bubbling carbon monoxide through a solution of 3 in CH2Cl2.
      Spectroelectrochemical IR analysis of 4 revealed that the oxidation of the
      ferrocene moiety in 2 significantly reduced the electron-donating ability of the
      N-heterocyclic carbene ligand (DeltaTEP=9 cm(-1); TEP=Tolman electronic
      parameter). The oxidation of 5 with [Fe(eta(5)-C5H4COMe)Cp][BF4] as well as the
      subsequent reduction of the corresponding product [5][BF4] with
      decamethylferrocene (Fc*) each proceeded in greater than 95% yield. Mossbauer,
      UV/Vis and EPR spectroscopy analysis confirmed that [5][BF4] contained a
      ferrocenium species, indicating that the iron center was selectively oxidized
      over the ruthenium center. Complexes 5 and [5][BF4] were found to catalyze the
      ring-closing metathesis (RCM) of diethyl diallylmalonate with observed pseudo
      first-order rate constants (k(obs)) of 3.1*10(-4) and 1.2*10(-5) s(-1),
      respectively. By adding suitable oxidants or reductants over the course of a RCM
      reaction, complex 5 was switched between different states of catalytic activity.
      A second-generation N-heterocyclic carbene that featured a 1',2',3',4',5'-
      pentamethylferrocenyl moiety (10) was also prepared and metal complexes
      containing this ligand were found to undergo iron-centered oxidations at lower
      potentials than analogous complexes supported by 2 (0.30-0.36 V vs. 0.56-0.62 V,
      respectively). Redox switching experiments using [Ru(10)Cl2(=CH-o-O-iPrC6H4)]
      revealed that greater than 94% of the initial catalytic activity was restored
      after an oxidation-reduction cycle.

PMID- 23852667
TI  - Mathematical modeling of kidney transport.
AB  - In addition to metabolic waste and toxin excretion, the kidney also plays an
      indispensable role in regulating the balance of water, electrolytes, nitrogen,
      and acid-base. In this review, we describe representative mathematical models
      that have been developed to better understand kidney physiology and
      pathophysiology, including the regulation of glomerular filtration, the
      regulation of renal blood flow by means of the tubuloglomerular feedback
      mechanisms and of the myogenic mechanism, the urine concentrating mechanism,
      epithelial transport, and regulation of renal oxygen transport. We discuss the
      extent to which these modeling efforts have expanded our understanding of renal
      function in both health and disease.

PMID- 23852670
TI  - Toxicities and costs of placing prophylactic and reactive percutaneous
      gastrostomy tubes in patients with locally advanced head and neck cancers treated
      with chemoradiotherapy.
AB  - BACKGROUND: We compared dependence rates, complications, toxicities, and costs
      associated with prophylactic versus reactive percutaneous endoscopic gastrostomy
      (PEG) tube placement. METHODS: One hundred ninety-three patients with locally
      advanced head and neck squamous cell carcinoma treated with concurrent
      chemoradiotherapy were retrospectively reviewed. RESULTS: The 1-year and 2-year
      actuarial PEG tube dependence rate of the entire cohort was 24% and 13%,
      respectively. There was no difference in the PEG tube dependence rates between
      those placed prophylactically versus reactively. Patients who received a PEG tube
      reactively had a significantly higher stricture rate (p = .03) and aspiration
      rate (p < .001) compared to the prophylactic group. There were significantly
      fewer hospitalizations in the prophylactic group compared to the reactive group
      (p = .003). When accounting for both PEG placement and hospitalizations, the
      prophylactic approach was found to be more cost effective. CONCLUSION: PEG tubes
      placed prophylactically were associated with lower rates of strictures,
      aspirations, hospitalizations, and costs compared to those placed reactively.

PMID- 23852671
TI  - Eugenol enhances the resistance of tomato against tomato yellow leaf curl virus.
AB  - BACKGROUND: Tomato yellow leaf curl virus disease (TYLCVD) causes severe to
      economic losses in tomato crops in China. The control of TYLCVD is based
      primarily on the use of synthetic insecticide to control its vector whitefly
      (Bemisia tabaci). To look for an alternative method for disease control, we
      investigated the effect of eugenol on controlling TYLCVD. The potential of
      eugenol to trigger systemic acquired resistance (SAR) in tomato (Jiangsu 14)
      plants against TYLCV was also investigated. RESULTS: In greenhouse experiments,
      eugenol significantly reduced disease severity when applied as a foliar spray,
      thus demonstrating a systemic effect. The disease spread rapidly in control
      plants and by the end of the experiment almost all control plants showed severe
      symptoms. Eugenol also induced H2O2 accumulation in tomato plants. Activities of
      peroxidase (POD), polyphenol oxidase (PPO) and phenylalanine ammonia lyase (PAL)
      were significantly induced compared with those of control plants. As further
      consequences, increase of salicylic acid (SA) levels and expression of PR-1
      proteins, a molecular marker of SAR in tomato, could also be observed.
      CONCLUSION: This is the first report of eugenol as an elicitor and its ability to
      suppress plant virus diseases under greenhouse conditions. It is suggested that
      eugenol has the potential to be an effective biocontrol agent against TYLCV in
      tomato plants.

PMID- 23852672
TI  - Global optimization of parameters in the reactive force field ReaxFF for SiOH.
AB  - We have used unbiased global optimization to fit a reactive force field to a
      given set of reference data. Specifically, we have employed genetic algorithms
      (GA) to fit ReaxFF to SiOH data, using an in-house GA code that is parallelized
      across reference data items via the message-passing interface (MPI). Details of
      GA tuning turn-ed out to be far less important for global optimization efficiency
      than using suitable ranges within which the parameters are varied. To establish
      these ranges, either prior knowledge can be used or successive stages of GA
      optimizations, each building upon the best parameter vectors and ranges found in
      the previous stage. We have finally arrive-ed at optimized force fields with
      smaller error measures than those published previously. Hence, this optimization
      approach will contribute to converting force-field fitting from a specialist task
      to an everyday commodity, even for the more difficult case of reactive force
      fields.

PMID- 23852673
TI  - A review of integrating electroactive polymers as responsive systems for
      specialized drug delivery applications.
AB  - Electroactive polymers (EAPs) are promising candidate materials for the design of
      drug delivery technologies, especially in conditions where an "on-off" drug
      release mechanism is required. To achieve this, EAPs such as polyaniline,
      polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene may be
      blended into responsive hydrogels in conjunction with the desired drug to obtain
      a patient-controlled drug release system. The "on-off" drug release mechanism can
      be achieved through the environmental-responsive nature of the interpenetrating
      hydrogel-EAP complex via (i) charged ions initiated diffusion of drug molecules;
      (ii) conformational changes that occur during redox switching of EAPs; or (iii)
      electroerosion. These release mechanisms are not exhaustive and new release
      mechanisms are still under investigation. Therefore, this review seeks to provide
      a concise incursion and critical overview of EAPs and responsive hydrogels as a
      strategy for advanced drug delivery, for example, controlled release of
      neurotransmitters, sulfosalicyclic acid from cross-linked hydrogel, and vaccine
      delivery. The review further discusses techniques such as linear sweep
      voltammetry, cyclic voltammetry, impedance spectroscopy, and chronoamperometry
      for the determination of the redox capability of EAPs. The future implications of
      the hydrogel-EAP composites include, but not limited to, application toward
      biosensors, DNA hybridizations, microsurgical tools, and miniature bioreactors
      and may be utilized to their full potential in the form of injectable devices as
      nanorobots or nanobiosensors.

PMID- 23852674
TI  - The rate of energy dissipation determines probabilities of non-equilibrium
      assemblies.

PMID- 23852675
TI  - Coinfection of hepatitis B and hepatitis delta virus in Belgium: a multicenter
      BASL study. Prospective epidemiology and comparison with HBV mono-infection.
AB  - Epidemiological data on hepatitis delta virus (HDV) infection in Belgium are
      lacking. A multicenter questionnaire-based registry on HDV infection was collated
      between March 1, 2008 and February 28, 2009. It consisted of patients coinfected
      with hepatitis B virus (HBV) and HDV. The data samples were compared to those of
      a concurrent registry on HBV infection. Prospective data of patients with HBV-HDV
      coinfection were collected. Active HBV replication is defined as HBeAg positivity
      or HBV DNA > 2,000 IU/ml. Forty-four patients from 15 centers were registered. A
      comparison of 29 patients infected with HDV (registered in the concurrent HBV
      registry) was made against 785 HBV mono-infected patients. The seroprevalence of
      patients coinfected with HBV and HDV in Belgium is reported to be 3.7% (29/785),
      consisting solely of the HBV-HDV coinfected patients in the HBV registry. This
      rises to 5.5% (44/800) if all patients infected with HDV from the two registries
      combined are included. The patients coinfected with HBV and HDV had higher (P <
      0.05) ALT values and more advanced liver disease (Metavir score >=F2), but had
      less active HBV replication and lower HBV DNA titers when compared with the
      patients infected only with HBV. Additionally, the majority of HBV-HDV coinfected
      patient was male, and 13.6% (6/44) of the patients that were coinfected HBV and
      HDV were also infected with HCV. In conclusion, this study provided much needed
      epidemiological data on the current state of HDV infection in Belgium.

PMID- 23852676
TI  - Long-term efficacy of the hepatitis B vaccine in a high-risk group.
AB  - Chronic infection with hepatitis B virus (HBV) is a global health problem. In an
      attempt to control infection, worldwide HBV vaccination programs have been
      established. Saudi Arabia, an endemic area for HBV infection, established an HBV
      immunization program in 1989. This cross-sectional study evaluates the long-term
      protection of HBV vaccination 14-24 years after primary immunization in a high
      risk group (clinical year medical students) at King Abdulaziz University Hospital
      in Jeddah, Saudi Arabia. All participants had complete HBV immunization at birth
      or in early childhood. Hepatitis B surface antibody (anti-HBs) levels were
      obtained. An anti-HBs titer of <10 mIU/ml indicated no protection, while a titer
      of >10 mIU/ml was considered to represent protective immune status. A total of
      238 students were included; they were predominantly females (n = 182, 76.5%).
      Mean age was 22.2 +/- 1.1 years. Duration since primary vaccination was 19.8 +/-
      2.3 years. Female students were more likely to maintain long-term protection
      compared to males (62.1% and 58.8%, respectively). Anti-HBs levels were
      significantly low in many students after primary immunization. Testing medical
      students for anti-HBs levels may be warranted as they represent a high-risk
      population. The higher rate of vaccine failure in males than females requires
      further investigation as it may explain the higher prevalence of HBV in the male
      population.

PMID- 23852677
TI  - Vitamin D status and serum ferritin concentration in chronic hepatitis C virus
      type 1 infection.
AB  - The circulating 25-hydroxylated form of vitamin D(3), 25(OH)D, and serum ferritin
      concentrations have been described to be associated with disease progression in
      chronic hepatitis C. Both parameters also have been assessed with regard to
      treatment outcome, however, with divergent results. This study examined both the
      pre- and posttreatment serum concentrations of 25(OH)D and ferritin in 191
      patients infected chronically with hepatitis C virus (HCV) type 1 with regard to
      liver inflammatory activity (grading), disease progression in terms of fibrosis
      (staging) and an antiviral treatment outcome. Mean pretreatment serum 25(OH)D and
      ferritin concentrations were 18 +/- 10 ng/ml and 280 +/- 225 ug/L, respectively.
      Multivariate analysis revealed lower pretreatment serum 25(OH)D and higher
      ferritin concentrations to be significantly related to both severity of
      inflammatory activity and of fibrotic alterations. Pretreatment serum ferritin
      concentration, furthermore, unlike 25(OH)D concentration, was found to be
      associated with a sustained virological response by uni- and multivariate
      analyses. A sustained virological response was featured by a significant increase
      in serum 25(OH)D levels (18 +/- 10 ng/ml vs. 22 +/- 11 ng/ml; P < 0.01), a
      reduction of serum ferritin concentration (191 +/- 156 ug/L vs. 103 +/- 63 ug/L;
      P < 0.001) and a normalization of serum alanine aminotransferase (ALT) and gamma
      glutamyl-transferase (gamma-GT) activities. Taken together, decreased 25(OH)D and
      increased ferritin serum levels indicate the severity of hepatic inflammation and
      fibrosis in patients infected chronically with HCV type 1. Elevated ferritin,
      furthermore, was found to be an independent predictor for standard IFN-based
      therapy responsiveness.

PMID- 23852678
TI  - The prevalence of neutralizing antibodies against AAV serotype 1 in healthy
      subjects in China: implications for gene therapy and vaccines using AAV1 vector.
AB  - Recombinant adeno-associated virus serotype 1 (AAV1) has attracted tremendous
      interest as a promising vector for gene therapy and vaccine applications.
      However, the presence of AAV1 neutralizing antibodies as a consequence of
      exposure to wild type AAV1 can limit significantly effective gene transfer for
      biologics based AAV1 vector. Prior studies have reported that a prevalence of
      AAV1 neutralizing antibodies ranged from 10% to 50% in different countries around
      the world, and up to 79% in Dutch subjects. However, few studies have reported on
      the AAV1 neutralizing antibody prevalence in Chinese subjects. In this study, a
      high-throughput luciferase-based virus neutralization assay was established and
      standardized for critical parameters, including the appropriate cell line, and
      the optimal viral infection dose, and the infection time with homologous AAV1
      vaccinated mice and guinea pig sera. Then, a total of 500 healthy individual
      serum samples from two separate regions of China were screened for the AAV1
      neutralizing antibodies by conducting a non-randomized, cross-sectional analysis.
      Interestingly, a high prevalence of AAV1 neutralizing antibody (69.8%) was found
      in all individuals. There was significant difference observed for prevalence by
      gender (P = 0.042), age range (P = 0.011) and geographic origin (P < 0.001). The
      percentage of positive AAV1 neutralizing antibodies (NT50  > 10) in teenagers
      (year <18, as of 2012) was significant lower than that of adults (19-56, as of
      2012) (P = 0.011), indicating the optimal vaccination period of childhood. The
      current study provides a useful insight for the future development of AAV1-based
      vaccination and gene therapy strategies in Beijing and Anhui provinces of China.

PMID- 23852679
TI  - Impact of human cytomegalovirus (CMV) infection on immune response to pandemic
      2009 H1N1 influenza vaccine in healthy adults.
AB  - Human cytomegalovirus (CMV) infection has been implicated in immunosenescence. To
      examine the influence of CMV on ability of healthy adults to respond to a novel
      influenza antigen, the rate of seroconversion and the magnitude of titers to
      pandemic 2009 H1N1 vaccine was assessed. The clinical trial was stratified by
      age; 52 persons aged 18-64 and 55 aged 65 and older were enrolled. Among the
      younger group, 33% had CMV antibody compared with 62% among the older group. No
      differences by CMV seropositivity in the proportion of participants achieving a
      seroprotective titer 21 days following the second immunization were noted.
      However, the geometric mean titer in hemagglutination inhibition assay was
      significantly higher among CMV seronegative younger participants compared with
      CMV seropositive younger participants (385 vs. 142, P = 0.013). In contrast,
      among the older group, CMV serostatus was not associated with differential
      antibody titers (53 vs. 63, P = 0.75). These data suggest that CMV may shape
      immune response to neoantigens among younger persons; these groups should be
      included in future studies of immunosenescence and CMV.

PMID- 23852680
TI  - Concordance of human papillomavirus types detected on the surface and in the
      tissue of genital lesions in men.
AB  - Swabbing the surface of a genital lesion to obtain a sample for HPV DNA testing
      is less invasive than a biopsy, but may not represent HPV types present in the
      lesion tissue. The objective of this study was to examine the concordance of HPV
      types detected in swab and biopsy samples from 165 genital lesions from men ages
      18-70. Lesions included 90 condyloma, 10 penile intraepithelial neoplasia (PeIN),
      23 non-condyloma with a known histology, and 42 lesions with an undetermined
      histology. All lesions were sampled by swabbing the surface of the lesion with a
      pre-wetted Dacron swab and taking a shave biopsy. HPV genotyping was performed
      using Linear Array for swab samples and INNO-LiPA for biopsy samples. The kappa
      and McNemar statistics were used to compare the concordance of detecting HPV
      types in swab and biopsy samples. Both sampling methods had high agreement for
      detection of HPV DNA in condyloma (87.8% agreement) and PeIN (100% agreement).
      There was also high concordance for detection of HPV16 (kappa = 1.00) and HPV18
      (kappa = 1.00) in PeIN, however, agreement was low to moderate for detecting HPV6
      (kappa = 0.31) and HPV11 (kappa = 0.56) in condyloma. Low to moderate agreement
      was also observed between sampling methods for detecting individual HPV types in
      the non-condyloma and lesions with an indefinite histology. The results suggest
      that obtaining a biopsy in addition to swabbing the surface of a lesion may
      provide additional information about specific HVP types associated with male
      genital lesions.

PMID- 23852681
TI  - Intratypic variants of human papillomavirus type 16 and risk of cervical
      neoplasia in Taiwan.
AB  - The associations between variants of human papillomavirus (HPV) 16 and risk of
      cervical neoplasia have been reported, but nucleotide variations of HPV 16 in
      Asian populations and their association with cervical neoplasia have not been
      evaluated extensively. During 1991-1992, 11,923 women from seven townships in
      Taiwan were enrolled. The HPV DNA in cervical cells was detected and genotyped
      using EasyChip HPV blot. Nucleotide variations in the long control region (LCR),
      E6, and E7 genes were determined using DNA sequencing for 170 HPV 16-positive
      cervical samples. The Asian variant was the most prevalent variant (81.8%) of HPV
      16 in Taiwan, and was also associated with increased prevalence of histologically
      confirmed cervical intraepithelial neoplasia grade 3 or worse, showing an age
      adjusted odds ratio (exact confidence limits) of 10.70 (1.62-451.05; P = 0.0049)
      compared to the HPV 16 European variant. Similar significant associations with
      cervical intraepithelial neoplasia grade 3 or worse were also observed for
      distinct nucleotide substitutions, including T178A/G, A647G, A7730C/G, T7781C,
      G7842A, and C24T/G. These results demonstrate that non-European variants (non-E)
      of HPV 16, predominantly Asian variants, are associated with increased risk for
      severe cervical neoplasia, compared with European variants. Molecular mechanisms
      accounting for varied cervical neoplasia risk among different HPV 16 variants
      warrant further investigation.

PMID- 23852682
TI  - Prevalence of human papillomavirus infection in women in some cities and regions
      of Bulgaria.
AB  - This aim of this study was to evaluate the prevalence of human papillomavirus
      (HPV) infections among women (aged 15-55 years) in four of the biggest cities and
      regions in Bulgaria (viz., Sofia, Plovdiv, Varna, and Burgas), as well as in two
      other smaller cities (viz., Pleven and Vidin). Furthermore, study aimed to
      identify the prevalence of the 12 high-risk HPV (HR-HPV) genotypes in 2012, and
      to predict the benefits of a future national vaccination campaign for 12-year-old
      girls in Bulgaria. This HPV genotypes prevalence study covered 2,331,341 women
      from these cities and regions, representing 61.7% of the female population of
      Bulgaria. DNA-sorb-AM nucleic acid extraction kit was used to analyze the HPV
      status in cervical samples collected during a 4-year period (2008-2011) from
      1,120 women aged 15-55 years (divided into four age groups) who had visited 47
      gynecological clinics across the study sites. HR-HPV infections were confirmed in
      435 (38.8%) of the women examined. The remaining 685 (61.2%) women were found to
      be HR-HPV negative. The most common genotype in all 435 infected women was HPV16,
      which was found in 200 women (46%), followed by HPV56 in 86 women (19.8%), HPV31
      in 53 women (12.2%), and HPV33 in 50 women (11.5%). This is the first study to
      have established the prevalence of HR-HPV infections in the larger Bulgarian
      regions and cities (including the capital), and to have drawn attention to the
      unusually high proportion of the different HR-HPV genotypes.

PMID- 23852683
TI  - Environmental impact and seroepidemiology of HTLV in two communities in the
      eastern Brazilian amazon.
AB  - The objective of this study was to detect antibodies for human T lymphotropic
      virus (HTLV) in subjects residing in two communities located in the eastern
      Brazilian Amazon and on the shores of the Tucurui hydroelectric power plant. A
      total of 657 serum samples were analysed using an enzyme-linked immunosorbent
      assay with an anti-HTLV antibody (SymbiosisTM, Sao Paulo, Brazil), demonstrating
      a virus prevalence of 4.7%. Most individuals with HTLV were aged over 30 years (P
      = 0.013), were unmarried (P = 0.019), resided in the area for more than 10 years
      (P = 0.001), had a low level of education (P = 0.015), and had a family income of
      up to $305 (100%). In contrast, there was no significant association between
      infection and sex, city of birth, haemotransfusion, or previous surgery. The
      prevalence observed in these communities suggests that the residents should be
      concerned about HTLV infection, and that some areas may become endemic for HTLV.

PMID- 23852684
TI  - Long-term and cross-reactive immunogenicity of inactivated trivalent influenza
      vaccine in the elderly: MF59-adjuvanted vaccine versus unadjuvanted vaccine.
AB  - Elderly people are at great risk for influenza-related serious complications.
      However, influenza vaccine-induced antibodies are believed to decline more
      rapidly in the elderly. This study was designed to evaluate the long-term and
      cross-reactive immunogenicity among those aged >=65 years for two seasonal
      trivalent influenza vaccines during the 2009-2010 influenza season. One vaccine
      had the MF59 adjuvant, while the other did not contain an adjuvant. Serum
      hemagglutinin inhibition (HI) titers were determined pre-vaccination and at 1 and
      6 months post-vaccination. Of the 100 subjects, 95 (95%) were followed-up for 1
      month after vaccination, and 76 (76%) were followed-up for 6 months after
      vaccination. Both vaccines met the European Medicines Agency (EMA) criteria 1
      month after vaccination. However, seroprotection for influenza B was not
      satisfactory, with a rate of 55.3% for the MF59 adjuvant vaccine and 47.9% for
      the vaccine without adjuvant. At 6 months post-vaccination, the MF59-adjuvanted
      vaccine showed a higher seroprotection rate than the unadjuvanted vaccine. At
      this point, the MF59-adjuvanated vaccine still met the criteria of EMA for A/H1N1
      (62.5% vs. 55.5%, P = 0.64) and A/H3N2 (72.5% vs. 47.2%, P = 0.04). Both vaccines
      showed excellent cross-reactive immunogenicity for influenza A/Solomon
      Island/3/2006 (H1N1) and A/Wisconsin/67/2005 (H3N2), without significant
      differences. In comparison, cross-reactive immunogenicity was not remarkable for
      the A/California/7/2009 (H1N1) and A/New Caledonia/20/1999 (H1N1) strains, which
      have a greater antigenic distance. In conclusion, the MF59-adjuvanted influenza
      vaccine showed superior long-term immunogenicity in the elderly compared to the
      unadjuvanted vaccine. However, cross-reactive immunogenicity was not remarkably
      enhanced with the MF59 adjuvant.

PMID- 23852685
TI  - Evaluation of the automated multianalyte point-of-care mariPOC(r) test for the
      detection of influenza A virus and respiratory syncytial virus.
AB  - The aim of the study was to evaluate the performance of the new mariPOC((r))
      method against the direct fluorescent antibody assay (DFA) as the primary
      reference method for rapid virus detection from nasopharyngeal aspirates and swab
      samples. The study was an open prospective evaluation during the seasonal winter
      epidemics in the Mikkeli Central Hospital, Finland. Altogether, 283 samples were
      analyzed; 124 (43.8%) were from young children (<5 years old). Discrepant samples
      were resolved by PCR. With nasopharyngeal aspirate samples, the sensitivity and
      clinical specificity of the mariPOC((r)) assay for influenza A virus and
      respiratory syncytial virus, were 85.7% (CI 69.7-95.2) and 90% (CI 52.0-80.5),
      and 100% and 99.5%, respectively. The mariPOC((r)) performed less well with swab
      samples having sensitivities at 77.3% (CI 54.6-92.2) and 67.4% (CI 52-80.5),
      respectively. The specificities were as for nasopharyngeal aspirates.
      Importantly, similar performance was observed regardless of the cohort age group.
      In conclusion, the mariPOC((r)) test system has a high potential and utility in
      duty units because it is fast, simple, and multianalyte. The importance of
      personnel training for proper sample collection should be emphasized.

PMID- 23852686
TI  - Population-based assessment of kaposi sarcoma-associated herpesvirus DNA in
      plasma among Ugandans.
AB  - Risk of Kaposi sarcoma (KS) is linked to detection of Kaposi sarcoma-associated
      herpesvirus (KSHV) DNA in plasma, but little is known about the prevalence and
      risk factors for plasma KSHV DNA detection among the general population where KS
      is endemic. Correlates of KSHV plasma detection were investigated in a population
      based sample of adult Ugandans (15-59 years) who participated in an HIV/AIDS
      serobehavioral survey in 2004/2005. KSHV DNA was measured in plasma of 1,080 KSHV
      seropositive and 356 KSHV seronegative persons using polymerase chain reaction
      (PCR). KSHV DNA in plasma was detected in 157 (8.7%) persons; of these 149 (95%)
      were KSHV seropositive and 8 (5%) were seronegative. Detection of KSHV DNA in
      plasma was significantly associated with male sex (P < 0.001), older age (P =
      0.003), residence in a rural versus urban area (P = 0.002), geographic region (P
      = 0.02), and being KSHV seropositive (13.8% seropositive vs. 2.3% seronegative, P
      < 0.001). In a multivariable model, KSHV DNA plasma quantity was significantly
      higher in men (P = 0.002), inversely associated with age (P = 0.05), and residing
      in an urban area (P = 0.01). In Uganda, KSHV is detected more frequently in the
      plasma of adult males and residents of rural regions, potentially explaining the
      increased risk of KS in these subsets of the Ugandan population.

PMID- 23852687
TI  - Different norovirus genotypes in patients with gastroenteritis in Kuwait.
AB  - Norovirus is a leading cause of acute gastroenteritis worldwide. The importance
      of this virus infection in Kuwait is not known. Eight out of 100 stool samples
      (8.0%) from children up to 5 years of age with gastroenteritis studied during
      2006-2007 from one hospital, and 6 out of 70 stool samples (8.5%) from similar
      children studied from another hospital during 2010-2011 were positive for
      norovirus by RT-PCR. Out of these 170 samples studied from both hospitals, 10
      samples were positive for norovirus when tested by ELISA. Phylogenetic tree
      analysis of norovirus strains showed that 50% of the norovirus strains belonged
      to genotype GII.4, and the predominant strain was GII.4 2006b. Other detected
      genotypes were GII.12, GII.b, GII.3, GII.8, and GII.7. This study highlights the
      importance of screening for norovirus infection in acute gastroenteritis and
      having a reporting system to understand better the epidemiology of norovirus
      infection in Kuwait.

PMID- 23852688
TI  - Human parechovirus and the risk of type 1 diabetes.
AB  - Human parechoviruses (HPeVs) are RNA viruses associated mainly with mild
      gastrointestinal and respiratory infections in children and also cause neonatal
      sepsis and CNS infections. Human enteroviruses, close relatives of HPeVs,
      associate with the development of type 1 diabetes. In this study, the potential
      role of HPeV infections in promoting beta cell autoimmunity was investigated by
      analyzing stool samples of 54 prediabetic case and 134 healthy control children
      for the presence of HPeV RNA and comparing the derived infection frequencies. All
      188 children were participants of the Finnish prospective Diabetes Prediction and
      Prevention study. Viral RNA was screened for using an HPeV-specific RT-PCR method
      coupled to liquid hybridization of the PCR product. The overall HPeV infection
      frequency did not differ between prediabetic case and control children. However,
      case boys had more HPeV positive samples in the 6-month period before becoming
      autoantibody positive, when compared to the matching time-period in controls (P <
      0.01). HPeV infection at a young age does not appear to play a major role in the
      development of beta-cell autoimmunity. In boys, however, HPeVs showed time
      dependent association with the first detection of diabetes-associated
      autoantibodies. Thus, in boys, HPeV infections cannot be excluded as a gender
      specific risk factor which promotes the development of type 1 diabetes.

PMID- 23852689
TI  - Usefulness of ultrasonography in the diagnosis of gout: a meta-analysis.

PMID- 23852690
TI  - Validation of OMERACT preliminary rheumatoid arthritis flare domains in the NOR
      DMARD study.
AB  - OBJECTIVE: Domains identified as a result of qualitative research and Delphi
      exercises to assess rheumatoid arthritis (RA) flare include pain, function,
      swollen and tender joints, patient and physician global, laboratory measures,
      participation, stiffness, self-management and fatigue. Here we examine aspects of
      construct and content validity of these domains in a longitudinal observational
      study. METHODS: A total of 1195 patients with RA treated with non-biological
      disease-modifying antirheumatic drugs (DMARDs) or biologics were eligible for the
      analyses. Working definitions of 'flare' included patient-reported worsening
      between 3 and 6 months (primary) and treatment change at 6 months (DMARDs and/or
      systemic corticosteroids) (secondary). Available outcome measures were mapped to
      the flare domains. Changes between 3 and 6 months were compared between patients
      with and without 'flare'. Convergent and divergent construct validity and content
      validity were assessed by correlation analyses and logistic regression analysis,
      respectively. RESULTS: Applying the flare working definition based on patient
      reported worsening, standardised mean differences (SMDs) were >0.5 for the
      majority of outcomes. The largest SMDs were observed for Pain visual analogue
      scale (1.30), SF-36 Bodily pain (1.24), Patient global (1.20) and morning
      stiffness intensity (1.17). The flare working definition based on treatment
      change yielded lower SMDs (<0.5 for most variables). Consistently stronger
      intradomain than corresponding interdomain correlations supported convergent and
      divergent validity of the domains. CONCLUSIONS: Probing a flare definition via
      outcome measures, the identified flare domains discriminated well between
      patients with and without worsening. Interdomain and intradomain correlation and
      logistic regression analyses provide further support for construct and content
      validity of the identified flare domains.

PMID- 23852691
TI  - Measurement bias in different versions of the Dutch Health Assessment
      Questionnaire Disability Index.

PMID- 23852692
TI  - Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits
      mTORC1 signalling and delays surgically induced osteoarthritis in comparison with
      wild-type mice.
AB  - BACKGROUND: An exogenous supplement of n-3 polyunsaturated fatty acids (PUFAs)
      has been reported to prevent osteoarthritis (OA) through undefined mechanisms.
      OBJECTIVE: This study investigated the effect of alterations in the composition
      of endogenous PUFAs on OA, and associations of PUFAs with mammalian target of
      rapamycin complex 1 (mTORC1) signalling, a critical autophagy pathway in fat-1
      transgenic (TG) mice. METHODS: fat-1 TG and wild-type mice were used to create an
      OA model by resecting the medial meniscus. The composition of the endogenous
      PUFAs in mouse tissues was analysed by gas chromatography, and the incidence of
      OA was evaluated by micro-computed tomography (micro-CT), scanning electron
      microscopy and histological methods. Additionally, primary chondrocytes were
      isolated and cultured. The effect of exogenous and endogenous PUFAs on mTORC1
      activity and autophagy in chondrocytes was assessed. RESULTS: The composition of
      endogenous PUFAs of TG mice was optimised both by increased n-3 PUFAs and
      decreased n-6 PUFAs, which significantly alleviated the articular cartilage
      destruction and osteophytosis in the OA model (p<0.01), decreased protein
      expression of matrix metalloproteinase-13 (MMP-13) and ADAMTS-5 (a disintegrin
      and metalloproteinase with thrombospondin motifs) in the articular cartilage
      (p<0.01) and reduced chondrocyte number and loss of cartilage extracellular
      matrix. Both exogenous and endogenous n-3 PUFAs downregulated mTORC1 activity and
      promoted autophagy in articular chondrocytes. Conversely, mTORC1 pathway
      activation suppressed autophagy in articular chondrocytes. CONCLUSIONS:
      Enhancement of the synthesis of endogenous n-3 PUFAs from n-6 PUFAs can delay the
      incidence of OA, probably through inhibition of mTORC1, promotion of autophagy
      and cell survival in cartilage chondrocytes. Future investigation into the role
      of the endogenous n-6/n-3 PUFAs composition in OA prevention and treatment is
      warranted.

PMID- 23852693
TI  - Inactivation of urokinase-type plasminogen activator receptor (uPAR) gene induces
      dermal and pulmonary fibrosis and peripheral microvasculopathy in mice: a new
      model of experimental scleroderma?
AB  - OBJECTIVE: Urokinase-type plasminogen activator receptor (uPAR) is a key
      component of the fibrinolytic system involved in extracellular matrix remodelling
      and angiogenesis. The cleavage/inactivation of uPAR is a crucial step in
      fibroblast-to-myofibroblast transition and has been implicated in systemic
      sclerosis (SSc) microvasculopathy. In the present study, we investigated whether
      uPAR gene inactivation in mice could result in tissue fibrosis and peripheral
      microvasculopathy resembling human SSc. METHODS: The expression of the native
      full-length form of uPAR in human skin biopsies was determined by
      immunohistochemistry. Skin and lung sections from uPAR-deficient (uPAR(-/-)) and
      wild-type (uPAR(+/+)) mice at 12 and 24 weeks of age were stained with
      haematoxylin-eosin, Masson's trichrome and Picrosirius red. Dermal thickness and
      hydroxyproline content in skin and lungs were quantified. Dermal myofibroblast
      and microvessel counts were determined by immunohistochemistry for alpha-smooth
      muscle actin and CD31, respectively. Endothelial cell apoptosis was assessed by
      TUNEL/CD31 immunofluorescence assay. RESULTS: Full-length uPAR expression was
      significantly downregulated in SSc dermis, especially in fibroblasts and
      endothelial cells. Dermal thickness, collagen content and myofibroblast counts
      were significantly greater in uPAR(-/-) than in uPAR(+/+) mice. In uPAR(-/-)
      mice, dermal fibrosis was paralleled by endothelial cell apoptosis and severe
      loss of microvessels. Lungs from uPAR(-/-) mice displayed non-specific
      interstitial pneumonia-like pathological features, both with inflammation and
      collagen deposition. Pulmonary pathology worsened significantly from 12 to 24
      weeks, as shown by a significant increase in alveolar septal width and collagen
      content. CONCLUSIONS: uPAR(-/-) mice are a new animal model closely mimicking the
      histopathological features of SSc. This model warrants future studies.

PMID- 23852694
TI  - Results from systematic screening for cardiovascular risk in outpatients with
      rheumatoid arthritis in accordance with the EULAR recommendations.
AB  - AIM: To investigate risk factors for the development of cardiovascular disease
      (CVD) and estimate the risk of cardiovascular death in rheumatoid arthritis (RA)
      patients in accordance with EULAR recommendations. MATERIALS AND METHODS:
      Outpatients with RA <=85 years of age from a Danish hospital were invited to
      participate. Patients' risk of cardiovascular death was calculated according to
      the SCORE system, based on total cholesterol/high-density lipoprotein (HDL)
      ratio, smoking habits, blood pressure, age and gender. The SCORE was adjusted
      based on disease duration, IgM-RF/anti-CCP positivity and the presence of extra
      articular manifestations. Factors such as history of CVD, hypertension or
      diabetes mellitus (DM), fasting glucose, exercise habits, body mass index (BMI)
      and waist circumference were explored. RESULTS: 836 patients participated; 71.5%
      women; mean (SD) age 64.3 years (12.0); 152 (19.1%) were already diagnosed with
      CVD and 74 (9.0%) with DM. Among the 644 patients without CVD or DM, 158 (24.5%)
      were smokers, 229 (35.8%) had a systolic blood pressure >=140, 397 (65.6%) total
      cholesterol >=5.0 mM/L, 326 (55.4%) low-density lipoprotein cholesterol >=3.0
      mM/L, 18 (4.0%) women and 19 (12.1%) men had a HDL-cholesterol level below
      1.2/1.0 mM/L. BMI was >25 in 409 (63.8%). Waist circumference was above 80/94 cm
      in 297 (63.3%) of female and 111 (63.8%) of male patients, respectively, and 418
      (64.9%) exercised <=5 times a week. Among patients without DM, 14.3% had a
      fasting glucose >=6.0 mmol/L. The SCORE was >=5 in 122 (20.2%). They were
      referred to follow-up by their GP and community advice services. CONCLUSIONS:
      Systematic screening revealed several risk factors that needed medical follow-up
      or support to initiate lifestyle changes.

PMID- 23852696
TI  - Is early remission associated with improved survival or is arthritis persistency
      associated with increased mortality in early arthritis? Comparisons with the
      general population.

PMID- 23852695
TI  - Efficacy and safety of tanezumab added on to diclofenac sustained release in
      patients with knee or hip osteoarthritis: a double-blind, placebo-controlled,
      parallel-group, multicentre phase III randomised clinical trial.
AB  - OBJECTIVES: Tanezumab, a monoclonal antibody, inhibits nerve growth factor and
      reduces chronic pain. This randomised, double-blind, controlled multicentre study
      was conducted to evaluate the efficacy and safety of tanezumab added to oral
      diclofenac sustained release (DSR) in patients with hip or knee osteoarthritis
      (OA) pain. METHODS: Patients (N=604) with moderate to severe knee or hip OA
      tolerating stable DSR were randomised and treated with DSR 75 mg twice daily
      combined with intravenous tanezumab 10, 5 or 2.5 mg or placebo at weeks 0, 8 and
      16. Co-primary efficacy endpoints (Western Ontario and McMaster Universities OA
      Index (WOMAC) Pain and Physical Function subscales and patient's global
      assessment of OA) were assessed at week 16. RESULTS: All co-primary endpoints
      were significantly improved for all tanezumab+DSR groups versus placebo+DSR
      (p<=0.039). The incidence of adverse events of abnormal peripheral sensation was
      lower than in previous tanezumab trials. No new safety signals emerged. Overall
      incidence of adverse events was higher with tanezumab+DSR (45.2%-49.7%) than with
      placebo+DSR (34.9%); serious adverse event rates were similar across treatments
      (5.3%-7.6%). Osteonecrosis was reported in six of 452 patients with tanezumab+DSR
      (1.3%), but an external adjudication committee did not confirm osteonecrosis in
      any patient. CONCLUSIONS: Addition of tanezumab to DSR resulted in significant
      improvements in pain, function and global assessments in patients with OA.
      Although no new safety signals were observed, the higher incidence of adverse
      events in the tanezumab+diclofenac group suggests that combination therapy is
      unfavourable. Further investigations of tanezumab monotherapy for OA pain
      treatment are required. CLINICAL TRIAL REGISTRATION NUMBER: NCT00864097.

PMID- 23852697
TI  - Population-specific effects of SLC17A1 genotype on serum urate concentrations and
      renal excretion of uric acid during a fructose load.

PMID- 23852698
TI  - High frequency of reactive arthritis in adults after Yersinia pseudotuberculosis
      O:1 outbreak caused by contaminated grated carrots.
AB  - OBJECTIVE: We describe the epidemiological and microbiological process in the
      clearing of a foodborne outbreak of Yersinia pseudotuberculosis O:1 linked to raw
      carrots and frequency of the associated reactive extra-gastrointestinal
      manifestations. METHODS: The patient samples were investigated by routine culture
      or antibody testing methods. The real-time bacterial PCR was used to detect Y
      pseudotuberculosis in samples from the grated carrots and in those taken from the
      carrot storage. Genotype of bacterial isolates was determined by pulsed-field gel
      electrophoresis. For case identification, we retrospectively looked over the
      laboratory files of the central hospital focusing on the time period of the
      outbreak. RESULTS: Altogether 49 case patients were identified. Y
      pseudotuberculosis was detected by real-time PCR analysis in samples taken from
      grated carrots and from the carrot distributor. Bacterial isolates originating
      from the farm environment showed identical serotype (O:1) and genotype (S12) with
      the patients' isolates. Among 37 adults, reactive arthritis (ReA) was found in 8
      (22%) and three adults had probable ReA. Six (67%) out of nine human leucocyte
      antigen (HLA) typed patients with ReA were HLA-B27 positive. Erythema nodosum was
      found in 42% of the 12 children, whereas none of them had definite ReA.
      CONCLUSIONS: In this outbreak, Y pseudotuberculosis was for the first time
      detected in both patient and food samples. ReA was more common than earlier
      reported in the outbreaks associated with this pathogen; the reason may be that
      the previous outbreaks have occurred among children. HLA-B27 frequency was higher
      than usually reported in single-source outbreaks of ReA.

PMID- 23852699
TI  - Transient B-cell depletion combined with apoptotic donor splenocytes induces xeno
      specific T- and B-cell tolerance to islet xenografts.
AB  - Peritransplant infusion of apoptotic donor splenocytes cross-linked with ethylene
      carbodiimide (ECDI-SPs) has been demonstrated to effectively induce allogeneic
      donor-specific tolerance. The objective of the current study is to determine the
      effectiveness and additional requirements for tolerance induction for xenogeneic
      islet transplantation using donor ECDI-SPs. In a rat-to-mouse xenogeneic islet
      transplant model, we show that rat ECDI-SPs alone significantly prolonged islet
      xenograft survival but failed to induce tolerance. In contrast to allogeneic
      donor ECDI-SPs, xenogeneic donor ECDI-SPs induced production of xenodonor
      specific antibodies partially responsible for the eventual islet xenograft
      rejection. Consequently, depletion of B cells prior to infusions of rat ECDI-SPs
      effectively prevented such antibody production and led to the indefinite survival
      of rat islet xenografts. In addition to controlling antibody responses, transient
      B-cell depletion combined with ECDI-SPs synergistically suppressed xenodonor
      specific T-cell priming as well as memory T-cell generation. Reciprocally, after
      initial depletion, the recovered B cells in long-term tolerized mice exhibited
      xenodonor-specific hyporesponsiveness. We conclude that transient B-cell
      depletion combined with donor ECDI-SPs is a robust strategy for induction of
      xenodonor-specific T- and B-cell tolerance. This combinatorial therapy may be a
      promising strategy for tolerance induction for clinical xenogeneic islet
      transplantation. 

PMID- 23852700
TI  - MALDI imaging MS reveals candidate lipid markers of polycystic kidney disease.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is a severe,
      monogenetically inherited kidney and liver disease. PCK rats carrying the
      orthologous mutant gene serve as a model of human disease, and alterations in
      lipid profiles in PCK rats suggest that defined subsets of lipids may be useful
      as molecular disease markers. Whereas MALDI protein imaging mass spectrometry
      (IMS) has become a promising tool for disease classification, widely applicable
      workflows that link MALDI lipid imaging and identification as well as structural
      characterization of candidate disease-classifying marker lipids are lacking.
      Here, we combine selective MALDI imaging of sulfated kidney lipids and Fisher
      discriminant analysis (FDA) of imaging data sets for identification of candidate
      markers of progressive disease in PCK rats. Our study highlights strong increases
      in lower mass lipids as main classifiers of cystic disease. Structure
      determination by high-resolution mass spectrometry identifies these altered
      lipids as taurine-conjugated bile acids. These sulfated lipids are selectively
      elevated in the PCK rat model but not in models of related hepatorenal
      fibrocystic diseases, suggesting that they be molecular markers of the disease
      and that a combination of MALDI imaging with high-resolution MS methods and
      Fisher discriminant data analysis may be applicable for lipid marker discovery. 

PMID- 23852701
TI  - Carbon monoxide decreases endosome-lysosome fusion and inhibits soluble antigen
      presentation by dendritic cells to T cells.
AB  - Heme oxygenase-1 (HO-1) inhibits immune responses and inflammatory reactions via
      the catabolism of heme into carbon monoxide (CO), Fe(2+) , and biliverdin. We
      have previously shown that either induction of HO-1 or treatment with exogenous
      CO inhibits LPS-induced maturation of dendritic cells (DCs) and protects in vivo
      and in vitro antigen-specific inflammation. Here, we evaluated the capacity of HO
      1 and CO to regulate antigen presentation on MHC class I and MHC class II
      molecules by LPS-treated DCs. We observed that HO-1 and CO treatment
      significantly inhibited the capacity of DCs to present soluble antigens to T
      cells. Inhibition was restricted to soluble OVA protein, as no inhibition was
      observed for antigenic OVA-derived peptides, bead-bound OVA protein, or OVA as an
      endogenous antigen. Inhibition of soluble antigen presentation was not due to
      reduced antigen uptake by DCs, as endocytosis remained functional after HO-1
      induction and CO treatment. On the contrary, CO significantly reduced the
      efficiency of fusion between late endosomes and lysosomes and not by phagosomes
      and lysosomes. These data suggest that HO-1 and CO can inhibit the ability of LPS
      treated DCs to present exogenous soluble antigens to naive T cells by blocking
      antigen trafficking at the level of late endosome-lysosome fusion. 

PMID- 23852704
TI  - Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal
      cancers: European group on tumor markers 2014 guidelines update.
AB  - Biomarkers currently play an important role in the detection and management of
      patients with several different types of gastrointestinal cancer, especially
      colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and
      gastrointestinal stromal tumors (GISTs). The aim of this article is to provide
      updated and evidence-based guidelines for the use of biomarkers in the different
      gastrointestinal malignancies. Recommended biomarkers for colorectal cancer
      include an immunochemical-based fecal occult blood test in screening asymptomatic
      subjects >=50 years of age for neoplasia, serial CEA levels in postoperative
      surveillance of stage II and III patients who may be candidates for surgical
      resection or systemic therapy in the event of distant metastasis occurring, K-RAS
      mutation status for identifying patients with advanced disease likely to benefit
      from anti-EGFR therapeutic antibodies and microsatellite instability testing as a
      first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ
      cancers, measurement of HER2 is recommended in selecting patients for treatment
      with trastuzumab. For patients with suspected GIST, determination of KIT protein
      should be used as a diagnostic aid, while KIT mutational analysis may be used for
      treatment planning in patients with diagnosed GISTs.

PMID- 23852706
TI  - Characterization and biocompatibility of glucan: a safe food additive from
      probiotic Lactobacillus plantarum DM5.
AB  - BACKGROUND: Exopolysaccharide produced by lactic acid bacteria are the subject of
      an increasing number of studies for their potential applications in the food
      industry as stabilizing, bio-thickening and immunostimulating agents. In this
      regard, the authors isolated an exopolysaccharide producing probiotic lactic acid
      bacterium from fermented beverage Marcha of north eastern Himalayas. RESULTS: The
      isolate Lactobacillus plantarum DM5 showed extracellular glucansucrase activity
      of 0.48 U mg-1 by synthesizing natural exopolysaccharide glucan (1.87 mg mL-1)
      from sucrose. Zymogram analysis of purified enzyme confirms the presence of
      glucosyltransferase of approximately 148 kDa with optimal activity of 18.7 U mg-1
      at 30  degrees C and pH 5.4. The exopolysaccharide was purified by gel permeation
      chromatography and had an average molecular weight of 1.11 * 106 Da. Acid
      hydrolysis and structural characterization of exopolysaccharide revealed that it
      was composed of d-glucose residues, containing 86.5% of alpha-(1->6) and 13.5% of
      alpha-(1->3) linkages. Rheological study exhibited a shear thinning effect of
      glucan appropriate for food additives. A cytotoxicity test of glucan on human
      embryonic kidney 293 (HEK 293) and human cervical cancer (HeLa) cell lines
      revealed its nontoxic biocompatible nature. CONCLUSION: This is the first report
      on the structure and biocompatibility of homopolysaccharide alpha-D-glucan
      (dextran) from probiotic Lactobacillus plantarum strain and its unique physical
      and rheological properties that facilitate its application in the food industry
      as viscosifying and gelling agent.

PMID- 23852705
TI  - A complete genomic analysis of hepatitis B virus isolated from 516 Chinese
      patients with different clinical manifestations.
AB  - This study investigated features and clinical implications of HBV mutations in
      patients with different clinical manifestations. In total, 516 patients were
      enrolled in this study, including 131 patients with acute hepatitis B, 239
      patients with chronic hepatitis B, and 146 patients with acute-on-chronic liver
      failure. HBV genotypes and mutations were analyzed by direct sequencing of
      complete viral genomes. Genotypes B2, C1, C2, and D1 accounted for 22.2%, 1.6%,
      74.6%, and 1.6%, respectively. Genotype B was more frequently detected in
      patients with acute hepatitis B than those with chronic hepatitis B and acute-on
      chronic liver failure. Deletion mutations were detected mostly in preS1 and preS2
      regions and the detection rates were 3.8%, 19.7%, and 24.7% for acute hepatitis
      B, chronic hepatitis B and acute-on-chronic liver failure patients, respectively.
      Incidences of point mutation T53C (preS1F53L), G1613A (polR841K), G1775A and
      A1762T + G1764A in the basal core promoter region, G1896A and G1899A in precore
      region and A2189C (coreI97L) in core region increased along with acute hepatitis
      B, chronic hepatitis B, and acute-on-chronic liver failure. The mutation G1896A
      was independently associated with poor survival of patients with acute-on-chronic
      liver failure. The gradual increase of viral mutation incidences was also
      observed in three HLA-A2-restricted cytotoxic T lymphocyte epitopes from HLA-A2
      positive patients, that is env188-196 (5.8%, 10.1%, 22.5%), core107-115 (4.3%,
      4.6%, 19.7%), and x92-100 (1.4%, 20.2%, 33.8%). In conclusion, certain viral
      mutations in various regions of HBV genome are associated with disease
      progression of HBV infection.

PMID- 23852707
TI  - Management of CNS-related Disease Manifestations in Patients With Tuberous
      Sclerosis Complex.
AB  - OPINION STATEMENT: Historically, before the advent of modern imaging and genetic
      testing, Tuberous Sclerosis Complex (TSC) was more of a diagnostic challenge and
      less of a treatment challenge. This is because the natural history of TSC was
      poorly understood and TSC-specific treatments were non-existent. In the current
      era, diagnosis is more straightforward but management is much more complex.
      Disease manifestations vary by age, severity, and organ system. Management issues
      in the first few months of life, including neurologic manifestations, are very
      different than late childhood, adolescence, and adulthood. With increasing
      numbers of TSC diagnoses being made prenatally or shortly after birth, the
      opportunity for interventions that may improve long-term developmental and
      epilepsy outcomes now may precede the onset of neurological clinical symptoms.
      Familiarity and anticipation of these neurologic complications and rapid response
      to their emergence is crucial. Periodic imaging surveillance for development of
      subependymal giant cell astrocytoma (SEGA), preferably by magnetic resonance
      imaging (MRI) every 1-3 years, is now standard of care. Early SEGA detection
      provides opportunity to initiate pharmacologic treatment with everolimus if
      appropriate, thereby negating the need for invasive surgery. Routine
      electroencephalography (EEG) in asymptomatic infants for the first year or two of
      life is becoming increasingly accepted, with treatment initiation of vigabatrin
      dependent on concerning EEG findings instead of waiting until onset of clinical
      seizures, the traditional approach. Effective SEGA treatment and optimal seizure
      control remain principal during the first few decades of life for the clinical
      neurologist involved in the management of TSC. However, during the same period
      and extending through adulthood, assessment of TSC-associated neuropsychiatric
      disorder (TAND) is also key to the best clinical outcome and quality of life for
      affected individuals and their surrounding family and caregivers.

PMID- 23852708
TI  - Autoimmune status epilepticus.
AB  - OPINION STATEMENT: Autoimmune status epilepticus is a rare condition but one that
      has been increasingly recognized by neurologists and clinicians in the intensive
      care unit. As more cases are described in the literature and more antibody tests
      become commercially available, diagnosis is now feasible; however, early
      diagnosis remains a challenge. For practical purposes, status epilepticus may be
      considered as possibly autoimmune if it is refractory to anticonvulsant treatment
      and there is no other known cause; this may then lead to empiric immunomodulatory
      therapy. Major factors that raise the index of suspicion are recent cognitive or
      behavioral alterations, a history of malignancy or tumor, or presence of other
      neurological features. There is a lack of high level evidence in the literature
      for treatment of status epilepticus, and almost none for autoimmune encephalitis.
      Patients with autoimmune status epilepticus may be treated with immunomodulatory
      therapy, including steroids, intravenous immunoglobulin (IVIG), plasmapheresis
      (PLEX), and other immunosuppressive agents while maximizing their anticonvulsant
      therapy. For some patients, resective surgery may be necessary, such as
      hemispherectomy for Rasmussen's encephalopathy. In the case of status epilepticus
      due to paraneoplastic autoantibodies, urgent and aggressive testing and treatment
      of a primary malignancy is needed. Importantly, any suspicion of autoimmune
      mediated status epilepticus should prompt the transfer of the patient to a
      specialized center with experience in refractory status epilepticus whenever
      possible.

PMID- 23852709
TI  - Synthesis of some new 3-coumaranone and coumarin derivatives as dual inhibitors
      of acetyl- and butyrylcholinesterase.
AB  - A novel series of coumarin and 3-coumaranone derivatives encompassing the
      phenacyl pyridinium moiety were synthesized and evaluated for their
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity
      using Ellman's method. All compounds presented inhibitory activity against both
      AChE and BuChE in the micromolar range. The molecular docking simulations
      revealed that all compounds were dual binding site inhibitors of AChE. A kinetic
      study was performed and the mechanism of enzyme inhibition was proved to be of
      mixed type. All compounds were tested for their antioxidant activity and no
      significant activity was observed. 

PMID- 23852710
TI  - Crystal structure of conjugated polyketone reductase (CPR-C1) from Candida
      parapsilosis IFO 0708 complexed with NADPH.
AB  - Conjugated polyketone reductase (CPR-C1) from Candida parapsilosis IFO 0708 is a
      member of the aldo-keto reductase (AKR) superfamily and reduces ketopantoyl
      lactone to d-pantoyl lactone in a NADPH-dependent and stereospecific manner. We
      determined the crystal structure of CPR-C1.NADPH complex at 2.20 A resolution.
      CPR-C1 adopted a triose-phosphate isomerase (TIM) barrel fold at the core of the
      structure in which Thr25 and Lys26 of the GXGTX motif bind uniquely to the
      adenosine 2'-phosphate group of NADPH. This finding provides a novel structural
      basis for NADPH binding of the AKR superfamily.

PMID- 23852711
TI  - Fibrolamellar hepatocellular carcinoma with biliary tumor thrombus: an unreported
      association.
AB  - Fibrolamellar hepatocellular carcinoma (FHCC) is a rare malignant tumor of
      hepatocyte origin occurring earlier in life than typical hepatocellular carcinoma
      (HCC). We describe a distinctive case of FHCC with biliary tumor thrombus (BTT)
      in a 25-year-old Caucasian patient, pointing out the imaging features supported
      by histopathology.

PMID- 23852712
TI  - Chloroquine and diazepam for her last sleep.

PMID- 23852713
TI  - Light-induced bistability in the 2 D coordination network
      {[Fe(bbtr)3][BF4]2}infinity : wavelength-selective addressing of molecular spin
      states.
AB  - Whereas the neat polymeric Fe(II) compound {[Fe(bbtr)3 ][ClO4 ]2 }infinity
      (bbtr=1,4-di(1,2,3-triazol-1-yl)butane) shows an abrupt spin transition centered
      at 107 K facilitated by a crystallographic symmetry breaking, in the covalently
      linked 2D coordination network of {[Fe(bbtr)3 ][BF4 ]2 }infinity , Fe(II) stays
      in the high-spin state down to 10 K. However, strong cooperative effects of
      elastic origin result in reversible, persistent, and wavelength-selective
      photoswitching between the low-spin and high-spin manifolds. This compound thus
      shows true light-induced bistability below 100 K. The persistent bidirectional
      optical switching behavior is discussed as a function of temperature, irradiation
      time, and intensity. Crystallographic studies reveal a photoinduced symmetry
      breaking and serve to establish the correlation between structure and cooperative
      effects. The static and kinetic behavior is explicated within the framework of
      the mean-field approximation. 

PMID- 23852714
TI  - Photoinitiated chemical vapor deposition of cytocompatible poly(2-hydroxyethyl
      methacrylate) films.
AB  - Poly(2-hydroxyethyl methacrylate) (pHEMA) is a widely utilized biomaterial due to
      lack of toxicity and suitable mechanical properties; conformal thin pHEMA films
      produced via chemical vapor deposition (CVD) would thus have broad biomedical
      applications. Thin films of pHEMA were deposited using photoinitiated CVD
      (piCVD). Incorporation of ethylene glycol diacrylate (EGDA) into the pHEMA
      polymer film as a crosslinker, confirmed via Fourier transform infrared
      spectroscopy and X-ray photoelectron spectroscopy, resulted in varied swelling
      and degradation behavior. 2-Hydroxyethyl methacrylate-only films showed
      significant thickness loss (up to 40%), possibly due to extraction of low
      molecular-weight species or erosion, after 24 h in aqueous solution, whereas
      films crosslinked with EGDA (9.25-12.4%) were stable for up to 21 days. These
      results differ significantly from those obtained with plasma-polymerized pHEMA,
      which degraded steadily over a 21-day period, even with crosslinking. This
      suggests that the piCVD films differ structurally from those fabricated via
      plasma polymerization (plasma-enhanced CVD). piCVD pHEMA coatings proved to be
      good cell culture materials, with Caco-2 cell attachment and viability comparable
      to results obtained on tissue-culture polystyrene. Thus, thin film CVD pHEMA
      offers the advantage of enabling conformal coating of a cell culture substrate
      with tunable properties depending on method of preparation and incorporation of
      crosslinking agents.

PMID- 23852715
TI  - Unidirectional scaffold-strand arrangement in DNA origami.

PMID- 23852717
TI  - In vitro investigation of amyloid-beta hepatobiliary disposition in sandwich
      cultured primary rat hepatocytes.
AB  - Failure in amyloid-beta (Abeta) systemic clearance across the liver has been
      suggested to play a role in Abeta brain accumulation and thus to contribute
      largely to the pathology of Alzheimer's disease (AD). The purpose of this study
      was to characterize in vitro the transport mechanisms of Abeta40 across the liver
      using sandwich-cultured primary rat hepatocytes (SCHs) and to determine its
      biliary clearance (CL(bile)) and biliary excretion index (BEI%). 125I-Abeta40
      BEI% was time dependent and reached steady state at 30 minutes, with an average
      value of 29.8% and a CL(bile) of 1.47 ml/min per kilogram of body weight. The
      role of low-density lipoprotein receptor-related protein-1 (LRP1) in mediating
      the basolateral uptake of 125I-Abeta40 in SCHs was assessed using receptor
      associated protein (RAP, 2 uM). A significant reduction in 125I-Abeta40 BEI% and
      CL(bile) with RAP was observed, demonstrating a major contribution of LRP1 in
      mediating hepatic uptake of intact 125I-Abeta40 via transcytosis. Furthermore,
      activity studies suggested a lower role of receptor for advanced glycation end
      products (RAGE) in 125I-Abeta40 hepatic uptake. Verapamil (50 uM) and valspodar
      (20 uM) significantly reduced 125I-Abeta40 BEI%, indicating a role for P
      glycoprotein (P-gp) in the biliary excretion of 125I-Abeta40 in SCHs. LRP1- and P
      gp-mediated 125I-Abeta40 biliary excretion was inducible and increased BEI% by
      26% after rifampicin pretreatment. In conclusion, our findings demonstrated that
      besides LRP1, P-gp and, to a lesser extent, RAGE are involved in 125I-Abeta40
      hepatobiliary disposition and support the use of enhancement of Abeta hepatic
      clearance via LRP1 and P-gp induction as a novel therapeutic approach for the
      prevention and treatment of AD.

PMID- 23852718
TI  - Provisional use of myocardial perfusion imaging in patients undergoing exercise
      stress testing: a worthy concept fraught with challenges.

PMID- 23852719
TI  - Comparison of laser-induced damage with forward-firing and diffusing optical
      fiber during laser-assisted lipoplasty.
AB  - BACKGROUND AND OBJECTIVES: Laser-assisted lipoplasty is made possible by using an
      optical fiber that delivers light endoscopically to subcutaneous fat tissue. Most
      optical fibers for laser-assisted lipoplasty are designed to be irradiated in a
      forward direction. In this study, we compared forward-firing fiber and diffusing
      fiber for use in laser-assisted lipoplasty. The effective parameters of the
      ablation pattern which resulted from the laser-induced damage are discussed for
      both systems. In particular, we note the effect resulting from the different beam
      emission patterns and the contours of laser fluence. METHODS: We used two
      different laser delivery systems (a forward-firing fiber and a diffusing fiber)
      to examine how the beam emission pattern affects the laser-assisted coagulation
      and damage pattern of in vitro fat tissues. A porcine liver tissue (water-rich
      tissue) was used as a secondary laser target to investigate how the laser
      assisted coagulation pattern depends on both the type of tissue (water-rich and
      lipid-rich tissue) as well as the delivery system. An evaluation using a digital
      camera and a thermal camera was conducted for the tissue ablation processes in
      order to observe the generated heat transfer in fat and liver. RESULTS: The
      overall shape of the laser-assisted coagulation zone was different from the beam
      emission pattern in the case where a forward-firing fiber was used within fat
      tissue. The center of the laser-affected zone is characterized by the formation
      of a reservoir of melted fat. In the thermal image analysis, there existed a
      discrepancy between the temperature distribution of the fat tissue and the liver
      tissue during the forward-firing fiber irradiation. In the liver tissue ablation
      process, the temperature distribution during the laser ablation also demonstrated
      an elongated ellipse that matches well with the laser-induced damage zone. The
      temperature distribution in fat tissue adhered to a more discoid pattern that
      corresponded to the laser-induced damage zone. CONCLUSIONS: Based on our
      findings, we have proposed mechanisms that can explain the laser-induced damage
      in both tissues when a forward firing fiber is employed as the delivery system.
      In the case of fat tissue, the ablation mechanism can be characterized by the
      reservoir formation of melted lipids while the ablation is characterized as the
      well-known drilling effect for liver tissue.

PMID- 23852720
TI  - Thoracoscopic procedures in pediatric surgery: what is the evidence?
AB  - INTRODUCTION: Video-assisted thoracoscopic surgery (VATS) has gained enormous
      acceptance among pediatric surgeons. However, most studies on advantages of VATS
      do not reach a high level of evidence. According to a recent classification of
      the Oxford Centre for Evidence-Based Medicine (CEBM), studies can be classified
      into Levels 1 to 5 in order of descending quality. We aimed to identify
      comparative studies investigating VATS versus open procedures in pediatric
      surgery and to classify publications according to the CEBM criteria. MATERIALS
      AND METHODS: Systematic review of comparative studies were identified using
      PubMed. Only studies published in English, comparing pediatric VATS with the
      corresponding open operation were included. End points were advantages and
      disadvantages of VATS as compared with the open procedure. Levels of evidence
      were determined using the recent CEBM criteria. RESULTS: A total of 3 meta
      analysis (MA) and 18 retrospective comparative studies (RCS) investigating 5
      different VATS procedures (repair of congenital diaphragmatic hernia [CDH],
      repair of esophageal atresia/tracheoesophageal fistula (EA/TEF), lung resection,
      treatment of pneumothorax, and resection of neuroblastoma) were included in this
      study. No studies of CEBM Level 1 or Level 2 were identified. All studies were
      classified as CEBM Level 3. The advantages of VATS were less postoperative pain
      (CDH repair, EA/TEF repair, and pneumothorax repair), shorter hospital stay (CDH
      repair, EA/TEF repair, lung resection, and pneumothorax), shorter time of
      ventilation and lower Pco 2 (CDH repair), shorter duration of chest drain (lung
      resection), and less blood loss (resection of neuroblastoma). However,
      disadvantages such as higher recurrence rates (CDH repair), higher Pco 2 (EA/TEF
      repair), and longer operative times (CDH and EA/TEF repair) were also identified.
      CONCLUSION: Only RCS on pediatric VATS are available. Therefore, the best
      available evidence is Level 3. Randomized controlled trials comparing VATS and
      the corresponding open procedure are mandatory to obtain the highest possible
      evidence.

PMID- 23852721
TI  - Histologic and immunohistochemical features associated with outcome in neonatal
      necrotizing enterocolitis.
AB  - INTRODUCTION: The aim of the study was to compare histopathologic and
      immunohistochemical markers between survivors and nonsurvivors of surgical
      necrotizing enterocolitis (NEC). METHODS: With appropriate ethical approval,
      archived resection specimens were identified for patients with NEC (Bell Stages
      II and III) for whom outcome data (survival yes/no) were available. For each
      specimen, a severely affected part of the bowel and the least affected area,
      usually the margin, were analyzed. Histologic findings were scored as no
      necrosis/mucosal necrosis/full-thickness necrosis and immunohistochemistry
      staining for inflammatory markers vascular cell adhesion protein (VCAM), CD68,
      CD20, intercellular adhesion molecule (ICAM), human leukocyte antigen (HLA-DR),
      CD3, Cleaved Caspase-3 (CC3), forkhead box P3 (FOXP3), CD62p, and C4d were
      performed and scored on a semiquantitative scale (0; no staining to 10, strong
      extensive staining). All samples were identified by only their study number
      throughout and the samples were analyzed completely blinded to all clinical
      information. Data were compared using chi-square test for trend (histologic data)
      or Mann-Whitney U test. RESULTS: A total of 123 slides from 60 patients (birth
      weight 1.3 +/- 0.1 kg, gestational age at birth 29.3 +/- 0.6 weeks) were
      examined. Seventy-four specimens (60%) were from survivors and 49 specimens (40%)
      were from those who subsequently died. There was no relationship between
      histologic severity of necrosis (none/mucosal/full thickness) and mortality (p =
      0.58). VCAM (adhesion molecule; p = 0.005) and CC3 (a marker of apoptosis,  p =
      0.008) expression was significantly elevated in nonsurvivors, whereas there were
      no differences in CD68, CD20, ICAM, HLA-DR, CD3, FOXP3, CD62p, or C4d expression.
      CONCLUSIONS: There is a poor relationship between histologic severity of bowel
      necrosis and patient survival in infants undergoing bowel resection for NEC.
      There is statistically increased expression of VCAM reflecting severity of
      systemic inflammatory response and evidence of increased apoptosis in the form of
      CC3 expression in those who subsequently die, but no histologic features can
      predict outcome.

PMID- 23852722
TI  - Improved sperm count and motility in young men surgically treated for
      cryptorchidism in the first year of life.
AB  - INTRODUCTION: The timing of surgery in cryptorchidism has been debated for a long
      time. Reports on histology suggest better fertility outcomes with early surgery,
      whereas evidence of long-term improved fertility still lacks sound data. The aim
      of this study is to analyze sperm count and motility in a cohort of young men
      operated on during the first 2 years of life for cryptorchidism. PATIENTS AND
      METHODS: A total of 78 young men (age, 18-26 years) surgically treated for
      cryptorchidism in the second year of life were recalled to evaluate testicular
      volume and sperm count and motility. Of the 78 young men, 51 accepted to
      participate to clinical and sperm evaluation. Relationship between total sperm
      count (TSC), sperm motility (SM), and age at surgery was investigated by Student
      t-test and Fisher test. Patients were divided into two groups: those patients who
      were submitted to surgery in their first year of life (Group A) and those
      patients who were submitted to surgery in their first and the second year of life
      (Group B). We investigated the ratio of those patients with normal sperm count to
      those patients with abnormal sperm count (we defined as normal TSC > 15 million
      and SM > 15%) and compared the mean TSC and SM in the two groups. RESULTS: TSC
      were slightly but not significantly higher in the first group (45.5 +/- 15.5
      million/mL vs. 36.5 +/- 23.6 million/mL, p = 0.107) and SM (30.5% +/- 11.3% vs.
      26.5% +/- 15.4%, p = 0.341). The percentage of patients with normal sperm count
      and motility were significantly higher in the first group: normal TSC was found
      in 26 of 27 patients (96.3%) in Group A versus 18 of 24 patients (75.0%) in Group
      B (p = 0.042), normal SM was found in 26 of 27 patients (96.3%) versus 16 of 24
      patients (66.7%), respectively (p = 0.008). In the two groups, no statistically
      significant difference was found neither in the proportion of patients with
      bilateral cryptorchidism, in the position of the testes, nor in the ratio of
      subjects treated with hormonal therapy before being operated on. CONCLUSIONS: In
      formerly cryptorchid subjects submitted to surgery in the first 2 years of life,
      the percentage of patients with normal sperm count and motility is higher than
      95%, with even better fertility prognosis if orchiopexy is performed in the first
      year of life.

PMID- 23852723
TI  - Pediatric trauma team activation: are we making the right call?
AB  - INTRODUCTION: A regionalized trauma system must be tailored to the trauma
      epidemiology and the trauma care resources of the population it serves. Pediatric
      trauma system in Singapore differs from others because of its geographic
      compactness and relatively low incidence of severe trauma. The scarcity of
      polytrauma highlights the need of a reliable screening system to identify injured
      children who necessitate urgent transport to emergency department (ED) with
      pediatric resuscitation capacity as well as activation of trauma team upon their
      arrival. In this study, the validity of Pediatric Trauma Score (PTS), Glasgow
      Come Scale (GCS), and respiratory rate (RR) in identifying pediatric patients
      with major trauma and receipt of resuscitation is evaluated. PATIENTS AND
      METHODS: After obtaining Institutional Review Board approval, a retrospective
      analysis was performed using data obtained from our trauma registry between
      January 2011 and December 2012. Information pertaining to the demographics,
      causative mechanism, and injury description, resuscitation, admitting
      disciplines, surgical intervention, and outcome were analyzed. The sensitivity
      and specificity of PTS, GCS, and RR to predict outcomes of interest are
      calculated. RESULTS: A total of 92 patients were recruited. From the 92 patients,
      26 sustained major trauma, and 21 patients received ED resuscitation. The mean
      age was 4 years 9 months. Sensitivity and specificity of PTS <= 8, GCS <= 10, and
      abnormal RR for predicting major trauma were 61.5, 77.3; 26.9, 100; and 53.8,
      60.6%; respectively. When the reliability to identify patients received ED
      resuscitation was evaluated the sensitivity and specificity of PTS <= 8, GCS <=
      10, and abnormal RR were 90.5, 83.1; 28.6, 98.6; and 76.2, 66.2%; respectively.
      CONCLUSION: The parameters of PTS need to be further refined to improve its
      accuracy and minimize the undertriage rate. If a combined physiologic and
      anatomic scoring system such as PTS is used, other physiologic parameters such as
      GCS and RR may become redundant. The evaluation of the validity of PTS, GCS, and
      RR in predicting pediatric major trauma indicated poor reliability.

PMID- 23852724
TI  - Amniotic fluid stem cells prevent development of ascites in a neonatal rat model
      of necrotizing enterocolitis.
AB  - AIM: It has been demonstrated that in a neonatal rat model of necrotizing
      enterocolitis (NEC), amniotic fluid stem (AFS) cells decrease intestinal damage
      and improve survival via modulation of stromal cells expressing cyclooxygenase 2
      in the lamina propria. Herein, we aimed to evaluate the effect of AFS cells on
      body weight and fluid retention in this NEC model. Methods AFS cells were
      obtained from green fluorescent protein (GFP) + pregnant rats at E16 and expanded
      in culture. A total of 185 neonatal rats had NEC induced by gavage feeding of
      hypertonic formula + hypoxia + oral lipopolysaccharide (4 mg/kg/d) and were
      randomized to intraperitoneal phosphate buffered saline (PBS, n = 93) or AFS
      cells (n = 92). A total of 36 breastfed (BF) rats were used as controls. All rats
      were being killed at 96 hours of life. Groups were compared for body weight and
      presence of free intraperitoneal fluid using nonparametric and contingency tests.
      Data are expressed as mean +/- standard deviation. RESULTS: There were no
      differences in birth weight among the groups (PBS = 5.6 +/- 0. 3 g; AFS cells =
      5.6 +/- 0. 3 g; BF = 5.6 +/- 0. 3 g; p = 1). The body weight at randomization was
      not different between PBS (5.61 +/- 0. 5 g) and AFS cells (5.60 +/- 0. 5; p = 1)
      rats. After the rats were killed, BF rats were significantly heavier (12.5 +/-
      0.1 g) than PBS (5.12 +/- 0.4 g) and AFS cell rats (4.95 +/- 0.3; p < 0.0001).
      From randomization to being killed, PBS rats had 9% of weight loss in comparison
      with 12% in AFS cell rats (p = 0.08). After the rats were killed, 42 (45%) PBS
      rats developed ascites with evident abdominal distension in comparison with 19
      (21%) AFS cells (p = 0.0005). None of BF animals had ascites. CONCLUSION: Gavage
      feeding and undernutrition severely affect growth in this model of NEC.
      Administration of AFS cells result in lower incidence of ascites than in PBS
      rats. This could explain the differences in body weight between the two groups of
      rats that were killed. Furthermore, studies on liver function and fluid
      composition are needed to investigate our speculation.

PMID- 23852725
TI  - Fast neutron radiotherapy for primary mucosal melanomas of the head and neck.
AB  - BACKGROUND: Primary head and neck mucosal melanomas (HNMMs) are rare tumors
      managed with surgery and/or radiotherapy and associated with poor outcomes. Given
      their radioresistance, high linear energy transfer radiotherapy with neutrons may
      improve local control. METHODS: We conducted a retrospective review of 14
      patients with HNMM treated with neutrons at the University of Washington from
      1990 to 2012. Five patients had T3 disease, 9 had T4 disease, 3 had regional
      nodal disease, and 4 had distant metastases at diagnosis. Primary sites were
      sinonasal (n=10), lip (n=2), and palate (n=2). Ten patients had initial surgical
      resection/debulking. RESULTS: Nine patients had gross residual disease, 6 had
      complete response, and 3 had partial response. Local control was achieved in 79%
      until death or last follow-up, and 50% developed distant metastases. Kaplan-Meier
      5-year local control was 66% and overall survival was 21%. CONCLUSION: High rates
      of locoregional control were achieved with neutrons, despite the presence of
      gross disease. Survival was limited by early distant metastases.

PMID- 23852726
TI  - RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative
      splicing in the honey bee.
AB  - Studies of DNA methylation from fungi, plants, and animals indicate that gene
      body methylation is ancient and highly conserved in eukaryotic genomes, but its
      role has not been clearly defined. It has been postulated that regulation of
      alternative splicing of transcripts was an original function of DNA methylation,
      but a direct experimental test of the effect of methylation on alternative
      slicing at the whole genome level has never been performed. To do this, we
      developed a unique method to administer RNA interference (RNAi) in a high
      throughput and noninvasive manner and then used it to knock down the expression
      of DNA methyl-transferase 3 (dnmt3), which is required for de novo DNA
      methylation. We chose the honey bee (Apis mellifera) for this test because it has
      recently emerged as an important model organism for studying the effects of DNA
      methylation on development and social behavior, and DNA methylation in honey bees
      is predominantly on gene bodies. Here we show that dnmt3 RNAi decreased global
      genomic methylation level as expected and in addition caused widespread and
      diverse changes in alternative splicing in fat tissue. Four different types of
      splicing events were affected by dnmt3 gene knockdown, and change in two types,
      exon skipping and intron retention, was directly related to decreased
      methylation. These results demonstrate that one function of gene body DNA
      methylation is to regulate alternative splicing. 

PMID- 23852727
TI  - Mutation that causes hypertrophic cardiomyopathy increases force production in
      human beta-cardiac myosin.

PMID- 23852728
TI  - Feature Article: mTOR complex 2-Akt signaling at mitochondria-associated
      endoplasmic reticulum membranes (MAM) regulates mitochondrial physiology.
AB  - The target of rapamycin (TOR) is a highly conserved protein kinase and a central
      controller of growth. Mammalian TOR complex 2 (mTORC2) regulates AGC kinase
      family members and is implicated in various disorders, including cancer and
      diabetes. Here we report that mTORC2 is localized to the endoplasmic reticulum
      (ER) subcompartment termed mitochondria-associated ER membrane (MAM). mTORC2
      localization to MAM was growth factor-stimulated, and mTORC2 at MAM interacted
      with the IP3 receptor (IP3R)-Grp75-voltage-dependent anion-selective channel 1 ER
      mitochondrial tethering complex. mTORC2 deficiency disrupted MAM, causing
      mitochondrial defects including increases in mitochondrial membrane potential,
      ATP production, and calcium uptake. mTORC2 controlled MAM integrity and
      mitochondrial function via Akt mediated phosphorylation of the MAM associated
      proteins IP3R, Hexokinase 2, and phosphofurin acidic cluster sorting protein 2.
      Thus, mTORC2 is at the core of a MAM signaling hub that controls growth and
      metabolism. 

PMID- 23852729
TI  - Reconstituting pancreas development from purified progenitor cells reveals genes
      essential for islet differentiation.
AB  - Developmental biology is challenged to reveal the function of numerous candidate
      genes implicated by recent genome-scale studies as regulators of organ
      development and diseases. Recapitulating organogenesis from purified progenitor
      cells that can be genetically manipulated would provide powerful opportunities to
      dissect such gene functions. Here we describe systems for reconstructing pancreas
      development, including islet beta-cell and alpha-cell differentiation, from
      single fetal progenitor cells. A strict requirement for native genetic regulators
      of in vivo pancreas development, such as Ngn3, Arx, and Pax4, revealed the
      authenticity of differentiation programs in vitro. Efficient genetic screens
      permitted by this system revealed that Prdm16 is required for pancreatic islet
      development in vivo. Discovering the function of genes regulating pancreas
      development with our system should enrich strategies for regenerating islets for
      treating diabetes mellitus. 

PMID- 23852730
TI  - CTIP2 is a negative regulator of P-TEFb.
AB  - The positive transcription elongation factor b (P-TEFb) is involved in
      physiological and pathological events including inflammation, cancer, AIDS, and
      cardiac hypertrophy. The balance between its active and inactive form is tightly
      controlled to ensure cellular integrity. We report that the transcriptional
      repressor CTIP2 is a major modulator of P-TEFb activity. CTIP2 copurifies and
      interacts with an inactive P-TEFb complex containing the 7SK snRNA and HEXIM1.
      CTIP2 associates directly with HEXIM1 and, via the loop 2 of the 7SK snRNA, with
      P-TEFb. In this nucleoprotein complex, CTIP2 significantly represses the Cdk9
      kinase activity of P-TEFb. Accordingly, we show that CTIP2 inhibits large sets of
      P-TEFb- and 7SK snRNA-sensitive genes. In hearts of hypertrophic cardiomyopathic
      mice, CTIP2 controls P-TEFb-sensitive pathways involved in the establishment of
      this pathology. Overexpression of the beta-myosin heavy chain protein contributes
      to the pathological cardiac wall thickening. The inactive P-TEFb complex
      associates with CTIP2 at the MYH7 gene promoter to repress its activity. Taken
      together, our results strongly suggest that CTIP2 controls P-TEFb function in
      physiological and pathological conditions. 

PMID- 23852732
TI  - Of mice, men, and inflammation.

PMID- 23852733
TI  - Ric-8 folding of G proteins better explains Ric-8 apparent amplification of G
      protein-coupled receptor signaling.

PMID- 23852731
TI  - A molt timer is involved in the metamorphic molt in Manduca sexta larvae.
AB  - Manduca sexta larvae are a model for growth control in insects, particularly for
      the demonstration of critical weight, a threshold weight that the larva must
      surpass before it can enter metamorphosis on a normal schedule, and the
      inhibitory action of juvenile hormone on this checkpoint. We examined the effects
      of nutrition on allatectomized (CAX) larvae that lack juvenile hormone to impose
      the critical weight checkpoint. Normal larvae respond to prolonged starvation at
      the start of the last larval stage, by extending their subsequent feeding period
      to ensure that they begin metamorphosis above critical weight. CAX larvae, by
      contrast, show no homeostatic adjustment to starvation but start metamorphosis 4
      d after feeding onset, regardless of larval size or the state of development of
      their imaginal discs. By feeding starved CAX larvae for various durations, we
      found that feeding for only 12-24 h was sufficient to result in metamorphosis on
      day 4, regardless of further feeding or body size. Manipulation of diet
      composition showed that protein was the critical macronutrient to initiate this
      timing. This constant period between the start of feeding and the onset of
      metamorphosis suggests that larvae possess a molt timer that establishes a
      minimal time to metamorphosis. Ligation experiments indicate that a portion of
      the timing may occur in the prothoracic glands. This positive system that
      promotes molting and the negative control via the critical weight checkpoint
      provide antagonistic pathways that evolution can modify to adapt growth to the
      ecological needs of different insects. 

PMID- 23852735
TI  - Prevalence of hepatitis C virus infection and genotypes in patient with chronic
      kidney disease undergoing hemodialysis.
AB  - The prevalence of antibodies to HCV varies among Brazilian regions at rates of 8
      16%. Since this virus is transmitted by the parenteral route through blood and
      blood products, patients receiving maintenance hemodialysis therapy are at an
      increased risk of infection. The study was conducted in seven dialysis centers in
      Belem, Para, northern Brazil. Blood samples were collected from 798 patients with
      chronic renal disease treated by hemodialysis. The samples were tested for
      antibodies against HCV and the viral genotype was identified. Sixty-seven (8.4%)
      of the 798 patients studied were anti-HCV positive by ELISA, ranging from 4% to
      14% in different centers. Viral RNA was detected in 5.3% (43/798) of the
      patients; of these, 42 also had anti-HCV antibodies. HCV genotyping revealed
      genotype 1 as the most common, detected in 86.1% (37/43) of the patients,
      followed by genotype 2 in 11.6% (5/43) and genotype 3 in one patient (2.3%). The
      findings of this study highlight the importance of control strategies for
      hepatitis C in hemodialysis patients. Molecular biology methods need to be
      available in these centers to screen for HCV on admission in order to establish
      effective infection control measures.

PMID- 23852734
TI  - FGF15/19 protein levels in the portal blood do not reflect changes in the ileal
      FGF15/19 or hepatic CYP7A1 mRNA levels.
AB  - It has been proposed that bile acid suppression of CYP7A1 gene expression is
      mediated through a gut-liver signaling pathway fibroblast growth factor
      (FGF)15/19-fibroblast growth factor receptor 4 which is initiated by activation
      of farnesoid X receptor in the ileum but not in the liver. This study evaluated
      whether FGF15/19 protein levels in the portal blood reflected changes in FGF15/19
      mRNA in the ileum. Studies were conducted in Sprague Dawley rats and New Zealand
      white rabbits fed regular chow (controls), supplemented with cholesterol (Ch) or
      cholic acid (CA). After feeding CA, ileal FGF15 mRNA increased 8.5-fold in rats
      and FGF19 rose 16-fold in rabbits associated with 62 and 75% reduction of CYP7A1
      mRNA, respectively. Neither FGF15 nor FGF19 protein levels changed in the portal
      blood to correspond with the marked increase of FGF15/19 mRNA levels in the ileum
      or inhibited CYP7A1 expression in the liver. Further, in Ch-fed rats, CYP7A1 mRNA
      increased 1.9-fold (P < 0.001) although FGF15 mRNA levels in the ileum and portal
      blood FGF15 protein levels were not decreased. In Ch-fed rabbits, although FGF19
      mRNA levels in the ileum and liver did not increase significantly, CYP7A1 mRNA
      declined 49% (P < 0.05). We were unable to find corresponding changes of FGF15/19
      protein levels in the portal blood in rats and rabbits where the mRNA levels of
      FGF15/19 in the ileum and CYP7A1 in the liver change significantly. 

PMID- 23852736
TI  - CORR Insights(r): factors associated with survey response in hand surgery
      research.

PMID- 23852737
TI  - Partial two-stage exchange for infected total hip arthroplasty: a preliminary
      report.
AB  - BACKGROUND: One common approach to the infected total hip arthroplasty (THA)
      calls for a staged revision, including removal of all components. However,
      removal of well-fixed femoral components can result in bone loss and compromised
      fixation; it is not known whether it is effective to leave a well-fixed femoral
      component in situ, remove only the acetabular component, debride thoroughly,
      place a spacer, and delay reimplantation. QUESTIONS/PURPOSES: The purposes of
      this study were to determine (1) the frequency of infection recurrence; (2) the
      frequency of death; and (3) the Harris hip scores of patients treated with a "two
      stage partial exchange" approach. METHODS: A retrospective analysis from 2000
      through January 2011 revealed 19 patients with infected THA treated with partial
      two-stage exchange including complete acetabular component removal, aggressive
      soft tissue debridement, retention of the well-fixed femoral stem, placement of
      an antibiotic-laden cement femoral head on the trunnion of the retained stem,
      postoperative course of antibiotics, and delayed reimplantation. Indications for
      this treatment included those patients whose femoral component was determined to
      be well fixed and its removal would result in significant femoral bone loss and
      compromise of future fixation. During the study period, this represented 7% (19
      of 262) of the patients whom we treated for a chronically infected THA. Minimum
      followup was 2 years (mean, 4 years; range, 2-11 years). None of the 19 patients
      in this series were lost to followup. We defined failure as recurrence of
      infection in the same hip or the use of long-term suppressive antibiotics.
      RESULTS: Two patients (11%), both with prior failure of two-staged treatment of
      infection, failed secondary to recurrence of infection at an average of 3.3
      years. There were no patient deaths within 90 days. The mean Harris hip score was
      68 (range, 31-100; best score is 100). CONCLUSIONS: Insofar as 89% of patients in
      this series were clinically free of infection at a minimum of 2 years, we believe
      partial two-stage exchange may represent an acceptable option for patients with
      infected THA when femoral component removal would result in significant bone loss
      and compromise of reconstruction. Further study is required on this approach.

PMID- 23852739
TI  - The myosin start-of-power stroke state and how actin binding drives the power
      stroke.
AB  - We propose that on binding to actin at the start of the power stroke the myosin
      cross-bridge takes on the rigor configuration at the actin interface. Starting
      from the prepower stroke state, this can be achieved by a small movement (16
      degrees  rotation) of the lower 50K domain without twisting the central beta
      sheet or opening switch-1 or switch-2. The movement of the lower 50K domain puts
      a strain on the W-helix. This strain tries to twist the beta-sheet, which could
      drive the power stroke. This would provide a coupling between actin binding and
      the execution of the power stroke. During the power stroke the beta-sheet twists,
      moving the P-loop away from switch-2, which opens the nucleotide binding pocket
      and separates ADP from Pi . The power stroke is different from the recovery
      stroke because the upper and lower 50K domains are tethered in the rigor
      configuration.

PMID- 23852738
TI  - Optimized E. coli expression strain LOBSTR eliminates common contaminants from
      His-tag purification.
AB  - His-tag affinity purification is one of the most commonly used methods to purify
      recombinant proteins expressed in E. coli. One drawback of using the His-tag is
      the co-purification of contaminating histidine-rich E. coli proteins. We
      engineered a new E. coli expression strain, LOBSTR (low background strain), which
      eliminates the most abundant contaminants. LOBSTR is derived from the E. coli
      BL21(DE3) strain and carries genomically modified copies of arnA and slyD, whose
      protein products exhibit reduced affinities to Ni and Co resins, resulting in a
      much higher purity of the target protein. The use of LOBSTR enables the pursuit
      of challenging low-expressing protein targets by reducing background
      contamination with no additional purification steps, materials, or costs, and
      thus pushes the limits of standard His-tag purifications.

PMID- 23852740
TI  - An energy-efficient, adiabatic electrode stimulator with inductive energy
      recycling and feedback current regulation.
AB  - In this paper, we present a novel energy-efficient electrode stimulator. Our
      stimulator uses inductive storage and recycling of energy in a dynamic power
      supply. This supply drives an electrode in an adiabatic fashion such that energy
      consumption is minimized. It also utilizes a shunt current-sensor to monitor and
      regulate the current through the electrode via feedback, thus enabling flexible
      and safe stimulation. Since there are no explicit current sources or current
      limiters, wasteful energy dissipation across such elements is naturally avoided.
      The dynamic power supply allows efficient transfer of energy both to and from the
      electrode and is based on a DC-DC converter topology that we use in a
      bidirectional fashion in forward-buck or reverse-boost modes. In an exemplary
      electrode implementation intended for neural stimulation, we show how the
      stimulator combines the efficiency of voltage control and the safety and accuracy
      of current control in a single low-power integrated-circuit built in a standard
      .35 MUm CMOS process. This stimulator achieves a 2x-3x reduction in energy
      consumption as compared to a conventional current-source-based stimulator
      operating from a fixed power supply. We perform a theoretical analysis of the
      energy efficiency that is in accord with experimental measurements. This
      theoretical analysis reveals that further improvements in energy efficiency may
      be achievable with better implementations in the future. Our electrode stimulator
      could be widely useful for neural, cardiac, retinal, cochlear, muscular and other
      biomedical implants where low power operation is important. 

PMID- 23852741
TI  - High-level energy estimation in the sub-VT domain: simulation and measurement of
      a cardiac event detector.
AB  - This paper presents a flow that is suitable to estimate energy dissipation of
      digital standard-cell based designs which are determined to operate in the
      subthreshold regime. The flow is applicable on gate-level netlists, where back
      annotated toggle information is used to find the minimum energy operation point,
      corresponding maximum clock frequency, as well as the dissipated energy per clock
      cycle. The application of the model is demonstrated by exploring the energy
      efficiency of pipelining, retiming, and register balancing. Simulation results,
      which are obtained during a fraction of SPICE simulation time, are validated by
      measurements on a wavelet-based cardiac event detector that was fabricated in 65
      nm low-leakage high-threshold technology. The mean of the absolute modeling error
      is calculated as 5.2%, with a standard deviation of 6.6% over the measurement
      points. The cardiac event detector dissipates 0.88 pJ/sample at a supply voltage
      of 320 mV. 

PMID- 23852742
TI  - Wireless front-end with power management for an implantable cardiac
      microstimulator.
AB  - Inductive coupling is presented with the help of a high-efficiency Class-E power
      amplifier for an implantable cardiac microstimulator. The external coil
      inductively transmits power and data with a carrier frequency of 256 kHz into the
      internal coil of electronic devices inside the body. The detected cardiac signal
      is fed back to the external device with the same pair of coils to save on space
      in the telemetry device. To maintain the power reliability of the microstimulator
      for long-term use, two small rechargeable batteries are employed to supply
      voltage to the internal circuits. The power management unit, which includes radio
      frequency front-end circuits with battery charging and detection functions, is
      used for the supply control. For cardiac stimulation, a high-efficiency charge
      pump is also proposed in the present paper to generate a stimulated voltage of
      3.2 V under a 1 V supply voltage. A phase-locked-loop (PLL)-based phase shift
      keying demodulator is implemented to efficiently extract the data and clock from
      an inductive AC signal. The circuits, with an area of 0.45 mm2, are implemented
      in a TSMC 0.35 MUm 2P4M standard CMOS process. Measurement results reveal that
      power can be extracted from the inductive coupling and stored in rechargeable
      batteries, which are controlled by the power management unit, when one of the
      batteries is drained. Moreover, the data and clock can be precisely recovered
      from the coil coupling, and a stimulated voltage of 3.2 V can be readily
      generated by the proposed charge-pump circuits to stimulate cardiac tissues.

PMID- 23852743
TI  - A new dual current-mode controller improves power regulation in electrosurgical
      generators.
AB  - A new dual current-mode controller produces a fast, accurate constant-power high
      frequency ac output, with maximum current and voltage limits for an
      electrosurgical generator. The regulation of ac output power is achieved with
      near-deadbeat control, without measurement or feedback of the output voltage or
      current. Compared to existing technology, the prototype generator reduces
      unintended tissue damage by significantly improving regulation of output power,
      while reducing complexity and parts count. 

PMID- 23852744
TI  - An Electronic Patch for wearable health monitoring by reflectance pulse oximetry.
AB  - We report the development of an Electronic Patch for wearable health monitoring.
      The Electronic Patch is a new health monitoring system incorporating biomedical
      sensors, microelectronics, radio frequency (RF) communication, and a battery
      embedded in a 3-dimensional hydrocolloid polymer. In this paper the Electronic
      Patch is demonstrated with a new optical biomedical sensor for reflectance pulse
      oximetry so that the Electronic Patch in this case can measure the pulse and the
      oxygen saturation. The reflectance pulse oximetry solution is based on a recently
      developed annular backside silicon photodiode to enable low power consumption by
      the light emitting components. The Electronic Patch has a disposable part of soft
      adhesive hydrocolloid polymer and a reusable part of hard polylaurinlactam. The
      disposable part contains the battery. The reusable part contains the reflectance
      pulse oximetry sensor and microelectronics. The reusable part is 'clicked' into
      the disposable part when the patch is prepared for use. The patch has a size of
      88 mm by 60 mm and a thickness of 5 mm. 

PMID- 23852745
TI  - Onboard tagging for real-time quality assessment of photoplethysmograms acquired
      by a wireless reflectance pulse oximeter.
AB  - Onboard assessment of photoplethysmogram (PPG) quality could reduce unnecessary
      data transmission on battery-powered wireless pulse oximeters and improve the
      viability of the electronic patient records to which these data are stored. These
      algorithms show promise to increase the intelligence level of former "dumb"
      medical devices: devices that acquire and forward data but leave data
      interpretation to the clinician or host system. To this end, the authors have
      developed a unique onboard feature detection algorithm to assess the quality of
      PPGs acquired with a custom reflectance mode, wireless pulse oximeter. The
      algorithm uses a Bayesian hypothesis testing method to analyze four features
      extracted from raw and decimated PPG data in order to determine whether the
      original data comprise valid PPG waveforms or whether they are corrupted by
      motion or other environmental influences. Based on these results, the algorithm
      further calculates heart rate and blood oxygen saturation from a "compact
      representation" structure. PPG data were collected from 47 subjects to train the
      feature detection algorithm and to gauge their performance. A MATLAB interface
      was also developed to visualize the features extracted, the algorithm flow, and
      the decision results, where all algorithm-related parameters and decisions were
      ascertained on the wireless unit prior to transmission. For the data sets
      acquired here, the algorithm was 99% effective in identifying clean, usable PPGs
      versus nonsaturated data that did not demonstrate meaningful pulsatile
      waveshapes, PPGs corrupted by motion artifact, and data affected by signal
      saturation. 

PMID- 23852746
TI  - Small-signal neural models and their applications.
AB  - This paper introduces the use of the concept of small-signal analysis, commonly
      used in circuit design, for understanding neural models. We show that neural
      models, varying in complexity from Hodgkin-Huxley to integrate and fire have
      similar small-signal models when their corresponding differential equations are
      close to the same bifurcation with respect to input current. Three applications
      of small-signal neural models are shown. First, some of the properties of
      cortical neurons described by Izhikevich are explained intuitively through small
      signal analysis. Second, we use small-signal models for deriving parameters for a
      simple neural model (such as resonate and fire) from a more complicated but
      biophysically relevant one like Morris-Lecar. We show similarity in the
      subthreshold behavior of the simple and complicated model when they are close to
      a Hopf bifurcation and a saddle-node bifurcation. Hence, this is useful to
      correctly tune simple neural models for large-scale cortical simulations. Finaly,
      the biasing regime of a silicon ion channel is derived by comparing its small
      signal model with a Hodgkin-Huxley-type model. 

PMID- 23852747
TI  - Modeling and implementation of voltage-mode CMOS dendrites on a reconfigurable
      analog platform.
AB  - Many decades ago, Wilfrid Rall and others laid the foundations for mathematical
      modeling of dendrites using cable theory. With reconfigurable analog
      architectures, we are now able to accurately program different circuit
      architectures to emulate dendrites. Our work has shown that these circuits
      accurately reproduce results predicted from cable theory when inputs to the
      system are small. For large inputs, interesting nonlinear effects begin to take
      hold. 

PMID- 23852748
TI  - The human eye proteome project.
AB  - The human eye proteome is the latest addition to the HUPO Human Proteome Project
      (HPP). Semba et al. (The Human Eye Proteome Project: Perspectives on an emerging
      proteome. Proteomics 2013, 13, 2500-2511) establish a provisional baseline for
      the proteomes of the many anatomical compartments of the eye, based on literature
      review. As part of the Biology and Disease-driven HPP, they and their colleagues
      will generate fresh data and meet the stringent guidelines for protein
      identification and characterization as established by the HPP. 

PMID- 23852749
TI  - Graphene oxide nanoparticles for enhanced photothermal cancer cell therapy under
      the irradiation of a femtosecond laser beam.
AB  - Nano-sized graphene and graphene oxide (GO) are promising for biomedical
      applications, such as drug delivery and photothermal therapy of cancer. It is
      observed in this work that the ultrafast reduction of GO nanoparticles (GONs)
      with a femtosecond laser beam creates extensive microbubbling. To understand the
      surface chemistry of GONs on the microbubble formation, the GONs were reduced to
      remove most of the oxygen-containing groups to get reduced GONs (rGONs).
      Microbubbling was not observed when the rGONs were irradiated by the laser. The
      instant collapse of the microbubbles may produce microcavitation effect that
      brings about localized mechanical damage. To understand the potential
      applications of this phenomenon, cancer cells labeled with GONs or rGONs were
      irradiated with the laser. Interestingly, the microbubbling effect greatly
      facilitated the destruction of cancer cells. When microbubbles were produced, the
      effective laser power was reduced to less than half of what is needed when
      microbubbling is absent. This finding will contribute to the safe application of
      femtosecond laser in the medical area by taking advantage of the ultrafast
      reduction of GONs. It may also find other important applications that need highly
      localized microcavitation effects.

PMID- 23852750
TI  - Recurrent syncope: a slow heart rate?

PMID- 23852751
TI  - Cardiovascular morbidity in long-term survivors of early-onset cancer: a
      population-based study.
AB  - Improvements in cancer therapy have resulted in an expanding population of early
      onset cancer survivors. In contrast to childhood and adolescent cancer survivors,
      there is still a lack of data concerning late morbidities among young adult (YA)
      cancer survivors. Thus, our aim was to investigate cardiac and vascular morbidity
      among early-onset cancer survivors with a special interest in YA cancer
      survivors. In a population-based setting, we explored the risk of cardiovascular
      disease in early-onset cancer survivors compared to healthy siblings. Patients
      diagnosed with cancer below 35 years of age since 1975 were identified from the
      Finnish Cancer Registry, and 5-year survivors were included in our study (N =
      13,860). Information on cardiovascular morbidity was collected from the national
      hospital discharge registry. Compared to siblings, cancer survivors aged 0-19 and
      20-34 at diagnosis had significantly elevated hazard ratios (HRs) for the studied
      outcomes: HR 13.5 (95% CI 8.9-20.4) and 3.6 (95% CI 2.8-4.6) for
      cardiomyopathy/cardiac insufficiency; HR 3.4 (95% CI 2.3-5.1) and 1.7 (95% CI 1.4
      2.0) for atherosclerosis/brain vascular thrombosis; HR 3.3 (95% CI 1.7-6.5) and
      1.8 (95% CI 1.5-2.1) for myocardial infarction/cardiac ischemia and HR 1.7 (95%
      CI 1.2-2.6) and 1.4 (95% CI 1.2-1.7) for cardiac arrhythmia. In both groups,
      depending on the outcome, the HR for adverse events was highest among lymphoma,
      brain tumor, leukemia and testicular malignancy survivors. Our results regarding
      late effects of childhood cancer survivors confirmed previous findings.
      Additionally, our study provides novel information concerning the YA cancer
      survivor population. Hence, our data may help in planning the risk-based long
      term follow-up of early-onset cancer survivors. 

PMID- 23852752
TI  - Modular columnar supramolecular polymers as scaffolds for biomedical
      applications.
AB  - Self-assembly of discotic molecules into supramolecular polymers offers a
      flexible approach for the generation of multicomponent one-dimensional columnar
      architectures with tuneable biomedical properties. Decoration with ligands
      induces specific binding of the self-assembled scaffold to biological targets.
      The modular design allows the easy co-assembly of different discotics for the
      generation of probes for targeted imaging and cellular targeting with adjustable
      ligand density and composition. 

PMID- 23852753
TI  - A real-time multi-channel monitoring system for stem cell culture process.
AB  - A novel, up to 128 channels, multi-parametric physiological measurement system
      suitable for monitoring hematopoietic stem cell culture processes and cell
      cultures in general is presented in this paper. The system aims to measure in
      real-time the most important physical and chemical culture parameters of
      hematopoietic stem cells, including physicochemical parameters, nutrients, and
      metabolites, in a long-term culture process. The overarching scope of this
      research effort is to control and optimize the whole bioprocess by means of the
      acquisition of real-time quantitative physiological information from the culture.
      The system is designed in a modular manner. Each hardware module can operate as
      an independent gain programmable, level shift adjustable, 16 channel data
      acquisition system specific to a sensor type. Up to eight such data acquisition
      modules can be combined and connected to the host PC to realize the whole system
      hardware. The control of data acquisition and the subsequent management of data
      is performed by the system's software which is coded in LabVIEW. Preliminary
      experimental results presented here show that the system not only has the ability
      to interface to various types of sensors allowing the monitoring of different
      types of culture parameters. Moreover, it can capture dynamic variations of
      culture parameters by means of real-time multi-channel measurements thus
      providing additional information on both temporal and spatial profiles of these
      parameters within a bioreactor. The system is by no means constrained in the
      hematopoietic stem cell culture field only. It is suitable for cell growth
      monitoring applications in general. 

PMID- 23852754
TI  - Bio-Microfluidics Real-Time Monitoring Using CNN Technology.
AB  - A new non-invasive real-time system for the monitoring and control of
      microfluidodynamic phenomena involving transport of particles and two phase
      fluids is proposed. The general purpose design of such system is suitable for in
      vitro and in vivo experimental setup and, therefore, for microfluidic
      applications in the biomedical field, such as lab-on-chip and for research
      studies in the field of microcirculation. The system consists of an ad hoc
      optical setup for image magnification providing images suitable for acquisition
      and processing. The main feature of the optical system is the accessibility of
      the information at any point of the optical path. It was designed and developed
      using discrete opto-mechanic components mounted on a breadboard. The optical
      sensing, acquisition, and processing were all performed using an integrated
      vision system based on cellular nonlinear networks (CNNs) analogic (analog plus
      logic) technology called focal plane processor (FPP, Eye-RIS, Anafocus) that was
      inserted in the optical path. Ad hoc algorithms were implemented for the real
      time analysis and extraction of fluidodynamic parameters in micro-channels. They
      were firstly tested on sequences of images recorded during in vivo
      microcirculation experiments on hamsters and then applied on images acquired and
      processed in real-time during in vitro experiments on two-phase fluid flow in a
      continuous microfluidic device (serpentine mixer, ThinXXS). 

PMID- 23852755
TI  - An address-event fall detector for assisted living applications.
AB  - In this paper, we describe an address-event vision system designed to detect
      accidental falls in elderly home care applications. The system raises an alarm
      when a fall hazard is detected. We use an asynchronous temporal contrast vision
      sensor which features sub-millisecond temporal resolution. The sensor reports a
      fall at ten times higher temporal resolution than a frame-based camera and shows
      84% higher bandwidth efficiency as it transmits fall events. A lightweight
      algorithm computes an instantaneous motion vector and reports fall events. We are
      able to distinguish fall events from normal human behavior, such as walking,
      crouching down, and sitting down. Our system is robust to the monitored person's
      spatial position in a room and presence of pets. 

PMID- 23852756
TI  - Wearable monitoring of seated spinal posture.
AB  - This work describes the evaluation of a wearable plastic optical fiber (POF)
      sensor for monitoring seated spinal posture, as compared to a conventional expert
      visual analysis, and the development of a field-deployable posture monitoring
      system. A garment-integrated POF sensor was developed and tested on nine healthy
      subjects. Data from the wearable sensor were compared to data taken
      simultaneously from a marker-based motion capture system, for accuracy and
      reliability. Peak analysis of the resulting data showed a mean time error of 0.53
      plusmn 0.8 s, and a mean value error of 0.64 plusmn 3.1 deg, which represents
      14.5% of the average range of motion. Expert determination of transitional (good
      to bad) posture showed a variation of 20.9% of range of motion. These results
      indicate that the wearable sensor approximates the accuracy of expert visual
      analysis, and provides sufficient accuracy of measurement to reliably monitor
      seated spinal posture. 

PMID- 23852757
TI  - A partial-current-steering biphasic stimulation driver for vestibular prostheses.
AB  - This paper describes a novel partial-current-steering stimulation circuit for
      implantable vestibular prostheses. The drive hardware momentarily delivers a
      charge-balanced asymmetric stimulus to a dummy load before steering towards the
      stimulation electrodes. In this fashion, power is conserved while still gaining
      from the benefits of current steering. The circuit has been designed to be
      digitally programmable as part of an implantable vestibular prosthesis. The
      hardware has been implemented in AMS 0.35 mum 2P4M CMOS technology. 

PMID- 23852758
TI  - Robust engineered circuit design principles for stochastic biochemical networks
      with parameter uncertainties and disturbances.
AB  - Biochemical regulatory networks including genes, proteins and other regulatory
      molecules suffer from internal parametrical fluctuations (thermal,
      transcriptional, and splicing) as well as external noises (environmental and
      intercellular). Robustness is an essential property of intracellular biochemical
      regulatory networks to attenuate the effects of internal fluctuation and external
      noise. In this study, several system control schemes are proposed for the robust
      circuit control design of stochastic linear and nonlinear biochemical regulatory
      networks. First, the robust stability of genetic and proteomic regulatory
      networks is discussed under internal fluctuations. Then, the filtering ability of
      external noises is analyzed for stochastic biochemical regulatory networks. For
      the case where a biochemical regulatory network is not sufficiently robust to
      tolerate internal fluctuation and does not have enough filtering ability to
      filter the external noise, how to improve the robustness and noise filtering
      ability of stochastic biochemical regulatory networks by engineered control
      mechanisms is also proposed via biochemical circuit design. The proposed robust
      gene circuit design principles have potential applications for robust
      biosynthetic network design. Finally, two design examples are given in-silico to
      illustrate the design procedure and to confirm the performance of the proposed
      robust circuit design method. 

PMID- 23852759
TI  - Effects of cigarette smoking on HDL quantity and function: implications for
      atherosclerosis.
AB  - Cigarette smoking has been identified as an independent and preventable risk
      factor for atherosclerosis and cardiovascular disease. Population studies have
      shown that plasma high density lipoprotein (HDL) cholesterol levels are inversely
      related to the risk of developing cardiovascular disease. Cigarette smoking is
      associated with reduced HDL cholesterol levels. Cigarette smoking can alter the
      critical enzymes of lipid transport, lowering lecithin: cholesterol
      acyltransferase (LCAT) activity and altering cholesterol ester transfer protein
      (CETP) and hepatic lipase activity, which attributes to its impact on HDL
      metabolism and HDL subfractions distribution. In addition, HDL is susceptible to
      oxidative modifications by cigarette smoking, which makes HDL become
      dysfunctional and lose its atheroprotective properties in smokers. Therefore,
      cigarette smoking has a negative impact on both HDL quantity and function, which
      can explain, in part, the increased risk of cardiovascular disease in smokers.

PMID- 23852760
TI  - Treatment of a patient with small fiber pathology using nerve biopsy and
      grafting: a case report.
AB  - Small fiber pathology is a common clinical entity with a variable clinical
      presentation and etiology. Unfortunately, little has been described regarding its
      treatment because a majority of cases are idiopathic. Hence, treatment often
      consists of symptomatic management of pain and autonomic dysfunction. This report
      describes a patient who was presented with an undiagnosed pain syndrome thought
      to be affecting nerves within both lower extremities and causing significant
      pain. A sural nerve biopsy was performed for diagnostic purposes and nerve repair
      was performed using Avance nerve allograft (AxoGen Inc., Alachua, FL). Light
      microscopic evaluation was unremarkable, but electron microscopy revealed small
      fiber pathology. Postoperatively, the patient experienced a complete resolution
      of her pain on the involved extremity. These results suggest a potential, novel
      approach for treatment of such cases and possible mechanisms for the patient's
      clinical improvement are explored.

PMID- 23852761
TI  - Fate of a second perforator free flap used to salvage failure of the first
      perforator free flap.
AB  - Perforator flaps should no longer be considered an exotic or complicated option
      for microsurgical tissue transfer. However, despite a proper design and attention
      to detail, as with any free flap, failure can be anticipated sometimes to occur.
      If a free flap is then still indicated, the big question is what to do next? In
      our series of 314 perforator free flaps over the past decade, 21 (7%) total
      failures occurred. A second free flap was attempted for 17 (81%) of these cases.
      Overall these were successful for 16 (94%) patients, including 11 perforator free
      flaps that were 100% successful. The anterolateral thigh (ALT) free flap proved
      to be the "workhorse" alternative. It can be concluded that if failure of a free
      flap can best be rectified by a second free flap, failure of a perforator free
      flap can also be reliably salvaged by a second perforator free flap. 

PMID- 23852762
TI  - Cardiovascular risk stratification in rheumatic diseases: carotid ultrasound is
      more sensitive than Coronary Artery Calcification Score to detect subclinical
      atherosclerosis in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the ability of Coronary Artery Calcification Score (CACS)
      and carotid ultrasonography in detecting subclinical atherosclerosis in
      rheumatoid arthritis (RA). METHODS: A set of 104 consecutive RA patients without
      history of cardiovascular (CV) events were studied to determine CACS, carotid
      intima-media thickness (cIMT) and plaques. Systematic Coronary Risk Evaluation
      (SCORE) modified according to the EULAR recommendations (mSCORE) was also
      assessed. RESULTS: The mean disease duration was 10.8 years, 72.1% had rheumatoid
      factor and/or anti-CCP positivity and 16.4% extra-articular manifestations. Nine
      were excluded because they had type 2 diabetes mellitus or chronic kidney
      disease. CV risk was categorised in the remaining 95 RA patients according to the
      mSCORE as follows: low (n=21), moderate (n=60) and high/very high risk (n=14).
      Most patients with low mSCORE (16/21; 76.2%) had normal CACS (zero), and none of
      them CACS>100. However, a high number of patients with carotid plaques was
      disclosed in the groups with CACS 0 (23/40; 57.5%) or CACS 1-100 (29/38; 76.3%).
      72 (75.8%) of the 95 patients fulfilled definitions for high/very high CV as they
      had an mSCORE >=5% or mSCORE <5% plus one of the following findings: severe
      carotid ultrasonography findings (cIMT>0.9 mm and/or plaques) or CACS>100. A
      CACS>100 showed sensitivity similar to mSCORE (23.6% vs 19.4%). In contrast, the
      presence of severe carotid ultrasonography findings allowed identifying most
      patients who met definitions for high/very high CV risk (70/72; sensitivity 97.2%
      (95% CI 90.3 to 99.7)). CONCLUSIONS: Carotid ultrasonography is more sensitive
      than CACS for the detection of subclinical atherosclerosis in RA.

PMID- 23852763
TI  - Non-viral opportunistic infections in new users of tumour necrosis factor
      inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER)
      study.
AB  - OBJECTIVES: To determine among patients with autoimmune diseases in the USA
      whether the risk of non-viral opportunistic infections (OI) was increased among
      new users of tumour necrosis factor alpha inhibitors (TNFI), when compared to
      users of non-biological agents used for active disease. METHODS: We identified
      new users of TNFI among cohorts of rheumatoid arthritis (RA), inflammatory bowel
      disease and psoriasis-psoriatic arthritis-ankylosing spondylitis patients during
      1998-2007 using combined data from Kaiser Permanente Northern California, two
      pharmaceutical assistance programmes for the elderly, Tennessee Medicaid and US
      Medicaid/Medicare programmes. We compared incidence of non-viral OI among new
      TNFI users and patients initiating non-biological disease-modifying antirheumatic
      drugs (DMARD) overall and within each disease cohort. Cox regression models were
      used to compare propensity-score and steroid- adjusted OI incidence between new
      TNFI and non-biological DMARD users. RESULTS: Within a cohort of 33 324 new TNFI
      users we identified 80 non-viral OI, the most common of which was pneumocystosis
      (n=16). In the combined cohort, crude rates of non-viral OI among new users of
      TNFI compared to those initiating non-biological DMARD was 2.7 versus 1.7 per
      1000-person-years (aHR 1.6, 95% CI 1.0 to 2.6). Baseline corticosteroid use was
      associated with non-viral OI (aHR 2.5, 95% CI 1.5 to 4.0). In the RA cohort,
      rates of non-viral OI among new users of infliximab were higher when compared to
      patients newly starting non-biological DMARD (aHR 2.6, 95% CI 1.2 to 5.6) or new
      etanercept users (aHR 2.9, 95% CI 1.5 to 5.4). CONCLUSIONS: In the USA, the rate
      of non-viral OI was higher among new users of TNFI with autoimmune diseases
      compared to non-biological DMARD users.

PMID- 23852764
TI  - Augmented pain behavioural responses to intra-articular injection of nerve growth
      factor in two animal models of osteoarthritis.
AB  - OBJECTIVES: Nerve growth factor (NGF) is a promising analgesic target,
      particularly in osteoarthritis (OA) where existing therapies are inadequate. We
      hypothesised that pain responses to NGF are increased in OA joints. Here, NGF
      evoked pain behaviour was compared in two rodent models of OA, and possible
      mechanisms underlying altered pain responses were examined. METHODS: OA was
      induced in rat knees by meniscal transection (MNX) or intra-articular monosodium
      iodoacetate injection (MIA). Once OA pathology was fully established (day 20), we
      assessed pain behaviour (hindlimb weight-bearing asymmetry and hindpaw mechanical
      withdrawal thresholds) evoked by intra-articular injection of NGF (10 ug).
      Possible mechanisms underlying alterations in NGF-induced pain behaviour were
      explored using indomethacin pretreatment, histopathological evaluation of
      synovitis, and rtPCR for NGF receptor (tropomyosin receptor kinase (Trk)-A)
      expression in dorsal root ganglia (DRG). RESULTS: Both the MIA and MNX models of
      OA displayed reduced ipsilateral weight bearing and hindpaw mechanical withdrawal
      thresholds, mild synovitis and increased TrkA expression in DRG. NGF injection
      into OA knees produced a prolonged augmentation of weight-bearing asymmetry,
      compared to NGF injection in non-osteoarthritic knees. However, hindpaw
      mechanical withdrawal thresholds were not further decreased by NGF. Pretreatment
      with indomethacin attenuated NGF-facilitated weight-bearing asymmetry and
      reversed OA-induced ipsilateral TrkA mRNA up-regulation. CONCLUSIONS: OA knees
      were more sensitive to NGF-induced pain behaviour compared to non-osteoarthritic
      knees. Cyclo-oxygenase products may contribute to increased TrkA expression
      during OA development, and the subsequent increased NGF sensitivity. Treatments
      that reduce sensitivity to NGF have potential to improve OA pain.

PMID- 23852766
TI  - First-trimester hyperglycosylated human chorionic gonadotropin and development of
      hypertension.
AB  - OBJECTIVE: This study aimed to determine whether urine levels of
      hyperglycosylated human chorionic gonadotropin (HhCG) in the first trimester are
      predictive of subsequent development of hypertension during pregnancy METHOD:
      This prospective cohort study consisted of women seeking care before 12 weeks
      gestation. A clean catch urine was obtained at the first prenatal visit and
      tested for HhCG and creatinine levels. The median HhCG levels and multiples of
      the median (MoM) by gestational age were compared between the groups that either
      developed hypertension or did not. RESULTS: Urine HhCG were determined for 204
      women between 4 weeks 4 days to 11 weeks 6 days. The median HhCG of those who
      developed gestational hypertension (n = 7) or preeclampsia (n = 15) did not
      differ from the group that did not (median: 284 ng/mg creatinine vs 365 ng/mg; p
      = 0.55). If the MoM of HhCG for the no hypertension group was 1.00, the MoM of
      HhCG for the hypertension group was 0.93 (p = 0.93). A possible association was
      observed after 10 weeks between low HhCG levels and the development of late-onset
      hypertension (>=34 weeks). CONCLUSIONS: Prenatal screening for subsequent
      hypertension is unreliable with a single measurement of maternal urine HhCG at 10
      weeks or less.

PMID- 23852765
TI  - Contribution of the COMT Val158Met variant to symptomatic knee osteoarthritis.

PMID- 23852768
TI  - Superatom networks in thiolate-protected gold nanoparticles.

PMID- 23852767
TI  - Evolving of therapeutic strategies for CNS-PNET.
AB  - BACKGROUND: A protocol for the intensive treatment of non-cerebellar PNET (CNS
      PNET) combining chemotherapy and radiotherapy was launched in 2000. Efforts were
      subsequently made to improve the prognosis and to de-escalate the treatment for
      selected patient groups. PROCEDURE: Twenty-eight consecutive patients were
      enrolled for a high-dose drug schedule (methotrexate, etoposide,
      cyclophosphamide, and carboplatin +/- vincristine), followed by hyperfractionated
      accelerated CSI (HART-CSI) at total doses of 31-39 Gy, depending on the patient's
      age, with two high-dose thiotepa courses following CSI. After the first 15
      patients had been treated, craniospinal irradiation (CSI) was replaced with focal
      radiotherapy (RT) for selected cases (non-metastatic and not progressing during
      induction chemotherapy). Eight of the 28 children received the same chemotherapy
      but conventionally fractionated focal RT at 54 Gy. RESULTS: The 5-year
      progression-free survival (PFS), event-free survival (EFS), and overall survival
      (OS) rates were 62%, 53%, and 52%, respectively, for the whole series, and 70%,
      70%, and 87% for the eight focally irradiated children. Residual disease and
      metastases were not prognostically significant. In children with residual
      disease, response to RT was significant (5-year PFS 59% vs. 20%, P = 0.01), while
      the total dose of CSI was not. There were three treatment-related toxic events.
      Relapses were local in seven cases (including two of the eight focally irradiated
      patients), and both local and disseminated in 2. CONCLUSIONS: This intensive
      schedule enabled treatment stratification for the purposes of radiation, thereby
      sparing some children full-dose CSI. Local control is the main goal of treatment
      for CNS-PNET.

PMID- 23852770
TI  - Prevalence and quantitation of adenovirus DNA from human tonsil and adenoid
      tissues.
AB  - In this study, real-time PCR was used to quantify adenovirus DNA in cell
      suspensions prepared from 106 right and left tonsils and 10 adenoids obtained
      from 57 patients who underwent routine tonsillectomies and/or adenoidectomies.
      Eighty-four (72.4%) tonsils and adenoids samples were positive for HAdV by real
      time PCR. The viral load ranged from 2.8 * 10(2) to 2.6 * 10(6) copies/10(7)
      cells and varied up to sixfold between the right and left tonsils. In some cases,
      only one tonsil was positive and the viral load was lower in older children.
      Seventy-eight of 84 positive samples could be typed by sequencing of the hexon L1
      region. Species C (types 1, 2, and 5) were detected in 84.1% of the patients
      followed by types 3 and 7 of species B (6.8%), HAdV-E4 (6.8%), and HAdV-F41
      (2.3%). In one patient adenovirus C2 was found in the left tonsil and adenovirus
      C5 in the right tonsil. No DNA methylation was detected in either the E1A
      promoter or the major late promoter region of adenovirus DNA from six tonsils and
      adenoids samples and two clinical isolates.

PMID- 23852771
TI  - Depiction of myocardial crypts in hypertrophic cardiomyopathy by cardiovascular
      MRI.

PMID- 23852769
TI  - Human epidermal receptor 2-amplified salivary duct carcinoma: regression with
      dual human epidermal receptor 2 inhibition and anti-vascular endothelial growth
      factor combination treatment.
AB  - BACKGROUND: Salivary ductal carcinoma is a rare cancer with poor prognosis and
      limited treatment options. Human epidermal receptor 2 (HER2)-directed treatment
      has been attempted in HER2-amplified or overexpressed salivary gland malignancies
      with limited success. METHODS: We report resolution of measurable disease and
      minimal residual disease in a patient with salivary duct cancer treated with
      trastuzumab, lapatinib, and bevacizumab, with treatment ongoing for more than 2
      years. RESULTS: This treatment has been tolerated well except for grade 2
      diarrhea and mucositis, which required a dose reduction of lapatinib to 1000 mg
      daily. The response observed was achieved in spite of receiving extensive prior
      therapy, including trastuzumab and/or chemotherapy for 20 months on which his
      tumors progressed. CONCLUSION: The combination of trastuzumab, lapatinib, and
      bevacizumab may warrant investigation as a non-cytotoxic alternative for
      treatment of HER2-amplified or overexpressed salivary duct carcinoma and other
      HER2-amplified or overexpressed salivary gland tumors, particularly those not
      responsive to trastuzumab monotherapy.

PMID- 23852772
TI  - Identifying protein complexes from heterogeneous biological data.
AB  - With the increasing availability of diverse biological information for proteins,
      integration of heterogeneous data becomes more useful for many problems in
      proteomics, such as annotating protein functions, predicting novel protein
      protein interactions and so on. In this paper, we present an integrative approach
      called InteHC (Integrative Hierarchical Clustering) to identify protein complexes
      from multiple data sources. Although integrating multiple sources could
      effectively improve the coverage of current insufficient protein interactome (the
      false negative issue), it could also introduce potential false-positive
      interactions that could hurt the performance of protein complex prediction. Our
      proposed InteHC method can effectively address these issues to facilitate
      accurate protein complex prediction and it is summarized into the following three
      steps. First, for each individual source/feature, InteHC computes the matrices to
      store the affinity scores between a protein pair that indicate their propensity
      to interact or co-complex relationship. Second, InteHC computes a final score
      matrix, which is the weighted sum of affinity scores from individual sources. In
      particular, the weights indicating the reliability of individual sources are
      learned from a supervised model (i.e., a linear ranking SVM). Finally, a
      hierarchical clustering algorithm is performed on the final score matrix to
      generate clusters as predicted protein complexes. In our experiments, we compared
      the results collected by our hierarchical clustering on each individual feature
      with those predicted by InteHC on the combined matrix. We observed that
      integration of heterogeneous data significantly benefits the identification of
      protein complexes. Moreover, a comprehensive comparison demonstrates that InteHC
      performs much better than 14 state-of-the-art approaches. All the experimental
      data and results can be downloaded from
      http://www.ntu.edu.sg/home/zhengjie/data/InteHC.

PMID- 23852773
TI  - Nucleotide-independent cytoskeletal scaffolds in bacteria.
AB  - Bacteria possess a diverse set of cytoskeletal proteins that mediate key cellular
      processes such as morphogenesis, cell division, DNA segregation, and motility.
      Similar to eukaryotic actin or tubulin, many of them require nucleotide binding
      and hydrolysis for proper polymerization and function. However, there is also a
      growing number of bacterial cytoskeletal elements that assemble in a nucleotide
      independent manner, including intermediate filament-like structures as well
      several classes of bacteria-specific polymers. The members of this group form
      stable scaffolds that have architectural roles or act as localization factors
      recruiting other proteins to distinct positions within the cell. Here, we
      highlight the elements that constitute the nucleotide-independent cytoskeleton of
      bacteria and discuss their biological functions in different species.

PMID- 23852774
TI  - Perioperative beta-blockade improves outcomes in higher risk patients following
      non-cardiac surgery.

PMID- 23852775
TI  - Oncolytic effects of parvovirus H-1 in medulloblastoma are associated with
      repression of master regulators of early neurogenesis.
AB  - Based on extensive pre-clinical studies, the oncolytic parvovirus H-1 (H-1PV) is
      currently applied to patients with recurrent glioblastoma in a phase I/IIa
      clinical trial (ParvOryx01, NCT01301430). Cure rates of about 40% in pediatric
      high-risk medulloblastoma (MB) patients also indicate the need of new therapeutic
      approaches. In order to prepare a future application of oncolytic
      parvovirotherapy to MB, the present study preclinically evaluates the cytotoxic
      efficacy of H-1PV on MB cells in vitro and characterizes cellular target genes
      involved in this effect. Six MB cell lines were analyzed by whole genome
      oligonucleotide microarrays after treatment and the results were matched to known
      molecular and cytogenetic risk factors. In contrast to non-transformed infant
      astrocytes and neurons, in five out of six MB cell lines lytic H-1PV infection
      and efficient viral replication could be demonstrated. The cytotoxic effects
      induced by H-1PV were observed at LD50s below 0.05 p. f. u. per cell indicating
      high susceptibility. Gene expression patterns in the responsive MB cell lines
      allowed the identification of candidate target genes mediating the cytotoxic
      effects of H-1PV. H-1PV induced down-regulation of key regulators of early
      neurogenesis shown to confer poor prognosis in MB such as ZIC1, FOXG1B, MYC, and
      NFIA. In MB cell lines with genomic amplification of MYC, expression of MYC was
      the single gene most significantly repressed after H-1PV infection. H-1PV
      virotherapy may be a promising treatment approach for MB since it targets genes
      of functional relevance and induces cell death at very low titers of input virus.

PMID- 23852777
TI  - Two-dimensional proteome reference map of Prototheca zopfii revealed reduced
      metabolism and enhanced signal transduction as adaptation to an infectious life
      style.
AB  - Biochemical, serological, and genetic analyses have identified two genotypes of
      Prototheca zopfii, a unicellular microalga belonging to the family Chlorellaceae.
      The P. zopfii genotype 1, abundantly present in cow barns and environment,
      remains nonpathogenic, while P. zopfii genotype 2 has been isolated from cows
      with bovine mastitis. The present study was carried out to identify the protein
      expression level difference between the pathogenic and nonpathogenic strains of
      P. zopfii. A total of 782 protein spots were observed on the 2D fluorescence
      difference gel electrophoresis (2D DIGE) gels among which 63 and 44 proteins were
      identified to be overexpressed in genotypes 1 and 2, respectively. The limited
      number of protein entries specific for Prototheca in public repositories resulted
      mainly in the identification of proteins described in other algae,
      microorganisms, or plants. Gene ontology (GO) analysis indicated reduced
      carbohydrate metabolism in genotype 1, while genotype 2 displayed enhanced DNA
      binding, kinase activity, and signal transduction. These effects point to
      metabolic and signaling adaptations in the pathogenic strain and provide insights
      into the evolution of otherwise highly similar strains. All MS data have been
      deposited in the ProteomeXchange with identifier PXD000126. 

PMID- 23852776
TI  - Development and assessment of a biodegradable solvent cast polyester fabric small
      diameter vascular graft.
AB  - Adjusting the mechanical properties of polyester-based vascular grafts is crucial
      to achieving long-term success in vivo. Although previous studies using a fabric
      based approach have achieved some success, a central issue with pure poly(lactic
      acid) (PLA) or poly(glycolic acid) (PGA) grafts sealed with poly(DL-caprolactone
      co-lactic acid) (P(CL/LA)) has been stenosis. Intimal hyperplasia, a leading
      cause of stenosis, can be caused by the mechanical incompatibility of synthetic
      vascular grafts. Investigating the performance of poly(glycolic-co-lactic acid)
      (PGLA) grafts could lead to insight into whether graft stenosis stems from
      mechanical issues such as noncompliance and unfavorable degradation times. This
      could be achieved by examining grafts with tunable mechanical properties between
      the ranges of such properties in pure PGA and PLA-based grafts. In this study, we
      examined PGLA-based grafts sealed with different P(CL/LA) solutions to determine
      the PGLA-P(CL/LA) grafts' mechanical properties and tissue functionality. Cell
      attachment and proliferation on graft surfaces were also observed. For in vivo
      assessment, grafts were implanted in a mouse model. Mechanical properties and
      degradation times appeared adequate compared to recorded values of vessels used
      in autograft procedures. Initial neotissue formation was observed in the grafts
      and patency maintained during the pilot study. This study presents a ~1-mm
      diameter degradable graft demonstrating suitable mechanical properties and in
      vivo pilot study success, enabling further investigation into the tuning of
      mechanical properties to reduce complications in degradable polyester fabric
      based vascular grafts.

PMID- 23852778
TI  - [Pilot project of a pediatric antibiotic stewardship initiative at the Hauner
      children's hospital].
AB  - The steady increase in antimicrobial resistance is of growing concern in
      healthcare. Antibiotic Stewardship [ABS] Strategies are important tools to
      control antibiotic use and -prevent antimicrobial resistance. An increasing
      number of institutions are developing ABS initiatives also in pediatrics.
      However, few data are available assessing the implementation and efficiency of
      these pediatric ABS programs.At the Dr. von Hauner Children's Hospital, Ludwig
      Maximilian University, a tertiary care pediatric reference center, a pediatric
      ABS Team has been implemented. Key structural elements were the same as for adult
      patients, but antimicrobials agents selected for monitoring and appropriate
      clinical endpoints are different in pediatrics.Key features were: 1. prospective
      audit with feedback and formulary restriction and 2. pre-authorization (also
      referred to as prior approval). The ABS team consisted of one pediatric
      infectious disease specialist, one clinical fellow in pediatric infectious
      diseases, and one clinical pharmacist with training in infectious diseases.With
      the implementation of a pediatric ABS strategy we could significantly influence
      antimicrobial consumption in our hospital. Cost-savings are estimated to be above
      330 000 ? per year, and concomitantly the use of broad-spectrum antibiotics and
      antifungal compounds was significantly reduced.Antibiotic Stewardship [ABS]
      Strategies may be an effective tool to control antibiotic use in the setting of a
      large tertiary pediatric teaching hospital. A national guideline for ABS
      initiatives may help to further improve rational use of antibiotics in the
      hospital setting.

PMID- 23852779
TI  - A conformationally flexible dinuclear Pt(II) complex with differential behavior
      of its two states toward quadruplex DNA.
AB  - The reaction of tetrakis(pyridine-2-yl)pyrazine (tppz) with 2 equiv of (2,2'
      bpy)Pt(II) in water yields two isomeric dinuclear cations, [{Pt(2,2'-bpy)}2
      (tppz)](4+) , in which Pt coordination exclusively takes place through the two
      pairs of pyridine-2-yl nitrogen atoms. The two conformational isomers differ in
      their overall shape, with the formation of "Z" and "U" shapes, which are formed
      at 40  degrees C (Z isomer, 1) and under reflux conditions (U isomer, 2),
      respectively. X-ray crystal-structure analyses of the Z isomer, [{Pt(2,2'-bpy)}2
      (tppz)](PF6 )4 ?3 CHCl3 ?4 H2 O (1 a), and of the U isomer, [{Pt(2,2'-bpy)}2
      ](PF6 )4 ?2 CH3 CN?1.5 H2 O (2 a), were carried out. Co-crystallization of
      compound 2 with PtCl2 (2,2'-bpy) yielded [{Pt(2,2'-bpy)}2 (tppz)](BF4 )4 ?[PtCl2
      (2,2'-bpy)]?4.5 H2 O (3), in which the PtCl2 (2,2'-bpy) entity was sandwiched
      between the two 2,2'-bpy faces of the U-shaped cation (2). Quantum chemical
      calculations revealed that the U isomer was more stable than the Z isomer, both
      in the gas phase and in an aqueous environment. These two isomers display
      different affinities toward duplex DNA and human telomeric quadruplex DNA
      (Htelo), as concluded from CD spectroscopy and FID assays. Thus, the U isomer
      binds significantly more strongly to quadruplex DNA (DC50 =0.38 MUM) than the Z
      isomer (DC50 =8.50 MUM). 

PMID- 23852780
TI  - Circulating level of lipocalin 2 as a predictor of severity in patients with
      community-acquired pneumonia.
AB  - BACKGROUND: The aim of this study was to investigate the differential plasma
      levels of lipocalin 2 (LCN2) and its complex with MMP-9 (where MMP is matrix
      metalloproteinase) before and after antibiotic treatment in hospitalized adult
      patients with community-acquired pneumonia (CAP). METHOD: Plasma LCN2 and
      LCN2/MMP-9 complex levels were measured in 61 adult patients with CAP and 60
      healthy controls using commercial enzyme-linked immunosorbent assay (ELISA).
      RESULTS: A decrease in the number of white blood cells (WBCs) and neutrophils and
      decreases in the levels of C-reactive protein (CRP), LCN2, and LCN2/MMP-9 complex
      were observed after antibiotic treatment. The plasma level of LCN2, but not that
      of CRP, was correlated with the severity of CAP based on the Pneumonia Severity
      Index (PSI; r = 0.333, P = 0.009), confusion, urea, respiratory rate and blood
      pressure (CURB)-65 (r = 0.288, P = 0.024), and Acute Physiology And Chronic
      Health Evaluation II (APACHE II) scores (r = 0.328, P = 0.010). LCN2 levels were
      also significantly correlated with LCN2/MMP-9 levels and the numbers of WBCs or
      neutrophils. CONCLUSIONS: Plasma levels of LCN2 and the LCN2/MMP-9 complex can
      act as adjuvant diagnostic biomarkers for CAP. Plasma LCN2 might play a further
      role in the clinical assessment of the severity of CAP, which could potentially
      guide the development of future treatment strategies.

PMID- 23852781
TI  - Determination of storage time of saliva samples obtained from patients with and
      without chronic periodontitis for the comparison of some biochemical and
      cytological parameters.
AB  - BACKGROUND: Salivary glutathione (GSH), malondialdehyde (MDA), protein, sialic
      acid (SA) levels, cytological parameters, and tissue factor activities (TFa) were
      investigated when fresh and after 3, 7, 11, 15, 21, and 30 days (d) of storage at
      -20 degrees C both in the control and the periodontitis group. Moreover, the
      control and the periodontits groups were compared and continuity of the
      significances detected between the two groups were evaluated. METHODS: GSH, MDA,
      SA, protein, and TFa were determined using the methods of Beutler, Yagi, Warren,
      Lowry, and Quick, respectively. Saliva imprint samples were stained with Giemsa
      and microscopically examined. RESULTS: When the continuity of the significances
      of differences between the two groups was investigated, differences continued to
      be significant for GSH and TFa on days 3, 7, 11, 15, 21, and 30. Cytologically,
      only the significance detected between leucocyte numbers continued to be
      significant for 30 d. However significance of differences in total protein, MDA,
      and SA levels on day 0, were interrupted on days 3, 7, and 11, respectively.
      CONCLUSION: Saliva samples may be stored for 30 d for GSH and TFa analyses in
      patients with and without periodontitis. However, to compare salivary MDA, SA,
      and total protein levels in these groups we suggest fresh samples to be studied.

PMID- 23852782
TI  - Analysis of beta/alpha globin ratio by using relative qRT-PCR for diagnosis of
      beta-thalassemia carriers.
AB  - BACKGROUND: Current routine tests for premarital screening of beta-thalassemia
      carriers are not applicable for diagnosis of rare atypical minor beta-thalassemia
      cases. A more specialized laboratory evaluation for them is the measurement of
      beta/alpha chain synthesis ratio with the assistance of radioactive amino acids.
      This method is also no longer routinely accessible. Consequently it is required
      to establish a rapid, trouble-free, and reliable method that encompasses all the
      cases of beta-thalassemia carriers. Therefore we have determined beta/alpha
      globin mRNA ratio by applying relative qRT-PCR in various beta-thalassemia
      patients. METHODS: Reticulocytes RNA extraction and subsequent cDNA synthesis
      were performed, followed by relative qRT-PCR for alpha- and beta-globin chain
      genes and beta-actin gene as an endogenous reference. beta/alpha-Globin gene
      ratio was then evaluated with the Pfaffl method. RESULTS: The mean of beta/alpha
      ratio was 0.99, 0.81, 0.69, and 0.69 for normal population, minor, intermediate,
      and major beta-thalassemia, respectively. Approximately 6% of cases with minor
      thalassemia RBC index and normal HbA2 and having a decreased beta/alpha ratio
      were located in the minor beta-thalassemia group. The mean of beta/alpha mRNA
      ratio in normal individuals and minor beta-thalassemia was significantly
      different with all other groups (P-value < 0.05). Nevertheless, there was no such
      association between beta/alpha mRNA ratio in major and intermediate beta
      thalassemia. CONCLUSION: According to the significant differences achieved, no
      overlapping between minor beta-thalassemia and normal group, capability of
      diagnosing atypical minor beta-thalassemia, and accessibility of this technique,
      we can declare that this method could be suggested as a routine premarital
      screening test for beta-thalassemia carriers.

PMID- 23852783
TI  - Evaluation of in-house loop-mediated isothermal amplification (LAMP) assay for
      rapid diagnosis of M. tuberculosis in pulmonary specimens.
AB  - BACKGROUND: Loop-mediated isothermal amplification (LAMP) assay has come forward
      as a rapid, cost-effective molecular technique for diagnosis of tuberculosis (TB)
      in developing countries. This study evaluated Mycobacterium tuberculosis-specific
      in-house LAMP assay targeting 16s rRNA and compared it with other conventional
      tests and nucleic acid amplification assay (IS6110 PCR). METHODS: A total of 133
      sputum specimens (103 from suspected pulmonary TB cases and 30 from non-TB
      controls) were subjected to conventional tests, IS6110 PCR and 16s rRNA LAMP
      assay. RESULTS: Of the 103 patients, the maximum number of cases were found to be
      positive by LAMP assay, that is, in 87 (84.5%) patients, followed by culture
      positive in 78 (75.7%), IS6110 PCR in 74 (71.8%), and smear positive in 70
      (67.9%) patients. Of the 83 smear positive and/or culture positive cases, LAMP
      detected 77 (92.77%) cases, and was found to be superior to IS6110 PCR, which
      could detect 69 (83.1%) cases; a concordance of 0.6 was obtained between the two
      tests using kappa statistics. CONCLUSION: Overall, LAMP was simple and
      efficacious for early diagnosis of smear positive, culture positive cases as well
      as for confirmation of smear negative, culture negative cases, and was found to
      be superior to IS6110 PCR.

PMID- 23852784
TI  - A novel immunoassay for the quantization of CYFRA 21-1 in human serum.
AB  - BACKGROUND: Cytokeratin 19 fragment antigen (CYFRA 21-1) is used to diagnose and
      monitor neoplasms. However, the main disadvantages of the currently available
      CYFRA 21-1 assays include heterogenous technology, being time-consuming, and
      having low through-put with low insensitivity. This study investigated the use of
      amplified luminescent proximity homogeneous immunoassay (AlphaLISA) for the
      quantization of CYFRA 21-1 in human serum. METHODS: The AlphaLISA kit was
      developed based on AlphaScreen detection technology with two different anti-CYFRA
      21-1 monoclonal antibodies. One was coated on AlphaLISA acceptor beads and the
      other was biotinylated. Donor beads were coated with streptavidin. The test
      conditions were optimized and analytical performance was studied. RESULTS: The
      measurement range of AlphaLISA CYFRA 21-1 kit was 0.08-500 ng/ml. Assay detection
      limit was 0.08 ng/ml. The intra- and interassay coefficients of variation were
      3.00-9.00% and 4.00-10.00%, respectively. There was no cross-reaction to alpha
      fetoprotein (AFP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE),
      cancer antigen 19-9 (CA19-9), cytokeratins 8 (CK8), and cytokeratins 18 (CK18).
      The correlation coefficient of blood samples involved was 0.974 between CYFRA 21
      1-AlphaLISA assay and a commercial electrochemiluminescence immunoassay (ECLIA)
      CYFRA 21-1 kit (Roche). CONCLUSIONS: The AlphaLISA CYFRA 21-1 kit developed in
      this study had favorable performance characteristics for clinical application
      with acceptable analytical sensitivity, specificity, and accuracy.

PMID- 23852785
TI  - Measurement of serum total vitamin D (25-OH) using automated immunoassay in
      comparison [corrected] with liquid chromatography tandem-mass spectrometry.
AB  - BACKGROUND: The associations of vitamin D deficiency with many nonskeletal
      diseases are still being discovered. We evaluated the use of an automated
      immunoassay to measure serum total vitamin D (25-OH) and assessed vitamin D
      status in a Korean adult population. METHODS: We compared the Elecsys Vitamin D
      (25-OH) Total Assay (Roche Diagnostics) with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) using 300 serum samples. Total imprecision was calculated
      using three levels of quality control materials and serum samples. We also
      investigated the vitamin D status using data for 70,762 cases who had a routine
      health check-up in our hospitals. RESULTS: The regression equation: Elecsys =
      0.882 * LC-MS/MS + 6.814 (r = 0.926). Total imprecision was within 10% for all
      quality control materials and serum samples. The prevalence of vitamin D
      deficiency using cut-off values of <50 nmol/l (<20 ng/ml) were 70.3% in males and
      86.4% in females, respectively. The prevalence of vitamin D deficiency was higher
      in younger subjects than in older subjects (P for linear-by-linear association
      was <0.001). Serum vitamin D levels were highest in September and lowest in
      February. CONCLUSION: The Elecsys Vitamin D (25-OH) Total Assay was comparable to
      LC-MS/MS and appropriate for routine clinical use. Vitamin D deficiency is common
      in Korean adults.

PMID- 23852786
TI  - Mathematical equations to calculate true mycophenolic acid concentration in human
      plasma by using two immunoassays with different cross-reactivities with acyl
      glucuronide metabolite: comparison of calculated values with values obtained by
      using an HPLC-UV method.
AB  - BACKGROUND: Both immunoassays and chromatographic methods are available for
      therapeutic drug monitoring of mycophenolic acid (MPA). Although chromatographic
      methods are more precise, immunoassays are widely used in clinical laboratories
      due to ease of adopting such assays on automated analyzers. We studied the
      possibility of using mathematical equations to calculate true MPA concentration
      by accounting for acyl glucuronide cross-reactivities with immunoassays by using
      two immunoassays with widely different cross-reactivities with the metabolite.
      METHODS: We determined MPA concentrations in 20 specimens obtained from
      transplant recipients using cloned enzyme donor immunoassay (CEDIA) assay and a
      new particle enhanced turbidimetric inhibition immunoassay (PETINIA) assay. Then
      we developed mathematical equations to calculate true MPA concentration using
      values obtained by both immunoassays and reported cross-reactivity of acyl
      glucuronide with respective immunoassays. Calculated concentrations were compared
      with values obtained by using a high-performance liquid chromatography combined
      with ultraviolet detection (HPLC-UV) method. RESULTS: We obtained good
      correlation between calculated MPA concentrations and corresponding MPA level
      obtained by using HPLC-UV method. Using x-axis as the MPA concentrations
      determined by the HPLC-UV method and y-axis as the calculated MPA level, we
      observed the following regression equation: y = 1.083x - 0.0995 (r = 0.99, n =
      20). CONCLUSIONS: Mathematical equations can be used to calculate true MPA
      concentrations using two immunoassays with different cross-reactivities with acyl
      glucuronide metabolite.

PMID- 23852787
TI  - Brief communication: comparison the diagnostic performance of four HBsAg ELISA
      kits.
AB  - BACKGROUND: Comparison of diagnostic efficiency of four ELISA kits for
      determining HBsAg. METHODS: Collecting 348 serum samples from clinical laboratory
      of Renmin Hospital of Wuhan University without specific gender and age
      requirements, determining HBsAg by the four ELISA kits, simultaneously.
      Confirmatory test was carried out when the initial results are positive. RESULTS:
      329 out of 348 samples results were consistent (94.5%), 152 out of 329 were
      positive, and 177 out of 329 were negative, and all the positive results can be
      confirmed; 19 samples were not consistent (5.5%), and only 1 sample was confirmed
      by the confirmatory test. After calculation, the diagnostic efficiencies of the
      four ELISA kits (Beijing Wantai, Xiamen Xinchuang, Zhuhai Lizhu, and Shanghai
      Kehua) were 98.6%, 98.0%, 99.7%, and 97.4%, respectively, the sensitivities were
      100%, 99.4%, 99.4%, and 100%, respectively, the specificities were 97.5%, 96.9%,
      100%, and 95.4%, respectively, the false positive rates were 2.5%, 3.1%, 0, and
      4.6%, respectively, and the false negative rates were 0, 0.6%, 0.6%, and 0,
      respectively. All the initial absorbencies of the false positive samples were
      less than 1.0. CONCLUSION: The diagnostic efficiency of Lizhu is the highest,
      while Kehua is the lowest. False positive or false negative results would take
      place in any of the kits, an HBsAg confirmatory test is essential for initially
      positive samples, especially with absorbance <1.0, because it can exclude most
      false positives.

PMID- 23852788
TI  - PDE4D gene polymorphisms and coronary heart disease: a case-control study in a
      north Indian population.
AB  - BACKGROUND: The present study aims to assess the association of PDE4D gene
      polymorphisms (SNP83 and SNP87) with Coronary Heart Disease (CHD) in a single
      Mendelian population of Delhi. METHODS: A cross-sectional study was carried out
      wherein intravenous blood samples were collected from 100 cases and 100 age, sex
      and ethnicity matched controls along with their demographic, life style, and
      clinical profiles. RESULTS: Genotypic frequencies of PDE4D gene variants 83 and
      87 did not differ significantly between cases and controls. Odds ratio revealed a
      1.4-fold increased risk with PDE4D 83 C allele; though not significant. Both the
      SNPs showed significant association with serum triglyceride (TG) (P <= 0.05). A
      significant linkage disequilibrium was observed between the SNPs. The haplotype
      with mutant alleles of the two SNPs showed fivefold increased risk (though not
      significant) and that with normal allele of SNP 83 and mutant allele of SNP 87 (T
      T) was found to be significantly associated with the disease in the present
      population. CONCLUSIONS: PDE4D gene variants 83 and 87 did not show any
      significant association with CHD. However, their interaction with TG and the
      haplotypic association found in the present population is indicative of the
      population-specific risk associated with CHD where majority of the individuals
      have high cholesterol and high Body Mass Index (BMI).

PMID- 23852789
TI  - Vitamin D and its relationship with markers of bone metabolism in healthy Asian
      women.
AB  - BACKGROUND: In this study, we aimed to determine the normal ranges of 25-hydroxy
      vitamin D(3) (25-OHD(3)), parathyroid hormone (PTH), and the markers of bone
      turnover, procollagen type 1 N propeptide (P1NP) and C-terminal cross-linked
      telopeptide of type 1 collagen (CTX), in normal healthy women in Singapore, and
      to explore the relationship between vitamin D, PTH, and these markers of bone
      turnover in the women. METHODS: One hundred and ninety-seven healthy women, aged
      25 to 60, were selected from a hospital staff health screening program; 68% were
      Chinese, 18% Malay, and 14% Indian. P1NP, CTX, and 25-OHD(3) were measured using
      the Roche Cobas(r) electrochemiluminescence immunoassay. Serum PTH was measured
      using the Siemens ADVIA Centaur(r) immunoassay. RESULTS: Sixty-five percent had
      25-OHD(3) concentrations <50 nmol/l. Vitamin D insufficiency (25-OHD(3) < 50
      nmol/l) was more prevalent in Malays (89%) and Indians (82%) compared to Chinese
      (56%). There was no correlation between vitamin D and age. PTH positively
      correlated with age, and Malays and Indians had higher PTH concentrations than
      Chinese. There was an inverse correlation between PTH and 25-OHD(3), but no
      threshold of 25-OHD(3) concentrations at which PTH plateaued. The bone turnover
      markers P1NP and CTX inversely correlated with age but were not different between
      ethnic groups. CTX and P1NP exhibited good correlation, however, there was no
      significant correlation between 25-OHD(3) or PTH concentrations and the bone
      turnover markers P1NP and CTX. CONCLUSIONS: Healthy women in Singapore have a
      high prevalence of vitamin D insufficiency. Vitamin D insufficiency was more
      prevalent in Malays and Indians compared to Chinese.

PMID- 23852790
TI  - A new blood collection device minimizes cellular DNA release during sample
      storage and shipping when compared to a standard device.
AB  - BACKGROUND: Cell-free DNA (cfDNA) circulating in blood is currently used for
      noninvasive diagnostic and prognostic tests. Minimizing background DNA is vital
      for detection of low abundance cfDNA. We investigated whether a new blood
      collection device could reduce background levels of genomic DNA (gDNA) in plasma
      compared to K(3) EDTA tubes, when subjected to conditions that may occur during
      sample storage and shipping. METHODS: Blood samples were drawn from healthy
      donors into K(3) EDTA and Cell-Free DNATM BCT (BCT). To simulate shipping,
      samples were shaken or left unshaken. In a shipping study, samples were shipped
      or not shipped. To assess temperature variations, samples were incubated at 6
      degrees C, 22 degrees C, and 37 degrees C. In all cases, plasma was harvested by
      centrifugation and total plasma DNA (pDNA) assayed by quantitative real-time
      polymerase chain reaction (qPCR). RESULTS: Shaking and shipping blood in K(3)
      EDTA tubes showed significant increases in pDNA, whereas no change was seen in
      BCTs. Blood in K(3) EDTA tubes incubated at 6 degrees C, 22 degrees C, and 37
      degrees C showed increases in pDNA while pDNA from BCTs remained stable.
      CONCLUSIONS: BCTs prevent increases in gDNA levels that can occur during sample
      storage and shipping. This new device permits low abundance DNA target detection
      and allows accurate cfDNA concentrations.

PMID- 23852791
TI  - Comparison of fully automated urine sediment analyzers H800-FUS100 and LabUMat
      UriSed with manual microscopy.
AB  - BACKGROUND: Recent technical developments have focused on the full automation of
      urinalyses, however the manual microscopic analysis of urine sediment is
      considered the reference method. The aim of this study was to compare the
      performances of the LabUMat-UriSed and the H800-FUS100 with manual microscopy,
      and with each other. METHODS: The urine sediments of 332 urine samples were
      examined by these two devices (LabUMat-UriSed, H800-FUS100) and manual
      microscopy. RESULTS: The reproducibility of the analyzers, UriSed and Fus100 (4.1
      28.5% and 4.7-21.2%, respectively), was better than that with manual microscopy
      (8.5-33.3%). The UriSed was more sensitive for leukocytes (82%), while the Fus
      100 was more sensitive for erythrocyte cell counting (73%). There were moderate
      correlations between manual microscopy and the two devices, UriSed and Fus100,
      for erythrocyte (r = 0.496 and 0.498, respectively) and leukocyte (r = 0.597 and
      0.599, respectively) cell counting however the correlation between the two
      devices was much better for erythrocyte (r = 0.643) and for leukocyte (r = 0.767)
      cell counting. CONCLUSION: It can be concluded that these two devices showed
      similar performances. They were time-saving and standardized techniques,
      especially for reducing preanalytical errors such as the study time,
      centrifugation, and specimen volume for sedimentary analysis; however, the
      automated systems are still inadequate for classifying the cells that are present
      in pathological urine specimens.

PMID- 23852792
TI  - The relationship between serum fetuin-A, cystatin-C levels, and microalbuminuria
      in patients with metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome, syndrome X, is a group of metabolic disorders
      in which insulin resistance plays a pivotal role. The MS is an important risk
      factor for subsequent development of type 2 diabetes and cardiovascular disease.
      Fetuin-A is a liver derived blood protein that acts as effective inhibitor of
      soft tissue calcification. Cystatin C is a useful marker in measuring glomerular
      filtration rate. Moreover, recently it has been suggested that cystatin C may be
      a potential biomarker for detecting microalbuminuria. Microalbuminuria (MA) is a
      strong indicator of morbidity related to cardiovascular disorders, and is
      currently considered a novel diagnostic criterion for MS. It has been also
      demonstrated that the increased serum fetuin-A levels is associated with several
      parameters of MS. In this study, we attempted to investigate the relationship
      between serum fetuin-A, cystatin-C levels and microalbuminuria in patients with
      MS. METHODS: A total of 50 patients with MS and 25 control were included in this
      study. We defined MS by the NCEP criteria among nondiabetic outpatients. Patients
      with MS were further divided into two groups based on MA status. Overall 25 of
      the participants with MS did not have MA (group I), while the remaining 25 had MA
      (group II). None of the subjects in the healthy control group (group III) had
      laboratory findings supporting the presence of MA. The serum fetuin-A and
      cystatin-C levels were measured using ELISA. RESULTS: Age, distributions of sex,
      BP and LDL cholesterol levels were similar among all groups. BMI, Waist/hip
      ratio, FBG, HOMA-IR, total cholesterol, trigliserid, CRP levels were
      significantly higher in group I and group II compared to control. In group II,
      the cystatin-C and fetuin levels were higher than control. While the cystatin-C
      levels were higher in group II compared to group I, the fetuin levels did not
      different. Morever, the fetuin A and cystatin-C concentrations were positively
      correlated with microalbuminuria (r = 0.26, p = 0.02; r = 0.50, p = 0.0001,
      respectively). CONCLUSION: In our study, we found that MS patients with
      microalbuminuria had high levels of fetuin-A and cystatin-C. In conclusion, we
      suggest that determination of fetuin-A and cystatin C levels could be useful
      marker as an early indicator of renal injury in patients with MS.

PMID- 23852793
TI  - Association of tyrosyl-DNA phosphodiesterase 1 polymorphism with Tourette
      syndrome in Taiwanese patients.
AB  - BACKGROUND: Genetic, environmental, immunological, and hormonal factors
      contribute to the etiology of Tourette syndrome (TS). From the genetic
      standpoint, TS is a heterogeneous disorder. In our previous study, we found that
      a single nucleotide polymorphism (SNP) of x-ray repair cross-complementing group
      1 (XRCC1), a DNA repair gene, was associated with TS. Previous studies also
      showed that tyrosyl-DNA phosphodiesterase 1 (TDP1) interacts with XRCC1 to repair
      damaged DNA. However, the relationship between TS and SNPs of TDP1 gene is
      unknown. Therefore, the aim of this study was to test the hypothesis that if the
      TDP1 SNP, rs28365054 (c.400G>A, Ala134Thr), was associated with TS or not.
      METHODS: A case-control study was designed to test the hypothesis. A total of 122
      TS children and 106 normal children participated in the study. We used polymerase
      chain reaction to identify the SNP, rs28365054, of the TDP1 gene in the TS
      patients and the normal children. RESULTS: A polymorphism at position rs28365054
      in the TDP1 gene had a significant difference (P < 0.05) in the genotype
      distributions between the TS patients and the control group. The AG genotype was
      a risk factor for TS with an odds ratio of 2.26 for the AG versus AA genotype
      (95% CI 1.08-4.72). CONCLUSION: The findings of this study suggested that
      variants in the TDP1 gene might play a role in TS susceptibility.

PMID- 23852794
TI  - Reduced plasma citrulline levels in low birth weight infants with necrotizing
      enterocolitis.
AB  - BACKGROUND: Citrulline, a nonprotein amino acid, is an intermediate of the urea
      cycle and synthesized in small intestine. Lower plasma citrulline levels were
      associated with reduced function of enterocytes. Necrotizing enterocolitis (NEC)
      causes high morbidity and mortality, and leads impaired intestinal functions.
      METHODS: Plasma citrulline levels of neonates with a gestational age <32 weeks
      and <=1,500 gm who developed NEC stage II/III were measured by high-performance
      liquid chromatography. RESULTS: We enrolled 36 preterm infants including 20 with
      NEC and 16 controls. Median citrulline levels of NEC and control groups were 8.6
      and 20.18 MUmol/l (P < 0.05), and cut off level of citrulline was 13.15 MUmol/l
      with a sensitivity of 80% and a specificity of 82%. Median arginine levels of NEC
      and control groups were 22.02 and 39.89 MUmol/l (P < 0.05), and cut off level of
      arginine was 28.52 MUmol/l with a sensitivity of 70% and a specificity of 75%.
      Blood sampling day, gender, parenteral, and enteral nutrition did not affect the
      amino acid levels. CONCLUSION: We found lower plasma citrulline and arginine
      levels in preterm infants with NEC. Further studies are needed to determine most
      appropriate levels to predict recovery and prognosis of NEC, and treatment
      options with these amino acids in preterm infants.

PMID- 23852795
TI  - Usefulness of HPLC assay for early detection of microalbuminuria in chronic
      kidney disease.
AB  - BACKGROUND: Since the degree and increase of albuminuria predict cardiovascular
      and renal diseases even within the range of normoalbuminuria. The high
      performance liquid chromatography (HPLC) assay has been reported as a useful tool
      for earlier detection of microalbuminuria than turbidimetric immunoassay (TIA) in
      diabetes but has not been evaluated for other common diseases that caused chronic
      kidney disease (CKD). METHODS: We measured albumin in spot urine by TIA and HPLC
      assay in 119 patients with diabetes, hypertension, IgA nephropathy in complete
      remission, or autosomal-dominant polycystic kidney disease whose dipstick
      screening tests were negative. RESULTS: There were significant correlations (r =
      0.946) between TIA and HPLC assay, and the ratios of urine albumin/creatinine
      (ACR) measured by HPLC assay were always higher than those measured by TIA. The
      value of microalbuminuria was highest in IgA nephropathy patients, and higher in
      diabetic patients with hypertension than in those without hypertension. Fifty-one
      patients were classified as having normoalbuminuria and 42 as having
      microalbuminuria by both TIA and HPLC assay. However, 26 patients (21.8%) were
      classified having as normoalbuminuria by TIA but microalbumnuria by HPLC assay.
      Three of these patients were reclassified as microalbuminuria by both assays
      within 1 year. CONCLUSION: These results suggest that ACR measurements by HPLC
      assay are better than TIA for early detection and monitoring of microalbuminuria
      in patients with diabetes and hypertension.

PMID- 23852797
TI  - Assessment of factors influencing the Agrobacterium-mediated in planta seed
      transformation of brinjal (Solanum melongena L.).
AB  - An efficient and reproducible in planta transformation method was developed for
      brinjal using seed as an explant. The brinjal seeds were infected with
      Agrobacterium tumefaciens EHA 105 harbouring pCAMBIA 1301-bar plasmid, and the
      transformants were selected against BASTA(r). Several parameters influencing the
      in planta seed transformation such as pre-culture duration, acetosyringone
      concentration, surfactants, duration of sonication, vacuum pressure and vacuum
      duration have been evaluated. The putatively transformed (T 0) brinjal plants
      were screened by GUS histochemical analysis. Among the different combinations and
      concentrations tested, when the 18-h pre-cultured brinjal seeds were sonicated
      for 20 min and vacuum infiltered for 3 min at 500 mm of Hg in Agrobacterium
      suspension containing 100 MUM acetosyringone, 0.2 % Silwett L-77 favoured the
      Agrobacterium infection and showed maximum transformation efficiency. Among the
      five brinjal varieties evaluated, Arka Samhitha showed maximum transformation
      efficiency at 45.66 %. The transgene was successfully transmitted to progeny
      plants (T 1) which was evidenced by GUS histochemical analysis, polymerase chain
      reaction and Southern hybridisation. The in planta protocol developed in the
      present study would be beneficial to transfer the economically and nutritionally
      important genes into different varieties of brinjal, and the transgenic brinjal
      plants can be produced in less time (approximately 27 days). 

PMID- 23852798
TI  - Screening of tea (Camellia sinensis) for trait-associated molecular markers.
AB  - This study was done to identify random amplified polymorphic DNA (RAPD) markers
      that may associate with seven important traits in tea. Sixty RAPD primers were
      first screened using 18 cultivars under each of the 7 traits, followed by
      confirmatory screening of 20 promising primers with 32 tea cultivars. Six RAPD
      primers generated a total of nine specific bands that associated with six desired
      traits: black tea quality and tolerance to drought, high temperature, low
      temperature, Phomopsis theae, and high yield. These markers would allow early
      identification of plant material with the desired traits that can be advanced to
      the next stage of selection and enhance targeted choice of breeding stocks with
      the desirable traits. The nine RAPD markers identified in this study could
      improve precision and efficiency in tea breeding and selection and are an
      important contribution towards the establishment of marker-assisted selection in
      tea breeding programmes. 

PMID- 23852800
TI  - RE: Repeating blood cultures in neutropenic children with persistent fevers when
      the initial blood culture is negative.

PMID- 23852801
TI  - A meshless boundary method for Stokes flows with particles: application to
      canalithiasis.
AB  - We propose to couple the method of fundamental solutions (MFS) to the force
      coupling method (FCM). The resulting method is an efficient, easy to program,
      meshless method for flows at low Reynolds numbers with finite-size particles. In
      such an approach, the flow domain is extended across the solid particle phase,
      and the flow is approximated by a superposition of singular Stokeslets positioned
      outside the flow domain and finite-size multipoles collocated with the particle.
      To improve the efficiency of the coupling, we propose new MFS quadratures for the
      computation of the volume integrals required for the FCM. These are exact and do
      not require the expensive evaluation of Stokeslets. The proposed method has been
      developed in the context of investigations of the fluid dynamics of
      canalithiasis, that is, a pathological condition of the semicircular canals of
      the inner ear. Numerical examples are presented to illustrate the applicability
      of the method.

PMID- 23852799
TI  - Mutation frequency in 15 common cancer genes in high-risk head and neck squamous
      cell carcinoma.
AB  - BACKGROUND: With prior studies having looked at unselected cohorts, we sought to
      explore the mutational landscape in a high-risk group of head and neck squamous
      cell carcinoma (HNSCC) tumors. METHODS: A multiplexed polymerase chain reaction
      (PCR) assay evaluating 68 loci in 15 genes was performed on 64 patients with high
      risk HNSCC. Because of the frequent PIK3CA and AKT1 mutations in patients with
      oropharyngeal carcinoma, we evaluated the relationship between mutation status
      and both clinical/pathologic variables and tumor control in this subgroup.
      RESULTS: Seventeen of 64 patients harbored mutations in the assayed loci: 16% in
      PIK3CA, 9% in TP53, 2% in AKT1, and 2% in epidermal growth factor receptor
      (EGFR). The frequency of PIK3CA/AKT1 mutations in oropharyngeal and sinonasal
      primaries was increased compared to other primary sites (35% vs 6%; p = .005).
      There was no relationship between mutation status and overall survival (OS),
      disease-specific death, or progression in the oropharyngeal cohort. CONCLUSION:
      We identified frequent PIK3CA mutations in patients with high-risk HNSCC confined
      predominantly to the oropharyngeal and sinonasal subsites; for the first time,
      mutation in AKT1 has been identified in HNSCC.

PMID- 23852802
TI  - Role of norovirus in acute gastroenteritis in the Northwest of Spain during 2010
      2011.
AB  - A total of 2,643 samples from patients with gastroenteritis in Galicia (NW Spain)
      were tested for the presence of Norovirus (NoV). NoV genogroup GI was detected in
      416 (15.7%) samples, while NoV genogroup GII was detected in 278 (10.5%) samples.
      Mixed infections of NoV GI and GII were observed in 53 (2%) samples. Total
      prevalence of NoV in the analyzed samples was 28.3%. Besides NoV diagnosis assay,
      all the specimens were also submitted to routine clinical bacteriology tests.
      Cryptosporidium spp. as well as adenovirus (AdV) and rotavirus (RV) were
      determined on some samples after specific request by hospital units. The results
      obtained allowed to determine the disease etiology in 14.4% of the patients.
      Taking into account all the microorganisms studied, the etiological agent was
      determined for 39.5% of the cases. The results indicated that NoVs are the
      leading cause of acute gastroenteritis in all age-groups in Northwestern Spain,
      and that the lack of routine NoV diagnosis contributes to the underestimation of
      the importance of this virus, not only in outbreaks, but also in sporadic cases
      of acute gastroenteritis.

PMID- 23852803
TI  - Percutaneous closure of pseudoaneurysm of common iliac artery with amplatzer duct
      occluder II.
AB  - Seven-year-old boy presented with pain in right lower limb and abdomen after a
      fall from a bullock cart. He was referred for management of pseudoaneurysm of the
      right common iliac artery. After CT angiogram, the vascular surgeon opined that
      child was not suitable for surgical patch or graft or endovascular stenting as
      there was no landing zone for the stent. Hence the child was treated with
      transcatheter closure with two Amplatzer duct occluder II (ADO II). On follow-up
      the symptoms and bruit disappeared. To the best of our knowledge this is the
      first case of pseudoaneurysm, treated with ADO II. 

PMID- 23852804
TI  - Enantioselective organocatalytic fluorination-induced Wagner-Meerwein
      rearrangement.

PMID- 23852805
TI  - On the "tertiary structure" of poly-carbenes; self-assembly of sp3-carbon-based
      polymers into liquid-crystalline aggregates.
AB  - The self-assembly of poly(ethylidene acetate) (st-PEA) into van der Waals
      stabilized liquid-crystalline (LC) aggregates is reported. The LC behavior of
      these materials is unexpected, and unusual for flexible sp(3)-carbon backbone
      polymers. Although the dense packing of polar ester functionalities along the
      carbon backbone of st-PEA could perhaps be expected to lead directly to rigid-rod
      behavior, molecular modeling reveals that individual st-PEA chains are actually
      highly flexible and should not reveal rigid-rod induced LC behavior. Nonetheless,
      st-PEA clearly reveals LC behavior, both in solution and in the melt over a broad
      elevated temperature range. A combined set of experimental measurements,
      supported by MM/MD studies, suggests that the observed LC behavior is due to self
      aggregation of st-PEA into higher-order aggregates. According to MM/MD modeling
      st-PEA single helices adopt a flexible helical structure with a preferred trans
      gauche syn-syn-anti-anti orientation. Unexpectedly, similar modeling experiments
      suggest that three of these helices can self-assemble into triple-helical
      aggregates. Higher-order assemblies were not observed in the MM/MD simulations,
      suggesting that the triple helix is the most stable aggregate configuration. DLS
      data confirmed the aggregation of st-PEA into higher-order structures, and
      suggest the formation of rod-like particles. The dimensions derived from these
      light-scattering experiments correspond with st-PEA triple-helix formation.
      Langmuir-Blodgett surface pressure-area isotherms also point to the formation of
      rod-like st-PEA aggregates with similar dimensions as st-PEA triple helixes. Upon
      increasing the st-PEA concentration, the viscosity of the polymer solution
      increases strongly, and at concentrations above 20 wt % st-PEA forms an
      organogel. STM on this gel reveals the formation of helical aggregates on the
      graphite surface-solution interface with shapes and dimensions matching st-PEA
      triple helices, in good agreement with the structures proposed by molecular
      modeling. X-ray diffraction, WAXS, SAXS and solid state NMR spectroscopy studies
      suggest that st-PEA triple helices are also present in the solid state, up to
      temperatures well above the melting point of st-PEA. Formation of higher-order
      aggregates explains the observed LC behavior of st-PEA, emphasizing the
      importance of the "tertiary structure" of synthetic polymers on their material
      properties.

PMID- 23852806
TI  - Immunocompatibility evaluation of hydrogel-coated polyimide implants for
      applications in regenerative medicine.
AB  - Immunocompatibility of gelatin-based hydrogels to be applied as implant coatings
      for local regenerative treatment has been studied. First, the bio- and immuno
      acceptability of the methacrylamide-modified gelatin hydrogels per se was
      screened. The results indicated that the hydrogels support cell growth. Metabolic
      activity of normal cells and permanent cell lines representing various cell types
      (endothelial, epithelial, fibroblast, and monocyte/macrophage) cultivated on the
      gelatin hydrogels was moderately lower compared to cells cultivated on tissue
      culture plastic. The cells cultivated on the hydrogels produced identical
      cytokines as the control cells although at lower levels. Importantly, no
      inflammatory activity, measured by nitric oxide and pro-inflammatory cytokine (IL
      1alpha, IL-6, and TNFalpha) production, was observed in peritoneal cells and
      monocyte/macrophage RAW 264.7 cell line cultivated on the hydrogels. Finally,
      polyimide (PI) implantable membranes were surface-modified with gelatin hydrogels
      and screened for their in vivo immunocompatibility. Their histological
      examination performed after subcutaneous implantation in mice produced a sound
      proof of immunoacceptability. Normal tissue repair, mild cellular infiltration
      and edema mainly induced by the surgery were observed after 2 and 6 days. No
      adverse tissue responses were induced by the implants. Analysis performed after 4
      and 9 weeks indicated areas of foreign body granuloma without formation of a
      fibrous capsule.

PMID- 23852809
TI  - A novel anti-VEGF targeting and MRI-visible smart drug delivery system for
      specific diagnosis and therapy of liver cancer.
AB  - A pH-responsive anticancer drug polymer conjugate p(aspartate)-graft-p(ethylene
      glycol)-dodecylamine-hydrazone-(adriamycin-levulinic acid) is synthesized as a
      magnetic resonance imaging (MRI)-visible and pH-sensitive drug delivery system.
      Being pH-sensitive, the anticancer drug ADR are stable in the polymeric micelles
      at neutral pH, resembling the physiological environment, whereas they release
      rapidly in acidic endosomal/lysosomal compartments of tumor cells for cancer
      therapy with the acid-linker breaking. For the purporse of MR imaging, the
      hydrophobic superparamagnetic iron oxide nanoparticles are encapsulated inside
      the core of the micelles. In order to identify the specific liver cancer tumors
      more efficiently, anti-vascular endothelial growth factor (anti-VEGF) is modified
      to the micelles. The stability studies show that all the conjugate@IO have
      excellent solubility and stability in stimulate biological media, suggesting that
      they have longer circulation time. Drug release studies in vitro show that the
      ADR release from the pH-sensitive polymeric micelles is significantly faster at
      pH 5.0 than at of pH 7.4. The tetrazolium dye method (MTT assay) shows that all
      the conjugate@IO exhibit low cytotoxicity and high antitumor activities against
      HepG2 cells. Furthermore, the anti-VEGF-conjugate@IO shows a high spin-spin (T2)
      relaxivity. In vivo MRI experiments on tumor-bearing mice demonstrate that the
      anti-VEGF-conjugate@IO achieves an appreciable accumulation into liver tumor,
      suggesting their potential utility as tumor-selective MRI contrast agents. 

PMID- 23852807
TI  - Which spinal lesions are associated with new bone formation in patients with
      ankylosing spondylitis treated with anti-TNF agents? A long-term observational
      study using MRI and conventional radiography.
AB  - OBJECTIVE: To study the relationship of spinal inflammation and fatty
      degeneration (FD) as detected by MRI and new bone formation seen on conventional
      radiographs (CRs) in ankylosing spondylitis (AS). METHODS: CRs at baseline, 2
      years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients
      treated with infliximab in European AS Infliximab Cohort were available. Relative
      risks (RR) were calculated with a general linear model after adjustment for
      within-patient variation. RESULTS: In a total of 1466 vertebral edges (VEs)
      without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the
      majority of which (57.4%) had no corresponding detectable MRI lesions at
      baseline. VEs with both inflammation and FD at baseline had the highest risk (RR
      3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that
      developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while
      inflammation at baseline with no FD at 2 years had the lowest risk for
      syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at
      baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only
      1 syndesmophyte developed within 5 years. CONCLUSIONS: Parallel occurrence of
      inflammation and FD at baseline and development of FD without prior inflammation
      after 2 years were significantly associated with syndesmophyte formation after 5
      years of anti-tumour necrosis factor (TNF) therapy. However, the sequence
      'inflammation-FD-new bone formation' was rarely observed, an argument against the
      TNF-brake hypothesis. Whether an early suppression of inflammation leads to a
      decrease of the risk for new bone formation remains to be demonstrated.

PMID- 23852810
TI  - Cytoplasmic HuR expression: correlation with cellular inhibitors of apoptosis
      protein-2 expression and clinicopathologic factors in oral squamous cell
      carcinoma cells.
AB  - BACKGROUND: HuR expression has been noted in several cancer types, in which it
      may contribute to increased expression of cellular inhibitors of apoptosis
      protein-2 (cIAP2) observed during tumorigenesis. METHODS: To assess the
      correlation between cIAP2 and HuR in cases of oral squamous cell carcinoma
      (OSCC), the expression patterns of HuR and cIAP2 were assessed by
      immunohistochemical analyses of 95 treated OSCC samples. RESULTS: In the tumor
      tissues, positive cytoplasmic HuR expression was evident in 71.6% of samples and
      positive cIAP2 expression was noted in 95.8% of samples. Positive cytoplasmic HuR
      expression was significantly associated with positive cIAP2 (p < .035) and high
      cIAP2 expression (p < .007), as well as high grade (p < .050). The inhibition of
      HuR expression by small interfering RNA or leptomycin B caused a reduction in the
      inducibility of cIAP2 in oral cancer cells. CONCLUSION: Cytoplasmic expression of
      HuR is associated with cIAP2 expression in OSCCs.

PMID- 23852808
TI  - Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient
      mismatch repair and epithelial-to-mesenchymal transition.
AB  - In most colorectal cancer (CRC) patients, outcome cannot be predicted because
      tumors with similar clinicopathological features can have differences in disease
      progression and treatment response. Therefore, a better understanding of the CRC
      biology is required to identify those patients who will benefit from chemotherapy
      and to find a more tailored therapy plan for other patients. Based on
      unsupervised classification of whole genome data from 188 stages I-IV CRC
      patients, a molecular classification was developed that consist of at least three
      major intrinsic subtypes (A-, B- and C-type). The subtypes were validated in 543
      stages II and III patients and were associated with prognosis and benefit from
      chemotherapy. The heterogeneity of the intrinsic subtypes is largely based on
      three biological hallmarks of the tumor: epithelial-to-mesenchymal transition,
      deficiency in mismatch repair genes that result in high mutation frequency
      associated with microsatellite instability and cellular proliferation. A-type
      tumors, observed in 22% of the patients, have the best prognosis, have frequent
      BRAF mutations and a deficient DNA mismatch repair system. C-type patients (16%)
      have the worst outcome, a mesenchymal gene expression phenotype and show no
      benefit from adjuvant chemotherapy treatment. Both A-type and B-type tumors have
      a more proliferative and epithelial phenotype and B-types benefit from adjuvant
      chemotherapy. B-type tumors (62%) show a low overall mutation frequency
      consistent with the absence of DNA mismatch repair deficiency. Classification
      based on molecular subtypes made it possible to expand and improve CRC
      classification beyond standard molecular and immunohistochemical assessment and
      might help in the future to guide treatment in CRC patients. 

PMID- 23852811
TI  - How growing up sweet can turn sour.

PMID- 23852812
TI  - Evidence of Ljungan virus specific antibodies in humans and rodents, Finland.
AB  - Ljungan virus (LV, genus Parechovirus, family Picornaviridae) is considered
      currently to be a rodent-borne virus. Despite suggested human disease
      associations, its zoonotic potential remains unclear. To date, LV antibody
      prevalence in both humans and rodents has not been studied. In this study, two
      different LV immunofluorescence assays (LV IFAs) were developed with LV genotypes
      1 (LV strain 87-012G) and 2 (LV strain 145SLG), and cross-neutralization and 
      reaction studies were carried out with LV strain 145SLG. Finally, a panel of 37
      Finnish sera was screened for anti-LV antibodies using two different LV IFAs (LV
      145SLG and LV 87-012G) and a neutralization (NT) assay (LV 145SLG), and 50
      samples from Myodes glareolus by LV IFA (LV 145SLG). The LV seroprevalence study
      showed 38% and 18% positivity in humans and M. glareolus, respectively. LV IFAs
      and NT assays were compared, and the results were in good agreement. The data are
      the first evidence of humans and rodents coming into contact with LV in Finland.
      Additional studies are required in order to acquire a better understanding of the
      prevalence, epidemiological patterns and possible disease association of LV
      infections.

PMID- 23852813
TI  - Determination and evaluation of the metals and metalloids in the Chapeu-de-couro
      (Echinodorus macrophyllus (Kunth) Micheli).
AB  - The Chapeu-de-couro (Echinodorus macrophyllus (Kunth) Micheli) is a native plant
      from Brazil, which has been mainly used in medicinal application being a potent
      antirheumatic and diuretic, in the production of soft drinks, and also in the
      ornamentation of aquariums. In this paper, the metals and metalloids for the
      leaves of chapeu-de-couro collected in the Paraguacu River from the city
      Cachoeira, Bahia State, Brazil, was determined and evaluated using multivariate
      analysis. The samples were digested using nitric acid and hydrogen peroxide and
      were analyzed using inductively coupled plasma mass spectrometry. The accuracy of
      the method was confirmed by analysis of a certified reference material of apple
      leaves, furnished by National Institute of Standard and Technology. The study
      involved 15 samples of the Paraguacu River. The results expressed as milligrams
      of element per kilogram of sample demonstrated that the concentration ranges
      varied: 1.39-5.27 for chromium, 44.85-165.39 for manganese, 0.55-0.84 for
      arsenic, 0.01-3.94 for antimony, and 0.18-0.31 for lead. The principal component
      analysis and hierarchical cluster analysis evidenced that the concentrations of
      the metals and metalloids varied according with the variations in the water of
      the Paraguacu. 

PMID- 23852814
TI  - Chemotherapy altered brain functional connectivity in women with breast cancer: a
      pilot study.
AB  - Adjuvant chemotherapy is associated with improvements in long-term cancer
      survival. However, reports of cognitive impairment following treatment emphasize
      the importance of understanding the long-term effects of chemotherapy on brain
      functioning. Cognitive deficits found in chemotherapy patients suggest a change
      in brain functioning that affects specific cognitive domains such as attentional
      processing and executive functioning. This study examined the processes
      potentially underlying these changes in cognition by examining brain functional
      connectivity pre- and post-chemotherapy in women with breast cancer. Functional
      connectivity examines the temporal correlation between spatially remote brain
      regions in an effort to understand how brain networks support specific cognitive
      functions. Nine women diagnosed with breast cancer completed a functional
      magnetic resonance imaging (fMRI) session before chemotherapy, 1 month after, and
      1 year after the completion of chemotherapy. Seed-based functional connectivity
      analyses were completed using seeds in the intraparietal sulcus (IPS) to examine
      connectivity in the dorsal anterior attention network and in the posterior
      cingulate cortex (PCC) to examine connectivity in the default mode network.
      Results showed decreased functional connectivity 1 month after chemotherapy that
      partially returned to baseline at 1 year in the dorsal attention network.
      Decreased connectivity was seen in the default mode network at 1 month and 1 year
      following chemotherapy. In addition, increased subjective memory complaints were
      noted at 1 month and 1 year post-chemotherapy. These findings suggest a
      detrimental effect of chemotherapy on brain functional connectivity that is
      potentially related to subjective cognitive assessment. 

PMID- 23852815
TI  - The effects of dissociated glucocorticoids RU24858 and RU24782 on TPA-induced
      skin tumor promotion biomarkers in SENCAR mice.
AB  - Glucocorticoids (GCs) are very effective at preventing carcinogen- and tumor
      promoter-induced skin inflammation, hyperplasia, and mouse skin tumor formation.
      The effects of GCs are mediated by a well-known transcription factor, the
      glucocorticoid receptor (GR). GR acts via two different mechanisms:
      transcriptional regulation that requires DNA-binding (transactivation) and DNA
      binding-independent protein-protein interactions between GR and other
      transcription factors, such as nuclear factor kappa B (NF-kappaB) or activator
      protein 1 (AP-1; transrepression). We hypothesize that the transrepression
      activities of the GR are sufficient to suppress skin tumor promotion. We obtained
      two GCs (RU24858 and RU24782) that have dissociated downstream effects and induce
      only transrepression activities of the GR in a number of systems. These compounds
      bind the GR with high affinity and repress AP-1 and NF-kappaB activities while
      showing a lack of GR transactivation. RU24858, RU24782, or control full GCs
      desoximetasone (DES) and fluocinolone acetonide (FA) were applied to the dorsal
      skin of SENCAR mice prior to application of the tumor promoter 12-O
      tetradecanoylphorbol-13-acetate (TPA), two times per week for 2 weeks. DES, FA
      and RU24858 reversed TPA-induced epidermal hyperplasia and proliferation, while
      RU24782 treatment had no effect on these markers of skin tumor promotion. All
      tested compounds decreased TPA-induced c-jun mRNA levels in skin. DES, FA, and
      RU24858, but not RU24782, were also able to reverse TPA-induced increases in the
      mRNA levels of COX-2 and iNOS. These findings show that RU24858 but not RU24782
      reduced TPA-induced epidermal hyperplasia, proliferation, and inflammation, while
      both compounds reversed c-jun mRNA increases in the skin.

PMID- 23852816
TI  - Scared witless about death--ovarian cancer narratives compared.
AB  - Fifty years ago, doctors did not tell their patients they had cancer. Improved
      patient-physician communication, feminization of the medical profession and
      increased patient empowerment may have improved matters. However, death is still
      a subject many doctors find difficult to deal with. We explore this issue in the
      context of medical humanities. In order to examine the different strategies in
      coping with illness and death, we compared illness perceptions in a literary
      text, W;t by Margaret Edson, about a woman who dies of ovarian cancer, with a
      personal narrative of a patient with ovarian cancer. Although there are many
      differences between the two patients in historical and cultural background,
      similarities were found in the way they cope with illness and death anxiety.
      Insight into illness perceptions and coping strategies of patients with cancer is
      important for raising awareness in clinicians, leading to improved understanding
      and better treatment of patients. 

PMID- 23852817
TI  - On the state of scientific English and how to improve it--part 3.

PMID- 23852821
TI  - N-tert-butyl triazolylidenes: catalysts for the enantioselective (3+2) annulation
      of alpha,beta-unsaturated acyl azoliums.

PMID- 23852822
TI  - Congenital fibrinogen disorders: an update.
AB  - Hereditary fibrinogen abnormalities comprise two classes of plasma fibrinogen
      defects: Type I, afibrinogenemia or hypofibrinogenemia, which has absent or low
      plasma fibrinogen antigen levels (quantitative fibrinogen deficiencies), and Type
      II, dysfibrinogenemia or hypodysfibrinogenemia, which shows normal or reduced
      antigen levels associated with disproportionately low functional activity
      (qualitative fibrinogen deficiencies). In afibrinogenemia and hypofibrinogenemia,
      most mutations of the FGA, FGB, or FGG fibrinogen encoding genes are null
      mutations. In some cases, missense or late truncating nonsense mutations allow
      synthesis of the corresponding fibrinogen chain but intracellular fibrinogen
      assembly and/or secretion are impaired. Afibrinogenemia is associated with mild
      to-severe bleeding, whereas hypofibrinogenemia is most often asymptomatic.
      Thromboembolism may occur either spontaneously or in association with fibrinogen
      substitution therapy. Women with afibrinogenemia suffer from recurrent pregnancy
      loss but this can also occur in women with hypofibrinogenemia. Dysfibrinogenemia,
      caused mainly by missense mutations, is commonly associated with bleeding,
      thrombophilia, or both; however, most individuals are asymptomatic.
      Hypodysfibrinogenemia is a subcategory of this disorder. Even in specialized
      laboratories, the precise diagnosis of some fibrinogen disorders may be
      difficult. Determination of the molecular defects is important because it gives
      the possibility to confirm the diagnosis, to elaborate a diagnostic strategy, to
      distinguish in some cases that the patient is at risk of thrombosis rather than
      bleeding, and to enable prenatal diagnosis. However, genotype-phenotype
      correlations are not easy to establish. Replacement therapy is effective in
      treating bleeding episodes, but because the pharmacokinetics of fibrinogen after
      replacement therapy is highly variable among patients, it is important to adjust
      the treatment individually. 

PMID- 23852823
TI  - Congenital prothrombin deficiency: an update.
AB  - Prothrombin (factor II [FII]) deficiency is a rare inherited coagulation
      disorder, having a prevalence of approximately 1 in 2,000,000. Two phenotypes can
      be distinguished: (1) true hypoprothrombinemia (type I deficiency), characterized
      by concomitantly low levels of the zymogen antigen; and (2) dysprothrombinemia
      (type II deficiency), characterized by the normal or near-normal synthesis of a
      dysfunctional protein. In the latter case, recent studies showed that particular
      mutations in the catalytic domain of active thrombin can even impair the enzyme
      interaction with antithrombin, favoring thromboembolic diseases. In some cases,
      hypoprothrombinemia associated with dysprothrombinemia was also described in
      compound heterozygous defects. Prothrombin is essential for the development of
      mammalian organisms. No living patient with undetectable plasma prothrombin has
      been reported to date. Prothrombin is encoded by a ~21 kb gene located on
      chromosome 11 and containing 14 exons. Thirty-nine different mutations have been
      identified and characterized in prothrombin deficiency. Many of these are present
      in the catalytic site, whereas some involve regulatory domains, such as the anion
      binding exosite I, the Na+-binding loop, and the light A-chain. Most
      hypoprothrombinemia-associated mutations are missense, but nonsense mutations
      leading to stop codons and one single nucleotide deletion have also been
      identified. Finally, recent developments in the therapy of congenital prothrombin
      deficiency are presented and discussed. 

PMID- 23852825
TI  - Non-lethal non-mosaic male with Conradi-Hunermann syndrome caused by a novel EBP
      c.356T>G mutation.

PMID- 23852824
TI  - Combined deficiency of coagulation factors V and VIII: an update.
AB  - Combined deficiency of factor V (FV) and FVIII (F5F8D) is an autosomal recessive
      bleeding disorder characterized by simultaneous decreases of both coagulation
      factors. This review summarizes recent reports on the clinical presentations,
      treatments, and molecular mechanism of F5F8D. Genetic studies identified LMAN1
      and MCFD2 as causative genes for this disorder, revealing a previously unknown
      intracellular transport pathway shared by the two important blood coagulation
      factors. LMAN1 and MCFD2 form a Ca2+-dependent cargo receptor complex that
      functions in the transport of FV/FVIII from the endoplasmic reticulum (ER) to the
      Golgi. Disrupting the LMAN1-MCFD2 receptor, complex formation is the primary
      molecular defect of missense mutations leading to F5F8D. The EF-hand domains of
      MCFD2 are necessary and sufficient for the interactions with both LMAN1 and
      FV/FVIII. Similarly, the carbohydrate recognition domain of LMAN1 contains
      distinct and separable binding sites for both MCFD2 and FV/FVIII. Therefore, FV
      and FVIII likely carry duel sorting signals that are separately recognized by
      LMAN1 and MCFD2 and necessary for the efficient ER-to-Golgi transport. FV and
      FVIII likely bind LMAN1 through the high-mannose N-linked glycans under the
      higher Ca2+ conditions in the ER and dissociate in the lower Ca2+ environment of
      the ER-Golgi intermediate compartment. 

PMID- 23852826
TI  - The associations between loss and posttraumatic stress and depressive symptoms
      followingHurricane Ike.
AB  - Disasters can have wide-ranging effects on individuals and their communities.
      Loss of specific resources (e.g., household contents, job) following a disaster
      has not been well studied, despite the implications for preparedness efforts and
      postdisaster interventions. OBJECTIVE: To provide information about the effects
      of loss on postdisaster distress, the present study assessed associations between
      disaster-related variables, including the loss of specific resources, and
      postdisaster distress. METHOD: Random-digit dialing methodology was used to
      recruit hurricane-affected adults from Galveston and Chambers, TX, counties one
      year after Hurricane Ike. Data from 1,249 survivors were analyzed to identify
      predictors of distress. RESULTS: Variables that were significantly associated
      with posttraumatic stress disorder symptoms included sustained losses, hurricane
      exposure, and sociodemographic characteristics; similar results were obtained for
      depressive symptoms. CONCLUSIONS: Together, these findings suggest risk factors
      that may be associated with the development of posthurricane distress that can
      inform preparedness efforts and posthurricane interventions.

PMID- 23852827
TI  - Cu-catalyzed formal methylative and hydrogenative carboxylation of alkynes with
      carbon dioxide: efficient synthesis of alpha,beta-unsaturated carboxylic acids.
AB  - The sequential hydroalumination or methylalumination of various alkynes catalyzed
      by different catalyst systems, such those based on Sc, Zr, and Ni complexes, and
      the subsequent carboxylation of the resulting alkenylaluminum species with CO2
      catalyzed by an N-heterocyclic carbene (NHC)-copper catalyst have been examined
      in detail. The regio- and stereoselectivity of the overall reaction relied
      largely on the hydroalumination or methylalumination reactions, which
      significantly depended on the catalyst and alkyne substrates. The subsequent Cu
      catalyzed carboxylation proceeded with retention of the stereoconfiguration of
      the alkenylaluminum species. All the reactions could be carried out in one-pot to
      afford efficiently a variety of alpha,beta-unsaturated carboxylic acids with well
      controlled configurations, which are difficult to construct by previously
      reported methods. This protocol could be practically useful and attractive
      because of its high regio- and stereoselectivity, simple one-pot reaction
      operation, and the use of CO2 as a starting material. 

PMID- 23852828
TI  - Residency schedule, burnout and patient care among first-year residents.
AB  - BACKGROUND: The 2011 US Accreditation Council for Graduate Medical Education
      (ACGME) mandates reaffirm the need to design residency schedules to augment
      patient safety and minimise resident fatigue. OBJECTIVES: To evaluate which
      elements of the residency schedule were associated with resident burnout and
      fatigue and whether resident burnout and fatigue were associated with lower
      perceived quality of patient care. METHODS: A cross-sectional survey of first
      year medicine residents at three hospitals in May-June 2011 assessed residency
      schedule characteristics, including hours worked, adherence to 2003 work-hour
      regulations, burnout and fatigue, trainee-reported quality of care and medical
      errors. RESULTS: Response rate was 55/76 (72%). Forty-two of the 55 respondents
      (76%) met criteria for burnout and 28/55 (51%) for fatigue. After adjustment for
      age, gender and residency programme, an overnight call was associated with higher
      burnout and fatigue scores. Adherence to the 80 h working week, number of days
      off and leaving on time were not associated with burnout or fatigue. Residents
      with high burnout scores were more likely to report making errors due to
      excessive workload and fewer reported that the quality of care provided was
      satisfactory. CONCLUSIONS: Burnout and fatigue were prevalent among residents in
      this study and associated with undesirable personal and perceived patient-care
      outcomes. Being on a rotation with at least 24 h of overnight call was associated
      with higher burnout and fatigue scores, but adherence to the 2003 ACGME work-hour
      requirements, including the 80 h working week, leaving on time at the end of
      shifts and number of days off in the previous month, was not. Residency schedule
      redesign should include efforts to reduce characteristics that are associated
      with burnout and fatigue.

PMID- 23852829
TI  - Community treatment orders do not reduce hospital readmission in people with
      psychosis.

PMID- 23852830
TI  - A false-positive on screening mammography has a negative psychosocial impact up
      to 3 years after receiving the all clear.

PMID- 23852831
TI  - Alterations in innate and adaptive immune leukocytes are involved in paediatric
      obesity.
AB  - BACKGROUND: Adipose tissue is the main source of the cytokines and adipokines
      that are increased in the context of obesity. The production of reactive oxygen
      species (ROS) and cytokines by circulating immune cells can be regulated by these
      pro-inflammatory factors even before infiltration into adipose tissue. OBJECTIVE:
      To investigate the alterations that can occur in circulating monocytes and
      lymphocytes in paediatric obesity. METHODS: In this study, 54 paediatric obese
      patients and 30 age-matched metabolically healthy individuals were enrolled.
      Intracellular cytokines were analyzed after phorbol myristate acetate (PMA) or
      leptin plus PMA stimulation of lymphocytes and monocytes by flow cytometry. ROS
      generation was measured using dichlorofluorescein-diacetate. Both a 'stimulation
      index' and a 'fold of increase' were calculated for statistical purposes.
      RESULTS: Both interferon gamma (IFN-gamma) production by circulating CD4+ and
      CD8+ lymphocytes and ROS production by monocytes following PMA stimulation were
      increased in obese patients. Leptin induced an increased production of IFN-gamma
      in both subsets of T cells and tumour necrosis factor alpha in monocytes, and
      linoleic acid induced a higher ROS production in monocytes. CONCLUSIONS: The
      distinct functional responses of circulating cells suggest that alterations in
      both innate and adaptive immune cells are involved in the maintenance of low
      grade inflammation in paediatric obesity.

PMID- 23852832
TI  - Topotactic phase transformation of the brownmillerite SrCoO2.5 to the perovskite
      SrCoO3- delta.
AB  - Pulsed laser epitaxy of brownmillerite SrCoO2.5 thin films and their phase
      transformation to the perovskite SrCoO3-delta are investigated. While the direct
      growth of the fully oxidized perovskite films is found to be an arduous task,
      filling some of oxygen vacancies into SrCoO2.5 by topotactic oxidation
      accompanies systematic evolution of electronic, magnetic, and thermoelectric
      properties, useful for many information and energy technologies. 

PMID- 23852834
TI  - Computational SNP analysis: current approaches and future prospects.
AB  - The computational approaches in determining disease-associated Non-synonymous
      single nucleotide polymorphisms (nsSNPs) have evolved very rapidly. Large number
      of deleterious and disease-associated nsSNP detection tools have been developed
      in last decade showing high prediction reliability. Despite of all these highly
      efficient tools, we still lack the accuracy level in determining the genotype
      phenotype association of predicted nsSNPs. Furthermore, there are enormous
      questions that are yet to be computationally compiled before we might talk about
      the prediction accuracy. Earlier we have incorporated molecular dynamics
      simulation approaches to foster the accuracy level of computational nsSNP
      analysis roadmap, which further helped us to determine the changes in the protein
      phenotype associated with the computationally predicted disease-associated
      mutation. Here we have discussed on the present scenario of computational nsSNP
      characterization technique and some of the questions that are crucial for the
      proper understanding of pathogenicity level for any disease associated mutations.

PMID- 23852835
TI  - Detection of human herpesvirus 7 DNA from the CSF in association with
      neurosarcoidosis.
AB  - This study reports a previously healthy, immunocompetent adult male in whom human
      herpesvirus 7 (HHV-7) DNA was detected continuously from the cerebrospinal fluid
      (CSF). This patient developed definite sarcoidosis with primary symptomatic
      manifestations in the central nervous system (CNS). The initial presentation was
      with loss of visual acuity and papilledema. Brain MR imaging at presentation
      confirmed papilledema, but otherwise there were no focal abnormalities or signs
      of hydrocephalus. CSF investigation revealed pleocytosis and elevated protein
      levels. HHV-7 DNA was detected repeatedly from CSF but not from blood over 1 year
      follow-up. High resolution computed tomography of lungs was normal. Positron
      emission tomography showed several metabolically active lymph nodes in the
      mediastinum, and the histopathological investigation revealed granulomatous
      inflammation consistent with sarcoidosis. The finding of HHV-7 DNA in the CSF in
      the context of neurosarcoidosis has not been reported previously. The detection
      of HHV-7 DNA may result from the selective activation of CD4+ T-lymphocytes in
      the CSF caused by neurosarcoidosis. Further studies are needed to establish
      whether the detection of HHV-7 DNA in the CSF in association with
      neurosarcoidosis represents a clinically significant HHV-7 CNS infection.

PMID- 23852836
TI  - Self-assemblies of pH-activatable PEGylated multiarm poly(lactic acid-co-glycolic
      acid)-doxorubicin prodrugs with improved long-term antitumor efficacies.
AB  - Two pH-activatable star-shaped prodrugs are synthesized through the condensation
      reaction between Y- or dumbbell-shaped poly(ethylene glycol)-poly(lactic acid-co
      glycolic acid) (PEG-PLGA) copolymer and acid-sensitive cis-aconityl-doxorubicin.
      The prodrugs self-assemble into micelles with favorable hydrodynamic radii and
      relatively low critical micelle concentrations. In vitro DOX release from prodrug
      micelles is accelerated by the decrease of the PLGA content or at the late
      endosomal pH. The efficient cellular uptake and intracellular DOX release of the
      prodrug micelles are confirmed and the improved long-term anti-proliferative
      activities of prodrug micelles are revealed. These features suggest that the
      prodrugs provide a favorable approach to construct effective polymeric drug
      delivery systems for malignancy therapy. 

PMID- 23852837
TI  - Predicting developmental disorder in infants using an artificial neural network.
AB  - Early recognition of developmental disorders is an important goal, and equally
      important is avoiding misdiagnosing a disorder in a healthy child without
      pathology. The aim of the present study was to develop an artificial neural
      network using perinatal information to predict developmental disorder at infancy.
      A total of 1,232 mother-child dyads were recruited from 6,150 in the original
      data of Karaj, Alborz Province, Iran. Thousands of variables are examined in this
      data including basic characteristics, medical history, and variables related to
      infants.  The validated Infant Neurological International Battery test was
      employed to assess the infant's development. The concordance indexes showed that
      true prediction of developmental disorder in the artificial neural network model,
      compared to the logistic regression model, was 83.1% vs. 79.5% and the area under
      ROC curves, calculated from testing data, were 0.79 and 0.68, respectively. In
      addition, specificity and sensitivity of the ANN model vs. LR model was
      calculated 93.2% vs. 92.7% and 39.1% vs. 21.7%. An artificial neural network
      performed significantly better than a logistic regression model. 

PMID- 23852838
TI  - Interleukin 17 receptor gene polymorphism in periimplantitis and chronic
      periodontitis.
AB  - Gene polymorphism of cytokines influencing their function has been known as a
      contributing factor in the pathogenesis of inflammatory diseases of the tooth and
      implant supporting tissues. The aim of this study was to investigate the
      association of IL-17R gene polymorphism (rs879576) with chronic periodontitis and
      periimplantitis in an Iranian population. 73 patients with chronic periodontitis,
      37 patients with periimplantitis and 83 periodontally healthy patients were
      enrolled in this study. 5cc blood was obtained from each subject's arm vein and
      transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's
      Salting Out technique. The DNA was transferred into 96 division plates,
      transported to Kbioscience Institute in United Kingdom and analyzed using the
      Kbioscience Competitive Allele Specific PCR (KASP) technique. Chi-square and
      Kruskal Wallis tests were used to analyze differences in the expression of
      genotypes and frequency of alleles in disease and control groups (P-Value less
      than 0.05 was considered statistically significant). There were no significant
      differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL
      17R gene (P=0.8239). Also comparison of frequency of alleles in SNP rs879576 of
      IL-17R gene between the chronic periodontitis group and periimplantitis group did
      not revealed statistically significant differences (P=0.8239). The enigma of IL
      17 and its polymorphism-role in periodontitis and periimplantitis is yet to be
      investigated more carefully throughout further research but this article
      demonstrates that polymorphism of IL-17R plays no significant role in incidence
      of chronic periodontitis and Periimplantitis. 

PMID- 23852839
TI  - The efficacy of clarithromycin in patients with severe nasal polyposis.
AB  - Although several treatments have been suggested for nasal polyposis, from medical
      to surgical, there is no standard guideline for the management of this disease.
      During recent years increasing attention has been directed toward the effects of
      macrolide antibiotics on chronic sinusitis and nasal polyposis. In this study, 
      the efficacy of clarithromycin on severe nasal polyposis were examined. In a
      Prospective, before - after study, forty patients with severe nasal polyposis
      received clarithromycin 500 mg twice a day for 8 weeks. At the beginning and end
      of treatment, the severity of patients' symptoms (using subjective analogue
      scale), computed tomography (CT) scan and endoscopic findings were recorded.
      After treatment, the severity of nasal obstruction, smelling problems, Post Nasal
      Discharge and rhinorrhea decreased significantly (P<0.05). Furthermore, the
      degree of sinus opacification in CT scan and endoscopic findings showed
      significant improvement. Most patients completed their treatment course without
      significant side effects. Although a course of clarithromycin improved nasal
      symptoms, polyp size and CT findings, further studies with more patients are
      required to recommend this drug as a general treatment in nasal polyposis. 

PMID- 23852840
TI  - Association between HDL particles size and myeloperoxidase/ paraoxonase-1
      (MPO/PON1) ratio in patients with acute coronary syndrome.
AB  - Myeloperoxidase (MPO) and paraoxonase-1 (PON1) are inflammatory and anti
      inflammatory enzymes, respectively that have been involved in the pathogenesis of
      coronary artery disease (CAD). In this study we sought to evaluate the relations
      of MPO and PON1 with high density lipoprotein (HDL) mean size in patients with
      acute coronary syndrome (ACS). Collectively, 50 control subjects and 50 patients
      with ACS were participated in this study. MPO level and PON1 activity was
      determined using immunoassay and colorimetric methods, respectively. HDL mean
      size was determined by a dynamic light scattering methodology. Other clinical
      risk factors were also determined by standard methods. The MPO/PON1 ratio amount
      was significantly higher in patients with ACS (1.49+/-1.10) than in control
      subjects (0.21+/-0.14) (P<0.01). There was a significant correlation between
      MPO/PON1 ratio and HDL mean size in patients with ACS. Amount of the enzymes and
      their relations to HDL particle size in patients with ACS may play a part in the
      pathogenesis of ACS. Also, MPO/PON1 ratio may be a robust predictor of ACS. 

PMID- 23852842
TI  - Factors affecting the efficacy of pramipexole in patients with restless legs
      syndrome.
AB  - Dopamine agonists, particularly nonergot dopamine agonists such as pramipexole,
      have become the mainstay of therapy for patients with symptoms of restless legs
      syndrome (RLS). This study was designed to evaluate the factors affecting the
      efficacy of pramipexole in patients with RLS. Fifty-nine eligible RLS patients
      referred to neurology clinic of Rasoul-e-Akram Hospital (Tehran, Iran) were
      recruited in this study. All of the patients received an oral dose of 0.18 mg
      pramipexole. The severity of RLS symptoms were evaluated including sleep
      disorder, symptomatic days per week and symptomatic hours per day, both at the
      beginning and at the end of follow-up time. Different baseline and follow-up
      variables were also recorded and their relationships with the outcomes were
      assessed. The mean severity values of different symptoms significantly decreased
      after treatment with pramipexole (P<0.001). Female gender (P<0.05) and duration
      of treatment (P<0.05) were significant factors to achieve >50% reduction in
      symptomatic days per week and symptomatic hours per day. Moreover, the cutoff
      point of 3.5 mo for duration of treatment could potentially differentiate >50%
      reduction in severity of sleep disorder from the ones with <50% reduction with
      sensitivity and specificity of 56.8% and 78.6%, respectively. Our findings show
      that female gender and duration of treatment were the factors affecting the
      effectiveness of pramipexole in RLS patients. If tolerated by the patients, a
      longer duration of treatment with pramipexole is more effective in RLS. 

PMID- 23852841
TI  - The role of cytomegalovirus, Haemophilus influenzae and Epstein Barr virus in
      Guillain Barre syndrome.
AB  - Guillain Barre Syndrome (GBS) is an inflammatory, usually demyelinating,
      polyneuropathy; clinically characterized by acute onset of symmetric progressive
      muscle weakness with loss of myotatic reflexes. Thirty five patients with GBS,
      defined clinically according to the criteria of Asbury and Cornblath, were
      recruited from three hospital affiliated to Tehran University of Medical
      Sciences. CONTROLS: As a control group 35 age and sex matched patients with other
      neurological diseases admitted to the same hospital at the same time, were
      included in our study. Serum samples were collected before treatment from each
      patient (within 4 weeks after the disease onset) and controls, and stored frozen
      at -80oC until serologic assays were done. Serologic testing of pretreatment
      serum was performed in all patients. Positive titer of virus specific IgM
      antibody against cytomegalovirus (CMV) was found in 6 cases and 2 controls. 34
      patients and 31 controls had high titer of anti Haemophilus influenzae IgG and
      one patient had serologic evidence of a recent Epstein Barr virus (EBV)
      infection. The mean titer of IgG antibody against Haemophilus influenzae in cases
      and controls was 5.21 and 2.97 respectively. Although serologic evidence of all
      these infections were more frequent in cases than in controls, only Haemophilus
      influenzae infection appeared to be significantly related to GBS (P=0.002).
      Eleven cases and 3 controls had high titers of IgG antibody against Haemophilus
      influenzae type B (titer >8). There is significant association between high titer
      of IgG antibody against Haemophilus influenzae and GBS (P=0.017). Our results
      provide further evidence that Haemophilus influenzae and probably CMV, can be
      associated with GBS.

PMID- 23852843
TI  - Quality of life in patients with bipolar I disorder: is it related to disorder
      outcome?
AB  - Bipolar I disorder (BID) and its treatments have shown to be associated with deep
      impacts on patients' subjective feelings and quality of life (QOL). There are
      also some comments about impact of these feelings on course and outcome of
      patients with BID. This study was aimed to evaluate quality of life in patients
      with BID and to assess its relationship with course of disorder. Fifty patients
      with BID were recruited based on the Structured Clinical Interview for DSM-IV
      Axis I Disorders (SCID-I) from May 2008 and followed for 12 months. Quality of
      life and mood disorder recurrence were assessed through World Health Organization
      Quality of Life and SCID-I tools respectively at baseline and after 6 and 12
      months. Repeated measures analysis and logistic regression were used to analyze
      the independent effect of QOL and demographic factors on BID recurrence. Fifty
      patients (66% male; 48% never married; 48% in primary school level) with mean +/-
      SE age and age of BID onset 33.8+/-1.5 and 26.6+/-1.1 years were studied. They
      had 3.4+/-0.6 episodes already. Twenty eight percent suffered from recurrences
      during the follow-up. The QOL scores at baseline, after 6 and 12 months were 70+/
      1.8, 69.6+/-1.1 and 73+/-1.3 respectively. There were no significant change in
      QOL and its sub-domains during the follow-up (P=0.37). QOL showed no independent
      relationship with BID recurrences (P>0.1). No change in the QOL during the follow
      up could denote lack of effectiveness of routine interventions on this factor.
      Also, short-term follow-up might be concerned as the possible reason. Of prime
      importance is to consider quality of life independently in treating patients with
      bipolar disorder.

PMID- 23852844
TI  - The validity of cardiopulmonary resuscitation skills in the emergency department
      using video-assisted surveillance: an Iranian experience.
AB  - The present study was designed to evaluate the quality of CPR procedures
      performed in Tehran's Rasool-e-Akram Hospital-- the first Emergency Medicine
      academic center in Iran-using a videotaped real-life (actual) CPR technique, with
      the aim of pointing out the defects and shortcomings in this regard. The
      performance of the CPR team in the emergency resuscitation room of Rasool-e-Akram
      Hospital was evaluated through videotaping. In an expert panel in the educational
      council of the emergency medicine group scored each item, which could be
      evaluated through videotaping, based on the existing guidelines. Fifty CPRs were
      videotaped between May to July 2008. From among the 33 CPRs which were recorded
      from the very first moment, 25 of them were started which the correct procedure,
      chest compression and ventilation, whereas procedures such as checking for pulse,
      getting an IV-line or intubation were performed as the first action in the
      remaining cases. While many believe CPR is performed properly in our center, the
      present study revealed that the performance is still distant from the desired
      ideal.

PMID- 23852845
TI  - A clinical microbiological study of corneal ulcer patients at western Gujarat,
      India.
AB  - Corneal ulcer is a major cause of blindness throughout the world. When the cornea
      is injured by foreign particles, there are chances of infection by the organism
      and development of ulcer. Bacterial infection in the cornea is invariably an
      alteration of the defense mechanism of the outer eye. It is essential to
      determine the local etiology within a given region when planning a corneal ulcer
      management strategy. Laboratory evaluation is necessary to establish the
      diagnosis and to guide the antibiotic therapy. One hundred corneal ulcer patients
      were studied by collecting their corneal scraping samples and processing at
      Clinical Microbiology department of Shree Meghaji Petharaj Shah Medical College,
      Jamnagar, Gujarat, India during a period of 17 months. All clinical microbiology
      laboratory procedures followed standard protocols described in the literature. 40
      (40%) patients from the age group of 20-70 years had been confirmed as - any
      organism culture positive - within the corneal ulcer patient population. Fungi
      were isolated from 26 (26%) corneal ulcer patients. The bacterial etiology was
      confirmed in 14 (14%) corneal ulcer patients. The major risk factors for mycotic
      keratitis were vegetative injury (16, (62%)), followed by conjunctivitis (4,
      (15%)), and blunt trauma (3, (11%)). Pseudomonas aeruginosa was the most commonly
      isolated bacterium (6, (43%)), followed by Proteus spp. (4, (29%)). Corneal
      Infections due to bacteria and filamentous fungi are a frequent cause of corneal
      damage. Microbiological investigation is an essential tool in the diagnosis of
      these infections. The frequency of fungal keratitis has risen over the past 20 to
      30 years. Prognosis of bacterial corneal infection has improved since the
      introduction of specific antibacterial therapy. 

PMID- 23852846
TI  - Incidence of hepatocellular carcinoma in patients with thalassemia who had
      hepatitis C.
AB  - Hepatitis is the infections of a common cause disease among poly transfused
      patients. Hepatitis C is slowed progression and inducing HCC. This study assessed
      HCC incidences, the role of iron and possible antitumor activity of chelators in
      170 thalassemia patients using deferoxamine (DFO) therapy. They are diagnosed
      with Hepatitis C due to positive PCR-RNA. They are Treated with IFN. The follow
      up program including tests every 3 Months and PCR-RNA, AFP and liver US every 6
      months. Whenever there was suspicion of liver malignancy, Biopsy was performed.
      From the total of 170 patients,  59.4% were male, and 40.6% were female. Mean age
      of thalassemia diagnosis was 2.69+/-5.403 (1-41) years and mean Age of hepatitis
      diagnosis was 17.37+/-7.263 (3-51) years. 92.4 % of Patient's MT, 0.6 % SS, 2.9%
      TI. the viral genome was 1a3a. 73.5% of patients had first course of therapy. The
      frequency of AFP greater than 10 was 5.9%. And the incidence of HCC was 0.6
      %(1/170) with a 95% confidence interval. The main risk factor for HCC was HCV
      infection in TM patients, but it was iron activity in TI patients. Iron chelation
      with DFO appeared to play a Protective role. 

PMID- 23852847
TI  - Pemphigoid gestationis: a retrospective study in southwest Iran.
AB  - Pemphigoid gestationis (PG) is a rare autoimmune bullous dermatosis of pregnancy
      usually presents in the second or third trimester. It is characterized by
      pruritic, urticarial plaques with the development of tense vesicles and bullae
      within the lesions. Pathogenesis of PG is not fully established, however, most
      patients develop circulating autoantibodies targeting the bullous pemphigoid (BP)
      180 antigen. The aim of this work is to draw a profile of the epidemiology,
      clinical aspects, treatment and evolution of the disease by studying hospital
      series. We retrospectively investigated the 13 patients who were diagnosed with
      PG based on hospital data at the Referral Center of Southwest Iran located in
      Ahvaz city between March 2002 and March 2011. The age of onset was 21 to 40 years
      (mean age: 27.5 years). The onset of the disease occurred in the second trimester
      of pregnancy in 6 patients and in the third trimester of pregnancy in 4 patients.
      One patient had a flare up of disease during the first trimester and two out of
      cases in puerperium period. In all cases, pruritus was the first symptom,
      followed by an erythematous vesiculobullous eruption.  The diagnosis of PG was
      confirmed by skin biopsy. Ten out of the patients treated with oral
      corticosteroids (0.5-1 mg/kg/day), one of the patients underwent oral
      corticosteroids plus topical glucocorticoid and the last patient treated with
      topical glucocorticoid. PG remains a rare dermatosis of pregnancy. Our series had
      two particularities compared to other studies: high frequency in primigravida and
      the frequent involvement of the face. Additionally our study demonstrated that
      improvement could occur faster and provide acceptable management if the treatment
      of the patients would be implemented sooner. 

PMID- 23852848
TI  - Quantum leadership: the implication for Iranian nursing leaders.
AB  - Quantum organizations are referred where stakeholders know how to access the
      infinite potential of the quantum field. Viewing healthcare organizations from
      perspective of quantum theory suggest new approaches into management techniques
      for effective and efficient delivery of healthcare services. This research is
      aimed to determine the quantum skills, quantum leadership characteristics and
      functions of Tehran University of Medical Sciences hospitals' nursing
      administrators. A cross-sectional, descriptive and analytical study was conducted
      among 25 nursing administrators of Tehran University of Medical Sciences (TUMS)
      hospitals, Tehran, Iran. The research tool for data collection was a self
      constructed questionnaire that measured the quantum skills, quantum leadership
      characteristics and functions of TUMS hospitals' nursing administrators. The
      validity of questionnaire was confirmed by 5 management science experts and its
      reliability was performed by using test-retest method yielded a Cronbach's alpha
      coefficient of 0.90. Data were collected and analyzed by SPSS software and t-test
      statistical methods. The results of this research showed that all respondents had
      desired quantum skills (75.71+/-5.98), quantum leadership characteristics
      (82.01+/-6.77), and quantum leadership functions (78.57+/-6.28) and total quantum
      leadership (78.76+/-4.50). Also, passing management training courses of the
      respondents was significantly correlated with their quantum leadership. Iranian
      healthcare organizations require quantum leadership that provides an important
      resource to advance Iranian nursing leadership to the organizational excellence.
      We hope Iranian hospitals' nursing leaders who have quantum skills potentially,
      present a highly developed sense of self and the ability to improve nursing care
      outcomes in these hospitals. 

PMID- 23852849
TI  - Knowledge of medical students of Tehran University of Medical Sciences regarding
      plagiarism.
AB  - The core concept of plagiarism is defined as the use of other people's ideas or
      words without proper acknowledgement. Herein, we used a questionnaire to assess
      the knowledge of students of Tehran University of Medical Sciences (TUMS)
      regarding plagiarism and copyright infringement. The questionnaire comprised 8
      questions. The first six questions of the questionnaire were translations of
      exercises of a book about academic writing and were concerning plagiarism in
      preparing articles. Questions number 7 and 8 (which were concerning plagiarism in
      preparing Microsoft PowerPoint slideshows and copyright infringement,
      respectively) were developed by the authors of the present study. The validity of
      the questionnaire was approved by five experts in the field of epidemiology and
      biostatistics. A pilot study consisting of a test and retest was carried to
      assess the reliability of the questionnaire. The sampling method was stratified
      random sampling, and the questionnaire was handed out to 74 interns of TUMS
      during July and August 2011. 14.9% of the students correctly answered the first
      six questions. 44.6% of the students were adequately familiar with proper
      referencing in Microsoft PowerPoint slideshows. 16.2% of the students understood
      what constitutes copyright infringement. The number of correctly answered
      questions by the students was directly proportionate to the number of their
      published articles. Knowledge of students of TUMS regarding plagiarism and
      copyright infringement is quite poor. Courses with specific focus on plagiarism
      and copyright infringement might help in this regard. 

PMID- 23852850
TI  - Idiopathic great saphenous phlebosclerosis.
AB  - Arterial sclerosis has been extensively described but reports on venous sclerosis
      are very sparse. Phlebosclerosis refers to the thickening and hardening of the
      venous wall. Despite its morphological similarities with arteriosclerosis and
      potential morbid consequences, phlebosclerosis has gained only little attention.
      We report a 72 year old male with paralysis and atrophy of the right leg due to
      childhood poliomyelitis who was referred for coronary artery bypass surgery. The
      great saphenous vein, harvested from the left leg, showed a hardened cord-like
      obliterated vein. Surprisingly, harvested veins from the atrophic limb were
      normal and successfully used for grafting. 

PMID- 23852851
TI  - Giant vulvar schwannoma: a case report.
AB  - Schwannoma is a solitary, slow growing,  benign tumour of the peripheral  nerve
      sheath, and it is most common locations are the head, neck, the flexor surfaces
      of the extremities, retroperitoneal and posterior mediastinium. External female
      genital organs are the least common location site of the schwannoma. Only a few
      cases of vulvar schwannoma have been reported.We report 65 year- old woman
      presented with a left vulvar swelling, which had been present for several years.
      The tumor size is 15x12 cm and slowly increased but it prevent patient activities
      such as walking and sitting. The tumor was resected for treatment and the
      histological examination confirmed to be a vulvar schwannoma. In our best
      knowledge, vulvar schwannoma in this case is the largest size in the literature. 

PMID- 23852852
TI  - Plasma corticosterone and leptin concentration in male and female rats: debatable
      facts.

PMID- 23852853
TI  - Pharmacogenetics of antidepressant drugs: an update after almost 20 years of
      research.
AB  - Major depressive disorder (MDD) is an emergent cause of personal and socio
      economic burden, both for the high prevalence of the disorder and the
      unsatisfying response rate of the available antidepressant treatments. No
      reliable predictor of treatment efficacy and tolerance in the single patient is
      available, thus drug choice is based on a trial and error principle with poor
      clinical efficiency. Among modulators of treatment outcome, genetic polymorphisms
      are thought to explain a significant share of the inter-individual variability.
      The present review collected the main pharmacogenetic findings primarily about
      antidepressant response and secondly about antidepressant induced side effects,
      and discussed the main strengths and limits of both candidate and genome-wide
      association studies and the most promising methodological opportunities and
      challenges of the field. Despite clinical applications of antidepressant
      pharmacogenetics are not available yet, previous findings suggest that genotyping
      may be applied in the clinical practice. In order to reach this objective,
      further rigorous pharmacogenetic studies (adequate sample size, study of better
      defined clinical subtypes of MDD, adequate covering of the genetic variability),
      their combination with the results obtained through complementary methodologies
      (e.g., pathway analysis, epigenetics, transcriptomics, and proteomics), and
      finally cost-effectiveness trials are required.

PMID- 23852854
TI  - A general mechanism for conditional expression of exaggerated sexually-selected
      traits.
AB  - Sexually-selected exaggerated traits tend to be unusually reliable signals of
      individual condition, as their expression tends to be more sensitive to
      nutritional history and physiological circumstance than that of other phenotypes.
      As such, these traits are the foundation for many models of sexual selection and
      animal communication, such as "handicap" and "good genes" models. Exactly how
      expression of these traits is linked to the bearer's condition has been a central
      yet unresolved question, in part because the underlying physiological mechanisms
      regulating their development have remained largely unknown. Recent discoveries
      across animals as diverse as deer, beetles, and flies now implicate the widely
      conserved insulin-like signaling pathway, as a common physiological mechanism
      regulating condition-sensitive structures with extreme growth. This raises the
      exciting possibility that one highly conserved pathway may underlie the evolution
      of trait exaggeration in a multitude of sexually-selected signal traits across
      the animal kingdom.

PMID- 23852855
TI  - Metal-free intramolecular carbocyanation of activated alkenes: functionalized
      nitriles bearing beta-quaternary carbon centers.

PMID- 23852856
TI  - Mindfulness, emotional dysregulation, impulsivity, and stress proneness among
      hypersexual patients.
AB  - OBJECTIVE: The current study explores relationships between mindfulness,
      emotional regulation, impulsivity, and stress proneness in a sample of
      participants recruited in a Diagnostic and Statistical Manual of Mental Disorder
      Fifth Edition Field Trial for Hypersexual Disorder and healthy controls to assess
      whether mindfulness attenuates symptoms of hypersexuality. METHOD: Hierarchal
      regression analysis was used to assess whether significant relationships between
      mindfulness and hypersexuality exist beyond associations commonly found with
      emotional dysregulation, impulsivity, and stress proneness in a sample of male
      hypersexual patients (n = 40) and control subjects (n = 30). RESULTS: Our results
      show a robust inverse relationship of mindfulness to hypersexuality over and
      above associations with emotional regulation, impulsivity, and stress proneness.
      CONCLUSIONS: These results suggest that mindfulness may be a meaningful component
      of successful therapy among patients seeking help for hypersexual behavior in
      attenuating hypersexuality, improving affect regulation, stress coping, and
      increasing tolerance for desires to act on maladaptive sexual urges and impulses.

PMID- 23852858
TI  - Advanced catalytic performance of Au-Pt double-walled nanotubes and their
      fabrication through galvanic replacement reaction.
AB  - Bimetallic tubular nanostructures have been the focus of intensive research as
      they have very interesting potential applications in various fields including
      catalysis and electronics. In this paper, we demonstrate a facile method for the
      fabrication of Au-Pt double-walled nanotubes (Au-Pt DWNTs). The DWNTs are
      fabricated through the galvanic displacement reaction between Ag nanowires and
      various metal ions, and the Au-Pt DWNT catalysts exhibit high active catalytic
      performances toward both methanol electro-oxidation and 4-nitrophenol (4-NP)
      reduction. First, they have a high electrochemically active surface area of 61.66
      m(2)  g(-1), which is close to the value of commercial Pt/C catalysts (64.76 m(2)
      g(-1)), and the peak current density of Au-Pt DWNTs in methanol oxidation is
      recorded as 138.25 mA mg(-1), whereas those of Pt nanotubes, Au/Pt nanotubes
      (simple mixture), and commercial Pt/C are 24.12, 40.95, and 120.65 mA mg(-1),
      respectively. The Au-Pt DWNTs show a markedly enhanced electrocatalytic activity
      for methanol oxidation compared with the other three catalysts. They also show an
      excellent catalytic performance in comparison with common Au nanotubes for 4
      nitrophenol (4-NP) reduction. The attractive performance exhibited by these
      prepared Au-Pt DWNTs can be attributed to their unique structures, which make
      them promising candidates as high-performance catalysts.

PMID- 23852859
TI  - Overexpression of CPE-DeltaN predicts poor prognosis in colorectal cancer
      patients.
AB  - Carboxypeptidase E (CPE) is one of the most important carboxypeptidases involved
      in biosynthesis of numerous peptide hormones and neurotransmitters and has an
      important role in endocrine regulation. A splice variant of CPE (CPE-DeltaN) has
      been detected and the mechanism of CPE-DeltaN action in tumorigenesis has been
      studied in many different cancers. The aim of this study was to examine CPE
      DeltaN expression in human colorectal cancer (CRC) and to evaluate its possible
      use as a potential prognostic marker. Two hundred nineteen primary colorectal
      tumors and corresponding normal tissues were included in the study. We have
      analyzed CPE-DeltaN isoform expression by qRT-PCR and Western blot in 219 CRC
      patients. Correlations between CPE-DeltaN mRNA expression and clinicopathological
      variables were determined with chi-square tests. Survival probabilities were
      determined using Kaplan-Meier analysis, and univariate and multivariate analyses
      of the prognostic factors were performed with a Cox regression model. Our results
      show that CPE-DeltaN is overexpressed in colorectal tumor tissue and that high
      CPE-DeltaN mRNA expression is closely correlated with tumor differentiation, pT
      classification, pN classification, tumor recurrence, and lymph node metastasis (P
      = 0.042, 0.036, 0.031, 0.006, and 0.008, respectively). However, no correlation
      was observed between CPE-DeltaN expression and age, gender, tumor localization,
      gross features, and the tumor size. In addition, patients with high CPE-DeltaN
      expression had a significantly shorter survival (P < 0.001, logrank test). Tumor
      differentiation, gross feature, pT classification, pN classification, tumor
      recurrence, lymph node metastasis, and CPE-DeltaN status were significantly
      associated with poor prognosis after performing a univariate Cox survival
      analysis. High CPE-DeltaN expression was also identified as an independent
      prognostic factor using a multivariate analysis (P = 0.011). Based on these
      results, we can conclude that CPE-DeltaN expression might be a potential
      prognostic marker for colorectal cancer patients.

PMID- 23852861
TI  - High level of CDK4 amplification is a poor prognostic factor in well
      differentiated and dedifferentiated liposarcoma.
AB  - The amplification of MDM2 and CDK4 is the main molecular feature of well
      differentiated liposarcomas (WDLS) and dedifferentiated liposarcomas (DDLS).
      Although the diagnostic usefulness of this molecular characteristic in
      liposarcomas has been investigated, its prognostic utility of quantitative gene
      level has not been explored. The aim of this study was to assess the prognostic
      significance of level of CDK4 amplification in MDM2-amplified WDLS/DDLS. MDM2
      amplification in liposarcomas was confirmed by fluorescence in situ
      hybridization. The copy number of MDM2 and CDK4 was further determined by
      quantitative PCR (qPCR) and multiplex ligation-dependent probe amplification.
      Among 56 MDM2-amplified liposarcomas, 30 cases were assigned as WDLS, and 26 as
      DDLS. When liposarcomas were classified by qPCR-determined CDK4 amplification
      levels, the high-CDK4 group showed significantly poorer progression free survival
      (P=0.001) and disease specific survival (P=0.033) than the low-CDK4 group.
      However, MDM2 amplification level did not show prognostic significance. In
      WDLS/DDLS, the level of CDK4 amplification was useful for prognosis prediction
      and precise stratification of patients for targeted therapy.

PMID- 23852860
TI  - NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and lung cancer risk:
      a meta-analysis.
AB  - No clear consensus has been reached on the NAD(P)H: quinone oxidoreductase 1
      (NQO1) gene C609T polymorphism and lung cancer risk. We performed a meta-analysis
      to summarize the possible association. We conducted a computer retrieval of
      PubMed and Embase databases prior to May 2013. References of retrieved articles
      were also screened. The fixed-effects model and the random-effects model were
      applied for dichotomous outcomes to combine the results of the individual
      studies. According to the inclusion criteria, 25 articles (32 studies) were
      finally included. There was no statistical association between C609T polymorphism
      and lung cancer risk in overall, East Asians, African Americans, or Hispanics. In
      Caucasians, a significant association was found in allele comparison model (T vs.
      C) (P = 0.04, OR = 1.09, 95% CI 1.00-1.19, P(heterogeneity) = 0.24, fixed-effects
      model). In the subgroup of squamous cell carcinoma, a borderline significance
      could be found in the dominant genetic model (TT + CT vs. CC) (P = 0.05, OR =
      1.20, 95% CI 1.00-1.43, P(heterogeneity) = 0.65, fixed-effects model).
      Significant association could also be found in allele comparison (T vs. C) (P =
      0.03, OR = 1.21, 95% CI 1.01-1.44, P(heterogeneity) = 0.68, fixed-effects model).
      In the subgroup of small cell lung cancer risk, significant association were
      found in allele comparison (T vs. C) (P = 0.03, OR = 1.68, 95%CI 1.05-2.68,
      P(heterogeneity) = 0.10, random-effects model) and in the homozygote comparison
      (TT vs. CC) (P = 0.02, OR = 2.79, 95% CI 1.14-6.85, P heterogeneity = 0.72, fixed
      effects model). No association was observed in adenocarcinoma subgroup. Our study
      suggested that NQO1 C609T polymorphism might associate with lung cancer risk in
      Caucasians. This polymorphism might also associate with squamous cell carcinoma
      and small cell lung cancer risk.

PMID- 23852862
TI  - The Synechocystis PCC6803 MerA-like enzyme operates in the reduction of both
      mercury and uranium under the control of the glutaredoxin 1 enzyme.
AB  - In a continuing effort to analyze the selectivity/redundancy of the three
      glutaredoxin (Grx) enzymes of the model cyanobacterium Synechocystis PCC6803, we
      have characterized an enzyme system that plays a crucial role in protection
      against two toxic metal pollutants, mercury and uranium. The present data show
      that Grx1 (Slr1562 in CyanoBase) selectively interacts with the presumptive
      mercuric reductase protein (Slr1849). This MerA enzyme plays a crucial role in
      cell defense against both mercuric and uranyl ions, in catalyzing their NADPH
      driven reduction. Like MerA, Grx1 operates in cell protection against both
      mercury and uranium. The Grx1-MerA interaction requires cysteine 86 (C86) of Grx1
      and C78 of MerA, which is critical for its reductase activity. MerA can be
      inhibited by glutathionylation and subsequently reactivated by Grx1, likely
      through deglutathionylation. The two Grx1 residues C31, which belongs to the
      redox active site (CX(2)C), and C86, which operates in MerA interactions, are
      both required for reactivation of MerA. These novel findings emphasize the role
      of glutaredoxins in tolerance to metal stress as well as the evolutionary
      conservation of the glutathionylation process, so far described mostly for
      eukaryotes.

PMID- 23852863
TI  - Structure of microcin B-like compounds produced by Pseudomonas syringae and
      species specificity of their antibacterial action.
AB  - Escherichia coli microcin B (Ec-McB) is a posttranslationally modified
      antibacterial peptide containing multiple oxazole and thiazole heterocycles and
      targeting the DNA gyrase. We have found operons homologous to the Ec-McB
      biosynthesis-immunity operon mcb in recently sequenced genomes of several
      pathovars of the plant pathogen Pseudomonas syringae, and we produced two
      variants of P. syringae microcin B (Ps-McB) in E. coli by heterologous
      expression. Like Ec-McB, both versions of Ps-McB target the DNA gyrase, but
      unlike Ec-McB, they are active against various species of the Pseudomonas genus,
      including human pathogen P. aeruginosa. Through analysis of Ec-McB/Ps-McB
      chimeras, we demonstrate that three centrally located unmodified amino acids of
      Ps-McB are sufficient to determine activity against Pseudomonas, likely by
      allowing specific recognition by a transport system that remains to be
      identified. The results open the way for construction of McB-based antibacterial
      molecules with extended spectra of biological activity. 

PMID- 23852857
TI  - Is dairy consumption associated with low cardiovascular disease risk in European
      adolescents? Results from the HELENA Study.
AB  - OBJECTIVE: To identify those food groups best discriminating individuals at
      high/low cardiovascular disease (CVD) risk and to investigate the relationship
      between dairy consumption and CVD risk factors (individual and scores) in
      adolescents (12.5-17.5 years) from eight European cities participating in the
      cross-sectional (2006-2007) HELENA (Healthy Lifestyle in Europe by Nutrition in
      Adolescence) project. METHODS: Diet, waist circumference, skin-folds thickness,
      systolic blood pressure, insulin resistance, triglycerides, total
      cholesterol/high-density lipoprotein ratio and cardiorespiratory fitness (CRF)
      were assessed in 511 (49.9% boys) adolescents. Individual z-scores of CVD risk
      factors were summed to compute sex-specific clustered CVD risk scores. RESULTS:
      Dairy emerged as the food group best discriminating adolescents at low/high CVD
      risk. In both genders, waist circumference and sum of skin-folds were inversely
      associated with consumption of milk and yogurt, and milk- and yogurt-based
      beverages, whereas a positive association was observed with CRF. Moreover, CVD
      risk score (beta = -0.230, P = 0.001) was also inversely associated with overall
      dairy consumption only in girls. DISCUSSION: Dairy consumption is associated with
      lower adiposity and higher CRF in these adolescents. An inverse association
      between CVD risk score and dairy consumption is also depicted in girls. The study
      adds further evidence to the scarce literature on the influence of milk and dairy
      products on adolescents' cardiovascular health.

PMID- 23852864
TI  - Benzoyl coenzyme a pathway-mediated metabolism of meta-hydroxy-aromatic acids in
      Rhodopseudomonas palustris.
AB  - Photoheterotrophic metabolism of two meta-hydroxy-aromatic acids, meta-, para
      dihydroxybenzoate (protocatechuate) and meta-hydroxybenzoate, was investigated in
      Rhodopseudomonas palustris. When protocatechuate was the sole organic carbon
      source, photoheterotrophic growth in R. palustris was slow relative to cells
      using compounds known to be metabolized by the benzoyl coenzyme A (benzoyl-CoA)
      pathway. R. palustris was unable to grow when meta-hydroxybenzoate was provided
      as a sole source of organic carbon under photoheterotrophic growth conditions.
      However, in cultures supplemented with known benzoyl-CoA pathway inducers (para
      hydroxybenzoate, benzoate, or cyclohexanoate), protocatechuate and meta
      hydroxybenzoate were taken up from the culture medium. Further, protocatechuate
      and meta-hydroxybenzoate were each removed from cultures containing both meta
      hydroxy-aromatic acids at equimolar concentrations in the absence of other
      organic compounds. Analysis of changes in culture optical density and in the
      concentration of soluble organic compounds indicated that the loss of these meta
      hydroxy-aromatic acids was accompanied by biomass production. Additional
      experiments with defined mutants demonstrated that enzymes known to participate
      in the dehydroxylation of para-hydroxybenzoyl-CoA (HbaBCD) and reductive
      dearomatization of benzoyl-CoA (BadDEFG) were required for metabolism of
      protocatechuate and meta-hydroxybenzoate. These findings indicate that, under
      photoheterotrophic growth conditions, R. palustris can degrade meta-hydroxy
      aromatic acids via the benzoyl-CoA pathway, apparently due to the promiscuity of
      the enzymes involved. 

PMID- 23852865
TI  - DNA uptake by the nosocomial pathogen Acinetobacter baumannii occurs during
      movement along wet surfaces.
AB  - The emergence of Acinetobacter baumannii as an increasingly multidrug-resistant
      nosocomial pathogen largely relies on acquisition of resistance genes via
      horizontal gene transfer. Here, we demonstrate that many clinical isolates of A.
      baumannii take up DNA while they move along wet surfaces. We show that both
      motility and DNA uptake are abolished after inactivation of pilT, which
      putatively encodes the type 4 pilus (T4P) retraction ATPase, and comEC, which
      putatively encodes the DNA uptake channel, respectively. Inactivation of pilT
      correlates with an increase in the number and length of pili with an average
      diameter of 7.2 nm. In the Galleria mellonella infection model, the comEC mutant
      is significantly attenuated, whereas the pilT mutant is not, dissecting
      biologically distinct roles of T4P and the DNA uptake channel. Collectively,
      these findings promote our understanding of the mechanisms of DNA uptake and
      resistance development in A. baumannii, which may also apply to other important
      pathogens. 

PMID- 23852866
TI  - Identification of a mycoloyl transferase selectively involved in O-acylation of
      polypeptides in Corynebacteriales.
AB  - We have previously described the posttranslational modification of pore-forming
      small proteins of Corynebacterium by mycolic acid, a very-long-chain alpha-alkyl
      and beta-hydroxy fatty acid. Using a combination of chemical analyses and mass
      spectrometry, we identified the mycoloyl transferase (Myt) that catalyzes the
      transfer of the fatty acid residue to yield O-acylated polypeptides. Inactivation
      of corynomycoloyl transferase C (cg0413 [Corynebacterium glutamicum mytC
      {CgmytC}]), one of the six Cgmyt genes of C. glutamicum, specifically abolished
      the O-modification of the pore-forming proteins PorA and PorH, which is critical
      for their biological activity. Expectedly, complementation of the cg0413 mutant
      with either the wild-type gene or its orthologues from Corynebacterium
      diphtheriae and Rhodococcus, but not Nocardia, fully restored the O-acylation of
      the porins. Consistently, the three-dimensional structure of CgMytC showed the
      presence of a unique loop that is absent from enzymes that transfer mycoloyl
      residues onto both trehalose and the cell wall arabinogalactan. These data
      suggest the implication of this structure in the enzyme specificity for protein
      instead of carbohydrate. 

PMID- 23852867
TI  - Synthetic effect between envelope stress and lack of outer membrane vesicle
      production in Escherichia coli.
AB  - Outer membrane vesicles (OMVs) are composed of outer membrane and periplasmic
      components and are ubiquitously secreted by Gram-negative bacteria. OMVs can
      disseminate virulence factors for pathogenic bacteria as well as serve as an
      envelope stress response. From a transposon mutant screen for OMV phenotypes, it
      was discovered that an nlpA mutant of Escherichia coli produces fewer OMVs than
      the wild type, whereas a degP mutant produces higher levels of OMVs. NlpA is an
      inner-membrane-anchored lipoprotein that has a minor role in methionine import.
      DegP is a periplasmic chaperone/protease for misfolded envelope proteins that is
      critical when cells are heat shocked. To reveal how these proteins contribute to
      OMV production, the mutations were combined and the double mutant analyzed. The
      DeltanlpA DeltadegP strain displayed a high-temperature growth defect that
      corresponded to the production of fewer OMVs than produced by the DeltadegP
      strain. This phenotype also pertained to other undervesiculation mutations in a
      DeltadegP background. The hypovesiculation phenotype of DeltanlpA in the wild
      type strain as well as in the degP deletion strain was found to be a stationary
      phase phenomenon. The periplasm of the DeltanlpA DeltadegP strain was determined
      to contain significantly more protein in stationary phase than the wild type.
      Additionally, misfolded DegP substrate outer membrane porins were detected in
      DeltadegP mutant-derived OMVs. These data suggest that an accumulation of
      envelope proteins resulting from decreased vesiculation was toxic and contributed
      to the growth defect. We conclude that OMV production contributes to relieve the
      envelope of accumulated toxic proteins and that NlpA plays an important role in
      the production of vesicles in stationary phase. 

PMID- 23852868
TI  - Initiation with elongator tRNAs.
AB  - In all domains of life, initiator tRNA functions exclusively at the first step of
      protein synthesis while elongator tRNAs extend the polypeptide chain. Unique
      features of initiator tRNA enable it to preferentially bind the ribosomal P site
      and initiate translation. Recently, we showed that the abundance of initiator
      tRNA also contributes to its specialized role. This motivates the question, can a
      cell also use elongator tRNA to initiate translation under certain conditions? To
      address this, we introduced non-AUG initiation codons CCC (Pro), GAG (Glu), GGU
      (Gly), UCU (Ser), UGU (Cys), ACG (Thr), AAU (Asn), and AGA (Arg) into the uracil
      DNA glycosylase gene (ung) used as a reporter gene. Enzyme assays from log-phase
      cells revealed initiation from non-AUG codons when intracellular initiator tRNA
      levels were reduced. The activity increased significantly in stationary phase.
      Further increases in initiation from non-AUG codons occurred in both growth
      phases upon introduction of plasmid-borne genes of cognate elongator tRNAs. Since
      purine-rich Shine-Dalgarno sequences occur frequently on mRNAs (in places other
      than the canonical AUG codon initiation contexts), initiation with elongator
      tRNAs from the alternate contexts may generate proteome diversity under stress
      without compromising genomic integrity. Thus, by changing the relative amounts of
      initiator and elongator tRNAs within the cell, we have blurred the distinction
      between the two classes of tRNAs thought to be frozen through years of evolution.

PMID- 23852869
TI  - Functional interactions of VirB11 traffic ATPases with VirB4 and VirD4 molecular
      motors in type IV secretion systems.
AB  - Pilus biogenesis and substrate transport by type IV secretion systems require
      energy, which is provided by three molecular motors localized at the base of the
      secretion channel. One of these motors, VirB11, belongs to the superfamily of
      traffic ATPases, which includes members of the type II secretion system and the
      type IV pilus and archaeal flagellar assembly apparatus. Here, we report the
      functional interactions between TrwD, the VirB11 homolog of the conjugative
      plasmid R388, and TrwK and TrwB, the motors involved in pilus biogenesis and DNA
      transport, respectively. Although these interactions remained standing upon
      replacement of the traffic ATPase by a homolog from a phylogenetically related
      conjugative system, namely, TraG of plasmid pKM101, this homolog could not
      replace the TrwD function for DNA transfer. This result suggests that VirB11
      works as a switch between pilus biogenesis and DNA transport and reinforces a
      mechanistic model in which VirB11 proteins act as traffic ATPases by regulating
      both events in type IV secretion systems. 

PMID- 23852870
TI  - Acetylation of the response regulator RcsB controls transcription from a small
      RNA promoter.
AB  - Nepsilon-lysine acetylation was recently discovered on many bacterial proteins
      that function in diverse cellular processes. Thus, many questions remain
      unanswered. For example, what mechanisms regulate lysine acetylation? Does
      acetylation affect physiology? To help answer these questions, we studied the
      Escherichia coli response regulator and transcription factor RcsB, which is
      reported to be acetylated in vitro. To characterize RcsB acetylation, we
      monitored transcription from the rprA promoter, which requires RcsB. The
      conventional view is that RcsB is activated by phosphorylation through either the
      Rcs phosphorelay or acetyl phosphate. We affirmed that rprA transcription
      requires phosphorylated RcsB and showed that acetyl-phosphate (AcP) is a
      phosphoryl group donor to RcsB. However, a mutant that accumulates AcP (ackA)
      exhibited a reduction in rprA transcription instead of the predicted increase.
      rprA transcription also diminished in the cobB mutant, which lacks the only known
      E. coli protein deacetylase. This suggests the existence of an inhibitory
      mechanism that involves lysine acetylation, a supposition supported by the
      observation that RcsB isolated from the ackA or cobB mutant was hyperacetylated.
      Finally, we used a genetic approach to identify an AckA- and CobB-sensitive
      lysine (Lys-154) that controls RcsB activity. We propose that acetylation
      inhibits RcsB activity and that some of this inhibition acts through the
      acetylation of Lys-154. 

PMID- 23852871
TI  - Characterization of a novel RNA polymerase mutant that alters DksA activity.
AB  - The auxiliary factor DksA is a global transcription regulator and, with the help
      of ppGpp, controls the nutritional stress response in Escherichia coli. Although
      the consequences of its modulation of RNA polymerase (RNAP) are becoming better
      explained, it is still not fully understood how the two proteins interact. We
      employed a series of genetic suppressor selections to find residues in RNAP that
      alter its sensitivity to DksA. Our approach allowed us to identify and
      genetically characterize in vivo three single amino acid substitutions: beta'
      E677G, beta V146F, and beta G534D. We demonstrate that the mutation beta' E677G
      affects the activity of both DksA and its homolog, TraR, but does not affect the
      action of other secondary interactors, such as GreA or GreB. Our mutants provide
      insight into how different auxiliary transcription factors interact with RNAP and
      contribute to our understanding of how different stages of transcription are
      regulated through the secondary channel of RNAP in vivo. 

PMID- 23852872
TI  - Mutations in hemG mediate resistance to salicylidene acylhydrazides,
      demonstrating a novel link between protoporphyrinogen oxidase (HemG) and
      Chlamydia trachomatis infectivity.
AB  - Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of
      Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth
      and development of Chlamydia species. However, since the inhibition of Chlamydia
      growth by SAH is suppressed by the addition of excess iron and since SAHs have an
      iron-chelating capacity, their role as specific T3S inhibitors is unclear. We
      investigated here whether SAHs exhibit a function on C. trachomatis that goes
      beyond iron chelation. We found that the iron-saturated SAH INP0341 (IS-INP0341)
      specifically affects C. trachomatis infectivity with reduced generation of
      infectious elementary body (EB) progeny. Selection and isolation of spontaneous
      SAH-resistant mutant strains revealed that mutations in hemG suppressed the
      reduced infectivity caused by IS-INP0341 treatment. Structural modeling of C.
      trachomatis HemG predicts that the acquired mutations are located in the active
      site of the enzyme, suggesting that IS-INP0341 inhibits this domain of HemG and
      that protoporphyrinogen oxidase (HemG) and heme metabolism are important for C.
      trachomatis infectivity. 

PMID- 23852873
TI  - Evidence for a key role of cytochrome bo3 oxidase in respiratory energy
      metabolism of Gluconobacter oxydans.
AB  - The obligatory aerobic acetic acid bacterium Gluconobacter oxydans oxidizes a
      variety of substrates in the periplasm by membrane-bound dehydrogenases, which
      transfer the reducing equivalents to ubiquinone. Two quinol oxidases, cytochrome
      bo3 and cytochrome bd, then catalyze transfer of the electrons from ubiquinol to
      molecular oxygen. In this study, mutants lacking either of these terminal
      oxidases were characterized. Deletion of the cydAB genes for cytochrome bd had no
      obvious influence on growth, whereas the lack of the cyoBACD genes for cytochrome
      bo3 severely reduced the growth rate and the cell yield. Using a respiration
      activity monitoring system and adjusting different levels of oxygen availability,
      hints of a low-oxygen affinity of cytochrome bd oxidase were obtained, which were
      supported by measurements of oxygen consumption in a respirometer. The H(+)/O
      ratio of the DeltacyoBACD mutant with mannitol as the substrate was 0.56 +/- 0.11
      and more than 50% lower than that of the reference strain (1.26 +/- 0.06) and the
      DeltacydAB mutant (1.31 +/- 0.16), indicating that cytochrome bo3 oxidase is the
      main component for proton extrusion via the respiratory chain. Plasmid-based
      overexpression of cyoBACD led to increased growth rates and growth yields, both
      in the wild type and the DeltacyoBACD mutant, suggesting that cytochrome bo3
      might be a rate-limiting factor of the respiratory chain. 

PMID- 23852875
TI  - Rotavirus activity and meteorological variations in an Asian subtropical city,
      Hong Kong, 1995-2009.
AB  - Rotavirus is a leading cause of severe infectious diarrhea in infants and young
      children aged <5 years. Rotavirus infections have minimal to strong seasonality
      depending on geographical locations. In this study, a comprehensive retrospective
      analysis was performed to evaluate the association between rotavirus admission
      and multiple key meteorological variables, including air temperature, relative
      humidity, atmospheric pressure, and solar radiation over a 15-year period from
      1995 to 2009 in Hong Kong. Rotavirus infections were found to show a distinct
      cyclical pattern with an annual peak in cold season. The weekly number of cases
      showed the strongest correlation with average air temperature of the previous 7
      days (rho=-0.69; P<0.0001), followed by atmospheric pressure (rho=+0.67;
      P<0.0001); whereas only weak correlation with relative humidity (rho=-0.252;
      P<0.0001) and solar radiation (rho=-0.312; P<0.0001) was observed. Curve fitting
      regression analysis suggested that the correlation was nonlinear in nature in
      which the effect was more profound towards lower air temperature and higher
      atmospheric pressure conditions. In binary logistic regression analysis, a final
      model that included air temperature (<= 20 degrees C) and atmospheric pressure
      (>= 1,013 hPa) predicted correctly 85.3% and 82.6% of weeks with rotavirus
      activity above and below the baseline level, respectively. In multivariate
      Poisson model, air temperature and solar radiation were independent factors
      associated with the weekly number of rotavirus cases, adjusted for seasonal
      variation. In summary, the current study provides evidence suggesting that local
      seasonal activity of rotavirus correlated strongly with air temperature, followed
      by atmospheric pressure but only minimally with relative humidity in pre-vaccine
      era.

PMID- 23852874
TI  - Identification of a new class of adenosine deaminase from Helicobacter pylori
      with homologs among diverse taxa.
AB  - Early studies of Helicobacter pylori's nutritional requirements alluded to a
      complete purine salvage network in this organism. Recently, this hypothesis was
      confirmed in two strains of H. pylori, whose purine requirements were satisfied
      by any single purine base or nucleoside. Most of the purine conversion enzymes in
      H. pylori have been studied using mutant analysis; however, the gene encoding
      adenosine deaminase (ADD) in H. pylori remained unidentified. Through stepwise
      protein purification followed by matrix-assisted laser desorption ionization-time
      of flight mass spectrometry (MALDI-TOF), we discovered that H. pylori ADD is
      encoded by hp0267, an apparently essential gene. Hp0267 shares no sequence
      homology with previously characterized ADDs, yet both are members of the
      amidohydrolase superfamily. Hp0267 is grouped within cog0402, while other ADDs
      studied to date are found in cog1816. The hp0267 locus was previously
      misannotated as encoding a chlorohydrolase. Using purified recombinant Hp0267, we
      determined the enzyme's pH optimum, temperature optimum, substrate specificity,
      and estimated kinetic constants. In contrast to other known ADDs, Hp0267 contains
      Fe(II) as the relevant metal ligand. Furthermore, Hp0267 exhibits very low
      deaminase activity on 2'-deoxyadenosine, a substrate that is readily hydrolyzed
      by cog1816 ADDs. Our preliminary comparative genomic analysis suggests that
      Hp0267 represents a second enzyme class of adenosine deaminase whose phyletic
      distribution among prokaryotes is broad. 

PMID- 23852876
TI  - Biocompatibility and preclinical feasibility tests of a temperature-sensitive
      hydrogel for the purpose of surgical wound pain control and cartilage repair.
AB  - We recently introduced a novel pluronic F127 and hyaluronic acid-based hydrogel
      (HG) designed to deliver a broad range of therapeutics. The reverse-thermal
      responsive HG exhibits physical properties that seem to be ideal for the local
      delivery of drug- and cell-based therapies to specific anatomic sites through
      percutaneous injection. However, questions related to the HG's safety and
      efficacy must first be addressed. To address these issues, we performed standard
      in vitro cytotoxicity and drug release tests and in vivo biocompatibility tests
      in a rat model. In addition, we determined whether the HG was an effective stem
      cell carrier in a rat cartilage defect model. We found that the HG showed
      viability and biocompatibility levels similar to those reported for F127 or
      hyaluronic acid alone. In vitro drug release studies with bupivacaine, a drug
      used clinically for local pain relief, revealed that after an initial burst
      bupivacaine was released continuously for 10 days. Stem cells loaded in the HG
      were retained in situ and stimulated cartilage regeneration in experimental
      defects. Taken as a whole, these findings support further efforts to develop the
      HG as a versatile system for the delivery of a wide range of therapeutic agents
      in humans. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 2013.

PMID- 23852877
TI  - Catalytic, enantioselective, and highly chemoselective bromocyclization of
      olefinic dicarbonyl compounds.

PMID- 23852878
TI  - Enhancing electron mobility at the LaAlO3 /SrTiO3 interface by surface control.
AB  - Mobility of electrons confined at the LaAlO3 /SrTiO3 interface is significantly
      enhanced by surface control using surface charges and adsorbates, reaching a low
      temperature value more than 20 000 cm(2) V(-1) s(-1) . A uniform trend that
      mobility increases with decreasing sheet carrier density is observed.

PMID- 23852879
TI  - Personality pathology factors predict recurrent major depressive disorder in
      emerging adults.
AB  - OBJECTIVE: Prior investigations consistently indicate that personality pathology
      is a risk factor for recurrence of major depressive disorder (MDD). Lack of
      emipircal support, however, for the Diagnostic and Statistical Manual of Mental
      Disorders (DSM) Fourth Edition organization of Axis II disorders supports the
      investigation of empirically derived factors of personality pathology as
      predictors of recurrence. METHOD: A sample of 130 previously depressed emerging
      adults (80% female; aged 18 to 21 years) were assessed for personality disorder
      symptoms at baseline. Participants were then followed for 18 months to identify
      MDD recurrence during the first 2 years of college. RESULTS: Based on a previous
      factor analysis of DSM personality disorder criteria, eight personality pathology
      factors were examined as predictors of MDD recurrence. Survival analysis
      indicated that factors of interpersonal hypersensitivity, antisocial conduct, and
      social anxiety were associated with increased risk of MDD recurrence.
      CONCLUSIONS: These findings suggest that an empirically based approach to
      personality pathology organization may yield useful predictors of MDD recurrence
      during emerging adulthood.

PMID- 23852880
TI  - Fire as a soil-forming factor.
AB  - In the span of a human generation, fire can, in theory, impact all the land
      covered by vegetation. Its occurrence has many important direct and indirect
      effects on soil, some of which are long-lasting or even permanent. As a
      consequence, fire must be considered a soil-forming factor, on par with the
      others traditionally recognized, namely: parent material, topography, time,
      climate, living beings not endowed with the power of reason, and humans. 

PMID- 23852881
TI  - Power discourses of fish death: case of linnunsuo peat production.
AB  - This article explores the peat production impacts on Jukajoki river in Finland by
      implementing discourse analysis. Four discourses are explored: state truth
      statements; company statements that are in close proximity of state power;
      discourses provided by the local community Selkie, who provided counter
      narratives to the official views; and finally media and related discourses. In
      conclusion, the discourses by the state and closely related actors (A-B)
      comprised implementation of their power and justifying it at the expense of those
      who are excluded from such power, in this case the village. The village narrative
      (C) contains elements that strongly contradict the statements provided by those
      with power. The results indicate local communities should be taken more
      seriously. The systematic denial of local peoples' rights should be reviewed, and
      local participation in environmental permit assessments implemented. 

PMID- 23852882
TI  - The wisdom of neurologists.

PMID- 23852883
TI  - False accusations in an investigative context: differences between suggestible
      and non-suggestible witnesses.
AB  - False sexual abuse allegations have spurred research on suggestibility, on the
      assumption that leading questions may produce false accusations. Most
      researchers, however, have not measured the likelihood that those who respond to
      suggestive questioning will take the next step and make a formal (false)
      accusation. The present study incorporates both aspects of abuse investigations:
      suggestibility (i.e., responsiveness to questions in a leading interview) and
      false accusations (i.e., signing a formal complaint against an innocent suspect).
      Participants (N = 129) were observed in a laboratory session and then interviewed
      twice about their experiences by an interviewer who suggested that the laboratory
      assistant had behaved inappropriately. Although only 17% of the participants were
      suggestible, 39% agreed to sign the complaint. Suggestible participants were
      significantly more likely to make a false accusation than were non-suggestible
      participants. However, because of the low rate of suggestibility, most false
      accusations were made by non-suggestible participants. Implications for the legal
      system are discussed.

PMID- 23852884
TI  - Nanoscale topography and chemistry affect embryonic stem cell self-renewal and
      early differentiation.
AB  - Adherent cells respond to a wide range of substrate cues, including chemistry,
      topography, hydrophobicity, and surface energy. The cell-substrate interface is
      therefore an important design parameter in regenerative medicine and tissue
      engineering applications, where substrate cues are used to influence cell
      behavior. Thin films comprising 4.5 nm (average diameter) gold nanoparticles
      coated with a mixture of two alkanethiols can confer hemispherical topography and
      specific chemistry to bulk substrates. The behavior of murine embryonic stem
      cells (ESCs) on the thin films can then be compared with their behavior on self
      assembled monolayers of the same alkanethiols on vapor-deposited gold, which lack
      the topographical features. Cells cultured both with and without differentiation
      inhibitors are characterized by immunofluorescence for Oct4 and qPCR for Fgf5,
      Foxa2, Nanog, Pou5f1, and Sox2. Nanoscale chemistry and topography are found to
      influence stem cell differentiation, particularly the early differentiation
      markers, Fgf5 and Foxa2. Nanoscale topography also affects Oct4 localization,
      whereas the chemical composition of the substrate does not have an effect. It is
      demonstrated for the first time that ESCs can sense topographical features
      established by 4.5 nm particles, and these findings suggest that nanoscale
      chemistry and topography can act synergistically to influence stem cell
      differentiation. This study furthers the understanding of the effects of these
      substrate properties, improving our ability to design materials to control stem
      cell fate. 

PMID- 23852885
TI  - Incorporation of growth factor loaded microspheres into polymeric electrospun
      nanofibers for tissue engineering applications.
AB  - Nanofibrous double-layer matrices were prepared by electrospinning technique with
      the bottom layer formed from PCL (poly-epsilon-caprolactone)/PLLA (poly-l-lactic
      acid) nanofibers and the upper layer from PCL/Gelatin nanofibers. Bottom layer
      was designed to give mechanical strength to the system, whereas upper layer
      containing gelatin was optimized to improve the cell adhesion. Gelatin
      microspheres were incorporated in the middle of two layers for controlled growth
      factor delivery. Successful fabrication of the blend nanofibers were shown by
      spectroscopy. Scanning electron microscopy results demonstrated that bead-free
      nanofibers with uniform morphology could be obtained by 10% w/v concentrations of
      PCL/PLLA and PCL/Gelatin solutions. Microspheres prepared by 15% gelatin
      concentration and cross-linked with 7.5% glutaraldehyde solution were chosen
      after in vitro release studies for the incorporation to the double-layer
      matrices. The optimized conditions were used to prepare fibroblast growth factor
      2 (FGF-2) loaded microspheres. Preliminary cell culture studies showed that the
      FGF-2 could be actively loaded into the microspheres and enhanced the cell
      attachment and proliferation. The complete system had a slow degradation rate in
      saline (18% weight loss in 2 months) and it could meanwhile preserve its
      integrity. This sandwich system prevented microsphere leakage from the scaffold,
      and the hydrophilic and bioactive nature of the fibers at the upper layer
      promoted cell attachment to the surface. PLLA/PCL layer, on the other hand,
      improved the mechanical properties of the system and enabled better handling.

PMID- 23852886
TI  - Self-assembly versus stepwise synthesis: heterometal-organic frameworks based on
      metalloligands with tunable luminescence properties.
AB  - A new family of heterometal-organic frameworks has been prepared by two synthesis
      strategies, in which IFMC-26 and IFMC-27 are constructed by self-assembly and
      IFMC-28 is obtained by stepwise synthesis based on the metalloligand
      (IFMC=Institute of Functional Material Chemistry). IFMC-26 is a (3,6)-connected
      net and IFMC-27 is a (4,8)-connected 3D framework. The metalloligands {Ni(H4
      L)}(NO3 )2 are connected by binuclear lanthanide clusters giving rise to a 2D
      sheet structure in IFMC-28. Notably, IFMC-26-Eux Tby and IFMC-28-Eux Tby have
      been obtained by changing the molar ratios of raw materials. Owing to the
      porosity of IFMC-26, Tb(3+) @IFMC-26-Eu and Eu(3+) @IFMC-26-Tb are obtained by
      postencapsulating Tb(III) and Eu(III) ions into the pores, respectively. Tunable
      luminescence in metal-organic frameworks is achieved by the two kinds of doping
      methods. In particular, the quantum yields of heterometal-organic frameworks are
      apparently enhanced by postencapsulation of Ln(III) ions. 

PMID- 23852887
TI  - Screening of phage-displayed human liver cDNA library against doxorubicin with
      drug-immobilized monolithic polyacrylamide cryogel.
AB  - Monolithic polyacrylamide cryogel was prepared and utilized as a new matrix for
      drug immobilization to screen against phage-displayed human liver cDNA library.
      The macropores and hydrophilic nature of the cryogel made it possible for phage
      particles to pass unhindered. Doxorubicin, an anticancer drug, was covalently
      bonded to the monolithic cryogel by the glutaraldehyde method, and after five
      rounds of affinity selection performed in an SPE cartridge, phage clones that
      displayed Homo sapiens methyl CpG binding protein 2 (MeCP2 ) were selectively
      enriched. The interaction between doxorubicin and MeCP2 displayed phages was
      further validated by studying the retention of doxorubicin on MeCP2 phage-coupled
      cryogel. These results demonstrate that drug-coupled polyacrylamide cryogel might
      be a promising kind of matrix for screening target proteins against phage
      displayed library.

PMID- 23852888
TI  - Detection of Merkel cell polyomavirus in oral samples of renal transplant
      recipients without Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine cancer, with
      approximately 80% of cases associated with Merkel cell polyomavirus (MCPyV). The
      lack of information concerning its occurrence in non-MCC immunosuppressed
      populations led to the investigation of MCPyV DNA in saliva and oral biopsies
      from 60 kidney allograft recipients and 75 non-transplanted individuals (control
      group). In contrast to herpesviruses, which was also investigated (CMV, HHV-6A,
      and B, HHV-7) MCPyV was detected predominantly in patients with oral lesions
      (gingivitis and/or periodontitis) of both transplanted and non-transplanted
      groups (P=0.016) and in the saliva of the transplanted group (P=0.009). MCPyV co
      detection with CMV (P=0.048), and HHV-6 (P=0.020) in the saliva of transplanted
      patients requires further investigation on a possible role of co-infection.

PMID- 23852889
TI  - Small study finds that 3 years after prostate cancer treatment, men may report
      high quality of life and functioning.

PMID- 23852890
TI  - Data citation and the author byline: who's line is it anyway?

PMID- 23852891
TI  - Knockdown of PLA2G2A sensitizes gastric cancer cells to 5-FU in vitro.
AB  - BACKGROUND-AIM: Elevated expression of the PLA2G2A phospholipase in gastric
      cancer (GC) is associated with improved patient survival. PLA2G2A is also an
      important regulator of proliferation, invasion and metastasis in GC. However, no
      relation about PLA2G2A and chemosensitivity in GC cells was reported. 5
      Fluorouracil (5-FU) is widely used for treatment of advanced gastric cancer.
      However, it is common for such patients to develop resistance to 5-FU, and this
      drug resistance becomes a critical problem for chemotherapy. The mechanisms
      underlying this resistance are largely unknown. In the present study, we
      investigated whether PLA2G2A could confer 5-FU resistance or sensitise in GC
      cells in vitro. MATERIALS AND METHODS: The 5-FU sensitivity of GC cell lines SGC
      7901, MKN-45, RF-48, N87, AGS, MKN-28, RF-1, MGC-803 were determined by MTT
      assays. PLA2G2A levels were determined by western blot assays. The effects of 5
      FU on PLA2G2A expression were determined in vitro. PLA2G2A was inhibited by
      silencing of the PLA2G2A using small interfering RNA in vitro. PLA2G2A was
      overexpressed by transfection of full-long PLA2G2A cDNA in vitro, and the effects
      were evaluated on 5-FU sensitivity. RESULTS: The cell lines SGC-7901, MKN-45, RF
      48 and N87 were sensitive, whereas AGS, MKN-28, RF-1 and MGC-803 were resistant
      to 5-FU. Significant correlation was observed between basal PLA2G2A and 5-FU
      sensitivity. Silencing of PLA2G2A increased 5-FU killing in 5-FU-treated cells,
      and overexpression of PLA2G2A decreased 5-FU killing in 5-FU-treated cells.
      CONCLUSIONS: PLA2G2A was correlated with sensitivity to 5-FU. Silencing of
      PLA2G2A was sensitive to 5-FU treatment. Thus, PLA2G2A may be a useful
      therapeutic target for a subset of gastric cancers.

PMID- 23852892
TI  - Downregulation of CD24 inhibits invasive growth, facilitates apoptosis and
      enhances chemosensitivity in gastric cancer AGS cells.
AB  - BACKGROUND AND AIM: The human CD24 antigen is a small heavily glycosylated cell
      surface protein, which is expressed in a large variety of solid tumors,including
      gastric cancer. Enriched on the surface of many tumor cells,CD24 promotes tumor
      growth,invasion and metastasis and confers resistance to some chemotherapeutic
      drugs.In this study, we investigated the possible effect of CD24 suppression on
      proliferation, apoptosis, migration, invasion and chemosensitivity of gastric
      cancer (GC) cells. MATERIALS AND METHODS: We down-regulated CD24 expression by
      RNA interference and investigated the effects on proliferation, apoptosis,
      chemosensitivity to doxorubicin, malignant and metastatic potential of a human
      gastric cancer cell line, AGS, CD24-suppressed clones, AGS-CD24-siRNA-C2, AGS
      CD24-siRNA-C4 and AGS-CD24-siRNA-C5 in vitro. We evaluated the effects of CD24
      suppression in vivo on xenograft tumor growth and metastatic properties following
      tail iv AGS-CD24-siRNA-C2, AGS-CD24-siRNA-C4 and AGS-CD24-siRNA-C5 clones. We
      also investigated the effect of CD24-siRNA followed by doxorubicin administration
      treatment on the xenograft tumor growth. RESULTS: CD24 suppressed showed
      significantly decreased proliferation, invasion and increased apoptosis as well
      as increased chemosensitivity to doxorubicin in vitro and in vivo. CONCLUSIONS:
      CD24 involves in proliferation, invasion and chemosensitivity of human gastric
      cancer cell line AGS, and that down-regulation of CD24 protein expression
      decreases the metastatic potential and increases chemosensitivity of gastric
      cancer (GC) cells. Thus, CD24 may be a promising therapeutic target for gastric
      cancer.

PMID- 23852893
TI  - Computational identification of specific splicing regulatory elements from RNA
      seq in lung cancer.
AB  - BACKGROUND: Lung cancer is the most common cause of cancer-related death
      worldwide. Recently, deep transcriptional sequencing has been used as an
      effective genomic assay to get an insight into this disease. AIM: This study is
      carried out to identify specific regulatory elements (SREs) in lung cancer.
      MATERIALS AND METHODS: The RNA-sequencing data on lung cancer sample and normal
      sample were downloaded from NCBI. TopHat and Cufflinks were used to analyze
      differential alternative splicing in lung cancer by using RNA-sequencing data.
      Further, we searched specific SREs in lung cancer through finding over
      represented hexamers around high expression exons. RESULTS: According to the
      Jensen-Shannon divergence between two samples and the p-value of t-test, we found
      53 genes with differential alternative splicing in lung cancer. In the analysis
      of SREs, we found 763 specific SREs between lung cancer sample and normal sample.
      CONCLUSIONS: These results may give an insight into how alternative splicing
      causes differential expression in lung cancer.

PMID- 23852894
TI  - Propofol inhibits invasion and enhances paclitaxel- induced apoptosis in ovarian
      cancer cells through the suppression of the transcription factor slug.
AB  - BACKGROUND AND AIM: Propofol is one of the most commonly used intravenous
      anaesthetic agents during cancer resection surgery. It has recently found that
      propofol has the effect to inhibit cancer cell migration and invasion and
      sensitize cancer cells to chemotherapy. However, the role of the propofol on the
      ovarian cancer cells is unknown. In the present study, we explored the effect of
      propofol on invasion and chemosensitization of ovarian cancer cells to
      paclitaxel. MATERIALS AND METHODS: The paclitaxel sensitivity of ovarian cancer
      cell lines HO-8910PM, H0-8910, SKOV-3, OVCAR-3, COC1 and ES-2 were determined by
      MTT assays. The Slug levels in the cell lines and the effects of propofol on Slug
      levels in the cell lines were determined by western blot assays. The effect of
      propofol on invasion, migration and paclitaxel-induced ovarian cancer apoptosis
      was determined by Boyden chamber assays, cell MTT, TUNEL assays. RESULTS: The
      results showed that the cell lines COC1, H0-8910 and ES-2 were sensitive, whereas
      HO-8910PM, OVCAR-3, SKOV-3, were resistant to paclitaxel. Significant correlation
      was observed between basal Slug levels and paclitaxel sensitivity. Paclitaxel
      treatment increased Slug levels. Treatment with propofol induced apoptosis and
      increased paclitaxel killing of all paclitaxel-sensitive and -resistant ovarian
      cancer cells followed by significant decrease in the Slug levels. Treatment with
      propofol inhibits invasion and migration. CONCLUSIONS: These data suggest a new
      mechanism by which the propofol inhibits invasion and metastasis,enhances
      paclitaxel-induced ovarian cancer cell apoptosis through suppression of Slug.

PMID- 23852895
TI  - Update on post-traumatic stress syndrome after anesthesia.
AB  - BACKGROUND: Between 0.5% and 2% of surgical patients undergoing general
      anesthesia may experience awareness with explicit recall. These patients are at a
      risk for developing anxiety symptoms which may be transient or can lead to post
      traumatic stress disorder (PTSD). AIM: The aim of this review was to assess the
      prevalence of PTSD after intraoperative awareness episodes and analyze patients'
      complaints, type and timing of assessment used. METHODS: PubMed, MEDLINE and The
      Cochrane Library were searched up until October 2012. Prospective and
      retrospective studies on human adult subjects describing prevalence of PTSD
      and/or psychological sequalae after awareness episodes were included. RESULTS:
      Seven studies were identified. Prevalence of PTSD ranged from 0 to 71%. Acute
      emotions such as fear, panic, inability to communicate and feeling of
      helplessness were the only patients' complaints that were significantly
      correlated to psychological sequelae including PTDS. There were cases that
      reported psychological symptoms after 2-6 hours from awakening (%) or 30 days
      after (%). Previous studies used psychological scales lacking of dissociation
      assessment. CONCLUSIONS: Whenever an awareness episode is suspected, a
      psychological assessment with at least three interviews at 2-6 h, 2-36 h and 30
      days must be performed in order to collect symptoms associated with both early
      and delayed retrieval of traumatic event. As a dissociative state could hide the
      expression of reactive symptoms after intraoperative awareness, future studies
      should be focused on detecting dissociative symptoms in order to carry out a
      prompt and appropriate treatment aimed at avoiding long-term psychological
      disability.

PMID- 23852896
TI  - Effects of isoflurane in an intoxication model: experimental study.
AB  - BACKGROUND: Isoflurane is a volatile anaesthetic that has been commonly used
      since 1980. The major metabolites of isoflurane are fluoride ion and
      trifluoroacetate, both excreted in the urine. AIM: This study manage to show the
      histopathological findings of ingested isoflurane on liver, kidney and lugs in an
      animal model. Twenty-one rabbits were selected and divided into three groups:
      Group Isoflurane-5 (I-5); Group Isoflurane-10 (I-10); and Group Control (C). Each
      group consisted of seven rabbits. I-5 and I-10 received 5 ml/kg and 10 ml/kg of
      liquid isoflurane, respectively, via nasogastric tube, while C received 5 ml/kg
      saline (0.9% NaCI). All animals in I-5 and I-10 were sacrificed without
      anesthetic drug administration. Tissue samples from livers, kidneys and lungs
      were collected, preserving tissue unity and avoiding infliction of any trauma.
      Samples were fixed in 10% formalin solution, embedded in paraffin blocks and
      sliced into 5 MUm sections. To investigate the effects of isoflurane, sections
      were examined under light microscope and histopathological changes were scored.
      RESULTS: Mean injury scores and the appearance of portal lymphocyte infiltration
      in liver samples showed significant increases in I-5 and I-10 compared to C (p =
      0.005, p = 0.001 and p = 0.001, respectively). Mean lung injury scores revealed
      significant increases after isoflurane treatment in I-5 and I-10 compared to C (p
      = 0.026 and p = 0.017, respectively). CONCLUSIONS: Ingested isoflurane led to
      mild liver and lung injuries in rabbits.

PMID- 23852897
TI  - Prevalence of plasmid-mediated qnr determinants and gyrase alteration in
      Klebsiella pneumoniae isolated from a university teaching hospital in Malaysia.
AB  - BACKGROUND AND OBJECTIVES: The ciprofloxacin resistance of Klebsiella (K.)
      pneumoniae is mediated primarily through alterations in type II topoisomerase
      (gyrA) gene and plasmid-mediated quinolone resistance-conferring genes (qnr).
      This study aimed to define the prevalence of plasmid-mediated quinolone
      resistance-conferring genes (qnr) and type II topoisomerase (gyrA) alterations of
      a population of ciprofloxacin-resistant (n = 21), intermediate (n = 8), and
      sensitive (n = 18) K. pneumoniae isolates obtained from a teaching hospital at
      Kuala Lumpur, Malaysia. MATERIALS AND METHODS: A multiplex PCR assay was
      performed for simultaneous detection of qnrA, qnrB and qnrS. Sequence analysis of
      the amplified gyrA and gyrB regions of the isolates were performed. RESULTS: The
      findings in this study revealed the emergence of a high prevalence (48.9%) of qnr
      determinants in our isolates. Four variants of plasmid-mediated qnr determinants
      (qnrB1, qnrB6, qnrB10 and qnrS1) were detected from 11 (52.4%) ciprofloxacin
      resistant, 5 (62.5%) intermediate and 7 (38.9%) sensitive isolates. gyrA
      alterations were detected from 18 (85.7%) ciprofloxacin-resistant isolates.
      Single gyrA alterations, Ser83->Tyr, Ser83->Ile, and Asp87->Gly, and double
      alterations, Ser83->Phe plus Asp87->Ala and Ser83->Tyr plus Asp87->Asn were
      detected. While ciprofloxacin resistance was significantly associated with gyrA
      alteration (Ser83, p = 0.003; Asp87, p = 0.005; double alteration, p = 0.016), no
      significant association of ciprofloxacin resistance was noted with the presence
      of qnr determinants (p = 0.283). CONCLUSIONS: The findings in this study
      demonstrate the emergence of qnr determinants and gyrA alterations contributed to
      the development and spread of fluoroquinolone resistance in the Malaysian
      isolates.

PMID- 23852898
TI  - Naloxone blocks the beneficial effects of aqueous extract of Murraya koenigii
      (L.) Spreng leaves in models of pain.
AB  - AIM: This study investigated the antinociceptive effects of aqueous extract of
      Murraya koenigii (AEMK) leaves (200, 400 and 800 mg/kg, orally) on animal models
      of acute and persistent pain and its modulation by naloxone. MATERIALS AND
      METHODS: Antinociceptive effects were assessed using tail-flick, hot plate and
      formalin tests in mice. To differentiate between central and peripheral
      antinociceptive effect of AEMK, naloxone (2 mg/kg) was administered along with
      the 800 mg/kg dose of extract. Morphine was used as a standard drug. RESULTS:
      AEMK and morphine significantly increased the tail-flick latency (tfl) and paw
      licking/jumping latency in tail-flick and hot plate tests, respectively, in
      comparison to control. Also, in both the tests AEMK and morphine significantly
      increased the AUC0-120 min. In formalin test, AEMK (400 mg/kg and 800 mg/kg) and
      morphine significantly reduced licking time in both early and late phases in
      comparison to control. CONCLUSIONS: Thus, in all three pain models AEMK showed
      antinociceptive effect, which was blocked by naloxone suggesting the involvement
      of opioidergic central mechanism.

PMID- 23852899
TI  - Safety of intra-articular hip injection of hyaluronic acid products by ultrasound
      guidance: an open study from ANTIAGE register.
AB  - OBJECTIVE: We developed a standardized technique for ultrasound guided intra
      articular injection of the hip joint with the purpose of extending routine intra
      articular injection of hyaluronans and steroids to the hip, as commonly used in
      the knee. In this article we report the safety of this technique in an extended
      series of patients. PATIENTS AND METHODS: Patients were injected supine with an
      anterosuperior approach under ultrasound guidance. The Us probe is applied with a
      target device for biopsy. RESULTS: The standardised technique was used to inject
      1906 patients with 4002 injections of hyaluronan products over a four-year
      period. The treatment was well tolerated with few, and exclusively local, side
      effects. CONCLUSIONS: The administration of hyaluronans under ultrasound-guided
      intra-articular injection is a safe technique for treatment of rheumatic diseases
      of the hip.

PMID- 23852900
TI  - In vitro effect of Sambucus ebulus on scolices of Hydatid cysts.
AB  - OBJECTIVES: Echinococcosis infection is caused in humans by the larval stage of
      cestodes belonging to the genus Echinococcus. Hydatid cyst cured by percutaneous
      aspiration, infusion of scolicidal agents with reaspiration or surgery. Many
      scolicidal agents have been used for inactivation of the cyst's content, but most
      of them are not safe due to their unanticipated side effects. In the present
      study, the scolicidal effect of methanolic extract of Sambucus (S.) ebulus fruit
      is investigated. MATERIALS AND METHODS: Protoscolices were aseptically aspirated
      from sheep livers having hydatid cysts. Four concentrations (1, 10, 50 and 100 mg
      ml-1) of S. ebulus extract were used for 5, 10, 30 and 60 min. Viability of
      protoscolices was confirmed by 0.1% Eosin staining. RESULTS: The results of our
      study indicated that methanolic extract of S. ebulus fruit showed a high
      scolicidal activity in vitro (p < 0.0001). CONCLUSIONS: Methanolic extract of S.
      ebulus showed high scolicidal activity in vitro. It might be used as a scolicidal
      cause in the surgical treatment of the hydatid cyst. However, further research on
      the in vivo efficacy of S. ebulus extract and its potential side effects is
      recommended.

PMID- 23852901
TI  - Unusual localization of a primary hydatid cyst: a subcutaneous mass in the
      paraumbilical region.
AB  - Hydatid cyst disease caused by Echinoccus granulosus is not a rare disease and
      mostly localized in liver and lung. The localization of the disease in the
      subcutaneous paraumbilical region without any other organ involvement is a unique
      existence that we present. A 63-year-old Turkish male complaining of abdominal
      distention and pain had an abdominal mass for one year. When the patient came to
      our Clinic, we detected a 4x5 cm mass in the left quadrant- paraumbilical region
      by using ultrasonography. Complete surgical resection of the mass was performed
      with uneventful post-operative recovery. Histopathological examination of the
      surgical specimen demonstrated a multive-sicular hydatid cyst. When a
      subcutaneous cystic mass is detected in a patient, regarding the region where he
      lives and endemicity, hydatid cyst should be considered.

PMID- 23852902
TI  - Clinical significance of serum hepcidin-25 levels in predicting invasive fungal
      disease in patients after transplantation.
AB  - BACKGROUND: Currently, it is important to identify a good biomarker to predict
      treatment-related complications in patients with transplantation. This study
      aimed to evaluate the significance of serum hepcidin-25 in predicting invasive
      fungal disease (IFD) after transplantation. PATIENTS AND METHODS: A total of 57
      patients who underwent transplantation were included in this study, and their
      serum samples were obtained and stored at -80 degrees C for analysis. The serum
      hepcidin-25 were assayed using enzyme-liked immunosorbent assay (ELISA), and
      hypersensitive C reactive protein (hsCRP) and 1,3-beta-D glucan were measured
      using standard laboratory techniques. These indices were monitored weekly, from
      one week before transplantation to four weeks after transplantation. RESULTS: The
      median pretransplant serum hepcidin-25 level was 37.00 ng/mL which was higher
      than that of healthy volunteers (p < 0.001). Because the higher hepcidin-25 level
      of the third tertile among the patients was 39.855 ng/mL, we set a cutoff level
      of 40 ng/mL to divide them into low- and high-hepcidin-25 groups (n = 38 and 19,
      respectively). The prevalences of the documented infection in the two groups were
      2.6% and 26%, respectively (p = 0.019). The high-hepcidin-25 group was monitored
      after transplantation. The hepcidin-25 level peaked one week after
      transplantation, followed by gradual decrease. The plasma (1-3)-beta-D-glucan
      reached the summit two week. The proven of IFD was delayed 10 days on average
      after hepcidin-25 had arrived summit and 5 days after (1-3)-beta-D-glucan peaked.
      CONCLUSIONS:  The pretransplant serum hepcidin-25 level would be a useful
      indicator for predicting the risk of infection after transplantation; and the
      dynamic changes of hepcidin-25 in patients with high-hepcidin-25 group would help
      to predict IFD after transplantation.

PMID- 23852903
TI  - The relationship of the mean platelet volume and C-reactive protein levels with
      mortality in ischemic stroke patients.
AB  - BACKGROUND AND OBJECTIVES: The relationship of the mean platelet volume (MPV) and
      C-reactive protein (CRP) values with mortality in patients with ischemic stroke
      is not clear. Besides, the correlation between CRP and MPV in patients with
      ischemic stroke has not been adequately studied yet. In the present study, our
      aim is to investigate the interrelationship of the CRP and MPV parameters
      together with their influence on mortality in patients with acute ischemic
      stroke. PATIENTS AND METHODS: Sixty-three patients with acute ischemic stroke
      have been enrolled in the study. The stroke patients were divided into 2 groups
      as those who died within the first 10 days and those who survived. The MPV and
      CRP in both groups have been compared. Also, the MPV obtained from the ischemic
      stroke patients were compared with the MPV of the healthy volunteers. RESULTS: A
      statistically significant difference (p = 0.027) was observed between the MPV of
      the stroke patients (8.6+/-1.95 fL) and the control group (7.93+/-0.82 fl). The
      MPV (9.24+/-1.98 fL) and CRP (10.8+/-7.0 mg/l) of those ischemic stroke patients
      who died were statistically significantly higher (p < 0.05) than the MPV (8.09+/
      1.75 fl) and CRP (3.2+/-3.5 mg/l) of the patients who survived. There was also a
      positive correlation between the MPV and CRP of the ischemic stroke patients (r =
      0.31, p = 0.029). CONCLUSIONS: The fact that there is a relationship between the
      MPV and CRP in ischemic stroke patients and that the CRP and MPV are higher in
      the ischemic stroke patients who died in comparison to those who survived may be
      an indication of the roles these markers play in the mortality of stroke
      patients.

PMID- 23852904
TI  - Supraorbital and infraorbital nerve blockade in migraine patients: results of 6
      month clinical follow-up.
AB  - BACKGROUND: Nerve blockades are used for the treatment of acute migraine episodes
      in emergency room conditions and beneficial results are obtained from this
      clinical use. Although this is the case, there are limited numbers of studies
      investigating the long-term effects of such an approach. PATIENTS AND METHODS: In
      this investigation, we had 26 patients diagnosed as migraine based on the ICHD II
      criteria, these were injected with 1% lidocaine at supraorbital and infraorbital
      nerve localizations and clinical results were evaluated after 6 months of follow
      up. All patients received 1.5 ml of 1% lidocaine bilaterally for supraorbital and
      infraorbital nerves with three day intervals for three times. Clinical evaluation
      was conducted by recording the number of migraine episodes per month together
      with migraine disability assessment scale (MIDAS) and visual analog scale (VAS)
      scores before and six months after the treatment. RESULTS:  Mean age of the
      patients recruited in the study was 31.1+/-10.2 years. Disease duration was 8.1+/
      5.4 years, the duration of the headache was 28.4+/-18.4 hours, mean number of
      episodes before treatment was 9.9+/-5.2, mean MIDAS was calculated as 3.2+/-0.8,
      and VAS as 9.0+/-1.0. Six months after the treatment, mean number of attacks was
      2.0+/-3.0, MIDAS was 1.4+/-0.9 and VAS was 3.5+/-3.6. There was a statistically
      significant difference between the results obtained before and after the
      treatment. CONCLUSIONS:  Injecting 1% of lidocaine to supraorbital and
      infraorbital nerve for three times prevents the acute migraine episodes
      effectively during the 6-months of follow-up without having any significant side
      effects.

PMID- 23852905
TI  - The effect of pulsed electromagnetic radiation from mobile phone on the levels of
      monoamine neurotransmitters in four different areas of rat brain.
AB  - BACKGROUND: The use of mobile phones is rapidly increasing all over the world.
      Few studies deal with the effect of electromagnetic radiation (EMR) on monoamine
      neurotransmitters in the different brain areas of adult rat. AIM: The aim of the
      present study was to investigate the effect of EMR on the concentrations of
      dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the hippocampus,
      hypothalamus, midbrain and medulla oblongata of adult rats. MATERIALS AND
      METHODS: Adult rats were exposed daily to EMR (frequency 1800 MHz, specific
      absorption rate 0.843 W/kg, power density 0.02 mW/cm2, modulated at 217 Hz) and
      sacrificed after 1, 2 and 4 months of daily EMR exposure as well as after
      stopping EMR for 1 month (after 4 months of daily EMR exposure). Monoamines were
      determined by high performance liquid chromatography coupled with fluorescence
      detection (HPLC-FD) using their native properties. RESULTS: The exposure to EMR
      resulted in significant changes in DA, NE and 5-HT in the four selected areas of
      adult rat brain. CONCLUSIONS: The exposure of adult rats to EMR may cause
      disturbances in monoamine neurotransmitters and this may underlie many of the
      adverse effects reported after EMR including memory, learning, and stress.

PMID- 23852906
TI  - Ischemic preconditioning reduces deep hypothermic circulatory arrest
      cardiopulmonary bypass induced lung injury.
AB  - PURPOSE: Ischemic preconditioning (IP) has been used to reduce ischemia
      reperfusion injury in several models. It remains unknown whether IP is sufficient
      to prevent deep hypothermic circulatory arrest (DHCA) cardiopulmonary bypass
      (CPB) induced lung injury. MATERIALS AND METHODS: Twenty-four piglets were
      randomly divided into four groups: routine CPB (CPB), CPB + DHCA (DHCA), CPB + IP
      + DHCA (IP-1) and CPB + hypoxia-ischemia preconditioning + DHCA (IP-2). Lung
      static compliance (Cstat) and pulmonary vascular resistance (PVR) were measured
      as indicators of lung function at three points during CPB. TNF-alpha, IL-8 and IL
      10 expressions were detected by radioimmunoassay. CD18 expression was determined
      by flow cytometer. Some lung tissues were excised to measure the wet/dry weight
      ratio (W/D) and some were fixed to observe pathological changes. RESULTS: Cstat
      significantly decreased whereas PVR increased in DHCA group. IP prevented DHCA
      induced lung functional impairment, especially IP-2 treatment. More cytokines
      were produced after CPB in all groups, but with varying level. Left
      atrium/pulmonary artery ratio of CD18 expression on monocytes decreased only in
      DHCA group, whereas which on polymorphonuclear neutrophils decreased in DHCA
      group, IP-1 group at 1h post-CPB and IP-2 group. Although lung W/D was increased
      in IP-2 group compared with pre-CPB, but significantly lower than that in DHCA
      group. Histological findings showed less lung injuries in IP groups than DHCA
      group. CONCLUSIONS: DHCA aggravates lung inflammatory injury and IP may reverse
      this injury. Maintaining ventilation with pulmonary artery perfusion in the lung
      IP process during CPB seems to be more superior to single pulmonary artery
      perfusion.

PMID- 23852908
TI  - Oral contraceptives and changes in nutritional requirements.
AB  - Oral contraceptives (OCs) are a major class of prescription drug, used by a large
      proportion of women starting from early adolescence. Much research has been
      conducted to investigate the physiological changes that occur in women who take
      OCs. These include changes in general health as well as in nutritional needs. In
      terms of nutrition, several studies investigated whether women on OCs need
      different amounts of some vitamins and minerals. In particular, a report from the
      World Health Organization (WHO) points out that the influence of OCs on nutrient
      requirements is a topic of high clinical relevance and should, therefore, receive
      great attention. It has been shown that the key nutrient depletions concern folic
      acid, vitamins B2, B6, B12, vitamin C and E and the minerals magnesium, selenium
      and zinc. Most research has focused on the levels of these vitamins and minerals
      in the blood of women who take OCs compared to women who do not. Since women who
      take OCs not always have adequate diet, may have unhealthy life style or may
      suffer from pathologies of malabsorption, the possibility to prevent vitamin and
      mineral deficiencies by taking appropriate dietary supplements should be
      considered a first-line approach by clinicians. 

PMID- 23852907
TI  - Identification of the hydration state in emergency patients: correlation between
      caval index and BUN/creatinine ratio.
AB  - BACKGROUND: Dehydration is a frequent clinical problem. No single laboratory
      value has been found to be accurate; however, the BUN/Creatinine Ratio appears
      the most sensitive parameter. The respiratory variation (Caval Index, CIn) in the
      diameter of the inferior vena cava has been investigated as a non-invasive marker
      for the intravascular volume status. AIM: The present study is performed with the
      aim to explore the relationship between CIn and BUN/creatinine ratio. PATIENTS
      AND METHODS: This prospective, observational study was conducted at Emergency
      Department (ED) of San Paolo Hospital (Savona, Italy), in October 2011. RESULTS:
      113 patients were considered eligible (mean age of 63 years). We found a good
      correlation between CIn and BUN/Cr Ratio (Pearson Index 0.76, p < 0.001).
      Receiver operator characteristic curve (ROC) analyses indicated that the maximum
      value was 0.884 (p < 0.0001) and corresponded to CIn 60.7%, (sensitivity 79%,
      specificity 89%). CIn was a good predictor for patients with BUN/Cr ratio greater
      than 20, and was particularly strong in determining patients with lower BUN/Cr
      ratio. DISCUSSION: Our study suggests that inferior vena cava could provide
      indications on the state of hydration of the patients: we found that a caval
      index greater than or equal to 60% was associated with a BUN/Cr Ratio over 20,
      which is considered an important marker for dehydration. Therefore, bedside
      sonography can give emergency physicians immediate information on patient volume
      status long before obtaining laboratory findings. CONCLUSIONS: Our study seems to
      support the hypothesis that CIn can be a useful bedside marker to predict
      dehydration in Emergency Department (ED) patients.

PMID- 23852909
TI  - Simultaneous administration of human acidic and recombinant less acidic follicle
      stimulating hormone for ovarian stimulation improves oocyte and embryo quality,
      and clinical outcome in patients with repeated IVF failures.
AB  - BACKGROUND: Ovarian stimulation is an integral procedure in assisted reproduction
      treatment. It is achieved by the administration of exogenous gonadotropins to
      increase follicular recruitment and oocyte yield. Optimization of ovarian
      stimulation is an essential prerequisite for the success of IVF treatment. AIM:
      This study aimed to evaluate the effect of a combined stimulation protocol of
      human FSH and recombinant FSH, simultaneously administered, on oocyte and embryo
      quality and clinical outcome. PATIENTS AND METHODS: In a prospective randomized
      study 197 infertile patients with a history of previous IVF failures for at least
      3-5 attempts, were enrolled for an in vitro fertilization treatment. All patients
      had a standard down-regulation with GnRH analog and were then stimulated with
      FSH. The patients were matched into three groups: group A (no = 66) received
      human FSH combined with recombinant FSH in equal doses, simultaneously
      administered; group B (no = 67) received human FSH alone and group C (no = 64)
      received recombinant FSH alone. RESULTS: There were significantly higher
      pregnancy (p < 0.04) and implantation rates (p < 0.03) in favor of group A
      (hFSH/rFSH) compared to groups B (hFSH) and C (rFSH). A significant increase in
      the proportion of mature metaphase II oocytes (p < 0.002) and grade 1 embryos (p
      < 0.03) was observed in group A with respect to group B and C. Significantly
      higher delivery rate (p < 0.01) was achieved in group A compared to groups B and
      C. No significant differences were observed between groups regarding miscarriage
      rate and risk of ovarian hyperstimulation syndrome. CONCLUSIONS: The results show
      that the combination of human and recombinant FSH for ovarian stimulation may
      produce a positive effect on follicular development as it improve oocyte quality,
      embryo development, and ultimately clinical outcome.

PMID- 23852910
TI  - First and second trimester biochemical markers in familial mediterranean fever.
AB  - OBJECTIVES: Our aim was to investigate whether the maternal serum concentrations
      of first and second trimester serum analytes are altered in familial
      Mediterranean fever (FMF) pregnancies. MATERIALS AND METHODS: The screening tests
      were compared in a series of 16 serum samples from FMF pregnancies and in a
      cohort of 48 pregnant women with normal pregnancy. Serum samples were obtained
      between 11 and 13 weeks; 16 and 18 weeks gestation. RESULTS: Serum pregnancy
      associated plasma protein-A (PAPP-A) levels, expressed as multiples of the median
      (0.9 +/- 0.45 MoM) in the control group, were significantly higher than FMF
      patients (0.6 +/- 0.3 MoM) (p = 0.027). Analyses of alpha-fetoprotein, human
      chorionic gonadotropin and oestriol levels showed no significant differences
      between FMF and normal pregnancies. CONCLUSIONS: Our study revealed that low
      levels of PAPP-A are associated with FMF.

PMID- 23852911
TI  - The role of serum N-terminal pro-brain natriuretic peptide in transient tachypnea
      of the newborn.
AB  - BACKGROUND AND OBJECTIVES: Transient tachypnea of the newborn (TTN), also known
      as wet lung disease, is a common cause of respiratory distress in the newborn. It
      has been demonstrated that, in alveolar type II cell cultures of the rat,
      receptors affected by the natriuretic peptides are expressed and that atrial
      natriuretic peptide (ANP) reduced amiloride-sensitive Na+ transport in these
      cells with a pattern similar to that in renal tubules, thereby inhibiting Na+ re
      absorption in a concentration-dependent manner. Brain natriuretic peptide (BNP)
      is known to act on these receptors and it is suggested that it may be involved in
      fluid absorption by the lungs. The present study aimed to investigate the role of
      BNP in the pathogenesis of transient tachypnea of the newborn. PATIENTS AND
      RESULTS: Serum NT-proBNP (N-terminal-proBNP) level measurements of 43 infants
      diagnosed with transient tachypnea of the newborn were compared to those of 29
      healthy neonates. There were no statistically significant differences in NT
      proBNP level between the study group and the control group. CONCLUSIONS: NT
      proBNP has no role in the pathophysiology of transient tachypnea of the newborn.
      Other factors which may potentially be involved in this etiology should be
      investigated.

PMID- 23852912
TI  - Association of the polymorphism of MMP2 with the risk and severity of lumbar disc
      degeneration in the Chinese Han population.
AB  - OBJECTIVE: The present study aimed to determine whether the -735 C/T polymorphism
      of the Matrix Metalloproteinase 2 (MMP2) gene is associated with the risk and
      severity of lumbar disc degeneration (LDD) in the Chinese Han population.
      PATIENTS AND METHODS: A total of 1008 patients with LDD and 906 healthy controls
      were enrolled in this study. The grade of disc degeneration was determined
      according to Schneiderman's classification for Magnetic Resonance Imaging (MRI).
      The -735 C/T polymorphism of MMP2 was genotyped using polymerase chain reaction
      and the restriction fragment length polymorphism method. RESULTS: The genotype
      frequency of the -735 C/T polymorphism was in agreement with the Hardy-Weinberg
      equilibrium (p = 0.087). The frequencies of the -735CT and TT genotypes were
      significantly lower among LDD patients compared with normal controls (p < 0.001);
      CT and TT genotype were significantly associated with a decreased risk of LDD
      compared with the CC genotype (for TT genotype, p = 0.031; OR 0.413; 95% CI 0.184
      0.924; for CT genotype, p < 0.001, OR 0.645, 95% CI 0.506-0.822). Patients with
      LDD showed significantly higher frequencies of the C allele than normal controls
      (p < 0.001), T allele was significantly associated with a decreased risk of LDD
      compared with the C allele (p < 0.001; OR 0.631; 95% CI 0.508-0.783). In
      addition, the -735TT and CT genotypes, as well as the T allele were associated
      with lower degenerative grades of LDD compared with CC genotype and the C allele,
      respectively (both p < 0.001). CONCLUSIONS: The -735 C/T polymorphism of MMP2 may
      be associated with the risk and severity of LDD in the Chinese Han population.

PMID- 23852913
TI  - Botulinum toxin treatment in glaucomatous patients: a pilot study.
AB  - PURPOSE: The purpose was to evaluate the efficacy of the treatment of iatrogenic
      entropion (IE), in patients affected by primary open angle glaucoma (POAG), by
      botulinum toxin injections (BTI). PATIENTS AND METHODS: 20 patients of the
      "Glaucoma Center" of the Hospital "Umberto I" (Rome) were examined. These
      patients had POAG and used prostaglandin analogues (PA). Mean age was 75.5 years
      old (range 68-83); they had been suffering from PAOG since 10 years and were not
      affected by other relevant systemic diseases. One to three BTI were made into the
      lower orbicularis muscle using a 0.3 G needle (0.025 to 0.05 units for each
      injection site). RESULTS: The results were particularly significant in 18 out of
      20 patients. Two patients showed slight improvements. A rating scale ranging from
      0 to 6 points (0 corresponded to 'no effect' and 6 to the 'complete' resolution
      of the entropion) was used to evaluate the goals of the treatment. The average
      rating was 5.37 points. CONCLUSIONS: The entropion due to glaucoma therapy with
      PA can be successfully treated with BTI in the orbicularis muscle, despite
      offering temporary therapeutic effects.

PMID- 23852914
TI  - Should ureteroscopy be considered as the first choice for proximal ureter stones
      of children?
AB  - OBJECTIVES: In this study, we aimed to analyze the ureter stones that had been
      treated using rigid ureteroscopy and pneumatic lithotripsy without mechanically
      dilating the ureteral orifice. PATIENTS AND METHODS: Records of 110 patients who
      had undergone rigid ureteroscopy and pneumatic lithotripsy due to ureteral stone
      between February 2005 and May 2011 were retrospectively analyzed. The location
      and size of the stone and additional anomalies in the urinary tract on the
      preoperative direct urinary system (DUS) X-Ray, urinary system ultrasonography
      (USG), intravenous pyelography (IVP) if performed, and computed tomography (CT),
      were found from the records of the patients. RESULTS: The mean age of the
      patients was 5.2 (range 1-17 years). 74 (67.2%) of the patients were males and 36
      (32.8%) were females. A total of 115 rigid ureteroscopies were performed on 110
      patients. 72 (65%) of the stones were located in the lower ureter, 21 (19%) were
      located in the middle part of the ureter, and 17 (15.4%) were located in the
      upper ureter. The mean stone size was determined as 7.5 mm (range 5-15). The mean
      stone size was determined as 7.4 mm in the lower ureter, as 8.3 mm in the middle
      ureter, and 8.4 mm in the upper ureter. No difference was found between the sizes
      of the stones in different locations (p = 0.121). The stone free rate was found
      as 92.2% for all ureteral stones. The total stone free rate according to the
      location of the stones was determined as 79.2% in the upper ureter, as 94.4% in
      the middle ureter and 93,8% in the lower ureter (p = 0.022). The total
      complication rate was 7.6%. Complication rates were 7.2%, 4.1% and 10.7% for the
      lower, middle and upper ureter, respectively (p = 0.411) (Table I). No difference
      was found in terms of complication rates according to location of the stone in
      the ureter. No major perioperative or postoperative complications developed. A
      double J stent was inserted in 36 (32%) patients for 2-3 weeks. CONCLUSIONS: We
      suggest that rigid ureteroscopy may be considered as the first choice for
      treatment of not only distal-middle ureter stones, but also for proximal ureter
      stones.

PMID- 23852915
TI  - Atomic carbide bonding leading to superior graphene networks.
AB  - A versatile method for achieving atomic carbide-bonded graphene networks on both
      metallic and non-metallic substrates is described. This consists of vacuum
      assisted thermal exfoliation and floatation of functional graphenes at elevated
      temperatures, followed by deposition on substrates and in situ formation of
      carbide bonds. The cross-linked graphene networks with an interlayer distance of
      angstroms exhibits a unique combination of unprecedented properties. 

PMID- 23852916
TI  - ESI hydrogen/deuterium exchange can count chemical forms of heteroatom-bound
      hydrogen.

PMID- 23852917
TI  - Quantitative biocompatibility evaluation of nickel-free high-nitrogen stainless
      steel in vitro/in vivo.
AB  - Coronary stents must not provoke an inflammatory response; however, some kinds of
      ions that are released from biometals induce biological reaction. In the present
      study, we quantitatively evaluated biological reaction of nickel-free high
      nitrogen stainless steel (HNS) by endothelial cell culture, and a bioimaging
      system using NF-kappaB/luciferase transgenic mice to confirm the potential of HNS
      for the application of coronary stent. Endothelialization was greater with HNS
      than with commercial stainless steel (SUS316L). In vivo inflammatory response of
      HNS was lower than that of SUS316L. These differences may be related to the
      amounts of nickel ion eluted from the stents, as HNS did not elute nickel ion.
      These data suggest that HNS may be useful as a material for coronary artery
      stents.

PMID- 23852918
TI  - Evaluation of nonscarred myocardial T1 value using contrast-enhanced look-locker
      cardiac MRI and its relationship to cardiac function in dilated cardiomyopathy:
      Comparison of 1.5 and 3.0 Tesla MRI.
AB  - PURPOSE: To assess relationship between nonscarred myocardial T1 value measured
      using contrast-enhanced Look-Locker MRI and cardiac function in dilated
      cardiomyopathy (DCM) at 1.5 Tesla (T) and 3.0T MRI. MATERIALS AND METHODS:
      Contrast-enhanced Look-Locker MRI was performed in 35 DCM patients. Nonscarred
      myocardial and blood T1 values were calculated from the signal intensity values
      and the delay time obtained on Look-Locker MRI. We assessed the correlation
      between the myocardial T1 value or myocardial T1 minus blood T1 value and cardiac
      function estimated using cine MRI (e.g., end-diastolic volume: EDV, left
      ventricular ejection fraction: LVEF) or brain natriuretic peptide (BNP). RESULTS:
      With 1.5T MRI (n = 16), the myocardial T1 value correlated negatively with the
      EDV(r = -0.66) and end-systolic volume (ESV; r = -0.68), and positively with the
      LVEF (r = 0.51); the myocardial T1 minus blood T1 value correlated inversely with
      EDV (r = -0.70), ESV (r = -0.62), and brain natriuretic peptide (BNP; r = -0.56).
      With 3.0T MRI (n = 17), the myocardial T1 value correlated negatively with ESV (r
      = -0.44), septal thickness (r = -0.60), and BNP (r = -0.51), and positively with
      LVEF (r = 0.61); the myocardial T1 minus blood T1 value negatively correlated
      with BNP (r = -0.50) and positively with LVEF (r = 0.54). CONCLUSION: The
      nonscarred myocardial T1 value measured with either 1.5T or 3.0T contrast
      enhanced Look-Locker MRI is significantly related to cardiac dysfunction in DCM.

PMID- 23852919
TI  - Silver nanoparticles impregnated alginate-chitosan-blended nanocarrier induces
      apoptosis in human glioblastoma cells.
AB  - Herein, a green method for the development of a novel biodegradable silver
      nanoparticles (NPs) impregnated alginate-chitosan-blended nanocarrier (Ag NPs-Alg
      Chi NC) is reported. The synthesis of Ag NPs-Alg-Chi NC is based on the
      polyelectrolyte complex formation between alginate and chitosan. The composite NC
      is characterized by ultraviolet-visible spectroscopy, transmission electron
      microscopy, scanning electron microscopy (SEM), Fourier transform infrared
      spectroscopy, and X-ray diffraction. The Ag NPs in the NC are found to elicit
      anticell proliferative effect on refractory U87MG (human glioblastoma) cells at
      IC50 of 2.4 MUg mL(-1) for Ag NPs. The cell cycle analysis shows extensive DNA
      damage. Elevation in reactive oxygen species level indicates induction of
      oxidative stress in treated cells. Mitochondrial dysfunction in cell death is
      evident from the depolarization of mitochondrial membrane potential (DeltaPsim ).
      Fluorescence and SEM images of the treated cells reveal nuclear and morphological
      changes characteristic of apoptosis, which is further confirmed by TUNEL assay.
      The induction of apoptosis at low concentration of Ag NPs present in Ag NPs-Alg
      Chi NC in comparison with free Ag NPs makes it a promising tool for cancer
      therapy.

PMID- 23852920
TI  - Base-dependent stereodivergent intramolecular aza-Michael reaction: asymmetric
      synthesis of 1,3-disubstituted isoindolines.
AB  - The nucleophilic addition (A(N)) / intramolecular aza-Michael reaction (IMAMR)
      process on Ellman's tert-butylsulfinyl imines, bearing a Michael acceptor in the
      ortho position, is studied. This reaction affords 1,3-disubstituted isoindolines
      with a wide range of substituents in good yields and diastereoselectivities.
      Interestingly, careful choice of the base for the aza-Michael step allows either
      the cis or the trans diastereoisomers to be exclusively obtained. This
      stereodivergent cyclization has enabled the synthesis of C2-symmetric bisacetate
      substituted isoindolines. In addition, bisacetate isoindolines bearing two well
      differentiated ester moieties are also noteworthy because they may allow for the
      orthogonal synthesis of beta,beta'-dipeptides using a single nitrogen atom as a
      linchpin.

PMID- 23852921
TI  - An attenuated temperature-sensitive strain of cytomegalovirus (tsm5) establishes
      immunity without development of CD8(+) T cell memory inflation.
AB  - Cytomegalovirus (CMV) is a widely prevalent herpesvirus that is well tolerated by
      an immune competent host yet establishes a state of chronic infection. The virus
      is thought to undergo frequent subclinical episodes of reactivation which leads
      to an unusually large accumulation of CMV-specific CD8(+) T lymphocytes in the
      peripheral blood, a phenomenon termed "memory inflation." The high magnitude of
      the CMV T cell response has been implicated in impaired immunity to heterologous
      pathogens such as EBV, influenza and West Nile virus. Here, using murine CMV
      (MCMV), we show that memory inflation of virus-specific CD8(+) T cells is avoided
      if mice are infected with a replication defective virus called temperature
      sensitive mutant 5 (tsm5), which carries an attenuating mutation within the DNA
      primase gene. Mice infected with tsm5 do generate primary T cell responses
      towards viral proteins but these do not amass to skew the memory repertoire of
      CD8(+) T cells. Therefore, attenuation of the virus replication machinery may be
      valuable in future CMV vaccine designs because the virus remains immunogenic but
      does not contribute to CMV associated T cell immune senescence.

PMID- 23852923
TI  - Elastic properties of human posterior eye.
AB  - This study examines the elastic properties of the human posterior retina,
      choroid, and sclera. Twenty-four human eyes from 30- to 74-year-old donors were
      obtained from an eye bank. Vertically and horizontally oriented tissue strips of
      the retina, choroid, and sclera (ideally n = 12 in each group) were harvested
      from the posterior eyes. Their thicknesses were estimated optically. The samples
      were stretched at 1 mm/s in 37 degrees C saline. Stress and strain were obtained
      from the mechanical tests, and then the transition stress, transition strain, toe
      modulus, and heel modulus were calculated. Statistical analysis was performed for
      comparison between groups. Linear regression analyses were used to explore the
      relationship between the mechanical parameters and age. We found that the stress
      strain relationship of the retina, choroid, and sclera were nonlinear. Except for
      the retinal transition strain (p = 0.0124), no statistical difference was found
      between the vertical and horizontal meridian in the mechanical parameters (p >
      0.05). Furthermore, weak relationship was observed between some of the mechanical
      parameters and the donors' age. Our results suggest that there is significant
      anisotropy in the retina, and mechanical properties of each layer may change with
      age.

PMID- 23852924
TI  - A comparison of the stress corrosion cracking susceptibility of commercially pure
      titanium grade 4 in Ringer's solution and in distilled water: a fracture
      mechanics approach.
AB  - From the results of laboratory investigations reported in the literature, it has
      been suggested that stress corrosion cracking (SCC) mechanisms may contribute to
      early failures in titanium alloys that have elevated oxygen concentrations.
      However, the susceptibility of titanium alloys to SCC in physiological
      environments remains unclear. In this study, a fracture mechanics approach was
      used to examine the SCC susceptibility of CP titanium grade 4 in Ringer's
      solution and distilled de-ionized (DI) water, at 37 degrees C. The study duration
      was 26 weeks, simulating the non-union declaration of a plated fracture. Four
      wedge loads were used corresponding to 86-95% of the alloy's ligament yield load.
      The longest cracks were measured to be 0.18 mm and 0.10 mm in Ringer's solution
      and DI water, respectively. SEM analysis revealed no evidence of extensive
      fluting and quasi-cleavage fracture features which, in literature reports, were
      attributed to SCC. We thus postulate that the Ringer's solution accelerated the
      wedge-loaded crack growth without producing the critical stresses needed to
      change the fracture mechanism. Regression analysis of the crack length results
      led to a significant best-fit relationship between crack growth velocity
      (independent variable) and test electrolyte, initial wedge load, and time of
      immersion of specimen in electrolyte (dependent variables).

PMID- 23852922
TI  - Cholinergic circuitry of the human nucleus basalis and its fate in Alzheimer's
      disease.
AB  - The nucleus basalis is located at the confluence of the limbic and reticular
      activating systems. It receives dopaminergic input from the ventral tegmental
      area/substantia nigra, serotonergic input from the raphe nuclei, and
      noradrenergic input from the nucleus locus coeruleus. Its cholinergic contingent,
      known as Ch4, provides the principal source of acetylcholine for the cerebral
      cortex and amygdala. More than half of presynaptic varicosities along its
      cholinergic axons make traditional synaptic contacts with cortical neurons.
      Limbic and paralimbic cortices of the brain receive the heaviest cholinergic
      input from Ch4 and are also the principal sources of reciprocal cortical
      projections back to the nucleus basalis. This limbic affiliation explains the
      role of the nucleus basalis in modulating the impact and memorability of incoming
      sensory information. The anatomical continuity of the nucleus basalis with other
      basomedial limbic structures may underlie its early and high vulnerability to the
      tauopathy and neurofibrillary degeneration of Alzheimer's disease. The tauopathy
      in Ch4 eventually leads to the degeneration of the cholinergic axons that it
      sends to the cerebral cortex. The early involvement of Ch4 has a magnifying
      effect on Alzheimer's pathology, because neurofibrillary degeneration in a small
      number of neurons can perturb neurotransmission in all cortical areas. Although
      the exact contribution of the Ch4 lesion to the cognitive changes of Alzheimer's
      disease remains poorly understood, the cholinergic circuitry of the nucleus
      basalis is emerging as one of the most strategically positioned and behaviorally
      consequential modulatory systems of the human cerebral cortex. J. Comp. Neurol.
      521:4124-4144, 2013. (c) 2013 Wiley Periodicals, Inc. 

PMID- 23852925
TI  - [Brachytherapy in men with prostate cancer: update on indications and outcomes].
AB  - Brachytherapy (BT), using either a low-dose-rate (LDR) or mostly high-dose-rate
      (HDR) technique, is the device able to deliver the highest dose-rate in the most
      conformal way. It is used as monotherapy or in combination with external beam
      radiotherapy (EBRT). LDR-BT is mostly used as monotherapy; HDR-BT is combined
      with EBRT +/- adjuvant hormone therapy. In patients with low-risk disease and in
      selected intermediate-risk patients, LDR-BT ensures long-term good disease
      control rates and HDR-BT can show similar results, even if with shorter follow
      up. In patients with intermediate/high risk disease the combination therapy (EBRT
      + HDR-BT) shows better oncological outcomes compared to EBRT monotherapy, even if
      the role of adjuvant hormone therapy is still unclear. Literature shows variable
      efficacy of BT in case of local recurrence after EBRT and radical prostatectomy
      even if few cases have been reported with short follow-up. Side effects are
      acceptable (urogenital toxicity, urinary incontinence, sexual function) and
      comparable with the other treatment modalities. So far, randomized controlled
      trials comparing the different treatment modalities are necessary to clarify
      indications and real efficacy.

PMID- 23852926
TI  - [Clinical use of the ImmunoCyt/uCyt+ and fluorescence in situ hybridisation
      (FISH) tests for urothelial carcinomas].
AB  - In recent decades years, we have witnessed the propagation and marketing of
      numerous diagnostic tests capable of detecting, in the urine of patients, the
      presence of urothelial tumor markers. Among None of the different markers studied
      to date , no one has been able to meet all the requirements of the ideal marker.
      We present and discuss below we discuss the results reported in the literature of
      about two tests approved by the Food and Drug Administration [ImmunoCyt/uCyt+ and
      Fluorescence In Situ Hybridisation (FISH)], which have been and commercially
      available for about 10 years., ImmunoCyt/uCyt + and Fluorescence In Situ
      Hybridisation (FISH).

PMID- 23852927
TI  - [Intravesical therapy with mitomycin through electromotive drug administration].
AB  - In the management of non-muscle invasive bladder cancer (NMIBC), high-level
      evidence supports the widespread practice of intravesical therapy with mitomycin
      C (MMC). Randomized trials showed a significant reduction in short-term
      recurrence compared with transurethral resection of bladder tumor (TURBT) alone,
      but little effect on long-term and no impact at all in preventing progression.
      Electromotive drug administration (EMDA(r)) offers a means of controlling and
      enhancing the tissue transport of certain drugs, in order to increase their
      efficacy. In both laboratory and clinical studies, intravesical electromotive
      drug administration (EMDA) increases MMC bladder uptake, resulting in an improved
      clinical efficacy in NMIBC without systemic side effects. New frameworks for
      treatment of NMIBC - e.g., sequential intravesical BCG and EMDA/MMC, as well as
      intravesical EMDA/MMC immediately before TURBT - have provided promising
      preliminary results with higher remission rates and longer remission times, and
      they are a priority to minimise the costs of disease management. These findings
      suggest EMDA-enhanced MMC efficacy against urothelial cancer could be a major
      therapeutic breakthrough in the treatment of NMIBC. 

PMID- 23852928
TI  - [Role of the combined regimen with local chemotherapy and Mw-induced hyperthermia
      for non-muscle invasive bladder cancer management. A systematic review].
AB  - OBJECTIVES: To give an updated review concerning the role of combined regimen
      (CT) based on microwave-induced hyperthermia (MwHT, CT-MwHT) with intravesical
      chemotherapy (ICT) as a treatment for non-muscle invasive bladder cancer
      (NMIBC).? EVIDENCE ACQUISITION: The review process followed the Preferred
      Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. An
      electronic search of the Medline, Embase, Cochrane Library, CancerLit, and
      ClinicalTrials.gov databases was undertaken. Relevant conference abstracts and
      urology journals were also included. The primary end-point was the time to
      recurrence. Secondary end-points included time to progression, bladder
      preservation rate, and adverse event (AE) rate.? EVIDENCE SYNTHESIS: A total of
      24 studies met inclusion criteria and underwent data extraction. When feasible,
      data were combined using random-effects meta-analytic techniques. Recurrence was
      seen 59% less after CT-MwHT than after MMC alone, however, due to the short
      follow-up, no definitive conclusions can be drawn about the impact on the time to
      recurrence and progression. The overall bladder preservation rate after CT-MwHT
      was 87.6%. This rate appeared higher than after MMC alone, but valid comparison
      studies could not be drawn due to the absence of randomized trials in neo
      adjuvant settings. AEs were higher with CT-MwHT than with MMC alone, but this
      difference was not statistically significant.? CONCLUSIONS: Published data
      suggest that recurrence rates for chemo-hyperthermia are substantially reduced
      compared with chemotherapy alone in adjuvant settings. Patients with refractory
      disease fare worse than those being treated with chemo-hyperthermia for their
      first tumor. Progression rates to muscle-invasive disease are markedly lower
      after combination treatment than after chemotherapy alone, with very high rates
      of bladder preservation. Tolerability is good, with few dropouts in the clinical
      trials. The results support CT-MwHT in the future as a standard procedure for
      high-risk recurrent patients, for subjects in whom the treatment with Bacillus
      Calmette-Guerin is contraindicated, and those unsuitable for radical cystectomy.

PMID- 23852929
TI  - [Innovative treatments of non muscle invasive bladder cancer].
AB  - Bladder cancer represents the second most common neoplasm of the urinary tract
      and the fourth in general among all the neoplastic pathologies for the male
      gender; in females, it is the eighth most frequent among all cancers. At the
      initial diagnosis, 70% of bladder tumors are non-muscle invasive. Treatment of
      this stage is multimodal, both surgical and pharmacological; the aim is not only
      to remove the tumor completely but also to prevent tumor recurrence and to
      inhibit its progression. The treatment for non-muscle invasive bladder cancer is
      a current topic in the scientific community and it is represented by the
      endoscopic resection of the tumor, which is generally followed by the adjuvant
      intravesical treatment with chemotherapy or immunotherapy agents, according to
      the different risk groups. Benefits and limits of intravesical therapies have
      been known for long; the aim of this study is to present new drugs or new
      treatment patterns which could emerge as a valid therapeutic alternative to
      conventional treatments, given the fact that, regardless of the type of
      treatment, 2/3 of the patients with a diagnosis of non-muscle invasive bladder
      cancer have a disease recurrence, and the 10-20% of these show a progression to a
      muscle-invasive tumor. Furthermore, the failure of intravesical therapy implies
      another therapeutic option, such as radical cystectomy for non-muscle invasive
      bladder cancer. According to this fact, new strategies include the activation of
      host immune system and the optimization of cytotoxic effects of chemotherapeutic
      drugs. Although most of these studies are still in a pre-clinical phase, the
      experimental outcomes and the initial results in humans are encouraging. 

PMID- 23852930
TI  - [Transurethral resection of bladder cancer: a simple and diffusely-performed
      technique but with controversial outcomes].
AB  - INTRODUCTION: Nowadays TUR is considered the golden standard for the diagnosis
      and treatment of NMIBC. However, TUR should be adequate: all bladder lesions
      should be resected and muscle must be present in the specimen in order to
      correctly stage the tumor. No bladder perforation should be performed and CIS
      diagnosed. TECHNIQUE: Bimanual palpation pre- and post-TUR should be encouraged,
      especially in teaching institutions. Urethroscopy should always precede the
      visualization of the bladder. All the visible tumors should be resected
      preferably with bipolar resectoscope, to avoid tissue charring and to facilitate
      the pathological diagnosis. The exophytic part of the tumor should be first
      resected and the fragment collected in a separate bottle. Tumor base must be
      biopsied with cold cup. Muscle must be present in the specimen. Fulguration of
      the tumor base and 1-2 cm around is of paramount importance. DISCUSSION: One of
      the most important parameters for evaluating the quality of TUR is tumor
      recurrence after 3 months. The EORTC GU Group showed that the 3-month recurrence
      varied from 0 to 46% between the European institutions participating in
      randomized prospective EORTC studies. This variability was not explained by the
      tumor characteristics nor by the adjuvant therapy administered, but by the poor
      quality of the TUR. The surgeon's performance and poor TUR quality were therefore
      suggested as being responsible for the results. A second EORTC study confirmed in
      fact that using a bladder diagram at the moment of diagnosis (signing the areas
      where the lesions are) and the presence of an experienced surgeon performing TUR
      were the two significant factors that could reduce the recurrence after 3 months.
      CONCLUSIONS: A complete, adequate first TUR is of paramount importance for the
      outcome of patients with NMIBC. It could be more important than any further
      adjuvant therapy administered.

PMID- 23852931
TI  - Witnessed sleep-related seizure and sudden unexpected death in infancy: a case
      report.
AB  - Witnessed reports of sudden death are rare, but critical to deciphering its
      mechanism(s). We report such a death in a seemingly healthy 8-month-old boy in
      whom seizures and respiratory distress in the prone position were witnessed upon
      discovery during a sleep period. Following cardiopulmonary resuscitation, anoxic
      encephalopathy resulted in "brain death" and withdrawal of life support after 2
      days. The autopsy did not reveal a primary anatomic cause of death. Metabolic
      evaluation failed to uncover an inborn error of ammonia, amino, organic, or fatty
      acid metabolism. Seizures in this case may have been secondary to cerebral
      hypoxia-ischemia complicating cardiorespiratory arrest of unknown etiology. Yet,
      they may represent the first manifestation of idiopathic epilepsy, triggering
      cardiopulmonary arrest, analogous to the terminal events postulated in sudden and
      unexplained death in epilepsy. This report alerts the forensic community to the
      possibility that sudden and unexplained death in infants may be due to seizures.

PMID- 23852932
TI  - An audit of the contribution to post-mortem examination diagnosis of individual
      analyte results obtained from biochemical analysis of the vitreous.
AB  - Biochemical analysis of the vitreous humor from the eye is an accepted accessory
      test for post-mortem investigation of cause of death. Modern biochemical
      analyzers allow testing of a range of analytes from a sample. However, it is not
      clear which analytes should be requested in order to prevent unnecessary testing
      (and expense). The means and standard deviation of the values obtained from
      analysis of the vitreous humor for sodium, potassium, chloride, osmolality,
      glucose, ketones (beta-hydroxybutyrate), creatinine, urea, calcium, lactate, and
      ammonia were calculated from which the contribution of each analyte was reviewed
      in the context of post-mortem findings and final cause of death. For sodium 32
      cases were regarded as high (more than one standard deviation above the mean),
      from which 9 contributed to post-mortem diagnosis [drowning (4), heat related
      death (2), diabetic hyperglycemia (2), and dehydration (1)], but 25 low values
      (greater than one standard deviation below the mean) made no contribution. For
      chloride 29 high values contributed to 4 cases--3 drowning and 1 heat-related,
      but these were all previously identified by a high sodium level. There were 29
      high and 35 low potassium values, none of which contributed to determining the
      final cause of death. Of 22 high values of creatinine, 12 contributed to a
      diagnosis of renal failure. From 32 high values of urea, 18 contributed to 16
      cases of renal failure (2 associated with diabetic hyperglycemia), 1 heat-related
      death, and one case with dehydration. Osmolarity contributed to 12 cases (5 heat
      related, 4 diabetes, 2 renal failure, and 1 dehydration) from 36 high values.
      There was no contribution from 32 high values and 19 low values of calcium and
      there was no contribution from 4 high and 2 low values of ammonia. There were 11
      high values of glucose, which contributed to the diagnosis of 6 cases of diabetic
      hyperglycemia and 21 high ketone levels contributed to 8 cases: 4 diabetic
      ketosis, 3 hypothermia, 3 ketosis of unknown cause, and 2 alcohol related deaths.
      A high lactate was identified in 25 cases, which contributed to 1 case with a
      diagnosis of metformin toxicity (1), but none of the 22 low lactate values
      contributed. The results of this audit have been used to reduce vitreous
      biochemistry test requests for sodium, osmolality, glucose, ketones, urea, and
      creatinine in most cases. Critical appraisal of each part of the post-mortem
      process should be undertaken to provide evidence to justify any investigative
      methods used in an autopsy.

PMID- 23852933
TI  - Kaempferol inhibits cancer cell growth by antagonizing estrogen-related receptor
      alpha and gamma activities.
AB  - Kaempferol is a dietary flavonoid that can function as a selective estrogen
      receptor modulator (SERM). Estrogen-related receptors alpha and gamma (ERRalpha
      and ERRgamma) are orphan nuclear receptors that play important roles in
      mitochondrial biogenesis and cancer development. We have shown that kaempferol
      can functionally antagonize the activities of ERRs based on both response element
      reporter systems and target gene analysis. Kaempferol modulation of mitochondrial
      function and suppression cancer cell growth has been confirmed. These findings
      suggest that kaempferol may exert their anti-cancer activities through
      antagonizing ERRs activities. 

PMID- 23852934
TI  - Doxorubicin conjugate of poly(ethylene glycol)-block-polyphosphoester for cancer
      therapy.
AB  - Polyphosphoesters with repeating phosphoester linkages in the backbone can be
      easily functionalized, are biodegradable and potentially biocompatible, and may
      be potential candidates as polymer carriers of drug conjugates. Here, the
      efficacy of a polyphosphoester drug conjugate as an anticancer agent in vivo is
      assessed for the first time. With controlled synthesis, doxorubicin conjugated to
      poly(ethylene glycol)-block-polyphosphoester (PPEH-DOX) via labile hydrazone
      bonds form spherical nanoparticles in aqueous solution with an average diameter
      of ~60 nm. These nanoparticles are effectively internalized by MDA-MB-231 breast
      cancer cells and release the conjugated doxorubicin in response to the
      intracellular pH of endosomes and lysosomes, resulting in significant
      antiproliferative activity in cancer cells. Compared with free doxorubicin
      injection, PPEH-DOX injection exhibits much longer circulation behavior in the
      plasma of mice and leads to enhanced drug accumulation in tumor cells. In an MDA
      MB-231 xenograft murine model, inhibition of tumor growth with systemic delivery
      of PPEH-DOX nanoparticles is more pronounced compared with free doxorubicin
      injection, suggesting the potential of polyphosphoesters as carriers of drug
      conjugates in cancer therapy. 

PMID- 23852935
TI  - Ultra-performance liquid-chromatography with tandem mass spectrometry for rapid
      analysis of pharmacokinetics, biodistribution and excretion of schisandrin after
      oral administration of Shengmaisan.
AB  - This study aimed to investigate the in vivo behaviors of the main components in
      traditional Chinese medicine (TCM) fomulae. The plasma pharmacokinetics, tissue
      distribution and excretion of the main component-schisandrin in rats after oral
      administration of a classical TCM prescription, shengmaisan (SMS), were studied
      by a developed and validated UPLC-MS/MS method. The separation of schisandrin was
      achieved on a UPLC HSS T3 column with a mobile phase consisting of acetonitrile
      and water at a flow rate of 0.5 mL/min by linear gradient elution. The MS/MS
      detection was carried out by monitoring the fragmentation of m/z 415.22 -> 384.26
      for schisandrin on a triple quadrupole mass spectrometer. The result showed that
      the method was suitable for the quantification of schisandrin in plasma, tissue
      and excreta samples with satisfactory selectivity, precision, accuracy,
      sensitivity, linearity and recovery. Pharmacokinetic results showed a rapid
      absorption phase with the mean Tmax of 0.17 h and a relatively slow elimination
      proceeding with a half-life (T1/2 ) of 5.24 +/- 1.28 h. The tissue distribution
      showed the maximum concentration distributions of schisandrin after oral
      administration of SMS were in the order of small intestine > large intestine >
      lung > liver > kidney > spleen > heart > brain. Only 0.005-0.006% of schisandrin
      was recovered in feces and was not detected in urine.

PMID- 23852936
TI  - A Bi2 WO6 -based hybrid photocatalyst with broad spectrum photocatalytic
      properties under UV, visible, and near-infrared irradiation.
AB  - Near-infrared active photocatalytic properties of Bi2 WO6 nanosheets owing to the
      oxygen vacancies of the Bi2 WO6 nanosheets are reported. The broad spectrum
      photocatalyst, Bi2 WO6 -TiO2 nanobelt heterostructures, are obtained by
      assembling Bi2 WO6 nanocrystals on TiO2 nanobelts. The active light band of the
      novel hybrid photocatalyst with high photocatalytic activity covers full-spectrum
      solar light including the UV, visible, and near-infrared ranges. 

PMID- 23852937
TI  - Defining quality outcomes for complex-care patients transitioning across the
      continuum using a structured panel process.
AB  - BACKGROUND: No standardised set of quality measures associated with transitioning
      complex-care patients across the various healthcare settings and home exists. In
      this context, a structured panel process was used to define quality measures for
      care transitions involving complex-care patients across healthcare settings.
      METHODS: A modified Delphi consensus technique based on the RAND method was used
      to develop measures of quality care transitions across the continuum of care.
      Specific stages included a literature review, individual rating of each measure
      by each of the panelists (n=11), a face-to-face consensus meeting, and final
      ranking by the panelists. RESULTS: The literature review produced an initial set
      of 119 measures. To advance to rounds 1 and 2, an aggregate rating of >75% of the
      measure was required. This analysis yielded 30/119 measures in round 1 and 11/30
      measures in round 2. The final round of scoring yielded the following top five
      measures: (1) readmission rates within 30 days, (2) primary care visit within 7
      days postdischarge for high-risk patients, (3) medication reconciliation
      completed at admission and prior to discharge, (4) readmission rates within 72 h
      and (5) time from discharge to homecare nursing visit for high-risk patients.
      CONCLUSIONS: The five measures identified through this research may be useful as
      indicators of overall care quality related to care transitions involving complex
      care patients across different healthcare settings. Further research efforts are
      called for to explore the applicability and feasibility of using the quality
      measures to drive quality improvement across the healthcare system.

PMID- 23852938
TI  - High cardiovascular risk profile in patients with sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: Sleep apnea is associated with hypertension and diabetes,
      putting these patients at high risk for developing cardiovascular disease. The
      goal of this study was to identify the individual cardiovascular risk profile and
      to detect premature and undiagnosed disease in patients with various degrees of
      sleep apnea. STUDY DESIGN: Cross-sectional. METHODS: Over a 6-month period, we
      consecutively characterized all patients referred to our sleep laboratory for an
      initial evaluation of sleep apnea. Clinical history; blood tests with oral
      glucose tolerance test, when appropriate; test for microalbuminuria; and an
      electrocardiogram (ECG) were performed. The Framingham general cardiovascular
      risk score was assessed in each patient. RESULTS: A total of 255 patients were
      evaluated. Of those, 190 (75%) were diagnosed with sleep apnea. Patients with
      sleep apnea had a significantly higher Framingham risk score than patients
      without sleep apnea. Adjusted for age and gender, severe sleep apnea was
      associated with a 60% increased cardiovascular risk compared with not having
      sleep apnea. In sleep apnea patients without previously diagnosed hypertension,
      an additional 45% had significant elevated blood pressure. Among sleep apnea
      patients without known diabetes, we tested 48% with a pathological glucose
      disposal. Twenty percent of sleep apnea patients without known heart disease had
      significant ECG changes. CONCLUSIONS: High Framingham score, undiagnosed
      hypertension, and pathological glucose disposal were highly prevalent in patients
      with sleep apnea. Appropriate screening routines are important to detect
      cardiovascular risk factors in patients with sleep apnea.

PMID- 23852940
TI  - Long-term care services expenditure projection in South Korea from 2015 to 2050.
AB  - South Korea has been undergoing significant change in its population structure
      over the past three decades. Within 10 years, South Korean baby-boomers will
      reach the age of 65 years and accelerate this change. This trend in population
      structure is crucial, because an aging population may increase medical demand,
      especially that for long-term care (LTC) services, which would create a financial
      burden on society. This study estimates total LTC expenditure in South Korea from
      2015 to 2050 by modifying the method proposed by the UK Personal Social Science
      Research Unit, the seminal study on projecting costs of LTC services. Using
      population data from the projections of the Korean Statistical Information
      Service, I stratify the projected population by gender and age, using the groups
      65-69, 70-74, 75-79 and 80 or over and divide LTC services into two categories,
      namely facility and home care. South Korea's total LTC expenditure is predicted
      to continuously increase and then reach 4.2% of GDP in 2050. Expenditure on LTC
      services for women is higher than that for men. Moreover, the increase in total
      expenditure is dramatic after 2040 for home-based services but is constant for
      facility services. This study shows that the presence of baby-boomers heavily
      influences LTC expenditure in South Korea.

PMID- 23852941
TI  - Direct detection of a persistent carbonyloxyl radical in the gas phase.

PMID- 23852939
TI  - Cell-penetrating peptides: achievements and challenges in application for cancer
      treatment.
AB  - One of the major hurdles to cure cancer lies in the low potency of currently
      available drugs, which could eventually be solved by using more potent
      therapeutic macromolecules, such as proteins or genes. However, although these
      macromolecules possess greater potency inside the cancer cells, the barely
      permeable cell membrane remains a formidable barrier to exert their efficacy. A
      widely used strategy is to use cell penetrating peptides (CPPs) to improve their
      intracellular uptake. Since the discovery of the first CPP, numerous CPPs have
      been derived from natural or synthesized products. Both in vitro and in vivo
      studies have demonstrated that those CPPs are highly efficient in transducing
      cargoes into almost all cell types. Therefore, to date, CPPs have been widely
      used for intracellular delivery of various cargoes, including peptides, proteins,
      genes, and even nanoparticles. In addition, recently, based on the successes of
      CPPs in cellular studies, their applications in vivo have been actively pursued.
      This review will focus on the advanced applications of CPP-based in vivo delivery
      of therapeutics (e.g., small molecule drugs, proteins, and genes). In addition,
      we will highlight certain updated applications of CPPs for intracellular delivery
      of nanoparticulate drug carriers, as well as several "smart" strategies for tumor
      targeted delivery of CPP-cargoes.

PMID- 23852942
TI  - Osteoconductivity and biodegradation of synthetic bone substitutes with different
      tricalcium phosphate contents in rabbits.
AB  - Various synthetic bone substitutes have been developed to reconstruct the bony
      defects that clinicians often encounter during surgical procedures. Among various
      synthetic bone substitutes, calcium phosphate (Ca-P) ceramics have been
      investigated because their composition and structure are similar to those of
      human bone. We evaluated the bone healing and biodegradation patterns of three
      types of Ca-P ceramic particle with various hydroxyapatite (HA)/beta-tricalcium
      phosphate (beta-TCP) weight ratio: pure beta-TCP, biphasic Ca-P (BCP) with a
      HA/beta-TCP weight ratio of 60/40 (BCP 60/40), and BCP with an HA/beta-TCP weight
      ratio of 20/80 (BCP 20/80). Four 8-mm-diameter defects were created in ten
      rabbits. Three of the defects in each rabbit were separately and randomly filled
      with one of the three experimental Ca-P ceramic particles, and the fourth was
      filled with blood clots (control). The specimens were harvested at 2 and 8 weeks
      post-surgery. The histologic and histometric findings revealed that the augmented
      space and new bone formation were significantly better for all three Ca-P
      ceramics than for the control group at both 2 and 8 weeks (p < 0.05). Compared to
      the pure beta-TCP, the two BCP groups were found to provide a larger amount of
      newly formed bone and bone density at the 2- and 8-week post-operative periods (p
      < 0.05). Throughout the observation period, BCP 60/40 and BCP 20/80 exhibited a
      similar bone healing and biodegradation patterns with regard to both individual
      particles and the total augmented area in vivo.

PMID- 23852943
TI  - Serotonin-immunoreactive sensory neurons in the antenna of the cockroach
      Periplaneta americana.
AB  - The antennae of insects contain a vast array of sensory neurons that process
      olfactory, gustatory, mechanosensory, hygrosensory, and thermosensory
      information. Except those with multimodal functions, most sensory neurons use
      acetylcholine as a neurotransmitter. Using immunohistochemistry combined with
      retrograde staining of antennal sensory neurons in the cockroach Periplaneta
      americana, we found serotonin-immunoreactive sensory neurons in the antenna.
      These were selectively distributed in chaetic and scolopidial sensilla and in the
      scape, the pedicel, and first 15 segments of the flagellum. In a chaetic
      sensillum, A single serotonin-immunoreactive sensory neuron cohabited with up to
      four serotonin-negative sensory neurons. Based on their morphological features,
      serotonin-immunopositive and -negative sensory neurons might process
      mechanosensory and contact chemosensory modalities, respectively. Scolopidial
      sensilla constitute the chordotonal and Johnston's organs within the pedicel and
      process antennal vibrations. Immunoelectron microscopy clearly revealed that
      serotonin-immunoreactivities selectively localize to a specific type of
      mechanosensory neuron, called type 1 sensory neuron. In a chordotonal scolopidial
      sensillum, a serotonin-immunoreactive type 1 neuron always paired with a
      serotonin-negative type 1 neuron. Conversely, serotonin-immunopositive and 
      negative type 1 neurons were randomly distributed in Johnston's organ. In the
      deutocerebrum, serotonin-immunoreactive sensory neuron axons formed three
      different sensory tracts and those from distinct types of sensilla terminated in
      distinct brain regions. Our findings indicate that a biogenic amine, serotonin,
      may act as a neurotransmitter in peripheral mechanosensory neurons.

PMID- 23852944
TI  - Fifteen minute consultation: headache in children under 5 years of age.
AB  - Headache occurring in children under the age of 5 years may cause a high level of
      anxiety in both parents and medical professionals. Crucial to a consultation
      about this problem will be to actively seek out clues to sinister pathologies,
      and investigate or reassure as appropriate. Making a positive diagnosis of a
      primary headache disorder where one exists is also important; however, in young
      children, headache does not always conform to well-established diagnostic
      criteria. This short guide provides a practical overview using the scenario of a
      new referral to the outpatient clinic. 

PMID- 23852945
TI  - High rates of quinolone-resistant strains of Shigella sonnei in HIV-infected MSM.
AB  - PURPOSE: There is increasing evidence that shigellosis is a predominantly
      sexually transmitted disease among men who have sex with men (MSM) and that
      infection with the human immunodeficiency virus (HIV) is a risk factor for
      shigellosis. METHODS: Retrospective analysis of antibiotic resistance profiles of
      Shigella species isolated from stool specimens of patients presenting with
      diarrhea from January 2010 to July 2012 in three German outpatient clinics
      specialized in HIV care. RESULTS: Among 79 cases of Shigella sonnei, 56 occurred
      in HIV-infected MSM, while 23 were observed in HIV-negative MSM. High resistance
      rates (>90%) were found for doxycycline, tetracycline, aminoglycosides, all
      cephalosporins of first and second generations tested, and
      trimethoprim/sulfamethoxazole. In total, 54% of cases were resistant to
      ciprofloxacin. Compared to negative subjects, HIV-infected MSM had a
      significantly higher rate of quinolone resistance. For ciprofloxacin, the
      resistance rates were 66 versus 24%, respectively (p = 0.0016). Individual
      resistance patterns did not indicate that this was due to a limited outbreak.
      Rates of resistance to other antibiotics than quinolones showed no differences
      between HIV-infected and HIV-negative cases. No resistance was found for
      carbapenems or newer cephalosporins such as ceftriaxone. CONCLUSIONS: The high
      rates of S. sonnei isolates resistant to quinolones and other traditional
      antibiotics are of concern. Innovative prevention efforts are urgently needed.
      The empirical use of quinolones in HIV-infected patients presenting with S.
      sonnei infection is no longer recommended.

PMID- 23852946
TI  - Kinetic resolution and stereoselective synthesis of 3-substituted aspartic acids
      by using engineered methylaspartate ammonia lyases.
AB  - Enzymatic amino acid synthesis: Kinetic resolution and asymmetric synthesis of
      various valuable 3-substituted aspartic acids, which were obtained in fair to
      good yields with diastereomeric ratio values of up to >98:2 and enantiomeric
      excess values of up to >99 %, by using engineered methylaspartate ammonia lyases
      are described. These biocatalytic methodologies for the selective preparation of
      aspartic acid derivatives appear to be attractive alternatives for existing
      chemical methods. 

PMID- 23852947
TI  - Efficacy and safety of telbivudine therapy in liver failure patients with chronic
      hepatitis B virus infection.
AB  - The objective of this study was to evaluate the short-term efficacy and safety of
      telbivudine therapy as compared to lamivudine therapy in liver failure patients
      with chronic hepatitis B virus (HBV) infection. These data were collected from 38
      liver failure patients with chronic HBV infection who were randomly enrolled to
      one of the two treatments. All patients received comprehensive treatments; 20
      patients were treated with telbivudine, and the other 18 patients were treated
      with lamivudine. The serum levels of HBV DNA, alanine aminotransferase, total
      bilirubin, prothrombin time activity, and creatine kinase were determined every 7
      days for 8 weeks. The results showed that the serum HBV DNA levels in patients
      treated with either telbivudine or with lamivudine declined gradually after the
      2nd week of treatment. However, HBV DNA levels in the telbivudine group fell to
      the lower limit of detection (<5+E2 copies/ml) after the 5th week, which was more
      rapid than in the lamivudine group. In addition, the total bilirubin and
      prothrombin time activity of the patients with telbivudine treatment showed a
      more significant improvement as compared to the patients treated with lamivudine
      from the start of the 5th week. All patients tolerated telbivudine or lamivudine
      treatment well. The patients treated with telbivudine did not have elevated serum
      creatine kinase or myopathic symptoms during the 8-week treatment period. Thus,
      telbivudine treatment is superior to lamivudine treatment in improving the
      condition of patients with liver failure as a result of chronic HBV infection in
      the short term.

PMID- 23852948
TI  - Cyclooxygenase 2 genetic polymorphism may increase the risk of developing
      leukoaraiosis in Chinese.
AB  - Cyclooxygenase-2 (COX-2) is a key enzyme involved in the conversion of
      arachidonic acid into prostaglandins, which are important mediators of
      inflammation. To clarify the role of inflammation in the pathogenesis of cerebral
      small vessel disease (SVD), we investigate the possible modulating effect of the
      functional COX-2 polymorphisms -1195G > A (rs689466) and -765G > C (rs20417) on
      the risk for development of cerebral SVD in a Chinese population. Genomic DNA of
      116 patients with lacunar infarction (LI), 334 patients with leukoaraiosis (LA)
      and 450 control subjects was genotyped for the COX-2 -1195G > A and -765G > C
      polymorphisms using polymerase chain reaction-restriction fragment length
      polymorphism. Distribution of genotypes and haplotypes in patients and controls
      were compared. The genotype distribution of the -765G > C polymorphism was not
      different between the patients with LI or LA and the control group. The 1195A
      allele carriers was identified independently to be related with LA (adjusted OR =
      1.41, 95 % confidence interval (CI) = 1.09-2.10, P = 0.03) but not associated
      with LI. The linkage disequilibrium analysis showed that -1195G > A and -765G > C
      SNPs are moderate linkage disequilibrium in this study population (D' = 0.70,
      r(2) = 0.16). Compared with G-1195-G-765 haplotype, the haplotype of A-1195-G-765
      showed significantly increased the risk of LA (OR = 1.24, 95 % CI = 1.10-1.55, P
      = 0.04) but not LI. In conclusion, we found that -1195G > A polymorphism and A
      1195-G-765 haplotype of COX-2 were associated with susceptibility to LA in a
      Chinese population.

PMID- 23852949
TI  - Mitochondria and tumor progression in ulcerative colitis.
AB  - BACKGROUND: The role of mitochondria in cancer is poorly understood. Ulcerative
      colitis (UC) is an inflammatory bowel disease that predisposes to colorectal
      cancer and is an excellent model to study tumor progression. Our goal was to
      characterize mitochondrial alterations in UC tumorigenesis. METHODS:
      Nondysplastic colon biopsies from UC patients with high-grade dysplasia or cancer
      (progressors; n = 9) and UC patients dysplasia free (nonprogressors; n = 9) were
      immunostained for cytochrome C oxidase (COX), a component of the electron
      transport chain, and were quantified by multispectral imaging. For six additional
      progressors, nondysplastic and dysplastic biopsies were stained for COX and
      additional mitochondrial proteins including PGC1alpha, the master regulator of
      mitochondrial biogenesis. Mitochondrial DNA (mtDNA) copy number was determined by
      quantitative polymerase chain reaction. Generalized estimating equations with two
      sided tests were used to account for correlation of measurements within
      individuals. RESULTS: Nondysplastic biopsies of UC progressors showed
      statistically significant COX loss compared with UC nonprogressors by generalized
      estimating equation (-18.5 units, 95% confidence interval = -12.1 to -24.9; P <
      .001). COX intensity progressively decreased with proximity to dysplasia and was
      the lowest in adjacent to dysplasia and dysplastic epithelium. Surprisingly, COX
      intensity was statistically significantly increased in cancers. This bimodal
      pattern was observed for other mitochondrial proteins, including PGC1alpha, and
      was confirmed by mtDNA copy number. CONCLUSIONS: Mitochondrial loss precedes the
      development of dysplasia, and it could be used to detect and potentially predict
      cancer. Cancer cells restore mitochondria, suggesting that mitochondria are
      needed for further proliferation. This bimodal pattern might be driven by
      transcriptional regulation of mitochondrial biogenesis by PGC1alpha.

PMID- 23852950
TI  - Role of the oxidative DNA damage repair gene OGG1 in colorectal tumorigenesis.
AB  - Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH
      predispose to colorectal adenomas and colorectal carcinoma (CRC) with high
      penetrance. We investigated whether rare inherited variants in other oxidative
      DNA damage repair genes predisposed to CRC. Single marker association analyses
      were assessed under an allelic model with Bonferroni correction for multiple
      testing. All statistical tests were two-sided. A rare inherited nonsynonymous
      variant in OGG1 (Gly308Glu), the functional partner of MUTYH, was over
      represented in case patients with advanced CRC compared with population-based
      control subjects (n = 36 of 2142 case patients vs n = 15 of 2175 control subjects
      in the training phase, P = 1.8*10(-3); and n = 22 of 1005 case patients vs n = 8
      of 1389 control subjects in the validation phase, P = 4.8*10(-4); P = 1.4*10(-5)
      combined; odds ratio = 2.92, 95% confidence interval = 1.80 to 4.74). Glycine at
      residue 308 was highly conserved through evolution, and the glutamic acid
      substitution was predicted as likely to interfere with function. Biallelic
      inherited and somatic OGG1 mutations were rarely observed in OGG1 (Gly308Glu)
      carriers, nor did we find any associated somatic mutator phenotype. These data
      suggest that OGG1 (Gly308Glu) may act as a low-penetrance allele that contributes
      to colorectal tumorigenesis. 

PMID- 23852952
TI  - MHC class I antigen processing and presenting machinery: organization, function,
      and defects in tumor cells.
AB  - The surface presentation of peptides by major histocompatibility complex (MHC)
      class I molecules is critical to all CD8(+) T-cell adaptive immune responses,
      including those against tumors. The generation of peptides and their loading on
      MHC class I molecules is a multistep process involving multiple molecular species
      that constitute the so-called antigen processing and presenting machinery (APM).
      The majority of class I peptides begin as proteasome degradation products of
      cytosolic proteins. Once transported into the endoplasmic reticulum by TAP
      (transporter associated with antigen processing), peptides are not bound randomly
      by class I molecules but are chosen by length and sequence, with peptidases
      editing the raw peptide pool. Aberrations in APM genes and proteins have
      frequently been observed in human tumors and found to correlate with relevant
      clinical variables, including tumor grade, tumor stage, disease recurrence, and
      survival. These findings support the idea that APM defects are immune escape
      mechanisms that disrupt the tumor cells' ability to be recognized and killed by
      tumor antigen-specific cytotoxic CD8(+) T cells. Detailed knowledge of APM is
      crucial for the optimization of T cell-based immunotherapy protocols. 

PMID- 23852951
TI  - Fifteenth biannual report of the Cochrane Haematological Malignancies Group-
      focus on non-Hodgkin's lymphoma.
AB  - This fifteenth biannual report of the Cochrane Haematological Malignancies Group
      (CHMG) highlights recently published randomized controlled trials (RCTs) in the
      field of hemato-oncology, covering the publication period from October 2011 to
      May 2012. Implications for clinical practice and methodological aspects are the
      main principles for selecting trials for this report. Studies were identified by
      electronic search of MEDLINE using a broad search filter that covers all topics
      in hemato-oncology combined with a highly sensitive search filter for randomized
      trials (Cochrane Handbook for Systematic Reviews of Interventions). 

PMID- 23852953
TI  - Enhanced chondrogenesis through specific growth factors in a buffalo embryonic
      stem cell model.
AB  - Chondrogenic differentiation of embryonic stem cells (ESCs) via embryoid bodies
      (EBs) is an established model to investigate chondrogenesis signaling pathways
      and molecular mechanisms in vitro. Our aim has been to improve upon the number of
      differentiated cells needed for the in vitro development of functional cartilage.
      Chondrogenic differentiation of buffalo ESCs was modulated by bone morphogenetic
      protein 2 (BMP-2), fibroblast growth factor 10 (FGF-10), transforming growth
      factor-beta1 (TGF-beta1 ) individually and their combination. ESCs
      differentiation into chondrocytes was characterized by the appearance of Alcian
      blue-stained nodules and the expression of cartilage-associated genes (RT-PCR)
      and protein (immunocytochemistry). BMP-2 or FGF-10 treatment enhanced
      chondrogenic differentiation, whereas TGF-beta1 treatment inhibited buffalo ESC
      derived chondrogenesis. The combination of BMP-2 and FGF-10 was the most
      effective treatment. This treatment resulted in a higher number of Alcian blue
      positive nodules by 15.2-fold, expression of the mesenchymal cell marker
      scleraxis gene by 3.25-fold, and the cartilage matrix protein collagen II gene
      and protein 1.9- and 7-fold, respectively, compared to the untreated control
      group. Chondrogenesis was also recapitulated from mesenchymal and chondrogenic
      progenitor cells, resulting in the establishment of mature chondrocytes. Thus,
      buffalo ESCs can be successfully triggered in vitro to differentiate into
      chondrocyte-like cells by specific growth factors, which may provide a novel in
      vitro model for further investigation of the regulatory mechanism(s) involved. 

PMID- 23852954
TI  - Determination of pseudo-ginsenoside GQ in human plasma by high performance liquid
      chromatography-tandem mass spectrometry.
AB  - A specific, sensitive and rapid method based on high performance liquid
      chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was developed for
      the determination of pseudo-ginsenoside GQ in human plasma. Liquid-liquid
      extraction was used to isolate the analyte from biological matrix followed by
      injection of the extracts onto a C8 column with isocratic elution. Detection was
      carried out on a triple quadrupole tandem mass spectrometer (API-4000 system) in
      multiple reaction monitoring mode using negative electrospray ionization. The
      mobile phase consisted of methanol-10 mM ammonium acetate (90:10, v/v) and the
      flow rate was 0.3 mL/min. The method was validated over the concentration range
      of 5.0-5000.0 ng/mL for plasma. Inter- and intra-day precisions (relative
      standard deviation) were all within 15% and the accuracy (relative error) was <=
      9.4%. The lower limit of quantitation was 5.0 ng/mL. The pseudo-ginsenoside GQ
      was stable after 8 h at room temperature, 24 h at autosampler and three freeze
      thaw cycles (from -30 to 25  degrees C). The method was successfully applied to
      the pharmacokinetic study of pseudo-ginsenoside GQ in healthy Chinese volunteers.

PMID- 23852956
TI  - Refining the interpretation of near-infrared band shapes in a polyynediyl
      molecular wire.
AB  - Spinning to improve (band) shape: A blend of theoretical and experimental work
      demonstrates that the rotational conformation of mixed-valence complexes
      influences the low-energy (NIR) transitions in such molecules. Interpretations of
      the NIR band shapes are presented. 

PMID- 23852957
TI  - Nickel-catalysed hydroalkoxylation reaction of 1,3-butadiene: ligand controlled
      selectivity for the efficient and atom-economical synthesis of alkylbutenyl
      ethers.
AB  - The nickel-catalysed hydroalkoxylation of butadiene is promoted by a
      nickel(0)/dppb catalyst (dppb = 1,4-bis(diphenylphosphino)butane; see scheme). By
      following this new synthetic procedure, alkylbutenyl ethers are readily obtained
      from an alcohol and 1,3-butadiene with exclusion of dimerisation and
      telomerisation products.

PMID- 23852958
TI  - CNT@Fe3O4@C coaxial nanocables: one-pot, additive-free synthesis and remarkable
      lithium storage behavior.
AB  - By using carbon nanotubes (CNTs) as a shape template and glucose as a carbon
      precursor and structure-directing agent, CNT@Fe3O4@C porous core/sheath coaxial
      nanocables have been synthesized by a simple one-pot hydrothermal process.
      Neither a surfactant/ligand nor a CNT pretreatment is needed in the synthetic
      process. A possible growth mechanism governing the formation of this
      nanostructure is discussed. When used as an anode material of lithium-ion
      batteries, the CNT@Fe3O4@C nanocables show significantly enhanced cycling
      performance, high rate capability, and high Coulombic efficiency compared with
      pure Fe2O3 particles and Fe3O4/CNT composites. The CNT@Fe3O4@C nanocables deliver
      a reversible capacity of 1290 mA h g(-1) after 80 cycles at a current density of
      200 mA g(-1), and maintain a reversible capacity of 690 mA h g(-1) after 200
      cycles at a current density of 2000 mA g(-1). The improved lithium storage
      behavior can be attributed to the synergistic effect of the high electronic
      conductivity support and the inner CNT/outer carbon buffering matrix.

PMID- 23852959
TI  - Synthesis of cationic R2P5(+) cages and subsequent chalcogenation reactions.
AB  - Cationic R2P5(+) cage compounds (1(+)) have been synthesized by the
      stoichiometric reaction of R2PCl, GaCl3 and P4. The reaction conditions depend on
      the substituent R. Alkyl-substituted derivatives (1 a-1 d[GaCl4]) are best
      synthesized under solvent-free conditions, whereas aryl-substituted derivatives
      (1 e-1 h[GaCl4]) are formed in C6H5F. All compounds have been prepared on a multi
      gram scale in good to excellent yields and have been fully characterized with an
      emphasis on (31P NMR spectroscopy in solution and single-crystal structure
      determination. Subsequent chalcogenation reactions of cations R2P5(+) (1 a(+), 1
      e(+)) and trication Ph6P7(3+) (3(3+)) with elemental sulfur (alpha-S8) or grey
      selenium (Se(grey)) yielded a series of unique polyphosphorus-chalcogen cations
      (4 a(+), 4 e(+), 5 a(+), 6(2+) and 7(2+)), possessing nortricyclane-type
      molecular structures. An in-depth study of the (31)P{(1)H} and (77)Se NMR
      spectroscopic parameters is presented, and correlations between the substitution
      pattern and the observed structural features have been investigated in detail.

PMID- 23852960
TI  - Tetra(p-tolyl)borate-functionalized solvent polymeric membrane: a facile and
      sensitive sensing platform for peroxidase and peroxidase mimetics.
AB  - The determination of peroxidase activities is the basis for enzyme-labeled
      bioaffinity assays, peroxidase-mimicking DNAzymes- and nanoparticles-based
      assays, and characterization of the catalytic functions of peroxidase mimetics.
      Here, a facile, sensitive, and cost-effective solvent polymeric membrane-based
      peroxidase detection platform is described that utilizes reaction intermediates
      with different pKa values from those of substrates and final products. Several
      key but long-debated intermediates in the peroxidative oxidation of o
      phenylenediamine (o-PD) have been identified and their charge states have been
      estimated. By using a solvent polymeric membrane functionalized by an appropriate
      substituted tetraphenylborate as a receptor, those cationic intermediates could
      be transferred into the membrane from the aqueous phase to induce a large
      cationic potential response. Thus, the potentiometric indication of the o-PD
      oxidation catalyzed by peroxidase or its mimetics can be fulfilled. Horseradish
      peroxidase has been detected with a detection limit at least two orders of
      magnitude lower than those obtained by spectrophotometric techniques and
      traditional membrane-based methods. As an example of peroxidase mimetics, G
      quadruplex DNAzymes were probed by the intermediate-sensitive membrane and a
      label-free thrombin detection protocol was developed based on the catalytic
      activity of the thrombin-binding G-quadruplex aptamer. 

PMID- 23852961
TI  - Cholesterol-/estradiol-appended alkynylplatinum(II) complexes as supramolecular
      gelators: synthesis, characterization, photophysical and gelation studies.
AB  - A series of cholesterol-/estradiol-appended alkynylplatinum(II) complexes with
      tridentate N-donor ligands, based on 2,6-bis(1-alkylpyrazol-3-yl)pyridine, has
      been synthesized and characterized by (1)H NMR spectroscopy, FAB-mass
      spectrometry, and elemental analysis. Their photophysical properties have also
      been investigated. Computational studies have been performed to provide insights
      into the nature of the electronic transitions. Some of the complexes have been
      found to form stable thermo- and mechanoresponsive supramolecular gels.

PMID- 23852962
TI  - Cytokine correlation between sinus tissue and nasal secretions among chronic
      rhinosinusitis and controls.
AB  - OBJECTIVES/HYPOTHESIS: Compare cytokine levels in sinus tissue to sinus
      secretions from controls and chronic rhinosinusitis patients. STUDY DESIGN: In
      vitro. METHODS: Polyurethane foam sponges were placed into middle meati of
      patients with chronic rhinosinusitis without nasal polyps (CRSsNP), with polyps
      (CRSwNP), and controls. Sinus biopsies were then taken from the same location.
      Protein levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN
      gamma), and interleukins (IL) 2, 4, 6, 8, 10, and 17A were measured via
      cytometric bead assay for each sample. Protein values from sinus tissue and
      secretions were compared with Pearson's correlation between samples as well as
      one-way ANOVA with posthoc t test between groups. RESULTS: Samples from 43
      patients in total were examined. Mucus was measured from 10 controls, 11 CRSsNP
      and 10 CRSwNP, and sinus tissue was measured from 10 controls, 15 CRSsNP and 10
      CRSwNP. IL-8 and IFN-gamma levels were outside of the detectable range of the
      assay. Levels of secreted IL-2, 4, 6, 10, and 17A correlated with tissue levels
      (P < 0.05 for all, r > 0.49) while TNF-alpha did not (P = 0.71). CRSsNP had
      elevated mucus levels of IL-2, 4, 6, 10, and 17A compared to controls. CRSwNP had
      elevated mucus levels of IL-4, 6, 10, 17A, and TNF-alpha compared to controls.
      CONCLUSIONS: Cytokine levels in sinus secretions correlate with levels in sinus
      tissue and are elevated in CRS versus control based on Th1/Th2 skewing.

PMID- 23852963
TI  - Determinants of cough efficiency in Duchenne muscular dystrophy.
AB  - OBJECTIVE: With the progression of Duchenne muscular dystrophy (DMD) cough
      becomes inefficient leading to recurrent chest infections. Several factors
      determine the effectiveness of cough in DMD patients. The aim of this study was
      to investigate how weakened inspiratory muscles alter operating lung and thoraco
      abdominal volumes and whether they contribute to cough efficiency. PATIENTS AND
      METHODS: Pulmonary function, respiratory muscle strength, and peak cough flow
      (PCF) were assessed in 36 DMD patients (age 17.0 +/- 5.0). Total and
      compartmental chest wall volumes were measured by Opto-Electronic Plethysmography
      in the DMD patients and 15 age-matched controls during quiet breathing and
      maximal voluntary cough maneuvers. The DMD population was divided into three
      groups: PCF < 160 L/min (inefficient cough), PCF > 270 L/min (efficient cough),
      and 160 < PCF < 270 L/min (intermediate cough efficiency). RESULTS: During the
      inspiration preceding cough, patients with efficient cough presented normal
      volume variations whereas patients with intermediate cough efficiency showed low
      abdominal volume variation (P < 0.01). Patients with inefficient cough were
      characterized by reduced total (P < 0.05) and compartmental (ribcage: P < 0.01;
      abdomen: P < 0.001) chest wall volumes during the inspiration preceding cough and
      reduced abdominal contribution to tidal volume during quiet breathing (DeltaVAB
      (%VT), P < 0.001). ROC analysis revealed that among all spirometric, respiratory
      muscle strength and chest wall parameters DeltaVAB (%VT ) was the best
      discriminator between inefficient and efficient cough. CONCLUSIONS: Inefficient
      cough in DMD is associated to reduced operating lung and chest wall volume
      secondary to weakened inspiratory muscles. Abdominal contribution to tidal volume
      during spontaneous breathing represents a non-volitional and noninvasive index
      able to discriminate efficient and inefficient cough.

PMID- 23852964
TI  - Dose-dependent surface endothelialization and biocompatibility of polyurethane
      noble metal nanocomposites.
AB  - Surface pre-endothelialization is a promising approach to improve the
      hemocompatibility of implants, medical devices, and artificial organs. To promote
      the adhesive property of thermoplastic polyurethane (TPU) for endothelial cells
      (ECs), up to 1 wt % of gold (Au) or platinum (Pt) nanoparticles, fabricated by
      pulsed laser ablation in polymer solution, were embedded into the polymer matrix.
      The analysis of these nanocomposites showed a homogenous dispersion of the
      nanoparticles, with average diameters of 7 nm for Au or 9 nm for Pt. A dose
      dependent effect was found when ECs were seeded onto nanocomposites comprising
      different nanoparticle concentrations, resulting in a fivefold improvement of
      proliferation at 0.1 wt % nanoparticle load. This effect was associated with a
      nanoparticle concentration-dependent hydrophilicity and negative charge of the
      nanocomposite. In dynamic flow tests, nanocomposites containing 0.1 wt % Au or Pt
      nanoparticles allowed for the generation of a confluent and resistant EC layer.
      Real-time polymerase chain reaction quantification of specific markers for EC
      activation indicated that ECs cultivated on nanocomposites remain in an
      inactivated, nonthrombogenic and noninflammatory state; however, maintain the
      ability to trigger an inflammatory response upon stimulation. These findings were
      confirmed by a platelet and leukocyte adhesion assay. The results of this study
      suggest the possible applicability of TPU nanocomposites, containing 0.1 wt % Au
      or Pt nanoparticles, for the generation of pre-endothelialized surfaces of
      medical devices.

PMID- 23852965
TI  - Slow magnetic relaxation in a Co(II)-Y(III) single-ion magnet with positive axial
      zero-field splitting.

PMID- 23852966
TI  - A piezo-powered floating-gate sensor array for long-term fatigue monitoring in
      biomechanical implants.
AB  - Measurement of the cumulative loading statistics experienced by an implant is
      essential for prediction of long-term fatigue failure. However, the total power
      that can be harvested using typical in-vivo strain levels is less than 1 muW. In
      this paper, we present a novel method for long-term, battery-less fatigue
      monitoring by integrating piezoelectric transduction with hot-electron injection
      on a floating-gate transistor array. Measured results from a fabricated prototype
      in a 0.5-mum CMOS process demonstrate that the array can sense, compute, and
      store loading statistics for over 70000 stress-strain cycles which can be
      extended to beyond 107 cycles. The measured response also shows excellent
      agreement with a theoretical model and the nominal power dissipation of the array
      has been measured to be less than 800 nW. 

PMID- 23852967
TI  - Low-power circuits for brain-machine interfaces.
AB  - This paper presents work on ultra-low-power circuits for brain-machine interfaces
      with applications for paralysis prosthetics, stroke, Parkinson's disease,
      epilepsy, prosthetics for the blind, and experimental neuroscience systems. The
      circuits include a micropower neural amplifier with adaptive power biasing for
      use in multi-electrode arrays; an analog linear decoding and learning
      architecture for data compression; low-power radio-frequency (RF) impedance
      modulation circuits for data telemetry that minimize power consumption of
      implanted systems in the body; a wireless link for efficient power transfer;
      mixed-signal system integration for efficiency, robustness, and programmability;
      and circuits for wireless stimulation of neurons with power-conserving sleep
      modes and awake modes. Experimental results from chips that have stimulated and
      recorded from neurons in the zebra finch brain and results from RF power-link, RF
      data-link, electrode-recording and electrode-stimulating systems are presented.
      Simulations of analog learning circuits that have successfully decoded
      prerecorded neural signals from a monkey brain are also presented. 

PMID- 23852968
TI  - Active High Power Conversion Efficiency Rectifier With Built-In Dual-Mode Back
      Telemetry in Standard CMOS Technology.
AB  - In this paper, we present an active rectifier with high power conversion
      efficiency (PCE) implemented in a 0.5- mum 5 V standard CMOS technology with two
      modes of built-in back telemetry; short- and open-circuit. As a rectifier, it
      ensures a PCE > 80%, taking advantage of active synchronous rectification
      technique in the frequency range of 0.125-1 MHz. The built-in complementary back
      telemetry feature can be utilized in implantable microelectronic devices (IMD),
      wireless sensors, and radio frequency identification (RFID) applications to
      reduce the silicon area, increase the data rate, and improve the reading range
      and robustness in load shift keying (LSK). 

PMID- 23852969
TI  - A Low-Light CMOS Contact Imager With an Emission Filter for Biosensing
      Applications.
AB  - In this paper, a fully functional low light 128 X 128 contact image sensor for
      cell detection in biosensing applications is presented. The imager, fabricated in
      0.18 mum CMOS technology, provides low-noise operation by employing both a
      modified version of the active reset (AR) technique and a modified version of the
      active column sensor (ACS) readout method. High-sensitivity, low noise
      performance of the presented sensor is well-suited for fluorescence imaging. For
      this purpose, an emission filter was fabricated and integrated with the sensor.
      The filter was fabricated using PDMS and Sudan II Blue dye mix, spin-coated and
      deposited in a class 1000 clean room. The designed filter is suitable for
      excitation at wavelengths below 340 nm and emission at 450 nm and above. The
      fabricated imager architecture and operation are described, noise analysis is
      presented and measurements from a test chip are shown. Experimental results using
      live neurons from the pond snail, Lymnaea stagnalis, and fluorescence polystyrene
      micro-beads prove the functionality of the fabricated system and indicate its
      biocompatiblity. 

PMID- 23852970
TI  - A silicon central pattern generator controls locomotion in vivo.
AB  - We present a neuromorphic silicon chip that emulates the activity of the
      biological spinal central pattern generator (CPG) and creates locomotor patterns
      to support walking. The chip implements ten integrate-and-fire silicon neurons
      and 190 programmable digital-to-analog converters that act as synapses. This
      architecture allows for each neuron to make synaptic connections to any of the
      other neurons as well as to any of eight external input signals and one tonic
      bias input. The chip's functionality is confirmed by a series of experiments in
      which it controls the motor output of a paralyzed animal in real-time and enables
      it to walk along a three-meter platform. The walking is controlled under closed
      loop conditions with the aide of sensory feedback that is recorded from the
      animal's legs and fed into the silicon CPG. Although we and others have
      previously described biomimetic silicon locomotor control systems for robots,
      this is the first demonstration of a neuromorphic device that can replace some
      functions of the central nervous system in vivo. 

PMID- 23852971
TI  - A 1.2-V 140-nW 10-bit Sigma-Delta Modulator for Electroencephalogram
      Applications.
AB  - This paper presents a second-order Sigma-Delta modulator for electroencephalogram
      applications with 10 bits of resolution, 1.2 V of supply voltage, and only 140 nW
      of power consumption over a bandwidth of 25 Hz. Low-voltage operation has been
      achieved using quasi-floating-gate-based circuits. The use of a new class-AB
      operational amplifier in weak inversion allows very low power consumption.
      Experimental results show an energy efficiency of 1.6 pJ per quantization level,
      making it the most energy-efficient converter reported to date in the very low
      signal bandwidth range. 

PMID- 23852972
TI  - An Integrated Implantable Stimulator That is Fail-Safe Without Off-Chip Blocking
      Capacitors.
AB  - We present a neural stimulator chip with an output stage (electrode driving
      circuit) that is fail-safe under single-fault conditions without the need for off
      chip blocking-capacitors. To miniaturize the stimulator output stage two novel
      techniques are introduced. The first technique is a new current generator circuit
      reducing to a single step the translation of the digital input bits into the
      stimulus current, thus minimizing silicon area and power consumption compared to
      previous works. The current generator uses voltage-controlled resistors
      implemented by MOS transistors in the deep triode region. The second technique is
      a new stimulator output stage circuit with blocking-capacitor safety protection
      using a high-frequency current-switching (HFCS) technique. Unlike conventional
      stimulator output stage circuits for implantable functional electrical
      stimulation (FES) systems which require blocking-capacitors in the microfarad
      range, our proposed approach allows capacitance reduction to the picofarad range,
      thus the blocking-capacitors can be integrated on-chip. The prototype four
      channel neural stimulator chip was fabricated in XFAB's 1-mum silicon-on
      insulator CMOS technology and can operate from a power supply between 5-18 V. The
      stimulus current is generated by active charging and passive discharging. We
      obtained recordings of action potentials and a strength-duration curve from the
      sciatic nerve of a frog with the stimulator chip which demonstrate the HFCS
      technique. The average power consumption for a typical 1-mA 20-Hz single-channel
      stimulation using a book electrode, is 200 muW from a 6 V power supply. The
      silicon area occupation is 0.38 mm(2) per channel. 

PMID- 23852974
TI  - A low-power programmable neural spike detection channel with embedded calibration
      and data compression.
AB  - This paper reports a programmable 400 MUm pitch neural spike recording channel,
      fabricated in a 130 nm standard CMOS technology, which implements amplification,
      filtering, digitization, analog spike detection plus feature extraction, and self
      calibration functionalities. It can operate in two different output modes: 1)
      signal tracking, in which the neural signal is sampled and transmitted as raw
      data; and 2) feature extraction, in which the spikes of the neural signal are
      detected and encoded by piece-wise linear curves. Additionally, the channel
      offers a foreground calibration procedure in which the amplification gain and the
      passband of the embedded filter can be self-adjusted. The amplification stage
      obtains a noise efficiency factor of 2.16 and an input referred noise of 2.84
      MUVrms over a nominal bandwidth of 167 Hz-6.9 kHz. The channel includes a
      reconfigurable 8-bit analog-to-digital converter combined with a 3-bit controlled
      programmable gain amplifier for adjusting the input signal to the full scale
      range of the converter. This combined block achieves an overall energy
      consumption per conversion of 102 fJ at 90 kS/s. The energy consumed by the
      circuit elements which are strictly related to the digitization process is 14.12
      fJ at the same conversion rate. The complete channel consumes 2.8 MUW at 1.2 V
      voltage supply when operated in the signal tracking mode, and 3.1 MUW when the
      feature extraction mode is enabled. 

PMID- 23852975
TI  - A multichannel integrated circuit for electrical recording of neural activity,
      with independent channel programmability.
AB  - Since a few decades, micro-fabricated neural probes are being used, together with
      microelectronic interfaces, to get more insight in the activity of neuronal
      networks. The need for higher temporal and spatial recording resolutions imposes
      new challenges on the design of integrated neural interfaces with respect to
      power consumption, data handling and versatility. In this paper, we present an
      integrated acquisition system for in vitro and in vivo recording of neural
      activity. The ASIC consists of 16 low-noise, fully-differential input channels
      with independent programmability of its amplification (from 100 to 6000 V/V) and
      filtering (1-6000 Hz range) capabilities. Each channel is AC-coupled and
      implements a fourth-order band-pass filter in order to steeply attenuate out-of
      band noise and DC input offsets. The system achieves an input-referred noise
      density of 37 nV/?Hz, a NEF of 5.1, a CMRR > 60 dB, a THD < 1% and a sampling
      rate of 30 kS/s per channel, while consuming a maximum of 70 MUA per channel from
      a single 3.3 V. The ASIC was implemented in a 0.35 MUm CMOS technology and has a
      total area of 5.6 * 4.5 mm2. The recording system was successfully validated in
      in vitro and in vivo experiments, achieving simultaneous multichannel recordings
      of cell activity with satisfactory signal-to-noise ratios.

PMID- 23852976
TI  - CMOS low current measurement system for biomedical applications.
AB  - We present a micro-chip implementation of a low current measurement system for
      biomedical applications using capacitive feedback that exhibits 190 fA of RMS
      noise in a 1 kHz bandwidth. The sampling rate is selectable up to 100 kHz. When
      measuring the amplifier noise with a 10 GOmega resistor and a 47 pF capacitor at
      the input, typical of cell membrane capacitance in DNA and patch clamp
      experiments, the measured RMS noise was 2.44 pA on a 50 pA signal in a 10 kHz
      bandwidth. Two channels were implemented on 630 * 440 MUm2 using a 0.5-MUm 3
      metal 2-poly CMOS process. Each channel consumes 1.5 mW of power from a 3.3 V
      supply. We measured the characteristics of an artificial lipid bilayer similar to
      the ones used in DNA sequencing experiments via nanopores.

PMID- 23852973
TI  - Use of health information technology to reduce diagnostic errors.
AB  - BACKGROUND: Health information technology (HIT) systems have the potential to
      reduce delayed, missed or incorrect diagnoses. We describe and classify the
      current state of diagnostic HIT and identify future research directions. METHODS:
      A multi-pronged literature search was conducted using PubMed, Web of Science,
      backwards and forwards reference searches and contributions from domain experts.
      We included HIT systems evaluated in clinical and experimental settings as well
      as previous reviews, and excluded radiology computer-aided diagnosis, monitor
      alerts and alarms, and studies focused on disease staging and prognosis. Articles
      were organised within a conceptual framework of the diagnostic process and areas
      requiring further investigation were identified. RESULTS: HIT approaches, tools
      and algorithms were identified and organised into 10 categories related to those
      assisting: (1) information gathering; (2) information organisation and display;
      (3) differential diagnosis generation; (4) weighing of diagnoses; (5) generation
      of diagnostic plan; (6) access to diagnostic reference information; (7)
      facilitating follow-up; (8) screening for early detection in asymptomatic
      patients; (9) collaborative diagnosis; and (10) facilitating diagnostic feedback
      to clinicians. We found many studies characterising potential interventions, but
      relatively few evaluating the interventions in actual clinical settings and even
      fewer demonstrating clinical impact. CONCLUSIONS: Diagnostic HIT research is
      still in its early stages with few demonstrations of measurable clinical impact.
      Future efforts need to focus on: (1) improving methods and criteria for
      measurement of the diagnostic process using electronic data; (2) better usability
      and interfaces in electronic health records; (3) more meaningful incorporation of
      evidence-based diagnostic protocols within clinical workflows; and (4) systematic
      feedback of diagnostic performance.

PMID- 23852977
TI  - Dielectrophoresis-based integrated Lab-on-Chip for nano and micro-particles
      manipulation and capacitive detection.
AB  - We present in this paper a new Lab-on-Chip (LoC) architecture for
      dielectrophoresis-based cell manipulation, detection, and capacitive measurement.
      The proposed LoC is built around a CMOS full-custom chip and a microfluidic
      structure. The CMOS chip is used to deliver all parameters required to control
      the dielectrophoresis (DEP) features such as frequency, phase, and amplitude of
      signals spread on in-channel electrodes of the LoC. It is integrated to the LoC
      and experimental results are related to micro and nano particles manipulation and
      detection in a microfluidic platform. The proposed microsystem includes an on
      chip 27-bit frequency divider, a digital phase controller with a 3.6 degrees 
      phase shift resolution and a 2.5 V dynamic range. The sensing module is composed
      of a 3 * 3 capacitive sensor array with 10 fF per mV sensitivity, and a dynamic
      range of 1.5 V. The obtained results show an efficient nano and micro-particles
      (PC05N, PA04N and PS03N) separation based on frequency segregation with low
      voltages less than 1.7 V and a fully integrated and reconfigurable system.

PMID- 23852978
TI  - Parameter estimation of a spiking silicon neuron.
AB  - Spiking neuron models are used in a multitude of tasks ranging from understanding
      neural behavior at its most basic level to neuroprosthetics. Parameter estimation
      of a single neuron model, such that the model's output matches that of a
      biological neuron is an extremely important task. Hand tuning of parameters to
      obtain such behaviors is a difficult and time consuming process. This is further
      complicated when the neuron is instantiated in silicon (an attractive medium in
      which to implement these models) as fabrication imperfections make the task of
      parameter configuration more complex. In this paper we show two methods to
      automate the configuration of a silicon (hardware) neuron's parameters. First, we
      show how a Maximum Likelihood method can be applied to a leaky integrate and fire
      silicon neuron with spike induced currents to fit the neuron's output to desired
      spike times. We then show how a distance based method which approximates the
      negative log likelihood of the lognormal distribution can also be used to tune
      the neuron's parameters. We conclude that the distance based method is better
      suited for parameter configuration of silicon neurons due to its superior
      optimization speed. 

PMID- 23852979
TI  - Spiking neuron computation with the time machine.
AB  - The Time Machine (TM) is a spike-based computation architecture that represents
      synaptic weights in time. This choice of weight representation allows the use of
      virtual synapses, providing an excellent tradeoff in terms of flexibility,
      arbitrary weight connections and hardware usage compared to dedicated synapse
      architectures. The TM supports an arbitrary number of synapses and is limited
      only by the number of simultaneously active synapses to each neuron. SpikeSim, a
      behavioral hardware simulator for the architecture, is described along with
      example algorithms for edge detection and objection recognition. The TM can
      implement traditional spike-based processing as well as recently developed time
      mode operations where step functions serve as the input and output of each neuron
      block. A custom hybrid digital/analog implementation and a fully digital
      realization of the TM are discussed. An analog chip with 32 neurons, 1024
      synapses and an address event representation (AER) block has been fabricated in
      0.5 MUm technology. A fully digital field-programmable gate array (FPGA)-based
      implementation of the architecture has 6,144 neurons and 100,352 simultaneously
      active synapses. Both implementations utilize a digital controller for routing
      spikes that can process up to 34 million synapses per second. 

PMID- 23852980
TI  - Compressed sensing system considerations for ECG and EMG wireless biosensors.
AB  - Compressed sensing (CS) is an emerging signal processing paradigm that enables
      sub-Nyquist processing of sparse signals such as electrocardiogram (ECG) and
      electromyogram (EMG) biosignals. Consequently, it can be applied to biosignal
      acquisition systems to reduce the data rate to realize ultra-low-power
      performance. CS is compared to conventional and adaptive sampling techniques and
      several system-level design considerations are presented for CS acquisition
      systems including sparsity and compression limits, thresholding techniques,
      encoder bit-precision requirements, and signal recovery algorithms. Simulation
      studies show that compression factors greater than 16X are achievable for ECG and
      EMG signals with signal-to-quantization noise ratios greater than 60 dB. 

PMID- 23852981
TI  - Energy-efficient context classification with dynamic sensor control.
AB  - Energy efficiency has been a longstanding design challenge for wearable sensor
      systems. It is especially crucial in continuous subject state monitoring due to
      the ongoing need for compact sizes and better sensors. This paper presents an
      energy-efficient classification algorithm, based on partially observable Markov
      decision process (POMDP). In every time step, POMDP dynamically selects sensors
      for classification via a sensor selection policy. The sensor selection problem is
      formalized as an optimization problem, where the objective is to minimize
      misclassification cost given some energy budget. State transitions are modeled as
      a hidden Markov model (HMM), and the corresponding sensor selection policy is
      represented using a finite-state controller (FSC). To evaluate this framework,
      sensor data were collected from multiple subjects in their free-living
      conditions. Relative accuracies and energy reductions from the proposed method
      are compared against naive Bayes (always-on) and simple random strategies to
      validate the relative performance of the algorithm. When the objective is to
      maintain the same classification accuracy, significant energy reduction is
      achieved. 

PMID- 23852982
TI  - Design and integration of a high accuracy multichannel analog CMOS peak detect
      and hold circuit for APD-based PET imaging.
AB  - This paper presents the design of a high accuracy multichannel peak detect and
      hold (PDH) circuit. This PDH measures the energy of an event and is one part of a
      readout chain for avalanche photo diodes (APD)-based positron emission tomography
      (PET) imaging. The circuit is designed in a 0.35MUm CMOS process. The proposed
      PDH is dedicated to ultra low amplitude, large amplitude range from several tens
      millivolts to 1.1 V, and fast peaking time (190 ns) semi-Gaussian pulses. The two
      phase technique has been used to cancel the major error source of the classical
      CMOS PDH: offset. A two-gain OTA is applied to minimize the DC error. A peak
      error less 1% for a small input signal (amplitude is between 40 mV and 300 mV)
      and a peak error less than 0.2% for a large input signal (amplitude is between
      300 mV and 1.1 V) have been obtained from test. The area of a PDH is equal to
      about 200 MUm * 40 MUm. In our PDH system, the drop rate is negligible. 

PMID- 23852983
TI  - Characterization of secretagogin-immunoreactive amacrine cells in marmoset
      retina.
AB  - The retina contains at least 30 different types of amacrine cells but not many
      are well characterized. In the present study the calcium-binding protein
      secretagogin was localized in a population of regular and displaced amacrine
      cells in the retina of the common marmoset Callithrix jacchus. Irrespective of
      their soma location, the dendrites of secretagogin amacrine cells occupy strata
      2, 3, and 4 of the inner plexiform layer, between the two bands formed by
      cholinergic amacrine cells. Segretagogin amacrine cells are also immunopositive
      to antibodies against glutamic acid decarboxylase, suggesting that they use gamma
      aminobutyric acid (GABA) as their neurotransmitter. The spatial density of
      secretagogin amacrine cells decreases from a peak of about 400 cells/mm(2) near 1
      mm eccentricity to less than 100 cells/mm(2) in peripheral retina; these
      densities account for about 1% of amacrine cells in the inner nuclear layer and
      for up to 27% of displaced amacrine cells. The cell bodies form a regular mosaic,
      suggesting that they constitute a single amacrine cell population. Secretagogin
      cells have varicose dendrites, which are decorated with small spines.
      Intracellular injection of DiI into secretagogin cells revealed an average
      dendritic field diameter of 170 MUm and an average coverage factor of 3.2. In
      summary, secretagogin cells in marmoset retina are medium-field amacrine cells
      that share their stratification pattern with narrow-field amacrine cells and
      their neurotransmitter with wide-field amacrine cells. They may mediate spatial
      inhibition spanning the centralmost (on and off) bands of the inner plexiform
      layer.

PMID- 23852984
TI  - Liberalising trade in health services: constraints and prospects for South Asian
      countries.
AB  - This paper attempts to examine the prospects and challenges associated with
      liberalising trade in health services in five South Asian countries, namely
      Bangladesh, India, Nepal, Pakistan and Sri Lanka. Country-specific secondary
      information, a brief literature review of empirical studies and debriefing
      sessions with key stakeholders are employed to explore the issues related to
      liberalising health services trade. The health sectors in India, Nepal and
      Pakistan are scheduled under General Agreement on Trade in Services (GATS)
      classification, whereas those in Bangladesh and Sri Lanka are not. In Bangladesh,
      there is opportunity for investment in joint venture hospitals under Mode 3.
      Nonetheless, India is the largest trader in health services under all four modes.
      In Sri Lanka, cross-border trade in healthcare services is found to be
      insignificant. Moreover, expertise in eye treatment in Nepal could also attract
      foreign investment in medical services under Mode 3. In contrast, Pakistan
      exhibits no potential under Mode 4, because of a lack of healthcare
      professionals. In this view, the prospects of trade in health services within the
      South Asian region under the four GATS modes are constrained by infrastructural,
      regulatory, perception-related, logistical and cultural problems. Considering the
      level of development and commercial opportunities, regional integration in the
      health sector could be explored in such areas as telemedicine, medical tourism,
      cross-border investment and capacity building of health personnel. These
      developments call for stronger and pro-active government-to-government
      collaboration in the South Asian Association of Regional Cooperation (SAARC)
      region in a transparent and accountable manner.

PMID- 23852985
TI  - The trade-off between costs and quality of care in the treatment of psychosomatic
      patients with somatoform pain disorder.
AB  - BACKGROUND: The introduction of efficiency-oriented provider payment systems in
      inpatient mental healthcare in various Western countries may lead to the use of
      less healthcare resources in the treatment of patients. To avoid unintended
      effects on quality of care that may result from reductions in resource
      utilization, it is essential for decision and policy makers to know whether there
      is a trade-off between costs and quality of care. AIM OF THE STUDY: The aim of
      this study was to investigate and quantify the relationship between costs and
      outcomes in psychosomatic inpatients with somatoform pain disorder. METHODS: The
      inclusion criteria for patient selection (n = 101) were (i) a main diagnosis of
      somatoform pain disorder according to International Classification of Diseases-10
      (ICD-10) [F45.4, F45.40, F45.41]; (ii) complete data on the mental component
      summary reflecting overall functioning of mental health (MCS-8) measured with the
      Short Form-8 Health Survey (SF-8) within 3 days of the admission and discharge
      dates; and (iii) treatment at Charite Universitaetsmedizin (Berlin, Germany)
      during the period January 2006-June 2010. The change in the MCS-8 score incurred
      over the treatment period was used as an indicator of quality of care. Treatment
      costs were calculated from the provider's perspective, mainly using bottom-up
      micro-costing. The year of valuation for cost calculation was 2008 (with no
      inflation adjustment); for costs provided by the accounting department for
      services consumed by the patient, the valuation year was based on the year of
      service provision. We hypothesized that the outcome 'change in MCS-8 score' was a
      function of the independent variable costs, patient characteristics, socio
      demographic variables, pain-related variables, co-morbidities and subjective
      illness attribution, i.e. whether patients attributed the origin of pain mainly
      to a somatic cause or not. An interaction term between costs and illness
      attribution was included to control for the hypothesized differing effects of
      resource input or costs on the outcome variable conditional on patients' illness
      attribution. Hausman tests indicated that endogeneity was not present, thus,
      ordinary least squares regression (OLS) was conducted. We assessed whether the
      change in the MCS-8 score was clinically meaningful and perceptible by the
      patient, using the minimal clinical important difference (MCID). For Short Form
      Health Surveys, the MCID for changes in the mental component summary is typically
      around 3 points. RESULTS: We found a trade-off between costs and outcome for
      patients without or with only minor somatic illness attribution (77 % of the
      sample). This patient group improved 0.4 points in outcome after every 100 <euro>
      increase in total costs per case (F 1,77 = 13.836, t(77) = 3.72, p = 0.0004). For
      patients with mainly somatic illness beliefs (23 % of the sample), we did not
      find a trade-off between costs and outcome. CONCLUSION: For the majority of
      patients, we found a trade-off between costs and health outcome, thus, it seems
      advisable to carefully monitor outcome parameters when applying cost containment
      measures.

PMID- 23852987
TI  - Yeast-expressed bacteriophage-like particles for the packaging of nanomaterials.
AB  - Virus-like particles (VLPs) generated by heterologous expression of viral
      structural genes have become powerful tools in vaccine development. Recently, we
      and others have reported on the assembly of VLPs of the RNA bacteriophages MS2,
      Qbeta, and GA in yeast. Here, we investigate the formation of VLPs of five
      additional phages in the yeasts Saccharomyces cerevisiae and Pichia pastoris,
      namely, the coliphages SP and fr, Acinetobacter phage AP205, Pseudomonas phage
      PP7, and Caulobacter phage phiCb5. In all cases except SP, particle formation was
      detected, although VLP outcome varied from 0.2 to 8 mg from 1 g of wet cells. We
      have found that phage phiCb5 VLPs easily dissociate into coat protein dimers when
      applied to strong anion exchangers. Upon salt removal and the addition of nucleic
      acid or its mimics and calcium ions, the dimers re-assemble into VLPs with high
      efficiency. A variety of compounds, including RNA, DNA, and gold nanoparticles
      can be packaged inside phiCb5 VLPs. The ease with which phage phiCb5 coat protein
      dimers can be purified in high quantities and re-assembled into VLPs makes them
      attractive for downstream applications including the internal packaging of
      nanomaterials and the chemical coupling of peptides of interest on the surface. 

PMID- 23852986
TI  - Protein production in Yarrowia lipolytica via fusion to the secreted lipase
      Lip2p.
AB  - We established a strategy for protein production and purification via expression
      in Yarrowia lipolytica as Lip2p fusion protein. To evaluate the expression system
      a cysteine-rich miniprotein, an antibody fragment and an enzyme showing galactose
      oxidase activity were chosen. These proteins have varying disulfide bond content,
      size, and structural complexity. Endogenous lipase Lip2p was used as a fusion
      partner to direct the fused proteins to the extracellular medium. A linker
      sequence was introduced at the junction of Lip2p and the respective fused protein
      that contains a hexahistidine tag followed by a TEV protease cleavage site. This
      allows for a specific and simple purification via IMAC for capturing the secreted
      proteins from the supernatant followed by a second IMAC for removing all
      contaminants after proteolytic release of the protein of interest. Up to 174 mg/L
      fusion protein was obtained using shake flask cultivation. Functionality of each
      of the purified proteins was confirmed by individual assays. Expression of
      proteins of interest via Lip2p fusion not only provides a convenient expression
      and purification scheme but also enables for an online monitoring of accumulation
      of secreted fusion proteins in the medium by exploiting the intrinsic lipase
      activity of the fusion.

PMID- 23852988
TI  - On the potential of hydrated storage for naturally derived ECMs and associated
      effects on mechanical and cellular performance.
AB  - Tissue engineered acellular vascular grafts are an emerging concept in the
      development of vascular prostheses for the minimally invasive treatment of
      cardiovascular diseases. Extracellular matrix (ECM) scaffolds, such as small
      intestinal submucosa (SIS) and urinary bladder matrix (UBM), offer many
      advantages over currently available synthetic devices. However, storage of such
      biomaterials can unduly influence the scaffold properties. This study evaluated
      the effects of up to 16 weeks hydrated storage on the mechanical and cellular
      performance of stented and unstented tubular scaffolds. This study aimed to
      demonstrate the viability, mechanical integrity, and bioactive potential of
      xenogeneic ECMs as potential off-the-shelf vascular prosthetic devices.
      Rehydrated ECM samples versus the lyophilized controls showed an increase in UTS
      and stiffness. The mechanical strength of all samples evaluated was above the
      average reported aortic tissue failure strength and more compliant than current
      synthetic materials employed. Post-storage cellular bioactivity investigations
      indicated that both ECM scaffolds tested were unaffected by increased hydrated
      storage duration when compared with the controls. Overall, the results indicate
      that the biomechanical and biologic properties of ECMs are not negatively
      affected by long-term hydrated storage. Therefore, with further investigations,
      naturally derived ECM materials may offer potential as an off-the-shelf
      therapeutic treatment of cardiovascular diseases.

PMID- 23852989
TI  - Muscle architecture adaptations to knee extensor eccentric training: rectus
      femoris vs. vastus lateralis.
AB  - INTRODUCTION: Changes in muscle architecture induced by eccentric knee extensor
      training remain unclear, as well the adaptive responses of synergistic knee
      extensor muscles with different geometrical designs. METHODS: Ultrasonography
      images were taken from rectus femoris (RF) and vastus lateralis (VL) of 20 male
      volunteers before and after a non-training control period of 4 weeks, and
      additional evaluations were performed after 4, 8, and 12 weeks of isokinetic
      eccentric training. RESULTS: RF and VL had significant changes in muscle
      architecture within the first 4 training weeks, and the adaptive response
      throughout the intervention was similar. Muscle thickness increased by around 7
      10%, fascicle length increased 17-19%, and pennation angle was unchanged.
      CONCLUSIONS: Increased muscle thickness due to eccentric training was related to
      increased fascicle length and not to pennation angle changes. Although RF and VL
      have a different fascicular geometry, they had similar morphological adaptations
      to eccentric training.

PMID- 23852990
TI  - What is the best practice for acute mastoiditis in children?

PMID- 23852991
TI  - Bacterial methanogenesis proceeds by a radical mechanism.

PMID- 23852992
TI  - Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is an inherited condition resulting in thickened,
      sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary
      infection and inflammation, is the most common cause of mortality. Muco-active
      therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum
      viscosity, increase airway clearance of sputum, reduce infection and inflammation
      and improve lung function. Thiol derivatives, either oral or nebulized, have
      shown benefit in other respiratory diseases. Their mode of action is likely to
      differ according to the route of administration. There are several thiol
      derivatives, and it is unclear which of these may be beneficial in cystic
      fibrosis. OBJECTIVES: To evaluate the efficacy and safety of nebulized and oral
      thiol derivatives in people with cystic fibrosis. SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising
      references identified from comprehensive electronic database searches, hand
      searches of relevant journals, abstract books and conference proceedings.Most
      recent search: 13 June 2013.We also conducted a PubMed search on 26 February 2013
      for relevant published articles. SELECTION CRITERIA: Randomized and quasi
      randomized controlled trials comparing nebulized or oral thiol derivatives to
      placebo or another thiol derivative in people with cystic fibrosis. DATA
      COLLECTION AND ANALYSIS: The authors independently assessed trials for inclusion,
      analysed risk of bias and extracted data. MAIN RESULTS: Searches identified 23
      trials; nine trials (255 participants) are included, of these seven trials are
      more than 10 years old. Three trials of nebulized thiol derivatives were
      identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another
      compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another
      compared glutathione to 4% hypertonic saline). Although generally well-tolerated
      with no significant adverse effects, there was no evidence of significant
      clinical benefit in our primary outcomes in participants receiving these
      treatments.Six trials of oral thiol derivatives were identified. Three trials
      compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and
      placebo; one compared carbocysteine to ambroxol; and one compared low and high
      dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with
      no significant adverse effects, however there was no evidence of significant
      clinical benefit in our primary outcomes in participants receiving these
      treatments. AUTHORS' CONCLUSIONS: We found no evidence to recommend the use of
      either nebulized or oral thiol derivatives in people with cystic fibrosis. There
      are very few good quality trials investigating the effect of these medications in
      cystic fibrosis, and further research is required to investigate the potential
      role of these medications in improving the outcomes of people with cystic
      fibrosis.

PMID- 23852993
TI  - Identification of the metabolites of anti-inflammatory compound
      clematichinenoside AR in rat intestinal microflora.
AB  - Clematichinenoside AR (C-AR), a pentacyclic triterpenoid saponin with anti
      inflammatory and anti-rheumatoid activities, is the main active component of the
      traditional Chinese medicine Clematidis Radix et Rhizoma. However, its poor oral
      absorption indicated that not only the parent compound C-AR itself, but also its
      metabolites could be responsible for the pharmacological effects in rats. The
      present study aimed to investigate the metabolism of C-AR in rat intestinal
      microflora, where C-AR was extensively metabolized. C-AR was incubated with the
      content of the large intestine. The culture solution was collected at different
      time points and analyzed for the metabolites of C-AR. Eight metabolites were
      identified by liquid chromatography/quadrupole time-of-flight mass spectrometry.
      M1, M2 and M5 were the major metabolites. In addition, it was proposed that
      deglycosylation was the only pathway contributing to the biotransformation of C
      AR in rat intestinal microflora.

PMID- 23852994
TI  - Conformational isomerism in monomeric, low-coordinate group 12 complexes
      stabilized by a naphthyl-substituted m-terphenyl ligand.
AB  - The synthesis and characterization of the first series of low-coordinate
      bis(terphenyl) complexes of the Group 12 metals, [Zn(2,6-Naph2 C6 H3 )2 ] (1),
      [Cd(OEt2 )(2,6-Naph2 C6 H3 )2 ] (2) and [Hg(OEt2 )(2,6-Naph2 C6 H3 )2 ] (3)
      (Naph=1-C10 H7 ) are described. The naphthyl substituents of the terphenyl
      ligands confer considerable steric bulk, and as a result of limited flexibility
      introduce multiple conformations to these unusual systems. In the solid state,
      complex 1 features a two-coordinate Zn centre with the ligands oriented in a
      syn/anti conformation, whereas the three-coordinate distorted T-shaped complexes
      2 and 3 feature the ligands in the syn/syn configurations. The results of DFT
      calculations are in good agreement with the solid-state configurations for these
      complexes and support the spectroscopic measurements, which indicate several
      conformers in solution. 

PMID- 23852995
TI  - Ruthenium carbenes supported on mesoporous silicas as highly active and selective
      hybrid catalysts for olefin metathesis reactions under continuous flow.
AB  - In the search for a highly active and selective heterogenized metathesis
      catalyst, we systematically varied the pore geometry and size of various silica
      based mesoporous (i.e., MCM-41, MCM-48, and SBA-15) and microporous (ZSM-5 and
      MWW) versus macroporous materials (D11-10 and Aerosil 200), besides other process
      parameters (temperature, dilution, and mean residence time). The activity and,
      especially, selectivity of such "linker-free" supports for ruthenium metathesis
      catalysts were evaluated in the cyclodimerization of cis-cyclooctene to form 1,9
      cyclohexadecadiene, a valuable intermediate in the flavor and fragrance industry.
      The optimized material showed not only exceptionally high selectivity to the
      valuable product, but also turned out to be a truly heterogeneous catalyst with
      superior activity relative to the unsupported homogeneous complex. 

PMID- 23852996
TI  - Modulation of physical environment makes placental mesenchymal stromal cells
      suitable for therapy.
AB  - Low level of oxygen at the site of injury is likely to affect the viability and
      proliferation of the transplanted mesenchymal stromal cells (MSCs). Hence there
      is a need to understand the effect of the physical environment on transplanted
      stromal cells. Therefore, we have studied the effect of the duration of hypoxic
      exposure alone or in combination with normoxia on placenta derived mesenchymal
      stem cell (PDMSCs). PDMSCs and bone marrow MSCs (BMMSCs) were analysed under four
      different culture conditions, exposure to direct normoxia (N), direct hypoxia (H)
      and intermittent normoxia followed by hypoxia (NH) and intermittent hypoxia
      followed by normoxia (HN). The effect on morphology, proliferation, metabolic
      activity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide)
      and viability by 7AAD (7-amino-actinomycin D) were assayed, along with markers
      for MSCs and HLADR. No change in morphology, marker expression or HLADR was
      detected in N, H, NH or HN. An increase in proliferation rate, decrease in
      population doubling-time (PDT) and a relative increase in metabolic activity was
      strongly noted in the order: NH, N/HN and H. No significant difference was
      observed in the viability between N, H, NH or HN. A similar pattern was also
      observed in BMMSCS, indicating comparable suitability of PDMSCs in therapeutic
      applications. Thus we conclude that intermittent exposure to normoxia prior to
      hypoxic exposure is a better option than direct exposure to hypoxia. This may
      have clinical relevance in that they probably mirror the in vivo scenario of
      systemic delivery (NH) of cells as opposed to local delivery (H), thereby
      suggesting that systemic delivery is better than local delivery. 

PMID- 23852997
TI  - Diagnosis and acute management of patients with concussion at children's
      hospitals.
AB  - OBJECTIVES: To describe the number of hospital admissions for concussion at
      paediatric hospitals in the USA. To describe the use of imaging and medications
      for acute concussion paediatric patients. DESIGN: Cross-sectional study. SETTING:
      Children's hospitals participating in the Pediatric Health Information System in
      the USA during a 10-year period. PATIENTS: All emergency department (ED) visits
      and inpatient admissions with the primary diagnosis of concussion, defined as
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes for: (1) concussion, (2) postconcussion syndrome or (3) skull fracture
      without mention of intracranial injury with concussion. MAIN OUTCOME MEASURES:
      The proportion of concussion patients who were hospitalised, underwent imaging or
      received medication, and the adjusted costs of visits for concussion. RESULTS:
      The number of ED visits for concussion increased between 2001 and 2010 (2126
      (0.36% of all ED visits) vs 4967 (0.62% of all ED visits); p<0.001), while the
      number of admissions remained stable. Of ED visits for concussion, 59.9% received
      CT and 47.7% received medications or intravenous fluids. Non-narcotic analgesics
      were the most common medication administered. Adjusted costs of patient visits
      were significantly higher when imaging was obtained (US$695, IQR US$472-$1009, vs
      US$191, IQR US$114-$287). An ED visit with CT, however, cost less than a
      hospitalisation without CT (US$1907, IQR US$1292-$3770). CONCLUSIONS: Although
      the number of ED patients diagnosed with concussion has increased, the number
      admitted has remained stable. Concussion patients at paediatric hospitals in the
      USA commonly undergo CT imaging and receive medication.

PMID- 23852999
TI  - Rational prescribing is important in all settings.

PMID- 23852998
TI  - Screening of selected risk factors in developmental dysplasia of the hip: an
      observational study.
AB  - BACKGROUND: Developmental dysplasia of the hip (DDH) is the most common neonatal
      musculoskeletal condition. In 2008, the NHS Newborn and Infant Physical
      Examination committee added selective 'at risk' screening to the existing
      universal neonatal and general practitioner clinical hip screening guidelines.
      OBJECTIVE: Assessment of breech and family history risk factors in DDH. DESIGN: A
      15 year prospective, observational, longitudinal cohort study. METHOD: Breech
      presentation and evidence of a strong family history for DDH were the 'risk
      factors' studied. All infants referred were clinically and sonographically
      screened by one consultant paediatric orthopaedic surgeon. RESULTS: From a cohort
      of 64 670 live births, 2984 neonates/infants, 46.1 (95% CI 44.6 to 47.8) per 1000
      live births, were referred and sonographically screened with these risk factors
      alone. 1360 were male, of which four were identified as having 'pathological' DDH
      (an incidence of 0.003 (95% CI 0.001 to 0.008)). 1624 were female, of which 45
      were identified as having 'pathological' DDH (an incidence of 0.028 (95% CI 0.021
      to 0.037)). This difference in incidence of 0.025 (95% CI 0.016 to 0.033) was
      statistically significant (p<0.001). From those who were clinically stable and
      screened with either or both of the two risk factors, four individuals were
      diagnosed with irreducible hip dislocation (0.06 (95% CI 0.024 to 0.159) per 1000
      live births). All were females. CONCLUSIONS: This study questions the current UK
      screening policy for DDH in clinically stable males referred with risk factors,
      and may influence future DDH screening programme policy.

PMID- 23853000
TI  - Long-term seroprotection after an adolescent booster meningococcal serogroup C
      vaccination.
AB  - OBJECTIVES: To determine long-term seroprotection after serogroup C meningococcal
      (MenC) vaccination at the age of 9-12 years, with or without booster vaccination
      at the age of 13-15 years. DESIGN: Observational cohort study; follow-on from
      randomised study. SETTING: Participants were recruited from English secondary
      schools (in Oxfordshire and Buckinghamshire). PARTICIPANTS AND INTERVENTIONS:
      Participants were primed with MenC CRM-glycoconjugate vaccine at the age of 9-12
      years in the UK routine immunisation campaign. In previous studies they were
      randomised at 13 to 15 years of age to receive a booster dose of MenC-CRM
      glycoconjugate vaccine (CRM-group) or bivalent meningococcal serogroup A/C
      polysaccharide vaccine (PS-group), or they received no additional doses of MenC
      vaccine (control group). In this follow-on study, a blood sample was obtained 11
      years after primary immunisation. Of 531 individuals eligible to participate, 134
      were enrolled, and 124 were included in the analysis. MAIN OUTCOME MEASURES: MenC
      serum bactericidal antibody (SBA) geometric mean titre; proportion of
      participants with SBA titre >=8 (putative protective threshold). RESULTS: Median
      ages at priming, boosting and blood sampling were 10.61, 14.42 and 22.11 years,
      respectively. Geometric mean titres for MenC SBA were: CRM group 1373 (95% CI 954
      to 1977); PS group 1024 (687 to 1526); and controls 284 (167 to 483). SBA titres
      >=8 were present in 50/54 (92.6%) controls and 70/70 (100%) boosted individuals.
      CONCLUSIONS: The planned introduction in the UK of an adolescent booster of MenC
      conjugate vaccine in 2013 is likely to provide sustained protection against MenC
      disease. TRIAL REGISTRATION: Registered on ClinicalTrials.gov (NCT01459432).

PMID- 23853001
TI  - Acute leukaemia presenting with isolated bone pain.

PMID- 23853002
TI  - Prescribing liquid medication: can the dose be accurately given?

PMID- 23853003
TI  - Tuberculous paradoxical reaction with bone involvement.

PMID- 23853004
TI  - Acceptability of different oral formulations in infants and preschool children.
AB  - OBJECTIVE: Liquid medicines are easy to swallow. However, they may have
      disadvantages, such as a bad taste or refrigerated storage conditions. These
      disadvantages may be avoided by the use of oral solid medicines, such as powders
      or tablets. The aim of this study was to investigate the acceptability of and
      preference among four oral formulations in domiciliary infants and preschool
      children in The Netherlands. METHODS: Parents administered four oral placebo
      dosage forms that were aimed at a neutral taste, at home, to their child (1-4
      years of age) twice on one day following a randomised cross-over design: small (4
      mm) tablet, powder, suspension and syrup. They were asked to report the child's
      acceptability by a score on a 10 cm visual analogue scale (VAS score) and by the
      result of the intake. At the end of the study, they were asked to report the
      preference of the child and themselves. RESULTS: 183 children were included and
      148 children were evaluated. The data revealed a period/cross-over effect. The
      estimate of the mean VAS score was significantly higher for the tablet than for
      the suspension (tablet 9.39/9.01; powder 8.84/8.20, suspension 8.26/7.90, syrup
      8.35/8.19; data day 1/all days). The estimate of the mean number of intakes fully
      swallowed was significantly higher for the tablet than for the other formulations
      (all p values <0.05). Children and parents preferred the tablet and syrup over
      the suspension and the suspension over the powder (all p values <0.05).
      CONCLUSIONS: All formulations were well accepted. The tablets were the best
      accepted formulation; the tablets and syrup the most preferred. TRIAL
      REGISTRATION NUMBER: ISRCTN63138435.

PMID- 23853005
TI  - Regional innervation of the heart in the goldfish, Carassius auratus: a confocal
      microscopy study.
AB  - The intracardiac nervous system represents the final common pathway for autonomic
      control of the vertebrate heart in maintaining cardiovascular homeostasis. In
      teleost fishes, details of the organization of this system are not well
      understood. Here we investigated innervation patterns in the heart of the
      goldfish, a species representative of a large group of cyprinids. We used
      antibodies against the neuronal markers zn-12, acetylated tubulin, and human
      neuronal protein C/D, as well as choline acetyltransferase, tyrosine hydroxylase,
      nitric oxide synthetase, and vasoactive intestinal polypeptide (VIP) to detect
      neural elements and their transmitter contents in wholemounts and sections of
      cardiac tissue. All chambers of the heart were innervated by choline
      acetyltransferase-positive axons, implying cholinergic regulation; and by
      tyrosine hydroxylase-containing axons, implying adrenergic regulation. The mean
      total number of intracardiac neurons was 713 +/- 78 (SE), nearly half of which
      were cholinergic. Neuronal somata were mainly located in a ganglionated plexus
      around the sinoatrial valves. Somata were contacted by cholinergic, adrenergic,
      nitrergic, and VIP-positive terminals. Putative pacemaker cells, identified by
      immunoreactivity for hyperpolarization activated, cyclic nucleotide-gated channel
      4, were located in the base of the sinoatrial valves, and this region was densely
      innervated by cholinergic and adrenergic terminals. We have shown that the
      goldfish heart possesses the necessary neuroanatomical substrate for fine, region
      by-region autonomic control of the myocardial effectors that are involved in
      determining cardiac output.

PMID- 23853006
TI  - Ventilatory response to nitrogen multiple-breath washout in infants.
AB  - BACKGROUND: Nitrogen multiple-breath washout (N2 MBW) using 100% oxygen (O2) has
      regained interest to assess efficiency of tracer gas clearance in, for example,
      children with Cystic Fibrosis (CF). However, the influence of hyperoxia on the
      infants' respiratory control is unclear. We assessed safety and impact on
      breathing pattern from hyperoxia, and if exposure to 40% O2 first induces
      tolerance to subsequent 100% O2 for N2 MBW. METHODS: We prospectively enrolled 39
      infants aged 3-57 weeks: 15 infants with CF (8 sedated for testing) and 24
      healthy controls. Infants were consecutively allocated to the protocols
      comprising of 100% O2 or 40/100% O2 administered for 30 breaths. Lung function
      was measured using an ultrasonic flowmeter setup. Primary outcome was tidal
      volume (VT). RESULTS: None of the infants experienced apnea, desaturation, or
      bradycardia. Both protocols initially induced hypoventilation. VT temporarily
      declined in 33/39 infants across 10-25 breaths. Hypoventilation occurred
      independent of age, disease, and sedation. In the new 40/100% O2 protocol, VT
      returned to baseline during 40% O2 and remained stable during 100% O2 exposure.
      End-tidal carbon dioxide monitored online did not change. CONCLUSION: The
      classical N2 MBW protocol with 100% O2 may change breathing patterns of the
      infants. The new protocol with 40% O2 induces hyperoxia-tolerance and does not
      lead to changes in breathing patterns during later N2 washout using 100% O2. Both
      protocols are safe, the new protocol seems an attractive option for N2 MBW in
      infants.

PMID- 23853007
TI  - Cannonball shadow in the lungs and pulmonary embolism in a young man.

PMID- 23853008
TI  - Herpes zoster ophthalmicus progressing to encephalitis: beware pain preceding the
      rash.
AB  - We present a challenging case in which the dermatomal pain associated with herpes
      zoster ophthalmicus preceded the cutaneous rash by several days. It thus
      highlights the need to consider this diagnosis among the differentials for severe
      unilateral headache in the elderly. The patient unfortunately progressed to
      develop encephalitis, an uncommon but serious complication of zoster reactivation
      and a reminder that this remains an important cause of morbidity and mortality in
      the elderly population. 

PMID- 23853009
TI  - Huntington's disease masquerading as spinocerebellar ataxia.
AB  - Huntington's disease (HD) is a neurodegenerative disorder of the central nervous
      system characterised by the presence of choreic abnormal movements, behavioural
      or psychiatric disturbances and dementia. Noteworthy, despite atypical motor
      symptoms other than chorea have been reported as initial presentation in some
      patients, a very few number of HD patients, presenting at onset mostly cerebellar
      dysfunction masquerading dominant spinocerebellar ataxias (SCA), were
      occasionally reported. We report the case of a 42-year-old man with a 5-year
      history of gait disturbance, dysarthria and cognitive impairment and familial
      antecedents of dementia and movement disorders. Initially the clinical picture
      suggested the diagnosis of a dominant SCA, but finally a diagnosis of HD was made
      based on the molecular evidence of abnormal 39 Cytosine-Adenine-Guanine (CAG)
      repeats in exon 1 of Huntingtin gene. The authors highlight the importance of
      suspecting HD in the aetiology of spinocerebellar ataxias when dementia is a
      prominent feature in the proband or their family. 

PMID- 23853010
TI  - Aspiration thrombectomy in concert with stent thrombectomy.
AB  - In the SWIFT and TREVO 2 trials, aspiration thrombectomy was not able to be
      performed. Outside these studies, in post-market application, the interventionist
      can use aspiration thrombectomy in addition to stent device thrombectomy. This
      technique is described in detail in the present report. Combined
      aspiration/stentriever thrombectomy may improve recanalization efforts, simplify
      a second thrombectomy attempt if necessary and may limit distal embolization. 

PMID- 23853011
TI  - Paget-Schrotter syndrome and complications of management.
AB  - An 18-year-old man presented to the emergency department with an acutely swollen
      right upper limb having spent the previous day canoeing. Venography confirmed
      right subclavian venous thrombosis at middle one-third of right clavicle with no
      evidence of cervical rib or other structural abnormalities. Following
      heparinisation, catheter directed thrombolysis was performed which restored
      luminal flow. Postprocedure the patient developed spontaneous small-volume
      haemoperitoneum and acute renal failure. The patient was admitted to the
      intensive care unit for haemodialysis and supportive management. The patients'
      renal function improved and he was discharged well following his 28th day of
      admission. Paget-Schroetter syndrome or effort thrombosis involves subclavian
      venous thrombosis associated with strenuous activity of upper extremities. In
      these cases, catheter directed thrombolysis with first rib resection provides
      greater patency rate than anticoagulation therapy alone. Acute kidney injury
      following mechanical thrombolysis is rarely reported in the literature. 

PMID- 23853012
TI  - Fracture tooth fragment reattachment.
AB  - Coronal fractures of the anterior teeth are a common form of dental trauma and
      its sequelae may impair the establishment and accomplishment of an adequate
      treatment plan. Among the various treatment options, reattachment of a crown
      fragment is a conservative treatment that should be considered for crown
      fractures of anterior teeth. This clinical case reports the management of two
      coronal tooth fracture cases that were successfully treated using tooth fragment
      reattachment using glass-fibre-reinforced composite post. 

PMID- 23853013
TI  - Cardiac involvement as the main presenting feature in eosinophilic granulomatosis
      with polyangiitis.
AB  - Eosinophilic granulomatosis with polyangiitis is usually characterised by asthma,
      allergic rhinitis and peripheral eosinophilia. Presentations can vary greatly
      especially when there is cardiac involvement as demonstrated in these two case
      reports. Patient A initially presented to casualty with severe sinus pain and was
      diagnosed with severe sinonasal polyposis. After routine nasal polypectomy he had
      a cardiac arrest and was transferred to intensive care. Patient B presented to
      his general practitioner with a 4-week history of breathlessness, joint pain and
      a rash resulting in admission to hospital. Both patients had significant
      eosinophilia on routine bloods. High-sensitivity troponin T levels were raised in
      both; however, patient B's was significantly higher. Patient A had a large
      pericardial effusion on echo, the aspirate of which revealed numerous
      eosinophils. Patient B's echo was normal. Patient A's cardiac MRI was normal
      while Patient B's revealed myocarditis. Both were successfully treated with
      intravenous methylprednisolone and cyclophosphamide. 

PMID- 23853014
TI  - Asymptomatic lunotriquetral coalition: an incidental radiographic finding.

PMID- 23853015
TI  - Hybrid peripheral ameloblastoma of cheek mucosa.
AB  - An unusual case of large buccal tumour has been described. The lesion was
      clinically compatible with a squamous cell carcinoma, but it had pathological
      features of an ameloblastoma arising in the soft tissues. Only few cases of
      extragingival peripheral ameloblastoma were found in a review of the literature.
      Possible origins of these tumours are still debatable. 

PMID- 23853016
TI  - Skull base osteomyelitis presenting with an isolated hypoglossal nerve palsy.
AB  - This is the first case of skull base osteomyelitis presenting with isolated
      bilateral hypoglossal nerve palsy reported in the literature. A 75-year-old man
      presented with tongue paralysis without any other cranial nerve palsy. He was
      otherwise well apart from recently having a high prostate-specific antigen level
      recorded. Investigations for malignancy or cerebrovascular insult were negative
      with the diagnosis of skull base osteomyelitis confirmed using CT. Following
      treatment with intravenous antibiotics for 6 weeks, symptoms resolved. 

PMID- 23853017
TI  - Anaphylactic shock and cardiac arrest caused by thiamine infusion.
AB  - Parenteral thiamine has a very high safety profile. The most common adverse
      effect is local irritation; however, anaphylactic or anaphylactoid reactions may
      occur, mostly related to intravenous administration. We describe a 44-year-old
      man, a chronic alcoholic, who was admitted with alcohol intoxication and
      developed cardiac arrest due to anaphylactic shock following intravenous thiamine
      infusion. The patient was successfully resuscitated after 15 min and repeated
      epinephrine administrations. He was discharged in good health after 14 days. This
      case report emphasises both the importance of recognising the symptoms of
      anaphylaxis and the fact that facilities for treating anaphylaxis and
      cardiopulmonary resuscitation should be available when thiamine or for that
      matter, any drug is given in-hospital. 

PMID- 23853018
TI  - Cementifying fibroma.
AB  - Cementifying fibroma is considered as a benign, osseous tumour, which arises from
      the periodontal ligament and is composed of varying amounts of cementum, bone and
      fibrous tissue. It is very closely related to other fibro-osseous lesions like
      fibrous dysplasia, cemental periapical dysplasia and other calcifying odontogenic
      cysts and tumour. We report a case of this entity along with differentiating
      radiographic features that set it apart from other fibro-osseous lesions. 

PMID- 23853019
TI  - Jung's archetype, 'The Wounded Healer', mental illness in the medical profession
      and the role of the health humanities in psychiatry.
AB  - Carl Jung used the term, 'The Wounded Healer' as an archetype to describe doctors
      who have suffered from an illness. Reading and writing autobiographical
      narratives of the 'Wounded Healer' is gaining popularity among doctors with
      mental illness as an effective form of adjunctive therapy. Moreover, reading
      autobiographical narratives of psychopathology sufferers can 'augment' service
      providers' humanity by offering valuable qualitative insights into minds
      afflicted with a psychiatric disorder. The primary author, a doctor of Middle
      Eastern descent practicing in the UK, composed an autobiographical narrative
      about his personal experiences with oscillations in his mood in an attempt to
      illustrate the cultural, religious and psychosocial factors that influence
      disease detection, progression, treatment and outcome. An inordinate amount of
      misconceptions about mental illness abound. We hope that this manuscript will
      help to lessen the stigma associated with those who suffer from psychopathology
      (particularly doctors) and encourage sufferers to engage with the appropriate
      services. 

PMID- 23853020
TI  - Bilateral renal cell carcinoma in a paediatric patient with tuberous sclerosis
      complex.
AB  - Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder
      characterised by seizures, mental retardation and hamartoma formation in multiple
      organs, mainly in the brain, skin, kidney, liver, lung and heart. Renal
      manifestations occur in about 60-80% of all patients with TSC and their rate
      increases with age. We report the case of a 17-year-old boy with tuberous
      sclerosis who presented with abdominal pain associated with kidney failure.
      Investigation revealed bilateral renal lesions, suggesting angiomyolipomas. On
      further work-up, malignancy was suspected and the patient underwent bilateral
      partial nephrectomy with histological diagnosis of bilateral renal cell
      carcinoma. This is a rare complication of TSC, particularly in a paediatric
      setting. Adequate surveillance of kidney disorders in patients with TSC is
      warranted, to guarantee an early diagnosis and treatment. 

PMID- 23853021
TI  - Cutis verticis gyrata as a clinical manifestation of Touraine-Solente-Gole'
      syndrome (pachydermoperiostosis).
AB  - Cutis verticis gyrata is a descriptive term for a condition of the scalp
      consisting of deep grooves and convolutions that resemble the surface of the
      brain. We present a case of a 22-year-old man who presented with pain and
      swelling of both knees and hands. Enlarged wrists, ankles and feet were also
      noted, along with facial seborrhoea, thickening of the skin and deformity of the
      fingers. Physical examination of the scalp showed a cerebriform appearance with
      accentuating folds and deep furrows (cutis verticis gyrata), thickening in the
      face, frontal and parietal regions. Bone enlargement of the hands, knees, ankles
      and feet was also found. Secondary causes of pachydermoperiostosis were negative.

PMID- 23853022
TI  - Neuroleptic malignant syndrome associated with haloperidol use in critical care
      setting: should haloperidol still be considered the drug of choice for the
      management of delirium in the critical care setting?
AB  - A 48-year-old man was brought to the emergency department because of
      intoxication. The patient was in respiratory distress, subsequently intubated for
      airway protection. On hospital day 5, he was diagnosed with delirium. Haloperidol
      was initiated at 5 mg intravenous every 6 h and titrated up to a dose of 60 mg
      /day over 5 days. On hospital day 18, his temperature peaked to 107.1 degrees F.
      Other symptoms included mental status change, muscular rigidity and autonomic
      dysfunction. Neuroleptic malignant syndrome (NMS) associated with haloperidol was
      suspected. No other causes for these symptoms were present. Concurrent
      medications were reviewed and ruled out for possible drug-induced fever.
      Haloperidol was discontinued and dantrolene and bromocriptine was initiated. The
      temperature decreased to 102.2 degrees F within 3 h and other symptoms resolved
      overtime. The temporal relationship between the patient's fever decline with the
      discontinuation of haloperidol, and improvement with dantrolene and
      bromocriptine, the diagnosis was believed to be haloperidol-induced NMS. 

PMID- 23853023
TI  - Capsular warning syndrome.
AB  - We present a case of a 72-year-old man who presented with fluctuating right-sided
      weakness and numbness. This was characterised by episodic sudden onset weakness
      with resolution of symptoms in between. His symptoms and signs were becoming
      persistent despite the addition of dual antiplatelet therapy. The history we
      describe is classical of capsular warning syndrome. The patient went on to have
      further definitive neuroimaging which revealed a pontine infarct, rather than the
      expected capsular infarct. We discuss the importance of capsular warning
      syndrome, the proposed pathophysiological mechanisms and different locations of
      infarction in previous cases of capsular warning syndrome. We also discuss the
      lack of consensus (within the literature) in treatment options which are used to
      try and prevent a completed stroke occurring in cases of capsular warning
      syndrome. 

PMID- 23853024
TI  - Neurological improvement following reinstitution of a low phenylalanine diet
      after 20 years in established phenylketonuria.
AB  - A 41-year-old woman had meaningful functional improvement following reinstitution
      of a low phenylalanine diet. She was diagnosed at birth with phenylketonuria and
      followed strict dietary adherence till the age of 16. Thereafter the diet was
      discontinued. She subsequently presented with subacute profound visual loss,
      cognitive dysfunction and paraparesis such that she was bed bound requiring full
      nursing care. Following dietary intervention there was meaningful improvement
      such that she was no longer demented and while her vision remains poor she is now
      independent for activities of daily living. This case report suggests that
      consideration of reimplementation of dietary intervention is warranted even after
      a prolonged period of time. 

PMID- 23853025
TI  - Bilateral radix entomolaris with primary and permanent mandibular first molars.
AB  - Dental practitioners should be aware of the morphological dental anomalies like
      additional roots; their location, incidence and associated unusual root canal
      morphology. They should also carefully interpret the intraoral radiographs so
      that such anomalies do not go unnoticed. 

PMID- 23853026
TI  - Pleuroperitoneal leak in a peritoneal dialysis patient.

PMID- 23853027
TI  - A foreign body of the larynx misdiagnosed as vocal cord paralysis.
AB  - Foreign bodies in the aerodigestive tract continue to be a common problem that
      contribute significantly to high morbidity and mortality all over the world.
      Laryngeal foreign bodies may present with less severe symptoms compared with
      lower respiratory tract foreign bodies, resulting in misdiagnosis, confusion and
      delay in diagnosis. Rigid endoscopy with forceps removal under general
      anaesthesia is the preferred management modality. This case is described to show
      the importance of a detailed history and examination including X-ray neck in
      children to rule out any radiopaque laryngeal foreign body as a delay in
      diagnosis and management can lead to life-threatening complications. 

PMID- 23853028
TI  - Stone in ureterocele peeping through ureteric orifice.

PMID- 23853029
TI  - AFQ056 in Parkinson patients with levodopa-induced dyskinesia: 13-week,
      randomized, dose-finding study.
AB  - AFQ056 is a novel, selective metabotropic glutamate receptor 5 antagonist. This
      was a 13-week, double-blind, placebo-controlled study. Patients with Parkinson's
      disease and moderate-to-severe levodopa (l-dopa)-induced dyskinesia who were
      receiving stable l-dopa/anti-parkinsonian treatment and were not currently
      receiving amantadine were randomized to receive either AFQ056 (at doses of 20,
      50, 100, 150, or 200 mg daily) or placebo (1:1:1:1:2:3 ratio) for 12 weeks. The
      primary outcome was the modified Abnormal Involuntary Movements Scale. Secondary
      outcomes included the 26-item Parkinson's Disease Dyskinesia Scale, the
      Patient's/Clinician's Global Impression of Change, and the Unified Parkinson's
      Disease Rating Scale parts III (motor evaluation) and IV (severity of motor
      complications). Safety was assessed. In total, 98 of 133 (73.7%) AFQ056-treated
      patients and 47 of 64 (73.4%) patients in the placebo group completed the study.
      Baseline characteristics were comparable. Patients randomized to AFQ056 200 mg
      daily administered in 2 doses demonstrated significant improvements at Week 12 on
      the modified Abnormal Involuntary Movements Scale compared with placebo
      (difference, -2.8; 95% confidence interval [CI], -5.2, -0.4; P = 0.007). Based on
      final actual doses, there was a dose-response relationship on the modified
      Abnormal Involuntary Movements Scale, with 200 mg daily demonstrating the most
      robust effect (difference, -3.6; 95% CI, -7.0, -0.3; P = 0.012). Improvements in
      dyskinesia were supported by change on Unified Parkinson's Disease Rating Scale
      part IV item 32 (50 mg daily: difference, -0.7; 95% CI, -1.1, -0.2; P = 0.003;
      200 mg daily: difference, -0.5; 95% CI, -0.8, -0.1; P = 0.005). No significant
      changes were observed on the 26-item Parkinson's Disease Dyskinesia Scale, the
      Unified Parkinson's Disease Rating Scale part IV item 33 or items 32 and 33, or
      the Patient's/Clinician's Global Impression of Change. Unified Parkinson's
      Disease Rating Scale part III scores were not significantly changed, indicating
      no worsening of motor symptoms. The most common adverse events (with incidence
      greater with AFQ056 than with placebo) were dizziness, hallucination, fatigue,
      nasopharyngitis, diarrhea, and insomnia. AFQ056 demonstrated anti-dyskinetic
      efficacy in this population without worsening underlying motor symptoms. These
      results will guide dose selection for future clinical trials.

PMID- 23853030
TI  - Comment on: fifteen minute consultation: a structured approach to the management
      of facial paralysis in a child.

PMID- 23853031
TI  - Risk factors for drug-resistant bacterial pneumonia in older patients
      hospitalized with pneumonia in a Chinese population.
AB  - BACKGROUND: The relationship between healthcare-associated pneumonia (HCAP) and
      resistant bacteria is unclear. The aim of this study was to identify the risk
      factors for pneumonia caused by drug-resistant bacteria (DRB). METHODS: A
      prospective cohort study was conducted at a tertiary teaching hospital in Hong
      Kong. Consecutive older patients (aged >=65 years) were hospitalized with
      pneumonia from January 2004 to June 2005. DRB comprised methicillin-resistant
      Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, extended-spectrum beta
      lactamase (ESBL) producing Enterobacteriaceae and Acinetobacter baumannii.
      RESULTS: The entire cohort consisted of 1176 older patients. Of 472 (40.1%)
      patients with etiological diagnosis established, bacterial pneumonia was found in
      354 (30.1%) cases. DRB were isolated in 48 patients: P. aeruginosa (41), MRSA (5)
      and ESBL producing enteric bacilli (3). Co-infection with P. aeruginosa and MRSA
      was found in one patient. The prevalence of DRB in culture-positive pneumonia was
      20.1% (48/239). Patients with DRB were more likely to have limitation in
      activities of daily living, bronchiectasis, dementia, severe pneumonia, recent
      hospitalization and recent antibiotic use. Logistic regression revealed that
      bronchiectasis [relative risk (RR) 14.12, P = 0.002], recent hospitalization (RR
      4.89, P < 0.001) and severe pneumonia (RR 2.42, P = 0.010) were independent
      predictors of drug-resistant bacterial pneumonia. CONCLUSION: Recent
      hospitalization is the only risk factor for HCAP which is shown to be associated
      with DRB. Nursing home residence is not a risk factor. The concept of HCAP may
      not be totally applicable in Hong Kong where the prevalence of drug-resistant
      pathogens in pneumonia is low.

PMID- 23853033
TI  - Effect of zircon-based tricolor pigments on the color, microstructure, flexural
      strength and translucency of a novel dental lithium disilicate glass-ceramic.
AB  - The purpose of this study was to investigate the effect of zircon-based tricolor
      pigments (praseodymium zircon yellow, ferrum zircon red, and vanadium zircon
      blue) on the color, thermal property, crystalline phase composition,
      microstructure, flexural strength, and translucency of a novel dental lithium
      disilicate glass-ceramic. The pigments were added to the glass frit, milled,
      pressed, and sintered. Ninety monochrome samples were prepared and the colors
      were analyzed. The effect of the pigments on thermal property, crystalline phase
      composition, and microstructure were determined by differential scanning
      calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy
      (SEM), respectively. Addition of the pigments resulted in the acquisition of
      subtractive primary colors as well as tooth-like colors, and did not demonstrate
      significant effects on the thermal property, crystalline phase composition,
      microstructure, and flexural strength of the experimental glass-ceramic. Although
      significant differences (p < 0.01) were observed between the translucencies of
      the uncolored and 1.0 wt % zircon-based pigment colored ceramics, the
      translucencies of the latter were sufficient to fabricate dental restorations.
      These results indicate that the zircon-based tricolor pigments can be used with
      dental lithium disilicate glass-ceramic to produce abundant and predictable tooth
      like colors without significant adverse effects, if mixed in the right
      proportions.

PMID- 23853032
TI  - Neural bases of pharmacological treatment of nicotine dependence - insights from
      functional brain imaging: a systematic review.
AB  - BACKGROUND: Nicotine dependence is difficult to treat, and the biological
      mechanisms that are involved are not entirely clear. There is an urgent need to
      develop better drugs and more effective treatments for clinical practice. A
      critical step towards accelerating progress in medication development is to
      understand the neurobehavioral effects of pharmacotherapies on clinical
      characteristics associated with nicotine dependence. OBJECTIVES: This review
      sought to summarize the functional magnetic resonance imaging (fMRI) literature
      on smoking cessation with the aim to better understand the neural processes
      underlying the effects of nicotinic and non-nicotinic pharmacological smoking
      cessation treatments on specific symptoms of nicotine dependence and withdrawal.
      DATA SOURCES: We conducted a search in Pubmed, Web of Science and PsycINFO
      databases with the keywords 'fMRI' or 'functional magnetic resonance imaging' and
      'tobacco' or 'nicotine' or 'smok*'. The date of the most recent search was May
      2012. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: The original
      studies that were included were those of smokers or nicotine-dependent
      individuals, published in the English language, with pharmacological treatment
      for nicotine dependence and use of fMRI with blood oxygen level-dependent (BOLD)
      imaging or continuous arterial spin labelling (CASL). No date limit was applied.
      STUDY APPRAISAL AND SYNTHESIS METHODS: Two of the authors read the abstracts of
      all studies found in the search (n = 1,260). The inclusion and exclusion criteria
      were applied, and 1,224 articles were excluded. In a second step, the same
      authors read the remaining 36 studies. Nineteen of the 36 articles were excluded.
      The results were tabulated by the number of individuals and their mean age, the
      main sample characteristics, smoking status, study type and methodology, and the
      main fMRI findings. RESULTS: Seventeen original fMRI studies involving
      pharmacological treatment of smokers were selected. The anterior and posterior
      cingulate cortex, medial and lateral orbitofrontal cortex, ventral striatum,
      amygdala, thalamus and insula are heavily involved in the maintenance of smoking
      and nicotine withdrawal. The effects of varenicline and bupropion in alleviating
      withdrawal symptoms and decreasing smoking correlated with modulation of the
      activities of these areas. Nicotine replacement therapy seems to improve
      cognitive symptoms related to withdrawal especially by modulating activities of
      the default-network regions; however, nicotine replacement does not necessarily
      alter the activities of neural circuits, such as the cingulate cortices, that are
      associated with nicotine addiction. LIMITATIONS: The risk of bias in individual
      studies, and across studies, was not assessed, and no method of handling data and
      combining results of studies was carried out. Most importantly, positron emission
      tomography (PET) studies were not included in this review. CONCLUSIONS AND
      IMPLICATION OF KEY FINDINGS: fMRI studies delineate brain systems that contribute
      to cognitive deficits and reactivity to stimuli that generate the desire to
      smoke. Nicotinic and non-nicotinic pharmacotherapy may reduce smoking via
      distinct neural mechanisms of action. These findings should contribute to the
      development of new medications and discovery of early markers of the therapeutic
      response of cigarette smokers.

PMID- 23853039
TI  - MC3T3-E1 and RAW264.7 cell response to hydroxyapatite and alpha-type alumina
      adsorbed with bovine serum albumin.
AB  - Initial cell responses following implantation are important for inducing
      osteoconductivity. We investigated cell adhesion, spreading, and proliferation in
      response to native and bovine serum albumin (BSA)-adsorbed disc of hydroxyapatite
      (HA) or alpha-type alumina (alpha-Al2O3) using mouse MC3T3-E1 osteoblastic cells
      and mouse RAW264.7 macrophages. The adsorbed BSA inhibited adhesion and spreading
      of MC3T3-E1 cells, but did not affect MC3T3-E1 cell proliferation on HA and alpha
      Al2O3 substrates. Thus, MC3T3-E1 cells quickly adhere to original HA before cell
      binding is impeded by adsorption of BSA in quantities sufficient to inhibit the
      adhesion of MC3T3-E1 cells. The adsorbed BSA inhibits adhesion of RAW264.7 cells
      to alpha-Al2O3, but not to HA. BSA adsorption does not affect RAW264.7 cell
      spreading and proliferation on both HA and alpha-Al2O3 substrates. Thus, BSA
      adsorbed on HA stimulates a different cell response than alpha-Al2O3. Moreover,
      quick adherence of osteoblast cells and monocyte-macrophage lineage cells plays a
      role in HA osteoconductivity.

PMID- 23853040
TI  - The macamide N-3-methoxybenzyl-linoleamide is a time-dependent fatty acid amide
      hydrolase (FAAH) inhibitor.
AB  - The Peruvian plant Lepidium meyenii (Maca) has been shown to possess
      neuroprotective activity both in vitro and in vivo. Previous studies have also
      demonstrated the activity of the pentane extract and its macamides, the most
      representative lipophilic constituents of Maca, in the endocannabinoid system as
      fatty acid amide hydrolase (FAAH) inhibitors. One of the most active macamides, N
      3-methoxybenzyl-linoleamide, was studied to determine its mechanism of
      interaction with FAAH and whether it has inhibitory activity on mono-acyl
      glycerol lipase (MAGL), the second enzyme responsible for endocannabinoid
      degradation. Macamide concentrations from 1 to 100 MUM were tested using FAAH and
      MAGL inhibitor assay methods and showed no effect on MAGL. Tests with other
      conditions were performed in order to characterize the inhibitory mechanism of
      FAAH inhibition. N-3-methoxybenzyl-linoleamide displayed significant time
      dependent and dose-dependent FAAH inhibitory activity. The mechanism of
      inhibition was most likely irreversible or slowly reversible. These results
      suggest the potential application of macamides isolated from Maca as FAAH
      inhibitors, as they might act on the central nervous system to provide analgesic,
      anti-inflammatory, or neuroprotective effects, by modulating the release of
      neurotransmitters.

PMID- 23853041
TI  - Amyloid precursor protein mutation disrupts reproductive experience-enhanced
      normal cognitive development in a mouse model of Alzheimer's disease.
AB  - Women experience dramatic changes in hormones, mood and cognition through
      different periods of their reproductive lives, particularly during pregnancy and
      giving birth. While limited human studies of early pregnancy and motherhood
      showed alteration of cognitive functions in later life, researches on rodents
      showed a persistent improvement of learning and memory performance in females
      with history of giving birth compared to virgin controls. Alzheimer's disease
      (AD), the most common dementia in elderly, is more prevalent in women than in
      men. One of the risk factors is related to the sharp reduction of estrogen in
      aged women. It is unknown whether the history of fertility activity plays any
      roles in altering risk of AD in females, such as altering cognitive function.
      Would reproductive experience alter the risk of AD in females? If so, what might
      be the mechanisms of the change? In this study, we examined the effects of
      reproductive experience on cognitive function in an AD transgenic mouse model
      (APP23) and age-matched wild-type non-transgenic control mice (WT). Our data
      showed an age-dependent effect of reproductive experience on learning and memory
      activity between breeders (had one or more litters) and non-breeders (virgins).
      More importantly, our data, for the first time, demonstrated a genotype-dependent
      effect of parity on cognitive function between APP23 and WT mice. At the age of
      12 months, WT breeders outperform non-breeders in spatial working and reference
      memory while APP23 breeders performed worse in spatial learning and memory than
      age-matched APP23 non-breeders. These genotype- and age-dependent effects of
      reproductive activity on cognitions are significantly associated with changes of
      neuropathology of AD in the APP23 mice, expression of proteins related to
      synaptic plasticity and cognitive functions in the brain. 

PMID- 23853043
TI  - N-heterocyclic carbene organocatalysts for dehydrogenative coupling of silanes
      and hydroxyl compounds.
AB  - Go organic! N-Heterocyclic carbene (NHC) 1,3-diisopropyl-4,5-dimethylimidazol-2
      ylidene (IiPr) has been found to be an efficient and selective catalyst for the
      dehydrogenative coupling of a wide range of silanes and hydroxyl groups to form
      Si?O bonds under mild and solvent-free conditions. Mechanistic studies indicated
      that the activation of hydroxyl groups by the NHC is the most plausible initial
      step for the process. 

PMID- 23853044
TI  - Effect of different approaches to target force on transcranial magnetic
      stimulation responses.
AB  - INTRODUCTION: The aim of this study was to determine whether the manner in which
      a target force is approached can influence the electromyographic (EMG) and
      mechanical parameters evoked by transcranial magnetic stimulation (TMS) during
      brief muscle contractions. METHODS: The amplitude of motor-evoked potentials
      (MEP) and superimposed twitch and the duration of the silent period were recorded
      in 8 healthy participants in response to TMS delivered during brief isometric
      voluntary contractions of the quadriceps maintaining a target force (10% and 50%
      of maximal voluntary force) or gradually increasing or decreasing to reach this
      point. RESULTS: MEP and superimposed twitch, unlike the silent period, are
      influenced by the manner of reaching a low force. CONCLUSIONS: Clear instructions
      must be provided to research participants and patients. Rapidly increasing to a
      target force without exceeding it and maintaining the force before the delivery
      of TMS results in stable, representative MEP amplitudes.

PMID- 23853045
TI  - Flow cytometric characterization of tumor subpopulations in three sublines of the
      Dunning R3327 rat prostate tumor model.
AB  - BACKGROUND: Subsets of tumor cells were characterized by mapping DNA ploidy
      patterns in correlation with established cell surface markers in three non
      treated sublines of the Dunning R3327 prostate tumor system representing
      different progressional stages. METHODS: Flow cytometry was used to analyze DNA
      index, cell cycle distribution as well as multiparametric aquisition of single
      and combined cell surface markers in single cell suspensions of frozen tumor
      tissues. RESULTS: The three Dunning prostate tumor sublines clearly differ in
      their ploidy status. In addition each tumor subline displays a characteristic
      cell surface marker profile, which is correlated with the cell cycle phase and
      the amount of genomic alterations. CONCLUSIONS: In a feasibility study we have
      shown that cross-reacting antibodies to human cell surface markers stain discrete
      tumor subpopulations in three sublines of the Dunning tumor model. Although it
      remains presently uncertain, which cell surface markers are most suitable for
      cell sorting to display cancer initiating (CIC) properties following subcutaneous
      or orthotopic grafting, the model may be useful for mechanistic investigations of
      putative stem-like tumor subpopulations and their significance in response to
      radio- or chemotherapy.

PMID- 23853042
TI  - Targeting the mTOR signaling network for Alzheimer's disease therapy.
AB  - The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine
      kinase that can sense environmental stimuli such as growth factors, energy state,
      and nutrients. It is essential for cell growth, proliferation, and metabolism,
      but dysregulation of mTOR signaling pathway is also associated with a number of
      human diseases. Encouraging data from experiments have provided sufficient
      evidence for the relationship between the mTOR signaling pathway and Alzheimer's
      disease (AD). Upregulation of mTOR signaling pathway is thought to play an
      important role in major pathological processes of AD. The mTOR inhibitors such as
      rapamycin have been proven to ameliorate the AD-like pathology and cognitive
      deficits effectively in a broad range of animal models. Application of mTOR
      inhibitors indicates the potential value of reducing mTOR activity as an
      innovative therapeutic strategy for AD. In this review, we will focus on the
      recent process in understanding mTOR signaling pathway and the vital involvement
      of this signaling pathway in the pathology of AD, and discuss the application of
      mTOR inhibitors as potential therapeutic agents for the treatment of AD. 

PMID- 23853046
TI  - High-dose versus low-dose oxytocin for augmentation of delayed labour.
AB  - BACKGROUND: A major cause of failure to achieve spontaneous vaginal birth is
      delay in labour due to presumed inefficient uterine action. Oxytocin is given to
      increase contractions and high-dose regimens may potentially increase the number
      of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the
      uterus, there is a possibility of increased adverse events. OBJECTIVES: To
      compare starting dose and increment dose of oxytocin for augmentation for women
      delayed in labour to determine whether augmentation by high-dose regimens of
      oxytocin improves labour outcomes and to examine the effect on both
      maternal/neonatal outcomes and women's birth experiences. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May
      2013) and reference lists of retrieved studies. SELECTION CRITERIA: We included
      all randomised and quasi-randomised controlled trials for women in delayed labour
      requiring augmentation by oxytocin comparing high-dose regimens (defined as
      starting dose and increment of equal to or more than 4 mU per minute) with low
      dose regimens (defined as starting dose and an increment of less than 4 mU per
      minute). Increase interval: between 15 and 40 minutes. The separation of low- and
      high-dose regimens is based on an arbitrary decision. DATA COLLECTION AND
      ANALYSIS: Four review authors undertook assessment of trial eligibility, risk of
      bias, and data extraction independently. MAIN RESULTS: We included four studies
      involving 644 pregnant women. Three studies were randomised controlled trials and
      one trial was a quasi-randomised study. A higher dose of oxytocin was associated
      with a significant reduction in length of labour reported from one trial (mean
      difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one
      trial, 40 women). There was a decrease in the rate of caesarean section (risk
      ratio (RR) 0.62; 95% CI 0.44 to 0.86 four trials, 644 women) and an increase in
      the rate of spontaneous vaginal birth in the high-dose group (RR 1.35; 95% CI
      1.13 to 1.62, three trials, 444 women), although for both of these outcomes there
      were inconsistencies between studies in the size of effect. When we carried out
      sensitivity analysis (temporarily removing a study at high risk of bias) the
      differences between groups were no longer statistically significantThere were no
      significant differences between high- and low-dose regimens for instrumental
      vaginal birth, epidural analgesia, hyperstimulation, postpartum haemorrhage,
      chorioamnionitis or women's perceptions of experiences. For neonatal outcomes,
      there was no significant difference between groups for Apgar scores, umbilical
      cord pH, admission to special care baby unit, or neonatal mortality. The
      following outcomes were not evaluated in the included studies: perinatal
      mortality, uterine rupture, abnormal cardiotocography, women's pyrexia, dystocia
      and neonatal neurological morbidity. AUTHORS' CONCLUSIONS: Higher-dose regimens
      of oxytocin (4 mU per minute or more) were associated with a reduction in the
      length of labour and in caesarean section, and an increase in spontaneous vaginal
      birth. However, there is insufficient evidence to recommend that high-dose
      regimens are advised routinely for women with delay in the first stage of labour.
      Further research should evaluate the effect of high-dose regimens of oxytocin for
      women delayed in labour and should include maternal and neonatal outcomes as well
      as the effects on women.

PMID- 23853047
TI  - How cations change peptide structure.
AB  - Specific interactions between cations and proteins have a strong impact on
      peptide and protein structure. Herein, we shed light on the nature of the
      underlying interactions, especially regarding effects on the polyamide backbone
      structure. This was done by comparing the conformational ensembles of model
      peptides in isolation and in the presence of either Li(+) or Na(+) by using state
      of-the-art density-functional theory (including van der Waals effects) and gas
      phase infrared spectroscopy. These monovalent cations have a drastic effect on
      the local backbone conformation of turn-forming peptides, by disruption of the
      hydrogen-bonding networks, thus resulting in severe distortion of the backbone
      conformations. In fact, Li(+) and Na(+) can even have different conformational
      effects on the same peptide. We also assess the predictive power of current
      approximate density functionals for peptide-cation systems and compare to results
      with those of established protein force fields as well as high-level quantum
      chemistry calculations (CCSD(T)). 

PMID- 23853048
TI  - Positioning of integrin beta1, caveolin-1 and focal adhesion kinase on the
      adhered membrane of spreading cells.
AB  - We have investigated the relationship between the spreading of anchorage
      dependent cells and the surface-density distribution of plasma membrane adhesion
      proteins. The surface positioning and density of integrin beta1, caveolin-1 (cav
      1), the phosphorylated caveolin-1 (p-cav-1) and the focal adhesion kinase (FAK)
      located on the adhering cell membrane (ACM) of HUVEC cells was studied. Imaging
      with TIRF microscopy was used, which enabled us to observe a few-nanometers-thin
      section of the cell above the plasma membrane in combination with image-based
      analyses. Integrin beta1 and cav-1 have spatial interdependence on the ACM. Cells
      treated with substances that act on cell spreading caused changes in the size of
      the ACM area, as well as a redistribution of several proteins under
      investigation. Changes to the ACM area correlated positively with those to the
      surface density of the cav-1. The high integrin beta1 and the low cav-1 surface
      density, and vice versa, following the treatments show that the presence of one
      of them not only spatially excludes, but also reduces, the occurrence of the
      other protein on the ACM, which indicates a regulative mechanism between integrin
      beta1 and cav-1. 

PMID- 23853049
TI  - High frequency oscillation and airway pressure release ventilation in pediatric
      respiratory failure.
AB  - BACKGROUND: Airway pressure release ventilation (APRV) and high frequency
      oscillatory ventilation (HFOV) are frequently used in acute lung injury (ALI)
      refractory to conventional ventilation. Our aim was to describe our experience
      with APRV and HFOV in refractory pediatric ALI, and to identify factors
      associated with survival. METHODS: We analyzed 104 patients with hypoxemia
      refractory to conventional ventilation transitioned to either APRV or HFOV.
      Demographics, oxygenation index (OI), and PaO2 /FiO2 (PF ratio) were recorded
      before transition to either mode of nonconventional ventilation (NCV) and for
      every 12 hr after transition. RESULTS: Relative to APRV, patients on HFOV were
      younger and had more significant lung disease evidenced by higher OI (28.5 [18.6,
      36.2] vs. 21.0 [15.5, 30.0], P = 0.008), lower PF ratios (73 [59,94] vs. 99
      [76,131], P = 0.002), and more frequent use of inhaled nitric oxide. In
      univariate analysis, HFOV was associated with more frequent neuromuscular
      blockade. Forty-one of 104 patients died on NCV (39.4%). Survivors demonstrated
      improvement in OI 24 hr after transition to NCV, whereas non-survivors did not
      (12.9 [8.9, 20.9] vs. 28.1 [17.6, 37.1], P < 0.001). After controlling for
      immunocompromised status, number of vasopressors, and OI before transition, mode
      of NCV was not associated with mortality. CONCLUSIONS: In a heterogeneous PICU
      population with hypoxemia refractory to conventional ventilation transitioned to
      NCV, improvement in oxygenation at 24 hr was associated with survival.
      Immunocompromised status, number of vasopressor infusions, and the OI before
      transition to NCV were independently associated with survival.

PMID- 23853050
TI  - Whose experience is measured? A pilot study of patient satisfaction demographics
      in pediatric otolaryngology.
AB  - OBJECTIVES/HYPOTHESIS: Despite a national emphasis on patient-centered care and
      cultural competency, minority and low-income children continue to experience
      disparities in health care quality. Patient satisfaction scores are a core
      quality indicator. The objective of this study was to evaluate race and insurance
      related disparities in parent participation with pediatric otolaryngology
      satisfaction surveys. STUDY DESIGN: Observational analysis of patient
      satisfaction survey respondents from a tertiary pediatric otolaryngology
      division. METHODS: Demographics of survey respondents (Press Ganey Medical
      Practice Survey(c)) between January and July 2012 were compared to a clinic
      comparison group using t test and chi-square analyses. Multivariate logistic
      regression analyses were performed to assess likelihood to complete a survey
      based on race or insurance status. RESULTS: A total of 130 survey respondents
      were compared to 1,251 patients in the comparison group. The mean patient age for
      which the parent survey was completed was 5.7 years (6.1 years for the comparison
      group, P = 0.18); 59.2% of children were <= 5 years old. Relative to the
      comparison group, survey respondents were more often white (77.7% vs. 58.1%; P
      <0.001) and privately insured (84.6% vs. 60.8%; P <0.001). Similarly, after
      controlling for confounding variables, parents of children who were white (OR
      1.8, 95% CI 1.13-2.78, P = 0.013) or privately insured (OR 2.9, 95% CI 1.74-4.85,
      P <0.001) were most likely to complete a survey. CONCLUSION: Methods to evaluate
      satisfaction did not capture the racial or socioeconomic patient distribution
      within this pediatric division. These findings challenge the validity of applying
      patient satisfaction scores, as currently measured, to indicate health care
      quality. Future efforts to measure and improve patient experience should be
      inclusive of a culturally diverse population.

PMID- 23853051
TI  - Task-specific tremor in violinists: evidence of coactivation in the 3 to 8 Hz
      frequency range.
AB  - BACKGROUND: Task-specific tremor in musicians severely impairs fine motor
      control. However, little is known about its pathophysiology. Here, we quantify
      electromyography (EMG) properties in primary bowing tremor-in particular,
      muscular coactivation-to determine whether primary bowing tremor affects a
      specific frequency range of coactivation. METHODS: We quantitatively compared EMG
      properties of the wrist muscles between 4 professional violinists who had task
      specific tremor and 4 age-matched healthy controls. RESULTS: We observed bowing
      tremor-specific muscular coactivation in the frequency range of 3 to 8 Hz only in
      the patients but not in the healthy controls. No muscular activity was observed
      at the resonance-frequency range. CONCLUSIONS: Our findings indicate an
      association between coactivation and bowing tremor at a specific frequency range
      (3-8 Hz). The absence of EMG activity and coactivation in the mechanical-reflex
      frequency of the wrist suggests that central mechanisms play a more dominant role
      than mechanical-reflex mechanisms in primary bowing tremor.

PMID- 23853052
TI  - Observation of mode-specific vibrational autodetachment from dipole-bound states
      of cold anions.

PMID- 23853054
TI  - Comparative study of mesenchymal stem cells osteogenic differentiation on low
      temperature biomineralized nanocrystalline carbonated hydroxyapatite and sintered
      hydroxyapatite.
AB  - Hydroxyapatite with different characteristics in terms of morphology and
      chemistry were prepared via conventional sintering and low temperature biomimetic
      mineralization methods. The biomineralization route introduced nanocrystalline
      carbonate-substituted hydroxyapatite (n-CHA) with needle-like crystals ranging 20
      30 nm whereas sintered HA (S-HA) comprised of polygonal grains ranging 2-5 MUm.
      The response of fibroblastic cells was investigated using the extract of the
      samples whereas Wistar rat-derived mesenchymal stem cells (MSCs) were evaluated
      on top of each sample while maintaining in an osteogenic-free medium. The
      proliferation, activity, and morphology of adherent MSCs were determined at
      different culturing periods. The osteogenic differentiation of MSCs was also
      assayed by determining expression of runx2, osteonectin, osteopontin, and
      osteocalcin genes using real time-PCR analysis. The fibroblastic cells exhibited
      better proliferation rate at the presence of n-CHA compared to S-HA. Furthermore,
      the MSCs attached and spread well on both n-CHA and S-HA with better
      proliferation rate and alkaline phosphatase activity on n-CHA. Interestingly, the
      osteogenic differentiation of MSCs on n-CHA was confirmed by the expression of
      bone specific proteins whereas poor expression of these proteins was detected for
      the cells on S-HA. The results showed that the role of morphology, crystallinity,
      and chemistry of hydroxyapatite is crucial for osteogenesis differentiation of
      MSCs. The results predict osteoinductivity of n-CHA, because MSCs differentiation
      occurred at the absence of osteogenic medium. However, in vivo data are also
      required to support this suggestion.

PMID- 23853053
TI  - Parcellation of cerebellins 1, 2, and 4 among different subpopulations of dorsal
      horn neurons in mouse spinal cord.
AB  - The cerebellins (Cblns) are a family of secreted proteins that are widely
      expressed throughout the nervous system, but whose functions have been studied
      only in the cerebellum and striatum. Two members of the family, Cbln1 and Cbln2,
      bind to neurexins on presynaptic terminals and to GluRdeltas postsynaptically,
      forming trans-synaptic triads that promote synapse formation. Cbln1 has a higher
      binding affinity for GluRdeltas and exhibits greater synaptogenic activity than
      Cbln2. In contrast, Cbln4 does not form such triads and its function is unknown.
      The different properties of the three Cblns suggest that each plays a distinct
      role in synapse formation. To begin to elucidate Cbln function in other neuronal
      systems, we used in situ hybridization to examine Cbln expression in the mouse
      spinal cord. We find that neurons expressing Cblns 1, 2, and 4 tend to occupy
      different laminar positions within the dorsal spinal cord, and that Cbln
      expression is limited almost exclusively to excitatory neurons. Combined in situ
      hybridization and immunofluorescent staining shows that Cblns 1, 2, and 4 are
      expressed by largely distinct neuronal subpopulations, defined in part by sensory
      input, although there is some overlap and some individual neurons coexpress two
      Cblns. Our results suggest that differences in connectivity between
      subpopulations of dorsal spinal cord neurons may be influenced by which Cbln each
      subpopulation contains. Competitive interactions between axon terminals may
      determine the number of synapses each forms in any given region, and thereby
      contribute to the development of precise patterns of connectivity in the dorsal
      gray matter.

PMID- 23853055
TI  - Prostate cancer imaging trends after a nationwide effort to discourage
      inappropriate prostate cancer imaging.
AB  - BACKGROUND: Reducing inappropriate use of imaging to stage incident prostate
      cancer is a challenging problem highlighted recently as a Physician Quality
      Reporting System quality measure and by the American Society of Clinical Oncology
      and the American Urological Association in the Choosing Wisely campaign. Since
      2000, the National Prostate Cancer Register (NPCR) of Sweden has led an effort to
      decrease national rates of inappropriate prostate cancer imaging by disseminating
      utilization data along with the latest imaging guidelines to urologists in
      Sweden. We sought to determine the temporal and regional effects of this effort
      on prostate cancer imaging rates. METHODS: We performed a retrospective cohort
      study among men diagnosed with prostate cancer from the NPCR from 1998 to 2009 (n
      = 99 879). We analyzed imaging use over time stratified by clinical risk category
      (low, intermediate, high) and geographic region. Generalized linear models with a
      logit link were used to test for time trend. RESULTS: Thirty-six percent of men
      underwent imaging within 6 months of prostate cancer diagnosis. Overall, imaging
      use decreased over time, particularly in the low-risk category, among whom the
      imaging rate decreased from 45% to 3% (P < .001), but also in the high-risk
      category, among whom the rate decreased from 63% to 47% (P < .001). Despite
      substantial regional variation, all regions experienced clinically and
      statistically (P < .001) significant decreases in prostate cancer imaging.
      CONCLUSIONS: A Swedish effort to provide data on prostate cancer imaging use and
      imaging guidelines to clinicians was associated with a reduction in inappropriate
      imaging over a 10-year period, as well as slightly decreased appropriate imaging
      in high-risk patients. These results may inform current efforts to promote
      guideline-concordant imaging in the United States and internationally.

PMID- 23853056
TI  - Association between metformin use and risk of prostate cancer and its grade.
AB  - BACKGROUND: Metformin is commonly prescribed to treat type 2 diabetes. Recent
      evidence suggests that it may possess antitumoral properties. The aim of this
      study was to test the association between metformin use and risk of prostate
      cancer and its grade among men with diabetes. METHODS: Data were obtained from
      population-based health-care administrative databases in Ontario, Canada. This
      retrospective cohort study used a nested case-control approach to examine the
      relationship between metformin exposure and the risk of prostate cancer within a
      cohort of incident diabetic men aged 66 years or older. We conducted four case
      control analyses, defining case subjects as 1) any prostate cancer, 2) high
      grade, 3) low-grade, and 4) biopsy-diagnosed. In each analysis, case subjects
      were matched to five control subjects on age and cohort entry date. Metformin
      exposure was determined based on prescriptions before cancer diagnosis, and
      adjusted odds ratios (aOR) were estimated using conditional logistic regression.
      All statistical tests were two-sided. RESULTS: Within our cohort of 119 315 men
      with diabetes, there were 5306 case subjects with prostate cancer and 26 530
      matched control subjects. Within the cancer case subjects, 1104 had high- grade
      cancer, 1719 had low-grade cancer, and 3524 had biopsy-diagnosed cancer. There
      was no association between metformin use and risk of any prostate cancer (aOR =
      1.03, 95% confidence interval [CI] = 0.96 to 1.1), high-grade cancer (aOR = 1.13,
      95% CI = 0.96 to 1.32), low-grade cancer (aOR = 0.94, 95% CI = 0.82 to 1.06), or
      biopsy-diagnosed cancer (aOR = 0.98, 95% CI = 0.84 to 1.02). CONCLUSIONS: This
      large study did not find an association between metformin use and risk of
      prostate cancer among older men with diabetes, regardless of cancer grade or
      method of diagnosis.

PMID- 23853058
TI  - Increased osseointegration effect of bone morphogenetic protein 2 on dental
      implants: an in vivo study.
AB  - Application of recombinant human bone morphogenetic protein 2 (rhBMP-2) to
      implant surfaces has been of great interest due to its osteoinductive potential.
      However, the optimal coating methodology has not been clarified. The objective of
      the study was to determine whether the application of rhBMP-2 onto plasma-sprayed
      hydroxyapatite implant surfaces by immersion in protein solution before implant
      installation would result in significantly improved bone apposition. Using a
      sheep iliac model, titanium (Ti) and plasma-sprayed calcium-phosphate (PSCaP)
      coated implants uncoated and coated with rhBMP-2 were assessed for their
      osteogenic effects in the peri-implant area over time in terms of
      osseointegration and de novo bone formation. After 3 and 6 weeks postoperatively,
      the samples were retrieved and were subjected to bone-to-implant contact (BIC)
      and bone area fraction occupancy (BAFO) evaluation. When rhBMP-2 was applied to
      the PSCaP surface, significant increases in BIC and BAFO were observed at 3 weeks
      in vivo, whereas when adsorbed directly onto the titanium implant surface, rhBMP
      2 did not as effectively improve the bone response (although significantly higher
      than control Ti). The outcomes of the present study suggested that the
      combination of plasma-sprayed calcium-phosphate surface and rhBMP-2 coating
      significantly enhanced osseointegration, which validated the postulated
      hypothesis.

PMID- 23853059
TI  - Direct transformation of methyl imines to alpha-iminonitriles under mild and
      transition-metal-free conditions.
AB  - A novel transformation of methyl imines into alpha-iminonitriles under mild and
      transition-metal-free conditions is described. Three C sp 3-H bonds are cleaved
      in a radical pathway at room temperature under air. Simple bromide salts are
      employed to assist this radical process (see scheme; FG=functional group, PIDA =
      iodobenzene diacetate, TMS = trimethylsilyl).

PMID- 23853060
TI  - Retraction note to: Kearns Sayre Syndrome - case report with review of
      literature.

PMID- 23853061
TI  - Capacitance effects superimposed on redox processes in molecular-cluster
      batteries: a synergic route to high-capacity energy storage.
AB  - Rechargeable molecular-cluster batteries (MCBs) based on the manganese cluster
      complex [Mn12 O12 (CH3 CH2 C(CH3 )2 COO)16 (H2 O)4 ] ([Mn12]) that exhibited a
      capacity of approximately 200 A h kg(-1) in the battery voltage range of 4.0 to
      2.0 V were developed. In these batteries, the capacity of approximately 100 A h
      kg(-1) in the range of 4.0-3.0 V is caused by a chemical reduction from [Mn12](0)
      to [Mn12](8-) , whereas the other half in the range of 3.0-2.0 V cannot be
      explained by a redox change of the Mn ions. We performed the cyclic voltammetry
      (CV) and (7) Li solid-state NMR measurements on the Mn12-MCBs to investigate the
      origin of the capacity below 3.0 V. Pseudo-rectangular-shaped CV curves in the
      range of 3.0-2.0 V demonstrate the presence of an electrical double-layer (EDL)
      capacitance in Mn12-MCBs, which corresponds to approximately 100 A h kg(-1) . (7)
      Li NMR studies suggest that Li ions form an EDL with electrons in carbon black
      electrodes in the capacitance voltage range. The capacitance effects are not
      formed by the single-carbon electrodes alone, but appear only in the mixture of
      Mn12 and the carbon black electrodes. This type of coexistence of capacitance
      effects and redox reaction in one electrochemical cell is quite unusual and can
      serve as a new working principle for high-performance energy-storage devices. 

PMID- 23853057
TI  - Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a
      randomized, double-blind trial, N07C2.
AB  - BACKGROUND: Safe, effective interventions to improve cancer-related fatigue (CRF)
      are needed because it remains a prevalent, distressing, and activity-limiting
      symptom. Based on pilot data, a phase III trial was developed to evaluate the
      efficacy of American ginseng on CRF. METHODS: A multisite, double-blind trial
      randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo
      for 8 weeks. The primary endpoint was the general subscale of the
      Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at 4 weeks.
      Changes from baseline at 4 and 8 weeks were evaluated between arms by a two
      sided, two-sample t test. Toxicities were evaluated by self-report and the
      National Cancer Institute's Common Terminology Criteria for Adverse Events
      (CTCAE) provider grading. RESULTS: Three hundred sixty-four participants were
      enrolled from 40 institutions. Changes from baseline in the general subscale of
      the MFSI-SF were 14.4 (standard deviation [SD] = 27.1) in the ginseng arm vs 8.2
      (SD = 24.8) in the placebo arm at 4 weeks (P = .07). A statistically significant
      difference was seen at 8 weeks with a change score of 20 (SD = 27) for the
      ginseng group and 10.3 (SD = 26.1) for the placebo group (P = .003). Greater
      benefit was reported in patients receiving active cancer treatment vs those who
      had completed treatment. Toxicities per self-report and CTCAE grading did not
      differ statistically significantly between arms. CONCLUSIONS: Data support the
      benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There
      were no discernible toxicities associated with the treatment. Studies to increase
      knowledge to guide the role of ginseng to improve CRF are needed.

PMID- 23853062
TI  - DNA binding and bending by Sac7d is stepwise.
AB  - Which came first? Using thermodynamic cycles constructed from experimental
      measures of the binding free energy and free energy simulations, we have shown
      that binding of Sulfolobus acidocaldarius protein Sac7d to DNA occurs before DNA
      bending, thus indicating that a conformational selection mechanism is unlikely to
      be operative in Sac7d binding. 

PMID- 23853063
TI  - Exhaustively characterizing feasible logic models of a signaling network using
      Answer Set Programming.
AB  - MOTIVATION: Logic modeling is a useful tool to study signal transduction across
      multiple pathways. Logic models can be generated by training a network containing
      the prior knowledge to phospho-proteomics data. The training can be performed
      using stochastic optimization procedures, but these are unable to guarantee a
      global optima or to report the complete family of feasible models. This, however,
      is essential to provide precise insight in the mechanisms underlaying signal
      transduction and generate reliable predictions. RESULTS: We propose the use of
      Answer Set Programming to explore exhaustively the space of feasible logic
      models. Toward this end, we have developed caspo, an open-source Python package
      that provides a powerful platform to learn and characterize logic models by
      leveraging the rich modeling language and solving technologies of Answer Set
      Programming. We illustrate the usefulness of caspo by revisiting a model of pro
      growth and inflammatory pathways in liver cells. We show that, if experimental
      error is taken into account, there are thousands (11 700) of models compatible
      with the data. Despite the large number, we can extract structural features from
      the models, such as links that are always (or never) present or modules that
      appear in a mutual exclusive fashion. To further characterize this family of
      models, we investigate the input-output behavior of the models. We find 91
      behaviors across the 11 700 models and we suggest new experiments to discriminate
      among them. Our results underscore the importance of characterizing in a global
      and exhaustive manner the family of feasible models, with important implications
      for experimental design. AVAILABILITY: caspo is freely available for download
      (license GPLv3) and as a web service at http://caspo.genouest.org/. SUPPLEMENTARY
      INFORMATION: Supplementary materials are available at Bioinformatics online.
      CONTACT: santiago.videla@irisa.fr.

PMID- 23853064
TI  - RACER: Rapid and accurate correction of errors in reads.
AB  - MOTIVATION: High-throughput next-generation sequencing technologies enable
      increasingly fast and affordable sequencing of genomes and transcriptomes, with a
      broad range of applications. The quality of the sequencing data is crucial for
      all applications. A significant portion of the data produced contains errors, and
      ever more efficient error correction programs are needed. RESULTS: We propose
      RACER (Rapid and Accurate Correction of Errors in Reads), a new software program
      for correcting errors in sequencing data. RACER has better error-correcting
      performance than existing programs, is faster and requires less memory. To
      support our claims, we performed extensive comparison with the existing leading
      programs on a variety of real datasets. AVAILABILITY: RACER is freely available
      for non-commercial use at www.csd.uwo.ca/~ilie/RACER/.

PMID- 23853065
TI  - A siRNA system based on HSP70 promoter results in controllable and powerful gene
      silencing by heat-induction.
AB  - RNAi is a powerful tool for gene-specific knockdown and gene therapy. However,
      the imprecise expression of siRNA limits the extensive application of RNAi in
      gene therapy. Here we report the development of a novel controllable siRNA
      expression vector pMHSP70psil that is initiated by HSP70 promoter. We determined
      the efficiency of the controllable siRNA system by targeting the gama-synuclein
      (SNCG) gene in breast cancer cells MCF-7. The results show that the controllable
      siRNA system can be induced to initiate siRNA expression by heat-induction. The
      silencing effect of SNCG occurs at a relatively low level (10.1%) at 37 degrees
      C, while it is significantly increased to 69.4% after heat induction at 43
      degrees C. The results also show that the controllable siRNA system inhibits
      proliferation of cancer cells by heat-shock. Therefore, this RNAi strategy holds
      the promise of the high efficiency in gene knockdown at targeted times and
      locations, avoiding systemic side effects. It provides, for the first time, an
      approach to control siRNA expression by heat-shock.

PMID- 23853067
TI  - Physicians as teachers: are we ready for changing times?

PMID- 23853066
TI  - Bone morphogenetic protein-2, -6, and -7 differently regulate osteogenic
      differentiation of human periodontal ligament stem cells.
AB  - The utility of adult stem cells for bone regeneration may be an attractive
      alternative in the treatment of extensive injury, congenital malformations, or
      diseases causing large bone defects. To create an environment that is supportive
      of bone formation, signals from molecules such as the bone morphogenetic proteins
      (BMPs) are required to engineer fully viable and functional bone. We therefore
      determined whether BMP-2, -6, and -7 differentially regulate the (1)
      proliferation, (2) mineralization, and (3) mRNA expression of bone/mineralized
      tissue associated genes of human periodontal ligament stem cells (hPDLSCs), which
      were obtained from periodontal ligament tissue of human impacted third molars.
      hPDLSCs from six participants were isolated and characterized using histochemical
      and immunohistochemical methods. A real-time cell analyzer was used to evaluate
      the effects of BMP-2, -6, and -7 on the proliferation of hPDLSCs. hPDLSCs were
      treated with Dulbecco's modified Eagle's medium containing different
      concentrations of BMP-2, -6, and -7 (10, 25, 50, 100 ng/mL) and monitored for 264
      hours. After dose-response experiments, 50 and 100 ng/mL concentrations of BMPs
      were used to measure bone/mineralized tissue-associated gene expression. Type I
      collagen, bone sialoprotein, osteocalcin, osteopontin, and osteoblastic
      transcription factor Runx2 mRNA expression of hPDLSCs treated with BMP-2, -6, and
      -7, were evaluated using quantitative RT-PCR. Biomineralization of hPDLSCs was
      assessed using von Kossa staining. This study demonstrated that BMPs at various
      concentrations differently regulate the proliferation, mineralization, and mRNA
      expression of bone/mineralized tissue associated genes in hPDLSCs. BMPs regulate
      hPDLSC proliferation in a time and dose-dependent manner when compared to an
      untreated control group. BMPs induced bone/mineralized tissue-associated gene
      mRNA expression and biomineralization of hPDLSCs. The most pronounced induction
      occurred in the BMP-6 group in the biomineralization of the hPDLSCs. Our data
      suggest that BMP-2, -6, and -7 are potent regulators of hPDLSC gene expression
      and biomineralization. Employing BMPs with hPDLSCs isolated from periodontal
      ligament tissues provides a promising strategy for bone tissue engineering.

PMID- 23853068
TI  - A de novo SCA14 mutation in an isolated case of late-onset cerebellar ataxia.

PMID- 23853070
TI  - Self-assembly structures of 1H-indazoles in the solution and solid phases: a
      vibrational (IR, FIR, Raman, and VCD) spectroscopy and computational study.
AB  - 1H-indazoles are good candidates for studying the phenomena of molecular
      association and spontaneous resolution of chiral compounds. Thus, because the 1H
      indazoles can crystallize as dimers, trimers, or catemers, depending on their
      structure and the phase that they are in, the difficulty in the experimental
      analysis of the structure of the family of 1H-indazoles becomes clear. This
      difficulty leads us to contemplate several questions: How can we determine the
      presence of different structures of a given molecular species if they change
      according to the phase? Could these different structures be present in the same
      phase simultaneously? How can they be determined? To shed light on these
      questions, we outline a very complete strategy by using various vibrational
      spectroscopic techniques that are sensitive (VCD) and insensitive (IR, FIR, and
      Raman) towards the chirality, together with quantum chemical calculations. 

PMID- 23853071
TI  - [1,1-Co2(CO)6(CNAr Mes 2)2]: a structural mimic of the elusive D2d isomer of
      [Co2(CO)8].

PMID- 23853069
TI  - Considerations in binding diblock copolymers on hydrophilic alginate beads for
      providing an immunoprotective membrane.
AB  - Alginate-based microcapsules are being proposed for treatment of many types of
      diseases. A major obstacle however in the successes is that these capsules are
      having large lab-to-lab variations. To make the process more reproducible, we
      propose to cover the surface of alginate capsules with diblock polymers that can
      form polymer brushes. In the present study, we describe the stepwise
      considerations for successful application of diblock copolymer of polyethylene
      glycol (PEG) and poly-L-lysine (PLL) on the surface of alginate beads. Special
      procedures had to be designed as alginate beads are hydrophilic and most
      protocols are designed for hydrophobic biomaterials. The successful attachment of
      diblock copolymer and the presence of PEG blocks on the surface of the capsules
      were studied by fluorescence microscopy. Longer time periods, that is, 30-60 min,
      are required to achieve saturation of the surface. The block lengths influenced
      the strength of the capsules. Shorter PLL blocks resulted in less stable
      capsules. Adequate permeability of the capsules was achieved with poly(ethylene
      glycol)-block-poly(L-lysine hydrochloride) (PEG454-b-PLL100) diblock copolymers.
      The capsules were a barrier for immunoglobulin G. The PEG454-b-PLL100 capsules
      have similar mechanical properties as PLL capsules. Minor immune activation of
      nuclear factor kappaB in THP-1 monocytes was observed with both PLL and PEG454-b
      PLL100 capsules prepared from purified alginate. Our results show that we can
      successfully apply block copolymers on the surface of hydrophilic alginate beads
      without interfering with the physicochemical properties.

PMID- 23853073
TI  - Interactions of the heart and the liver.
AB  - There is a mutual interaction between the function of the heart and the liver and
      a broad spectrum of acute and chronic entities that affect both the heart and the
      liver. These can be classified into heart diseases affecting the liver, liver
      diseases affecting the heart, and conditions affecting the heart and the liver at
      the same time. In chronic and acute cardiac hepatopathy, owing to cardiac
      failure, a combination of reduced arterial perfusion and passive congestion leads
      to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may
      impair the liver function and treatment should be directed towards the primary
      heart disease and seek to secure perfusion of vital organs. In patients with
      advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced
      cardiac performance with systolic and diastolic dysfunction and electrophysical
      abnormalities termed cirrhotic cardiomyopathy. Electrophysiological abnormalities
      include prolonged QT interval, chronotropic incompetance, and electromechanical
      uncoupling. No specific therapy can be recommended, but it should be supportive
      and directed against the heart failure. Numerous conditions affect both the heart
      and the liver such as infections, inflammatory and systemic diseases, and chronic
      alcoholism. The risk and prevalence of coronary artery disease are increasing in
      cirrhotic patients and since the perioperative mortality is high, a careful
      cardiac evaluation of such patients is required prior to orthotopic liver
      transplantation.

PMID- 23853072
TI  - Impact of ageing on presentation and outcome of mitral regurgitation due to flail
      leaflet: a multicentre international study.
AB  - AIMS: Define the impact of age at diagnosis on degenerative mitral regurgitation
      (MR) prognosis. METHODS AND RESULTS: The Mitral regurgitation International
      DAtabase (MIDA) is a multicentre registry of MR due to flail leaflets including
      862 patients (65 +/- 12 years) diagnosed by echocardiography. The 498 older
      patients (>=65 years at diagnosis) were compared with the 364 younger (<65) with
      regard to presentation and the outcome was compared with that expected in the
      general population. Older vs. younger patients had MR of similar severity and
      ventricular overload but presented with more MR consequences and incurred higher
      mortality [risk ratio (rr) 95% confidence interval (95% CI) 4.7 (2.5-10.0), P <
      0.001] independently of co-morbidity. Compared with expected survival [relative
      risk (95% confidence interval)], excess mortality, non-significant in younger
      patients [1.1 (0.6-2.0), P = 0.65], was prominent in older patients [1.4 (1.2
      1.7), P < 0.001]. Compared with expected, excess heart failure (HF) occurred in
      younger [9.3 (6.5-13.3), P < 0.0001) and in older patients [6.7 (5.6-8.1), P <
      0.0001]. Excess atrial fibrillation (AF) was even higher in younger [6.9 (4.5
      10.6), P < 0.0001] than in older patients [3.5 (2.6-4.7), P < 0.0001; P < 0.001
      for comparison between age groups]. Subsequent excess mortality [rr (95% CI)] was
      associated with occurrence of HF and/or AF in both age groups [13.5 (7.4-24.6), P
      < 0.001]. Mitral surgery was associated with reduced long-term mortality in older
      patients and lower rate of HF in both the age groups (all P < 0.01). CONCLUSIONS:
      Both older and younger patients incurred excess risk of complications. Older
      patients suffered excess mortality, AF, and HF, whereas younger incurred excess
      morbidity linked to subsequent long-term excess mortality. The excess risks of
      uncorrected degenerative MR should be considered in deliberating surgical
      management, which significantly reduced mortality in older patients and HF in
      younger patients.

PMID- 23853074
TI  - A genome-wide association study identifies 6p21 as novel risk locus for dilated
      cardiomyopathy.
AB  - AIMS: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac
      transplantations and accounts for up to one-third of all heart failure cases.
      Since extrinsic and monogenic causes explain only a fraction of all cases, common
      genetic variants are suspected to contribute to the pathogenesis of DCM, its age
      of onset, and clinical progression. By a large-scale case-control genome-wide
      association study we aimed here to identify novel genetic risk loci for DCM.
      METHODS AND RESULTS: Applying a three-staged study design, we analysed more than
      4100 DCM cases and 7600 controls. We identified and successfully replicated
      multiple single nucleotide polymorphism on chromosome 6p21. In the combined
      analysis, the most significant association signal was obtained for rs9262636 (P =
      4.90 * 10(-9)) located in HCG22, which could again be replicated in an
      independent cohort. Taking advantage of expression quantitative trait loci (eQTL)
      as molecular phenotypes, we identified rs9262636 as an eQTL for several closely
      located genes encoding class I and class II major histocompatibility complex
      heavy chain receptors. CONCLUSION: The present study reveals a novel genetic
      susceptibility locus that clearly underlines the role of genetically driven,
      inflammatory processes in the pathogenesis of idiopathic DCM.

PMID- 23853075
TI  - Chemical shift assignment of the ataxin-1 AXH domain in complex with a CIC ligand
      peptide.
AB  - Ataxin-1 is the protein responsible for the genetically-inherited
      neurodegenerative disease spinocerebellar ataxia type-1 linked to the expansion
      of a polyglutamine tract within the protein sequence. The AXH domain of ataxin-1
      is essential for the protein to function as a transcriptional co-repressor and
      mediates the majority of the interactions of ataxin-1 with cellular partners,
      mainly transcriptional regulators. One of the best characterized ataxin-1
      functional partners is Capicua (CIC), a transcriptional repressor involved in
      signalling pathways that regulate mammalian development, tumorigenesis and,
      through the interaction with ataxin-1, also neurodegeneration. Complex formation
      of ataxin-1 with CIC is important both for the function of the wild-type protein
      and for pathogenesis as transcriptional disregulation is observed since the early
      stages of the development of the disease. Here we report the (1)H, (13)C and
      (15)N backbone and side-chain chemical shift assignments of the human ataxin-1
      AXH domain in complex with a CIC ligand-peptide. 

PMID- 23853076
TI  - Backbone 1H, 13C and 15N assignments of YibK and avariant containing a unique
      cysteine residue at C-terminus in 8 M urea-denatured states [corrected].
AB  - YibK is a tRNA methyltransferase from Haemophilus influenzae, which forms a
      stable homodimer in solution and contains a deep trefoil 31 knot encompassing the
      C-terminal helix that threads through a long loop. It has been a model system for
      investigating knotted protein folding pathways. Recent data have shown that the
      polypeptide chain of YibK remains loosely knotted under highly denaturing
      conditions. Here, we report (1)H, (13)C and (15)N chemical shift assignments for
      YibK and its variant in the presence of 8 M urea. This work forms the basis for
      further analysis using NMR techniques such as paramagnetic relaxation
      enhancement, residual dipolar couplings and spin-relaxation dynamics analysis.

PMID- 23853077
TI  - Two whisker motor areas in the rat cortex: evidence from thalamocortical
      connections.
AB  - In primates, the motor cortex consists of at least seven different areas, which
      are involved in movement planning, coordination, initiation, and execution.
      However, for rats, only the primary motor cortex has been well described. A
      rostrally located second motor area has been proposed, but its extent,
      organization, and even definitive existence remain uncertain. Only a rostral
      forelimb area (RFA) has been definitively described, besides few reports of a
      rostral hindlimb area. We have previously proposed existence of a second whisker
      area, which we termed the rostral whisker area (RWA), based on its differential
      response to intracortical microstimulation compared with the caudal whisker area
      (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci
      27:228). To establish that RWA is distinct from the caudally contiguous CWA, we
      determined sources of thalamic inputs to the two proposed whisker areas. Sources
      of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were
      determined for comparison. The results show that RWA and CWA can be distinguished
      based on differences in their thalamic inputs. RWA receives major projections
      from mediodorsal and ventromedial nuclei, whereas the major projections to CWA
      are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the
      thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the
      nuclei projecting to CWA are same as for CFA. The results suggest that rats have
      a second rostrally located motor area with RWA and RFA as its constituents.

PMID- 23853078
TI  - Genotype imputation in genome-wide association studies.
AB  - Imputation is an in silico method that can increase the power of association
      studies by inferring missing genotypes, harmonizing data sets for meta-analyses,
      and increasing the overall number of markers available for association testing.
      This unit provides an introductory overview of the imputation method and
      describes a two-step imputation approach that consists of the phasing of the
      study genotypes and the imputation of reference panel genotypes into the study
      haplotypes. Detailed steps for data preparation and quality control illustrate
      how to run the computationally intensive two-step imputation with the high
      density reference panels of the 1000 Genomes Project, which currently integrates
      more than 39 million variants. Additionally, the influence of reference panel
      selection, input marker density, and imputation settings on imputation quality
      are demonstrated with a simulated data set to give insight into crucial points of
      successful genotype imputation.

PMID- 23853080
TI  - Oncolytic adenoviruses: design, generation, and experimental procedures.
AB  - Oncolytic adenoviruses are designed to take advantage of the virus' native
      ability to replicate in cancer cells to induce oncolysis. Subsequently, the
      released viral progeny spread and kill the neighboring cancer cells. These
      characteristics, together with the ability of adenovirus to infect a broad
      spectrum of cells, its well understood replication machinery, and relative ease
      of manufacture have led to the intensive use of adenovirus as an anticancer
      agent. This unit describes cloning strategies, procedures to turn the intended
      design into virus, and quality analyses of resultant adenoviral vectors. Most of
      these procedures were optimized especially for oncolytic adenoviral vectors.

PMID- 23853079
TI  - Identifying rare variants associated with complex traits via sequencing.
AB  - Although genome-wide association studies have been successful in detecting
      associations with common variants, there is currently an increasing interest in
      identifying low-frequency and rare variants associated with complex traits. Next
      generation sequencing technologies make it feasible to survey the full spectrum
      of genetic variation in coding regions or the entire genome. The association
      analysis for rare variants is challenging, and traditional methods are
      ineffective, however, due to the low frequency of rare variants, coupled with
      allelic heterogeneity. Recently a battery of new statistical methods has been
      proposed for identifying rare variants associated with complex traits. These
      methods test for associations by aggregating multiple rare variants across a gene
      or a genomic region or among a group of variants in the genome. In this unit, we
      describe key concepts for rare variant association for complex traits, survey
      some of the recent methods, discuss their statistical power under various
      scenarios, and provide practical guidance on analyzing next-generation sequencing
      data for identifying rare variants associated with complex traits.

PMID- 23853082
TI  - Single nucleotide polymorphism genotyping using BeadChip microarrays.
AB  - The genotyping of single nucleotide polymorphisms (SNPs) has successfully
      contributed to the study of complex diseases more than any other technology to
      date. Genome-wide association studies (GWAS) using 10,000s to >1,000,000 SNPs
      have identified 1000s of statistically significant SNPs pertaining to 17
      different human disease and trait categories. Post-GWAS fine-mapping studies
      using 10,000s to 100,000s SNPs on a microarray have narrowed the region of
      interest for many of these GWAS findings; in addition, independent signals within
      the original GWAS region have been identified. Focused content, SNP-based
      microarrays such as the human exome, for example, have too been used successfully
      to identify novel disease associations. Success has come to studies where 100s to
      10,000s (mostly) to >100,000 samples were genotyped. For the time being, SNP
      based microarrays remain cost-effective especially when studying large numbers of
      samples compared to other "genotyping" technologies including next generation
      sequencing. In this unit, protocols for manual (LIMS-free), semi-manual, and
      automated processing of BeadChip microarrays are presented. Lower throughput
      studies will find value in the manual and semi-manual protocols, while all types
      of studies--low-, medium-, and high-throughput--will find value in the semi
      manual and automated protocols.

PMID- 23853083
TI  - A silyliumylidene cation stabilized by an amidinate ligand and 4
      dimethylaminopyridine.
AB  - The synthesis and reactivity of a silyliumylidene cation stabilized by an
      amidinate ligand and 4-dimethylaminopyridine (DMAP) are described. The reaction
      of the amidinate silicon(I) dimer [LSi:]2 (1; L = PhC(NtBu)2) with one equivalent
      of N-trimethylsilyl-4-dimethylaminopyridinium triflate [4-NMe2C5H4NSiMe3]OTf and
      two equivalents of DMAP in THF afforded [LSi(DMAP)]OTf (2). The ambiphilic
      character of 2 is demonstrated from its reactivity. Treatment of 2 with 1 in THF
      afforded the disilylenylsilylium triflate [L'2(L)Si]OTf (3; L' = LSi:) with the
      displacement of DMAP. The reaction of 2 with [K{HB(iBu)3}] and elemental sulfur
      in THF afforded the silylsilylene [LSiSi(H){(NtBu)2C(H)Ph}] (4) and the base
      stabilized silanethionium triflate [LSi(S)DMAP]OTf (5), respectively. Compounds
      2, 3, and 5 have been characterized by X-ray crystallography.

PMID- 23853081
TI  - Gene delivery to the airway.
AB  - This unit describes generation of and gene transfer to several commonly used
      airway models. Isolation and transduction of primary airway epithelial cells are
      first described. Next, the preparation of polarized airway epithelial monolayers
      is outlined. Transduction of these polarized cells is also described. Methods are
      presented for generation of tracheal xenografts, as well as both ex vivo and in
      vivo gene transfer to these xenografts. Finally, a method for in vivo gene
      delivery to the lungs of rodents is included. Methods for evaluating transgene
      expression are given in the support protocols.

PMID- 23853084
TI  - Left ventricular non-compaction presenting with heart failure and intramural
      thrombus.
AB  - Left ventricular non-compaction (LVNC) is a rare disorder caused by the arrest of
      myocardial compaction during embryogenesis, leading to a non-compacted
      endocardial layer with marked trabeculations. The diagnosis is primarily based on
      echocardiographic demonstration of a spongy myocardium. Here, we present a young
      male with LVNC presenting with left heart failure and multiple left ventricular
      thrombi. We also review the presentation, diagnosis and management of this
      condition. 

PMID- 23853085
TI  - New development of cardiac tamponade on underlying effusive-constrictive
      pericarditis: an uncommon initial presentation of scleroderma.
AB  - A 40-year-old man with a medical history of hypertension was admitted for weight
      loss, generalised weakness, joint pains and mottling of fingertips. The initial
      laboratory data revealed microangiopathic haemolytic anaemia, thrombocytopenia
      and acute renal failure. Intravenous steroids were started for possible diagnosis
      of systemic lupus erythematosus based on admission assessment. Intravenous
      immunoglobulin and plasmapharesis were subsequently added to the treatment plan
      to cover thrombotic thrombocytopenic purpura while his autoimmune panel was
      pending. The echocardiogram study on day 2 revealed cardiac tamponade for which
      he underwent pericardiocentesis and right heart catheterisation. The atrial
      waveforms postpericardiocentesis demonstrated effusive-constrictive pericarditis.
      His clinical condition kept on deteriorating with reaccumulation of pericardial
      effusion and further complicated by hemoperitoneum and colonic obstruction. He
      had cardiorespiratory arrest on his fourth admission day and was not revived.
      Anti-Scl-70 antibody came back positive. Autopsy findings confirmed the presence
      of fibrinous pericarditis and hemoperitoneum. 

PMID- 23853086
TI  - Reflex gelastic-dacrystic seizures following hypoxic-ischaemic encephalopathy.
AB  - Reflex or stimulus-sensitive epilepsies are uncommon epileptic syndromes
      triggered by exogenous-specific sensory stimulus or endogenous various mental
      activities. Gelastic-dacrystic seizures are rare epileptic manifestations
      characterised by ictal laughter and crying. Gelastic-dacrystic seizures are
      commonly caused by hypothalamic hamartoma but rarely described due to cortical
      dysplasia, lesions of frontal and temporal lobes, tumours and vascular
      malformations. We report a young woman who presented with somatosensory-evoked
      gelastic-dacrystic seizures. This patient had a positive history of perinatal
      insult substantiated by MRI findings. Hypoxic-ischaemic encephalopathy as the
      cause of gelastic-dacrystic seizures has not been reported so far in the
      literature. 

PMID- 23853087
TI  - Wild-type, Flemish, and Dutch amyloid-beta exhibit different cytotoxicities
      depending on Abeta40 to Abeta42 interaction time and concentration ratio.
AB  - Addition of amyloid beta (Abeta) peptide Abeta40 to Abeta42 can delay Abeta42
      aggregation, but consequent cytotoxicity has been reported to be enhanced or
      diminished. In the present study, we found that cytotoxicity was enhanced when
      human neuroblastoma SH-SY5Y cells were incubated in a mixture of wt Abeta42 and
      Abeta40wt at a ratio of 1 : 10-20 (0.1 : 1-2 MUM) for 24-36 h, whereas the
      enhancement was detected in cells incubated for longer times (48-60 h) with the
      less amyloidogenic Flemish Abeta40 variant or in cells incubated for as short as
      12 h with the more amyloidogenic Dutch variant. Reductions in cytotoxicity by
      Abeta40 were most prominently observed in the Flemish and wt Abeta40/Abeta42
      mixture at ratio 1 : 20 incubated for a short time (~12 h). The most cytotoxic
      Abeta40/Abeta42 mixtures were enriched in Abeta protofibril-like structures,
      implying a strong correlation between cytotoxicity and this structure, the
      formation of which was dependent on amyloidogenic properties and incubation time.
      The consequences of the interactions were probably because of the different
      amyloidogenic properties of the Abeta40 variants, rather than to those of
      Abeta42, because aggregation rates of Abeta40 variants were highly dependent on
      sequence, whereas those of Abeta42 variants were not. These studies highlight a
      potential role for Abeta40 in cytotoxicity and provide novel mechanistic insights
      into the pathogenesis of each familial Alzheimer's disease-associated Abeta40
      variant.

PMID- 23853088
TI  - The importance of standard operating procedures in clinical trials.
AB  - This special contribution provides insight into the role that standard operating
      procedures (SOPs) play in an imaging department and their value in building a
      high-quality research site. If you have ever participated in a clinical trial,
      many of the principles described in this article should be familiar. However,
      this article goes a step further by presenting information from a pharmaceutical
      or device sponsor's point of view-what the sponsor expects from a site during the
      course of a research study. This article is intended not to provide a complete
      set of instructions on how to create a great SOP but, instead, to present
      guidelines to ensure that the key elements are included. After reading the
      article, you will be able to define SOPs as they pertain to the clinical trial
      environment, describe key components of an SOP, list the clinical research SOPs
      that exist in your institution and imaging department, identify which additional
      SOPs might improve site performance, and describe how the sponsor relies on SOPs
      to ensure that the highest quality of research is attained. 

PMID- 23853089
TI  - Pallidal stimulation for cervical dystonia does not correct abnormal temporal
      discrimination.
AB  - BACKGROUND: We investigated whether clinical improvement observed after deep
      brain stimulation (DBS) of the globus pallidus internus (GPi) in cervical
      dystonia (CD) is paralleled by the normalisation of temporal discrimination
      thresholds (TDTs), a marker of abnormal sensory processing in CD. METHODS: TDT
      was tested in 11 patients with CD after they received DBS and was compared with
      TDT scores from 24 patients with CD and a group of 61 controls. RESULTS: A clear
      clinical response to GPi-DBS was demonstrated (total Toronto Western Spasmodic
      Torticollis Rating Scale scores fell from 50 to 18; P < 0.001). In contrast, TDT
      remained abnormal in the CD-DBS group (P < 0.001) and was not significantly
      different from the abnormal TDT range observed in CD. CONCLUSIONS: Underlying
      sensory abnormalities in temporal discrimination observed in dystonia do not seem
      to be corrected by successful GPi-DBS. This adds further data to the ongoing
      debate regarding which pathophysiological abnormalities observed in dystonia are
      likely to be causal in the genesis of the disease rather than epiphenomena
      observed secondary to abnormal motor activity.

PMID- 23853090
TI  - Sequence diversity in coding regions of candidate genes in the glycoalkaloid
      biosynthetic pathway of wild potato species.
AB  - Natural variation in five candidate genes of the steroidal glycoalkaloid (SGA)
      metabolic pathway and whole-genome single nucleotide polymorphism (SNP)
      genotyping were studied in six wild [Solanum chacoense (chc 80-1), S.
      commersonii, S. demissum, S. sparsipilum, S. spegazzinii, S. stoloniferum] and
      cultivated S. tuberosum Group Phureja (phu DH) potato species with contrasting
      levels of SGAs. Amplicons were sequenced for five candidate genes: 3-hydroxy-3
      methylglutaryl coenzyme A reductase 1 and 2 (HMG1, HMG2) and 2.3-squalene
      epoxidase (SQE) of primary metabolism, and solanidine galactosyltransferase
      (SGT1), and glucosyltransferase (SGT2) of secondary metabolism. SNPs (n = 337)
      producing 354 variations were detected within 3.7 kb of sequenced DNA. More
      polymorphisms were found in introns than exons and in genes of secondary compared
      to primary metabolism. Although no significant deviation from neutrality was
      found, dN/dS ratios < 1 and negative values of Tajima's D test suggested
      purifying selection and genetic hitchhiking in the gene fragments. In addition,
      patterns of dN/dS ratios across the SGA pathway suggested constraint by natural
      selection. Comparison of nucleotide diversity estimates and dN/dS ratios showed
      stronger selective constraints for genes of primary rather than secondary
      metabolism. SNPs (n = 24) with an exclusive genotype for either phu DH (low SGA)
      or chc 80-1 (high SGA) were identified for HMG2, SQE, SGT1 and SGT2. The SolCAP
      8303 Illumina Potato SNP chip genotyping revealed eight informative SNPs on six
      pseudochromosomes, with homozygous and heterozygous genotypes that discriminated
      high, intermediate and low levels of SGA accumulation. These results can be used
      to evaluate SGA accumulation in segregating or association mapping populations. 

PMID- 23853091
TI  - Mitochondrial DNA with a large-scale deletion causes two distinct mitochondrial
      disease phenotypes in mice.
AB  - Studies in patients have suggested that the clinical phenotypes of some
      mitochondrial diseases might transit from one disease to another (e.g., Pearson
      syndrome [PS] to Kearns-Sayre syndrome) in single individuals carrying
      mitochondrial (mt) DNA with a common deletion (DeltamtDNA), but there is no
      direct experimental evidence for this. To determine whether DeltamtDNA has the
      pathologic potential to induce multiple mitochondrial disease phenotypes, we used
      trans-mitochondrial mice with a heteroplasmic state of wild-type mtDNA and
      DeltamtDNA (mito-miceDelta). Late-stage embryos carrying >=50% DeltamtDNA showed
      abnormal hematopoiesis and iron metabolism in livers that were partly similar to
      PS (PS-like phenotypes), although they did not express sideroblastic anemia that
      is a typical symptom of PS. More than half of the neonates with PS-like
      phenotypes died by 1 month after birth, whereas the rest showed a decrease of
      DeltamtDNA load in the affected tissues, peripheral blood and liver, and they
      recovered from PS-like phenotypes. The proportion of DeltamtDNA in various
      tissues of the surviving mito-miceDelta increased with time, and Kearns-Sayre
      syndrome-like phenotypes were expressed when the proportion of mtDNA in various
      tissues reached >70-80%. Our model mouse study clearly showed that a single
      DeltamtDNA was responsible for at least two distinct disease phenotypes at
      different ages and suggested that the level and dynamics of mtDNA load in
      affected tissues would be important for the onset and transition of mitochondrial
      disease phenotypes in mice.

PMID- 23853092
TI  - Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory
      gene expression in macrophages.
AB  - Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like
      receptor (TLR)-inducible production of key proinflammatory mediators. Here we
      investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the
      classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory
      macrophages (thioglycollate-elicited peritoneal macrophages) as compared with
      bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a
      specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino
      acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible
      expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A
      novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme
      activity as well as TLR-induced production of inflammatory mediators in
      thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated
      the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A
      hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for
      HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1alpha
      mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u
      and Hdac7-s interacted with HIF-1alpha, whereas only Hdac7-s interacted with the
      transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1alpha
      dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely
      prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential
      inflammatory disease target. 

PMID- 23853094
TI  - Foxp3 protein stability is regulated by cyclin-dependent kinase 2.
AB  - Foxp3 is a transcription factor required for the development of regulatory T
      cells (Treg). Mice and humans with a loss of Foxp3 function suffer from
      uncontrolled autoimmunity and inflammatory disease. Expression of Foxp3 is
      necessary for the anti-inflammatory capacity of Treg, but whether Foxp3 activity
      is further subject to regulation by extracellular signals is unclear. The primary
      structure of Foxp3 contains four cyclin-dependent kinase (CDK) motifs (Ser/Thr
      Pro) within the N-terminal repressor domain, and we show that CDK2 can partner
      with cyclin E to phosphorylate Foxp3 at these sites. Consistent with our previous
      demonstration that CDK2 negatively regulates Treg function, we find that mutation
      of the serine or threonine at each CDK motif to alanine (S/T->A) results in
      enhanced Foxp3 protein stability in CD4(+) T cells. T cells expressing the S/T->A
      mutant of Foxp3 showed enhanced induction (e.g. CD25) and repression (e.g. IL2)
      of canonical Foxp3-responsive genes, exhibited an increased capacity to suppress
      conventional T cell proliferation in vitro, and were highly effective at
      ameliorating colitis in an in vivo model of inflammatory bowel disease. These
      results indicate that CDK2 negatively regulates the stability and activity of
      Foxp3 and implicate CDK-coupled receptor signal transduction in the control of
      regulatory T cell function and stability. 

PMID- 23853093
TI  - Proto-oncogene activity of melanoma antigen-A11 (MAGE-A11) regulates
      retinoblastoma-related p107 and E2F1 proteins.
AB  - Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid
      receptor coregulator in normal tissues of the human reproductive tract that is
      expressed at higher levels in prostate cancer. Increased expression of MAGE-A11
      enhances androgen receptor transcriptional activity and promotes prostate cancer
      cell growth. Further investigation into the mechanisms of MAGE-A11 function in
      prostate cancer demonstrated interactions with the retinoblastoma-related protein
      p107 and Rb tumor suppressor but no interaction with p130 of the Rb family. MAGE
      A11 interaction with p107 was associated with transcriptional repression in cells
      with low MAGE-A11 and transcriptional activation in cells with higher MAGE-A11.
      Selective interaction of MAGE-A11 with retinoblastoma family members suggested
      the regulation of E2F transcription factors. MAGE-A11 stabilized p107 by
      inhibition of ubiquitination and linked p107 to hypophosphorylated E2F1 in
      association with the stabilization and activation of E2F1. The androgen receptor
      and MAGE-A11 modulated endogenous expression of the E2F1-regulated cyclin
      dependent kinase inhibitor p27(Kip1). The ability of MAGE-A11 to increase E2F1
      transcriptional activity was similar to the activity of adenovirus early
      oncoprotein E1A and depended on MAGE-A11 interactions with p107 and p300. The
      immunoreactivity of p107 and MAGE-A11 was greater in advanced prostate cancer
      than in benign prostate, and knockdown with small inhibitory RNA showed that p107
      is a transcriptional activator in prostate cancer cells. These results suggest
      that MAGE-A11 is a proto-oncogene whose increased expression in prostate cancer
      reverses retinoblastoma-related protein p107 from a transcriptional repressor to
      a transcriptional activator of the androgen receptor and E2F1. 

PMID- 23853095
TI  - Per-Arnt-Sim kinase regulates pancreatic duodenal homeobox-1 protein stability
      via phosphorylation of glycogen synthase kinase 3beta in pancreatic beta-cells.
AB  - In pancreatic beta-cells, glucose induces the binding of the transcription factor
      pancreatic duodenal homeobox-1 (PDX-1) to the insulin gene promoter to activate
      insulin gene transcription. At low glucose levels, glycogen synthase kinase 3beta
      (GSK3beta) is known to phosphorylate PDX-1 on C-terminal serine residues, which
      triggers PDX-1 proteasomal degradation. We previously showed that the
      serine/threonine Per-Arnt-Sim domain-containing kinase (PASK) regulates insulin
      gene transcription via PDX-1. However, the mechanisms underlying this regulation
      are unknown. In this study, we aimed to identify the role of PASK in the
      regulation of PDX-1 phosphorylation, protein expression, and stability in insulin
      secreting cells and isolated rodent islets of Langerhans. We observed that
      glucose induces a decrease in overall PDX-1 serine phosphorylation and that
      overexpression of WT PASK mimics this effect. In vitro, PASK directly
      phosphorylates GSK3beta on its inactivating phosphorylation site Ser(9).
      Overexpression of a kinase-dead (KD), dominant negative version of PASK blocks
      glucose-induced Ser(9) phosphorylation of GSK3beta. Accordingly, GSK3beta Ser(9)
      phosphorylation is reduced in islets from pask-null mice. Overexpression of WT
      PASK or KD GSK3beta protects PDX-1 from degradation and results in increased PDX
      1 protein abundance. Conversely, overexpression of KD PASK blocks glucose
      induction of PDX-1 protein. We conclude that PASK phosphorylates and inactivates
      GSK3beta, thereby preventing PDX-1 serine phosphorylation and alleviating
      GSK3beta-mediated PDX-1 protein degradation in pancreatic beta-cells. 

PMID- 23853096
TI  - ADP-ribosylation of translation elongation factor 2 by diphtheria toxin in yeast
      inhibits translation and cell separation.
AB  - Eukaryotic translation elongation factor 2 (eEF2) facilitates the movement of the
      peptidyl tRNA-mRNA complex from the A site of the ribosome to the P site during
      protein synthesis. ADP-ribosylation (ADP(R)) of eEF2 by bacterial toxins on a
      unique diphthamide residue inhibits its translocation activity, but the mechanism
      is unclear. We have employed a hormone-inducible diphtheria toxin (DT) expression
      system in Saccharomyces cerevisiae which allows for the rapid induction of ADP(R)
      eEF2 to examine the effects of DT in vivo. ADP(R) of eEF2 resulted in a decrease
      in total protein synthesis consistent with a defect in translation elongation.
      Association of eEF2 with polyribosomes, however, was unchanged upon expression of
      DT. Upon prolonged exposure to DT, cells with an abnormal morphology and
      increased DNA content accumulated. This observation was specific to DT expression
      and was not observed when translation elongation was inhibited by other methods.
      Examination of these cells by electron microscopy indicated a defect in cell
      separation following mitosis. These results suggest that expression of proteins
      late in the cell cycle is particularly sensitive to inhibition by ADP(R)-eEF2. 

PMID- 23853097
TI  - Structural insights into the neutralization mechanism of monoclonal antibody 6C2
      against ricin.
AB  - Ricin belongs to the type II ribosome-inactivating proteins that depurinate the
      universally conserved alpha-sarcin loop of rRNA. The RNA N-glycosidase activity
      of ricin also largely depends on the ribosomal proteins that play an important
      role during the process of rRNA depurination. Therefore, the study of the
      interaction between ricin and the ribosomal elements will be better to understand
      the catalysis mechanism of ricin. The antibody 6C2 is a mouse monoclonal antibody
      exhibiting unusually potent neutralizing ability against ricin, but the
      neutralization mechanism remains unknown. Here, we report the 2.8 A crystal
      structure of 6C2 Fab in complex with the A-chain of ricin (RTA), which reveals an
      extensive antigen-antibody interface that contains both hydrogen bonds and van
      der Waals contacts. The complementarity-determining region loops H1, H2, H3, and
      L3 form a pocket to accommodate the epitope on the RTA (residues Asp(96)
      Thr(116)). ELISA results show that Gln(98), Glu(99), Glu(102), and Thr(105) (RTA)
      are the key residues that play an important role in recognizing 6C2. With the
      perturbation of the 6C2 Fab-RTA interface, 6C2 loses its neutralization ability,
      measured based on the inhibition of protein synthesis in a cell-free system.
      Finally, we propose that the neutralization mechanism of 6C2 against ricin is
      that the binding of 6C2 hinders the interaction between RTA and the ribosome and
      the surface plasmon resonance and pulldown results confirm our hypothesis. In
      short, our data explain the neutralization mechanism of mAb 6C2 against ricin and
      provide a structural basis for the development of improved antibody drugs with
      better specificity and higher affinity. 

PMID- 23853099
TI  - MinC protein shortens FtsZ protofilaments by preferentially interacting with GDP
      bound subunits.
AB  - The interaction of MinC with FtsZ and its effects on FtsZ polymerization were
      studied under close to physiological conditions by a combination of biophysical
      methods. The Min system is a widely conserved mechanism in bacteria that ensures
      the correct placement of the division machinery at midcell. MinC is the component
      of this system that effectively interacts with FtsZ and inhibits the formation of
      the Z-ring. Here we report that MinC produces a concentration-dependent reduction
      in the size of GTP-induced FtsZ protofilaments (FtsZ-GTP) as demonstrated by
      analytical ultracentrifugation, dynamic light scattering, fluorescence
      correlation spectroscopy, and electron microscopy. Our experiments show that,
      despite being shorter, FtsZ protofilaments maintain their narrow distribution in
      size in the presence of MinC. The protein had the same effect regardless of its
      addition prior to or after FtsZ polymerization. Fluorescence anisotropy
      measurements indicated that MinC bound to FtsZ-GDP with a moderate affinity
      (apparent KD ~10 MUM at 100 mm KCl and pH 7.5) very close to the MinC
      concentration corresponding to the midpoint of the inhibition of FtsZ assembly.
      Only marginal binding of MinC to FtsZ-GTP protofilaments was observed by
      analytical ultracentrifugation and fluorescence correlation spectroscopy.
      Remarkably, MinC effects on FtsZ-GTP protofilaments and binding affinity to FtsZ
      GDP were strongly dependent on ionic strength, being severely reduced at 500 mM
      KCl compared with 100 mM KCl. Our results support a mechanism in which MinC
      interacts with FtsZ-GDP, resulting in smaller protofilaments of defined size and
      having the same effect on both preassembled and growing FtsZ protofilaments.

PMID- 23853098
TI  - MicroRNA-124 suppresses the transactivation of nuclear factor of activated T
      cells by targeting multiple genes and inhibits the proliferation of pulmonary
      artery smooth muscle cells.
AB  - Abnormal proliferation and phenotypic modulation of pulmonary artery smooth
      muscle cells (PASMC) contributes to the pathogenesis of numerous cardiovascular
      disorders, including pulmonary arterial hypertension (PAH). The nuclear factor of
      activated T cells (NFAT) signaling pathway is linked to PASMC proliferation and
      PAH. MicroRNAs (miRNAs) are small non-coding RNAs that function in diverse
      biological processes. To systemically identify the specific miRNAs that regulate
      the NFAT pathway, a human primary miRNA library was applied for cell-based high
      throughput screening with the NFAT luciferase reporter system. Eight miRNAs were
      found to modulate NFAT activity efficiently. Of them, miR-124 robustly inhibited
      NFAT reporter activity and decreased both the dephosphorylation and the nuclear
      translocation of NFAT. miR-124 also inhibited NFAT-dependent transcription of IL
      2 in Jurkat T cells. miR-124 exerted its effects by targeting multiple genes,
      including a known component of the NFAT pathway, NFATc1, and two new regulators
      of NFAT signaling, CAMTA1 (calmodulin-binding transcription activator 1) and
      PTBP1 (polypyrimidine tract-binding protein 1). Physiologically, miR-124 was down
      regulated by hypoxia in human PASMC, consistent with the activation of NFAT
      during this process. Down-regulation of miR-124 was also observed in 3-week
      hypoxia-treated mouse lungs. Furthermore, the overexpression of miR-124 not only
      inhibited human PASMC proliferation but also maintained its differentiated
      phenotype by repressing the NFAT pathway. Taken together, our data provide the
      first evidence that miR-124 acts as an inhibitor of the NFAT pathway. Down
      regulation of miR-124 in hypoxia-treated PASMC and its antiproliferative and
      prodifferentiation effects imply a potential value for miR-124 in the treatment
      of PAH. 

PMID- 23853100
TI  - Effects of crosslinked dextran in hydroxylpropyl methylcellulose on soft tissue
      augmentation in rats.
AB  - This study compared crosslinked dextrans in hydroxylpropyl methycellulose (DiHMs,
      pH 5 or 7) with polymethylmethacrylate in bovine collagen (PMMA) and hyaluronic
      acid (HA) fillers on soft tissue augmentation and safety in rats. HA tended to
      maintain its size throughout the experimental period but was moveable and friable
      because of a lack of thick fibroconnective tissue formation. Although, PMMA
      induced moderately thick fibroconnective tissue formation, its size was decreased
      markedly from 3-week postimplantation (PI) and became the smallest at 24-month
      PI. DiHM (pH 7) elicited strong fibrous encapsulation around the filler. Its size
      decreased slowly but was still considerably maintained at 24-month PI. In
      contrast, the rate of the DiHM (pH 5) size decrease was slower than that of PMMA,
      faster DiHM (pH 7), but comparable to HA. Immunohistochemically, types I and III
      collagens were deposited inside and outside DiHMs (pH 5 and 7). DiHMs (pH 5 and
      7), PMMA, and HA showed no adverse reactions. These results suggest that DiHM (pH
      7) assures efficacy and safety and is a good candidate for soft tissue
      augmentation in both humans and animals.

PMID- 23853101
TI  - Microstructural effects on the wear behavior of a biomedical as-cast Co-27Cr-5Mo
      0.25C alloy exposed to pulsed laser melting.
AB  - In this work, the effect of pulsed laser melting on the exhibited microstructure
      and properties of a cast Co-27Cr-5Mo-0.25C alloy was investigated. In particular,
      properties such as surface hardness and wear behavior of the laser modified
      microstructure were determined as a function of the implemented laser melting
      parameters. It was found that laser melting promotes significant grain refinement
      while preventing the precipitation of coarse carbide phases. Apparently, a
      refined dendritic grain structure develops which is surrounded by a fine carbide
      distribution in the interdendritic regions. Moreover, the high-temperature face
      centered cubic (FCC) phase remains untransformed at room temperature. Hardness
      measurements and wear testing using a Pin-On-Disk tribological machine indicate
      that the modified laser surfaces exhibit both, high wear resistance and high
      microhardness when compared with the untreated as-cast Co-27Cr-5Mo-0.25C alloy.
      In particular, it was found that the laser modified surfaces exhibit improved
      wear and friction properties comparable to the ones found in Co-Cr-Mo alloys with
      a predominantly hexagonal closest packed (HCP) matrix. However, surface defects
      associated with the laser process can be detrimental for the improved wear
      performance and they should be considered in identifying the proper laser
      parameters in alloy melting.

PMID- 23853102
TI  - More than meets the eye: conformational switching of a stacked
      dialkoxynaphthalene-naphthalenetetracarboxylic diimide (DAN-NDI) foldamer to an
      NDI-NDI fibril aggregate.
AB  - The thermally induced conformational switching of a stacked dialkxoynaphthalene
      naphthalenetetracarboxylic diimide (DAN-NDI) amphiphilic foldamer to an NDI-NDI
      fibril aggregate is described. The aggregated fibril structures were explored by
      UV/Vis, circular dichroism (CD), atomic-force microscopy (AFM), and TEM
      techniques. Our findings indicate that the aromatic DAN-NDI interactions of the
      original foldamer undergoes transformation to a fibrillar assembly with aromatic
      NDI-NDI stacked interactions. These structural insights could help inform new
      molecular designs and increase our understanding of fibrillar assembly and
      aggregation process in aqueous solution. 

PMID- 23853103
TI  - Proposal for generating new beta cells in a muted immune environment for type 1
      diabetes.
AB  - BACKGROUND: Over the past decade, many immune tolerance agents have shown promise
      in the non-obese diabetic mouse model for prevention and reversal of type 1
      diabetes but have not been successful in clinical trials among recently diagnosed
      type 1 patients. The trials from decades ago using Cyclosporine A in
      significantly lower dosages than used for organ transplantation and in similar
      dosages that have increased T regulatory cell populations in conditions such as
      atopic dermatitis, demonstrated very high initial insulin-free remission rates
      when administered immediately after diagnosis. Over time, all newly diagnosed
      type 1 patients given Cyclosporine A required insulin. Human trials with immune
      tolerance agents suggest that in addition to an immune tolerance agent, a beta
      cell regeneration agent may also be necessary to induce long-lasting remission
      among patients with recent onset type 1 diabetes. METHODS: A randomized, double
      blind prospective trial among recent onset type 1 diabetes patients has been
      designed using Cyclosporine A and a proton-pump inhibitor, which increases
      gastrin levels and has been shown to work through the Reg receptor to transform
      pancreatic duct cells into islets.

PMID- 23853105
TI  - Fluorescent hydroxylamine derived from the fragmentation of PAMAM dendrimers for
      intracellular hypochlorite recognition.
AB  - Herein, a promising sensing approach based on the structure fragmentation of
      poly(amidoamine) (PAMAM) dendrimers for the selective detection of intracellular
      hypochlorite (OCl(-)) is reported. PAMAM dendrimers were easily disrupted by a
      cascade of oxidations in the tertiary amines of the dendritic core to produce an
      unsaturated hydroxylamine with blue fluorescence. Specially, the novel
      fluorophore was only sensitive to OCl(-), one of reactive oxygen species (ROS),
      resulting in an irreversible fluorescence turn-off. The fluorescent hydroxylamine
      was selectively oxidised by OCl(-) to form a labile oxoammonium cation that
      underwent further degradation. Without using any troublesomely synthetic steps,
      the novel sensing platform based on the fragmentation of PAMAM dendrimers, can be
      applied to detect OCl(-) in macrophage cells. The results suggest that the
      sensing approach may be useful for the detection of intracellular OCl(-) with
      minimal interference from biological matrixes.

PMID- 23853104
TI  - Depletion of the transcriptional coactivators megakaryoblastic leukaemia 1 and 2
      abolishes hepatocellular carcinoma xenograft growth by inducing oncogene-induced
      senescence.
AB  - Megakaryoblastic leukaemia 1 and 2 (MKL1/2) are coactivators of the transcription
      factor serum response factor (SRF). Here, we provide evidence that depletion of
      MKL1 and 2 abolishes hepatocellular carcinoma (HCC) xenograft growth. Loss of the
      tumour suppressor deleted in liver cancer 1 (DLC1) and the subsequent activation
      of RhoA were prerequisites for MKL1/2 knockdown-mediated growth arrest. We
      identified oncogene-induced senescence as the molecular mechanism underlying the
      anti-proliferative effect of MKL1/2 knockdown. MKL1/2 depletion resulted in Ras
      activation, elevated p16 expression and hypophosphorylation of the retinoblastoma
      (Rb) protein in DLC1-deficient HCC cells. Interestingly, reconstitution of HuH7
      HCC cells with DLC1 also induced senescence. Evaluation of the therapeutic
      efficacy of MKL1/2 knockdown in vivo revealed that systemic treatment of nude
      mice bearing HuH7 tumour xenografts with MKL1/2 siRNAs complexed with
      polyethylenimine (PEI) completely abolished tumour growth. The regression of the
      xenografts was associated with senescence. Importantly, PEI-complexed MKL1 siRNA
      alone was sufficient for complete abrogation of HCC xenograft growth. Thus,
      MKL1/2 represent promising novel therapeutic targets for the treatment of HCCs
      characterized by DLC1 loss. 

PMID- 23853106
TI  - Psychosocial and lifestyle correlates of musculoskeletal pain patterns in
      adolescence: a 2-year follow-up study.
AB  - BACKGROUND: The prevalence of musculoskeletal (MS) pain has been increasing among
      adolescents in the last decades. This may be related to either adverse changes in
      lifestyle and/or the psychosocial environment. Our study analysed the
      psychosocial and lifestyle correlates of musculoskeletal pain progression in
      adolescence. METHODS: The study was based on the 1986 Northern Finland Birth
      Cohort and included 1773 adolescents at the ages of 16 to 18. Latent class
      analysis was applied to find the homogeneous profiles of MS pains in four body
      areas (neck, shoulder, low back and limb). We analysed the associations between
      time spent in sedentary activities and sleeping, physical activity level, body
      mass index, alcohol consumption, smoking, and emotional and behavioural factors
      at 16 years, and belonging to pain clusters at 16 and 18 years. RESULTS: We found
      an association between a higher probability of MS pains between 16 and 18 years
      and increasing emotional and behavioural problems in both genders. Among boys, a
      high likelihood of MS pains during follow-up was also associated with a long time
      spent sitting and insufficient sleeping time. Among girls, alcohol consumption
      associated with high pain probability. MS pains already co-occur to a large
      extent in their early course. CONCLUSIONS: The strong overlap of emotional and
      behavioural problems and MS pains in adolescence requires awareness in both
      research and clinical work.

PMID- 23853107
TI  - Analysis of genome-wide association study-linked loci in Parkinson's disease of
      Mainland China.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified numerous
      single-nucleotide polymorphisms (SNPs) that can modulate the risk of developing
      Parkinson's disease (PD). METHODS: We investigated the association of previously
      identified loci in a Mainland Chinese population to identify a possible ethnic
      specific effect with GWAS analysis. Seventeen SNPs were genotyped from those loci
      using case-control methodology to analyze a total of 1,737 individuals. RESULTS:
      Strong evidence of an association for reference SNP 894278 (rs894278) and
      rs11931074 on 4q22 throughout the alpha synuclein (SNCA) region was observed in
      our study. The SNP rs894278 confers risk via a dominant model and an additive
      model, whereas the minor allele G of rs11931074 reduces the risk of PD
      progression. The minor allele frequency of rs11724635 produced weaker signals for
      PD, but this was not replicated in the genotype after adjusting for age and sex.
      CONCLUSIONS: This study yields new clues about GWAS-linked data in patients with
      PD from Mainland China.

PMID- 23853109
TI  - Assembly of synapses: biomimetic assays to control neurexin/neuroligin
      interactions at the neuronal surface.
AB  - The role of adhesion molecules in the assembly of synapses in the nervous system
      is an important issue. To characterize the role of neurexin/neuroligin adhesion
      complexes in synapse differentiation, various imaging assays can be performed in
      primary hippocampal cultures. First, to temporally control contact formation,
      biomimetic assays can be performed using microspheres coated with purified
      neurexin or with antibody clusters that aggregate neurexin. These models are
      combined with live fluorescence imaging to study the dynamics of accumulation of
      post-synaptic components, including scaffolding molecules and glutamate
      receptors. To demonstrate that AMPA receptors can be recruited to nascent
      neurexin/neuroligin contacts through lateral diffusion, the mobility of AMPA
      receptors in the neuronal membrane is monitored by tracking individual quantum
      dots (QDs) conjugated to antibodies against AMPA receptors. Experiments
      monitoring the attachment and detachment of Nrx-coated QDs to measure the rates
      of neurexin/neuroligin interaction can also be performed. Each of these assays is
      detailed in this unit.

PMID- 23853110
TI  - Incubation of fear.
AB  - While fear and anxiety can grow over time in anxiety disorders, most efforts to
      model this phenomenon with fear conditioning in rodents cause fear that remains
      stable or decreases across weeks or months. Here, we describe several methods to
      induce conditioned fear that grows over the course of 1 month and is sustained
      for at least 2 months using an extended fear conditioning approach. These methods
      include a very reliable standard method that causes multiple fear measures to
      increase over months, as well as alternative methods.

PMID- 23853111
TI  - A choice-based screening method for compulsive drug users in rats.
AB  - We describe a protocol for screening compulsive drug users among cocaine self
      administering rats, the most frequently used animal model in addiction research.
      Rats are first trained on several alternating days to self-administer either
      cocaine (i.v.) or saccharin-sweetened water (by mouth)--a potent, albeit
      nonessential, nondrug reward. Then rats are allowed to choose between the two
      rewards over several days until the preference stabilizes. Most rats choose to
      stop using cocaine and pursue the alternative reward. Only a minority of Wistar
      strain rats (generally 15%) persist in taking the drug, regardless of the
      severity of past cocaine use and even when made hungry and offered the
      possibility to relieve their physiological need. Persistence of cocaine use in
      the face of a high-stakes choice is a core defining feature of compulsion. This
      choice-based screening method for compulsive drug users is easy to implement, has
      several important applications, and compares well with other methods in the
      field.

PMID- 23853108
TI  - Topographically organized projection to posterior insular cortex from the
      posterior portion of the ventral medial nucleus in the long-tailed macaque
      monkey.
AB  - Prior anterograde tracing work identified somatotopically organized lamina I
      trigemino- and spinothalamic terminations in a cytoarchitectonically distinct
      portion of posterolateral thalamus of the macaque monkey, named the posterior
      part of the ventral medial nucleus (VMpo; Craig [2004] J. Comp. Neurol. 477:119
      148). Microelectrode recordings from clusters of selectively thermoreceptive or
      nociceptive neurons were used to guide precise microinjections of various tracers
      in VMpo. A prior report (Craig and Zhang [2006] J. Comp. Neurol. 499:953-964)
      described retrograde tracing results, which confirmed the selective lamina I
      input to VMpo and the anteroposterior (head to foot) topography. The present
      report describes the results of microinjections of anterograde tracers placed at
      different levels in VMpo, based on the anteroposterior topographic organization
      of selectively nociceptive units and clusters over nearly the entire extent of
      VMpo. Each injection produced dense, patchy terminal labeling in a single
      coherent field within a distinct granular cortical area centered in the fundus of
      the superior limiting sulcus. The terminations were distributed with a consistent
      anteroposterior topography over the posterior half of the superior limiting
      sulcus. These observations demonstrate a specific VMpo projection area in dorsal
      posterior insular cortex that provides the basis for a somatotopic representation
      of selectively nociceptive lamina I spinothalamic activity. These results also
      identify the VMpo terminal area as the posterior half of interoceptive cortex;
      the anterior half receives input from the vagal-responsive and gustatory neurons
      in the basal part of the ventral medial nucleus.

PMID- 23853112
TI  - Animal models of post-traumatic stress disorder.
AB  - Animal behavioral studies have commonly regarded the entire group of animals
      subjected to the study conditions as homogeneous, disregarding individual
      differences in response patterns. The following discussion will focus on a method
      of analyzing data that aims to model clinical diagnostic criteria applied to
      individual patterns of response using data from behavioral measures, and
      employing cut-off scores to distinguish between extremes of response versus non
      response and the sizeable proportion of study subjects in-between them. This
      protocol unit will present the concept of the model and its background, provide
      detailed protocols for each of its components, and present a selection of studies
      employing and examining the model, alongside the underlying translational
      rationale of each.

PMID- 23853113
TI  - Titaniumcarboxonitride layer increased biocompatibility of medical
      polyetherurethanes.
AB  - Polyetherurethane (PEU) is in use for blood-contacted devices because of its
      excellent mechanical properties. However, poor hemocompatibility of the
      hydrophobic material required surface modification or endothelialization. To
      increase the biocompatibility of PEU, the polymer was coated with a
      titaniumcarboxonitride [Ti(C,N,O)] layer by a plasma-activated chemical vapor
      deposition (PACVD) process. Biocompatibility of titaniferously coated PEU was
      verified using static and dynamic cell culture techniques. Titaniferous coating
      significantly improved proliferation and mitochondrial activity of human
      endothelial cells on PEU. These cells captured significantly less mononuclear
      cells and platelets. Under shear stress for up to 72 hours, titaniferous coating
      increased endothelial cell adhesion, spreading, and cell density to form an
      organized monolayer covering the whole luminal surface of vascular PEU grafts. In
      summary, coating of PEU surfaces with Ti(C,N,O) might be a promising strategy to
      improve the biocompatibility of biomedical biomaterials.

PMID- 23853114
TI  - Sericin-carboxymethyl cellulose porous matrices as cellular wound dressing
      material.
AB  - In this study, porous three-dimensional (3D) hydrogel matrices are fabricated
      composed of silk cocoon protein sericin of non-mulberry silkworm Antheraea
      mylitta and carboxymethyl cellulose. The matrices are prepared via freeze-drying
      technique followed by dual cross-linking with glutaraldehyde and aluminum
      chloride. The microstructure of the hydrogel matrices is assessed using scanning
      electron microscopy and biophysical characterization are carried out using
      Fourier transform infrared spectroscopy and X-ray diffraction. The transforming
      growth factor beta1 release from the cross-linked matrices as a growth factor is
      evaluated by immunosorbent assay. Live dead assay and 3-[4,5-dimethylthiazolyl-2]
      2,5-diphenyl tetrazolium bromide assay show no cytotoxicity of blended matrices
      toward human keratinocytes. The matrices support the cell attachment and
      proliferation of human keratinocytes as observed through scanning electron
      microscope and confocal images. Gelatin zymography demonstrates the low levels of
      matrix metalloproteinase 2 (MMP-2) and insignificant amount of MMP-9 in the
      culture media of cell seeded matrices. Low inflammatory response of the matrices
      is indicated through tumor necrosis factor alpha release assay. The results
      indicate that the fabricated matrices constitute 3D cell-interactive environment
      for tissue engineering applications and its potential use as a future cellular
      biological wound dressing material.

PMID- 23853115
TI  - Interaction of E2F7 transcription factor with E2F1 and C-terminal-binding protein
      (CtBP) provides a mechanism for E2F7-dependent transcription repression.
AB  - Previous work has identified distinct functions for E2F proteins during a
      cellular proliferative response including a role for E2F1-3 in the activation of
      transcription at G1/S and a role for E2F4-8 in repressing the same group of E2F1
      3 target genes as cells progress through S phase. We now find that E2F7 and E2F8,
      which are induced by E2F1-3 at G1/S, can form a heterodimer with E2F1 through
      interactions involving the DNA-binding domains of the two proteins. In vitro DNA
      interaction assays demonstrate the formation of an E2F1-E2F7 complex, as well as
      an E2F7-E2F7 complex on adjacent E2F-binding sites. We also show that E2F7
      recruits the co-repressor C-terminal-binding protein (CtBP) and that CtBP2 is
      essential for E2F7 to repress E2F1 transcription. Taken together, these findings
      suggest a mechanism for the repression of transcription by E2F7. 

PMID- 23853116
TI  - Formation and geometrical control of polygon-like metal-coordination assemblies.
AB  - Polygon-like [2+2]- and [3+3]-type metal complexes were prepared from dipyrrin
      dimers connected by acute-angled spacers. The electrical conduction depends
      strongly on the packing alignment of the compounds, revealing the presence of
      effective hopping pathways for holes with relatively high mobility up to 0.11
      cm(2)  V(-1)  s(-1) along the aligned axis of [3+3]-type metal-bridged
      assemblies. These observations correlated with the geometrical control of the pi
      conjugated metal complexes in the cyclic structures, which enables their ordered
      arrangement in the assemblies. 

PMID- 23853117
TI  - VEGF-A regulated by progesterone governs uterine angiogenesis and vascular
      remodelling during pregnancy.
AB  - The features and regulation of uterine angiogenesis and vascular remodelling
      during pregnancy are poorly defined. Here we show that dynamic and variable
      decidual angiogenesis (sprouting, intussusception and networking), and active
      vigorous vascular remodelling such as enlargement and elongation of 'vascular
      sinus folding' (VSF) and mural cell drop-out occur distinctly in a spatiotemporal
      manner in the rapidly growing mouse uterus during early pregnancy - just after
      implantation but before placentation. Decidual angiogenesis is mainly regulated
      through VEGF-A secreted from the progesterone receptor (PR)-expressing decidual
      stromal cells which are largely distributed in the anti-mesometrial region (AMR).
      In comparison, P4 -PR-regulated VEGF-A-VEGFR2 signalling, ligand-independent
      VEGFR3 signalling and uterine natural killer (uNK) cells positively and
      coordinately regulate enlargement and elongation of VSF. During the postpartum
      period, Tie2 signalling could be involved in vascular maturation at the
      endometrium in a ligand-independent manner, with marked reduction of VEGF-A,
      VEGFR2 and PR expressions. Overall, we show that two key vascular growth factor
      receptors - VEGFR2 and Tie2 - strikingly but differentially regulate decidual
      angiogenesis and vascular remodelling in rapidly growing and regressing uteri in
      an organotypic manner. 

PMID- 23853119
TI  - Burrowing as a non-reflex behavioural readout for analgesic action in a rat model
      of sub-chronic knee joint inflammation.
AB  - BACKGROUND: Innate responses against spontaneous pain are proposed to improve the
      predictive validity of preclinical analgesia models. Therefore, development and
      validation of novel readouts is necessary. To investigate whether innate rodent
      burrowing is a useful alternative behavioural readout for assessment of analgesic
      efficacy, a complete Freund's adjuvant (CFA)-induced model of sub-chronic
      inflammation was used to compare the effects of naproxen, ibuprofen and
      pregabalin in weight-bearing (WB), open-field (OF) and burrowing assays. METHODS:
      Male Sprague Dawley rats were injected with 150 MUL of CFA (2 mg/mL) into the
      knee (hind leg) 3 days before testing. Naproxen, ibuprofen and pregabalin were
      administered at different doses 30, 90 and 60 min, respectively, before testing.
      WB was determined using a rat incapacitance tester; horizontal distance moved and
      vertical rearings were recorded in an OF; and burrowing was measured by the
      weight of gravel remaining in a hollow tube after 60 min. RESULTS: CFA-induced
      arthritis reduced WB, OF activity and burrowing. Naproxen, pregabalin and
      ibuprofen treatment normalized WB; however, horizontal OF activity was not
      improved by any treatment; rearing behaviour was moderately reinstated by
      ibuprofen (100 mg/kg). In burrowing, naproxen (100 mg/kg), ibuprofen (31.6 and
      100 mg/kg) and pregabalin (10 mg/kg) reversed CFA-induced deficits. CONCLUSIONS:
      Burrowing performance is an alternative non-reflex readout relying on innate
      rodent behaviour that is affected by nociceptive behaviour and can be
      pharmacologically manipulated. The burrowing assay appears to be more sensitive
      than OF assays and is as sensitive as WB assays at distinguishing between
      analgesic doses and doses that impair locomotion.

PMID- 23853120
TI  - Synthesis, characterization, and antiplasmodial activity of polymer-incorporated
      aminoquinolines.
AB  - In this research, aminoquinoline compounds were synthesized, characterized, and
      incorporated into water-soluble polymers to form conjugates. The conjugates were
      characterized by X-ray diffraction, thermal gravimetric analysis, scanning
      electron microscope, Fourier transform infrared spectroscopy, and nuclear
      magnetic resonance spectroscopy to confirm the successful incorporation of the
      aminoquinoline compound on to the polymer. The synthesized conjugates were
      screened for in vitro antiplasmodial activity in triplet test against chloroquine
      sensitive strain of Plasmodium falciparum and chloroquine drug was used as a
      reference drug in all the experiments. A full dose-response was performed to
      determine the concentration inhibiting 50% of parasite growth (IC50 value).
      Polymeric conjugates containing 3-diethylamino-1-propylamine solubilizing units
      were found to be most active against the chloroquine-sensitive strain of P.
      falciparum.

PMID- 23853118
TI  - Corticocortical projections to representations of the teeth, tongue, and face in
      somatosensory area 3b of macaques.
AB  - We placed injections of anatomical tracers into representations of the tongue,
      teeth, and face in the primary somatosensory cortex (area 3b) of macaque monkeys.
      Our injections revealed strong projections to representations of the tongue and
      teeth from other parts of the oral cavity responsive region in 3b. The 3b face
      also provided input to the representations of the intraoral structures. The
      primary representation of the face showed a pattern of intrinsic connections
      similar to that of the mouth. The area 3b hand representation provided little to
      no input to either the mouth or the face representations. The mouth and face
      representations of area 3b received projections from the presumptive oral cavity
      and face regions of other somatosensory areas in the anterior parietal cortex and
      the lateral sulcus, including areas 3a, 1, 2, the second somatosensory area (S2),
      the parietal ventral area (PV), and cortex that may include the parietal rostral
      (PR) and ventral somatosensory (VS) areas. Additional inputs came from primary
      motor (M1) and ventral premotor (PMv) areas. This areal pattern of projections is
      similar to the well-studied pattern revealed by tracer injections in regions of
      3b representing the hand. The tongue representation appeared to be unique in area
      3b in that it also received inputs from areas in the anterior upper bank of the
      lateral sulcus and anterior insula that may include the primary gustatory area
      (area G) and other cortical taste-processing areas, as well as a region of
      lateral prefrontal cortex (LPFC) lining the principal sulcus.

PMID- 23853122
TI  - Nanosciences at NCNST: from fundamental research to industrial applications.

PMID- 23853124
TI  - Tumor fibroblast specific activation of a hybrid ferritin nanocage-based optical
      probe for tumor microenvironment imaging.
AB  - Ferritin-based FAP-alpha-responsive fluorescence nanoprobes could be activated
      immediately as they penetrate the tumor blood vessels and come across the FAP
      alpha molecules on the membrane of CAFs in the tumor microenvironment instead of
      reaching a certain depth into tumor tissue to interact with tumor cells. This
      probe may become a promising nanomaterial for highly specific and sensitive tumor
      imaging through responding to the enzymes in the tumor microenvironment. 

PMID- 23853121
TI  - Breaking the take home pesticide exposure pathway for agricultural families:
      workplace predictors of residential contamination.
AB  - BACKGROUND: Pesticides used in agriculture can be taken into worker homes and
      pose a potential risk for children and other family members. This study focused
      on identification of potential intervention points at the workplace. METHODS:
      Workers (N = 46) recruited from two tree fruit orchards in Washington State were
      administered a 63-item pesticide safety questionnaire. Dust was collected from
      commuter vehicles and worker homes and analyzed for four organophosphorus (OP)
      pesticides (azinphosmethyl, phosmet, chlorpyrifos, malathion). RESULTS: Geometric
      mean azinphosmethyl concentrations in dust for three worker groups (16 pesticide
      handlers, 15 green fruit thinners, 15 organic orchard workers) ranged from 0.027
      1.5 MUg/g, with levels in vehicle dust higher than in house dust, and levels in
      house dust from handlers' homes higher than levels from tree fruit thinners'
      homes. Vehicle and house dust concentrations of azinphosmethyl were highly
      associated (R(2) = 0.44, P < 0.001). Significant differences were found across
      worker groups for availability of laundry facilities, work boot storage,
      frequency of hand washing, commuter vehicle use, parking location, and safety
      training. CONCLUSIONS: These findings support a focus on intervention activities
      to reduce take home pesticide exposure closer to the source of contamination;
      specifically, the workplace and vehicles used to travel to the workplace.

PMID- 23853125
TI  - High mechanical performance of layered graphene oxide/poly(vinyl alcohol)
      nanocomposite films.
AB  - The design and fabrication of strong, lightweight, and damage-resistant composite
      materials are major topics of studies on composites. Biomimetics, a developing
      multidisciplinary field, is now leading the fabrication of novel materials with
      remarkable mechanical properties. Graphene oxide (GO), a graphene derivative,
      possesses good mechanical properties, a high aspect ratio, and good solubility in
      aqueous solutions, indicating great potential in nanocomposite fields. In this
      work, bioinspired layered GO/poly(vinyl alcohol) (PVA) nanocomposite films with
      remarkable mechanical performances are prepared by an environmental friendly,
      bottom-up assembly methodology. The structural analysis shows alternate piles of
      inorganic GO platelets and organic PVA binder. Tensile tests indicate that the
      borate-treated GO/PVA nanocomposite films display 360 MPa of strength, which is
      twofold to threefold higher than that of biological materials (e.g., nacre).
      Toughness of GO/PVA nanocomposites is also enhanced fourfold compared with nacre.
      To reveal the toughening function of the intercalated polymer in the
      nanocomposites, the influence of polymer with varied molecular weights (Mws) on
      the fracture mode of the nanocomposites is systematically investigated through
      quasi-static tensile and creep tests. The PVA molecules with a higher Mw can
      connect more neighboring GO platelets through inter- and intra-linkages than
      those with a lower Mw, resulting in efficient stress transfer along the GO plane
      direction. Thus, tensile strength and toughness are improved. This work
      illustrates the functions of bonding types between inorganic-organic phases and
      intercalated polymers with different Mws on the mechanical properties of the
      layered nanocomposites, including stiffness, strength, and toughness. 

PMID- 23853126
TI  - An endoperoxide-based hybrid approach to deliver falcipain inhibitors inside
      malaria parasites.
AB  - The emergence of artemisinin-resistant Plasmodium falciparum malaria in Southeast
      Asia has reinforced the urgent need to discover novel chemotherapeutic strategies
      to treat and control malaria. To address this problem, we prepared a set of dual
      acting tetraoxane-based hybrid molecules designed to deliver a falcipain-2 (FP-2)
      inhibitor upon activation by iron(II) in the parasite digestive vacuole. These
      hybrids are active in the low nanomolar range against chloroquine-sensitive and
      chloroquine-resistant P. falciparum strains. We also demonstrate that in the
      presence of FeBr2 or within infected red blood cells, these molecules fragment to
      release falcipain inhibitors with nanomolar protease inhibitory activity.
      Molecular docking studies were performed to better understand the molecular
      interactions established between the tetraoxane-based hybrids and the cysteine
      protease binding pocket residues. Our results further indicate that the intrinsic
      activity of the tetraoxane partner compound can be masked, suggesting that a
      tetraoxane-based delivery system offers the potential to attenuate the off-target
      effects of known drugs.

PMID- 23853127
TI  - In vitro protein binding of liraglutide in human plasma determined by reiterated
      stepwise equilibrium dialysis.
AB  - Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue approved for the
      treatment of type 2 diabetes. It is based on human GLP-1 with the addition of a
      16-carbon fatty acid, which facilitates binding to plasma proteins, thus
      prolonging the elimination half-life and allowing once-daily administration. It
      has not been possible to quantify liraglutide protein binding by ultrafiltration
      (the usual method of choice), as the lipophilic molecule becomes trapped in the
      filter membrane. Therefore, the aim of this study was to develop a methodology
      that could determine the extent of liraglutide binding to plasma proteins in
      vitro. We report here the details of a novel reiterated stepwise equilibrium
      dialysis assay that has successfully been used to quantify liraglutide plasma
      protein binding. The assay allowed quantification of liraglutide binding to
      proteins in purified plasma protein solutions and human plasma samples and was
      effective at plasma dilutions as low as 5%. At a clinically relevant liraglutide
      concentration (10(4) pM), greater than 98.9% of liraglutide was bound to protein.
      Specific binding to human serum albumin and alpha1-acid glycoprotein was 99.4%
      and 99.3%, respectively. The novel methodology described herein could have an
      application in the quantification of plasma protein binding of other highly
      lipophilic drug molecules.

PMID- 23853128
TI  - Energy efficient medium access protocol for wireless medical body area sensor
      networks.
AB  - This paper presents a novel energy-efficient MAC Protocol designed specifically
      for wireless body area sensor networks (WBASN) focused towards pervasive
      healthcare applications. Wireless body area networks consist of wireless sensor
      nodes attached to the human body to monitor vital signs such as body temperature,
      activity or heart-rate. The network adopts a master-slave architecture, where the
      body-worn slave node periodically sends sensor readings to a central master node.
      Unlike traditional peer-to-peer wireless sensor networks, the nodes in this
      biomedical WBASN are not deployed in an ad hoc fashion. Joining a network is
      centrally managed and all communications are single-hop. To reduce energy
      consumption, all the sensor nodes are in standby or sleep mode until the
      centrally assigned time slot. Once a node has joined a network, there is no
      possibility of collision within a cluster as all communication is initiated by
      the central node and is addressed uniquely to a slave node. To avoid collisions
      with nearby transmitters, a clear channel assessment algorithm based on standard
      listen-before-transmit (LBT) is used. To handle time slot overlaps, the novel
      concept of a wakeup fallback time is introduced. Using single-hop communication
      and centrally controlled sleep/wakeup times leads to significant energy
      reductions for this application compared to more ldquoflexiblerdquo network MAC
      protocols such as 802.11 or Zigbee. As duty cycle is reduced, the overall power
      consumption approaches the standby power. The protocol is implemented in hardware
      as part of the Sensiumtrade system-on-chip WBASN ASIC, in a 0.13- mum CMOS
      process. 

PMID- 23853129
TI  - Micro-Magnetocardiography System With a Single-Chip SQUID Magnetometer Array for
      QT Analysis and Diagnosis of Myocardial Injury in Small Animals.
AB  - Development of drugs requires electrophysiological studies of small animals like
      mice, rats or guinea pigs. Electrocardiography (ECG) of hirsute animals is time
      consuming. We have developed a micro magnetometer array with a 9-channel
      superconducting quantum interference device (SQUID) with a 2.5-mm diameter pickup
      coil for noncontacting measurement of magnetocardiograms (MCGs) in small animals.
      The micro-MCG successfully recorded the PQRST complex in mice, rats and guinea
      pigs. A regional myocardial injury was made in rat hearts with a cryoinjury
      probe, and the characteristic pattern of the injury was recorded in the MCG. An
      anterior myocardial injury created a QS pattern in the MCG, and a posterior
      myocardial injury created a QR pattern in the MCG. Quinidine-induced QT
      prolongation was successfully detected by micro-MCG in mice and rats.
      Simultaneous recording of ECG and MCG was conducted after intraperitoneal
      administration of quinidine (60 mg/kg) in guinea pigs. QT interval corrected for
      heart rate (QTc) in both ECG and MCG correlated well. The newly developed micro
      MCG may facilitate electrophysiological studies of small animals, and may enable
      high-throughput screening of drug-induced QT abnormality. 

PMID- 23853130
TI  - Effects of inertia and wrist oscillations on contralateral neurological postural
      tremor using the wristalyzer, a new myohaptic device.
AB  - Upper limb postural tremor consists of mechanical-reflex and central-neurogenic
      oscillations, superimposed upon a background of irregular fluctuations in muscle
      force. Muscle spindles play key-roles in the information flow to supra-spinal and
      spinal generators. Oscillations were delivered using a new generation portable
      myohaptic device, called ldquowristalyzer,rdquo taking into account the ergonomy
      of upper limbs and allowing a fine adjustment to each configuration of upper limb
      segments. The nominal torque of the first generation device is 4 Nm, with a
      maximal rotation velocity of 300 degrees/s and a range of motion of plusmn45
      degrees. Reliability was assessed in basal condition and during loading
      conditions. We assessed the effects of the addition of inertia on postural tremor
      of the finger in a group of 26 neurological patients and the effects of wrist
      oscillations upon contralateral postural tremor in 6 control subjects and in 7
      neurological patients exhibiting a postural tremor. Patients showed two different
      behaviors in response to inertia and exhibited an increased variability of
      postural tremor during fast oscillations (13.3 Hz). One patient with overactivity
      of the olivocerebellar pathways exhibited a drop in the peak frequency of more
      than 20%. The relative power of the 8-12 Hz subband was significantly higher in
      controls both in basal condition and during oscillations (p = 0.028 and p =
      0.015, respectively). The second generation wristalyzer allows to investigate the
      effects of mechanical oscillations up to frequency of 50 Hz. This mechatronic
      device can assess the responsiveness of tremor generators to stimulation of
      muscle spindles and biomechanical loading. Potential applications are the
      monitoring of dysmetria under various inertial or damping conditions, the
      assessment of rigidity in Parkinson's disease and the characterization of
      voluntary muscle force. 

PMID- 23853131
TI  - A Low-Power CMOS Front-End for Photoplethysmographic Signal Acquisition With
      Robust DC Photocurrent Rejection.
AB  - A micro-power CMOS front-end, consisting of a transimpedance amplifier (TIA) and
      an ultralow cutoff frequency lowpass filter for the acquisition of
      photoplethysmographic signal (PPG) is presented. Robust DC photocurrent rejection
      for the pulsed signal source is achieved through a sample-and-hold stage in the
      feed-forward signal path and an error amplifier in the feedback path. Ultra-low
      cutoff frequency of the filter is achieved with a proposed technique that
      incorporates a pair of current-steering transistors that increases the effective
      filter capacitance. The design was realized in a 0.35-mum CMOS technology. It
      consumes 600 muW at 2.5 V, rejects DC photocurrent ranged from 100 nA to 53.6
      muA, and achieves lower-band and upper-band - 3-dB cutoff frequencies of 0.46 and
      2.8 Hz, respectively. 

PMID- 23853132
TI  - On the thermal elevation of a 60-electrode epiretinal prosthesis for the blind.
AB  - In this paper, the thermal elevation in the human body due to the operation of a
      dual-unit epiretinal prosthesis to restore partial vision to the blind affected
      by irreversible retinal degeneration is presented. An accurate computational
      model of a 60-electrode device dissipating 97 mW power, currently under clinical
      trials is developed and positioned in a 0.25 mm resolution, heterogeneous model
      of the human head to resemble actual conditions of operation of the prosthesis. A
      novel simple finite difference scheme combining the explicit and the alternating
      direction implicit (ADI) method has been developed and validated with existing
      methods. Simulation speed improvement up to 11 times was obtained for the the
      head model considered in this work with very good accuracy. Using this method,
      solutions of the bioheat equation were obtained for different placements of the
      implant. Comparison with in-vivo experimental measurements showed good agreement.

PMID- 23853134
TI  - An analog integrated-circuit vocal tract.
AB  - We present the first experimental integrated-circuit vocal tract by mapping fluid
      volume velocity to current, fluid pressure to voltage, and linear and nonlinear
      mechanical impedances to linear and nonlinear electrical impedances. The 275 muW
      analog vocal tract chip includes a 16-stage cascade of two-port pi-elements that
      forms a tunable transmission line, electronically variable impedances, and a
      current source as the glottal source. A nonlinear resistor models laminar and
      turbulent flow in the vocal tract. The measured SNR at the output of the analog
      vocal tract is 64, 66, and 63 dB for the first three formant resonances of a
      vocal tract with uniform cross-sectional area. The analog vocal tract can be used
      with auditory processors in a feedback speech locked loop-analogous to a phase
      locked loop-to implement speech recognition that is potentially robust in noise.
      Our use of a physiological model of the human vocal tract enables the analog
      vocal tract chip to synthesize speech signals of interest, using articulatory
      parameters that are intrinsically compact and linearly interpolatable. 

PMID- 23853133
TI  - Power-efficient impedance-modulation wireless data links for biomedical implants.
AB  - We analyze the performance of wireless data telemetry links for implanted
      biomedical systems. An experimental realization of a bidirectional half-duplex
      link that uses near-field inductive coupling between the implanted system and an
      external transceiver is described. Our system minimizes power consumption in the
      implanted system by using impedance modulation to transmit high-bandwidth
      information in the uplink direction, i.e., from the implanted to the external
      system. We measured a data rate of 2.8 Mbps at a bit error rate (BER) of <10(-6)
      (we could not measure error rates below 10(-6) ) and a data rate of 4.0 Mbps at a
      BER of 10(-3). Experimental results also demonstrate data transfer rates up to
      300 kbps in the opposite, i.e., downlink direction. We also perform a theoretical
      analysis of the bit error rate performance. An important effect regarding the
      asymmetry of rising and falling edges that is inherent to impedance modulation is
      predicted by theory and confirmed by experiment. The link dissipates 2.5 mW in
      the external system and only 100 muW in the implanted system, making it among the
      most power-efficient inductive data links reported. Our link is compatible with
      FCC regulations on radiated emissions. 

PMID- 23853135
TI  - A new antispoofing approach for biometric devices.
AB  - The deployment of fingerprint sensors is increasingly becoming common and has now
      gained high user acceptance. However, fingerprint sensors are susceptible to
      spoofing using artificial materials or in worst case to the dismembered fingers.
      Fake/gummy fingerprints have shown to fool most commercial fingerprint systems.
      This paper proposes a new method of anti-spoofing using reliable liveness
      detection. The proposed method of liveness detection is based on the principle of
      pulse oximetry and involves the source of light originating from a probe at two
      wavelengths. The light is partly absorbed by haemoglobin, by amounts which differ
      depending on whether it is saturated with oxygen or deoxygenated haemoglobin. We
      then perform the computations for the absorption at two wavelengths to estimate
      the proportion of haemoglobin which is oxygenated. The computed percentage of
      oxygen in the blood, along with the heart pulse rate, determines the liveness of
      the enrolled biometric. Our experimental results demonstrate that the developed
      prototype can successfully thwart the spoof attacks (including those based on
      dismembered fingers). 

PMID- 23853136
TI  - Impact of temperature on Na2 Sr(PO4)F:Eu3+ phosphor.
AB  - In this article, we report the synthesis of Na2 Sr1-x (PO4)F:Eux phosphor via a
      combustion method. The influence of different annealing temperatures on the
      photoluminescence properties was investigated. The phosphor was excited at both
      254 and 393 nm. Na2 Sr1-x (PO4)F:Eux (3+) phosphors emit strong orange and red
      color at 593 and 612 nm, respectively, under both excitation wavelengths. Na2 Sr1
      x (PO4)F:Eux (3+) phosphors annealed at 1050 degrees C showed stronger emission
      intensity compared with 600, 900 and 1200 degrees C. Moreover, Na2 Sr1-x
      (PO4)F:Eux (3+) phosphor was found to be more intense when compared with
      commercial Y2 O3:Eu(3+) phosphor.

PMID- 23853137
TI  - Neurological picture. Conjugate upward gaze paralysis with unilateral ptosis
      caused by a unilateral midbrain infarction.

PMID- 23853138
TI  - Brain arteriovenous malformations and seizures: an Italian study.
AB  - OBJECTIVE: To evaluate seizures as first clinical manifestation of brain
      arteriovenous malformations (AVMs), in relation to angioarchitectural features of
      these vascular anomalies. METHODS: We performed a prospective observational
      study, collecting records of patients with AVMs consecutively admitted to the
      Neurological and Neurosurgery Units of Perugia University and to the Neurosurgery
      Unit of Terni Hospital, during a 10-year period (1 January 2002 to 1 June 2012).
      Two groups of patients, with or without seizures as AVM first presentation, were
      analysed to identify differences in demographic and angiographic features. A
      multivariate logistic regression model was also developed. RESULTS: We examined
      101 patients with AVMs, 55 male and 46 female. Seizures were the initial clinical
      manifestation in 31 (30.7%) patients. We found a significant difference (p<0.05)
      between two groups of patients, with or without seizures as AVM first
      presentation concerning location, side, topography and venous drainage. A
      multivariate logistic regression model showed that clinical presentation with
      seizures was correlated with a location in the temporal and frontal lobes, and
      with a superficial topography. The strongest association (OR 3.48; 95% CI 1.77 to
      6.85) was observed between seizures and AVM location in the temporal lobe.
      CONCLUSIONS: Vascular remodelling and haemodynamic changes of AVMs might create
      conditions for epileptogenesis. However, here we show that malformations with
      specific angiographic characteristics are more likely to be associated with
      seizures as first clinical presentation. Location is the most important feature
      related to epilepsy and in particular the temporal lobe might play a crucial role
      in the occurrence of seizure.

PMID- 23853139
TI  - Stereo-EEG-guided radio-frequency thermocoagulations of epileptogenic grey-matter
      nodular heterotopy.
AB  - OBJECTIVE: To retrospectively evaluate seizure outcome in a case-series of
      patients with nodular heterotopy (NH)-related epilepsy treated by stereo-EEG
      (SEEG)-guided radio-frequency thermocoagulation (RF-THC) of the NH. METHODS: Five
      patients (three male, age 5-33 years) with drug-resistant focal epilepsy
      presented a single NH at brain MRI. Following video-EEG monitoring, patients
      underwent SEEG recording to better identify the epileptogenic zone. All patients
      received RF-THC of the NH, using contiguous contacts of the electrodes employed
      for recording. The contacts for RF-THC lesions were chosen according to
      anatomical (intranodular position) and electrical (intranodular ictal low-voltage
      fast activity) criteria. RESULTS: At SEEG recordings, ictal discharge originated
      from the NH alone in three cases and from the NH and ipsilateral hippocampus in
      one case. In the remaining case, different sites of ictal onset, including the
      NH, were identified within the left frontal lobe. No adverse effects related to
      the RF-THC procedures were observed, apart from a habitual seizure that occurred
      during coagulation in one patient. Postprocedural sustained seizure freedom was
      detected in four cases (mean follow-up 33.5 months). In the case with left
      frontal multifocal ictal activity, RF-THC of the NH provided no benefit on
      seizures, and the patient is seizure-free after left frontal lobe resection.
      CONCLUSIONS: SEEG-guided RF-THC proved to be a safe and effective option in our
      small case-series of NH-related focal epilepsy. The indications to this treatment
      were strictly dependent on findings of intracerebral recording by SEEG, which can
      define the role of the NH in the generation of the ictal discharge.

PMID- 23853140
TI  - Identifying novel phenotypes of vulnerability and resistance to activity-based
      anorexia in adolescent female rats.
AB  - OBJECTIVE: Activity-based anorexia is a translational rodent model that results
      in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of
      our investigation was to identify vulnerable and resistant phenotypes of activity
      based anorexia in adolescent female rats. METHOD: Sprague-Dawley rats were
      maintained under conditions of restricted access to food (N = 64; or unlimited
      access, N = 16) until experimental exit, predefined as a target weight loss of 30
      35% or meeting predefined criteria for animal health. Nonlinear mixed effects
      statistical modeling was used to describe wheel running behavior, time to event
      analysis was used to assess experimental exit, and a regressive partitioning
      algorithm was used to classify phenotypes. RESULTS: Objective criteria were
      identified for distinguishing novel phenotypes of activity-based anorexia,
      including a vulnerable phenotype that conferred maximal hyperactivity, minimal
      food intake, and the shortest time to experimental exit, and a resistant
      phenotype that conferred minimal activity and the longest time to experimental
      exit. DISCUSSION: The identification of objective criteria for defining
      vulnerable and resistant phenotypes of activity-based anorexia in adolescent
      female rats provides an important framework for studying the neural mechanisms
      that promote vulnerability to or protection against the development of self
      starvation and hyperactivity during adolescence. Ultimately, future studies using
      these novel phenotypes may provide important translational insights into the
      mechanisms that promote these maladaptive behaviors characteristic of anorexia
      nervosa.

PMID- 23853141
TI  - Label-free CMOS bio sensor with on-chip noise reduction scheme for real-time
      quantitative monitoring of biomolecules.
AB  - We present a label-free CMOS field-effect transistor sensing array to detect the
      surface potential change affected by the negative charge in DNA molecules for
      real-time monitoring and quantification. The proposed CMOS bio sensor includes a
      new sensing pixel architecture implemented with correlated double sampling for
      reducing offset fixed pattern noise and 1/f noise of the sensing devices. We
      incorporated non-surface binding detection which allows real-time continuous
      monitoring of DNA concentrations without immobilizing them on the sensing
      surface. Various concentrations of 19-bp oligonucleotides solution can be
      discriminated using the prototype device fabricated in 1- MUm double-poly double
      metal standard CMOS process. The detection limit was measured as 1.1 ng/MUl with
      a dynamic range of 40 dB and the transient response time was measured less than
      20 seconds. 

PMID- 23853142
TI  - A tripolar current-steering stimulator ASIC for field shaping in deep brain
      stimulation.
AB  - A significant problem with clinical deep brain stimulation (DBS) is the high
      variability of its efficacy and the frequency of side effects, related to the
      spreading of current beyond the anatomical target area. This is the result of the
      lack of control that current DBS systems offer on the shaping of the electric
      potential distribution around the electrode. This paper presents a stimulator
      ASIC with a tripolar current-steering output stage, aiming at achieving more
      selectivity and field shaping than current DBS systems. The ASIC was fabricated
      in a 0.35-MU m CMOS technology occupying a core area of 0.71 mm(2). It consists
      of three current sourcing/sinking channels. It is capable of generating square
      and exponential-decay biphasic current pulses with five different time constants
      up to 28 ms and delivering up to 1.85 mA of cathodic current, in steps of 4 MUA,
      from a 12 V power supply. Field shaping was validated by mapping the potential
      distribution when injecting current pulses through a multicontact DBS electrode
      in saline. 

PMID- 23853143
TI  - Analysis of dual band power and data telemetry for biomedical implants.
AB  - Inductive coupling is commonly used for wireless power and data transfer in
      biomedical telemetry systems. To increase data bandwidth while maintaining power
      transfer efficiency, a multiband telemetry system transmitting power and data
      using different frequencies has been adopted. However, the power link and data
      link interact with each other, complicating the operation of both power and data
      transmission. In this paper, we demonstrate that to achieve high performance data
      transmission, the cross-coupling between the power coils and data coils have to
      be taken into consideration. Design equations have been derived and shown that
      the signal to noise (interference) ratio could be significantly reduced and the
      resulting data transmission could fail if only the data link coupling is
      optimized without considering the cross-coupling between the power link and the
      data link. Design examples have been constructed to demonstrate that there could
      be more than 30 dB difference in the signal to noise ratio. The analysis has been
      verified with simulation and measurement results. 

PMID- 23853144
TI  - Active books: the design of an implantable stimulator that minimizes cable count
      using integrated circuits very close to electrodes.
AB  - This paper presents an integrated stimulator that can be embedded in implantable
      electrode books for interfacing with nerve roots at the cauda equina. The Active
      Book overcomes the limitation of conventional nerve root stimulators which can
      only support a small number of stimulating electrodes due to cable count
      restriction through the dura. Instead, a distributed stimulation system with many
      tripole electrodes can be configured using several Active Books which are
      addressed sequentially. The stimulator was fabricated in a 0.6-MUm high-voltage
      CMOS process and occupies a silicon area of 4.2 * 6.5 mm(2). The circuit was
      designed to deliver up to 8 mA stimulus current to tripole electrodes from an 18
      V power supply. Input pad count is limited to five (two power and three control
      lines) hence requiring a specific procedure for downloading stimulation commands
      to the chip and extracting information from it. Supported commands include
      adjusting the amplitude of stimulus current, varying the current ratio at the two
      anodes in each channel, and measuring relative humidity inside the chip package.
      In addition to stimulation mode, the chip supports quiescent mode, dissipating
      less than 100 nA current from the power supply. The performance of the stimulator
      chip was verified with bench tests including measurements using tripoles in
      saline. 

PMID- 23853145
TI  - Maximum achievable efficiency in near-field coupled power-transfer systems.
AB  - Wireless power transfer is commonly realized by means of near-field inductive
      coupling and is critical to many existing and emerging applications in biomedical
      engineering. This paper presents a closed form analytical solution for the
      optimum load that achieves the maximum possible power efficiency under arbitrary
      input impedance conditions based on the general two-port parameters of the
      network. The two-port approach allows one to predict the power transfer
      efficiency at any frequency, any type of coil geometry and through any type of
      media surrounding the coils. Moreover, the results are applicable to any form of
      passive power transfer such as provided by inductive or capacitive coupling. Our
      results generalize several well-known special cases. The formulation allows the
      design of an optimized wireless power transfer link through biological media
      using readily available EM simulation software. The proposed method effectively
      decouples the design of the inductive coupling two-port from the problem of
      loading and power amplifier design. Several case studies are provided for typical
      applications. 

PMID- 23853146
TI  - Energy-efficient neuron, synapse and STDP integrated circuits.
AB  - Ultra-low energy biologically-inspired neuron and synapse integrated circuits are
      presented. The synapse includes a spike timing dependent plasticity (STDP)
      learning rule circuit. These circuits have been designed, fabricated and tested
      using a 90 nm CMOS process. Experimental measurements demonstrate proper
      operation. The neuron and the synapse with STDP circuits have an energy
      consumption of around 0.4 pJ per spike and synaptic operation respectively. 

PMID- 23853147
TI  - BioThreads: a novel VLIW-based chip multiprocessor for accelerating biomedical
      image processing applications.
AB  - We discuss BioThreads, a novel, configurable, extensible system-on-chip
      multiprocessor and its use in accelerating biomedical signal processing
      applications such as imaging photoplethysmography (IPPG). BioThreads is derived
      from the LE1 open-source VLIW chip multiprocessor and efficiently handles
      instruction, data and thread-level parallelism. In addition, it supports a novel
      mechanism for the dynamic creation, and allocation of software threads to
      uncommitted processor cores by implementing key POSIX Threads primitives directly
      in hardware, as custom instructions. In this study, the BioThreads core is used
      to accelerate the calculation of the oxygen saturation map of living tissue in an
      experimental setup consisting of a high speed image acquisition system, connected
      to an FPGA board and to a host system. Results demonstrate near-linear
      acceleration of the core kernels of the target blood perfusion assessment with
      increasing number of hardware threads. The BioThreads processor was implemented
      on both standard-cell and FPGA technologies; in the first case and for an issue
      width of two, full real-time performance is achieved with 4 cores whereas on a
      mid-range Xilinx Virtex6 device this is achieved with 10 dual-issue cores. An 8
      core LE1 VLIW FPGA prototype of the system achieved 240 times faster execution
      time than the scalar Microblaze processor demonstrating the scalability of the
      proposed solution to a state-of-the-art FPGA vendor provided soft CPU core. 

PMID- 23853148
TI  - A wireless reflectance pulse oximeter with digital baseline control for
      unfiltered photoplethysmograms.
AB  - Pulse oximeters are central to the move toward wearable health monitoring devices
      and medical electronics either hosted by, e.g., smart phones or physically
      embedded in their design. This paper presents a small, low-cost pulse oximeter
      design appropriate for wearable and surface-based applications that also produces
      quality, unfiltered photo-plethysmograms (PPGs) ideal for emerging diagnostic
      algorithms. The design's "filter-free" embodiment, which employs only digital
      baseline subtraction as a signal compensation mechanism, distinguishes it from
      conventional pulse oximeters that incorporate filters for signal extraction and
      noise reduction. This results in high-fidelity PPGs with thousands of peak-to
      peak digitization levels that are sampled at 240 Hz to avoid noise aliasing.
      Electronic feedback controls make these PPGs more resilient in the face of
      environmental changes (e.g., the device can operate in full room light), and data
      stream in real time across either a ZigBee wireless link or a wired USB
      connection to a host. On-board flash memory is available for store-and-forward
      applications. This sensor has demonstrated an ability to gather high-integrity
      data at fingertip, wrist, earlobe, palm, and temple locations from a group of 48
      subjects (20 to 64 years old). 

PMID- 23853149
TI  - Power flow control based solely on slow feedback loop for heart pump
      applications.
AB  - This paper proposes a new control method for regulating power flow via
      transcutaneous energy transfer (TET) for implantable heart pumps. Previous work
      on power flow controller requires a fast feedback loop that needs additional
      switching devices and resonant capacitors to be added to the primary converter.
      The proposed power flow controller eliminates these additional components, and it
      relies solely on a slow feedback loop to directly drive the primary converter to
      meet the heart pump power demand and ensure zero voltage switching. A controlled
      change in switching frequency varies the resonant tank shorting period of a
      current-fed push-pull resonant converter, thus changing the magnitude of the
      primary resonant voltage, as well as the tuning between primary and secondary
      resonant tanks. The proposed controller has been implemented successfully using
      an analogue circuit and has reached an end-to-end power efficiency of 79.6% at 10
      W with a switching frequency regulation range of 149.3 kHz to 182.2 kHz. 

PMID- 23853150
TI  - A linear parametric approach for analysis of mouse respiratory impedance.
AB  - Assessment of the lung mechanics is crucial in lung function studies. Commonly
      lung mechanics is achieved through measurement of the input impedance of the lung
      where the experimental data is ideal for the application of system identification
      techniques. This study proposes a new approach for investigating the severity of
      lung conditions and also evaluating the treatment progression. The proposed
      method is established based on linear parametric identification of lung input
      impedance in mice and is applied to normal and asthmatic models (including acute,
      tolerant and chronic asthma) as well as a pharmacological intervention model.
      Experimental findings confirm the effectiveness of the analysis technique applied
      here. We discuss the potential application of this method to analyses of human
      lung mechanics. 

PMID- 23853151
TI  - Fullerene-bisadduct acceptors for polymer solar cells.
AB  - Polymer solar cells (PSCs) have drawn great attention in recent years for their
      simple device structure, light weight, and low-cost fabrication in comparison
      with inorganic semiconductor solar cells. However, the power-conversion
      efficiency (PCE) of PSCs needs to be increased for their future application. The
      key issue for improving the PCE of PSCs is the design and synthesis of high
      efficiency conjugated polymer donors and fullerene acceptors for the photovoltaic
      materials. For the acceptor materials, several fullerene-bisadduct acceptors with
      high LUMO energy levels have demonstrated excellent photovoltaic performance in
      PSCs with P3HT as a donor. In this Focus Review, recent progress in high
      efficiency fullerene-bisadduct acceptors is discussed, including the bisadduct of
      PCBM, indene-C60 bisadduct (ICBA), indene-C70 bisadduct (IC70BA), DMPCBA, NCBA,
      and bisTOQC. The LUMO levels and photovoltaic performance of these bisadduct
      acceptors with P3HT as a donor are summarized and compared. In addition, the
      applications of an ICBA acceptor in new device structures and with other
      conjugated polymer donors than P3HT are also introduced and discussed.

PMID- 23853153
TI  - A joint photoelectron spectroscopy and theoretical study on the electronic
      structure of UCl5- and UCl5.
AB  - We report a combined photoelectron spectroscopic and relativistic quantum
      chemistry study on gaseous UCl5(-) and UCl5. The UCl5(-) anion is produced using
      electrospray ionization and found to be highly electronically stable with an
      adiabatic electron binding energy of 4.76+/-0.03 eV, which also represents the
      electron affinity of the neutral UCl5 molecule. Theoretical investigations reveal
      that the ground state of UCl5(-) has an open shell with two unpaired electrons
      occupying two primarily U 5f(z3) and 5f(xyz) based molecular orbitals. The
      structures of both UCl5(-) and UCl5 are theoretically optimized and confirmed to
      have C(4v) symmetry. The computational results are in good agreement with the
      photoelectron spectra, providing insights into the electronic structures and
      valence molecular orbitals of UCl5(-) and UCl5. We also performed systematic
      theoretical studies on all the uranium pentahalide complexes UX5(-) (X=F, Cl, Br,
      I). Chemical bonding analyses indicate that the U-X interactions in UX5(-) are
      dominated by ionic bonding, with increasing covalent contributions for the
      heavier halogen complexes.

PMID- 23853154
TI  - Monitoring of tumor response to cisplatin with simultaneous fluorescence and
      positron emission tomography: a feasibility study.
AB  - Dual modality molecular imaging can capture concurrent molecular events and
      evaluate therapeutic efficacy from uniquely different perspectives based on
      different molecular targets. In this work, dual modality tomographic imaging,
      (18) F-fluorodeoxyglucose based positron emission tomography and subsurface
      fluorescence molecular tomography ([(18) F]FDG-PET/subsurface FMT), is proposed
      to monitor tumor response to cisplatin on a mouse xenograft model in vivo. One
      mouse was administered with cisplatin (1.0 mg/kg) by intraperitoneal injection
      once every day for 14 days, and another mouse was administered with saline to
      serve as the control. Dual modality [(18) F]FDG-PET/subsurface FMT imaging was
      conducted on days 0, 2, 5, 9, 15, and 22. In vivo imaging and quantitative
      analysis demonstrated the feasibility of [(18) F]FDG-PET/subsurface FMT imaging
      in tracking the changes of [(18) F]FDG tumor uptake and amount of red fluorescent
      protein (RFP) synthesized by tumor cells in the same mouse simultaneously. Dual
      modality [(18) F]FDG-PET/subsurface FMT imaging may thus provide a powerful tool
      for better understanding disease progress and treatment evaluation from different
      perspectives.

PMID- 23853155
TI  - The impact of maternal obesity and gestational weight gain on early and mid
      pregnancy lipid profiles.
AB  - OBJECTIVE: The impact of maternal overweight/obesity and excessive weight gain on
      maternal serum lipids in the first and second trimester of pregnancy was
      evaluated. METHODS: Prospective data were collected for 225 women. Maternal serum
      lipids and fatty acids were measured at <13 weeks and between 24 and 28 weeks.
      Analyses were stratified by normal weight versus overweight/obese status and
      excessive versus nonexcessive weight gain. RESULTS: Overweight/obese women had
      higher baseline cholesterol (161.3 +/- 29.6 vs. 149.4 +/- 26.8 mg/dl, P < 0.01),
      low-density lipoprotein LDL (80.0 +/- 19.9 vs. 72.9 +/- 18.8 mg/dl, P < 0.01),
      and triglycerides (81.7 +/- 47.2 vs. 69.7 +/- 40.3 mg/dl, P = 0.05) when compared
      to normal weight women, whereas high-density lipoprotein (43.6 +/- 10.4 vs. 47.6
      +/- 11.5 mg/dl, P < 0.01) was lower. However, cholesterol and LDL increased at a
      higher weekly rate in normal weight women, resulting in higher total cholesterol
      in normal weight women (184.1 +/- 28.1 vs. 176.0 +/- 32.1 mg/dl, P = 0.05) at 24
      28 weeks. The rate of change in lipid profiles in either group was not affected
      by excessive weight gain. Overweight/obese women had higher levels of arachidonic
      acid at both time points. CONCLUSIONS: Overweight/obese women have significantly
      more atherogenic lipid profiles than normal weight women during the period of
      early pregnancy, delineating one physiologic pathway between that could explain
      differences in pregnancy outcomes normal weight and overweight/obese women.

PMID- 23853156
TI  - The stress process and eating pathology among racially diverse adolescents
      seeking treatment for obesity.
AB  - OBJECTIVE: This study examined the associations of weight-related teasing and
      daily hassles with eating pathology, as well as potential mediators of these
      relations, among a racially diverse sample of adolescents. METHODS: Participants
      were 92 primarily African American 11-17-year-olds seeking treatment for obesity.
      Data were collected at baseline. RESULTS: Both daily hassles and weight-related
      teasing were significantly correlated with eating pathology at r = .22 and r =
      .25, respectively. Feeling upset about teasing mediated the associations of daily
      hassles (PE = .0093, SE = .0054, 95% BCa bootstrap CI of .0001-.0217) and teasing
      (PE = .0476, SE = .0198, 95% BCa bootstrap CI of .0093-.0873) with eating
      pathology. CONCLUSIONS: These results highlight the importance of psychological
      interventions in the treatment of weight-loss among adolescents, as stressors may
      impact eating behaviors.

PMID- 23853157
TI  - Local gene expression in nerve endings.
AB  - At the Nobel lecture for physiology in 1906, Ramon y Cajal famously stated that
      "the nerve elements possess reciprocal relationships in contiguity but not in
      continuity," summing up the neuron doctrine. Sixty years later, by the time the
      central dogma of molecular biology formulated the axis of genetic information
      flow from DNA to mRNA, and then to protein, it became obvious that neurons with
      extensive ramifications and long axons inevitably incur an innate problem: how
      can the effect of gene expression be extended from the nucleus to the remote and
      specific sites of the cell periphery? The most straightforward solution would be
      to deliver soma-produced proteins to the target sites. The influential discovery
      of axoplasmic flow has supported this scheme of protein supply. Alternatively,
      mRNAs can be dispatched instead of protein, and translated locally at the
      strategic target sites. Over the past decades, such a local system of protein
      synthesis has been demonstrated in dendrites, axons, and presynaptic terminals.
      Moreover, the local protein synthesis in neurons might even involve intercellular
      trafficking of molecules. The innovative concept of glia-neuron unit suggests
      that the local protein synthesis in the axonal and presynaptic domain of mature
      neurons is sustained by a local supply of RNAs synthesized in the surrounding
      glial cells and transferred to these domains. Here, we have reviewed some of the
      evidence indicating the presence of a local system of protein synthesis in axon
      terminals, and have examined its regulation in various model systems.

PMID- 23853159
TI  - A Wireless Capsule Endoscope System With Low-Power Controlling and Processing
      ASIC.
AB  - This paper presents the design of a wireless capsule endoscope system. The
      proposed system is mainly composed of a CMOS image sensor, a RF transceiver and a
      low-power controlling and processing application specific integrated circuit
      (ASIC). Several design challenges involving system power reduction, system
      miniaturization and wireless wake-up method are resolved by employing optimized
      system architecture, integration of an area and power efficient image compression
      module, a power management unit (PMU) and a novel wireless wake-up subsystem with
      zero standby current in the ASIC design. The ASIC has been fabricated in 0.18-mum
      CMOS technology with a die area of 3.4 mm * 3.3 mm. The digital baseband can work
      under a power supply down to 0.95 V with a power dissipation of 1.3 mW. The
      prototype capsule based on the ASIC and a data recorder has been developed. Test
      result shows that proposed system architecture with local image compression lead
      to an average of 45% energy reduction for transmitting an image frame. 

PMID- 23853158
TI  - RNA-binding protein Vg1RBP regulates terminal arbor formation but not long-range
      axon navigation in the developing visual system.
AB  - Local synthesis of beta-actin is required for attractive turning responses to
      guidance cues of growth cones in vitro but its functional role in axon guidance
      in vivo is poorly understood. The transport and translation of beta-actin mRNA is
      regulated by the RNA-binding protein, Vg1RBP (zipcode-binding protein-1). To
      examine whether Vg1RBP plays a role in axon navigation in vivo, we disrupted
      Vg1RBP function in embryonic Xenopus laevis retinal ganglion cells by expressing
      a dominant-negative Vg1RBP and by antisense morpholino knockdown. We found that
      attractive turning to a netrin-1 gradient in vitro was abolished in Vg1RBP
      deficient axons but, surprisingly, the long-range navigation from the retina to
      the optic tectum was unaffected. Within the tectum, however, the branching and
      complexity of axon terminals were significantly reduced. High-resolution time
      lapse imaging of axon terminals in vivo revealed that Vg1RBP-GFP-positive
      granules accumulate locally in the axon shaft immediately preceding the emergence
      a filopodial-like protrusion. Comparative analysis of branch dynamics showed that
      Vg1RBP-deficient axons extend far fewer filopodial-like protrusions than control
      axons and indicate that Vg1RBP promotes filopodial formation, an essential step
      in branch initiation. Our findings show that Vg1RBP is required for terminal
      arborization but not long-range axon navigation and suggest that Vg1RBP-regulated
      mRNA translation promotes synaptic complexity.

PMID- 23853160
TI  - Analysis, design, and control of a transcutaneous power regulator for artificial
      hearts.
AB  - Based on a generic transcutaneous transformer model, a remote power supply using
      a resonant topology for use in artificial hearts is analyzed and designed for
      easy controllability and high efficiency. The primary and secondary windings of
      the transcutaneous transformer are positioned outside and inside the human body,
      respectively. In such a transformer, the alignment and gap may change with
      external positioning. As a result, the coupling coefficient of the transcutaneous
      transformer is also varying, and so are the two large leakage inductances and the
      mutual inductance. Resonant-tank circuits with varying resonant-frequency are
      formed from the transformer inductors and external capacitors. For a given range
      of coupling coefficients, an operating frequency corresponding to a particular
      coupling coefficient can be found, for which the voltage transfer function is
      insensitive to load. Prior works have used frequency modulation to regulate the
      output voltage under varying load and transformer coupling. The use of frequency
      modulation may require a wide control frequency range which may extend well above
      the load insensitive frequency. In this paper, study of the input-to-output
      voltage transfer function is carried out, and a control method is proposed to
      lock the switching frequency at just above the load insensitive frequency for
      optimized efficiency at heavy loads. Specifically, operation at above resonant of
      the resonant circuits is maintained under varying coupling-coefficient. Using a
      digital-phase-lock-loop (PLL), zero-voltage switching is achieved in a full
      bridge converter which is also programmed to provide output voltage regulation
      via pulsewidth modulation (PWM). A prototype transcutaneous power regulator is
      built and found to to perform excellently with high efficiency and tight
      regulation under variations of the alignment or gap of the transcutaneous
      transformer, load and input voltage. 

PMID- 23853161
TI  - Real-Time Classification of Complex Patterns Using Spike-Based Learning in
      Neuromorphic VLSI.
AB  - Real-time classification of patterns of spike trains is a difficult computational
      problem that both natural and artificial networks of spiking neurons are
      confronted with. The solution to this problem not only could contribute to
      understanding the fundamental mechanisms of computation used in the biological
      brain, but could also lead to efficient hardware implementations of a wide range
      of applications ranging from autonomous sensory-motor systems to brain-machine
      interfaces. Here we demonstrate real-time classification of complex patterns of
      mean firing rates, using a VLSI network of spiking neurons and dynamic synapses
      which implement a robust spike-driven plasticity mechanism. The learning rule
      implemented is a supervised one: a teacher signal provides the output neuron with
      an extra input spike-train during training, in parallel to the spike-trains that
      represent the input pattern. The teacher signal simply indicates if the neuron
      should respond to the input pattern with a high rate or with a low one. The
      learning mechanism modifies the synaptic weights only as long as the current
      generated by all the stimulated plastic synapses does not match the output
      desired by the teacher, as in the perceptron learning rule. We describe the
      implementation of this learning mechanism and present experimental data that
      demonstrate how the VLSI neural network can learn to classify patterns of neural
      activities, also in the case in which they are highly correlated. 

PMID- 23853162
TI  - An analytical model for inductively coupled implantable biomedical devices with
      ferrite rods.
AB  - Using approximations applicable to near field coupled implants simplified
      expressions for the complex mutual inductance of coaxial aligned coils with and
      without a cylindrical ferrite rod are derived. Experimental results for ferrite
      rods of various sizes and permeabilities are presented to verify the accuracy of
      this expression. An equivalent circuit model for the inductive link between an
      implant and power coil is then presented and used to investigate how ferrite
      size, permeability and loss affect the power available to the implant device.
      Enhancements in coupling provided by high frequency, low permeability nickel zinc
      rods are compared with low frequency high permeability manganese zinc rods. 

PMID- 23853163
TI  - Systematic Design and Modeling of a OTA-C Filter for Portable ECG Detection.
AB  - This study presents a systematic design of the fully differential operational
      transconductance amplifier-C (OTA-C) filter for a heart activities detection
      apparatus. Since the linearity and noise of the filter is dependent on the
      building cell, a precise behavioral model for the real OTA circuit is created. To
      reduce the influence of coefficient sensitivity and maintain an undistorted
      biosignal, a fifth-order ladder-type lowpass Butterworth is employed. Based on
      this topology, a chip fabricated in a 0.18- mum CMOS process is simulated and
      measured to validate the system estimation. Since the battery life and the
      integration with the low-voltage digital processor are the most critical
      requirement for the portable diagnosis device, the OTA-based circuit is operated
      in the subthreshold region to save power under the supply voltage of 1V.
      Measurement results show that this low-voltage and low-power filter possesses the
      HD3 of -48.9 dB, dynamic range (DR) of 50 dB, and power consumption of 453 nW.
      Therefore, the OTA-C filter can be adopted to eliminate the out-of-band
      interference of the electrocardiogram (ECG) whose signal bandwidth is located
      within 250 Hz. 

PMID- 23853165
TI  - Retinal haemorrhage, subretinal pigment epithelial deposits and serous macular
      detachment in light chain deposition disease.

PMID- 23853166
TI  - Intra-arterial chemotherapy with melphalan for intraocular retinoblastoma.

PMID- 23853167
TI  - Traumatic retinopathy presenting as acute macular neuroretinopathy.
AB  - AIM: Traumatic retinopathy presenting as acute macular neuroretinopathy (AMNR) is
      an uncommon disease causing paracentral scotomas after indirect trauma. METHODS:
      We report on five patients (six eyes) with AMNR with a temporary reduction of
      visual acuity and persistent paracentral scotomas after indirect trauma. The
      findings were documented using multimodal imaging and the follow-up was up to 32
      months. RESULTS: Initially, fundoscopy was unremarkable in all patients while
      visual acuity (Snellen equivalents) varied between 0.03 and 1.0, and a
      paracentral scotoma was present in all patients. During follow-up, visual acuity
      recovered to 1.0 in all patients while the paracentral scotomas persisted.
      Spectral-domain optical coherence tomography revealed a disruption of the
      inner/outer segment junction within the macular lesion and changes in the outer
      nuclear layer, which slowly recovered partly during the follow-up. CONCLUSIONS:
      These findings suggest that indirect trauma can cause changes in the outer retina
      resembling those seen in AMNR, resulting in persisting paracentral scotomas.

PMID- 23853168
TI  - The long-term psychosocial impact of corrective surgery for adults with
      strabismus.

PMID- 23853169
TI  - Talking to patients about a diagnosis of malignancy in a fine-needle aspiration
      clinic setting.

PMID- 23853170
TI  - Chronic treatment with novel GPR40 agonists improve whole-body glucose metabolism
      based on the glucose-dependent insulin secretion.
AB  - GPR40 is a free fatty acid receptor that has been shown to regulate glucose
      dependent insulin secretion. This study aimed to discover novel GPR40 agonists
      and investigate the whole-body effect on glucose metabolism of GPR40 activation
      using these novel GPR40 agonists. To identify novel GPR40-specific agonists, we
      conducted high-throughput chemical compound screening and evaluated glucose
      dependent insulin secretion. To investigate the whole-body effect on glucose
      metabolism of GPR40 activation, we conducted repeat administration of the novel
      GPR40 agonists to diabetic model ob/ob mice and evaluated metabolic parameters.
      To characterize the effect of the novel GPR40 agonists more deeply, we conducted
      an insulin tolerance test and a euglycemic-hyperinsulinemic clamp test. As a
      result, we discovered the novel GPR40-specific agonists, including AS2034178
      [bis{2-[(4-{[4'-(2-hydroxyethoxy)-2'-methyl[1,1'-biphenyl]-3
      yl]methoxy}phenyl)methyl]-3,5-dioxo-1,2,4-oxadiazolidin-4-ide} tetrahydrate], and
      found that its exhibited glucose-dependent insulin secretion enhancement both in
      vitro and in vivo. In addition, the compounds also decreased plasma glucose and
      HbA1c levels after repeat administration to ob/ob mice, with favorable oral
      absorption and pharmacokinetics. Repeat administration of AS2034178 enhanced
      insulin sensitivity in an insulin tolerance test and a euglycemic
      hyperinsulinemic clamp test. These results indicate that improvement of glucose
      dependent insulin secretion leads the improvement of whole-body glucose
      metabolism chronically. In conclusion, AS2034178 and other GPR40 agonists may
      become useful therapeutics in the treatment of type 2 diabetes mellitus. 

PMID- 23853172
TI  - Altered structure-function relations of semantic processing in youths with high
      functioning autism: a combined diffusion and functional MRI study.
AB  - Deficits in language and communication are among the core symptoms of autism, a
      common neurodevelopmental disorder with long-term impairment. Despite the
      striking nature of the autistic language impairment, knowledge about its
      corresponding alterations in the brain is still evolving. We hypothesized that
      the dual stream language network is altered in autism, and that this alteration
      could be revealed by changes in the relationships between microstructural
      integrity and functional activation. The study recruited 20 right-handed male
      youths with autism and 20 carefully matched individually, typically developing
      (TD) youths. Microstructural integrity of the left dorsal and left ventral
      pathways responsible for language processing and the functional activation of the
      connected brain regions were investigated by using diffusion spectrum imaging and
      functional magnetic resonance imaging of a semantic task, respectively. Youths
      with autism had significantly poorer language function, and lower functional
      activation in left dorsal and left ventral regions of the language network,
      compared with TD youths. The TD group showed a significant correlation of the
      functional activation of the left dorsal region with microstructural integrity of
      the left ventral pathway, whereas the autism group showed a significant
      correlation of the functional activation of the left ventral region with
      microstructural integrity of the left dorsal pathway, and moreover verbal
      comprehension index was correlated with microstructural integrity of the left
      ventral pathway. These altered structure-function relationships in autism suggest
      possible involvement of the dual pathways in supporting deficient semantic
      processing.

PMID- 23853173
TI  - A look at the polypill story 10 years later.

PMID- 23853171
TI  - Physical presence of nor-binaltorphimine in mouse brain over 21 days after a
      single administration corresponds to its long-lasting antagonistic effect on
      kappa-opioid receptors.
AB  - In the mouse 55 degrees C warm-water tail-withdrawal assay, a single
      administration of nor-binaltorphimine (nor-BNI; 10 mg/kg i.p.) antagonized kappa
      opioid receptor (KOR) agonist-induced antinociception up to 14 days, whereas
      naloxone (10 mg/kg i.p.)-mediated antagonism lasted less than 1 day. In
      saturation binding experiments, mouse brain membranes isolated and washed 1 or 7
      (but not 14) days after nor-BNI administration demonstrated a significant time
      dependent decrease in maximal KOR agonist [(3)H]U69,593 binding. To determine
      whether brain concentrations of nor-BNI were sufficient to explain the antagonism
      of KOR-mediated antinociception, mouse blood and perfused brain were harvested at
      time points ranging from 30 minutes to 21 days after a single administration and
      analyzed for the presence of nor-BNI using liquid chromatography-mass
      spectrometry/mass spectrometry (LC-MS/MS). Nor-BNI was detected in the perfused
      brain homogenate up to 21 days after administration (30 nmol i.c.v. or 10 mg/kg
      i.p.). Subsequent experiments in which nor-BNI was administered at doses
      estimated from the amounts detected in the brain homogenates isolated from
      pretreated mice over time demonstrated significant antagonism of U50,488
      antinociception in a manner consistent with the magnitude of observed KOR
      antagonism. The dose (1.4 nmol) approximating the lowest amount of nor-BNI
      detected in brain on day 14 did not antagonize U50,488-induced antinociception,
      consistent with the absence of U50,488 antagonism observed in vivo at this time
      point after pretreatment. Overall, the physical presence of nor-BNI in the mouse
      brain paralleled its in vivo pharmacological profile, suggesting physicochemical
      and pharmacokinetic properties of nor-BNI may contribute to the prolonged KOR
      antagonism. 

PMID- 23853174
TI  - Inductive and ultrasonic multi-tier interface for low-power, deeply implantable
      medical devices.
AB  - We report the development of a novel multi-tier interface which enables the
      wireless, noninvasive transfer of sufficient amounts of power as well as the
      collection and transmission of data from low-power, deeply implantable analog
      sensors. The interface consists of an inductive coupling subsystem and an
      ultrasonic subsystem. The designed and experimentally verified inductive
      subsystem ensures that 5 W of power is transferred across 10 mm of air gap
      between a single pair of PCB spiral coils with an efficiency of 83% using our
      prototype CMOS logic gate-based driver circuit. The implemented ultrasonic
      subsystem, based on ultrasonic PZT ceramic discs driven in their low-frequency,
      radial/planar-excitation mode, further ensures that 29 MUW of power is delivered
      70 mm deeper inside a homogenous liquid environment-with no acoustic matching
      layer employed-with an efficiency of 1%. Overall system power consumption is 2.3
      W. The implant is intermittently powered every 800 msec; charging a capacitor
      which provides sufficient power for a duration of ~ 18 msec; sufficient for an
      implant MUC operating at a frequency of 500 KHz to transmit a nibble (4 bits) of
      digitized sensed data. 

PMID- 23853175
TI  - Toward a fully integrated neurostimulator with inductive power recovery front
      end.
AB  - In order to investigate new neurostimulation strategies for micturition recovery
      in spinal cord injured patients, custom implantable stimulators are required to
      carry-on chronic animal experiments. However, higher integration of the
      neurostimulator becomes increasingly necessary for miniaturization purposes,
      power consumption reduction, and for increasing the number of stimulation
      channels. As a first step towards total integration, we present in this paper the
      design of a highly-integrated neurostimulator that can be assembled on a 21-mm
      diameter printed circuit board. The prototype is based on three custom integrated
      circuits fabricated in High-Voltage (HV) CMOS technology, and a low-power small
      scale commercially available FPGA. Using a step-down approach where the inductive
      voltage is left free up to 20 V, the inductive power and data recovery front-end
      is fully integrated. In particular, the front-end includes a bridge rectifier, a
      20-V voltage limiter, an adjustable series regulator (5 to 12 V), a switched
      capacitor step-down DC/DC converter (1:3, 1:2, or 2:3 ratio), as well as data
      recovery. Measurements show that the DC/DC converter achieves more than 86% power
      efficiency while providing around 3.9-V from a 12-V input at 1-mA load, 1:3
      conversion ratio, and 50-kHz switching frequency. With such efficiency, the
      proposed step-down inductive power recovery topology is more advantageous than
      its conventional step-up counterpart. Experimental results confirm good overall
      functionality of the system. 

PMID- 23853176
TI  - A magnetic manipulation system using an active filter for electronic detection of
      target cells.
AB  - Important advances in the development of magnetic manipulation devices have been
      recorded over the last few years and promising experimental results have been
      presented. In this article we first perform a detailed analysis on one of most
      widely used magnetic actuators, namely a planar microcoil. Key parameters that
      affect the performance of the actuator are identified and our results are in
      accordance with measured data. Making use of these findings, a lab-on-a-chip
      system is proposed, that also integrates a novel electronic sensing concept for
      live monitoring of its activity. Possible applications of this system include
      highly selective bioseparation or the possibility to manipulate and assemble
      marked particles with great precision. 

PMID- 23853177
TI  - A high-efficiency low-voltage CMOS rectifier for harvesting energy in implantable
      devices.
AB  - We present, in this paper, a new full-wave CMOS rectifier dedicated for
      wirelessly-powered low-voltage biomedical implants. It uses bootstrapped
      capacitors to reduce the effective threshold voltage of selected MOS switches. It
      achieves a significant increase in its overall power efficiency and low voltage
      drop. Therefore, the rectifier is good for applications with low-voltage power
      supplies and large load current. The rectifier topology does not require complex
      circuit design. The highest voltages available in the circuit are used to drive
      the gates of selected transistors in order to reduce leakage current and to lower
      their channel on-resistance, while having high transconductance. The proposed
      rectifier was fabricated using the standard TSMC 0.18 MUm CMOS process. When
      connected to a sinusoidal source of 3.3 V peak amplitude, it allows improving the
      overall power efficiency by 11% compared to the best recently published results
      given by a gate cross-coupled-based structure. 

PMID- 23853178
TI  - A photovoltaic-driven and energy-autonomous CMOS implantable sensor.
AB  - An energy-autonomous, photovoltaic (PV)-driven and MRI-compatible CMOS
      implantable sensor is presented. On-chip P+/N-well diode arrays are used as CMOS
      compatible PV cells to harvest MUW's of power from the light that penetrates into
      the tissue. In this 2.5 mm * 2.5 mm sub-MUW integrated system, the in-vivo
      physiological signals are first measured by using a subthreshold ring oscillator
      based sensor, the acquired data is then modulated into a frequency-shift keying
      (FSK) signal, and finally transmitted neuromorphically to the skin surface by
      using a pair of polarized electrodes. 

PMID- 23853179
TI  - Design of ultra-low power biopotential amplifiers for biosignal acquisition
      applications.
AB  - Rapid development in miniature implantable electronics are expediting advances in
      neuroscience by allowing observation and control of neural activities. The first
      stage of an implantable biosignal recording system, a low-noise biopotential
      amplifier (BPA), is critical to the overall power and noise performance of the
      system. In order to integrate a large number of front-end amplifiers in
      multichannel implantable systems, the power consumption of each amplifier must be
      minimized. This paper introduces a closed-loop complementary-input amplifier,
      which has a bandwidth of 0.05 Hz to 10.5 kHz, an input-referred noise of 2.2 MU
      Vrms, and a power dissipation of 12 MUW. As a point of comparison, a standard
      telescopic-cascode closed-loop amplifier with a 0.4 Hz to 8.5 kHz bandwidth,
      input-referred noise of 3.2 MU Vrms, and power dissipation of 12.5 MUW is
      presented. Also for comparison, we show results from an open-loop complementary
      input amplifier that exhibits an input-referred noise of 3.6 MU Vrms while
      consuming 800 nW of power. The two closed-loop amplifiers are fabricated in a
      0.13 MU m CMOS process. The open-loop amplifier is fabricated in a 0.5 MUm SOI
      BiCMOS process. All three amplifiers operate with a 1 V supply. 

PMID- 23853180
TI  - A multisensor implant for continuous monitoring of intracranial pressure
      dynamics.
AB  - In humans, intracranial pressure (ICP) is not only influenced by pathology, but
      also by orientation in space and body movements. Therefore, it is proposed to
      measure ICP dynamics and body acceleration simultaneously. An algorithm for
      acceleration analysis was developed to monitor orientation in space and allow
      more accurate examination of ICP dynamics during quiet periods. For continuous
      monitoring, an implant was developed and wireless data transmission was
      implemented; this prototype was successfully tested in five pigs. Hydrocephalus
      with increased ICP was experimentally induced in the animals using a surgical
      kaolin infusion. This model of porcine pathology was then tested with the implant
      with the aim for eventual use in humans. ICP dynamics and 2D-acceleration data
      were simultaneously recorded for up to two weeks. This study allowed 24-h
      monitoring and provided analysable data on porcine ICP dynamics with humanlike
      ICP waves, the so called B- and P-waves. Results show that acceleration often had
      a stronger influence on ICP than the amplitudes of the physiological ICP
      characteristics. With test animals in a standing position, without obvious body
      movement, ICP varied to an extent that made the characteristic ICP waves
      difficult to identify. These data allow us to conclude that analysis of both ICP
      and acceleration may be essential for autonomous implants.

PMID- 23853181
TI  - A knowledge-based approach to arterial stiffness estimation using the digital
      volume pulse.
AB  - We have developed a knowledge based approach for arterial stiffness estimation.
      The proposed new approach reliably estimates arterial stiffness based on the
      analysis of age and heart rate normalized reflected wave arrival time. The
      proposed new approach reduces cost, space, technical expertise, specialized
      equipment, complexity, and increases the usability compared to recently
      researched noninvasive arterial stiffness estimators. The proposed method
      consists of two main stages: pulse feature extraction and linear regression
      analysis. The new approach extracts the pulse features and establishes a linear
      prediction equation. On evaluating proposed methodology with pulse wave velocity
      (PWV) based arterial stiffness estimators, the proposed methodology offered the
      error rate of 8.36% for men and 9.52% for women, respectively. With such low
      error rates and increased benefits, the proposed approach could be usefully
      applied as low cost and effective solution for ubiquitous and home healthcare
      environments. 

PMID- 23853182
TI  - Image sensor system with bio-inspired efficient coding and adaptation.
AB  - We designed and implemented an image sensor system equipped with three bio
      inspired coding and adaptation strategies: logarithmic transform, local average
      subtraction, and feedback gain control. The system comprises a field-programmable
      gate array (FPGA), a resistive network, and active pixel sensors (APS), whose
      light intensity-voltage characteristics are controllable. The system employs
      multiple time-varying reset voltage signals for APS in order to realize multiple
      logarithmic intensity-voltage characteristics, which are controlled so that the
      entropy of the output image is maximized. The system also employs local average
      subtraction and gain control in order to obtain images with an appropriate
      contrast. The local average is calculated by the resistive network
      instantaneously. The designed system was successfully used to obtain appropriate
      images of objects that were subjected to large changes in illumination. 

PMID- 23853183
TI  - Spike-timing-dependent plasticity with weight dependence evoked from physical
      constraints.
AB  - Analogue and mixed-signal VLSI implementations of Spike-Timing-Dependent
      Plasticity (STDP) are reviewed. A circuit is presented with a compact
      implementation of STDP suitable for parallel integration in large synaptic
      arrays. In contrast to previously published circuits, it uses the limitations of
      the silicon substrate to achieve various forms and degrees of weight dependence
      of STDP. It also uses reverse-biased transistors to reduce leakage from a
      capacitance representing weight. Chip results are presented showing: various ways
      in which the learning rule may be shaped; how synaptic weights may retain some
      indication of their learned values over periods of minutes; and how distributions
      of weights for synapses convergent on single neurons may shift between more or
      less extreme bimodality according to the strength of correlational cues in their
      inputs. 

PMID- 23853184
TI  - Ewing sarcoma of the adrenal gland: a rare entity.
AB  - A 63-year-old man was referred to our office with an enlarging left adrenal mass
      found on work-up for prostate cancer. Imaging performed over the course of 6
      months demonstrated an increasing left adrenal mass from 2.8 to 3.6 cm.
      Functional testing of the adrenal lesion was performed. The adrenal mass was non
      functional. Owing to the enlarging size, the patient underwent a laparoscopic
      left adrenalectomy without complication and was discharged home the following
      day. Gross pathological evaluation demonstrated a 3.2 cm, well-encapsulated,
      partially cystic mass. Histological evaluation demonstrated a small round blue
      cell tumour suspicious of sarcoma. Immunohistochemical testing revealed strong
      CD99 positivity consistent with Ewing family of tumours. Reverse transcriptase
      PCR demonstrated the presence of the Ewing sarcoma fusion transcript. The patient
      is currently enrolled in an ongoing research chemotherapy protocol at our
      institution using vincristine, doxorubicin, cyclophosphamide, ifosfamide and
      etoposide. 

PMID- 23853185
TI  - Carpal tunnel syndrome due to a plexiform neurofibroma of the median nerve in a
      neurofibromatosis type 1 patient: clinical approach.
AB  - The authors report the case of a 56-year-old male patient with neurofibromatosis
      type 1 (NF1) diagnosed during adolescence and with an insidious clinical
      evolution, characterised by an exuberant cutaneous involvement, referred to the
      orthopaedics outpatient clinic presenting with carpal tunnel syndrome secondary
      to a plexiform neurofibroma of the median nerve. A comprehensive clinical
      approach is discussed, considering the natural history of the disease and its
      potential complications, as well as the lack of consensus regarding standard
      therapeutic options for the compressive peripheral neuropathies in the NF1
      disease. 

PMID- 23853186
TI  - Acute psychosis as a presentation of hypopituitarism.
AB  - Acute onset neuropsychiatric manifestations in hypopituitarism are uncommon. We
      report a case of a 60-year-old man who was a follow-up case of macroprolactinoma
      with hypopituitarism for the last 9 years. He was on medical treatment with
      cabergoline, thyroxine and depot testosterone. During the last 2 years he was non
      adherent to medications especially cabergoline. He was hospitalised for 2 days
      through emergency services following acute onset psychosis. His pituitary hormone
      profile was suggestive of adrenal insufficiency, secondary hypothyroidism and
      hypogonadism. MRI of the hypothalamic pituitary region revealed a pituitary
      macroadenoma which was larger in size compared to the previous scan. Further,
      this lesion was compressing on the adjoining structures including optic chiasma.
      The patient was treated with intravenous fluids, hydrocortisone and thyroxine
      replacement therapy. With this treatment he completely recovered from psychosis
      within 48 h. 

PMID- 23853187
TI  - Testicular epidermoid cysts.

PMID- 23853188
TI  - Acute visceral obstruction.
AB  - Gastric volvulus is a rare cause for acute visceral obstruction, with a high
      mortality rate that rises with delay in definitive treatment. A 33-year-old woman
      with a rare chromosomal mutation (46,XX,del(6)(q25.1q25.3)) presented with
      evidence of acute visceral obstruction. Diagnostic difficulties delayed treatment
      and she clinically deteriorated. Urgent CT imaging revealed acute mesentero-axial
      gastric volvulus. At laparotomy, global failure of colonic and splenic fixation
      was found. The viscera were de-rotated, the stomach salvaged and gastropexy and
      colopexy were performed. This is the first report of gastric volvulus secondary
      to congenital absence of colonic and splenic ligamentous attachments occurring in
      a patient over 30 years of age. This case is interesting not only due to unique
      pathology, but also highlights that general surgeons must be aware of the
      possibility of unusual causes for intestinal obstruction in patients with
      recognised genetic abnormalities, even in adult cases, to avoid harmful
      diagnostic delay. 

PMID- 23853189
TI  - Hepatic visceral larva migrans.
AB  - Visceral larva migrans (VLM) is a systemic manifestation of migration of second
      stage larvae of nematodes through the tissue of human viscera. It is not uncommon
      but is underdiagnosed in developing countries. The liver is the most common organ
      to be involved due to its portal venous blood supply. The imaging findings are
      subtle and differentiation from hepatocellular carcinoma (HCC), metastases,
      cystic mesenchymal hamartoma and granulomatous diseases is difficult. This case
      report highlights the imaging features of hepatic lesions of VLM along with
      clinical and laboratory data which help in clinching the diagnosis. 

PMID- 23853191
TI  - Ring-enhancing lesions in the brain and spinal cord.

PMID- 23853190
TI  - Exsanguinated uterus after massive atonic postpartum haemorrhage.
AB  - This article addresses issues related to pregnancy anaemia and late referral by a
      village birth attendant in resource poor setting in a central state of India. A
      young anaemic woman had labour onset at her village, a birth attendant tried to
      deliver her but failed. When she came to our hospital, had established
      septicaemia and absolutely non-reassurable uterine tone leading to intractable
      atonic postpartum haemorrhage. She died after 5 days because of coagulopathy and
      multiorgan failure. Huge budgets are being spent for the promotion of
      institutional deliveries but still the maternal mortality ratio has not reduced.
      The epidemiology of childbirth, social awareness for safe labour and
      administrative lethargy towards implementation of government programmes have not
      changed. The tertiary care-blood and components-multidisciplinary approach could
      not prevent the death of an anaemic woman. Unless there is a grassroot level
      change in the healthcare delivery system at the village level, the scenario might
      not change. 

PMID- 23853192
TI  - Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple
      neurofibromas of the entire spinal nerve roots.
AB  - The coexistence of polyneuropathy which has the definite clinical and
      electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome
      and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a
      patient with both CMT and NF1, who had multiple neurofibromas involving the
      entire spinal neural axis. In addition, he had multiple neurofibromas distributed
      within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions
      were detected readily by MRI and the patient underwent successful surgical
      resection of the largest tumours compressing bilateral C2 nerve roots. To our
      knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in
      which multiple neurofibromas involved the entire spinal nerve roots. We discuss
      the diagnostic and therapeutic challenges, emphasising the role of MRI and
      electrophysiology in such cases and provide a literature review. 

PMID- 23853193
TI  - Severe eyelid oedema in Graves' ophthalmopathy.
AB  - We report a case of severe eyelid oedema due to Graves' ophthalmopathy (GO). The
      aim was to present a case report and review of the literature about eyelid oedema
      due to GO. The case report includes a history of patient data and literature
      review. The patient was offered intravenous methylprednisolone and gave consent.
      A dosage of 500 mg intravenous methylprednisolone once weekly for 6 weeks,
      followed by 250 mg intravenous methylprednisolone once weekly for 6 weeks, with a
      total treatment period of 12 weeks was given. Up to day, minor improvement has
      been observed. Severe eyelid oedema due to GO is a rare manifestation of Graves'
      disease. In cases of active and moderate-to-severe disease, treatment with
      intravenous glucorticoids is recommended alone or with orbital radiotherapy,
      followed by rehabilitative surgery. 

PMID- 23853194
TI  - A popliteal aneurysm with upper thigh extension: a tip of the iceberg finding.
AB  - A 75-year-old male patient was referred to our orthopaedic department due to
      progressive weakening of the left leg, noticed while going up and down stairs,
      and swelling of the thigh. An increase in swelling was noted in association with
      spicy food. Clinical examination showed a palm-sized non-pulsatile soft mass in
      the popliteal region and swelling in the posterior-lateral thigh. MRI revealed a
      space-occupying 40*15*10 cm mass extending into the upper thigh without
      infiltrating character. Angiography was negative. Open surgical biopsy was
      performed to rule out a soft tissue tumour, during which, connection to the
      popliteal artery was identified. The patient underwent excision of the aneurismal
      sac and a prosthetic graft was interplaced. On follow-up, the patient noticed a
      rapid increase in muscle strength; stairs were no longer a problem. 

PMID- 23853195
TI  - Phantom tumour of the lung.

PMID- 23853196
TI  - Multiple glomuvenous malformations presenting in a child: follow-up over a period
      of 8 years.
AB  - Multiple glomuvenous malformations (GVMs) are a rare condition which usually
      present in children with only a handful of cases reported in the literature. It
      is usually congenital and has an autosomal dominant inheritance pattern. They may
      be distributed throughout the body in either a localised, segmental or
      disseminated pattern. Pain, which is a characteristic feature of glomus tumours,
      is less often associated with GVMs. In addition, unlike glomus tumours which most
      commonly occur over acral skin surfaces, GVMs may occur throughout the body. A
      number of treatment options are available including surgical excision, laser
      treatments and sclerotherapy. We present the case of a 14-year-old boy with
      multiple GVMs which were treated with surgical excision and followed him up over
      a period of 8 years. 

PMID- 23853197
TI  - Relapsing fevers and lymphadenopathy in a young woman.
AB  - A 23-year-old woman presented to the emergency department with severe occipital
      headache, nausea and fever. She was treated with intravenous antibiotics for
      suspected meningitis. After a brief period of response, her symptoms relapsed and
      remained refractory despite continuing intravenous antibiotics for 10 days
      leading to referral to our centre. Physical examination was significant for
      tender right cervical lymph node. Initial tests included pancytopenia, elevated C
      reactive protein, lactate dehydrogenase and unremarkable cerebrospinal fluid.
      Extensive infectious and rheumatology work-up was negative. Massive posterior
      cervical, axillary and inguinal lymphadenopathy was revealed on imaging.
      Excisional biopsy of the deep cervical lymph node showed histiocytic necrotising
      lymphadenitis suggesting a diagnosis of Kikuchi disease. Her course was
      complicated by acute renal failure. Her symptoms resolved in about a week with
      supportive treatment along with improvement in pancytopenia and renal function.
      She had two additional self-limited recurrences in the next 3 months and remains
      symptom free thereafter. 

PMID- 23853198
TI  - Sleep and Wake Classification With ECG and Respiratory Effort Signals.
AB  - We describe a method for the online classification of sleep/wake states based on
      cardiorespiratory signals produced by wearable sensors. The method was conceived
      in view of its applicability to a wearable sleepiness monitoring device. The
      method uses a fast Fourier transform as the main feature extraction tool and a
      feedforward artificial neural network as a classifier. We show that when the
      method is applied to data collected from a single young male adult, the system
      can correctly classify, on average, 95.4% of unseen data from the same user. When
      the method is applied to classify data from multiple users with the same age and
      gender, its accuracy is reduced to 85.3%. However, receiver operating
      characteristic analysis shows that compared to actigraphy, the proposed method
      produces a more balanced correct classification of sleep and wake periods.
      Additionally, by adjusting the classification threshold of the neural classifier,
      86.7% of correct classification is obtained. 

PMID- 23853199
TI  - CTBV Integrated Impulse Radio Design for Biomedical Applications.
AB  - Improving quality of service in wireless communication links is of vital
      importance in biomedical applications. Limitations of current technology are
      evident with a limited number of channels and prone to fading. In this paper, we
      are exploring impulse radio as a feasible technology for health monitoring and
      even as novel detached sensors. By exploring advanced deep submicron technology
      and novel architectures, improved quality of service may be granted. Additional
      interesting biomedical functionality of the impulse radio is detached body
      sensors (short-range medical radar). 

PMID- 23853200
TI  - High-Voltage CMOS Controller for Microfluidics.
AB  - A high-voltage microfluidic controller designed using DALSA semiconductor's 0.8
      mum low-voltage/high-voltage complementary metal-oxide semiconductor/double
      diffused metal-oxide semiconductor process is presented. The chip's four high
      voltage output drivers can switch 300 V, and the dc-dc boost converter can
      generate up to 68 V using external passive components. This integrated circuit
      represents an advancement in microfluidic technology when used in conjunction
      with a charge coupling device (CCD)-based optical system and a glass microfluidic
      channel, enabling a portable and cost-efficient platform for genetic analysis. 

PMID- 23853201
TI  - Handheld Fluorometers for Lab-on-a-Chip Applications.
AB  - We describe the design, fabrication, and performance of a class of simple
      handheld fluorometers. The devices consist of a sensor along with an integrated
      optical filter packaged in a handheld format. The sensor is a differential active
      pixel sensor with in-pixel correlated double sampling fabricated in a 0.5-mu m 2
      poly 3-metal complementary metal-oxide semiconductor process and has a readout
      noise of 175.3 muV, reset noise of 360 muV, dynamic range of 59 dB, and
      conversion gain of 530 nV/e(-) . The filter is a high rejection chromophore
      embedded in a polymer film which is cast onto the chip. We show the results of
      bioassays utilizing two different single color fluorometers constructed by using
      the chromophores 2-(2'-hydroxy 5'-methylphenyl) benzotriazole and Sudan II with
      long-pass wavelengths of 400 nm and 540 nm, respectively. The bioassays measures
      metabolic activity and viability of biological cells, which are useful for
      cytotoxicity and pathogen detection applications. 

PMID- 23853202
TI  - On-body inertial sensing and signal processing for clinical assessment of tremor.
AB  - Tremor, the most common form of movement disorder, is an often debilitating
      condition that adversely affects an individual's ability to maintain functional
      independence. Efforts to study, diagnose, and treat such movement disorders are
      complicated by a dearth of quantitative, precise, or accurate methods for motion
      data collection and assessment. To address this deficiency, this paper provides
      two contributions: 1) the design of a body-area inertial sensing system and 2)
      the evaluation of postcapture, on-body signal-processing algorithms that
      transform sensed inertial data into clinically significant information pertaining
      to tremor symmetry. For the former, we present our technology that meets
      requirements for wearability, fidelity, battery life, and interoperability. For
      the latter, we demonstrate the efficacy of using filter-bank analysis and cross
      correlation to interpret tremor frequency and energy. We extend the previous work
      by presenting a wireless body-area inertial sensing technology and a method to
      reduce, by up to 30 times, the computational demands of cross correlation on such
      a resource-constrained technology. These efforts lay the foundation for real
      time, on-body assessment of tremor as well as more intelligent and energy
      efficient data transmission and storage decisions. 

PMID- 23853203
TI  - An integrated patch-clamp potentiostat with electrode compensation.
AB  - We present the first fully integrated implementation of a patch-clamp measurement
      system with series-access resistance and parasitic capacitive compensation
      capability. The system was implemented in a 0.5- mum silicon-on-sapphire process
      and is capable of recording cell membrane currents up to plusmn20 nA, with an rms
      noise of 5 pA at 10-kHz bandwidth. The system can compensate for the capacitance
      and resistance of the electrode, up to 20 pF and up to 70% of the series-access
      resistance, respectively. The die size is 1150 by 700 mum. The power consumption
      is 300 muW at 3.3 V. The integrated patch-clamp system will be used to fabricate
      high-throughput planar patch-clamp systems. 

PMID- 23853204
TI  - Investigation of cadmium pollution in contaminated industrial area in Guilan
      province industrial estates.
AB  - Toxicity and accumulation of cadmium in body organs by eating contaminated food
      has an important role in endangering a human's health. Using Environmental
      Protection Agency (EPA) reports, site 1, site 2 and site 3 were selected as
      polluted sites and site 4 was selected as the control site. Seedlings of
      buttonwood were prepared for 12 months then root, stem, and leaf samples were
      harvested and the amounts of cadmium element in stem and leaf organs together
      with the growth parameters were measured. This study determines the amount of
      cadmium accumulated in Platanus occidentalis. The respective cadmium
      concentrations in the root, leaf, and stem in site 1 were 382, 98, and 87; in
      site 2 they were 591, 122, and 94; and in site 3 they were 633, 151, and 104
      mg/kg dry weight (DW). Furthermore, the comparison between accumulation and
      transfer of cadmium in the study showed more absorption of this metal by the root
      than that by the stem and leaf. The result of this research shows that buttonwood
      has the potential for cadmium accumulation without any serious damage to its
      growth. To control the extent of contamination in industrial areas, petrochemical
      industries, power plants and vast contaminated municipal areas, there is a great
      need for planting plants like buttonwood. 

PMID- 23853205
TI  - Reply to Luehr and Etz.

PMID- 23853206
TI  - The polysaccharide inulin is characterized by an extensive series of periodic
      isoforms with varying biological actions.
AB  - In studying the molecular basis for the potent immune activity of previously
      described gamma and delta inulin particles and to assist in production of inulin
      adjuvants under Good Manufacturing Practice, we identified five new inulin
      isoforms, bringing the total to seven plus the amorphous form. These isoforms
      comprise the step-wise inulin developmental series amorphous -> alpha-1 (AI-1) ->
      alpha-2 (AI-2) -> gamma (GI) -> delta (DI) -> zeta (ZI) -> epsilon (EI) -> omega
      (OI) in which each higher isoform can be made either by precipitating dissolved
      inulin or by direct conversion from its precursor, both cases using regularly
      increasing temperatures. At higher temperatures, the shorter inulin polymer
      chains are released from the particle and so the key difference between isoforms
      is that each higher isoform comprises longer polymer chains than its precursor.
      An increasing trend of degree of polymerization is confirmed by end-group
      analysis using (1)H nuclear magnetic resonance spectroscopy. Inulin isoforms were
      characterized by the critical temperatures of abrupt phase-shifts
      (solubilizations or precipitations) in water suspensions. Such (aqueous)
      "melting" or "freezing" points are diagnostic and occur in strikingly periodic
      steps reflecting quantal increases in noncovalent bonding strength and increments
      in average polymer lengths. The (dry) melting points as measured by modulated
      differential scanning calorimetry similarly increase in regular steps. We
      conclude that the isoforms differ in repeated increments of a precisely repeating
      structural element. Each isoform has a different spectrum of biological
      activities and we show the higher inulin isoforms to be more potent alternative
      complement pathway activators. 

PMID- 23853207
TI  - Teen dating violence: building a research program through collaborative insights.
AB  - The National Institute of Justice (NIJ) has an emerging portfolio of research in
      the area of teen dating violence (also known as adolescent relationship abuse).
      This article begins with a discussion of the developments that prompted NIJ to
      focus on teen dating violence. Next, the article highlights specific
      accomplishments and contributions that NIJ has made to helping develop knowledge
      and scientific understanding of adolescent relationship abuse, particularly
      around the prevention of teen dating violence perpetration and victimization.
      This is followed by a presentation of some of the key findings from NIJ-funded
      research. We then move to a discussion of some of the complex issues around
      definition, measurement and research methods and how NIJ has been involved in
      addressing those issues. The article concludes with some thoughts about the
      intersection of teen dating violence research, policy, and practice and
      highlights several research gaps that are in need of additional attention.

PMID- 23853208
TI  - Tobacco smoke exposure and the risk of childhood acute lymphoblastic and myeloid
      leukemias by cytogenetic subtype.
AB  - BACKGROUND: Tobacco smoke contains carcinogens known to damage somatic and germ
      cells. We investigated the effect of tobacco smoke on the risk of childhood acute
      lymphoblastic leukemia (ALL) and myeloid leukemia (AML), especially subtypes of
      prenatal origin such as ALL with translocation t(12;21) or high-hyperdiploidy (51
      67 chromosomes). METHODS: We collected information on exposures to tobacco
      smoking before conception, during pregnancy, and after birth in 767 ALL cases,
      135 AML cases, and 1,139 controls (1996-2008). Among cases, chromosome
      translocations, deletions, or aneuploidy were identified by conventional
      karyotype and fluorescence in situ hybridization. RESULTS: Multivariable
      regression analyses for ALL and AML overall showed no definite evidence of
      associations with self-reported (yes/no) parental prenatal active smoking and
      child's passive smoking. However, children with history of paternal prenatal
      smoking combined with postnatal passive smoking had a 1.5-fold increased risk of
      ALL [95% confidence interval (CI), 1.01-2.23], compared to those without smoking
      history (ORs for pre- or postnatal smoking only were close to one). This joint
      effect was seen for B-cell precursor ALL with t(12;21) (OR = 2.08; 95% CI, 1.04
      4.16), but not high hyperdiploid B-cell ALL. Similarly, child's passive smoking
      was associated with an elevated risk of AML with chromosome structural changes
      (OR = 2.76; 95% CI, 1.01-7.58), but not aneuploidy. CONCLUSIONS: Our data suggest
      that exposure to tobacco smoking was associated with increased risks of childhood
      ALL and AML; and risks varied by timing of exposure (before and/or after birth)
      and cytogenetic subtype, based on imprecise estimates. IMPACT: Parents should
      limit exposures to tobacco smoke before and after the child's birth.

PMID- 23853210
TI  - Higher free thyroxine levels are associated with all-cause mortality in euthyroid
      older men: the Health In Men Study.
AB  - OBJECTIVE: Thyroid dysfunction predicts poorer health outcomes, but the
      relationship between thyroid hormone levels within the reference range and
      mortality in older adults remains unclear. In this study, we examined the
      associations between the concentrations of free thyroxine (FT4) and TSH and all
      cause mortality in older men without thyroid disease. SUBJECTS AND METHODS: We
      performed a longitudinal study in community-dwelling men aged 70-89 years. Men
      with thyroid disease or taking thyroid-related medications were excluded.
      Baseline FT4 and TSH levels were assayed. Incident deaths were ascertained using
      data linkage. RESULTS: There were 3885 men without thyroid disease followed for
      (means.d.) 6.41.5 years, during which time 837 had died (21.5%). men who had died
      had higher baseline ft4 levels (16.22.3 vs 15.82.1 pmol/l, p0.001), but
      comparable tsh levels (2.41.5 vs 2.31.5 miu/l, P=0.250). After accounting for
      age, smoking, physical factors and medical comorbidities, higher circulating ft4
      levels predicted all-cause mortality (quartile Q4 vs quartiles Q1Q3: FT4 levels
      >= 17.32 vs <17.32 pmol/l: adjusted hazard ratio (HR)=1.19, 95% CI=1.02-1.39,
      P=0.025). TSH levels did not predict mortality. After excluding men with
      subclinical hyperthyroidism or hypothyroidism, there were 3442 men and 737 who
      had died (21.4%). In these men, higher FT4 levels remained independently
      associated with all-cause mortality (quartile Q4 vs quartiles Q1-Q3: adjusted
      HR=1.19, 95% CI=1.02-1.41, P=0.032). CONCLUSIONS: Higher FT4 levels are
      associated with all-cause mortality in euthyroid older men, independently of
      conventional risk factors and medical comorbidities. Additional research is
      needed to determine whether or not this relationship is causal and to clarify the
      utility of thyroid function testing to stratify mortality risk in ageing men.

PMID- 23853209
TI  - Diagnostic chest X-rays and breast cancer risk before age 50 years for BRCA1 and
      BRCA2 mutation carriers.
AB  - BACKGROUND: The effects of low-dose medical radiation on breast cancer risk are
      uncertain, and few studies have included genetically susceptible women, such as
      those who carry germline BRCA1 and BRCA2 mutations. METHODS: We studied 454 BRCA1
      and 273 BRCA2 mutation carriers ages younger than 50 years from three breast
      cancer family registries in the United States, Canada, and Australia/New Zealand.
      We estimated breast cancer risk associated with diagnostic chest X-rays by
      comparing mutation carriers with breast cancer (cases) with those without breast
      cancer (controls). Exposure to chest X-rays was self-reported. Mammograms were
      not considered in the analysis. RESULTS: After adjusting for known risk factors
      for breast cancer, the ORs for a history of diagnostic chest X-rays, excluding
      those for tuberculosis or pneumonia, were 1.16 [95% confidence interval (CI),
      0.64-2.11] for BRCA1 mutations carriers and 1.22 (95% CI, 0.62-2.42) for BRCA2
      mutations carriers. The OR was statistically elevated for BRCA2 mutation carriers
      with three to five diagnostic chest X-rays (P = 0.01) but not for those with six
      or more chest X-rays. Few women reported chest fluoroscopy for tuberculosis or
      chest X-rays for pneumonia; the OR estimates were elevated, but not statistically
      significant, for BRCA1 mutation carriers. CONCLUSIONS: Our findings do not
      support a positive association between diagnostic chest X-rays and breast cancer
      risk before the ages of 50 years for BRCA1 or BRCA2 mutation carriers. IMPACT:
      Given the increasing use of diagnostic imaging involving higher ionizing
      radiation doses, further studies of genetically predisposed women are warranted.

PMID- 23853211
TI  - Comparison of detection and miss rates of narrow band imaging, flexible spectral
      imaging chromoendoscopy and white light at screening colonoscopy: a randomised
      controlled back-to-back study.
AB  - OBJECTIVE: Virtual chromoendoscopy (CE) is expected to enhance adenoma yield and
      reduce variation in performance between colonoscopists. This study aimed to
      compare the efficacy of narrow band imaging (NBI), flexible spectral imaging CE
      (FICE) and white light (WL) colonoscopy and their impact for less experienced
      endoscopists. METHODS: We performed a randomised tandem colonoscopy trial
      controlling for withdrawal time and bowel preparation. Average-risk adults
      undergoing screening colonoscopy were enrolled and randomly assigned to first
      withdrawal with one of the three imaging modalities (NBI (NBI-WL group), FICE
      (FICE-WL group) and WL (WL-WL group)). Eight colonoscopists were categorised into
      expert and non-expert subgroups. RESULTS: 1650 subjects (mean age 51.4 years,
      63.9% men) were included (550 in each group). Compared with WL, neither NBI nor
      FICE increased the mean number of adenomas detected per patient (0.37 vs 0.35 and
      0.36; p=0.591) or the percentage of patients with adenoma (25.3% vs 24.5% and
      23.6%; p=0.753). For all three modalities, expert subgroups had higher yields of
      adenomas than non-expert subgroups. Learning curves were observed only for non
      expert subgroups with all three modalities. The percentage of missed adenomas did
      not differ between the three groups (20.8% by WL vs 22.9% by NBI and 26.0% by
      FICE, p=0.300) and was not affected by endoscopists' expertise. CONCLUSIONS:
      Neither NBI nor FICE improved adenoma detection or miss rates, with no difference
      in diagnostic efficacy between the two systems. Virtual CE had no additional
      benefits over WL for non-experts. CLINICAL TRIAL REGISTRATION NUMBER: KCT0000570.

PMID- 23853212
TI  - Body-centered, mixed, but not hand-centered coding of visual targets in the
      medial posterior parietal cortex during reaches in 3D space.
AB  - The frames of reference used by neurons in posterior parietal cortex (PPC) to
      encode spatial locations during arm reaching movements is a debated topic in
      modern neurophysiology. Traditionally, target location, encoded in retinocentric
      reference frame (RF) in caudal PPC, was assumed to be serially transformed to
      body-centered and then hand-centered coordinates rostrally. However, recent
      studies suggest that these transformations occur within a single area. The caudal
      PPC area V6A has been shown to represent reach targets in eye-centered, body
      centered, and a combination of both RFs, but the presence of hand-centered coding
      has not been yet investigated. To examine this issue, 141 single neurons were
      recorded from V6A in 2 Macaca fascicularis monkeys while they performed a
      foveated reaching task in darkness. The targets were presented at different
      distances and lateralities from the body and were reached from initial hand
      positions located at different depths. Most V6A cells used body-centered, or
      mixed body- and hand-centered coordinates. Only a few neurons used pure hand
      centered coordinates, thus clearly distinguishing V6A from nearby PPC regions.
      Our findings support the view of a gradual RF transformation in PPC and also
      highlight the impact of mixed frames of reference. 

PMID- 23853214
TI  - A mixed-signal multichip neural recording interface with bandwidth reduction.
AB  - We present a multichip structure assembled with a medical-grade stainless-steel
      microelectrode array intended for neural recordings from multiple channels. The
      design features a mixed-signal integrated circuit (IC) that handles conditioning,
      digitization, and time-division multiplexing of neural signals, and a digital IC
      that provides control, bandwidth reduction, and data communications for telemetry
      toward a remote host. Bandwidth reduction is achieved through action potential
      detection and complete capture of waveforms by means of onchip data buffering.
      The adopted architecture uses high parallelism and low-power building blocks for
      safety and long-term implantability. Both ICs are fabricated in a CMOS 0.18-mum
      process and are subsequently mounted on the base of the microelectrode array. The
      chips are stacked according to a vertical integration approach for better
      compactness. The presented device integrates 16 channels, and is scalable to
      hundreds of recording channels. Its performance was validated on a testbench with
      synthetic neural signals. The proposed interface presents a power consumption of
      138 muW per channel, a size of 2.30 mm(2), and achieves a bandwidth reduction
      factor of up to 48 with typical recordings. 

PMID- 23853215
TI  - Peptide mass fingerprinting using field-programmable gate arrays.
AB  - The reconfigurable computing paradigm, which exploits the flexibility and
      versatility of field-programmable gate arrays (FPGAs), has emerged as a powerful
      solution for speeding up time-critical algorithms. This paper describes a
      reconfigurable computing solution for processing raw mass spectrometric data
      generated by MALDI-TOF instruments. The hardware-implemented algorithms for
      denoising, baseline correction, peak identification, and deisotoping, running on
      a Xilinx Virtex-2 FPGA at 180 MHz, generate a mass fingerprint that is over 100
      times faster than an equivalent algorithm written in C, running on a Dual 3-GHz
      Xeon server. The results obtained using the FPGA implementation are virtually
      identical to those generated by a commercial software package MassLynx. 

PMID- 23853213
TI  - Update on the epidemiology of gastro-oesophageal reflux disease: a systematic
      review.
AB  - OBJECTIVE: To update the findings of the 2005 systematic review of population
      based studies assessing the epidemiology of gastro-oesophageal reflux disease
      (GERD). DESIGN: PubMed and Embase were screened for new references using the
      original search strings. Studies were required to be population-based, to include
      >= 200 individuals, to have response rates >= 50% and recall periods <12 months.
      GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or
      according to the Montreal definition, or diagnosed by a clinician. Temporal and
      geographic trends in disease prevalence were examined using a Poisson regression
      model. RESULTS: 16 studies of GERD epidemiology published since the original
      review were found to be suitable for inclusion (15 reporting prevalence and one
      reporting incidence), and were added to the 13 prevalence and two incidence
      studies found previously. The range of GERD prevalence estimates was 18.1%-27.8%
      in North America, 8.8%-25.9% in Europe, 2.5%-7.8% in East Asia, 8.7%-33.1% in the
      Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000
      person-years was approximately 5 in the overall UK and US populations, and 0.84
      in paediatric patients aged 1-17 years in the UK. Evidence suggests an increase
      in GERD prevalence since 1995 (p<0.0001), particularly in North America and East
      Asia. CONCLUSIONS: GERD is prevalent worldwide, and disease burden may be
      increasing. Prevalence estimates show considerable geographic variation, but only
      East Asia shows estimates consistently lower than 10%.

PMID- 23853216
TI  - Factor graph-based biomolecular circuit analysis for designing forward error
      correcting biosensors.
AB  - We previously reported the fabrication and the verification of novel biomolecular
      transistors where electrical conductivity of a ldquopolyaniline nanowiresrdquo
      channel is controlled by antigen-antibody interactions. In this paper, we present
      a simulation framework for analyzing the reliability of biosensor circuits
      constructed by using these biomolecular transistors. At the core of the proposed
      framework is a library of electrical circuit models that capture the stochastic
      interaction between biomolecules and their variability to environmental
      conditions and experimental protocols. Reliability analysis is then performed by
      exploiting probabilistic dependencies between multiple circuit elements by using
      a factor graph-based decoding technique. The proposed computational approach
      facilitates rapid evaluation of forward error correction (FEC) strategies for
      biosensors without resorting to painstaking and time-consuming experimental
      procedures. The analysis presented in this paper shows that an asymmetric FEC
      biosensor code outperforms a repetition FEC biosensor code which has been
      proposed for microarray technology. In addition, we also show that the proposed
      analysis leads to a novel ldquoco-detectionrdquo protocol that could be used for
      reliable detection of trace quantities of pathogens. 

PMID- 23853217
TI  - Amperometric electrochemical microsystem for a miniaturized protein biosensor
      array.
AB  - Protein-based bioelectrochemical interfaces offer great potential for rapid
      detection, continuous use, and miniaturized sensor arrays. This paper introduces
      a microsystem platform that enables multiple bioelectrochemical interfaces to be
      interrogated simultaneously by an onchip amperometric readout system. A post
      complementary metal-oxide semiconductor (CMOS) fabrication procedure is described
      that permits the formation of planar electrode arrays and self assembly of
      biosensor interfaces on the electrodes. The onchip, 0.5-mum CMOS readout
      electronics include a compact potentiostat that supports a very broad range of
      input currents-6 pA to 10 muA-to accommodate diverse biosensor interfaces. The
      2.3 times 2.2-mm chip operates from a 5-V supply at 0.6 mA. A prototype
      electrochemical sensor platform, including an onchip potentiostat and
      miniaturized biosensor array, was characterized by using cyclic voltammetry. The
      linear relationship between the oxidization peak values and the concentrations of
      target analytes in the solution verifies functionality of the system and
      demonstrates the potential for future implementations of this platform in high
      sensitivity, low cost, and onchip protein-based sensor arrays. 

PMID- 23853218
TI  - A wireless-implantable microsystem for continuous blood glucose monitoring.
AB  - A remotely powered implantable microsystem for continuous blood glucose
      monitoring is presented. The microsystem consists of a microfabricated glucose
      biosensor flip-chip bonded to a transponder chip. The transponder chip is
      inductively powered by an external reader with a 13.56-MHz carrier. It then
      measures the output signal of the glucose biosensor and transmits the measured
      data back to the external reader using load-shift keying (LSK). The microsystem
      has a volume of 32 mm(3). The procedures for the microfabrication of the glucose
      sensor and the assembly of the microsystem are described along with the
      description of the circuit blocks of the transponder chip. The transponder chip
      has been fabricated with the TSMC 0.18-mum CMOS process and has a total area of
      1.3 x 1.3 mm(2). The chip can measure the sensor output current ranging from 1 nA
      to 1 muA with less than 0.3% nonlinearity error, provided that the amplitude of
      the received RF signal is higher than 2.6 V; the circuit consumes a total current
      of about 110 muA. 

PMID- 23853219
TI  - A remote compact sensor for the real-time monitoring of human heartbeat and
      respiration rate.
AB  - A remote compact sensor system for the detection of human vital signs (heartbeat
      and respiration rate) is presented. The frequency band of 24 GHz is employed for
      remote sensing. For the compact size, the developed sensor uses a circularly
      polarized electromagnetic wave with a single antenna. The sensor system is
      composed of radio-frequency circuits, a signal conditioning block, a data
      acquisition unit, and a signal-processing part. The peak detection of the power
      spectral density with a tracking algorithm is utilized for the real-time
      detection of human vital signs. The measurement result is compared with the
      commercial fingertip sensor. The comparison result shows excellent agreement. 

PMID- 23853220
TI  - Spontaneous recanalization of an occluded middle cerebral artery in a patient
      with moyamoya.
AB  - Moyamoya disease is a rare cerebrovascular disorder that is characterized by
      progressive stenosis of the distal portion of the internal carotid artery and its
      main branches. Here the authors present the first case of spontaneous
      recanalization of an occluded middle cerebral artery in a woman with moyamoya who
      had not undergone surgical or endovascular treatment. Although the exact
      mechanisms remain unclear, spontaneous recanalization in moyamoya could be
      considered a possible phenomenon. Thus, the neurosurgeons should always pay
      attention to the pathological variety of dynamic changes in the cerebrovascular
      structure in moyamoya. 

PMID- 23853221
TI  - Patency in arteriovenous grafts in hemodialysis patients.
AB  - OBJECTIVE: It is difficult to maintain a working access for patients on
      hemodialysis. Despite current Dialysis Outcome Quality Initiatives
      recommendations of "Fistula First," not everyone qualifies for a fistula, and
      those patients undergoing the alternative treatment, a graft, can experience
      graft failure. This study examines factors associated with arteriovenous graft
      (AVG) patency. METHODS: A retrospective analysis was completed for all the
      patients who had an AVG during 2005 to 2010. Data were collected from electronic
      medical records, including date of first and subsequent interventions, salvage
      technique (surgical vs percutaneous), medical comorbidities, and use of
      antiplatelet medications (aspirin and clopidogrel). Continuous variables were
      compared with 2 sample t tests, and categorical variables with chi-square/Fisher
      exact test. Logistic regression was used to determine the odds ratio for risk
      factors associated with patency. A P value of <.05 was considered significant.
      All analyses were done using SAS 9.2 (SAS Institute Inc, Cary, North Carolina).
      RESULTS: A total of 193 unique patients had an AVG. Of the 193 patients, 64% were
      female, 83% were hypertensive, and 64% were diabetic. The locations of the grafts
      were 80% arm, 15% forearm, and 5% thigh. Configurations, including loop and
      straight, were 34% and 63%, respectively. Comorbidities were not associated with
      patency. Primary patency was not found to be different with respect to location
      and configuration of graft and type of intervention. Primary patency for patients
      taking only aspirin (n = 43) and only clopidogrel (n = 17) were significantly
      different from patients on a combination of aspirin and clopidogrel (n = 7), with
      a P = .0051 and P = .0447, respectively. CONCLUSION: Neither location nor
      configuration affects the primary patency of AVGs. Aspirin alone is not inferior
      to aspirin and clopidogrel. Further prospective studies may be warranted to
      establish a consensus regarding medications and patency with AVGs.

PMID- 23853222
TI  - An analysis of the factors influencing radiation dose and fluoroscopic time
      during renal artery stent placement.
AB  - PURPOSE: To determine the factors that affect mean absorbed dose and fluoroscopic
      times during renal artery stent placement. MATERIALS AND METHODS: After
      institutional review board approval, the HI-IQ database was queried for patients
      undergoing renal artery stent placement only from January 2007 to June 2010.
      Procedures that were performed as part of other procedures such as iliac artery
      stents were excluded. The HI-IQ data included fluoroscopy time (f) and radiation
      dose (mGy). Demographic, medical history, procedural details, and advanced
      preprocedural renal artery stent imaging were obtained. Variables (number of
      stents, average body mass index , number of stents placed per year and number of
      years' service of an interventional physician, pre-procedural imaging, and use of
      embolic protection device) were analyzed using a t test after log transformation
      and testing for variance with an F test. RESULTS: A total of 134 patients (75
      males, 70.6 +/- 10.5 years old) underwent the placement of 177 renal artery
      stents (unilateral [n = 95], average stent per patient = 1.3). Mean fluoroscopy
      time was 15.6 minutes and mean absorbed dose to the patient was 1729 mGy. The
      average fluoroscopic time and absorbed dose was significantly higher with
      bilateral stent placement compared to unilateral placement (13.8 vs 19.7 minutes,
      P = .002; 1803 vs 2380 mGy, P = .03). The average fluoroscopic time was
      significantly higher in patients undergoing abdominal aortogram prior to renal
      artery selection and stent placement. CONCLUSION: The placement of more than 1
      stent with an abdominal angiogram prior to renal artery stent placement results
      in increased fluoroscopic time and mean absorbed dose.

PMID- 23853223
TI  - Vascular access outcome in the elderly dialysis patient in combination with the
      quality of life.
AB  - PURPOSE: We performed a retrospective study on hemodialysis fistulae in patients
      aged 75 years and older. METHODS: Dialysis records of 2 hospitals were searched
      for patients of 75 years and older who had primary autologous radiocephalic
      arteriovenous fistulae (RCAVFs) and brachiocephalic arteriovenous fistulae
      (BCAVFs). Outcome measures were primary, primary-assisted, and secondary patency
      rates. Also, quality of life (QOL) was measured. RESULTS: A total of 107 fistulae
      were placed in 90 patients; 65 (61%) RCAVFs and 42 (39%) BCAVFs were created. The
      primary patency rate (P = .026) and the primary-assisted patency rate (P = .016)
      of BCAVFs were significantly higher than that of RCAVFs. Secondary patency rates
      at 1 year (P = .01) and 2 years (P = .035) were higher in BCAVFs than in RCAVFs.
      CONCLUSIONS: The BCAVFs give significantly higher primary and primary-assisted
      patency rates and also significantly higher secondary patency rates at 1 and 2
      years. Therefore, we suggest the placement of elbow fistulae in the elderly
      patients. The QOL was surprisingly high in this population despite a high
      mortality rate.

PMID- 23853224
TI  - Longitudinal outcomes after tibioperoneal angioplasty alone compared to tibial
      stenting and atherectomy for critical limb ischemia.
AB  - OBJECTIVES: There are limited data available evaluating longitudinal outcomes
      after tibioperoneal angioplasty (TA) alone compared to adjunctive tibial
      procedures including stenting and atherectomy. METHODS: Using the Centers for
      Medicare & Medicaid Services inpatient claims (2005-2007), patients evaluated TA
      only, TA plus stent placement (TA + S), and TA plus atherectomy (TA + A).
      RESULTS: A total of 2080 patients with critical limb ischemia underwent
      percutaneous tibioperoneal intervention for the indication of ulceration.
      Procedures included TA (56.3%), TA + S (16.2%), and TA + A (27.5%). Rates of
      amputation were not statistically different between the groups at 30, 90, and 365
      days after the intervention. Mean total hospital charges were TA ($35,867), TA +
      A ($41,698; P = .0004), and TA + S ($51,040; P < .0001). CONCLUSIONS: Patients
      undergoing TA alone compared to concomitant stenting or atherectomy for
      ulceration demonstrated no improvement in limb salvage. Future analysis of
      adjunctive tibioperoneal interventions is essential to temper cost, as they fail
      to improve long-term limb salvage.

PMID- 23853225
TI  - Endovascular versus medical therapy for uncomplicated type B aortic dissection: a
      qualitative review.
AB  - BACKGROUND: Uncomplicated type B dissections have been traditionally managed with
      antihypertensive therapy. In the endovascular era, this dictum has been
      revisited. This review pooled the available studies to compare the outcomes of
      best medical therapy (BMT) to thoracic endovascular aortic repair (TEVAR) for
      uncomplicated type B dissections. METHODS: A literature search was performed to
      identify studies on uncomplicated type B dissections managed with BMT with and
      without TEVAR. The primary outcome measures were mortality rates at 30 days and
      at 2 years following intervention. RESULTS: A total of 6 studies included 123
      patients who underwent TEVAR/BMT, and 566 patients who had BMT alone. The
      mortality rates at 30 days (6.5% TEVAR/BMT vs 4.8% BMT, P = .21) and at 2 years
      (9.7% vs 11.9%, P = .32) were similar. Renal failure was greater in TEVAR/BMT
      (15.4% vs 2.1%, P < .01). Rates of surgical reintervention/intervention were
      similar (17.6% vs 20.1%, P = .31). CONCLUSION: The TEVAR with BMT does not
      provide survival benefit compared to BMT alone, 2 years following uncomplicated
      type B aortic dissection.

PMID- 23853226
TI  - Popliteal artery entrapment syndrome: ultrasound imaging, intraoperative
      findings, and clinical outcome.
AB  - OBJECTIVES: The purpose of this study was to report our experience with popliteal
      artery entrapment syndrome (PAES) with special emphasis on the applicability of
      duplex ultrasound scanning (DUS) when diagnosing PAES. In addition to examining
      the correlation between DUS and intraoperative findings in symptomatic limbs, the
      ultrasonic effect of plantar flexion in healthy volunteers were also evaluated.
      METHODS: During a 12-month period, 11 symptomatic limbs in 8 patients with a mean
      age of 29 years were referred with suspected PAES and enrolled consecutively. The
      popliteal artery was studied preoperatively with DUS in rest and during active
      plantar flexion. The popliteal artery was explored in all symptomatic limbs, and
      the intraoperative findings served as gold standard. Additionally, the popliteal
      arteries in 11 healthy volunteers (22 limbs) were evaluated with DUS during rest
      and plantar flexion. RESULTS: Intraoperative findings confirmed PAES in all 11
      symptomatic limbs in accordance with the preoperative DUS examination. Surgical
      release of the popliteal artery was performed in 11 limbs. At a median follow-up
      of 15 months, all 11 limbs were free of ischemic symptoms and regained normalized
      popliteal flow on DUS. In the 22 symptom-free limbs, DUS showed normal popliteal
      flow during both rest and plantar flexion. CONCLUSIONS: In this series of
      patients with surgically confirmed PAES, we found preoperative DUS to have
      perfect agreement with the intraoperative findings in diagnosing PAES. The
      applicability of the method seems to be emphasized by the restoration of
      popliteal flow and relief of arterial insufficiency after surgical release in all
      patients, and by the fact, that none of the healthy volunteers were able to
      compress the popliteal artery during plantar flexion.

PMID- 23853227
TI  - A 4 MUW/Ch analog front-end module with moderate inversion and power-scalable
      sampling operation for 3-D neural microsystems.
AB  - We report an analog front-end prototype designed in 0.25 MUm CMOS process for
      hybrid integration into 3-D neural recording microsystems. For scaling towards
      massive parallel neural recording, the prototype has investigated some critical
      circuit challenges in power, area, interface, and modularity. We achieved
      extremely low power consumption of 4 MUW/channel, optimized energy efficiency
      using moderate inversion in low-noise amplifiers (K of 5.98 * 108 or NEF of 2.9),
      and minimized asynchronous interface (only 2 per 16 channels) for command and
      data capturing. We also implemented adaptable operations including programmable
      gain amplification, power-scalable sampling (up to 50 kS/s/channel), wide
      configuration range (9-bit) for programmable gain and bandwidth, and 5-bit site
      selection capability (selecting 16 out of 128 sites). The implemented front-end
      module has achieved a reduction in noise-energy-area product by a factor of 5-25
      times as compared to the state-of-the-art analog front-end approaches reported to
      date.

PMID- 23853228
TI  - Towards a smart experimental arena for long-term electrophysiology experiments.
AB  - Wireless power and data transmission have created promising prospects in
      biomedical research by enabling perpetual data acquisition and stimulation
      systems. We present a work in progress towards such a system, called the
      EnerCage, equipped with scalable arrays of overlapping planar spiral coils (PSC)
      and 3-axis magnetic sensors for focused wireless power transmission to randomly
      moving targets, such as small freely behaving animal subjects. The EnerCage
      system includes a stationary unit for 3D non-line-of-sight localization and
      inductive power transmission through a geometrically optimized PSC array. The
      localization algorithm compares the magnetic sensor outputs with a threshold to
      activate a PSC. All PSCs are optimized based on the worst-case misalignment,
      considering parasitics from the overlapping and adjacent PSCs. EnerCage also has
      a mobile unit attached to or implanted in the subject's body, which includes a
      permanent magnetic tracer for localization and back telemetry circuit for
      efficient closed-loop inductive power regulation. The EnerCage system is designed
      to enable long-term electrophysiology experiments on freely behaving small animal
      subjects in large experimental arenas without requiring them to carry bulky
      batteries. A prototype of the EnerCage system with five PSCs and five magnetic
      sensors achieved power transfer efficiency (PTE) of 19.6% at the worst-case
      horizontal misalignment of 49.1 mm (?1/3 of the PSC radius) and coupling distance
      of 78 mm with a mobile unit coil, 20 mm in radius. The closed-loop power
      management mechanism maintains the mobile unit received power at 20 mW despite
      misalignments, tilting, and distance variations up to a maximum operating height
      of 120 mm (PTE = 5%).

PMID- 23853229
TI  - A battery-free multichannel digital neural/EMG telemetry system for flying
      insects.
AB  - This paper presents a digital neural/EMG telemetry system small enough and
      lightweight enough to permit recording from insects in flight. It has a measured
      flight package mass of only 38 mg. This system includes a single-chip telemetry
      integrated circuit (IC) employing RF power harvesting for battery-free operation,
      with communication via modulated backscatter in the UHF (902-928 MHz) band. An on
      chip 11-bit ADC digitizes 10 neural channels with a sampling rate of 26.1 kSps
      and 4 EMG channels at 1.63 kSps, and telemeters this data wirelessly to a base
      station. The companion base station transceiver includes an RF transmitter of +36
      dBm (4 W) output power to wirelessly power the telemetry IC, and a digital
      receiver with a sensitivity of -70 dBm for 10-5 BER at 5.0 Mbps to receive the
      data stream from the telemetry IC. The telemetry chip was fabricated in a
      commercial 0.35 MU m 4M1P (4 metal, 1 poly) CMOS process. The die measures 2.36 *
      1.88 mm, is 250 MUm thick, and is wire bonded into a flex circuit assembly
      measuring 4.6 * 6.8 mm.

PMID- 23853230
TI  - A miniaturized platform for laser speckle contrast imaging.
AB  - Imaging the brain in animal models enables scientists to unravel new biological
      insights. Despite critical advancements in recent years, most laboratory imaging
      techniques comprise of bulky bench top apparatus that require the imaged animals
      to be anesthetized and immobilized. Thus, animals are imaged in their non-native
      state severely restricting the scope of behavioral experiments. To address this
      gap, we report a miniaturized microscope that can be mounted on a rat's head for
      imaging in awake and unrestrained conditions. The microscope uses laser speckle
      contrast imaging (LSCI), a high resolution yet wide field imaging modality for
      imaging blood vessels and perfusion. Design details of both the image formation
      and acquisition modules are presented. A Monte Carlo simulation was used to
      estimate the depth of tissue penetration achievable by the imaging system while
      the produced speckle Airy disc patterns were simulated using Fresnel's
      diffraction theory. The microscope system weighs only 7 g and occupies less than
      5 cm3 and was successfully used to generate proof of concept LSCI images of rat
      brain vasculature. We validated the utility of the head-mountable system in an
      awake rat brain model by confirming no impairment to the rat's native behavior.

PMID- 23853231
TI  - Design constraints for mobile, high-speed fluorescence brain imaging in awake
      animals.
AB  - In this paper we present a fully self-contained imaging instrument (30 mm overall
      length) that is capable of recording high speed and detect relatively small
      fluorescent signals (0.1% DeltaF/F) from brain tissues potentially containing
      genetically-encoded sensors or dyes. This device potentially enables the study of
      neuronal activity in awake and mobile animals during natural behaviors without
      the stress and suppression of anesthesia and restraint. The device is a fully
      self-contained illumination system, wide field fluorescence microscope (~ 4.8 mm2
      FOV-25 um lateral resolution-1.8 * magnification-0.39 NA) and CMOS image sensor
      (32 * 32). The total weight of the system is 10 g and is capable of imaging up to
      900 fps. We present voltage dye RH1692 experiments using the system to study the
      somatosensory cortex of mice during whisker movements using an air puff.

PMID- 23853232
TI  - An analog integrated circuit beamformer for high-frequency medical ultrasound
      imaging.
AB  - We designed and fabricated a dynamic receive beamformer integrated circuit (IC)
      in 0.35-MUm CMOS technology. This beamformer IC is suitable for integration with
      an annular array transducer for high-frequency (30-50 MHz) intravascular
      ultrasound (IVUS) imaging. The beamformer IC consists of receive preamplifiers,
      an analog dynamic delay-and-sum beamformer, and buffers for 8 receive channels.
      To form an analog dynamic delay line we designed an analog delay cell based on
      the current-mode first-order all-pass filter topology, as the basic building
      block. To increase the bandwidth of the delay cell, we explored an enhancement
      technique on the current mirrors. This technique improved the overall bandwidth
      of the delay line by a factor of 6. Each delay cell consumes 2.1-mW of power and
      is capable of generating a tunable time delay between 1.75 ns to 2.5 ns. We
      successfully integrated the fabricated beamformer IC with an 8-element annular
      array. Experimental test results demonstrated the desired buffering,
      preamplification and delaying capabilities of the beamformer. 

PMID- 23853233
TI  - 16-channel CMOS impedance spectroscopy DNA analyzer with dual-slope multiplying
      ADCs.
AB  - We present a 16-channel, mixed-signal CMOS DNA analyzer that utilizes frequency
      response analysis (FRA) to extract the real and imaginary impedance components of
      the biosensor. Two computationally intensive operations, the multiplication and
      integration required by the FRA algorithm, are performed by an in-channel dual
      slope multiplying ADC in the mixed-signal domain resulting in minimal area and
      power consumption. Multiplication of the input current by a digital coefficient
      is implemented by modulating the counter-controlled duration of the charging
      phase of the ADC. Integration is implemented by accumulating output digital bits
      in the ADC counter over multiple input samples. The 1.05 mm*1.6 mm prototype
      fabricated in a 0.13 MUm standard CMOS technology has been validated in prostate
      cancer DNA detection. Each channel occupies an area of only 0.06 mm2 and consumes
      42 MUW of power from a 1.2 V supply.

PMID- 23853234
TI  - New approaches for carbon nanotubes-based biosensors and their application to
      cell culture monitoring.
AB  - Amperometric biosensors are complex systems and they require a combination of
      technologies for their development. The aim of the present work is to propose a
      new approach in order to develop nanostructured biosensors for the real-time
      detection of multiple metabolites in cell culture flasks. The fabrication of five
      Au working electrodes onto silicon substrate is achieved with CMOS compatible
      microtechnology. Each working electrode presents an area of 0.25 mm2, so
      structuration with carbon nanotubes and specific functionalization are carried
      out by using spotting technology, originally developed for microarrays and DNA
      printing. The electrodes are characterized by cyclic voltammetry and compared
      with commercially available screen-printed electrodes. Measurements are carried
      out under flow conditions, so a simple fluidic system is developed to guarantee a
      continuous flow next to the electrodes. The working electrodes are functionalized
      with different enzymes and calibrated for the real-time detection of glucose,
      lactate, and glutamate. Finally, some tests are performed on surnatant
      conditioned medium sampled from neuroblastoma cells (NG-108 cell line) to detect
      glucose and lactate concentration after 72 hours of cultivation. The developed
      biosensor for real-time and online detection of multiple metabolites shows very
      promising results towards circuits and systems for cell culture monitoring.

PMID- 23853235
TI  - A 0.35 MUm sub-ns wake-up time ON-OFF switchable LVDS driver-receiver chip I/O
      pad pair for rate-dependent power saving in AER bit-serial links.
AB  - This paper presents a low power switchable current mode driver/receiver I/O pair
      for high speed serial transmission of asynchronous address event representation
      (AER) information. The sparse nature of AER packets (also called events) allows
      driver/receiver bias currents to be switched off to save power. The on/off times
      must be lower than the bit time to minimize the latency introduced by the
      switching mechanism. Using this technique, the link power consumption can be
      scaled down with the event rate without compromising the maximum system
      throughput. The proposed technique has been implemented on a typical push/pull
      low voltage differential signaling (LVDS) circuit, but it can easily be extended
      to other widely used current mode standards, such as current mode logic (CML) or
      low-voltage positive emitter-coupled logic (LVPECL). A proof of concept prototype
      has been fabricated in 0.35 MUm CMOS incorporating the proposed driver/receiver
      pair along with a previously reported switchable serializer/deserializer scheme.
      At a 500 Mbps bit rate, the maximum event rate is 11 Mevent/s for 32-bit events.
      In this situation, current consumption is 7.5 mA and 9.6 mA for the driver and
      receiver, respectively, while differential voltage amplitude is +/-300 mV.
      However, if event rate is lower than 20-30 Kevent/s, current consumption has a
      floor of 270 MUA for the driver and 570 MUA for the receiver. The measured ON/OFF
      switching times are in the order of 1 ns. The serial link could be operated at up
      to 710 Mbps bit rate, resulting in a maximum 32-bit event rate of 15 Mevent/s .
      This is the same peak event rate as that obtained with the same SerDes circuits
      and a non-switched driver/receiver pair. 

PMID- 23853236
TI  - Multichannel bipotentiostat integrated with a microfluidic platform for
      electrochemical real-time monitoring of cell cultures.
AB  - An electrochemical detection system specifically designed for multi-parameter
      real-time monitoring of stem cell culturing/differentiation in a microfluidic
      system is presented. It is composed of a very compact 24-channel electronic
      board, compatible with arrays of microelectrodes and coupled to a microfluidic
      cell culture system. A versatile data acquisition software enables performing
      amperometry, cyclic voltammetry and impedance spectroscopy in each of the 12
      independent chambers over a 100 kHz bandwidth with current resolution down to 5
      pA for 100 ms measuring time. The design of the platform, its realization and
      experimental characterization are reported, with emphasis on the analysis of
      impact of input capacitance (i.e., microelectrode size) and microfluidic pump
      operation on current noise. Programmable sequences of successive injections of
      analytes (ferricyanide and dopamine) and rinsing buffer solution as well as the
      impedimetric continuous tracking for seven days of the proliferation of a colony
      of PC12 cells are successfully demonstrated. 

PMID- 23853237
TI  - A 0.09 MUW low power front-end biopotential amplifier for biosignal recording.
AB  - This work presents a biopotential front-end amplifier in which the MOS
      transistors are biased in subthreshold region with a supply voltage and current
      of 0.4-0.8 V and 0.23-1.86 MUA, respectively, to reduce the system power. Flicker
      noise is then removed using a chopping technique, and differential interference
      produced by electrode impedance imbalance is suppressed using a Gm-C filter.
      Additionally, the circuit is fabricated using TSMC 0.18 MUm CMOS technology with
      a core area of 0.77 * 0.36 mm2. With a minimum supply voltage of 0.4 V, the
      measured SNR and power consumption of the proposed IC chip are 54.1 dB and
      0.09MUW, respectively.

PMID- 23853238
TI  - The application of a multi-parameter analysis in choosing the location of a new
      solid waste landfill in Serbia.
AB  - This article presents a process of evaluation and selection of the most
      favourable location for a sanitary landfill facility from three alternative
      locations, by applying a multi-criteria decision-making (MCDM) method. An
      incorrect choice of location for a landfill facility can have a significant
      negative economic and environmental impact, such as the pollution of air, ground
      and surface waters. The aim of this article is to present several improvements in
      the practical process of landfill site selection using the VIKOR MCDM compromise
      ranking method integrated with a fuzzy analytic hierarchy process approach for
      determining the evaluation criteria weighing coefficients. The VIKOR method
      focuses on ranking and selecting from a set of alternatives in the presence of
      conflicting and non-commensurable (different units) criteria, and on proposing a
      compromise solution that is closest to the ideal solution. The work shows that
      valuable site ranking lists can be obtained using the VIKOR method, which is a
      suitable choice when there is a large number of relevant input parameters. 

PMID- 23853240
TI  - Microfluidic system for controlled gelation of a thermally reversible hydrogel.
AB  - The integration of cell culture and characterization onto a miniaturized platform
      promises to benefit many applications such as tissue engineering, drug screening,
      and those involving small, precious cell populations. This paper presents the
      controlled on-chip gelation of a thermally-reversible hydrogel. Channel design
      and flowrate control are crucial in determining hydrogel geometry, while
      integrated temperature control triggers reversible gel formation. Formation of
      hydrogel droplets through shearing of immiscible flows is demonstrated with
      subsequent on-chip gelation. The temperature of phase transition occurs between
      32degC-34degC, well within the range for mammalian cell encapsulation and
      culture. 

PMID- 23853239
TI  - Development of demand forecasting tool for natural resources recouping from
      municipal solid waste.
AB  - Sustainable waste management requires an integrated planning and design strategy
      for reliable forecasting of waste generation, collection, recycling, treatment
      and disposal for the successful development of future residential precincts. The
      success of the future development and management of waste relies to a high extent
      on the accuracy of the prediction and on a comprehensive understanding of the
      overall waste management systems. This study defies the traditional concepts of
      waste, in which waste was considered as the last phase of production and
      services, by putting forward the new concept of waste as an intermediate phase of
      production and services. The study aims to develop a demand forecasting tool
      called 'zero waste index' (ZWI) for measuring the natural resources recouped from
      municipal solid waste. The ZWI (ZWI demand forecasting tool) quantifies the
      amount of virgin materials recovered from solid waste and subsequently reduces
      extraction of natural resources. In addition, the tool estimates the potential
      amount of energy, water and emissions avoided or saved by the improved waste
      management system. The ZWI is tested in a case study of waste management systems
      in two developed cities: Adelaide (Australia) and Stockholm (Sweden). The ZWI of
      waste management systems in Adelaide and Stockholm is 0.33 and 0.17 respectively.
      The study also enumerates per capita energy savings of 2.9 GJ and 2.83 GJ,
      greenhouse gas emissions reductions of 0.39 tonnes (CO2e) and 0.33 tonnes (CO2e),
      as well as water savings of 2.8 kL and 0.92 kL in Adelaide and Stockholm
      respectively.

PMID- 23853241
TI  - Progress in chip-scale photonic sensing.
AB  - Chip-scale integrated planar photonic sensing systems for portable diagnostics
      and monitoring are emerging, as photonic components are integrated into systems
      with silicon (Si), Si complementary metal-oxide semiconductor, and fluidics. This
      paper reviews progress in these areas. Medical and environmental applications,
      candidate photonic sensors, integration methodologies, integrated subsystem
      demonstrations, and challenges facing this emerging field are discussed in this
      paper. 

PMID- 23853242
TI  - Micro-Organism-on-Chip: Emerging Direct-Write CMOS-Based Platform for Biological
      Applications.
AB  - We describe the emerging applications of direct-write CMOS-based lab-on-chip
      which consists of capacitive sensors integrated with microfluidic structures. The
      microfluidic components are implemented through direct-write microfabrication
      process (DWFP) on a variety of substrates including integrated circuits. We put
      forward the recent advances of DWFP for different applications while our focus is
      placed on biological testing through a novel on-chip capacitive measurement
      method. We thereafter reveal the viability of this approach for biosensing
      purposes by demonstrating and discussing the experimental results on micro
      organisms. These results are in full agreement with the bio-interface model and
      other features presented throughout the paper. 

PMID- 23853243
TI  - QRS Detection Based on Multiscale Mathematical Morphology for Wearable ECG
      Devices in Body Area Networks.
AB  - A novel wearable electrocardiograph (ECG) QRS detection algorithm for wearable
      ECG devices in body area networks is presented in this paper, which utilizes the
      multistage multiscale mathematical morphology filtering to suppress the impulsive
      noise and uses the multiframe differential modulus accumulation to remove the
      baseline drift and enhance the signal. The proposed algorithm, verified with data
      from the MIT/BIH Arrhythmia Database and wearable ECG devices, achieves an
      average QRS detection rate of 99.61%, a sensitivity of 99.81%, and a positive
      prediction of 99.80%. It compares favorably to the published methods. 

PMID- 23853244
TI  - Sensor layer of a multiparameter single-point integrated system.
AB  - Microfabrication and circuit integration provide sensors with reduced size,
      improved performance, increased reliability, and lower cost. These microsensors
      can measure a variety of properties and behaviors, and are typically constructed
      on a range of substrate materials in combination with signal conditioning,
      information processing, and data-communication electronics. The challenge remains
      to integrate multiple sensors, each measuring different parameters with separate
      supporting electronics, into a single. high-density microsystem. We describe a
      multiple parameter medical sensor that is suitable for mounting on an active
      moving patient where mechanical flexibility, tight adhesion, lightweight, small
      size, and biocompatibility of an easily applied flat stick-on assembly at a
      single skin site are important considerations. Traditional microintegration
      technologies, such as system-in-package and system-on-chip, typically create
      lumped aggregations of components. In this paper, the flat architectural platform
      of a multiparameter sensor system is presented with microcircuitry distributed
      across multiple stacked layers that can be easily bent to fit body contours. The
      silicone-encapsulated fabrication of a thin foldable polyimide substrate with
      distributed surface-mount electronics is demonstrated. The measured performance
      results are discussed with a particular focus on the assessment of vibration
      sensing elements after integration into this type of system has been described. 

PMID- 23853245
TI  - Fault modeling and functional test methods for digital microfluidic biochips.
AB  - Dependability is an important attribute for microfluidic biochips that are used
      for safety-critical applications, such as point-of-care health assessment, air
      quality monitoring, and food-safety testing. Therefore, these devices must be
      adequately tested after manufacture and during bioassay operations. Known
      techniques for biochip testing are all function oblivious (i.e., while they can
      detect and locate defect sites on a microfluidic array, they cannot be used to
      ensure correct operation of functional units). In this paper, we introduce the
      concept of functional testing of microfluidic biochips. We address fundamental
      biochip operations, such as droplet dispensing, droplet transportation, mixing,
      splitting, and capacitive sensing. Long electrode actuation times are avoided to
      ensure that there is no electrode degradation during testing. The functional
      testing of pin-constrained biochips is also studied. We evaluate the proposed
      test methods using simulations as well as experiments for a fabricated biochip. 

PMID- 23853246
TI  - Neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or paclitaxel in
      early stage breast cancer and evaluation of betaIII-tubulin expression as a
      predictive marker.
AB  - BACKGROUND: This randomized phase II trial was designed to compare the rate of
      pathologic complete response (pCR) induced by neoadjuvant cyclophosphamide plus
      doxorubicin (AC) followed by ixabepilone or paclitaxel in women with early stage
      breast cancer (BC). Expression of betaIII-tubulin as a predictive marker was also
      evaluated. PATIENTS AND METHODS: Women with untreated, histologically confirmed
      primary invasive breast adenocarcinoma received four cycles of AC followed by 1:1
      randomization to either ixabepilone 40 mg/m2 (3-hour infusion) every 3 weeks for
      four cycles (n = 148) or weekly paclitaxel 80 mg/m2 (1-hour infusion) for 12
      weeks (n = 147). All patients underwent a core needle biopsy of the primary
      cancer for molecular marker analysis prior to chemotherapy. betaIII-Tubulin
      expression was assessed using immunohistochemistry. RESULTS: There was no
      significant difference in the rate of pCR in the ixabepilone treatment arm
      (24.3%; 90% confidence interval [CI], 18.6-30.8) and the paclitaxel treatment arm
      (25.2%; 90% CI, 19.4-31.7). betaIII-Tubulin-positive patients obtained higher pCR
      rates compared with betaIII-tubulin-negative patients in both treatment arms;
      however, betaIII-tubulin expression was not significantly associated with a
      differential response to ixabepilone or paclitaxel. The safety profiles of both
      regimens were generally similar, although neutropenia occurred more frequently in
      the ixabepilone arm (grade 3/4: 41.3% vs. 8.4%). The most common nonhematologic
      toxicity was peripheral neuropathy. CONCLUSIONS: Neoadjuvant treatment of early
      stage BC with AC followed by ixabepilone every 3 weeks or weekly paclitaxel was
      well tolerated with no significant difference in efficacy. Higher response rates
      were observed among betaIII-tubulin-positive patients.

PMID- 23853250
TI  - Response to: should we give long-term macrolide therapy for COPD?

PMID- 23853248
TI  - Uptake of neonatal BCG vaccination in England: performance of the current policy
      recommendations.
AB  - BCG uptake among infants in England has not been measured since targeted infant
      vaccination replaced universal schoolchildren vaccination in 2005, mainly because
      of the challenges in defining denominators. We estimated uptake between 2006 and
      2008 by dividing number of BCG doses administered to infants by number of all
      live births (where BCG vaccination is universal) or ethnic minority/Eastern
      Europeans live births (where infant-BCG vaccination is selective). Weighted
      average uptake was 68% (95% CI 65% to 71%), slightly higher in primary care
      trusts with universal (72% (95% CI 64% to 80%)) than selective (66% (95% CI 61%
      to 70%)) policy; and also 13% higher in areas vaccinating in postnatal wards
      compared with community settings. 

PMID- 23853251
TI  - 'Action. Adventure. Special offers.': How Marlboro engages consumers on its
      website.

PMID- 23853247
TI  - Genomic alterations in advanced esophageal cancer may lead to subtype-specific
      therapies.
AB  - The development of targeted agents for metastatic esophageal or gastroesophageal
      junction (GEJ) tumors has been limited when compared with that for other common
      tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2)
      antibody, trastuzumab, in combination with chemotherapy, is the only approved
      novel agent for these cancers, and its use is limited to the small population of
      patients whose tumors overexpress HER-2. Despite recent progress in the field,
      median overall survival remains only 8-12 months for patients with stage IV
      esophageal or GEJ cancer. In this article, we examine the molecular aberrations
      thought to drive the development and spread of esophageal cancer and identify
      promising targets for specific tumor inhibition. Data from clinical studies of
      targeted agents are reviewed, including epidermal growth factor receptor
      antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth
      factor-directed therapy. Current and future targets include MET, fibroblast
      growth factor receptor, and immune-based therapies. Evidence from trials to date
      suggests that molecularly unselected patient cohorts derive minimal benefit from
      most target-specific agents, suggesting that future collaborative investigation
      should focus on preselected molecular subgroups of patients with this challenging
      heterogeneous disease. 

PMID- 23853253
TI  - A mm-sized wirelessly powered and remotely controlled locomotive implant.
AB  - A wirelessly powered and controlled implantable device capable of locomotion in a
      fluid medium is presented. Two scalable low-power propulsion methods are
      described that achieve roughly an order of magnitude better performance than
      existing methods in terms of thrust conversion efficiency. The wireless prototype
      occupies 0.6 mm * 1 mm in 65 nm CMOS with an external 2 mm * 2 mm receive
      antenna. The IC consists of a matching network, a rectifier, a bandgap reference,
      a regulator, a demodulator, a digital controller, and high-current drivers that
      interface directly with the propulsion system. It receives 500 MUW from a 2 W
      1.86 GHz power signal at a distance of 5 cm. Asynchronous pulse-width modulation
      on the carrier allows for data rates from 2.5-25 Mbps with energy efficiency of
      0.5 pJ/b at 10 Mbps. The received data configures the propulsion system drivers,
      which are capable of driving up to 2 mA at 0.2 V and can achieve speed of 0.53
      cm/sec in a 0.06 T magnetic field. 

PMID- 23853252
TI  - Russia SimSmoke: the long-term effects of tobacco control policies on smoking
      prevalence and smoking-attributable deaths in Russia.
AB  - BACKGROUND: Russia has high smoking rates and weak tobacco control policies. A
      simulation model is used to examine the effect of tobacco control policies on
      past and future smoking prevalence and premature mortality in Russia. METHODS:
      The Russia model was developed using the SimSmoke tobacco control model
      previously developed for the USA and other nations. The model inputs population
      size, birth, death and smoking rates specific to Russia. It assesses,
      individually and in combination, the effect of seven types of policies consistent
      with the WHO Framework Convention on Tobacco Control (FCTC): taxes, smoke-free
      air, mass media campaign, advertising bans, warning labels, cessation treatment
      and youth access policies. Outcomes are smoking prevalence and the number of
      smoking-attributable deaths by age and gender from 2009 to 2055. RESULTS:
      Increasing cigarette taxes to 70% of retail price, stronger smoke-free air laws,
      a high-intensity media campaign and comprehensive treatment policies are each
      potent policies to reduce smoking prevalence and smoking-attributable premature
      deaths in Russia. With the stronger set of policies, the model estimates that,
      relative to the status quo trend, smoking prevalence can be reduced by as much as
      30% by 2020, with a 50% reduction projected by 2055. This translates into 2 684
      994 male and 1 011 985 female premature deaths averted from 2015-2055.
      CONCLUSIONS: SimSmoke results highlight the relative contribution of policies to
      reducing the tobacco health burden in Russia. Significant inroads to reducing
      smoking prevalence and premature mortality can be achieved through strengthening
      tobacco control policies in line with FCTC recommendations.

PMID- 23853254
TI  - A sub-10 nA DC-balanced adaptive stimulator IC with multi-modal sensor for
      compact electro-acupuncture stimulation.
AB  - A compact electro-acupuncture (EA) system is proposed for a multi-modal feedback
      EA treatment. It is composed of a needle, a compact EA patch, and an
      interconnecting conductive thread. The 3 cm diameter compact EA patch is
      implemented with an adaptive stimulator IC and a small coin battery on the planar
      fashionable circuit board (P-FCB) technology. The adaptive stimulator IC can form
      a closed current loop for even a single needle, and measure the electromyography
      (EMG) and the skin temperature to analyze the stimulation status as well as
      supply programmable stimulation current (40 MUA-1 mA) with 5 different modes. The
      large time constant (LTC) sample and hold (S/H) current matching technique
      achieves the high-precision charge balancing ( <;10 nA) for the patient's safety.
      The measured data can be wirelessly transmitted to the external EA analyzer
      through the body channel communication (BCC) transceiver for the low power
      consumption. The external EA analyzer can show the patient's status, such as the
      muscle fatigue and the change of the skin temperature. Based on these analyses,
      the practitioner can adaptively change the stimulation parameters for the optimal
      treatment value. A 12.5 mm(2) 0.13 MUm RF CMOS stimulator chip consumes 6.8 mW at
      1.2 V supporting 32 different current levels. The proposed compact EA system is
      fully implemented and tested on the human body. 

PMID- 23853255
TI  - Power-efficient oscillator-based readout circuit for multichannel resonant
      volatile sensors.
AB  - This work presents a multichannel electronic nose system that enables a range of
      novel applications owing to high sensitivity, low form factor and low power
      consumption. Each channel is based on a combination of doubly-clamped
      piezoelectric MEMS resonators and CMOS oscillator-based readout designed in TSMC
      0.25 MUm technology. Using "application specific" polymer coatings, the
      individual resonators can be tuned to detect mixtures of volatile organic
      compounds (VOCs). This system achieves ppm-level theoretical limit of detection
      for ethanol which paves the way towards a broad range of applications such as
      personalized health and environment air quality. 

PMID- 23853256
TI  - A 160 MUA biopotential acquisition IC with fully integrated IA and motion
      artifact suppression.
AB  - This paper proposes a 3-channel biopotential monitoring ASIC with simultaneous
      electrode-tissue impedance measurements which allows real-time estimation of
      motion artifacts on each channel using an an external MUC. The ASIC features a
      high performance instrumentation amplifier with fully integrated sub-Hz HPF
      rejecting rail-to-rail electrode-offset voltages. Each readout channel further
      has a programmable gain amplifier and programmable 4th order low-pass filter.
      Time-multiplexed 12 b SAR-ADCs are used to convert all the analog data to
      digital. The ASIC achieves >; 115 dB of CMRR (at 50/60 Hz), a high input
      impedance of >; 1 GOmega and low noise (1.3 MUVrms in 100 Hz). Unlike traditional
      methods, the ASIC is capable of actual motion artifact suppression in the analog
      domain before final amplification. The complete ASIC core operates from 1.2 V
      with 2 V digital IOs and consumes 200 MUW when all 3 channels are active. 

PMID- 23853257
TI  - A high-throughput time-resolved mini-silicon photomultiplier with embedded
      fluorescence lifetime estimation in 0.13 MUm CMOS.
AB  - We describe a miniaturized, high-throughput, time-resolved fluorescence lifetime
      sensor implemented in a 0.13 m CMOS process, combining single photon detection,
      multiple channel timing and embedded pre-processing of fluorescence lifetime
      estimations on a single device. Detection is achieved using an array of single
      photon avalanche diodes (SPADs) arranged in a digital silicon photomultiplier
      (SiPM) architecture with 400 ps output pulses and a 10% fill-factor. An array of
      time-to-digital converters (TDCs) with ~50 ps resolution records up to 8 photon
      events during each excitation period. Data from the TDC array is then processed
      using a centre-of-mass method (CMM) pre-calculation to produce fluorescence
      lifetime estimations in real-time. The sensor is believed to be the first
      reported implementation of embedded fluorescence lifetime estimation. The system
      is demonstrated in a practical laboratory environment with measurements of a
      variety of fluorescent dyes with different single exponential lifetimes,
      successfully showing the sensor's ability to overcome the classic pile-up
      limitation of time-correlated single photon counting (TCSPC) by over an order of
      magnitude. 

PMID- 23853258
TI  - A wireless magnetoresistive sensing system for an intraoral tongue-computer
      interface.
AB  - Tongue drive system (TDS) is a tongue-operated, minimally invasive, unobtrusive,
      and wireless assistive technology (AT) that infers users' intentions by detecting
      their voluntary tongue motion and translating them into user-defined commands.
      Here we present the new intraoral version of the TDS (iTDS), which has been
      implemented in the form of a dental retainer. The iTDS system-on-a-chip (SoC)
      features a configurable analog front-end (AFE) that reads the magnetic field
      variations inside the mouth from four 3-axial magnetoresistive sensors located at
      four corners of the iTDS printed circuit board (PCB). A dual-band transmitter
      (Tx) on the same chip operates at 27 and 432 MHz in the
      Industrial/Scientific/Medical (ISM) band to allow users to switch in the presence
      of external interference. The Tx streams the digitized samples to a custom
      designed TDS universal interface, built from commercial off-the-shelf (COTS)
      components, which delivers the iTDS data to other devices such as smartphones,
      personal computers (PC), and powered wheelchairs (PWC). Another key block on the
      iTDS SoC is the power management integrated circuit (PMIC), which provides
      individually regulated and duty-cycled 1.8 V supplies for sensors, AFE, Tx, and
      digital control blocks. The PMIC also charges a 50 mAh Li-ion battery with
      constant current up to 4.2 V, and recovers data and clock to update its
      configuration register through a 13.56 MHz inductive link. The iTDS SoC has been
      implemented in a 0.5-MUm standard CMOS process and consumes 3.7 mW on average. 

PMID- 23853259
TI  - A 0.83- MUW QRS detection processor using quadratic spline wavelet transform for
      wireless ECG acquisition in 0.35- MUm CMOS.
AB  - Healthcare electronics count on the effectiveness of the on-patient signal
      preprocessing unit to moderate the wireless data transfer for better power
      efficiency. In order to reduce the system power in long-time ECG acquisition,
      this work describes an on-patient QRS detection processor for arrhythmia
      monitoring. It extracts the concerned ECG part, i.e., the RR-interval between the
      QRS complex for evaluating the heart rate variability. The processor is
      structured by a scale-3 quadratic spline wavelet transform followed by a maxima
      modulus recognition stage. The former is implemented via a symmetric FIR filter,
      whereas the latter includes a number of feature extraction steps: zero-crossing
      detection, peak (zero-derivative) detection, threshold adjustment and two finite
      state machines for executing the decision rules. Fabricated in 0.35-MUm CMOS the
      300-Hz processor draws only 0.83 MUW, which is favorably comparable with the
      prior arts. In the system tests, the input data is placed via an on-chip 10-bit
      SAR analog-to-digital converter, while the output data is emitted via an off-the
      shelf wireless transmitter (TI CC2500) that is configurable by the processor for
      different data transmission modes: 1) QRS detection result, 2) raw ECG data or 3)
      both. Validated with all recordings from the MIT-BIH arrhythmia database, 99.31%
      sensitivity and 99.70% predictivity are achieved. Mode 1 with solely the result
      of QRS detection exhibits 6* reduction of system power over modes 2 and 3. 

PMID- 23853260
TI  - Development of unconstrained heartbeat and respiration measurement system with
      pneumatic flow.
AB  - The management of health through daily monitoring of heartbeat and respiration
      signals is of major importance for early diagnosis to prevent diseases of the
      respiratory and circulatory system. However, such daily health monitoring is
      possible only if the monitoring system is physically and psychologically
      noninvasive. In this paper, an unconstrained method of measuring heartbeat and
      respiration signals, by using a thermistor to measure the air flows from the air
      mattress to an air tube accompanying the subject's heartbeat and respiration, is
      proposed. The SN ratio with interference by opening and closing of a door as
      environmental noise was compared with that obtained by the conventional condenser
      microphone method. As a result, the SN ratios with the condenser microphone
      method were 26.6 +/- 4.2 dB for heartbeat and 27.8 +/- 3.0 dB for respiration,
      whereas with the proposed method they were 34.9 +/- 3.1 dB and 42.1 +/- 2.5 dB,
      respectively. 

PMID- 23853261
TI  - Modeling of the cell-electrode interface noise for microelectrode arrays.
AB  - Microelectrodes are widely used in the physiological recording of cell field
      potentials. As microelectrode signals are generally in the MUV range,
      characteristics of the cell-electrode interface are important to the recording
      accuracy. Although the impedance of the microelectrode-solution interface has
      been well studied and modeled in the past, no effective model has been
      experimentally verified to estimate the noise of the cell-electrode interface.
      Also in existing interface models, spectral information is largely disregarded.
      In this work, we developed a model for estimating the noise of the cell-electrode
      interface from interface impedances. This model improves over existing noise
      models by including the cell membrane capacitor and frequency dependent
      impedances. With low-noise experiment setups, this model is verified by
      microelectrode array (MEA) experiments with mouse muscle myoblast cells.
      Experiments show that the noise estimated from this model has <;10% error, which
      is much less than estimations from existing models. With this model, noise of the
      cell-electrode interface can be estimated by simply measuring interface
      impedances. This model also provides insights for micro- electrode design to
      achieve good recording signal-to-noise ratio. 

PMID- 23853262
TI  - A multichannel EEG acquisition scheme based on single ended amplifiers and
      digital DRL.
AB  - Single ended (SE) amplifiers allow implementing biopotential front-ends with a
      reduced number of parts, being well suited for preamplified electrodes or compact
      EEG headboxes. On the other hand, given that each channel has independent gain;
      mismatching between these gains results in poor common-mode rejection ratios
      (CMRRs) (about 30 dB considering 1% tolerance components). This work proposes a
      scheme for multichannel EEG acquisition systems based on SE amplifiers and a
      novel digital driven right leg (DDRL) circuit, which overcome the poor CMRR of
      the front-end stage providing a high common mode reduction at power line
      frequency (up to 80 dB). A functional prototype was built and tested showing the
      feasibility of the proposed technique. It provided EEG records with negligible
      power line interference, even in very aggressive EMI environments. 

PMID- 23853263
TI  - Differential expression of long noncoding RNAs in the livers of female B6C3F1
      mice exposed to the carcinogen furan.
AB  - The mammalian genome is transcribed into mRNAs that code for protein and a broad
      spectrum of other noncoding (nc) RNA products. Long ncRNAs (lncRNA), defined as
      ncRNA species > 200 nucleotides long, are emerging as important epigenetic
      regulators of gene expression that are involved in a spectrum of biological
      processes of relevance to toxicology. We conducted a gene expression profiling
      study in the livers of female B6C3F1 mice exposed to the carcinogen furan at 0.0,
      1.0, and 2.0mg/kg (noncarcinogenic doses) and at 4.0 and 8.0mg/kg (carcinogenic
      doses) for 3 weeks. LncRNA differential expression showed a nonlinear dose
      response with none differentially expressed at 1.0 or 2.0mg/kg, 2 lncRNAs at
      4.0mg/kg furan, and 83 at 8mg/kg, representing 13.3% (83/632) of the total number
      of differentially expressed transcripts. Among the lncRNAs observed, two lncRNAs
      examined showed transcriptional clustering with nearby protein-coding genes.
      LincRNA-p21 is an antisense transcript that is 15kb downstream from Cdkn1a locus
      and appears to be cotranscribed with the protein coding gene Cdkn1a at 8.0mg/kg
      furan. In a separate independent study, RNA samples from the livers of mice
      administered benzo(a)pyrene also demonstrated increased levels of Cdkn1a and the
      antisense lincRNA-p21 transcript. These data demonstrate that lncRNAs are
      transcriptional targets of furan exposures associated with levels of furan that
      are cytotoxic and induce cell proliferation. In addition, certain lncRNA
      transcripts are associated with the expression of nearby coding protein genes. We
      hypothesize that lncRNAs have potential as epigenetic biomarkers of carcinogenic
      exposures. 

PMID- 23853264
TI  - Polarization-Analyzing CMOS Image Sensor With Monolithically Embedded Polarizer
      for Microchemistry Systems.
AB  - This paper proposes and demonstrates a polarization-analyzing CMOS sensor based
      on image sensor architecture. The sensor was designed targeting applications for
      chiral analysis in a microchemistry system. The sensor features a monolithically
      embedded polarizer. Embedded polarizers with different angles were implemented to
      realize a real-time absolute measurement of the incident polarization angle.
      Although the pixel-level performance was confirmed to be limited, estimation
      schemes based on the variation of the polarizer angle provided a promising
      performance for real-time polarization measurements. An estimation scheme using
      180 pixels in a 1deg step provided an estimation accuracy of 0.04deg.
      Polarimetric measurements of chiral solutions were also successfully performed to
      demonstrate the applicability of the sensor to optical chiral analysis. 

PMID- 23853265
TI  - CMOS Baseline Tracking and Cancellation Instrumentation for Nanoparticle-Coated
      Chemiresistors.
AB  - Chemiresistor (CR) sensors and sensor arrays coated with thiolate-monolayer
      protected gold nanoparticle (MPN) interfaces show great promise as detectors in
      gas-chromatographic microsystems with applications in biomedical and
      environmental analysis including breath biomarkers of disease. This paper
      describes a new readout circuit that overcomes the wide range of baseline
      resistances and drift in baseline values inherent to MPN-coated CRs to achieve a
      57 ppm readout resolution. The 0.5-mum CMOS circuit operates at 5 V and provides
      a response resolution of 74 muV. It can cancel baseline voltages from 0.3 to 4.3
      V with an accuracy of 4.2 mV and can track and compensate for drifts up to 30
      mV/min. Performance was verified with MPN-coated CRs, where drift was measured
      and effectively cancelled. The circuit topology and size support an on-chip MPN
      coated CR sensor array. 

PMID- 23853266
TI  - Studies of MEMS Acoustic Sensors as Implantable Microphones for Totally
      Implantable Hearing-Aid Systems.
AB  - There is a need for high-quality implantable microphones for existing
      semiimplantable middle-ear hearing systems and cochlear prosthesis to make them
      totally implantable, thus overcoming discomfort, inconvenience, and social
      stigma. This paper summarizes and compares the results of an in-vitro study on
      three design approaches and the feasibility of using microelectromechanical
      system acoustic sensors as implantable microphones to convert the umbo vibration
      directly into a high-quality sound signal. The requirements of sensors were
      selected including the ability to withstand large body shocks or sudden changes
      of air pressure. Umbo vibration characteristics were extracted from literature
      and laboratory measurement data. A piezoelectric vibration source was built and
      calibrated to simulate the umbo vibration. Two laboratory models of the acoustic
      sensor were studied. The model-A device, using electrets-microphone as the
      sensor, was designed and tested in the laboratory and on temporal bones. The
      results verify that the laboratory measurement is consistent with the temporal
      bone characterization and achieves a near flat frequency response with a minimum
      detectable signal of a 65-dB sound-pressure-level (SPL) at 1 kHz. The model-B
      sensor was then designed to increase the sensitivity and provide an easy mounting
      on umbo. The model-B device can detect 40-dB SPL sound in the 1-2 kHz region,
      with 100-Hz channel bandwidth. The results of model-A and model-B displacement
      sensors and the acceleration sensor are summarized and compared. A preliminary
      design of the implantable displacement sensor for totally implantable hearing-aid
      systems is also presented. 

PMID- 23853267
TI  - A low-power high-speed ultra-wideband pulse radio transmission system.
AB  - We present a low-power high-speed ultra-wideband (UWB) transmitter with a
      wireless transmission test platform. The system is specifically designed for low
      power high-speed wireless implantable biosensors. The integrated transmitter
      consists of a compact pulse generator and a modulator. The circuit is fabricated
      in the 0.5-mum silicon-on-sapphire process and occupies 420 mum times 420 mum
      silicon area. The transmitter is capable of generating pulses with 1-ns width and
      the pulse rate can be controlled between 90 MHz and 270 MHz. We built a
      demonstration/testing system for the transmitter. The transmitter achieves a 14
      Mb/s data rate. With 50% duty cycle data, the power consumption of the chip is
      between 10 mW and 21 mW when the transmission distance is from 3.2 to 4 m. The
      core circuit size is 70 mum times 130 mum. 

PMID- 23853268
TI  - CMOS Ultrasound Transceiver Chip for High-Resolution Ultrasonic Imaging Systems.
AB  - The proposed CMOS ultrasound transceiver chip will enable the development of
      portable high resolution, high-frequency ultrasonic imaging systems. The
      transceiver chip is designed for close-coupled MEMS transducer arrays which
      operate with a 3.3-V power supply. In addition, a transmit digital beamforming
      system architecture is supported in this work. A prototype chip containing 16
      receive and transmit channels with preamplifiers, time-gain compensation
      amplifiers, a multiplexed analog-to-digital converter with 3 kB of on-chip SRAM,
      and 50-MHz resolution time delayed excitation pulse generators has been
      fabricated. By utilizing a shared A/D converter architecture, the number of A/D
      converter and SRAM is cut down to one, unlike typical digital beamforming systems
      which need 16 A/D converters for 16 receive channels. The chip was fabricated in
      a 0.35-mum standard CMOS process. The chip size is 10 mm(2), and its average
      power consumption in receive mode is approximately 270 mW with a 3.3-V power
      supply. The transceiver chip specifications and designs are described, as well as
      measured results of each transceiver component and initial pulse-echo
      experimental results are presented. 

PMID- 23853269
TI  - Sensitivity-Enhanced CMOS Phase Luminometry System Using Xerogel-Based Sensors.
AB  - We present the design and implementation of a phase luminometry sensor system
      with improved and tunable detection sensitivity achieved using a complementary
      metal-oxide semiconductor (CMOS) integrated circuit. We use sol-gel derived
      xerogel thin films as an immobilization media to house oxygen (O2) responsive
      luminescent molecules. The sensor operates on the principal of phase luminometry
      wherein a sinusoidal modulation signal is used to excite the luminophores
      encapsulated in the porous xerogel films and the corresponding phase shift of the
      emission signals is monitored. The phase shift is directly related to excited
      state lifetimes of the luminophores which in turn are related to the
      concentration of the target analyte species present in the vicinity of the
      luminophores. The CMOS IC, which consists of a 16 times 16 high-gain
      phototransistor array, current-to-voltage converter, amplifier and tunable phase
      shift detector, consumes an average power of 14 mW with 5-V power supply
      operating at a 38-kHz modulation frequency. The output of the IC is a dc voltage
      that corresponds to the detected luminescence phase shift with respect to the
      excitation signal. As a prototype, we demonstrate an oxygen sensor system by
      encapsulating the luminophore tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)
      within the xerogel matrices. The sensor system showed a fast response on the
      order of few seconds and we obtained a detection sensitivity of 118 mV per 1%
      change in O2 concentration. The system demonstrates a novel concept to tune and
      improve the detection sensitivity for specific concentrations of the target
      analyte in many biomedical monitoring applications. 

PMID- 23853270
TI  - A micropower electrocardiogram amplifier.
AB  - We introduce an electrocardiogram (EKG) preamplifier with a power consumption of
      2.8 muW, 8.1 muVrms input-referred noise, and a common-mode rejection ratio of 90
      dB. Compared to previously reported work, this amplifier represents a significant
      reduction in power with little compromise in signal quality. The improvement in
      performance may be attributed to many optimizations throughout the design
      including the use of subthreshold transistor operation to improve noise
      efficiency, gain-setting capacitors versus resistors, half-rail operation
      wherever possible, optimal power allocations among amplifier blocks, and the
      sizing of devices to improve matching and reduce noise. We envision that the
      micropower amplifier can be used as part of a wireless EKG monitoring system
      powered by rectified radio-frequency energy or other forms of energy harvesting
      like body vibration and body heat. 

PMID- 23853272
TI  - Code-division-multiplexed electrical impedance tomography spectroscopy.
AB  - Electrical impedance tomography uses multiple impedance measurements to image the
      internal conductivity of an object, such as the human body. Code-division
      multiplexing is proposed as a new method that can provide simultaneous impedance
      measurements of the multiple channels. Code division provides clear advantages of
      a wide frequency range at reduced cost and reduced complexity of sources. A
      potential drawback is the lack of perfectly orthogonal code sets. This caused an
      increase of 0.62% in root-mean-square spectral error when two codes were used to
      record two impedance channels simultaneously on a low-pass filter network. The
      method described provides images and spectra which are equivalent to the
      conventional time-multiplexed method, with increases in frequency resolution and
      measurement speed which may be of benefit in some applications of electrical
      impedance tomography spectroscopy. 

PMID- 23853271
TI  - Circuit and coil design for in-vitro magnetic neural stimulation systems.
AB  - Magnetic stimulation of neural tissue is an attractive technology because neural
      excitation may be affected without requiring implantation of electrodes. Pulsed
      discharge circuits are typically implemented for clinical magnetic stimulation
      systems. However, pulsed discharge systems can confound in-vitro experimentation.
      As an alternative to pulsed discharge circuits, we present a circuit to deliver
      asymmetric current pulses for generation of the magnetic field. We scaled the
      system down by using ferrite cores for the excitation coil. The scaled system
      allows observation using electrophysiological techniques and preparations not
      commonly used for investigation of magnetic stimulation. The design was refined
      using a comprehensive set of design equations. Circuit modeling and simulation
      demonstrate that the proposed system is effective for stimulating neural tissue
      with electric-field gradients generated by time-varying magnetic fields. System
      performance is verified through electrical test. 

PMID- 23853273
TI  - A Compact and Low-Cost MEMS Loudspeaker for Digital Hearing Aids.
AB  - A microelectromechanical-systems (MEMS)-based electromagnetically actuated
      loudspeaker to reduce form factor, cost, and power consumption, and increase
      energy efficiency in hearing-aid applications is presented. The MEMS loudspeaker
      has multilayer copper coils, an NiFe soft magnet on a thin polyimide diaphragm,
      and an NdFeB permanent magnet on the perimeter. The coil impedance is measured at
      1.5 Omega, and the resonant frequency of the diaphragm is located far from the
      audio frequency range. The device is driven by a power-scalable, 0.25-mum
      complementary metal-oxide semiconductor class-D SigmaDelta amplifier stage. The
      class-D amplifier is formed by a differential H-bridge driven by a single bit,
      pulse-density-modulated SigmaDelta bitstream at a 1.2-MHz clock rate. The
      fabricated MEMS loudspeaker generates more than 0.8-mum displacement, equivalent
      to 106-dB sound pressure level (SPL), with 0.13-mW power consumption. Driven by
      the SigmaDelta class-D amplifier, the MEMS loudspeaker achieves measured 65-dB
      total harmonic distortion (THD) with a measurement uncertainty of less than 10%.
      Energy-efficient and cost-effective advanced hearing aids would benefit from
      further miniaturization via MEMS technology. The results from this study appear
      very promising for developing a compact, mass-producible, low-power loudspeaker
      with sufficient sound generation for hearing-aid applications. 

PMID- 23853274
TI  - A PDMS-based integrated stretchable microelectrode array (isMEA) for neural and
      muscular surface interfacing.
AB  - Numerous applications in neuroscience research and neural prosthetics, such as
      electrocorticogram (ECoG) recording and retinal prosthesis, involve electrical
      interactions with soft excitable tissues using a surface recording and/or
      stimulation approach. These applications require an interface that is capable of
      setting up high-throughput communications between the electrical circuit and the
      excitable tissue and that can dynamically conform to the shape of the soft
      tissue. Being a compliant material with mechanical impedance close to that of
      soft tissues, polydimethylsiloxane (PDMS) offers excellent potential as a
      substrate material for such neural interfaces. This paper describes an integrated
      technology for fabrication of PDMS-based stretchable microelectrode arrays
      (MEAs). Specifically, as an integral part of the fabrication process, a
      stretchable MEA is directly fabricated with a rigid substrate, such as a thin
      printed circuit board (PCB), through an innovative bonding technology-via-bonding
      for integrated packaging. This integrated strategy overcomes the conventional
      challenge of high-density packaging for this type of stretchable electronics.
      Combined with a high-density interconnect technology developed previously, this
      stretchable MEA technology facilitates a high-resolution, high-density integrated
      system solution for neural and muscular surface interfacing. In this paper, this
      PDMS-based integrated stretchable MEA (isMEA) technology is demonstrated by an
      example design that packages a stretchable MEA with a small PCB. The resulting
      isMEA is assessed for its biocompatibility, surface conformability, electrode
      impedance spectrum, and capability to record muscle fiber activity when applied
      epimysially. 

PMID- 23853275
TI  - On the design of efficient multi-coil telemetry system for biomedical implants.
AB  - Two-coil based inductive coupling is a commonly used technique for wireless power
      and data transfer for biomedical implants. Because the source and load
      resistances are finite, two-coil systems generally achieve a relatively low power
      transfer efficiency. A novel multi-coil technique (using more than two coils) for
      wireless power and data transfer is considered to help overcoming this
      limitation. The proposed multi-coil system is formulated using both network
      theory and a two-port model. Using three or four coils for the wireless link
      allows for the source and load resistances to be decoupled from the Q-factor of
      the coils, resulting in a higher Q -factor and a corresponding improved power
      transfer efficiency (PTE). Moreover, due to the strong coupling between the
      driver and the transmitter coil (and/or between the receiver and the load coil),
      the multi-coil system achieves higher tunable frequency bandwidth as compared to
      its same sized two-coil equivalent. Because of the wider range of reflected
      impedance in the multi-coil system case, it is easier to tune the output power to
      the load and achieve the maximum power transfer condition for given source
      voltage than in a configuration with two coils. Experimental results showing a
      three-coil system achieving twice the efficiency and higher gain-bandwidth
      product compared to its two-coil counterpart are presented. In addition, a figure
      of merit for telemetry systems is defined to quantify the overall telemetry
      system performance. 

PMID- 23853276
TI  - Stacked phased array coils for increasing the signal-to-noise ratio in magnetic
      resonance imaging.
AB  - A new concept of using a stacked phased coil array to increase the signal-to
      circuit noise ratio (SCNR) in magnetic resonance imaging (MRI) is introduced.
      Unlike conventional phased coil arrays, the proposed stacked phased coil array is
      constructed by stacking the coil elements closely together in the vertical
      direction. Through a proper combination of the coil terminal voltages, the SCNR
      is shown to increase with the square root of the number of coil elements. A
      prototype two-element array is constructed and an experimental method is designed
      to determine the combiner coefficients in a simulated MRI electromagnetic field
      environment. The experimental results show that the mutual coupling effect among
      the array coils can be totally removed and the combiner output voltage increases
      with the number of coil elements. This demonstrates the feasibility of the
      proposed method. 

PMID- 23853277
TI  - An integrated open-cavity system for magnetic bead manipulation.
AB  - Superparamagnetic beads are increasingly used in biomedical assays to manipulate,
      transport, and maneuver biomaterials. We present a low-cost integrated system
      designed in bulk CMOS to manipulate and separate biomedical magnetic beads. The
      system consists of 8 * 8 coil-arrays suitable for single bead manipulation, or
      collaborative multi-bead manipulation, using pseudo-parallel executions. We
      demonstrate the flexibility of the design in terms of different coil sizes, DC
      current levels, and layout techniques. In one array module example, the size of a
      single coil is 30 MUm * 30 MUm and the full array occupies an area of 248 MUm *
      248 MUm in 0.5 MUm CMOS technology. The programmable DC current source supports 8
      discrete levels up to 1.5 mA. The total power consumption of the entire module is
      9 mW when running at full power. 

PMID- 23853278
TI  - A protein-based electrochemical biosensor array platform for integrated
      microsystems.
AB  - This paper elucidates challenges in integrating different classes of proteins
      into a microsystem and presents an electrochemical array strategy for
      heterogeneous protein-based biosensors. The overlapping requirements and
      limitations imposed by biointerface formation, electrochemical characterization,
      and microsystem fabrication are identified. A planar electrode array is presented
      that synergistically resolves these requirements using thin film Au and Ag/AgCl
      electrodes on a dielectric substrate. Using molecular self-assembly, electrodes
      were modified by nano-structures of two diverse proteins, alkali ion-channel
      protein and alcohol dehydrogenase enzyme. Electrochemical impedance spectroscopy
      and cyclic voltammetry measurements were performed to characterize sensor
      response to alkali ion and alcohol, respectively. This work demonstrates the
      viability of the electrochemical microsystem platform for heterogeneous protein
      based biosensor interfaces. 

PMID- 23853279
TI  - Noise analysis and performance comparison of low current measurement systems for
      biomedical applications.
AB  - In this paper, we report on the noise analysis of low current measurement systems
      for biomedical applications and their fundamental limits. We analyzed resistive
      feedback, capacitive feedback and current amplifier circuits for low current
      measurement systems. Detailed noise analysis for different biomedical
      applications are presented and matched with measurement data using a 0.5-MUm
      fabrication process. Based on the theoretical analysis and the corresponding
      measurement results, the capacitive feedback system provides better noise
      performance for the measurement of low current than the others. The capacitive
      feedback circuit is capable of measuring 750 fA RMS at a 10 kHz sampling rate,
      whereas the resistive feedback provides 4 pA and the current conveyor provides
      600 pA at the same bandwidth. This paper provides design guidelines to maximize
      the performance of low current measuring system for biomedical instrumentation
      and to provide the best performance available with CMOS technologies. 

PMID- 23853280
TI  - Biocompatible, high precision, wideband, improved Howland current source with
      lead-lag compensation.
AB  - The Howland current pump is a popular bioelectrical circuit, useful for
      delivering precise electrical currents. In applications requiring high precision
      delivery of alternating current to biological loads, the output impedance of the
      Howland is a critical figure of merit that limits the precision of the delivered
      current when the load changes. We explain the minimum operational amplifier
      requirements to meet a target precision over a wide bandwidth. We also discuss
      effective compensation strategies for achieving stability without sacrificing
      high frequency output impedance. A current source suitable for Electrical
      Impedance Tomography (EIT) was simulated using a SPICE model, and built to verify
      stable operation. This current source design had stable output impedance of 3.3
      MOmega up to 200 kHz, which provides 80 dB precision for our EIT application. We
      conclude by noting the difficulty in measuring the output impedance, and advise
      verifying the plausibility of measurements against theoretical limitations. 

PMID- 23853281
TI  - A learning-enabled neuron array IC based upon transistor channel models of
      biological phenomena.
AB  - We present a single-chip array of 100 biologically-based electronic neuron models
      interconnected to each other and the outside environment through 30,000 synapses.
      The chip was fabricated in a standard 350 nm CMOS IC process. Our approach used
      dense circuit models of synaptic behavior, including biological computation and
      learning, as well as transistor channel models. We use Address-Event
      Representation (AER) spike communication for inputs and outputs to this IC. We
      present the IC architecture and infrastructure, including IC chip, configuration
      tools, and testing platform. We present measurement of small network of neurons,
      measurement of STDP neuron dynamics, and measurement from a compiled spiking
      neuron WTA topology, all compiled into this IC. 

PMID- 23853282
TI  - Multicasting mesh AER: a scalable assembly approach for reconfigurable
      neuromorphic structured AER systems. Application to ConvNets.
AB  - This paper presents a modular, scalable approach to assembling hierarchically
      structured neuromorphic Address Event Representation (AER) systems. The method
      consists of arranging modules in a 2D mesh, each communicating bidirectionally
      with all four neighbors. Address events include a module label. Each module
      includes an AER router which decides how to route address events. Two routing
      approaches have been proposed, analyzed and tested, using either destination or
      source module labels. Our analyses reveal that depending on traffic conditions
      and network topologies either one or the other approach may result in better
      performance. Experimental results are given after testing the approach using high
      end Virtex-6 FPGAs. The approach is proposed for both single and multiple FPGAs,
      in which case a special bidirectional parallel-serial AER link with flow control
      is exploited, using the FPGA Rocket-I/O interfaces. Extensive test results are
      provided exploiting convolution modules of 64 * 64 pixels with kernels with sizes
      up to 11 * 11, which process real sensory data from a Dynamic Vision Sensor (DVS)
      retina. One single Virtex-6 FPGA can hold up to 64 of these convolution modules,
      which is equivalent to a neural network with 262 * 10(3) neurons and almost 32
      million synapses. 

PMID- 23853283
TI  - A micropower tilt-processing circuit.
AB  - This paper describes a novel analog circuit for extracting the tilt angle from
      the output of a linear microelectromechanical-system accelerometer. The circuit
      uses the accelerometer signal, together with the gravitational acceleration
      vector, to generate the tilt signal. Using a current-mode representation with
      metal-oxide semiconductor devices operating in weak inversion, the appropriate
      trigonometric function has been realized to compute tilt. Furthermore,
      implementing a long-time constant filter to extract the mean tilt level provides
      adaptation to the static tilt level. Specifically, this circuit has been designed
      as part of an implantable vestibular prosthesis to provide inclination signals
      for bypassing dysfunctional otolith end organs. The circuit has been fabricated
      in AustriaMicroSystems 0.35-mum 2P4M complementary metal-oxide semiconductor
      technology, and this paper presents the theory, implementation, and measured
      results. 

PMID- 23853284
TI  - Experimental Study of a TET System for Implantable Biomedical Devices.
AB  - Time-varying magnetic fields can be used to transfer power across the skin to
      drive implantable biomedical devices without the use of percutaneous wires.
      However, the main challenges of a transcutanoues energy transfer (TET) system are
      the temperature rise caused by power loss in the implanted circuitry and the
      changes in positioning between the external and internal coils due to fitting and
      changes in posture. This study presents a TET system with a closed-loop frequency
      based power regulation method to deliver the right amount of power to the load
      under variable coil coupling conditions. After implanting a TET system into adult
      sheep, the temperature rise in the internal and external coils of a TET system
      was measured for power delivery in the range of 5 W to 15 W. The sheep was housed
      in a temperature controlled (16 plusmn1degC, humidity 50plusmn10%) room, in
      accordance with the standard protocols implemented at the University of Auckland
      for sheep studies. A power-loss analysis for the overall system was performed.
      The system was capable of regulating power for axially aligned separations of up
      to 16 mm. The maximum power efficiency of the overall system was 82.1% and a
      maximum temperature rise of 2.7degC was observed on the implanted secondary coil.

PMID- 23853285
TI  - NeuralWISP: A Wirelessly Powered Neural Interface With 1-m Range.
AB  - We present the NeuralWISP, a wireless neural interface operating from far-field
      radio-frequency RF energy. The NeuralWISP is compatible with commercial RF
      identification readers and operates at a range up to 1 m. It includes a custom
      low-noise, low-power amplifier integrated circuit for processing the neural
      signal and an analog spike detection circuit for reducing digital computational
      requirements and communications bandwidth. Our system monitors the neural signal
      and periodically transmits the spike density in a user-programmable time window.
      The entire system draws an average 20 muA from the harvested 1.8-V supply. 

PMID- 23853286
TI  - Wireless micropower instrumentation for multimodal acquisition of electrical and
      chemical neural activity.
AB  - The intricate coupling between electrical and chemical activity in neural
      pathways of the central nervous system, and the implication of this coupling in
      neuropathologies, such as Parkinson's disease, motivates simultaneous monitoring
      of neurochemical and neuropotential signals. However, to date, neurochemical
      sensing has been lacking in integrated clinical instrumentation as well as in
      brain-computer interfaces (BCI). Here, we present an integrated system capable of
      continuous acquisition of data modalities in awake, behaving subjects. It
      features one channel each of a configurable neuropotential and a neurochemical
      acquisition system. The electrophysiological channel is comprised of a 40-dB
      gain, fully differential amplifier with tunable bandwidth from 140 Hz to 8.2 kHz.
      The amplifier offers input-referred noise below 2 muV rms for all bandwidth
      settings. The neurochemical module features a picoampere sensitivity potentiostat
      with a dynamic range spanning six decades from picoamperes to microamperes. Both
      systems have independent on-chip, configurable DeltaSigma analog-to-digital
      converters (ADCs) with programmable digital gain and resolution. The system was
      also interfaced to a wireless power harvesting and telemetry module capable of
      powering up the circuits, providing clocks for ADC operation, and telemetering
      out the data at up to 32 kb/s over 3.5 cm with a bit-error rate of less than 10(
      5). Characterization and experimental results from the electrophysiological and
      neurochemical modules as well as the full system are presented. 

PMID- 23853287
TI  - Conveying tactile feedback in sensorized hand neuroprostheses using a biofidelic
      model of mechanotransduction.
AB  - One approach to conveying tactile feedback from sensorized neural prostheses is
      to characterize the neural signals that would normally be produced in an intact
      limb and reproduce them through electrical stimulation of the residual peripheral
      nerves. Toward this end, we have developed a model that accurately replicates the
      neural activity evoked by any dynamic stimulus in the three types of
      mechanoreceptive afferents that innervate the glabrous skin of the hand. The
      model takes as input the position of the stimulus as a function of time, along
      with its first (velocity), second (acceleration), and third (jerk) derivatives.
      This input is filtered and passed through an integrate-and-fire mechanism to
      generate a train of spikes as output. The major conclusion of this study is that
      the timing of individual spikes evoked in mechanoreceptive fibers innervating the
      hand can be accurately predicted by this model. We discuss how this model can be
      integrated in a sensorized prosthesis and show that the activity in a population
      of simulated afferents conveys information about the location, timing, and
      magnitude of contact between the hand and an object. 

PMID- 23853288
TI  - A wireless integrated circuit for 100-channel charge-balanced neural stimulation.
AB  - The authors present the design of an integrated circuit for wireless neural
      stimulation, along with benchtop and in - vivo experimental results. The chip has
      the ability to drive 100 individual stimulation electrodes with constant-current
      pulses of varying amplitude, duration, interphasic delay, and repetition rate.
      The stimulation is performed by using a biphasic (cathodic and anodic) current
      source, injecting and retracting charge from the nervous system. Wireless
      communication and power are delivered over a 2.765-MHz inductive link. Only three
      off-chip components are needed to operate the stimulator: a 10-nF capacitor to
      aid in power-supply regulation, a small capacitor (< 100 pF) for tuning the coil
      to resonance, and a coil for power and command reception. The chip was fabricated
      in a commercially available 0.6- mum 2P3M BiCMOS process. The chip was able to
      activate motor fibers to produce muscle twitches via a Utah Slanted Electrode
      Array implanted in cat sciatic nerve, and to activate sensory fibers to recruit
      evoked potentials in somatosensory cortex. 

PMID- 23853289
TI  - A cantilever sensor with an integrated optical readout for detection of
      enzymatically produced homocysteine.
AB  - Microcantilever sensors have been recognized as a promising sensor platform for
      various chemical and biological applications. One of their major limitations is
      that the measurement of cantilever displacement typically involves elaborate off
      chip setups with free-space optics. An improved device, known as the optical
      cantilever, has been proposed recently to eliminate the external optics. The
      response of the optical cantilever is measured on-chip through integrated
      waveguides. However, this method has been previously demonstrated only for
      devices operating in air, whereas most chemical and biological samples are in
      solution state. We present the first optical cantilever capable of operation in
      liquid. We test it with the detection of homocysteine with a minimal
      concentration of 10 muM. The minimal measurable cantilever displacement and
      surface stress are 5 nm and 1 mN/m, respectively. The presented device will be
      used in studies of a homocysteine-producing bacterial pathway for the purpose of
      drug discovery. It can also be extended to various other chemical- or biological
      sensing applications by selecting an appropriate surface coating. 

PMID- 23853290
TI  - A low-power wide-range I-v converter for amperometric sensing applications.
AB  - This paper presents for the first time experimental results of a current-to
      voltage converter that can be used for amperometric sensing of currents ranging
      from 1 pA to 1 muA. The design strategy is optimized to achieve low power levels
      and, hence, make the circuit suitable for use in a wearable or implantable
      sensor. The power reduction is mostly achieved by combining transistors operating
      in the weak inversion region with floating-gate metal-oxide semiconductor devices
      and three different gain settings. The power consumption under normal operation
      is 9.82 muW. 

PMID- 23853291
TI  - Low-power circuits for the bidirectional wireless monitoring system of the
      orthopedic implants.
AB  - This paper proposes an architecture of the wireless monitoring system for the
      real-time monitoring of the orthopedic implants, which monitors the implant duty
      cycle, detects abnormal asymmetry, high amounts of force, and other conditions of
      the orthopedic implants. Data for diagnosis are communicated wirelessly by the
      radio-frequency (RF) signal between the embedded chip and the remote circuit. In
      different working modes, the system can be powered by the RF signal or stiff lead
      zirconate-titanate (PZT) ceramics which are able to convert mechanical energy
      inside the orthopedic implant into electrical energy. The power circuits with a
      variable ratio switched-capacitor (SC) dc-dc converter have been taped out with
      0.35-mum complementary metal-oxide semiconductor (CMOS) technology. The test
      results show that the SC converter can transfer the input voltage that ranges
      from 5 V to 14 V from the PZT ceramics into the voltage ranging from 2 V to 2.5 V
      which will be dealt with by a low drop-out circuit in the future work. The total
      efficiency of the SC converter is from 28% to 42% at full-time working mode. The
      analog-to-digital converter (ADC) circuits have been fabricated in a 0.18-mum
      1P6M CMOS process. The test results show that the ADC chip consumes only 12.5 muW
      in working mode and 150 nW in the sleep mode. The circuits, including RF
      circuits, ADC, and the microcontrol unit, have been implemented in a 0.18-mu m
      CMOS process. Future work includes some clinical experiments test in the
      application where PZT elements are used for power generation in total knee
      replacement implants. 

PMID- 23853292
TI  - A silicon cochlea with active coupling.
AB  - We present a mixed-signal very-large-scale-integrated chip that emulates
      nonlinear active cochlear signal processing. Modeling the cochlea's
      micromechanics, including outer hair cell (OHC) electromotility, this silicon
      (Si) cochlea features active coupling between neighboring basilar membrane (BM)
      segments-a first. Neighboring BM segments, each implemented as a class AB log
      domain second-order section, exchange currents representing OHC forces. This
      novel active-coupling architecture overcomes the major shortcomings of existing
      cascade and parallel filter-bank architectures, while achieving the highest
      number of digital outputs in an Si cochlea to date. An active-coupling
      architecture Si cochlea with 360 frequency channels and 2160 pulse-stream outputs
      occupies 10.9 mm(2) in a five-metal 1-poly 0.25-mum CMOS process. The chip's
      responses resemble that of a living cochlea's: Frequency responses become larger
      and more sharply tuned when active coupling is turned on. For instance, gain
      increases by 18 dB and Q 10 increases from 0.45 to 1.14. This enhancement
      decreases with increasing input intensity, realizing frequency-selective
      automatic gain control. Further work is required to improve performance by
      reducing large variations from tap to tap. 

PMID- 23853293
TI  - A CMOS power-efficient low-noise current-mode front-end amplifier for neural
      signal recording.
AB  - In this paper, a new current-mode front-end amplifier (CMFEA) for neural signal
      recording systems is proposed. In the proposed CMFEA, a current-mode preamplifier
      with an active feedback loop operated at very low frequency is designed as the
      first gain stage to bypass any dc offset current generated by the electrode
      tissue interface and to achieve a low high-pass cutoff frequency below 0.5 Hz. No
      reset signal or ultra-large pseudo resistor is required. The current-mode
      preamplifier has low dc operation current to enhance low-noise performance and
      decrease power consumption. A programmable current gain stage is adopted to
      provide adjustable gain for adaptive signal scaling. A following current-mode
      filter is designed to adjust the low-pass cutoff frequency for different neural
      signals. The proposed CMFEA is designed and fabricated in 0.18-MUm CMOS
      technology and the area of the core circuit is 0.076 mm(2). The measured high
      pass cutoff frequency is as low as 0.3 Hz and the low-pass cutoff frequency is
      adjustable from 1 kHz to 10 kHz. The measured maximum current gain is 55.9 dB.
      The measured input-referred current noise density is 153 fA /?Hz , and the power
      consumption is 13 MUW at 1-V power supply. The fabricated CMFEA has been
      successfully applied to the animal test for recording the seizure ECoG of Long
      Evan rats. 

PMID- 23853294
TI  - A 100-channel hermetically sealed implantable device for chronic wireless
      neurosensing applications.
AB  - A 100-channel fully implantable wireless broadband neural recording system was
      developed. It features 100 parallel broadband (0.1 Hz-7.8 kHz) neural recording
      channels, a medical grade 200 mAh Li-ion battery recharged inductively at 150 kHz
      , and data telemetry using 3.2 GHz to 3.8 GHz FSK modulated wireless link for 48
      Mbps Manchester encoded data. All active electronics are hermetically sealed in a
      titanium enclosure with a sapphire window for electromagnetic transparency. A
      custom, high-density configuration of 100 individual hermetic feedthrough pins
      enable connection to an intracortical neural recording microelectrode array. A
      100 MHz bandwidth custom receiver was built to remotely receive the FSK signal
      and achieved -77.7 dBm sensitivity with 10(-8) BER at 48 Mbps data rate. ESD
      testing on all the electronic inputs and outputs has proven that the implantable
      device satisfies the HBM Class-1B ESD Standard. In addition, the evaluation of
      the worst-case charge density delivered to the tissue from each I/O pin verifies
      the patient safety of the device in the event of failure. Finally, the
      functionality and reliability of the complete device has been tested on-bench and
      further validated chronically in ongoing freely moving swine and monkey animal
      trials for more than one year to date. 

PMID- 23853295
TI  - An energy-efficient, dynamic voltage scaling neural stimulator for a
      proprioceptive prosthesis.
AB  - This paper presents an 8 channel energy-efficient neural stimulator for
      generating charge-balanced asymmetric pulses. Power consumption is reduced by
      implementing a fully-integrated DC-DC converter that uses a reconfigurable
      switched capacitor topology to provide 4 output voltages for Dynamic Voltage
      Scaling (DVS). DC conversion efficiencies of up to 82% are achieved using
      integrated capacitances of under 1 nF and the DVS approach offers power savings
      of up to 50% compared to the front end of a typical current controlled neural
      stimulator. A novel charge balancing method is implemented which has a low level
      of accuracy on a single pulse and a much higher accuracy over a series of pulses.
      The method used is robust to process and component variation and does not require
      any initial or ongoing calibration. Measured results indicate that the charge
      imbalance is typically between 0.05%-0.15% of charge injected for a series of
      pulses. Ex-vivo experiments demonstrate the viability in using this circuit for
      neural activation. The circuit has been implemented in a commercially-available
      0.18 MUm HV CMOS technology and occupies a core die area of approximately 2.8
      mm(2) for an 8 channel implementation. 

PMID- 23853296
TI  - A blink restoration system with contralateral EMG triggered stimulation and real
      time artifact blanking.
AB  - Patients suffering from facial paralysis are on the hazard of disfigurement and
      loss of vision due to loss of blink function. Functional-electrical stimulation
      (FES) is one possible way of restoring blink and other functions in these
      patients. A blink restoration system for uni-lateral facial paralyzed patients is
      described in this paper. The system achieves restoration of synchronized blink
      through processing the myoelectric signal of orbicularis oculi at the normal side
      in real-time as the trigger to stimulate the paralyzed eyelid. Design issues are
      discussed, including EMG processing, stimulating strategies and real-time
      artifact blanking. Two artifact removal approaches based on sample and hold and
      digital filtering technique are proposed and implemented. Finally, the whole
      system has been verified on rabbit models. 

PMID- 23853297
TI  - A sub-microwatt asynchronous level-crossing ADC for biomedical applications.
AB  - A continuous-time level-crossing analog-to-digital converter (LC-ADC) for
      biomedical applications is presented. When compared to uniform-sampling (US) ADCs
      LC-ADCs generate fewer samples for various sparse biomedical signals. Lower power
      consumption and reduced design complexity with respect to conventional LC-ADCs
      are achieved due to: 1) replacing the n-bit digital-to-analog converter (DAC)
      with a 1-bit DAC; 2) splitting the level-crossing detections; and 3) fixing the
      comparison window. Designed and implemented in 0.18 MUm CMOS technology, the
      proposed ADC uses a chip area of 220 * 203 MUm(2). Operating from a supply
      voltage of 0.8 V, the ADC consumes 313-582 nW from 5 Hz to 5 kHz and achieves an
      ENOB up to 7.9 bits. 

PMID- 23853298
TI  - Automatic cell segmentation and nuclear-to-cytoplasmic ratio analysis for third
      harmonic generated microscopy medical images.
AB  - Traditional biopsy procedures require invasive tissue removal from a living
      subject, followed by time-consuming and complicated processes, so noninvasive in
      vivo virtual biopsy, which possesses the ability to obtain exhaustive tissue
      images without removing tissues, is highly desired. Some sets of in vivo virtual
      biopsy images provided by healthy volunteers were processed by the proposed cell
      segmentation approach, which is based on the watershed-based approach and the
      concept of convergence index filter for automatic cell segmentation. Experimental
      results suggest that the proposed algorithm not only reveals high accuracy for
      cell segmentation but also has dramatic potential for noninvasive analysis of
      cell nuclear-to-cytoplasmic ratio (NC ratio), which is important in identifying
      or detecting early symptoms of diseases with abnormal NC ratios, such as skin
      cancers during clinical diagnosis via medical imaging analysis. 

PMID- 23853299
TI  - Efficient data extraction method for near-infrared spectroscopy (NIRS) systems
      with high spatial and temporal resolution.
AB  - An hardware-efficient method for the extraction of hemodynamic responses in near
      infrared spectroscopy systems is proposed to increase the spatial and temporal
      resolution. The performance improvement is attributed to high signal-to-noise
      ratio receivers, a modulation scheme, and a multi-input-multi-output based data
      extraction algorithm. The proposed system shows more than twofold improvement in
      the figure of merit compared to conventional designs. Experimental results
      support the validity of the proposed system. 

PMID- 23853300
TI  - Low power and self-reconfigurable WBAN controller for continuous bio-signal
      monitoring system.
AB  - The WBAN controller with Branched Bus (BB) topology and Continuous Data
      Transmission (CDT) protocol with low power consumption and self-reconfigurability
      is proposed for wearable healthcare applications. The BB topology and CDT
      protocol is a combination of conventional Bus and Star topology and a variation
      from TDMA protocol, respectively, while they are able to compensate for the
      electrical fault in bio-signal monitoring system caused by the electrode
      deformation. Thanks to them, the proposed WBAN controller enables more reliable
      operation in continuous bio-signal monitoring applications such as sleep
      monitoring. 

PMID- 23853301
TI  - Wireless recording systems: from noninvasive EEG-NIRS to invasive EEG devices.
AB  - In this paper, we present the design and implementation of a wireless wearable
      electronic system dedicated to remote data recording for brain monitoring. The
      reported wireless recording system is used for a) simultaneous near-infrared
      spectrometry (NIRS) and scalp electro-encephalography (EEG) for noninvasive
      monitoring and b) intracerebral EEG (icEEG) for invasive monitoring. Bluetooth
      and dual radio links were introduced for these recordings. The Bluetooth-based
      device was embedded in a noninvasive multichannel EEG-NIRS system for easy
      portability and long-term monitoring. On the other hand, the 32-channel
      implantable recording device offers 24-bit resolution, tunable features, and a
      sampling frequency up to 2 kHz per channel. The analog front-end preamplifier
      presents low input-referred noise of 5 MU VRMS and a signal-to-noise ratio of 112
      dB. The communication link is implemented using a dual-band radio frequency
      transceiver offering a half-duplex 800 kb/s data rate, 16.5 mW power consumption
      and less than 10(-10) post-correction Bit-Error Rate (BER). The designed system
      can be accessed and controlled by a computer with a user-friendly graphical
      interface. The proposed wireless implantable recording device was tested in vitro
      using real icEEG signals from two patients with refractory epilepsy. The
      wirelessly recorded signals were compared to the original signals recorded using
      wired-connection, and measured normalized root-mean square deviation was under
      2%. 

PMID- 23853302
TI  - Implantable stimulator for epileptic seizure suppression with loading impedance
      adaptability.
AB  - The implantable stimulator for epileptic seizure suppression with loading
      impedance adaptability was proposed in this work. The stimulator consisted of the
      high voltage generator, output driver, adaptor, and switches, can constantly
      provide the required 40-MUA stimulus currents, as the loading impedance varied
      within 10 kOmega -300 kOmega. The performances of this design have been
      successfully verified in silicon chip fabricated by a 0.35- MUm 3.3-V/24-V CMOS
      process. The power consumption of this work was only 1.1 mW-1.4 mW. The animal
      test results with the fabricated chip of proposed design have successfully
      verified in the Long-Evans rats with epileptic seizures. 

PMID- 23853303
TI  - Nanofiber web textile dry electrodes for long-term biopotential recording.
AB  - Electrode properties are key to the quality of measured biopotential signals.
      Ubiquitous health care systems require long-term monitoring of biopotential
      signals from normal volunteers and patients in home or hospital environments. In
      these settings it is appropriate to use dry textile electrode networks for
      monitoring purposes, rather than the gel or saline-sponge skin interfaces used
      with Ag/AgCl electrodes. In this study, we report performance test results of two
      different electrospun conductive nanofiber webs, and three metal plated fabrics.
      We evaluated contact impedance, step response, noise and signal fidelity
      performance indices for all five dry electrodes, and compared them to those of
      conventional Ag/AgCl electrodes. Overall, we found nanofiber web electrodes
      matched Ag/AgCl electrode performance more closely than metal plated fabric
      electrodes, with the contact resistance and capacitance of Ag plated PVDF
      nanofiber web electrodes being most similar to Ag/AgCl over the 10 Hz to 500 kHz
      frequency range. We also observed that step responses of all three metal-plated
      fabrics were poorer than those for nanofiber web electrodes and Ag/AgCl. Further,
      noise standard deviation and noise power spectral densities were generally lower
      in nanofiber web electrodes than metal plated fabrics; and waveform fidelity of
      ECG-like traces recorded from nanofiber web electrodes was higher than for metal
      plated fabrics. We recommend textile nanofiber web electrodes in applications
      where flexibility, comfort and durability are required in addition to good
      electrical characteristics. 

PMID- 23853304
TI  - Ultra storage-efficient time digitizer for pseudorandom single photon counter
      implemented on a field-programmable gate array.
AB  - Pseudorandom single photon counting is a novel time-resolved optical measurement
      method, which is advantageous over convention techniques in terms of data
      acquisition speed and system cost. As a critical component of the pseudorandom
      single photon counter, the photon arriving time digitizer should be storage
      efficient for a high photon counting rate, while maintaining good time accuracy.
      We report an ultra storage-efficient time digitizer for a pseudorandom single
      photon counter in this paper, which is based on the asynchronous serial
      communication and can store the arriving time of every photon in 1-b memory
      space. In addition, a novel comb-wave modulator is proposed to achieve the dc
      balance required for asynchronous serial communication. Our prototype implemented
      on field-programmable gate arrays provides a time resolution of 400 ps. It can
      register up to 4.2-Giga photon arriving time tags with 1024 * 32-b memory space. 

PMID- 23853305
TI  - An Energy-Efficient ASIC for Wireless Body Sensor Networks in Medical
      Applications.
AB  - An energy-efficient application-specific integrated circuit (ASIC) featured with
      a work-on-demand protocol is designed for wireless body sensor networks (WBSNs)
      in medical applications. Dedicated for ultra-low-power wireless sensor nodes, the
      ASIC consists of a low-power microcontroller unit (MCU), a power-management unit
      (PMU), reconfigurable sensor interfaces, communication ports controlling a
      wireless transceiver, and an integrated passive radio-frequency (RF) receiver
      with energy harvesting ability. The MCU, together with the PMU, provides quite
      flexible communication and power-control modes for energy-efficient operations.
      The always-on passive RF receiver with an RF energy harvesting block offers the
      sensor nodes the capability of work-on-demand with zero standby power. Fabricated
      in standard 0.18-?m complementary metal-oxide semiconductor technology, the ASIC
      occupies a die area of 2 mm * 2.5 mm. A wireless body sensor network sensor-node
      prototype using this ASIC only consumes < 10-nA current under the passive standby
      mode, and < 10 ?A under the active standby mode, when supplied by a 3-V battery. 

PMID- 23853306
TI  - Digital Heart-Rate Variability Parameter Monitoring and Assessment ASIC.
AB  - This paper describes experimental results for an application-specific integrated
      circuit (ASIC), designed for digital heart rate variability (HRV) parameter
      monitoring and assessment. This ASIC chip measures beat-to-beat (RR) intervals
      and stores HRV parameters into its internal memory in real time. A wide range of
      short-term and long-term ECG signals obtained from Physionet was used for
      testing. The system detects R peaks with millisecond accuracy, and stores up to 2
      min of continuous RR interval data and up to 4 min of RR interval histogram. The
      prototype chip was fabricated in a 0.5 ?m complementary metal-oxide semiconductor
      technology on a 3*3 mm(2) die area, with a measured dynamic power consumption of
      10 ?W and measured leakage current of 2.62 nA. The HRV monitoring system
      including this HRV ASIC, an analog-to-digital converter, and a low complexity
      microcontroller was estimated to consume 32.5 ?V, which is seven times lower
      power than a stand-alone microcontroller performing the same functions. Compact
      size, low cost, and low power consumption make this chip suitable for a
      miniaturized portable HRV monitoring system. 

PMID- 23853307
TI  - An ultra-low-power pulse oximeter implemented with an energy-efficient
      transimpedance amplifier.
AB  - Pulse oximeters are ubiquitous in modern medicine to noninvasively measure the
      percentage of oxygenated hemoglobin in a patient's blood by comparing the
      transmission characteristics of red and infrared light-emitting diode light
      through the patient's finger with a photoreceptor. We present an analog single
      chip pulse oximeter with 4.8-mW total power dissipation, which is an order of
      magnitude below our measurements on commercial implementations. The majority of
      this power reduction is due to the use of a novel logarithmic transimpedance
      amplifier with inherent contrast sensitivity, distributed amplification,
      unilateralization, and automatic loop gain control. The transimpedance amplifier,
      together with a photodiode current source, form a high-performance photoreceptor
      with characteristics similar to those found in nature, which allows LED power to
      be reduced. Therefore, our oximeter is well suited for portable medical
      applications, such as continuous home-care monitoring for elderly or chronic
      patients, emergency patient transport, remote soldier monitoring, and wireless
      medical sensing. Furthermore, our design obviates the need for an A-to-D and
      digital signal processor and leads to a small single-chip solution. We outline
      how extensions of our work could lead to submilliwatt oximeters. 

PMID- 23853308
TI  - High-power integrated stimulator output stages with floating discharge over a
      wide voltage range for nerve stimulation.
AB  - Two integrated nerve stimulator circuits are described. Both generate passively
      charge-balanced biphasic stimulating pulses of 1 to 16 mA with 10-?s to 1-ms
      widths from 6- to 24-V supplies for implanted book electrodes. In both circuits,
      the electrodes are floating during the passive discharge anywhere within the
      range of the power rails, which may be up to 24 V. The first circuit is used for
      stimulation only. It uses a floating depletion transistor to enable continuous
      discharge of the electrodes, except when stimulating, without using power. The
      second circuit also allows neural signals to be recorded from the same tripole.
      It uses a modified floating complementary metal-oxide semiconductor (CMOS)
      discharge switch capable of operating over a range beyond the gate-to-source
      voltage limits of its transistors. It remains off for long periods using no power
      while recording. A 0.6-?m silicon-on-insulator CMOS technology has been used. The
      measured performance of the circuits has been verified using multiple tripoles in
      saline. 

PMID- 23853309
TI  - Design and implementation of therapeutic ultrasound generating circuit for dental
      tissue formation and tooth-root healing.
AB  - Biological tissue healing has recently attracted a great deal of research
      interest in various medical fields. Trauma to teeth, deep and root caries, and
      orthodontic treatment can all lead to various degrees of root resorption. In our
      previous study, we showed that low-intensity pulsed ultrasound (LIPUS) enhances
      the growth of lower incisor apices and accelerates their rate of eruption in
      rabbits by inducing dental tissue growth. We also performed clinical studies and
      demonstrated that LIPUS facilitates the healing of orthodontically induced teeth
      root resorption in humans. However, the available LIPUS devices are too large to
      be used comfortably inside the mouth. In this paper, the design and
      implementation of a low-power LIPUS generator is presented. The generator is the
      core of the final intraoral device for preventing tooth root loss and enhancing
      tooth root tissue healing. The generator consists of a power-supply subsystem, an
      ultrasonic transducer, an impedance-matching circuit, and an integrated circuit
      composed of a digital controller circuitry and the associated driver circuit.
      Most of our efforts focus on the design of the impedance-matching circuit and the
      integrated system-on-chip circuit. The chip was designed and fabricated using 0.8
      ?m high-voltage technology from Dalsa Semiconductor, Inc. The power supply
      subsystem and its impedance-matching network are implemented using discrete
      components. The LIPUS generator was tested and verified to function as designed
      and is capable of producing ultrasound power up to 100 mW in the vicinity of the
      transducer's resonance frequency at 1.5 MHz. The power efficiency of the
      circuitry, excluding the power supply subsystem, is estimated at 70%. The final
      products will be tailored to the exact size of teeth or biological tissue, which
      is needed to be used for stimulating dental tissue (dentine and cementum)
      healing. 

PMID- 23853310
TI  - Fabrication and Characterization of a Surface-Acoustic-Wave Biosensor in CMOS
      Technology for Cancer Biomarker Detection.
AB  - Design, fabrication, and characterization of a novel surface acoustic wave (SAW)
      biosensor in complementary metal-oxide semiconductor (CMOS) technology are
      introduced. The biosensor employs a streptavidin/biotin-based five-layer
      immunoassay for detecting a prominent breast cancer biomarker, mammoglobin
      (hMAM). There is a growing demand to develop a sensitive and specific assay to
      detect biomarkers in serum that could be used in the early detection of breast
      cancer, determining prognosis and monitoring therapy. CMOS-SAW devices present a
      viable alternative to the existing biosensor technologies by providing higher
      sensitivity levels and better performance at low costs. Two architectures
      (circular and rectangular) were developed and respective tests were presented for
      performance comparison. The sensitivities of the devices were analyzed primarily
      based on center frequency shifts. A frequency sensitivity of 8.704 pg/Hz and a
      mass sensitivity of 2810.25 m(2) /kg were obtained. Selectivity tests were
      carried out against bovine serum albumin. Experimental results indicate that it
      is possible to attach cancer biomarkers to functionalized CMOS-SAW sensor
      surfaces and selectively detect hMAM antigens with improved sensitivities,
      lowered costs, and increased repeatability of fabrication. 

PMID- 23853311
TI  - Characterization of deamidation at Asn138 in L-chain of recombinant humanized Fab
      expressed from Pichia pastoris.
AB  - A method was previously established for evaluating Asn deamidation by matrix
      assisted laser desorption/ionization time of flight-mass spectrometry using
      endoproteinase Asp-N. In this study, we demonstrated that this method could be
      applied to the identification of the deamidation site of the humanized fragment
      antigen-binding (Fab). First, a system for expressing humanized Fab from
      methylotrophic yeast Pichia pastoris was constructed, resulting in the
      preparation of ~30 mg of the purified humanized Fab from 1 l culture. Analysis of
      the L-chain derived from recombinant humanized Fab that was heated at pH 7 and
      100 degrees C for 1 h showed the deamidation at Asn138 in the constant region.
      Then, we prepared L-N138D Fab and L-N138A Fab and examined their properties. The
      circular dichroism (CD) spectrum of the L-N138D Fab was partially different from
      that of the wild-type Fab. The measurement of the thermostability showed that L
      N138D caused a significant decrease in the thermostability of Fab. On the other
      hand, the CD spectrum and thermostability of L-N138A Fab showed the same
      behaviour as the wild-type Fab. Thus, it was suggested that the introduction of a
      negative charge at position 138 in the L-chain by the deamidation significantly
      affected the stability of humanized Fab. 

PMID- 23853312
TI  - Association of epigenetic alterations in the human C7orf24 gene with the aberrant
      gene expression in malignant cells.
AB  - Human chromosome 7 open reading frame 24 (C7orf24)/gamma-glutamyl
      cyclotransferase has been suggested to be a potential diagnostic marker for
      several cancers, including carcinomas in the bladder urothelium, breast and
      endometrial epithelium. We here investigated the epigenetic regulation of the
      human C7orf24 promoter in normal diploid ARPE-19 and IMR-90 cells and in the MCF
      7 and HeLa cancer cell lines to understand the transcriptional basis for the
      malignant-associated high expression of C7orf24. Chromatin immunoprecipitation
      analysis revealed that histone modifications associated with active chromatin
      were enriched in the proximal region but not in the distal region of the C7orf24
      promoter in HeLa and MCF-7 cells. In contrast, elevated levels of histone
      modifications leading to transcriptional repression and accumulation of
      heterochromatin proteins in the C7orf24 promoter were observed in the ARPE-19 and
      IMR-90 cells, compared to the levels in HeLa and MCF-7 cancer cells. In parallel,
      the CpG island of the C7orf24 promoter was methylated to a greater extent in the
      normal cells than in the cancer cells. These results suggest that the
      transcriptional silencing of the C7orf24 gene in the non-malignant cells is
      elicited through heterochromatin formation in its promoter region; aberrant
      expression of C7orf24 associated with malignant alterations results from changes
      in chromatin dynamics. 

PMID- 23853313
TI  - Reference intervals for red cell variables and platelet counts in infants at 2, 5
      and 13 months of age: a cohort study.
AB  - AIMS: To derive reference values for red cell variables and platelet counts from
      a cohort of infants sampled at precise ages during the first 13 months of life.
      METHODS: Blood counts, reticulocyte counts and zinc protoporphyrin concentrations
      were obtained from healthy term infants of North European ancestry at 2, 5 and 13
      months of age. RESULTS: Mean cell volume (MCV) and mean cell haemoglobin (MCH)
      values did not differ significantly between 5 and 13 months and MCH concentration
      was unaffected by age. Values of all other variables at any one age differed
      significantly from those at the other two. Haemoglobin, mean cell haemoglobin,
      zinc protoporphyrin and platelet values (95% ranges) at 2 (n=119), 5 (n=97) and
      13 months (n=42) were, respectively, 91-125, 101-129 and 105-133 g/L; 28.6-33.1,
      24.5-28.7 and 24.3-28.7 pg; 36-116, 25-91 and 27-57 micromol/mol haem; and 216
      658, 241-591 and 209-455*10(9)/L. At 2 and 5 months, respectively, 26.9% and
      10.8% of subjects had platelet counts >500*10(9)/L. Reticulocyte counts at 2
      months and MCV and MCH values at 5 months were significantly higher in girls. In
      boys, red cell distribution width values were significantly higher at 5 months,
      and zinc protoporphyrin values at both 2 and 5 months. CONCLUSIONS: These
      findings indicate the value of obtaining reference data at precise ages during
      infancy and confirm and extend earlier reports indicating a gender difference in
      laboratory measures used to assess iron status in early infancy.

PMID- 23853314
TI  - Clinical significance of E-cadherin, beta-catenin, vimentin and S100A4 expression
      in completely resected squamous cell lung carcinoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic value of E
      cadherin, beta-catenin, vimentin and S100A4 expression in a cohort of squamous
      cell lung carcinoma (SqCC) patients. METHODS: Tumours from 204 patients with
      surgically resected SqCC were used for the immunohistochemical analyses of E
      cadherin, beta-catenin, vimentin and S100A4 expression. Correlations between the
      expression of these markers and clinicopathological parameters were analysed
      using the chi(2) test. The prognostic value of these markers was evaluated using
      univariate Kaplan-Meier survival analyses and multivariate Cox proportional
      hazards model analyses. RESULTS: Significant associations between E-cadherin
      expression and T stage (p=0.040), histological differentiation (p=0.005), lymph
      node metastasis (p<0.001), and recurrence (p<0.001) were identified. Decreased
      beta-catenin expression was significantly correlated with T stage (p=0.003) and
      lymph node metastasis (p=0.010). Vimentin expression was associated with
      histological differentiation (p=0.017) and lymph node metastasis (p=0.001).
      Moreover, significant correlations were observed between S100A4 expression and
      lymph node metastasis (p=0.020) and recurrence (p<0.001). In the univariate
      analyses, high E-cadherin expression was a positive indicator for overall
      survival (OS) (p<0.001) and disease-free survival (DFS) (p<0.001), whereas high
      S100A4 or vimentin expression were negative indicators for OS (p<0.001 and
      p=0.010, respectively) and DFS (p<0.001 and p=0.006, respectively). In the
      multivariate analyses, E-cadherin and S100A4 expression were independent
      prognostic factors for OS (HR 0.697, 95% CI 0.524 to 0.926, p=0.013, and HR
      1.508, 95% CI 1.122 to 2.027, p=0.007, respectively) and DFS (HR 0.634, 95% CI
      0.471 to 0.852, p=0.003, and HR 1.490, 95% CI 1.101 to 2.015, p=0.010,
      respectively). CONCLUSIONS: Effective analysis of E-cadherin and S100A4
      expression may allow for the identification of patients who are at a high risk of
      recurrence and poor prognosis in SqCC.

PMID- 23853315
TI  - Design and development of low-loss transformer for powering small implantable
      medical devices.
AB  - Small implantable medical devices, such as wireless capsule endoscopes, that can
      be swallowed have previously been developed. However, these devices cannot
      continuously operate for more than 8 h because of battery limitations; moreover,
      additional functionalities cannot be introduced. This paper proposes a design
      method for a high-efficiency energy transmission transformer (ETT) that can
      transmit energy transcutaneously to small implantable medical devices using
      electromagnetic induction. First, the authors propose an unconventional design
      method to develop such a high-efficiency ETT. This method can be readily used to
      calculate the exact transmission efficiency for changes in the material and
      design parameters (i.e., the magnetic material, transmission frequency, load
      resistance, etc.). Next, the ac-to-ac energy transmission efficiency is
      calculated and compared with experimental measurements. Then, suitable conditions
      for practical transmission are identified. A maximum efficiency of 33.1% can be
      obtained at a transmission frequency of 500 kHz and a receiving power of 100 mW
      for a receiving coil size of ?5 mm * 20 mm. Future design optimization is
      possible by using this method. 

PMID- 23853316
TI  - An 11 MU w, two-electrode transimpedance biosignal amplifier with active current
      feedback stabilization.
AB  - A novel two-electrode biosignal amplifier circuit is demonstrated by using a
      composite transimpedance amplifier input stage with active current feedback.
      Micropower, low gain-bandwidth product operational amplifiers can be used,
      leading to the lowest reported overall power consumption in the literature for a
      design implemented with off-the-shelf commercial integrated circuits (11 MUW).
      Active current feedback forces the common-mode input voltage to stay within the
      supply rails, reducing baseline drift and amplifier saturation problems that can
      be present in two-electrode systems. The bandwidth of the amplifier extends from
      0.05-200 Hz and the midband voltage gain (assuming an electrode-to-skin
      resistance of 100 kOmega) is 48 dB. The measured output noise level is 1.2 mV pp,
      corresponding to a voltage signal-to-noise ratio approaching 50 dB for a typical
      electrocardiogram (ECG) level input of 1 mVpp. Recordings were taken from a
      subject by using the proposed two-electrode circuit and, simultaneously, a three
      electrode standard ECG circuit. The residual of the normalized ensemble averages
      for both measurements was computed, and the power of this residual was 0.54% of
      the power of the standard ECG measurement output. While this paper primarily
      focuses on ECG applications, the circuit can also be used for amplifying other
      biosignals, such as the electroencephalogram. 

PMID- 23853317
TI  - Interpretations of Wrist/Grip Operations From SEMG Signals at Different Locations
      on Arm.
AB  - Surface electromyogram (SEMG) is a common method of measurement of muscle
      activity. It is noninvasive and is measured with minimal risk to the subject. The
      analysis of SEMG signal depends on a number of factors, such as amplitude as well
      as time- and frequency-domain properties. In the present investigation, the study
      of SEMG signals at different below elbow muscles for four operations of the hand
      wrist/grip-like opening (op)/closing (cl)/down (d)/up (u) was carried out.
      Myoelectric signals were extracted by using a single-channel SEMG amplifier
      consisting of a differential amplifier, noninverting amplifier, and interface
      module. Matlab softscope was used to acquire the SEMG signal from the hardware.
      After acquiring the data from six selected locations, interpretations were made
      for the estimation of parameters of the SEMG using the Matlab-filter algorithm
      and the fast Fourier transform technique. An interpretation of wrist/grip
      operations using principal component analysis (PCA) was carried out. PCA was used
      to identify the best SEMG signal capturing system out of two-channel, three
      channel, and four-channel systems. Two acupressure points (on wrist) were also
      selected for the analysis with other points on the arm. SEMG signal's study at
      different locations, including pressure points, will be a very helpful tool for
      the researchers in understanding the behavior of SEMG for the development of the
      prosthetic hand. 

PMID- 23853318
TI  - A Wireless Biomedical Signal Interface System-on-Chip for Body Sensor Networks.
AB  - Recent years have seen the rapid development of biosensor technology, system-on
      chip design, wireless technology. and ubiquitous computing. When assembled into
      an autonomous body sensor network (BSN), the technologies become powerful tools
      in well-being monitoring, medical diagnostics, and personal connectivity. In this
      paper, we describe the first demonstration of a fully customized mixed-signal
      silicon chip that has most of the attributes required for use in a wearable or
      implantable BSN. Our intellectual-property blocks include low-power analog sensor
      interface for temperature and pH, a data multiplexing and conversion module, a
      digital platform based around an 8-b microcontroller, data encoding for spread
      spectrum wireless transmission, and a RF section requiring very few off-chip
      components. The chip has been fully evaluated and tested by connection to
      external sensors, and it satisfied typical system requirements. 

PMID- 23853319
TI  - Design of a Tunable All-Digital UWB Pulse Generator CMOS Chip for Wireless
      Endoscope.
AB  - A novel tunable all-digital, ultrawideband pulse generator (PG) has been
      implemented in a standard 0.18-? m complementary metal-oxide semiconductor (CMOS)
      process for implantable medical applications. The chip shows that an ultra-low
      dynamic energy consumption of 27 pJ per pulse without static current flow at a
      200-MHz pulse repetition frequency (PRF) with a 1.8-V power supply and low area
      of 90 * 50 ?m(2). The PG generates tunable pulsewidth, amplitude, and transmit
      (Tx) power by using simple circuitry, through precise timing control of the H
      bridge output stage. The all-digital architecture allows easy integration into a
      standard CMOS process, thus making it the most suitable candidate for in-vivo
      biotelemetry applications. 

PMID- 23853320
TI  - Development of a Low-Cost FPGA-Based SSVEP BCI Multimedia Control System.
AB  - This paper proposes a low-cost field-programmable gate-array (FPGA)-based brain
      computer interface (BCI) multimedia control system, different from the BCI
      system, which uses bulky and expensive electroencephalography (EEG) measurement
      equipment, personal computer, and commercial real-time signal-processing
      software. The proposed system combines a customized stimulation panel, a
      brainwave-acquisition circuit, and an FPGA-based real-time signal processor and
      allows users to use their brainwave to communicate with or control multimedia
      devices by themselves. This study also designs a light-emitting diode stimulation
      panel instead of cathode ray tube or liquid-crystal display used in existing
      studies, to induce a stronger steady-state visual evoked potential (SSVEP), a
      kind of EEG, used as the input signal of the proposed BCI system. Implementing a
      prototype of the SSVEP-based BCI multimedia control system verifies the
      effectiveness of the proposed system. Experimental results show that the
      subjects' SSVEP can successfully control the multimedia device through the
      proposed BCI system with high identification accuracy. 

PMID- 23853321
TI  - A high frequency active voltage doubler in standard CMOS using offset-controlled
      comparators for inductive power transmission.
AB  - In this paper, we present a fully integrated active voltage doubler in CMOS
      technology using offset-controlled high speed comparators for extending the range
      of inductive power transmission to implantable microelectronic devices (IMD) and
      radio-frequency identification (RFID) tags. This active voltage doubler provides
      considerably higher power conversion efficiency (PCE) and lower dropout voltage
      compared to its passive counterpart and requires lower input voltage than active
      rectifiers, leading to reliable and efficient operation with weakly coupled
      inductive links. The offset-controlled functions in the comparators compensate
      for turn-on and turn-off delays to not only maximize the forward charging current
      to the load but also minimize the back current, optimizing PCE in the high
      frequency (HF) band. We fabricated the active voltage doubler in a 0.5-MUm 3M2P
      std . CMOS process, occupying 0.144 mm(2) of chip area. With 1.46 V peak AC input
      at 13.56 MHz, the active voltage doubler provides 2.4 V DC output across a 1
      kOmega load, achieving the highest PCE = 79% ever reported at this frequency. In
      addition, the built-in start-up circuit ensures a reliable operation at lower
      voltages. 

PMID- 23853322
TI  - In situ measurement of tissue impedance using an inductive coupling interface
      circuit.
AB  - In this work, a method of an inductive coupling impedance measurement (ICIM) is
      proposed for measuring the nerve impedance of a dorsal root ganglion (DRG) under
      PRF stimulation. ICIM provides a contactless interface for measuring the
      reflected impedance by an impedance analyzer with a low excitation voltage of 7
      mV. The paper develops a calibration procedure involving a 50-Omega reference
      resistor to calibrate the reflected resistance for measuring resistance of the
      nerve in the test. A de-embedding technique to build the equivalent transformer
      circuit model for the ICIM circuit is also presented. A batteryless PRF
      stimulator with ICIM circuit demonstrated good accuracy for the acute measurement
      of DRG impedance both in situ and in vivo. Besides, an in vivo animal experiment
      was conducted to show that the effectiveness of pulsed radiofrequency (PRF)
      stimulation in relieving pain gradually declined as the impedance of the
      stimulated nerve increased. The experiment also revealed that the excitation
      voltage for measuring impedance below 25 mV can prevent the excitation of a
      nonlinear response of DRG. 

PMID- 23853323
TI  - A touch probe method of operating an implantable RFID tag for orthopedic implant
      identification.
AB  - The major problem in operating an implantable radio-frequency identification
      (RFID) tag embedded on an orthopedic implant is low efficiency because of
      metallic interference. To improve the efficiency, this paper proposes a method of
      operating an implantable passive RFID tag using a touch probe at 13.56 MHz. This
      technology relies on the electric field interaction between two pairs of
      electrodes, one being a part of the touch probe placed on the surface of tissue
      and the other being a part of the tag installed under the tissue. Compared with
      using a conventional RFID antenna such as a loop antenna, this method has a
      better performance in the near field operation range to reduce interference with
      the orthopedic implant. Properly matching the touch probe and the tag to the
      tissue and the implant reduces signal attenuation and increases the overall
      system efficiency. The experiments have shown that this method has a great
      performance in the near field transcutaneous operation and can be used for
      orthopedic implant identification. 

PMID- 23853324
TI  - A dual-mode highly efficient class-E stimulator controlled by a low-Q class-E
      power amplifier through duty cycle.
AB  - This paper presents the design flow of two high-efficiency class-E amplifiers for
      the implantable electrical stimulation system. The implantable stimulator is a
      high-Q class-E driver that delivers a sine-wave pulsed radiofrequency (PRF)
      stimulation, which was verified to have a superior efficacy in pain relief to a
      square wave. The proposed duty-cycle-controlled class-E PRF driver designed with
      a high-Q factor has two operational modes that are able to achieve 100% DC-AC
      conversion, and involves only one switched series inductor and an unchanged
      parallel capacitor. The measured output amplitude under low-voltage (LV) mode
      using a 22% duty cycle was 0.98 V with 91% efficiency, and under high-voltage
      (HV) mode using a 47% duty cycle was 2.95 V with 92% efficiency. These modes were
      inductively controlled by a duty-cycle detector, which can detect the duty-cycle
      modulated signal generated from the external complementary low-Q class-E power
      amplifier (PA). The design methodology of the low-Q inductive interface for a non
      50% duty cycle is presented. The experimental results exhibits that the 1.5-V PA
      that consumes DC power of 14.21 mW was able to deliver a 2.9-V sine wave to a 500
      Omega load. The optimal 60% drain efficiency of the system from the PA to the
      load was obtained at a 10-mm coupling distance. 

PMID- 23853325
TI  - A low-power 13.56 MHz RF front-end circuit for implantable biomedical devices.
AB  - A low-power fully-integrated CMOS RF front-end circuit for a passive 13.56 MHz
      biomedical implant is presented. A 13.56 MHz binary phase shift keying (BPSK)
      signal is received by an internal coil. This front-end circuit is composed of a
      full-wave bridge rectifier, a linear regulator, a BPSK demodulator, and a
      clock/data recovery (CDR). A full-wave bridge rectifier converts the carrier
      waveform with the BPSK signal to an unregulated DC voltage. A linear regulator
      stabilizes the unregulated DC voltage to 1.8 V that serves as the DC source for
      the implant. A BPSK demodulator detects the incoming BPSK signal from the
      internal coil and translates the demodulated data to the CDR which can
      successfully recover the clock and data for the system controller. This chip with
      a core area of 0.45 mm(2) has been fabricated in a TSMC 0.18 MUm 1P6M CMOS
      technology. The total power consumed is only 632 MUW. 

PMID- 23853326
TI  - Flexible charge balanced stimulator with 5.6 fC accuracy for 140 nC injections.
AB  - Electrical stimulations of neuronal structures must ensure net injected charges
      to be zero for biological safety and voltage compliance reasons. We present a
      novel architecture of general purpose biphasic constant current stimulator that
      exhibits less than 5.6 fC error while injecting 140 nC charges using 1.4 mA
      currents. The floating current sources and conveyor switch based system can
      operate in monopolar or bipolar modes. Anodic-first or cathodic-first pulses with
      optional inter-phase delays have been demonstrated with zero quiescent current
      requirements at the analog front-end. The architecture eliminates blocking
      capacitors, electrode shorting and complex feedbacks. Bench-top and in-vivo
      measurement results have been presented with emulated electrode impedances
      (resistor-capacitor network), Ag-AgCl electrodes in saline and in-vivo (acute)
      peripheral nerve stimulations in anesthetized rats. 

PMID- 23853327
TI  - A small-area low-power current readout circuit using two-stage conversion method
      for 64-channel CNT sensor arrays.
AB  - In this paper, a small-area and low-power current readout circuit with a novel
      two-stage conversion method is presented for 64-channel CNT (carbon nanotube)
      sensor arrays. In the first stage, current of each CNT sensor is amplified by 64
      active input current mirrors (AICMs). In the second stage, the amplified current
      is converted to a voltage level through the shared variable gain amplifier (S
      VGA). Then the S-VGA output is digitalized by successive approximation register
      analog-to-digital converter (SAR-ADC). The proposed readout circuit significantly
      reduces chip area and power consumption, since VGA is shared over 64 channels and
      passive elements are used only in S-VGA. Fabricated chip area is 0.173 mm(2) in
      0.13 MUm CMOS technology. Measured power consumption and linearity error are
      73.06 MUW and 5.3%, respectively, at the input current range of 10 nA-10 MUA and
      conversion rate of 640 samples/s. A prototype real-time CNT sensor system was
      implemented using the fabricated readout circuit, and successfully detected
      alcohol reaction. 

PMID- 23853328
TI  - A patch-clamp ASIC for nanopore-based DNA analysis.
AB  - In this paper, a fully integrated high-sensitivity patch-clamp system is proposed
      for single-molecule deoxyribonucleic acid (DNA) analysis using a nanopore sensor.
      This system is composed of two main blocks for amplification and compensation.
      The amplification block is composed of three stages: 1) a headstage, 2) a voltage
      gain difference amplifier, and 3) a track-and-hold circuit, that amplify a minute
      ionic current variation sensed by the nanopore while the compensation block
      avoids the headstage saturation caused by the input parasitic capacitances during
      sensing. By employing design techniques novel for this application, such as an
      instrumentation--amplifier topology and a compensation switch, we minimize the
      deleterious effects of the input-offset voltage and the input parasitic
      capacitances while attaining hardware simplicity. This system is fabricated in a
      0.35 MUm 4M2P CMOS process and is demonstrated using an alpha-hemolysin protein
      nanopore for detection of individual molecules of single-stranded DNA that pass
      through the 1.5 nm-diameter pore. In future work, the refined system will
      functionalize single and multiple solid-state nanopores formed in integrated
      microfluidic devices for advanced DNA analysis, in scientific and diagnostic
      applications.

PMID- 23853329
TI  - A bionics chemical synapse.
AB  - Implementation of the current mode CMOS circuit for chemical synapses (AMPA and
      NMDA receptors) with dynamic change of glutamate as the neurotransmitter input is
      presented in this paper. Additionally, circuit realisation for receptor GABA(A)
      and GABA(B) with an electrical signal which symbolises gamma-Aminobutyric Acid
      (GABA) perturbation is introduced. The chemical sensor for glutamate sensing is
      the modified ISFET with enzyme (glutamate oxidase) immobilisation. The measured
      results from these biomimetics chemical synapse circuits closely match with the
      simulation result from the mathematical model. The total power consumption of the
      whole chip (four chemical synapse circuits and all auxiliary circuits) is 168.3
      MUW. The total chip area is 3 mm(2) in 0.35-MUm AMS CMOS technology.

PMID- 23853330
TI  - Active processing of spatio-temporal input patterns in silicon dendrites.
AB  - Capturing the functionality of active dendritic processing into abstract
      mathematical models will help us to understand the role of complex biophysical
      neurons in neuronal computation and to build future useful neuromorphic analog
      Very Large Scale Integrated (aVLSI) neuronal devices. Previous work based on an
      aVLSI multi-compartmental neuron model demonstrates that the compartmental
      response in the presence of either of two widely studied classes of active
      mechanisms, is a nonlinear sigmoidal function of the degree of either input
      temporal synchrony OR input clustering level. Using the same silicon model, this
      work expounds the interaction between both active mechanisms in a compartment
      receiving input patterns of varying temporal AND spatial clustering structure and
      demonstrates that this compartmental response can be captured by a combined
      sigmoid and radial-basis function over both input dimensions. This paper further
      shows that the response to input spatio-temporal patterns in a one-dimensional
      multi-compartmental dendrite, can be described by a radial-basis like function of
      the degree of temporal synchrony between the inter-compartmental inputs. 

PMID- 23853331
TI  - A field-programmable analog array development platform for vestibular prosthesis
      signal processing.
AB  - We report on a vestibular prosthesis signal processor realized using an
      experimental field programmable analog array (FPAA). Completing signal processing
      functions in the analog domain, the processor is designed to help replace a
      malfunctioning inner ear sensory organ, a semicircular canal. Relying on angular
      head motion detected by an inertial sensor, the signal processor maps angular
      velocity into meaningful control signals to drive a current stimulator. To
      demonstrate biphasic pulse control a 1 k Omega resistive load was placed across
      an H-bridge circuit. When connected to a 2.4 V supply, a biphasic current of 100
      MUA was maintained at stimulation frequencies from 50-350 Hz, pulsewidths from 25
      400 MU sec, and interphase gaps ranging from 25-250 MUsec. 

PMID- 23853332
TI  - A system verification platform for high-density epiretinal prostheses.
AB  - Retinal prostheses have restored light perception to people worldwide who have
      poor or no vision as a consequence of retinal degeneration. To advance the
      quality of visual stimulation for retinal implant recipients, a higher number of
      stimulation channels is expected in the next generation retinal prostheses, which
      poses a great challenge to system design and verification. This paper presents a
      system verification platform dedicated to the development of retinal prostheses.
      The system includes primary processing, dual-band power and data telemetry, a
      high-density stimulator array, and two methods for output verification. End-to
      end system validation and individual functional block characterization can be
      achieved with this platform through visual inspection and software analysis.
      Custom-built software running on the computers also provides a good way for
      testing new features before they are realized by the ICs. Real-time visual
      feedbacks through the video displays make it easy to monitor and debug the
      system. The characterization of the wireless telemetry and the demonstration of
      the visual display are reported in this paper using a 256-channel retinal
      prosthetic IC as an example. 

PMID- 23853333
TI  - CMOS neurotransmitter microarray: 96-channel integrated potentiostat with on-die
      microsensors.
AB  - A 8 * 12 array of integrated potentiostats for on-CMOS neurotransmitter imaging
      is presented. Each potentiostat channel measures bidirectional redox currents
      proportional to the concentration of a neurochemical. By combining the current-to
      frequency and the single-slope analog-to-digital converter (ADC) architectures a
      total linear dynamic range of 95 dB is achieved. A 3.8 mm * 3.1 mm prototype
      fabricated in a 0.35 MUm standard CMOS technology was integrated with flat and 3D
      on-die gold microelectrodes and an on-chip microfluidic network. It is
      experimentally validated in in-situ recording of neurotransmitter dopamine. 

PMID- 23853334
TI  - An amplitude-to-time conversion technique suitable for multichannel data
      acquisition and bioimpedance imaging.
AB  - In this paper we exploit the high timing resolution offered by microprocessors to
      develop an amplitude measurement approach that is convenient for high channel
      count portable sinusoidal recording systems such as the bioimpedance measurements
      used in impedance imaging. This approach reduces the number of components
      required per channel, reducing cost, size and power consumption compared to the
      traditional approaches. The setup uses two high performance comparators to
      convert amplitude difference to a timing difference. This is captured by a high
      speed microprocessor. A straightforward algorithm removes DC and timing offsets.
      We suggest three modes of operation: fast: less than one period of the input,
      normal: exactly one input period and high precision: multiple input periods. The
      mean signal-to-noise ratio was 40, 81, and 112.4 dB in fast, normal, and high
      precision mode respectively for a range of resistive loads. 

PMID- 23853335
TI  - An experimental setup to characterize MR switched gradient-induced potentials.
AB  - We have developed an experimental setup as an in vitro research tool for studying
      the contamination of electrophysiological signals (EPS) by MRI environment;
      particularly, when due to the switched gradient-induced potentials. The system is
      composed of: 1) a MRI compatible module for the transmission of the EPS into the
      MRI tunnel, 2) a gelatin-based tissue-mimicking phantom, placed inside the
      tunnel, in which EPS is injected, 3) a detection module composed of a five input
      channel MRI compatible transmitter placed inside the tunnel, allowing an on-site
      pre-amplification of the bio-potentials and their transmission, via an optical
      fiber cable, to a four filtered output per channel receiver (350 Hz, 160 Hz, 80
      Hz, and 40 Hz, for a total of 20 channels) placed in the control room, and 4) a
      signal processing algorithm used to analyze the generated induced potentials. A
      set of tests were performed to validate the electronic performances of the setup.
      We also present in this work an interesting application of the setup, i.e., the
      acquisition and analysis of the induced potentials with respect of the slice
      orientation for a given MRI sequence. Significant modifications of the time and
      frequency characteristics were observed with respect to axial, coronal or
      sagittal orientations. 

PMID- 23853336
TI  - A sub-mW fully-integrated pulse oximeter front-end.
AB  - This paper presents the implementation of the first fully integrated pulse
      oximeter front-end with a power consumption lower than 1 mW. This is enabled by
      system- and block-level noise optimisation, also detailed in the manuscript. The
      proposed design features an analogue feedback loop that enables fast and accurate
      regulation of the detected photocurrent level and a serial-to-parallel interface
      allowing for extensive programmability of several operation parameters. The front
      end was fabricated in the AMS 0.35 MUm technology and occupies an area of 1.35
      mm(2). Extensive measured results, both electrical and physiological from human
      subjects are reported, demonstrating an estimated SNR of 39 dB and ability to
      detect 2% changes in SpO2, similar to commercial pulse oximeters. This is despite
      the constrained power consumption which amounts to 0.31 mW for the LEDs and 0.53
      mW for the rest of the front-end from a 3.3 V supply. Statistical results from 20
      chips verify good matching across the Red and Infrared channels of the front-end
      and the accurate operation of the proposed analogue feedback loop.

PMID- 23853338
TI  - Analog VLSI Biophysical Neurons and Synapses With Programmable Membrane Channel
      Kinetics.
AB  - We present and characterize an analog VLSI network of 4 spiking neurons and 12
      conductance-based synapses, implementing a silicon model of biophysical membrane
      dynamics and detailed channel kinetics in 384 digitally programmable parameters.
      Each neuron in the analog VLSI chip (NeuroDyn) implements generalized Hodgkin
      Huxley neural dynamics in 3 channel variables, each with 16 parameters defining
      channel conductance, reversal potential, and voltage-dependence profile of the
      channel kinetics. Likewise, 12 synaptic channel variables implement a rate-based
      first-order kinetic model of neurotransmitter and receptor dynamics, accounting
      for NMDA and non-NMDA type chemical synapses. The biophysical origin of all 384
      parameters in 24 channel variables supports direct interpretation of the results
      of adapting/tuning the parameters in terms of neurobiology. We present
      experimental results from the chip characterizing single neuron dynamics, single
      synapse dynamics, and multi-neuron network dynamics showing phase-locking
      behavior as a function of synaptic coupling strength. Uniform temporal scaling of
      the dynamics of membrane and gating variables is demonstrated by tuning a single
      current parameter, yielding variable speed output exceeding real time. The 0.5
      CMOS chip measures 3 mm 3 mm, and consumes 1.29 mW. 

PMID- 23853337
TI  - A 1.2-V 165-MUW 0.29-mm2 multibit Sigma-Delta ADC for hearing aids using
      nonlinear DACs and with over 91 dB dynamic-range.
AB  - This paper describes the design and experimental evaluation of a multibit Sigma
      Delta (SigmaDelta) modulator (SigmaDeltaM) with enhanced dynamic range (DR)
      through the use of nonlinear digital-to-analog converters (DACs) in the feedback
      paths. This nonlinearity imposes a trade-off between DR and distortion, which is
      well suited to the intended hearing aid application. The modulator proposed here
      uses a fully-differential self-biased amplifier and a 4-bit quantizer based on
      fully dynamic comparators employing MOS parametric pre-amplification to improve
      both energy and area efficiencies. A test chip was fabricated in a 130 nm digital
      CMOS technology, which includes the proposed modulator with nonlinear DACs and a
      modulator with conventional linear DACs, for comparison purposes. The measured
      results show that the SigmaDeltaM using nonlinear DACs achieves an enhancement of
      the DR around 8.4 dB (to 91.4 dB). Power dissipation and silicon area are about
      the same for the two cases. The performance achieved is comparable to that of the
      best reported multibit SigmaDelta ADCs, with the advantage of occupying less
      silicon area (7.5 times lower area when compared with the most energy efficient
      SigmaDeltaM). 

PMID- 23853339
TI  - The 128-channel fully differential digital integrated neural recording and
      stimulation interface.
AB  - We present a fully differential 128-channel integrated neural interface. It
      consists of an array of 8 X 16 low-power low-noise signal-recording and
      generation circuits for electrical neural activity monitoring and stimulation,
      respectively. The recording channel has two stages of signal amplification and
      conditioning with and a fully differential 8-b column-parallel successive
      approximation (SAR) analog-to-digital converter (ADC). The total measured power
      consumption of each recording channel, including the SAR ADC, is 15.5 ?W. The
      measured input-referred noise is 6.08 ? Vrms over a 5-kHz bandwidth, resulting in
      a noise efficiency factor of 5.6. The stimulation channel performs monophasic or
      biphasic voltage-mode stimulation, with a maximum stimulation current of 5 mA and
      a quiescent power dissipation of 51.5 ?W. The design is implemented in 0.35-?m
      complementary metal-oxide semiconductor technology with the channel pitch of 200
      ?m for a total die size of 3.4 mm * 2.5 mm and a total power consumption of 9.33
      mW. The neural interface was validated in in vitro recording of a low-Mg(2+)/high
      K(+) epileptic seizure model in an intact hippocampus of a mouse. 

PMID- 23853340
TI  - An active approach for charge balancing in functional electrical stimulation.
AB  - Charge balancing is a major concern in functional electrical stimulation, since
      any excess charge accumulation over time leads to electrolysis with electrode
      dissolution and tissue destruction. This paper presents a new active approach for
      charge balancing using long-term offset regulation. Therefore, the electrode
      voltage is briefly monitored after each stimulation cycle and checked if it
      remains within a predefined voltage range. If not, an offset current is adjusted
      in order to track the biphasic current mismatch in upcoming stimulations. This
      technique is compared to a previously introduced active charge balancer as well
      as commonly used passive balancing techniques. Subsequently, the techniques are
      verified through experiments on a platinum black electrode in 0.9% saline
      solution. 

PMID- 23853341
TI  - Linear-phase delay filters for ultra-low-power signal processing in neural
      recording implants.
AB  - We present the design and implementation of linear-phase delay filters for ultra
      low-power signal processing in neural recording implants. We use these filters as
      low-distortion delay elements along with an automatic biopotential detector to
      perform integral waveform extraction and efficient power management. The
      presented delay elements are realized employing continuous-time OTA-C filters
      featuring 9th-order equiripple transfer functions with constant group delay. Such
      analog delay enables processing neural waveforms with reduced overhead compared
      to a digital delay since it does not requires sampling and digitization. It uses
      an allpass transfer function for achieving wider constant-delay bandwidth than
      all-pole does. Two filters realizations are compared for implementing the delay
      element: the Cascaded structure and the Inverse follow-the-leader feedback
      filter. Their respective strengths and drawbacks are assessed by modeling
      parasitics and non-idealities of OTAs, and by transistor-level simulations. A
      budget of 200 nA is used in both filters. Experimental measurements with the
      chosen filter topology are presented and discussed. 

PMID- 23853342
TI  - HermesD: A High-Rate Long-Range Wireless Transmission System for Simultaneous
      Multichannel Neural Recording Applications.
AB  - HermesD is a high-rate, low-power wireless transmission system to aid research in
      neural prosthetic systems for motor disabilities and basic motor neuroscience. It
      is the third generation of our "Hermes systems" aimed at recording and
      transmitting neural activity from brain-implanted electrode arrays. This system
      supports the simultaneous transmission of 32 channels of broadband data sampled
      at 30 ks/s, 12 b/sample, using frequency-shift keying modulation on a carrier
      frequency adjustable from 3.7 to 4.1 GHz, with a link range extending over 20 m.
      The channel rate is 24 Mb/s and the bit stream includes synchronization and error
      detection mechanisms. The power consumption, approximately 142 mW, is low enough
      to allow the system to operate continuously for 33 h, using two 3.6-V/1200-mAh Li
      SOCl2 batteries. The transmitter was designed using off-the-shelf components and
      is assembled in a stack of three 28 mm ? 28-mm boards that fit in a 38 mm ? 38 mm
      ? 51-mm aluminum enclosure, a significant size reduction over the initial version
      of HermesD. A 7-dBi circularly polarized patch antenna is used as the transmitter
      antenna, while on the receiver side, a 13-dBi circular horn antenna is employed.
      The advantages of using circularly polarized waves are analyzed and confirmed by
      indoor measurements. The receiver is a stand-alone device composed of several
      submodules and is interfaced to a computer for data acquisition and processing.
      It is based on the superheterodyne architecture and includes automatic frequency
      control that keeps it optimally tuned to the transmitter frequency. The HermesD
      communications performance is shown through bit-error rate measurements and eye
      diagram plots. The sensitivity of the receiver is -83 dBm for a bit-error
      probability of 10(-9). Experimental recordings from a rhesus monkey conducting
      multiple tasks show a signal quality comparable to commercial acquisition
      systems, both in the low-frequency (local field potentials) and upper-frequency
      bands (action potentials) of the neural signals. This system can be easily scaled
      up in terms of the number of channels and data rate to accommodate future
      generations of Hermes systems. 

PMID- 23853343
TI  - High-Speed OQPSK and Efficient Power Transfer Through Inductive Link for
      Biomedical Implants.
AB  - Biomedical implants require wireless power and bidirectional data transfer. We
      pursue our previous work on a novel topology for a multiple carrier inductive
      link by presenting the fabricated coils. We show that the coplanar geometry
      approach is better suited for displacement tolerance. We provide a theoretical
      analysis of the efficiency of power transfer and phase-shift-keying
      communications through an inductive link. An efficiency of up to 61% has been
      achieved experimentally for power transfer and a data rate of 4.16 Mb/s with a
      bit-error rate of less than 2 * 10(-6) has been obtained with our fabricated
      offset quadrature phase-shift keying modules due to the inductive link
      optimization presented in this paper. 

PMID- 23853344
TI  - [Editor's commentary].

PMID- 23853345
TI  - [Non-alcoholic fatty liver disease and steatohepatitis].
AB  - Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic
      manifestations of metabolic syndrome with close association with inzulin
      resistance and obesity, are the most common liver diseases, affecting up to a
      third of the population worldwide. They confer increased risk for hepatocellular
      carcinoma as well as cardiovascular diseases. The review aims to summarize
      advances in epidemiology, pathogenesis and clinical management of non-alcoholic
      fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and
      biomarkers, a novel non-invasive diagnostic tool the called "controlled
      attenuation parameter" measuring the attenuation of ultrasound generated by the
      transient elastography transducer, can quantitatively assess the hepatic fat
      content and differentiate between steatosis grades. At the same time, liver
      stiffness (fibrosis) can also be evaluated. The authors present their own results
      obtained with the latter procedure. In non-alcoholic fatty liver disease, the
      lifestyle intervention, weight loss, diet and exercise supported by cognitive
      behavioural therapy represent the basis of management. Components of metabolic
      syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be
      treated. Although there is no approved pharmacological therapy for NASH, it seems
      that long lasting administration of vitamin E in association with high dose
      ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated
      fatty acid substitution can also decrease liver fat, however, the optimal dose is
      not known yet. Further controlled clinical studies are warranted to establish the
      real value of any suggested treatment modalities for non-alcoholic fatty liver
      disease and non-alcoholic steatohepatitis, although these are in experimental
      phase yet.

PMID- 23853346
TI  - [Abnormal hepatic function tests in pregnancy: causes and consequences].
AB  - The well-known normal ranges of laboratory parameters are altered due to the
      broad spectrum of physiological changes as well as proinflammatory and
      procoagulant effects of pregnancy. Hepatic disorders of any aetiology can cause
      potential problems during gravidity. Most frequently toxic-effects, hepatotrop
      viruses (such as hepatitis B and C), metabolic syndrome and diseases with
      autoimmune background can be observed. When dealing with "pregnancy-specific
      hepatic syndromes", it is very important to consider the "timing-factors" of
      pathologic changes and deterioration of clinical pictures as well. Due to the
      progress in cholestasis management, early termination of pregnancy can be avoided
      in many cases. As the overlap is really broad between various hepatic disorders,
      a multidisciplinary cooperation of different sub-disciplines is emphasized in
      order to achieve proper diagnosis and curative measures at early phase.

PMID- 23853347
TI  - [Interdisciplinary aspects of and new drugs for chronic hepatitis B].
AB  - Hepatitis B virus infection is a significant health problem worldwide. The
      prevalence of HBsAg positivity is about 0.5-0.7% in Hungary. Liver cirrhosis
      and/or hepatocellular carcinoma develops in 15-40% of chronic hepatitis B virus
      infected patients without treatment. The ultimate goal of treatment would be to
      clear the virus from the infected subject; however, in practice, we can usually
      achieve long term suppression of viral replicaton with consequent prevention of
      the progression of liver disease, and reduction of the risk of the development of
      liver cirrhosis and hepatocellular carcinoma. Currently, there are two different
      treatment strategies for patients with chronic hepatitis B virus infection:
      therapy of finite duration with interferon or long-term treatment with
      nucleot(s)ide analogues. Entecavir and tenofovir are the two most effective
      nucleot(s)ide analogues with high barrier to resistance, thus, they can be
      confidently used as first-line treatments. Lamivudine engenders very high rates
      of resistance; adefovir is less efficacious than entecavir or tenofovir, and also
      engendering higher rates of resistance, thus none of them are recommended for
      initiation of a new treatment. Tenofovir is the treatment option in cases with
      lamivudine resistance, because entecavir has an unfavourable resistance-profile
      in this group of patients. Interferon is contraindicated during pregnancy. Should
      treatment of chronic hepatitis B virus infection be necessary during pregnancy,
      tenofovir, listed by the FDA as pregnancy category B drug, is to be preferred.
      Nucleot(s)ide analogues may be used to reduce the risk of intra-uterine and
      perinatal transmission of hepatitis B virus, which may occur in a proportion of
      newborns from highly viremic mothers, despite active and passive immunization.
      Similarly, tenofovir is recommended in the last trimester of pregnancy for women
      with high viremia. The risk of reactivation of chronic hepatitis B virus
      infection is high in HBsAg positive patients, and in patients with occult
      hepatitis B virus infection during and after chemotherapy or immunosuppressive
      treatment, including biological response modifiers (particularly related to
      rituximab therapy). Therefore, all candidates for these treatments should be
      screened for HBsAg and anti-HBc. Pre-emptive nucleot(s)ide analogues therapy
      should be initiated in patients with HBsAg positivity, and patients with occult
      hepatitis B virus infection. The role of general practitioners and occupational
      health physicians in the identification and the prevention of hepatitis B virus
      infection is stressed. Issues of high risk population groups, candidacy for
      vaccination, and methodology of active and passive immunisation are also reviewed
      in this paper.

PMID- 23853348
TI  - [Organizational characteristics of treatment for chronic hepatitis in Hungary:
      Hepatitis Registry and Priority Index].
AB  - Hepatitis Registry was developed by the Hepatology Section of the Hungarian
      Gastroenterology Society with the contribution of the Foundation for Liver
      Patients. The main task was to register all interferon based treatments of
      chronic hepatitis C and B and to facilitate the preauthorization process. The
      registry helped to clarify the number and characteristics of hepatitis C patients
      waiting for triple therapy; 3000 previously failed patients are still eligible
      for protease inhibitor therapy, 40% of them already developed cirrhosis stage and
      40% are null responders to the previous therapy. As a file is created for
      treatment authorization, the system counts automatically the Priority Index
      according to the calculation set in the guideline. Priority Index reflects the
      urgency of treatment. The most prominent parameter of the Index is the degree of
      fibrosis, but it also takes into account the progression rate, prognostic
      factors, and special situations.

PMID- 23853349
TI  - [Hemochromatosis: one form of iron-overload diseases].
AB  - Iron-overload diseases are typically insidious, causing progressive and
      irreversible organ injury before clinical symptoms develop. Some iron-overload
      diseases as HFE-associated hemochromatosis and beta-thalassemia are quite common,
      whereas others are very rare. Early diagnosis is important since iron toxicity
      can be attenuated or prevented. Significant progress of our knowledge on iron
      metabolism developed in the past years. We learned a lot about HFE gene
      mutations, function of ferroportin and hepcidin, the hypoferremia hormone
      produced by the liver. However, many questions are still open. Special forms of
      localized iron overload are the Hallervorden-Spatz syndrome and pantothenate
      kinase gene mutation associated neurodegeneration causing progressive
      extrapyramidal movement disorders. Neonatal hemochromatosis is a severe systemic
      iron-overload disorder due to gestational alloimmune liver disease caused by
      transplacental maternal IgG directed against the fetal liver. This review article
      gives an overview on iron metabolism and iron-overload disease. Pathomechanism,
      diagnosis and treatment of hereditary hemochromatosis are discussed.

PMID- 23853350
TI  - Supervised patient self-testing of warfarin therapy using an online system.
AB  - BACKGROUND: Point-of-care international normalized ratio (INR) monitoring devices
      simplify warfarin management by allowing selected patients to monitor their own
      therapy in their homes. Patient self-testing (PST) has been shown to improve the
      clinical outcomes of warfarin therapy compared to usual care. OBJECTIVE: To
      compare management of warfarin therapy using PST combined with online supervision
      by physicians via a custom system with usual warfarin management, which involved
      laboratory testing and physician dosing. METHODS: Interested patients were
      recruited via community pharmacies to participate in a warfarin PST training
      program. Participants were required to have a long-term indication for warfarin,
      have been taking warfarin for at least 6 months, and have Internet access in
      their home. The training involved two sessions covering theoretical aspects of
      warfarin therapy, use of the CoaguChek XS, and the study website. Following
      training, patients monitored their INR once weekly for up to 3 months. Patients
      and physicians utilized a secure website to communicate INR values, dosage
      recommendations, and clinical incidents. Physicians provided a 6-12 month history
      of INR results for comparison with study results. The percentage of time spent
      within the therapeutic INR range (TTR) was the primary outcome, with participants
      acting as their own historical controls. The percentage of INR tests in range and
      participant satisfaction were secondary outcomes. RESULTS: Sixteen patients
      completed training requirements. The mean age of participants was 69.8 (SD 10.1)
      years. TTR improved significantly from 66.4% to 78.4% during PST (P=.01), and the
      number of tests within the target range also improved significantly (from 66.0%
      at prior to the study to 75.9% during PST; P=.04). Patients and physicians
      expressed a high degree of satisfaction with the monitoring strategy and online
      system. CONCLUSIONS: PST supported by an online system for supervision was
      associated with improved INR control compared to usual care in a small group of
      elderly patients. Further research is warranted to investigate the clinical
      outcomes and cost-effectiveness of online systems to support patients monitoring
      medications and chronic conditions in the home.

PMID- 23853352
TI  - [Advances in genome-wide association study of tuberculosis].
AB  - Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is one of the oldest
      and most influential diseases in the history due to its devastating effect on
      health and high mortality rate worldwide. Tuberculosis causes more human deaths
      than any other single infectious disease and the incidence of the tuberculosis is
      increasing dramatically in recent years. Genome-wide association study (GWAS) has
      been used to delineate the genetic basis of tuberculosis, and several
      susceptibility genes and loci were found, which provids important clues to the
      early intervention and treatment of tuberculosis. However, due to difference in
      the population structure and host-pathogen interactions, GWAS on tuberculosis
      faces great challenges. In this review, we introduced the achievements of GWAS on
      tuberculosis, and illustrated challenges and strategies in the future study. 

PMID- 23853351
TI  - [The relationship between the polymorphism of immunity genes and both aging and
      age-related diseases].
AB  - Aging is acommon, progressive and irreversible state of multi-cell dysfunction.
      Immune aging mainly includes the declines of regenerative capacity and lymphoid
      lineage differentiation potential, the hyporesponsive to infection and
      vaccination, the hyperresponsive in the context of inflammatory pathology, and
      the increased risk of autoimmunity. The dysfunction of aged immune system
      accelerates the occurrence of aging and age-related diseases. The mutation of
      immunity genes that affect immune responses accelerates or slows aging process
      and age-related diseases. The frequencies of acquired immunity genes, such as
      immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased
      in the longevity populations. The increased susceptibility of immune inflammatory
      response, morbidity and mortality in the elderly is often associated with
      decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-beta1
      haplotype cnd10T/C, cnd25G/G, -988C/C, -800G/A, low proinflammatory fator TNFa
      level related extended TNF-A genotype -1031C/C, -863C/A, -857C/C, IL-6-174 CC and
      IFN-gamma+874 T allele as well. The innate immunity genes, such as highly
      expressed anti-inflammatory +896 G KIR4 allele, CCR5Delta32 variant, -765 C Cox-2
      allele, -1708 G and 21 C 5-Lox alleles are detected in centenarians. In age
      related diseases, a higher CMV-specific IgG antibody level in elderly individuals
      is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and
      an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the
      absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH
      402 His allele indicate high mortality in the elderly. In the present study, we
      review the advances in the polymorphism and haplotype of innate and adoptive
      immunity genes, and their association with both aging and age-related diseases.
      To strengthen the analysis of extended haplotypes, epigenetic studies of immunity
      genes and genetic study of hematopoietic stem cell senescence will be helpful to
      understand the accurate basis of aging-related immune genetics better. 

PMID- 23853353
TI  - [New insights in regulation factors of lipoprotein lipase].
AB  - Lipoprotein lipase (LPL) is an essential enzyme in the lipid metabolism, and
      proper regulation of LPL is important for controlling the delivery of lipid
      nutrients to tissues. Recent studies have identified glycosylphosphatidylinositol
      anchored high density lipoprotein-binding protein 1(GPIHBP1) as the important
      regulation factor of LPL that serves as a binding platform for lipolysis on the
      vascular lumen and an endothelial cell transporter transporting LPL from the
      interstitial spaces to the capillary lumen. In addition, several other regulation
      factors of LPL have also been identified including microRNAs, SorLA (Sortilin
      related receptor with A-type repeats), and apolipoproteins that are potentially
      important for regulating LPL activity. These discoveries provide new directions
      for understanding basic mechanisms of lipolysis and hyperlipidemia. In this
      update, we focused on summarizing recent progresses on GPIHBP1, the endothelial
      cell LPL transporter. We also highlighted the recent progresses on several other
      regulation factors of LPL that are relevant to the regulation of LPLactivity. 

PMID- 23853354
TI  - [Influence of environmental factors on DNA methylation].
AB  - DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) that
      transfer a methyl group from S-adenyl methionine (SAM) to the fifth carbon of a
      cytosine residue to form 5mC. DNA methylation affects the interaction between the
      histone and DNA, which changes the chromosome structure and has reverse
      relationship with gene expression in general. Up to now, more and more studies
      have confirmed that environmental factors can alter epigenetic modifications,
      which do not involve in changing DNA sequence. So it can explain the phenotype of
      creature in a certain degree. This article focused on the influence of
      environmental factors, such as temperature, nutrient supply, heavy metal, early
      stress and radiation, on DNA methylation change. As a matter of fact, it does not
      only change the DNA methylation in parents and offspring but also their behavior
      and phenotype. Overall, this review will help us get better understanding of the
      relationship between environmental factors and gene expression regulation. 

PMID- 23853355
TI  - [Understanding mitochondrial genome fragmentation in parasitic lice (Insecta:
      Phthiraptera)].
AB  - Lice are obligate ectoparasites of mammals and birds. Extensive fragmentation of
      mitochondrial genomes has been found in some louse species in the families
      Pediculidae, Pthiridae, Philopteridae and Trichodectidae. For example, the mt
      genomes of human body louse (Pediculus humanus), head louse (Pediculus capitis),
      and public louse (Pthirus pubis) have 20, 20 and 14 mini-chromosomes,
      respectively. These mini-chromosomes might be the results of deletion and
      recombination of mt genes. The factors and mechanisms of mitochondrial genome
      fragmentation are currently unknown. The fragmentation might be the results of
      evolutionary selection or random genetic drift or it is probably related to the
      lack of mtSSB (mitochondrial single-strand DNA binding protein). Understanding
      the fragmentation of mitochondrial genomes is of significance for understanding
      the origin and evolution of mitochondria. This paper reviews the recent advances
      in the studies of mito-chondrial genome fragmentation in lice, including the
      phenomena of mitochondrial genome fragmentation, characteristics of fragmented
      mitochondrial genomes, and some factors and mechanisms possibly leading to the
      mitochondrial genome fragmentation of lice. Perspectives for future studies on
      fragmented mt genomes are also discussed. 

PMID- 23853356
TI  - [Progress and application of zebrafish in regenerative medicine].
AB  - The phenomenon of "tissue regeneration" has attracted numerous biologists for
      many years. Regenerative capacity differs greatly across species. The lower
      vertebrates such as zebrafish have exceptionally high regeneration abilities,
      while most high vertebrate species including humans do not have a remarkable
      ability for regeneration. It has been found zebrafish has a strong ability to
      regenerate a variety of tissues and organs including fins, heart, retina, optic
      nerve, spinal cord, liver, and sensory hair cells. Thus, we can learn useful
      information from the zebrafish regeneration model to understand the human
      regeneration defects and promote the development of regenerative medicine. This
      review summarizes the current research status for regeneration of heart, nerve,
      liver, and fin regeneration in zebrafish. 

PMID- 23853357
TI  - [Progress on identification and analysis of DNase I hypersensitive sites in plant
      genomes].
AB  - Eukaryotes's gene expression and regulation relies on the interaction of their
      cis-acting elements and trans-acting factors. The cis-elements are specific DNA
      sequences in the genome and frequently located in the untranslated regions. The
      trans-acting factors are usually considered to be proteins that bind to the cis
      acting sequences to regulate gene expression. It is well known that the cis
      elements are always associated with DNase I hypersensitive site, which is a
      signature of open chromatin. The identification of all the functional cis-element
      using high-throughput method in plant genome has not been initiated in plant
      genomes. With the rapid achievement of genomics studies, an increasing number of
      plant genomes have been sequenced. Genome-wide identification of DNase I
      hypersensitive sites will be a considerably efficient method to locate cis
      element in plants, which will provide a vital potential for further plant
      functional genomics. The present review is to reveal the recent progresses on
      identification and analysis of DNase I hypersensitive site in plant genomes. 

PMID- 23853358
TI  - [Calcium sensors and their stress signaling pathways in plants].
AB  - Calcium (Ca2+) signals are a core regulator of plant growth and development and
      responses to environmental cues and thus highlighted in plant physiological and
      stress biology. External stimuli trigger specifically intracellular spatial and
      temporal [Ca2+]cyt variations in plant cells. This [Ca2+]cyt variations will be
      sensed and decoded by calcium sensors and, in turn, calcium sensor interacting
      proteins transmit resulting signals to the downstream effectors to activate the
      expression of early response genes or promote ion channel activities, finally
      leading to specific stress responses. How the plant cell distinguishes different
      types or intensity of external stimuli through sensing intracellular spatial and
      temporal variations of Ca2+ signals is a scientific issue recently highlighted by
      plant biologists. This review summarized recent advances in the research field of
      plant calcium sensors, including the structural characteristics, functional
      roles, and stress signaling path-ways of calcium-dependent protein kinases
      (CDPKs), calmodulins (CaMs), calmodulin-like proteins (CMLs), and cal-cineurin B
      like proteins (CBLs) and their interacting kinases (CIPKs), and moreover provided
      new insights and perspectives. 

PMID- 23853359
TI  - [Cytogenetic analysis of 105 new human abnormal karyotypes].
AB  - To analyze the genetic effect of the abnormal chromosome karyotype, we summarized
      and studied the clinical data of the new abnormal karyotypes diagnosed at the
      Guangxi Zhuang Autonomous Region Women and Children Care Hospital from January
      2009 to July 2012. The samples were cultured routinely for the karyotype analysis
      using G banding and C banding. Chromosomal aberrations were named according to
      the International System for Human Cytogenetic Nomenclature (ISCN 2009). Among
      tested samples, 105 new human abnormal karyotypes were identified (86 reciprocal
      translocation, 10 chromosomal inversion, six derivative chromosome, one
      duplication, one isochromosome, one partial trisomy and monosomy). The results
      suggest that chromosomal abnormalities were a major cause of miscarriage,
      infertility, congenital abnormalities, mental retardation and amenorrhea in
      humans. 

PMID- 23853360
TI  - [cDNA cloning and expression analysis of Opn4 gene in retina of swines].
AB  - The purpose of this work was to elucidate the characteristics and the expression
      profiles of porcine Opn4 during developmental stages and different times of the
      day. The coding sequence of Opn4 gene was cloned. The mRNA expression levels of
      Opn4 gene in the retina of the swines during developmental stages and different
      times of the day were examined. The results showed that the swine ORF of Opn4
      gene was 1 437 bp in length which encodes 478 amino acids residues with the
      molecular formula of C2398H3705N623O651S23. The expression level of Opn4 in the
      day was significantly higher than that in the night (P<0.01). During the growing
      periods, Opn4 started expressing as early as 34 d in the embryonic phase with the
      lowest level (P<0.01), reached to a peak 1 day after birth (P<0.01), and then
      stayed at a moderate standard. The difference of Opn4 expressions among the
      swines at 1th month, 4th month, and 84th month was not significantly different
      (P>0.05). In total, results showed that the Opn4 gene can regulate the biological
      rhythm of the swines. Furthermore, it play an important role in mediate the
      responsibility to the light in the postnatal swines. 

PMID- 23853361
TI  - [Cloning and promoter analysis of gonadotrophin-releasing hormone II in the
      orange-spotted grouper (Epinephelus coioides)].
AB  - Gonadotrophin-releasing hormone (GnRH) is a key regulator of reproduction in all
      vertebrates. We first cloned the cDNA and genomic DNA sequences coding for GnRHII
      gene in the orange-spotted grouper (Epinephelis coioides), an economically
      important marine fish, and then cloned its promoter sequence. The region
      responsible for the cell-specific expression of GnRHII was located between -2005
      bp to -956 bp from the translation start site. GnRHII promoter driven EGFP
      expression in transgenic zebrafish showed that GnRHII-positive neurons were
      primarily located in the midbrain and in the eyes. Our results provide an
      improved understanding of the regulatory mechanism and function of GnRHII of E.
      coioides. 

PMID- 23853362
TI  - [Combining ability analysis for SP4 lines of maize from space flight].
AB  - Three maize (Zea mays L.) inbred lines 08-641, RP125, and 18-599 were carried
      into cosmic space by recoverable satellite "Shijian 8". Some mutant lines were
      selected from SP4 and combinations were made according to the NC II genetic
      design. The materials were planted in Sichuan and Yunnan separately to analyze
      combining ability based on the incomplete diallel cross design. The results
      showed that space flight affected the combining ability of mutant lines, and the
      GCA value of mutant lines were different in two kinds of environmental condition.
      The GCA of ear length, row per ear, kernel per row, and yield per plant for the
      mutant line C03 showed substantial increase compared with the control 08-641; the
      GCA of row per ear, kernel per row, and other yield component traits for the
      mutant lines C01 and C04 were significantly higher than those of the control. The
      SCA of yield and yield components for the combinations derived from the mutant
      lines C06, R18, and S22 were higher than others. These results laid a material
      foundation for maize breeding and provided some important references for
      improving and utilizing the mutant lines. 

PMID- 23853363
TI  - [Functions of ANAC092 involved in regulation of anther development in Arabidopsis
      thaliana].
AB  - NAC family is a class of transcription factors that have been typically found in
      plant with various functions. This type of genes plays a key regulatory role in
      secondary plant growth, cell division, senescence, especially in the hormone and
      signaling pathways. ANAC092 was reported to function in relation to lateral root
      development and senescence. The promoter and in situ hybridization analyses
      showed that ANAC092 was expressed temporally in the process of anther
      development. The gene was expressed in tapetum at stages 8-11 of anther
      development and reached the highest amount at stages 9-10, which was overlapped
      with the expression period of AMS (Aborted microspores). In this study, we
      constructed ANAC092 over-expression system, and identified homozygous transgenic
      lines. Compared with the wild type, the number of pollen grains in the transgenic
      line was decreased significantly, but the length of pollen grain was increased.
      qRT-PCR analysis showed that the expression of genes related to pollen
      development, e.g., SPL, EMS1, DYT1, and AMS was in-creased in the over-expression
      plants. Bioinformatics results showed that ANAC092 promoter sequence possessed
      seven AMS binding sites. All the results showed that ANAC092 is possibly located
      in the downstream of AMS and plays an im-portant role in the process of pollen
      development. 

PMID- 23853364
TI  - [Duplex genotyping of CYP2C19*2 and CYP2C19*3 by high-resolution melting curve
      analysis].
AB  - Clopidogrel is a widely used anti-platelet agent for the prevention of arterial
      thrombosis. It has been suggested that clopidogrel may be less effective in
      inhibiting platelet aggregation among patients who are carriers of CYP2C19*2 and
      CYP2C19*3, two loss-of-function CYP2C19 alleles, which are associated with
      reduced conversion of clopidogrel to its active metabolite. The objective of this
      research was to develop a simple and accurate method for genotyping of CYP2C19*2
      and CYP2C19*3 simultaneously in one closed-tube using high-resolution melting
      curve (HRM) analysis. Two amplicons bracketing CYP2C19*2 and CYP2C19*3 gene
      variants were designed, and AT- or GC-rich 5' tails were added to selected
      primers to ensure two different amplicons with non-overlapping melting curves.
      Sixty-four random DNA samples were all fast and sensitively genotyped by HRM
      analysis. This method was validated by DNA sequencingtechnique, and genotypes
      obtained using the HRM approach perfectly matched the genotypes obtained by DNA
      sequencing technique. Therefore, this HRM-based assay allows simple and accurate
      duplex genotyping of CYP2C19*2 and CYP2C19*3 simultaneously in one closed-tube.
      This method is expected to be applied in clinical laboratory to guide indi-vidual
      dosage design of clopidogrel. 

PMID- 23853365
TI  - [Research progress on the cloning of Mendel's gene in pea (Pisum sativum L.) and
      its application in genetics teaching].
AB  - One hundred and fifty years ago, Gregor Mendel investigated the segregation of
      seven traits in pea (Pisum sativum) and established the law of segregation and
      the law of independent assortment in genetics. After the two laws of genetics
      were rediscovered in 1900, the seven traits have been extensively investigated in
      the fields of plant physiology and biochemistry as well as in the cell and
      molecular levels. Recently, with the development of molecular technology in
      genetics, four genes for seed shape (R), stem length (Le), cotyledon colour (I),
      and flower colour (A) have been cloned and sequenced; and another three genes for
      immature pod colour (Gp), fasciation (Fa) and pod form (V) have been located in
      the linkage groups, respectively. The identification and cloning of the four
      Mendel's genes will help deeply understand the basic concept of gene in many
      respects: like the diversity of gene function, the different origins for gene
      mutation in molecular level, and the molecular nature of a dominant gene or a
      recessive gene. In teaching of genetics, the introduction of most recent research
      advancements of cloning of Mendel's genes to the students and the interpretation
      of the Mendel's laws in molecular level will help students promote their learning
      interests in genetics and help students grasp the whole content from classical
      genetics to molecular genetics and the developmental direction of this subject. 

PMID- 23853366
TI  - Low-power low-voltage current readout circuit for inductively powered implant
      system.
AB  - Low voltage and low power are two key requirements for on-chip realization of
      wireless power and data telemetry for applications in biomedical sensor
      instrumentation. Batteryless operation and wireless telemetry facilitate robust,
      reliable, and longer lifetime of the implant unit. As an ongoing research work,
      this paper demonstrates a low-power low-voltage sensor readout circuit which
      could be easily powered up with an inductive link. This paper presents two
      versions of readout circuits that have been designed and fabricated in bulk
      complementary metal-oxide semiconductor (CMOS) processes. Either version can
      detect a sensor current in the range of 0.2 MUA to 2 MUA and generate square-wave
      data signal whose frequency is proportional to the sensor current. The first
      version of the circuit is fabricated in a 0.35-MU m CMOS process and it can
      generate an amplitude-shift-keying (ASK) signal while consuming 400 MU W of power
      with a 1.5-V power supply. Measurement results indicate that the ASK chip
      generates 76 Hz to 500 Hz frequency of a square-wave data signal for the
      specified sensor current range. The second version of the readout circuit is
      fabricated in a 0.5-MU m CMOS process and produces a frequency-shift-keying (FSK)
      signal while consuming 1.675 mW of power with a 2.5-V power supply. The generated
      data frequency from the FSK chip is 1 kHz and 9 kHz for the lowest and the
      highest sensor currents, respectively. Measurement results confirm the
      functionalities of both prototype schemes. The prototype circuit has potential
      applications in the monitoring of blood glucose level, lactate in the
      bloodstream, and pH or oxygen in a physiological system/environment. 

PMID- 23853367
TI  - A real-time wireless brain-computer interface system for drowsiness detection.
AB  - A real-time wireless electroencephalogram (EEG)-based brain-computer interface
      (BCI) system for drowsiness detection has been proposed. Drowsy driving has been
      implicated as a causal factor in many accidents. Therefore, real-time drowsiness
      monitoring can prevent traffic accidents effectively. However, current BCI
      systems are usually large and have to transmit an EEG signal to a back-end
      personal computer to process the EEG signal. In this study, a novel BCI system
      was developed to monitor the human cognitive state and provide biofeedback to the
      driver when drowsy state occurs. The proposed system consists of a wireless
      physiological signal-acquisition module and an embedded signal-processing module.
      Here, the physiological signal-acquisition module and embedded signal-processing
      module were designed for long-term EEG monitoring and real-time drowsiness
      detection, respectively. The advantages of low owner consumption and small volume
      of the proposed system are suitable for car applications. Moreover, a real-time
      drowsiness detection algorithm was also developed and implemented in this system.
      The experiment results demonstrated the feasibility of our proposed BCI system in
      a practical driving application. 

PMID- 23853368
TI  - Magnetic tracking system for radiation therapy.
AB  - Intensity-modulated radiation therapy (IMRT) requires precise delivery of the
      prescribed dose of radiation to the target and surrounding tissue. Irradiation of
      moving body anatomy is possible only if stable, accurate, and reliable
      information about the moving body structures are provided in real time. This
      paper presents a magnetic position tracking system for radiation therapy. The
      proposed system uses only four transmitting coils and an implantable transponder.
      The four transmitting coils generate a magnetic field which is sensed and
      measured by a biaxial magnetoresistive sensor in the transponder in the tumor.
      The transponder transmits the information back to a computer to determine the
      position of the transponder allowing it to track the tumor in real time. The
      transmission of the information from the transponder to the computer can be wired
      or wireless. Measurements using a biaxial sensor agree well with the field
      strength calculated from the ideal equations. The translation from the
      measurement data to the 3-D location and orientation requires a numerical
      technique because the equations are in nonclosed forms. The algorithm of tracking
      is implemented using MATLAB. Each calculation of the position along the target
      trajectory takes 30 ms, which makes the proposed system suitable for real-time
      tracking of the transponder for radiation assessment and delivery. An error of
      less than 2 mm is achieved in the demonstration. 

PMID- 23853369
TI  - Bacteria Growth Monitoring Through a Differential CMOS Capacitive Sensor.
AB  - In this paper, we present a bacteria growth monitoring technique using a
      complementary metal-oxide semiconductor capacitive sensor. The proposed platform
      features a differential capacitive readout architecture with two interdigitized
      reference and sensing electrodes. These electrodes are exposed to pure Luria
      Bertani (LB) medium and Escherichia Coli (E. Coli) bacteria suspended in the LB
      medium, respectively. In order to direct the solutions toward the electrodes, two
      microfluidic channels are implemented atop the electrodes through a direct-write
      assembly technique. We thereafter demonstrate and discuss the experimental
      results by using two different bacteria concentrations in the order of 10(6) and
      10(7) per 1 mL in the LB medium. 

PMID- 23853370
TI  - Prototype of video endoscopic capsule with 3-d imaging capabilities.
AB  - Wireless video capsules can now carry out gastroenterological examinations. The
      images make it possible to analyze some diseases during postexamination, but the
      gastroenterologist could make a direct diagnosis if the video capsule integrated
      vision algorithms. The first step toward in situ diagnosis is the implementation
      of 3-D imaging techniques in the video capsule. By transmitting only the
      diagnosis instead of the images, the video capsule autonomy is increased. This
      paper focuses on the Cyclope project, an embedded active vision system that is
      able to provide 3-D and texture data in real time. The challenge is to realize
      this integrated sensor with constraints on size, consumption, and processing,
      which are inherent limitations of the video capsule. We present the hardware and
      software development of a wireless multispectral vision sensor which enables the
      transmission of the 3-D reconstruction of a scene in real time. An FPGA-based
      prototype has been designed to show the proof of concept. Experiments in the
      laboratory, in vitro, and in vivo on a pig have been performed to determine the
      performance of the 3-D vision system. A roadmap towardthe integrated system is
      set out. 

PMID- 23853371
TI  - Digital Microfluidic Logic Gates and Their Application to Built-in Self-Test of
      Lab-on-Chip.
AB  - Dependability is an important system attribute for microfluidic lab-on-chip.
      Robust testing methods are therefore needed to ensure correct results. Previously
      proposed techniques for reading test outcomes and for pulse-sequence analysis are
      cumbersome and error prone. We present a built-in self-test (BIST) method for
      digital microfluidic lab-on-chip. This method utilizes digital microfluidic logic
      gates to implement the BIST architecture; AND, OR and NOT gates are used to
      compress multiple test-outcome droplets into a single droplet to facilitate
      detection with low overhead. These approaches obviate the need for capacitive
      sensing test-outcome circuits for analysis. We also apply the BIST architecture
      to a pin-constrained biochip design. A multiplexed bioassay protocol is used to
      evaluate the effectiveness of the proposed test method. 

PMID- 23853372
TI  - Programmable neural processing on a smartdust for brain-computer interfaces.
AB  - Brain-computer interfaces (BCIs) offer tremendous promise for improving the
      quality of life for disabled individuals. BCIs use spike sorting to identify the
      source of each neural firing. To date, spike sorting has been performed by either
      using off-chip analysis, which requires a wired connection penetrating the skull
      to a bulky external power/processing unit, or via custom application-specific
      integrated circuits that lack the programmability to perform different algorithms
      and upgrades. In this research, we propose and test the feasibility of performing
      on-chip, real-time spike sorting on a programmable smartdust, including feature
      extraction, classification, compression, and wireless transmission. A detailed
      power/performance tradeoff analysis using DVFS is presented. Our experimental
      results show that the execution time and power density meet the requirements to
      perform real-time spike sorting and wireless transmission on a single neural
      channel. 

PMID- 23853373
TI  - CMOS Optoelectronic Lock-In Amplifier With Integrated Phototransistor Array.
AB  - We describe the design and development of an optoelectronic lock-in amplifier
      (LIA) for optical sensing and spectroscopy applications. The prototype amplifier
      is fabricated using Taiwan Semiconductor Manufacturing Co. complementary metal
      oxide semiconductor 0.35-MUm technology and uses a phototransistor array (total
      active area is 400 MUm * 640MUm) to convert the incident optical signals into
      electrical currents. The photocurrents are then converted into voltage signals
      using a transimpedance amplifier for subsequent convenient signal processing by
      the LIA circuitry. The LIA is optimized to be operational at 20-kHz modulation
      frequency but is operational in the frequency range from 13 kHz to 25 kHz. The
      system is tested with a light-emitting diode (LED) as the light source. The noise
      and signal distortions are suppressed with filters and a phase-locked loop (PLL)
      implemented in the LIA. The output dc voltage of the LIA is proportional to the
      incident optical power. The minimum measured dynamic reserve and sensitivity are
      1.31 dB and 34 mV/MUW, respectively. The output versus input relationship has
      shown good linearity. The LIA consumes an average power of 12.79 mW with a 3.3-V
      dc power supply. 

PMID- 23853374
TI  - Mechanically flexible wireless multisensor platform for human physical activity
      and vitals monitoring.
AB  - Practical usability of the majority of current wearable body sensor systems for
      multiple parameter physiological signal acquisition is limited by the multiple
      physical connections between sensors and the data-acquisition modules. In order
      to improve the user comfort and enable the use of these types of systems on
      active mobile subjects, we propose a wireless body sensor system that
      incorporates multiple sensors on a single node. This multisensor node includes
      signal acquisition, processing, and wireless data transmission fitted on multiple
      layers of a thin flexible substrate with a very small footprint. Considerations
      for design include size, form factor, reliable body attachment, good signal
      coupling, low power consumption, and user convenience. The prototype device
      measures 55 15 mm and is 3 mm thick. The unit is attached to the patient's chest,
      and is capable of performing simultaneous measurements of parameters, such as
      body motion, activity intensity, tilt, respiration, cardiac vibration, cardiac
      potential (ECG), heart rate, and body surface temperature. In this paper, we
      discuss the architecture of this system, including the multisensor hardware, the
      firmware, a mobile-phone receiver unit, and assembly of the first proof-of
      concept prototype. Preliminary performance results on key elements of the system,
      such as power consumption, wireless range, algorithm efficiency, ECG signal
      quality for heart-rate calculations, as well as synchronous ECG and body activity
      signals are also presented. 

PMID- 23853375
TI  - A tunable biquad switched-capacitor amplifier-filter for neural recording.
AB  - With the emerging interest in local field potentials (LFPs) as input signals for
      brain-machine interfaces, there is a need for integrated circuits capable of
      amplifying spikes and LFPs. A two-stage complementary metal-oxide semiconductor
      (CMOS) amplifier-filter has been implemented with 0.18-MUm CMOS for simultaneous,
      multimodal recording of extracellular unit spikes and LFPs. For the frequency
      tuning and the reduction of the 1/f noise, it employs a switched-capacitor
      technique. The filter bandwidth is reconfigurable by using a different sampling
      clock frequency. The prototype amplifier has gains of 19.1 dB and 37.5 dB for low
      pass only filter and cascaded filter, respectively. With a 100-kHz sampling
      frequency, the equivalent input noise spectral density is 38.8 nV/?Hz while the
      total power consumption is 69 MUW with a 1.6-V supply, including clock generation
      and biasing occupying an area of 44 * 148 MUm(2). 

PMID- 23853376
TI  - Neural dynamics in reconfigurable silicon.
AB  - A neuromorphic analog chip is presented that is capable of implementing massively
      parallel neural computations while retaining the programmability of digital
      systems. We show measurements from neurons with Hopf bifurcations and integrate
      and fire neurons, excitatory and inhibitory synapses, passive dendrite cables,
      coupled spiking neurons, and central pattern generators implemented on the chip.
      This chip provides a platform for not only simulating detailed neuron dynamics
      but also uses the same to interface with actual cells in applications such as a
      dynamic clamp. There are 28 computational analog blocks (CAB), each consisting of
      ion channels with tunable parameters, synapses, winner-take-all elements, current
      sources, transconductance amplifiers, and capacitors. There are four other CABs
      which have programmable bias generators. The programmability is achieved using
      floating gate transistors with on-chip programming control. The switch matrix for
      interconnecting the components in CABs also consists of floating-gate
      transistors. Emphasis is placed on replicating the detailed dynamics of
      computational neural models. Massive computational area efficiency is obtained by
      using the reconfigurable interconnect as synaptic weights, resulting in more than
      50 000 possible 9-b accurate synapses in 9 mm(2). 

PMID- 23853377
TI  - Dynamics and bifurcations in a silicon neuron.
AB  - In this paper, the nonlinear dynamical phenomenon associated with a silicon
      neuron are described. The neuron has one transient sodium (activating and
      inactivating) channel and one activating potassium channel. These channels do not
      model specific equations; instead they directly mimic the desired voltage clamp
      responses. This allows us to create silicon structures that are very compact (six
      transistors and three capacitors) with activation and inactivation parameters
      being tuned by floating-gate (FG) transistors. Analysis of the bifurcation
      conditions allow us to identify regimes in the parameter space that are desirable
      for biasing the circuit. We show a subcritical Hopf-bifurcation which is
      characteristic of class 2 excitability in Hodgkin-Huxley (H-H) neurons. We also
      show a Hopf bifurcation at higher values of stimulating current, a phenomenon
      also observed in real neurons and termed excitation block. The phenomenon of post
      inhibitory rebound and frequency preference are displayed and intuitive
      explanations based on the circuit are provided. The compactness and low-power
      nature of the circuit shall allow us to integrate a large number of these neurons
      on a chip to study complicated network behavior. 

PMID- 23853378
TI  - A low-cost implantable near-infrared imaging system of spinal cord activity in
      the cat.
AB  - A low-cost device using diffuse optical imaging (DOI) for measuring in vivo
      hemodynamic changes in the spinal cord has been developed. The proposed system is
      aimed at monitoring for the first time real-time hemodynamic changes associated
      with intraspinal rhythmic motor activity monitored by electroneurogram (ENG)
      evoked in paralyzed cats (fictive locomotion). The device contains the emitting
      and collecting probes within a saddle that fits over a vertebra and has been
      developed with discrete component circuits. Experiments performed in two acutely
      decerebrate and paralyzed cats confirm a noticeable and reproducible hemodynamic
      response during episodes of fictive locomotion. The device is designed so that it
      could be implanted chronically. In the future, a multi-implant imaging platform
      could measure long-term hemodynamic changes in the spinal cord. 

PMID- 23853379
TI  - Power-efficient cross-correlation beat detection in electrocardiogram analysis
      using bitstreams.
AB  - In this paper, we present a novel cross-correlator chip suitable for "smart" ECG
      electrodes. Sophisticated QRS-detection is feasible exploring multicomponent
      based cross-correlation and by exploiting the simplicity offered by bitstream
      processing. The chip is evaluated using real ECG signals as an example
      application. Power-efficient running cross correlation is obtained with novel
      asynchronous circuit solutions consuming approximately 730 MU W while processing
      ECG data sampled at a rate of 250 Hz. The implemented generic cross-correlator
      may be explored for other pattern-matching applications in wireless sensor
      networks or other low-power applications. 

PMID- 23853380
TI  - 3-D System-on-System (SoS) Biomedical-Imaging Architecture for Health-Care
      Applications.
AB  - This paper presents the implementation of a 3-D architecture for a biomedical
      imaging system based on a multilayered system-on-system structure. The
      architecture consists of a complementary metal-oxide semiconductor image sensor
      layer, memory, 3-D discrete wavelet transform (3D-DWT), 3-D Advanced Encryption
      Standard (3D-AES), and an RF transmitter as an add-on layer. Multilayer silicon
      (Si) stacking permits fabrication and optimization of individual layers by
      different processing technology to achieve optimal performance. Utilization of
      through silicon via scheme can address required low-power operation as well as
      high-speed performance. Potential benefits of 3-D vertical integration include an
      improved form factor as well as a reduction in the total wiring length,
      multifunctionality, power efficiency, and flexible heterogeneous integration. The
      proposed imaging architecture was simulated by using Cadence Spectre and Synopsys
      HSPICE while implementation was carried out by Cadence Virtuoso and Mentor
      Graphic Calibre. 

PMID- 23853381
TI  - A Vertically Integrated CMOS Microsystem for Time-Resolved Fluorescence Analysis.
AB  - We describe a two-chip micro-scale time-resolved fluorescence analyzer
      integrating excitation, detection, and filtering. A new 8*8 array of drivers
      realized in standard low-voltage 0.35-MUm complementary metal-oxide semiconductor
      is bump-bonded to AlInGaN blue micro-pixellated light-emitting diodes (micro
      LEDs). The array is capable of producing sample excitation pulses with a width of
      777 ps (FWHM), enabling short lifetime fluorophores to be investigated. The
      fluorescence emission is detected by a second, vertically-opposed 16 * 4 array of
      single-photon avalanche diodes (SPADs) fabricated in 0.35-MUm high-voltage CMOS
      technology with in-pixel time-gated photon counting circuitry. Captured chip data
      are transferred to a PC for further processing, including histogramming, lifetime
      extraction, calibration and background/noise compensation. This constitutes the
      smallest reported solid-state microsystem for fluorescence decay analysis,
      replacing lasers, photomultiplier tubes, bulk optics, and discrete electronics.
      The system is demonstrated with measurements of fluorescent colloidal quantum dot
      and Rhodamine samples. 

PMID- 23853382
TI  - Development and in vivo Demonstration of CMOS-Based Multichip Retinal Stimulator
      With Simultaneous Multisite Stimulation Capability.
AB  - A complementary metal-oxide semiconductor (CMOS)-based multichip flexible neural
      stimulator for retinal prostheses was developed. The multichip retinal stimulator
      is capable of simultaneous multisite stimulation. An on-chip stimulation
      generator was implemented on the "unit chip," which is the core device of the
      multichip retinal stimulator. The performance of the CMOS circuitry was
      characterized. A new device structure and packaging process was developed. The in
      vivo retinal stimulation on a rabbit's retina was successfully performed and the
      multisite stimulation functionality was confirmed. 

PMID- 23853383
TI  - A Fully Integrated RF-Powered Contact Lens With a Single Element Display.
AB  - We present progress toward a wirelessly-powered active contact lens comprised of
      a transparent polymer substrate, loop antenna, power harvesting IC, and micro
      LED. The fully integrated radio power harvesting and power management system was
      fabricated in a 0.13 MUm CMOS process with a total die area of 0.2 mm(2). It
      utilizes a small on-chip capacitor for energy storage to light up a micro-LED
      pixel. We have demonstrated wireless power transfer at 10 cm distance using the
      custom IC and on-lens antenna. 

PMID- 23853384
TI  - A wireless narrowband imaging chip for capsule endoscope.
AB  - This paper presents a dual-mode capsule gastrointestinal endoscope device. An
      endoscope combined with a narrowband image (NBI), has been shown to be a superior
      diagnostic tool for early stage tissue neoplasms detection. Nevertheless, a
      wireless capsule endoscope with the narrowband imaging technology has not been
      presented in the market up to now. The narrowband image acquisition and power
      dissipation reduction are the main challenges of NBI capsule endoscope. In this
      paper, we present the first narrowband imaging capsule endoscope that can assist
      clinical doctors to effectively diagnose early gastrointestinal cancers, profited
      from our dedicated dual-mode complementary metal-oxide semiconductor (CMOS)
      sensor. The dedicated dual-mode CMOS sensor can offer white-light and narrowband
      images. Implementation results show that the proposed 512 * 512 CMOS sensor
      consumes only 2 mA at a 3-V power supply. The average current of the NBI capsule
      with an 8-Mb/s RF transmitter is nearly 7 ~ 8 mA that can continuously work for 6
      ~ 8 h with two 1.5-V 80-mAh button batteries while the frame rate is 2 fps.
      Experimental results on backside mucosa of a human tongue and pig's small
      intestine showed that the wireless NBI capsule endoscope can significantly
      improve the image quality, compared with a commercial-of-the-shelf capsule
      endoscope for gastrointestinal tract diagnosis. 

PMID- 23853385
TI  - A New Individually Addressable Micro-LED Array for Photogenetic Neural
      Stimulation.
AB  - Here, we demonstrate the use of a micro light emitting diode (LED) array as a
      powerful tool for complex spatiotemporal control of photosensitized neurons. The
      array can generate arbitrary, 2-D, excitation patterns with millisecond and
      micrometer resolution. In particular, we describe an active matrix control
      address system to allow simultaneous control of 256 individual micro LEDs. We
      present the system optically integrated into a microscope environment and patch
      clamp electrophysiology. The results show that the emitters have sufficient
      radiance at the required wavelength to stimulate neurons expressing
      channelrhodopsin-2 (ChR2). 

PMID- 23853386
TI  - Measurement Properties of a Park Use Questionnaire.
AB  - We determined the criterion validity and test-retest reliability of a brief park
      use questionnaire. From five US locations, 232 adults completed a brief survey
      four times and wore a global positioning system (GPS) monitor for three weeks. We
      assessed validity for park visits during the past week and during a usual week by
      examining agreement between frequency and duration of park visits reported in the
      questionnaire to the GPS monitor results. Spearman correlation coefficients (SCC)
      were used to measure agreement. For past week park visit frequency and duration,
      the SCC were 0.62-0.65 and 0.62-0.67, respectively. For usual week park visit
      frequency and duration, the SCC were 0.40-0.50 and 0.50-0.53, respectively. Usual
      park visit frequency reliability was 0.78-0.88 (percent agreement 69%-82%) and
      usual park visit duration was 0.75-0.84 (percent agreement 64%-73%). These
      results suggest that the questionnaire to assess usual and past week park use had
      acceptable validity and reliability.

PMID- 23853387
TI  - Multiscale model of platelet translocation and collision.
AB  - The tethering of platelets on the injured vessel surface mediated by glycoprotein
      Ibalpha (GPIbalpha) - Von Willebrand factor (vWF) bonds, as well as the
      interaction between flowing platelets and adherent platelets, are two key events
      that take place immediately following blood vessel injury. This early-stage
      platelet deposition and accumulation triggers the initiation of hemostasis, a
      self-defensive mechanism to prevent the body from excessive blood loss. To
      understand and predict this complex process, one must integrate experimentally
      determined information on the mechanics and biochemical kinetics of participating
      receptors over very small time frames (1-1000 us) and length scales (10-100 nm),
      to collective phenomena occurring over seconds and tens of microns. In the
      present study, a unique three dimensional multiscale computational model,
      platelet adhesive dynamics (PAD), was applied to elucidate the unique physics of
      (i) a non-spherical, disk-shaped platelet interacting and tethering onto the
      damaged vessel wall followed by (ii) collisional interactions between a flowing
      platelet with a downstream adherent platelet. By analyzing numerous simulations
      under different physiological conditions, we conclude that the platelet's unique
      spheroid-shape provides heterogeneous, orientation-dependent translocation
      (rolling) behavior which enhances cell-wall interactions. We also conclude that
      platelet-platelet near field interactions are critical for cell-cell
      communication during the initiation of microthrombi. The PAD model described here
      helps to identify the physical factors that control the initial stages of
      platelet capture during this process.

PMID- 23853388
TI  - Temporal Multiscale Approach for Nanocarrier Motion with Simultaneous Adhesion
      and Hydrodynamic Interactions in Targeted Drug Delivery.
AB  - We present a fluctuating hydrodynamics approach and a hybrid approach combining
      fluctuating hydrodynamics with generalized Langevin dynamics to resolve the
      motion of a nanocarrier when subject to both hydrodynamic interactions and
      adhesive interactions. Specifically, using these approaches, we compute
      equilibrium probability distributions at constant temperature as well as velocity
      autocorrelation functions of the nanocarrier subject to thermal motion in a
      quiescent Newtonian fluid medium, when tethered by a harmonic spring force
      mimicking a tether due to a single receptor-ligand bond. We demonstrate that the
      thermal equipartition of translation, rotation, and spring degrees of freedom are
      preserved by our formalism while simultaneously resolving the nature of the
      hydrodynamic correlations. Additionally, we evaluate the potential of mean force
      (or free energy density) along a specified reaction coordinate to faciltate
      extensive conformational sampling of the nanocarrier motion. We show that our
      results are in excellent agreement with analytical results and Monte Carlo
      simulations, thereby validating our methodologies. The frameworks we have
      presented provide a comprehensive platform for temporal multiscale modeling of
      hydrodynamic and microscopic interactions mediating nanocarrier motion and
      adhesion in vascular targeted drug delivery.

PMID- 23853389
TI  - Plants do not count... or do they? New perspectives on the universality of
      senescence.
AB  - 1. Senescence, the physiological decline that results in decreasing survival
      and/or reproduction with age, remains one of the most perplexing topics in
      biology. Most theories explaining the evolution of senescence (i.e. antagonistic
      pleiotropy, accumulation of mutations, disposable soma) were developed decades
      ago. Even though these theories have implicitly focused on unitary animals, they
      have also been used as the foundation from which the universality of senescence
      across the tree of life is assumed. 2. Surprisingly, little is known about the
      general patterns, causes and consequences of whole-individual senescence in the
      plant kingdom. There are important differences between plants and most animals,
      including modular architecture, the absence of early determination of cell lines
      between the soma and gametes, and cellular division that does not always shorten
      telomere length. These characteristics violate the basic assumptions of the
      classical theories of senescence and therefore call the generality of senescence
      theories into question. 3. This Special Feature contributes to the field of whole
      individual plant senescence with five research articles addressing topics ranging
      from physiology to demographic modelling and comparative analyses. These articles
      critically examine the basic assumptions of senescence theories such as age
      specific gene action, the evolution of senescence regardless of the organism's
      architecture and environmental filtering, and the role of abiotic agents on
      mortality trajectories. 4.Synthesis. Understanding the conditions under which
      senescence has evolved is of general importance across biology, ecology,
      evolution, conservation biology, medicine, gerontology, law and social sciences.
      The question 'why is senescence universal or why is it not?' naturally calls for
      an evolutionary perspective. Senescence is a puzzling phenomenon, and new
      insights will be gained by uniting methods, theories and observations from formal
      demography, animal demography and plant population ecology. Plants are more
      amenable than animals to experiments investigating senescence, and there is a
      wealth of published plant demographic data that enable interpretation of
      experimental results in the context of their full life cycles. It is time to make
      plants count in the field of senescence.

PMID- 23853391
TI  - Examining the Initiation of the Polymerization Mechanism and Network Development
      in Aromatic Polybenzoxazines.
AB  - Three bis-benzoxazine monomers based on the aniline derivatives of bisphenol A
      (BA-a), bisphenol F (BF-a), and 3,3'-thiodiphenol (BT-a) are examined using a
      variety of spectroscopic, chromatographic, and thermomechanical techniques. The
      effect on the polymerization of the monomers is compared using two common
      compounds, 3,3'-thiodiphenol (TDP) and 3,3'-thiodipropionic acid (TDA), at a
      variety of loadings. It is found that the diacid has a greater effect on reducing
      the onset of polymerization and increasing cross-link density and Tg for a given
      benzoxazine. However, the addition of >5 wt % of the diacid had a detrimental
      effect on the cross-link density, Tg, and thermal stability of the polymer. The
      kinetics of the polymerization of BA-a were found to be well described using an
      autocatalytic model for which values of n = 1.64 and m = 2.31 were obtained for
      the early and later stages of reaction (activation energy = 81 kJ/mol). Following
      recrystallization the same monomer yielded values n = 1.89, m = 0.89, and Ea = 94
      kJ/mol (confirming the influence of higher oligomers on reactivity). The choice
      of additive (in particular the magnitude of its pKa) appears to influence the
      nature of the network formation from a linear toward a more clusterlike growth
      mechanism.

PMID- 23853390
TI  - Global migration can lead to stronger spatial selection than local migration.
AB  - The outcome of evolutionary processes depends on population structure. It is well
      known that mobility plays an important role in affecting evolutionary dynamics in
      group structured populations. But it is largely unknown whether global or local
      migration leads to stronger spatial selection and would therefore favor to a
      larger extent the evolution of cooperation. To address this issue, we quantify
      the impacts of these two migration patterns on the evolutionary competition of
      two strategies in a finite island model. Global migration means that individuals
      can migrate from any one island to any other island. Local migration means that
      individuals can only migrate between islands that are nearest neighbors; we study
      a simple geometry where islands are arranged on a one-dimensional, regular cycle.
      We derive general results for weak selection and large population size. Our key
      parameters are: the number of islands, the migration rate and the mutation rate.
      Surprisingly, our comparative analysis reveals that global migration can lead to
      stronger spatial selection than local migration for a wide range of parameter
      conditions. Our work provides useful insights into understanding how different
      mobility patterns affect evolutionary processes.

PMID- 23853392
TI  - A Euclidean Perspective on the Unfolding of Azurin: Spatial Correlations.
AB  - We investigate the stability to structural perturbation of Pseudomonas aeruginosa
      azurin using a previously developed geometric model. Our analysis considers
      Ru(2,2',6',2"-terpyridine)(1,10-phenanthroline)(His83)-labeled wild-type azurin
      and five variants with mutations to Cu-ligating residues. We find that in the
      early stages of unfolding, the beta-strands exhibit the most structural
      stability. The conserved residues comprising the hydrophobic core are dislocated
      only after nearly complete unfolding of the beta-barrel. Attachment of the Ru
      complex at His83 does not destabilize the protein fold, despite causing some
      degree of structural rearrangement. Notably, replacing the Cys112 and/or Met121
      Cu ligands does not affect the conformational integrity of the protein. Notably,
      these results are in accord with experimental evidence, as well as molecular
      dynamics simulations of the denaturation of azurin.

PMID- 23853393
TI  - Living Beyond the Other.
AB  - This article attempts to bring philosophy to clinical psychological practice by
      applying philosophical concepts to autobiographical experience. Through
      reflective engagement with personal narratives, the author tells three personal
      stories to illustrate ways in which the concept of Dasein in the philosophy of
      Martin Heidegger and Emmanuel Levinas's development of an ethical responsibility
      to the Other, in tandem with thanatology, helped the author come to terms with
      existential dilemmas evoked by the deaths of others.

PMID- 23853394
TI  - Assessment of Tri- and Hexavalent Chromium Phytotoxicity on Oats (Avena sativa
      L.) Biomass and Content of Nitrogen Compounds.
AB  - The purpose of this study was to determine the effect of soil contamination with
      tri- and hexavalent chromium and soil application of compost, zeolite, and CaO on
      the mass of oats and content of nitrogen compounds in different organs of oats.
      The oats mass and content of nitrogen compounds in the crop depended on the type
      and dose of chromium and alleviating substances incorporated to soil. In the
      series without neutralizing substances, Cr(VI), unlike Cr(III), had a negative
      effect on the growth and development of oats. The highest doses of Cr(VI) and
      Cr(III) stimulated the accumulation of total nitrogen but depressed the content
      of N-NO3- in most of organs of oats. Among the substances added to soil in order
      to alleviate the negative impact of Cr (VI) on the mass of plants, compost had a
      particularly beneficial effect on the growth and development of oats. The
      application of compost, zeolite, and CaO to soil had a stronger effect on the
      content of nitrogen compounds in grain and straw than in roots. Soil enrichment
      with either of the above substances usually raised the content of nitrogen
      compounds in oats grain and straw, but decreased it in roots.

PMID- 23853395
TI  - Warning signals confer advantage to prey in competition with predators:
      bumblebees steal nests from insectivorous birds.
AB  - Aposematic (warning) signals of prey help predators to recognize the defended
      distasteful or poisonous prey that should be avoided. The evolution of
      aposematism in the context of predation has been in the center of modern ecology
      for a long time. But, the possible roles of aposematic signals in other
      ecological contexts have been largely ignored. Here we address the role of
      aposematic signals in competition between prey and predators. Bumblebees use
      visual and auditory aposematic signals to warn predators about their defenses.
      For 2 years, we observed competition for nestboxes between chemically defended
      insects, Bombus ardens (and possibly also Bombus ignitus), and cavity nesting
      birds (Parus minor and Poecile varius). Bumblebees settled in 16 and 9 % of
      nestboxes (in 2010 and 2011 breeding seasons, respectively) that contained bird
      nests at the advanced stage of nest building or at the stage of egg laying.
      Presence of bumblebees prevented the birds from continuing the breeding
      activities in the nestboxes, while insects took over the birds' nests (a form of
      kleptoparasitism). Playback experiments showed that the warning buzz by
      bumblebees contributed to the success in ousting the birds from their nests. This
      demonstrates that aposematic signals may be beneficial also in the context of
      resource competition.

PMID- 23853397
TI  - Is it necessary to remove submandibular glands in squamous cell carcinomas of the
      oral cavity?
AB  - The aim of this study was to determine the frequency and the mechanism of
      submandibular gland (SMG) involvement in oral cavity squamous cell carcinomas
      (OCSCC), and to discuss the necessity of extirpation of the gland. The authors
      investigated and analyzed the retrospective charts of 236 patients who underwent
      surgery for OCSCC over a 10-year period and the pathology reports of 294 neck
      dissections with SMG removal. SMG involvement was evident in 13 cases (4%). Eight
      cases were due to direct invasion, which was the most common mechanism. Four
      cases had infiltration from a metastatic periglandular lymphadenopathy, and in 1
      case, metastatic disease was confirmed. The tongue and floor of the mouth were
      the most frequent primary sites associated with SMG involvement. The study found
      no bilateral cases, and in 135 SMG specimens benign pathologies were detected.
      Involvement of the SMG in OCSCC is not frequent. It is appropriate to preserve
      the gland unless the primary tumour or metastatic regional lymphadenopathy is
      adherent to the gland. 

PMID- 23853398
TI  - Minimizing shoulder syndrome with intra-operative spinal accessory nerve
      monitoring for neck dissection.
AB  - The objective of this study was to analyze the safety and results of intra
      operative SAN (spinal accessary nerve) monitoring during selective neck
      dissection, with emphasis on shoulder syndrome. Twenty-five consecutive patients
      with head and neck cancer were studied. Selective neck dissection was performed
      by a single clinical fellow under the supervision of the department chief using
      an intra-operative SAN monitor. Electrophysiological data were recorded after
      initial identification of the SAN and continued until just before closure.
      Electromyographic evaluation was carried out to assess SAN function one month
      postoperatively. Shoulder disability was also evaluated at this time using a
      questionnaire for shoulder syndrome (shrug, flexion, abduction, winging, and
      pain). No patients had postoperative shoulder syndrome involving shrug, flexion,
      abduction, or winging. Twenty-two of the 25 (88%) patients had shoulder pain, but
      the average pain score was low (2.3 +/- 1.3). No patients had neck recurrence
      during at least 1 year of follow up. By using nerve monitoring during selective
      neck dissection, no patient developed significant "shoulder syndrome", with the
      exception of slight pain. 

PMID- 23853396
TI  - New insights into human papillomavirus-associated head and neck squamous cell
      carcinoma.
AB  - Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma
      (HNSCC) is an entity with peculiar clinical and molecular characteristics, which
      mainly arises from the reticulated epithelium lining the crypts of the palatine
      tonsils and the base of the tongue. The only head and neck site with a definite
      etiological association between persistent high-risk (HR) HPV infection and
      development of SCC is the oropharynx. HPV-positive malignancies represent 5-20%
      of all HNSCCs and 40-90% of those arising from the oropharynx, with widely
      variable rates depending on the geographic area, population, relative prevalence
      of environment-related SCC and detection assay. HPV-16 is by far the most common
      HR HPV genotype detected in oropharyngeal SCC (OPSCC), and the only definitely
      carcinogenic genotype for the head and neck region. Patients with HPV-induced
      OPSCC are more likely to be middle-aged white men, non-smokers, non-drinkers or
      mild to moderate drinkers, with higher socioeconomic status and better
      performance status than subjects with HPV-unrelated SCC. HPV-induced HNSCCs are
      often described as non-keratinizing, poorly differentiated or basaloid
      carcinomas, and are diagnosed in earlier T-category with a trend for a more
      advanced N-category, with cystic degeneration, than the HPV-unrelated carcinomas.
      HPV positivity is associated with better response to treatment and modality
      independent survival benefit. Treatment selection in HPV-related oropharyngeal
      carcinoma is becoming a critical issue, and although there is no evidence from
      randomized, controlled trials to support a treatment de-escalation in HPV
      positive SCC, some investigators argue that intensive combined modality
      strategies may represent an overtreatment. 

PMID- 23853399
TI  - Transmastoid approach to repair meningoencephalic herniation in the middle ear.
AB  - Meningoencephalic herniation (MEH) in the middle ear and mastoid is a rare
      pathological entity with possible life-threatening complications. We treated 24
      patients with a trans-mastoid approach, and the bony defect was closed by
      heterologous materials positioned in a multilayer fashion. The cause of the bony
      defect were chronic otitis media with cholesteatoma, iatrogenic, spontaneous and
      post-traumatic. The major presenting symptoms were meningitis, headache,
      conductive hearing loss, cerebrospinal fluid (CSF leak), neurologic deficit and
      pneumoencephalus, and stenosis of a canal wall down cavity. During follow-up, no
      patient developed complications due to surgery or related to the pathology, and
      imaging showed a stable occlusion of the bony defect. Different surgical
      treatments have been proposed to repair MEH, and the choice is based on the
      localization and size of the bony defect, preoperative auditory function and the
      presence of a coexisting pathology. We propose the use of collagenous membranes
      and bone substitutes for reconstruction of the floor of the middle fossa. 

PMID- 23853400
TI  - Endoscopic expanded endonasal approach: preliminary experience with the new 3D
      endoscope.
AB  - The recent introduction of the 3D endoscope for endonasal surgery has been
      welcomed because of its promise to overcome the main limitation of endoscopy,
      namely the lack of stereoscopic vision. This innovation particularly regarded the
      most complex transnasal surgery of the skull base. We therefore discuss our early
      experience as ENT surgeons with the use of a purely 3D endoscopic expanded
      endonasal approach for supradiaphragmatic lesions in 10 consecutive patients.
      This article will focus on the surgical technique, the complications, the
      outcome, and more importantly the advantages and limitations of the new device.
      We believe that the new 3D system shows its main drawback when surgery is
      conducted in the narrow nasal spaces. Nevertheless, the improved knowledge of the
      three-dimensional nasal anatomy enabled the ENT surgeon to perform a more
      selective demolition of the nasal structures even in the anterior part of the
      nose. The depth perception obtained with the 3D system also permitted a better
      understanding of the plasticity of the surgical defects, increasing the
      confidence to perform successful skull base plasties. We believe that, for both
      the ENT surgeon and the neurosurgeon, the expanded endonasal approach is the main
      indication for this exciting tool, although larger prospective studies are needed
      to determine the equality to the 2D HD endoscope in oncological terms. 

PMID- 23853401
TI  - Endoscopic management of paediatric antrochoanal polyp: our experience.
AB  - Antrochoanal polyp is a benign polypoid lesion arising from the oedematous mucosa
      of the maxillary sinus and extending through the maxillary ostium into the nose.
      In children, it constitutes 33% of all nasal polyps. Surgery is the usual
      treatment for antrochoanal polyps. The primary aim of treatment for antrochoanal
      polyp is complete removal with total clearance of the maxillary sinus. Herein, we
      present 36 cases of children with antrochoanal polyps (ACPs). All patients
      underwent preoperative radiological assessment by CT scan. All patients were
      subjected to uncinectomy and modified type III maxillary sinusotomy of the
      maxillary ostium for removal of the ACPs. Modified type III maxillary sinusotomy
      was performed by dilatation of the ostium of the maxillary sinus posteriorly,
      inferiorly and anteriorly. The most frequent presenting complaint was unilateral
      nasal obstruction, followed by rhinorrhoea. In 28 children, the polyps passed
      through the main ostium, while in 5 patients the polyp passed through the
      accessory ostium. In 3 children, the origin could not assessed. The antral
      portion of the ACP was cystic in 3 patients and polypoidal in 33 cases.
      Recurrence was reported in 4 patients (11.1%) that were subjected to revision
      endoscopic sinus surgery. The follow-up period ranged from 12 months to 5 years
      with a mean of 3.5 years. 

PMID- 23853402
TI  - Tympanometric findings in superior semicircular canal dehiscence syndrome.
AB  - The diagnostic role of audio-impedancemetry in superior semicircular canal
      dehiscence (SSCD) disease is well known. In particular, since the first reports,
      the presence of evoked acoustic reflexes has represented a determining
      instrumental exhibit in differential diagnosis with other middle ear pathologies
      that are responsible for a mild-low frequencies air-bone gap (ABG). Even though
      high resolution computed tomography (HRCT) completed by parasagittal reformatted
      images still represents the diagnostic gold standard, several instrumental tests
      can support a suspect of labyrinthine capsule dehiscence when "suggestive"
      symptoms occur. Objective and subjective audiometry often represents the starting
      point of the diagnostic course aimed at investigating the cause responsible for
      the so-called "intra-labyrinthine conductive hearing loss". The purpose of this
      study is to evaluate the role of tympanometry, in particular of the inter-aural
      asymmetry ratio in peak compliance as a function of different mild-low
      frequencies ABG on the affected side, in the diagnostic work-up in patients with
      unilateral SSCD. The working hypothesis is that an increase in admittance of the
      "inner-middle ear" conduction system due to a "third mobile window" could be
      detected by tympanometry. A retrospective review of the clinical records of 45
      patients with unilateral dehiscence selected from a pool of 140 subjects
      diagnosed with SSCD at our institution from 2003 to 2011 was performed. Values of
      ABG amplitude on the dehiscent side and tympanometric measurements of both ears
      were collected for each patient in the study group (n = 45). An asymmetry between
      tympanometric peak compliance of the involved side and that of the contralateral
      side was investigated by calculating the inter-aural difference and the asymmetry
      ratio of compliance at the eardrum. A statistically significant correlation (p =
      0.015 by Fisher's test) between an asymmetry ratio >= 14% in favour of the
      pathologic ear and an ABG > 20 dB nHL on the same side was found. When
      "evocative" symptoms of SSCD associated with important ABG occur, the inter-aural
      difference in tympanometric peak compliance at the eardrum in favour of the
      "suspected" side could suggest an intra-labyrinthine origin for the asymmetry.
      Tympanometry would thus prove to be a useful instrument in clinical-instrumental
      diagnosis of SSCD in detection of cases associated with alterations of inner ear
      impedance. 

PMID- 23853404
TI  - The "Barbed Roman Blinds" technique: a step forward.

PMID- 23853403
TI  - Reliability of the Italian INFVo scale and correlations with objective measures
      and VHI scores.
AB  - The objective of this study was to evaluate the reliability of the INFVo scale
      and its relationship with objective measures and VHI scores in 40 native Italian
      speaking patients with substitution voice. The maximum phonation time (MPT),
      diadochokinesis (DDK) of the three syllabic sequence [pa/ta/ka], reading of a
      passage and a single word repetition test were recorded. Each patient completed
      the Italian version of the VHI. Three speech-language pathologists blindly rated
      the recordings using the auditory perceptual INFVo scale; one listened and
      assessed the voice recording twice. The INFVo intra- and inter-rater reliability
      reached good values. Strong to moderate correlations between the INFVo scale
      scores and MPT, DDK, distortions in the repetition test, speech rate during
      reading and the functional subscale of the VHI were found. In conclusion, the
      INFVo scale is a reliable tool and can be recommended for the perceptual
      assessment of substitution voices in Italian speaking patients. 

PMID- 23853405
TI  - The park-bench position in cervico-facial reconstructive surgery: a technical
      note.
AB  - Resection and simultaneous reconstruction with free flaps of wide tumours of the
      scalp and posterior neck region are difficult to perform through a single
      surgical approach. In such cases, the park-bench position - a lateral oblique
      position - could allow simultaneous resection and reconstruction of tumours of
      the scalp and occipital region without changing the patient's position. In the
      case described here, this position was used to treat microcystic adnexal
      carcinoma in a patient who presented with three scalp lesions and a lesion of the
      right scapular region. This arrangement allowed both resection and reconstruction
      with a microvascular flap without changing the patient's position, as a result of
      being able to find neck vessels suitable for microanastomosis. Reconstruction was
      carried out using a right latissimus dorsi myogenous and subcutaneous flap, and
      anastomoses were created between the thoracodorsal artery and vein, and the
      transverse cervical artery and vein. In this position, transverse cervical
      vessels are well placed, with good exposure, and are in an optimal location for
      use in microvascular surgery. At 8 months post-reconstruction, the patient was in
      good condition without local recurrence or distant metastases, and the flap
      showed a good lining and contour. In conclusion, the park-bench position
      facilitates surgical excision, flap harvesting and microsurgery in the same
      patient position. 

PMID- 23853406
TI  - Focused tight dressing does not prevent cochlear implant magnet migration under
      1.5 Tesla MRI.
AB  - We report a retrospective case of inner magnet migration, which occurred after
      1.5 Tesla MRI scanning in an adult recipient of a bilateral cochlear implant (CI)
      despite a focused head dressing. The patient, bilaterally implanted with Nucleus
      5 CIs (Cochlear LTD, Sydney, Australia), underwent a 1.5 Tesla cholangio-MRI scan
      for biliary duct pathology. In subsequent days, a focal skin alteration appeared
      over the left inner coil. Plain skull radiographs showed partial magnet migration
      on the left side. Surgical exploration confirmed magnet twisting; the magnet was
      effectively repositioned. Left CI performance was restored to pre-migration
      level. The wound healed without complications. Thus, focused dressing does not
      prevent magnet migration in CI recipients undergoing 1.5 Tesla MRI. All patients
      should be counselled on this potential complication. A minor surgical procedure
      is required to reposition the magnet. Nevertheless, timely diagnosis is necessary
      to prevent skin breakdown and subsequent device contamination. Plain skull
      radiograph is very effective in identifying magnet twisting; it should be
      performed systematically after MRI or minimally on all suspected cases. 

PMID- 23853407
TI  - Lingual schwannoma: case report and review of the literature.
AB  - Schwannomas are benign, encapsulated, slow-growing and usually solitary tumours
      originating from Schwann cells of the peripheral nerve sheath. Approximately 25
      40% of cases are seen in the head and neck region, of which 1% in the oral
      cavity. We report a rare case of lingual schwannoma in a young woman who was
      treated with complete transoral excision, and also review the literature of the
      past two decades, analyzing epidemiological and clinical data of the 35 cases
      reported. Lingual schwannomas generally present as a painless lump with an
      average size of 2 cm in the fourth decade of life and with no gender
      predilection. Complete transoral excision can be considered standard treatment
      for these tumours, with no recurrences documented in the literature. 

PMID- 23853408
TI  - Modern rhinoplasty.

PMID- 23853409
TI  - The role of septal surgery in cosmetic rhinoplasty.
AB  - Septoplasty is performed to resolve breathing problems, but it often becomes
      pivotal to correct external nasal deviation, representing a central step in
      rhinoplasty surgery. Even in patients with no functional problems, septal surgery
      may represent the best solution for obtaining a proper realignment of the
      external nasal pyramid. One-stage septorhinoplasty has become the standard of
      treatment for a deviated nose, hence septoplasty cannot be considered as a
      separate procedure to perform before or after rhinoplasty or as a partial
      operation subject to later revision. The aim of this article is to discuss the
      close relationship between the nasal septum and the aesthetics of the nose, and
      how a graduated surgical approach for the correction of septal deviations could
      affect the external deviated nose. 

PMID- 23853410
TI  - Hybrid rhinoplasty: beyond the dichotomy of rhinoplasty techniques.
AB  - Although rhinoplasty and the development of facial aesthetic criteria can be
      traced to several millennia, contemporary techniques have passed through a rapid
      evolutionary process in the past century (1) (2). Although understanding human
      anatomy and the consequences of surgical excision occupied the minds of the
      founders of rhinoplasty, the process moved towards preservation of supporting
      structures, and maintaining the physiological functions of the nose. Initially,
      this endonasal approach created its own series of problems due to excessive
      tissue removal. External rhinoplasty provided a new impetus for growth in this
      field, and since its inception, has swung the pendulum of reconstruction firmly
      into its own sphere of influence. However, as no rhinoplasty technique holds all
      the answers, hybrid rhinoplasty seeks to combine the best achievements of 20(th)
      century rhinoplasty, from all schools of thought, in order to provide a safe,
      sensible and planned approach to the most demanding operation for the facial
      plastic surgeon. 

PMID- 23853411
TI  - The crooked nose.
AB  - The crooked nose is unquestionably the most severe deformity of the nasal septum
      due to the simultaneous involvement of very important functional and aesthetic
      elements. As everyday interpersonal relations are primarily conducted face-to
      face, deviation of the nasal pyramid from the median line is immediately obvious
      even to the least observant. The surgical procedures used to address this
      pathology must take into account the risk of relapse due to the elastic "memory"
      of the cartilage and avoid any undue weakening of the structure resulting in
      collapse of the nasal dorsum. The complexity of the problem requires techniques
      capable of addressing the situation radically and providing results that are
      stable over time. Extracorporeal septoplasty, spreader grafts and the crossbar
      graft are all particularly effective, not only in correcting deformity of the
      nasal pyramid but also in solving functional respiratory problems. The author
      describes the techniques in detail and discusses their strengths with respect to
      specific problems of the crooked nose. 

PMID- 23853412
TI  - Grafts in "closed" rhinoplasty.
AB  - Rhinoplasty is a fascinating and complex surgical procedure aiming at attaining a
      well-functioning and aesthetically pleasant nose. The use of grafts is of the
      utmost importance for the nasal surgeon to achieve such results. However, the
      philosophy and technical use of nasal grafts are different in "closed" and "open"
      rhinoplasty. The aim of this paper is not detailed description of the numerous
      grafts reported in the literature; we will describe the main principles of grafts
      use in "closed" rhinoplasty derived from our experience, with special reference
      to the philosophical and technical differences in their employment between
      "closed" and "open" rhinoplasty. Some cases are reported as an example of graft
      use in "endonasal" approach rhinoplasty. 

PMID- 23853413
TI  - Surgical correction of "rhinoplastic look".
AB  - A pointed, narrow and exaggeratedly upturned nasal tip and concave dorsal profile
      can give the nose an unnatural and artificial appearance that is the unmistakable
      hallmark of plastic surgery. As a result of changes in social attitudes, noses
      that have evidently been operated on are no longer acceptable and requests are
      made for correction. While a more natural dorsal profile can be obtained with
      camouflage grafts of autologous cartilage or alloplastic material (EPTFE),
      autologous grafts alone are used to reconstruct the tip. The most complex
      correction regards an obtuse nasolabial angle, for which the extension graft
      technique is used. Particular care must be taken during preoperative planning,
      where the aid of computer simulation and agreement with the patient are
      essential. 

PMID- 23853414
TI  - Grafting in revision rhinoplasty.
AB  - Rhinoplasty is one of the most difficult aesthetic surgery procedures with a high
      rate of revision. In revision rhinoplasty the surgeon should explore the
      patient's concerns and then verify the possibility to satisfy expectations after
      complete internal and external examination of the nose. For the vast majority of
      complex secondaries, an open approach is the only reasonable method. In fact, in
      secondary nasal surgery, because of the scarring process following the primary
      operation, dissection is tedious, and landmarks are lost. One of the main
      objectives for the surgeon who approaches secondary rhinoplasty is to restore the
      structural support of the nose and to replace the lost volume of soft tissues. To
      achieve this purpose, the surgeon must often rely on grafts. An ideal grafting
      material must be easy to sculpt, resistant to trauma, infection and extrusion,
      mechanically stable, inert and readily available. For all these reasons,
      autogenous cartilage grafts harvested from septum, auricular concha and rib
      represent the first choice in rhinoplasty. In order to obtain a camouflage graft
      that provides natural contouring to the nose, temporalis fascia can be used. All
      these carefully trimmed grafts are useful in tip revision surgery, in secondary
      surgery of the dorsum and to resolve or reduce functional problems. 

PMID- 23853415
TI  - Rib grafts in septorhinoplasty.
AB  - Autogenous cartilage has generally been considered the gold standard grafting
      material in reconstructive septorhinoplasty for volume filling and structural
      support. In the restructuring of the nasal skeleton, autogenous cartilage can be
      harvested from the nasal septum, the auricle or the rib, but costal cartilage is
      considered the best graft material in patients requiring major reconstruction.
      Rib cartilage is an outstanding material in reconstructive septorhinoplasty,
      especially in revision surgery and when large amounts of tissue are required.
      This autologous material has a low rate of complications such as resorption,
      infection and extrusion compared to homografts and alloplastic implants. In the
      present study, the authors analyze and discuss the use of autogenous rib
      cartilage in 54 patients who underwent primary and revision septorhinoplasty. Its
      use is also suggested in cases in which there is a need to have a fair amount of
      cartilaginous tissue to be grafted for nasal framework reconstruction and
      respiratory function improvement. 

PMID- 23853416
TI  - Nasal valve surgery.
AB  - The nasal valve region plays a key role in nasal breathing. In the international
      literature, a variety of techniques have been described to rectify nasal valve
      compromise, but based on the present evidence it is impossible to counsel a
      patient as to which technique is most effective. The aim of this study was to
      evaluate the results of surgery of the nasal valve through a hemitransfixion
      incision objectively with nasal endoscopy and rhinomanometry. The study group
      consisted of 54 males and 15 females with a mean age of 41.8 +/- 14.4 years,
      (range: 21-72 years). After a mean follow-up of 8 +/- 4.1 months, nasal endoscopy
      demonstrated the favourable effects of surgical treatment with a normalization of
      the nasal valve angles. Only 5 patients showed persistent nasal valve stenosis,
      and were scheduled for revision surgery. Preoperatively, total decongested
      inspiratory NARs were 0.245 +/- 0.091 Pa/cm3/s and decreased significantly after
      the operation (p < 0.0005) to 0.154 +/- 0.059 Pa/cm3/s. Similarly, preoperatively
      total decongested expiratory NARs were 0.188 +/- 0.068 Pa/cm3/s and decreased
      significantly after the operation (p < 0.0005) to 0.142 +/- 0.059 Pa/cm3/s.
      Moreover, total dilated inspiratory and expiratory NARs resulted significantly (p
      < 0.0005) lower than the preoperatively total decongested NARs, with a mean value
      of 0.120 +/- 0.059 Pa/cm3/s and 0.102 +/- 0.057 Pa/cm3/s, respectively.
      Statistical analysis did not reveal any influence of sex and age in
      rhinomanometric measurements. Hemitransfixion incision allowed a wide access to
      the whole valve area for inspection and correction of the various components.
      Rhinomanometry, performed in a decongested condition and after dilation test, was
      thus a useful diagnostic tool for the preoperative diagnosis of nasal valve
      obstruction and permitted to assess quantitatively the favourable effect of
      surgical procedures. 

PMID- 23853418
TI  - Comparison of screening methods for high-throughput determination of oil yields
      in micro-algal biofuel strains.
AB  - The phenotypic and phylogenetic diversity of micro-algae capable of accumulating
      triacylglycerols provides a challenge for the accurate determination of
      biotechnological potential. High-yielding strains are needed to improve economic
      viability and their compositional information is required for optimizing
      biodiesel properties. To facilitate a high-throughput screening programme, a very
      rapid direct-derivatization procedure capable of extracting lyophilized material
      for GC analysis was compared with a scaled-down Folch-based method. This was
      carried out on ten micro-algal strains from 6 phyla where the more rapid direct
      derivatization approach was found to provide a more reliable measure of yield.
      The modified Folch-based procedure was found to substantially underestimate oil
      yield in one Chlorella species (P < 0.01). In terms of fatty acid composition
      however, the Folch procedure proved to be slightly better in recovering
      polyunsaturated fatty acids, in six out of the ten strains. Therefore, direct
      derivatization is recommended for rapid determination of yields in screening
      approaches but can provide slightly less compositional accuracy than solvent
      based extraction methods.

PMID- 23853419
TI  - Persisters and nonpersisters: Identifying the characteristics of who stays and
      who leaves from adult literacy interventions.
AB  - Adult literacy programs are characterized by high attrition rates. Rigorous
      exploration of student persistence in adult reading classes is lacking. This
      study was an attempt to understand the profiles of adults who completed reading
      classes compared to a group of adults who made it to the midpoint and a group of
      adults who did not make it to the midpoint. Students were offered 100 hours of
      instruction. Of the 395 students who attended the first day of class, only 198
      completed the program. Results indicated that English language status, age, some
      reading related skills, class assignment, avoidance of reading, previous adult
      education experience, and Women, Infants, and Children (WIC) benefit receipt
      variables significantly predicted persistence. The significance of some of these
      predictors varied based on analyzing midpoint completion or full completion. To
      further explore the characteristics of the sample, the most representative
      participants were selected from the group that did not make it to midpoint and
      from the group that completed the program. Results indicated that the most
      representative members of these two groups differed in English language status,
      gender, age, some reading related skills, and information access.

PMID- 23853417
TI  - Innovative technique for large septal perforation repair and radiological
      evaluation.
AB  - PERFORATION OF THE NASAL SEPTUM MAY HAVE MULTIPLE CAUSES: traumatic, iatrogenic,
      infectious, degenerative, overuse of vasoconstrictors, abuse of cocaine and more
      recently chemotherapy agents. Perforations are also classified according to their
      size and type of cartilaginous or osteocartilaginous deficit, as well as location
      (front, middle and rear). Many surgical techniques have been proposed to repair
      the perforation, although the results are often unsatisfactory for perforations
      of small and medium size; in large perforations permanent obliteration of the
      defect cannot always be ensured. It is often necessary to use tissues from inside
      the nasal turbinates or cartilage from other donor sites such as the ear or rib,
      and various techniques are discussed in light of the recent literature. The
      perforations observed in the last eight years and surgical approaches performed
      in open or closed approaches are taken into account. The authors propose a new
      technique that has been used with success in many types of septal perforation
      regardless of aetiology, and in particular large perforations, which allows for
      the use of the osteocartilaginous donor site as a hump. It is also useful in
      reductive rhinoseptoplasty, which targets selection to easily obtain
      mucopericondral flaps with an extramucosal technique and to obtain also an
      aesthetic improvement.

PMID- 23853421
TI  - Applications of anthropometry in torsoplastic surgery.
AB  - The study of anthropometry defines the beauty of the torso from a geometric
      perspective. Anthropometry therefore aids the plastic surgeon in planning the
      reshaping of the torso and also makes positioning of areolae and the umbilicus
      easier. When performing surgery on the breast, it is necessary to relate the
      breast to the torso as a whole, being anthropometry perfect for this process.
      When the anthropometric proportions are respected, the result is aesthetically
      optimal, and the perceived beauty of the body is enhanced. The study of
      anthropometry is widespread in the artistic field, and I have chosen the work of
      sculptor, Carlo Rochet, as the basis for my own use of anthropometry during
      plastic surgery. Level of Evidence: Level V, diagnostic study.

PMID- 23853420
TI  - Modeling the relationships between cognitive-linguistic skills and writing in
      Chinese among elementary grades students.
AB  - The present study is a four-year longitudinal study examining the important
      predictors of writing of 340 Chinese children in elementary grades. Children's
      transcription skills (handwriting skills and spelling), and syntactic skills in
      grade 1 were significant predictors of text writing in grade 1-4 while ideation
      in grade 1 only contributed to text writing in grade 2. Stroke order knowledge
      was shown as an important handwriting skill in Chinese reflecting the
      characteristics of the Chinese orthography. A model of Chinese writing in early
      elementary grades was proposed. In the model, orthographic knowledge,
      morphological awareness and handwriting skills are proposed to contribute to
      spelling which is correlated with text writing. Handwriting skills, ideation, and
      syntactic skills were found to contribute to text writing. Path analysis results
      suggest that the longitudinal relationship between spelling and text writing is
      bidirectional.

PMID- 23853422
TI  - Impact of SOD-Mimetic Manganoporphyrins on Spin Trapping of Superoxide and
      Related Artifacts.
AB  - The superoxide dismutase (SOD)-mimetic effectiveness of [meso-tetrakis
      (R)porphyrinato]manganese with R = 1,3-di-N-ethylimidazolium-2-yl (Mn-TDEIP), 1,3
      di-N-methylimidazolium-2-yl (Mn-TDMIP), 1,3-di-N-propylimidazolium-2-yl (Mn
      TDPIP), N-ethyl-2-pyridyl (Mn-T2EPyP), 4-sulphonatophenyl (Mn-TSP), 1-methyl-4
      pyridyl (Mn-T4PyP), 4-carboxyphenyl (Mn-TBAP), and beta-octabromomeso-tetrakis(4
      carboxyphenyl porphyrinato)manganese (MnBr8TBAP) was compared with Cu, Zn SOD.
      Superoxide generated by reaction of xanthine oxidase with hypoxanthine was
      trapped with 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), forming
      BMPO-OOH, which was monitored by electron paramagnetic resonance.
      Manganoporphyrins with redox potentials ranging from -0.190 to 0.346 V relative
      to the standard hydrogen electrode were selected for this study. With 0.1 uM
      manganoporphyrins and 20 mM BMPO, the effectiveness of the manganoporphyrins in
      inhibiting formation of BMPO-OOH increases in the order Mn-TSP < Mn-TBAP <
      MnBr8TBAP < Mn-T4PyP < Mn-T2EPyP < Mn-TDEIP ~ Mn-TDMIP ~ Mn-TDPIP ~ Cu, Zn SOD.
      However, at higher concentrations of manganoporphyrin and BMPO, a BMPO-OH signal
      was observed. The formation of BMPO-OH was not inhibited by catalase or
      dimethylsulfoxide, which demonstrated that it was not produced from hydroxyl
      radical. The artifactual formation of BMPO-OH is attributed to oxidation of the
      water adduct of BMPO by the manganoporphyrins or decomposition of BMPO-OOH.
      Although spin trapping is an effective method for evaluating SOD-mimetic
      efficacy, caution must be exercised to ensure that artifact signals are not
      interpreted improperly.

PMID- 23853423
TI  - Yukawa-Field Approximation of Electrostatic Free Energy and Dielectric Boundary
      Force.
AB  - A Yukawa-field approximation of the electrostatic free energy of a molecular
      solvation system with an implicit or continuum solvent is constructed. It is
      argued through the analysis of model molecular systems with spherically symmetric
      geometries that such an approximation is rational. The construction extends non
      trivially that of the Coulomb-field approximation which serves as a basis of the
      widely used generalized Born model of molecular electrostatics. The electrostatic
      free energy determines the dielectric boundary force that in turn influences
      crucially the molecular conformation, stability, and dynamics. An explicit
      formula of such forces with the Yukawa-field approximation is obtained using
      local coordinates and shape differentiation.

PMID- 23853424
TI  - Chemical defense of an Asian snake reflects local availability of toxic prey and
      hatchling diet.
AB  - Species that sequester toxins from prey for their own defense against predators
      may exhibit population-level variation in their chemical arsenal that reflects
      the availability of chemically defended prey in their habitat. Rhabdophis
      tigrinus is an Asian snake that possesses defensive glands in the skin of its
      neck ('nuchal glands'), which typically contain toxic bufadienolide steroids that
      the snakes sequester from consumed toads. In this study, we compared the
      chemistry of the nuchal gland fluid of R. tigrinus from toad-rich and toad-free
      islands in Japan and determined the effect of diet on the nuchal gland
      constituents. Our findings demonstrate that captive-hatched juveniles from toad
      rich Ishima Island that had not been fed toads possess defensive bufadienolides
      in their nuchal glands, presumably due to maternal provisioning of these
      sequestered compounds. Wild-caught juveniles from Ishima possess large quantities
      of bufadienolides, which could result from a combination of maternal provisioning
      and sequestration of these defensive compounds from consumed toads.
      Interestingly, juvenile females from Ishima possess larger quantities of
      bufadienolides than do juvenile males, whereas a small sample of field-collected
      snakes suggests that adult males contain larger quantities of bufadienolides than
      do adult females. Captive-born hatchlings from Kinkasan Island lack
      bufadienolides in their nuchal glands, reflecting the absence of toads on that
      island, but they can sequester bufadienolides by feeding on toads (Bufo
      japonicus) in captivity. The presence of large quantities of bufadienolides in
      the nuchal glands of R. tigrinus from Ishima may reduce the risk of predation by
      providing an effective chemical defense, whereas snakes on Kinkasan may
      experience increased predation due to the lack of defensive compounds in their
      nuchal glands.

PMID- 23853425
TI  - A wavelet multiscale denoising algorithm for magnetic resonance (MR) images.
AB  - Based on the Radon transform, a wavelet multiscale denoising method is proposed
      for MR images. The approach explicitly accounts for the Rician nature of MR data.
      Based on noise statistics we apply the Radon transform to the original MR images
      and use the Gaussian noise model to process the MR sinogram image. A translation
      invariant wavelet transform is employed to decompose the MR 'sinogram' into
      multiscales in order to effectively denoise the images. Based on the nature of
      Rician noise we estimate noise variance in different scales. For the final
      denoised sinogram we apply the inverse Radon transform in order to reconstruct
      the original MR images. Phantom, simulation brain MR images, and human brain MR
      images were used to validate our method. The experiment results show the
      superiority of the proposed scheme over the traditional methods. Our method can
      reduce Rician noise while preserving the key image details and features. The
      wavelet denoising method can have wide applications in MRI as well as other
      imaging modalities.

PMID- 23853426
TI  - Oxygen Releasing Biomaterials for Tissue Engineering.
AB  - Due to the increasing demand to generate thick and vascularized tissue engineered
      constructs, novel strategies are currently being developed. An emerging example
      is the generation of oxygen-releasing biomaterials to tackle mass transport and
      diffusion limitations within engineered tissue-like constructs. Biomaterials
      containing oxygen releasing molecules can be fabricated in various forms such as,
      hybrid thin films, microparticles, or three dimensional (3D) scaffolds. In this
      perspective, we will summarize various oxygen-releasing reagents and their
      potential applications in regenerative engineering. Moreover, we will review the
      main approaches to fabricate oxygen-releasing biomaterials for a range of tissue
      engineering applications.

PMID- 23853429
TI  - State of the globe: antimicrobial stewardship guides rationale use of
      antimicrobials to enable faster cure and prevent drug resistance.

PMID- 23853428
TI  - MMP-3 contributes to nigrostriatal dopaminergic neuronal loss, BBB damage, and
      neuroinflammation in an MPTP mouse model of Parkinson's disease.
AB  - The present study examined whether matrix metalloproteinase-3 (MMP-3)
      participates in the loss of dopaminergic (DA) neurons in the nigrostriatal
      pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of
      Parkinson's disease with blood brain barrier (BBB) damage and infiltration of
      peripheral immune cells. Tyrosine hydroxylase (TH) immunostaining of brain
      sections from MPTP-treated mice showed that MPTP induced significant degeneration
      of nigrostriatal DA neurons. Moreover, FITC-labeled albumin detection and
      immunostaining revealed that MPTP caused damage to the BBB and increased the
      number of ED-1- and CD-3-immunopositive cells in the substantia nigra (SN).
      Genetic ablation of MMP-3 reduced the nigrostriatal DA neuron loss and improved
      motor function. This neuroprotective effect afforded by MMP-3 deletion was
      associated with the suppression of BBB disruption and a decrease in the number of
      ED-1- and CD-3-immunopositive cells in the SN. These data suggest that MMP-3
      could play a crucial role in neurodegenerative diseases such as PD in which BBB
      damage and neuroinflammation are implicated. 

PMID- 23853430
TI  - The pattern and impact of infectious diseases consultation on antimicrobial
      prescription.
AB  - OBJECTIVES: Inclusion of infectious disease (ID) physicians in the care of
      patients with possible infection can favorably affect antibiotic usage. The aim
      of this study was to evaluate the role of the ID consultations in reducing
      inappropriate antibiotic usage. MATERIALS AND METHODS: This is a prospective
      study evaluating all adult ID consultations from January 2006 to December 2009. A
      total of 1444 consultation requests were recorded during the 4-year period.
      RESULTS: The most frequent consultations were from cardiology (23.1%),
      orthopedics (8.2%), general medicine (7.8%), hematology-oncology (7.8%),
      gastroenterology (7.3%), and pulmonary/critical care (7.1%). The main reason for
      consultation was for the choice of antibiotics (75%). The commonest diagnoses
      prior to consultation were fever (14.7%), bacteremia (9.1%), and urinary tract
      infection (8.4%). Bacteremia was documented in 21.4% of cases and 12.9% were
      found to have no identifiable focus of infection. Antimicrobial therapy was
      changed in 58.7% and antimicrobials were discontinued in 14.7% of cases. The
      number of antimicrobial therapy was one (49.7% and 49.9%) and two (24% and 17.6%,
      P = 0.0001) before and after the consultation, respectively. In addition, 17.3%
      and 26.9% (P = 0.0001) received no antimicrobial agents before and after ID
      consultation. CONCLUSION: ID consultation is important to reduce inappropriate
      antimicrobial therapy and to limit the number of dual therapy.

PMID- 23853431
TI  - Multiplex PCR for rapid diagnosis of gastrointestinal tuberculosis.
AB  - BACKGROUND: Rapid and specific diagnosis of gastrointestinal tuberculosis (GITB)
      is of utmost importance. AIM: To evaluate Multiplex PCR (MPCR) using MPB64 and
      IS6110 primers specific for M. tuberculosis for rapid diagnosis of GITB.
      MATERIALS AND METHODS: MPCR was performed on colonoscopy biopsy specimens on 11
      GITB confirmed (culture/AFB/histopathology was positive), 29 GITB suspected and
      30 Non GITB (control group) patients. RESULTS: MPB64 PCR had sensitivity and
      specificity of 90% and 100% for confirmed GITB cases. In 29 clinically diagnosed
      but unconfirmed GITB cases, MPCR was positive in 72.41%. MPCR was negative in all
      control group patients. The overall sensitivity and specificity of microscopy,
      culture, histopathology and MPCR was 5%, 2% 20% and 77.5% and 100%, 100%, 100%
      and 100% respectively. CONCLUSION: MPCR has good sensitivity and specificity in
      diagnosing gastrointestinal tuberculosis.

PMID- 23853427
TI  - Cytokines in sepsis: potent immunoregulators and potential therapeutic targets-
      an updated view.
AB  - Sepsis and septic shock are among the leading causes of death in intensive care
      units worldwide. Numerous studies on their pathophysiology have revealed an
      imbalance in the inflammatory network leading to tissue damage, organ failure,
      and ultimately, death. Cytokines are important pleiotropic regulators of the
      immune response, which have a crucial role in the complex pathophysiology
      underlying sepsis. They have both pro- and anti-inflammatory functions and are
      capable of coordinating effective defense mechanisms against invading pathogens.
      On the other hand, cytokines may dysregulate the immune response and promote
      tissue-damaging inflammation. In this review, we address the current knowledge of
      the actions of pro- and anti-inflammatory cytokines in sepsis pathophysiology as
      well as how these cytokines and other important immunomodulating agents may be
      therapeutically targeted to improve the clinical outcome of sepsis. 

PMID- 23853432
TI  - Mapping the pattern and trends of extrapulmonary tuberculosis.
AB  - BACKGROUND AND OBJECTIVES: There has been a rapid expansion of the directly
      observed treatment short-term (DOTS) under the revised national tuberculosis
      control program throughout India in the last decade. Few reports exist detailing
      individual DOTS centers' experiences with regard to extrapulmonary tuberculosis
      (EPTB) in a medical college hospital setting. MATERIALS AND METHODS: This is a
      retrospective, record-based study of patients with the diagnosis of EPTB, in all
      age groups. Data on all consecutive EPTB cases diagnosed at the K. S. Hegde
      Medical College and Hospital, Deralakatte, Mangalore from 1 January 2005 to 31
      December 2011 at the DOTS centre attached to this hospital were collected,
      analyzed by Mantel-Haenszel Chi square for linear trend and described in
      proportion or percentages. RESULTS: Among 1267 cases registered for treatment of
      all forms of tuberculosis, 528 (41.67%) had EPTB. Around half of the cases of
      EPTB (269, 51%) were among adult age groups and the majority of cases (342,
      64.77%) received Category-I treatment. Pleural TB was the commonest type of EPTB
      (n = 148, 28.03%), followed by lymph node TB (n = 131, 24.81%). Involvement of
      lymph nodes was the commonest manifestation among the less than 14 years' age
      group (27, 58.7%), while involvement of pleura was more common among > 65 years'
      age group (23, 45.1%). The difference in the occurrence of EPTB by site between
      males and females is statistically significant with a P value of <0.005. There is
      a significant increase in the number of cases of tuberculosis affecting bones and
      joints, and other forms of tuberculosis over the years. CONCLUSION: The burden of
      EPTB is more among the productive age group. Increase in the trend of bone and
      joint tuberculosis, and other rare forms of EPTB is a point of concern
      highlighting the importance of strengthening the services towards this group.

PMID- 23853433
TI  - Assessment of risk factors of helicobacter pylori infection and peptic ulcer
      disease.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) infection is a risk factor for peptic
      ulcer. There have been no studies addressing environmental and dietary risk
      factors in western India. We conducted a case control study enrolling peptic
      ulcer patients in Pune, India. MATERIALS AND METHODS: Risk factors for peptic
      ulcer and H. pylori infection were assessed in a participant interview. H. pylori
      status was assessed from stool by monoclonal antigen detection. RESULTS: We
      enrolled 190 peptic ulcer, 35 stomach cancer patients, and 125 controls. Fifty
      one percent (180/350) of the participants were infected with H. pylori. Lower
      socioeconomic status (SES) [odds ratio (OR): 1.10, 95% confidence interval (CI):
      1.02-1.39], meat consumption (OR: 2.35, 95% CI: 1.30-4.23), smoking (OR: 2.23,
      95% CI: 1.24-4.02), eating restaurant food (OR: 3.77, 95% CI: 1.39-10.23), and
      drinking nonfiltered or nonboiled water (OR: 1.05, 95% CI: 1.01-1.23) were risk
      factors for H. pylori infection. H. pylori infection (OR: 1.70, 95% CI: 1.03
      2.89), meat (OR: 1.10, 95% CI: 1.02-1.75), fish (OR: 1.05, 95% CI: 1.02-1.89)
      consumption, and a family history of ulcer (OR: 1.20, 95% CI: 1.08-1.60) were
      risk factors for peptic ulcer. Consumption of chili peppers (OR: 0.20, 95% CI:
      0.10-0.37) and parasite infestation (OR: 0.44, 95% CI: 0.24-0.80) were protective
      against H. pylori infection. CONCLUSION: H. pylori infection is associated with
      peptic ulcer. Lower SES, consumption of restaurant food, meat, nonfiltered water,
      and smoking are risk factors for H. pylori. Consumption of meat, fish, and a
      family history of peptic ulcer are risk factors for peptic ulcer. Consumption of
      chili peppers and concurrent parasite infestation appear to be protective against
      H. pylori.

PMID- 23853434
TI  - Detection of invasive aspergillosis in bone marrow transplant recipients using
      real-time PCR.
AB  - OBJECTIVE: The invasive aspergillosis (IA) is a serious opportunistic infection
      caused by various species of Aspergillus in immunocompromised individuals.
      Basically, rapid and early diagnosis prevents IA progression. In this study we
      performed a Real Time PCR/ Fluorescence Resonance Energy Transfer (FRET) for
      diagnosis of IA in hematologic malignancies and bone marrow transplant
      recipients. MATERIALS AND METHODS: Sixty two patients with hematologic
      malignancies and marrow transplant recipients were evaluated for IA in Sari and
      Tehran from 2009 to 2010. The primer and hybridization probe were designed to
      amplify the specific sequence of 18S rRNA genes using Light Cycler system and
      FRET. Galactomannan (GM) assay was performed on serums which obtained from
      selected patients using the Platelia Aspergillus kit. RESULTS: According to the
      criteria defined by the European Organization for Research and Treatment of
      Cancer and Mycoses Study Group (EORTC/MSG) for IA, 18 (29%) patients out of 62
      patients were stratified into probable and possible groups. The female-to-male
      ratio was 1:2; the mean age of the patients was 36 years. The most common
      malignancies in these patients were acute lymphoblastic leukemia (38.9%). The
      minimum detection limit was 10 conidia (10(1) CFU/ml) equivalents (100 fg) per
      PCR reaction. GM assay was positive in 20.9% and real-time PCR probe set assay
      were positive in 17.7% patients who had clinical signs and host factor according
      to the mentioned criteria. CONCLUSION: Using the Real-Time PCR/FRET assay in
      whole blood specimens seems to be a promising method for diagnosis of IA,
      especially when used in combination with the GM detection test.

PMID- 23853435
TI  - Data from the World Health Organization (WHO) National Network Laboratory for
      Japanese Encephalitis.
AB  - AIM: Japanese encephalitis (JE) virus is the leading cause of viral neurologic
      disease and disability in Asia. In the present study JE virus-specific IgM in
      serum and CSF from acute encephalitis syndrome (AES) patients, attending Assam
      Medical College and Hospital (AMC and H), Dibrugarh, Assam from 2007 to 2009 were
      detected and different epidemiological parameters namely age, season and
      vaccination campaign were enumerated. MATERIALS AND METHODS: A cross-sectional
      study on patients with AES admitted in AMC and H, Dibrugarh, Assam was done
      during 2007 to 2009. The different epidemiological features were characterized
      depending on a pretested structured questionnaire called the clinical information
      form (CIF). Serum and CSF obtained were tested by a Panbio JE-Dengue IgM Combo
      ELISA kit and JEV Chex kit (Xycton). STATISTICAL ANALYSIS: A z-test was used for
      the statistical analytic assessment. RESULTS: Detection rate of JE was 39.4%,
      51.1%, and 51.3% in the years 2007, 2008, and 2009 respectively. Cases of JE
      increased in the age group more than 15 years in the district where the
      vaccination program was undertaken. This increase of cases from pediatric to
      adults is also statistically significant by the z-test (P<0.05). CONCLUSION:
      There was an increase in AES cases and also JE cases from 2007 to 2009. JE also
      showed a seasonal variation with maximum cases in the months of July and August.
      Although vaccination campaigns with the live attenuated vaccine SA-14-14-2 have
      started and are protecting the under-15 children, there is a shift of disease
      pattern in the older population.

PMID- 23853436
TI  - Salmonella typhi rib osteomyelitis with abscess mimicking a 'cold abscess'.
AB  - Salmonella enterica serovar typhi (Salmonella typhi) causing typhoid fever is
      common in many parts of the world particularly in developing countries. Extra
      intestinal manifestations such as osteomyelitis are rare in immunocompetent
      individuals. We report a case of Salmonella typhi osteomyelitis of a rib with
      overlying abscess mimicking a 'cold abscess', treatment outcomes and discuss
      relevant literature. 

PMID- 23853437
TI  - Community-Acquired urinary tract infection by pseudomonas oryzihabitans.
AB  - Pseudomonas oryzihabitans and Chrysomonas luteola has been placed in CDC group
      Ve2 and Ve1 respectively. These bacteria appear to be emerging pathogens. P.
      oryzihabitans was isolated from cases of bacteremia, CNS infections, wound
      infections, peritonitis, sinusitis, catheter associated infections in AIDS
      patient, and pneumonia. Most of the reports of P. oryzihabitans infection were of
      nosocomial origin in individuals with some predisposing factors. We report here a
      case of community acquired UTI by P. oryzihabitans in an immune-competent patient
      with stricture of urethra. 

PMID- 23853438
TI  - Nontuberculous mycobacterial arthritis of the first metatarsophalangeal joint in
      a young immunocompetent adult: an interesting case report.

PMID- 23853439
TI  - Diagnosis of extrapulmonary tuberculosis by polymerase chain reaction for mpb64
      gene: an evaluation in a hospital based study.

PMID- 23853440
TI  - Seropositivity for brucellosis in veterinarians.

PMID- 23853441
TI  - Intractable Hiccups in an Elderly Diabetic: An Unusual Presentation of Ascaris
      lumbricoides.

PMID- 23853442
TI  - Not All Vaccines are Cost-beneficial in Developing Countries.

PMID- 23853443
TI  - Drug dependence: Cancer medicine.

PMID- 23853444
TI  - Comparison of soft-tissue, dental, and skeletal characteristics in children with
      and without tongue thrusting habit.
AB  - BACKGROUND: Tongue thrusting habit is a condition in which the tongue makes
      contact with any teeth anterior to the molars during swallowing. Abnormal
      positioning of tongue may result in dental and skeletal abnormalities. OBJECTIVE:
      The aim of the present study was to study and compare soft-tissue, dental, and
      skeletal morphologic characteristics in children with and without tongue
      thrusting habit. MATERIALS AND METHODS: A total of 21 children with tongue
      thrusting habit and 21 children without any habit between age 10 and 14 years
      were selected for the study. Various soft-issue, dental and cephalometric
      parameters were measured and compared statistically. RESULTS: Significantly,
      higher number of children with tongue thrusting showed lip incompetency (86% vs.
      14%), mouth-breathing habit (38% vs. none), hyperactive mentalis muscle activity
      (24% vs. none), Open-bite (52% vs. none) and lisping (86% vs. none) when compared
      to children without tongue thrust. Children with tongue thrust showed increased
      upper lip thickness and proclination of maxillary incisors No differences were
      found in angulation of mandibular incisors, inter-premolar or inter-molar widths
      and all the skeletal parameters studied. CONCLUSIONS: Tongue thrust seemed to
      affect some of the soft-tissue and dental characteristics causing lip
      incompetency, mouth-breathing habit, and hyperactive mentalis muscle activity,
      lisping, open-bite, and proclination of maxillary incisors; however, no
      significant skeletal changes were observed.

PMID- 23853445
TI  - Suprabasal expression of Ki-67 as a marker for the severity of oral epithelial
      dysplasia and oral squamous cell carcinoma.
AB  - BACKGROUND: Transition of the normal oral epithelium to dysplasia and to
      malignancy is featured by increased cell proliferation. To evaluate the
      hypothesis of distributional disturbances in proliferating and stem cells in oral
      epithelial dysplasia and oral squamous cell carcinoma (OSCC). AIM: To evaluate
      layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC.
      MATERIALS AND METHODS: Thirty histologically confirmed cases of oral epithelial
      dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were
      immunohistochemically examined and nuclear expression of Ki-67 was counted
      according to basal, parabasal, and suprabasal layers in epithelial dysplasia and
      number of positive cells per 100 cells in OSCC as labeling index (LI). RESULTS:
      Suprabasal expression of Ki-67 increased according to the severity of epithelial
      dysplasia and the difference was statistically significant (P < 0.001). The mean
      Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for
      OSCC and 13.6 for normal buccal mucosa. CONCLUSION: The results of the present
      study demonstrate the use of proliferative marker Ki-67 in assessing the severity
      of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective
      criteria for determining the severity of epithelial dysplasia and histological
      grading of OSCC.

PMID- 23853446
TI  - The use of bone block allografts in sinus augmentation, followed by delayed
      implant placement: A case series.
AB  - PURPOSE: This article reports the clinical outcomes observed in a large number of
      patients receiving block bone allograft used for sinus augmentation and delayed
      implant placement. PATIENTS AND METHODS: In total, 28 patients (13 males) with a
      mean age of 49.8 +/- 10.1 years (range: 33-67 years) were included in this case
      series. All selected patients suffered from severe alveolar ridge atrophy in the
      posterior maxilla and required bone augmentation procedures, followed by implant
      placement after 6 months. All patients were followed for 18 months after the
      grafting, with scheduled monthly visits and/or more frequent visits if required.
      The survival rates for both the bone blocks and placed implants were then
      evaluated. RESULTS: A total of 42 blocks and 90 implants were placed. Only one
      bone graft and 5 implants failed; the survival rate was 97.2% and 95.5% for the
      bone grafts and implants, respectively. The graft failed due to the onset of post
      surgical infectious sinusitis, while in some patients' implants showed absence of
      osteointegration at the end of the healing phase. Of note, all failed implants
      were observed in heavy smokers; in all other patients, blocks and implants were
      successful. CONCLUSIONS: This preliminary case series suggests that the grafting
      of bone allograft followed by delayed implant placement may be a promising
      strategy for sinus augmentation. More extended and larger follow-up studies are
      needed to confirm this preliminary data.

PMID- 23853447
TI  - Shear bond strength and SEM morphology evaluation of different dental adhesives
      to enamel prepared with ER:YAG laser.
AB  - CONTEXT: Early observations of enamel surfaces prepared by erbium lasers
      motivated clinicians to use laser as an alternative to chemical etching. AIMS:
      Evaluate shear bond strength (SBS) values of different dental adhesives on
      Erbium:Yttrium Aluminum Garnet (Er:YAG) laser prepared enamel and to evaluate
      possible etching patterns correlations between dental adhesives and SBS values.
      SUBJECTS AND METHODS: One hundred bovine incisors were randomly assigned to SBS
      tests on enamel (n = 15) and to enamel morphology analysis (n = 5) after Er:YAG
      laser preparation as follows: Group I - 37% phosphoric acid (PA)+ ExciTE((r));
      Group II - ExciTE((r)); Group III - AdheSE((r)) self-etching; Group IV -
      FuturaBond((r)) no-rinse. NR; Group V - Xeno((r)) V. Teeth were treated with the
      adhesive systems and subjected to thermal cycling. SBS were performed in a
      universal testing machine at 5 mm/min. STATISTICAL ANALYSIS USED: One-way ANOVA
      and post-hoc tests (P < 0.05). For the morphology evaluation, specimens were
      immersed in Ethylenediamine tetraacetic acid (EDTA) and the etching pattern
      analyzed under Scanning Electron Microscope (SEM). RESULTS: Mean bond strengths
      were Group I - 47.17 +/- 1.61 MPa (type I etching pattern); Group II - 32.56 +/-
      1.64 MPa, Group III - 29.10 +/- 1.34 MPa, Group IV - 23.32 +/- 1.53 MPa (type III
      etching pattern); Group V - 24.43 MPa +/- 1.55 (type II etching pattern).
      CONCLUSIONS: Different adhesive systems yielded significantly different SBSs.
      Acid etching significantly increased the adhesion in laser treated enamel. No
      differences in SBS values were obtained between AdheSE((r)) and ExciTE((r))
      without condition with PA. FuturaBond((r)) NR and Xeno((r)) V showed similar SBS,
      which was lower in comparison to the others adhesives. No correlation between
      enamel surface morphology and SBS values was observed, except when PA was used.

PMID- 23853448
TI  - Protein carbonyl: An oxidative stress marker in gingival crevicular fluid in
      healthy, gingivitis, and chronic periodontitis subjects.
AB  - BACKGROUND: A defined role for reactive oxygen species (ROS) in the tissue
      destruction that characterizes periodontitis has been described. Protein carbonyl
      (PC) is the most widely used biomarker for oxidative damage to proteins, and
      reflects cellular damage induced by multiple forms of ROS. The purpose of this
      study is to determine the presence of PC in gingival crevicular fluid (GCF) in
      healthy, gingivitis, and chronic periodontitis (CP) subjects and to find an
      association, if any. MATERIALS AND METHODS: A total number of 75 subjects (38
      males and 37 females) were selected based on their clinical parameters into three
      groups: Group 1 (25 healthy subjects), Group 2 (25 gingivitis subjects), and
      Group 3 (25 CP subjects). GCF samples were collected to estimate the levels of
      PC. RESULTS: The PC concentration in GCF was highest in subjects with CP as
      compared to gingivitis and healthy subjects and a significant association was
      observed between GCF PC levels and all periodontal parameters. CONCLUSION: There
      was an increase in PC levels in GCF as the disease process progressed from
      healthy to gingivitis and CP, suggesting a role for increased oxidative stress in
      CP.

PMID- 23853449
TI  - Randomized, controlled clinical study to evaluate efficacy of novel indigenously
      designed controlled release flurbiprofen gel system for management of periodontal
      diseases.
AB  - BACKGROUND: This randomized, controlled clinical study was planned to evaluate
      the use of anti-inflammatory drug flurbiprofen in the form of locally delivered
      controlled release gel in the treatment of periodontal disease. MATERIALS AND
      METHODS: The flurbiprofen gel was indigenously prepared in the concentration of
      0.3%. The 30 patients with localized periodontal pockets measuring >=5 mm were
      randomly divided into three groups. The groups received flurbiprofen gel,
      flurbiprofen gel after prophylaxis, and placebo gel after oral prophylaxis,
      respectively. The clinical parameters for plaque and gingival inflammation were
      evaluated at baseline, 7(th) day, and 14(th) day. RESULTS: The results of the
      study suggested the statistically significant (P < 0.05) improvement in the
      gingival status of the patients with the use of flurbiprofen gel as an adjunct to
      scaling and root planing as compared to oral prophylaxis or gel alone.
      CONCLUSION: The data demonstrated that the additional use of local drug delivery
      of flurbiprofen through gel media enhances the positive effects of scaling and
      root planing and helps in faster resolution of the inflammation.

PMID- 23853450
TI  - Comparative evaluation of zinc oxide eugenol versus gelatin sponge soaked in
      plasma rich in growth factor in the treatment of dry socket: An initial study.
AB  - PURPOSE: The aim of this study was to report a comparison between the zinc oxide
      eugenol dressing and plasma rich in growth factor (PRGF) with gelatin sponge in
      the treatment of dry socket. MATERIALS AND METHODS: This study comprised of 45
      patients of dry socket in the span of one year. The patients were randomly
      divided into three groups on the basis of treatments: Group A (PRGF with gelatin
      sponge), group B (zinc oxide eugenol group), and group C (irrigation with sterile
      saline only). The clinical progress was noted at 1(st), 2(nd), 3(rd), 7(th), and
      15(th) day after the treatment. RESULTS: Patient's healing was better in group A
      than in group B but symptomatic pain relief was faster in group B. Group C fared
      worst in both aspects. CONCLUSION: We conclude that PRGF with gelatin sponge
      might be a treatment of choice in the management of dry socket.

PMID- 23853451
TI  - A cross-sectional study of soft tissue facial morphometry in children of West
      Bengal.
AB  - CONTEXT: Facial analysis is the first step in the evaluation of patients with
      orthodontic, cosmetic, or reconstructive procedures of the face, and one of the
      most important components of orthodontic diagnosis and treatment planning. It is
      a well-established fact that human faces differ from one another on the basis of
      race and ethnicity. The study will provide the aesthetic guidelines to assess the
      facial discrepancy in Bengali children to develop a proper treatment plan. AIMS:
      To find out the mean values for selective linear measurements on the facial soft
      tissue of Bengali children, to demonstrate gender differences in the
      measurements. MATERIALS AND METHODS: A cross-sectional study was done on 250
      Bengali children of 6-14 years age, by measuring certain identified facial
      landmarks using a digital caliper. STATISTICAL ANALYSIS USED: Analytical
      statistical method with the help of student's t-test was used to determine mean
      values, standard deviation, and gender differences in the measurements using SPSS
      version 11.0. RESULTS: In 6-8 years age group, male's average inter-endocanthion
      distance was significantly higher than that of females (P < 0.05), whereas in 12
      14 years age group, the same parameter for females was significantly higher than
      that of males (P < 0.001). In 9-11 years age group, the average distance of
      exocanthion to exocanthion was higher for males compared to females, but the
      difference was not significant at 5% level (P > 0.05), though for 87% of cases,
      it was significant (P = 0.13). Total facial height for male subject was
      significantly high compared to that of females (P < 0.001) in 12-14 years age
      group. CONCLUSIONS: The study will provide the aesthetic guidelines to assess the
      facial discrepancy in Bengali children and provide a proper treatment plan
      through a simple and economically reasonable soft tissue analysis method.

PMID- 23853452
TI  - Comparative evaluation of locally delivered minocycline and metronidazole in the
      treatment of periodontitis.
AB  - OBJECTIVE: The aim of this study was to evaluate and compare the efficacy of
      subgingivally delivered Minocycline microspheres and 25% Metronidazole gel when
      used as an adjunct to scaling and root planing (SRP) in the treatment of chronic
      periodontitis. MATERIALS AND METHODS: A randomized, controlled, single center
      study was conducted involving 60 sites in 20 patients suffering from moderate to
      advanced chronic periodontitis. Each patient contributed three sites which were
      randomized to three treatment groups: SRP + insertion of Minocycline microspheres
      at day 1 (Group A), SRP + insertion of Metronidazole gel at day 1 and at day 7
      (Group B), and SRP alone (Group C). Gingival index (GI), plaque index (PI),
      probing pocket depth (PPD), and clinical attachment level (CAL) were recorded at
      day 1, 1 month, and 3 months post therapy. RESULTS: All treatments showed
      significant reductions in PPD and CAL at 1 and 3 months when compared to baseline
      values (P < 0.001). At 3 months, sites treated with minocycline showed an
      additional reduction in PPD of 0.85 +/- 0.03 mm, significantly greater than SRP
      alone. Differences in mean PPD reduction between Group B and Group C and between
      Group A and Group B were not significant. At 3 months, difference in CAL gain
      between Group A and C was 0.50 +/- 0.45, which was statistically significant and
      between Group B and C was 0.35 +/- 0.11, which was not found to be statistically
      significant (P = 0.20). Differences in relative CAL between Group A and Group B
      were also not found to be statistically significant (P = 0.53). CONCLUSION: The
      results concluded that treatment with Minocycline microspheres and Metronidazole
      gel improve PPD and CAL in patients with periodontitis compared to SRP alone.

PMID- 23853453
TI  - Comparative analysis of hyaluronan gel and xanthan-based chlorhexidine gel, as
      adjunct to scaling and root planing with scaling and root planing alone in the
      treatment of chronic periodontitis: A preliminary study.
AB  - AIM: The aim of this study was to evaluate the effects of hyaluronan (HA) and
      chlorhexidine (CHX) gels as adjunct to scaling and root planing (SRP) in the
      treatment of chronic periodontitis. MATERIALS AND METHODS: Sixty patients within
      the age group of 30-65 years recruited to participate in the study were randomly
      equally divided into three groups. Complete SRP and subgingival debridement were
      performed within 6 h in all the patients. For control (Group I) patients, SRP was
      the only treatment modality given; for Group II and III patients, at least 8
      teeth with 4-8 mm probing pocket depth (PPD) were selected for subgingival
      application of HA gel and CHX gel, respectively. Clinical periodontal parameters
      such as gingival index, PPD, and clinical attachment level (CAL) were recorded at
      baseline and 3 months, whereas plaque index was recorded at baseline, 1 month,
      and 3 months. For measuring systemic/hematological parameters, blood samples for
      laboratory tests for total leucocyte count (TLC), differential leucocyte count
      (DLC), and C-reactive protein (CRP) were obtained using standard 2-mL syringe
      from each subject in all the three groups at baseline, 24 h, and on the 1 month
      and 3 months post-baseline. RESULTS: In all the three groups, a significant
      reduction in PPD and gain in CAL were observed between baseline and 3 months
      follow-up (P< 0.05); however, at 3 months, change in PPD and CAL was more in
      Group II than Group III, but the difference was non-significant, and Group I
      (control) showed less changes in PPD and CAL than both experimental groups. Only
      one patient revealed positive value for CRP at baseline only, and hence could not
      be statistically analyzed. In all the three groups, the peak values for TLC count
      were observed at 24 h. At 1-month and 3-month intervals, a significant
      improvement in TLC and DLC counts was observed among the experimental (HA gel/SRP
      and Xan-CHX gel) groups as compared to control group (SRP alone).

PMID- 23853454
TI  - Detection of Enterococcus faecalis and Candida albicans in previously root-filled
      teeth in a population of Gujarat with polymerase chain reaction.
AB  - BACKGROUND: Micro-organisms are the primary causative agents of endodontic
      infections. Phenotype based procedures for bacterial identification has certain
      drawbacks especially, when investigating the microbiota of root-filled teeth.
      Thus, more sensitive methods like Polymerase chain reaction (PCR) can provide
      results that are more accurate and reliable for the microbial prevalence in the
      root filled teeth. AIM: In this study, we have investigated twenty symptomatic
      root-filled teeth with chronic apical periodontitis for the prevalence of
      Enterococcus faecalis and Candida albicans in the root filled teeth associated
      with symptomatic cases with or without periradicular lesions. MATERIALS AND
      METHODS: Microbiological samples were taken from the canals immediately after
      removal of previous gutta percha cones using aseptic techniques. After removal of
      root canal filling, samples were obtained with paper points placed in the canal.
      Paper points were transferred to a cryotube containing "Tris EDTA" buffer and
      immediately frozen at -20 degrees C. RESULTS: By PCR amplification of the samples
      using taxon specific primers, E. faecalis was found to be prevalent species,
      detected in 65% of the cases and C. albicans was detected in 35% of cases.
      CONCLUSION: The results of the study shows that geographical influence and
      dietary factors might have some role to play in the prevalence of the species
      like C. albicans and presence of E. faecalis confirming the assertion of previous
      culture-dependent and independent approaches for the microbiological survey of
      root filled teeth.

PMID- 23853455
TI  - Comparative evaluation of 15% ethylenediamine tetra-acetic acid plus cetavlon and
      5% chlorine dioxide in removal of smear layer: A scanning electron microscope
      study.
AB  - AIMS: The purpose of this study was to compare the efficacy of smear layer
      removal by 5% chlorine dioxide and 15% Ethylenediamine Tetra-Acetic Acid plus
      Cetavlon (EDTAC) from the human root canal dentin. MATERIALS AND METHODS: Fifty
      single rooted human mandibular anterior teeth were divided into two groups of 20
      teeth each and control group of 10 teeth. The root canals were prepared till F3
      protaper and initially irrigated with 2% Sodium hypochlorite followed by 1 min
      irrigation with 15% EDTAC or 5% Chlorine dioxide respectively. The control group
      was irrigated with saline. The teeth were longitudinally split and observed under
      Scanning electron microscope SEM (*2000). STATISTICAL ANALYSIS USED: The
      statistical analysis was done using General Linear Mixed Model. RESULTS: At the
      coronal thirds, no statistically significant difference was found between 15%
      EDTAC and 5% Chlorine dioxide in removing smear layer. In the middle and apical
      third region 15% EDTAC showed better smear layer removal ability than 5% Chlorine
      dioxide. CONCLUSION: Final irrigation with 15% EDTAC is superior to 5% chlorine
      dioxide in removing smear layer in the middle and apical third of radicular
      dentin.

PMID- 23853456
TI  - The effect of sub-antimicrobial dose-doxycycline periodontal therapy on serum
      inflammatory biomarker C-reactive protein levels in post-menopausal Women: A 2
      year, double-blinded, randomized clinical trial.
AB  - BACKGROUND: Periodontitis has been reported to be associated with coronary artery
      disease. Research is needed to determine whether therapies that improve
      periodontal health also reduce systemic marker of inflammation associated with
      both diseases. AIM: To determine whether sub-antimicrobial dose-doxycycline (SDD)
      therapy can reduce systemic serum inflammatory biomarker C-reactive protein (CRP)
      in post-menopausal women who have chronic periodontitis. SETTINGS AND DESIGN: The
      study randomly assigned 128 eligible post-menopausal women with chronic
      periodontitis to a 90-day, twice-daily regimen of SDD or placebo tablets
      evaluated for 2 years, as an adjunct to periodontal maintenance therapy.
      MATERIALS AND METHODS: The study assayed blood samples for inflammatory mediators
      at baseline, 1 year, and 2 years. CRP was measured using a high-sensitivity
      enzyme-linked immunosorbent assay. RESULTS: SDD treatment reduced median high
      sensitivity CRP by 18% (primary outcome = 0.02). CONCLUSION: Ninety-day SDD
      regimen in post-menopausal women significantly reduced the serum inflammatory
      biomarker CRP over a 2-year period.

PMID- 23853457
TI  - Hinged and sectional complete dentures for restricted mouth opening: A case
      report and review.
AB  - Restricted mouth opening is a definite prosthodontic hindrance to carry out
      treatment successfully. Restricted mouth opening can be due to many reasons such
      as microstomia, oral submucous fibrosis, some genetic disorder, and as a result
      of some surgical treatment. In the past, various techniques for prosthetic
      rehabilitation of limited oral opening have been tried such as surgeries, use of
      dynamic opening devices, magnetic devices, and modification of denture design.
      Here we present; a simplified technique and simple design for fabrication of
      maxillary hinged and mandibular hinged and sectional complete denture for a
      patient with restricted mouth opening due to oral submucous fibrosis. 

PMID- 23853458
TI  - Giant sialoliths of submandibular gland duct: Report of two cases with unusual
      shape.
AB  - Giant sialoliths are classified as those exceeding 15 mm in any one dimension.
      Although, large sialoliths have been described in the body of salivary glands,
      they are rarely found in the salivary ducts, particularly when the patients have
      no painful symptoms. Sialolithiasis is one of the most common diseases of the
      salivary glands in middle-aged patients and approximately 80% of all reported
      cases of sialoliths occur in the submandibular gland. Here, we report two cases
      of giant sialolith of submandibular gland duct. Interestingly, sialolith found in
      one of our cases had an unusual similarity with the canine tooth and mimicking it
      in both size and shape. In both cases the calculus was removed surgically via
      intraoral approach. No recurrence was seen in any of the cases on follow-up. 

PMID- 23853459
TI  - A modified surgical approach to a case of mandibular fracture in a 5-year-old
      girl.
AB  - Injuries to the face are far more uncommon than other injuries in children.
      However, when they occur they can pose considerable management challenges to
      concerned specialists and the subsequent functional and esthetic impact to the
      growing child can be overwhelming. Here is a report of a 5-year-old girl
      diagnosed with fracture of the body of the mandible and an associated fracture of
      the parasymphysis. This paper presents a unique treatment modality considering
      the various anatomic and developmental factors in such young children. 

PMID- 23853460
TI  - Clinical management of a complicated crown-root fracture using autogenous tooth
      fragment: A biological restorative approach.
AB  - Trauma resulting in crown-root fracture is one of the most challenging fracture
      types. However, biologic width involvement should be carefully evaluated.
      Reattachment of tooth fragment to a fractured tooth remains as the treatment of
      choice because of its simplicity, natural esthetics, and conservation of tooth
      structure. The reattachment procedure using composite resin should be considered
      if the subgingival fracture can be exposed to provide isolation. This report
      presents a case of complicated crown-root fracture of permanent maxillay left
      central incisor, involving the biologic width in a 10-year-old girl. The
      traumatized tooth was treated endodontically. Access to the subgingival margins
      was gained by orthodontic extrusion followed by gingivectomy. The fractured
      fragment was reattached using bonding system and composite resin. 

PMID- 23853461
TI  - Non-familial Cherubism.
AB  - Cherubism is a rare, self-limiting disease that usually affects jaws of pediatric
      population and is characterized by diffuse, bilateral and multilocular bony
      enlargement of jaws with a typical radiographic and histopathological appearance.
      Here, we describe a case of an 8-year-old child without any family history of
      this genetic disorder. 

PMID- 23853462
TI  - An organized start to implant-supported prosthesis.
AB  - Various treatment options are available for rehabilitating the complete
      edentulous patients with implants. However, due consideration for the prosthesis
      is not given prior to implant surgery. This can result in implant being placed in
      locations that do not provide the best esthetic and functional result. Incorrect
      implant localization and angle are the primary cause of non-axial loading and may
      contribute to loss of Osseo-integration. For predictable outcome, the treatment
      should begin with visualizing the end result. A step-wise pre-implant surgery
      evaluation is necessary to achieve the objectives. This is a case report of a
      completely edentulous patient who was treated with fixed implant prosthesis
      following various steps in the pre-implant surgery evaluation. 

PMID- 23853463
TI  - Concrescent triplets involving primary anterior teeth.
AB  - Odontogenesis is a complex process wherein more than 200 genes are known to play
      a significant role in tooth development. An imbalance can lead to an abnormality
      in the number, size, shape or structure of the developing tooth/teeth. The
      presence of an extra dental lamina forms a supernumerary tooth. The supernumerary
      teeth are of two types: A rudimentary tooth where the supernumerary tooth does
      not resemble any tooth in the normal series or a supplemental tooth in which this
      anomalous tooth resembles one in the normal series. It is also very rare to
      encounter triple teeth in primary dentition. The union of these teeth may be
      through fusion, gemination, concrescence or a combination of fusion and
      gemination. Presented is a rare case of concrescence involving maxillary
      deciduous incisors and a supplemental tooth in a 7-year-old boy. The differential
      diagnosis, etiology, and complications of primary anterior triple teeth are
      discussed. 

PMID- 23853464
TI  - A gingival manifestation of histoplasmosis leading diagnosis.
AB  - Histoplasmosis is a world-wide distributed deep mycosis caused by Histoplasma
      capsulatum which has been endemic in many countries. We present a case involving
      an immunocompetent man evidencing the necessity of a multidisciplinary approach
      and rational requisition of exams. The disease has started as a pulmonary disease
      mimicking tuberculosis, although the exams have been negative. Immunodiffusion
      test indicate histoplasmosis, not confirmed by culture of sputum. After days the
      patient was forwarded by a private doctor for evaluation of oral lesions at our
      Department of Stomatology. An incisional biopsy revealed a nonspecific
      granulomatous inflammation and the Grocott-Gomori methenamine silver stain
      identified scarce oval structures that could represent fungal yeast. Sampling
      oral lesions with swab, it was observed the typical growth of H. capsulatum on
      culture. This case highlights the importance of doctor's integration diagnosing
      histoplasmosis, while a wide spectrum of clinical manifestations should be
      expected. Oral lesions may be the critical manifestation leading diagnosis. 

PMID- 23853465
TI  - An unusual case of idiopathic gingival fibromatosis.
AB  - Idiopathic gingival fibromatosisis, a condition of undetermined cause can develop
      as an isolated disorder, but mostly it is associated with some syndrome. It
      usually begins at the time of eruption of permanent teeth but can develop with
      the eruption of deciduous dentition and rarely present at birth. This case report
      describes an unusual case of non-syndromic generalized idiopathic gingival
      fibromatosis in a 15-year-old male present since birth. Surgical treatment in the
      form of ledge and wedge procedure with internal bevel gingivectomy was performed.
      No recurrence of enlargement was seen after 2 years of follow-up. 

PMID- 23853466
TI  - Van der Woude syndrome: Management in the mixed dentition.
AB  - This article presents the case of a patient with Van der Woude syndrome treated
      with orthodontic and orthopedic intervention in the mixed dentition stage. The
      patient had a bilateral cleft of the lip and alveolus accompanied by lip pits on
      the lower lip. Intra-orally, there was bilateral anterior and posterior cross
      bite with a collapsed maxilla. The maxillary transverse deficiency was managed
      with orthopedic expansion and the second phase of treatment involved secondary
      alveolar bone grafting followed by retention with functional regulator-3. The
      mild maxillary retrognathia and deficient lip support was managed with dental
      compensation. 

PMID- 23853467
TI  - Odonto calcifying cyst.
AB  - The calcifying odontogenic cyst (COC) is reported to be associated with odontoma
      in 24% of cases. Separation of the cases of calcifying odontogenic cyst
      associated with odontoma (COCaO) may lead to a better understanding of the
      pathogenesis of this lesion. The literature revealed 52 cases of COCaO. The male
      to female ratio was 1:1.9, with a mean age of 16 years. Most common location was
      the maxilla (61.5%). The radiographic appearance of most cases (80.5%) was a well
      defined, mixed radiolucent-radiopaque lesion. Histologically, the lesions
      consisted of a single large cyst with tooth-like structures as an integral part,
      giving the impression of a single lesion. In addition to the unique histologic
      features, differences in gender and distribution were found between the cases of
      COCaO and those of simple COC. COCaO may be regarded as a separate entity and
      classified as a benign, mixed odontogenic tumor. The term odontocalcifying
      odontogenic cyst is suggested. 

PMID- 23853468
TI  - Aesthetic rehabilitation with multiple loop connectors.
AB  - Patients with a missing tooth along with diastema have limited treatment options
      to restore the edentulous space. The use of a conventional fixed partial denture
      (FPD) to replace the missing tooth may result in too wide anterior teeth leading
      to poor esthetics. The diastema resulting from the missing central incisors can
      be managed with implant-supported prosthesis or FPD with loop connectors. An old
      lady reported with chief complaints of missing upper anterior teeth due to
      trauma. Her past dental history revealed that she was having generalized spacing
      between her upper anterior teeth. Considering her esthetic requirement of
      maintaining the diastema between 12, 11, 22, and 21, the treatment option of 06
      units porcelain fused to metal FPD from canine to canine with intermittent loop
      connectors between 21, 22, 11, 12 was planned. Connectors basically link
      different parts of FPDs. The modified FPD with loop connectors enhanced the
      natural appearance of the restoration, maintained the diastemas and the proper
      emergence profile, and preserve the remaining tooth structure of abutment teeth.
      This clinical report discussed a method for fabrication of a modified FPD with
      loop connectors to restore the wide span created by missing central incisors. 

PMID- 23853469
TI  - Fracture of the styloid process associated with the mandible fracture.
AB  - Fracture of the styloid process (SP) of temporal bone is an uncommon injuries.
      Fracture of the SP can be associated with the facial injuries including mandible
      fracture. However, injury to the SP may be concealed and missed diagnosis may
      lead to the improper or various unnecessary treatments. A rare case of SP
      fracture associated with the ipsilateral mandibular fracture and also the
      diagnostic and management considerations of the SP fracture are discussed. 

PMID- 23853470
TI  - Cowden syndrome- Clinico-radiological illustration of a rare case.
AB  - Cowden syndrome (CS) or multiple hamartoma syndrome is an infrequent
      genodermatoses, which is inherited as an autosomal dominant trait resulting from
      the mutation in the Phosphatase and Tensin homolog gene on the arm 10q and is
      principally characterized by multiple hamartomas with an increased risk of
      development of malignancies. Facial and oral signs are remarkable in the form of
      multiple papules and trichilemmomas on the face. We report one such rare case of
      CS in a 19-year-old patient who was diagnosed on the basis of her oral mucosal
      lesions and was further investigated and diagnosed with other hamartomas. The
      present case report signifies the responsibility of the oral physician in the
      early diagnosis of this progressive pathological syndrome as it leaves its
      footmark in the oral cavity in the form of oral mucosal lesions. 

PMID- 23853471
TI  - Esthetic rehabilitation of discolored anterior teeth with porcelain veneers.
AB  - The common man is bombarded by the media extolling the virtues of "the perfect
      smile." In the 21(st) century of esthetic dentistry, fractured, malformed,
      malposed, and discolored teeth can be changed and restored to highly desirable
      form due to introduction of wide range of esthetic materials and techniques.
      Porcelain veneers is a conservative method of restoring the appearance of
      discolored, pitted teeth, and teeth with diastemas that provide extremely good
      esthetic results. A 21-year-old female patient with staining in anterior teeth
      had reported to the Department of Prosthodontics for esthetic rehabilitation. The
      patient was treated with porcelain veneers on maxillary anterior teeth. The
      patient was satisfied with the enhanced esthetic appearance. 

PMID- 23853472
TI  - Inicial nasal mucosa detachment using piezoelectric device in the Le Fort I
      osteotomy: A technical note.
AB  - In maxillary Le Fort I type osteotomy the detachment of the nasal mucosa should
      be done carefully. Piezoelectric surgery contributed much to increase the safety
      of osteotomies, despite the initial advantage of minimizing the risk of injury in
      nervous tissue, mainly in bilateral sagittal split osteotomy; we use the
      piezoelectric device for the initial detachment of the nasal mucosa in the
      maxillary osteotomy. 

PMID- 23853473
TI  - Over the journal impact factor.

PMID- 23853474
TI  - Peer review in scholarly biomedical journals: a few things that make a big
      difference.

PMID- 23853475
TI  - Selecting your editorial board: maintaining standards.

PMID- 23853476
TI  - Recent increase in autism and ADHD: true or inflated?

PMID- 23853477
TI  - Osteoporotic hip fracture in the elderly patients: physicians' views.

PMID- 23853478
TI  - Current levels of conflict of interest disclosure in medical publications from
      Korea.
AB  - Medical research should be fully transparent. The aims of this study were to
      determine the prevalence of author-related conflict of interest (COI) policies
      and evaluate the actual state of COI disclosure in Korean medical journals. To
      determine the prevalence of author-related COI policies, we examined the 198
      medical journals listed in the KoreaMed database. To investigate the actual state
      of COI disclosures in published papers, we analyzed the publications in a
      representative medical journal, the Journal of the Korean Medical Science, from
      the perspective of the relevance of the ethics of COI disclosure. A total of 164
      (82.8%) journals required an author's statement of COI as a criterion for
      publication. Of these 164, most of them focused on financial COI, with 101
      (61.6%) presenting the information related to COI disclosures as a separate
      paragraph with a clear title. We identified 114 articles published by the Journal
      of the Korean Medical Science over a seven-year period, from January, 2006 to
      December, 2012. Of these, 65 papers (57%) included an author's statement of COI.
      We found that the policies of Korean medical journals regarding the disclosure of
      author COIs are still behind the internationally suggested level. 

PMID- 23853479
TI  - Epidemiological characteristics of the first water-borne outbreak of
      cryptosporidiosis in Seoul, Korea.
AB  - The first case of human cryptosporidiosis was reported in Korea in 1995; however,
      an outbreak of Cryptosporidium has not been reported in Korea until now. This
      paper describes the first outbreak of cryptosporidiosis in Korea. On May 24,
      2012, a local public health center filed a report on 126 residents with
      gastrointestinal symptoms in an old apartment complex in Seoul. Epidemiological
      investigations were implemented on 125 of the 126 patients. The patients were
      reported continuously over a period of 22 days. Diarrhea was the most common
      clinical symptom, and lasted for 5 days on average. The tap water was the only
      common exposure of the patients. During the environmental investigation it was
      discovered that the water and septic tanks were situated closely and that the
      waste water pipes were corroded where they passed over the water pipes.
      Cryptosporidium parvum was detected in 3 of the 7 stool specimens by PCR-RFLP. A
      number of Cryptosporidium oocysts were also detected in the water specimens from
      the water tank. In conclusion, Cryptosporidium parvum was the key causal pathogen
      of this outbreak. It is presumed that the tap water was contaminated by a sewage
      leak from the aged pipelines. 

PMID- 23853480
TI  - Causes of death and risk factors for mortality among HIV-infected patients
      receiving antiretroviral therapy in Korea.
AB  - A retrospective study was conducted to determine the mortality, causes and risk
      factors for death among HIV-infected patients receiving antiretroviral therapy
      (ART) in Korea. The outcomes were determined by time periods, during the first
      year of ART and during 1-5 yr after ART initiation, respectively. Patients lost
      to follow-up were traced to ascertain survival status. Among 327 patients
      initiating ART during 1998-2006, 68 patients (20.8%) died during 5-yr follow-up
      periods. Mortality rate per 100 person-years was 8.69 (95% confidence interval,
      5.68-12.73) during the first year of ART, which was higher than 4.13 (95%
      confidence interval, 2.98-5.59) during 1-5 yr after ART. Tuberculosis was the
      most common cause of death in both periods (30.8% within the first year of ART
      and 16.7% during 1-5 yr after ART). During the first year of ART, clinical
      category B and C at ART initiation, and underlying malignancy were significant
      risk factors for mortality. Between 1 and 5 yr after ART initiation, CD4 cell
      count <= 50 cells/uL at ART initiation, hepatitis B virus co-infection, and visit
      constancy <= 50% were significant risk factors for death. This suggests that
      different strategies to reduce mortality according to the time period after ART
      initiation are needed. 

PMID- 23853481
TI  - Clinical and molecular epidemiology of community-onset bacteremia caused by
      extended-spectrum beta-lactamase-producing Escherichia coli over a 6-year period.
AB  - Although extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC)
      has emerged as a significant community-acquired pathogen, there is little
      epidemiological information regarding community-onset bacteremia due to ESBL-EC.
      A retrospective observational study from 2006 through 2011 was performed to
      evaluate the epidemiology of community-onset bacteremia caused by ESBL-EC. In a
      six-year period, the proportion of ESBL-EC responsible for causing community
      onset bacteremia had increased significantly, from 3.6% in 2006 to 14.3%, in
      2011. Of the 97 clinically evaluable cases with ESBL-EC bacteremia, 32 (33.0%)
      were further classified as healthcare-associated infections. The most common site
      of infection was urinary tract infection (n=35, 36.1%), followed by biliary tract
      infections (n=29, 29.9%). Of the 103 ESBL-EC isolates, 43 (41.7%) produced CTX-M
      14 and 36 (35.0%) produced CTX-M-15. In the multilocus sequence typing (MLST)
      analysis of 76 isolates with CTX-M-14 or -15 type ESBLs, the most prevalent
      sequence type (ST) was ST131 (n=15, 19.7%), followed by ST405 (n=12, 15.8%) and
      ST648 (n=8, 10.5%). No significant differences in clinical features were found in
      the ST131 group versus the other group. These findings suggest that epidemic ESBL
      EC clones such as CTX-M-14 or -15 type ESBLs and ST131 have disseminated in
      community-onset infections, even in bloodstream infections, which are the most
      serious type of infection. 

PMID- 23853482
TI  - Transglutaminase 2 expression predicts progression free survival in non-small
      cell lung cancer patients treated with epidermal growth factor receptor tyrosine
      kinase inhibitor.
AB  - Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance
      and in the constitutive activation of nuclear factor kappa B (NF-kappaB). We
      investigated the association of non-small cell lung cancer (NSCLC) treatment
      efficacy with TG2 and NF-kappaB expression in 120 patients: 102 with
      adenocarcinoma and 18 with other histologic types. All patients underwent
      surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based
      doublet chemotherapy as first-line treatment and 29 receiving epidermal growth
      factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and
      NF-kappaB expression values were calculated semiquantitatively. The median TG2
      value was 50 (range, 0-300) and the median NF-kappaB value was 20 (range, 0-240).
      Disease-free survival did not differ between the low- and high-TG2 groups. Among
      patients who received palliative platinum-based doublet chemotherapy, progression
      free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group
      (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS
      was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0
      months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI,
      PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013).
      TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR
      TKI. 

PMID- 23853483
TI  - Changes in body composition predict homocysteine changes and hyperhomocysteinemia
      in Korea.
AB  - Cardiovascular disease (CVD) is the primary cause of death in Korea.
      Hyperhomocysteinemia confers an independent risk for CVD comparable to the risk
      of smoking and hyperlipidemia. The purpose of this study was to assess the effect
      of cardiovascular risk factors and body composition change on homocysteine (Hcy)
      levels in Korean men and women. The association between body composition and Hcy
      levels was investigated in a 2-yr prospective cohort study of 2,590 Koreans (mean
      age 45.5+/-9.6 yr). There were 293 cases of hyperhomocysteinemia (>14 uM/L) at
      follow-up. Increases in total body fat proportion and decreases in lean body mass
      (LBM) were significantly associated with increases in Hcy concentration after
      controlling for confounding factors. Further adjustments for behavioral factors
      showed that decreases in LBM were associated with Hcy increase. Decrease in LBM
      also predicted hyperhomocysteinemia at follow-up, after controlling for
      confounding factors. There was no significant association between change in body
      mass index (BMI) and Hcy concentrations over time. Hcy changes over time were
      related to change in LBM and body fat content, whereas BMI or weight change did
      not predict change in Hcy levels. Changes in ratio of LBM to total fat mass may
      contribute to hyperhomocysteinemia. 

PMID- 23853484
TI  - Genetic mutation in Korean patients of sudden cardiac arrest as a surrogating
      marker of idiopathic ventricular arrhythmia.
AB  - Mutation or common intronic variants in cardiac ion channel genes have been
      suggested to be associated with sudden cardiac death caused by idiopathic
      ventricular tachyarrhythmia. This study aimed to find mutations in cardiac ion
      channel genes of Korean sudden cardiac arrest patients with structurally normal
      heart and to verify association between common genetic variation in cardiac ion
      channel and sudden cardiac arrest by idiopathic ventricular tachyarrhythmia in
      Koreans. Study participants were Korean survivors of sudden cardiac arrest caused
      by idiopathic ventricular tachycardia or fibrillation. All coding exons of the
      SCN5A, KCNQ1, and KCNH2 genes were analyzed by Sanger sequencing. Fifteen
      survivors of sudden cardiac arrest were included. Three male patients had
      mutations in SCN5A gene and none in KCNQ1 and KCNH2 genes. Intronic variant
      (rs2283222) in KCNQ1 gene showed significant association with sudden cardiac
      arrest (OR 4.05). Four male sudden cardiac arrest survivors had intronic variant
      (rs11720524) in SCN5A gene. None of female survivors of sudden cardiac arrest had
      SCN5A gene mutations despite similar frequencies of intronic variants between
      males and females in 55 normal controls. Common intronic variant in KCNQ1 gene is
      associated with sudden cardiac arrest caused by idiopathic ventricular
      tachyarrhythmia in Koreans. 

PMID- 23853485
TI  - Percutaneous coronary intervention for acute myocardial infarction in elderly
      patients with renal dysfunction: results from the Korea Acute Myocardial
      Infarction Registry.
AB  - This study aimed to evaluate the effects of percutaneous coronary intervention
      (PCI) on short- and long-term major adverse cardiac events (MACE) in elderly (>75
      yr old) acute myocardial infarction (AMI) patients with renal dysfunction. As
      part of Korea AMI Registry (KAMIR), elderly patients with AMI and renal
      dysfunction (GFR<60 mL/min) received either medical (n=439) or PCI (n=1,019)
      therapy. Primary end point was in-hospital death. Secondary end point was MACE
      during a 1 month and 1 yr follow-up. PCI group showed a significantly lower
      incidence of in-hospital death (20.0% vs 14.3%, P=0.006). Short-term and long
      term MACE rates were higher in medical therapy group (31.9% vs 19.0%; 57.7% vs
      31.3%, P<0.001), and this difference was mainly attributed to cardiac death
      (29.3% vs 17.6%; 51.9% vs 25.0%, P<0.001). MACE-free survival time after
      adjustment was also higher in PCI group on short-term (hazard ratio, 0.67;
      confidence interval, 0.45-0.98; P=0.037) and long-term follow-up (hazard ratio,
      0.61, confidence interval, 0.45-0.83; P=0.002). In elderly AMI patients with
      renal dysfunction, PCI therapy yields favorable in-hospital and short-term and
      long-term MACE-free survival. 

PMID- 23853486
TI  - Small increases in plasma sodium are associated with higher risk of mortality in
      a healthy population.
AB  - Elevated blood pressure (BP) is the most common cause of cardiovascular disease.
      Salt intake has a strong influence on BP, and plasma sodium (pNa) is increased
      with progressive increases in salt intake. However, the associations with pNa and
      BP had been reported inconsistently. We evaluated the association between pNa and
      BP, and estimated the risks of all-cause-mortality according to pNa levels. On
      the basis of data collected from health checkups during 1995-2009, 97,009 adult
      subjects were included. Positive correlations between pNa and systolic BP,
      diastolic BP, and pulse pressure (PP) were noted in participants with pNa >=138
      mM/L (P<0.001). In participants aged >=50 yr, SBP, DBP, and PP were positively
      associated with pNa. In participants with metabolic syndrome components, the
      differences in SBP and DBP according to pNa were greater (P<0.001). A cumulative
      incidence of mortality was increased with increasing pNa in women aged >=50 yr
      during the median 4.2-yr-follow-up (P<0.001). In women, unadjusted risks for
      mortality were increased according to sodium levels. After adjustment, pNa >=145
      mM/L was related to mortality. The positive correlation between pNa and BP is
      stronger in older subjects, women, and subjects with metabolic syndrome
      components. The incidence and adjusted risks of mortality increase with
      increasing pNa in women aged >=50 yr. 

PMID- 23853487
TI  - Sarcopenia and obesity: gender-different relationship with functional limitation
      in older persons.
AB  - Age-related body composition changes such as sarcopenia and obesity affect
      functional decline in the elderly. We investigated the relationship between body
      composition parameters and functional limitation in older Korean adults. We
      enrolled 242 men and 231 women aged >= 65 yr from the Korean elderly cohort. We
      used appendicular skeletal muscle mass (ASM) divided by height(2) (ASM/Ht(2)) and
      ASM divided by weight (ASM/Wt). The isokinetic strength of knee extensor muscles
      were measured using an isokinetic device. Functional limitations were assessed
      using the Short Physical Performance Battery (SPPB) score less than nine. Men
      within the bottom tertile of ASM/Ht(2) confer an increased risk for functional
      limitation compared with those within the top tertile (OR, 6.24; 95% CI, 1.78
      22.0). However, in women, subjects within the lowest ASM/Wt tertile had a higher
      risk compared with those within the highest tertile instead of ASM/Ht(2) (OR,
      7.60; 95% CI, 2.25-25.7). Leg muscle strength remained the strong measure even
      after controlling for muscle mass only in women. Only large waist circumference
      was positively associated with functional limitation only in women. We might
      consider a different muscle index to assess functional limitation according to
      the gender. 

PMID- 23853488
TI  - Chronic obstructive pulmonary disease assessment test can predict depression: a
      prospective multi-center study.
AB  - This study was conducted to investigate the association between the chronic
      obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD
      patients. The Korean versions of the CAT and patient health questionnaire-9 (PHQ
      9) were used to assess COPD symptoms and depressive disorder, respectively. In
      total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence
      of depression was 23.8%. The CAT score correlated well with the PHQ-9 score
      (r=0.631; P<0.001) and was significantly associated with the presence of
      depression (beta+/-standard error, 0.452+/-0.020; P<0.001). There was a tendency
      toward increasing severity of depression in patients with higher CAT scores. By
      assessment groups based on the 2011 Global Initiative for Chronic Obstructive
      Lung Disease guidelines, the prevalence of depression was affected more by
      current symptoms than by airway limitation. The area under the receiver operating
      characteristic curve for the CAT was 0.849 for predicting depression, and CAT
      scores >=21 had the highest accuracy rate (80.6%). Among the eight CAT items,
      energy score showed the best correlation and highest power of discrimination. CAT
      scores are significantly associated with the presence of depression and have good
      performance for predicting depression in COPD patients. 

PMID- 23853489
TI  - Avoidable causes of delayed enteral nutrition in critically ill children.
AB  - To evaluate the incidence of delayed enteral nutrition (EN) and identify
      avoidable causes of delay, we retrospectively reviewed medical records of 200
      children (median age [range]; 37.5 [1-216] months) who stayed in the intensive
      care unit (ICU) for a minimum of 3 days. Among 200 children, 115 received EN
      following ICU admission with a median time of EN initiation of 5 days after
      admission. Of these, only 22 patients achieved the estimated energy requirement.
      A significant decrease in the final z score of weight for age from the initial
      assessment was observed in the non-EN group only (-1.3+/-2.17 to -1.57+/-2.35,
      P<0.001). More survivors than non-survivors received EN during their ICU stay
      (61.2% vs 30.0%, P=0.001) and received EN within 72 hr of ICU admission (19.8% vs
      3.3%, P=0.033). The most common reason for delayed EN was gastrointestinal (GI)
      bleeding, followed by altered GI motility and hemodynamic instability. Only eight
      cases of GI bleeding and one case of altered GI motility were diagnosed as active
      GI bleeding and ileus, respectively. This study showed that the strategies to
      reduce avoidable withholding EN are necessary to improve the nutrition status of
      critically ill children. 

PMID- 23853490
TI  - Clinical value of persistent but downgraded vesicoureteral reflux after
      dextranomer/hyaluronic acid injection in children.
AB  - We aimed to investigate the clinical value of persistent but downgraded
      vesicoureteral reflux (VUR) after dextranomer/hyaluronic acid (Dx/HA) injection
      in children. The medical records of 128 children (195 ureters) who underwent
      Dx/HA injections for VUR were reviewed. The incidences of pre- and post-operative
      febrile urinary tract infections (UTIs) were analyzed in children with or without
      persistent VUR on voiding cystourethrography (VCUG) 3 months postoperatively. The
      surgical results of VUR persistent children who underwent a single additional
      injection were assessed. The VUR resolved completely in 100 ureters (51.3%), was
      persistent in 95 ureters, and newly developed in 2 ureters. The incidence of
      pre/post-operative febrile UTIs were 0.35 +/- 0.39 per year and 0.07 +/- 0.32 per
      year in VUR resolved children (P < 0.001), and 0.76 +/- 1.18 per year and 0.20 +/
      0.61 per year in VUR persistent children (P < 0.001). A single additional Dx/HA
      injection (44 ureters) resolved VUR in 29 ureters (65.9%), and also reduced the
      VUR to grade I in 7 ureters (15.9%), II in 4 (9.1%), and III in 4 (9.1%). Even in
      children with persistent VUR after Dx/HA injection, the incidence of febrile UTIs
      decreased markedly. The VUR grade significantly decreases after single additional
      Dx/HA injection. 

PMID- 23853491
TI  - A nationwide epidemiological study of nocturnal enuresis in Korean adolescents
      and adults: population based cross sectional study.
AB  - We performed a nationwide epidemiological study to evaluate the prevalence and
      characteristics of nocturnal enuresis (NE) in Korean adolescents and adults. A
      questionnaire was sent via e-mail to 51,073 people aged 16-40 yr by stratified
      sampling according to age, sex, and region among a 200,000 internet survey panel
      pool. The questionnaire included following information; presence or absence of
      NE, frequency of NE, possible risk factors for NE, self-esteem scale score and
      depression score results, and measures for the treatment of NE. Among the 2,117
      responders, 54 (2.6%) had NE (>=1 enuretic episode within 6 months). Of 54
      bedwetters, 9.3% wet >=1 night per week and 20.5% wet >=1 per month. The
      prevalence rates remained relatively stable with no apparent trend of reduction
      with age. The presence of sleep disturbance, family history, urgency, or urge
      incontinence increased the probability of NE episode significantly. The self
      esteem score was lower (P=0.053) and the depression scale score was higher
      (P=0.003) in bedwetters compared with non-bedwetters. Overall 2.6% of Korean aged
      16-40 yr have NE. The higher rate of urgency and urge incontinence in adolescent
      and adult enuretics suggests that bladder function has an important role in
      adolescent and adult NE. 

PMID- 23853492
TI  - Quantitative in vivo detection of brain cell death after hypoxia ischemia using
      the lipid peak at 1.3 ppm of proton magnetic resonance spectroscopy in neonatal
      rats.
AB  - This study was performed to determine the accuracy of proton magnetic
      spectroscopy ((1)H-MRS) lipid peak as a noninvasive tool for quantitative in vivo
      detection of brain cell death. Seven day-old Sprague Dawley rats were subjected
      to 8% oxygen following a unilateral carotid artery ligation. For treatment,
      cycloheximide was given immediately after hypoxic ischemia (HI). Lipid peak was
      measured using (1)H-MRS at 24 hr after HI, and then brains were harvested for
      fluorocytometric analyses with annexin V/propidium iodide (PI) and fluorescent
      probe JC-1, and for adenosine-5'-triphosphate (ATP) and lactate. Increased lipid
      peak at 1.3 ppm measured with (1)H-MRS, apoptotic and necrotic cells, and loss of
      mitochondrial membrane potential (DeltaPsi) at 24 hr after HI were significantly
      improved with cycloheximide treatment. Significantly reduced brain ATP and
      increased lactate levels observed at 24 hr after HI showed a tendency to improve
      without statistical significance with cycloheximide treatment. Lipid peak at 1.3
      ppm showed significant positive correlation with both apoptotic and necrotic
      cells and loss of DeltaPsi, and negative correlation with normal live cells.
      Lipid peak at 1.3 ppm measured by (1)H-MRS might be a sensitive and reliable
      diagnostic tool for quantitative in vivo detection of brain cell death after HI. 

PMID- 23853493
TI  - Print media coverage of post-traumatic stress disorder: content analysis of three
      major Korean newspapers.
AB  - The print media is still one of major sources for health-related information. To
      shed light on how the media accurately delivers information for post-traumatic
      stress disorder (PTSD), we searched the newspaper articles and analyzed their
      contents for accuracy in the description of symptoms, causes, and treatment of
      PTSD. The articles featuring PSTD were searched from the very first available to
      2010 at on-line search systems of three major Korean newspapers. A total of 123
      articles appeared and the first article appeared in 1984. The number of articles
      steadily increased till the early 2000s but we found the robust increase in the
      late 2000s. Among the mentioned symptoms of PTSD: re-experience (39%) was most
      common, followed by avoidance or numbing (28%) and hyperarousal (22%). Of the 29
      articles mentioning treatment of PTSD, 13 mentioned psychotherapy only and 11
      mentioned both psychotherapy and medication equally. However, the psychotherapies
      mentioned were non-specific and only five articles mentioned any empirically
      supported therapies. The number of articles on PTSD in Korean newspapers has
      continually increased during the last three decades. However, the quality of
      information on the treatment of PTSD was questionable. 

PMID- 23853494
TI  - Recent trends (1991-2010) of metastatic skin cancers in Korea.
AB  - The incidence of overall cancer has increased over time. The incidence of top
      ranking cancers has changed in the 1990s and the 2000s. However, few studies have
      evaluated the trends in metastatic skin cancers during this period. We evaluated
      the recent trends in incidence, peak age and location of metastatic skin cancers
      from 1991 to 2010. This 20-yr survey was divided into two decades to determine
      the trends by comparing the statistics. Out of 694,466 outpatients (1991-2010),
      174 (0.025%) were diagnosed with metastatic skin cancer. The incidence of
      metastatic skin cancer increased significantly from 20.64 per 100,000 outpatients
      in the 1990s to 28.70 per 100,000 outpatients in the 2000s (P = 0.030). The peak
      age of skin metastasis shifted from the 40s to the 50s in women, and from the 50s
      to the 60s in men. The percentage of metastatic skin cancers originating from
      intra-abdominal organs increased from 10% in the 1990s to 23.1% in the 2000s (P =
      0.027). The percentage of metastatic skin cancers located on the abdomen
      increased from 7.1% in the 1990s to 15.4% in the 2000s (P = 0.011). The higher
      proportion of metastatic skin cancers located on the abdomen may be related to
      the increase in skin metastases from intra-abdominal organs. 

PMID- 23853495
TI  - Morbidity and mortality in Jeju residents over 50-years of age with hip fracture
      with mean 6-year follow-up: a prospective cohort study.
AB  - This prospective cohort study was performed to estimate the morbidity and
      mortality with 790 patients over 50-yr of age that sustained a femoral neck or
      intertrochanteric fracture from 2002 to 2006, followed-up for a mean of 6 yr
      (range, 4 to 9 yr). Crude and annual standardized mortality ratios (SMRs) were
      calculated; and mortalities in the cohort and the age and sex matched general
      population were compared. The risk factors on mortality and activities pre- and
      post-injury were assessed. Accumulated mortality was 16.7% (132 patients) at 1
      yr, 45.8% (337 patients) at 5 yr, and 60% (372 patients) at 8 yr. SMR at 5 yr
      post-injury was 1.3 times that of the general population. Multivariate analysis
      demonstrated that age (OR, 1.074; 95% CI, 1.050-1.097; P<0.001), woman (OR,
      1.893; 95% CI, 1.207-2.968; P=0.005), and medical comorbidity (OR, 1.334; 95% CI,
      1.167-1.524 P<0.001) were independently associated with mortality after hip
      fracture. Only 59 of the 150 patients (39.3%) who were able to ambulate normally
      outdoors at preinjury retained this ability at final follow-up. Patients with a
      hip fracture exhibits higher mortality at up to 5 yr than general population. Age
      and a preinjury comorbidity are associated with mortality. 

PMID- 23853496
TI  - Cross-cultural adaptation of the Korean version of the Boston carpal tunnel
      questionnaire: its clinical evaluation in patients with carpal tunnel syndrome
      following local corticosteroid injection.
AB  - The aim of this study was to assess and validate the Korean version of the Boston
      Carpal Tunnel Questionnaire (K-BCTQ) in patients with carpal tunnel syndrome
      (CTS). After translation and cultural adaptation of the BCTQ to a Korean version,
      the K-BCTQ was administered to 54 patients with CTS; it was administered again
      after 2 weeks to assess reliability. Additionally, we administered K-DASH and EQ
      5D to assess construct-validity. In a prospective study of responsiveness to
      clinical change, 29 of 54 patients were treated by ultrasonography-guided local
      corticosteroid injection therapy. The internal consistency of the K-BCTQ was high
      (Cronbach's alpha: 0.915) and the intra-class correlation coefficients were 0.931
      for the symptom severity scale (P<0.001) and 0.844 for the functional severity
      scale (P<0.001). The construct-validity between the symptom severity scale and
      the K-DASH, and between the functional severity scale and the K-DASH were
      significantly correlated (both P<0.001). Clinical improvement was noted in 29
      patients with injection therapy. The effect size of symptom severity was 0.67,
      and that of functional severity was 0.58. In conclusion, the K-BCTQ shows good
      reliability, construct-validity, and acceptable responsiveness after local
      corticosteroid injection therapy (Clinical trial number, KCT0000050). 

PMID- 23853497
TI  - First imported case of skin infection caused by PVL-positive ST30 community
      associated methicillin-resistant Staphylococcus aureus clone in a returning
      Korean traveler from the Philippines.
AB  - Although pandemic community-associated (CA-) methicillin-resistant Staphylococcus
      aureus (MRSA) ST30 clone has successfully spread into many Asian countries, there
      has been no case in Korea. We report the first imported case of infection caused
      by this clone in a Korean traveler returning from the Philippines. A previously
      healthy 30-yr-old Korean woman developed a buttock carbuncle while traveling in
      the Philippines. After coming back to Korea, oral cephalosporin was given by a
      primary physician without any improvement. Abscess was drained and MRSA strain
      isolated from her carbuncle was molecularly characterized and it was confirmed as
      ST30-MRSA-IV. She was successfully treated with vancomycin and surgery. Frequent
      international travel and migration have increased the risk of international
      spread of CA-MRSA clones. The efforts to understand the changing epidemiology of
      CA-MRSA should be continued, and we should raise suspicion of CA-MRSA infection
      in travelers with skin infections returning from CA-MRSA-endemic countries. 

PMID- 23853498
TI  - Small bowel pseudomelanosis associated with oral iron therapy.
AB  - An accumulation of pigment deposits on mucosa, called melanosis or
      pseudomelanosis, of the small bowel is observed infrequently during endoscopic
      examination. We describe 6 cases of small bowel pseudomelanosis; the possible
      etiology of which was chronic iron intake. We observed numerous brown spots in
      duodenum, jejunum, and terminal ileum during upper and lower endoscopy.
      Interestingly, all patients have been taking oral iron for several years.
      Histology showed pigment depositions within macrophages of the lamina propria and
      a positive Prussian blue stain indicating hemosiderin deposition. Herein, we
      demonstrate that long term iron therapy may result in pseudomelanosis of small
      bowel, such as duodenum, jejunum, and ileum. 

PMID- 23853499
TI  - Osteogenesis imperfecta Type VI with severe bony deformities caused by novel
      compound heterozygous mutations in SERPINF1.
AB  - Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders
      characterized by bone fragility, frequent fractures, and low bone mass.
      Dominantly inherited COL1A1 or COL1A2 mutations appear to be causative in the
      majority of OI types, but rare recessively inherited genes have also been
      reported. Recently, SERPINF1 has been reported as another causative gene in OI
      type VI. To date, only eight SERPINF1 mutations have been reported and all are
      homozygous. Our patient showed no abnormalities at birth, frequent fractures,
      osteopenia, and poor response on pamidronate therapy. At the time of her most
      recent evaluation, she was 8 yr old, and could not walk independently due to
      frequent lower-extremity fractures, resulting in severe deformity. No clinical
      signs were seen of hearing impairment, blue sclera, or dentinogenesis imperfecta.
      In this study, we describe the clinical and radiological findings of one Korean
      patient with novel compound heterozygous mutations (c.77dupC and c.421dupC) of
      SERPINF1. 

PMID- 23853500
TI  - A case of myotonic dystrophy with electrolyte imbalance.
AB  - Type 1 myotonic dystrophy (DM1) is an autosomal-dominant inherited disorder with
      a multisystem involvement, caused by an abnormal expansion of the CTG sequence of
      the dystrophic myotonia protein kinase (DMPK) gene. DM1 is a variable multisystem
      disorder with muscular and nonmuscular abnormalities. Increasingly, endocrine
      abnormalities, such as gonadal, pancreatic, and adrenal dysfunction are being
      reported. But, Electrolytes imbalance is a very rare condition in patients with
      DM1 yet. Herein we present a 42-yr-old Korean male of DM1 with abnormally
      elevated serum sodium and potassium. The patient had minimum volume of maximally
      concentrated urine without water loss. It was only cured by normal saline
      hydration. The cause of hypernatremia was considered by primary hypodipsia.
      Hyperkalemic conditions such as renal failure, pseudohyperkalemia, cortisol
      deficiency and hyperkalemic periodic paralysis were excluded. Further endocrine
      evaluation suggested selective hyperreninemic hypoaldosteronism as a cause of
      hyperkalemia. 

PMID- 23853501
TI  - Comment on: Risk of pancreatic cancer in relation to ABO blood group and
      hepatitis C virus infection in Korea: a case-control study.

PMID- 23853502
TI  - A Novel Space Partitioning Algorithm to Improve Current Practices in Facility
      Placement.
AB  - In the presence of naturally occurring and man-made public health threats, the
      feasibility of regional bio-emergency contingency plans plays a crucial role in
      the mitigation of such emergencies. While the analysis of in-place response
      scenarios provides a measure of quality for a given plan, it involves human
      judgment to identify improvements in plans that are otherwise likely to fail.
      Since resource constraints and government mandates limit the availability of
      service provided in case of an emergency, computational techniques can determine
      optimal locations for providing emergency response assuming that the uniform
      distribution of demand across homogeneous resources will yield and optimal
      service outcome. This paper presents an algorithm that recursively partitions the
      geographic space into sub-regions while equally distributing the population
      across the partitions. For this method, we have proven the existence of an upper
      bound on the deviation from the optimal population size for sub-regions.

PMID- 23853504
TI  - Overlapping syndromes in laminopathies: a meta-analysis of the reported
      literature.
AB  - Mutations on the LMNA gene are responsible for an heterogeneous group of
      diseases. Overlapping syndromes related to LMNA gene alterations have been
      extensively reported. Study scope is to perform a systematic analysis of the
      overlapping syndromes so far described and to try to correlate the clinical
      features to the associated genetic alterations. We evaluated all the dominant
      overlapping syndromes reported by means of a PubMed search and by the analysis of
      the main databases containing the pathogenic LMNA gene variations and the
      associated diseases. Metabolic alterations in association to skeletal and/or
      cardiac alterations proved to be the most frequent overlap syndrome. Overlapping
      syndromes are mostly associated to inframe mutations in exons 1, 2, 8 and 9.
      These data further improve the understanding of the pathogenesis of
      laminopathies. 

PMID- 23853505
TI  - Advances in basic and clinical research in laminopathies.
AB  - Lamins (LMNA) are the main proteins of the nuclear lamina considered to be the
      ancestors of all intermediate filament proteins. They form complex protein
      assemblies with integral proteins of the inner nuclear membrane, transcriptional
      regulators, histones and chromatin modifiers. During recent years, interest in
      lamins has greatly increased due to the identification of many distinct heritable
      human disorders associated with lamin mutations. These disorders, collectively
      termed laminopathies, range from muscular dystrophies to premature aging. They
      may affect muscle, fat, bone, nerve and skin tissues. The workshop was addressed
      to understand lamin organization and its roles in nuclear processes, mutations in
      lamins affecting cell and tissues functions, the biology of the nucleus and
      laminopathic disease mechanisms, all aspects important for designing future
      therapies. 

PMID- 23853506
TI  - An Italian kindred with FALS due to c.149T>C mutation in the SOD1 gene: case
      report of an affected family member.
AB  - We report the first Italian kindred with Familial Amyotrophic Lateral Sclerosis
      (FALS) due to c.149T>C mutation in the exon 5 of superoxide dismutase-1 (SOD1)
      gene. The proband was a 49-year-old woman who came to our observation because of
      an history of progressive limbs weakness and gait impairment. She belonged to a
      family of 24 affected members. The prevalent phenotype of the affected members
      was characterized by slowly progressive spinal impairment with proximal
      distribution of weakness, and bulbar involvement in advanced stages. We briefly
      reviewed the few previous reports about the same SOD1 mutation and discussed the
      hypothesis that structural instability of the mutant codon 149 protein may
      underlie some toxic effects significantly involved in FALS pathogenesis. 

PMID- 23853507
TI  - A heroin addict with focal weakness.
AB  - A 24-year-old female with 5 year history of heroin abuse experienced painless
      stiffness of elbow joints and weakness of shoulder and upper limb muscles. She
      was injecting herself 4-6 times daily alternatively in the upper extremities,
      sparing the lower limbs. Electromyography (EMG) showed myopathic changes in
      clinically affected and unaffected muscles. Magnetic resonance imaging (MRI)
      revealed muscle fibrosis in directly injected muscles, whereas in subcutaneous
      fat and within muscles of anterior and posterior compartments of both thighs, not
      directly injected, there were signal changes supportive of oedema and
      inflammation. EMG and MRI were congruent in showing abnormalities in muscles not
      directly injected, suggesting long distant effects of heroin or adulterants with
      a mechanism either toxic or immunologically mediated. 

PMID- 23853508
TI  - The transformation of the photo-thermo sensitive genic male-sterile line 261S of
      rice via an expression vector containing the anti-Waxy gene.
AB  - Transgenic photo-thermo sensitive genic male sterility Oryza sativa L. cv. "261S"
      plants with the anti-Waxy gene were successfully obtained using an Agrobacterium
      tumefaciens-mediated co-transformation method. Marker-free homozygous transgenic
      lines with the anti-Waxy gene were obtained. The setting seed rates of the
      transgenic plants via self-pollination or via crossing with the restorer line
      WX99075 rice and the 1000-grain weight of the transgenic plants and the F2 hybrid
      seeds obtained by crossing the transgenic or non-transgenic plants with the
      restorer line WX99075 rice, and the number of panicles of the transgenic plants
      and yields of the F2 hybrid rice, were analysed. Quality indexes of the
      transgenic plants and of the F2 hybrid seeds were analysed. Our researches
      results indicate that hybrid female and hybrid descendant edibility could be
      improved via the introduction of the anti-Waxy gene, but the grain yields of the
      reserve seeds via self-pollination of the transgenic photo-thermo sensitive genic
      sterile lines and of the hybrid rice were not affected. 

PMID- 23853509
TI  - QTL analysis for early-maturing traits in cotton using two upland cotton
      (Gossypium hirsutum L.) crosses.
AB  - Making use of the markers linked closely to QTL for early-maturing traits for MAS
      (Marker-assisted selection) is an effective method for the simultaneous
      improvement of early maturity and other properties in cotton. In this study, two
      F2 populations and their F2:3 families were generated from the two upland cotton
      (Gossypium hirsutum L.) crosses, Baimian2 * TM-1 and Baimian2 * CIR12. QTL for
      early-maturing traits were analyzed using F2:3 families. A total of 54 QTL (31
      suggestive and 23 significant) were detected. Fourteen significant QTL had the
      LOD scores not only > 3 but also exceeding permutation threshold. At least four
      common QTL, qBP-17 for bud period (BP), qGP-17a/qGP-17b (qGP-17) for growth
      period (GP), qYPBF-17a/qYPBF-17b (qYPBF-17) for yield percentage before frost
      (YPBF) and qHFFBN-17 for height of first fruiting branch node (HFFBN), were found
      in both populations. These common QTL should be reliable and could be used for
      MAS to facilitate early maturity. The common QTL, qBP-17, had a LOD score not
      only > 3 but also exceeding permutation threshold, explaining 12.6% of the
      phenotypic variation. This QTL should be considered preferentially in MAS. Early
      maturing traits of cotton are primarily controlled by dominant and over-dominant
      effects. 

PMID- 23853510
TI  - Genetic analysis and fine mapping of a semi-dwarf gene in a centromeric region in
      rice (Oryza sativa L.).
AB  - Superior plant architecture is a key means of enhancing yield potential in high
      yielding varieties. A newly identified recessive gene, named sd-c, controls plant
      height and tiller number. Genetic analysis of an F2 population from a cross
      between the semi-dwarf mutant and japonica cv. Houshengheng showed that the sd-c
      locus was flanked by SSR markers RM27877 and RM277 on chromosome 12. Thirty nine
      InDel markers were developed in the region and the sd-c gene was further mapped
      to a 1 cM centromeric region between InDel markers C11 and C12. These sequenced
      markers can be used to distinguish wild type and mutants and thus can be used in
      marker-assisted selection. The sd-c mutant decreases culm length by about 26% and
      doubles the tiller number without changing seed weight. Until now only sd-1 has
      been used in indica rice breeding programs. The sd-c mutant seems to have no
      undesirable pleiotropic effects and is therefore a potential genetic resource for
      breeding semi-dwarf indica rice cultivars. 

PMID- 23853512
TI  - De novo assembly of the complete organelle genome sequences of azuki bean (Vigna
      angularis) using next-generation sequencers.
AB  - Since chloroplasts and mitochondria are maternally inherited and have unique
      features in evolution, DNA sequences of those organelle genomes have been broadly
      used in phylogenetic studies. Thanks to recent progress in next-generation
      sequencer (NGS) technology, whole-genome sequencing can be easily performed.
      Here, using NGS data generated by Roche GS Titanium and Illumina Hiseq 2000, we
      performed a hybrid assembly of organelle genome sequences of Vigna angularis
      (azuki bean). Both the mitochondrial genome (mtDNA) and the chloroplast genome
      (cpDNA) of V. angularis have very similar size and gene content to those of V.
      radiata (mungbean). However, in structure, mtDNA sequences have undergone many
      recombination events after divergence from the common ancestor of V. angularis
      and V. radiata, whereas cpDNAs are almost identical between the two. The
      stability of cpDNAs and the variability of mtDNAs was further confirmed by
      comparative analysis of Vigna organelles with model plants Lotus japonicus and
      Arabidopsis thaliana. 

PMID- 23853511
TI  - Characterization and mapping of novel chlorophyll deficient mutant genes in durum
      wheat.
AB  - The yellow-green leaf mutant has a non-lethal chlorophyll-deficient mutation that
      can be exploited in photosynthesis and plant development research. A novel yellow
      green mutant derived from Triticum durum var. Cappelli displays a yellow-green
      leaf color from the seedling stage to the mature stage. Examination of the mutant
      chloroplasts with transmission electron microscopy revealed that the shape of
      chloroplast changed, grana stacks in the stroma were highly variable in size and
      disorganized. The pigment content, including chlorophyll a, chlorophyll b, total
      chlorophyll and carotene, was decreased in the mutant. In contrast, the chla/chlb
      ratio of the mutants was increased in comparison with the normal green leaves. We
      also found a reduction in the photosynthetic rate, fluorescence kinetic
      parameters and yield-related agronomic traits of the mutant. A genetic analysis
      revealed that two nuclear recessive genes controlled the expression of this
      trait. The genes were designated ygld1 and ygld2. Two molecular markers co
      segregated with these genes. ygld 1 co-segregated with the SSR marker wmc110 on
      chromosome 5AL and ygld 2 co-segregated with the SSR marker wmc28 on chromosome
      5BL. These results will contribute to the gene cloning and the understanding of
      the mechanisms underlying chlorophyll metabolism and chloroplast development in
      wheat. 

PMID- 23853513
TI  - Diversification and genetic differentiation of cultivated melon inferred from
      sequence polymorphism in the chloroplast genome.
AB  - Molecular analysis encouraged discovery of genetic diversity and relationships of
      cultivated melon (Cucumis melo L.). We sequenced nine inter- and intra-genic
      regions of the chloroplast genome, about 5500 bp, using 60 melon accessions and
      six reference accessions of wild species of Cucumis to show intra-specific
      variation of the chloroplast genome. Sequence polymorphisms were detected among
      melon accessions and other Cucumis species, indicating intra-specific
      diversification of the chloroplast genome. Melon accessions were classified into
      three subclusters by cytoplasm type and then into 12 subgroups. Geographical
      origin and seed size also differed between the three subclusters. Subcluster Ia
      contained small-seed melon from Southern Africa and South and East Asia and
      subcluster Ib mainly consisted of large-seed melon from northern Africa, Europe
      and USA. Melon accessions of subcluster Ic were only found in West, Central and
      Southern Africa. Our results indicated that European melon groups and Asian melon
      groups diversified independently and shared the same maternal lineage with
      northern African large-seed melon and Southern African small-seed melon,
      respectively. Cultivated melon of subcluster Ic may have been domesticated
      independently in Africa. The presence of 11 cytoplasm types in Africa strongly
      supported African origin of cultivated melon and indicated the importance of
      germplasm from Africa. 

PMID- 23853514
TI  - Genetical and morphological characterization of cold tolerance at fertilization
      stage in rice.
AB  - Cold temperature during the reproductive phase leads to seed sterility, which
      reduces yield and decreases the grain quality of rice. The fertilization stage,
      ranging from pollen maturation to the completion of fertilization, is sensitive
      to unsuitable temperature. Improving cold tolerance at the fertilization stage
      (CTF) is an important objective of rice breeding program in cold temperature
      areas. In this study, we characterized fertilization behavior under cold
      temperature to define the phenotype of CTF and identified quantitative trait loci
      (QTLs) for CTF. A wide variation in CTF levels has been identified among local
      cultivars in Hokkaido, which is one of the most northern regions for rice
      cultivation in the world. Clear varietal differences in pollen germination, and
      pollen tube elongation due to cold temperature have been observed. These
      differences may confer a degree of CTF among this population. We conducted QTL
      analysis for CTF using 120 backcrossed inbred lines derived from a cross between
      Eikei88223 (vigorous CTF) and Suisei (very weak CTF). Three QTLs for CTF were
      identified. A clear effect by QTL, qCTF7, for increasing the level of CTF was
      validated using advanced progeny. These results will facilitate marker-assist
      selection for desirable QTLs for CTF in rice breeding program. 

PMID- 23853515
TI  - Accumulation of gamma-aminobutyrate (GABA) caused by heat-drying and expression
      of related genes in immature vegetable soybean (edamame).
AB  - We studied the effects of drying of immature seeds of vegetable soybean (Glycine
      max L. Merrill) on the accumulation of gamma-aminobutyrate (GABA) in the seeds.
      GABA accumulated after heat-drying, with the maximum at 40 degrees C. The GABA
      content (447.5 mg/100 g DW) increased to more than 5 times the value in untreated
      seeds (79.6 mg/100 g DW). In contrast, the glutamate content decreased rapidly to
      1/3 the level in the untreated seeds. The GABA content increased early in the
      heat-drying treatment: after 30 min, it had increased to 1.5 times the value in
      the untreated seeds. GABA did not accumulate in the vacuum-drying treatment.
      Among genes related to the GABA shunt, the gene for glutamate decarboxylase (EC
      4.1.1.15), which catalyzes the decarboxylation of glutamate to produce GABA,
      showed relatively high expression, decreasing to only 70% of the value in
      untreated seeds even after 4 h of treatment. In contrast, expression of the genes
      for two catabolic mitochondrial enzymes, GABA transaminase (GABA-T; EC 2.6.1.19)
      and succinate semialdehyde dehydrogenase (SSADH; EC 1.2.1.16), decreased rapidly
      during heat-drying. These results suggest that the accumulated GABA was not
      metabolized rapidly by GABA-T and SSADH and therefore remained at high levels. 

PMID- 23853516
TI  - Use of image analysis to estimate anthocyanin and UV-excited fluorescent phenolic
      compound levels in strawberry fruit.
AB  - Strawberry is rich in anthocyanins, which are responsible for the red color, and
      contains several colorless phenolic compounds. Among the colorless phenolic
      compounds, some, such as hydroxycinammic acid derivatives, emit blue-green
      fluorescence when excited with ultraviolet (UV) light. Here, we investigated the
      effectiveness of image analyses for estimating the levels of anthocyanins and UV
      excited fluorescent phenolic compounds in fruit. The fruit skin and cut surface
      of 12 cultivars were photographed under visible and UV light conditions; colors
      were evaluated based on the color components of images. The levels of
      anthocyanins and UV-excited fluorescent compounds in each fruit were also
      evaluated by spectrophotometric and high performance liquid chromatography (HPLC)
      analyses, respectively and relationships between these levels and the image data
      were investigated. Red depth of the fruits differed greatly among the cultivars
      and anthocyanin content was well estimated based on the color values of the cut
      surface images. Strong UV-excited fluorescence was observed on the cut surfaces
      of several cultivars, and the grayscale values of the UV-excited fluorescence
      images were markedly correlated with the levels of those fluorescent compounds as
      evaluated by HPLC analysis. These results indicate that image analyses can select
      promising genotypes rich in anthocyanins and fluorescent phenolic compounds. 

PMID- 23853517
TI  - Construction of a chromosome-assigned, sequence-tagged linkage map for the
      radish, Raphanus sativus L. and QTL analysis of morphological traits.
AB  - The radish displays great morphological variation but the genetic factors
      underlying this variability are mostly unknown. To identify quantitative trait
      loci (QTLs) controlling radish morphological traits, we cultivated 94 F4 and F5
      recombinant inbred lines derived from a cross between the rat-tail radish and the
      Japanese radish cultivar 'Harufuku' inbred lines. Eight morphological traits
      (ovule and seed numbers per silique, plant shape, pubescence and root formation)
      were measured for investigation. We constructed a map composed of 322 markers
      with a total length of 673.6 cM. The linkage groups were assigned to the radish
      chromosomes using disomic rape-radish chromosome-addition lines. On the map,
      eight and 10 QTLs were identified in 2008 and 2009, respectively. The chromosome
      linkage group correspondence, the sequence-specific markers and the QTLs detected
      here will provide useful information for further genetic studies and for
      selection during radish breeding programs. 

PMID- 23853518
TI  - Complexity of indica-japonica varietal differentiation in Bangladesh rice
      landraces revealed by microsatellite markers.
AB  - To understand the genetic diversity and indica-japonica differentiation in
      Bangladesh rice varieties, a total of 151 accessions of rice varieties mostly
      Bangladesh traditional varieties including Aus, Boro, broadcast Aman, transplant
      Aman and Rayada varietal groups were genotyped using 47 rice nuclear SSRs. As a
      result, three distinct groups were detected by cluster analysis, corresponding to
      indica, Aus and japonica rice. Among deepwater rice varieties analyzed some
      having particular morphological features that mainly corresponded to the japonica
      varietal group. Some small seeded and aromatic varieties from Bangladesh also
      corresponded to the japonica varietal group. This research for the first time
      establishes that the japonica varietal group is a prominent component of
      traditional varieties in Bangladesh, particularly in deepwater areas. 

PMID- 23853519
TI  - Breeding of new rice cultivar 'Tohoku 194' with 'Sasanishiki'-type good eating
      quality of cooked rice.
AB  - Cooked rice of 'Sasanishiki' is soft and not as sticky as those of Japanese
      leading cultivars 'Koshihikari' and 'Hitomebore'. As a method for efficient
      selection of a breeding line having a good eating quality like that of
      'Sasanishiki', the use of physical properties of cooked rice and cooking quality
      was examined. There were differences of physical properties of the surface layer,
      starch-iodine blue value per solid substance weight in cooking water and volume
      expansion of cooked rice between 'Sasanishiki' and 'Hitomebore', these properties
      being considered to be usable for the selection of breeding lines. Using these
      traits as selection targets, one line, named 'Tohoku 194', which has eating
      quality highly similar to that of 'Sasanishiki' and cold tolerance derived from
      'Hitomebore', was selected from progeny of a cross between 'Sasanishiki' and
      'Hitomebore'. An application for registration as a new variety has been submitted
      for 'Tohoku 194' under the Japanese Plant Variety Protection Act, and is expected
      to become a recommended cultivar in Miyagi Prefecture. 'Tohoku 194' may fulfill
      various demands of consumers and companies in the food industry. 

PMID- 23853520
TI  - Initial epidemic area is strongly associated with the yearly extent of soybean
      rust spread in North America.
AB  - Hosts of soybean rust (Phakopsora pachyrhizi) are sensitive to low temperatures,
      limiting this obligate parasite in the United States to overwintering sites in a
      restricted area along the Gulf Coast. This temperature sensitivity of soybean
      rust hosts allowed us to study spatial spread of epidemic invasions over similar
      territory for seven sequential years, 2005-2011. The epidemic front expanded
      slowly from early April through July, with the majority of expansion occurring
      from August through November. There was a 7.4-fold range of final epidemic extent
      (0.4 to 3.0 million km2) from the year of smallest final disease extent (2011) to
      that of the largest (2007). The final epidemic area of each year was regressed
      against epidemic areas recorded at one-week intervals to determine the
      association of final epidemic extent with current epidemic extent. Coefficients
      of determination for these regressions varied between 0.44 to 0.62 during April
      and May. The correlation coefficients varied between 0.70 and 0.96 from early
      June through October, and then increased monotonically to 1.0 by year's end.
      Thus, the spatial extent of disease when the epidemics began rapid expansion may
      have been a crucial contributor to subsequent spread of soybean rust. Our
      analyses used presence/absence data at the county level to evaluate the spread of
      the epidemic front only; the subsequent local intensification of disease could be
      strongly influenced by other factors, including weather.

PMID- 23853521
TI  - Synthesis and catalytic properties of a series of cobalt porphyrins as cytochrome
      P450 model: the effect of substituents on the catalytic activity.
AB  - A series of cobalt porphyrins derived from hemin was prepared as cytochrome P450
      models. Effects of substituents at the cobalt deuteroporphyrin-propionate side
      chains are investigated in oxidation of toluene with air to benzaldehyde and
      benzyl alcohol without the use of solvent and sacrificial co-reductant. The
      catalytic activity of cobalt porphyrins depends on the type of substituents. When
      the electron-withdrawing groups like -Cl, -Br, were introduced into the double
      propionate side chains, they can increase the catalyst stability and selectivity
      to benzaldehyde. In comparison with these electron-withdrawing groups, the
      electron-donor groups, such as -CH3, -S-S- and -NH2 groups, can improve their
      catalytic activities. Moreover, the electron-donor group containing an unpaired
      electron (such as -S-S-, -NH2) is benefit for improving its catalytic efficiency
      and promoting the electron delivery. It can be concluded that the double
      propionate side chains in the deuteroporphyrin complex may participate in
      oxidation process and effect electron transfer from the high-valent
      metalloporphyrin species to the substrate.

PMID- 23853523
TI  - Virus-host and CRISPR dynamics in Archaea-dominated hypersaline Lake Tyrrell,
      Victoria, Australia.
AB  - The study of natural archaeal assemblages requires community context, namely, a
      concurrent assessment of the dynamics of archaeal, bacterial, and viral
      populations. Here, we use filter size-resolved metagenomic analyses to report the
      dynamics of 101 archaeal and bacterial OTUs and 140 viral populations across 17
      samples collected over different timescales from 2007-2010 from Australian
      hypersaline Lake Tyrrell (LT). All samples were dominated by Archaea (75-95%).
      Archaeal, bacterial, and viral populations were found to be dynamic on timescales
      of months to years, and different viral assemblages were present in planktonic,
      relative to host-associated (active and provirus) size fractions. Analyses of
      clustered regularly interspaced short palindromic repeat (CRISPR) regions
      indicate that both rare and abundant viruses were targeted, primarily by lower
      abundance hosts. Although very few spacers had hits to the NCBI nr database or to
      the 140 LT viral populations, 21% had hits to unassembled LT viral concentrate
      reads. This suggests local adaptation to LT-specific viruses and/or undersampling
      of haloviral assemblages in public databases, along with successful CRISPR
      mediated maintenance of viral populations at abundances low enough to preclude
      genomic assembly. This is the first metagenomic report evaluating widespread
      archaeal dynamics at the population level on short timescales in a hypersaline
      system. 

PMID- 23853524
TI  - Integrating a CAM Therapeutic Strategy for Hypertension.
AB  - Traditional approaches used to manage the complexities of hypertension (HTN) have
      achieved modest success. Most persons with HTN in the United States have blood
      pressure that is uncontrolled or inadequately controlled on medications, or they
      are unaware that they even have HTN. Because so many US adults with uncontrolled
      HTN are at risk for developing heart disease and stroke, an innovative
      therapeutic approach is needed. One such approach, a complementary and
      alternative medicine strategy called IZI LLC sponsors Self I-Dentity through
      Ho'oponopono(r) (SITH(r)), shows promise in the management of HTN and other
      chronic health conditions. The goal of this article is to describe the SITH(r)
      process and how this therapeutic strategy can be used in practice.

PMID- 23853525
TI  - Symptoms Experienced by Heart Failure Patients in Hospice Care.

PMID- 23853526
TI  - Settings of Care within Hospice: New Options and Questions about Dying "At Home"
AB  - Although place of death has been routinely studied in end-of-life (EOL) care,
      more analysis on place of death within hospice is needed because of the recent,
      dramatic rise in the number of hospice patients dying in inpatient settings.
      Using a case study to illustrate the complexity of determinants of place of death
      within hospice, this article highlights important known factors and elucidate
      gaps for further research. Individual and system level factors, sociocultural
      meanings, caregiving and preferences are shown to have important implications.
      Additionally, the unique components of home hospice, inpatient hospice and
      transitions between these settings may have a fundamental role in the future of
      quality EOL care. Further research on determinants of hospice settings of care is
      essential to the care of older adults at the end of life.

PMID- 23853527
TI  - "Everything They Were Discussing, We Were Already Doing": Hospice Heart Failure
      Caregivers Reflect on a Palliative Caregiving Intervention.

PMID- 23853528
TI  - Removal of lead (II) ions from aqueous solutions onto activated carbon derived
      from waste biomass.
AB  - The removal of lead (II) ions from aqueous solutions was carried out using an
      activated carbon prepared from a waste biomass. The effects of various parameters
      such as pH, contact time, initial concentration of lead (II) ions, and
      temperature on the adsorption process were investigated. Energy Dispersive X-Ray
      Spectroscopy (EDS) analysis after adsorption reveals the accumulation of lead
      (II) ions onto activated carbon. The Langmuir and Freundlich isotherm models were
      applied to analyze equilibrium data. The maximum monolayer adsorption capacity of
      activated carbon was found to be 476.2 mg g-1. The kinetic data were evaluated
      and the pseudo-second-order equation provided the best correlation. Thermodynamic
      parameters suggest that the adsorption process is endothermic and spontaneous.

PMID- 23853529
TI  - The use of START/STOPP criteria for elderly patients in primary care.
AB  - AIM: Our aim was to detect older patients who were prescribed inappropriate drugs
      according to START/STOPP criteria in primary care. MATERIALS AND METHOD: Patients
      aged over 65, admitted to health center no. 5 in Afyon, were included. The files
      of the subjects were surveyed retrospectively for the final one year in the
      digital environment, using the Family Medicine Information System. The files
      surveyed allowed us to list the drugs they used in the past year and to detect
      inappropriate drug use. RESULTS: The number of patients that took part in this
      study was 325 (average age: 73.23 +/- 6.44 years). We found that, among these
      participants, 48 patients (14.8%) were using drugs inappropriately according to
      STOPP criteria. CONCLUSION: Further focus on avoiding inappropriate drug use will
      allow clinicians and other health professionals to reduce side effects and other
      complications. In patients aged over 65, there is a need to attach particular
      importance to inappropriate drug use, drug interactions, and avoidance of side
      effects.

PMID- 23853530
TI  - Dual silencing of Hsp27 and c-FLIP enhances doxazosin-induced apoptosis in PC-3
      prostate cancer cells.
AB  - We evaluated effect of dual gene silencing of Hsp27 and c-FLIP in doxazosin
      induced apoptosis of PC-3 cell. After transfection using Hsp27 and c-FLIP siRNA
      mixture (dual silencing), doxazosin treatment was done at the concentrations of
      1, 10, and 25  MU M. We checked apoptosis of PC-3 cells with and TUNEL staining.
      We also checked interaction between Hsp27 and C-FLIP in the process of apoptosis
      inhibition. Spontaneous apoptotic index was 5% under single gene silencing of
      Hsp27 and c-FLIP and 7% under dual silencing of Hsp27 and c-FLIP. When doxazosin
      treatment was added, apoptotic indices increased in a dose-dependent manner (1,
      10, and 25  MU M): nonsilencing 10, 27, and 52%; Hsp27-silencing: 14, 35, and
      68%; c-FLIP silencing: 21, 46, and 78%; dual silencing: 38, 76, and 92%. While c
      FLIP gene expression decreased in Hsp27- silenced cells, Hsp27 gene expression
      showed markedly decreased pattern in the cells of c-FLIP silencing. The knockout
      of c-FLIP and Hsp27 genes together enhances apoptosis even under 1  MU M, rather
      than low concentration, of doxazosin in PC-3 cells. This finding suggests a new
      strategy of multiple knockout of antiapoptotic and survival factors in the
      treatment of late-stage prostate cancer refractory to conventional therapy. 

PMID- 23853532
TI  - A note on the observational evidence for the existence of event horizons in
      astrophysical black hole candidates.
AB  - Black holes have the peculiar and intriguing property of having an event horizon,
      a one-way membrane causally separating their internal region from the rest of the
      Universe. Today, astrophysical observations provide some evidence for the
      existence of event horizons in astrophysical black hole candidates. In this short
      paper, I compare the constraint we can infer from the nonobservation of
      electromagnetic radiation from the putative surface of these objects with the
      bound coming from the ergoregion instability, pointing out the respective
      assumptions and limitations. 

PMID- 23853531
TI  - Effects of edaravone, a free radical scavenger, on photochemically induced
      cerebral infarction in a rat hemiplegic model.
AB  - Edaravone is a free radical scavenger that protects the adjacent cortex during
      cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a
      photochemically induced infarction with the photosensitive dye, rose bengal, in
      rats. We examined the effects of edaravone on recovery in the model. A total of
      36 adult Wistar rats were used. The right sensorimotor area was irradiated with
      green light with a wavelength of 533 nm (10 mm diameter), and the rose bengal was
      injected intravenously to create an infarction. The edaravone group was injected
      intraperitoneally with edaravone (3 mg/kg), and the control group was injected
      with saline. The recovery process of the hemiplegia was evaluated with the 7-step
      scale of Fenny. The infarcted areas were measured after fixation. The recovery of
      the paralysis in the edaravone-treated group was significantly earlier than that
      in the untreated group. Seven days later, both groups were mostly recovered and
      had scores of 7, and the infarction region was significantly smaller in the
      edaravone-treated group. Edaravone reduced the infarction area and promoted the
      functional recovery of hemiparesis from cerebral thrombosis in a rat model. These
      findings suggest that edaravone treatment would be effective in clinical patients
      recovering from cerebral infarction.

PMID- 23853533
TI  - A review of surface water quality models.
AB  - Surface water quality models can be useful tools to simulate and predict the
      levels, distributions, and risks of chemical pollutants in a given water body.
      The modeling results from these models under different pollution scenarios are
      very important components of environmental impact assessment and can provide a
      basis and technique support for environmental management agencies to make right
      decisions. Whether the model results are right or not can impact the
      reasonability and scientificity of the authorized construct projects and the
      availability of pollution control measures. We reviewed the development of
      surface water quality models at three stages and analyzed the suitability,
      precisions, and methods among different models. Standardization of water quality
      models can help environmental management agencies guarantee the consistency in
      application of water quality models for regulatory purposes. We concluded the
      status of standardization of these models in developed countries and put forward
      available measures for the standardization of these surface water quality models,
      especially in developing countries. 

PMID- 23853534
TI  - A unique finite element modeling of the periodic wave transformation over sloping
      and barred beaches by Beji and Nadaoka's Extended Boussinesq equations.
AB  - This paper presents a numerical model based on one-dimensional Beji and Nadaoka's
      Extended Boussinesq equations for simulation of periodic wave shoaling and its
      decomposition over morphological beaches. A unique Galerkin finite element and
      Adams-Bashforth-Moulton predictor-corrector methods are employed for spatial and
      temporal discretization, respectively. For direct application of linear finite
      element method in spatial discretization, an auxiliary variable is hereby
      introduced, and a particular numerical scheme is offered to rewrite the equations
      in lower-order form. Stability of the suggested numerical method is also
      analyzed. Subsequently, in order to display the ability of the presented model,
      four different test cases are considered. In these test cases, dispersive and
      nonlinearity effects of the periodic waves over sloping beaches and barred
      beaches, which are the common coastal profiles, are investigated. Outputs are
      compared with other existing numerical and experimental data. Finally, it is
      concluded that the current model can be further developed to model any
      morphological development of coastal profiles. 

PMID- 23853535
TI  - Low density solvent-based dispersive liquid-liquid microextraction for the
      determination of synthetic antioxidants in beverages by high-performance liquid
      chromatography.
AB  - A simple and efficient method was established for the determination of synthetic
      antioxidants in beverages by using dispersive liquid-liquid microextraction
      combined with high-performance liquid chromatography with ultraviolet detection.
      Butylated hydroxy toluene, butylated hydroxy anisole, and tert-butylhydroquinone
      were the antioxidants evaluated. Experimental parameters including extraction
      solvent, dispersive solvent, pH of sample solution, salt concentration, and
      extraction time were optimized. Under optimal conditions, the extraction
      recoveries ranged from 53 to 96%. Good linearity was observed by the square of
      correlation coefficients ranging from 0.9975 to 0.9997. The relative standard
      deviations ranged from 1.0 to 5.2% for all of the analytes. Limits of detection
      ranged from 0.85 to 2.73 ng mL(-1). The method was successfully applied for
      determination of synthetic antioxidants in undiluted beverage samples with
      satisfactory recoveries.

PMID- 23853536
TI  - Assessment of spatial variability of heavy metals in Metropolitan Zone of Toluca
      Valley, Mexico, using the biomonitoring technique in mosses and TXRF analysis.
AB  - This study is aimed at assessing atmospheric deposition of heavy metals using the
      epiphytic moss genera Fabronia ciliaris collected from six urban sites in the
      Metropolitan Zone of the Toluca Valley in Mexico. The concentrations of K, Ca,
      Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Rb, Sr, and Pb were determined by total reflection
      X-ray fluorescence technique. Results show that the average metal concentration
      decrease in the following order: Fe (8207 mg/Kg) > Ca (7315 mg/Kg) > K (3842
      mg/Kg) > Ti (387 mg/Kg) > Mn, Zn (191 mg/Kg) > Sr (71 mg/Kg) > Pb (59 mg/Kg) >
      Cu, V (32 mg/Kg) > Cr (24 mg/Kg) > Rb (13 mg/Kg) > Ni (10 mg/Kg). Enrichment
      factors show a high enrichment for Cr, Cu, Zn, and Pb which provides an evidence
      of anthropogenic impact in the industrial and urban areas, mainly due to the
      intense vehicular traffic and the fossil fuel combustion. Monitoring techniques
      in mosses have proved to be a powerful tool for determining the deposition of
      heavy metals coming from diverse point sources of pollution.

PMID- 23853537
TI  - The evaluation of a modified Dufourmentel flap after S-type excision for
      pilonidal sinus disease.
AB  - PURPOSE: The use of an S-type oblique excision with a bilateral gluteus maximus
      advancement flap has recently been described for the surgical treatment of
      sacrococcygeal pilonidal sinus (SPS). Its use in wide lesions has been limited
      due to the need for a full-thickness flap. We describe the use of an S-type
      oblique incision together with the Dufourmentel flap in wide lesions. METHOD:
      Twenty-one patients were treated using a technique including an S-shaped oblique
      excision of the sinus tract and a broad-pedicled full-thickness flap resembling a
      Dufourmentel flap to close the defect. RESULTS: Of the 21 patients, 19 (90.5%)
      were male and 2 (9.5%) were female. Their mean age was 24.0 +/- 6.1 (range 15-36)
      years. The mean follow-up period was 14.0 +/- 5.8 (range 6-23) months. The
      postoperative complication rate was 4.8% (one patient), and recurrence was seen
      in one patient (4.8%). The mean return-to-work time was 13.5 +/- 1.9 (range 10
      18) days. None of the patients reported dissatisfaction with the cosmetic
      results. CONCLUSIONS: This new technique achieved low morbidity and recurrence
      rates. We anticipate that this will become an important technique in the surgical
      treatment of SPS if the observed success is confirmed by randomized prospective
      trials.

PMID- 23853538
TI  - Identification of input nonlinear control autoregressive systems using fractional
      signal processing approach.
AB  - A novel algorithm is developed based on fractional signal processing approach for
      parameter estimation of input nonlinear control autoregressive (INCAR) models.
      The design scheme consists of parameterization of INCAR systems to obtain linear
      in-parameter models and to use fractional least mean square algorithm (FLMS) for
      adaptation of unknown parameter vectors. The performance analyses of the proposed
      scheme are carried out with third-order Volterra least mean square (VLMS) and
      kernel least mean square (KLMS) algorithms based on convergence to the true
      values of INCAR systems. It is found that the proposed FLMS algorithm provides
      most accurate and convergent results than those of VLMS and KLMS under different
      scenarios and by taking the low-to-high signal-to-noise ratio. 

PMID- 23853539
TI  - Adventitious shoot regeneration from leaf explant of dwarf hygro (Hygrophila
      polysperma (Roxb.) T. Anderson).
AB  - Dwarf hygro (Hygrophila polysperma) is an ornamental aquatic plant that changes
      its leaf colours to pinkish in high light. It is listed as a medicinal plant in
      medicinal plant lists of Indian states of West Bengal and Karnataka. It is also
      used as a screening tool for toxicities and a bioindicator to detect and control
      algae. The study reported in vitro adventitious shoot regeneration from leaf
      explants cultured on MS medium containing 0.10-1.60 mg/L Kin/TDZ with or without
      0.10 mg/L IBA and 500 mg/L Amoklavin to eradicate endogenic bacterial
      contamination. Direct adventitious shoot regeneration started within one week
      from both culture mediums followed by late callus induction which was more
      prominent on TDZ containing media compared to Kin containing media. Addition of
      0.10 mg/L IBA with both Kin and TDZ increased shoot regeneration frequency, mean
      number of shoots per explant, and mean shoot length. Maximum number of 16.33 and
      20.55 shoots per explant was obtained on MS medium containing 0.80 + 0.10 mg/L
      Kin-IBA and 0.10 + 0.10 mg/L TDZ-IBA, respectively. Regenerated shoots were
      rooted on MS medium containing 0.20-1.00 mg/L IBA followed by successfull
      acclimatization in aquariums. Regenerated plantlets were also tested in jars
      containing distilled water that showed the pH 6-9 for the best plant growth and
      development.

PMID- 23853540
TI  - Environmental gradient favours functionally diverse macrobenthic community in a
      placer rich tropical bay.
AB  - The present paper examines the functional diversity-environment relation in a
      placer rich tropical bay. Understanding the environmental variables that
      determine the biodiversity pattern will help in the effective conservation plans
      of coastal habitat. However, few studies have been carried out on the
      biodiversity-environment relation from the diverse tropical coastal ecosystem.
      The geographic location of Kalbadevi Bay along the west coast of India provides
      an opportunity to study the functional diversity pattern of macrofauna along an
      environmental gradient. Additionally, the area is also a potential placer mining
      site. Seasonal sampling was carried out for macrofauna and environmental
      variables. Macrofaunal functional diversity showed significant temporal variation
      related to the environmental parameters. The most important environmental
      variables were organic matter and sediment texture. Filter feeders dominated
      during postmonsoon which is a period when the water column is enriched with
      sinking detritus. The deposit feeders which rapidly ingest the settled detritus
      and also transport it to deeper sediment for the subsurface deposit feeders
      dominated during premonsoon. Abundance of carnivores was high during premonsoon,
      a response to increase in food in terms of deposit feeders. The result thus
      indicates that the temporal environmental variation influenced the macrofaunal
      functional diversity pattern in the Kalbadevi Bay. 

PMID- 23853541
TI  - Stacked central configurations for the spatial nine-body problem.
AB  - We show the existence of the twisted stacked central configurations for the 9
      body problem. More precisely, the position vectors x1, x2, x3, x4, and x5 are at
      the vertices of a square pyramid Sigma; the position vectors x6, x7, x8, and x9
      are at the vertices of a square Pi.

PMID- 23853542
TI  - Occurrence and distribution of microcystins in Lake Taihu, China.
AB  - The occurrence and distribution of microcystins were investigated in Lake Taihu,
      the third largest lake in China. An extensive survey, larger and broader in scale
      than previous studies, was conducted in summer 2010. The highest microcystin
      concentration was found at southern part of Taihu, which was newly included in
      this survey. In northern coastal areas, total cellular concentrations of 20 to 44
      MUg/L were observed. In northern offshore waters, levels were up to 4.8 MUg/L.
      Microcystin occurrence was highly correlated with chemical oxygen demand,
      turbidity, and chlorophyll-a. Extracellular/total cellular microcystin (E/T)
      ratios were calculated and compared to other water quality parameters. A higher
      correlation was found using E/T ratios than original microcystin values. These
      results show that algal blooms are having a severe impact on Lake Taihu, and
      further and extensive monitoring and research are required to suppress blooms
      effectively. 

PMID- 23853543
TI  - Bullying within the forestry organizations of Turkey.
AB  - Today, many studies are conducted in order to determine bullying behaviors and to
      resolve conflicts with the purpose of increasing and maintaining organizational
      success in developed countries. According to these studies, bullying cases are
      more common in public institutions when compared to other sectors. In public
      institutions, bullying generally occurs when successful workers are discouraged
      and/or harassed by their managers, thus leaving them feeling distressed and
      dissatisfied with their jobs. The present study examines whether forest engineers
      working in the seven geographical regions of Turkey are exposed to bullying
      behaviors, the level of any bullying, and whether there are any regional
      differences (N = 835). Through statistical analysis, a significant relationship
      was determined between bullying and demographic characteristics. The results of
      the present study were evaluated along with the results of other studies, and
      some suggestions were made in order to prevent bullying behaviors in forestry
      organizations. 

PMID- 23853544
TI  - Robust adaptive control for a class of uncertain nonlinear systems with time
      varying delay.
AB  - We present adaptive neural control design for a class of perturbed nonlinear MIMO
      time-varying delay systems in a block-triangular form. Based on a neural
      controller, it is obtained by constructing a quadratic-type Lyapunov-Krasovskii
      functional, which efficiently avoids the controller singularity. The proposed
      control guarantees that all closed-loop signals remain bounded, while the output
      tracking error dynamics converge to a neighborhood of the desired trajectories.
      The simulation results demonstrate the effectiveness of the proposed control
      scheme. 

PMID- 23853545
TI  - NKT cell-TCR expression activates conventional T cells in vivo, but is largely
      dispensable for mature NKT cell biology.
AB  - Natural killer T (NKT) cell development depends on recognition of self
      glycolipids via their semi-invariant Valpha14i-TCR. However, to what extent TCR
      mediated signals determine identity and function of mature NKT cells remains
      incompletely understood. To address this issue, we developed a mouse strain
      allowing conditional Valpha14i-TCR expression from within the endogenous Tcralpha
      locus. We demonstrate that naive T cells are activated upon replacement of their
      endogenous TCR repertoire with Valpha14i-restricted TCRs, but they do not
      differentiate into NKT cells. On the other hand, induced TCR ablation on mature
      NKT cells did not affect their lineage identity, homeostasis, or innate rapid
      cytokine secretion abilities. We therefore propose that peripheral NKT cells
      become unresponsive to and thus are independent of their autoreactive TCR. 

PMID- 23853546
TI  - Transdifferentiation of fast skeletal muscle into functional endothelium in vivo
      by transcription factor Etv2.
AB  - Etsrp/Etv2 (Etv2) is an evolutionarily conserved master regulator of vascular
      development in vertebrates. Etv2 deficiency prevents the proper specification of
      the endothelial cell lineage, while its overexpression causes expansion of the
      endothelial cell lineage in the early embryo or in embryonic stem cells. We
      hypothesized that Etv2 alone is capable of transdifferentiating later somatic
      cells into endothelial cells. Using heat shock inducible Etv2 transgenic
      zebrafish, we demonstrate that Etv2 expression alone is sufficient to
      transdifferentiate fast skeletal muscle cells into functional blood vessels.
      Following heat treatment, fast skeletal muscle cells turn on vascular genes and
      repress muscle genes. Time-lapse imaging clearly shows that muscle cells turn on
      vascular gene expression, undergo dramatic morphological changes, and integrate
      into the existing vascular network. Lineage tracing and immunostaining confirm
      that fast skeletal muscle cells are the source of these newly generated vessels.
      Microangiography and observed blood flow demonstrated that this new vasculature
      is capable of supporting circulation. Using pharmacological, transgenic, and
      morpholino approaches, we further establish that the canonical Wnt pathway is
      important for induction of the transdifferentiation process, whereas the VEGF
      pathway provides a maturation signal for the endothelial fate. Additionally,
      overexpression of Etv2 in mammalian myoblast cells, but not in other cell types
      examined, induced expression of vascular genes. We have demonstrated in zebrafish
      that expression of Etv2 alone is sufficient to transdifferentiate fast skeletal
      muscle into functional endothelial cells in vivo. Given the evolutionarily
      conserved function of this transcription factor and the responsiveness of
      mammalian myoblasts to Etv2, it is likely that mammalian muscle cells will
      respond similarly. 

PMID- 23853548
TI  - Watching genes loop the loop.

PMID- 23853547
TI  - Transcription-factor-mediated DNA looping probed by high-resolution, single
      molecule imaging in live E. coli cells.
AB  - DNA looping mediated by transcription factors plays critical roles in prokaryotic
      gene regulation. The "genetic switch" of bacteriophage lambda determines whether
      a prophage stays incorporated in the E. coli chromosome or enters the lytic cycle
      of phage propagation and cell lysis. Past studies have shown that long-range DNA
      interactions between the operator sequences O(R) and O(L) (separated by 2.3 kb),
      mediated by the lambda repressor CI (accession number P03034), play key roles in
      regulating the lambda switch. In vitro, it was demonstrated that DNA segments
      harboring the operator sequences formed loops in the presence of CI, but CI
      mediated DNA looping has not been directly visualized in vivo, hindering a deep
      understanding of the corresponding dynamics in realistic cellular environments.
      We report a high-resolution, single-molecule imaging method to probe CI-mediated
      DNA looping in live E. coli cells. We labeled two DNA loci with differently
      colored fluorescent fusion proteins and tracked their separations in real time
      with ~40 nm accuracy, enabling the first direct analysis of transcription-factor
      mediated DNA looping in live cells. Combining looping measurements with
      measurements of CI expression levels in different operator mutants, we show
      quantitatively that DNA looping activates transcription and enhances repression.
      Further, we estimated the upper bound of the rate of conformational change from
      the unlooped to the looped state, and discuss how chromosome compaction may
      impact looping kinetics. Our results provide insights into transcription-factor
      mediated DNA looping in a variety of operator and CI mutant backgrounds in vivo,
      and our methodology can be applied to a broad range of questions regarding
      chromosome conformations in prokaryotes and higher organisms.

PMID- 23853549
TI  - More paths to PI3Kgamma.

PMID- 23853551
TI  - Targeting asymptomatic malaria infections: active surveillance in control and
      elimination.

PMID- 23853552
TI  - The effect of intermittent antenatal iron supplementation on maternal and infant
      outcomes in rural Viet Nam: a cluster randomised trial.
AB  - BACKGROUND: Anemia affects over 500 million women, and in pregnancy is associated
      with impaired maternal and infant outcomes. Intermittent antenatal iron
      supplementation is an attractive alternative to daily dosing; however, the impact
      of this strategy on infant outcomes remains unclear. We compared the effect of
      intermittent antenatal iron supplementation with daily iron supplementation on
      maternal and infant outcomes in rural Viet Nam. METHODS AND FINDINGS: This
      cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258
      pregnant women (< 16 wk gestation) in 104 communes were assigned to daily iron
      folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN)
      supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g
      (standard deviation 416). There was no difference in the birth weights of infants
      of women receiving twice weekly IFA compared to daily IFA (mean difference [MD]
      28 g; 95% CI -22 to 78), or twice weekly MMN compared to daily IFA (MD -36.8 g;
      95% CI -82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women
      receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95%
      CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA
      (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in
      hemoglobin levels. Infants of mothers who received twice weekly IFA had higher
      cognitive scores at 6 mo of age compared to those who received daily IFA (MD
      1.89; 95% CI 0.23 to 3.56). CONCLUSIONS: Twice weekly antenatal IFA or MMN did
      not produce a clinically important difference in birth weight, when compared to
      daily IFA supplementation. The significant improvement in infant cognitive
      outcomes at 6 mo of age following twice weekly antenatal IFA requires further
      exploration, and provides additional support for the use of intermittent, rather
      than daily, antenatal IFA in populations with low rates of iron deficiency. TRIAL
      REGISTRATION: Australia New Zealand Clinical Trials Registry 12610000944033.

PMID- 23853553
TI  - Bigotry and oppressive laws in Africa drive HIV in men who have sex with men.

PMID- 23853554
TI  - Prevalence of consensual male-male sex and sexual violence, and associations with
      HIV in South Africa: a population-based cross-sectional study.
AB  - BACKGROUND: In sub-Saharan Africa the population prevalence of men who have sex
      with men (MSM) is unknown, as is the population prevalence of male-on-male sexual
      violence, and whether male-on-male sexual violence may relate to HIV risk. This
      paper describes lifetime prevalence of consensual male-male sexual behavior and
      male-on-male sexual violence (victimization and perpetration) in two South
      African provinces, socio-demographic factors associated with these experiences,
      and associations with HIV serostatus. METHODS AND FINDINGS: In a cross-sectional
      study conducted in 2008, men aged 18-49 y from randomly selected households in
      the Eastern Cape and KwaZulu-Natal provinces provided anonymous survey data and
      dried blood spots for HIV serostatus assessment. Interviews were completed in
      1,737 of 2,298 (75.6%) of enumerated and eligible households. From these
      households, 1,705 men (97.1%) provided data on lifetime history of same-sex
      experiences, and 1,220 (70.2%) also provided dried blood spots for HIV testing.
      5.4% (n = 92) of participants reported a lifetime history of any consensual
      sexual activity with another man; 9.6% (n = 164) reported any sexual
      victimization by a man, and 3.0% (n = 51) reported perpetrating sexual violence
      against another man. 85.0% (n = 79) of men with a history of consensual sex with
      men reported having a current female partner, and 27.7% (n = 26) reported having
      a current male partner. Of the latter, 80.6% (n = 21/26) also reported having a
      female partner. Men reporting a history of consensual male-male sexual behavior
      are more likely to have been a victim of male-on-male sexual violence (adjusted
      odds ratio [aOR] = 7.24; 95% CI 4.26-12.3), and to have perpetrated sexual
      violence against another man (aOR = 3.10; 95% CI 1.22-7.90). Men reporting
      consensual oral/anal sex with a man were more likely to be HIV+ than men with no
      such history (aOR = 3.11; 95% CI 1.24-7.80). Men who had raped a man were more
      likely to be HIV+ than non-perpetrators (aOR = 3.58; 95% CI 1.17-10.9).
      CONCLUSIONS: In this sample, one in 20 men (5.4%) reported lifetime consensual
      sexual contact with a man, while about one in ten (9.6%) reported experience of
      male-on-male sexual violence victimization. Men who reported having had sex with
      men were more likely to be HIV+, as were men who reported perpetrating sexual
      violence towards other men. Whilst there was no direct measure of male-female
      concurrency (having overlapping sexual relationships with men and women), the
      data suggest that this may have been common. These findings suggest that HIV
      prevention messages regarding male-male sex in South Africa should be
      mainstreamed with prevention messages for the general population, and sexual
      health interventions and HIV prevention interventions for South African men
      should explicitly address male-on-male sexual violence.

PMID- 23853555
TI  - The effectiveness of light/dark exposure to treat insomnia in female nurses
      undertaking shift work during the evening/night shift.
AB  - STUDY OBJECTIVES: The present study investigated whether bright light exposure
      during the first half of the evening/night shift combined with light attenuation
      in the morning is effective in improving sleep problems in nurses undertaking
      rotating shift work who suffer from clinical insomnia. METHODS: This was a
      prospective, randomized control study. The Insomnia Severity Index (ISI) and the
      Hospital Anxiety Depression Scale (HADS) were used to evaluate insomnia and
      anxiety/depression severity, respectively. Female hospital nurses on rotating
      shifts during the evening or night shift with an ISI score > 14 were enrolled.
      Subjects in the treatment group (n = 46) were exposed to bright light at 7,000
      10,000 lux for >= 30 minutes. Exposure was continued for at least 10 days during
      2 weeks, and the subjects avoided daytime outdoor sun exposure after work by
      wearing dark sunglasses. Subjects in the control group (n = 46) were not exposed
      to bright light, but also wore sunglasses after work. Statistical analyses were
      performed to examine group differences and differences across treatments.
      RESULTS: After treatment, the treatment group showed significant improvements in
      the ISI score and the HADS total and subscale scores as compared with pre
      treatment. The ISI, HADS, and subscales of the HADS scores were significantly
      improved across treatments in the treatment group as compared with the control
      group. CONCLUSIONS: The design of this study is easy to put into practice in the
      real world. This is the first study to document that a higher intensity and
      briefer duration of bright light exposure during the first half of the
      evening/night shift with a daytime darkness procedure performed in rotating shift
      work female nurses suffering from clinical insomnia could improve their insomnia,
      anxiety, and depression severity.

PMID- 23853556
TI  - Bright light improves sleep and psychological health in shift working nurses.

PMID- 23853557
TI  - Serum brain-derived neurotrophic factor levels are associated with dyssomnia in
      females, but not males, among Japanese workers.
AB  - STUDY OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is a member of the
      neurotrophin family of growth factors that promote the growth and survival of
      neurons. Recent evidence suggests that BDNF is a sleep regulatory substance that
      contributes to sleep behavior. However, no studies have examined the association
      between the serum BDNF levels and dyssomnia. The present study was conducted to
      clarify the association between the serum BDNF levels and dyssomnia. METHODS: A
      total of 344 workers (age: 40.1 +/- 10.5 years, male: 204, female: 140) were
      included in the study. The serum BDNF levels were categorized into tertiles
      according to sex. RESULTS: The prevalence of dyssomnia was 35.1% in males and
      30.0% in females. In the females, the BDNF levels were found to be negatively
      associated with dyssomnia after adjusting for age, body mass index, hypertension,
      dyslipidemia, hyperglycemia, depression, smoking, alcohol intake, and regular
      exercise. Compared with the females in the high BDNF group, the multivariate odds
      ratio (95% CI) of dyssomnia was 2.08 (0.62-6.98) in females in the moderate BDNF
      group and 8.41 (2.05-27.14) in females in the low BDNF group. No such
      relationships were found in the males. CONCLUSIONS: The serum BDNF levels are
      associated with dyssomnia in Japanese female, but not male, workers.

PMID- 23853558
TI  - Identification of insomnia in a sleep center population using electronic health
      data sources and the insomnia severity index.
AB  - STUDY OBJECTIVES: To assess the validity and efficacy of using electronic health
      data to identify a physician diagnosis of insomnia in a population of patients
      referred for testing at a tertiary sleep center. METHODS: Retrospective cohort
      study in a tertiary sleep center in Calgary, Alberta, Canada. Cohort consisted of
      1,207 patients referred for sleep diagnostic testing and/or assessment by a sleep
      physician. Two sleep physicians independently assigned each patient a primary
      sleep diagnosis. Univariate logistic regression was used to identify variables
      that were predictive for insomnia from online questionnaire and diagnostic
      testing data. Diagnostic algorithms derived from these predictors and from the
      Insomnia Severity Index were evaluated against physician diagnosis as a reference
      standard. RESULTS: The combination of self-reported sleep latency > 20 minutes,
      total sleep time < 6.5 hours per night, the inability to fall asleep after
      waking, BMI < 27 kg/m(2), and Epworth Sleepiness Scale score < 9 had very high
      specificity (99.3%) for diagnosing insomnia; however, sensitivity was poor
      (11.8%). Other algorithms derived from these data had either high sensitivity or
      high specificity. No combination of variables yielded simultaneous high
      sensitivity and specificity. Likewise, the Insomnia Severity Index can be highly
      sensitive or highly specific at identifying insomnia, but not both. CONCLUSIONS:
      Diagnostic algorithms derived from electronic data can provide high specificity
      or high sensitivity for identifying insomnia.

PMID- 23853559
TI  - Middle-of-the-night hypnotic use in a large national health plan.
AB  - STUDY OBJECTIVES: Although difficulty maintaining sleep (DMS) is the most common
      nighttime insomnia symptom among US adults, many FDA-approved hypnotics have
      indications only for sleep onset, stipulating bedtime administration to offset
      residual sedation. Given the well-known self-medication tendencies of insomniacs,
      concern arises that maintenance insomniacs might be prone to self-administer
      their prescribed hypnotics middle-of-the-night (MOTN) after nocturnal awakenings,
      despite little efficacy-safety data supporting such use. However, no US data
      characterize the actual population prevalence or correlates of MOTN hypnotic use.
      METHODS: Telephone interviews assessed patterns of prescription hypnotic use in a
      national sample of 1,927 commercial health plan members (ages 18-64) receiving
      prescription hypnotics within 12 months of study. The Brief Insomnia
      Questionnaire assessed insomnia symptoms. RESULTS: 20.2% of respondents reported
      MOTN hypnotic use, including 9.0% who sometimes used twice-per-night (once at
      bedtime plus once MOTN) and another 11.2% who sometimes used MOTN, but never
      twice-per-night. The remaining 79.8% used exclusively at bedtime. Among exclusive
      MOTN users, only 14.0% used MOTN on the advice of their physician (52.6% of those
      seen by sleep medicine specialists and 42.6% by psychiatrists vs. 5.2% to 13.6%
      seen by other physicians). MOTN use predictors included DMS being the most
      bothersome sleep problem, long duration of hypnotic use, and low frequency of
      DMS. CONCLUSIONS: One-fifth of patients with prescription hypnotics used MOTN,
      only a minority on advice from their physicians. Since significant next-day
      cognitive and psychomotor impairment is documented with off-label MOTN hypnotic
      use, prescribing physicians should question patients about unsupervised MOTN
      dosing.

PMID- 23853560
TI  - Association between sleep duration and the mini-mental score: the Northern
      Manhattan study.
AB  - BACKGROUND: Short and long sleep duration are associated with increased mortality
      and worse global cognitive function, but is unclear if these relations persist
      after accounting for the risk of sleep disordered breathing (SDB). The aim of our
      study is determine the association between short and long sleep duration with
      worse global cognitive function in a racially/ethnically diverse elderly cohort.
      METHODS: We examined sleep hours and global cognitive function cross-sectionally
      within the population-based Northern Manhattan Study cohort. We conducted
      nonparametric and logistic regression to examine associations between continuous,
      short (< 6 h) and long (>= 9 h) sleep hours with performance on the Mini Mental
      State Examination (MMSE). RESULTS: There were 927 stroke-free participants with
      data on self-reported sleep hours and MMSE scores (mean age 75 +/- 9 years, 61%
      women, 68% Hispanics). The median (interquartile range) MMSE was 28 (10-30).
      Sleep hours (centered at 7 h) was associated with worse MMSE (beta = -0.01; SE
      [0.004], p = 0.0113) adjusting for demographics, vascular risk factors,
      medications, and risk for SDB. Reporting long sleep (>= 9 h) compared to 6 to 8 h
      of sleep (reference) was significantly and inversely associated with MMSE
      (adjusted beta = -0.06; SE [0.03], p = 0.012), while reporting short sleep was
      not significantly associated with MMSE performance. Long sleep duration was also
      associated with low MMSE score when dichotomized (adjusted OR: 2.4, 95% CI: 1.1
      5.0). CONCLUSION: In this cross-sectional analysis among an elderly community
      cohort, long sleep duration was associated with worse MMSE performance.

PMID- 23853561
TI  - Characterization of REM sleep without atonia in patients with narcolepsy and
      idiopathic hypersomnia using AASM scoring manual criteria.
AB  - INTRODUCTION: The AASM Manual for the Scoring of Sleep and Associated Events
      (Manual) has provided standardized definitions for tonic and phasic REM sleep
      without atonia (RSWA). This study used Manual criteria to characterize REM sleep
      in patients with narcolepsy and idiopathic hypersomnia (IH). METHODS: A
      retrospective review of PSG data from ICSD-2 defined patients with narcolepsy or
      IH, performed by two board certified sleep medicine physicians. Data compiled
      included REM sleep epochs and the presence in REM sleep of epochs scored as
      sustained muscle activity (tonic), and excessive transient muscle activity
      (phasic) as defined by Manual criteria. RESULTS: PSG data from 8 narcolepsy
      patients (mean age: 27.5 years; age range: 11-55) showed mean +/- standard
      deviation values for: total REM sleep epochs 205 +/- 46.1; RSWA/ phasic epochs
      56.1 +/- 25.4; and RSWA/tonic epochs 15.0 +/- 10.7. PSG data from 8 IH patients
      (mean age: 33.1 years; age range: 20-57) showed mean +/- standard deviation
      values of total REM sleep epochs 163.8 +/- 67.9; RSWA/phasic epochs 6.2 +/- 3.5;
      and RSWA/tonic epochs 0.2 +/- 0.4. Comparison revealed intergroup differences in
      phasic REM sleep (p < 0.01) and tonic REM sleep (p < 0.01) were significantly
      increased in narcoleptics compared to IH. CONCLUSION: Our retrospective analysis
      showed that RSWA phasic activity and RSWA tonic activity are significantly
      increased in patients meeting ICSD-2 criteria for narcolepsy compared to patients
      meeting ICSD-2 criteria for IH. This robust difference, with further validation,
      could be useful as electrophysiological criteria differentiating the two
      disorders and understanding the physiological differences.

PMID- 23853562
TI  - Targeted case finding for OSA within the primary care setting.
AB  - STUDY OBJECTIVES: The aim was to determine the feasibility of using an unattended
      2-channel device to screen for obstructive sleep apnea in a population of high
      risk patients using a targeted, case-finding strategy. The case finding was based
      on the presence of risk factors not symptoms in the studied population. METHODS:
      The study took place from June 2007 to May 2008 in rural and metropolitan
      Queensland and New South Wales. Family doctors were asked to identify patients
      with any of the following: BMI > 30, type 2 diabetes, treated hypertension,
      ischemic heart disease. Participants applied the ApneaLink+O2 at home for a
      single night. The device recorded nasal flow and pulse oximetry. Data were
      analyzed by proprietary software, then checked and reported by either of two
      sleep physicians. RESULTS: 1,157 patients were recruited; mean age 53 +/- 14.6,
      M/F% = 62/38, mean BMI = 31.8, obesity = 35%, diabetes = 16%, hypertension = 39%,
      IHD = 5%, Mean Epworth Sleepiness Scale score (ESS) = 8.3. The prevalence of
      unrecognized OSA was very high: 71% had an AHI > 5/h, 33% had an AHI > 15/h, and
      16% had an AHI > 30/h. The ApneaLink+O2 device yielded technically adequate
      studies in 93% of cases. CONCLUSION: The study shows that a "real world" simple
      low cost case finding and management program, based on unattended home monitoring
      for OSA, can work well in a population with risk factors and comorbidities
      associated with OSA, independent of the presence of symptoms. The prevalence of
      unrecognized OSA was very high.

PMID- 23853563
TI  - Obstructive sleep apnea in patients with end-stage lung disease.
AB  - OBJECTIVES: Little is known about the rate of obstructive sleep apnea (OSA) in
      patients with end stage lung disease (ESLD). Given the potential deleterious
      effect of OSA in these patients, we assessed the case-rate and severity of OSA
      and described associated patient characteristics. METHODS: Retrospective survey
      of 60 patients with ESLD referred for lung transplantation evaluation.
      Demographic, polysomnographic, spirometric, and medication utilization data were
      extracted and analyzed. RESULTS: As demographic and polysomnographic data did not
      differ between obstructive and restrictive patients, we present analysis of
      pooled data. Demographics/physiology: median age was 58.5 years, 52% males, mean
      BMI 32.3 kg/m(2), 52% obstructive. Sleep variables (all medians): total sleep
      time (TST) 312 min, sleep efficiency 77%, minimal oxygen saturation 84%, apnea
      hypopnea (AHI) 9.7, respiratory disturbance index (RDI) 12.7 events/h of sleep.
      Sixty-seven percent had RDI > 5; 21% had RDI between 15 and 30; and 21% had RDI >
      30. Periodic limb movement index >= 15/h sleep was present in 21.7%. An
      independent positive correlation between DLCO% and RDI was noted (r = 0.41, p <
      0.01). The minimal oxygen saturation was negatively correlated with the RDI (r = 
      0.34, p < 0.01). The use of ACE inhibitors was associated with moderate-to-severe
      OSA (odd ratio of 4.67, CI 1.45-15.03; p = 0.017). CONCLUSIONS: In patients with
      ESLD, organic sleep disorders are common. Greater severity of OSA was associated
      with the higher DLCO% and lower oxygen saturation.

PMID- 23853564
TI  - Inter-observer reliability of candidate predictive morphometric measurements for
      women with suspected obstructive sleep apnea.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) is increasingly recognized as a public
      health concern. Definitive diagnosis is by overnight polysomnographic (PSG)
      examination. Identification of clinical predictors would be beneficial in helping
      prioritize high-risk patients for assessment. Practical application of
      morphometric predictive variables would require a high level of reproducibility
      in a clinical setting. In this study, our objective was to evaluate reliability
      between observers in measurements of candidate morphometric parameters in women.
      DESIGN AND METHODS: This was a prospective study of 71 women who had been
      referred for PSG with suspected OSA. Selected morphometric parameters were
      measured independently in the sleep laboratory by two trained sleep physicians.
      RESULTS: Neck circumference and truncal measurements for lower costal,
      midabdominal, and hip circumferences had higher reliability coefficients
      (intraclass correlation coefficients [ICC] of 0.78, 0.95, 0.95, and 0.81) than
      the smaller dimension measurements, including cricomental distance or
      retrognathia (ICC of 0.04 and 0.17). Of the women participating in this study, 50
      of 71 had apnea-hypopnea indexes (AHI) >= 5. Body mass index (BMI), neck
      circumference, lower costal girth, midabdominal girth, and hip girth were all
      significantly higher (p < 0.001-0.004) in women with AHI >= 5. CONCLUSIONS: There
      was wide variation in inter-observer reliability for different physical
      dimensions. We propose that any clinical morphologic measurement employed in
      predictive modeling should be reliably reproducible in clinical setting
      conditions. Our findings support the use of several truncal measures, BMI, and
      neck circumference as predictive measures in women undergoing evaluation for OSA.

PMID- 23853565
TI  - Validating actigraphy as a measure of sleep for preschool children.
AB  - STUDY OBJECTIVES: The algorithms used to derive sleep variables from actigraphy
      were developed with adults. Because children change position during sleep more
      often than adults, algorithms may detect wakefulness when the child is actually
      sleeping (false negative). This study compares the validity of three algorithms
      for detecting sleep with actigraphy by comparing them to PSG in preschoolers. The
      putative influence of device location (wrist or ankle) is also examined. METHODS:
      Twelve children aged 2 to 5 years simultaneously wore an actigraph on an ankle
      and a wrist (Actiwatch-L, Mini-Mitter/Respironics) during a night of PSG
      recording at home. Three algorithms were tested: one recommended for adults and
      two designed to decrease false negative detection of sleep in children. RESULTS:
      Actigraphy generally showed good sensitivity (> 95%; PSG sleep detection) but low
      specificity (+/- 50%; PSG wake detection). Intraclass correlations between PSG
      and actigraphy variables were strong (> 0.80) for sleep latency, sleep duration,
      and sleep efficiency, but weak for number of awakenings (< 0.40). The two
      algorithms designed for children enhanced the validity of actigraphy in
      preschoolers and increased the proportion of actigraphy-scored wake epochs scored
      that were also PSG-identified as wake. Sleep variables derived from the ankle and
      wrist were not statistically different. CONCLUSION: Despite the weak detection of
      wakefulness, Acti-watch-L appears to be a useful instrument for assessing sleep
      in preschoolers when used with an adapted algorithm.

PMID- 23853566
TI  - Heart rate variability in sleep-related migraine without aura.
AB  - OBJECTIVES: This is an observational study aimed to investigate the activity of
      autonomic nervous system during sleep in patients with sleep-related migraine.
      METHODS: Eight consecutive migraineurs without aura were enrolled (6 women and 2
      men), aged 30 to 62 years (mean 48.1 +/- 9.3 years). Inclusion criteria were:
      high frequency of attacks (> 5 per month) and occurrence of more than 75% of the
      attacks during sleep causing an awakening. Patients were compared with a control
      group of 55 healthy subjects (23 men and 32 women, mean age 54.2 +/- 13.0 years),
      and with a further control group of 8 age- and gender-matched healthy controls.
      Patient and controls underwent polysomnography and heart rate variability
      analysis. RESULTS: A significant reduction of the LF/HF ratio during N2 and N3
      sleep stages was observed in migraineurs compared with controls. No differences
      in sleep macrostructure were observed; cyclic alternating pattern (CAP) time and
      CAP rate were lower in migraineurs than in controls. CONCLUSIONS: These findings
      indicate a peculiar modification of the autonomic balance during sleep in sleep
      related migraine. The reduction of LF/HF ratio in NREM sleep was observed in
      controls, but it was quantitatively much more evident in migraineurs. Changes in
      LF/HF could be consequent to an autonomic unbalance which could manifest
      selectively (or alternatively become more evident) during sleep. These findings,
      together with the reduction in CAP rate, could be an expression of reduced
      arousability during sleep in patients with sleep-related migraine. The
      simultaneous involvement of the autonomic, arousal, and pain systems might
      suggest involvement of the hypothalamic pathways.

PMID- 23853567
TI  - Status cataplecticus precipitated by abrupt withdrawal of venlafaxine.
AB  - Status cataplecticus is a rare manifestation of narcolepsy with cataplexy
      episodes recurring for hours or days, without a refractory period, in the absence
      of emotional triggers. This case highlights a narcoleptic patient who developed
      status cataplecticus after abrupt withdrawal of venlafaxine.

PMID- 23853568
TI  - Nocturnal diaphoresis secondary to mild obstructive sleep apnea in a patient with
      a history of two malignancies.
AB  - Numerous medical disorders, including obstructive sleep apnea, may cause
      nocturnal diaphoresis. Previous work has associated severe obstructive sleep
      apnea with nocturnal diaphoresis. This case report is of import as our patient
      with severe nocturnal diaphoresis manifested only mild sleep apnea, and, for
      years, his nocturnal diaphoresis was ascribed to other causes, i.e., first
      prostate cancer and then follicular B-cell lymphoma. Additionally, it was the
      nocturnal diaphoresis and not more common symptoms of obstructive sleep apnea,
      such as snoring, that led to the definitive diagnosis of his sleep apnea and then
      to treatment with a gratifying resolution of his onerous symptom.

PMID- 23853569
TI  - Defending sleepwalkers with science and an illustrative case.
AB  - OBJECTIVE: To test whether laboratory-based research differentiating sleepwalkers
      (SW) from controls (C) can be applied in an uncontrolled forensic case as
      evidence the alleged crime was committed during an arousal from sleep in which
      the mind is not fully conscious due to a SW disorder. METHODS: A PSG study
      recorded 8 months after the defendant was charged was analyzed independently by
      spectral analysis. Slow wave activity (SWA) and cyclic alternating pattern (CAP)
      rates were computed. Clinical interviews and police records were reviewed for
      data re: the defendant's sleep prior to the event and use of drugs, alcohol, and
      stimulants. RESULTS: The SWA distribution was abnormally low and flat,
      significantly lower than published controls; in the first NREM cycle, CAP rate 55
      was above normal. Two weeks of prior sleep deprivation was confirmed from
      interviews and defendant's observed daytime sleepiness. Caffeine intake the day
      before the event was calculated at 826 mg over 14 hours. Snoring and a mild
      breathing disorder were present in the PSG. CONCLUSION: Testimony based on
      spectral analysis of PSG recorded following an alleged criminal event supported a
      SW explanation for the non-rational behaviors charged. The defendant was
      acquitted of all charges and has been successfully treated.

PMID- 23853570
TI  - Ventricular or pseudo-ventricular tachycardia on polysomnogram.

PMID- 23853571
TI  - Is prediction of CPAP adherence in obstructive sleep apnea in the perioperative
      setting feasible?

PMID- 23853572
TI  - CPAP adherence during the perioperative period.

PMID- 23853575
TI  - Glycan masking of Plasmodium vivax Duffy Binding Protein for probing protein
      binding function and vaccine development.
AB  - Glycan masking is an emerging vaccine design strategy to focus antibody responses
      to specific epitopes, but it has mostly been evaluated on the already heavily
      glycosylated HIV gp120 envelope glycoprotein. Here this approach was used to
      investigate the binding interaction of Plasmodium vivax Duffy Binding Protein
      (PvDBP) and the Duffy Antigen Receptor for Chemokines (DARC) and to evaluate if
      glycan-masked PvDBPII immunogens would focus the antibody response on key
      interaction surfaces. Four variants of PVDBPII were generated and probed for
      function and immunogenicity. Whereas two PvDBPII glycosylation variants with
      increased glycan surface coverage distant from predicted interaction sites had
      equivalent binding activity to wild-type protein, one of them elicited slightly
      better DARC-binding-inhibitory activity than wild-type immunogen. Conversely, the
      addition of an N-glycosylation site adjacent to a predicted PvDBP interaction
      site both abolished its interaction with DARC and resulted in weaker inhibitory
      antibody responses. PvDBP is composed of three subdomains and is thought to
      function as a dimer; a meta-analysis of published PvDBP mutants and the new DBPII
      glycosylation variants indicates that critical DARC binding residues are
      concentrated at the dimer interface and along a relatively flat surface spanning
      portions of two subdomains. Our findings suggest that DARC-binding-inhibitory
      antibody epitope(s) lie close to the predicted DARC interaction site, and that
      addition of N-glycan sites distant from this site may augment inhibitory
      antibodies. Thus, glycan resurfacing is an attractive and feasible tool to
      investigate protein structure-function, and glycan-masked PvDBPII immunogens
      might contribute to P. vivax vaccine development. 

PMID- 23853576
TI  - Papillomaviruses use recombination-dependent replication to vegetatively amplify
      their genomes in differentiated cells.

PMID- 23853577
TI  - Babesia: an emerging infectious threat in transfusion medicine.

PMID- 23853578
TI  - Stress relief during host infection: The phage shock protein response supports
      bacterial virulence in various ways.

PMID- 23853579
TI  - DNA methylation impacts gene expression and ensures hypoxic survival of
      Mycobacterium tuberculosis.
AB  - DNA methylation regulates gene expression in many organisms. In eukaryotes, DNA
      methylation is associated with gene repression, while it exerts both activating
      and repressive effects in the Proteobacteria through largely locus-specific
      mechanisms. Here, we identify a critical DNA methyltransferase in M.
      tuberculosis, which we term MamA. MamA creates N6-methyladenine in a six base
      pair recognition sequence present in approximately 2,000 copies on each strand of
      the genome. Loss of MamA reduces the expression of a number of genes. Each has a
      MamA site located at a conserved position relative to the sigma factor -10
      binding site and transcriptional start site, suggesting that MamA modulates their
      expression through a shared, not locus-specific, mechanism. While strains lacking
      MamA grow normally in vitro, they are attenuated in hypoxic conditions,
      suggesting that methylation promotes survival in discrete host microenvironments.
      Interestingly, we demonstrate strikingly different patterns of DNA
      methyltransferase activity in different lineages of M. tuberculosis, which have
      been associated with preferences for distinct host environments and different
      disease courses in humans. Thus, MamA is the major functional adenine
      methyltransferase in M. tuberculosis strains of the Euro-American lineage while
      strains of the Beijing lineage harbor a point mutation that largely inactivates
      MamA but possess a second functional DNA methyltransferase. Our results indicate
      that MamA influences gene expression in M. tuberculosis and plays an important
      but strain-specific role in fitness during hypoxia.

PMID- 23853580
TI  - Rapid perturbation in viremia levels drives increases in functional avidity of
      HIV-specific CD8 T cells.
AB  - The factors determining the functional avidity and its relationship with the
      broad heterogeneity of antiviral T cell responses remain partially understood. We
      investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV
      infection (PHI) or chronic (progressive and non-progressive) infection. The
      functional avidity of HIV-specific CD8 T cells was not different between patients
      with progressive and non-progressive chronic infection. However, it was
      significantly lower in PHI patients at the time of diagnosis of acute infection
      and after control of virus replication following one year of successful
      antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower
      levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype,
      i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the
      functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI
      patients experiencing a virus rebound after spontaneous treatment interruption.
      This increase in functional avidity was associated with the accumulation of PD
      1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal.
      The increased TCR renewal may provide the mechanistic basis for the generation of
      high-avidity HIV-specific CD8 T cells. These results provide insights on the
      relationships between functional avidity, viremia, T-cell exhaustion and TCR
      renewal of antiviral CD8 T cell responses. 

PMID- 23853582
TI  - Interplay between siderophores and colibactin genotoxin biosynthetic pathways in
      Escherichia coli.
AB  - In Escherichia coli, the biosynthetic pathways of several small iron-scavenging
      molecules known as siderophores (enterobactin, salmochelins and yersiniabactin)
      and of a genotoxin (colibactin) are known to require a 4'-phosphopantetheinyl
      transferase (PPTase). Only two PPTases have been clearly identified: EntD and
      ClbA. The gene coding for EntD is part of the core genome of E. coli, whereas
      ClbA is encoded on the pks pathogenicity island which codes for colibactin.
      Interestingly, the pks island is physically associated with the high
      pathogenicity island (HPI) in a subset of highly virulent E. coli strains. The
      HPI carries the gene cluster required for yersiniabactin synthesis except for a
      gene coding its cognate PPTase. Here we investigated a potential interplay
      between the synthesis pathways leading to the production of siderophores and
      colibactin, through a functional interchangeability between EntD and ClbA. We
      demonstrated that ClbA could contribute to siderophores synthesis. Inactivation
      of both entD and clbA abolished the virulence of extra-intestinal pathogenic E.
      coli (ExPEC) in a mouse sepsis model, and the presence of either functional EntD
      or ClbA was required for the survival of ExPEC in vivo. This is the first report
      demonstrating a connection between multiple phosphopantetheinyl-requiring
      pathways leading to the biosynthesis of functionally distinct secondary
      metabolites in a given microorganism. Therefore, we hypothesize that the strict
      association of the pks island with HPI has been selected in highly virulent E.
      coli because ClbA is a promiscuous PPTase that can contribute to the synthesis of
      both the genotoxin and siderophores. The data highlight the complex regulatory
      interaction of various virulence features with different functions. The
      identification of key points of these networks is not only essential to the
      understanding of ExPEC virulence but also an attractive and promising target for
      the development of anti-virulence therapy strategies. 

PMID- 23853581
TI  - Targeting iron acquisition blocks infection with the fungal pathogens Aspergillus
      fumigatus and Fusarium oxysporum.
AB  - Filamentous fungi are an important cause of pulmonary and systemic morbidity and
      mortality, and also cause corneal blindness and visual impairment worldwide.
      Utilizing in vitro neutrophil killing assays and a model of fungal infection of
      the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates
      expression of iron chelators, heme and siderophore binding proteins and hepcidin
      in infected mice. In addition, we show that human neutrophils synthesize
      lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1
      or lactoferrin restricts fungal growth in vivo. Conversely, we show that
      exogenous iron or the xenosiderophore deferroxamine enhances fungal growth in
      infected mice. By examining mutant Aspergillus and Fusarium strains, we found
      that fungal transcriptional responses to low iron levels and extracellular
      siderophores are essential for fungal growth during infection. Further, we showed
      that targeting fungal iron acquisition or siderophore biosynthesis by topical
      application of iron chelators or statins reduces fungal growth in the cornea by
      60% and that dual therapy with the iron chelator deferiprone and statins further
      restricts fungal growth by 75%. Together, these studies identify specific host
      iron-chelating and fungal iron-acquisition mediators that regulate fungal growth,
      and demonstrate that therapeutic inhibition of fungal iron acquisition can be
      utilized to treat topical fungal infections. 

PMID- 23853583
TI  - An acidic microenvironment increases NK cell killing of Cryptococcus neoformans
      and Cryptococcus gattii by enhancing perforin degranulation.
AB  - Cryptococcus gattii and Cryptococcus neoformans are encapsulated yeasts that can
      produce a solid tumor-like mass or cryptococcoma. Analogous to malignant tumors,
      the microenvironment deep within a cryptococcoma is acidic, which presents unique
      challenges to host defense. Analogous to malignant cells, NK cells kill
      Cryptococcus. Thus, as in tumor defense, NK cells must kill yeast cells across a
      gradient from physiologic pH to less than 6 in the center of the cryptococcoma.
      As acidic pH inhibits anti-tumor activities of NK cells, we sought to determine
      if there was a similar reduction in the anticryptococcal activity of NK cells.
      Surprisingly, we found that both primary human NK cells and the human NK cell
      line, YT, have preserved or even enhanced killing of Cryptococcus in acidic,
      compared to physiological, pH. Studies to explore the mechanism of enhanced
      killing revealed that acidic pH does not increase the effector to target ratio,
      binding of cytolytic cells to Cryptococcus, or the active perforin content in
      effector cells. By contrast, perforin degranulation was greater at acidic pH, and
      increased degranulation was preceded by enhanced ERK1/2 phosphorylation, which is
      essential for killing. Moreover, using a replication defective ras1 knockout
      strain of Cryptococcus increased degranulation occurred during more rapid
      replication of the organisms. Finally, NK cells were found intimately associated
      with C. gattii within the cryptococcoma of a fatal infection. These results
      suggest that NK cells have amplified signaling, degranulation, and greater
      killing at low pH and when the organisms are replicating quickly, which would
      help maintain microbicidal host defense despite an acidic microenvironment. 

PMID- 23853584
TI  - The interactomes of influenza virus NS1 and NS2 proteins identify new host
      factors and provide insights for ADAR1 playing a supportive role in virus
      replication.
AB  - Influenza A NS1 and NS2 proteins are encoded by the RNA segment 8 of the viral
      genome. NS1 is a multifunctional protein and a virulence factor while NS2 is
      involved in nuclear export of viral ribonucleoprotein complexes. A yeast two
      hybrid screening strategy was used to identify host factors supporting NS1 and
      NS2 functions. More than 560 interactions between 79 cellular proteins and NS1
      and NS2 proteins from 9 different influenza virus strains have been identified.
      These interacting proteins are potentially involved in each step of the
      infectious process and their contribution to viral replication was tested by RNA
      interference. Validation of the relevance of these host cell proteins for the
      viral replication cycle revealed that 7 of the 79 NS1 and/or NS2-interacting
      proteins positively or negatively controlled virus replication. One of the main
      factors targeted by NS1 of all virus strains was double-stranded RNA binding
      domain protein family. In particular, adenosine deaminase acting on RNA 1 (ADAR1)
      appeared as a pro-viral host factor whose expression is necessary for optimal
      viral protein synthesis and replication. Surprisingly, ADAR1 also appeared as a
      pro-viral host factor for dengue virus replication and directly interacted with
      the viral NS3 protein. ADAR1 editing activity was enhanced by both viruses
      through dengue virus NS3 and influenza virus NS1 proteins, suggesting a similar
      virus-host co-evolution. 

PMID- 23853585
TI  - Critical and independent role for SOCS3 in either myeloid or T cells in
      resistance to Mycobacterium tuberculosis.
AB  - Suppressor of cytokine signalling 3 (SOCS3) negatively regulates STAT3 activation
      in response to several cytokines such as those in the gp130-containing IL-6
      receptor family. Thus, SOCS3 may play a major role in immune responses to
      pathogens. In the present study, the role of SOCS3 in M. tuberculosis infection
      was examined. All Socs3(fl/fl) LysM cre, Socs3(fl/fl) lck cre (with SOCS3
      deficient myeloid and lymphoid cells, respectively) and gp130(F/F) mice, with a
      mutation in gp130 that impedes binding to SOCS3, showed increased susceptibility
      to infection with M. tuberculosis. SOCS3 binding to gp130 in myeloid cells
      conveyed resistance to M. tuberculosis infection via the regulation of IL-6/STAT3
      signalling. SOCS3 was redundant for mycobacterial control by macrophages in
      vitro. Instead, SOCS3 expression in infected macrophages and DCs prevented the IL
      6-mediated inhibition of TNF and IL-12 secretion and contributed to a timely CD4+
      cell-dependent IFN-gamma expression in vivo. In T cells, SOCS3 expression was
      essential for a gp130-independent control of infection with M. tuberculosis, but
      was neither required for the control of infection with attenuated M. bovis BCG
      nor for M. tuberculosis in BCG-vaccinated mice. Socs3(fl/fl) lck cre mice showed
      an increased frequency of gammadelta+ T cells in different organs and an enhanced
      secretion of IL-17 by gammadelta+ T cells in response to infection. Socs3(fl/fl)
      lck cre gammadelta+ T cells impaired the control of infection with M.
      tuberculosis. Thus, SOCS3 expression in either lymphoid or myeloid cells is
      essential for resistance against M. tuberculosis via discrete mechanisms. 

PMID- 23853586
TI  - The HCMV gH/gL/UL128-131 complex triggers the specific cellular activation
      required for efficient viral internalization into target monocytes.
AB  - We have established that HCMV acts as a specific ligand engaging and activating
      cellular integrins on monocytes. As a result, integrin signaling via Src
      activation leads to the functional activation of paxillin required for efficient
      viral entry and for the biological changes in monocytes needed for viral
      dissemination. These biological/molecular changes allow HCMV to use monocytes as
      "vehicles" for systemic spread and the establishment of lifelong persistence.
      However, it remains unresolved how HCMV specifically induces this observed
      monocyte activation. It was previously demonstrated that the HCMV gH/gL/UL128-131
      glycoprotein complex facilitates viral entry into biologically relevant cell
      types. Nevertheless, the mechanism by which the gH/gL/UL128-131 complex promotes
      this process is unknown. We now show that only HCMV virions possessing the
      gH/gL/UL128-131 complex are capable of activating integrin/Src/paxillin-signaling
      in monocytes. In fibroblasts, this signaling is reversed, such that virus lacking
      the gH/gL/UL128-131 complex is the only virus able to induce the paxillin
      activation cascade. The presence of the gH/gL/UL128-131 complex also may have an
      inhibitory effect on integrin-mediated signaling pathway in fibroblasts.
      Furthermore, we demonstrate that the presence of the gH/gL/UL128-131 complex on
      the viral envelope, through its activation of the integrin/Src/paxillin pathway,
      is necessary for efficient HCMV internalization into monocytes and that
      appropriate actin and dynamin regulation is critical for this entry process.
      Importantly, productive infection in monocyte-derived macrophages was seen only
      in cells exposed to HCMV expressing the gH/gL/UL128-131 complex. From our data,
      the HCMV gH/gL/U128-131 complex emerges as the specific ligand driving the
      activation of the receptor-mediated signaling required for the regulation of the
      actin cytoskeleton and, consequently, for efficient and productive
      internalization of HCMV into monocytes. To our knowledge, our studies demonstrate
      a possible molecular mechanism for why the gH/gL/UL128-131 complex dictates HCMV
      tropism and why the complex is lost as clinical isolates are passaged in the
      laboratory. 

PMID- 23853587
TI  - Structure and function of a fungal adhesin that binds heparin and mimics
      thrombospondin-1 by blocking T cell activation and effector function.
AB  - Blastomyces adhesin-1 (BAD-1) is a 120-kD surface protein on B. dermatitidis
      yeast. We show here that BAD-1 contains 41 tandem repeats and that deleting even
      half of them impairs fungal pathogenicity. According to NMR, the repeats form
      tightly folded 17-amino acid loops constrained by a disulfide bond linking
      conserved cysteines. Each loop contains a highly conserved WxxWxxW motif found in
      thrombospondin-1 (TSP-1) type 1 heparin-binding repeats. BAD-1 binds heparin
      specifically and saturably, and is competitively inhibited by soluble heparin,
      but not related glycosaminoglycans. According to SPR analysis, the affinity of
      BAD-1 for heparin is 33 nM+/-14 nM. Putative heparin-binding motifs are found
      both at the N-terminus and within each tandem repeat loop. Like TSP-1, BAD-1
      blocks activation of T cells in a manner requiring the heparan sulfate-modified
      surface molecule CD47, and impairs effector functions. The tandem repeats of BAD
      1 thus confer pathogenicity, harbor motifs that bind heparin, and suppress T-cell
      activation via a CD47-dependent mechanism, mimicking mammalian TSP-1. 

PMID- 23853589
TI  - Emerging infectious diseases: threats to human health and global stability.

PMID- 23853588
TI  - Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR
      and also conscripts RHA/DHX9 to promote expanded host tropism and viral
      replication.
AB  - Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of
      dsRNA-binding proteins that antagonize the cellular interferon signaling
      pathways. In order to investigate additional functions of M029, we have
      constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5
      tagged M029 MYXV. We found that M029 plays a pivotal role in determining the
      cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses
      were able to replicate only in engineered cell lines that stably express a
      complementing protein, such as vaccinia E3, but underwent abortive or abated
      infection in all other tested mammalian cell lines. The M029-minus viruses were
      dramatically attenuated in susceptible host European rabbits and caused no
      observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that
      M029 expressed as an early viral protein is localized in both the nuclear and
      cytosolic compartments in virus-infected cells, and is also incorporated into
      virions. Using proteomic approaches, we have identified Protein Kinase R (PKR)
      and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein.
      In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner,
      while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown
      in human cells rescued the replication defect of the M029-knockout viruses.
      Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could
      then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This
      indicates that M029 not only inhibits generic PKR anti-viral pathways, but also
      binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus
      replication in THP1 cells. Thus, M029 is a critical host range and virulence
      factor for MYXV that is required for replication in all mammalian cells by
      antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral
      RHA/DHX9 to promote viral replication specifically in myeloid cells. 

PMID- 23853590
TI  - Ethnic variation in inflammatory profile in tuberculosis.
AB  - Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease
      in patients of particular genetic ancestry, and elicit different patterns of
      cytokine and chemokine secretion when cultured with human macrophages in vitro.
      Circulating and antigen-stimulated concentrations of these inflammatory mediators
      might therefore be expected to vary significantly between tuberculosis patients
      of different ethnic origin. Studies to characterise such variation, and to
      determine whether it relates to host or bacillary factors, have not been
      conducted. We therefore compared circulating and antigen-stimulated
      concentrations of 43 inflammatory mediators and 14 haematological parameters
      (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry
      vs. 83 patients of Eurasian ancestry in London, UK, and investigated the
      influence of bacillary and host genotype on these profiles. Despite having
      similar demographic and clinical characteristics, patients of differing ancestry
      exhibited distinct inflammatory profiles at presentation: those of African
      ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11
      and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and
      higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These
      differences associated with ethnic variation in host DBP genotype, but not with
      ethnic variation in MTB strain. Ethnic differences in inflammatory profile became
      more marked following initiation of antimicrobial therapy, and immunological
      correlates of speed of elimination of MTB from the sputum differed between
      patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto
      unappreciated degree of ethnic heterogeneity in inflammatory profile in
      tuberculosis patients that associates primarily with ethnic variation in host,
      rather than bacillary, genotype. Candidate immunodiagnostics and immunological
      biomarkers of response to antimicrobial therapy should be derived and validated
      in tuberculosis patients of different ethnic origin. 

PMID- 23853591
TI  - A key role for the urokinase plasminogen activator (uPA) in invasive Group A
      streptococcal infection.
AB  - Recruitment of the serine protease plasmin is central to the pathogenesis of many
      bacterial species, including Group A streptococcus (GAS), a leading cause of
      morbidity and mortality globally. A key process in invasive GAS disease is the
      ability to accumulate plasmin at the cell surface, however the role of host
      activators of plasminogen in this process is poorly understood. Here, we
      demonstrate for the first time that the urokinase-type plasminogen activator
      (uPA) contributes to plasmin recruitment and subsequent invasive disease
      initiation in vivo. In the absence of a source of host plasminogen activators,
      streptokinase (Ska) was required to facilitate cell surface plasmin acquisition
      by GAS. However, in the absence of Ska, host activators were sufficient to
      promote cell surface plasmin acquisition by GAS strain 5448 during incubation
      with plasminogen or human plasma. Furthermore, GAS were able mediate a
      significant increase in the activation of zymogen pro-uPA in human plasma. In
      order to assess the contribution of uPA to invasive GAS disease, a previously
      undescribed transgenic mouse model of infection was employed. Both C57/black 6J,
      and AlbPLG1 mice expressing the human plasminogen transgene, were significantly
      more susceptible to invasive GAS disease than uPA-/- mice. The observed decrease
      in virulence in uPA-/-mice was found to correlate directly with a decrease in
      bacterial dissemination and reduced cell surface plasmin accumulation by GAS.
      These findings have significant implications for our understanding of GAS
      pathogenesis, and research aimed at therapeutic targeting of plasminogen
      activation in invasive bacterial infections. 

PMID- 23853592
TI  - Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV
      infected rhesus macaques treated with interleukin (IL)-21.
AB  - In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs),
      preferential depletion of CD4+ Th17 cells correlates with mucosal immune
      dysfunction and disease progression. Interleukin (IL)-21 promotes differentiation
      of Th17 cells, long-term maintenance of functional CD8+ T cells, and
      differentiation of memory B cells and antibody-secreting plasma cells. We
      hypothesized that administration of IL-21 will improve mucosal function in the
      context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12
      RMs with SIV(mac239) and at day 14 post-infection treated six of them with rhesus
      rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or
      systemic immune activation. Compared to untreated animals, IL-21-treated RMs
      showed (i) higher expression of perforin and granzyme B in total and SIV-specific
      CD8+ T cells and (ii) higher levels of intestinal Th17 cells. Remarkably,
      increased levels of Th17 cells were associated with reduced levels of intestinal
      T cell proliferation, microbial translocation and systemic
      activation/inflammation in the chronic infection. In conclusion, IL-21-treatment
      in SIV-infected RMs improved mucosal immune function through enhanced
      preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted
      to test its potential use during chronic infection in conjunction with
      antiretroviral therapy.

PMID- 23853593
TI  - B cells regulate neutrophilia during Mycobacterium tuberculosis infection and BCG
      vaccination by modulating the interleukin-17 response.
AB  - We have previously demonstrated that B cells can shape the immune response to
      Mycobacterium tuberculosis, including the level of neutrophil infiltration and
      granulomatous inflammation at the site of infection. The present study examined
      the mechanisms by which B cells regulate the host neutrophilic response upon
      exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To
      address these questions, a murine aerosol infection tuberculosis (TB) model and
      an intradermal (ID) ear BCG immunization mouse model, involving both the MUMT
      strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17
      neutralization and neutrophil depletion experiments using these systems provide
      evidence that B cells can regulate neutrophilia by modulating the IL-17 response
      during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at
      the site of immunization in B cell-deficient mice adversely affects dendritic
      cell (DC) migration to the draining lymph nodes and attenuates the development of
      the vaccine-induced Th1 response. The results suggest that B cells are required
      for the development of optimal protective anti-TB immunity upon BCG vaccination
      by regulating the IL-17/neutrophilic response. Administration of sera derived
      from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung
      neutrophilia phenotype in tuberculous MUMT mice. Together, these observations
      provide insight into the mechanisms by which B cells and humoral immunity
      modulate vaccine-induced Th1 response and regulate neutrophila during M.
      tuberculosis infection and BCG immunization. 

PMID- 23853594
TI  - Evidence for a continuous drift of the HIV-1 species towards higher resistance to
      neutralizing antibodies over the course of the epidemic.
AB  - We compared the neutralization sensitivity of early/transmitted HIV-1 variants
      from patients infected by subtype B viruses at 3 periods of the epidemic (1987
      1991, 1996-2000, 2006-2010). Infectious pseudotyped viruses expressing envelope
      glycoproteins representative of the viral quasi-species infecting each patient
      were tested for sensitivity to neutralization by pools of sera from HIV-1
      chronically infected patients and by an updated panel of 13 human monoclonal
      neutralizing antibodies (HuMoNAbs). A progressive significantly enhanced
      resistance to neutralization was observed over calendar time, by both human sera
      and most of the HuMoNAbs tested (b12, VRC01, VRC03, NIH45-46(G54W), PG9, PG16,
      PGT121, PGT128, PGT145). Despite this evolution, a combination of two HuMoNAbs
      (NIH45-46(G54W) and PGT128) still would efficiently neutralize the most
      contemporary transmitted variants. In addition, we observed a significant
      reduction of the heterologous neutralizing activity of sera from individuals
      infected most recently (2003-2007) compared to patients infected earlier (1987
      1991), suggesting that the increasing resistance of the HIV species to
      neutralization over time coincided with a decreased immunogenicity. These data
      provide evidence for an ongoing adaptation of the HIV-1 species to the humoral
      immunity of the human population, which may add an additional obstacle to the
      design of an efficient HIV-1 vaccine. 

PMID- 23853595
TI  - Reprogramming of murine macrophages through TLR2 confers viral resistance via
      TRAF3-mediated, enhanced interferon production.
AB  - The cell surface/endosomal Toll-like Receptors (TLRs) are instrumental in
      initiating immune responses to both bacteria and viruses. With the exception of
      TLR2, all TLRs and cytosolic RIG-I-like receptors (RLRs) with known virus-derived
      ligands induce type I interferons (IFNs) in macrophages or dendritic cells.
      Herein, we report that prior ligation of TLR2, an event previously shown to
      induce "homo" or "hetero" tolerance, strongly "primes" macrophages for increased
      Type I IFN production in response to subsequent TLR/RLR signaling. This occurs by
      increasing activation of the transcription factor, IFN Regulatory Factor-3 (IRF
      3) that, in turn, leads to enhanced induction of IFN-beta, while expression of
      other pro-inflammatory genes are suppressed (tolerized). In vitro or in vivo
      "priming" of murine macrophages with TLR2 ligands increase virus-mediated IFN
      induction and resistance to infection. This priming effect of TLR2 is mediated by
      the selective upregulation of the K63 ubiquitin ligase, TRAF3. Thus, we provide a
      mechanistic explanation for the observed antiviral actions of MyD88-dependent
      TLR2 and further define the role of TRAF3 in viral innate immunity. 

PMID- 23853596
TI  - Trichomonas vaginalis exosomes deliver cargo to host cells and mediate
      host?parasite interactions.
AB  - Trichomonas vaginalis is a common sexually transmitted parasite that colonizes
      the human urogential tract where it remains extracellular and adheres to
      epithelial cells. Infections range from asymptomatic to highly inflammatory,
      depending on the host and the parasite strain. Here, we use a combination of
      methodologies including cell fractionation, immunofluorescence and electron
      microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to
      examine pathogenic properties of T. vaginalis. We have found that T.vaginalis
      produces and secretes microvesicles with physical and biochemical properties
      similar to mammalian exosomes. The parasite-derived exosomes are characterized by
      the presence of RNA and core, conserved exosomal proteins as well as parasite
      specific proteins. We demonstrate that T. vaginalis exosomes fuse with and
      deliver their contents to host cells and modulate host cell immune responses.
      Moreover, exosomes from highly adherent parasite strains increase the adherence
      of poorly adherent parasites to vaginal and prostate epithelial cells. In
      contrast, exosomes from poorly adherent strains had no measurable effect on
      parasite adherence. Exosomes from parasite strains that preferentially bind
      prostate cells increased binding of parasites to these cells relative to vaginal
      cells. In addition to establishing that parasite exosomes act to modulate
      host?parasite interactions, these studies are the first to reveal a potential
      role for exosomes in promoting parasite?parasite communication and host cell
      colonization. 

PMID- 23853597
TI  - IL-22 and IDO1 affect immunity and tolerance to murine and human vaginal
      candidiasis.
AB  - The ability to tolerate Candida albicans, a human commensal of the
      gastrointestinal tract and vagina, implicates that host defense mechanisms of
      resistance and tolerance cooperate to limit fungal burden and inflammation at the
      different body sites. We evaluated resistance and tolerance to the fungus in
      experimental and human vulvovaginal candidiasis (VVC) as well as in recurrent VVC
      (RVVC). Resistance and tolerance mechanisms were both activated in murine VVC,
      involving IL-22 and IL-10-producing regulatory T cells, respectively, with a
      major contribution by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 was
      responsible for the production of tolerogenic kynurenines, such that replacement
      therapy with kynurenines restored immunoprotection to VVC. In humans, two
      functional genetic variants in IL22 and IDO1 genes were found to be associated
      with heightened resistance to RVVC, and they correlated with increased local
      expression of IL-22, IDO1 and kynurenines. Thus, IL-22 and IDO1 are crucial in
      balancing resistance with tolerance to Candida, their deficiencies are risk
      factors for RVVC, and targeting tolerance via therapeutic kynurenines may benefit
      patients with RVVC. 

PMID- 23853598
TI  - Tetherin/BST-2 antagonism by Nef depends on a direct physical interaction between
      Nef and tetherin, and on clathrin-mediated endocytosis.
AB  - Nef is the viral gene product employed by the majority of primate lentiviruses to
      overcome restriction by tetherin (BST-2 or CD317), an interferon-inducible
      transmembrane protein that inhibits the detachment of enveloped viruses from
      infected cells. Although the mechanisms of tetherin antagonism by HIV-1 Vpu and
      HIV-2 Env have been investigated in detail, comparatively little is known about
      tetherin antagonism by SIV Nef. Here we demonstrate a direct physical interaction
      between SIV Nef and rhesus macaque tetherin, define the residues in Nef required
      for tetherin antagonism, and show that the anti-tetherin activity of Nef is
      dependent on clathrin-mediated endocytosis. SIV Nef co-immunoprecipitated with
      rhesus macaque tetherin and the Nef core domain bound directly to a peptide
      corresponding to the cytoplasmic domain of rhesus tetherin by surface plasmon
      resonance. An analysis of alanine-scanning substitutions identified residues
      throughout the N-terminal, globular core and flexible loop regions of Nef that
      were required for tetherin antagonism. Although there was significant overlap
      with sequences required for CD4 downregulation, tetherin antagonism was
      genetically separable from this activity, as well as from other Nef functions,
      including MHC class I-downregulation and infectivity enhancement. Consistent with
      a role for clathrin and dynamin 2 in the endocytosis of tetherin, dominant
      negative mutants of AP180 and dynamin 2 impaired the ability of Nef to
      downmodulate tetherin and to counteract restriction. Taken together, these
      results reveal that the mechanism of tetherin antagonism by Nef depends on a
      physical interaction between Nef and tetherin, requires sequences throughout Nef,
      but is genetically separable from other Nef functions, and leads to the removal
      of tetherin from sites of virus release at the plasma membrane by clathrin
      mediated endocytosis. 

PMID- 23853599
TI  - CD40 activation rescues antiviral CD8+ T cells from PD-1-mediated exhaustion.
AB  - The intrahepatic immune environment is normally biased towards tolerance.
      Nonetheless, effective antiviral immune responses can be induced against
      hepatotropic pathogens. To examine the immunological basis of this paradox we
      studied the ability of hepatocellularly expressed hepatitis B virus (HBV) to
      activate immunologically naive HBV-specific CD8+ T cell receptor (TCR) transgenic
      T cells after adoptive transfer to HBV transgenic mice. Intrahepatic priming
      triggered vigorous in situ T cell proliferation but failed to induce interferon
      gamma production or cytolytic effector function. In contrast, the same T cells
      differentiated into cytolytic effector T cells in HBV transgenic mice if
      Programmed Death 1 (PD-1) expression was genetically ablated, suggesting that
      intrahepatic antigen presentation per se triggers negative regulatory signals
      that prevent the functional differentiation of naive CD8+ T cells. Surprisingly,
      coadministration of an agonistic anti-CD40 antibody (alphaCD40) inhibited PD-1
      induction and restored T cell effector function, thereby inhibiting viral gene
      expression and causing a necroinflammatory liver disease. Importantly, the
      depletion of myeloid dendritic cells (mDCs) strongly diminished the alphaCD40
      mediated functional differentiation of HBV-specific CD8+ T cells, suggesting that
      activation of mDCs was responsible for the functional differentiation of HBV
      specific CD8+ T cells in alphaCD40 treated animals. These results demonstrate
      that antigen-specific, PD-1-mediated CD8+ T cell exhaustion can be rescued by
      CD40-mediated mDC-activation.

PMID- 23853600
TI  - Irf8-regulated genomic responses drive pathological inflammation during cerebral
      malaria.
AB  - Interferon Regulatory Factor 8 (IRF8) is required for development, maturation and
      expression of anti-microbial defenses of myeloid cells. BXH2 mice harbor a
      severely hypomorphic allele at Irf8 (Irf8(R294C)) that causes susceptibility to
      infection with intracellular pathogens including Mycobacterium tuberculosis. We
      report that BXH2 are completely resistant to the development of cerebral malaria
      (ECM) following Plasmodium berghei ANKA infection. Comparative transcriptional
      profiling of brain RNA as well as chromatin immunoprecipitation and high
      throughput sequencing (ChIP-seq) was used to identify IRF8-regulated genes whose
      expression is associated with pathological acute neuroinflammation. Genes
      increased by infection were strongly enriched for IRF8 binding sites, suggesting
      that IRF8 acts as a transcriptional activator in inflammatory programs. These
      lists were enriched for myeloid-specific pathways, including interferon
      responses, antigen presentation and Th1 polarizing cytokines. We show that
      inactivation of several of these downstream target genes (including the Irf8
      transcription partner Irf1) confers protection against ECM. ECM-resistance in
      Irf8 and Irf1 mutants is associated with impaired myeloid and lymphoid cells
      function, including production of IL12p40 and IFNgamma. We note strong overlap
      between genes bound and regulated by IRF8 during ECM and genes regulated in the
      lungs of M. tuberculosis infected mice. This IRF8-dependent network contains
      several genes recently identified as risk factors in acute and chronic human
      inflammatory conditions. We report a common core of IRF8-bound genes forming a
      critical inflammatory host-response network.

PMID- 23853601
TI  - Inhibition of hepatitis B virus replication by the host zinc finger antiviral
      protein.
AB  - The zinc finger antiviral protein (ZAP) is a mammalian host restriction factor
      that inhibits the replication of a variety of RNA viruses, including
      retroviruses, alphaviruses and filoviruses, through interaction with the ZAP
      responsive elements (ZRE) in viral RNA, and recruiting the exosome to degrade RNA
      substrate. Hepatitis B virus (HBV) is a pararetrovirus that replicates its
      genomic DNA via reverse transcription of a viral pregenomic (pg) RNA precursor.
      Here, we demonstrate that the two isoforms of human ZAP (hZAP-L and -S) inhibit
      HBV replication in human hepatocyte-derived cells through posttranscriptional
      down-regulation of viral pgRNA. Mechanistically, the zinc finger motif-containing
      N-terminus of hZAP is responsible for the reduction of HBV RNA, and the integrity
      of the four zinc finger motifs is essential for ZAP to bind to HBV RNA and
      fulfill its antiviral function. The ZRE sequences conferring the susceptibility
      of viral RNA to ZAP-mediated RNA decay were mapped to the terminal redundant
      region (nt 1820-1918) of HBV pgRNA. In agreement with its role as a host
      restriction factor and as an innate immune mediator for HBV infection, ZAP was
      upregulated in cultured primary human hepatocytes and hepatocyte-derived cells
      upon IFN-alpha treatment or IPS-1 activation, and in the livers of hepatitis B
      patients during immune active phase. Knock down of ZAP expression increased the
      level of HBV RNA and partially attenuated the antiviral effect elicited by IPS-1
      in cell cultures. In summary, we demonstrated that ZAP is an intrinsic host
      antiviral factor with activity against HBV through down-regulation of viral RNA,
      and that ZAP plays a role in the innate control of HBV replication. Our findings
      thus shed light on virus-host interaction, viral pathogenesis, and antiviral
      approaches. 

PMID- 23853602
TI  - Mutated and bacteriophage T4 nanoparticle arrayed F1-V immunogens from Yersinia
      pestis as next generation plague vaccines.
AB  - Pneumonic plague is a highly virulent infectious disease with 100% mortality
      rate, and its causative organism Yersinia pestis poses a serious threat for
      deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine
      against plague. The polymeric bacterial capsular protein F1, a key component of
      the currently tested bivalent subunit vaccine consisting, in addition, of low
      calcium response V antigen, has high propensity to aggregate, thus affecting its
      purification and vaccine efficacy. We used two basic approaches, structure-based
      immunogen design and phage T4 nanoparticle delivery, to construct new plague
      vaccines that provided complete protection against pneumonic plague. The NH2
      terminal beta-strand of F1 was transplanted to the COOH-terminus and the sequence
      flanking the beta-strand was duplicated to eliminate polymerization but to retain
      the T cell epitopes. The mutated F1 was fused to the V antigen, a key virulence
      factor that forms the tip of the type three secretion system (T3SS). The F1mut-V
      protein showed a dramatic switch in solubility, producing a completely soluble
      monomer. The F1mut-V was then arrayed on phage T4 nanoparticle via the small
      outer capsid protein, Soc. The F1mut-V monomer was robustly immunogenic and the
      T4-decorated F1mut-V without any adjuvant induced balanced TH1 and TH2 responses
      in mice. Inclusion of an oligomerization-deficient YscF, another component of the
      T3SS, showed a slight enhancement in the potency of F1-V vaccine, while deletion
      of the putative immunomodulatory sequence of the V antigen did not improve the
      vaccine efficacy. Both the soluble (purified F1mut-V mixed with alhydrogel) and
      T4 decorated F1mut-V (no adjuvant) provided 100% protection to mice and rats
      against pneumonic plague evoked by high doses of Y. pestis CO92. These novel
      platforms might lead to efficacious and easily manufacturable next generation
      plague vaccines.

PMID- 23853603
TI  - Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation.
AB  - A main determinant of prolonged Trypanosoma brucei infection and transmission and
      success of the parasite is the interplay between host acquired immunity and
      antigenic variation of the parasite variant surface glycoprotein (VSG) coat.
      About 0.1% of trypanosome divisions produce a switch to a different VSG through
      differential expression of an archive of hundreds of silent VSG genes and
      pseudogenes, but the patterns and extent of the trypanosome diversity phenotype,
      particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA
      sequencing to estimate variant richness and test whether pseudogenes contribute
      to antigenic variation. We show that individual growth peaks can contain at least
      15 distinct variants, are estimated computationally to comprise many more, and
      that antigenically distinct 'mosaic' VSGs arise from segmental gene conversion
      between donor VSG genes or pseudogenes. The potential for trypanosome antigenic
      variation is probably much greater than VSG archive size; mosaic VSGs are core to
      antigenic variation and chronic infection. 

PMID- 23853605
TI  - Gastroesophageal reflux disease.

PMID- 23853604
TI  - Possible Mechanisms of Lymphoma Development in Sjogren's Syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a systemic as well as an organ-specific
      autoimmune disease characterized by lymphocytic infiltration of the glandular
      epithelial tissue. SS patients have been reported to be at highest risk of
      developing lymphoproliferative neoplasms, when compared with patients with other
      rheumatoid diseases. Factors such as cytokine stimulation, environmental factors,
      viral infection and genetic events as well as vitamin deficiency may contribute
      to the development of lymphoma. Over the past few decades, numerous efforts have
      been made to assess the relationship between lymphoma and SS. These include
      epidemiological surveys, molecular biologic assessments of clonality and well
      linked register cohort studies evaluating the predictive value of clinical,
      laboratory and histological findings. Nevertheless, the mechanisms and factors
      predictive of lymphoma development in pSS patients remain to be defined. This
      review summarizes updated knowledge on the incidence of and risk factors for
      lymphoma development in pSS patients, as well as discussing the most recent
      findings on the development and treatment of lymphoma in pSS patients and the
      possible mechanism of lymphoma development.

PMID- 23853606
TI  - Comparative in vitro effects of calcineurin inhibitors on functional vascular
      relaxations of both rat thoracic and abdominal aorta.
AB  - Background and Aim. Calcineurin inhibitors (CNIs) have shown to develop
      hypertension in transplant patients. The in vitro incubation effects of
      cyclosporine (CsA) and tacrolimus (Tac) on vascular relaxations of rat thoracic
      aorta (TA) and abdominal aorta (AA) need to be investigated. Methods. The optimal
      concentrations of CsA (1.0 mg/mL) and Tac (0.1 mg/mL) used to compare endothelium
      dependent (acetylcholine (ACh)) and endothelium-independent (sodium nitroprusside
      (SNP)) vascular relaxation against the agonists in phenylephrine (PE-)
      constricted TA and AA of 13-week-old male Sprague Dawley rats (n = 6). Results.
      In TA, the maximal vasodilator response elicited by ACh (control: I max 98%) was
      significantly (P < 0.01) inhibited by CsA (I max 10%) but not by Tac (I max 97%).
      In AA, (control: IC50 50 nM; I max 100%) CsA (IC50 7  MU M; (P < 0.01) showed
      strong sensitivity to inhibit ACh-dependent vascular relaxation than Tac (IC50
      215 nM (P < 0.05); I max 98%). CsA and Tac failed to affect the inhibitory
      responses to SNP in both TA and AA. Conclusion. CsA exerts profound inhibitory
      effect on endothelium-dependent vasodilatation as compared to Tac in both TA and
      AA. Aortic rings from the thoracic region are more sensitive to CNIs, since the
      vasodilator response to ACh is solely mediated by NO while in the AA, ACh likely
      recruits other endothelial mediators besides NO to maintain vasodilatation. 

PMID- 23853607
TI  - Determination of Tetracycline in Pharmaceutical Preparation by Molecular and
      Atomic Absorption Spectrophotometry and High Performance Liquid Chromatography
      via Complex Formation with Au(III) and Hg(II) Ions in Solutions.
AB  - UV-visible and atomic spectrophotometry and HPLC techniques were applied for the
      determination of tetracycline (TC) in pharmaceutical preparations via
      complexation of the drug with Au(III) and Hg(II) ions in solutions. The mole
      ratio of TC to metal ions was 1 : 1. Maximum peak absorption at lambda 425 and
      320 nm for the two ions, respectively, was optimized at heating temperature 75
      degrees C for 15 minutes at pH = 4 followed by the extraction with ethyl acetate.
      The percentage of extraction and stability constants for the two complexes was
      95.247, 95.335% and 2.518 * 10(4), 1.162 * 10(5) M(-1), respectively. HPLC method
      was applied without extraction process. The analytical data obtained from direct
      calibration curves of UV-visible absorption, FAAS, and HPLC for Au(III) complexes
      were recovery (100.78, 104.85, and 101.777%, resp.); detection limits (0.7403,
      0.0997, and 2.647  MU g/ml, resp.); linearity (5-70, 5-30, and 10-150  MU g/ml,
      resp.), and correlation coefficient (0.9991, 0.9967, and 0.9986, resp.). The
      analytical data obtained from direct calibration curves for Hg(II) complexes by
      UV-visible spectrophotometry and HPLC were recovery (100.95 and 102.000%, resp.);
      detection limits (0.5867 and 2.532  MU g/ml, resp.); linearity (5-70 and 10-150 
      MU g/ml, resp.); and correlation coefficients (0.9989 and 0.9997, resp.). 

PMID- 23853608
TI  - Ascaris lumbricoides: To Expect the Unexpected during a Routine Colonoscopy.
AB  - Ascaris lumbricoides is a common nematode infecting humans worldwide with
      increased prevalence in tropical and subtropical areas of less developed
      countries. Recently, it has been estimated that over one billion individuals are
      infected with ascariasis worldwide with 7% in USA. Although most of these cases
      are due to increasing immigration and travel outside America it is worth
      recognizing that prevalence of ascariasis is high in southeastern parts of USA
      due to their temperate climate. Infections of A. lumbricoides are largely
      asymptomatic, and hence a large population of people carrying this worm remains
      undetected for years until they develop some symptoms. Due to a large group of
      asymptomatic individuals with intestinal ascariasis, these worms are occasionally
      and unexpectedly identified during routine endoscopic procedures. Here, we
      present a case of an intestinal ascariasis found during routine colonoscopy in an
      African-American man from the Bronx with perianal itching. He denied any history
      of travel outside USA but reported frequent visits to South Carolina. This case
      illustrates the fact that ascariasis should be suspected even if immigration or
      travel outside USA is not involved. It should be suspected even in cases of
      travel within USA to the south east where endemic cases are reported. 

PMID- 23853609
TI  - Comparison of the direct effects of human adipose- and bone-marrow-derived stem
      cells on postischemic cardiomyoblasts in an in vitro simulated ischemia
      reperfusion model.
AB  - Regenerative therapies hold a promising and exciting future for the cure of yet
      untreatable diseases, and mesenchymal stem cells are in the forefront of this
      approach. However, the relative efficacy and the mechanism of action of different
      types of mesenchymal stem cells are still incompletely understood. We aimed to
      evaluate the effects of human adipose- (hASC) and bone-marrow-derived stem cells
      (hBMSCs) and adipose-derived stem cell conditioned media (ACM) on the viability
      of cardiomyoblasts in an in vitro ischemia-reperfusion (I-R) model. Flow
      cytometric viability analysis revealed that both cell treatments led to similarly
      increased percentages of living cells, while treatment with ACM did not (I-R
      model: 12.13 +/- 0.75%; hASC: 24.66 +/- 2.49%; hBMSC: 25.41 +/- 1.99%; ACM: 13.94
      +/- 1.44%). Metabolic activity measurement (I-R model: 0.065 +/- 0.033; hASC:
      0.652 +/- 0.089; hBMSC: 0.607 +/- 0.059; ACM: 0.225 +/- 0.013; arbitrary units)
      and lactate dehydrogenase assay (I-R model: 0.225 +/- 0.006; hASC: 0.148 +/-
      0.005; hBMSC: 0.146 +/- 0.004; ACM: 0.208 +/- 0.009; arbitrary units) confirmed
      the flow cytometric results while also indicated a slight beneficial effect of
      ACM. Our results highlight that mesenchymal stem cells have the same efficacy
      when used directly on postischemic cells, and differences found between them in
      preclinical and clinical investigations are rather related to other possible
      causes such as their immunomodulatory or angiogenic properties. 

PMID- 23853611
TI  - The health profile of populations living in contaminated sites: SENTIERI
      approach.
AB  - SENTIERI project (Epidemiological Study of Residents in Italian Contaminated
      Sites) studied mortality in the sites of national interest for environmental
      remediation (National Priority Contaminated Sites-NPCSs). SENTIERI described
      mortality of residents in NPCSSs, and it specifically focused on causes of death
      for which environmental exposure is suspected or ascertained to play an etiologic
      role. The epidemiological evidence of the causal association was classified a
      priori into one of these three categories: Sufficient (S), Limited (L), and
      Inadequate (I). Mortality in the period 1995-2002 was studied for 63 single or
      grouped causes at the municipal level by computing: crude rate, standardized
      rate, standardized mortality ratios (SMR), and SMR adjusted for an ad hoc
      deprivation index. Regional populations were used as references for SMR
      calculations and 90% CI accompanied SMR values. The deprivation index was
      constructed using 2001 national census variables for the following socioeconomic
      domains: education, unemployment, dwelling ownership, and overcrowding. SENTIERI
      results will allow the priorities setting in remediation intervention so as to
      prevent adverse health effects from environmental exposure. This paper's
      objective is to present the rationale, methods, advantages, and limitations
      underlying SENTIERI project and to describe data and resources required to apply
      a similar approach in other countries. 

PMID- 23853610
TI  - Immunomodulatory effects of mesenchymal stromal cells revisited in the context of
      inflammatory cardiomyopathy.
AB  - Myocarditis is a common inflammatory cardiomyopathy, associated with
      cardiomyocyte apoptosis, which can lead to chronic left ventricular dysfunction.
      Under conventional heart failure therapy, inflammatory cardiomyopathy typically
      has a progressive course, indicating a need for alternative therapeutic
      strategies to improve long-term outcomes. Experimental and clinical studies
      consistently support the application of cellular transplantation as a strategy to
      improve myocardial function. Mesenchymal stromal cells (MSCs) mediate distinct
      paracrine effects supporting endogenous regeneration, but most important are
      their remarkable immunoregulatory properties. In this review, an overview of
      current knowledge on immunopathology in myocarditis will be given. Furthermore,
      current research regarding the immunomodulatory properties of MSCs in the context
      of myocarditis will be discussed. Finally, the impact of MSC priming by the
      environment on their functionality and the advantages of systemic administration
      of MSCs under myocarditis are outlined. 

PMID- 23853612
TI  - Which one is more important, obesity or cardio metabolic risk factors?

PMID- 23853613
TI  - Serum leptin level is reduced in non-obese subjects with type 2 diabetes.
AB  - BACKGROUND: Leptin, a protein released from adipose tissue, could have
      significant role in pathogenesis of obesity and type 2 diabetes mellitus.
      OBJECTIVES: This study aimed to evaluate variations in serum leptin levels in non
      obese subjects with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: We
      studied forty-one patients with type 2 diabetes. Fasting lipid profile,
      Hemoglobin A1c (HbA1c), serum leptin, insulin, and glucose levels were measured
      by standard methods. RESULTS: The serum leptin level in type 2 diabetic patients
      (19.32 +/- 11.43 ng/mL) was significantly lower than that in non-diabetic
      subjects (32.16 +/- 11.02 ng/mL). Serum leptin level was strongly and positively
      correlated with body mass index (BMI) (r = 0.658, P < 0.0001) and calculated body
      fat percentage (r = 0.431, P < 0.0001) in all the study subjects with a better
      corrlation in the control subjcts compared to control cases (r = 0.661 for BMI
      and r = 0.466 for body fat). On the other hand, leptin showed a positive and
      significant correlation with insulin and HOMA- beta (homeostasis model assessment
      for beta-cell function) in both groups. Furthermore, leptin related to
      homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.422, P =
      0.006) was observed only in T2DM subjects. Leptin showed negative correlation
      with waist to hip ratio in diabetic (r = -0.407, P =0.008) and non-diabetic
      subjects (r = -0.318, P =0.049). In the regression model, BMI, HOMA-beta, and
      gender were independent predictors of leptin in all subjects. However, in non
      diabetic and diabetic subjects, beta-cell function and insulin were independent
      predictors, respectively (P =0.01). CONCLUSIONS: It is speculated that lower
      serum leptin levels in diabetic patients may be a consequence of male gender.
      Moreover, results suggest that serum leptin level in women is influenced
      differently than that in men.

PMID- 23853614
TI  - Value of exercise tolerance testing in evaluation of diabetic patients presented
      with atypical chest discomfort.
AB  - BACKGROUND: Coronary artery disease is the single most important cause of
      mortality and morbidity in diabetic patients. Electrocardiographic stress test is
      a non-invasive modality to screen significant coronary involvement in minimally
      symptomatic diabetics. OBJECTIVES: We investigated the Positive Predictive Value
      (PPV) of this test in comparison with coronary angiography. MATERIALS AND
      METHODS: 130 diabetic patients with atypical chest discomfort were studied and
      tested using Exercise Tolerance Test (ETT) among which 100 cases showed positive
      results that further were studied invasively by selective coronary angiography.
      RESULTS: The positive predictive value of ETT for diagnosis of Coronary Artery
      Disease (CAD)among diabetic patients presented with atypical chest discomfort was
      77%. CONCLUSION: We conclude that electrocardiographic stress test is a valuable
      inexpensive non-invasive screening test in diabetic patients with atypical chest
      discomfort.

PMID- 23853616
TI  - Number of components of the metabolic syndrome; smoking and inflammatory markers.
AB  - BACKGROUND: The association between inflammatory markers and the combination of
      the smoking status plus a number of components of the metabolic syndrome was not
      fully evaluated in male Japanese subjects. OBJECTIVES: To demonstrate the
      association between inflammatory markers and the number of components of the
      metabolic syndrome by considering smoking status. PATIENTS AND METHODS: A total
      of 3,017 male subjects (1,047 current smokers, 1,970 non-smokers) were included.
      Metabolic syndrome (MetS) was defined by the criteria of the National Cholesterol
      Education Program Adult Treatment Panel III. The smoking status was categorized
      in a binary manner into current smokers or non-smokers. RESULTS: The geometric
      mean value of the serum CRP increased linearly as the number of components of
      MetS increased (P < 0.05). In contrast, the mean values of the total WBC,
      neutrophil, lymphocyte and monocyte counts showed peak values when the number of
      MetS components was 3 or 4. The log-transformed serum CRP levels and the WBC
      counts were significantly correlated with one another (P < 0.001), but Pearson's
      correlation coefficient was under 0.3 for current smokers. CONCLUSIONS: Among
      several inflammatory markers, the serum CRP predominantly changed linearly as the
      number of MetS increased regardless of smoking status.

PMID- 23853615
TI  - The structure of metabolic syndrome components across follow-up survey from
      childhood to adolescence.
AB  - BACKGROUND: The choice of what parameters are needed for the diagnosis of
      Metabolic syndrome (MetS) has been criticized due to the lack of an actual "gold
      standard" diagnostic test even in adults. This problem seems to be greater in
      children and adolescents. OBJECTIVES: Stability assessment of factor structure
      underlying metabolic syndrome (MetS) components from childhood to adolescence in
      a panel study. PATIENTS AND METHODS: A total number of 643 (305 boys and 338
      girls) children (from 1999 to 2001), aged 6-10 years, with a complete median
      follow-up of 6.7 years (from 2006 to 2008) were selected among participants of
      Tehran Lipid and Glucose Study. We proposed 6 measured variables based on risk
      factors defined in Adult Treatment Panel III guidelines to describe clustering of
      MetS components. RESULTS: The Goodness of fit of the two-factor model, extracted
      from exploratory factor analysis, was appropriate for boys and girls in both
      stages of the study using confirmatory factor analysis. Systolic blood pressure
      (SBP) and triglycerides (TGs), with parameter estimates (PE) of 1 and 0.75,
      respectively, were the greatest risk factors at baseline in boys and girls. Waist
      circumference with PE of 0.88 and 0.62, and SBP with PE of 0.99 and 0.86 in
      adolescent boys and girls, respectively, were important risk factors.
      CONCLUSIONS: Our panel study supports the stability of the two-factor six
      variable model across two developmental stages from childhood to adolescence,
      among which adiposity, SBP, and TG were the predominant risk factors.

PMID- 23853617
TI  - Changes in serum leptin during phases of menstrual cycle of fertile women:
      relationship to age groups and fertility.
AB  - BACKGROUND: It is established that serum level of leptin is affected by
      transitional phases of reproduction. It is also reported that the puberty is
      triggered when body fat and circulating levels of leptin exceed the critical
      thresholds, butthere is less focus on the serum level of leptin and its
      relationship with different phases of menstrual cycle and the fertility.
      OBJECTIVES: The present study try to determines the serum concentration of leptin
      and fertility hormonesin the various phases of normal menstrual cycle of fertile
      women and compare any difference in serum concentration between age groups of 18
      30 years and 31-41 years It is a well known fact that fertility start to decrease
      from age 31 years. PATIENTS AND METHODS: A total of 118 healthy fertile women
      with normal menstrual cycle aged between 18-40, were divided into two age groups
      (n = 65) 18-30 years and (n = 53) 31-40 years. Serum concentrations of leptin,
      estradiol, progesterone, luteinising hormone (LH) and follicle-stimulating
      hormone (FSH) were measured on day1 (menstrual phase), day7
      (proliferative/follicular phase), day14 (ovulatory phase), day21 (luteal phase)
      and day 28(secretory phase) of the menstrual cycle. RESULTS: There was a
      significant increase (P < 0.05) in leptin levels on day 14 (12.75 + 5.8 ng/mL)
      and day 21 (12.91 + 3.2 ng/mL) for age group 18-30 years compared to day 14
      (11.60 + 3.2 ng/mL) and day 21 (11.60 + 3.2 ng/mL) for age group 31-40 years.
      Leptin was positively correlated with FSH on day 14, with LH on day 7 and day 21;
      likewise, with progesterone on day 21 and day 28 and with estradiol on day 7 and
      day 14 for both age groups. CONCLUSIONS: The serum leptin level was at the lowest
      level during the menstrual and secretory phase and the highest level was around
      the luteal phase. The significant increase ofleptin in the younger age group
      raise this question whether circulating leptin has any role to play in the age of
      pregnancy and fertility. Data in this study shows that leptin level was affected
      with increase in age; therefore changes in leptin level will affect fertility in
      this study suggest that there may be a relation between leptin levels and
      fertility.

PMID- 23853618
TI  - Temporal Changes in Plasma Concentration of Leptin, IGF-1, Insulin and
      Metabolites Under Extended Fasting and Re-Feeding Conditions in Growing Lambs.
AB  - BACKGROUND: A fall in plasma concentration of energy status related hormones
      (leptin, insulin-like growth factor-1 (IGF-1) and insulin) and body energy
      expenditure occurs in response to short term fasting. Nevertheless, the relations
      of the fasting-induced changes in energy related hormones and metabolites with
      fasting energy expenditure (FEE) under extended fasting condition have received
      little attention so far. OBJECTIVES: It is not clear how energy status related
      hormones coordinate to cope with feed deprivation under extended fasting time
      conditions and how quickly these hormones re-bound to fed-state values in
      response to re-feeding. Thus the objectives of this study were: 1) to determine
      the effects of extended fasting on plasma concentration of leptin, IGF-1,
      insulin, glucose, NEFA, 3-beta-hydroxybutyrate (BOHB) and urea; and 2) to study
      the relations of energy status related hormones with FEE and substrate oxidations
      under extended fasting conditions. MATERIALS AND METHODS: Eighteen six-month-old
      growing lambs (9 females and 9 males) were fasted for three days. Blood samples
      were taken one hour before (-1H) and 48 and 72 hours after fasting (48H and 72H)
      and two hours after re-feeding (+2H) from jugular vein. During the last 22 hours
      of fasting, gas exchange (CO2 production and O2 consumption) were measured using
      an open-circuit indirect calorimeter. Respiratory quotient (RQ), FEE and relative
      proportions of oxidized protein, fat and carbohydrate were calculated. RESULTS:
      Plasma levels of leptin, insulin, IGF-1 and glucose decreased but NEFA and urea
      levels increased within 48H of fasting. Concentration of insulin significantly
      increased with extended fasting while leptin and IGF-1 levels remained constant.
      Glucose was the only blood variable that showed a quick re-bound within two hours
      after re-feeding. Leptin and IGF-1 showed significant positive relations with
      glucose and BOHB but negative relations with NEFA and Urea. Carbohydrate, fat and
      proteins contributed to 17%, 61% and 22% of FEE respectively in three-day-fasted
      lambs. FEE was negatively correlated with insulin and NEFA concentrations in
      plasma. CONCLUSIONS: Even though plasma levels of leptin and IGF-1 decreased and
      remained constant under extended fasting, neither leptin nor IGF1 re-bounded to
      fed-status values within two hours after re-feeding. Under extended fasting
      condition, firstly an insulin resistance develops and secondly, a fall in FEE
      through a switch from carbohydrate- to fat-based metabolism occurs and there is
      an evident negative correlation between FEE and plasma concentration of NEFA.

PMID- 23853619
TI  - Non-contraceptive benefits of oral hormonal contraceptives.
AB  - It is becoming evident that oral hormonal contraceptives-besides being well
      established contraceptives-seem to become important medications for many
      functional or organic disturbances. So far, clinical effectiveness has been shown
      for treatment as well as prevention of menstrual bleeding disorders and menstrual
      related pain symptoms. Also this is true for premenstrual syndrome (PMS) and
      premenstrual disphoric disorder (PMDD). Particular oral contraceptives (OCs)
      containing anti-androgenic progestogens were shown to be effective medications
      for treatment of androgenisation symptoms (seborrhea, acne, hirsutism, alopecia).
      Through perfect suppression of the hypothalamic-pituitary-ovarian axis OCs have
      proven to be effective in elimination of persistent follicular cysts.
      Endometriosis/adenomyosis related pain symptoms are well handled similar to other
      drugs like Gonadotropine Releasing Hormone agonists but are less expensive, with
      less side effects, and possibility to be used for longer periods of time. This is
      also true for myoma. Pelvic inflammatory disease, rheumatoid arthritis, menstrual
      migraine, and onset of multiple sclerosis are prevented or delayed. Bone density
      is preserved and asthma symptoms improved. Endometrial hyperplasia and benign
      breast disease can be controlled. There is definitely a significant impact on
      risk reduction regarding endometrial, ovarian, and colon cancers. In conclusion,
      it needs to be recognized that oral combined hormonal contraceptives (estrogen/
      progestogen combination) are - besides being reliable forms of contraception -
      are cost-effective medications for many medical disorders in women. Therefore,
      these contraceptives drugs are important for female and global health and should
      be used in clinical practice. 

PMID- 23853620
TI  - Acute myocardial infarction secondary to catecholamine release owing to cocaine
      abuse and pheochromocytoma crisis.
AB  - Most pheochromocytomas are not suspected clinically while a high percentage of
      them are curable with surgery. We present the case of an adult cocaine-addicted
      male patient with an underlying pheochromocytoma and repeated myocardial
      infarctions. Computed tomography showed a left round adrenal mass, also high 24
      hour urine levels of catecholamines and metanephrines were detected from
      urinalysis. The patient was given alpha and beta blockers, moreover a
      laparoscopic left adrenalectomy was performed. Cocaine can block the reuptake of
      noradrenaline, leading to increasing its concentration and consequently its
      effects as well, and induce local or diffuse coronary vasoconstriction in normal
      coronary artery segments per se, cocaine can also trigger pheochromocytoma
      crisis, and therefore, cardiac complications such as myocardial infarction due to
      these additive effects are intended to occur. For this reason, in the presence of
      typical clinical manifestations of pheochromocytoma, such as sustained or
      paroxysmal hypertension, headache, sweating, tachycardia and abdominal pain,
      probable association of this tumor in patients with cocaine abuse and associated
      cardiac complications must be ruled out. 

PMID- 23853621
TI  - A Novel Medical Treatment of Cushing's Due to Ectopic ACTH in a Patient With
      Neurofibromatosis Type 1.
AB  - A 64-year-old male presented with neurofibromatosis 1 and Cushing's syndrome.
      Clinically he was over weight, depressed with extensive skin bruising and
      hypertension. His 24 hours urinary metanephrines, urinary 5HIAA, gut peptides and
      chromgranin levels were normal. His renal function and renal MRI scan was also
      normal. His cortisol failed to suppress on overnight dexamethsone suppression
      test. His low dose dexamethasone suppression with CRH stimulation showed failure
      of suppression of cortisol to < 50 nmol/L and ACTH was measurable at 10 ng/L on
      day 3. There was no response of ACTH or cortisol to CRH stimulation. His ACTH
      precursors were high at 126 pmol/L consistent with defective pro-opiomelanocortin
      (POMC) processing suggesting an ectopic source of ACTH production. The MRI scan
      of his pituitary and CT scan of the adrenal glands was normal. His octreotide
      scan was negative. The source of his ectopic ACTH was most likely a large
      retroperitoneal plexiform neurofibroma seen on CT abdomen that had undergone
      malignant peripheral nerve sheath tumour transformation on histology. He was a
      poor surgical risk for tumour debulking procedure. In view of the available
      literature and role of c-kit signalling in neurofibromatosis, he was treated with
      Imitinib. Four months after the treatment his Cushings had resolved on
      biochemical testing. After a year his plexiform neurofibroma has not increased in
      size. To our knowledge, this is the first case of NF1 associated with clinical
      and biochemical features of Cushing's secondary to ectopic ACTH due to MPNST in a
      plexiform neurofibroma and its resolution on treatment with imatinib. 

PMID- 23853623
TI  - Canola oil consumption and bone health.

PMID- 23853622
TI  - Evaluation of serum prolactin levels in intellectually disabled patients using
      antipsychotic medications.
AB  - BACKGROUND: Patients with intellectual disabilities may be treated with
      antipsychotic medications for a variety of diagnoses. Use of this category of
      medication can increase prolactin levels and place the patient at risk for sexual
      dysfunction and lower bone mineral density. The proposed mechanism of action is
      affinity for the dopamine receptor. Use of bromocriptine, a dopamine receptor
      antagonist, was proposed to attenuate hyperprolactinemia. OBJECTIVES: The
      objectives of this study were to (1) review serum prolactin (PRL) elevations
      associated with the use of antipsychotic (AP) medications in an intellectually
      disabled adult population and (2) determine if any association existed between
      the level of elevation and AP used. PATIENTS AND METHODS: Medical records for
      adult patients at two Oklahoma facilities for the intellectually disabled were
      reviewed to evaluate prolactin levels for individuals prescribed antipsychotics.
      A linear regression model was used to evaluate the relationship between prolactin
      levels with intellectual disability level, bromocriptine use, demographics, and
      antipsychotic. RESULTS: 73 (n = 53 males, n = 20 females) patients met criteria.
      The average age was 41.2 years. Nearly 70% of the patients had severe to profound
      levels of disability. 77% were prescribed second generation antipsychotics; 19%
      received first generation agents. Two variables, gender and bromocriptine use,
      were found to be significant predictors of prolactin levels. Mean prolactin level
      for females was 44 ng/mL (normal range: 4-30 ng/mL, males = 4-23 ng/mL). Patients
      who did not receive bromocriptine had mean levels of 23 ng/mL. No significant
      difference in prolactin levels was found for type of AP. CONCLUSIONS: Mean
      prolactin levels for females were significantly higher than for males. Both sexes
      were found to have higher-than-normal levels. Use of bromocriptine was associated
      with higher prolactin levels. In this population of patients, the type of AP used
      had no significance on prolactin levels.

PMID- 23853624
TI  - Mortality-related factors disparity among Iranian deceased children aged 1-59
      months according to the medical activities in emergency units: National mortality
      surveillance system.
AB  - BACKGROUND: To determine disparity in mortality-related factors in 1-59 months
      children across Iran using hospital records of emergency units. MATERIALS AND
      METHODS: After designing and validating a national questionnaire for mortality
      data collection of children 1-59 months, all 40 medical universities has been
      asked to fill in the questionnaires and return to the main researcher in the
      Ministry of Health and Medical Education. Age and sex of deceased children, the
      type of health center, staying more than 2 h in emergency unit, the reason of
      prolonged stay in emergency, having emergency (risk) signs, vaccination, need to
      blood transfusion, need to electroshock and so on have also been collected across
      the country. There was also a comparison of children based on their BMI. Chi
      square test has been applied for nominal and ordinal variables. ANOVA and t
      student test have been used for measuring the difference of continuous variables
      among groups. RESULTS: Mortality in 1-59 months children was unequally
      distributed across Iran. The average month of entrance to hospital was June, the
      average day was 16(th) of month, and the average hour of entrance to hospital was
      14:00. The average of month, day and hour for discharge was July, 16, and 14:00,
      respectively. The hour of discharge was statistically significant between
      children with and without risk signs. More than half (54%) of patients had
      referred to educational hospital emergency units. There were no statistically
      significant differences between children with and without emergency signs. There
      were statistically significant differences between children with and without
      emergency signs in age less than 24 months (0.034), nutrition situation (P =
      0.031), recommendation for referring (P = 0.013), access to electroshock
      facilities (P = 0.026), and having successful cardiopulmonary resuscitation (P =
      0.01). CONCLUSION: This study is one of the first to show the distribution of the
      disparity of early childhood mortality-related factors within a developing
      country. Our results suggest that disparity in 1-59 months mortality based on
      hospital records in emergency units needs more attention by policy-makers. It is
      advisable to conduct provincially representative surveys to provide recent
      estimates of hospital access disparities in emergency units and to allow
      monitoring over time.

PMID- 23853625
TI  - Dietary calcium intake and risk of obesity in school girls aged 8-10 years.
AB  - BACKGROUND: Some studies have demonstrated the role of calcium in reducing body
      mass index (BMI) or fat mass. Though, BMI does not provide very valid information
      about changes in body fat mass, Fat Mass Index (FMI) relates body fat mass to
      height and allows comparing body fat mass of individuals at different heights.
      This study investigated the possible association between dietary calcium intake
      (CI) and other nutritional factors and weight status of girls aged 8-10 years.
      MATERIALS AND METHODS: In this case-control study, 110 girls aged 8-10 with FMI
      at or above 7.2 kg/m(2) as cases and 307 girls with FMI less than 7.2 kg/m(2) as
      controls were recruited through multistage cluster random sampling. FMI at or
      above 7.2 kg/m(2) was considered as the cutoff point for obesity. Body fat mass
      was assessed by a stand on bio impedance analyzer. In order to assess CI,
      participants were asked to complete a validated food frequency questionnaire.
      RESULTS: Mean and standard deviation of CI in the case group was significantly
      lower than the control group 649 +/- 103 and 951 +/- 152 mg/d, respectively (P <
      0.01). After Adjustment for total energy intake, the percentage of energy from
      fat, carbohydrate and protein in quartiles of physical activity, inverse
      association between CI and obesity was significant and in the highest quartile of
      physical activity the association was weaker. By further adjustment for the
      effect of fruits and vegetable intake inverse association between CI and obesity
      became weaker but yet was significant. CONCLUSION: The inverse relationship
      between CI and FMI remained significant even after controlling for confounding
      factors. FMI may be more accurate, compared to BMI, in showing the association
      between CI and obesity.

PMID- 23853626
TI  - Evaluation of wet bulb globe temperature index for estimation of heat strain in
      hot/humid conditions in the Persian Gulf.
AB  - BACKGROUND: Heat exposure among construction workers in the Persian Gulf region
      is a serious hazard for health. The aim of this study was to evaluate the
      performance of wet bulb globe temperature (WBGT) Index for estimation of heat
      strain in hot/humid conditions by the use of Physiological Strain Index (PSI) as
      the gold standard. MATERIAL AND METHODS: This cross-sectional study was carried
      out on 71 workers of two Petrochemical Companies in South of Iran in 2010 summer.
      The WBGT index, heart rate, and aural temperature were measured by Heat Stress
      Monitor (Casella Microtherm WBGT), Heart Rate Monitor (Polar RS100), and Personal
      Heat Strain Monitor (Questemp II), respectively. The obtained data were analyzed
      with descriptive statistics and Pearson correlation analysis. RESULTS: The mean
      (SD) of WBGT values was 33.1 (2.7). The WBGT values exceed from American
      Conference of Governmental Industrial Hygienists (ACGIH) standard (30 degrees C)
      in 96% work stations, whereas the PSI values were more than 5.0 (moderate strain)
      in 11% of workstations. The correlation between WBGT and PSI values was 0.61 (P =
      0.001). When WBGT values were less and more than 34 degrees C, the mean of PSI
      was 2.6 (low strain) and 5.2 (moderate strain), respectively. CONCLUSION: In the
      Persian Gulf weather, especially hot and humid in the summer months, due to the
      WBGT values exceeding 30 degrees C (in 96% of cases) and weak correlation between
      WBGT and PSI, the work/rest cycles of WBGT Index is not suitable for heat stress
      management. Therefore, in Persian Gulf weather, heat stress evaluation based on
      physiologic variables may have higher validity than WBGT index.

PMID- 23853627
TI  - Weight loss and body composition changes following three sequential cycles of
      ketogenic enteral nutrition.
AB  - BACKGROUND: Ketogenic enteral nutrition (KEN) is a modification of the protein
      sparing modified fast in which a protein solution is introduced with a continuous
      infusion through a nasogastric tube over 10-days cycles. The aim of the study was
      to perform a retrospective analysis of the safety, compliance, weight loss and
      body composition changes after 3 sequential 10-days cycles of KEN therapy.
      MATERIALS AND METHODS: From a large number of patients who underwent KEN therapy
      in our department over a 5-year period, we selected 188 patients who participated
      in 3 KEN cycles with 10-13 days of break between them. Before and after the
      treatment cycles, body composition was analyzed by bioelectric impedance; a final
      assessment was made 10 days after the end of last cycle. During each rest period
      all the patients were on a low-carbohydrate, normal caloric diet. RESULTS: Most
      patients (97%) successfully tolerated the nasogastric treatment and lost an
      average of 14.4 kg of body weight, 10.6 kg of fat mass and 3.4 kg of body cell
      mass. Adverse effects were recorded as mild gastric hypersecretion (2%) and
      constipation (5%). Patients continued to lose fat during the 10-day follow up
      period after the end of each KEN Cycle. This effect may be explained by
      abnormality of water distribution during the rapid weight loss inducing the
      observed change in fat mass. CONCLUSION: Ten-days KEN treatment cycles can induce
      rapid weight loss and reduction of fat mass in obese patients. Furthermore,
      preservation of lean mass can be achieved by infusing 1.9 g of protein/kg of BCM.

PMID- 23853628
TI  - Relation of obesity with serum 25 hydroxy vitamin D3 levels in type 2 diabetic
      patients.
AB  - BACKGROUND: Hypovitaminosis D is associated with diabetes mellitus (DM). Aim of
      our study was to determine the relation of obesity with vitamin D levels in type
      2 diabetic patients. MATERIALS AND METHODS: We examined 101 type 2 diabetic
      patients and made a correlation analysis in all parameters. Then we classified
      our diabetics according to their body-mass indices and compared their 25 hdroxy
      vitamin D3 levels. RESULTS: We found negative correlation between 25O HD and body
      mass index (BMI) (P: <0.001, r: -0.23). When we classified our diabetics
      according to their body mass indices as normal, overweight and obese, and
      compared their 25 hydroxy vitamin D3 levels, we determined that in every BMI
      group 25 hydroxy vitamin D levels were not found to be significantly different.
      CONCLUSION: These results suggest that at least in a Turkish population with type
      2 DM vitamin D levels are low and correlate with BMI, but when vitamin D levels
      are so low, as obesity worsens vitamin D levels does not lessen.

PMID- 23853629
TI  - Aqueous concentrations of VEGF and soluble VEGF receptor-1 in diabetic
      retinopathy patients.
AB  - BACKGROUND: The aim of this study was to simultaneously measure the
      concentrations of vascular endothelial growth factor (VEGF) and soluble VEGF
      receptor-1 (sVEGFR-1, also known as sFlt-1) in the aqueous humor of patients with
      non-proliferative diabetic retinopathy (NPDR) and to investigate whether aqueous
      levels of vascular endothelial growth factor (VEGF) and VEGFR-1 are related to
      diabetic macular edema. MATERIALS AND METHODS: Aqueous humor was collected from
      27 diabetic patients and 33 age- and sex-matched normoglycemic controls and
      analyzed for pro-angiogenic VEGF and angiogenic inhibitor VEGFR-1 by enzyme
      linked immunosorbent assay (ELISA). The mean foveal thickness was measured by
      optical coherence tomography (OCT). RESULTS: There was no significant difference
      in the aqueous levels of VEGF in patients with NPDR compared with control
      subjects (P > 0.05), while the NPDR patients had significantly lower sVEGFR-1 in
      their aqueous humor. Furthermore, a significant (P < 0.01) positive correlation
      was observed between VEGF/sVEGFR-1 concentration and the mean foveal thickness
      measured on OCT. CONCLUSION: The results suggest that decreased chelating effect
      of sVEGFR-1 may be the preliminary event allowing VEGF to activate the
      proangiogenic endothelial cell state and to induce permeability. The imbalance
      between angiogenic agent (VEGF) and the antiangiogenic factors (sFlt-1), which is
      disturbed in the diabetic state, may determine the fate of diabetic macular
      edema.

PMID- 23853630
TI  - The effect of individual counseling, line follow-up, and free nicotine
      replacement therapy on smoking cessation in the samples of Iranian smokers:
      Examination of transtheoretical model.
AB  - BACKGROUND: According to transtheoretical model (TTM), Stage matched
      interventions are more effective in quitting. The objective of current study was
      to investigate the effect of individual counseling, line follow-up, and free
      nicotine replacement therapy (NRT) on smoking cessation in smokers who are in
      preparation stage of smoking. MATERIALS AND METHODS: In a randomized clinical
      trial design, through sending the short message system, potential participants in
      preparation stage of smoking were recruited and divided into control (n = 60)and
      treatment (n = 50) groups. The treatment group received an in-person counseling,
      line follow-up, and free NRT. TTM variables trend; pros and cons of smoking,
      behavioral and experiential processes, temptation, were assessed at baseline, 3
      and 6 months follow-up along with point prevalence and continuous abstinence.
      RESULTS: Continuous abstinence at 6-month follow-up were 3.3% (n = 2) in control
      group and 46% (n = 23) in the treatment group (x (2) = 34.041, P < 0.001). Time
      Chi group analyses indicated that except cons of smoking (P > 0.05), all TTM
      constructs had significantly changed; temptation (F = 36.864, P < 0.001), pros (F
      = 12.172, P < 0.001), experiential processes (F = 3.377, P < 0.001), and
      behavioral processes (F = 11.131, P < 0.001). CONCLUSION: Interventions based on
      TTM variables increased the quite rate in prepared and motivated people. Our
      findings suggest that interventions through individual counseling along with free
      NRT and line follow-up in people who prepare for quitting are beneficial for our
      country.

PMID- 23853631
TI  - Comparison of the effects of canola oil versus sunflower oil on the biochemical
      markers of bone metabolism in osteoporosis.
AB  - BACKGROUND: Recently, omega-3 fatty acids are in the center of attention for
      their potent anti-inflammatory effects. Osteoporosis as a chronic senile disease
      is associated with inflammation, and the role of inflammatory mediators has been
      demonstrated in the recent years. The beneficial effects of n-3 fatty acids on
      bone were proven in many animal studies, while to date, no conclusive data is
      available in human. The aim of this study was to evaluate the impact of n-3 fatty
      acids on bone biomarkers in osteoporotic women. MATERIAL AND METHODS: Forty
      osteoporotic post-menopausal women were recruited in the study and randomized in
      receiving either 40 g canola oil or the same amount sunflower oil per day as
      their dietary oil for 3 months. Serum levels of osteocalcin, bone alkaline
      phosphatase (BALP), N telo peptide collagen (NTX) and 25- hydroxy vitamin D3 were
      measured at baseline and at the end of the third month in both groups. RESULTS:
      In the canola oil group, BALP and NTX were increased after 3 months while
      Osteocalcin decreased in both groups slightly; however,none of these changes were
      significant. In both groups, serum vitamin D3 was increased significantly;
      however, this change between groups was not significant. CONCLUSION: Canola oil
      did not affect bone formation and resorption significantly after 3 months
      consumption. Further investigations with longer follow up are recommended.

PMID- 23853632
TI  - Exploring self care in Tehran, Iran: A population based study.
AB  - BACKGROUND: self care empowers individuals to self manage their minor ailments,
      chronic conditions, and to exert more control over their lives. Self care
      includes activities such as influencing prevention, health maintenance, and
      treatment of illness by individuals, this study was conducted to assess views
      about self care among the general population living in south of Tehran. MATERIALS
      AND METHODS: This survey was cross-sectional study by using of two-stage random
      cluster sampling, 1200 individuals aged 17 years and over was surveyed regarding
      self care. A structured closed validated questionnaire was used to collect data.
      Data were finally analyzed by Kruskal-Wallis, Pearson Chi-square, Fisher exact
      test and linear by linear association. Questionnaire has totally five parts
      including knowledge, attitude, performance toward self care, views regarding
      general health and demographic characteristics as well. Furthermore; project
      number is 4276-62-02-85. RESULTS: The mean age of subjects was 27.9 years (SD =
      5.2); 50.2% (n = 603) were female; 54% (n = 643) were married (deleted), (55%, n
      = 658) reported that they were not knowledgeable about self care and (82%, n =
      986) were interested in self care. Only 4% (n = 53) of subjects indicated they
      drank >= 7 glasses of water daily; fewer reported they consumed at least five
      portions of fruits/vegetables daily (3%, n = 31; and (4%, n = 51) engaged in
      physical activity more than 3 h weekly. There were statistically significant
      relationships between knowledge and interest (P < 0.01), knowledge and practice
      (P < 0.001), and interest and practice regarding self care (P < 0.001).
      CONCLUSION: The vast majority of subjects approximately two third felt satisfied
      with their health, most of subjects reported "feeling healthy" despite engaging
      in unhealthy life styles, it is revealed that more educated people, and likely
      those with more income, were interested in and knowledgeable regarding self care
      and were actually active in healthy life styles. In brief; this study suggests
      that physicians could support self care through their consultations with
      patients.

PMID- 23853633
TI  - Effect of mebudipine on oxidative stress and lipid peroxidation in myocardial
      ischemic-reperfusion injury in male rat.
AB  - BACKGROUND: Myocardial infarction (MI) is the acute condition of necrosis in
      myocardium which occurs as a result of imbalance between coronary blood supply
      and myocardial demand. The resultant oxidative stress excess leads to worsen the
      condition. The aim of this study was to investigate the effect of mebudipine, a
      new dihydropyridine calcium channel blocker, on lipid peroxidation and
      antioxidant enzymes in myocardial ischemia-reperfusion injury. MATERIALS AND
      METHODS: Male Wistar rats (250-300 g) were randomly divided to Control-ischemic,
      mebudipine-ischemic and vehicle (ethanol-ischemic) groups. The hearts of
      anaesthetized rats were removed and mounted on Langendorff apparatus and perfused
      by Krebs-Henseleit solution under constant pressure of 75 mmHg at 37 degrees C.
      Ischemic groups were received 30 min global ischemia and 120 min reperfusion and
      the mebudipine and vehicle groups received mebudipine (0.1 nM) or ethanol (0.01%)
      enriched solution 25 min before global ischemia. Malondialdehyde (MDA),
      superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase levels of
      heart tissue samples were determined by commercial specific Kits. RESULTS:
      Mebudipine significantly reduced the MDA level (2.3 +/- 0.07 nmol/mg protein) as
      the biochemical indicator of oxidative damage and lipid peroxidation product as
      compared with those of vehicle (4.6 +/- 0.01 nmol/mg protein) and control groups
      (4.8 +/- 0.09 nmol/mg protein). Furthermore, antioxidant enzymes SOD (0.1 +/-
      0.006 in drug vs. 0.037 +/- 0.009 U/mg Protein in control), GPX (16 +/- 0.009 in
      drug vs. 0.068 +/- 0.01 U/mg Protein in control) and catalase activities (0.075
      +/- 0.006 in drug vs. 0.028 +/- 0.002 U/mg Protein in control), activities of
      myocardium were significantly increased by mebudipine (P < 0.01). CONCLUSION: Our
      results showed that mebudipine may have antioxidant activity against myocardial
      ischemia-reperfusion injury since it decreased oxidative stress by enhancing the
      enzymatic antioxidant defense and inhibiting the lipid peroxidation. Thus, this
      drug can reduce the intensity of cardiac ischemic insults.

PMID- 23853634
TI  - Comparison of cerebral blood flow pattern by transcranial Doppler in patients
      with diffuse and focal causes of brain death.
AB  - BACKGROUND: This study aims to assess the cerebral vessels flow in brain death
      patients with different causes, including focal and diffuse lesions and
      comparison of flows according to the underlying causes. MATERIALS AND METHODS:
      Two groups of 15 brain-dead patients one with focal and the other with diffuse
      brain lesions were compared according to their cerebral blood flow pattern 48 h
      passed brain death certification. RESULTS: Bilateral absence of flow in middle
      cerebral artery (MCA) was found in 54.5% of brain-dead patients with diffuse
      lesion and 50.33% of those with focal lesions. Systolic spike pattern in MCA flow
      was found in 46.2% of patients with focal lesion and 16.65% of patients with
      diffuse lesion. Diastole-systole separation pattern in MCA was seen in 16.65% of
      patients with the diffuse lesions. This pattern in MCA was not seen in patients
      with the focal lesion group. In carotid arteries, we did not find the absence of
      flow in any cases. Thirty percent of all patients in both groups had a normal
      flow pattern (36.6% of patients with focal lesions and 23.3% of patients with
      diffuse lesion). Patients with focal lesion had 33.3% systolic spike pattern flow
      and had 23.35% diastole-systole separation flow pattern. In intra-cranial
      vessels, systolic spike pattern was more common among patients with focal lesions
      than patients with diffuse lesion, however, this difference was not statistically
      significant (46.2% of patients with focal lesion and 16.65% of patients with
      diffuse lesion) (P value = 0.244-0.09). Diastole-systole separation flow was more
      common in patients with diffuse lesions than those with the focal lesions
      although this could not reach the significant level as the previous pattern (20%
      of patients with diffuse lesion versus no case in patients with focal lesion) (P
      value = 0.181). CONCLUSION: Absence of flow was the most common brain flow
      pattern in the focal and diffuse group lesions. There was no difference in flow
      pattern between the focal and diffuse brain lesions groups in brain-dead
      patients.

PMID- 23853635
TI  - The effect of magnesium supplementation on primary insomnia in elderly: A double
      blind placebo-controlled clinical trial.
AB  - BACKGROUND: Nearly 50% of older adults have insomnia, with difficulty in getting
      to sleep, early awakening, or feeling unrefreshed on waking. With aging, several
      changes occur that can place one at risk for insomnia, including age-related
      changes in various circadian rhythms, environmental and lifestyle changes, and
      decreased nutrients intake, absorption, retention, and utilization. The natural N
      methyl-D-aspartic acid (NMDA) antagonist and GABA agonist, Mg(2+), seems to play
      a key role in the regulation of sleep. The objective of this study was to
      determine the efficacy of magnesium supplementation to improve insomnia in
      elderly. MATERIALS AND METHODS: A double-blind randomized clinical trial was
      conducted in 46 elderly subjects, randomly allocated into the magnesium or the
      placebo group and received 500 mg magnesium or placebo daily for 8 weeks.
      Questionnaires of insomnia severity index (ISI), physical activity, and sleep log
      were completed at baseline and after the intervention period. Anthropometric
      confounding factors, daily intake of magnesium, calcium, potassium, caffeine,
      calories form carbohydrates, and total calorie intake, were obtained using 24-h
      recall for 3 days. Blood samples were taken at baseline and after the
      intervention period for analysis of serum magnesium, renin, melatonin, and
      cortisol. Statistical analyses were performed using SPSS19 and P values < 0.05
      were considered as statistically significant. RESULTS: No significant differences
      were observed in assessed variables between the two groups at the baseline. As
      compared to the placebo group, in the experimental group, dietary magnesium
      supplementation brought about statistically significant increases in sleep time
      (P = 0.002), sleep efficiency (P = 0.03), concentration of serum renin (P <
      0.001), and melatonin (P = 0.007), and also resulted in significant decrease of
      ISI score (P = 0.006), sleep onset latency (P = 0.02) and serum cortisol
      concentration (P = 0.008). Supplementation also resulted in marginally between
      group significant reduction in early morning awakening (P = 0.08) and serum
      magnesium concentration (P = 0.06). Although total sleep time (P = 0.37) did not
      show any significant between-group differences. CONCLUSION: Supplementation of
      magnesium appears to improve subjective measures of insomnia such as ISI score,
      sleep efficiency, sleep time and sleep onset latency, early morning awakening,
      and likewise, insomnia objective measures such as concentration of serum renin,
      melatonin, and serum cortisol, in elderly people.

PMID- 23853636
TI  - What variables can influence clinical reasoning?
AB  - BACKGROUND: Clinical reasoning is one of the most important competencies that a
      physician should achieve. Many medical schools and licensing bodies try to
      predict it based on some general measures such as critical thinking, personality,
      and emotional intelligence. This study aimed at providing a model to design the
      relationship between the constructs. MATERIALS AND METHODS: Sixty-nine medical
      students participated in this study. A battery test devised that consist four
      parts: Clinical reasoning measures, personality NEO inventory, Bar-On EQ
      inventory, and California critical thinking questionnaire. All participants
      completed the tests. Correlation and multiple regression analysis consumed for
      data analysis. RESULTS: There is low to moderate correlations between clinical
      reasoning and other variables. Emotional intelligence is the only variable that
      contributes clinical reasoning construct (r=0.17-0.34) (R(2) chnage = 0.46, P
      Value = 0.000). CONCLUSION: Although, clinical reasoning can be considered as a
      kind of thinking, no significant correlation detected between it and other
      constructs. Emotional intelligence (and its subscales) is the only variable that
      can be used for clinical reasoning prediction.

PMID- 23853637
TI  - Conjunctival biopsies and ophthalmic lesions: A histopathologic study in eastern
      India.
AB  - BACKGROUND: The conjunctiva is a thin and flexible mucus membrane that provides a
      protective barrier to the eye. Very few histopathologic studies have been
      conducted on conjunctival biopsies in eastern India. MATERIALS AND METHODS: 120
      conjunctival biopsies from 117 patients (76 males, 41 females) received during 8
      years (January 2003-December 2010) were included in this study. RESULTS:
      HISTOLOGIC DIAGNOSES WERE: degenerative lesions in 38 cases (31.66%), benign
      epithelial lesions in 23 cases (19.16%), premalignant and malignant epithelial
      lesions in 27 cases (22.5%), melanocytic lesions in 10 cases (8.33%), lymphoid in
      7 cases (5.83%), and miscellaneous in 15 cases (12.5%). CONCLUSION: Squamous
      papilloma was the commonest benign tumor, whereas the commonest malignant tumor
      was squamous cell carcinoma. Melanocytic lesions were less prevalent compared to
      other/western studies.

PMID- 23853638
TI  - Protocol: Effect of intravitreal bevacizumab (avastin) in the treatment of
      macular edema: A systematic review of randomized controlled trials.
AB  - Cystoid macular edema (CME) is a relatively common painless condition usually
      accompanied by blurred vision. The prevalence of CME varied from 5% to 47%
      depending on cause of pathology. There are several treatments available for ME
      including intravitreal use of bevacizumab that has been used in different doses
      in few studies. However, there is still scarcity of data available on the use of
      bevacizumab for the treatment of ME. A systematic review is needed to provide a
      foundational base to discuss and synthesize the available information on the
      effectiveness and safety of intravitreal bevacizumab in macular edema, so that
      recommendations and policies can be built regarding controversial use of
      bevacizumab in macular edema. We have planned to perform a systematic review with
      an objective to compare the effects of a single injection of 1.25 mg intravitreal
      bevacizumab (avastin) in the improvement of visual acuity, macular edema, and
      thickness with other interventions/controls for the treatment of macular edema at
      3 and 6 months interval using randomized controlled trials. This is only a
      protocol of the review and we will be conducting a full length review, addressing
      the issue in future. 

PMID- 23853639
TI  - Bilateral breast swelling in a 23-year-old woman with Burkitt lymphoma.
AB  - Primary breast lymphoma (PBL) of the breast is a rare type of localized non
      Hodgkin lymphoma, which is usually of the B-cell. The majority of breast lymphoma
      present as a unilateral painless breast masses in an older woman, average age at
      diagnosis 55-60. A less common but distinctive presentation is a young woman of
      childbearing age who presents during or immediately after pregnancy. We present a
      23-year-old postpartum woman with bilateral breast swelling. After surgical
      drainage and debridement and pathologic examination, the diagnosis of breast
      Burkitt lymphoma (BL) was confirmed. Chemotherapy was immediately started for her
      and the patient showed a good response with complete remission. 

PMID- 23853640
TI  - Primary aneurysmal bone cyst of talus.
AB  - Aneurysmal bone cyst (ABC) of the talus is an extremely rare lesion; less than 20
      cases have been reported in PubMed till 2012. We report a primary ABC of the
      talus in a 20-year-old male that was managed by extended intralesional curettage
      with phenol as an adjuvant and autologous cancellous iliac crest bone grafting.
      The patient had excellent functional outcome and there was no recurrence at 2
      years of follow-up. 

PMID- 23853641
TI  - Recommendations for patients with diabetes mellitus during hajj pilgrimage.

PMID- 23853642
TI  - Visual impairment screening program among pre-school children in Hamadan.

PMID- 23853643
TI  - Ginger as a miracle against chemotherapy-induced vomiting.
AB  - BACKGROUND: Vomiting is one of the most prevalent side effects of chemotherapy in
      cancer patients. The aim of this study was to evaluate the effect of ginger plant
      on chemotherapy-induced vomiting, since the previous studies were somehow
      imperfect and have provided controversial results. MATERIALS AND METHODS: This
      randomized double-blind placebo-controlled clinical trial was conducted on 80
      women with breast cancer undergoing chemotherapy and suffering from vomiting in
      Imam Khomeini Hospital, Tehran, Iran, between July and December 2009. During a
      convenience sampling the participants were randomly allocated into treatment and
      placebo groups after taking a written informed consent. Two groups were matched
      based on the age and emetic risk of chemotherapy drugs. The treatment group
      received 250 mg ginger powder capsules (Zintoma) and placebo group 250 mg starch
      capsules 4 times a day (1 g/day) for 6 days since 3 days before chemotherapy
      session. A two-part self-made questionnaire was used to assess the effect of
      ginger. Patients completed the instrument every day. Then by STATA software
      version 8, the gathered data were analyzed using Fisher's exact, Kruskal-Wallis,
      and Chi-square tests. RESULTS: The 2 groups had no significant age differences
      and were matched (ginger: 41.8+/-8.4 vs placebo: 45.1+/-10, P = 0.1). Vomiting
      cases were significantly lower in ginger group at anticipatory (P = 0.04), acute
      (P = 0.04), and delayed (P = 0.003) phases. Also, heartburn was the only and
      venial reported side effect (P > 0.05). CONCLUSIONS: Taking ginger capsules (for
      6 days since 3 days before chemotherapy) accompanied by the routine antiemetic
      treatment could relieve chemotherapy-induced vomiting in all phases.

PMID- 23853644
TI  - Passing through a rocky way to reach the pick of clinical competency: A grounded
      theory study on nursing students' clinical learning.
AB  - BACKGROUND: Clinical learning is one of the important issues that helps the
      perception of nursing students' practice in a clinical setting and its effect on
      their professional development. The aim of this study is to describe and state
      the manner of clinical learning in nursing students. MATERIALS AND METHODS: This
      qualitative study was conducted as a grounded theory. The individual semi
      structured interviews and participants' observations were taken into account with
      a purposive and theoretical sample of 27 participants. The data were analyzed
      using the grounded theory approach and the constant comparison analysis method.
      RESULTS: The results showed that students use two approaches of Micro- and
      Macrolearning. The first includes learning conditions and situations that act
      like a foundation for the second one (Macrolearning). Macrolearning is a
      continuous process including all categories of "Facing unfavorable clinical
      facts", "Clinical situation and appropriate decision making", "Bridging the gap
      between practice and theory", "Struggle for clinical independence", and
      "Dynamism" in a continuum reflecting the struggle to obtain clinical competency
      (core variable). CONCLUSIONS: Through provision of such conditions as students'
      gradual acquaintance with real situations, selection of more resistant students,
      use of mentorship and preceptor ship in clinical learning, enhancement of
      educational standards in hospitals, handling collaborative learning methods to
      make a cooperation spirit in internship environment, and so on, students can be
      helped to obtain clinical competency.

PMID- 23853645
TI  - The effect of nursing consultation involving cancer survivors on newly diagnosed
      cancer patients' quality of life.
AB  - INTRODUCTION: Cancer and its treatments have a significant effect on the Quality
      of Life (QoL) of people who suffer from cancer. Nursing consultation involving
      cancer survivors might be beneficial for other patients as they successfully
      managed and lived with cancer. But controversies still exist in the research
      findings as how nursing consultation involving cancer survivors might influence
      other cancer patients' QoL. Therefore, a research study was done to determine the
      effect of nursing consultation with the presence of cancer survivors on cancer
      patients' QoL. MATERIALS AND METHODS: The study was a quasi-experimental research
      using a pre-post test design, which was conducted in Sayyed- AL-Shohada Hospital
      affiliated to Isfahan University of Medical Sciences, Iran, in 2010. Twenty-two
      adult patients who suffered from acute leukemia who were receiving chemotherapy
      were selected. They participated in a nursing consultation group in which cancer
      survivors were actively engaged. The patients' QoL was assessed before, 1 week,
      and 1 month after the nursing consultation using the European Organization for
      Research and Treatment of Cancer Quality of Life Core-30 Version 3 (EORTC QLQ-C30
      V3) questionnaire. RESULTS: Comparing QoL mean scores of patients in the symptom,
      performance, and the general health status scales showed that there was not any
      significant change in the QoL scores before, 1 week, and 1 month after the
      consultation. CONCLUSION: It seems that the nursing consultation with the
      presence of cancer survivors couldn't enhance patients' QoL, although it might
      prevent worsening the patients' QoL. Cancer has deleterious impacts on patients'
      QoL and nursing consultation may not improve QoL in a short period of time. It is
      recommended that the study be conducted with a larger sample, in a longer time
      and with a case-control design.

PMID- 23853646
TI  - Spirituality in survivors of myocardial infarction.
AB  - BACKGROUND: Life-threatening and stressful events, such as myocardial infarction
      (MI) can lead to an actual crisis, which affects the patients spiritually as well
      as physically, psychologically, and socially. However, the focus of health care
      providers is on physical needs. Furthermore, the spirituality of the patients
      experiencing heart attack in the light of our cultural context is not well
      addressed in the literature. This study is aimed at exploring the spiritual
      experiences of the survivors of the MI. MATERIALS AND METHODS: In this
      qualitative research a grounded theory approach was used. Key informants were 9
      MI patients hospitalized in the coronary care units of 3 hospitals in Shiraz. In
      addition, 7 nurses participated in the study. In-depth interviews and a focus
      group were used to generate data. Data analysis was done based on Strauss and
      Corbin method. Constant comparison analysis was performed until data saturation.
      RESULTS: Five main categories emerged from the data, including perceived threat,
      seeking spiritual support, referring to religious values, increasing faith, and
      realization. The latter with its 3 subcategories was recognized as core category
      and represents a deep understanding beyond knowing. At the time of encountering
      MI, spirituality provided hope, strength, and peace for the participants.
      CONCLUSION: Based on the results we can conclude that connecting to God,
      religious values, and interconnectedness to others are the essential components
      of the participants' spiritual experience during the occurrence of MI.
      Spirituality helps patients to overcome this stressful life-threatening
      situation.

PMID- 23853647
TI  - Nurses' perception of occupational stress and its influencing factors: A
      qualitative study.
AB  - BACKGROUND: Studies have shown that nurses are under considerable job stress,
      which can lead to health disorders and failure in duties. Stressors of nursing
      have been studied in some of quantitative studies; however, a few investigators
      have studied the nurses' life experiences in this regard. The current qualitative
      research aimed to understand the nurses' experiences and perceptions of job
      related stress. MATERIALS AND METHODS: This qualitative study was conducted in
      2010-2011 by using the content analysis technique. Data were collected through
      individual deep interviews with 19 nurses working in hospitals affiliated to
      Kashan University of Medical Sciences. The content of data was analyzed by the
      Krippendorff method. RESULTS: Three categories were emerged including 'nurses'
      perception from the job stress, "professional interest", and "prioritizing career
      over family life". The first category included the following subcategories of
      "being in constantly alarm situation," "lack of experience", "dignity and social
      status", "lack of proper logistics", "shortage of nurses", "Irregularities in the
      organization," "directors of nursing performance," "undesirable relations among
      colleagues," and "the patients conditions all have effects on the nurses' level
      of professional stress. CONCLUSION: The study participants defined job stress as
      a condition in which a nurse is under pressure so that the quality of care and
      the nurses' personal and family life is interrupted. Being under continuous
      pressure, low social dignity, and the manner of nurse managers were among the
      important sources of job stress. Providing appropriate logistics, improving the
      coordination within hospital subsystems, and improving the managers and nurses
      relationships may decrease the stressors in nursing profession.

PMID- 23853648
TI  - A comparison of face to face and video-based education on attitude related to
      diet and fluids: Adherence in hemodialysis patients.
AB  - INTRODUCTION: Adherence to diet and fluids is the cornerstone of patients
      undergoing hemodialysis. By informing hemodialysis patients we can help them have
      a proper diet and reduce mortality and complications of toxins. Face to face
      education is one of the most common methods of training in health care system.
      But advantages of video- based education are being simple and cost-effective,
      although this method is virtual. MATERIALS AND METHODS: Seventy-five hemodialysis
      patients were divided randomly into face to face and video-based education
      groups. A training manual was designed based on Orem's self-care model. Content
      of training manual was same in both the groups. In the face to face group, 2
      educational sessions were accomplished during dialysis with a 1-week time
      interval. In the video-based education group, a produced film, separated to 2
      episodes was presented during dialysis with a 1-week time interval. An Attitude
      questionnaire was completed as a pretest and at the end of weeks 2 and 4. SPSS
      software version 11.5 was used for analysis. RESULTS: Attitudes about fluid and
      diet adherence at the end of weeks 2 and 4 are not significantly different in
      face to face or video-based education groups. The patients' attitude had a
      significant difference in face to face group between the 3 study phases (pre-, 2,
      and 4 weeks postintervention). The same results were obtained in 3 phases of
      video-based education group. CONCLUSION: Our findings showed that video-based
      education could be as effective as face to face method. It is recommended that
      more investment be devoted to video-based education.

PMID- 23853649
TI  - Role of Benzodiazepines in the management of agitation due to inappropriate use
      of naltrexone.
AB  - BACKGROUND: Agitation is an early symptom of the acute opioid withdrawal syndrome
      in addicts that may start by inappropriate use of naltrexone. The current drug
      interventions are not efficient or need critical care as well. This study
      compares the clinical role of midazolam and diazepam for the management of
      agitation due to inappropriate use of naltrexone. MATERIALS AND METHODS: In this
      double-blind randomized controlled clinical trial, 44 agitated addicts, who did
      not use any type of benzodiazepine, not on systematic central nervous system
      depressant drugs, without any known hypersensitivity to diazepam, midazolam, or
      any other component of their formulation and had no evidence for the need of
      critical care, were enrolled. An i.v. stat dose of 0.1 mg/kg diazepam and 0.1
      mg/kg stat dose of midazolam and a 0.1 mg/kg/h infusion of these drugs were
      administered for different groups of patients, respectively. Agitation scores
      were recorded at 30, 60, 120 min after the start of drug administration using
      Richmond Agitation Sedation Scale score. RESULTS: A significant difference
      between the mean onset of agitation control in midazolam group (at 67 min) and
      diazepam group (at 81 min) was recorded. The difference of mean agitation score
      in the midazolam and diazepam group was only significant at 120 min. There was a
      negative correlation between agitation score and time elapsed from naltrexone
      administration to admission. CONCLUSION: Midazolam and diazepam may not be
      considered suitable and perfect pharmacologic agents for the initial controlling
      of agitation induced by naltrexone.

PMID- 23853650
TI  - How public perceive diabetes: A qualitative study.
AB  - BACKGROUND: Diabetes has a high prevalence in Iran, and its incidence is
      estimated to increase from 3.5 million adults in 2005 to 5.1 million by 2025.
      Given the high prevalence of diabetes in Iranians, it is surprising that little
      is known about understanding of diabetes in the general population. This study
      aimed to explore how people without diabetes interpreted the disease. MATERIALS
      AND METHODS: This study was conducted as a qualitative content analysis, using
      unstructured and in-depth interviews, with the participation of 21 individuals
      without diabetes (13 women and 8 men), 18-61 years old, who were selected for
      this purpose from the cities of Isfahan and Tehran from October 2010 to May 2011.
      The data were analyzed using latent content analysis method. RESULTS: The
      participants had different beliefs and ideas about diabetes and most of them gave
      a negative and black image of diabetes. Although a small number of individuals
      considered diabetes better than AIDS and cancer, they often took diabetes as
      blackness, end of romances, and a gradual death. CONCLUSION: However, the study
      sample was small. The findings show that the participants' perspective on
      diabetes is negative and destructive. It seems shaping a new identity in the path
      of empowerment could be difficult within the social and cultural context. These
      findings can give an insight to health care providers to realize how important it
      is to find the public perception about diabetes. They are responsible to change
      or modify the public view on diabetes by introducing the disease with the help of
      prominent people and educating individuals in the society on all aspects of
      living with diabetes, not simply the symptoms and disabilities it brings along.

PMID- 23853651
TI  - Comparison of nursing students' and clinical nurses' attitude toward the nursing
      profession.
AB  - BACKGROUND: To develop nursing education and promote nursing strategies, there is
      a need for a staff with positive attitude. The present study was conducted to
      compare the attitudes among clinical nurses and nursing students toward the
      nursing profession. MATERIALS AND METHODS: In this descriptive- analytical study
      313 clinical nurses and 81 nursing students (total n = 394) of Tehran, Iran, were
      selected through a systematic sampling method and their viewpoints were
      investigated using a nursing professional attitude questionnaire. RESULTS: The
      findings of this study showed that 72.6% of nurses and 65.4% of students had
      positive attitude toward their profession, and despite the high percentage of the
      clinical nurses' positive outlook, the difference was not statistically
      significant (P > 0.05). CONCLUSION: The results showed that approximately one
      third of the students and nursing practitioners had neutral or negative attitude
      toward their occupation. Due to the serious effect of one's professional attitude
      and commitment of service, it is necessary to have further studies about the
      current situation to eliminate such negative factors.

PMID- 23853652
TI  - Gender differences in risk factors of obese patients after cardiac rehabilitation
      program.
AB  - BACKGROUND: Obesity is common in patients with cardiovascular disease (CVD) and
      the vast majority of patients entering into cardiac rehabilitation program (CRP)
      are obese. Regarding the gender differences, the risk of developing coronary
      heart disease (CHD) is recognized to be different between obese men and women.
      So, the purpose of this study was to explore the effect of CRP in functional
      capacity (FC) and risk factors, such as obesity indexes, lipid profiles, and
      fasting blood sugar (FBS) in obese men and women with CHD. MARTERIALS AND
      METHODS: In an observational study between 2000 and 2011, we evaluated a total of
      156 obese men and women patients with CHD who were referred to cardiac
      rehabilitation of Isfahan Cardiovascular Research Institute. Before and after
      CRP, FC and risk factors were assessed and all the participants completed this
      period. Data were analyzed with SPSS software version 15. For comparing the mean
      of outcomes, independent t tests and paired sample t tests were used. RESULTS:
      Data revealed, after CRP, obese women had significant improvement in most
      evaluated risk factors except total cholesterol (P = 0.05) and FBS (P = 0.09);
      and obese men had favorable changes in weight (P = 0.00) and body mass index (P =
      0.00), FC (P = 0.00) and total cholesterol (P = 0.02); in spite of no significant
      differences in other lipid profiles. Comparing the 2 groups did not show any
      significant differences unless high-density lipoprotein cholesterol (P = 0.01)
      and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol
      ratio (P = 0.02) had greater improvement in obese women. CONCLUSION: We concluded
      that CRP is an important step initiating the process of risk reduction and
      restoration of FC in obese men and obese women with CHD under attendance and
      supervision of physician, nurse, and exercise physiologist.

PMID- 23853653
TI  - Differentials in colostrum feeding among lactating women of block RS Pura of J
      and K: A lesson for nursing practice.
AB  - BACKGROUND: Breast feeding is universally and traditionally practicised in India.
      Experts advocate breast feeding as the best method of feeding young infants.
      OBJECTIVE: To assess the role of various factors in determining colostrum feeding
      in block R. S. Pura of district Jammu. MATERIALS AND METHODS: A stratified two
      stage design with villages as the primary sampling unit and lactating mothers as
      secondary sampling unit. Villages were divided into different clusters on the
      basis of population and sampling units were selected by a simple random
      technique. RESULTS AND CONCLUSION: Breastfeeding is almost universal in R. S.
      Pura. Differentials in discarding the first milk were not found to be important
      among various socioeconomic groups and the phenomenon appeared more general than
      specific.

PMID- 23853654
TI  - Internal motivations and barriers effective on the healthy lifestyle of middle
      aged women: A qualitative approach.
AB  - BACKGROUND: A healthy lifestyle is one of the basic health-promotion strategies.
      Several factors are involved in shaping health-promotion behaviors. The internal
      barriers are the opinion and feelings that surround the individual and are the
      reasons that complicate the change of behavior. The aim of this study was to
      identify internal motivations and barriers effective on the healthy lifestyle in
      middle-aged Iranian women. MATERIALS AND METHODS: This was a qualitative study
      based on content analysis of in-depth semi-structured interviews with 21 middle
      aged women in the city of Yazd, who were selected using purposeful sampling
      approach. The interviews continued until data saturation was reached; and the
      interviews were audio-recorded and transcribed exactly. The transcripts were
      analyzed. RESULTS: FIVE MAIN THEMES EMERGED FROM THE ANALYSIS OF THE INTERVIEWS:
      Women's knowledge of health-promoting behaviors, importance of health and healthy
      behavior of women, affliction or fear of affliction to chronic disease and its
      consequences, responsibilities of women in the family and society, and skills of
      life management in women. CONCLUSION: The findings suggest that empowering
      individual participants in health promotion is the most important factor
      determining their health. Thus, designing appropriate programs for education and
      empowerment of people is essential to promoting health. Health policy makers,
      with knowledge of these factors, can design comprehensive, socialization programs
      to promote women's health.

PMID- 23853655
TI  - Novel antidepressant-like activity of propolis extract mediated by enhanced
      glucocorticoid receptor function in the hippocampus.
AB  - Propolis is a natural product made by honeybees that has been widely used in folk
      medicine with a broad spectrum of biological activities. To investigate the
      antidepressant-like activity of propolis extract, CD-1 mice were administered an
      ethanol extract of propolis (50, 100, or 200 mg/kg, p.o.) prior to the behavioral
      test. The propolis extract-treated group showed a dose-dependent decrease in
      immobility time in the FST and tail suspension test without altering locomotor
      activity. Propolis extract decreased the limbic hypothalamic-pituitary-adrenal
      axis response to the FST as indicated by an attenuated corticosterone response
      and decreased in c-fos immunoreactive neurons in the hippocampal dentate gyrus.
      Western blot analysis revealed a reduction in hippocampal glucocorticoid receptor
      (GR) expression following the FST, which was reversed by propolis extract.
      Propolis extract also increased pGR(S220)/(S234) ratio by a differential
      phosphorylation in S220 and S234. FST-induced downregulation of cAMP-responsive
      element binding protein phosphorylation at S133 (pCREB) was restored by propolis
      extract, showing a strong and positive relationship between pCREB and
      pGR(S220)/(S234) ratio. These findings suggest that the propolis extract
      potentiates antidepressant-like activity by enhancing GR function which is one of
      the therapeutic mechanisms of antidepressant; thus, propolis extract may provide
      a novel therapy for depression. 

PMID- 23853656
TI  - Preventive Effects of a Natural Anti-Inflammatory Agent, Astragaloside IV, on
      Ischemic Acute Kidney Injury in Rats.
AB  - This study investigated the anti-inflammatory effects of astragaloside IV(AS-IV)
      on ischemia/reperfusion (IR) induced acute kidney injury (AKI) in rats.
      Experimental model of ischemic AKI was induced in rats by bilateral renal artery
      clamp for 45 min followed by reperfusion of 12 h and 24 h, respectively. AS-IV
      was orally administered once a day to rats at 10 and 20 mg.kg(-1).d(-1) for 7
      days prior to ischemia. AS-IV pretreatment significantly decreased serum urea,
      creatinine, and cystatin C levels at 12 h and 24 h of reperfusion in AKI rats. AS
      IV pretreatment also ameliorated tubular damage and suppressed the
      phosphorylation of p65 subunit of NF- kappa B in AKI rats. Moreover, NF- kappa B
      and MPO activity as well as serum and tissue levels of TNF- alpha , MCP-1, and
      ICAM-1 were elevated in AKI rats. All of these abnormalities were prevented by AS
      IV. Furthermore, AS-IV downregulated the mRNA expression of NF- kappa B, TNF-
      alpha , MCP-1, and ICAM-1 in AKI rats. These results suggest that AS-IV might be
      developed as a novel therapeutic approach to prevent ischemic AKI through
      inhibition of NF- kappa B mediated inflammatory genes expression. 

PMID- 23853657
TI  - Effect of Piper betle and Brucea javanica on the Differential Expression of
      Hyphal Wall Protein (HWP1) in Non-Candida albicans Candida (NCAC) Species.
AB  - The study aimed to identify the HWP1 gene in non-Candida albicans Candida species
      and the differential expression of HWP1 following treatment with Piper betle and
      Brucea javanica aqueous extracts. All candidal suspensions were standardized to 1
      * 10(6) cells/mL. The suspension was incubated overnight at 37  degrees C (C.
      parapsilosis, 35 degrees C). Candidal cells were treated with each respective
      extract at 1, 3, and 6 mg/mL for 24 h. The total RNA was extracted and reverse
      transcription-polymerase chain reaction was carried out with a specific primer of
      HWP1. HWP1 mRNAs were only detected in C. albicans, C. parapsilosis, and C.
      tropicalis. Exposing the cells to the aqueous extracts has affected the
      expression of HWP1 transcripts. C. albicans, C. parapsilosis, and C. tropicalis
      have demonstrated different intensity of mRNA. Compared to P. betle, B. javanica
      demonstrated a higher suppression on the transcript levels of HWP1 in all
      samples. HWP1 was not detected in C. albicans following the treatment of B.
      javanica at 1 mg/mL. In contrast, C. parapsilosis and C. tropicalis were shown to
      have HWP1 regulation. However, the expression levels were reduced upon the
      addition of higher concentration of B. javanica extract. P. betle and B. javanica
      have potential to be developed as oral health product. 

PMID- 23853658
TI  - Observation of a long primo vessel in a lymph vessel from the inguinal node of a
      rabbit.
AB  - Though primo vessels are frequently found in the lymph near the abdominal aorta
      of rabbit by Alcian blue dye, the reproductions are still difficult to require
      considerable skills and technical know-how at dissected tissue of animal species.
      However, in the inguinal lymph node of a rabbit we found a long-type primo
      vascular system (LTP) dyed with Alcian blue, from an abdominal lymph vessel to an
      inguinal lymph node. The length of LTP was over an average length of 9.1 cm. The
      average diameters of the primo and the lymph vessels were about 23.9  MU m and
      242  MU m, respectively. The primo vessels were not floating but adhered to lymph
      vessels with fascial connective tissue. These primo vessels might be a functional
      integration in the lymph system. 

PMID- 23853659
TI  - Comparisons of prediction models of myofascial pain control after dry needling: a
      prospective study.
AB  - Background. This study purposed to validate the use of artificial neural network
      (ANN) models for predicting myofascial pain control after dry needling and to
      compare the predictive capability of ANNs with that of support vector machine
      (SVM) and multiple linear regression (MLR). Methods. Totally 400 patients who
      have received dry needling treatments completed the Brief Pain Inventory (BPI) at
      baseline and at 1 year postoperatively. Results. Compared to the MLR and SVM
      models, the ANN model generally had smaller mean square error (MSE) and mean
      absolute percentage error (MAPE) values in the training dataset and testing
      dataset. Most ANN models had MAPE values ranging from 3.4% to 4.6% and most had
      high prediction accuracy. The global sensitivity analysis also showed that
      pretreatment BPI score was the best parameter for predicting pain after dry
      needling. Conclusion. Compared with the MLR and SVM models, the ANN model in this
      study was more accurate in predicting patient-reported BPI scores and had higher
      overall performance indices. Further studies of this model may consider the
      effect of a more detailed database that includes complications and clinical
      examination findings as well as more detailed outcome data. 

PMID- 23853660
TI  - Effect of eucalyptus oil inhalation on pain and inflammatory responses after
      total knee replacement: a randomized clinical trial.
AB  - Eucalyptus oil has been reported effective in reducing pain, swelling, and
      inflammation. This study aimed to investigate the effects of eucalyptus oil
      inhalation on pain and inflammatory responses after total knee replacement (TKR)
      surgery. Participants were randomized 1 : 1 to intervention group (eucalyptus
      inhalation group) or control group (almond oil inhalation group). Patients
      inhaled eucalyptus or almond oil for 30 min of continuous passive motion (CPM) on
      3 consecutive days. Pain on a visual analog scale (VAS), blood pressure, heart
      rate, C-reactive protein (CRP) concentration, and white blood cell (WBC) count
      were measured before and after inhalation. Pain VAS on all three days (P < .001)
      and systolic (P < .05) and diastolic (P = .03) blood pressure on the second day
      were significantly lower in the group inhaling eucalyptus than that inhaling
      almond oil. Heart rate, CRP, and WBC, however, did not differ significantly in
      the two groups. In conclusion, inhalation of eucalyptus oil was effective in
      decreasing patient's pain and blood pressure following TKR, suggesting that
      eucalyptus oil inhalation may be a nursing intervention for the relief of pain
      after TKR. 

PMID- 23853661
TI  - Current understanding on antihepatocarcinoma effects of xiao chai hu tang and its
      constituents.
AB  - Xiao Chai Hu Tang (XCHT), a compound formula originally recorded in an ancient
      Chinese medical book Shanghanlun, has been used to treat chronic liver diseases
      for a long period of time in China. Although extensive studies have been
      demonstrated the efficacy of this formula to treat chronic hepatitis, hepatic
      fibrosis, and hepatocarcinoma, how it works against these diseases still awaits
      full understanding. Here, we firstly present an overview arranging from the
      entire formula to mechanism studies of single herb in XCHT and their active
      components, from a new perspective of "separation study," and we tried our best
      to both detailedly and systematically organize the antihepatocarcinoma effects of
      it, hoping that the review will facilitate the strive on elucidating how XCHT
      elicits its antihepatocarcinoma role. 

PMID- 23853662
TI  - Hepatoprotective Activity of Methanolic Extract of Bauhinia purpurea Leaves
      against Paracetamol-Induced Hepatic Damage in Rats.
AB  - In an attempt to further establish the pharmacological properties of Bauhinia
      purpurea (Fabaceae), hepatoprotective potential of methanol extract of B.
      purpurea leaves (MEBP) was investigated using the paracetamol- (PCM-) induced
      liver toxicity in rats. Five groups of rats (n = 6) were used and administered
      orally once daily with 10% DMSO (negative control), 200 mg/kg silymarin (positive
      control), or MEBP (50, 250, and 500 mg/kg) for 7 days, followed by the
      hepatotoxicity induction using paracetamol (PCM). The blood samples and livers
      were collected and subjected to biochemical and microscopical analysis. The
      extract was also subjected to antioxidant study using the 2, 2-diphenyl-1
      picrylhydrazyl (DPPH) radical scavenging assay with the total phenolic content
      (TPC) also determined. From the histological observation, lymphocyte infiltration
      and marked necrosis were observed in PCM-treated groups (negative control),
      whereas maintenance of the normal hepatic structural was observed in group
      pretreated with silymarin and MEBP. Hepatotoxic rats pretreated with silymarin or
      MEBP exhibited significant decrease (P < 0.05) in ALT and AST enzyme level.
      Moreover, the extract also exhibited antioxidant activity and contained high TPC.
      In conclusion, MEBP exerts potential hepatoprotective activity that could be
      partly attributed to its antioxidant activity and high phenolic content and thus
      warrants further investigation. 

PMID- 23853663
TI  - Chinese herbal medicine for the treatment of obesity-related hypertension.
AB  - Objectives. To assess the clinical evidence of Chinese herbal medicine (CHM) for
      obesity-related hypertension. Search Strategy. Electronic databases were searched
      until January, 2013. Inclusion Criteria. We included randomized clinical trials
      (RCTs) testing CHM against nondrug therapy and conventional western medicine, or
      combined with conventional western medicine against conventional western
      medicine. Data Extraction and Analyses. Study selection, data extraction, quality
      assessment, and data analyses were conducted according to Cochrane standards.
      Results. 11 trials were included. Methodological quality was evaluated as low. 1
      trial investigated the efficacy of CHM plus nondrug therapy versus nondrug
      therapy. Positive results in diastolic blood pressure (DBP) (WMD: -5.40 [-5.88, 
      4.92]; P < 0.00001) were found in combination group. 1 trial investigated the
      efficacy of CHM versus conventional western medicine. Positive results in
      systolic blood pressure (SBP) (WMD: -1.39 [-2.11, -0.67]; P = 0.0002) were found
      in CHM. 9 trials investigated the efficacy of CHM plus conventional western
      medicine versus conventional western medicine. Positive results in SBP (WMD: 
      6.71 [-11.08, -1.25]; P = 0.02) were found in combination group. The safety of
      CHM is unknown. Conclusions. No definite conclusion could be got due to poor
      methodological quality. Rigorously designed trials are warranted to confirm these
      results. 

PMID- 23853664
TI  - Differential Localization of Pain-Related and Pain-Unrelated Neural Responses for
      Acupuncture at BL60 Using BOLD fMRI.
AB  - The objective of this study was to differentiate between pain-related and pain
      unrelated neural responses of acupuncture at BL60 to investigate the specific
      effects of acupuncture. A total of 19 healthy volunteers were evaluated. fMRI was
      performed with sham or verum acupuncture stimulation at the left BL60 before and
      after local anesthesia. To investigate the relative BOLD signal effect for each
      session, a one-sample t-test was performed for individual contrast maps, and a
      paired t-test to investigate the differences between the pre- and post-anesthetic
      signal effects. Regarding verum acupuncture, areas that were more activated
      before local anesthesia included the superior, middle, and medial frontal gyri,
      inferior parietal lobule, superior temporal gyrus, thalamus, middle temporal
      gyrus, cingulate gyrus, culmen, and cerebellar tonsil. The postcentral gyrus was
      more deactivated before local anesthesia. After local anesthesia, the middle
      occipital gyrus, inferior temporal gyrus, postcentral gyrus, precuneus, superior
      parietal lobule, and declive were deactivated. Pre-anesthetic verum acupuncture
      at BL60 activated areas of vision and pain transmission. Post-anesthetic verum
      acupuncture deactivated brain areas of visual function, which is considered to be
      a pain-unrelated acupuncture response. It indicates that specific effects of
      acupoint BL60 are to control vision sense as used in the clinical setting. 

PMID- 23853665
TI  - Toward a theory of the primo vascular system: a hypothetical circulatory system
      at the subcellular level.
AB  - This paper suggests a theoretical framework for the primo vascular system (PVS),
      a hypothetical circulatory system, in which extracellular DNA microvesicles
      interact to form and break down cell structures. Since Bonghan Kim reported the
      existence of Bonghan ducts and the SNU research team reinvestigated and named it
      the PVS, there has been series of studies trying to examine its structure and
      functions. In this paper, we hypothesize that the PVS is the network system in
      which extracellular DNA microvesicles circulate and interact at the subcellular
      level, forming and breaking down cell structures. This idea integrates A.
      Bechamp's idea of microzymas and Bonghan Kim's idea of sanals. A proof of this
      idea may complement modern medical theory, perhaps providing an essential clue
      for an alternative solution dealing with modern healthcare problem. 

PMID- 23853667
TI  - Fast discriminative stochastic neighbor embedding analysis.
AB  - Feature is important for many applications in biomedical signal analysis and
      living system analysis. A fast discriminative stochastic neighbor embedding
      analysis (FDSNE) method for feature extraction is proposed in this paper by
      improving the existing DSNE method. The proposed algorithm adopts an alternative
      probability distribution model constructed based on its K-nearest neighbors from
      the interclass and intraclass samples. Furthermore, FDSNE is extended to
      nonlinear scenarios using the kernel trick and then kernel-based methods, that
      is, KFDSNE1 and KFDSNE2. FDSNE, KFDSNE1, and KFDSNE2 are evaluated in three
      aspects: visualization, recognition, and elapsed time. Experimental results on
      several datasets show that, compared with DSNE and MSNP, the proposed algorithm
      not only significantly enhances the computational efficiency but also obtains
      higher classification accuracy. 

PMID- 23853666
TI  - Clinical Applications of Omics Technologies on ZHENG Differentiation Research in
      Traditional Chinese Medicine.
AB  - Traditional Chinese medicine (TCM) ZHENG is the basic concept of TCM theory. The
      effectiveness of TCM treatment depends on the accuracy of ZHENG differentiation.
      ZHENG differentiation, using the "four diagnostic methods," has the drawbacks of
      subjectivity and variability. Following development of omics technologies, which
      study the functional activities of human body from a system-wide perspective, it
      has been more and more applied in study of objectivity differentiating TCM ZHENG
      and understanding its biological mechanisms. This paper reviewed the literatures
      of clinical TCM ZHENG differentiation researches, underlying omics technologies,
      and indicated the increased trends of related articles with four kinds of omics
      technologies, including genomics, transcriptomics, proteomics and metabolomics,
      and the correlations between ZHENG differentiation and findings in omics studies.
      Moreover, the paper summarized the typical omics application in common studied
      diseases and TCM ZHENGs and discussed the main problems and countermeasure of
      ZHENG differentiation researches. The work here may provide a reference for
      further research of TCM ZHENG differentiation using omics technologies. 

PMID- 23853668
TI  - Antibody Drug Conjugate bioinformatics: drug delivery through the letterbox.
AB  - Antibodies appear to be the first line of defence in the adaptive immune response
      of vertebrates and thereby are involved in a multitude of biochemical mechanisms,
      such as regulation of infection, autoimmunity, and cancer. It goes without saying
      that a full understanding of antibody function is required for the development of
      novel antibody-interacting drugs. These drugs are the Antibody Drug Conjugates
      (ADCs), which are a new type of targeted therapy, used for example for cancer.
      They consist of an antibody (or antibody fragment such as a single-chain variable
      fragment [scFv]) linked to a payload drug (often cytotoxic). Because of the
      targeting, the side effects should be lower and give a wider therapeutic window.
      Overall, the underlying principle of ADCs is to discern the delivery of a drug
      that is cytotoxic to a target that is cancerous, hoping to increase the
      antitumoural potency of the original drug by reducing adverse effects and side
      effects, such as toxicity of the cancer target. This is a pioneering field that
      employs state-of-the-art computational and molecular biology methods in the fight
      against cancer using ADCs. 

PMID- 23853669
TI  - Spatiotemporal dynamic simulation of acute perfusion/diffusion ischemic stroke
      lesions evolution: a pilot study derived from longitudinal MR patient data.
AB  - The spatiotemporal evolution of stroke lesions, from acute injury to final tissue
      damage, is complex. Diffusion-weighted (DWI) and perfusion-weighted (PWI) imaging
      is commonly used to detect early ischemic changes and attempts to distinguish
      between permanently damaged and salvageable tissues. To date, 2D and 3D measures
      of diffusion/perfusion regions at individual timepoints have been widely used but
      may underestimate the true lesion spatio-temporal dynamics. Currently there is no
      spatio-temporal 4D dynamic model that simulates the continuous evolution of
      ischemic stroke from MR images. We determined whether a 4D current-based
      diffeomorphic model, developed in the field of statistical modeling for measuring
      the variability of anatomical surfaces, could estimate patient-specific spatio
      temporal continuous evolution for MR PWI (measured as mean transit time, (MTT))
      and DWI lesions. In our representative pilot sample, the model fitted the data
      well. Our dynamic analysis of lesion evolution showed different patterns; for
      example, some DWI/PWI dynamic changes corresponded with DWI lesion expansion into
      PWI lesions, but other patterns were much more complex and diverse. There was
      wide variation in the time when the final tissue damage was reached after stroke
      for DWI and MTT. 

PMID- 23853670
TI  - Outside of the box: recent news about phospholipid translocation by P4 ATPases.
AB  - The P4 subfamily of P-type ATPases includes phospholipid transporters. Moving
      such bulky amphipathic substrate molecules across the membrane poses unique
      mechanistic problems. Recently, three papers from three different laboratories
      have offered insights into some of these problems. One effect of these
      experiments will be to ignite a healthy debate about the path through the enzyme
      taken by the substrate. A second effect is to suggest a counterintuitive model
      for the critical substrate-binding site. By putting concrete hypotheses into
      play, these papers finally provide a foundation for investigations of mechanism
      for these proteins. 

PMID- 23853673
TI  - Impending paradoxical embolism presenting as myocardial infarction.
AB  - : We present a spectrum of findings with transthoracic echocardiography, coronary
      angiography, and open surgical exploration in a 54-year-old man who presented
      with an acute ST segment elevation myocardial infarction and was diagnosed with
      impending paradoxical emboli. He underwent successful surgical removal of the
      thrombus. LEARNING OBJECTIVE: Impending paradoxical embolism, a biatrial
      thromboembolus in transit across a patent foramen ovale, is associated with a 20%
      mortality rate. Very rarely does it present as a ST segment elevation myocardial
      infarction. The optimal management (medical or surgical) for those who present
      with it remains a subject of debate, although surgery has been associated with
      less systemic embolization.

PMID- 23853672
TI  - The Role of PTEN in beta-Cell Growth.
AB  - This paper describes the biological functions of PTEN and the PTEN regulated
      signaling pathway in pancreatic beta-cells. PTEN has been shown to regulate the
      regeneration of beta-cells. We review the pathways that are controlled by PTEN
      signaling and their functions in beta-cell regeneration. In particular, we
      describe the unique effect of Pten deletion in beta-cells. Unlike its effect in
      other tissues, Pten deletion does not lead to tumor formation but does enhance
      beta-cell proliferation and function. In addition to the literature review, we
      also report new results exploring PTEN loss in adult beta-cells. We demonstrate
      that inducing PTEN loss in adult cells has the same regenerative effects
      previously found for prenatal deletion.

PMID- 23853671
TI  - Mechanism of the sex difference in endothelial dysfunction after stroke.
AB  - Stroke, the number four cause of death in the United States, is a greatly
      debilitating event resulting from insufficient blood supply to the brain
      (cerebral ischemia). Endothelial dysfunction, primarily characterized by dampened
      endothelial- dependent vasodilation, is a major contributor to the development
      and outcome of stroke. This review discusses the role of soluble epoxide
      hydrolase (sEH), an enzyme responsible for the degradation of vasoprotective
      eicosatrienoic acids (EETs), in the context of the cerebral vasculature and its
      contribution to the sexual dimorphic nature of stroke. 

PMID- 23853675
TI  - Open and closed loops: A computational approach to attention and consciousness.
AB  - Within recent years, researchers have proposed the independence of attention and
      consciousness on both empirical and conceptual grounds. However, the elusive
      nature of these constructs complicates progress in the investigation of their
      interaction. We present a framework within which we conceptualize attention and
      consciousness in computational terms. Here, the concepts are consi-dered as large
      scale, functionally and structurally different processes, embedded in a
      biologically inspired architecture, spanning the full arc from stimulus to
      response. Our architecture assumes a general independence of attention and
      consciousness, but supposes strong interactions. Furthermore, it addresses the
      developmental aspect, stressing that these functions have to gradually develop
      through learning. 

PMID- 23853676
TI  - Comparing the neural correlates of affective and cognitive theory of mind using
      fMRI: Involvement of the basal ganglia in affective theory of mind.
AB  - Theory of Mind (ToM) is the ability to infer other people's mental states like
      intentions or desires. ToM can be differentiated into affective (i.e.,
      recognizing the feelings of another person) and cognitive (i.e., inferring the
      mental state of the counterpart) subcomponents. Recently, subcortical structures
      such as the basal ganglia (BG) have also been ascribed to the multifaceted
      concept ToM and most BG disorders have been reported to elicit ToM deficits. In
      order to assess both the correlates of affective and cognitive ToM as well as
      involvement of the basal ganglia, 30 healthy participants underwent event-related
      fMRI scanning, neuropsychological testing, and filled in questionnaires
      concerning different aspects of ToM and empathy. Directly contrasting affective
      (aff) as well as cognitive (cog) ToM to the control (phy) condition, activation
      was found in classical ToM regions, namely parts of the temporal lobe including
      the superior temporal sulcus, the supplementary motor area, and parietal
      structures in the right hemisphere. The contrast aff > phy yielded additional
      activation in the orbitofrontal cortex on the right and the cingulate cortex, the
      precentral and inferior frontal gyrus and the cerebellum on the left. The right
      BG were recruited in this contrast as well. The direct contrast aff > cog showed
      activation in the temporoparietal junction and the cingulate cortex on the right
      as well as in the left supplementary motor area. The reverse contrast cog > aff
      however did not yield any significant clusters. In summary, affective and
      cognitive ToM partly share neural correlates but can also be differentiated
      anatomically. Furthermore, the BG are involved in affective ToM and thus their
      contribution is discussed as possibly providing a motor component of simulation
      processes, particularly in affective ToM. 

PMID- 23853677
TI  - Laparoscopic adrenalectomy by the lateral transperitoneal approach in patients
      with a history of previous abdominal surgery.
AB  - INTRODUCTION: Even the half of patients undergoing laparoscopic adrenalectomy has
      history of previous abdominal surgeries. However, it is still uncertain if this
      fact has an impact on the operation itself as well as the postoperative course.
      AIM: To analyze the effects of previous abdominal surgery on surgical outcomes in
      adrenal tumor patients subjected to laparoscopic adrenalectomy. MATERIAL AND
      METHODS: This study included 268 patients with adrenal gland tumors operated on
      by means of laparoscopic lateral transperitoneal adrenalectomy: 1) previously
      subjected to at least one abdominal surgery (group A, n = 101), or 2) with no
      history of previous abdominal operations (group B, n = 167). RESULTS: Groups A
      and B did not differ in terms of tumor size (p = 0.132), mean operation time (p =
      0.456), mean intraoperative blood loss (p = 0.754), or perioperative complication
      rate (p = 0.833). Dissection of intraperitoneal adhesions was considered
      difficult in 32 patients from group A (31.6%) and 8 subjects from group B (4.7%,
      p < 0.001). Conversion was required in three subjects from group A (2.9%) and 3
      patients from group B (1.8%, p = 0.529). CONCLUSIONS: Previous abdominal surgery
      does not constitute a contraindication to laparoscopic transperitoneal
      adrenalectomy.

PMID- 23853678
TI  - Translocation of nanoparticles through a polymer brush-modified nanochannel.
AB  - A basic understanding of the transport mechanisms of nanostructures in a polymer
      brush-modified nanochannel as well as the brush-nanostructure interactions at
      molecular level is important to design and fabricate emerging smart
      nano/microfluidic channels. In this work, we report coarse-grained molecular
      dynamics simulations of the translocation of nanoparticles through a cylindrical
      nanochannel coated with the polymer brush. The effects of the interparticle
      interaction and grafting density on the distribution and electrokinetic transport
      of nanoparticles are addressed in detail. Analysis of the distribution and
      velocity profiles of nanoparticles from the simulations indicate that the
      location of nanoparticles along the radial direction and their migration velocity
      are very sensitive to the change of interparticle interaction. We find
      complicated transport dynamics of nanoparticles under the influence of various
      grafting densities. The nanoparticles show markedly different translocation
      behavior upon increasing the grafting density, which depends on the counterion
      distribution, free room within the brush, nanoparticle-polymer friction, and
      brush configuration. Our results may serve as a useful starting point for the
      transport of nanostructures in polymer-modified channels and help to guide the
      design of novel smart nanofluidic channels for controlling the migration behavior
      of nanostructures. 

PMID- 23853679
TI  - Microfluidic separation of live and dead yeast cells using reservoir-based
      dielectrophoresis.
AB  - Separating live and dead cells is critical to the diagnosis of early stage
      diseases and to the efficacy test of drug screening, etc. This work demonstrates
      a novel microfluidic approach to dielectrophoretic separation of yeast cells by
      viability. It exploits the cell dielectrophoresis that is induced by the inherent
      electric field gradient at the reservoir-microchannel junction to selectively
      trap dead yeast cells and continuously separate them from live ones right inside
      the reservoir. This approach is therefore termed reservoir-based
      dielectrophoresis (rDEP). It has unique advantages as compared to existing
      dielectrophoretic approaches such as the occupation of zero channel space and the
      elimination of any mechanical or electrical parts inside microchannels. Such an
      rDEP cell sorter can be readily integrated with other components into lab-on-a
      chip devices for applications to biomedical diagnostics and therapeutics. 

PMID- 23853680
TI  - Microfluidic impedance spectroscopy as a tool for quantitative biology and
      biotechnology.
AB  - A microfluidic device that is able to perform dielectric spectroscopy is
      developed. The device consists of a measurement chamber that is 250 MUm thick and
      750 MUm in radius. Around 1000 cells fit inside the chamber assuming average
      quantities for cell radius and volume fraction. This number is about 1000 folds
      lower than the capacity of conventional fixtures. A T-cell leukemia cell line
      Jurkat is tested using the microfluidic device. Measurements of deionized water
      and salt solutions are utilized to determine parasitic effects and geometric
      capacitance of the device. Physical models, including Maxwell-Wagner mixture and
      double shell models, are used to derive quantities for sub-cellular units.
      Clausius-Mossotti factor of Jurkat cells is extracted from the impedance
      spectrum. Effects of cellular heterogeneity are discussed and parameterized.
      Jurkat cells are also tested with a time domain reflectometry system for
      verification of the microfluidic device. Results indicate good agreement of
      values obtained with both techniques. The device can be used as a unique cell
      diagnostic tool to yield information on sub-cellular units. 

PMID- 23853689
TI  - Retraction: Stereochemical insignificance discovered in Acinetobacter baumannii
      quorum sensing.

PMID- 23853691
TI  - Retraction: MiR-145 regulates epithelial to mesenchymal transition of breast
      cancer cells by targeting Oct4.

PMID- 23853695
TI  - Dams and disease triggers on the lower Mekong river.

PMID- 23853697
TI  - Humoral autoimmune response heterogeneity in the spectrum of primary biliary
      cirrhosis.
AB  - OBJECTIVE: To compare autoantibody features in patients with primary biliary
      cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but
      no clinical or biochemical evidence of disease. METHODS: A total of 212 AMA
      positive serum samples were classified into four groups: PBC (definite PBC, n =
      93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically
      normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples
      were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and
      ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100,
      and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG
      was determined by 8 M urea-modified ELISA. RESULTS: High-titer IIF-AMA was more
      frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and
      19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC
      and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013,
      respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36
      4.29) and PBC/AID samples (3.89; 3.15-4.63) than in BN (2.43; 1.92-2.94) and
      BN/AID samples (2.52; 1.54-3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in
      PBC (mean 64.5 %; 95 % CI 57.5-71.5 %) and PBC/AID samples (66.1 %; 54.4-77.8 %)
      than in BN samples (39.2 %; 30.9-37.5 %) (p < 0.001). PBC and PBC/AID recognized
      more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere)
      than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were
      independently associated with established PBC: high-avidity anti-PDC-E2 (OR
      4.121; 95 % CI 2.118-8.019); high-titer IIF-AMA (OR 4.890; 2.319-10.314);
      antibodies to three or more antigenic cell domains (OR 9.414; 1.924-46.060).
      CONCLUSION: The autoantibody profile was quantitatively and qualitatively more
      robust in definite PBC as compared with AMA-positive biochemically normal
      individuals.

PMID- 23853696
TI  - Evaluation of an electricity-free, culture-based approach for detecting typhoidal
      Salmonella bacteremia during enteric fever in a high burden, resource-limited
      setting.
AB  - BACKGROUND: In many rural areas at risk for enteric fever, there are few data on
      Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi)
      incidence, due to limited laboratory capacity for microbiologic culture. Here, we
      describe an approach that permits recovery of the causative agents of enteric
      fever in such settings. This approach involves the use of an electricity-free
      incubator based upon use of phase-change materials. We compared this against
      conventional blood culture for detection of typhoidal Salmonella.
      METHODOLOGY/PRINCIPAL FINDINGS: Three hundred and four patients with
      undifferentiated fever attending the outpatient and emergency departments of a
      public hospital in the Kathmandu Valley of Nepal were recruited. Conventional
      blood culture was compared against an electricity-free culture approach. Blood
      from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at
      least one of the two methods. Sixty-five (21.4%) patients tested blood culture
      positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65
      individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by
      the conventional blood culture and 60 (92.3%) were identified by the experimental
      method. Median time-to-positivity was 2 days for both procedures. The
      experimental approach was falsely positive due to probable skin contaminants in 2
      of 239 individuals (0.8%). The percentages of positive and negative agreement for
      diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%
      98.1%), respectively. After initial incubation, Salmonella isolates could be
      readily recovered from blood culture bottles maintained at room temperature for
      six months. CONCLUSIONS/SIGNIFICANCE: A simple culture approach based upon a
      phase-change incubator can be used to isolate agents of enteric fever. This
      approach could be used as a surveillance tool to assess incidence and drug
      resistance of the etiologic agents of enteric fever in settings without reliable
      local access to electricity or local diagnostic microbiology laboratories.

PMID- 23853698
TI  - IL28B polymorphisms predict the virological response to standard therapy in
      patients with chronic hepatitis C virus genotype 4 infection.
AB  - BACKGROUND: Genome-wide association studies have recently revealed that several
      single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can
      predict the sustained virological response (SVR) to pegylated interferon
      alpha2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However,
      data for patients infected with HCV genotype 4 (HCV-G4) are limited. AIM: We
      analyzed the association of IL28B SNPs (hematological, biochemical, virological,
      and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients.
      PATIENTS AND METHODS: One hundred twenty-nine treatment-naive HCV-G4 patients
      undergoing treatment were recruited from three tertiary care centers in Saudi
      Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and
      rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR
      was statistically correlated with various clinical, histopathological,
      virological, and genetic parameters. RESULTS: SVR was significantly associated
      with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004),
      respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039)
      showed significant differences in the SVR and No SVR groups. On multivariate
      analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6-6.2, p = 0.006) and
      albumin levels (OR, 1.2; 95 % CI 1.1-1.4, p = 0.001) independently predicted SVR.
      CONCLUSIONS: IL28B polymorphism (CC allele of rs12979860) predicts the sustained
      response to antiviral therapy in HCV-G4.

PMID- 23853699
TI  - Returns to Local-Area Healthcare Spending: Evidence from Health Shocks to
      Patients Far From Home.
AB  - Healthcare spending varies widely across markets, and previous empirical studies
      find little evidence that higher spending translates into better health outcomes.
      The main innovation in this paper exploits this cross-sectional variation in
      hospital spending in a new way by considering patients who are exposed to
      healthcare systems not designed for them: patients far from home when a health
      emergency strikes. Visitors to Florida who become ill in high-spending areas have
      significantly lower mortality rates compared to visitors in lower-spending areas.
      The results are robust within groups of similar visitors and within groups of
      destinations that appear to be close demand substitutes-areas that likely attract
      similar visitors.

PMID- 23853700
TI  - Bayesian inference on risk differences: an application to multivariate meta
      analysis of adverse events in clinical trials.
AB  - Multivariate meta-analysis is useful in combining evidence from independent
      studies which involve several comparisons among groups based on a single outcome.
      For binary outcomes, the commonly used statistical models for multivariate meta
      analysis are multivariate generalized linear mixed effects models which assume
      risks, after some transformation, follow a multivariate normal distribution with
      possible correlations. In this article, we consider an alternative model for
      multivariate meta-analysis where the risks are modeled by the multivariate beta
      distribution proposed by Sarmanov (1966). This model have several attractive
      features compared to the conventional multivariate generalized linear mixed
      effects models, including simplicity of likelihood function, no need to specify a
      link function, and has a closed-form expression of distribution functions for
      study-specific risk differences. We investigate the finite sample performance of
      this model by simulation studies and illustrate its use with an application to
      multivariate meta-analysis of adverse events of tricyclic antidepressants
      treatment in clinical trials.

PMID- 23853701
TI  - Multilevel analysis of bacterial counts from chronic periodontitis after root
      planing/scaling, surgery, and systemic and local antibiotics: 2-year results.
AB  - AIM: To follow changes (over 2 years) in subgingival bacterial counts of five
      microbial complexes including health-related Actinomyces spp. in deeper pockets
      (>=5 mm) after periodontal treatments. METHODS: EIGHT DIFFERENT TREATMENTS WERE
      STUDIED: (1) scaling+root planing (SRP); (2) periodontal surgery (SURG)+systemic
      amoxicillin (AMOX)+systemic metronidazole (MET); (3) SURG+locally delivered
      tetracycline (TET); (4) SURG; (5) AMOX+MET+TET; (6) AMOX+MET; (7) TET; and (8)
      SURG+AMOX+MET+TET. Antibiotics were given immediately following SRP. Subgingival
      plaque was collected mesiobuccally from each tooth, except third molars, from 176
      subjects, completing the study, at baseline, 3, 6, 12, 18, and 24 months post
      treatment and analysed for 40 different bacteria using checkerboard
      hybridization. A negative binomial (NB) generalized estimating equation (NB GEE)
      model was used to analyze count data and a logistic GEE was used for proportions.
      RESULTS: We observed short-term beneficial changes in the composition of the red
      complex of up to 3 months by treating subjects with AMOX+MET+TET. Similar short
      term improvements with the same treatment were observed for Tannerella forsythia
      and Treponema denticola of the red complex. SURG had also short-term beneficial
      effect on Porphyromonas gingivalis. No periodontal treatments applied to severely
      affected sites promoted the growth of Actinomyces. Smoking elevated counts of
      both the red and orange complex while bleeding on probing (BOP) and gingival
      redness were also predictors of more red complex counts. Comparatively similar
      findings were obtained by analyzing counts and by analyzing proportions.
      CONCLUSIONS: Although short-term reductions in the counts of the red complex were
      observed in sites that were treated with AMOX+MET+TET, long-term significant
      effects were not observed with any of the eight treatments. Poor oral hygiene in
      patients with severe chronic periodontitis diminished the beneficial effects of
      treatment.

PMID- 23853702
TI  - Basic aspects for improving the energy conversion efficiency of hetero-junction
      organic photovoltaic cells.
AB  - Hetero-junction organic photovoltaic (OPV) cells consisting of donor (D) and
      acceptor (A) layers have been regarded as next-generation PV cells, because of
      their fascinating advantages, such as lightweight, low fabrication cost, resource
      free, and flexibility, when compared to those of conventional PV cells based on
      silicon and semiconductor compounds. However, the power conversion efficiency
      (eta) of the OPV cells has been still around 8%, though more than 10% efficiency
      has been required for their practical use. To fully optimize these OPV cells, it
      is necessary that the low mobility of carriers/excitons in the OPV cells and the
      open circuit voltage (V OC), of which origin has not been understood well, should
      be improved. In this review, we address an improvement of the mobility of
      carriers/excitons by controlling the crystal structure of a donor layer and
      address how to increase the V OC for zinc octaethylporphyrin [Zn(OEP)]/C60 hetero
      junction OPV cells [ITO/Zn(OEP)/C60/Al]. It was found that crystallization of
      Zn(OEP) films increases the number of inter-molecular charge transfer (IMCT)
      excitons and enlarges the mobility of carriers and IMCT excitons, thus
      significantly improving the external quantum efficiency (EQE) under illumination
      of the photoabsorption band due to the IMCT excitons. Conversely, charge
      accumulation of photo-generated carriers in the vicinity of the donor/acceptor
      (D/A) interface was found to play a key role in determining the V OC for the OPV
      cells. 

PMID- 23853703
TI  - An integrative, translational approach to understanding rare and orphan
      genetically based diseases.
AB  - PhenomeNet is an approach for integrating phenotypes across species and
      identifying candidate genes for genetic diseases based on the similarity between
      a disease and animal model phenotypes. In contrast to 'guilt-by-association'
      approaches, PhenomeNet relies exclusively on the comparison of phenotypes to
      suggest candidate genes, and can, therefore, be applied to study the molecular
      basis of rare and orphan diseases for which the molecular basis is unknown. In
      addition to disease phenotypes from the Online Mendelian Inheritance in Man
      (OMIM) database, we have now integrated the clinical signs from Orphanet into
      PhenomeNet. We demonstrate that our approach can efficiently identify known
      candidate genes for genetic diseases in Orphanet and OMIM. Furthermore, we find
      evidence that mutations in the HIP1 gene might cause Bassoe syndrome, a rare
      disorder with unknown genetic aetiology. Our results demonstrate that integration
      and computational analysis of human disease and animal model phenotypes using
      PhenomeNet has the potential to reveal novel insights into the pathobiology
      underlying genetic diseases. 

PMID- 23853704
TI  - A generalized mathematical framework for estimating the residue function for
      arbitrary vascular networks.
AB  - The microvasculature plays a vital part in the cardiovascular system. Any
      impairment to its function can lead to significant pathophysiological effects,
      particularly in organs such as the brain where there is a very tight coupling
      between structure and function. However, it is extremely difficult to quantify
      the health of the microvasculature in vivo, other than by assessing perfusion,
      using techniques such as arterial spin labelling. Recent work has suggested that
      the flow distribution within a voxel could also be a valuable measure. This can
      also be measured clinically, but as yet has not been related to the properties of
      the microvasculature due to the difficulties in modelling and characterizing
      these strongly inter-connected networks. In this paper, we present a new
      technique for characterizing an existing physiologically accurate model of the
      cerebral microvasculature in terms of its residue function. A new analytical
      mathematical framework for calculation of the residue function, based on the mass
      transport equation, of any arbitrary network is presented together with results
      from simulations. We then present a method for characterizing this function,
      which can be directly related to clinical data, and show how the resulting
      parameters are affected under conditions of both reduced perfusion and reduced
      network density. It is found that the residue function parameters are affected in
      different ways by these two effects, opening up the possibility of using such
      parameters, when acquired from clinical data, to infer information about both the
      network properties and the perfusion distribution. These results open up the
      possibility of obtaining valuable clinical information about the health of the
      microvasculature in vivo, providing additional tools to clinicians working in
      cerebrovascular diseases, such as stroke and dementia. 

PMID- 23853705
TI  - Applications of analysis of dynamic adaptations in parameter trajectories.
AB  - Metabolic profiling in combination with pathway-based analyses and computational
      modelling are becoming increasingly important in clinical and preclinical
      research. Modelling multi-factorial, progressive diseases requires the
      integration of molecular data at the metabolome, proteome and transcriptome
      levels. Also the dynamic interaction of organs and tissues needs to be
      considered. The processes involved cover time scales that are several orders of
      magnitude different. We report applications of a computational approach to bridge
      the scales and different levels of biological detail. Analysis of dynamic
      adaptations in parameter trajectories (ADAPTs) aims to investigate phenotype
      transitions during disease development and after a therapeutic intervention.
      ADAPT is based on a time-dependent evolution of model parameters to describe the
      dynamics of metabolic adaptations. The progression of metabolic adaptations is
      predicted by identifying necessary dynamic changes in the model parameters to
      describe the transition between experimental data obtained during different
      stages. To get a better understanding of the concept, the ADAPT approach is
      illustrated in a theoretical study. Its application in research on progressive
      changes in lipoprotein metabolism is also discussed. 

PMID- 23853706
TI  - Risk factor-dependent dynamics of atopic dermatitis: modelling multi-scale
      regulation of epithelium homeostasis.
AB  - Epithelial tissue provides the body with its first layer of protection against
      harmful environmental stimuli by enacting the regulatory interplay between a
      physical barrier preventing the influx of external stimuli and an inflammatory
      response to the infiltrating stimuli. Importantly, this interdependent regulation
      occurs on different time scales: the tissue-level barrier permeability is
      regulated over the course of hours, whereas the cellular-level enzymatic
      reactions leading to inflammation take place within minutes. This multi-scale
      regulation is key to the epithelium's function and its dysfunction leads to
      various diseases. This paper presents a mathematical model of regulatory
      mechanisms in the epidermal epithelium that includes processes on two different
      time scales at the cellular and tissue levels. We use this model to investigate
      the essential regulatory interactions between epidermal barrier integrity and
      skin inflammation and how their dysfunction leads to atopic dermatitis (AD). Our
      model exhibits a structure of dual (positive and negative) control at both
      cellular and tissue levels. We also determined how the variation induced by well
      known risk factors for AD can break the balance of the dual control. Our model
      analysis based on time-scale separation suggests that each risk factor leads to
      qualitatively different dynamic behaviours of different severity for AD, and that
      the coincidence of multiple risk factors dramatically increases the fragility of
      the epithelium's function. The proposed mathematical framework should also be
      applicable to other inflammatory diseases that have similar time-scale separation
      and control architectures. 

PMID- 23853707
TI  - Detecting adenosine triphosphate in the pericellular space.
AB  - Release of adenosine triphosphate (ATP) into the extracellular space occurs in
      response to a multiplicity of physiological and pathological stimuli in virtually
      all cells and tissues. A role for extracellular ATP has been identified in
      processes as different as neurotransmission, endocrine and exocrine secretion,
      smooth muscle contraction, bone metabolism, cell proliferation, immunity and
      inflammation. However, ATP measurement in the extracellular space has proved a
      daunting task until recently. To tackle this challenge, some years ago, we
      designed and engineered a novel luciferase probe targeted to and expressed on the
      outer aspect of the plasma membrane. This novel probe was constructed by
      appending to firefly luciferase the N-terminal leader sequence and the C-terminal
      glycophosphatidylinositol anchor of the folate receptor. This chimeric protein,
      named plasma membrane luciferase, is targeted and localized to the outer side of
      the plasma membrane. With this probe, we have generated stably transfected HEK293
      cell clones that act as an in vitro and in vivo sensor of the extracellular ATP
      concentration in several disease conditions, such as experimentally induced
      tumours and inflammation. 

PMID- 23853708
TI  - From seeing to believing: labelling strategies for in vivo cell-tracking
      experiments.
AB  - Intravital microscopy has become increasingly popular over the past few decades
      because it provides high-resolution and real-time information about complex
      biological processes. Technological advances that allow deeper penetration in
      live tissues, such as the development of confocal and two-photon microscopy,
      together with the generation of ever-new fluorophores that facilitate bright
      labelling of cells and tissue components have made imaging of vertebrate model
      organisms efficient and highly informative. Genetic manipulation leading to
      expression of fluorescent proteins is undoubtedly the labelling method of choice
      and has been used to visualize several cell types in vivo. This approach,
      however, can be technically challenging and time consuming. Over the years,
      several dyes have been developed to allow rapid, effective and bright ex vivo
      labelling of cells for subsequent transplantation and imaging. Here, we review
      and discuss the advantages and limitations of a number of strategies commonly
      used to label and track cells at high resolution in vivo in mouse and zebrafish,
      using fluorescence microscopy. While the quest for the perfect label is far from
      achieved, current reagents are valuable tools enabling the progress of biological
      discovery, so long as they are selected and used appropriately. 

PMID- 23853709
TI  - Nutrient restriction enhances the proliferative potential of cells lacking the
      tumor suppressor PTEN in mitotic tissues.
AB  - How single cells in a mitotic tissue progressively acquire hallmarks of cancer is
      poorly understood. We exploited mitotic recombination in developing Drosophila
      imaginal tissues to analyze the behavior of cells devoid of the tumor suppressor
      PTEN, a negative regulator of PI3K signaling, under varying nutritional
      conditions. Cells lacking PTEN strongly overproliferated specifically in nutrient
      restricted larvae. Although the PTEN mutant cells were sensitive to starvation,
      they successfully competed with neighboring cells by autonomous and non
      autonomous mechanisms distinct from cell competition. The overgrowth was strictly
      dependent on the activity of the downstream components Akt/PKB and TORC1, and a
      reduction in amino acid uptake by reducing the levels of the amino acid
      transporter Slimfast caused clones of PTEN mutant cells to collapse. Our findings
      demonstrate how limiting nutritional conditions impact on cells lacking the tumor
      suppressor PTEN to cause hyperplastic overgrowth.
      DOI:http://dx.doi.org/10.7554/eLife.00380.001. 

PMID- 23853710
TI  - Apical targeting of the formin Diaphanous in Drosophila tubular epithelia.
AB  - Apical secretion from epithelial tubes of the Drosophila embryo is mediated by
      apical F-actin cables generated by the formin-family protein Diaphanous (Dia).
      Apical localization and activity of Dia are at the core of restricting F-actin
      formation to the correct membrane domain. Here we identify the mechanisms that
      target Dia to the apical surface. PI(4,5)P2 levels at the apical membrane
      regulate Dia localization in both the MDCK cyst model and in Drosophila tubular
      epithelia. An N-terminal basic domain of Dia is crucial for apical localization,
      implying direct binding to PI(4,5)P2. Dia apical targeting also depends on
      binding to Rho1, which is critical for activation-induced conformational change,
      as well as physically anchoring Dia to the apical membrane. We demonstrate that
      binding to Rho1 facilitates interaction with PI(4,5)P2 at the plane of the
      membrane. Together these cues ensure efficient and distinct restriction of Dia to
      the apical membrane. DOI:http://dx.doi.org/10.7554/eLife.00666.001. 

PMID- 23853711
TI  - Phosphorylation-mediated PTEN conformational closure and deactivation revealed
      with protein semisynthesis.
AB  - The tumor suppressor PIP3 phosphatase PTEN is phosphorylated on four clustered
      Ser/Thr on its C-terminal tail (aa 380-385) and these phosphorylations are
      proposed to induce a reduction in PTEN's plasma membrane recruitment. How these
      phosphorylations affect the structure and enzymatic function of PTEN is poorly
      understood. To gain insight into the mechanistic basis of PTEN regulation by
      phosphorylation, we generated semisynthetic site-specifically tetra
      phosphorylated PTEN using expressed protein ligation. By employing a combination
      of biophysical and enzymatic approaches, we have found that purified tail
      phosphorylated PTEN relative to its unphosphorylated counterpart shows reduced
      catalytic activity and membrane affinity and undergoes conformational compaction
      likely involving an intramolecular interaction between its C-tail and the C2
      domain. Our results suggest that there is a competition between membrane
      phospholipids and PTEN phospho-tail for binding to the C2 domain. These findings
      reveal a key aspect of PTEN's regulation and suggest pharmacologic approaches for
      direct PTEN activation. DOI:http://dx.doi.org/10.7554/eLife.00691.001. 

PMID- 23853712
TI  - TRiC's tricks inhibit huntingtin aggregation.
AB  - In Huntington's disease, a mutated version of the huntingtin protein leads to
      cell death. Mutant huntingtin is known to aggregate, a process that can be
      inhibited by the eukaryotic chaperonin TRiC (TCP1-ring complex) in vitro and in
      vivo. A structural understanding of the genesis of aggregates and their
      modulation by cellular chaperones could facilitate the development of therapies
      but has been hindered by the heterogeneity of amyloid aggregates. Using cryo
      electron microscopy (cryoEM) and single particle cryo-electron tomography (SPT)
      we characterize the growth of fibrillar aggregates of mutant huntingtin exon 1
      containing an expanded polyglutamine tract with 51 residues (mhttQ51), and
      resolve 3-D structures of the chaperonin TRiC interacting with mhttQ51. We find
      that TRiC caps mhttQ51 fibril tips via the apical domains of its subunits, and
      also encapsulates smaller mhtt oligomers within its chamber. These two
      complementary mechanisms provide a structural description for TRiC's inhibition
      of mhttQ51 aggregation in vitro. DOI:http://dx.doi.org/10.7554/eLife.00710.001. 

PMID- 23853713
TI  - Hypothemycin, a fungal natural product, identifies therapeutic targets in
      Trypanosoma brucei [corrected].
AB  - Protein kinases are potentially attractive therapeutic targets for neglected
      parasitic diseases, including African trypanosomiasis caused by the protozoan,
      Trypanosoma brucei. How to prioritize T. brucei kinases and quantify their
      intracellular engagement by small-molecule inhibitors remain unsolved problems.
      Here, we combine chemoproteomics and RNA interference to interrogate trypanosome
      kinases bearing a Cys-Asp-Xaa-Gly motif (CDXG kinases). We discovered that
      hypothemycin, a fungal polyketide previously shown to covalently inactivate a
      subset of human CDXG kinases, kills T. brucei in culture and in infected mice.
      Quantitative chemoproteomic analysis with a hypothemycin-based probe revealed the
      relative sensitivity of endogenous CDXG kinases, including TbGSK3short and a
      previously uncharacterized kinase, TbCLK1. RNAi-mediated knockdown demonstrated
      that both kinases are essential, but only TbCLK1 is fully engaged by cytotoxic
      concentrations of hypothemycin in intact cells. Our study identifies TbCLK1 as a
      therapeutic target for African trypanosomiasis and establishes a new
      chemoproteomic tool for interrogating CDXG kinases in their native context.
      DOI:http://dx.doi.org/10.7554/eLife.00712.001. 

PMID- 23853714
TI  - Skill learning strengthens cortical representations of motor sequences.
AB  - Motor-skill learning can be accompanied by both increases and decreases in brain
      activity. Increases may indicate neural recruitment, while decreases may imply
      that a region became unimportant or developed a more efficient representation of
      the skill. These overlapping mechanisms make interpreting learning-related
      changes of spatially averaged activity difficult. Here we show that motor-skill
      acquisition is associated with the emergence of highly distinguishable activity
      patterns for trained movement sequences, in the absence of average activity
      increases. During functional magnetic resonance imaging, participants produced
      either four trained or four untrained finger sequences. Using multivariate
      pattern analysis, both untrained and trained sequences could be discriminated in
      primary and secondary motor areas. However, trained sequences were classified
      more reliably, especially in the supplementary motor area. Our results indicate
      skill learning leads to the development of specialized neuronal circuits, which
      allow the execution of fast and accurate sequential movements without average
      increases in brain activity. DOI:http://dx.doi.org/10.7554/eLife.00801.001. 

PMID- 23853715
TI  - Closing in on a new treatment for sleeping sickness.
AB  - A chemoproteomics approach has been employed to identify a kinase that could be
      used as a druggable target in efforts to develop new treatments for African
      sleeping sickness. 

PMID- 23853716
TI  - Autonomic involvement in subacute and chronic immune-mediated neuropathies.
AB  - Autonomic function can be impaired in many disorders in which sympathetic,
      parasympathetic, and enteric arms of the autonomic nervous system are affected.
      Signs and symptoms of autonomic involvement are related to impairment of
      cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and
      pupillomotor autonomic functions. Availability of noninvasive, sensitive, and
      reproducible tests can help to recognize these disorders and to better understand
      specific mechanisms of some, potentially treatable, immune-mediated autonomic
      neuropathies. This paper describes autonomic involvement in immune-mediated
      neuropathies with a subacute or chronic course. 

PMID- 23853717
TI  - Obesity and preference-weighted quality of life of ethnically diverse middle
      school children: the HEALTHY study.
AB  - To date, studies examining the relation between body mass index percentile (BMI%)
      categories and health-related quality of life (QOL) measurements have not
      reported preference-weighted scores among ethnically diverse children. We report
      the associations between BMI% categories and preference-weighted scores among a
      large cohort of ethnically diverse sixth grade children who participated in the
      HEALTHY school-based type 2 diabetes risk factor prevention study. Health Utility
      Index 2 (HUI2) and Health Utility Index 3 (HUI3) and the feeling thermometer (FT)
      were the preference-weighted QOL instruments used to measure student's preference
      scores. Of 6358 consented students, 4979 (78.3%) had complete QOL, height,
      weight, and covariate data. Mean (SD) preference scores were 0.846 (0.160), 0.796
      (0.237), and 0.806 (0.161) for the HUI2, HUI3, and FT, respectively. After
      adjusting for age, sex, blood glucose and insulin, Tanner stage, race/ethnicity,
      family history of diabetes, and educational attainment, children with severe
      obesity (>99%) had significantly lower preference scores compared to normal
      weight on all three instruments (HUI2 P = 0.013; HUI3 P = 0.025; and FT P <
      0.001). Obese and severe obese categories were significantly associated with
      lower HUI2 functional ratings in the mobility domain and with lower HUI3
      functional ratings in the speech domain. 

PMID- 23853718
TI  - Prevalence and Impact of Anxiety and Depression on Type 2 Diabetes in Tunisian
      Patients over Sixty Years Old.
AB  - Objectives. To estimate the prevalence of anxiety and depression using the
      Hospital Anxiety and Depression Scale (HADS) in a population aged over sixty
      years with type 2 diabetes and to study the impact of anxiety and depression on
      glycemic balance and disease outcome. Results. The prevalence of anxiety and
      depression in the 62 subjects included in the study was, respectively, 40.3% and
      22.6%. We found a relationship between these disorders and complicated diabetes.
      The subjects having an imperfectly balanced diabetes had a higher average anxiety
      score than those having a good glycemic control (9.1 +/- 4.2 versus 6.5 +/- 3.1;
      P = 0.017). No relationship was found between diabetes balance and depression.
      Conclusion. Association between anxiety and depressive disorders and diabetes is
      frequent and worsens patients' outcome, in terms of diabetes imbalance as well as
      in terms of diabetic complications. Our study shows that there is need for
      physicians to detect, confirm, and treat anxiety and depressive disorders in
      elderly diabetic patients. 

PMID- 23853719
TI  - The role of attention to emotion in recovery from major depressive disorder.
AB  - Major Depressive Disorder (MDD) is characterized by several emotional
      disturbances. One possible but not well-examined disturbance is in attention to
      emotion, an important facet of emotional awareness. We examined whether attention
      to emotion predicted recovery from MDD. Fifty-three adults with current MDD
      completed a week of experience sampling (Time 1). At each prompt, participants
      reported attention to emotion, negative affect (NA), and positive affect (PA).
      Approximately one year later (Time 2), the depressive status of 27 participants
      was reassessed. Participants who had recovered from MDD (n = 8) indicated paying
      less attention to their emotions at Time 1 than did participants who had not
      fully recovered (n = 19). Attention to emotion was better predictor of recovery
      than was severity of MDD, NA, or PA at Time 1. Levels of attention to emotion at
      Time 1 in participants who recovered from MDD did not differ significantly from
      the levels reported by 53 never-depressed individuals who had participated in the
      experience sampling. Findings indicate that high levels of an otherwise adaptive
      emotional facet can adversely affect the course of MDD. 

PMID- 23853720
TI  - Why are seizures rare in rapid eye movement sleep? Review of the frequency of
      seizures in different sleep stages.
AB  - Since the formal characterization of sleep stages, there have been reports that
      seizures may preferentially occur in certain phases of sleep. Through ascending
      cholinergic connections from the brainstem, rapid eye movement (REM) sleep is
      physiologically characterized by low voltage fast activity on the
      electroencephalogram, REMs, and muscle atonia. Multiple independent studies
      confirm that, in REM sleep, there is a strikingly low proportion of seizures (~1%
      or less). We review a total of 42 distinct conventional and intracranial studies
      in the literature which comprised a net of 1458 patients. Indexed to duration, we
      found that REM sleep was the most protective stage of sleep against focal
      seizures, generalized seizures, focal interictal discharges, and two particular
      epilepsy syndromes. REM sleep had an additional protective effect compared to
      wakefulness with an average 7.83 times fewer focal seizures, 3.25 times fewer
      generalized seizures, and 1.11 times fewer focal interictal discharges. In
      further studies REM sleep has also demonstrated utility in localizing
      epileptogenic foci with potential translation into postsurgical seizure freedom.
      Based on emerging connectivity data in sleep, we hypothesize that the influence
      of REM sleep on seizures is due to a desynchronized EEG pattern which reflects
      important connectivity differences unique to this sleep stage. 

PMID- 23853721
TI  - An fc gamma receptor-mediated upregulation of the production of interleukin 10 by
      intravenous immunoglobulin in bone-marrow-derived mouse dendritic cells
      stimulated with lipopolysaccharide in vitro.
AB  - Intravenous immunoglobulin (IVIG), a highly purified immunoglobulin fraction
      prepared from pooled plasma of several thousand donors, increased anti
      inflammatory cytokine IL-10 production, while decreased proinflammatory cytokine
      IL-12p70 production in bone-marrow-derived mouse dendritic cells (BMDCs)
      stimulated with lipopolysaccharide (LPS). The changes of cytokine production were
      confirmed with the transcription levels of these cytokines. To study the
      mechanisms of this bidirectional effect, we investigated changes of intracellular
      molecules in the LPS-induced signaling pathway and observed that IVIG upregulated
      ERK1/2 phosphorylation while downregulated p38 MAPK phosphorylation. Using
      chemical inhibitors specific to protein kinases involved in activation of Fc
      gamma receptors (FcgammaRs), which mediate IgG signals, we found that
      hyperphosphorylation of ERK1/2 and Syk phosphorylation occurred after stimulation
      of BMDC with LPS and IVIG, and the increasing effect on IL-10 production was
      abolished by these inhibitors. Furthermore, an antibody specific to FcgammaRI,
      one of FcgammaRs involved in immune activation, inhibited IVIG-induced increases
      in IL-10 production, but not IL-12p70 decreases, whereas the anti-IL-10 antibody
      restored the decrease in IL-12p70 induced by IVIG. These findings suggest that
      IVIG induced the upregulation of IL-10 production through FcgammaRI activation,
      and IL-10 was indispensable to the suppressing effect of IVIG on the production
      of IL-12p70 in LPS-stimulated BMDC. 

PMID- 23853722
TI  - Parkinson's disease and forced exercise: a preliminary study.
AB  - Objective. The concept of forced exercise has drawn attention for the treatment
      of Parkinson's disease symptoms with anecdotal reports of success. This study
      sought to ascertain any significant effect of forced exercise using a motorized
      stationary bicycle when compared to controls on Parkinson's disease symptoms in a
      blinded, randomized, and controlled setting. Setting. Parkinson's disease
      outpatient clinic, Veterans Administration Medical Center. Method. We assessed 23
      patients (13 experimental and 10 controls) on a number of standard Parkinson's
      measures at baseline, after participation in eight weeks of twice weekly forced
      exercise or eight weeks of conventional clinic care, and then after a three-month
      period had elapsed. Dependent measures were UPDRS-III, Berg Balance Scale, finger
      taping test, and the PDQ-39. Results. Results did not demonstrate any main effect
      differences between the exercise and control groups on any measure at any point
      in time. A within subjects effect was demonstrated for the forced exercise group
      on overall UPDRS-III scores at the three-month end point. No other within group
      effects were noted. Results suggest that early enthusiasm for forced exercise may
      need tempering. Limitations of the study are discussed as well as numerous
      logistical challenges to this type of study. 

PMID- 23853723
TI  - Demonstration of hepatitis C virus RNA with in situ hybridization employing a
      locked nucleic Acid probe in humanized liver of infected chimeric mice and in
      needle-biopsied human liver.
AB  - Background. In situ hybridization (ISH) with high sensitivity has been requested
      to demonstrate hepatitis C virus (HCV) RNA in formalin-fixed, paraffin-embedded
      (FFPE) sections of the liver. Methods. ISH employing a locked-nucleic-acid- (LNA
      )modified oligonucleotide probe and biotin-free catalyzed signal amplification
      system (CSAII) was applied to HCV-RNA detection in the liver tissue. Nested
      reverse-transcription polymerase chain reaction (RT-PCR) was performed for HCV
      genotyping using total RNA extracted from FFPE sections. The target tissues
      included FFPE tissue sections of humanized livers in HCV-infected chimeric mice
      (HCV genotypes 1a, 1b, and 2a and noninfected) and of needle-biopsied livers from
      HCV-infected patients. Results. HCV-RNA was demonstrated with the ISH technique
      in HCV-infected liver tissues from both chimeric mice and 9 (82%) of 11 patients
      with HCV infection. The HCV signals were sensitive to RNase. Nested RT-PCR
      confirmed the genotype in 8 (73%) of 11 livers (type 1b: 6 lesions and type 2a: 2
      lesions). HCV-RNA was not identified in chronic hepatitis B lesions, fatty liver,
      autoimmune hepatitis, and hepatocellular carcinoma. Conclusion. ISH using the LNA
      modified oligonucleotide probe and CSAII was applicable to detecting HCV-RNA in
      routinely prepared FFPE liver specimens. 

PMID- 23853724
TI  - Expression level of IL-6 secreted by bone marrow stromal cells in mice with
      aplastic anemia.
AB  - Parasecretion of the hematopoietic cytokines is considered as one of the
      mechanisms account for bone marrow hematopoiesis disorder. In this study, the
      level of IL-6 secreted by bone marrow stromal cells from a mouse model of
      aplastic anemia was analyzed. The aplastic anemia mouse model was established
      with cyclophosphamide in combination with chloramphenicol and (60)Co gamma
      radiation. The impairment of bone marrow hematopoiesis induced by irradiation and
      chemotherapeutic drugs was subsequently characterized by peripheral blood cell
      count, pathomorphological changes, and apoptosis rate. Furthermore, the in vitro
      proliferation of bone marrow stromal cells (BMSC) and the IL-6 secretion levels
      of BMSC were analyzed. In our model of aplastic anemia, the number of peripheral
      blood cells and bone marrow cells (BMC) were notably decreased, and the apoptosis
      rate of BMC increased. Furthermore, the proliferation of BMSC was obviously
      impeded while the IL-6 secretion levels of BMSC significantly increased. The
      findings of our study suggested that the IL-6 secretion level may be enhanced to
      some extent by the induction of aplastic anemia caused by irradiation and
      chemotherapeutic drugs and that the abnormal level of IL-6 might probably
      interfere with the stability of the bone marrow hematopoietic microenvironment. 

PMID- 23853725
TI  - Mullerian inhibiting substance suppresses proliferation and induces apoptosis and
      autophagy in endometriosis cells in vitro.
AB  - Objective. To determine the effects of Mullerian inhibiting substance (MIS)
      treatment on endometriosis cells through study of apoptosis and autophagy.
      Design. Experimental in vitro study. Setting. University research laboratory.
      Cell Line. CRL-7566 endometriosis cell line. This line was established from a
      benign ovarian cyst taken from a patient with endometriosis. Interventions. In
      vitro treatment with MIS. Main Outcome Measures. The main outcome measures were
      cellular viability, proliferation, cell-cycle arrest, and induction of apoptosis
      and autophagy in endometriotic cells. Results. MIS treatment inhibited
      proliferation of endometriosis cells and induced apoptosis, as indicated by
      Annexin V staining, and induced caspase-9 cleavage and cell-cycle arrest, as
      evidenced by increased expression of p27 CDK-inhibitor. MIS treatment also
      induced autophagy in endometriosis cells as demonstrated by a significant
      increase in LC3-II induction, a hallmark of autophagy. Conclusions. MIS inhibits
      cell growth and induces autophagy, as well as apoptosis, in ectopic endometrial
      cell lines. Our results suggest that MIS may have a potential as a novel approach
      for medical treatment of endometriosis. Further studies may be needed to test the
      efficacy of MIS treatment in animal models and to develop MIS treatment
      specifically targeted to the endometriosis. 

PMID- 23853726
TI  - Vitamin D Receptor Gene BsmI Polymorphism in Polish Patients with Systemic Lupus
      Erythematosus.
AB  - The hormonally active form of vitamin D3, 1,25(OH)2D3 (calcitriol), exerts
      actions through VDR receptor, which acts as a transcriptional factor. Calcitriol
      is an immunomodulator that affects various immune cells, and several studies link
      it to many autoimmune diseases. BsmI polymorphism affects the level of VDR gene
      transcription, transcript stability, and posttranscriptional modifications. It
      seems to be related to the systemic lupus erythematosus (SLE). Our study examined
      the characteristics of VDR gene BsmI polymorphism in Polish SLE patients and
      their relationship with clinical manifestations of the disease. We genotyped 62
      patients with SLE and 100 healthy controls using the real-time PCR. There were no
      differences observed in the frequency of BsmI genotypes in SLE patients and in
      the control group. There was no significant correlation between BsmI genotypes
      and clinical symptoms of SLE, but the AA genotype correlates with higher levels
      of antinuclear antibodies (ANA) in this group (r = 0.438; P = 0.002). A larger
      study examining BsmI and other VDR gene polymorphisms is needed. It may allow
      explaining differences in the clinical picture of the disease and choosing a
      personalized therapy. 

PMID- 23853727
TI  - Orthodontic Wire Ingestion during Treatment: Reporting a Case and Review the
      Management of Foreign Body Ingestion or Aspiration (Emergencies).
AB  - Today orthodontic treatment is in growing demand and is not limited to a specific
      age or social group. The nature of orthodontic treatment is such that the
      orthodontic wires and appliances, which are used to apply force and move the
      teeth, are exposed to the oral cavity. Shaping and replacing these wires in oral
      cavity are the major assignments of orthodontist on appointments. Therefore, we
      can say that orthodontic treatment requires working with dangerous tools in a
      sensitive place like oral cavity which is the entrance of respiratory and
      digestive systems. In this paper, a case of ingesting a broken orthodontic wire
      during eating is reported, and also necessary remedial measures at the time of
      encountering foreign body ingestion or aspiration are provided. 

PMID- 23853728
TI  - Neuroleptic malignant syndrome in a patient with tongue cancer: a report of a
      rare case.
AB  - Background. Neuroleptic malignant syndrome (NMS) is a rare but life-threatening
      complication of neuroleptic drugs, which are used widely in head and neck cancer
      (HANC) patients who develop delirium. Methods and Results. Postoperative delirium
      in a 39-year-old man with tongue cancer was treated with haloperidol and
      chlorpromazine. Three days after the first administration of antipsychotics, the
      patient exhibited elevated body temperature, autonomic and extrapyramidal
      symptoms, and impaired consciousness. A definitive diagnosis was made using the
      research diagnostic criteria for NMS in the DSM-IV, and the antipsychotics were
      immediately discontinued. The patient was given dantrolene and bromocriptine to
      treat the NMS. The patient's hyperthermia, elevated creatinin kinase (CK), and
      muscle rigidity improved gradually, with all symptoms of NMS resolving completely
      by 13 days after the diagnosis. Conclusions. HANC surgeons must be alert for
      early signs of NMS and use antipsychotics conservatively to avoid NMS and its
      potentially fatal outcome. 

PMID- 23853729
TI  - Imaging of acute invasive fungal rhinosinusitis in a patient with gorlin syndrome
      and acute lymphocytic leukemia.
AB  - Gorlin Syndrome (GS), also known as nevoid basal cell carcinoma syndrome, is a
      rare autosomal dominant condition characterized by developmental abnormalities
      and predisposition to certain neoplasms. Acute invasive fungal rhinosinusitis
      (AIFRS) is an uncommon clinical entity characterized by high morbidity and
      mortality. In immunocompromised patients, computed tomography plays a critical
      role in screening for suspected AIFRS. However, due to the association between
      exposure to ionizing radiation and subsequent development of malignancies in
      patients with GS, patients with GS and suspected AIFRS present a unique and
      challenging clinical scenario. We present a case of a pediatric patient with GS
      and acute lymphocytic leukemia (ALL) diagnosed with AIFRS; to the best of our
      knowledge, it is the only case described in the literature. 

PMID- 23853730
TI  - Congenital hairy polyp of the palatopharyngeus muscle.
AB  - Purpose. To describe clinical, radiologic, and histological features of a
      congenital hairy polyp arising from the palatopharyngeus muscle in a neonate.
      Methods. Chart of a 2-day-old female referred to a tertiary care pediatric
      hospital for assessment of intraoral mass was reviewed. Results. The child was
      born at 32 weeks and an intraoral mass was noted. The patient was transferred to
      tertiary care children's hospital on day 2 of life. The child had increased work
      of breathing at presentation and required continuous positive airway pressure.
      Physical examination revealed a pedunculated mass which was protruding into the
      oropharynx from the nasopharynx. MRI of the lesion documented a discrete bilobed
      mass which filled the posterior nasopharynx. The mass abutted the uvula and soft
      palate; however, the mass did not appear to be arising from the soft palate.
      Intraoperative exam showed a mass arising from the right palatopharyngeus muscle
      in the superior pole region of the tonsil. Histologic examination showed
      ectodermal and mesodermal derivatives confirming congenital hairy polyp. At 8
      month followup, the surgical site was healed with no evidence of recurrent
      lesion. Conclusions. Congenital hairy polyp, though uncommon, should be
      considered in the differential diagnosis of oropharyngeal mass in neonates. 

PMID- 23853731
TI  - Gastric carcinoma with osteoclast-like giant cells coexisting with
      gastrointestinal spindle cell tumor.
AB  - Reactive multinucleated osteoclast-like giant cells (OGCs) have been described in
      a variety of neoplasms but rarely in gastric carcinomas. Reported herein is a
      case of an 81-year-old Caucasian male presented with upper abdominal pain and
      dysphagia. Esophagogastroscopy revealed an ulcerative mass and a specimen of
      subtotal gastrectomy and lower esophagectomy was sent for histologic examination.
      At the gastroesophageal junction an exophytic tumor, measured 2.2 cm in greatest
      diameter, was observed. Sections from the tumor showed gastric adenocarcinoma,
      stage pT1bpN0. Diffusely among the neoplastic cells multinucleated giant cells,
      resembling osteoclasts, were observed, which were positive for CD68, lysozyme,
      and vimentin and negative for AE1/AE3, CK8/18, hHCG, and LMP1. Moreover, in a
      random section from the gastric fundus, a spindle cell lesion, sized 0.6 cm, was
      revealed, which was positive for CD117 and CD34 antigens and was diagnosed as
      gastrointestinal stromal tumor (GIST). The presence of OGCs is an uncommon
      finding in gastric carcinomas and by analogy to breast and pancreatic carcinomas
      it could characterize a rare distinct morphological variant of gastric
      adenocarcinoma. Due to the limited number of the reported cases, the prognostic
      value of OGCs is under discussion. Furthermore, pathologists should be aware that
      incidental GIST may accompany any tumor. 

PMID- 23853732
TI  - Improvements in Behavioral Symptoms following Antibiotic Therapy in a 14-Year-Old
      Male with Autism.
AB  - This case report describes the benefits of antibiotic and antifungal therapy on
      behavior in a child with autism undergoing treatment for encopresis. Over the
      course of treatment, the child exhibited a reduction in aberrant behaviors,
      increased gastrointestinal function, and improved quality of life. 

PMID- 23853733
TI  - A Behcet's Disease Patient with Right Ventricular Thrombus, Pulmonary Artery
      Aneurysms, and Deep Vein Thrombosis Complicating Recurrent Pulmonary
      Thromboembolism.
AB  - Intracardiac thrombus, pulmonary artery aneurysms, deep vein thrombosis, and
      pulmonary thromboembolism are rarely seen symptoms of Behcet's disease. A 20-year
      old female patient was admitted for complaints of cough, fever, palpitations, and
      chest pain. On the dynamic thorax computed tomograms (CT) obtained because of
      significantly enlarged hilar structures seen on chest radiograms, aneurysmal
      dilatation of the pulmonary artery segments bilaterally, chronic thrombus with
      collapse, and consolidation substances compatible with pulmonary embolism
      involving both lower lobes have been observed. It is learned that, four years
      ago, the patient had been diagnosed with Behcet's disease and received colchicine
      treatment but not regularly. The patient was hospitalized. On the transthoracic
      echocardiogram, a thrombosis with a dimension of 4.2 * 1.6 cm was recognized in
      the right ventricle. On abdomen CT, aneurysmal iliac veins and deep vein thrombus
      on Doppler ultrasonograms were diagnosed. At the controls after three months of
      immunosuppressive and anticoagulant therapies, some clinical and radiological
      improvements were recognized. The patient suspended the treatment for a month and
      the thrombus recurred. We present our case in order to show the effectiveness of
      immunosuppressive and anticoagulant therapies and rarely seen pulmonary
      thromboembolism in recurrent Behcet's disease. 

PMID- 23853734
TI  - The Demise of Poskanzer and Schwab's Influenza Theory on the Pathogenesis of
      Parkinson's Disease.
AB  - In 1961, David C. Poskanzer and Robert S. Schwab presented a paper, "Studies in
      the epidemiology of Parkinson's disease predicting its disappearance as a major
      clinical entity by 1980." This paper introduced the hypothesis that Parkinson's
      disease was derived from a single aetiology, the influenza virus. We review the
      original Poskanzer and Schwab hypothesis that Parkinson's disease was based on
      the association between the 1918-19 influenza epidemic and the later observation
      of Parkinsonism in some influenza sufferers. We also further explore the
      prediction that Parkinson's disease would totally disappear as an entity once
      original influenza victims were all deceased. Current research has revealed that
      there are many potential causes and factors important in the occurrence of
      Parkinson's disease, postencephalitic Parkinsonism, and encephalitis lethargica.
      Poskanzer and Schwab presented a novel hypothesis; however, it was proven false
      by a combination of research and time. 

PMID- 23853736
TI  - Limitations of the use of pressure waves to verify correct epidural needle
      position in dogs.
AB  - The use of pressure waves to confirm the correct position of the epidural needle
      has been described in several domestic species and proposed as a valid
      alternative to standard methods, namely, control radiographic exam and
      fluoroscopy. The object of this retrospective clinical study was to evaluate the
      sensitivity of the epidural pressure waves as a test to verify the correct needle
      placement in the epidural space in dogs, in order to determine whether this
      technique could be useful not only in the clinical setting but also when certain
      knowledge of needle's tip position is required, for instance when performing
      clinical research focusing on epidural anaesthesia. Of the 54 client-owned dogs
      undergoing elective surgeries and enrolled in this retrospective study, only 45%
      showed epidural pressure waves before and after epidural injection. Twenty-six
      percent of the animals showed epidural pressure waves only after the injection,
      whereas 29% of the dogs showed epidural pressure waves neither before nor after
      injection and were defined as false negatives. Our results show that the epidural
      pressure wave technique to verify epidural needle position lacks sensitivity,
      resulting in many false negatives. As a consequence, the applicability of this
      technique is limited to situations in which precise, exact knowledge of the
      needle's tip position is not mandatory. 

PMID- 23853735
TI  - Metabotropic glutamate receptors for Parkinson's disease therapy.
AB  - Excessive glutamatergic signalling within the basal ganglia is implicated in the
      progression of Parkinson's disease (PD) and inthe emergence of dyskinesia
      associated with long-term treatment with L-DOPA. There is considerable research
      focus on the discovery and development of compounds that modulate glutamatergic
      signalling via glutamate receptors, as treatments for PD and L-DOPA-induced
      dyskinesia (LID). Although initial preclinical studies with ionotropic glutamate
      receptor antagonists showed antiparkinsonian and antidyskinetic activity, their
      clinical use was limited due to psychiatric adverse effects, with the exception
      of amantadine, a weak N-methyl-d-aspartate (NMDA) antagonist, currently used to
      reduce dyskinesia in PD patients. Metabotropic receptor (mGlu receptor)
      modulators were considered to have a more favourable side-effect profile, and
      several agents have been studied in preclinical models of PD. The most promising
      results have been seen clinically with selective antagonists of mGlu5 receptor
      and preclinically with selective positive allosteric modulators of mGlu4
      receptor. The growing understanding of glutamate receptor crosstalk also raises
      the possibility of more precise modulation of glutamatergic transmission, which
      may lead to the development of more effective agents for PD. 

PMID- 23853737
TI  - Effect of Addition of Taurine on the Liquid Storage (5 degrees C) of Mithun (Bos
      frontalis) Semen.
AB  - The present study was undertaken to assess the effect of taurine on sperm
      motility, viability, total sperm abnormalities, acrosomal and plasma membrane
      integrity, enzymatic profiles such as reduced glutathione (GSH), glutathione
      peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT), and biochemical
      profiles such as cholesterol efflux and malondialdehyde (MDA) production. A total
      of 50 ejaculates were collected twice a week from 8 mithun bulls, and semen was
      split into 4 equal aliquots and diluted with the TEYC extender. Group 1: semen
      was without additives (control); groups 2 to 4: semen was diluted with 25 mM, 50
      mM, and 100 mM of taurine, respectively. Seminal parameters and enzymatic and
      biochemical profiles were assessed at 5 degrees C. Inclusion of taurine into
      diluent resulted in significant (P < 0.05) decreases in percentages of dead
      spermatozoa, abnormal spermatozoa, and acrosomal abnormalities after liquid
      storage compared with the control group. Additionally, taurine at 50 mM has
      significant improvement in quality of mithun semen than taurine at 25 or 100 mM
      stored in in vitro at 5 degrees C. It was concluded that the possible protective
      effects of taurine on sperm parameters are from enhancing the function of
      antioxidant enzymes, preventing efflux of cholesterol from cell membranes and
      decreased MDA production. 

PMID- 23853738
TI  - Efficacy of Seabuckthorn (Hippophae rhamnoides) Oil vis-a-vis Other Standard
      Drugs for Management of Gastric Ulceration and Erosions in Dogs.
AB  - The study was conducted on 20 adult healthy medium-sized mongrel dogs. Injection
      of dexamethasone @ 1 mg/kg, IV, b.i.d., was administered to create gastric
      ulcerations and erosions. Thereafter all the animals were randomly divided into 5
      equal treatment groups. Animals of groups I, II, III, IV, and V were treated with
      oral administration of lansoprazole @ 1.5 mg/kg, sucralfate @ 1 g/animal,
      misoprostol @ 10 ug/kg, famotidine @ 1 mg/kg, and Seabuckthorn seed oil @ 5
      mL/animal, twice a day, respectively. Gastroendoscopically, complete healing of
      GUE lesions was earliest in Seabuckthorn- (SBT-) oil-treated group (7.5 +/- 0.87)
      followed by famotidine (8.25 +/- 1.44), lansoprazole (9.00 +/- 1.23), misoprostol
      (10.50 +/- 1.50), and sucralfate (13.50 +/- 0.87), respectively. A marked
      improvement in appetite was observed in all animals. Melena was continued till
      day 3 in SBT group, day 6 in lansoprazole- and famotidine-treated animals, and
      day 9 in sucralfate and misoprostol group animals. Fecal occult blood test was
      positive in all animals till there was endoscopic evidence of gastric bleeding.
      Hematological parameters improved markedly towards the end of the study. Serum
      biochemical parameters remained within normal physiological limits throughout the
      study. It is concluded that Seabuckthorn oil was the best therapeutic agent for
      dexamethasone-induced GUE in dogs followed by famotidine, lansoprazole,
      misoprostol, and sucralfate. 

PMID- 23853739
TI  - Interest in Anesthesia as Reflected by Keyword Searches using Common Search
      Engines.
AB  - BACKGROUND: Since current general interest in anesthesia is unknown, we analyzed
      internet keyword searches to gauge general interest in anesthesia in comparison
      with surgery and pain. METHODS: The trend of keyword searches from 2004 to 2010
      related to anesthesia and anaesthesia was investigated using Google Insights for
      Search. The trend of number of peer reviewed articles on anesthesia cited on
      PubMed and Medline from 2004 to 2010 was investigated. The average cost on
      advertising on anesthesia, surgery and pain was estimated using Google AdWords.
      Searching results in other common search engines were also analyzed. Correlation
      between year and relative number of searches was determined with p< 0.05
      considered statistically significant. RESULTS: Searches for the keyword
      "anesthesia" or "anaesthesia" diminished since 2004 reflected by Google Insights
      for Search (p< 0.05). The search for "anesthesia side effects" is trending up
      over the same time period while the search for "anesthesia and safety" is
      trending down. The search phrase "before anesthesia" is searched more frequently
      than "preanesthesia" and the search for "before anesthesia" is trending up. Using
      "pain" as a keyword is steadily increasing over the years indicated. While
      different search engines may provide different total number of searching results
      (available posts), the ratios of searching results between some common keywords
      related to perioperative care are comparable, indicating similar trend. The peer
      reviewed manuscripts on "anesthesia" and the proportion of papers on "anesthesia
      and outcome" are trending up. Estimates for spending of advertising dollars are
      less for anesthesia-related terms when compared to that for pain or surgery due
      to relative smaller number of searching traffic. CONCLUSIONS: General interest in
      anesthesia (anaesthesia) as measured by internet searches appears to be
      decreasing. Pain, preanesthesia evaluation, anesthesia and outcome and side
      effects of anesthesia are the critical areas that anesthesiologists should focus
      on to address the increasing concerns.

PMID- 23853740
TI  - Memory Loss, Alzheimer's Disease and General Anesthesia: A Preoperative Concern.
AB  - BACKGROUND: The long-term cognitive effects of general anesthesia are under
      intense scrutiny. Here we present 5 cases from 2 academic institutions to analyze
      some common features where the patient's or the patient family member has made a
      request to address their concern on memory loss, Alzheimer's disease and general
      anesthesia before surgery. METHODS: Records of anesthesia consultation separate
      from standard preoperative evaluation were retrieved to identify consultations
      related to memory loss and Alzheimer's disease from the patient and/or patient
      family members. The identified cases were extensively reviewed for features in
      common. We used Google(r) (http://www. google.com/) to identify available online
      information using "anesthesia memory loss" as a search phrase. RESULTS: Five
      cases were collected as a specific preoperative consultation related to memory
      loss, Alzheimer's disease and general anesthesia from two institutions. All of
      the individuals either had perceived memory impairment after a prior surgical
      procedure with general anesthesia or had a family member with Alzheimer's
      disease. They all accessed public media sources to find articles related to
      anesthesia and memory loss. On May 2nd, 2011, searching "anesthesia memory loss"
      in Google yielded 764,000 hits. Only 3 of the 50 Google top hits were from peer
      reviewed journals. Some of the lay media postings made a causal association
      between general anesthesia and memory loss and/or Alzheimer's disease without
      conclusive scientific literature support. CONCLUSION: The potential link between
      memory loss and Alzheimer's disease with general anesthesia is an important
      preoperative concern from patients and their family members. This concern arises
      from individuals who have had history of cognitive impairment or have had a
      family member with Alzheimer disease and have tried to obtain information from
      public media. Proper preoperative consultation with the awareness of the lay
      literature can be useful in reducing patient and patient family member's
      preoperative anxiety related to this concern.

PMID- 23853741
TI  - An ICU Preanesthesia Evaluation Form Reduces Missing Preoperative Key
      Information.
AB  - BACKGROUND: A comprehensive preoperative evaluation is critical for providing
      anesthetic care for patients from the intensive care unit (ICU). There has been
      no preoperative evaluation form specific for ICU patients that allows for a rapid
      and focused evaluation by anesthesia providers, including junior residents. In
      this study, a specific preoperative form was designed for ICU patients and
      evaluated to allow residents to perform the most relevant and important
      preoperative evaluations efficiently. METHODS: The following steps were utilized
      for developing the preoperative evaluation form: 1) designed a new preoperative
      form specific for ICU patients; 2) had the form reviewed by attending physicians
      and residents, followed by multiple revisions; 3) conducted test releases and
      revisions; 4) released the final version and conducted a survey; 5) compared data
      collection from new ICU form with that from a previously used generic form. Each
      piece of information on the forms was assigned a score, and the score for the
      total missing information was determined. The score for each form was presented
      as mean +/- standard deviation (SD), and compared by unpaired t test. A P value <
      0.05 was considered statistically significant. RESULTS: Of 52 anesthesiologists
      (19 attending physicians, 33 residents) responding to the survey, 90% preferred
      the final new form; and 56% thought the new form would reduce perioperative risk
      for ICU patients. Forty percent were unsure whether the form would reduce
      perioperative risk. Over a three month period, we randomly collected 32 generic
      forms and 25 new forms. The average score for missing data was 23 +/- 10 for the
      generic form and 8 +/- 4 for the new form (P = 2.58E-11). CONCLUSIONS: A
      preoperative evaluation form designed specifically for ICU patients is well
      accepted by anesthesia providers and helped to reduce missing key preoperative
      information. Such an approach is important for perioperative patient safety.

PMID- 23853743
TI  - Modelling the performance of USV manoeuvring and target tracking: an approach
      using frequency modulated continuous wave radar rotary system.
AB  - The performance of frequency modulated continuous wave (FMCW) radar in tracking
      targets is presented and analysed. Obstacle detection, target tracking and radar
      target tracking performance models are developed and were used to investigate and
      to propose ways of improving the autonomous motion of unmanned surface vehicle
      (USV). Possible factors affecting the performance of FMCW radar in tracking
      targets are discussed and analysed. 

PMID- 23853742
TI  - The Emerging Field of Human Social Genomics.
AB  - Although we generally experience our bodies as being biologically stable across
      time and situations, an emerging field of research is demonstrating that external
      social conditions, especially our subjective perceptions of those conditions, can
      influence our most basic internal biological processes-namely, the expression of
      our genes. This research on human social genomics has begun to identify the types
      of genes that are subject to social-environmental regulation, the neural and
      molecular mechanisms that mediate the effects of social processes on gene
      expression, and the genetic polymorphisms that moderate individual differences in
      genomic sensitivity to social context. The molecular models resulting from this
      research provide new opportunities for understanding how social and genetic
      factors interact to shape complex behavioral phenotypes and susceptibility to
      disease. This research also sheds new light on the evolution of the human genome
      and challenges the fundamental belief that our molecular makeup is relatively
      stable and impermeable to social-environmental influence.

PMID- 23853744
TI  - Principled missing data methods for researchers.
AB  - The impact of missing data on quantitative research can be serious, leading to
      biased estimates of parameters, loss of information, decreased statistical power,
      increased standard errors, and weakened generalizability of findings. In this
      paper, we discussed and demonstrated three principled missing data methods:
      multiple imputation, full information maximum likelihood, and expectation
      maximization algorithm, applied to a real-world data set. Results were contrasted
      with those obtained from the complete data set and from the listwise deletion
      method. The relative merits of each method are noted, along with common features
      they share. The paper concludes with an emphasis on the importance of statistical
      assumptions, and recommendations for researchers. Quality of research will be
      enhanced if (a) researchers explicitly acknowledge missing data problems and the
      conditions under which they occurred, (b) principled methods are employed to
      handle missing data, and (c) the appropriate treatment of missing data is
      incorporated into review standards of manuscripts submitted for publication. 

PMID- 23853745
TI  - Behavior believability in virtual worlds: agents acting when they need to.
AB  - Believability has been a perennial goal for the intelligent virtual agent
      community. One important aspect of believability largely consists in
      demonstrating autonomous behavior, consistent with the agent's personality and
      motivational state, as well as the world conditions. Autonomy, on behalf of the
      agent, implies the existence of an internal structure and mechanism that allows
      the agent to have its own needs and interests, based on which the agent will
      dynamically select and generate goals that will in turn lead to self-determined
      behavior. Intrinsic motivation allows the agent to function and demonstrate
      behavior, even when no external stimulus is present, due to the constant change
      of its internal emotional and physiological state. The concept of motivation has
      already been investigated by research works on intelligent agents, trying to
      achieve autonomy. The current work presents an architecture and model to
      represent and manage internal driving factors in intelligent virtual agents,
      using the concept of motivations. Based on Maslow and Alderfer's bio
      psychological needs theories, we present a motivational approach to represent
      human needs and produce emergent behavior through motivation synthesis.
      Particular attention is given to basic, physiological level needs, which are the
      basis of behavior and can produce tendency to action even when there is no other
      interaction with the environment. 

PMID- 23853746
TI  - Demographic characterization and social patterns of the Neotropical pampas deer.
AB  - The most endangered subspecies of pampas deer Ozotoceros bezoarticus uruguayensis
      is an endemic cervidae of the Uruguayan temperate grasslands. The aim of our
      study was to assess the demographic trends, grouping structure and dynamic of
      this small and isolated population. We surveyed the population during seven years
      and detected an average of 117 (+ 72.7 SD) individuals (44 censuses). The average
      population structure observed was 55% adult females, 34% adult males, 10%
      juveniles, and 1% fawns, with a low recruitment rate of 0.11. The pampas deer is
      a gregarious cervidae with 62% of individuals being observed within groups of at
      least three animals. Nevertheless we observed substantial differences on group
      size and composition based on sex, reproductive status, season and trophic
      resources availability. The population dynamics showed significant changes around
      the year in the sexual aggregation-segregation pattern, corresponding with
      reproductive and physiological status. The mean density on this population (11
      deer/ km(2)) is the highest reported for the species. Comparable data, from other
      populations, showed a significant correlation between density and sex ratio, with
      a reduction in the proportion of males with higher deer densities. An action plan
      for this endangered population should include initiatives involving private
      landowners, and guidelines to improve the deer habitat. 

PMID- 23853747
TI  - Correlation between article download and citation figures for highly accessed
      articles from five open access oncology journals.
AB  - Different approaches can be chosen to quantify the impact and merits of
      scientific oncology publications. These include source of publication (including
      journal reputation and impact factor), whether or not articles are cited by
      others, and access/download figures. When relying on citation counts, one needs
      to obtain access to citation databases and has to consider that results differ
      from one database to another. Accumulation of citations takes time and their
      dynamics might differ from journal to journal and topic to topic. Therefore, we
      wanted to evaluate the correlation between citation and download figures,
      hypothesising that articles with fewer downloads also accumulate fewer citations.
      Typically, publishers provide download figures together with the article. We
      extracted and analysed the 50 most viewed articles from 5 different open access
      oncology journals. For each of the 5 journals and also all journals combined,
      correlation between number of accesses and citations was limited (r = 0.01-0.30).
      Considerable variations were also observed when analyses were restricted to
      specific article types such as reviews only (r = 0.21) or case reports only (r =
      0.53). Even if year of publication was taken into account, high correlation
      coefficients were the exception from the rule. In conclusion, downloads are not a
      universal surrogate for citation figures. 

PMID- 23853748
TI  - Enterococcus faecalis FK-23 affects alveolar-capillary permeability to attenuate
      leukocyte influx in lung after influenza virus infection.
AB  - Infection with influenza A virus, one of the most common life-threatening
      viruses, causes the accumulation of inflammatory cells in the lung, which is
      directly correlated with influenza-associated morbidity and mortality. In this
      study, we investigated the potential of lysozyme-treated Enterococcus faecalis FK
      23 (LFK) to prevent influenza in influenza virus-infected mice. C57BL/6N mice
      were orally administered LFK and intranasally infected with influenza virus
      A/Puerto Rico/8/34 (H1N1) at lethal doses. After infection with influenza A
      virus, the survival rate of the LFK-administered mice was significantly higher
      than that of saline-administered mice. Staining of lung sections with hematoxylin
      eosin, and cell counts of lung and bronchoalveolar lavage fluid showed that oral
      administration of LFK suppressed the excessive infiltration of leukocytes into
      the lung after viral infection. Extravasation assay revealed that the arrest was
      mediated by modulation of pulmonary alveolar-capillary permeability. Expression
      levels of genes involved in matrix degradation, which are correlated with
      vascular permeability, were downregulated in LFK-administered mice. These
      findings suggest that stabilizing the integrity of the alveolar-capillary barrier
      by the administration of LFK improves survival rate. 

PMID- 23853749
TI  - pKa determination of oxysophocarpine by reversed - phase high performance liquid
      chromatography.
AB  - BACKGROUND: In this study, a RP - HPLC method was applied for determination of
      pKa value by using the dependence of the capacity factor (k) on the pH of the
      mobile phase for oxysophocarpine (OSP). FINDINGS: The effect of the mobile phase
      composition on the ionization constant was studied by measuring the pKa value at
      different MeOH concentrations, ranging from 10 to 20% (v/v). Based on all pH - k
      curves plotted and pH values at inflection point calculated, experimental pKa
      value obtained for oxysophocarpine was 6.5. CONCLUSION: This method was
      successfully applied to realize low sample consumption, rapid sample throughput,
      high sensitivity and precision.

PMID- 23853750
TI  - Impact of closed-system drug transfer device on exposure of environment and
      healthcare provider to cyclophosphamide in Japanese hospital.
AB  - In spite of current recommended safe handling procedures, the potential for the
      exposure of healthcare providers to hazardous drugs exists in the workplace. A
      reliance on biological safety cabinets to provide total protection against the
      exposure to hazardous drugs is insufficient. Preventing workplace contamination
      is the best strategy to minimize cytotoxic drug exposure in healthcare providers.
      This study was conducted to compare surface contamination and personnel exposure
      to cyclophosphamide before and after the implementation of a closed-system drug
      transfer device, PhaSeal, under the influence of cleaning according to the
      Japanese guidelines. Personnel exposure was evaluated by collecting 24 h urine
      samples from 4 pharmacists. Surface contamination was assessed by the wiping
      test. Four of 6 wipe samples collected before PhaSeal indicated a detectable
      level of cyclophosphamide. About 7 months after the initiation of PhaSeal, only
      one of 6 wipe samples indicated a detectable level of cyclophosphamide. Although
      all 4 employees who provided urine samples had positive results for the urinary
      excretion of cyclophosphamide before PhaSeal, these levels returned to minimal
      levels in 2 pharmacists after PhaSeal. In combination with the biological safety
      cabinet and cleaning according to the Japanese guidelines, PhaSeal further
      reduces surface contamination and healthcare providers exposure to
      cyclophosphamide to almost undetectable levels. 

PMID- 23853751
TI  - Comparative effectiveness of strategies to prevent weight gain among women with
      and at risk for breast cancer: a systematic review.
AB  - BACKGROUND: Obesity affects cancer risk and treatment outcomes. Preventing weight
      gain may prevent some cancers, improve cancer outcomes, reduce cancer recurrence
      and increase cancer-related survival. We performed a systematic review to
      identify strategies to prevent weight gain in individuals with or at risk for
      breast cancer. FINDINGS: We included 2 studies from 27,879 citations. In
      premenopausal women at risk for breast cancer, a low fat diet prevented weight
      gain at 12 months. Among women with breast cancer, effective strategies to
      prevent weight gain included low-fat dietary counseling with self-management
      techniques. One trial reported on cancer outcomes, mortality and adverse events.
      Low-fat dietary counseling wilth self-management techniques lowers the risk
      breast cancer relapse by 24% compared with less intensive counseling with
      maintenance of nutritional status goal. There was no difference in overall
      mortality and no adverse events were observed. CONCLUSION: Limited evidence
      suggests that women with or at risk for breast cancer may successfully employ
      dietary and exercise strategies to prevent weight gain for at least one year. Low
      fat dietary counseling may improve cancer outcomes in women with breast cancer.
      Future studies should confirm these findings and evaluate the impact of weight
      gain prevention on cancer incidence, recurrence and survival.

PMID- 23853752
TI  - Improved treatment of Asthma by using natural sources of antioxidants.
AB  - ABSTRACT: A combined composition of the extracted powders from Hippocampus kuda
      and Rhizoma Homalomenae together with honey in a form of medical pill (named as
      BRONAS) for the treatment of asthma has thoroughly been investigated under this
      study. BRONAS has shown its high anti-inflammatory effects and strong inhibition
      upon the pathogenesis of asthma. In comparison with other treatments without
      using BRONAS, the restoration of patients' health was improved by a factor of 2
      3. CLINICAL TRIALS WITH ACTR NUMBER: ACTRN12612000766819.

PMID- 23853753
TI  - Comparison of clinical features and outcomes of staphylococcus aureus vertebral
      osteomyelitis caused by methicillin-resistant and methicillin-sensitive strains.
AB  - The causative organism of vertebral osteomyelitis (VO) was almost exclusively
      Staphylococcus aureus. The purpose of this study was to delineate the differences
      in clinical features and outcomes between patients with methicillin-resistant
      Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus
      (MSSA) VO. This study retrospectively reviewed 85 consecutive patients with VO
      treated between 2005 and 2011. Surgical site infections were excluded. Diagnosis
      was made by cultures of either blood or biopsied samples. We identified 16 cases
      of MRSA VO and 14 cases of MSSA VO. The average follow-up period was 18.5 months.
      Clinical features and outcomes were analyzed. Males were more likely to have MRSA
      VO than MSSA VO (87.5% vs. 35.7%). In regards to the number of co-morbidities,
      patients with MRSA VO had significantly more co-mobidities than patients with
      MSSA VO. Additionally, the rate of patients who underwent surgical procedure
      (excluding spinal surgeries in the affected region) within 3 months were
      significantly higher in the MRSA VO group than the MSSA VO group (56.3% vs.
      14.3%). White blood cell counts and C-reactive protein levels in patients with
      both strains significantly improved 4 weeks after the initial treatment compared
      with the pretreatment values. The recurrence rate within 6 months tended to be
      higher for MRSA VO (37.5% vs. 7.1%), but no significant difference in mortality
      was observed between the two VO types. In conclusion, male sex, multiple co
      morbidities and previous non-spine surgery were significant risk factors for VO
      due to MRSA as compared to MSSA. The recurrence rate within 6 months tended to be
      higher for MRSA VO. Patients with MRSA VO should be monitored carefully for
      recurrence by sequential clinical, radiographic, and laboratory examinations
      during the treatment course. 

PMID- 23853754
TI  - Health insurance mediation of the Mexican American non-Hispanic white disparity
      on early breast cancer diagnosis.
AB  - We examined health insurance mediation of the Mexican American (MA) non-Hispanic
      white (NHW) disparity on early breast cancer diagnosis. Based on social capital
      and barrio advantage theories, we hypothesized a 3-way ethnicity by poverty by
      health insurance interaction, that is, that 2-way poverty by health insurance
      interaction effects would differ between ethnic groups. We secondarily analyzed
      registry data for 303 MA and 3,611 NHW women diagnosed with breast cancer between
      1996 and 2000 who were originally followed until 2011. Predictors of early, node
      negative (NN) disease at diagnosis were analyzed. Socioeconomic data were
      obtained from the 2000 census to categorize neighborhood poverty: high (30% or
      more of the census tract households were poor), middle (5% to 29% poor) and low
      (less than 5% poor). Barrios were neighborhoods where 50% or more of the
      residents were MA. Primary health insurers were Medicaid, Medicare, private or
      none. MA women were 13% less likely to be diagnosed early with NN disease (RR =
      0.87), but this MA-NHW disparity was completely mediated by the main and
      interacting effects of health insurance. Advantages of health insurance were
      largest in low poverty neighborhoods among NHW women (RR = 1.20) while among MA
      women they were, paradoxically, largest in high poverty, MA barrios (RR = 1.45).
      Advantages of being privately insured were observed for all. Medicare seemed
      additionally instrumental for NHW women and Medicaid for MA women. These findings
      are consistent with the theory that more facilitative social and economic capital
      is available to MA women in barrios and to NHW women in more affluent
      neighborhoods. It is there that each respective group of women is probably best
      able to absorb the indirect and direct, but uncovered, costs of breast cancer
      screening and diagnosis. 

PMID- 23853755
TI  - Interactive network analysis of the plasma amino acids profile in a mouse model
      of hyperglycemia.
AB  - Amino acids are a group of metabolites that are important substrates for protein
      synthesis, are important as signaling molecules and play central roles as highly
      connected metabolic hubs, and therefore, there are many reports that describe
      disease-specific abnormalities in plasma amino acids profile. However, the causes
      of progression from a healthy control to a manifestation of the plasma amino acid
      changes remain obscure. Here, we extended the plasma amino acids profile to
      relationships that have interactive properties, and found remarkable differences
      in the longitudinal transition of hyperglycemia as a diabetes emergency. What is
      especially important is to understand pathogenesis for better treatment and early
      diagnosis of diabetes. In this study, we performed interactive analysis using
      time course data of the plasma samples of AKITA mice, which develop
      hyperglycemia. Primarily, we decided to analyze the interactive property of amino
      acids which had highly significant association with hyperglycemia, namely
      alanine, glycine, leucine, isoleucine and valine. Next, we inferred the
      interactive network structure, which reproduces the actual time course within an
      error allowance of 10% using an S-system model (a conceptual mathematical model
      for analyzing and simulating networks). The emphasis of this study was altered
      interactions of plasma amino acids that show stabilizing and destabilizing
      features in a variety of clinical settings. By performing sensitivity analysis,
      the most dominant relations in this network were selected; the control paths from
      glycine to isoleucine in healthy control and from alanine to glycine in
      hyperglycemia. This result is in good agreement with the biological knowledge
      regarding branched-chain amino acids, and suggests the biological importance of
      the effect from alanine to glycine. 

PMID- 23853756
TI  - Ontogenesis from embryo to juvenile and salinity tolerance of Japanese devil
      stinger Inimicus japonicus during early life stage.
AB  - Embryonic development and morphological characteristics of Japanese devil stinger
      Inimicus japonicus during early life stage were investigated. Larvae were hatched
      out 50 h after fertilization at temperature 21 degrees C. Total length of the
      newly hatched larva was 4.03 mm, the mouth of the larva opened at 3 days after
      hatching (DAH), and the yolk sac of the larva disappeared at 5 DAH. After
      hatching, the pectoral fin first developed, then the tail fin, dorsal fin, anal
      fin and pelvic fin continuously developed, and all fins formed completely at 15
      DAH. The metamorphosis was complete at 25 DAH, and the body color and habit of
      the metamorphosed individuals were different from the larvae. At 30 DAH, the
      morphology and habit of the juveniles were the same to adults. In order to
      determine the suitable salinity for larviculture of I. japonicus, salinity
      tolerance at different early developmental stages was compared in terms of the
      survival activity index (SAI) and mean survival time (MST). The results indicated
      that salinity tolerance varied with development stages. The optimum salinity
      range for newly hatched larvae was 10-250/00. Larvae showed low tolerance to low
      salinity (50/00) before the mouth opened, and the suitable salinities for the
      larvae with open mouth, yolk-sac larvae, post yolk-sac larvae were 10-150/00. The
      flexion larvae showed a wider salinity tolerance with range of 5-200/00. After
      metamorphosis, the juveniles showed a preferable adaptability of salinities of 15
      200/00. The SAI and MST of individuals at various stages under different salinity
      conditions were positively correlated. 

PMID- 23853757
TI  - Enhancing nitrilase production from Fusarium proliferatum using response surface
      methodology.
AB  - The individual and interactive effects of three independent variables i.e. carbon
      source (glucose), nitrogen source (sodium nitrate) and inducer (epsilon
      caprolactam) on nitrilase production from Fusarium proliferatum were investigated
      using design of experiments (DOE) methodology. Response surface methodology (RSM)
      was followed to generate the process model and to obtain the optimal conditions
      for maximum nitrilase production. Based on central composite design (CCD) a
      quadratic model was found to fit the experimental data (p<0.0001) and maximum
      activity of 59.0U/g biomass was predicted at glucose concentration (53.22 g/l),
      sodium nitrate (2.31 g/l) and epsilon-caprolactam (3.58 g/l). Validation
      experiments were carried out under the optimized conditions for verification of
      the model. The nitrilase activity of 58.3U/g biomass obtained experimentally
      correlated to the predicted activity which proves the authenticity of the model.
      Overall 2.24 fold increase in nitrilase activity was achieved as compared to the
      activity before optimization (26U/g biomass). 

PMID- 23853758
TI  - Estimating long-run equilibrium real exchange rates: short-lived shocks with long
      lived impacts on Pakistan.
AB  - The purpose of this study is to investigate the factors that affect real exchange
      rate volatility for Pakistan through the co-integration and error correction
      model over a 30-year time period, i.e. between 1980 and 2010. The study employed
      the autoregressive conditional heteroskedasticity (ARCH), generalized
      autoregressive conditional heteroskedasticity (GARCH) and Vector Error Correction
      model (VECM) to estimate the changes in the volatility of real exchange rate
      series, while an error correction model was used to determine the short-run
      dynamics of the system. The study is limited to a few variables i.e.,
      productivity differential (i.e., real GDP per capita relative to main trading
      partner); terms of trade; trade openness and government expenditures in order to
      manage robust data. The result indicates that real effective exchange rate (REER)
      has been volatile around its equilibrium level; while, the speed of adjustment is
      relatively slow. VECM results confirm long run convergence of real exchange rate
      towards its equilibrium level. Results from ARCH and GARCH estimation shows that
      real shocks volatility persists, so that shocks die out rather slowly, and
      lasting misalignment seems to have occurred. 

PMID- 23853759
TI  - Incidence of synchronous and metachronous adrenal metastases following tumor
      nephrectomy in renal cell cancer patients: a retrospective bi-center analysis.
AB  - INTRODUCTION: Synchronous adrenalectomy has become dispensable since
      retrospective studies have demonstrated no survival benefit when preoperative
      imaging was normal. The aim of this large bi-institutional study was to determine
      the appearance of synchronous and metachronous metastases to the adrenal gland as
      detected by computed tomography and positron emission tomography or magnetic
      resonance imaging with consecutive surgical removal of suspicious lesions.
      MATERIALS AND METHODS: We retrospectively reviewed the clinico-pathological
      records of 2720 patients from two urological centers who underwent radical or
      partial nephrectomy due to kidney cancer disease. Synchronous adrenalectomy was
      carried out in 548 of all cases (20.2%). Metachronous adrenalectomy was performed
      in 24 cases due to suspicious imaging in follow-up. RESULTS: Metastatic spread in
      patients with synchronous adrenalectomy was found in 29/548 cases (5.3%), as
      suspected. In metachronous procedures positive pathological results were found in
      24 of 24 cases. Among them 54% of all tumor recurrences were detected in the
      contralateral adrenal gland. CONCLUSIONS: In case of preoperative suspicious
      imaging an intraoperative frozen section should be performed. Radiological
      investigations are of high diagnostic value for detecting metachronous tumor
      growth into the adrenal gland. Surgery in this scenario should be recommended due
      to the high malignancy rate reported here.

PMID- 23853760
TI  - Excessive milk production during breast-feeding prior to breast cancer diagnosis
      is associated with increased risk for early events.
AB  - Breast-feeding is a known protective factor against breast cancer. Breast-feeding
      duration is influenced by hormone levels, milk production, and lifestyle factors.
      The aims were to investigate how breast-feeding duration and milk production
      affected tumor characteristics and risk for early breast cancer events in primary
      breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in
      Lund, Sweden, took part in an ongoing prospective cohort study. Data were
      extracted from questionnaires, pathology reports, and patients' charts from 592
      patients without preoperative treatment. Breast-feeding duration <=12 months of
      the first child was associated with higher frequency of ER+/PgR+ tumors (P=0.02).
      Median follow-up time was 4.9 years. Higher risk for early events was observed
      for breast-feeding duration of first child >12 months (LogRank P=0.001), total
      breast-feeding duration >12 months (LogRank P=0.008), as well as 'excessive milk
      production' during breast-feeding of the first child (LogRank P=0.001). Patients
      with 'almost no milk production' had no events. In a multivariable model
      including both 'excessive milk production' and breast-feeding duration of the
      first child >12 months, both were associated with a two-fold risk for early
      events, adjusted HRs 2.33 (95% CI: 1.25-4.36) and 2.39 (0.97-5.85), respectively,
      while total breast-feeding duration was not. 'Excessive milk production' was
      associated with a two-fold risk of early distant metastases, adjusted HR 2.59
      (1.13-5.94), but not duration. In conclusion, 'excessive milk production' during
      breast-feeding was associated with higher risk for early events independent of
      tumor characteristics, stressing the need to consider host factors in the
      evaluation of prognostic markers. 

PMID- 23853761
TI  - The Contribution of the Framingham Heart Study to Gene Identification for
      Cardiovascular Risk Factors and Coronary Heart Disease.
AB  - Genome-wide association studies have been published since 2005 and remain
      exemplary in translating knowledge fostered by the human genome project into
      genomic lessons on health and disease. Although our understanding of the basis of
      complex disease remains by far incomplete, the knowledge of the genetic basis of
      cardiovascular risk factors and their end organ damage has been significantly
      improved. The Framingham Heart Study was one of the earliest population-based
      studies to apply genomic methods and is an important contributor to large disease
      based consortia as the International Consortium for Blood Pressure Genome-Wide
      Association Studies (ICBP), the Global Lipids Genetics Consortium (GLGC), the
      DIAbetes Genetics Replication And Meta-analysis consortium (DIAGRAM), and the
      Coronary ARtery DIsease Genome-wide Replication And Meta-Analysis consortium
      (CARDIoGRAM). The variability of these principal cardiovascular risk factors is
      to large extent genetic and knowledge on the genetic basis originated largely
      from analysis of monogenic disease in rare syndromes before the use of genome
      wide, common SNP analysis. Genome-wide association studies have identified ~45
      common variants associated with systolic- and diastolic blood pressure, ~65
      common variants for type 2 diabetes and ~95 common variants for lipid traits. One
      major end organ damage is coronary heart disease and ~25 loci could be shown to
      be associated. Risk scores using multiple cardiovascular risk factor SNPs are
      clearly correlated with cardiovascular outcome. This review summarizes recent
      findings by genome-wide association studies and the contributions by the
      Framingham Heart Study on the basis of seminal articles and gives an outlook on
      some of the future experiments.

PMID- 23853763
TI  - Sense of coherence of reindeer herders and other Samis in comparison to other
      Swedish citizens.
AB  - BACKGROUND: Samis are indigenous people in north Europe. In the territory called
      Sapmi (Lapland), reindeer herding is the traditional base for the Sami economy.
      The relation between living conditions and positive health of the Swedish Samis
      has been sparsely studied. As health is closely linked to sense of coherence
      (SOC), an understanding of the background factors to SOC may contribute knowledge
      that might be useful in promoting living conditions and health. METHODS: The
      study examines relations between the level of SOC and background factors from
      surveys in a Sami population (n=613) in comparison to a non-Sami population
      (n=525) in Sweden, and in comparison between 2 subsamples of Samis, that is,
      herders and non-herders. RESULTS: There are more similarities than differences
      between the Sami and non-Sami populations. However, dividing the Sami population,
      reindeer herders had significantly lower SOC, and in specific the subcomponent
      manageability, that is, less ability to use available resources to meet different
      demands in life, compared to non-herders. CONCLUSIONS: In addition to age and
      health, predictors of SOC are related to the life form of reindeer husbandry and
      the belonging to the herding community.

PMID- 23853762
TI  - Reorganisation of brain networks in frontotemporal dementia and progressive
      supranuclear palsy.
AB  - The disruption of large-scale brain networks is increasingly recognised as a
      consequence of neurodegenerative dementias. We assessed adults with behavioural
      variant frontotemporal dementia and progressive supranuclear palsy using
      magnetoencephalography during an auditory oddball paradigm. Network connectivity
      among bilateral temporal, frontal and parietal sources was examined using dynamic
      causal modelling. We found evidence for a systematic change in effective
      connectivity in both diseases. Compared with healthy subjects, who had focal
      modulation of intrahemispheric frontal-temporal connections, the patient groups
      showed abnormally extensive and inefficient networks. The changes in connectivity
      were accompanied by impaired responses of the auditory cortex to unexpected
      deviant tones (MMNm), despite normal responses to standard stimuli. Together,
      these results suggest that neurodegeneration in two distinct clinical syndromes
      with overlapping profiles of prefrontal atrophy, causes a similar pattern of
      reorganisation of large-scale networks. We discuss this network reorganisation in
      the context of other focal brain disorders and the specific vulnerability of
      functional brain networks to neurodegenerative disease.

PMID- 23853764
TI  - Experiences of being a young male Sami reindeer herder: a qualitative study in
      perspective of mental health.
AB  - OBJECTIVES: To explore experiences of what it is to be a young male Sami reindeer
      herder in Sweden, a group with previously known stigma and specific health
      issues, and to understand experiences in perspective of mental health. METHODS: A
      qualitative content analysis was employed. Data were collected by in-depth
      interviews with 15 strategically selected reindeer herders aged 18-35 years old.
      RESULTS: The analysis resulted in 5 sub-themes: (a) being "inside" or "outside"
      is a question of identity; (b) a paradox between being free/bound; (c) an
      experience of various threats and a feeling of powerlessness; (d) specific norms
      for how a "real" reindeer herder should be; and (e) the different impacts and
      meanings of relations. The overarching theme is summarized thus: being a young
      reindeer herder means so many (impossible) dreams and conditions. Overall, the
      experience of the informants was that being a reindeer herder is a privileged
      position that also implies many impossibilities and unjust adversities they have
      no control over, and that there is nothing they can do but "bite the bullet or be
      a failure." CONCLUSIONS: Knowledge about this group's experiences can be used to
      understand difficulties faced by young reindeer herders and its consequences
      regarding mental health problems. This also implies a need for a broader
      perspective when discussing future interventions aimed at preventing mental
      health problems in this group.

PMID- 23853766
TI  - Impact of cardiovascular organ damage on cortical renal perfusion in patients
      with chronic renal failure.
AB  - INTRODUCTION: Properly preserved renal perfusion is the basic determinant of
      oxygenation, vitality, nutrition, and organ function and its structure. Perfusion
      disorders are functional changes and are ahead of the appearance of biochemical
      markers of organ damage. The aim of this study was to evaluate a relationship
      between the renal cortex perfusion and markers of cardiovascular organ damage in
      patients with stable chronic renal failure (CKD). METHODS: Seventeen patients (2
      F; 15 M; age 47 +/- 16) with stable CKD at 2-4 stages and hypertension or signs
      of heart failure were enrolled in this study. Blood tests with an estimation of
      renal and cardiac functions, echocardiographic parameters, intima-media thickness
      (IMT), renal resistance index (RRI), and total (TPI), proximal (PPI), and distal
      (DPI) renal cortical perfusion intensity measurements were collected. RESULTS:
      DPI was significantly lower than PPI. TPI significantly correlated with age, Cys,
      CKD-EPI (cystatin), and IMT, whereas DPI significantly depended on Cystain, CKD
      EPI (cystatin; cystatin-creatinine), IMT, NT-proBNP, and troponin I. In multiple
      stepwise regression analysis model only CKD-EPI (cystatin) independently
      influenced DPI. CONCLUSIONS: Cardiovascular and kidney damage significantly
      influences renal cortical perfusion. Ultrasound measurement of renal perfusion
      could be a sensitive method for early investigation of cardiovascular and renal
      injuries.

PMID- 23853765
TI  - Update on anticytokine treatment for asthma.
AB  - Current advances in the knowledge of asthma pathobiology suggest that
      anticytokine therapies can be potentially useful for the treatment of this
      complex and heterogeneous airway disease. Recent evidence is accumulating in
      support of the efficacy of anti-IL-4, anti-IL-5, and anti-IL-13 drugs. Therefore,
      these new developments are now changing the global scenario of antiasthma
      therapies, especially with regard to more severe disease. Current findings
      referring to variability of individual therapeutic responses highlight that the
      different asthma subtypes need to be well characterized, in order to implement
      phenotype-targeted treatments which in the near future will hopefully be mainly
      based on cytokine-directed biologics. 

PMID- 23853767
TI  - Ventricular dyssynchrony and function improve following catheter ablation of
      nonseptal accessory pathways in children.
AB  - INTRODUCTION: Paradoxical or hypokinetic interventricular septal motion has been
      described in patients with septal or paraseptal accessory pathways. Data
      regarding nonseptal pathways is limited. METHODS AND RESULTS: We quantified left
      ventricular dyssynchrony and function in 16 consecutive children, 14.2 +/- 3.7
      years, weighing 53 +/- 17 kg, prior to and following catheter ablation of
      bidirectional septal (N = 6) and nonseptal (N = 10) accessory pathways. Following
      ablation, the left ventricular ejection fraction increased by 4.9 +/- 2.1% (P =
      0.038) from a baseline value of 57.0% +/- 7.8%. By tissue Doppler imaging, the
      interval between QRS onset and peak systolic velocity (Ts) decreased from a
      median of 33.0 ms to 18.0 ms (P = 0.013). The left ventricular ejection fraction
      increased to a greater extent following catheter ablation of nonseptal (5.9% +/-
      2.6%, P = 0.023) versus septal (2.5% +/- 4.1%, P = 0.461) pathways. The four
      patients with an ejection fraction <50%, two of whom had left lateral pathways,
      improved to >50% after ablation. Similarly, the improvement in dyssynchrony was
      more marked in patients with nonseptal versus septal pathways (difference between
      septal and lateral wall motion delay before and after ablation 20.6 +/- 7.1 ms (P
      = 0.015) versus 1.4 +/- 11.4 ms (P = 0.655)). CONCLUSION: Left ventricular
      systolic function and dyssynchrony improve after ablation of antegrade-conducting
      accessory pathways in children, with more pronounced changes noted for nonseptal
      pathways.

PMID- 23853768
TI  - Neuropsychiatric symptoms of dementia: consent, quality of life, and dignity.
AB  - Degenerative forms of dementia are progressive, incurable, fatal, and likely to
      cause suffering in conjunction with personal incapacity. Timely diagnostic
      disclosure and counseling can facilitate important advance care planning. The
      risk of harm associated with neuropsychiatric symptoms (NPS) of dementia often
      has to be balanced against the risk of harm associated with medication management
      of NPS. A palliative care framework can help preserve autonomy, quality of life,
      comfort, and dignity for patients with NPS. 

PMID- 23853769
TI  - Antioxidant capacity and antimutagenic potential of Murraya koenigii.
AB  - It is well known that the intake of antioxidants with increased consumption of
      fruits and vegetables and medicinal herbs contributes towards reduced risk of
      certain diseases including cancers. This study aims to evaluate the broad
      spectrum antioxidant and antimutagenic activities as well as to elucidate
      phytochemical profile of an Indian medicinal plant Murraya koenigii (curry)
      leaves. Leaves of the plant were successively fractionated in various organic
      solvents. Benzene fraction demonstrated the highest phenolic content followed by
      petroleum ether. The benzene fraction showed maximum antioxidant activity in all
      tested assays, namely, phosphomolybdenum, 2,2-diphenyl-1-picrylhydrazyl (DPPH)
      free radical, ferric reducing antioxidant power (FRAP) and cupric reducing
      antioxidant capacity (CUPRAC) assays. Based on the promising broad-spectrum
      antioxidant activity, benzene fraction was further evaluated for antimutagenic
      activity and showed a dose-dependent antimutagenic response in Ames Salmonella
      mutagenicity assay. It inhibited 72-86% mutagenicity induced by sodium azide,
      methyl methanesulfonate, benzo(a)pyrene, and 2-aminoflourene at the maximum
      tested concentration (100 MUg/mL) in Salmonella typhimurium tester strains. At
      least 21 compounds were detected by GC/MS. The findings clearly demonstrated that
      phenolic-rich benzene fraction has promising broad-spectrum antioxidant and
      antimutagenic property and needs further evaluation to exploit its therapeutic
      potential.

PMID- 23853770
TI  - Identification, selection, and enrichment of cardiomyocyte precursors.
AB  - The large-scale production of cardiomyocytes is a key step in the development of
      cell therapy and tissue engineering to treat cardiovascular diseases,
      particularly those caused by ischemia. The main objective of this study was to
      establish a procedure for the efficient production of cardiomyocytes by
      reprogramming mesenchymal stem cells from adipose tissue. First, lentiviral
      vectors expressing neoR and GFP under the control of promoters expressed
      specifically during cardiomyogenesis were constructed to monitor cell
      reprogramming into precardiomyocytes and to select cells for amplification and
      characterization. Cellular reprogramming was performed using 5'-azacytidine
      followed by electroporation with plasmid pOKS2a, which expressed Oct4, Sox2, and
      Klf4. Under these conditions, GFP expression began only after transfection with
      pOKS2a, and less than 0.015% of cells were GFP(+). These GFP(+) cells were
      selected for G418 resistance to find molecular markers of cardiomyocytes by RT
      PCR and immunocytochemistry. Both genetic and protein markers of cardiomyocytes
      were present in the selected cells, with some variations among them. Cell
      doubling time did not change after selection. Together, these results indicate
      that enrichment with vectors expressing GFP and neoR under cardiomyocyte-specific
      promoters can produce large numbers of cardiomyocyte precursors (CMPs), which can
      then be differentiated terminally for cell therapy and tissue engineering. 

PMID- 23853771
TI  - Reduction of orbital inflammation following decompression for thyroid-related
      orbitopathy.
AB  - PURPOSE: Thyroid-related orbitopathy (TRO) is associated with inflammation,
      expansion of orbital fat, enlargement of extraocular muscles, and optic
      neuropathy (ON). We examined the effects of orbital decompression on the
      inflammatory and congestive signs of TRO in patients who underwent emergent
      orbital decompression. METHODS: This retrospective, consecutive study included
      patients with ON from TRO who underwent orbital decompression. Pre- and
      postoperative orbital inflammatory signs in the operated and nonoperated,
      contralateral eyes were graded with the 10-item clinical activity score (CAS).
      RESULTS: Thirty-one orbits were included. Postoperatively, 22 patients and 29
      orbits had resolution of ON while the remaining 2 patients had improvement in
      visual acuity. Mean preoperative CAS was 9.5 +/- 0.4. At 12 months, postoperative
      CAS was 2.1 +/- 0.6 (P < 0.01) in the operated eye and 3.2 +/- 0.5 (P < 0.05) in
      the nonoperated, contralateral eye. CONCLUSION: In our series, 94% of orbits had
      resolution of ON. There was also a statistically significant postoperative
      reduction in the CAS in both the operated and nonoperated, contralateral eyes.
      This phenomenon may be due to lowered venous congestion, decreased intraorbital
      pressure, and diminution in inflammatory factors.

PMID- 23853772
TI  - Genetic epidemiology, hematological and clinical features of hemoglobinopathies
      in Iran.
AB  - There is large variation in the molecular genetics and clinical features of
      hemoglobinopathies in Iran. Studying structural variants of hemoglobin
      demonstrated that the beta-chain variants of hemoglobin S and D-Punjab are more
      prevalent in the Fars (southwestern Iran) and Kermanshah (western Iran)
      provinces, respectively. Also, alpha-chain variants of Hb Q-Iran and Hb Setif are
      prevalent in western Iran. The molecular basis and clinical severity of
      thalassemias are extremely heterogenous among Iranians due to the presence of
      multiethnic groups in the country. beta-Thalassemia is more prevalent in northern
      and southern Iran. Among 52 different beta-thalassemia mutations that have been
      identified among Iranian populations, IVSII-1 G:A is the most frequent mutation
      in most parts of the country. The presence of IVS I-5 G:C mutation with high
      frequency in southeastern Iran might reflect gene flow from neighboring
      countries. A wide spectrum of alpha-thalassemia alleles has been detected among
      Iranians with -alpha(3.7 kb) as the most prevalent alpha-thalassemia mutation.
      The prevention program of thalassemia birth in Iran has reduced the birth rate of
      homozygous beta-thalassemia since the implementation of the program in 1997. In
      this review genetic epidemiology, clinical and hematological aspects of
      hemoglobinopathies, and the prevention programs of beta-thalassemia in Iran will
      be discussed.

PMID- 23853773
TI  - Mucosal leishmaniasis: an underestimated presentation of a neglected disease.
AB  - We present a review of current knowledge about mucosal leishmaniasis (ML).
      Although involvement of mucous membranes is classically admitted in New World
      leishmaniasis, particularly occurring in infection by Leishmania (L.)
      braziliensis species complex, ML is also a possible presentation of Old World
      leishmaniasis, in either L. donovani or L. major species complex infections.
      Thus, ML has to be considered not only as a Latin American disease but as an Old
      and New World disease. We describe ML epidemiology, pathogenesis, clinics,
      diagnosis, and therapy. Considering both its highly disfiguring lesions and its
      possible lethal outcome, ML should not be underestimated by physicians. Moreover,
      leishmaniasis is expected to increase its burden in many countries as sandfly
      vector distribution is widespreading towards non-endemic areas. Finally, the lack
      of clear understanding of ML pathogenesis and the absence of effective human
      vaccines strongly claim for more research. 

PMID- 23853774
TI  - Comparison of breast cancer-related lymphedema (upper limb swelling) prevalence
      estimated using objective and subjective criteria and relationship with quality
      of life.
AB  - This study aimed to investigate lymphedema prevalence using three different
      measurement/diagnostic criterion combinations and explore the relationship
      between lymphedema and quality of life for each, to provide evaluation of
      rehabilitation. Cross-sectional data from 617 women attending review appointments
      after completing surgery, chemotherapy, and radiotherapy included the Morbidity
      Screening Tool (MST; criterion: yes to lymphedema); Lymphedema and Breast Cancer
      Questionnaire (LBCQ; criterion: yes to heaviness and/or swelling); percentage
      limb volume difference (perometer: %LVD; criterion: 10%+ difference); and the
      Functional Assessment of Cancer Therapy breast cancer-specific quality of life
      tool (FACT B+4). Perometry measurements were conducted in a clinic room. Between
      341 and 577 participants provided sufficient data for each analysis, with mean
      age varying from 60 to 62 (SD 9.95-10.03) and median months after treatment from
      49 to 51. Lymphedema prevalence varied from 26.2% for perometry %LVD to 20.5% for
      the MST and 23.9% for the LBCQ; differences were not significant. Limits of
      agreement analysis between %LVD and the subjective measures showed little
      consistency, while moderate consistency resulted between the subjective measures.
      Quality of life differed significantly for women with and without lymphedema only
      when subjective measurements were used. Results suggest that subjective and
      objective tools investigate different aspects of lymphedema. 

PMID- 23853775
TI  - The role of DPP4 activity in cardiovascular districts: in vivo and in vitro
      evidence.
AB  - The introduction of incretin hormone-based therapies represents a novel
      therapeutic strategy, since these drugs not only improve glycemia with minimal
      risk of hypoglycemia, but also have other extraglycemic beneficial effects. These
      agents, which are effective in improving glucose control, could also have
      positive effects on the incidence of cardiovascular events. The aim of this
      review is to summarize the present literature about the role of dipeptidyl
      peptidase 4 (DPP4) in cardiovascular districts, not only strictly correlated to
      its effect on glucagon-like peptide-1 (GLP-1) circulating levels, but also to
      what is known about possible cardiovascular actions. Actually, DPP4 is known to
      be present in many cells and tissues and its effects go beyond purely metabolic
      aspects. Almost always the inhibition of DPP4 activity is associated with
      improved cardiovascular profile, but it has shown to possess antithrombotic
      properties and these different effects could be connected with a site and/or
      species specificity of DPP4. Certainly, DPP4 seems to exert many functions, both
      directly and indirectly, on cardiovascular districts, opening new possibilities
      of prevention and treatment of complications at this level, not only in patients
      affected by diabetes mellitus. 

PMID- 23853777
TI  - Characterization of new N,O-dialkyl phosphoramidate-bonded stationary phases for
      reversed-phase HPLC - retention and selectivity.
AB  - The chromatographic properties of new N,O-dialkyl phosphoramidate stationary
      phases were studied. Obtained stationary phases containing C10 (Amino-P-C10) and
      C18 alkyl chains (Amino-P-C18) were attached to aminopropyl silica using the
      phosphate group. As basic characteristics of the bonded phases, the
      hydrophobicity and silanol activity (polarity) were investigated. Columns were
      compared according to the methylene selectivities using a series of alkylbenzene
      homologues and according to their shape and size selectivities using polycyclic
      aromatic hydrocarbons (PAHs). The measurements were done using methanol (MeOH)
      water and acetonitrile (ACN)-water mobile phases. The presented results show that
      the coverage density of the bonded ligands and the length of the alkyl chains
      strongly influence the retention and selectivity of the N,O-dialkyl
      phosphoramidate bonded phases in reversed-phase liquid chromatography. The
      presence of the polar amino and phosphoramidate groups in the structure of the
      bonded ligands strongly influence the polarity of the bonded phase. A higher
      hydrophobicity is exhibited by the Amino-P-C18 adsorbent. The chromatographic
      properties of the new stationary phases were compared with octadecyl, cholesterol
      bonded and immobilized artificial membrane (IAM) stationary phases. 

PMID- 23853776
TI  - Antioxidant N-acetylcysteine attenuates the reduction of Brg1 protein expression
      in the myocardium of type 1 diabetic rats.
AB  - Brahma-related gene 1 (Brg1) is a key gene in inducing the expression of
      important endogenous antioxidant enzymes, including heme oxygenase-1 (HO-1) which
      is central to cardioprotection, while cardiac HO-1 expression is reduced in
      diabetes. It is unknown whether or not cardiac Brg1 expression is reduced in
      diabetes. We hypothesize that cardiac Brg1 expression is reduced in diabetes
      which can be restored by antioxidant treatment with N-acetylcysteine (NAC).
      Control (C) and streptozotocin-induced diabetic (D) rats were treated with NAC in
      drinking water or placebo for 4 weeks. Plasma and cardiac free15-F2t-isoprostane
      in diabetic rats were increased, accompanied with increased plasma levels of
      tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6), while cardiac
      Brg1, p-STAT3 and HO-1 protein expression levels were significantly decreased.
      Left ventricle weight/body weight ratio was higher, while the peak velocities of
      early (E) and late (A) flow ratio was lower in diabetic than in C rats. NAC
      normalized tissue and plasma levels of 15-F2t-isoprostane, significantly
      increased cardiac Brg1, HO-1 and p-STAT3 protein expression levels and reduced
      TNF-alpha and IL-6, resulting in improved cardiac function. In conclusion,
      myocardial Brg1 is reduced in diabetes and enhancement of cardiac Brg1 expression
      may represent a novel mechanism whereby NAC confers cardioprotection. 

PMID- 23853778
TI  - A protein nanofiber hydrogel for sensitive immunoassays.
AB  - Amyloid-like protein nanofibers were assembled in vitro using a recombinant
      protein fusion, with yeast Sup35 and human SSB/La proteins as assembly units,
      where the length of the nanofibers was mostly between 100 and 400 nm. The protein
      nanofibers, hereafter referred to as Sup35-based protein nanofiber probes
      (SuPNPs), were used to sensitively detect anti-SSB/La antibodies [Sjogren's
      syndrome (SS)-specific marker]. After, the SuPNPs were vinylated and subsequently
      linked to acrylamide. The polymerization reaction with acrylamide formed a SuPNP
      hydrogel with uniform porosity, where the SuPNPs were directly cross-linked to
      polyacrylamide. Alternatively, biotinylated SuPNPs (bt-SuPNP) were attached to a
      streptavidin-hydrogel, resulting in the formation of a bt-SuPNP-hydrogel. When
      both the SuPNP-hydrogel and bt-SuPNP-hydrogel were used as 3D assay platforms for
      the detection of anti-SSB/La antibodies in a buffer solution, the LODs (limit of
      detection) were found to be 10 pM for both, showing 100-fold enhancement in
      sensitivity compared to conventional 2D polystyrene (PS) plate-based assays. It
      seems that the exposed surface and uniform distribution of the SuPNPs within the
      3D space of the porous hydrogel matrix interacted more effectively with the anti
      SSB/La antibodies, leading to more sensitive detection. The equal sensitivity
      demonstrated by the SuPNP- and bt-SuPNP-hydrogels above indicates that the target
      binding activity of the SuPNPs remains unchanged when either directly cross
      linked to the hydrogel or indirectly immobilized to the hydrogel via
      streptavidin. When used to detect anti-SSB/La antibodies in human serum, the
      SuPNP-hydrogel is 1000 times more sensitive than a 2D PS plate. It seems that non
      specific adsorption of the serum proteins occurs heavily on the 2D PS plate.
      While diagnostic assays for Sjogren's syndrome were demonstrated as proof-of
      concept in this study, the SuPNP-hydrogel can be generally applied for the
      sensitive and specific detection of many other disease markers. 

PMID- 23853779
TI  - Multi-walled carbon nanotubes and metal-organic framework nanocomposites as novel
      hybrid electrode materials for the determination of nano-molar levels of lead in
      a lab-on-valve format.
AB  - Metal-organic frameworks have been the subject of intense research because of
      their unique physicochemical properties. The presented study investigates the
      application of multi-wall carbon nanotubes and metal-organic frameworks
      (MWCNTs@Cu3(BTC)2) nanoparticles-modified electrode for the determination of
      trace levels of lead. The nanocomposites were prepared by solvothermal synthesis
      and characterized in detail. The experimental procedure was carried out by
      accumulating lead on the electrode surface and subsequently measuring with
      differential pulse anodic stripping voltammetry in a lab-on-valve format. The
      main parameters affecting the analytical performance, including the amount of
      MWCNTs@Cu3(BTC)2 suspension, supporting electrolyte and its pH, stripping mode,
      and flow rate, have been investigated in detail. Under the optimum conditions,
      the oxidation peak current displayed a calibration response for lead over a
      concentration range from 1.0 * 10(-9) to 5.0 * 10(-8) mol L(-1) with a excellent
      detection limit of 7.9 * 10(-10) mol L(-1). The relative standard deviation of 7
      successive scans was 3.10% for 1.0 * 10(-8) mol L(-1) lead. The established
      method showed a great improvement in sensitivity and sample throughput for lead
      analysis. 

PMID- 23855009
TI  - Dorsal augmentation with diced cartilage enclosed with temporal fascia in
      secondary endonasal rhinoplasty.
AB  - BACKGROUND: Placement of diced cartilage enclosed within an autologous fascia
      sleeve (DC-F) for nasal dorsum reconstruction is common in open rhinoplasty, but
      there are no data regarding its use in closed rhinoplasty (the endonasal
      approach). OBJECTIVES: The authors describe a technique for augmenting the nasal
      dorsum in secondary rhinoplasty with DC-F grafts via an endonasal approach.
      METHODS: In this study, the authors retrospectively review the cases of 18
      patients who underwent closed rhinoplasty with the authors' technique between
      2008 and 2011. Cartilage harvested from the septum, rib, or concha was diced into
      0.5- to 1-mm cubes. A rectangle of deep temporal fascia (approximately 5 * 5 cm)
      was harvested by means of a single V-shaped incision overlying the temporal
      fossa, then wrapped around another 1-mL syringe and secured. The fascial cylinder
      was filled with the desired amount of diced cartilage and then sutured closed at
      both ends. This graft was placed into the dorsum of the nose via the endonasal
      approach. RESULTS: Average age of the patients was 32 years. The patients were
      followed for a minimum of 15 months. Donor site for cartilage harvest was conchal
      in 8 patients, septal and conchal in 6 cases, and costal in 4. Complications were
      encountered in 3 patients, only 1 of whom required surgical revision for contour
      irregularity. No resorption of cartilage was encountered in any patient after 15
      months. Smooth continuity of the nasal dorsum was achieved in all our patients.
      CONCLUSIONS: Despite the lack of a large volume of patients for overwhelming and
      conclusive results, our study provides further confirmation that this technique
      is indeed an attractive option for nasal dorsum reconstruction.

PMID- 23855010
TI  - Retaining ligaments of the face: review of anatomy and clinical applications.
AB  - The retaining ligaments of the face are important in understanding concepts of
      facial aging and rejuvenation. They are located in constant anatomic locations
      where they separate facial spaces and compartments. Their superficial extensions
      form subcutaneous septa that separate facial fat compartments. Their main
      significance relates to their surgical release in order to achieve the desired
      aesthetic outcome. Furthermore, they have a sentinel role in their anatomic
      relationship to facial nerve branches. When performing facial aesthetic surgery,
      plastic surgeons should select a plane of dissection, release the appropriate
      ligaments depending on the desired aesthetic goals, and avoid nerve injury by
      using the ligaments as anatomic landmarks. Descriptions of the retaining
      ligaments are variable in the literature; due to different interpretations of
      anatomy, several classifications, locations, and nomenclature systems have been
      proposed. This article will review and clarify the anatomy of the retaining
      ligaments of the face, including the cheek, mandible, temporal, and periorbital
      areas. 

PMID- 23855011
TI  - Concurrent elevation of the upper lateral cartilage perichondrium and nasal bone
      periosteum for management of dorsum: the perichondro-periosteal flap.
AB  - A meticulous nasal dorsal dissection is an indispensable tool for a successful
      rhinoplasty. To achieve an aesthetically pleasing dorsum, fine dissection of the
      upper lateral cartilages (ULC), nasal bones, and keystone area is crucial. In
      this Featured Operative Technique article, the author describes a different
      concept of nasal dorsal skeletonization: the perichondro-periosteal flap
      technique. This technique has several advantages in restoring the nasal dorsum
      after hump reduction. Namely, the preparation and protection of the perichondrium
      and the periosteum of the nasal dorsum as a single entity allows a healthier,
      separate-layer closure over the osseocartilaginous dorsum. 

PMID- 23855012
TI  - Young foster children and their carers: an approach to assessing relationships.
AB  - OBJECTIVE: This article outlines an approach to assessing the quality of
      relationships between young foster children and their carers. These children are
      at high risk of disorganised attachment relationships and of developmental
      psychopathology given their relational experiences prior to and in care. During a
      semi-structured play interaction the emphasis is on identifying behaviours of
      clinical interest. This can be complex given the likelihood of atypical or
      unexpected behaviours expressed within relationships. METHOD: The paper draws on
      literature on the clinical application of attachment theory to the assessment of
      relationships and on the authors' experience of developing and delivering an
      assessment and intervention service for children aged 0 to 5-years-old within a
      mental health service for children in foster care. Clinical material is used to
      illustrate and develop the issues. CONCLUSION: The case for including a semi
      structured observational procedure as part of a comprehensive assessment of
      foster children and their carers is outlined. This is argued to have more
      clinical utility than formal approaches to attachment classification. The
      benefits of including a semi-structured and relational approach to clinical
      assessment of foster children are outlined along with the need to be cautious in
      the use of attachment related terminology when formal assessments have not been
      undertaken.

PMID- 23855013
TI  - Parental cognitive appraisals and coping behaviours following child's epilepsy
      diagnosis: a qualitative study.
AB  - Management of childhood epilepsy places significant demands and increased stress
      on the family unit. How parents adjust to this illness-related stress is believed
      to be shaped by their cognitive appraisals of the situation and the coping
      behaviours that are employed (Wallander & Varni, 1992). We investigated the
      cognitive and behavioural strategies that regulated psychological symptomatology
      in mothers following an epilepsy diagnosis of their child. Twenty-one mothers
      participated in this qualitative study. Interview data was analyzed using theory
      driven thematic analysis. The analysis revealed common effective cognitive
      appraisals that include maintaining a positive outlook, re-structuring
      expectations and finding meaning from their experiences. Problem-solving,
      emotional venting, time to self and speaking with parents in similar situations
      were behaviours that buffered against carer strain. The coping strategies
      identified in this study can be seen as sources of resilience and therefore
      provide a guide for improving parent outcomes in the context of pediatric
      illness. Implications for clinical services are discussed in this paper. 

PMID- 23855014
TI  - Therapeutic clowning in paediatric practice.
AB  - Over the past 30 years, there has been much research into the health benefits of
      humour and laughter. Although often viewed very positively, rigorous evaluation
      of the therapeutic effect of clowning is complex. Clowning is a multi-modal
      intervention, which may have an impact on medical conditions, procedures, family
      functioning and health care teams. Clowns help children to adapt to their
      hospital surroundings and can distract from, and demystify, painful or
      frightening procedures through 'doses of fun' to complement traditional clinical
      interventions. This paper provides a review of the paediatric literature and
      reveals studies looking at the effect of clown interventions on various practical
      procedures and individual medical conditions, and the effects of clowning within
      clinical teams. 

PMID- 23855015
TI  - South Asians' cardiac medication adherence.
AB  - AIM: This paper is a report of a narrative review examining the current state of
      knowledge regarding adherence with cardiac medication among South Asian cardiac
      patients. BACKGROUND: South Asians experience higher rates of cardiovascular
      disease than any other ethnic group. South Asians may be less adherent with a
      cardiac medication regimen than Caucasians. The factors contributing to adherence
      are important to discover to assist South Asians to optimize their cardiac
      health. DATA SOURCES: CINAHL, Medline (Ovid), PsychINFO, EMB Reviews-(Cochrane),
      and EMBASE were accessed using the key words: 'South Asian', 'Asia', 'East
      India', 'India', 'Pakistan', 'Bangladesh', 'Sri Lanka', 'medication compliance',
      'medication noncompliance' and 'medication adherence'. English language papers
      published from January 1980 to January 2013 were eligible for inclusion. REVIEW
      METHODS: Abstracts were reviewed for redundancy and eligibility by the primary
      author. Manuscripts were then retrieved and reviewed for eligibility and validity
      by the first and last authors. Content analysis strategies were used for the
      synthesis. RESULTS: Thirteen papers were in the final data set; most were
      conducted in India and Pakistan. Medication side-effects, cost, forgetfulness and
      higher frequency of dosing contributed to non-adherence. South Asian immigrants
      also faced language barriers, which contributed to non-adherence. Knowledge
      regarding the medications prescribed was a factor that increased adherence.
      CONCLUSION: South Asians' non-adherence to cardiac medications is multifaceted.
      How South Asians who newly immigrate to Western countries make decisions
      regarding their cardiac medication adherence ought to be explored in greater
      detail.

PMID- 23855016
TI  - Iron deficiency anemia screening: a pilot study reexamining a common practice.

PMID- 23855017
TI  - The influence of community context on how coalitions achieve HIV-preventive
      structural change.
AB  - Community coalition action theory (CCAT) depicts the processes and factors that
      affect coalition formation, maintenance, institutionalization, actions, and
      outcomes. CCAT proposes that community context affects coalitions at every phase
      of development and operation. We analyzed data from 12 Connect to Protect
      coalitions using inductive content analysis to examine how contextual factors
      (e.g., economics, collaboration, history, norms, and politics) enhance or impede
      coalitions' success in achieving outcomes. Consistent with CCAT, context affected
      the objectives that coalitions developed and those they completed. Results
      suggest that local prevention history and political support have particular
      impact on coalitions' success in creating structural changes. These data
      underscore the heuristic value of CCAT, yet also imply that the contextual
      constructs that affect outcomes are issue specific. 

PMID- 23855018
TI  - Comparison of a mindful eating intervention to a diabetes self-management
      intervention among adults with type 2 diabetes: a randomized controlled trial.
AB  - Mindful eating may be an effective intervention for increasing awareness of
      hunger and satiety cues, improving eating regulation and dietary patterns,
      reducing symptoms of depression and anxiety, and promoting weight loss. Diabetes
      self-management education (DSME), which addresses knowledge, self-efficacy, and
      outcome expectations for improving food choices, also may be an effective
      intervention for diabetes self-care. Yet few studies have compared the impact of
      mindful eating to a DSME-based treatment approach on patient outcomes. Adults 35
      to 65 years old with type 2 diabetes for >=1 year not requiring insulin therapy
      were recruited from the community and randomly assigned to treatment group. The
      impact of a group-based 3-month mindful eating intervention (MB-EAT-D; n = 27) to
      a group-based 3-month DSME "Smart Choices" (SC) intervention (n = 25)
      postintervention and at 3-month follow-up was evaluated. Repeated-measures ANOVA
      with contrast analysis compared change in outcomes across time. There was no
      significant difference between groups in weight change. Significant improvement
      in depressive symptoms, outcome expectations, nutrition and eating-related self
      efficacy, and cognitive control and disinhibition of control regarding eating
      behaviors occurred for both groups (all p < .0125) at 3-month follow-up. The SC
      group had greater increase in nutrition knowledge and self-efficacy than the MB
      EAT-D group (all p < .05) at 3-month follow-up. MB-EAT-D had significant increase
      in mindfulness, whereas the SC group had significant increase in fruit and
      vegetable consumption at study end (all p < .0125). Both SC and MB-EAT-D were
      effective treatments for diabetes self-management. The availability of mindful
      eating and DSME-based approaches offers patients greater choices in meeting their
      self-care needs. 

PMID- 23855019
TI  - Tough choices in tough times: debt and medication nonadherence.
AB  - Debt is a ubiquitous component of households' financial portfolios. Yet we have
      scant understanding of how household debt constrains spending on needed health
      care. Diverse types of debt have different financial properties and recent work
      has shown that they may have varying implications for spending on needed health
      care. In this article, we explore the associations between indebtedness and
      medication nonadherence. First, we consider overall debt levels and then we
      disaggregate debt into types. We use a population-based sample of 434 residents
      of southeast Michigan who had been prescribed medications, collected in 2009
      2010, the wake of the Great Recession. We find no association between medication
      nonadherence and total indebtedness. However, when we assess each type of debt
      separately, we find that having medical or credit card debt is positively
      associated with medication nonadherence, even net of household income, net worth,
      and other characteristics. Furthermore, patients with greater amounts of medical
      or credit card debt are more likely to be nonadherent than those with less. Our
      results suggest that credit card debt and medical debt may have serious
      implications for the relative affordability of prescription medications. These
      associations have been overlooked in past research and deserve further
      examination. 

PMID- 23855020
TI  - Healthy gardens/healthy lives: Navajo perceptions of growing food locally to
      prevent diabetes and cancer.
AB  - Poor access to nutritious foods, departure from traditional diets, and reduced
      physical activity are associated with a rise in type 2 diabetes and certain types
      of cancers among the Navajo. Diabetes in particular is of concern because of its
      increased prevalence among Navajo youth. Gardening can successfully address
      issues of poor availability of fruits and vegetables and offer many other social
      and health benefits. Our assessment aimed to determine Navajo attitudes about
      gardening and health in San Juan County, New Mexico. We conducted seven focus
      groups (including 31 people) to assess knowledge and attitudes related to
      gardening and uncover barriers and facilitators to participation in a garden
      project. Each group session was moderated by two Navajo students. Transcripts
      revealed that many Navajo are aware of adverse health issues that occur on the
      reservation, predominantly obesity and diabetes. Participants expressed a
      preference for educational approaches that incorporated cultural traditions,
      respect for elders, use of visual aids, and experiential learning. Several social
      and agronomic barriers to gardening were also mentioned. Results suggested a
      broad interest in promoting gardening especially to reduce the risk of diabetes
      with the added value of enhancing social capital in Navajo communities. 

PMID- 23855021
TI  - Mucinous Cystadenoma in the Upper Lip: Report of Two Cases.
AB  - Mucinous cystadenoma of the salivary gland is a very rare disease, and only a few
      cases have been reported. We report here 2 cases of mucinous cystadenoma in the
      upper lip. The first case was a 57-year-old man and the second was a 42-year-old
      woman. The tumors were painless nodules with a smooth-surfaced mucosa, and
      surgical excisions were performed. Histologically, the tumors were surrounded by
      a fibrous capsule and were composed of multiple cysts lined with columnar
      epithelial cells. The tumor cells contain mucous substances that reacted with
      periodic acid-Schiff base and Alcian blue. Immunohistochemical staining revealed
      that the tumor cells expressed cytokeratin (AE1/3 and CK7), but their
      immunoreactivity with MIB-1 (Ki-67) was less than 3%. They had negative
      immunoreactivity for neuroectoderm markers, S-100 protein, and myoepithelial
      markers, p63, alpha-smooth muscle actin, and calponin, except for the
      accompanying myoepithelial-like cells. No recurrences were noted after surgery at
      7 years and 1 year, respectively. 

PMID- 23855022
TI  - Context is everything: an unusual breast core biopsy case.
AB  - Changes in breast tissue in female-to-male transsexuals following gender
      reassignment and androgen therapy can cause difficulties in interpreting breast
      core biopsies. Clinical history and awareness of histological changes in breast
      tissue associated with androgen treatment are important in such cases. Specimen
      mislabeling is a potential pitfall to be borne in mind while evaluating unusual
      presentations in breast core biopsies. We report a case of a 58-year-old male
      with a well-defined supra areolar lesion clinically thought to be a fibroadenoma.

PMID- 23855023
TI  - Amelanotic adenoma.

PMID- 23855024
TI  - Untold stories of infant loss: the importance of contact with the baby for
      bereaved parents.
AB  - This article presents secondary analysis of data from parents who, 50 to 70 years
      ago, birthed stillborn babies or babies with lethal anomalies and from adult
      children born after these losses. The stories reflect a time in history when
      parents were "protected" from seeing or holding their babies and mothers were
      unable to attend the funeral. There was no understanding by society or caregivers
      for parents' need to process the loss or resources to build memories. They
      provide a strong argument for health care providers to offer such resources to
      parents today and offer grief support. 

PMID- 23855025
TI  - Colleen's story: reflections on the concept of "patient and family centered
      care".
AB  - As a patient who has also been a family caregiver, I would like to offer my
      reflections on the concept of "patient and family centered care." How is it
      defined from a patient perspective? Why is it important? In what circumstances is
      it evident? And where is it lacking? I would like to leave the reader with a list
      of relatively small but, in my experience, powerful things that health care
      workers can do today to improve the patient and family experience. 

PMID- 23855026
TI  - Neighborhood context and breastfeeding behaviors among urban mothers.
AB  - BACKGROUND: Research consistently shows that breastfeeding behaviors vary
      according to individual-level sociodemographic characteristics, yet few studies
      examine contextual variations in breastfeeding. OBJECTIVE: The purpose of this
      study is to examine the association between neighborhood context and
      breastfeeding among a sample of predominately unmarried urban mothers, a group
      with relatively low rates of breastfeeding. METHODS: This study combines census
      tract information with data from 2 waves of the Fragile Families and Child
      Wellbeing Study (n = 4228) to predict the odds of initiating and sustaining
      breastfeeding. RESULTS: Findings indicate that neighborhood socioeconomic
      composition, rather than racial or ethnic concentration, is associated with
      breastfeeding behaviors. More specifically, living in a highly educated
      neighborhood is associated with higher odds of initiating and sustaining
      breastfeeding. CONCLUSION: These results suggest that the breastfeeding behaviors
      of urban mothers vary according to neighborhood educational context.
      Understanding how breastfeeding behaviors are shaped by one's neighborhood
      environment will allow public health initiatives to more effectively target
      vulnerable populations.

PMID- 23855027
TI  - "Lost milk?": Counting the economic value of breast milk in gross domestic
      product.
AB  - BACKGROUND: The contribution of breastfeeding and mothers milk to the economy is
      invisible in economic statistics. OBJECTIVE: This article demonstrates how the
      economic value of human milk production can be included in economic statistics
      such as gross domestic product (GDP) and provides estimates for Australia, the
      United States, and Norway. METHODS: The contribution of human milk and lactation
      to GDP in these countries is estimated using United Nations (System of National
      Accounting) guidelines and conventional economic valuation approaches to
      measuring production in GDP. RESULTS: In Australia, current human milk production
      levels exceed $3 billion annually. The United States has the potential to produce
      human milk worth more than US$110 billion a year, but currently nearly two thirds
      of this value is lost due to premature weaning. In Norway, production valued at
      US$907 million annually is 60% of its potential value. CONCLUSIONS: The potential
      loss of economic value from not protecting women's lactation and milk production
      from competing market pressures is large. Failure to account for mothers' milk
      production in GDP and other economic data has important consequences for public
      policy. The invisibility of human milk reduces the perceived importance of
      programs and regulations that protect and support women to breastfeed. The value
      of human milk can be measured using accepted international guidelines for
      calculating national income and production. It is quantitatively nontrivial and
      should be counted in GDP.

PMID- 23855028
TI  - Stepping up the baby-friendly NICU.

PMID- 23855029
TI  - Lack of knowledge persists about early breastfeeding competence in preterm
      infants.

PMID- 23855030
TI  - International perspectives on donor milk in and beyond the NICU.

PMID- 23855031
TI  - Human milk dose in the first month is inversely associated with sepsis and NICU
      costs.

PMID- 23855033
TI  - What is human donor milk and why might my baby need it?

PMID- 23855032
TI  - Container type and bactericidal activity of human milk during refrigerated
      storage.
AB  - BACKGROUND: Refrigeration of human milk has been recommended for its short-term
      storage. It has been shown that some nutritional, immunological, and bioactive
      properties and bactericidal activity of human milk can be altered during
      refrigeration. Pyrex bottles and polyethylene bags are 2 commonly used containers
      for human milk storage. OBJECTIVE: The aim of this study was to compare the
      association between storage container type on the bactericidal activity of human
      milk for different durations of refrigeration (fresh, and at 24 and 48 hours).
      METHODS: Forty-four samples of human milk were collected from 22 lactating
      mothers. Two samples of breast milk (approximately 10 mL each) were obtained by
      manual expression from each mother. One was collected directly into sterile Pyrex
      bottles and the other into polyethylene bags. One mL of human milk from each
      container was processed immediately after arrival to the laboratory. The
      remaining human milk was kept in the Pyrex and polyethylene containers at 4
      degrees C until analysis at 24 and 48 hours. The bactericidal activity of each
      sample was studied. A strain of Escherichia coli ATCC 25922 was used to determine
      the bactericidal effect of human milk. RESULTS: Bactericidal activity was
      significantly reduced in milk samples stored in polyethylene bags compared to
      those stored in Pyrex bottles when milk samples were stored at 4 degrees C for 24
      and 48 hours (P < .05). CONCLUSION: Short-term storage of human milk in Pyrex
      bottles is more appropriate than polyethylene bags for preserving its
      bactericidal activity against E coli.

PMID- 23855034
TI  - Diagnosing ankyloglossia.

PMID- 23855037
TI  - Flexor tendon injuries in the child.
AB  - This review aims to highlight the differences in the management of flexor tendon
      injuries between children and adults. These include differences in epidemiology,
      anatomy, classification, diagnosis, incisions and skin closure, the size of the
      flexor tendons, technical aspects of zones I and II repairs, core suture purchase
      length, rehabilitation, results, and complications of primary flexor tendon
      repair. Finally, one- versus two-stage flexor tendon reconstruction in children
      is reviewed. 

PMID- 23855038
TI  - Pathological fracture of the trapezoid secondary to an intraosseous ganglion.

PMID- 23855039
TI  - Evaluation of the scratch collapse test for the diagnosis of carpal tunnel
      syndrome.
AB  - This prospective study measured and compared the diagnostic performance
      characteristics of various clinical signs and physical examination manoeuvres for
      carpal tunnel syndrome (CTS), including the scratch collapse test. Eighty-eight
      adult patients that were prescribed electrophysiological testing to diagnose CTS
      were enrolled in the study. Attending surgeons documented symptoms and results of
      standard clinical manoeuvres. The scratch collapse test had a sensitivity of 31%,
      which was significantly lower than the sensitivity of Phalen's test (67%),
      Durkan's test (77%), Tinel's test (43%), CTS-6 lax (88%), and CTS-6 stringent
      (54%). The scratch test had a specificity of 61%, which was significantly lower
      than the specificity of thenar atrophy (96%) and significantly higher than the
      specificity of Durkan's test (18%) and CTS-6 lax (13%). The sensitivity of the
      scratch collapse test was not superior to other clinical signs and physical
      examination manoeuvers for CTS, and the specificity of the scratch collapse test
      was superior to that of Durkan's test and CTS-6 lax. Further studies should seek
      to limit the influence of a patient's clinical presentation on scratch test
      performance and assess the scratch test's inter-rater reliability. 

PMID- 23855041
TI  - New understanding of little-known hip syndrome opens path to pain relief.  Like a
      rotator cuff tear, but in the hip.  Minimally invasive therapy has most patients
      walking without pain in 6-12 weeks.

PMID- 23855040
TI  - The effect of the pressure-volume curve for positive end-expiratory pressure
      titration on clinical outcomes in acute respiratory distress syndrome: a
      systematic review.
AB  - PURPOSE: Methods to optimize positive end-expiratory pressure (PEEP) in acute
      respiratory distress syndrome (ARDS) remain controversial despite decades of
      research. The pressure-volume curve (PVC), a graphical ventilator relationship,
      has been proposed for prescription of PEEP in ARDS. Whether the use of PVC's
      improves survival remains unclear. METHODS: In this systematic review, we
      assessed randomized controlled trials (RCTs) comparing PVC-guided treatment with
      conventional PEEP management on survival in ARDS based on the search of the
      National Library of Medicine from January 1, 1960, to January 1, 2010, and the
      Cochrane Central Register of Controlled Trials. Three RCTs were identified with a
      total of 185 patients, 97 with PVC-guided treatment and 88 with conventional PEEP
      management. RESULTS: The PVC-guided PEEP was associated with an increased
      probability of 28-day or hospital survival (odds ratio [OR] 2.7, 95% confidence
      interval [CI] 1.5, 4.9) using a random-effects model without significant
      heterogeneity (I (2) test: P = .75). The PVC-guided ventilator support was
      associated with reduced cumulative risk of mortality (-0.24 (95% CI -0.38, 
      0.11). The PVC-managed patients received greater PEEP (standardized mean
      difference [SMD] 5.7 cm H2O, 95% CI 2.4, 9.0) and lower plateau pressures (SMD 
      1.2 cm H2O, 95% CI -2.2, -0.2), albeit with greater hypercapnia with increased
      arterial pCO2 (SMD 8 mm Hg, 95% CI 2, 14). Weight-adjusted tidal volumes were
      significantly lower in PVC-guided than conventional ventilator management (SMD
      2.6 mL/kg, 95% CI -3.3, -2.0). CONCLUSION: This analysis supports an association
      that ventilator management guided by the PVC for PEEP management may augment
      survival in ARDS. Nonetheless, only 3 randomized trials have addressed the
      question, and the total number of patients remains low. Further outcomes studies
      appear required for the validation of this methodology.

PMID- 23855042
TI  - Four new studies show advances against prostate cancer.  Men facing prostate
      cancer can now make more informed decisions regarding diagnosis, treatment, and
      quality of life.

PMID- 23855043
TI  - Obesity facts and fiction.  Forget most of the weight loss/gain beliefs you
      probably grew up with; many, it turns out, are unsupported by scientific
      evidence.

PMID- 23855044
TI  - Gateway to brain's memory system.  Stimulating the entorhinal cortex may be a
      mechanism in combating Alzheimer's disease.

PMID- 23855046
TI  - I suffer from vertigo, and a friend recently told me that I might find relief
      with something called the Epley maneuver.  Can you tell me what this is and how
      it works?

PMID- 23855045
TI  - New warnings about atrial fibrillation.  The arrhythmia may be even deadlier than
      previously thought.

PMID- 23855047
TI  - My 30-year-old son recently suffered severe chest pain, causing him to go to the
      emergency room.  He was diagnosed with pericarditis.  What is this, and what
      causes the symptoms?

PMID- 23855048
TI  - I'm very prone to sinus infections, particularly at this time of year with all
      the pollen flying around. What can I do to prevent or manage sinus infections? I
      would like to avoid taking antibiotics.

PMID- 23855049
TI  - Treatment. Least virological failure in children taking efavirenz.

PMID- 23855050
TI  - Testing.  Task force recommends everyone aged 15 to 65 be tested for HIV.

PMID- 23855051
TI  - Prevention. Microbes may be key to why circumcision reduces HIV risk.

PMID- 23855052
TI  - Breastfeeding lowers HIV count in milk.

PMID- 23855053
TI  - Court affirms 7 count criminal HIV transmission conviction.

PMID- 23855054
TI  - Retaliation.  Man with HIV fails to show termination was discriminatory.

PMID- 23855055
TI  - ADA. Jury incorrectly considered disability in decision, court said.

PMID- 23855056
TI  - SSI.  ALJ did not err in finding that man with HIV was not disabled.

PMID- 23855057
TI  - Medicaid and Children's Health Insurance Programs: essential health benefits in
      alternative benefit plans, eligibility notices, fair hearing and appeal
      processes, and premiums and cost sharing; exchanges: eligibility and enrollment.
      Final rule.
AB  - This final rule implements provisions of the Patient Protection and Affordable
      Care Act and the Health Care and Education Reconciliation Act of 2010
      (collectively referred to as the Affordable Care Act. This final rule finalizes
      new Medicaid eligibility provisions; finalizes changes related to electronic
      Medicaid and the Children's Health Insurance Program (CHIP) eligibility notices
      and delegation of appeals; modernizes and streamlines existing Medicaid
      eligibility rules; revises CHIP rules relating to the substitution of coverage to
      improve the coordination of CHIP coverage with other coverage; and amends
      requirements for benchmark and benchmark-equivalent benefit packages consistent
      with sections 1937 of the Social Security Act (which we refer to as ''alternative
      benefit plans'') to ensure that these benefit packages include essential health
      benefits and meet certain other minimum standards. This rule also implements
      specific provisions including those related to authorized representatives,
      notices, and verification of eligibility for qualifying coverage in an eligible
      employer-sponsored plan for Affordable Insurance Exchanges. This rule also
      updates and simplifies the complex Medicaid premium and cost sharing
      requirements, to promote the most effective use of services, and to assist states
      in identifying cost sharing flexibilities. It includes transition policies for
      2014 as applicable.

PMID- 23855058
TI  - Analysis of high-affinity assembly for AMPA receptor amino-terminal domains.

PMID- 23855059
TI  - 2013 Frechette Awards.

PMID- 23855060
TI  - Probability of hypobaric decompression sickness including extreme exposures.
AB  - INTRODUCTION: The fitting of probabilistic decompression sickness (DCS) models is
      more effective when data encompass a wide range of DCS incidence. We obtained
      such data from the Air Force Research Laboratory Altitude Decompression Sickness
      Research Database. The data are results from 29 tests comprising 708 human
      altitude chamber exposures (536 men and 172 women). There were 340 DCS outcomes
      with per-test DCS incidence ranging from 0 to 88%. The tests were characterized
      by direct ascent at a rate of 5000 ft x min(-1) (1524 m x min(-1)) to a range of
      altitudes (226 to 378 mmHg) for 4 h after prebreathe times of varying length and
      with varying degrees of physical activity while at altitude. METHODS: Logistic
      regression was used to develop an expression for the probability of DCS [P(DCS)]
      using the Hill equation with decompression dose as the main predictor. Here,
      decompression dose is defined in terms of either the tissue ratio (TR) or a
      bubble growth index (BGI). Other predictors in the model were gender and peak
      exercise intensity at altitude. RESULTS: All three predictors (decompression
      dose, gender, and exercise intensity) were important contributions to the model
      for P(DCS). DISCUSSION: Higher TR or BGI, male gender, and higher exercise
      intensity at altitude all increased the modeled decompression dose. Using either
      TR or BGI to define decompression dose provided comparable results, suggesting
      that a simple TR is adequate for simple altitude exposures as an abstraction of
      the true decompression dose. The model is primarily heuristic and limits
      estimates of P(DCS) to only a 4-h exposure.

PMID- 23855061
TI  - Amino acid infusion alters the expression of growth-related genes in multiple
      skeletal muscles.
AB  - BACKGROUND: Exercise and nutritional interventions have been examined
      independently as countermeasures to offset the loss of skeletal muscle mass with
      unloading, yet a protocol to completely preserve the soleus has not been
      identified. Little is known regarding the combined effect of exercise and
      nutrition on factors regulating skeletal muscle growth. The purpose of this
      investigation was to evaluate the influence of amino acid (AA) infusion on
      myogenic (MRF-4, MyoD, and Myogenin), proteolytic (MuRF-1, Atrogin-1, FOXO3A,
      Calpain-1, Calpain-2, Caspase-3, Cathepsin L1), and cytokine (IL-6, IL-8, and IL
      15) mRNA transcripts in two skeletal muscles that respond distinctly to
      microgravity unloading. METHODS: Muscle biopsies were obtained from the vastus
      lateralis (VL) and soleus of eight male subjects prior to and after 4 h of AA
      infusion for analysis of mRNA expression. All subjects performed a standardized
      exercise bout (45-min treadmill run) 24 h prior to the AA infusion. RESULTS: In
      the VL, proteolytic factors MuRF-1 and FOXO3A were reduced (44 +/- 9 and 28 +/-
      6%, respectively) in response toAA infusion. In the soleus, mRNA transcripts of
      myogenic factor MRF-4 (91 +/- 36%) and cytokines IL-6, IL-8, and IL-15 were
      elevated while the proteolytic marker FOXO3A mRNA was reduced by 19 +/- 9%.
      DISCUSSION: These data suggest that the expression of genes related to skeletal
      muscle remodeling is altered during acute AA infusion 24 h post-exercise. It
      appears that increased amino acid availability in concert with exercise may
      create an intramuscular environment favorable for the prevention of muscle
      atrophy associated with unloading, which may be particularly beneficial for the
      soleus.

PMID- 23855062
TI  - Threshold altitude for bubble decay and stabilization in rat adipose tissue at
      hypobaric exposures.
AB  - INTRODUCTION: Bubble formation during altitude exposures, causing altitude
      decompression sickness (aDCS), has been referred to in theoretical models as
      venous gas embolisms (VGE). This has also been demonstrated by intravascular gas
      formation. Previous reports indicate that the formation of VGE and aDCS incidence
      increase abruptly for exposures exceeding 40-44 kPa ambient pressures. Further,
      extravascular micro air bubbles injected into adipose tissue grow transiently,
      then shrink and disappear while breathing oxygen (F1O2 = 1.0) at 71 kPa. At 25
      kPa similar air bubbles will grow and stabilize during oxygen breathing without
      disappearing. We hypothesize that an ambient pressure threshold for either
      extravascular bubble stabilization or disappearance may be identified between 71
      and 25 kPa. Whether extravascular bubbles will stabilize above a certain
      threshold has not been demonstrated before. METHODS: In anesthetized rats, micro
      air bubbles (containing 79% nitrogen) of 500 nl were injected into exposed
      abdominal adipose tissue. Rats were decompressed in 2-35 min to either 60, 47, or
      36 kPa and bubbles studied for 215 min during continued oxygen breathing (F1O2 =
      1). RESULTS: Significantly more bubbles shrank and disappeared at 60 (14 of 17)
      and 47 kPa (14 of 15) as compared to bubbles exposed to 36 kPa (3 of 15) ambient
      pressure. CONCLUSION: The results indicate that a threshold causing extravascular
      bubble stabilization or decay is between 47 to 36 kPa. The results are in
      agreement with previous reports demonstrating an increase in the formation of VGE
      and symptoms of aDCS at altitudes higher than 44 kPa ambient pressure.

PMID- 23855063
TI  - Subjective and objective measures of relaxed +Gz tolerance following repeated +Gz
      exposure.
AB  - BACKGROUND: Repeated exposure to +Gz acceleration provokes cardiovascular
      adaptations of potential benefit to pilots' +Gz tolerance, but whether such
      changes actually improve human tolerance to +Gz acceleration is uncertain. This
      study assessed +Gz tolerance before and after repeated exposure to +Gz at two
      different intensities as the role of frequency of +Gz exposure in adaptation also
      remains unknown. METHODS: In a cross-over design, 10 experienced male centrifuge
      volunteers completed two experimental conditions separated by at least 3 wk.
      Subjects completed four simulated air combat maneuvers (SACM) on a human
      centrifuge, either twice or four times per week, for 3 consecutive weeks. Relaxed
      +Gz tolerance (RGT) during a gradual onset run (GOR, 0.1 G x s(-1)) and
      cardiovascular responses to rapid and incremental head-up tilt were assessed
      before and after each condition. RESULTS: Rapid and incremental head-up tilt
      increased both mean arterial and diastolic blood pressures following +Gz
      exposure. +Gz exposure attenuated the increase in heart rate (+9 +/- 3 vs. +11 +/
      3 mmHg/Gz) and the decrease in eye-level systolic blood pressure (-11 +/- 3 vs. 
      14 +/- 4 mmHg/Gz) during GOR, but had no effect on RGT (4/wk: +3.88 +/- 0.56 vs.
      +3.92 +/- 0.63 Gz; 2/wk: +3.89 +/- 0.69 vs. +3.92 +/- 0.69 Gz). DISCUSSION:
      Frequent +Gz acceleration, either as 2 (8 SACMs) or 4 sessions (16 SACMs) per
      week for 3 wk, enhances cardiovascular tolerance to orthostatic stress but does
      not improve RGT measured during a GOR.

PMID- 23855064
TI  - A novel method to detect heat illness under severe conditions by monitoring
      tympanic temperature.
AB  - INTRODUCTION: We report a new methodology for detecting heat illness based on
      continuous tympanic temperature monitoring. This is relevant to industrial
      workers, astronauts, and pilots, as well as athletes. Here we evaluate the method
      in Grand Touring (GT) car racers in the closed-cockpit category who can face life
      threatening hyperthermia. METHODS: The system comprises an earpiece containing an
      infrared-radiation-type tympanic thermometer and a microspeaker. In 10 healthy
      subjects, using a temperature-controlled water bath in the laboratory, we
      determined the differences in measurements taken from an infrared thermometer in
      one ear canal and from a thermistor probe in the other ear canal for direct
      tympanic temperature measurement. We employed an ingestible telemetry pill for
      gastrointestinal temperature measurement as a reference of core temperature. Then
      we assessed the usefulness of the system under real racing conditions with two
      professional drivers in the 2010 Super GT International Series held at the Twin
      Ring Motegi in Japan. RESULTS: The results showed a good correlation between the
      infrared tympanic temperature and both the direct one (r = 0.985) and the
      gastrointestinal temperature (r = 0.932). The mean difference between these
      temperatures was +0.01 degree C and +0.27 degrees C, with 95% confidence
      intervals (equal to 1.96 SD) of 0.30 degrees C and 0.58 degrees C, respectively.
      As for the field test, the system functioned well during real competitive and
      extremely severe race conditions on the racing circuit. CONCLUSIONS: The new
      method was found to perform well in an extreme car racing setting. It has the
      potential to be used in other applications, including the industrial and
      aerospace sectors.

PMID- 23855065
TI  - Subjective ratings and performance in the heat and after sleep deprivation.
AB  - BACKGROUND: It has been shown that endurance performance after one night of sleep
      deprivation is not compromised despite the feeling of fatigue and that, in
      contrast, performance in the heat deteriorates even though people may feel good.
      However, it is essentially unknown how the estimation of performance capabilities
      relate to actual performance. We hypothesized that endurance performance in the
      heat would be overestimated and performance after sleep deprivation would be
      underestimated. We also hypothesized that jumping performance will be
      underestimated in the heat. METHODS: There were 11 fit (VO2peak 52.0 +/- 3.7 ml x
      kg(-1) x min(-1)) men, familiar with cycling, who performed a 20-min all-out
      cycling test (AO) and a vertical jump test (VJ) under four different conditions:
      a test trial at 24 degrees C, at 11 degrees C ambient temperature without (C) and
      with one night of sleep deprivation (CS), and at 31 degrees C (H). The subjects
      estimated the performance prior to exercise in CS, C, and H. RESULTS: AO
      performance was less for H (6.95 +/- 0.36 km) than for C (7.68 +/- 0.29 km) and
      CS (7.62 +/- 0.33 km). The subjects underestimated AO performance for CS by 1.11
      km and C by 0.42 kmin, but not for H. VJ was higher in the H condition, in
      contrast with subjects' assessment. DISCUSSION: We conclude that subjective
      estimates of performance are not in line with actual performance for endurance
      exercise after sleep deprivation and for explosive exercise in the heat.

PMID- 23855066
TI  - Escape from a submersible vehicle simulator wearing different thermoprotective
      flotation clothing.
AB  - BACKGROUND: Winter road workers, who drive heavy vehicles on ice-covered
      waterways, are at risk for ice failure and subsequent drowning in frigid water.
      Some workers who are recommended to wear thermoprotective flotation clothing are
      concerned that buoyancy or bulk may impede underwater exit. METHODS: Using a
      simulator, 10 volunteers (2 women) compared everyday winter clothing (Control), a
      flotation Jacket and Overall, and an inflated inflatable personal flotation
      device (Inflated Vest). On each study day, all clothing conditions were tested in
      either Cool (20 degrees C) or Cold (8 degrees C) water conditions using a
      randomized balance design. After each trial, subjective ratings for thermal
      sensation and exit tasks along with exit task times were determined. RESULTS:
      Exit task times were unaffected by clothing or water conditions. Compared to
      Control, the Inflated Vest was rated with higher exit task difficulty and
      impedance, while the Jacket and Overall were not (ratings for exit task
      difficulty and impedance in cold water were: Control, 'a little' and 'none';
      Jacket, 'a little' and 'a little'; Overall, 'a little' and 'moderate'; and
      Inflated Vest, 'moderate' and 'moderate - a lot'). Finally, there was a training
      effect, with total exit times improving by 20% from trials 1-8 (12.3 to 9.8 s).
      CONCLUSIONS: Results suggest that, compared to Control clothing, flotation
      Jackets and Overalls do not increase exit time or impede exit during egress from
      a submerged vehicle while providing thermoprotection and buoyancy in 20 degrees C
      and 8 degrees C water. The Inflated Vest created the most perceived exit
      impedance in comparison to Control.

PMID- 23855067
TI  - Space motion sickness and motion sickness: symptoms and etiology.
AB  - The adverse symptoms of space motion sickness (SMS) have remained problematic
      since the beginning of manned spaceflight. Despite over 50 yr of research SMS
      remains a problem that affects about half of all space travelers during the first
      24-72 h of a spaceflight. SMS has been treated as another form of motion sickness
      (MS) despite distinct differences in symptomology. In this review SMS and MS
      differences are examined and documented based on available data. Vestibular
      biomechanics that occur during weightlessness coupled with theoretical assertions
      regarding human evolution have led us to propose a two-component model of SMS.
      The first component involves conflicting sensory signals inherent to the otolith
      organs that occur during weightlessness. The second component is a bimodal
      conflict between the otoliths and semicircular canals that can occur during
      normal head movements in weightlessness. Both components may inadvertently, and
      mistakenly, signal that a vestibular malfunction has occurred, hence initiating a
      protective mechanism that may produce symptoms that discourage activity.

PMID- 23855068
TI  - Autonomic nervous system modulation during accidental syncope induced by heat and
      orthostatic stress.
AB  - BACKGROUND: Heart rate variability (HRV) indices (LF, HF, LF/HF, RMSSD, and
      pNN50) under combined heat and orthostatic stress leading up to and during
      accidental syncope (EXP group: one man, two women; age: 23.7 +/- 2.9 yr) were
      compared with data collected from subjects who did not experience syncope (CON
      group: one man, two women; age: 22.3 +/- 1.5 yr). METHODS: Minute averages of HRV
      indices were collected during 5 min at baseline (Base), 5 min leading up to
      syncope (PRE), and 5 min during syncope (Syncope) (i.e., 2 min leading up to, 1
      min during, and 2 min post-syncope). Data were individually analyzed as 1-min
      means during Syncope as well as 5-min means during Base, PRE, and Syncope.
      RESULTS: Between-group results revealed that LF and LF/HF were significantly
      higher and HF was significantly lower in EXP compared to CON subjects at minutes
      1, 2, and 3 during Syncope. Further, RMSSD (CON: 161.1 +/- 37.0 ms; EXP: 17.5 +/-
      13.3 ms) and pNN50 (CON: 26.4 +/- 36.3%; EXP: 1.3 +/- 1.2%) were significantly
      lower in EXP compared to CON subjects at minute 3 during Syncope. During Syncope,
      5-min averages of LF (CON: 46.1 +/- 13.9 nu; EXP: 77.5 +/- 6.6 nu) and LF/HF
      (CON: 1.0 0.5; EXP: 3.8 +/- 1.7) were significantly higher, and HF (CON: 53.9 +/-
      13.9 nu; EXP: 22.5 +/ 1 6.6 nu) was significantly lower in EXP subjects compared
      to CON. DISCUSSION: Our findings show that autonomic nervous system modulation
      leading up to and during accidental syncope induced by heat and orthostatic
      stress is characterized by an exaggerated suppression of parasympathetic and
      elevation of sympathetic activity. Thus, elevated LF and LF/HF, and lower HF,
      RMSSD, and pNN50 may represent risk factors for accidental syncope.

PMID- 23855069
TI  - Gender effects on mental rotation in pilots vs. nonpilots.
AB  - INTRODUCTION: Mental rotation ability has an important role in human navigation
      and, together with other cognitive abilities such as processing speed, working
      memory, and attention, is crucial for aircraft navigation. In the human
      performance literature, mental rotation tasks have consistently yielded reports
      of gender differences favoring men. The aim of this study was to compare the
      gender difference measured in a specialized population of aviators vs. a matched
      population of nonpilots. METHODS: : Studied were 41 pilots (20 men and 21 women)
      and 38 nonpilots (20 men and 18 women) matched for age and education. Pilots were
      stratified for flying hours. Participants performed a mental rotation task (MRT)
      in which accuracy and response time were recorded, and also completed sense-of
      direction (SOD) and spatial cognitive styles self-evaluation scales. RESULTS: Men
      had significantly smaller response time in the MRT (men 279.6 +/- 147.0 s, women
      401.6 +/- 361.3) and greater SOD (men's score 49.1 +/- 8.6, women's score 46.6 +/
      7.8), but these differences were absent among pilots. A positive relationship
      was also identified between pilots' response times and their flight hours.
      CONCLUSION: These data suggest that the effect of gender on the speed of
      cognitive spatial processing is absent in a population with aviation experience.
      Gender effects may be associated with a low spatial cognitive style, whereas in
      groups such as aviators, who are expected to have high spatial cognitive style,
      other factors such as experience may come into play.

PMID- 23855070
TI  - Two reports of flight-related headache.
AB  - BACKGROUND: Airplane headache is flight-related and appears during airplane
      landing and/or takeoff without accompanying symptoms. Intracranial and paranasal
      imaging studies reveal no abnormalities. The etiology is still uncertain,
      although sinus barotrauma has been proposed as a possible mechanism. CASE
      REPORTS: 1) A 26-yr-old woman presented with recurring headache during each air
      travel since she was 22 yr old. Severe bursting pain suddenly manifested in the
      bilateral orbits and temples during airplane descent, with no accompanying
      additional symptoms. She had no unusual medical history. X-ray computed
      tomography (CT) scans showed no abnormalities except thickening of the nasal
      mucosa. Effective pain relief was obtained with over-the-counter nasal
      decongestant spray. 2) A 49-yr-old man presented with a 3-yr history of flight
      related headache that appeared at airplane touchdown, when he had mental stress,
      or when he was suffering from a lack of sleep. Pain was of a severe jabbing
      quality, localized over the forehead with no additional accompanying symptoms. He
      had a past history of episodic tension-type headache. Intracranial and paranasal
      CT scan revealed no abnormalities. Headache ceased spontaneously within 40 min of
      the end of the flight and nonsteroidal anti-inflammatory drug premedication did
      not prevent the headache. DISCUSSION: Sinus barotrauma was thought to be a
      plausible explanation for the headache in Case 1. In Case 2, an anxiety disorder
      could be considered as an underlying etiology. The etiology of so-called airplane
      headache is probably protean and this should be taken into account when assessing
      cases of in-flight cephalalgia.

PMID- 23855071
TI  - Centrifuge-induced neck and back pain in F-16 pilots: a report of four cases.
AB  - INTRODUCTION: Early in their careers, as an important part of their training to
      become fighter pilots, pilots undergo centrifuge training in order to learn
      effective anti-G straining maneuvers (AGSM) and to test their G tolerance. The
      exposure of pilots, especially early in their careers, to training that could
      lead to injuries should be avoided. This is a report of four cases of neck pain
      experienced during G-tolerance training, some of which may have caused ongoing
      problems for the pilot. CASES: Four cases, describing four different injuries
      experienced during G-tolerance training, are presented, including the history of
      the incident, radiographic description, and physical examination. DISCUSSION:
      Three main questions were identified in regards to the training of fighter pilots
      in centrifuges: 1) should the seat be positioned to imitate a specific aircraft's
      seat? 2) should the pilot wear a helmet and a mask? 3) what is the appropriate
      amount of head support? Based on the four cases reported it is recommended that
      pilots should be given the best possible conditions concerning neck support and
      load on the neck and the back for G-tolerance testing. Training the pilot in an
      anatomical neutral sitting position, without a helmet, and with maximal neck
      support minimizes head movements in cases of conscious or unconscious loss of
      muscle control. To test the stability of the neck in a setup similar to the
      environment where the pilot is going to operate, the pilot should be given the
      opportunity to prepare himself or herself accordingly in advance.

PMID- 23855072
TI  - Use of an adjustable hand plate in studying the perceived horizontal plane during
      simulated flight.
AB  - BACKGROUND: Quantitative data on spatial orientation would be valuable not only
      in assessing the fidelity of flight simulators, but also in evaluation of spatial
      orientation training. In this study a manual indicator was used for recording the
      subjective horizontal plane during simulated flight. METHODS: In a six-degrees-of
      freedom hexapod hydraulic motion platform simulator, simulating an F-16 aircraft,
      seven fixed-wing student pilots were passively exposed to two flight sequences.
      The first consisted in a number of coordinated turns with visual contact with the
      landscape below. The visually presented roll tilt was up to a maximum 670. The
      second was a takeoff with a cabin pitch up of 100, whereupon external visual
      references were lost. The subjects continuously indicated, with the left hand on
      an adjustable plate, what they perceived as horizontal in roll and pitch. There
      were two test occasions separated by a 3-d course on spatial disorientation.
      RESULTS: Responses to changes in simulated roll were, in general, instantaneous.
      The indicated roll tilt was approximately 30% of the visually presented roll.
      There was a considerable interindividual variability. However, for the roll
      response there was a correlation between the two occasions. The amplitude of the
      response to the pitch up of the cabin was approximately 75%; the response decayed
      much more slowly than the stimulus. DISCUSSION: With a manual indicator for
      recording the subjective horizontal plane, individual characteristics in the
      response to visual tilt stimuli may be detected, suggesting a potential for
      evaluation of simulation algorithms or training programs.

PMID- 23855073
TI  - Central nervous system symptoms in U-2 pilots.

PMID- 23855074
TI  - In response.

PMID- 23855075
TI  - Going beyond anesthesia in space exploration missions: emergency medicine and
      emergency medical care.

PMID- 23855076
TI  - In response.

PMID- 23855077
TI  - Implementing performance moderators for non-player characters in commercial
      gaming environments.

PMID- 23855078
TI  - You're the flight surgeon: anaphylactoid reaction.

PMID- 23855079
TI  - You're the flight surgeon: celiac disease.

PMID- 23855080
TI  - This month in aerospace medicine history.

PMID- 23855081
TI  - Vaginal delivery after caesarean section.
AB  - The trend to deliver with caesarean section has increased in the recent years.
      The factors affecting this trend need re-consideration. Most of the women would
      deliver normally after a trial of labour alter previous caesarean section. The
      obstetricians should abide by ethics in clinical practice, carefully evaluate the
      indication before every caesarean section, and take an unbiased decision before
      performing a caesarean section.

PMID- 23855082
TI  - Changing haematological parameters in dengue viral infections.
AB  - BACKGROUND: Dengue Fever is the most common arboviral disease in the world, and
      presents cyclically in tropical and subtropical regions of the world. The four
      serotypes of dengue virus, 1, 2, 3, and 4, form an antigenic subgroup of the
      flaviviruses (Group B arboviruses). Transmission to humans of any of these
      serotypes initiates a spectrum of host responses, from in apparent to severe and
      sometimes lethal infections. Complete Blood count (CBC) is an important part of
      the diagnostic workup of patients. Comparison of various finding in CBC including
      peripheral smear can help the physician in better management of the patient.
      MATERIAL AND METHODS: This cross sectional study was carried out on a series of
      suspected patients of Dengue viral infection reporting in Ittefaq Hospital
      (Trust). All were investigated for serological markers of acute infection.
      RESULTS: Out of 341 acute cases 166 (48.7%) were confirmed by IgM against Dengue
      virus. IgG anti-dengue was used on 200 suspected re-infected patients. Seventy
      one (39.5%) were positive and 118 (59%) were negative. Among 245 confirmed dengue
      fever patients 43 (17.6%) were considered having dengue hemorrhagic fever on the
      basis of lab and clinical findings. Raised haematocrit, Leukopenia with relative
      Lymphocytosis and presence atypical lymphocytes along with plasmacytoid cells was
      consistent finding at presentation in both the patterns of disease, i.e., Dengue
      Haemorrhagic fever (DHF) and Dengue fever (DF). CONCLUSION: Changes in relative
      percentage of cells appear with improvement in the symptoms and recovery from the
      disease. These findings indicate that in the course of the disease, there are
      major shifts within cellular component of blood.

PMID- 23855083
TI  - Gestational trophoblastic disease.
AB  - BACKGROUND: Molar pregnancy represents a significant burden of disease on the
      spectrum of Gestational Trophoblastic Disease (GTD). The incidence appears to be
      quite high in South Asia. The objective of this study was to determine the
      frequency of GTD, and clinical presentation, management and outcome of patients
      with molar pregnancy. METHODS: This retrospective, descriptive study was
      conducted at Nuclear Institute of Medicine and Radiotherapy (NIMRA), Jamshoro
      from 1st Jan to 31st Dec 2009. All patients diagnosed and registered as GTD were
      included in the study. The clinical records of all molar patients were reviewed
      regarding presentation, treatment, and follow-up. RESULTS: There were a total of
      167 patients presenting with different female genital tract neoplasia at NIMRA
      during the study period, including 39 (29.35%) cases of GTD. Hydatidiform mole
      was seen in 33 (84.61%) patients. Complete mole in 31 (79.48%), partial mole in 2
      (5.12%) patients, invasive mole in 1 (2.56%) patient, and choriocarcinoma in 5
      (12.82%) patients. The mean age of the patients was 27 +/- 9.8 years. The highest
      incidence was found in nulliparous and para 1. Thirty-two patients had suction
      evacuation and 1 patient underwent hysterectomy. Patients received chemotherapy,
      17 (54.54%) patients followed protocol for 3-6 months. CONCLUSION: Frequency of
      molar pregnancy was high, more common in low-parous, poor socioeconomic class
      women, and usually presented late.

PMID- 23855084
TI  - Maternal morbidity in emergency versus elective caesarean section at a tertiary
      care hospital.
AB  - BACKGROUND: In the past 30 years the rate of caesarean section (C/S) has steadily
      increased from 5% to more than 20% for many avoidable and unavoidable
      indications. The objective of this study was to compare maternal morbidity and
      determine its cause in elective and emergency caesarean section. METHOD: It was a
      cross-sectional comparative study conducted in Civil Hospital Karachi at Obs/Gyn
      Unit III. All mothers admitted through OPD or emergency during the study period,
      of any age or parity undergoing C/S were recruited in the study. Patients having
      previous myomectomy, hysterotomy or classical C/S were excluded from the study.
      Patients undergoing emergency C/S were placed in group A, and those delivered by
      elective C/S were included in group B. Study variables were general and obstetric
      parameters and complications observed intra-operatively. Any postoperative
      complications were recorded from recovery room till patient was discharged from
      the ward. RESULTS: There were 50 patients in each group. In group A, 11 (22%)
      were booked and 33 (66%) were referred cases. In group B, 48 (96%) were booked.
      The mean age in both groups was 28 years. In both groups, multigravida compared
      to primigravida were 78% vs 22% in group A, and 92% vs 8% in group B. Indication
      for C/S was previous C/S in 10 (20%) patients in group A, and 39 (78%) patients
      in group B, placenta previa, chorioamionitis, obstructed labour (6, 12% each);
      pregnancy induced hypertension and eclampsia in 5 (10%) cases in group A only.
      Intra-operative complications in group A were 48 (96%) vs 15 (30%) in group B (p
      = 0.000). Postoperative morbidity in group A was 50 (100%) and 26 (52%) in group
      B (p = 0.000). Intra-operative complication was haemorrhage in 46 (92%) cases in
      group A and 11 (22%) in group B. Anaesthetic complications were 40 (80%);
      prolonged intubation 25 (50%), aspiration of gastric contents 8 (16%), and
      difficult intubation 7 (14%) in group A. Ten (20%) cases had anaesthetic
      complications in group B. Commonest postoperative complication in both groups was
      anaemia in 41 (82%) and 11 (22%) cases respectively. CONCLUSION: Maternal
      morbidity is significantly higher in emergency C/S. Haemorrhage is a frequent
      complication in C/S, emergency or elective.

PMID- 23855085
TI  - A ten year review of emergency peripartum hysterectomy in a tertiary care
      hospital.
AB  - BACKGROUND: Emergency peripartum hysterectomy (EPH) is a life saving procedure
      considered in cases of severe haemorrhage unresponsive to medical and
      conservative surgical procedures. The aim of present study was to review the
      frequency, indications, maternal morbidity and mortality associated with
      emergency peripartum hysterectomy in a tertiary care hospital in a developing
      country. METHODS: This was a cross sectional study in which data was
      retrospectively collected from January 2000 to December 2010. Main outcome
      measures were maternal morbidity and mortality associated with EPH. RESULTS: The
      incidence of EPH was 10.52/1000 deliveries. The main causes of EPH were rupture
      uterus 76 (34.86%), atonic uterus 65 (29.81%), placenta accreta 19 (8.71%),
      placenta previa 17 (7.7%), and placental abruption 36 (16.5%). Mostly subtotal
      hysterectomy was the preferred method done in 196 (89.9%) of cases, while total
      abdominal hysterectomy was done only in 22 (10.09%) of cases. The over all
      complication rate was 81.2% which included both minor and major complications
      like hypovolemic shock 180 (82.5%), febrile morbidity 108 (49.5%), wound
      infection 40 (18.3%), bladder injury 6 (2.75%), and thrombophlebitis 22 (10.09%).
      The maternal mortality in present review was (10.5%). CONCLUSION: Frequency of
      EPH was found to be high in this study. Obstetricians must be skilled in it
      particularly in developing countries where the main indication of hysterectomy is
      rupture uterus.

PMID- 23855086
TI  - Choledochorraphy (primary repair) versus t-tube drainage after open
      choledochotomy.
AB  - BACKGROUND: T-tube drainage used to be standard practice after surgical
      choledochotomy, but there is now a tendency in some canters to close the common
      bile duct primarily. This study was designed to compare the clinical results of
      primary closure with T-tube drainage after open choledocotomy and assess the
      safety of primary closure for future application. METHODS: This study was
      conducted at surgical Unit-3, ward 26 Jinnah Postgraduate Medical Centre Karachi,
      from January 2007 to January 2008. Forty patients were included in this study out
      of which 20 underwent primary closure and 20 T-tube placements. It was Quasi
      experimental, non-probability, purposive sampling. Main outcome measures were
      operating time, duration of hospital stay, and postoperative complications. SPSS
      10 was used for data analysis. RESULTS: The age of patients in the study ranged
      from 29-83 years. There were 3 male while 37 female patients. Group-1 consisted
      of 20 patients underwent primary closure after choledocotomy, while Group-2 also
      consisted of 20 patients underwent T-tube drainage after duct exploration. Mean
      hospital stay in Group-1 patients was 7.63 days while in group 2 it was 13.6
      days. Overall complication rate in group 1 was 15%, biliary leakage in 1 (5%),
      jaundice in 1 (5%), wound infection in 1 (5%). No re-exploration was required in
      Group-1. In Group-2 overall complication rate was 30%, biliary leakage in 2 (2%),
      jaundice in 1 (5%), dislodgement of T-tube in 1 (5%), wound infection in 1 (5%),
      and sepsis in 1 (5%) patients. Re-exploration was done in one patient.
      CONCLUSION: Primary closure of Common Bile Duct (CBD) is a safe and cost
      effective alternative procedure to routine T-tube drainage after open
      choledocotomy.

PMID- 23855087
TI  - Efficacy and side effects of glyceryl trinitrate in management of chronic anal
      fissure.
AB  - BACKGROUND: Various options are available for treatment of chronic anal fissure,
      each with its own associated complications. This study aimed to evaluate the
      efficacy of topical Glyceryl Trinitrate (GTN) for anal fissures in an outpatient
      setting. METHODS: A prospective experimental study was carried out at the
      outpatient department of Surgical Unit IV, Liaquat University Hospital from Aug
      2004 to Jul 2005. Total 100 patients fulfilling the criteria of chronic anal
      fissure were included in the study. Patients presenting with chronic anal fissure
      but with associated comorbidities were excluded. Data were collected on a
      designed questionnaire, and analysed using SPSS-10. RESULTS: Sixty women and 46
      men were included in the study with a mean age of 30 years. After the end of 8
      weeks of treatment, 76 showed healing of fissure and relief in symptoms whereas
      20 patients either had improvement in symptoms or did not heal. The commonest
      side-effect was headache reported by 21 patients. The minimum period of follow-up
      was one year, and 7 patients had recurrence. CONCLUSION: Topical 0.2% GTN is an
      effective first-line agent in managing chronic anal fissure. The associated side
      effects and recurrence remains a matter of concern.

PMID- 23855088
TI  - Patient satisfaction for levonorgestrel intrauterine system and norethisterone
      for treatment of dysfunctional uterine bleeding.
AB  - BACKGROUND: Dysfunctional uterine bleeding (DUB) is a common problem with complex
      management. It can be quite harrowing for the physicians as in most instances
      they are unable to pinpoint the cause of abnormal bleeding even after a thorough
      history and physical examination. Aim was to compare patient satisfaction for
      Levonorgestrel intra uterine system (LNG-IUS) and Norethisterone for the
      treatment of Dysfunctional Uterine Bleeding (DUB). It is Descriptive case series
      conducted in Department Obstetrics and Gynaecology, Shifa International Hospital,
      Islamabad from September, 2011 to September, 2012. METHODS: One hundred and
      nineteen (119) female patients of reproductive age Group with DUB were selected
      by consecutive sampling. Informed written consent was obtained. A structural
      patient satisfaction questionnaire (PSQ) was used to collect information
      regarding age of patients, type of method used for treatment of DUB
      (Levonorgestrel or Norethisterone), treatment outcome in terms of patient
      satisfaction scale, and decrease in bleeding after 6 months. RESULTS: The mean
      age of the patients was 41.03 +/- 4.415 year ranging from 28-60 years. The mean
      parity of women in the study was 3.22 +/- 1.188 with a range of 1-7. The
      satisfaction level was significantly (p < 0.05) greater (90% versus 20%) in Group
      A (levonorgesterol-releasing intrauterine system) as compared with Group B
      (Norethisterone). The blood loss was significantly (p < 0.05) decreased in Group
      A (98%) as compared with Group B (80%). The preference of continuing the method
      as well as recommendation to a friend was significantly greater in Group A as
      compared to Group B. CONCLUSION: The levonorgesterol-releasing intrauterine
      system (LNG-IUS) is a better choice as compared to Norethisterone, for treatment
      of DUB with 90% patients highly satisfied.

PMID- 23855089
TI  - Experience of laparoscopic cholecystectomy during a steep learning curve at a
      university hospital.
AB  - BACKGROUND: Cholelithiasis is the most common disease of alimentary tract
      affecting the adult population globally and our country in particular is no
      exception to it as a cause of hospitalization. Surgical removal of gall bladder
      is the main stay of symptomatic cholelithiasis ensuring a permanent cure. The
      minimally invasive technique of laparoscopic cholecystectomy has gained wide
      acceptance as a Gold Standard treatment ever since its introduction. The purpose
      of this prospective observational study was to document our experience of
      laparoscopic Cholecystectomy during a learning curve in a single unit of a
      university hospital and compare it with other available data in the literature.
      METHODS: Total 94 patients underwent laparoscopic cholecystectomy during the
      learning curve from Jan 2009 to Dec 2010 in the Department of Surgery Liaquat
      University Hospital Jamshoro. RESULTS: Mean age was 42 years with females
      (88.29%) preponderance. Majority of the cases were operated by consultants
      (85.10%) within 25-60 minutes. Postoperative hospital stay was 3 days with return
      to work in 7 days. Only 6 (6.38%) cases were converted to open technique. Intra
      peritoneal drains and Foley's catheter were kept in selected cases only. Eleven
      patients (11.70%) had intra-operative complications including complete
      transaction of CBD in only one (1.06%) male patient. Five patients (5.31%) had
      postoperative complications with two patients having iatrogenic duodenal injury
      which was not identified during surgery and pseudo cyst pancreas. Four patients
      (4.25%) died due to multiple organ failure. CONCLUSION: We conclude that
      Laparoscopic Cholecystectomy is a gold standard procedure and should be learned
      on virtual simulated models before starting this procedure on human patients.

PMID- 23855090
TI  - Frequency of unerupted mandibular third molar in mandibular angle fractures.
AB  - BACKGROUND: Fractures of the mandibular angle are common and comprise 31% of all
      mandibular fractures. Multiple recent studies report a 2-3 fold increased risk
      for mandibular angle fractures when un-erupted mandibular third molars are
      present. The objective of this study was to assess the frequency of un-erupted
      mandibular third molar in mandibular angle fractures. METHODS: This cross
      sectional study was conducted at the Department of Oral and Maxillofacial
      Surgery, Ayub Medical College, Abbottabad from April to October 2009. One hundred
      and two patients were included both from the outdoor and ward on consecutive non
      probability sampling base. Data were recorded on a structured Performa and
      analysed using SPSS-16. RESULTS: A hemi-mandible containing un-erupted mandibular
      third molar was seen to have a 1.41 times the risk of mandibular angle fracture
      then a hemi-mandible containing an erupted mandibular third molar. CONCLUSION:
      The presence of unerupted mandibular third molar is associated with an increased
      risk for mandibular angle fracture.

PMID- 23855091
TI  - Aetiology and types of neonatal seizures presenting at Ayub Teaching Hospital
      Abbottabad.
AB  - BACKGROUND: Neonatal seizures (NS) affect approximately 1% of neonates. Clonic,
      tonic, myoclonic and subtle seizures are the common types. Birth asphyxia,
      sepsis, metabolic derangements, intracranial bleed, kernicterus, tetanus and 5th
      day fits are the common aetiologies. This study was planned to evaluate the types
      and causes of neonatal seizures. METHODS: It was a descriptive case series
      conducted at Ayub Teaching Hospital, Abbottabad from 12th December 2006 to 25th
      September 2007 on neonates having seizures. Serum chemistry, blood counts,
      cerebrospinal fluid examination and cranial ultrasound were done in all patients.
      Blood culture, renal and liver function tests, computerised tomography scan,
      metabolic and septic screening was done in selected patients. Descriptive
      statistics were applied for analysis. RESULTS: Tonic clonic seizure was the
      commonest type (28%) followed by multi-focal clonic, and focal tonic seizures
      (25% each). Birth asphyxia was found to be the main aetiology (46%). CONCLUSION:
      Tonic clonic seizure was the commonest type and birth asphyxia the main aetiology
      identified in the majority of neonatal seizures.

PMID- 23855092
TI  - Feasibility and safety of transabdominal chorionic villus sampling.
AB  - BACKGROUND: Chorionic Villus Sampling (CVS) is the technique of choice for
      prenatal diagnosis prior to 12 weeks gestation. The objective of this study was
      to determine the feasibility, and pattern of complications following first
      trimester Trans-abdominal Chorionic Villus Sampling (TA-CVS). METHODS: This was a
      descriptive study conducted in the Obstetrics and Gynaecology Department Military
      Hospital (MH) Rawalpindi from Jan 2007 to July 2008. Couples at risk of giving
      birth to a child with genetic disorder were identified and counselled. Trans
      abdominal Chorionic Villus Sampling was done using double needle technique under
      ultrasound guidance. Immediate and late complications were followed up. Data was
      analysed using SPPS-10. RESULTS: On 200 cases chorionic villus sampling was done
      as an outdoor procedure. Most common indication was thalassaemia trait 75
      (37.5%). Most procedures were done between 12-13 weeks. All placental positions
      including 104 (52%) posterior and 71 (35.5%) anterior were approachable. Most
      aspirations were easy, however, in 30 (15%) the aspiration was difficult. Overall
      success rate was 100%. In 158 (79%) of the cases sample yield was good. One
      (0.5%) patient had vaginal bleeding and three (1.5%) had placental haematoma
      formation. Most patients (84%) experienced mild pain during the procedure. The
      procedure related miscarriage occurred in 2 (1%) patients while another patient
      developed this complication after 6 weeks. CONCLUSION: First trimester TA-CVS is
      an accurate and safe invasive prenatal diagnostic procedure. Placentas in almost
      any position can be approached without any significant risk to mother and the
      foetus.

PMID- 23855093
TI  - Early complications of elective and emergency tracheostomy.
AB  - BACKGROUND: Tracheostomy is a life saving procedure when it is performed for an
      appropriate indication and surgical technique. The aim of this study was to
      compare the early complications of elective and emergency tracheostomy in our
      setup. METHODS: This comparative study was conducted at the ENT Department.
      Hayatabad Medical (Complex (HMC) from March 2009 to March 2010. A total of 100
      patients included in this study were divided in to two equal groups, group A
      undergoing elective tracheostomy and group B undergoing emergency tracheostomy.
      The results of hundred patients were compared and analysed from stand point of
      age, sex, disease pattern, operative procedure and postoperative complications
      associated with tracheostomy. RESULTS: A total of 100 patients were included with
      age ranging from 17 to 88 years. The average age was 35 years in elective cases
      and was 32 years in emergency cases. The male to female ratio was 2.9:1 in
      elective cases and 4.6:1 in emergency cases. The overall complications rates were
      38% in elective cases and 56% in emergency cases. CONCLUSION: Early complications
      of emergency tracheostomy are more common than elective tracheostomy.

PMID- 23855094
TI  - Death in the home: domestic violence against women in Khyber Pakhtunkhwa.
AB  - BACKGROUND: Domestic or Interpersonal Violence (IPV) remains a major global
      problem often resulting in morbidity and mortality. The present study was
      conducted to determine the scope of deaths related to domestic violence in the
      Khyber Pakhunkhwa province, Pakistan. METHODS: Data were collected on all
      reported female fatalities due to domestic violence for the years 2009-2011 from
      the records of the department of Forensic Medicine, Khyber Medical College
      Peshawar for analysis. RESULTS: A total of 305 deaths were reported, showing an
      increasing trend of 115 deaths for 2009-10 and 190 deaths for 2010-2014. The
      majority, 182 (59.7%) belonged to the rural areas and 123 (40.3%) to urban areas
      of the province. Victims were generally of the younger age groups (17% below age
      16 and 42.3% between 17-32 years). Homicide was the manner of death in 293
      (96.1%) while the most common causative agent was firearm injury (235, 77.1%).
      Head and neck injuries were most common (52.6%) followed by the chest and abdomen
      (31.6%) while multiple sites and extremities accounted for 15.8% of injuries.
      CONCLUSION: Young and adult females of KPK province of Pakistan are susceptible
      to homicidal deaths due to domestic violence, perpetrated through firearm
      injuries to the head and neck regions.

PMID- 23855095
TI  - Dermatological manifestations of dengue fever.
AB  - BACKGROUND: Each year dengue related infections are rising in tropical countries.
      There is not enough data available on dermatological manifestations of dengue
      fever. This study was conducted to investigate prevalence and type of
      dermatological manifestations of dengue fever (DF). Dengue Haemorrhagic Fever
      (DHF), and Dengue Shock Syndrome (DSS). METHODS: A Prospective study was
      contacted in Department of Medicine, Shaikh Zayed Hospital, Lahore, from 3rd Oct
      to 20th Nov 2010. Specific serological tests for DF were done in all 60 patients
      admitted with suspected diagnosis of DF, DHF or DSS. Forty-eight confirmed cases
      were evaluated for age, gender, mucocutaneous features and outcome of the
      disease. RESULTS: Forty-eight out of 60 patients had positive serology for dengue
      fever. Male to female ratio was 1.09:1. Their ages ranged 5-68 years with a mean
      of 31.5 +/- 15.2. DF, DHF and DSS were found in 71%, 19% and 10% respectively.
      Common dermatological presentations were oral mucous membrane congestion
      (66.67%), generalised morbiliform rash (64.58%) and eye congestion (64.58%).
      Purpuric spots along with mucous membrane congestion, generalised morbiliform
      rash and eyes congestion was observed in 20.83%, 12.5% and 6.25% patients
      respectively. All except one patient improved clinically. One patient died of
      respiratory distress and haemorrhage on second day of admission. CONCLUSION:
      Dermatological features are significantly noticeable in dengue fever patients.
      These may help us in early diagnosis and better management of patients.

PMID- 23855096
TI  - Effects of ciprofloxacin and zinc chloride in adult albino rat and pre-natal
      conceptus.
AB  - BACKGROUND: Administration of quinolone therapy is controversial during growing
      age as stated by earlier authors. The flouroquinolones are currently not
      indicated for young children because of arthropathy and adverse effect as new
      born shown by studies. However the effects of ciprofloxacin and ZnCl2 on prenatal
      conceptus have remained undocumented. The present study was designed to compare
      the effects on conceptus after maternal ingestion of ciprofloxacin and ZnCl2
      using Wastar albino rats. METHODS: Ciprofloxacin and ZnCl2 was administrated to
      pregnant female albino rats. Ciprofloxacin with a dose of 20 mg/Kg bodyweight and
      ZnCl2 120 microg/100 gm bodyweight two times therapeutic dose for 10 days (from
      day 8-18 of pregnancy). Each animal was weighted on day 1, day 8 and day 18 of
      pregnancy. Abortion resulted on day 18th of pregnancy. Each group of pregnant
      animals were sacrificed on day 18 of gestation by over dose of either
      anaesthesia, abdomen opened, uterus and both cornua containing conceptus
      identified, removed, there weight recorded, crown rump length was measured and
      was compared with similar value of control animals. The results were
      statistically analysed to find out the significance. RESULTS: The ciprofloxacin
      induces a mordanting effect as obviated by increased basophilia. Our study
      reveals that ciprofloxacin administered in maternal, decreased maternal body
      weight to 38.4 +/- 0.9 gm. However simultaneous ZnCl2 maintained the body weight
      to 41.4 +/- 0.7 gm, while ZnCl2 increased the body weight to 46.5 +/- 2.25 gm.
      The body weight and Crown Rump length (CR Length) in conceptus decreased by 4.52
      +/- 0.10 gm and 3.06 +/- 0.09 Cm respectively. That ciprofloxacin and ZnCl2
      administration maintained the body weight and CR length by 5.46 +/- 0.09 gm and
      3.79 +/- 0.13 Cm respectively. That ZnCl2 administration increased the body
      weight and CR length by 6.71 +/- 0.05 gm and 4.15 +/- 0.08 Cm respectively.
      CONCLUSION: Prenatal administration of Ciprofloxacin caused reduction in growth
      rate and CR length, and ZnCl2 maintained body weight and CR length and growth of
      the rat conceptus.

PMID- 23855097
TI  - Serum homocysteine as a risk factor for coronary heart disease.
AB  - BACKGROUND: Homocysteine (Hcy) is an intermediate formed during the catabolism of
      sulphur containing essential amino acid, methionine and Less than one percent of
      tHcy is found as the free form. Development of atherosclerotic changes and
      thrombo-embolism are common features in patients with homocysteinuria. This study
      was conducted to assess the relationship of Hcy and coronary heart disease (CHD)
      in our population. METHODS: The cross-sectional analytical study was carried out
      at the Department of Biochemistry, Hazara University Mansehra and Ayub Medical
      College, Abbottabad. A total of 80 subjects were included in this study and were
      divided into 2 groups. Cases Group consisted of 40 patients who had confirmed
      Myocardial Infarction (MI) coming for routine follow-up (first re-visit) after
      the acute attack. Control Group consisted of 40 matching healthy individuals.
      Demographic data including age, gender, dietary habits, height and weight as
      documented in preformed proforma. Blood pressure was taken in sitting posture.
      Serum total Hcy were measured. Data was entered into computer using SPSS 16.0 for
      analysis. RESULTS: The mean age of the cases was 59.68 +/- 8.06 (30-70) years and
      that of the controls was 58.93 +/- 6.93 (48-76) years. The average BMI of cases
      was 27.70 +/- 3.61 Kg/m2 and of the controls was 25.66 +/- 2.98 Kg/m2. This
      increase of BMI from controls to cases was statistically significant (p < 0.050).
      The mean systolic BP of the cases was 153.88 +/- 11.90 mmHg in comparison with
      142.62 +/- 11.65 mmHg for the controls. This difference was statistically
      significant (p < 0.001). Mean tHcy level of the cases was 17.15 +/- 4.45
      micromol/l while that of controls was 12.20 +/- 2.53 micromol/l. There is a
      statistically significant difference between cases and controls with respect to
      Hcy levels (p < 0.001). CONCLUSION: Plasma tHcy level has a powerful predictor
      value of CHD and routine screening for elevated Hcy concentrations is advisable
      especially for individuals who manifest atherothrombotic disease without their
      traditional risk factors.

PMID- 23855098
TI  - Pattern of magnetic resonance imaging and magnetic resonance venography changes
      in cerebral venous sinus thrombosis.
AB  - BACKGROUND: Cerebral venous sinus thrombosis is a common but highly under
      recognised condition, which is missed not only by general practitioners but also
      by neurologists. Computerised tomography (CT) or magnetic resonance imaging (MRI)
      of brain alone is not sufficient to diagnose this condition. Objective of this
      study was to explore the pattern of magnetic resonance imaging (MRI) and magnetic
      resonance venography (MRV) changes in cerebral venous sinus thrombosis (CVST).
      METHODS: This was a descriptive study in which 52 cases of cerebral venous sinus
      thrombosis with special emphasis on their MRI and MRV findings were included. The
      study was conducted in Neurology Unit, Lady Reading Hospital, Peshawar, Pakistan,
      from January 2010 to July 2011. All patients suffering from cerebral venous sinus
      thrombosis were included in the study. Multi-planar/multi-sequential, Tesla 1.5
      MRI/MRV time of flight images were done in all cases where there was suspicion of
      cerebral venous sinus thrombosis. RESULTS: Out of 52 patients with cerebral
      venous sinus thrombosis 41 (78.84%) were female and 11 (21.15%) were male. Mean
      age was 37 +/- 5 years. Definite risk factors were found in 38 (73.076%) patients
      with pregnancy, use of oral contraceptives or puerperium being the most
      frequently found risk factor in 20 (73.076%) patients. Most common complaint was
      headache found in 41 (78.84%) patients, followed by focal neurological deficits,
      and altered mental status and seizures. Papilloedema was seen in 20 (38.46%)
      patients. The cerebral venous sinuses most frequently involved were transverse
      and sigmoid sinuses in 17 patients (32.69%) while superior sagittal sinus alone
      in 10 (19.23%) patients. Overall CT brain was normal in 30% and MRI brain in
      23.07% patients; however, MRV of these patients revealed CVST. CONCLUSION:
      Imaging plays a primary role in the diagnosis of cerebral venous sinus thrombosis
      because the clinical picture of CVST is non-specific and highly variable.
      Thrombosis of cerebral venous system is readily picked-up on MRV even if it is
      missed by CT scan or MRI.

PMID- 23855099
TI  - Comparative analysis of type of myocardial infarction in patients with successful
      or unsuccessful streptokinase thrombolysis following ST elevation myocardial
      infarction.
AB  - OBJECTIVE: To study the effect of thrombolytic therapy in term of success and
      failure on the type of ST elevation MI, using streptokinase. MATERIAL AND
      METHODS: This was a comparative study, conducted at Department of Cardiology,
      Lady Reading Hospital, Peshawar, from October 2006 to October 2007. Patients with
      first acute myocardial infarction were divided into group A (successful
      thrombolysis) and group B (unsuccessful thrombolysis) using ECG criteria.
      RESULTS: Total number of patients were 200. Group A included 136 (68%) patients
      and group B included 64 (32%) patients. There were total 88 (44%) patients of
      anterior MI with 47 patients in group A and 41 patients in group B (34.6% vs
      64.0%, p < 0.001). There were total 110 (55.0%) patients of inferior MI with 88
      patients in group A and 22 patients in group B (64.7% vs 34.4%, p < 0.001).
      Lateral myocardial infarction was diagnosed in 2 (1%) patients with 1 patient
      each in group A and group B (0.7% vs 1.6%, p = 0.583). CONCLUSION: Anterior MI
      was associated with a higher rate of thromblysis failure while inferior MI and
      lateral wall MI was associated with a higher rate of successful thrombolysis.

PMID- 23855100
TI  - Frequency of conservatively managed traumatic acute subdural haematoma changing
      into chronic subdural haematoma.
AB  - BACKGROUND: Traumatic brain injury represents a significant cause of mortality
      and permanent disability in the adult population. Acute subdural haematoma is one
      of the conditions most strongly associated with severe brain injury. Knowledge on
      the natural history of the illness and the outcome of patients conservatively
      managed may help the neurosurgeon in the decision-making process. METHODS: We
      prospectively analysed 27 patients with age ranges 15-90 years, in whom a CT scan
      diagnosis of acute subdural haematoma was made, and in whom craniotomy for
      evacuation was not initially performed, to the neurosurgery department of Ayub
      Teaching Hospital Abbottabad (2008-2011). Patients with deranged bleeding
      profile, anticoagulant therapy, chronic liver disease, any other associated
      intracranial abnormalities, such as cerebral contusions, as shown on CT, were
      excluded from this study. All patients were followed by serial CT scans, and a
      neurological assessment was done. RESULTS: There were 18 male and 9 female
      patients, Cerebral atrophy was present in over half of the sample. In 22 of our
      patients, the acute subdural haematoma resolved spontaneously, without evidence
      of damage to the underlying brain, as shown by CT or neurological findings. Four
      patients subsequently required burr hole drainage for chronic subdural haematoma.
      In each of these patients, haematoma thickness was greater than 10 mm. The mean
      delay between injury and operation in this group was 15-21 days. Among these
      patients 1 patient required craniotomy for haematoma removal due to neurological
      deterioration. CONCLUSION: Certain conscious patients with small acute subdural
      haematomas, without mass effect on CT, may be safely managed conservatively, but
      due to high risk of these acute subdural haematoma changing into chronic subdural
      haematoma these patients should be reinvestigated in case of neurological
      deterioration.

PMID- 23855101
TI  - Surgical treatment in lumbar spondylolisthesis: experience with 45 patients.
AB  - BACKGROUND: Spondylolithesis is forward slipping of upper vertebra in relation to
      its lower one, which at times requires surgery. The objective of present study is
      to document the outcome of surgical treatment in spondylolisthesis of lumbosacral
      region. METHODS: We reviewed outcome of surgery in 45 patients with
      spondylolisthesis. Improvement in pain intensity, neurological status and union
      achieved after surgery was studied. All patients requiring surgical treatment
      were included in the study. The patients were operated by single spine surgeon. A
      Performa was made for each patient and records were kept in a custom built
      Microsoft access database. RESULTS: Majority of our patient were in 4th and 51th
      decade with some male domination. Pain was main indication for surgery which was
      excruciating in 6. severe in 33, and moderate in 6 cases. The neurological status
      was normal in 34 cases while 11 patients had some deficit. L5-S1 was affected in
      26, L4-L5 in 13 and multi or high level was found in rest of cases. Slip grade
      was measured with Meyerding grades, 18 had grade II, 15 had I, 9 had III and 3
      had IV spondylolisthesis. Posterior lumbar inter body fusion (PLIF) was done in
      24 patients, posterolateral, transforaminal lumbar inter body and anterior inter
      body fusion in others. Translaminar screw fixation, transpedicular transdiscal
      transcorporial and Delta fixation in some cases. Pedicle screw fixation was done
      in most cases, AO fixator internae and 4.5 mm screw in others. Average follow up
      was 2 years and 5 months, max 5 years and minimum 6 months. Pain relief was
      achieved in 82%, neurological improvement 60% and union in 91% cases. There was
      no deterioration of neurological status, two implant failure and one wound
      infection. CONCLUSION: Surgical procedure for Spondylolisthesis must be
      individualised. Young patients with spondylolysis can be treated with
      osteosynthesis and sparing of motion segment. PLIF provides satisfactory results
      in majority of low to moderate cases with some reduction. Transpedicular
      transdiscal transcorprial and delta fixation is good procedure for severe slips
      in adult.

PMID- 23855102
TI  - Clinical audit of foetomaternal outcome in pregnancies with fibroid uterus.
AB  - BACKGROUND: Leiomyoma, myoma, leiomyoma or fibroids are synonymous terms. They
      may be present in as many as 1 in 5 women over age 35 years. If pregnancy is
      associated with fibroids, it leads to multiple complications. Objectives of this
      study were to evaluate the maternal and foetal outcome in women having pregnancy
      with fibroids in uterus and the complications associated with fibroids during the
      pregnancy. METHODS: This descriptive study was conducted in the Department of
      Obstetrics and Gynaecology, Ayub Teaching Hospital Abbottabad from March 2009 to
      March 2010. Data were collected on performa regarding demographic variables,
      obstetrical history, mode of delivery, maternal outcome, maternal complications,
      and foetal outcome. Mean and standard deviation was calculated for age, period of
      gestation, and obstetrical history. Frequency and percentages was calculated for
      booking status, maternal outcome, maternal complications and foetal outcome.
      RESULTS: Thirty patients were included in this study who had pregnancy with
      fibroid. Normal delivery was achieved in 14 (46.66%) patients. Eight (26.67%)
      patients had caesarean section and eight (26.67%) had miscarriages. Seven
      (23.33%) patients had no complications while 8 (26.67%) had miscarriages, 8
      (26.67%) had postpartum haemorrhage, 10 (33.33%) had preterm delivery, and 3
      patients had ante-partum haemorrhage. Two (10%) patients had premature rupture
      off membranes and 1 patient (3.33%) had pain abdomen and technical difficulty
      during caesarean section. There were 12 (40%) healthy babies. Five (16.67%)
      babies delivered with morbidity but recovered. There were 4 (13.33%) intrauterine
      deaths and one early neonatal death. CONCLUSION: Fibroid in pregnancy, especially
      multiple intramural fibroids and fibroids larger than 10 Cm, cause miscarriage
      and preterm labour.

PMID- 23855103
TI  - Medical versus surgical management of otitis media with effusion in children.
AB  - BACKGROUND: Otitis media with effusion (OME) is a leading cause of hearing
      difficulty in children. OME must be detected early and managed properly to
      prevent hearing and speech impairment in children. This study was aimed to
      compare results of medical and surgical treatments in terms of hearing
      improvement, recurrence of Middle Ear Effusion (MEE), time to offer surgical
      intervention. METHODS: The study was conducted from June 2008 to December 2011. A
      performa was used to collect data. Every child having hearing difficulty was
      examined with pneumatic otoscope for fluid level and tympanic membrane mobility.
      These children were investigated with pure tone audiometry for level of hearing
      loss and tympanometry to confirm the middle ear effusion. X-Ray nasopharynx
      lateral view was taken to see if there were adenoids. All patients were treated
      conservatively in the first phase. Those not responding to conservative treatment
      were treated with myringotomy and adenoidectomy with or without ventilation
      tubes. Patients were followed-up for up to 36 months. RESULTS: Middle ear
      effusion cleared in 80 (71.5%) out of 112 ears. No improvement was noted in 32
      ears for 9 months. Resistant and recurrent cases were managed with adenoidectomy
      and myringotomy alone or with insertion of ventilation tubes (VT). Recurrence was
      noted more common with myringotomy alone than with ventilation tubes. Medical
      treatment failed in 32 ears. MEE recurred in 9 ears. VT was put in 41 ears. The
      hearing level improved with VT by 10-15 dB after first 3 months. CONCLUSION: All
      children with OME should be treated conservatively. It is cost effective and
      relieves MEE in about 70% of patients. The ears with OME that fails to resolve or
      recur should be managed with myringotomy and VT insertion or adenoidectomy.

PMID- 23855104
TI  - Frequency of sensory deficit in terms of two point discrimination in split
      thickness skin grafts and local flaps for soft tissue defects of fingers.
AB  - BACKGROUND: The minimum distance between two stimulus points on the skin, which
      are perceived as distinct points, is defined as two point discrimination (TPD).
      Among the two types of TPD, i.e., static and dynamic, static two-point
      discrimination (STPD) is commonly used to determine digital nerve integrity.
      Local flaps usually do well in maintaining sensibility of the covered area in
      terms of two-point discrimination in contrast to split thickness skin grafts
      (STSG). Aim was to determine the frequency of sensory deficit in terms of Two
      Point Discrimination (TPD) in Split Thickness Skin Grafts (STSG) and local flaps
      for soft tissue defects of fingers three months postoperatively. METHODS: Thirty
      five patients underwent local flap coverage and other thirty-five had split
      thickness skin grafting for soft tissue defects of fingers depending upon nature
      of defect. Patients were followed up at 2, 4, 8 and 12 weeks. TPD, measured at 3
      months of follow-up, of 7 mm was considered normal (no sensory deficit) and TPD
      of 8 mm or more was considered as sensory deficit. RESULTS: The sensory deficit
      observed at the end of 12th week post operatively was 8.6% in the patients with
      local flap coverage (3 patients) and 45.7% with STSG (16 patients). Patients with
      no sensory deficit were 91.4% (32 patients) in the local flap coverage and 54.3%
      (19 patients) in the STSG at 12th week of follow up. The relative ratio (RR) of
      sensory deficit in local flaps and STSG was 5 (> 2). CONCLUSIONS: Local flaps are
      better options in terms of TPD preservation as opposed to STSG for soft tissue
      defects of fingers.

PMID- 23855106
TI  - Seasonal variations of vivax and falciparum malaria: an observation at a tertiary
      care hospital.
AB  - BACKGROUND: Malaria is a major public health problem in the malaria endemic zones
      of the world. Various factors influence the prevalence of malaria. This study was
      conducted to determine the variation in frequency of Plasmodium vivax and
      Plasmodium falciparum malaria in different seasons of the year in Khyber Teaching
      Hospital, Peshawar. METHODS: A total of 411 patients were included in the study.
      All these febrile patients were reported to have trophozoites of either
      Plasmodium vivax or Plasmodium falciparum malaria on Giemsa stained thick and
      thin smears. The frequency of vivax and falciparum malaria was worked out and
      statistically analysed for different season of the year. The study was carried
      out from 2nd Jan 2004 till 31st December 2008. RESULTS: Out of total 411
      diagnosed malaria cases, total 134 (32.60%) presented in the autumn season (vivax
      = 33.58%, and falciparum = 66.42%), 37 (9%) in winter season (vivax = 32.4%, and
      falciparum = 67.6%), 76 (18.49%) in spring season (vivax = 93.4% and falciparum
      6.6%) and 164 (39.90%) in summer season (vivax = 89.6, and falciparum = 10.4%).
      The malaria showed a highly significant pattern in different seasons of the year
      (p = 0.00) in a way that Plasmodium falciparum malaria reached its highest
      frequency in autumn and winter seasons while Plasmodium vivax malaria reached its
      peak frequency in spring and summer seasons. CONCLUSION: There was highly
      significant seasonal variation of vivax and falciparum malaria. There is arrival
      of Plasmodium falciparum in autumn which peaks in winter followed by arrival of
      Plasmodium vivax in spring till the end of summer.

PMID- 23855105
TI  - Impact of leiomyoma in pregnancy.
AB  - BACKGROUND: Uterine fibroids or leiomyomas are benign tumours that develop in the
      uterus, a female reproductive organ. These cause severe complications in females
      during pregnancy. This study was conducted to see the impact of leiomyoma in
      pregnant females to make decision for its management in future. METHODS: During
      one year of study, total 10,842 patients presented in CMH Lahore for antenatal
      check-up were included in the study. Out of them, 80 patients had leiomyoma in
      first trimester. They were followed during antenatal period. Maternal age,
      parity, size of fibroid, complications during pregnancy, labour and delivery,
      mode of delivery and indications of caesarean section were noted. RESULTS: The
      prevalence of fibroids (> or = 5 Cm) in pregnant females was 0.74%. The most
      common complication observed was PPH (31, 38.75%) cases. Miscarriage occurred in
      8 (10%) cases, cord prolepses was observed in 6 (7.5%) cases, placental abruption
      in 6 (7.5%) cases, placenta previa in 2 (2.5%) cases and retained placenta was
      observed in 1 (1.25%) case. Breech presentation was found in 10 (12.5%) cases and
      abdominal hysterectomy was done in 10 (12.5%) cases. Preterm labour occurred in 8
      (10%) cases and IUGR was present in 5 (6.25%) cases. No maternal was reported
      during the study. Among all females, 64 (80%) continue their pregnancy up to term
      (37-40 weeks of gestation), out of which vaginal delivery occurred in 19 (29.69%)
      while 45 (70.3%) had LSCS due to failure in progress in 17 (37.8%), cord
      prolapsed in 6 (13.3%) cases, fibroid in lower segment in 3 (6.7%) cases, breech
      presentation in 10 (22.2%) cases and low lying placenta in 2 (4.4%) cases.
      CONCLUSION: Pregnancy with fibroid is associated with increase in caesarean
      section rate especially due to dysfunctional labour and malpresentation. There is
      also increase in incidence of postpartum haemorrhage and associated hysterectomy.

PMID- 23855107
TI  - Perception of leadership among health managers working in tertiary level
      hospitals.
AB  - BACKGROUND: Rapid growth of medical knowledge has created major changes in
      technology which in turn has created greater demand of the client for better
      health services, and health sector is constantly under pressure of great internal
      and external demands. Quality of services, largely depend on to what extent
      managers are well versed with the concept of evidence based management, team and
      group approach in achieving organizational objectives. Making an effective health
      system, addressing the double burden of diseases coupled with resource crunch in
      developing countries is a big challenge for policy makers and health managers.
      Comprehensive concepts and application knowledge of leadership is very important
      for health managers in the present day in order to get best output that satisfies
      all the stake holders. Present anthropological study was done to assess the
      perception and knowledge of leadership among the health managers working in
      tertiary level hospitals. METHODS: This qualitative study was conducted in two
      public sector tertiary level hospitals of Lahore chosen randomly out of a total
      of seven such hospitals in the same city. Convenient sampling technique was used.
      Observation and in- depth interviews were conducted for data collection. Open
      ended questionnaire on the lines of MLQ was used. One main domain of leadership
      was developed and categorisation of the themes was done in the two evolved
      categories of transformational and transactional leadership. RESULTS: In the
      domain of leadership 10 of the health managers showed positive themes for
      transactional leadership, 6 showed positive themes for transformational
      leadership, and still 1 health manager showed overall negative response for the
      concept of leadership; he was totally in favour of dictatorship. CONCLUSION:
      Health managers with degrees in management/administration had better concept
      about the key idea of leadership and its variables. Female health managers were
      more inclined towards transformational leadership behaviour.

PMID- 23855108
TI  - Reasons for discontinuation of contraceptive methods among couples with different
      family size and educational status.
AB  - BACKGROUND: High rates of contraceptive discontinuation for reasons other than
      the desire for pregnancy are a public health concern because of their association
      with negative reproductive health outcomes. The objective of this study was to
      determine reasons for discontinuation of contraceptive methods among couples with
      different family size and educational status. METHODS: This cross-sectional study
      was carried out at the Obstetrics/Gynaecology Out-Patient Department of Pakistan
      Institute of Medical Sciences, Islamabad from April-September 2012. Patients
      (241) were selected by consecutive sampling after informed written consent and
      acquiring approval of Ethical Committee. The survey interview tool was a semi
      structured questionnaire. RESULTS: Majority (68%) of women belonged to urban, and
      the rest were from rural areas. Mean age of these women was 29.43 +/- 5.384 year.
      Reasons for discontinuation of contraceptives included fear of injectable
      contraceptives (2.9%), contraceptive failure/pregnancy (7.46%), desire to become
      pregnant (63.48%), husband away at job (2.49%), health concerns/side effects
      (16.18%), affordability (0.83%), inconvenient to use (1.24%), acceptability
      (0.83%) and accessibility/lack of information (4.56%). Association of different
      reasons of discontinuation (chi square test) with the family size (actual number
      of children) was significant (p = 0.019) but was not significant with husband's
      or wife's educational status (p = 0.33 and 0.285 respectively). CONCLUSIONS:
      Keeping in mind the complex socioeconomic conditions in our country, Family
      planning programmers and stake holders need to identify women who strongly want
      to avoid a pregnancy and finding ways to help the couples successfully initiate
      and maintain appropriate contraceptive use.

PMID- 23855109
TI  - Knowledge and perceptions of diabetes in urban and semi urban population of
      Peshawar, Pakistan.
AB  - BACKGROUND: Diabetes mellitus is a major health issue in Pakistan. The aim of
      this study was to evaluate the knowledge and perceptions of diabetes in a sample
      population of Peshawar. METHODS: This cross-sectional, descriptive study was
      carried out in seven different localities of Peshawar. A sample of 305 residents
      were interviewed aged from 15-60 years and above, using a questionnaire
      specifically designed and translated into Urdu language for convenience of
      selected subjects. RESULTS: Knowledge of diabetes was suboptimal. The mean
      percentages of correct responses to questions regarding three classical symptoms
      and given complications were 47.1% and 30.8%. Excessive sugar intake, obesity,
      family history, lack of physical activities and stress were acknowledged by
      46.2%, 42.3%, 39.3%, 33.4%, and 31.8% of the subjects respectively. Presence of
      family history and level of education were recognised to be associated with more
      knowledge. CONCLUSION: There is lack of awareness of major risk factors and some
      complications of diabetes mellitus. Level of education is a significant predictor
      regarding knowledge of diabetes and its prevention. Prevalence of diabetes has
      increased in Pakistan.

PMID- 23855110
TI  - How does self-efficacy affect performance of learner?
AB  - All types of attribution based on which learners make their judgement (i.e., self
      efficacy), about academic success or failure or about a specific task usually
      affect their performance and their capabilities to deal with different realities.
      It is perhaps the most distinctive capability of self-reflection. Many of the
      cognitive theorists have defined it as a meta-cognitive capability. This
      judgement influence learners choose what to do, how much effort to be invested in
      the activity, how long to carry the phase of disappointment, and whether to
      approach the task anxiously or with assurance.

PMID- 23855111
TI  - Apoptotic proteins and cancer: many faces.

PMID- 23855112
TI  - False positive HIV test in low prevalence region: Pakistan.
AB  - The prevalence of HIV in Pakistan is less than 0.1%, but is feared to be
      spreading among the general population rapidly. Screening tests for HIV is based
      on antibody detection. There seems to be little knowledge regarding the
      interpretation of HIV results among the population. Most often the patients are
      being issued a positive HIV report based on single screening test when in fact it
      should be confirmed before issuing a positive HIV result. There is a lot of
      stigma associated with the disease in Pakistan, on the other hand the test is
      done mostly without counselling services hence causing physical and mental trauma
      to the patients.

PMID- 23855113
TI  - Osseous metaplasia of endometrium--a rare cause of menometrorrhagia.
AB  - Osseous metaplasia is a rare disorder of endometrium in which a bone is formed
      from a different tissue inside the same individual. It is not generally
      applicable to the persistence of embryonic or foetal bone resulting in
      calcification or ossification. Most common presentation of osseous metaplasia of
      bone is infertility usually secondary. A case of osseous metaplasia as a cause of
      memetrorrhagia as a rare entity is presented.

PMID- 23855114
TI  - Primary alveolar proteinosis.
AB  - A 35 years old man presented with primary pulmonary alveolar proteinosis who was
      admitted to chest unit of ATH through casualty department. Before he came to our
      ward he was treated with different antibiotics including anti-tuberculosis drugs
      for a month at least. But his symptoms did not improve rather his dyspnoea got
      worse. He was misdiagnosed till histopathology revealed that he has pulmonary
      alveolar proteinosis. With this background we briefly review clinical features,
      diagnosis and treatment of this rare disease.

PMID- 23855115
TI  - An analysis of intestinal parasitic infestation in Dera Ismail Khan, Pakistan.

PMID- 23855116
TI  - [Accessing the features of surface neuraminidase (N1) of influenza A virus
      presenting on the platforms for anti-NA Abs screening].
AB  - OBJECTIVE: To understand if the Neuraminidase (N1) of Influenza A virus at the
      surface of yeast-displaying system, eukaryotic expression system and the infected
      cells could be used for anti-NA Abs screening, their activities and bindings to
      five candidate Abs were assayed. METHODS: The surface NA expression was obtained
      by transfecting by recombinant NA constructors with specific tag-labels or live
      virus infection. The functional activity was measured by the fluorescent assay.
      Their bindings to the Abs were detected by flow cytometry. RESULTS: The surface
      NAs presenting on the yeast-displaying system and eukaryotic expression system
      exhibited functional NA activities as the NA at the surface of virus-infected
      cells which showed affinities to Ab1, 4, and 5. The same bindings to Abl and 5
      were found in the surface NA expressed by eukaryotic expression system while
      minor binding was observed in the yeast displayed-NA. CONCLUSION: The epitopes of
      yeast-displayed NA may be different from the NAs present at eukaryotic expression
      system and the infected cells which more likely suitable for the screening of
      anti-NA Abs.

PMID- 23855117
TI  - [Expression of NA of influenza virus and C3d fusion gene in replication-defective
      recombinant adenovirus and its immune efficacy analysis].
AB  - OBJECTIVE: To construct a replication-defective recombinant adenovirus expressing
      the fusion gene of neuraminidase (NA) gene in influenza virus A/FM/1/47 and C3d
      and to evaluate the induced immune efficacy. METHODS: NA-C3d was cloned into
      shutter vector pAdTrack-CMV, which was cotransformated with adenovirus DNA into
      E. coli BJ5183. The recombinant adenovirus genomic DNA was generated through
      homological recombination. The recombinant adenovirus was produced by
      transfecting 293 cell line with the genomic DNA and the induced immune efficacy
      in mice were analyzed. RESULTS: The integration of NA-C3d in the adenovirus
      genomic DNA and its expression were confirmed by PCR and Western-Blot assays
      respectively. After intranasal immunization, the serum IgG was induced at a titer
      of 1: 1000 and 1:100 000 in BALB/c mice at primary and secondary immunization
      respectively. The vaccinated mice were completely survived when challenged with
      wide influenza virus. CONCLUSION: recombinant adenovirus expressing NA-C3d was
      successfully constructed and it could induce desired immune efficacy.

PMID- 23855118
TI  - [Analysis the viral etiology of fever and respiratory tract infection syndrome in
      Shaanxi province].
AB  - OBJECTIVE: Analysis the viral pathogenic spectrum for patients with fever and
      respiratory tract infection syndrome in Shaanxi province during 2010 and
      investigate the molecular epidemiology characteristics of respiratory syncytial
      virus. METHODS: A total of 208 patients' pharyngeal swabs were collected based on
      surveillance definition from January 2010 to January 2011 and screened for
      sixteen human respiratory virus types/subtypes by Qiaxcel-based multiplex reverse
      transcription-PCR assay, including HRV,HCoV, Flu, HPIV, ADV, HRSV, HMPV and HBoV
      and investigate molecular epidemiology of HRSV by sequencing and phylogenetic
      analysis of the C-terminal second hypervariable region of the G gene. RESULTS:
      109 out of 208 specimens (53%) were positive for one or more viruses. HRSV(42.
      2%) was the dominant pathogen detected, followed by Flu(24. 5%), PIV(20%),
      HRV(13.6%) and ADV( 10.9%),there were also 8 strains of HCoV, 5 strains of HMPV
      and 3 strains of HBoV detected. The results showed that 22 specimens were
      positive for two or more viruses, PIV (14/22) was the most frequently detected
      viral agent among co-infection specimens, and the highest incidence of mixed
      infection is aged 15-39 years group (P < 0.05). The overall viral detection rate
      was no related to age. In addition to Flu, HMPV and PIV, other viruses (HRV,
      HBoV, HCoV, ADV, RSV) mainly infected 0 to 4 years old children. Among 46 HRSV
      positive specimens, 42 HRSV-A strains clustered into NA1 genotype and two HRSV-B
      strains clustered into two genotypes, BA9 and GB2. CONCLUSION: HRSV is the
      dominate pathogen collected from patients with fever and respiratory tract
      infection syndrome in Shaanxi and HRSV A is the predominant subtype. For most
      viruses, infection was most prevalent among children aged <4 years. PIV was the
      most common pathogen in co-infection.

PMID- 23855119
TI  - [2009 evolution for VP4 of enterovirus 71 strains in Shenzhen].
AB  - OBJECTIVE: To analyze the genetic evolution for the common causative agent of
      hand, foot and mouth disease(HFMD) that VP4 of human enterovirus 71 in Shenzhen
      district. METHOD: 491 sttol specimen were collected from, children with hand,
      foot and mouth diease in Shenzhen Children's Hospital 2009. After cell culture,
      VP4 gene of eight EV71 strains were amplified by reverse-transcriptase PCR( RT
      PCR), phylogenetic analysis of the VP4 gene was constructed by using MEGA 4. 0.
      RESULT: The VP4 gene of eight EV71 strains encoding 69 amino acids with full
      length 207 bp. The nucleotide homology of VP4 gene among eight EV71 strains was
      94. 2% -98. 1%, compared with VP4 gene of EV71 strains retrieved from Shenzhen
      2001 to 2004 and GenBank was 89. 1%-98. 1% and 79.2%-100% respectively. Asian
      epidemic strain Fuyang had the highest nucleotide homology, representative strain
      C4 and Shenzhen strain (AY895144) with 94. 2% -98. 1% secondly. Except for the
      54th amino acid of VP4 gene of India reported strain and one of the eight EV71
      strains, the homology of the rest amino acids between the eight EV71 strains and
      those in GenBank was 100%. Compared with representative strain C4,there were
      seventeen differences in nucleotide sequences of VP4 of the eight EV71 strains.
      All of the different nucleotides were located at the degenerate password sites
      except one. There was no significant difference in VP4 gene between the severe
      and the mild cases of strainS. The eight Shenzhen EV71 strains were classified as
      sub-genotype C4 in the phylogenetic tree. CONCLUSIONS: The epidemic of EV71 in
      Shenzhen 2009 was sub-genotype C4. VP4 gene of EV71 was very conservative which
      dose not belong to the variation section. The variation of most of nucleotide was
      invalid variation. The amino acids encoded by VP4 gene which variation was almost
      zero.

PMID- 23855120
TI  - [Study on BALB/c mice with EV71 infection by diverse inoculation routes].
AB  - OBJECTIVE: To study the characteristics of EV71 JN200804 strain infection in one
      day old BALBI c mjce and to establish a animal model of EV71 infection , and to
      provide information and technical support for the evaluation of the EV71 vaccine
      and antiviral medicine. METHODS: One-day old BALBic mice were infected with EV71
      JN200804 strain through oral( PO) ,intracranial(IC) ,intraperitoneal (IP),
      intramuscular (IM) routes, respectively. All mice were sacrificed at paralysis of
      hind limbs and collected organs for viral isolation, RT -PCR and pathological
      examination, and the electrophysiology were detected before sacrifice. RESULTS:
      All mice infected through IC, IP and IM routes were paralyzed in hind limbs at 4
      5 days and died at 7 days about, the hypokinesia and lethargy of mice were
      observed through PO routes. The viruses could be isolated and detected in the
      muscle from mice infected through IC, IP and IM routes and in the spinal cord
      through IC routes by viral isolation and RT-PCR. The neurogenic and myogenic
      disorders were detected by electromyography. Histopathologically, the varied
      pathologic changes were observed in the mouse cerebellum , spinal cord , muscle ,
      heart, lung, liver and kidney. CONCLUSION: EV71 JN200804 strain can infect one
      day old BALBI c mice and induce paralysis of hind limbs, its animal infection
      model may apply to study of EV71 infection pathogenesis and antiviral medicine,
      and evaluation of the EV71 vaccine.

PMID- 23855121
TI  - [Analysis of genetic diversity of HIV-1 nef genes from a patient with AIDS
      dementia complex].
AB  - OBJECTIVE: To study the genetic diversity of HIV-1 nef genes from a patient with
      AIDS dementia complex(ADC) , so as to research the amino acid variability and the
      pathogenesis of ADC. METHODS: The nef gene was amplified with PCR from genomic
      DNA which was extracted from spleen and different brain tissues(basal ganglia,
      frontal gray matter, meninges, temporal lobe)of a patient who died of ADC. PCR
      products were cloned into the pMD19-T vector, after transformation and selection
      by ampicillin and blue/white spotting. Five of positive clones were sequenced and
      confirmed with BLAST. HIV-1 nef sequences were processed with BioEdit and MEGA4
      to do Neighbor-Joining tree, p-Distances, and values of ds/dn. RESULTS: The
      samples were all identified as HIV-1 B and genetic variation exists in HIV-1 nef
      gene isolated from different tissues compared with HXB2. In addition,part of the
      changes were different between periphery and brain. CONCLUSION: Variations exist
      in the HIV-1 nef gene extracted from the ADC patient and the variations from
      peripheral and central nerve tissues were different,these variations may change
      the function of Nef,and it needs more research.

PMID- 23855122
TI  - [Analysis of the human papillomavirus in laryngeal squamous cell carcinoma
      patients].
AB  - OBJECTIVE: To analyze the infection of human papillomavirus in laryngeal squamous
      cell carcinoma patients. METHODS: The pathological samples of 64 clinical
      diagnosed laryngeal squamous cell carcinoma patients were collected. Lunimex and
      PCR techniques were used to detect the HPV gene infection and
      immunohistochemistry method was used to analyze the HPV protein expression in the
      samples. RESULTS: In the 64 cases, 7 were positive for HPV infection by Luminex
      and PCR tests. 18 were positive for HPV16/18 E6 protein expression. The total
      positive rate was about 39. 1%. CONCLUSION: The high HPV infection rate in
      laryngeal squamous cell carcinoma patients in the study indicated indirectly that
      the importance of the HPV infection in pathogenesis of the laryngeal squamous
      cell carcinoma.

PMID- 23855123
TI  - [Analysis on genetic characteristics of mumps virus strains circulating in Hunan
      province in 2011].
AB  - OBJECTIVE: To be acquainted with genetic characteristics and variation of mumps
      virus strains circulating in Hunan province. METHODS: Mumps virus (MV) strains
      were isolated using Vero/ SLAM cells. The small hydrophobic protein (SH) genes of
      MV isolates were sequenced, and the sequences were analysed phylogenetically
      between the isolated strains and other reference mumps strains. RESULTS: 4 mumps
      virus strains were isolated from 16 specimens collected in 2011 from different
      regions of Hunan province. The genotype of isolated strains were supposed to be F
      type. CONCLUSION: Genotype F is the main genotype of circulating strains in Hunan
      province in 2011 and there is no variation between genotype.

PMID- 23855124
TI  - [High-throughout detection and analysis of drug-resistance gene mutation for 2465
      cases with chronic hepatitis B in Shenzhen].
AB  - OBJECTIVE: To analyze the character of drug-resistance gene mutation for patients
      with chronic hepatitis B in Shenzhen. METHODS: 2465 clinical cases with chronic
      hepatitis B were analyzed for gene mutation with MALDI-TOF-MS in order to know
      about the epidemiology of HBV drug resistance and its clinical significance.
      RESULTS: 763 cases were detected mutation among the 2465 cases. The frequency of
      Lamivudine related mutation was the highest (42.96%), especially on rtL180M (14.
      72%), rtL204I (18. 50%), rtL204V (9. 74%). The frequency of Adefovir related
      mutation was about 8. 19% , among of which rtN236T was 4. 15%. The frequency of
      Entecavir related mutation was about 0. 49%. Among all samples, rtS202I mutation
      couldn't be detected. The existence of drug resistance could be detected earlier
      with MALDI-TOF-MS from the results of dynamic follow-up. CONCLUSION: In Shenzhen,
      the main HBV mutation was associated with lamivudine and adefovir,and with lower
      frequency of mutation for entecavir,so the optimized treatment for HBV was
      entecavir. It could detect the existence of drug resistance effectively with
      MALDI-TOF-MS and guide clinical treatment.

PMID- 23855125
TI  - [Changes and analysis of peripheral white blood cells and lymphocyte subsets for
      patients with influenza B virus infection].
AB  - OBJECTIVE: To investigate the characters and changes of peripheral white blood
      cells and lymphocyte subsets of patients with influenza B virus infection and to
      provide evidences for diagnosis, treatment and prognosis of influenza B virus
      infection. METHODS: Peripheral white blood cell parameters and the percentages of
      lymphocyte subsets in acute and recovery phases of 47 cases of influenza B virus
      infection patients(32 mild cases and 15 severe cases)were investigated and
      analyzed,and compared respectively with those of 38 cases of healthy people using
      whole blood cell analysis and flow cytometry. RESULTS: Peripheral white blood
      cell counts of mild cases decreased greatly but peripheral white blood cell
      counts and the neutrophils of severe cases increased significantly in acute
      phase; the peripheral lymphocytes, CD3, CD4, CD8 and CD19 of all patients with
      influenza B virus infection decreased greatly in acute phase and quickly
      recovered in recovery phase;there were similar characteristics of change in NK
      cells between patients with influenza B virus and healthy people. NK cells
      absolute counts of severe cases decreased significantly in acute phase.
      CONCLUSION: Peripheral white blood cell counts and the neutrophils of increased
      significantly in acute phase and the great decrease of NK cells absolute counts
      of patients with influenza B virus infection may suggest the severe tendency of
      diseases.

PMID- 23855126
TI  - [Inhibition of hepatitis C virus replication by mycophenolic acid in
      hepatocytes].
AB  - OBJECTIVE: It is well known that cyclosporine A (CsA), a widely used
      immunosuppressant for clinical organ transplantation, has the ability to inhibit
      HCV replication. In this study, the effects of several other immunosuppressants,
      including mycophenolic acid (MPA), rapamycin and FK-506, on HCV replication were
      examined in human hepatocytes. METHODS: HCV JFH-l-infected hepatocytes were
      treated with immunosuppressants or with control vehicles. The levels of viral RNA
      and the expression of HCV core protein were determined by quantitative real-time
      RT-PCR and Western Blot assay, respectively. RESULTS: MPA-treated cells showed
      significant decreases in both viral RNA and HCV Core protein expression compared
      with the control cells. Moreover, MPA treatments of hepatocytes before, during or
      after HCV infection could significantly inhibit viral replication. In contrast,
      rapamycin and FK-506 had little effect on HCV replication. Mechanism research
      disclosed that the inhibition of HCV replication by MPA was mainly due to its
      depletion of guanosine, a purine nucleoside crucial for synthesis of guanosine
      triphosphate (GTP), which is required for initiation of HCV RNA replication. The
      supplement of exogenous guanosine could reverse most of anti-HCV effect of MPA.
      CONCLUSION: These results indicate that MPA, through the depletion of guanosine,
      inhibits HCV JFH-1 replication in hepatocytes, suggesting that MPA may be
      beneficial for HCV-infected transplant recipients.

PMID- 23855127
TI  - [The preliminary study of HBV genotype distribution and the relationship with
      clinical manifestation].
AB  - OBJECTIVE: To explore the relationship between HBV genotypes distribution in
      hepatitis B patients and clinical manifestations in Beijing area. METHODS: 200
      HBsAg positive serum were choosen from 1148 serum samples. useing of nested PCR
      amplification method, HBV DNA S genes were Sequencing and typing; genotype
      distribution and the relationship with the clinical manifestation were
      Statistical analysis. RESULTS: In Beijing area, HBV has B, C, D three genotypes,
      including B gene type 17 cases (12. 5%), C genotype 116 cases (85.2%), D genotype
      3 cases (0.02%); in the carriers, patients with chronic hepatitis B, cirrhosis,
      liver cancer, B type have been gradually falling, C type have been gradually
      rising trend. CONCLUSION: Serious liver disease relate with C type, B type
      patients with HBV infection is better than C type patients in clinical prognosis
      and antivirus treatment response.

PMID- 23855128
TI  - [Clinical situation and analysis on the detection result of HIV antibody in
      Shandong province from 2003 to 2011].
AB  - OBJECTIVE: To provide the basis for clinical acquired immunodeficiency syndrome
      (AIDS) surveillance and to avoid cross infection in hospital, we study the
      infection status of AIDS in Shandong province. METHODS: The fourth-generated
      Akzo's ELISA kit and the fourth generated Immunoluminometric detection reagent
      were used for HIV antibody screening for 399 303 cases of both inpatients and
      outpatients from Jan. 2003 to Dec. 2011. Beijing WanTai ELISA kit and Se-marked
      rapid detection reagent were used for re-detection, and the positive samples were
      sent to the local CDC for confirming test by Western Blot. RESULTS: The HIV-1
      antibody detection results of 129 (0. 3230 per thousand) patients were confirmed
      to be positive, including 54 (0. 1352 per thousand) cases of outpatients and 75
      (0. 1878 per thousand) cases of inpatients. HIV infection rates in outpatients
      from 2003 to 2011 were 0.050 per thousand, 0.030 per thousand, 0.111 per
      thousand, 0.120 per thousand, 0.124 per thousand, 0.113 per thousand, 0.148 per
      thousand, 0.201 per thousand, 0.2152 per thousand; and that in inpatients were 0.
      150 per thousand, 0.089 per thousand, 0.138 per thousand, 0. 144 per thousand, 0.
      104 per thousand, 0. 132 per thousand, 0. 197 per thousand, 0. 329 per thousand,
      0. 313 per thousand respectively. Among these inpatients, there were 61 cases of
      medical patients and 14 cases of surgical patients, and most were youths and
      farmers. CONCLUSIONS: HIV infection rate was increasing year by year. Most
      inpatients whose HIV-1 antibody was positive were in the phase of AIDS.
      Therefore, it's very necessary to execute routine testing for inpatients and
      outpatients who need special examination for early diagnosis of HIV infection

PMID- 23855129
TI  - [Clinical research of the relation of hepatitis B surface antigen (HBsAg)
      quantification and hepatic tissue pathological staging].
AB  - OBJECTIVE: To explore the correlation of serum hepatitis B surface antigen
      (HBsAg) level and hepatic tissue pathological staging in the chronic hepatitis B
      infected persons. METHODS: Collect the clinical data of 272 cases who are HBsAg
      positive more than 6 months and accepted hepatic biopsy in our hospital. Detect
      serum HBsAg quantification, ALT, HBV DNA, complete blood count, hepatic tissue
      pathological staging, grouping the cases according to the stage of inflammation
      and the fibrosis degree respectively. Observe serum HBsAg quantification, HBV DNA
      and the stage of inflammation and the fibrosis degree. Analyse the correlation
      between HBsAg quantification and HBV DNA. RESULTS: The correlation of serum HBsAg
      level and HBV DNA is notable. Serum HBsAg level is a variable affecting hepatic
      tissue pathological stage significantly. CONCLUSIONS: Serum HBsAg level is a
      marker having higher specificity and sensitivity to diagnose the hepatic
      fibrosis.

PMID- 23855130
TI  - [Oxidative stress in chronic hepatitis C patients].
AB  - OBJECTIVE: This study is aimed to investigate oxidative stress status in chronic
      hepatitis C (CHC) patients. METHODS: 52 CHC patients were divided into two groups
      according to the serum level of alanine aminotransferase (ALT): group A (elevated
      ALT group) and group B (normal ALT group). 20 healthy controls were included in
      this study. Serum levels of xanthine oxidase (XOD), malondialdehyde (MDA),
      oxidizided glutathione (GSSG), glutathione (GSH), glutathione peroxidase (GSH
      Px), glutathione S-transferase (GST), glutathione reductase (GR) and vitamin C
      (Vc) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum
      levels of XOD, MDA, GST and GR increased in CHC patients compared with healthy
      controls. While, serum levels of GSH, GSH-Px and Vc decreased compared with
      healthy controls. Furthermore, serum levels of XOD, MDA, GSSG, GST and GR in
      group A were up-regulated compared with group B. Serum levels of GSH, GSH-Px and
      Vc in group A were down-regulated compared with group B. In CHC patients, serum
      ALT level positively correlated with serum levels of XOD, MDA, GSSG and GST,
      while, negatively correlated with serum levels of GSH, GSH-Px and Vc. Serum
      aspartate aminotransferase (AST) level positively correlated with serum levels of
      XOD, MDA, GSSG, GR and GST, while, negatively correlated with serum GSH-Px level
      in CHC patients. Serum gamma-glutamyl transpeptidase (GGT) level positively
      correlated with serum GR level and negatively correlated with serum GSH level in
      CHC patients. Serum alkaline phosphatase (AKP) level positively correlated with
      serum levels of MDA and GR in CHC patients. In CHC patients, serum XOD level was
      positively related with serum HCV RNA level. CONCLUSION: Oxidative stress was
      increased in CHC patients. In CHC patients with elevated serum ALT level,
      oxidative stress usually became serious.

PMID- 23855131
TI  - [Influence of non-sodium restricted diet with diuretics on plasma rennin, renal
      blood flow and in patients with cirrhotic ascites].
AB  - OBJECTIVE: To explore influence of sodium restricted diet and non-sodium
      restricted diet on plasma rennin (PRA), angiotensin II (All), ALD, renal blood
      flow (RBF) and subside of ascites in patients with cirrhotic ascites. METHODS:
      Eighty cases of hepatitis B with cirrhotic ascites were randomly divided into
      sodium restricted diet group and non-sodium restricted diet group. 39 cases were
      in non-sodium restricted diet group, taking sodium chloride 6500-8000 mg daily;
      41 cases were in sodium restricted diet group, taking sodium chloride 5000 mg
      daily. Both groups received diuretics furosemide and spironolactone. Blood
      sodium, urine sodium, PRA, AII, ALD, RBF ascites subsiding were compared after
      treatment. RESULTS: In non-sodium restricted diet group, blood sodium and urine
      sodium increased 10 days after treatment compared with those before treatment,
      and compared with those of sodium restricted diet group 10 days after treatment,
      P <0. 01. RBF increased compared with that before treatment, and compared with
      that of sodium restricted diet group 10 days after treatment, P < 0. 01. Renal
      damage induced by low blood sodium after treatment was less in non-sodium
      restricted diet group than that in sodium restricted diet group, P <0. 05.
      Ascites disappearance upon discharge was more in sodium restricted diet group
      than that in non-sodium restricted diet group, P <0. 01. Time of ascites
      disappearance was shorter in non-sodium restricted diet group than that in sodium
      restricted diet group, P < 0. 01. CONCLUSION: Compared with sodium restricted
      diet, while using diuretics of both groups, non-sodium restricted diet can
      increase level of blood sodium, thus increasing excretion of urine sodium and
      diuretic effect. It can also decrease levels of PRA, AII and ALD, increase renal
      blood flow and prevent renal damage induced by low blood sodium and facilitate
      subsiding of ascites.

PMID- 23855132
TI  - [Detected of associated contagious parameters of blood recipients before
      transfusion and their clinical significance].
AB  - OBJECTIVE: To investigate the significance in prevention of nosocomial infection
      of the testing of the associated contagious parameters of blood recipients before
      transfusion. METHODS: A retrospective analysis was adopted, 44 968 pre
      transfusion patients were tested the serum hepatitis B virus surface antigen
      (HBsAg), antibody against hepatitis C virus (anti-HCV), antibody against T.
      pallidum (anti-TP) and antibody against human immunodeficiency virus(anti-HIV).
      RESULTS: The total positive rate was 22.41%. Positive rate of HBsAg, anti-HCV and
      anti-TP were 20. 67% (9294/44 968) , 0.33% (148/ 44 968) and 1.65% (9741/44968),
      respectively; anti-HIV was positive in 39 patients, 23 cases coinfection of the
      other three indicators at least one positive in 39 cases of anti-HIV-positive
      blood recipients, of which was mostly observed T. pallidum; co-infection of HBV,
      HCV and/or TP were 117 cases, and were mostly observed between HBV and HCV, HCV
      and TP; for HBV infection the department of digestive medicine was
      prevalent(Chi2>or=83.0, P <0.01). CONCLUSION: Part of blood recipients before
      admission had been infected with a contagious disease. The testing of the
      associated contagious parameters of blood recipients before transfusion is not
      only useful for both of the hospital and the patients, but also more important to
      ensure safe blood transfusion, decrease medial dissatisfaction and to prevent
      nosocomial infection.

PMID- 23855133
TI  - [Analysis of death causes of 345 cases with HIV/AIDS in Guangdong area].
AB  - OBJECTIVE: To analyze the death causes of 345 cases with HIV/AIDS in Guangdong
      area. METHODS: The situations of 345 hospitalized death cases with HIV/AIDS were
      conducted by retrospective analysis. RESULTS: (1)There were total 3406
      hospitalized cases with HIV/AIDS in a hospital from January 2001 to December 2011
      and 345 cases died, the fatality rate was 10. 13%. Since 2005 the introduction of
      free anti-viral treatment, the fatality rate of HIV/AIDS declined. The fatality
      rate of the patients whose CD4+ T lymphocyte counts <200 cells/microl was 14.61%
      (299/2046) and it was significantly higher than that of patients whose CD4 T
      lymphocyte counts >or=200 cells/microl (P <0.01). (2) 99.42% of the death cases
      had more than one kind of opportunistic infections (OI) and there were 924 cases
      of OI totally. 84. 64% of OI related to the death directly. Fungal infection was
      the most common in OI, followed by bacterial infection. Most OI occurred in the
      lungs, mouth, other systemic disseminated diseases, gastrointestine, central
      nerver system, septicemia, skin. The AIDS defining opportunistic infections such
      as several pneumonia, disseminated penicilliosis marneffei and CNS infections
      accounted for 29.65%. Other factors that caused HIV/AIDS death included
      opportunistic tumors, HIV related disease and non AIDS-related disease accounted
      for 15.36%. No accepted effective highly active antiretroviral therapy (HARRT)
      also constituted factors of death. Among cases which accepted HARRT treatment,
      only 6.96% had the period of treatment over three months. CONCLUSION: The
      fatality rate of end-stage AIDS patients was high and the opportunistic
      infections was the most important cause of death. Early diagnosis and treatment
      for opportunistic infections, timely effective HARRT were the key to improve the
      quality of life of AIDS patients.

PMID- 23855134
TI  - [The studies on clinical value of AFP-L3 detected by microspincolum method for
      judgment of treatment response in patients with HCC undergoing TACE].
AB  - OBJECTIVE: To explore the clinical value of Lens culinaris agglutinin-reactive
      alpha-fetoprotein detected by microspincolum method for judgment of treatment
      response in patients with hepatocellular carcinoma undergoing transcatheter
      arterial chemoembolization. METHODS: Twenty eight patients with HCC undergoing
      TACE follow-up in hospital were recruited. AFP and AFP-L3 were measured in all
      the patients before and after TACE, and correlations were analyzed between AFP
      L3% and response to treatment. RESULTS: Among the twenty eight patients with HCC
      undergoing TACE, 8 out 11 case in AFP-L3% descent group had well treatment
      response, 5 out 17 case in AFP-L3% elevated group had well treatment
      response(Chi2 = 4. 858, P < 0. 05). CONCLUSIONS: The detection of AFP-L3 by
      microspincolum method is useful to judgment of treatment response in patients
      with HCC undergoing TACE.

PMID- 23855135
TI  - [The investigantion of comparative experiments for different clinical laboratory
      instruments].
AB  - OBJECTIVE: To estimate the consistency of two VITROS 3600 chemiluminescent
      analyzers according to the requirement of ISO15189. METHODS: Verification tests
      were made for precision and accuracy of anti-HCV in two instruments. While 40
      serum samples including Anti-HCV negative (10 cases) , positive (10 cases) , and
      weakly positive (20 cases). and the test results were statistical analised.
      RESULTS: Two instruments negative and positive control samples intra-batch
      precision and coefficients of variation were 5% , 4% and 7. 14% , 7. 23% , inter
      batch precision and coefficients of variation were 9. 47% , 7. 7% and 8.04%, 7.
      6%, are less than requirement CV (15%) by ISO15189. The accuracy of two
      instrument were 100% , The test results of the control samples showed no
      significant difference (P < 0. 05). The correlation analysis of the test results
      of clinical samples R2 =0. 9984, with good consistency. CONCLUSION: Test results
      of two Vitros 3600 has good consistency and comparability.

PMID- 23855136
TI  - [A protein array based on quantum dots (QDs) encoded microbeads for detection of
      hepatitis C virus].
AB  - OBJECTIVE: To establish a hepatitis C virus (HCV) diagnostic assay using a
      protein array based on the quantum dots (QDs) encoded microbeads. METHOD: Using
      QDs encoded microbeads array and immunofluorescence techniques, the highly
      purified HCV NS3, NS4, NS5 and Core protein were respectively immobilized on the
      surface of encoded beads, which were used for the detection of anti-HCV antibody
      in serum. To evaluate the microbeads protein array, 120 HCV positive and 50 HCV
      negative samples were tested, and compared with recombinant immunoblot
      assay(RIBA) results as golden standard. The sensitivity, specificity and accuracy
      value were calculated. RESULTS: Compared 120 positive samples detected with RIBA,
      the sensitivity of microbeads array is 97.50% (117/120), the specificity is 96.0%
      (48/50), and accuracy is 97. 06% [(117 + 48)/(120 + 50)], The sensitivity of
      microbeads protein array is similar with RIBA methods. In the 120 positive
      samples tested with protein array, the positive rate of anti-HCV Core is 92. 50%
      (111/120) , the positive rate of anti-HCV NS3 is 89. 17% (107/120), the positive
      rate of anti-HCV NS4 is 70. 83% (85/120), the positive rate of anti-HCV NS5 is
      52.50% (63/120).

PMID- 23855137
TI  - [Evaluation of specific antibodies of blood receiver sera to Treponema pallidum
      by chemiluminescence immunoassay].
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance
      of chemiluminescence immunoassay (CLIA ) , in comparison with that of the
      following currently used treponemal tests: hemagglutination test (TPHA), and
      Western Blot (WB). METHODS: First, a retrospective study was performed with a
      panel of 18 494 blood receiver sera by CLIA and TPHA, the specific antibody
      against T. pallidum in 177 were positive sera by CLIA and/or TPHA, 81 clinical
      and serologically characterized syphilitic sera, 55 sera obtained from subjects
      with potentially interfering diseases, and 250 healthy sera were negative were
      detected by CLIA, TPHA and WB. RESULTS: The results of WB as the gold standard,
      the sensitivity of CLIA (98. 4%) was significantly higher than that of TPHA (94.
      4%) (Chi2 = 5.76,P <0. 05), the specificity of CLIA (100%) was similar to that of
      TPHA (99.7%) (Chi2 =1. 0, P >0. 05). CONCLUSION: CLIA is characterized with
      higher sensitivity and specificity, It is suitable for screening Syphilis in
      clinical laboratory.

PMID- 23855138
TI  - [Analysis on status and characteristics of laboratory-acquired vaccinia virus
      infections cases].
AB  - OBJECTIVE: By analyzing the status and characteristics of vaccinia virus
      laboratory-acquired infections in the bibliographical information, this paper
      provides relevant recommendations and measures for prevention and control of
      vaccinia virus laboratory-acquired infections in China. METHODS: Choosing PubMed,
      Embase, Biosis and SCIE, SSCI, CPCI-S as well as CPCI-SSH covered by Web of
      Science as the data source, indexing the bibliography of vaccinia virus
      laboratory-acquired infections, this paper analyzes the information on whether to
      vaccinate, the occurrence time of symptoms, diseasedparts, symptom
      characteristics and the disease-causing reasons. RESULTS: The outcome shows that
      52. 9% of the cases never get vaccinated, 82.4% engaged in vaccinia virus related
      researches never get vaccinated in 10 years, 52. 9% get infected by the
      accidental needlestick in hands during the process of handling animal
      experiments, 70. 6% of infections occur in the hands and having symptoms after
      being exposed with an average of 5. 1 days. CONCLUSION: Although it is still
      controversial that whether or not to be vaccinated before carrying out vaccinia
      virus related works, it should be important aspects of prevention and control of
      vaccinia virus laboratory-acquired infections with the strict compliance with the
      operating requirements of the biosafety, by strengthening personal protection and
      timely taking emergency measures when unforeseen circumstances occur, as well as
      providing the research background information to doctors.

PMID- 23855139
TI  - Why a fluid manager makes sense in your dialysis clinic.

PMID- 23855140
TI  - Management of anemia in patients with kidney disease in 2013 and beyond.

PMID- 23855141
TI  - ESA dose vs. Hb levels: what needs to be monitored?

PMID- 23855143
TI  - Choice of erythropoiesis stimulating agent in ESRD.

PMID- 23855142
TI  - ESAs and irons in the pipeline: how do they differ?

PMID- 23855144
TI  - Is allosensitization a strong enough reason to avoid transfusions?

PMID- 23855145
TI  - Is eliminating the floor for the Hb range consistent with patient-centered care?

PMID- 23855146
TI  - How do we operationalize the individualization of ESA dosing and target Hb
      levels?

PMID- 23855147
TI  - Anemia management using computerized decision support.

PMID- 23855148
TI  - Protein links CV disease with type 1 diabetes.

PMID- 23855149
TI  - Persistent hyperkalemia? Maybe it's the Noni juice, not the orange juice.

PMID- 23855150
TI  - Managing a dialysis clinic: the ever-changing landscape.

PMID- 23855151
TI  - NMC given new powers to speed up fitness to practise procedures.

PMID- 23855152
TI  - Poll reveals that NHS staff think employers sacrifice care quality.

PMID- 23855153
TI  - New guidance will steer decisions on staffing levels, says Welsh CNO.

PMID- 23855154
TI  - Is this year's increase in training places a positive sign or just a blip?

PMID- 23855155
TI  - Hear our voice.
AB  - Founded half a century ago by a teacher upset at the way her husband was treated
      in hospital, the Patients Association has become a campaigning force, influencing
      attitudes to patient involvement in health care. Patients have more say today,
      but meaningful engagement in services is still uncommon.

PMID- 23855157
TI  - A positive drain on the system.
AB  - Established in pilot form five years ago, an innovative nurse-led paracentesis
      service at the Christie Hospital in Manchester has reduced waiting times,
      improved patient satisfaction, and saved the trust pound 250,000 a year.

PMID- 23855156
TI  - Vision for a brighter future.
AB  - Nurses at Moorfields Eye Hospital in London are taking on more autonomous roles,
      performing surgery and supporting patients from admission to discharge. A new
      strategy has been designed to make the hospital a nationally recognised provider
      of ophthalmic nurse education.

PMID- 23855158
TI  - Developing a community mental health nursing handover form.
AB  - While nursing handovers are predominantly used in ward settings, this essential
      form of communication is also used by community mental health teams to promote
      continuity of care. A community mental health nursing handover form was developed
      to overcome poor communication of patient information. It is expected that the
      form will increase efficiency and reduce handover time by focusing on pertinent
      and current patient information. Implementation of a community mental health
      nursing handover form requires the willingness of staff to be proactive and
      embrace change. The involvement of nurse leaders is essential to implement
      successful change, overcome barriers and motivate staff.

PMID- 23855159
TI  - Hepatitis E virus infection.
AB  - Hepatitis resulting from viral infection is common worldwide and is associated
      with significant morbidity and mortality. Caused by a group of unrelated viruses
      that target the liver, hepatitis E virus is not well understood and is
      consequently often perceived in many countries as unimportant. This article
      describes the main features of hepatitis E virus and reviews global patterns of
      transmission, endemicity and the variable clinical outcomes of infection,
      especially in pregnant women and anyone who is immunocompromised. Infection
      prevention measures are also discussed.

PMID- 23855161
TI  - Mentoring students.

PMID- 23855160
TI  - Use of statins to reduce the risk of cardiovascular disease in adults.
AB  - The relationship between serum cholesterol and cardiovascular disease is well
      established. Primary and secondary prevention of cardiovascular events involves
      the use of statins to reduce cholesterol levels, as recommended by the National
      Institute for Health and Care Excellence. This article provides an overview of
      fats and lipids within the body, and explores how statins work to reduce
      cholesterol. The risks and benefits of statin therapy are discussed, including
      food and drug interactions, and optimum dose time.

PMID- 23855162
TI  - All change for nursing.

PMID- 23855163
TI  - A lesson in how to educate staff.

PMID- 23855164
TI  - Learning from experience.

PMID- 23855165
TI  - Revascularization/Regeneration performed in immature molars: case reports.
AB  - These 3 case reports the outcome of revascularization treatment in necrotic
      immature molars. During treatment, a tri antibiotic mix was used to disinfect the
      pulp for 2 weeks. Then a blood clot was created in the canal, over which mineral
      trioxide aggregate was placed. After 24 months, the immature molars showed
      continuation of root development. The patients were asymptomatic, no sinus tracts
      were evident and apical periodontitis was resolved Results from these cases show
      that revascularization/regeneration using 3Mix-MP method could be effective for
      managing immature permanent molar teeth with pulpal necrosis.

PMID- 23855166
TI  - Relationship between severe early childhood caries and body mass index.
AB  - AIM: This study was undertaken to evaluate the relationship between Severe Early
      Childhood Caries (S-ECC) and Body Mass Index (BMI) in the absence of any
      underlying medical condition for the school going (3 to 6 years old) children of
      Mathura city, India. METHOD: One hundred caries free children (50 boys and 50
      girls) and one hundred children (50 boys and 50 girls) affected with S-ECC in the
      age range of 3-6 years without any contributing medical history were included in
      the study. Measurements of the weight (kg) and height (m) were done using a
      standard balanced beam scale and stadiometer. The BMI (kg/m2) was determined and
      the body weight status was evaluated using CDC based classification for each
      child. Independent t-test was used to evaluate whether the weight, height and BMI
      of S-ECC children is significantly different from caries free children. RESULT:
      Although the weight of the S-ECC children is more when compared to the normal
      children, the difference is not statistically significant. However, the mean BMI
      of S-ECC children is more when compared to the caries free children which was
      found to be statistically significant at p < 0.05. The body weight status of the
      Normal and S-ECC affected children based on the CDC classification revealed that
      48% have been classified in underweight category and 43% in normal weight
      category and very few children are found to be at risk of overweight and
      overweight. CONCLUSIONS: A positive correlation between the BMI and S-ECC was
      observed in this study. 51% of caries free children and 45% of S-ECC children
      were classified in underweight category based on CDC classification.

PMID- 23855167
TI  - Propolis and commonly used intracanal irrigants: comparative evaluation of
      antimicrobial potential.
AB  - The objective of endodontic therapy is not just simple cleaning and filling of
      root canals, but successful treatment requires the establishment of a sufficient
      level of disinfection. AIM: To evaluate, in vivo, the antimicrobial and
      inflammatory/irritant potential of Propolis against mixed endodontic aerobic and
      anaerobic bacteria. METHOD: An in vivo randomized controlled trial was conducted
      in a group of 60 children aged 6-12 years presenting with an acute apical abscess
      of the maxillary primary molars. Fifteen children each were divided randomly into
      four groups where irrigation during pulpectomy was performed using either 2%
      chlorhexidine, 4% calcium hydroxide or 4% Dimethyl Sulfoxide (DMSO) extract of
      propolis with normal saline as the control irrigant. Microbiological samples were
      taken from the disto-buccal root canal before initiating the pulpectomy as well
      as after 3 days later and for mixed aerobic and anaerobic bacterial cultures.
      RESULTS: In all the four groups, a significant decrease in mean aerobic colony
      forming units (cfu) count was seen. Maximum change in anaerobic cfu count was
      seen with 2% chlorhexidine. CONCLUSIONS: Chlorhexidine proved to be superior
      antimicrobial agent against both endodontic aerobes and anaerobes. Calcium
      hydroxide was found to be least effective.

PMID- 23855168
TI  - A novel music based tooth brushing system for blind children.
AB  - OBJECTIVES: To assess the Oral Health Status (OHS) of visually impaired children
      in South India, to devise and implement a specially designed Oral Health
      Education (OHE) program for them and to assess its efficacy in improving their
      OHS. STUDY DESIGN: OHS of 98 institutionalized visually impaired children aged 6
      to 14 years were evaluated at the start of the study (Pre-OHE level) using the
      Modified Gingival Index (MGI), the Turesky-Gilmore-Glickman modification of the
      Quigley Hein Plaque Index (MQHPI) and Streptococcus mutans colony count. Oral
      Health Education was imparted with the help of specially designed models and
      tooth-brushing taught with specially formulated music aided instructions in a
      song format. These parameters were re-evaluated after a period of reinforced (two
      weeks and one month) and non-reinforced (two months) tooth-brushing. RESULTS:
      Mean values of MGI and MQHPI showed a statistically very highly significant drop
      from the Pre-OHE level to the end of both the periods of reinforcement and non
      reinforcement. There was a significant decrease in the S. mutans counts from the
      Pre-OHE levels to the period of non-reinforcement (p < 0.0005). CONCLUSION: The
      OHE program specially formulated for the visually impaired children was effective
      in improving their OHS significantly

PMID- 23855169
TI  - Comparative evaluation of antimicrobial efficacy of various root canal filling
      materials along with aloevera used in primary teeth: a microbiological study.
AB  - AIM: this study was conducted to evaluate the antimicrobial effectiveness of 6
      root canal filling materials and a negative control agent against 18 strains of
      bacteria isolated from infected root canals of primary molar teeth using agar
      diffusion assay. MATERIALS: Aloevera with sterile water Zinc oxide and Eugenol,
      Zinc oxide-Eugenol with aloevera, Calcium hydroxide and sterile water, Calcium
      hydroxide with sterile water and aloevera, Calcium hydroxide and Iodoform
      (Metapex) and Vaseline (Control). MIC and MBC of aloevera was calculated.
      RESULTS: All materials except Vaseline showed varied antimicrobial activity
      against the test bacterias. The zones of inhibition were ranked into 4 inhibition
      categories based on the proportional distribution of the data. All the 18
      bacterial isolates were classified under 2 groups based on Gram positive and Gram
      negative aerobes. Statistical analysis was carried out to compare the
      antimicrobial effectiveness between materials tested with each of the bacterial
      groupings. CONCLUSION: Aloevera + Sterile Water was found to have superior
      antimicrobial activity against most of the microorganisms followed by ZOE +
      Aloevera, calcium hydroxide + Aloevera, ZOE, calcium hydroxide, Metapex in the
      descending order and Vaseline showed no inhibition.

PMID- 23855170
TI  - A two-year clinical evaluation of glass ionomer and ormocer based fissure
      sealants.
AB  - The objective of the present study provides further data comparing retention,
      marginal integrity and caries preventive effects of two fissure sealants (glass
      ionomer based; GC Fuji VII Capsule [Fuji VII] and ormocer based; Admira Seal
      [AS]) in children. This study was designed as a randomized single-blind clinical
      trial. The permanent first molars (PFMs) of 50 children, 7-13 years of age (mean
      age: 8.9 +/- 1.3 years), were sealed with a split-mouth design. Fissure sealants
      applied to the PFMs according to the manufacturer's recommendations by one
      pediatric dentist. Clinical evaluation of the sealants was carried out to record
      retention, marginal integrity and presence of caries at 6, 12, 18 and 24 months
      after placement by the other pediatric dentist. Kaplan-Meier survival analysis
      and Cox's regression models were used to estimate the probability of two sealants
      success. RESULTS: Alpha and Bravo retention rates at the end of follow-up were
      13% and 80% for Fuji VII and 3% and 83% for AS, respectively. For retention and
      marginal integrity between fissure sealants was found similar survival rates (p >
      0.05). After 24 months, presence of caries was 16% for Fuji VII and 32% for AS (p
      < 0.05). CONCLUSION: Fuji VII and AS exhibited similar retention and marginal
      integrity during 24 months. However Fuji VII was showed better results than AS
      for caries preventive effect. Consequently, Fuji VII sealants may be a better
      choice for preventing occlusal caries.

PMID- 23855171
TI  - Chemomechanical caries removal in primary molars : evaluation of marginal leakage
      and shear bond strength in bonded restorations--an in vitro study.
AB  - OBJECTIVES: To evaluate and compare the efficiency, marginal leakage and shear
      bond strength of Carisolv and Papacarie in primary molars. METHOD: Freshly
      extracted 60 human carious primary molars were randomly divided into two
      experimental groups--Group I [caries removal by Carisolv] and Group II [caries
      removal by Papacarie]. The amount of time taken for complete caries removal was
      recorded using a stopwatch. After bonded restorations, both the experimental
      groups were further randomly subdivided into four experimental groups and
      subjected to marginal leakage and shear bond strength evaluation. RESULTS:
      Papacarie [337.67 +/- 18.13] was clinically more efficient than Carisolv [461.33
      +/- 27.76] in removing caries with respect to time in seconds. 66.7% of teeth
      treated with Carisolv did not show any marginal leakage as compared to 20% with
      Papacarie. The mean [ +/- SD] shear bond strength of Carisolv [9.67 +/- 3.80]
      treated teeth was slightly more when compared to Papacarie [8.36 +/- 4.51].
      CONCLUSION: Papacarie was clinically more efficient in caries removal but showed
      significantly more marginal leakage than Carisolv.

PMID- 23855172
TI  - Deproteinization treatment on bond strengths of primary, mature and immature
      permanent tooth enamel.
AB  - OBJECTIVE: The aim of this study was to examine the effect of pre-post
      deproteinization treatment with 5% sodium hypochloride on shear bond strength
      (sbs) of adhesive resin to primary, immature and mature permanent teeth enamel.
      METHOD: 30 teeth were used for each of primary, immature and mature permanent
      teeth groups. (totally 90). In control groups, enamel was etched for 60s with 37%
      phosphoric acid (3M) and rinsed for 10s (Procedure A). In experimental groups,
      deproteinization was applied with 5% NaOCI solution for 120s before (Procedure
      D+A) and after acid-etching (Procedure A+D). Gluma Comfort Bond (Heraeus-Kulzer)
      and Charisma (Heraeus-Kulzer) composite resin were applied to etched enamel
      surfaces. Data were determined with Two-Way ANOVA and LSD Multiple Comparison
      Test (p < 0.05). RESULTS: SBS was significantly lower in primary and immature
      permanent teeth than mature permanent teeth (p < 0.05). "Procedure A+D"
      statistically increased sbs values in primary and immature permanent teeth (p <
      0.05). CONCLUSION: Deproteinization after acid etching significantly enhanced the
      shear bond strength values in primary and immature permanent teeth.

PMID- 23855173
TI  - Effect of laser and air abrasion pretreatment on the microleakage of a fissure
      sealant applied with conventional and self etch adhesives.
AB  - AIM: The purpose of this study was to investigate the effects of different
      pretreatment protocols along with different bonding agents on the microleakage of
      a fissure sealant material. METHOD: A total of 144 freshly extracted noncarious
      human third molars were used The teeth were randomly assigned into three groups
      with respect to the pretreatment protocol employed: A. Air Abrasion B. Er,Cr:YSGG
      laser C. No pretreatment (Control). In each group specimens were further
      subjected to one of the following procedures before application of the sealant:
      1. %36 Phosphoric acid-etch (AE) (DeTrey Conditioner 36/Denstply, UK)
      2.AE+Prime&Bond NT (Dentsply, UK) 3. Clearfil S3 Bond (Kuraray, Japan) 4.
      Clearfil SE Bond (Kuraray, Japan). All teeth were sealed with the same fissure
      sealant material (Conseal F/SDI, Australia). Sealed teeth were further subjected
      to thermocycling, dye penetration test, sectioning and quantitative image
      analysis. Statistical evaluation of the microleakage data was performed with two
      way independent ANOVA and multiple comparisons test at p = 0.05. For qualitative
      evaluation 2 samples from each group were examined under Scanning Electron
      Microscopy. RESULTS: Microleakage was affected by both the type of pretreatment
      and the subsequent bonding protocols employed (p < 0.05). Overall, the highest
      (Mean = 0.36 mm) and lowest (Mean = 0.06 mm) microleakage values were observed in
      samples with unpretreated enamel sealed by S3+Conseal F and samples with laser
      pretreated enamel sealed by Acid Etch+Prime&-Bond+Conseal F protocols,
      respectively (p < 0.05). In the acid-etch group samples pretreated with laser
      yielded in slightly lower microleakage scores when compared with unpretreated
      samples and samples pretreated with air abrasion but the statistical significance
      was not important (p = 0,179). Similarly, when bonding agent is applied following
      acid-etching procedure, microleakage scores were not affected from pretreatment
      protocol (p = 0,615) (intact enamel/laser or air-abrasion). For both all-in one
      and two step self etch adhesive systems, unpretreated samples demonstrated the
      highest microleakage scores. CONCLUSIONS: For the groups in which bonding agent
      was utilized, pretreatments did not effected microleakage. Both the tested
      pretreatment protocols and adhesive procedures had different effects on the
      sealing properties of Conseal F in permanent tooth enamel.

PMID- 23855174
TI  - Characterization of periodontal biofilm in Down syndrome patients: a comparative
      study.
AB  - The aim of this study was to characterize the main periodontal bacterial species
      in Down syndrome (DS) patients with and without periodontitis. METHOD: This cross
      sectional study involved 75 DS patients, 45 with and 30 without periodontitis.
      Informed consent, health and dental questionnaires and periodontitis diagnosis
      were performed PCR and LAMP assays were performed on subgingival dental plaque
      sample. RESULTS: Tannerella forsythia was the most frequent bacteria detected in
      the group with and without periodontitis (95.5 and 63.3%) followed by Treponema
      denticola (88.8 and 50%) and Porphyromonas gingivalis (53.3 and 25%
      respectively). There were statistical differences between groups (p < 0.05). Pg
      fimA type I was the most frequent Porphyromonas gingivalis genotype. Two
      different sets of primers (Aa-F/Aa-R and ltx3/ltx4) were used to detect
      Aggregatibacter actinomycetemcomitans and different frequencies were obtained,
      (68% and 14.6% respectively), they had a weak correlation (Cohen Kappa = 0.16).
      After sequencing of PCR products, ltx3/ltx4 showed more specificity. JP2 clone of
      A. actinomycetemcomitans was not detected in any sample. CONCLUSIONS: The
      composition of oral biofilm is fundamental for the development of periodontal
      disease independently of immunological alterations associated with DS. The
      frequency of detection of A. actinomycetemcomitans reported in the literature has
      a wide range, because the primers and probes applied

PMID- 23855175
TI  - Spontaneous regression of a congenital epulis in a newborn.
AB  - A 3 day old girl presented with lobulated mass protruding from her mouth. The
      mass was clinically diagnosed as a congenital epulis. The child had no airway
      obstruction and was able to feed well. A conservative treatment was proposed with
      monthly follow up appointments to monitor the lesion. After 10 months the lesion
      completely regressed and the eruption of maxillary anterior teeth remained
      unaffected

PMID- 23855176
TI  - Sedative effects of oral midazolam, intravenous midazolam and oral diazepam in
      the dental treatment of children.
AB  - OBJECTIVE: To evaluate and compare the behavioral changes and effect of sedative
      techniques in pediatric dental patients using Oral Midazolam, Intravenous
      Midazolam and Oral Diazepam as sedative agents. METHOD: Triple blind randomized
      control trial with 40 patients aged between 2-10 years, exhibiting definitely
      negative behavior was considered. Patients were randomly assigned to one of the
      four treatment groups. Group I received midazolam 0.5 mg/kg orally, Group II
      received 0.5 mg/kg diazepam orally, Group III received 0.06 mg/kg midazolam
      intravenously and Group IV received oral placebo. Behavioral changes (sleep,
      crying, movement, and overall behavior) and effect of sedative techniques on
      pediatric patients were assessed. RESULTS: All the patients in group 3 were
      significantly better in post administrative behavior viz. sleep, crying and
      movement. Over all behavior scores for group 3 patients were significantly better
      than other three groups (p < 0.001). Positive behavior of patients in group 2 and
      3 did not show significant difference but positive behavior in group 3 was
      significantly (p < 0.05) more than group 2. Placebo group showed the highest
      negative behavior CONCLUSION: Sedative effects of oral midazolam and oral
      diazepam were comparable, where as intravenous midazolam produced more sedation.
      Anxiolysis was found to be more in both the midazolam groups than the diazepam
      group. Most number of positive changes were observed in midazolam groups as
      compared to diazepam group.

PMID- 23855177
TI  - Cyclic neutropenia presenting as recurrent oral ulcers and periodontitis.
AB  - BACKGROUND: Cyclic neutropenia (CN) is a rare congenital disease that can present
      with recurrent oral ulcers and periodontitis. CN can easily be misdiagnosed as
      major recurrent aphthous stomatitis (MaRAS) or aggressive periodontitis (AP) in
      dental clinics. We describe the case of an 8-year-old boy with CN, and compare
      the oral manifestations of CN with those of MaRAS and AP. CASE REPORT: An 8-year
      old boy presented with a history of recurrent oral ulcers, periodontal
      destruction, pharyngitis and otitis media since the age of 3 months. Repeated,
      routine blood tests showed 1-week-long neutropenic periods that occurred at
      intervals of 2 weeks. A bone marrow cytology test during a neutropenic period
      demonstrated a decrease in granulocyte count. During a 2-year follow-up, his
      symptoms were well controlled by regular administration of granulocyte colony
      stimulating factor and periodontal maintenance. CONCLUSION: Several clinical
      features help to differentiate CN from MaRAS and AP Early recognition of the
      systemic cause of oral symptoms is important.

PMID- 23855178
TI  - Evaluation of salivary sialic acid levels in acute lymphoblastic leukemic
      children and its correlation with dental caries experience.
AB  - AIM: The aim of present study was to evaluate the salivary sialic acid levels in
      Acute Lymphoblastic Leukemic (ALL) children and to correlate it with dental
      caries experience. METHOD: A total of 120 children aged 4-10 yrs were divided
      into 4 groups of 30 each. Dental caries experience was recorded followed by un
      stimulated saliva collection. RESULTS: The mean salivary sialic acid levels of
      the study group were much higher when compared with the control group, which was
      statistically significant. A linear relationship between salivary sialic acid
      levels and dental caries in leukemic children was observed. CONCLUSION: The
      findings of our study conclude that salivary sialic acid levels may have a potent
      activity in dental caries process and can be used as a useful marker in cancer

PMID- 23855179
TI  - Maternal education, dental visits and age of pacifier withdrawal: pediatric
      dentist role in malocclusion prevention.
AB  - OBJECTIVE: Although discouraged, pacifier usage is widespread and often practiced
      beyond two years of age. The current study explored the effects of maternal
      education and dental visits on the age of pacifier withdrawal. STUDY DESIGN: The
      dental histories of 213 children (53.1% male) attending a primary school in
      Madrid were obtained along with maternal education level and age at pacifier
      withdrawal. Data were analyzed by using independent samples t-test, one-way ANOVA
      two-way ANOVA and a complementary non-parametric approach was also used. RESULTS:
      There was a significant effect of maternal education on the age of pacifier
      withdrawal; the higher the maternal education, the younger the age of withdrawal.
      The frequency of dental visits influenced the relationship between maternal
      education and the age of pacifier withdrawal. Dental visits considerably
      shortened pacifier use among children with low- and medium-educated mothers.
      CONCLUSIONS: Pediatric dentists play a critical role in the correction of
      unhealthy oral habits such as prolonged pacifier use. The educational component
      of pediatric dentistry could reverse the lack of knowledge or misinformation
      among high-risk groups (e.g. low maternal education). As a consequence, we
      recommend that children start dental visits at an early age and maintain visits
      with a high frequency.

PMID- 23855180
TI  - Differences in pain perception in children reporting joint and orofacial muscle
      pain.
AB  - PURPOSE: To determine changes in orofacial pain perception in community-based
      children by assessing the pressure pain threshold (PPT) with an algometer and
      pain intensity by manual palpation (MP). METHODS: A total of 100 children from
      the community aged 7 to 12 years were assessed. Thirty-eight children reported
      pain in the orofacial region. Of these children,10 reported joint pain (GJ), 12
      reported joint and muscle pain (GJMM), 5 reported muscle pain (GMM), 11 reported
      pain during mastication (GMAST), and 62 reported no pain. An ANOVA (p < 0.05) was
      used to determine the differences in pain intensity and PPT among groups.
      RESULTS: Significantly higher pain intensity upon MP was observed for the
      temporalis muscle in the GJMM, GMAST and GJ groups compared to the remaining
      groups. The PPT values were significantly lower in the masseter temporalis
      muscles, TMJ and thenar region in the GJMM group compared to the other groups.
      CONCLUSION: MP more accurately differentiated symptomatic subjects from symptom
      free TMD subjects, and PPT values were more sensitive to the discrimination of
      pain in the orofacial sites assessed. In addition, the changes in perception at a
      larger number of sites among children reporting mixed pain may suggest the
      presence of a possible mechanism of central sensitization.

PMID- 23855181
TI  - Regaining leeway space and anterior crossbite correction with a modified
      maxillary molar distalizing appliance.
AB  - During the mixed dentition stage, adolescents experience rapid dental and
      skeletal development. Unfortunately, many of them do not visit the orthodontist
      early enough and miss out on the opportunity to take advantage of preventive and
      interceptive orthodontic treatment. This article describes the management of
      regaining leeway space and correcting anterior crossbite using a modified
      maxillary molar distalizing appliance.

PMID- 23855182
TI  - Biofilm associated microorganisms on removable oral orthodontic appliances in
      children in the mixed dentition.
AB  - OBJECTIVE: Biofilms on removable orthodontic appliances act as reservoir of
      microorganisms, capable of modifying the environmental condition of oral cavity
      and are difficult to be removed with routine hygiene measures. The present
      investigation includes enumeration, identification and numerical analysis of
      different types of cultivable bacteria associated with the biofilms on removable
      orthodontic appliances. STUDY DESIGN: Removable appliances of 25 healthy children
      among the ages of 10 to 14 years were taken to measure the prevalence of biofilms
      and type of microorganisms. For isolation of microorganism from biofilms
      different types of selective and non-selective medium based on standard methods
      were used. The data were further analysed by using Kolmogorov-Smirnov test, one
      sample t-test and Spearman rank correlation coefficient. The percentage
      frequencies of isolates were also calculated RESULTS: The survey revealed the
      presence of both multi-species and mono species biofilms on appliances, with Non
      Streptococci, anaerobic bacteria, Streptococcus spp., members of the family
      Enterobacteriaceae and Lactobacillus spp. as a dominant microbial flora of
      biofilms. Bacillus sp. and Candida sp. were isolated from one sample each.
      Significant positive and negative correlations were established among the species
      isolated from biofilms. CONCLUSION: Higher prevalence of the members of the
      family Enterobacteriaceae were reported during this study, advocating an extra
      hygienic measure is essential for this age group while wearing acrylic
      orthodontic appliances in oral cavity.

PMID- 23855183
TI  - Job characteristics, core self-evaluations, and job satisfaction: what's age got
      to do with it?
AB  - There is a well-established relationship between age and job satisfaction. To
      date, there is little research about how many well-known predictors of job
      satisfaction, specifically job characteristics and core self-evaluations, may
      vary with age. Using a multi-worksite sample of 1,873 employed adults aged 17 to
      81, this study evaluated the extent to which several job characteristics and core
      self-evaluations varied in their relationships with job satisfaction for workers
      of different ages. Findings suggest that the positive relationships between job
      satisfaction and skill variety, autonomy, and friendship weaken as employee age
      increases, while the positive relationships between job satisfaction and dealing
      with others, task identity, task significance, feedback, and core self
      evaluations did not vary with age. The findings extend previous research by
      examining how the factors important for job satisfaction vary for employees of
      different ages.

PMID- 23855184
TI  - Older men's lay definitions of successful aging over time: the Manitoba follow-up
      study.
AB  - The concept of "successful aging" has become widely accepted in gerontology, yet
      continues to have no common underlying definition. Researchers have increasingly
      looked to older individuals for their lay definitions of successful aging. The
      present analysis is based on responses to five questionnaires administered to
      surviving participants of the male Manitoba Follow-up Study cohort (www.mfus.ca)
      in 1996, 2000, 2002, 2004, and 2006 (n = 2,043 men were alive at a mean age of 78
      years in 1996). One question on each survey asked: "What is YOUR definition of
      successful aging?" Applying content analysis to the 5,898 narratives received
      over the 11 years, we developed a coding system encompassing 21 main themes and
      86 sub-themes defining successful aging. We quantitatively analyzed trends in
      prevalence of themes of successful aging prospectively over time. Our findings
      empirically support colleagues' past suggestions to shift from defining
      successful aging in primarily biomedical terms, by taking lay views into account.

PMID- 23855185
TI  - Predictors and characteristics of successful aging among men: a 48-year
      longitudinal study.
AB  - To explore dimensions of successful aging, 71 men were selected for healthy
      adjustment and were prospectively studied in young adulthood (average age 20) and
      reassessed in 32-year and 48-year follow-ups. Despite an increase of medical
      problems, most men maintained healthy adjustment in early old age. At both follow
      ups, successful young adult predictors of favorable overall outcome included good
      peer social adjustment, an absence of troubled parental discipline, and an
      absence of immature defensive behaviors when angry. However, young adult factors
      were more predictive of outcomes in middle age than in early old age, as
      predictor effect sizes decreased between the first follow-up and the second
      follow-up 16 years later. Findings support the possibility of both favorable and
      unfavorable changes in the second half of life that may diminish the impact of
      some young adult characteristics and family environments on adjustment in early
      old age.

PMID- 23855186
TI  - [Alkaline phosphatase activity in blood group B or O secretors is fluctuated by
      the dinner intake of previous night].
AB  - We previously reported that two intestinal alkaline phosphatase (IAP) isoforms,
      high molecular mass IAP (HIAP) and normal molecular mass IAP (NIAP), appear in
      healthy serum with our Triton-PAGE method for determination of ALP isozymes. In
      addition, HIAP is chiefly present in blood group B or O secretors, and a large
      amount of NIAP is secreted into the circulation after high-fat meal in blood
      group B or O secretors. In the present paper, we investigated the relationship
      between alkaline phosphatase (ALP) activity in early morning with the patient in
      a fasted state and the dinner intake of previous night. Two types of dinner were
      prepared; a low-fat meal (520 kcal), and a high-fat meal (1,040 kcal). Subjects
      ate the 2 types of dinner on different days. The mean ALP activities at 14 h
      after high-fat meal ingestion in blood group B or O secretors (n=14) from JSCC
      and IFCC methods were 8.8% and 5.2% higher than those at 14 h after low-fat meal
      ingestion in blood group B or O secretors, respectively. The increases in ALP
      activity between after high-fat meal and low-fat meal were nearly identical to
      the increases in NIAP activity. These results suggest that a high-fat meal is
      more likely to affect ALP activity at the early morning with the patient in a
      fasted state in blood group B or O secretors.

PMID- 23855187
TI  - [Histochemical stains for minerals by hematoxylin-lake method].
AB  - The present study was undertaken to establish the experimental animal model by
      histological staining methods for minerals. After intraperitoneal injections of
      minerals, precipitates deposited on the surface of the liver. Liver tissues were
      fixed in paraformaldehyde, embedded in paraffin and cut into thin sections which
      were used as minerals containing standard section. Several reagents for
      histological stains and spectrophotometry for minerals were applied in both test
      tube experiments and stainings of tissue sections to test for minerals.
      Hematoxylin-lake was found of capable of staining minerals in tissue. A simple
      technique used was described for light microscopic detection of minerals.

PMID- 23855188
TI  - [A role of the platelet receptor CLEC-2 in lymphangiogenesis and its clinical
      application].
AB  - Platelets play a pivotal role in thrombosis and hemostasis; however, a series of
      recent research has demonstrated that platelets also play roles other than in
      clotting. We discovered that a platelet receptor, C-type lectin-like receptor 2
      (CLEC-2), facilitates lymph/blood vessel separation in the developmental stage by
      binding to its ligand, podoplanin, on lymphatic endothelial cells. We have
      previously reported that CLEC-2-deficient mice showed blood-filled lymphatic
      vessels and severe edema, suggesting that CLEC-2 is essential for lymph/blood
      vessel separation; however, its mechanism has not been elucidated to date.
      Although CLEC-2 is mainly expressed in platelets and megakaryocytes, marginal
      expression is observed in other blood cells in mice. We found that specific
      deletion of CLEC-2 from platelets/megakaryocytes also impaired blood/lymphatic
      vessel separation, suggesting that CLEC-2 in platelets is required for
      separation. Based on several in vitro experiments, we proposed the mechanism of
      blood/lymphatic vessel separation as follows: In the developmental stage, when
      lymphatic vessels separate from cardinal veins, CLEC-2 in platelets binds to
      podoplanin in lymphatic endothelial cells. Subsequent platelet activation results
      in the release of platelet granule contents, including the transforming growth
      factor 8 family. These platelet contents inhibit migration, proliferation, and
      tube formation of lymphatic endothelial cells, which facilitates blood/lymphatic
      vessel separation. We also found that soluble CLEC-2 is released upon platelet
      activation. We hypothesized that plasma soluble CLEC-2 could be a marker of
      thrombosis and established an ELISA system to measure soluble CLEC-2. Although
      current tests for in vivo platelet activation require special methods for blood
      sampling, soluble CLEC-2 can be measured with ordinary blood sampling. We are now
      investigating the potential of soluble CLEC-2 as a useful marker for in vivo
      platelet activation.

PMID- 23855189
TI  - [Recent changes in the therapeutic strategy for NSCLC in association with new
      anti-cancer agents].
AB  - Patients with SCLC (Small cell lung cancer) have been treated differently from
      those with NSCLC (New-small cell lung cancer) as a different disease. Recently,
      even patients with NSCLC are treated differently according to histological
      subtypes. This change is associated with the development of new drugs,
      particularly molecular-targeted drugs. Because Bevacizumab can cause serious
      adverse effects, patients with squamous cell carcinoma histology and a history of
      hemoptysis are contraindicated for this drug. Pemetrexed has been approved with
      an anti-mesothelioma drug and was confirmed to be effective for NSCLC. However,
      its efficacy was not equally proved among the histological subtypes; only
      adenocarcinoma patients showed shorter progression-free and prolonged survival
      periods. Regarding tyrosine kinase inhibitors, the targeted gene alterations
      occur specifically in adenocarcinoma. Based on these findings, the current
      therapeutic strategy for NSCLC is based on the histological subtype and
      mutational status of EGFR and ALK. In this article, transition of the therapeutic
      strategy for NSCLC, characteristics of targeted gene alterations and efficacies
      of the targeted therapy are reviewed.

PMID- 23855190
TI  - [Treatment for dyslipidemia--a strategy for the prevention of atherosclerosis].
AB  - Plasma cholesterol levels in the Japanese people gradually increased until 1990,
      possibly due to the increase in dietary cholesterol. Japan Atherosclerosis
      Society Guidelines for the prevention of atherosclerotic cardiovascular diseases
      were released in 2012. The diagnostic values of LDL-C, TG and HDL-C for
      dyslipidemia are >or= 140 mg/dL, >or=150 mg/dL and <40 mg/dL, respectively. The
      guidelines emphasize that these figures do not indicate a need to start drug
      therapy, but are only for dyslipidemia screening. The set point of LDL-C for the
      prevention of atherosclerosis falls with the number of risk factors. The
      guidelines recommend LDL-C calculated from the Friedewald formula, because
      homogenous assay kits for LDL-C still have problems in terms of accuracy. It is
      obvious that long-term excessive cholesterol consumption affects the plasma
      cholesterol level. It is thus necessary to restrict dietary cholesterol intake,
      at least for hypercholesterolemic patients. If the effect of dietary therapy is
      insufficient, drug therapy should be taken into consideration. Statins, HMG-CoA
      reductase inhibitors, are most commonly used worldwide for hypercholesterolemic
      patients and fibrates are effective for hypertriglyceridemia. When we use these
      two drugs in patients with type IIb dyslipidemia, we should pay attention to side
      effects, including rhabdomyolysis. On the other hand, ezetimib is a new type of
      cholesterol-lowering drug and is an inhibitor of cholesterol transport in the
      small intestine. Thus, the combination of ezetimib and statins can reduce LDL-C
      more than therapy with each drug alone.

PMID- 23855191
TI  - [Case conference of hematological diseases based on the morphology of blood
      cells: Chairman's introductory remarks].
AB  - A case conference of hematological diseases based on the morphology of blood
      cells was held as a Joint Symposium of JSLM and JSLH. Four cases were presented
      and discussed mainly from the viewpoint of morphology: a case of acute leukemia
      with basophilia, two cases of acute leukemia and another malignancy, and a case
      of bone marrow invasion of malignant melanoma. Each case included pathological
      and curious morphological findings to be carefully examined and intensively
      discussed by the commentators and participants. Differential diagnosis of
      immature or abnormal blastic cells was found to be particularly important.
      Finally, each presenter elucidated the final diagnosis of their own case and
      added an explanation. The importance of morphological evaluation was reconfirmed
      at this conference.

PMID- 23855192
TI  - [Practical approach to infection control and antimicrobial stewardship by medical
      technologists].
AB  - Since establishing an antimicrobial management team (AMT) in 2003, we have been
      promoting both appropriate diagnosis and treatment and improving the prognosis of
      hospitalized patients with infections. AMT is composed of 4 doctors, 2 nurses, 2
      pharmacists and one medical technologist. AMT members meet twice a week and
      discuss patients with positive blood cultures, with prescribed anti-MRSA drugs
      and suspected infections. Antimicrobial prescription and clinical laboratory data
      are obtained from the database of electric medical records and microbiological
      data from the laboratory database system. The initial step in infection control
      and antimicrobial stewardship is an accurate diagnosis of infection. Clinical
      microbiology laboratories play a critical role in infection control and
      antimicrobial stewardship by reporting accurate and timely results of both
      bacterial identification and antimicrobial susceptibility tests. Medical
      technologists are required to develop better competency and proficiency about
      clinical microbiology in both infection control and antimicrobial stewardship.

PMID- 23855193
TI  - [Career planning for explanation of clinical test results and program of
      inspections: developing medical technologists for team medical care].
AB  - Current medical care is subdivided according to medical advances, and
      sophistication and new techniques are necessary. In this setting, doctors and
      nurses have been explaining to and consulting patients about their medical
      examinations; however, in recent years, medical technologists have performed
      these duties at the start of the team's medical care. Therefore, we think it is
      possible for patients to receive clear and convincing explanations. Most patients
      cannot understand their examination data, which are written using numbers and
      charts, etc. Recently, the Nagano Medical Technologist Society has been
      developing technologists who could explain examination results to patients. This
      development training included hospitality and communication. The certificate of
      completion will be issued in March when the program starts.

PMID- 23855194
TI  - [Emergency medical service system for elderly patients].

PMID- 23855195
TI  - [Emergency medical services in a hyper-aged society].
AB  - The number of people aged 65 and older in Japan has reached 23.3%. The annual
      rate of presentations to hospital emergency departments(ED) has increased
      substantially and older patients are represented in this increase. By 2060 the
      number of people aged 65 and over is expected to double to 40%, and ED transfers
      and hospital admissions will increase significantly. Facilities will need to plan
      to accommodate increasingly greater demands for ED and hospital services.

PMID- 23855196
TI  - [Emergency medical services for the elderly: present fact and future challenge].
AB  - The Tokyo Fire Department (TFD) ambulance units are transporting more people than
      ever before with elderly patients on the increase. The TFD then set up the
      Emergency Telephone Consultation Center in 2007 to help citizens properly use EMS
      services, asking non-emergency cases to go to the hospital by themselves or
      sending the ambulance to serious cases. Transportation of all "home patients"
      (receiving medical services at home, not in the hospital) by fire department
      ambulances would leave really serious patients behind. Consequently, it is
      important to make the most of private sector ambulances and hospital ones. For
      community life safety, making the most of local resources, as well as the fire
      department-hospital cooperation, is much more needed now.

PMID- 23855197
TI  - [Preventive medicine and care for the elderly population in the super-aged
      society].
AB  - Prevention, particularly with regard to older people, has assumed increasing
      importance in policy in recent years. Prevention not only focuses on diseases but
      also on the geriatric syndrome and frailty must be crucial for the well-being of
      older people in the super-aged society. The preventive services aim to sustain
      independent living among those who are vulnerable and the preventive strategies
      should be supported by an evidence base that links risk factors with particular
      conditions and interventions to reduce risk and ameliorate the impact of illness
      and impairments. However, due to the heterogeneity of this population and a
      paucity of research on this field, it is difficult to make universal
      recommendations for the preventive services for the older people.

PMID- 23855198
TI  - [Frailty and geriatric syndrome].
AB  - Frailty comes from decline of functions in multi-organs, not a single organ
      dysfunction (disease). This accounts for comorbidity in the elderly, both in the
      acute and chronic ill conditions. In the Kyorin University Hospital, which have a
      role of emergency hospitals in the western area of Tokyo, more than seventy
      percent of the patients admitted to the geriatric ward are emergent cases. They
      have multi-diseases; the most frequent one is pneumonia(from aspiration). Often,
      their ADL is poor and have cognitive disorders, which is why they stay in the
      ward long. Geriatric syndrome indicates signs and symptoms frequently observed in
      the elderly. Because geriatric syndromes stem from multi-system dysfunction, they
      cannot be treated well enough. However, if geriatric syndromes are left
      untreated, the ADL declines in a steady state. Usually, geriatric syndromes
      cannot be treated by medication, but well-planned care can prevent progression.
      From this sense, not a medicine but multidisciplinary approach, such as
      cooperation with nurse, dietitian, PT, OT, pharmacist, social worker, care
      programmer and others, is the key to preventing elderly people from failing to
      the disabled state.

PMID- 23855199
TI  - [Behavioral and psychological symptoms of dementia--diagnosis and treatment].
AB  - Behavioral and psychological signs and symptoms of dementia (BPSD) can be
      interpreted as cognitively impaired patients' responses to external stimuli. The
      causes of BPSD include physical, psychological, and environmental factors,
      although combinations of these factors usually contribute to the development of
      BPSD. Representative conditions that should be distinguished from dementia
      include delirium, aphasia, and depression. It is important to differentiate
      depression from apathy associated with dementia. A well-balanced combination of
      drug therapy and non-pharmacological methods is required for the treatment of
      BPSD. Non-pharmacological methods should be considered first to address moderate
      BPSD in particular. It is advisable to carefully provide drug treatment following
      environmental control and non-drug treatment, and minimize adverse effects taking
      into consideration the physical characteristics of the elderly. Regarding methods
      for formulation according to the symptom, hyper- and hypoactivity symptoms should
      be addressed separately.

PMID- 23855200
TI  - [The decreases in motor function in the elderly].
AB  - Decreases in motor function in the elderly differ from one individual to another.
      These decreases may disturb their ability to perform activities of daily living
      and locomotion. Because of the decrease in reserve capacity that comes with age,
      disuse syndrome may develop, in which the individual becomes bedridden and more
      susceptible to another diseases and injuries. Emergency medical care workers must
      have adequate understanding of the motor function of the elderly. Prevention of
      disuse syndrome with early rehabilitation must be a top priority.

PMID- 23855201
TI  - [Age-associated decline in the immune system].
AB  - Most countries in the world, led by Japan are recently burdened with a tremendous
      growth of elderly population. Unfortunately, to continue this trend is to
      guarantee the increase the number of age-related diseases such as infection or
      cancer in the very elderly, since our various biological functions are getting
      fragile and dysfunction with advancing age. Especially, immunological responses,
      such as susceptibility to infection or reduced response to vaccination linked to
      immunological memory, are also gradually impaired and reached in
      'immunosenescence', although its defined molecular mechanism remains veiled. This
      article first summarizes the alterations in the quantity and quality such as
      numbers and functions as well as lymphocyte development and homeostasis in
      adaptive immunity, known to be primarily affected by immunosenescence.
      Continuously, another age-related alterations of innate immunity recognized as
      the first defense barrier with some inflammatory mediators and phagocytosis are
      also introduced.

PMID- 23855202
TI  - [Changes in pharmacokinetics in elderly patients].
AB  - Age-related physiological and morphological changes may influence drug
      disposition. Age-related decreases in gastric acid secretion, gastrointestinal
      motility and blood flow may alter drug absorption, but no significant age-related
      change in drug absorption is observed. With aging, body fat increases and total
      body water decreases. Therefore, water-soluble(hydrophilic) drugs have a higher
      peak plasma levels in the elderly. Inversely, lipid-soluble (lipophilic) drugs
      have an increased volume of distribution in the elderly. Age-dependent decrease
      in the serum albumin concentration influences drug protein binding potency. Age
      related reduction in liver size, hepatic blood flow and hepatic drug-metabolizing
      enzyme activity decreases the hepatic drug clearance. The decreases in renal
      blood flow, glomerular filtration rate (GFR) and tubular secretion have a
      considerable impact on the renal clearance of drugs.

PMID- 23855203
TI  - [Impaired consciousness].
AB  - Consciousness disorder is one of the common signs that clinicians treat every
      day. It is further more frequently found in elderly patients, but it is often
      difficult to make an exact diagnosis and to give a suitable treatment for each
      case. There are many kinds of diseases or systemic disorders which impair
      consciousness, and moreover, various backgrounds (e.g. their lifestyle, mental
      problems, etc.) characteristic for aged people often make the diagnosis unclear.
      Therefore, it is very important for every physician assigned to emergency room to
      have broad viewpoint and to make careful examinations approaching such patients.
      Needless to say, if the patient is facing crisis, more priority should be given
      to emergency treatment than to precise diagnosis.

PMID- 23855204
TI  - [Seizure].
AB  - Seizure is defined as "a strong shrinkage state of the skeletal muscle which is
      involuntary, and occurs spasmodically" and it is often accompanied by disturbance
      of consciousness. The typical disease which causes seizure is epilepsy. But there
      is many conditions causing seizure. Therefore, diagnosis of epilepsy should be
      careful. Seizure among eldery increases in an era of an aging population in
      Japan. The risk of recurrence of seizure or epilepsy in elderly is higher than
      that in youth. In considering of the treatment of seizure among elderly,
      differential diagnosis from various condition must be done.

PMID- 23855205
TI  - [Behavior abnormality].
AB  - The aging rate of Japan is higher than 20% in 2005 and it is predominantly early
      and invites aged society in the developed countries. With increase in elderly
      person population, the emergency consultation of the elderly person increases,
      and the emergency medical treatment of the elderly person that complaining of a
      condition is vague must be careful to have possibilities to miss the severe
      condition of a patient. When an elderly person presents with sudden behavior
      abnormality and consults an emergency room, we must check presence of disturbance
      of consciousness. When there is disturbance of consciousness, we provide
      treatment for it. In this report, we describe an emergency disease with the
      behavior abnormality of the elderly person.

PMID- 23855206
TI  - [Dysphagia].
AB  - Swallowing function is deteriorated with age, and swallowing disorders can cause
      aspiration pneumonia that is the one of main causes of death for elderly.
      Accordingly, evaluation technique for swallowing function is important. Roughly,
      these are screening test and instrumental examination. Modified water swallowing
      test and cough test are valuable screening test for detecting dysphagia.
      Videofluorography and videoendoscopy as instrumental examination are definitive
      evaluation for swallowing function. These tests or examinations are useful to
      evaluate swallowing, but in other words, these evaluations are evaluative method
      only for swallowing. Therefore, other informations, such as age, phase of
      disease, nutrition status, dementia, teeth problem, or meal environment, should
      be taken into consideration when we decide feeding method of patients.

PMID- 23855207
TI  - [Urinary retention].
AB  - Urinary retention is a lack of ability to urinate. In acute case of urinary
      retention, some associated symptoms are present such as lower abdominal
      distention and pain. It is usually a common complication of benign prostatic
      hyperplasia, prostatic cancer, urethral stricture, neurogenic bladder or
      medications (including anticholinergics and antidepressants). The ultrasound
      examination is useful for the diagnosis and shows massive increase in bladder
      capacity. The treatment requires urgent placement of a urinary catheter into the
      bladder. However, in case of difficulty for indwelling a catheter, the patient
      should be sent to the urologist.

PMID- 23855208
TI  - [Ileus and intestinal obstruction].
AB  - Ileus and intestinal obstruction are common diseases for the elderly. Ileus is
      caused as the results of severe pain, infections and medications. Intestinal
      obstruction is one of the first etiologies of surgical emergency procedures.
      Intestinal obstruction is mainly due to the abdominal wall hernias and oncologic
      problems in the elderly. The fatal intestinal obstruction is not negligible in
      the elderly. Intestinal obstruction, especially in the demented elderly, can
      present late and with deceptively minimal signs and symptoms. We described the
      features and notes of ileus and intestinal obstruction in the elderly emergency
      patients.

PMID- 23855209
TI  - [Respiratory failure].
AB  - The aged patients are susceptible to respiratory failure, especially acute lung
      injury (ALI) or acute respiratory distress syndrome (ARDS). The mortality rate
      for ARDS ranges from 40-70% despite of intensive care using currently available
      drugs. However, its mechanism still remains to be elucidated. Platelet-activating
      factor (PAF) and metabolites of arachidonic acid, i.e., eicosanoids, are lipid
      mediators that have various biological effects including cell adhesion,
      endothelial cell activation and the production of cytokines. Recent studies using
      genetically-engineered mice have shown that PAF and cytosolic PLA2 (cPLA2) play
      an important role in the pathogenesis of ALI. The inhibition of these pathways,
      PAF and cPLA2, might provide a novel therapeutic approach to ALI.

PMID- 23855210
TI  - [Acute decompensated heart failure].
AB  - Acute decompensated heart failure (ADHF) is common in the elderly, who often have
      various heart diseases and co-morbidities. Another term, acute heart failure
      syndrome (AHFS) means that it is an association of heart conditions and that it
      must be treated immediately. An overview of ADHF treatment begins with common
      hyperacute-phase treatments including advanced cardiac life support, alleviation
      of dyspnea, and alleviation of congestion and/or hypo-perfusion. Non-invasive
      positive-pressure ventilation (NPPV) is often effective for dyspnea. Congestion
      and hypo-perfusion are assessed with Nohria-Stevenson classification, and should
      be properly adjusted. Then, the patients are treated differently, dependent on
      the clinical scenario, which helps to discriminate cardiac failure and vascular
      failure. After echocardiography, specific treatment for specific heart disease is
      performed.

PMID- 23855211
TI  - [Accidental falls].
AB  - Falls are common cause of injuries among elderly people, and fractures are the
      most serious consequence of falls. For seniors, hip fractures are the second
      major cause of bedridden. The feature and acute care of head injury, spinal cord
      injury, vertebrae fracture, and hip fracture are described. Just had fracture
      fixation, the patient can not go back to the original ADL. In order not to become
      bedridden, both medication and physical examination are important based on the
      new disease concept of locomotive syndrome. To do so, requires hospital and
      clinic cooperation. Sufficient cooperation is not currently possible, and spread
      of liaison service is essential.

PMID- 23855212
TI  - [Accidents during bathing].
AB  - Sudden death during bathing accounts for 10 to 15% of all out-of hospital cardiac
      arrests in Japan. Surveys in Tokyo revealed 1,085 victims of accidents during
      bathing transported by ambulance from October 1999 to March 2000. 53% of them
      were cardiac arrest and 25% were those who needed rescue from bath tub because of
      consciousness disturbance (rescued group). Clinical observation of the rescued
      group patients indicated they suffered from transient loss of consciousness
      probably because of elevated body temperature. The current hypothesis of the
      accidents during bathing is a unique type of heat illness exposed by high water
      temperature(41-43 degrees C). Geriatric population is vulnerable to the bathing
      induced heat illness.

PMID- 23855213
TI  - [Elder abuse].
AB  - The Prevention Law of Elder Abuse was enacted from April 1, 2006. There are two
      kinds of abuse by nursing family and by staff of nursing care home. In the case
      of abuse by family, 80s women were most victims and they were abused by their
      sons or husbands. While abused by staff of nursing care home, the number was
      small but increased rapidly. In the background of victims, they need high degree
      of care, and their dementia is severe. Those may affect the incident of abuse.
      Health Care workers have to examine the elders with thinking of their
      backgrounds, and it is important that we always suspect of the existence of
      abuse.

PMID- 23855214
TI  - [Postoperative care of the elderly].
AB  - Number of elderly patients undergoing surgery is increasing in Japan owing to the
      increasing population over 65. Developments of less invasive surgical techniques
      and advances in perioperative care may also contribute. Postoperative mortality
      among elderly patients are higher than that in younger patients due to decreased
      functional reserves of nervous, cardiovascular, pulmonary, hepatic and renal
      systems. Physiological changes in vital organs of the elderly and their
      influences in clinical settings are depicted. Postoperative complications in the
      elderly, including pneumonia, aspiration, myocardial infarction, delirium,
      cognitive dysfunction and cerebral infarction are described. Management and
      preventive strategies of postoperative complications are also discussed.

PMID- 23855215
TI  - [Characteristics of elderly heat illness patients in Japan--analysis from
      Heatstroke STUDY 2010].
AB  - Heatstroke Surveillance Committee of the Japanese Association for Acute Medicine
      (JAAM) collected the clinical data of 1,775 heat illness patients transported
      into 94 Emergency Medical Centers or Emergency Departments throughout Japan from
      1 July to 31 August 2010 (Heatstroke STUDY 2010). Seven hundreds and four elderly
      patients' data revealed that 541 cases (80%) suffered from classical heatstroke
      in the ordinary life and the morbidity and mortality were much higher than those
      of exertional heatstroke patients. Hypertension, diabetes, heart disease and
      dementia were the risk factors of this disease. Forty nine patients (6.9%) were
      the victims of classical heatstroke and multiple organ failure include heart
      failure was the major cause of heat related death in acute phase after admission.
      No one died in exertional heatstroke group.

PMID- 23855216
TI  - [Hypothermia, chilblain and frostbite].
AB  - Many factors such as the environmental conditions (temperature and humidity
      etc.), a nutritional status, the degree of fatigue, a moisturizing state of the
      body, clothes, the sensitivity to coldness are involved in an outbreak of
      hypothermia. Children, aged persons and the presence of an underlying disease are
      also risk factors related to the occurrence of hypothermia. The dysfunction of
      the respiratory system, the circulatory system and the central nervous system is
      caused by a decrease in body temperature. Finally, death is brought about at 25
      degrees C of body temperature or lower. Frostbite develops when tissue is exposed
      to -4 degrees C of coldness or lower. The extent of injury is determined by the
      magnitude of coldness.

PMID- 23855217
TI  - [Aged burn victims: its special features and treatment].
AB  - The percentage of aged patients in burns are enlarged today. Usually they have
      some physiological disorders and less reserve organic functions. In treatment for
      aged burn victims, special care should be taken to keep their general conditions.
      And to keep their original ADLs, super early surgical treatment is very
      effective. In post surgical period, patients need to manage both different
      conditions one is to keep rest at the operated area and the other to exercise
      active general rehabilitation. In these purpose, we use negative pressure
      dressings for skin graft instead of tie-over dressings.

PMID- 23855218
TI  - [Limits and challenges of resuscitation for the elderly in emergency and critical
      care center].
AB  - In recent years, there has been an increase in the elderly ambulance. An
      increasing number of elderly patients require hospitalization. Old age brings
      with it an increased susceptibility to respiratory diseases. Bad prehospital ADL
      (activities of daily living) results in poor, survival rate and final ADL. At
      present, the elderly are facing physical, mental and social problems, and are
      having difficulty in receiving proper emergency and critical care treatment.
      There needs to be change in the quality of emergency and critical care, one that
      focuses on life-saving while maintaining ADL. There is an urgent need for
      restructuring of the regional emergency medical system and implementing measures
      for terminal care in emergency medical care for the elderly.

PMID- 23855219
TI  - [End-of-life care in emergency settings in the super-aged society: withholding
      CPR from frail elderly with severe ADL impairment].
AB  - Emergency and intensive care unit demographics have changed with the advent of
      the super-aged society in Japan. Japan has the highest population aging rate in
      the world. It is now predicted that an increasing number of people will die at
      higher age. The oldest old individuals show increasing frailty, with an excess
      vulnerability to stressors. It is believed that frail elderly would receive
      limited benefit from highly invasive emergency treatment and advanced intensive
      care which, on the contrary, could bring about harmful effects on frail elderly.
      So far a number of frail oldest-old nursing home residents with cardiopulmonary
      arrest have been taken by ambulance to emergency medical centers to receive
      cardio-pulmonary resuscitation in vain in Japan. Now is the time to stop the
      harmful ritual. Withholding CPR from frail elderly with severe ADL impairment
      would not constitute an act of ageism but the act of humanity based on medical
      evidence.

PMID- 23855220
TI  - [Emergency medicine after a catastrophic disaster: from a view of geriatrics and
      gerontology].
AB  - The megathrust earthquake and the towering tsunami hit the east coast of Japan on
      March 11th of 2011 after intervals of 1,142 years. About 90 % of nearly 20,000
      victims were drowned in devastating waves, while every town and city along the
      coast turned out to be a ruin. Over 400,000 people were forced to move to the
      evacuation centers where the evacuees slept on the floor without electricity,
      running water or heating systems at freezing nights. Emergency medicine,
      therefore, was more required during the evacuation phase than during the acute
      phase of the tsunami disaster. Here discussed is the phenomenon that the events
      happened mostly to the elderly evacuees especially in the swept area by silty
      polluted seawater.

PMID- 23855221
TI  - [Current understanding and perspectives of lymphangioleiomyomatosis].
AB  - Lymphangioleiomyomatosis (LAM) is a slowly progressive neoplastic disease
      characterized with proliferation of abnormal smooth muscle-like cells (LAM cells)
      in the lungs and along axial lymphatics. Proliferation of LAM cells are
      considered to be driven by dysregulated mTORC1 signaling, that is caused by
      mutations in either the TSC1 or TSC2 gene in LAM cells. The MILES trial has
      successfully demonstrated that sirolimus, a mTORC1 inhibitor, can stabilize
      pulmonary function in LAM, but its effect disappears once sirolimus is
      discontinued. Limited ability of sirolimus may be due to concomitant activation
      of autophagy in LAM cells when mTORC1 activity is suppressed by sirolimus.
      Recently animal models for LAM have been independently established by several
      groups, which may provide a platform for developing drugs interfering various
      steps in disease progression.

PMID- 23855222
TI  - [Present status of gastrointestinal damage due to non-steroidal anti-inflammatory
      drugs (NSAIDs)].
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are roughly divided into a low
      dose aspirin group used for primary and secondary prevention of cardiovascular
      events and non-aspirin NSAIDs used for treatment of bone and joint diseases. Both
      cause gastrointestinal damage directly or indirectly. In the present study, we
      reviewed gastrointestinal damage due to non-aspirin NSAIDs with respect to the
      esophagus, stomach/duodenum, small intestine and colon. Damage due to NSAIDs
      occurs in all digestive tracts and since the analgesic effect of NSIADs hides
      subjective symptoms, the symptoms are often not treated until they are advanced
      to a serious state. Further, patients receiving NSAIDs are mostly elderly and
      have complications so that the onset of the conditions is serious and prevention
      is important. It is necessary to investigate a method that is effective for
      preventing damage for all digestive tracts and the mechanisms of damage must be
      understood for this reason.

PMID- 23855223
TI  - [The onset mechanism of nocturia in the elderly and the possibility of
      ramelteon].
AB  - Nocturia causes sleep disorder and affects not only the fall of QOL but also the
      increase of falling and bone fracture risk, and life convalescence. Therefore,
      among the elderly who are particularly likely to fall down, it is necessary to
      pay attention to them to prevent them from falling down, in addition to their
      treatment for nocturia. On the other hand, it is also necessary to be careful for
      insomnia which the prevalence rate rises by aging, because of their sleep getting
      divided by nocturia. In the examination at our hospital, by the dosage of
      ramelteon to the insomniac patients complicated with nocturia, the increase of
      night bladder capacity and the decrease in number of urination times during night
      were accepted with improvement in insomnia. In addition, adverse event was not
      accepted. From now on, we regard ramelteon as one of the new treatment choices
      for insomniac patients complicated with nocturia.

PMID- 23855224
TI  - [Characteristic and treatment of insomnia in dementia].
AB  - Comorbidity of sleep disturbances in dementia may lead to aggravation of
      cognitive and behavioral problems such as agitation, delirium and wandering in
      night time. Especially, Alzheimer's disease (AD) and frontotemporal dementia
      (FTD) frequently showed a disturbance of the sleep-wake circadian rhythm, on the
      other hand, dementia with Lewy bodies showed REM sleep behavior disorder. This
      disturbance of circadian rhythm is associated with degeneration of responsible
      area for sleep-wake regulation (i.e. suprachiasmatic nucleus: SCN,
      tuberomammillary nucleus: TMN etc.) and decreased melatonin secretion. To prevent
      or treat sleep disturbance in dementia, mixed modality approach with
      pharmacological, physical and social intervention and sleep-wake scheduling is
      needed. Management of the symptom is important for maintaining QOL of not only
      patients themselves but alsotheir caregivers.

PMID- 23855225
TI  - [Clinical characteristics of dappou herb use--disorder patients at the drug
      dependence clinic: a comparison with methamphetamine use-disorder patients].
AB  - BACKGROUND AND PURPOSE: Use of the so-called "dappou herb," a street drug
      typically produced by mixing herbs with synthetic cannabinoid (estimated to be
      the pharmacologically effective ingredient), has recently spread to young people
      in Japan who consider it a new recreational drug. It is not legally regulated
      because no illicit ingredients have been detected in the drug by conventional
      screening tests. It is easily obtained via the Internet or from street vendors.
      As the population abusing this drug has grown, medical problems such as
      psychosis, disturbances of consciousness caused by acute intoxication, and social
      problems such as traffic accidents while under the influence of the drug have
      been increasingly reported. However, few psychiatric symptoms associated with it
      have been identified, and little is known about the psychosocial features of
      abusers. The purpose of the present study was to examine the clinical and
      psychosocial features of outpatients with dappou herb use disorder. METHODS:
      Subjects were 15 male outpatients with dappou herb use disorder who had their
      first medical examination at the Drug Dependence Clinic in the Center Hospital,
      National Center of Neurology and Psychiatry between November 2009 and April 2012.
      The control group comprised 28 age-matched oupatients who had methamphetamine use
      disorder, the most serious drug-related problem in Japan since the 1950s. They
      underwent their first medical examination at the same clinic during the same time
      frame as the study subjects. Clinical and psychosocial information on subjects
      and controls including life histories (educational, occupational, and criminal)
      and clinical information (history of psychoactive substance use, access to the
      mainly abused drug, and DSM-IV diagnoses of substance use disorder and comorbid
      psychiatric disorders) were collected from medical records. These variables were
      compared between the two groups. RESULTS: Analyses revealed differences in the
      life history and clinical characteristics between the subjects and controls. The
      subjects had a higher level of education, more work experience, and a less marked
      history of anti-social behavior other than illicit drug use and possession than
      the controls. However, a clinical history of psychiatric disorders, other than
      substance-related disorders, before drug abuse began was more frequently found in
      the subjects than in the controls. CONCLUSIONS: The present study demonstrates
      that patients with dappou herb use disorder may differ from those with
      methamphetamine use disorder in terms of their background, psychosocial factors,
      and clinical features. These findings suggest that the dappou herb may be
      creating a new type of drug abuser in Japan. Our study also indicates that some
      patients abusing this herb may have been "self-medicating" for symptoms of other
      psychiatric disorders such as depression or anxiety, given that they were more
      likely to have received psychiatric treatment before the start of drug abuse.
      This suggests that the legal regulation of this drug as well as early
      comprehensive intervention for adolescents with mental health problems may be
      required to prevent abuse of the dappou herb. Two limitations of this study
      should be noted. The definition of the dappou herb was vague because the
      ingredients are still unclear. In addition, the sample size of this study was
      very small. However, no studies using larger samples have been reported in Japan.
      Future studies that overcome these limitations are needed.

PMID- 23855226
TI  - [A case of "oneiroid Erlebnisform" influenced by the Great East Japan
      Earthquake].
AB  - Following the Great East Japan Earthquake, although there are a growing number of
      reports on the care of the mental health of victims and supporters, the influence
      of this disaster on individuals with mental disorders has not yet been
      sufficiently clarified. Here, we present a case of "oneiroid Erlebnisform" (Mayer
      Gross, W.), which was influenced by the disaster and relapsed one year after the
      earthquake. We discussed the meaning of this experience and the factors leading
      to recurrence in this case. A male international student in his thirties had
      repeatedly suffered from acute episodic alteration of consciousness. Although he
      had experienced anxiety just after the disaster, he showed improvement during his
      temporary evacuation to Western Japan. Nearly one year after the disaster,
      however, he relapsed, with symptoms characteristic of an oneiroid state. The
      patient stated that he was a fuel rod in the Fukushima nuclear power plant, and
      he then immersed himself in a bathtub full of water in order to avoid meltdown.
      According to ICD-10, the patient was diagnosed with acute polymorphic psychotic
      disorder without symptoms of schizophrenia (F23.0). In addition to the alteration
      of consciousness as the main symptom, since there was no decrease in the level of
      personolity function, it was also considered that the diagnosis of this case was
      atypical psychosis, as proposed by Mitsuda and Hatotani. In the oneiroid
      experience, a variety of visual hallucinations, illusions, and images had
      appeared one after another. We can find catastrophe and salvation as the main
      themes in this state, related to the disaster and nuclear accident. Unloading
      situation after thesis defense, insufficient sleep, poor medication adherence,
      and the increased frequency of earthquakes were important factors in the
      recurrence of the present case. To continue research in Japan after the
      earthquake, the decision was accompanied by anxiety for the patient. One year
      after the earthquake, the patient was trying to enter a doctoral program with
      continued anxiety over the nuclear accident. When the frequency of earthquakes
      increased again, the patient was taking an entrance examination. There is a
      possibility that the anxiety in this situation led to the recurrence. People are
      vulnerable to being exposed to the fear of a disaster even after experiencing
      relief. This situation may increase the risk of recurrence.

PMID- 23855227
TI  - [Mental health activities following the Great East Japan Earthquake in the
      stricken coastal area of Iwate Prefecture].
AB  - Since the Great East Japan Earthquake, many survivors have experienced
      psychological crises because of the immense damage in the coastal area of Iwate
      Prefecture. Mental care teams started activities in March 2011 along the coast of
      Iwate. We employed a mid- to long-term care model. In February 2012, we set up
      the Iwate Mental Care Center and built a long-term support system in Iwate
      Prefecture.

PMID- 23855228
TI  - [Challenges faced by psychiatric services in Miyagi Prefecture after the Great
      East Japan Earthquake].
AB  - Following the Great East Japan Earthquake and Tsunami, the number of patients
      with onset, relapse, and exacerbation of mental disorders was expected to
      increase in Miyagi Prefecture, one of the worst affected areas. The functioning
      of almost all psychiatric hospitals sharply declined or even ceased. This
      situation worsened with traffic congestion and crippled public transportation,
      hindering many patients with psychiatric disorders from accessing mental health
      services. Among them, patients with schizophrenia and related disorders were
      affected the most; some could not reach the hospitals and clinics they had
      regularly visited and had to become new patients of another hospital or clinic.
      Moreover, an increasing number of patients with schizophrenia needed to be
      hospitalized because of acute exacerbations of their disorder, due to the
      experience of the disaster and the consequent drastic changes in their living
      environment Unfortunately, the support system for psychiatric institutions after
      disasters is not yet well structured; the system needs to be rebuilt and
      strengthened in anticipation of future disasters.

PMID- 23855230
TI  - [Disaster relief through inter-professional collaboration --from the standpoint
      of a dietitian].
AB  - The present study examined disaster relief efforts by registered and other
      dietitians following the Great East Japan Earthquake to identify related
      problems. Based on this, the study discussed what is required to develop a
      "disaster relief system through inter-professional collaboration" to cope with
      unanticipated disasters. On March 15, 2011, the Japan Dietetic Association (JDA)
      independently established the "Great East Japan Earthquake relief emergency
      headquarters". The association along with these volunteers was committed to the
      establishment of a system for disaster relief activities with the support of
      Iwate, Miyagi, and Fukushima Prefectures: the number of registered volunteers was
      978; a total of 1,588 dietitians were dispatched; and 602 became involved in
      relief work in the disaster-stricken areas. Registered and other dietitians
      dispatched for disaster relief provided support and home care for evacuation
      centers, elderly facilities, and temporary housing, including dietary and
      nutrition advice and consultation, in cooperation and collaboration with
      administrative dietitians in disaster areas, registered and other dietitians of
      disaster headquarters in disaster-stricken prefectures, the Primary Care for All
      Teams (PCAT) of the Japan Primary Care Association, disaster medical assistance
      teams (DMATs), and volunteer groups. Through the course of the relief activities,
      the following problems were identified: difficulties in responding to varying
      needs in different phases, nutritional measures (population-based and high-risk
      approaches), nutritional disparities among evacuation centers, necessity of a
      section to collect ever-changing information on disaster areas in a comprehensive
      manner, importance of working cooperatively to establish a support system, and
      differences in volunteers' support skills. To facilitate disaster relief through
      inter-professional collaboration, it is necessary for many different
      organizations to understand each other's capabilities in the event of a disaster,
      methods to share problems, needs, and information among them and with new
      members, and the importance of local coordinators.

PMID- 23855229
TI  - [Effects of psychological distress due to the Great East Japan Earthquake,
      tsunami, Fukushima Nuclear Power Plant disasters on psychiatric symptoms in
      patients with mental disorders: observational studies in Tochigi].
AB  - BACKGROUND: The Great East Japan Earthquake and subsequent tsunami of March 11,
      2011 severely damaged a widespread region of northeastern Japan. Consequently,
      the Fukushima Nuclear Power Plant experienced a level seven 3 reactors melted
      down, which released a large amount of radioactive materials into the air. Due to
      the structural damage and radiation leaks, the victims are facing prolonged
      psychological distress. METHODS: Eighty-two subjects with mental disorders who
      made their initial visit during the first 4 months after the earthquake and one
      hundred and ninety-four subjects with mental disorders who had been admitted
      during the first one year after the earthquake to the Jichi Medical University
      Hospital, which is located at the edge of the disaster-stricken region, were
      recruited for this study. Enrolled participants were assessed according to ICD
      10. A questionnaire survey was employed to evaluate the severity of psychological
      distress and total amount of damage. RESULTS: The conditions of 22% of the
      outpatients had been worsened by the psychological distress related to the
      earthquake. Seven percent of the patients who had been hospitalized showed marked
      exacerbations due to the psychological distress associated with the disaster.
      COMMENTS: It is of note that the exacerbation of psychiatric symptoms due to the
      disaster was evident among patients with mental disorders who lived even at the
      edge of the disaster area (i. e., subject to an earthquake intensity of 5 upper
      and 150 km from the Fukushima Nuclear Power Plant). The results suggest that the
      close follow-up of disaster victims with mental disorders is of critical
      importance.

PMID- 23855231
TI  - [Roles and cooperation of medical professionals in natural disasters].
AB  - We have reconsidered the responsibility of occupational therapists who have been
      supporting the victims of the Great East Japan Earthquake. They can analyze
      problems and provide appropriate support for victims with rehabilitation and
      occupational therapy as well as for handicapped people. Support measures that can
      be provided by occupational therapists are as follows: 1) Maintenance and
      improvement of mind and body functions through occupational therapy. 2) Mental
      care. 3) Coordination of social circumstances for elderly and handicapped people.
      4) Maintenance and improvement of ability to perform common activities of daily
      living. 5) Choice and adaptation of welfare equipment. Especially, occupational
      therapy provided with the aim to open victims' minds has an effect on mental
      care. Their mental wounds cannot be healed easily. However, networking and work
      activities play important roles in dealing with daily life. Occupational
      therapists will be expected to provide long-term treatment for victims through
      work activities with professional skills.

PMID- 23855232
TI  - [Cognitive therapy/cognitive behavior therapy for depression].
AB  - Cognitive behavior therapy (CBT) is a structured short-term therapy designed to
      change the patient's negatively distorted cognition. The effectiveness of
      cognitive therapy/cognitive behavior therapy has been increasingly recognized not
      only by professionals and academics but also by the public, and in April, 2010,
      this therapy started to be covered by the national health insurance in Japan. In
      this article, the author described the high-intensity and low-intensity CBT from
      the practical point of view.

PMID- 23855233
TI  - [Recent topics of pediatric ophthalmology].

PMID- 23855234
TI  - [Influence on ocular surface and intraocular pressure of switching from
      preservative-containing to preservative-free carteolol hydrochloride ophthalmic
      solution].

PMID- 23855235
TI  - [Long-term changes in the ratio of exotropia to esotropia patients].
AB  - PURPOSE: To detect the long-term changes in the ratio of exotropia to esotropia
      in Japanese patients. METHODS: The published annual reports of 3 children's
      hospitals in Japan were reviewed with respect to the number of new patients
      diagnosed with either exotropia or esotropia. The yearly ratios of exotropia to
      esotropia were calculated from the past 30-year data. The ratios were analyzed by
      using regression analysis to determine the long-term variability. RESULTS: The
      ratio of exotropia to esotropia has increased in a parallel manner from less than
      1.0 to nearly 2.0 in each of the 3 hospitals. CONCLUSIONS: This gradual increase
      in the ratio might be attributed to the increasing number of exotropic children
      who consult a doctor according to the level of development in health care, or
      might be the result of declining occurrence of accommodative esotropia along with
      the decreasing number of hyperopic children. Further studies are required to
      determine the reason for this tendency.

PMID- 23855236
TI  - [A case of atresia of the nasolacrimal passage with cleft lip and palate].
AB  - INTRODUCTION: Congenital nasolacrimal duct obstruction with facial malformation
      may accompany atresia of the nasolacrimal duct. We report a case of congenital
      bony obstruction of the nasolacrimal duct with cleft lip and palate. CASE: A 2
      year-old boy with obstruction of both lacrimal system. Computed tomography (CT)
      showed lacrimal system aplasia on the right side, and bony obstruction of the
      nasolacrimal duct on the left side. The patient had a history of cleft lip and
      palate. We performed external dacryocystorhinostomy (EX-DCR) at 6 years of age
      because he developed dacryocystitis. We performed EX-DCR again at 8 years of age
      and endonasal DCR (EN-DCR) at 9 years of age due to recurrence. At the time of
      writing, 6 years after the last surgery, his postoperative course is excellent.
      CONCLUSIONS: Epiphora with cleft lip and palate may suggest the possibility of
      the atresia of the nasolacrimal duct. Congenital bony obstruction of the
      nasolacrimal duct with facial malformation may recur postoperatively after DCR
      due to nasal hypoplasia, which should be followed up for a long period.

PMID- 23855237
TI  - [A case of supernumerary caruncle].

PMID- 23855238
TI  - [Guidelines for the clinical management of infectious keratitis (2nd edition)].

PMID- 23855239
TI  - [Poisoning by accidental ingestion of poisonous plants].

PMID- 23855240
TI  - [Aconite poisoning].

PMID- 23855241
TI  - [Plant poisoning in Japan].

PMID- 23855242
TI  - [Design of a detector tube for screening organophosphorus pesticides].

PMID- 23855243
TI  - [Pharmacokinetics].

PMID- 23855244
TI  - [Practical analysis of toxic substances useful for clinical toxicology (1). An
      announcement about the resumption of the committee report of analytical
      toxicology].

PMID- 23855245
TI  - [Practical analysis of toxic substances useful for clinical toxicology (2).
      aconitine alkoloids].

PMID- 23855246
TI  - [N-acetylcysteine].

PMID- 23855247
TI  - [Abnormal lung uptake of 123I-BMIPP].
AB  - An eighty-one-year-old male patient with a feeling of chest pressure was admitted
      to our hospital for investigation of the heart. 201T1/123I-BMIPP dual
      scintigraphy was performed and multiple uptakes of 123I-BMIPP were detected in
      the lung, but not of 201T1. His chest X-ray and chest CT showed no abnormal
      lesions in the corresponding regions. There have been no reports that 123I-BMIPP
      accumulate in the lung. The possible cause of the lung uptake was embolism from
      aggregated 123I-BMIPP due to cold tempetatures.

PMID- 23855248
TI  - [Survey questionnaire of pediatric nuclear medicine examinations in 14 Japanese
      institutes].
AB  - Under the auspices of the Japanese Society of Pediatric Nuclear Medicine, an
      annual aggregate from a 5-year period, 2007 to 2011, of a survey questionnaire of
      pediatric nuclear medicine examinations performed at 14 institutes in the Kanto
      region was conducted. The subjects were pediatric patients 15 years old or
      younger. The survey questions included the determination method for administered
      dose of radiopharmaceuticals, the items examined and number of examinations. Of
      14 institutes, 11 determined administered doses using the formula: adult dose X
      (age +1) / (age+7), while the remaining 3 used the adult dose as the maximum dose
      and used a conversion formula based on age and physical condition. In 2011, in a
      total of 3,884 pediatric patients, renoscintigraphy accounted for 41.5%, brain
      14.4%, pulmonary scintigraphy 12.9%, oncology 9.0%, hepatobiliary scintigraphy
      6.3%, gastrointestinal scintigraphy 4.8%, musculoskeletal scintigraphy 4.3%,
      cardiology 2.5%, and other 4.9% of all nuclear medicine examinations. Pediatric
      nuclear medicine examinations in general hospitals accounted for only 3.4% of all
      examinations. A similar trend was observed in previous years. Since pediatric
      patients have a longer reproductive term and higher sensitivity to radiation
      exposure, pediatric nuclear medicine requires a strict selection of appropriate
      studies and administered dose. These results show the current practice and would
      warrant further consideration.

PMID- 23855249
TI  - How automation helps steer the revenue cycle process.
AB  - If there's one aspect of healthcare that's omnipresent - that is connected in
      some way to virtually every component of the medical trade - it's the revenue
      cycle; and vendors' solutions to manage it are as varied as the experts we
      queried on this topic. The revenue cycle actually touches on nearly everything
      related to healthcare - from the time a patient books an appointment with a
      healthcare facility, until the patient and insurance company provide final
      payments for services rendered to the healthcare provider. Over the past several
      decades, software programs and computers have replaced ledger books and
      calculators. And while the goal of revenue cycle management (RCM) remains
      essentially the same, healthcare reform will make this process infinitely more
      complex, due to reduced reimbursements and the onset of ICD-10 in October 2014.
      Additionally, reimbursement will be tied to quality, rather than quantity.
      According to an Information Week article by Ken Terry, outsourcing of billing and
      collections continues to grow, "because hospitals and physician groups are not
      very good at these non-core tasks." Think writers and math: I know a great many
      writers, including yours truly, who possess truly weak math skills. Granted, both
      skills involve opposite brain hemispheres - different parts of the brain. But
      what may be even more important is the fact that math is not generally an
      integral component of the main function of writing. A similar situation exists in
      healthcare facilities; just replace writing with providing care for people. A
      2012 Black Book Rankings survey states 96 percent of organizations are in the
      process of acquiring several crucial accountable care organization (ACO) data
      solutions, including clinical decision support, RCM, health information exchange
      (HIEs), electronic health records (EHRs), e-prescribing, data center security and
      storage solutions, business intelligence and care coordination management. So
      it's clear that RCM will continue to remain a top-of-mind issue as we see how
      healthcare reform plays out. Here's what our select group of experts had to say
      about how automation helps to steer the revenue cycle process.

PMID- 23855250
TI  - Critical to care.

PMID- 23855251
TI  - Transitioning to a vendor-neutral image archive.

PMID- 23855252
TI  - Enlisting automation in the fight against nightmare bacteria.

PMID- 23855253
TI  - Asset management as a tool to improve patient care.

PMID- 23855254
TI  - The path to enterprise locating.

PMID- 23855255
TI  - How to maintain security in the cloud. Seven factors to consider.

PMID- 23855256
TI  - Longitudinal investigation of source memory reveals different developmental
      trajectories for item memory and binding.
AB  - The present study used a cohort-sequential design to examine developmental
      changes in children's ability to bind items in memory during early and middle
      childhood. Three cohorts of children (aged 4, 6, or 8 years) were followed
      longitudinally for 3 years. Each year, children completed a source memory
      paradigm assessing memory for items and binding. Results suggest linear increases
      in memory for individual items (facts or sources) between 4 and 10 years of age
      but that memory for correct fact/source combinations (indicative of binding)
      showed accelerated rates of change between 5 and 7 years. Taken together, these
      results suggest differences exist in developmental trajectories between the
      development of memory processes underlying successful item memory and processes
      underlying binding. Implications of these findings are discussed in relation to
      longitudinal research examining autobiographical memory.

PMID- 23855257
TI  - Development of coordination in time estimation.
AB  - How to best characterize cognitive development? The claim put forward in this
      article is that development is the improvement of a kind of coordination among a
      variety of factors. To determine the development of coordination in a cognitive
      task, children between 4 and 12 years of age and adults participated in a time
      estimation task: They had to press a button every time they thought a short time
      interval had passed. The resulting data series of estimated time intervals was
      then subjected to a set of fractal analyses to quantify coordination in terms of
      its degree of "rigidity" (very highly integrated) vs. "looseness" (poorly
      integrated). Results show a developmental trajectory toward pink-noise patterns,
      suggesting that cognitive development progresses from a very loose, poorly
      integrated coordination of factors toward a pattern that expresses more
      integration, perhaps due to an optimization of constraints, that allows for a
      more stable coordination.

PMID- 23855259
TI  - Is the association between children's baby video viewing and poor language
      development robust? A reanalysis of Zimmerman, Christakis, and Meltzoff (2007).
AB  - Zimmerman, Christakis, and Meltzoff (see record 2007-18340-001) reported that
      exposure to Baby Einstein videos was negatively associated with language
      development. The current study uses the Zimmerman et al. (2007) data set to
      replicate and extend the original analyses. Caregivers of 392 children aged 6 to
      16 months and 358 children aged 17 to 27 months reported on media exposure,
      language development, and control variables related to child/parent interaction
      and demographic characteristics. Results indicated that exposure to baby videos
      could be construed as positive, neutral, or negative depending upon the
      statistical analysis. The effect size estimates were generally negligible across
      analyses. Exposure to educational programming tended to be positively related to
      language development. Infants exposed to no media actually had lower levels of
      language development compared to infants with some exposure. Given these results,
      the Zimmerman et al. (2007) data set does not permit strong inferences about a
      connection between exposure to media and language development in young children.
      These results also highlight recent concerns over methodological flexibility and
      the possibility of increased Type I errors (false positives) in the psychological
      literature.

PMID- 23855258
TI  - Early handedness in infancy predicts language ability in toddlers.
AB  - Researchers have long been interested in the relationship between handedness and
      language in development. However, traditional handedness studies using single age
      groups, small samples, or too few measurement time points have not capitalized on
      individual variability and may have masked 2 recently identified patterns in
      infants: those with a consistent hand-use preference and those with an
      inconsistent preference. In this study, we asked whether a consistent infant hand
      use preference is related to later language ability. We assessed handedness in 38
      children at monthly intervals from 6-14 months (infant visits) and again from 18
      24 months (toddler visits). We found that consistent right-handedness during
      infancy was associated with advanced language skills at 24 months, as measured by
      the Bayley Scales of Infant and Toddler Development (Bayley-III; Bayley, 2006).
      Children who were not lateralized as infants but who became right-handed or left
      handed as toddlers had typical language scores. Neither timing nor direction of
      lateralization was related to cognitive or general motor skills. This study
      builds on previous literature linking right-handedness and language during the
      first 2 years of life.

PMID- 23855260
TI  - Simple strategy for producing superhydrophobic nanocomposite coatings in situ on
      a building substrate.
AB  - Numerous superhydrophobic materials have been developed in recent years by using
      a combination of two strategies: reducing the surface free energy and roughening
      the surface. Most of these procedures have the serious drawback of involving
      tedious multistage processes, which prevent their large-scale application, such
      as on the external stone and similar material surfaces of buildings exposed to
      the weather. This paper describes an innovative synthesis route for producing
      superhydrophobic surface coatings. The coating can even be produced, outdoors, on
      the building by a low-cost process. We demonstrate that the addition of silica
      nanoparticles to a mixture of organic and inorganic silica oligomers in the
      presence of a surfactant produces a coating of closely packed particles. The
      effect of this is to trap air beneath the water droplets, thus significantly
      minimizing the contact area between droplet and surface. The organic component
      reduces the surface free energy of the material, resulting in a high static
      contact angle. This has the effect of repelling water because the water droplets
      that form simply roll rapidly down the coated surface. The surfactant plays a
      valuable role, acting as a sol-gel transition catalyst and, by coarsening the
      pore structure of the gel network, prevents the coating material from cracking. 

PMID- 23855261
TI  - Metabolism and disposition of the dipeptidyl peptidase IV inhibitor teneligliptin
      in humans.
AB  - 1. The absorption, metabolism and excretion of teneligliptin were investigated in
      healthy male subjects after a single oral dose of 20 mg [(14)C]teneligliptin. 2.
      Total plasma radioactivity reached the peak concentration at 1.33 h after
      administration and thereafter disappeared in a biphasic manner. By 216 h after
      administration, >=90% of the administered radioactivity was excreted, and the
      cumulative excretion in the urine and faeces was 45.4% and 46.5%, respectively.
      3. The most abundant metabolite in plasma was a thiazolidine-1-oxide derivative
      (designated as M1), which accounted for 14.7% of the plasma AUC (area under the
      plasma concentration versus time curve) of the total radioactivity. The major
      components excreted in urine were teneligliptin and M1, accounting for 14.8% and
      17.7% of the dose, respectively, by 120 h, whereas in faeces, teneligliptin was
      the major component (26.1% of the dose), followed by M1 (4.0%). 4. CYP3A4 and
      FMO3 are the major enzymes responsible for the metabolism of teneligliptin in
      humans. 5. This study indicates the involvement of renal excretion and multiple
      metabolic pathways in the elimination of teneligliptin from the human body.
      Teneligliptin is unlikely to cause conspicuous drug interactions or changes in
      its pharmacokinetics patients with renal or hepatic impairment, due to a balance
      in the elimination pathways.

PMID- 23855262
TI  - Study on hemostatic activities of the rhizome of Paris bashanensis.
AB  - CONTEXT. Paris bashanensis Wang et Tang (Liliaceae) is widely used in traditional
      Chinese medicine for the treatment of injuries, fractures and hemorrhage in Hubei
      and Sichuan Province. OBJECTIVE: The n-BuOH extract of Paris bashanensis was
      investigated for hemostatic activity and chemical constituents in order to
      provide a basis for the application in folk use. MATERIALS AND METHODS: The n
      BuOH extract of P. bashanensis was divided into three eluents (30, 50 and 70%
      EtOH) by macroporous adsorptive resin D101. The bleeding time of breaking tail
      hemostasis and clotting time of capillary and slide method in mice were used
      extensively to screen the hemostasis properties after repetitive administration
      of these three fractions (100 mg/kg, 50 mg/kg) for 5 days (total of 5 times, once
      per day). The chemical compounds were analyzed by HPLC-UV. RESULTS: The
      inhibition rates in the bleeding time of 70, 50 and 30% n-BuOH ext. were 45, 32
      and 21%, respectively. Using the slide method the decreasing rate of the clotting
      time of 70, 50 and 30% n-BuOH ext. were 71, 65 and 32% and in the experiment of
      capillary method, the inhibition rates were 43, 31 and 24%, respectively. A total
      of 70% n-BuOH ext. showed a high content of the pennogenin-type saponins by HPLC
      UV. DISCUSSION AND CONCLUSIONS: The 70% n-BuOH ext. of P. bashanensis was found
      to contain high levels of pennogenin saponins, which may lead to a higher
      hemostatic activity. Combined with the hemostatic test, P. bashanensis could be
      used as a resource of hemostatic drug.

PMID- 23855263
TI  - Synergistic effect in carbon coated LiFePO4 for high yield spontaneous grafting
      of diazonium salt. Structural examination at the grain agglomerate scale.
AB  - Molecular grafting of p-nitrobenzene diazonium salt at the surface of (Li)FePO4
      based materials was thoroughly investigated. The grafting yields obtained by
      FTIR, XPS, and elemental analysis for core shell LiFePO4-C are found to be much
      higher than the sum of those associated with either the LiFePO4 core or the
      carbon shell alone, thereby revealing a synergistic effect. Electrochemical, XRD,
      and EELS experiments demonstrate that this effect stems from the strong
      participation of the LiFePO4 core that delivers large amounts of electrons to the
      carbon substrate at a constant energy, above the Fermi level of the diazonium
      salt. Correspondingly large multilayer anisotropic structures that are associated
      with outstanding grafting yields could be observed from TEM experiments. Results
      therefore constitute strong evidence of a grafting mechanism where homolytic
      cleavage of the N2(+) species occurs together with the formation and grafting of
      radical nitro-aryl intermediates. Although the oxidation and concomitant Li
      deintercalation of LiFePO4 grains constitute the main driving force of the
      functionalization reaction, EFTEM EELS mapping shows a striking lack of spatial
      correlation between grafted grains and oxidized ones. 

PMID- 23855264
TI  - Four-part choral synthesis system for investigating intonation in a cappella
      choral singing.
AB  - Accurate tuning is an important aspect of singing in harmony in the context of a
      choir or vocal ensemble. Tuning and 'pitch drift' are concerning factors in
      performance for even the most accomplished professional choirs when singing a
      cappella (unaccompanied). In less experienced choirs tuning often lacks
      precision, typically because individual singers have not developed appropriate
      listening skills. In order to investigate accuracy of tuning in ensemble singing
      situations, a chorally appropriate reference is required against which frequency
      measurements can be made. Since most basic choral singing involves chords in four
      parts, a four-part reference template is used in which the fundamental
      frequencies of the notes in each chord can be accurately set. This template can
      now be used in experiments where three of the reference parts are tuned in any
      musical temperament (tuning system), in this case equal and just temperaments,
      and played over headphones to a singer to allow her/his tuning strategy to be
      investigated. This paper describes a practical implementation of a four-part
      choral synthesis system in Pure Data (Pd) and its use in an investigation of
      tuning of notes by individual singers using an exercise originally written to
      explore pitch drift in a cappella choral singing.

PMID- 23855265
TI  - Evidence-based paramedic models of care to reduce unnecessary emergency
      department attendance--feasibility and safety.
AB  - BACKGROUND: As demand for Emergency Department (ED) services continues to exceed
      increases explained by population growth, strategies to reduce ED presentations
      are being explored. The concept of ambulance paramedics providing an alternative
      model of care to the current default 'see and transport to ED' has intuitive
      appeal and has been implemented in several locations around the world. The
      premise is that for certain non-critically ill patients, the Extended Care
      Paramedic (ECP) can either 'see and treat' or 'see and refer' to another primary
      or community care practitioner, rather than transport to hospital. However, there
      has been little rigorous investigation of which types of patients can be safely
      identified and managed in the community, or the impact of ECPs on ED attendance.
      METHODS/DESIGN: St John Ambulance Western Australia paramedics will indicate on
      the electronic patient care record (e-PCR) of patients attended in the Perth
      metropolitan area if they consider them to be suitable to be managed in the
      community. 'Follow-up' will examine these patients using ED data to determine the
      patient's disposition from the ED. A clinical panel will then develop a protocol
      to identify those patients who can be safely managed in the community. Paramedics
      will then assess patients against the derived ECP protocols and identify those
      deemed suitable to 'see and treat' or 'see and refer'. The ED disposition (and
      other clinical outcomes) of these 'ECP protocol identified' patients will enable
      us to assess whether it would have been appropriate to manage these patients in
      the community. We will also 'track' re-presentations to EDs within seven days of
      the initial presentation. This is a 'virtual experiment' with no direct
      involvement of patients or changes in clinical practice. A systems modelling
      approach will be used to assess the likely impact on ED crowding. DISCUSSION: To
      date the efficacy, cost-effectiveness and safety of alternative community-based
      models of emergency care have not been rigorously investigated. This study will
      inform the development of ECP protocols through the identification of types of
      patient presentation that can be considered both safe and appropriate for
      paramedics to manage in the community.

PMID- 23855266
TI  - Antitumor activity of 2-hydroxycinnamaldehyde for human colon cancer cells
      through suppression of beta-catenin signaling.
AB  - The antiproliferative and antitumor activities of 2-hydroxycinnamaldehyde (1), a
      phenylpropanoid isolated from the bark of Cinnamomum cassia, were investigated
      using human colorectal cancer cells. Compound 1 exhibited antiproliferative
      effects in HCT116 colon cancer cells, accompanied by modulation of the Wnt/beta
      catenin cell signaling pathway. This substance was found also to inhibit beta
      catenin/T-cell factor (TCF) transcriptional activity in HEK293 cells and HCT116
      colon cancer cells. Further mechanistic investigations in human colon cancer
      cells with aberrantly activated Wnt/beta-catenin signaling showed that 1
      significantly suppressed the binding of beta-catenin/TCF complexes to their
      specific genomic targets in the nucleus and led to the down-regulation of Wnt
      target genes such as c-myc and cyclin D1. In an in vivo xenograft model, the
      intraperitoneal administration of 1 (10 or 20 mg/kg body weight, three
      times/week) for four weeks suppressed tumor growth in athymic nude mice implanted
      with HCT116 colon cancer cells significantly, without any apparent toxicity. In
      an ex vivo biochemical analysis of the tumors, compound 1 was also found to
      suppress Wnt target genes associated with tumor growth including beta-catenin, c
      myc, cyclin D1, and survivin. The suppression of the Wnt/beta-catenin signaling
      pathway is a plausible mechanism of action underlying the antiproliferative and
      antitumor activity of 1 in human colorectal cancer cells. 

PMID- 23855267
TI  - Role of physical activity in the treatment of nonalcoholic fatty liver disease in
      children and adolescents.
AB  - Currently, nonalcoholic fatty liver disease (NAFLD) is the most frequent liver
      abnormality observed in obese children and adolescents. A strong body of evidence
      suggests that increased liver fat is significantly associated with visceral
      adiposity, metabolic syndrome, and insulin resistance in obese children and
      adolescents. Diet and exercise are generally recommended to treat obese youth
      with NAFLD as they do not carry side effects and confer multiple cardiometabolic
      benefits. Studies in adult populations report a beneficial effect of regular
      physical activity on reducing liver fat. In children and adolescents, available
      data show that weight loss induced by increasing physical activity and calorie
      restriction is beneficial to reduce liver fat and associated health risk factors
      such as insulin resistance and dyslipidemia. Currently, evidence regarding the
      independent effects of regular exercise alone (e.g., without calorie restriction)
      on NAFLD are unclear. Additionally, there is no data regarding the optimal
      exercise regimen (e.g., type, dose, intensity) that should be prescribed for
      reducing NAFLD in children and adolescents. The purpose of this review is to
      examine the role of physical activity on NAFLD in children and adolescents. 

PMID- 23855268
TI  - Caffeine and glucose homeostasis during rest and exercise in diabetes mellitus.
AB  - Caffeine is a substance that has been used in our society for generations,
      primarily for its effects on the central nervous system that causes wakefulness.
      Caffeine supplementation has become increasingly more popular as an ergogenic aid
      for athletes and considerable scientific evidence supports its effectiveness.
      Because of their potential to alter energy metabolism, the effects of coffee and
      caffeine on glucose metabolism in diabetes have also been studied both
      epidemiologically and experimentally. Predominantly targeting the adenosine
      receptors, caffeine causes alterations in glucose homeostasis by decreasing
      glucose uptake into skeletal muscle, thereby causing elevations in blood glucose
      concentration. Caffeine intake has also been proposed to increase symptomatic
      warning signs of hypoglycemia in patients with type 1 diabetes and elevate blood
      glucose levels in patients with type 2 diabetes. Other effects include potential
      increases in glucose counterregulatory hormones such as epinephrine, which can
      also decrease peripheral glucose disposal. Despite these established
      physiological effects, increased coffee intake has been associated with reduced
      risk of developing type 2 diabetes in large-scale epidemiological studies. This
      review paper highlights the known effects of caffeine on glucose homeostasis and
      diabetes metabolism during rest and exercise. 

PMID- 23855269
TI  - Effect of high-intensity interval exercise on basal triglyceride metabolism in
      non-obese men.
AB  - A single bout of high-intensity interval aerobic exercise has been shown to
      produce the same or greater metabolic benefits as continuous endurance exercise
      with considerably less energy expenditure, but whether this applies to very low
      density lipoprotein (VLDL) metabolism is not known. We sought to examine the
      effect of a single bout of high-intensity interval aerobic exercise on basal VLDL
      triglyceride (TG) kinetics 14 and 48 h after exercise cessation to determine the
      acute and time-dependent effects of this type of exercise on VLDL-TG metabolism.
      Eight healthy sedentary men (age, 23.6 +/- 6.1 years; body mass index, 23.1 +/-
      2.2 kg.m(-2), peak oxygen consumption (VO2peak), 36.3 +/- 5.5 mL.kg(-1).min(-1))
      participated in three stable isotopically labeled tracer infusion studies: (i) 14
      h and (ii) 48 h after a single bout of high-intensity aerobic interval exercise
      (60% and 90% of VO2peak in 4 min intervals for a total of 32 min; gross energy
      expenditure ~500 kcal) and (iii) after an equivalent period of rest, in random
      order. Fasting plasma VLDL-TG concentration was 20% lower at 14 h (P = 0.046) but
      not at 48 h (P = 1.000) after exercise compared with the resting trial. VLDL-TG
      plasma clearance rate increased by 21% at 14 h (P < 0.001) but not at 48 h (P =
      0.299) after exercise compared with rest, whereas hepatic VLDL-TG secretion rate
      was not different from rest at any time point after exercise. We conclude that
      high-intensity interval exercise reduces fasting plasma VLDL-TG concentrations in
      non-obese men the next day by augmenting VLDL-TG clearance, just like a single
      bout of continuous endurance exercise. This effect is short-lived and abolished
      by 48 h after exercise. 

PMID- 23855270
TI  - Perceived lactose intolerance in adult Canadians: a national survey.
AB  - Although double-blind studies show that lactose-intolerant individuals can
      consume moderate quantities of milk products without perceptible symptoms, many
      who perceive that they are lactose intolerant limit or avoid milk products,
      potentially compromising calcium and vitamin D intakes. Adult Canadians are at
      risk of inadequate intakes of these nutrients, but no data exist on the
      prevalence, correlates, and potential impact of perceived lactose intolerance
      among Canadians. To address this, a Web-based survey of a population
      representative sample of 2251 Canadians aged >=19 years was conducted. Overall,
      16% self-reported lactose intolerance. This was more common in women (odds ratio
      (OR), 1.84; 95% CI, 1.46-2.33) and in nonwhites (OR, 1.79; 95% CI, 1.24-2.58) and
      less common in those >50 years of age (OR, 0.71; 95% CI, 0.56-0.90) and in those
      completing the survey in French (OR, 0.74; 95% CI, 0.56-0.99). Those with self
      reported lactose intolerance had lower covariate-adjusted milk product and
      alternative intakes (mean +/- SE; 1.40 +/- 0.08 servings.day(-1) vs. 2.33 +/-
      0.03 servings.day(-1), p < 0.001). A greater proportion used supplements
      containing calcium (52% vs. 37%, p < 0.001) and vitamin D (58% vs. 46%, p <
      0.001), but calcium intakes from the combination of milk products, alternatives,
      and supplements were lower (739 +/- 30 mg.day(-1) vs. 893 +/- 13 mg.day(-1), p <
      0.0001). Variation in self-reported lactose intolerance by sex, age, and language
      preference was unexpected and suggests that some groups may be more vulnerable to
      the perception that they are lactose intolerant. Regardless of whether lactose
      intolerance is physiologically based or perceptual, education is required to
      ensure that calcium intakes are not compromised. 

PMID- 23855271
TI  - Branched-chain amino acids alleviate nonalcoholic steatohepatitis in rats.
AB  - Nonalcoholic steatohepatitis (NASH) is a prevalent disease in countries around
      the world. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine
      cannot be synthesized by the body and have been shown to promote muscle buildup;
      thus, it is logical to suggest that BCAAs can reduce fat deposition in the body.
      We used gonadectomized rats fed a high-fat diet to investigate the effects of
      BCAAs on lipid metabolism over an 8-week experimental period. Body composition,
      tissue histology, plasma lipid indices, and hormone levels were examined. We
      demonstrated that the body weights of rats were not significantly decreased but
      the mesenteric fat was significantly decreased (p < 0.05) in BCAA-treated rats.
      In addition, BCAAs decreased plasma lipid levels and fat deposition in the liver.
      At week 4, when the untreated rats displayed macrovesicular steatosis, BCAA
      treated rats had only macrovesicular droplets in their hepatocytes. At week 8,
      when the untreated rat livers displayed profound inflammation and cirrhosis, BCAA
      treated rat livers remained in the macrovesicular stage of steatosis. BCAAs
      induced higher blood glucose and plasma insulin levels (p < 0.05). BCAAs also
      improved liver blood flow by increasing mean arterial blood pressure and
      decreasing portal pressure, which helped delay the change in blood flow pattern
      to that of cirrhosis. BCAAs also induced the skeletal muscle to express higher
      levels of branched-chain alpha-keto acid dehydrogenase E1alpha, which indicates
      an enhanced metabolic capacity of BCAAs in muscle tissue. This study clearly
      demonstrates the effects of BCAAs on the amelioration of fat deposition in rats
      fed a high-fat diet. 

PMID- 23855272
TI  - Protein-energy malnutrition induces an aberrant acute-phase response and modifies
      the circadian rhythm of core temperature.
AB  - Protein-energy malnutrition (PEM), present in 12%-19% of stroke patients upon
      hospital admission, appears to be a detrimental comorbidity factor that impairs
      functional outcome, but the mechanisms are not fully elucidated. Because ischemic
      brain injury is highly temperature-sensitive, the objectives of this study were
      to investigate whether PEM causes sustained changes in temperature that are
      associated with an inflammatory response. Activity levels were recorded as a
      possible explanation for the immediate elevation in temperature upon introduction
      to a low protein diet. Male, Sprague-Dawley rats (7 weeks old) were fed a control
      diet (18% protein) or a low protein diet (PEM, 2% protein) for either 7 or 28
      days. Continuous core temperature recordings from bioelectrical sensor
      transmitters demonstrated a rapid increase in temperature amplitude, sustained
      over 28 days, in response to a low protein diet. Daily mean temperature rose
      transiently by day 2 (p = 0.01), falling to normal by day 4 (p = 0.08), after
      which mean temperature continually declined as malnutrition progressed. There
      were no alterations in activity mean (p = 0.3) or amplitude (p = 0.2) that were
      associated with the early rise in mean temperature. Increased serum alpha-2
      macroglobulin (p < 0.001) and decreased serum albumin (p <= 0.005) combined with
      a decrease in serum alpha-1-acid glycoprotein (p < 0.001) suggest an atypical
      acute-phase response. In contrast, a low protein diet had no effect on the
      signaling pathway of the pro-inflammatory transcription factor, NFkappaB, in the
      hippocampus. In conclusion, PEM induces an aberrant and sustained acute-phase
      response coupled with long-lasting effects on body temperature. 

PMID- 23855273
TI  - Influence of netball-based exercise on energy intake, subjective appetite and
      plasma acylated ghrelin in adolescent girls.
AB  - This study explored 5-day regulation of exercise-induced energy expenditure,
      energy intake, and hormonal appetite, via acylated ghrelin, after acute exercise.
      Using a randomized crossover design, 10 female adolescents (13-15 years old)
      completed two 7-day treatment weeks (2 days of maintenance, 1 day of treatment,
      and a 4-day follow-up), interspersed with a 1-week period. On day 3, 47 min of
      netball-based exercise or sedentary activity was imposed with a test meal 1 h
      later. Measures of energy expenditure, subjective appetite, test meal energy
      intake, plasma acylated ghrelin, insulin, and glucose were taken during this
      period. Energy intake compensation for the exercise period was calculated. Four
      day follow-up measures were daily subjective appetite, energy intake, energy
      expenditure, and energy balance. Girls felt more full 20 min during the netball
      based exercise bout compared with sedentary activity (87 +/- 15 mm vs. 75 +/- 24
      mm). An energy intake compensation of 27% was identified for the netball-based
      exercise. Compared with immediately before exercise or sedentary activity, plasma
      acylated ghrelin was elevated 45 min after netball (103.8 +/- 56.9 pg.mL(-1) vs.
      85.7 +/- 26.9 pg.mL(-1); n = 7) and sedentary activity (98.2 +/- 27.1 pg.mL(-1)
      vs. 60.8 +/- 33.5 pg.mL(-1); n = 7) but not different between treatments.
      Adolescent girls (13-15 years old) only partially compensated for the netball
      based exercise-induced energy expenditure. The effect of exercise on appetite
      needs to be further explored in adolescents, whereby nutritional behaviour is
      tracked for more than 1 week to investigate full compensation for acute exercise.

PMID- 23855274
TI  - Mammalian target of rapamycin pathway is up-regulated by both acute endurance
      exercise and chronic muscle contraction in rat skeletal muscle.
AB  - This study examined changes in the expression of translation initiation
      regulatory proteins and mRNA following both an acute bout of endurance exercise
      and chronic muscle contractile activity. Female Sprague Dawley rats ran for 2 h
      at 15 m.min(-1) followed by an increase in speed of 5 m.min(-1) every 5 min until
      volitional fatigue. The red gastrocnemius muscle was harvested from nonexercised
      animals (control; n = 6) and from animals that exercised either immediately after
      exercise (n = 6) or following 3 h of recovery from exercise (n = 6). Compared
      with control, ribosomal protein S6 (rpS6) mRNA was elevated (p < 0.05) at both 0
      h (+32%) and 3 h (+47%). Both a catalytic subunit of eukaryotic initiation factor
      2B (eIF2Bepsilon) (+127%) and mammalian target of rapamycin (mTOR) mRNA (+44%)
      were increased at 3 h, compared with control. Phosphorylation of mTOR (+40%) and
      S6 kinase 1 (S6K1) (+266%) were increased immediately after exercise (p < 0.05).
      Female Sprague Dawley rats also underwent chronic stimulation of the peroneal
      nerve continuously for 7 days. The red gastrocnemius muscle was removed 24 h
      after cessation of the stimulation. Chronic muscle stimulation increased (p <
      0.05) mTOR protein (+74%), rpS6 (+31%), and eukaryotic initiation factor 2alpha
      (+44%, p = 0.069), and this was accompanied by an increase in cytochrome c
      (+31%). Increased resting phosphorylation was observed for rpS6 (+51%) (p < 0.05)
      but not for mTOR or eukaryotic initiation factor 4E binding protein 1. These
      experiments demonstrate that both acute and chronic contractile activity up
      regulate the mTOR pathway and mitochondrial content in murine skeletal muscle.
      This up-regulation of the mTOR pathway may increase translation efficiency and
      may also represent an important control point in exercise-mediated mitochondrial
      biogenesis. 

PMID- 23855275
TI  - Fatty acid ethanolamides modulate CD36-mRNA through dietary fatty acid
      manipulation in Syrian Golden hamsters.
AB  - Fatty acids convert to fatty acid ethanolamides which associate with lipid
      signalling, fat oxidation, and energy balance; however, the extent to which
      dietary fatty acids manipulation can impact such control processes through fatty
      acid ethanolamides-related mechanisms remains understudied. The objective was to
      examine the impact of diets containing 6% corn oil, high oleic canola oil,
      docosahexaenoic acid + high oleic canola oil, and fish oil on plasma and organ
      levels of fatty acid ethanolamides, peroxisome proliferator-activated receptor
      alpha regulatory targets, and lipid metabolism in Syrian Golden hamsters. After
      29 days, in plasma, animals that were fed fish oil showed greater (p < 0.05)
      oleoylethanolamide and lower (p < 0.05) arachidonoylethanolamide and
      palmitoylethanolamide levels compared with other groups, while animals fed canola
      oil showed higher (p < 0.05) oleoylethanolamide levels in proximal intestine and
      liver than groups that were fed coin oil and fish oil. The canola oil group
      showed elevated (p < 0.01) fat oxidation (%) and over 3.0-fold higher (p < 0.05)
      hepatic-CD36 expression compared with the corn oil group. Hepatic-lipogenesis was
      lower (p < 0.05) in hamsters that were fed DHA-canola oil compared with the corn
      oil group. To conclude, dietary fatty acids produced shifts in plasma and organ
      levels of arachidonoylethanolamide, oleoylethanolamide, and palmitoylethanolamid,
      which were accompanied by changes in gene expression, lipogenesis, and energy
      expenditure, suggesting mechanisms through which dietary fatty acids influence
      disease risk. 

PMID- 23855276
TI  - Effects of severe caloric restriction from birth on the hearts of adult rats.
AB  - There has been increasing evidence suggesting that a severe caloric restriction
      (SCR) (above 40%) has beneficial effects on the hearts of rats. However, most of
      the reports have focused on the effects of SCR that started in adulthood. We
      investigated the consequences of SCR on the hearts of rats subjected to SCR since
      birth (CR50). From birth to the age of 3 months, CR50 rats were fed 50% of the
      food that the ad libitum group (AL) was fed. Thereafter, a maximal aerobic test
      was performed to indirectly evaluate global cardiovascular function. Indices of
      contractility (+dT/dt) and relaxation (-dT/dt) were analyzed in isolated heart
      preparation, and cardiomyocyte diameter, number, density, and myocardium collagen
      content were obtained through histologic analysis. Ventricular myocytes were
      isolated, using standard methods to evaluate phosphorylated AKT levels, and
      Ca(2+) handling was evaluated with a combination of Western blot analysis,
      intracellular Ca(2+) imaging, and confocal microscopy. CR50 rats exhibited
      increased aerobic performance and cardiac function, as shown by the increase in
      +/-dT/dt. Despite the smaller cardiomyocyte diameter, CR50 rats had an increased
      heart-body weight ratio, increased cardiomyocyte density and number, and similar
      levels of myocardium collagen content, compared with AL rats. AKT was
      hyperphosphorylated in cardiomyocytes from CR50 rats, and there were no
      significant differences in Ca(2+) transient and SERCA2 levels in cardiomyocytes
      between CR50 and AL rats. Collectively, these observations reveal the beneficial
      effects of a 50% caloric restriction on the hearts of adult rats restricted since
      birth, which might involve cardiomyocyte AKT signaling. 

PMID- 23855277
TI  - The effect of walking on cardiorespiratory fitness in adults with knee
      osteoarthritis.
AB  - Walking programs alone or in combination with behavioral interventions have
      proven effective at improving quality of life among older adults with
      osteoarthritis (OA). It is unclear, however, whether the combination of both of
      these treatments is more effective at improving cardiorespiratory fitness in
      older adults with knee OA than a walking program alone or than unsupervised self
      directed walking. In this study, we assessed cardiorespiratory fitness with 3
      programs: a structured supervised community-based aerobic walking program with a
      behavioral intervention (WB; n = 41); a supervised program of walking only (W; n
      = 42); and an unsupervised self-directed walking program (n = 32). We measured
      maximal oxygen uptake (VO2peak), exercise test duration, and workload, heart
      rate, and ventilation at maximum aerobic capacity in older adults with knee OA
      after 6 months of WB, W, or self-directed walking. Overall, VO2peak improved by
      4% in female walkers (+0.9 +/- 2.5 mL O2.kg(-1).min(-1); p < 0.001) and 5% in
      male walkers (+1.3 +/- 2.7 mL O2.kg(-1).min(-1); p < 0.001), and the change in
      fitness was similar with all 3 walking interventions. In conclusion, low- to
      moderate-intensity walking may improve and (or) prevent decrements in
      cardiorespiratory fitness in older adults with OA. This response was comparable
      in supervised walkers with and without a behavioral intervention and in
      unsupervised self-directed walkers. 

PMID- 23855278
TI  - The Visceral Adiposity Index: Relationship with cardiometabolic risk factors in
      obese and overweight postmenopausal women--a MONET group study.
AB  - A recent study suggested visceral adipose index (VAI) as an indicator of adipose
      tissue distribution and function associated with cardiometabolic risk. We aim to
      examine the association between VAI and visceral adipose tissue (VAT), insulin
      sensitivity, and a large panel of associated cardiometabolic risk factors, and to
      determine if changes in VAI after weight loss intervention will reflect changes
      in VAT. We performed a secondary analysis using the data of 99 overweight and
      postmenopausal women that completed a 6-month weight loss program (Montreal
      Ottawa New Emerging Team Study). VAI was calculated according to the equation by
      Amato et al. (2010; Diabetes Care, 33(4):920-922). At baseline, VAI was
      associated with VAT (r = 0.284, p < 0.01) but not with subcutaneous adipose
      tissue (SAT) while body mass index (BMI) and waist circumference (WC) were
      significantly related to both. BMI and WC demonstrated significantly stronger
      predictive value of VAT accumulation (area under the curve = 0.84 and 0.86,
      respectively) than VAI (area under the curve = 0.61; p < 0.01). However, VAT,
      BMI, WC, and VAI were similarly related to fasting insulin and glucose disposal
      rates. After a 6-month weight loss program, VAI decreased significantly and
      similarly in both intervention groups (p < 0.01). In addition, the percentage of
      change in VAI showed the significantly weakest correlation (r = 0.25) with the
      percentage of change in VAT than BMI (r = 0.56; p < 0.01 for r comparisons) and
      was not a significant predictor of interindividual percentage of change in VAT
      while BMI accounted for 33.7%. VAI is a weak indicator of VAT function and did
      not predict changes in VAT after weight loss. Furthermore, this index was not
      superior to BMI or WC. However, VAI is a good indicator of metabolic syndrome. 

PMID- 23855279
TI  - Glycemic response varies between resistance and aerobic exercise in inactive
      males with long-term type 2 diabetes.
AB  - The glycemic response to aerobic exercise is well understood; however, the
      response to resistance exercise is not. Eight inactive males (61.0 +/- 7.2 years)
      with insulin-treated type 2 diabetes randomly completed single sessions of whole
      body resistance exercise or cycling, 7 days apart. There were different 24-h
      glucose responses (p < 0.001) between the resistance exercise and the aerobic
      exercise, with short-term (24-h) impairment of glycemic control following the
      resistance exercise (p = 0.004). Cycling did not reduce glucose concentrations (p
      > 0.05), which contrasts with previous findings. 

PMID- 23855280
TI  - Effect of ambient temperature during acute aerobic exercise on short-term
      appetite, energy intake, and plasma acylated ghrelin in recreationally active
      males.
AB  - Ambient temperature during exercise may affect energy intake regulation. Compared
      with a temperate (20  degrees C) environment, 1 h of running followed by 6 h of
      rest tended to decrease energy intake from 2 ad libitum meals in a hot (30 
      degrees C) environment but increase energy intake in a cool (10  degrees C)
      environment (p = 0.08). Core temperature changes did not appear to mediate this
      trend; whether acylated ghrelin is involved is unclear. Further research is
      warranted to clarify these findings. 

PMID- 23855284
TI  - Adolescents exposed to suicidal behavior of others: prevalence of self-harm and
      associated psychological, lifestyle, and life event factors.
AB  - Exposure to suicidal behavior of others was examined among 3,881 Irish
      adolescents in the Child and Adolescent Self-harm in Europe (CASE) study. One
      third of the sample had been exposed to suicidal behavior, and exposed
      adolescents were eight times more likely to also report own self-harm. Exposed
      adolescents shared many risk factors with those reporting own self-harm. Those
      reporting both exposure and own self-harm presented the most maladaptive profile
      on psychological, life event, and lifestyle domains, but neither anxiety nor
      depression distinguished this group. Exposed adolescents are burdened by a wide
      range of risk factors and in need of support. 

PMID- 23855285
TI  - New drugs and clinical trial design in advanced sarcoma: have we made any
      progress?

PMID- 23855286
TI  - It is time to start active treatment in senior adults with prostate cancer.

PMID- 23855287
TI  - Divergence of host range and biological properties between natural isolate and
      full-length infectious cDNA clone of the Beet mild yellowing virus 2ITB.
AB  - Plant infection by poleroviruses is restricted to phloem tissues, preventing any
      classical leaf rub inoculation with viral RNA or virions. Efficient virus
      inoculation to plants is achieved by viruliferous aphids that acquire the virus
      by feeding on infected plants. The use of promoter-driven infectious cDNA is an
      alternative means to infect plants and allows reverse genetic studies to be
      performed. Using Beet mild yellowing virus isolate 2ITB (BMYV-2ITB), we produced
      a full-length infectious cDNA clone of the virus (named BMYV-EK) placed under the
      control of the T7 RNA polymerase and the Cauliflower mosaic virus 35S promoters.
      Infectivity of the engineered BMYV-EK virus was assayed in different plant
      species and compared with that of the original virus. We showed that in vitro- or
      in planta-derived transcripts were infectious in protoplasts and in whole plants.
      Importantly, the natural aphid vector Myzus persicae efficiently transmitted the
      viral progeny produced in infected plants. By comparing agroinoculation and aphid
      infection in a host range assay, we showed that the engineered BMYV-EK virus
      displayed a similar host range to BMYV-2ITB, except for Nicotiana benthamiana,
      which proved to be resistant to systemic infection with BMYV-EK. Finally, both
      the BMYV-EK P0 and the full-length clone were able to strongly interfere with
      post-transcriptional gene silencing.

PMID- 23855288
TI  - Alcoholic liver disease and pancreatitis: global health problems being addressed
      by the US National Institute on Alcohol Abuse and Alcoholism.
AB  - The review article summarizes the mission of the National Institute on Alcohol
      Abuse and Alcoholism (NIAAA) with focus on the NIAAA's current and future
      research version for alcoholic liver disease and alcoholic pancreatitis. 

PMID- 23855289
TI  - Update on epidemiology of hepatitis B and C in China.
AB  - A high rate of chronic hepatitis B virus (HBV) infection in China is mainly
      caused by perinatal or early childhood transmission. Administration of universal
      HBV vaccination in infants has led to a dramatic decrease in HBV epidemiology,
      with hepatitis B surface antigen (HBsAg) prevalence declining from 9.75% in 1992
      to 7.18% in 2006. The major HBV genotypes are B and C, with B being more
      prevalent in the southern part and C more prevalent in the northern part of
      China. A national survey carried out in 1992 showed that the hepatitis C virus
      (HCV) infection rate was 3.20% in general population in China. After
      implementation of mandatory HCV screening for blood transfusion and other
      precautions to prevent blood-borne disease since 1993, the new cases of HCV
      infection associated with blood or blood product has become very rare. Although
      the anti-HCV prevalence would be much higher in high-risk groups, a survey
      carried in 2006 showed that the anti-HCV prevalence rate was only 0.43% in
      general population. This sharp decline in HCV infection rate was mainly due to
      stringent administration and monitoring of blood donors and blood products, but
      may also be related to the remarkably improved specificity of anti-HCV test. The
      predominant HCV genotype in China is genotype 1b (60-70%), and the host
      interleukin-28b rs12979860 CC genotype is very frequent in Chinese population
      (over 80%).

PMID- 23855290
TI  - Epidemiology of alcoholic and nonalcoholic fatty liver disease in China.
AB  - The prevalence of patients presenting with fatty liver disease (FLD) in China has
      approximately doubled over the past two decades. At present, FLD, which is
      typically diagnosed by imaging, is highly prevalent (~ 27% urban population) in
      China and is mainly related to obesity and metabolic syndrome (MetS). However,
      the percentage of alcoholic liver disease (ALD) among patients with chronic liver
      diseases in clinic is increasing as well, and a synergetic effect exists between
      heavy alcohol drinking and obesity in ALD. Prevalence figures reveal regional
      variations, with a median prevalence of ALD and nonalcoholic FLD (NAFLD) of 4.5%
      and 15.0%, respectively. The prevalence of NAFLD in children is 2.1%, although
      the prevalence increases to 68.2% among obese children. With the increasing
      pandemic of obesity and MetS in the general population, China is likely to harbor
      an increasing reservoir of patients with FLD. The risk factors for FLD resemble
      to those of Caucasian counterparts, but the ethnic-specific definitions of
      obesity and MetS are more useful in assessment of Chinese people. Therefore,
      FLD/NAFLD has become a most common chronic liver disease in China. Public health
      interventions are needed to halt the worldwide trend of obesity and alcohol abuse
      to ameliorate liver injury and to improve metabolic health.

PMID- 23855291
TI  - Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.
AB  - Despite major progress in understanding and managing liver disease in the past 30
      years, it is now among the top 10 most common causes of death globally. Several
      risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption,
      viral infection, gender, immune dysfunction, and medications, acting individually
      or in concert, are known to precipitate liver damage. Viral hepatitis, excessive
      alcohol consumption, and obesity are the major factors causing liver injury.
      Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected
      subjects worldwide are staggering (370 and 175 million, respectively), and of the
      40 million known human immunodeficiency virus positive subjects, 4 and 5 million
      are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading
      causes of end-stage liver disease worldwide and the most common indication for
      liver transplantation in the United States and Europe. In addition, the global
      obesity epidemic that affects up to 40 million Americans, and 396 million
      worldwide, is accompanied by an alarming incidence of end-stage liver disease, a
      condition exacerbated by alcohol. This article focuses on the interactions
      between alcohol, viral hepatitis, and obesity (euphemistically described here as
      the Bermuda Triangle of liver disease), and discusses common mechanisms and
      synergy. 

PMID- 23855292
TI  - Vascular biology of the biliary epithelium.
AB  - Cholangiocytes are involved in a variety of processes essential for liver
      pathophysiology. To meet their demanding metabolic and functional needs, bile
      ducts are nourished by their own arterial supply, the peribiliary plexus. This
      capillary network originates from the hepatic artery and is strictly arranged
      around the intrahepatic bile ducts. Biliary and vascular structures are linked by
      a close anatomic and functional association necessary for liver development,
      normal organ physiology, and liver repair. This strong association is finely
      regulated by a range of angiogenic signals, enabling the cross talk between
      cholangiocytes and the different vascular cell types. This review will briefly
      illustrate the "vascular" properties of cholangiocytes, their underlying
      molecular mechanisms and the relevant pathophysiological settings. 

PMID- 23855293
TI  - Retinoids and their target genes in liver functions and diseases.
AB  - Retinoids have been reported to prevent several kinds of cancers, including
      hepatocellular carcinoma (HCC). Retinoic acid (RA) coupled with retinoic acid
      receptor/retinoid X receptor heterodimer exerts its functions by regulating its
      target genes. We previously reported that transgenic mice, in which RA signaling
      is suppressed in a hepatocyte-specific manner, developed liver cancer at a high
      rate, and that disruption of RA functions led to the increased oxidative stress
      via aberrant metabolisms of lipid and iron, indicating that retinoids play an
      important role in liver pathophysiology. These data suggest that exploring the
      metabolism of retinoids in liver diseases and their target genes provides us with
      useful information to understand the liver functions and diseases. Consequently,
      the altered metabolism of retinoids was observed in liver diseases, including non
      alcoholic fatty liver disease. In this review, we summarize the metabolism of
      retinoids in the liver, highlight the functions of retinoids in HCC, non
      alcoholic fatty liver disease, and alcoholic liver disease, and discuss the
      target genes of RA. Investigation of retinoids in the liver will likely help us
      identify novel therapies and diagnostic modalities for HCC. 

PMID- 23855295
TI  - Tumor microenviroment and hepatocellular carcinoma metastasis.
AB  - The cross talk between tumor cells and the surrounding peritumoral stroma has
      been extensively studied as a dynamic system involving the processes of
      hepatocarcinogenesis, tumor invasion, and metastasis in recent few decades.
      Besides hepatocytes, liver tumor microenvironments are generally classified into
      cellular and noncellular components, including hepatic stellate cells,
      fibroblasts, immune, endothelial, mesenchymal stem cells, together with growth
      factors, cytokines, extracellular matrix, hormone as well as viruses et al. The
      noncellular components manipulate hepatocellular carcinoma invasion and
      metastasis by facilitating epithelial-mesenchymal transition, increasing
      proteolytic activity of matrix metalloproteinases, and regulating antitumor
      immunity, etc. Because the main cause of death in hepatocellular carcinoma
      patients is tumor progression with metastasis, a better understanding of the
      interplay between hepatocytes and their environment during tumor metastasis may
      be helpful for the discovery of novel molecular targets.

PMID- 23855294
TI  - Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and
      carcinogenesis.
AB  - Activation of innate immune systems including Toll-like receptor (TLR) signaling
      is a key in chronic liver disease. Recent studies suggest that gut microflora
      derived bacterial products (i.e. lipopolysaccharide [LPS], bacterial DNA) and
      endogenous substances (i.e. high-mobility group protein B1 [HMGB1], free fatty
      acids) released from damaged cells activate hepatic TLRs that contribute to the
      development of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH) and liver
      fibrosis. The crucial role of TLR4, a receptor for LPS, has been implicated in
      the development of ASH, NASH, liver fibrosis, and hepatocellular carcinoma.
      However, the role of other TLRs, such as TLR2 and TLR9 in chronic liver disease
      remains less clear. In this review, we will discuss the role of TLR2, 4, and 9 in
      Kupffer cells and hepatic stellate cells in the development of ASH, NASH, and
      hepatocarcinogenesis. 

PMID- 23855296
TI  - Vitamin D in liver diseases: from mechanisms to clinical trials.
AB  - Traditionally regarded as a typical vitamin regulating calcium and phosphorus
      homeostasis, vitamin D is now discovered as a highly versatile molecule with
      emerging roles in immunity, cancer, infectious diseases, fibrosis, fatty liver
      diseases, and alcoholic liver diseases. A large body of clinical evidence has
      demonstrated the prevalence and risks of vitamin D deficiency in various chronic
      diseases. Biologically active vitamin D, 1,25-dihydroxylvitamin D3, is
      synthesized in two distinct systems. In addition to the classic two-step
      hydroxylation in the liver and kidneys, 1,25-dihydroxylvitamin D3 can also be
      produced locally by immune cells in response to infection. The bioactive vitamin
      D generated in these two pools apparently functions differently: while the former
      facilitates calcium adsorption and homeostasis, the latter confers immune
      regulation. The immune regulatory functions of vitamin D are demonstrated by
      induction of antimicrobial peptides, suppression of innate immune response,
      induction of Th2 cytokines, and stimulation of T-regulatory T cells. Vitamin D
      deficiency or insufficiency is overwhelmingly associated with viral hepatitis,
      cirrhosis, and fatty liver diseases. Recent clinical trials have shown that
      vitamin D supplements significantly enhance the efficacy of interferon plus
      ribavirin therapy through sustained virological response. A recent study showed
      that 25-dihydroxyvitamin D rather than 1,25-dihydroxyvitamin D could directly
      suppress hepatitis C virus assembly. Moreover, clinical evidence has shown that
      vitamin D deficiency is associated with alcoholic and non-alcoholic fatty liver
      diseases. In this review, we highlight some recent advances in vitamin D
      researches and clinical trails. 

PMID- 23855297
TI  - Hepatoprotective and anti-fibrotic functions of interleukin-22: therapeutic
      potential for the treatment of alcoholic liver disease.
AB  - Interleukin-22 (IL-22) plays a key role in promoting antimicrobial immunity and
      tissue repair at barrier surfaces by binding to the receptors IL-22R1, which is
      generally thought to be expressed exclusively in epithelial cells, and IL-10R2.
      Our laboratory previously demonstrated that IL-22 plays an important role in
      ameliorating liver injury in many rodent models by targeting hepatocytes that
      express high levels of IL-22R1 and IL-10R2. Recently, we have identified high
      expression levels of IL-22R1 and IL-10R2 in liver progenitor cells and hepatic
      stellate cells (HSCs). Overexpression of IL-22 in vivo or treatment with IL-22 in
      vitro promotes proliferation of liver progenitor cells via a signal transducer
      and activator of transcription 3 (STAT3)-dependent mechanism. IL-22 treatment
      also prevents HSC apoptosis in vitro and in vivo. Surprisingly, overexpression of
      IL-22, via either gene targeting or exogenous administration of adenovirus
      expressing IL-22, reduces liver fibrosis and accelerates the resolution of liver
      fibrosis during recovery. The anti-fibrotic effects of IL-22 are mediated via the
      activation of STAT3 in HSCs and subsequent induction of suppressor of cytokine
      signaling 3, which induces HSC senescence. Taken together, the hepatoprotective,
      mitogenic, and anti-fibrotic effects of IL-22 are beneficial in ameliorating
      alcoholic liver injury. Importantly, due to the restricted expression of IL-22R1,
      IL-22 therapy is expected to have few side effects, thus making IL-22 a potential
      candidate for treatment of alcoholic liver disease. 

PMID- 23855299
TI  - Non-alcoholic steatohepatitis: pathogenesis and novel therapeutic approaches.
AB  - Non-alcoholic fatty liver disease (NAFLD) refers to a disease spectrum, ranging
      from mere hepatic steatosis to hepatic necroinflammation (NASH, non-alcoholic
      steatohepatitis). NASH often leads to fibrosis, which can progress to cirrhosis
      with a high risk of liver failure and hepatocellular carcinoma. The course of
      NAFLD is highly variable, and only a minority of patients (2-3%) progress to end
      stage liver disease. However, due to a dramatic increase of the risk factors for
      NAFLD, that is obesity and insulin resistance/type 2 diabetes, that affect 15-30%
      and 7-15% of subjects, in most industrialized countries, respectively, NAFLD has
      become the most frequent liver disease and is even considered a pace setter of
      the metabolic syndrome. Sedentary lifestyle, modern Western nutrition, and
      genetic predispositions have been identified as major causes of NAFLD. These lead
      to liver injury via insulin resistance and an excess of free fatty acids in
      hepatocytes, resulting in oxidant stress and lipotoxicity that promote the
      activation of intracellular stress kinases and apoptosis or necroapoptosis
      (NASH). The damaged hepatocytes directly trigger inflammation and fibrogenesis,
      but can also lead to the emergence of fibrogenic progenitor cells. Moreover, NASH
      is linked to inflammation in peripheral adipose tissues that involves mainly
      macrophages and humoral factors, such as adipokines and cytokines. The most
      efficient treatment is by weight loss and exercise, but (adjunctive)
      pharmacological strategies are urgently needed. Here, we highlight the aspects of
      NAFLD epidemiology and pathophysiology that are beginning to lead to novel
      pharmacological approaches to address this growing health-care challenge.

PMID- 23855298
TI  - Sterile inflammation in the liver and pancreas.
AB  - The ability of tissue injury to result in inflammation is a well-recognized
      phenomenon and is central to a number of common liver and pancreatic diseases
      including alcoholic steatohepatitis and pancreatitis, as well as drug-induced
      liver injury, non-alcoholic steatohepatitis, and pancreatitis from other causes.
      The requirements of extracellular damage-associated molecules and a cytosolic
      machinery labeled the inflammasome have been established in in vitro culture
      systems and in vivo disease models. This has provided a generic insight into the
      pathways involved, and the challenge now is to understand the specifics of these
      mechanisms in relation to the particular insults and organs involved. One reason
      for the excitement in this field is that a number of therapeutic candidates such
      a toll-like receptor antagonists and interleukin-1R antagonists are either
      approved or in clinical trials for other indications. 

PMID- 23855301
TI  - Pilot study of umbilical cord-derived mesenchymal stem cell transfusion in
      patients with primary biliary cirrhosis.
AB  - BACKGROUND AND AIM: Ursodeoxycholic acid (UDCA) treatment is an effective medical
      therapy for patients with primary biliary cirrhosis (PBC); however, 40% of PBC
      patients show an incomplete response to the UDCA therapy. This study aimed to
      investigate the safety and efficacy of umbilical cord-derived mesenchymal stem
      cell (UC-MSC) transfusion in PBC patients with an incomplete response to UDCA.
      METHODS: We conducted a single-arm trial that included seven PBC patients with a
      suboptimal response to UDCA treatment. UC-MSCs were first cultured, and then 0.5
      * 10(6) cells/kg body weights were infused through a peripheral vein. UC-MSCs
      were given three times at 4-week intervals, and patients were followed up for 48
      weeks. Primary outcomes were to evaluate the safety and feasibility of UC-MSC
      treatment, and secondary outcomes were to evaluate liver functions and patient's
      quality of life. RESULTS: No obvious side-effects were found in the patients
      treated with UC-MSCs. Symptoms such as fatigue and pruritus were obviously
      alleviated in most patients after UC-MSC treatment. There was a significant
      decrease in serum alkaline phosphatase and gamma-glutamyltransferase levels at
      the end of the follow-up period as compared with baseline. No significant changes
      were observed in serum alanine aminotransferase, aspartate aminotransferase,
      total bilirubin, albumin, prothrombin time activity, international normalized
      ratio, or immunoglobulin M levels. The Mayo risk score, a prognostic index, was
      also stable during the treatment and follow-up period. CONCLUSIONS: UC-MSC
      transfusion is feasible and well tolerated in patients with PBC who respond only
      partially to UDCA treatment, thus representing a novel therapeutic approach for
      patients in this subgroup. A larger, randomized controlled cohort study is
      warranted to confirm the clinical efficacy of UC-MSC transfusion.

PMID- 23855300
TI  - Alcoholic liver disease: pathogenesis, management, and novel targets for therapy.
AB  - Alcohol use is a leading cause of preventable morbidity and mortality worldwide,
      with much of its negative impact as the result of alcoholic liver disease (ALD).
      ALD is a broad term that encompasses a spectrum of phenotypes ranging from simple
      steatosis to steatohepatitis, progressive fibrosis, cirrhosis, and hepatocellular
      carcinoma. The mechanisms underlying the development of these different disease
      stages are incompletely understood. Standard treatment of ALD, which includes
      abstinence, nutritional support, and corticosteroids, has not changed in the last
      40 years despite continued poor outcomes. Novel therapies are therefore urgently
      needed. The development of such therapies has been hindered by inadequate
      resources for research and unsuitable animal models. However, recent developments
      in translational research have allowed for identification of new potential
      targets for therapy. These targets include: (i) CXC chemokines, (ii) IL-22/STAT3,
      (iii) TNF receptor superfamily, (iv) osteopontin, (v) gut microbiota and
      lipopolysaccharide (LPS), (vi) endocannabinoids, and (vii) inflammasomes. We
      review the natural history, risk factors, pathogenesis, and current treatments
      for ALD. We further discuss the findings of recent translational studies and
      potential therapeutic targets. 

PMID- 23855303
TI  - Interaction of hepatic stellate cells with diverse types of immune cells: foe or
      friend?
AB  - Activated hepatic stellate cells (HSCs) have been considered as a major type of
      cells in liver fibrosis by producing a huge amount of extracellular matrix,
      especially collagen fibers, and profibrotic mediators such as transforming growth
      factor-beta, interleukin-6 and monocyte chemoattractant protein-1. Recently,
      accumulated evidence suggests that the liver is an immunologic organ because of
      enrichment of diverse types of immune cells and that their interactions with HSCs
      are closely related with the progression of liver fibrosis. However, the
      underlying mechanisms of interaction between HSCs and immune cells remain largely
      unknown. Recently, several studies have demonstrated that natural killer cells,
      M2 macrophages, regulatory T cells, and bone marrow derived CD11b(+) Gr1(+)
      immature cells ameliorate liver fibrosis, whereas neutrophils, M1 macrophages,
      CD8 T cells, natural killer T cells and interleukin-17-producing cells accelerate
      liver fibrosis. However, there are still controversial issues about their
      functions during liver fibrogenesis. In this review, we summarize the diversity
      roles of immune cells (e.g. profibrotic/antifibrotic or both) in regulating the
      activation of HSCs during hepatic fibrogenesis, in which several producible
      mediators by HSCs play important roles in the interaction with them. Moreover,
      the current cell-based therapies using immune cells against liver fibrosis are
      discussed.

PMID- 23855302
TI  - Differences in innate immune signaling between alcoholic and non-alcoholic
      steatohepatitis.
AB  - The similar histopathological characteristics of alcoholic steatohepatitis (ASH)
      and non-alcoholic steatohepatitis (NASH), and the crucial role of the innate
      immune response in both conditions may lead to the assumption that ASH and NASH
      represent the same pathophysiological entities caused by different risk factors.
      In this review paper, we elaborate on the pathophysiological differences between
      these two entities and highlight the disease-specific involvement of signaling
      molecules downstream of the Toll-like receptor 4, and the differential mechanism
      by which the inflammasome contributes to ASH versus NASH. Our findings emphasize
      that ASH and NASH have disease-specific mechanisms and therefore represent
      distinct biological entities. Further studies are needed to dissect the emerging
      differences in pathogenesis of these two conditions. 

PMID- 23855304
TI  - Family with sequence similarity 3 gene family and nonalcoholic fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) comprises a disease spectrum ranging
      from simple steatosis (fatty liver) and nonalcoholic steatohepatitis to fibrosis
      and cirrhosis. NAFLD has become the leading cause of chronic liver diseases as
      well as liver-related morbidity and mortality worldwide. NAFLD is also associated
      with increased risk of cardiovascular diseases, hyperlipidemia, and type 2
      diabetes. Insulin resistance in adipose tissues and the liver plays crucial roles
      in the progression of NAFLD. The family with sequence similarity 3 (FAM3) gene
      family is a cytokine-like gene family with four members designated FAM3A, FAM3B,
      FAM3C, and FAM3D, respectively. Increasing evidence suggests that the FAM3 gene
      family members are involved in the pathogenesis of NAFLD. In particular, FAM3B,
      also called pancreatic-derived factor, is an important regulator of glucose and
      lipid metabolism. In obesity status, increased expression and secretion of FAM3B
      in pancreatic islets and liver may induce lipid accumulation in the liver via the
      induction of hepatic insulin resistance and lipogenesis. FAM3A and FAM3D may also
      participate in the regulation of lipid and energy metabolism. In this brief
      review, we discussed the latest findings regarding the role of FAM3 gene family
      members, in particular FAM3B, in the pathogenesis of NAFLD.

PMID- 23855305
TI  - Hepatic stellate cells, liver innate immunity, and hepatitis C virus.
AB  - Chronic hepatitis C virus (HCV) infection can cause liver damage, ranging from
      mild to more severe conditions, such as fibrosis and cirrhosis. Hepatic stellate
      cell (HSC) activation is a key event in HCV-induced liver fibrosis. HSCs express
      several HCV coreceptors that interact with HCV proteins, promoting liver
      fibrogenesis. In addition, HSCs have the ability to engulf apoptotic bodies of
      hepatocytes induced by HCV and trigger a profibrogenic response. Recent studies
      have suggested that HSCs may play a novel role in the liver innate immunity. HSCs
      enhanced differentiation and accumulation of regulatory T cells. HSCs-activated
      natural killer cells could produce gamma-interferon that inhibits HCV
      replication. Importantly, HSCs possess functional Toll-like receptor-3 and
      retinoic acid-inducible gene I that can be activated by their ligands (poly I :C,
      5'ppp-dsRNA), leading to the induction of interferon and inhibition of HCV
      replication in hepatocytes. These new observations highlight the importance of
      HSCs in liver immunity against HCV, which is the focus of this review paper.

PMID- 23855306
TI  - Immunocompetent nontransgenic mouse models for studying hepatitis B virus immune
      responses.
AB  - Although the chronicity of hepatitis B virus (HBV) infection is the result of
      impaired HBV-specific immune responses that cannot eliminate or clear the
      infected hepatocytes efficiently, many issues remained unsettled. It is thus
      crucial to have a suitable laboratory animal to study the immunopathogenesis of
      HBV infection and the mechanisms of HBV persistence. To meet the requirement of a
      mouse model resembling natural chronic HBV infection in human, there are several
      approaches in the development of mouse animal model by using hydrodynamic-based
      transfection of HBV DNA, delivery of adenovirus or adeno-associated viral vectors
      containing HBV DNA for studying HBV immune responses. These immunocompetent
      nontransgenic mouse animal models will provide new approaches to investigate the
      mechanisms of immune pathogenesis in HBV infection. 

PMID- 23855307
TI  - Liver immune-pathogenesis and therapy of human liver tropic virus infection in
      humanized mouse models.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect and replicate
      primarily in human hepatocytes. Few reliable and easy accessible animal models
      are available for studying the immune system's contribution to the liver disease
      progression during hepatitis virus infection. Humanized mouse models
      reconstituted with human hematopoietic stem cells (HSCs) have been developed to
      study human immunology, human immunodeficiency virus 1 infection, and
      immunopathogenesis. However, a humanized mouse model engrafted with both human
      immune and human liver cells is needed to study infection and immunopathogenesis
      of HBV/HCV infection in vivo. We have recently developed the humanized mouse
      model with both human immune and human liver cells (AFC8-hu HSC/Hep) to study
      immunopathogenesis and therapy of HCV infection in vivo. In this review, we
      summarize the current models of HBV/HCV infection and their limitations in
      immunopathogenesis. We will then present our recent findings of HCV infection and
      immunopathogenesis in the AFC8-hu HSC/Hep mouse, which supports HCV infection,
      human T-cell response and associated liver pathogenesis. Inoculation of humanized
      mice with primary HCV isolates resulted in long-term HCV infection. HCV infection
      induced elevated infiltration of human immune cells in the livers of HCV-infected
      humanized mice. HCV infection also induced HCV-specific T-cell immune response in
      lymphoid tissues of humanized mice. Additionally, HCV infection induced liver
      fibrosis in humanized mice. Anti-human alpha smooth muscle actin (alphaSMA)
      staining showed elevated human hepatic stellate cell activation in HCV-infected
      humanized mice. We discuss the limitation and future improvements of the AFC8-hu
      HSC/Hep mouse model and its application in evaluating novel therapeutics, as well
      as studying both HCV and HBV infection, human immune responses, and associated
      human liver fibrosis and cancer. 

PMID- 23855309
TI  - Reversal of hepatitis B virus-induced systemic immune tolerance by intrinsic
      innate immune stimulation.
AB  - Systemic immune tolerance induced by chronic hepatitis B virus (HBV) infection is
      a significant question, but the mechanism of which remains unclear. In this mini
      review, we summarize the impaired innate and adaptive immune responses involved
      in immune tolerance in chronic HBV infection. Furthermore, we delineate a novel
      dual functional small RNA to inhibit HBV replication and stimulate innate
      immunity against HBV, which proposed a promising immunotherapeutic intervention
      to interrupt HBV-induced immunotolerance. A mouse model of HBV persistence was
      established and used to observe the immune tolerant to HBV vaccination, the cell
      intrinsic immune tolerance of which might be reversed by chemically synthesized
      dual functional small RNA (3p-hepatitis B Virus X gene [HBx]-small interfering
      RNA) in vitro experiments and by biologically constructed dual functional vector
      (single-stranded RNA-HBx- short hairpin RNA) in vivo experiment using HBV-carrier
      mice. 

PMID- 23855308
TI  - Forkhead box class O transcription factors in liver function and disease.
AB  - The forkhead box transcription factor class O (FOXO) family represents a group of
      transcription factors that is required for a number of stress-related
      transcriptional programs including antioxidant response, gluconeogenesis, cell
      cycle control, apoptosis, and autophagy. The liver utilizes several FOXO
      dependent pathways to adapt to its routine cycles of feeding and fasting and to
      respond to the stresses induced by disease. FOXO1 is a direct transcriptional
      regulator of gluconeogenesis, reciprocally regulated by insulin, and has profound
      effects on hepatic lipid metabolism. FOXO3 is required for antioxidant responses
      and autophagy and is altered in hepatitis C infection and fatty liver. Emerging
      evidence suggests dysregulation of FOXO3 in some hepatocellular carcinomas. FOXOs
      are notable for the extensive number of functionally significant
      posttranslational modifications that they undergo. Recent advances in our
      understanding how FOXOs are regulated are providing a more detailed picture of
      how specific combinations of posttranslational modifications alter both nuclear
      translocation as well as transcriptional specificity under different conditions.
      This review summarizes emerging knowledge of FOXO function in the liver, FOXO
      changes in liver disease, and the posttranslational modifications responsible for
      these effects.

PMID- 23855310
TI  - Photoactive, porous honeycomb films prepared from Rose Bengal-grafted
      polystyrene.
AB  - Honeycomb-structured porous polymer films based on photosensitizer-grafted
      polystyrene are prepared through the breath figure process. Rose Bengal (RB)
      photosensitizer is first attached to a well-defined poly(styrene-stat-4
      vinylbenzyl chloride) statistical copolymer, synthesized by nitroxide-mediated
      radical polymerization. The RB grafted poly(styrene-stat-4-vinylbenzyl chloride)
      (ca. 20,000 g mol(-1) molar mass, 1.2 dispersity) leads to porous polymer films,
      with a hexagonal pore pattern, while a simple mixture of poly(styrene-stat-4
      vinylbenzyl chloride) and the insoluble RB photosensitizer produced unstructured,
      nonporous films. The RB-grafted honeycomb films, compared with the corresponding
      nonporous flat films, are more efficient for oxidation of organic molecules via
      singlet oxygen production at a liquid/solid interface. The oxidations of 1,5
      dihydroxynaphthalene to juglone and alpha-terpinene to ascaridole are followed in
      ethanol in the presence of both types of films. Oxidation of the organic
      molecules is a factor 5 greater with honeycomb compared to the nonporous films.
      This gain is ascribed to two factors: the specific location of the polar
      photosensitizer at the film interface and the greater exchange surface, as
      revealed by fluorescence and scanning electron microscopies.

PMID- 23855311
TI  - Theoretical study of differential enthalpy of absorption of CO2 with MEA and MDEA
      as a function of temperature.
AB  - Temperature dependent correlations for enthalpy of deprotonation, carbamate
      formation, and heat of absorption of the overall reaction between aqueous MEA and
      MDEA and gaseous CO2 are calculated on the basis of computational chemistry based
      ln K values input to the Gibbs-Helmholtz equation. Temperature dependency of
      reaction equilibrium constants for deprotonation and carbamate formation
      reactions is calculated with the SM8T continuum solvation model coupled with
      density functional theoretical calculations at the B3LYP/6-311++G(d,p) level of
      theory. Calculated reaction equilibrium constants and enthalpies of individual
      reactions and overall heat of absorption are compared against experimental data
      in the temperature range 273.15-373 K. Temperature dependent correlations for
      different reaction equilibrium constants and enthalpies of reactions are given.
      These correlated results can be used in thermodynamic models such as UNIQUAC and
      NRTL for better understanding of post-combustion CO2 capture solvent chemistry. 

PMID- 23855313
TI  - Drug reaction with eosinophilia and systemic symptoms (DRESS): an original
      multisystem adverse drug reaction. Results from the prospective RegiSCAR study.
AB  - BACKGROUND: Cases of severe drug hypersensitivity, demonstrating a variable
      spectrum of cutaneous and systemic involvement, are reported under various names,
      especially drug reaction with eosinophilia and systemic symptoms (DRESS). Case
      definition and overlap with other severe cutaneous adverse reactions (SCAR) are
      debated. OBJECTIVES: To analyse the spectrum of signs and symptoms of DRESS and
      distribution of causative drugs in a large multicentre series. PATIENTS AND
      METHODS: RegiSCAR, a multinational registry of SCAR, prospectively enrolled 201
      potential cases from 2003 to mid-2009. Using a standardized scoring system, 117
      cases were validated as showing probable or definite DRESS. RESULTS: The
      male/female ratio was 0.80; females were borderline significantly younger than
      males. Next to the ubiquitous exanthema, the main features were eosinophilia
      (95%), visceral involvement (91%), high fever (90%), atypical lymphocytes (67%),
      mild mucosal involvement (56%) and lymphadenopathy (54%). The reaction was
      protracted in all but two patients; two patients died during the acute phase.
      Drug causality was plausible in 88% of cases. Antiepileptic drugs were involved
      in 35%, allopurinol in 18%, antimicrobial sulfonamides and dapsone in 12% and
      other antibiotics in 11%. The median time interval after drug intake was 22 days
      (interquartile range 17-31) for all drugs with (very) probable causality, with
      differences between drugs. CONCLUSION: This prospective observational study
      supports the hypothesis that DRESS is an original phenotype among SCAR in terms
      of clinical and biological characteristics, causative drugs, and time relation.
      The diversity of causative drugs was rather limited, and mortality was lower than
      that suggested by prior publications.

PMID- 23855314
TI  - Successful outcome in a rare case of pregnancy with familial hypercholesterolemia
      and dilated cardiomyopathy.
AB  - Familial hypercholesterolemia is a rare disorder characterized by high
      cholesterol levels and early cardiovascular disease. Early detection and
      treatment with statins and other hypolipidemic agents are effective in
      heterozygous patients. Low-density lipoprotein apheresis and liver
      transplantation are treatment options in homozygous familial
      hypercholesterolemia. We report a case of a 27-year-old pregnant woman with
      familial hypercholesterolemia who presented with breathlessness and swelling in
      the joints. She had been taking statins previously, which were stopped and she
      had been put on low-lipid and low-residue diet to reduce the risk of acute
      coronary event and sudden intrauterine death. She was found to have dilated
      cardiomyopathy with 25% ejection fraction. At 36 weeks of gestation, we carried
      out cesarean section in view of poor biophysical profile. Familial
      hypercholesterolemia is a very rare disorder with only a few cases reported in
      the published work during pregnancy. Statins are contraindicated during pregnancy
      and diet modification remains the mainstay of therapy.

PMID- 23855315
TI  - Evaluation of knowledge and attitudes among primary care physicians in Cavan
      Monaghan as 'gatekeepers-in-waiting' for the introduction of Carepath for
      Overcoming Psychosis Early (COPE).
AB  - AIM: To investigate general practitioners' current knowledge of and attitudes
      towards psychosis and its management by Cavan-Monaghan Mental Health Service,
      Ireland, prior to their involvement in the introduction of an early intervention
      service. METHODS: As part of a continuing medical education programme for
      psychosis, delivered to all 32 general practitioners practising in this region,
      participants were asked to complete a 29-item questionnaire designed to assess
      their baseline knowledge and attitudes. RESULTS: All 32 general practitioners
      participated in the study. Although 17% had received no previous psychiatric
      training, 93% described their knowledge of psychiatric disorders as average or
      above average. However, only 53% could correctly identify all of a set of
      psychiatric symptoms related to psychosis. Only 50% felt comfortable initiating
      treatment for psychotic symptoms. Whereas only 40% had heard of the early
      intervention model, 89% believed it to be advantageous. Easy accessibility to
      services and rapid assessment of patients referred were most commonly reported as
      helpful. However, concerns were expressed about the potential for associated
      increases in workload. CONCLUSIONS: As 'gatekeepers-in-waiting', these general
      practitioners will have a vital role in effective implementation of the early
      intervention service for psychosis. However, their knowledge needs improvement,
      through regular educational sessions, and this service must be responsive to
      their needs. In addition, general practitioners' concerns regarding the potential
      for increased workload must be adequately addressed in order to maintain
      enthusiasm and collaboration at the interface between primary care and mental
      health services, particularly in the context of early intervention.

PMID- 23855316
TI  - Common sleep disorders: management strategies and pregnancy outcomes.
AB  - Sleep disorders, prevalent in industrialized countries, are associated with
      adverse health outcomes such as hypertension, diabetes, and obesity. Disturbed
      sleep during pregnancy is frequently overlooked by health care providers, yet
      recent studies suggest there is an association between sleep disorders and
      adverse pregnancy outcomes, including preeclampsia, elevated serum glucose,
      depression, prolonged labor, and cesarean birth. Growing evidence indicates that
      the recognition and management of prenatal sleep disorders may minimize adverse
      pregnancy outcomes and improve maternal and fetal well-being. This focused review
      of prenatal sleep disturbance literature suggests there are 3 main sleep
      disorders of interest: breathing-related sleep disorders (ie, habitual snoring
      and obstructive sleep apnea), restless legs syndrome, and insomnia. These sleep
      disorders are common in pregnancy and have maternal and fetal consequences if
      left untreated. This article describes sleep disorders of pregnancy, elucidates
      their relationship with maternal and neonatal outcomes, and presents current
      evidence regarding diagnostic and management strategies. 

PMID- 23855317
TI  - Mazzotti reaction with eosinophilia after undergoing oral ivermectin for scabies.

PMID- 23855318
TI  - A pilot study comparing two weight loss maintenance interventions among low
      income, mid-life women.
AB  - BACKGROUND: Despite high obesity prevalence rates, few low-income midlife women
      participate in weight loss maintenance trials. This pilot study aims to assess
      the effectiveness of two weight loss maintenance interventions in this under
      represented population. METHODS: Low-income midlife women who completed a 16-week
      weight loss intervention and lost  >= 8 lbs (3.6 kg) were eligible to enroll in
      one of two 12-month maintenance programs. The programs were similar in content
      and had the same number of total contacts, but were different in the contact
      modality (Phone + Face-to-Face vs. Face-to-Face Only). Two criteria were used to
      assess successful weight loss maintenance at 12 months: (1) retaining a loss of 
      >= 5% of body weight from the start of the weight loss phase and (2) a change in
      body weight of  < 3%, from the start to the end of the maintenance program.
      Outcome measures of changes in physiologic and psychosocial factors, and
      evaluations of process measures and program acceptability (measured at 12 months)
      are also reported. For categorical variables, likelihood ratio or Fisher's Exact
      (for small samples) tests were used to evaluate statistically significant
      relationships; for continuous variables, t-tests or their equivalents were used
      to assess differences between means and also to identify correlates of weight
      loss maintenance. RESULTS: Overall, during the 12-month maintenance period, 41%
      (24/58) of participants maintained a loss of  >= 5% of initial weight and 43%
      (25/58) had a <3% change in weight. None of the comparisons between the two
      maintenance programs were statistically significant. However, improvements in
      blood pressure and dietary behaviors remained significant at the end of the 12
      month maintenance period for participants in both programs. Participant
      attendance and acceptability were high for both programs. CONCLUSIONS: The
      effectiveness of two pilot 12-month maintenance interventions provides support
      for further research in weight loss maintenance among high-risk, low-income
      women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00288301.

PMID- 23855319
TI  - Fluorescent PCR-based gene dose analysis for detection of deletion mutations in
      carriers of haemophilia.

PMID- 23855320
TI  - Genome-wide analysis of short interspersed nuclear elements SINES revealed high
      sequence conservation, gene association and retrotranspositional activity in
      wheat.
AB  - Short interspersed nuclear elements (SINEs) are non-autonomous non-LTR
      retroelements that are present in most eukaryotic species. While SINEs have been
      intensively investigated in humans and other animal systems, they are poorly
      studied in plants, especially in wheat (Triticum aestivum). We used quantitative
      PCR of various wheat species to determine the copy number of a wheat SINE family,
      termed Au SINE, combined with computer-assisted analyses of the publicly
      available 454 pyrosequencing database of T. aestivum. In addition, we utilized
      site-specific PCR on 57 Au SINE insertions, transposon methylation display and
      transposon display on newly formed wheat polyploids to assess
      retrotranspositional activity, epigenetic status and genetic rearrangements in Au
      SINE, respectively. We retrieved 3706 different insertions of Au SINE from the
      454 pyrosequencing database of T. aestivum, and found that most of the elements
      are inserted in A/T-rich regions, while approximately 38% of the insertions are
      associated with transcribed regions, including known wheat genes. We observed
      typical retrotransposition of Au SINE in the second generation of a newly formed
      wheat allohexaploid, and massive hypermethylation in CCGG sites surrounding Au
      SINE in the third generation. Finally, we observed huge differences in the copy
      numbers in diploid Triticum and Aegilops species, and a significant increase in
      the copy numbers in natural wheat polyploids, but no significant increase in the
      copy number of Au SINE in the first four generations for two of three newly
      formed allopolyploid species used in this study. Our data indicate that SINEs may
      play a prominent role in the genomic evolution of wheat through stress-induced
      activation.

PMID- 23855322
TI  - Further development and construct validation of MMPI-2-RF indices of global
      psychopathy, fearless-dominance, and impulsive-antisociality in a sample of
      incarcerated women.
AB  - Replicating and extending research by Sellbom et al. (M. Sellbom, Y. S. Ben
      Porath, C. J. Patrick, D. B. Wygant, D. M. Gartland, & K. P. Stafford, 2012,
      Development and Construct Validation of the MMPI-2-RF Measures of Global
      Psychopathy, Fearless-Dominance, and Impulsive-Antisociality, Personality
      Disorders: Theory, Research, and Treatment, 3, 17-38), the current study examined
      the criterion-related validity of three self-report indices of psychopathy that
      were derived from scores on the Minnesota Multiphasic Personality Inventory
      (MMPI)-2-Restructured Form (MMPI-2-RF; Y. S. Ben-Porath & A. Tellegen, 2008,
      Minnesota Multiphasic Personality Inventory-2-Restructured Form: Manual for
      Administration, Scoring, and Interpretation, Minneapolis, MN: University of
      Minnesota Press). We estimated psychopathy indices by regressing scores from the
      Psychopathic Personality Inventory (PPI; S. O. Lilienfeld & B. P. Andrews, 1996,
      Development and Preliminary Validation of a Self-Report Measure of Psychopathic
      Personality Traits in Noncriminal Populations, Journal of Personality Assessment,
      66, 488-524) and its two distinct facets, Fearless-Dominance and Impulsive
      Antisociality, onto conceptually selected MMPI-2-RF scales. Data for a newly
      collected sample of 230 incarcerated women were combined with existing data from
      Sellbom et al.'s (2012) male correctional and mixed-gender college samples to
      establish regression equations with optimal generalizability. Correlation and
      regression analyses were then used to examine associations between the MMPI-2-RF
      based estimates of PPI psychopathy and criterion measures (i.e., other well
      established measures of psychopathy and conceptually related personality traits),
      and to evaluate whether gender moderated these associations. The MMPI-2-RF-based
      psychopathy indices correlated as expected with criterion measures and showed
      only one significant moderating effect for gender, namely, in the association
      between psychopathy and narcissism. These results provide further support for the
      validity of the MMPI-2-RF-based estimates of PPI psychopathy, and encourage their
      use in research and clinical contexts.

PMID- 23855321
TI  - The presentation of metabolic dysfunction and the relationship with energy output
      in breast cancer survivors: a cross-sectional study.
AB  - BACKGROUND: Breast cancer prognosis can be adversely influenced by obesity,
      physical inactivity and metabolic dysfunction. Interventions aimed at improving
      surrogate markers of breast cancer risk such as insulin resistance may result in
      improved breast cancer outcomes. The design of such interventions may be improved
      through increased understanding of metabolic presentation in this cohort. This
      cross-sectional study aimed to characterise the metabolic profile of breast
      cancer survivors relative to abdominal obesity and insulin resistance. A
      secondary aim was to compare measures of energy output across these groups.
      METHODS: Sixty-nine women (mean (SD) age 53.43 (9.39) years) who had completed
      adjuvant chemotherapy and radiotherapy for breast cancer were recruited. All
      measures were completed during one assessment conducted 3.1 (1.0) years post
      diagnosis. Body composition was measured by bioimpedance analysis and waist
      circumference (WC). Fasting (12 hour) blood samples were drawn to measure lipid
      profile, glucose, insulin, glycosylated haemoglobin A1c (HBA1c) and C-reactive
      protein (CRP). Insulin resistance was estimated by the homeostatic model
      assessment index (HOMA-IR)). Energy output was evaluated by resting metabolic
      rate (RMR) measured by indirect calorimetry and physical activity measured by
      accelerometry. Characteristics were compared across four groups (1. WC <80 cm,
      not insulin resistant; 2. WC 80-87.9 cm, not insulin resistant; 3. WC >88 cm, not
      insulin resistant; 4. WC >80 cm, insulin resistant) using ANOVA (p < 0.05).
      RESULTS: Group 4 was characterised by significant disturbances in measures of
      glucose metabolism (glucose, insulin, HOMA-IR and HBA1c) and raised CRP compared
      to other groups. Group 4 also displayed evidence of dyslipidemia and higher body
      composition values compared to Groups 1 and 2. Both absolute and adjusted RMR
      were significantly higher in the Group 4 versus all other groups. Physical
      activity levels were similar for all groups. CONCLUSIONS: The results from this
      study suggest that participants who were both centrally obese and insulin
      resistant showed evidence of dyslipidemia, low-grade inflammation and glucose
      dysregulation. Metabolic profiles of participants who were centrally obese only
      were not significantly different from lean participants. Consideration of
      baseline metabolic presentation may be useful when considering the therapeutic
      targets for future interventions in this cohort.

PMID- 23855323
TI  - Mock jurors' use of error rates in DNA database trawls.
AB  - Forensic science is not infallible, as data collected by the Innocence Project
      have revealed. The rate at which errors occur in forensic DNA testing-the so
      called "gold standard" of forensic science-is not currently known. This article
      presents a Bayesian analysis to demonstrate the profound impact that error rates
      have on the probative value of a DNA match. Empirical evidence on whether jurors
      are sensitive to this effect is equivocal: Studies have typically found they are
      not, while a recent, methodologically rigorous study found that they can be. This
      article presents the results of an experiment that examined this issue within the
      context of a database trawl case in which one DNA profile was tested against a
      multitude of profiles. The description of the database was manipulated (i.e.,
      "medical" or "offender" database, or not specified) as was the rate of error
      (i.e., one-in-10 or one-in-1,000). Jury-eligible participants were nearly twice
      as likely to convict in the offender database condition compared to the condition
      not specified. The error rates did not affect verdicts. Both factors, however,
      affected the perception of the defendant's guilt, in the expected direction,
      although the size of the effect was meager compared to Bayesian prescriptions.
      The results suggest that the disclosure of an offender database to jurors might
      constitute prejudicial evidence, and calls for proficiency testing in forensic
      science as well as training of jurors are echoed.

PMID- 23855324
TI  - Recent victimization increases risk for violence in justice-involved persons with
      mental illness.
AB  - A large body of research has examined relationships between distal experiences of
      victimization and the likelihood of engaging in violence later in life. Less is
      known about the influence of recent violent victimization on risk for violence
      perpetration. To our knowledge, this is the first study to examine prospectively
      whether recent victimization in adulthood increases the risk of future violence.
      Specifically, the present study assessed the incremental validity of recent
      violent victimization in the prediction of future violence in a sample of justice
      involved adults with serious mental illness. The study examined (a) whether
      recent experiences of violent victimization (i.e., within 6 months of the
      baseline assessment) predicted a greater likelihood of perpetrating violence in
      the next year, and (b) whether inclusion of recent victimization enhanced the
      predictive validity of a model of violence risk in a sample of justice-involved
      adults with severe mental illness (N = 167). Hierarchical logistic regression
      analyses indicated that exposure to recent violent victimization at the baseline
      assessment predicted a greater likelihood of engaging in violent behavior during
      the year follow-up period. Additionally, recent exposure to violence at the
      baseline assessment continued to explain a significant amount of variance in a
      model of future violence perpetration above the variance accounted for by well
      established violence risk factors. Taken together, the findings suggest that
      recent victimization is important to consider in understanding and evaluating
      risk of violence by persons with mental disorders who are involved in the
      criminal justice system.

PMID- 23855325
TI  - Appearance-change instruction effects on eyewitness lineup identification
      accuracy are not moderated by amount of appearance change.
AB  - Instructing witnesses that a criminal may have changed appearance prior to
      showing them a lineup has been shown to increase false identifications without
      increasing correct identifications (S. D. Charman & G. L. Wells, 2007, Is the
      appearance-change instruction a good idea? Law and Human Behavior, Vol. 31, pp. 3
      22). However, the generalizability of the effects of this appearance-change
      instruction (ACI) is unknown, and there are reasons to believe that the
      instruction's effects may be moderated by the amount of appearance change the
      criminal has actually undergone. The current study tested this hypothesis.
      Undergraduate students (N = 315) were exposed to a series of target faces and
      lineups, some of which contained the target and some of which did not, and made
      identification decisions. Half of the participants received a standard ACI prior
      to each lineup; the other half did not. The targets varied with respect to the
      amount to which their appearance had changed. Results indicated that the ACI
      inflated false identifications without inflating correct identifications, and
      that these effects did not depend on the amount of appearance change the target
      had undergone. Current recommendations to administer the ACI seem to be unfounded
      and may be harmful to the reliability of identification evidence.

PMID- 23855326
TI  - The club concept: targeting behavioral issues in a residential setting for
      cognitively impaired adults.
AB  - Behavior and psychological symptoms of dementia are common in residential care
      facilities. These symptoms not only detract from the quality of life of the
      resident with dementia, but they can be disruptive to the unit and result in harm
      to staff and other residents. With the trend away from pharmacological
      management, other creative psychosocial-environmental strategies are being
      explored. One innovative approach involves the use of the club concept, where
      selected agitated residents spend a portion of the day in a separate structured
      environment. This program combines trained staff and tailored activities that
      optimize mental stimulation, functional independence, and self-esteem. Benefits
      include reduced incidents of aggressive behaviors and use of psychoactive
      medications, as well as enhanced quality of life. Not only do the participants
      benefit from time spent in this specialized setting, but the therapeutic milieu
      of the facility is also enhanced. Further evaluation of such strategies is needed
      to quantify the benefits of targeted behavioral interventions for those with
      cognitive impairment.

PMID- 23855327
TI  - Examining the lived experience of nursing home quality improvement: the case of a
      multifacility falls reduction project.
AB  - We conducted a case study based on interviews with nursing home employees (staff
      and management) participating in a falls reduction project to better understand
      the lived experience of nursing home quality improvement. Our case study was part
      of an evaluation of an innovative pay-for-performance policy in the state of
      Minnesota. In-depth semi-structured interviews were conducted with 37 nursing
      home employees from within each of the 13 facilities participating in the
      successful falls reduction project. Our analysis focused on respondent
      perceptions of the quality improvement implementation process. Interview
      respondents noted the importance of organizational flexibility and adaptation to
      change; communication and connections between residents, family members, and
      staff; and the importance of input from diverse roles. Importantly, interview
      respondents noted changes that extended well beyond the domain of falls.
      Knowledge from this study highlights the experiences of care providers enacting
      change and potentially informs the development of management and program policies
      that encourage and reward quality nursing home care.

PMID- 23855328
TI  - Cardiovascular effects and enjoyment of exercise gaming in older adults.
AB  - The purpose of this study was to quantify the cardiovascular responses and
      enjoyment of one trial of electronic exercise gaming (EG) (Nintendo((r)) Wii(TM)
      Tennis) in healthy, older adults (mean age = 81 [SD = 4 years]). Findings
      indicate that 15 minutes of EG moderately increased heart rate (p < 0.001), blood
      pressure (p < 0.001), and perceived exertion (p < 0.0001) compared to resting
      levels. This corresponded to achieving 64% of age-predicted maximum heart rate.
      No differences were observed for the cardiovascular responses to EG between
      genders, but participants taking beta-blocker drugs showed an attenuated response
      (p < 0.05). All participants completed EG tennis without excessive fatigue, with
      86% of participants enjoying the experience. There were only a few cases of EG
      related arrhythmias (n = 2) and post-exercise muscle soreness (n = 3). These
      results suggest that Nintendo Wii Tennis EG technology represents an enjoyable,
      moderate intensity physical activity for healthy, older adults.

PMID- 23855329
TI  - Rates of computational errors for scoring the SIRS primary scales.
AB  - We entered item scores for the Structured Interview of Reported Symptoms (SIRS;
      Rogers, Bagby, & Dickens, 1991) into a spreadsheet and compared computed scores
      with those hand-tallied by examiners. We found that about 35% of the tests had at
      least 1 scoring error. Of SIRS scale scores tallied by examiners, about 8% were
      incorrectly summed. When the errors were corrected, only 1 SIRS classification
      was reclassified in the fourfold scheme used by the SIRS. We note that mistallied
      scores on psychological tests are common, and we review some strategies for
      reducing scale score errors on the SIRS.

PMID- 23855330
TI  - Two-step impact of Amphotericin B (AmB) on lipid membranes: ESR experiment and
      computer simulations.
AB  - In this study, the electron spin resonance (ESR) method was used to examine the
      effect of Amphotericin B (AmB) molecules on the fluidity of model membranes made
      of dipalmitoylphosphatidylcholine (DPPC). The changes occurring under increased
      AmB concentrations in the spectroscopic parameters of spin probes placed in
      liposomes were determined. Three probes were used, penetrating the membrane at
      different depths which allowed the changes in its fluidity to be found in the
      transverse section. A computer model of the surface layer of membrane, with AmB
      admixture, was developed and subjected to computer simulation. The effect of
      changing concentration of the admixture on the binding energy in the system of
      dipoles representing the surface of the membrane was examined. The ESR studies
      showed that the process of accumulation of AmB molecules in the membrane has two
      stages, marked by local maxima in the ESR spectra. The first appears for
      concentrations of ca. 0.25-0.5% and the second appears for ca. 2.5-3% AmB of its
      molar ratio to DPPC. The computer simulations permitted reconstructing the two
      stage mechanism of interaction between the molecules and the membrane. They
      demonstrated that, at low concentrations, the AmB molecules position themselves
      flat on the membrane surface. After the threshold concentration is exceeded, they
      re-orientate to a vertical position. This process leads to the perforation of the
      membrane.

PMID- 23855331
TI  - Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon
      tetrachloride-induced chronic injury in rats.
AB  - CONTEXT: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve
      liver ischemia-reperfusion-induced injury in rats. OBJECTIVE: This study was
      designed to determine whether the recombinant BPTI (rBPTI) can prevent the
      chronic liver injury induced by CCl4 in rats. MATERIALS AND METHODS: Fifty male
      Wistar rats were divided into five groups. Rats were treated with 40% CCl4 at a
      dose of 2 ml/kg body weight twice a week subcutaneously for 12 weeks. In the 8th
      week, they were administered intraperitoneally with rBPTI (80 MU/kg), BPTI (80
      MU/kg) or hepatocyte growth-promoting factor (pHGF; 100 mg/kg) daily for the next
      4 weeks. RESULTS: rBPTI significantly prevented the disruption of liver function
      of alanine aminotransferase (ALT; 172.7 +/- 18.16 versus 141.2 +/- 15.28,
      p=0.003), aspartate aminotransferase (AST; 225.10 +/- 36.54 versus 170.06 +/-
      27.14, p=0.007) and hydroxyproline (Hyp; 1.14 +/- 0.27 versus 0.62 +/- 0.17,
      p=0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive
      substances (TBARS; 1.15 +/- 0.16 versus 0.87 +/- 0.15, p=0.003) and increased the
      activities of superoxide dismutase (SOD; 6.07 +/- 0.95 versus 7.75 +/- 1.12,
      p=0.007). rBPTI reduced the production of cytokines of IL-1beta and TGF-beta. The
      hepatocyte necrosis, fibrosis, fatty degeneration and inflammatory cell
      infiltration were ameliorated by rBPTI administration. CONCLUSION: This study
      demonstrated that rBPTI exerted a hepatoprotective effect on chronic liver
      fibrosis induced by CCl4, which suggests that rBPTI may have the potential
      application for chronic liver injury induced by drugs metabolism and toxic
      substances.

PMID- 23855332
TI  - The effect of host star spectral energy distribution and ice-albedo feedback on
      the climate of extrasolar planets.
AB  - Planetary climate can be affected by the interaction of the host star spectral
      energy distribution with the wavelength-dependent reflectivity of ice and snow.
      In this study, we explored this effect with a one-dimensional (1-D), line-by
      line, radiative transfer model to calculate broadband planetary albedos as input
      to a seasonally varying, 1-D energy balance climate model. A three-dimensional (3
      D) general circulation model was also used to explore the atmosphere's response
      to changes in incoming stellar radiation, or instellation, and surface albedo.
      Using this hierarchy of models, we simulated planets covered by ocean, land, and
      water-ice of varying grain size, with incident radiation from stars of different
      spectral types. Terrestrial planets orbiting stars with higher near-UV radiation
      exhibited a stronger ice-albedo feedback. We found that ice extent was much
      greater on a planet orbiting an F-dwarf star than on a planet orbiting a G-dwarf
      star at an equivalent flux distance, and that ice-covered conditions occurred on
      an F-dwarf planet with only a 2% reduction in instellation relative to the
      present instellation on Earth, assuming fixed CO(2) (present atmospheric level on
      Earth). A similar planet orbiting the Sun at an equivalent flux distance required
      an 8% reduction in instellation, while a planet orbiting an M-dwarf star required
      an additional 19% reduction in instellation to become ice-covered, equivalent to
      73% of the modern solar constant. The reduction in instellation must be larger
      for planets orbiting cooler stars due in large part to the stronger absorption of
      longer-wavelength radiation by icy surfaces on these planets in addition to
      stronger absorption by water vapor and CO(2) in their atmospheres, which provides
      increased downwelling longwave radiation. Lowering the IR and visible-band
      surface ice and snow albedos for an M-dwarf planet increased the planet's climate
      stability against changes in instellation and slowed the descent into global ice
      coverage. The surface ice-albedo feedback effect becomes less important at the
      outer edge of the habitable zone, where atmospheric CO(2) could be expected to be
      high such that it maintains clement conditions for surface liquid water. We
      showed that ~3-10 bar of CO(2) will entirely mask the climatic effect of ice and
      snow, leaving the outer limits of the habitable zone unaffected by the spectral
      dependence of water ice and snow albedo. However, less CO(2) is needed to
      maintain open water for a planet orbiting an M-dwarf star than would be the case
      for hotter main-sequence stars.

PMID- 23855334
TI  - Assessing impulsivity in prepubertal male rats: a novel device and method to
      assess motor and cognitive impulsivity.
AB  - The use of animal models in studies of impulsivity has made valuable
      contributions to our understanding of this behavioral trait as it relates to
      disorders such as attention deficit hyperactivity disorder. The objective of this
      work was to develop a paradigm that would make it possible to evaluate both motor
      and cognitive impulsivity using the same device after a short training period.
      The operant behavior demanded in this device consists in having rats cross a
      bridge after receiving a signal to obtain a reward that is available on a goal
      platform in a Wait-to-Go-signal task, or in crossing a bridge after the animals
      make a choice between two alternatives in a Delay-discounting task. To test this
      device and method, a study was conducted using an animal model of dopaminergic
      dysfunction produced by prenatal alcohol treatment (which has been shown to cause
      attention deficits and alterations of impulsivity in adult rats). Compared with
      controls, prepubertal male rats treated prenatally with alcohol showed both
      higher cognitive and higher motor impulsivity as assessed by the parameters used.
      Although attention changes proved not to be dependent on prenatal treatment, they
      were sensitive to the task performed. The device and methods introduced herein
      thus constitute useful instruments for evaluating impulsivity. Their significant
      advantages include a short investment in training time, and the ability to assess
      different types of impulsivity from the vantage point of distinct theoretical
      perspectives.

PMID- 23855335
TI  - Editorial: The effects of anticancer agents on cell apoptosis and on the
      expression of cancer-related genes.

PMID- 23855333
TI  - Randomized, placebo-controlled pilot trial of gabapentin during an outpatient,
      buprenorphine-assisted detoxification procedure.
AB  - This pilot study examined the efficacy of the N-type calcium channel blocker
      gabapentin to improve outcomes during a brief detoxification protocol with
      buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a
      5-week, double-blind, placebo-controlled trial examining the effects of
      gabapentin during a 10-day outpatient detoxification from buprenorphine.
      Participants were inducted onto buprenorphine sublingual tablets during Week 1,
      were randomized and inducted onto gabapentin or placebo during Week 2, underwent
      a 10-day buprenorphine taper during Weeks 3 and 4, and then were tapered off
      gabapentin/placebo during Week 5. Assessments included thrice-weekly opioid
      withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13
      male; 17 Caucasian, 3 African American, 4 Latino; mean age 29.7 years)
      participated in the detoxification portion of the study (gabapentin, n = 11;
      placebo, n = 13). Baseline characteristics did not differ significantly between
      groups. Self-reported and observer-rated opioid withdrawal ratings were
      relatively low and did not differ between groups during the buprenorphine taper.
      Urine results showed a Drug * Time interaction, such that the probability of
      opioid-positive urines significantly decreased over time in the gabapentin versus
      placebo groups during Weeks 3 and 4 (OR = 0.73, p = .004). These results suggest
      that gabapentin reduces opioid use during a 10-day buprenorphine detoxification
      procedure.

PMID- 23855336
TI  - Cordycepin suppresses integrin/FAK signaling and epithelial-mesenchymal
      transition in hepatocellular carcinoma.
AB  - Cordycepin, also known as 3-deoxyadenosine, is an analogue of adenosine extracted
      from the traditional Chinese medicine "Dong Chong Xia Cao". Cordycepin is an
      active small molecular weight compound and is implicated in modulating multiple
      physiological functions including immune activation, anti-aging and anti-tumor
      effects. Several studies have indicated that cordycepin suppresses tumor
      progression. However, the signaling pathways involved in cordycepin regulating
      cancer cell motility, invasiveness and epithelial-mesenchymal transition (EMT)
      remain unclear. In this study, we found that cordycepin inhibits hepatocellular
      carcinoma (HCC) cell proliferation and migration/invasion. Treatment of
      cordycepin results in the increasing expression of epithelial marker, Ecadherin
      while no significant effect was found on N-cadherin alpha-catenin and beta
      catenin. Furthermore, although the expression of focal adhesion kinase (FAK) was
      slightly reduced, the level of phosphorylated FAK was significantly reduced by
      the treatment of cordycepin. In addition, cordycepin significantly suppresses the
      expression of integrin alpha3, integrin alpha6 and integrin beta1 which are
      crucial interacting partners of FAK in regulating the focal adhesion complex.
      These results suggest cordycepin may contribute to EMT, antimigration/ invasion
      and growth inhibitory effects of HCC by suppressing E-cadherin and integrin/FAK
      signaling. Thus, cordycepin is a potential therapeutic or supplementary agent for
      preventing HCC tumor progression. 

PMID- 23855338
TI  - Structure, synthesis, and biological activity of a C-20 bisacetylenic alcohol
      from a marine sponge Callyspongia sp.
AB  - An optically inactive C-20 bisacetylenic alcohol, (4E,16E)-icosa-4,16-diene-1,19
      diyne-3,18-diol, was isolated from a marine sponge Callyspongia sp. as a result
      of screening of antilymphangiogenic agents from marine invertebrates. An optical
      resolution using chiral-phase HPLC gave each enantiomer, (-)-1 and (+)-2. Because
      the natural and synthetic enantiomers 1 and 2 showed different biological
      properties, we investigated the structure-activity relationships of bisacetylenic
      alcohols using 11 synthetic derivatives, and it is clarified that the essential
      structural unit for antiproliferative activity is the "1-yn-3-ol" on both termini
      and that there is a minimum chain length that connects the "1-yn-3-ol" moieties. 

PMID- 23855337
TI  - A tutorial on sensitivity analyses in clinical trials: the what, why, when and
      how.
AB  - BACKGROUND: Sensitivity analyses play a crucial role in assessing the robustness
      of the findings or conclusions based on primary analyses of data in clinical
      trials. They are a critical way to assess the impact, effect or influence of key
      assumptions or variations--such as different methods of analysis, definitions of
      outcomes, protocol deviations, missing data, and outliers--on the overall
      conclusions of a study.The current paper is the second in a series of tutorial
      type manuscripts intended to discuss and clarify aspects related to key
      methodological issues in the design and analysis of clinical trials. DISCUSSION:
      In this paper we will provide a detailed exploration of the key aspects of
      sensitivity analyses including: 1) what sensitivity analyses are, why they are
      needed, and how often they are used in practice; 2) the different types of
      sensitivity analyses that one can do, with examples from the literature; 3) some
      frequently asked questions about sensitivity analyses; and 4) some suggestions on
      how to report the results of sensitivity analyses in clinical trials. SUMMARY:
      When reporting on a clinical trial, we recommend including planned or posthoc
      sensitivity analyses, the corresponding rationale and results along with the
      discussion of the consequences of these analyses on the overall findings of the
      study.

PMID- 23855339
TI  - Photoinduced charge transfer within polyaniline-encapsulated quantum dots
      decorated on graphene.
AB  - A new method to enhance the stability of quantum dots (QDs) in aqueous solution
      by encapsulating them with conducting polymer polyaniline was reported. The
      polyaniline-encapsulated QDs were then decorated onto graphene through pi-pi
      interactions between graphene and conjugated polymer shell of QDs, forming stable
      polyaniline/QD/graphene hybrid. A testing electronic device was fabricated using
      the hybrid in order to investigate the photoinduced charge transfer between
      graphene and encapsulated QDs within the hybrid. The charge transfer mechanism
      was explored through cyclic voltammetry and spectroscopic studies. The hybrid
      shows a clear response to the laser irradiation, presenting a great advantage for
      further applications in optoelectronic devices. 

PMID- 23855340
TI  - Aggregation of Alzheimer's amyloid beta-peptide in biological membranes: a
      molecular dynamics study.
AB  - Numerous studies have concluded that the interaction of the amyloid beta-peptide
      (Abeta) and cellular membranes contributes to the toxicity and cell death
      observed in the progression of Alzheimer's disease. Aggregated Abeta species
      disrupt membranes, leading to physical instability and ion leakage. Further, the
      presence of Abeta on the membrane surface increases the aggregation rate of the
      peptide, as diffusion occurs in two dimensions, increasing the probability of
      interpeptide interactions. Molecular dynamics (MD) simulations have been used to
      investigate Abeta in a number of environments, including aqueous solution and
      membranes. We previously showed that monomeric Abeta40 remains embedded in
      membranes composed of the most common lipids found in the cell membrane, but that
      the presence of ganglioside GM1 promotes release of the peptide into the
      extracellular medium. Here, we explore the interactions of two Abeta40 peptides
      in model membranes to understand whether aggregation can occur prior to the
      release of the peptide into the aqueous environment. We found that aggregation
      occurred, to different extents, in each of the model membranes and that the
      aggregates, once formed, did not exit the membrane environment. This information
      may have important implications for understanding the affinity of Abeta for
      membranes and the mechanism of Abeta toxicity in Alzheimer's disease. 

PMID- 23855341
TI  - Resource requirements for a quality Doctor of Nursing Practice program.
AB  - Fundamental to planning, implementing, and sustaining a quality Doctor of Nursing
      Practice (DNP) program is access to the resources needed to foster a learning
      environment that prepares nurses for advanced practice and leadership in the
      future redesigned health care system. This creates formidable challenges for
      schools and colleges of nursing as they endeavor to address the nation's need for
      an increased supply of advanced practice nurses to provide access to high
      quality, cost-effective care for an aging population. This article describes the
      essential resources needed to support the delivery of a DNP program and the
      proposed strategies needed to address the resource challenges.

PMID- 23855342
TI  - Scholarly publication practices of Doctor of Nursing Practice-prepared nurses.
AB  - Doctor of Nursing Practice (DNP) graduates are expected to contribute to nursing
      knowledge through empirically based studies testing the effectiveness of practice
      approaches that ultimately benefit patients and health care systems. This article
      describes publication practices of DNP graduates in the scholarly literature.
      Published studies (2005 to 2012) with at least one author with a DNP degree were
      identified. The search yielded 300 articles in 59 journals; 175 met the inclusion
      criteria and were included in this study. A codebook, consisting of 15 major
      categories, was used to extract relevant information. Original clinical
      investigations were the most frequent, followed by practice-focused patient and
      provider studies. The number of studies published in peer-reviewed journals with
      DNP-prepared authors increased over time. We recommend greater integration of
      translational science models into DNP curricula to achieve the goal of publishing
      scholarly products that use evidence to improve either practice or patient
      outcomes.

PMID- 23855343
TI  - Engaging undergraduate nursing students in research: the students' experience of
      a summer internship program pilot project.
AB  - Educators continue to struggle with ways to foster an interest in and a passion
      for nursing research among undergraduate students. The purpose of this article is
      to describe the introduction of undergraduate student internships at the Manitoba
      Centre for Nursing and Health Research, Faculty of Nursing, University of
      Manitoba, as an innovation in education that allowed students to be employed
      while engaging them in student learning, scientific inquiry, and scholarship
      through one-to-one faculty-student research mentorships. In this article, the key
      components of the summer internship program are described, along with five
      nursing students' experiences of their participation in the program.

PMID- 23855344
TI  - Student engagement and examination performance in a team-based learning course.
AB  - With calls for innovation in nursing education from national bodies of nursing,
      nurse educators must determine the best teaching strategies to meet educational
      standards. Team-based learning (TBL), an innovative teaching strategy, offers
      educators a structured, student-centered learning environment. The purpose of
      this study was to compare TBL and traditional lecture (a commonly used teaching
      method) in regard to student engagement and performance on examinations. In
      addition, the relationship between student engagement and examination scores was
      examined. Findings showed significant differences in student engagement (p <
      0.001). Analysis of examination scores indicated a significant effect within
      participants (p < 0.001). Mixed findings were found regarding the relationship
      between student engagement and examination scores. This research contributes to
      the body of knowledge related to TBL and suggests this teaching strategy is, at
      minimum, equally as effective as traditional lecture.

PMID- 23855345
TI  - Comparison of spectral estimators for characterizing fractionated atrial
      electrograms.
AB  - BACKGROUND: Complex fractionated atrial electrograms (CFAE) acquired during
      atrial fibrillation (AF) are commonly assessed using the discrete Fourier
      transform (DFT), but this can lead to inaccuracy. In this study, spectral
      estimators derived by averaging the autocorrelation function at lags were
      compared to the DFT. METHOD: Bipolar CFAE of at least 16 s duration were obtained
      from pulmonary vein ostia and left atrial free wall sites (9 paroxysmal and 10
      persistent AF patients). Power spectra were computed using the DFT and three
      other methods: 1. a novel spectral estimator based on signal averaging (NSE), 2.
      the NSE with harmonic removal (NSH), and 3. the autocorrelation function average
      at lags (AFA). Three spectral parameters were calculated: 1. the largest
      fundamental spectral peak, known as the dominant frequency (DF), 2. the DF
      amplitude (DA), and 3. the mean spectral profile (MP), which quantifies noise
      floor level. For each spectral estimator and parameter, the significance of the
      difference between paroxysmal and persistent AF was determined. RESULTS: For all
      estimators, mean DA and mean DF values were higher in persistent AF, while the
      mean MP value was higher in paroxysmal AF. The differences in means between
      paroxysmals and persistents were highly significant for 3/3 NSE and NSH
      measurements and for 2/3 DFT and AFA measurements (p<0.001). For all estimators,
      the standard deviation in DA and MP values were higher in persistent AF, while
      the standard deviation in DF value was higher in paroxysmal AF. Differences in
      standard deviations between paroxysmals and persistents were highly significant
      in 2/3 NSE and NSH measurements, in 1/3 AFA measurements, and in 0/3 DFT
      measurements. CONCLUSIONS: Measurements made from all four spectral estimators
      were in agreement as to whether the means and standard deviations in three
      spectral parameters were greater in CFAEs acquired from paroxysmal or in
      persistent AF patients. Since the measurements were consistent, use of two or
      more of these estimators for power spectral analysis can be assistive to evaluate
      CFAE more objectively and accurately, which may lead to improved clinical
      outcome. Since the most significant differences overall were achieved using the
      NSE and NSH estimators, parameters measured from their spectra will likely be the
      most useful for detecting and discerning electrophysiologic differences in the AF
      substrate based upon frequency analysis of CFAE.

PMID- 23855347
TI  - When conflicts are good: nonconscious goal conflicts reduce confirmatory
      thinking.
AB  - In this article, we argue that nonconscious goal conflicts are accompanied by a
      mindset that has wide-ranging implications for reasoning and thinking in content
      areas that are not part of the conflict itself. Specifically, we propose that
      nonconscious goal conflicts induce a mode of processing information that
      increases the likelihood of approaching an issue from opposing perspectives. This
      hypothesis is examined by investigating the effects of nonconscious goal
      conflicts on confirmatory thinking, that is, a way of thinking that narrowly
      focuses on confirmation rather than on broader examination of information. In 5
      experiments, we show that nonconscious goal conflicts significantly reduce
      confirmatory hypothesis testing (Experiments 1 through 3) and anchoring
      (Experiments 4 and 5). We further show that these effects result from a goal
      conflict by rejecting explanations based on priming of semantic opposites, and
      priming of multiple goals that do not conflict (Experiments 2 and 3), and by
      examining decision times as a conflict process variable (Experiment 5). Using
      various probes, we show that these changes in confirmatory judgments are not
      accompanied by changes in conflict phenomenology. Together, these results suggest
      that nonconscious goal conflicts attenuate the robust confirmatory thinking
      strategy that characterizes human thinking in numerous domains.

PMID- 23855346
TI  - Inequalities in self-rated health among 45+ year-olds in Almaty, Kazakhstan: a
      cross-sectional study.
AB  - BACKGROUND: Self-rated health (SRH) has been widely studied to assess health
      inequalities in both developed and developing countries. However, no studies have
      been performed in Central Asia. The aim of the study was to assess gender-,
      ethnic-, and social inequalities in SRH in Almaty, Kazakhstan. METHODS:
      Altogether, 1500 randomly selected adults aged 45 years or older were invited to
      participate in a cross-sectional study and 1199 agreed (response rate 80%). SRH
      was classified as poor, satisfactory, good and excellent. Multinomial logistic
      regression was applied to study associations between SRH and socio-demographic
      characteristics. Crude and adjusted odds ratios (OR) for poor vs. good and for
      satisfactory vs. good health were calculated with 95% confidence intervals (CI).
      RESULTS: Altogether, poor, satisfactory, good and excellent health was reported
      by 11.8%, 53.7%, 31.0% and 3.2% of the responders, respectively. Clear gradients
      in SRH were observed by age, education and self-reported material deprivation in
      both crude and adjusted analyses. Women were more likely to report poor (OR=1.9,
      95% CI: 1.2-3.1) or satisfactory (OR=1.6, 95% CI: 1.2-2.1) than good health.
      Ethnic Russians and unmarried participants had greater odds for poor vs. good
      health (OR=2.3, 95% CI: 1.5-3.7 and OR=4.0, 95% CI: 2.7-6.1, respectively) and
      for satisfactory vs. good health (OR=1.4, 95% CI: 1.1-1.9 and OR=1.9, 95% CI: 1.4
      2.5, respectively) in crude analysis, but the estimates were reduced to non
      significant levels after adjustment. Unemployed and pensioners were less likely
      to report good health than white-collar workers while no difference in SRH was
      observed between white- and blue-collar workers. CONCLUSION: Considerable levels
      of inequalities in SRH by age, gender, education and particularly self-reported
      material deprivation, but not by ethnicity or marital status were found in
      Almaty, Kazakhstan. Further research is warranted to identify the factors behind
      the observed associations in Kazakhstan.

PMID- 23855348
TI  - Monocytes circulate in constant reversible interaction with platelets in a [Ca2+]
      dependent manner.
AB  - We aimed to provide evidence that blood monocytes belonging to all subsets
      predominantly circulate in constant and usually reversible interactions with
      platelets, which are predominantly [Ca2+] dependent. The proportions of monocyte
      platelet aggregates (MPAs) attributable to individual monocyte subsets in fresh
      and promptly processed heparin-anticoagulated blood from 10 healthy subjects
      (median age 35 years, 50% male) were analysed by flow cytometry and compared to
      samples anticoagulated with a potent [Ca2+] chelator, ethylenediaminetetraacetic
      acid (EDTA). Additional experiments with [Ca2+] depletion or supplementation were
      also performed. Monocytes subsets were defined as CD14++CD16-CCR2+ cells (Mon1),
      CD14++CD16+CCR2+ cells (Mon2) and CD14+CD16++CCR2- cells (Mon3). Vast majority of
      monocytes showed aggregation with platelets in heparinised samples, but most
      monocytes were free of platelets when EDTA was used (p<0.001 for all subsets).
      Addition of the heparinised blood to EDTA-containing vacutainers reduced the
      proportion of MPAs to values seen in the directly EDTA-anticoagulated blood
      (p=0.005 for all subsets). Supplementation with CaCl2 resulted in dose-dependent
      increase in MPAs (p<0.001 for all subsets). Although the overall trend for the
      monocyte-platelet interactions was applicable to all monocyte subsets, the
      proportion of MPAs in heparinised samples was lowest for Mon3 (p<0.0001). In
      contrast, Mon3 showed the highest proportion of MPAs in EDTA-anticoagulated
      samples (p=0.004). In healthy subjects monocytes circulate in constant, but
      predominantly reversible and [Ca2+]-dependent aggregation with platelets. These
      observations may reflect a complex involvement of platelets in regulation of
      monocyte activity.

PMID- 23855349
TI  - An ion's perspective on the molecular motions of nanoconfined water: a two
      dimensional infrared spectroscopy study.
AB  - The vibrational population relaxation and hydration shell dynamics of the
      symmetric tricyanomethanide (TCM) anion are investigated in a sodium bis(2
      ethylhexyl)sulfosuccinate reverse micelle as a function of the water pool radius.
      Two-dimensional infrared (IR) spectroscopy in combination with linear absorption
      and ultrafast IR pump-probe spectroscopy is utilized in this study. Spectroscopic
      measurements show that the anion has two bands in the 2160-2175 cm(-1) region,
      each with its own spectroscopic signatures. Analysis of the vibrational dynamics
      shows that the two vibrational bands are consistent with the anion located either
      at the interface or in the water pool. The sensitivity of the TCM anion to the
      environment allows us to unequivocally monitor the vibrational and hydration
      dynamics of the anion in those two different environments. A TCM anion located at
      the interface does not show any significant variation of the vibrational dynamics
      with the water pool size. On the contrary, the TCM anion inside the water pool
      exhibits a large and nonlinear variation of the vibrational lifetime and the
      frequency-frequency correlation time with the pool radius. Moreover, for the
      solvated anion in water pools of 49 A in radius (W0 = 30), the vibrational
      lifetime reaches the values observed for the anion in bulk water while the
      frequency-frequency correlation time shows a characteristic time higher than that
      observed in the bulk. In addition, for the first time a model is developed and
      used to explain the observed nonlinear variation of the spectroscopic observables
      with the pool size. This model attributes the changes in the vibrational dynamics
      of the TCM anion in the water pool to the slow and radius-dependent water
      dynamics present in the confined environment of a reverse micelle. 

PMID- 23855350
TI  - Origin and function of the major royal jelly proteins of the honeybee (Apis
      mellifera) as members of the yellow gene family.
AB  - In the honeybee, Apis mellifera, the queen larvae are fed with a diet exclusively
      composed of royal jelly (RJ), a secretion of the hypopharyngeal gland of young
      worker bees that nurse the brood. Up to 15% of RJ is composed of proteins, the
      nine most abundant of which have been termed major royal jelly proteins (MRJPs).
      Although it is widely accepted that RJ somehow determines the fate of a female
      larva and in spite of considerable research efforts, there are surprisingly few
      studies that address the biochemical characterisation and functions of these
      MRJPs. Here we review the research on MRJPs not only in honeybees but in
      hymenopteran insects in general and provide metadata analyses on genome
      organisation of mrjp genes, corroborating previous reports that MRJPs have
      important functions for insect development and not just a nutritional value for
      developing honeybee larvae.

PMID- 23855351
TI  - Case of relapsing polychondritis showing elevation of anti-type II collagen
      antibody titer.

PMID- 23855352
TI  - Association of the rs7903146 polymorphism in transcription factor 7-like 2
      (TCF7L2) gene with gestational diabetes mellitus: a meta-analysis.
AB  - A meta-analysis was performed to assess the association between the transcription
      factor 7-like 2 (TCF7L2) gene polymorphism rs7903146 (IVS3C > T) and gestational
      diabetes mellitus (GDM). A comprehensive search was conducted to identify all
      case-control or cohort design studies of the above-mentioned associations. The
      fixed or random effect pooled measure was selected on the basis of homogeneity
      test among studies. Heterogeneity among studies was evaluated using the I(2).
      Meta-regression was used to explore the potential sources of between-study
      heterogeneity. Publication bias was estimated using Egger's linear regression
      test. A total of 10 studies including 3404 cases and 6473 controls were involved
      in this meta-analysis. Overall, after excluding articles that deviated from HWE
      in controls, and further the key contributors to between-study heterogeneity,
      significant associations between TCF7L2 rs7903146 genetic polymorphism and risk
      of gestational diabetes mellitus were observed in the dominant (OR 1.653, 95% CI
      1.416-1.930) and codominant (OR 1.525, 95% CI 1.350-1.723) models. The meta
      analysis suggests that TCF7L2 rs7903146 genetic polymorphism was associated with
      increased risk of gestational diabetes mellitus.

PMID- 23855353
TI  - Motivational interviewing: a part of the weight loss program for overweight and
      obese women prior to fertility treatment.
AB  - This is a retrospective study to investigate whether motivational interviewing
      increases weight loss among obese or overweight women prior to fertility
      treatment. Women with body mass index (BMI) > 30 kg/m(2) approaching the
      Fertility Clinic, Regional Hospital Skive, were given advice about diet and
      physical activity with the purpose of weight loss. In addition, they were asked
      if they wanted to receive motivational interviewing. Among other data, age,
      height and weight were obtained. Main outcomes were weight loss measured in kg
      and decrease in BMI. We studied 187 women: 110 received sessions of motivational
      interviewing (intervention group, n = 110), 64 received motivational support by
      phone or e-mail only and 13 women did not wish any motivational support (control
      group, n = 77). The mean weight loss and decrease in BMI was greater in the
      intervention group compared with the control group (9.3 kg versus 7.3 kg,
      difference p = 0.01, 3.3 kg/m(2) versus 2.6 kg/m(2), difference p = 0.02). The
      mean period of intervention was comparable in the two groups, 7.9 month and 7.3
      month, respectively, (difference non significant: NS). The study indicates that
      motivational interviewing may be a valuable tool in weight loss programs for
      obese and overweight women prior to fertility treatment.

PMID- 23855354
TI  - Anti-Mullerian hormone and antral follicle count for prediction of ovarian
      stimulation response in polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the ability of a combination of multiple ovarian reserve
      markers to predict ovarian stimulation response in polycystic ovary syndrome
      (PCOS). METHODS: On cycle Day 3 of 75 infertile patients with PCOS, serum
      follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian
      hormone (AMH) were measured, and antral follicle count (AFC) and ovarian volume
      (OV) were evaluated by transvaginal sonography (TVS). All patients underwent the
      same mild ovarian stimulation protocol using clomiphene citrate and highly
      purified FSH. Ovulation was monitored by TVS and confirmed by midluteal serum
      progesterone level. RESULTS: AMH, AFC, and "ovulation index" [OI, serum AMH
      (ng/ml) * bilateral AFC] were significantly lower in the ovulatory group (n = 57,
      76%) compared with the anovulatory group, whereas LH, FSH, LH/FSH ratio, and OV
      were not significantly different. Using receiver-operating characteristic curve
      analysis, the OI at a cutoff value of "85" had a sensitivity of 73.7% and a
      specificity of 72.2% in the prediction of ovulation, with an area under the curve
      of 0.733. Patients with OI < 85 had significantly higher ovulation rate (p <
      0.001). CONCLUSION: The OI, combining both AMH and AFC, is a potentially useful
      predictor of the outcome of ovarian stimulation in PCOS.

PMID- 23855355
TI  - Polycystic ovary syndrome is associated with P-wave prolongation and increased P
      wave dispersion.
AB  - BACKGROUND: The polycystic ovary syndrome (PCOS) is associated with various
      cardiac manifestations including cardiac arrhythmias. P-wave dispersion (Pdis) is
      an appealing marker for predicting the risk of developing atrial arrhythmias. The
      purpose of this study was to evaluate P-wave durations and Pdis in patients with
      PCOS. METHODS: Forty adult patients with PCOS and 46 age- and sex-matched healthy
      individuals were included in this study. P-wave maximum duration (Pmax) and P
      wave minimum duration (Pmin) were calculated on the 12-lead electrocardiogram,
      and the difference between the Pmax and the Pmin was defined as Pdis. All
      individuals also underwent transthoracic echocardiographic evaluation. RESULTS:
      Pmax and Pdis were significantly higher in patients with PCOS compared with
      controls (p = 0.007, p < 0.001, respectively). There was no difference in Pmin
      duration between both the groups (p = 0.2). Waist-to-hip ratio, insulin and
      homeostasis model assessment of insulin resistance (HOMA-IR) were higher in the
      PCOS group. Early mitral inflow deceleration time (DT) (p < 0.001) and
      isovolumetric relaxation time (p = 0.003) were longer in PCOS group. Waist-to-hip
      ratio, DT, E/A ratio and diastolic blood pressure correlated with Pdis.
      CONCLUSIONS: Patients with PCOS have prolonged Pmax and Pdis. The increase in
      those parameters may be an indicator for identification of patients at increased
      risk of atrial fibrillation.

PMID- 23855356
TI  - Distribution and morphological changes of the Golgi apparatus during Drosophila
      spermatogenesis.
AB  - In spermatogenesis, the Golgi apparatus is important for the formation of the
      acrosome, which is a sperm-specific organelle essential for fertilization.
      Comprehensive examinations of the spatiotemporal distribution and morphological
      characterizations of the Golgi in various cells during spermatogenesis are
      necessary for functional analyses and mutant screenings in the model eukaryote
      Drosophila. Here, we examined the distribution and morphology of the Golgi during
      Drosophila spermatogenesis with immunofluorescence and electron microscopy. In
      pre-meiotic germ cells, the Golgi apparatuses were distributed evenly in the
      cytoplasm. In contrast, they were located exclusively in two regions near the
      poles during the meiotic metaphase, where they were segregated prior to the
      chromosomes. In cells in anaphase to telophase, the Golgi were predominantly left
      behind in the equatorial region between the separating daughter nuclei. After
      completion of meiosis, the dispersed Golgi were assembled at the apical side of
      the spermatid nucleus to form the acrosome. Further investigation of the Golgi
      distribution in beta2-tubulin mutants showed aberrant and uneven distributions of
      the Golgi among sister cells in the meiotic spermatocytes and in the post-meiotic
      spermatids. At the ultrastructural level, the Golgi apparatus in pre-meiotic
      spermatocytes comprised a pair of stacks. The two stacks were situated adjacent
      to each other, as if they had duplicated before entering into meiotic division.
      These results highlight the dynamic nature of the Golgi during spermatogenesis
      and provide a framework for analyzing the correlations between the dynamics of
      the Golgi and its function in sperm development. 

PMID- 23855357
TI  - An immunological link between Candida albicans colonization and Crohn's disease.
AB  - The etiology of Crohn's disease (CD), an autoimmune, inflammatory bowel disease
      (IBD) which affects approximately one million people in Europe, is still unclear.
      Nevertheless, it is widely accepted that CD could result from an inappropriate
      inflammatory response to intestinal microorganisms in a genetically susceptible
      host. Most studies to date have concerned the involvement of bacteria in disease
      progression. In addition to bacteria, there appears to be a possible link between
      the commensal yeast Candida albicans and disease development. In this review, in
      an attempt to link the gut colonization process and the development of CD, we
      describe the different pathways that are involved in the progression of CD and in
      the host response to C. albicans, making the yeast a possible initiator of the
      inflammatory process observed in this IBD.

PMID- 23855358
TI  - Autotransporter-based cell surface display in Gram-negative bacteria.
AB  - Cell surface display of proteins can be used for several biotechnological
      applications such as the screening of protein libraries, whole cell biocatalysis
      and live vaccine development. Amongst all secretion systems and surface
      appendages of Gram-negative bacteria, the autotransporter secretion pathway holds
      great potential for surface display because of its modular structure and apparent
      simplicity. Autotransporters are polypeptides made up of an N-terminal signal
      peptide, a secreted or surface-displayed passenger domain and a membrane-anchored
      C-terminal translocation unit. Genetic replacement of the passenger domain allows
      for the surface display of heterologous passengers. An autotransporter-based
      surface expression module essentially consists of an application-dependent
      promoter system, a signal peptide, a passenger domain of interest and the
      autotransporter translocation unit. The passenger domain needs to be compatible
      with surface translocation although till now no general rules have been
      determined to test this compatibility. The autotransporter technology for surface
      display of heterologous passenger domains is critically discussed for various
      applications.

PMID- 23855359
TI  - Fungal degradation of lignocellulosic residues: an aspect of improved nutritive
      quality.
AB  - Microbial degradation of lignocellulosic materials brings a variety of changes in
      their bio-physicochemical properties. Lower digestibility of various agricultural
      residues can be enhanced by microbial treatment. White rot fungi are the
      potential candidates, which can improve the nutritional quality of
      lignocellulosic residues by degrading lignin and converting complex
      polysaccharides into simple sugars. Changes in physical qualities of
      lignocellulosics that is texture, colour and aroma have been an interesting area
      of study along with chemical properties. Degradation of lignocellulose not only
      upgrades the quality of degraded biomass, but helps simultaneous production of
      different commercial enzymes and other by products of interest. The review is
      focused on fungal degradation of lignocellulosics, resultant changes in
      physicochemical properties and nutritional value.

PMID- 23855360
TI  - Algal lectins as promising biomolecules for biomedical research.
AB  - Lectins are natural bioactive ubiquitous proteins or glycoproteins of non-immune
      response that bind reversibly to glycans of glycoproteins, glycolipids and
      polysaccharides possessing at least one non-catalytic domain causing
      agglutination. Some of them consist of several carbohydrate-binding domains which
      endow them with the properties of cell agglutination or precipitation of
      glycoconjugates. Lectins are rampant in nature from plants, animals and
      microorganisms. Among microorganisms, algae are the potent source of lectins with
      unique properties specifically from red algae. The demand of peculiar and
      neoteric biologically active substances has intensified the developments on
      isolation and biomedical applications of new algal lectins. Comprehensively,
      algal lectins are used in biomedical research for antiviral, antinociceptive,
      anti-inflammatory, anti-tumor activities, etc. and in pharmaceutics for the
      fabrication of cost-effective protein expression systems and nutraceutics. In
      this review, an attempt has been made to collate the information on various
      biomedical applications of algal lectins.

PMID- 23855361
TI  - When treating sport concussion, check the boxes, but also go the extra mile.

PMID- 23855362
TI  - Heating capacity of rebound shortwave diathermy and moist hot packs at
      superficial depths.
AB  - CONTEXT: The effectiveness of a new continuous diathermy unit, ReBound, as a
      heating modality is unknown. OBJECTIVE: To compare the effects of ReBound
      diathermy with silicate-gel moist hot packs on tissue temperature in the human
      triceps surae muscle. DESIGN: Crossover study. SETTING: University research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 12 healthy, college-aged
      volunteers (4 men, 8 women; age = 22.2 +/- 2.25 years, calf subcutaneous fat
      thickness = 7.2 +/- 1.9 mm). INTERVENTION(S): On 2 different days, 1 of 2
      modalities (ReBound diathermy, silicate-gel moist hot pack) was applied to the
      triceps surae muscle of each participant for 30 minutes. After 30 minutes, the
      modality was removed, and temperature decay was recorded for 20 minutes. MAIN
      OUTCOME MEASURE(S): Medial triceps surae intramuscular tissue temperature at a
      depth of 1 cm was measured using an implantable thermocouple inserted
      horizontally into the muscle. Measurements were taken every 5 minutes during the
      30-minute treatment and every minute during the 20-minute temperature decay, for
      a total of 50 minutes. Treatment was analyzed through a 2 * 7 mixed-model
      analysis of variance with repeated measures. Temperature decay was analyzed
      through a 2 * 21 mixed-model analysis of variance with repeated measures.
      RESULTS: During the 30-minute application, tissue temperatures at a depth of 1 cm
      increased more with the ReBound diathermy than with the moist hot pack (F6,66 =
      7.14, P < .001). ReBound diathermy and moist hot packs increased tissue
      temperatures 3.69 degrees C +/- 1.50 degrees C and 2.82 degrees C +/- 0.90
      degrees C, respectively, from baseline. Throughout the temperature decay, ReBound
      diathermy produced a greater rate of heat dissipation than the moist hot pack
      (F20,222 = 4.42, P < .001). CONCLUSIONS: During a 30-minute treatment at a
      superficial depth, the ReBound diathermy increased tissue temperature to moderate
      levels, which were greater than the levels reached with moist hot packs.

PMID- 23855366
TI  - Effects of CenteringPregnancy group prenatal care on breastfeeding outcomes.
AB  - INTRODUCTION: The purpose of this study was to examine the effects of
      CenteringPregnancy group prenatal care on breastfeeding outcomes, relative to
      traditional prenatal care delivered in an individual format. METHODS: A quasi
      experimental research design was conducted with 794 women receiving prenatal care
      delivered in a group or individual format at 4 sites in Tennessee. Propensity
      scores were used to create groups of women statistically matched on background
      demographics and medical history. Outcomes included breastfeeding at discharge
      and breastfeeding at postpartum follow-up. RESULTS: Compared with the matched
      comparison group of women receiving prenatal care in an individual format, women
      in CenteringPregnancy group prenatal care had significantly higher odds of any
      breastfeeding at discharge (odds ratio [OR], 2.08; 95% confidence interval [CI],
      1.32-3.26; P < .001). Across the 4 sites, there were no consistent differences in
      the odds of any breastfeeding at follow-up or exclusive breastfeeding at
      discharge or postpartum follow-up. DISCUSSION: CenteringPregnancy group prenatal
      care may have beneficial effects on initial rates of breastfeeding relative to
      individually delivered care. However, there is not sufficient evidence to
      conclude that CenteringPregnancy group prenatal care has robust effects on
      exclusive breastfeeding at discharge or postpartum follow-up.

PMID- 23855367
TI  - Risk and protective factors that distinguish adolescents who attempt suicide from
      those who only consider suicide in the past year.
AB  - Data from the 2010 Minnesota Student Survey was analyzed to identify risk and
      protective factors that distinguished adolescents across three groups: no
      suicidality, suicidal ideation only, and suicide attempt. The population-based
      sample included 70,022 students in grades 9 and 12. Hopelessness and depressive
      symptoms emerged as important risk factors to distinguish youth who reported
      suicidal ideation or behavior from those without a history of suicidality.
      However, these factors were not as important in differentiating adolescents who
      attempted suicidal from those who considered suicide but did not act on their
      thoughts. Instead, for both genders, self-injury represented the most important
      factor to distinguish these youth. Other risk factors that differentiated the
      latter groups, but not the former groups, for males were dating violence
      victimization and cigarette smoking, and for females was a same-sex sexual
      experience. Running away from home also seemed to increase the risk of a suicide
      attempt among youth in this study. Parent connectedness and academic achievement
      emerged as important protective factors to differentiate all the groups, yet
      neighborhood safety appeared to protect against the transition from suicidal
      thoughts to behavior. Findings from this study suggest risk and protective
      factors practitioners should target in clinical assessments and intervention
      programs to help prevent suicidal behavior among youth at greatest risk. 

PMID- 23855363
TI  - National Athletic Trainers' Association position statement: conservative
      management and prevention of ankle sprains in athletes.
AB  - OBJECTIVE: To present recommendations for athletic trainers and other allied
      health care professionals in the conservative management and prevention of ankle
      sprains in athletes. BACKGROUND: Because ankle sprains are a common and often
      disabling injury in athletes, athletic trainers and other sports health care
      professionals must be able to implement the most current and evidence-supported
      treatment strategies to ensure safe and rapid return to play. Equally important
      is initiating preventive measures to mitigate both first-time sprains and the
      chance of reinjury. Therefore, considerations for appropriate preventive measures
      (including taping and bracing), initial assessment, both short- and long-term
      management strategies, return-to-play guidelines, and recommendations for
      syndesmotic ankle sprains and chronic ankle instability are presented.
      RECOMMENDATIONS: The recommendations included in this position statement are
      intended to provide athletic trainers and other sports health care professionals
      with guidelines and criteria to deliver the best health care possible for the
      prevention and management of ankle sprains. An endorsement as to best practice is
      made whenever evidence supporting the recommendation is available.

PMID- 23855364
TI  - Consensus statement on concussion in sport: the 4th International Conference on
      Concussion in Sport, Zurich, November 2012.

PMID- 23855368
TI  - Purification and characterization of a hydrolysis-resistant lipase from
      Aspergillus terreus.
AB  - Lipase from Aspergillus terreus was purified to homogeneity using ammonium
      sulfate precipitation and chromatographies with Q-Sepharose and Sephacryl S-200.
      It showed a single band on SDS-PAGE and IEF-PAGE with a relative molecular mass
      of 37.2 kDa and pI of 3.2. Its glycoprotein nature was confirmed with the
      percentage of saccharides of 5.02% and 3.88% determined by the phenol/sulfuric
      acid and anthrone/ sulfuric acid methods, respectively. The lipase hydrolyzed
      both plant oils and animal oils, with the K(m) value for substrate p-NPP of 16.42
      mM at pH 6.0, 50  degrees C. The enzyme was tolerant in a wide range of pH (pH 3
      12) with optimum activity at pH 4.0. It remained stable under the highest
      temperature of 65  degrees C, with maximal activity at 50  degrees C. Ca2+, Co2+,
      Mn2+, and Ni2+ stimulated enzyme activity, but Hg2+ caused inhibition. Detected
      detergents had no obvious effect on enzyme activity, except SDS, which stimulated
      the activity at lower concentrations but inhibited the activity at higher
      concentrations. The inhibitory effect on enzyme activity of phenylmethanesulfonyl
      fluoride revealed that the Ser was involved in catalysis. Saccharides had no
      obvious effect on enzyme activity but could enhance its thermostability.
      Furthermore, the enzyme was resistant to trypsin digestion.

PMID- 23855369
TI  - Rupture of renal artery aneurysm during the early post-partum period.
AB  - Rupture of renal artery aneurysm associated with pregnancy is an uncommon
      condition. It is known that almost all previously reported cases have occurred
      during pregnancy. We experienced a case of rupture of renal artery aneurysm
      during the early post-partum period which was diagnosed by computed tomography
      and treated by angiographic embolization. To our knowledge, only two cases of
      rupture of renal artery aneurysm during the post-partum period have been reported
      in the English-language published work. An early diagnosis of rupture of renal
      artery aneurysm during the post-partum period is very challenging because the
      clinical symptoms of this condition are acute abdominal, flank or back pain,
      which are relatively common signs caused by more common post-partum
      complications. However, rupture of renal artery aneurysm is a life-threatening
      emergency condition requiring prompt diagnosis and treatment. The possibility of
      a rupture of renal artery aneurysm should be considered in any pregnant women
      with symptoms of an acute abdomen with hemorrhagic shock. 

PMID- 23855370
TI  - Why is tractable vision loss in older people being missed? Qualitative study.
AB  - BACKGROUND: There is compelling evidence that there is substantial undetected
      vision loss amongst older people. Early recognition of undetected vision loss and
      timely referral for treatment might be possible within general practice, but
      methods of identifying those with unrecognised vision loss and persuading them to
      take up services that will potentially improve their eyesight and quality of life
      are not well understood. Population screening does not lead to improved vision in
      the older population. The aim of this study is to understand why older people
      with vision loss respond (or not) to their deteriorating eyesight. METHODS: Focus
      groups and interviews were carried out with 76 people aged 65 and over from one
      general practice in London who had taken part in an earlier study of health risk
      appraisal. An analytic induction approach was used to analyse the data. RESULTS:
      Three polarised themes emerged from the groups and interviews. 1) The capacity of
      individuals to take decisions and act on them effectively versus a collection of
      factors which acted as obstacles to older people taking care of their eyesight.
      2) The belief that prevention is better than cure versus the view that
      deteriorating vision is an inevitable part of old age. 3) The incongruence
      between the professionalism and personalised approach of opticians and the
      commercialisation of their services. CONCLUSIONS: The reasons why older people
      may not seek help for deteriorating vision can be explained in a model in which
      psychological attributes, costs to the individual and judgments about normal
      ageing interact. Understanding this model may help clinical decision making and
      health promotion efforts.

PMID- 23855371
TI  - UV radiation increases carcinogenic risks for oral tissues compared to skin.
AB  - People can expose their oral cavities to UV (290-400 nm) by simply opening their
      mouths while outdoors. They can also have their oral cavities exposed to UV
      indoors to different UV-emitting devices used for diagnoses, treatments and
      procedures like teeth whitening. Because the World Health Organization declared
      UV radiation as a complete human carcinogen in 2009, we asked if oral tissues are
      at a similar or higher carcinogenic risk compared to skin tissue. To understand
      the UVB (290-320 nm)-related carcinogenic risks to these tissues, we measured
      initial DNA damage in the form of cyclobutane pyrimidine dimers (CPD), the repair
      rate of CPD (24 h) and the number of apoptotic dead cells over time resulting
      from increasing doses of erythemally weighted UV radiation. We used commercially
      available 3D-engineered models of human skin (EpiDermTM), gingival
      (EpiGingivalTM) and oral (EpiOralTM) tissues and developed an analytical approach
      for our tri-labeling fluorescent procedure to identify total DNA, CPD and
      apoptotic cells so we can simultaneously quantify DNA repair rates and dead
      cells. Both DNA repair and apoptotic cell numbers are significantly lower in oral
      cells compared with skin cells. The combined results suggest UVB-exposed oral
      tissues are at a significantly higher carcinogenic risk than skin tissues. 

PMID- 23855372
TI  - Pulmonary embolism in a patient with congenital afibrinogenemia.

PMID- 23855373
TI  - Permittivity of dielectric composite materials comprising graphene nanoribbons.
      The effect of nanostructure.
AB  - New lightweight, flexible dielectric composite materials were fabricated by the
      incorporation of several new carbon nanostructures into a dielectric host matrix.
      Both the permittivity and loss tangent values of the resulting composites were
      widely altered by varying the type and content of the conductive filler. The
      dielectric constant was tuned from moderate to very high values, while the
      corresponding loss tangent changed from ultralow to extremely high. The data
      exemplify that nanoscale changes in the structure of the conductive filler result
      in dramatic changes in the dielectric properties of composites. A microcapacitor
      model most explains the behavior of the dielectric composites. 

PMID- 23855374
TI  - Role of moesin in hyaluronan induced cell migration in glioblastoma multiforme.
AB  - BACKGROUND: A major barrier to effective treatment of glioblastoma multiforme
      (GBM) is the invasion of glioma cells into the brain parenchyma rendering local
      therapies such as surgery and radiation therapy ineffective. GBM patients with
      such highly invasive and infiltrative tumors have poor prognosis with a median
      survival time of only about a year. However, the mechanisms leading to increased
      cell migration, invasion and diffused behavior of glioma cells are still poorly
      understood. METHODS: In the current study, we applied quantitative proteomics for
      the identification of differentially expressed proteins in GBMs as compared to
      non-malignant brain tissues. RESULTS: Our study led to the identification of 23
      proteins showing overexpression in GBM; these include membrane proteins, moesin
      and CD44. The results were verified using Western blotting and
      immunohistochemistry in independent set of GBM and non-malignant brain tissues.
      Both GBM tissues and glioma cell lines (U87 / U373) demonstrated membranous
      expression of moesin and CD44, as revealed by immunohistochemistry and
      immunofluorescence, respectively. Notably, glioma cells transfected with moesin
      siRNA displayed reduced migration and invasion on treatment with hyaluronan (HA),
      an important component of the extracellular matrix in GBM. CD44, a transmembrane
      glycoprotein, acts as a major receptor for hyaluronan (HA). Using co
      immunoprecipitation assays, we further demonstrated that moesin interacts with
      CD44 in glioma cells only after treatment with HA; this implicates a novel role
      of moesin in HA-CD44 signaling in gliomas. CONCLUSIONS: Our results suggest that
      development of inhibitors which interfere with CD44-moesin interactions may open
      a new avenue in the future to mitigate cellular migration in gliomas.

PMID- 23855375
TI  - MULTIPASS, a rice R2R3-type MYB transcription factor, regulates adaptive growth
      by integrating multiple hormonal pathways.
AB  - Growth regulation is an important aspect of plant adaptation during environmental
      perturbations. Here, the role of MULTIPASS (OsMPS), an R2R3-type MYB
      transcription factor of rice, was explored. OsMPS is induced by salt stress and
      expressed in vegetative and reproductive tissues. Over-expression of OsMPS
      reduces growth under non-stress conditions, while knockdown plants display
      increased biomass. OsMPS expression is induced by abscisic acid and cytokinin,
      but is repressed by auxin, gibberellin and brassinolide. Growth retardation
      caused by OsMPS over-expression is partially restored by auxin application.
      Expression profiling revealed that OsMPS negatively regulates the expression of
      EXPANSIN (EXP) and cell-wall biosynthesis as well as phytohormone signaling
      genes. Furthermore, the expression of OsMPS-dependent genes is regulated by
      auxin, cytokinin and abscisic acid. Moreover, we show that OsMPS is a direct
      upstream regulator of OsEXPA4, OsEXPA8, OsEXPB2, OsEXPB3, OsEXPB6 and the
      endoglucanase genes OsGLU5 and OsGLU14. The multiple responses of OsMPS and its
      target genes to various hormones suggest an integrative function of OsMPS in the
      cross-talk between phytohormones and the environment to regulate adaptive growth.

PMID- 23855377
TI  - Systemic involvement of acute generalized exanthematous pustulosis: a
      retrospective study on 58 patients.
AB  - BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a severe
      cutaneous adverse reaction characterized by rash with sterile pustules, high
      fever and elevated circulating neutrophil counts. OBJECTIVES: To investigate the
      frequency and clinical features of AGEP systemic involvement. METHODS: This
      retrospective study included all patients hospitalized in our department between
      2000 and 2010 with a discharge diagnosis of AGEP. Patients had to fulfil the
      following criteria: (i) a specific EuroSCAR score > 4 and (ii) biological and
      radiological work-up available. RESULTS: Among the 58 patients enrolled, 10 had
      at least one systemic involvement: hepatic function test results were abnormal
      for seven; six had renal insufficiency; two developed acute respiratory distress,
      with one patient's bronchoalveolar lavage fluid containing many neutrophils but
      no microorganisms; one was agranulocytotic. Mean peripheral neutrophil counts and
      mean C-reactive protein levels were elevated significantly in patients with
      systemic involvement. Amoxicillin rechallenge and hospitalization duration were
      associated with systemic involvement. AGEP systemic involvement was observed in
      17% of cases studied, including liver, kidney, bone-marrow and lung involvement.
      Outcomes were favourable after drug withdrawal, and symptomatic and topical
      steroid treatments. CONCLUSIONS: The neutrophil count-systemic involvement
      association may suggest a role for neutrophils in AGEP systemic involvement.
      Physicians should be aware of the possibility of systemic involvement in AGEP and
      should actively look for signs of extracutaneous reactions.

PMID- 23855378
TI  - Indirect competitive immunoassay for detection of vitamin B2 in foods and
      pharmaceuticals.
AB  - An indirect immunoassay for the determination of vitamin B2 in food samples and
      vitamin tablets was developed. A carbodiimide-modified active ester method was
      used to synthesize the immunogen for vitamin B2. The coupling ratio of vitamin B2
      to carrier protein in immunogen was 19.98:1. The titer of the polyclonal antibody
      was 1:64000, and the antibody showed high specificity in the presence of vitamin
      B2 photolytic products and other B group vitamins. The immunoassay showed
      detection limits (LODs) of 1.07 ng/mL in PBS, 24.6 ng/g in vitamin drink, and
      0.50 mg/kg in milk powder. Recovery was 99.58-110.91% in milk powder and 70.20
      100.5% in vitamin drink. Vitamin B2 samples were analyzed by high-pressure liquid
      chromatography (HPLC) and the immunoassay, and results showed good agreement.
      Finally, this method was applied to detect vitamin B2 in commercial milk powder
      and vitamin tablets, and the detected amount correlated well with the labeled
      amount. 

PMID- 23855376
TI  - Efficacy and cost-effectiveness of a web-based and mobile stress-management
      intervention for employees: design of a randomized controlled trial.
AB  - BACKGROUND: Work-related stress is associated with a variety of mental and
      emotional problems and can lead to substantial economic costs due to lost
      productivity, absenteeism or the inability to work. There is a considerable
      amount of evidence on the effectiveness of traditional face-to-face stress
      management interventions for employees; however, they are often costly, time
      consuming, and characterized by a high access threshold. Web-based interventions
      may overcome some of these problems yet the evidence in this field is scarce.
      This paper describes the protocol for a study that will examine the efficacy and
      cost-effectiveness of a web-based guided stress-management training which is
      based on problem solving and emotion regulation and aimed at reducing stress in
      adult employees. METHODS: The study will target stressed employees aged 18 and
      older. A randomized controlled trial (RCT) design will be applied. Based on a
      power calculation of d=.35 (1-beta of 80%, alpha = .05), 264 participants will be
      recruited and randomly assigned to either the intervention group or a six-month
      waitlist control group. Inclusion criteria include an elevated stress level
      (Cohen's Perceived Stress Scale-10 >= 22) and current employment. Exclusion
      criteria include risk of suicide or previously diagnosed psychosis or
      dissociative symptoms. The primary outcome will be perceived stress, and
      secondary outcomes include depression and anxiety. Data will be collected at
      baseline and seven weeks and six months after randomization. An extended follow
      up at 12 months is planned for the intervention group. Moreover, a cost
      effectiveness analysis will be conducted from a societal perspective and will
      include both direct and indirect health care costs. Data will be analyzed on an
      intention-to-treat basis and per protocol. DISCUSSION: The substantial negative
      consequences of work-related stress emphasize the necessity for effective stress
      management trainings. If the proposed internet intervention proves to be (cost-)
      effective, a preventative, economical stress-management tool will be conceivable.
      The strengths and limitations of the present study are discussed. TRIAL
      REGISTRATION: German Register of Clinical Studies (DRKS): DRKS00004749.

PMID- 23855379
TI  - Adaptation following stroke: a personal projects analysis.
AB  - OBJECTIVES: Assessment of adaptation following stroke has tended to focus either
      on acceptance of disability or global indicators of well-being. People with
      stroke, however, tend to view adaptation in terms of reengagement with personally
      valued activities. We model the adaptation process by assessing change in
      importance, control, stress, challenge, pleasure, support and self-identification
      of personal projects (i.e., one's current activities such as work, leisure, and
      recreational activities) from prestroke to 24 months poststroke. METHOD: Personal
      projects, general health, and general well-being were assessed via interviews
      with a sample of 67 community-residing stroke survivors (39 male; mean age = 64.7
      years, SD = 13.2) on five occasions over the first 24 months poststroke. RESULTS:
      Multilevel (hierarchical) modeling of the longitudinal data indicates that
      project dimensions of Control, Stress, Challenge, Pleasure, and Support predict
      well-being in expected ways. Although projects at 6 months poststroke were rated
      as more important, stressful, challenging, and supported by others and less
      controllable and pleasurable than prestroke projects, by 12 to 18 months all
      project ratings had returned to prestroke levels, thereby suggesting successful
      adaptation. CONCLUSIONS/IMPLICATIONS: Longitudinal analysis of survivors'
      participation in valued activities poststroke revealed a pattern of adaptation
      that relates to but goes beyond that suggested by global measures of health,
      functioning, and well-being. The focus on adaptation of personal projects or
      valued activities may provide a helpful way of examining and improving well-being
      poststroke and offer new insights to inform the development of effective
      interventions for improving well-being following stroke. (PsycINFO Database
      Record (c) 2013 APA, all rights reserved).

PMID- 23855380
TI  - Older adult stroke survivors discussing poststroke depressive symptoms with a
      healthcare provider: a preliminary analysis.
AB  - PURPOSE: The purposes of this study were to examine the relationship between the
      poststroke depressive symptoms, older adult stroke survivors' perceptions of the
      depressive symptoms, and the congruence with an informal caregiver about the
      presence of depressive symptoms, and comfort talking to the health care provider
      with whether or not older stroke survivors discussed their depressive symptoms
      with a health care provider. METHOD: A cross-sectional study where 44
      caregiver/older adult stroke survivor dyads completed questionnaires including
      the Center for Epidemiologic Studies Depression Scale, Symptom Perception
      Questionnaire, and reporting of depressive symptoms to the health care provider
      via one time interview. RESULTS: Thirty-seven percent (n = 16) of all older
      stroke survivors reported depressive symptoms to their health care provider. Of
      the stroke survivors who had high levels of depressive symptoms (CESD >= 16; n =
      11), seven reported the depressive symptoms to their health care provider.
      Identifying the symptoms as possible depression and attributing the cause of the
      depressive symptoms to the stroke were related to stroke survivors reporting the
      depressive symptoms to a health care provider. CONCLUSIONS: High functioning,
      older stroke survivors may benefit from strategies to help them identify when
      they experience depressive symptoms, in order to be able to play an active role
      in their recovery by appropriately discussing their symptoms with a health care
      provider.

PMID- 23855381
TI  - Bone marrow megakaryocytes, soluble P-selectin and thrombopoietic cytokines in
      multiple myeloma patients.
AB  - The expression of adhesion molecules and other cell-surface molecules is
      substantial in the communication between plasma cells and bone marrow
      microenvironment, and may lead to increased proliferation of myeloma cells. Many
      of the cytokines involved in multiple myeloma (MM) pathogenesis, e.g.
      thrombopoietin (TPO) and interleukin-6 (IL-6), play a pivotal role in different
      developmental stages of megakaryocytopoiesis and thrombopoiesis. The principal
      aim of our study was to explore the relationship between thrombopoietic
      cytokines, megakaryocytes (MKs) and soluble P-selectin (sP-selectin) levels in MM
      patients before and after anti-angiogenic treatment. Forty-four patients (20
      female and 24 male) with a newly diagnosed MM were examined in three groups,
      following a division based on the International Staging System, ISS. Plasma
      levels of TPO, IL-6 and soluble P-selectin (human sP-selectin) were measured by
      means of ELISA. Bone marrow specimens were studied to determine the number of MKs
      and the so-called "naked nuclei" (NN), as well as the expression of platelet
      derived growth factor (PDGF). The comparison revealed a significantly higher
      concentration of cytokines and sP-selectin in newly diagnosed MM patients
      compared to healthy volunteers: for TPO, p=0.01, IL-6, p=0.0005 and sP-selectin,
      p=0.00008, respectively. Marked differences were observed in the concentration of
      sP-selectin, expression of PDGF and MKs counts between patients with MM stage I
      and MM stage III. Statistically meaningful correspondences were also found
      between MKs versus TPO, NN versus TPO, as well as MKs versus MPV, p=0.009,
      p=0.004 and p=0.0005, respectively. Furthermore, the analysis exhibited some
      statistically meaningful divergences between initial concentrations of sP
      selectin in subgroups with different response after chemotherapy. The initial
      concentration of sP-selectin in the group of MM patients with complete or partial
      remission stood at 31.86 +/- 6.13 ng/ml. In the remaining patients (stable
      disease), the concentration of sP-selectin amounted to 35.15 +/- 7.23 ng/ml
      (p=0.048). We found a correlation between sP-selectin and IL-6 (rho=0.57,
      p=0.0004), TPO and IL-6 (rho=0.46, p=0.001) as well as sP-selectin and TPO
      (rho=0.36, p=0.043), and sP-selectin and PDGF (rho=0.36, p=0.03). Our study has
      eventually demonstrated that sP-selectin, as a marker of platelet activation,
      could be a useful marker of maximum response to therapy. Its strong association
      with another marker like PDGF-AB could further lead to the development of new
      combinational therapeutic strategies of anti-angiogenic therapy in MM patients.

PMID- 23855382
TI  - Second reported case of unilateral angiokeratoma of the vulva.

PMID- 23855383
TI  - Proteomic mechanisms of cardioprotection during mammalian hibernation in
      woodchucks, Marmota monax.
AB  - Mammalian hibernation is a unique strategy for winter survival in response to
      limited food supply and harsh climate, which includes resistance to cardiac
      arrhythmias. We previously found that hibernating woodchucks (Marmota monax)
      exhibit natural resistance to Ca2+ overload-related cardiac dysfunction and
      nitric oxide (NO)-dependent vasodilation, which maintains myocardial blood flow
      during hibernation. Since the cellular/molecular mechanisms mediating the
      protection are less clear, the goal of this study was to investigate changes in
      the heart proteome and reveal related signaling networks that are involved in
      establishing cardioprotection in woodchucks during hibernation. This was
      accomplished using isobaric tags for a relative and absolute quantification
      (iTRAQ) approach. The most significant changes observed in winter hibernation
      compared to summer non-hibernation animals were upregulation of the antioxidant
      catalase and inhibition of endoplasmic reticulum (ER) stress response by
      downregulation of GRP78, mechanisms which could be responsible for the adaptation
      and protection in hibernating animals. Furthermore, protein networks pertaining
      to NO signaling, acute phase response, CREB and NFAT transcriptional regulations,
      protein kinase A and alpha-adrenergic signaling were also dramatically
      upregulated during hibernation. These adaptive mechanisms in hibernators may
      provide new directions to protect myocardium of non-hibernating animals,
      especially humans, from cardiac dysfunction induced by hypothermic stress and
      myocardial ischemia.

PMID- 23855384
TI  - Complete mitochondrial genome of Pseudorasbora elongata (Cypriniformes:
      Cyprinidae): sequencing and analysis.
AB  - In this study, the total mitochondrial genome sequence of Pseudorasbora elongata
      (Cypriniformes: Cyprinidae) was firstly determined. The genome is 16,587 bases in
      length. It consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2
      non-coding regions. These results will contribute to the natural resources
      conservation and species identification of P. elongata.

PMID- 23855385
TI  - Complete mitochondrial genome of Pelteobagrus fulvidraco (Siluriformes:
      Bagridae): genome description and related phylogenetic analyses.
AB  - Pelteobagrus fulvidraco (yellow catfish) is a small-sized species in the family
      Bagridae, order Siluriformes. In this study, we determined the complete
      mitogenome sequence of P. fulvidraco and performed phylogenetic analysis with
      closely related species. The complete mitochondrial genome of P. fulvidraco was
      16,527 bp in length, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA
      genes and 2 non-coding regions: control region (D-loop) and the origin of light
      strand replication. We inferred that five markers in mitogenome, i.e. D-loop,
      ND5, 16SrRNA, COXI and ND1, may be suitable markers for studies on population
      genetics, phylogeny, conservation genetics and evolutionary adaptation
      mechanisms.

PMID- 23855386
TI  - The importance of high distress tolerance in the relationship between nonsuicidal
      self-injury and suicide potential.
AB  - Research has indicated that nonsuicidal self-injury (NSSI) and suicidal behavior
      are strongly related to one another, with a sizable portion of individuals with a
      history of NSSI also reporting a history of nonlethal suicide attempts.
      Nonetheless, little research has examined possible moderators of this
      relationship. One potentially important construct is distress tolerance (DT),
      which has been shown to be negatively associated with NSSI and positively
      associated with the acquired capability for suicide. In this study, 93 adult
      inpatients (54.8% male) receiving treatment for substance use disorders completed
      a structured interview assessing prior suicidal behavior and questionnaires
      assessing DT, NSSI, and psychopathology. Results indicated that DT moderates the
      relationship between NSSI frequency (but not number of NSSI methods) and suicide
      potential (a continuum ranging from no prior suicidal behavior to suicidal
      behavior with minimal bodily harm to highly lethal suicidal behavior), DeltaR(2)
      = .04; p < .023; f(2) = .06, with this relation increasing in strength at higher
      levels of DT. These results are consistent with an emerging line of research
      indicating that high levels of DT facilitate suicidal behavior in at-risk
      populations and suggest that the capacity to tolerate aversive physiological and
      affective arousal might be vital to engagement in serious or lethal suicidal
      behavior.

PMID- 23855387
TI  - The results from a two-year case study of an information and communication
      technology support system for family caregivers.
AB  - PURPOSE: The aim was to better understand how information and communication
      technology (ICT) can provide support to elderly family caregivers caring for
      significant others suffering from dementia or stroke. METHOD: Ten households
      equipped with an ICT system, with a family caregiver and a spouse diagnosed with
      dementia or stroke, were followed and observed in a two-year case study. The
      family caregivers had regular meetings in groups organised by the municipal care
      of the elderly. Data from observations, semi-structured interviews, user data
      from the ICT system and data about the support provided by the municipality has
      been used to validate the findings. RESULTS: The family caregivers socialised
      with users in the group as long as the users were stayed in the group. Meetings
      in the group were an important opportunity for exchanging experiences and to
      easing one"s mind. The ICT system did not reduce the municipality"s level of
      services to the participating families. The information built into the system has
      to be constantly updated to be of interest. CONCLUSIONS: An ICT support must be
      provided in a context of personal meetings and with a formal caregiver backing.
      This will empower informal or family caregivers. Such support must give the user
      the possibility to communicate and get access to the Internet. IMPLICATIONS FOR
      REHABILITATION: Benefits were obtained when informal caregivers met with a group
      of people with whom they share the same kind of experiences and were supported by
      a formal caregiver. Informal caregivers need more attention and recognition. ICT
      systems can help but must be current and maintain the users interest.

PMID- 23855388
TI  - Women's decision making and experience of subsequent pregnancy following
      stillbirth.
AB  - INTRODUCTION: This study sought to increase understanding of women's thoughts and
      feelings about decision making and the experience of subsequent pregnancy
      following stillbirth (intrauterine death after 24 weeks' gestation). METHODS:
      Eleven women were interviewed, 8 of whom were pregnant at the time of the
      interview. Modified grounded theory was used to guide the research methodology
      and to analyze the data. RESULTS: A model was developed to illustrate women's
      experiences of decision making in relation to subsequent pregnancy and of
      subsequent pregnancy itself. DISCUSSION: The results of the current study have
      significant implications for women who have experienced stillbirth and the health
      professionals who work with them. Based on the model, women may find it helpful
      to discuss their beliefs in relation to healing and health professionals to
      provide support with this in mind. Women and their partners may also benefit from
      explanations and support about the potentially conflicting emotions they may
      experience during this time.

PMID- 23855389
TI  - Predictive markers in traumatic brain injury: opportunities for a serum
      biosignature.
AB  - The current diagnostic criteria for traumatic brain injury (TBI) are heavily
      reliant on an accurate clinical history of events. Diagnosis of mild injury
      relies on one or more of the following: confusion or disorientation, loss of
      consciousness (LOC) for 30 min or less, post-ictus amnesia for less than 24 h
      and/or other transient neurological abnormalities and a Glasgow Coma Score (GCS).
      Given the nature of the condition it is obvious that significant clinical
      challenges remain to identify in the cases of mild TBI, and additionally to grade
      more severe forms so that appropriate treatment is received. The lack of
      clinically useful biomarkers in the serum of TBI patients is a significant
      barrier to improving their outlook. Discovery of such markers would aid the
      timely diagnosis of novel and recurrent disease in a minimally invasive manner. A
      PubMed search was performed to identify studies reporting serum biomarkers in
      traumatic brain injury. Details regarding the biomarkers analysed, specificity,
      indications for outcome and statistical significance were recorded. A total of 40
      manuscripts reporting 11 biomarkers were identified in the literature. All but a
      few studies reported statistically significant differences in biomarker
      expression between groups. We conclude that serum biomarkers of TBI are an
      effective means for investigating the condition. However, the lack of novel
      markers identified in this mass of studies highlights the need to adopt new
      measure of biomarker identification.

PMID- 23855390
TI  - Acute onset of trigeminal neuralgia, facial paresis and dysphagia after mild head
      injury.
AB  - The authors report the rare and first documented case of concomitant
      microvascular decompression of trigeminal, facial and glossopharyngeal nerves for
      the management of intractable to medical therapy acute onset of trigeminal
      neuralgia, facial paresis and dysphagia after mild head injury.

PMID- 23855391
TI  - Spontaneous regression of a cystic hypoglossal schwannoma causing unilateral
      tongue atrophy.
AB  - A 60-year-old lady presented with intermittent headaches. Examination revealed
      striking marked unilateral tongue atrophy. Magnetic resonance imaging (MRI)
      revealed a cystic lesion in the hypoglossal canal and a provisional diagnosis of
      cystic hypoglossal schwannoma made. Annual surveillance scans showed stable
      appearances but surprisingly at 3 years they showed a significant reduction in
      the size of the lesion. Most patients with hypoglossal schwannomas present with
      ipsilateral hypoglossal nerve palsy; careful cranial nerve examination is vital
      in diagnosing such rare lesions. Little is known of their natural history, with
      most lesions undergoing surgery. This case highlights spontaneous regression
      following non-operative management.

PMID- 23855392
TI  - Following DNA chain extension and protein conformational changes in crystals of a
      Y-family DNA polymerase via Raman crystallography.
AB  - Y-Family DNA polymerases are known to bypass DNA lesions in vitro and in vivo.
      Sulfolobus solfataricus DNA polymerase (Dpo4) was chosen as a model Y-family
      enzyme for investigating the mechanism of DNA synthesis in single crystals.
      Crystals of Dpo4 in complexes with DNA (the binary complex) in the presence or
      absence of an incoming nucleotide were analyzed by Raman microscopy. (13)C- and
      (15)N-labeled d*CTP, or unlabeled dCTP, were soaked into the binary crystals with
      G as the templating base. In the presence of the catalytic metal ions, Mg(2+) and
      Mn(2+), nucleotide incorporation was detected by the disappearance of the
      triphosphate band of dCTP and the retention of *C modes in the crystal following
      soaking out of noncovalently bound C(or *C)TP. The addition of the second coded
      base, thymine, was observed by adding cognate dTTP to the crystal following a
      single d*CTP addition. Adding these two bases caused visible damage to the
      crystal that was possibly caused by protein and/or DNA conformational change
      within the crystal. When d*CTP is soaked into the Dpo4 crystal in the absence of
      Mn(2+) or Mg(2+), the primer extension reaction did not occur; instead, a ternary
      protein.template.d*CTP complex was formed. In the Raman difference spectra of
      both binary and ternary complexes, in addition to the modes of d(*C)CTP, features
      caused by ring modes from the template/primer bases being perturbed and from the
      DNA backbone appear, as well as features from perturbed peptide and amino acid
      side chain modes. These effects are more pronounced in the ternary complex than
      in the binary complex. Using standardized Raman intensities followed as a
      function of time, the C(*C)TP population in the crystal was maximal at ~20 min.
      These remained unchanged in the ternary complex but declined in the binary
      complexes as chain incorporation occurred. 

PMID- 23855393
TI  - Combining the UV-switchability of Keggin ions with a galvanic replacement process
      to fabricate TiO2-polyoxometalate-bimetal nanocomposites for improved surface
      enhanced raman scattering and solar light photocatalysis.
AB  - While the decoration of TiO2 surfaces with metal nanoparticles has been well
      established, the modification of the composition of metal nanoparticles
      postdeposition onto TiO2 surfaces and applicability of such bimetallic systems
      for surface enhanced Raman scattering (SERS) and photocatalysis has not hitherto
      been investigated. In this work, we, for the first time, combine the unique UV
      switchability of the Keggin ions of 12-phosphotungstic acid (PTA) to directly
      form metal nanoparticles (Ag and Cu) onto the colloidal TiO2 surface, with a
      galvanic replacement process to convert these predeposited metal nanoparticles
      into bimetallic systems (Ag/Au, Ag/Pt, Cu/Au, Cu/Pt, and Cu/Ag). We further
      demonstrate the applicability of these novel TiO2-polyoxometalate-bimetal
      nanocomposites toward improved SERS and solar light photocatalysis. 

PMID- 23855395
TI  - Commentary: symptoms of irritable bowel syndrome in patients with inflammatory
      bowel disease--organic disease or diseased organ?

PMID- 23855394
TI  - Insights into the clinical management of the syndrome of supine hypertension-
      orthostatic hypotension (SH-OH): the Irish Longitudinal Study on Ageing (TILDA).
AB  - BACKGROUND: Our previously proposed morphological classification of orthostatic
      hypotension (MOH) is an approach to the definition of three typical orthostatic
      hemodynamic patterns using non-invasive beat-to-beat monitoring. In particular,
      the MOH pattern of large drop/non-recovery (MOH-3) resembles the syndrome of
      supine hypertension-orthostatic hypotension (SH-OH), which is a treatment
      challenge for clinicians. The aim of this study was to characterise MOH-3 in the
      first wave of The Irish Longitudinal Study of Ageing (TILDA), with particular
      attention to concurrent symptoms of orthostatic intolerance (OI), prescribed
      medications and association with history of faints and blackouts. METHODS: The
      study included all TILDA wave 1 participants who had a Finometer(r) active stand.
      Automatic data signal checks were carried out to ensure that active stand data
      were of sufficient quality. Characterisation variables included demographics,
      cardiovascular and neurological medications (WHO-ATC), and self-reported
      information on comorbidities and disability. Multivariable statistics consisted
      of logistic regression models. RESULTS: Of the 4,467 cases, 1,456 (33%) were
      assigned to MOH-1 (small drop, overshoot), 2,230 (50%) to MOH-2 (medium drop,
      slower but full recovery), and 781 (18%) to MOH-3 (large drop, non-recovery). In
      the logistic regression model to predict MOH-3, statistically significant factors
      included being on antidepressants (OR = 1.99, 95% CI: 1.50 - 2.64, P < 0.001) and
      beta blockers (OR = 1.60, 95% CI: 1.26 - 2.04, P < 0.001). MOH-3 was an
      independent predictor of OI after full adjustment (OR = 1.47, 95% CI: 1.25 -
      1.73, P < 0.001), together with being on hypnotics or sedatives (OR = 1.83, 95%
      CI: 1.31 - 2.54, P < 0.001). In addition, OI was an independent predictor of
      history of falls/blackouts after full adjustment (OR = 1.27, 95% CI: 1.09 - 1.48,
      P = 0.003). CONCLUSIONS: Antidepressants and beta blockers were independently
      associated with MOH-3, and should be used judiciously in older patients with SH
      OH. Hypnotics and sedatives may add to the OI effect of MOH-3. Several trials
      have demonstrated the benefits of treating older hypertensive patients with
      cardiovascular medications that were not associated with adverse outcomes in our
      study. Therefore, the evidence of benefit does not necessarily have to conflict
      with the evidence of potential harm.

PMID- 23855396
TI  - Commentary: natural history and management of acute upper GI bleeding due to
      tumours.

PMID- 23855397
TI  - Letter: oral fructose--breath hydrogen response, symptoms, both or neither?

PMID- 23855398
TI  - Letter: fatigue, a growing concern in inflammatory bowel diseases.

PMID- 23855399
TI  - Letter: extracorporeal photopheresis in refractory chronic active ulcerative
      colitis.

PMID- 23855400
TI  - Letter: inflammatory bowel disease guidelines and conflicts of interest--authors'
      reply.

PMID- 23855401
TI  - Letter: inflammatory bowel disease guidelines and conflicts of interest.

PMID- 23855402
TI  - Alternative surgical approach for the management of uterine prolapse in young
      women: preliminary results.
AB  - AIM: To demonstrate an alternative surgical approach for the management of
      uterine prolapse in young women by a technique that was previously defined for
      post-hysterectomy vaginal vault suspension in published work and also to
      demonstrate successful operative results. METHODS: The study population consisted
      of 12 women aged 28-41 years who had stage 4 uterine prolapse and who were
      surgically treated by abdominal hysteropexy using autogenous rectus fascia
      strips. Operative results and postoperative follow-up Pelvic Organ Prolapse
      Quantification and Prolapse Quality of Life results were recorded. RESULTS: Mean
      age of patients was 35.5 +/- 4.1 years (range, 28-41). Mean parity in the study
      group was 2.6 +/- 1.0 (range, 1-5). Mean operation time was 32.0 +/- 5.2 min
      (range, 25-42). All patients were discharged on the postoperative 3rd day and no
      complications were observed postoperatively. Mean follow-up period was 20 +/- 7.0
      months (range, 12-36). All of the patients had complete remission for uterine
      prolapse and none of the patients had complaints related to the operation.
      CONCLUSION: Abdominal hysteropexy operation using rectus fascia strips provides a
      safe and alternative approach for the management of uterine prolapse in young
      women who desire to preserve their uterus. But further analysis is needed to
      confirm our results.

PMID- 23855403
TI  - Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1
      and GRIN2B affecting risk of opioid dependence.
AB  - The N-methyl-D-aspartate (NMDA) glutamate receptors play important roles in the
      pathophysiology of substance dependence (SD), but no strong genetic evidence has
      associated common variants in NMDAR-related genes to SD. We hypothesized that
      rare variants (RVs) with minor allele frequency <1% in the NMDAR-related genes
      might exert large effects on SD risk. We sequenced 34 544 bp of coding and
      flanking intronic regions of 17 genes involved in the NMDA system in 760
      subjects, all with co-occurring alcohol dependence, cocaine dependence and opioid
      dependence (OD), and 760 healthy control subjects. One hundred percent of the
      target regions were sequenced at >1000* coverage. We identified 454 variants,
      including 380 RVs. Based on case-control allele count differences, we genotyped
      11 exonic RVs in 6751 additional subjects, and the 1520 subjects from the
      sequencing stage for validation. All alleles of the 11 RVs called in the
      sequencing stage were confirmed. We found a statistically significant association
      of the 11 RVs with OD in African Americans (P = 0.00080). Results from gene-based
      association tests showed that the association signal derived mostly from DISC1 (P
      = 0.0010) and GRIN2B (P = 0.00085). DISC1 is a well-validated schizophrenia risk
      gene. This is the first demonstration that RVs affect the risk of OD and the
      first demonstration of biological convergence of schizophrenia and OD risk-via
      DISC1. 

PMID- 23855404
TI  - Treatment patterns, outcomes, and resource utilization of patients with
      metastatic melanoma in the U.K.: the MELODY study.
AB  - BACKGROUND: Advanced melanoma is an aggressive disease with a poor prognosis.
      Approved therapy is limited in the U.K. and, until recently, no treatment had
      improved survival over best supportive care. A deeper understanding of current
      clinical practice will help new agents find a place in future treatment pathways.
      OBJECTIVES: To document U.K. clinical practice for the treatment of patients with
      unresectable stage III/IV (advanced) melanoma. METHODS: MELODY (melanoma
      treatment patterns and outcomes among patients with unresectable stage III/IV
      disease: a retrospective longitudinal survey) compiled registries of consecutive
      patients with malignant melanoma (any stage) between 1 July 2005 and 30 June 2006
      from France, Italy and the U.K. Patients with advanced melanoma and >= 2 months
      of follow-up were eligible for analysis. RESULTS: There were 220 eligible
      patients identified in the U.K., of whom 117 (53.2%) received systemic therapy
      outside of clinical trials. Over half of these patients received dacarbazine as
      first- or second-line therapy. Healthcare-resource utilization was extensive and
      patients had short survival times: 1- and 2-year survival rates after first-line
      systemic treatment were 45.5% [95% confidence interval (CI) 37.1-53.6] and 24.7%
      (95% CI 17.7-32.3), respectively. CONCLUSIONS: Systemic and palliative treatments
      used to manage advanced melanoma in the U.K. are associated with considerable
      healthcare resource utilization and poor short-term survival.

PMID- 23855405
TI  - 'Someone to hold the hand over me': the significance of transpersonal
      'attachment' relationships of Danish cancer survivors.
AB  - The aim of this article is to present findings about self-reported spirituality
      of a group of Danish cancer survivors. The findings derive from a qualitative
      study that was carried out during rehabilitation week courses at a Danish
      rehabilitation centre. Methods comprised participant observation, semi-structured
      interviews and focus group interviews. Employing interpretative phenomenological
      analysis as analytical strategy, a prominent part of the informants' self
      reported spirituality was found to centre around a perceived sense of relatedness
      to a transpersonal entity that transcends the self and extends beyond spatial
      temporal boundaries. Three transpersonal entities were identified: 'God', a
      'guardian angel' and a 'deceased family member'. The key findings of the study
      demonstrate that the transpersonal entities were experienced as empowering and
      supportive resources during cancer treatment and rehabilitation and that they
      were furthermore perceived as responsible for the informants' healing and
      survival. These findings are interpreted through the lenses of two interrelated
      theoretical frameworks: Hay and Nye's approach to spirituality as 'relational
      consciousness' and Kirkpatrick and colleagues' understanding of religion and/or
      spirituality as attachment relationships. These two theoretical understandings
      are suggested as useful frameworks for capturing spiritual dimensions of cancer
      survivors' meaning making and coping in a secular society. 

PMID- 23855406
TI  - The effect of physician-based cognitive behavioural therapy among pregnant women
      with depressive symptomatology: a pilot quasi-experimental trial.
AB  - OBJECTIVE: The purpose of this pilot study is to evaluate the feasibility of a
      physician-based cognitive behavioural (CBT) intervention for the treatment of
      depressive symptomatology among pregnant women. METHODS: A pilot quasi
      experimental trial was conducted in a family practice health centre in Toronto,
      Canada. Pregnant women (n = 42) were identified as having depressive
      symptomatology according to the Edinburgh Postnatal Depression Scale (EPDS) and
      allocated to either a control group (standard prenatal) or an intervention group.
      The intervention group received standard prenatal plus brief CBT, initiated
      between the 20th and 28th gestation week prenatal visit, from their obstetrical
      physician. Follow-up assessments were conducted at 38 weeks gestation and 6 weeks
      post-partum to examine depressive symptomatology, anxiety symptomatology, health
      care utilization, medication utilization and overall treatment satisfaction.
      RESULTS: The delivery of the CBT intervention was feasible, acceptable and
      produced relatively high rates of treatment adherence. Of the 21 women in the
      intervention group who evaluated their CBT experience, 90% were satisfied.
      Although not sufficiently powered to detect differences between the study groups,
      trends in the clinical outcome data favoured the intervention group where mean
      depression and anxiety scores were lower for those who received the brief CBT
      intervention than those in the control group. CONCLUSION: Results suggest that
      brief physician-based CBT may be a feasible antenatal depression treatment
      option. The high satisfaction with, and acceptance of, the intervention by study
      participants and physicians suggests that a larger randomized trial is warranted.

PMID- 23855407
TI  - Generation of powerful tungsten reductants by visible light excitation.
AB  - The homoleptic arylisocyanide tungsten complexes, W(CNXy)6 and W(CNIph)6 (Xy =
      2,6-dimethylphenyl, Iph = 2,6-diisopropylphenyl), display intense metal to ligand
      charge transfer (MLCT) absorptions in the visible region (400-550 nm). MLCT
      emission (lambda(max) ~ 580 nm) in tetrahydrofuran (THF) solution at rt is
      observed for W(CNXy)6 and W(CNIph)6 with lifetimes of 17 and 73 ns, respectively.
      Diffusion-controlled energy transfer from electronically excited W(CNIph)6 (*W)
      to the lowest energy triplet excited state of anthracene (anth) is the dominant
      quenching pathway in THF solution. Introduction of tetrabutylammonium
      hexafluorophosphate, [Bu(n)4N][PF6], to the THF solution promotes formation of
      electron transfer (ET) quenching products, [W(CNIph)6](+) and [anth](*-). ET from
      *W to benzophenone and cobalticenium also is observed in [Bu(n)4N][PF6]/THF
      solutions. The estimated reduction potential for the [W(CNIph)6](+)/*W couple is 
      2.8 V vs Cp2Fe(+/0), establishing W(CNIph)6 as one of the most powerful
      photoreductants that has been generated with visible light.

PMID- 23855408
TI  - Growth-promoting action and growth factor release by different platelet
      derivatives.
AB  - Abstract Platelet derivatives are commonly used in wound healing and tissue
      regeneration. Different procedures of platelet preparation may differentially
      affect growth factor release and cell growth. Preparation of platelet-rich fibrin
      (PRF) is accompanied by release of growth factors, including platelet-derived
      growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming
      growth factor beta1 (TGFbeta1), and several cytokines. When compared with the
      standard procedure for platelet-rich plasma (PRP), PRF released 2-fold less PDGF,
      but >15-fold and >2-fold VEGF and TGFbeta1, respectively. Also, the release of
      several cytokines (IL-4, IL-6, IL-8, IL-10, IFNgamma, MIP-1alpha, MIP-1beta and
      TNFalpha) was significantly increased in PRF-conditioned medium (CM), compared to
      PRP-CM. Incubation of both human skin fibroblasts and human umbilical vein
      endothelial cells (HUVECs) with PRF-derived membrane (mPRF) or with PRF-CM
      enhanced cell proliferation by >2-fold (p<0.05). Interestingly, PRP elicited
      fibroblast growth at a higher extent compared to PRF. At variance, PRF effect on
      HUVEC growth was significantly greater than that of PRP, consistent with a higher
      concentration of VEGF in the PRF-CM. Thus, the procedure of PRP preparation leads
      to a larger release of PDGF, as a possible result of platelet degranulation,
      while PRF enhances the release of proangiogenic factors.

PMID- 23855409
TI  - Acute appearance of fatty acids in human plasma--a comparative study between
      polar-lipid rich oil from the microalgae Nannochloropsis oculata and krill oil in
      healthy young males.
AB  - BACKGROUND: The long-chain n-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) have human health benefits. Alternatives to fish as
      sources of EPA and DHA are needed. Oil from the micro-algae Nannochloropsis
      oculata contains a significant amount of EPA conjugated to phospholipids and
      glycolipids and no DHA. Krill oil contains EPA and DHA conjugated to
      phospholipids. We compare the appearance of fatty acids in blood plasma of
      healthy humans after consuming a high fat meal followed by either algal oil or
      krill oil. METHODS: Ten healthy males aged 18-45 years consumed a standard high
      fat (55 g) breakfast followed by either algal oil (providing 1.5 g EPA and no
      DHA) or krill oil (providing 1.02 g EPA and 0.54 g DHA). All participants
      consumed both oils in random order and separated by 7 days. Blood samples were
      collected before the breakfast and at several time points up to 10 hours after
      taking the oils. Fatty acid concentrations (MUg/ml) in plasma were determined by
      gas chromatography. RESULTS: Fatty acids derived mainly from the breakfast
      appeared rapidly in plasma, peaking about 3 hours after consuming the breakfast,
      and in a pattern that reflected their content in the breakfast. There were time
      dependent increases in the concentrations of both EPA and DHA with both algal oil
      (P < 0.001 for EPA; P = 0.027 for DHA) and krill oil (P < 0.001 for both EPA and
      DHA). The concentration of EPA was higher with algal oil than with krill oil at
      several time points. DHA concentration did not differ between oils at any time
      point. The maximum concentration of EPA was higher with algal oil (P = 0.010) and
      both the area under the concentration curve (AUC) and the incremental AUC for EPA
      were greater with algal oil (P = 0.020 and 0.006). There was no difference
      between oils in the AUC or the incremental AUC for DHA. CONCLUSION: This study in
      healthy young men given a single dose of oil indicates that the polar-lipid rich
      oil from the algae Nannochloropis oculata is a good source of EPA in humans.

PMID- 23855410
TI  - Structural and photosensitizing features of phthalocyanine--zeolite hybrid
      nanomaterials.
AB  - In this work, we have quantified for the first time the fluorescence and singlet
      oxygen quantum yields of a silicon(IV) phthalocyanine bound to the surface of
      zeolite L nanocrystals. The photophysical properties were correlated with the
      absorption spectra and the morphology of the nanoparticles, and most importantly,
      with the fraction of photoactive chromophores. By comparison with the
      fluorescence and singlet oxygen quantum yields of the free phthalocyaninate in
      dilute solution (PhiF = 0.50 and Phi? = 0.50, respectively), we conclude that for
      the most efficient nanoparticles nearly 80% of chromophores are active as
      monomeric units on the surface, as indicated by the corresponding quantum yields
      (PhiF = 0.40 and Phi? = 0.40). We further functionalized and raised the zeta
      potential of the best performing nanomaterial to improve its water
      dispersibility. The functionalization was monitored by thermogravimetric analysis
      and time-of-flight secondary-ion mass spectrometry, and its influence on the
      photophysical properties was assessed. The resulting nanomaterials are capable of
      establishing stable suspensions in water while retaining the ability to form
      reactive oxygen species upon irradiation with red light. This provides a basis
      for the rational design of photoactive nanomaterials for photodynamic therapy or
      water decontamination.

PMID- 23855411
TI  - Prolonged fecal shedding of 'megabacteria' (Macrorhabdus ornithogaster) by
      clinically healthy canaries (Serinus canaria).
AB  - Macrorhabdus ornithogaster, often referred to as 'megabacterium', is an
      ascomycetous yeast usually found colonizing the mucosal surface of the isthmus
      existing between the glandular and grinding stomach of a wide diversity of bird
      species. However, this yeast can also behave as an avian pathogen, therefore
      representing a potential threat to bird breeding. The aim of this work was to
      assess the prevalence and patterns of fecal shedding of M. ornithogaster in a
      colony of healthy canary birds (Serinus canaria) bred in captivity. Fresh fecal
      samples from 39 canaries (17 males and 22 females) were cultured in liquid media
      for M. ornithogaster enrichment. Only two clinically healthy females were fecal
      culture-positive for the yeast, which represents an overall prevalence of 5.13%
      in the sampled population. A close surveillance of the two culture-positive
      canaries, which included periodical microscopic examination of fresh stool
      samples, showed prolonged fecal shedding of M. ornithogaster. Nevertheless, both
      animals remained asymptomatic throughout the study period. To the best of our
      knowledge, this is the first study reporting the continuous shedding of M.
      ornithogaster by clinically healthy canaries.

PMID- 23855412
TI  - Invasive infections due to Candida norvegensis and Candida inconspicua: report of
      12 cases and review of the literature.
AB  - Candida inconspicua and Candida norvegensis are two closely related species
      rarely involved in invasive infections. The purpose of this study was to depict
      the epidemiologic and clinical characteristics of candidemia due to these
      emerging fluconazole less susceptible species. A retrospective analysis of the
      epidemiology of C. inconspicua and C. norvegensis during the period 2006-2010 was
      initiated in six French University hospitals. From this, demographics, clinical,
      diagnostic and therapeutic data of C. inconspicua or C. norvegensis candidemia
      were recorded and compared to the observations reported in the literature. C.
      inconspicua was more frequently isolated compared to C. norvegensis (ratio 2.6)
      but from the same preferential body sites: mainly digestive (56.4% and 48.37%,
      respectively, for C. inconspicua and C. norvegensis) and respiratory (26% and
      28.2%, respectively). Thirteen cases of candidemia were recorded and five
      additional cases were found in the literature. Hematogical malignancy was the
      main underlying disease (n = 12). Associated factors were the presence of a
      vascular catheter (n = 18), broad-spectrum antibiotics (n = 15), and neutropenia
      (n = 14). In 13 cases (72%), prior colonization was noted before the candidemia
      diagnosis. Combining the results for the two species, Minimal Inhibitory
      Concentrations (MIC50) of amphotericin B, fluconazole, voriconazole and
      caspofungin were 0.125, 48, 0.25, and 0.19 mg/l, respectively. These two species
      must be added to the growing list of emerging Candida species poorly susceptible
      to fluconazole.

PMID- 23855413
TI  - Body composition assessment in overweight women: validation of air displacement
      plethysmography.
AB  - PURPOSE: The purpose of this study was to evaluate the validity and reliability
      of air displacement plethysmography (ADP) compared to a dual energy x-ray
      absorptiometry (DXA) criterion for body composition measurement in overweight and
      obese women (BMI >= 25.0 kg m(2) ). SUBJECTS/METHODS: Twenty-four overweight and
      obese women (Mean +/- SD; Age: 36.6 +/- 12.0 years; Height: 166.4 +/- 5.8 cm;
      Weight: 86.5 +/- 14.2 kg; Body Fat: 38.5 +/- 3.7%; BMI: 31.3 +/- 5.5 kg m(2) )
      were tested after an 8-h fast. Fat mass (FM), fat-free mass (FFM) and percent
      body fat (%BF) were measured by ADP and compared to values determined by the DXA
      criterion. FFM from DXA was calculated as lean mass plus bone mineral content. A
      paired samples t-test was used to test for significant differences in the body
      composition variables between methods. A one-way ANOVA along with intraclass
      correlation coefficient (ICC), SEM,%SEM and MD was used to represent reliability.
      RESULTS: Validity data comparing ADP and DXA demonstrated no significant
      difference in FM (ADP-DXA FM = 0.99 kg; P = 0.113), FFM (0.98 kg; P = 0.115) and
      %BF (1.56%; P = 0.540). Reliability data for ADP between the first and second
      trials showed no significant difference in FM (P = 0.168; ICC = 0.994; SEM =
      0.668), FFM (P = 0.058; ICC = 0.973; SEM = 0.892) or %BF (P = 0.121; ICC = 0.971;
      SEM = 0.813). CONCLUSIONS: For overweight and obese women, ADP was found to be a
      valid measure of FM, FFM and %BF when compared with DXA. The reliability of ADP
      was supported for all body composition variables.

PMID- 23855414
TI  - Quantitative analysis of serum IgG galactosylation assists differential diagnosis
      of ovarian cancer.
AB  - CA-125, the most frequently used biomarker for ovarian cancer detection, cannot
      provide accurate diagnosis due to its poor specificity as it may also increase in
      many benign gynecological conditions. Thus, reducing the false-positive outcomes
      is urgently needed. Decrease in terminal galactosylated N-glycans of serum IgG
      has been found in various malignancies compared to healthy controls. Here, this
      alteration of IgG galactosylation was extended to be investigated between ovarian
      cancer and benign conditions with similar elevated CA-125 levels, in an attempt
      to effectively distinguish between false-positive subjects and ovarian cancer
      patients. In the study of 58 patients with elevated CA-125 levels (>35 U/mL), the
      degree of IgG galactosylation was measured from the relative intensities of IgG
      digalactosyl (G2), monogalactosyl (G1), and agalactosylated (G0) N-glycans
      according to the formula G0/(G1+G2.2). This ratio was found significantly higher
      in the malignant group than in the benign group (0.74 vs 0.34; p<0.0001). ROC
      analysis demonstrated an improved specificity from 65.2% (by CA-125 test alone)
      to 84.6%, while maintaining sensitivity at 90% by incorporating quantitative
      analysis of IgG galactosylation in the current assay. The results suggest that
      combining quantitative alteration of IgG galactosylation with CA-125 may generate
      an overall more robust approach for differential diagnosis of ovarian cancer.

PMID- 23855415
TI  - A cluster randomized trial to evaluate the efficacy of a school-based behavioral
      intervention for health promotion among children aged 3 to 5.
AB  - BACKGROUND: The onset of inadequate behaviors leading to the development of risk
      factors for chronic diseases is known to occur early in life. An effective
      program for health promotion should therefore focus on children and their
      environment, as the starting point for behavior development. The overarching
      objective of the Program SI! (Salud Integral - Comprehensive Health) is to
      intervene at the school level, to establish and develop life-lasting habits that
      will help preserving health during adulthood. The Program SI! comprises five
      consecutive subprograms according to the five stages of education in Spain, the
      first being in preschoolers. This study aims to evaluate the efficacy of Program
      SI! to establish and improve lifestyle behaviors in children (preschoolers aged 3
      5 years), their parents, and teachers, and also improving the school environment.
      A secondary objective is to evaluate improvements in cardiovascular health
      related markers (anthropometric parameters, blood pressure, and dietary and
      physical activity patterns) in these same children. METHODS/DESIGN: 24 public
      schools from the city of Madrid (Spain) were allocated through stratified
      randomization to intervention or control. The intervention schools follow the
      Program SI!, which provides didactic units, emotions cards, healthy tips, and
      online resources. The intervention schools integrate the Program SI! into their
      scholar curriculum organized in four complete weeks during each academic year
      during the 3 years of preschool education. Control schools follow their normal
      curriculum. Primary outcomes are 1-year, and 3-year changes from baseline of
      scores for knowledge, attitudes, and habits (KAH) of children, their parents and
      teachers in regards to a healthy lifestyle. Secondary outcomes are 1-year, and 3
      year changes from baseline in clinical and anthropometric parameters of children.
      DISCUSSION: The Program SI! is a long-term health promotion program starting in 3
      years old. It incorporates the traditional areas of intervention (diet and
      physical activity), introducing additional components such as knowledge of the
      human body and management of emotions to achieve a comprehensive intervention.
      The Program SI! is designed to be an effective, sustainable health promotion
      program for the adoption of healthy behaviors from early in life. TRIAL
      REGISTRATION:  TRIAL REGISTRATION NUMBER: NCT01579708.

PMID- 23855417
TI  - Preparation and characterization of nonaqueous proton-conducting membranes with
      protic ionic liquids.
AB  - Hybrid Nafion membranes were successfully fabricated by incorporating with protic
      imidazolium ionic liquids 1-(2-aminoethyl)-3-methylimidazolium chloride
      ([MimAE]Cl), 1-(2-hydroxylethyl)-3-methylimidazolium chloride ([MimHE]Cl), and 1
      carboxylmethyl-3-methylimidazolium chloride ([MimCM]Cl) for high-temperature fuel
      cells. The composite membranes were characterized by impedance spectroscopy,
      small-angle X-ray scattering (SAXS), scanning electronic microscopy (SEM), and
      thermogravimetric analysis (TGA). The incorporated protic ionic liquids enhance
      the doping of phosphoric acid (PA) and result in a relatively high ionic
      conductivity. The Nafion/10 wt % [MimAE]Cl/PA composite membrane exhibits an
      ionic conductivity of 6.0 mS/cm at 130  degrees C without humidification.
      [MimAE]Cl can swell the Nafion matrix more homogeneously than [MimHE]Cl or
      [MimCM]Cl, which results in a better ionic conductivity. It is notable that the
      composite Nafion/IL/PA membranes have a better thermal stability than the
      pristine Nafion membranes. 

PMID- 23855416
TI  - Working memory in nonsymbolic approximate arithmetic processing: a dual-task
      study with preschoolers.
AB  - Preschool children have been proven to possess nonsymbolic approximate arithmetic
      skills before learning how to manipulate symbolic math and thus before any formal
      math instruction. It has been assumed that nonsymbolic approximate math tasks
      necessitate the allocation of Working Memory (WM) resources. WM has been
      consistently shown to be an important predictor of children's math development
      and achievement. The aim of our study was to uncover the specific role of WM in
      nonsymbolic approximate math. For this purpose, we conducted a dual-task study
      with preschoolers with active phonological, visual, spatial, and central
      executive interference during the completion of a nonsymbolic approximate
      addition dot task. With regard to the role of WM, we found a clear performance
      breakdown in the central executive interference condition. Our findings provide
      insight into the underlying cognitive processes involved in storing and
      manipulating nonsymbolic approximate numerosities during early arithmetic. 

PMID- 23855418
TI  - Treatment of facial paraffinoma with a bipolar radiofrequency device.

PMID- 23855419
TI  - Attenuation of histamine-induced airway effects by intranasal application of
      levocetirizine in mice.
AB  - The present study was performed to investigate the histamine-induced airway
      effect of levocetirizine, an active enantiomer of cetirizine, by intranasal
      application using ddY mice. Nasal rubbing and sneezing after histamine
      application into the nasal cavity were used as an index of histamine-induced
      airway effect in mice. Intranasal application of levocetirizine inhibited both
      nasal rubbing and sneezing concentration-dependently, and the ED50 values were
      0.62 (0.51-0.77) and 0.70 (0.51-1.02) %/site for nasal rubbing and sneezing,
      respectively. ED50 values of cetirizine were 1.24 (1.02-1.59) and 1.35 (1.02
      2.08) %/site for nasal rubbing and sneezing, respectively. Levocetirizine also
      inhibited nasal rubbing and sneezing when administered orally. These results
      clearly indicate that levocetirizine was about two times more potent than
      cetirizine by intranasal application, similar to the findings of the former's
      affinity for human histamine H1 receptors. In addition, the present findings
      raise the expectation of the development of levocetirizine nasal drops.

PMID- 23855420
TI  - Adherence to anticoagulant treatment with dabigatran in a real-world setting.
AB  - BACKGROUND: In clinical trials, adherence to a prescribed regimen with dabigatran
      was enhanced by frequent follow-up visits and pill counts. OBJECTIVES: To
      describe the experience of dabigatran treatment in clinical practice, focusing on
      adherence. PATIENTS/METHODS: In a cross-sectional cohort study, we interviewed
      103 patients treated for at least 3 months with dabigatran and followed by our
      anticoagulant clinic. We obtained information on the number of capsules of
      dabigatran dispensed by the pharmacy of each patient covering the entire
      treatment period and calculated the adherence. In addition, information on the
      frequency of missed capsules, bleeding, thromboembolic events and other adverse
      events, specifically dyspepsia, was captured from the interviews and medical
      records. RESULTS: The mean age was 75.5 (+/- 8.5) years, 46% were females, and
      the mean CHADS2 score was 2.5. Dispensation data were obtained for 99 patients
      and adherence was 99.7% (median; interquartile range 94.6%-100%) with 11 patients
      showing < 80% adherence. During their interview, 31 patients (30%) acknowledged
      that they sometimes had missed taking the medication, ranging from 'twice in 6
      years' to 'every day'. One additional patient with adherence < 80% was
      identified. Twenty-one patients (20%) reported bleeding complications, two of
      which were major; one patient had an ischemic stroke and 34 (33%) reported some
      degree of dyspepsia. There were no significant differences in the results between
      RE-LY study-experienced and study-naive patients. CONCLUSION: In our clinical
      practice adherence to the twice-daily dabigatran regimen was generally good,
      although 12% of the patients had an inadequate adherence. Routine feedback from
      the pharmacies could inform the physician to improve the anticoagulant
      management.

PMID- 23855421
TI  - Combat health care providers and resiliency: adaptive coping mechanisms during
      and after deployment.
AB  - The purpose of this investigation was to understand the varied health care
      provider responses to traumas by identifying perceptions of control and self
      efficacy, appraisal styles, and postevent coping strategies in active duty
      military nurses and physicians deployed to combat/terrorist regions. Twenty
      purposively sampled military health care providers completed a descriptive
      questionnaire, the Posttraumatic Stress Disorder Checklist, the General Self
      Efficacy Scale, and a recorded semistructured interview that was later
      transcribed and content analyzed. Cognitive-behavioral determinants of healthy
      response to trauma were used to frame this descriptive interpretive study and to
      assist with developing a model for healthy adaptation in trauma-exposed health
      care providers. Participants felt they had the greatest control over their health
      care provider role in theater, and most expressed a belief that a sense of
      control and a sense of purpose were important to their coping. All used some form
      of social support to cope and many found calming activities that allowed for self
      reflection to be helpful. Results from this analysis can be used to inform
      interventions and promote postevent coping behaviors that increase social
      support, strengthen important bonds, and enhance involvement in activities that
      elicit positive emotions. Health care providers experienced positive outcomes
      despite considerable traumatic exposure by using coping strategies that map
      closely to several principles of psychological first aid. This suggests a need to
      train all medical personnel in these concepts as they appear helpful in
      mitigating responses to the stress of combat-related exposures.

PMID- 23855422
TI  - Personality Assessment Questionnaire as a pre-accession screen for risk of mental
      disorders and early attrition in U. S. Army recruits.
AB  - Personality assessment tools have been studied as predictors of performance in
      civilian and military work settings. The Tailored Adaptive Personality Assessment
      System (TAPAS) was developed to improve selection of new military recruits by
      predicting motivational outcomes such as job effort, physical fitness, and drive
      to perform at high standards. The purpose of this study is to examine the utility
      of TAPAS as a predictor of psychiatric morbidity and early discharge in a sample
      of 15,082 Army, active duty, enlisted, nonprior service recruits. Associations
      between TAPAS personality dimension score quintiles and mental disorder
      diagnoses, attrition, and health care utilization in United States Army recruits
      who took TAPAS in the fiscal year 2010 were analyzed using multivariate logistic
      regression and log-linear modeling. TAPAS physical conditioning dimension scores
      were predictive of mental disorder diagnosis and attrition, with TAPAS scorers in
      the lowest quintile at increased odds of early discharge (odds ratio [OR]: 2.08,
      95% CI 1.73, 2.51), mental disorder diagnosis (OR: 1.41, 95% CI 1.20, 1.66) and
      greater mental health care utilization (1.61, 95% CI 1.46, 1.78) compared with
      TAPAS scorers in the highest quintile. Results indicated that TAPAS may have an
      important use as a mental health fitness screening tool for those who wish to
      serve in the military by identifying a limited high risk group of applicants for
      mental health diagnostic evaluation. TAPAS may augment current cognitive and
      educational screens and potentially reduce the burden of mental disorders and
      premature attrition.

PMID- 23855423
TI  - Changing profile of rotavirus genotypes in Bangladesh, 2006-2012.
AB  - BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants and
      young children worldwide including Bangladesh. Unlike what was seen in high
      income countries, the licensed rotavirus vaccines did not show high efficacy in
      Bangladeshi trials. We assessed rotavirus prevalence and genotypes in Bangladesh
      over six-year period to provide baseline information on the rotavirus burden and
      changing profile in the country. METHODS: This study was conducted from June 2006
      to May 2012 in Matlab, Bangladesh. Group A rotaviruses were detected in stools
      collected from diarrhea patients by ELISA and genotyped using multiplex reverse
      transcription PCR followed by nucleotide sequencing. RESULTS: Of the 9678 stool
      samples, 20.3% were positive for rotavirus. The most predominant genotype was
      G1P[8] (22.4%), followed by G9P[8] (20.8%), G2P[4] (16.9%) and G12P[8] (10.4%).
      Mixed infections were detected in 14.2% of the samples. Emergence of an unusual
      strain, G9P[4] was documented during 2011-12. Several amino acid mismatches in
      the antigenic epitopes of VP7 and VP4 between Bangladeshi and the vaccine strains
      were identified. CONCLUSIONS: Our study provides important information on
      rotavirus genotypes that should be considered for the selection and introduction
      of rotavirus vaccines in Bangladesh.

PMID- 23855424
TI  - 2013 European Society of Hypertension/European Society of Cardiology Hypertension
      Guidelines.

PMID- 23855425
TI  - The course of inflammatory bowel disease during pregnancy and postpartum: a
      prospective European ECCO-EpiCom Study of 209 pregnant women.
AB  - BACKGROUND: The impact of pregnancy on the course of IBD is still controversial.
      AIM: To investigate the impact of pregnancy on IBD and to search for factors with
      potential impact on remission. METHODS: Pregnant IBD women from 12 European
      countries were enrolled between January 2003 and December 2006 and compared at
      conception (1:1) with nonpregnant IBD women. Data on disease course were
      prospectively collected at each trimester during pregnancy and in the postpartum
      (6 months) using a standardised questionnaire. RESULTS: A total of 209 pregnant
      IBD women were included: 92 with Crohn's disease (CD; median age 31 years, range
      17-40) and 117 with ulcerative colitis (UC; median age 32 years, range 19-42). No
      statistically significant difference in disease course during pregnancy and
      postpartum was observed between pregnant and nonpregnant CD women. Longer disease
      duration in CD and immunosuppressive therapy were found to be risk factors for
      activity during pregnancy. Pregnant UC women were more likely than nonpregnant UC
      women to relapse both during pregnancy (RR 2.19; 95% CI: 1.25-3.97, 0.004) and
      postpartum (RR 6.22; 95% CI: 2.05-79.3, P = 0.0004). During pregnancy, relapse
      was mainly observed in the first (RR 8.80; 95% CI 2.05-79.3, P < 0.0004) and the
      second trimester (RR 2.84, 95% CI 1.2-7.45, P = 0.0098). CONCLUSIONS: Pregnant
      women with Crohn's disease had a similar disease course both during pregnancy and
      after delivery as the nonpregnant women. In contrast, pregnant women with
      ulcerative colitis were at higher risk of relapse during pregnancy and in the
      postpartum than nonpregnant ulcerative colitis women.

PMID- 23855426
TI  - Evaluation of topical black seed oil in the treatment of allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is the most common manifestation of atopic
      reaction to inhaled allergens. It is a chronic inflammatory disease which may
      first appear at any age, but the onset is usually during childhood or
      adolescence. Up to date there is no curative treatment for this disorder and most
      of the drugs that were used for treatment only can induce symptomatic relief and
      some of them have side effect and can cause withdrawal symptoms. OBJECTIVE: To
      evaluate the therapeutic efficacy of the Nigella sativa (NS) extract as treatment
      approach for allergic rhinitis. PATIENTS & METHODS: A total of 68 patients with
      AR were included in the study, of them 19 patients were with mild symptoms, 28
      patients were with moderate symptoms and 21 patients were with severe symptoms.
      Each group was subdivided into active and control subgroups. To prove that the
      patient's symptoms were allergic in nature, skin test was performed for all
      patients. Any individual with negative skin test was excluded. The individuals in
      the active group received N. sativa oil and the control group individuals
      received ordinary food oil in the form of nasal drops for 6 weeks. RESULTS: After
      the 6 weeks treatment course, 100% of the patients in the mild active group
      became symptoms free; while in moderate active group 68.7% became symptoms free
      and 25% were improved; while in severe active group 58.3% became symptoms free
      and 25% were improved. In addition, 92.1% of total patients in the active group
      demonstrated improvement in their symptoms or were symptoms free, while the
      corresponding value was 30.1% in the control group (P=0.000). At the end of 6
      weeks of treatment with topical use, the improvement in tolerability of allergen
      exposure in active group became 55.2% which was significant (P=0.006) as compared
      with control group which was accounted for 20% at the same time. CONCLUSION:
      Topical application of black seed oil was effective in the treatment of allergic
      rhinitis, with minimal side effects.

PMID- 23855427
TI  - Microbial production and chemical transformation of poly-gamma-glutamate.
AB  - Poly-gamma-glutamate (PGA), a novel polyamide material with industrial
      applications, possesses a nylon-like backbone, is structurally similar to
      polyacrylic acid, is biodegradable and is safe for human consumption. PGA is
      frequently found in the mucilage of natto, a Japanese traditional fermented food.
      To date, three different types of PGA, namely a homo polymer of D-glutamate (D
      PGA), a homo polymer of L-glutamate (L-PGA), and a random copolymer consisting of
      D- and L-glutamate (DL-PGA), are known. This review will detail the occurrence
      and physiology of PGA. The proposed reaction mechanism of PGA synthesis including
      its localization and the structure of the involved enzyme, PGA synthetase, are
      described. The occurrence of multiple carboxyl residues in PGA likely plays a
      role in its relative unsuitability for the development of bio-nylon plastics and
      thus, establishment of an efficient PGA-reforming strategy is of great
      importance. Aside from the potential applications of PGA proposed to date, a new
      technique for chemical transformation of PGA is also discussed. Finally, some
      techniques for PGA and its derivatives in advanced material technology are
      presented.

PMID- 23855429
TI  - Compromised approximate number system acuity in school-aged children born
      extremely preterm.

PMID- 23855428
TI  - The clinical significance of BRAF and NRAS mutations in a clinic-based metastatic
      melanoma cohort.
AB  - BACKGROUND: BRAF and NRAS mutations are frequently found in melanoma tumours, and
      recently developed BRAF-targeted therapies demonstrate significant clinical
      benefit. OBJECTIVES: We sought to investigate the clinical significance of BRAF
      and NRAS mutations in a clinic-based metastatic melanoma cohort. METHODS: In
      total, 237 tumours, mostly metastatic lesions, from 203 patients were screened
      for mutations in exon 15 of BRAF and exon 2 of NRAS using Sanger sequencing. BRAF
      and NRAS mutation status was analysed in relation to clinical and
      histopathological characteristics, and outcome. RESULTS: Mutation in BRAF and
      NRAS was present in 43% (88% V600E, 10% V600K) and 30% (48% Q61K, 40% Q61R) of
      metastatic melanomas, respectively. We found consistent BRAF and NRAS mutation
      status in all but one of 27 patients with multiple metastases. BRAF mutation was
      associated with younger age at primary diagnosis (P = 0.02). Among patients with
      distant metastatic melanoma, patients with BRAF-mutant tumours without BRAF
      inhibitor treatment had inferior survival compared with patients with BRAF
      inhibitor treatment [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.10
      5.01, P = 0.03]. We also observed a trend towards better prognosis for patients
      with wild-type and NRAS-mutant tumours compared with BRAF V600E-mutant tumours
      (HR 0.64, 95% CI 0.39-1.04, P = 0.07; and HR 0.76, 95% CI 0.48-1.21, P = 0.25,
      respectively). CONCLUSIONS: We were able to confirm the effect of BRAF inhibitor
      treatment in a single clinical institution. The results suggest further that BRAF
      mutation is a weak prognostic factor but a strong predictive factor and that BRAF
      mutant melanoma might constitute one or more distinct subtypes of the disease
      with certain aetiology and clinical outcome.

PMID- 23855430
TI  - Detection of Hanganutziu-Deicher antigens in O-glycans from pig heart tissues by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - BACKGROUND: In the alpha1,3-galactosyltransferase knockout (alpha-GalT KO) pig
      era, identification of the non-Gal epitopes is necessary for successful pig-to
      human xenotransplantation. Recently, we successfully detected alpha-Gal epitopes
      as well as Hanganutziu-Deicher (H-D) antigens from the N-glycans in the pig heart
      tissues, which have been considered as promising non-Gal antigens. However, the
      profiling of O-glycan from pig heart tissues had not been performed owing to the
      difficulty of O-glycan preparation. METHODS: In this study, we established the
      simple and sensitive method to profile O-glycans from pig heart aortic valve,
      aortic wall, pulmonary valve, pulmonary wall, and cardiac muscle tissues. To
      liberate O-glycans from the pig heart tissues, we used non-reductive beta
      elimination reagent and subsequently purified the glycans. After permethylation,
      the glycans were qualitatively analyzed by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS:
      The comprehensive O-glycan analysis method was successfully validated using model
      glycoproteins such as bovine serum fetuin (BSF) and bovine submaxillary gland
      mucin (BSM) glycoproteins, and their O-glycan profiles were in accordance with
      the data of previous studies. Next, we applied the method for O-glycan release
      and characterization to analysis of various pig heart tissues. As a result, total
      39, 33, 24, 36, and 25 of O-glycans were detected from aortic valve, aortic wall,
      pulmonary valve, pulmonary wall, and cardiac muscle, respectively. Furthermore,
      four in aortic valve, one in aortic wall, one in pulmonary valve, one in
      pulmonary wall, and one in cardiac muscle were particularly determined as
      terminally N-glycolylneuraminic acid-linked O-glycans, which is considered to be
      the H-D antigens. CONCLUSIONS: Here, we initially described the O-glycan
      structures of various pig heart tissues, and additionally, the existence of H-D
      antigen type O-glycans was firstly identified. These results will be fundamental
      information for overcoming the xenoantigenic carbohydrate-related immunological
      rejection in pig-to-human heart tissue xenotransplantation.

PMID- 23855431
TI  - Can mean platelet volume levels of trauma patients predict severity of trauma?
AB  - Abstract In this study, we aimed to evaluate the mean platelet voulme (MPV)
      levels of trauma patients who were admitted to our emergency department. Of the
      total 232 trauma patients, 40 females and 192 males over the age of 18 years were
      included in this study. Of them, 102 patients were mild trauma [Glasgow Coma
      Scale (GCS) 15-13)], 40 patients were moderate (GCS 12-9) and 90 patients were
      severe trauma (GCS 8-3) patients. We also calculated the Revised Trauma Score
      (RTS) of the patients. MPV levels were evaluated with GCS and RTS values. The
      control group was constituted of 100 healthy adults. Mean initial MPV value of
      GCS 15-13 patients was 8.25 fL, 8.25 fL in GCS 12-9 patients and 8.47 fL, in GCS
      8-3 patients. Trauma severity was significantly related with initial MPV (iMPV)
      levels (p<0.05), initial Hb (iHb) levels (p<0.05), initial white blood count
      (iWBC) (p<0.05) and initial platelet (iPlt) levels (p<0.05). Severity of trauma
      was related with control MPV (kMPV) levels (p<0.05), control Hb (kHb) (p<0.05),
      control WBC (kWBC) (p<0.05), control Plt (kPlt) levels (p<0.05). MPV levels
      (p<0.05), Hb levels (p<0.05), WBC levels (p<0.05), Plt levels (p<0.05) were
      significantly different between trauma group and healthy group. IMPV and control
      kMPV levels were not related (p=0.149). But kHb - iHb levels (p<0.05), kWBC -
      iWBC levels (p<0.05), kPlt - iPlt levels (p<0.05), kGCS - iiGCS (p<0.05) were
      related to each other. We found a correlation between iMPV and iWBC levels
      (p<0.05, r=-0.342). Similarly, there was a correlation between severity of trauma
      and iMPV level (p<0.05, r=-0.224). We determined a significant correlation
      between iMPV and iPlt levels (p<0.05, r=-0.246). There was not a correlation
      between kMPV and kWBC (p>0.05, r=0.124). kMPV and kPlt levels (p<0.05, r=-0.174)
      were correlated. RTS was statistically related with GCS (p<0.05). Similarly, RTS
      was related with iMPV (p<0.05), iWBC(p<0.05) and iPlt (p<0.05) values, but there
      was not a relation with iHb (p>0.05). We found correlations between iMPV- trauma
      severity (p<0.05, r=-0.224), iMPV - RTS (p<0.05, r=0.134), iMPV - iWBC (p<0.05 r=
      0.342), iMPV - iPlt (p<0.05, r=-0.246). Control RTS (seventh day of
      hospitalization) values were not related to kMPV (p>0.05), kHB (p>0.05), kWBC
      (p>0.05) and kPlt(p>0.05). There was a correlation between kRTS and kMPV (p<0.05,
      r=-0.169). Similarly, kMPV - kHb (p<0.05, r=-0.141), kMPV - kPlt (p<0.05, r=
      0.174) were correlated. KMPV and kPlt were not correlated (p<0.05, r=0.124).
      Initial RTS and seventh day RTS values were significantly different (p<0.05). MPV
      may be helpful for emergency physicians for predicting the severity of trauma.

PMID- 23855432
TI  - Primary Burkitt's lymphoma of endometrium and bilateral ovaries in a 6-year-old
      female: report of a rare entity and review of the published work.
AB  - We report a case of a 6-year-old girl with primary Burkitt's lymphoma (BL) of
      endometrium and bilateral ovaries of 1-month duration. To the best of our
      knowledge, few cases of childhood primary BL of bilateral ovaries have been
      reported worldwide. However, extensive search of the published work did not
      reveal any case of primary BL of endometrium and both ovaries. Although rare, BL
      is a potentially curable malignancy with good prognosis.

PMID- 23855433
TI  - Individual and combined effects of CaCl2 and UV-C on the biosynthesis of
      resveratrols in grape leaves and berry skins.
AB  - The individual and combined effects of calcium chloride (CaCl2) and ultraviolet C
      (UV-C) light on the synthesis of resveratrol in grape leaves and berry skins were
      investigated. Results showed that all treatments could increase leaf resveratrol
      contents at least about 5 times, but the combination treatment was the most
      efficient. Moreover, compared with UV-C treatment, the combination treatment
      delayed the decline of resveratrol contents. The expression levels of
      phenylalanine ammonia lyase (PAL), cinnamate-4-hydroxylase (C4H), coumaroyl-CoA
      ligase (4CL), and stilbene synthase (STS) and 3-O-beta-glycosyltransferases,
      which are related to the synthesis of resveratrol, increased in response to these
      treatments, paralleling the change in resveratrol content. All treatments also
      induced the biosynthesis of resveratrol in berry skins at room temperature. The
      berries of these treatments held at room temperature for 1 day were further
      stored under low temperature (-1 +/- 0.5  degrees C, RH 95%) for 27 days, and the
      results showed that all treatments continuously increased berry skin resveratrol
      content, with the combination treatment being most efficient. During cold
      storage, resveratrol content remained at high levels and reached a maximum (about
      247.7 MUg/g FW) at 13 days, then showed a slight decline, though it remained high
      by the end of storage. Berry firmness and total soluble solids content showed
      slight changes during cold storage, but there were no differences among the
      treatments. Thus, the combination treatment of CaCl2 and UV-C could be an
      efficient method for increasing resveratrol content of table grapes during
      storage under low temperature. This would be potentially beneficial for producing
      functional fruits. 

PMID- 23855434
TI  - Role of cannabinoid CB2 receptor in the reinforcing actions of ethanol.
AB  - This study examines the role of the cannabinoid CB2 receptor (CB2 r) on the
      vulnerability to ethanol consumption. The time-related and dose-response effects
      of ethanol on rectal temperature, handling-induced convulsions (HIC) and blood
      ethanol concentrations were evaluated in CB2 KO and wild-type (WT) mice. The
      reinforcing properties of ethanol were evaluated in conditioned place preference
      (CPP), preference and voluntary ethanol consumption and oral ethanol self
      administration. Water-maintained behavior schedule was performed to evaluate the
      degree of motivation induced by a natural stimulus. Preference for non-alcohol
      tastants assay was performed to evaluate the differences in taste sensitivity.
      Tyrosine hydroxylase (TH) and MU-opioid receptor gene expressions were also
      measured in the ventral tegmental area and nucleus accumbens (NAcc),
      respectively. CB2 KO mice presented increased HIC score, ethanol-CPP, voluntary
      ethanol consumption and preference, acquisition of ethanol self-administration,
      and increased motivation to drink ethanol compared with WT mice. No differences
      were found between genotypes in the water-maintained behavior schedule or
      preference for non-alcohol tastants. Naive CB2 KO mice presented increased MU
      opioid receptor gene expression in NAcc. Acute ethanol administration (1-2 g/kg)
      increased TH and MU-opioid receptor gene expressions in CB2 KO mice, whereas the
      lower dose of ethanol decreased TH gene expression in WT mice. These results
      suggest that deletion of the CB2 r gene increased preference for and
      vulnerability to ethanol consumption, at least in part, by increased ethanol
      induced sensitivity of the TH and MU-opioid receptor gene expressions in
      mesolimbic neurons. Future studies will determine the role of CB2 r as a target
      for the treatment of problems related with alcohol consumption. 

PMID- 23855435
TI  - Screening, brief intervention, and referral to treatment: overview of and student
      satisfaction with an undergraduate addiction training program for nurses.
AB  - Preparing nursing students to apply an evidence-based screening and brief
      intervention approach with patients has the potential to reduce patients' risky
      alcohol and drug use. Responding to Mollica, Hyman, and Mann's article published
      in 2011, the current article describes implementation results of an Addiction
      Training for Nurses program of Screening, Brief Intervention, and Referral to
      Treatment (SBIRT) embedded within an undergraduate nursing curriculum. Results
      reveal that students in other schools of nursing would benefit from similar,
      significant training on substance use disorders and SBIRT. Training satisfaction
      surveys (N = 488) indicate students were satisfied with the quality of the
      training experience. More than 90% of students strongly agreed or agreed that the
      training was relevant to their nursing careers and would help their patients.
      Additional clinical practice and skill development may increase students'
      reported effectiveness in working with the topic area of substance use and SBIRT.

PMID- 23855436
TI  - ECT treatment outcomes following performance improvement changes.
AB  - Differences in electroconvulsive therapy (ECT) outcomes were explored following
      changes in ECT administration at our institution. Two changes were introduced:
      (a) switching the anesthetic agent from propofol to methohexital, and (b) using a
      more aggressive ECT charge dosing regimen for right unilateral (RUL) electrode
      placement. Length of stay (LOS) and number of treatments administered per patient
      were monitored. A retrospective analysis was performed of two inpatient groups
      treated on our Mood Disorders Unit: those who underwent ECT in the 12 months
      prior to the changes (n = 40) and those who underwent treatment in the 12 months
      after the changes (n = 38). Compared with patients receiving ECT with RUL
      placement prior to the changes, patients who received RUL ECT after the changes
      had a significantly shorter inpatient LOS (27.4 versus 18 days, p = 0.028).
      Treatment efficacy monitored by the Montgomery Asberg Depression Rating Scale was
      not impacted. The change in anesthetic agent and charge dosing each accounted for
      11% of the variance in LOS among patients receiving RUL ECT. The implemented
      changes in ECT administration positively impacted outcome for patients receiving
      treatment with RUL electrode placement.

PMID- 23855437
TI  - A qualitative study on the use of the care programme approach with individuals
      with borderline personality disorder: a service user perspective.
AB  - A newly developed specialist personality disorder service in the United Kingdom
      arranged a focus group with seven service users with a diagnosis of borderline
      personality disorder (BPD) to explore their experiences of the Care Programme
      Approach (CPA) while under the care of a community mental health team. A thematic
      analysis generated seven themes. Understanding Borderline Personality Disorder
      and Understanding Recovery were highlighted as difficulties service users face,
      with a lack of staff understanding. They also spoke about the struggle of having
      a voice in their CPA meetings and the lack of information they received in the
      CPA process. They discussed the deliberation between progression versus
      consistency and moving on from services. Service users discussed the challenges
      of accessing treatment and lack of follow up in the CPA process. Greater service
      user involvement in the process would help address the dissatisfaction and
      disempowerment in care planning experienced by individuals diagnosed with BPD.
      [Journal of Psychosocial Nursing and Mental Health Services, 51(10), 38-45.]. 

PMID- 23855438
TI  - Complementary therapy support in cancer survivorship: a survey of complementary
      and alternative medicine practitioners' provision and perception of skills.
AB  - This study reviewed the confidence and perceived skills of complementary and
      alternative medicine (CAM) practitioners in providing care and symptom management
      for clients post cancer. An e-survey was mailed to approximately 21, 000 CAM
      practitioners, targeted at those working with clients who were experiencing
      consequences of cancer and its treatments. Questions were asked about the main
      symptoms and concerns of clients, the confidence and current skill levels of
      practitioners and additional training requirements. Six hundred and twelve
      practitioners responded to the survey, 507 of whom were working with individuals
      experiencing the consequences of cancer and its treatments. Forty-five per cent
      (n = 134) had undertaken training in cancer prior to working with cancer
      patients, 61% (n = 182) had undertaken courses or study days relative to cancer
      care in the past two years. The most often treated symptoms or concerns of
      patients were those of a psychosocial nature, pain management and lymphoedema.
      CAM practitioners with limited knowledge and training are providing support to
      cancer survivors, particularly in services where the National Health Service has
      limited provision. CAM practitioners may fulfil a future role in providing long
      term support for cancer survivors; however, in order to properly safeguard
      patients they are in need of further training and development.

PMID- 23855439
TI  - Effect of alpha lipoic acid on ifosfamide-induced central neurotoxicity in rats.
AB  - Ifosfamide (IFOS) which is a cytotoxic alkylating agent may cause central nervous
      system toxicity. Alpha-lipoic acid (ALA) has a strong antioxidant effects. We
      hypothesized that ALA could attenuate on ifosfamide-induced central neurotoxicity
      in rats. Rats were divided into Control, IFOS, ALA and IFOS+ALA groups. The toxic
      effects of IFOS were analyzed by oxidative parameters and caspase 3
      immunohistochemical examinations of brain tissue. The catalase activity of IFOS
      group significantly reduced in comparison with control groups (p < 0.05). The
      malondialdehyde (MDA) level and protein carbonyl (PC) content in brain tissue
      were significantly higher in IFOS group than in the other groups (p < 0.05). ALA
      treatments significantly prevented the increase in MDA level (p < 0.001) and PC
      content (p < 0.05) in brain tissue. IFOS group showed profound activation of
      caspase 3. The control, ALA and IFOS+ALA groups did not show caspase 3
      activation. It was concluded that ALA treatments may have beneficial effects
      protecting neurons from central neurotoxicity caused by IFOS.

PMID- 23855440
TI  - Straightforward, one-step synthesis of alkanethiol-capped silver nanoparticles
      from an aggregative model of growth.
AB  - Classical nucleation theory and Derjaguin, Landau, Verwey, Overbeek (DLVO) theory
      for colloidal stability were applied to gain insight into the synthesis of
      dodecanethiol (DDT) functionalized silver nanoparticles (NPs) by reduction of
      silver nitrate with sodium borohydride in ethanol. This analysis indicated the
      importance of quickly establishing a dense DDT ligand brush on inherently
      unstable primary particles to achieve colloidal stability. The DLVO calculations
      also indicated that the electrostatic potential was a minor contributor to
      repulsive interactions, signifying that it would be possible to control NP size
      and uniformity in solutions with high ionic strength, as long as sufficient DDT
      was available to form a densely packed ligand layer on the NPs. These insights
      were applied to design a new straightforward, one-step, one-phase synthesis for
      the production of alkanethiol-functionalized silver NPs. To test the insights
      from DLVO theory, 16 samples were synthesized in the parameter space R = 3-12, S
      = 1-12 where R = [NaBH4]/[AgNO3], S = [DDT]/[AgNO3], and [AgNO3] = 10 mM. In
      general, samples with R = 3 or S = 1 were polydisperse; however, samples in the R
      = 6-12 and S = 3-12 range had uniform particle sizes with average diameters
      between 3.5 and 4.7 nm. Additionally, samples with R = 72-108 and S = 12 were
      synthesized to test particle stability at high ionic strength; again, uniform NPs
      with average diameters from 3.5 to 3.8 nm were produced. Ultimately, the insights
      gained from DLVO theory successfully guided the development of a one-step, one
      phase technique for the synthesis of uniform, spherical alkanethiol
      functionalized silver NPs. 

PMID- 23855441
TI  - Anaphylaxis in dogs and cats.
AB  - OBJECTIVE: To review and summarize current information regarding the
      pathophysiology and clinical manifestations associated with anaphylaxis in dogs
      and cats. The etiology, diagnosis, treatment, and prognosis is discussed.
      ETIOLOGY: Anaphylaxis is a systemic, type I hypersensitivity reaction that often
      has fatal consequences. Many of the principal clinical manifestations involve
      organs where mast cell concentrations are highest: the skin, the lungs, and the
      gastrointestinal tract. Histamine and other deleterious inflammatory mediators
      promote vascular permeability and smooth muscle contraction; they are readily
      released from sensitized mast cells and basophils challenged with antigen.
      Anaphylaxis may be triggered by a variety of antigens including insect and
      reptile venom, a variety of drugs, vaccines, and food. DIAGNOSIS: Anaphylaxis is
      a clinical diagnosis made from a collection of signs and symptoms. It is most
      commonly based on pattern recognition. Differential diagnoses include severe
      asthma, pheocromocytoma, and mastocytosis. THERAPY: Epinephrine is considered the
      drug of choice for the treatment of anaphylaxis. It acts primarily as a
      vasopressor in improving hemodynamic recovery. Adjunctive treatments include
      fluid therapy, H1 and H2 antihistamines, corticosteroids, and bronchodilators;
      however, these do not substitute for epinephrine. PROGNOSIS: Prognosis depends on
      the severity of the clinical signs. The clinical signs will vary among species
      and route of exposure. The most severe clinical reactions are associated when the
      antigen is administered parenterally.

PMID- 23855443
TI  - Narrative retelling in children with neurodevelopmental disorders: is there a
      role for nonverbal temporal-sequencing skills?
AB  - Oral narrative retelling is often problematic for children with communicative and
      neurodevelopmental disorders. However, beyond a suggested role of language level,
      little is known about the basis of narrative performance. In this study we
      examine whether oral narrative retelling might be associated not just with
      language level but also with skills related to nonverbal narrative temporal
      sequencing. A diagnostically heterogeneous sample of Swedish-speaking children
      with a full scale IQ >70 was included in the study (N = 55; age 6-9 years).
      Narrative retelling skills were measured using the three subscores from the bus
      story test (BST). Independent predictors included (1) temporal sequencing skills
      according to a picture arrangement test and (2) a language skills factor
      consisting of definitional vocabulary and receptive grammar. Regression analyses
      show that language skills predicted BST Sentence Length and Subordinate Clauses
      subscores, while both temporal sequencing and language were independently linked
      with the BST Information subscore. When subdividing the sample based on nonverbal
      temporal sequencing level, a significant subgroup difference was found only for
      BST Information. Finally, a principal component analysis shows that temporal
      sequencing and BST Information loaded on a common factor, separately from the
      language measures. It is concluded that language level is an important correlate
      of narrative performance more generally in this diagnostically heterogeneous
      sample, and that nonverbal temporal sequencing functions are important especially
      for conveying story information. Theoretical and clinical implications are
      discussed.

PMID- 23855442
TI  - Hydrocephalus is a rare outcome in community-acquired bacterial meningitis in
      adults: a retrospective analysis.
AB  - BACKGROUND: Community-acquired bacterial meningitis (CABM) continues to have a
      high mortality rate and often results in severe sequelae among survivors. Lately,
      an increased effort has been focused on describing the neurological complications
      of meningitis including hydrocephalus. To aid in this field of research we set
      out to ascertain the risk and outcome of hydrocephalus in patients with community
      acquired bacterial meningitis (CABM) in North Denmark Region. METHODS: We
      conducted a retrospective population-based cohort study of CABM cases above 14
      years of age. Cases diagnosed during a 13-year period, 1998 through 2010, were
      identified in a laboratory register and data were acquired through patient
      records. Cases not confirmed by culture met other strict inclusion criteria. The
      diagnosis of hydrocephalus relied upon the radiologists' reports on cranial
      imaging. Outcome was graded according to the Glasgow Outcome Scale at discharge
      from the primary admission. Long-term sequelae were based upon any subsequent
      hospital contacts until the end of 2011. RESULTS: Hydrocephalus was diagnosed in
      five of 165 episodes (3%) and all were classified as communicating. Only 120
      patients had cranial imaging done and in this group the rate was 4.2%. In three
      cases hydrocephalus was present at admission, while two cases were diagnosed on
      days 44 and 99, respectively, due to altered mental status. The aetiology was
      either Eschericia coli (n = 2) or Streptococcus pneumoniae (n = 3). Case fatality
      was 60% among cases with hydrocephalus and 17% among other cases. Case fatality
      was similar irrespective of whether patients had a cranial CT or not.
      CONCLUSIONS: Hydrocephalus was diagnosed in 3% of adolescent and adult cases with
      CABM and had a high case fatality rate in spite of specialised medical care and
      neurosurgical interventions. Our findings are comparable with a recent Dutch
      national prospective study.

PMID- 23855444
TI  - Salivary alpha-amylase as a biomarker for the osmopressor response in healthy
      adults.
AB  - Water ingestion induces a sympathetically mediated increase in blood pressure in
      dysautonomic patients and the elderly, but not consistently in young healthy
      subjects. The aim of study was to determine the extent of the pressor response
      and changes of sympathetic activity biomarker salivary alpha-amylase (sAA) after
      water ingestion in young healthy subjects. Compared with ingestion of 50 mL of
      water, the blood pressure, total peripheral resistance and sAA significantly
      increased and the plasma osmolality decreased 25 min after drinking 500 mL of
      water. The results confirm the osmopressor response in young subjects and suggest
      that sAA may be used as a non-invasive marker of sympathetic activity in future
      studies.

PMID- 23855445
TI  - Impact of vehicle development and fuel quality on exhaust nanoparticle emissions
      of traffic.

PMID- 23855446
TI  - Reduction of lectin valency drastically changes glycolipid dynamics in membranes
      but not surface avidity.
AB  - Multivalency is proposed to play a role in the strong avidity of lectins for
      glycosylated cell surfaces and also in their ability to affect membrane dynamics
      by clustering glycosphingolipids. Lectins with modified valency were designed
      from the beta-propeller fold of Ralstonia solanacearum lectin (RSL) that presents
      six fucose binding sites. After identification of key amino acids by molecular
      dynamics calculations, two mutants with reduced valency were produced. Isothermal
      titration calorimetry confirmed the loss of three high affinity binding sites for
      both mutants. Crystal structures indicated that residual low affinity binding
      occurred in W76A but not in R17A. The trivalent R17A mutant presented unchanged
      avidity toward fucosylated surfaces, when compared to hexavalent RSL. However,
      R17A is not able anymore to induce formation of membrane invaginations on giant
      unilamellar vesicules, indicating the crucial role of number of binding sites for
      clustering of glycolipids. In the human lung epithelial cell line H1299, wt-RSL
      is internalized within seconds whereas the kinetics of R17A uptake is largely
      delayed. Neolectins with tailored valency are promising tools to study membrane
      dynamics. 

PMID- 23855447
TI  - Protection of montelukast on OVA-induced eosinophilic gastroenteritis via
      modulating IL-5, eotaxin-1 and MBP expression.
AB  - The aim of this study was to further explore the possible mechanisms of
      montelukast on oral mice ovalbumin-induced eosinophilic gastroenteritis in a
      mouse model. The results indicated that montelukast could prevent levels of
      eotaxin-1 and interleukin-5 in intestinal mucosa homogenate when compared with
      model group. Interestingly, the increase of major basic protein expression in
      jejunal tissue also was attenuated by treated with montelukast.

PMID- 23855448
TI  - Investigating bioconjugation by atomic force microscopy.
AB  - Nanotechnological applications increasingly exploit the selectivity and
      processivity of biological molecules. Integration of biomolecules such as
      proteins or DNA into nano-systems typically requires their conjugation to
      surfaces, for example of carbon-nanotubes or fluorescent quantum dots. The
      bioconjugated nanostructures exploit the unique strengths of both their
      biological and nanoparticle components and are used in diverse, future oriented
      research areas ranging from nanoelectronics to biosensing and nanomedicine.
      Atomic force microscopy imaging provides valuable, direct insight for the
      evaluation of different conjugation approaches at the level of the individual
      molecules. Recent technical advances have enabled high speed imaging by AFM
      supporting time resolutions sufficient to follow conformational changes of
      intricately assembled nanostructures in solution. In addition, integration of AFM
      with different spectroscopic and imaging approaches provides an enhanced level of
      information on the investigated sample. Furthermore, the AFM itself can serve as
      an active tool for the assembly of nanostructures based on bioconjugation. AFM is
      hence a major workhorse in nanotechnology; it is a powerful tool for the
      structural investigation of bioconjugation and bioconjugation-induced effects as
      well as the simultaneous active assembly and analysis of bioconjugation-based
      nanostructures. 

PMID- 23855449
TI  - Health promotion in individuals with mental disorders: a cluster preference
      randomized controlled trial.
AB  - BACKGROUND: The existing literature on weight management interventions targeting
      physical activity and healthy eating in mental health care appears to provide
      only limited evidence. The aim of the study was to examine the effectiveness of a
      10-week health promotion intervention, followed by a 6-month follow-up period in
      individuals with mental disorders living in sheltered housing in the Flanders
      region (Belgium). METHODS: The study had a cluster preference randomized
      controlled design. Twenty-five sheltered housing organisations agreed to
      participate (16 in the intervention group, nine in the control group). In the
      intervention group, 225 individuals agreed to participate, while in the control
      group 99 individuals entered into the study. The main outcomes were changes in
      body weight, Body Mass Index, waist circumference and fat mass. Secondary
      outcomes consisted of changes in physical activity levels, eating habits, health
      related quality of life and psychiatric symptom severity. RESULTS: A significant
      difference was found between the intervention group and the control group
      regarding body weight (-0.35 vs. +0.22 kg; p=0.04), Body Mass Index (-0.12 vs.
      +0.08 kg/m2; p=0.04), waist circumference (-0.29 vs. + 0.55 cm; p<0.01), and fat
      mass (-0.99 vs. -0.12%; p<0.01). The decrease in these outcomes in the
      intervention group disappeared during the follow up period, except for fat mass.
      Within the intervention group, a larger decrease in the primary outcomes was
      found in the participants who completed the intervention. No significant
      differences between the two groups in changes in the secondary outcomes were
      found, except for the pedometer-determined steps/day. In the intervention group,
      the mean number of daily steps increased, while it decreased in the control
      group. CONCLUSIONS: The study demonstrated that small significant improvements in
      the primary outcomes are possible in individuals with mental disorders.
      Integration of health promotion activities targeting physical activity and
      healthy eating into daily care are, however, necessary to maintain the promising
      results. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov NCT
      01336946.

PMID- 23855450
TI  - The European TREatment of severe Atopic eczema in children Taskforce (TREAT)
      survey.
AB  - BACKGROUND: There is a paucity of evidence for the use of systemic agents in
      children with atopic eczema refractory to conventional therapy, resulting in
      considerable variation in patient management. OBJECTIVES: The European TREatment
      of severe Atopic eczema in children Taskforce (TREAT) survey was established to
      collect data on current prescribing practice, to identify factors influencing the
      use of specific systemic agents, and to inform the design of a clinically
      relevant intervention study. METHODS: Consultant physician members of the
      paediatric dermatology societies and interest groups of eight European countries
      were invited to participate in a web-based survey. The multiple-response format
      questionnaire collated data on clinical practice in general, as well as detailed
      information on the use of systemic agents in refractory paediatric atopic eczema.
      RESULTS: In total, 343/765 members (44.8%) responded to the invitational emails;
      89.2% were dermatologists and 71% initiate systemic immunosuppression for
      children with severe atopic eczema. The first-line drugs of choice were
      ciclosporin (43.0%), oral corticosteroids (30.7%) and azathioprine (21.7%).
      Ciclosporin was also the most commonly used second-line medication (33.6%), with
      methotrexate ranked as most popular third choice (26.2%). Around half of the
      respondents (53.7%) replied that they routinely test and treat reservoirs of
      cutaneous infection prior to starting systemic treatment. Across the eight
      countries, penicillins were the first-line antibiotic of choice (78.3%).
      CONCLUSIONS: In the absence of a clear evidence base, the European TREAT survey
      confirms the wide variation in prescribing practice of systemic immunosuppression
      in refractory paediatric atopic eczema. The results will be used to inform the
      design of a randomized controlled trial relevant to patient management across
      Europe.

PMID- 23855451
TI  - Causal responsibility and counterfactuals.
AB  - How do people attribute responsibility in situations where the contributions of
      multiple agents combine to produce a joint outcome? The prevalence of over
      determination in such cases makes this a difficult problem for counterfactual
      theories of causal responsibility. In this article, we explore a general
      framework for assigning responsibility in multiple agent contexts. We draw on the
      structural model account of actual causation (e.g., Halpern & Pearl, 2005) and
      its extension to responsibility judgments (Chockler & Halpern, 2004). We review
      the main theoretical and empirical issues that arise from this literature and
      propose a novel model of intuitive judgments of responsibility. This model is a
      function of both pivotality (whether an agent made a difference to the outcome)
      and criticality (how important the agent is perceived to be for the outcome,
      before any actions are taken). The model explains empirical results from previous
      studies and is supported by a new experiment that manipulates both pivotality and
      criticality. We also discuss possible extensions of this model to deal with a
      broader range of causal situations. Overall, our approach emphasizes the close
      interrelations between causality, counterfactuals, and responsibility
      attributions. 

PMID- 23855453
TI  - A more comprehensive overview of executive dysfunction in children with cerebral
      palsy: theoretical perspectives and clinical implications.

PMID- 23855452
TI  - Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic
      adenocarcinoma cells to gemcitabine.
AB  - Checkpoint kinase 2 (CHK2) plays pivotal function as an effector of cell cycle
      checkpoint arrest following DNA damage. Recently, we found that co-treatment of
      NSC109555 (a potent and selective CHK2 inhibitor) potentiated the cytotoxic
      effect of gemcitabine (GEM) in pancreatic cancer MIA PaCa-2 cells. Here, we
      further examined whether NSC109555 could enhance the antitumour effect of GEM in
      pancreatic adenocarcinoma cell lines. In this study, the combination treatment of
      NSC109555 plus GEM demonstrated strong synergistic antitumour effect in four
      pancreatic cancer cells (MIA PaCa-2, CFPAC-1, Panc-1 and BxPC-3). In addition,
      the GEM/NSC109555 combination significantly increased the level of intracellular
      reactive oxygen species (ROS), accompanied by induction of apoptotic cell death.
      Inhibition of ROS generation by N-acetyl cysteine (NAC) significantly reversed
      the effect of GEM/NSC109555 in apoptosis and cytotoxicity. Furthermore, genetic
      knockdown of CHK2 by siRNA enhanced GEM-induced apoptotic cell death. These
      findings suggest that inhibition of CHK2 would be a beneficial therapeutic
      approach for pancreatic cancer therapy in clinical treatment. 

PMID- 23855454
TI  - Double-balloon enteroscopy in the diagnosis of suspected isolated Crohn's disease
      of the small bowel.
AB  - BACKGROUND AND AIM: Diagnosis of Crohn's disease (CD) with isolated involvement
      of the small bowel remains a major challenge. Diagnostic procedures allowing
      direct insight into the midgut have become available with the introduction of
      double-balloon enteroscopy (DBE) and video-capsule endoscopy (VCE). The aim of
      the present study was to evaluate the role of DBE in the diagnosis of isolated CD
      of the small bowel. METHODS: Sixteen patients (seven males) with suspected CD of
      the small bowel after exclusion of abnormal changes in the upper gastrointestinal
      tract and colon by esophagogastroduodenoscopy and colonoscopy including histology
      underwent DBE and high-resolution transabdominal ultrasound. RESULTS: In seven of
      16 (44%) patients, abnormal macroscopic findings were detected by DBE (e.g.
      ileitis terminalis, inflammatory stenosis, aphthous lesions or jejunal ulcers).
      In one of thecases, histology confirmed pathognomonic findings consistent with
      CD. However, the diagnosis of CD was confirmed in 11/16 (69%) patients taking
      into account the clinical presentation and course of the disease as well as the
      endoscopic and imaging results. CONCLUSIONS: In cases of CD with clinical
      expression limited to the small bowel, DBE is a helpful tool. Nevertheless, in
      these patients, the combination of clinical findings and additional imaging
      modalities is required for confirmation of the diagnosis. A suggestive medical
      history, high-resolution ultrasound, EGD and colonoscopy lead the algorithm
      before the assessment with DBE.

PMID- 23855455
TI  - Monoarticular carcinomatous knee joint arthritis as an initial presentation of
      cervical carcinoma.
AB  - When it comes to cancer, one can expect the unexpected. The clinical
      presentations can be very bizarre. One of these uncommon presentations is
      monoarticular arthritis. The age group affected by cancer and arthritis are
      similar. However, the possibility of joint pain being secondary to metastatic
      involvement does not come to mind easily. In this report, a 65-year-old
      postmenopausal woman presented with complaint of pain and restricted movement of
      the right knee joint, in whom the clinical and magnetic resonance imaging
      features were suggestive of infective monoarthritis. However, synovial fluid
      aspirate showed presence of malignant cells. Hence, patient was evaluated with
      whole-body (18)F-fluorodeoxyglucose positron emission tomography computed
      tomography which detected primary malignancy of the cervix with regional nodal
      and right knee joint metastasis. To our knowledge, this is the first reported
      case of cervical malignancy with solitary skeletal metastasis involving the knee
      joint. The report also discusses overall incidence of malignant arthritis.

PMID- 23855456
TI  - Intravenous administration of desmopressin acetate to reverse acetylsalicylic
      acid-induced coagulopathy in three dogs.
AB  - BACKGROUND: Acetylsalicylic acid (ie, aspirin) administration inhibits platelet
      aggregation in dogs and is associated with increased perioperative blood loss and
      transfusion requirements in people. Desmopressin acetate (DDAVP) is used to
      control or prevent bleeding in dogs with type 1 von Willebrand disease and is
      also widely reported in the human literature as an emergency antithrombotic
      reversal agent. KEY FINDINGS: Three dogs undergoing surgery for intervertebral
      disc disease had marked prolongations in buccal mucosal bleeding time (BMBT)
      after aspirin administration. DDAVP was given intravenously preoperatively and
      achieved prompt reversal of the prolongation in BMBT. None of the dogs
      experienced intraoperative bleeding complications. SIGNIFICANCE: IV DDAVP
      corrected prolongations in BMBT in dogs given aspirin and should be considered in
      dogs requiring prompt reversal of aspirin-induced coagulopathies to reduce the
      risk of bleeding complications.

PMID- 23855457
TI  - A survey of female students with migraine: what is the influence of family
      history and lifestyle?
AB  - OBJECTIVES: To compare characteristics of migraine and some lifestyle habits in
      migraineurs with and without a positive family history for migraine. METHOD: The
      prevalence study was combined with a case-control study and comprised 245 female
      students with migraine. RESULTS: Out of 245 female students with migraine, 132
      (53.9%) had a positive family history for migraine. In comparison with
      migraineurs who had not, those with a positive family history were younger at the
      onset of migraine and significantly more frequently reported menstrual migraine
      (p < 0.001), unilateral pain (p < 0.05) and pulsate pain (p < 0.05) as well as
      severe headache (p < 0.01). In comparison to migraineurs with a positive family
      history for migraine, those who did not report a significantly higher frequency
      of average number of meals per day of <3 (p < 0.001), missed meals (p < 0.05) and
      an average sleep duration of <= 6 h (p < 0.05). CONCLUSIONS: The results of the
      present study are in line with literature showing a high frequency of positive
      family history for migraine among migraineurs. They also suggest that subjects
      with a positive family history have a lower "migrainous threshold" for the
      development of migraine and that environmental factors are more important for the
      occurrence of migraine in subjects without a positive family history.
      Accordingly, the conclusions of this study are limited to reproductive aged
      women.

PMID- 23855458
TI  - Principal component structuring of the non-REM Sleep EEG spectrum in older adults
      yields age-related changes in the sleep and wake drives.
AB  - Age-related disturbances of the sleep-wake cycle can reflect ontogenetic changes
      in regulatory mechanisms underlying normal and pathological aging, but the exact
      nature of these changes remains unclear. The present report is the first attempt
      to apply principal component analysis to the electroencephalographic (EEG)
      spectrum to examine of whether the observed age-related changes in the objective
      sleep measures can be linked to the opponent sleep-promoting and wake-promoting
      processes. The EEG indicators of these processes--scores on the 1st and 2nd
      principal components of the EEG spectrum, respectively--were compared in 15 older
      (57-74 years) and 16 younger (20-31 years) healthy volunteers. The scores were
      calculated for non-REM sleep episodes which occurred during ten 75-min naps
      scheduled every 150 min throughout a 40-h constant routine protocol. Both, a
      decrease of the 1st principal component score and an increase of the 2nd
      principal component score were found to contribute to such most obvious age
      related modification of the sleep EEG spectrum as attenuation of EEG slow-wave
      activity in older people. Therefore, we concluded that the normal aging process
      can reflect both a weakening of the sleep-promoting process and a strengthening
      of the wake-promoting process, respectively. Such bidirectional changes in
      chronoregulatory processes may explain why sleep of older people is characterized
      by the few profitable and a number of detrimental features (i.e., a better
      ability to cope with daytime sleepiness and sleep loss vs. difficulty of falling
      asleep, decreased total nighttime sleep, "lightened" and fragmentized sleep,
      unwanted early morning awakenings, etc.).

PMID- 23855459
TI  - Renewal effects in interference between outcomes as measured by a cued response
      reaction time task: further evidence for associative retrieval models.
AB  - Two experiments demonstrated renewal effects in interference between outcomes in
      human participants. Experiment 1 revealed a XYX renewal effect, whereas
      Experiment 2 showed a XYZ renewal effect. The results from both experiments
      conformed to Bouton's (1993) theory of interference and recovery from
      interference, and contradicted the predictions derived from alternative accounts.
      Unlike previous demonstration of renewal effects, a cued response reaction time
      (RT) task was used, able to detect the effects of fast retrieval processes based
      on associative activation and that allowed little impact of inferential
      reasoning.

PMID- 23855460
TI  - What is new for resveratrol? Is a new set of recommendations necessary?
AB  - Numerous scientific papers have suggested health-promoting effects of
      resveratrol, including claims in the prevention of diseases such as coronary
      heart disease, diabetes, and cancer. Therefore, it was proposed that the
      scientific community needed to express recommendations on the human use of
      resveratrol. Such recommendations were formulated after the first international
      resveratrol conference in Denmark, Resveratrol2010. The working group stated that
      the evidence was "not sufficiently strong to justify recommendation for the
      chronic administration of resveratrol to human beings, beyond the dose which can
      be obtained from dietary sources." It was a disappointing conclusion relative to
      the positive claims about the therapeutic potential of resveratrol made by the
      media. However, since 2010, results from the first clinical trials on resveratrol
      have been made available. Because of these emerging results, it is necessary to
      formulate updated versions of the recommendations. 

PMID- 23855461
TI  - Resveratrol in the management of human cancer: how strong is the clinical
      evidence?
AB  - Among the plethora of biochemical mechanisms engaged by resveratrol in
      preclinical systems, its anticarcinogenic effects represent some of the most
      convincing and intriguing. As outlined in this review, there is considerable
      interest in developing resveratrol for cancer prevention and treatment. The
      plasma pharmacokinetics of resveratrol in humans are now reasonably well defined,
      and studies have shown that repeated daily doses up to 1 g are safe and well
      tolerated, although gastrointestinal toxicity is observed at higher intakes.
      However, care is needed regarding underlying conditions in specific patient
      groups, and there is potential for drug interactions at doses greater than 1
      gram. Little is known regarding the pharmacodynamic effects of resveratrol in
      humans, but the observation that it modulates components of the insulin-like
      growth factor system in the plasma of volunteers is encouraging. While the
      knowledge base that helps determine whether resveratrol may be useful in cancer
      management has increased substantially in recent years, important questions
      remain.

PMID- 23855462
TI  - Resveratrol analogs: promising chemopreventive agents.
AB  - Although resveratrol can modulate multiple stages of carcinogenesis, by most
      common standards it is not a good drug candidate. Resveratrol lacks potency, high
      efficacy, and target specificity; it is rapidly metabolized and serum
      concentrations are low. Using resveratrol as a scaffold, we produced over 100
      derivatives, some of which have target specificity in the nanomolar range.
      Aromatase inhibition was enhanced over 6000-fold by using 1,3-thiazole as the
      central ring of resveratrol. Optimizing the substitution pattern of the two
      phenyl rings and the central heterocyclic linker led to selective QR1 induction
      with a CD value of 87 nM. Several derivatives have been selected for evaluation
      of synergistic effects. Preliminary results with pairs of compounds are promising
      and further experiments, in a constant multidrug manner, will allow us to create
      polygonograms for larger combinations of derivatives. The objective is to develop
      a highly efficacious cocktail of derivatives based on the structure of
      resveratrol.

PMID- 23855463
TI  - Resveratrol and its metabolites modulate cytokine-mediated induction of eotaxin-1
      in human pulmonary artery endothelial cells.
AB  - Coronary heart disease (CHD) is a leading cause of death in many developed
      countries. Evidence has long implicated endothelial injury and inflammation as
      apical events in the pathogenesis of atherosclerosis, the primary cause of CHD.
      Numerous risk factors contribute to a damaged, inflamed endothelium. Conversely,
      cardioprotective agents targeting the dysfunctional endothelium have also been
      identified, notably from dietary sources. We have used cultured human pulmonary
      artery endothelial cells (HPAECs) to test the diet-mediated cardioprotective
      hypothesis. In this review, we summarize our recent findings on control of
      transcription and expression of inflammation biomarker eotaxin-1 in HPAECs
      exposed to single or combined proinflammatory cytokines interleukin-13 (IL-13)
      and tumor necrosis factor-alpha (TNF-alpha), and attenuation of the observed
      eotaxin-1 responses by prior or simultaneous treatment with resveratrol and its
      metabolites. Control of eotaxin-1 gene regulation may be considered an in vitro
      model to evaluate agents linking cardioprotection with endothelial cell damage
      and inflammation. 

PMID- 23855464
TI  - Resveratrol in primary and secondary prevention of cardiovascular disease: a
      dietary and clinical perspective.
AB  - Primary prevention of cardiovascular disease (CVD) aims to avoid a first event in
      subjects that are at risk but have not yet been diagnosed with heart disease.
      Secondary prevention of CVD aims to avoid new events in patients with established
      heart disease. Both approaches involve clinical intervention and implementation
      of healthy lifestyles. The grape and wine polyphenol resveratrol (3,5,4'
      trihydroxy-trans-stilbene) has shown cardioprotective benefits in humans. Most of
      these approaches deal with rather high doses and short follow-ups, and do not
      address the issue of long-term resveratrol consumption safety, especially in
      medicated individuals. Here, we review the trials conducted with resveratrol in
      patients at risk for or with established CVD, focusing on the two longest human
      clinical trials reported so far (1-year follow-up). We also discuss the
      expectations for resveratrol from a dietary and clinical perspective in relation
      to CVD. However, statistically significant changes in CVD-risk markers do not
      necessarily equal clinical significance in the daily care of patients. 

PMID- 23855465
TI  - Evidence for circulatory benefits of resveratrol in humans.
AB  - Impairments of endothelial function, which can be assessed noninvasively by flow
      mediated dilation (FMD) of the brachial artery, contribute to the development of
      cardiovascular disease. Associations between FMD and cognition suggest a vascular
      component in the loss of cognitive function. Certain vasoactive nutrients that
      have been shown to improve FMD may also have the potential to enhance cerebral
      perfusion and cognition. Preclinical studies show that trans-resveratrol can
      enhance nitric oxide bioavailability, thereby increasing endothelium-dependent
      vasodilation. We have now shown that acute administration of resveratrol elicits
      dose-dependent increases of FMD with greater potency than other vasoactive
      nutrients and that this benefit is sustained following regular consumption. We
      describe the potential implications of this vasodilator benefit of resveratrol
      and its role in enhancing cerebrovascular and cognitive functions. 

PMID- 23855466
TI  - Osteogenic effects of resveratrol in vitro: potential for the prevention and
      treatment of osteoporosis.
AB  - There are a number of pharmacological agents for the treatment of bone mineral
      loss and osteoporosis. Hormone replacement therapy (HRT) with estrogen is an
      established treatment, but it has several adverse side effects and can increase
      the risk of cancer, heart disease, and stroke. There is increasing interest in
      nutritional factors and naturally occurring phytochemical compounds with the
      potential for preventing age-related and postmenopausal bone loss. Resveratrol
      (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic phytoestrogen with
      osteogenic and osteoinductive properties. It can modify the metabolism of bone
      cells and has the capacity to modulate bone turnover. This paper provides an
      overview of current research on resveratrol and its effects on bone cells in
      vitro, highlighting the challenges and opportunities facing this area of
      research, especially in the context of providing nutritional support for
      postmenopausal women who may not benefit from HRT and older patients with various
      forms of arthritis, metabolic bone disease, and osteoporosis. 

PMID- 23855467
TI  - Resveratrol in mammals: effects on aging biomarkers, age-related diseases, and
      life span.
AB  - Through its antioxidant, anticarcinogenic, and anti-inflammatory properties,
      resveratrol has become a candidate for drug development in the context of aging
      studies. Scientific evidence has highlighted its potential as a therapeutic agent
      for cardiovascular diseases and some cancers but also as an antiaging molecule.
      Resveratrol is thought to mimic the beneficial effects of chronic and moderate
      calorie restriction. Nevertheless, no study has demonstrated the prolongation of
      life span in healthy nonobese mammal models. This review summarizes recent
      findings on the effects of resveratrol on aging and life span in mammals. In our
      opinion, more studies should be performed to assess the effects of a chronic
      dietary intake of resveratrol in long-lived species close to humans, such as
      nonhuman primates. This will certainly generate more evidence about the ability
      of resveratrol to achieve the physiological benefits that have been observed in
      small mammal laboratory models and feature the eventual unwanted secondary
      effects that may occur under high levels of resveratrol. 

PMID- 23855468
TI  - Resveratrol in metabolic health: an overview of the current evidence and
      perspectives.
AB  - In the search for novel preventive and therapeutic modalities in the management
      of metabolic diseases and obesity, resveratrol has attracted great attention over
      the past decades. Preclinical trials suggest that resveratrol mimics the
      metabolic effects of calorie restriction (CR) via activation of silent mating
      type information regulation 2 homolog 1 (SIRT1). In experimental animals, this
      potential translates into prevention or improvement of glucose metabolism, anti
      inflammation, cancer, and nonalcoholic fatty liver disease. Moreover, and in
      accordance with CR, supplementation with resveratrol promotes longevity in
      several primitive species and protects against diet-induced metabolic
      abnormalities in rodents. Despite the substantial preclinical evidence, human
      clinical data are very scarce, and even though the compound is widely distributed
      as an over-the-counter human nutritional supplement, its therapeutic rationale
      has not been well characterized. In this review, we provide a brief overview of
      the field and discuss the future scientific directions of resveratrol research. 

PMID- 23855469
TI  - Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues
      for health benefits?
AB  - The number of people suffering from metabolic disorders is dramatically
      increasing worldwide. The need for new therapeutic strategies to combat this
      growing epidemic of metabolic diseases is therefore also increasing. In 2003,
      resveratrol was discovered to be a small molecule activator of sirtuin 1 (SIRT1),
      an important molecular target regulating cellular energy metabolism and
      mitochondrial homeostasis. Rodent studies have clearly demonstrated the potential
      of resveratrol to improve various metabolic health parameters. To date, however,
      only limited clinical data are available that have systematically examined the
      health benefits of resveratrol in metabolically challenged humans. This short
      review will give an overview of the currently available clinical studies
      examining the effects of resveratrol on obesity and type 2 diabetes from a human
      perspective. 

PMID- 23855470
TI  - Importance of lipid microdomains, rafts, in absorption, delivery, and biological
      effects of resveratrol.
AB  - The preventive effects of the phytoalexin trans-resveratrol toward cancer have
      been largely described at the cellular and molecular levels in both in vivo and
      in vitro models; however, its primary targets are still poorly identified. In
      this review, we show the crucial role of cell membrane microdomains, that is,
      lipid rafts, not solely in the initiation of the early biochemical events
      triggered by resveratrol leading to cancer cell death, but also in resveratrol
      absorption and distribution. Resveratrol accumulates in lipid rafts and is then
      taken up by cells through raft-dependent endocytosis. These events allow early
      activation of kinase pathways and redistribution of cell death receptors within
      lipid microdomains, events ultimately leading to apoptotic cell death. 

PMID- 23855471
TI  - Interplay between metabolism and transport of resveratrol.
AB  - Resveratrol exhibits a variety of biological and pharmacological activities
      despite its extensive metabolism to sulfates and glucuronides in the intestine
      and liver. The metabolism of resveratrol is cell specific and strongly correlates
      with enzyme expression levels. However, a high rate of biotransformation, in
      concert with the action of the efflux transporters MRP2, MRP3, and ABCG2, reduces
      intracellular resveratrol concentrations, and may thereby decrease its
      pharmacological activity. Interestingly, biotransformation is also dependent on
      disease status. For example, significantly greater sulfation of resveratrol
      occurs in human breast tumor tissue than in adjacent nonmalignant tissue. The
      observed differences, however, do not correlate with the expression of
      sulfotransferases responsible for catalyzing resveratrol sulfation, but rather
      with significantly higher steroid sulfatase mRNA levels. The in vitro activity of
      resveratrol sulfates may not necessarily reflect their in vivo function, given
      the fact that ubiquitously existing human sulfatases can convert the metabolites
      back to active resveratrol in humans. 

PMID- 23855472
TI  - Nano- and micro-encapsulated systems for enhancing the delivery of resveratrol.
AB  - There has been interest in the use of trans-resveratrol as a natural preventative
      agent for improving health and alleviating a range of diseases. However,
      resveratrol has low bioavailability, and this has been associated with its poor
      water solubility, its low stability against environmental stress, and its
      inability to reach a target site in the body to exert the desired health effect.
      Encapsulation offers a potential approach for enhancing the solubility of
      resveratrol, stabilizing it against trans-to-cis isomerization, and improving its
      bioavailability. A range of encapsulant materials, formulations, and technologies
      have been examined for enhancing the delivery of resveratrol. Research on the
      efficacy of encapsulated resveratrol formulations and relevant doses for specific
      applications is required before recommendations may be made for the use of these
      formulations for human health outcomes. 

PMID- 23855474
TI  - An adipocentric perspective of resveratrol as a calorie restriction mimetic.
AB  - Adipose tissue is an active endocrine organ that responds to changes in energy
      balance and influences whole-body physiology. Adipose tissue dysfunction with
      obesity is associated with metabolic disease, neurodegeneration, inflammation,
      and cancer, whereas calorie restriction (CR) decreases both adiposity and disease
      risk. Although resveratrol does not affect obesity, it mimics long-term CR by
      increasing both life span in model organisms and health span in rodents. Because
      resveratrol's benefits in experimental animals are reminiscent of improved
      adipose tissue function under CR, this review synthesizes existing data to assess
      if resveratrol's effects may be mediated by mimicking CR in adipose tissue. In
      metabolically unhealthy humans, resveratrol consumption recapitulates the health
      benefits of CR, whereas short-term resveratrol in otherwise healthy humans mimics
      CR at the transcriptional, but not physiological, level. This latter observation
      (neutral effect of short-term resveratrol) may be protective against future
      disease risk; however, long-term studies in healthy humans will be needed to
      support this hypothesis. 

PMID- 23855473
TI  - Resveratrol-based combinatorial strategies for cancer management.
AB  - In recent years combination chemoprevention has been increasingly appreciated and
      investigated as a viable and effective strategy for cancer management. A plethora
      of evidence suggests that a combination of agents may afford synergistic (or
      additive) advantage for cancer management by multiple means, such as by (1)
      enhancing the bio-availability of chemopreventive agents, (2) modifying different
      molecular targets, and (3) lowering the effective dose of agent/drug to be used
      for cancer management. Resveratrol has been shown to afford chemopreventive and
      therapeutic effects against certain cancers. Recent studies are suggesting that
      resveratrol may be very useful when given in combination with other agents. The
      two major advantages of using resveratrol in combination with other agents are
      synergistically or additively enhancing the efficacy against cancer and limiting
      the toxicity and side effects of existing therapies. However, concerted and
      multidisciplinary efforts are needed to identify the most optimal combinatorial
      strategies. 

PMID- 23855475
TI  - The pig as a valuable model for testing the effect of resveratrol to prevent
      cardiovascular disease.
AB  - Resveratrol is a naturally occurring polyphenol found in the skin of red grapes,
      peanuts, and red wine that has been shown to modify many cardiovascular risk
      factors. Small animal models have been extensively used to investigate
      cardiovascular disease, but the results often fail to translate in clinical
      trials. Disease-specific pig models are emerging as clinically useful tools that
      may offer insight into cardiovascular disease and the effect of drugs such as
      resveratrol on cardiovascular health. In this paper, we discuss the advantage of
      using clinically relevant pig models of diabetes, hypercholesterolemia, and
      myocardial ischemia to investigate the role of resveratrol in cardiovascular
      disease prevention. 

PMID- 23855476
TI  - Resveratrol, from experimental data to nutritional evidence: the emergence of a
      new food ingredient.
AB  - The polyphenol resveratrol is found notably in grapes and in a variety of
      medicinal plants. Recently, resveratrol has been suggested to have
      cardioprotective effects and to improve metabolic health by mimicking the effects
      of calorie restriction. Numerous animal and in vitro studies suggest that
      resveratrol could improve cardiovascular and metabolic health in humans. In view
      of this compelling preclinical evidence, several human studies investigating the
      effects of resveratrol on vascular and metabolic health have been initiated.
      Collectively, the animal, human epidemiological, and first human intervention
      studies support a role of resveratrol in vascular and metabolic health. This has
      led to the introduction of the first supplement and food products containing
      resveratrol and its emergence as a promising new health ingredient. Thus,
      supplementation with resveratrol may be included in nutritional and lifestyle
      programs aiming to reduce the risk of vascular and obesity-related problems. 

PMID- 23855477
TI  - Meta-analysis: the impact of disease activity at conception on disease activity
      during pregnancy in patients with inflammatory bowel disease.
AB  - BACKGROUND: The rate of exacerbation of inflammatory bowel disease (IBD) during
      pregnancy varies in the published literature. AIM: We sought to perform a
      systematic review and meta-analysis of the effects of disease activity at
      conception on disease course during pregnancy in women with IBD. METHODS:
      Published studies and abstracts from standard sources were screened for
      appropriate studies. Data were pooled and analysed using funnel and forest plots.
      Quality assessment scores were given using GRADE criteria. RESULTS: Fourteen
      studies were eligible for inclusion; ten studies contained patients with UC (N =
      1130), and six studies contained patients with CD (N = 590). In patients with UC
      there was a significantly higher risk ratio of active disease during pregnancy in
      patients who commenced pregnancy with active disease (55%), when compared with
      those in remission at conception (36%) (RR 2.0, 95% CI: 1.5-3, P < 0.001). This
      risk was also higher in patients with CD (RR 2.0, 95% CI: 1.2-3.4, P = 0.006).
      Thirteen of the studies rated 'low' in all domains of a quality assessment, and
      there was significant statistical heterogeneity. CONCLUSIONS: Patients with IBD
      who conceive when their disease is active are more likely to have active disease
      during pregnancy than those who conceive when in remission. All studies used in
      this analysis had a high risk of bias therefore further studies are required.

PMID- 23855479
TI  - Ticagrelor reduces neutrophil recruitment and lung damage in abdominal sepsis.
AB  - Abstract Platelets play an important role in abdominal sepsis and P2Y12 receptor
      antagonists have been reported to exert anti-inflammatory effects. Herein, we
      assessed the impact of platelet inhibition with the P2Y12 receptor antagonist
      ticagrelor on pulmonary neutrophil recruitment and tissue damage in a model of
      abdominal sepsis. Wild-type C57BL/6 mice were subjected to cecal ligation and
      puncture (CLP). Animals were treated with ticagrelor (100 mg/kg) or vehicle prior
      to CLP induction. Edema formation and bronchoalveolar neutrophils as well as lung
      damage were quantified. Flow cytometry was used to determine expression of
      platelet-neutrophil aggregates, neutrophil activation and CD40L expression on
      platelets. CLP-induced pulmonary infiltration of neutrophils at 24 hours was
      reduced by 50% in ticagrelor-treated animals. Moreover, ticagrelor abolished CLP
      provoked lung edema and decreased lung damage score by 41%. Notably, ticagrelor
      completely inhibited formation of platelet-neutrophil aggregates and markedly
      reduced thrombocytopenia in CLP animals. In addition, ticagrelor reduced platelet
      shedding of CD40L in septic mice. Our data indicate that ticagrelor can reduce
      CLP-induced pulmonary neutrophil recruitment and lung damage suggesting a
      potential role for platelet antagonists, such as ticagrelor, in the management of
      patients with abdominal sepsis.

PMID- 23855478
TI  - Avidity modulation of folate-targeted multivalent dendrimers for evaluating
      biophysical models of cancer targeting nanoparticles.
AB  - We investigated two types of generation 5 polyamidoamine (PAMAM) dendrimers, each
      conjugated stochastically with a mean number of 5 or 10 methotrexate (MTX)
      ligands per dendrimer (G5-MTX5, G5-MTX10), for their binding to surface
      immobilized folate binding protein (FBP) as a function of receptor density. The
      binding study was performed under flow by surface plasmon resonance spectroscopy.
      Two multivalent models were examined to simulate binding of the dendrimer to the
      receptor surface, showing that at relatively high receptor density, both
      dendrimer conjugates exhibit high avidity. However, upon reducing the receptor
      density by a factor of 3 and 13 relative to the high density level, the avidity
      of the lower-valent G5-MTX5 decreases by up to several orders of magnitude (KD =
      nM to MUM), whereas the avidity of G5-MTX10 remains largely unaffected regardless
      of the density variation. Notably, on the 13-fold reduced FBP surface, G5-MTX5
      displays binding kinetics similar to that of monovalent methotrexate, which is
      patently different from the still tight binding of the higher-valent G5-MTX10.
      Thus, the binding analysis demonstrates that avidity displayed by multivalent MTX
      conjugates varies in response to the receptor density and can be modulated for
      achieving tighter, more specific binding to the higher receptor density by
      modulation of ligand valency. We believe this study provides experimental
      evidence supportive of the mechanistic hypothesis of multivalent NP uptake to a
      cancer cell over a healthy cell where the diseased cell expresses the folate
      receptor at higher density. 

PMID- 23855480
TI  - Ion trapping for ion mobility spectrometry measurements in a cyclical drift tube.
AB  - A new ion trapping technique, involving the accumulation of ions in a cyclical
      drift tube, as a means of enhancing ion signals for scanning ion cyclotron
      mobility measurements has been modeled by computational simulations and
      demonstrated experimentally. In this approach, multiple packets of ions are
      periodically released from a source region into the on ramp region of the
      cyclical drift tube and these pulses are accumulated prior to initiation of the
      mobility measurements. Using this ion trapping approach, it was possible to
      examine ions that traversed between 1.83 and 182.86 m (from 1 to 100 cycles).
      Overall, we observe that instrumental resolving power improves with increasing
      cycle numbers; at 100 cycles, a resolving power in excess of 1000 can be
      achieved. The utility of this method as a means of distinguishing between
      analytes is demonstrated by examining the well-characterized model peptides
      substance P, angiotensin II, and bradykinin. 

PMID- 23855482
TI  - Chemically triggered C-ON bond homolysis in alkoxyamines. 6. Effect of the
      counteranion.
AB  - We showed (J. Org. Chem. 2012, 77, 9634) that the activation by methylation of
      pyridyl-based alkoxyamine 1 increased with the hydrogen bond donor properties of
      solvents. In this paper, activation of 1 by protonation with acids, CF3COOH and
      CSA, in tert-butylbenzene (t-BuPh) and in H2O/MeOH afforded, with CF3COOH, k(d)
      28-fold larger in H2O/MeOH than in t-BuPh, whereas it was only 4-fold larger when
      CSA was used. This puzzling observation was ascribed to the dissociation of the
      intimate ion pair.

PMID- 23855481
TI  - Seroepidemiology of human enterovirus71 and coxsackievirusA16 among children in
      Guangdong province, China.
AB  - BACKGROUND: Hand, foot and mouth disease (HFMD) is a common pediatric illness.
      Mainly induced by the Enterovirus 71 and Coxsackievirus A 16 infections, the
      frequently occurred HFMD outbreaks have become a serious public health problem in
      Southeast Asia. Currently,only a few studies have investigated the human immunity
      to HFMD in China. In this study, we conducted a cohort study in Guangdong
      province, China. METHODS: Stored serum samples from children less than 10 years
      old were analyzed. The levels of EV71 and CA16 specific antibodies before, during
      and shortly after the 2008 large outbreak of HFMD were evaluated by the
      microneutralization test. The geometric mean titer (GMT) was calculated and
      compared. Statistical significance was taken as P < 0.05. RESULTS: The
      seroprevalence data showed a continuous circulation of EV71 and CA16 in Guangdong
      province China in 2007-2009. The low positive rate in 2009 correlated well with
      the unprecedented outbreak of HFMD in 2010. Age related increase of
      seroprevalence was identified in 1-3 years old children for EV71 and in 1-5 years
      old children for CA16 in Guangdong province. High GMT of EV71 and CA16 antibody
      titers were also found for these age groups. CONCLUSIONS: All of the above
      findings indicated common infections for these age groups. And they should
      clearly be at the top of the priority in periodical seroprevalence survey and
      future vaccination campaign.

PMID- 23855483
TI  - OH-initiated oxidation mechanisms and kinetics of 2,4,4'-Tribrominated diphenyl
      ether.
AB  - 2,4,4'-Tribromodiphenyl ether (BDE-28) was selected as a typical congener of
      polybrominated diphenyl ethers (PBDEs) to examine its fate both in the atmosphere
      and in water solution. All the calculations were obtained at the ground state.
      The mechanism result shows that the oxidations between BDE-28 and OH radicals are
      highly feasible especially at the less-brominated phenyl ring. Hydroxylated
      dibrominated diphenyl ethers (OH-PBDEs) are formed through direct bromine
      substitution reactions (P1~P3) or secondary reactions of OH-adducts (P4~P8).
      Polybrominated dibenzo-p-dioxins (PBDDs) resulting from o-OH-PBDEs are favored
      products compared with polybrominated dibenzofurans (PBDFs) generated by
      bromophenols and their radicals. The complete degradation of OH adducts in the
      presence of O2/NO, which generates unsaturated ketones and aldehydes, is less
      feasible compared with the H-abstraction pathways by O2. Aqueous solution reduces
      the feasibility between BDE-28 and the OH radical. The rate constant of BDE-28
      and the OH radical is determined to be 1.79 * 10(-12) cm(3) molecule(-1) s(-1)
      with an atmospheric lifetime of 6.7 days. 

PMID- 23855484
TI  - Mass production of SNP markers in a nonmodel passerine bird through RAD
      sequencing and contig mapping to the zebra finch genome.
AB  - Here, we present an adaptation of restriction-site-associated DNA sequencing (RAD
      seq) to the Illumina HiSeq2000 technology that we used to produce SNP markers in
      very large quantities at low cost per unit in the Reunion grey white-eye
      (Zosterops borbonicus), a nonmodel passerine bird species with no reference
      genome. We sequenced a set of six pools of 18-25 individuals using a single
      sequencing lane. This allowed us to build around 600 000 contigs, among which at
      least 386 000 could be mapped to the zebra finch (Taeniopygia guttata) genome.
      This yielded more than 80 000 SNPs that could be mapped unambiguously and are
      evenly distributed across the genome. Thus, our approach provides a good
      illustration of the high potential of paired-end RAD sequencing of pooled DNA
      samples combined with comparative assembly to the zebra finch genome to build
      large contigs and characterize vast numbers of informative SNPs in nonmodel
      passerine bird species in a very efficient and cost-effective way. 

PMID- 23855485
TI  - Evidence for a role of neural pathways in dermographism.

PMID- 23855486
TI  - Acacetin inhibits expression of E-selectin on endothelial cells through
      regulation of the MAP kinase signaling pathway and activation of NF-kappaB.
AB  - Since E-selectin-mediated adhesion of leukocytes or tumor cells to the vascular
      endothelium is a key early event in the initiation of inflammatory response and
      cancer metastasis, E-selectin inhibition is thought to be a good target for
      therapeutic intervention. Several flavones have been shown to have anti
      inflammatory and anticancer properties. In the present study, we investigated the
      effects of plant flavones on expression of E-selectin in human umbilical vein
      endothelial cells. Among 11 flavones, acacetin strongly inhibited TNF-alpha
      induced E-selectin expression in HUVECs. Acacetin suppressed the TNF-alpha
      induced phosphorylation of p38 but did not inhibit TNF-alpha-induced
      phosphorylations of JNK and ERK. Acacetin also inhibited the activation of NF
      kappaB by stimulation with TNF-alpha. Furthermore, adhesion of monocytes to TNF
      alpha-treated endothelial cells was inhibited by cotreatment with acacetin. These
      results suggest that acacetin inhibits the expression of E-selectin by regulation
      of the p38 MAPK signaling pathway and activation of NF-kappaB.

PMID- 23855487
TI  - Benznidazole modulates cell proliferation in acute leukemia cells.
AB  - CONTEXT: We have previously reported that benznidazole (BZL), known for its
      trypanocidal action, has anti-proliferative activity against different cell lines
      like HeLa and Raw 264.7 among others. At the moment, it has not been reported if
      the anti-proliferative effect of BZL is similar for non-adherent hematopoietic
      cells like was reported for adherent cancer cell lines. OBJECTIVE: We aimed to
      investigate the efficacy of BZL on the growth of the leukemic cell lines THP-1
      and OCI/AML3. MATERIALS AND METHODS: We evaluated cell proliferation by [3H]
      thymidine incorporation and MTT reduction as well as cell death by lactate
      dehydrogenase (LDH) activity. We assessed apoptosis by flow cytometry for
      detection of annexin V-positive and propidium iodide-negative cells, along with
      nuclear morphology by diamidino-2-phenolindole (DAPI) staining. Western blot
      studies were performed to evaluate changes in cell cycle proteins in BZL-treated
      cells. RESULTS: BZL significantly reduced proliferation of both cell lines
      without inducing cell death. Likewise it produced no significant differences in
      apoptosis between treated cells and controls. In addition, flow cytometry
      analysis indicated that BZL caused a larger number of THP-1 cells in G0/G1 phase
      and a smaller number of cells in S phase than controls. This was accompanied with
      an increase in the expression of the CDK inhibitor p27 and of cyclin D1, with no
      significant differences in the protein levels of CDK1, CDK2, CDK4, cyclins E, A
      and B as compared to controls. CONCLUSION: BZL inhibits the proliferation of
      leukemic non-adherent cells by controlling cell cycle at G0/G1 cell phase through
      up-regulation of p27.

PMID- 23855488
TI  - Migration from low- to high-risk countries: a qualitative study of perceived risk
      of breast cancer and the influence on participation in mammography screening
      among migrant women in Denmark.
AB  - Migrants are less likely to participate in mammography screening programmes
      compared with local-born populations in Europe. We explored perceptions of breast
      cancer risk and the influence on participation in mammography screening
      programmes among migrant women born in countries with low incidence rates of
      breast cancer. We conducted eight individual interviews and six group interviews
      including a total of 29 women aged 50-69 years living in Copenhagen, Denmark.
      Women were migrants born in Somalia, Turkey, Pakistan or Arab countries.
      Phenomenological analysis was used. Breast cancer was perceived to be caused by
      multiple factors, including genetics, health behaviour, stress, fertility and
      breastfeeding. Some women perceived breast cancer to be more prevalent in Denmark
      as compared with their country of birth, and perceived their risk of developing
      breast cancer to increase with length of stay in Denmark. Although most women
      agreed on the relevance of mammography screening, other cancers, chronic and
      infectious diseases and mental health problems were mentioned as equally or more
      important to target in public health programmes. A life course perspective
      comprising previous and current circumstances in country of birth as well as
      immigration country is important for understanding and influencing the screening
      behaviour of migrants. 

PMID- 23855489
TI  - Identification of cellular proteome using two-dimensional difference gel
      electrophoresis in ST cells infected with transmissible gastroenteritis
      coronavirus.
AB  - BACKGROUND: Transmissible gastroenteritis coronavirus (TGEV) is an
      enteropathogenic coronavirus that causes diarrhea in pigs, which is correlated
      with high morbidity and mortality in suckling piglets. Information remains
      limited about the comparative protein expression of host cells in response to
      TGEV infection. In this study, cellular protein response to TGEV infection in
      swine testes (ST) cells was analyzed, using the proteomic method of two
      dimensional difference gel electrophoresis (2D DIGE) coupled with MALDI-TOF
      TOF/MS identification. RESULTS: 33 differentially expressed protein spots, of
      which 23 were up-regulated and 10 were down-regulated were identified. All the
      protein spots were successfully identified. The identified proteins were involved
      in the regulation of essential processes such as cellular structure and
      integrity, RNA processing, protein biosynthesis and modification, vesicle
      transport, signal transduction, and the mitochondrial pathway. Western blot
      analysis was used to validate the changes of alpha tubulin, keratin 19, and
      prohibitin during TGEV infection. CONCLUSIONS: To our knowledge, we have
      performed the first analysis of the proteomic changes in host cell during TGEV
      infection. 17 altered cellular proteins that differentially expressed in TGEV
      infection were identified. The present study provides protein-related information
      that should be useful for understanding the host cell response to TGEV infection
      and the underlying mechanism of TGEV replication and pathogenicity.

PMID- 23855490
TI  - A novel human anti-VCAM-1 monoclonal antibody ameliorates airway inflammation and
      remodelling.
AB  - Asthma is a chronic inflammatory disease induced by Type 2 helper T cells and
      eosinophils. Vascular cell adhesion molecule-1 (VCAM-1) has been implicated in
      recruiting eosinophils and lymphocytes to pathological sites in asthma as a
      regulatory receptor. Accordingly, monoclonal antibody (mAb) against VCAM-1 may
      attenuate allergic inflammation and pathophysiological features of asthma. We
      attempted to evaluate whether a recently developed human anti-VCAM-1 mAb can
      inhibit the pathophysiological features of asthma in a murine asthma model
      induced by ovalbumin (OVA). Leucocyte adhesion inhibition assay was performed to
      evaluate the in vitro blocking activity of human anti-VCAM-1 mAb. OVA-sensitized
      BALB/c mice were treated with human anti-VCAM-1 mAb or isotype control Ab before
      intranasal OVA challenge. We evaluated airway hyperresponsiveness (AHR) and
      bronchoalveolar lavage fluid analysis, measured inflammatory cytokines and
      examined histopathological features. The human anti-VCAM-1 mAb bound to human and
      mouse VCAM-1 molecules and inhibited adhesion of human leucocytes in vitro. AHR
      and inflammatory cell counts in bronchoalveolar lavage fluid were reduced in mice
      treated with human anti-VCAM-1 mAb as compared with a control Ab. The levels of
      interleukin (IL)-5 and IL-13, as well as transforming growth factor-beta, in lung
      tissue were decreased in treated mice. Human anti-VCAM-1 mAb reduced goblet cell
      hyperplasia and peribronchial fibrosis. In vivo VCAM-1 expression decreased in
      the treated group. In conclusion, human anti-VCAM-1 mAb attenuated allergic
      inflammation and the pathophysiological features of asthma in OVA-induced murine
      asthma model. The results suggested that human anti-VCAM-1 mAb could potentially
      be used as an additional anti-asthma therapeutic medicine. 

PMID- 23855491
TI  - The Network Modification (NeMo) Tool: elucidating the effect of white matter
      integrity changes on cortical and subcortical structural connectivity.
AB  - Accurate prediction of brain dysfunction caused by disease or injury requires the
      quantification of resultant neural connectivity changes compared with the normal
      state. There are many methods with which to assess anatomical changes in
      structural or diffusion magnetic resonance imaging, but most overlook the
      topology of white matter (WM) connections that make up the healthy brain network.
      Here, a new neuroimaging software pipeline called the Network Modification (NeMo)
      Tool is presented that associates alterations in WM integrity with expected
      changes in neural connectivity between gray matter regions. The NeMo Tool uses a
      large reference set of healthy tractograms to assess implied network changes
      arising from a particular pattern of WM alteration on a region- and network-wise
      level. In this way, WM integrity changes can be extrapolated to the cortices and
      deep brain nuclei, enabling assessment of functional and cognitive alterations.
      Unlike current techniques that assess network dysfunction, the NeMo tool does not
      require tractography in pathological brains for which the algorithms may be
      unreliable or diffusion data are unavailable. The versatility of the NeMo Tool is
      demonstrated by applying it to data from patients with Alzheimer's disease,
      fronto-temporal dementia, normal pressure hydrocephalus, and mild traumatic brain
      injury. This tool fills a gap in the quantitative neuroimaging field by enabling
      an investigation of morphological and functional implications of changes in
      structural WM integrity.

PMID- 23855492
TI  - Mechanical ventilation in a dog with acetylcholinesterase inhibitor toxicosis.
AB  - BACKGROUND: To describe a case of acetylcholinesterase inhibitor (AChEI)
      toxicosis with ventilatory failure that was successfully treated with mechanical
      ventilation (MV). KEY FINDINGS: A 7-year-old, female spayed German Short-haired
      Pointer, presented with acute onset ptyalism, generalized muscle tremors, and
      diarrhea. Physical examination findings included evidence of muscarinic
      overstimulation in the parasympathetic nervous system (eg, diarrhea, ptyalism,
      lacrimation), and nicotinic overstimulation in the sympathetic nervous system
      (tachycardia), central nervous system (agitation), and the neuromuscular junction
      (eg, diffuse muscle fasciculations, tetraparesis). Point-of-care testing
      demonstrated hyperlactatemic metabolic acidosis and respiratory acidosis
      (hypoventilation). Hypoventilation progressed to respiratory failure and the dog
      lost its gag reflex necessitating emergency endotracheal intubation and MV.
      Additional treatments included atropine, parenteral antimicrobials (for
      aspiration pneumonia), pralidoxime, and supportive care. Weaning from the
      ventilator was achieved in 4 days. The dog was administered supplemental oxygen
      for 24 hours, and discharged 48 hours later with improved neurologic function and
      normal respiratory drive. Whole blood acetylcholinesterase activities measured on
      day 0, 2, and 4 and were consistent with AChEI toxicity. NEW OR UNIQUE
      INFORMATION PROVIDED: Specific AChEI toxicity (ie, carbamate and organophosphate)
      has been reported in the veterinary literature with good prognosis for survival
      and hospital discharge. While the existing veterinary literature suggests that
      ventilatory failure is rare in this disease syndrome, consideration for treatment
      with MV must be made for patients that develop respiratory failure (associated
      with hypoventilation, bronchoconstriction, bronchorrhea, or aspiration
      pneumonia).

PMID- 23855493
TI  - Portal vein omentin is increased in patients with liver cirrhosis but is not
      associated with complications of portal hypertension.
AB  - BACKGROUND: Omentin is a visceral fat-derived adipokine associated with
      endothelium-dependent vasodilation. Impaired endothelial function is a major
      cause of portal hypertension in liver cirrhosis. The aim was to assess
      associations of omentin with systemic markers of endothelial function, namely
      arginine and asymmetric dimethylarginine (ADMA) and complications of portal
      hypertension in liver cirrhosis. MATERIALS AND METHODS: Systemic omentin was
      measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and
      hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver
      healthy controls. ADMA and arginine were determined in SVS of the patients by
      ELISA. RESULTS: Omentin is elevated in PVS and tends to be increased in SVS and
      HVS of patients with liver cirrhosis compared with controls. Omentin is
      principally expressed in visceral fat, and PVS omentin tends to be higher than
      SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly
      removed from the circulation by the liver. Omentin in serum is not associated
      with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not
      affected in patients with ascites. HVS omentin tends to be reduced in patients
      with large varices compared with patients without/with small varices.
      Arginine/ADMA ratio is reduced in patients with massive ascites but is not
      associated with variceal size. Further, Arginine/ADMA ratio does not correlate
      with omentin. CONCLUSION: Current data show that PVS omentin is increased in
      liver cirrhosis but is not associated with complications of portal hypertension.

PMID- 23855494
TI  - The hippocampus: a manifesto for change.
AB  - We currently lack a unified and mechanistic account of how the hippocampus
      supports a range of disparate cognitive functions that includes episodic memory,
      imagining the future, and spatial navigation. Here, we argue that in order to
      leverage this long-standing issue, traditional notions regarding the architecture
      of memory should be eschewed. Instead, we invoke the idea that scenes are central
      to hippocampal information processing. This view is motivated by mounting
      evidence that the hippocampus is constantly constructing spatially coherent
      scenes, automatically anticipating and synthesizing representations of the world
      beyond the immediate sensorium. By characterizing the precise relationship
      between scenes and the hippocampus, we believe a theoretically enriched
      understanding of its fundamental role and its breakdown in pathology can emerge.

PMID- 23855495
TI  - I can see, hear, and smell your fear: comparing olfactory and audiovisual media
      in fear communication.
AB  - Recent evidence suggests that humans can become fearful after exposure to
      olfactory fear signals, yet these studies have reported the effects of fear
      chemosignals without examining emotion-relevant input from traditional
      communication modalities (i.e., vision, audition). The question that we pursued
      here was therefore: How significant is an olfactory fear signal in the broader
      context of audiovisual input that either confirms or contradicts olfactory
      information? To test this, we manipulated olfactory (fear, no fear) and
      audiovisual (fear, no fear) information and demonstrated that olfactory fear
      signals were as potent as audiovisual fear signals in eliciting a fearful facial
      expression. Irrespective of confirmatory or contradictory audiovisual
      information, olfactory fear signals produced by senders induced fear in receivers
      outside of conscious access. These findings run counter to traditional views that
      emotions are communicated exclusively via visual and linguistic channels.

PMID- 23855496
TI  - P-curve: a key to the file-drawer.
AB  - Because scientists tend to report only studies (publication bias) or analyses (p
      hacking) that "work," readers must ask, "Are these effects true, or do they
      merely reflect selective reporting?" We introduce p-curve as a way to answer this
      question. P-curve is the distribution of statistically significant p values for a
      set of studies (ps < .05). Because only true effects are expected to generate
      right-skewed p-curves-containing more low (.01s) than high (.04s) significant p
      values--only right-skewed p--curves are diagnostic of evidential value. By
      telling us whether we can rule out selective reporting as the sole explanation
      for a set of findings, p-curve offers a solution to the age-old inferential
      problems caused by file-drawers of failed studies and analyses.

PMID- 23855497
TI  - Using imagery perspective to access two distinct forms of self-knowledge:
      associative evaluations versus propositional self-beliefs.
AB  - When mentally simulating life events, people may visualize them from either an
      actor's 1st-person or observer's 3rd-person visual perspective. Two experiments
      demonstrated that visual perspective differentially determines reliance on 2
      distinct forms of self-knowledge: associative evaluations of the simulated
      environment and propositional self-beliefs about relevant values and preferences.
      Implicit measures indexed associative evaluations of environmental stimuli
      (political candidates, outgroups); explicit measures indexed propositional self
      beliefs about relevant personal values or preferences. A separate session
      manipulated participants' visual perspective for mentally simulating a pertinent
      event (voting, interracial interaction) as they forecasted their behavior or
      feelings if that event occurred. Forecasts corresponded more closely with
      associative evaluations from the 1st-person than 3rd-person perspective but more
      closely with propositional self-beliefs from the 3rd-person than 1st-person.
      Results have practical implications for channeling the power of mental simulation
      to desired ends and theoretical implications for understanding the pathways by
      which imagery and mental simulation shape cognition.

PMID- 23855498
TI  - Spinal cord infarction in diabetic pregnancy: a case report.
AB  - Spinal cord infarction (SCI) is uncommon as compared to cerebral stroke.
      Moreover, SCI during pregnancy is rare. Here, we report a case of SCI in diabetic
      pregnancy, properly diagnosed, promptly treated, and a good prognosis achieved. A
      38-year-old, pregnant woman, para 1, with type 1 diabetes mellitus on insulin
      since 14 years of age, was admitted to our hospital for paresthesia and numbness
      in the lower left side of the body, with movement disturbances. On the basis of
      the temporal profile of the onset and the multiple resonance imaging scans, SCI
      was diagnosed. Steroid pulse therapy and low-dose aspirin administration was
      initiated. Her symptoms were improved and discharged. A repeat cesarean section
      was performed at 37 weeks of gestation and her postoperative course was
      uneventful. Her daily activities were not hindered severely, though she
      experienced defecation discomfort. 

PMID- 23855499
TI  - Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose
      matrix tablets: distribution of atoms and carrier and texture analysis.
AB  - Although release profiles of drug from hydrophilic matrices have been well
      recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and
      atoms inside of internal structures of hydrophilic HPMC matrices has not been
      characterized. In this paper, drug release mechanism from HPMC matrix tablet was
      investigated based on the release behaviors of HPMC, physical properties of
      gelled HPMC tablet and atomic distributions of formulation components using
      diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose
      (HPMC 6, 4,000 and 100,000 mPa.s), chlorpheniramine maleate (CPM) as a model and
      fumed silicon dioxide (Aerosil((r)) 200) was prepared via direct compression. The
      distribution of atoms and HPMC imaging were characterized using scanning electron
      microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared
      (NIR) analysis, respectively as a function of time. A texture analyzer was also
      used to characterize the thickness and maintenance of gel layer of HPMC matrix
      tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time
      against the square root of time. High viscosity grades of HPMC gave retarded
      release rate because of the greater swelling and gel thickness as characterized
      by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6
      mPa.s) quickly leached out onto the surface of the tablet, while the high
      viscosity-grade HPMC (4000 mPa.s) formed much thicker gel layer around the tablet
      and maintained longer via slow erosion, resulting in retarded drug release. The
      atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen)
      and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with
      the dissolution behaviors of drug as a function of time. The use of imaging and
      texture analyses could be applicable to explain the release- modulating mechanism
      of hydrophilic HPMC matrix tablets. 

PMID- 23855500
TI  - Stepping into a map: initial heading direction influences spatial memory
      flexibility.
AB  - Learning a novel environment involves integrating first-person perceptual and
      motoric experiences with developing knowledge about the overall structure of the
      surroundings. The present experiments provide insights into the parallel
      development of these egocentric and allocentric memories by intentionally
      conflicting body- and world-centered frames of reference during learning, and
      measuring outcomes via online and offline measures. Results of two experiments
      demonstrate faster learning and increased memory flexibility following route
      perspective reading (Experiment 1) and virtual navigation (Experiment 2) when
      participants begin exploring the environment on a northward (vs. any other
      direction) allocentric heading. We suggest that learning advantages due to
      aligning body-centered (left/right/forward/back) with world-centered (NSEW)
      reference frames are indicative of three features of spatial memory development
      and representation. First, memories for egocentric and allocentric information
      develop in parallel during novel environment learning. Second, cognitive maps
      have a preferred orientation relative to world-centered coordinates. Finally,
      this preferred orientation corresponds to traditional orientation of physical
      maps (i.e., north is upward), suggesting strong associations between daily
      perceptual and motor experiences and the manner in which we preferentially
      represent spatial knowledge. 

PMID- 23855501
TI  - Some considerations on the definition of risk based on concepts of systems theory
      and probability.
AB  - The concept of risk has been applied in many modern science and technology
      fields. Despite its successes in many applicative fields, there is still not a
      well-established vision and universally accepted definition of the principles and
      fundamental concepts of the risk assessment discipline. As emphasized recently,
      the risk fields suffer from a lack of clarity on their scientific bases that can
      define, in a unique theoretical framework, the general concepts in the different
      areas of application. The aim of this article is to make suggestions for another
      perspective of risk definition that could be applied and, in a certain sense,
      generalize some of the previously known definitions (at least in the fields of
      technical and scientific applications). By drawing on my experience of risk
      assessment in different applicative situations (particularly in the risk
      estimation for major industrial accidents, and in the health and ecological risk
      assessment for contaminated sites), I would like to revise some general and
      foundational concepts of risk analysis in as consistent a manner as possible from
      the axiomatic/deductive point of view. My proposal is based on the fundamental
      concepts of the systems theory and of the probability. In this way, I try to
      frame, in a single, broad, and general theoretical context some fundamental
      concepts and principles applicable in many different fields of risk assessment. I
      hope that this article will contribute to the revitalization and stimulation of
      useful discussions and new insights into the key issues and theoretical
      foundations of risk assessment disciplines. 

PMID- 23855502
TI  - The potential mechanisms of Abeta-receptor for advanced glycation end-products
      interaction disrupting tight junctions of the blood-brain barrier in Alzheimer's
      disease.
AB  - The receptor for advanced glycation end-products (RAGE) is a multiligand membrane
      receptor that has been implicated in the cytotoxicity effects of beta-amyloid
      protein (Abeta) in AD. Positive feedback mechanism of RAGE within blood-brain
      barrier (BBB) and/or cells inside the brain is proposed, including interaction
      with Abeta stimulating activation of proinflammatory cytokines, release of
      reactive oxygen species (ROS), which leads to neuron damage and BBB dysfunction.
      RAGE is the main factor mediating Abeta cytotoxicity. Attenuation of RAGE
      activity may inhibit Abeta from accumulation in the cerebral blood vessels and
      prevent neurotoxicity. Furthermore, RAGE may serve as a therapeutic target for
      Alzheimer's disease by inhibiting pathophysiological consequences of Abeta-RAGE
      interaction. Tight junctions (TJ) are identified as the basic structure of the
      BBB and RAGE-mediated Abeta cytotoxicity to the brain microvascular endothelial
      cells (BMEC), resulting in damaged BBB structural integrity. However, the
      potential mechanism is poorly studied. 

PMID- 23855503
TI  - Intensified fractional CO2 laser-assisted photodynamic therapy vs. laser alone
      for organ transplant recipients with multiple actinic keratoses and wart-like
      lesions: a randomized half-side comparative trial on dorsal hands.
AB  - BACKGROUND: Photodynamic therapy (PDT) is a well-documented treatment for actinic
      keratosis (AK), but achieves inferior efficacy in organ transplant recipients
      (OTRs), particularly in acral regions. Ablative fractional laser (AFXL)
      intensifies the PDT response and may improve the efficacy of AK clearance when
      used as monotherapy. OBJECTIVES: To compare the efficacy of a single treatment
      with AFXL-assisted PDT vs. AFXL alone for difficult-to-treat AKs and wart-like
      lesions (WLLs) in OTRs. METHODS: Ten OTRs were included with a total of 680 AKs
      (severity grade I-III) and 409 WLLs on the dorsal hands. Both hands were
      initially treated with targeted fractional ablation of thick keratotic lesions
      followed by AFXL field treatment. Treatment regions were then randomized to (i)
      PDT (AFXL-PDT) or (ii) no further treatment (AFXL). The primary end point was
      complete response (CR) at 4 months after treatment; secondary end points were
      improvement of AK severity grade, overall patient assessment of efficacy and
      tolerability of treatments. RESULTS: CR of AKs was significantly higher for AFXL
      PDT (73%) compared with AFXL alone (31%) (P = 0.002). AFXL-PDT improved 82% of
      AKs to lower lesion grades compared with 52% after AFXL alone (P = 0.008). For
      WLLs, the rate of CR was 37% for AFXL-PDT compared with 14% for AFXL (P = 0.02).
      Overall assessment showed a preference for AFXL-PDT compared with AFXL (AFXL-PDT,
      n = 8; AFXL, n = 0; equal, n = 2). Mild pigment changes were observed in four
      patients (AFXL-PDT, n = 3; AFXL, n = 1). No scarring was observed. CONCLUSIONS:
      AFXL-PDT is more effective than AFXL in the treatment of acral AKs and WLLs in
      OTRs.

PMID- 23855504
TI  - The grounded psychometric development and initial validation of the Health
      Literacy Questionnaire (HLQ).
AB  - BACKGROUND: Health literacy has become an increasingly important concept in
      public health. We sought to develop a comprehensive measure of health literacy
      capable of diagnosing health literacy needs across individuals and organisations
      by utilizing perspectives from the general population, patients, practitioners
      and policymakers. METHODS: Using a validity-driven approach we undertook grounded
      consultations (workshops and interviews) to identify broad conceptually distinct
      domains. Questionnaire items were developed directly from the consultation data
      following a strict process aiming to capture the full range of experiences of
      people currently engaged in healthcare through to people in the general
      population. Psychometric analyses included confirmatory factor analysis (CFA) and
      item response theory. Cognitive interviews were used to ensure questions were
      understood as intended. Items were initially tested in a calibration sample from
      community health, home care and hospital settings (N=634) and then in a
      replication sample (N=405) comprising recent emergency department attendees.
      RESULTS: Initially 91 items were generated across 6 scales with agree/disagree
      response options and 5 scales with difficulty in undertaking tasks response
      options. Cognitive testing revealed that most items were well understood and only
      some minor re-wording was required. Psychometric testing of the calibration
      sample identified 34 poorly performing or conceptually redundant items and they
      were removed resulting in 10 scales. These were then tested in a replication
      sample and refined to yield 9 final scales comprising 44 items. A 9-factor CFA
      model was fitted to these items with no cross-loadings or correlated residuals
      allowed. Given the very restricted nature of the model, the fit was quite
      satisfactory: chi2WLSMV(866 d.f.) = 2927, p<0.000, CFI = 0.936, TLI = 0.930,
      RMSEA = 0.076, and WRMR = 1.698. Final scales included: Feeling understood and
      supported by healthcare providers; Having sufficient information to manage my
      health; Actively managing my health; Social support for health; Appraisal of
      health information; Ability to actively engage with healthcare providers;
      Navigating the healthcare system; Ability to find good health information; and
      Understand health information well enough to know what to do. CONCLUSIONS: The
      HLQ covers 9 conceptually distinct areas of health literacy to assess the needs
      and challenges of a wide range of people and organisations. Given the validity
      driven approach, the HLQ is likely to be useful in surveys, intervention
      evaluation, and studies of the needs and capabilities of individuals.

PMID- 23855506
TI  - Bulk transport and interfacial transfer dynamics of photogenerated carriers in
      CdSe quantum dot solid electrodes.
AB  - Practical solar-to-fuel conversion applications of quantum-confined semiconductor
      crystals require their integration into electrodes. We show that photogenerated
      electrons in quantum dot solid electrodes can be transported to the aqueous
      interface to reduce methyl viologen with 100% quantum efficiency and an effective
      time constant of 12 +/- 2 ps. The charge separated state had a half-life of 200
      +/- 10 ns, limited by hole transport within the solid. 

PMID- 23855507
TI  - Low testosterone and diabetes.
AB  - There have been a lot of discussions concerning the relationship between
      testosterone serum levels in males and diabetes. Low testosterone is commonly
      associated with type 2 diabetes and metabolic syndrome. Testosterone therapy
      alters the body composition in a metabolically favorable manner. In this article
      we shed some light on the bidirectional relation between hypotestosteronemia and
      diabetes discussing also the possible mechanisms and the benefit of treatment. 

PMID- 23855505
TI  - Identification of Lactobacillus strains with probiotic features from the
      bottlenose dolphin (Tursiops truncatus).
AB  - AIMS: In order to develop complementary health management strategies for marine
      mammals, we used culture-based and culture-independent approaches to identify
      gastrointestinal lactobacilli of the common bottlenose dolphin, Tursiops
      truncatus. METHODS AND RESULTS: We screened 307 bacterial isolates from oral and
      rectal swabs, milk and gastric fluid, collected from 38 dolphins in the U.S. Navy
      Marine Mammal Program, for potentially beneficial features. We focused our search
      on lactobacilli and evaluated their ability to modulate TNF secretion by host
      cells and inhibit growth of pathogens. We recovered Lactobacillus salivarius
      strains which secreted factors that stimulated TNF production by human monocytoid
      cells. These Lact. salivarius isolates inhibited growth of selected marine mammal
      and human bacterial pathogens. In addition, we identified a novel Lactobacillus
      species by culture and direct sequencing with 96.3% 16S rDNA sequence similarity
      to Lactobacillus ceti. CONCLUSIONS: Dolphin-derived Lact. salivarius isolates
      possess features making them candidate probiotics for clinical studies in marine
      mammals. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to isolate
      lactobacilli from dolphins, including a novel Lactobacillus species and a new
      strain of Lact. salivarius, with potential for veterinary probiotic applications.
      The isolation and identification of novel Lactobacillus spp. and other indigenous
      microbes from bottlenose dolphins will enable the study of the biology of
      symbiotic members of the dolphin microbiota and facilitate the understanding of
      the microbiomes of these unique animals.

PMID- 23855508
TI  - Incretin-based therapies for type 2 diabetes mellitus: effects on insulin
      resistance.
AB  - Insulin resistance has been associated with the development of type 2 diabetes,
      obesity, hypertension, dyslipidemia, atherosclerosis, and thus with increased
      cardiovascular morbidity and mortality. Insulin resistance precedes the onset of
      type 2 diabetes by many years. Targeting the pathophysiologic defects that
      characterize the onset of diabetes is more likely to achieve a durable glucose
      control and to delay disease progression. Incretins are gut-derived peptides that
      stimulate in a glucose-dependent mechanism insulin secretion and action. Glucose
      like peptide 1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors
      both decrease fasting and postprandial glucose levels. In addition, GLP-1
      analogues promote weight loss and exert a favorable effect on several
      cardiovascular risk factors. Data from human and experimental studies implicate
      that GLP-1 analogues and to a less extend DPP-4 inhibitors enhance insulin
      sensitivity. This review summarizes the current knowledge regarding the impact of
      GLP-1 analogues and DPP-4 inhibitors on insulin resistance. 

PMID- 23855509
TI  - Goto-Kakizaki rats: its suitability as non-obese diabetic animal model for
      spontaneous type 2 diabetes mellitus.
AB  - beta-cell dysfunction and apoptosis are recognized as a major cause of
      insufficient insulin secretion in response to high blood glucose and metabolic
      demand. As a consequence, type 2 diabetes mellitus (T2DM) is known to occur.
      Taking into account the etiology of T2DM, to conduct investigational studies
      directly on human diabetic patients seems to be unsuitable; thereby, various
      animal models have been established to investigate the pathogenesis of T2DM.
      Among these models, Goto-Kakizaki (GK) rats have been considered as one of the
      best non-obese type 2 diabetic animal model. GK rats exhibit valuable
      characteristic tools that are more or less common and functionally present in
      human diabetic patients. This animal model is considered appropriate to inspect
      various pathologic mechanisms of T2DM. Thereby, in our present article, we have
      comprehensively summarized the information relating the characteristics of
      abnormalities including a description of assorted mechanisms involved in
      pathogenesis of T2DM in GK rats. This might help to investigate various aspects
      of spontaneous T2DM. 

PMID- 23855510
TI  - A review of the efficacy of neuromuscular electrical stimulation in critically
      ill patients.
AB  - BACKGROUND: Muscle wasting in critical illness has been identified as a major
      clinical concern which can lead to persistent muscle weakness, impede recovery
      and limit physical function and quality of life in survivors. Neuromuscular
      electrical stimulation (NMES) has been suggested as an alternative to active
      exercise in critically ill patients. OBJECTIVES: To evaluate the efficacy of NMES
      in critically ill patients by evaluating the research literature. METHODS:
      Structured database searches of the Cochrane Library, Ovid (Medline), CINHAL,
      Scopus and PEDro were completed. RESULTS: Eight papers were retrieved and
      methodological quality evaluated using the Critical Appraisal and Skills Program
      tool. The NMES protocols, outcomes and findings were analysed and, given the
      methodological heterogeneity, the study findings were synthesised as a narrative.
      Analysis showed minimal adverse effects in the use of NMES and some potential
      benefits of NMES on preservation of muscle strength, decreased duration of
      mechanical ventilation and shorter Intensive Care Unit (ICU) length of stay.
      CONCLUSIONS: Evidence of the clinical benefits of NMES in the ICU is inconclusive
      and provides minimal guidance for use in clinical practice. There is a need for
      further research in this area.

PMID- 23855512
TI  - A route to oligosaccharide-appended salicylaldehydes: useful building blocks for
      the synthesis of metal-salophen complexes.
AB  - A simple and general synthetic protocol to obtain oligosaccharide-appended
      salicylaldehydes, key intermediates for the synthesis of water-soluble metal
      salophen complexes, is here reported. Six new aldehydes have been prepared and
      fully characterized as well as the corresponding zinc- and uranyl-salophen
      complexes. These new derivatives show very good solubility in water. Preliminary
      studies on the association of compound 19-U, that is, the uranyl maltotetraose
      derivative, with hydrogen phosphate and fluoride provide very encouraging results
      and open up the possibility of using such compounds for the efficient recognition
      of anions in pure water. 

PMID- 23855511
TI  - Synthetic inhibitors of bacterial cell division targeting the GTP-binding site of
      FtsZ.
AB  - Cell division protein FtsZ is the organizer of the cytokinetic Z-ring in most
      bacteria and a target for new antibiotics. FtsZ assembles with GTP into filaments
      that hydrolyze the nucleotide at the association interface between monomers and
      then disassemble. We have replaced FtsZ's GTP with non-nucleotide synthetic
      inhibitors of bacterial division. We searched for these small molecules among
      compounds from the literature, from virtual screening (VS), and from our in-house
      synthetic library (UCM), employing a fluorescence anisotropy primary assay. From
      these screens we have identified the polyhydroxy aromatic compound UCM05 and its
      simplified analogue UCM44 that specifically bind to Bacillus subtilis FtsZ
      monomers with micromolar affinities and perturb normal assembly, as examined with
      light scattering, polymer sedimentation, and negative stain electron microscopy.
      On the other hand, these ligands induce the cooperative assembly of nucleotide
      devoid archaeal FtsZ into distinct well-ordered polymers, different from GTP
      induced filaments. These FtsZ inhibitors impair localization of FtsZ into the Z
      ring and inhibit bacterial cell division. The chlorinated analogue UCM53 inhibits
      the growth of clinical isolates of antibiotic-resistant Staphylococcus aureus and
      Enterococcus faecalis. We suggest that these interfacial inhibitors recapitulate
      binding and some assembly-inducing effects of GTP but impair the correct
      structural dynamics of FtsZ filaments and thus inhibit bacterial division,
      possibly by binding to a small fraction of the FtsZ molecules in a bacterial
      cell, which opens a new approach to FtsZ-based antibacterial drug discovery. 

PMID- 23855513
TI  - Maleimide conjugates of saxitoxin as covalent inhibitors of voltage-gated sodium
      channels.
AB  - (+)-Saxitoxin, a naturally occurring guanidinium poison, functions as a potent,
      selective, and reversible inhibitor of voltage-gated sodium ion channels (NaVs).
      Modified forms of this toxin bearing cysteine-reactive maleimide groups are
      available through total synthesis and are found to irreversibly inhibit sodium
      ion conductance in recombinantly expressed wild-type sodium channels and in
      hippocampal nerve cells. Our findings support a mechanism for covalent protein
      modification in which toxin binding to the channel pore precedes maleimide
      alkylation of a nucleophilic amino acid. Second-generation maleimide-toxin
      conjugates, which include bioorthogonal reactive groups, are also found to block
      channel function irreversibly; such compounds have potential as reagents for
      selective labeling of NaVs for live cell imaging and/or proteomics experiments. 

PMID- 23855514
TI  - Multipurpose use of the 'bear claw' (over-the-scope-clip system) to treat
      endoluminal gastrointestinal disorders.
AB  - BACKGROUND AND AIM: The 'bear-claw' or over-the-scope-clip system (OTSC; Ovesco
      Endoscopy, Tubingen, Germany) is a new clipping device developed for closure of
      large luminal gastrointestinal (GI) defects. The aim of the present study was to
      evaluate the clinical outcomes of patients treated with the OTSC. METHODS: The
      present study was an observational, open-label, retrospective, single-arm case
      series conducted at two hospitals with tertiary care endoscopy. It involved 20
      clip applications in 16 patients (median age 65.8 years [range 51-90 years],
      seven women) with GI defects from fistulas and anastomotic dehiscence and peptic
      ulcer bleeding. RESULTS: The range of indications included gastrointestinal
      bleeding (n=6), gastrocutaneous fistulas (n=3), esophagotracheal and/or
      esophagopleural fistulae (n=3), resection ofsubmucosal tumor (n=2), stent
      fixation (n=1), and anastomotic leak after esophagectomy (n=1). The overall
      success rate for the OTSC device was 75% (12 out of 16 patients). The overall per
      case success rate was 70% (14 of 20 applications). Mean follow up was 10 months
      (range 1-10). There were no complications (0%) related to endoscopy, sedation or
      application of the clipping device. CONCLUSIONS: The OTSC system is a useful
      device in a variety of clinical scenarios including the management of larger GI
      leaks and fistulas, GI bleeding, full-thickness resection of tumors, and stent
      anchoring, even in very old and frail patients.

PMID- 23855515
TI  - Mycobacterium abscessus peritonitis associated with laparoscopic gastric banding.
AB  - BACKGROUND: Mycobacterium abscessus is a rapidly growing Mycobacterium that is a
      common water contaminant in the environment. We report a case of M. abscessus
      infection with band erosion following laparoscopic gastric banding. CASE
      PRESENTATION: A 34-year-old woman developed insidiously progressing abdominal
      distension over a period of 1 year associated with abdominal pain, fatigue, night
      sweating and anorexia 4 years after laparoscopic gastric banding for obesity.
      Investigation revealed significant ascites with caseating granuloma in peritoneal
      biopsies from which M. abscessus was isolated. Band erosion with infection and
      multiple abdominal adhesions were confirmed during laparoscopic removal of the
      gastric band. To the best of our knowledge, this is the first reported case of M.
      abscessus infection after laparoscopic gastric banding surgery. We discuss the
      possible sources of infection, its indolent presentation, and therapeutic
      challenges. CONCLUSION: It is important to consider environmentally acquired
      infection in patients with signs and symptoms of infection in the presence of
      surgical prosthesis.

PMID- 23855516
TI  - Effects of pectin pentaoligosaccharide from Hawthorn ( Crataegus pinnatifida
      Bunge. var. Major) on the activity and mRNA levels of enzymes involved in fatty
      acid oxidation in the liver of mice fed a high-fat diet.
AB  - The regulatory effects of haw pectin pentaoligosaccharide (HPPS) on fatty acid
      oxidation-related enzyme activities and mRNA levels were investigated in the
      liver of high fat diet induced hyperlipidemic mice. Results showed that HPPS (150
      mg/kg for 10 weeks) significantly suppresses weight gain (32.3 +/- 0.26 and 21.1
      +/- 0.14 g for high-fat diet and HPPS groups, respectively), decreases serum
      triacylglycerol levels (1.64 +/- 0.09 and 0.91 +/- 0.02 mmol/L, respectively),
      and increases lipid excretion in feces (55.7 +/- 0.38 and 106.4 +/- 0.57 mg/g for
      total lipid, respectively), compared to high-fat diet as control. HPPS
      significantly increased the hepatic fatty acid oxidation-related enzyme
      activities of acyl-CoA oxidase, carnitine palmitoyltransferase I, 3-ketoacyl-CoA
      thiolase, and 2,4-dienoyl-CoA reductase by 53.8, 74.2, 47.1, and 24.2%,
      respectively. Meanwhile, the corresponding mRNAs were up-regulated by 89.6, 85.8,
      82.9, and 30.9%, respectively. Moreover, HPPS was able to up-regulate the gene
      and protein expressions of peroxisome proliferator-activated receptor alpha.
      Results suggest that continuous HPPS ingestion may be used as dietary therapy to
      prevent obesity and cardiovascular diseases. 

PMID- 23855517
TI  - Cat got your tongue? Using the tip-of-the-tongue state to investigate fixed
      expressions.
AB  - Despite the fact that they play a prominent role in everyday speech, the
      representation and processing of fixed expressions during language production is
      poorly understood. Here, we report a study investigating the processes underlying
      fixed expression production. "Tip-of-the-tongue" (TOT) states were elicited for
      well-known idioms (e.g., hit the nail on the head) and participants were asked to
      report any information they could regarding the content of the phrase.
      Participants were able to correctly report individual words for idioms that they
      could not produce. In addition, participants produced both figurative (e.g.,
      pretty for easy on the eye) and literal errors (e.g., hammer for hit the nail on
      the head) when in a TOT state, suggesting that both figurative and literal
      meanings are active during production. There was no effect of semantic
      decomposability on overall TOT incidence; however, participants recalled a
      greater proportion of words for decomposable rather than non-decomposable idioms.
      This finding suggests there may be differences in how decomposable and non
      decomposable idioms are retrieved during production. 

PMID- 23855518
TI  - Transcriptome sequencing of sea cucumber (Apostichopus japonicus) and the
      identification of gene-associated markers.
AB  - Sea cucumber (Apostichopus japonicus) is an ecologically and economically
      important species in East and South-East Asia. This project aimed to identify
      large numbers of gene-associated markers and differentially expressed genes
      (DEGs) after lipopolysaccharides (LPS) challenge in A. japonicus using high
      throughput transcriptome sequencing. A total of 162 million high-quality reads of
      174 million raw reads were obtained by deep sequencing using Illumina HiSeqTM
      2000 platform. Assembly of these reads generated 94 704 unigenes, with read
      length ranging from 200 to 16 153 bp (average length of 810 bp). A total of 36
      005 were identified as coding sequences (CDSs), 32 479 of which were successfully
      annotated. Based on the assembly transcriptome, we identified 142 511 high
      quality single nucleotide polymorphisms (SNPs). Among them, 33 775, 63 120 and 45
      616 were located in sequences without predicted CDS (non-CDSs), CDSs and
      untranslated regions (UTRs), respectively. These putative SNPs included 82 664
      transitions and 59 847 transversions. Totally, 89 375 (59.1%) were distributed in
      15 473 known genes. A total of 6417 microsatellites were detected in 5970
      unigenes, 3216 of which were annotated and 2481 were successfully subjected for
      primer design. The numbers of simple sequence repeats (SSRs) identified in non
      CDSs, CDSs and UTRs were 2367, 2316 and 1734. These potential SNPs and SSRs are
      expected to provide abundant resources for genetic, evolutionary and ecological
      studies in sea cucumber. Transcriptome comparison revealed 1330, 1347 and 1291
      DEGs in the coelomocytes of A. japonicus at 4 h, 24 h and 72 h after LPS
      challenge, respectively. Approximately 58.4% (1802) of total DEGs have been
      successfully annotated. 

PMID- 23855519
TI  - Review of newer anticoagulants and anti-platelet agents in acute coronary
      syndrome and cardiovascular diseases.
AB  - In the last few years three new oral anticoagulants-Dabigatran, Rivaroxaban and
      Apixaban and two new antiplatelet agents Prasugrel and Ticagrelor have been
      approved for use. Dabigatran, Rivaroxaban and Apixaban have been approved for the
      prevention of stroke and systemic embolism in non valvular Atrial Fibrillation in
      the United States. Rivaroxaban is also approved for the prevention and treatment
      of venous thromboembolism, including pulmonary embolism. These drugs have been
      shown to be non-inferior to Warfarin. These drugs do not need monitoring and have
      lesser drug interactions compared to Warfarin. The newer antiplatelet agents
      Prasugrel and Ticagrelor are more potent than Clopidogrel and are more effective
      in patients with CYP2 C19 enzyme deficiency. Both of these drugs are approved in
      acute coronary syndrome and Prasugrel is approved only in acute coronary syndrome
      with percutaneous coronary intervention. 

PMID- 23855520
TI  - Looking twice at the gender equity index for public health impact.
AB  - BACKGROUND: It has been shown that gender equity has a positive impact on the
      everyday activities of people (decision making, income allocation, application
      and observance of norms/rules) which affect their health. Gender equity is also a
      crucial determinant of health inequalities at national level; thus, monitoring is
      important for surveillance of women's and men's health as well as for future
      health policy initiatives. The Gender Equity Index (GEI) was designed to show
      inequity solely towards women. Given that the value under scrutiny is equity, in
      this paper a modified version of the GEI is proposed, the MGEI, which highlights
      the inequities affecting both sexes. METHODS: Rather than calculating gender gaps
      by means of a quotient of proportions, gaps in the MGEI are expressed in absolute
      terms (differences in proportions). The Spearman's rank coefficient, calculated
      from country rankings obtained according to both indexes, was used to evaluate
      the level of concordance between both classifications. To compare the degree of
      sensitivity and obtain the inequity by the two methods, the variation coefficient
      of the GEI and MGEI values was calculated. RESULTS: Country rankings according to
      GEI and MGEI values showed a high correlation (rank coef. = 0.95). The MGEI
      presented greater dispersion (43.8%) than the GEI (19.27%). Inequity towards men
      was identified in the education gap (rank coef. = 0.36) when using the MGEI.
      According to this method, many countries shared the same absolute value for
      education but with opposite signs, for example Azerbaijan (-0.022) and Belgium
      (0.022), reflecting inequity towards women and men, respectively. This also
      occurred in the empowerment gap with the technical and professional job component
      (Brunei:-0.120 vs. Australia, Canada Iceland and the U.S.A.: 0.120). CONCLUSION:
      The MGEI identifies and highlights the different areas of inequities between
      gender groups. It thus overcomes the shortcomings of the GEI related to the aim
      for which this latter was created, namely measuring gender equity, and is
      therefore of great use to policy makers who wish to understand and monitor the
      results of specific equity policies and to determine the length of time for which
      these policies should be maintained in order to correct long-standing structural
      discrimination against women.

PMID- 23855521
TI  - Pneumomediastinum in cats: 45 cases (2000-2010).
AB  - OBJECTIVE: To characterize the incidence, etiology, presenting complaint,
      clinical course, and outcome of cats with pneumomediastinum. DESIGN:
      Retrospective study from the period of January 1st, 2000 to December 31st, 2010.
      SETTING: University teaching hospital. ANIMALS: Forty-five cats with a
      radiographic diagnosis of pneumomediastinum. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Medical and radiographic records were reviewed to identify cats
      with a radiographic diagnosis of pneumomediastinum. Clinical data were retrieved,
      including signalment, history, presenting clinical signs, diagnostic test
      results, treatment, complications, and survival to discharge. In 31 of 45 (69%)
      cats the pneumomediastinum was secondary to an obvious inciting cause. General
      anesthesia with endotracheal intubation and positive pressure ventilation was the
      most common cause in 17 of 45 (38%) cases. This was followed by trauma in 12 of
      45 (27%) cats, and tracheal foreign bodies in 2 of 45 (4%) cats. Spontaneous
      pneumomediastinum (unknown underlying cause) was diagnosed in 14 of 45 (31%) of
      cases. Onset of clinical signs and diagnosis of spontaneous pneumomediastinum was
      preceded by emesis in 6 of 14 cats. Common presenting signs were tachypnea seen
      in 27 of 45 (60%) cats, increased respiratory effort in 26 of 45 (58%) cats, and
      subcutaneous emphysema in 30 of 45 (66%) cats. Concurrent pneumothorax was
      identified in 21 of 45 (47%) cats, pleural effusion in 10 of 45 (22%), and
      pneumoretroperitoneum in 21 of 45 (47%). The mainstay of treatment was supportive
      care and treatment of the underlying disease process. The prognosis for recovery
      was good, with 87% survival until hospital discharge. CONCLUSIONS:
      Pneumomediastinum in cats is an infrequently diagnosed condition. It is often
      secondary to an event such as general anesthesia with endotracheal intubation and
      positive pressure ventilation but less frequently may occur spontaneously. The
      prognosis is good with appropriate supportive care.

PMID- 23855522
TI  - Time spatial labeling inversion pulse magnetic resonance angiography in pregnancy
      with adenomyosis.
AB  - Time spatial labeling inversion pulse (Time-SLIP) is a non-contrast magnetic
      resonance angiography (MRA) technique. No cases in which this technique was used
      during pregnancy have been reported. We report herein two cases with adenomyosis
      of the same size and location that underwent Time-SLIP MRA during pregnancy. In
      case 1, the blood flow within the adenomyosis was poor, and the uterine blood
      flow toward the placenta was normal, resulting in no fetal growth restriction
      (FGR). In case 2, the blood flow within the adenomyosis was quite rich, and
      placental blood flow seemed decreased, resulting in severe FGR. As well as the
      Doppler ultrasonography, Time-SLIP MRA was useful for evaluating uterine blood
      flow during pregnancy. This is the first report of the use of Time-SLIP MRA
      during pregnancy. 

PMID- 23855523
TI  - Biotransformation and bioconversion of phenolic compounds obtainment: an
      overview.
AB  - Phenolic compounds have recently been recognized for their influence on human
      metabolism, acting in the prevention of some chronic diseases as well as proving
      to be important antioxidants in food. Nevertheless, the extraction and
      concentration processes are usually carried out by organic solvent extraction
      from natural sources and can generate some drawbacks like phenolic compound
      degradation, lengthy process times and low yields. As a solution, some eco
      friendly technologies, including solid-state fermentation (SSF) or enzymatic
      assisted reaction, have been proposed as alternative processes. This article
      reviews the extraction of phenolic compounds from agro-industrial co-products by
      solid-state fermentation, even as friendly enzyme-assisted extractions. It also
      discusses the characteristics of each bioprocess system and the variables that
      affect product formation, as well as the range of substrates, microorganisms and
      enzymes that can be useful for the production of bioactive phenolic compounds.

PMID- 23855524
TI  - Health-related quality of life and social support among women treated for
      abortion complications in western Uganda.
AB  - BACKGROUND: While the impact of abortion complications on clinical outcomes and
      healthcare costs has been reported, we found no reports of their impact on Health
      Related Quality of Life (HRQoL), nor the role of social support in moderating
      such outcomes. In this study, we performed an assessment of the relationship
      between abortion complications, HRQoL and social support among women in Uganda.
      METHODS: We interviewed women who were discharged after treatment for abortion
      complications and, as a comparison, women visiting a regional referral hospital
      for routine obstetric care. We administered the EuroQol instrument and the Social
      Support Questionnaire Short-Form, and collected demographic and socioeconomic
      data. We performed descriptive analyses using t-tests, Wilcoxon rank-sum tests
      and chi-square tests, and multivariable linear regressions with interaction
      effects to examine the associations between abortion complications, EQ-5D utility
      scores and social support. RESULTS: Our study included 139 women (70 with
      abortion complications, and 69 receiving routine obstetric care). In four out of
      the 5 dimensions of the EQ-5D, a larger proportion of women with abortion
      complications reported "some or severe" problems than women receiving routine
      obstetric care (self-care: 42% v 24%, p=0.033; usual activities: 49% v 16%,
      p<0.001; pain/discomfort: 68% v 25%, p<0.001; and anxiety/depression: 60% v 22%,
      p<0.001). After adjusting for age, social support, wealth tertile, employment
      status, marital status, and HIV status, women with abortion complications had a
      0.12 (95% CI: 0.07, 0.18, p < 0.001) lower mean EQ-5D utility score than those
      receiving routine obstetric care. An analysis of the modifying effect of social
      support showed that a one-unit higher average number of people providing social
      support was associated with larger mean difference in EQ-5D utility score when
      comparing the two groups, while a one unit higher average satisfaction score with
      social support was associated with smaller mean differences in EQ-5D utility
      score. CONCLUSIONS: Our study suggests that abortion complications are associated
      with diminished HRQoL and the magnitude of the association depends on social
      support. However, the mediating role of social support in a setting of social and
      legal proscriptions to induced abortion is complex.

PMID- 23855525
TI  - Calibration is both functional and anatomical.
AB  - Bingham and Pagano (1998) described calibration as a mapping from embodied
      perceptual units to an embodied action unit and suggested that it is an inherent
      component of perception/action that yields accurate targeted actions. We tested
      two predictions of this "Mapping Theory." First, calibration should transfer
      between limbs, because it involves a mapping from perceptual units to an action
      unit, and thus is functionally specific to the action (Pan, Coats, and Bingham,
      2014). We used distorted haptic feedback to calibrate feedforward right hand
      reaches and tested right and left hand reaches after calibration. The calibration
      transferred. Second, the Mapping Theory predicts that limb specific calibration
      should be possible because the units are embodied and anatomy contributes to
      their scaling. Limbs must be calibrated to one another given potential anatomical
      differences among limbs. We used distorted haptic feedback to calibrate
      feedforward reaches with right and left arms simultaneously in opposite
      directions relative to a visually specified target. Reaches tested after
      calibration revealed reliable limb specific calibration. Both predictions were
      confirmed. This resolves a prevailing controversy as to whether calibration is
      functional (Bruggeman & Warren, 2010; Rieser, Pick, Ashmead, & Garing, 1995) or
      anatomical (Durgin et al., 2003; Durgin & Pelah, 1999). Necessarily, it is both.

PMID- 23855526
TI  - Topographic generalization of tactile perceptual learning.
AB  - Perceptual learning can improve our sensory abilities. Understanding its
      underlying mechanisms, in particular, when perceptual learning generalizes, has
      become a focus of research and controversy. Specifically, there is little
      consensus regarding the extent to which tactile perceptual learning generalizes
      across fingers. We measured tactile orientation discrimination abilities on 4
      fingers (index and middle fingers of both hands), using psychophysical measures,
      before and after 4 training sessions on 1 finger. Given the somatotopic
      organization of the hand representation in the somatosensory cortex, the
      topography of the cortical areas underlying tactile perceptual learning can be
      inferred from the pattern of generalization across fingers; only fingers sharing
      cortical representation with the trained finger ought to improve with it.
      Following training, performance improved not only for the trained finger but also
      for its adjacent and homologous fingers. Although these fingers were not exposed
      to training, they nevertheless demonstrated similar levels of learning as the
      trained finger. Conversely, the performance of the finger that was neither
      adjacent nor homologous to the trained finger was unaffected by training, despite
      the fact that our procedure was designed to enhance generalization, as described
      in recent visual perceptual learning research. This pattern of improved
      performance is compatible with previous reports of neuronal receptive fields
      (RFs) in the primary somatosensory cortex (SI) spanning adjacent and homologous
      digits. We conclude that perceptual learning rooted in low-level cortex can still
      generalize, and suggest potential applications for the neurorehabilitation of
      syndromes associated with maladaptive plasticity in SI.

PMID- 23855527
TI  - Concerns regarding BRAF testing algorithm.

PMID- 23855528
TI  - Multidirectional lip-closing force in adults with mandibular deviation.
AB  - The purpose of this study was to investigate the relationship between multidi
      rectional lip-closing force and facial soft tissue morphology in adults with
      mandibular deviation. Fifteen Japanese adults with mandibular deviation
      participated in this study. The deviation value was defined as the horizontal
      distance between soft tissue menton and the facial midline. The side of the soft
      tissue menton relative to the facial midline was defined as the deviated side and
      the opposite side as the non-deviated side. The signals of directional lip
      closing force (DLCF) were investigated in 8 directions. Total lip-closing force
      (TLCF) was calculated by adding DLCFs in 8 directions. Correlations and
      differences between the variables were analysed statistically. Significant
      positive correlations between TLCF and DLCFs were determined in six directions
      with the exception of the horizontal direction. Significant positive correlations
      for seven pairs of opposing DLCFs were found. The lower non-deviated DLCF was
      smaller than the three pairs of opposing lip-closing forces. Negative significant
      correlation was found between the deviation value and the upper deviated DLCF (P
      < 0.05). In individuals with mandibular deviation, lip-closing force in the lower
      non-deviated direction was found to be smaller than the opposing lip-closing
      forces. When mandibular deviation was greater, the upper deviated lip-closing
      force was smaller. 

PMID- 23855529
TI  - Usefulness of combined application of double-filtration plasmapheresis and twice
      daily injections of interferon-beta in hemodialysis patients with hepatitis C
      virus genotype 1b infection and a high viral load.
AB  - Hepatitis C virus (HCV) infection is common among hemodialysis (HD) patients and
      has been recognized as an important prognostic factor. Therefore, the aggressive
      antiviral therapy is necessary for HCV infection in HD patients. However, various
      treatment limitations exist in HD patients such as the inability to use
      ribavirin. We have previously reported that HCV RNA can be eradicated by
      administration of interferon (IFN)-beta during HD in patients with HCV infection
      caused by genotypes known to be sensitive to IFN therapy and low serum HCV RNA
      levels. In this case report, we tried to clarify the efficacy of combined
      application of double-filtration plasmapheresis (DFPP) and IFN-beta in HD
      patients with HCV genotype 1b infection and high serum HCV RNA levels. We report
      two HD patients with HCV genotype 1b infection and high viral loads who were
      successfully treated by five sessions of DFPP undertaken prior to treatment with
      IFN-beta (twice-daily injections for 2 weeks). HCV was eradicated by this
      combination therapy in both patients. We revealed the efficacy of combined
      application of DFPP and IFN-beta in HD patients with HCV genotype 1b infection
      and high serum HCV RNA levels. This combined therapy may be useful for the HD
      patients who are resistant to conventional IFN monotherapy. 

PMID- 23855530
TI  - Changes in the histological spectrum of glomerular diseases in the past 16 years
      in the North-Eastern region of Romania.
AB  - BACKGROUND: The aim of this study was to describe the findings of renal biopsies
      from a large nephrology center in Iasi, Romania, performed between 2005 and 2010.
      We compared these findings with our previous ones, from 1995 to 2004, as well as
      with similar reports. METHODS: We studied retrospectively 239 renal biopsies. The
      indications for renal biopsy were categorized into: nephrotic syndrome, acute
      nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and
      chronic kidney disease of unknown etiology. RESULTS: During the past 16 years, a
      gradual increase in the annual number of renal biopsies/per million population
      (p.m.p.)/year was observed, although this incidence remained lower than in other
      European countries. Nephrotic syndrome was the indication for renal biopsy in
      over 50% of cases. Glomerulonephritis (GN) was the main histological diagnosis in
      91% of cases, of which 56% were primary GN and 35% were secondary GN. The
      frequency of various types of primary GN was: membranoproliferative GN (MPGN) -
      29.3%, membranous nephropathy (MN) -27.5%, focal segmental glomerulosclerosis
      (FSGS) - 17.2%, mesangial GN (including IgAN) -13.7%, crescentic GN - 9.4%, and
      minimal change disease (MCD) - 2.5%. Compared to the previously reported period
      (1994-2004), we observed a significant decrease in the frequency of MPGN and
      significant increases in the frequency of FSGS and, particularly MN - which more
      than doubled. CONCLUSION: We report significant changes in the histological
      spectrum of GN in North-Eastern Romania in 2005-2010, compared to the previously
      reported 10-yrs. These changes seem to be following a trend that has also been
      observed in Western countries a few decades ago, and which may have a
      socioeconomic explanation.

PMID- 23855531
TI  - Global climate change and the evolutionary ecology of ecosystem functioning.
AB  - Environmental warming due to global climate change is an important stressor that
      stands to alter organismal physiology and, ultimately, carbon cycling in
      ecosystems. Yet the theoretical framework for predicting warming effects on whole
      ecosystem carbon balance by way of changes in organismal physiology remains
      rudimentary. This is because ecosystem science has yet to embrace principles of
      evolutionary ecology that offer the means to explain how environmental stress on
      organisms mediates ecosystem carbon dynamics. Here, using selected case studies
      and a theoretical model, I sketch out one framework that shows how increases in
      animal metabolic rates in response to thermal stress lead to phenotypically
      plastic shifts in animal elemental demand, from nitrogen-rich proteins that
      support production to carbon-rich soluble carbohydrates that support elevated
      energy demands. I further show how such a switch in resource selection alters the
      fate of carbon between atmospheric versus animal, plant, and soil pools. The
      framework shows that animals, despite having relatively low biomass
      representation in ecosystems, can nonetheless have disproportionately larger
      effects on carbon cycling in ecosystems whose effects are exacerbated by
      environmental stressors like climate warming. 

PMID- 23855533
TI  - Letter from the editor.

PMID- 23855534
TI  - Models of epistemic and ontological cognition: a new perspective of occupational
      therapy education.
AB  - Epistemic and ontological cognition (EOC) involve beliefs about knowledge and
      knowing. These include beliefs about the certainty and complexity of knowledge
      and the means of justifying knowledge, for example, through authority figures or
      personal experience. Research has shown that these beliefs can influence learning
      and achievement, and that they may be specific to a particular domain. The EOC
      that define a particular health profession and influence its production,
      acceptance, and use of knowledge have been termed practice epistemology. Despite
      the importance of its practice epistemology, little research has been done
      related to EOC in occupational therapy. This paper describes models of EOC as a
      basis for understanding their implications for occupational therapy epistemology,
      education, and practice.

PMID- 23855535
TI  - Teaching ill-structured problem solving using occupational therapy practice
      epistemology.
AB  - ABSTRACT Epistemic and ontological cognition (EOC) have to do with an
      individual's beliefs about knowledge and knowing. Research has shown that EOC
      have an influence on learning and achievement. EOC may be discipline-specific
      with a profession being defined by its practice epistemology. If an individual's
      EOC is inconsistent with the profession's practice epistemology, the student or
      practitioner may struggle with effectively solving ill-structured occupational
      performance problems. The purpose of this paper is to increase awareness of the
      constructs of EOC, to describe its importance to occupational therapy education
      and practice, and to provide recommendations for educators and researchers.
      Specific examples are detailed and recommendations for future research are
      proposed. 

PMID- 23855536
TI  - A framework for promoting scholarship productivity in occupational therapy
      curricula.
AB  - This paper describes a curricular model to support the production of quality
      research and development of occupational therapy professional students, prepared
      to become leaders in the production and utilization of evidence for practice.
      This model is designed for programs with faculty challenged by the dual mandate
      of program excellence and expectations for scholarly productivity needed for
      tenure and promotion: typically programs at research universities. The essence of
      the model is the paralleling of research and competencies for clinical practice
      where faculty and students participate as a community of scholars. It is based on
      the literature that addresses the tensions between achieving excellence in
      research and scholarly productivity, and excellence in teaching. The experience
      of one university with this model over a five-year period of time is shared with
      the student-faculty productivity outcomes. These outcomes include dissemination
      of 55 collaborative peer reviewed products and faculty has generated support for
      25 paid graduate assistantships. The combination of student outcomes and faculty
      support for their research has strengthened the ability of the faculty to excel
      in meeting the University mandate of scholarship while providing a high quality
      professional educational program.

PMID- 23855537
TI  - An experiential learning lab embedded in a didactic course: outcomes from a
      pediatric intervention course.
AB  - ABSTRACT This paper examines the outcomes of an experiential learning lab
      embedded in a didactic course. Program evaluation results were derived from
      student surveys and reflective journaling. The outcomes indicate that students
      valued the opportunity for experiential learning citing the primary benefits as
      the opportunity to, apply and manipulate knowledge, build clinical reasoning
      skills, and develop the professional skills to engage in and effectively manage
      an intervention session. 

PMID- 23855538
TI  - Client-chosen goals in occupational therapy: strategy and instrument pilot.
AB  - ABSTRACT Client-centered practice and outcomes research are missions of
      occupational therapy. Although strategies for client goal-setting have advanced
      the field, the process has limitations. This study tested a self-report strategy
      using brief, easy to score measures. The Goals for Occupational Therapy List was
      completed at mostly independent intake and paired with a follow-up measure of
      Goal Satisfaction Rating by 40 clients in an outpatient rehabilitation center.
      The strategy of pairing self-report measures of goal-setting and attainment was
      useful for clinicians and yielded important research findings. Application to
      occupational therapy and future research are suggested. 

PMID- 23855541
TI  - Cancer, stem cell misplacement and cancer stem cells.
AB  - The cell of origin of cancer as well as cancer stem cells is still a mystery. In
      a recent issue of JCMM, Wang et al. challenged the conventional somatic genetic
      mutation model of multi-stage carcinogenesis of breast cancer and proposed that
      'Invasive cancers are not necessary from preformed in situ tumours-an alternative
      way of carcinogenesis from misplaced stem cells'. If this stem cell misplacement
      theory could withstand future experimental evaluation, it may provide a paradigm
      shift in the prevention and management of cancer in the clinic. 

PMID- 23855542
TI  - Ready access to functionally embellished cis-hydrindanes and cis-decalins:
      protecting group-free total syntheses of (+/-)-Nootkatone and (+/-)
      Noreremophilane.
AB  - A simple and efficient synthesis of functionalized cis-hydrindanes and cis
      decalins was achieved using a sequential Diels-Alder/aldol approach in a highly
      diastereoselective manner. The scope of this method was tested with a variety of
      substrates and was successfully applied to the synthesis of two natural products
      in racemic form. The highlights of the present work provide ready access to 13
      new cis-hydrindanes/cis-decalins, a protecting group-free total synthesis of an
      insect repellent Nootkatone, and the first synthesis of a Noreremophilane using
      the shortest sequence. 

PMID- 23855543
TI  - Dynamic evolution of conducting nanofilament in resistive switching memories.
AB  - Resistive random access memory (ReRAM) has been considered the most promising
      next-generation nonvolatile memory. In recent years, the switching behavior has
      been widely reported, and understanding the switching mechanism can improve the
      stability and scalability of devices. We designed an innovative sample structure
      for in situ transmission electron microscopy (TEM) to observe the formation of
      conductive filaments in the Pt/ZnO/Pt structure in real time. The corresponding
      current-voltage measurements help us to understand the switching mechanism of ZnO
      film. In addition, high-resolution transmission electron microscopy (HRTEM) and
      electron energy loss spectroscopy (EELS) have been used to identify the atomic
      structure and components of the filament/disrupted region, determining that the
      conducting paths are caused by the conglomeration of zinc atoms. The behavior of
      resistive switching is due to the migration of oxygen ions, leading to
      transformation between Zn-dominated ZnO(1-x) and ZnO.

PMID- 23855544
TI  - Bleeding gastric hemolymphangioma: endoscopic therapy is feasible.

PMID- 23855545
TI  - Adjunctive therapy with intravenous lipid emulsion and methocarbamol for
      permethrin toxicity in 2 cats.
AB  - OBJECTIVE: To describe the use of an intravenous lipid emulsion (ILE) as an
      adjunctive therapy in 2 cats with permethrin toxicity. CASE SERIES SUMMARY: Two
      cats that presented with severe permethrin toxicity were treated with ILE as part
      of their treatment regimens. Both cats improved dramatically following therapy
      with decontamination, ILE, methocarbamol, and supportive care. NEW OR UNIQUE
      INFORMATION PROVIDED: This is the first reported use of ILE as an adjunctive
      treatment for cats with permethrin toxicity. Outcome was favorable in both cats
      and no adverse effects were noted from the ILE.

PMID- 23855546
TI  - Quercetin protects mouse brain against lead-induced neurotoxicity.
AB  - Quercetin (QE), the major bioflavonoid in the human diet, has been reported to
      have many benefits and medicinal properties. However, its protective effects
      against lead (Pb)-induced neurotoxicity have not been clarified. The aim of the
      present study was to investigate the effects of QE on neurotoxicity in mice
      exposed to Pb. Mice were exposed to lead acetate (20 mg/kg body weight/day)
      intragastrically with or without QE (15 and 30 mg/kg body weight/day)
      coadministration for 3 months. The data showed that QE significantly prevented Pb
      induced neurotoxicity in a dose-dependent manner. Exploration of the underlying
      mechanisms of QE action revealed that QE administration decreased Pb contents in
      blood (13.2, 19.1%) and brain (17.1, 20.0%). QE markedly increased NO production
      (39.1, 61.1%) and PKA activity (51.0, 57.8%) in brains of Pb-treated mice.
      Additionally, QE remarkably suppressed Pb-induced oxidative stress in mouse
      brain. Western blot analysis showed that QE increased the phosphorylations of
      Akt, CaMKII nNOS, eNOS, and CREB in brains of Pb-treated mice. The results
      suggest that QE can inhibit Pb-induced neurotoxicity and partly restore PKA, Akt,
      NOS, CaMKII, and CREB activities. 

PMID- 23855547
TI  - Attempting to answer a meaningful question enhances subsequent learning even when
      feedback is delayed.
AB  - Attempting to retrieve information from memory enhances subsequent learning even
      if the retrieval attempt is unsuccessful. Recent evidence suggests that this
      benefit materializes only if subsequent study occurs immediately after the
      retrieval attempt. Previous studies have prompted retrieval using a cue (e.g.,
      whale-???) that has no intrinsic answer. Experiment 1 replicated prior word pair
      studies, but in Experiment 2, when participants learned meaningful trivia
      questions, testing enhanced learning even when subsequent study was delayed. Even
      in Experiment 3, when subsequent study was delayed by up to 24 hr, tests enhanced
      learning on a final test another 24 hr later. These findings may give comfort to
      educators who worry that asking a question or giving a test, on which students
      inevitably make mistakes, impairs learning if feedback is not immediate. They
      also suggest that there is a consensus in the literature thus far: Questions with
      rich semantic content enhance subsequent learning even when feedback is delayed,
      but less meaningful questions without an intrinsic answer enhance learning only
      when feedback is immediate. (PsycINFO Database Record (c) 2013 APA, all rights
      reserved). 

PMID- 23855548
TI  - Focusing the search: proactive and retroactive interference and the dynamics of
      free recall.
AB  - Targeting information in long-term memory is an important cognitive ability, but
      one that is not well understood. In this study, 4 experiments were conducted to
      examine the influence of proactive and retroactive interference on memory
      targeting. Participants were given either 1 or 2 lists and asked to recall List
      1, List 2, or in some cases both lists. Multiple dependent measures were explored
      including the proportion of items recalled, number of intrusions output, and
      recall latency to arbitrate between 4 extant accounts of memory targeting. In
      general, recalling either List 1 or List 2 resulted in lower probability of
      recall, recall of more intrusions, and longer recall latencies compared to when
      recalling a list alone, suggesting both proactive and retroactive interference.
      These results suggest that long-term memory targeting is guided by noisy temporal
      contextual cues (unless other salient cues are present) that activate both
      relevant and irrelevant memoranda that are then subjected to a postretrieval
      monitoring process.

PMID- 23855549
TI  - Learned predictiveness influences rapid attentional capture: evidence from the
      dot probe task.
AB  - Attentional theories of associative learning and categorization propose that
      learning about the predictiveness of a stimulus influences the amount of
      attention that is paid to that stimulus. Three experiments tested this idea by
      looking at the extent to which stimuli that had previously been experienced as
      predictive or nonpredictive in a categorization task were able to capture
      attention in a dot probe task. Consistent with certain attentional theories of
      learning, responses to the dot probe were faster when it appeared in a location
      cued by a predictive stimulus compared to a location cued by a nonpredictive
      stimulus. This result was obtained only with short (250-ms or 350-ms) but not
      long (1,000-ms) delays between onset of the stimuli and the dot probe, suggesting
      that the observed spatial cuing effect reflects the operation of a relatively
      rapid, automatic process. These findings are consistent with the approach to the
      relationship between attention and learning taken by the class of models
      exemplified by Mackintosh's (1975) theory.

PMID- 23855550
TI  - The shape of things to come: evaluating word frequency as a continuous variable
      in recognition memory.
AB  - The role of experience in memory, specifically the word frequency (WF) mirror
      effect showing higher hit rates and lower false alarm rates for low-frequency
      words, is one of the hallmarks of memory. However, this "regularity of memory" is
      limited because normative WF has been treated as discrete (low vs. high). We
      evaluate the extent to which the prototypical WF mirror effect holds when WF is
      treated as a continuous variable. We find a clear nonmonotonic U-shaped
      relationship. Hit rates are higher for both low-frequency and high-frequency
      words. Linear and quadratic regression models were fit to the data at both the
      item and the participant level, and the quadratic model provided a better fit at
      both levels. This finding is inconsistent with the empirical and theoretical
      finding of a mirror effect and requires a novel approach to accounting for the
      role of experience in episodic memory.

PMID- 23855551
TI  - Reading aloud: does previous trial history modulate the joint effects of stimulus
      quality and word frequency?
AB  - No one would argue with the proposition that how we process events in the world
      is strongly affected by our experience. Nonetheless, recent experience (e.g.,
      from the previous trial) is typically not considered in the analysis of timed
      cognitive performance in the laboratory. Masson and Kliegl (2013) reported that,
      in the context of the lexical decision task, the nature of the previous trial
      strongly modulates the joint effects of word frequency and stimulus quality-a
      joint effect that is widely reported to be additive when averaged over trial
      history. In particular, their analysis suggests there may be no genuine
      additivity of these factors. Here we extended this line of investigation by
      reanalyzing data reported by O'Malley and Besner (2008) in which subjects read
      words and nonwords aloud, with word frequency and stimulus quality as manipulated
      factors. These factors are additive on reaction time in the standard analysis of
      variance. Contrary to Masson and Kliegl's finding for lexical decision, when
      previous trial history is taken into consideration, these 2 factors still do not
      interact. This suggests that, at least in the context of reading aloud, previous
      trial does not modulate how the effects of these 2 factors combine. Some
      implications are briefly noted.

PMID- 23855552
TI  - Effect of interleukin-6 receptor blockade on feto-maternal outcomes in a rat
      model of intrauterine inflammation.
AB  - AIM: To study the effect of blocking the inflammatory cascade with interleukin-6
      receptor antibody (anti-IL-6R) on feto-maternal outcomes in a rat model. METHODS:
      Pregnant Sprague-Dawley rats (n = 38) were injected intraperitoneally (day 22)
      (control, anti-IL-6R 30 MUg/kg, lipopolysaccharide [LPS] 250 MUg/kg or 500 MUg/kg
      alone or combined with anti-IL-6R) followed by preterm caesarian performed 12 h
      later. Resuscitated pups (n = 179) were given to surrogate mothers. Primary
      outcomes were maternal and pup mortality. RESULTS: Fifty percent of pregnant rats
      died after LPS 500 MUg/kg + anti-IL-6R injection but none in other groups.
      Neonatal mortality at 24 h was 63% and 86% in LPS 500 MUg/kg and LPS 500 MUg/kg +
      anti-IL-6R groups, respectively (P < 0.05). Surviving pups in the latter group
      presented a severe growth deficit compared to the LPS 500 MUg/kg group (P < 0.01)
      and showed no difference with controls for open field testing. Maternal cytokine
      analysis after LPS 500 MUg/kg + anti-IL-6R injection showed a tendency for
      increased IL-1 production (P = 0.06). CONCLUSION: Paradoxically, the association
      of pregnancy, inflammation and anti-IL-6R increases the inflammatory effects of
      LPS.

PMID- 23855553
TI  - Induced sputum levels of IL-33 and soluble ST2 in young asthmatic children.
AB  - OBJECTIVE: Interleukin-33 is an IL-1 family cytokine which signals via its T1/ST2
      receptor, and acts as a key regulator of inflammation, notably the type-2
      response implicated in asthma. This study aims to measure the expression of
      soluble ST2 (sST2) and IL-33 in asthmatic children, depending on disease
      activity. METHODS: Thirty-seven children with well-defined asthma (20 moderate
      and 17 mild asthmatics) were studied. IL-33 and sST2 were measured by ELISA in
      serum and induced sputum (IS) samples, and compared with 22 age- and sex-matched
      healthy controls. Real-time quantitative PCR was used to determine IL-33 and TNF
      alpha mRNA expression in IS. RESULTS: sST2 and IL-33 levels in IS and serum were
      significantly higher in patients compared with healthy controls (p = 0.0001). The
      increase in sST2 and IL33 was significantly more important in moderate cases than
      in mild asthma. A significant correlation was observed between serum and IS IL-33
      levels (r = 0.497; p = 0.0018). Higher levels of IL-33 mRNA were detected in IS
      from asthmatics than those observed in controls. A significant correlation was
      found between TNF-alpha and IL-33 mRNA expression in the asthmatic subjects (r =
      0.772, p = 0.0001). CONCLUSIONS: Values of sST2 and IL-33 observed in IS were
      found to correlate with disease activity. Elevated IL-33 mRNA expression in IS
      and its correlation with TNF-alpha reflected the inflammatory process observed in
      the lung of young asthmatics.

PMID- 23855554
TI  - Programs as causal models: speculations on mental programs and mental
      representation.
AB  - Judea Pearl has argued that counterfactuals and causality are central to
      intelligence, whether natural or artificial, and has helped create a rich
      mathematical and computational framework for formally analyzing causality. Here,
      we draw out connections between these notions and various current issues in
      cognitive science, including the nature of mental "programs" and mental
      representation. We argue that programs (consisting of algorithms and data
      structures) have a causal (counterfactual-supporting) structure; these
      counterfactuals can reveal the nature of mental representations. Programs can
      also provide a causal model of the external world. Such models are, we suggest,
      ubiquitous in perception, cognition, and language processing. 

PMID- 23855555
TI  - Hip fracture risk assessment: artificial neural network outperforms conditional
      logistic regression in an age- and sex-matched case control study.
AB  - BACKGROUND: Osteoporotic hip fractures with a significant morbidity and excess
      mortality among the elderly have imposed huge health and economic burdens on
      societies worldwide. In this age- and sex-matched case control study, we examined
      the risk factors of hip fractures and assessed the fracture risk by conditional
      logistic regression (CLR) and ensemble artificial neural network (ANN). The
      performances of these two classifiers were compared. METHODS: The study
      population consisted of 217 pairs (149 women and 68 men) of fractures and
      controls with an age older than 60 years. All the participants were interviewed
      with the same standardized questionnaire including questions on 66 risk factors
      in 12 categories. Univariate CLR analysis was initially conducted to examine the
      unadjusted odds ratio of all potential risk factors. The significant risk factors
      were then tested by multivariate analyses. For fracture risk assessment, the
      participants were randomly divided into modeling and testing datasets for 10-fold
      cross validation analyses. The predicting models built by CLR and ANN in modeling
      datasets were applied to testing datasets for generalization study. The
      performances, including discrimination and calibration, were compared with non
      parametric Wilcoxon tests. RESULTS: In univariate CLR analyses, 16 variables
      achieved significant level, and six of them remained significant in multivariate
      analyses, including low T score, low BMI, low MMSE score, milk intake, walking
      difficulty, and significant fall at home. For discrimination, ANN outperformed
      CLR in both 16- and 6-variable analyses in modeling and testing datasets
      (p?<?0.005). For calibration, ANN outperformed CLR only in 16-variable analyses
      in modeling and testing datasets (p?=?0.013 and 0.047, respectively).
      CONCLUSIONS: The risk factors of hip fracture are more personal than
      environmental. With adequate model construction, ANN may outperform CLR in both
      discrimination and calibration. ANN seems to have not been developed to its full
      potential and efforts should be made to improve its performance.

PMID- 23855556
TI  - Concerns regarding BRAF testing algorithm: reply from authors.

PMID- 23855557
TI  - The effect of tongue position and resulting vertical dimension on masticatory
      muscle activity. A cross-sectional study.
AB  - The purpose of this study was to: (a) compare the tonic electromyographic (EMG)
      activity of the temporalis and masseter muscles between two tongue positions, (b)
      compare the vertical dimension (VD) resulting from each tongue position and (c)
      determine the influence of the VD on the tonic EMG activity for each tongue
      position. Thirty-three healthy dental students with natural dentition and
      bilateral molar support, between the ages of 18 and 22 years, with no prior
      history of oro-facial injury, or current or past pain in the jaw, mouth, or
      tongue participated in the study. Tonic masseteric and temporalis EMG activities
      were recorded using surface electrodes. Subjects were instructed to passively
      place the tongue either on the anterior hard palate or in the floor of the mouth.
      At each tongue position, the resulting EMG and VD were recorded. No significant
      difference in EMG activity was found for either the masseter (P-value = 0.5376)
      or temporalis muscle (P-value = 0.7410), between the two tongue positions.
      However, there was a significant difference in the VD resulting from the two
      different tongue positions, being greater with the tongue placed in the floor of
      the mouth. There was no statistically significant correlation between VD and EMG
      activity for both tongue positions. In spite of the lack of difference in the
      effect of both tongue positions on the masseteric and temporalis EMG activity, an
      increment of the VD was registered for the floor of mouth-tongue position.
      However, VD was not correlated with EMG activity for both tongue positions.

PMID- 23855558
TI  - Using the Bayesian Improved Surname Geocoding Method (BISG) to create a working
      classification of race and ethnicity in a diverse managed care population: a
      validation study.
AB  - OBJECTIVE: To validate classification of race/ethnicity based on the Bayesian
      Improved Surname Geocoding method (BISG) and assess variations in validity by
      gender and age. DATA SOURCES/STUDY SETTING: Secondary data on members of Kaiser
      Permanente Georgia, an integrated managed care organization, through 2010. STUDY
      DESIGN: For 191,494 members with self-reported race/ethnicity, probabilities for
      belonging to each of six race/ethnicity categories predicted from the BISG
      algorithm were used to assign individuals to a race/ethnicity category over a
      range of cutoffs greater than a probability of 0.50. Overall as well as gender-
      and age-stratified sensitivity, specificity, positive predictive value (PPV), and
      negative predictive value (NPV) were calculated. Receiver operating
      characteristic (ROC) curves were generated and used to identify optimal cutoffs
      for race/ethnicity assignment. PRINCIPAL FINDINGS: The overall cutoffs for
      assignment that optimized sensitivity and specificity ranged from 0.50 to 0.57
      for the four main racial/ethnic categories (White, Black, Asian/Pacific Islander,
      Hispanic). Corresponding sensitivity, specificity, PPV, and NPV ranged from 64.4
      to 81.4 percent, 80.8 to 99.7 percent, 75.0 to 91.6 percent, and 79.4 to 98.0
      percent, respectively. Accuracy of assignment was better among males and
      individuals of 65 years or older. CONCLUSIONS: BISG may be useful for classifying
      race/ethnicity of health plan members when needed for health care studies.

PMID- 23855559
TI  - Sensitive detection of protein kinase A activity in cell lysates by peptide
      microarray-based assay.
AB  - In the present work, the activities of protein kinase A (PKA) in cell lysates
      have been detected by a peptide microarray-based resonance light scattering assay
      with gold nanoparticle probes. Highly sensitive detection of PKA activity in 0.1
      MUg total cell proteins of SHG-44 cell lysate (corresponding to 200 cells) is
      achieved by a selected peptide substrate. The experimental results also
      demonstrate that the assay can be employed to evaluate expression levels of PKA
      activity in different cell lines and chemical (e.g., Forskolin )-mediated PKA
      activity fluctuation in living cells. In addition, PKA inhibition by the
      inhibitor (H89) is shown, suggesting the potential for screening PKA inhibitors
      at the living cell level. 

PMID- 23855561
TI  - Immunization against recombinant GnRH-I alters ultrastructure of gonadotropin
      cell in an experimental boar model.
AB  - BACKGROUND: Gonadotropin cell is the main responsible for the secretion of
      follicle stimulating hormone (FSH) and luteinizing hormone (LH), and
      immunocastration reduces the concentrations of serum FSH and LH. A few studies
      have reported the histological structure of gonadotropin cells obtained from
      immunocastration animals at the light microscopy level. However, the
      ultrastructure of gonadotropin cells remains largely unexplored. The aim of this
      study was to evaluate and to compare ultrastructure of gonadotropin cell in
      gonadally intact boars and immunologically castrated male animals. FINDINGS: In
      this study, serum and adenohypophysis tissue were collected from nine gonadally
      intact boars and nine male pigs treated with recombinant gonadotropin releasing
      hormone I (GnRH-I). Anti-GnRH-I antibodies in serum and the ultrastructure of
      gonadotropin cell in adenohypophysis were determined by enzymelinked
      immunosorbent assay and electron microscopy, respectively. The results
      demonstrated that active immunization against recombinant GnRH-I increased serum
      GnRH-I antibody levels (P<0.05). Ultramicroscopic analysis of gonadotropin cell
      revealed a decrease (P<0.05) in the number and size of the large granules and
      small granules in the recombinant GnRH-I immunized animals. CONCLUSIONS: We
      conclude that immunization against recombinant GnRH-I induces severe atrophy of
      granules in gonadotropin cell of boars, possibly reflecting GnRH-I regulation of
      gonadotropin cell.

PMID- 23855562
TI  - Characteristics and prediction of hepatitis B e-antigen negative hepatitis
      following seroconversion in patients with chronic hepatitis B.
AB  - AIM: We analyzed the characteristics of alanine aminotransferase (ALT)
      abnormality after achieving hepatitis B e-antigen (HBeAg) seroconversion (SC) and
      other factors associated with the occurrence of HBeAg negative hepatitis.
      METHODS: We followed 36 patients with chronic hepatitis B from 3 years prior to
      at least 3 years after SC (mean, 11.6 years) and examined ALT, hepatitis B virus
      (HBV) DNA, HB surface antigen, HB core-related antigen (HBcrAg) levels and
      mutations related to HBeAg SC. RESULTS: ALT normalization (<31 IU/L for at least
      1 year) was primarily observed until 2 years following SC, after which it became
      more infrequent. We next divided patients into abnormal (>=31 IU/L, n = 20) and
      normal (<31 IU/L, n = 16) groups based on integrated ALT level after the time
      point of 2 years from SC, and considered the former group as having HBeAg
      negative hepatitis in the present study. Although changes in median levels of ALT
      and HBcrAg differed significantly between the groups, multivariate analysis
      showed ALT normalization within 2 years after SC to be the only significant
      determining factor for this disease (P = 0.001). We then assessed the 19 patients
      whose ALT was normal at 2 years following SC, four of whom developed HBeAg
      negative hepatitis. Increased levels of HBV DNA (P = 0.037) and HBcrAg (P =
      0.033) were significant factors of potential relevance. CONCLUSION: ALT
      abnormality after 2 years of SC may be evaluated as HBeAg-negative hepatitis.
      ALT, HBV DNA and HBcrAg levels may be useful in predicting the outcome of
      patients who achieve HBeAg SC.

PMID- 23855564
TI  - The development of mental scenario building and episodic foresight.
AB  - Episodic foresight is the future-directed counterpart of episodic memory. It is a
      sophisticated, potentially uniquely human capacity, with tremendous adaptive
      consequences. Here we review what is currently known about its development
      through early childhood. We tackle this from two distinct perspectives. First, we
      present the first systematic evaluation of the development of purported
      components of mental scenario building as highlighted by a theater metaphor: the
      stage, the playwright, the set, the actors, the director, the executive producer,
      and the broadcaster. We find that, although there are diverse developmental
      trajectories, by 4 years of age children have acquired the basic cognitive
      components required to mentally construct specific future events. Second, we
      examine recent attempts to test children's episodic foresight more directly and
      find that results are in line with those examining the development of required
      components. This is not to say that children younger than four have no inkling of
      upcoming events or that older children have nothing left to learn about
      constructing the future. Episodic foresight, and its neurocognitive foundations,
      continues to develop throughout childhood. 

PMID- 23855566
TI  - Special issue of obesity and the role of occupational therapy.

PMID- 23855565
TI  - Plasma and synovial fluid concentration of doxycycline following low-dose, low
      frequency administration, and resultant inhibition of matrix metalloproteinase-13
      from interleukin-stimulated equine synoviocytes.
AB  - REASONS FOR STUDY: To determine whether low-dose, low-frequency doxycycline
      administration is capable of achieving chondroprotective concentrations within
      synovial fluid (SF) while remaining below minimum inhibitory concentration 90
      (MIC90 ) of most equine pathogens and would be an option in the management of
      osteoarthritis. OBJECTIVES: To determine whether low-dose, low-frequency oral
      administration of doxycycline can attain in vivo SF concentrations capable of
      chondroprotective effects through reduction of matrix metalloproteinase (MMP)-13
      activity, while remaining below MIC90 of most equine pathogens. STUDY DESIGN:
      Descriptive pharmacokinetic study with crossover design. METHODS: Two groups of 6
      horses received oral doxycycline. Plasma and SF doxycycline concentrations were
      measured using high performance liquid chromatography. Group 1 received 5 mg/kg
      bwt q. 24 h with 21 blood and 8 SF samples collected over 120 h; Group 2 received
      5 mg/kg bwt q. 48 h with 27 blood and 11 SF samples collected over 192 h.
      Cultured synoviocytes were treated with interleukin-1alpha (1 ng/ml) for 24 h to
      stimulate MMP synthesis, and then SF was added to the culture medium for 96 h.
      MMP-13 protein and mRNA were measured in synoviocyte culture medium and
      synoviocytes, respectively. RESULTS: Mean doxycycline concentration >=0.043
      MUg/ml (previously demonstrated to inhibit MMP-13) was achieved in plasma by t =
      0.25 h and SF by t = 48 h in Group 1, and in plasma by t = 0.17 h and SF by t = 1
      h in Group 2. Synoviocyte culture medium containing doxycycline from Groups 1 and
      2 had significantly decreased active MMP-13 protein concentration, and
      synoviocytes cultured in this medium had significantly decreased MMP-13 gene
      expression compared to controls. Plasma doxycycline concentration in both groups
      and SF doxycycline concentration in Group 2 demonstrated a cumulative effect.
      CONCLUSIONS: Low-dose orally administered doxycycline achieves SF concentrations
      in vivo capable of diminishing MMP-13 expression. This study supports the use of
      doxycycline as a disease modifying osteoarthritic drug.

PMID- 23855567
TI  - Obesity, health and quality of life: a conversation to further the vision in
      occupational therapy.
AB  - Occupational therapy is one of the most powerful professions to support the
      development of healthy lifestyles, promote health and well-being and empower
      individuals, communities and populations, especially those impacted by or at risk
      for obesity. Development of healthy lifestyles enhances and promotes quality of
      life. This article discusses the need for occupational therapy professionals to
      explore the many possibilities that enable lifestyle change for people at risk
      for or who are obese or overweight. Embracing and integrating health promotion
      and wellness into everyday practice, particularly for those impacted by obesity,
      is emphasized.

PMID- 23855568
TI  - A multi-tiered approach to addressing the mental health issues surrounding
      obesity in children and youth.
AB  - Obesity in children and youth is a major public health concern known to have a
      significant impact on physical and mental health. Although traditional approaches
      to obesity have emphasized diet and exercise at the individual level, broader
      attention to the mental health consequences of obesity is crucial. Individuals
      who are obese live in a world where they are often less accepted resulting in
      social exclusion and discrimination. A public health multi-tiered approach to
      obesity focusing on mental health promotion, prevention, and individualized
      intervention is presented.

PMID- 23855560
TI  - Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a
      randomised controlled trial of low versus standard dialysate sodium concentration
      during hemodialysis for regression of left ventricular mass.
AB  - BACKGROUND: The current literature recognises that left ventricular hypertrophy
      makes a key contribution to the high rate of premature cardiovascular mortality
      in dialysis patients. Determining how we might intervene to ameliorate left
      ventricular hypertrophy in dialysis populations has become a research priority.
      Reducing sodium exposure through lower dialysate sodium may be a promising
      intervention in this regard. However there is clinical equipoise around this
      intervention because the benefit has not yet been demonstrated in a robust
      prospective clinical trial, and several observational studies have suggested
      sodium lowering interventions may be deleterious in some dialysis patients.
      METHODS/DESIGN: The Sodium Lowering in Dialysate (SoLID) study is funded by the
      Health Research Council of New Zealand. It is a multi-centre, prospective,
      randomised, single-blind (outcomes assessor), controlled parallel assignment 3
      year clinical trial. The SoLID study is designed to study what impact low
      dialysate sodium has upon cardiovascular risk in dialysis patients. The study
      intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over
      24 months and follow up each participant over 12 months. Key exclusion criteria
      are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis
      serum sodium of <135 mM, and maintenance hemodiafiltration. In addition, some
      medical conditions, treatments or participation in other dialysis trials, which
      contraindicate the SoLID study intervention or confound its effects, will be
      exclusion criteria. The intervention and control groups will be dialysed using
      dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary
      outcome measure is left ventricular mass index, as measured by cardiac magnetic
      resonance imaging, after 12 months of intervention. Eleven or more secondary
      outcomes will be studied in an attempt to better understand the physiologic and
      clinical mechanisms by which lower dialysate sodium alters the primary end point.
      DISCUSSION: The SoLID study is designed to clarify the effect of low dialysate
      sodium upon the cardiovascular outcomes of dialysis patients. The study results
      will provide much needed information about the efficacy of a cost effective,
      economically sustainable solution to a condition which is curtailing the lives of
      so many dialysis patients. TRIAL REGISTRATION: Australian and New Zealand
      Clinical Trials Registry number: ACTRN12611000975998.

PMID- 23855569
TI  - Childhood obesity: effects on children's participation, mental health, and
      psychosocial development.
AB  - Obesity and being overweight in a child significantly affects his or her healthy
      development hence there is an understandable focus in the occupational therapy
      literature on the physical health and difficulties in motor function related to
      obesity. However, this emphasis somewhat overshadows the psychosocial issues of
      growing-up obese or overweight. The objective of this paper is to apprise readers
      of the salient multiple psychosocial sequelae associated with childhood obesity
      including weight bias and victimization. A conceptual systems framework that
      supports a multifaceted approach to the occupational and developmental challenges
      on a population and/or individual level is discussed.

PMID- 23855571
TI  - Cross-border contributions to obesity research and interventions: a review of
      Canadian and American occupational therapy contributions.
AB  - This paper identifies the contributions of Canadian and American occupational
      therapists to the empirical discourse on obesity. This scoping study includes an
      independent review of the published literature followed by a series of meetings
      during which key themes and contributions were categorized. The Person,
      Environment, Occupation, and Performance Model (Baum & Christiansen, 2005) was
      used to organize the themes reported in the literature. Although occupational
      therapists contribute to knowledge about body systems and functions as well as
      activity limitations and participation restrictions for persons with obesity, the
      majority of work has a focus on the environment and the person, with limited
      attention to occupation. Occupational therapy practitioners and researchers are
      contributing in areas valued in obesity research and practice but can do more to
      promote consideration of the interaction of personal, environmental, and
      occupational factors which may cause obesity or contribute to the participation
      in everyday living for persons with obesity.

PMID- 23855570
TI  - Culturally competent interventions to address obesity among African American and
      Latino children and youth.
AB  - While obesity impacts all ethnic groups in the United States, African Americans
      and Latinos are particularly at high risk for obesity. The purpose of this paper
      is to provide an analysis of the literature on evidence-based culturally
      competent strategies for addressing and preventing obesity and discuss roles for
      occupational therapists working with populations at risk for obesity in the
      school or therapeutic clinical environment. A review was conducted of over 80
      research articles describing successful interventions conducted in schools and
      communities targeting African Americans and Latino children. Although unique
      single strategies are highlighted in this paper, obesity interventions are
      complex and involved a number of multilevel strategies. The results of the
      analysis of the literature are presented according to strategies that promote
      healthy eating, physical activity, and overall healthy lifestyles. Along with the
      cultural competent strategies, we recommend specific roles for occupational
      therapists in order to promote the implementation of each particular strategy.
      Lastly, implications for occupational therapy are discussed.

PMID- 23855572
TI  - Service learning in a pediatric weight management program to address childhood
      obesity.
AB  - This paper describes an inter-professional service learning collaboration and
      reflects benefits and considerations when incorporating a family-oriented
      approach in the community-based pediatric weight management program. Because
      obesity has tremendous consequences on a nation's health and economy, a
      pediatrician in a community health network has utilized an inter-professional
      team to implement a pediatric weight management program targeting children
      between the ages of 8 and 15 years. The team incorporates a culturally sensitive
      curriculum using a family-oriented approach for obesity prevention and
      intervention. Physicians, registered dietitians, occupational therapists, nurse
      practitioners, and mental health professionals assist participants in adopting a
      healthier lifestyle by addressing physical and psychosocial issues related to
      obesity, developing a nutrition plan, making healthier food choices, and finding
      fun ways to be more physically active. Graduate occupational therapy students
      work closely with the team members to assist delivery of interactive activities
      and behavior intervention.

PMID- 23855573
TI  - Effects of an occupation-based obesity prevention program for children at risk.
AB  - Since the prevalence of obesity-related medical conditions in children and
      adolescents has increased over the past several years obesity prevention has
      become a vital need for our society and a focus of our professional practice. The
      primary aim of this pilot study was to increase children's experiences with
      physical activity and healthy foods to promote self-efficacy related to a healthy
      lifestyle. Using a pre- and posttest design, the Healthy Choices for Me program
      was evaluated for its efficacy. Intervention consisted of a 12-week after-school
      program implemented by occupational therapy students. Elementary-aged children
      from two lower social economic schools in an urban area participated in the
      program. Results demonstrated positive changes in food behavior, food self
      efficacy, and vegetable consumption for the participants.

PMID- 23855575
TI  - Welcome to the second instructional insight column!

PMID- 23855576
TI  - Instructional insight into interprofessional education (IPE).
AB  - Working with other health science professionals in order to promote positive
      client outcomes is common practice in many rehabilitation delivery areas. The
      evolution of health care delivery seems to expect more efficient and cost
      effective client care, therefore the introduction of blended professional teams
      is moving to the forefront of professional education. As such, providing
      opportunities to health science students to experience the roles and practice of
      other professions during the academic portion of their education,
      Interprofessional Education (IPE), has become and expectation of accrediting
      bodies. The Accreditation Council for Occupational Therapy Education (ACOTE) has
      included standards related to IPE (ACOTE, 2012). The most recent ACOTE standards,
      effective July 2013, require occupational therapy educators to provide
      interprofessional collaborative situations to increase student awareness of and
      participation in interprofessional learning (ACOTE, 2012). This article describes
      some of the IPE experiences of one small university as well as provides
      suggestion for other occupational therapy educational programs to move forward to
      meeting the newly established accreditation standards.

PMID- 23855584
TI  - Comment on 'Predicting treatment response in psoriasis using serum levels of
      adalimumab and etanercept: a single-centre, cohort study'.

PMID- 23855585
TI  - Multicomponent chemical imaging of pharmaceutical solid dosage forms with
      broadband CARS microscopy.
AB  - We compare a coherent Raman imaging modality, broadband coherent anti-Stokes
      Raman scattering (BCARS) microscopy, with spontaneous Raman microscopy for
      quantitative and qualitative assessment of multicomponent pharmaceuticals.
      Indomethacin was used as a model active pharmaceutical ingredient (API) and was
      analyzed in a tabulated solid dosage form, embedded within commonly used
      excipients. In comparison with wide-field spontaneous Raman chemical imaging,
      BCARS acquired images 10* faster, at higher spatiochemical resolution and with
      spectra of much higher SNR, eliminating the need for multivariate methods to
      identify chemical components. The significant increase in spatiochemical
      resolution allowed identification of an unanticipated API phase that was missed
      by the spontaneous wide-field method and bulk Raman spectroscopy. We confirmed
      the presence of the unanticipated API phase using confocal spontaneous Raman,
      which provided spatiochemical resolution similar to BCARS but at 100* slower
      acquisition times. 

PMID- 23855586
TI  - Effects of sulfur fertilization on the accumulation of health-promoting
      phytochemicals in radish sprouts.
AB  - The effects of sulfur fertilization on the growth profile, the contents of
      glucosinolates, anthocyanins, vitamin C, carotenoids, chlorophylls, total
      phenolics, and the FRAP value in radish seeds and sprouts were investigated. The
      concentrations of glucosinolates and antioxidants in sprouts were strongly
      influenced by the process of germination. Sulfur fertilization induced
      significant increases in the contents of individual glucosinolates, carotenoids,
      chlorophylls, and total phenolics. The phenolic contents in sprouts cultivated
      using 20, 60, or 100 mg/L sulfate were 20.7%, 40.4%, and 40.8% higher,
      respectively, than those of 7-day-old control sprouts. No detectable effects were
      observed on the contents of 4-methoxy-glucobrassicin and vitamin C. In addition,
      the accumulation of anthocyanins in 7-day-old sprouts decreased by 14.8-39.3%
      upon sulfur fertilization. These findings indicated that the application of
      sulfur fertilization has the potential to enhance the levels of health-promoting
      compounds in radish sprouts. 

PMID- 23855588
TI  - Novel mutation (p.L91P, c.272T>C) of keratin 17 in a case with pachyonychia
      congenita type 2.

PMID- 23855589
TI  - Tandem Suzuki-Miyaura coupling/acid-catalyzed cyclization between vinyl ether
      boronates and vinyl halides: a concise approach to polysubstituted furans.
AB  - Polysubstituted 2-(omega-hydroxyalkyl)furans were prepared by tandem Suzuki
      Miyaura coupling/acid-catalyzed cyclization starting from appropriately
      substituted 3-haloallylic alcohols and dihydrofuran-, dihydropyran- or glycal
      derived pinacol boronates. 

PMID- 23855587
TI  - Reversing endogenous alloreactive B cell GC responses with anti-CD154 or CTLA
      4Ig.
AB  - Alloantibodies mediate acute antibody-mediated rejection as well as chronic
      allograft rejection in clinical transplantation. To better understand the
      cellular dynamics driving antibody production, we focused on the activation and
      differentiation of alloreactive B cells in the draining lymph nodes and spleen
      following sensitization to allogeneic cells or hearts. We used a modified
      staining approach with a single MHC Class I tetramer (K(d)) bound to two
      different fluorochromes to discriminate between the Class I-binding and
      fluorochrome-streptavidin-binding B cells with a high degree of specificity and
      binding efficiency. By Day 7-8 postsensitization, there was a 1.5- to 3.2-fold
      increase in the total numbers of K(d) -binding B cells. Within this K(d) -binding
      B cell population, approximately half were IgD(low) , MHC Class II(high) and
      CD86(+), 30-45% expressed a germinal center (Fas(+) GL7(+)) phenotype and 3-12%
      were IRF4(hi) plasma cells. Remarkably, blockade with anti-CD40 or CTLA-4Ig,
      starting on Day 7 postimmunization for 1 or 4 weeks, completely dissolved
      established GCs and halted further development of the alloantibody response. Thus
      MHC Class I tetramers can specifically track the in vivo fate of endogenous,
      Class I-specific B cells and was used to demonstrate the ability of delayed
      treatment with anti-CD154 or CTLA-4Ig to halt established allo-B cell responses.

PMID- 23855590
TI  - CAPN 7 promotes the migration and invasion of human endometrial stromal cell by
      regulating matrix metalloproteinase 2 activity.
AB  - BACKGROUND: Matrix metalloproteinase 2 (MMP-2) has been reported to be an
      important regulator of cell migration and invasion through degradation of the
      extracellular matrix (ECM) in many diseases, such as cancer and endometriosis.
      Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was
      markedly upregulated in the eutopic endometrium and endometrial stromal cells of
      women diagnosed with endometriosis. Our studies were carried out to detect the
      effects of CAPN 7 on human endometrial stromal cell (hESC) migration and
      invasion. METHODS: Western blotting and quantitative real-time PCR were used to
      detect the expression of CAPN 7 in endometriosis patients and normal fertile
      women. Scratch-wound-healing and invasion chamber assay were used to investigate
      the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative
      real-time PCR and zymography were carried out to detect the effect of CAPN 7 on
      the expressions and activity of MMP-2. RESULTS: CAPN 7 was markedly up-regulated
      in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7
      overexpression led to increased expression of MMP-2 and tissue inhibitor of
      metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7
      increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also
      found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7
      overexpression on hESC migration and invasion by approximately 50% and 55%,
      respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN
      7 interacted with activator protein 2alpha (AP-2alpha): an important
      transcription factor of MMP-2. CONCLUSIONS: CAPN 7 promotes hESC migration and
      invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to
      TIMP-2.

PMID- 23855592
TI  - Estimating energy losses with urine in the cat.
AB  - Urinary energy losses in cats have to be determined in energy balance trials as
      well as for the calculation of the metabolizable energy (ME) content of cat food.
      The aim of the present study was: first, to assess whether the energy content of
      cat urine quantified by bomb calorimetry differs from that quantified using GE
      (kJ) urine = 33 kJ * g C urine + 9 kJ * g N urine and investigate whether this
      difference could be attributed to influences of diets. Second, to assess whether
      the subtraction of 3.1 kJ/g of protein intake used for estimation of
      metabolizable energy content of cat foods is confirmed as usable. Data from 27
      energy and protein balance trials from different studies with complete sampling
      of urine and faeces (29 cats in part A and 35 cats in part B) were used. Gross
      energy, carbon and nitrogen were determined in food, faeces and urine. Gross
      energy values in urine tended to be higher when determined with the formula of
      Hoffman and Klein compared to bomb calorimetry. The average relative difference
      of gross energy values between the methods was 18.8%. The mean energy loss in
      kJ/g of protein intake resulted in 3.7 kJ/g protein intake, which was not
      statistically significantly different (p = 0.12) from the tested value of 3.1
      kJ/g of protein intake. In conclusion, the formula of Hoffman and Klein is not
      appropriate for the estimation of energy in cat urine. In balance studies, it is
      advisable to quantify the urinary energy content by bomb calorimetry. In the
      second part of the study, the protein correction factor to determine ME of 3.1
      kJ/g protein intake for urinary energy losses of Kienzle et al. could be
      confirmed. 

PMID- 23855591
TI  - Cervical dystonia: effectiveness of a standardized physical therapy program;
      study design and protocol of a single blind randomized controlled trial.
AB  - BACKGROUND: Cervical dystonia is characterized by involuntary muscle contractions
      of the neck and abnormal head positions that affect daily life activities and
      social life of patients. Patients are usually treated with botulinum toxin
      injections into affected neck muscles to relief pain and improve control of head
      postures. In addition, many patients are referred for physical therapy to improve
      their ability to perform activities of daily living. A recent review on allied
      health interventions in cervical dystonia showed a lack of randomized controlled
      intervention studies regarding the effectiveness of physical therapy
      interventions. METHODS/DESIGN: The (cost-) effectiveness of a standardized
      physical therapy program compared to regular physical therapy, both as add-on
      treatment to botulinum toxin injections will be determined in a multi-centre,
      single blinded randomized controlled trial with 100 cervical dystonia patients.
      Primary outcomes are disability in daily functioning assessed with the disability
      subscale of the Toronto Western Spasmodic Torticollis Rating Scale. Secondary
      outcomes are pain, severity of dystonia, active range of motion of the head,
      quality of life, anxiety and depression. Data will be collected at baseline,
      after six months and one year by an independent blind assessor just prior to
      botulinum toxin injections. For the cost effectiveness, an additional economic
      evaluation will be performed with the costs per quality adjusted life-year as
      primary outcome parameter. DISCUSSION: Our study will provide new evidence
      regarding the (cost-) effectiveness of a standardized, tailored physical therapy
      program for patients with cervical dystonia. It is widely felt that allied health
      interventions, including physical therapy, may offer a valuable supplement to the
      current therapeutic options. A positive outcome will lead to a greater use of the
      standardized physical therapy program. For the Dutch situation a positive outcome
      implies that the standardized physical therapy program forms the basis for a
      national treatment guideline for cervical dystonia. TRIAL REGISTRATION: Number
      Dutch Trial registration (Nederlands Trial Register): NTR3437.

PMID- 23855593
TI  - An update on drug-drug interactions with biologics for the treatment of moderate
      to-severe psoriasis.
AB  - OBJECTIVE: Moderate-to-severe psoriasis is a chronic skin condition that often
      requires systemic therapy and biologics are the newest systemic treatment
      available. A favorable aspect of biologics is that they are thought to have
      minimal risks for drug-drug interactions compared to oral systemic medications
      such as cyclosporine and methotrexate. However, this assumption has not been
      recently or adequately reviewed. We reviewed the literature to identify possible
      drug-drug interactions with biologics and other medications. METHODS: We searched
      PubMed for published case reports, clinical studies, reviews, and Food and Drug
      Administration (FDA) labels discussing possible drug-drug interactions with
      biologics for the treatment of moderate-to-severe psoriasis. RESULTS: There were
      only a small number of published articles describing drug-drug interactions with
      biologics. Our review identified two case reports, five clinical studies, and
      three pharmacokinetics reviews. The majority of articles did not observe
      clinically relevant drug-drug interactions with biologics. FDA labels do suggest
      a possible relationship between tumor necrosis factor (TNF)-alpha inhibitors and
      cytochrome P450 (CYP) activity. CONCLUSION: The paucity of information regarding
      drug-drug interactions reaffirms the idea that biologics have limited
      susceptibility to drug-drug interactions compared to other oral medications.
      Further studies are needed to adequately assess drug-drug interactions with
      biologics.

PMID- 23855594
TI  - Quality of life of adult clients on renal replacement therapies in Nepal.
AB  - AIM: To compare the influence of demographic and clinical variables on quality of
      life (QOL) amongst haemodialysis (HD) and renal transplantation clients in Nepal.
      BACKGROUND: Renal replacement therapy in the form of renal transplant is a newer
      modality in Nepal. In this study, effectiveness of renal transplant and
      maintenance HD in clients with end-stage renal disease were evaluated in a
      Nepalese context. METHOD: A descriptive, cross-sectional study was conducted to
      compare the QOL of clients undergoing HD and renal transplantation in two
      treatment centres in Nepal. Information on QOL was collected by using the WHOQOL
      BREF instrument through interviews. RESULT: The clients in the transplantation
      groups were significantly younger, highly educated and employed. The QOL score of
      clients with renal transplantation was significantly higher in the physical,
      psychological and social relationship domains. While assessing QOL score in
      transplantation groups, females scored significantly higher score in the
      environmental domain compared with males. CONCLUSION: The QOL score in renal
      transplant recipients was significantly better than that of clients on HD in
      three of the four WHOQOL-BREF domains. The limited resources and facilities for
      renal transplantation and the post-transplant follow-up service in Nepal might
      have contributed to a poorer outcome on the environmental domain in this group.

PMID- 23855595
TI  - Management of acute respiratory distress syndrome in a French Bulldog using
      airway pressure release ventilation.
AB  - OBJECTIVE: To describe the successful clinical management of a dog with acute
      respiratory distress syndrome (ARDS) using airway pressure release ventilation
      (APRV). CASE SUMMARY: An 18-month-old female French Bulldog was presented for
      routine ovariohysterectomy and correction of brachycephalic airway obstruction
      syndrome. Following the surgical procedures, the dog developed aspiration
      pneumonia and ARDS. Her clinical condition failed to improve with conventional
      pressure-support mechanical ventilation and she was subsequently managed with
      APRV. She recovered fully and exhibited no clinical or radiographic abnormalities
      during follow-up examinations. NEW OR UNIQUE INFORMATION PROVIDED: This is the
      first reported use of APRV to manage refractory hypoxemia associated with ARDS in
      a dog. This alternative mode of mechanical ventilation can be considered a
      feasible alternative in canine patients with ARDS.

PMID- 23855597
TI  - A functional natural dentition for all--and for life? The oral healthcare system
      needs revision.
AB  - The cost of dental care adds to the costs of the already overburdened health
      sector. Do we - as patients and as society -receive oral health care that is both
      aligned with the actual disease experience and also, critically based on up-to
      date scientific knowledge about the major oral diseases? In many places, the
      practice of dentistry reflects a response to disease patterns that once existed
      and is based on diagnostic and therapeutic approaches that are no longer valid.
      Instead, a new cadre of dental professionals is needed, one that is capable of
      meeting the actual health needs of our populations. This cadre should ensure that
      patients maintain a functioning dentition from cradle to grave based on cost
      effective disease control principles. There is an urgent need to: (i) reconsider
      the roles of the different oral health cadres involved in the provision of oral
      health care; (ii) integrate oral health into general healthcare services; and
      (iii) restructure the training of oral health personnel. We advocate a radical
      reform of the oral healthcare system involving the training of two new types of
      professionals integrated with the general healthcare system: The oral healthcare
      provider - a highly skilled professional specialised in the diagnosis and control
      of oral diseases and with a profound understanding of oral health as part of
      general health - and the oral clinical specialist - whose role is the provision
      of advanced oral rehabilitation, able also to treat people with complex chronic
      diseases and multiple medications. 

PMID- 23855596
TI  - Strength Training for Arthritis Trial (START): design and rationale.
AB  - BACKGROUND: Muscle loss and fat gain contribute to the disability, pain, and
      morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is
      an independent and modifiable risk factor for it. However, while all published
      treatment guidelines recommend muscle strengthening exercise to combat loss of
      muscle mass and strength in knee OA patients, previous strength training studies
      either used intensities or loads below recommended levels for healthy adults or
      were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity
      strength training in improving OA symptoms, slowing progression, and affecting
      the underlying mechanisms has not been examined due to the unsubstantiated belief
      that it might exacerbate symptoms. We hypothesize that in addition to short-term
      clinical benefits, combining greater duration with high-intensity strength
      training will alter thigh composition sufficiently to attain long-term reductions
      in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and
      slow OA progression. METHODS/DESIGN: This is an assessor-blind, randomized
      controlled trial. The study population consists of 372 older (age >= 55 yrs)
      ambulatory, community-dwelling persons with: (1) mild-to-moderate medial
      tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus
      aligned knee ( -2 degrees  valgus <= angle <= 10 degrees  varus); (3) 20 kg.m-2
      >= BMI <= 45 kg.m-2; and (3) no participation in a formal strength-training
      program for more than 30 minutes per week within the past 6 months. Participants
      are randomized to one of 3 groups: high-intensity strength training (75-90%
      1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or
      healthy living education. The primary clinical aim is to compare the
      interventions' effects on knee pain, and the primary mechanistic aim is to
      compare their effects on knee-joint compressive forces during walking, a
      mechanism that affects the OA disease pathway. Secondary aims will compare the
      interventions' effects on additional clinical measures of disease severity (e.g.,
      function, mobility); disease progression measured by x-ray; thigh muscle and fat
      volume, measured by computed tomography (CT); components of thigh muscle
      function, including hip abductor strength and quadriceps strength, and power;
      additional measures of knee-joint loading; inflammatory and OA biomarkers; and
      health-related quality of life. DISCUSSION: Test-retest reliability for the thigh
      CT scan was: total thigh volume, intra-class correlation coefficients (ICC) =
      0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for
      both isokinetic concentric knee flexion and extension strength was 0.93, and for
      hip-abductor concentric strength was 0.99. The reliability of our 1RM testing
      was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98.
      Results of this trial will provide critically needed guidance for clinicians in a
      variety of health professions who prescribe and oversee treatment and prevention
      of OA-related complications. Given the prevalence and impact of OA and the
      widespread availability of this intervention, assessing the efficacy of optimal
      strength training has the potential for immediate and vital clinical impact.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT01489462.

PMID- 23855598
TI  - Generalizing observational study results: applying propensity score methods to
      complex surveys.
AB  - OBJECTIVE: To provide a tutorial for using propensity score methods with complex
      survey data. DATA SOURCES: Simulated data and the 2008 Medical Expenditure Panel
      Survey. STUDY DESIGN: Using simulation, we compared the following methods for
      estimating the treatment effect: a naive estimate (ignoring both survey weights
      and propensity scores), survey weighting, propensity score methods (nearest
      neighbor matching, weighting, and subclassification), and propensity score
      methods in combination with survey weighting. Methods are compared in terms of
      bias and 95 percent confidence interval coverage. In Example 2, we used these
      methods to estimate the effect on health care spending of having a generalist
      versus a specialist as a usual source of care. PRINCIPAL FINDINGS: In general,
      combining a propensity score method and survey weighting is necessary to achieve
      unbiased treatment effect estimates that are generalizable to the original survey
      target population. CONCLUSIONS: Propensity score methods are an essential tool
      for addressing confounding in observational studies. Ignoring survey weights may
      lead to results that are not generalizable to the survey target population. This
      paper clarifies the appropriate inferences for different propensity score methods
      and suggests guidelines for selecting an appropriate propensity score method
      based on a researcher's goal.

PMID- 23855600
TI  - Anodic oxidation of disulfides: detection and reactions of disulfide radical
      cations.
AB  - The anodic oxidation of five diaryldisulfides have been studied in a
      dichloromethane/[NBu4][B(C6F5)4] electrolyte. Cyclic voltammetry scans of (p
      RC6H4)2S2 (R = Me, 1a; R = F, 1b; R = OMe, 1c) show modest chemical reversibility
      for the 1(0/+) couple (E1/2 values vs ferrocene: 1.04 V for 1a, 1.21 V for 1b,
      0.92 V for 1c), providing the first voltammetric evidence for the radical cation
      [Ar2S2](+). A dimer dication, [Ar4S4](2+), is proposed as an intermediate in the
      formation of the electrolysis product, the trisulfide [Ar3S3](+). The chemical
      reversibility of the one-electron oxidations of Ar2S2 vanishes in [PF6](-)
      containing electrolytes. The radical cations of the more sterically constrained
      ortho-substituted analogues dimesityldisulfide (2a, E1/2 = 1.01 V) and bis(2,4,6
      triisopropylphenyl)disulfide (2b, E1/2 = 0.98 V) show less tendency to dimerize.
      In all cases except 2b, the bulk electrolysis product is [R3S3](+), consistent
      with earlier literature reports. A mechanism is proposed in which the trisulfide
      is formed by reaction of the dimer dication [Ar4S4](2+) with neutral Ar2S2 to
      afford the trisulfide in a net 2/3 e(-) process. Oxidation of Ar2S2, either
      anodically or by a strong one-electron oxidant, in the presence of cyclohexene
      gives an efficient synthetic route to 1,2-substituted cyclohexyldisulfides. 

PMID- 23855601
TI  - Effect of extracorporeal magnetic energy stimulation on bothersome lower urinary
      tract symptoms and quality of life in female patients with stress urinary
      incontinence and overactive bladder.
AB  - AIMS: The aim of this study was to investigate the efficacy of extracorporeal
      magnetic stimulation (EMS) for the treatment of bothersome and severe symptoms of
      stress urinary incontinence (SUI) and overactive bladder syndrome (OAB) in female
      patients. MATERIAL AND METHODS: A retrospective review was conducted on patients
      with SUI and OAB who were referred to EMS therapy. Successful treatment for the
      bothersome symptoms of OAB and SUI was defined as score <=1 for questions 2 and 3
      on the Urodynamic Distress Inventory-6. The objective cure of SUI and OAB was
      defined as no urinary leakage during the cough stress test and any urgency, urge
      incontinence and voiding frequency of less than eight times per 24 h based on the
      3-day bladder diary, after the 9 weeks of treatment, respectively. RESULTS:
      Ninety-three patients with SUI or OAB underwent a 9-week course of EMS at 20 min
      twice weekly. Seventy-two (77%) patients completed EMS treatment. Geographical
      factor and poor economic status were two main factors for dropout. A total of
      94.1% (32 of 34) and 86.8% (33 of 38) of subjects had successful treatment for
      the bothersome symptoms of OAB and SUI, respectively. In contrast, the cure rate
      for OAB and SUI was only 61.7% and 42.1%, respectively. There was also a
      significant improvement in both Urogenital Distress Inventory Short Form
      (bothersome on lower urinary tract symptoms) and the Incontinence Impact
      Questionnaire Short Form (quality of life) total score in both groups after EMS.
      CONCLUSIONS: EMS is a safe and effective alternative method for treating SUI and
      OAB. Further studies are needed to evaluate the long-term efficacy.

PMID- 23855599
TI  - Model for high-throughput screening of multitarget drugs in chemical
      neurosciences: synthesis, assay, and theoretic study of rasagiline carbamates.
AB  - The disappointing results obtained in recent clinical trials renew the interest
      in experimental/computational techniques for the discovery of neuroprotective
      drugs. In this context, multitarget or multiplexing QSAR models (mt-QSAR/mx-QSAR)
      may help to predict neurotoxicity/neuroprotective effects of drugs in multiple
      assays, on drug targets, and in model organisms. In this work, we study a data
      set downloaded from CHEMBL; each data point (>8000) contains the values of one
      out of 37 possible measures of activity, 493 assays, 169 molecular or cellular
      targets, and 11 different organisms (including human) for a given compound. In
      this work, we introduce the first mx-QSAR model for neurotoxicity/neuroprotective
      effects of drugs based on the MARCH-INSIDE (MI) method. First, we used MI to
      calculate the stochastic spectral moments (structural descriptors) of all
      compounds. Next, we found a model that classified correctly 2955 out of 3548
      total cases in the training and validation series with Accuracy, Sensitivity, and
      Specificity values>80%. The model also showed excellent results in Computational
      Chemistry simulations of High-Throughput Screening (CCHTS) experiments, with
      accuracy=90.6% for 4671 positive cases. Next, we reported the synthesis,
      characterization, and experimental assays of new rasagiline derivatives. We
      carried out three different experimental tests: assay (1) in the absence of
      neurotoxic agents, assay (2) in the presence of glutamate, and assay (3) in the
      presence of H2O2. Compounds 11 with 27.4%, 8 with 11.6%, and 9 with 15.4% showed
      the highest neuroprotective effects in assays (1), (2), and (3), respectively.
      After that, we used the mx-QSAR model to carry out a CCHTS of the new compounds
      in >400 unique pharmacological tests not carried out experimentally.
      Consequently, this model may become a promising auxiliary tool for the discovery
      of new drugs for the treatment of neurodegenerative diseases.

PMID- 23855602
TI  - In vitro and in vivo evaluation of a new large animal spirometry device using
      mainstream CO2 flow sensors.
AB  - REASONS FOR PERFORMING STUDY: A spirometry device equipped with mainstream CO2
      flow sensor is not available for large animal anaesthesia. OBJECTIVES: To measure
      the resistance of a new large animal spirometry device and assess its agreement
      with reference methods for volume measurements. STUDY DESIGN: In vitro experiment
      and crossover study using anaesthetised horses. METHODS: A flow partitioning
      device (FPD) equipped with 4 human CO2 flow sensors was tested. Pressure
      differences were measured across the whole FPD and across each sensor separately
      using air flows (range: 90-720 l/min). One sensor was connected to a spirometry
      monitor for in vitro volume (3, 5 and 7 l) measurements. These measurements were
      compared with a reference method. Five anaesthetised horses were used for tidal
      volume (VT) measurements using the FPD and a horse-lite sensor (reference
      method). Bland-Altman analysis, ANOVA and linear regression analysis were used
      for data analysis. RESULTS: Pressure differences across each sensor were similar
      suggesting equal flow partitioning. The resistance of the device increased with
      flow (range: 0.3-1.5 cmH2 O s/l) and was higher than that of the horse-lite. The
      limits of agreement for volume measurements were within -1 and 2% in vitro and 
      12 and 0% in vivo. Nine of 147 VT measurements in horses were outside of the +/-
      10% limits of acceptance but most of these erroneous measurements occurred with
      VTs lower than 4 l. The determined correction factor for volume measurements was
      3.97 +/- 0.03. CONCLUSIONS: The limits of agreement for volume measurements by
      the new device were within +/- 10% using clinically relevant range of volumes.
      The new spirometry device can be recommended for measurement of VT in adult
      Warmblood horses.

PMID- 23855603
TI  - RNA polymerase: in search of promoters.
AB  - Transcription initiation is a key event in the regulation of gene expression. RNA
      polymerase (RNAP), the central enzyme of transcription, is able to efficiently
      locate promoters in the genome, carry out promoter opening, and initiate RNA
      synthesis. All the substeps of transcription initiation are subject to complex
      cellular regulation. Understanding the molecular details of each step in the
      promoter-opening pathway is essential for a complete mechanistic and quantitative
      picture of gene expression. In this minireview, primarily using bacterial RNAP as
      an example, I briefly summarize some of the key recent advances in our
      understanding of the mechanisms of promoter search and promoter opening. 

PMID- 23855604
TI  - Ambulatory arterial stiffness index in children after kidney transplantation.
AB  - Given the increase in CV morbidity after RTx and the scarcity of CV events in
      pediatrics, surrogate markers should be assessed to characterize CV damage in
      this population. AASI is a marker of arterial stiffness in adults, predicting
      cardio- and cerebrovascular morbidity. Our aim was to assess the determinants of
      AASI in RTx children (n = 54, 15.5 +/- 3.5 yr) and to examine its relationship to
      central PWV. AASI was calculated from 24 h ABPM. PWV was determined by
      applanation tonometry, body composition by multifrequency bioimpedance
      measurement. The dipping state, volume overload, and time on dialysis were the
      main predictors of AASI (p < 0.05). Children with established HT (n = 34) had
      increased AASI, extracellular body water, and BNP (p < 0.05). In contrast to
      AASI, PWV did not differ between HT and normotensive RTx patient groups. There
      was no correlation between AASI and PWV. PWV was increased in children who spent
      more than one yr on dialysis prior to RTx. In conclusion, increased AASI in HT
      RTx children better characterizes the actual volume- and pressure-dependent
      arterial rigidity rather than long-term morphological changes in large arteries
      as reflected by PWV. 

PMID- 23855605
TI  - Chromogenic chemical probe for protein structural characterization via
      ultraviolet photodissociation mass spectrometry.
AB  - A chemical probe/ultraviolet photodissociation (UVPD) mass spectrometry strategy
      for evaluating structures of proteins and protein complexes is reported, as
      demonstrated for lysozyme and beta-lactoglobulin with and without bound ligands.
      The chemical probe, NN, incorporates a UV chromophore that endows peptides with
      high cross sections at 351 nm, a wavelength not absorbed by unmodified peptides.
      Thus, NN-modified peptides can readily be differentiated from nonmodified
      peptides in complex tryptic digests created upon proteolysis of proteins after
      their exposure to the NN chemical probe. The NN chemical probe also affords two
      diagnostic reporter ions detected upon UVPD of the NN-modified peptide that
      provides a facile method for the identification of NN peptides within complex
      mixtures. Quantitation of the modified and unmodified peptides allows estimation
      of the surface accessibilities of lysine residues based on their relative
      reactivities with the NN chemical probe. 

PMID- 23855606
TI  - Electrospun upconversion composite fibers as dual drugs delivery system with
      individual release properties.
AB  - Novel multifunctional poly(epsilon-caprolactone)-gelatin encapsulating
      upconversion core/shell silica nanoparticles (NPs) composite fibers as dual drugs
      delivery system (DDDS), with indomethacin (IMC) and doxorubicin (DOX) releasing
      in individual release properties, have been designed and fabricated via
      electrospinning process. Uniform and monodisperse upconversion (UC) luminescent
      NaYF4:Yb(3+), Er(3+) nanocrystals (UCNCs) were encapsulated with mesoporous
      silica shells, resulting in the formation of core/shell structured NaYF4:Yb(3+),
      Er(3+)@mSiO2 (UCNCs@mSiO2) NPs, which can be performed as DOX delivery carriers.
      These UCNCs@mSiO2 NPs loading DOX then were dispersed into the mixture of
      poly(epsilon-caprolactone) (PCL) and gelatin-based electrospinning solution
      containing IMC, followed by the preparation of dual drug-loaded composite fibers
      (DDDS) via electrospinning method. The drugs release profiles of the DDDS were
      measured, and the results indicated that the IMC and DOX released from the
      electrospun composite fibers showed distinct properties. The IMC in the composite
      fibers presented a fast release manner, while DOX showed a sustained release
      behavior. Moreover, the UC luminescent intensity ratios of (2)H(11/2)/(4)S(3/2)
      (4)I(15/2) to (4)F(9/2)-(4)I(15/2) from Er(3+) vary with the amounts of DOX in
      the system, and thus drug release can be tracked and monitored by the
      luminescence resonance energy transfer (LRET) mechanism.

PMID- 23855607
TI  - Emotional intelligence, self-efficacy, and occupational therapy students'
      fieldwork performance.
AB  - This study explored the relationship of emotional intelligence level and self
      efficacy to fieldwork performance for occupational therapy students. Occupational
      therapy students (n = 199) from 36 occupational therapy programs in the United
      States completed the two surveys, the Mayer-Salovey-Caruso Emotional Intelligence
      Test and the Student Confidence Questionnaire, during their professional Level 2
      fieldwork placements. The surveys were compared to the Fieldwork Performance
      Evaluation for the Occupational Therapy Student completed by the fieldwork
      educators. Results showed that degree of emotional intelligence, having a choice
      in the fieldwork setting, and having professional experience in a related setting
      were positively correlated to Fieldwork Performance scores. Students' self
      efficacy was not related to Fieldwork Performance scores. This suggests fostering
      students' emotional intelligence and capacity for accurate skill appraisal
      supports fieldwork success.

PMID- 23855608
TI  - Occupational therapy community practice and home assessments: use of the home
      safety self-assessment tool (HSSAT) to support aging in place.
AB  - More than 70 million Americans are expected to be 65 years or older by 2030, with
      8.7 million 85 or older. Occupational therapists can provide client and
      population-centered interventions to promote home safety, functional abilities,
      and quality of life to support older adults' desires for independence and to age
      in place. This includes the use of assistive technology, home modifications, and
      rehabilitation principles, to design real life solutions to support the needs of
      older adults. Using case study methodology this paper focuses on the development
      and pilot-testing of the Home Safety Self-Assessment Tool (HSSAT), a new home
      assessment, designed for use by older individuals to promote home safety and
      aging in place. The results suggest the tool may assist older adults in
      identifying environmental factors that are related to falls and facilitate their
      ability to age in place.

PMID- 23855609
TI  - The utilization of occupational therapy services for persons with Charcot-Marie
      Tooth disease.
AB  - The purpose of this study was to investigate the utilization of occupational
      therapy services in persons with Charcot-Marie-Tooth (CMT) disease, to better
      understand if services are being provided, the types of interventions being
      provided, and satisfaction of services. Using survey methods, an online
      questionnaire was made available to persons with CMT listed on association
      websites worldwide. One hundred and fifteen persons with CMT, residing in all
      geographical regions within the United States and seven other countries
      participated in the study. Around half of all participants had received
      occupational therapy services. Twelve interventions were identified as being
      provided for persons with CMT. Although the majority of individuals receiving
      occupational therapy services did not feel like it improved their quality of
      life, the majority of individuals would recommend occupational therapy services
      to others and would return to an occupational therapist. Of those participants
      not receiving occupational therapy, the majority felt they would benefit from
      occupational therapy services. The results suggest that occupational therapy
      services are not being well utilized for this population. A low response rate
      limits generalization, thus further research is necessary.

PMID- 23855610
TI  - Health status of people with work-related musculoskeletal disorders in return to
      work programs: a Malaysian study.
AB  - This study examined the health status of injured workers with musculoskeletal
      disorders enrolled in the Malaysian Return to Work (RTW) program. The 102
      participants were categorized into three RTW groups: Off-work (n = 30, 29.4%), Re
      entry (n = 44, 43.1%), and Maintenance (n = 28, 27.5%). Overall health status, as
      measured by the SF-36 version 2, of the workers exhibited below average compared
      to the internationally established normative population, with their physical
      health component summary rated lower than mental health. Across the different
      groups, significant differences were found in role-physical, vitality, bodily
      pain, general health, and mental health. However, the mean values of these
      variables were higher in the Maintenance group and were found significant. The
      current health status of injured workers at Off-work and Re-entry phases was
      significantly low and warranted to be improved by involving other health
      professionals such as occupational therapists, ergonomists, and psychologists.

PMID- 23855611
TI  - Occupational therapy practitioners' knowledge and perceptions of childhood asthma
      and cystic fibrosis.
AB  - This study surveyed pediatric occupational therapy practitioners regarding their
      knowledge and perceptions about the chronic respiratory diseases (CRDs) asthma
      and cystic fibrosis which affect the functioning and quality of life for millions
      of children. Surveys were mailed to 250 members of the Ohio Occupational Therapy
      Association's pediatric member support group. Though 104 occupational therapy
      practitioners returned completed surveys, only the 82 who were currently
      practicing in pediatric settings were included in analysis. Respondents scored an
      average of 77% (SD = 10%) on a test of knowledge about asthma and cystic
      fibrosis. Respondents demonstrated several misperceptions about of the effects of
      these diseases on everyday life. A large majority (91%) endorsed one or more
      roles for occupational therapy with children with chronic respiratory diseases.
      Respondents indicated that confusion about the role of occupational therapy is a
      barrier to practice with children with CRDs. The results may prompt educational
      curricula to make adjustments, while continuing education courses may expand in
      addressing CRDs.

PMID- 23855613
TI  - Distance education and teaching online: my journey from mystery to mastery.
AB  - With the burgeoning of online programs in higher education, many occupational
      therapy faculty will need to expand their teaching repertoire to include distance
      education methods. This article describes the transition of one teacher, moving
      from face to face instruction to a blended distance education format, and the
      components of the process. These include providing a good technical
      infrastructure and training for both teachers and students. In addition, the
      process of creating and developing both synchronous (live) sessions and
      asynchronous (discussion boards) are described. Lastly the author reflects on
      ways to transcend the distance and strengthen the online learning experience.

PMID- 23855618
TI  - Mechanisms and rescue strategies of calcineurin inhibitor mediated tolerance
      abrogation induced by anti-CD4 mAb treatment.
AB  - To ensure safety tolerance induction protocols are accompanied by conventional
      immunosuppressive drugs (IS). But IS such as calcineurin inhibitors (CNI), for
      example, cyclosporin A (CsA), can interfere with tolerance induction. We
      investigated the effect of an additional transient CsA treatment on anti-CD4mAb
      induced tolerance induction upon rat kidney transplantation. Additional CsA
      treatment induced deteriorated graft function, resulting in chronic rejection
      characterized by glomerulosclerosis, interstitial fibrosis, tubular atrophy and
      vascular changes. Microarray analysis revealed enhanced intragraft expression of
      the B cell attracting chemokine CXCL13 early during CsA treatment. Increase in
      CXCL13 expression is accompanied by enhanced B cell infiltration with local and
      systemic IgG production and C3d deposition as early as 5 days upon CsA
      withdrawal. Adding different CNIs to cultures of primary mesangial cells isolated
      from glomeruli resulted in a concentration-dependent increase in CXCL13
      transcription. CsA in synergy with TNF-alpha can enhance the B cell attracting
      and activating potential of mesangial cells. Transient B cell depletion or
      transfer of splenocytes from tolerant recipients 3 weeks after transplantation
      could rescue tolerance induction and did inhibit intragraft B cell accumulation,
      alloantibody production and ameliorate chronic rejection.

PMID- 23855619
TI  - Comment on 'Predicting treatment response in psoriasis using serum levels of
      adalimumab and etanercept: a single-centre, cohort study': reply from authors.

PMID- 23855620
TI  - Risk factors for drug-resistant pathogens in community-acquired and healthcare
      associated pneumonia.
AB  - RATIONALE: Identification of patients with drug-resistant pathogens at initial
      diagnosis is essential for treatment of pneumonia. OBJECTIVES: To elucidate
      clinical features of community-acquired pneumonia (CAP) and healthcare-associated
      pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in
      patients with CAP and HCAP. METHODS: A prospective observational study was
      conducted in hospitalized patients with pneumonia at 10 institutions in Japan.
      Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam,
      macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant
      pathogens (CAP-DRPs). MEASUREMENTS AND MAIN RESULTS: In total, 1,413 patients
      (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in
      patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk
      factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These
      included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence
      interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11),
      previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid
      suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95%
      CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the
      combined patients with CAP and HCAP. The area under the receiver operating
      characteristic curve for counting the number of risk factors was 0.79 (95% CI,
      0.74-0.84). CONCLUSIONS: The clinical profile of HCAP was different from that of
      CAP. However, physicians can predict drug resistance in patients with either CAP
      or HCAP by taking account of the cumulative number of the risk factors. Clinical
      trial registered with https://upload.umin.ac.jp/cgi-open
      bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004001&langu
      ge=E ; number UMIN000003306.

PMID- 23855621
TI  - Acaricidal potentials of active properties isolated from Cynanchum paniculatum
      and acaricidal changes by introducing functional radicals.
AB  - This study evaluated the acaricidal activities of acetophenone and its
      derivatives for their potentials as natural acaricides using an impregnated
      fumigant bioassay against Dermatophagoides spp. and Tyrophagus putrescentiae . On
      the basis of the LD50 values against D. farinae, 3'-methoxyacetophenone (0.41
      MUg/cm(2)) was 89.9 times more toxic than DEET (36.87 MUg/cm(2)), followed by 4'
      methoxyacetophenone (0.52 MUg/cm(2)), 2'-methoxyacetophenone (0.75 MUg/cm(2)), 2'
      hydroxy-5'-methoxyacetophenone (1.03 MUg/cm(2)), 2'-hydroxy-4'
      methoxyacetophenone (1.29 MUg/cm(2)), acetophenone (1.48 MUg/cm(2)), 2'
      hydroxyacetophenone (1.74 MUg/cm(2)), 2',5'-dimethoxyacetophenone (1.87
      MUg/cm(2)), 2',4'-dimethoxyacetophenone (2.10 MUg/cm(2)), and benzyl benzoate
      (9.92 MUg/cm(2)). In regard to structure-activity relationships between
      acaricidal activity and functional radicals (hydroxyl and methoxy groups) on the
      acetophenone skeleton, a monomethoxy group (2'-, 3'-, and 4'-methoxyacetone) on
      the acetophenone skeleton was more toxic than were the other groups (2',4'- and
      2',5'-dimethoxyacetophenone, 2'- and 4'-hydroxyacetophenone, 2'-hydroxy-4'
      methoxyacetophenone, 2'-hydroxy-5'-methoxyacetophenone, and 4'-hydroxy-3'
      methoxyacetophenone). These results indicated that acaricidal activity against
      three mite species changed with the introduction of functional radicals (hydroxyl
      and methoxy groups) onto the acetophenone skeleton. 

PMID- 23855622
TI  - Prevalence, characteristics and correlates of a positive-dementia screen in
      patients on antiretroviral therapy in Bamenda, Cameroon: a cross-sectional study.
AB  - BACKGROUND: In this study we assess the prevalence, characteristics as well as
      socio-demographic and clinical correlates of a positive screen for HIV-associated
      dementia in a group of patients on antiretroviral therapy (ART) in Bamenda,
      Cameroon. METHODS: In a cross-sectional study, a structured questionnaire was
      used to collect data on 400 patients attending the Bamenda Regional Hospital AIDS
      treatment Centre. Patients were assessed for neurocognitive function using the
      International HIV Dementia Scale (IHDS) to assess finger-tapping (FT),
      alternating hand sequence (AHS) and a 4-word recall (4WR), each scored on a
      maximum of four. RESULTS: A total of 297 (74%) participants were females. The
      total IHDS score ranged from 6-12 with a mean of 9.02 and 85% of subjects
      screened positive for dementia (<=10 on IHDS). Participants performed worst in
      the AHS assessment with a mean of 2.25 (IQR: 2-3). In multivariable analyses,
      screening positive for dementia was significantly associated with having primary
      education or less (aOR: 8.33, 95%CI: 3.85, 16.67), and having HIV symptoms (aOR:
      12.16, 95%CI: 3.08, 48.05). CONCLUSIONS: A very high proportion of patients on
      ART screened positive for dementia using the IHDS. This could potentially be an
      indication of a high prevalence of HIV-associated neurocognitive disorders in
      this population and or a poor performance of the IHDS in patients on ART. Future
      studies will need to assess the validity of the IHDS in this population of
      patients on ART and also evaluate long term outcomes in patients with positive
      dementia screens.

PMID- 23855623
TI  - The characteristics of oviposition and hormonal and gene regulation of ovarian
      follicle development in Magang geese.
AB  - BACKGROUND: Egg laying in Magang geese is characterized by extended interruption
      between clutches and lowing laying rate. Both the ovarian follicular development
      and ovulation characteristics, and the associated endocrine and molecular
      regulatory mechanisms involved are poorly understood, but could be important for
      guiding development of molecule aided selection of egg laying performances in
      geese. This study, therefore, recorded egg-laying characteristics of Magang
      geese, and the endocrine and molecular regulatory mechanisms of ovarian
      follicular development, maturation, and ovulation in Magang geese. METHODS:
      Oviposition, ovarian follicle development, and reproductive hormone and gene
      expression profiles were observed in a small flock of Magang geese. RESULTS:
      Greater than 73% of eggs were laid during the day. The average oviposition
      interval was 46.8 h (36-55 h). It took approximately 18 days for large white
      follicles to develop into mature F1 follicles; follicular growth was exponential.
      LHR expression levels increased from the small to the large mature follicles, but
      FSHR expression decreased in the granulosa and thecal layers. As the follicles
      matured, inhibin alpha and inhibin betaA expression increased in the granulosa
      layer. Activin IR, activin IIRA, activin IIRB, and beta-glycan expressions also
      increased as the follicles increased in size, but were more abundantly expressed
      in the thecal than in the granulosa layers. During the oviposition cycle, plasma
      concentrations of gonadal hormones decreased rapidly, whereas the level of PGFM
      peaked around ovulation. The profiles of activin, inhibin, follistatin,
      estradiol, and progesterone leading to ovulation were characterized. CONCLUSIONS:
      The molecular and endocrine mechanisms that regulate follicular development in
      Magang geese are similar to those in chickens. Moreover, gonadotropin regulation
      and interaction between activin, inhibin, and follistatin secretion may govern 3
      stage maturation in the final preovulatory follicles in Magang geese. The rapid
      rebound of post-ovulatory secretions of inhibin and follistatin may inhibit
      recruitment of new SYF recruitment once a sequence of eggs is started, and may
      limit the egg clutch size to no more than the number of LYFs present before the
      first sequence egg.

PMID- 23855624
TI  - Case of chromoblastomycosis with pulmonary involvement.
AB  - Chromoblastomycosis is a slowly growing chronic cutaneous mycosis associated with
      a variety of cutaneous lesions. Extra-dermal involvement is rare. A 58-year-old
      man was admitted to the hospital with nausea, vomiting, weakness and a history of
      weight loss. On inspection, he had a large verrucous mass in the sacral region,
      and two large subcutaneous nodules in the anterior thoracic wall. He claimed the
      lesions were several years old. Biopsy and histological studies were positive for
      chromoblastomycosis. Routine chest radiography showed hilar enlargement, and a
      chest computed tomography was ordered. Pulmonary nodules were evident, and
      endoscopically acquired samples were also positive for chromoblastomycosis. Extra
      dermal and systemic involvement in chromoblastomycosis is exceedingly rare and
      often associated with immunosuppression. There is only one other case of
      pulmonary chromoblastomycosis reported in the published work. 

PMID- 23855626
TI  - Livestock development in China: animal production, consumption and genetic
      resources.

PMID- 23855625
TI  - Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic
      vascular smooth muscle cells.
AB  - BACKGROUND: The expression of myocardin, a cardiac-restricted gene, increases
      during environmental stress. How mechanical stretch affects the regulation of
      myocardin in vascular smooth muscle cells (VSMCs) is not fully understood. We
      identify the mechanisms and pathways through which mechanical stretch induces
      myocardin expression in VSMCs. RESULTS: Rat VSMCs grown on a flexible membrane
      base were stretched to 20% of maximum elongation, at 60 cycles per min. An in
      vivo model of aorta-caval shunt in adult rats was also used to investigate
      myocardin expression. Cyclic stretch significantly increased myocardin and
      angiotensin II (AngII) expression after 18 and 6 h of stretch. Addition of
      extracellular signal-regulated kinases (ERK) pathway inhibitor (PD98059), ERK
      small interfering RNA (siRNA), and AngII receptor blocker (ARB; losartan) before
      stretch inhibited the expression of myocardin protein. Gel shift assay showed
      that myocardin-DNA binding activity increased after stretch. PD98059, ERK siRNA
      and ARB abolished the binding activity induced by stretch. Stretch increased
      while myocardin-mutant plasmid, PD98059, and ARB abolished the promoter activity.
      Protein synthesis by measuring [3H]proline incorporation into the cells increased
      after cyclic stretch, which represented hypertrophic change of VSMCs. An in vivo
      model of aorta-caval shunt also demonstrated increased myocardin protein
      expression in the aorta. Confocal microscopy showed increased VSMC size 24 h
      after cyclic stretch and VSMC hypertrophy after creation of aorta-caval shunt for
      3 days. CONCLUSIONS: Cyclic stretch enhanced myocardin expression mediated by
      AngII through the ERK pathway in cultured rat VSMCs. These findings suggest that
      myocardin plays a role in stretch-induced VSMC hypertrophy.

PMID- 23855627
TI  - Unknown-parent groups in single-step genomic evaluation.
AB  - In single-step genomic evaluation using best linear unbiased prediction
      (ssGBLUP), genomic predictions are calculated with a relationship matrix that
      combines pedigree and genomic information. For missing pedigrees, unknown
      selection processes, or inclusion of several populations, a BLUP model can
      include unknown-parent groups (UPG) in the animal effect. For ssGBLUP, UPG
      equations also involve contributions from genomic relationships. When those
      contributions are ignored, UPG solutions and genetic predictions can be biased.
      Options to eliminate or reduce such bias are presented. First, mixed model
      equations can be modified to include contributions to UPG elements from genomic
      relationships (greater software complexity). Second, UPG can be implemented as
      separate effects (higher cost of computing and data processing). Third,
      contributions can be ignored when they are relatively small, but they may be
      small only after refinements to UPG definitions. Fourth, contributions may
      approximately cancel out when genomic and pedigree relationships are constructed
      for compatibility; however, different construction steps are required for unknown
      parents from the same or different populations. Finally, an additional polygenic
      effect that also includes UPG can be added to the model. 

PMID- 23855628
TI  - Genomic evaluations using similarity between haplotypes.
AB  - Long-range phasing and haplotype library imputation methodologies are accurate
      and efficient methods to provide haplotype information that could be used in
      prediction of breeding value or phenotype. Modelling long haplotypes as
      independent effects in genomic prediction would be inefficient due to the many
      effects that need to be estimated and phasing errors, even if relatively low in
      frequency, exacerbate this problem. One approach to overcome this is to use
      similarity between haplotypes to model covariance of genomic effects by region or
      of animal breeding values. We developed a simple method to do this and tested
      impact on genomic prediction by simulation. Results show that the diagonal and
      off-diagonal elements of a genomic relationship matrix constructed using the
      haplotype similarity method had higher correlations with the true relationship
      between pairs of individuals than genomic relationship matrices built using
      unphased genotypes or assumed unrelated haplotypes. However, the prediction
      accuracy of such haplotype-based prediction methods was not higher than those
      based on unphased genotype information. 

PMID- 23855629
TI  - A penalized likelihood approach to pooling estimates of covariance components
      from analyses by parts.
AB  - Estimates of covariance matrices for numerous traits are commonly obtained by
      pooling results from a series of analyses of subsets of traits. A penalized
      maximum-likelihood approach is proposed to combine estimates from part analyses
      while constraining the resulting overall matrices to be positive definite. In
      addition, this provides the scope for 'improving' estimates of individual
      matrices by applying a penalty to the likelihood aimed at borrowing strength from
      their phenotypic counterpart. A simulation study is presented showing that the
      new method performs well, yielding unpenalized estimates closer to results from
      multivariate analyses considering all traits, than various other techniques used.
      In particular, combining results for all sources of variation simultaneously
      minimizes deviations in phenotypic estimates if sampling covariances can be
      approximated. A mild penalty shrinking estimates of individual covariance
      matrices towards their sum or estimates of canonical eigenvalues towards their
      mean proved advantageous in most cases. The method proposed is flexible,
      computationally undemanding and provides combined estimates with good sampling
      properties and is thus recommended as alternative to current methods for pooling.

PMID- 23855630
TI  - Estimates of autozygosity derived from runs of homozygosity: empirical evidence
      from selected cattle populations.
AB  - Using genome-wide SNP data, we calculated genomic inbreeding coefficients (FROH 
      > 1  Mb , FROH  > 2 Mb , FROH  > 8 Mb and FROH  > 16 Mb ) derived from runs of
      homozygosity (ROH) of different lengths (>1, >2, >8 and > 16 Mb) as well as from
      levels of homozygosity (FHOM ). We compared these values of inbreeding
      coefficients with those calculated from pedigrees (FPED ) of 1422 bulls
      comprising Brown Swiss (304), Fleckvieh (502), Norwegian Red (499) and Tyrol Grey
      (117) cattle breeds. For all four breeds, population inbreeding levels estimated
      by the genomic inbreeding coefficients FROH  > 8 Mb and FROH  > 16 Mb were
      similar to the levels estimated from pedigrees. The lowest values were obtained
      for Fleckvieh (FPED  = 0.014, FROH  > 8 Mb  = 0.019 and FROH  > 16 Mb  = 0.008);
      the highest, for Brown Swiss (FPED  = 0.048, FROH  > 8 Mb  = 0.074 and FROH  > 16
      Mb  = 0.037). In contrast, inbreeding estimates based on the genomic coefficients
      FROH  > 1 Mb and FROH  > 2 Mb were considerably higher than pedigree-derived
      estimates. Standard deviations of genomic inbreeding coefficients were, on
      average, 1.3-1.7-fold higher than those obtained from pedigrees. Pearson
      correlations between genomic and pedigree inbreeding coefficients ranged from
      0.50 to 0.62 in Norwegian Red (lowest correlations) and from 0.64 to 0.72 in
      Tyrol Grey (highest correlations). We conclude that the proportion of the genome
      present in ROH provides a good indication of inbreeding levels and that analysis
      based on ROH length can indicate the relative amounts of autozygosity due to
      recent and remote ancestors. 

PMID- 23855631
TI  - Genome-wide linkage disequilibrium in the Blonde d'Aquitaine cattle breed.
AB  - We present here the first genome-wide characterization of linkage disequilibrium
      (LD) in the French Blonde d'Aquitaine (BLA) breed, a well-muscled breed renowned
      for producing high-yielding beef carcasses. To assess the pattern and extent of
      LD, we used a sample of 30 unrelated bulls and 36 923 single nucleotide
      polymorphisms (SNPs) covering all cattle autosomes. The squared correlation of
      the alleles at two loci (r(2) ) was used as a measure of LD. The analysis of
      adjacent marker pairs revealed that the level of LD decreases rapidly with
      physical distance between SNPs. Overall mean r(2) was 0.205 (+/-0.262). Strong LD
      (r(2)  > 0.8) and useful LD (measured as r(2 ) > 0.2) were observed within
      genomic regions of up to 720 and 724 kb, respectively. We analysed the genetic
      structure of the BLA population and found stratification. The observed genetic
      sub-structuring is consistent with the known recent demographic history that
      occurred during BLA breed formation. Our results indicate that LD mapping of
      phenotypic traits in the BLA population is feasible; however, because of this sub
      structuring, special care is needed to reduce the likelihood of false-positive
      associations between marker loci and traits of interest. 

PMID- 23855632
TI  - The contribution of dominance and inbreeding depression in estimating variance
      components for litter size in Pannon White rabbits.
AB  - In a synthetic closed population of Pannon White rabbits, additive (VA ),
      dominance (VD ) and permanent environmental (VPe ) variance components as well as
      doe (bF d ) and litter (bF l ) inbreeding depression were estimated for the
      number of kits born alive (NBA), number of kits born dead (NBD) and total number
      of kits born (TNB). The data set consisted of 18,398 kindling records of 3883
      does collected from 1992 to 2009. Six models were used to estimate dominance and
      inbreeding effects. The most complete model estimated VA and VD to contribute 5.5
      +/- 1.1% and 4.8 +/- 2.4%, respectively, to total phenotypic variance (VP ) for
      NBA; the corresponding values for NBD were 1.9 +/- 0.6% and 5.3 +/- 2.4%, for
      TNB, 6.2 +/- 1.0% and 8.1 +/- 3.2% respectively. These results indicate the
      presence of considerable VD . Including dominance in the model generally reduced
      VA and VPe estimates, and had only a very small effect on inbreeding depression
      estimates. Including inbreeding covariates did not affect estimates of any
      variance component. A 10% increase in doe inbreeding significantly increased NBD
      (bF d  = 0.18 +/- 0.07), while a 10% increase in litter inbreeding significantly
      reduced NBA (bF l  = -0.41 +/- 0.11) and TNB (bF l  = -0.34 +/- 0.10). These
      findings argue for including dominance effects in models of litter size traits in
      populations that exhibit significant dominance relationships. 

PMID- 23855633
TI  - Mitochondrial D-loop analysis reveals low diversity in Mangalica pigs and their
      relationship to historical specimens.
AB  - The genetic relationship between 195 Mangalica and 79 non-Mangalica pigs was
      studied using mitochondrial D-loop SNP genotyping. Altogether, 35 polymorphic
      sites and 27 haplotypes were identified. Of the haplotypes, eight and 16 are
      Mangalica and non-Mangalica specific, respectively, while three contain both
      Mangalica and non-Mangalica individuals. Genetic distance values and phylogenetic
      analysis indicate that Mangalica individuals are very closely related, and five
      haplotypes represent approximately 92% of the Mangalica pigs involved in the
      study, thus determining the major maternal lineages. In contrast to previous
      microsatellite studies, individuals of Mangalica could not be distinguished as
      three separate breeds using mtDNA genotyping. Comparing modern and archaeological
      mtDNA sequences revealed that present day Mangalica is related to pigs that lived
      in the Carpathian basin where postulated ancestors of Mangalica also lived. This
      is the first DNA-based genetic evidence to support the described breeding history
      of Mangalica. 

PMID- 23855634
TI  - Analysis of genetic diversity in Bolivian llama populations using
      microsatellites.
AB  - South American camelids (SACs) have a major role in the maintenance and potential
      future of rural Andean human populations. More than 60% of the 3.7 million llamas
      living worldwide are found in Bolivia. Due to the lack of studies focusing on
      genetic diversity in Bolivian llamas, this analysis investigates both the genetic
      diversity and structure of 12 regional groups of llamas that span the greater
      part of the range of distribution for this species in Bolivia. The analysis of 42
      microsatellite markers in the considered regional groups showed that, in general,
      there were high levels of polymorphism (a total of 506 detected alleles; average
      PIC across per marker: 0.66), which are comparable with those reported for other
      populations of domestic SACs. The estimated diversity parameters indicated that
      there was high intrapopulational genetic variation (average number of alleles and
      average expected heterozygosity per marker: 12.04 and 0.68, respectively) and
      weak genetic differentiation among populations (FST range: 0.003-0.052). In
      agreement with these estimates, Bolivian llamas showed a weak genetic structure
      and an intense gene flow between all the studied regional groups, which is due to
      the exchange of reproductive males between the different flocks. Interestingly,
      the groups for which the largest pairwise FST estimates were observed, Sud Lipez
      and Nor Lipez, showed a certain level of genetic differentiation that is probably
      due to the pattern of geographic isolation and limited communication
      infrastructures of these southern localities. Overall, the population parameters
      reported here may serve as a reference when establishing conservation policies
      that address Bolivian llama populations. 

PMID- 23855635
TI  - Nucleophilic ortho-allylation of pyrroles and pyrazoles: an accelerated
      Pummerer/thio-Claisen rearrangement sequence.
AB  - Arylsulfinyl groups direct the metal-free, regiospecific, nucleophilic ortho
      allylation of pyrroles and pyrazoles. Mechanistic studies support the
      intermediacy of allylsulfonium salts that undergo facile thio-Claisen
      rearrangement onto the heterocyclic ring, giving products of coupling. The
      strategy has been adapted to allow regiospecific propargylation of the
      heterocyclic substrates. 

PMID- 23855636
TI  - State-level unemployment and the utilization of preventive medical services.
AB  - OBJECTIVE: To study the association between macroeconomic conditions and
      preventive medical service utilization. DATA SOURCES/STUDY SETTING: Secondary
      data collection of a survey of the civilian, non-institutionalized population of
      adults (age 18 and older) in the United States between 1987 and 2010. STUDY
      DESIGN: Regression analyses that adjust for individual-level demographic and
      socioeconomic determinants, state and time-fixed effects, and state-specific time
      trends. DATA COLLECTION/EXTRACTION METHODS: State health departments, with
      technological and methodological assistance from the Centers for Disease Control
      and Prevention, conducted a cross-sectional yearly telephone survey using a
      standardized questionnaire. PRINCIPAL FINDINGS: The use of preventive medical
      services is procyclical: a 1 percentage point increase in the state-level
      unemployment rate is associated with a 1.58 percent decrease in the quantity of
      distinct preventive care services utilized. Women and economically disadvantaged
      populations are shown to be especially sensitive to macroeconomic fluctuations.
      CONCLUSIONS: Policy makers should be aware of cyclical changes in preventive care
      use, particularly among disadvantaged populations, when making challenging
      budgetary decisions during economic downturns. As physician recommendations can
      have a strong impact on patients' use, health care providers could increase
      efforts to persuade patients to seek screening exams and necessary vaccinations
      during periods of high unemployment.

PMID- 23855637
TI  - Hypoperfusion and acute traumatic coagulopathy in severely traumatized canine
      patients.
AB  - OBJECTIVE: To determine the incidence of acute traumatic coagulopathy in dogs
      suffering severe trauma and to investigate the association of markers of
      hypoperfusion with coagulation abnormalities. DESIGN: A prospective observational
      study performed June, 2009 to February, 2011. SETTING: A university teaching
      hospital. ANIMALS: Thirty client-owned dogs weighing >5 kilograms that were
      presented to the Tuft's Cummings School of Veterinary Medicine following severe
      trauma as defined by an animal trauma triage score (ATT) >=5 and having received
      no resuscitation with IV fluids or blood products prior to blood sampling.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Prior to resuscitation, data
      obtained at the time of admission to the emergency service included HCT, platelet
      count, lactate concentration, pH, base excess, thromboelastrogram (TEG),
      prothrombin time, activated partial thromboplastin time, fibrinogen level, and
      protein C activity. Rectal temperature and ATT were recorded for all dogs.
      Neither HCT nor platelet count was significantly decreased in any of the dogs.
      Based on G values as measured by TEG, 10/30 dogs (33%) showed evidence of
      hypercoagulability. Hypocoagulability as determined by prothrombin time,
      activated partial thromboplastin time, or TEG was not shown in any of the 30
      dogs. CONCLUSION: Dogs with severe trauma may experience hypercoagulability that
      is unrelated to fluid resuscitation or transfusion therapy. Future studies are
      warranted to better characterize coagulation changes in dogs with severe trauma,
      particularly in relationship to fluid therapies and/or hemorrhage.

PMID- 23855638
TI  - Obstetrical complications associated with first-trimester screening markers in
      twin pregnancies.
AB  - AIM: The aim of this retrospective study was to investigate the relation between
      perinatal complications in twin pregnancies and the combination of first
      trimester maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free
      beta-human chorionic gonadotrophin (beta-hCG) levels. MATERIAL AND METHODS: The
      study was conducted at the Perinatology Department of Baskent University between
      January 2005 and December 2011. In total, 104 patients with twin pregnancies were
      recruited. The association of first-trimester maternal serum-screening markers
      with perinatal complications was investigated for small-for-gestational-age (SGA)
      fetuses or intrauterine growth restriction (IUGR), preterm delivery (before 34
      weeks of gestation), pregnancy-induced hypertension (PIH), and growth discordance
      between fetuses. RESULTS: Low serum PAPP-A (below 10th percentile) levels were
      not correlated with preterm labor, PIH, or IUGR in twin gestations. Elevated free
      beta-hCG levels (>90th percentile) were linked to increased rates of PIH and
      small-for-gestational-age fetuses or IUGR. CONCLUSION: Elevated first-trimester
      free beta-hCG was related to adverse pregnancy outcomes in twin pregnancies,
      whereas low PAPP-A levels were not linked to adverse pregnancy outcomes.

PMID- 23855639
TI  - Tobacco use and caries risk among adolescents--a longitudinal study in Sweden.
AB  - BACKGROUND: Smoking and the use of smokeless tobacco have a detrimental impact on
      general and oral health. The relationship to dental caries is however still
      unclear. As caries is a multi-factorial disease with clear life-style, socio
      economic and socio-demographic gradients, the tobacco use may be a co-variable in
      this complex rather than a direct etiological factor. Our aim was to analyze the
      impact of tobacco use on caries incidence among adolescents, with consideration
      to socio-economic variables by residency, using epidemiological data from a
      longitudinal study in the region of Halland, Sweden. METHODS: The study
      population consisted of 10,068 adolescents between 16-19 years of age from whom
      yearly data on caries and tobacco use (cigarette smoking and use of smokeless
      tobacco) were obtained during the period 2006-2012. Reported DMFS increment
      between 16 and 19 years of age (?DMFS) for an individual was considered as the
      primary caries outcome. The outcome data were compared for self-reported never
      vs. ever users of tobacco, with consideration to neighborhood-level socio-economy
      (4 strata), baseline (i.e., 16 years of age) DMFS and sex. The region consists of
      65 parishes with various socio-economic conditions and each study individual was
      geo-coded with respect to his/her residence parish. Neighborhood (parish-level)
      socio-economy was assessed by proportion of residing families with low household
      purchasing power. RESULTS: ?DMFS differed evidently between ever and never users
      of tobacco (mean values: 1.8 vs. 1.2; proportion with ?DMFS > 0: 54.2% vs. 40.5%;
      p < 0.0001). Significant differences were observed in each neighborhood-level
      socio-economic stratum. Even after controlling for baseline DMFS and sex, ?DMFS
      differed highly significantly between the ever and never users of tobacco
      (overall p < 0.0001). CONCLUSION: Tobacco use was clearly associated with
      increased caries increment during adolescence. Hence, this factor is relevant to
      consider in the clinical caries risk assessment of the individual patient as well
      as for community health plans dealing with oral health.

PMID- 23855640
TI  - Clinical, radiographic, ultrasonographic and computed tomographic features of
      nonseptic osteitis of the axial border of the proximal sesamoid bones.
AB  - REASONS FOR PERFORMING STUDY: Lysis of the axial aspect of equine proximal
      sesamoid bones (PSBs) is a rare condition reported to have septic or traumatic
      origins. Limited information exists regarding imaging of nonseptic axial osteitis
      of a PSB. OBJECTIVES: To report the clinical, radiographic, ultrasonographic,
      computed tomographic and intra-arterial contrast-enhanced computed tomographic
      abnormalities in horses with axial nonseptic osteitis of a PSB. STUDY DESIGN:
      Retrospective clinical study. METHODS: Eighteen horses diagnosed with nonseptic
      osteitis of the axial border of a PSB between 2007 and 2012 were reviewed
      retrospectively. Case details, clinical examination, radiographic,
      ultrasonographic, computed tomographic and intra-arterial/intra-articular
      contrast-enhanced computed tomographic features were recorded, when available.
      Radiographic, ultrasonographic and computed tomographic evaluations of the
      fetlock region had been performed on 18, 15 and 9 horses, respectively. The
      effect of the degree of lysis on the grade and duration of lameness was
      determined. RESULTS: All horses had chronic unilateral lameness, 4 with forelimb
      and 14 with hindlimb signs. On radiographs, lysis was identified in both PSBs in
      14 horses, one PSB in 3 horses and in one horse no lysis was identified. The
      degree of osteolysis was variable. Ultrasonography identified variably sized
      irregularities of the bone surface and alteration in echogenicity of the
      palmar/plantar ligament (PL). All horses undergoing computed tomographic
      examination (n = 9) had biaxial lysis. The lesions were significantly longer and
      deeper on computed tomographic images compared with radiographic images. Intra
      arterial contrast-enhanced computed tomography may reveal moderate to marked
      contrast enhancement of the PL. There was no significant effect of the degree of
      lysis on the grade and duration of lameness. CONCLUSIONS: Lesions of nonseptic
      axial osteitis of a PSB can be identified using a combination of radiography and
      ultrasonography. Computed tomography provides additional information regarding
      the extent of the pathology.

PMID- 23855641
TI  - Confidence-weighted testing: a descriptive study of Japanese nursing students.
AB  - Nurses' lack of self-confidence in their own nursing skills is one of the main
      reasons that novice nurses leave the profession in Japan. Nursing education must
      help students gain self-confidence in their nursing skills in order to allow more
      novice nurses to stay in their profession. In this study, we evaluated whether
      confidence-weighted testing feedback actually improves students' self-confidence
      in their basic nursing skills. Confidence-weighted testing, which provides
      quantifiable results, might allow students to objectively assess their skill
      related self-confidence. Sixty-seven first-year nursing students took two
      confidence-rating examinations on the knowledge and practical skills related to
      pulse and blood pressure measurement of immobile patients. Feedback was given to
      each participant after the first examination. After the first examination with
      confidence-weighted testing feedback, students showed higher levels of self
      confidence in their practical skills, but not in knowledge. The improvement of
      self-confidence in practical skills suggests that there is still room for
      improvement in confidence-weighted testing feedback in knowledge. Further
      research is required to identify more effective feedback methods to improve
      students' self-confidence levels in knowledge using the results of confidence
      weighted testing. 

PMID- 23855642
TI  - Strongyloidiasis complicating immunosuppression for pemphigus vulgaris.

PMID- 23855643
TI  - Immediate Placement and Provisionalization of Implants Into Sites With
      Periradicular Infection With and Without Antibiotics: An Exploratory Study.
AB  - This study explored the necessity of perioperative antibiotics on survival rates
      of implants immediately placed and provisionalized into sites with infection.
      Subjects were randomly assigned into antibiotic or placebo groups. Extraction,
      immediate placement, and provisionalization of an implant were performed. Eight
      subjects received placebo and five subjects received both a pre- and post
      operative antibiotic regimen. One implant from each group failed. Perioperative
      antibiotic therapy may not be needed in selected immediate implant therapy. 

PMID- 23855644
TI  - Effect of chain length of PEO on the gelation and micellization of the pluronic
      F127 copolymer aqueous system.
AB  - The effect of adding homopolymer poly(ethylene oxide) (PEO) on the sol/gel
      behavior of amphiphilic triblock copolymer Pluronic F127 ((EO)98(PO)67(EO)98) in
      aqueous media is explored. Emphasis is placed on the influence of the PEO
      molecular weight and concentration on micellization and gelation and the
      exploration of their correlation. PEO is always found to lower the critical
      micellization temperature modestly. However, short PEO chains promote the
      gelation of F127, and long chains delay or even curb gel formation. Micelle size
      measurements and cryo-TEM micrographs provide evidence for micellar aggregation
      via the bridging of long PEO chains or depletion flocculation, thereby impeding
      the ordering of micelles for gel formation. 

PMID- 23855645
TI  - Negative pressure wound therapy as an adjunct in healing of chronic wounds.
AB  - Negative pressure wound therapy (NPWT) has emerged as a cutting-edge technology
      and provides an alternative solution to the problem of wounds. This study was
      undertaken to assess the efficacy of this technique in the treatment of chronic
      wounds. A prospective clinical study was used to evaluate our experience in use
      of NPWT in the healing of pressure ulcers and chronic wounds over 2 years. The
      primary end point of the study group was the time taken for appearance of healthy
      granulation tissue and full reepithelialisation without drainage. All patients
      with sepsis were excluded from the study. The statistical analysis of the data
      was carried out. Of the 60 patients studied, 41 had associated comorbidities
      including diabetes mellitus. The commonest site of occurrence was the lower limb.
      Coverage in the form of a flap was required at presentation in 63.33% of
      patients. However, after initiation of NPWT, none of them required the procedure
      and they healed spontaneously either by secondary intention or by skin grafting.
      The time taken for appearance of healthy granulation tissue was 14.36 +/- 4.24
      days. Complete healing of wounds occurred by 33.1 +/- 10.22 days. There was a
      statistically significant difference in the volume of the wounds before and after
      the intervention (P = 0.000). Complications resulting from NPWT were minimal.
      This technique is an excellent adjunct to surgical debridement. 

PMID- 23855646
TI  - Serum albumin levels and 10-year tooth loss in a 70-year-old population.
AB  - Serum albumin levels are a practical marker of general health status in the
      elderly and have been used to determine the severity of underlying diseases and
      the risk for death. This longitudinal study evaluated the relationship between
      serum albumin concentrations and tooth loss over 10 years in elderly subjects,
      after controlling for confounding factors. A sample of 554 dentate subjects among
      enrolled subjects (n = 600) was involved in this planned longitudinal study with
      follow-up examinations after 5 and 10 years. At the 5-year follow-up, 373
      (67.3%), subjects were available for re-examination. In addition, 331 (59.7%)
      were available at the 10-year follow-up. Multiple Poisson regression analysis was
      conducted to evaluate the relationship between the number of missing teeth over 5
      or 10 years and serum albumin levels at baseline after adjusting for 10
      variables: gender, serum markers levels at baseline, dental status, smoking
      habits and educational years and oral health behaviour. The number of missing
      teeth over 5 or 10 years was significantly negatively associated with serum
      albumin levels at baseline [incidence rate ratios (IRR) = 0.373, P < 0.0001 for 5
      years; IRR = 0.570, P < 0.0001 for 10 years]. We conclude that elderly subjects
      with hypoalbuminemia are at high risk for 5- and 10-year tooth loss.

PMID- 23855647
TI  - Knowledge from data in the built environment.
AB  - Data feedback is changing our relationship to the built environment. Both
      traditional and new sources of data are developing rapidly, compelled by efforts
      to optimize the performance of human habitats. However, there are many obstacles
      to the successful implementation of information-centered environments that
      continue to hinder widespread adoption. This paper identifies these obstacles and
      challenges and describes emerging data-rich analytic techniques in
      infrastructure, buildings, and building portfolios. Further, it speculates on the
      impact that a robust data sphere may have on the built environment and posits
      that linkages to other data sets may enable paradigm shifts in sustainability and
      resiliency. 

PMID- 23855648
TI  - Combination of injection volume calibration by creatinine and MS signals'
      normalization to overcome urine variability in LC-MS-based metabolomics studies.
AB  - It is essential to choose one preprocessing method for liquid chromatography-mass
      spectrometry (LC-MS)-based metabolomics studies of urine samples in order to
      overcome their variability. However, the commonly used normalization methods do
      not substantially reduce the high variabilities arising from differences in urine
      concentration, especially for signal saturation (abundant metabolites exceed the
      dynamic range of the instrumentation) or missing values. Herein, a simple
      preacquisition strategy based on differential injection volumes calibrated by
      creatinine (to reduce the concentration differences between the samples),
      combined with normalization to "total useful MS signals" or "all MS signals", is
      proposed to overcome urine variabilities. This strategy was first systematically
      compared with other popular normalization methods by application to serially
      diluted urine samples. Then, the method has been verified using rat urine samples
      of pre- and postinoculation of Walker 256 carcinoma cells. The results showed
      that the calibration of injection volumes based on creatinine values could
      effectively eliminate intragroup differences caused by variations in the
      concentrations of urinary metabolites, thus giving better parallelism and
      clustering effects. In addition, peak area normalization could further eliminate
      intraclass differences. Therefore, the strategy of combining peak area
      normalization with calibration of injection volumes of urine samples based on
      their creatinine values is effective for solving problems associated with urinary
      metabolomics. 

PMID- 23855649
TI  - Identification of metabolic pathways in Daphnia magna explaining hormetic effects
      of selective serotonin reuptake inhibitors and 4-nonylphenol using transcriptomic
      and phenotypic responses.
AB  - The molecular mechanisms explaining hormetic effects of selective serotonin
      reuptake inhibitors (SSRIs) and 4-nonylphenol in Daphnia magna reproduction were
      studied in juveniles and adults. Transcriptome analyses showed changes in mRNA
      levels for 1796 genes in juveniles and 1214 genes in adults (out of 15000 total
      probes) exposed to two SSRIs (fluoxetine and fluvoxamine) or to 4-nonylphenol.
      Functional annotation of affected genes was improved by assuming the annotations
      of putatively homologous Drosophila genes. Self-organizing map analysis and
      partial least-square regression coupled with selectivity ratio procedures
      analyses allowed to define groups of genes with specific responses to the
      different treatments. Differentially expressed genes were analyzed for functional
      enrichment using Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes
      databases. Serotonin metabolism, neuronal developmental processes, and
      carbohydrates and lipid metabolism functional categories appeared as selectively
      affected by SSRI treatment, whereas 4-nonylphenol deregulated genes from the
      carbohydrate metabolism and the ecdysone regulatory pathway. These changes in
      functional and metabolic pathways are consistent with previously reported SSRIs
      and 4-nonylphenol hormetic effects in D. magna, including a decrease in reserve
      carbohydrates and an increase in respiratory metabolism.

PMID- 23855650
TI  - Population-based incidence estimates of influenza-associated respiratory failure
      hospitalizations, 2003 to 2009.
AB  - RATIONALE: The incidence of influenza-associated acute respiratory failure is
      unknown. OBJECTIVES: To estimate the population-based incidence of influenza
      associated acute respiratory failure hospitalizations. METHODS: This is a cohort
      study from January 2003 through March 2009 using hospitalization databases for
      Arizona, California, and Washington from the Healthcare Cost and Utilization
      Project and influenza surveillance data for regions encompassing these states.
      Acute respiratory failure requiring mechanical ventilation was defined by
      International Classification of Diseases-9-CM code. We used negative-binomial
      regression modeling to estimate the incidence of influenza-associated events.
      MEASUREMENTS AND MAIN RESULTS: The incidence of influenza-associated acute
      respiratory failure was 2.7 per 100,000 person-years (95% confidence interval,
      0.2-23.5), and during the influenza season, 3.8% of all respiratory failure
      hospitalizations were attributable to influenza. Compared with adults aged 18-49
      years, the incidence rate ratio for influenza-associated acute respiratory
      failure was lower among children aged 1-4 (0.9) and 5-17 years (0.3); however, it
      was higher among adults aged 50-64 (4.8), 65-74 (10.4), 75-84 (19.9), and 85
      years and older (33.7). Results were similar with more sensitive and specific
      outcome definitions and in a sensitivity analysis using only Arizona-specific
      outcome and surveillance data. CONCLUSIONS: Our data indicate that influenza was
      an important contributor to respiratory failure hospitalizations during 2003
      2009. Clinicians should maintain a high index of suspicion for influenza among
      hospitalized patients with acute respiratory illness when influenza is
      circulating in a community. Influenza has a greater effect on respiratory failure
      in the elderly, for whom better prevention measures are needed.

PMID- 23855651
TI  - Speech disturbance at stroke onset is correlated with stroke early mortality.
AB  - BACKGROUND: Speech disturbance is a common symptom of stroke and is important as
      a prompt identifier of the event. The frequency of the symptom among each stroke
      subtype, differences between patients with and without speech disturbance and its
      correlation to early mortality remain unclear. METHODS: The Kyoto prefecture of
      Japan has established a registry to enroll new stroke patients in cooperation
      with the Kyoto Medical Association and its affiliated hospitals. It is named the
      Kyoto Stroke Registry (KSR). We confirmed the existence or absence of speech
      disturbance in 1693 stroke patients registered to the KSR and investigated
      associations between speech disturbance and other characteristics. RESULTS:
      Speech disturbance was observed in 52.6% of cerebral infarction (CI), 47.5% of
      cerebral hemorrhage (CH), and 8.0% of subarachnoid hemorrhage (SAH) cases.
      Characteristics showing statistically significant differences between patients
      with and without speech disturbance and patients were age, blood pressure,
      history of hypertension, arrhythmia and diabetes mellitus, habit of tobacco and
      alcohol, and paresis. Mortality rates of patients with/without speech disturbance
      were 5.2%/1.2% for CI, 12.5% /4.1% for CH, and 62.5%/ 9.0% for SAH. Adjusted
      hazard ratios were 2.63 (1.14-6.13, p = 0.024) in CI, 4.15 (1.41-12.23, p =
      0.010) in CH, and 20.46 (4.40-95.07, p < 0.001) in SAH). CONCLUSION: Speech
      disturbance was frequently observed in stroke patients at the onset and therefore
      could be useful to identify the problem at the earliest stage. Hazard ratio for
      death was higher in stroke patients with speech disturbance than patients
      without. Speech disturbance is a prompt predictor of stroke early
      mortality.Hiromi Nakano, Yoshiyuki Watanabe, Tatsuyuki Sekimoto, Kouichiro
      Shimizu, Akihiko Nishizawa, Atsushi Okumura and Masahiro Makino contributed
      equally to this work.

PMID- 23855652
TI  - Effect of ubiquinol-10 on citral stability and off-flavor formation in oil-in
      water (O/W) nanoemulsions.
AB  - The effects of different concentrations of ubiquinol-10 (Q10H2) on citral's
      stability were systematically investigated and compared in citral-loaded oil-in
      water (O/W) nanoemulsions. Solid phase microextraction gas chromatography (SPME
      GC) was employed to monitor the degradation of citral and the formation of off
      flavor compounds throughout storage at 25 and 45  degrees C. The optimum
      concentration of Q10H2 in the current formulation was determined to be around
      0.10 wt % in the system (Q10H2/citral ratio 1:1), which can effectively protect
      citral from chemical degradation and oxidation. Results suggested, however, that
      a low concentration of Q10H2 may induce the majority of the ubisemiquinone (Q10(*
      ))/ubiquinone (Q10) redox transition, which possibly endowed Q10H2 with pro
      oxidant properties. Further increase in Q10H2 concentration beyond a certain
      value also hindered its effect due to the complex properties of radicals involved
      and the overall environment encountered. With appropriate concentrations of Q10H2
      presented in the system, major citral oxidation off-flavor compounds (p-cresol,
      alpha,p-dimethylstyrene, p-methylacetophenone), and some of the lipid degradation
      products can be inhibited to lower levels. In contrast, ubiquinone-10 (Q10) had a
      negligible effect on citral's chemical stability and off-flavor generation. 

PMID- 23855654
TI  - Prevalence of asteatosis and asteatotic eczema among elderly residents in
      facilities covered by long-term care insurance.

PMID- 23855653
TI  - A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to
      study the safety of the adipose derived stromal cells-stromal vascular fraction
      in idiopathic pulmonary fibrosis.
AB  - INTRODUCTION: Regenerative medicine and particular adult stem cells represent an
      alternative option with several fruitful therapeutic applications in patients
      suffering from chronic lung diseases including idiopathic pulmonary fibrosis
      (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of
      mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their
      use for the treatment of this dismal disease. PATIENTS AND METHODS: To this end,
      we conducted a phase Ib, non-randomized, clinical trial to study the safety of
      three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)
      stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per
      infusion) in patients with IPF (n=14) of mild to moderate disease severity
      (forced vital capacity -FVC>50% predicted value and diffusion lung capacity for
      carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence
      of treatment emergent adverse events within 12 months. Alterations of functional,
      exercise capacity and quality of life parameters at serial time points (baseline,
      6 and 12 months after first infusion) were exploratory secondary end-points.
      RESULTS: No cases of serious or clinically meaningful adverse events including
      short-term infusional toxicities as well as long-term ectopic tissue formation
      were recorded in all patients. Detailed safety monitoring through several time
      points indicated that cell-treated patients did not deteriorate in both
      functional parameters and indicators of quality of life. CONCLUSIONS: The
      clinical trial met its primary objective demonstrating an acceptable safety
      profile of endobronchially administered autologous ADSCs-SVF. Our findings
      accelerate the rapidly expanded scientific knowledge and indicate a way towards
      future efficacy trials.

PMID- 23855655
TI  - A decision theory paradigm for evaluating identifier mapping and filtering
      methods using data integration.
AB  - BACKGROUND: In bioinformatics, we pre-process raw data into a format ready for
      answering medical and biological questions. A key step in processing is labeling
      the measured features with the identities of the molecules purportedly assayed:
      "molecular identification" (MI). Biological meaning comes from identifying these
      molecular measurements correctly with actual molecular species. But MI can be
      incorrect. Identifier filtering (IDF) selects features with more trusted MI,
      leaving a smaller, but more correct dataset. Identifier mapping (IDM) is needed
      when an analyst is combining two high-throughput (HT) measurement platforms on
      the same samples. IDM produces ID pairs, one ID from each platform, where the
      mapping declares that the two analytes are associated through a causal path,
      direct or indirect (example: pairing an ID for an mRNA species with an ID for a
      protein species that is its putative translation). Many competing solutions for
      IDF and IDM exist. Analysts need a rigorous method for evaluating and comparing
      all these choices. RESULTS: We describe a paradigm for critically evaluating and
      comparing IDF and IDM methods, guided by data on biological samples. The
      requirements are: a large set of biological samples, measurements on those
      samples from at least two high-throughput platforms, a model family connecting
      features from the platforms, and an association measure. From these ingredients,
      one fits a mixture model coupled to a decision framework. We demonstrate this
      evaluation paradigm in three settings: comparing performance of several
      bioinformatics resources for IDM between transcripts and proteins, comparing
      several published microarray probeset IDF methods and their combinations, and
      selecting optimal quality thresholds for tandem mass spectrometry spectral
      events. CONCLUSIONS: The paradigm outlined here provides a data-grounded approach
      for evaluating the quality not just of IDM and IDF, but of any pre-processing
      step or pipeline. The results will help researchers to semantically integrate or
      filter data optimally, and help bioinformatics database curators to track changes
      in quality over time and even to troubleshoot causes of MI errors.

PMID- 23855656
TI  - Is living donor liver transplantation really equivalent to deceased donor liver
      transplantation?

PMID- 23855657
TI  - Risk factors for acute renal injury in living donor liver transplantation:
      evaluation of the RIFLE criteria.
AB  - Acute renal injury (ARI) is a serious complication after liver transplantation.
      This study investigated the usefulness of the RIFLE criteria in living donor
      liver transplantation (LDLT) and the prognostic impact of ARI after LDLT. We
      analyzed 200 consecutive adult LDLT patients, categorized as risk (R), injury
      (I), or failure (F), according to the RIFLE criteria. ARI occurred in 60.5% of
      patients: R-class, 23.5%; I-class, 21%; and F-class, 16%. Four patients in Group
      A (normal renal function and R-class) and 26 patients in Group-B (severe ARI: I-
      and F-class) required renal replacement therapy (P < 0.001). Mild ARI did not
      affect postoperative prognosis regarding hospital mortality rate in Group A
      (3.2%), which was superior to that in Group B (15.8%; P = 0.0015). Fourteen
      patients in Group B developed chronic kidney disease (KDIGO stage 3/4). The 1-, 5
      and 10-year survival rates were 96.7%, 90.6%, and 88.1% for Group A and 71.1%,
      65.9%, and 59.3% for Group B, respectively (P < 0.0001). Multivariate analysis
      revealed risk factors for severe ARI as MELD >= 20 [odds ratio (OR) 2.9], small
      for-size graft (GW/RBW <0.7%; OR 3.1), blood loss/body weight >55 ml/kg (OR 3.7),
      overexposure to calcineurin inhibitor (OR 2.5), and preoperative diabetes
      mellitus (OR 3.2). The RIFLE criteria offer a useful predictive tool after LDLT.
      Severe ARI, defined beyond class-I, could have negative prognostic impact in the
      acute and late postoperative phases. Perioperative treatment strategies should be
      designed and balanced based on the risk factors for the further improvement of
      transplant prognosis.

PMID- 23855658
TI  - Protein-protein interactions and prediction: a comprehensive overview.
AB  - Molecular function in cellular processes is governed by protein-protein
      interactions (PPIs) within biological networks. Selective yet specific
      association of these protein partners contributes to diverse functionality such
      as catalysis, regulation, assembly, immunity, and inhibition in a cell.
      Therefore, understanding the principles of protein-protein association has been
      of immense interest for several decades. We provide an overview of the
      experimental methods used to determine PPIs and the key databases archiving this
      information. Structural and functional information of existing protein complexes
      confers knowledge on the principles of PPI, based on which a classification
      scheme for PPIs is then introduced. Obtaining high-quality non-redundant datasets
      of protein complexes for interaction characterisation is an essential step
      towards deciphering their underlying binding principles. Analysis of
      physicochemical features and their documentation has enhanced our understanding
      of the molecular basis of protein-protein association. We describe the diverse
      datasets created/collected by various groups and their key findings inferring
      distinguishing features. The currently available interface databases and
      prediction servers have also been compiled. 

PMID- 23855659
TI  - Amylin conjugation with methoxyl polyethyleneglycol.
AB  - We modified amylin chemically by conjugating methoxyl polyethyleneglycol
      succinimidyl carbonate (mPEGSC) of varying molecular weights (1 kDa, 2 kDa and 5
      kDa). The reaction occurred within a few minutes, resulting in at least four
      distinct PEGylated products. The reaction products were separated by reversed
      phase chromatography and identified by mass-spectrometry. The monoPEGylated and
      diPEGylated amylin products were generated rapidly through conjugation to the two
      amino groups of the N-terminal lysine residue. Both PEGylated amylin products
      bound to the receptor activity-modifying protein 1 (RAMP1). Pharmacological
      evaluation by subcutaneous administration in mice of monoPEGylated and
      diPEGylated amylin obtained with mPEG-SC 5 kDa revealed that both compounds
      modulated glycemia for longer times than unmodified amylin. Collectively, these
      data demonstrate the potential of bioconjugation with mPEG for the design of
      amylin therapeutics with sustained action. 

PMID- 23855660
TI  - Precursor mass dependent filtering of mass spectra for proteomics analysis.
AB  - Identification and elimination of noise peaks in mass spectra from large
      proteomics data streams simultaneously improves the accuracy of peptide
      identification and significantly decreases the size of the data. There are a
      number of peak filtering strategies that can achieve this goal. Here we present a
      simple algorithm wherein the number of highest intensity peaks retained for
      further analysis is proportional to the mass of the precursor ion. We show that
      this technique provides an improvement over other intensity based strategies,
      especially for low mass precursors. 

PMID- 23855661
TI  - SVM-PB-Pred: SVM based protein block prediction method using sequence profiles
      and secondary structures.
AB  - We developed a support vector machine based web server called SVM-PB-Pred, to
      predict the Protein Block for any given amino acid sequence. The input features
      of SVM-PB-Pred include i) sequence profiles (PSSM) and ii) actual secondary
      structures (SS) from DSSP method or predicted secondary structures from NPS@ and
      GOR4 methods. There were three combined input features PSSM+SS(DSSP),
      PSSM+SS(NPS@) and PSSM+SS(GOR4) used to test and train the SVM models. Similarly,
      four datasets RS90, DB433, LI1264 and SP1577 were used to develop the SVM models.
      These four SVM models developed were tested using three different benchmarking
      tests namely; (i) self consistency, (ii) seven fold cross validation test and
      (iii) independent case test. The maximum possible prediction accuracy of ~70% was
      observed in self consistency test for the SVM models of both LI1264 and SP1577
      datasets, where PSSM+SS(DSSP) input features was used to test. The prediction
      accuracies were reduced to ~53% for PSSM+SS(NPS@) and ~43% for PSSM+SS(GOR4) in
      independent case test, for the SVM models of above two same datasets. Using our
      method, it is possible to predict the protein block letters for any query protein
      sequence with ~53% accuracy, when the SP1577 dataset and predicted secondary
      structure from NPS@ server were used. The SVM-PB-Pred server can be freely
      accessed through http://bioinfo.bdu.ac.in/~svmpbpred. 

PMID- 23855662
TI  - Biomedical hypothesis generation by text mining and gene prioritization.
AB  - Text mining methods can facilitate the generation of biomedical hypotheses by
      suggesting novel associations between diseases and genes. Previously, we
      developed a rare-term model called RaJoLink (Petric et al, J. Biomed. Inform.
      42(2): 219-227, 2009) in which hypotheses are formulated on the basis of terms
      rarely associated with a target domain. Since many current medical hypotheses are
      formulated in terms of molecular entities and molecular mechanisms, here we
      extend the methodology to proteins and genes, using a standardized vocabulary as
      well as a gene/protein network model. The proposed enhanced RaJoLink rare-term
      model combines text mining and gene prioritization approaches. Its utility is
      illustrated by finding known as well as potential gene-disease associations in
      ovarian cancer using MEDLINE abstracts and the STRING database. 

PMID- 23855663
TI  - Design and docking studies of peptide inhibitors as potential antiviral drugs for
      dengue virus ns2b/ns3 protease.
AB  - Dengue virus (DENV), one of the members of genus Flavivirus is emerging as a
      global threat to human health. It had led to the emergence of dengue fever (flu
      like illness), dengue shock syndrome, and the most severe dengue hemorrhagic
      fever (severe dengue with bleeding abnormalities). As Dengue hemorrhage diseases
      are the life-threatening ones, attempts are being made worldwide to design
      inhibitors for DENV-2 NS2B-NS3 protease. NS2B/NS3 protease plays a vital role in
      the replication of dengue virus. The trypsin-like serine protease domain of NS3
      contains the functional catalytic triad His-51, Asp-75, and Ser-135 in the N
      terminal region. Inhibition of the NS3 protease activity is expected to prevent
      the propagation of dengue virus. Current drug discovery methods are largely
      inefficient and thus relatively ineffective in tackling the growing threat to
      public health presented by emerging and remerging viral pathogens. Recently,
      there has been a need of interest in peptides and their mimetics as potential
      antagonists for dengue protease because these small peptides are unlikely to
      invoke an immune response since they fall below the immunogenic threshold. They
      are often potent and display fewer toxicity issues than small-molecule compounds
      as a result of high specificity. This study was conducted to design peptides as
      enzyme inhibitors of dengue virus NS3 protease through computational approach.
      Crystallographic structure of dengue protease was retrieved from Protein Data
      Bank (PDBID: 2FOM) and docked with the peptides and the results are analyzed.
      From the docking studies reported in this paper, tetrapeptide (Lys-Gly-Pro-Glu),
      pentapeptide (Ser-Ile-Lys-Phe-Ala) and hexapeptide (Ala-Ile-Lys-Lys-Phe-Ser) with
      glide energy -70.0 kcal/mol, -72.2 kcal/mol and - 80.4 kcal/mol respectively show
      promising results which can be considered for further optimization and in vitro
      studies. 

PMID- 23855664
TI  - Identification of ligand binding pockets on nuclear receptors by machine learning
      methods.
AB  - Nuclear receptors constitute a super family of protein hormones that serve as
      transcription factors. They typically reside in the cytosol and, after ligand
      binding, migrate to the nucleus to exert their biological action. Ligands are
      lipophilic, small molecules including retinoids, steroids, thyroxine, and vitamin
      D. Nuclear receptors being important regulators of gene expression, constitute
      13% of proteins targeted by various drugs. Thus it becomes important to identify
      the ligand binding pockets on these proteins. Support Vector Machine (SVM)
      classifier was built to identify nuclear receptor ligand binding pockets.
      Positive dataset consisted of the ligand binding pockets of known nuclear
      receptor-ligand complex structures. Negative dataset consisted of ligand binding
      pockets of proteins other than nuclear receptors and nonligand binding pockets of
      nuclear receptors. SVM model yielded a 10 fold cross-validation accuracy of 96%
      using linear kernel. Also, it is helpful to find out the class of nuclear
      receptor in order to design a "class-specific" drug. In case of the multiclass
      nuclear receptor dataset comprising of nuclear receptors belonging to three
      different classes, SVM model for classification yielded an average 10-fold cross
      validation accuracy of 92 % for this dataset. SVM algorithm identifies and
      classifies nuclear receptor binding pockets with excellent accuracy. Top ranked
      features indicate the hydrophobic nature of ligand binding pocket of nuclear
      receptors. Conserved Leucine and phenylalanine residues form a distinguishing
      feature of these binding pockets. Along-with identification of NR binding
      pockets, important top ranked features are listed which would be useful in
      screening of possible drug molecules with NRs as molecular targets. 

PMID- 23855665
TI  - Structure function analysis of serpin super-family: "a computational approach".
AB  - Serine Protease inhibitors (serpins) are a super-family of proteins that controls
      the proteinases involved in the inflammation, complementation, coagulation and
      fibrinolytic pathways. Serpins are prone to conformational diseases due to a
      complex inhibition mechanism that involves large scale conformational change, and
      their susceptibility to undergo point mutations might lead to functional defects.
      Serpins are associated with diseases like emphysema/cirrhosis, angioedema,
      familial dementia, chronic obstructive bronchitis and thrombosis. Serpin
      polymerization based pathologies are fairly widespread and devising a cure has
      been difficult due to lack of clarity regarding its mechanism. Serpin can exist
      in various conformational states and has a variable cofactor binding ability. It
      has a large genome and proteome database which can be utilized to gain critical
      insight into their structure, mechanism and defects. Comprehensive computational
      studies on the serpin family is lacking, most of the work done till date is
      limited and deals mostly with few individual serpins. We have tried to analyze
      few aspect of this family using diverse computational biology tools and have
      shown the following: a) the importance of residue burial linked shift in the
      conformational stability as a major factor in increasing the polymer propensity
      in serpins. b) Amino acids involved in the polymerization are in general
      completely buried in the native conformation. c) An isozyme specific antithrombin
      study showed the structural basis of improved heparin binding to beta
      antithrombin as compared to alpha-antithrombin. d) A comprehensive cavity
      analysis showed its importance in inhibition and polymerizaiton and finally e) an
      interface analysis of various serpin protease complexes identified critical
      evolutionary conserved residues in exosite that determines its protease
      specificity. This work introduces the problem and emphasizes on the need for in
      depth computational studies of serpin superfamily. 

PMID- 23855666
TI  - Structural-functional integrity of hypothetical proteins identical to
      ADPribosylation superfamily upon point mutations.
AB  - In the present study, we have evaluated the impacts of point mutations on
      structural and functional evolution of hypothetical proteins identical to
      bacterial ADP-ribosylation superfamily members using bioinformatics approaches. A
      combined approach of molecular modelling and dynamics was employed to generate
      energetically stable structures from hypothetical protein sequences. Improper
      energy and structural constraints of the resulted homology models were stabilized
      by molecular dynamic simulation and hybrid Monte Carlo approaches. Since amino
      acid substitutions occurring in highly mutable functional sites, catalytic
      activity or substrate specificity would be expected to adjust without
      compromising their structural stability. In silico mutagenesis studies showed
      that protein structural stability has not been changed upon point mutations, but
      functional firmness has modified unusually from virulence to avirulence. Protein
      variants such as BTA3V10 (Gly(421)->Val(421)), BTA3V11 (Gly(421)->Leu(421)),
      BTA3V17 (Gly(422)->Phe(422)) and PTS15V1 (Cys(26)->Met(26)) and PTS15V2 (Cys(26)
      >Thy(26)) generated from this study showed to have a fast fold rate and stable
      energetic structures compared to wild type proteins. Overall, structures and
      functional integrity of the hypothetical proteins were identical to the members
      in bacterial ADP-ribosylation superfamily. A catalytic activity of ADP
      ribosyltransferase existing in the hypothetical proteins would determine whether
      virulent state or avirulent state by deleterious mutations occurring in the
      subdynamic space of a conserved domain. 

PMID- 23855667
TI  - Laccase enzymes: purification, structure to catalysis and tailoring.
AB  - Laccases belong to the multicopper binding protein family that catalysis the
      reduction of oxygen molecule to produce water. These enzymes are glycosylated
      proteins and have been isolated and purified from fungi, bacteria, plant, insects
      and lichens. The variety of commercial and industrial application of laccases has
      attracted much attention towards the research addressing different aspects of the
      protein characterization, production and fit for purpose molecule. Here we
      briefly discuss the purification, catalytic mechanism in light of available
      understanding of structure-function relationship and the tailoring side of the
      protein, which has been the subject of recent research. Purification strategy of
      laccases is a method of choice and is facilitated by increased production of the
      enzyme. The structure-function relationship has given insights to unfold the
      catalytic mechanism. Site directed mutagenesis and other modification at C
      terminal end or surrounding environment of copper centres have shown promising
      results to fit for purpose aspect, with a lot remains to be explored in
      glycosylation status and its alteration. 

PMID- 23855668
TI  - Rho Kinase Inhibitors and Novel Ocular Drug Delivery Systems- A Revolutionary
      Step Towards the Treatment of Glaucoma.
AB  - BACKGROUND: Glaucoma is an ocular disorder characterized by optic nerve damage
      which ultimately causes a progressive and an irreversible loss of vision, often
      characterized by an elevated intraocular pressure. Lowering the intraocular
      pressure (IOP) is the mainstay for glaucoma treatment but the neuroprotective
      agents would represent a promising class as the next-generation therapy. EVIDENCE
      SYNTHESIS: Protein kinases are involved considerably in signal transduction
      pathways confirmed by various mechanisms giving the evidence of Rho-kinase to be
      a versatile therapeutic target. Rho associated protein kinases also known as ROCK
      are serine/threonine kinases, belonging to the Ras superfamily of GTPases. The
      activation of Rho Kinase results in various actin-myosin arbitrated processes
      where contraction of actomyosin in the resident trabecular meshwork (TM) cells
      and extracellular matrix is responsible for the outflow of aqueous humour.
      Another major drawback of the currently available antiglaucoma drugs is their
      topical use which poses a problem for patient compliance. The patient
      intolerability and adherence to the existing therapy therefore call for newer
      drug delivery systems that would increase the clinical efficacy of the drugs.
      CONCLUSION: The neuroprotective agents are not considered suitable to be
      administered through the traditional topical or oral route. This complementary
      drug therapy requires a delivery system that could release the drug to the optic
      nerve in a sustained manner and also increase patient compliance and
      tolerability. This review summarizes the use of ROCK inhibitors that could
      prevent the damage to the optic nerve along with the reduction in IOP and novel
      drug delivery systems to increase the efficacy of the drugs.

PMID- 23855669
TI  - Protein-protein interaction network prediction by using rigid-body docking tools:
      application to bacterial chemotaxis.
AB  - Core elements of cell regulation are made up of protein-protein interaction (PPI)
      networks. However, many parts of the cell regulatory systems include unknown
      PPIs. To approach this problem, we have developed a computational method of high
      throughput PPI network prediction based on all-to-all rigid-body docking of
      protein tertiary structures. The prediction system accepts a set of data
      comprising protein tertiary structures as input and generates a list of possible
      interacting pairs from all the combinations as output. A crucial advantage of
      this docking based method is in providing predictions of protein pairs that
      increases our understanding of biological pathways by analyzing the structures of
      candidate complex structures, which gives insight into novel interaction
      mechanisms. Although such exhaustive docking calculation requires massive
      computational resources, recent advancements in the computational sciences have
      made such large-scale calculations feasible. In this study we applied our
      prediction method to a pathway reconstruction problem of bacterial chemotaxis by
      using two different rigid-body docking tools with different scoring models. We
      found that the predicted interactions were different between the results from the
      two tools. When the positive predictions from both of the docking tools were
      combined, all the core signaling interactions were correctly predicted with the
      exception of interactions activated by protein phosphorylation. Large-scale PPI
      prediction using tertiary structures is an effective approach that has a wide
      range of potential applications. This method is especially useful for identifying
      novel PPIs of new pathways that control cellular behavior. 

PMID- 23855670
TI  - Mapping and annotating obesity-related genes in pig and human genomes.
AB  - Background. Obesity is a major health problem in both developed and emerging
      countries. Obesity is a complex disease whose etiology involves genetic factors
      in strong interplay with environmental determinants and lifestyle. The discovery
      of genetic factors and biological pathways underlying human obesity is hampered
      by the difficulty in controlling the genetic background of human cohorts. Animal
      models are then necessary to further dissect the genetics of obesity. Pig has
      emerged as one of the most attractive models, because of the similarity with
      humans in the mechanisms regulating the fat deposition. Results. We collected the
      genes related to obesity in humans and to fat deposition traits in pig. We
      localized them on both human and pig genomes, building a map useful to interpret
      comparative studies on obesity. We characterized the collected genes structurally
      and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein
      interaction network. Conclusions. The collected set consists of 361 obesity
      related genes in human and pig genomes. All genes were mapped on the human
      genome, and 54 could not be localized on the pig genome (release 2012). Only for
      3 human genes there is no counterpart in pig, confirming that this animal is a
      good model for human obesity studies. Obesity related genes are mostly involved
      in regulation and signaling processes/pathways and relevant connection emerges
      between obesity-related genes and diseases such as cancer and infectious
      diseases. 

PMID- 23855671
TI  - Bioinformatic screening of autoimmune disease genes and protein structure
      prediction with FAMS for drug discovery.
AB  - Autoimmune diseases are often intractable because their causes are unknown.
      Identifying which genes contribute to these diseases may allow us to understand
      the pathogenesis, but it is difficult to determine which genes contribute to
      disease. Recently, epigenetic information has been considered to
      activate/deactivate disease-related genes. Thus, it may also be useful to study
      epigenetic information that differs between healthy controls and patients with
      autoimmune disease. Among several types of epigenetic information, promoter
      methylation is believed to be one of the most important factors. Here, we propose
      that principal component analysis is useful to identify specific gene promoters
      that are differently methylated between the normal healthy controls and patients
      with autoimmune disease. Full Automatic Modeling System (FAMS) was used to
      predict the three-dimensional structures of selected proteins and successfully
      inferred relatively confident structures. Several possibilities of the
      application to the drug discovery based on obtained structures are discussed. 

PMID- 23855672
TI  - Thermodynamic stability and flexibility characteristics of antibody fragment
      complexes.
AB  - Free energy landscapes, backbone flexibility and residue-residue couplings for
      being co-rigid or co-flexible are calculated from the minimal Distance Constraint
      Model (mDCM) on an exploratory dataset consisting of VL, scFv and Fab antibody
      fragments. Experimental heat capacity curves are reproduced markedly well, and an
      analysis of quantitative stability/flexibility relationships (QSFR) is applied to
      a representative VL domain and several complexes in the scFv and Fab forms.
      Global flexibility in the denatured ensemble typically decreases in the larger
      complexes due to domain-domain interfaces. Slight decreases in global flexibility
      also occur in the native state of the larger fragments, but with a concurrent
      large increase in correlated flexibility. Typically, a VL fragment has more co
      rigid residue pairs when isolated compared to the scFv and Fab forms, where
      correlated flexibility appears upon complex formation. This context dependence on
      residue- residue couplings in the VL domain across length scales of a complex is
      consistent with the evolutionary hypothesis of antibody maturation. In comparing
      two scFv mutants with similar thermodynamic stability, local and long-ranged
      changes in backbone flexibility are observed. In the case of anti-p24 HIV-1 Fab,
      a variety of QSFR metrics were found to be atypical, which includes comparatively
      greater co-flexibility in the VH domain and less co-flexibility in the VL domain.
      Interestingly, this fragment is the only example of a polyspecific antibody in
      our dataset. Finally, the mDCM method is extended to cases where thermodynamic
      data is incomplete, enabling high throughput QSFR studies on large numbers of
      antibody fragments and their complexes. 

PMID- 23855673
TI  - MEGADOCK: an all-to-all protein-protein interaction prediction system using
      tertiary structure data.
AB  - The elucidation of protein-protein interaction (PPI) networks is important for
      understanding cellular structure and function and structure-based drug design.
      However, the development of an effective method to conduct exhaustive PPI
      screening represents a computational challenge. We have been investigating a
      protein docking approach based on shape complementarity and physicochemical
      properties. We describe here the development of the protein-protein docking
      software package "MEGADOCK" that samples an extremely large number of protein
      dockings at high speed. MEGADOCK reduces the calculation time required for
      docking by using several techniques such as a novel scoring function called the
      real Pairwise Shape Complementarity (rPSC) score. We showed that MEGADOCK is
      capable of exhaustive PPI screening by completing docking calculations 7.5 times
      faster than the conventional docking software, ZDOCK, while maintaining an
      acceptable level of accuracy. When MEGADOCK was applied to a subset of a general
      benchmark dataset to predict 120 relevant interacting pairs from 120 x 120 =
      14,400 combinations of proteins, an F-measure value of 0.231 was obtained.
      Further, we showed that MEGADOCK can be applied to a large-scale protein-protein
      interaction-screening problem with accuracy better than random. When our approach
      is combined with parallel high-performance computing systems, it is now feasible
      to search and analyze protein-protein interactions while taking into account
      three-dimensional structures at the interactome scale. MEGADOCK is freely
      available at http://www.bi.cs.titech.ac.jp/megadock. 

PMID- 23855674
TI  - Allen-Masters syndrome: do the classic risk factors also apply in patients with
      endometriosis?
AB  - AIM: To evaluate whether the classic risk factors for Allen-Masters syndrome,
      such as body mass index (BMI) and spontaneous births, are in fact responsible for
      the condition in patients with endometriosis. METHODS: A total of 26 women who
      underwent a laparoscopic procedure due to chronic pelvic pain, Allen-Masters
      syndrome and endometriosis from 2009-2011 were enrolled in this study from an
      endometriosis competence center specializing in minimally invasive surgery. This
      was a retrospective cohort study (Canadian Task Force classification II-2).
      RESULTS: Only eight of the 26 patients (30.77%; 95% confidence interval [CI],
      14.33-51.79%) had the classic risk factors (BMI >25 kg/m(2) and/or at least one
      spontaneous birth). The mean age in the study group was 32.08 years (SD +/-
      5.45). The patients had a mean BMI (kg/m(2) ) of 19.61 (SD +/- 3.07). The means
      for the patients' clinical data were 0.88 (SD +/- 1.53) pregnancies, 0.81 (SD +/-
      1.23) for parity, 0.27 (SD +/- 0.60) for cesareans and 0.54 (SD +/- 0.99) for
      spontaneous births. The revised American Society for Reproductive Medicine
      (rASRM) stage showed a median of grade III. The left side of the posterior
      compartment was more often affected (73.1% of cases) than the right side in all
      patients. CONCLUSION: In all, 69.23% of the cases (95% CI, 48.21-85.67%) were not
      explained by the classic risk factors. In view of the absence of other diseases
      and otherwise unremarkable parameters, we consider mechanical damage of the
      lesser pelvis not to be solely responsible for AMS. Further observations in
      patients with AMS, with and without endometriosis, may be able to contribute to
      research into the actual etiology of the condition.

PMID- 23855675
TI  - Validation of patient and nurse short forms of the Readiness for Hospital
      Discharge Scale and their relationship to return to the hospital.
AB  - OBJECTIVE: To validate patient and nurse short forms for discharge readiness
      assessment and their associations with 30-day readmissions and emergency
      department (ED) visits. DATA SOURCES/STUDY SETTING: A total of 254 adult medical
      surgical patients and their discharging nurses from an Eastern US tertiary
      hospital between May and November, 2011. STUDY DESIGN: Prospective longitudinal
      design, multinomial logistic regression analysis. DATA COLLECTION/EXTRACTION
      METHODS: Nurses and patients independently completed an eight-item Readiness for
      Hospital Discharge Scale on the day of discharge. Patient characteristics,
      readmissions, and ED visits were electronically abstracted. PRINCIPAL FINDINGS:
      Nurse assessment of low discharge readiness was associated with a six- to nine
      fold increase in readmission risk. Patient self-assessment was not associated
      with readmission; neither was associated with ED visits. CONCLUSIONS: Nurse
      discharge readiness assessment should be added to existing strategies for
      identifying readmission risk.

PMID- 23855676
TI  - Influence of objective three-dimensional measures and movement images on surgeon
      treatment planning for lip revision surgery.
AB  - Objective : To determine whether a systematic evaluation of facial soft tissues
      of patients with cleft lip and palate, using facial video images and objective
      three-dimensional measurements of movement, change surgeons' treatment plans for
      lip revision surgery. Design : Prospective longitudinal study. Setting : The
      University of North Carolina School of Dentistry. Patients, Participants : A
      group of patients with repaired cleft lip and palate (n = 21), a noncleft control
      group (n = 37), and surgeons experienced in cleft care. Interventions : Lip
      revision. Main Outcome Measures : (1) facial photographic images; (2) facial
      video images during animations; (3) objective three-dimensional measurements of
      upper lip movement based on z scores; and (4) objective dynamic and visual three
      dimensional measurement of facial soft tissue movement. Results : With the use of
      the video images plus objective three-dimensional measures, the operating surgeon
      changed the problem list of the surgical treatment plan for 86% of the patients
      (95% confidence interval, 0.64 to 0.97) and the surgical goals for 71% of the
      patients (95% confidence interval, 0.48 to 0.89). The surgeon group varied in the
      percentage of patients for whom the problem list was modified, ranging from 24%
      (95% confidence interval, 8% to 47%) to 48% (95% confidence interval, 26% to 70%)
      of patients, and the percentage for whom the surgical goals were modified,
      ranging from 14% (94% confidence interval, 3% to 36%) to 48% (95% confidence
      interval, 26% to 70%) of patients. Conclusions : For all surgeons, the additional
      assessment components of the systematic valuation resulted in a change in
      clinical decision making for some patients. 

PMID- 23855677
TI  - Comparison of invasive versus noninvasive blood pressure measurements before and
      after hemorrhage in anesthetized greyhounds using the Surgivet V9203.
AB  - OBJECTIVE: To determine the agreement between blood pressure obtained with a
      noninvasive technique and direct technique using the Surgivet V9203 at varying
      blood pressure levels created using a canine hemorrhage model. DESIGN:
      Experimental study. SETTING: University Teaching Hospital. ANIMALS: Twenty-nine
      greyhounds with an average weight of 30 kg. Approval from the Murdoch University
      Animal Ethics Committee was obtained (R228609). METHODS: Arterial blood pressure
      (BP) was measured noninvasively (NIBP) via a cuff placed over the dorsal
      metatarsal artery and via a catheter in the contralateral dorsal metatarsal
      artery (IBP). Retrospectively the blood pressure measurements recorded were
      divided into various BP categories. A total of 84 paired readings were obtained.
      The data were further analyzed with respect to heart rate [<120/min and
      >120/min]. Comparison of the measurements was performed using the Bland-Altman
      method. RESULTS: For all categories, BP measurements were generally lower when
      recorded using the oscillometric technique [Systolic (Sys) bias 4.20 kPa (31.54
      mm Hg), mean bias 0.52 kPa (3.93 mm Hg), and diastolic bias 1.04 kPa (7.83 mm
      Hg)]. Mean arterial BP had the least bias and greatest precision in the
      hypotensive group (bias 0.174 kPa (1.3063 mm Hg), precision 0.79 kPa (5.89 mm
      Hg)), low BP group (bias 0.62 kPa (4.67mm Hg) and precision 0.89 kPa (6.67mm Hg))
      and normotensive group [bias 0.76 kPa (5.71 mm Hg) and precision 1.16 kPa (8.73
      mmHg)]. CONCLUSIONS: The results demonstrate that the agreement between NIBP
      measurements and IBP, are within the limits of agreement recommended by the
      American College of Veterinary Internal Medicine Hypertension Consensus Panel for
      all pressures except Sys BP. This suggests that mean and diastolic NIBP using the
      Surgivet V9203 are a clinically acceptable alternative of IBP in hypovolemic
      hypotensive dogs.

PMID- 23855678
TI  - Efficient synthesis of imino-methano Troger bases by nitrene insertions into C-N
      bonds.
AB  - A direct nitrene insertion into C-N bonds is observed upon treatment of methano
      Troger bases with arylsulfonyl iminophenyliodinanes under copper and dirhodium
      catalysis. Novel cyclic imino-methano Troger bases are obtained (55-88%).
      Enantiopure products (ee >= 99%) can be obtained with tailored substrates. 

PMID- 23855679
TI  - Antioxidant and antidiabetic profiles of two African medicinal plants: Picralima
      nitida (Apocynaceae) and Sonchus oleraceus (Asteraceae).
AB  - BACKGROUND: Diabetes mellitus (DM) is a metabolic disease characterized by
      chronic hyperglycaemia generally associated with oxidative stress. The present
      study aims at evaluating the antioxidant and antidiabetic potential of methanol
      and hydroethanol extracts of the stem bark and leaves of Pricralima nitida and
      the Sonchus oleraceus whole plant respectively. METHODS: The in vitro antioxidant
      activity was assessed using 1,1-Diphenyl-2-picrilhydrazyl (DPPH) for free radical
      scavenging properties of the extracts, and the Folin-Ciocalteu method in
      determining their phenol contents. The antidiabetic activity was tested in mice
      following streptozotocin diabetes induction, and selected oxidative stress
      markers (Malondialdehyde, Hydrogen peroxides and Catalase) were measured in order
      to evaluate the level of oxidative stress in treated animals. RESULTS: The in
      vitro antioxidant activity using DPPH showed IC50 ranging from 0.19 +/- 0.08 to
      1.00 +/- 0.06 mg/mL. The highest activity was obtained with the hydroethanol
      extracts of S. oleraceus (0.19 mg/mL and P. nitida (0.24 mg/mL). Polyphenol
      contents ranged from 182.25 +/- 16.76 to 684.62 +/- 46.66 MUg Eq Cat/g. The
      methanol extract of P. nitida showed the highest activity, followed by the
      hydroethanol extract of S. oleraceus (616.89 +/- 19.20 MUEq Cat/g). The
      hydroethanol extract of whole plants (150 mg/Kg) and methanol leave extract of P.
      nitida (300 mg/Kg) exhibited significant antidiabetic activities with 39.40% and
      38.48% glycaemia reduction, respectively. The measurement of stress markers in
      plasma, liver and kidney after administration of both extracts showed significant
      reduction in MDA and hydrogen peroxide levels, coupled with a substantial
      increase in catalase activity. CONCLUSIONS: These findings suggest that S.
      oleraceus whole plant and P. nitida leaves possess both antidiabetic and
      antioxidant properties, and therefore could be used as starting point for the
      development of herbal medicines and/or source of new drug molecules against
      diabetes.

PMID- 23855680
TI  - In vitro analysis of equine, bone marrow-derived mesenchymal stem cells
      demonstrates differences within age- and gender-matched horses.
AB  - REASONS FOR PERFORMING THE STUDY: Stem cell therapies are used routinely in
      equine practice. Most published reports characterise stem cells derived from
      younger horses; however, middle-aged horses are often in athletic performance,
      and experience degenerative medical conditions. Thus, mesenchymal stem cells
      (MSCs) from this group should be investigated. OBJECTIVE: To describe differences
      in in vitro adherence, proliferation and potential for differentiation of equine
      bone marrow-derived MSCs (equine BMMSCs) harvested from middle-aged (10-13 years
      old) female donors. STUDY DESIGN: Descriptive study of stem cell characteristics.
      METHODS: Equine BMMSCs from 6 horses were cultured in vitro and evaluated for
      viability, proliferation, osteogenesis, chondrogenesis, adipogenesis, cluster-of
      differentiation markers and gene expression. RESULTS: Equine BMMSCs from all 6
      donors demonstrated fibroblastic, cellular morphology, adherence to plastic and
      expression of cluster-of-differentiation markers. They varied in their rate of
      proliferation and trilineage differentiation. The equine BMMSCs of one of 6
      donors demonstrated a higher rate of proliferation, enhanced ability for cell
      passaging and a more robust in vitro differentiation. Comparatively, equine
      BMMSCs from 2 donors demonstrated a lower rate of proliferation and lack of
      osteogenic and chondrogenic differentiation. CONCLUSION: The results of this
      study confirm that donor-to-donor variation in equine BMMSCs exists and this
      variation can be documented using in vitro assays. Subjective assessment suggests
      that the rate of proliferation tends to correlate with differentiation potential.

PMID- 23855681
TI  - Investigating chromosome damage using fluorescent in situ hybridization to
      identify biomarkers of radiosensitivity in prostate cancer patients.
AB  - PURPOSE: In order to evaluate fluorescent in situ hybridization (FISH) as a
      method for predicting radiosensitivity, this study examined the incidence of
      translocations, after exposure to in vitro radiation, in both normally responding
      patients and those exhibiting severe late effects after radiotherapy treatment.
      MATERIALS AND METHODS: Patients were selected from a randomized trial for
      intermediate-risk prostate cancer. Of the patients entered on trial with mature
      follow-up, 3% developed grade 3 late proctitis. Blood samples were taken from
      this radiosensitive cohort along with matched control patients with no late
      proctitis. Whole blood samples were exposed to 0 or 4 Gy and cultured according
      to the International Atomic Energy Agency (IAEA) recommended methods. Colour
      junctions were evaluated in the resulting metaphases and scored according to the
      Protocol for Aberration Identification and Nomenclature Terminology (PAINT)
      system. RESULTS: Both groups were statistically similar at 0 Gy. After 4 Gy in
      vitro radiation, the radiosensitive group had significantly higher rates of
      chromosome damage in the number of colour junctions per cell (p = 0.002), the
      number of deletions per cell (p = 0.01) and the number of dicentrics per cell (p
      = 0.005). CONCLUSIONS: These results indicate that the analysis of translocations
      using FISH after in vitro irradiation correlates with clinical response to
      radiation. This cytogenetic assay should be considered as a potential predictor
      of radiosensitivity.

PMID- 23855682
TI  - Limitations of radiology in rickets.

PMID- 23855683
TI  - Effectiveness of an electronic inpatient medication record in reducing medication
      errors in Singapore.
AB  - This study examined the effectiveness of an inpatient electronic medication
      record system in reducing medication errors in Singaporean hospitals. This pre-
      and post-intervention study involving a control group was undertaken in two
      Singaporean acute care hospitals. In one hospital the inpatient electronic
      medication record system was implemented while in another hospital the paper
      based medication record system was used. The mean incidence difference in
      medication errors of 0.06 between pre-intervention (0.72 per 1000 patient days)
      and post-intervention (0.78 per 1000 patient days) for the two hospitals was not
      statistically significant (95%, CI: [0.26, 0.20]). The mean incidence differences
      in medication errors relating to prescription, dispensing, and administration
      were also not statistically different. Common system failures involved a lack of
      medication knowledge by health professionals and a lack of a systematic approach
      in identifying correct dosages. There was no difference in the incidence of
      medication errors following the introduction of the electronic medication record
      system. More work is needed on how this system can reduce medication error rates
      and improve medication safety.

PMID- 23855684
TI  - Cushing syndrome and rebound generalized pustular psoriasis from Chinese herbs.

PMID- 23855685
TI  - Management of chronic osteomyelitis of the tibia with life-threatening
      complications under negative pressure wound therapy and isolation of Helcococcus
      kunzii.
AB  - We report the case of an 86-year-old man with severe wound infection originating
      from a chronic crural ulcer of the lower limb, which under negative pressure
      wound therapy led to excessive tissue necrosis and perforation of the anterior
      tibial artery. A swab taken 10 and 7 days preoperatively was positive for
      Helcococcus kunzii. H. kunzii has been described as a potentially pathogenic
      organism. The questions whether the negative pressure wound therapy itself caused
      the bleeding or the negative pressure wound therapy, which generates an anaerobic
      atmosphere, has triggered the growth and invasion of the facultative anaerobic
      bacterium H. kunzii and owing to the infection the artery perforated or whether
      the bacteria has no influence at all remain currently unanswered. After surgical
      debridement the signs of infection were completely eliminated, and a free
      musculocutaneous flap led to rapid healing of the wound. Following which H.
      kunzii was no longer detectable. 

PMID- 23855686
TI  - Cell therapy trials for lung diseases: progress and cautions.

PMID- 23855687
TI  - Triggering receptor expressed on myeloid cells-2: a new ally against sepsis.

PMID- 23855688
TI  - Has the twitching hour arrived for the ventilated patient?

PMID- 23855689
TI  - Mechanical ventilation, clinical trials, and glaciers.

PMID- 23855690
TI  - The seventh patient.

PMID- 23855691
TI  - Update in asthma 2012.

PMID- 23855694
TI  - Fatal air embolism. A rare complication of bronchogenic cysts in an airplane
      passenger.

PMID- 23855693
TI  - Markers of vascular perturbation correlate with airway structural change in
      asthma.
AB  - RATIONALE: Air trapping and ventilation defects on imaging are characteristics of
      asthma. Airway wall thickening occurs in asthma and is associated with increased
      bronchial vascularity and vascular permeability. Vascular endothelial cell
      products have not been explored as a surrogate to mark structural airway changes
      in asthma. OBJECTIVES: Determine whether reporters of vascular endothelial cell
      perturbation correlate with airway imaging metrics in patients with asthma of
      varying severity. METHODS: Plasma from Severe Asthma Research Program subjects
      was analyzed by ELISAs for soluble von Willebrand factor mature protein (VWF:Ag)
      and propeptide (VWFpp), P-selectin, and platelet factor 4. Additional subjects
      were analyzed over 48 hours after whole-lung antigen challenge. We calculated
      ventilation defect volume by hyperpolarized helium-3 magnetic resonance imaging
      and areas of low signal density by multidetector computed tomography (less than 
      856 Hounsfield units [HU] at functional residual capacity and -950 HU at total
      lung capacity [TLC]). MEASUREMENTS AND MAIN RESULTS: VWFpp and VWFpp/Ag ratio
      correlated with and predicted greater percentage defect volume on hyperpolarized
      helium-3 magnetic resonance imaging. P-selectin correlated with and predicted
      greater area of low density on chest multidetector computed tomography less than 
      950 HU at TLC. Platelet factor 4 did not correlate. Following whole-lung antigen
      challenge, variation in VWFpp, VWFpp/Ag, and P-selectin among time-points was
      less than that among subjects, indicating stability and repeatability of the
      measurements. CONCLUSIONS: Plasma VWFpp and P-selectin may be useful as
      surrogates of functional and structural defects that are evident on imaging. The
      results raise important questions about why VWFpp and P-selectin are associated
      specifically with different imaging abnormalities.

PMID- 23855695
TI  - Steep barriers to overcome for successful application of stem cell treatment in
      patients with idiopathic pulmonary fibrosis.

PMID- 23855692
TI  - Update in lung cancer and mesothelioma 2012.

PMID- 23855696
TI  - Idiopathic pulmonary fibrosis: a degenerative disease requiring a regenerative
      approach.

PMID- 23855697
TI  - Reply: idiopathic pulmonary fibrosis: a degenerative disease requiring a
      regenerative approach.

PMID- 23855698
TI  - Assessment of endobronchial ultrasound-guided transbronchial needle aspiration
      performance.

PMID- 23855699
TI  - The impact of the introduction of an endobronchial ultrasound-guided
      transbronchial needle aspiration program on teaching of conventional
      bronchoscopic sampling techniques in an academic institution.

PMID- 23855700
TI  - Reply: the impact of the introduction of an endobronchial ultrasound
      transbronchial needle aspiration program on teaching of conventional
      bronchoscopic sampling techniques in an academic institution.

PMID- 23855701
TI  - Reply: Endobronchial Ultrasound Skills and Tasks Assessment Tool (EBUS-STAT).

PMID- 23855702
TI  - Enhanced innate immunity as explanation for reduced Mycobacterium tuberculosis
      infection in Bacillus Calmette-Guerin-immunized children.

PMID- 23855703
TI  - The road to personalized and predictive medicine.

PMID- 23855704
TI  - Assessment of a pulmonary origin for blood outgrowth endothelial cells by
      examination of identical twins harboring a BMPR2 mutation.

PMID- 23855705
TI  - Twitch transdiaphragmatic pressure morphology can distinguish diaphragm paralysis
      from a diaphragm defect.

PMID- 23855706
TI  - Case of sunitinib-induced Stevens-Johnson syndrome.

PMID- 23855707
TI  - Nonconvective mixing of miscible ionic liquids.
AB  - Ionic liquids (ILs) are ionic compounds that are liquid at room temperature. We
      studied the spontaneous mixing behavior between two ILs, ethylammonium nitrate
      (EAN) and 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]), and
      observed notable phenomena. Experimental studies showed that the interface
      between the two ILs was unusually long-lived, despite the ILs being miscible with
      one another. Molecular dynamics (MD) simulations supported these findings and
      provided insight into the micromixing behavior of the ILs. We found that not only
      did the ions experience slow diffusion as they mix but also exhibited significant
      ordering into distinct regions. We suspect that this ordering disrupted
      concentration gradients in the direction normal to the interface, thus hindering
      diffusion in this direction and allowing the macroscopic interface to remain for
      long periods of time. Intermolecular interactions responsible for this behavior
      included the O-NH interaction between the EAN ions and the carbon chain-carbon
      chain interactions between the [BMIM](+) cations, which associate more strongly
      in the mixed state than in the pure IL state. 

PMID- 23855709
TI  - Quantification of bone changes in a collagen-induced arthritis mouse model by
      reconstructed three dimensional micro-CT.
AB  - BACKGROUND: Inflammatory arthritis is a chronic disease, resulting in synovitis
      and subchondral and bone area destruction, which can severely affect a patient's
      quality of life. The most common form of inflammatory arthritis is rheumatoid
      arthritis (RA) in which many of the disease mechanisms are not well understood.
      The collagen-induced arthritis (CIA) mouse model is similar to RA as it exhibits
      joint space narrowing and bone erosion as well as involves inflammatory factors
      and cellular players that have been implicated in RA pathogenesis. Quantitative
      data for disease progression in RA models is difficult to obtain as serum blood
      markers may not always reflect disease state and physical disease indexes are
      subjective. Thus, it is important to develop tools to objectively assess disease
      progression in CIA. RESULTS: Micro-CT (Computed Tomography) is a relatively
      mature technology that has been used to track a variety of anatomical changes in
      small animals. In this study, micro-CT scans of several joints of control and CIA
      mice were acquired at 0, 4, 7, and 9 weeks after the immunization with collagen
      type II. Each micro-CT scan was analyzed by applying a segmentation algorithm to
      individual slices in each image set to provide 3-dimensional representations of
      specific bones including the humerus, femur, and tibia. From these
      representations, the volume and mean density of these bones were measured and
      compared. This analysis showed that both the volume and the density of each
      measured bone of the CIA mice were significantly smaller than those of the
      controls at week 7. CONCLUSIONS: This study demonstrates that micro-CT can be
      used to quantify bone changes in the CIA mouse model as an alternative to disease
      index assessments. In conclusion, micro-CT could be useful as a non-invasive
      method to monitor the efficacy of new treatments for RA tested in small animals.

PMID- 23855708
TI  - Developing a complex intervention for diet and activity behaviour change in obese
      pregnant women (the UPBEAT trial); assessment of behavioural change and process
      evaluation in a pilot randomised controlled trial.
AB  - BACKGROUND: Complex interventions in obese pregnant women should be theoretically
      based, feasible and shown to demonstrate anticipated behavioural change prior to
      inception of large randomised controlled trials (RCTs). The aim was to determine
      if a) a complex intervention in obese pregnant women leads to anticipated changes
      in diet and physical activity behaviours, and b) to refine the intervention
      protocol through process evaluation of intervention fidelity. METHODS: We
      undertook a pilot RCT of a complex intervention in obese pregnant women,
      comparing routine antenatal care with an intervention to reduce dietary glycaemic
      load and saturated fat intake, and increase physical activity. Subjects included
      183 obese pregnant women (mean BMI 36.3 kg/m2). RESULTS: Compared to women in the
      control arm, women in the intervention arm had a significant reduction in dietary
      glycaemic load (33 points, 95% CI -47 to -20), (p < 0.001) and saturated fat
      intake (-1.6% energy, 95% CI -2.8 to -0. 3) at 28 weeks' gestation. Objectively
      measured physical activity did not change. Physical discomfort and sustained
      barriers to physical activity were common at 28 weeks' gestation. Process
      evaluation identified barriers to recruitment, group attendance and compliance,
      leading to modification of intervention delivery. CONCLUSIONS: This pilot trial
      of a complex intervention in obese pregnant women suggests greater potential for
      change in dietary intake than for change in physical activity, and through
      process evaluation illustrates the considerable advantage of performing an
      exploratory trial of a complex intervention in obese pregnant women before
      undertaking a large RCT. TRIAL REGISTRATION:  TRIAL REGISTRATION NUMBER:
      ISRCTN89971375.

PMID- 23855710
TI  - The carbonylation and covalent dimerization of human superoxide dismutase 1
      caused by its bicarbonate-dependent peroxidase activity is inhibited by the
      radical scavenger tempol.
AB  - Tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) reduces tissue injury in
      animal models of various diseases via mechanisms that are not completely
      understood. Recently, we reported that high doses of tempol moderately increased
      survival in a rat model of ALS (amyotrophic lateral sclerosis) while decreasing
      the levels of oxidized hSOD1 (human Cu,Zn-superoxide dismutase) in spinal cord
      tissues. To better understand such a protective effect in vivo, we studied the
      effects of tempol on hSOD1 oxidation in vitro. The chosen oxidizing system was
      the bicarbonate-dependent peroxidase activity of hSOD1 that consumes H2O2 to
      produce carbonate radical, which oxidizes the enzyme. Most of the experiments
      were performed with 30 MUM hSOD1, 25 mM bicarbonate, 1 mM H2O2, 0.1 mM DTPA
      (diethylenetriaminepenta-acetic acid) and 50 mM phosphate buffer at a final pH of
      7.4. The results showed that tempol (5-75 MUM) does not inhibit hSOD1 turnover,
      but decreases its resulting oxidation to carbonylated and covalently dimerized
      forms. Tempol acted by scavenging the carbonate radical produced and by
      recombining with hSOD1-derived radicals. As a result, tempol was consumed nearly
      stoichiometrically with hSOD1 monomers. MS analyses of turned-over hSOD1 and of a
      related peptide oxidized by the carbonate radical indicated the formation of a
      relatively unstable adduct between tempol and hSOD1-Trp32*. Tempol consumption by
      the bicarbonate-dependent peroxidase activity of hSOD1 may be one of the reasons
      why high doses of tempol were required to afford protection in an ALS rat model.
      Overall, the results of the present study confirm that tempol can protect against
      protein oxidation and the ensuing consequences. 

PMID- 23855711
TI  - Impact of early diagnosis and control of chronic respiratory diseases on active
      and healthy ageing. A debate at the European Union Parliament.
AB  - A debate at the European Union Parliament was held on 13 November 2012 on the
      Impact of early diagnosis and control of chronic respiratory diseases on Active
      and Healthy Ageing (AHA). The debate was held under the auspices of the Cyprus
      Presidency of the European Union (2012) and represents a follow-up of the
      priorities of the Polish Presidency of the European Union (2011). It highlighted
      the importance of early life events on the occurrence of chronic respiratory
      diseases later in life and their impact on active and healthy ageing.
      Epidemiologic evidence was followed by actions that should be taken to prevent
      and manage chronic respiratory diseases in children. The debate ended by
      practical, feasible and achievable projects, demonstrating the strength of the
      political action in the field. Three projects will be initiated from this debate:
      The first will be a meeting sponsored by the Region Languedoc-Roussillon on the
      developmental origins of chronic diseases and ageing: from research to policies
      and value creation. The second project is being led by the WHO Collaborating
      Centre for Asthma and Rhinitis: Prevention of Asthma, Prevention of Allergy
      (PAPA). The third project is the GA(2)LEN sentinel network.

PMID- 23855712
TI  - An experimental study of the solvent-dependent self-assembly/disassembly and
      conformer preferences of gramicidin A.
AB  - The solvent dependence of self-assembly/disassembly kinetics and conformer
      preferences of the gramicidin A (GA) dimer is investigated using a combination of
      techniques, viz., electrospray ionization-ion mobility-mass spectrometry (IM-MS),
      collision-induced dissociation (CID), and hydrogen/deuterium exchange (HDX)-MS.
      IM-MS measurements reveal that there are possibly three distinct GA dimeric
      species, detected as sodium ion adduct ions [2GA + 2Na](2+), and these are
      assigned as the parallel beta-helix, antiparallel beta-helix, and head-to-head
      dimer. The monomerization kinetics and equilibrium abundances of the dimer ions
      depend upon solvent polarity. The antiparallel beta-helix was the
      thermodynamically preferred species in less polar solvents. HDX measurements and
      collision-induced dissociation (CID) of the intermediate complex confirm the well
      protected dimer geometry with strong intermolecular hydrogen bonds. This combined
      IM-HDX-CID methodology provides a comprehensive view of GA self
      assembly/disassembly in low dielectric solutions, showing its potential utility
      in solving solution-phase protein self-assembly/disassembly kinetics and
      providing structural information of the multimers at the same time. 

PMID- 23855713
TI  - Reduction of carcinogenic polycyclic aromatic hydrocarbons in meat by sugar
      smoking and dietary exposure assessment in taiwan.
AB  - Polycyclic aromatic hydrocarbons (PAHs) represent an important pollutant in foods
      and/or the environment. This study aimed to determine the PAH contents in sugar
      smoked meat by employing a quick, easy, cheap, effective, rugged, safe (QuEChERS)
      method combined with a GC-MS technique and assess the dietary exposure of PAHs in
      Taiwan. Results showed that the longer the sugar-smoking duration, the more the
      total PAH formation. By sugar-smoking for 6 min, the total PAH contents generated
      in red meat (33.9 +/- 3.1-125.5 +/- 9.2 ppb) were higher than in poultry meat
      (19.1 +/- 2.0-28.2 +/- 1.2 ppb) and seafood (9.1 +/- 1.4-31.8 +/- 1.8 ppb), with
      lamb steak containing the largest amount of total PAHs. Most importantly, the
      highly carcinogenic benzo[a]pyrene remained undetected in all of the sugar-smoked
      meat samples. In addition, the cancer risk due to dietary PAH exposure based on
      total intake of meat in Taiwan was <2 * 10(-7). This outcome demonstrates that
      sugar-smoking can be adopted to replace the traditional smoking process with wood
      as smoke source. 

PMID- 23855714
TI  - SLiMScape: a protein short linear motif analysis plugin for Cytoscape.
AB  - BACKGROUND: Computational protein short linear motif discovery can use protein
      interaction information to search for motifs among proteins which share a common
      interactor. Cytoscape provides a visual interface for protein networks but there
      is no streamlined way to rapidly visualize motifs in a network of proteins, or to
      integrate computational discovery with such visualizations. RESULTS: We present
      SLiMScape, a Cytoscape plugin, which enables both de novo motif discovery and
      searches for instances of known motifs. Data is presented using Cytoscape's
      visualization features thus providing an intuitive interface for interpreting
      results. The distribution of discovered or user-defined motifs may be selectively
      displayed and the distribution of protein domains may be viewed simultaneously.
      To facilitate this SLiMScape automatically retrieves domains for each protein.
      CONCLUSION: SLiMScape provides a platform for performing short linear motif
      analyses of protein interaction networks by integrating motif discovery and
      search tools in a network visualization environment. This significantly aids in
      the discovery of novel short linear motifs and in visualizing the distribution of
      known motifs.

PMID- 23855715
TI  - Parathion hydrolysis revisited: in situ aqueous kinetics by (1)h NMR.
AB  - The kinetics of parathion (PTH) decomposition into para-nitrophenolate (pNP) and
      O,O-diethylthiophosphate (DETP) were measured in high-pH aqueous solutions at 20 
      degrees C by proton nuclear magnetic resonance spectroscopy ((1)H NMR). Reaction
      rates were determined over a 16 h observation time, in solutions with NaOD
      concentrations of 5.33 mM, 33.33 mM, and 100 mM, with NaCl added to fix ionicity.
      The pseudo-first-order rate constants for these systems were determined to be 1.9
      * 10(-4) min(-1), 1.4 * 10(-3) min(-1), and 3.8 * 10(-3) min(-1) respectively.
      The slope of the linear plot of these rates against OD(-) concentration yielded
      the second-order hydrolysis rate constant 3.90 * 10(-5) mM(-1) min(-1), valid
      over this pH range from 10.5 to 13. The data agree with some, and contradict
      other, earlier work. Our fitting procedure included background levels and allowed
      us to not only obtain reliable kinetic results but also to measure residual pNP
      and DETP impurity levels. 

PMID- 23855716
TI  - Polymorphisms in CYP2D6 may predict methamphetamine related heart failure.
AB  - BACKGROUND: Methamphetamine (METH) has been associated with a dilated
      cardiomyopathy. The first and rate-limiting step of metabolism is dependent on
      the polymorphic enzyme CYP2D6. OBJECTIVES: To evaluate if polymorphisms in CYP2D6
      can be associated with the development of a methamphetamine-induced
      cardiomyopathy. METHODS: We performed a prospective case-control pilot study.
      Cases were defined by a urinary drug screen positive for amphetamine and evidence
      of heart failure by beta natriuretic peptide (BNP) greater than 300 pg/ml and
      symptoms of heart failure. Controls were defined with urinary drug screens
      positive for amphetamines but without evidence of heart failure defined by a BNP
      lesser than 300 pg/ml or symptoms of heart failure. Exclusion criteria were less
      than 18 years or greater than 60 years of age, urinary toxicology screen positive
      for additional stimulants, known coronary artery disease (CAD) defined by greater
      than 50% stenosis on catheterization or previous myocardial infarction, known
      cardiomyopathy of alternative etiology or inability to provide consent. Patients
      underwent gas chromatography confirmation-mass spectroscopy for methamphetamine,
      genotyping of CYP2D6, limited echocardiography, and participated in a modified
      2007 National Survey of Drug Use and Health Stimulant Survey. Genotype results
      were analyzed with traditional classifications and "Activity Scores". RESULTS:
      Fifty-six patients completed the study with 19 cases and 37 controls. There was
      no statistically significant difference in days of use in a month, age, gender,
      or ethnicity between cases and controls. While not statistically significant, age
      and days of use did trend higher in cases. CYP2D6 genotype demonstrated that the
      lower the activity score/poor metabolizer group had less heart failure than
      extensive metabolizers/higher activity score. However, it did not reach
      statistical significance. When adjusting for higher days of use, extensive
      metabolizers had the highest odds of developing a dilated cardiomyopathy. (OR:
      2.33, 95% CI: 0.54-10.13). Echo findings in all cases showed reduced ejection
      fractions with a mean of 18.6% (range: 10-35%) and 70% had a dilated
      cardiomyopathy. No cardiomyopathies were seen in the controls. Mean ejection
      fraction was 56.75% (range: 45-70%). The odds ratio of having a dilated
      cardiomyopathy in extensive metabolizers was 1.62 (95% CI: 0.47-5.5). CONCLUSION:
      Our study demonstrates a trend that individuals with decreased metabolic activity
      were less likely to develop heart failure. While not statistically significant, a
      signal is present that extensive metabolizers may be at increased risk for the
      development of a cardiomyopathy.

PMID- 23855717
TI  - Perinatal outcomes of low-risk planned home and hospital births under midwife-led
      care in Japan.
AB  - AIM: It has not been extensively studied whether planned home and planned
      hospital births under primary midwife-led care increase risk of adverse events
      among low-risk women in Japan. METHODS: A retrospective cohort study was
      performed to compare perinatal outcome between 291 women who were given primary
      midwife-led care during labor and 217 women who were given standard obstetric
      shared care. Among 291 women with primary midwife-led care, 168 and 123 chose
      home deliver and hospital delivery, respectively. Perinatal outcomes included
      length of labor of 24 h or more, augmentation of labor pains, delivery mode,
      severe perineal laceration, postpartum hemorrhage of 1000 mL or more, maternal
      fever of 38 degrees C or more and neonatal asphyxia (Apgar score, <7). Analysis
      was by intention to treat. RESULTS: The incidence of transfer from primary
      midwife-led care to obstetric shared care was 27% (77 women) mainly due to
      failure of labor progress (21%, 16 women), postpartum hemorrhage (19%, 15 women)
      and non-reassuring fetal status (19%, 15 women). Significantly higher incidence
      of transfer to obstetric shared care from primary midwife-led care was seen among
      women who chose hospital delivery compared with women who chose home delivery (34
      vs 21%, P = 0.011). There were no significant differences in the incidence of
      adverse perinatal outcomes between women with obstetric shared care and women
      with primary midwife-led care (regardless of being hospital delivery or home
      delivery). CONCLUSION: Approximately one-quarter of low-risk women with primary
      midwife-led care required obstetric care during labor or postpartum. However,
      primary midwife-led care during labor at home and hospital for low-risk pregnant
      women was not associated with adverse perinatal outcomes in Japan.

PMID- 23855718
TI  - Swallowing frequency in elderly people during daily life.
AB  - Disuse atrophy of swallowing-related organs due to an excessive decrease in
      swallowing frequency is suspected to occur in patients with poor oral intake,
      especially elderly people. However, swallowing frequency in daily life has not
      previously been examined in the elderly. This study examined swallowing frequency
      in elderly people and compared these findings to those in a younger population
      and differences in the degree of activity in daily life. (i) We compared
      swallowing frequency in 20 elderly people (82.0 +/- 8.3 year) and 15 healthy
      young people (26.5 +/- 3.5 year). (ii) 20 elderly people were divided into two
      groups according to the degree of activity in daily life: a semi-bedridden group
      and bedridden group; the swallowing frequency was compared between these groups.
      (i) The swallowing frequency in the elderly people was 2-19 times per hour and
      the mean was 9.4 +/- 4.9, and that in the healthy young people was 16-76 times
      per hour and the mean was 40.7 +/- 19.5. Swallowing frequency in elderly people
      was significantly lower than that in young healthy people (P < 0.0001). (ii) The
      swallowing frequency in bedridden group was 2-11 times per hour and the mean was
      6.8 +/- 3.3, and that in semi-bedridden group was 3-19 times per hour and the
      mean was 11.9 +/- 5.1. Swallowing frequency in bedridden group was significantly
      lower than that in semi-bedridden group (P < 0.05). These results indicate that
      in daily life, elderly people tend to swallow less frequently than young people.
      In addition, swallowing frequency was lower in elderly subjects with a low degree
      of activity in daily life.

PMID- 23855720
TI  - Microwave-assisted synthesis of high-voltage nanostructured LiMn1.5Ni0.5O4
      spinel: tuning the Mn3+ content and electrochemical performance.
AB  - The LiMn1.5Ni0.5O4 spinel is an important lithium ion battery cathode material
      that has continued to receive major research attention because of its high
      operating voltage (~4.8 V). This study interrogates the impact of microwave
      irradiation on the Mn(3+) concentration and electrochemistry of the
      LiMn1.5Ni0.5O4 spinel. It is shown that microwave is capable of tuning the Mn(3+)
      content of the spinel for enhanced electrochemical performance (high capacity,
      high capacity retention, excellent rate capability, and fast Li(+)
      insertion/extraction kinetics). This finding promises to revolutionize the
      application of microwave irradiation for improved performance of the
      LiMn1.5Ni0.5O4 spinel, especially in high rate applications. 

PMID- 23855719
TI  - Adoption and diffusion of evidence-based addiction medications in substance abuse
      treatment.
AB  - OBJECTIVE: To examine the roles of facility- and state-level factors in treatment
      facilities' adoption and diffusion of pharmaceutical agents used in addiction
      treatment. DATA SOURCES: Secondary data from the National Survey of Substance
      Abuse Treatment Services (N-SSATS), Substance Abuse and Mental Health Services
      Administration (SAMHSA), Centers for Medicare and Medicaid Services, Alcohol
      Policy Information System, and Kaiser Family Foundation. STUDY DESIGN: We
      estimate ordered logit and multinomial logit models to examine the relationship
      of state and treatment facility characteristics to the adoption and diffusion of
      three pharmaceutical agents over 4 years when each was at a different stage of
      adoption or diffusion. DATA COLLECTION: N-SSATS data with facility codes,
      obtained directly from SAMHSA, were linked by state identifiers to the other
      publicly available, secondary data. PRINCIPAL FINDINGS: The analysis confirms the
      importance of awareness and exposure to the adoption behavior of others,
      dissemination of information about the feasibility and effectiveness of
      innovations, geographical clustering, and licensing and accreditation in
      legitimizing facilities' adoption and continued use of pharmacotherapies in
      addiction treatment. CONCLUSIONS: Policy and administrative levers exist to
      increase the availability of pharmaceutical technologies and their continued use
      by substance abuse treatment facilities.

PMID- 23855721
TI  - Localization of BRCA1 protein in breast cancer tissue and cell lines with
      mutations.
AB  - BACKGROUND: The breast and ovarian cancer susceptibility gene (BRCA1) encodes a
      tumor suppressor. The BRCA1 protein is found primarily in cell nuclei and plays
      an important role in the DNA damage response and transcriptional regulation.
      Deficiencies in DNA repair capabilities have been associated with higher
      histopathological grade and worse prognosis in breast cancer. METHODS: In order
      to investigate the subcellular distribution of BRCA1 in tumor tissue we randomly
      selected 22 breast carcinomas and tested BRCA1 protein localization in frozen and
      contiguous formalin-fixed, paraffin embedded (FFPE) tissue, using pressure cooker
      antigen-retrieval and the MS110 antibody staining. To assess the impact of BRCA1
      germline mutations on protein localization, we retrospectively tested 16 of the
      tumor specimens to determine whether they contained the common Ashkenazi Jewish
      founder mutations in BRCA1 (185delAG, 5382insC), and BRCA2 (6174delT). We also
      compared co-localization of BRCA1 and nucleolin in MCF7 cells (wild type) and a
      mutant BRCA1 cell line, HCC1937 (5382insC). RESULTS: In FFPE tissue, with MS110
      antibody staining, we frequently found reduced BRCA1 nuclear staining in breast
      tumor tissue compared to normal tissue, and less BRCA1 staining with higher
      histological grade in the tumors. However, in the frozen sections, BRCA1 antibody
      staining showed punctate, intra-nuclear granules in varying numbers of tumor,
      lactating, and normal cells. Two mutation carriers were identified and were
      confirmed by gene sequencing. We have also compared co-localization of BRCA1 and
      nucleolin in MCF7 cells (wild type) and a mutant BRCA1 cell line, HCC1937
      (5382insC) and found altered sub-nuclear and nucleolar localization patterns
      consistent with a functional impact of the mutation on protein localization.
      CONCLUSIONS: The data presented here support a role for BRCA1 in the pathogenesis
      of sporadic and inherited breast cancers. The use of well-characterized reagents
      may lead to further insights into the function of BRCA1 and possibly the further
      development of targeted therapeutics.

PMID- 23855722
TI  - Effect of chain architecture on the compression behavior of nanoscale
      polyethylene particles.
AB  - Polymeric particles with controlled internal molecular architectures play an
      important role as constituents in many composite materials for a number of
      emerging applications. In this study, classical molecular dynamics techniques are
      employed to predict the effect of chain architecture on the compression behavior
      of nanoscale polyethylene particles subjected to simulated flat-punch testing.
      Cross-linked, branched, and linear polyethylene chain architectures are each
      studied in the simulations. Results indicate that chain architecture has a
      significant influence on the mechanical properties of polyethylene nanoparticles,
      with the network configuration exhibiting higher compressive strengths than the
      branched and linear architectures. These findings are verified with simulations
      of bulk polyethylene. The compressive stress versus strain profiles of particles
      show four distinct regimes, differing with that of experimental micron-sized
      particles. The results of this study indicate that the mechanical response of
      polyethylene nanoparticles can be custom-tailored for specific applications by
      changing the molecular architecture. 

PMID- 23855723
TI  - Evaluation of the shock index in dogs presenting as emergencies.
AB  - OBJECTIVES: To (1) determine a reference interval for shock index (SI) [defined
      as heart rate (HR)/systolic blood pressure (SBP)], in a group of healthy dogs,
      and (2) compare SI in healthy dogs with dogs presenting to the emergency room
      (ER) deemed to be in or not in a state of shock. DESIGN: Prospective study.
      ANIMALS: Sixty-eight clinically normal dogs, 18 dogs that were presented to the
      ER deemed to be in shock and 19 dogs presenting to the ER not deemed to be in
      shock. SETTING: University teaching hospital. INTERVENTIONS: Peripheral or
      central venous blood sampling. MEASUREMENTS AND MAIN RESULTS: Heart rate and SBP
      were recorded on simulated presentation (healthy dogs), and emergency
      presentations for both dogs deemed to be in shock and dogs not deemed in shock.
      Dogs in shock had a median SI of 1.37 (0.87-3.13), which was significantly higher
      than both other groups; dogs not deemed in shock had median SI 0.73 (0.56-1.20),
      P < 0.0001 and healthy dogs had median SI 0.78 (0.37-1.30) P < 0.0001),
      respectively. Receiver operator characteristic curve analysis suggested a SI cut
      off of 1.0, yielding an area under the receiver operator characteristic (AUROC)
      of 0.89 (Specificity (Sp) 89, Sensitivity (Sn) 90) when comparing dogs deemed in
      shock with healthy dogs, and 0.92 (Sp 95, Sn 89) when comparing dogs in shock
      with to dogs not deemed in shock. CONCLUSIONS: The SI is an easy and noninvasive
      patient parameter that is higher in dogs that are deemed to be in shock than both
      healthy dogs and dogs presented as emergencies but not deemed to be in a state of
      shock. The measurement of SI may have some benefit in clinical assessment of
      emergency patients.

PMID- 23855724
TI  - HIV testing in the nation's opioid treatment programs, 2005-2011: the role of
      state regulations.
AB  - OBJECTIVE: To identify the extent to which clients in a national sample of opioid
      treatment programs (OTPs) received HIV testing in 2005 and 2011; to examine
      relationships between state laws for informed consent and pretest counseling and
      rates of HIV testing among OTP clients. DATA SOURCE: Data were collected from a
      nationally representative sample of OTPs in 2005 (n = 171) and 2011 (n = 200).
      STUDY DESIGN: Random-effects logit and interval regression analyses were used to
      examine changes in HIV testing rates and the relationship of state laws to HIV
      testing among OTPs. DATA COLLECTION: Data on OTP provision of HIV testing were
      collected in phone surveys from OTP managers; data also were collected on state
      laws for HIV testing. PRINCIPAL FINDINGS: The percentage of OTPs offering HIV
      testing decreased significantly from 93 percent in 2005 to 64 percent in 2011.
      Similarly, the percentage of clients tested decreased from an average of 41
      percent in 2005 to 17 percent in 2011. OTPs located in states whose laws do not
      require pretest counseling and that use opt-out consent were more likely to
      provide HIV testing and to test higher percentages of clients. CONCLUSIONS: The
      results show the need to increase HIV testing among OTP clients; the results also
      underscore the beneficial possibilities of dropping pretest counseling as a
      requirement for HIV testing and of using the opt-out approach to informed consent
      for testing.

PMID- 23855725
TI  - Physiological and performance responses to the "FIFA 11+" (part 1): is it an
      appropriate warm-up?
AB  - The aim of the study was to examine the post-exercise effects of the "FIFA 11+"
      on various physical performance and physiological variables, to understand
      whether this programme is an appropriate warm-up for football players. Results
      were compared with the literature using a meta-analytical approach. Twenty
      amateur male football players [mean age 25.5 (s +/- 5.1) years, body mass 75(8)
      kg, height 181(6) cm] participated in the study. They were tested twice before
      (control period) and once after the "FIFA 11+" for: 20-m sprints, agility,
      vertical jump, stiffness, isometric maximal voluntary contraction (MVC), rate of
      force development (RFD), and star excursion balance test. Oxygen uptake, lactate
      and core temperature were also measured. Pre-post warm-up differences were found
      for all the performance variables (from 1.0 to 6.2%; 0.015 < P < 0.001) with the
      exclusion of MVC (-13%; P = 0.426) and RFD (-10%; P = 0.205). After the warm-up
      there was an increase (0.004 <P < 0.001) in resting oxygen uptake from 325(87) to
      379(142) mL . min(-1), in core temperature from 37.3(0.3) to 37.7(0.3)  degrees
      C, and in lactate from 1.0(0.2) to 2.6(1.1) mmol . L(-1). In conclusion, the
      "FIFA 11+" prevention programme can be considered an appropriate warm-up,
      inducing improvements in football players comparable with those obtained with
      other warm-up routines reported in the literature.

PMID- 23855726
TI  - 'Seeing is Believing'; the use of novel imaging approaches towards creating a
      greater understanding of parasite: host interactions.
AB  - This editorial highlights some of the key points made in the six invited reviews
      in this special issue of Parasite Immunology on the use of contemporary imaging
      technologies to investigate the parasite: host interface. Three of the reviews
      deal with the protozoa Trypanosoma, Leishmania, and Plasmodium, whilst the
      remainder focus on helminth parasites particularly Schistosoma. The reviews cover
      aspects related to how the development of transgenic parasites has vastly
      advanced our understanding of how parasites interact with host cells,
      particularly as a cause of pathology. Imaging technologies have also been
      exploited in revealing parasite localisation within host tissues and identifying
      novel therapeutic targets. Combined the reviews show how 'state of the art'
      imaging technologies have resulted in a seismic advance in our understanding of
      parasite biology and how this has the potential to develop new, and improved,
      strategies to combat disease caused by parasite infections. 

PMID- 23855728
TI  - Delivering and phenotyping mouse models for the respiratory community: a report
      on the Biochemical Society Workshop.
AB  - The IMPC (International Mouse Phenotyping Consortium) was launched recently, and
      its aim is to develop and phenotype mouse knockouts of 4000 genes over the next 5
      years and, ultimately, of all 20000 or so genes in the mouse genome. As part of
      the IMPC, the MRC (Medical Research Council) also launched a call for MRC mouse
      networks, where groups of U.K.-based researchers could form a consortium based
      around a particular area of research. Members of the respiratory research
      community formed the RDDRC (Respiratory Development and Disease Research
      Consortium) to consolidate and develop respiratory phenotyping methods suitable
      for high-throughput screening. This paper, arising from a Biochemical Society
      workshop held in London in 2012, highlights the purposes of the RDDRC and the
      needs of the respiratory research community. 

PMID- 23855729
TI  - Comparison of short- and long-term complications and survival following
      jejunojejunostomy, jejunoileostomy and jejunocaecostomy in 112 horses: 2005-2010.
AB  - REASONS FOR PERFORMING THE STUDY: There is disagreement among surgeons over
      whether jejunoileostomy (JI) or jejunocaecostomy (JC) is the better method of
      anastomosis following proximal ileal resection. OBJECTIVE: To compare short- and
      long-term complications and outcome in horses undergoing jejunojejunostomy (JJ),
      JI and JC and to test the hypotheses that a higher proportion of horses
      undergoing JI would have short-term complications and mortality compared with
      horses undergoing JC or JJ and that JC would be associated with a higher long
      term mortality and occurrence of colic. STUDY DESIGN: Retrospective cross
      sectional study. METHODS: Medical records of horses undergoing celiotomy for a
      small intestinal obstruction and JJ, JI or JC from 2005 to 2010 were reviewed.
      Post operative complications were recorded. Short-term outcome was alive vs. dead
      at hospital discharge and was analysed using a Chi-squared test. Long-term follow
      up was obtained and a Kaplan-Meier estimate of the survivor function was
      performed. RESULTS: There were 112 horses included. A higher proportion of JI
      horses had a repeat celiotomy during hospitalisation compared with horses
      undergoing JC. The number of horses alive at hospital discharge was not different
      between groups: JJ 79% (95% confidence interval [CI] 68-90%), JI 78% (95% CI 61
      96%), JC 83% (95% CI 71-96%). Among horses discharged with long-term follow-up,
      more horses had colic after JC compared with JJ or JI. Long-term post discharge
      survival based on the Kaplan-Meier survivor function was lower for horses
      undergoing JC than JJ or JI (P = 0.04). CONCLUSION: While there was no difference
      in short-term outcome between groups, more horses with JI underwent a repeat
      celiotomy during hospitalisation. Horses with a JC were more likely to have long
      term complications with colic. Horses that were subjected to euthanasia because
      of colic within 12 months of hospital discharge either had a JC or repeat
      celiotomy. The results suggest that, when possible, a JI may be the preferred
      method of anastomosis based on more favourable survival and lower occurrence of
      colic long term.

PMID- 23855730
TI  - Relationship between plasma total homocysteine level and dietary caffeine and
      vitamin B6 intakes in pregnant women.
AB  - A high total homocysteine (tHcy) level during pregnancy is a risk factor for
      adverse perinatal outcomes, such as fetal growth restriction and preeclampsia.
      Caffeine is assumed to increase tHcy levels by acting as a vitamin B6 antagonist.
      The objective of this study was to examine a relationship between circulating
      tHcy levels and dietary caffeine and vitamin B6 intakes in pregnant Japanese
      women. A total of 321 healthy women with singleton pregnancies were recruited in
      metropolitan Tokyo, from June to December 2008, resulting in the final number
      included in the study as 254. Dietary caffeine intakes did not correlate with
      plasma tHcy levels. When we analyzed the data according to caffeinated beverages,
      caffeinated tea consumption was positively associated with plasma tHcy levels
      only among the women with a high intake of vitamin B6 , after controlling for
      confounding factors (P = 0.029). No correlation between coffee consumption and
      plasma tHcy levels was found. Pregnant Japanese women might need to cut down the
      consumption of caffeinated tea as well as take sufficient vitamin B6 in order to
      prevent the tHcy levels from increasing.

PMID- 23855731
TI  - Response to Ayoub: letter to the editor; limitations of radiology in rickets.

PMID- 23855732
TI  - 2011-2012 survey and audit of phototherapy services in the West Midlands, UK.

PMID- 23855733
TI  - Dissecting the large noncovalent protein complex GroEL with surface-induced
      dissociation and ion mobility-mass spectrometry.
AB  - Tandem mass spectrometry is a tool to dissect noncovalent protein complexes into
      smaller substructures for quaternary structure analysis. The commonly used
      activation method, collision induced dissociation (CID), often provides limited
      structural information from the typical dissociation pattern where unfolded
      monomers are ejected from the protein complex. In contrast, surface-induced
      dissociation (SID) has been shown to be very effective at dissociating protein
      complexes with less unfolding than CID. We present here SID of a large
      noncovalent tetradecamer protein, GroEL (801 kDa). A wide variety of products,
      including heptamers representative of the native topology, are released from the
      precursor upon SID, significantly different from the ubiquitous monomer ejection
      in CID. Enhanced dissociation into heptamers is observed when the charge states
      of the GroEL precursor are reduced by adding triethylammonium acetate into the
      spraying buffer. Ion mobility is utilized after SID to separate products
      overlapping in m/z to simplify the SID spectra. Compact heptamers from the charge
      reduced tetradecamer are clearly distinguished from other overlapping species.
      SID can be very useful for quaternary structure studies of large noncovalent
      protein complexes, as manifested by the GroEL data where the tetradecamer
      dissociates into heptamers, reflecting the native topology of the complex. 

PMID- 23855734
TI  - PEG-stabilized core-shell surface-imprinted nanoparticles.
AB  - Here we present a simple technique to produce target-specific molecularly
      imprinted polymeric nanoparticles (MIP NPs) and their surface modification in
      order to prevent the aggregation process that is ever-present in most
      nanomaterial suspensions/dispersions. Specifically, we studied the influence of
      surface modification of MIP NPs with polymerizable poly(ethylene glycol) on their
      degree of stability in water, in phosphate buffer, and in the presence of serum
      proteins. Grafting a polymer shell on the surface of nanoparticles decreases the
      surface energy, enhances the polarity, and as a result improves the
      dispersibility, storage, and colloidal stability as compared to those of core
      (unmodified) particles. Because of the unique solid-phase approach used for
      synthesis, the binding sites of MIP NPs are protected during grafting, and the
      recognition properties of nanoparticles are not affected. These results are
      significant for developing nanomaterials with selective molecular recognition,
      increased biocompatibility, and stability in solution. Materials synthesized this
      way have the potential to be used in a variety of technological fields, including
      in vivo applications such as drug delivery and imaging. 

PMID- 23855735
TI  - Synthesis, characterization, biodegradability and biocompatibility of a
      temperature-sensitive PBLA-PEG-PBLA hydrogel as protein delivery system with low
      critical gelation concentration.
AB  - Temperature-sensitive hydrogels were designed using a series of A-B-A triblock
      copolymers consisting of poly (ethylene glycol) (PEG) with different molecular
      weights as the hydrophilic block B and poly (beta-butyrolactone-co-lactic
      acid)(PBLA) with varying block lengths and composition as the hydrophobic block
      A. The triblock copolymers were synthesized by ring-opening polymerization (ROP)
      of beta-BL and LA in bulk using PEG as an initiator and Sn(Oct)2 as the catalyst.
      Their chemical structure and molecular characteristics were determined by NMR,
      GPC and DSC, and the relationship between structure and phase behaviors in
      aqueous solutions was investigated as well. It was found that the phase behaviors
      in aqueous solutions including critical micelle concentration (CMC), sol-gel
      sedimentation phase transition temperature, gel window width and critical
      gelation concentration (CGC) are largely dependent on the molecular weight and
      block length ratio of PEG/PBLA. Most importantly, they show a very low CGC
      ranging from 4 to 8 wt% because of the introduction of beta-BL. Furthermore, the
      biodegradability and biocompatibility of the hydrogels were evaluated. Finally,
      lysozyme as a model protein was used to evaluate the ability to deliver protein
      drugs in a sustained release manner and biologically active form. All results
      demonstrated that the temperature-sensitive in situ forming hydrogel has a
      promising potential as sustained delivery system for protein drugs.

PMID- 23855736
TI  - Preformulation studies of novel 5'-O-carbonates of lamivudine with biological
      activity: solubility and stability assays.
AB  - As a part of preformulation studies, the aim of this work was to examine the
      solubility and stability of a series of 5'-O-carbonates of lamivudine with proven
      antihuman immunodeficiency virus activity. Solubility studies were carried out
      using pure solvents (water, ethanol and polyethylene glycol 400 [PEG 400]), as
      well as cosolvents in binary mixture systems (water-ethanol and water-PEG 400).
      These ionizable compounds showed that their aqueous solubility is decreasing as
      the carbon length of the substituent moiety increases, but being enhanced as the
      pH was reduced from 7.4 to 1.2. Thus, 3TC-Metha an active compound of the series,
      with an intrinsic solubility at 25  degrees C of 17 mg/mL, was about 70 times
      more soluble than 3TC-Octa (0.24 mg/mL), and at pHs of 1.2, 5.8 and 7.4 had
      intrinsic solubilities of 36.48, 19.20 and 15.40 mg/mL, respectively. In
      addition, the solubility was enhanced significantly by using ethanol and PEG 400
      as cosolvents. A stability study was conducted in buffer solutions at pH 1.2,
      5.8, 7.4 and 13.0 and in human plasma at 37  degrees C. Stability-indicating high
      performance liquid chromatography procedure was found to be selective, sensitive
      and accurate for these compounds and good recovery, linearity and precision were
      also observed.

PMID- 23855737
TI  - Evaluation of biodegradable polyester-co-lactone microparticles for protein
      delivery.
AB  - Abstract Poly(glycerol adipate-co-omega-pentadecalactone) (PGA-co-PDL) was
      previously evaluated for the colloidal delivery of alpha-chymotrypsin. In this
      article, the effect of varying polymer molecular weight (MW) and chemistry on
      particle size and morphology; encapsulation efficiency; in vitro release; and the
      biological activity of alpha-chymotrypsin (alpha-CH) and lysozyme (LS) were
      investigated. Microparticles were prepared using emulsion solvent evaporation and
      evaluated by various methods. Altering the MW or monomer ratio of PGA-co-PDL did
      not significantly affect the encapsulation efficiency and overall poly(1,3
      propanediol adipate-co-omega-pentadecalactone) (PPA-co-PDL) demonstrated the
      highest encapsulation efficiency. In vitro release varied between polymers, and
      the burst release for alpha-CH-loaded microparticles was lower when a higher MW
      PGA-co-PDL or more hydrophobic PPA-co-PDL was used. The results suggest that,
      although these co-polyesters could be useful for protein delivery, little
      difference was observed between the different PGA-co-PDL polymers and PPA-co-PDL
      generally provided a higher encapsulation and slower release of enzyme than the
      other polymers tested. 

PMID- 23855738
TI  - Galacto-oligosaccharides derived from lactulose exert a selective stimulation on
      the growth of Bifidobacterium animalis in the large intestine of growing rats.
AB  - There is increasing interest in identifying novel dietary nondigestible
      carbohydrates capable of modulating the composition and/or metabolic activities
      of the gut microbiota. This work assessed the differential modulatory influence
      of novel galacto-oligosaccharides derived from lactulose (GOS-Lu) in comparison
      with commercial galacto-oligosaccharides derived from lactose (GOS-La) in gut
      microbiota of growing rats (5 weeks old). Rats were fed either a control diet or
      diets containing 1% (w/w) of GOS-Lu or GOS-La, and cecal and colonic contents
      were collected after 14 days of treatment. Compared to controls, GOS-Lu had
      significantly more bifidobacteria within the large intestine, showing a
      significant and selective increase of Bifidobacterium animalis in the cecum and
      colon; however, no significant differences in the number of bifidobacteria among
      GOS-Lu and GOS-La groups were observed. Both types of GOS significantly increased
      the number of the Eubacterium rectale / Clostridium coccoides group. These
      findings support a prebiotic role of galactosyl-fructoses in functional foods. 

PMID- 23855739
TI  - Filling gullies to create farmland on the loess plateau.

PMID- 23855740
TI  - Veterinary trauma centers.

PMID- 23855741
TI  - Incidence of primary cutaneous T-cell lymphoma in Wales.

PMID- 23855742
TI  - Effect of eicosapentaenoic acid agent on aggravated hypertriglyceridemia during
      pregnancy.
AB  - Aggravated hypertriglyceridemia with a serum triglyceride of more than 1000 mg/dL
      is a risk of acute pancreatitis during pregnancy. However, there have been few
      reports on the administration of an eicosapentaenoic acid (EPA) agent for
      aggravated hypertriglyceridemia during pregnancy. A 29-year-old multiparous
      Japanese woman was transferred to our hospital at 29 + 0 weeks of gestation due
      to hypertriglyceridemia of 898 mg/dL. Because diet control was not enough, we
      decided to use an EPA agent, resulting in a reduction in triglyceride levels to
      550 mg/dL. A male infant, weighing 2667 g, was born at 37 + 2 weeks
      transabdominally, and was complicated with respiratory distress syndrome. The
      final diagnosis was type III hyperlipoproteinemia with the apolipoprotein E3/2
      phenotype and a broad beta-migrating lipoprotein on polyacrylamide gel
      electrophoresis of serum lipoproteins. In conclusion, an EPA agent may be a
      possible therapeutic approach for aggravated hypertriglyceridemia during
      pregnancy, although it may increase a risk of respiratory distress syndrome. 

PMID- 23855743
TI  - SNVHMM: predicting single nucleotide variants from next generation sequencing.
AB  - BACKGROUND: The rapid development of next generation sequencing (NGS) technology
      provides a novel avenue for genomic exploration and research. Single nucleotide
      variants (SNVs) inferred from next generation sequencing are expected to reveal
      gene mutations in cancer. However, NGS has lower sequence coverage and poor SNVs
      detection capability in the regulatory regions of the genome. Post probabilistic
      based methods are efficient for detection of SNVs in high coverage regions or
      sequencing data with high depth. However, for data with low sequencing depth, the
      efficiency of such algorithms remains poor and needs to be improved. RESULTS: A
      new tool SNVHMM basing on a discrete hidden Markov model (HMM) was developed to
      infer the genotype for each position on the genome. We incorporated the mapping
      quality of each read and the corresponding base quality on the reads into the
      emission probability of HMM. The context information of the whole observation as
      well as its confidence were completely utilized to infer the genotype for each
      position on the genome in study. Therefore, more probability power can be gained
      over the Bayes based methods, which is very useful for SNVs detection for data
      with low sequencing depth. Moreover, our model was verified by testing against
      two sets of lobular breast tumor and Myelodysplastic Syndromes (MDS) data each.
      Comparing against a recently published SNVs calling algorithm SNVMix2, our model
      improved the performance of SNVMix2 largely when the sequencing depth is low and
      also outperformed SNVMix2 when SNVMix2 is well trained by large datasets.
      CONCLUSIONS: SNVHMM can detect SNVs from NGS cancer data efficiently even if the
      sequence depth is very low. The training data size can be very small for SNVHMM
      to work. SNVHMM incorporated the base quality and mapping quality of all observed
      bases and reads, and also provides the option for users to choose the confidence
      of the observation for SNVs prediction.

PMID- 23855744
TI  - Sporothrix schenckii (sensu strict S. globosa) mating type 1-2 (MAT1-2) gene.
AB  - Sporotix schenckii is a pathogenic fungus that causes human and animal
      sporotrichosis, and based on morphology of the sessile conidia and molecular
      analysis, it was recently recognized as a species complex comprising at least the
      following six sibling species: S. albicans, S. brasiliensis, S. globosa, S.
      luriei, S. mexicana and S. schenckii. However, apart from S. schenckii sensu
      strict, only S. brasiliensis, S. globosa and S. luriei are associated with human
      and animal infection. S. globosa has been most commonly isolated in Asia, Europe
      and the USA; therefore, molecular epidemiological study for S. globosa is
      important in relation to human sporotrichosis in Japan. To the best of our
      knowledge, this is the first study to determine the mating type 1-2 (MAT1-2) gene
      of Sporothrix schenckii with the aim of understanding the taxonomy of the genus
      Sporothrix. The MAT1-2 gene (1618 bp) encodes a protein sequence of 198 amino
      acids. Reverse transcription polymerase chain reaction analysis also detected
      MAT1-2 gene mRNA expression in all of the S. schenckii strains examined,
      indicating that this gene is expressed in S. schenckii cells. Phylogenetic
      analysis of the MAT1-2 gene fragments of Ophiostoma himal-ulmi, O. novo-ulmi, O.
      ulmi and S. schenckii indicated that these isolates could be classified into four
      clusters. MAT1-1 gene-specific polymerase chain reaction was positive in 15
      isolates, but negative in four human isolates and one feline isolate. 

PMID- 23855745
TI  - Artesunate versus quinine in the treatment of severe imported malaria:
      comparative analysis of adverse events focussing on delayed haemolysis.
AB  - BACKGROUND: Severe malaria is a potentially life-threatening infectious disease.
      It has been conclusively shown that artesunate compared to quinine is superior in
      antiparasitic efficacy and in lowering mortality showing a better short-term
      safety profile. Regarding longer-term effects, reports of delayed haemolysis
      after parenteral artesunate for severe malaria in returning travellers have been
      published recently. So far, delayed haemolysis has not been described after the
      use of parenteral quinine. METHODS: In this retrospective study, all patients
      treated for severe malaria at the University Medical Centre Hamburg-Eppendorf
      were included between 2006 and 2012. The primary endpoint was the proportion of
      delayed haemolysis in patients treated with quinine versus those who received
      artesunate. As secondary endpoint, the proportion of any adverse event was
      assessed. RESULTS: A total of 36 patients with severe malaria were included in
      the analysis. Of these, 16 patients contributed sufficient data to assess the
      endpoint delayed haemolysis. Twelve were treated primarily with intravenous
      quinine - with four patients having received intrarectal artesunate as an adjunct
      treatment - and five patients were treated primarily with artesunate. Five cases
      of delayed haemolysis could be detected - two in patients treated with quinine
      and intrarectal artesunate and three in patients treated with artesunate. No case
      of delayed haemolysis was detected in patients treated with quinine alone.While
      adverse events observed in patients treated with artesunate were limited to
      delayed haemolysis (three patients, 60%) and temporary deterioration in renal
      function (three patients, 60%), patients treated with quinine showed a more
      diverse picture of side effects with 22 patients (71%) experiencing at least one
      adverse event. The most common adverse events after quinine were hearing
      disturbances (12 patients, 37%), hypoglycaemia (10 patients, 32%) and
      cardiotoxicity (three patients, 14%). CONCLUSIONS: This study provides further
      evidence on delayed haemolysis after artesunate and underlines the importance of
      a standardized follow-up of patients treated with artesunate for severe malaria.

PMID- 23855746
TI  - Reduced graphene oxide-TaON composite as a high-performance counter electrode for
      Co(bpy)3(3+/2+)-mediated dye-sensitized solar cells.
AB  - We report herein the investigation of TaON nanoparticles incorporating a reduced
      graphene oxide (RGO) nanocomposite as a counter electrode for application in
      Co(bpy)3(3+/2+) (bpy = 2,2'-bipyridine)-mediated dye-sensitized solar cells
      (DSSCs). The RGO-TaON nanocomposite has been prepared by mixing graphene oxide
      (GO) and presynthesized TaON nanoparticles in ethanol/water followed by the
      facile hydrazine hydrate reduction of GO to RGO. Compared with RGO or TaON alone,
      the RGO-TaON nanocomposite shows a much higher electrocatalytic activity for the
      reduction of Co(bpy)3(3+) species owing to synergistic effects, resulting in
      significantly improved solar-cell performance when it is applied as the counter
      electrode in DSSCs. An efficiency of 7.65% for the DSSC with the RGO-TaON counter
      electrode is obtained, competing with the efficiency produced by the Pt counter
      electrode; additionally, the former exhibits a much better electrochemical
      stability than the latter in a Co(bpy)3(3+/2+) acetonitrile solution. 

PMID- 23855747
TI  - Childbearing in adolescence: intergenerational deja-vu? Evidence from a Brazilian
      birth cohort.
AB  - BACKGROUND: Pregnancy in adolescence tends to repeat over generations. This event
      has been little studied in middle and low-income societies undergoing a rapid
      epidemiological transition. To assess this association it is important to adjust
      for socioeconomic conditions at different points in lifetime. Therefore, the aim
      of this study is to analyze the independent effect of adolescent childbearing in
      a generation on its recurrence in the subsequent generation, after adjusting for
      socioeconomic status at different points in life. METHODS: The study was
      conducted on a prospective cohort of singleton liveborn females from the city of
      Ribeirao Preto, Brazil, evaluated in 1978/79, and their daughters assessed in
      2002/04. A total of 1059 mother-daughter pairs were evaluated. The women who had
      their first childbirth before 20 years of age were considered to be adolescent
      mothers. The risk of childbearing in adolescence for the daughter was modeled as
      a function of the occurrence of teenage childbearing in her mother, after
      adjustment for socio-demographic variables in a Poisson regression model.
      RESULTS: The rate of childbearing during adolescence was 31.4% in 1978/79 and
      17.1% in 2002/04. Among the daughters of the 1st generation adolescent mothers,
      this rate was 26.7%, as opposed to 12.7% among the daughters of non adolescent
      mothers. After adjustments the risk of adolescent childbearing for the 2nd
      generation was 35% higher for women whose mothers had been pregnant during
      adolescence - RR = 1.35 (95% CI 1.04-1.74). CONCLUSION: Adolescent childbearing
      in the 1st generation was a predictor of adolescent childbearing in the 2nd,
      regardless of socioeconomic factors determined at different points in lifetime.

PMID- 23855748
TI  - Structure of the transcriptional network controlling white-opaque switching in
      Candida albicans.
AB  - The human fungal pathogen Candida albicans can switch between two phenotypic cell
      types, termed 'white' and 'opaque'. Both cell types are heritable for many
      generations, and the switch between the two types occurs epigenetically, that is,
      without a change in the primary DNA sequence of the genome. Previous work
      identified six key transcriptional regulators important for white-opaque
      switching: Wor1, Wor2, Wor3, Czf1, Efg1, and Ahr1. In this work, we describe the
      structure of the transcriptional network that specifies the white and opaque cell
      types and governs the ability to switch between them. In particular, we use a
      combination of genome-wide chromatin immunoprecipitation, gene expression
      profiling, and microfluidics-based DNA binding experiments to determine the
      direct and indirect regulatory interactions that form the switch network. The six
      regulators are arranged together in a complex, interlocking network with many
      seemingly redundant and overlapping connections. We propose that the structure
      (or topology) of this network is responsible for the epigenetic maintenance of
      the white and opaque states, the switching between them, and the specialized
      properties of each state. 

PMID- 23855749
TI  - Designing a C84 fullerene as a specific voltage-gated sodium channel blocker.
AB  - Fullerene derivatives demonstrate considerable potential for numerous biological
      applications, such as the effective inhibition of HIV protease. Recently, they
      were identified for their ability to indiscriminately block biological ion
      channels. A fullerene derivative which specifically blocks a particular ion
      channel could lead to a new set of drug leads for the treatment of various ion
      channel-related diseases. Here, we demonstrate their extraordinary potential by
      designing a fullerene which mimics some of the functions of MU-conotoxin, a
      peptide derived from cone snail venom which potently binds to the bacterial
      voltage-gated sodium channel (NavAb). We show, using molecular dynamics
      simulations, that the C84 fullerene with six lysine derivatives uniformly
      attached to its surface is selective to NavAb over a voltage-gated potassium
      channel (Kv1.3). The side chain of one of the lysine residues protrudes into the
      selectivity filter of the channel, while the methionine residues located just
      outside of the channel form hydrophobic contacts with the carbon atoms of the
      fullerene. The modified C84 fullerene strongly binds to the NavAb channel with an
      affinity of 46 nM but binds weakly to Kv1.3 with an affinity of 3 mM. This potent
      blocker of NavAb may serve as a structural template from which potent compounds
      can be designed for the targeting of mammalian Nav channels. There is a genuine
      need to target mammalian Nav channels as a form of treatment of various diseases
      which have been linked to their malfunction, such as epilepsy and chronic pain. 

PMID- 23855751
TI  - First total synthesis and stereochemical revision of laxaphycin B and its
      extension to lyngbyacyclamide A.
AB  - The first total synthesis of laxaphycin B was accomplished through stepwise
      automated Solid Phase Peptide Synthesis (SPPS), leading to the structural
      revision of its stereochemistry especially with regard to the configuration of
      one of the two 3-hydroxyleucines of this cyclic dodecapeptide of marine origin.
      The analogous Lyngbyacyclamide A was obtained by an extension of this synthesis. 

PMID- 23855750
TI  - Assessing racial/ethnic disparities in treatment across episodes of mental health
      care.
AB  - OBJECTIVE: To investigate disparities in mental health care episodes, aligning
      our analyses with decisions to start or drop treatment, and choices made during
      treatment. STUDY DESIGN: We analyzed whites, blacks, and Latinos with probable
      mental illness from Panels 9-13 of the Medical Expenditure Panel Survey,
      assessing disparities at the beginning, middle, and end of episodes of care
      (initiation, adequate care, having an episode with only psychotropic drug fills,
      intensity of care, the mixture of primary care provider (PCP) and specialist
      visits, use of acute psychiatric care, and termination). FINDINGS: Compared with
      whites, blacks and Latinos had less initiation and adequacy of care. Black and
      Latino episodes were shorter and had fewer psychotropic drug fills. Black
      episodes had a greater proportion of specialist visits and Latino episodes had a
      greater proportion of PCP visits. Blacks were more likely to have an episode with
      acute psychiatric care. CONCLUSIONS: Disparities in adequate care were driven by
      initiation disparities, reinforcing the need for policies that improve access.
      Many episodes were characterized only by psychotropic drug fills, suggesting
      inadequate medication guidance. Blacks' higher rate of specialist use contradicts
      previous studies and deserves future investigation. Blacks' greater acute mental
      health care use raises concerns over monitoring of their treatment.

PMID- 23855752
TI  - Tephrosia sinapou ethyl acetate extract inhibits inflammatory pain in mice:
      opioid receptor dependent inhibition of TNFalpha and IL-1beta production.
AB  - CONTEXT. Tephrosia toxicaria is currently known as Tephrosia sinapou (Buc'hoz) A.
      Chev. (Fabaceae) and is a source of compounds such as flavonoids that inhibit
      inflammatory pain. OBJECTIVE: To investigate the analgesic effect and mechanisms
      of the ethyl acetate extract of T. sinapou in inflammatory pain in mice.
      MATERIALS AND METHODS: Behavioral responses were evaluated using mechanical (1-24
      h) and thermal hyperalgesia (0.5-5 h), writhing response (20 min) and rota-rod (1
      5 h) tests. Neutrophil recruitment (myeloperoxidase activity), cytokines (tumor
      necrosis factor [TNF]alpha and interleukin [IL]-1beta), aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) serum levels were
      determined by colorimetric assays. Pharmacological treatments were opioid
      receptor antagonist (naloxone, 0.1-1 mg/kg) and control opioid (morphine, 5
      mg/kg). Inflammatory stimuli were carrageenin (100 ug/paw), complete Freund's
      adjuvant (CFA, 10 ul/paw), prostaglandin E2 (PGE2, 100 ng/paw) and acetic acid
      (0.8%). RESULTS: The intraperitoneal pre-treatment with extract inhibited in a
      dose-dependent (30-300 mg/kg) dependent manner the mechanical hyperalgesia
      induced by carrageenin (up to 93% inhibition). The post-treatment (100 mg/kg)
      inhibited CFA-induced hyperalgesia (up to 63% inhibition). Naloxone (1 mg/kg)
      prevented the inhibitory effect of the extract over carrageenin-induced
      mechanical (100%) and thermal (100%) hyperalgesia, neutrophil recruitment (52%)
      and TNFalpha (63%) and IL-1beta (98%) production, thermal threshold in naive mice
      (99%), PGE2-induced mechanical hyperalgesia (88%) and acetic acid-induced
      writhing response (49%). There was no significant alteration in the rota-rod
      test, and AST and ALT serum levels by extract treatment. Discussion and
      conclusion. Tephrosia sinapou ethyl acetate extract reduces inflammatory pain by
      activating an opioid receptor-dependent mechanism.

PMID- 23855753
TI  - Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and
      young infants, a population pharmacokinetic modelling approach.
AB  - Phenobarbital is widely used for treatment of neonatal seizures. Its optimal use
      in neonates and young infants requires information regarding pharmacokinetics.
      The objective of this study is to characterize the absolute bioavailability of
      phenobarbital in neonates and young infants, a pharmacokinetic parameter which
      has not yet been investigated. Routine clinical pharmacokinetic data were
      retrospectively collected from 48 neonates and infants (weight: 0.7-10 kg;
      patient's postnatal age: 0-206 days; GA: 27-42 weeks) treated with phenobarbital,
      who were administered as intravenous or suspension by oral routes and
      hospitalized in a paediatric intensive care unit. Total mean dose of 4.6 mg/kg
      (3.1-10.6 mg/kg) per day was administered by 30-min infusion or by oral route.
      Pharmacokinetic analysis was performed using a nonlinear mixed-effect population
      model software). Data were modelled with an allometric pharmacokinetic model,
      using three-fourths scaling exponent for clearance (CL). The population typical
      mean [per cent relative standard error (%RSE)] values for CL, apparent volume of
      distribution (Vd ) and bioavailability (F) were 0.0054 L/H/kg (7%), 0.64 L/kg
      (15%) and 48.9% (22%), respectively. The interindividual variability of CL, Vd ,
      F (%RSE) and residual variability (%RSE) was 17% (31%), 50% (27%), 39% (27%) and
      7.2 mg/L (29%), respectively. The absolute bioavailability of phenobarbital in
      neonates and infants was estimated. The dose should be increased when switching
      from intravenous to oral administration. 

PMID- 23855754
TI  - Nursing practice environment, quality of care, and morale of hospital nurses in
      Japan.
AB  - The purpose of this study was to describe Japanese hospital nurses' perceptions
      of the nursing practice environment and examine its association with nurse
      reported ability to provide quality nursing care, quality of patient care, and
      ward morale. A cross-sectional survey design was used including 223 nurses
      working in 12 acute inpatient wards in a large Japanese teaching hospital. Nurses
      rated their work environment favorably overall using the Japanese version of the
      Practice Environment Scale of the Nursing Work Index. Subscale scores indicated
      high perceptions of physician relations and quality of nursing management, but
      lower scores for staffing and resources. Ward nurse managers generally rated the
      practice environment more positively than staff nurses except for staffing and
      resources. Regression analyses found the practice environment was a significant
      predictor of quality of patient care and ward morale, whereas perceived ability
      to provide quality nursing care was most strongly associated with years of
      clinical experience. These findings support interventions to improve the nursing
      practice environment, particularly staffing and resource adequacy, to enhance
      quality of care and ward morale in Japan.

PMID- 23855755
TI  - Induction of appropriate Th-cell phenotypes: cellular decision-making in
      heterogeneous environments.
AB  - Helper T (Th)-cell differentiation is a key event in the development of the
      adaptive immune response. By the production of a range of cytokines, Th cells
      determine the type of immune response that is raised against an invading
      pathogen. Th cells can adopt many different phenotypes, and Th-cell phenotype
      decision-making is crucial in mounting effective host responses. This review
      discusses the different Th-cell phenotypes that have been identified and how Th
      cells adopt a particular phenotype. The regulation of Th-cell phenotypes has been
      studied extensively using mathematical models, which have explored the role of
      regulatory mechanisms such as autocrine cytokine signalling and cross-inhibition
      between self-activating transcription factors. At the single cell level, Th
      responses tend to be heterogeneous, but corrections can be made soon after T-cell
      activation. Although pathogens and the innate immune system provide signals that
      direct the induction of Th-cell phenotypes, these instructive mechanisms could be
      easily subverted by pathogens. We discuss that a model of success-driven feedback
      would select the most appropriate phenotype for clearing a pathogen. Given the
      heterogeneity in the induction phase of the Th response, such a success-driven
      feedback loop would allow the selection of effective Th-cell phenotypes while
      terminating incorrect responses.

PMID- 23855756
TI  - Ideal polyethylene nanocrystals.
AB  - The water-soluble catalyst precursor [[(2,4,6-(3,5-(CF3)2C6H3)3-C6H2)-N?C(H)-(3
      (9-anthryl)-2-O-C6H3)-kappa(2)-N,O]Ni(CH3)(TPPTS)] (TPPTS =
      tri(sodiumphenylsulfonate)phosphine) polymerizes ethylene to aqueous dispersions
      of highly ordered nanoscale crystals (crystallinity chi(DSC) >= 90%) of strictly
      linear polyethylene (<0.7 methyl-branches/1000 carbon atoms, Mn = 4.2 * 10(5) g
      mol(-1)). SAXS in combination with cryo-TEM confirms this unusually high degree
      of order (chi(SAXS) = 82%) and shows the nanoparticles to possess a very thin
      amorphous layer on the crystalline lamella, just sufficient to accommodate a
      loop, but likely no entanglements. This ideal chain-folded structure is
      corroborated by annealing studies on the aqueous-dispersed nanoparticles, which
      show that the chain can move through the crystal as evidenced by lamella
      thickening without disturbing the crystalline order as concluded from an
      unaltered low thickness of the amorphous layers. These ideal chain-folded
      polyethylene nanocrystals arise from the crystallization in the confined
      environment of a nanoparticle and a deposition of the growing polymer chain on
      the crystal growth front as the chain is formed by the catalyst. 

PMID- 23855757
TI  - Application of dissolvable layered double hydroxides as sorbent in dispersive
      solid-phase extraction and extraction by co-precipitation for the determination
      of aromatic acid anions.
AB  - Three types of magnesium-aluminum layered double hydroxides were synthesized and
      employed as solid-phase extraction (SPE) sorbents to extract several aromatic
      acids (protocatechuic acid, mandelic acid, phthalic acid, benzoic acid, and
      salicylic acid) from aqueous samples. An interesting feature of these sorbents is
      that they dissolve when the pH of the solution is lower than 4. Thus, the analyte
      elution step, as needed in conventional sorbent-based extraction, was obviated by
      dissolving the sorbent in acid after extraction and separation from the sample
      solution. The extract was then directly injected into a high-performance liquid
      chromatography-ultraviolet detection system for analysis. In the key adsorption
      process, both dispersive SPE and co-precipitation extraction with the sorbents
      were conducted and experimental parameters such as pH, temperature, and
      extraction time were optimized. The results showed that both extraction methods
      provided low limits of detection (0.03-1.47 MUg/L) and good linearity (r(2) >
      0.9903). The optimized extraction conditions were applied to human urine and
      sports drink samples. This new and interesting extraction approach was
      demonstrated to be a fast and efficient procedure for the extraction of organic
      anions from aqueous samples. 

PMID- 23855758
TI  - Nodal reactive and neoplastic proliferation of monocytoid and marginal zone B
      cells: an immunoarchitectural and molecular study highlighting the relevance of
      IRTA1 and T-bet as positive markers.
AB  - AIMS: Marginal zone B cells (MZCs) and monocytoid B cells (MBCs) appear to be
      related lymphoid cells that take part in reactive and neoplastic marginal zone
      proliferations. These lesions are not yet well characterized, and the aim of this
      study was to find better diagnostic criteria for them. METHODS AND RESULTS: We
      analysed 60 nodal lesions with MBC and/or MZC proliferation for their
      morphological, immunophenotypic, molecular genetic and IG gene rearrangement
      features. On the basis of the results of the rearrangement assay and
      immunoglobulin light chain restriction, the lesions were divided into reactive
      and neoplastic groups. Among the neoplastic lesions, polymorphic and monomorphic
      subgroups emerged. All reactive lesions had morphological features of the
      polymorphic subgroup. By immunohistochemistry, IRTA1 and/or T-bet expression was
      found in all reactive lesions and in 90% of neoplastic lesions. CONCLUSIONS:
      IRTA1 and T-bet are positive markers for the identification of MZC/MBC
      proliferations, and thus for the diagnosis of nodal marginal zone lymphoma
      (NMZL). Polymorphic and monomorphic subgroups of NMZL could be distinguished.
      Most morphological and immunophenotypic patterns in reactive and neoplastic nodal
      expansions of MZCs and MBCs overlapped. Therefore, PCR clonality assay of the
      immunoglobulin heavy and light chain gene loci is the most reliable method for
      their differentiation.

PMID- 23855759
TI  - Impact of bispectral index for monitoring propofol remifentanil anaesthesia. A
      randomised clinical trial.
AB  - BACKGROUND: Previous research has shown that the use of the bispectral index
      (BIS) monitor to measure the depth of anaesthesia reduces the amount of
      anaesthetics administered and the recovery time from general anaesthesia. The
      effect of BIS on recovery from anaesthesia and consumption of anaesthetics in a
      paediatric population receiving total intravenous anaesthesia (TIVA) with
      propofol and remifentanil has not been studied. METHODS: A single-blind, single
      centre clinical trial. One hundred fifty-seven patients were enrolled. They were
      scheduled for ear, nose, and throat surgery and stratified according to age
      groups (1-3 years, 4-11 years, 12-17 years, 18-65 years) and type of operation,
      yielding a total of nine subgroups. Patients were randomly allocated to receive
      either a TIVA with propofol and remifentanil according to conventional clinical
      practice (control) or guided by BIS. Normalised propofol (MUg/kg/min) and
      remifentanil (MUg/kg/min) consumption and time to extubation (s) were the outcome
      measures. RESULTS: Children aged 1-3 years in the BIS group had a longer time to
      extubation compared with controls (P: 0.04). Patients aged 12-17 years in the BIS
      group received higher maintenance infusion rates of propofol compared with
      controls (P = 0.02). No significant difference for the outcome variables was
      evidenced in the other age groups. CONCLUSION: BIS monitoring for guidance of
      propofol-remifentanil anaesthesia does not result in reduced consumption of
      anaesthetics and does not reduce time to extubation in adult and children
      compared with conventional practice.

PMID- 23855760
TI  - From regained function to daily use: experiences of surgical reconstruction of
      grip in people with tetraplegia.
AB  - PURPOSE: To capture patients' relearning processes from regained function to
      improvements in daily life after grip reconstructive surgery in tetraplegia.
      SUBJECTS: Eleven people with tetraplegia who underwent grip reconstructive
      surgery during February 2009 to March 2011. METHODS: Qualitative interviews were
      conducted 7 to 17 months after surgery and analysed using grounded theory.
      RESULTS: Determination to reach a higher level of independence was the core
      concept to integrate regained function into daily life. There were 3 phases
      identified; "Initiate activity training," "Establish hand control in daily
      activities," and "Challenge dependence." Between the phases psychological stages
      occurred, first; "a belief in improved ability", and later in the process;
      "confidence in ability". The process to fully integrate regain function in daily
      life was described as long and time-consuming. However, the participants claimed
      it useful to do the skills training in their home environment, without long-term
      in clinic rehabilitation. CONCLUSION: Relearning activities in daily life after a
      grip reconstruction is a time-consuming and demanding process. It includes skills
      training, mental strategies and psychological stages together with environmental
      and social factors. Accordingly, rehabilitation after grip reconstruction in
      tetraplegia should focus on both grip skills and psychological stages, to
      encourage that patient's keep their determination and achieve greater
      independence. Implications for Rehabilitation There is a stepwise process to
      transform improved function into daily use. The most important factor to
      transform improved function into daily use was motivation to reach a higher
      independence. Other important factors were; skills training, use of individual
      learning strategies, belief and confidence in personal ability, social and
      environmental factors. There was a long and demanding process to fully transform
      the improved function into daily use. The participants preferred to do activity
      training in the specific environment, usually at home.

PMID- 23855761
TI  - Effect of tofacitinib, a Janus kinase inhibitor, on haematological parameters
      during 12 weeks of psoriasis treatment.
AB  - BACKGROUND: The Janus kinase (JAK) inhibitor, tofacitinib, has shown efficacy for
      the treatment of psoriasis in a phase IIb trial (A3921047; NCT00678210).
      OBJECTIVES: To report haematology data from the phase IIb trial, given the
      importance of JAK-dependent signalling in haematopoiesis. METHODS: Patients with
      moderate-to-severe chronic plaque psoriasis were randomized to receive
      tofacitinib 2, 5 or 15 mg, or placebo, twice daily over 12 weeks. Blood samples
      were collected at screening, baseline, weeks 2, 4, 8 and 12 during treatment, and
      weeks 14 and 16 during off-treatment follow-up. RESULTS: Baseline haematology was
      similar across patients receiving tofacitinib 2 mg (n = 49), 5 mg (n = 49) or 15
      mg (n = 49), or placebo (n = 50). Tofacitinib conferred dose-dependent decreases
      in haemoglobin, haematocrit and red blood cell counts, while reticulocyte counts
      initially declined, before recovering by week 8, and exceeding baseline levels
      after treatment cessation. With regard to white blood cells, tofacitinib had no
      clear dose-dependent effects on basophils or monocytes, but appeared to be
      associated with transient or reversible dose-dependent decreases in neutrophil
      and eosinophil counts and transient increases in lymphocyte counts, which were
      primarily attributable to increases in B-cell counts. Natural killer cell counts
      declined with tofacitinib. CONCLUSIONS: Tofacitinib conferred tolerable, dose
      dependent changes in haematological parameters during short-term administration
      in patients with psoriasis. The effects did not appear to be progressive, and
      were often transient or reversible.

PMID- 23855762
TI  - Hypaphorine is present in human milk in association with consumption of legumes.
AB  - In metabolomic analysis of human milk amines, we found a previously unidentified
      compound. This was tentatively identified as hypaphorine, an indole alkaloid
      composed of tryptophan and three methyls, and with neurological and glucose
      lowering effects in rodents. Hypaphorine identity was confirmed by hypaphorine
      synthesis, and then a fluorometric method was developed to quantify hypaphorine
      in milk and foods. Using dietary records, we identified peanut products as
      probable sources of hypaphorine. Milk from 24 lactating women showed widely
      varying hypaphorine, with a mean +/- SD 0.34 +/- 0.33 MUM, and the highest
      concentration of 1.24 MUM. Peanuts showed high hypaphorine of 70 MUg/g compared
      to 60 and 100 MUg/g in dried chickpeas and lentils. Dietary challenge in
      lactating women with hypaphorine-rich foods demonstrated transfer of hypaphorine
      into milk with hypaphorine appearance peaking 5-18 h after consumption and
      prolonged disappearance indicative of slow excretion or metabolism. The potential
      functional roles of hypaphorine in human nutrition remain to be addressed. 

PMID- 23855764
TI  - Physiological and performance responses to the FIFA 11+ (part 2): a randomised
      controlled trial on the training effects.
AB  - The aim of this study was to examine the training effects of an injury prevention
      programme on neuromuscular control, strength and performance in male amateur
      football players. Eighty-one players were allocated to the "FIFA 11+" (n = 42) or
      a control group (CON, n = 39). The "FIFA 11+" group performed the programme 3
      times a week for 9 weeks; the control group completed the usual warm-up. Primary
      outcomes were: time-to-stabilisation test and eccentric/concentric flexors
      strength. Secondary outcomes were: eccentric/concentric extensors strength, star
      excursion balance test, core-stability test, vertical jump, sprint, and agility.
      After controlling for covariates, significant between-group differences after the
      intervention (in favour of the "FIFA 11+" players) were found for time-to
      stabilisation (-2.8%, 90% confidence interval [CI] -4.4 to -1.2%) and core
      stability (-8.9%, -14.6 to -3.1%). Differences were also found for eccentric
      (3.8%, 1.4 to 6.2%) and concentric flexors strength (3.2%, 0.6 to 5.9%) at 60
      degrees  . s(-1) but this difference was only possibly meaningful (62.4%) from a
      practical point of view. No substantial and/or significant differences were found
      for the other outcomes. Performing "FIFA 11+" for 9 weeks can improve
      neuromuscular control. Possible worthwhile differences were found for flexors
      strength but there were no substantial effects in the other performance measures.

PMID- 23855763
TI  - Effect of Danofloxacin on Reactive Oxygen Species Production, Lipid Peroxidation
      and Antioxidant Enzyme Activities in Kidney Tubular Epithelial Cell Line, LLC
      PK1.
AB  - The purpose of this study was to investigate the possibility that oxidative
      stress was involved in danofloxacin-induced toxicity in renal tubular cells
      epithelial cell line (LLC-PK1). Confluent LLC-PK1 cells were incubated with
      various concentrations of danofloxacin. The extent of oxidative damage was
      assessed by measuring the reactive oxygen species (ROS) level, lipid
      peroxidation, cell apoptosis and antioxidative enzyme activities. Danofloxacin
      induced a concentration-dependent increase in the ROS production, not even
      cytotoxic conditions. Similarly, danofloxacin caused an about 4 times increase in
      the level of thiobarbituric acid reactive substances at the concentration of 400
      MUM for 24 hr, but it did not induce cytotoxicity and apoptosis. Antioxidant
      enzymes activities, such as superoxide dismutase (SOD) and catalase (CAT), were
      increased after treatment with 100, 200 and 400 MUM of danofloxacin for 24 hr.
      The activity of glutathione peroxidase (GPX) was significantly decreased in a
      concentration-dependent manner. In addition, ROS production, lipid peroxidation
      and GPX decline were inhibited by additional glutathione and N-acetyl cysteine.
      These data suggested that danofloxacin could not induce oxidative stress in LLC
      PK1 cells at the concentration (<=400 MUM) for 24 hr. The increase levels of ROS
      and lipid peroxidation could be partly abated by the increase activities of SOD
      and CAT. 

PMID- 23855765
TI  - Ovarian transposition before pelvic irradiation: indications and functional
      outcome.
AB  - AIM: To investigate the indications and effectiveness of ovarian transposition
      before pelvic irradiation. METHODS: This was a retrospective analysis of patients
      with malignancies who underwent ovarian transposition before pelvic irradiation.
      The collected data included age of patient, type and stage of cancer, details of
      irradiation treatment, and clinical and biochemical parameters of ovarian
      function during the period of follow-up. RESULTS: Fourteen adult and four
      pediatric patients with different types of cancers underwent ovarian
      transposition during the study period. The common tumor types for the adult
      patients were cervical cancer (n = 4), rectal cancer (n = 4) and medulloblastoma
      (n = 3), and for pediatric patients was medulloblastoma (n = 2). The mean age for
      adult patients was 31 years (range, 21-40) and for pediatric patients was 7 years
      (range, 4-10). Of the adult patients, 10 had adjuvant chemotherapy and four had
      neoadjuvant chemotherapy added to their radiotherapy program. All pediatric
      patients received adjuvant chemotherapy. Thirteen of 14 (92.85%) adult patients
      had normal serum level of follicle-stimulating hormone (FSH; <=12 IU/L) and E2
      (>50 pg/mL). Only one patient had premature menopause. All pediatric patients
      demonstrated a normal serum level of FSH (<12) and E2 for their age at 3 and 6
      months after completion of their treatment. The mean follow-up was 42 months
      (range, 34-50). CONCLUSION: Ovarian transposition is an effective procedure for
      the preservation of ovarian function. Young patients with non-hormone-dependent
      pelvic tumors should be offered a laparoscopic ovarian transposition before the
      start of pelvic radiotherapy.

PMID- 23855767
TI  - How to fail at species delimitation.
AB  - Species delimitation is the act of identifying species-level biological
      diversity. In recent years, the field has witnessed a dramatic increase in the
      number of methods available for delimiting species. However, most recent
      investigations only utilize a handful (i.e. 2-3) of the available methods, often
      for unstated reasons. Because the parameter space that is potentially relevant to
      species delimitation far exceeds the parameterization of any existing method, a
      given method necessarily makes a number of simplifying assumptions, any one of
      which could be violated in a particular system. We suggest that researchers
      should apply a wide range of species delimitation analyses to their data and
      place their trust in delimitations that are congruent across methods.
      Incongruence across the results from different methods is evidence of either a
      difference in the power to detect cryptic lineages across one or more of the
      approaches used to delimit species and could indicate that assumptions of one or
      more of the methods have been violated. In either case, the inferences drawn from
      species delimitation studies should be conservative, for in most contexts it is
      better to fail to delimit species than it is to falsely delimit entities that do
      not represent actual evolutionary lineages. 

PMID- 23855768
TI  - A two-dimensional oxamate- and oxalate-bridged Cu(II)Mn(II) motif: crystal
      structure and magnetic properties of (Bu4N)2[Mn2{Cu(opba)}2ox].
AB  - A new compound of formula (Bu4N)2[Mn2{Cu(opba)}2ox] (1) [Bu4N(+) = tetra-n
      butylammonium cation, H4opba = 1,2-phenylenebis(oxamic acid), and H2ox = oxalic
      acid] has been synthesized and magneto-structurally investigated. The reaction of
      manganese(II) acetate, [Cu(opba)](2-), and ox(2-) in dimethyl sulfoxide yielded
      single crystals of 1. The structure of 1 consists of heterobimetallic oxamato
      bridged Cu(II)Mn(II) chains which are connected through bis-bidentate oxalate
      coordinated to the manganese(II) ions to afford anionic heterobimetallic layers
      of 6(3)-hcb net topology. The layers are interleaved by n-Bu4N(+) counterions.
      Each copper(II) ion in 1 is four-coordinate in a square planar environment
      defined by two amidate-nitrogen and two carboxylate-oxygen atoms from the two
      oxamate groups of the obpa ligand. The manganese(II) ion is six-coordinate in a
      somewhat distorted octahedral surrounding that is built by two oxalate-oxygen and
      four carbonyl-oxygen atoms from two [Cu(opba)](2-) units. The magnetic properties
      of 1 in the temperature range 1.9-300 K correspond to those expected for the
      coexistence of intralayer antiferromagnetic interactions of the type copper(II)
      manganese(II) across oxamato and manganese(II)-manganese(II) through oxalato
      bridges plus a weak spin canting in the very low temperature domain. Simulation
      of the magnetic data through quantum Monte Carlo methodology reveals the
      magnitude of the intralayer magnetic interactions [J(CuMn) = -32.5(3) cm(-1), and
      J(MnMn) = -2.7(3) cm(-1)], their values being within the range of those
      previously observed in lower nuclearity systems.

PMID- 23855770
TI  - Evolutionary variation in the mechanics of fiddler crab claws.
AB  - BACKGROUND: Fiddler crabs, genus Uca, are classic examples of how intense sexual
      selection can produce exaggerated male traits. Throughout the genus the enlarged
      "major" cheliped (claw) of the male fiddler crab is used both as a signal for
      attracting females and as a weapon for combat with other males. However, the
      morphology of the major claw is highly variable across the approximately 100
      species within the genus. Here we address variation, scaling, and correlated
      evolution in the mechanics of the major claw by analyzing the morphology and
      mechanical properties of the claws of 21 species of fiddler crabs from the
      Pacific, Gulf and Atlantic coasts of the Americas. RESULTS: We find that the
      mechanics that produce claw closing forces, the sizes of claws and the mechanical
      strength of the cuticle of claws are all highly variable across the genus. Most
      variables scale isometrically with body size across species but claw force
      production scales allometrically with body size. Using phylogenetically
      independent contrasts, we find that the force that a claw can potentially produce
      is positively correlated with the strength of the cuticle on the claw where
      forces are delivered in a fight. There is also a negative correlation between the
      force that a claw can potentially produce and the size of the claw corrected for
      the mass of the claw. CONCLUSIONS: These relationships suggest that there has
      been correlated evolution between force production and armoring, and that there
      is a tradeoff between claw mechanics for signaling and claw mechanics for
      fighting.

PMID- 23855769
TI  - Adenosine A2B receptor and hyaluronan modulate pulmonary hypertension associated
      with chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
      worldwide. The development of pulmonary hypertension (PH) in patients with COPD
      is strongly associated with increased mortality. Chronic inflammation and changes
      to the lung extracellular matrix (ECM) have been implicated in the pathogenesis
      of COPD, yet the mechanisms that lead to PH secondary to COPD remain unknown. Our
      experiments using human lung tissue show increased expression levels of the
      adenosine A2B receptor (ADORA2B) and a heightened deposition of hyaluronan (HA; a
      component of the ECM) in remodeled vessels of patients with PH associated with
      COPD. We also demonstrate that the expression of HA synthase 2 correlates with
      mean pulmonary arterial pressures in patients with COPD, with and without a
      secondary diagnosis of PH. Using an animal model of airspace enlargement and PH,
      we show that the blockade of ADORA2B is able to attenuate the development of a PH
      phenotype that correlates with reduced levels of HA deposition in the vessels and
      the down-regulation of genes involved in the synthesis of HA. 

PMID- 23855771
TI  - Nanoscale contact mechanics of biocompatible polyzwitterionic brushes.
AB  - Friction force microscopy has been used to demonstrate that biocompatible,
      lubricious poly(2-(methacryloyloxy)ethylphosphorylcholine) (PMPC) brushes exhibit
      different frictional properties depending on the medium (methanol, ethanol, 2
      propanol, and water; the latter also with different quantities of added salt).
      The chemical functionalization of the probe (amine-, carboxylic acid-, and methyl
      terminated probes were used) is not as important as the medium in determining the
      contact mechanics. For solvents such as methanol, where the adhesion between AFM
      probe and PMPC brushes is negligible, a linear friction-load relationship is
      observed. In contrast, the friction-load plot is nonlinear in ethanol or water,
      media in which stronger adhesion is measured. For ethanol, the data indicate
      Johnson-Kendall-Roberts (JKR) mechanics, whereas the Derjaguin-Muller-Toporov
      (DMT) model provided a good fit for the data acquired in water. Contact mechanics
      on zwitterionic PMPC brushes immersed in aqueous solutions of varying ionic
      strength followed the same trend, with high adhesion energies being correlated
      with a nonlinear friction-load relationship. These results can be rationalized by
      treating the friction force as the sum of a load-dependent term, attributed to
      molecular plowing, and an area-dependent shear term. In a good solvent for PMPC
      such as methanol, the shear term is negligible and the sliding interaction is
      dominated by molecular plowing. However, the adhesion energy is significantly
      larger in water and ethanol and the shear term is no longer negligible. 

PMID- 23855772
TI  - In vivo bone strain and finite element modeling of the mandible of Alligator
      mississippiensis.
AB  - Forces experienced during feeding are thought to strongly influence the
      morphology of the vertebrate mandible; in vivo strain data are the most direct
      evidence for deformation of the mandible induced by these loading regimes.
      Although many studies have documented bone strains in the mammalian mandible, no
      information is available on strain magnitudes, orientations or patterns in the
      sauropsid lower jaw during feeding. Furthermore, strain gage experiments record
      the mechanical response of bone at a few locations, not across the entire
      mandible. In this paper, we present bone strain data recorded at various sites on
      the lower jaw of Alligator mississippiensis during in vivo feeding experiments.
      These data are used to understand how changes in loading regime associated with
      changes in bite location are related to changes in strain regime on the working
      and balancing sides of the mandible. Our results suggest that the working side
      mandible is bent dorsoventrally and twisted about its long-axis during biting,
      and the balancing side experiences primarily dorsoventral bending. Strain
      orientations are more variable on the working side than on the balancing side
      with changes in bite point and between experiments; the balancing side exhibits
      higher strain magnitudes. In the second part of this paper, we use principal
      strain orientations and magnitudes recorded in vivo to evaluate a finite element
      model of the alligator mandible. Our comparison demonstrates that strain
      orientations and mandibular deformation predicted by the model closely match in
      vivo results; however, absolute strain magnitudes are lower in the finite element
      model. 

PMID- 23855773
TI  - Efficacy and safety of targeted narrowband ultraviolet B therapy using a flat
      type fluorescent lamp for the treatment of palmoplantar pustulosis.

PMID- 23855775
TI  - All-optical technique to correlate defect structure and carrier transport in
      transferred graphene films.
AB  - Chemical vapor deposition of graphene on copper foil is an attractive method of
      producing large-area graphene films, but the electronic performance is limited by
      defects such as creases from the film transfer process, wrinkles due to the
      thermal expansion coefficient mismatch, and grain boundaries from the growth
      process. Here we present an all-optical technique to correlate defect structure
      with electronic properties using spatially resolved Raman spectroscopy and
      transient absorption microscopy. This technique is especially attractive since it
      does not require any lithographic steps to probe the electronic properties of the
      graphene film. As a first demonstration, we focus on the effects of both wrinkles
      and creases while averaging over many small grains. It was found that wrinkles
      and creases may decrease the charge carrier diffusion coefficient by over 50% due
      to increased defect scattering. This technique may easily be extended to large
      grain graphene films in order to study the effect of different types of grain
      boundaries. 

PMID- 23855774
TI  - FtsEX is required for CwlO peptidoglycan hydrolase activity during cell wall
      elongation in Bacillus subtilis.
AB  - The peptidoglycan (PG) sacculus, a meshwork of polysaccharide strands cross
      linked by short peptides, protects bacterial cells against osmotic lysis. To
      enlarge this covalently closed macromolecule, PG hydrolases must break peptide
      cross-links in the meshwork to allow insertion of new glycan strands between the
      existing ones. In the rod-shaped bacterium Bacillus subtilis, cell wall
      elongation requires two redundant endopeptidases, CwlO and LytE. However, it is
      not known how these potentially autolytic enzymes are regulated to prevent lethal
      breaches in the cell wall. Here, we show that the ATP-binding cassette
      transporter-like FtsEX complex is required for CwlO activity. In Escherichia
      coli, FtsEX is thought to harness ATP hydrolysis to activate unrelated PG
      hydrolases during cell division. Consistent with this regulatory scheme, B.
      subtilis FtsE mutants that are unable to bind or hydrolyse ATP cannot activate
      CwlO. Finally, we show that in cells depleted of both CwlO and LytE, the PG
      synthetic machinery continues moving circumferentially until cell lysis,
      suggesting that cross-link cleavage is not required for glycan strand
      polymerization. Overall, our data support a model in which the FtsEX complex is a
      remarkably flexible regulatory module capable of controlling a diverse set of PG
      hydrolases during growth and division in different organisms.

PMID- 23855776
TI  - Family planning practices and pregnancy intentions among HIV-positive and HIV
      negative postpartum women in Swaziland: a cross sectional survey.
AB  - BACKGROUND: In settings where sexually transmitted infection (STI) and HIV
      prevalence is high, the postpartum period is a time of increased biological
      susceptibility to pregnancy related sepsis. Enabling women living with HIV to
      avoid unintended pregnancies during the postpartum period can reduce vertical
      transmission and maternal mortality associated with HIV infection. We describe
      family planning (FP) practices and fertility desires of HIV-positive and HIV
      negative postpartum women in Swaziland. METHODS: Data are drawn from a baseline
      survey of a four-year multi country prospective cohort study under the Integra
      Initiative, which is measuring the benefits and costs of providing integrated HIV
      and sexual and reproductive health (SRH) services in Kenya and Swaziland. We
      compare data from 386 HIV-positive women and 483 HIV-negative women recruited in
      Swaziland between February and August 2010. Data was collected on hand-held
      personal digital assistants (PDAs) covering fertility desires, mistimed or
      unwanted pregnancies and contraceptive use prior to their most recent pregnancy.
      Data were analysed using Stata 10.0. Descriptive statistics were conducted using
      the chi square test for categorical variables. Measures of effect were assessed
      using multivariate fixed effects logistic regression model accounting for
      clustering at facility level and the results are presented as adjusted odds
      ratios. RESULTS: Majority (69.2%) of postpartum women reported that their most
      recent pregnancy was unintended with no differences between HIV-positive and HIV
      negative women: OR: 0.96 (95% CI) (0.70, 1.32). Although, there were significant
      differences between HIV-positive and HIV-negative women who reported that their
      previous pregnancy was unwanted, (20.7% vs. 13.5%, p = 0.004), when adjusted this
      was not significant OR: 1.43 (0.92, 1.91). 47.2% of HIV-positive women said it
      was mistimed compared to 52.5%, OR: 0.79 (0.59, 1.06). 37.9% of all women said
      they do not want another child. Younger women were more likely to have unwanted
      pregnancies: OR: 1.12 (1.07, 1.12), while they were less likely to have mistimed
      births; OR: 0.82 (0.70, 0.97). Those with tertiary education were less likely to
      have unwanted or mistimed pregnancies OR: 0.30 (0.11, 0.86). Half of HIV-positive
      women and more than a third of HIV-negative women reported that they had been
      using a FP method when they became pregnant with no differences between the
      groups: OR: 1.61 (0.82,3.41). Only short-acting methods were available to these
      women before the most recent pregnancy; and available during the postpartum
      visit. One fifth of all women received an FP method during the current visit.
      Among the four fifths who did not receive a method 17.3% reported they were
      already using a method or were breastfeeding. HIV-positive women were more likely
      to have already started a method than HIV-negative women (20% vs. 15%, p =
      0.089). CONCLUSION: There are few differences overall between the experiences of
      both HIV-positive and negative women in terms of FP experiences, unintended
      pregnancy and services received during the early postpartum period in Swaziland.
      Women attending postpartum facilities are receiving satisfactory care. Access to
      a wider range of effective methods is urgently needed if high levels of
      unintended pregnancy are to be reduced among HIV-positive and HIV-negative women
      living in Swaziland.

PMID- 23855777
TI  - The triterpenoid fraction from Trichosanthes dioica root suppresses
      experimentally induced inflammatory ascites in rats.
AB  - CONTEXT: Trichosanthes dioica Roxb. (Cucurbitaceae), called pointed gourd in
      English, is a dioecious climber found wild throughout the plains of the Indian
      subcontinent and traditionally used in India for several medicinal purposes.
      OBJECTIVE: The present study evaluated the protective effect of the triterpenoid
      enriched fraction from T. dioica root (CETD) against experimentally induced acute
      inflammatory ascites in Wistar albino rats. MATERIALS AND METHODS: The CETD was
      administered orally at the different doses (25, 50 and 100 mg/kg body weight) to
      overnight fasted rats, and then ascites was induced by intraperitoneal
      administration of formalin solution. After 7 h, the rats were sacrificed and the
      volume of ascitic fluid was measured. RESULTS: The CETD demonstrated significant
      (p < 0.01) reduction of ascitic fluid formation in a dose-dependent manner as
      compared with control. CONCLUSION: The CETD produced significant and dose
      dependent inhibition of experimentally induced inflammatory ascites in Wistar
      albino rats.

PMID- 23855778
TI  - Physical durability of PermaNet 2.0 long-lasting insecticidal nets over three to
      32 months of use in Ethiopia.
AB  - BACKGROUND: Ethiopia scaled up net distribution markedly starting in 2006.
      Information on expected net life under field conditions (physical durability and
      persistence of insecticidal activity) is needed to improve planning for net
      replacement. Standardization of physical durability assessment methods is
      lacking. METHODS: Permanet(r)2.0 long-lasting insecticidal bed nets (LLINs),
      available for distribution in early 2007, were collected from households at three
      time intervals. The number, size and location of holes were recorded for 189 nets
      used for three to six months from nine sites (2007) and 220 nets used for 14 to
      20 months from 11 sites (2008). In 2009, a "finger/fist" sizing method classified
      holes in 200 nets used for 26 to 32 months from ten sites into small (<2 cm),
      medium (> = 2 to < =10 cm) and large (>10 cm) sizes. A proportionate hole index
      based on both hole number and area was derived from these size classifications.
      RESULTS: After three to six months, 54.5% (95% CI 47.1-61.7%) of 189 LLINs had at
      least one hole 0.5 cm (in the longest axis) or larger; mean holes per net was 4.4
      (SD 8.4), median was 1.0 (Inter Quartile Range [IQR] 0-5) and median size was 1
      cm (IQR 1-2). At 14 to 20 months, 85.5% (95% CI 80.1-89.8%) of 220 nets had at
      least one hole with mean 29.1 (SD 50.1) and median 12 (IQR 3-36.5) holes per net,
      and median size of 1 cm (IQR 1-2). At 26 to 32 months, 92.5% of 200 nets had at
      least one hole with a mean of 62.2 (SD 205.4) and median of 23 (IQR 6-55.5) holes
      per net. The mean hole index was 24.3, 169.1 and 352.8 at the three time periods
      respectively. Repairs were rarely observed. The majority of holes were in the
      lower half of the net walls. The proportion of nets in 'poor' condition (hole
      index >300) increased from 0% at three to six months to 30% at 26 to 32 months.
      CONCLUSIONS: Net damage began quickly: more than half the nets had holes by three
      to six months of use, with 40% of holes being larger than 2 cm. Holes continued
      to accumulate until 92.5% of nets had holes by 26 to 32 months of use. An almost
      complete lack of repairs shows the need for promoting proper use of nets and
      repairs, to increase LLIN longevity. Using the hole index, almost one third of
      the nets were classed as unusable and ineffective after two and a half years of
      potential use.

PMID- 23855779
TI  - Polyacrylamide gel with switchable trypsin activity for analysis of proteins.
AB  - Trypsin was immobilized on a variety of materials to improve digestion
      efficiency. However, because the immobilized trypsin will digest proteins during
      electrophoresis, direct immobilization of active trypsin in polyacrylamide gel
      will compromise the protein separation. To overcome this problem, here we report
      a novel polyacrylamide gel with switchable trypsin activity. It was prepared by
      copolymerization of the PEG-trypsin-aprotinin complex during the gel-casting
      step. Because the inhibitor aprotinin binds strongly with trypsin at alkaline pH,
      this novel gel does not display hydrolytic activity during electrophoresis. After
      electrophoresis, the activity of trypsin embedded in gel could be recovered by
      simply washing away the bound inhibitor at a low pH. It was demonstrated that
      this unique switchable activity design allowed high resolution of the complex
      protein mixture during electrophoresis and highly efficient digestion of the
      separated proteins in situ in the gel after electrophoresis. 

PMID- 23855780
TI  - Article removed: Severe contact dermatitis due to camomile: a common
      complementary remedy with potential sensitization risks.

PMID- 23855781
TI  - Toward an ideal polymer binder design for high-capacity battery anodes.
AB  - The dilemma of employing high-capacity battery materials and maintaining the
      electronic and mechanical integrity of electrodes demands novel designs of binder
      systems. Here, we developed a binder polymer with multifunctionality to maintain
      high electronic conductivity, mechanical adhesion, ductility, and electrolyte
      uptake. These critical properties are achieved by designing polymers with proper
      functional groups. Through synthesis, spectroscopy, and simulation, electronic
      conductivity is optimized by tailoring the key electronic state, which is not
      disturbed by further modifications of side chains. This fundamental allows
      separated optimization of the mechanical and swelling properties without
      detrimental effect on electronic property. Remaining electronically conductive,
      the enhanced polarity of the polymer greatly improves the adhesion, ductility,
      and more importantly, the electrolyte uptake to the levels of those available
      only in nonconductive binders before. We also demonstrate directly the
      performance of the developed conductive binder by achieving full-capacity cycling
      of silicon particles without using any conductive additive. 

PMID- 23855782
TI  - InBr3-mediated one-pot synthesis of 2-(polyhydroxylatedalkyl)-N-aryl-/
      alkylpyrroles from 1,2-cyclopropa-3-pyranone and amines.
AB  - An efficient one-pot synthesis of polyhydroxyalkyl-substituted pyrroles from 1,2
      cyclopropa-3-pyranones with primary amines is reported. With 10% of InBr3 as the
      catalyst, both aryl- and alkylamines as well as various 1,2-cyclopropa-3
      pyranones are well tolerated. This method is highly appealing because of its one
      pot process, mild reaction conditions, substrate simplicity, and broad substrate
      scope. 

PMID- 23855783
TI  - Lifestyle factors including less cutaneous sun exposure contribute to starkly
      lower vitamin D levels in U.K. South Asians compared with the white population.
AB  - BACKGROUND: Long-standing concerns over the vitamin D status of South Asian
      adults in the U.K. require studies using statistically valid sample sizes to
      measure annual variation and contributory lifestyle factors. OBJECTIVES: To
      measure annual variation in the vitamin D status of U.K. South Asians, to
      determine the associated lifestyle influences, and to compare these with a
      similar study of white adults. METHODS: A single-centre, prospective cohort study
      measuring circulating 25-hydroxyvitamin D [25(OH)D], sunlight exposure levels and
      lifestyle factors for 1 year in 125 ambulant South Asian adults with sun-reactive
      skin type V, aged 20-60 years, in Greater Manchester, U.K. (53.5 degrees N).
      RESULTS: The 25(OH)D levels of South Asians were alarmingly low. In summer, their
      median 25(OH)D level was 9.0 ng mL(-1) , [interquartile range (IQR) 6.7-13.1],
      falling to 5.8 ng mL(-1) (IQR 4.0-8.1) in winter. This compared with values in
      the white population of 26.2 ng mL(-1) (IQR 19.9-31.5) in summer and 18.9 ng mL(
      1) IQR (11.6-23.7) in winter. Median daily dietary vitamin D was lower in South
      Asians (1.32 MUg vs. 3.26 MUg for white subjects) and was compounded by low
      supplement use. Despite similar times spent outdoors, ultraviolet (UV) dosimeters
      recorded lower personal UV exposure among South Asians, indicating sun avoidance
      when outside, while sun exposure diaries recorded lower amounts of skin surface
      exposure. CONCLUSIONS: The majority of South Asians never reached sufficiency in
      vitamin D status. Lifestyle differences, with lower oral intake, sun exposure and
      rates of cutaneous production due to darker skin, indicate that standard advice
      on obtaining sufficient vitamin D needs modification for the South Asian
      community in the U.K.

PMID- 23855784
TI  - Use of bovine carpal joints as a training model for cruciate ligament repair.
AB  - BACKGROUND: Currently, there is a lack of cheap and effective training models to
      allow orthopaedic surgery trainees to learn the basics of anterior cruciate
      ligament reconstruction. The aim of this paper was to investigate the viability
      of using various animal joints as models for the training of anterior cruciate
      ligament reconstruction. METHOD: Equine stifles, bovine stifles and carpal
      joints, sheep stifles and porcine stifles, were sourced from a local abattoir.
      Each joint was assessed for the following criteria: suitable tendons for
      harvesting, ease of arthroscopy access, adequacy of arthroscopy view and suitable
      joint surfaces. Tendon harvesting, preparation, joint arthroscopy and tendon
      tunnelling were performed on the most suitable joint. RESULTS: Equine, bovine,
      sheep and porcine stifles were found to be unsuitable. The bovine carpal joint
      was similar to a human wrist joint with two rows of carpal bones and fused
      metacarpal bones, but with deeper flexion - similar to a human knee joint. The
      distal joint space was found to provide a greater range of flexion and space than
      the narrower proximal joint space. The joint capsule provided sufficient
      integrity during saline irrigation to allow adequate visualization of joint
      structures. Tendons surrounding the joint were found to be of similar diameter to
      human hamstring tendons and easily accessible. Tendon tunnelling was successfully
      performed in a manner similar to human anterior cruciate ligament repair.
      CONCLUSION: The use of bovine carpal joints is a cost-effective, safe and easily
      reproducible model for education on basic anterior cruciate ligament repair
      skills and technique prior to patient contact.

PMID- 23855785
TI  - HER2 and EGFR gene copy number alterations are predominant in high-grade salivary
      mucoepidermoid carcinoma irrespective of MAML2 fusion status.
AB  - AIMS: In this study, we aimed to investigate the molecular mechanisms underlying
      the development of mucoepidermoid carcinoma (MEC). METHODS AND RESULTS: In 31
      cases, we examined the MAML2 fusion status using reverse transcriptase-polymerase
      chain reaction, and HER2 and EGFR status using immunohistochemistry and
      chromogenic in-situ hybridization. MAML2 fusions were detected in 15 (57.7%) of
      26 MECs analysed, including 11 of 16 (68.8%) low-grade, two of four (50%)
      intermediate-grade and two of six (33.3%) high-grade MECs. HER2 gene
      amplification and an increased EGFR gene copy number (with balanced chromosome 7
      high-polysomy) were each detected in four of 28 (14.3%) MECs analysed.
      Irrespective of MAML2 fusion status, all seven high-grade MECs had an increased
      gene copy number of either HER2 or EGFR, in a mutually exclusive manner, whereas
      such abnormalities were extremely rare in low- and intermediate-grade MEC.
      CONCLUSIONS: These results suggest that HER2 or EGFR gene abnormality could play
      an important role in the development of high-grade MEC, and also in the
      progression from MAML2 fusion-positive low-/intermediate-grade to high-grade in a
      subset of MEC. Furthermore, we suggest that high-grade MEC comprises a
      heterogeneous group of tumours in terms of molecular pathogenesis, in particular
      MAML2 fusion status.

PMID- 23855786
TI  - Causes and consequences of intra- and inter-host heterogeneity in defence against
      nematodes.
AB  - Despite strong natural and artificial selection for increased resistance to
      nematode parasites, there is considerable heterogeneity between hosts in human,
      livestock and wildlife populations, with a minority of hosts carrying the
      majority of parasites. In addition, levels of defence may vary across the
      lifespan of individuals due to changes in their physiological state and infection
      history. Such variation influences nematode transmission dynamics and the
      evolution of parasite life-history strategies. Therefore, identifying sources of
      between- and within-individual variation in resistance and predicting their
      consequences is crucial for understanding the epidemiology of nematode parasitic
      diseases. In this review, several key sources of variation are identified, using
      examples from mouse models, immuno-epidemiological studies of human populations
      and observational and experimental studies of wildlife and livestock. The mutual
      applicability of approaches used across these study systems is emphasized, with
      the assertion that the concerted efforts of researchers from a range of
      disciplines will enable us to better understand the proximate and ultimate causes
      of variation in defence against nematode parasites. This will facilitate
      predictions of the epidemiological and evolutionary consequences of this
      variation, with the potential to improve disease treatment and management.

PMID- 23855787
TI  - Development of dimethyl sulfoxide solubility models using 163,000 molecules:
      using a domain applicability metric to select more reliable predictions.
AB  - The dimethyl sulfoxide (DMSO) solubility data from Enamine and two UCB pharma
      compound collections were analyzed using 8 different machine learning methods and
      12 descriptor sets. The analyzed data sets were highly imbalanced with 1.7-5.8%
      nonsoluble compounds. The libraries' enrichment by soluble molecules from the set
      of 10% of the most reliable predictions was used to compare prediction
      performances of the methods. The highest accuracies were calculated using a C4.5
      decision classification tree, random forest, and associative neural networks. The
      performances of the methods developed were estimated on individual data sets and
      their combinations. The developed models provided on average a 2-fold decrease of
      the number of nonsoluble compounds amid all compounds predicted as soluble in
      DMSO. However, a 4-9-fold enrichment was observed if only 10% of the most
      reliable predictions were considered. The structural features influencing
      compounds to be soluble or nonsoluble in DMSO were also determined. The best
      models developed with the publicly available Enamine data set are freely
      available online at http://ochem.eu/article/33409 . 

PMID- 23855788
TI  - Anorexia to obesity: problems for now and the future.

PMID- 23855789
TI  - HIV neuropathy pain continues to pose a challenge.

PMID- 23855790
TI  - A call to action and evolution.

PMID- 23855791
TI  - Peripheral neuropathy induces cutaneous hypersensitivity in chronically
      spinalized rats.
AB  - BACKGROUND/OBJECTIVES: The present study was aimed at the issue of whether
      peripheral nerve injury-induced chronic pain is maintained by supraspinal
      structures governing descending facilitation to the spinal dorsal horn, or
      whether altered peripheral nociceptive mechanisms sustain central
      hyperexcitability and, in turn, neuropathic pain. We examined this question by
      determining the contribution of peripheral/spinal mechanisms, isolated from
      supraspinal influence(s), in cutaneous hypersensitivity in an animal model of
      peripheral neuropathy. METHODS: Adult rats were spinalized at T8-T9; 8 days
      later, peripheral neuropathy was induced by implanting a 2-mm polyethylene cuff
      around the left sciatic nerve. Hind paw withdrawal responses to mechanical or
      thermal plantar stimulation were evaluated using von Frey filaments or a heat
      lamp, respectively. RESULTS: Spinalized rats without cuff implantation exhibited
      a moderate decrease in mechanical withdrawal threshold on ~day 10 (P < 0.05) and
      in thermal withdrawal threshold on ~day 18 (P < 0.05). However, cuff-implanted
      spinalized rats developed a more rapid and significant decrease in mechanical
      (~day 4; P < 0.001) and thermal (~day 10; P < 0.05) withdrawal thresholds that
      remained significantly decreased through the duration of the study. CONCLUSIONS:
      Our findings demonstrate an aberrant peripheral/spinal mechanism that induces and
      maintains thermal and to a greater degree tactile cutaneous hypersensitivity in
      the cuff model of neuropathic pain, and raise the prospect that altered
      peripheral/spinal nociceptive mechanisms in humans with peripheral neuropathy may
      have a pathologically relevant role in both inducing and sustaining neuropathic
      pain.

PMID- 23855792
TI  - Drugs in clinical development for multiple sclerosis: focusing on anti-CD20
      antibodies.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the
      central nervous system (CNS), traditionally considered to be an autoimmune
      disease. Despite the standard of care for patients with MS is significantly
      improved in recent years, there is still room for improvement in terms of
      effectiveness and also compliance. AREAS COVERED: The continuous improvements of
      our understanding of the pathophysiological changes that occur in MS have
      translated into many novel therapeutic agents at different stages of development.
      A number of therapies for MS are in advanced development and likely to be
      available soon. Along with these, we have also seen the appearance of a group of
      drugs considered together as a consequence of their similar design: the
      monoclonal antibodies (mAbs). Here, the focus will be on reviewing results that
      have emerged from a better clarification of MS pathogenesis to clinical trials of
      different anti-CD20 mAbs. EXPERT OPINION: The decision to switch established
      patients from well-known drugs to either new formulations or new agents will be
      made on balancing efficacy and tolerability of the existing treatments. Safety
      seems increasingly likely to become a key factor.

PMID- 23855793
TI  - Medication counselling: physicians' perspective.
AB  - Medication reviews have the potential to lower the incidence of prescribing
      errors. To benefit from a medication review, the prescriber must adhere to
      medication counselling. Adherence rates vary from 39 to 100%. The aim of this
      study was to examine counselling-naive hospital physicians' perspectives and
      demands to medication counselling as well as study factors that might increase
      adherence to the counselling. The study was conducted as a questionnaire survey
      among physicians at Aarhus University Hospital, Denmark. The questionnaire was
      developed based on focus group interviews and literature search, and was pilot
      tested among 30 physicians before being sent to 669 physicians. The questionnaire
      consisted of 35 items divided into four categories: attitudes (19 items),
      behaviours (3 items), assessment (8 items) and demographics (5 items). The
      response rate was 60% (400/669). Respondents were employed at psychiatric,
      medical or surgical departments. Eighty-five per cent of respondents agreed that
      patients would benefit of an extra medication review, and 72% agreed that there
      was a need for external medication counselling. The most important factor that
      could increase adherence was the clinical relevance of the counselling as 78%
      rated it of major importance. The most favoured method for receiving counselling
      was via the electronic patient record. 

PMID- 23855795
TI  - Toll-like receptor system and endometriosis.
AB  - Endometriosis is an estrogen-dependent chronic inflammatory condition associated
      with variable degrees of pelvic pain and infertility. Studies have showed that
      the growth and progression of endometriosis continue even in ovariectomized
      animals. This indicates that besides ovarian steroid hormones, the growth of
      endometriosis can be regulated by the innate immune system in the pelvic
      environment. As a component of innate immune system, increased infiltration of
      macrophages has been described in the intact tissue and peritoneal fluid of women
      with endometriosis. Different immune cells and dendritic cells express Toll-like
      receptors (TLR) and exhibit functional activity in response to microbial
      products. In this review article, we discuss the role of the TLR system in
      endometrium and endometriosis and outline the involvement of cytokines/endotoxin
      in causing adverse reproductive outcome. In the first part of this review
      article, the fundamentals of innate immune system, functional characteristics of
      TLR and signaling pathways of TLR4 are discussed for easy understanding by the
      readers. 

PMID- 23855796
TI  - Improvement of mucocutaneous involvement of immunoglobulin light chain
      amyloidosis after chemotherapy and hematopoietic stem cell transplantation for
      multiple myeloma.

PMID- 23855797
TI  - Hydrocarbon divergence and reproductive isolation in Timema stick insects.
AB  - BACKGROUND: Individuals commonly prefer certain trait values over others when
      choosing their mates. If such preferences diverge between populations, they can
      generate behavioral reproductive isolation and thereby contribute to speciation.
      Reproductive isolation in insects often involves chemical communication, and
      cuticular hydrocarbons, in particular, serve as mate recognition signals in many
      species. We combined data on female cuticular hydrocarbons, interspecific mating
      propensity, and phylogenetics to evaluate the role of cuticular hydrocarbons in
      diversification of Timema walking-sticks. RESULTS: Hydrocarbon profiles differed
      substantially among the nine analyzed species, as well as between partially
      reproductively-isolated T. cristinae populations adapted to different host
      plants. In no-choice trials, mating was more likely between species with similar
      than divergent hydrocarbon profiles, even after correcting for genetic
      divergences. The macroevolution of hydrocarbon profiles, along a Timema species
      phylogeny, fits best with a punctuated model of phenotypic change concentrated
      around speciation events, consistent with change driven by selection during the
      evolution of reproductive isolation. CONCLUSION: Altogether, our data indicate
      that cuticular hydrocarbon profiles vary among Timema species and populations,
      and that most evolutionary change in hydrocarbon profiles occurs in association
      with speciation events. Similarities in hydrocarbon profiles between species are
      correlated with interspecific mating propensities, suggesting a role for
      cuticular hydrocarbon profiles in mate choice and speciation in the genus Timema.

PMID- 23855798
TI  - Dioxin and estrogen signaling in lung adenocarcinoma cells with different aryl
      hydrocarbon receptor/estrogen receptor alpha phenotypes.
AB  - Evidence suggests that estrogen affects the pulmonary response to carcinogenic
      pollutants, such as dioxins. In this study, we examined dioxin and estrogen
      signaling cross-talk in lung adenocarcinoma cell lines that were engineered to
      exhibit different aryl hydrocarbon receptor (AhR)/estrogen receptor (ER) alpha
      phenotypes. Data showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) weakly
      antagonized estrogen-activated ERalpha activity in cells expressing abundant
      ERalpha, but little AhR. Increase of AhR expression or presence of a dioxin
      responsive element in proximity silenced the antiestrogenic effect of TCDD. AhR
      was bound to dioxin-responsive element and transcriptionally active in both TCDD
      untreated and -treated lung adenocarcinoma cells. 17beta-estradiol (E2) reduced
      basal and TCDD-induced AhR activity only in ERalpha-positive cells. AhR and
      ERalpha exhibited a protein-protein interaction in the presence of E2.
      Cotreatment with TCDD moderated this protein interaction. Colocalization of
      ERalpha and AhR at the estrogen-responsive site under E2 and TCDD/E2 treatments
      implied that E2 ? ERalpha might hijack AhR away from the dioxin-responsive site.
      Increasing the relative expression of AhR to ERalpha counteracted inhibition of
      AhR activity by E2 ? ERalpha. When AhR and ERalpha were both highly expressed,
      TCDD and E2 up-regulated expression of dual-responsive genes cytochrome P450
      (CYP) 1A1 and CYP1B1 in a cumulative manner, increasing the danger of metabolic
      activation of carcinogens. Whereas TCDD ? AhR and E2 ? ERalpha appeared to
      regulate CYP1B1 separately through their binding sites, E2 ? ERalpha increased
      the TCDD responsiveness and mRNA expression of CYP1A1 in a noncanonical way. In
      conclusion, AhR/ERalpha expression pattern, estrogen level, and promoter context
      determine the genomic action of dioxin in lung adenocarcinoma cells. 

PMID- 23855799
TI  - Efficient plasma route to nanostructure materials: case study on the use of m-WO3
      for solar water splitting.
AB  - One of the main challenges in developing highly efficient nanostructured
      photoelectrodes is to achieve good control over the desired morphology and good
      electrical conductivity. We present an efficient plasma-processing technique to
      form porous structures in tungsten substrates. After an optimized two-step
      annealling procedure, the mesoporous tungsten transforms into photoactive
      monoclinic WO3. The excellent control over the feature size and good contact
      between the crystallites obtained with the plasma technique offers an exciting
      new synthesis route for nanostructured materials for use in processes such as
      solar water splitting. 

PMID- 23855800
TI  - Complex phenological changes and their consequences in the breeding success of a
      migratory bird, the white stork Ciconia ciconia.
AB  - 1. The timing of bird migration has shifted in response to climate change.
      However, few studies have linked the potential consequences of any phenological
      shift on individual fitness and even fewer have disentangled the role of
      plasticity and microevolution in the observed shifts. 2. The arrival date and
      breeding success of white storks (Ciconia ciconia) have been recorded since the
      1880 s in Slovakia. We used data for two periods (1895-1913 and 1977-2007), which
      were considered, respectively, as populations before and after the start of
      climate warming. About 4000 male and 2500 female arrival dates along with 3000
      breeding attempts were studied. 3. Mean arrival dates did not differ between the
      two periods. During 1977-2007, males tended towards a slight delay for most
      fractions of arrival distribution. Protandry was reduced by 30% (1.44 days). 4.
      In both sexes, the early percentiles of the arrival distribution arrived later
      those years with warmer temperatures at the African wintering grounds, while late
      percentiles advanced their arrival when temperatures were higher in the European
      areas flown over during migration. 5. Mean breeding success of the Slovakian
      population has not changed since 1977. However, fecundity selection for arrival
      date reduced over the years: at the end of 1970s and 1980s, early breeders had
      more success than late breeders, but this seasonal trend disappeared towards the
      end of the study period. An early arrival and territory acquisition may have
      become less of an advantage due to the enhancement of feeding opportunities
      during the breeding season in recent decades. 6. A century ago, stork arrival
      varied spatially, with earlier arrivals at low altitudes, southern slopes and
      warmer and drier regions. This spatial variation mostly vanished, and at present,
      we found little correlations with topographical and climatic gradients. 7. We
      showed that long-term temporal changes in the timing of biological events may be
      complex because each fraction of a population and sex may show different temporal
      trends in their arrival dates. In addition, the effect of biotic and abiotic
      factors may change consistently in space and time, and thereby phenotypes' value
      depends on the circumstances that are expressed due to its variable fitness
      consequences.

PMID- 23855801
TI  - Interfacial entropy of water on rigid hydrophobic surfaces.
AB  - A simple theoretical model is proposed for computing the interfacial entropy of
      water at rigid hydrophobic surfaces. The interfacial entropy, which is not
      considered in mean field models of static wettability, is evaluated from the
      fluctuations of the water-surface dispersion energy at the single particle level
      and represents the configurational bias imposed on the fluid molecules by the
      attractive external potential of a solid wall. A comparison with results obtained
      from molecular dynamics simulations shows that the model quantitatively describes
      the entropy loss of water when a water-vapor interface turns to water in contact
      with hydrophobic surfaces such as graphene, graphite, and diamond, while it
      overestimates this quantity on hydrophilic surfaces. 

PMID- 23855803
TI  - Effect of Aegle marmelos leaf extract on N-methyl N-nitrosourea-induced
      hepatocarcinogensis in Balb/c mice.
AB  - CONTEXT AND OBJECTIVE: Tobacco smoke and nitrostable foods containing N-methyl N
      nitrosourea (MNU) are among the primary causes of liver cancer. To substantiate
      the beneficial claims ascribed to Aegle marmelos (L.) Correa (Rutaceae), the
      hepatoprotective potential of its leaf extract was studied using an MNU-induced
      hepatocarcinogenesis model in Balb/c mice. MATERIALS AND METHODS: After dose
      selection, 40 mice were randomly assigned to 4 groups: I (control), II
      (intraperitoneally (i.p.) primed with 50 mg/kg MNU), III (100 mg/kg A. marmelos
      hydroalcoholic extract (HEAM) i.p.) and IV (MNU + HEAM, i.p.). Inflammatory (IL
      1beta, IL-6), anti-inflammatory (IL-4) cytokine expression, apoptosis (Bcl-2) and
      tumor-related (p53, c-jun) genes were assessed at mRNA level. HEAM effects on
      hematological parameters were examined. RESULTS AND DISCUSSION: HEAM treatment
      decreased IL-1beta, IL-6, Bcl-2 and c-jun respectively expressions by 90, 25, 53
      and 30%, respectively. p53 and IL-4 expression was up-regulated by 1.5- and 2
      fold. MNU decreased hemoglobin concentration (25%), lymphocyte count (42%) and
      increased leukocyte (100%), platelet (4-fold), neutrophil (43%), monocyte (10
      fold) and eosinophil (10-fold) counts in Group II mice while HEAM modulated the
      same parameters by -7%, -21%, +24%, +3-fold, +12%, +3-fold and +4-fold,
      respectively, in MNU-induced mice compared to control. HEAM protective effect was
      confirmed by Raman spectroscopy where the MNU-induced peak at 1252 cm(-1) was
      normalized. DNA fragmentation data suggest apoptosis as one of the protective
      mechanisms of HEAM. CONCLUSION: The hepatoprotective, anti-carcinogenic and
      immunomodulatory effects of A. marmelos extract indicate potential beneficial
      effects in cancer therapy.

PMID- 23855804
TI  - Differentiation of irradiation and cetuximab induced skin reactions in patients
      with locally advanced head and neck cancer undergoing radioimmunotherapy: the
      HICARE protocol (head and neck cancer: immunochemo and radiotherapy with erbitux)
      - a multicenter phase IV trial.
AB  - BACKGROUND: In order to improve the clinical outcome of patients with locally
      advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable
      to receive platinum-based chemoradiation, radiotherapy can be intensified by
      addition of cetuximab, a monoclonal antibody that blocks the epidermal growth
      factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible
      treatment option showing a favourable toxicity profile. The most frequent side
      effect of radiotherapy is radiation dermatitis, the most common side effect of
      treatment with cetuximab is acneiform rash. Incidence and severity of these
      frequent, often overlapping and sometimes limiting skin reactions, however, are
      not well explored. A clinical and molecular differentiation between radiogenic
      skin reactions and skin reactions caused by cetuximab which may correlate with
      outcome, have never been described before. METHODS/DESIGN: The HICARE study is a
      national, multicenter, prospective phase IV study exploring the different types
      of skin reactions that occur in patients with LASCCHN undergoing
      radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with
      LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint
      is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02).
      Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be
      administered as loading dose and then weekly during the radiotherapy. Irradiation
      will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional
      radiation therapy. DISCUSSION: The HICARE trial is expected to be one of the
      largest trials ever conducted in head and neck cancer patients. The goal of the
      HICARE trial is to differentiate skin reactions caused by radiation from those
      caused by the monoclonal antibody cetuximab, to evaluate the incidence and
      severity of these skin reactions and to correlate them with outcome parameters.
      Besides, the translational research program will help to identify and confirm
      novel peripheral blood based molecular predictors and surrogates for treatment
      response and resistance. TRIAL REGISTRATION: Clinical Trial Identifier,
      NCT01553032 (clinicaltrials.gov)EudraCT number: 2010-019748-38.

PMID- 23855805
TI  - The genetics of infectious disease susceptibility: has the evidence for epistasis
      been overestimated?
AB  - Interactions amongst genes, known as epistasis, are assumed to make a substantial
      contribution to the genetic variation in infectious disease susceptibility, but
      this claim is controversial. Here, we focus on the debate surrounding the
      evolutionary importance of interactions between resistance loci and argue that
      its role in explaining overall variance in disease outcomes may have been
      overestimated. 

PMID- 23855806
TI  - Solution thermodynamic stability of complexes formed with the octadentate
      hydroxypyridinonate ligand 3,4,3-LI(1,2-HOPO): a critical feature for efficient
      chelation of lanthanide(IV) and actinide(IV) ions.
AB  - The solution thermodynamics of water-soluble complexes formed between Ce(III),
      Ce(IV), Th(IV) and the octadentate chelating agent 3,4,3-LI(1,2-HOPO) were
      investigated. Several techniques including spectrofluorimetric and automated
      spectrophotometric titrations were used to overcome the slow spontaneous
      oxidation of Ce(III) complexes yielding to stability constants of log beta110 =
      17.4 +/- 0.5, log beta11-1 = 8.3 +/- 0.4 and log beta111 = 21.2 +/- 0.4 for
      [Ce(III)(3,4,3-LI(1,2-HOPO))](-), [Ce(III)(3,4,3-LI(1,2-HOPO)(OH)](2-), and
      [Ce(III)(3,4,3-LI(1,2-HOPO)H], respectively. Using the spectral properties of the
      hydroxypyridinonate chelator in ligand competition titrations against
      nitrilotriacetic acid, the stability constant log beta110 = 41.5 +/- 0.5 was
      determined for [Ce(IV)(3,4,3-LI(1,2-HOPO))]. Finally, the extraordinarily stable
      complex [Ce(IV)(3,4,3-LI(1,2-HOPO))] was used in Th(IV) competition titrations,
      resulting in a stability constant of log beta110 = 40.1 +/- 0.5 for [Th(IV)3,4,3
      LI(1,2-HOPO))]. These experimental values are in excellent agreement with
      previous estimates, they are discussed with respect to the ionic radius and
      oxidation state of each cationic metal, and allow predictions on the stability of
      other actinide complexes including [U(IV)(3,4,3-LI(1,2-HOPO))], [Np(IV)(3,4,3
      LI(1,2-HOPO))], and [Pu(IV)(3,4,3-LI(1,2-HOPO))]. Comparisons with the standard
      ligand diethylenetriamine pentaacetic acid (DTPA) provide a thermodynamic basis
      for the observed significantly higher efficacy of 3,4,3-LI(1,2-HOPO) as an in
      vivo actinide decorporation agent. 

PMID- 23855808
TI  - High specific and ultrasensitive isothermal detection of microRNA by padlock
      probe-based exponential rolling circle amplification.
AB  - In this paper, a padlock probe-based exponential rolling circle amplification (P
      ERCA) assay is developed for highly specific and sensitive detection of microRNA
      (miRNA). The padlock probe is composed of a hybridization sequence to miRNA and a
      nicking site for nicking endonuclease. Using the miRNA as a template, specific
      ligation to the padlock probe and linear rolling circle reaction (LRCA) are
      achieved under isothermal conditions. After multiple nicking reactions, many
      copies of short DNA products are successively produced and then used as triggers
      in next circle amplification. Thus, a small amount of miRNAs are converted to a
      large number of triggers to initiate the rolling circle amplification reaction,
      and circular exponential signal amplification is achieved. This padlock probe
      based exponential rolling circle amplification assay exhibits a remarkable
      sensitivity of 0.24 zmol using optimized sequences of the padlock probe. The
      target-dependent circularization of the padlock probe and the ligation reaction
      could improve the specificity effectively, leading to single-nucleotide
      difference discrimination between miRNA family members. The miRNA analysis in
      human lung cells was performed with this method. The result indicates this highly
      sensitive P-ERCA strategy will become a promising miRNA quantification method in
      early clinical diagnostics. 

PMID- 23855807
TI  - Molecular epidemiology of Plasmodium vivax in Latin America: polymorphism and
      evolutionary relationships of the circumsporozoite gene.
AB  - BACKGROUND: The origins and dispersal of Plasmodium vivax to its current
      worldwide distribution remains controversial. Although progress on P. vivax
      genetics and genomics has been achieved worldwide, information concerning New
      World parasites remains fragmented and largely incomplete. More information on
      the genetic diversity in Latin America (LA) is needed to better explain current
      patterns of parasite dispersion and evolution. METHODS: Plasmodium vivax
      circumsporozoite protein gene polymorphism was investigated using polymerase
      chain reaction amplification and restriction fragment length polymorphism (PCR
      RFLP), and Sanger sequencing in isolates from the Pacific Ocean coast of Mexico,
      Nicaragua, and Peru. In conjunction with worldwide sequences retrieved from the
      Genbank, mismatch distribution analysis of central repeat region (CRR), frequency
      estimation of unique repeat types and phylogenetic analysis of the 3' terminal
      region, were performed to obtain an integrative view of the genetic relationships
      between regional and worldwide isolates. RESULTS: Four RFLP subtypes, vk210a, b,
      c and d were identified in Southern Mexico and three subtypes vk210a, e and f in
      Nicaragua. The nucleotide sequences showed that Mexican vk210a and all Nicaraguan
      isolates were similar to other American parasites. In contrast, vk210b, c and d
      were less frequent, had a domain ANKKAEDA in their carboxyl end and clustered
      with Asian isolates. All vk247 isolates from Mexico and Peru had identical RFLP
      pattern. Their nucleotide sequences showed two copies of GGQAAGGNAANKKAGDAGA at
      the carboxyl end. Differences in mismatch distribution parameters of the CRR
      separate vk247 from most vk210 isolates. While vk247 isolates display a
      homogeneous pattern with no geographical clustering, vk210 isolates display a
      heterogeneous geographically clustered pattern which clearly separates LA from
      non-American isolates, except vk210b, c and d from Southern Mexico. CONCLUSIONS:
      The presence of vk210a in Mexico and vk210e, f and g in Nicaragua are consistent
      with other previously reported LA isolates and reflect their circulation
      throughout the continent. The vk210b, c and d are novel genotypes in LA. Their
      genetic relationships and low variability within these vk210 and/or within the
      vk247 parasites in Southern Mexico suggest its recent introduction and/or recent
      expansion to this region. The global analysis of P. vivax csp suggests this
      parasite introduction to the region and likely LA by different independent
      events.

PMID- 23855809
TI  - Synthesis and asymmetric resolution of alpha-azido-peroxides.
AB  - An unprecedented synthesis of alpha-azido-peroxides has been developed using an
      FeCl3-catalyst starting from carbonyl, TMS-azide, and hydroperoxide. Further, a
      base promoted decomposition of synthesized secondary alpha-azido-peroxides to
      provide the corresponding tert-butyl esters has been disclosed. Finally, an
      asymmetric kinetic resolution of such alpha-azido-peroxides has also been
      developed to provide chiral alpha-azido-peroxides in excellent enantiopurity. 

PMID- 23855810
TI  - Splanchnic vein thrombosis in myeloproliferative neoplasms.
AB  - Splanchnic vein thrombosis (SVT) is one of the most important complications of
      myeloproliferative neoplasms (MPN). Although MPN are common causes of SVT, the
      pathophysiological mechanisms underlying this predisposition, their epidemiology
      and natural history are not fully understood. Studies have concentrated on the
      generalized prothrombotic environment generated by MPN and their relationship
      with abnormal blood counts, thereby furthering our knowledge of arterial and
      venous thrombosis in this population. In contrast, there are few studies that
      have specifically addressed SVT in the context of MPN. Recent research has
      demonstrated in patients with MPN the existence of factors increasing the risk of
      SVT such as the presence of the JAK2 V617F mutation and its 46/1 haplotype.
      Features unique to the circulating blood cells, splanchnic vasculature and
      surrounding micro-environment in patients with MPN have been described. There are
      also abnormalities in local haemodynamics, haemostatic molecules, the spleen, and
      splanchnic endothelial and endothelial progenitor cells. This review considers
      these important advances and discusses the contribution of individual anomalies
      that lead to the development of SVT in both the pre-neoplastic and overt stage of
      MPN. Clinical issues relating to epidemiology, recurrence and survival in these
      patients have also been reviewed and their results discussed. 

PMID- 23855811
TI  - The importance of hydrogen bonding and aromatic stacking to the affinity and
      efficacy of cannabinoid receptor CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1
      [(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H
      pyrazole-3-carboxamide (SR144528).
AB  - Despite the therapeutic promise of the subnanomolar affinity cannabinoid CB2
      antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)
      1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528, 1),
      little is known about its binding site interactions and no primary interaction
      site for 1 at CB2 has been identified. We report here the results of Glide
      docking studies in our cannabinoid CB2 inactive state model that were then tested
      via compound synthesis, binding, and functional assays. Our results show that the
      amide functional group of 1 is critical to its CB2 affinity and efficacy and that
      aromatic stacking interactions in the TMH5/6 aromatic cluster of CB2 are also
      important. Molecular modifications that increased the positive electrostatic
      potential in the region between the fenchyl and aromatic rings led to more
      efficacious compounds. This result is consistent with the EC-3 loop negatively
      charged amino acid, D275 (identified via Glide docking studies) acting as the
      primary interaction site for 1 and its analogues. 

PMID- 23855813
TI  - MALDI imaging on large-scale tissue microarrays identifies molecular features
      associated with tumour phenotype in oesophageal cancer.
AB  - AIMS: Matrix-assisted laser desorption/ionisation mass spectrometry imaging
      (MALDI-MSI) and tissue microarray (TMA) technologies were jointly utilized to
      search for molecular features associated with clinicopathological parameters in
      oesophageal cancer. METHODS AND RESULTS: Two TMAs from formalin-fixed tissue
      samples, including 300 adenocarcinomas and 177 squamous cell carcinomas with
      clinical follow-up data, were analysed. MALDI-MSI analysis revealed 72 distinct
      mass per charge (m/z) signals associated with tumour cells, 48 of which were
      found in squamous cell carcinomas only, and 12 of which were specific for
      adenocarcinomas. In adenocarcinomas, six signals were linked to early-stage (pT1
      T2) tumours (two signals) and the presence (one signal) or absence (three
      signals) of lymph node metastasis. In squamous cell carcinomas, 24 signals were
      strongly linked to different phenotypic features, including tumour stage (four
      signals), histological grade (four signals), and lymph node metastasis (three
      signals). CONCLUSIONS: The high number of m/z signals that were found to be
      significantly linked to one or more phenotypic features of oesophageal cancer
      highlights the power of MALDI-MSI in the analysis of high-density TMAs. The data
      also emphasise substantial biological differences between adenocarcinomas and
      squamous cell carcinomas.

PMID- 23855812
TI  - Vascular trauma in Western Australia: a comparison of two study periods over 15
      years.
AB  - BACKGROUND: Royal Perth Hospital (RPH) has become Western Australia's only
      designated adult major trauma facility since a previous study of vascular trauma
      was conducted in 2001 at the same facility. The aim of this study is to identify
      changes in vascular trauma patterns over the two study periods and compare these
      changes with international literature. METHODS: All individuals presenting to RPH
      between January 2000 and December 2010 with vascular injury were identified from
      a prospective trauma database for this descriptive study. Injuries were
      classified using the Abbreviated Injury Score (AIS). RESULTS: The incidence of
      vascular trauma as a percentage of total trauma increased over the two study
      periods. The current 10-year study included 45 164 patients on the trauma
      database, of which 1205 patients (2.6%) sustained 1335 vascular injuries, an
      increase from 1% in the previous 5-year study at the same facility. Males aged 20
      29 years were more frequently injured. Blunt trauma occurred more frequently than
      penetrating. The extremities, particularly the upper limbs were most commonly
      injured. The most common causes of injury for each region were as follows;
      motorbike crash (MBC), motor vehicle crash (MVC) and stabbing (neck, thorax and
      abdomen), MBC and MVC (lower limb) and piercing injuries (upper limb). Injury
      Severity Score (ISS) and mortality 43% (32 of 75) were highest for thoracic
      injuries, particularly thoracic aorta injury. Mortality rate has decreased.
      CONCLUSION: Vascular injuries in Western Australia are increasing. MVC are the
      most common cause of life threatening injury. Road safety interventions targeting
      young males are likely to reduce trauma.

PMID- 23855814
TI  - Cyclopentannulation of conjugated enones using a vinyldiazomethane-based reagent.
AB  - Herein, we describe a two-step method for the cyclopentannulation of conjugated
      enones using methyl 3-(tert-butyldimethylsilyloxy)-2-diazo-3-butenoate (1) as a
      bifunctional reagent. The enol silane and stabilized diazoalkane functionalities
      are exploited independently in sequential Mukaiyama-Michael and
      diastereoselective alpha,alpha'-diketone coupling. Di-, tri-, and
      tetrasubstituted enones are amenable to annulation under this protocol. Overall,
      this chemistry is an effective surrogate for a substituted "acetone 1,3-dipole". 

PMID- 23855815
TI  - Postpartum symphysis pubis separation.

PMID- 23855816
TI  - Fentanyl buccal tablet compared with immediate-release oxycodone for the
      management of breakthrough pain in opioid-tolerant patients with chronic cancer
      and noncancer pain: a randomized, double-blind, crossover study followed by a 12
      week open-label phase to evaluate patient outcomes.
AB  - OBJECTIVE: Evaluate analgesic efficacy, functional benefit, and patient
      satisfaction with fentanyl buccal tablet vs immediate-release oxycodone for
      breakthrough pain (BTP). DESIGN: Randomized, double-blind, active-controlled
      crossover trial and 12-week open-label extension. SETTING: Forty-two U.S. sites.
      PATIENTS: Opioid-tolerant patients with predominantly chronic noncancer pain
      experiencing BTP. INTERVENTION: Patients were randomized to open-label titration
      periods with fentanyl buccal tablet followed by oxycodone or vice versa for BTP
      management. After titrating to a successful dose of both medications (single dose
      providing adequate analgesia without unacceptable adverse events), patients were
      re-randomized to treat 10 BTP episodes with one medication and 10 with the other.
      OUTCOME MEASURES: The primary efficacy measure was pain intensity (PI) difference
      15 minutes postdose. Secondary measures included PI difference 5, 10, 30, 45, and
      60 minutes postdose; sum of PI differences 30 and 60 minutes postdose; >=33% and
      >=50% reduction in PI; and pain relief. Questionnaires assessed functional
      status/satisfaction. RESULTS: Of 213 patients enrolled, 149 achieved a successful
      dose of both medications; 131 completed the double-blind phase and 112 the open
      label phase. PI difference at 15 minutes (mean [standard deviation]) was greater
      with fentanyl buccal tablet (0.88 [1.20]) vs oxycodone (0.76 [1.13]; P < 0.001).
      Patients preferred fentanyl buccal tablet (47%) over oxycodone (35%); 18% had no
      preference. Patients and clinicians reported consistently better functional
      improvement and satisfaction with fentanyl buccal tablet vs short-acting opioids
      (P < 0.05). CONCLUSIONS: Fentanyl buccal tablet was associated with rapid onset
      of analgesia and improvements in functional status and patient satisfaction
      compared with immediate-release oxycodone.

PMID- 23855817
TI  - New therapy options for amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing
      neurodegenerative disease leading almost irrevocably to paralysis and death
      within 5 years after the first symptoms. Since the approval of riluzole, all
      other therapeutic trials have been negative, including many that followed hopeful
      preclinical and early clinical data. New approaches are needed to uncover
      effective treatments for this still-devastating disease. AREAS COVERED: The
      review summarizes the current approaches to clinical drug development in ALS. It
      focuses on several new trials listed on PubMed Central or the National Institutes
      of Health online trial registry. New targets for therapeutic intervention in ALS
      include skeletal muscle, energetic metabolism and cell replacement. Two different
      approaches are directed at muscle: interventions that influence proteins near the
      neuromuscular junction such as Nogo-A; in contrast to drugs pointed toward
      disease physiology, therapies that directly increase strength. Other trials are
      evaluating nutritional interventions. Current cell therapy strategies utilize
      various types of stem cells to study disease pathophysiology, support neurons or
      surrounding cells through gene therapy or release of neurotrophic factors, or
      directly replace cells. The review includes a section on known genetic influences
      in ALS and future directions for the field. EXPERT OPINION: These new
      interventions have important implications for the direction of ALS research.
      Investigators are focusing less on physiological mechanisms inside the neuron, a
      process that has proved unfruitful for nearly two decades, and more on concepts
      that have not been examined previously. These studies will surely add to the
      overall understanding of ALS. Future research will test ways to reduce gene
      expression in those with known mutations, as well as means to reduce the spread
      of aggregated protein.

PMID- 23855818
TI  - Impact on L-carnitine Homeostasis of Short-term Treatment with the Pivalate
      Prodrug Tenofovir Dipivoxil.
AB  - Pivalate-generating prodrugs have been suggested to cause clinically significant
      hypocarnitinaemia. Tenofovir dipivoxil, a novel ester prodrug of tenofovir, can
      be used for treatment for hepatitis B and HIV infection and it was necessary to
      evaluate the effect of its treatment on carnitine homeostasis. We sought to
      investigate the effect of Class 1 drug tenofovir dipivoxil on endogenous L
      carnitine level during a 72-hr test in healthy Chinese volunteers and to
      establish a suitable dose of L-carnitine nutritional supplement for patients who
      were administered short-term tenofovir dipivoxil tablets for treatment for
      hepatitis B and herpes simplex virus infection. Tenofovir dipivoxil was
      administered in one of eight dosing regimens (single dose 150, 300 and 600 mg,
      multiple dose 300, 450, and 600 mg, multiple dose 450 (600) mg tenofovir
      dipivoxil and 0.5 g L-carnitine) to gender-balanced groups of 84 healthy Chinese
      volunteers. Plasma concentrations of L-carnitine were quantified before, during
      and after treatment. Plasma L-carnitine concentrations fell during tenofovir
      dipivoxil dosing. The nadir in L-carnitine concentration was dependent on the
      dose of tenofovir dipivoxil and it decreased from 6.1 +/- 0.6 to 4.4 +/- 0.8
      MUg/ml, 6.1 +/- 1.8 to 3.3 +/- 1.2 MUg/ml, 6.2 +/- 0.6 to 2.5 +/- 0.5 MUg/ml for
      single doses of 150, 300, 600 mg tenofovir dipivoxil tablets and from 6.0 +/- 1.4
      to 2.1 +/- 1.5 MUg/ml, 6.2 +/- 0.4 to 0.9 +/- 0.5 MUg/ml for multiple doses of
      450, 600 mg tenofovir dipivoxil tablets, respectively. Short-term administration
      of tenofovir dipivoxil results in hypocarnitinaemia and increased losses of
      carnitine in resulting of minor adverse events of decreased food appetite,
      nausea, abdominal distention and muscle weakness. 

PMID- 23855819
TI  - Perioperative haemostatic management of haemophilic mice using normal mouse
      plasma.
AB  - Intense haemostatic interventions are required to avoid bleeding complications
      when surgical procedures are performed on haemophilia patients. The objective of
      this study was to establish an appropriate protocol for perioperative haemostatic
      management of haemophilic mice. We assessed the prophylactic haemostatic effects
      of normal mouse plasma (NMP) on haemophilia B (HB) mice for both a skin flap
      procedure and a laparotomy. When 500 MUL of NMP was administered to the mice,
      plasma factor IX (FIX:C) levels peaked at 15.1% immediately after intravenous
      (IV) administration, at 6.1% 2 h after intraperitoneal (IP) administration and at
      2.7% 6 h after subcutaneous administration. Administering 500 MUL of NMP via IP
      or IV 30 min in advance enabled the skin flap procedure to be performed safely
      without any complications. After the laparotomy procedure, several mice in the IP
      administration group exhibited lethal bleeding, but all mice survived in the IV
      administration group. Anti-mouse FIX inhibitors did not develop, even after
      repetitive administrations of NMP. However, human FIX concentrates, especially
      plasma-derived concentrates, elicited the anti-human FIX inhibitors. The results
      show that administering 500 MUL of NMP via IV or IP 30 min in advance enables
      surgical procedures to be safely performed on HB mice, and that IV administration
      is more desirable than IP if the procedure requires opening of the abdominal
      wall.

PMID- 23855820
TI  - Iron oxide-induced thermal effects on solid-state upconversion emissions in
      NaYF4:Yb,Er nanocrystals.
AB  - Multifunctional materials exhibiting photon upconversion show promising
      applications for biological imaging and sensing. In this study, we examine the
      solid-state upconversion emission of NaYF4:Yb,Er nanoparticles in the presence of
      iron oxide nanoparticles. Fe3O4 nanoparticles (6 nm) were mixed with NaYF4:Yb,Er
      nanoparticles (either 10 or 50 nm) in varying proportions by drying chloroform
      solutions of nanoparticles onto glass slides. Upconversion spectra were acquired,
      and a laser power-dependent emission was observed and correlated with the iron
      oxide content in the mixture. Changes in the lattice temperature of the
      upconverting particles were monitored by careful observation of the relative
      intensities of the (2)H11/2 and (4)S3/2 ->( 4)I15/2 transitions. The emission
      characteristics observed are consistent with an iron oxide-induced thermal effect
      that is dependent on both the laser power and the proportion of iron oxide. The
      results highlight that the thermal effects of mixed nanoparticle systems should
      be considered in the design of luminescent upconverting hybrid materials. 

PMID- 23855821
TI  - Chiral self-assembly of designed amphiphiles: influences on aggregate morphology.
AB  - A series of novel amphiphiles were designed for self-assembly into chiral
      morphologies, the amphiphiles consisting of a glutamic acid (Glu) headgroup
      connected through an 11-carbon alkoxy chain to a diphenyldiazenyl (Azo) group and
      terminated with a variable length alkyl chain (R-Azo-11-Glu, where R denotes the
      number of carbons in the distal chain). TEM imaging of amphiphile aggregates self
      assembled from heated, methanolic, aqueous solution showed that chiral order,
      expressed as twisted ribbons, helical ribbons, and helically based nanotubes,
      increased progressively up to a distal chain length containing eight carbons, and
      then decreased with further increases in distal chain length. TEM and CD showed
      that the chiral aggregations of single enantiomers were influenced by the
      molecular chirality of the headgroup. However, the assembly of D,L-10-Azo-11-Glu
      into nanotubes demonstrated that chiral symmetry breaking effected by the azo
      group was also relevant to the chiral organization of the amphiphiles. The chiral
      order of aggregate morphologies was additionally affected by the temperature and
      solvent composition of assembly in a manner correlated to the mechanism driving
      assembly; i.e., D,L-10-Azo-11-Glu was sensitive to the temperature of assembly
      but less so to solvent composition, while L-14-Azo-11-Glu was sensitive to
      solvent composition and not to temperature. FTIR and UV-vis spectroscopic
      investigations into the organization of the head and azo groups, in chiral and
      achiral structures, illustrated that a balance of the influences of the
      hydrophilic and hydrophobic components on self-assembly was required for the
      optimization of the chiral organization of the self-assembled structures.

PMID- 23855822
TI  - Marine protected areas facilitate parasite populations among four fished host
      species of central Chile.
AB  - 1. Parasites comprise a substantial proportion of global biodiversity and exert
      important ecological influences on hosts, communities and ecosystems, but our
      knowledge of how parasite populations respond to human impacts is in its infancy.
      2. Here, we present the results of a natural experiment in which we used a system
      of highly successful marine protected areas and matched open-access areas in
      central Chile to assess the influence of fishing-driven biodiversity loss on
      parasites of exploited fish and invertebrate hosts. We measured the burden of
      gill parasites for two reef fishes (Cheilodactylus variegatus and Aplodactylus
      punctatus), trematode parasites for a keyhole limpet (Fissurella latimarginata),
      and pinnotherid pea crab parasites for a sea urchin (Loxechinus albus). We also
      measured host density for all four hosts. 3. We found that nearly all parasite
      species exhibited substantially greater density (# parasites m(-2)) in protected
      than in open-access areas, but only one parasite species (a gill monogenean of C.
      variegatus) was more abundant within hosts collected from protected relative to
      open-access areas. 4. These data indicate that fishing can drive declines in
      parasite abundance at the parasite population level by reducing the availability
      of habitat and resources for parasites, but less commonly affects the abundance
      of parasites at the infrapopulation level (within individual hosts). 5.
      Considering the substantial ecological role that many parasites play in marine
      communities, fishing and other human impacts could exert cryptic but important
      effects on marine community structure and ecosystem functioning via reductions in
      parasite abundance.

PMID- 23855824
TI  - Rapid transition of NESTIN-expressing dividing cells from PROP1-positive to PIT1
      positive advances prenatal pituitary development.
AB  - We recently reported that the quantitative and qualitative transition of
      stem/progenitor cells occurs by the acquisition of a novel mechanism in the
      terminal differentiation during postnatal development of the anterior pituitary.
      We hypothesised that this novel mechanism is an alteration of a cell supply
      system accompanying proliferation of the progenitor cells. In the present study,
      we examined the proliferation activities of progenitor cells by indication of the
      expression of Nestin, a marker of rapidly dividing progenitor cells, aiming to
      verify our hypothesis and to resolve another outstanding issue regarding whether
      the Nestin gene is expressed in the pituitary. We found that NESTIN-positive
      dividing cells certainly exist in the pituitary through all stages of
      development. Almost all of the PROP1-positive progenitor cells express Nestin in
      early embryonic pituitary development. Thereafter, Nestin-expressing dividing
      cells involved in the cell supply system transfer from PROP1-positive progenitor
      cells to committed progenitor cells, such as PIT1-positive cells, on neonatal
      pituitary development. Furthermore, our data, together with the findings of
      previous studies on cell lineage tracing analyses using Nestin-Cre mice derived
      by the central nervous system (CNS)-specific Nestin promoter, suggest that at
      least two regulation systems for Nestin-expression exist in the pituitary, with
      the majority of these not being CNS-specific. 

PMID- 23855823
TI  - Vitiligo after combination therapy of pegylated interferon-alpha-2a, ribavirin
      and vitamin D in a patient with chronic hepatitis C.

PMID- 23855825
TI  - Identification of novel modulators for ionotropic glutamate receptor, iGluA2 by
      in-silico screening.
AB  - BACKGROUND: Ionotropic glutamate receptors (iGluAs, IUPHAR nomenclature) are the
      major excitatory amino acid neurotransmitter receptors in the mammalian central
      nervous system (CNS). iGluAs are potential therapeutic drug targets for various
      neurological disorders including ischemia, epilepsy, Parkinson's and Alzheimer's
      diseases. The known iGluA modulators, cyclothiazide (CTZ), IDRA-21, and other
      benzothiadiazide derivatives (ALTZ, HCTZ, and CLTZ) bind to the ligand-binding
      domain of flip-form of iGluA2 at the dimer interface, thereby increasing steady
      state activation by reducing desensitization. METHODS: To discover new modulator
      compounds, we performed virtual screening for the ligand binding domain (LBD) of
      iGluA2 against NCI Diversity Set III library containing 1597 compounds, and
      subsequently performed binding-energy analysis for selected compounds. The
      crystal structure of rat iGluA2 S1S2J (PDB ID: 3IJO) was used for docking
      studies. RESULTS AND CONCLUSION: From this study, we obtained four compounds: (1)
      10-2(methoxyethyl)-3-phenylbenzo[g]pteridine-2,4-dione, (2) 2
      benzo[e]benzotriazol-2-yl-aniline, (3) 9-nitro-6H-indolo-(2,3,-b)quinoxaline, and
      (4) 1-hydroxy-n-(3-nitrophenyl)-2-napthamide. The binding mode of these four
      compounds is very similar to that of abovementioned established modulators: two
      molecules of each compound independently bind to the protein symmetrically at the
      dimer interface; occupy the subsites B, C, B' and C'; potentially interact with
      Ser518 and Ser775. Binding energy analysis shows that all the four hits are
      comparable to the drug molecule, CTZ, and hence, we propose that the discovered
      hits may be potential molecules to develop new chemical libraries for modulating
      the flip form of iGluA2 function.

PMID- 23855826
TI  - Leptin attenuates lipopolysaccharide or oleic acid-induced acute lung injury in
      mice.
AB  - Leptin is reported to be involved in acute lung injury (ALI). However, the role
      and underlying mechanisms of leptin in ALI remain unclear. The aim of this study
      was to determine whether leptin deficiency promoted the development of ALI. LPS
      or oleic acid (OA) were administered to wild-type and leptin deficient (ob/ob)
      mice to induce ALI. Leptin level, survival rate, and lung injury were examined.
      Results showed that leptin levels were predominantly increased in the lung, but
      also in the heart, liver, kidney, and adipose tissue after LPS adminiatration.
      Compared with wild-type mice, LPS- or OA-induced lung injury was worse and the
      survival rate was lower in ob/ob mice. Moreover, leptin deficiency promoted the
      release of proinflammatory cytokines. Exogenous administration of leptin reduced
      lethality in ob/ob mice and ameliorated lung injury partly through inhibiting the
      activation of NF-kappaB, p38, and ERK pathways. These results indicated that
      leptin deficiency contributed to the development of lung injury by enhancing
      inflammatory response, and a high level of leptin improved survival and protected
      against ALI. 

PMID- 23855828
TI  - Objectively assessed physical activity is associated with increased hair cortisol
      content in young adults.
AB  - Assessing long-term cortisol secretion presents difficulties when cortisol
      measurement is carried out by saliva, plasma and urine analyses. Hair cortisol
      has gained increased interest as an alternative biological marker. So far, one
      study has been published studying hair cortisol in endurance athletes, showing
      higher levels compared to controls. Using accelerometer data in the present
      study, we cross-sectionally explored the relationship between moderate physical
      activity (MPA) and vigorous physical activity (VPA) levels and hair cortisol
      concentrations after taking into account age, gender, and perceived stress. Hair
      specimens were collected from 46 university students (20 males, 26 females, Mage
      +/- SD =21.2 +/- 1.87 years). Participants provided information about their socio
      demographic background and levels of perceived stress. Accelerometer data were
      collected to assess physical activity. Cortisol concentrations were measured in
      the first 3-cm hair segment nearest to the scalp. MPA was not correlated with
      hair cortisol content (r = -0.08). A significant correlation was found between
      VPA and hair cortisol (r = 0.34, p < 0.05). A regression analysis revealed that
      participants with higher VPA had elevated hair cortisol concentrations even after
      taking into account age, gender and perceived stress (beta = 0.33, p < 0.05,
      DeltaR(2 )= 0.106). This is the first study showing that objectively assessed VPA
      is associated with increased hair cortisol levels in young adults. As VPA can be
      regarded as a physical stressor, it seems imperative that researchers consider
      participants' levels of VPA if they examine the relationship between stress
      exposure, hair cortisol and health.

PMID- 23855827
TI  - Variable promoter methylation contributes to differential expression of key genes
      in human placenta-derived venous and arterial endothelial cells.
AB  - BACKGROUND: The endothelial compartment, comprising arterial, venous and
      lymphatic cell types, is established prenatally in association with rapid
      phenotypic and functional changes. The molecular mechanisms underpinning this
      process in utero have yet to be fully elucidated. The aim of this study was to
      investigate the potential for DNA methylation to act as a driver of the specific
      gene expression profiles of arterial and venous endothelial cells. RESULTS:
      Placenta-derived venous and arterial endothelial cells were collected at birth
      prior to culturing. DNA methylation was measured at >450,000 CpG sites in
      parallel with expression measurements taken from 25,000 annotated genes. A
      consistent set of genomic loci was found to show coordinate differential
      methylation between the arterial and venous cell types. This included many loci
      previously not investigated in relation to endothelial function. An inverse
      relationship was observed between gene expression and promoter methylation levels
      for a limited subset of genes implicated in endothelial function, including NOS3,
      encoding endothelial Nitric Oxide Synthase. CONCLUSION: Endothelial cells derived
      from the placental vasculature at birth contain widespread methylation of key
      regulatory genes. These are candidates involved in the specification of different
      endothelial cell types and represent potential target genes for environmentally
      mediated epigenetic disruption in utero in association with cardiovascular
      disease risk later in life.

PMID- 23855830
TI  - Unusual phase behavior in the piezoelectric perovskite system, Li(x)Na(1-x)NbO3.
AB  - The system Li(x)Na(1-x)NbO3 has been studied by using a combination of X-ray and
      neutron powder diffraction and (23)Na solid-state NMR spectroscopy. For x = 0.05
      we confirm a single polar orthorhombic phase. For 0.08 <= x <= 0.20 phase
      mixtures of this orthorhombic phase, together with a rhombohedral phase,
      isostructural with the low-temperature ferroelectric polymorph of NaNbO3, are
      observed. The relative fractions of these two phases are shown to be critically
      dependent on synthetic conditions: the rhombohedral phase is favored by higher
      annealing temperatures and rapid cooling. We also observe that the orthorhombic
      phase transforms slowly to the rhombohedral phase on standing in air at ambient
      temperature. For 0.25 <= x <= 0.90 two rhombohedral phases coexist, one Na-rich
      and the other Li-rich. In this region the phase behavior is independent of
      reaction conditions.

PMID- 23855829
TI  - Prevalence and risk factors of posterior vitreous detachment in a Chinese adult
      population: the Handan eye study.
AB  - BACKGROUND: To describe the prevalence and associations of posterior vitreous
      detachment (PVD) in a rural adult Chinese population. METHODS: All eligible
      subjects were requested to carry out a comprehensive eye examination; PVD was a
      pre-specified outcome variable and was determined via biomicroscopical
      examination (slit-lamp biomicroscopy) with a +90-D preset lens after mydriasis.
      Prevalence was standardized to China population census (2000). RESULTS: 5890
      (86.2%) subjects completed the examination of slit-lamp biomicroscopy with a +90
      D lens. PVD was present in 160 participants (2.7%); the standardized prevalence
      was 2.0% (95% confidence interval [CI], 1.6-2.3%). PVD developed increasingly
      with age (P for trend < 0.001) for both men and women. Using a multivariate
      regression model, older people were found to run a higher risk of developing PVD
      than younger people, and women were found to have a higher risk than men (OR,
      2.9; 95% CI, 1.5-5.9). Diabetes, hypertension, smoking, drinking, and intraocular
      pressure (IOP) were not significantly associated with PVD. CONCLUSIONS: About one
      in fifty people is found to have PVD in this population-based study. Age and
      female are independently associated with PVD occurrence.

PMID- 23855831
TI  - Role of order during Ogston sieving of DNA in colloidal crystals.
AB  - We combine in situ Bragg diffraction, laser diffraction, high speed fluorescence
      scanning, and large-scale data processing to arrive at statistically significant
      conclusions about the role of order during the microchip electrophoresis
      separation of short DNA molecules (86 base pairs and 709 base pairs) in colloidal
      crystals. This experimental approach directly connects the presence of long-range
      order (obtained by laser diffraction) to the DNA transport (obtained by
      fluorescence detection) in hundreds of "mini-columns" composed of 500 MUm-long
      regions of the devices. To within statistical significance, the electrophoretic
      mobility is the same in regions of the chip with long-range order and those with
      short-range order, independent of the electric field and molecular weight.
      Moreover, the relative mobilities of the DNA agree well with a recent estimate
      for the Ogston sieving mobility in a colloidal crystal. Similar to previous work,
      the band broadening during the transit through the colloidal crystal is
      negligible. These features imply that colloidal crystals for DNA separation in
      the Ogston sieving regime do not require exquisite control over the
      microstructure to maximize the separation resolution, simplifying their assembly
      for routine use. 

PMID- 23855832
TI  - Molluscicidal and larvicidal activities and essential oil composition of
      Cymbopogon winterianus.
AB  - CONTEXT. Cymbopogon winterianus Jowitt ex Bor (Poaceae), known as citronella
      grass, is an aromatic herbaceous plant and the essential oil extracted from this
      grass is used in cosmetics, perfumes, hygiene and cleanliness products worldwide.
      OBJECTIVE: This study investigated the composition and molluscicidal and
      larvicidal activities of the essential oil of C. winterianus cultivated in North
      Brazil. MATERIALS AND METHODS: The oil was obtained by hydrodistillation,
      analyzed by gas chromatography (GC) and GC-mass spectrometry and then its
      molluscicidal and larvicidal activities against snails (Biomphalaria glabrata)
      and hatched larvae of Artemia salina, respectively, were evaluated at
      concentrations from 10 to 1000 mg/L. RESULTS: The main constituents of oil were
      citronellal (26.5%), geraniol (16.2%), elemol (14.5%) and citronellol (7.3%). The
      molluscicidal test revealed significant lethal concentration (LC) values
      (LC90=97.0 mg/L, LC50=54.0 mg/L and LC20=22.0 mg/L), indicating the presence of
      molluscicidal compounds in the oil. In addition, the oil showed moderate
      larvicidal activity (LC50=181.0 mg/L) against the larvae of A. salina, which
      could justify its use in the aquatic environment without affecting other living
      organisms. DISCUSSION AND CONCLUSION: The results suggest that the oil of C.
      winterianus could be an effective alternative to control schistosomiasis, with an
      average margin of safety to other living organisms that coexist with snails.

PMID- 23855833
TI  - Simultaneous double atrial flutters depending on the cavotricuspid and mitral
      isthmuses.

PMID- 23855834
TI  - Genetic diversity of Plasmodium falciparum and distribution of drug resistance
      haplotypes in Yemen.
AB  - BACKGROUND: Despite evident success of malaria control in many sites in the
      Arabian Peninsula, malaria remains endemic in a few spots, in Yemen and south
      west of Saudi Arabia. In addition to local transmission, imported malaria
      sustains an extra source of parasites that can challenge the strengths of local
      control strategies. This study examined the genetic diversity of Plasmodium
      falciparum in Yemen and mutations of drug resistant genes, to elucidate parasite
      structure and distribution of drug resistance genotypes in the region. METHODS:
      Five polymorphic loci (MSP-2, Pfg377 and three microsatellites on chromosome 8)
      not involved in anti-malarial drug resistance, and four drug resistant genes
      (pfcrt, pfmdr1, dhfr and dhps) were genotyped in 108 P. falciparum isolates
      collected in three sites in Yemen: Dhamar, Hodeidah and Taiz. RESULTS: High
      diversity was seen in non-drug genes, pfg377 (He = 0.66), msp-2 (He = 0.80) and
      three microsatellites on chr 8, 7.7 kb (He = 0.88), 4.3 kb (He = 0.77) and 0.8 kb
      (He = 0.71). There was a high level of mixed-genotype infections (57%), with an
      average 1.8 genotypes per patient. No linkage disequilibrium was seen between
      drug resistant genes and the non-drug markers (p < 0.05). Genetic differentiation
      between populations was low (most pair-wise FST values <0.03), indicating
      extensive gene flow between the parasites in the three sites. CONCLUSION: The
      high diversity of P. falciparum in Yemen is indicative of a large parasite
      reservoir, which represents a challenge to control efforts. The presence of two
      distinct pfcrt genotype, CVIET and SVMNT, suggests that chloroquine resistance
      can possibly be related to a migratory path from Africa and Asia. The absence of
      the triple mutant dhfr genotype (IRN) and dhps mutations supports the use of
      artesunate + sulphadoxine-pyrimethamine as first-line therapy. However, the
      prevalent pfmdr1 genotype NFSND [21%] has previously been associated with
      tolerance/resistance response to artemisinin combination therapy (ACT). Regular
      surveys are, therefore, important to monitor spread of pfmdr1 and dhfr mutations
      and response to ACT.

PMID- 23855835
TI  - Enhanced and aberrant T cell trafficking following total body irradiation: a
      gateway to graft-versus-host disease?
AB  - Pre-transplant conditioning regimens play a major role in triggering graft-versus
      host disease (GVHD). This study investigated the effect of irradiation on donor T
      cell trafficking to lymphoid and non-lymphoid tissues by comparing the migration
      of carboxy-fluorescein diacetate succinimidyl ester-labelled, naive donor T
      lymphocytes in vivo in irradiated and non-irradiated syngeneic mice recipients.
      Recruitment of adoptively transferred naive T cells to secondary lymphoid organs
      was increased in irradiated mice and naive T cells also aberrantly localized to
      non-lymphoid tissues. Irradiation also induced aberrant effector memory T cell
      migration into lymph nodes and their localization to homing-privileged non
      lymphoid sites, such as the gut. The presence of a minor histocompatibility
      mismatch further enhanced the aberrant accumulation of T cells in both lymphoid
      and non-lymphoid tissue, whilst their migratory pattern was not modified as
      compared to fully matched irradiated recipients. These effects correlated with
      decreased permeability of, and the secretion of chemotactic factors by the
      endothelium. Our findings are consistent with the possibility that excessive,
      dysregulated extravasation of T cells induced by irradiation promotes the
      development of GVHD. 

PMID- 23855836
TI  - 1-substituted (Dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-ones endowed
      with dual DNA-PK/PI3-K inhibitory activity.
AB  - Analogues of (dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one (NU7441),
      a potent inhibitor of DNA-dependent protein kinase (DNA-PK; IC50 = 42 +/- 2 nM),
      have been synthesized in which water-solubilizing groups [NHCO(CH2)nNR1R2, where
      n = 1 or 2 and the moiety R1R2N was derived from a library of primary and
      secondary amines, e.g., morpholine] were placed at the 1-position. Several of the
      newly synthesized compounds exhibited high potency against DNA-PK and potentiated
      the cytotoxicity of ionizing radiation (IR) in vitro 10-fold or more (e.g., 2-(4
      ethylpiperazin-1-yl)-N-(4-(2-morpholino-4-oxo-4H-chromen-8-yl)dibenzo[b,d]thio
      phen-1-yl)acetamide, 39; DNA-PK IC50 = 5.0 +/- 1 nM, IR dose modification ratio =
      13). Furthermore, 39 was shown to potentiate not only IR in vitro but also DNA
      inducing cytotoxic anticancer agents, both in vitro and in vivo. Counter
      screening against other members of the phosphatidylinositol 3-kinase (PI-3K)
      related kinase (PIKK) family unexpectedly revealed that some of the compounds
      were potent mixed DNA-PK and PI-3K inhibitors.

PMID- 23855837
TI  - Thermodynamic and kinetic destabilization of magnesium hydride using Mg-In solid
      solution alloys.
AB  - Efforts to thermodynamically destabilize magnesium hydride (MgH2), so that it can
      be used for practical hydrogen storage applications, have been a difficult
      challenge that has eluded scientists for decades. This letter reports that MgH2
      can indeed be destabilized by forming solid solution alloys of magnesium with
      group III and IVB elements, such as indium. Results of this research showed that
      the equilibrium hydrogen pressure of a Mg-0.1In alloy is 70% higher than that of
      pure MgH2. The temperature at 1 bar hydrogen pressure (T1bar) of Mg-0.1In alloy
      was reduced to 262.9  degrees C from 278.9  degrees C, which is the T1bar of pure
      MgH2. Furthermore, the kinetic rates of dehydrogenation of Mg-0.1In alloy hydride
      doped with a titanium intermetallic (TiMn2) catalyst were also significantly
      improved compared with those of MgH2.

PMID- 23855838
TI  - Evaluating the value and impact of the Victorian Audit of Surgical Mortality.
AB  - INTRODUCTION: Since the Victorian Audit of Surgical Mortality (VASM) commenced in
      2007, 95% of Victorian Fellows have agreed to participate and have provided data
      on the deaths of patients receiving surgical care. All public, and the majority
      of private, hospitals involved in the delivery of surgical services in Victoria
      have been submitting data on deaths associated with surgery. De-identified
      reports on this data are distributed in regular annual reports and case note
      review booklets. Although informal feedback on the perceived value of the audit
      was encouraging, a formal review of all aspects of the audit was felt necessary.
      METHODS: An independent formal review of VASM governance, documentation, datasets
      and data analysis was performed, in addition to a survey of 257 individuals
      (surgeons and other stakeholders) on the perceived impact of VASM. RESULTS: The
      review confirmed increasing participation and acceptance by surgeons since the
      inception of the project. Governance mechanisms were found to be effective and
      acknowledged by stakeholders and collaborators. Robust participation rates have
      been achieved, and stakeholders were generally satisfied with the quality of
      feedback. Suggestions for improvement were provided by some surgeons and
      hospitals. CONCLUSION: External review of VASM processes and procedures confirmed
      that the audit was operating effectively, with robust quality control and
      achieving the trust of stakeholders. The educational value of the audit to the
      surgical community was acknowledged and areas for future improvement have been
      identified.

PMID- 23855839
TI  - Aminoguanidine inhibits the AGE-RAGE axis to modulate the induction of
      periodontitis but has limited effects on the progression and recovery of
      experimental periodontitis: a preliminary study.
AB  - BACKGROUND: Advanced glycation end products (AGE) have been found in inflamed
      gingival tissue and have been shown to interfere with the integrity of
      extracellular matrix and cell-matrix interactions. This study aims to investigate
      the modulatory effect of aminoguanidine (AG), an AGE inhibitor, in various stages
      of experimental periodontitis. METHODS: Thirty-six Sprague-Dawley rats were used.
      AG or normal saline (NS) was systemically administered in the induction,
      progression, and recovery phases of ligature-induced periodontitis. Dynamic
      changes of the periodontium were evaluated by microcomputed tomography,
      histology, and immunohistochemistry of the receptor for AGE (RAGE). Molecular
      mechanisms were evaluated by myeloperoxidase activity, gene expression of RAGE,
      and markers associated with tissue repair and homeostasis, including vascular
      endothelial growth factor (VEGF), type I collagen, fibronectin, and periostin.
      RESULTS: AG appeared to inhibit the degradation of the collagen matrix in the
      induction phase but promoted collagen reorganization in the progression and
      recovery phases of experimental periodontitis. In the induction sites,
      periodontal bone loss was significantly reduced (P <0.05), with significantly
      reduced RAGE (P <0.05) and significantly elevated fibronectin and periostin
      levels (P <0.01). No significant alterations in the levels of myeloperoxidase,
      VEGF, and collagen were noted. In the progression and recovery sites, similar
      trends were observed, with insignificant differences relative to NS-treated
      animals. CONCLUSIONS: AG reduced periodontal bone loss during the induction of
      experimental periodontitis, and the effects appeared to be insignificant in the
      progression and recovery phases. This modulation was related to the inhibition of
      the AGE-RAGE axis to resume cell-matrix interactions and maintain tissue
      integrity.

PMID- 23855840
TI  - Efficacy of preprocedural mouth rinsing in reducing aerosol contamination
      produced by ultrasonic scaler: a pilot study.
AB  - BACKGROUND: The aerosol generated by an ultrasonic scaler contains microorganisms
      that can penetrate into the body through the respiratory system of dental
      surgeons and patients. The aim of this pilot study is to evaluate and compare the
      efficacy of commercially available preprocedural mouthrinses containing 0.2%
      chlorhexidine gluconate, an herbal mouthwash, and water in reducing the levels of
      viable bacteria in aerosols. METHODS: This single-center, double-masked, placebo
      controlled, randomized, three-group parallel design was conducted over a period
      of 45 days. Twenty-four patients with chronic periodontitis were divided randomly
      into three groups (A, B, and C) of eight patients each to receive 0.2%
      chlorhexidine gluconate, herbal mouthwash, and water, respectively, as a
      preprocedural rinse. The aerosol produced by the ultrasonic unit was collected at
      patient's chest area, doctor's chest area, and assistant's chest area on blood
      agar plates in all three groups. The blood agar plates were incubated at 37
      degrees C for 48 hours, and the total number of colony-forming units (CFUs) was
      counted and statistically analyzed. RESULTS: The results showed that CFUs in
      groups A and B were significantly reduced compared with group C, P <0.001
      (analysis of variance). Also, CFUs in group A were significantly reduced compared
      with group B, P <0.05 (independent t-test). The numbers of CFUs were highest at
      the patient's chest area and lowest at the assistant's chest area. CONCLUSION:
      This study suggests that a routine preprocedural mouthrinse could eliminate the
      majority of bacterial aerosols generated by the use of an ultrasonic unit, and
      that 0.2% chlorhexidine gluconate is more effective than herbal mouthwash.

PMID- 23855841
TI  - Total synthesis of a pyrroloindoloquinazoline alkaloid.
AB  - A highly concise stereoselective synthesis of a newly identified alkaloid with a
      pyrroloindoloquinazoline skeleton has been achieved. To this end, a chiral
      auxiliary mediated asymmetric acetate aldol reaction on tryptanthrin was explored
      and the resulting adduct was converted to the product by a novel one-pot
      reductive cyclization/transamidation using NiCl2.6H2O/NaBH4 in methanol. 

PMID- 23855842
TI  - Objective measures of physical activity, fractures and falls: the osteoporotic
      fractures in men study.
AB  - OBJECTIVES: To determine the association between objectively measured physical
      activity (PA), fractures, and falls. DESIGN: Longitudinal cohort study. SETTING:
      Six U.S. clinical sites. PARTICIPANTS: Two thousand seven hundred thirty-one men
      with a mean age of 79. MEASUREMENTS: Total and active energy expenditure (EE) and
      minutes per day spent in sedentary and moderate intensity activities were
      measured for at least 5 days. Energy expended at a metabolic equivalent of
      greater than three was termed active EE. Incident nonspine fractures and falls
      were identified every 4 months. RESULTS: Seven hundred fifty-nine (28.2%) men
      fell at least once over 12 months of follow-up; 186 (6.8%) experienced one or
      more fractures over an average follow-up of 3.5 +/- 0.9 years. The association
      between PA and falling varied according to age (P interaction = .02). Men younger
      than 80 with the lowest active EE had a lower risk of falling than men with the
      highest active EE (relative risk (RR) = 0.75; P trend = .08), whereas men aged 80
      and older with the lowest active EE had a higher risk of falling than men with
      the highest active EE (RR = 1.43, P trend = .09). In multivariate models
      including health status, men in the lowest quintile of active EE had a
      significantly higher risk of fracture (hazard ratio (HR) = 1.82, 95% confidence
      interval (CI) = 1.10-3.00, P trend = .04) than men in highest quintile. Men with
      <33 min/d of moderate activity had a 70% greater risk of fracture (HR = 1.70, 95%
      CI = 1.03-2.80). CONCLUSION: Age modifies the association between PA and falling.
      Interventions aimed at obtaining more than 30 minutes of moderate PA per day may
      reduce fractures, extending PA guidelines to the oldest old, the fastest-growing
      proportion of those aged 65 and older.

PMID- 23855844
TI  - Systolic hypertension should not be treated in persons aged 80 and older until
      blood pressure is greater than 160 mmHg.

PMID- 23855843
TI  - Inappropriate medication prescriptions in elderly adults surviving an intensive
      care unit hospitalization.
AB  - OBJECTIVES: To determine types of potentially (PIMs) and actually inappropriate
      medications (AIMs), which PIMs are most likely to be considered AIMs, and risk
      factors for PIMs and AIMs at hospital discharge in elderly intensive care unit
      (ICU) survivors. DESIGN: Prospective cohort study. SETTING: Tertiary care,
      academic medical center. PARTICIPANTS: One hundred twenty individuals aged 60 and
      older who survived an ICU hospitalization. MEASUREMENTS: Potentially
      inappropriate medications were defined according to published criteria; a
      multidisciplinary panel adjudicated AIMs. Medications from before admission, ward
      admission, ICU admission, ICU discharge, and hospital discharge were abstracted.
      Poisson regression was used to examine independent risk factors for hospital
      discharge PIMs and AIMs. RESULTS: Of 250 PIMs prescribed at discharge, the most
      common were opioids (28%), anticholinergics (24%), antidepressants (12%), and
      drugs causing orthostasis (8%). The three most common AIMs were anticholinergics
      (37%), nonbenzodiazepine hypnotics (14%), and opioids (12%). Overall, 36% of
      discharge PIMs were classified as AIMs, but the percentage varied according to
      drug type. Whereas only 16% of opioids, 23% of antidepressants, and 10% of drugs
      causing orthostasis were classified as AIMs, 55% of anticholinergics, 71% of
      atypical antipyschotics, 67% of nonbenzodiazepine hypnotics and benzodiazepines,
      and 100% of muscle relaxants were deemed AIMs. The majority of PIMs and AIMs were
      first prescribed in the ICU. Preadmission PIMs, discharge to somewhere other than
      home, and discharge from a surgical service predicted number of discharge PIMs,
      but none of the factors predicted AIMs at discharge. CONCLUSION: Certain types of
      PIMs, which are commonly initiated in the ICU, are more frequently considered
      inappropriate upon clinical review. Efforts to reduce AIMs in elderly ICU
      survivors should target these specific classes of medications.

PMID- 23855845
TI  - Healthy people aged 80 and older with systolic blood pressure greater than 150
      mmHg should be treated.

PMID- 23855846
TI  - Response to John Morley.

PMID- 23855847
TI  - Response to Mark Supiano.

PMID- 23855848
TI  - The body-mind connection in aging and dementia.

PMID- 23855849
TI  - Quality of hospice care for individuals with dementia.

PMID- 23855850
TI  - Traveling in the world of patients.

PMID- 23855851
TI  - Utility and acceptability of the modified Telephone Interview for Cognitive
      Status in a longitudinal study of Australian women aged 85 to 90.

PMID- 23855852
TI  - Epidemiological studies on shoes for elderly adults in a geriatric unit.

PMID- 23855853
TI  - Transabdominal ultrasound finding and acute hepatocellular injury in different
      cohorts of elderly adults with and without common bile duct stones.

PMID- 23855854
TI  - Number of drug classes taken per day may be used to assess morbidity burden in
      older inpatients: a pilot cross-sectional study.

PMID- 23855855
TI  - Challenges of adequate road crossing time for older persons: a pilot study in
      Singapore.

PMID- 23855856
TI  - A standard international version of the Drug Burden Index for cross-national
      comparison of the functional burden of medications in older people.

PMID- 23855857
TI  - Homeostasis model assessment in elderly adults without diabetes mellitus.

PMID- 23855858
TI  - Latin American experience with Alzheimer's disease cerebrospinal fluid
      biomarkers.

PMID- 23855859
TI  - Alzheimer's disease correlates with greater risk of hip fracture in older people:
      a cohort in Taiwan.

PMID- 23855860
TI  - Genetic effects on life-space mobility in older women.

PMID- 23855861
TI  - Comparable incremental value of standard and nonstandard lipids for coronary
      heart disease risk assessment in elderly adults: the Three City Study.

PMID- 23855862
TI  - Fear of falling, falls, and gait variability in older community-dwelling
      individuals: is there an association?

PMID- 23855863
TI  - "Just make it stop": a case report of excessive crying in an individual with
      dementia.

PMID- 23855864
TI  - Recurrent and consistent improvement of cognitive impairment and depression after
      short time of treatment with enoxaparin.

PMID- 23855865
TI  - Dunbar syndrome: an old cause of a new clinical picture in an older adult.

PMID- 23855866
TI  - Cerebral venous thrombosis in an elderly adult treated with diethylstilbestrol.

PMID- 23855867
TI  - A case of paraneoplastic syndrome mimicking adult Still's disease caused by
      rectal cancer.

PMID- 23855868
TI  - Case report: Nausea and vomiting caused by a rare case of gastric volvulus.

PMID- 23855869
TI  - Current federal budget issues and the impact on academic geriatricians.

PMID- 23855870
TI  - Slaying dementia dragons.

PMID- 23855871
TI  - Picture-based memory impairment screen: a major achievement for cognitive
      assessment of older adults in developing countries.

PMID- 23855872
TI  - Response letter to Drs. Vidal, Villas Boas, Valle, and Fukushima.

PMID- 23855873
TI  - Laser annealing of nanocrystalline gold nanowires.
AB  - The efficacy of laser annealing for the thermal annealing of nanocrystalline gold
      nanowires is evaluated. Continuous laser illumination at 532 nm, focused to a 0.5
      MUm diameter spot, was rastered perpendicular to the axis of nanocrystalline gold
      nanowire at ~2 kHz. This rastered beam was then scanned down the nanowire at
      velocities from 7 to 112 nm/s. The influence on the electrical resistance of the
      gold nanowire of laser power, polarization, translation speed, and nanowire width
      were evaluated. Nanocrystalline gold nanowires were prepared on glass surfaces
      using the lithographically patterned nanowire electrodeposition (LPNE) method.
      These nanowires had a rectangular cross section with a height of 20 (+/- 3) nm
      and widths ranging from 76 to 274 nm. The 4-contact electrical resistance of the
      nanowire is measured in situ during laser annealing and a real-time decrease in
      electrical resistance of between 30 and 65% is observed, depending upon the laser
      power and scan rate along the nanowire. These resistance decreases are associated
      with an increase in the mean grain diameter within these nanowires, measured
      using transmission electron microscopy, of up to 300%. The observed decrease in
      the electrical resistance induced by laser annealing conforms to classical
      predictions based upon the reduction in grain boundary scattering induced by
      grain growth. 

PMID- 23855874
TI  - Prevalence, causes, severity, impact, and management of chronic pain in
      Australian general practice patients.
AB  - OBJECTIVE: To determine the prevalence of chronic pain, its causes, severity,
      management, impact on sleep, mood and activity levels, and general practitioner
      (GP) and patient satisfaction with pain management. DESIGN: A subset of 197 GPs
      and 5,793 patients from the BEACH program, a continuous, national cross-sectional
      survey of Australian general practice. RESULTS: The prevalence of chronic pain
      was 19.2% (95% confidence interval: 17.4-21.0) (N = 1,113). The most commonly
      reported causal conditions were osteoarthritis (48.1%) and back problems (29.4%).
      For pain severity (using Von Korff's pain grades), 25.2% were at Grade I
      (lowest); 37.1% were at Grade II; 28.3% at Grade III; and 9.4% at Grade IV
      (highest). Medication was used for pain management by 86.1% of patients, and one
      third also used nonpharmacological managements. One third of patients were taking
      opioids, most commonly those at the highest pain severity grades. On "Live Better
      with Pain Log" scale, the impact of pain was similar across activity (mean =
      4.0), sleep (mean = 4.8), and mood (mean = 4.8). On a scale of 1 (highest) to 5
      (lowest), GPs' satisfaction (mean = 2.5) was highly correlated (r = 0.7) with
      patients' satisfaction (mean = 2.6) with pain management. CONCLUSIONS: Chronic
      pain impairs patient quality of life, and is a public health burden. This study
      provides a national overview of the prevalence, causes, severity, management and
      impact of chronic pain in Australian general practice patients, and the parity
      between GP and patient satisfaction with pain management.

PMID- 23855876
TI  - Hypothalamic distribution of somatostatin mRNA expressing neurones relative to
      pubertal and adult changes in pulsatile growth hormone secretion in mice.
AB  - The age-associated decline in growth hormone (GH) secretion may be a consequence
      of the reduction in the number of GH-releasing hormone (GHRH) positive neurones.
      However, it remains unclear whether an alteration in the number or distribution
      of somatostatin (SST) neurones contributes to this change. In the present study,
      we characterised the role of SST in modulating the change in pulsatile GH
      secretion in male C57Bl/6J mice throughout puberty and into early adulthood. We
      assessed pulsatile GH secretion in mice at 4, 8 and 16 weeks of age. These ages
      correspond to early pubertal, early adulthood and adulthood, respectively. We
      show an elevation in peak, total and pulsatile GH secretion coinciding with
      periods of rapid linear growth. Using in situ hybridisation and morphometric
      methods, we mapped the distribution of Sst mRNA expression within the mouse brain
      relative to this change in pulsatile GH secretion. The results obtained show that
      altered pulsatile GH secretion in male mice from 4-16 weeks of age does not
      coincide with a significant change in the number of Sst mRNA expressing neurones
      or an abundance of Sst mRNA expression throughout the arcuate nucleus (ARC) and
      periventricular nucleus (PeV). Rather, we observed a progressive decline in Sst
      mRNA expressing neurones within subnuclei of the paraventricular nucleus at this
      time. We conclude that structural changes in Sst expression within the PeV and
      ARC may not reflect the observed decline in pulsatile GH secretion in mice from
      puberty into early adulthood. 

PMID- 23855875
TI  - Long-lasting antifouling coating from multi-armed polymer.
AB  - We describe a new antifouling surface coating, based on aggregation of a short
      amphiphilic four-armed PEG-dopamine polymer into particles and on surface binding
      by catechol chemistry. An unbroken and smooth polymeric coating layer with an
      average thickness of approximately 4 MUm was formed on top of titanium oxide
      surfaces by a single step reaction. Coatings conferred excellent resistance to
      protein adhesion. Cell attachment was completely prevented for at least eight
      weeks, although the membranes themselves did not appear to be intrinsically
      cytotoxic. When linear PEG or four-armed PEG of higher molecular weight were
      used, the resulting coatings were inferior in thickness and in preventing protein
      adhesion. This coating method has potential applicability for biomedical devices
      susceptible to fouling after implantation. 

PMID- 23855877
TI  - Towards personalizing haemophilia care: using the Haemophilia Severity Score to
      assess 178 patients in a single institution.
AB  - The phenotypic variability in haemophilia is well documented; however, the
      biological basis beyond factor VIII and IX activities to explain the differing
      clinical pictures of the disease remains unclear. It has therefore been of
      interest to explore other modulators of the disease's variability. Furthermore, a
      scoring system that reflects the multiple facets of haemophilia symptoms would be
      useful to compare patients via a comprehensive assessment tool. To this end,
      Schulman et al., created a measure known as the Haemophilia Severity Score (HSS)
      as one way to compare phenotypic severity. The aim of this study was to document
      the differing symptomatology of haemophilia patients using the HSS. Clinical data
      for 178 haemophilia patients without inhibitors were reviewed and annual
      incidence of haemarthrosis, orthopaedic joint scores and annual factor usage
      calculated. Each parameter was then entered into the formula to create the HSS
      for haemophilia A and B patients with mild, moderate and severe factor
      deficiencies. Variability in the HSS for patients with the same baseline level of
      factor was observed for all three deficiency levels and both haemophilia types.
      In addition, we found that moderate and severe haemophilic B patients tended to
      have more morbidity based on the above calculations than the haemophilic A
      counterparts. The HSS is a comprehensive tool that allows for easy numerical
      comparison of haemophilic patients and elucidates the variable clinical
      presentation of the disease. The HSS could be used to stratify patients via other
      possible modulators of haemophilia and discover other aetiologies of the disease.

PMID- 23855880
TI  - The role of potatoes and potato components in cardiometabolic health: a review.
AB  - Potatoes (Solanum tuberosum) are an important food crop worldwide and contribute
      key nutrients to the diet, including vitamin C, potassium, and dietary fiber.
      Potatoes and potato components have been shown to have favorable impacts on
      several measures of cardiometabolic health in animals and humans, including
      lowering blood pressure, improving lipid profiles, and decreasing markers of
      inflammation. A range of glycemic index (GI) values have been reported for
      potatoes, and data are sparse regarding the impact of potato consumption on the
      postprandial glycemic response, especially when potatoes are consumed with other
      foods. There is a lack of clinical trial data regarding the impact of potatoes on
      weight management. A small number of human cohort studies have reported
      beneficial associations between potato consumption as part of a healthy lifestyle
      and cardiometabolic health. Another small number of human population studies have
      included potatoes as part of a dietary pattern with other calorie-dense foods and
      have not reported cardiometabolic benefits. The epidemiological literature should
      be interpreted with caution due to lack of consistency in both defining dietary
      patterns that include potatoes and in control for potential confounding
      variables. Controlled clinical trials are needed to define the impact of potatoes
      on cardiometabolic health.

PMID- 23855879
TI  - Cytokine and chemokine responses to helminth and protozoan parasites and to
      fungus and mite allergens in neonates, children, adults, and the elderly.
AB  - BACKGROUND: In rural sub-Saharan Africa, endemic populations are often infected
      concurrently with several intestinal and intravascular helminth and protozoan
      parasites. A specific, balanced and, to an extent, protective immunity will
      develop over time in response to repeated parasite encounters, with immune
      responses initially being poorly adapted and non-protective. The cellular
      production of pro-inflammatory and regulatory cytokines and chemokines in
      response to helminth, protozoan antigens and ubiquitous allergens were studied in
      neonates, children, adults and the elderly. RESULTS: In children schistosomiasis
      prevailed (33%) while hookworm and Entamoeba histolytica/E. dispar was found in
      up to half of adults and the elderly. Mansonella perstans filariasis was only
      present in adults (24%) and the elderly (25%). Two or more parasite infections
      were diagnosed in 41% of children, while such polyparasitism was present in 34%
      and 38% of adults and the elderly. Cytokine and chemokine production was
      distinctively inducible by parasite antigens; pro-inflammatory Th2-type cytokine
      IL-19 was activated by Entamoeba and Ascaris antigens, being low in neonates and
      children while IL-19 production enhanced "stepwise" in adults and elderly. In
      contrast, highest production of MIP-1delta/CCL15 was present in neonates and
      children and inducible by Entamoeba-specific antigens only. Adults and the
      elderly had enhanced regulatory IL-27 cytokine responses, with Th2-type
      chemokines (MCP-4/CCL13, Eotaxin-2/CCL24) and cytokines (IL-33) being notably
      inducible by helminth- and Entamoeba-specific antigens and fungus-derived
      allergens. The lower cellular responsiveness in neonates and children highlighted
      the development of a parasite-specific cellular response profile in response to
      repeated episodes of exposure and re-infection. CONCLUSIONS: Following repeated
      exposure to parasites, and as a consequence of host inability to prevent or
      eliminate intestinal helminth or protozoa infections, a repertoire of immune
      responses will evolve with lessened pro-inflammatory and pronounced regulatory
      cytokines and chemokines; this is required for partial parasite control as well
      as for preventing inadequate and excessive host tissue and organ damage.

PMID- 23855881
TI  - Deciduoid mesothelial hyperplasia of the pelvic peritoneum.

PMID- 23855882
TI  - Epithelial-mesenchymal transition of the eccrine glands is involved in skin
      fibrosis in morphea.
AB  - Morphea is a type of localized scleroderma. It is a skin disease involving the
      development of fibrosis in the dermis and subcutaneous fat tissue beneath without
      a visceral lesion, and the cause is still unclear. An involvement of epithelial
      mesenchymal transition (EMT) has been reported as a cause of tissue fibrosis, but
      this was mostly observed in pulmonary and hepatic fibrosis, and the involvement
      of EMT in a skin disease, morphea, has not been studied . Thus, we analyzed the
      involvement of EMT in skin fibrosis in morphea patients using pathological
      techniques. Skin lesions of six morphea patients were analyzed (five female and
      one male patient). As a control, non-light-exposed skin lesions of 11 healthy
      females were analyzed. Concretely, tissue samples were prepared from these
      subjects and subjected to immunostaining of transforming growth factor (TGF)
      beta1, alpha-smooth muscle actin (alpha-SMA) and fibronectin, which have been
      reported to be associated with fibrosis, and Snail1 and E-cadherin, which are
      considered to be involved in EMT, and expressions of these were analyzed. In
      morphea patients, dermal expression of TGF-beta1, alpha-SMA and fibronectin,
      which are involved in fibrosis, was enhanced, and, at the same time, enhanced
      expression of Snail1 and reduced expression of E-cadherin, which are involved in
      EMT, were observed in the dermal eccrine glands. These findings suggested the
      progression of EMT in the dermal eccrine glands in morphea. 

PMID- 23855883
TI  - Seasonality, weather and climate affect home range size in roe deer across a wide
      latitudinal gradient within Europe.
AB  - 1. Because many large mammal species have wide geographical ranges, spatially
      distant populations may be confronted with different sets of environmental
      conditions. Investigating how home range (HR) size varies across environmental
      gradients should yield a better understanding of the factors affecting large
      mammal ecology. 2. We evaluated how HR size of a large herbivore, the roe deer
      (Capreolus capreolus), varies in relation to seasonality, latitude (climate),
      weather, plant productivity and landscape features across its geographical range
      in Western Europe. As roe deer are income breeders, expected to adjust HR size
      continuously to temporal variation in food resources and energetic requirements,
      our baseline prediction was for HR size to decrease with proxies of resource
      availability. 3. We used GPS locations of roe deer collected from seven study
      sites (EURODEER collaborative project) to estimate fixed-kernel HR size at weekly
      and monthly temporal scales. We performed an unusually comprehensive analysis of
      variation in HR size among and within populations over time across the
      geographical range of a single species using generalized additive mixed models
      and linear mixed models, respectively. 4. Among populations, HR size decreased
      with increasing values for proxies of forage abundance, but increased with
      increases in seasonality, stochastic variation of temperature, latitude and snow
      cover. Within populations, roe deer HR size varied over time in relation to
      seasonality and proxies of forage abundance in a consistent way across the seven
      populations. Thus, our findings were broadly consistent across the distributional
      range of this species, demonstrating a strong and ubiquitous link between the
      amplitude and timing of environmental seasonality and HR size at the continental
      scale. 5. Overall, the variability in average HR size of roe deer across Europe
      reflects the interaction among local weather, climate and seasonality, providing
      valuable insight into the limiting factors affecting this large herbivore under
      contrasting conditions. The complexity of the relationships suggests that
      predicting ranging behaviour of large herbivores in relation to current and
      future climate change will require detailed knowledge not only about predicted
      increases in temperature, but also how this interacts with factors such as day
      length and climate predictability.

PMID- 23855884
TI  - Aortic stiffness measurement improves the prediction of asymptomatic coronary
      artery disease in stroke/transient ischemic attack patients.
AB  - BACKGROUND: Aortic stiffness is an independent predictor of coronary events.
      AIMS: We assessed the predictive value of aortic stiffness for >=50% asymptomatic
      coronary artery disease in a stroke/transient ischemic attack population.
      METHODS: We enrolled 300 consecutive patients aged 45-75 years with nondisabling,
      noncardioembolic ischemic stroke or transient ischemic attack, and no prior
      history of coronary artery disease. Coronary artery disease was assessed with 64
      section computed tomography coronary angiography and all patients had a detailed
      cervicocephalic arterial work-up. Aortic stiffness was determined from carotid
      femoral pulse wave velocity with 9.6 m/s as cutoff value. The predictive value of
      aortic stiffness was assessed by logistic regression and reclassification tables
      method after adjustment for the Framingham Risk Score and the presence of
      cervicocephalic stenosis, which were previously shown to be independent predictor
      of >=50% asymptomatic coronary artery disease. RESULTS: Among the 274 included
      patients who had computed tomography coronary angiography, 26% (95% CI, 21%-32%)
      had an increased stiffness (pulse wave velocity > 9.6 m/s) and 18% (14%-23%) had
      >=50% asymptomatic coronary artery disease. Increased aortic stiffness was
      associated with the presence of >=50% asymptomatic coronary artery disease, both
      in univariate (odds ratio = 3.4 [1.8-6.4]) and multivariate analyses (odds ratio
      = 2.3 [1.2-4.7]) after adjustment for Framingham Risk Score and presence of
      cervicocephalic stenosis. After carotid-femoral pulse wave velocity was added to
      the standard model including Framingham Risk Score and the presence of
      cervicocephalic stenosis, net reclassification improvement was 12.6% (P < 0.005),
      integrated discrimination index was 2.51% (P = 0.025), and model fit was improved
      (likelihood ratio = 4.99, P = 0.025). CONCLUSIONS: In stroke/transient ischemic
      attack patients, aortic pulse wave velocity improves the prediction of >=50%
      asymptomatic coronary artery disease beyond classical risk factors.

PMID- 23855886
TI  - Role played by isopropyl substituents in stabilizing the putative triple bond in
      Ar'EEAr' [E = Si, Ge, Sn; Ar' = C6H3-2,6-(C6H3-2,6-Pr(i)2)2] and Ar*PbPbAr* [Ar*
      = C6H3-2,6-(C6H2-2,4,6-Pr(i)3)2].
AB  - A theoretical study of the bonding in ArEEAr (where E = Si, Ge, Sn, Pb; Ar =
      terphenyl ligand) revealed for the first time why bulky isopropyl substituents
      electronically are required in order to isolate stable ArEEAr species. This was
      accomplished by combining the natural orbitals for chemical valence (NOCV) method
      with the extended transition state (ETS) scheme. The NOCV-ETS analysis was based
      on two ArE fragments in their doublet ground state with the configuration
      sigma(2)pi(1). For E = Si, Ge, and Sn, it revealed one pi-bond perpendicular to
      the CEEC plane and two sigma/pi-type bonds in the plane, whereas the ArPbPbAr
      system was found to have a single sigma bond with a C-Pb-Pb trans-bent angle
      close to 90 degrees . While similar bonding pictures have been obtained in
      previous model studies with Ar = H and CH3, the NOCV-ETS scheme was able to
      obtain quantitative estimates for the strength of various sigma/pi components
      without artificial truncations or twisting of the system. More importantly, NOCV
      ETS analysis was able to show that the electronic influence of the isopropyl
      substituents on the sigma/pi components differs little from that found in a
      system where they are replaced by hydrogen. Instead, the favorable role of the
      isopropyl substituents is due to dispersive van der Waals attractions between
      Pr(i) groups on aryl rings attached to different E atoms as well as
      hyperconjugation involving donation into sigma* orbitals on Pr(i). Dispersive
      interaction amounts to -27.5 kcal/mol (Si), -29.1 kcal/mol (Ge), -26.2 kcal/mol
      (Sn), and -44.0 kcal/mol (Pb). The larger dispersive stabilization for Pb
      reflects the fact that the longer Pb-Pb and Pb-C bonds sterically allow for more
      isopropyl groups with Ar = C6H3-2,6-(C6H2-2,4,6-Pr(i)3)2. This is compared to the
      other elements where Ar = C6H3-2,6-(C6H3-2,6-Pr(i)2)2. It is finally concluded
      from the analysis that real ArEEAr systems reveal little character of the EE bond
      in contrast to the findings of previous studies on model systems. 

PMID- 23855885
TI  - The miniature genome of a carnivorous plant Genlisea aurea contains a low number
      of genes and short non-coding sequences.
AB  - BACKGROUND: Genlisea aurea (Lentibulariaceae) is a carnivorous plant with
      unusually small genome size - 63.6 Mb - one of the smallest known among higher
      plants. Data on the genome sizes and the phylogeny of Genlisea suggest that this
      is a derived state within the genus. Thus, G. aurea is an excellent model
      organism for studying evolutionary mechanisms of genome contraction. RESULTS:
      Here we report sequencing and de novo draft assembly of G. aurea genome. The
      assembly consists of 10,687 contigs of the total length of 43.4 Mb and includes
      17,755 complete and partial protein-coding genes. Its comparison with the genome
      of Mimulus guttatus, another representative of higher core Lamiales clade,
      reveals striking differences in gene content and length of non-coding regions.
      CONCLUSIONS: Genome contraction was a complex process, which involved gene loss
      and reduction of lengths of introns and intergenic regions, but not intron loss.
      The gene loss is more frequent for the genes that belong to multigenic families
      indicating that genetic redundancy is an important prerequisite for genome size
      reduction.

PMID- 23855887
TI  - Tear lipid layer deficiency associated with incomplete blinking: a case report.
AB  - BACKGROUND: Meibomian gland obstruction induces hyposecretion of tear film
      lipids, which results in lipid layer deficiency and evaporative dry eye.
      Unfortunately, the importance of blinking in meibomian gland dysfunction has been
      largely overlooked, and it is not known whether incomplete blinking causes tear
      lipid deficiency, even in the unobstructed meibomian glands. CASE PRESENTATION: A
      38-year-old woman suffering from foreign body sensations in her eyes was
      examined. The cornea was clear and tear secretion was normal. Lid margin
      abnormalities were not observed and the meibum was clear. However, the lipid
      layer was very thin, and the patient was given a diagnosis of incomplete
      blinking. The patient was made aware of her condition and asked to blink
      consciously and completely. After that, an immediate increase in lipid flow was
      observed. CONCLUSION: Tear lipid layer deficiency can occur with incomplete
      blinking, even though meibomian gland structures are intact. This case highlights
      the importance of complete blinking.

PMID- 23855888
TI  - Anticancer activity of Saussurea lappa extract by apoptotic pathway in KB human
      oral cancer cells.
AB  - CONTEXT: Saussurea lappa Dence (Compositae) is used as a traditional herbal
      medicine to treat abdominal pain and tenesmus in East Asia. Current studies have
      shown that S. lappa has anticancer activity in divergent of cancer cells.
      However, the effects of S. lappa on oral cancer and its mechanisms of action have
      yet to be elucidated. OBJECTIVE: To explore its potential chemotherapeutic
      effects and mechanism of cell growth inhibition on human oral cancer cells.
      MATERIALS AND METHODS: The dried roots of S. lappa were used in this study. Cell
      viability of KB cells was evaluated by 3-[4, 5-dimethylthiazol-2-yl]-2, 5
      diphenyltetrazolium bromide assay after treatment with 30 ug/ml of methanol
      extract from the dried roots of S. lappa. To understand whether its effect on
      cell death is related with apoptosis pathway, we performed DNA fragmentation
      assay, western blot, caspase activity assay and fluorescence-activated cell
      sorting (FACS) analysis. RESULTS: Treatment of S. lappa extract onto KB cells
      reduced cell viability significantly with an IC50 value of 30 ug/ml. The
      formation of a DNA ladder was observed starting at the 24 h treatment. In western
      blotting analysis, the S. lappa extract induced the proteolytic processing of
      caspase-3, -9 and poly (ADP-ribose) polymerase, a significant increase of Bax and
      marked reduction of Bcl-2. We also confirmed the activation of caspase-3/-7 in
      living KB cells by fluorescence microscopy. CONCLUSION: These results suggested
      that S. lappa extract inhibited cell proliferation through the apoptosis pathway
      in KB human oral cancer cells.

PMID- 23855889
TI  - Exploring the orthosteric binding site of the gamma-aminobutyric acid type A
      receptor using 4-(Piperidin-4-yl)-1-hydroxypyrazoles 3- or 5-imidazolyl
      substituted: design, synthesis, and pharmacological evaluation.
AB  - A series of 4-(piperidin-4-yl)-1-hydroxypyrazole (4-PHP) 3- or 5-imidazolyl
      substituted analogues have been designed, synthesized, and characterized
      pharmacologically. All analogues showed binding affinities in the low micro- to
      low nanomolar range at native rat GABAA receptors and were found to be
      antagonists at the human alpha1beta2gamma2s receptor. The structure-activity
      relationship of the compound series demonstrates distinct differences in size and
      architecture of previously discovered cavities in the vicinity of the 4-PHP
      scaffold in the orthosteric binding site. 

PMID- 23855890
TI  - Separation of protein conformers by differential ion mobility in hydrogen-rich
      gases.
AB  - Proteins in solution or the gas phase tend to exhibit multiple conformational
      families, each comprising distinct structures. Separation methods have generally
      failed to resolve these, with their convolution producing wide peaks. Here, we
      report full separation of >10 conformers for most ubiquitin charge states by the
      new approach of differential ion mobility spectrometry (field asymmetric waveform
      ion mobility spectrometry, FAIMS) employing H2/N2 gas mixtures with up to 85% H2.
      The resolving power (up to 400) is five times the highest previously achieved
      (using He/N2 buffers), greatly increasing the separation specificity. The peak
      widths match the narrowest obtained by FAIMS for any species under the same
      conditions and scale with the protein charge state (z) and ion residence time (t)
      as z(-1/2) and t(-1/2), as prescribed for instrumental (diffusional) broadening.
      This suggests resolution of specific geometries rather than broader ensembles. 

PMID- 23855891
TI  - Delayed post-injury administration of C5a improves regeneration and functional
      recovery after spinal cord injury in mice.
AB  - The activation of a complement system can aggravate the secondary injury after
      spinal cord injury (SCI). However, it was reported recently that the activation
      of a complement could have both a secondary injury and a neuroprotective effect,
      in which C5a is the most important factor, but there is no direct evidence for
      this dual effect of C5a after SCI. In order to investigate the potential
      neuroprotective effect of C5a after SCI, in this study ectogenic C5a was injected
      intraperitoneally before/after SCI in vivo, or administrated to mechanically
      injured neurones in vitro; following this, neurone apoptosis, neurite outgrowth,
      axonal regeneration and functional recovery were investigated. The in-vivo
      experiments indicated that, following treatment with C5a 24 h before or
      immediately after injury, locomotor function was impaired significantly. However,
      when treatment with C5a took place 24 h after injury, locomotor function improved
      significantly. In-vitro experiments indicated that a certain concentration of C5a
      (50-100 nM) could inhibit caspase-3-mediated neurone apoptosis by binding to its
      receptor CD88, and that it could even promote the neurite outgrowth of uninjured
      neurones. In conclusion, delayed post-injury administration of C5a within a
      certain concentration could exert its neuroprotective effect through inhibiting
      caspase-3-mediated neurone apoptosis and promoting neurite outgrowth of uninjured
      neurones as well. These data suggest that C5a may have opposite functions in a
      time- and concentration-dependent manner after SCI. The dual roles of C5a have to
      be taken into account when measures are taken to inhibit complement activation in
      order to promote regeneration after SCI.

PMID- 23855892
TI  - High-resolution impedance manometry facilitates assessment of pharyngeal residue
      and oropharyngeal dysphagic mechanisms.
AB  - The utility of high-resolution impedance manometry (HRIM) for evaluating
      oropharyngeal dysphagia (OPD) has been investigated. These approaches are limited
      because of the sophisticated methodology. A method of transforming HRIM into a
      simple and useful diagnostic tool for evaluating OPD is needed. A
      videofluoroscopic swallowing study (VFSS) and HRIM were performed by independent
      blinded examiners in 26 consecutive healthy volunteers (12 men; median age, 56.5
      years) and 10 OPD patients (five men; median age, 59.5 years). Upper esophageal
      sphincter (UES) relaxation parameters were measured using a standard HRIM
      protocol. Peristalsis and bolus transit of the pharyngoesophageal (PE) segment
      were assessed using an HRIM-modified protocol in which the catheter was pulled
      back 10 cm. PE bolus transits were evaluated with an impedance contour pattern
      (linear vs. stasis) method. A significant difference was observed between the
      manometric measures of healthy volunteers and OPD patients for only the duration
      of pharyngeal contraction (0.49 +/- 0.19 vs. 0.76 +/- 0.33 s, P = 0.04). The
      percentage agreement and kappa value for detecting pharyngeal residue between the
      VFSS and the impedance analysis were 100% and 1.00, respectively. HRIM allowed
      for comprehensive assessment of abnormal pharyngeal components that caused
      pharyngeal residue on VFSS in two patients; reduced base of the tongue versus
      weak pharyngeal contraction in one, and reduced relaxation of the UES versus
      reduced laryngeal elevation in the remaining patient. Our findings demonstrated
      that HRIM using a simple methodology (i.e., pull-back of the catheter) detected
      pharyngeal residue through a simple analysis of the impedance contour pattern
      (linear vs. stasis). Furthermore, HRIM facilitated a comprehensive assessment of
      OPD mechanisms and recognition of subtle abnormalities not yet visible to the
      naked eye on VFSS. 

PMID- 23855894
TI  - Catalytic generation of borenium ions by cooperative B-H bond activation: the
      elusive direct electrophilic borylation of nitrogen heterocycles with
      pinacolborane.
AB  - The B-H bond of typical boranes is heterolytically split by the polar Ru-S bond
      of a tethered ruthenium(II) thiolate complex, affording a ruthenium(II) hydride
      and borenium ions with a dative interaction with the sulfur atom. These stable
      adducts were spectroscopically characterized, and in one case, the B-H bond
      activation step was crystallographically verified, a snapshot of the sigma-bond
      metathesis. The borenium ions derived from 9-borabicyclo[3.3.1]nonane dimer [(9
      BBN)2], pinacolborane (pinBH), and catecholborane (catBH) allowed for
      electrophilic aromatic substitution of indoles. The unprecedented electrophilic
      borylation with the pinB cation was further elaborated for various nitrogen
      heterocycles. 

PMID- 23855893
TI  - Exploring the impact of targeted distribution of free bed nets on households bed
      net ownership, socio-economic disparities and childhood malaria infection rates:
      analysis of national malaria survey data from three sub-Saharan Africa countries.
AB  - BACKGROUND: The last decade has witnessed increased funding for malaria control.
      Malaria experts have used the opportunity to advocate for rollout of such
      interventions as free bed nets. A free bed net distribution strategy is seen as
      the quickest way to improve coverage of effective malaria control tools
      especially among poorest communities. Evidence to support this claim is however,
      sparse. This study explored the effectiveness of targeted free bed net
      distribution strategy in achieving equity in terms of ownership and use of bed
      nets and also reduction of malaria prevalence among children under-five years of
      age. METHODS: National malaria indicator survey (MIS) data from Angola, Tanzania
      and Uganda was used in the analysis. Hierarchical multilevel logistic regression
      models were used to analyse the relationship between variables of interest.
      Outcome variables were defined as: childhood test-confirmed malaria infections,
      household ownership of any mosquito net and children's use of any mosquito nets.
      Marginal effects of having free bed net distribution on households with different
      wealth status were calculated. RESULTS: Angolan children from wealthier
      households were 6.4 percentage points less likely to be parasitaemic than those
      in poorest households, whereas those from Tanzania and Uganda were less likely to
      test malaria positive by 7 and 11.6 percentage points respectively (p < 0.001).
      The study estimates and present results on the marginal effects based on the
      impact of free bed net distribution on children's malaria status given their
      socio-economic background. Poorest households were less likely to own a net by
      21.4% in Tanzania, and 2.8% in Uganda, whereas both poorer and wealthier Angolan
      households almost achieved parity in bed net ownership (p < 0.001). Wealthier
      households had a higher margin of using nets than poorest people in both Tanzania
      and Uganda by 11.4% and 3.9% respectively. However, the poorest household in
      Angola had a 6.1% net use advantage over children in wealthier households (p <
      0.001). CONCLUSION: This is the first study to use nationally representative data
      to explore inequalities in bed net ownership and related consequences on
      childhood malaria infection rates across different countries. While targeted
      distribution of free bed nets improved overall bed net ownership, it did not
      overcome ownership inequalities as measured by household socioeconomic status.
      Use of bed nets was disproportionately lower among poorest children, except for
      Angola where bed net use was higher among poorest households when compared to
      children in wealthier households. The study highlights the need for malaria
      control world governing bodies and policy makers to continue working on finding
      appropriate strategies to improve access to effective malaria control tools
      especially by the poorest who often times bears the brunt of malaria burden than
      their wealthier counterparts.

PMID- 23855895
TI  - Updated thinking on positivity ratios.
AB  - This article presents my response to the article by Brown, Sokal, and Friedman
      (2013), which critically examined Losada's conceptual and mathematical work (as
      presented in Losada, 1999; Losada & Heaphy, 2004; and Fredrickson & Losada; 2005)
      and concluded that mathematical claims for a critical tipping point positivity
      ratio are unfounded. In the present article, I draw recent empirical evidence
      together to support the continued value of computing and seeking to elevate
      positivity ratios. I also underscore the necessity of modeling nonlinear effects
      of positivity ratios and, more generally, the value of systems science approaches
      within affective science and positive psychology. Even when scrubbed of Losada's
      now-questioned mathematical modeling, ample evidence continues to support the
      conclusion that, within bounds, higher positivity ratios are predictive of
      flourishing mental health and other beneficial outcomes.

PMID- 23855896
TI  - The complex dynamics of wishful thinking: the critical positivity ratio.
AB  - We examine critically the claims made by Fredrickson and Losada (2005) concerning
      the construct known as the "positivity ratio." We find no theoretical or
      empirical justification for the use of differential equations drawn from fluid
      dynamics, a subfield of physics, to describe changes in human emotions over time;
      furthermore, we demonstrate that the purported application of these equations
      contains numerous fundamental conceptual and mathematical errors. The lack of
      relevance of these equations and their incorrect application lead us to conclude
      that Fredrickson and Losada's claim to have demonstrated the existence of a
      critical minimum positivity ratio of 2.9013 is entirely unfounded. More
      generally, we urge future researchers to exercise caution in the use of advanced
      mathematical tools, such as nonlinear dynamics, and in particular to verify that
      the elementary conditions for their valid application have been met.

PMID- 23855897
TI  - Mild gut inflammation modulates the proteome of intestinal Escherichia coli.
AB  - Using interleukin 10-deficient (IL-10(-/-) ) and wild-type mice monoassociated
      with either the adherent-invasive Escherichia coli UNC or the probiotic E. coli
      Nissle, the effect of a mild intestinal inflammation on the bacterial proteome
      was studied. Within 8 weeks, IL-10(-/-) mice monoassociated with E. coli UNC
      exhibited an increased expression of several proinflammatory markers in caecal
      mucosa. Escherichia coli Nissle-associated IL-10(-/-) mice did not do so. As
      observed previously for E. coli from mice with acute colitis, glycolytic enzymes
      were downregulated in intestinal E. coli UNC from IL-10(-/-) mice. In addition,
      the inhibitor of vertebrate C-type lysozyme, Ivy, was upregulated on messenger
      RNA (mRNA) and protein level in E. coli Nissle from IL-10(-/-) mice compared with
      E. coli UNC from these mice. Higher expression of Ivy in E. coli Nissle
      correlated with an improved growth of this probiotic strain in the presence of
      lysozyme-ethylenediaminetetraacetic acid (EDTA). By overexpressing Ivy, we
      demonstrated that Ivy contributes to a higher lysozyme resistance of E. coli,
      supporting the role of Ivy as a potential fitness factor. However, deletion of
      Ivy did not alter the growth phenotype of E. coli Nissle in the presence of
      lysozyme-EDTA, suggesting the existence of additional lysozyme inhibitors that
      can take over the function of Ivy. 

PMID- 23855898
TI  - Comparison of the Baska((r)) mask with the single-use laryngeal mask airway in
      low-risk female patients undergoing ambulatory surgery.
AB  - We compared the Baska((r)) mask with the single-use classic laryngeal mask airway
      (cLMA) in 150 females at low risk for difficult tracheal intubation in a
      randomised, controlled clinical trial. We found that median (IQR [range]) seal
      pressure was significantly higher with the Baska mask compared with the cLMA (40
      (34-40 [16-40]) vs 22 (18-25 [14-40]) cmH2O, respectively, p < 0.001), indicating
      a better seal. In contrast, the first time success rate for insertion of the
      Baska mask was lower than that seen with the cLMA (52/71 (73%) vs 77/99 (98%),
      respectively, p < 0.001). There were no differences in overall device insertion
      success rates (78/79 (99%) vs 68/71 (96%), respectively, p = 0.54). The Baska
      mask proved more difficult to insert, requiring more insertion attempts, taking
      longer to insert and had higher median (IQR [range]) insertion difficulty scores
      (1.6 (0.8-2.2 [0.1-5.6]) vs 0.5 (0.3-1.4 [0.1-4.0]), respectively, p < 0.001).
      There was also an increased rate of minor blood staining of the Baska mask after
      removal, but there were no differences in other complication rates, such as
      laryngospasm, or in the severity of throat discomfort. In conclusion, in clinical
      situations where the seal with the glottic aperture takes priority over ease of
      insertion, the Baska mask may provide a useful alternative to the cLMA.

PMID- 23855899
TI  - Roughening and long-range nanopatterning of Au(111) through potential cycling in
      aqueous acidic media.
AB  - Electrochemical treatment of Au(111) in aqueous H2SO4 solution by repetitive
      application of oxide formation-reduction cycles (OFRC) generates nanopatterned
      surfaces with long-range order. The pattern development depends on the lower and
      upper potential limits (EL, EU), the number (n) of OFRCs, and the potential scan
      rate (s). Surface patterning of Au(111) initially (n = 1-2) generates small
      islands and holes that are one atomic step in height. As n increases to 5, the
      number of islands decreases and the holes become larger; after n = 10 OFRCs, the
      islands become inexistent and large, randomly distributed holes are observed.
      Increase of OFRCs to n = 20 generates surface structures that reside within three
      atomic layers and resemble phase separation through a spinodal decomposition
      mechanism. As the number of OFRCs rises to n = 50, a network of interconnected
      islands and holes emerges; the islands and holes are two-three atomic steps in
      height, and are located within topmost five monolayers. Further increase of the
      number of OFRCs to n = 100 creates a network of interconnected trigonal pyramids
      that are pointed in the same direction. The size of the pyramids depends on the
      electrolyte composition and the number of OFRCs. In the case of n = 100, the
      pyramids are 12-25 nm in base length and 0.4-1.6 nm in height in 0.1 M aqueous
      H2SO4, and 20-50 nm in base length and 0.8-1.6 nm in height in 0.1 M aqueous
      HNO3. The number of OFRCs and scan rate play an important role in patterning of
      Au(111), and complete nanopattern development requires a large number of OFRCs
      and low scan rates. 

PMID- 23855900
TI  - Prevalent inhibitors in haemophilia B subjects enrolled in the Universal Data
      Collection database.
AB  - Several risk factors for inhibitors have recently been described for haemophilia
      A. It has been assumed that similar risk factors are also relevant for
      haemophilia B, but there is limited data to confirm this notion. The aim of this
      study was to determine the prevalence of and risk factors associated with
      inhibitors in haemophilia B. The database of the Universal Data Collection (UDC)
      project of the Centers for Disease Control for the years 1998-2011 was queried to
      determine the prevalence of inhibitors in haemophilia B subjects. In addition,
      disease severity, race/ethnicity, age, factor exposure and prophylaxis usage were
      evaluated to determine their impact on inhibitor prevalence. Of the 3785 male
      subjects with haemophilia B enrolled in the UDC database, 75 (2%) were determined
      to have an inhibitor at some point during the study period. Severe disease (OR
      13.1, 95% CI 6.2-27.7), black race (OR 2.2, 95% CI 1.2-4.1), and age <11 years
      (OR 2.5, 95% CI 1.5-4.0) were found to be significantly associated with having an
      inhibitor. There was insufficient data to determine if type of factor used and
      prophylaxis were associated with inhibitors. Inhibitors in haemophilia B are much
      less prevalent than haemophilia A, especially in patients with mild disease.
      Similar factors associated with inhibitors in haemophilia A also seem to be
      present for haemophilia B. The information collected by this large surveillance
      project did not permit evaluation of potential risk factors related to treatment
      approaches and exposures, and additional studies will be required.

PMID- 23855901
TI  - A novel dry chemical path way for diene and dienophile surface functionalization
      toward thermally responsive metal-polymer adhesion.
AB  - In this paper, we report a new and easily up-scalable dry chemical method to
      functionalize with diene and dienophile groups a large range of surfaces, such as
      metal, polymer, or glass, and we demonstrate the potentiality of this technique
      to realize thermally responsive adhesion between these materials. A complete and
      extensive surface chemistry analysis of the grafted surfaces, based on the
      deposition of an anhydride-rich thin plasma polymer layer by using an atmospheric
      pressure dielectric barrier discharge (DBD) plasma process, and its subsequent
      gas phase aminolysis reaction with specific diene or dienophile compound is
      discussed. The optimization of the assembling condition for these tailored
      surfaces has led to achieve a Diels-Alder adhesion force up to 0.6 N/mm at
      ambient temperature, which can be reduced by a factor of 50 when the retro Diels
      Alder is ignited at a heating temperature around 200  degrees C. The study of the
      failure interface produced after peeling tests is presented and a mechanism of
      failure is proposed, based on forensic analyses involving surface analytical
      techniques such as XPS, ToF-SIMS, and SEM combined to AFM analyses for the
      retrieving of chemical and morphological information. 

PMID- 23855902
TI  - Small-cell carcinoma of the breast with squamous differentiation.

PMID- 23855903
TI  - Preliminary injunctions in generic and branded patent litigation.

PMID- 23855905
TI  - Benefit of skin ultrasound examination in determining the area of inguinal lymph
      node dissection.

PMID- 23855904
TI  - Widespread acquisition of antimicrobial resistance among Campylobacter isolates
      from UK retail poultry and evidence for clonal expansion of resistant lineages.
AB  - BACKGROUND: Antimicrobial resistance is increasing among clinical Campylobacter
      cases and is common among isolates from other sources, specifically retail
      poultry - a major source of human infection. In this study the antimicrobial
      susceptibility of isolates from a UK-wide survey of Campylobacter in retail
      poultry in 2001 and 2004-5 was investigated. The occurrence of phenotypes
      resistant to tetracycline, quinolones (ciprofloxacin and naladixic acid),
      erythromycin, chloramphenicol and aminoglycosides was quantified. This was
      compared with a phylogeny for these isolates based upon Multi Locus Sequence
      Typing (MLST) to investigate the pattern of antimicrobial resistance acquisition.
      RESULTS: Antimicrobial resistance was present in all lineage clusters, but
      statistical testing showed a non-random distribution. Erythromycin resistance was
      associated with Campylobacter coli. For all antimicrobials tested, resistant
      isolates were distributed among relatively distant lineages indicative of
      widespread acquisition. There was also evidence of clustering of resistance
      phenotypes within lineages; indicative of local expansion of resistant strains.
      CONCLUSIONS: These results are consistent with the widespread acquisition of
      antimicrobial resistance among chicken associated Campylobacter isolates, either
      through mutation or horizontal gene transfer, and the expansion of these lineages
      as a proportion of the population. As Campylobacter are not known to multiply
      outside of the host and long-term carriage in humans is extremely infrequent in
      industrialized countries, the most likely location for the proliferation of
      resistant lineages is in farmed chickens.

PMID- 23855906
TI  - Virus replicon particle based Chikungunya virus neutralization assay using
      Gaussia luciferase as readout.
AB  - BACKGROUND: Chikungunya virus (CHIKV) has been responsible for large epidemic
      outbreaks causing fever, headache, rash and severe arthralgia. So far, no
      specific treatment or vaccine is available. As nucleic acid amplification can
      only be used during the viremic phase of the disease, serological tests like
      neutralization assays are necessary for CHIKV diagnosis and for determination of
      the immune status of a patient. Furthermore, neutralization assays represent a
      useful tool to validate the efficacy of potential vaccines. As CHIKV is a BSL3
      agent, neutralization assays with infectious virus need to be performed under
      BSL3 conditions. Our aim was to develop a neutralization assay based on non
      infectious virus replicon particles (VRPs). METHODS: VRPs were produced by
      cotransfecting baby hamster kidney-21 cells with a CHIKV replicon expressing
      Gaussia luciferase (Gluc) and two helper RNAs expressing the CHIKV capsid protein
      or the remaining structural proteins, respectively. The resulting single round
      infectious particles were used in CHIKV neutralization assays using secreted Gluc
      as readout. RESULTS: Upon cotransfection of a CHIKV replicon expressing Gluc and
      the helper RNAs VRPs could be produced efficiently under optimized conditions at
      32 degrees C. Infection with VRPs could be measured via Gluc secreted into the
      supernatant. The successful use of VRPs in CHIKV neutralization assays was
      demonstrated using a CHIKV neutralizing monoclonal antibody or sera from CHIKV
      infected patients. Comparison of VRP based neutralization assays in 24- versus 96
      well format using different amounts of VRPs revealed that in the 96-well format a
      high multiplicity of infection is favored, while in the 24-well format reliable
      results are also obtained using lower infection rates. Comparison of different
      readout times revealed that evaluation of the neutralization assay is already
      possible at the same day of infection. CONCLUSIONS: A VRP based CHIKV
      neutralization assay using Gluc as readout represents a fast and useful method to
      determine CHIKV neutralizing antibodies without the need of using infectious
      CHIKV.

PMID- 23855907
TI  - EMG-based pattern recognition approach in post stroke robot-aided rehabilitation:
      a feasibility study.
AB  - BACKGROUND: Several studies investigating the use of electromyographic (EMG)
      signals in robot-based stroke neuro-rehabilitation to enhance functional
      recovery. Here we explored whether a classical EMG-based patterns recognition
      approach could be employed to predict patients' intentions while attempting to
      generate goal-directed movements in the horizontal plane. METHODS: Nine right
      handed healthy subjects and seven right-handed stroke survivors performed
      reaching movements in the horizontal plane. EMG signals were recorded and used to
      identify the intended motion direction of the subjects. To this aim, a standard
      pattern recognition algorithm (i.e., Support Vector Machine, SVM) was used.
      Different tests were carried out to understand the role of the inter- and intra
      subjects' variability in affecting classifier accuracy. Abnormal muscular spatial
      patterns generating misclassification were evaluated by means of an assessment
      index calculated from the results achieved with the PCA, i.e., the so-called
      Coefficient of Expressiveness (CoE). RESULTS: Processing the EMG signals of the
      healthy subjects, in most of the cases we were able to build a static functional
      map of the EMG activation patterns for point-to-point reaching movements on the
      horizontal plane. On the contrary, when processing the EMG signals of the
      pathological subjects a good classification was not possible. In particular,
      patients' aimed movement direction was not predictable with sufficient accuracy
      either when using the general map extracted from data of normal subjects and when
      tuning the classifier on the EMG signals recorded from each patient. CONCLUSIONS:
      The experimental findings herein reported show that the use of EMG patterns
      recognition approach might not be practical to decode movement intention in
      subjects with neurological injury such as stroke. Rather than estimate motion
      from EMGs, future scenarios should encourage the utilization of these signals to
      detect and interpret the normal and abnormal muscle patterns and provide feedback
      on their correct recruitment.

PMID- 23855908
TI  - Cyanide-bridged W(V)Mn(III) bimetallic chains composed of a blocked W hexacyanide
      precursor: geometry-related magnetic couplings and magnetostructural correlation.
AB  - Five one-dimensional bimetallic W(V)Mn(III) complexes 1-5, consisting of
      [W(CN)6(bpy)](-) anions and [Mn(Schiff base)](+) cations, were prepared. The
      central coordination geometry around each W atom is determined as a distorted
      dodecahedron (DD) for 1 and 2, and a distorted square antiprism (SAPR) for 3-5.
      Magnetic analyses demonstrate that compounds 1, 4, and 5 exhibit
      antiferromagnetic interactions between magnetic centers, which are different from
      the ferromagnetic couplings in 2 and 3. For the distorted DD geometry, the Mn
      N(ax) (ax = axial) bond length increases when moving from 1 to 2, with the Mn
      N(ax)-C(ax) angle remaining constant. The elongation of the bond length is
      responsible for the reduction in orbital overlap and consequent ferromagnetic
      coupling in 2. In comparison, for 3-5 with the distorted SAPR geometry, given
      that the Mn-N(ax) bond lengths are similar across all the samples, the increase
      in the Mn-N(ax)-C(ax) angles accounts for the enhanced magnetic strength.
      Notably, a correlation between structure and magnetic exchange coupling is
      established for the first time in W(V)Mn(III) bimetallic systems based on the
      [W(CN)6(bpy)](-) precursor.

PMID- 23855909
TI  - Correlation among Streptococcus bovis, endocarditis and septicemia in a patient
      with advanced colon cancer: a case report.
AB  - INTRODUCTION: One of the bacterial agents that has been found to be associated
      with colorectal cancer is Streptococcus bovis, with 13% of infective endocarditis
      cases caused by this pathogenic species. CASE PRESENTATION: We describe the case
      of a 57-year-old Caucasian man with infiltrating and ulcerating metastatic
      adenocarcinoma of the sigmoid colon. The patient was receiving second-line
      chemotherapy treatment and, on the eighth day of the second cycle, he developed a
      grade IV pancytopenia. We diagnosed a severe sepsis with positive blood cultures
      for Streptococcus bovis/gallolyticus with a secondary endocarditis. CONCLUSIONS:
      A recent study suggests that the majority of patients affected by colonic cancer
      have a Streptococcus bovis/gallolyticus colonization that becomes apparent as an
      overt infection only when immunosystem disorders or cardiac valve lesions occur.
      This correlation is important for involving more specialists in a correct and
      early diagnosis of this rare, but potentially fatal, complication.

PMID- 23855910
TI  - An analysis of non-head and neck primaries presenting to the neck lump clinic:
      our experience in two thousand nine hundred and six new patients.

PMID- 23855911
TI  - Use of published research in paediatric nutrition for the scientific
      substantiation of health claims referring to children's development and health.
AB  - The European Food Safety Authority (EFSA) provides policy makers with scientific
      and technical advice in relation to food safety and human nutrition in an
      independent and transparent way, and communicates such advice to the general
      public. Requirements for the scientific substantiation of health claims referring
      to children's development and health are the same as for other health claims.
      However, children (particularly infants) have peculiarities which should be taken
      into account, because these may impair the extrapolation of results to other
      groups. CONCLUSION: Health claims used in commercial communications should be
      authorized only after a scientific assessment of the highest possible standard by
      EFSA. EFSA's negative opinions on rejected claims should not be read as a
      criticism to research studies published in paediatric nutrition but rather
      highlight their limitations in relation to the substantiation of specific health
      claims made on foods.

PMID- 23855912
TI  - Health conceptualization.

PMID- 23855913
TI  - Biosynthetic origins of menisporopsin A.
AB  - Menisporopsin A, produced by Menisporopsis theobromae, shows antimalarial,
      antimycobacterial, and cytotoxic activities. Here, we report the first (13)C
      incorporations at individual carbons of menisporopsin A using sodium [1-(13)C]
      and [2-(13)C] acetate. This result indicates that each of the subunits of the
      pentalactone menisporopsin A is assembled by a polyketide synthase. 

PMID- 23855915
TI  - Dynamics of the job search process: developing and testing a mediated moderation
      model.
AB  - Taking a self-regulatory perspective, we develop a mediated moderation model
      explaining how within-person changes in job search efficacy and chronic
      regulatory focus interactively affect the number of job interview offers and
      whether job search effort mediates the cross-level interactive effects. A sample
      of 184 graduating college students provided monthly reports of their job search
      activities over a period of 8 months. Findings supported the hypothesized
      relationships. Specifically, at the within-person level, job search efficacy was
      positively related with the number of interview offers for job seekers with
      strong prevention focus and negatively related with the number of interview
      offers for job seekers with strong promotion focus. Results show that job search
      effort mediated the moderated relationships. Findings enhance understandings of
      the complex self-regulatory processes underlying job search.

PMID- 23855914
TI  - Relationship between Vitamin D Receptor gene polymorphisms and the components of
      metabolic syndrome.
AB  - BACKGROUND: The Vitamin D Receptor gene (VDR) is expressed in many tissues and
      modulates the expression of several other genes. The purpose of this study was to
      investigate the association between metabolic syndrome (MetSyn) with the presence
      of VDR 2228570 C > T and VDR 1544410 A > G polymorphisms in Brazilian adults.
      METHODS: Two hundred forty three (243) individuals were included in a cross
      sectional study. MetSyn was classified using the criteria proposed by National
      Cholesterol Educational Program--Adult Treatment Panel III. Insulin resistance
      and beta cell secretion were estimated by the mathematical models of HOMA IR and
      beta, respectively. The VDR 2228570 C > T and VDR 1544410 A > G polymorphisms
      were detected by enzymatic digestion and confirmed by allele specific PCR or
      amplification of refractory mutation. RESULTS: Individuals with MetSyn and
      heterozygosis for VDR 2228570 C > T have higher concentrations of iPTH and HOMA
      beta than those without this polymorphism, and subjects with recessive
      homozygosis for the same polymorphisms presented higher insulin resistance than
      those with the heterozygous genotype. There is no association among VDR 1544410 A
      > G and components of MetSyn, HOMA IR and beta, serum vitamin D (25(OH)D3) and
      intact parathormone (iPTH) levels in patients with MetSyn. A significant lower
      concentration of 25(OH)D3 was observed only in individuals without MetSyn in the
      VDR 1544410 A > G genotype. Additionally, individuals without MetSyn and
      heterozygosis for VDR 2228570 C > T presented higher concentration of
      triglycerides and lower HDL than those without this polymorphism. CONCLUSIONS:
      Using two common VDR polymorphism data suggests they may influence insulin
      secretion, insulin resistance an serum HDL-cholesterol in our highly
      heterogeneous population. Whether VDR polymorphism may influence the severity of
      MetSyn component disorder, warrants examination in larger cohorts used for genome
      wide association studies.

PMID- 23855916
TI  - Examining the asymmetrical effects of goal faultlines in groups: a categorization
      elaboration approach.
AB  - The purpose of this study was to use the categorization-elaboration model (CEM)
      to examine the asymmetrical effects of goal faultlines in groups, which are
      present when hypothetical dividing lines are created on the basis of different
      performance goals, splitting the group into subgroups. On the basis of the CEM,
      we expected groups with goal faultlines to exhibit higher levels of creative task
      performance than (a) groups with specific, difficult goals and (b) groups with do
      your-best goals. We expected the benefits of goal faultlines to be due to
      increases in reflective reframing, which occurs when group members build on each
      other's ideas by shifting to alternate frames. However, we expected groups with
      goal faultlines to exhibit lower levels of routine task performance than (a)
      groups with do-your-best goals and (b) groups with specific, difficult goals, due
      to increased perceptions of loafing. Results from 87 groups generally supported
      our hypothesized model. Implications are discussed as well as possible
      limitations and directions for future research.

PMID- 23855917
TI  - Asymmetric copper(I)-catalyzed azide-alkyne cycloaddition to quaternary
      oxindoles.
AB  - We report a highly enantioselective Cu(I)-catalyzed azide-alkyne cycloaddition
      via asymmetric desymmetrization of oxindole-based 1,6-heptadiynes, which
      furnishes quaternary oxindoles bearing a 1,2,3-triazole-containing moiety with 84
      98% ee. 

PMID- 23855918
TI  - Coring-out fistulectomy with a newly designed 'fistulectome' for complicated
      perianal fistulae: a retrospective clinical analysis.
AB  - AIM: Conventional surgery for complex anal fistula (AF) is associated with
      continence disturbance and recurrence. In the hope of reducing these we developed
      a new mechanical device, the 'fistulectome', to excise the entire fistula tract.
      METHOD: Between March 2001 and April 2011, 136 patients underwent surgery for a
      complex AF using the fistulectome. All fistulae were cryptoglandular in origin.
      Five patients were lost to follow up and were excluded from the analysis.
      RESULTS: Of the 131 fistulae, 76 were trans-sphincteric, 14 were suprasphincteric
      and 16 were extrasphincteric. Seven had a horseshoe extension and 18 were
      unclassified. Of the 131, 108 had recurred after conventional fistulotomy
      performed at another centre and 23 were primary. The mean duration of follow up
      was 34.6 months, the mean hospital stay was 5 days and the healing time was 14
      days. Recurrence, flatus incontinence and soiling occurred in 17 (12.9%), four
      (3.5%) and two (1.52%) patients. CONCLUSION: The results of this series suggest
      that coring-out of a fistula using a fistulectome may be a valid treatment for
      complicated anal fistula.

PMID- 23855919
TI  - Highly sensitive SERS detection of Hg2+ ions in aqueous media using gold
      nanoparticles/graphene heterojunctions.
AB  - Gold nanoparticles (AuNPs)/reduced graphene oxide (rGO) heterojunctions were
      synthesized directly on SiO2/Si substrates via a seed-assisted growth process.
      The in situ chemical fabrication strategy has been proven to be quite simple and
      efficient for generating highly active surface-enhanced Raman scattering (SERS)
      substrates due to synergistic enhanced protocol from rGO and AuNPs. The SERS
      substrates with AuNPs/rGO heterojunctions have been utilized for trace analysis
      of mercury(II) ions via thymine-Hg(2+)-thymine coordination. Thereby, very low
      limits of detection, i.e., 0.1 nM or 20 ppt for Hg(2+), can be achieved in
      contrast with some other SERS subsrtates, which suggests that the heterojunctions
      are appropriate as versatile surface-enhanced substrates applied in chemical
      sensing or biosensing. 

PMID- 23855920
TI  - Review of human-animal interactions and their impact on animal productivity and
      welfare.
AB  - Humans and animals are in regular and at times close contact in modern intensive
      farming systems. The quality of human-animal interactions can have a profound
      impact on the productivity and welfare of farm animals. Interactions by humans
      may be neutral, positive or negative in nature. Regular pleasant contact with
      humans may result in desirable alterations in the physiology, behaviour, health
      and productivity of farm animals. On the contrary, animals that were subjected to
      aversive human contact were highly fearful of humans and their growth and
      reproductive performance could be compromised. Farm animals are particularly
      sensitive to human stimulation that occurs early in life, while many systems of
      the animals are still developing. This may have long-lasting impact and could
      possibly modify their genetic potential. The question as to how human contact can
      have a positive impact on responses to stressors, and productivity is not well
      understood. Recent work in our laboratory suggested that pleasant human contact
      may alter ability to tolerate various stressors through enhanced heat shock
      protein (hsp) 70 expression. The induction of hsp is often associated with
      increased tolerance to environmental stressors and disease resistance in animals.
      The attitude and consequent behaviour of stockpeople affect the animals' fear of
      human which eventually influence animals' productivity and welfare. Other than
      attitude and behaviour, technical skills, knowledge, job motivation, commitment
      and job satisfaction are prerequisites for high job performance. 

PMID- 23855921
TI  - Mosquito-borne diseases--a new threat to Europe?

PMID- 23855923
TI  - Covalent attachment of diamondoid phosphonic acid dichlorides to tungsten oxide
      surfaces.
AB  - Diamondoids (nanometer-sized diamond-like hydrocarbons) are a novel class of
      carbon nanomaterials that exhibit negative electron affinity (NEA) and strong
      electron-phonon scattering. Surface-bound diamondoid monolayers exhibit
      monochromatic photoemission, a unique property that makes them ideal electron
      sources for electron-beam lithography and high-resolution electron microscopy.
      However, these applications are limited by the stability of the chemical bonding
      of diamondoids on surfaces. Here we demonstrate the stable covalent attachment of
      diamantane phosphonic dichloride on tungsten/tungsten oxide surfaces. X-ray
      photoelectron spectroscopy (XPS) and Fourier-transform infrared (FTIR)
      spectroscopy revealed that diamondoid-functionalized tungsten oxide films were
      stable up to 300-350  degrees C, a substantial improvement over conventional
      diamondoid thiolate monolayers on gold, which dissociate at 100-200  degrees C.
      Extreme ultraviolet (EUV) light stimulated photoemission from these diamondoid
      phosphonate monolayers exhibited a characteristic monochromatic NEA peak with 0.2
      eV full width at half-maximum (fwhm) at room temperature, showing that the unique
      monochromatization property of diamondoids remained intact after attachment. Our
      results demonstrate that phosphonic dichloride functionality is a promising
      approach for forming stable diamondoid monolayers for elevated temperature and
      high-current applications such as electron emission and coatings in micro/nano
      electromechanical systems (MEMS/NEMS). 

PMID- 23855924
TI  - The mystery of persistent pulmonary hypertension: an idiopathic infantile
      arterial calcification.
AB  - BACKGROUND: Idiopathic infantile arterial calcification (IIAC) is a rare
      autosomal recessive disorder, characterized by wide spread calcifications in
      arterial walls, leading to vaso-occlusive ischaemia of multiple organs. Mortality
      is high, and there is no definitive treatment. CASE PRESENTATION: A male neonate,
      36+5 weeks gestation, 2.81 kg, was admitted to NICU for respiratory distress. At
      one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a
      hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his
      examination was normal. A chest X-ray showed massive cardiomegaly and pulmonary
      oedema. An echocardiogram (ECHO) indicated moderate persistent pulmonary
      hypertension (PPHN) of unclear etiology. A diagnosis of Idiopathic infantile
      arterial calcification was made and a trial of Editronate therapy was given
      without success. CONCLUSION: IIAC is a rare disorder, it should be considered
      whenever a neonate presents with unexplainable cardiac failure, PPHN, echogenic
      vessels on X-ray/ultrasound and, or concentric hypertrophic ventricles on ECHO.
      Serial antenatal ultrasound findings of echogenic cardiac foci should raise the
      suspicion of IIAC. Further studies to determine the long term effects of
      Editronate on vascular calcifications, disease outcome, and other treatment
      options are needed.

PMID- 23855925
TI  - Theraband exercises with music for persons with haemophilia.

PMID- 23855926
TI  - Adult patients with schizophrenia using violence towards their parents: a
      phenomenological study of views and experiences of violence in parent-child
      dyads.
AB  - AIMS: To describe the lived experiences of aggression and violence among patients
      with schizophrenia and their victimized biological parent as the major caregiver
      being aggressed by their child (parent-adult-child dyads), and to gain an
      understanding of the precipitating factors influencing violence. BACKGROUND:
      Child-to-parent violence, particularly in the mentally ill adult child, is
      arguably the most stressful and under-researched issue of family violence.
      Violence in patients with mental illness is most frequently targeted at family
      members, and most often takes place at home. Both patients and their parents'
      experiences of violence are relatively unexplored. DESIGN: Qualitative study
      design. METHODS: Data were collected using individual in-depth interviews between
      August 2010-August 2011 in Taiwan. Purposive sample of 14 hospitalized patients
      with schizophrenia who had aggression and violence in the past year directed
      towards their biological parent of either gender. FINDINGS: Five main themes were
      identified: violence occurring beyond control in a particular situation
      translated into parent and patient's possible endangerment, the repetitive nature
      of violence, distress, ineffective communication, and management of violence and
      help-seeking. Repetitive violent episodes and tension made both the parent and
      patient feel uncontrollable. Parents had a perceived fear of adverse consequences
      such as being punished by receiving more retribution and they also had concerns
      related to their parental responsibility. CONCLUSIONS: Health professionals
      should be aware of the complexity of phenomena and the interplay of factors
      inducing violence. A comprehensive dyadic parent-child intervention is suggested
      for violence prevention.

PMID- 23855927
TI  - The value of visualizing tone of voice.
AB  - Whilst most of us have an innate feeling for tone of voice, it is an elusive
      quality that even phoneticians struggle to describe with sufficient subtlety. For
      people who cannot speak themselves this can have particularly profound
      repercussions. Augmentative communication often involves text-to-speech, a
      technology that only supports a basic choice of prosody based on punctuation.
      Given how inherently difficult it is to talk about more nuanced tone of voice,
      there is a risk that its absence from current devices goes unremarked and
      unchallenged. Looking ahead optimistically to more expressive communication aids,
      their design will need to involve more subtle interactions with tone of voice
      interactions that the people using them can understand and engage with.
      Interaction design can play a role in making tone of voice visible, tangible, and
      accessible. Two projects that have already catalysed interdisciplinary debate in
      this area, Six Speaking Chairs and Speech Hedge, are introduced together with
      responses. A broader role for design is advocated, as a means to opening up
      speech technology research to a wider range of disciplinary perspectives, and
      also to the contributions and influence of people who use it in their everyday
      lives.

PMID- 23855928
TI  - Individual differences in the relationship transition context: links to
      physiological outcomes.
AB  - The identification of relationship-relevant individual differences is central to
      elucidating how relationship experiences differentially impact individuals'
      health. To this end, we highlight the utility of studying the influence of
      individual differences on physiological outcomes (e.g., cortisol reactivity and
      recovery) in the context of normative relationship transitions. We argue that
      relationship transitions, such as falling in love and the process of committing
      to marry one's partner, amplify the influence of individual differences on
      relationship processes and, by extension, on physiological outcomes. Two such
      individual differences are highlighted-namely, relationship-focused processing
      and dependence-and suggestions for future work are provided. 

PMID- 23855929
TI  - Case of a Mongolian child with extensive Mongolian spots in mucopolysaccharidosis
      type VI: identification of a novel mutation in the arylsulfatase B gene.

PMID- 23855930
TI  - Phylogeography and evolutionary history of hepatitis B virus genotype F in
      Brazil.
AB  - BACKGROUND: Hepatitis B virus (HBV) genotype F (HBV/F) is considered to be
      indigenous to the Americas, but its emergence and spread in the continent remain
      unknown. Previously, only two HBV/F complete genome sequences from Brazil were
      available, limiting the contribution of Brazilian isolates to the phylogenetic
      studies of HBV/F. The present study was carried out to assess the proportion and
      geographic distributions of HBV/F subgenotypes in Brazil, to determine the full
      length genomic sequences of HBV/F isolates from different Brazilian geographic
      regions, and to investigate the detailed evolutionary history and phylogeography
      of HBV/F in Brazil. METHODS: Complete HBV/F genomes isolated from 12 Brazilian
      patients, representing the HBV/F subgenotypes circulating in Brazil, were
      sequenced and analyzed together with sequences retrieved from GenBank, using the
      Bayesian coalescent and phylogeographic framework. RESULTS: Phylogenetic analysis
      using all Brazilian HBV/F S-gene sequences available in GenBank showed that
      HBV/F2a is found at higher frequencies countrywide and corresponds to all
      sequences isolated in the Brazilian Amazon Basin. In addition, the evolutionary
      analysis using complete genome sequences estimated an older median ancestral age
      for the Brazilian HBV/F2a compared to the Brazilian HBV/F1b and HBV/F4
      subgenotypes, suggesting that HBV/F2a represents the original native HBV of
      Brazil. The phylogeographic patterns suggested a north-to-south flow of HBV/F2a
      from Venezuela to Brazil, whereas HBV/F1b and HBV/F4 strains appeared to have
      spread from Argentina to Brazil. CONCLUSIONS: This study suggests a plausible
      route of introduction of HBV/F subgenotypes in Brazil and demonstrates the
      usefulness of recently developed computational tools for investigating the
      evolutionary history of HBV.

PMID- 23855932
TI  - Epidermal growth factor receptor: an important target in esophageal cancer.
AB  - INTRODUCTION: Even after complete tumor removal by surgery, the clinical outcomes
      remain poor in patients with advanced esophageal cancer, justifying the need for
      new treatment options. Epidermal growth factor receptor (EGFR) is a molecular
      target for antibody-based therapy in various cancer types, and it may play
      important roles in the development of esophageal cancer. AREAS COVERED: This
      review evaluates the expression, function, and mechanism of EGFR in esophageal
      cancer and analyzes its value for the prognosis and therapy of esophageal cancer.
      Future developments toward the clinical applications of EGFR to cancer treatment
      are also envisaged. EXPERT OPINION: EGFR may function as an ideal therapeutic
      target for esophageal cancer. Further investigation of epidermal growth-factor
      receptor-mediated pathways will push insight into the novel strategies of target
      therapy for esophageal cancer. More clinical trials should be performed to
      promote the success of therapeutic-clinical use of EGFR and its targets in
      esophageal cancer.

PMID- 23855931
TI  - Pseudomonas DING proteins as human transcriptional regulators and HIV-1
      antagonists.
AB  - BACKGROUND: Anti-HIV-1 therapy depends upon multiple agents that target different
      phases of the viral replication cycle. Recent reports indicate that plant and
      human DING proteins are unique in targeting viral gene transcription as the basis
      of their anti-HIV-1 therapy. METHODS: Two cloned DING genes from Pseudomonas were
      transiently expressed in human cells, and effects on NFkappaB-mediated
      transcription, HIV-1 transcription, and HIV-1 production were measured. RESULTS:
      Both DING proteins elevated NFkappaB-mediated transcription. In microglial cells,
      one protein, from P. aeruginosa PA14, suppressed HIV-1 transcription; the other
      protein, from P. fluorescens SBW25, was inactive. The PA14DING protein also
      reduces HIV-1 production in microglial cells. CONCLUSIONS: Structural differences
      between the two DING proteins highlight regions of the PA14DING protein essential
      to the anti-HIV-1 activity, and may guide the design of therapeutic agents.

PMID- 23855933
TI  - Numerous psammoma bodies in cervical cytology of high-grade endocervical
      adenocarcinoma.

PMID- 23855934
TI  - Passive smoking increases pain perception in children undergoing venous
      catheterization.
AB  - AIM: To establish whether there is any association between passive smoking and
      pain perception in children, in the absence of existing studies into possible
      links. METHODS: This single-centre study focused on 100 children - 50 who had
      been exposed to passive smoking and 50 who had not - who were admitted to general
      polyclinics from September 2012 to December 2012 and needed venous
      catheterization. Patients with chronic diseases, neurologic and psychiatric
      illnesses, communication problems and analgesic use in the last 24 h were
      excluded. The passive smoking group had a mean age of 7.3 years (56% male) and
      the nonpassive smoking group had a mean age of 7.7 years (44% male). The main
      study parameter was the Wong-Baker faces pain rating scale (WBFPS) score during
      catheterization. RESULTS: There was a statistically significant difference
      between the pain perceptions of the 100 children studied and smoke exposure. The
      WBFPS scores of the 50 children who were passive smokers were significantly
      higher than the scores of the 50 who were not passive smokers (p = 0.00).
      CONCLUSION: Passive smoking increases pain perception in children during invasive
      medical procedures.

PMID- 23855936
TI  - Revolting bodies, desiring lesbians: an introduction.
AB  - This introduction gives the background to this special issue of the Journal of
      Lesbian Studies that has its origin in the 18th Annual Lesbian Lives Conference
      of 2011. It traces the theme of Revolting Bodies: Desiring Lesbians across the
      ten articles of this collection and gives a brief summary of each. 

PMID- 23855935
TI  - Primary weight maintenance: an observational study exploring candidate variables
      for intervention.
AB  - BACKGROUND: Previous studies have focused on weight maintenance following weight
      loss, i.e. secondary weight maintenance (SWM). The long-term results of SWM have
      been rather modest and it has been suggested that preventing initial weight gain,
      i.e. primary weight maintenance (PWM), may be more successful. Therefore,
      developing a prevention strategy focused on PWM, enabling normal weight or
      overweight individuals to maintain their weight, would be of great interest. The
      aim of this study was to identify attitudes, strategies, and behaviors that are
      predictive of PWM in different age, sex and BMI groups in Northern Sweden.
      METHODS: A questionnaire was mailed to 3497 individuals in a Swedish population
      that had two measured weights taken ten years apart, as participants in the
      Vasterbotten Intervention Programme. Subjects were between 41-63 years of age at
      the time of the survey, had a baseline BMI of 20-30, and a ten year percent
      change in BMI greater than -3%. The respondents were divided into twelve
      subgroups based on baseline age (30, 40 and 50), sex and BMI (normal weight and
      overweight). Analysis of variance (ANOVA), correlation, and linear regression
      were performed to identify independent predictors of PWM. RESULTS: Of the 166
      predictors tested, 152 (91.6%) were predictive of PWM in at least one subgroup.
      However, only 7 of these 152 variables (4.6%) were significant in 6 subgroups or
      more. The number of significant predictors of PWM was higher for male (35.8) than
      female (27.5) subgroups (p=0.044). There was a tendency (non significant) for
      normal weight subgroups to have a higher number of predictors (35.3) than
      overweight subgroups (28.0). Adjusted R-squared values ranged from 0.1 to 0.420.
      CONCLUSIONS: The large number of PWM predictors identified, and accompanying high
      R-squared values, provide a promising first step towards the development of PWM
      interventions. The large disparity in the pattern of significant variables
      between subgroups suggests that these interventions should be tailored to the
      person's demographic (age, sex and BMI). The next steps should be directed
      towards evaluation of these predictors for causal potential.

PMID- 23855937
TI  - The bodies I have lived with: keynote for 18th Lesbian Lives Conference,
      Brighton, England, 2011.
AB  - Nestle pays homage in ideas and images to the bodies, both familial and communal,
      that have informed her life's work-an exploration of the mid-twentieth-century
      American fem-butch community by creating an archive of primary sources, faces and
      words, that challenge prevailing national and sometimes communal narratives of
      what is history and what is absence. 

PMID- 23855938
TI  - Rethinking transgression: disgust, affect, and sexuality in Charlotte Roche's
      Wetlands.
AB  - This article explores the critical reaction to Charlotte Roche's novel Wetlands,
      and considers the ways in which this reaction reflects contemporary thinking on
      sex and transgression. While reviewers position the text as the site of a
      subversive politics and a specifically sexualized form of affect, much of the
      affective power of Wetlands lies less in its treatment of sex than in its largely
      ignored descriptions of the revolting body. Via an analysis of the different
      forms of affect in operation within Wetlands, this article will explore whether
      the association of sex with politically charged subversion may now be subsiding. 

PMID- 23855939
TI  - Remediating politics: brand(ed) new sexualities and real bodies online.
AB  - This article suggests that, in a world emerging in and through mediation, branded
      sex bloggers and portals become (re)mediators of queer and feminist politics. It
      examines the websites of two porn production companies, Nofauxxx and Furry Girl,
      and analyses how they respond to older media forms, re-articulate long-standing
      debates about pornography in new mediated environments, and re-signify the
      pornographic object. Key in this process is the circulation of "authenticity,"
      "real bodies," and "diversity" discourses. Through this circulation, sex
      blogger/brand portals mediate models of queer and feminist political engagement
      entrenched with notions of digital networks and free markets more generally. 

PMID- 23855940
TI  - The revolting Anne Lister: the U.K.'s first modern lesbian.
AB  - Anne Lister has recently been turned from a relatively obscure figure of
      scholarly interest into a modern-day icon of lesbian sexuality. This article asks
      what gesture we perform when we celebrate Lister's life through the lens of
      modernity. Why do we need Lister to be modern, and what does it mean to be so? If
      Lister is recognizable to us as an active and unashamed lesbian subject, is it
      that modernity itself has managed to erase queer shame? Arguably, rather than
      claiming Lister for modernity, perhaps it is Lister who is putting our modernity
      into question. 

PMID- 23855941
TI  - Maria Edgeworth's Angelina, or L'amie Inconnue: queer materiality and the woman
      writer's grotesque body.
AB  - Despite its many similarities to her better-known novel Belinda, Maria
      Edgeworth's Angelina is not usually read as a work about lesbianism--even though
      it begins with the heroine eloping to live with another woman. This article
      explores same-sex relationships in Angelina and suggests reasons for the work's
      comparative neglect by lesbian criticism. It examines the process by which the
      heroine's "unknown friend," the novelist Araminta, moves from being "nobody," a
      textual construct, to a woman all too thoroughly and grotesquely embodied; and it
      discusses the role of queer objects, including literary texts, in that process of
      embodiment.

PMID- 23855942
TI  - Up close and personal: lesbian sub-culture in the female factories of Van
      Diemen's Land.
AB  - This article focuses on how the sexuality of convict women transported in the
      first half of the nineteenth century to Van Diemen's Land (Tasmania) was
      monitored by the British establishment. A series of Victorian enquiries into the
      convict system were set up to report on the efficacy of transportation. I argue
      that the anxious discussion and ensuing policies used to observe, curtail,
      punish, and "correct" convict women's bodies reveal the processes by which
      Victorian gender, class, and race regimes were socially constructed. Further, the
      article argues that convict women used various tools of resistance and defiance,
      one of which was the formation of lesbian sub-cultures as the embodiment of
      sexual dissidence. 

PMID- 23855943
TI  - "Walking and watching" in queer London: Sarah Waters' Tipping The Velvet and The
      Night Watch.
AB  - This article argues that Sarah Waters' representation of London in her historical
      fictions Tipping the Velvet and The Night Watch is used to delineate the gendered
      bodies and sexual identities of her characters. A historical summary demonstrates
      that female masculinity was slowly mapped onto sexual identity between the 1880s
      and 1940s in Britain. The article argues that Waters' "inventive" use of this
      history allows her to question the construction of both historical and
      contemporary identifications. The way that Waters' characters are constricted and
      liberated by London's urban landscape demonstrates the spatial and temporal
      contingency of both gender and sexuality. 

PMID- 23855944
TI  - The queer limits of Pratibha Parmar's Nina's Heavenly Delights.
AB  - This article considers the impossibility and possibilities inherent in discussing
      queerness in films of the South Asian diaspora through the specific lens of
      Scotland. By using the contexts of "impossibility" in describing the same-sex
      desire between South Asian women in two different national contexts, this article
      argues that while same-sex desire becomes "possible" in the Scottish context of
      Parmar's film (conforming to a type of "coming out" story), Mehta's film cannot
      posit any open or stable lesbian subject. In light of this, even though Parmar's
      film may be the more optimistic realization of South Asian lesbian identity, its
      queer potential is shut down by the parameters of a Western coming out story. 

PMID- 23855945
TI  - Women in wetsuits: revolting bodies in lesbian surf culture.
AB  - The article unpicks the notion of lesbian bodies as revolting through an analysis
      of how "women in wetsuits" are experienced as both disgusting and desirable by
      lesbian surfers. Based on ethnographic research carried out within British surf
      culture, I consider how lesbian surfing bodies come to be experienced and
      embodied as disgusting, desirable, and revolting. Informed by interview data and
      personal reflections I suggest that the affective power of lesbian desire might
      offer ways in which to disrupt the cultural processes that shame bodies and in
      doing so enable surfing bodies to revolt. 

PMID- 23855946
TI  - Revolting doubles: radical narcissism and the trope of lesbian doppelgangers.
AB  - This article is concerned with a repositioning of popular culture images and
      narratives that are, and have been, highly unpopular among queer audiences. This
      involves a re-engagement with the visual representation of lesbian lovers as
      doubles, ubiquitous in popular culture. It argues that by positioning the trope
      of the lesbian doppelgangers as it appears in popular culture on a continuum of
      visual representations of sameness and likeness that also includes feminist and
      queer art its qualities of radical or "absolute" narcissism are brought to the
      fore to be enjoyed as a subversive statement of highly self-referencing, auto
      erotic, and self-sufficient economy of desire. In a reading of Black Swan (2010),
      a film that has attracted notable negative responses from feminist critics, it
      discusses how radical narcissism disturbs the heteronormative matrix through a
      refusal of its underpinning organization of desire and identification as
      exclusionary. It closes by engaging with contemporary artworks drawing on the
      doppelganger motif. 

PMID- 23855947
TI  - Bringing gay and lesbian activism to the White House: Midge Costanza and the
      National Gay Task Force Meeting.
AB  - In March 1977, President Carter's Assistant Margaret "Midge" Costanza made
      history by meeting with representatives from the National Gay Task Force (NGTF)
      to hear their grievances about discriminatory federal policies. The effects of
      the meeting were many, including changes in policies of the Bureau of Prisons and
      the Public Health Service. It also initiated policy discussions that would
      continue for decades and contributed to the incorporation of gay rights within
      the Democratic Party. Midge Costanza was fundamental to the process. It was her
      decision to hold the meeting and to advocate on behalf of the NGTF, and she bore
      many of the meeting's political costs. In this article we make use of Costanza's
      own papers and multiple interviews with her to closely analyze Costanza's role in
      the historic meeting. In addition to adding detail to its politics and policy
      impacts of the meeting, we also look at her complex motivations for holding such
      a controversial meeting. Costanza maintained until her death in 2010 that she was
      motivated by her feminism and overall commitment to social justice, rather than
      her own identity or experiences. 

PMID- 23855948
TI  - Researching older lesbians: problems and partial solutions.
AB  - There is a lack of research about older lesbians, who can be considered not only
      a "hidden population" but also a population in hiding. Yet older lesbians hold
      vital historical and cultural narratives that are, in turn, the heritage of
      younger lesbians. They also have much to contribute to understandings about
      gender, sexuality and aging, and to their currently unmet needs in terms of age
      related housing, health, and social care provision. This article reflects on some
      of the issues that make it difficult to access older lesbians for research
      purposes. It identifies four problematic areas in researching older lesbians:
      definitions, access, representative sampling, and ethical issues. It suggests
      that participative action research might offer a means of widening access and
      engaging with older lesbians in a more collaborative way. 

PMID- 23855951
TI  - Acute cardiovascular toxicity of low-dose intrathecal ziconotide.

PMID- 23855953
TI  - Hydrolysis reactions of the taccalonolides reveal structure-activity
      relationships.
AB  - The taccalonolides are microtubule stabilizers isolated from plants of the genus
      Tacca that show potent in vivo antitumor activity and the ability to overcome
      multiple mechanisms of drug resistance. The most potent taccalonolide identified
      to date, AJ, is a semisynthetic product generated from the major plant metabolite
      taccalonolide A in a two-step reaction. The first step involves hydrolysis of
      taccalonolide A to generate taccalonolide B, and then this product is oxidized to
      generate an epoxide group at C-22-C-23. To generate sufficient taccalonolide AJ
      for in vivo antitumor efficacy studies, the hydrolysis conditions for the
      conversion of taccalonolide A to B were optimized. During purification of the
      hydrolysis products, we identified the new taccalonolide AO (1) along with
      taccalonolide I. When the same hydrolysis reaction was performed on a
      taccalonolide E-enriched fraction, four new taccalonolides, assigned as AK, AL,
      AM, and AN (2-5), were obtained in addition to the expected product taccalonolide
      N. Biological assays were performed on each of the purified taccalonolides, which
      allowed for increased refinement of the structure-activity relationship of this
      class of compounds. 

PMID- 23855952
TI  - Aerobic transformation of cadmium through metal sulfide biosynthesis in
      photosynthetic microorganisms.
AB  - BACKGROUND: Cadmium is a non-essential metal that is toxic because of its
      interference with essential metals such as iron, calcium and zinc causing
      numerous detrimental metabolic and cellular effects. The amount of this metal in
      the environment has increased dramatically since the advent of the industrial age
      as a result of mining activities, the use of fertilizers and sewage sludge in
      farming, and discharges from manufacturing activities. The metal bioremediation
      utility of phototrophic microbes has been demonstrated through their ability to
      detoxify Hg(II) into HgS under aerobic conditions. Metal sulfides are generally
      very insoluble and therefore, biologically unavailable. RESULTS: When Cd(II) was
      exposed to cells it was bioconverted into CdS by the green alga Chlamydomonas
      reinhardtii, the red alga Cyanidioschyzon merolae, and the cyanobacterium,
      Synechoccocus leopoliensis. Supplementation of the two eukaryotic algae with
      extra sulfate, but not sulfite or cysteine, increased their cadmium tolerances as
      well as their abilities to produce CdS, indicating an involvement of sulfate
      assimilation in the detoxification process. However, the combined activities of
      extracted serine acetyl-transferase (SAT) and O-acetylserine(thiol)lyase (OASTL)
      used to monitor sulfate assimilation, was not significantly elevated during cell
      treatments that favored sulfide biosynthesis. It is possible that the prolonged
      incubation of the experiments occurring over two days could have compensated for
      the low rates of sulfate assimilation. This was also the case for S. leopoliensis
      where sulfite and cysteine as well as sulfate supplementation enhanced CdS
      synthesis. In general, conditions that increased cadmium sulfide production also
      resulted in elevated cysteine desulfhydrase activities, strongly suggesting that
      cysteine is the direct source of sulfur for CdS synthesis. CONCLUSIONS:
      Cadmium(II) tolerance and CdS formation were significantly enhanced by sulfate
      supplementation, thus indicating that algae and cyanobacteria can produce CdS in
      a manner similar to that of HgS. Significant increases in sulfate assimilation as
      measured by SAT-OASTL activity were not detected. However, the enhanced activity
      of cysteine desulfhydrase indicates that it is instrumental in the provision of
      H2S for aerobic CdS biosynthesis.

PMID- 23855954
TI  - Acute refractory hypoxemia after chest trauma reversed by high-frequency
      oscillatory ventilation: a case report.
AB  - INTRODUCTION: Polytrauma often results in significant hypoxemia secondary to
      direct lung contusion or indirectly through atelectasis, systemic inflammatory
      response, large volume fluid resuscitation and blood product transfusion. In
      addition to causing hypoxemia, atelectasis and acute lung injury can lead to
      right ventricular failure through an acute increase in pulmonary vascular
      resistance. Mechanical ventilation is often applied, accompanied with recruitment
      maneuvers and positive end-expiratory pressure in order to recruit alveoli and
      reverse atelectasis, while preventing excessive alveolar damage. This strategy
      should lead to the reversal of the hypoxemic condition and the detrimental heart
      lung interaction that may occur. However, as described in this case report,
      hemodynamic instability and intractable alveolar atelectasis sometimes do not
      respond to conventional ventilation strategies. CASE PRESENTATION: We describe
      the case of a 21-year-old Caucasian man with severe chest trauma requiring
      surgical interventions, who developed refractory hypoxemia and overt right
      ventricular failure. After multiple failed attempts of recruitment using
      conventional ventilation, the patient was ventilated with high-frequency
      oscillatory ventilation. This mode of ventilation allowed the reversal of the
      hemodynamic effects of severe hypoxemia and of the acute cor pulmonale. We use
      this case report to describe the physiological advantages of high-frequency
      oscillatory ventilation in patients with chest trauma, and formulate the
      arguments to explain the positive effect observed in our patient. CONCLUSIONS:
      High-frequency oscillatory ventilation can be used in the context of a blunt
      chest trauma accompanied by severe hypoxemia due to atelectasis. The positive
      effect is due to its capacity to recruit the collapsed alveoli and, as a result,
      the relief of increased pulmonary vascular resistance and subsequently the
      reversal of acute cor pulmonale. This approach may represent an alternative in
      case of failure of the conventional ventilation strategy.

PMID- 23855955
TI  - An audit of the nature and impact of clinical coding subjectivity variability and
      error in otolaryngology.
AB  - OBJECTIVES: To audit the accuracy of clinical coding in otolaryngology, assess
      the effectiveness of previously implemented interventions, and determine ways in
      which it can be further improved. DESIGN: Prospective clinician-auditor
      multidisciplinary audit of clinical coding accuracy. PARTICIPANTS: Elective and
      emergency ENT admissions and day-case activity. MAIN OUTCOME MEASURES:
      Concordance between initial coding and the clinician-auditor multi-disciplinary
      teams (MDT) coding in respect of primary and secondary diagnoses and procedures,
      health resource groupings health resource groupings (HRGs) and tariffs. RESULTS:
      The audit of 3131 randomly selected otolaryngology patients between 2010 and 2012
      resulted in 420 instances of change to the primary diagnosis (13%) and 417
      changes to the primary procedure (13%). In 1420 cases (44%), there was at least
      one change to the initial coding and 514 (16%) health resource groupings changed.
      There was an income variance of L343,169 or L109.46 per patient. The highest
      rates of health resource groupings change were observed in head and neck surgery
      and in particular skull-based surgery, laryngology and within that tracheostomy,
      and emergency admissions, and specially, epistaxis management. A randomly
      selected sample of 235 patients from the audit were subjected to a second audit
      by a second clinician-auditor multi-disciplinary team. There were 12 further
      health resource groupings changes (5%) and at least one further coding change
      occurred in 57 patients (24%). These changes were significantly lower than those
      observed in the pre-audit sample, but were also significantly greater than zero.
      Asking surgeons to 'code in theatre' and applying these codes without further
      quality assurance to activity resulted in an health resource groupings error rate
      of 45%. The full audit sample was regrouped under health resource groupings 3.5
      and was compared with a previous audit of 1250 patients performed between 2007
      and 2008. This comparison showed a reduction in the baseline rate of health
      resource groupings change from 16% during the first audit cycle to 9% in the
      current audit cycle (P < 0.001). CONCLUSIONS: Otolaryngology coding is complex
      and susceptible to subjectivity, variability and error. Coding variability can be
      improved, but not eliminated through regular education supported by an audit
      programme.

PMID- 23855956
TI  - Catalyst-controlled C-O versus C-N allylic functionalization of terminal olefins.
AB  - The divergent synthesis of syn-1,2-aminoalcohol or syn-1,2-diamine precursors
      from a common terminal olefin has been accomplished using a combination of
      palladium(II) catalysis with Lewis acid cocatalysis. Palladium(II)/bis-sulfoxide
      catalysis with a silver triflate cocatalyst leads for the first time to anti-2
      aminooxazolines (C-O) in good to excellent yields. Simple removal of the bis
      sulfoxide ligand from this reaction results in a complete switch in reactivity to
      afford anti-imidazolidinone products (C-N) in good yields and excellent
      diastereoselectivities. Mechanistic studies suggest the divergent C-O versus C-N
      reactivity from a common ambident nucleophile arises due to a switch in mechanism
      from allylic C-H cleavage/functionalization to olefin isomerization/oxidative
      amination. 

PMID- 23855957
TI  - Robust carboxylic acid-terminated organic thin films and nanoparticle protectants
      generated from bidentate alkanethiols.
AB  - A new carboxylic acid-terminated alkanethiol having bidentate character, 16-(3,5
      bis(mercaptomethyl)phenoxy)hexadecanoic acid (BMPHA), was designed as an
      absorbate and protectant to form thermally stable carboxylic acid-terminated
      organic thin films on flat gold and nanoparticles, respectively. The structural
      features of the organic thin films derived from BMPHA were characterized by
      ellipsometry, X-ray photoelectron spectroscopy (XPS), and polarization modulation
      infrared reflection absorption spectroscopy (PM-IRRAS), and compared to those
      derived from mercaptohexadecanoic acid (MHA) and 16-(4
      (mercaptomethyl)phenoxy)hexadecanoic acid (MMPHA). This study demonstrates that
      films derived from BMPHA are less densely packed than films derived from MHA and
      MMPHA. However, the results of solution-phase thermal desorption tests revealed
      that the carboxylic acid-terminated films generated from BMPHA exhibit an
      enhanced thermal stability compared to those generated from MHA and MMPHA.
      Furthermore, as a nanoparticle protectant, BMPHA can be used to stabilize large
      gold nanoparticles (~45 nm diameter) in solution, and BMPHA-protected gold
      nanoparticles exhibited a high thermal stability in solution thermolysis studies.

PMID- 23855959
TI  - Ni-doped graphene/carbon cryogels and their applications as versatile sorbents
      for water purification.
AB  - Ni-doped graphene/carbon cryogels (NGCC) have been prepared by adding resorcinol
      and formaldehyde to suspension of graphene oxide (GO), using Ni(2+) ions as
      catalysts for the gelation process to substitute the usually used alkaline
      carbonates. The metal ions of Ni(2+) have elevated the cross-linking between GO
      and RF skeletons, thus strengthening the whole cryogel. The as-formed three
      dimensional (3D) interconnected structures, which can be well-maintained after
      freeze-drying of the hydrogel precursor and subsequent carbonization under an
      inert atmosphere, exhibit good mechanical properties. During the carbonization
      process, Ni(2+) ions are converted into Ni nanoparticles and thus embedded in the
      interconnected structures. The unique porosity within the interconnected
      structures endows the cryogels with good capability for the extraction of oils
      and some organic solvents while the bulk form enables its recycling use. When
      ground into powders, they can be used as adsorbents for dyestuffs. Therefore, the
      as-obtained cryogels may find potential applications as versatile candidates for
      the removal of pollutants from water. 

PMID- 23855960
TI  - In vitro responses of neurofibroma fibroblasts, mast cells and Schwann cells
      obtained from patients with neurofibromatosis 1 to 308-nm excimer light and/or
      vitamin D3.
AB  - Fibroblasts, mast cells and Schwann cells were isolated from neurofibromas of
      patients with neurofibromatosis 1, and their responses to 308-nm excimer light
      irradiation and/or vitamin D3 or an analog (tacalcitol; 1,24-dihydroxyvitamin D3
      ) were examined in vitro. Excimer light irradiation (300 mJ/cm(2) ) suppressed
      the growth of all three cell types. Exposure to 10(-7)  mol/L of 1alpha,25(OH)2
      D3 (VD3 ) or tacalcitol suppressed the growth of fibroblasts and mast cells, but
      not Schwann cells. These results suggest that the different neurofibroma cell
      types show different responses to VD3 . A combination of excimer light
      irradiation and VD3 is necessary to suppress the growth of neurofibroma cells in
      vivo. 

PMID- 23855961
TI  - The role of hope and optimism in suicide risk for American Indians/Alaska
      Natives.
AB  - There are some American Indian/Alaska Native communities that exhibit high rates
      of suicide. The interpersonal theory of suicide (Joiner, 2005) posits that lethal
      suicidal behavior is likely preceded by the simultaneous presence of thwarted
      belongingness, perceived burdensomeness, and acquired capability. Past research
      has shown that hope and optimism are negatively related to suicidal ideation,
      some of the constructs in the interpersonal theory of suicide, and suicide risk
      for the general population. This is the first study to investigate hope and
      optimism in relation to suicidal ideation, thwarted belongingness, perceived
      burdensomeness, and acquired capability for American Indians/Alaska Natives.
      Results showed that hope and optimism negatively predicted thwarted
      belongingness, perceived burdensomeness, and suicidal ideation. However, these
      results were not found for acquired capability. Overall, this study suggests that
      higher levels of hope and optimism are associated with lower levels of suicidal
      ideation, thwarted belongingness, and perceived burdensomeness in this American
      Indian/Alaska Native sample. 

PMID- 23855962
TI  - 'I deserve a treat!': justifications for indulgence undermine the translation of
      intentions into action.
AB  - The present research explores how justifications for indulgence influence the
      translation of 'good' intentions into action. Three studies investigated the
      nature of such justifications and their relation to indulgence. Study 1
      identified six ways that people justify indulgence to themselves - that they are
      deserving or curious, that the indulgence is an exception to the norm or can be
      compensated for later, or that the tempting food is available or irresistible.
      Study 2 showed that the use of justifications undermined participants' strong
      (but not weak) intentions to halve their consumption of a nominated high-fat
      food. Study 3 found that priming the use of justifications increased the amount
      of chocolate that participants consumed in a subsequent, ostensibly unrelated,
      taste test. Again, justification use had a greater effect on participants with
      strong intentions to limit indulgence. Taken together, the studies suggest a new
      approach to understanding intention-behaviour discrepancies. 

PMID- 23855958
TI  - Genetic influences on adolescent sexual behavior: Why genes matter for
      environmentally oriented researchers.
AB  - There are dramatic individual differences among adolescents in how and when they
      become sexually active adults, and early sexual activity is frequently cited as a
      cause of concern for scientists, policymakers, and the general public.
      Understanding the causes and developmental impact of adolescent sexual activity
      can be furthered by considering genes as a source of individual differences.
      Quantitative behavioral genetics (i.e., twin and family studies) and candidate
      gene association studies now provide clear evidence for the genetic underpinnings
      of individual differences in adolescent sexual behavior and related phenotypes.
      Genetic influences on sexual behavior may operate through a variety of direct and
      indirect mechanisms, including pubertal development, testosterone levels, and
      dopaminergic systems. Genetic differences may be systematically associated with
      exposure to environments that are commonly treated as causes of sexual behavior
      (gene-environment correlation). Possible gene-environment correlations pose a
      serious challenge for interpreting the results of much behavioral research.
      Multivariate, genetically informed research on adolescent sexual behavior
      compares twins and family members as a form of quasi experiment: How do twins who
      differ in their sexual experiences differ in their later development? The small
      but growing body of genetically informed research has already challenged dominant
      assumptions regarding the etiology and sequelae of adolescent sexual behavior,
      with some studies indicating possible positive effects of teenage sexuality.
      Studies of Gene * Environment interaction may further elucidate the mechanisms by
      which genes and environments combine to shape the development of sexual behavior
      and its psychosocial consequences. Overall, the existence of heritable variation
      in adolescent sexual behavior has profound implications for environmentally
      oriented theory and research.

PMID- 23855963
TI  - A multidisciplinary quality improvement educational initiative to improve the
      rate of deep-vein thrombosis prophylaxis.
AB  - PURPOSE: To describe a quality improvement initiative to improve deep-vein
      thrombosis (DVT) prophylaxis rates among hospitalized medicine patients. METHODS:
      A standardized admission order-set with an embedded risk-assessment tool and DVT
      prophylaxis orders was developed. RESULTS: An audit 2 months after the
      intervention showed the use of optimal DVT prophylaxis was 91%, an increase from
      75%. Chart review 1 year after the implementation of the order-set revealed that
      the increase in DVT prophylaxis was sustained at 95%. CONCLUSION: The use of
      formalized quality improvement methods to implement an intervention is effective
      in changing physician behaviour.

PMID- 23855964
TI  - Ratio of mutated versus wild-type coat protein sequences in Pepino mosaic virus
      determines the nature and severity of yellowing symptoms on tomato plants.
AB  - Recently, Pepino mosaic virus (PepMV) infections causing severe yellowing
      symptoms in tomato plants have been reported in glasshouse tomato crops. When
      studying this phenomenon in commercial glasshouses, two different types of
      yellowing symptoms, occurring in adjacent plants, were distinguished: interveinal
      leaf yellowing and yellow mosaics. After several weeks, the interveinal leaf
      yellowing symptoms gradually disappeared and the plant heads became green again,
      with yellow mosaic patterns on the leaves as an intermediate stage. The
      sequencing of multiple isolates causing interveinal leaf yellowing identified two
      point mutations, occurring in positions 155 and 166 of the coat protein (CP), as
      unique to the yellowing pathotype. Site-directed mutagenesis of infectious clones
      confirmed that both CP mutations are determinants of the interveinal leaf
      yellowing symptoms. Sequencing of CP clones from plants or plant parts with the
      yellow mosaic symptoms resulted in a mixture of wild-type and mutated sequences,
      whereas sequencing of CP clones from the green heads of recovered plants resulted
      in only wild-type sequences. Yellow mosaic symptoms could be reproduced by
      inoculation of an artificial 1:1 mixture of RNA transcripts from the wild-type
      and mutated infectious clones. These results show that the ratio of mutated
      versus wild-type sequences can determine the nature and severity of symptom
      development. The gradual recovery of the plants, which coincides with the
      disappearance of the yellowing mutations, suggests that selection pressure acts
      to the advantage of the wild-type virus. Experiments with wild-type and mutated
      infectious clones showed that reverse mutation events from mutant to wild-type
      occur and that the wild-type virus does not have a replicative advantage over the
      mutant. These results suggest that reverse mutation events occur, with subsequent
      selection pressure acting in favour of the wild-type virus in the growing plant
      parts, possibly related to a lower long-distance movement efficiency of the
      mutant. 

PMID- 23855965
TI  - Optimization of macroelement concentrations, pH and osmolarity for
      triacylglycerol accumulation in Rhodococcus opacus strain PD630.
AB  - The refinement of biodiesel or renewable diesel from bacterial lipids has a great
      potential to make a contribution for energy production in the future. This study
      provides new data concerning suitable nutrient concentrations for cultivation of
      the Gram-positive Rhodococcus opacus PD630, which is able to accumulate large
      amounts of lipids during nitrogen limitation. Enhanced concentrations of
      magnesium have been shown to increase the final optical density and the lipid
      content of the cells. Elevated phosphate concentrations slowed down the onset of
      the accumulation phase, without a clear effect on the final optical density and
      the cell's lipid content. A robust growth of R. opacus was possible in the
      presence of ammonium concentrations of up to 1.4 g l(-1) and sucrose
      concentrations of up to 240 g l(-1), with an optimum regarding growth and lipid
      storage observed in the range of 0.2 to 0.4 g l(-1) ammonium and 20 to 40 g l(-1)
      sucrose, respectively. Moreover, R. opacus showed tolerance to high salt
      concentrations. 

PMID- 23855967
TI  - Highly efficient, color-pure, color-stable blue quantum dot light-emitting
      devices.
AB  - For colloidal quantum dot light-emitting diodes (QD-LEDs), blue emissive device
      has always been inferior to green and red counterparts with respect to device
      efficiency, primarily because blue QDs possess inherently unfavorable energy
      levels relative to green and red ones, rendering hole injection to blue QDs from
      neighboring hole transport layer (HTL) inefficient. Herein, unprecedented
      synthesis of blue CdZnS/ZnS core/shell QDs that exhibit an exceptional
      photoluminescence (PL) quantum yield of 98%, extraordinarily large size of 11.5
      nm with a shell thickness of 2.6 nm, and high stability against a repeated
      purification process is reported. All-solution-processed, multilayered blue QD
      LEDs, consisting of an HTL of poly(9-vinlycarbazole), emissive layer of CdZnS/ZnS
      QDs, and electron transport layer of ZnO nanoparticles, are fabricated. Our best
      device displays not only a maximum luminance of 2624 cd/m(2), luminous efficiency
      of 2.2 cd/A, and external quantum efficiency of 7.1%, but also no red-shift and
      broadening in electroluminescence (EL) spectra with increasing voltage as well as
      a spectral match between PL and EL. 

PMID- 23855966
TI  - A diet based on multiple functional concepts improves cognitive performance in
      healthy subjects.
AB  - BACKGROUND: Disorders such as the metabolic syndrome (MetS), impaired glucose
      tolerance and diabetes, are associated with increased risk of cognitive decline.
      Also several of the individual key features that define the MetS, e.g.
      hypertension, impaired glucose regulation, dyslipidemia, obesity, and
      inflammation, are related to an increased risk of cognitive decline.
      Consequently, a diet that prevents metabolic disorders might be expected to
      prevent cognitive decline. The purpose of the present study was to, in overweight
      but otherwise healthy subjects, investigate effects on cognitive functions of a
      dietary regime combining multiple functional concepts potentially beneficial to
      risk markers associated with MetS. The purpose was in addition to evaluate
      cognitive performance in relation to results on cardiometabolic risk variables
      (BMI, blood pressure, glucose, insulin, cholesterol, triglycerides, free fatty
      acids, lipoprotein A-1 and B, hs-CRP, HbA1c, interleukin-6, TNF-alpha, and PAI
      1). METHODS: Fourty-four healthy women and men (50-73 years, BMI 25-33, fasting
      glycemia <= 6.1 mmol/L) participated in a randomized, controlled crossover
      intervention, comparing a multifunctional diet (active diet (AD)) including foods
      with a potential anti-inflammatory action, with a control diet (CD) devoid of the
      "active" components. Both diets were composed in close agreement with the Nordic
      dietary recommendations. Each diet was consumed during 4 wk, separated by a 4 wk
      washout period. Cognitive tests were performed at fasting and in the postprandial
      period after a standardized breakfast, after each diet period. RESULTS: In
      comparison with the CD, the AD improved performance in the Rey Auditory-Verbal
      Learning test (recognition test, p < 0.05, ANOVA, n = 42) and significantly
      improved performance in test of selective attention, which also included aspects
      of working memory (p < 0.05, n = 40). Performance in cognitive tests was
      inversely associated with plasma concentrations of cardiometabolic risk markers
      (fasting cholesterol, blood glucose, blood pressure) and cardiovascular risk
      scores (Framingham and Reynols), and positivly associated with apolipoprotein A1
      (p < 0.05). CONCLUSIONS: The results indicate that diet characteristics may
      modulate cognitive performance. A relationship seems to exist between
      cardiometabolic risk markers and cognitive performance in apparently healthy
      subjects. The results provide additional motives for diet based prevention of
      metabolic disturbances related to the MetS.

PMID- 23855968
TI  - Charged aerosol detection to characterize components of dispersed-phase
      formulations.
AB  - Colloidal formulations based on biocompatible phospholipids, emulsifiers, and
      oils are employed in a wide range of applications including medicine, food, and
      cosmetics. However, characterization of these dispersed-phase components may be
      difficult to analyze by traditional HPLC with UV, visible, or fluorescence
      detection modalities due to lack of chromophores or fluorophores. Charged aerosol
      detection (CAD) is increasingly used for analysis of dispersed-phase components
      due to its broad applicability and high sensitivity for non-chromophore
      containing components found in many colloidal systems, such as lipid-based
      molecules. In this review, we summarize the recent applications of CAD reported
      in the literature as well as our own laboratory for the analysis of widely used
      components of dispersed-phase systems. In particular, we discuss the advantages
      and disadvantages of CAD compared to other HPLC detection methods, as well as the
      various sample preparation methods suitable for colloidal formulations prior to
      HPLC-CAD analysis. 

PMID- 23855969
TI  - Designing first-in-human dose of coagulation factors: application of
      pharmacokinetic allometric scaling.
AB  - The objectives of this study were to (i) evaluate the predictive performance of
      pharmacokinetic interspecies scaling of coagulation factors to predict clearance
      (CL) and (ii) project first-in-human dose based on the predicted human CL. Human
      CL of nine coagulation factors was predicted using two or three animal species
      using two methods: (i) CL vs. body weight (simple allometry) and where applicable
      (ii) the product of CL and brain weight vs. body weight. Based on the predicted
      human CL, four methods were used to project the first-in-human dose. The
      predicted pharmacokinetic parameters and the estimated first-in-human dose of
      coagulation factors were compared with the observed human values obtained from
      clinical trials. The results of the study indicated that the CL of coagulation
      factors can be predicted with reasonable accuracy in humans and a good estimate
      of first-in-human dose can be obtained from the predicted human CL. The suggested
      methods in this study are not only time and cost-effective but also provide
      rational alternatives to the somewhat arbitrary dose selection process for
      coagulation factors often used. 

PMID- 23855970
TI  - Outcomes of Latina women in CenteringPregnancy group prenatal care compared with
      individual prenatal care.
AB  - INTRODUCTION: CenteringPregnancy is a client-centered model of group prenatal
      care that brings women together into small groups to receive care through
      assessment, education, and support. As Spanish-speaking CenteringPregnancy groups
      become more common, outcomes of Latinas who attend these groups must be assessed.
      The purpose of this retrospective cohort study was to compare pregnancy outcomes
      of Latina women who completed CenteringPregnancy in a public health clinic with
      women who completed individual care in the same clinic during the same time.
      METHODS: Medical charts were reviewed retrospectively to examine differences in
      pregnancy outcomes and maternal factors in both prenatal care groups. Latina
      Spanish-speaking women who completed CenteringPregnancy were matched with Latina
      Spanish-speaking women who completed individual care within the same time frame.
      Logistic regression analysis was conducted to examine maternal and birth
      outcomes. RESULTS: A total of 487 patient charts were obtained for data
      collection (CenteringPregnancy n = 247, individual n = 240). No differences in
      low-birth-weight or preterm births were observed between the groups. Compared
      with women in individual care, women in CenteringPregnancy had higher odds of
      giving birth vaginally (adjusted odds ratio [aOR], 2.57; 95% confidence interval
      [CI], 1.23-5.36), attending prenatal care visits (aOR, 11.03; 95% CI, 4.53
      26.83), attending postpartum care visits (aOR, 2.20; 95% CI, 1.20-4.05), and
      feeding their infants formula only (aOR, 6.07; 95% CI, 2.57-14.3). Women in
      CenteringPregnancy also had lower odds of gaining below the recommended amount of
      gestational weight (aOR, 0.41; 95% CI, 0.22-0.78). DISCUSSION: Women in
      CenteringPregnancy had higher health care utilization, but there were no
      differences in preterm birth or low birth weight. Randomized studies are needed
      to eliminate selection bias.

PMID- 23855971
TI  - Nutrient intakes independently affect growth in extremely preterm infants:
      results from a population-based study.
AB  - AIM: To explore associations between energy and macronutrient intakes and early
      growth in extremely low gestational age (ELGA) infants. METHODS: Retrospective
      population-based study of all ELGA infants (<27 weeks) born in Sweden during 2004
      2007. Detailed data on nutrition and anthropometric measurements from birth to 70
      days of postnatal age were retrieved from hospital records. RESULTS: Study
      infants (n = 531) had a mean +/- SD gestational age of 25.3 +/- 1.1 weeks and a
      birth weight of 765 +/- 170 g. Between 0 and 70 days, average daily energy and
      protein intakes were 120 +/- 11 kcal/kg and 3.2 +/- 0.4 g/kg, respectively.
      During this period, standard deviation scores for weight, length and head
      circumference decreased by 1.4, 2.3 and 0.7, respectively. Taking gestational
      age, baseline anthropometrics and severity of illness into account, lower energy
      intake correlated with lower gain in weight (r = +0.315, p < 0.001), length (r =
      +0.215, p < 0.001) and head circumference (r = +0.218, p < 0.001). Protein intake
      predicted growth in all anthropometric outcomes, and fat intake was positively
      associated with head circumference growth. CONCLUSION: Extremely low gestational
      age infants received considerably less energy and protein than recommended and
      showed postnatal growth failure. Nutrient intakes were independent predictors of
      growth even after adjusting for severity of illness. These findings suggest that
      optimized energy and macronutrient intakes may prevent early growth failure in
      these infants.

PMID- 23855972
TI  - Three distinct mutational mechanisms acting on a single gene underpin the origin
      of yellow flesh in peach.
AB  - Peach flesh color (white or yellow) is among the most popular commercial criteria
      for peach classification, and has implications for consumer acceptance and fruit
      nutritional quality. Despite the increasing interest in improving cultivars of
      both flesh types, little is known about the genetic basis for the carotenoid
      content diversity in peach. Here we describe the association between genotypes at
      a locus encoding the carotenoid cleavage dioxygenase 4 (PpCCD4), localized in
      pseudomolecule 1 of the Prunus persica reference genome sequence, and the flesh
      color for 37 peach varieties, including two somatic revertants, and three
      ancestral relatives of peach, providing definitive evidence that this locus is
      responsible for flesh color phenotype. We show that yellow peach alleles have
      arisen from various ancestral haplotypes by at least three independent mutational
      events involving nucleotide substitutions, small insertions and transposable
      element insertions, and that these mutations, despite being located within the
      transcribed portion of the gene, also result in marked differences in transcript
      levels, presumably as a consequence of differential transcript stability
      involving nonsense-mediated mRNA decay. The PpCCD4 gene provides a unique example
      of a gene for which humans, in their quest to diversify phenotypic appearance and
      qualitative characteristics of a fruit, have been able to select and exploit
      multiple mutations resulting from a variety of mechanisms. 

PMID- 23855974
TI  - Biomechanical simulation of high-heeled shoe donning and walking.
AB  - Footwear serves to protect the foot in various activities, to enhance athletic
      performance in sports and in many cases to fulfill aesthetic and cultural needs
      of urban society. Most women like wearing high-heeled shoes (HHS) for the benefit
      of sensuous attractiveness, while foot problems are often associated.
      Computational modeling based on finite element (FE) analysis is a useful tool for
      deep understanding of foot and footwear biomechanics and incorporating footwear
      with foot in the model is the prerequisite. In this study, a three-dimensional FE
      model of coupled foot-ankle-shoe complex and preceding gait simulation were
      established. Interfacial contact simulation was employed to complete the donning
      process of foot and shoe upper contact. Three major stance phases namely heel
      strike, midstance and push off were simulated to investigate the biomechanical
      response of high-heeled shod walking. It was found that the contact pressure at
      all metatarsophalangeal (MTP) joints intensified and reached their maximum at
      push off phase during locomotion, meanwhile the first MTP had the largest
      magnitude. The first and fifth MTP joints had larger movements in transverse
      plane among all MTP joints, indicating that these two joints bended more
      significantly by toe box restraint during locomotion. The dorsal contact pressure
      at the first toe increased by four times from heel strike to push off. The
      established HHS donning and walking simulation in this study proved the
      versatility and promising potential of computational approach for realistic
      biomechanical evaluation and optimization of footwear design in a virtual
      environment. 

PMID- 23855973
TI  - Eicosapentaenoic and docosahexaenoic acid supplementation and inflammatory gene
      expression in the duodenum of obese patients with type 2 diabetes.
AB  - BACKGROUND: The extent to which long-chain omega-3 polyunsaturated fatty acids
      (LCn-3PUFA) from fish oil such as eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA) exert their anti-inflammatory effects by down-regulating intestinal
      inflammation in humans is unknown. We investigated the impact of LCn-3PUFA
      supplementation on inflammatory gene expression in the duodenum of obese patients
      with type 2 diabetes. FINDINGS: This placebo-controlled randomized crossover
      study included 12 men with type 2 diabetes. After a 4-week run-in period,
      patients received in a random sequence 5 g/d of fish oil (providing 3 g of EPA +
      DHA) and a placebo (corn and soybean oil) for 8 weeks each. The two treatment
      phases were separated by a 12-week washout period. Gene expression was assessed
      by real-time polymerase chain reaction in duodenal biopsy samples obtained in the
      fasted state at the end of each treatment phase. Intestinal mRNA expression
      levels of interleukin (IL)-6 and tumor-necrosis factor (TNF)-alpha were hardly
      detectable after either treatment (<100 copies/105 copies of the reference gene
      ATP5o). Intestinal mRNA expression of IL-18 and of the transcription factor
      signal transducer and activator of transcription 3 (STAT3) was higher (>5000
      copies/105 copies ATP5o) but still relatively low. EPA + DHA supplementation had
      no impact on any of these levels (all P >= 0.73). CONCLUSIONS: These data suggest
      that duodenal cells gene expression of pro-inflammatory cytokines is low in
      patients with type 2 diabetes and not affected by EPA + DHA supplementation.
      Further studies are warranted to determine if inflammatory gene expression in
      other tissues surrounding the intestine is modulated by EPA + DHA
      supplementation. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01449773.

PMID- 23855975
TI  - A case of eosinophilic esophagitis discovered with positron emission tomography
      imaging: a case report.
AB  - INTRODUCTION: Eosinophilic esophagitis was first reported in 1978, and since then
      it has been increasingly recognized as one of the major etiologies for dysphagia,
      food impaction, and food regurgitation. To the best of our knowledge, no case of
      eosinophilic esophagitis (excluding esophageal eosinophilia not responsive to
      proton pump inhibitor treatment) has previously been demonstrated on the basis of
      positron emission tomography imaging. CASE PRESENTATION: A 68-year-old Caucasian
      man presented with dysphagia to solids with recurrent regurgitation and weight
      loss of 7lb within the preceding 2 months. The patient attributed these symptoms
      to radiation therapy he had received 1 year earlier for squamous cell cancer of
      the lung. The patient underwent routine follow-up positron emission tomography
      imaging, which showed a hypermetabolic lesion in the posterior mediastinum and
      was increased at the level of the midesophagus. CONCLUSION: To the best of our
      knowledge, this is the first reported case of eosinophilic esophagitis
      demonstrated by positron emission tomography imaging and confirmed with
      endoscopic evaluation and biopsies both after positron emission tomography
      imaging and a trial of proton pump inhibitor therapy. This could have an impact
      on the diagnostic evaluation of esophageal eosinophilic inflammation as well as
      eosinophilic infiltration of other gastrointestinal organs.

PMID- 23855976
TI  - Photoselective DNA hairpin spin switches.
AB  - DNA hairpins having both a tethered anthraquinone (Aq) end-capping group and a
      perylenediimide (PDI) base surrogate were synthesized, wherein Aq and PDI are
      each separated from a G-C base pair hole trap by A-T and I-C base pairs (G =
      guanine, A = adenine, T= thymine, C = cytosine, I = inosine). Selective
      photoexcitation of PDI at 532 nm generates a singlet radical ion pair (RP),
      (1)(G(+*)-PDI(-*)), while selective photoexcitation of Aq at 355 nm generates the
      corresponding triplet RP, (3)(G(+*)-Aq(-*)). Subsequent radical pair intersystem
      crossing within these spin-correlated RPs leads to mixed spin states that exhibit
      spin-polarized, time-resolved EPR spectra in which the singlet- and triplet
      initiated RPs have opposite phases. These results demonstrate that a carefully
      designed DNA hairpin can serve as a photodriven molecular spin switch based on
      wavelength-selective formation of the singlet or triplet RP without significant
      competition from undesired energy transfer processes. 

PMID- 23855977
TI  - KHA-CARI Guideline: vascular access - central venous catheters, arteriovenous
      fistulae and arteriovenous grafts.

PMID- 23855978
TI  - Why are psychological evaluation and preparation necessary for the patient
      candidate to bariatric surgery?

PMID- 23855979
TI  - Substantial effects of apolipoprotein E epsilon4 on memory decline in very old
      age: longitudinal findings from a population-based sample.
AB  - We examined associations between the apolipoprotein E (APOE) epsilon4 allele and
      levels of performance and rates of change in cognition in late life taking
      incident dementia into account. The sample consisted of 482 nondemented
      individuals, aged 80 years and older at baseline, drawn from the OCTO twin study.
      A battery of 10 cognitive tests was administered at 5 occasions with measurements
      intervals of 2 years. We fitted hierarchical linear models with time specified as
      time to death and controlled for baseline age, sex, education, stroke,
      cardiovascular disease, hypertension, diabetes, and incident dementia. The
      epsilon4 allele was significantly associated with lower levels of performance or
      steeper rate of decline in all 7 memory tests. Largest effect sizes were found in
      tests of delayed recall and recognition memory. The effects of the APOE epsilon4
      allele were, however, reduced to a nonsignificant level in all tests except 1
      after accounting for incident dementia. The findings support the notion that the
      APOE epsilon4 allele is associated with substantial memory decline in very old
      age, but as expected, the effect is largely related to incident dementia. 

PMID- 23855980
TI  - Suppression of central chemokine fractalkine receptor signaling alleviates
      amyloid-induced memory deficiency.
AB  - The abnormal accumulation of amyloid fibrils in the brain is pathognomonic of
      Alzheimer's disease. Amyloid fibrils induce significant neuroinflammation
      characterized by the activation of microglia and impairment of synaptic
      plasticity in the brain that eventually leads to cognitive decline. Chemokine
      fractalkine receptor (CX3CR1) is primarily located in the microglia in the brain
      and its role in the amyloid fibril-induced neuroinflammation and memory
      deficiency remains debated. We found that bilateral microinjection of amyloid
      beta (Abeta)1-40 fibrils into the hippocampal CA1 area of rats resulted in
      significant upregulation of CX3CR1 messenger RNA (mRNA) and protein expression
      (via increasing histone H3 acetylation in the Cx3cr1 promoter region), synaptic
      dysfunction, and cognitive impairment, compared with the control group.
      Suppressing CX3CR1 signaling with CX3CR1 small interfering RNA in rats injected
      with Abeta1-40 fibrils blunted Abeta1-40-induced CX3CR1 upregulation, microglial
      activation, interleukin-1beta expression, restored basal glutamatergic strength
      and electric stimuli-induced long-term potentiation, and cognitive capacities.
      These findings suggest that activation of CX3CR1 plays an important role in the
      neuroinflammatory response and Abeta-induced neuroinflammation and neurotoxicity.

PMID- 23855981
TI  - New role of silent information regulator 1 in cerebral ischemia.
AB  - Silent information regulator 1 (SIRT1) is a type of histone deacetylase whose
      activity is dependent on nicotinamide adenine dinucleotide. SIRT1 plays a key
      role in the longevity effects elicited by calorie restriction. Recently, a
      neuroprotective effect of SIRT1 was reported for neurological diseases. The focus
      of this review is to summarize the protective effects of SIRT1 in cerebral
      ischemia. First, the posttranslational modifications of SIRT1 are illustrated;
      then, we discuss the roles of SIRT1 in cerebral immune homeostasis. Next, we
      introduce the deacetylase activity of SIRT1 in cerebral ischemia and provide some
      examples of relevant studies. In addition, we discuss several activated mediators
      of SIRT1, such as resveratrol, caloric restriction, ischemic preconditioning, and
      other proteins and compounds. Finally, we highlight a few SIRT1-related signaling
      pathways, such as the peroxisome proliferator-activated receptor gamma
      coactivator 1alpha, nuclear transcription factor kappaB, uncoupling protein 2,
      and forkhead box O pathways. Taken together, the information compiled in this
      article will serve as a comprehensive reference for the actions of SIRT1 in the
      nervous system and will help in the design of future experimental research and
      promote SIRT1 as a new therapeutic target. 

PMID- 23855982
TI  - Assessment of TREM2 rs75932628 association with Alzheimer's disease in a
      population-based sample: the Cache County Study.
AB  - Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an
      Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to
      5.1. The Cache County Memory Study is a large, population-based sample designed
      for the study of memory and aging. We genotyped R47H in 2974 samples (427 cases
      and 2540 control subjects) from the Cache County study using a custom TaqMan
      assay. We observed 7 heterozygous cases and 12 heterozygous control subjects with
      an odds ratio of 3.5 (95% confidence interval, 1.3-8.8; p = 0.0076). The minor
      allele frequency and population attributable fraction for R47H were 0.0029 and
      0.004, respectively. This study replicates the association between R47H and
      Alzheimer's disease risk in a large, population-based sample, and estimates the
      population frequency and attributable risk of this rare variant. 

PMID- 23855983
TI  - Inhibition of amyloid beta-induced synaptotoxicity by a pentapeptide derived from
      the glycine zipper region of the neurotoxic peptide.
AB  - A major characteristic of Alzheimer's disease is the presence of amyloid beta
      (Abeta) oligomers and aggregates in the brain. Abeta oligomers interact with the
      neuronal membrane inducing perforations, causing an influx of calcium ions and
      increasing the release of synaptic vesicles that leads to a delayed synaptic
      failure by vesicle depletion. Here, we identified a neuroprotective pentapeptide
      anti-Abeta compound having the sequence of the glycine zipper region of the C
      terminal of Abeta (G33LMVG37). Docking and Forster resonance energy transfer
      experiments showed that G33LMVG37 interacts with Abeta at the C-terminal region,
      which is important for Abeta association and insertion into the lipid membrane.
      Furthermore, this pentapeptide interfered with Abeta aggregation, association,
      and perforation of the plasma membrane. The synaptotoxicity induced by Abeta
      after acute and chronic applications were abolished by G33LMVG37. These results
      provide a novel rationale for drug development against Alzheimer's disease. 

PMID- 23855985
TI  - Theoretical simulations of structure and X-ray photoelectron spectra of glycine
      and diglycine adsorbed on Cu(110).
AB  - The study of adsorption of glycine and glycylglycine (or diglycine) on a copper
      surface is an important step for the comprehension of mechanisms that determine
      the stability of biological functionalizers on metal substrates. These two
      molecules can be considered as prototypes and essential models to investigate,
      theoretically and experimentally, the adaptability of flexible short peptide
      chains to a definite interface. In this work, we have improved and updated
      earlier molecular dynamics simulations by including reactivity of the various
      species and the comparison of ab initio calculated C, N, and O core photoelectron
      chemical shifts with the ones found in previous studies. New diglycine-copper
      bonding is predicted, and the results of the chemical shift analysis are, in all
      cases, fully compatible with structural information obtained through experimental
      measurements. Moreover, we have found that the process of proton transfer, which
      is fundamental in the dynamics of amino acids and peptides, occurs mainly by
      intermolecular interaction between the first and second layer of the adsorbate. 

PMID- 23855984
TI  - Insights into TREM2 biology by network analysis of human brain gene expression
      data.
AB  - Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease.
      Here we use microarray-based expression data generated from 101
      neuropathologically normal individuals and covering 10 brain regions, including
      the hippocampus, to understand TREM2 biology in human brain. Using network
      analysis, we detect a highly preserved TREM2-containing module in human brain,
      show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5
      brain regions, including the hippocampus, suggesting that it can drive module
      function. Using enrichment analysis we show significant overrepresentation of
      genes implicated in the adaptive and innate immune system. Inspection of genes
      with the highest connectivity to TREM2 suggests that it plays a key role in
      mediating changes in the microglial cytoskeleton necessary not only for
      phagocytosis, but also migration. Most importantly, we show that the TREM2
      containing module is significantly enriched for genes genetically implicated in
      Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that
      these diseases share common pathways centered on microglia and that among the
      genes identified are possible new disease-relevant genes. 

PMID- 23855987
TI  - Resolving the chemical nature of nanodesigned silica surface obtained via a
      bottom-up approach.
AB  - The covalent grafting on silica surfaces of a functional dendritic organosilane
      coupling agent inserted, in a long alkyl chain monolayer, is described. In this
      paper, we show that depending on experimental parameters, particularly the
      solvent, it is possible to obtain a nanodesigned surface via a bottom-up
      approach. Thus, we succeed in the formation of both homogeneous dense monolayer
      and a heterogeneous dense monolayer, the latter being characterized by a
      nanosized volcano-type pattern (4-6 nm of height, 100 nm of width, and around 3
      volcanos/MUm(2)) randomly distributed over the surface. The dendritic attribute
      of the grafted silylated coupling agent affords enough anchoring sites to
      immobilize covalently functional gold nanoparticles (GNPs), coated with amino PEG
      polymer to resolve the chemical nature of the surfaces and especially the volcano
      type nanopattern structures of the heterogeneous monolayer. Thus, the versatile
      surface chemistry developed herein is particularly challenging as the nanodesign
      is straightforward achieved in a bottom-up approach without any specific
      lithography device. 

PMID- 23855986
TI  - Accurate identification of fastidious Gram-negative rods: integration of both
      conventional phenotypic methods and 16S rRNA gene analysis.
AB  - BACKGROUND: Accurate identification of fastidious Gram-negative rods (GNR) by
      conventional phenotypic characteristics is a challenge for diagnostic
      microbiology. The aim of this study was to evaluate the use of molecular methods,
      e.g., 16S rRNA gene sequence analysis for identification of fastidious GNR in the
      clinical microbiology laboratory. RESULTS: A total of 158 clinical isolates
      covering 20 genera and 50 species isolated from 1993 to 2010 were analyzed by
      comparing biochemical and 16S rRNA gene sequence analysis based identification.
      16S rRNA gene homology analysis identified 148/158 (94%) of the isolates to
      species level, 9/158 (5%) to genus and 1/158 (1%) to family level. Compared to
      16S rRNA gene sequencing as reference method, phenotypic identification correctly
      identified 64/158 (40%) isolates to species level, mainly Aggregatibacter
      aphrophilus, Cardiobacterium hominis, Eikenella corrodens, Pasteurella multocida,
      and 21/158 (13%) isolates correctly to genus level, notably Capnocytophaga sp.;
      73/158 (47%) of the isolates were not identified or misidentified. CONCLUSIONS:
      We herein propose an efficient strategy for accurate identification of fastidious
      GNR in the clinical microbiology laboratory by integrating both conventional
      phenotypic methods and 16S rRNA gene sequence analysis. We conclude that 16S rRNA
      gene sequencing is an effective means for identification of fastidious GNR, which
      are not readily identified by conventional phenotypic methods.

PMID- 23855988
TI  - Influenza and respiratory syncytial virus are the major respiratory viruses
      detected from prospective testing of pediatric and adult coronial autopsies.
AB  - BACKGROUND: To ascertain the full mortality of influenza and other respiratory
      viruses, the testing of community autopsy specimens is essential. METHODS:
      Respiratory virus PCR and culture were performed on 2418 fresh unfrozen
      respiratory samples collected from 1611 coronial cases where the death was either
      unknown or infection was suspected, from July 2007 to June 2011, to detect the
      common respiratory viruses in children and adults, using standardized
      microbiological testing. RESULTS: The respiratory virus positive rate was 8.3%
      (134 cases) with a peak of 28% (42 of 151 cases) in children under 10 years of
      age. Influenza virus was the commonest respiratory virus (50 cases, 3%), followed
      by respiratory syncytial virus (RSV) (30 cases, 2%). All tested respiratory
      viruses were found in children, most commonly adenovirus, enterovirus and RSV,
      and influenza A and RSV predominated in those over 60 years, but coinfection was
      uncommon. Almost all influenza cases occurred when influenza was widely
      circulating in the community but few were diagnosed pre-mortem. Influenza and RSV
      detection was associated with bronchitis or bronchiolitis in 7 (9%) of the 80
      cases and caused pneumonia in 14 (0.8%) deaths overall. CONCLUSIONS: Our
      prospective review of respiratory viruses using standardized testing found a
      single lower respiratory tract autopsy specimen for respiratory virus PCR would
      detect most community infections at the time of death.

PMID- 23855989
TI  - Psychological processes and repeat suicidal behavior: a four-year prospective
      study.
AB  - OBJECTIVE: Although suicidal behavior is a major public health concern,
      understanding of individually sensitive suicide risk mechanisms is limited. In
      this study, the authors investigated, for the first time, the utility of defeat
      and entrapment in predicting repeat suicidal behavior in a sample of suicide
      attempters. METHOD: Seventy patients hospitalized after a suicide attempt
      completed a range of clinical and psychological measures (depression,
      hopelessness, suicidal ideation, defeat, and entrapment) while in hospital. Four
      years later, a nationally linked database was used to determine who had been
      hospitalized again after a suicide attempt. RESULTS: Over 4 years, 24.6% of
      linked participants were readmitted to hospital after a suicidal attempt. In
      univariate logistic regression analyses, defeat and entrapment as well as
      depression, hopelessness, past suicide attempts, and suicidal ideation all
      predicted suicidal behavior over this interval. However, in the multivariate
      analysis, entrapment and past frequency of suicide attempts were the only
      significant predictors of suicidal behavior. CONCLUSIONS: This longitudinal study
      supports the utility of a new theoretical model in the prediction of suicidal
      behavior. Individually sensitive suicide risk processes like entrapment could
      usefully be targeted in treatment interventions to reduce the risk of repeat
      suicidal behavior in those who have been previously hospitalized after a suicide
      attempt.

PMID- 23855990
TI  - Spatial and temporal diversity and abundance of ammonia oxidizers in semi-arid
      and arid soils: indications for a differential seasonal effect on archaeal and
      bacterial ammonia oxidizers.
AB  - Besides water, nitrogen is the limiting factor for biomass production in arid
      ecosystems. Global climatic changes are exacerbating aridity levels, and the
      response of nitrogen-transforming microorganisms to these changes is not clear
      yet. Using semi-arid and arid ecosystems as surrogates for conditions of
      increased aridity, we investigated the activity, abundance, and diversity of
      ammonia-oxidizing bacteria (AOB) and archaea (AOA) in arid and semi-arid soils.
      Ammonia oxidation potentials were higher during the winter in both sites than in
      the summer, and higher nitrate concentrations were measured in the arid soil than
      in the semi-arid soil. Denaturing gradient gel electrophoresis (DGGE) patterns of
      AOB 16S rRNA gene fragments were similar for the arid and semi-arid soils with no
      seasonal variations. In contrast, the DGGE patterns of the AOA amoA gene
      fragments differed between the sites and a soil transfer experiment suggested
      that these differences are possibly associated with soil type. AOB numbers were
      higher during the winter than in the summer, while AOA numbers were higher during
      the summer. The results indicate the resistance of AOB and AOA community
      structure to arid conditions, albeit with seasonal variations in their abundance.
      Together, the results suggest the resilience of nitrification activity to
      increased aridity level. 

PMID- 23855991
TI  - Proteomic identification of potential target proteins regulated by the SCF(F)
      (bp1) -mediated proteolysis pathway in Fusarium oxysporum.
AB  - F-box proteins function in the recruitment of proteins for SCF ubiquitination and
      proteasome degradation. Here, we studied the role of Fbp1, a nonessential F-box
      protein of the tomato pathogen Fusarium oxysporum f. sp. lycopersici. The
      Deltafbp1 mutant showed a significant delay in the production of wilt symptoms on
      tomato plants and was impaired in invasive growth on cellophane membranes and on
      living plant tissue. To search for target proteins recruited by Fbp1, a
      combination of sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS
      PAGE) and matrix-assisted laser desorption/ionization time-of-flight/time-of
      flight (MALDI-TOF/TOF) was used to compare proteins in mycelia of the wild-type
      and Deltafbp1 mutant. The proteomic approach identified 41 proteins differing
      significantly in abundance between the two strains, 17 of which were more
      abundant in the Deltafbp1 mutant, suggesting a possible regulation by proteasome
      degradation. Interestingly, several of the identified proteins were related to
      vesicle trafficking. Microscopic analysis revealed an impairment of the Deltafbp1
      strain in directional growth and in the structure of the Spitzenkorper,
      suggesting a role of Fbp1 in hyphal orientation. Our results indicate that Fbp1
      regulates protein turnover and pathogenicity in F. oxysporum. 

PMID- 23855993
TI  - [Antithrombotic therapy and pregnancy].
AB  - The incidence of venous thromboembolism (VTE) during pregnancy is about one event
      per 1000 pregnancies and placenta-mediated pregnancy complications (PC) occurred
      in 15%. Knowing the biological combined with clinical risk factors would help to
      prevent problems during the pregnancy. Several antithrombotic therapies exist,
      including very recent ones but LMWH and aspirin are still molecules of choice.
      The women should be assessed for VTE and PC risk in order to improve the outcome.

PMID- 23855992
TI  - Evolutionary age of repetitive element subfamilies and sensitivity of DNA
      methylation to airborne pollutants.
AB  - BACKGROUND: Repetitive elements take up >40% of the human genome and can change
      distribution through transposition, thus generating subfamilies. Repetitive
      element DNA methylation has associated with several diseases and environmental
      exposures, including exposure to airborne pollutants. No systematic analysis has
      yet been conducted to examine the effects of exposures across different
      repetitive element subfamilies. The purpose of the study is to evaluate
      sensitivity of DNA methylation in differentially-evolved LINE, Alu, and HERV
      subfamilies to different types of airborne pollutants. METHODS: We sampled a
      total of 120 male participants from three studies (20 high-, 20 low-exposure in
      each study) of steel workers exposed to metal-rich particulate matter (measured
      as PM10) (Study 1); gas-station attendants exposed to air benzene (Study 2); and
      truck drivers exposed to traffic-derived elemental carbon (Study 3). We measured
      methylation by bisulfite-PCR-pyrosequencing in 10 differentially-evolved
      repetitive element subfamilies. RESULTS: High-exposure groups exhibited subfamily
      specific methylation differences compared to low-exposure groups: L1PA2 showed
      lower DNA methylation in steel workers (P=0.04) and gas station attendants
      (P=0.03); L1Ta showed lower DNA methylation in steel workers (P=0.02); AluYb8
      showed higher DNA methylation in truck drivers (P=0.05). Within each study, dose
      response analyses showed subfamily-specific correlations of methylation with
      exposure levels. Interaction models showed that the effects of the exposures on
      DNA methylation were dependent on the subfamily evolutionary age, with stronger
      effects on older LINEs from PM10 (p-interaction=0.003) and benzene (p
      interaction=0.04), and on younger Alus from PM10 (p-interaction=0.02).
      CONCLUSIONS: The evolutionary age of repetitive element subfamilies determines
      differential susceptibility of DNA methylation to airborne pollutants.

PMID- 23855994
TI  - The development of a clinical screening instrument for tumour predisposition
      syndromes in childhood cancer patients.
AB  - BACKGROUND: Identification of tumour predisposition syndromes in patients who
      have cancer in childhood is paramount for optimal care. A screening instrument
      that can help to identify such patients will facilitate physicians caring for
      children with cancer. The complete screening instrument should consist of a
      standardised series of pictures and a screening form for manifestations not
      visible in the pictures. Here we describe the development of such a screening
      form based on an international two-stage Delphi process and an initial validation
      of the complete instrument. PATIENTS AND METHODS: We identified manifestations
      that may contribute to the diagnosis of a tumour predisposition syndrome through
      the Winter-Baraitser Dysmorphology Database and the textbook "Gorlin's Syndromes
      of the Head and Neck". In a two-round Delphi process, eight international content
      experts scored the contribution of each of these manifestations. We performed a
      clinical validation of the instrument in a selected cohort of 10 paediatric
      cancer patients from another centre. RESULTS: In total, 49 manifestations were
      found to contribute to the diagnosis of a tumour predisposition syndrome and were
      included in the screening form. The pilot validation study showed that patients
      suspected of having a tumour predisposition syndrome were recognised. Excellent
      correlation for indications of patient's referral between the screening
      instrument and the reference standard (personal evaluation by an experienced
      clinical geneticist) was found. CONCLUSIONS: The Delphi process performed by
      international specialists with a function as opinion leaders in their field of
      expertise, has led to a screening instrument for childhood cancer patients.
      Patients who may have a tumour predisposition syndrome and thus have an
      indication to be referred for further genetic analysis, can be identified using
      the screening instrument.

PMID- 23855995
TI  - Simplified programming and control of automated radiosynthesizers through unit
      operations.
AB  - BACKGROUND: Many automated radiosynthesizers for producing positron emission
      tomography (PET) probes provide a means for the operator to create custom
      synthesis programs. The programming interfaces are typically designed with the
      engineer rather than the radiochemist in mind, requiring lengthy programs to be
      created from sequences of low-level, non-intuitive hardware operations. In some
      cases, the user is even responsible for adding steps to update the graphical
      representation of the system. In light of these unnecessarily complex approaches,
      we have created software to perform radiochemistry on the ELIXYS radiosynthesizer
      with the goal of being intuitive and easy to use. METHODS: Radiochemists were
      consulted, and a wide range of radiosyntheses were analyzed to determine a
      comprehensive set of basic chemistry unit operations. Based around these
      operations, we created a software control system with a client-server
      architecture. In an attempt to maximize flexibility, the client software was
      designed to run on a variety of portable multi-touch devices. The software was
      used to create programs for the synthesis of several 18F-labeled probes on the
      ELIXYS radiosynthesizer, with [18F]FDG detailed here. To gauge the user
      friendliness of the software, program lengths were compared to those from other
      systems. A small sample group with no prior radiosynthesizer experience was
      tasked with creating and running a simple protocol. RESULTS: The software was
      successfully used to synthesize several 18F-labeled PET probes, including
      [18F]FDG, with synthesis times and yields comparable to literature reports. The
      resulting programs were significantly shorter and easier to debug than programs
      from other systems. The sample group of naive users created and ran a simple
      protocol within a couple of hours, revealing a very short learning curve. The
      client-server architecture provided reliability, enabling continuity of the
      synthesis run even if the computer running the client software failed. The
      architecture enabled a single user to control the hardware while others observed
      the run in progress or created programs for other probes. CONCLUSIONS: We
      developed a novel unit operation-based software interface to control automated
      radiosynthesizers that reduced the program length and complexity and also
      exhibited a short learning curve. The client-server architecture provided
      robustness and flexibility.

PMID- 23855996
TI  - An APETALA3 homolog controls both petal identity and floral meristem patterning
      in Nigella damascena L. (Ranunculaceae).
AB  - Flower architecture mutants provide a unique opportunity to address the genetic
      origin of flower diversity. Here we study a naturally occurring floral dimorphism
      in Nigella damascena (Ranunculaceae), involving replacement of the petals by
      numerous sepal-like and chimeric sepal/stamen organs. We performed a comparative
      study of floral morphology and floral development, and characterized the
      expression of APETALA3 and PISTILLATA homologs in both morphs. Segregation
      analyses and gene silencing were used to determine the involvement of an APETALA3
      paralog (NdAP3-3) in the floral dimorphism. We demonstrate that the complex
      floral dimorphism is controlled by a single locus, which perfectly co-segregates
      with the NdAP3-3 gene. This gene is not expressed in the apetalous morph and
      exhibits a particular expression dynamic during early floral development in the
      petalous morph. NdAP3-3 silencing in petalous plants perfectly phenocopies the
      apetalous morph. Our results show that NdAP3-3 is fully responsible for the
      complex N. damascena floral dimorphism, suggesting that it plays a role not only
      in petal identity but also in meristem patterning, possibly through regulation of
      perianth organ number and the perianth/stamen boundary.

PMID- 23855997
TI  - Risk of lingual nerve damage: lingual split vs ostectomy with burs.

PMID- 23855998
TI  - Physiological adaptations of Saccharomyces cerevisiae evolved for improved
      butanol tolerance.
AB  - BACKGROUND: Butanol is a chemical with potential uses as biofuel and solvent,
      which can be produced by microbial fermentation. However, the end product
      toxicity is one of the main obstacles for developing the production process
      irrespective of the choice of production organism. The long-term goal of the
      present project is to produce 2-butanol in Saccharomyces cerevisiae. Therefore,
      unraveling the toxicity mechanisms of solvents such as butanol and understanding
      the mechanisms by which tolerant strains of S. cerevisiae adapt to them would be
      an important contribution to the development of a bio-based butanol production
      process. RESULTS: A butanol tolerant S. cerevisiae was achieved through a series
      of sequential batch cultures with gradual increase of 2-butanol concentration.
      The final mutant (JBA-mut) tolerates all different alcohols tested at higher
      concentrations compared to the wild type (JBA-wt). Proteomics analysis of the two
      strains grown under mild butanol-stress revealed 46 proteins changing their
      expression by more than 1.5-fold in JBA-mut, 34 of which were upregulated.
      Strikingly, 21 out of the 34 upregulated proteins were predicted constituents of
      mitochondria. Among the non-mitochondrial up-regulated proteins, the minor
      isoform of Glycerol-3-phosphatase (Gpp2) was the most notable, since it was the
      only tested protein whose overexpression was found to confer butanol tolerance.
      CONCLUSION: The study demonstrates several differences between the butanol
      tolerant mutant and the wild type. Upregulation of proteins involved in the
      mitochondrial ATP synthesizing machinery constituents and glycerol biosynthesis
      seem to be beneficial for a successful adaptation of yeast cells to butanol
      stress.

PMID- 23856000
TI  - Determining the colloidal behavior of ionically cross-linked polyelectrolytes
      with isothermal titration calorimetry.
AB  - Mixtures of polyelectrolytes and multivalent counterions can self-assemble into
      colloidal complexes. These complexes attract widespread interest in applications
      such as medicine, household product formulations, and separation processes. To
      facilitate the development of these colloidal dispersions, we examined isothermal
      titration calorimetry (ITC) as an automated screening tool for identifying the
      polymer and multivalent counterion compositions that (1) form ionically cross
      linked colloidal complexes and (2) lead to their rapid coagulation (and
      macroscopic phase separation). By studying various polyelectrolyte/multivalent
      counterion mixtures, we have identified and generalized the features in the ITC
      data that indicate colloidal complex formation and coagulation. The limitations
      of this calorimetric screening method were also elucidated. These analyses
      suggest that ITC can be effective for screening the short-term colloidal behavior
      of polyelectrolyte/multivalent counterion mixtures but are unreliable in
      revealing their long-term (equilibrium) properties. 

PMID- 23856001
TI  - Chemically reduced graphene oxide for ammonia detection at room temperature.
AB  - Chemically reduced graphene oxide (RGO) has recently attracted growing interest
      in the area of chemical sensors because of its high electrical conductivity and
      chemically active defect sites. This paper reports the synthesis of chemically
      reduced GO using NaBH4 and its performance for ammonia detection at room
      temperature. The sensing layer was synthesized on a ceramic substrate containing
      platinum electrodes. The effect of the reduction time of graphene oxide (GO) was
      explored to optimize the response, recovery, and response time. The RGO film was
      characterized electrically and also with atomic force microscopy and X-ray
      photoelectron spectroscopy. The sensor response was found to lie between 5.5% at
      200 ppm (parts per million) and 23% at 2800 ppm of ammonia, and also resistance
      recovered quickly without any application of heat (for lower concentrations of
      ammonia). The sensor was exposed to different vapors and found to be selective
      toward ammonia. We believe such chemically reduced GO could potentially be used
      to manufacture a new generation of low-power portable ammonia sensors. 

PMID- 23855999
TI  - Interoception and drug addiction.
AB  - The role of interoception and its neural basis with relevance to drug addiction
      is reviewed. Interoception consists of the receiving, processing, and integrating
      body-relevant signals with external stimuli to affect ongoing motivated behavior.
      The insular cortex is the central nervous system hub to process and integrate
      these signals. Interoception is an important component of several addiction
      relevant constructs including arousal, attention, stress, reward, and
      conditioning. Imaging studies with drug-addicted individuals show that the
      insular cortex is hypo-active during cognitive control processes but hyperactive
      during cue reactivity and drug-specific, reward-related processes. It is proposed
      that interoception contributes to drug addiction by incorporating an "embodied"
      experience of drug uses together with the individual's predicted versus actual
      internal state to modulate approach or avoidance behavior, i.e. whether to take
      or not to take drugs. This opens the possibility of two types of interventions.
      First, one may be able to modulate the embodied experience by enhancing insula
      reactivity where necessary, e.g. when engaging in drug seeking behavior, or
      attenuating insula when exposed to drug-relevant cues. Second, one may be able to
      reduce the urge to act by increasing the frontal control network, i.e. inhibiting
      the urge to use by employing cognitive training. This article is part of a
      Special Issue entitled 'NIDA 40th Anniversary Issue'.

PMID- 23856003
TI  - A tribute to Onno van Assendelft, MD, PhD.

PMID- 23856002
TI  - Elongator subunit 3 positively regulates plant immunity through its histone
      acetyltransferase and radical S-adenosylmethionine domains.
AB  - BACKGROUND: Pathogen infection triggers a large-scale transcriptional
      reprogramming in plants, and the speed of this reprogramming affects the outcome
      of the infection. Our understanding of this process has significantly benefited
      from mutants that display either delayed or accelerated defense gene induction.
      In our previous work we demonstrated that the Arabidopsis Elongator complex
      subunit 2 (AtELP2) plays an important role in both basal immunity and effector
      triggered immunity (ETI), and more recently showed that AtELP2 is involved in
      dynamic changes in histone acetylation and DNA methylation at several defense
      genes. However, the function of other Elongator subunits in plant immunity has
      not been characterized. RESULTS: In the same genetic screen used to identify
      Atelp2, we found another Elongator mutant, Atelp3-10, which mimics Atelp2 in that
      it exhibits a delay in defense gene induction following salicylic acid treatment
      or pathogen infection. Similarly to AtELP2, AtELP3 is required for basal immunity
      and ETI, but not for systemic acquired resistance (SAR). Furthermore, we
      demonstrate that both the histone acetyltransferase and radical S
      adenosylmethionine domains of AtELP3 are essential for its function in plant
      immunity. CONCLUSION: Our results indicate that the entire Elongator complex is
      involved in basal immunity and ETI, but not in SAR, and support that Elongator
      may play a role in facilitating the transcriptional induction of defense genes
      through alterations to their chromatin.

PMID- 23856004
TI  - Effects of lysophopatidic acid on tumor necrosis factor alpha and interferon
      gamma action in the bovine corpus luteum.
AB  - We examined the effects of LPA on TNFalpha and IFNgamma - induced decrease of P4
      synthesis and on the cytokine - induced apoptosis of the cultured luteal cells.
      In the steroidogenic luteal cells LPA reversed the inhibitory effect of TNFalpha
      and IFNgamma on P4 synthesis and also inhibited the stimulatory effects of
      TNFalpha and IFNgamma on the expression of Bax, TNFR1, Fas and FasL as well as
      caspase 3 activity. These results suggest that TNFalpha and IFNgamma cannot
      induce apoptosis in the presence of LPA, which orientates the steroidogenic
      luteal cells towards the survival state. In conclusion our results indicate that
      LPA supports P4 synthesis and action in the bovine CL.

PMID- 23856005
TI  - 11beta-Hydroxydihydrotestosterone and 11-ketodihydrotestosterone, novel C19
      steroids with androgenic activity: a putative role in castration resistant
      prostate cancer?
AB  - Adrenal C19 steroids, dehydroepiandrostenedione (DHEA(S)) and androstenedione
      (A4), play a critical role in castration resistant prostate cancer (CRPC) as they
      are metabolised to dihydrotestosterone (DHT), via testosterone (T), or via the
      alternate 5alpha-dione pathway, bypassing T. Adrenal 11OHA4 metabolism in CRPC
      is, however, unknown. We present a novel pathway for 11OHA4 metabolism in CRPC
      leading to the production of 11ketoT (11KT) and novel 5alpha-reduced C19 steroids
      - 11OH-5alpha-androstanedione, 11keto-5alpha-androstanedione, 11OHDHT and
      11ketoDHT (11KDHT). The pathway was validated in the androgen-dependent prostate
      cancer cell line, LNCaP. Androgen receptor (AR) transactivation studies showed
      that while 11KT and 11OHDHT act as a partial AR agonists, 11KDHT is a full AR
      agonist exhibiting similar activity to DHT at 1nM. Our data demonstrates that,
      while 11OHA4 has negligible androgenic activity, its metabolism to 11KT and
      11KDHT yields androgenic compounds which may be implicated, together with A4 and
      DHEA(S), in driving CRPC in the absence of testicular T.

PMID- 23856006
TI  - Extreme resistance to weak-acid preservatives in the spoilage yeast
      Zygosaccharomyces bailii.
AB  - Weak-acid preservatives, such as sorbic acid and acetic acid, are used in many
      low pH foods to prevent spoilage by fungi. The spoilage yeast Zygosaccharomyces
      bailii is notorious for its extreme resistance to preservatives and ability to
      grow in excess of legally-permitted concentrations of preservatives. Extreme
      resistance was confirmed in 38 strains of Z. bailii to several weak-acid
      preservatives. Using the brewing yeast Saccharomyces cerevisiae as a control,
      tests showed that Z. bailii was ~3-fold more resistant to a variety of weak-acids
      but was not more resistant to alcohols, aldehydes, esters, ethers, ketones, or
      hydrophilic chelating acids. The weak acids were chemically very diverse in
      structure, making it improbable that the universal resistance was caused by
      degradation or metabolism. Examination of Z. bailii cell populations showed that
      extreme resistance to sorbic acid, benzoic acid and acetic acid was limited to a
      few cells within the population, numbers decreasing with concentration of weak
      acid to <1 in 1000. Re-inoculation of resistant sub-populations into weak-acid
      containing media showed that all cells now possessed extreme resistance.
      Resistant sub-populations grown in any weak-acid preservative also showed ~100%
      cross-resistance to other weak-acid preservatives. Tests using (14)C-acetic acid
      showed that weak-acid accumulation was much lower in the resistant sub
      populations. Acid accumulation is caused by acid dissociation in the higher pH of
      the cytoplasm. Tests on intracellular pH (pHi) in the resistant sub-population
      showed that the pH was much lower, ~ pH5.6, than in the sensitive bulk
      population. The hypothesis is proposed that extreme resistance to weak-acid
      preservatives in Z. bailii is due to population heterogeneity, with a small
      proportion of cells having a lower intracellular pH. This reduces the level of
      accumulation of any weak acid in the cytoplasm, thus conferring resistance to all
      weak acids, but not to other inhibitors. 

PMID- 23856007
TI  - Regional differences in species composition and toxigenic potential among
      Fusarium head blight isolates from Uruguay indicate a risk of nivalenol
      contamination in new wheat production areas.
AB  - Members of the Fusarium graminearum species complex (FGSC) are the primary cause
      of Fusarium head blight (FHB) of wheat, and frequently contaminate grain with
      trichothecene mycotoxins that pose a serious threat to food safety and animal
      health. The species identity and trichothecene toxin potential of 151 FGSC
      isolates collected from wheat in Uruguay were determined via multilocus
      genotyping. Although F. graminearum with the 15ADON trichothecene type accounted
      for 86% of the isolates examined, five different FGSC species and all three
      trichothecene types were identified in this collection. This is the first report
      of Fusarium asiaticum, Fusarium brasilicum, Fusarium cortaderiae, and Fusarium
      austroamericanum from Uruguay. In addition, we observed significant (P<0.001)
      regional differences in the composition of FGSC species and trichothecene types
      within Uruguay. Isolates of F. graminearum with the 15ADON type were the most
      prevalent in western provinces (95%), while F. asiaticum (43%) and the NIV type
      (61%) predominated in the new wheat production zone in Cerro Largo along
      Uruguay's eastern border with Brazil. F. graminearum isolates (15ADON type) were
      significantly (P<0.005) more aggressive on wheat than were isolates from the
      other species examined (NIV or 3ADON types). However, F. graminearum isolates
      (15ADON type) were significantly (P<0.05) more sensitive to tebuconazole than
      isolates from other species (NIV type). These results document substantial
      heterogeneity among the pathogens responsible for FHB in Uruguay. In addition,
      the regional predominance of the NIV trichothecene type is of significant concern
      to food safety and indicates that additional monitoring of nivalenol levels in
      grain may be required. 

PMID- 23856008
TI  - Sagittal abdominal diameter shows better correlation with cardiovascular risk
      factors than waist circumference and BMI.
AB  - BACKGROUND: Obesity (abdominal adiposity) is a risk factor for cardiovascular
      diseases and the most used methods to measure the adiposity are body mass index
      (BMI), waist circumference (WC), and sagittal abdominal diameter (SAD).
      OBJECTIVE: To correlate BMI, WC, and SAD with biochemical parameters and blood
      pressure in adults. METHODS: A non-experimental exploratory/descriptive and cross
      sectional study was developed and it was assessed 133 subjects (59 men and 74
      women) aging between 18 and 87 years. It was registered the patients' weight
      (kg), height (m), BMI (kg/m(2)), WC (cm) and SAD (cm), and these parameters were
      correlated with glycemia, triglycerides, total cholesterol, HDL-c, LDL-c and
      blood pressure. RESULTS: After adjustment for gender and age, it was observed a
      positive correlation between SAD and systolic arterial blood pressure (r = 0.20),
      glycemia (r = 0.20), triglycerides (r = 0.32), LDL (r = 0.26), total cholesterol
      (TC) (r = 0.33), and a negative correlation with HDL-c (r = -0.21) (p < 0.05). It
      was observed a positive correlation between WC and systolic arterial blood
      pressure (r = 0.14), triglycerides (r = 0.31), total cholesterol (r = 0.21), and
      a negative correlation with HDL-c (r = -0.24) (p < 0.05). BMI showed a positive
      correlation with systolic arterial blood pressure (r = 0.22), total cholesterol
      (r = 0.20), and triglycerides (r = 0.23) (p < 0.05). CONCLUSION: SAD correlated
      with almost all the cardiovascular risk factors analyzed and it might be
      considered the best predictor of abdominal fat and cardiovascular risk.

PMID- 23856009
TI  - Maternal exposure to combustion generated PM inhibits pulmonary Th1 maturation
      and concomitantly enhances postnatal asthma development in offspring.
AB  - BACKGROUND: Epidemiological studies suggest that maternal exposure to
      environmental hazards, such as particulate matter, is associated with increased
      incidence of asthma in childhood. We hypothesized that maternal exposure to
      combustion derived ultrafine particles containing persistent free radicals
      (MCP230) disrupts the development of the infant immune system and results in
      aberrant immune responses to allergens and enhances asthma severity. METHODS:
      Pregnant C57/BL6 mice received MCP230 or saline by oropharyngeal aspiration on
      gestational days 10 and 17. Three days after the second administration, blood was
      collected from MCP230 or saline treated dams and 8-isoprostanes in the serum were
      measured to assess maternal oxidative stress. Pulmonary T cell populations were
      assayed in the infant mice at six days, three and six weeks of postnatal age.
      When the infant mice matured to adults (i.e. six weeks of age), an asthma model
      was established with ovalbumin (OVA). Airway inflammation, mucus production and
      airway hyperresponsiveness were then examined. RESULTS: Maternal exposure to
      MCP230 induced systemic oxidative stress. The development of pulmonary T helper
      (Th1/Th2/Th17) and T regulatory (Treg) cells were inhibited in the infant
      offspring from MCP230-exposed dams. As the offspring matured, the development of
      Th2 and Treg cells recovered and eventually became equivalent to that of
      offspring from non-exposed dams. However, Th1 and Th17 cells remained attenuated
      through 6 weeks of age. Following OVA sensitization and challenge, mice from
      MCP230-exposed dams exhibited greater airway hyperresponsiveness, eosinophilia
      and pulmonary Th2 responses compared to offspring from non-exposed dams.
      CONCLUSIONS: Our data suggest that maternal exposure to MCP230 enhances postnatal
      asthma development in mice, which might be related to the inhibition of pulmonary
      Th1 maturation and systemic oxidative stress in the dams.

PMID- 23856010
TI  - The PEG-switch assay: a fast semi-quantitative method to determine protein
      reversible cysteine oxidation.
AB  - INTRODUCTION: Reversible protein cysteine oxidation is recognised as a pivotal
      post-transitional modification that transduces physiological as well as
      pathological signalling. Pharmacological interventions that target specific
      sources of oxidant formation are currently being trialled to ascertain their
      potential ability to prevent disease progression. To determine the selectivity of
      such pharmacological treatments and to indentify new drug targets, a suitable
      method is required to detect target cysteine oxidation. METHOD: Using a
      polyethylene glycol (PEG)-based alkylating agent the reversible oxidation of
      target proteins can be determined using a novel switch method. After reduction
      and specific labelling of reversibly oxidised thiols with a 'heavy' PEG-tag,
      samples are resolved on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) gels, Western blotted and immunostained for protein(s) of interest. A
      mobility shift in a target protein following PEG-alkylation correlates with the
      reversible oxidative modification. RESULTS: The oxidation of cAMP- and cGMP
      dependent protein kinases was detected using the PEG-switch assay in Langendorff
      perfused hearts after hydrogen peroxide was administered. DISCUSSION: The PEG
      switch assay is a fast effective semi-quantitative method for measuring target
      reversible cysteine oxidation in complex protein mixtures derived from tissue or
      cultured cells.

PMID- 23856012
TI  - Unraveling the structure of sugarcane bagasse after soaking in concentrated
      aqueous ammonia (SCAA) and ethanol production by Scheffersomyces (Pichia)
      stipitis.
AB  - BACKGROUND: Fuel ethanol production from sustainable and largely abundant agro
      residues such as sugarcane bagasse (SB) provides long term, geopolitical and
      strategic benefits. Pretreatment of SB is an inevitable process for improved
      saccharification of cell wall carbohydrates. Recently, ammonium hydroxide-based
      pretreatment technologies have gained significance as an effective and economical
      pretreatment strategy. We hypothesized that soaking in concentrated aqueous
      ammonia-mediated thermochemical pretreatment (SCAA) would overcome the native
      recalcitrance of SB by enhancing cellulase accessibility of the embedded
      holocellulosic microfibrils. RESULTS: In this study, we designed an experiment
      considering response surface methodology (Taguchi method, L8 orthogonal array) to
      optimize sugar recovery from ammonia pretreated sugarcane bagasse (SB) by using
      the method of soaking in concentrated aqueous ammonia (SCAA-SB). Three
      independent variables: ammonia concentration, temperature and time, were selected
      at two levels with center point. The ammonia pretreated bagasse (SCAA-SB) was
      enzymatically hydrolysed by commercial enzymes (Celluclast 1.5 L and Novozym 188)
      using 15 FPU/g dry biomass and 17.5 Units of beta-glucosidase/g dry biomass at 50
      degrees C, 150 rpm for 96 h. A maximum of 28.43 g/l reducing sugars corresponding
      to 0.57 g sugars/g pretreated bagasse was obtained from the SCAA-SB derived using
      a 20% v/v ammonia solution, at 70 degrees C for 24 h after enzymatic hydrolysis.
      Among the tested parameters, pretreatment time showed the maximum influence (p
      value, 0.053282) while ammonia concentration showed the least influence (p value,
      0.612552) on sugar recovery. The changes in the ultra-structure and crystallinity
      of native SCAA-SB and enzymatically hydrolysed SB were observed by scanning
      electron microscopy (SEM), x-ray diffraction (XRD) and solid-state (13)C nuclear
      magnetic resonance (NMR) spectroscopy. The enzymatic hydrolysates and solid SCAA
      SB were subjected to ethanol fermentation under separate hydrolysis and
      fermentation (SHF) and simultaneous saccharification and fermentation (SSF) by
      Scheffersomyces (Pichia) stipitis NRRL Y-7124 respectively. Higher ethanol
      production (10.31 g/l and yield, 0.387 g/g) was obtained through SSF than SHF
      (3.83 g/l and yield, 0.289 g/g). CONCLUSIONS: SCAA treatment showed marked lignin
      removal from SB thus improving the accessibility of cellulases towards
      holocellulose substrate as evidenced by efficient sugar release. The
      ultrastructure of SB after SCAA and enzymatic hydrolysis of holocellulose
      provided insights of the degradation process at the molecular level.

PMID- 23856011
TI  - A G protein-coupled receptor (GPCR) in red: live cell imaging of the kappa opioid
      receptor-tdTomato fusion protein (KOPR-tdT) in neuronal cells.
AB  - INTRODUCTION: In contrast to green fluorescent protein and variants (GFPs), red
      fluorescent proteins (RFPs) have rarely been employed for the generation of GPCR
      fusion proteins, likely because of formation of aggregates and cell toxicity of
      some RFPs. Among all the RFPs, tdTomato (tdT), one of the non-aggregating RFP,
      has the highest brightness score (about 3 times that of eGFP) and unsurpassed
      photostability. METHODS: We fused tdT to the KOPR C-terminus. The KOPR-tdT cDNA
      construct was transfected into a Neuro2A mouse neuroblastoma cell line (Neuro2A
      cells) and rat cortical primary neurons for characterization of pharmacological
      properties and imaging studies on KOPR trafficking. RESULTS: KOPR-tdT retained
      KOPR properties (cell surface expression, ligand binding, agonist-induced
      signaling and internalization) when expressed in Neuro2A cells and rat primary
      cortical neurons. Live cell imaging of KOPR-tdT enables visualization of the time
      course of agonist-induced internalization of KOPR in real time for 60 min,
      without photobleaching and apparent cell toxicity. U50,488H-induced KOPR
      internalization occurred as early as 4min and plateaued at about 30 min. A unique
      pattern of internalized KOPR in processes of primary neurons was induced by
      U50,488H. DISCUSSION: tdT is an alternative to, or even a better tool than, GFPs
      for fusion to GPCR for trafficking studies, because tdT has higher brightness and
      thus better resolution and less photobleaching problems due to the reduced laser
      power used. It also has advantages associated with its longer-wavelength emission
      including spectral separation from autofluorescence and GFPs, reduced cell
      toxicity that the laser may impose, and greater tissue penetration. These
      advantages of tdT over GPFs may be critical for live cell imaging studies of
      GPCRs in vitro and for studying GPCRs in vivo because of their low abundance.

PMID- 23856013
TI  - Cadmium uptake and partitioning in durum wheat during grain filling.
AB  - BACKGROUND: Concentrations of cadmium (Cd) in the grain of many durum wheats
      (Triticum turgidum subsp. durum) grown in North American prairie soils often
      exceed international trade standards. Genotypic differences in root-to-shoot
      translocation of Cd are a major determinant of intraspecific variation in the
      accumulation of Cd in grain. We tested the extent to which changes in whole-plant
      Cd accumulation and the distribution of Cd between tissues influences Cd
      accumulation in grain by measuring Cd accumulation throughout the grain filling
      period in two near-isogenic lines (NILs) of durum wheat that differ in grain Cd
      accumulation. RESULTS: Roots absorbed Cd and transported it to the shoots
      throughout the grain filling period, but the low- and high-Cd NILs did not differ
      in whole-plant Cd uptake. Although the majority of Cd accumulation was retained
      in the roots, the low- and high-Cd NILs differed substantively in root-to-shoot
      translocation of Cd. At grain maturity, accumulation of Cd in the shoots was 13%
      (low-Cd NIL) or 37% (high-Cd NIL) of whole-plant Cd accumulation. Accumulation of
      Cd in all shoot tissue, including grain, was at least 2-fold greater in the high
      Cd NIL at all harvests. There was no net remobilization of shoot Cd pools during
      grain filling. The timing of Cd accumulation in grain was positively correlated
      with grain biomass accumulation, and the rate of grain filling peaked between 14
      and 28 days post-anthesis, when both NILs accumulated 60% of total grain biomass
      and 61-66% of total grain Cd content. CONCLUSIONS: These results show that
      genotypic variation in root-to-shoot translocation of Cd controls accumulation of
      Cd in durum wheat grain. Continued uptake of Cd by roots and the absence of net
      remobilization of Cd from leaves during grain filling support a direct pathway of
      Cd transport from roots to grain via xylem-to-phloem transfer in the stem.

PMID- 23856015
TI  - 'Help for Hay Fever', a goal-focused intervention for people with intermittent
      allergic rhinitis, delivered in Scottish community pharmacies: study protocol for
      a pilot cluster randomized controlled trial.
AB  - BACKGROUND: Despite the availability of evidence-based guidelines for managing
      allergic rhinitis in primary care, management of the condition in the United
      Kingdom (UK) remains sub-optimal. Its high prevalence and negative effects on
      quality of life, school performance, productivity and co-morbid respiratory
      conditions (in particular, asthma), and high health and societal costs, make this
      a priority for developing novel models of care. Recent Australian research
      demonstrated the potential of a community pharmacy-based 'goal-focused'
      intervention to help people with intermittent allergic rhinitis to self-manage
      their condition better, reduce symptom severity and improve quality of life. In
      this pilot study we will assess the transferability of the goal-focused
      intervention to a UK context, the suitability of the intervention materials,
      procedures and outcome measures and collect data to inform a future definitive UK
      randomized controlled trial (RCT). METHODS/DESIGN: A pilot cluster RCT with
      associated preliminary economic analysis and embedded qualitative evaluation. The
      pilot trial will take place in two Scottish Health Board areas: Grampian and
      Greater Glasgow & Clyde. Twelve community pharmacies will be randomly assigned to
      intervention or usual care group. Each will recruit 12 customers seeking advice
      or treatment for intermittent allergic rhinitis. Pharmacy staff in intervention
      pharmacies will support recruited customers in developing strategies for setting
      and achieving goals that aim to avoid/minimize triggers for, and
      eliminate/minimize symptoms of allergic rhinitis. Customers recruited in non
      intervention pharmacies will receive usual care. The co-primary outcome measures,
      selected to inform a sample size calculation for a future RCT, are: community
      pharmacy and customer recruitment and completion rates; and effect size of change
      in the validated mini-Rhinoconjunctivitis Quality of Life Questionnaire between
      baseline, one-week and six-weeks post-intervention. Secondary outcome measures
      relate to changes in symptom severity, productivity, medication adherence and
      self-efficacy. Quantitative data about accrual, retention and economic measures,
      and qualitative data about participants' experiences during the trial will be
      collected to inform the future RCT. DISCUSSION: This work will lay the
      foundations for a definitive RCT of a community pharmacy-based 'goal-focused'
      self-management intervention for people with intermittent allergic rhinitis.
      Results of the pilot trial are expected to be available in April 2013. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN43606442.

PMID- 23856016
TI  - Development of chip-based photocatalyst-assisted reduction device to couple high
      performance liquid chromatography and inductively coupled plasma-mass
      spectrometry for determination of inorganic selenium species.
AB  - In this study, a poly(methyl methacrylate) chip-based photocatalyst-assisted
      reduction device (PMMA chip-based PCARD) was developed as a reactor based on its
      excellent optical properties and ease of fabrication. Its transmittance of
      ultraviolet light at 365nm (UV365) was found to be as high as 92% using a PMMA of
      2mm thickness. To optimize the vaporization efficiency, the effect of varying the
      depth of the geometry trenched on the PMMA-based chip was investigated. After
      optimization, it required only 29s of UV365 irradiation to vaporize the selenium
      (Se) species of interest. The PMMA-based chip was successfully used as an
      interfacing device for the hyphenation of high performance liquid chromatography
      (HPLC) separation and inductively coupled plasma-mass spectrometry (ICP-MS)
      detection. Additionally, under the optimized conditions for vaporization, using
      1gL(-1) titanium dioxide nanoparticles (nano-TiO2) at pH 5, we found that Se(IV)
      and Se(VI) were converted quantitatively into volatile Se products. In addition,
      the optimized vaporization efficiency of the Se species of interest for the
      online HPLC/PMMA chip-based PCARD/ICP-MS system enabled us to achieve detection
      limits for Se(IV) and Se(VI) in the nanogram-per-liter range (based on 3sigma). A
      series of validation experiments indicated that our proposed methods could be
      applied satisfactorily to the determination of inorganic Se species in
      environmental water samples. 

PMID- 23856014
TI  - Natural killer cells in human autoimmune disorders.
AB  - Natural killer (NK) cells are innate lymphocytes that play a critical role in
      early host defense against viruses. Through their cytolytic capacity and
      generation of cytokines and chemokines, NK cells modulate the activity of other
      components of the innate and adaptive immune systems and have been implicated in
      the initiation or maintenance of autoimmune responses. This review focuses on
      recent research elucidating a potential immunoregulatory role for NK cells in T
      cell and B-cell-mediated autoimmune disorders in humans, with a particular focus
      on multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous. A
      better understanding of the contributions of NK cells to the development of
      autoimmunity may lead to novel therapeutic targets in these diseases. 

PMID- 23856017
TI  - Pneumatic nebulization gas-solid extraction of triazine herbicides in vegetable.
AB  - The pneumatic nebulization gas-solid extraction (PN-GSE) high-performance liquid
      chromatography (HPLC) was developed and applied to the extraction, separation and
      determination of triazine herbicides in vegetables. The herbicides were
      ultrasonically extracted from vegetables with 70% methanol in water. Then the
      extract was introduced to PN-GSE system to further clean-up. The experimental
      parameters, including type and concentration of extraction solvent, ratio of
      solvent to sample, pH value of sample solution and PN-GSE solution, extraction
      time, temperature, type of sorbent, flow rate of carrier gas, pumping rate of
      gas, and kind and volume of elution solvent, were investigated and optimized. The
      limits of detection for seven herbicides range from 0.59 to 1.05MUg/kg. The
      recoveries of the herbicides are in the range of 86.2-110.6% and relative
      standard deviations are equal or less than 7.51%, when the present method was
      applied to the analysis of spiked samples. The present method was applied to the
      analysis of real samples and the results were satisfactory. 

PMID- 23856018
TI  - Lipid production for biofuels from hydrolyzate of waste activated sludge by
      heterotrophic Chlorella protothecoides.
AB  - Microalga Chlorella protothecoides can accumulate high proportion of lipids
      during the heterotrophic growth with glucose as the carbon source. However, its
      commercial application is restricted due to the high cost of the carbon source.
      In this study, the wasted activated sludge (WAS) was hydrolyzed after ultrasonic
      pre-treatment and the hydrolyzate obtained was used as an alternative carbon
      source for algal biomass and biodiesel production. The results indicate that C.
      protothecoides can proliferate in the WAS hydrolyzate and accumulate biolipid.
      The final lipid content of the culture fed with the hydrolyzate was 21.5+/-1.44%
      (weight percent) after 156 h cultivation in flasks and the maximum biomass
      obtained was 0.5 g L(-1). Acetic acid and isovaleric acid were favorable carbon
      sources for cell growth. The soluble microbial products (SMP) presents in the
      hydrolyzate can also be used as a carbon source for cell growth.

PMID- 23856019
TI  - Treatability study of 3,3',4',5-tetrachlorosalicylanilide (TCS) combined with
      2,4,6-trichlorophenol (TCP) to reduce excess sludge production in a sequence
      batch reactor.
AB  - The present study investigated the synergistic effects of a novel combined
      uncoupler of TCS and TCP on excess activated sludge reduction during a 60-day
      operation using a sequence batch reactor (SBR). Response surface methodology
      (RSM) was employed to obtain the optimal dosage of the combined uncoupler. The
      results of 60-day operation demonstrated the combined uncoupler had effectively
      reduced the sludge yield by approximately 52%, without serious affecting the
      substrate removal efficiency. The high sludge reduction rate revealed that it was
      feasible and effective to utilize a combined uncoupler to limit excess activated
      sludge. The three-dimensional excitation-emission matrix (EEM) fluorescence
      spectroscopy analysis of activated sludge with different metabolic uncouplers
      indicated that tryptophan, tyrosine protein-like substances and tryptophan,
      tyrosine amino-like substances were reduced by adding a combined uncoupler.
      Moreover, the variation of sludge components provided a better understanding of
      the effects of uncouplers on activated sludge reduction. 

PMID- 23856020
TI  - Transesterification of soybean oil using bovine bone waste as new catalyst.
AB  - Calcined bovine bone waste was employed to catalyze the transesterification
      reaction between soybean oil and methanol. The influence of various conditions on
      the efficiency of the transesterification was studied i.e. type of reactor,
      temperature, catalyst loading and methanol/oil ratio. The optimum yield of methyl
      ester (97%) was obtained by performing the closed-system transesterification at
      65  degrees C for 3 h with catalyst loading of 8% wt and 6:1 methanol to oil
      ratio, using bone calcined at 750  degrees C. Calcination of the commercial
      bovine bone at 650  degrees C and above results in conversion of the calcium
      carbonate component to calcium oxide, with the major component being crystalline
      hydroxyapetite. Calcium oxide is believed to be responsible for the catalytic
      activity of the material. The reusability, low cost and low catalyst loading
      required (4% wt) may make bovine bone an attractive alternative to existing
      transesterification catalyst systems.

PMID- 23856021
TI  - Classification of myocardial infarction: frequency and features of type 2
      myocardial infarction.
AB  - BACKGROUND: The classification of myocardial infarction into 5 types was
      introduced in 2007 as an important component of the universal definition. In
      contrast to the plaque rupture-related type 1 myocardial infarction, type 2
      myocardial infarction is considered to be caused by an imbalance between demand
      and supply of oxygen in the myocardium. However, no specific criteria for type 2
      myocardial infarction have been established. METHODS: We prospectively studied
      unselected hospital patients who had cardiac troponin I measured on clinical
      indication. The diagnosis and classification of myocardial infarction were
      established, and the frequency and features of type 2 myocardial infarction were
      investigated by use of novel developed criteria. RESULTS: From January 2010 to
      January 2011, a total of 7230 consecutive patients who had cardiac troponin I
      measured were evaluated, and 4499 patients qualified for inclusion. The diagnosis
      of myocardial infarction was established in 553 patients, of whom 386 (72%) had a
      type 1 myocardial infarction and 144 (26%) had a type 2 myocardial infarction.
      Patients in the group with type 2 myocardial infarction were older and more
      likely to be female, and had more comorbidities. The proportion of patients
      without significant coronary artery disease was higher in those with type 2
      myocardial infarction (45%) than in those with type 1 myocardial infarction (12%)
      (P < .001). Tachyarrhythmias, anemia, and respiratory failure were the most
      prevalent mechanisms causing type 2 myocardial infarction. CONCLUSIONS: In a
      cohort of patients with myocardial infarction who were admitted consecutively
      through 1 year, the category of type 2 myocardial infarction comprised one fourth
      when diagnosed by the use of newly developed criteria. Approximately half of
      patients with type 2 myocardial infarction had no significant coronary artery
      disease.

PMID- 23856022
TI  - Wiping versus suction to clear neonatal airways at birth.

PMID- 23856023
TI  - [News in cystic fibrosis].
AB  - The improvement over the last two decades in the treatment of cystic fibrosis led
      to an increase in life expectancy approaching 40 years at birth. Logically, the
      population of adult patients has been increasing and is currently 50% of patients
      followed in France. These therapeutic advances have justified the establishment
      in 2003 of a generalized neonatal screening for cystic fibrosis. The latest data
      of this screening show an incidence of CF of 1/5359 live births, far below the
      incidence of 1/2500 which was widely accepted twenty years ago. The performance
      of this screening is currently based on the dosage of trypsin immuno reactive,
      followed in case of exceeding the threshold of a search of the 30 most common
      mutations, can detect around 96% of 150 to 200 CF cases every year. Therefore,
      the possibility of a false negative of the screening cannot be excluded and
      evocative symptoms of cystic fibrosis, even for children born after 2003, will
      lead to prescribe a sweat test. While treatments available so far goal
      consequences of cystic fibrosis, a new therapeutic class to correct the
      functional defect of the mutated protein, called CFTR modulators, is emerging.
      Ivacaftor, leader of this new class, belonging to the category of "CFTR
      potentiator" got its access on the market in September 2012 for patients carrying
      the G551D mutation. New other molecules, named "CFTR correctors" which can have
      synergistic effect with ivacaftor and concern patients carrying the most common
      mutation--DF 508--are under development.

PMID- 23856025
TI  - Human cooperation.
AB  - Why should you help a competitor? Why should you contribute to the public good if
      free riders reap the benefits of your generosity? Cooperation in a competitive
      world is a conundrum. Natural selection opposes the evolution of cooperation
      unless specific mechanisms are at work. Five such mechanisms have been proposed:
      direct reciprocity, indirect reciprocity, spatial selection, multilevel
      selection, and kin selection. Here we discuss empirical evidence from laboratory
      experiments and field studies of human interactions for each mechanism. We also
      consider cooperation in one-shot, anonymous interactions for which no mechanisms
      are apparent. We argue that this behavior reflects the overgeneralization of
      cooperative strategies learned in the context of direct and indirect reciprocity:
      we show that automatic, intuitive responses favor cooperative strategies that
      reciprocate. 

PMID- 23856024
TI  - [Lung diseases in children associated with inherited disorders of surfactant
      metabolism].
AB  - Pulmonary surfactant is a unique mixture of lipids and specific proteins that
      reduces surface tension at the air-liquid interface, preventing collapse of the
      lung at the end of expiration. Recessive loss-of-function mutations of pulmonary
      surfactant protein B (SP-B) was initially described in infants who develop
      respiratory failure at birth. More recently, mutations in other constitutive
      surfactant proteins like surfactant protein C or implied in its metabolism like
      ATP-binding cassette, sub-family A, member 3 (ABCA3) or NK2 homeobox (NKX2-1)
      were identified in newborn with respiratory distress but also in children with
      diffuse infiltrative pneumonia. Intra-alveolar accumulation of protein related to
      surfactant dysfunction leads to cough, hypoxemia and radiological abnormalities
      including ground-glass opacities and lung cysts. The clinical and radiological
      features associated with these genetic disorders, along with their treatment and
      outcome, are reviewed. 

PMID- 23856026
TI  - International spotlight: developing a gerontological social policy agenda for
      Turkey.
AB  - From 1960 to 2013, the population of Turkey increased almost threefold, with
      older adults aged 65 and older increasing almost sevenfold. In light of the
      demographic revolution in the age composition of world populations, we
      investigated the following research questions from the perspective of Turkish
      gerontologists: What are the conditions of older people based on sociological
      factors such as gender, partnership status, income, education, health, religion,
      and ethnicity? What should Turkey's gerontological agenda contain for the short
      term, mid-term, and long term, particularly in view of the rapidly changing
      nature of political, social, and economic life in the country? By 2025, adults
      (aged 40-65) will make up the largest population group in Turkey's history. It is
      time for Turkey to embrace this demographic gift and identify its own
      gerontological agenda to pave the way for social justice and social citizenship. 

PMID- 23856027
TI  - The Hidden Complexity of Long-Term Care: how context mediates knowledge
      translation and use of best practices.
AB  - PURPOSE: Context is increasingly recognized as a key factor to be considered when
      addressing healthcare practice. This study describes features of context as they
      pertain to knowledge use in long-term care (LTC). DESIGN AND METHODS: As one
      component of the research program Translating Research in Elder Care, an in-depth
      qualitative case study was conducted to examine the research question "How does
      organizational context mediate the use of knowledge in practice in long-term care
      facilities?" A representative facility was chosen from the province of
      Saskatchewan, Canada. Data included document review, direct observation of daily
      care practices, and interviews with direct care, allied provider, and
      administrative staff. RESULTS: The Hidden Complexity of Long-Term Care model
      consists of 8 categories that enmesh to create a context within which knowledge
      exchange and best practice are executed. These categories range from the most
      easily identifiable to the least observable: physical environment, resources,
      ambiguity, flux, relationships, and philosophies. Two categories (experience and
      confidence, leadership and mentoring) mediate the impact of other contextual
      factors. Inappropriate physical environments, inadequate resources, ambiguous
      situations, continual change, multiple relationships, and contradictory
      philosophies make for a complicated context that impacts care provision.
      IMPLICATIONS: A hidden complexity underlays healthcare practices in LTC and each
      care provider must negotiate this complexity when providing care. Attending to
      this complexity in which care decisions are made will lead to improvements in
      knowledge exchange mechanisms and best practice uptake in LTC settings.

PMID- 23856029
TI  - Long noncoding RNAs: new players in prostate cancer.
AB  - Prostate cancer is the most common type of cancer and frequent cause of cancer
      related mortality in men worldwide. Despite its commonness, the underlying
      molecular mechanism of prostate cancer is not completely understood. Long
      noncoding RNAs (lncRNAs) are being implicated in the complex network of an
      apparent cancer initiatome and hundreds of lncRNAs are differentially expressed
      in various types of cancer including prostate cancer. While many lncRNAs exhibit
      oncogenic function and are named "Onco-lncRNAs", only a few lncRNAs inhibit cell
      proliferation or induce apoptosis and, hence, act as tumor suppressors. In this
      review, we highlight recent findings of emerging roles for lncRNAs in prostate
      cancer and discuss rapid translational lncRNA research for clinical application
      in diagnosis, prognosis and potential treatment.

PMID- 23856028
TI  - Recombinant leukemia inhibitory factor suppresses human medullary thyroid
      carcinoma cell line xenografts in mice.
AB  - Medullary thyroid carcinoma (MTC) is a neoplasm of the endocrine system, which
      originates from parafollicular C-cells of the thyroid gland. For MTC therapy, the
      Food and Drug Administration recently approved vandetanib and cabozantinib, multi
      kinase inhibitors targeting RET and other tyrosine kinase receptors of vascular
      endothelial growth factor, epidermal growth factor, or hepatocyte growth factor.
      Nevertheless, not all patients with the progressive MTC respond to these drugs,
      requiring the development of additional therapeutic modalities that have distinct
      activity. Previously, we reported that expression of activated Ras or Raf in the
      human MTC cell lines, TT and MZ-CRC-1, can induce growth arrest and RET
      downregulation via a leukemia inhibitory factor (LIF)-mediated
      autocrine/paracrine loop. In this study, we aimed to evaluate bacterially
      produced recombinant human LIF for its efficacy to suppress human MTC xenografts
      in mice. Here, we report that, consistent with its effects in vitro, locally or
      systemically administered recombinant LIF effectively suppressed growth of TT and
      MZ-CRC-1 xenografts in mice. Further, as predicted from its effects in TT and MZ
      CRC-1 cell cultures in vitro, recombinant LIF activated the JAK/STAT pathway and
      downregulated RET and E2F1 expression in tumors in mice. These results suggest
      that LIF is a potent cytostatic agent for MTC cells, which regulates unique
      mechanisms that are not targeted by currently available therapeutic agents.

PMID- 23856030
TI  - IC-4, a new irreversible EGFR inhibitor, exhibits prominent anti-tumor and anti
      angiogenesis activities.
AB  - Accumulating evidence suggested that the irreversible tyrosine kinase inhibitors
      (TKIs) have potential to override the acquired resistance to target-based
      therapies. Herein, we reported IC-4 as a novel irreversible TKI for epidermal
      growth factor receptor (EGFR). IC-4 potentially suppressed proliferation, induced
      apoptosis and a G2/M cell cycle arrest in breast cancer cells, correlating with
      inhibition of EGF-induced EGFR activation, but independent of DNA damage. In
      addition, IC-4 exhibited anti-angiogenetic activities both in vitro and in vivo.
      It suppressed cell viability and proliferation induced by various growth factors
      in human umbilical vein endothelial cells (HUVECs). IC-4 also inhibited HUVECs
      migration and tube formation. In transgenic zebrafish embryo model, IC-4 was
      shown to suppress formation of intersegmental vessel and development of
      subintestinal vessels. Taken together, these results demonstrated that IC-4 is a
      new irreversible EGFR-TKI, exhibiting potent anti-breast cancer and anti
      angiogenetic effects. 

PMID- 23856031
TI  - Antitumor activities of the targeted multi-tyrosine kinase inhibitor lenvatinib
      (E7080) against RET gene fusion-driven tumor models.
AB  - RET gene fusions are recurrent oncogenes identified in thyroid and lung
      carcinomas. Lenvatinib is a multi-tyrosine kinase inhibitor currently under
      evaluation in several clinical trials. Here we evaluated lenvatinib in RET gene
      fusion-driven preclinical models. In cellular assays, lenvatinib inhibited auto
      phosphorylation of KIF5B-RET, CCDC6-RET, and NcoA4-RET. Lenvatinib suppressed the
      growth of CCDC6-RET human thyroid and lung cancer cell lines, and as well,
      suppressed anchorage-independent growth and tumorigenicity of RET gene fusion
      transformed NIH3T3 cells. These results demonstrate that lenvatinib can exert
      antitumor activity against RET gene fusion-driven tumor models by inhibiting
      oncogenic RET gene fusion signaling. 

PMID- 23856032
TI  - FOXM1 promotes the epithelial to mesenchymal transition by stimulating the
      transcription of Slug in human breast cancer.
AB  - The Forkhead Box M1 (FOXM1) transcription factor is involved in tumorigenesis and
      tumor progression in multiple human carcinomas. In this study, we found that
      FOXM1 promoted the epithelial to mesenchymal transition (EMT) in human breast
      cancer. We observed a strong correlation between the expression levels of FOXM1
      and the mesenchymal phenotype. Knockdown of FOXM1 inhibited the mesenchymal
      phenotype, whereas stable overexpression of FOXM1 induced EMT in breast cancer
      cells. FOXM1 was found to endogenously bind to and stimulate the promoter of Slug
      that is crucial for EMT progression. The knockdown of Slug abolished the EMT
      inducing function of FOXM1. The stable overexpression of FOXM1 promoted
      metastasis of breast cancer cells in vivo. This study confirmed that FOXM1
      promoted EMT in breast cancer cells by stimulating the transcription of EMT
      related genes such as Slug. 

PMID- 23856033
TI  - Development of noncytotoxic PLGA nanoparticles to improve the effect of a new
      inhibitor of p53-MDM2 interaction.
AB  - One possible approach to overcome solubility complications and enhance the
      biological activity of drugs is their incorporation into drug delivery systems.
      Within this scope, several nanosphere and nanocapsule formulations of a new
      inhibitor of p53-MDM2 interaction (xanthone 1) were developed and their
      physicochemical properties analyzed. Through the investigation of the effect of
      several empty nanoparticles on the growth of MCF-7 cells, it was possible to
      observe that four out of five formulations were cytotoxic and that some
      correlations between the toxic potential of these polymeric nanoparticles and
      their properties/composition could be extrapolated. One empty formulation of
      nanocapsules developed by emulsification/solvent evaporation and containing PLGA,
      PVA and Mygliol((r)) 812 was found to be noncytotoxic to this cell line. The
      corresponding compound 1-loaded nanocapsules showed an incorporation efficiency
      of 77% and revealed to be more potent than the free drug against cell growth
      inhibition, which may be related to the enhancement in its intracellular
      delivery. In an integrative study, the intracellular uptake of nanocapsules was
      confirmed using fluorescent 6-coumarin and well as compound 1 release from
      nanocapsules. Overall, it was possible to enhance the effect of the hit inhibitor
      of p53-MDM2 interaction through the development of suitable noncytotoxic
      polymeric nanoparticles. 

PMID- 23856034
TI  - [Mechanical venous microanastomosis using a double ring eversion system in
      reconstructive surgery].
AB  - INTRODUCTION: The major complications of free flap surgery are anastomotic
      obstructions. The coupler, mechanical anastomosis using a double ring eversion
      system, yields higher venous patency rates than sutured anastomoses, and requires
      less operating time. We present our initial experience with this coupler in free
      flap surgery. MATERIAL AND METHODS: We conducted this retrospective study between
      November 2011 and June 2012. We focused on complications having occurred in the
      first 10 patients having undergone free flap reconstruction (11 flaps) with end
      to-end venous anastomosis using this coupler. Five flaps were used to fill
      cervico-facial defects in carcinologic surgery: one for mandibular
      osteoradionecrosis, one for cranioplasty coverage, one for cranial base
      reconstruction, two for skin defects in lower limb (heel, leg). One was an
      antebrachial radial flap, four anterolateral thigh flaps, five fibular flaps, and
      one latissimus dorsi flap. Fifteen veins were anastomosed. The diameters of the
      couplers used were 2.5 mm (3/15), 3 mm (6/15), and 3.5 mm (6/15). RESULTS: There
      were no venous complications. One flap failed because of arterial ischemia.
      DISCUSSION: The coupler is a fast and reliable alternative to usual sutures in
      free flap reconstructions, for head and neck as well as for limbs.

PMID- 23856035
TI  - AIDS and the pancreas in the HAART era: a cross sectional study.
AB  - BACKGROUNDS: The aim of this study is identify the main morphological patterns of
      the pancreas in AIDS patients in use of Higly Active Antiretorviral Therapy
      (HAART). METHODS: We conducted a cross sectional study in the year of 2010. The
      inclusion criteria were patients older than 18 years who died of AIDS with the
      use of HAART (2006-2009) and underwent to autopsy . They were compared with a
      group of 109 patients who died of AIDS in 1995 before the HAART therapy. All the
      autopsies were made in the Death Verification Service of Sao Paulo. RESULTS: The
      HAART group presented pancreas abnormalities lighter than no HAART users. In the
      HAART group, histology shows: reduction of zymogen granules in the acinar cells
      (ZG) higher percentage of cases, "dysplasia-like" presents lower and pancreatic
      acinar atrophy, presents higher percentage of cases compared to no HAART group.
      The exocrine pancreas in treated patients was distinguished by the high level of
      atrophy, sharp reduction of zymogen granules and high level of apoptosis,
      reflecting degeneration and lower level of protein-caloric malnutrition.
      CONCLUSIONS: The islets of Langerhans in HAART group were increased in number and
      volume and with high level of nuclear dysplasia. The antiviral therapy and a
      longer survival resulted in a higher atrophy and reduction of enzymes, increasing
      the apoptosis and generated important changes in the pancreatic islets, probably
      resulting in clinical laboratory repercussion.We found no evidence of pancreatic
      histopathological lesions secondary to antiretroviral therapy.

PMID- 23856036
TI  - Beyond the learning curve of the Retzius-sparing approach for robot-assisted
      laparoscopic radical prostatectomy: oncologic and functional results of the first
      200 patients with >= 1 year of follow-up.
AB  - BACKGROUND: Robot-assisted laparoscopic radical prostatectomy (RARP) has become
      the main surgical option for localized prostate cancer. We recently developed a
      new approach for RARP, passing through the pouch of Douglas and avoiding all the
      Retzius structures involved in continence and potency preservation. OBJECTIVE: To
      report the functional and oncologic results of our first 200 patients operated on
      using this new approach. DESIGN, SETTING, AND PARTICIPANTS: This was a
      prospective, noncontrolled case series including the first 200 consecutive
      patients undergoing this kind of surgery (January the 1st, 2010 to December the
      31st, 2011). SURGICAL PROCEDURE: Retzius-sparing RARP. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: All perioperative, oncologic, and functional data were
      prospectively recorded. Potency was defined as an International Index of Erectile
      Function-5 questionnaire score >17; continence was defined as use of no pad or of
      one safety liner. Oncologic results were reported as positive surgical margins
      (PSM) and 1-yr biochemical disease-free survival (1y-bDFS). Recurrence was
      defined as a repeated prostate-specific antigen >0.2 ng/ml. Complications were
      graded according to the Clavien-Dindo system. The first 100 patients (group 1)
      were compared with the second 100 (group 2) to evaluate the learning curve
      effects. RESULTS AND LIMITATIONS: The median patient age was 65 yr. Comparing the
      two groups, transfusions were needed in 8% versus 4% of cases in groups 1 and 2,
      respectively (p=0.02). There was one Clavien-Dindo grade 3b in group 1 versus one
      grade 3a complication in group 2. In patients with pT2 disease, PSMs were
      recorded in 22.4% of those in group 1 versus 10.1% in group 2 (p=0.045). 1y-bDFS
      was 89% in group 1 versus 92% in group 2. For groups 1 and 2, respectively,
      immediate continence was reached in 92% versus 90% of patients, and the 1-yr
      continence rate was 96% versus 96%. Considering the 77 potent patients aged <65
      yr who underwent bilateral intrafascial nerve-sparing surgery, 40.4% of those in
      group 1 versus 40% of those in group 2 reached their first intercourse within 1
      mo; at 1 yr of follow-up, these figures had increased to 81% versus 71%,
      respectively (p=0.162). The main limitation of this study is its noncontrolled
      nature. CONCLUSIONS: We demonstrated Retzius-sparing RARP to be oncologically
      safe and to result in high early continence and potency rates. Long-term,
      prospective, comparative, and possibly randomized studies are needed.

PMID- 23856037
TI  - Robot-assisted and laparoscopic repair of ureteropelvic junction obstruction: a
      systematic review and meta-analysis.
AB  - CONTEXT: Over the last two decades, minimally invasive treatment options for
      ureteropelvic junction obstruction (UPJO) have been developed and popularized.
      OBJECTIVE: To critically analyze the current status of laparoscopic and robotic
      repair of UPJO. EVIDENCE ACQUISITION: A systematic literature review was
      performed in November 2012 using PubMed. Article selection proceeded according to
      the search strategy based on Preferred Reporting Items for Systematic Reviews and
      Meta-analyses criteria. EVIDENCE SYNTHESIS: Multiple series of laparoscopic
      pyeloplasty have demonstrated high success rates and low perioperative morbidity
      in pediatric and adult populations, with both the transperitoneal and
      retroperitoneal approaches. Data on pediatric robot-assisted pyeloplasty are
      increasingly becoming available. A larger number of cases have also been reported
      for adult patients, confirming that robotic pyeloplasty represents a viable
      option for either primary or secondary repair. Robot-assisted redo pyeloplasty
      has been mostly described in the pediatric population. Different technical
      variations have been implemented with the aim of tailoring the procedure to each
      specific case. The type of stenting, retrograde versus antegrade, continues to be
      debated. Internal-external stenting as well as a stentless approach have been
      used, especially in the pediatric population. Comparative studies demonstrate
      similar success and complication rates between minimally invasive and open
      pyeloplasty in both the adult and pediatric setting. A clear advantage in terms
      of hospital stay for minimally invasive over open pyeloplasty was observed only
      in the adult population. CONCLUSIONS: Laparoscopy represents an efficient and
      effective less invasive alternative to open pyeloplasty. Robotic pyeloplasty is
      likely to emerge as the new minimally invasive standard of care whenever robotic
      technology is available because its precise suturing and shorter learning curve
      represent unique attractive features. For both laparoscopy and robotics, the
      technique can be tailored to the specific case according to intraoperative
      findings and personal surgical experience.

PMID- 23856038
TI  - Early detection of prostate cancer: European Association of Urology
      recommendation.
AB  - BACKGROUND: The recommendations and the updated EAU guidelines consider early
      detection of PCa with the purpose of reducing PCa-related mortality and the
      development of advanced or metastatic disease. OBJECTIVE: This paper presents the
      recommendations of the European Association of Urology (EAU) for early detection
      of prostate cancer (PCa) in men without evidence of PCa-related symptoms.
      EVIDENCE ACQUISITION: The working panel conducted a systematic literature review
      and meta-analysis of prospective and retrospective clinical studies on baseline
      prostate-specific antigen (PSA) and early detection of PCa and on PCa screening
      published between 1990 and 2013 using Cochrane Reviews, Embase, and Medline
      search strategies. EVIDENCE SYNTHESIS: The level of evidence and grade of
      recommendation were analysed according to the principles of evidence-based
      medicine. The current strategy of the EAU recommends that (1) early detection of
      PCa reduces PCa-related mortality; (2) early detection of PCa reduces the risk of
      being diagnosed and developing advanced and metastatic PCa; (3) a baseline serum
      PSA level should be obtained at 40-45 yr of age; (4) intervals for early
      detection of PCa should be adapted to the baseline PSA serum concentration; (5)
      early detection should be offered to men with a life expectancy >= 10 yr; and (6)
      in the future, multivariable clinical risk-prediction tools need to be integrated
      into the decision-making process. CONCLUSIONS: A baseline serum PSA should be
      offered to all men 40-45 yr of age to initiate a risk-adapted follow-up approach
      with the purpose of reducing PCa mortality and the incidence of advanced and
      metastatic PCa. In the future, the development and application of multivariable
      risk-prediction tools will be necessary to prevent over diagnosis and over
      treatment.

PMID- 23856039
TI  - Mesh sling in an era of uncertainty: lessons learned and the way forward.
AB  - Following transvaginal mesh, synthetic slings to correct stress urinary
      incontinence have been put under further scrutiny. Since the recent FDA website
      update, we reviewed the latest developments and then reflected on the lessons
      learned by applying this process and the way forward. 

PMID- 23856040
TI  - Reply from authors re: Hebert Alberto Vargas, Hedvig Hricak. Magnetic resonance
      imaging-targeted prostate biopsies: now is the time to START. Eur Urol
      2013;64:553-4: START: the beginning of a multidisciplinary effort to define the
      role of MRI-targeted Biopsy in the detection of clinically significant prostate
      cancer.

PMID- 23856041
TI  - Spectroscopic studies of wood fossils from the Crato Formation, Cretaceous
      Period.
AB  - In this work we study two types of wood fossils (Gymnosperms, Araucariaceae) from
      the Crato Formation of Araripe Basin in Brazil, from the Cretaceous Period. The
      samples were characterized by Raman and infrared spectroscopies, X-ray
      diffraction and scanning electron microscopy. The results obtained by different
      techniques showed that although the rocks surrounding the fossils have
      predominantly the same constitution - calcite - however, the formation processes
      of these types of wood fossils are quite different. One of the fossils,
      denominated as light wood, is predominantly composed of gypsum, while the other
      fossil, the dark wood, is rich in amorphous carbon, possibly the kerogen type.
      Implications relative to the environment where the plants lived millions years
      ago are also given. Finally, the results highlight the constitution of one of the
      most important paleontological sites of the Cretaceous Period in the South
      America. 

PMID- 23856042
TI  - Aspartic acid functionalized water-soluble perylene diimide as "Off-On"
      fluorescent sensor for selective detection Cu(2+) and ATP.
AB  - Aspartic functionalized water-soluble perylene diimide, N,N'-di(2-succinic acid)
      perylene-3,4,9,10-tetracarboxylic diimide (PASP) has two absorbance maximums at
      527 and 498nm (epsilon~1.7*10(4)Lcm(-1)mol(-1)) and two emission peaks at 547 and
      587nm respectively. Emission intensities decrease with the increase of PASP
      concentrations in 20-100MUM ranges. Spectral titrations demonstrate that each
      PASP can coordinate to two Cu(2+) ions in the absence of HEPES buffer. Its
      stability constant is estimated to be about 1.0*10(12)L(2)mol(-2) at pH 7.20 and
      its coordinate stoichiometry increased to 7.5 in the same pH in the presence of
      HEPES buffer. The emission of PASP will be completely quenched upon formation of
      Cu(2+) complex. The lowest "turn-off" fluorescence detection limit was calculated
      to be 0.3MUM Cu(2+). PASP-Cu solution was used as a "turn-on" fluorescence
      biosensor to detect ATP. The sensitivity towards ATP is 0.3MUM in 50mM HEPES
      buffer at pH 7.20, which is one of the most sensitive fluorescence sensors. 

PMID- 23856043
TI  - Aberrant cortico-subcortical functional connectivity among women with poor motor
      control: toward uncovering the substrate of hyperkinetic perseveration.
AB  - OBJECTIVE: Hyperkinetic perseveration (HKP) refers to perseverative repetition of
      rudimentary motor output. Although HKP is known to be associated with brain
      injuries and certain neurodegenerative disorders (primarily those involving the
      frontal lobes and the basal ganglia), an increased tendency to exhibit HKP is
      also commonly associated with apparently normal aging (i.e., in the absence of
      known neuropathology). The purpose of the present study was to examine anomalies
      in brain functioning associated with HKP tendencies in a non-injured brain.
      METHOD: The present study examined functional MRI connectivity patterns
      associated with HKP in a sample of 24 "young" (ages 25-35 years) and 20 "old"
      (ages 65-75 years) healthy community dwelling women. Participants performed a
      motor learning task (the Push-Turn-Taptap task: PTT) known to elicit HKP. On a
      separate day, participants were scanned on a Siemens 3T Trio MR scanner with a 12
      channel head coil, while performing a block-design motor sequence learning task
      that was designed to be a scanner analog for the PTT task. Cortico-subcortical
      connectivity patterns involving two subcortical regions of interest (putamen and
      thalamus) and three cortical regions (sensory-motor cortex, Brodmann Area 6,
      inferior frontal gyrus) were examined. RESULTS: Older participants exhibited a
      higher rate of HKP compared to younger participants. Age-related HKP was
      associated with hemispheric asymmetry marked by a relatively stronger right
      hemisphere cortico-subcortical connectivity involving the sensory-motor cortex
      and, to a lesser extent, Brodmann Area 6. These patterns were distinct from
      connectivity patterns associated with aging alone. CONCLUSIONS: HKP is related to
      anomalies involving frontal-subcortical circuits. Future research should examine
      specific components of the basal-ganglia circuitry.

PMID- 23856045
TI  - Porphyromonas gingivalis peptidylarginine deiminase substrate specificity.
AB  - While a group of oral commensals have been implicated in the aetiology of chronic
      periodontitis; the asaccharolytic Gram negative anaerobe Porphyromonas gingivalis
      is most commonly reported to be associated with severe forms of the disease.
      Although a variety of human tissues can produce a number of peptidylarginine
      deiminase (PAD), enzymes that convert peptide bound arginine residues to
      citrulline, P. gingivalis is one of the few prokaryotes known to express PAD.
      Protein and peptide citrullination are important in the development of rheumatoid
      arthritis and in recent years a number of authors have suggested a possible link
      between periodontitis and rheumatoid arthritis (RA). Indeed, some have linked P.
      gingivalis directly to RA via the action of PAD. Accordingly, the prime purpose
      of this study was to further characterise PAD in P. gingivalis cells particular
      emphasis on substrate specificity, using arginine containing peptides and RA
      relevant proteins. METHODS: P. ginigvalis W50 was anaerobically cultured in BHI
      broth, cells harvested and resuspended in assay buffer. A colourimetric assay was
      developed to measure citrulline and employed to determine enzyme activity using
      the substrate BAEE. The assay was employed to investigate the effects of
      environmental pH and temperature on activity. Citrullination of BAEE by sonicated
      cells allowed the proportion of intracellular enzyme to be estimated. Enzyme
      specificity and substrate preference were investigated by using various arginine
      containing peptides, proteins and arginine analogues, as substrates and measuring
      the rate of citrullination. The influence of gingipains on citrullination was
      assessed by measuring the rates of citrullination of bovine serum albumin in the
      presence of protease inhibitors. RESULTS: Enzyme activity decreased by 13%
      following exposure of cells to 60  degrees C for 10 min. A comparison of intact
      and disrupted cells indicated that 90% of PAD activity is cell surface associated
      and the remainder cytoplasmic. Optimal pH for enzyme activity was between pH 7.5
      and 8. All small arginine-containing peptides were citrullinated with reaction
      rates faster than that for free arginine with rates that varied with arginine
      residue position and number. Arginine analogues exhibited minimal effect and
      influence when tested as either substrates or competitive inhibitors. Cells were
      able to citrullinate yeast enolase, human vimentin and fibrin at varying rates.
      All proteins were modified at slower rates than those for peptide substrates.
      Inhibition of gingipains had no influence on the rate of protein citrullination.
      CONCLUSIONS: P. gingivalis PAD is a primarily cell surface associated, heat
      stable, enzyme that exhibits optimal activity under alkaline conditions similar
      to those present in the inflammatory environment. The enzyme displays high
      specificity for arginine residues in peptides and modified arginine in all
      positions and the gingipains did not influence the rate of protein
      citrullination. The ability of the enzyme to convert arginine residues in all
      proteins tested would indicate that its presence in inflamed tissue may promote
      autoimmune reactions by creation of altered host epitopes.

PMID- 23856044
TI  - Wnt and Rho GTPase signaling in osteoarthritis development and intervention:
      implications for diagnosis and therapy.
AB  - Wnt and Rho GTPase signaling play critical roles in governing numerous aspects of
      cell physiology, and have been shown to be involved in endochondral ossification
      and osteoarthritis (OA) development. In this review, current studies of canonical
      Wnt signaling in OA development, together with the differential roles of Rho
      GTPases in chondrocyte maturation and OA pathology are critically summarized.
      Based on the current scientific literature together with our preliminary results,
      the strategy of targeting Wnt and Rho GTPase for OA prognosis and therapy is
      suggested, which is instructive for clinical treatment of the disease. 

PMID- 23856046
TI  - Discovery, synthesis, and structure-activity relationships of 2-aminoquinazoline
      derivatives as a novel class of metabotropic glutamate receptor 5 negative
      allosteric modulators.
AB  - A virtual screening approach using various in silico methodologies led to the
      discovery of 2-(m-tolylamino)-7,8-dihydroquinazolin-5(6H)-one (1) as a moderately
      active negative allosteric modulator (NAM) of the metabotropic glutamate receptor
      subtype 5 (mGluR5) showing high selectivity against the subtype mGluR1.
      Modifications of the parent compound by rational design yielded a series of
      highly potent derivatives which will serve as valuable starting points for
      further hit-to-lead optimization efforts toward a suitable drug candidate for the
      treatment of L-DOPA induced dyskinesia.

PMID- 23856047
TI  - Tetrazole and triazole as bioisosteres of carboxylic acid: discovery of diketo
      tetrazoles and diketo triazoles as anti-HCV agents.
AB  - A series of diketo tetrazoles and diketo triazoles were designed and synthesized
      as bioisosteres of alpha,gamma-diketo acid, the active site inhibitor of HCV
      (Hepatitis C virus) polymerase NS5B. Among the synthesized compounds, 4-(4
      fluorobenzyloxy)phenyl diketo triazole (30) exhibited anti-HCV activity with an
      EC50 value of 3.9 MUM and an SI value more than 128. The reduction of viral
      protein and mRNA levels were also validated, supporting the anti-HCV activity of
      compound 30. These results provide convincing evidence that the diketo tetrazoles
      and diketo triazoles can be developed as bioisosteres of alpha,gamma-diketo acid
      to exhibit potent inhibitory activity against HCV.

PMID- 23856048
TI  - Quinolines derivatives as novel sunscreening agents.
AB  - Currently, the research and development of sunscreens play an important role on
      the synthesis of actives that are stable in various kinds of formulations-in
      addition to their efficiency and broad spectrum of protection against ultraviolet
      radiation. Our objective here was to synthesize new sunscreening chemical agents
      using quinoline as a base molecule. Twelve quinoline derivatives were
      synthesized, four of them novel molecules, and their photoprotective activity was
      determined in vitro using diffuse transmittance spectrophotometry. We determined
      their SPF, UVAPF, UVA/UVB ratio, critical wavelength and Boots Star Rating. The
      quinolines derivatives presented a varied profile of photoprotection, their SPF
      ranging from 2 to 11 and their UVAPF from 2 to 7. In terms of the critical
      wavelength, all molecules were considered of broad-spectrum by different
      classifications. Regarding the Boots Star Rating, one compound received no
      rating, seven of them received a three stars rating, three received a four stars
      rating and three were given a five stars rating. The molecules showed in the
      present work have a wide range of possibilities for creating new sunscreen
      products, once they have good SPF or UVAPF for single molecules, and they also
      possess other different qualities that can act synergistically. 

PMID- 23856049
TI  - Discovery of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1: optimization of
      kinase selectivity and pharmacokinetics.
AB  - The kinase selectivity and pharmacokinetic optimization of a series of 7
      aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. The intersection of
      insights from molecular modeling, computational prediction of metabolic sites,
      and in vitro metabolite identification studies resulted in a simple and unique
      solution to both of these problems. These efforts culminated in the discovery of
      compound 13a, a potent, relatively selective inhibitor of TAK1 with good
      pharmacokinetic properties in mice, which was active in an in vivo model of
      ovarian cancer. 

PMID- 23856050
TI  - Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side
      chromane-containing inhibitors.
AB  - The structure activity relationship of the prime region of conformationally
      restricted hydroxyethylamine (HEA) BACE inhibitors is described. Variation of the
      P1' region provided selectivity over Cat-D with a series of 2,2-dioxo
      isothiochromanes and optimization of the P2' substituent of chromane-HEA(s) with
      polar substituents provided improvements in the compound's in vitro permeability.
      Significant potency gains were observed with small aliphatic substituents such as
      methyl, n-propyl, and cyclopropyl when placed at the C-2 position of the
      chromane. 

PMID- 23856051
TI  - Are hERG channel blockers also phospholipidosis inducers?
AB  - Both pharmacophore models of the human ether-a-go-go-related gene (hERG) channel
      blockers and phospholipidosis (PLD) inducers contain a hydrophobic moiety and a
      hydrophilic motif/positively charged center, so it is interesting to investigate
      the overlap between the ligand chemical spaces of both targets. We have assayed
      over 4000 non-redundant drug-like compounds for both their hERG inhibitory
      activity and PLD inducing potential in a quantitative high throughput screening
      (qHTS) format. Seventy-seven percent of PLD inducing compounds identified from
      the screening were also found to be hERG channel blockers, and 96.9% of the
      dually active compounds were positively charged. Among the 48 compounds that
      induced PLD without inhibiting hERG channel, 24 compounds (50.0%) carried
      steroidal structures. According to our results, hERG channel blockers and PLD
      inducers share a large chemical space. In addition, a positively charged hERG
      channel blocker will most likely induce PLD, while a steroid PLD inducer is less
      likely a hERG channel blocker. 

PMID- 23856053
TI  - Ion mobility-mass spectrometry of intact protein--ligand complexes for
      pharmaceutical drug discovery and development.
AB  - Mass spectrometry (MS) plays a number of key roles in the discovery and
      development phases for modern pharmaceutical compounds, ranging from the
      assessment of protein-ligand binding to biomarker discovery. Historically,
      however, MS has had a relatively limited role in the drug discovery process in
      comparison to high-throughput fluorescence and radiometric screens. This picture
      may be changing, however, as many presumptive protein targets are coupled to
      human disease pathways through specific protein-protein interactions and protein
      conformations, rather than enzyme activities. This fact will likely drive the
      development of high-throughput analytical tools that put a stronger emphasis on
      the structural information content produced in a screen. Here we summarize recent
      developments surrounding ion mobility-mass spectrometry (IM-MS), one such MS
      based tool that is capable of rapidly measuring changes in protein structure,
      oligomeric state, and binding stoichiometry from complex mixtures at relatively
      low concentrations. 

PMID- 23856052
TI  - Delivery of Nox2-NADPH oxidase siRNA with polyketal nanoparticles for improving
      cardiac function following myocardial infarction.
AB  - Myocardial infarction (MI) is the most common cause of heart failure (HF), the
      leading cause of death in the developed world. Oxidative stress due to excessive
      production of reactive oxygen species (ROS) plays a key role in the pathogenesis
      of cardiac remodeling leading to HF. NADPH oxidase with Nox2 as the catalytic
      subunit is a major source for cardiac ROS production. Nox2-NADPH expression is
      significantly increased in the infarcted myocardium, primarily in neutrophils,
      macrophages and myocytes. Moreover, mice lacking the Nox2 gene are protected from
      ischemic injury, implicating Nox2 as a potential therapeutic target. RNAi
      mediated gene silencing holds great promise as a therapeutic owing to its high
      specificity and potency. However, in vivo delivery hurdles have limited its
      effective clinical use. Here, we demonstrate acid-degradable polyketal particles
      as delivery vehicles for Nox2-siRNA to the post-MI heart. In vitro, Nox2-siRNA
      particles are effectively taken up by macrophages and significantly knockdown
      Nox2 expression and activity. Following in vivo intramyocardial injection in
      experimental mice models of MI, Nox2-siRNA particles prevent upregulation of Nox2
      and significantly recovered cardiac function. This study highlights the potential
      of polyketals as siRNA delivery vehicles to the MI heart and represents a viable
      therapeutic approach for targeting oxidative stress.

PMID- 23856054
TI  - Echinomycin biosynthesis.
AB  - Echinomycin is an antitumor antibiotic secondary metabolite isolated from
      streptomycetes, whose core structure is biosynthesized by nonribosomal peptide
      synthetase (NRPS). The echinomycin biosynthetic pathway was successfully
      reconstituted in Escherichia coli. NRPS often contains a thioesterase domain at
      its C terminus for cyclorelease of the elongating peptide chain. Those
      thioesterase domains were shown to exhibit significant substrate tolerance. More
      recently, an oxidoreductase Ecm17, which forms the disulfide bridge in triostin
      A, was characterized. Surprisingly, an unrelated disulfide-forming enzyme GliT
      for gliotoxin biosynthesis was also able to catalyze the same reaction, providing
      another example of broad substrate specificity in secondary metabolite
      biosynthetic enzymes. Those promiscuous catalysts can be a valuable tool in
      generating diversity in natural products analogs we can produce heterologously. 

PMID- 23856055
TI  - Dot by dot: analyzing the glycome using lectin microarrays.
AB  - The glycome, that is, the cohort of carbohydrates within a cell or tissue, plays
      a key part in diverse biological interactions involved in health and disease.
      Glycans are structurally complex and notoriously difficult to analyze. Lectin
      microarrays, a sensitive and high-throughput method for glycomic profiling,
      provide a global view of the glycome. In recent work, this technology has been
      successfully applied to a wide range of studies, from identification of glycan
      based stem cell markers to the detection of pathogens and early diagnosis of
      disease. This review focuses on advances in the field of lectin microarrays. 

PMID- 23856056
TI  - Emerging trends in in vivo neurochemical monitoring by microdialysis.
AB  - Mapping chemical dynamics in the brain of live subjects is a challenging but
      highly rewarding goal because it allows neurotransmitter fluctuations to be
      related to behavior, drug effects, and disease states. A popular method for such
      measurements is microdialysis sampling coupled to analytical measurements. This
      method has become well-established for monitoring low molecular weight
      neurotransmitters, metabolites, and drugs, especially in pharmacological and
      pharmacokinetic studies. Recent technological developments which improve the
      temporal and spatial resolution of the methods will enable it to be used for
      studying behavior and small brain nuclei. Better assays allow monitoring more
      neurotransmitters simultaneously. Extension to analysis of aggregating proteins
      like amyloid beta is proving extremely useful for uncovering the roles of these
      molecules and how they contribute to neurodegenerative diseases. 

PMID- 23856057
TI  - Radical mediated ring formation in the biosynthesis of the hypermodified tRNA
      base wybutosine.
AB  - Wyosine and its derivatives are highly modified, acid labile tricyclic bases
      found at position 37 of tRNA(Phe) in archaea and eukarya. The formation of the
      common 4-demethylwyosine structural feature entails condensation of pyruvate and
      N-methylguanosine catalyzed by TYW1. This review will focus on the mechanism of
      this complex radical mediated transformation. 

PMID- 23856058
TI  - The path of lysine to pyrrolysine.
AB  - Pyrrolysine is the 22nd genetically encoded amino acid. For many years, its
      biosynthesis has been primarily a matter for conjecture. Recently, a pathway for
      the synthesis of pyrrolysine from two molecules of lysine was outlined in which a
      radical SAM enzyme acts as a lysine mutase to generate a methylated ornithine
      from lysine, which is then ligated to form an amide with the E-amine of a second
      lysine. Oxidation of the isopeptide gives rise to pyrrolysine. Mechanisms have
      been proposed for both the mutase and the ligase, and structures now exist for
      each, setting the stage for a more detailed understanding of how pyrrolysine is
      synthesized and functions in bacteria and archaea. 

PMID- 23856059
TI  - Severity profiles in patients diagnosed of benign prostatic hyperplasia in Spain.
AB  - OBJECTIVES: To analyse the severity profiles and progression criteria in patients
      diagnosed of benign prostatic hyperplasia (BPH) in urology clinics in Spain.
      MATERIAL AND METHODS: A multicentre observational epidemiological study conducted
      in Spain between May-November 2008. A representative sample of 392 urologist
      gathered socio-demographic, clinical and patient-centered data from three
      consecutive patients with new diagnostic of BPH in urology clinics. RESULTS: A
      total of 1.115 patients were evaluated. Mean age was 65.7 years old. Mean time
      from the onset of symptoms to diagnostic was 18,8 months. Mean IPSS score was
      17.2. 63 patients (5,7%) had mild symptoms; 670 (60,1%) had moderate symptoms
      with a mean IPSS score of 14.6 and 382 (34.3%) had severe symptoms with a mean
      IPSS score of 23.7. Mean PSA was 2.6 ng/ml and ultrasound measured prostatic
      volume was 49.2cc. A total of 713 (63,9%) patients met progression criteria (PSA
      >1.5 ng/ml and volume>30 cc). Symptoms severity was directly correlated with age,
      prostatic volume, PSA, presence of progression criteria and time from the onset
      of symptoms and inversely correlated with urine flow rate (P<.001). Progression
      criteria was directly correlated with age, symptoms severity and inversely with
      urine flow rate (P<.01). CONCLUSIONS: More than 90% of patients diagnosed of BPH
      in urology clinics in Spain had moderate to severe symptoms. Two thirds met
      progression criteria that correlate with age and severity of symptoms.

PMID- 23856060
TI  - A general microwave-assisted two-phase strategy for nanocrystals synthesis.
AB  - A general microwave-assisted two-phase strategy (MTS) has been developed for the
      synthesis of monodisperse inorganic nanocrystals (NCs). A series of metal oxides,
      ferrite, hydroxides, and metal sulfide NCs were synthesized by using water
      soluble metal salts. The obtained NCs were characterized by X-ray diffraction
      (XRD) and transmission electron microscopy (TEM). The composition, size, and
      shape of the NCs can be tuned by the types of precursors, the concentrations of
      metal ions, and the species of ligands. This protocol creates a new synthetic
      route, which may also be further extended to synthesize other nanomaterials,
      including alloy, noble metal, rare-earth fluorescent, etc. 

PMID- 23856061
TI  - Influence of graphene exfoliation on the properties of water-containing adlayers
      visualized by graphenes and scanning force microscopy.
AB  - Molecular adlayers on mica have been visualized previously by coating the sample
      with graphene and imaging it by scanning force microscopy. While it had been
      argued that this shows that ambient water on mica exhibits ice-like structures,
      recent apparently similar experiments indicate different behaviors. Here, we
      demonstrate that adhesive tapes, which are often used to mechanically exfoliate
      graphenes onto solid substrates, can lead to water-containing adlayers, which
      differ substantially from pure water layers. We exfoliated graphenes with the aid
      of different adhesive tapes and demonstrate that the results depend on the
      particular tape. Our results imply that structure and properties of confined
      water adlayers can be controlled by minor amounts of additives. 

PMID- 23856062
TI  - Proximal femoral replacement in the management of acute periprosthetic fractures
      of the hip: a competing risks survival analysis.
AB  - To examine the mortality and implant survivorship of proximal femoral replacement
      (PFR), revision total hip arthroplasty (REV) and open reduction internal fixation
      (ORIF) in the treatment of acute periprosthetic fractures of the proximal femur,
      we retrospectively reviewed 97 consecutive acute periprosthetic proximal femoral
      fractures from 2000 to 2010. Three groups were defined: PFR (n=21), REV (n=19),
      and ORIF (n=57). Outcome measures were all-cause mortality, implant failure, and
      reoperation. Competing Risks survival analysis of overall mortality during the
      mean 35-month follow-up showed no statistical difference between the three groups
      (P=0.65; 12 and 60 month mortality for PFR: 37%, 45%; REV: 16%, 46%; ORIF: 14%,
      100%). Implant survival was worse for the PFR group (P=0.03, 12 and 60-month
      implant failure rate for PFR: 5%, 39%; REV: 7%, 7%; ORIF 2%, 2%). We conclude
      that PFR as compared with REV or ORIF may have worse medium-term implant
      survival, primarily due to instability and dislocation.

PMID- 23856063
TI  - Continuing clopidogrel during elective total hip and knee arthroplasty:
      assessment of bleeding risk and adverse outcomes.
AB  - Limited research assessing risks of continued clopidogrel perioperatively in
      patients undergoing elective orthopedic procedures exists. Patients that
      underwent elective primary or revision total knee arthroplasty (TKA) or total hip
      arthroplasty (THA) from 2007 to 2012 while taking clopidogrel at the time of
      surgical evaluation were retrospectively identified. Patient demographics, last
      dose of clopidogrel, intraoperative blood loss, blood transfusion, and presence
      of 30-day adverse cardiac events (ACE) were collected. Of 142 patients meeting
      criteria, 24 (16.9%) patients remained on clopidogrel perioperatively. Patients
      that continued clopidogrel were more likely to receive a blood transfusion within
      24 hours of surgery (31.8% vs. 7.7%; P=0.004) and during hospitalization (37.5%
      vs. 15.3%; P=0.02), but the incidence of 30-day ACE was not significantly
      different. Continuation of clopidogrel perioperatively for elective THA or TKA
      should be carefully considered.

PMID- 23856064
TI  - Lymphoepithelial-like carcinoma of the parotid gland: a case report and a brief
      review of the western literature.
AB  - BACKGROUND: Primary lymphoepithelial-like carcinoma of the parotid gland is a
      rare tumour with an increased incidence among Eskimos and Orientals. In these
      populations, it is usually associated with Epstein-Barr virus. In Western
      countries, salivary gland lymphoepithelial-like carcinomas are uncommon and only
      14 cases have been described so far; among these, only five cases showed Epstein
      Barr virus positivity. CASE REPORT: A 45-year-old woman was admitted to Siena
      Hospital for evaluation of a pre-existent (2 years) painless and tender
      submandibular mass, rapidly enlarging since two months. On physical examination,
      a 2.5-cm mass was found in the right parotid. It was firm, mobile and non-tender.
      Laboratory data were within reference range. Nuclear magnetic resonance detected
      a 2,5*1,5*1-cm well-circumscribed mass in the deep lobe of the right parotid. A
      total right paroditectomy with dissection of a satellite lymph node was
      performed. On the basis of morphological, immunohistochemical and molecular
      biology findings, a diagnosis of stage II (according to TNM7) Epstein Barr-virus
      positive, undifferentiated lymphoepithelial-like carcinoma of the parotid gland
      was made. Twenty months after surgery the patient was free of disease.
      CONCLUSIONS: Further studies seem to be necessary to completely elucidate the
      oncogenic role of Epstein Barr-virus in these tumors, which have identical
      morphology but different prognosis and variable presence of the virus. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1260381551000616.

PMID- 23856066
TI  - Induction of retinal ganglion-like cells from fibroblasts by adenoviral gene
      delivery.
AB  - Central nervous system neurons fail to regenerate after birth, which greatly
      hampers the effective treatment of many neurodegenerative diseases. Neurons
      differentiated from induced pluripotent stem cells have been considered a
      possible option for cell-based therapies. Recent discoveries have revealed that
      fibroblasts can be directly converted into neurons without a transition through a
      pluripotent state. This approach might serve as a more efficient and convenient
      method for the cellular therapy of neurodegenerative diseases. Currently, several
      types of neurons have been directly generated from fibroblasts, including
      dopamine neurons, motor neurons and neural progenitor cells. In our study, by
      screening a series of candidate genes, we found that the adenovirus-mediated
      transduction of Ascl1, Brn3b and Ngn2 can directly convert mouse fibroblasts to
      retinal ganglion-like cells. The induced retinal ganglion-like cells co-express
      multiple retinal ganglion cell markers, and exhibit membrane properties of
      functional neurons. The reprogramming mediated by adenoviruses occurs much sooner
      than that mediated by lentiviruses. Furthermore, the induced retinal ganglion
      like cells that are produced via adenoviral gene delivery are free of exogenous
      gene integration. Retinal ganglion-like cells that are induced by adenoviruses
      demonstrate great potential applicability in clinical therapy and provide a novel
      platform for the research of retinal degenerative diseases. 

PMID- 23856067
TI  - Hematoma expansion in experimental intracerebral hemorrhage is not altered by
      peracute treatment with recombinant tissue plasminogen activator.
AB  - Recombinant tissue-type plasminogen activator (rt-PA) is the mainstay of acute
      stroke treatment and the only approved medical therapy so far. Because of its
      fibrinolytic action, it is presumed to aggravate intracerebral hemorrhage (ICH).
      Since clinical features do not discriminate between ischemic stroke and ICH,
      brain imaging is strictly required before the initiation of thrombolysis. A
      recent study has shown that rt-PA does not worsen (primary) ICH in two different
      experimental mouse models. Here, we further explored this surprising finding and
      examined hematoma expansion and long-term outcome after rt-PA treatment in a
      murine model of ICH. We induced ICH by collagenase injection into the right basal
      ganglia of C57BL/6 mice. At 30 min, 90 min or 4h after ICH induction,
      respectively, mice were treated with vehicle or 10mg/kg rt-PA. In parallel, we
      administered the vascular tracer Evans Blue (EB) and sacrificed the mice 2h after
      injection to assess EB extravasation as a marker of ongoing bleeding and rt-PA
      induced rebleeding. Additionally, we observed mice which were treated with
      vehicle or rt-PA 30 min after ICH induction for 72 h and quantified functional
      outcome and hematoma volume. EB extravasation was highest in the groups that were
      treated after 30 min and decreased thereafter according to a cessation of active
      bleeding. At all three time points covering the early phase of ICH, treatment
      with rt-PA did not increase EB extravasation. In the 72 h observation, there was
      also no difference in functional outcome and hematoma volume. In our experimental
      study, we were not able to demonstrate that peracute rt-PA treatment in (primary)
      ICH has detrimental effects on hematoma expansion, hematoma volume or functional
      outcome. This finding needs careful consideration in future translational
      studies.

PMID- 23856065
TI  - CRH receptor antagonism reverses the effect of social subordination upon central
      GABAA receptor binding in estradiol-treated ovariectomized female rhesus monkeys.
AB  - Persistent exposure to environmental stressors causes dysregulation of the limbic
      hypothalamic-pituitary-adrenal (LHPA) axis and alters GABAA receptor (GABAAR)
      levels throughout the brain. Social subordination in socially housed female
      rhesus results in distinctive stress-related physiological and behavioral
      phenotypes that are dependent on the ovarian hormone estradiol (E2). In the
      present study, we utilized ovariectomized adult female rhesus monkeys undergoing
      hormone replacement with E2 to test the hypothesis that the chronic psychosocial
      stress of subordination alters GABAAR binding potential (GABAAR BPND) in limbic
      regions implicated in emotional processing including the prefrontal cortex,
      temporal lobe (amygdala and hippocampus), and hypothalamus. Furthermore, we
      tested the hypothesis that peripheral administration of a corticotropin-releasing
      hormone (CRH) receptor antagonist (astressin B) would reverse the alterations in
      GABAAR binding within these regions in subordinate females. After subjects
      received astressin B or saline for three consecutive days, GABAAR BPND was
      determined by positron emission tomography (PET) using (18)F-flumazenil as a
      radioligand. T1-weighted structural magnetic resonance imaging scans were also
      acquired for PET scan co-registration, in order to perform a region of interest
      analysis using the pons as a reference region. Compared to socially dominant
      females, subordinate females exhibited increased GABAAR BPND in the prefrontal
      cortex but not in the temporal lobe or the hypothalamus. Administration of
      astressin B eliminated the status difference in GABAAR BPND in the prefrontal
      cortex, suggesting that the chronic stressor of social subordination modulates
      GABAergic tone via effects on CRH and the LHPA axis, at least in prefrontal
      regions. 

PMID- 23856068
TI  - Interleukin-1beta alters the sensitivity of cannabinoid CB1 receptors controlling
      glutamate transmission in the striatum.
AB  - Proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin
      1beta (IL1beta) regulate both excitatory and inhibitory synaptic transmission in
      the central nervous system. The interaction between IL1beta and endocannabinoid
      system (ECS) is also emerging, based on the evidence that IL1beta effects on
      striatal spontaneous excitatory and inhibitory postsynaptic currents are
      regulated by transient receptor potential vanilloid 1 (TRPV1) channels, members
      of the ECS. Furthermore, IL1beta has also been shown to control the sensitivity
      of cannabinoid CB1 receptors controlling GABA transmission (CB1Rs(GABA)) in the
      striatum. To better detail the synaptic action of IL1beta, and to clarify its
      complex interaction with the ECS, here we investigated the possible interplay
      between IL1beta and CB1Rs controlling glutamate transmission (CB1Rs(glu)), other
      critical elements of the ECS. Our results show that the sensitivity of CB1Rs(glu)
      is fully blocked in the presence of IL1beta in corticostriatal brain slices, and
      that the protein kinase C/TRPV1 pathway is involved in this effect. IL1beta
      failed to modulate the sensitivity of glutamate synapses to the stimulation of
      GABAB receptors. We also provided evidence that IL1beta-CB1Rs(GABA) but not
      IL1beta-CB1Rs(glu) interaction is under the control of the brain-derived
      neurotrophic factor (BDNF)/trkB signaling and of lipid raft composition, because
      BDNF gene partial deletion, pharmacological blockade of trkB and membrane
      cholesterol removal with methyl-beta-cyclodextrin all blocked IL1beta-mediated
      inhibition of CB1Rs(GABA) but left unaltered the sensitivity of CB1Rs(glu) to
      this cytokine. Our results provide further evidence that synaptic transmission
      and the ECS are regulated by IL1beta in the striatum. 

PMID- 23856069
TI  - Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N((i)Pr)CH2CH2OH] for R = Ph, Cy
      and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against
      MCF-7R breast cancer cells and cell death pathways.
AB  - The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1),
      Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the
      doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater
      potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human
      apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell
      apoptotic assays, intracellular reactive oxygen species (ROS) measurements and
      human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2
      and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1
      activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both
      the p53 and p73 genes. Compounds 1 and 3 activate NF-kappaB, and each inhibits
      topoisomerase I. 

PMID- 23856070
TI  - MD simulations suggest important surface differences between reconstituted and
      circulating spherical HDL.
AB  - Since spheroidal HDL particles (sHDL) are highly dynamic, molecular dynamics (MD)
      simulations are useful for obtaining structural models. Here we use MD to
      simulate sHDL with stoichiometries of reconstituted and circulating particles.
      The hydrophobic effect during simulations rapidly remodels discoidal HDL
      containing mixed lipids to sHDL containing a cholesteryl ester/triglyceride
      (CE/TG) core. We compare the results of simulations of previously characterized
      reconstituted sHDL particles containing two or three apoA-I created in the
      absence of phospholipid transfer protein (PLTP) with simulations of circulating
      human HDL containing two or three apoA-I without apoA-II. We find that
      circulating sHDL compared with reconstituted sHDL with the same number of apoA-I
      per particle contain approximately equal volumes of core lipid but significantly
      less surface lipid monolayers. We conclude that in vitro reconstituted sHDL
      particles contain kinetically trapped excess phospholipid and are less than ideal
      models for circulating sHDL particles. In the circulation, phospholipid transfer
      via PLTP decreases the ratio of phospholipid to apolipoprotein for all sHDL
      particles. Further, sHDL containing two or three apoA-I adapt to changes in
      surface area by condensation of common conformational motifs. These results
      represent an important step toward resolving the complicated issue of the protein
      and lipid stoichiometry of circulating HDL. 

PMID- 23856071
TI  - A qualitative study of carers' and professionals' views on the management of
      people with intellectual disability and epilepsy: a neglected population.
AB  - Little attention has been paid to the specific needs of people with intellectual
      disability and epilepsy despite evidence of increased prevalence of epilepsy,
      increased risk of complex epilepsy, and heightened use of health services among
      this group. In an attempt to address this gap, an online international survey was
      undertaken inviting health professionals and caregivers, both paid and family
      members, to share their views on the adequacy and quality of available treatment.
      This paper reports on the responses obtained from 113 individuals from the UK and
      Ireland. Findings revealed that professionals and carers differ in their
      expectations of treatment and with regard to maximizing communication during
      consultations. In addition, findings suggested that the potential of
      consultations to provide information for carers, as well as to allay concerns,
      may not be realized. Rescue medications were viewed favorably; however,
      respondents expressed less satisfaction with routine medications. These findings
      may reflect a failure by professionals to appropriately transfer knowledge of
      these treatments. 

PMID- 23856072
TI  - The relationship between sexual violence and human immunodeficiency virus (HIV)
      infection among women using voluntary counseling and testing services in South
      Wollo Zone, Ethiopia.
AB  - BACKGROUND: Gender based violence affects the health and wellbeing of women
      across the world on an epidemic scale. While women remain more vulnerable to both
      sexual violence and risk of HIV infection, they are less able to access health
      and other welfare services than men. These vulnerabilities are further compounded
      by social factors, including the low status of women in many communities and
      their lack of decision-making power, both within the household and in wider
      society. The objective of this study was to assess the relationship between
      sexual violence and HIV infection among clients of voluntary counseling and
      testing (VCT) services in South Wollo Zone, Ethiopia. METHODOLOGY: A facility
      based cross sectional study was conducted using quantitative methods on a sample
      of 647 people living in seven selected districts of South Wollo Zone, Amhara
      Regional State. RESULTS: The study revealed that sexual violence is significantly
      associated with the risk of HIV infection. The prevalence of lifetime sexual
      violence, lifetime partner violence, and last 12 months partner violence were
      34.6%, 32.3% and 10.5% respectively. Both partner violence and lifetime sexual
      violence by another perpetrator were associated with HIV. The overall prevalence
      of HIV among VCT users was 21.5%. Both before (crude analysis) and after the
      results were adjusted for selected variables, women who experienced sexual
      violence in the last 12 months by their intimate partner or by another
      perpetrator is significantly associated with their HIV status. The chances of
      having HIV was 1.97 times higher among women victims who have a history of
      lifetime partner violence when compared with women who are not victims; crude
      odds ratio (COR) = 1.97, 95% Confidence Interval (CI), (1.34 - 2.90). CONCLUSION:
      The study revealed that sexual violence is significantly associated with the risk
      of HIV infection. Empowerment of women can be used as an important tool to reduce
      both sexual violence and HIV. More importantly policy issues must be set by all
      actors to take action on the mediating variables that interacted with violence to
      aggravate the transmission of HIV.

PMID- 23856073
TI  - Absence of a 'smoker's paradox' in field triaged ST-elevation myocardial
      infarction patients undergoing percutaneous coronary intervention.
AB  - PURPOSE: The 'smoker's paradox' refers to the observation of favorable prognosis
      in current smokers following an acute myocardial infarction (AMI). Initial
      positive findings were in the era of fibrinolysis, with more contemporary studies
      finding conflicting results. We sought to determine the presence of a 'smoker's
      paradox' in a cohort of ST Elevation Myocardial Infarction (STEMI) patients
      identified via field triage, treated with primary percutaneous coronary
      intervention (pPCI). METHODS: This was a single center retrospective cohort study
      identifying consecutive STEMI patients presenting for pPCI via field triage. The
      primary end points were all cause mortality, major adverse cardiac events (MACE),
      major bleeding, in-hospital cardiac arrest and length of stay (LOS). RESULTS: A
      total of 382 patients were included in the study. Current smokers were more
      likely to be younger (p<0.00001), male (p<0.001) and have fewer comorbidities,
      including renal impairment (p<0.01) and a history of AMI (p<0.05). Current
      smokers also had a shorter ischemic time (p<0.05), were less likely to have
      collateral circulation (p<0.05), and more likely to have signs of pulmonary edema
      at presentation (p<0.05). There was no difference between smoking groups and all
      cause mortality (p=0.67), MACE (p=0.49), major bleeding (p=0.49) or in-hospital
      cardiac arrest (p=0.43). Current smokers had a shorter LOS (p<0.05). In
      multivariate analysis smoking status did not correlate with primary outcomes.
      CONCLUSION: The 'smoker's paradox' does not appear to be relevant among STEMI
      patients undergoing pPCI, identified via field triage. The previously documented
      'smoker's paradox' may have been an indication of patient characteristics and the
      historical treatment of STEMI with thrombolysis. Further studies with larger
      numbers may be warranted.

PMID- 23856074
TI  - Oral administration of a gemini vitamin D analog, a synthetic triterpenoid and
      the combination prevents mammary tumorigenesis driven by ErbB2 overexpression.
AB  - HER2 (or ErbB2), a member of ErbB receptor tyrosine kinases, is overexpressed in
      approximately 20% of human breast cancer, and the ErbB2 signaling pathway is a
      critical therapeutic target for ErbB2-overexpressing breast cancer. We
      investigated the inhibitory effects of the Gemini vitamin D analog BXL0124, the
      synthetic triterpenoid CDDO-Im and the combination on the tumorigenesis of ErbB2
      overexpressing breast cancer. MMTV-ErbB2/neu transgenic mice were treated with
      BXL0124, CDDO-Im, or the combination from three months of age until the end of
      the experiment. Formation and growth of MMTV-ErbB2/neu mammary tumors were
      monitored every week, and all three treatments delayed the development of mammary
      tumors without significant toxicity. Decreased activation of ErbB2 as well as
      other ErbB receptors, ErbB1 and ErbB3, in MMTV-ErbB2/neu mammary tumors was shown
      by all treatments. Protein levels of downstream targets of the ErbB2 signaling
      pathway, including activated-Erk1/2, activated-Akt, c-Myc, CycD1, and Bcl2, were
      repressed by all three treatments, with the combination treatment exhibiting the
      strongest effects. To investigate therapeutic efficacy, the combination of
      BXL0124 and CDDO-Im was given to MMTV-ErbB2/neu mice after mammary tumors were
      established between 23 and 30 weeks of age. Short-term treatment with the
      combination did not show effects on tumor growth nor the ErbB2 signaling pathway.
      The present study shows BXL0124, CDDO-Im, and the combination as potential agents
      for prevention, but not treatment, against the tumorigenesis of ErbB2
      overexpressing breast cancer.

PMID- 23856075
TI  - Predicting carcinogenicity of diverse chemicals using probabilistic neural
      network modeling approaches.
AB  - Robust global models capable of discriminating positive and non-positive
      carcinogens; and predicting carcinogenic potency of chemicals in rodents were
      developed. The dataset of 834 structurally diverse chemicals extracted from
      Carcinogenic Potency Database (CPDB) was used which contained 466 positive and
      368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors
      were derived. Structural diversity of the chemicals and nonlinearity in the data
      were evaluated using Tanimoto similarity index and Brock-Dechert-Scheinkman
      statistics. Probabilistic neural network (PNN) and generalized regression neural
      network (GRNN) models were constructed for classification and function
      optimization problems using the carcinogenicity end point in rat. Validation of
      the models was performed using the internal and external procedures employing a
      wide series of statistical checks. PNN constructed using five descriptors
      rendered classification accuracy of 92.09% in complete rat data. The PNN model
      rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster
      and pesticide data, respectively. The GRNN constructed with nine descriptors
      yielded correlation coefficient of 0.896 between the measured and predicted
      carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data.
      The rat carcinogenicity model (GRNN) applied to the mouse and hamster data
      yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46,
      respectively. The results suggest for wide applicability of the inter-species
      models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN
      (inter-species) models constructed here can be useful tools in predicting the
      carcinogenicity of new chemicals for regulatory purposes. 

PMID- 23856076
TI  - Face perception is category-specific: evidence from normal body perception in
      acquired prosopagnosia.
AB  - Does the human visual system contain perceptual mechanisms specialized for
      particular object categories such as faces? This question lies at the heart of a
      long-running debate in face perception. The face-specific hypothesis posits that
      face perception relies on mechanisms dedicated to faces, while the expertise
      hypothesis proposes that faces are processed by more generic mechanisms that
      operate on objects we have extended experience with. Previous studies that have
      addressed this question using acquired prosopagnosia are inconclusive because the
      non-face categories tested (e.g., cars) were not well-matched to faces in terms
      of visual exposure and perceptual experience. Here we compare perception of faces
      and bodies in four acquired prosopagnosics. Critically, we used face and body
      tasks that generate comparable inversion effects in controls, which indicates
      that our tasks engage orientation-specific perceptual mechanisms for faces and
      bodies to a similar extent. Three prosopagnosics were able to discriminate bodies
      normally despite their impairment in face perception. Moreover, they exhibited
      normal inversion effects for bodies, suggesting their body perception was carried
      out by the same mechanisms used by controls. Our findings indicate that the human
      visual system contains processes specialized for faces.

PMID- 23856077
TI  - What autoantibody tests should become widely available to help scleroderma
      diagnosis and management?
AB  - Anti-Th/To autoantibodies have been recognized as serological markers of systemic
      sclerosis (SSc) for more than 20 years. However, validated immunoassay kits to
      test this specificity have not been commercially available. SSc autoantibodies
      are basically mutually exclusive and are associated with a certain subset of the
      disease and/or with organ involvement. Anti-Th/To are generally considered to be
      markers of the limited cutaneous type of SSc with the involvement of certain
      internal organs. The excellent correlation between anti-Rpp25 as detected by
      their novel chemiluminescent method and anti-Th/To as detected by
      immunoprecipitation suggest that the new assays may become widely available tests
      for clinicians in future and could help to clarify the clinical significance of
      anti-Th/To in SSc as well as other conditions over different races or countries. 

PMID- 23856078
TI  - Cord blood-derived and peripheral blood-derived cytokine-induced killer cells are
      sensitive to Fas-mediated apoptosis.
AB  - Fas-mediated apoptosis is one of the mechanisms used by tumor cells to escape the
      cytotoxicity of tumor-infiltrating lymphocytes. It has been suggested that
      cytokine-induced killer (CIK) cells are resistant to Fas-mediated apoptosis,
      thereby rendering them more attractive for use in cellular immunotherapy. Unlike
      what was observed by others, here we show that CIK cells are sensitive to Fas
      mediated apoptosis. We have observed an increase in Fas expression in the
      different CIK cell subpopulations (CD3(+)CD56(-), CD3(+)CD56(+), and CD3(
      )CD56(+)) isolated from both cord blood (CB) and peripheral blood (PB). We also
      show that the bulk, as well as the CD3(+)CD56(-) and CD56(+) CB- and PB-CIK cell
      subpopulations were sensitive to Fas-mediated apoptosis induced by both CH11 and
      APO-1 antibodies, albeit with a weaker effect for the CH11 antibody on CB-CIK
      cells. In addition, in the presence of the APO-1 and CH11 inducers, Fas
      engagement inhibited the cytotoxic activity of CB- and PB-CIK cells. This new
      contradictory result may help explain the variable efficacy observed with CIK
      cells in the clinic.

PMID- 23856079
TI  - Steroids in Duchenne muscular dystrophy.

PMID- 23856080
TI  - Root border cells and secretions as critical elements in plant host defense.
AB  - Border cells and border-like cells are released from the root tip as individual
      cells and small aggregates, or as a group of attached cells. These are viable
      components of the root system that play a key role in controlling root
      interaction with living microbes of the rhizosphere. As their separation from
      root tip proceeds, the cells synthesize and secrete a hydrated mucilage that
      contains polysaccharides, secondary metabolites, antimicrobial proteins and
      extracellular DNA (exDNA). This exDNA-based matrix seems to function in root
      defense in a way similar to that of recently characterized neutrophil
      extracellular traps (NETs) in mammalian cells. This review discusses the role of
      the cells and secreted compounds in the protection of root tip against microbial
      infections. 

PMID- 23856081
TI  - The PRR family of transcriptional regulators reflects the complexity and
      evolution of plant circadian clocks.
AB  - Circadian clocks are internal time-keeping mechanisms that provide an adaptive
      advantage by enabling organisms to anticipate daily changes and orchestrate
      biological processes accordingly. Circadian regulated pseudo-response regulators
      are key components of transcription/translation circadian networks in green alga
      and plants. Recent studies in Arabidopsis thaliana have shown that most of them
      act as transcriptional repressors and directly regulate output pathways
      suggesting a close relationship between the central oscillator and circadian
      regulated processes. Moreover, phylogenetic studies on this small gene family
      have shed light on the evolution of circadian clocks in the green lineage. 

PMID- 23856082
TI  - Modulation of plant immunity by light, circadian rhythm, and temperature.
AB  - Plants perceive and integrate intrinsic and extrinsic signals to execute
      appropriate responses for maximal survival and reproductive success. Plant immune
      responses are tightly controlled to ensure effective defenses against pathogens
      while minimizing their adverse effects on plant growth and development. Plant
      defenses induced in response to pathogen infection are modulated by abiotic
      signals such as light, circadian rhythm, and temperature. The modulation occurs
      on specific key components of plant immunity, indicating an intricate integration
      of biotic and abiotic signals. This review will summarize very recent studies
      revealing the intersection of plant defenses with light, circadian rhythm and
      temperature. In addition, it will discuss the adaptive value and evolutionary
      constraints of abiotic regulation of plant immunity. 

PMID- 23856083
TI  - The relationship of chronic medical illnesses, poor health-related lifestyle
      choices, and health care utilization to recovery status in borderline patients
      over a decade of prospective follow-up.
AB  - BACKGROUND: The interaction of borderline personality disorder (BPD) with
      physical health has not been well characterized. In this longitudinal study, we
      investigated the long-term relationship of chronic medical illnesses, health
      related lifestyle choices, and health services utilization to recovery status in
      borderline patients over a decade of prospective follow-up. METHOD: 264
      borderline patients were interviewed concerning their physical health at 6-year
      follow-up in a longitudinal study of the course of BPD. This sample was then
      reinterviewed five times at two-year intervals over the next ten years. We
      defined recovery from BPD based on a Global Assessment of Functioning score of 61
      or higher, which required BPD remission, one close relationship, and full-time
      competent and consistent work or school attendance. We controlled for potentially
      confounding effects of time-varying major depressive disorder. RESULTS: Never
      recovered borderline patients were significantly more likely than ever-recovered
      borderline patients to have a medical syndrome, obesity, osteoarthritis,
      diabetes, urinary incontinence, or multiple medical conditions (p<0.0063). They
      were also significantly more likely to report pack-per-day smoking, weekly
      alcohol use, no regular exercise, daily sleep medication use, or pain medication
      overuse (p<0.0083). In addition, never-recovered borderline patients were
      significantly more likely than ever-recovered borderline patients to undergo a
      medical emergency room visit, medical hospitalization, X-ray, CT scan, or MRI
      scan (p<0.0063). CONCLUSIONS: Over a decade of prospective follow-up, failure to
      recover from BPD seems to be associated with a heightened risk of chronic medical
      illnesses, poor health-related lifestyle choices, and costly health services
      utilization.

PMID- 23856084
TI  - Breast cancer in patients with schizophrenia.
AB  - BACKGROUND: Schizophrenia has a powerful impact on the outcomes of treatment for
      physical disorders. This study sought to estimate how the presence of
      schizophrenia disrupts the course of diagnosis and initial treatment of breast
      cancer. METHODS: We searched the Patient Treatment File, a comprehensive computer
      based system for inpatient data in the Department of Veterans Affairs (DVA)
      medical system, to identify patients with codes for schizophrenia or
      schizoaffective disorder who later developed breast cancer. These data were
      augmented with chart-based clinical data. RESULTS: There were 56 evaluable
      patients from 34 DVA facilities; 37 (66%) were female. Delay in diagnosis was
      common. The mean size of the primary tumor was 4 cm in those for whom these data
      were recorded. Delay in diagnosis was common and many never received the
      indicated surgery. Distant metastases were present on diagnosis in 12 (21%) and
      developed after diagnosis in 14 (25%) others, including 7 who inappropriately
      delayed or refused indicated surgery and 4 who inappropriately delayed or refused
      indicated neoadjuvant chemotherapy. Twelve verbally abused or physically attacked
      caregivers. CONCLUSIONS: Patients with schizophrenia who later develop breast
      cancer often deny they have cancer. They often have high-stage disease at
      diagnosis and often delay or refuse therapy. Breast-conserving multimodality
      therapy is often not feasible.

PMID- 23856085
TI  - Peritoneal dialysis catheter embedment: surgical considerations, expectations,
      and complications.
AB  - BACKGROUND: Peritoneal dialysis catheter embedment consists of implanting the
      catheter far in advance of anticipated need, with the external tubing buried
      under the skin. The catheter is externalized when initiation of dialysis is
      required. Details of the surgical procedure and management of associated
      complications are generally lacking. METHODS: A total of 84 catheters including
      conventional and extended catheters were embedded and externalized during the
      study period. Factors influencing duration of embedment, functionality upon
      externalization, and long-term outcomes were analyzed. RESULTS: Mean duration of
      embedment was 13.9 months (median 9.4; range .5 to 68.5). Immediate function was
      exhibited in 85.7% of catheters. Employing laparoscopic revision, 98.8% of
      embedded catheters were successfully used for peritoneal dialysis. Extended
      catheters and duration of embedment were important determinants of catheter
      functionality. CONCLUSIONS: Catheters can be embedded for prolonged periods and
      still result in functional dialysis access when needed. Complications are few and
      easily managed.

PMID- 23856086
TI  - Health-related quality of life changes following major and minor hepatic
      resection: the impact of complications and postoperative anemia.
AB  - BACKGROUND: Few studies have evaluated the health-related quality-of-life (QOL)
      changes in patients following major liver resection for malignancy. METHODS: QOL
      parameters were recorded prospectively at baseline (preoperative), and through 6
      months of follow-up using various instruments. RESULTS: Major complications
      occurred in 10 of 41 patients. At the initial outpatient visit, patients reported
      decreased global QOL with increased fatigue compared with baseline, which
      normalized at 6 weeks' follow-up and remained stable at 6 months. Those with
      major complications reported increased severity of pain over baseline at initial
      follow-up and at 6 months. Patients anemic at the time of discharge had worse
      physical QOL at 6 weeks, but levels similar to nonanemic patients at 3 months.
      CONCLUSIONS: Major complications are associated with increased reporting of pain
      persisting at 6 months. Attention to pain control, especially among patients with
      major complications, may improve QOL after major hepatic resection.

PMID- 23856087
TI  - Incidence and risk factors of chylous ascites after colorectal cancer surgery.
AB  - BACKGROUND: The aim of this study was to identify possible risk factors
      associated with chylous ascites after colorectal cancer surgery. METHODS:
      Patients who underwent colorectal cancer resection were enrolled in this study.
      Data were compared between patients who developed chylous ascites and those who
      did not. RESULTS: Chylous ascites was detected in 48 (6.6%) patients. There were
      significant differences between the groups with and without chylous ascites in
      terms of age (65.6 vs 61.6 years, P = .017), operator (5.0% vs 15.5%, P < .001),
      operative procedure based on tumor location (P = .041), operative time (206.0 vs
      229.8 minutes, P = .045), and blood loss (78.1 vs 219.7 mL, P = .036). After
      subgroup analysis for right-sided colectomy and low anterior resection to
      compensate for the effects of the operative procedure, the differences in the
      operative time and blood loss were not significant. In most patients, chylous
      ascites was resolved with conservative management. CONCLUSIONS: Chylous ascites
      developed significantly more frequently in patients who underwent right-sided
      colectomy and in elderly patients. In addition, the incidence was also dependent
      on the operator. Conservative treatment was effective in most patients.

PMID- 23856088
TI  - [Endoscopic extraction of a foreign body in the sigmoid colon].

PMID- 23856089
TI  - Critical evaluation of a new passive exchange-meter for assessing multimedia fate
      of persistent organic pollutants at the air-soil interface.
AB  - A new passive exchange meter (PEM) to measure inter-compartment fluxes of
      persistent organic pollutants (POPs) at the interface between soil and the
      atmosphere is described. The PEM uses labeled reference compounds (RC) added in
      situ to vegetation litter deployed in open cylinders designed to trap the
      vertical downward export of the RCs while allowing free exchange of POPs between
      litter and air. Fluxes of native compounds (bulk deposition, volatilization and
      downward export) are quantitatively tracked. One scope of the PEM is to
      investigate the influence of biogeochemical controls on contaminant re
      mobilization. The PEM performance was tested in a subtropical forest by comparing
      measurements under dense canopy and in a canopy gap; conditions in which
      deposition and turn-over of organic matter (OM) occur at different rates.
      Significant differences in fate processes were successfully detected.
      Surprisingly, mobilization by leaching of more hydrophobic compounds was higher
      under canopy, possibly as a result of canopy mediated enhancement of OM
      degradation. 

PMID- 23856090
TI  - New steroids and sesquiterpene from Turraea pubescens.
AB  - Four new compounds, including three new steroids (1-3) and one new sesquiterpene
      (6), and two new natural products (4-5), as well as three known steroids (7-9)
      were isolated from the twigs of Turraea pubescens. Compounds 3-5 are C22 steroids
      isolated from the Meliaceae family for the first time. Their structures were
      elucidated by extensive NMR and MS analyses. Compound 1 exhibited inhibitory
      activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in
      RAW264.7 cells with an IC50 value of 11.5 MUM.

PMID- 23856091
TI  - The protective activity of imperatorin in cultured neural cells exposed to
      hypoxia re-oxygenation injury via anti-apoptosis.
AB  - Apoptosis is believed to play important roles in neuronal cell death associated
      with cerebral ischemia. We now provided evidence that imperatorin (IMp), the main
      composition of the dried root or rhizome of R Radix Angelicae Dahuricae, took
      advantage on oxygen glucose deprivated/reperfusion (OGD-R) SH-SY5Y cell line
      through neuronal apoptosis inhibition. Our data had shown that imperatorin
      reduced the number of apoptosis cells after OGD-R, this effect was associated
      with the inhibition of the apoptosis factors Bax and caspase-3, and the
      upregulation of anti-apoptosis factor Bcl-2. In the meantime, the protective
      factor BDNF was upregulated significantly by imperatorin treatment. In our
      experiment in vivo, imperatorin decreased the infract volume significantly in
      dose of 5 mg/kg and 10 mg/kg, and the behavior ability was increased in the
      10mg/kg of imperatorin. Our observations show that imperatorin exerted protective
      effect on cerebral ischemia both in vitro and in vivo, this effect is associated
      with its anti-apoptosis function.

PMID- 23856092
TI  - alpha-Glucosidase inhibitory triterpenoids from the stem barks of Uncaria
      laevigata.
AB  - A phytochemical study on the ethanolic extract of the stem barks of Uncaria
      laevigata leads to the isolation and characterization of 18 triterpenoid
      compounds. Ten of these are new, including one novel heptanortriterpenoid (1),
      four ursane triterpenes (2-4, 10), and five oleanane triterpenes (5-9). Their
      structures were established by spectroscopic methods, especially by 2D-NMR and MS
      analyses. All these isolates were evaluated for their inhibitory effects on alpha
      glucosidase: ursolic acid and 3 showed potent activities with IC50 values of 16
      +/- 2.2 and 49 +/- 3.7 MUM, respectively.

PMID- 23856093
TI  - VAV1 represses E-cadherin expression through the transactivation of Snail and
      Slug: a potential mechanism for aberrant epithelial to mesenchymal transition in
      human epithelial ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecological malignancy in the western world.
      Although patients with early-stage ovarian cancer generally have a good
      prognosis, approximately 20%-30% of patients will die of the disease, and 5-year
      recurrence rates are 25%-45%, highlighting the need for improved detection and
      treatment. We investigated the role of VAV1, a protein with guanine nucleotide
      exchange factor activity, which is associated with survival in patients with
      early-stage ovarian cancer (International of Obstetrics and Gynecology [FIGO]
      stages I and II). We analyzed 88 samples from patients with primary epithelial
      ovarian cancer, which were divided into FIGO stages I and II (n = 46), and III
      and IV (n = 42). Prognostic analysis revealed that upregulated VAV1 expression
      correlated significantly with poor prognosis in patients with early-stage
      epithelial ovarian cancer (P <= 0.05), but not with other clinicopathologic
      features. Stable overexpression of VAV1 in human high-grade serous ovarian cancer
      SKOV3 cells induced morphologic changes indicative of loss of intercellular
      adhesions and organized actin stress fibers. Western blotting and real-time
      reverse transcriptase-polymerase chain reaction demonstrated that these cells had
      downregulated E-cadherin protein and messenger RNA levels, respectively. This
      downregulation is associated with epithelial-mesenchymal transition (EMT) and
      invasive cancer. Furthermore, VAV1 overexpression in both SKOV3 and human ovarian
      surface epithelial cells demonstrated that its upregulation of an E-cadherin
      transcriptional repressor, Snail and Slug, was not confined to ovarian cancer
      cells. Conversely, knockdown of VAV1 by RNA interference reduced Snail and Slug.
      Our findings suggest that VAV1 may play a role in the EMT of ovarian cancer, and
      may serve as a potential therapeutic target.

PMID- 23856096
TI  - A new Italian questionnaire to assess caregivers of cancer patients' satisfaction
      with palliative care: multicenter validation of the post mortem questionnaire
      short form.
AB  - CONTEXT: Caregiver satisfaction with palliative care is a crucial indicator of
      its effectiveness. In light of the lack of validated or reliable Italian
      instruments, the Post Mortem Questionnaire-Short Form (QPM-SF), a self-report
      questionnaire, has been developed to assess home and inpatient hospice care.
      OBJECTIVES: The present study was designed to evaluate the psychometric
      properties of QPM-SF and assess for differences in quality of palliative care
      between hospice and home care settings. METHODS: A total of 584 caregivers of
      terminal cancer patients completed QPM-SF one month after the death of the care
      recipient. To assess test-retest reliability, a subgroup of 50 caregivers
      completed the questionnaire a second time, one month later. RESULTS: QPM-SF
      showed good internal consistency and temporal stability and a four-factor
      structure: "Integrated home care," "Hospice," "Physical care-Information-Global
      evaluation," and "Needs." CONCLUSION: QPM-SF may be considered a valid, reliable,
      and well-accepted self-report instrument for examining and implementing
      palliative care interventions.

PMID- 23856095
TI  - The role of a low-dose ketamine-midazolam regimen in the management of severe
      painful crisis in patients with sickle cell disease.
AB  - CONTEXT: Acute pain is one of the main causes of hospital admission in sickle
      cell disease, with variable intensity and unpredictable onset and duration.
      OBJECTIVES: We studied the role of a low-dose intravenous (IV) ketamine-midazolam
      combination in the management of severe painful sickle cell crisis. METHODS: A
      retrospective analysis was performed with data from nine adult patients who were
      admitted to the intensive care unit with severe painful sickle cell crises not
      responding to high doses of IV morphine and other adjuvant analgesics. A ketamine
      midazolam regimen was added to the ongoing opioids as an initial bolus of
      ketamine 0.25mg/kg, followed by infusion of 0.2-0.25mg/kg/h. A midazolam bolus of
      1mg followed by infusion of 0.5-1mg/h was added to reduce ketamine emergence
      reactions. Reduction in morphine daily requirements and improvement in pain
      scores were the determinants of ketamine-midazolam effect. The t-tests were used
      for statistical analysis. RESULTS: Nine patients were assessed, with mean age of
      27+/-11 years. Morphine requirement was significantly lower after adding the IV
      ketamine-midazolam regimen. The mean+/-SD IV morphine requirement (milligram/day)
      in the pre-ketamine day (D0) was 145.6+/-16.5, and it was 112+/-12.2 on Day 1
      (D1) of ketamine treatment (P=0.007). The Numeric Rating Scale scores on D0
      ranged from eight to ten (mean 9.1), but improved to range from five to seven
      (mean 5.7) on D1. There was a significant improvement in pain scores after adding
      ketamine-midazolam regimen (P=0.01). CONCLUSION: Low-dose ketamine-midazolam IV
      infusion might be effective in reducing pain and opioid requirements in patients
      with sickle cell disease with severe painful crisis. Further controlled studies
      are required to prove this effect.

PMID- 23856094
TI  - Thyroid nodule as a first manifestation of Hodgkin lymphoma-report of two cases
      and literature review.
AB  - Lymphomas account for less than 5% of thyroid malignant lesions. Vast majority of
      them are B-cell non-Hodgkin lymphomas (NHL), while Hodgkin lymphoma (HL) is
      extremely rare. Here we present two cases of HL, at baseline manifesting as a
      thyroid lesion. First patient, 29-year-old pregnant female, initially suspected
      for metastatic medullary thyroid cancer, was eventually diagnosed with mixed
      cellularity type of thyroid HL. Second patient, 22-year-old woman with suspicion
      of advanced thyroid cancer, was in the end diagnosed with an extra-lymphatic
      classical HL of the thyroid. In both cases, despite repeated fine-needle
      aspiration biopsy, cytological examination gave inconclusive or misleading
      results. On histopathological examination, thyroid tumor cells were positive for
      CD15 and CD30 antigen, which is typical for Reed-Sternberg cells. In the report
      authors also discuss difficulties in management as well as potential importance
      of novel methods such as FISH, PCR and other molecular techniques in diagnostics
      of thyroid lymphomas. VIRTUAL SLIDES: The virtual slide(s) for this article can
      be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2896947559559648.

PMID- 23856097
TI  - Predictive factors for do-not-resuscitate designation among terminally ill cancer
      patients receiving care from a palliative care consultation service.
AB  - CONTEXT: Since the development of palliative care in the 1980s, "do not
      resuscitate" (DNR) has been promoted worldwide to avoid unnecessary resuscitation
      in terminally ill cancer patients. OBJECTIVES: This study aimed to evaluate the
      effect of a palliative care consultation service (PCCS) on DNR designation and to
      identify a subgroup of patients who would potentially benefit from care by the
      PCCS with respect to DNR designation. METHODS: In total, 2995 terminally ill
      cancer patients (with a predicted life expectancy of less than six months by
      clinician estimate) who received care by the PCCS between January 2006 and
      December 2010 at a single medical center in Taiwan were selected. Among these,
      the characteristics of 2020 (67.4%) patients who were not designated as DNR at
      the beginning of care by the PCCS were retrospectively analyzed to identify
      variables pertinent to DNR designation. RESULTS: A total of 1301 (64%) of 2020
      patients were designated as DNR at the end of care by the PCCS. Male gender and
      primary liver cancer were characteristics more predominantly found among DNR
      designated patients who also had worse performance status, higher prevalence of
      physical distress, and shorter intervals from palliative care referral to death
      than did patients without DNR designation. On univariate analysis, a higher
      probability of DNR designation was associated with male gender, duration of care
      by the PCCS of more than 14 days, patients' prognostic awareness, family's
      diagnostic and prognostic awareness, and high Palliative Prognostic Index (PPI)
      scores. On multivariate analysis, duration of care by the PCCS, patients'
      prognostic awareness, family's diagnostic and prognostic awareness, and a high
      PPI score constituted independent variables predicting DNR-designated patients at
      the end of care by the PCCS. CONCLUSION: DNR designation was late in terminally
      ill cancer patients. DNR-designated cancer patient indicators were high PPI
      scores, patients' prognostic awareness, family's diagnostic and prognostic
      awareness, and longer durations of care by the PCCS.

PMID- 23856098
TI  - Development and testing of a computerized pain body map in patients with advanced
      cancer.
AB  - CONTEXT: Pain localization is an important part of pain assessment. Development
      of pain tools for self-report should include expert and patient input, and
      patient testing in large samples. OBJECTIVES: To develop a computerized pain body
      map (CPBM) for use in patients with advanced cancer. METHODS: Three studies were
      conducted: 1) an international expert survey and a pilot study guiding the
      contents and layout of the CPBM, 2) clinical testing in an international symptom
      assessment study in eight countries and 17 centers (N = 533), and 3) comparing
      patient pain markings on computer and paper body maps (N = 92). RESULTS: Study 1:
      22 pain experts and 28 patients participated. A CPBM with anterior and posterior
      whole body views was developed for marking pain locations, supplemented by pain
      intensity ratings for each location. Study 2: 533 patients (286 male, 247 female,
      mean age 62 years) participated; 80% received pain medication and 81% had
      metastatic disease. Eighty-five percent completed CPBM as intended. Mean +/- SD
      number of marked pain locations was 1.8 +/- 1.2. Aberrant markings (15%) were
      mostly related to software problems. No differences were found regarding age,
      gender, cognitive/physical performance, or previous computer experience. Study 3:
      70% of the patients had identical markings on the computer and paper maps. Only
      four patients had completely different markings on the two maps. CONCLUSION: This
      first version of CPBM was well accepted by patients with advanced cancer.
      However, several areas for improvement were revealed, providing a basis for the
      development of the next version, which is subject to further international
      testing.

PMID- 23856100
TI  - Olanzapine for the prevention of chemotherapy-induced nausea and vomiting in
      patients receiving highly or moderately emetogenic chemotherapy: a randomized,
      double-blind, placebo-controlled study.
AB  - CONTEXT: Chemotherapy-induced nausea and vomiting (CINV) can severely impair
      patients' quality of life (QOL). Psychotropics, especially olanzapine, have a
      strong antiemetic effect. OBJECTIVES: To determine whether olanzapine could
      reduce the frequency of CINV and improve patients' QOL during chemotherapy.
      METHODS: This was a randomized, double-blind, placebo-controlled trial. Forty
      four patients scheduled to receive highly or moderately emetogenic chemotherapy
      were enrolled. All patients received a 5-hydroxytryptamine3 receptor antagonist,
      steroid, and neurokinin-1 receptor antagonist. Patients were randomly assigned to
      take 5 mg/day of oral olanzapine (OL group, n = 22) or placebo (control group, n
      = 22) daily from the day before chemotherapy (Day 0) to Day 5. The primary
      endpoint was the rate of patients who achieved total control (no vomiting, no use
      of rescue medications, and maximum nausea of <5/100mm on a visual analogue
      scale). The secondary endpoint was Functional Living Index-Emesis questionnaire
      score on Days 0 and 6. RESULTS: The rate of patients achieving total control was
      significantly higher in the OL group (86% and 64% in acute and delayed phases,
      respectively) than in the control group (55% and 23%, P = 0.045, P = 0.014,
      respectively). Furthermore, the OL group experienced a better QOL than the
      control group, as reported on the Functional Living Index-Emesis questionnaire (P
      = 0.0004). CONCLUSION: The addition of 5mg/day of oral olanzapine to standard
      therapy can reduce the frequency of CINV and improve QOL of patients receiving
      highly or moderately emetogenic chemotherapy.

PMID- 23856099
TI  - Self-reported physical symptoms in intensive care unit (ICU) survivors: pilot
      exploration over four months post-ICU discharge.
AB  - CONTEXT: Survivors of critical illness must overcome persistent physical and
      psychological challenges. Few studies have longitudinally examined self-reported
      physical symptoms in intensive care unit (ICU) survivors. OBJECTIVES: To describe
      prevalence and severity of self-reported symptoms in 28 adult medical ICU
      survivors during the first four months post-ICU discharge and their associations
      with family caregiver responses. METHODS: Patients completed the Modified Given
      Symptom Assessment Scale. Caregivers completed the Shortened 10-item Center for
      Epidemiologic Studies Depression Scale, Brief Zarit Burden Score, Pittsburgh
      Sleep Quality Index, and the Caregiver Health Behavior form. Data at ICU
      discharge (two weeks or less), and two and four months post-ICU discharge were
      analyzed. RESULTS: Across the time points, most patients reported one or more
      symptoms (88.5-97%), with sleep disturbance, fatigue, weakness, and pain the most
      prevalent. For these four symptoms with the highest prevalence, there were: 1)
      moderate correlations among symptom severity at two and four months post-ICU
      discharge; and 2) no difference in prevalence or severity by patients'
      disposition (home vs. institution), except worse fatigue in patients at home at
      two weeks or less post-ICU discharge. Patients' overall symptom burden showed
      significant correlation with caregivers' depressive symptoms two weeks or less
      post-ICU discharge. There were trends of moderate correlations between patients'
      overall symptom burden and caregivers' health risk behaviors and sleep quality at
      two and four months post-ICU discharge. CONCLUSION: In our sample, sleep
      disturbance, fatigue, weakness, and pain were the four key symptoms during first
      four months post-ICU discharge. Future studies focusing on these four symptoms
      are necessary to promote quality in post-ICU symptom management.

PMID- 23856101
TI  - Synthetic peptides for in vitro evaluation of the neutralizing potency of
      Loxosceles antivenoms.
AB  - An important step in the development of therapeutic antivenoms is the pre
      clinical testing using in vivo methods to assess their neutralizing potency. For
      spider antivenoms (Loxosceles species), horse serum potency against the
      necrotizing activities of Loxosceles intermedia crude venom is currently tested
      in rabbits. These procedures are time consuming and involve a large number of
      animals. The aim of this study was to develop an in vitro method to assess the
      neutralizing potency of anti-Loxosceles sera. We first demonstrated that it was
      not possible to establish a correlation between the ELISA antibody reactivity of
      horse anti-Loxosceles serum and their neutralizing potency. We then showed that
      the antivenoms recognized several peptide epitopes from different regions of
      SMase-D proteins, which are toxic antigens from Loxosceles venoms. The
      recognition of some peptides was observed only when high neutralizing potency
      sera was used. Based on these results, three peptides (peptide 1, DNRRPIWNLAHMVNA
      and peptide 3, DFSGPYLPSLPTLDA corresponding to residues 2-16 and 164-178,
      respectively, of SMase-1 protein from Loxosceles laeta, and peptide 2,
      EFVNLGANSIETDVS corresponding to residues 22-36 of A1H - LoxGa protein from
      Loxosceles gaucho and LiD1 protein from L. intermedia) were selected. The
      peptides were synthesized, coupled to bovine serum albumin (BSA), and used as
      antigens in indirect ELISA to test their reactivity with horse anti-Loxosceles
      serum of varying neutralizing potencies. We found certain assay conditions that
      discriminated between the high and low neutralizing potency sera. This study
      introduced an in vitro and peptide-based neutralization assay for anti-Loxosceles
      antivenoms. 

PMID- 23856103
TI  - [Pay attention to enhance the hypertension control].

PMID- 23856102
TI  - "Real world" treatment of metastatic renal cell carcinoma in a joint community
      academic cohort: progression-free survival over three lines of therapy.
AB  - BACKGROUND: New targeted therapeutics approved for metastatic renal cell
      carcinoma (mRCC) offer multiple options in each line of therapy; however, there
      are few prospective data beyond the first-line settings, and overall comparative
      effectiveness data are limited. In the targeted therapy era, progression-free
      survival (PFS) has been the most common regulatory end point for demonstrating
      the benefit of new therapies. PATIENTS AND METHODS: Drawing on a joint community
      academic retrospective mRCC registry, we analyzed all patients who had undergone
      at least 1 line of systemic therapy (N = 325) for PFS. Patients were grouped
      according to treatment choice (sorafenib, sunitinib, temsirolimus, everolimus,
      and "other") for up to 3 lines of therapy. PFS by treatment choice and line of
      therapy was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS:
      PFS was longest in patients treated with sunitinib in the first and second lines
      of therapy. First-line PFS for sorafenib, sunitinib, temsirolimus, everolimus,
      and "other" was 6.9, 8.9, 4.2, not analyzed (too few patients), and 10.8 months,
      respectively. Second-line PFS was 4.6, 7.0, 3.2, 3.8, and 4.1 months,
      respectively. Third-line PFS was 4.5, 4.6, 9.9, 4.2, and 2.9, months,
      respectively. The risk of progression in patients treated with temsirolimus was
      about twice that of patients treated with sunitinib in the first and second lines
      of therapy. CONCLUSION: Patients treated with sunitinib had the longest PFS in
      the first and second lines of therapy. PFS from practice-based data appear
      consistent with trial-based expectations; however, practice variation was still
      evident.

PMID- 23856104
TI  - [The prevention and control of cerebrovascular disease: the key strategy to
      prolong the life expectancy in China].

PMID- 23856105
TI  - [A correlation study between body mass index and exercise capacity in patients
      with chronic systolic heart failure].
AB  - OBJECTIVE: To investigate the association between body mass index (BMI) and
      exercise capacity in patients with chronic systolic heart failure. METHODS: The
      elderly patients with chronic systolic heart failure were consecutively recruited
      from 2008 to 2011 in cardiovascular clinic of Zhejiang Hospital. All the
      participants underwent height and weight measurements and BMI was calculated with
      these two parameters. Cardiopulmonary exercise test were performed to achieve
      peak oxygen uptake (PVO(2)), oxygen uptake to body mass ratio (PKVO(2)), oxygen
      uptake to heart ratio (VO(2)/HR) and ventilation/carbon dioxide production
      (VO(2)/VCO(2)). RESULTS: A total of the 273 patients with chronic systolic heart
      failure included 6 underweight patients (BMI < 18.5 kg/m(2)), 113 normal weight
      patients (BMI 18.5 - < 24.0 kg/m(2)), 116 overweight patients (BMI 24.0 - < 28.0
      kg/m(2)), and 38 obese patients (BMI >= 28 kg/m(2)). In both NYHA II and III/IV
      patients, unadjusted correlation analyses showed that BMI was positively related
      to PVO(2) and VO(2)/HR, and was inversely related to PKVO(2) and VE/VCO(2) (P <
      0.05), respectively. Multiple stepwise regression analyses showed age, sex, BMI
      (P < 0.05) and left ventricular ejection fraction (LVEF) were independent
      determinants of PKVO(2), and age and BMI (P < 0.05) were independent determinants
      of VE/VCO(2). CONCLUSIONS: BMI is significantly associated with exercise capacity
      in patients with chronic systolic heart failure, and also independent determinant
      for the PKVO(2) and VE/VCO(2), respectively.

PMID- 23856106
TI  - [The prevalence, awareness, and control of hypertension in Xianghe county of
      Hebei province].
AB  - OBJECTIVE: To investigate the prevalence, awareness, control status and
      associated risk factors of hypertension in a rural population in Xianghe county
      in North China. METHODS: A total of 830 adults (aged >= 35) from Xianghe county
      were examined during July to August, 2011. Blood pressure was obtained using a
      standardized sphygmomanometer after a 5-minute sitting rest. Information on
      gender, age, education level, marital status, smoking, drinking, income, family
      history of hypertension and use of antihypertensive medications was obtained.
      RESULTS: A total of 42.4% of all subjects had hypertension. Among those with
      hypertension, the awareness rate was 54.8% and 50.0% of the patients were taking
      antihypertensive medication with the control rate of 11.9% [BP < 140/90 mm Hg (1
      mm Hg = 0.133 kPa)]. Lower age and education level, lower body mass index,
      negative family history of hypertension were associated with poor awareness of
      hypertension and worse compliance with the treatment. Older age, positive family
      history and alcohol consumption were associated with poor blood pressure control.
      CONCLUSIONS: Hypertension is highly prevalent in Xianghe rural area. The
      awareness, treatment and control rate are all low. There is an urgent need for
      comprehensive strategies to improve prevention, screening, and treatment of
      hypertension in rural China.

PMID- 23856107
TI  - [An evaluation of the impact of cerebrovascular disease deaths on life expectancy
      in China].
AB  - OBJECTIVE: To evaluate the impact of cerebrovascular death on the life expectancy
      of Chinese residents in recent years and explore the difference in the subgroups.
      METHODS: Life expectancy and cause-elimination life expectancy were calculated by
      standard life table techniques using the adjusted mortality data from the Death
      Surveillance Data Sets in 2005 and 2010 provided by the National Disease
      Surveillance System. Decomposition method was used to quantitatively evaluate the
      impact of cerebrovascular disease. RESULTS: The life expectancy of Chinese
      residents was 73.23 years old in 2010. The loss of life expectancy caused by
      cerebrovascular death was 2.26 years in 2010, with about 97% of that came from
      the elimination of deaths in the residents aged over 40 years old. Compared with
      2005, the reduction of cerebrovascular deaths contributed to a total of 0.04
      years increase in the life expectancy of Chinese residents in 2010, with 0.45
      years for urban residents. However, for the rural residents, cerebrovascular
      death increased and caused 0.12 years decrease of life expectancy. CONCLUSIONS:
      The impact of cerebrovascular death on the life expectancy of Chinese residents
      is still great. Significant difference is showed between the urban and rural
      areas with reduction in the urban but increase in the rural. The life expectancy
      is likely to be further increased by reducing cerebrovascular death in the
      Chinese residents aged over 40 years old.

PMID- 23856108
TI  - [Hennekam syndrome: a case report and review of literature].
AB  - OBJECTIVE: To study the clinical characteristics of Hennekam syndrome. METHODS:
      We described a case of long-term iron deficiency anemia, characteristic facial
      anomalies, growth retardation, and intestinal lymphangiectasia. To our knowledge,
      this is the first case of Hennekam syndrome reported in China. Meanwhile,
      relevant literature was also reviewed. RESULTS: A total of 35 cases of Hennekam
      syndrome were identified, consisting of 18 males and 17 females (age ranging 0 -
      40 years old). Lymphangiectasia, lymphedema, facial anomalies (hypertelorism,
      flat nasal bridge and flat face) and developmental retardation were the major
      clinical manifestations of the syndrome. CCBE1 mutation may have played an
      important role in the pathogenesis of the syndrome. Long-term moderate-to-severe
      iron deficiency anemia was a distinctive feature of our case. Lymphangiography
      revealed lymphangiectasia of small intestine and lower limb, as well as thoracic
      outlet obstruction. Complete elimination of anemia and significant increase of
      serum albumin level were observed several months after the adhesiolysis procedure
      of the distal end of thoracic duct. However, anemia and severe hypoalbuminemia
      relapsed after taking greasy food. CONCLUSIONS: Hennekam syndrome is a rare
      autosomal recessive syndrome characterized by defective lymphatic development.
      Congenital lymphangiectasia should be considered in the patients with unexplained
      developmental retardation and hypoalbuminemia. Moreover, intestinal
      lymphangiectasia can be a rare cause of gastrointestinal bleeding.

PMID- 23856109
TI  - [Cardiac involvement of the type I mucopolysaccharidosis].
AB  - OBJECTIVE: To investigate the manifestations of cardiac involvement in the
      patients with mucopolysaccharidosis I (MPS I). METHODS: The clinical data of 10
      MPS I patients were collected. Electrocardiography (ECG) and echocardiography
      (Echo) were performed in all patients and then analyzed. RESULTS: Among the ten
      patients, seven were men. The onset age of MPS was (0.5 ~ 8.0) years old and the
      age of diagnosis was (1.8 ~ 20.0) years old. Two patients had grade 2 precordial
      systolic murmur. ECG was abnormal in three patients with right ventricular
      hypertrophy in two and right axis deviation in another one. Echo showed valvular
      thickening and insufficiency in nine patients, enlarged left atrium and ventricle
      in one patient, pulmonary hypertension and right ventricular hypertrophy in two
      patients and abnormal left ventricular configuration in five patients.
      CONCLUSIONS: Cardiac involvement is common in MPS I patients and may present as
      valvular thickening with regurgitation, abnormal left ventricular configuration
      and pulmonary hypertension. The cardiac involvement progresses with age. ECG and
      Echo should be done regularly during follow-up of MPS I patients.

PMID- 23856110
TI  - [Observations on fatigue, depression and quality of life in patients with
      Parkinson's disease].
AB  - OBJECTIVE: To identify the association between fatigue and depression in
      Parkinson's disease (PD). METHODS: 56 PD patients were enrolled in this study.
      The degree of fatigue was measured by Fatigue Severity Scale (FSS). Hamilton
      Depression Scale (24 items) was used to evaluate the degree of depression. PD
      Quality of Life Questionnaire (PDQL) were tested to evaluate the quality of life
      in PD patients. While other clinical information such as Unified Parkinson's
      Disease Rating Scale (UPDRS) III, Hoehn-Yahr Scale and modified Webster Scale
      were investigated. RESULTS: The incidence of fatigue in this group is 71.4%
      (40/56). Score of HAMD and PDQL exhibited a significant correlation to patients'
      fatigue, coefficient of partial correlation was 0.451 (P < 0.01), -0.346 (P <
      0.05). The incidence of fatigue in non-depressive patients was low, 27.3%. While
      in depressive patients, the incidence of fatigue is relatively high, for mild
      depression 75%, moderate depression 100%, severe depression 100% respectively.
      CONCLUSIONS: Fatigue is a prominent symptom of depression in PD patients,
      sometimes independent of depression also influencing the patients' quality of
      life.

PMID- 23856111
TI  - [An analysis of resistance of nosocomial infection pathogens isolated from 13
      teaching hospitals in 2011].
AB  - OBJECTIVE: To investigate the pathogen profile of nosocomial infection in China,
      and to survey the susceptibility rates of these pathogens to the clinical common
      antibiotics. METHODS: The non-repetitive nosocomial pathogens isolated from
      bloodstream infection (BSI), hospital acquired pneumonia (HAP) and intra
      abdominal infection (IAI) and the case data were collected from 13 teaching
      hospitals in different areas of China and sent to a central laboratory for re
      identification and susceptibility testing. The levels of minimal inhibitory
      concentration (MIC) of the common antibiotics were determined by agar dilution
      method. The data were analyzed by WHONET 5.6 software. RESULTS: A total of 2103
      clinical isolates were collected from January to December 2011, of which gram
      positive cocci and gram negative organisms accounted for 23.2% and 76.8%
      respectively. The top three pathogens of BSI were E. coli (31.0%, 243/784), K.
      pneumoniae (14.8%, 116/784) and S. aureus (10.6%, 83/784). The top three
      pathogens of HAP were A. baumannii (24.2%, 158/652), P. aeruginosa (23.0%,
      150/652) and K. pneumoniae (16.4%, 107/652). The top three pathogens of IAI were
      E. coli (34.3%, 229/667), E. faecium (13.3%, 89/667) and K. pneumoniae (9.6%,
      64/667). Methicillin-resistant S. aureus (MRSA) and coagulase negative
      Staphylococcus (MRCNS) accounted for 64.4% and 78.1% respectively. The
      susceptibility rates of Staphylococcus species to tigecycline, vancomycin,
      teicoplanin and linezolid were all 100%. The prevalence of MRSA in HAP was
      significantly higher than that in BSI or IAI. The susceptibility rates of
      Enterococcus species to tigecycline, teicoplanin and linezolid were all 100%. The
      prevalence of extended-spectrum beta-lactamases (ESBL) was 64.3% in E. coli and
      38.3% in K. pneumonia. Against Enterobacteriaceae, the most active agents were as
      following in order: tigecycline (92.3% - 100%) [except P.mirabilis], meropenem
      (87.5% - 100%), imipenem (87.5% - 100%) [except M. morganii], amikacin (87.5% -
      100%), polymyxin B (75% - 100%) [except S. marcescens, P. mirabilis and M
      morganii], cefepime (67.8% - 100%), cefoperazone-sulbactam (66.6% - 100%),
      piperacillin-tazobactam (61.5% - 100%). Carbapenem-resistance Enterobacteriaceae
      strains emerged. The susceptibility rates of P. aeruginosa to imipenem and
      meropenem were 66.2% and 72.2%, respectively. The susceptibility rates of A.
      baumannii to imipenem and meropenem were 27.7% and 25.9%, respectively. The most
      active agents against A. baumannii were polymyxin B (100%), followed by
      tigecycline (79.8%) and minocycline (50.4%). The susceptibility rates of
      P.aeruginosa to antibiotics in BSI were higher than those in HAP and IAI.
      Susceptibility rates of S. maltophilia to trimethoprim-sulfamethoxazole,
      minocycline and levofloxacin were about 90% or above. Susceptibility rates of B.
      cepacia to trimethoprim-sulfamethoxazole, ceftazidime and meropenem were all
      100%. Several P.aeruginosa and A. baumannii strains were resistant to all tested
      antibiotics except polymyxin B. CONCLUSIONS: The pathogen profile is different in
      different types of infection. The prevalence of multi-drug resistant A. baumannii
      is high, which is still a key problem of nosocomial infection. Tigecycline
      remains relatively high activity against gram-positive cocci and gram-negative
      bacteria (except P. aeruginosa and P. mirabilis) in vitro.

PMID- 23856112
TI  - [Myelopathy associated with systemic lupus erythematosus: a clinical analysis of
      10 cases and review of literature].
AB  - OBJECTIVE: To analyze the clinical features, therapy and outcome of systemic
      lupus erythematosus (SLE) combined with lupus myelopathy (LM). METHODS: Ten SLE
      patients combined with LM treated in Department of Rheumatology and Immunology,
      People's Hospital from 1990 to 2011 were retrospectively analyzed and 43 cases of
      SLE combined with LM reported home and abroad were reviewed. RESULTS: All the ten
      patients were women with age of 23 - 53 (36.9 +/- 3.4) years old and duration of
      1 - 18 years. MRI of spinal cord revealed long T2 signal in one case, and normal
      in two cases. Seven patients received methylprednisolone pulse plus
      cyclophosphamide (CTX), two were given glucocorticoid pulse only, and one was
      given moderate dosage of glucocorticoid, CTX and plasma exchange (PE). The
      results revealed that four patients received complete recovery, four received
      partial recovery, and two received no improvement. CONCLUSIONS: LM is a rare but
      severe complication of SLE with poor prognosis, which usually occurs in early
      phase of young SLE patients. Pulse methylprednisolone and CTX may be effective.
      Early and active treatment may improve the outcome.

PMID- 23856113
TI  - [The clinical study of invasive fungal infection in 76 cases of hematologic
      diseases].
AB  - OBJECTIVE: To investigate the risk factors, clinical features, efficacy and
      adverse reactions in patients of hematologic diseases with invasive fungal
      infections (IFI). METHODS: The risk factors and clinical features were
      retrospectively analyzed to compare the efficacy and safety of itraconazole with
      amphotericin B in treatment of IFI in 76 patients with hematologic diseases.
      RESULTS: Of the 76 patients, 68 (89.5%) used broad-spectrum antibiotics, 64
      (84.2%) were treated with more than 2 courses chemotherapy, 43 (56.6%) were under
      agranulocytosis, 34 (44.7%) were using glucocorticoid for long terms, 27 (35.5%)
      were with peripheral or central venous catheter. The overall effective rates of
      itraconazole and amphotericin B were 60.5% and 61.5% respectively (P = 0.929).
      There was a significant difference between itraconazole and amphotericin B in
      hypokalemia (14.0% vs 42.4%, P = 0.005) while no other differences in adverse
      reactions were found. CONCLUSIONS: The risk factors of patients in hematologic
      diseases with IFI include chemotherapy, using broad septum antibiotics and
      agranulocysis. The therapeutic effect of itraconazole and amphotericin B in
      treatment of IFI is similar. The adverse reactions of itraconazole is less and
      slighter than amphotericin B.

PMID- 23856114
TI  - [The value of the current diagnostic criteria of pulmonary invasive fungal
      infection after allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To analyze the practicality of current diagnostic criteria of invasive
      fungal infection (IFI) in patients with hematologic diseases/malignant tumors, so
      as to enhance the recognition of characteristics of pulmonary IFI after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The
      clinical features of 51 cases with IFI after allo-HSCT were analyzed
      retrospectively. RESULTS: Pulmonary IFI accounted for 42.1% (51/121) of the whole
      infectious pneumonia diagnosed among the patients admitted during the study. One
      (2.0%) case was proven diagnosis; 24 (47.1%) were probable diagnosis and 26
      (51.0%) were possible diagnosis. The using of immuno-suppressors and
      corticosteroids, and the presence of graft-versus-host disease (GVHD) were the
      main host factors. The patients with two or more host factors simultaneously
      accounted for 66.7% (34/51) of all pulmonary IFI patients. Totally 94.1% (48/51)
      of the patients with pulmonary IFI presented nodules and/or patches as the main
      features in high resolution computed tomography (HRCT) scanning. The positive
      rates of fungal antigen detection were 58.6% for G test and 33.3% for GM test,
      which were relatively high. Twenty patients (39.2%) showed decrease of arterial
      partial pressure of oxygen and hypoxia in blood-gas analysis. CONCLUSIONS: For
      the diagnosis of pulmonary IFI post allo-HSCT, the administration of immuno
      suppressors and corticosteroids, and the presence of GVHD were the main host
      factors. Nodules and/or patches were the main features in HRCT image. Fungus
      antigen detection is the main tool to support clinical diagnosis.

PMID- 23856115
TI  - Co-operative inhibitory effects of hydrogen peroxide and iodine against bacterial
      and yeast species.
AB  - BACKGROUND: Hydrogen peroxide and iodine are powerful antimicrobials widely used
      as antiseptics and disinfectants. Their antimicrobial properties are known to be
      enhanced by combining them with other compounds. We studied co-operative
      inhibitory activities (synergism, additive effects and modes of growth
      inhibition) of hydrogen peroxide and iodine used concurrently against 3 bacterial
      and 16 yeast species. RESULTS: Synergistic or additive inhibitory effects were
      shown for hydrogen peroxide and iodine mixtures against all 19 species used in
      the study. Both biocides were mostly cidal individually and in mixtures against
      Pseudomonas aeruginosa and Staphylococcus aureus. Both compounds manifested
      static inhibitory effects individually, but their mixtures were synergistically
      cidal for Saccharomyces cerevisiae and Escherihia coli. Cells of S. cerevisiae
      treated with hydrogen peroxide and iodine-hydrogen peroxide mixture produced
      increased numbers of respiratory deficient mutants indicating genotoxic effects.
      CONCLUSION: Iodine and hydrogen peroxide used concurrently interact
      synergistically or additively against a range of prokaryotic and eukaryotic
      microorganisms. The study provides an insight as to how these traditional
      antimicrobials could be used more effectively for disinfection and antisepsis. In
      addition, a simple approach is proposed for scoring genotoxicity of different
      biocides by using the budding yeast system.

PMID- 23856116
TI  - Socio-technical systems and interaction design - 21st century relevance.
AB  - This paper focuses on the relationship between the socio-technical system and the
      user-technology interface. It looks at specific aspects of the organisational
      context such as multiple user roles, job change, work processes and workflows,
      technical infrastructure, and the challenges they present for the interaction
      designer. The implications of trends such as more mobile and flexible working,
      the use of social media, and the growth of the virtual organisation, are also
      considered. The paper also reviews rapidly evolving technologies such as
      pervasive systems and artificial intelligence, and the skills that workers will
      need to engage with them. 

PMID- 23856117
TI  - Characterization of FlipIDAM as a SERT-selective SPECT imaging agent.
AB  - INTRODUCTION: Biological evaluation of ([(125)I]4), a new single-photon emission
      computed tomography (SPECT) radioligand for imaging the serotonin transporter
      (SERT) which displayed improved in vivo kinetics for mapping SERT binding sites
      in the brain. METHODS: In vitro binding studies of [(125)I]4 were performed with
      membrane homogenates of LLC-PK1 cells stably transfected and overexpressing one
      of the monoamine transporter (SERT, DAT or NET) and rat cortical homogenates.
      Biodistribution and ex vivo autoradiography studies were carried out in rats. In
      vivo competition experiments were evaluated to determine the SERT selectivity of
      [(125)I]4 vs. ([(125)I]1). RESULTS: In vitro binding studies of 4 showed
      excellent binding affinity (Ki,SERT=0.90 +/- 0.05 nM) and excellent selectivity
      over the other monoamine transporters (100 fold and >4000 fold for NET and DAT
      respectively). Scatchard analysis of saturation binding of [(125)I]4 to rat
      cortical homogenates gave a Kd value of 0.5 +/- 0.09 nM and a Bmax value of 801.4
      +/- 58.08 fmol/mg protein. The biodistribution study showed rapid high brain
      uptake (3.09 +/- 0.11% dose/organ at 2 min) and a good target to non-target ratio
      (hypothalamus to cerebellum) at 30 min (2.62) compared to [(125)I]1 (2.19). Ex
      vivo autoradiography showed that FlipIDAM localizes in accordance with SERT
      distribution patterns in the brain. In vivo and ex vivo competition experiments
      with specific and non-specific SERT compounds also showed that [(125)I]4 binds
      specifically to SERT rich regions. CONCLUSIONS: The biological evaluation of
      [(125)I]4 demonstrates that [(123)I]4 would be a good candidate for SPECT imaging
      of SERT.

PMID- 23856118
TI  - Mobility and distribution of arsenic in contaminated mine soils and its effects
      on the microbial pool.
AB  - Three soils, coming from a former mining site and characterized by a different
      degree of pollution, were analysed in terms of Arsenic (As) content, using three
      different analytical approaches, and its distribution in various soil fractions.
      The effect of As on soil microbial biomass (size, respiration and microbial
      quotients) was also analysed. Total arsenic concentration between soil fractions
      was significantly different and ranged from 189 to 4357mgkg(-1), indicating a
      high level of pollution. Soil sequential fractioning showed that more than 60
      percent of total As was bound to Fe-Al oxides, suggesting a minor availability
      and environmental risk regardless the total concentration of As in the sample. On
      the contrary, water soluble As fraction showed a significant difference among the
      three samples. The largest water soluble As concentration was found in the sample
      with intermediate total As amount. As far as microbial biomass is concerned, it
      was found that bioavailable As negatively impacted microbial metabolism in terms
      of basal and cumulative respiration, and microbial quotients, suggesting a strong
      selection within microbial pool. 

PMID- 23856119
TI  - Derivation of South African water quality guidelines for Roundup((r)) using
      species sensitivity distribution.
AB  - Glyphosate-based herbicides are among the leading products used in South Africa
      to control weeds and invading alien plant species. Although these herbicides
      ultimately find their way into aquatic ecosystems, South Africa has no water
      quality guideline based on indigenous species to protect the country's aquatic
      biota against these biocides. In this study, South African water quality
      guidelines (SAWQGs) for Roundup((r)) based on species sensitivity distribution
      (SSD) using indigenous aquatic biota were developed. Short-term and long-term
      toxicity tests were conducted with eight different aquatic species belonging to
      five different taxonomic groups. Static non-renewal experimental methods were
      employed for short-term lethal tests (<=4 days), and static renewal for long-term
      sublethal tests (>=4 days <=21 days). LC50 values for animal exposure and EC50
      values for algae were calculated using probit analysis and linear regression of
      transformed herbicide concentration as natural logarithm data against percentage
      growth inhibition, respectively. No effect concentration (NEC) was determined
      based on the dynamic energy budget model, using survival data. The LC50, EC50 and
      NEC values were used to develop species sensitivity distribution (SSD)
      concentrations for Roundup((r)). Based on the SSD concentrations, the short-term
      and long-term SAWQGs for Roundup((r)) were derived as 0.250 (0.106-0.589) mg/L,
      and 0.002 (0.000-0.021) mg/L, respectively. These WQGs may be useful in
      protecting South African aquatic life against transient or long-term exposure to
      glyphosate-based chemicals as part of integrated water resources management. 

PMID- 23856120
TI  - Isolation and characterization of a novel 2-methyl-4-chlorophenoxyacetic acid
      degrading Enterobacter sp. strain SE08.
AB  - A bacterial strain (SE08) capable of utilizing 2-methyl-4-chlorophenoxy acetic
      acid (MCPA) as the sole carbon and energy source for growth was isolated by
      continuous enrichment culturing in minimal salt medium (MSM) from a long term
      MCPA exposed soil. This bacterial strain was identified as Enterobacter sp. based
      on morphological, physiological and biochemical tests, as well as 16S rRNA
      sequence analysis. Its ability to degrade MCPA was determined using high
      performance liquid chromatography. The strain SE08 can tolerate unusually high
      MCPA concentrations (125-2000mg/L). The influences of culturing factors (initial
      concentration, pH, and temperature) on the bacterial growth and substrate
      degradation were studied. The results showed that the optimal MCPA degradation
      occurred at an MCPA concentration of 500mg/L, 30 degrees C and pH 6.0. Under
      these conditions, 68.5 percent of MCPA in MSM was degraded by SE08, and the
      OD600nm reached 0.64 after culturing for 72h. The degradation of MCPA could be
      enhanced by addition of both carbon and nitrogen sources. At an initial MCPA
      concentration of 500mg/L, when 5g/L glucose and 2.5g/L yeast extract were added
      into the MSM media, the MCPA degradation was significantly increased to 83.8
      percent, and OD600nm was increased to 1.09 after incubation at 30 degrees C and
      pH 6.0 for 72h. This is the first study showing that an Enterobacter sp. strain
      is capable of degrading MCPA, which might provide a new approach for the
      remediation of MCPA contaminated soil and contribute to the limited knowledge
      about the function of Enterobacter species. 

PMID- 23856121
TI  - The effect of alum coagulation for in-lake treatment of toxic Microcystis and
      other cyanobacteria related organisms in microcosm experiments.
AB  - Microcosm and bottle experiments were conducted to evaluate the effects of alum
      treatment on cyanobacteria-lysing organisms and microcystin-degrading bacteria as
      well as Microcystis cells, and to provide detailed evidence of Microcystis cell
      damage by investigating precipitated Microcystis cells. The alum concentration to
      be pH 6.0 is the maximum which does not cause toxicity by monomeric Al,
      therefore, this concentration was defined as maximum dose. Microcystis cells were
      considerably damaged by the alum treatment with maximum dose and long contact
      time. Seven days post-treatment, intracellular microcystin-LR was released into
      the extracellular environment in excess of 95 percent and chlorophyll a is not
      easily released from inside the cell, chl.a of precipitated Microcystis cells was
      also decreased to approximately 50 percent. Moreover, alum treatment caused
      damage to cyanobacteria-lysing organisms and microcystin-degrading bacteria, as
      well as to Microcystis cells. Therefore, it could be concluded that alum
      treatment with maximum dose (48 mg L(-1) as AI) is not suitable for removing
      cyanobacterial bloom without the release of cyanotoxin in reservoirs and ponds. 

PMID- 23856122
TI  - The relationship of cytotoxic and genotoxic damage with blood aluminum levels and
      oxidative stress induced by this metal in common carp (Cyprinus carpio)
      erythrocytes.
AB  - Aluminum is one of the most abundant elements in nature and is used in diverse
      industrial processes. As a result, it contaminates aquatic ecosystems, inducing
      damage on associated biota. In fish, it has been observed to induce hypoxia,
      hypercapnia, metabolic acidosis and respiratory arrest. Although there is little
      information on Al-induced cytotoxicity and DNA damage, this type of studies are
      essential in order to identify the mechanisms of action of this metal. The
      cytotoxic and genotoxic effects induced by Al on common carp (Cyprinus carpio)
      erythrocytes were determined in specimens exposed to 0.05, 120 and 239mgAlL(-1)
      in static exposure systems. Blood samples were taken at 12, 24, 48, 72 and 96h,
      erythrocytes were separated, and the following were evaluated: frequency of
      micronuclei and frequency of terminal deoxynucleotidyl transferase dUTP nick-end
      labeling (TUNEL)-positive cells, blood Al levels, lipid peroxidation, protein
      carbonyl content, and activity of the antioxidant enzymes superoxide dismutase,
      catalase and glutathione peroxidase. The results show that tested aluminum
      concentrations produces oxidative stress (increase in lipid peroxidation degree
      and oxidized proteins content, as well as decrease in antioxidant enzymes
      activity) and induced higher frequencies of micronuclei and TUNEL-positive cells,
      so this metal can be considered as a cytotoxic and genotoxic agent for
      erythrocytes of common carp. 

PMID- 23856123
TI  - Response of different populations of seven lady beetle species to lambda
      cyhalothrin with record of resistance.
AB  - Simultaneous use of biological and chemical controls is a valued and historic
      goal of integrated pest management, but has rarely been achieved. One explanation
      for this failure may be the inadequate documentation of field populations of
      natural enemies for insecticide tolerance or resistance because natural enemies
      surviving insecticide application do not create problems like resistant pest
      species. Therefore, this study investigated 31 populations of lady beetles
      (Coleoptera: Coccinellidae) regarding their susceptibility to lambda-cyhalothrin,
      a pyrethroid insecticide that is widely used in cotton and other crops to control
      lepidopteran and coleopteran pests that are not targeted as prey by lady beetles.
      The study focused on seven coccinellid species common in cotton fields
      Coleomegilla maculata De Geer, Cycloneda sanguinea (L.), Eriopis connexa Germar,
      Harmonia axyridis (Pallas), Hippodamia convergens Guerin-Meneville, Olla v-nigrum
      (Mulsant), and Brumoides foudrasi (Mulsant) and one lady beetle species [Curinus
      coeruleus Mulsant] from a non-cotton ecosystem for comparisons. Dose-mortality
      curves were estimated after topical treatment of adult lady beetles with lambda
      cyhalothrin. Statistically significant variations in lady beetle susceptibility
      were observed between species and between populations of a given species. Seven
      and eighteen populations of lady beetles exhibited greater values of LD50 and
      LD90, respectively, than the highest recommended field rate of lambda-cyhalothrin
      (20g a.i./hectare~0.2g a.i./L) for cotton fields in Brazil. Furthermore, based on
      LD50 values, 29 out of 30 tested populations of lady beetles exhibited ratios of
      relative tolerance varying from 2- to 215-fold compared to the toxicity of lambda
      cyhalothrin to the boll weevil, Anthonomus grandis Boh. (Coleoptera:
      Curculionidae). Four populations of E. connexa were 10.5-37.7 times more tolerant
      than the most susceptible population and thus were considered to be resistant to
      lambda-cyhalothrin, the first record of resistance for this species. These
      findings demonstrate that field selection for resistance to lambda-cyhalothrin in
      common lady beetles is occurring, opening up possibilities to effectively
      integrate biological control where the popular insecticide lambda-cyhalothrin is
      used. 

PMID- 23856124
TI  - Grazing on Microcystis aeruginosa and degradation of microcystins by the
      heterotrophic flagellate Diphylleia rotans.
AB  - Cyanobacterial toxins can cause damage in aquatic ecosystems worldwide, as well
      as the poisoning of livestock, plants and humans when ingested in large amounts.
      Although many studies investigated grazing of harmful cyanobacteria by metazoan
      plankton, grazing of cyanobacteria by hetertophic flagellates is largely
      unexplored. This laboratory study investigated grazing of toxic Microcystis
      aeruginosa by the heterotrophic flagellate Diphylleia rotans isolated from a
      Saudi hypertrophic lake. D. rotans was able to feed on M. aeruginosa with
      estimated ingestion (10.2 to 16.5 prey flagellate (-1)d(-1)) and specific growth
      rates (0.71 to 0.99d(-1)) differed with the increase in the initial density of
      the flagellate. Grazing increased microcystin production within Microcystis cells
      during first two days of incubation, and afterwards induced the release of these
      toxins into the medium. The concentrations of releasing microcystin were strongly
      reduced in grazing-treated cultures compared to controls, indicating the
      degradation of microcystins by D. rotans growing under axenic conditions. Taken
      these results, D. rotans can play an important role in the reduction of
      Microcystis biomass and microcystin toxins, and thus could be used as a safe
      bioagent for the biocontrol of harmful algal blooms in aquatic environments. 

PMID- 23856126
TI  - Hypercoagulability in response to elevated body temperature and central
      hypovolemia.
AB  - BACKGROUND: Coagulation abnormalities contribute to poor outcomes in critically
      ill patients. In trauma patients exposed to a hot environment, a systemic
      inflammatory response syndrome, elevated body temperature, and reduced central
      blood volume occur in parallel with changes in hemostasis and endothelial damage.
      The objective of this study was to evaluate whether experimentally elevated body
      temperature and reduced central blood volume (CBV) per se affects hemostasis and
      endothelial activation. METHODS: Eleven healthy volunteers were subjected to heat
      stress, sufficient to elevate core temperature, and progressive reductions in CBV
      by lower body negative pressure (LBNP). Changes in hemostasis were evaluated by
      whole blood haemostatic assays, standard hematologic tests and by plasma
      biomarkers of coagulation and endothelial activation/disruption. RESULTS:
      Elevated body temperature and decreased CBV resulted in coagulation activation
      evidenced by shortened activated partial tromboplastin time (-9% [IQR -7; -4]),
      thrombelastography: reduced reaction time (-15% [-24; -4]) and increased maximum
      amplitude (+4% (2; 6)), all P < 0.05. Increased fibrinolysis was documented by
      elevation of D-dimer (+53% (12; 59), P = 0.016). Plasma adrenaline and
      noradrenaline increased 198% (83; 346) and 234% (174; 363) respectively (P =
      0.006 and P = 0.003). CONCLUSIONS: This experiment revealed emerging
      hypercoagulability in response to elevated body temperature and decreased CBV,
      whereas no effect on the endothelium was observed. We hypothesize that elevated
      body temperature and reduced CBV contributes to hypercoagulability, possibly due
      to moderate sympathetic activation, in critically ill patients and speculate that
      normalization of body temperature and CBV may attenuate this hypercoagulable
      response.

PMID- 23856127
TI  - Effects of rikkunshito, a kampo medicine, on quality of life after proximal
      gastrectomy.
AB  - BACKGROUND: The loss of the gastroesophageal junction after proximal gastrectomy
      (PG) induces various gastrointestinal symptoms, such as regurgitation, anorexia,
      and body weight loss, leading to impairment of the postoperative quality of life.
      In the present study, we investigated the long-term quality of life and the
      effects of rikkunshito, a traditional Japanese medicine (kampo), on the
      gastrointestinal symptoms and plasma ghrelin levels in patients with gastric
      cancer who had undergone PG. METHODS: Nineteen patients who had undergone PG> 6
      mo before entry into the present study were enrolled. The plasma ghrelin levels,
      body weight, appetite, and Gastrointestinal Symptom Rating Scale (GSRS) scores
      were examined before and after the 4-wk administration of rikkunshito. A subgroup
      analysis was performed of patients showing a GSRS score of >= 2 before treatment,
      indicating the presence of gastrointestinal symptoms. RESULTS: The patients' body
      weight increased significantly after the administration of rikkunshito. Neither
      their appetite nor plasma acylated and deacylated ghrelin levels were
      significantly affected. In the subgroup analysis, the mean total GSRS score
      improved significantly from 2.6 +/- 0.6 before the administration of rikkunshito
      to 1.9 +/- 0.7 after administration because of the significant improvement in the
      subscale scores for abdominal pain, acid reflux, diarrhea, and constipation.
      CONCLUSIONS: The long-term quality of life was well preserved in the patients who
      had undergone PG at our hospital. In the patients with a baseline GSRS score of
      >=2, rikkunshito significantly improved the symptoms of postgastrectomy syndrome,
      and its effect was possibly independent of the plasma ghrelin levels.

PMID- 23856125
TI  - Molecular mechanisms of thoracic aortic dissection.
AB  - Thoracic aortic dissection (TAD) is a highly lethal vascular disease. In many
      patients with TAD, the aorta progressively dilates and ultimately ruptures.
      Dissection formation, progression, and rupture cannot be reliably prevented
      pharmacologically because the molecular mechanisms of aortic wall degeneration
      are poorly understood. The key histopathologic feature of TAD is medial
      degeneration, a process characterized by smooth muscle cell depletion and
      extracellular matrix degradation. These structural changes have a profound impact
      on the functional properties of the aortic wall and can result from excessive
      protease-mediated destruction of the extracellular matrix, altered signaling
      pathways, and altered gene expression. Review of the literature reveals
      differences in the processes that lead to ascending versus descending and
      sporadic versus hereditary TAD. These differences add to the complexity of this
      disease. Although tremendous progress has been made in diagnosing and treating
      TAD, a better understanding of the molecular, cellular, and genetic mechanisms
      that cause this disease is necessary to developing more effective preventative
      and therapeutic treatment strategies. 

PMID- 23856128
TI  - Identification of the cell targets important for propolis-induced cell death in
      Candida albicans.
AB  - Candida albicans is the most common fungal pathogen of humans, forming both
      commensal and opportunistic pathogenic interactions, causing a variety of skin
      and soft tissue infections in healthy people. In immunocompromised patients C.
      albicans can result in invasive, systemic infections that are associated with a
      high incidence of mortality. Propolis is a complex mixture of several resinous
      substances which are collected from plants by bees. Here, we demonstrated the
      fungicidal activity of propolis against all three morphogenetic types of C.
      albicans and that propolis-induced cell death was mediated via metacaspase and
      Ras signaling. To identify genes that were involved in propolis tolerance, we
      screened ~800 C. albicans homozygous deletion mutants for decreased tolerance to
      propolis. Fifty-one mutant strains were identified as being hypersensitive to
      propolis including seventeen genes involved in cell adhesion, biofilm formation,
      filamentous growth, phenotypic switching and pathogenesis (HST7, GIN4, VPS34,
      HOG1, ISW2, SUV3, MDS3, HDA2, KAR3, YHB1, NUP85, CDC10, MNN9, ACE2, FKH2, and
      SNF5). We validated these results by showing that propolis inhibited the
      transition from yeast-like to hyphal growth. Propolis was shown to contain
      compounds that conferred fluorescent properties to C. albicans cells. Moreover,
      we have shown that a topical pharmaceutical preparation, based upon propolis, was
      able to control C. albicans infections in a mouse model for vulvovaginal
      candidiasis. Our results strongly indicate that propolis could be used as a
      strategy for controlling candidiasis.

PMID- 23856129
TI  - Temporal dynamics of interference in Simon and Eriksen tasks considered within
      the context of a dual-process model.
AB  - Behavioral and brain potential measures were employed to compare interference in
      Eriksen and Simon tasks. Assuming a dual-process model of interference elicited
      in speeded response tasks, we hypothesized that only lateralized stimuli in the
      Simon task induce fast S-R priming via direct unconditional processes, while
      Eriksen interference effects are induced later via indirect conditional
      processes. Delays to responses for incongruent trials were indeed larger in the
      Eriksen than in the Simon task. Only lateralized stimuli in the Simon task
      elicited early S-R priming, maximal at parietal areas. Incongruent flankers in
      the Eriksen task elicited interference later, visible as a lateralized N2.
      Eriksen interference also elicited an additional component (N350), which
      accounted for the larger behavioral interference effects in the Eriksen task. The
      findings suggest that interference and its resolution involve different processes
      for Simon and Eriksen tasks. 

PMID- 23856130
TI  - Close association between paralogous multiple isomiRs and paralogous/orthologues
      miRNA sequences implicates dominant sequence selection across various animal
      species.
AB  - MicroRNAs (miRNAs) are crucial negative regulators of gene expression at the post
      transcriptional level. Next-generation sequencing technologies have identified a
      series of miRNA variants (named isomiRs). In this study, paralogous isomiR
      assemblies (from the miRNA locus) were systematically analyzed based on data
      acquired from deep sequencing data sets. Evolutionary analysis of paralogous
      (members in miRNA gene family in a specific species) and orthologues (across
      different animal species) miRNAs was also performed. The sequence diversity of
      paralogous isomiRs was found to be similar to the diversity of paralogous and
      orthologues miRNAs. Additionally, both isomiRs and paralogous/orthologues miRNAs
      were implicated in 5' and 3' ends (especially 3' ends), nucleotide substitutions,
      and insertions and deletions. Generally, multiple isomiRs can be produced from a
      single miRNA locus, but most of them had lower enrichment levels, and only
      several dominant isomiR sequences were detected. These dominant isomiR groups
      were always stable, and one of them would be selected as the most abundant miRNA
      sequence in specific animal species. Some isomiRs might be consistent to miRNA
      sequences in some species but not the other. Homologous miRNAs were often
      detected in similar isomiR repertoires, and showed similar expression patterns,
      while dominant isomiRs showed complex evolutionary patterns from miRNA sequences
      across the animal kingdom. These results indicate that the phenomenon of multiple
      isomiRs is not a random event, but rather the result of evolutionary pressures.
      The existence of multiple isomiRs enables different species to express
      advantageous sequences in different environments. Thus, dominant sequences emerge
      in response to functional and evolutionary pressures, allowing an organism to
      adapt to complex intra- and extra-cellular events.

PMID- 23856131
TI  - Is CD36 gene polymorphism in region encoding lipid-binding domain associated with
      early onset CAD?
AB  - CD36 is a fatty acid translocase in striated muscle cells and cardiomyocytes.
      Some study suggested that alterations in CD36 gene may be associated with
      coronary artery disease (CAD) risk. The aim of the current study was to compare
      the frequency of CD36 variants in region encoding lipid-binding domain in
      Caucasian patients with early-onset CAD, no-CAD adult controls and neonates. The
      study group comprised 100 patients with early onset CAD. The genetic control
      groups were 306 infants and 40 no-CAD adults aged over 70years. Exons 4, 5 and 6
      including fragments of flanking introns were studied using the denaturing high
      performance liquid chromatography technique and direct sequencing. Changes
      detected in analyzed fragment of CD36: IVS3-6 T/C (rs3173798), IVS4-10 G/A
      (rs3211892), C311T (Thr104Ile, not described so far) in exon 5, G550A (Asp184Asn,
      rs138897347), C572T (Pro191Leu, rs143150225), G573A (Pro191Pro, rs5956) and A591T
      (Thr197Thr, rs141680676) in exon 6. No significant differences in the CD36
      genotype, allele and haplotype frequencies were found between the three groups.
      Only borderline differences (p=0.066) were found between early onset CAD patients
      and newborns in the frequencies of 591T allele (2.00% vs 0.50%) and CGCGCGT
      haplotype (2.00% vs 0.50%) with both IVS3-6C and 591T variant alleles. In
      conclusion, CD36 variants: rs3173798, rs3211892, rs138897347, rs5956, rs143150225
      rs141680676 and C311T do not seem to be involved in the risk of early-onset CAD
      in Caucasian population.

PMID- 23856132
TI  - Mutation spectrum of phenylketonuria in Syrian population: genotype-phenotype
      correlation.
AB  - Characterization of the molecular basis of phenylketonuria (PKU) in Syria has
      been accomplished through the analysis of 78 unrelated chromosomes from 39 Syrian
      patients with PKU. Phenylalanine hydroxylase (PAH) gene mutations have been
      analyzed by using molecular detection methods based on the restriction fragment
      length polymorphism (RFLP), artificial constructed restriction sites (ACRS) PCR
      and direct DNA sequencing. 56.4% of the patients had cPKU. A mutation detection
      rate of 79.49% was achieved and sixteen different mutations were found: missense
      56.25%, splice site 37.5%, and frameshift 6.25%. The predominant mutation in this
      population sample was p.R261Q G>A, p.F55>Lfs and p.R243Q G>A. No mutation in six
      PKU patients was observed. In 57.9% of patient genotypes, the metabolic phenotype
      could be predicted. The identification of the mutations in the PAH gene and the
      genotype-phenotype correlation should facilitate the evaluation of metabolic
      phenotypes, diagnosis, implementation of optimal dietary therapy, and
      determination of prognosis in the patients and genetic counseling for the
      patient's relatives.

PMID- 23856134
TI  - [Gender-determinant factors in contraception: design and validation of a
      questionnaire].
AB  - OBJECTIVES: To design and validate a questionnaire for young women on gender
      determinant factors in contraception. METHOD: A questionnaire was developed from
      conversations with young women attending contraception clinic in the Health
      Promotion Municpal Centre, Zaragoza. A total of 200 young women between the ages
      of 13 and 24 self-completed the questionnaire, with only one no response. Several
      items were analysed: reliability, using Cronbach's alpha coefficient, and
      construct validity by analysis of the main components with eigenvalues above 1,
      and Quartimax rotation with Kaiser normalisation. RESULTS: The questionnaire
      contained 36 items and took 10minutes to self-complete. There was good internal
      consistency, with a Cronbach's alpha 0,853. Twelve factors were established with
      an explanation of 61.42% variance, and three descriptive lines: relationship
      dimension ("submissive attitude", "blind attitude", "let go due to affection",
      "dominant partner"), gender identity ("maternity as identity", "non-idealised
      maternity", "traditional role", "insecurity", "shame") and caring. CONCLUSIONS:
      This questionnaire enabled gender determinant-factors that take part in
      contraception to be identified, and will be useful to find out how the different
      ways of relating between the sexes influence the problems of sexual and
      reproductive health in young women in our environment.

PMID- 23856133
TI  - Hereditary premature closure of a coronal suture in the Abraham Lincoln family.
AB  - The most easily recognized facial features of unilateral premature closure of a
      coronal suture in the skull are an upward arching of the superior orbital rim and
      a smaller face on the involved side. Photographs indicate that at least 9
      individuals over 5 generations of the Abraham Lincoln family showed this anomaly.

PMID- 23856135
TI  - [Dropped head syndrome as a first sign of amyotrophic lateral sclerosis].

PMID- 23856136
TI  - [Prognosis related clinical and molecular factors in malignant pleural
      mesothelioma].
AB  - OBJECTIVE: To identify potential prognosis related clinical and molecular factors
      in malignant pleural mesothelioma (MPM). METHODS: Seventy-nine patients with MPM
      treated in Beijing Cancer Hospital from June 1996 to May 2012 were enrolled in
      this study. Clinical and pathological data were collected, including age, gender,
      smoking status, treatment, response, and molecular biomarkers such as thymidylate
      synthetase (TS) expression, echinoderm microtubule-associated protein-like 4
      anaplastic lymphoma kinase (EML4-ALK) gene rearrangement. The primary endpoint
      was overall survival (OS). SPSS 16.0 statistical analysis software was used for
      univariate analysis. The expression of TS was detected by immunohistochemistry
      (IHC). Fluorescence in situ hybridization (FISH) was performed to detect EML4-ALK
      gene rearrangement. Efficacy of the chemotherapy regimen including pemetrexed was
      analyzed with these molecular biomarkers. RESULTS: The median survival time (MST)
      of all patients was 15.5 months (95% CI: 10.6 - 20.4). Univariate survival
      analysis revealed that treatment factors including receiving operation, systemic
      chemotherapy, pemetrexed-based chemotherapy and capability of receiving second
      (or above) line chemotherapy were significantly related with OS. The MST of
      patients receiving operation was 5.4 months (95% CI: 3.6 - 7.3), significantly
      shorter than the 17.7months (95% CI: 11.8 - 23.5) in those who didn't receive
      operation (P = 0.030). Patients receiving systemic chemotherapy had a longer MST
      of 18.0 months (95% CI: 12.3 - 23.8) as compared to the 7.9 months (95% CI: 1.1 -
      14.7) in those who didn't (P = 0.001). The MST of pemetrexed-based chemotherapy
      was 21.9 months (95% CI: 14.1-29.7) compared with 8.8 months (95% CI: 4.2 - 13.4)
      of regimens without pemetrexed (P = 0.000). For patients capable of receiving
      second (or above) line chemotherapy the MST was longer (21.0 months, 95% CI: 12.7
      - 29.3) than those who could not (12.1 month, 95% CI: 6.4 - 17.8 month), P =
      0.022. For the 42 patients treated with pemetrexed-based chemotherapy, the
      objective response rate (ORR) was 33.3% (14/42), the disease control rate (DCR)
      was 78.6% (33/42), the median progression-free survival (PFS) was 4.8 months (95%
      CI: 3.6 - 6.0) and MST was 21.9 months (95% CI: 14.1 - 29.7). Twenty-nine
      patients provided adequate specimens for detection of TS expression and 6 cases
      (20.7%) were positive. EML4-ALK gene rearrangement was studied in 32 patients and
      6 (18.8%) were positive. TS expression was found to be inversely related to PFS
      of pemetrexed-based chemotherapy (P = 0.041). The MST was 19.6 months (95% CI:
      6.0 - 7.9) in EML4-ALK-positive patients and 9.57 months (95% CI: 2.7 - 4.3) in
      negative ones (P = 0.159). CONCLUSIONS: Systemic chemotherapy especially
      pemetrexed-based regimen was proved to be a superior option for MPM with a
      significantly prolonged OS. Correlation between TS expression or EML4-ALK
      rearrangement and outcome of pemetrexed-based chemotherapy for MPM may contribute
      to future individualized treatment, which needs further validation from large
      scale prospective studies.

PMID- 23856137
TI  - [The effect of continuous renal replacement therapy on the outcome of severe
      pneumonia in patients receiving long-term immunosuppressants].
AB  - OBJECTIVE: To investigate the effect of continuous renal replacement therapy
      (CRRT) on the outcome of severe pneumonia in patients receiving long-term
      immunosuppressants. METHODS: Thirty-four patients, who had been treated with long
      term immunosuppressants, were admitted for severe pneumonia. After admission, the
      dose of immunosuppressants including glucocorticoids was decreased, and the
      patients were divided into 2 groups: antibiotic treatment group (n = 16) and
      antibiotic + CRRT treatment group (n = 18). Before and after treatment, the
      changes of the patients' condition, chest CT and blood gas analysis were
      monitored. Biomarkers including C-reactive protein (CRP), interferon-gamma (IFN
      gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      interleukin-8(IL-8), white blood cell and neutrophil counts were determined.
      RESULTS: After treatment, the levels of CRP[(109 +/- 24) vs (40 +/- 13) mg/L],
      IFN-gamma [(151 +/- 28) vs (42 +/- 12) ng/L], TNF-alpha [(301 +/- 45) vs (118 +/-
      28) pg/L], IL-6 [(214 +/- 45) vs (76 +/- 23) pg/L], IL-8[(590 +/- 121) vs (159 +/
      60) pg/L], white blood cell count [(14.3 +/- 5.7)*109/L vs (8.5 +/- 2.7)*109/L],
      and neutrophil percentage [(91.3 +/- 3.1)% vs (75.3 +/- 2.6)%] decreased
      significantly in the antibiotic + CRRT group (P < 0.05) as compared to the
      antibiotic treatment group. In the antibiotic + CRRT group, blood gas showed
      significant improvement in pH [(7.30 +/- 0.12) to (7.37 +/- 0.18)], SaO2 [(80.6
      +/- 7.6)% to (91.9 +/- 7.3)%] and PaO2 (41 +/- 6) mm Hg (1 mm Hg = 0.133 kPa) to
      (71 +/- 9) mm Hg. The patients' condition and chest CT abnormalities also
      improved more rapidly in the antibiotic + CRRT group. The 6-month survival was
      increased by 12.9% in the antibiotic + CRRT group as compared to the antibiotic
      group (P < 0.05). CONCLUSION: CRRT is effective in clearance of inflammatory
      mediators and may increase survival of severe pneumonia patients receiving long
      term treatment of immunosuppressants.

PMID- 23856138
TI  - [A comparison of clinical features between patients with idiopathic pulmonary
      fibrosis combined with emphysema and without emphysema].
AB  - OBJECTIVE: To investigate the differences of clinical features, pulmonary
      function tests, chest imaging and prognosis between patients with idiopathic
      pulmonary fibrosis (IPF) combined with emphysema and without emphysema. METHODS:
      Of the 117 patients diagnosed as IPF for the first time in the First Affiliated
      Hospital of China Medical University from January 2002 to January 2007, 23 cases
      met the diagnostic criteria for combined pulmonary fibrosis and emphysema (CPFE).
      Thirty-three cases with isolated IPF from 2002 to 2003 were selected as the
      control group. Clinical characteristics, pulmonary function indexes, PaO2,
      bronchoalveolar lavage fluid (BALF) results and survival time were
      retrospectively analyzed and compared between the 2 groups. RESULTS: The smoking
      indexes (pack-years)were significantly higher in the CPFE group (28 +/- 18)
      compared with the IPF group (18 +/- 16), t = 2.10, P < 0.05. No significant
      difference was observed between the 2 groups in terms of age, gender and the
      percentage of smokers. The CPFE group showed significantly lower FEV1/FVC% [(77
      +/- 7)%, (83 +/- 8)%, t = 3.55, P < 0.05] and D(L)CO% pred [(44 +/- 12)%, (54 +/-
      16)%, t = 2.48, P < 0.05] compared to those of the IPF group, while TLC%pred was
      significantly higher in the CPFE group [(77 +/- 11)%, (64 +/- 12)%, t = 3.93, P <
      0.05]. VC% pred and PaO2 showed no significant difference between the 2 groups.
      The total cell count, the percentages of macrophages, neutrophils, lymphocytes
      and eosinophils in BALF showed no significant difference between the 2 groups.
      There was no significant difference in median survival time between the 2 groups.
      CONCLUSION: Smoking was an important risk factor for IPF combined with emphysema.
      The pulmonary function of IPF combined with emphysema is characterized by a mild
      abnormality in the lung volume but a significant decrease in the diffusing
      capacity. Combined emphysema has no influence on the survival time of patients
      with IPF.

PMID- 23856139
TI  - [A comparison of ventilation/perfusion single photon emission CT and CT pulmonary
      angiography for diagnosis of pulmonary embolism].
AB  - OBJECTIVE: To assess the diagnostic accuracy of ventilation/perfusion (V/Q)
      single photon emission CT (SPECT) as compared to computed tomographic pulmonary
      angiography (CTPA) for pulmonary embolism (PE). METHODS: In this prospective
      multicenter study, 111 patients in whom acute or sub-acute PE was clinically
      confirmed or suspected were enrolled. The patients underwent one-day method V/Q
      lung scan (including SPECT and planar imaging) within 3 days before and after
      completion of CTPA. The European Association of Nuclear Medicine (EANM)
      guidelines for ventilation/perfusion scintigraphy (2009) reference was used as
      the evaluation criteria of V/Q SPECT imaging. The refined modified prospective
      investigation of pulmonary embolism diagnosis (RM-PIOPED) criteria was used for
      evaluation of planar imaging. According to the direct and indirect signs of PE,
      the imaging of CTPA was evaluated. All patients were followed for at least 6
      months. A diagnosis was finally made by consensus of respiratory physicians,
      radiologists and nuclear medicine physicians based on the clinical data,
      laboratory tests, imaging features and follow-up results. The difference among
      diagnostic methods was evaluated for significance using chi-square test. The
      receiver operator characteristic (ROC) curve was drawn according to the results
      of the 3 diagnostic tests. The area under ROC curve (AUC) was calculated and
      compared. P < 0.05 was considered statistically significant. RESULTS: Among the
      111 patients, PE was confirmed in 80, and excluded in 31. The diagnostic
      sensitivity/specificity/accuracy of V/Q SPECT, planar imaging, and CTPA were
      85.9%/93.5%/88.1%, 75.7%/92.9%/81.4%, and 85.5%/90.0%/86.8%, respectively. By ROC
      curve analysis, the AUC values of V/Q SPECT, planar imaging and CTPA were 0.898,
      0.838, and 0.877, respectively; with 95% confidence intervals [CI] 0.831 to
      0.966, 0.759 to 0.917, and 0.801 to 0.954, respectively. The area of the fitted
      smooth ROC curve was statistically significant (P < 0.05) as compared with the
      area under the reference line. CONCLUSION: The results indicate that SPECT V/Q
      imaging is superior to V/Q planar scan and CTPA in the diagnosis of PE.

PMID- 23856140
TI  - [The treatment outcomes of 21 cases of rapidly growing mycobacteria related
      pulmonary disease].
AB  - OBJECTIVE: To explore the efficacy of the chemotherapeutic regimen with
      clarithromycin (CTM) and amikacin (AMK) as the main drugs in the therapy of
      rapidly growing mycobacteria (RGM) related pulmonary disease. METHODS: The
      clinical efficacy of 21 patients with RGM related pulmonary disease was
      retrospectively analyzed from January 2008 to October 2011 in Guangzhou Chest
      Hospital. The individual chemotherapeutic regimen was mainly based on
      azithromycin (ATM) 0.5 g/d or CTM 0.5 - 1.0 g/d, AMK 0.4 - 0.6 g/d according to
      the medication history and antimicrobial susceptibility tests. After 6 months of
      treatment, symptomatic improvement, changes of imaging findings, sputum cultures
      and adverse effects were observed. RESULTS: In the 21 cases of RGM related
      pulmonary disease, drug resistance to amikacin (9 cases) and clarithromycin (5
      cases) were relatively low as compared to other antituberculous drugs. Lesions
      involving more than 3 lung fields were seen in 17 cases, cough and phlegm in 21,
      bloody sputum in 18, chest pain and shortness of breath in 15, and fever in 15
      cases. After 2-week treatment, fever disappeared and shortness of breath improved
      in all the cases. Cough and phlegm improved in 12 and bloody sputum improved in
      16 cases. After 6-month treatment, lesion absorption occurred in 12 cases, lung
      cavity became smaller in 9 cases and sputum culture became negative in 8 cases.
      Of the 16 cases sensitive to CTM, 11 was smear-negative, and of the 12 cases
      sensitive to AMK, 11 was smear-negative. Common adverse effects included
      gastrointestinal symptoms, liver damage and blood abnormalities. CONCLUSIONS:
      Patients with RGM related pulmonary disease had low rates of drug resistance to
      CTM and AMK. However, individual chemotherapy regimen based on CTM and AMK showed
      unsatisfactory clinical efficacy. More sensitive drugs combined with potent
      chemotherapy regimen are needed for the treatment of this disease.

PMID- 23856141
TI  - [Expression of miR-29a in serum of patients with pulmonary tuberculosis and
      prediction of its function with bioinformatics analysis].
AB  - OBJECTIVE: To analyze the expression of miR-29a in serum of patients with
      pulmonary tuberculosis, and to predict and analyze function of its target genes
      for further studying of its biological function and regulatory mechanism in
      tuberculosis (TB). METHODS: Fasting venous blood samples were collected from 65
      untreated patients with active pulmonary TB (case group) and 45 healthy controls
      (control group) in the morning, respectively, and then sera were isolated. Total
      RNA was extracted with TRIzol reagent and was further purified. RNA quality was
      measured by gel electrophoresis and ultraviolet spectrophotometer. Nucleic acid
      hybridization and real-time reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) were performed to investigate expression of miR-29a in serum.
      Both TargetSean and PicTar software were used to predict comprehensively target
      genes of miR-29a and their intersection was regarded as target genes of miR-29a.
      Gene ontology of target genes was analyzed with DAVID database and three category
      annotations were extracted, respectively. GO overrepresentation was further
      analyzed by BINGO of Cytoscape. Enriched pathways of target genes were analyzed.
      RESULTS: The hybridization result showed that miR-29a was increased in serum of
      the case group (854 +/- 93) compared to the control group (80 +/- 22) (t = 3.541,
      P < 0.05). The PCR result showed that compared to the control group (0.18 +/-
      0.07), miR-29a was increased in serum of the case group (1.35 +/- 0.62) (t =
      2.987, P < 0.05). The target genes were mainly involved in biological processes
      including regulation of transcription, molecular function including metal ion
      binding, and cellular components including extracellular matrix, respectively. In
      the KEGG pathway, the target gene set was significantly enriched in the 7
      signaling pathways including adhesion, ECM-receptor interaction and so on. In the
      PANTHER pathway, the gene set mostly existed in integrin signaling pathway,
      cadherin signaling pathway and Wnt signaling pathway. CONCLUSIONS: Level of miR
      29a was increased significantly in serum of patients with active pulmonary
      tuberculosis. Target genes of miR-29a were mainly involved in biological
      processes including cell adhesion, regulation of transcription and so on.

PMID- 23856142
TI  - [The effect of Bcl-2 gene silencing on the sensitivity of cell line A549 to
      chemotherapeutic drugs].
AB  - OBJECTIVE: To investigate the effects of miRNA-mediated down-regulation of the
      Bcl-2 gene on the chemotherapeutic sensitivities and mRNA transcriptions of
      sensitivity associated genes in human lung adenocarcinoma cell line A549 cells,
      and therefore to provide experimental data for improving the chemotherapeutic
      effects on non-small cell lung cancer (NSCLC). METHODS: The miRNA recombinant
      plasmid targeting to human Bcl-2 gene was designed, synthesized and stably
      transferred into A549 cells by lipofectin technique as the experiment group. The
      transcription of Bcl-2 mRNA was detected by reverse transcription-polymerase
      chain reaction (RT-PCR) by agarose gel electrophoresis, real-time PCR, and the
      protein level of Bcl-2 was measured by Western blot to confirm the function of
      miRNA plasmid. The cell proliferation was examined by methyl thiazolyl
      tetrazolium (MTT) assay. Cell cycle was measured by flow cytometry. Drug
      sensitivities of A549 cells to etoposide, 5-fluorouracil, cisplatin, adriamycin,
      vincristine, paclitaxel and navelbine were analyzed by MTT assay. The mRNA
      expressions of excision repair cross-complementing gene 1 (ERCC1), thymidylate
      synthase (TYMS), Class III beta-tubulin, topoisomerase 2 alpha (TOP2alpha) genes
      were detected by RT-PCR and real-time PCR. RESULTS: The recombinant miRNA plasmid
      was successfully synthesized and stably transferred into A549 cells. The
      transcription of Bcl-2 mRNA dramatically decreased by 98.1% in the experiment
      group (RQ = 0.002 +/- 0.001) compared to that in the negative control group (RQ =
      0.104 +/- 0.003) by real-time PCR (t = 98.70, P < 0.05); and the protein level of
      Bcl-2 in the experiment group decreased by 57.6% by Western blot (t = 7.66, P <
      0.05). The cell cycle profile showed that the low expression of Bcl-2 gene led to
      A549 cell cycle arrest at G1-phase. The results of MTT showed that the growth of
      A549 cells in the experiment group was markedly inhibited. The sensitivities of
      A549 cells to etoposide, cisplatin, paclitaxel, and navelbine were significantly
      enhanced [IC50 values in the experiment group were (107.3 +/- 0.1) mg/L, (7.7 +/-
      0.6) mg/L, (11.5 +/- 1.9) mg/L and (10.8 +/- 1.6) mg/L; IC50 values in the
      negative control group were (145.8 +/- 0.1) mg/L, (60.7 +/- 1.4) mg/L, (80.6 +/-
      1.7) mg/L and (20.6 +/- 1.7) mg/L], the respective t values being 655.33, 108.04,
      82.16 and 12.48, all P < 0.05. The mRNA level of ERCC1, TYMS, and TOP2alpha genes
      in the experiment group decreased by 99.6%, 92.9% and 96.1% respectively, but
      Class III beta-tubulin mRNA increased by 122% compared to the negative control
      group (1.154 +/- 0.008, 0.520 +/- 0.009), the respective t values being 689.79,
      689.37, 768.04 and 160.07, all P < 0.05. CONCLUSION: Targeting to inhibit
      antiapoptotic mitochondrial gene Bcl-2 expression in A549 cells specifically
      decreased the mRNA of ERCC1, TYMS, and TOP2alpha genes, and significantly
      increased the sensitivities of A549 cells to chemotherapeutic agents such as
      etoposide, cisplatin, paclitaxel and navelbine.

PMID- 23856143
TI  - [Detection of pncA mutation associated with pyrazinamide resistance in
      Mycobacterium tuberculosis by high-resolution melting cure analysis].
AB  - OBJECTIVE: To evaluate the application of a high-resolution melting (HRM) curve
      analysis for rapid detection of pyrazinamide resistance in Mycobacterium
      tuberculosis (M. tuberculosis). METHODS: Clinical isolates of M. tuberculosis
      were collected from Shenzhen from 2007 - 2009 and pncA mutations were
      characterized by sequence analysis. HRM analysis method was established and used
      to determine pncA gene mutation in 49 pncA mutant isolates and 78 wild type
      isolates. BCATEC MGIT 960 was used as the standard method to evaluate application
      of the HRM curve. RESULTS: Among 49 pncA mutant isolates, 48 isolates were
      characterized as mutant and 1 isolate with double point mutations misclassified
      as wild type by using HRM detection. In 78 wild type isolates, HRM found 6 mutant
      isolates. Using the BCATEC MGIT 960 to detect pyrazinamide drug susceptibility,
      62 isolates were found resistant and 65 were susceptible. Among the 62 resistant
      strains by HRM results 53 strains were resistant, and among the 65 susceptible
      stains by HRM results 64 were susceptible. Compared to the results of BACTEC MGIT
      960, the sensitivity and specificity of HRM were 85.5% (53/62) and 98.5% (64/65),
      respectively. The Youden index was found to be 0.840. CONCLUSIONS: The results
      showed a good correlation between HRM curve analysis and BACTEC MGIT 960. HRM
      curve analysis is a rapid and accurate method that can be used as a screening
      test for identification of resistance to pyrazinamide.

PMID- 23856144
TI  - [The pilot study of the effect of paclitaxel by local application on scar
      formation after airway injury in rabbits].
AB  - OBJECTIVE: To investigate the effect of local application of paclitaxel on airway
      scar formation after airway injury in rabbits. METHODS: Forty New Zealand rabbits
      were randomly divided into four groups, negative control group (n = 10), saline
      control group (n = 10), group I (n = 10), group II (n = 10). All rabbits received
      tracheotomy. In negative control group, the specimens were harvested for
      histological examination and immunohistochemical analysis immediately after
      tracheotomy;in other three groups, rabbits received airway injury after
      tracheotomy. In group I and group II, 0.4 mg/ml and 1.0 mg/ml paclitaxel was
      applied locally in injured airway segment for 3 minutes after airway injury. The
      normal saline was used in control group for 3 minutes. The animals were killed in
      21 days after operation. The specimens were harvested for histological
      examination and immunohistochemical analysis. Transmission electron microscopy
      was employed to observe the ultrastructure of paclitaxel-induced apoptotic cells.
      RESULTS: The degree of stenosis in group I and group II were significantly
      decreased compared to those in saline control group [saline control group (59 +/-
      13)%, group I (27 +/- 8)%, group II (22 +/- 7)%]. Histological examination showed
      fibroblast cells and inflammatory cells in group I and group II were
      significantly fewer than in saline control group. The TGF-beta1 positive cells
      and VEGF positive cells in group I and group II were significantly decreased
      compared to those in saline control group (P < 0.05). Paclitaxel-induced cell
      apoptosis and injured cell organs were observed by transmission electron
      microscopy. CONCLUSIONS: Local application of paclitaxel inhibits airway scar
      formation after airway injury in rabbit model, and the inhibition is dose
      dependent. Paclitaxel may have a therapeutic potential for the treatment of
      airway stenosis caused by endotracheal intubation, tracheotomy or implantation of
      airway stents.

PMID- 23856145
TI  - [Research progress of body fluid proteomics in diagnosis of tuberculosis].

PMID- 23856146
TI  - [Progress in electrical stimulation on upper airway dilating muscles for
      treatment of obstructive sleep apnea].

PMID- 23856147
TI  - [Progress of research on pressurized metered dose inhalers].

PMID- 23856148
TI  - [Diffuse alveolar hemorrhage after hematopoietic stem cell transplantation].

PMID- 23856149
TI  - [Sleep apnea hypopnea syndrome may be an important cause of chronic cough].

PMID- 23856150
TI  - Validity and reliability of the Berg Balance Scale for community-dwelling persons
      with lower-limb amputation.
AB  - OBJECTIVE: To evaluate the validity and reliability of the Berg Balance Scale
      (BBS) for use in people with lower-limb amputation. DESIGN: Cross-sectional
      study. SETTING: Research laboratory. PARTICIPANTS: Individuals (N=30; age, 54+/
      12y; 20 men) with unilateral transtibial (n=13), unilateral transfemoral (n=14),
      or bilateral (n=3) lower-limb amputation of dysvascular (n=7), traumatic (n=14),
      infectious (n=6), or congenital (n=3) origin. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: BBS, 2-minute walk test, L test, Prosthesis Evaluation
      Questionnaire-Mobility Subscale, Activities-specific Balance Confidence Scale,
      and Frenchay Activities Index; self-reported descriptors were also collected,
      including frequency of prosthesis use, number of falls in 12 months before the
      visit, fear of falling, and daily mobility aid use. RESULTS: The BBS had high
      interrater reliability (intraclass correlation coefficient =.945) and internal
      consistency (alpha=.827). Relations between the BBS scores and those of other
      outcome measures were all statistically significant (P<=.001). Significant group
      differences in BBS scores were observed for fear of falling (P=.008) and mobility
      aid use (P<.001), but not for multiple (>=2) falls in the previous 12 months
      (P=.381). BBS items involving reaching forward, turning 360 degrees , tandem
      standing, and standing on 1 leg had relatively greater frequencies of lower
      scores across participants. CONCLUSIONS: The BBS appears to be a valid and
      reliable clinical instrument for assessing balance in individuals with lower-limb
      amputation, but it may not be able to discriminate between individuals with
      greater or lesser fall risk. Limitations in prosthetic motion and control may be
      responsible for the challenges experienced on items of lower performance. Future
      studies would be useful to assess the responsiveness of the BBS to interventions
      aimed at improving balance in individuals with lower-limb amputation.

PMID- 23856151
TI  - Impact of a wheelchair education protocol based on practice guidelines for
      preservation of upper-limb function: a randomized trial.
AB  - OBJECTIVES: To determine if strict use of the Paralyzed Veterans of America's
      Clinical Practice Guidelines for Preservation of Upper Limb Function affects
      wheelchair setup, selection, propulsion biomechanics, pain, satisfaction with
      life, and participation of individuals with new spinal cord injuries (SCIs).
      DESIGN: Single blinded, randomized controlled trial. SETTING: Model SCI systems
      rehabilitation facility and community. PARTICIPANTS: Volunteer sample of manual
      wheelchair users with new SCIs (N=37). INTERVENTION: The intervention group was
      strictly educated on the clinical practice guideline by a physical therapist and
      an occupational therapist in an inpatient rehabilitation facility. The standard
      of care group received standard therapy services. MAIN OUTCOME MEASURES:
      Comparison of wheelchair setup, selection, propulsion biomechanics, pain, and
      Satisfaction With Life Scale and Craig Handicap Assessment and Reporting
      Technique scores at the time of discharge from inpatient rehabilitation and at 6
      months and 1 year postdischarge. RESULTS: Participants in the intervention group
      pushed on tile with significantly lower push frequency (P=.02) at the discharge
      visit. On the ramp, the intervention group used a significantly larger push
      length (P=.03) across all time points. No significant differences were found
      between groups related to wheelchair setup, selection, pain, satisfaction with
      life, and participation. CONCLUSIONS: The intervention group showed better skills
      on key wheelchair propulsion biomechanics variables related to upper-limb health.
      Use of a structured education program may be an effective method of educating new
      manual wheelchair users to prevent the development of upper-limb impairments in
      an inpatient setting. Additional follow-up testing is necessary to determine
      whether the differences seen in propulsion skills translate into decreased pain
      and improved quality of life in the long term.

PMID- 23856152
TI  - Disorders of consciousness: outcomes, comorbidities, and care needs.
AB  - Over the last decade, research on patients with disorders of consciousness (DOC)
      has suggested that their prognosis for functional recovery early after injury is
      surprisingly positive, particularly for those with traumatic etiologies; that
      meaningful recovery proceeds for longer intervals than previously appreciated;
      and that such individuals are often medically complex and challenging to manage.
      However, access to intensive specialty rehabilitation is limited for most
      individuals with DOC in the United States. The evolving understanding of DOC
      calls for a reconsideration of appropriate models of care. This collection of
      articles provides insight into the functional recovery of individuals with DOC,
      new tools for assessing prognosis, and the patterns of comorbidity that
      complicate the recovery process. In addition, models of care from the United
      States and Europe that attempt to address the needs of patients as well as their
      caregivers are presented. 

PMID- 23856154
TI  - Orbital floor restoration with traction of the infraorbital nerve using a vessel
      loop in posterior orbital floor fractures.
AB  - BACKGROUND: The authors retracted the infraorbital nerve (ION) using a vessel
      loop to explore the orbital floor fracture site and analysed when the traction of
      the ION was needed. METHODS: In ninety-one patients, the location of the fracture
      according to its position relative to the infraorbital groove, the location of
      the infraorbital groove from the midpoint of the orbital floor, and involvement
      of the ION in the fracture site were recorded retrospectively from computed
      tomography scans. An analysis of any associations between the traction of ION and
      the location of the fracture and ION passage was performed. RESULTS: Traction of
      the ION was performed in 14 cases, of which 10 cases had involvement of the ION
      in the fracture site and 4 cases did not. All of them were posterior fractures.
      In 51 cases with posterior fractures, the ION passage in patients who had ION
      traction was statistically located more medially (0.50 +/- 1.19 mm) than in
      patients who had no traction (2.38 +/- 1.12 mm) (p < 0.05). CONCLUSION: The ION
      may interfere with the exposure of the fracture site in a posterior orbital floor
      fracture with the involvement of the ION in the fracture site and a medially
      located ION passage.

PMID- 23856153
TI  - Proton pump inhibitors and the risk of hospitalisation for community-acquired
      pneumonia: replicated cohort studies with meta-analysis.
AB  - OBJECTIVE: Previous observational studies suggest that the use of proton pump
      inhibitors (PPIs) may increase the risk of hospitalisation for community-acquired
      pneumonia (HCAP). However, the potential presence of confounding and protopathic
      biases limits the conclusions that can be drawn from these studies. Our objective
      was, therefore, to examine the risk of HCAP with PPIs prescribed prophylactically
      in new users of non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: We formed
      eight restricted cohorts of new users of NSAIDs, aged >=40 years, using a common
      protocol in eight databases (Alberta, Saskatchewan, Manitoba, Ontario, Quebec,
      Nova Scotia, US MarketScan and the UK's General Practice Research Database
      (GPRD)). This specific patient population was studied to minimise bias due to
      unmeasured confounders. High-dimensional propensity scores were used to estimate
      site-specific adjusted ORs (aORs) for HCAP at 6 months in PPI patients compared
      with unexposed patients. Fixed-effects meta-analytic models were used to estimate
      overall effects across databases. RESULTS: Of the 4,238,504 new users of NSAIDs,
      2.3% also started a PPI. The cumulative 6-month incidence of HCAP was 0.17% among
      patients prescribed PPIs and 0.12% in unexposed patients. After adjustment, PPIs
      were not associated with an increased risk of HCAP (aOR=1.05; 95% CI 0.89 to
      1.25). Histamine-2 receptor antagonists yielded similar results (aOR=0.95, 95% CI
      0.75 to 1.21). CONCLUSIONS: Our study does not support the proposition of a
      pharmacological effect of gastric acid suppressors on the risk of HCAP.

PMID- 23856155
TI  - Enhanced protective immune responses against Salmonella Enteritidis infection by
      Salmonella secreting an Escherichia coli heat-labile enterotoxin B subunit
      protein.
AB  - Escherichia coli heat-labile enterotoxin B subunit (LTB) protein is a potent
      mucosal adjuvant. In this study, the effect of an attenuated Salmonella secreting
      LTB protein as an adjuvant strain (JOL1228) for a live Salmonella Enteritidis
      (SE) vaccine candidate (JOL919) was evaluated. In a single immunization
      experiment, chickens immunized with a mixture of JOL919 (5 parts) and JOL1228 (1
      part) showed enhanced mucosal and cellular immune responses and efficient
      protection against salmonellosis as compared to those unimmunized control
      chickens. In further analysis, chickens were primed at one day of age and were
      boosted at the fifth week of age to prolong immune responses and to maximize the
      protection efficacy against salmonellosis. The immunized groups B (prime and
      booster with JOL919), C (prime with JOL919-JOL1228 mixture and booster with
      JOL919), and D (prime and booster with JOL919-JOL1228 mixture) showed
      significantly higher humoral and cellular immune responses as compared to those
      in the unimmunized control group A. In addition, immunized groups C and D showed
      fewer gross lesions in the liver and spleen and a lower number of SE-positive
      organs, with the lowest bacterial counts in the SE challenge strain as compared
      to the control group. These results indicate that SE vaccination with the LTB
      strain can have an adjuvant effect on the vaccine candidate by enhancing immune
      responses, and that a prime-boost strategy with the addition of the adjuvant
      strain can efficiently protect birds against salmonellosis. 

PMID- 23856156
TI  - Lipofibroadenoma of the thymus: a case report.
AB  - We observed an unusual case of Lipofibroadenoma (LFA) in the anterior mediastinum
      with a 21-year-old man, who was detected with a mass on a chest X-ray scan for
      one month. Thymothymectomy was then performed and the mass was excised
      completely, in which the tumor was histologically composed of epithelial cells,
      lymphocytes, mature adipose and fibrous tissue. Within the tumor, the fat cells
      was distributed singly or multifocally under the ground of fibro tissue with
      hyaline degeneration, and the epithelial cells were arranged as crack structure
      with lymphocytes infiltrated sparsely. By immunohistochemical staining assay, the
      epithelial cells were positive for AE1/AE3 and CK19, and the lymphocytes were CD3
      and CD20 positive. Based on the histological characters, a diagnosis of LFA was
      made, and the total follow-up period was determined to be forty six months. The
      final repeated CT scan revealed no recurring or residual lesions were detected
      during the post-surgical course. VIRTUAL SLIDE: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1500429801911703.

PMID- 23856157
TI  - Maternal transfer of immunity in scallop Chlamys farreri and its trans
      generational immune protection to offspring against bacterial challenge.
AB  - Maternal immunity plays a crucial role in protecting the offspring at early
      stages of life and contributes a trans-generational effect on the offspring's
      phenotype. In the present study, maternal transfer of immunity and its trans
      generational effect on offspring in scallop Chlamys farreri were investigated.
      The proteins including CfLGBP, CfLBP/BPI, CfLYZ and CfCu/Zn-SOD existed in the
      scallop eggs with high level while CfLec-3 was not detected. In contrast, the
      mRNA levels of these proteins were extremely low except that of CfCu/Zn-SOD. The
      protein extracts of scallop eggs exhibited remarkable agglutination activity and
      bactericidal effect against gram-negative bacteria Escherichia coli and Vibro
      anguillarum, and fungi Pichia pastoris. When the maternal scallops were
      stimulated with heat-killed V. anguillarum, the mRNA levels of CfLBP/BPI and
      CfLYZ in their offspring were expressed significant higher in D-shaped larvae.
      Furthermore, the protein levels of CfLBP/BPI and CfCu/Zn-SOD in the offspring of
      maternal immune stimulation group were higher than that of control at almost all
      the developmental stages, while the level of CfLec-3 and CfLYZ was higher than
      that of control just in eggs or trochophore, respectively. A significant
      enhancement of Cu/Zn-SOD and antibacterial activities was also observed in eggs,
      4-cell embryos and trochophore of offspring from immune stimulated mother
      scallops. Moreover, the mortality of offspring from the immune stimulated mother
      scallops was significantly lower than that of control after bacterial challenge,
      especially in trochophore. The results indicated that scallop eggs or embryos
      received maternal derived immune competence to defense against the invading
      pathogens, and the maternal scallops received an immune stimulation endowed their
      offspring with a trans-generational immune capability to protect them against
      infections effectively. 

PMID- 23856158
TI  - Stress granules form in Brachionus manjavacas (Rotifera) in response to a variety
      of stressors.
AB  - Many eukaryotes share a common response to environmental stresses. The responses
      include reorganization of cellular organelles and proteins. Similar stress
      responses between divergent species suggest that these protective mechanisms may
      have evolved early and been retained from the earliest eukaryotic ancestors. Many
      eukaryotic cells have the capacity to sequester proteins and mRNAs into transient
      stress granules (SGs) that protect most cellular mRNAs (Anderson and Kedersha,
      2008). Our observations extend the phylogenetic range of SGs from
      trypanosomatids, insects, yeast and mammalian cells, where they were first
      described, to a species of the lophotrochozoan animal phylum Rotifera. We focus
      on the distribution of three proteins known to be associated with both ribosomes
      and SG formation: eukaryotic initiation factors eIF3B, eIF4E and T-cell
      restricted intracellular antigen 1. We found that these three proteins co
      localize to SGs in rotifers in response to temperature stress, osmotic stress and
      nutrient deprivation as has been described in other eukaryotes. We have also
      found that the large ribosomal subunit fails to localize to the SGs in rotifers.
      Furthermore, the SGs in rotifers disperse once the environmental stress is
      removed as demonstrated in yeast and mammalian cells. These results are
      consistent with SG formation in trypanosomatids, insects, yeast and mammalian
      cells, further supporting the presence of this protective mechanism early in the
      evolution of eukaryotes. 

PMID- 23856159
TI  - Sustained release of platelet-derived growth factor and vascular endothelial
      growth factor from silk/calcium phosphate/PLGA based nanocomposite scaffold.
AB  - To exploit the therapeutic potential of growth factors in tissue regeneration, it
      is necessary to design a porous scaffold in order to concurrently accommodate
      cells and release angiogenic factors in a controlled manner. In an attempt to
      address these issues, we developed a nanocomposite scaffold based on silk/calcium
      phosphate/PLGA by freeze-drying and electrospinning in order to control the
      release of platelet-derived growth factor (PDGF) and vascular endothelial growth
      factor (VEGF). The highly porous scaffold possessed appropriate chemical and
      physical structure as confirmed by FTIR, XRD, SEM, and Zeta potential analysis.
      Furthermore, the incorporation of PDGF and VEGF in the scaffold was confirmed
      using Raman spectroscopy while their bioactivity was maintained by 82% and 89%
      for up to 28 days, respectively. The release of PDGF was slower than VEGF as
      respected. Additionally, the scaffold could promote proliferation, alkaline
      phosphatase production and attachment of human osteoblast cells. Histological
      examination established new bone matrix formation with neovascularization in the
      angiogenic factors loaded scaffold after 10 weeks of implantation in rabbit
      model. Finally, it was considered that the fabricated nanocomposite could be
      useful for bone tissue engineering applications. 

PMID- 23856160
TI  - Hydrogel blends with adjustable properties as patches for transdermal delivery.
AB  - The effect of different preparation parameters were analyzed with respect to the
      rheological and pharmaceutical characteristics of hydrogel blend patches, as
      transdermal delivery formulation. Mixtures of pectin and gelatin were employed
      for the production of patches, with adjustable properties, following a two-step
      gelation procedure. The first gelation, a thermal one, is trigged by the presence
      of gelatin, whereas, the second gelation, an ionic one, is due to the formation
      of the typical egg box structure of pectin. In particular, the patch structural
      properties were assessed by oscillation stress sweep measurements which provided
      information concerning their viscolelastic properties. In addition, different
      modalities for drug loading were analyzed with respect to drug homogeneous
      distribution; testosterone was employed as model drug for transdermal
      administration. Finally, the performances of the produced transdermal patches
      were studied, in term of reproducibility and reliability, by determination of in
      vitro drug release profiles. 

PMID- 23856161
TI  - Non-covalent functionalization of single-walled carbon nanotubes with modified
      polyethyleneimines for efficient gene delivery.
AB  - Functionalized carbon nanotubes (CNTs) have been recently emerged as important
      class of vectors for delivery of DNA and other biomolecules into various cells.
      In this study, single-walled carbon nanotubes (SWNTs) were functionalized by non
      covalent binding of hydrophobic moieties, which were covalently linked to
      polyethyleneimines (PEIs). PEIs of three molecular weights (25, 10 and 1.8kDa)
      were used. CNTs were functionalized with the PEI series either through
      phospholipid moiety (via a polyethyleneglycol linker) or through directly
      attached long (18 carbons) or intermediate (10 carbons) hydrophobic alkyl
      moieties. All PEI-functionalized CNTs exhibited good stability and dispersibility
      in biological media. Visualizing of functionalized CNTs and lack of aggregation
      were confirmed by atomic force microscopy. The PEI derivatives bound to CNTs
      retained the ability to fully condense plasmid DNA at low N/P ratios and
      substantial buffering capacity in the endosomal pH range. PEI-functionalized CNTs
      exhibited increased transfection efficiency compared to underivatized PEIs up to
      19-fold increase being observed in the functionalized CNT with the smallest PEI
      tested, the smallest hydrophobic attachment moiety tested and no linker. Also PEI
      functionalized CNTs were effective gene delivery vectors in vivo following tail
      vein injection in mice with the largest expression occurring with the vector PEI
      functionalized through a polyethyleneglycol linker.

PMID- 23856162
TI  - Gelatine enhances drug dispersion in alginate bilayer film via the formation of
      crystalline microaggregates.
AB  - In our previous study, a novel alginate-based bilayer film for slow-release wound
      dressings was successfully developed. We found that alginate alone yielded poor
      films; however, the addition of gelatine had significantly enhanced the drug
      dispersion as well as the physical properties. Here, an investigation of the drug
      polymer interactions in the bilayer films was carried out. Drug content
      uniformity test and microscopy observation revealed that the addition of gelatine
      generated bilayer films with a homogenous drug distribution within the matrix.
      The FTIR and XRD data showed an increase in film crystallinity which might infer
      the presence of drug-polymer crystalline microaggregates in the films. DSC
      confirmed the drug-polymer interaction and indicated that the gelatine has no
      effect on the thermal behaviour of the microaggregates, suggesting the
      compatibility of the drug and excipients in the bilayer films. In conclusion, the
      addition of gelatine can promote homogenous dispersion of hydrophobic drugs in
      alginate films possibly through the formation of crystalline microaggregates. 

PMID- 23856163
TI  - Association between total plasma homocysteine level and cognitive functions in
      elderly Egyptian subjects.
AB  - BACKGROUND: High plasma total homocysteine has emerged as a new risk for
      cognitive decline with age. OBJECTIVES: The aim of the present study was to
      examine the association of plasma homocysteine with cognitive performance in
      normal aged Egyptians. SUBJECT AND METHODS: Forty five aged Egyptians subjects
      were included in the study. Their cognitive performance was assessed using Mini
      Mental State Examination MMSE, Addenbrooke's Cognitive Examination (ACE) and
      Clinical Dementia Rating (CDR) scale. Total plasma homocysteine level in fasting
      blood samples was also measured. RESULTS: A statistically significant negative
      association was detected between plasma homocysteine level and age. A
      statistically highly significant inverse association was found between plasma
      tHcy and scores of cognitive assessment in aged subjects after adjustment for
      age, gender, education years and cardiovascular risk factors. No significant
      association was detected between total plasma homocysteine level and sex, blood
      sugar or lipid profile (p>=0.05). CONCLUSION: Elevated tHcy level is an
      independent risk factor for the decline of cognitive performance in normal
      elderly subjects.

PMID- 23856164
TI  - [Bullous cutaneous lesion on the hand of an adolescent].

PMID- 23856165
TI  - Evaluation of Oxford instability shoulder score, Western Ontario shoulder
      instability index and Euroqol in patients with SLAP (superior labral anterior
      posterior) lesions or recurrent anterior dislocations of the shoulder.
AB  - BACKGROUND: Having an estimate of the measurement error of self-report
      questionnaires is important both for assessing follow-up results after treatment
      and when planning intervention studies. Specific questionnaires have been
      evaluated for patients with shoulder instability, but not in particular for
      patients with SLAP (superior labral anterior posterior) lesions or recurrent
      dislocations. The aim of this study was to evaluate the agreement, reliability,
      and validity of two commonly questionnaires developed for patients with shoulder
      instability and a generic questionnaire in patients with SLAP lesions or
      recurrent anterior shoulder dislocations. METHODS: Seventy-one patients were
      included, 33 had recurrent anterior dislocations and 38 had a SLAP lesion. The
      patients filled in the questionnaires twice at the same time of the day (+/- 2
      hours) with a one week interval between administrations. We tested the Oxford
      Instability Shoulder Score (OISS) (range 12 to 60), the Western Ontario Shoulder
      Instability Index (WOSI) (0 to 2100), and the EuroQol: EQ-5D (-0.5 to 1.0) and EQ
      VAS (0 to 100). Hypotheses were defined to test validity. RESULTS: ICC ranged
      from 0.89 (95% CI 0.83 to 0.93) to 0.92 (0.87 to 0.95) for OISS, WOSI, and EQ-VAS
      and was 0.66 (0.50 to 0.77) for EQ-5D. The limits of agreement for the scores
      were: -7.8 to 8.4 for OISS; -339.9 to 344.8 for WOSI; -0.4 to 0.4 for EQ-5D; and 
      17.2 and 16.2 for EQ-VAS. All questionnaires reflect the construct that was
      measured. The correlation between WOSI and OISS was 0.73 and ranged from 0.49 to
      0.54 between the shoulder questionnaires and the generic questionnaires. The
      divergent validity was acceptable, convergent validity failed, and known group
      validity was acceptable only for OISS. CONCLUSION: Measurement errors and
      limitations in validity should be considered when change scores of OISS and WOSI
      are interpreted in patients with SLAP lesions or recurrent shoulder dislocations.
      EQ-5D is not recommended as a single outcome.

PMID- 23856166
TI  - Triplet-triplet energy transfer in fucoxanthin-chlorophyll protein from diatom
      Cyclotella meneghiniana: insights into the structure of the complex.
AB  - Although the major light harvesting complexes of diatoms, called FCPs
      (fucoxanthin chlorophyll a/c binding proteins), are related to the cab proteins
      of higher plants, the structures of these light harvesting protein complexes are
      much less characterized. Here, a structural/functional model for the "core" of
      FCP, based on the sequence homology with LHCII, in which two fucoxanthins replace
      the central luteins and act as quenchers of the Chl a triplet states, is
      proposed. Combining the information obtained by time-resolved EPR spectroscopy on
      the triplet states populated under illumination, with quantum mechanical
      calculations, we discuss the chlorophyll triplet quenching in terms of the
      geometry of the chlorophyll-carotenoid pairs participating to the process. The
      results show that local structural rearrangements occur in FCP, with respect to
      LHCII, in the photoprotective site. 

PMID- 23856167
TI  - HBV transmission from an occult carrier with five mutations in the major
      hydrophilic region of HBsAg to an immunosuppressed plasma recipient.
AB  - We describe the case of transmission of an HBsAg-negative hepatitis B infection
      to an immunosuppressed patient by plasma donation from an HBsAg-negative subject,
      but with very low serum HBV DNA (about 50 IU/ml) and five mutations in the major
      hydrophilic region of HBsAg.

PMID- 23856169
TI  - Modelling counter-current chromatography using a temperature dependence plate
      model.
AB  - So far, research workers have built several math models of counter-current
      chromatography (CCC), such as cell model, eluting counter-current distribution
      model, continuous-stirred tank reactors model, and probability model. Based on
      plate theory and Van't Hoff equation, a new temperature dependence plate model
      has been established in this paper. When temperature was taken into
      consideration, the error of retention time was significantly reduced. The
      relationship between temperature and partition coefficient K can be summarized
      into linear equations (logK=A-B/T), which can be introduced to the plate model
      where A and B are constant and T is the temperature in Kelvin. K values decreased
      with the increasing temperature. Since resolution values (R) are related to K
      values, the change of temperature finally leads to the change of resolutions
      between different compounds. K values at different temperatures of a certain
      compound in a given system were calculated according to the equation above. New
      program with a temperature parameter was applied in prediction of experimental
      results, which diminished the error in modelling prediction. Besides, it is
      difficult for the CCC work when two compounds have similar K values. However,
      separation can be achieved by changing temperature, which can be directed by this
      new model. 

PMID- 23856168
TI  - Construction and application of an efficient multiple-gene-deletion system in
      Corynebacterium glutamicum.
AB  - Gene deletion techniques are important for modifying Corynebacterium glutamicum,
      the bacterium for industrial production of amino acids. In this study, a novel
      multiple-gene-deletion system for C. glutamicum was developed. The system is
      composed of three plasmids pDTW109, pDTW201 and pDTW202. pDTW109 is a temperature
      sensitive vector which harbors a cat gene under the tacM promoter, a cre gene
      under the tac promoter, an origin oriE for replicating in Escherichia coli, and
      another origin rep(TS) for replicating in C. glutamicum only at low temperatures;
      it has high transformation efficiency in C. glutamicum and can be easily
      eliminated by growing at 37 degrees C. pDTW201 and pDTW202 carry loxp-flanked or
      mutant lox-flanked kan, respectively. This deletion system combines homologous
      recombination and Cre/lox site-specific recombination, could efficiently delete
      the aceE gene from the chromosome of C. glutamicum ATCC13032, ATCC13869 or
      ATCC14067, respectively, and could also delete both genes of aceE and ilvA from
      the chromosome of C. glutamicum ATCC14067. The system is simple and efficient,
      and can be easily implemented for multiple-gene-deletion in C. glutamicum. 

PMID- 23856170
TI  - The association between the PPARgamma2 Pro12Ala polymorphism and nephropathy
      susceptibility in type 2 diabetes: a meta-analysis based on 9,176 subjects.
AB  - BACKGROUND: The polymorphism Pro12Ala in peroxisome proliferator-activated
      receptor-gamma2 gene (PPARgamma2) has been reported to be associated with
      diabetic nephropathy (DN) in some studies, though the results remain
      inconclusive. To explore this relationship between PPARgamma2 Pro12Ala
      polymorphism and the susceptibility for DN, a cumulative meta-analysis was
      performed in this study. METHOD: PubMed, Medline, Embase and Web of Science
      databases have been systematically searched to identify relevant studies. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: 18
      studies were included in this meta-analysis, involving 3,361 cases and 5,815
      controls. The PPARgamma2 Ala12 allele was significantly associated with decreased
      risk of DN based on dominant model (OR=0.778; 95%CI=0.618-0.981;
      Pheterogeneity=0.008; P=0.034). In the stratified analysis by ethnicity,
      significantly decreased risks were found among Caucasians for dominant model
      (OR=0.674; 95%CI=0.500-0.909; Pheterogeneity=0.079; P=0.010), while there was no
      significant association was found in Asians. CONCLUSIONS: The results from the
      present meta-analysis indicated that the Pro12Ala polymorphism in PPARgamma2 gene
      is not a risk factor for DN in type 2 diabetes (T2D). Further large and well
      designed studies are needed to confirm this conclusion. VIRTUAL SLIDES: The
      virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7491348341027320.

PMID- 23856171
TI  - Phonological processing of rhyme in spoken language and location in sign language
      by deaf and hearing participants: a neurophysiological study.
AB  - AIM: Sign languages (SL), like oral languages (OL), organize elementary,
      meaningless units into meaningful semantic units. Our aim was to compare, at
      behavioral and neurophysiological levels, the processing of the location
      parameter in French Belgian SL to that of the rhyme in oral French. PARTICIPANTS
      AND METHODS: Ten hearing and 10 profoundly deaf adults performed a rhyme judgment
      task in OL and a similarity judgment on location in SL. Stimuli were pairs of
      pictures. RESULTS: As regards OL, deaf subjects' performances, although above
      chance level, were significantly lower than that of hearing subjects, suggesting
      that a metaphonological analysis is possible for deaf people but rests on
      phonological representations that are less precise than in hearing people. As
      regards SL, deaf subjects scores indicated that a metaphonological judgment may
      be performed on location. The contingent negative variation (CNV) evoked by the
      first picture of a pair was similar in hearing subjects in OL and in deaf
      subjects in OL and SL. However, an N400 evoked by the second picture of the non
      rhyming pairs was evidenced only in hearing subjects in OL. The absence of N400
      in deaf subjects may be interpreted as the failure to associate two words
      according to their rhyme in OL or to their location in SL. CONCLUSION: Although
      deaf participants can perform metaphonological judgments in OL, they differ from
      hearing participants both behaviorally and in ERP. Judgment of location in SL is
      possible for deaf signers, but, contrary to rhyme judgment in hearing
      participants, does not elicit any N400.

PMID- 23856172
TI  - Combined caffeine and bright light reduces dangerous driving in sleep-deprived
      healthy volunteers: a pilot cross-over randomised controlled trial.
AB  - AIM OF THE STUDY: To explore the effects of caffeine and bright light therapy on
      simulated nighttime driving in sleep-deprived healthy volunteers. PARTICIPANTS
      AND METHODS: Twelve male healthy volunteers aged 20 to 50 years participated in a
      randomized cross-over study of simulated nighttime driving at a sleep laboratory,
      followed by recovery sleep with polysomnography at home. The volunteers received
      variable combinations of caffeine 200mg (C+), caffeine placebo (C-), bright light
      10,000 lux (L+), and bright light placebo<50 lux (L-), in four sessions (C+L+,
      C+L-, C-L+, C-L-), in random order with a wash-out period of 7 days. Treatments
      were given at 1 a.m. and testing was performed at 1:30 a.m., 3 a.m., 4 a.m., and
      6 a.m. Lane drifting was the primary outcome measure. Other measures were
      reaction times, self-rated fatigue, sleepiness and recovery sleep. RESULTS:
      Without treatment, lane drifting increased throughout the night, and objective
      and subjective vigilance declined. Paired comparisons showed that lane drifting
      was significantly worse at 6 a.m. and at 4 a.m. than at 1:30 a.m. There was a
      global treatment effect on lane drifting. Lane drifting at 6 a.m. was
      significantly decreased with C+L+ compared to C-L-. CONCLUSIONS: Bright light
      therapy combined with caffeine administered at 1 a.m. decreased lane drifting by
      healthy volunteers during simulated nighttime driving.

PMID- 23856173
TI  - Discriminating neurological from psychiatric hypersomnia using the forced
      awakening test.
AB  - INTRODUCTION: Sleep inertia refers to the inability to attain full alertness
      following awakening from sleep and is a major component of hypersomnia. As event
      related potentials (ERPs) are correlated to the degree of consciousness, they
      allow exploring information processing in transitional states of vigilance. Their
      modifications during forced awakening (FA) context have been shown to reflect
      sleep inertia. OBJECTIVES: To assess the diagnostic value of a FA test using an
      oddball stimulation protocol during a nap in a representative sample of patients
      with excessive daytime sleepiness (EDS). METHODS: One hundred and seventy three
      patients [30 narcolepsy, 62 idiopathic hypersomnia, 33 sleep apnoea syndrome, and
      48 other (mainly psychiatric) hypersomnia] performed an auditory target detection
      stimulation task during pre-, post-nap wakefulness, and during two successive
      intra-nap FA while the EEG was simultaneously recorded. Both the accuracy of
      target detection and the ERPs were evaluated. ERPs during forced awakening test
      were considered to reflect sleep inertia if they presented with a P300 delay
      and/or sleep negativities (N350/N550). RESULTS: Pre-nap behavior and ERPs were
      normal in all patients. Behavioral results were significantly worse during FA
      than during wakefulness for all groups of patients. P300 latencies were
      significantly delayed on FA conditions in each group of patients except the
      psychiatric group. Sensitivity and specificity for detection of sleep inertia
      were 64% and 94%, respectively, with predictive values of 96% (positive) and 50%
      (negative). CONCLUSIONS: Our results suggest that the FA test could be helpful as
      a diagnostic procedure for discriminating neurological from psychiatric
      hypersomnia.

PMID- 23856175
TI  - Pneumatic evoked potential. Sensory or auditive potential?
AB  - STUDY AIM: In this study, evoked potentials (EPs) to a pneumatic, innocuous, and
      calibrated stimulation of the skin were recorded in 22 volunteers. METHODS: Air
      puff stimuli were delivered through a home-made device (INSA de Lyon, Laboratoire
      Ampere, CHU de Saint-Etienne, France) synchronized with an EEG recording
      (Micromed((r))). RESULTS: A reproducible EP was recorded in 18 out of 22 subjects
      (82% of cases) with a mean latency of about 120-130ms, and maximal amplitude at
      Cz. This EP actually consisted of two components, an auditory and a somatosensory
      one. Indeed, it was significantly decreased in amplitude, but did not disappear,
      when the noise generated by the air-puff was masked. We also verified that a
      stimulation close to the skin but not perceived by the subject was not associated
      with any EP. Conduction velocity between hand and shoulder was calculated around
      25m/s. CONCLUSIONS: This preliminary study demonstrates that pneumatic EPs can be
      recorded in normal volunteers.

PMID- 23856174
TI  - Rapidly progressive amyotrophic lateral sclerosis initially masquerading as a
      demyelinating neuropathy.
AB  - Rare cases of demyelinating neuropathy have been described in association with
      amyotrophic lateral sclerosis (ALS). We report two patients with typical ALS
      whose initial electroneuromyographic (ENMG) presentation could suggest the
      existence of a process of motor nerve fiber demyelination. However, subsequent
      ENMG examinations and the fatal course of the disease in a few months rather
      supported severe ongoing axonal degeneration at the origin of motor nerve
      conduction abnormalities. Repeated examinations could be required to distinguish
      between ENMG features of concomitant demyelinating neuropathy and rapidly
      progressive motor neuron loss in ALS. 

PMID- 23856176
TI  - [Is the sense of verticality vestibular?].
AB  - The vestibular system constitutes an inertial sensor, which detects linear
      (otoliths) and angular (semicircular canals) accelerations of the head in the
      three dimensions. The otoliths are specialized in the detection of linear
      accelerations and can be used by the brain as a "plumb line" coding earth gravity
      acceleration (direction). This property of otolithic system suggested that the
      sense of verticality is supported by the vestibular system. The preeminence of
      vestibular involvement in the sense of verticality stated in the 1900s was
      progressively supplanted by the notion of internal models of verticality. The
      internal models of verticality involve rules and properties of integration of
      vestibular graviception, somaesthesic graviception, and vision. The construction
      of a mental representation of verticality was mainly modeled as a bottom-up
      organization integrating visual, somatosensory and vestibular information without
      any cognitive modulations. Recent studies reported that the construction of
      internal models of verticality is not an automatic multi-sensory integration
      process but corresponds to more complex mechanisms including top-down influences
      such as awareness of body orientation or spatial representations. 

PMID- 23856177
TI  - Catechol-functionalized adhesive nanoparticles as a surface-releasing system.

PMID- 23856178
TI  - Formative research on HAPA model determinants for fruit and vegetable intake:
      target beliefs for audiences at different stages of change.
AB  - Theoretically driven health communications are needed to promote fruit and
      vegetable intake among people at different stages of change. The Health Action
      Process Approach, a clearly specified model and good predictor of fruit and
      vegetable intake, was used as a framework to guide a formative research for the
      development of health messages targeting individuals at either a non-intentional
      or intentional stage of change. A mixed-method approach was used, combining eight
      focus groups (n = 45) and a questionnaire (n = 390). Target beliefs for people at
      both stages were identified under five theoretical constructs (risk perception,
      outcome expectancies, action planning, coping planning and self-efficacy).
      Highlighting health problems due to low fruit and vegetable consumption, health
      benefits, weight reduction and pleasure and enhancing self-efficacy to increase
      fruit and vegetable intake are the main guidelines for designing messages to non
      intenders. For intenders, messages should reassure them of their ability to
      maintain adequate fruit and vegetable consumption, outline specific plans for
      increased consumption, identify barriers such as preparation, forgetting or being
      tired and unwilling to eat fruits and vegetables and suggest strategies to
      overcome them, such as presenting some practical examples on how to include
      fruits and vegetables when eating out. 

PMID- 23856179
TI  - Aboriginal youth suicide in Quebec: the contribution of public policy for
      prevention.
AB  - The high rate of youth suicide in some First Nations villages of Northern Quebec
      is an important public health problem. Based on a six-year field study in three
      villages belonging to the Atikamekw and Anishinabe groups, this paper proposes
      changes in three areas of social policy that could contribute to prevention of
      youth suicide. These three areas are: youth protection, administration of
      justice, and housing. An argument is made first to adapt the youth protection law
      of Quebec and to give greater responsibility to communities in individual cases
      in order to prevent child placement outside the villages. Regarding the
      administration of justice, we suggest initiatives to encourage rapid prosecution
      of crimes on reserves and the adoption of an approach based on reconciliation
      between perpetrator and victim. Finally, we indicate how housing measures could
      help safeguard children's wellbeing given that overcrowding can contribute to
      suicide. The discussion also proposes that these three key changes in social
      policy could be relevant in other Aboriginal communities both within and outside
      of Quebec. 

PMID- 23856180
TI  - Physician assisted suicide: the great Canadian euthanasia debate.
AB  - A substantial majority of Canadians favours a change to the Criminal Code which
      would make it legally permissible, subject to careful regulation, for patients
      suffering from incurable physical illness to opt for either physician assisted
      suicide (PAS) or voluntary active euthanasia (VAE). This discussion will focus
      primarily on the arguments for and against decriminalizing physician assisted
      suicide, with special reference to the British Columbia case of Lee Carter vs.
      Attorney General of Canada. The aim is to critique the arguments and at the same
      time to describe the contours of the current Canadian debate. Both ethical and
      legal issues raised by PAS are clarified. Empirical evidence available from
      jurisdictions which have followed the regulatory route is presented and its
      relevance to the slippery slope argument is considered. The arguments presented
      by both sides are critically assessed. The conclusion suggested is that evidence
      of harms to vulnerable individuals or to society, consequent upon legalization,
      is insufficient to support continued denial of freedom to those competent adults
      who seek physician assistance in hastening their death. 

PMID- 23856181
TI  - Identification of the likely translational start of Mycobacterium tuberculosis
      GyrB.
AB  - BACKGROUND: Bacterial DNA gyrase is a validated target for antibacterial
      chemotherapy. It consists of two subunits, GyrA and GyrB, which form an A2B2
      complex in the active enzyme. Sequence alignment of Mycobacterium tuberculosis
      GyrB with other bacterial GyrBs predicts the presence of 40 potential additional
      amino acids at the GyrB N-terminus. There are discrepancies between the M.
      tuberculosis GyrB sequences retrieved from different databases, including
      sequences annotated with or without the additional 40 amino acids. This has
      resulted in differences in the GyrB sequence numbering that has led to the
      reporting of previously known fluoroquinolone-resistance mutations as novel
      mutations. FINDINGS: We have expressed M. tuberculosis GyrB with and without the
      extra 40 amino acids in Escherichia coli and shown that both can be produced as
      soluble, active proteins. Supercoiling and other assays of the two proteins show
      no differences, suggesting that the additional 40 amino acids have no effect on
      the enzyme in vitro. RT-PCR analysis of M. tuberculosis mRNA shows that
      transcripts that could yield both the longer and shorter protein are present.
      However, promoter analysis showed that only the promoter elements leading to the
      shorter GyrB (lacking the additional 40 amino acids) had significant activity.
      CONCLUSION: We conclude that the most probable translational start codon for M.
      tuberculosis GyrB is GTG (Val) which results in translation of a protein of 674
      amino acids (74 kDa).

PMID- 23856182
TI  - [Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].
AB  - INTRODUCTION: A large percentage of patients with Parkinson's disease (PD)
      develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3
      to 5 years of starting dopaminergic therapy, and these motor complications are
      refractory to treatment. Several authors refer to this stage of the disease as
      advanced Parkinson's disease. OBJECTIVE: To define the clinical manifestations of
      advanced PD and the risk factors for reaching this stage of the disease.
      DEVELOPMENT: This consensus document has been prepared by using an exhaustive
      literature search and by discussion of the contents by an expert group on
      movement disorders of the Sociedad Espanola de Neurologia (Spanish Neurology
      Society), coordinated by two of the authors (JK and MRL). CONCLUSIONS: Severe
      motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa,
      and cognitive decline are the main signs in the clinical phenotype of advanced
      PD.

PMID- 23856183
TI  - Characterization of the response to ecdysteroid of a novel cuticle protein R&R
      gene in the honey bee, Apis cerana cerana.
AB  - Genes encoding cuticle proteins are helpful subjects to study the molecular
      mechanisms of insect molting and metamorphosis. In this study, we isolated and
      characterized a novel cuticle protein R&R gene, referred to as AccCPR1, from Apis
      cerana cerana. The open reading frame of AccCPR1 has a length of 573 nt and
      encodes a protein of 190 amino acids that contains a chitin binding region and is
      a typical cuticle R&R-2 protein. Five putative E74 binding sites and four BR-C
      binding sites were predicted in the 5'-flanking region, which suggests a
      potential function in molting and metamorphosis. RT-qPCR showed that AccCPR1
      transcript occurred as the ecdysteroid titer decreased after reaching a peak,
      which suggests AccCPR1 expression requires a "pulse" regimen of ecdysteroids.
      This hypothesis was tested using different experimental strategies. When larvae
      were reared with different concentrations of 20E in their diet, the ecdysteroid
      peak repressed AccCPR1 expression. Exposure of the thoracic integument of the
      pupae in vitro to different concentration of 20E repressed AccCPR1 expression,
      which recovered after the removal of 20E. These results suggest that AccCPR1 is a
      typical cuticle R&R-2 protein that plays an important role in development, and an
      ecdysteroid pulse is critical for high AccCPR1 gene expression. 

PMID- 23856184
TI  - Hexokinase regulation in the hepatopancreas and foot muscle of the anoxia
      tolerant marine mollusc, Littorina littorea.
AB  - Hexokinase from the hepatopancreas and foot muscle of Littorina littorea
      undergoes stable modification of its kinetic and structural properties in
      response to prolonged oxygen deprivation. In the hepatopancreas, a reduction in
      the Km glucose for hexokinase from the anoxic animal suggests a more active
      enzyme form during anoxia. Conversely, in the foot muscle, an increase in Km ATP
      and a decrease in Vmax for anoxic snail hexokinase were consistent with a less
      active enzyme form during anoxia. In either case, the molecular basis for the
      stable modification of hexokinase kinetics is reversible phosphorylation. The
      activation of endogenous PKC and AMPK increased the Km glucose for anoxic
      hepatopancreas hexokinase to a value that was similar to the control Km glucose.
      Alternatively, stimulation of endogenous PKA, PKG, and CamK for control foot
      muscle hexokinase increased the Km ATP to a value similar to that seen for the
      anoxic enzyme form. In both tissues, activation of endogenous phosphatases
      reversed the effects of protein kinases. Dephosphorylation and activation of
      hepatopancreas hexokinase during anoxia may allow for increased shunting of
      glucose-6-phosphate into the pentose phosphate pathway, thereby producing
      reducing equivalents of NADPH needed for antioxidant defense upon tissue re
      oxygenation. Conversely, phosphorylation and inhibition of foot muscle hexokinase
      during anoxia may reflect the decreased need for glucose oxidation during
      hypometabolism. 

PMID- 23856185
TI  - Olanzapine-induced changes in glucose metabolism are independent of the melanin
      concentrating hormone system.
AB  - Atypical antipsychotic drugs such as Olanzapine (Ola) induce weight gain and
      metabolic changes associated with the development of type 2 diabetes. The
      mechanisms underlying these undesired side-effects are currently unknown. Chagnon
      et al. showed that the common allele rs7973796 of the prepro-melanin
      concentrating hormone (PMCH) gene is associated with a greater body mass index in
      Ola-treated schizophrenic patients. As PMCH encodes for the orexigenic
      neuropeptide melanin-concentrating hormone (MCH), it was hypothesized that MCH is
      involved in Ola-induced metabolic changes. We have recently reported that the
      intragastric infusion of Ola results in hyperglycaemia and insulin resistance in
      male rats. In order to test in vivo the possible involvement of the PMCH gene in
      the pathogenesis of Ola side-effects, we administered Ola intragastrically in
      wild-type (WT) and PMCH knock-out (KO) rats. Our results show that glucose and
      corticosterone levels, as well as endogenous glucose production, are elevated by
      the infusion of Ola in both WT and KO animals. Thus, the lack of MCH does not
      seem to affect the acute effects of Ola on glucose metabolism. On the other hand,
      these effects might be obliterated by compensatory changes in other hypothalamic
      systems. In addition, possible modulatory effects of the MCH KO on the long term
      effects of Ola, i.e. increased adiposity, body weight gain, have not been
      investigated yet.

PMID- 23856187
TI  - The role of oxytocin in social bonding, stress regulation and mental health: an
      update on the moderating effects of context and interindividual differences.
AB  - In this review we summarize the results and conclusions of five studies as
      presented in a symposium at the 42nd annual meeting of the International Society
      for Psychoneuroendocrinology, in New York in September 2012. Oxytocin
      administration has received increasing attention for its role in promoting
      positive social behavior and stress regulation, and its potential as a
      therapeutic intervention for addressing various aspects of psychiatric disorders.
      However, it has been noted that the observed effects are not uniformly
      beneficial. In this paper we present five new studies each concluding that
      contextual and interindividual factors moderate the effects of oxytocin, as well
      as peripheral oxytocin levels. These findings are in accordance with the recent
      idea that oxytocin administration may increase sensitivity to social salience
      cues and that the interpretation of these cues may be influenced by contextual
      (i.e. presence of a stranger versus friend) or interindividual factors (i.e. sex,
      attachment style, or the presence of psychiatric symptoms). When social cues in
      the environment are interpreted as "safe" oxytocin may promote prosociality but
      when the social cues are interpreted as "unsafe" oxytocin may promote more
      defensive and, in effect, "anti-social" emotions and behaviors. Likewise,
      oxytocin appears to promote such agonistic tendencies in individuals who are
      chronically pre-disposed to view the social milieu in uncertain and/or in
      negative terms (e.g., those with borderline personality disorder, severe
      attachment anxiety and/or childhood maltreatment). In all, these studies in pre
      clinical animal, healthy humans and patients samples further reinforce the
      importance of considering both contextual and interindividual factors when trying
      to understand the role of oxytocin as a biological substrate underlying social
      bonding and stress regulatory processes and when studying the effects of oxytocin
      administration in particular in patients with (increased risk for) psychiatric
      disorders. 

PMID- 23856186
TI  - Associations among daily stressors and salivary cortisol: findings from the
      National Study of Daily Experiences.
AB  - While much research has focused on linking stressful experiences to emotional and
      biological reactions in laboratory settings, there is an emerging interest in
      extending these examinations to field studies of daily life. The current study
      examined day-to-day associations among naturally occurring daily stressors and
      salivary cortisol in a national sample of adults from the second wave of the
      National Study of Daily Experiences (NSDE). A sample of 1694 adults (age=57,
      range=33-84; 44% male) completed telephone interviews detailing their stressors
      and emotions on eight consecutive evenings. Participants also provided saliva
      samples upon waking, 30min post-waking, before lunch and before bed, on four
      consecutive interview days resulting in 5995 days of interview/cortisol data.
      Analyses revealed three main findings. First, cortisol AUC was significantly
      higher on stressor days compared to stressor-free days, particularly for
      arguments and overloads at home, suggesting that daily stressors are associated
      with increased cortisol output, but that not all daily stressors have such an
      influence. Second, individuals reporting a greater frequency of stressor days
      also exhibited a steeper diurnal cortisol slope. Finally, daily stressor-cortisol
      associations were unaltered after adjustment for daily negative affect and
      physical symptoms. Our discussion focuses on the influence of naturally occurring
      daily stressors on daily cortisol and the role of daily diary approaches for
      studying healthy cortisol responses to psychosocial stressors outside of
      traditional laboratory settings. 

PMID- 23856188
TI  - Recruitment in pediatric clinical research was influenced by study
      characteristics and pediatricians' perceptions: a multicenter survey.
AB  - OBJECTIVES: The aim of this survey was to quantify refusal rates and identify
      factors of refusal pertaining to studies and recruiting pediatricians in the
      research recruitment process. STUDY DESIGN AND SETTING: We performed a cross
      sectional survey on all clinical studies conducted in six pediatric Clinical
      Investigation Centers in France over an 18-month period. Data were retrieved
      using a data collection form for the characteristics of each of the studies
      included in the survey and a questionnaire addressed to recruiting pediatricians.
      Multilevel models were used for the statistical analysis. RESULTS: Overall, 145
      pediatricians approached the families of 999 children and adolescents for
      participation in 44 studies. In the 36 of the 44 studies that enrolled subjects,
      median refusal rate was 12.5% (Q1-Q3, 0-28%). Lower refusal rates were associated
      with therapeutic drug use as the focus of the study [odds ratio (OR), 0.51; 95%
      CI: 0.25, 1.05], additional hospital stays required for the study (OR, 0.53; 95%
      CI: 0.28, 0.99), longer duration of the inclusion visit (OR, 0.93/10 min; 95% CI:
      0.87, 1), and recruitment by a pediatrician with university teaching
      responsibilities (OR, 0.26; 95% CI: 0.10, 0.68). Refusal rate was higher when the
      recruiting pediatrician perceived the study as generating heavy practical burden
      for the subject and/or its family (OR, 1.3; 95% CI: 1.17, 1.45). CONCLUSION:
      Refusal to participate in clinical research was low and was influenced by factors
      associated to the objectives and conduct of the studies and factors related to
      the characteristics and perceptions of the recruiting pediatricians.

PMID- 23856189
TI  - A survey of patient's perceptions of what is "adverse" in manual physiotherapy
      and predicting who is likely to say so.
AB  - OBJECTIVES: The primary objective was to describe the patient perspective
      regarding the identification and occurrence of adverse responses related to
      manual therapy. A secondary objective evaluated predictors of the incidence rate
      of adverse responses identified by patients receiving manual physiotherapy. STUDY
      DESIGN AND SETTING: A cross-sectional survey of patients receiving manual
      physiotherapy recruited by physiotherapists in Canada was conducted. The survey
      included questions about the symptoms patients identified as adverse, causal
      associations with treatment, and the impact of contextual factors. Descriptive
      statistics are reported, and Poisson modeling predicted factors associated with
      identification of adverse responses. RESULTS: A response rate of 76.2% (324 of
      425) was obtained. Having lumbar spine dysfunction was a significant predictor of
      all adverse responses (incidence rate ratio [IRR] 95% confidence interval [CI] =
      1.513 [1.025, 2.235], P = 0.037) and was associated with 51% greater
      identification of adverse responses compared with those with an extremity
      disorder. Expectation of soreness was "protective" against identifying major
      adverse responses (IRR [95% CI] = 0.915 [0.838, 0.999], P = 0.047); they had an
      8.5% lower rate of identifying major adverse responses relative to those without
      this expectation. CONCLUSIONS: The patient perspective is important to consider
      if a comprehensive framework for defining adverse responses in manual therapies
      is to be developed.

PMID- 23856190
TI  - US Food and Drug Administration documents can provide unpublished evidence
      relevant to systematic reviews.
AB  - OBJECTIVES: A key systematic review (SR) methodology is comprehensive searching.
      The Drug Effectiveness Review Project (DERP) SRs search US Food and Drug
      Administration (FDA) documents to identify unpublished evidence. This study
      evaluates the success of those efforts. STUDY DESIGN AND SETTING: We examined
      DERP reports published since 2003 for the use of FDA preapproval and
      postmarketing documents. We categorized evidence as (1) unique unpublished
      studies, (2) supplemental unpublished data, or (3) FDA postmarketing data
      analysis. Three reviewers independently assigned predetermined impact categories
      (e.g., qualitative or quantitative usage, fills gaps, confirms findings, and
      alters conclusions), resolving disagreements through consensus. RESULTS: Among
      114 DERP reports, 19% included unpublished studies and/or supplemental data and
      10% included postmarketing analyses. From 175 preapproval documents, 14% provided
      eligible unpublished studies and 4.0% supplemental unpublished data that helped
      confirm previous findings, identify important harms, and fill gaps in knowledge
      about understudied subpopulations, outcomes, and comparisons. Report conclusion
      statements changed in 9 of 33 instances of premarketing documents compared with 4
      of 12 postmarketing analyses. CONCLUSIONS: The FDA documents can provide
      important unpublished evidence for SRs, although in a small proportion of cases.
      Future research should identify attributes that predict which reviews may benefit
      most from review of FDA documents.

PMID- 23856191
TI  - Topological and phylogenetic analyses of bacterial holin families and
      superfamilies.
AB  - Holins are small "hole-forming" transmembrane proteins that mediate bacterial
      cell lysis during programmed cell death or following phage infection. We have
      identified fifty two families of established or putative holins and have included
      representative members of these proteins in the Transporter Classification
      Database (TCDB; www.tcdb.org). We have identified the organismal sources of
      members of these families, calculated their average protein sizes, estimated
      their topologies and determined their relative family sizes. Topological analyses
      suggest that these proteins can have 1, 2, 3 or 4 transmembrane alpha-helical
      segments (TMSs), and members of a single family are frequently, but not always,
      of a single topology. In one case, proteins of a family proved to have either 2
      or 4 TMSs, and the latter arose by intragenic duplication of a primordial 2 TMS
      protein-encoding gene resembling the former. Using established statistical
      approaches, some of these families have been shown to be related by common
      descent. Seven superfamilies, including 21 of the 52 recognized families were
      identified. Conserved motif and Pfam analyses confirmed most superfamily
      assignments. These results serve to expand upon the scope of channel-forming
      bacterial holins. 

PMID- 23856192
TI  - Intracranially recorded interictal spikes: relation to seizure onset area and
      effect of medication and time of day.
AB  - OBJECTIVE: The relationship between seizures and interictal spikes remains
      undetermined. We analyzed intracranial EEG (icEEG) recordings to examine the
      relationship between the seizure onset area and interictal spikes. METHODS: 80
      unselected patients were placed into 5 temporal, 4 extratemporal, and one
      unlocalized groups based on the location of the seizure onset area. We studied 4
      h icEEG epochs, removed from seizures, from day-time and night-time during both
      on- and off-medication periods. Spikes were detected automatically from electrode
      contacts sampling the hemisphere ipsilateral to the seizure onset area. RESULTS:
      There was a widespread occurrence of spikes over the hemisphere ipsilateral to
      the seizure onset area. The spatial distributions of spike rates for the
      different patient groups were different (p<0.0001, chi-square test). The area
      with the highest spike rate coincided with the seizure onset area only in half of
      the patients. CONCLUSION: The spatial distribution of spike rates is strongly
      associated with the location of the seizure onset area, suggesting the presence
      of a distributed spike generation network, which is related to the seizure onset
      area. SIGNIFICANCE: The spatial distribution of spike rates, but not the area
      with the highest spike rate, may hold value for the localization of the seizure
      onset area.

PMID- 23856193
TI  - Simultaneous bicoherence analysis of occipital and frontal electroencephalograms
      in awake and anesthetized subjects.
AB  - OBJECTIVE: Occipital electroencephalogram (EEG) activity is known to be different
      from the frontal EEG during wakefulness and anesthesia. However, less is known
      about occipital non-linear dynamics analyzed by EEG-bicoherence, which can
      reflect the oscillatory features that are dependent on thalamocortical
      modulation. METHODS: Forty patients were anesthetized using sevoflurane (1% or
      3%) combined with remifentanil. Frontal and occipital EEGs were simultaneously
      collected, and bicoherence was analyzed before and after induction of anesthesia.
      RESULTS: Occipital awake EEGs often demonstrate a bicoherence alpha peak,
      differing from frontal awake EEGs in the absence of bicoherence growth. With 1%
      sevoflurane, occipital alpha bicoherence disappeared and frontal alpha
      bicoherence peaks appeared. Although 3% sevoflurane caused an increase in
      occipital delta-theta normalized power, similar to the frontal region (peak
      relative delta-theta power, 13.1 +/- 2.2% vs. 12.2 +/- 2.7%, p>0.05), occipital
      bicoherence showed no growth in any frequency area, contrasting with the frontal
      bicoherence spectrum with a conspicuous peak in the delta-theta area (19.8 +/-
      8.9 vs. 43.6 +/- 13.8, p<0.05). CONCLUSIONS: The occipital bicoherence spectrum
      in the peri-anesthesia period is quite different from the frontal bicoherence
      spectrum, which is not usually obvious in the power spectrum. SIGNIFICANCE:
      Nonlinear regulation of the occipital EEG is different from the frontal EEG
      during every stage of anesthesia.

PMID- 23856194
TI  - Quercetin suppresses inflammation by reducing ERK1/2 phosphorylation and NF kappa
      B activation in Leptin-induced Human Umbilical Vein Endothelial Cells (HUVECs).
AB  - BACKGROUND: High concentrations of plasma leptin and the release of pro
      inflammatory cytokines in leptin-resistance in obesity have been reported to
      trigger endothelial dysfunction. The objective of this study was to elucidate the
      role of quercetin in modulating leptin-induced inflammation as assessed by the
      levels of Ob-Ra expression, ERK1/2 phosphorylation, NF-kappa B activation and TNF
      alpha secretion in umbilical vein endothelial cells (HUVECs) in vitro. FINDINGS:
      HUVECs were exposed to either control levels (0 ng/ml) or 500 ng/mL leptin (L)
      for 48 hours, followed by control or 125 uM quercetin (Q) for another 6 h. The
      experimental groups were as follows: L0Q0, L0Q125, L500Q0, L500Q125. The presence
      of the short chain leptin receptor isoform Ob-Ra in HUVECs was determined by
      Western blot and immunocytochemistry analyses. Ob-Ra expression, ERK1/2
      phosphorylation, NF-kappa B activation and TNF-alpha secretion were quantified by
      ELISA, and NF-kappa B activationby immunofluorescence staining. Our results
      showed that Ob-Ra expression, ERK1/2 phosphorylation and NF-kappa B activation
      increased significantly after 500 ng/mL leptin exposure (1.8x, 1.5x, 6.2x for Ob
      Ra, ERK1/2 and NF-kappa B, respectively), but were reduced by addition of 125 uM
      quercetin (0.7x, 0.3x and 0.4x for Ob-Ra, ERK1/2 and NF-kappa B, respectively),
      and that quercetin could also partially suppress leptin-induced TNF-alpha
      secretion (3.8x) by 0.8x. CONCLUSION: Exposure of HUVECs to leptin up-regulated
      Ob-Ra expression and elevated ERK1/2 phosphorylation and NFkB activation, and
      increased TNF-alpha secretion. These effects strongly suppressed by quercetin,
      with the exception of TNF-alpha which was partially suppressed. The findings
      might be of clinical significance, as endothelial dysfunction that could lead to
      cardiovascular disease is preventable, and quercetin is a natural compound found
      in various plants and fruits.

PMID- 23856195
TI  - The microsporidian Enterocytozoon hepatopenaei is not the cause of white feces
      syndrome in whiteleg shrimp Penaeus (Litopenaeus) vannamei.
AB  - BACKGROUND: The microsporidian Enterocytozoon hepatopenaei was first described
      from Thailand in 2009 in farmed, indigenous giant tiger shrimp Penaeus (Penaeus)
      monodon. The natural reservoir for the parasite is still unknown. More recently,
      a microsporidian closely resembling it in morphology and tissue preference was
      found in Thai-farmed, exotic, whiteleg shrimp Penaeus (Litopenaeus) vannamei
      exhibiting white feces syndrome (WFS). Our objective was to compare the newly
      found pathogen with E. hepatopenaei and to determine its causal relationship with
      WFS. RESULTS: Generic primers used to amplify a fragment of the small subunit
      ribosomal RNA (ssu rRNA) gene for cloning and sequencing revealed that the new
      parasite from WFS ponds had 99% sequence identity to that of E. hepatopenaei,
      suggesting it was conspecific. Normal histological analysis using tissue sections
      stained with hematoxylin and eosin (H&E) revealed that relatively few tubule
      epithelial cells exhibited spores, suggesting that the infections were light.
      However, the H&E results were deceptive since nested PCR and in situ
      hybridization analysis based on the cloned ssu rRNA gene fragment revealed very
      heavy infections in tubule epithelial cells in the central region of the
      hepatopancreas in the absence of spores. Despite these results, high prevalence
      of E. hepatopenaei in shrimp from ponds not exhibiting WFS and a pond that had
      recovered from WFS indicated no direct causal association between these
      infections and WFS. This was supported by laboratory oral challenge trials that
      revealed direct horizontal transmission to uninfected shrimp but no signs of WFS.
      CONCLUSIONS: The microsporidian newly found in P. vannamei is conspecific with
      previously described E. hepatopenaei and it is not causally associated with WFS.
      However, the deceptive severity of infections (much greater than previously
      reported in P. monodon) would undoubtedly have a negative effect on whiteleg
      shrimp growth and production efficiency and this could be exacerbated by the
      possibility of horizontal transmission revealed by laboratory challenge tests.
      Thus, it is recommended that the PCR and in situ hybridization methods developed
      herein be used to identify the natural reservoir species so they can be
      eliminated from the shrimp rearing system.

PMID- 23856196
TI  - Intramyocardial thrombin promotes angiogenesis and improves cardiac function in
      an experimental rabbit model of acute myocardial infarction.
AB  - OBJECTIVE: Thrombin has been reported to play a pivotal role in the initiation of
      angiogenesis by indirectly regulating and organizing a network of angiogenic
      molecules. On the basis of these reports, we investigated the angiogenic action
      of thrombin in a rabbit model of acute myocardial infarction. METHODS: A rabbit
      model of acute myocardial infarction was established by ligation of the left
      anterior descending coronary branch. Subjects were then divided into 2 groups and
      treated with intramyocardial administration of thrombin (2500 IU; n = 13) or an
      equal volume of normal saline (n = 13). Four weeks later, animals were euthanized
      and histopathologic analysis, immunohistochemical staining for endothelial
      markers CD31 and vascular endothelial growth factor-A, and electron microscopy
      examination were performed on excised hearts. Electrocardiography, cardiac
      enzymes, and assessment of cardiac function by measuring left ventricular end
      diastolic pressure and ejection fraction were recorded before and after
      myocardial infarction, and both left ventricular end-diastolic pressure and
      ejection fraction were further measured on the day of euthanasia (n = 5-8 in each
      case). RESULTS: Increased levels of troponin, ST elevation, and
      histopathologically confirmed myocardial infarction were observed in all animals.
      A significant increase of microvessel density at the infarct border zone, as
      evaluated by CD31 immunohistochemistry, was observed in the thrombin-treated
      group compared with the control group (30.3 +/- 12.8 vs 12.6 +/- 4.8, P = .0065).
      A significantly higher number of vascular endothelial growth factor-A-positive
      vessels at the infarct border zone was observed in the thrombin-treated animals
      compared with the control group (21.8 +/- 8.9 vs 5.6 +/- 4.4; P = .0009). The
      thrombin-treated animals showed a statistically significant reduction in left
      ventricular end-diastolic pressure values (6.9 +/- 1.8 mm Hg vs 12.7 +/- 2.2 mm
      Hg, P = .0002) and significant improvement in left ventricular ejection fraction
      (59.8% +/- 3.1% vs 42.2% +/- 6.14%, P = .002) on the day of euthanasia compared
      with the post-infarct day, reflecting significantly improved cardiac function
      compared with control subjects that showed no significant change. CONCLUSIONS:
      Intramyocardial administration of thrombin seems to promote angiogenesis and
      improve cardiac function of the ischemic myocardium, which may provide a new
      therapeutic approach in patients with myocardial ischemia.

PMID- 23856197
TI  - Discussion.

PMID- 23856198
TI  - Management of dilated ascending aorta during aortic valve replacement: valve
      replacement alone versus aorta wrapping versus aorta replacement.
AB  - OBJECTIVES: The optimal management of dilated ascending aorta during aortic valve
      replacement (AVR) remains controversial. This study compared the outcomes among 3
      different managements (AVR alone, aorta wrapping, and aorta replacement) for the
      dilated ascending aorta. METHODS: The study enrolled 499 consecutive non-Marfan
      patients undergoing AVR in the presence of the ascending aorta dilatation (40 to
      55 mm). We evaluated rates of death and aortic events; in addition, we evaluated
      the aortic expansion rate by serial echocardiography. RESULTS: The surgery
      involved AVR alone (n = 362), aorta wrapping (n = 67), or aorta replacement (n =
      70). Early mortality occurred in 1.2% (n = 6, P = .61). Throughout 1590.0 patient
      years of follow-up, 47 deaths occurred. The 5-year survival rates were 90.1% +/-
      2.0%, 91.8% +/- 3.5%, and 82.2% +/- 7.5% in the AVR alone, aorta wrapping, and
      aorta replacement groups, respectively (P = .64). One aortic event (acute type A
      dissection) occurred in the AVR alone group. For the AVR alone group, the median
      aortic expansion rate was -0.6 mm/y (interquartile range, -3.2 to 0.6 mm/y). The
      aortic expansion rates were affected neither by the morphology of aortic valves
      (bicuspid vs tricuspid; P = .10) nor by the initial aorta diameter (gamma = 
      0.31, P = .61). Clinically relevant aortic expansion (>=5 mm/y) was observed only
      in 5 patients; of these patients, 2 showed the aortic diameter of 60 mm or
      greater at the end of follow-up. CONCLUSIONS: Compared with concomitant aortic
      wrapping or replacement, AVR alone achieved similar clinical outcomes, showing
      considerably low risks of adverse aortic events or relevant aortic expansion in
      dilated ascending aorta. These findings argue against routine aortic replacement
      at the time of AVR.

PMID- 23856199
TI  - Surgical risk algorithm as a measure of successful adoption of transapical
      transcatheter aortic valve implantation.
AB  - OBJECTIVE: This study was performed to assess the Society of Thoracic Surgeons
      (STS) score as a measure of successful adoption of transapical transcatheter
      aortic valve implantation (TAVI). METHODS: The STS score for estimated surgical
      mortality was calculated and used to select the first 140 consecutive patients
      undergoing transapical TAVI. The STS score also was used to estimate
      postoperative morbidity. The comparisons were made between the observed and
      estimated mortality and morbidity in the entire group, as well as in the first
      35, second 35, and last 70 consecutive patients. RESULTS: The differences in
      outcomes between the first 35, second 35, and last 70 patients were statistically
      significant for surgical mortality (20.0% vs 14.3% vs 2.9%; P = .045), composite
      morbidity/mortality (34.3% vs 40.1% vs 15.7%; P = .020), and long length of stay
      (34.3% vs 45.7% vs 18.6%; P = .027). There were trends of marked decreases in
      prolonged ventilation (11.4% vs 20.0% vs 4.3%; P = .061), and acute renal failure
      (14.3% vs 20.0% vs 4.3%; P = .059). In the first 70 patients there were no
      significant differences between observed and STS estimated incidences in
      mortality and composite mortality/major morbidity. In the latter 70 patients the
      observed incidences were lower than STS predicted values in mortality (2.9% vs
      9.6%; P = .056), composite major morbidity/mortality (15.7% vs 33.8%; P = .001),
      and prolonged ventilation (4.3% vs 25.1%; P < .0001). CONCLUSIONS: Only after a
      protracted learning curve did the anticipated benefits of transapical TAVI
      materialize for patients at high risk for surgery as predicted by the STS risk
      algorithms.

PMID- 23856200
TI  - Endoscopic lung abscess drainage with argon plasma coagulation.

PMID- 23856201
TI  - Effect of systematic downsizing rigid ring annuloplasty in patients with moderate
      ischemic mitral regurgitation.
AB  - OBJECTIVE: Functional ischemic mitral regurgitation (FIMR) increases mortality
      independently of the baseline characteristics and ventricular function. The
      effect of treating FIMR with annuloplasty is unclear when mitral regurgitation is
      moderate. Myocardial revascularization alone has been shown to improve mitral
      valve function. METHODS: We randomized 31 patients with moderate (grade 2-4) FIMR
      to receive either coronary artery bypass grafting (CABG) alone or CABG plus
      downsizing mitral ring annuloplasty. The patients were followed up for clinical
      outcomes and echocardiographic assessment of mitral valve function and left
      ventricular dimensions at 3 and 12 months. Clinical improvement was assessed
      using the Minnesota quality-of-life questionnaire, 6-minute walk test, and brain
      natriuretic peptide levels. RESULTS: The clinical course was similar in the 2
      groups of patients during the study period. FIMR was perfectly corrected
      intraoperatively in the ring group. Echocardiographic follow-up at 3 months
      showed no difference in the FIMR grade between the 2 groups (66% less than grade
      2 in the CABG alone and 86% in the CABG plus ring group; P = .316). The
      improvement in the CABG alone group was even more marked at 12 months (85% less
      than grade 2 in the CABG group and 85% in the CABG plus ring group). The left
      ventricular ejection fraction was significantly better at 3 months in the CABG
      alone group, although at 12 months, the left ventricular ejection fraction in the
      2 groups had improved similarly. CONCLUSIONS: Although initially effective at
      reducing moderate FIMR, the addition of a ring did not change the clinical course
      after CABG surgery. At 12 months, no echocardiographic difference was found in
      terms of residual mitral regurgitation, left ventricular dimensions and function,
      or clinical outcomes.

PMID- 23856203
TI  - A novel surgical marking system for small peripheral lung nodules based on radio
      frequency identification technology: Feasibility study in a canine model.
AB  - OBJECTIVE: We investigated the feasibility and accuracy of a novel surgical
      marking system based on radiofrequency identification (RFID) technology for the
      localization of small peripheral lung nodules (SPLNs) in a canine model. METHODS:
      The system consists of 4 components: (1) micro RFID tags (13.56 MHz, 1.0 * 1.0 *
      0.8 mm), (2) a tag delivery system with a bronchoscope, (3) a wand-shaped
      locating probe (10-mm diameter), and (4) a signal processing unit with audio
      interface. Before the operation, pseudolesions mimicking SPLNs were prepared in 7
      dogs by injecting colored collagen. By use of a computed tomographic (CT) guide,
      an RFID tag was placed via a bronchoscope close to each target lesion. This was
      then followed by scanning with the locating probe, and wedge resection was
      performed when possible. Operators can locate the tag by following the sound
      emitted by the system, which exhibits tone changes according to the tag-probe
      distance. The primary outcome measure was the rate of wedge resection with good
      margins. RESULTS: A total of 10 pseudolesions imitating SPLNs were selected as
      targets. During thoracoscopic procedures, 9 of 10 tags were detected by the
      system within a median of 27 seconds. Wedge resections were performed for these 9
      lesions with a median margin of 11 mm. The single failure was caused by tag
      dislocation to the central airway. CONCLUSIONS: Successful localization and wedge
      resection of pseudolesions with appropriate margins were accomplished in an
      experimental setting. Our RFID marking system has future applications for
      accurately locating SPLNs in a clinical setting.

PMID- 23856204
TI  - Local recurrence after surgery for non-small cell lung cancer: a recursive
      partitioning analysis of multi-institutional data.
AB  - OBJECTIVE: To define subgroups at high risk of local recurrence (LR) after
      surgery for non-small cell lung cancer using a recursive partitioning analysis
      (RPA). METHODS: This Institutional Review Board-approved study included patients
      who underwent upfront surgery for I-IIIA non-small cell lung cancer at Duke
      Cancer Institute (primary set) or at other participating institutions (validation
      set). The 2 data sets were analyzed separately and identically. Disease
      recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was
      considered an LR. Recursive partitioning was used to build regression trees for
      the prediction of local recurrence-free survival (LRFS) from standard clinical
      and pathological factors. LRFS distributions were estimated with the Kaplan-Meier
      method. RESULTS: The 1411 patients in the primary set had a 5-year LRFS rate of
      77% (95% confidence interval [CI], 0.74-0.81), and the 889 patients in the
      validation set had a 5-year LRFS rate of 76% (95% CI, 0.72-0.80). The RPA of the
      primary data set identified 3 terminal nodes based on stage and histology. These
      nodes and their 5-year LRFS rates were as follows: (1) stage I/adenocarcinoma,
      87% (95% CI, 0.83-0.90); (2) stage I/squamous or large cell, 72% (95% CI, 0.65
      0.79); and (3) stage II-IIIA, 62% (95% CI, 0.55-0.69). The validation RPA
      identified 3 terminal nodes based on lymphovascular invasion (LVI) and stage: (1)
      no LVI/stage IA, 82% (95% CI, 0.76-0.88); (2) no LVI/stage IB-IIIA, 73% (95% CI,
      0.69-0.80); and (3) LVI, 58% (95% CI, 0.47-0.69). CONCLUSIONS: The risk of LR was
      similar in the primary and validation patient data sets. There was discordance
      between the 2 data sets regarding the clinical factors that best segregate
      patients into risk groups.

PMID- 23856205
TI  - Chest wall reconstruction after resection of a chest wall sarcoma by
      osteosynthesis with the titanium MatrixRIB (Synthes) system.

PMID- 23856206
TI  - Transapical aortic valve (JenaValve) implantation for severe aortic insufficiency
      and aortic aneurysm.

PMID- 23856202
TI  - Different impact of sex on baseline characteristics and major periprocedural
      outcomes of transcatheter and surgical aortic valve interventions: Results of the
      multicenter Italian OBSERVANT Registry.
AB  - BACKGROUND: Despite the widespread use of transcatheter aortic valve implantation
      (TAVI), the role of sex on outcome after TAVI or surgical aortic valve
      replacement (AVR) has been poorly investigated. We investigated the impact of sex
      on outcome after TAVI or AVR. METHODS: There were 2108 patients undergoing TAVI
      or AVR who were enrolled in the Italian Observational Multicenter Registry
      (OBSERVANT). Thirty-day mortality, major periprocedural morbidity, and
      transprosthetic gradients were stratified by sex according to interventions.
      RESULTS: Female AVR patients showed a worse risk profile compared with male AVR
      patients, given the higher mean age, prevalence of frailty score of 2 or higher,
      New York Heart Association class of 3 or higher, lower body weight, and
      preoperative hemoglobin level (P <= .02). Similarly, female TAVI patients had a
      different risk profile than male TAVI patients, given a higher age and a lower
      body weight and preoperative hemoglobin level (P <= .005), but with a similar New
      York Heart Association class, frailty score, EuroSCORE (P = NS), a better left
      ventricular ejection fraction and a lower prevalence of left ventricular ejection
      fraction less than 30%, porcelain aorta, renal dysfunction, chronic obstructive
      pulmonary disease, arteriopathy, and previous cardiovascular surgery or
      percutaneous coronary intervention (P <= .01). Women showed a smaller aortic
      annulus than men in both populations (P < .001). Female sex was an independent
      predictor in the AVR population for risk-adjusted 30-day mortality (odds ratio
      [OR], 2.34; P = .043) and transfusions (OR, 1.47; P = .003), but not for risk
      adjusted acute myocardial infarction, stroke, vascular complications, permanent
      atrioventricular block (P = NS). Female sex was an independent predictor in the
      TAVI population for risk-adjusted major vascular complications (OR, 2.92; P =
      .018) and transfusions (OR, 1.93; P = .003), but proved protective against
      moderate to severe postprocedural aortic insufficiency (P = .018). CONCLUSIONS:
      Female sex is a risk factor for mortality after aortic valve replacement, for
      major vascular complications after TAVI, and for transfusions after both
      approaches.

PMID- 23856207
TI  - Radiologic evaluation for volume and weight of remnant lung in living lung
      donors.
AB  - OBJECTIVE: Living-lung donors lose pulmonary function of a right or left lower
      lobe in exchange for a noble donation; however, Chen and colleagues reported
      postoperative pulmonary function of the donors was significantly better than the
      estimated values. The purpose of this study was to investigate if the improvement
      of postoperative pulmonary function is associated with hypertrophic phenomena of
      remnant lung. METHODS: A total of 35 patients who underwent a right or left lower
      lobectomy for living-donor lobar lung transplantation in Kyoto University
      Hospital from 2008 to 2011 were evaluated by means of spirometry (forced vital
      capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon
      monoxide), and computed tomography scans both before and 1 year after the
      surgery. Postoperative predictions of pulmonary function and radiologic
      parameters were made based on the number of resected segments. The average
      radiologic density of the lung was determined as follows: (mean computed
      tomography number + 1000)/1000, and weight of the lung was calculated as follows:
      lung volume (mL) * average radiologic lung density (g/mL). The radiologic
      analysis was performed on both the surgical and contralateral sides. RESULTS:
      Postoperative forced vital capacity, forced expiratory volume in 1 second, and
      diffusing capacity for carbon monoxide were significantly higher than estimated
      values by 17.3% +/- 10.2% (P < .0001), 14.7% +/- 10.2% (P < .0001), and 10.9% +/-
      16. % (P < .002), respectively. Postoperative lung volume and weight of the
      surgical side were significantly higher than estimated values by 54.4% +/- 30.4%
      (P < .0001) and 28.1% +/- 15.7% (P < .0001), respectively. On the contralateral
      side, the postoperative lung volume was significantly higher than the estimated
      value by 12.6% +/- 15.3% (P < .0001), but postoperative weight was comparable
      with the estimated value (-2.3% +/- 8.8%; P = .07). CONCLUSIONS: Hypertrophic
      change of the ipsilateral remnant lung may be recognized in living lung donors.

PMID- 23856208
TI  - Single-institution, 22-year follow-up of 786 CarboMedics mechanical valves used
      for both primary surgery and reoperation.
AB  - OBJECTIVES: The long-term (>20 years) results for CarboMedics mechanical valves
      (Sorin Group, Milano, Italy) used for both primary surgery and reoperation have
      never been reported or compared. METHODS: Since 1990, a total of 787 CarboMedics
      valves have been implanted in 694 patients for aortic valve replacement,
      including 19 redo cases in 220 patients; for mitral valve replacement, including
      108 redo cases in 381 patents; and for double (aortic and mitral) valve
      replacement, including 29 redo cases in 93 patients. The follow-up data were
      complete for 7201 patient-years in 99.3% of the patients. RESULTS: The hospital
      mortality rate of the aortic, mitral, and double valve replacement groups was
      0.9%, 3.7%, and 4.3%, respectively. The corresponding freedom from valve-related
      morbidity rates in each group were 66.0%, 40.6%, and 48.0% at 20 years (P =
      .0206). A higher incidence of paravalvular leakage was observed in the mitral and
      double valve replacement groups than in the aortic valve replacement group (P =
      .0019). Of the cases of mitral paravalvular leakage after single mitral valve
      replacement, 97% occurred after redo single mitral valve replacement; 73% of the
      cases of mitral paravalvular leakage after double valve replacement occurred
      after redo double valve replacement. CONCLUSIONS: CarboMedics mechanical valves
      used for both primary surgery and reoperation for aortic, mitral, and double
      valve replacement can achieve satisfactory early and long-term results, even 20
      years after surgery. Care should be taken, however, to prevent paravalvular
      leakage in the mitral position during reoperation.

PMID- 23856209
TI  - Echocardiographic assessment of mitral durability in the late period following
      mitral valve repair: minithoracotomy versus conventional sternotomy.
AB  - OBJECTIVE: To compare the long-term echocardiographic mitral valve (MV)
      durability after MV repair performed through a minithoracotomy versus
      conventional sternotomy. METHODS: A total of 299 patients who underwent MV repair
      for degenerative mitral regurgitation (MR) through minithoracotomy (n = 179) or
      sternotomy (n = 120), between April 2004 and January 2010, were evaluated. To
      adjust the differences in baseline characteristics between the 2 groups, weighted
      Cox proportional-hazards regression models and inverse-probability-of-treatment
      weighting were used. RESULTS: There were no 30-day deaths in both groups and no
      significant differences in early complication rates. Clinical follow-up was
      complete in 294 patients (98.3%), with a median follow-up of 55.4 months
      (interquartile range, 34.4-66.9 months), during which there were 10 late deaths,
      2 strokes, and 3 reoperations for recurrent MR. After adjustment, the
      minithoracotomy group had similar risks for major adverse cardiac events (hazard
      ratio, 0.77; 95% confidence interval, 0.22-2.68; P = .68). Echocardiographic
      evaluation in the late period (>6 months) was possible in 292 patients (97.7%),
      with a median follow-up of 29.4 months (interquartile range, 13.3-49.7 months),
      during which 21 patients (12 in the minithoracotomy group and 9 in the sternotomy
      group) experienced significant MR (>2+). Freedom from significant MR at 5 years
      was 86.1% +/- 4.8% versus 85.3% +/- 5.5% (P = .63). After adjustment, the
      minithoracotomy group had similar risks for significant MR (hazard ratio, 0.81;
      95% confidence interval, 0.31-2.14; P = .67). CONCLUSIONS: A minithoracotomy
      approach for MV repair showed comparable clinical outcomes and efficacy to
      conventional sternotomy for MV repair.

PMID- 23856210
TI  - Utilizing commercial microwave for rapid and effective immunostaining.
AB  - There is an accumulating literature demonstrating the application of microwaves
      across a wide spectrum of histological techniques. Although exposure to
      microwaves for short periods resulted in substantial acceleration of all
      procedures this technique still is not adopted widely. In part, this may be due
      to concerns over solutions that will avoid induction of thermal damage to the
      tissue when using standard microwave. Here, we offer a cooling setup that can be
      used with conventional microwave ovens. We utilized dry ice for effective cooling
      during microwave irradiation of tissue samples. To prevent overheating, the cups
      with tissue during exposure to microwaves were surrounded with powdered dry ice.
      Since the dry ice does not touch the walls of the cups, freezing is prevented.
      Overheating is avoided by alternating the microwave treatment with 1-2 min time
      periods when the cups are cooled outside of the microwave oven. This technique
      was used on mouse brain sections that were immunostained with microglia-specific
      CD68 antiserum and astrocyte labeling GFAP antibody. Both standard and microwave
      assisted immonolabeling gave comparable results visualizing cells with fine
      processes and low background signal. Short incubation time in the microwave
      requires high concentrations of antibody for tissue immunostaining. We show that
      by prolonging the microwaving procedure we were able to reduce the antibody
      concentration to the levels used in standard immunostaining protocol. In summary,
      our technique gives a possibility to use a conventional microwave for rapid and
      effective immunolabeling resulting in reduced amount of antibody required for
      satisfactory immunostaining.

PMID- 23856211
TI  - Efficient sequential Bayesian inference method for real-time detection and
      sorting of overlapped neural spikes.
AB  - Overlapping of extracellularly recorded neural spike waveforms causes the
      original spike waveforms to become hidden and merged, confounding the real-time
      detection and sorting of these spikes. Methods proposed for solving this problem
      include using a multi-trode or placing a restriction on the complexity of
      overlaps. In this paper, we propose a rapid sequential method for the robust
      detection and sorting of arbitrarily overlapped spikes recorded with arbitrary
      types of electrodes. In our method, the probabilities of possible spike trains,
      including those that are overlapping, are evaluated by sequential Bayesian
      inference based on probabilistic models of spike-train generation and
      extracellular voltage recording. To reduce the high computational cost inherent
      in an exhaustive evaluation, candidates with low probabilities are considered as
      impossible candidates and are abolished at each sampling time to limit the number
      of candidates in the next evaluation. In addition, the data from a few subsequent
      sampling times are considered and used to calculate the "look-ahead probability",
      resulting in improved calculation efficiency due to a more rapid elimination of
      candidates. These sufficiently reduce computational time to enable real-time
      calculation without impairing performance. We assessed the performance of our
      method using simulated neural signals and actual neural signals recorded in
      primary cortical neurons cultured on a multi-electrode array. Our results
      demonstrated that our computational method could be applied in real-time with a
      delay of less than 10 ms. The estimation accuracy was higher than that of a
      conventional spike sorting method, particularly for signals with multiple
      overlapping spikes.

PMID- 23856212
TI  - Increased anesthesia time using 2,2,2-tribromoethanol-chloral hydrate with low
      impact on mouse psychoacoustics.
AB  - BACKGROUND: To examine psychoacoustics in mice, we have used 2,2,2
      tribromoethanol anesthesia in multiple studies. We find this drug is fast-acting
      and yields consistent results, providing 25-30 min of anesthesia. Our recent
      studies in binaural hearing prompted development of a regimen to anesthesia time
      to 1h. We tested a novel cocktail using 2,2,2-tribromoethanol coupled with low
      dose chloral hydrate to extend the effective anesthesia time. NEW METHOD: We have
      established an intraperitoneal dosing regimen for 2,2,2-tribromoethanol-chloral
      hydrate anesthesia. To measure efficacy of the drug cocktail, we measured
      auditory brainstem responses (ABRs) at 10 min intervals to determine the effects
      on hearing thresholds and wave amplitudes and latencies. RESULTS: This novel drug
      combination increases effective anesthesia to 1h. ABR Wave I amplitudes, but not
      latencies, are marginally suppressed. Additionally, amplitudes of the centrally
      derived Waves III and V show significant inter-animal variability that is
      independent of stimulus intensity. These data argue against the systematic
      suppression of ABRs by the drug cocktail. COMPARISON WITH EXISTING METHODS: Using
      2,2,2-tribromoethanol-chloral hydrate combination in psychoacoustic studies has
      several advantages over other drug cocktails, the most important being
      preservation of latencies from centrally- and peripherally-derived ABR waves. In
      addition, hearing thresholds are unchanged and wave amplitudes are not
      systematically suppressed, although they exhibit greater variability.
      CONCLUSIONS: We demonstrate that 375 mg/kg 2,2,2-tribromoethanol followed after 5
      min by 200mg/kg chloral hydrate provides an anesthesia time of 60 min, has
      negligible effects on ABR wave latencies and thresholds and non-systematic
      effects on amplitudes.

PMID- 23856213
TI  - Impact of nutritional state on lung transplant outcomes: the weight of the
      evidence.
AB  - Despite advances in perioperative and post-operative management, lung transplant
      recipients with select pre transplant risk factors have been shown to experience
      worse post-transplant outcomes in comparison to those without such risk factors.
      Among these variables, previous studies have shown that select markers of poor
      nutritional status prior to transplant, such as low body mass index (BMI) and
      hypoalbuminemia, have been associated with increased post-transplant mortality.
      In a past issue of the journal, Chamogeorgakis el al. examine a comprehensive
      battery markers previously associated with malnutrition to determine their impact
      on outcomes after lung transplantation. The authors find that hypoalbuminemia is
      associated with worse survival, but does not appear to affect the risk of post
      transplant infections. This article reviews the study presented by Chamogeorgakis
      et al. to discuss how it furthers our understanding of the impact of nutritional
      status on transplant-related outcomes and consider areas for future
      investigation. 

PMID- 23856214
TI  - Pathologic classification of antibody-mediated rejection correlates with donor
      specific antibodies and endothelial cell activation.
AB  - BACKGROUND: Humoral immune responses during heart transplantation may result in
      antibody-mediated rejection (AMR), which is now taken into account on
      endomyocardial biopsy (EMB) specimens and ranked according to the pathologic AMR
      (pAMR) grades of the International Society for Heart and Lung Transplantation
      classification. This classification might benefit from new immunohistological
      markers and validation by others biomarkers, namely donor-specific antibodies
      (DSA). METHODS: From the 293 protocol EMBs performed in 113 patients in our
      institution during a 1-year period for this prospective study, 280 EMB specimens
      were available with both histology and immunohistochemistry. C4d and labeling of
      intravascular cells by cluster of differentiation (CD) 68 were performed on
      paraffin sections. Available sera (n = 150) concomitant of EMB specimens were
      tested for the presence of DSA. All of the pAMR+ EMB specimens, along with a set
      of randomized pAMR0 EMB specimens, were immunolabeled for mammalian target of
      rapamycin (mTOR) effectors, phosphorylated 70 S6-kinase (p70S6K) and
      phosphorylated S6 ribosomal protein (pS6RP). RESULTS: AMR was diagnosed in 37 EMB
      specimens (13.2%): 1 pAMR1(I+), 27 pAMR1(H+), and 9 pAMR2. The proportion of DSA
      positive EMB varied according to the pAMR grade, with pAMR0, pAMR1(H+), and pAMR2
      EMB presenting 17.6%, 77.3%, and 100% of DSA-positivity, respectively. Among the
      30 pAMR+ specimens with available DSA testing and the 30 pAMR0 randomized
      specimens, mTOR pathway immunohistochemistry showed endothelial cell positivity
      for p70S6K in 17 pAMR+ EMB specimens (56.7%) and in 1 pAMR0 EMB specimen (3.3%).
      pS6RP was detected in 8 pAMR+ EMB specimens (26.7%) and in 1 pAMR0 EMB specimen
      (3.3%). CONCLUSIONS: p70S6K and pS6RP immunohistochemistry afford new markers of
      AMR on EMB specimens because their expression is correlated with microcirculation
      inflammation and DSA. The correlation of DSA with pAMR grade suggests that this
      grading system is valid.

PMID- 23856215
TI  - Attenuation of cardiac allograft vasculopathy by sirolimus: Relationship to time
      interval after heart transplantation.
AB  - BACKGROUND: The aim of the study was to assess temporal changes in plaque size
      and components after heart transplantation (HTx), and to evaluate the differences
      in treatment effects on plaque progression between sirolimus and calcineurin
      inhibitors (CNIs). METHODS: The study comprised 146 HTx recipients who were
      converted from CNIs to sirolimus as primary immunosuppressant (sirolimus group, n
      = 61) and those who were maintained on CNIs (CNI group, n = 85). A retrospective
      compositional analysis of serial virtual histology-intravascular ultrasound was
      performed. RESULTS: During a median follow-up of 2.8 years, there was a
      significant difference in plaque volume in favor of sirolimus between groups (p =
      0.004). When subjects were sub-classified according to the time interval between
      HTx and study inclusion, those in the early group (<=2 years after HTx) had a
      greater increase in plaque volume (p = 0.006), characterized by a higher
      progression rate of fibrous plaque volume (p = 0.01). The treatment difference
      between groups in plaque volume was identified in the early group in favor of
      sirolimus with attenuating effects on the progression of fibrous plaque component
      (both p = 0.03 for interaction). By contrast, there were significant differences
      in necrotic core and dense calcium volume (both p < 0.05 for interaction) in
      favor of CNIs in the late group (>=6 years after HTx). CONCLUSIONS: Compared with
      continued CNI therapy, sirolimus attenuated plaque progression in recipients with
      early conversion, but contributed to increases in necrotic core and dense calcium
      volume in those with late conversion. Our study supports the hypothesis that
      early initiation of sirolimus offers greater benefits in the treatment of CAV.

PMID- 23856216
TI  - Increased right-to-left ventricle diameter ratio is a strong predictor of right
      ventricular failure after left ventricular assist device.
AB  - BACKGROUND: Predictors of right ventricular failure (RVF) in patients with left
      ventricular assist devices (LVADs) have not been fully elucidated and are
      comprised mostly of clinical variables. We evaluated echocardiographic parameters
      associated with adverse outcomes in this population. METHODS: Transthoracic
      echocardiograms (TTEs) before continuous-flow LVAD implantation were analyzed in
      109 patients. Twenty-six 2-dimensional and Doppler parameters were assessed for
      their association with the primary outcome of 30-day RVF, defined as a
      requirement of an RV assist device or >= 14 consecutive days of inotropic
      support, and the secondary composite outcome of 30-day death or RVF. Multivariate
      analysis adjusted for known clinical risk prediction models was performed.
      RESULTS: Overall, 25 (22.9%) and 27 (24.8%) patients reached the primary and
      secondary end-points, respectively. An increased RV/LV diameter ratio was the
      only TTE variable independently associated with both the primary (odds ratio [OR]
      = 5.40; 95% confidence interval [CI] 2.40 to 12.40; p = 0.012) and secondary (OR
      = 2.70; 95% CI 1.06 to 6.22; p = 0.03) outcomes after multivariate analysis.
      Scatterplot analysis with regression determined the optimal cut-off value for
      RV/LV diameter to be 0.75. Based on receiver operating characteristic curves, an
      increased RV/LV diameter ratio provided an additional predictive value to
      clinical risk scores. CONCLUSIONS: A TTE-measured RV/LV diameter ratio of >=0.75
      is independently associated with a higher risk for RVF in patients with
      continuous-flow LVAD. When used alone, this simple, easily derived, practical
      echocardiographic measurement has a predictive value equivalent to known clinical
      risk scores, whereas their combination provides stronger risk prediction for
      adverse outcomes.

PMID- 23856217
TI  - Changes in body composition after lung transplantation in children.
AB  - BACKGROUND: The evaluation of nutritional status, including body composition
      measurements, in pediatric patients before and after lung transplant (LTx) can
      aid in adapting nutrition support and physical rehabilitation programs to meet
      individual patient needs. The purpose of this retrospective study was to
      determine the changes in weight, lean body mass (LBM), and body fat (BF) before
      and after LTx and their association with lung function in pediatric patients.
      METHODS: Included were 41 LTx patients, aged 3 months to 20.7 years, who had at
      least 2 body composition measurements determined by dual-energy X-ray
      absorptiometry (GE Lunar Prodigy, Waukesha, WI) in the first 2 years after LTx
      were measured pre-LTX and at 12 or 24 months post-LTX, for weight, LBM, and BF.
      RESULTS: Pre-LTx, 29% of patients had moderate and 12% had severe chronic
      malnutrition (growth stunting). This compares with 21% of patients being
      moderately LBM-depleted and 23% being BF-depleted. The weight change at 12 and 24
      months was +9.3% (interquartile range, 5.6%-23%) and +4.7% (0.9%-11.6%),
      respectively; whereas the LBM change at 12 and 24 months was +15.2% (6.8%-17.1%)
      and +4.2% (-0.6% to 7.7%), respectively. LBM percentiles correlated with
      pulmonary function tests ( % predicted forced vital capacity [rho = 0.36, p =
      0.001] and forced expiratory volume in 1 second [rho = 0.265, p = 0.015).
      CONCLUSIONS: Maximum weight and LBM gain occur at 12 months after LTx, with
      smaller gains noted at 24 months. Clinicians must look beyond height and weight
      and evaluate LBM and fat mass in pediatric patients after LTx.

PMID- 23856218
TI  - Pre-transplant antibodies to Kalpha1 tubulin and collagen-V in lung
      transplantation: clinical correlations.
AB  - BACKGROUND: Immune responses to lung-associated self-antigens (SAgs) have been
      implicated in chronic lung allograft rejection. The goals of this study were to
      determine the prevalence of pre-existing antibodies (Abs) to the SAgs in
      pulmonary diseases and the association between pre-existing Abs to SAgs and the
      development of primary graft dysfunction (PGD), donor-specific antibodies (DSA),
      and chronic rejection. METHODS: Pre- and post-transplant sera were analyzed from
      317 lung transplant (LTx) recipients between 2000 and 2011 with diagnosis of
      chronic obstructive disease (n = 161), idiopathic pulmonary fibrosis (IPF; n =
      50), cystic fibrosis (CF; n = 55), and others (n = 51). Samples were analyzed for
      Abs to SAgs by enzyme-linked immunosorbent assay, and DSA and cytokines by
      Luminex. The clinical diagnosis of PGD and bronchiolitis obliterans syndrome
      (BOS) was based on International Society for Heart and Lung Transplantation
      guidelines. RESULTS: The overall prevalence of Abs to SAgs was 22.71%, including
      18% in chronic obstructive pulmonary disease (p = 0.033), 34% in IPF (p =
      0.0006), 29% in CF (p = 0.0023), and 19.6% in other diagnoses (p = 0.044). The
      incidence of PGD (88% vs 54%, p < 0.05), DSA (70% vs 45%, p < 0.01), and BOS (90%
      vs 38% (p < 0.001) after LTx was significantly higher in patients with pre-LTx
      Abs to SAgs than without. Pro-inflammatory cytokines (interleukin-1beta,
      interleukin-17, and interferon-gamma) were elevated in patients who had pre-LTx
      Abs to SAgs, along with a reduction in anti-inflammatory interleukin-10.
      CONCLUSIONS: Patients with IPF and CF have the highest prevalence of Abs to SAgs.
      Patients with pre-existing Abs to SAgs are at increased risk for development of
      PGD, DSA, and BOS. Strategies to remove pre-existing Abs to SAgs should be
      considered to improve lung allograft outcome.

PMID- 23856220
TI  - Initial topical cooling followed by backtable Celsior flush perfusion provides
      excellent early graft function in porcine single lung transplantation after 24
      hours of cold ischemia.
AB  - BACKGROUND: Topical in situ cooling of the donor lungs is a prerequisite for
      procurement of non-heart-beating donor lungs and may be of interest for living
      related lung donation. METHODS: Twenty-four single lung transplants were
      performed in 4 groups of Landrace pigs (6 per group). Control LPD, control
      Celsior and topical cooling in situ, followed by LPD (exLPD) or Celsior (exCel)
      ex situ flush, were employed. All lungs were perfused antegrade with 1 liter of
      solution at 4 degrees C. Lungs were stored immersed in preservation solution for
      24 hours at 4 degrees C. After transplantation of the left lung, the right
      recipient bronchus and pulmonary artery were clamped. RESULTS: Four of 6 animals
      each in the LPD and Celsior groups and all 6 animals in both the exLPD and the
      exCel groups survived the 7-hour reperfusion. The mean oxygenation index was
      favorably preserved in the exCel group at 7 hours after reperfusion (417 +/- 81)
      over all other groups (LPD 341 +/- 133, Celsior 387 +/- 86, exLPD 327 +/- 76; p <
      0.0001). Pulmonary vascular resistance showed significantly lower values in the
      Celsior and exCel groups (LPD 1,310 +/- 620, Celsior 584 +/- 194, exLPD 1,035 +/-
      361, exCel 650 +/- 116 dyn/s/cm(5) at 7 hours after reperfusion; p < 0.0001).
      Consistently, the wet-to-dry lung weight ratio also indicated beneficial graft
      protection in the exCel group (LPD 8.1 +/- 0.8, Celsior 8.4 +/- 0.8, exLPD 7.5 +/
      1.0, exCel 3.1 +/- 0.9; p < 0.0001). CONCLUSION: Initial topical cooling
      followed by backtable perfusion is a sufficient technique for pulmonary graft
      preservation providing excellent post-transplant function. Celsior subsequent to
      in-situ topical cooling revealed the most beneficial results in this setting.
      This combined technique could advance non-heart-beating, living related lung lobe
      donation and, potentially, regular heart-beating lung donation.

PMID- 23856219
TI  - Partial mechanical circulatory support in an ovine model of post-infarction
      remodeling.
AB  - BACKGROUND: Full unloading of the left ventricle (LV) in chronic heart failure
      (CHF) induces reversal of LV dilation and geometric distortion. In this study we
      describe the partial unloading effects in ischemic CHF. METHODS: Six weeks after
      myocardial infarction, sheep were randomized to partial support ("pump," n = 5),
      as provided by the CircuLite Synergy micro-pump, or to no therapy ("sham," n = 6)
      for an additional 6 weeks. At baseline, and at 6 and 12 weeks after infarction,
      pressure-volume (PV) recordings were made. Systolic and diastolic functions were
      characterized by the end-systolic volume (ESV) where LV end-systolic pressure
      reached 90 mm Hg (V90), and the end-diastolic volume (EDV) where LV end-diastolic
      pressure reached 15 mm Hg (V15), respectively. Magnetic resonance imaging (MRI)
      was performed 6 and 12 weeks after infarction. During autopsy at 12 weeks,
      isolated LVs were weighed. Histologically, the degree of fibrosis in the non
      infarcted area was assessed using systematic randomized sampling, and myocyte
      hypertrophy was measured by the mean linear intercept method. RESULTS: At 6
      weeks, PV measurements showed a V90 and V15 increase (p = NS between groups). Six
      weeks later, V90 and V15 increased in the sham group. In the pump group, V90
      decreased but V15 did not change significantly. At 6 weeks, MRI indicated no
      significant difference between groups. Six weeks later, in the sham group, EDV
      and ESV increased significantly. In the pump group, EDV decreased significantly
      and ESV trended to decrease. Sphericity index increased in the sham group and
      decreased in the pump group, although not significantly. Explanted LV masses were
      significantly higher in the sham group than in the pump group. The pump group had
      a decrease in fibrosis and less myocyte hypertrophy. CONCLUSION: Partial support
      6 weeks after major myocardial infarction halts and reverses ventricular dilation
      and hypertrophy.

PMID- 23856221
TI  - Left ventricular retraining after arterial switch operation facilitated by
      mechanical circulatory support.

PMID- 23856222
TI  - "Flexo-dyspnea": A novel clinical observation in the heart failure syndrome.

PMID- 23856223
TI  - [Efficacy, tolerance and safety of polyethylene glycol 3350 plus electrolytes for
      the treatment of functional constipation in children].
AB  - OBJECTIVE: To assess the renal safety of treatment with polyethylene glycol 3350
      with electrolytes at 1, 3 and 6 months, its gastrointestinal tolerance and dose
      effectiveness. PATIENTS AND METHODS: Three groups of 30 healthy patient aged 2-10
      years (mean 6.2 years) who suffered functional constipation (Rome III criteria)
      with 1, 3 and 6 months of treatment were evaluated. Efficacy was evaluated by the
      change in the number of stools per week and stool consistency (Bristol scale).
      Urine screens, sodium and osmolality, were performed at the beginning and after
      1, 3 and 6 months of treatment. Stool sample NIRA (near-infrared reflectance
      analysis) and hydrogen breath test analysis samples were performed on the one
      month treatment group. RESULTS: The mean dose was 0.37g/kg/day (range 0.18 to
      0.8) titrated according to age, weight and response. The number of stools per
      week during treatment (2.4+/-0.64) showed a significant difference (P<.001) vs
      (6.21+/-1.5) after treatment. There was also a significant difference in the
      Bristol scale score (1.9+/-0.75 vs 4.9+/-1.1 [P<.001]). The mean sodium intake
      was 112mg (5mg/kg/day [range 4-12mg/kg/day]). The values of sodium and urine
      osmolality were normal in all groups with no statistical difference compared to
      normal control values (90 healthy children without treatment). NIRA values were
      normal in all patients. The hydrogen breath test was normal with a median of
      7ppm. CONCLUSION: There were no adverse renal biochemical parameters or
      gastrointestinal disorders. Tolerance and efficacy was shown to be optimal.
      Polyethylene glycol 3350 with electrolytes can be safely recommended for the
      treatment of functional constipation in children in the short and long term.

PMID- 23856224
TI  - Including Life Cycle Assessment for decision-making in controlling wastewater
      nutrient removal systems.
AB  - This paper focuses on the use of Life Cycle Assessment (LCA) to evaluate the
      performance of seventeen control strategies in wastewater treatment plants
      (WWTPs). It tackles the importance of using site-specific factors for nutrient
      enrichment when decision-makers have to select best operating strategies.
      Therefore, the LCA evaluation is repeated for three different scenarios depending
      on the limitation of nitrogen (N), phosphorus (P), or both, when evaluating the
      nutrient enrichment impact in water bodies. The LCA results indicate that for
      treated effluent discharged into N-deficient aquatic systems (e.g. open coastal
      areas) the most eco-friendly strategies differ from the ones dealing with
      discharging into P-deficient (e.g. lakes and rivers) and N&P-deficient systems
      (e.g. coastal zones). More particularly, the results suggest that strategies that
      promote increased nutrient removal and/or energy savings present an environmental
      benefit for N&P and P-deficient systems. This is not the case when addressing N
      deficient systems for which the use of chemicals (even for improving N removal
      efficiencies) is not always beneficial for the environment. A sensitivity
      analysis on using weighting of the impact categories is conducted to assess how
      value choices (policy decisions) may affect the management of WWTPs. For the
      scenarios with only N-limitation, the LCA-based ranking of the control strategies
      is sensitive to the choice of weighting factors, whereas this is not the case for
      N&P or P-deficient aquatic systems. 

PMID- 23856226
TI  - Responsive polymers for analytical applications: a review.
AB  - Stimuli-responsive polymers are capable of translating changes in their local
      environment to changes in their chemical and/or physical properties. This ability
      allows stimuli-responsive polymers to be used for a wide range of applications.
      In this review, we highlight the analytical applications of stimuli-responsive
      polymers that have been published over the past few years with a focus on their
      applications in sensing/biosensing and separations. From this review, we hope to
      make clear that while the history of using stimuli-responsive polymers for
      analytical applications is rich, there are still a number of directions to
      explore and exciting advancements to be made in this flourishing field of
      research. 

PMID- 23856225
TI  - Magnetic materials as sorbents for metal/metalloid preconcentration and/or
      separation. A review.
AB  - The use of magnetic materials in solid phase extraction has received considerable
      attention in recent years taking into account many advantages arising from the
      inherent characteristics of magnetic particles. Magnetic solid phase extraction
      (MSPE) methodology overcomes problems such as column packing and phase
      separation, which can be easily performed by applying an external magnetic field.
      The use of magnetic particles in automatic systems is growing over the last few
      years making the on-line operation of MSPE a promising technique in the frame of
      green chemistry. This article aims to provide all recent progress in the research
      of novel magnetic materials as sorbents for metal preconcentration and
      determination coupled with different detection systems as well as their
      implementation in sequential injection and microfluidic systems. In addition, a
      description of preparation, characterization as well as applications of various
      types of magnetic materials, either with organic or inorganic coating of the
      magnetic core, is presented. Concluding remarks and future trends are also
      commented. 

PMID- 23856227
TI  - Advantages and effects of nitrogen doping into the central channel of plasma in
      axially viewed-inductively coupled plasma optical emission spectrometry.
AB  - The effects and benefits of N2 addition to the central channel of the ICP through
      the nebulizer gas used in ICP OES with axial view configuration were investigated
      in the present study. The N2 flow rate, nebulizer gas flow rate, RF power and
      sample uptake rate were evaluated and compared for two sample introduction
      systems (pneumatic nebulization/aerosol desolvation and conventional pneumatic
      nebulization). It was observed that N2 did not affect solution nebulization and
      aerosol transport but affects the ICP characteristics. The higher thermal
      conductivity of N2 (in comparison with Ar) changes energy distribution in the
      ICP, observed by monitoring the signals of Ar emission lines and sodium emission.
      The ratio Mg(II)-280.270 nm/Mg(I)-285.213 nm was utilized as a diagnostic tool
      for plasma robustness. The addition of N2 (20 mL min(-1)) increased plasma
      robustness significantly and mitigated effects caused by Na, K and Ca. For 40
      spectral lines evaluated, it was observed that the emission signals of ionic
      spectral lines were in general more affected by N2 than those of atomic spectral
      lines. Detection limits, precision, sensitivity and linearity of calibration
      curves obtained using N2-Ar-ICP were almost similar to those obtained using Ar
      ICP. The analysis of 5 different reference materials revealed that accuracy was
      not degraded by adding N2 to the Ar-ICP.

PMID- 23856228
TI  - Enzymatic activity and catalytic hydrogen evolution in reduced and oxidized
      urease at mercury surfaces.
AB  - It was originally shown [10] that urease retains its enzymatic activity when
      adsorbed at bare mercury and solid amalgam surfaces. However the opinion later
      prevailed that, when adsorbed at bare metal electrodes, proteins are irreversibly
      denatured. Here we confirm that urease is enzymatically active at a bare solid
      amalgam surface as found by Santhanam et al., and we show that this enzyme is
      equally active at a thiol-modified amalgam surface. We also show that it is the
      reduced form of urease, which is enzymatically active at Hg surfaces. Oxidation
      of the protein, resulting in formation of disulfide bonds, strongly decreases the
      enzyme activity. Using constant current chronopotentiometric stripping (CPS) we
      show that the exposure of surface-attached urease to negative potentials results
      in the protein unfolding. The extent of the unfolding depends upon the amount of
      time for which the protein is exposed to negative potentials, and at very short
      times this unfolding can be avoided. At thiol-modified Hg surfaces the protein is
      less vulnerable to the effects of the electric field. We conclude that the loss
      of enzymatic activity, resulting from a 10 min exposure of the protein to -0.58
      V, is not due to reduction of the disulfide bonds as suggested by Santhanam et
      al. This loss is probably a result of protein reorientation, due to reduction of
      the Hg-S bonds (formed by accessible cysteines), followed by prolonged electric
      field effect on the surface-attached protein.

PMID- 23856229
TI  - Efficient hydrophobization and solvent microextraction for determination of trace
      nano-sized silver and titanium dioxide in natural waters.
AB  - Hydrophobic silver and titanium (IV) oxide nanoparticles (commercial Ag and TiO2
      NPs with average particle sizes of 17 and 19 nm, respectively) were
      quantitatively transferred into organic phase in natural water samples. Five NP
      surface modification and solvent extraction agents (reagents) types,
      mercaptocarboxylic acid, alkylamine, mediator solvent, extraction solvent, and
      surfactant, were investigated and optimized with three-level orthogonal array
      design (OAD), an OA27 (3(13)) matrix. The most favorable reagents and
      experimental conditions were then examined. The best extraction efficiencies of
      78.6 and 73.7% were obtained for 1 mg L(-1) citrate-stabilized Ag and TiO2 NPs,
      respectively, with 0.5 mM of 11-mercaptoundecanoic acid, 1.5 mM of
      octadecylamine, 1 mL of methanol, 150 MUL of cyclohexane, 0.05 mM of tetra-n
      octylammonium bromide, pH=8.0, adsorption time of 2h, sonication time of 3 min,
      and centrifugation time of 10 min. Enrichment factors were 97 and 83, for Ag and
      TiO2 NPs, respectively. The optimum extraction conditions were successfully
      applied to genuine water samples at spiking levels of 2-100 MUg L(-1) of Ag and
      TiO2 NPs. The relative recoveries of (69.0-85.1)% and (61.5-78.5)% were obtained
      for Ag and TiO2 NPs, respectively. The extracted surface-modified NPs were
      characterized with transmission electron microscopy, selected area electron
      diffraction, energy-dispersive X-ray, ultraviolet-visible, and Fourier transform
      infrared spectroscopic techniques. Based on the results, efficient ligand
      exchange and acid-base pair formation were observed on the NP surface without
      significant change in its original properties. The organic phase was microwave
      digested, and analyzed with inductively coupled plasma (ICP) optical emission
      spectroscopy and ICP mass spectrometry (ICP-MS). Detection limits of ICP-MS
      analyses of Ag and TiO2 NPs were 0.02 and 0.07 MUg L(-1), respectively.

PMID- 23856231
TI  - Sequential determination of fat- and water-soluble vitamins in Rhodiola imbricata
      root from trans-Himalaya with rapid resolution liquid chromatography/tandem mass
      spectrometry.
AB  - A rapid method was developed to determine both types of vitamins in Rhodiola
      imbricata root for the accurate quantification of free vitamin forms. Rapid
      resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) with
      electrospray ionization (ESI) source operating in multiple reactions monitoring
      (MRM) mode was optimized for the sequential analysis of nine water-soluble
      vitamins (B1, B2, two B3 vitamins, B5, B6, B7, B9, and B12) and six fat-soluble
      vitamins (A, E, D2, D3, K1, and K2). Both types of vitamins were separated by ion
      suppression reversed-phase liquid chromatography with gradient elution within 30
      min and detected in positive ion mode. Deviations in the intra- and inter-day
      precision were always below 0.6% and 0.3% for recoveries and retention time.
      Intra- and inter-day relative standard deviation (RSD) values of retention time
      for water- and fat-soluble vitamin were ranged between 0.02-0.20% and 0.01-0.15%,
      respectively. The mean recoveries were ranged between 88.95 and 107.07%.
      Sensitivity and specificity of this method allowed the limits of detection (LOD)
      and limits of quantitation (LOQ) of the analytes at ppb levels. The linear range
      was achieved for fat- and water-soluble vitamins at 100-1000 ppb and 10-100 ppb.
      Vitamin B-complex and vitamin E were detected as the principle vitamins in the
      root of this adaptogen which would be of great interest to develop novel foods
      from the Indian trans-Himalaya.

PMID- 23856230
TI  - Speciation of chromium in environmental samples by dual electromembrane
      extraction system followed by high performance liquid chromatography.
AB  - This study proposes the dual electromembrane extraction followed by high
      performance liquid chromatography for selective separation-preconcentration of
      Cr(VI) and Cr(III) in different environmental samples. The method was based on
      the electrokinetic migration of chromium species toward the electrodes with
      opposite charge into the two different hollow fibers. The extractant was then
      complexed with ammonium pyrrolidinedithiocarbamate for HPLC analysis. The effects
      of analytical parameters including pH, type of organic solvent, sample volume,
      stirring rate, time of extraction and applied voltage were investigated. The
      results showed that Cr(III) and Cr(VI) could be simultaneously extracted into the
      two different hollow fibers. Under optimized conditions, the analytes were
      quantified by HPLC instrument, with acceptable linearity ranging from 20 to 500
      MUg L(-1) (R(2) values>=0.9979), and repeatability (RSD) ranging between 9.8% and
      13.7% (n=5). Also, preconcentration factors of 21.8-33 that corresponded to
      recoveries ranging from 31.1% to 47.2% were achieved for Cr(III) and Cr(VI),
      respectively. The estimated detection limits (S/N ratio of 3:1) were less than
      5.4 MUg L(-1). Finally, the proposed method was successfully applied to determine
      Cr(III) and Cr(VI) species in some real water samples.

PMID- 23856232
TI  - Accurate mass determination, quantification and determination of detection limits
      in liquid chromatography-high-resolution time-of-flight mass spectrometry:
      challenges and practical solutions.
AB  - Uniform guidelines for the data processing and validation of qualitative and
      quantitative multi-residue analysis using full-spectrum high-resolution mass
      spectrometry are scarce. Through systematic research, optimal mass accuracy and
      sensitivity are obtained after refining the post-processing of the HRMS data. For
      qualitative analysis, transforming the raw profile spectra to centroid spectra is
      recommended resulting in a 2.3 fold improved precision on the accurate mass
      determination of spectrum peaks. However, processing centroid data for
      quantitative purposes could lead to signal interruption when too narrow mass
      windows are applied for the construction of extracted ion chromatograms.
      Therefore, peak integration on the raw profile data is recommended. An optimal
      width of the mass window of 50 ppm, which is a trade-off between sensitivity and
      selectivity, was obtained for a TOF instrument providing a resolving power of
      20,000 at full width at half maximum (FWHM). For the validation of HRMS
      analytical methods, widespread concepts such as the signal-to-noise ratios for
      the determination of decision limits and detection capabilities have shown to be
      not always applicable because in some cases almost no noise can be detected
      anymore. A statistical methodology providing a reliable alternative is extended
      and applied.

PMID- 23856233
TI  - Real-time cell-microelectronic sensing of nanoparticle-induced cytotoxic effects.
AB  - We report a real-time cell analysis (RTCA) sensing method of 96 electronic
      microwells for profiling the cytotoxicity of nanoparticles on different cell
      lines. The method consists of 96 microwells embedded with microelectrodes (96x E
      plate) to measure impedance changes of adherent cell lines. When the testing
      cells change in population, adhesion, and/or morphology, the impedance at the
      cell-electrode interface changes to provide real-time monitoring of overall cell
      status. To demonstrate this technique, we used three cell lines as sensing
      probes: two human lung carcinoma cell lines, A549 and SK-MES-1, and a normal
      mammalian cell line, CHO-K1. We tested two well-characterized nanoparticles: nano
      titanium dioxide (nTiO2) and nano-silver (nAg). The three cell lines were
      separately seeded into 96x E-plates and treated with varying concentrations of
      nanoparticles (0.078-160 MUg mL(-1)). This method provides dynamic cell response
      profiles and temporal IC50 histograms, showing concentration-, time-, particle-,
      and cell-dependent cytotoxicity. The 24 h and 48 h IC50 values of nAg obtained
      using both the RTCA and the neutral red uptake (NRU) assays were in good
      agreement, validating the RTCA technique. The RTCA assay does not suffer
      interference from nTiO2, whereas the NRU assay cannot be used due to severe
      interference from nTiO2. A cytostatic response was observed in CHO-K1 cells after
      24 h exposure to 40 MUg mL(-1) nTiO2, which was correlated with S-phase cell
      cycle arrest based on cell cycle analysis using flow cytometry. This suggests
      that the shapes of the response curves provide indicative information, directing
      further studies into the mode of action of the toxicant. Advantages of the RTCA
      technique over traditional colorimetric assays for screening the cytotoxicity of
      nanoparticles include minimizing interference, qualitative and quantitative
      cytotoxicity data, and the capability of real-time and high-throughput
      measurements.

PMID- 23856234
TI  - Preparation and evaluation of an immunoaffinity sorbent with Fab' antibody
      fragments for the analysis of opioid peptides by on-line immunoaffinity solid
      phase extraction capillary electrophoresis-mass spectrometry.
AB  - An immunoaffinity (IA) sorbent with antibody fragments was prepared for the
      analysis of opioid peptides by on-line immunoaffinity solid-phase extraction
      capillary electrophoresis-mass spectrometry (IA-SPE-CE-MS). The antibody
      fragmentation was evaluated by MALDI-TOF-MS. Fab' fragments obtained from a
      polyclonal IgG antibody against Endomorphins 1 and 2 (End1 and End2) were
      covalently attached to succinimidyl silica particles to prepare the IA sorbent.
      An IA-SPE-CE-MS methodology was established analyzing standard solutions of End1
      and End2 and acceptable repeatability, linearity ranges and LODs (0.5 and 5 ng
      mL(-1), respectively) were obtained. The LOD of End1 was slightly better than
      that previously obtained using an IA sorbent with intact antibodies (1 ng mL(
      1)). In human plasma samples, End1 and End2 could be detected at 1 and 50 ng mL(
      1), respectively, which meant an improvement of 100 and 2-fold with regard to the
      LODs using an IA sorbent with intact antibodies (100 ng mL(-1)).

PMID- 23856235
TI  - On-line capillary electrophoresis enrichment by combining chitosan trapping with
      surfactant assisted sample stacking for the ultratrace determination of organic
      acids in Plateau alfalfa roots.
AB  - In this paper, four organic acids constituents of Plateau alfalfa roots have been
      identified and detected by a novel capillary electrophoresis (CE) strategy which
      combined chitosan (CS) trapping and cetyltrimethyl ammonium bromide (CTAB)
      assisted sample stacking. Under the optimized condition, organic acids, i.e.,
      aconitic acid, gallic acid, citric acid and l-malic acid were concentrated and
      separated within 3 min. Validation parameters of this method (such as detection
      limits, linearity and precision) were also investigated and the limit of
      detection (LOD) was 2.41-53.9 ng mL(-1). Linearity was obtained over the
      magnitude range of 5-4000 ng mL(-1) approximately for different organic acids and
      3*10(2)-1.5*10(4) folds enrichment was achieved. The method has been applied to
      the determination of organic acids in roots of normal grown Plateau alfalfa and
      stressing affected Plateau alfalfa. Satisfactory results and recoveries were
      obtained in the analysis without costly and complicated sample pretreatment.

PMID- 23856236
TI  - Look now and hear what's coming: on the functional role of cross-modal phase
      reset.
AB  - In our multisensory environment our sensory systems are continuously receiving
      information that is often interrelated and must be integrated. Recent work in
      animals and humans has demonstrated that input to one sensory modality can reset
      the phase of ambient cortical oscillatory activity in another. The periodic
      fluctuations in neuronal excitability reflected in these oscillations can thereby
      be aligned to forthcoming anticipated sensory input. In the auditory domain, the
      example par excellence is speech, because of its inherently rhythmic structure.
      In contrast, fluctuations of oscillatory phase in the visual system are argued to
      reflect periodic sampling of the environment. Thus rhythmic structure is imposed
      on, rather than extracted from, the visual sensory input. Given this distinction,
      we suggest that cross-modal phase reset subserves separate functions in the
      auditory and visual systems. We propose a modality-dependent role for cross-modal
      input in temporal prediction whereby an auditory event signals the visual system
      to look now, but a visual event signals the auditory system that it needs to hear
      what is coming. This article is part of a Special Issue entitled <Human Auditory
      Neuroimaging>. 

PMID- 23856238
TI  - Tutors' opinions of suitability of online learning programmes in continuing
      professional development for midwives.
AB  - BACKGROUND: Online learning is frequently used in continuing professional
      development for qualified nurses and midwives. It is frequently assumed that the
      same package is appropriate for different groups of learners and that by reducing
      the need for tutorial input, tutorial time is saved. OBJECTIVES: We evaluated the
      suitability of an online learning resource for suitability in continuing
      professional development for midwives. Originally developed for use as part of a
      work-based package for a specific audience, there had always been plans for more
      general use of the resource with other groups of health workers. DESIGN:
      Sequential mixed methods study. SETTING: English universities. PARTICIPANTS:
      Seventy university tutors. METHODS: Online questionnaire and in-depth interviews.
      FINDINGS: Tutors did not consider that the online learning materials would be
      suitable for a wider audience without significant adaptation. They thought that
      uptake would increase need for tutorial input. CONCLUSION: Our findings
      demonstrate the pitfalls of removing learning from the context of practice.
      Technology customised to meet the needs of one group of learners probably does
      not have the potential for transfer to another group without significant
      adaptation. Those responsible for designing e-learning should take into account
      the needs of all the different audiences for whom the resource is intended from
      the outset, with consideration for the context in which learning will be applied
      to practice and how students will be supported. If the same package is to be used
      by different audiences and in different settings, tutors and students will
      require explicit instructions of how they should use the resource and depth of
      knowledge and level of competency that should be attained at the conclusion of
      the programme.

PMID- 23856237
TI  - Lithium alters the morphology of neurites regenerating from cultured adult spiral
      ganglion neurons.
AB  - The small-molecule drug lithium (as a monovalent ion) promotes neurite
      regeneration and functional recovery, is easy to administer, and is approved for
      human use to treat bipolar disorder. Lithium exerts its neuritogenic effect
      mainly by inhibiting glycogen synthase kinase 3, a constitutively-active
      serine/threonine kinase that is regulated by neurotrophin and "wingless-related
      MMTV integration site" (Wnt) signaling. In spiral ganglion neurons of the
      cochlea, the effects of lithium and the function of glycogen synthase kinase 3
      have not been investigated. We, therefore, set out to test whether lithium
      modulates neuritogenesis from adult spiral ganglion neurons. Primary cultures of
      dissociated spiral ganglion neurons from adult mice were exposed to lithium at
      concentrations between 0 and 12.5 mM. The resulting neurite morphology and growth
      cone appearance were measured in detail by using immunofluorescence microscopy
      and image analysis. We found that lithium altered the morphology of regenerating
      neurites and their growth cones in a differential, concentration-dependent
      fashion. Low concentrations of 0.5-2.5 mM (around the half-maximal inhibitory
      concentration for glycogen synthase kinase 3 and the recommended therapeutic
      serum concentration for bipolar disorder) enhanced neurite sprouting and
      branching. A high concentration of 12.5 mM, in contrast, slowed elongation. As
      the lithium concentration rose from low to high, the microtubules became
      increasingly disarranged and the growth cones more arborized. Our results
      demonstrate that lithium selectively stimulates phases of neuritogenesis that are
      driven by microtubule reorganization. In contrast, most other drugs that have
      previously been tested on spiral ganglion neurons are reported to inhibit neurite
      outgrowth or affect only elongation. Lithium sensitivity is a necessary, but not
      sufficient condition for the involvement of glycogen synthase kinase 3. Our
      results are, therefore, consistent with, but do not prove lithium inhibiting
      glycogen synthase kinase 3 activity in spiral ganglion neurons. Experiments with
      additional drugs and molecular-genetic tools will be necessary to test whether
      glycogen synthase kinase 3 regulates neurite regeneration from spiral ganglion
      neurons, possibly by integrating neurotrophin and Wnt signals at the growth cone.

PMID- 23856239
TI  - Using lecture capture: a qualitative study of nursing faculty's experience.
AB  - BACKGROUND: As lecture capture technology becomes widely available in schools of
      nursing, faculty will need to master new technological skills and make decisions
      about recording their classroom lectures or other activities. OBJECTIVES: This
      study sought to understand faculty's experience of using a new lecture capture
      system. DESIGN AND SETTING: This qualitative study used Kruger's systematic
      approach to explore undergraduate nursing faculty's first-time experience using a
      lecture capture system purchased by the university. METHOD: Four focus groups
      were conducted with a total of fourteen undergraduate faculty using lecture
      capture for the first-time. The interviews were recorded and transcribed and then
      analyzed by the researchers. RESULTS: Four themes were identified from the
      faculty interviews. Two of the themes expressed faculty's concerns about the
      teaching role, and two themes expressed the faculty's concerns about student
      learning. CONCLUSION: Participants experienced stress when learning to use the
      new lecture capture technology and struggled to resolve it with their own beliefs
      and teaching values. The impact of lecture capture on student learning, impact on
      class attendance, and the promotion of a culture of lecturing were revealed as
      important issues to consider when lecture capture becomes available.

PMID- 23856241
TI  - Hypothesis on two different functionalities co-existing in frontal lobe of human
      brains.
AB  - Human frontal lobe is a key area from where our cognition, memory and emotion
      display or function. In medical case study, there are patients with social
      dysfunctions, lack of passion or emotion as result of their frontal lobe damage
      caused by pathological changes, traumatic damage, and brain tumor remove
      operations. The syndrome of frontal lobe damage remains at large unanswered
      medically. From early stage of pregnancy, there exists lobe layers, nerve
      combine, and neurons synaptic, indicating a completion of growth of functionality
      inside frontal lobe. However, this completion of growth does not match the growth
      of human intelligence. Human infants only start and complete their cognition and
      memory functionality one full year after their birth which is marked by huge
      amount of neurons synaptic inside their frontal lobe, which is not part of a
      continual growth of originally developed functions. By reasoning on pathological
      changes of frontal lobe, a hypothesis was established that two individually
      functional mechanisms co-existed inside one frontal lobe. This neuron system is
      particularly for human beings. 

PMID- 23856240
TI  - Use of expression-enhancing terminators in Saccharomyces cerevisiae to increase
      mRNA half-life and improve gene expression control for metabolic engineering
      applications.
AB  - Control of gene and protein expression of both endogenous and heterologous genes
      is a key component of metabolic engineering. While a large amount of work has
      been published characterizing promoters for this purpose, less effort has been
      exerted to elucidate the role of terminators in yeast. In this study, we
      characterize over 30 terminators for use in metabolic engineering applications in
      Saccharomyces cerevisiae and determine mRNA half-life changes to be the major
      cause of the varied protein and transcript expression level. We demonstrate that
      the difference in transcript level can be over 6.5-fold even for high strength
      promoters. The influence of terminator selection is magnified when coupled with a
      low-expression promoter, with a maximum difference in protein expression of 11
      fold between an expression-enhancing terminator and the parent plasmid terminator
      and over 35-fold difference when compared with a no-terminator baseline. This is
      the first time that terminators have been investigated in the context of multiple
      promoters spanning orders of magnitude in activity. Finally, we demonstrate the
      utility of terminator selection for metabolic engineering by using a mutant
      xylose isomerase gene as a proof-of-concept. Through pairing an expression
      enhancing terminator with a low-expression promoter, we were able to achieve the
      same phenotypic result as with a promoter considerably higher in strength.
      Moreover, we can further boost the phenotype of the high-strength promoter by
      pairing it with an expression-enhancing terminator. This work highlights how
      terminator elements can be used to control metabolic pathways in the same way
      that promoters are traditionally used in yeast. Together, this work demonstrates
      that terminators will be an important part of heterologous gene expression and
      metabolic engineering for yeast in the future. 

PMID- 23856242
TI  - The relationship between mood instability and depression: implications for
      studying and treating depression.
AB  - BACKGROUND: Most individuals with depressed mood report mood fluctuations (Mood
      Instability) within hours or days. This is not recognized in diagnostic criteria
      or standard rating scales for depression. HYPOTHESIS: That mood instability is a
      distinct component of the development of depression that has been omitted from
      criteria for depression because of reliance on retrospective recall and
      structured interviews. The inclusion of Mood Instability would enhance research
      into causes and treatment of depression. STUDIES: We examined three datasets that
      used retrospective and prospective measures of depressed symptom ratings and mood
      instability to determine the relationship between the two. Study 1 used data from
      the 1991 UK Health and Lifestyle Surveys (HALS). Studies 2 and 3 used clinical
      samples. The scales used to assess mood instability were the mood instability
      factor from the Eysenck Personality Inventory Neuroticism Scale, the Affective
      Lability Scale (ALS), and the Visual Analogue Depression Scale (VAS). The
      depression scales (depressive symptoms) were the General Health Questionnaire
      (GHQ) depression factor, the Beck Depression Inventory IA (BDI) and the mean from
      the Visual Analogue Depression Scale (VAS). We used partial correlation analysis
      to assess the association between mood instability and depression and exploratory
      factor analysis to determine the factor structure of items pooled from the mood
      instability and depression scales from studies 1 and 2. RESULTS: Mood Instability
      was found to be moderately associated with depressive symptoms. The Pearson's r
      values ranged from 0.49 to 0.57. The correlation was lower when recalling mood in
      the past. The factor analytic solution supported the hypothesis that MI and
      depressive symptoms are related but distinct constructs. CONCLUSIONS: Reliance
      exclusively on the retrospective assessment of depressive symptoms has occluded
      the widespread occurrence of mood instability. Including Mood Instability in
      diagnostic and assessment criteria would enhance causal and treatment research in
      depression.

PMID- 23856243
TI  - The meaning of the anti-cancer antibody CLN-IgG (Pritumumab) generated by human *
      human hybridoma technology against the cyto-skeletal protein, vimentin, in the
      course of the treatment of malignancy.
AB  - Cancer stem cells in a tumor mass form a very small subpopulation ranging from
      below 0.1% in a brain tumor but they have the crucial ability to become
      malignant. The goal of cancer therapy has been the total killing of tumor cells.
      However we should clarify that most of all tumor cells are differentiated cancer
      cells. Thus the elimination of 99.9% of tumor cells under histological criteria
      cannot ensure the cancer will be cured. Rather cancer cell biologists should turn
      their attention to reprogramming cancer stem cells to normal stem cells by which
      malignancy recuperates normal organogenesis from the aspect of the dichotomy of
      cancer stem cell. The cue points underlying the reverse cancer stem cell at
      blastogenesis in inflammation site is depending upon cell-to-cell recognition of
      the tumor-niche cells. Normalization of tumor-niche promises to lead cancer stem
      cell into normal stem cell owing to autonomous healing mechanisms that reside in
      the self-defense mechanisms in immunity and the cell competition mechanisms in
      the wound healing of the tissue cells. Among the cyto-skeletal proteins, vimentin
      becomes a target of self-restoration of cancer stem cell by means of immune
      surveillance. A human monoclonal antibody, CLN-IgG recognizes vimentin expressing
      on the cell surface of the malignant tumor. Since vimentin network resides in the
      cytoplasm connecting the plasma membrane with chromatin assembly in the nucleus,
      it is highly likely vimentin plays an important role in up-regulation and down
      regulation through signal transduction between certain membrane receptors and
      gene expression with respect to the transformation of the cell. Aberrant
      arrangement of vimentin undergoes malignancy accompanied by epithelial
      mesenchymal-transition relating to the aberrant apoptotic cellular behavior in
      the tumor-niche. Restraint of the aberrant expression of vimentin on the plasma
      membrane of the malignant cell evokes a pertinent signal transduction pathway for
      healing that is an indication there must be a reverse path that reprograms cancer
      stem cells to normal organogenesis.

PMID- 23856244
TI  - Induction of chemokine receptor CXCR4 expression by transforming growth factor
      beta1 in human basal cell carcinoma cells.
AB  - BACKGROUND: Higher CXCR4 expression enhances basal cell carcinoma (BCC) invasion
      and angiogenesis. The underlying mechanism of increased CXCR4 expression in
      invasive BCC is still not well understood. OBJECTIVE: To investigate the
      mechanisms involved in the regulation of CXCR4 expression in invasive BCC.
      METHODS: We used qRT-PCR, RT-PCR, Western blot, and flow cytometric analyses to
      examine different CXCR4 levels among the clinical samples, co-cultured BCC cells
      and BCC cells treated with recombinant transforming growth factor-beta1 (TGF
      beta1) and connective tissue growth factor (CTGF). Immunohistochemical studies
      were used to demonstrate the correlation between TGF-beta1 and CXCR4 expressions.
      The signal transduction pathway and transcriptional regulation were confirmed by
      treatments with chemical inhibitors, neutralizing antibodies, or short
      interfering RNAs, as well as luciferase reporter activity. RESULTS: Invasive BCC
      has higher TGF-beta1 and CTGF levels compared to non-invasive BCC. Non-contact
      dermal fibroblasts co-culture with human BCC cells also increases the expression
      of CXCR4 in BCC cells. Treatment with recombinant human TGF-beta1, but not CTGF,
      enhanced the CXCR4 levels in time- and dose-dependent manners. The protein level
      and surface expression of CXCR4 in human BCC cells was increased by TGF-beta1
      treatment. TGF-beta1 was intensely expressed in the surrounding fibroblasts of
      invasive BCC and was positively correlated with the CXCR4 expression of BCC
      cells. The transcriptional regulation of CXCR4 by TGF-beta1 is mediated by its
      binding to the TGF-beta receptor II and phosphorylation of the extracellular
      signal-related kinase 1/2 (ERK1/2)-ETS-1 pathway. CONCLUSION: TGF-beta1 induces
      upregulation of CXCR4 in human BCC cells by phosphorylation of ERK1/2-ETS-1
      pathway.

PMID- 23856245
TI  - Influence of Salmonella enterica serovar Enteritidis infection on the composition
      of chicken cecal microbiota.
AB  - BACKGROUND: Infection of newly hatched chicks with Salmonella enterica serovar
      Enteritidis (S. Enteritidis) results in an inflammatory response in the
      intestinal tract which may influence the composition of gut microbiota. In this
      study we were therefore interested whether S. Enteritidis induced inflammation
      results in changes in the cecal microbiota. To reach this aim, we compared the
      cecal microbiota of non-infected chickens and those infected by S. Enteritidis by
      pyrosequencing the V3/V4 variable regions of genes coding for 16S rRNA. RESULTS:
      Cecal microbiota of chickens up to 19 days of life was dominated by
      representatives of Enterobacteriaceae, Lachnospiraceae and Ruminococcaceae,
      followed by Lactobacillaceae. The presence of Lachnospiraceae did not change
      after S. Enteritidis infection. Enterobacteriaceae increased and Ruminococcaceae
      decreased after S. Enteritidis infection in two independent experiments although
      these results were not significant. A significant increase in both experiments
      was observed only for the representatives of Lactobacillaceae which may correlate
      with their microaerophilic growth characteristic compared to the obligate
      anaerobes from the families Lachnospiraceae and Ruminococcaceae. CONCLUSIONS: We
      conclude that S. Enteritidis infection influences the composition of the cecal
      microbiota in chickens but these changes are minor in nature and should be
      understood more as an indirect consequence of infection and inflammation rather
      than a positively selected evolutionary trait.

PMID- 23856246
TI  - The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems
      pharmacology.
AB  - The NCI-60 cell lines are the most frequently studied human tumor cell lines in
      cancer research. This panel has generated the most extensive cancer pharmacology
      database worldwide. In addition, these cell lines have been intensely
      investigated, providing a unique platform for hypothesis-driven research focused
      on enhancing our understanding of tumor biology. Here, we report a comprehensive
      analysis of coding variants in the NCI-60 panel of cell lines identified by whole
      exome sequencing, providing a list of possible cancer specific variants for the
      community. Furthermore, we identify pharmacogenomic correlations between specific
      variants in genes such as TP53, BRAF, ERBBs, and ATAD5 and anticancer agents such
      as nutlin, vemurafenib, erlotinib, and bleomycin showing one of many ways the
      data could be used to validate and generate novel hypotheses for further
      investigation. As new cancer genes are identified through large-scale sequencing
      studies, the data presented here for the NCI-60 will be an invaluable resource
      for identifying cell lines with mutations in such genes for hypothesis-driven
      research. To enhance the utility of the data for the greater research community,
      the genomic variants are freely available in different formats and from multiple
      sources including the CellMiner and Ingenuity websites.

PMID- 23856247
TI  - miR-205 targets PTEN and PHLPP2 to augment AKT signaling and drive malignant
      phenotypes in non-small cell lung cancer.
AB  - AKT signaling is constitutively activated in various cancers, due in large part
      to loss-of-function in the PTEN and PHLPP phosphatases that act as tumor
      suppressor genes. However, AKT signaling is activated widely in non-small cell
      lung cancers (NSCLC) where genetic alterations in PTEN or PHLPP genes are rare,
      suggesting an undefined mechanism(s) for their suppression. In this study, we
      report upregulation of the oncomir microRNA (miR)-205 in multiple subtypes of
      NSCLC, which directly represses PTEN and PHLPP2 expression and activates both the
      AKT/FOXO3a and AKT/mTOR signaling pathways. miR-205 overexpression in NSCLC cells
      accelerated tumor cell proliferation and promoted blood vessel formation in vitro
      and in vivo. Conversely, RNA interference-mediated silencing of endogenous miR
      205 abrogated these effects. The malignant properties induced by miR-205 in NSCLC
      cells were reversed by AKT inhibitors, FOXO3a overexpression, rapamycin
      treatment, or restoring PHLPP2 or PTEN expression. Mechanistic investigations
      revealed that miR-205 overexpression was a result of NF-kappaB-mediated
      transactivation of the miR-205 gene. Taken together, our results define a major
      epigenetic mechanism for suppression of PTEN and PHLPP2 in NSCLC, identifying a
      pivotal role for miR-205 in development and progression of this widespread
      disease.

PMID- 23856249
TI  - Fusion-derived epithelial cancer cells express hematopoietic markers and
      contribute to stem cell and migratory phenotype in ovarian carcinoma.
AB  - For a long time, the external milieu of cancer cells was considered to be of
      secondary importance when compared with its intrinsic properties. That has
      changed now as the microenvironment is considered to be a major contributing
      factor toward the progression of tumor. In this study, we show that in human and
      mouse epithelial ovarian carcinoma and mouse lung carcinoma, the interaction
      between tumor-infiltrating hematopoietic cells and epithelial cancer cells
      results in their fusion. Intriguingly, even after the fusion event, cancer cells
      retain the expression of the pan-hematopoietic marker (CD45) and various markers
      of hematopoietic lineage, including those of hematopoietic stem cells, indicating
      that the hematopoietic genome is not completely reprogrammed. This observation
      may have implications on the bone marrow contribution to the cancer stem cell
      population. Interestingly, it was seen that in both cancer models, the expression
      of chemokine receptor CXCR4 was largely contributed to by the fused compartment
      of cancer cells. We hypothesize that the superior migratory potential gained by
      the cancer cells due to the fusion helps in its dissemination to various
      secondary organs upon activation of the CXCR4/CXCL12 axis. We are the first to
      report the presence of a hemato-epithelial cancer compartment, which contributes
      to stem cell markers and CXCR4 in epithelial carcinoma. This finding has
      repercussions on CXCR4-based therapeutics and opens new avenues in discovering
      novel molecular targets against fusion and metastasis.

PMID- 23856248
TI  - PTK6 activation at the membrane regulates epithelial-mesenchymal transition in
      prostate cancer.
AB  - The intracellular tyrosine kinase protein tyrosine kinase 6 (PTK6) lacks a
      membrane-targeting SH4 domain and localizes to the nuclei of normal prostate
      epithelial cells. However, PTK6 translocates from the nucleus to the cytoplasm in
      human prostate tumor cells. Here, we show that while PTK6 is located primarily
      within the cytoplasm, the pool of active PTK6 in prostate cancer cells localizes
      to membranes. Ectopic expression of membrane-targeted active PTK6 promoted
      epithelial-mesenchymal transition in part by enhancing activation of AKT, thereby
      stimulating cancer cell migration and metastases in xenograft models of prostate
      cancer. Conversely, siRNA-mediated silencing of endogenous PTK6 promoted an
      epithelial phenotype and impaired tumor xenograft growth. In mice, PTEN
      deficiency caused endogenous active PTK6 to localize at membranes in association
      with decreased E-cadherin expression. Active PTK6 was detected at membranes in
      some high-grade human prostate tumors, and PTK6 and E-cadherin expression levels
      were inversely correlated in human prostate cancers. In addition, high levels of
      PTK6 expression predicted poor prognosis in patients with prostate cancer. Our
      findings reveal novel functions for PTK6 in the pathophysiology of prostate
      cancer, and they define this kinase as a candidate therapeutic target. Cancer
      Res; 73(17); 5426-37. (c)2013 AACR. 

PMID- 23856250
TI  - Survivin-3B potentiates immune escape in cancer but also inhibits the toxicity of
      cancer chemotherapy.
AB  - Dysregulation in patterns of alternative RNA splicing in cancer cells is emerging
      as a significant factor in cancer pathophysiology. In this study, we investigated
      the little known alternative splice isoform survivin-3B (S-3B) that is
      overexpressed in a tumor-specific manner. Ectopic overexpression of S-3B drove
      tumorigenesis by facilitating immune escape in a manner associated with
      resistance to immune cell toxicity. This resistance was mediated by interaction
      of S-3B with procaspase-8, inhibiting death-inducing signaling complex formation
      in response to Fas/Fas ligand interaction. We found that S-3B overexpression also
      mediated resistance to cancer chemotherapy, in this case through interactions
      with procaspase-6. S-3B binding to procaspase-6 inhibited its activation despite
      mitochondrial depolarization and caspase-3 activation. When combined with
      chemotherapy, S-3B targeting in vivo elicited a nearly eradication of tumors.
      Mechanistic investigations identified a previously unrecognized 7-amino acid
      region as responsible for the procancerous properties of survivin proteins. Taken
      together, our results defined S-3B as an important functional actor in tumor
      formation and treatment resistance.

PMID- 23856251
TI  - Stromally derived lysyl oxidase promotes metastasis of transforming growth factor
      beta-deficient mouse mammary carcinomas.
AB  - The tumor stromal environment can dictate many aspects of tumor progression. A
      complete understanding of factors driving stromal activation and their role in
      tumor metastasis is critical to furthering research with the goal of therapeutic
      intervention. Polyoma middle T-induced mammary carcinomas lacking the type II TGF
      beta receptor (PyMT(mgko)) are highly metastatic compared with control PyMT
      induced carcinomas (PyMT(fl/fl)). We hypothesized that the PyMT(mgko)-activated
      stroma interacts with carcinoma cells to promote invasion and metastasis. We show
      that the extracellular matrix associated with PyMT(mgko) tumors is stiffer and
      has more fibrillar collagen and increased expression of the collagen crosslinking
      enzyme lysyl oxidase (LOX) compared with PyMT(fl/fl) mammary carcinomas.
      Inhibition of LOX activity in PyMT(mgko) mice had no effect on tumor latency and
      size, but significantly decreased tumor metastasis through inhibition of tumor
      cell intravasation. This phenotype was associated with a decrease in keratin 14
      positive myoepithelial cells in PyMT(mgko) tumors following LOX inhibition as
      well as a decrease in focal adhesion formation. Interestingly, the primary source
      of LOX was found to be activated fibroblasts. LOX expression in these fibroblasts
      can be driven by myeloid cell-derived TGF-beta, which is significantly linked to
      human breast cancer. Overall, stromal expansion in PyMT(mgko) tumors is likely
      caused through the modulation of immune cell infiltrates to promote fibroblast
      activation. This feeds back to the epithelium to promote metastasis by modulating
      phenotypic characteristics of basal cells. Our data indicate that epithelial
      induction of microenvironmental changes can play a significant role in
      tumorigenesis and attenuating these changes can inhibit metastasis. Cancer Res;
      73(17); 5336-46. (c)2013 AACR. 

PMID- 23856252
TI  - A low-frequency GLIS3 variant associated with resistance to Japanese type 1
      diabetes.
AB  - The role of low-frequency variants in type 1 diabetes (T1D) susceptibility still
      remains to be clarified. In the present study, we analyzed low-frequency variants
      of the T1D candidate genes in Japanese. We first screened for protein-changing
      variants of 24 T1D candidate genes in 96 T1D patients and 96 control subjects,
      and then the association with T1D was tested in 706 T1D patients and 863 control
      subjects recruited from the collaborating institutions in Japan. In total, 56
      protein-changing variants were discovered; among them, 34 were low-frequency
      variants (allele frequency < 5%). The association analysis of the low-frequency
      variants revealed that only the A908V variant of GLIS3 was strongly associated
      with resistance to T1D (Haldane's odds ratio = 0.046, p = 8.21 * 10(-4), and
      pc=2.22 * 10(-2)). GLIS3 is a zinc finger transcription factor that is highly
      expressed in pancreatic beta cells, and regulates beta cell development and
      insulin gene expression. GLIS3 mRNA is also moderately expressed in the human
      thymus. The precise mechanism responsible for the association is unclear at
      present, but the A908V variant may affect autoimmunity to the GLIS3 protein
      itself; the 908V containing epitope may induce central or peripheral tolerance
      more efficiently than that of 908A.

PMID- 23856253
TI  - A multidisciplinary approach to desmoid tumors. When intra-abdominal fibromatosis
      degenerates into an abscess, which is the right treatment?
AB  - INTRODUCTION: Desmoid tumors are rare benign tumors that originates in the
      fibrous sheath or musculo-aponeurotic structure. Histologically benign, they
      tends to invade locally and to be recurrent. PRESENTATION OF CASE: We report a
      rare case of an intra-abdominal desmoid tumor in a patient affected by familial
      adenomatous polyposis, which degenerated into abscess. Male, 38 years, was
      hospitalized for abdominal pain, bowel obstruction and fever. The computed
      tomography showed a big dishomogeneous mass occupying the whole mesentery with
      internal massive liquefaction. The mass extended from the epigastrium for 13cm up
      to L3. On the right mesogastric side a solid, thick mass of about 2cm, with a
      length of 4.5cm, was identified; it was not cleavable from the wall and from some
      of the loops. We decided to perform a computed tomography-guided percutaneous
      drainage. Two hundred ml of purulent necrotic material was aspirated, and washing
      with antibiotic solution was carried out. Cytological examination of fluid
      drainage showed histiocytes and neutrophils. At follow-up, the patient's clinical
      condition had improved. An abdominal ultrasound showed a substantial reduction in
      the diameter of the mass. DISCUSSION: Diagnosis and treatment of desmoids tumor
      in patients with familial adenomatous polyposis may be difficult, especially when
      desmoids are located intra-abdominally and in the mesentery. Seldom will desmoid
      tumors be complicated by abscess formation. CONCLUSION: The management of
      desmoids tumors is not easy and the choice of the best treatment may be difficult
      due to the different possible anatomical presentations.

PMID- 23856255
TI  - Angiosarcoma of the spleen presenting as spontaneous splenic rupture: A rare case
      report and review of the literature.
AB  - INTRODUCTION: Angiosarcoma of the spleen is a rare malignancy of vascular origin
      with a high rate of metastasis and poor prognosis. We report one such rare case
      of spontaneous splenic rupture, along with a review of current literature.
      PRESENTATION OF CASE: A 30 year old man presented to our emergency services with
      severe abdominal pain, distension, hypotension and splenomegaly. Investigations
      revealed a marked anaemia, coagulopathy, severe lactic acidosis, and acute kidney
      injury. Imaging demonstrated splenomegaly with acute haemorrhage and
      lymphadenopathy. Laparotomy and splenectomy revealed piecemeal spleen and nodular
      omentum. The patient suffered an intra-operative cardiorespiratory arrest, and
      despite successful resuscitation, fatally arrested postoperatively in ICU.
      Histology revealed a primary splenic angiosarcoma with omental metastases.
      DISCUSSION: Primary splenic angiosarcoma was first reported in 1879, with only
      200 cases reported to date, largely as isolated case reports, with an annual
      incidence of 0.14-0.25 per million. With variable symptomatology and a potential
      to present with life-threatening complications, early diagnosis is paramount. CT
      scanning shows distinctive changes and is invaluable in disease assessment.
      Tissue diagnosis is often possible only after splenectomy. Spontaneous rupture
      carries the worst prognosis. CONCLUSION: Primary splenic angiosarcoma is a rare
      and aggressive malignancy that often presents with metastatic disease, and
      largely carries a dismal prognosis. Definitive diagnosis is challenging, but
      imaging with CT scanning can show characteristic changes and establish any
      metastatic disease. With no established adjuvant therapy long term outlook
      remains poor even if treated successfully by surgery.

PMID- 23856254
TI  - Upper gastrointestinal bleeding: A rare complication of acute cholecystitis.
AB  - INTRODUCTION: Haemobilia is a rare complication of acute cholecystitis and may
      present as upper gastrointestinal bleeding. PRESENTATION OF CASE: We describe two
      patients with acute cholecystitis presenting with upper gastrointestinal bleeding
      due to haemobilia. Bleeding from the duodenal papilla was seen at endoscopy in
      one case but none in the other. CT demonstrated acute cholecystitis with a
      pseudoaneurysm of the cystic artery in both cases. Definitive control of
      intracholecystic bleeding was achieved in both cases by embolisation of the
      cystic artery. Both patients remain symptom free. One had subsequent laparoscopic
      cholecystostomy and the other no surgery. DISCUSSION: Pseudoaneurysms of the
      cystic artery are uncommon in the setting of acute cholecystitis. OGD and CT
      angiography play a key role in diagnosis. Transarterial embolisation (TAE) is
      effective in controlling bleeding. TAE followed by interval cholecystectomy
      remains the treatment of choice in surgically fit patients. CONCLUSION: We
      highlight an unusual cause of upper GI haemorrhage. Surgeons need to be aware of
      this rare complication of acute cholecystitis. Immediate non-surgical management
      in these cases proved to be safe and effective.

PMID- 23856256
TI  - Post-intravesical BCG epididymo-orchitis: Case report and a review of the
      literature.
AB  - INTRODUCTION: Bladder cancer is a significant epidemiological disease. It is
      managed by primary resection and on-going surveillance for recurrent disease.
      Intravesical BCG therapy is used in superficial carcinomas to lower the incidence
      of recurrence and prolong the time to recurrence. BCG therapy is not without its
      rare but serious side effects. PRESENTATION OF CASE: A 75-year-old man presented
      to the urologist with right testicular pain, after four previous TURBT
      operations, two courses of intravesical BCG therapy and one STAT dose of
      intravesical mitomycin. The patient's USS testis showed hypoechoic lesions in the
      right testis. An orchiectomy was carried out due to the possibility of the USS
      showing a malignancy. Histology confirmed BCG epididymo-orchitis. DISCUSSION:
      This patient presented with testicular pain fifteen months after the cessation of
      BCG therapy. Clinicians need to be aware of the potentially long dormancy periods
      for BCG infections, and their complications, as well as the acute infective BCG
      presentations. The literature is reviewed and shows the wide range of infective
      BCG presentations from acute disseminated sepsis to insidious focal infections
      such as parotiditis and discitis. CONCLUSION: This case report demonstrates that
      due to the delayed and gradual onset of symptoms, BCG infections are difficult to
      diagnose. The report and the review remind surgeons to keep BCG infection amongst
      their differentials when treating patients who present after BCG therapy.

PMID- 23856258
TI  - "The role of the calcium sensing receptor (CaSR) in health and disease,
      implications for translational medicine" or the multifaceted CaSR: a Training
      Network for young scientists.

PMID- 23856257
TI  - Coronin 1 is dispensable for leukocyte recruitment and liver injury in
      concanavalin A-induced hepatitis.
AB  - Coronin 1, a member of the evolutionary conserved coronin protein family, is
      highly expressed in all leukocytes. In mice and human, genetic inactivation of
      coronin 1 results in immuno-deficiencies that are linked to a strong reduction of
      naive T cell numbers in peripheral organs, while memory/effector T cells, B
      cells, monocytes and neutrophils are less or not at all affected. Whether or not
      coronin 1 is important for leukocyte functions such as migration and phagocytosis
      has been a matter of debate. The current work addresses coronin 1-dependent
      leukocyte function by analyzing the response of coronin 1-deficient mice in a
      model of concanavalin A (Con A)-induced liver injury. Histological evaluation and
      determination of serum liver enzyme levels showed that coronin 1-deficient mice
      develop signs of acute hepatitis similar to Con A-treated wild type mice despite
      a reduced activation of T cells in the absence of coronin 1. Furthermore,
      analysis by intravital microscopy following Con A stimulation revealed that Gr-1+
      neutrophils and CD4+ T cell adhesion in the post-sinusoidal venules increased in
      wild type as well as in coronin 1-deficient mice. These results suggest that
      coronin 1, while important for naive T cell survival, is dispensable for other
      leukocyte function under inflammatory conditions in vivo.

PMID- 23856259
TI  - Preface.

PMID- 23856260
TI  - The CASR gene: alternative splicing and transcriptional control, and calcium
      sensing receptor (CaSR) protein: structure and ligand binding sites.
AB  - The calcium-sensing receptor (CaSR) is a G protein-coupled receptor encoded by a
      single copy gene. The human CASR gene spans ~103-kb and has eight exons.
      Promoters P1 and P2 drive transcription of exons 1A and 1B, respectively,
      encoding alternative 5'-UTRs that splice to exon 2 encoding the common part of
      the 5'-UTR. Exons 2-7 encode the CaSR protein of 1078 amino acids. Functional
      elements responsive to 1,25-dihydroxyvitamin D, proinflammatory cytokines, and
      glial cells missing-2 are present in the CASR promoters. Evolutionarily, the exon
      structure, first seen in aquatic vertebrates, is well-conserved with a single
      linkage disequilibrium haplotype block for protein coding exons 2-7. Structural
      features of the human CaSR protein are: an N-terminal signal peptide (19 amino
      acids (aa)); an extracellular domain (~600 aa) having a bi-lobed Venus Flytrap
      (VFT) domain with several Ca(2+)-binding sites; and a nine-cysteines domain that
      transduces the activation signal to the 7-transmembrane domain (250 aa) and the C
      terminal tail (216 aa).

PMID- 23856261
TI  - The calcium sensing receptor life cycle: trafficking, cell surface expression,
      and degradation.
AB  - The calcium-sensing receptor (CaSR) must function in the chronic presence of
      agonist, and recent studies suggest that its ability to signal under such
      conditions depends upon the unique mechanism(s) regulating its cellular
      trafficking. This chapter will highlight the evidence supporting an intracellular
      endoplasmic reticulum-localized pool of CaSR that can be mobilized to the plasma
      membrane by CaSR signaling, leading to agonist-driven insertional signaling
      (ADIS). I summarize evidence for the role of small GTP binding proteins (Rabs,
      Sar1 and ARFs), cargo receptors or chaperones (p24A, RAMPs) and interacting
      proteins (14-3-3 proteins, calmodulin) in anterograde trafficking of CaSR, and
      discuss the potential signaling specializations arising from CaSR interactions
      with caveolins or Filamin A/Rho. Finally, I summarize current knowledge about
      CaSR endocytosis and degradation by both the proteasome and lysosome, and
      highlight recent studies indicating that defective trafficking of CaSR or
      interacting protein mutants contributes to pathology in disorders of calcium
      homeostasis. 

PMID- 23856262
TI  - Calcium-sensing receptor (CaSR): pharmacological properties and signaling
      pathways.
AB  - In this article we consider the mechanisms by which the calcium-sensing receptor
      (CaSR) induces its cellular responses via the control (activation or inhibition)
      of signaling pathways. We consider key features of CaSR-mediated signaling
      including its control of the heterotrimeric G-proteins Gq/11, Gi/o and G12/13 and
      the downstream consequences recognizing that very few CaSR-mediated cell
      phenomena have been fully described. We also consider the manner in which the
      CaSR contributes to the formation of specific signaling scaffolds via peptide
      recognition sequences in its intracellular C-terminal along with the origins of
      its high level of cooperativity, particularly for Ca(2+)o, and its remarkable
      resistance to desensitization. We also consider the nature of the mechanisms by
      which the CaSR controls oscillatory and sustained Ca(2+)i mobilizing responses
      and inhibits or elevates cyclic adenosine monophosphate (cAMP) levels dependent
      on the cellular and signaling context. Finally, we consider the diversity of the
      receptor's ligands, ligand binding sites and broader compartment-dependent
      physiological roles leading to the identification of pronounced ligand-biased
      signaling for agonists including Sr(2+) and modulators including l-amino acids
      and the clinically effective calcimimetic cinacalcet. We note the implications of
      these findings for the development of new designer drugs that might target the
      CaSR in pathophysiological contexts beyond those established for the treatment of
      disorders of calcium metabolism. 

PMID- 23856263
TI  - Role of the calcium-sensing receptor in extracellular calcium homeostasis.
AB  - Maintaining a constant level of blood Ca(2+) is essential because of calcium's
      myriad intracellular and extracellular roles. The CaSR plays key roles in
      maintaining [Formula: see text] homeostasis by detecting small changes in blood
      Ca(2+) and modulating the production/secretion of the Ca(2+)-regulating hormones,
      PTH, CT, FGF23 and 1,25(OH)2D3, so as to appropriately regulate Ca(2+) transport
      into or out of blood via kidney, intestine, and/or bone. When Ca(2+) is high, the
      CaSR suppresses PTH synthesis and secretion, promotes its degradation, and
      inhibits parathyroid cellular proliferation. It has just the opposite effects on
      the C-cell, stimulating CT when [Formula: see text] is high. In bone, Ca(2+),
      acting via the CaSR, stimulates recruitment and proliferation of preosteoblasts,
      their differentiation to mature osteoblasts, and synthesis and mineralization of
      bone proteins. Conversely, [Formula: see text] inhibits the formation and
      activity and promotes apoptosis of osteoclasts, likely via the CaSR. These
      actions tend to mobilize skeletal Ca(2+) during [Formula: see text] deficiency
      and retain it when Ca(2+) is plentiful. 

PMID- 23856265
TI  - Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte
      and water metabolism.
AB  - The extracellular calcium-sensing receptor (CaSR) is a family C G-protein-coupled
      receptor (GPCR) that is expressed at multiple sites, including the parathyroids
      and kidneys. The human CASR gene, located on chromosome 3q21.1, encodes a 1078
      amino acid protein. More than 230 different disease-causing mutations of the CaSR
      have been reported. Loss-of-function mutations lead to three hypercalcemic
      disorders, which are familial hypocalciuric hypercalcemia (FHH), neonatal severe
      hyperparathyroidism and primary hyperparathyroidism. Gain-of-function mutations,
      on the other hand, result in the hypocalcemic disorders of autosomal dominant
      hypocalcemia and Bartter syndrome type V. Moreover, autoantibodies directed
      against the extracellular domain of the CaSR have been found to be associated
      with FHH in some patients, and also in some patients with hypoparathyroidism that
      may be part of autoimmune polyglandular syndrome type 1. Studies of disease
      causing CASR mutations have provided insights into structure-function
      relationships and highlighted intra-molecular domains that are critical for
      ligand binding, intracellular signaling, and receptor trafficking. 

PMID- 23856264
TI  - Control of renal calcium, phosphate, electrolyte, and water excretion by the
      calcium-sensing receptor.
AB  - Through regulation of excretion, the kidney shares responsibility for the
      metabolic balance of calcium (Ca(2+)) with several other tissues including the GI
      tract and bone. The balances of Ca(2+) and phosphate (PO4), magnesium (Mg(2+)),
      sodium (Na(+)), potassium (K(+)), chloride (Cl(-)), and water (H2O) are linked
      via regulatory systems with overlapping effects and are also controlled by
      systems specific to each of them. Cloning of the calcium-sensing receptor (CaSR)
      along with the recognition that mutations in the CaSR gene are responsible for
      two familial syndromes characterized by abnormalities in the regulation of PTH
      secretion and Ca(2+) metabolism (Familial Hypocalciuric Hypercalcemia, FHH, and
      Autosomal Dominant Hypocalcemia, ADH) made it clear that extracellular Ca(2+)
      (Ca(2+)o) participates in its own regulation via a specific, receptor-mediated
      mechanism. Demonstration that the CaSR is expressed in the kidney as well as the
      parathyroid glands combined with more complete characterizations of FHH and ADH
      established that the effects of elevated Ca(2+) on the kidney (wasting of Na(+),
      K(+), Cl(-), Ca(2+), Mg(2+) and H2O) are attributable to activation of the CaSR.
      The advent of positive and negative allosteric modulators of the CaSR along with
      mouse models with global or tissue-selective deletion of the CaSR in the kidney
      have allowed a better understanding of the functions of the CaSR in various
      nephron segments. The biology of the CaSR is more complicated than originally
      thought and difficult to define precisely owing to the limitations of reagents
      such as anti-CaSR antibodies and the difficulties inherent in separating direct
      effects of Ca(2+) on the kidney mediated by the CaSR from associated CaSR-induced
      changes in PTH. Nevertheless, renal CaSRs have nephron-specific effects that
      contribute to regulating Ca(2+) in the circulation and urine in a manner that
      assures a narrow range of Ca(2+)o in the blood and avoids excessively high
      concentrations of Ca(2+) in the urine. 

PMID- 23856266
TI  - Calcimimetic and calcilytic drugs for treating bone and mineral-related
      disorders.
AB  - The calcium-sensing receptor (CaSR) plays a pivotal role in regulating systemic
      Ca(2+) homeostasis and is a target for drugs designed to treat certain disorders
      of bone and mineral metabolism. Calcimimetics are agonists or positive allosteric
      modulators of the CaSR; they inhibit parathyroid hormone (PTH) secretion and
      stimulate renal Ca(2+) excretion. The first calcimimetic drug is cinacalcet, a
      positive allosteric modulator of the CaSR that is approved for treating secondary
      hyperparathyroidism (HPT) in patients on renal replacement therapy and for some
      forms of primary HPT characterized by clinically significant hypercalcemia.
      Cinacalcet is also being investigated as a therapy for other hypercalcemic
      conditions and certain hypophosphatemic disorders. Calcilytics are CaSR
      inhibitors that stimulate the secretion of PTH and decrease renal excretion of
      Ca(2+). Although calcilytics have failed thus far as anabolic therapies for
      osteoporosis, they are currently being evaluated as novel therapies for new
      indications involving hypocalcemia and/or hypercalciuria. 

PMID- 23856267
TI  - CaSR function in the intestine: Hormone secretion, electrolyte absorption and
      secretion, paracrine non-canonical Wnt signaling and colonic crypt cell
      proliferation.
AB  - Expression and function of the CaSR have been shown in some mammalian taste buds
      and basal cells of the esophagus. Signaling cascades responsible for CaSR
      mediated stimulation of H(+)-K(+)-ATPase on human parietal cells have been
      defined. Transgenic mice and reductionistic cell culture models have shown that
      the CaSR promotes gastrin secretion from G cells, cholecystokinin (CCK) secretion
      from duodenal I cells and BMP-2 secretion from sub-epithelial myofibroblasts. In
      addition, the CaSR mediates a novel paracrine relationship between myofibroblasts
      and overlying epithelial cells in the colon. Thus, CaSR activators stimulate
      secretion of Wnt5a from myofibroblasts and expression of the Wnt5a receptor Ror2
      in epithelial cells. CaSR-mediated Wnt5a/Ror2 engagement stimulates epithelial
      differentiation and reduces expression of the receptor for tumor necrosis factor
      (TNFR1). CaSR activators also modulate intestinal motility, inhibit Cl(-)
      secretion and stimulate Na(+) absorption in both the small intestine and colon.
      Colonic epithelia from conditional and global CaSR knockout mice exhibit
      increased proliferation with increased Wnt/beta-catenin signaling, demonstrating
      that the CaSR negatively modulates colonic epithelial growth. 

PMID- 23856268
TI  - The calcium-sensing receptor in the breast.
AB  - Normal breast epithelial cells and breast cancer cells express the calcium
      sensing receptor (CaSR), the master regulator of systemic calcium metabolism.
      During lactation, activation of the CaSR in mammary epithelial cells
      downregulates parathyroid hormone-related protein (PTHrP) levels in milk and in
      the circulation, and increases calcium transport into milk. In contrast, in
      breast cancer cells the CaSR upregulates PTHrP production. A switch in G-protein
      usage underlies the opposing effects of the CaSR on PTHrP expression in normal
      and malignant breast cells. During lactation, the CaSR in normal breast cells
      coordinates a feedback loop that matches the transport of calcium into milk and
      maternal calcium metabolism to the supply of calcium. A switch in CaSR G-protein
      usage during malignant transformation converts this feedback loop into a feed
      forward cycle in breast cancer cells that may promote the growth of osteolytic
      skeletal metastases. 

PMID- 23856270
TI  - Roles of the calcium sensing receptor in the central nervous system.
AB  - The calcium sensing receptor (CaSR) is expressed by subpopulations of neuronal
      and glial cells throughout the brain and is activated by extracellular calcium
      [Formula: see text] . During development, the CaSR regulates neuronal cell growth
      and migration as well as oligodendroglial maturation and function. Emerging
      evidence suggests that in nerve terminals, CaSR is implicated in synaptic
      plasticity and neurotransmission. In this review, we analyze the roles attributed
      to CaSR in regulating diverse brain functions, including central regulation of
      body fluid composition and blood pressure. We also discuss the potential
      relevance of Ca(2+)-sensing in brain by other family C G protein-coupled
      receptors. Finally, evidence that the CaSR contributes to the pathogenesis of
      various brain disorders raises the possibility that pharmacological modulators of
      the CaSR may have therapeutic benefit. 

PMID- 23856269
TI  - Role of the calcium-sensing receptor in calcium regulation of epidermal
      differentiation and function.
AB  - The epidermis is a stratified squamous epithelium composed of proliferating basal
      and differentiated suprabasal keratinocytes. It serves as the body's major
      physical and chemical barrier against infection and harsh environmental insults,
      as well as preventing excess water loss from the body into the atmosphere.
      Calcium is a key regulator of the proliferation and differentiation in
      keratinocytes. Elevated extracellular Ca(2+) concentration ([Ca(2+)]o) raises the
      levels of intracellular free calcium ([Ca(2+)]i), promotes cell-cell adhesion,
      and activates differentiation-related genes. Keratinocytes deficient in the
      calcium-sensing receptor fail to respond to [Ca(2+)]o stimulation and to
      differentiate, indicating a role for the calcium-sensing receptor in transducing
      the [Ca(2+)]o signal during differentiation. The concepts derived from in vitro
      gene knockdown experiments have been evaluated and confirmed in three mouse
      models in vivo. 

PMID- 23856271
TI  - The extracellular calcium-sensing receptor, CaSR, in fetal development.
AB  - In fetal mammals, serum levels of both total and ionized calcium significantly
      exceed those in the adult. This relative fetal hypercalcemia is crucial for
      skeletal development and is maintained irrespectively of maternal serum calcium
      levels. Elegant studies by Kovacs and Kronenberg have previously addressed the
      role of the CaSR in creating and maintaining this relative fetal hypercalcemia,
      through the regulation of parathyroid hormone-related peptide secretion. More
      recently we have shown that the CaSR is widely distributed throughout the
      developing fetus, where the receptor plays major, unexpected roles in ensuring
      growth and maturation of several organs. In this article, we present evidence for
      a role of the CaSR in the control of skeletal development, and how fetal
      hypercalcemia, acting through the CaSR, regulates lung development. 

PMID- 23856272
TI  - Role of calcium sensing receptor (CaSR) in tumorigenesis.
AB  - The extracellular Ca(2+)-sensing receptor (CaSR) is a robust promoter of
      differentiation in colonic epithelial cells and functions as a tumor suppressor
      in colon cancer. CaSR mediates its biologic effects through diverse mechanisms.
      Loss of CaSR expression activates a myriad of stem cell-like molecular features
      that drive and sustain the malignant and drug-resistant phenotypes of colon
      cancer. This CaSR-null phenotype, however, is not irreversible and induction of
      CaSR expression in CaSR-null cells promotes cell death mechanisms and restores
      drug sensitivity. The CaSR also functions as a tumor suppressor in breast cancer
      and promotes cellular sensitivity to cytotoxic drugs. BRCA1 and CaSR functions
      intersect in breast cancer cells, and CaSR activation can rescue breast cancer
      cells from the deleterious effect of BRCA1 mutations. 

PMID- 23856273
TI  - Intraosseous leiomyosarcoma arising in the epiphysis of the distal femur.
AB  - Herein, we present a rare case of intraosseous leiomyosarcoma arising in the
      epiphysis of the distal femur and showing unusual radiographic features. A 44
      year-old man presented with a pain in the left knee joint. Computed tomography
      revealed an intraosseous lesion with slightly increased attenuation and a thin
      marginal sclerotic rim in the femoral medial condyle. The signal of the lesion
      was hypointense on T1-weighted magnetic resonance (MR) images and hyperintense on
      fat-suppressed T2-weighted MR images. After gadolinium administration, the signal
      of the lesion was moderately and diffusely enhanced. The histological diagnosis
      of leiomyosarcoma was made based on a preoperative core biopsy specimen.
      Microscopic examination of the resected specimen revealed an ill-defined
      intraosseous tumor composed of proliferated atypical and mildly pleomorphic
      smooth muscle cells permeating among the bone trabeculae with only focal
      destruction of the bone trabeculae and low mitotic activity, indicating low grade
      leiomyosarcoma. The bone trabeculae at the periphery of the tumor were mildly
      thickened and anastomosed with a rim of an increased number of osteoblasts.
      Systemic examination showed no tumorous lesions in other anatomical sites.
      Leiomyosarcomas rarely present in the bone as a diffuse intertrabecular growth,
      even in low grade tumors. 

PMID- 23856274
TI  - Colonized Aedes albopictus and its sexual performance in the wild: implications
      for SIT technology and containment.
AB  - BACKGROUND: Mating is a physiological process of crucial importance underlying
      the size and maintenance of mosquito populations. In sterile and incompatible
      insect technologies (SIT and IIT), mating is essential for mass production,
      persistence, and success of released individuals, and is a central parameter for
      judging the effectiveness of SIT/IIT programs. Some mosquitoes have an enormous
      reproductive potential for both themselves and pathogens and mating may
      contribute to persistence of infection in nature. As Aedes albopictus can
      transmit flaviviruses both sexually and horizontally, and as infected insects are
      usually derived from laboratory colonies, we investigated the implications of
      mating between a long-term laboratory colony of Ae. albopictus and wild
      populations. METHODS: Through a series of mating experiments, we examined the
      reproductive outcomes of sexual cross-affinity between laboratory-raised and wild
      adults of Ae. albopictus. RESULTS: The results indicated appreciable mating
      compatibility between laboratory-reared and wild adults, and equivalent levels of
      egg production among reciprocal crosses. We also observed comparable larval
      eclosion in lab females mated with wild males, and increased adult longevity in
      female offspring from wild females|*|laboratory males crosses. CONCLUSIONS: Taken
      together, these data suggest that Ae. albopictus can preserve its reproductive
      fitness over a long period of time in the laboratory environment and has valuable
      attributes for SIT application. These observations together with the ability to
      successfully inseminate heterospecific females indicate the potential of Ae.
      albopictus to act as an ecological barrier if non-sterilized males are massively
      released in areas occupied by Aedes aegypti. The observed substantial
      reproductive fitness combined with the capability to reproduce both, itself and
      viruses illustrates the potential of Ae. albopictus to pose a serious threat if
      infected and released accidentally.

PMID- 23856276
TI  - Chinese plasma-derived products supply under the lot release management system in
      2007-2011.
AB  - In 2007, the Chinese State Food and Drug Administration (SFDA) implemented a
      management system for lot release of all plasma-derived products. Since then,
      there have been only a few systematic studies of the blood supply, which is a
      concern when considering the small amount of plasma collected per capita
      (approximately 3 L/1000 people). As a result, there may be a threat to the safety
      of the available blood supply. In this study, we examined the characteristics of
      the supply of Chinese plasma-derived products. We investigated the reports of lot
      released biological products derived from all 8 national or regional regulatory
      authorities in China from 2007 to 2011. The market supply characteristics of
      Chinese plasma-derived products were analyzed by reviewing the changes in supply
      varieties, the batches of lot-released plasma-derived products and the actual
      supply. As a result, the national regulatory authorities can more accurately
      develop a specific understanding of the production and quality management
      information provided by Chinese plasma product manufacturers. The implementation
      of the lot release system further ensures the clinical validity of the plasma
      derived products in China and improves the safety of using plasma-derived
      products. This work provides an assessment of the future Chinese market supply of
      plasma-derived products and can function as a theoretical basis for the
      establishment of hemovigilance.

PMID- 23856275
TI  - Obesity and the risk of late mortality after aortic valve replacement with small
      prosthesis.
AB  - BACKGROUND: Whether obesity is related to late mortality with implantation of
      small aortic prosthesis remains to be clarified. This study was aimed to evaluate
      the effect of obesity on late survival of patients after aortic valve replacement
      (AVR) with implantation of small aortic prosthesis (size <= 21 mm). METHODS: From
      January 1998 to December 2008, 307 patients in our institution who underwent
      primary AVR with smaller prostheses survived the 30 days after surgery. Patients
      were defined as normal if body mass index (BMI) was < 24 kg/m2, as overweight if
      BMI 24-27.9 kg/m2, and as obese if BMI >= 28 kg/m2. Data of New York Heart
      Association (NYHA) functional classification, left ventricular ejection fraction
      (LVEF), effective orifice area index (EOAI), and left ventricular mass index
      (LVMI) of the patients collected at the 3rd month (M), 6th M, 1st year (Y), 3rd
      Y, 5th Y, 8th Y after operation respectively. RESULTS: By multivariable analysis,
      obesity was an independent factor of late mortality (hazard ratio [HR]: 1.62; P =
      0.01). The obesity and overweight group had more poor survival (p < 0.001) and
      higher proportion of NYHA class III/IV (p < 0.01) compared with the normal group.
      Lower EOAI and higher LVMI were found in obesity and overweight group, but we saw
      no significant difference about LVEF among the three groups. CONCLUSIONS: Obesity
      was associated with increased late mortality of patients after AVR with
      implantation of small aortic prosthesis. Being obese or and overweight may also
      affect the NYHA classification, even in the longer term. EOAI should be improved
      where possible, as it may reduce late mortality and improve quality of life in
      obese or overweight patients.

PMID- 23856277
TI  - Ultrasound in rheumatology: where are we and where are we going?
AB  - OBJECTIVE: To know rheumatologists' opinion on the usefulness of ultrasound in
      diagnostic and therapeutic decision making as applied to rheumatic diseases.
      MATERIAL AND METHODS: A National survey was sent to all rheumatology units in
      hospitals with at least 200 beds. The questionnaire included: a) general data, b)
      purpose and most common areas of ultrasound exploration and c) assessment of the
      usefulness of ultrasound in routine clinical practice in general and in some
      rheumatologic diseases. RESULTS: One-hundred-sixty-nine out of 234 rheumatology
      units contacted answered the questionnaire. The utility in routine clinical
      practice was scored at 7.8 (scale 0-10) and ultrasound was integrated in making
      diagnostic and therapeutic decisions. Half of the indications (50.9%) were
      ultrasound related to the process of diagnosis of diseases or treatment decision
      making (monitoring synovitis 14.6%, guided puncture 11.4%, early detection of
      joint erosion or synovitis 10.3%, early detection of enthesopathy 5.9%, carpal
      tunnel syndrome or other peripheral neuropathies 3.4%, detection of uric acid or
      pyrophosphate deposits 3%, vasculitis 1% and others 1.1%. On a 1-5 Likert, scale
      most of the answers support the use of ultrasound in clinical practice,
      especially in diagnostic and therapeutic decision making for detection of
      subclinical synovitis, erosions and treatment decisions in rheumatoid arthritis,
      enthesitis diagnosis, crystal diseases, polymyalgia rheumatica and giant cell
      arteritis. CONCLUSIONS: Ultrasound is becoming a useful tool integrated into
      clinical practice and is linked to the decision making processes in the areas of
      diagnosis, activity and treatment.

PMID- 23856278
TI  - Oxidative stress and lowered total antioxidant status are associated with a
      history of suicide attempts.
AB  - BACKGROUND: There is evidence that depression is accompanied by inflammation,
      oxidative and nitrosative stress (O&NS) and metabolic disorders. However links
      between oxidative stress and suicide attempts in depressed patients are poorly
      understood. This study examines whether a history of suicide attempts is
      associated with inflammation, O&NS and metabolic disorders. METHODS: Blood
      specimens were collected from study participants aged 18-60 (N=342) recruited at
      the State University of Londrina, Brazil, and measured for oxidative stress
      biomarkers: nitric oxide metabolites (NOx), lipid hydroperoxides,
      malondialdehyde, advanced oxidation protein products and plasma total antioxidant
      potential (TRAP); inflammatory biomarkers: fibrinogen, high-sensitivity C
      reactive protein, erythrocyte sedimentation rate, interleukin-6 and tumor
      necrosis factor-alpha; and metabolic variables. Subjects were divided into those
      with (n=141) and without (n=201) a history of suicidal attempts. RESULTS:
      Individuals with a history of suicide attempts had significantly higher levels of
      NOx and lipid hydroperoxides and lowered TRAP as compared to individuals without
      suicide attempts. There were no significant associations between a history of
      suicide attempts and inflammatory and metabolic biomarkers and metabolic
      syndrome. Logistic regression showed that both unipolar and bipolar disorder,
      female gender, smoking behavior and lipid hydroperoxides were significantly
      associated with a history of suicide attempts. The combined effects of oxidative
      stress, smoking, depression, female gender were independent from classical risk
      factors, including marital status, years of education and anxiety. CONCLUSIONS:
      O&NS as well as lowered antioxidant levels may play a role in the pathophysiology
      of suicidal behavior independently from the effects of depression and smoking,
      both of which are associated with increased O&NS, and classical suicide
      predictors, such as years of education and marital status.

PMID- 23856279
TI  - Copeptin during rest and exercise in major depression.
AB  - BACKGROUND: High vasopressin levels and a correlation between vasopressin and
      cortisol has been observed in patients with depression. The aim was to assess
      copeptin, the c-terminal of provasopressin, and the association between cortisol,
      adrenocorticotropic hormone (ACTH) and copeptin in patients with depression.
      Secondly, to examine the copeptin response to acute exercise and aerobic
      training. METHODS: Copeptin, ACTH, and cortisol were measured in 111 patients
      with depression and 57 controls at rest. Copeptin was also measured during
      exercise. The depressed patients were subsequently randomized to an aerobic
      training intervention or an exercise control intervention. RESULTS: The plasma
      level of copeptin in depressed subjects was 5.14 pg/ml (IQR 3.4-8.4) and 4.82
      pg/ml (IQR 2.8-7.5) in healthy controls (p=.66). The association between copeptin
      and cortisol was.02 (95% CI -.44 to.48; p=.93) and the association between
      copeptin and ACTH was -.06 (95% CI -.17 to.05; p=.27). All associations were
      independent of depression status (p=.15). Aerobic exercise training did not
      influence copeptin levels at rest (p=.09) or the response to acute exercise
      (p=.574). Copeptin decreased at rest in response to aerobic training in
      participants with high compliance to the exercise intervention (p=.04).
      LIMITATIONS: We did not measure plasma osmolality, which is a possible confounder
      in this study. CONCLUSIONS: Copeptin levels are not elevated or associated to
      ACTH or cortisol in depressed patients. Aerobic exercise training decreased
      copeptin levels in high attenders only. This study does not support a role of
      copeptin or vasopressin in depression.

PMID- 23856280
TI  - The neural correlates of reward-related processing in major depressive disorder:
      a meta-analysis of functional magnetic resonance imaging studies.
AB  - BACKGROUND: A growing number of functional magnetic resonance imaging (fMRI)
      studies have been conducted in major depressive disorder (MDD) to elucidate
      reward-related brain functions. The aim of this meta-analysis was to examine the
      common reward network in the MDD brain and to further distinguish the brain
      activation patterns between positive stimuli and monetary rewards as well as
      reward anticipation and outcome. METHODS: A series of activation likelihood
      estimation (ALE) meta-analyses were performed across 22 fMRI studies that
      examined reward-related processing, with a total of 341 MDD patients and 367
      healthy controls. RESULTS: We observed several frontostriatal regions that
      participated in reward processing in MDD. The common reward network in MDD was
      characterized by decreased subcortical and limbic areas activity and an increased
      cortical response. In addition, the cerebellum, lingual gyrus, parahippocampal
      gyrus and fusiform gyrus preferentially responded to positive stimuli in MDD,
      while the insula, precuneus, cuneus, PFC and inferior parietal lobule selectively
      responded to monetary rewards. Our results indicated a reduced caudate response
      during both monetary anticipation and outcome stages as well as increased
      activation in the middle frontal gyrus and dorsal anterior cingulate during
      reward anticipation in MDD. LIMITATIONS: The reward-related tasks and mood states
      of patients included in our analysis were heterogeneous. CONCLUSIONS: Our current
      findings suggest that there exist emotional or motivational pathway dysfunctions
      in MDD during reward-related processing. Future studies may be strengthened by
      paying careful attention to the types of reward used as well as the different
      components of reward processing examined.

PMID- 23856281
TI  - Subthreshold depression in children and adolescents - a systematic review.
AB  - BACKGROUND: Depressive disorders are disabling conditions striking at all ages.
      In adults, subthreshold depression (SD) is viewed as being on a continuum with
      major depressive disorder (MDD). Whether this holds for children and adolescents,
      is still unclear. We performed the first systematic review of SD in subjects
      below 18 years, in order to explore if childhood SD and MDD share causal
      pathways, phenomenology and outcomes, supporting a dimensional view. METHODS: A
      critical systematic review in accordance with preferred reporting items for
      systematic reviews and meta-analyses (PRISMA) statement. A review protocol was
      developed a priori, and all reports were assessed by two reviewers. RESULTS: The
      literature search generated 941 eligible references and 24 studies were included.
      Although diagnostic criteria for SD showed great variability, similarities for SD
      and MDD were striking. Both were common conditions with similar risk factor
      patterns. Clinical characteristics in both groups were depressed mood, suicidal
      ideation and high comorbidity. Outcomes were almost equally poor, with increased
      psychiatric morbidity and health service use. SD intervention studies showed
      promising results. LIMITATIONS: Reports with data on SD not reported in keywords
      or abstract may have been missed by the search strategy. CONCLUSION: A
      dimensional view of depressive disorders is also supported in children and
      adolescents, suggesting SD to be a precursor to MDD. Although SD is a somewhat
      milder condition than MDD, it has severe outcomes with psychopathology and
      impairment. There is a need of identifying cost-efficient and longlasting
      interventions in order to prevent development of early SD into MDD.

PMID- 23856282
TI  - Affective temperaments are associated with specific clusters of symptoms and
      psychopathology: a cross-sectional study on bipolar disorder inpatients in acute
      manic, mixed, or depressive relapse.
AB  - BACKGROUND: The aim of this study was to assess whether different affective
      temperaments could be related to a specific mood disorder diagnosis and/or to
      different therapeutic choices in inpatients admitted for an acute relapse of
      their primary mood disorder. METHOD: Hundred and twenty-nine inpatients were
      consecutively assessed by means of the Structured and Clinical Interview for axis
      I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa,
      Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale
      for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global
      impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto
      Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of
      clinical and demographic data. RESULTS: The following prevalence rates for axis-I
      mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%),
      type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and
      schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale
      were significantly higher in BD-I and BD-NOS, and in mixed and manic acute
      states. Hyperthymic temperament was significantly more frequent in BD-I and BD
      NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and
      irritable temperaments were found more frequently in mixed episodes, while
      patients with depressive and mixed episodes more frequently exhibited anxious and
      depressive temperaments. Affective temperaments were associated with specific
      symptom and psychopathology clusters, with an orthogonal subdivision between
      hyperthymic temperament and anxious/cyclothymic/depressive/irritable
      temperaments. Therapeutic choices were often poorly differentiated among
      temperaments and mood states. LIMITS: Cross-sectional design; sample size.
      CONCLUSIONS: Although replication studies are needed, current results suggest
      that temperament-specific clusters of symptoms severity and psychopathology
      domains could be described.

PMID- 23856283
TI  - Use of the Suicide Status Form-II to investigate correlates of suicide risk
      factors in psychiatrically hospitalized children and adolescents.
AB  - BACKGROUND: Suicide is the third leading cause of death in the United States for
      youth 12-17 years or age. Acute psychiatric hospitalization represents a clear
      worst point clinically and acute suicide risk is the most common reason for
      psychiatric admission. We sought to determine factors associated with differences
      in individual suicide risk assessment for children and adolescents during acute
      psychiatric admission. METHODS: Study participants were 1153 youth consecutively
      admitted to an inpatient psychiatry unit who completed a self-administered
      Suicide Status Form (SSF) within 24h of admission. Additional information on
      suicide risk factors was obtained through medical chart abstraction. RESULTS:
      Females reported significantly greater psychological pain, stress, hopelessness,
      and self-hate on the SSF and were significantly more likely to have made a
      suicide attempt just prior to the index hospital admission (OR=1.59, SE=0.29;
      CI=1.12-2.26), report a family history of suicide (OR=2.02, SE=0.33; CI=1.47
      2.78), and had experienced a greater number of inpatient psychiatry admissions
      related to suicidal ideation (RR=1.33, SE=0.13; CI=1.10-1.61). High school aged
      youth and those with a primary diagnosis of depression displayed consistently
      elevated SSF scores and risk factors for suicide compared to comparison groups.
      LIMITATIONS: Diagnosis was determined through chart abstraction. Responses to
      access to firearm question had missing data for 46% of the total sample.
      CONCLUSIONS: Systematic administration of a suicide-specific measure at admission
      may help clinicians improve identification of suicide risk factors in youth in
      inpatient psychiatry settings.

PMID- 23856285
TI  - Exposure to light at night and risk of depression in the elderly.
AB  - BACKGROUND: Recent advances in understanding the fundamental links between
      chronobiology and depressive disorders have enabled exploring novel risk factors
      for depression in the field of biological rhythms. Increased exposure to light at
      night (LAN) is common in modern life, and LAN exposure is associated with
      circadian misalignment. However, whether LAN exposure in home settings is
      associated with depression remains unclear. METHODS: We measured the intensities
      of nighttime bedroom light and ambulatory daytime light along with overnight
      urinary melatonin excretion (UME) in 516 elderly individuals (mean age, 72.8).
      Depressive symptoms were assessed using the Geriatric Depression Scale. RESULTS:
      The median nighttime light intensity was 0.8lx (interquartile range, 0.2-3.3).
      The depressed group (n=101) revealed significantly higher prevalence of LAN
      exposure (average intensity, >= 5 lx) compared with that of the nondepressed
      group (n=415) using a multivariate logistic regression model adjusted for daytime
      light exposure, insomnia, hypertension, sleep duration, and physical activity
      [adjusted odds ratio (OR): 1.89; 95% confidence interval (CI), 1.10-3.25;
      P=0.02]. Consistently, another parameter of LAN exposure (duration of intensity
      >= 10 lx, >= 30 min) was significantly more prevalent in the depressed than in
      the nondepressed group (adjusted OR: 1.71; 95% CI, 1.01-2.89; P=0.046). In
      contrast, UME was not significantly associated with depressive symptoms.
      LIMITATION: Cross-sectional analysis. CONCLUSION: These results suggested that
      LAN exposure in home settings is significantly associated with depressive
      symptoms in the general elderly population. The risk of depression may be reduced
      by keeping nighttime bedroom dark.

PMID- 23856284
TI  - The role of family history in mental health service utilization for major
      depression.
AB  - BACKGROUND: The purpose of the study was to examine the association between
      family history of major depressive disorder (MDD) and mental health service
      utilization for MDD. METHODS: Data come from wave 1 (2001-2002) and wave 2 (2004
      2005) of the US National Epidemiologic Survey on Alcohol and Related Conditions
      (NESARC). The AUDADIS was used to determine the presence of lifetime and incident
      MDD. Participants with a mother, father, grandparent or sibling with MDD were
      considered to have a positive family history. Mental health service utilization
      among participants with lifetime MDD was studied. Data were analyzed using
      logistic regression models adjusted for socio-demographic characteristics (age,
      sex, education, marital status, family income) and disease severity. RESULTS:
      Approximately 7940 NESARC participants had lifetime MDD, 54.7% of them had family
      history of the disorder. Compared to participants with no family history of MDD,
      those with such family history were two times more likely to access treatment
      (OR: 2.37, 95% CI: 2.11-2.68). Parental, and particularly maternal history of
      MDD, was most strongly associated with MDD treatment. LIMITATIONS: Data were
      unavailable on the timing of family history of MDD and its possible under-report,
      and differences between participants with treated vs untreated relatives.
      Institutionalized individuals were not included. CONCLUSIONS: Individuals with
      parental and maternal history of major depression were two times more likely to
      receive treatment for MDD than those with no such history. Efforts to increase
      access to healthcare for those who do not report family history of MDD could
      prove effective in addressing existing unmet treatment needs.

PMID- 23856286
TI  - Minor hemoglobins HbA2 and HbF associate with disease severity in bipolar
      disorder with a likely protective role of HbA2 against post-partum episodes.
AB  - BACKGROUND: There exist studies indicating that bipolar disorder (BD) associates
      with changes in brain blood flow. Human brain with its high demand to oxygen
      constitutes 2% of the total body weight, while it receives 20% of cardiac output.
      alpha and beta globin chains of hemoglobin were recently found in neural tissues,
      yet no study has questioned blood hemoglobins in BD. METHODS: A total of 120
      euthymic BD patients (40 males and 80 females) were analyzed via high performance
      liquid chromatography (HPLC) to measure minor hemoglobin levels, which were
      statistically compared with disease characteristics. RESULTS: Minor hemoglobins
      HbA2 and HbF associated positively with episode density as a measure of disease
      severity in BD. An increased level of HbA2 meant significantly less postpartum
      episodes in child bearing women. HbF levels were higher in patients with a
      positive family history of any psychotic disorder. Sum of HbA2 and HbF correlated
      with episode density with a stronger significance (p<0.001) supporting
      intermittent hypoxia hypothesis in BD. LIMITATIONS: The study was conducted only
      on euthymic patients to avoid likely bigger exogenous effects such as electro
      convulsive therapy and diverse drug regimes, yet larger comparative studies are
      needed to support our current findings. CONCLUSIONS: Higher HbA2 and HbF in more
      severe bipolar disorder may be compensations against intermittent hypoxias in BD.
      HbA2 increases following myocardial angina and in mountain dwellers, which may
      indicate protective roles in extreme conditions. HbF increase may act more as a
      maladaptation or emerge via haplotypal associations of BD genes and gamma-globin
      locus at 11p15.5.

PMID- 23856287
TI  - The emerging roles of AhR in physiology and immunity.
AB  - The aryl hydrocarbon receptor (AhR) is traditionally defined as a transcriptional
      regulator involved in adaptive xenobiotic response, however, emerging evidence
      supports physiological functions of AhR in normal cell development and immune
      response. The role of AhR in immunomodulation is multi-dimensional. On the one
      hand, activation of AhR by TCDD and other ligands leads to profound
      immunosuppression, potentially via skewed Th1/Th2 cell balance toward Th1
      dominance, and boosted Treg cell differentiation. On the other hand, activation
      of AhR can also induce Th17 cell polarization and increase the severity of
      autoimmune disease. In addition to T lymphocytes, the AhR also appears to play a
      vital role in B cell maturation, and regulates the activity of macrophages,
      dendritic cells and neutrophils following lipopolysaccharide challenge or
      influenza virus infection. In these scenarios, activation of AhR is associated
      with decreased host response and reduced survival. Furthermore, gene knock out
      studies suggest that AhR is indispensable for the postnatal maintenance of
      intestinal intraepithelial lymphocytes and skin-resident dendritic epidermal
      gamma delta T cells, providing a potential link between AhR and gut immunity and
      wound healing. It is well accepted that the magnitude and the type of immune
      response is dependent on the local cytokine milieu and the AhR appears to be one
      of the key factors involved in the fine turning of this cytokine balance. 

PMID- 23856288
TI  - Nicotinic acetylcholine receptors controlling attention: behavior, circuits and
      sensitivity to disruption by nicotine.
AB  - Attention is a central cognitive function that enables long-term engagement in a
      task and suppression of irrelevant information to obtain future goals. The
      prefrontal cortex (PFC) is the main link in integrating emotional and
      motivational state of an animal to regulate top-down attentional processes.
      Acetylcholine modulates PFC neuronal networks by activating nicotinic
      acetylcholine receptors (nAChRs) to support attention. However, how neuronal
      activity changes in the PFC during attention and which nAChR subtypes mediate
      this is only rudimentarily understood, but progress is being made. Recently,
      exciting new insights were obtained in the dynamics of cholinergic signaling in
      the PFC and modes of acetylcholine transmission via nAChRs in the cortex. In
      addition, mechanisms are uncovered on how the PFC circuitry is regulated by
      nAChRs. Novel studies show that endogenous activation of nAChRs in the PFC plays
      a central role in controlling attention. Here, we review current insights into
      how different subtypes of nAChRs expressed by distinct types of neurons in the
      PFC circuitry shape attention. In addition we discuss the impact of nicotine on
      the cholinergic system and prefrontal cortical circuits. Low concentrations of
      nicotine, as experienced by smokers, interfere with cholinergic signaling. In the
      long-term exposure to nicotine during adolescence leads to maladaptive
      adaptations of the PFC circuitry, which ultimately leads to a decrement in
      attention performance, again emphasizing the importance of nAChRs in attention. 

PMID- 23856291
TI  - Resolvin D1-mediated NOX2 inactivation rescues macrophages undertaking
      efferocytosis from oxidative stress-induced apoptosis.
AB  - Effective clearance of apoptotic cells by macrophages, termed efferocytosis, is
      pre-requisite for successful resolution of inflammation, and drives macrophage
      emigration to the draining lymph node, thereby promoting restoration of tissue
      homeostasis. During efferocytosis, engulfment of apopototic cells induces
      generation of reactive oxygen species in abundance. Macrophage apoptosis is an
      important feature of chronic inflammatory diseases including atherosclerosis. In
      the present study, we found that resolvin D1 (RvD1), one of endogenous pro
      resolving lipid mediators derived from docosahexaenoic acid, prevented apoptosis
      of murine macrophage-like RAW264.7 cells engulfing apoptotic T cells. The
      inhibitory effect of RvD1 on efferocytosis-induced oxidative burst appears to be
      mediated by the inactivation of NADPH oxidase (NOX), a key enzyme involved in
      intracellular ROS production. In RvD1-treated macrophages, efferocytosis-induced
      phosphorylation of p47(phox) and association between p47(phox) and gp91(phox)
      were downregulated, resulting in abrogation of generation of superoxide anion and
      hydrogen peroxide. Furthermore, RvD1-mediated suppression of NOX activation was
      found to be dependent on cAMP-activated protein kinase (PKA) signaling. Besides
      inhibiting NOX activation, RvD1 rescued macrophages from oxidative stress-induced
      apoptosis by upregulating the expression of Bcl-xL and Bcl-2. However, knockdown
      of the RvD1 receptor, lipoxin A receptor/formyl-peptide receptor (ALX/FPR2),
      abolished the ability of RvD1 to activate cAMP-PKA signaling, to suppress NOX
      activation and to increase the expression of anti-apoptotic proteins, suggesting
      that ALX/FPR2 mediates the protective effect of RvD1 on effeocytosis-induced
      oxidative stress. Taken together, these findings indicate that RvD1 rescues
      macrophages from oxidative stress-induced apoptosis during efferocytosis through
      PKA-mediated repression of NOX activation and upregulation of anti-apoptotic
      protein expression. 

PMID- 23856290
TI  - EMMPRIN-mediated induction of uterine and vascular matrix metalloproteinases
      during pregnancy and in response to estrogen and progesterone.
AB  - Pregnancy is associated with uteroplacental and vascular remodeling in order to
      adapt for the growing fetus and the hemodynamic changes in the maternal
      circulation. We have previously shown upregulation of uterine matrix
      metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes
      in MMPs are localized to the uterus or are generalized in feto-placental and
      maternal circulation is unclear. Also, the mechanisms causing the changes in
      uteroplacental and vascular MMPs during pregnancy are unclear. MMPs expression,
      activity and tissue distribution were measured in uterus, placenta and aorta of
      virgin, mid-pregnant (mid-Preg) and late pregnant (late-Preg) rats. Western blots
      and gelatin zymography revealed increases in MMP-2 and -9 in uterus and aorta of
      late-Preg compared with virgin and mid-Preg rats. In contrast, MMP-2 and -9 were
      decreased in placenta of late-Preg versus mid-Preg rats. Extracellular MMP
      inducer (EMMPRIN) was increased in uterus and aorta of pregnant rats, but was
      less in placenta of late-Preg than mid-Preg rats. Prolonged treatment of uterus
      or aorta of virgin rats with 17beta-estradiol and progesterone increased the
      amount of EMMPRIN, MMP-2 and -9, and the sex hormone-induced increases in MMPs
      were prevented by EMMPRIN neutralizing antibody. Immunohistochemistry revealed
      that MMP-2 and -9 and EMMPRIN increased in uterus and aorta of pregnant rats, but
      decreased in placenta of late-Preg versus mid-Preg rats. Thus pregnancy
      associated upregulation of uterine MMPs is paralleled by increased vascular MMPs,
      and both are mediated by EMMPRIN and induced by estrogen and progesterone,
      suggesting similar role of MMPs in uterine and vascular tissue remodeling and
      function during pregnancy. The decreased MMPs and EMMPRIN in placenta of late
      Preg rats suggests reduced role of MMPs in feto-placental circulation during late
      pregnancy. 

PMID- 23856292
TI  - Drug metabolizing enzyme and transporter protein profiles of hepatocytes derived
      from human embryonic and induced pluripotent stem cells.
AB  - Human embryonic and induced pluripotent stem cell-derived hepatocytes (hESC-Hep
      and hiPSC-Hep) have the potential to provide relevant human in vitro model
      systems for toxicity testing and drug discovery studies. In this study, the
      expression and function of important drug metabolizing cytochrome P450 (CYP)
      enzymes and transporter proteins in hESC-Hep and hiPSC-Hep were compared to
      cryopreserved human primary hepatocytes (hphep) and HepG2 cells. Overall, CYP
      activities in hESC-Hep and hiPSC-Hep were much lower than in hphep cultured for 4
      h, but CYP1A and 3A activities were comparable to levels in hphep cultured for
      48h (CYP1A: 35% and 26% of 48 h hphep, respectively; CYP3A: 80% and 440% of 48 h
      hphep, respectively). Importantly, in hESC-Hep and hiPSC-Hep, CYP activities were
      stable or increasing for at least one week in culture which was in contrast to
      the rapid loss of CYP activities in cultured hphep between 4 and 48 h after
      plating. With regard to transporters, in hESC-Hep and hiPSC-Hep, pronounced NTCP
      activity (17% and 29% of 4 h hphep, respectively) and moderate BSEP activity (6%
      and 8% of 4 h hphep, respectively) were observed. Analyses of mRNA expression and
      immunocytochemistry supported the observed CYP and transporter activities and
      showed expression of additional CYPs and transporters. In conclusion, the stable
      expression and function of CYPs and transporters in hESC-Hep and hiPSC-Hep for at
      least one week opens up the possibility to reproducibly perform long term and
      extensive studies, e.g. chronic toxicity testing, in a stem cell-derived hepatic
      system.

PMID- 23856289
TI  - Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the
      pathophysiology and treatment of schizophrenia.
AB  - The group of schizophrenia disorders affects approximately 1% of the population
      and has both genetic and environmental etiologies. Sufferers report various
      behavioral abnormalities including hallucinations and delusions (positive
      symptoms), reduced joy and amotivation (negative symptoms), plus inattention and
      poor learning (cognitive deficits). Despite the heterogeneous symptoms
      experienced, most patients smoke. The self-medication hypothesis posits that
      patients smoke to alleviate symptoms, consistent with evidence for nicotine
      induced enhancement of cognition. While nicotine acts on multiple nicotinic
      acetylcholine receptors (nAChRs), the primary target of research is often the
      homomeric alpha7 nAChR. Given genetic linkages between schizophrenia and this
      receptor, its association with P50 sensory gating deficits, and its reduced
      expression in post-mortem brains, many have attempted to develop alpha7 nAChR
      ligands for treating schizophrenia. Recent evidence that ligands can be
      orthosteric agonists or positive allosteric modulators (PAMs) has revitalized the
      hope for treatment discovery. Herein, we present evidence regarding: (1)
      pathophysiological alterations of alpha7 nAChRs that might occur in patients; (2)
      mechanistic evidence for the normal action of alpha7 nAChRs; (3) preclinical
      studies using alpha7 nAChR orthosteric agonists and type I/II PAMs; and (4) where
      successful translational testing has occurred for particular compounds, detailing
      what is still required. We report that the accumulating evidence is positive, but
      that greater work is required using positron emission tomography to understand
      current alterations in alpha7 nAChR expression and their relationship to
      symptoms. Finally, cross-species behavioral tasks should be used more regularly
      to determine the predictive efficacy of treatments. 

PMID- 23856293
TI  - Identification of Sirtuin 3, a mitochondrial protein deacetylase, as a new
      contributor to tamoxifen resistance in breast cancer cells.
AB  - The current study reports a previously unappreciated role of Sirtuin 3 (SIRT3), a
      mitochondrial protein deacetylase, in altering sensitivity of breast cancer cells
      to tamoxifen (Tam), a commonly used anti-estrogen agent. We showed that SIRT3 was
      significantly up-regulated at both mRNA and protein levels in the Tam-resistance
      human breast cancer cell line MTR-3, which was derived from MCF-7 line by
      continuous selective culture in the presence of 1MUM of Tam for two years. We
      further demonstrated that SIRT3 was rapidly up-regulated in the sensitive MCF-7
      cells following exposure to Tam. Transfection of MCF-7 cells with a SIRT3
      expression plasmid decreased cellular sensitivity to Tam and blocked the Tam
      induced apoptosis. Furthermore, silencing of SIRT3 expression in MTR-3 cells
      sensitized the resistant cells to Tam and enhanced apoptotic cell death. MTR-3
      cells with silencing of SIRT3 expression showed increases in the mitochondrial
      content of ERbeta, ROS level and apoptosis. These results not only uncovered a
      new role for SIRT3 in cancer but also identified this mitochondrial protein
      deacetylase as a previously unrecognized factor that participates in regulation
      of Tam sensitivity in breast cancer cells. Thus, SIRT3 might be considered as a
      potential target for overcoming Tam resistance in treatment of breast cancer. 

PMID- 23856294
TI  - Perceptions of short and long sleep duration and comorbid conditions: the PLATINO
      study.
AB  - OBJECTIVES: We aimed to describe the distribution of self-reported sleep duration
      in adults over the age of 40 years and to analyze the associated risk factors,
      comorbid conditions, and quality of life (QoL). METHODS: Our study was
      constructed as a cross-sectional population-based study and is part of the
      PLATINO (Spanish acronym for the Latin American Project for Research in Pulmonary
      Obstruction) study. It includes data from Mexico City (Mexico), Montevideo
      (Uruguay), Santiago (Chile), and Caracas (Venezuela). Data from 4533 individuals
      were analyzed using a single questionnaire entitled, PLATINO, which was designed
      to collect data on self-reported sleep symptoms. Spirometry also was performed in
      accordance with international standards. All statistical analyses took the study
      design into consideration with adjustments for each city. RESULTS: The prevalence
      of subjects who reported sleeping <7h was 38.4%, >= 7 to <9h was 51.4%, and >= 9h
      was 10.2%. In the multivariate analysis, individuals with shorter sleep duration
      had higher frequencies of insomnia, increased forced expiratory volume in one
      second in liters and percentage/forced vital capacity in liters (FEV1/FVC) of
      predicted ratios, and a higher presence of coughing and phlegm. The main risk
      factor associated with longer duration of sleep was the number of comorbidities.
      CONCLUSIONS: Self-reported sleep duration discriminated among groups that
      differed in sleep-related symptoms, respiratory symptoms, QoL and comorbid
      conditions.

PMID- 23856295
TI  - Longitudinal trends of the healthcare-seeking prevalence and incidence of
      insomnia in Taiwan: an 8-year nationally representative study.
AB  - OBJECTIVES: We used insurance claims of a nationally representative population
      based cohort to assess the longitudinal healthcare-seeking prevalence and
      incidence of insomnia. METHODS: Participants were identified from National Health
      Insurance enrollees in Taiwan during 2002 to 2009. Individuals with insomnia were
      identified using The International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) diagnostic and procedure codes of 780.52,
      307.41, and 307.42. RESULTS: In 2009 the prevalence of insomnia was 5.4% for
      women and 3.0% for men; the incidence of insomnia was 1.6% for women and 1.3% for
      men. Patients who were women (odds ratio [OR]), 1.82; 95% confidence interval
      [CI], 1.79-1.86), who were older (50-64 years: OR, 23.25; 95% CI, 21.07-25.64; >=
      65 years: OR, 24.70; 95% CI, 22.40-27.24), and who were in the middle
      socioeconomic status (SES) group (OR, 1.19; 95% CI, 1.16-1.21) were more likely
      to have insomnia. An inverse U-shaped woman-to-man ratio trend for the insomnia
      prevalence was found, and this ratio reached a peak around the menopausal
      transitional period. CONCLUSIONS: The persistence of healthcare-seeking behaviors
      with insomnia was more common in women. Our findings underscore the need to
      initiate treatment at an early stage as opposed to waiting for the spontaneous
      resolution of insomnia. Future research needs to identify causes of the
      persistence of insomnia and to develop proper interventions to reduce its rising
      prevalence. More active approaches toward preventive strategies for insomnia are
      needed, especially for women who are at higher risk for insomnia.

PMID- 23856296
TI  - AZD3480, a novel nicotinic receptor agonist, for the treatment of attention
      deficit/hyperactivity disorder in adults.
AB  - BACKGROUND: Laboratory studies have found that acute stimulation of nicotinic
      acetylcholine receptors improves cognition in adult attention
      deficit/hyperactivity disorder (ADHD). Clinical trials of nicotinic agonists have
      been mixed, underscoring the need to understand the mechanisms for individual
      differences in clinical response. Using cognitive models within a clinical trial
      framework may provide insight into these differences. METHODS: This was a within
      subjects, randomized, placebo-controlled double-blind trial of the nicotinic
      agonist AZD3480 (also termed TC-1734) at doses of 5 mg and 50 mg and placebo in
      adults with ADHD. The order of the 2-week treatment periods was randomized, and a
      3-week wash out separated each drug treatment period. Response inhibition (Stop
      Signal Task [SST]) and clinical efficacy (Investigator Rated Conners Adult ADHD
      Rating Scale [CAARS-INV]) were the a priori primary outcome measures of cognitive
      and clinical effects. We hypothesized that AZD3480 treatment would improve SST
      performance and clinical symptoms (CAARS-INV Total ADHD Symptoms Score). RESULTS:
      Thirty subjects were randomized, with 24 included in the intent-to-treat
      analyses. SST performance and total ADHD symptoms were significantly improved
      with 50 mg of AZD3480. CAARS-INV ratings of inattention, memory problems, and
      emotional lability/impulsivity were significantly improved with 50 mg of AZD3480.
      CONCLUSIONS: These results support previous work suggesting that nicotinic
      agonists are viable as treatments for adult ADHD. Measuring cognitive
      endophenotypes related to both the disorder and mechanism of treatment may help
      further rational drug development for dimensional features that cross-cut
      psychiatric disorders.

PMID- 23856297
TI  - Association among clinical response, hippocampal volume, and FKBP5 gene
      expression in individuals with posttraumatic stress disorder receiving cognitive
      behavioral therapy.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized by a reduced
      expression of FKBP5, a key modulator of the glucocorticoid receptor. Smaller
      hippocampal volume has also been documented in PTSD. We explored possible changes
      in FKBP5 gene expression and brain structure in patients with PTSD after
      cognitive behavioral therapy (CBT). METHODS: We measured peripheral FKBP5 RNA and
      volumes of the hippocampus, amygdala, and medial orbitofrontal cortex in 39
      patients with PTSD before and after CBT. The control subjects were 31 trauma
      exposed individuals without PTSD who were also assessed twice. Gene expression
      changes were screened with a microarray toolkit, which was followed by
      quantitative polymerase chain reaction for FKBP5 RNA. Brain volumes were measured
      using FreeSurfer. RESULTS: At baseline, patients with PTSD showed lower FKBP5
      gene expression and smaller hippocampal and medial orbitofrontal cortex, but not
      amygdala, volumes relative to control subjects. At follow-up, we found
      significantly increased FKBP5 expression and increased hippocampal volume in
      patients with PTSD. At follow-up, patients did not differ from control subjects
      in hippocampal volume. Improvement in PTSD symptoms was predicted by increased
      FKBP5 expression and increased hippocampal volume, but the primary predictor was
      FKBP5 expression. The most significantly altered gene expression in patients with
      PTSD relative to control subjects was found for ribosomal protein S6 kinase,
      which did not change after CBT and did not correlate with hippocampal volume.
      CONCLUSIONS: Clinical improvement in individuals with PTSD was associated with
      increased expression of FKBP5 and increased hippocampal volume, which were
      positively correlated.

PMID- 23856298
TI  - Monitoring of impact of anthropogenic inputs on water quality of mangrove
      ecosystem of Uran, Navi Mumbai, west coast of India.
AB  - Surface water samples were collected from substations along Sheva creek and
      Dharamtar creek mangrove ecosystems of Uran (Raigad), Navi Mumbai, west coast of
      India. Water samples were collected fortnightly from April 2009 to March 2011
      during spring low and high tides and were analyzed for pH, Temperature,
      Turbidity, Total solids (TS), Total dissolved solids (TDS), Total suspended
      solids (TSS), Dissolved oxygen (DO), Biochemical oxygen demand (BOD), Carbon
      dioxide (CO2), Chemical oxygen demand (COD), Salinity, Orthophosphate (O-PO4),
      Nitrite-nitrogen (NO2-N), Nitrate-nitrogen (NO3-N), and Silicates. Variables like
      pH, turbidity, TDS, salinity, DO, and BOD show seasonal variations. Higher
      content of O-PO4, NO3-N, and silicates is recorded due to discharge of domestic
      wastes and sewage, effluents from industries, oil tanking depots and also from
      maritime activities of Jawaharlal Nehru Port Trust (JNPT), hectic activities of
      Container Freight Stations (CFS), and other port wastes. This study reveals that
      water quality from mangrove ecosystems of Uran is deteriorating due to industrial
      pollution and that mangrove from Uran is facing the threat due to anthropogenic
      stress. 

PMID- 23856299
TI  - Brain volumetric abnormalities in patients with anorexia and bulimia nervosa: a
      voxel-based morphometry study.
AB  - Recent studies focussing on neuroimaging features of eating disorders have
      observed that anorexia nervosa (AN) is characterized by significant grey matter
      (GM) atrophy in many brain regions, especially in the cerebellum and anterior
      cingulate cortex. To date, no studies have found GM atrophy in bulimia nervosa
      (BN) or have directly compared patients with AN and BN. We used voxel-based
      morphometry (VBM) to characterize brain abnormalities in AN and BN patients,
      comparing them with each other and with a control group, and correlating brain
      volume with clinical features. We recruited 17 AN, 13 BN and 14 healthy controls.
      All subjects underwent high-resolution magnetic resonance imaging (MRI) with a T1
      weighted 3D image. VBM analysis was carried out with the FSL-VBM 4.1 tool. We
      found no global atrophy, but regional GM reduction in AN with respect to controls
      and BN in the cerebellum, fusiform area, supplementary motor area, and occipital
      cortex, and in the caudate in BN compared to AN and controls. Both groups of
      patients had a volumetric increase bilaterally in somatosensory regions with
      respect to controls, in areas that are typically involved in the sensory-motor
      integration of body stimuli and in mental representation of the body image. Our
      VBM study documented, for the first time in BN patients, the presence of
      volumetric alterations and replicated previous findings in AN patients. We
      evidenced morphological differences between AN and BN, demonstrating in the
      latter atrophy of the caudate nucleus, a region involved in reward mechanisms and
      processes of self-regulation, perhaps involved in the genesis of the binge-eating
      behaviors of this disorder. 

PMID- 23856300
TI  - The Hitchhiker's guide to the blood system.

PMID- 23856301
TI  - Simultaneous and complete genome sequencing of influenza A and B with high
      coverage by Illumina MiSeq Platform.
AB  - Active global surveillance and characterization of influenza viruses are
      essential for better preparation against possible pandemic events. Obtaining
      comprehensive information about the influenza genome can improve our
      understanding of the evolution of influenza viruses and emergence of new strains,
      and improve the accuracy when designing preventive vaccines. This study
      investigated the use of deep sequencing by the next-generation sequencing (NGS)
      Illumina MiSeq Platform to obtain complete genome sequence information from
      influenza virus isolates. The influenza virus isolates were cultured from 6
      respiratory acute clinical specimens collected in Thailand and Nepal. DNA
      libraries obtained from each viral isolate were mixed and all were sequenced
      simultaneously. Total information of 2.6 Gbases was obtained from a 455+/-14
      K/mm2 density with 95.76% (8,571,655/8,950,724 clusters) of the clusters passing
      quality control (QC) filters. Approximately 93.7% of all sequences from Read1 and
      83.5% from Read2 contained high quality sequences that were >=Q30, a base calling
      QC score standard. Alignments analysis identified three seasonal influenza A H3N2
      strains, one 2009 pandemic influenza A H1N1 strain and two influenza B strains.
      The nearly entire genomes of all six virus isolates yielded equal or greater than
      600-fold sequence coverage depth. MiSeq Platform identified seasonal influenza A
      H3N2, 2009 pandemic influenza A H1N1and influenza B in the DNA library mixtures
      efficiently.

PMID- 23856302
TI  - Does the burden of the experience sampling method undermine data quality in state
      body image research?
AB  - Despite growing popularity of experience sampling methodology (ESM) for
      evaluations of state-based components of body image, there have been concerns
      that the frequent repeated measurement might encourage problematic responding
      resulting in low data quantity and/or quality. Using a sample of 105 women (mean
      age=24.84), this study used multilevel modelling to investigate whether (a) there
      were changes in compliance or response variability across a 7-day period, and (b)
      whether such changes are explained by participant characteristics. Present
      findings suggest that demands of ESM protocol undermine quantity more so than
      quality of obtained data. Decline in procedural compliance across the testing
      period correlated with BMI and body shame, whereas reduced variability in state
      based assessments did not adversely impact the strength of association between
      state body satisfaction ratings and other variables in the dataset. The authors
      make several recommendations for ensuring the quality of ESM-based data in future
      studies. 

PMID- 23856303
TI  - A systematic review of studies comparing body image concerns among female college
      athletes and non-athletes, 1997-2012.
AB  - Research prior to 2001 indicated that athletes experienced better body image than
      non-athletes, with no differences among sport types. Since then, female athletes
      have become increasingly sexually objectified in the media, and the sociocultural
      beauty ideal has shifted to emphasize appearing both athletic and thin. Part I of
      this paper explores the literature describing these changes. Part II presents a
      systematic and comprehensive literature review of 10 recent studies comparing
      body image concerns (BIC) among collegiate female athletes and non-athletes to
      identify the current status of BIC in female athletes. Findings indicate that
      involvement in collegiate athletics provides some protection from BIC; however,
      this protection appears attenuated for athletes in more feminine sports (e.g.,
      gymnastics), and higher level athletes (Division I). Researchers should examine
      how sociocultural pressures unrelated to competition predict female athletes' BIC
      using measures that focus on objectification, positive body image, body
      functionality, and thin- and athletic-ideal internalization. 

PMID- 23856304
TI  - Metals in bioenergetics and biomimetics systems.

PMID- 23856305
TI  - Innovative method using circulating tumor cells for prediction of the effects of
      induction therapy on locally advanced non-small cell lung cancer.
AB  - BACKGROUND: The existence of circulating tumor cells (CTCs) in patients with lung
      cancer has been reported. The purpose of this study was to assess whether CTCs
      are predictive of the pathological effects of induction chemoradiotherapy for
      patients with non-small cell lung cancer. METHODS: Patients who underwent
      induction chemoradiotherapy followed by surgery were compared with those who
      underwent surgery alone. Peripheral and pulmonary venous blood samples from the
      involved lobe were collected intraoperatively, and the number of CTCs was counted
      using the CellSearchTM system, an epithelial cell adhesion molecule-based
      immunomagnetic technique. RESULTS: Of the 9 patients who underwent induction
      therapy, 4 achieved pathological CR, 4 achieved major response, and 1 achieved
      minor response. All patients who underwent induction therapy and surgery alone
      were negative for CTCs in peripheral blood. In the induction therapy group, 4
      patients showing pathological CR were negative for CTCs in pulmonary venous blood
      (pvCTCs) and 5 showing major/minor response were positive (mean, 57.8 cells). The
      numbers of CTCs in patients showing major/minor response were significantly
      higher than those in patients showing pathological CR (p = 0.012, Mann-Whitney U
      test). All 6 patients undergoing surgery alone were positive for pvCTCs (mean,
      207.5 cells), showing a significant difference from those undergoing induction
      therapy (p = 0.038). CONCLUSIONS: The existence of CTCs in pulmonary venous blood
      reflects pathological non-CR, and therapeutic pathological response may be
      predicted by pvCTC measurement.

PMID- 23856306
TI  - Use of polymer-bound Schiff base as a new liquid binding agent of diffusive
      gradients in thin-films for the measurement of labile Cu2+, Cd2+ and Pb2+.
AB  - A new diffusive gradients in thin-films (DGT) device with solution of polymer
      bound Schiff base (Py-PEI) derived from poly(ethyleneimine) and 2
      pyridinecarboxaldehyde as the binding agent (Py-PEI DGT) was developed for
      measuring labile Cu(2+), Cd(2+) and Pb(2+) in waters. In synthetic solution,
      uptake percentages of Cu(2+), Cd(2+) and Pb(2+) by Py-PEI DGT were 99.2 +/- 4.4%,
      103.7 +/- 4.8% and 98.7 +/- 5.5% of the total metals, respectively. Performance
      of Py-PEI DGT was independent of pH 4-8.5 and ionic strength 1 * 10(-4)-0.1 mol
      L(-1). The uptake of labile metals showed agreement with the theoretical values
      of free ions in EDTA solution, and decreased with increase of humic acid (HA) and
      dissolved organic carbon (DOC) contents in water due to the complexation of HA
      and DOC with metals. DGT devices containing different liquid binding agents (Py
      PEI, polyacrylate (PA) and poly(4-styrenesulfonate) (PSS)) were deployed in the
      same solution. The higher uptake percentages of Py-PEI DGT (13.2 +/- 1.1, 26.5 +/
      2.4 and 62.7 +/- 3.2% of total Cu(2+), Cd(2+) and Pb(2+)) were obtained with
      respective to PSS DGT (6.7 +/- 0.6, 9.2 +/- 0.9 and 29.6 +/- 2.7% of total above
      metals) and PA DGT (8.9 +/- 0.9 and 16.2 +/- 1.1% of total Cu(2+) and Cd(2+)) due
      to its relatively strong binding affinity with metals.

PMID- 23856307
TI  - In vivo biodistribution and synergistic toxicity of silica nanoparticles and
      cadmium chloride in mice.
AB  - Silica nanoparticles (SiNPs) are now in daily use due to their low intrinsic
      toxicity. Cadmium is a ubiquitous environmental pollutant. In spite of real risk
      of humans' co-exposure to SiNPs and cadmium, their synergistic toxicity is still
      unclear. Here, we report the synergistic effects of SiNPs and CdCl2 on their
      biodistribution and subacute toxicity in mice. The biodistributions,
      histopathological changes, serum biochemical parameters and oxidative stress
      responses were determined after intraperitoneal injection of SiNPs and/or CdCl2
      to mice. SiNPs and CdCl2 have a positive synergistic toxicity in mice. Although
      SiNPs were low toxic to mice, co-exposure of SiNPs and CdCl2 significantly
      enhanced CdCl2-induced oxidative damage in the liver as indicated by the severe
      liver dysfunction and histopathological abnormalities. Co-exposure to SiNPs and
      CdCl2 markedly increased the cadmium accumulation in the liver, which induced
      significant hepatic oxidative stress. In vitro binding assays indicated that
      serum albumin and Cd(2+) mutually enhanced the binding of each other to SiNPs via
      the interaction of serum albumin and Cd(2+). The uptake of serum albumin- and
      Cd(2+)-bound SiNPs by the macrophages significantly increased cadmium
      accumulation in mice. These results demonstrate that serum albumins play an
      important role in the positive synergistic toxicity of SiNPs and CdCl2.

PMID- 23856308
TI  - Adsorption of Cr(VI) using synthetic poly(m-phenylenediamine).
AB  - Poly(m-phenylenediamine) (PmPD) with different oxidation state was successfully
      synthesized by the improved chemically oxidative polymerization. The function of
      oxidation state on Cr(VI) adsorption was systematically examined through
      adsorption experiments. Results showed that the Cr(VI) adsorptivity of all PmPD
      increased with decreasing the initial pH. When the oxidation state of PmPD was
      dropped, the equilibrium time for Cr(VI) adsorption was obviously shortened and
      its Cr(VI) removal and adsorption selectivity were profoundly obviously
      increased. Typically, PmPD with the lowest oxidation state in this research
      possesses the highest Cr(VI) removal of 500 mg g(-1). Moreover, PmPD with lower
      oxidation state displays a potentially superior prospect in Cr(VI) treatment
      through preliminary experiments on 5 cycles of adsorption, column adsorption and
      practical wastewater treatment. The possible adsorption mechanism was discussed
      mainly according to characterizations (FTIR, XPS) and experiments, which together
      suggests that the Cr(VI) adsorption most possibly involve redox reaction,
      chelation and doping adsorption.

PMID- 23856309
TI  - An environmentally friendly method for the fabrication of reduced graphene oxide
      foam with a super oil absorption capacity.
AB  - Three kinds of graphene oxide (GO) foams were fabricated using different freezing
      methods (unidirectional freezing drying (UDF), non-directional freezing drying,
      and air freezing drying), and the corresponding reduced graphene oxide (RGO)
      foams were prepared by their thermal reduction of those GO foams. These RGO foams
      were characterized by Fourier transform infrared spectroscopy, thermal
      gravimetric analysis, X-ray diffraction, X-ray photoelectron spectroscopy, and
      scanning electron microscopy. The absorption process and the factors that
      influence the absorption capacity were investigated. The RGO foams are
      hydrophobic and showed extremely high absorbing abilities for organic liquids.
      The absorption capacity of the RGO foams made by UDF was higher than 100 g g(-1)
      for all the oils tested (gasoline, diesel oil, pump oil, lubricating oil and
      olive oil) and had the highest value of about 122 g g(-1) for olive oil. The oil
      absorption capacity of the GO foams was lower than that of the RGO foams, but for
      olive oil, the absorption capacity was still high than 70 g g(-1), which is
      higher than that of most oil absorbents.

PMID- 23856310
TI  - Formation and speciation of nine haloacetamides, an emerging class of nitrogenous
      DBPs, during chlorination or chloramination.
AB  - Haloacetamides (HAcAms) are an emerging class of nitrogenous disinfection by
      products (N-DBPs) of health concern. However, there are very limited data on the
      formation and speciation of the nine bromine- and chlorine-containing
      haloacetamides (HAcAm9). In the study, their formation and speciation during
      chlor(am)ination were investigated for a group of waters with a range of specific
      ultraviolet absorbance at 254 nm (SUVA254), dissolved organic nitrogen (DON), and
      bromide levels. The waters that were the least impacted by anthropogenic
      pollution had the lowest DON levels, the highest ratios of dissolved organic
      carbon (DOC) to DON, and exhibited the least HAcAm9 formation. DON/DOC may act as
      an indicator of HAcAm yields during chlorination. HAcAm9 exhibited more formation
      during chloramination in the low-SUVA waters with no bromide, relative to high
      SUVA waters with bromide. The selected waters all formed primarily dihalogenated
      (di-) HAcAms, followed by trihalogenated (tri-) species and, to a much lesser
      extent, monohalogenated (mono-) HAcAms. Di-HAcAm formation had similar trends as
      that of HAcAm9; whereas chloramination formed more mono- and less tri-HAcAms than
      chlorination. Bromine utilization factors and bromine incorporation factor
      increased with decreasing and increasing bromide during either chlorination or
      chloramination, and bromine was easier to incorporate into tri-HAcAms during
      chloramination than chlorination.

PMID- 23856311
TI  - Recycling the product of thermal transformation of cement-asbestos for the
      preparation of calcium sulfoaluminate clinker.
AB  - According to recent resolutions of the European Parliament (2012/2065(INI)), the
      need for environmentally friendly alternative solutions to landfill disposal of
      hazardous wastes, such as asbestos-containing materials, prompts their recycling
      as secondary raw materials (end of waste concept). In this respect, for the first
      time, we report the recycling of the high temperature product of cement-asbestos,
      in the formulation of calcium sulfoaluminate cement clinkers (novel cementitious
      binders designed to reduce CO2 emissions), as a continuation of a previous work
      on their systematic characterization. Up to 29 wt% of the secondary raw material
      was successfully introduced into the raw mix. Different clinker samples were
      obtained at 1250  degrees C and 1300  degrees C, reproducing the phase
      composition of industrial analogues. As an alternative source of Ca and Si, this
      secondary raw material allows for a reduction of the CO2 emissions in cement
      production, mitigating the ecological impact of cement manufacturing, and
      reducing the need for natural resources.

PMID- 23856312
TI  - Viability study of automobile shredder residue as fuel.
AB  - Car Fluff samples collected from a shredding plant in Italy were classified based
      on particle size, and three different size fractions were obtained in this way. A
      comparison between these size fractions and the original light fluff was made
      from two different points of view: (i) the properties of each size fraction as a
      fuel were evaluated and (ii) the pollutants evolved when each size fraction was
      subjected to combustion were studied. The aim was to establish which size
      fraction would be the most suitable for the purposes of energy recovery. The
      light fluff analyzed contained up to 50 wt.% fines (particle size<20 mm).
      However, its low calorific value and high emissions of polychlorinated dioxins
      and furans (PCDD/Fs), generated during combustion, make the fines fraction
      inappropriate for energy recovery, and therefore, landfilling would be the best
      option. The 50-100 mm fraction exhibited a high calorific value and low PCDD/F
      emissions were generated when the sample was combusted, making it the most
      suitable fraction for use as refuse-derived fuel (RDF). Results obtained suggest
      that removing fines from the original ASR sample would lead to a material product
      that is more suitable for use as RDF.

PMID- 23856313
TI  - Biodegradation characteristics and size fractionation of landfill leachate for
      integrated membrane treatment.
AB  - The fate of organics and nitrogen during the biological treatment with MBR and
      subsequent membrane filtration processes (nano filtration, NF; reverse osmosis,
      RO) were investigated for a landfill leachate. The chemical oxygen demand (COD)
      and total Kjeldahl nitrogen (TKN) removal performances of membrane bioreactor
      (MBR) were obtained to be around 89% and 85%, respectively. The effluent COD of
      MBR was measured to be 1935 mg/L (30 kDa) which is much lower than experimentally
      determined soluble inert COD of 3200 mg/L using 0.45 MUm filter. The readily and
      slowly biodegradable COD fractions were estimated to be 17% and 52% of raw
      influent COD, respectively. The respirometry based modeling test performed on raw
      leachate exhibited much slower degradation kinetics compared to municipal
      wastewater. A unique subset of model parameters was extracted from batch
      respirometry by using acclimated MBR sludge. The sequential ultrafiltration (UF)
      experiments (particle size distribution, PSD) revealed that most of the organics
      was below 2 nm filter mesh size. In addition, NF/RO post treatment after MBR
      system was required to increase COD and total nitrogen (TN) removal performances
      up to 99%. Relatively lower salt rejection rates around 94% was obtained for RO
      system as a post treatment of MBR system.

PMID- 23856314
TI  - Architecture of optical sensor for recognition of multiple toxic metal ions from
      water.
AB  - Here, we designed novel optical sensor based on the wormhole hexagonal mesoporous
      core/multi-shell silica nanoparticles that enabled the selective recognition and
      removal of these extremely toxic metals from drinking water. The surface-coating
      process of a mesoporous core/double-shell silica platforms by several consequence
      decorations using a cationic surfactant with double alkyl tails (CS-DAT) and then
      a synthesized dicarboxylate 1,5-diphenyl-3-thiocarbazone (III) signaling probe
      enabled us to create a unique hierarchical multi-shell sensor. In this design,
      the high loading capacity and wrapping of the CS-DAT and III organic moieties
      could be achieved, leading to the formation of silica core with multi-shells that
      formed from double-silica, CS-DAT, and III dressing layers. In this sensing
      system, notable changes in color and reflectance intensity of the multi-shelled
      sensor for Cu(2+), Co(2+), Cd(2+), and Hg(2+) ions, were observed at pH 2, 8, 9.5
      and 11.5, respectively. The multi-shelled sensor is added to enable accessibility
      for continuous monitoring of several different toxic metal ions and efficient
      multi-ion sensing and removal capabilities with respect to reversibility,
      selectivity, and signal stability. 

PMID- 23856315
TI  - Adsorption and sequential degradation of polybrominated diphenyl ethers with
      zerovalent iron.
AB  - The widely used flame retardants, polybrominated diphenyl ethers (PBDEs), have
      been regulated owing to their persistence and toxicity. However, the high and
      increasing accumulation amount of PBDEs in the environment raises a big concern
      for public safety. In this study, the removal processes of decabromodiphenyl
      ether (BDE-209) and monobromodiphenyl ether (BDE-3) with microscale zerovalent
      iron (MZVI) were investigated to get better understandings for the removal
      mechanism based upon adsorption and degradation. The removal kinetics of both
      compounds was analyzed and revealed two-step kinetics: a fast removal step at the
      beginning of the reaction and a follow-up slow removal step. By-products
      generated during the entire process followed a stepwise sequence. The content of
      brominated compounds on the surface of MZVI was measured. About 10-20% of BDE-209
      and 15-30% of BDE-3 were adsorbed on MZVI. The adsorption of BDE-209 and BDE-3 on
      MZVI was confirmed through the Fourier transform infrared spectroscopy. Surface
      adsorption of PBDEs on MZVI dominates the removal mechanism in the beginning and
      further debromination with MZVI was found. Finally, about 70% of BDE-209 and 60%
      of BDE-3 was degraded by MZVI within about one month. Our findings provide
      evidences for understanding the removal mechanism of PBDEs with MZVI and its
      great longevity on the PBDE degradation, which can facilitate the remediation
      design. 

PMID- 23856316
TI  - Dutch midwives' behavioural intentions of antenatal management of maternal
      distress and factors influencing these intentions: an exploratory survey.
AB  - OBJECTIVE: to explore midwives' behavioural intentions and the determinants of
      these intentions with regard to the management of antenatal care of women with
      maternal distress. DESIGN: an exploratory survey using a questionnaire.
      Descriptive statistics calculated expanded TPB constructs, demographic
      information, personal characteristics and work related details. Multiple linear
      regression analyses were used to examine which factors influence midwives'
      intention to provide antenatal care of maternal distress. SETTING: midwives
      working in Dutch primary care. PARTICIPANTS: 112 midwives completed the survey.
      RESULTS: midwives did not report a clear intention to screen for maternal
      distress (3.46 +/- 1.8). On average, midwives expressed a positive intention to
      support women with maternal distress (4.63 +/- 1.57) and to collaborate with
      other health-care professionals (4.63 +/- 1.57). Finding maternal distress an
      interesting topic was a positive predictor for the intention to screen (B=0.383;
      p=0.005), to support (B=0.637; p=<0.000) and to collaborate (B=0.455; p=0.002).
      Other positive predictors for the intention to screen for maternal distress were
      years of work experience (B=0.035; p=0.028), attitude about the value of
      screening (B=0.326; p=0.002), and self-efficacy (B=0.248; p=0.004). A positive
      attitude toward support for women with maternal distress (B=0.523; p=0.017)
      predicted the intention to support these women. Number of years of work
      experience (B=0.042; p=0.017) was a positive predictor for the intention to
      collaborate with other health-care professionals. KEY CONCLUSIONS: the intention
      to screen for maternal distress was less evident than the intention to support
      women with maternal distress and the intention to collaborate with other health
      care professionals. Important factors predicting the midwife's intention to
      screen, support and collaborate were finding maternal distress an interesting
      topic, years of work experience, attitude about the value of screening and
      support and self-efficacy about screening. IMPLICATIONS FOR PRACTICE: to provide
      care involving all three components of antenatal management of maternal distress
      implies efforts to influence the factors that predict the intention to screen, to
      support women with maternal distress and the intention to collaborate with other
      health-care professionals.

PMID- 23856317
TI  - Evaluation of blood pressure measurements in first ambulatory neurological
      consultations: a missed part of the physical examination?
AB  - OBJECTIVE: To obtain a blood pressure reading is mandatory during either the
      general or specialized physical examination. This study describes factors
      associated with the accomplishment of blood pressure measurement in the first
      neurological consultation. METHODS: We studied first ambulatory neurology
      consultations in a Mexican referral hospital. Demographic characteristics,
      diagnostic category of referral, final diagnosis and data on physical examination
      were collected to establish a logistic regression analysis in order to identify
      factors associated with the accomplishment of blood pressure measurement.
      RESULTS: Over 8 months 778 outpatients were studied. The most frequent diagnoses
      for first consultation were headache (26%), epilepsy (14%) and stroke (13%). Only
      in 39% (n=301) of the outpatients blood pressure was registered, among them, 30%
      had normal blood pressure, 43% had 121-139/81-89 mmHg, 20% had 140-159/90-99 mmHg
      and 7% had >= 160/100 mmHg. The independent factors that favored the practice of
      BP determination in multivariable analysis were >65 years of age (odds ratio:
      2.26; 95% confidence interval: 1.52-3.36) and headache complaint (odds ratio:
      1.81, 95% confidence interval: 1.30-2.53). Notably, only 43% of patients with
      stroke had blood pressure registration, even when these stroke patients had blood
      pressure readings, they had higher blood pressure than with other diagnoses
      (p<0.05). CONCLUSION: Blood pressure registration was frequently omitted from the
      first neurological consultation, particularly in outpatients who might need it
      the most.

PMID- 23856318
TI  - Cardiopulmonary exercise testing in healthy children and adolescents at
      moderately high altitude.
AB  - OBJECTIVE: Cardiopulmonary exercise testing is a tool that helps clinicians to
      establish diagnosis and calculate risk stratification in adults. However, the
      utility of this test among children with congenital heart disease has not been
      fully explored. The goal of this study was to describe reference values for
      cardiopulmonary performance of healthy children. METHODS: This study included 103
      apparently healthy children (aged from 4 to 18 years; 61 boys), who underwent
      cardiopulmonary test using a treadmill protocol. All tests took place at 2240m
      above sea level (Mexico City). RESULTS: Exercise time was 11+/-4min. There were
      no complications. Peak oxygen uptake correlated closely with height in both
      genders (girls r=0.84; boys r=0.84, p<0.001). A multivariable linear regression
      model showed that body surface area, exercise time, gender and heart rate reserve
      were significant predictors of peak oxygen uptake (R(2)=0.815, p<0.001). Peak
      oxygen uptake was strongly associated with age even among children younger than
      thirteen years (r=0.74, p<0.001). CONCLUSION: This study provides physiological
      values for the major cardiopulmonary variables obtained from exercise testing
      using a treadmill among healthy children. Cardiopulmonary exercise test can be
      safely and effectively performed in young children even as young as 4 years old.
      Variables including age, gender and height are strongly associated with exercise
      time, peak heart rate and peak oxygen uptake. Regression equations for predicting
      peak heart rate and peak oxygen uptake are presented as reference values that
      allow researchers to compare children with heart disease versus those who are
      healthy.

PMID- 23856319
TI  - The 5-HTTLPR genotype and depressiveness link: contribution of aspects of
      environment and gender.

PMID- 23856320
TI  - Advances in genetic modification of pluripotent stem cells.
AB  - Genetically engineered stem cells aid in dissecting basic cell function and are
      valuable tools for drug discovery, in vivo cell tracking, and gene therapy. Gene
      transfer into pluripotent stem cells has been a challenge due to their intrinsic
      feature of growing in clusters and hence not amenable to common gene delivery
      methods. Several advances have been made in the rapid assembly of DNA elements,
      optimization of culture conditions, and DNA delivery methods. This has lead to
      the development of viral and non-viral methods for transient or stable
      modification of cells, albeit with varying efficiencies. Most methods require
      selection and clonal expansion that demand prolonged culture and are not suited
      for cells with limited proliferative potential. Choosing the right platform based
      on preferred length, strength, and context of transgene expression is a critical
      step. Random integration of the transgene into the genome can be complicated due
      to silencing or altered regulation of expression due to genomic effects. An
      alternative to this are site-specific methods that target transgenes followed by
      screening to identify the genomic loci that support long-term expression with
      stem cell proliferation and differentiation. A highly precise and accurate
      editing of the genome driven by homology can be achieved using traditional
      methods as well as the newer technologies such as zinc finger nuclease, TAL
      effector nucleases and CRISPR. In this review, we summarize the different genetic
      engineering methods that have been successfully used to create modified embryonic
      and induced pluripotent stem cells. 

PMID- 23856322
TI  - In vivo assessment of the three-dimensional haemodynamic micro-environment
      following drug-eluting bioresorbable vascular scaffold implantation in a human
      coronary artery: fusion of frequency domain optical coherence tomography and
      angiography.

PMID- 23856321
TI  - Luminescent multiplex viability assay for Trypanosoma brucei gambiense.
AB  - BACKGROUND: New compounds for the treatment of human African trypanosomiasis
      (HAT) are urgently required. Trypanosoma brucei (T.b.) gambiense is the leading
      cause of HAT, yet T.b. gambiense is often not the prime target organism in drug
      discovery. This may be attributed to the difficulties in handling this subspecies
      and the lack of an efficient viability assay to monitor drug efficacy. METHODS:
      In this study, a T.b. gambiense strain, recently isolated in the D.R. Congo, was
      made bioluminescent by transfection with Renilla luciferase (RLuc) without
      altering its in vitro and in vivo growth characteristics. A luminescent multiplex
      viability assay (LMVA), based on measurement of the Renilla luciferase activity
      and the ATP content of the cells within the same experiment, was investigated as
      an alternative to the standard fluorimetric resazurin viability assay for drug
      sensitivity testing of T.b. gambiense. RESULTS: In a 96-well format, the RLuc
      transfected strain showed a detection limit of 2 * 10(4) cells ml(-1) for the
      Renilla luciferase measurement and 5 * 10(3) cells ml(-1) for the ATP
      measurement. Both assays of the LMVA showed linearity up to 10(6) cells ml(-1)
      and correlated well with the cell density during exponential growth of the long
      slender bloodstream forms. The LMVA was compared to the fluorimetric resazurin
      viability assay for drug sensitivity testing of pentamidine, eflornithine,
      nifurtimox and melarsoprol with both the wild type and the RLuc transfected
      population. For each drug, the IC50 value of the RLuc population was similar to
      that of the wild type when determined with either the fluorimetric resazurin
      method or the LMVA. For eflornithine, nifurtimox and melarsoprol we found no
      difference between the IC50 values in both viability assays. In contrast, the
      IC50 value of pentamidine was higher when determined with the fluorimetric
      resazurin method than in both assays of the LMVA. CONCLUSIONS: LMVA has some
      advantages for viability measurement of T.b. gambiense: it requires less
      incubation time for viability detection than the fluorimetric resazurin assay and
      in LMVA, two sensitive and independent viability assays are performed in the same
      experiment.

PMID- 23856323
TI  - Chronic mild sleep restriction accentuates contextual memory impairments, and
      accumulations of cortical Abeta and pTau in a mouse model of Alzheimer's disease.
AB  - Age-associated dysregulation of sleep can be worsened by Alzheimer's disease
      (AD). AD and sleep restriction both impair cognition, yet it is unknown if mild
      chronic sleep restriction modifies the proteopathic processes involved in AD. The
      goal of this work was to test the hypothesis that sleep restriction worsens
      memory impairments, and amyloid beta-peptide (Abeta) and pTau accumulations in
      the brain in a mouse model of AD, with a focus on a role for circulating
      glucocorticoids (GC). Male 3xTgAD mice were subjected to sleep restriction (SR)
      for 6h/day for 6 weeks using the modified multiple platform technique, and
      behavioral (Morris water maze, fear conditioning, open field) and biochemical
      (immunoblot) outcomes were compared to mice undergoing daily cage transfers
      (large cage control; LCC) as well as control mice that remained in their home
      cage (control; CTL). At one week, both LCC and SR mice displayed significant
      elevations in plasma corticosterone compared to CTL (p<0.002). By four weeks, SR
      mice displayed a two-fold increase in circulating corticosterone levels compared
      to CTL. Behavioral data indicated deficits in contextual and cued memory in SR
      mice that were not present for LCC or CTL (p<0.04). Both Abeta and pTau levels
      increased in the cortex of SR mice compared to CTL and LCC; however these changes
      were not noted in the hippocampus. Significant positive correlations between
      cortical Abeta and pTau levels and circulating corticosterone indicate a
      potential role for GCs in mediating behavioral and biochemical changes observed
      after sleep restriction in a mouse model of AD. 

PMID- 23856326
TI  - Druggability of the enzymes of the non-mevalonate-pathway.
AB  - The non-mevalonate pathway constitutes a source of novel drug targets. This
      biosynthetic route is essential for pathogens but is absent in humans. Our
      systematic evaluation of the druggability of all enzymes provides a convenient
      way of selecting targets that should be most easily inhibited by small-molecule
      drugs. We found that not every target is equally druggable and we identified
      novel, druggable, potentially allosteric sites. These results should accelerate
      the development of anti-infective drugs with a novel mode of action, which are
      needed ever more urgently in light of the rapid emergence of drug-resistant
      strains. 

PMID- 23856325
TI  - NME1 suppression promotes growth, adhesion and implantation of endometrial
      stromal cells via Akt and MAPK/Erk1/2 signal pathways in the endometriotic
      milieu.
AB  - STUDY QUESTION: Is Nometastatic gene 23-H1 (NME1, also known as nm23-H1) involved
      in regulating the biological behavior of endometrial stromal cells (ESCs), and
      does it participate in the pathogenesis of endometriosis? SUMMARY ANSWER: NME1
      suppression induces ESC dysfunction in the endometriotic milieu. WHAT IS KNOWN
      ALREADY: NME1 is a wide-spectrum tumor metastasis suppressor gene that plays an
      important role in suppressing the invasion and metastasis of tumor cells. STUDY
      DESIGN, SIZE, DURATION: An in vitro investigation of the effect of NME1 on the
      proliferation, adhesion and invasion of eutopic ESCs from patients with
      endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary ESCs were
      prepared from 12 samples of ectopic endometrial tissue (6 peritoneal and 6
      ovarian lesions), 18 samples of eutopic endometrial tissues (16 from women with
      ovarian and 2 from women with pelvic endometriomas) and 12 samples of normal
      endometrial tissue from women without endometriosis, after the tissues had been
      analyzed histologically. The growth, invasiveness and adhesion of ESCs were
      studied by the 5-bromo-2'-deoxyuridine cell proliferation assay and by the
      Matrigel invasion and adhesion assay. Additionally, the effects of NME1 on the
      activation or expression of related regulatory proteins were investigated by in
      cell Western and flow cytometry assays. MAIN RESULTS AND THE ROLE OF CHANCE:
      Expression of NME1 in ESCs derived from eutopic or ectopic endometrium from women
      with endometriosis is lower than in ESCs from women without endometriosis.
      Estrogen could down-regulate NME1 expression in ESCs. Silencing NME1 in ESCs
      promoted the expression of proliferating cell nuclear antigen (PCNA), the anti
      apoptotic molecule, survivin, and the adhesion-related molecules, integrin beta1
      and integrin alphanubeta3. Silencing NME1 also stimulated ESC proliferation,
      adhesion and invasion but these effects were inhibited by MAPK/Erk and/or Akt
      blockers. LIMITATIONS, REASONS FOR CAUTION: Further studies are needed to examine
      the regulatory mechanism of estrogen on NME1 expression of ESCs. WIDER
      IMPLICATIONS OF THE FINDINGS: Abnormally low expression of NME1 in ESCs may be
      involved in the pathogenesis of endometriosis by up-regulating growth, adhesion
      and invasion of ESCs via activating the Akt and MAPK/Erk1/2 signal pathways.
      STUDY FUNDING/COMPETING INTEREST(S): This work was supported by National Natural
      Science Foundation of China (NSFC) (31270969, 31101064 and 81270677) and Program
      for ZhouXue of Fudan University. None of the authors has any conflict of interest
      to declare.

PMID- 23856327
TI  - Analysis of 10 years drug lifecycle management (LCM) activities in the Japanese
      market.
AB  - We investigated drug lifecycle management (LCM) activities in the Japanese market
      by examining new and updated approvals by the Pharmaceuticals and Medical Devices
      Agency (PMDA) between 2001 and 2010. PMDA gave a total of 726 approvals, of which
      263 and 463 were new and updated approvals, respectively. Approvals for new
      indication comprised of more than 60% of updated approvals regardless of chemical
      or biological entities, therapeutic area and the company nationality. The case
      study on anti-rheumatoid arthritis biologics showed that the addition of new
      indications accelerated their sales exponentially. Thus, the development of new
      indications is an effective LCM approach for creation of new values of existing
      drugs. 

PMID- 23856324
TI  - Thalamic physiology of intentional essential tremor is more like cerebellar
      tremor than postural essential tremor.
AB  - The neuronal physiological correlates of clinical heterogeneity in human
      essential tremor are unknown. We now test the hypothesis that thalamic neuronal
      and EMG activities during intention essential tremor are similar to those of the
      intention tremor which is characteristic of cerebellar lesions. Thalamic neuronal
      firing was studied in a cerebellar relay nucleus (ventral intermediate, Vim) and
      in a pallidal relay nucleus (ventral oral posterior, Vop) during stereotactic
      surgery for the treatment of tremor. Nine patients with essential tremor were
      divided clinically into two categories: one with a substantial component of
      tremor with intention (termed intention ET) and the other without (postural ET).
      These types of essential tremor were compared with patients having intention
      tremor plus other clinical signs of cerebellar disease (cerebellar tremor).
      Neurons in patients with either intention ET or cerebellar tremor had lower
      firing rates and lower spike*EMG coherence than those in patients with postural
      ET. Patients with intention ET had a lower spike*EMG phase lead than those with
      postural ET. Overall, thalamic activity measures of intention ET were different
      from postural ET but not apparently different from those of cerebellar tremor.
      One patient with the intention ET (number 4) had a good response to a left
      thalamotomy and then suffered a right cerebellar hemispheric infarct five years
      later. After the stroke the intention ET recurred, which is consistent with our
      hypothesis that intention ET is similar to that of the intention tremor which is
      characteristic of cerebellar lesions. 

PMID- 23856328
TI  - Role of the lpxM lipid A biosynthesis pathway gene in pathogenicity of avian
      pathogenic Escherichia coli strain E058 in a chicken infection model.
AB  - Lipopolysaccharide (LPS) is a major surface component of avian pathogenic
      Escherichia coli (APEC), and is a possible virulence factor in avian infections
      caused by this organism. The contribution of the lpxM gene, which encodes a
      myristoyl transferase that catalyzes the final step in lipid A biosynthesis, to
      the pathogenicity of APEC has not previously been assessed. In this study, an
      isogenic lpxM mutant, E058DeltalpxM, was constructed in APEC O2 strain E058 and
      then characterized. Structural analysis of lipid A from the parental strain and
      derived mutant showed that E058DeltalpxM lacked one myristoyl (C14:0) on its
      lipid A molecules. No differences were observed between the mutant and wild-type
      in a series of tests including growth rate in different broths and ability to
      survive in specific-pathogen-free chicken serum. However, the mutant showed
      significantly reduced invasion and intracellular survival in the avian macrophage
      HD11 cell line (P<0.05). Nitric oxide production reduction (P<0.05) and cytokine
      gene expression downregulation (P<0.05 or P<0.01) also showed in HD11 treated
      with E058DeltalpxM-derived LPS compared with that in cells treated with E058
      derived LPS at different times. Compared to the parental strain E058,
      E058DeltalpxM had a significant reduction in bacterial load in heart (P<0.01),
      liver (P<0.01), spleen (P<0.01), lung (P<0.05), and kidney (P<0.05) tissues. The
      histopathological lesions in visceral organs of birds challenged with the wild
      type strain were more severe than in birds infected with the mutant. However, the
      E058DeltalpxM mutant showed a similar sensitivity pattern to the parental strain
      following exposure to several hydrophobic reagents. These results indicate that
      the lpxM gene is important for the pathogenicity and biological activity of APEC
      strain E058.

PMID- 23856329
TI  - Decreased cardiotrophin-1 levels are associated with a lower risk of developing
      the metabolic syndrome in overweight/obese children after a weight loss program.
AB  - OBJECTIVE: Cardiotrophin-1 (CT-1) shares some similarities with other cytokines,
      and participates in the control of energy metabolism. Higher circulating levels
      are observed in obese humans, but little information is gathered in weight loss
      (WL) programs. Therefore, we aimed to investigate the association of serum CT-1
      levels with metabolic variables and the risk of developing metabolic syndrome
      (MetS) after a WL program in overweight/obese children. SUBJECTS AND METHODS:
      Forty-four overweight/obese children (mean age 11.5 y; 50% males) undergoing a 10
      week WL program were enrolled. Subjects were dichotomized at the median of Body
      Mass Index-Standard Deviation Score (BMI-SDS) change, as high and low responders
      after intervention. RESULTS: CT-1 levels were significantly reduced (-48 fmol/mL,
      p=0.043) in the high responder group after the WL program. They had significantly
      lower body weight (-3.7 kg, p<0.001), body fat mass (-8%, p<0.001), BMI-SDS (
      0.78, p<0.001) and waist circumference (-5.4 cm, p<0.001), and a significant
      improvement in lipid and glucose profiles (p<0.05). Interestingly, decreased CT-1
      levels significantly predicted changes in total cholesterol (41%) and LDL
      cholesterol (28%). Moreover, in our participants the lower the CT-1 levels, the
      higher the reduction in MetS risk components, after the 10-week intervention, (p
      ANCOVA=0.040, p-trend=0.024). CONCLUSION: We showed, for the first time, a
      reduction in serum CT-1 levels after a WL program and this decrease in CT-1 was
      strongly associated with a reduction in cholesterol levels and in MetS risk
      factors in overweight/obese children. Our findings may suggest that CT-1 could be
      an indirect marker for the diagnosis of MetS in this population.

PMID- 23856330
TI  - Impact of MenBvac, an outer membrane vesicle (OMV) vaccine, on the meningococcal
      carriage.
AB  - The aim of the study was to analyze the impact of MenBvac, an outer membrane
      vesicle (OMV) vaccine against P1.7,16 strains, on meningococcal carriage. During
      a B:14:P1.7,16/ST-32 outbreak in Normandy (France), children aged 1-7 years were
      randomly selected to participate in the study. Among the 1082 volunteers, there
      were 17 Neisseria meningitidis carriers (carriage rate of 1.57%). MenBvac
      vaccination appeared associated with lower carriage rate, i.e., 0.31% among the
      vaccinated children versus 2.10% among the non-vaccinated (p=0.03). The
      beneficial effect on carriage was observed regardless of the strain serogroup.
      OMV-vaccinated mice also showed reduction of bacterial acquisition of OMV-homolog
      and hererolog strains in respiratory pathways after intranasal challenge. These
      results suggest that meningococcal OMV-based vaccines reduce meningococcal
      carriage and may hence confer herd immunity. 

PMID- 23856331
TI  - Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in
      young and elderly adults: an observer-blind, randomized trial.
AB  - BACKGROUND: This study (NCT00979602) evaluated the immunogenicity and relative
      protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without
      AS03 (an alpha-tocopherol oil-in-water emulsion based Adjuvant System). METHODS:
      Four thousands and forty-eight healthy adults aged >= 18 years were randomized
      (1:1) to receive one dose of either the adjuvanted split virion (3.75 MUg
      hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15 MUg HA) vaccine.
      Hemagglutination inhibition [HI] antibody response was evaluated before
      vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines
      was evaluated during the entire study duration. RESULTS: At Day 21, both study
      vaccines induced HI immune responses meeting the US regulatory criteria in
      subjects 18-64 years (seroprotection rate [SPR]: 98.0% [97.1-98.6];
      seroconversion rate [SCR]: 89.7% [88.0-91.2] in the AS03-adjuvanted group; SPR:
      91.4% [89.9-92.8]; SCR: 74.6% [72.3-76.9] in the non-adjuvanted group) and >64
      years of age (SPR: 86.0% [82.5-89.0]; SCR: 75.3% [71.1-79.2] in the AS03
      adjuvanted group; SPR: 69.1% [64.6-73.3]; SCR: 56.7% [52.0-61.3] in the non
      adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean
      titers than the non-adjuvanted vaccine at all time points. At Month 6, only
      subjects 18-64 years of age from both vaccine groups still met the US regulatory
      criteria (SPR: 82.1% [80.0-84.1]; SCR: 62.3% [59.6-64.8] in the AS03-adjuvanted
      group; SPR: 75.3% [72.9-77.5]; SCR: 53.7% [51.0-56.4] in the non-adjuvanted
      group). Protective efficacy was not evaluated due to low number of RT-qPCR
      confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse
      events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted
      group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and
      7 in the non-adjuvanted group) were reported. CONCLUSION: A single dose of either
      adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI
      antibody levels against the A/California/7/2009 strain that persisted through
      Month 6 in the 18-64 years population.

PMID- 23856332
TI  - Vaccine effects and impact of vaccination programmes in post-licensure studies.
AB  - Once a vaccine is licensed and introduced in the population, post-licensure
      studies are required to measure vaccine effectiveness and impact of vaccination
      programmes on the population at large. However, confusion still prevails around
      these concepts, making it difficult to discern which effects are measured in such
      studies and how their findings should be interpreted. We review from the public
      health evaluation perspective the effects of vaccine-related exposures, describe
      the methods used to measure them and their assumptions. We distinguish effects
      due to exposure to individual vaccination from those due to exposure to a
      vaccination programme, as the latter depends on vaccine coverage, other
      population factors and includes indirect effects as well. Vaccine (direct)
      effectiveness is estimated by comparing vaccinated and unvaccinated individuals
      exposed to the same vaccination programme. The impact of a vaccination programme,
      defined here as the population prevented fraction when exposure is the programme,
      is measured by comparing populations with and without a vaccination programme,
      most commonly the same population before and after vaccination. These designs are
      based on a number of assumptions for valid inference. In particular, they assume
      that vaccinees and non-vaccinees do not differ in terms of susceptibility and
      exposure to the disease or in ascertainment of vaccination and disease status. In
      pre and post-vaccination design, the population is assumed to have similar
      baseline transmission, case detection and reporting, risk factors and medical
      practices in both periods. These principles are frequently violated in post
      licensure studies. Potential confounding and biases must be minimized in study
      design and analyses, or taken into account during result interpretation. It is
      also essential to define which exposure is evaluated (individual vaccination or
      vaccination programme) and which effect is measured. This may help decision
      makers clarify which type of study is needed and how to interpret the results. 

PMID- 23856333
TI  - The genetically modified suilysin, rSLY(P353L), provides a candidate vaccine that
      suppresses proinflammatory response and reduces fatality following infection with
      Streptococcus suis.
AB  - Streptococcus suis is a persistent global hazard in the swine industry and an
      emerging threat to public health. The high mortality in China following outbreaks
      of streptococcal toxic shock syndrome (STSS) underscores the urgency for
      effective prevention. A limited understanding of the pathogenesis of S. suis in
      STSS may explain the lack of biological products for prevention. Suilysin (SLY)
      is an important virulence factor in the pathogenesis of S. suis. To identify a
      candidate vaccine for S. suis-induced STSS, we constructed a recombinant non
      hemolytic mutant of SLY that has hemagglutination activity, rSLY(P353L), and
      evaluated its ability to induce inflammatory response and prevent fatal S. suis
      infection in mice. The rSLY(P353L) mutant, as compared with hemolytic rSLY,
      elicited lower levels of IL-6, KC and IL-10 at 3h and 5h post-treatment (p<0.05),
      indicating that hemolytic activity is associated with rSLY-mediated inflammation.
      Furthermore, passive immunization with anti-SLY(P353L) antisera protected mice
      from acute death after infection with S. suis SC84 (p<0.05). Effects were not due
      to protection against tissue damage, as S. suis SC84 caused no detectable
      histopathological lesions in mice within 24h. However, immunization with
      rSLY(P353L) caused significantly reduced levels of KC and IL-1beta at 6 and 9h
      post-challenge and IL-6 at 9h post-challenge (p<0.05). In conclusion, rSLY(P353L)
      may provide a potential vaccine for protection against S. suis-induced STSS due
      to its reduction in proinflammatory response early in S. suis infection.

PMID- 23856334
TI  - Protein aggregation propensity is a crucial determinant of intracellular
      inclusion formation and quality control degradation.
AB  - Protein aggregation is linked to many pathological conditions, including several
      neurodegenerative diseases. The aggregation propensities of proteins are thought
      to be controlled to a large extent by the physicochemical properties encoded in
      the primary sequence. We have previously exploited a set of amyloid beta peptide
      (Abeta42) variants exhibiting a continuous gradient of intrinsic aggregation
      propensities to demonstrate that this rule applies in vivo in bacteria. In the
      present work we have characterized the behavior of these Abeta42 mutants when
      expressed in yeast. In contrast to bacteria, the intrinsic aggregation propensity
      is gated by yeast, in such a way that this property correlates with the formation
      of intracellular inclusions only above a specific aggregation threshold. Proteins
      displaying solubility levels above this threshold escape the inclusion formation
      pathway. In addition, the most aggregation-prone variants are selectively cleared
      by the yeast quality control degradation machinery. Thus, both inclusion
      formation and proteolysis target the same aggregation-prone variants and
      cooperate to minimize the presence of these potentially dangerous species in the
      cytosol. The demonstration that sorting to these pathways in eukaryotes is
      strongly influenced by protein primary sequence should facilitate the development
      of rational approaches to predict and hopefully prevent in vivo protein
      deposition. 

PMID- 23856336
TI  - Walking more slowly than with normal velocity: The influence on trunk and pelvis
      kinematics in young and older healthy persons.
AB  - BACKGROUND: Few studies have addressed trunk and pelvis movements during gait,
      although they play an important role in gait control. The aim of this study was
      to compare trunk and pelvis kinematics between slower walking (1, 2, 3, 4kmph)
      and normal walking (5kmph), and between healthy adults who were young (n=15, 20
      30years) and older (n=17, 50-60years). METHODS: After 4min of treadmill walking,
      the 3-dimensional trunk and pelvis kinematics was measured (Polhemus LibertyTM,
      250Hz). A repeated measures ANOVA with simple contrasts was used to look for
      differences between the velocity conditions of walking and independent t-testing
      for comparison between the age groups (significance level: 5%, SPSS20). FINDINGS:
      Walking more slowly than with normal velocity induces (1) a decrease in vertical
      center of mass of the trunk displacement, trunk lateral flexion and axial
      rotation and pelvis lateral and antero-posterior tilting, and (2) an increase in
      lateral and antero-posterior center of mass of the trunk displacement. Compared
      to young persons, older persons show: (1) larger pelvis axial rotations and trunk
      lateral and antero-posterior movements, and (2) smaller pelvis lateral tilting
      and trunk vertical movements and rotations. INTERPRETATION: The literature
      reports that patients often walk slowly and that older persons show different
      gait patterns compared to young persons. This study shows that there are changes
      in trunk and pelvis kinematics (1) when walking more slowly than with normal
      velocity and (2) in older persons compared to young persons. These data could be
      taken into account in gait rehabilitation.

PMID- 23856337
TI  - Is it time for plakoglobin immune-histochemical diagnostic test for
      arrhythmogenic cardiomyopathy in the routine pathology practice?

PMID- 23856335
TI  - Overcoming barriers and thresholds - signaling of oligomeric Abeta through the
      prion protein to Fyn.
AB  - Evidence has been mounting for an involvement of the prion protein (PrP) in a
      molecular pathway assumed to play a critical role in the etiology of Alzheimer
      disease. A currently popular model sees oligomeric amyloid beta (oAbeta) peptides
      bind directly to PrP to emanate a signal that causes activation of the
      cytoplasmic tyrosine kinase Fyn, an essential player in a cascade of events that
      ultimately leads to NMDA receptor-mediated excitotoxicity and hyper
      phosphorylation of tau. The model does not reveal, however, how extracellular
      binding of oAbeta to PrP is communicated across the plasma membrane barrier to
      affect activation of Fyn. A scenario whereby PrP may adapt a transmembrane
      topology to affect Fyn activation in the absence of additional partners is
      currently not supported by evidence. A survey of known candidate PrP interactors
      leads to a small number of molecules that are known to acquire a transmembrane
      topology and understood to contribute to Fyn activation. Because multiple
      signaling pathways converge onto Fyn, a realistic model needs to take into
      account a reality of Fyn acting as a hub that integrates signals from multiple
      inhibitory and activating effectors. To clarify the role of PrP in oAbeta
      dependent excitotoxicity, future studies may need to incorporate experimental
      designs that can probe the contributions of Fyn modulator pathways and rely on
      analogous readouts, rather than threshold effects, known to underlie excitotoxic
      signaling. 

PMID- 23856338
TI  - Reference interval for lipid profile in North Indian population from Rajasthan
      according to various partitioning criteria.
AB  - OBJECTIVE: Lipid profile parameters are influenced by various factors like age,
      ethnicity, diet, genetic and gender differences hence it is essential to
      establish reference range of the values of serum lipids for a given population in
      India. We have planned this study to evaluate the reference values of lipid
      profile of a North Indian population according to the guidelines of the National
      Cholesterol Education Program (NCEP) of the USA. DESIGN AND METHODS: The present
      study was conducted on 2021 apparently healthy individuals of North Indian origin
      ranging in age from 15 to 60 years, who were selected randomly using defined
      criteria. Fasting samples were analyzed for total cholesterol, triglyceride, HDL
      C and LDL-C. Data were analyzed for middle 95th percentile (2.5th-97.5th
      percentile), median and 95% confidence interval using SPSS software package
      version 10.0. RESULTS: No substantial difference could be observed between male
      and female and vegetarian and non-vegetarian, in cholesterol, triglyceride and
      LDL-C levels. However HDL-C reported higher limit in female as compared to male
      (33-64 vs 32-58 mg/dl). Similarly upper limit of HDL-C in vegetarians were higher
      than non-vegetarian (value 32.8-64.92 vs 30.72-58.10mg/dl). Median value for
      cholesterol, triglyceride, LDL-C progressively increased in different age groups
      (<20, 20-40 and 41-60 years). No marked difference was observed in reference
      interval of these parameters in rural and urban populations. CONCLUSION: It can
      be suggested that lipid values obtained in this study can be used as the
      reference value, based on which clinical correlation can be made.

PMID- 23856339
TI  - The broader context of antibiotic resistance: zinc feed supplementation of
      piglets increases the proportion of multi-resistant Escherichia coli in vivo.
AB  - Following the Europe-wide ban of antimicrobial growth promoters, feed
      supplementation with zinc has increased in livestock breeding. In addition to
      possible beneficial effects on animal health, feed supplementation with heavy
      metals is known to influence the gut microbiota and might promote the spread of
      antimicrobial resistance via co-selection or other mechanisms. As Escherichia
      coli is among the most important pathogens in pig production and often displays
      multi-resistant phenotypes, we set out to investigate the influence of zinc feed
      additives on the composition of the E. coli populations in vivo focusing on
      phylogenetic diversity and antimicrobial resistance. In a piglet feeding trial,
      E. coli were isolated from ileum and colon digesta of high dose zinc-supplemented
      (2500ppm) and background dose (50ppm) piglets (control group). The E. coli
      population was characterized via pulsed-field gel electrophoresis (PFGE) and
      multi-locus sequence typing (MLST) for the determination of the phylogenetic
      background. Phenotypic resistance screening via agar disk diffusion and minimum
      inhibitory concentration testing was followed by detection of resistance genes
      for selected clones. We observed a higher diversity of E. coli clones in animals
      supplemented with zinc compared to the background control group. The proportion
      of multi-resistant E. coli was significantly increased in the zinc group compared
      to the control group (18.6% vs. 0%). For several subclones present both in the
      feeding and the control group we detected up to three additional phenotypic and
      genotypic resistances in the subclones from the zinc feeding group.
      Characterization of these subclones suggests an increase in antimicrobial
      resistance due to influences on plasmid uptake by zinc supplementation,
      questioning the reasonability of zinc feed additives as a result of the ban of
      antimicrobial growth promoters. 

PMID- 23856340
TI  - Streptococcus tigurinus is highly virulent in a rat model of experimental
      endocarditis.
AB  - Streptococcus tigurinus is responsible for systemic infections in humans
      including infective endocarditis. We investigated whether the invasive trait of
      S. tigurinus in humans correlated with an increased ability to induce IE in rats.
      Rats with catheter-induced aortic vegetations were inoculated with 104 CFU/ml of
      either of four S. tigurinus strains AZ_3a(T), AZ_4a, AZ_8 and AZ_14, isolated
      from patients with infective endocarditis or with the well known IE pathogen
      Streptococcus gordonii (Challis). Aortic infection was assessed after 24 h. S.
      tigurinus AZ_3a(T), AZ_4a and AZ_14 produced endocarditis in >=80% of rats
      whereas S. gordonii produced endocarditis in only 33% of animals (P<0.05). S.
      tigurinus AZ_8 caused vegetation infection in 56% of the animals. The capacity of
      S. tigurinus to induce aortic infection was not related to their ability to bind
      extracellular matrix proteins (fibrinogen, fibronectin or collagen) or to trigger
      platelet aggregation. However, all S. tigurinus isolates showed an enhanced
      resistance to phagocytosis by macrophages and two of them had an increased
      ability to enter endothelial cells, key attributes of invasive streptococcal
      species.

PMID- 23856341
TI  - The B1-cell subpopulation is diminished in patients with relapsing-remitting
      multiple sclerosis.
AB  - B cell subsets in newly diagnosed untreated, relapsing-remitting multiple
      sclerosis (MS) patients were examined. The fraction of CD20(+) B cells was
      significantly increased in MS. Among subsets of B cells, MS patients had
      increased frequency of naive cells, but reduced frequency of memory and B1 cells.
      The frequencies of B1 cells were inversely correlated with the time since last
      attack. B1 cells resembled the phenotype of either lymphocytes (CD11b(-) B1
      cells) or monocytes (CD11b(+) B1 cells) and a small fraction of cells was
      CD3(+)CD20(+) by confocal microscopy. 

PMID- 23856342
TI  - Transcriptome analysis reveals novel genes potentially involved in photoperiodic
      tuberization in potato.
AB  - Potato microtuber produced in vitro provides a model system to investigate
      photoperiod-dependent tuberization. However, the genes associated with potato
      tuberization remain to be elucidated. The present research involved three potato
      clones with distinct tuberization response to changes of photoperiod. Digital
      Gene Expression (DGE) Tag Profiling analysis of the short-day-sensitive clone
      identified 2218 genes that were regulated by day length. Both GO and KEGG pathway
      analysis provided insights into predominant biological processes and pathways,
      and enabled the selection of 56 genes associated with circadian rhythmicity,
      signal transduction, and development. Quantitative transcriptional analysis in
      the selected clones revealed 5 genes potentially associated with photoperiodic
      tuberization, which were predicted to encode a DOF protein, a blue light
      receptor, a lectin, a syntaxin-like protein, and a protein with unknown function.
      Our results strongly suggest that potato tuberization may be largely controlled
      by the homologs of genes shown to regulate flowering time in other plants. 

PMID- 23856344
TI  - Effect of the precrack preparation with an ultrasonic instrument on the ceramic
      bracket removal.
AB  - BACKGROUND/PURPOSE: In terms of fracture mechanics, a precrack preparation may
      facilitate the propagation of a break through the expected fracture plane during
      the bracket debonding process. The purpose of this study was to evaluate the
      effect of an ultrasonic precrack preparation on the debonding force and failure
      modes of ceramic bracket removal. METHODS: Eighty extracted premolars were
      assigned to four groups: Inspire, precrack Inspire, Clarity, and precrack Clarity
      groups, with each group containing 20 teeth. The precrack preparations were made
      at the mesial gingival line angle of Inspire brackets and on the mesial side of
      Clarity brackets with an ultrasonic tip. Debonding force, failure modes, and
      bracket breakage score were measured and recorded. Fracture surfaces after
      bracket debonding were observed with scanning electron microscopy (SEM). RESULTS:
      We found that the ultrasonic precrack preparation could significantly decrease
      the average debonding force and the mean bracket breakage scores of both kinds of
      ceramic brackets. After bracket debonding, 80% of brackets in the precrack
      Inspire group and 100% of brackets in the precrack Clarity group showed no
      bracket failure. However, only 25% of brackets in the Inspire group and 75% of
      brackets in the Clarity group showed no bracket failure. SEM micrographs showed a
      precrack notch at the adhesive resin after precrack preparation, and no enamel
      damage was noted after the bracket debonding. CONCLUSION: The ultrasonic precrack
      preparation can significantly decrease the debonding force and may guide the
      bracket debonding through a favorable fracture plane without damage to either the
      bracket or the enamel.

PMID- 23856345
TI  - Focal osteoporotic marrow defect of the maxilla.

PMID- 23856343
TI  - Characterization of the two intracellular lipases of Y. lipolytica encoded by
      TGL3 and TGL4 genes: new insights into the role of intracellular lipases and
      lipid body organisation.
AB  - Eukaryotes store lipids in a specialised organelle, the lipid body (LB), mainly
      as triglycerides (TAGs). Both the rates of synthesis and degradation contribute
      to the control of the accumulation of TAGs. The synthesis of TAGs in yeasts has
      been well documented, especially in the model yeast Saccharomyces cerevisiae and
      in the oleaginous yeast Yarrowia lipolytica. However, descriptions of the
      processes involved in TAG degradation are more scarce and mostly for S.
      cerevisiae. Here, we report the characterisation of two Y. lipolytica genes,
      YlTGL3 and YlTGL4, encoding intracellular lipases involved in TAG degradation.
      The two proteins are localised in lipid bodies, and YlTgl4 was mainly found at
      the interface between LBs. Surprisingly, the spatial organisation of YlTgl3 and
      YlTgl4 depends on the culture medium and on the physiological phase of the cell.
      Inactivation of one or both genes doubles the lipid accumulation capacity of Y.
      lipolytica, increasing the cell's capacity to accumulate TAGs. The amino acid
      sequence of YlTgl4 contains the consensus sequence motif (G/A)XSXG, typical of
      serine hydrolases, whereas YlTgl3 does not. Single and double mutants are unable
      to degrade TAGs, and higher expression of YlTgl4 correlates with TAG degradation.
      Therefore, we propose that YlTgl4 is the main lipase responsible for TAG
      degradation and that YlTgl3 may act as a positive regulator of YlTgl4 rather than
      a functional lipase. Thus, contrary to S. cerevisiae, Y. lipolytica possesses two
      intracellular lipases with distinct roles and with distinct localisations in the
      LB. 

PMID- 23856346
TI  - Algorithmic approach by endobronchial ultrasound-guided transbronchial needle
      aspiration for isolated intrathoracic lymphadenopathy: a study in a tuberculosis
      endemic country.
AB  - BACKGROUND/PURPOSE: Isolated intrathoracic lymphadenopathy (IT-LAP) is clinically
      challenging because of the difficult anatomic location and wide range of
      associated diseases, including tuberculosis (TB). Although sampling via
      endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for
      histopathology is a major development, there is still room for improvement. This
      study aimed to investigate an algorithmic approach driven by EBUS-TBNA and
      conventional bronchoscopy to streamline the management of IT-LAP. METHODS: Eighty
      three prospectively enrolled patients with IT-LAP were subjected to an EBUS-TBNA
      diagnostic panel test (histopathology, cytology, and microbiology) and underwent
      conventional bronchoscopy for bronchoalveolar lavage. The results were structured
      into an algorithmic approach to direct patient treatment, workup, or follow-up.
      RESULTS: The diagnostic yields of EBUS-TBNA based on histopathology were similar
      for each disease entity: 77.8% for malignancy, 70.0% for TB, 75.0% for
      sarcoidosis, 80.0% for anthracosis, and 70.0% for lymphoid hyperplasia (p =
      0.96). The incidence of malignancy was 10.8% for total IT-LAP patients, and 12.0%
      and 33.7% for patients with TB and sarcoidosis, respectively. Thirty-five (42.2%)
      patients were symptomatic. The leading diagnosis was sarcoidosis (60%), followed
      by TB (20%), malignancy (11.4%), lymphoid hyperplasia (5.7%), and anthracosis
      (2.9%). By logistic regression analysis, granulomatous disease (odds ratio:
      13.45; 95% confidence interval: 4.45-40.67, p < 0.001) was an independent
      predictor of symptoms. Seven (8.4%) and three (3.6%) IT-LAP patients diagnosed
      active TB and suggestive of TB with household contact history, respectively, were
      all placed on anti-TB treatment. CONCLUSION: The algorithmic approach streamlines
      patient management. It enables early detection of malignancy, correctly places
      nonmalignant patients on an appropriate treatment regimen, and particularly
      identifies candidates at high risk of TB reactivation for anti-TB
      chemoprophylaxis.

PMID- 23856347
TI  - Ergonomic principles and techniques in facilitating advanced laparoendoscopic
      single site (LESS) urinary tract reconstruction with conventional laparoscopic
      instruments.
AB  - BACKGROUND/PURPOSE: The technical and ergonomic details of laparoendoscopic
      single site (LESS) reconstruction have not been reported. In this study, we
      explored the feasibility and safety of performing advanced LESS upper urinary
      tract reconstruction with conventional laparoscopic instruments. METHODS: Between
      September 2010 and March 2011, we retrospectively reviewed prospectively
      collected data from five patients who underwent LESS urinary tract
      reconstruction. The LESS reconstruction included pyeloureterostomy (N = 1),
      dismembered pyeloplasty (N = 2), ureteroneocystostomy (N = 1), and ureteroplasty
      for bifid blind ending ureter (N = 1). The perioperative and postoperative
      parameters were collected for analysis. The ergonomic principles and techniques
      are detailed. RESULTS: All reconstructive LESS procedures were completed
      successfully without open conversion or laparoscopic conversion. Ancillary ports
      or ancillary instruments were not applied in any of the patients. The mean
      patient age was 40.4 years. The mean operative time was 213 +/- 69 minutes, the
      estimated blood loss ranged from minimal to 50 mL, and the mean hospital stay was
      4.4 +/- 4 days. No operation-related complication occurred. CONCLUSION: Based on
      our ergonomic principles and suturing/knotting techniques, conventional
      laparoscopic instruments are feasible and safe for LESS urinary reconstructive
      procedures.

PMID- 23856348
TI  - On the study of the transmission networks of blood parasites from SW Spain:
      diversity of avian haemosporidians in the biting midge Culicoides circumscriptus
      and wild birds.
AB  - BACKGROUND: Blood-sucking flying insects play a key role in the transmission of
      pathogens of vector-borne diseases. However, at least for the case of avian
      malaria parasites, the vast majority of studies focus on the interaction between
      parasites and vertebrate hosts, but there is a lack of information regarding the
      interaction between the parasites and the insect vectors. Here, we identified the
      presence of malaria and malaria-like parasite lineages harbored by the potential
      vector Culicoides circumscriptus (Kieffer). Also, we identified some nodes of the
      transmission network connecting parasite lineages, potential insect vectors and
      avian hosts by comparing Haemoproteus and Plasmodium lineages isolated from
      insects with those infecting wild birds in this and previous studies. METHODS:
      Using a molecular approach, we analysed the presence of blood parasites in a
      total of 97 biting midges trapped in the Donana National Park (SW Spain) and
      surrounding areas. Also, 123 blood samples from 11 bird species were analyzed for
      the presence of blood parasite infections. Blood parasites Haemoproteus and
      Plasmodium were identified by amplification of a 478 bp fragment of the
      mitochondrial cytochrome b gen. RESULTS: Thirteen biting midges harboured blood
      parasites including six Haemoproteus and two Plasmodium lineages, supporting the
      potential role of these insects on parasite transmission. Moreover, ten (8.1%)
      birds carried blood parasites. Seven Plasmodium and one Haemoproteus lineages
      were isolated from birds. Overall, six new Haemoproteus lineages were described
      in this study. Also, we identified the transmission networks of some blood
      parasites. Two Haemoproteus lineages, hCIRCUM03 and GAGLA03, were identical to
      those isolated from Corvus monedula in southern Spain and Garrulus glandarius in
      Bulgaria, respectively. Furthermore, the new Haemoproteus lineage hCIRCUM05
      showed a 99% similarity with a lineage found infecting captive penguins in Japan.
      CONCLUSIONS: The comparison of the parasite lineages isolated in this study with
      those previously found infecting birds allowed us to identify some potential
      nodes in the transmission network of avian blood parasite lineages. These results
      highlight the complexity of the transmission networks of blood parasites in the
      wild that may involve a high diversity of susceptible birds and insect vectors.

PMID- 23856349
TI  - Early prediction of cerebral palsy after neonatal intensive care using motor
      development trajectories in infancy.
AB  - Neonatal intensive care unit (NICU) patients are at high risk for developmental
      disabilities such as cerebral palsy (CP). Early identification of CP is essential
      to effective rehabilitation, but diagnosis is often delayed, especially in
      preterm infants. We hypothesized that through the longitudinal evaluation of
      motor trajectories in the NICU follow-up clinic, we could distinguish infants who
      develop CP by 3 years of age. STUDY DESIGN AND SUBJECTS: This was a retrospective
      study of 606 patients in the NICU Follow-up Clinic at Vanderbilt University with
      birth weight < 1500g or a diagnosis of hypoxic ischemic encephalopathy. OUTCOMES
      MEASURES: Assessments included neurologic exams, the Developmental Assessment of
      Young Children (DAYC), the Bayley Scales of Infant Development (BSID) and the
      Gross Motor Function Classification Scale. RESULTS: A decrease in DAYC scores
      between 6 and 12 months was present in preterm and term infants later diagnosed
      with CP, but not in children without CP (-23 vs. +1.5, p<0.001). DAYC score
      decreases in infancy were highly predictive of later CP (p<0.001). BSID scores
      quantified severe motor delays but did not add to prediction of CP diagnosis.
      CONCLUSION: Standardized assessments of motor milestones quantitatively predict
      the risk of CP in former NICU patients by 12 months, allowing for timely
      diagnosis, counseling and therapy in high-risk infants.

PMID- 23856350
TI  - Effect of orthodontic treatment on lip position.
AB  - Does an advanced or retracted position of the upper and lower incisors lead to
      modifications in lip position? The aim of our study was to evaluate modifications
      in lip position following orthodontic treatments. MATERIAL AND METHODS: This
      study concerned 100 patients who underwent treatment in the dento-facial
      orthopedic unit in Casablanca. Profile headfilms at the start and at the end of
      orthodontic treatment were compared using Frapier's analysis. The Student test
      was applied to evaluate the variations in the cephalometric measurements.
      RESULTS: We noted a non-significant increase in the nasolabial angle (P = 0.274),
      a significant decrease in the sagittal position of the lower vermillion border
      (PsVei) (P < 0.001) and the sagittal position of the soft-tissue supramentale
      (PsSmc) (P < 0.001), and a significant increase in the vertical position of the
      soft-tissue menton (PvMec) (P = 0.035). CONCLUSION: The results of this study
      demonstrate marked improvements in the situation of soft tissues. We suggest
      further investigation to throw light on the relationship between tooth movement
      and soft tissue, increasing the size of the sample and taking growth into
      account.

PMID- 23856352
TI  - Environmental concentrations of engineered nanomaterials: review of modeling and
      analytical studies.
AB  - Scientific consensus predicts that the worldwide use of engineered nanomaterials
      (ENM) leads to their release into the environment. We reviewed the available
      literature concerning environmental concentrations of six ENMs (TiO2, ZnO, Ag,
      fullerenes, CNT and CeO2) in surface waters, wastewater treatment plant
      effluents, biosolids, sediments, soils and air. Presently, a dozen modeling
      studies provide environmental concentrations for ENM and a handful of analytical
      works can be used as basis for a preliminary validation. There are still major
      knowledge gaps (e.g. on ENM production, application and release) that affect the
      modeled values, but over all an agreement on the order of magnitude of the
      environmental concentrations can be reached. True validation of the modeled
      values is difficult because trace analytical methods that are specific for ENM
      detection and quantification are not available. The modeled and measured results
      are not always comparable due to the different forms and sizes of particles that
      these two approaches target.

PMID- 23856354
TI  - Similarities and differences between interference from stimulus position and from
      direction of an arrow: behavioral and event-related potential measures.
AB  - Studies with stimulus-response compatibility (SRC) tasks used the stimulus
      position (SRC-p) and/or the direction indicated by a central arrow (SRC-d) as
      irrelevant dimensions. Despite behavioral differences revealed by the
      distributional analysis (DA), both interferences were established at similar loci
      on the basis of modulations in the lateralized readiness potential (LRP) and P3b
      components. Consequently, similar underlying mechanisms were proposed for both
      interferences. However, comparison of motor processes associated with each task
      is problematical because each involves different components. In addition,
      previous studies have frequently used different proportions of trials between
      conditions, which complicate interpretation of the results because the stimulus
      probability may modulate P3b. Taking these problems into account, the present
      study investigated the effects of interference in SRC-p and SRC-d tasks, in which
      the participants responded to the color of a stimulus while ignoring the position
      and the direction indicated by a central arrow, respectively. The interference
      was greater in the SRC-p than in the SRC-d task. The DA showed that stimulus
      position affected the performance more quickly than the direction of the arrow.
      The P3b latency was longer and the P3b amplitude was smaller when stimulus
      position was incompatible. However, no differences in P3b were found in the SRC-d
      task. Moreover, both types of interference affected response-related processes
      (LRP-r) similarly. Therefore, the stimulus position and the direction indicated
      by the stimulus may share a common locus of interference (response execution),
      but only stimulus position affects P3b component, which constitutes a link
      between stimulus evaluation and the response selection. 

PMID- 23856353
TI  - Olfaction in the psychosis prodrome: electrophysiological and behavioral measures
      of odor detection.
AB  - Smell identification deficits (SIDs) are relatively specific to schizophrenia and
      its negative symptoms, and may predict transition to psychosis in clinical high
      risk (CHR) individuals. Moreover, event-related potentials (ERPs) to odors are
      reduced in schizophrenia. This study examined whether CHR patients show SIDs and
      abnormal olfactory N1 and P2 potentials. ERPs (49 channels) were recorded from 21
      CHR and 20 healthy participants (13 males/group; ages 13-27 years) during an odor
      detection task using three concentrations of hydrogen sulfide (H2S) or blank air
      presented unilaterally by a constant-flow olfactometer. Neuronal generator
      patterns underlying olfactory ERPs were identified and measured by principal
      components analysis (unrestricted Varimax) of reference-free current source
      densities (CSD). Replicating previous findings, CSD waveforms to H2S stimuli were
      characterized by an early N1 sink (345 ms, lateral-temporal) and a late P2 source
      (600 ms, mid-frontocentroparietal). N1 and P2 varied monotonically with odor
      intensity (strong > medium > weak) and did not differ across groups. Patients and
      controls also showed comparable odor detection and had normal odor identification
      and thresholds (Sniffin' Sticks). However, olfactory ERPs strongly reflected
      differences in odor intensity and detection in controls, but these associations
      were substantially weaker in patients. Moreover, severity of negative symptoms in
      patients was associated with reduced olfactory ERPs and poorer odor detection,
      identification and thresholds. Three patients who developed psychosis had poorer
      odor detection and thresholds, and marked reductions of N1 and P2. Thus, despite
      the lack of overall group differences, olfactory measures may be of utility in
      predicting transition to psychosis among CHR patients.

PMID- 23856355
TI  - One hundred consecutive patients treated with magnetic sphincter augmentation for
      gastroesophageal reflux disease: 6 years of clinical experience from a single
      center.
AB  - BACKGROUND: This study was undertaken to evaluate our clinical experience during
      a 6-year period with an implantable device that augments the lower esophageal
      sphincter for gastroesophageal reflux disease (GERD). The device uses magnetic
      sphincter augmentation (MSA) to strengthen the antireflux barrier. STUDY DESIGN:
      In a single-center, prospective case series, 100 consecutive patients underwent
      laparoscopic MSA for GERD between March 2007 and February 2012. Clinical outcomes
      for each patient were tracked post implantation and compared with presurgical
      data for esophageal pH measurements, symptom scores, and proton pump inhibitor
      (PPI) use. RESULTS: Median implant duration was 3 years (range 378 days to 6
      years). Median total acid exposure time was reduced from 8.0% before implant to
      3.2% post implant (p < 0.001). The median GERD Health Related Quality of Life
      score at baseline was 16 on PPIs and 24 off PPIs and improved to a score of 2 (p
      < 0.001). Freedom from daily dependence on PPIs was achieved in 85% of patients.
      There have been no long-term complications, such as device migrations or
      erosions. Three patients had the device laparoscopically removed for persistent
      GERD, odynophagia, or dysphagia, with subsequent resolution of symptoms.
      CONCLUSIONS: Magnetic sphincter augmentation for GERD in clinical practice
      provides safe and long-term reduction of esophageal acid exposure, substantial
      symptom improvement, and elimination of daily PPI use. For candidates of
      antireflux surgery who have been carefully evaluated before surgery to confirm
      indication for MSA, MSA has become a standard treatment at our institution
      because control of reflux symptoms and pH normalization can be achieved with
      minimal side effects and preservation of gastric anatomy.

PMID- 23856359
TI  - High prevalence of osteoporosis in patients with chronic pancreatitis: a
      systematic review and meta-analysis.
AB  - BACKGROUND & AIMS: Patients with chronic pancreatitis may be at high risk for
      osteoporosis and osteopenia. We performed a systematic review and meta-analysis
      to determine the prevalence of osteoporosis and osteopenia in patients with
      chronic pancreatitis. METHODS: Articles were identified from MEDLINE, EMBASE, and
      SCOPUS databases (through October 2012) and a manual search of the literature.
      The primary outcome measure was bone density, measured by dual-energy X-ray
      absorptiometry (T-score or Z-score). When available, data on the prevalence of
      osteopenia, bone mineral density, and bone mineral content also were recorded.
      RESULTS: Ten studies including 513 patients were eligible for inclusion. Based on
      a random-effects model, the pooled prevalence rate for osteoporosis among
      patients with chronic pancreatitis was 23.4% (95% confidence interval, 16.6
      32.0). The pooled prevalence for osteopenia was 39.8% (95% confidence interval,
      29.1-51.6). The pooled prevalence rate for either osteoporosis or osteopenia was
      65% (95% confidence interval, 54.7-74.0). CONCLUSIONS: Based on meta-analysis,
      almost 1 of 4 patients with chronic pancreatitis have osteoporosis, and almost
      two-thirds of patients have either osteoporosis or osteopenia. Osteoporosis and
      osteopenia are underappreciated sources of morbidity in patients with chronic
      pancreatitis. Bone health management guidelines are urgently required in patients
      with chronic pancreatitis.

PMID- 23856358
TI  - Long-term risk of acute diverticulitis among patients with incidental
      diverticulosis found during colonoscopy.
AB  - BACKGROUND & AIMS: Colonic diverticulosis is the most common finding during
      routine colonoscopy, and patients often question the significance of these
      lesions. Guidelines state that these patients have a 10% to 25% lifetime risk of
      developing acute diverticulitis. However, this value was determined based on
      limited data, collected before population-based colonoscopy, so the true number
      of cases of diverticulosis was not known. We measured the long-term risk of acute
      diverticulitis among patients with confirmed diverticulosis discovered
      incidentally on colonoscopy. METHODS: We performed a retrospective study using
      administrative and clinical data from the Veterans Affairs Greater Los Angeles
      Healthcare System, collecting data on patients who underwent colonoscopies from
      January 1996 through January 2011. We identified patients diagnosed with
      diverticulosis, determined incidence rates per 1000 patient-years, and analyzed a
      subgroup of patients with rigorously defined events confirmed by imaging or
      surgery. We used a Cox proportional hazards model to identify factors associated
      with the development of diverticulitis. RESULTS: We identified 2222 patients with
      baseline diverticulosis. Over an 11-year follow-up period, 95 patients developed
      diverticulitis (4.3%; 6 per 1000 patient-years); of these, 23 met the rigorous
      definition of diverticulitis (1%; 1.5 per 1000 patient-years). The median time-to
      event was 7.1 years. Each additional decade of age at time of diagnosis reduced
      the risk for diverticulitis by 24% (hazard ratio, 0.76; 95% confidence interval,
      0.6-0.9). CONCLUSIONS: Based on a study of the Veterans Affairs Greater Los
      Angeles Healthcare System, only about 4% of patients with diverticulosis develop
      acute diverticulitis, contradicting the common belief that diverticulosis has a
      high rate of progression. We also found that younger patients have a higher risk
      of diverticulitis, with risk increasing per year of life. These results can help
      inform patients with diverticulosis about their risk of developing acute
      diverticulitis.

PMID- 23856357
TI  - Computational modelling of bovine ovarian follicle development.
AB  - BACKGROUND: The development of ovarian follicles hinges on the timely exposure to
      the appropriate combination of hormones. Follicle stimulating hormone (FSH) and
      luteinizing hormone (LH) are both produced in the pituitary gland and are
      transported via the blood circulation to the thecal layer surrounding the
      follicle. From there both hormones are transported into the follicle by
      diffusion. FSH-receptors are expressed mainly in the granulosa while LH-receptors
      are expressed in a gradient with highest expression in the theca. How this
      spatial organization is achieved is not known. Equally it is not understood
      whether LH and FSH trigger distinct signalling programs or whether the distinct
      spatial localization of their G-protein coupled receptors is sufficient to convey
      their distinct biological function. RESULTS: We have developed a data-based
      computational model of the spatio-temporal signalling processes within the
      follicle and (i) predict that FSH and LH form a gradient inside the follicle,
      (ii) show that the spatial distribution of FSH- and LH-receptors can arise from
      the well known regulatory interactions, and (iii) find that the differential
      activity of FSH and LH may well result from the distinct spatial localisation of
      their receptors, even when both receptors respond with the same intracellular
      signalling cascade to their ligand. CONCLUSION: The model integrates the large
      amount of published data into a consistent framework that can now be used to
      better understand how observed defects translate into failed follicle maturation.

PMID- 23856356
TI  - The presence, role and clinical use of spermatozoal RNAs.
AB  - BACKGROUND Spermatozoa are highly differentiated, transcriptionally inert cells
      characterized by a compact nucleus with minimal cytoplasm. Nevertheless they
      contain a suite of unique RNAs that are delivered to oocyte upon fertilization.
      They are likely integrated as part of many different processes including genome
      recognition, consolidation-confrontation, early embryonic development and
      epigenetic transgenerational inherence. Spermatozoal RNAs also provide a window
      into the developmental history of each sperm thereby providing biomarkers of
      fertility and pregnancy outcome which are being intensely studied. METHODS
      Literature searches were performed to review the majority of spermatozoal RNA
      studies that described potential functions and clinical applications with
      emphasis on Next-Generation Sequencing. Human, mouse, bovine and stallion were
      compared as their distribution and composition of spermatozoal RNAs, using these
      techniques, have been described. RESULTS Comparisons highlighted the complexity
      of the population of spermatozoal RNAs that comprises rRNA, mRNA and both large
      and small non-coding RNAs. RNA-seq analysis has revealed that only a fraction of
      the larger RNAs retain their structure. While rRNAs are the most abundant and are
      highly fragmented, ensuring a translationally quiescent state, other RNAs
      including some mRNAs retain their functional potential, thereby increasing the
      opportunity for regulatory interactions. Abundant small non-coding RNAs retained
      in spermatozoa include miRNAs and piRNAs. Some, like miR-34c are essential to the
      early embryo development required for the first cellular division. Others like
      the piRNAs are likely part of the genomic dance of confrontation and
      consolidation. Other non-coding spermatozoal RNAs include transposable elements,
      annotated lnc-RNAs, intronic retained elements, exonic elements, chromatin
      associated RNAs, small-nuclear ILF3/NF30 associated RNAs, quiescent RNAs, mse
      tRNAs and YRNAs. Some non-coding RNAs are known to act as epigenetic modifiers,
      inducing histone modifications and DNA methylation, perhaps playing a role in
      transgenerational epigenetic inherence. Transcript profiling holds considerable
      potential for the discovery of fertility biomarkers for both agriculture and
      human medicine. Comparing the differential RNA profiles of infertile and fertile
      individuals as well as assessing species similarities, should resolve the
      regulatory pathways contributing to male factor infertility. CONCLUSIONS Dad
      delivers a complex population of RNAs to the oocyte at fertilization that likely
      influences fertilization, embryo development, the phenotype of the offspring and
      possibly future generations. Development is continuing on the use of spermatozoal
      RNA profiles as phenotypic markers of male factor status for use as clinical
      diagnostics of the father's contribution to the birth of a healthy child. 

PMID- 23856360
TI  - Factors that predict 1-month mortality in patients with pregnancy-specific liver
      disease.
AB  - BACKGROUND & AIMS: Pregnancy-specific liver diseases such as acute fatty liver of
      pregnancy; hemolysis, elevated liver enzymes and low platelet syndrome; and
      preeclampsia-associated liver disease are associated with considerable morbidity
      and mortality. We investigated the ability of the model for end-stage liver
      disease (MELD) to predict 1-month mortality among patients with pregnancy
      specific liver diseases. We also developed and tested a model to predict
      mortality based on features of pregnancy-specific liver diseases. METHODS: We
      performed a retrospective study, analyzing hospital admission, clinical,
      hematologic, and biochemical data collected from 130 patients with pregnancy
      specific liver diseases admitted to the St. John's Medical College Hospital
      (Bangalore, India) from January 2000 through April 2011. Patients were followed
      up until 3 months after delivery or death. Logistic regression models were fitted
      using the MELD score and other variables identified as clinically or
      statistically significant. The predictive accuracy and calibration of the models
      were assessed by receiver operating characteristic curves and the Hosmer-Lemeshow
      goodness-of-fit test. RESULTS: Thirty-two patients (24.6%) died. Mortalities from
      pregnancy-specific liver diseases within 1 month of admission among patients with
      MELD scores of 20 to 29, 30 to 39, or 40 or greater were 24.2%, 45.45%, and
      90.9%, respectively. Univariate analysis identified encephalopathy, ascites,
      serum total protein, bilirubin, platelet count, alkaline phosphatase, serum
      creatinine, and international normalized ratio (INR) as significant variables.
      Multivariate analysis identified total bilirubin (P < .001) and INR (P < .003) as
      significant predictors of mortality. MELD score and a model based on only 2
      variables (bilirubin level and INR) accurately predicted mortality (C statistics,
      0.83 and 0.86, respectively) and were well calibrated (Hosmer-Lemeshow chi(2) =
      9.7 [P = .28] and 1.9 [P = .98], respectively). CONCLUSIONS: A new logistic model
      based on only 2 variables (INR and total bilirubin) was comparable with the MELD
      model in predicting mortality among women with pregnancy-specific liver diseases.

PMID- 23856361
TI  - Adalimumab induces deep remission in patients with Crohn's disease.
AB  - BACKGROUND & AIMS: Patients with moderate to severe ileocolonic Crohn's disease
      (CD) who received adalimumab induction and maintenance therapy had greater rates
      of mucosal healing than patients who received placebo after adalimumab induction
      therapy in a 52-week trial (EXTend the Safety and Efficacy of Adalimumab Through
      ENDoscopic Healing). We investigated whether this treatment also induced deep
      remission-a composite clinical and endoscopic end point. METHODS: Rates of deep
      remission, defined as the absence of mucosal ulceration and CD Activity Index
      scores less than 150, were compared between patients given continuous adalimumab
      and those given only induction therapy followed by placebo. We assessed the
      relationships between deep remission and other outcomes among patients who
      received adalimumab. The outcomes of patients with deep remission were compared
      with those of patients with only the absence of mucosal ulceration or only
      clinical remission. RESULTS: Rates of deep remission were 16% in patients given
      adalimumab vs 10% in those given placebo (P = .34) at week 12, and 19% vs 0% (P <
      .001) at week 52. Rates of deep remission were greatest among patients who
      received adalimumab and had CD for 2 years or less (33% at weeks 12 and 52). At
      week 52, patients who achieved deep remission at week 12 required significantly
      fewer adalimumab treatment adjustments, hospitalizations, and CD-related
      surgeries; had significantly less activity impairment; and had better quality of
      life and physical function compared with patients not achieving deep remission.
      Deep remission generally was associated with better outcomes than only an absence
      of mucosal ulceration; outcomes of patients with deep remission vs only clinical
      remission were similar. Deep remission was associated with estimated total cost
      savings of $10,360 (from weeks 12 through 52) compared with lack of deep
      remission. CONCLUSIONS: In an exploratory study of patients with moderate to
      severe ileocolonic CD who received adalimumab induction and maintenance therapy,
      patients achieving deep remission appeared to have better 1-year outcomes than
      those not achieving deep remission. These findings should be validated in large,
      prospective trials. ClinicalTrials.gov number: NCT00348283.

PMID- 23856363
TI  - Clinical features and outcomes of foot keloids treated using complete surgical
      excision and full thickness skin grafting followed by corticosteroid injections.
AB  - BACKGROUND: Keloids are often resistant to treatment and have high recurrence
      rates. To the best of the authors' knowledge, however, there have been very few
      case reports related to foot keloids. The purpose of this retrospective case
      series was to summarize the baseline characteristics of a cohort of patients,
      introduce our treatment regimen for the successful treatment of foot keloids.
      METHODS: Patients were treated with surgical excision followed by full thickness
      skin grafting combined with postoperative steroid injections combined with
      silicone gel sheeting over a period of eight years from December 2004 to November
      2012 at our institution. Subjective outcome was evaluated using Patient Scar
      Assessment Scales. The final objective outcome was judged by two independent
      physicians at the time of 12 months after treatment as recurrence or non
      recurrence. RESULTS: Of 79 patients, 75 (94.9%) were women and 4 (5.1%) were men.
      The average age was 18 (range 7-43) years. The average pretreatment total size of
      the lesions was 50 (range 18-150) cm. The number of patients treated for a
      primary foot keloid was 29 (36.7%), and 70 patients (63.3%) were treated for a
      recurrent keloid that failed to respond to prior treatments. Prior treatments
      included single therapies such as surgical excision alone (4 patients, 5.1%),
      prior steroid injection alone (33 patients, 41.8%), and laser therapy (2
      patients, 2.5%). Other therapies included combination treatments (11 patients,
      13.9%). Most patients reported improved Patient Scar Assessment Scale by lapse of
      time. All patients completed the treatment regimen and follow-up of 12 months. Of
      these patients, 62 patients (78.5%) achieved successful treatment, while the
      remaining 17 (21.5%) experienced recurrence. CONCLUSIONS: We successfully treated
      foot keloids using complete surgical excision and full thickness skin grafting
      followed by four corticosteroid injections (at one month intervals).

PMID- 23856364
TI  - Major infection events over 5 years: how is media coverage influencing online
      information needs of health care professionals and the public?
AB  - BACKGROUND: The last decade witnessed turbulent events in public health. Emerging
      infections, increase of antimicrobial resistance, deliberately released threats
      and ongoing battles with common illnesses were amplified by the spread of disease
      through increased international travel. The Internet has dramatically changed the
      availability of information about outbreaks; however, little research has been
      done in comparing the online behavior of public and professionals around the same
      events and the effect of media coverage of outbreaks on information needs.
      OBJECTIVE: To investigate professional and public online information needs around
      major infection outbreaks and correlate these with media coverage. Questions
      include (1) How do health care professionals' online needs for public health and
      infection control information differ from those of the public?, (2) Does dramatic
      media coverage of outbreaks contribute to the information needs among the
      public?, and (3) How do incidents of diseases and major policy events relate to
      the information needs of professionals? METHODS: We used three longitudinal time
      based datasets from mid-2006 until end of 2010: (1) a unique record of
      professional online behavior on UK infection portals: National electronic Library
      of Infection and National Resource of Infection Control (NeLI/NRIC), (2)
      equivalent public online information needs (Google Trends), and (3) relevant
      media coverage (LexisNexis). Analysis of NeLI/NRIC logs identified the highest
      interest around six major infectious diseases: Clostridium difficile (C
      difficile)/Methicillin-resistant Staphylococcus aureus (MRSA), tuberculosis,
      meningitis, norovirus, and influenza. After pre-processing, the datasets were
      analyzed and triangulated with each other. RESULTS: Public information needs were
      more static, following the actual disease occurrence less than those of
      professionals, whose needs increase with public health events (eg, MRSA/C
      difficile) and the release of major national policies or important documents.
      Media coverage of events resulted in major public interest (eg, the 2007/2008 UK
      outbreak of C difficile/MRSA). An exception was norovirus, showing a seasonal
      pattern for both public and professionals, which matched the periodic disease
      occurrence. Meningitis was a clear example of a disease with heightened media
      coverage tending to focus on individual and celebrity cases. Influenza was a
      major concern during the 2009 H1N1 outbreak creating massive public interest in
      line with the spring and autumn peaks in cases; although in autumn 2009, there
      was no corresponding increase in media coverage. Online resources play an
      increasing role in fulfilling professionals' and public information needs.
      CONCLUSIONS: Significant factors related to a surge of professional interest
      around a disease were typically key publications and major policy changes. Public
      interests seem more static and correlate with media influence but to a lesser
      extent than expected. The only exception was norovirus, exhibiting online public
      and professional interest correlating with seasonal occurrences of the disease.
      Public health agencies with responsibility for risk communication of public
      health events, in particular during outbreaks and emergencies, need to
      collaborate with media in order to ensure the coverage is high quality and
      evidence-based, while professionals' information needs remain mainly fulfilled by
      online open access to key resources.

PMID- 23856365
TI  - Prognostic value of neutrophil to lymphocyte ratio in patients with acute
      pulmonary embolism: a restrospective study.
AB  - BACKGROUND: Acute pulmonary embolism (PE) is a serious clinical condition
      characterised by a high mortality rate. Previous studies showed that leukocytosis
      was associated with recurrences of venous thromboemboli, major bleeding and
      increased mortality. The aim of the present study was to investigate the
      prognostic value of neutrophil to lymphocyte ratio (NLR) in patients with acute
      PE during short term follow-up. METHOD: A total of 640 patients were screened by
      I26 code of ICD-9 and 359 patients were included as cases of confirmed acute PE.
      Admission blood counts and clinical data were obtained from medical charts. The
      predictors of 30-day mortality were examined. RESULTS: Fifty-one out of 359
      patients (14.2%) included in the study died during 30 days follow-up. In
      multivariate Cox regression analysis systolic blood pressure (HR:0.97 (0.94-0.99
      CI95%), p=0.019), diabetes mellitus (HR:3.3 (1.30-8.39 CI95%), p=0.012), CK
      MB(HR:1.03 (1.01-1.06 CI95%), p=0.024) and NLR (HR:1.03 (1.01-1.06 CI95%),
      p=0.008) were predictors of 30-day mortality. An optimal cut-off value of NLR was
      determined as 9.2 by using ROC curve. Hazards ratio of NLR>9.2 was found to be
      3.60 (1.44-9.18 CI95%, p=0.006). NLR>9.2 had a sensitivity, specificity, negative
      predictive value, and positive predictive value of 68.6%, 80.5%, 93.9% and 36.5%,
      respectively. CONCLUSION: NLR on hospital admission may be a predictor of 30-day
      mortality in acute PE. Since complete blood count is a part of the routine
      laboratory investigation in the most hospitalised patients use and preliminary
      promising results of this study, NLR should be investigated in future prospective
      randomised trials regarding prognostic value in acute PE.

PMID- 23856366
TI  - Heart research advances using database search engines, Human Protein Atlas and
      the Sydney Heart Bank.
AB  - This Methodological Review is intended as a guide for research students who may
      have just discovered a human "novel" cardiac protein, but it may also help hard
      pressed reviewers of journal submissions on a "novel" protein reported in an
      animal model of human heart failure. Whether you are an expert or not, you may
      know little or nothing about this particular protein of interest. In this review
      we provide a strategic guide on how to proceed. We ask: How do you discover what
      has been published (even in an abstract or research report) about this protein?
      Everyone knows how to undertake literature searches using PubMed and Medline but
      these are usually encyclopaedic, often producing long lists of papers, most of
      which are either irrelevant or only vaguely relevant to your query. Relatively
      few will be aware of more advanced search engines such as Google Scholar and even
      fewer will know about Quertle. Next, we provide a strategy for discovering if
      your "novel" protein is expressed in the normal, healthy human heart, and if it
      is, we show you how to investigate its subcellular location. This can usually be
      achieved by visiting the website "Human Protein Atlas" without doing a single
      experiment. Finally, we provide a pathway to discovering if your protein of
      interest changes its expression level with heart failure/disease or with ageing. 

PMID- 23856367
TI  - Effect of endocannabinoids on soybean lipoxygenase-1 activity.
AB  - Endocannabinoids appear to be involved in a variety of physiological processes.
      Lipoxygenase activity has been known to be affected by unsaturated fatty acids or
      phenolic compounds. In this study, we examined whether endocannabinoids
      containing both N-acyl group and phenolic group can affect the activity of
      soybean lipoxygenase (LOX)-1, similar to mammalian 15-lipoxygenase in
      physicochemical properties. First, N-arachidonoyl dopamine and N-oleoyl dopamine
      were found to inhibit soybean LOX-1-catalyzed oxygenation of linoleic acid in a
      non-competitive manner with a Ki value of 3.7 MUM and 6.2 MUM, respectively.
      Meanwhile, other endocannabinoids failed to show a remarkable inhibition of
      soybean LOX-1. Separately, N-arachidonoyl dopamine and N-arachidonoyl serotonin
      were observed to inactivate soybean LOX-1 with Kin value of 27 MUM and 24 MUM,
      respectively, and k3 value of 0.12 min(-1) and 0.35 min(-1), respectively.
      Furthermore, such an inactivation was enhanced by ascorbic acid, but suppressed
      by 13(S)-hydroperoxy-9,11-octadecadienoic acid. Taken together, it is proposed
      that endocannabinoids containing polyunsaturated acyl moiety and phenolic group
      may be efficient for the inhibition as well as inactivation of 15-lipoxygenase.

PMID- 23856368
TI  - Bringing global health to center stage: the launch of a new journal.

PMID- 23856369
TI  - New Joint Centre for Infectious Diseases Research underpins world leading
      research efforts to develop new tools and technologies to assist in national and
      international disease control efforts.

PMID- 23856370
TI  - Climate change impacts on water salinity and health.
AB  - It is estimated that 884 million people do not have access to clean drinking
      water in the world. Increasing salinity of natural drinking water sources has
      been reported as one of the many problems that affect low-income countries, but
      one which has not been fully explored. This problem is exacerbated by rising sea
      levels, owing to climate change, and other contributing factors, like changes in
      fresh water flow from rivers and increased shrimp farming along the coastal
      areas. In some countries, desalination plants are used to partly remove salt and
      other minerals from water sources, but this is unlikely to be a sustainable
      option for low-income countries affected by high salinity. Using the example of
      Bangladesh as a model country, the following research indicates that the problem
      of salinity can have serious implications with regard to rising rates of
      hypertension and other public health problems among large sectors of the
      worldwide population. 

PMID- 23856371
TI  - Health advocacy with Gapminder animated statistics.

PMID- 23856372
TI  - The fog of war: why the environmental crusade for anadromous fish species in
      California could disarm the state's local vector control districts in their war
      against mosquitoes.
AB  - In California, local mosquito and vector control districts have successfully
      controlled mosquito and vector-borne diseases by improving drainage patterns and
      applying pesticides. The Bay-Delta Conservation Plan, which is a proposed habitat
      conservation plan for the Sacramento-San Joaquin Bay-Delta estuary, proposes to
      add over 70,000 acres of habitat in the Delta to improve conditions for
      threatened and endangered aquatic and terrestrial species. This habitat could
      also be a suitable mosquito breeding habitat, which will be located in close
      proximity to urban and suburban communities. Wetland management practices and
      continued pesticide applications in the Delta could mitigate the effects of a new
      mosquito breeding habitat. Recent legal developments, however, require districts
      to obtain and comply with Clean Water Act permits, which restrict the application
      of pesticides in or near waters of the United States. Moreover, the U.S.
      Environmental Protection Agency has taken the first step in a rulemaking process
      that could further limit or prohibit the use of certain vector control pesticides
      in the Delta. In the near term and until less harmful methods for mosquito
      control are available, local vector control districts' application of mosquito
      control pesticides should be exempt from Clean Water Act permit requirements.

PMID- 23856373
TI  - Redefining syndromic surveillance.
AB  - With growing concerns about international spread of disease and expanding use of
      early disease detection surveillance methods, the field of syndromic surveillance
      has received increased attention over the last decade. The purpose of this
      article is to clarify the various meanings that have been assigned to the term
      syndromic surveillance and to propose a refined categorization of the
      characteristics of these systems. Existing literature and conference proceedings
      were examined on syndromic surveillance from 1998 to 2010, focusing on low- and
      middle-income settings. Based on the 36 unique definitions of syndromic
      surveillance found in the literature, five commonly accepted principles of
      syndromic surveillance systems were identified, as well as two fundamental
      categories: specific and non-specific disease detection. Ultimately, the proposed
      categorization of syndromic surveillance distinguishes between systems that focus
      on detecting defined syndromes or outcomes of interest and those that aim to
      uncover non-specific trends that suggest an outbreak may be occurring. By
      providing an accurate and comprehensive picture of this field's capabilities, and
      differentiating among system types, a unified understanding of the syndromic
      surveillance field can be developed, encouraging the adoption, investment in, and
      implementation of these systems in settings that need bolstered surveillance
      capacity, particularly low- and middle-income countries. 

PMID- 23856374
TI  - Could influenza transmission be reduced by restricting mass gatherings? Towards
      an evidence-based policy framework.
AB  - INTRODUCTION: Mass gatherings (MG) may provide ideal conditions for influenza
      transmission. The evidence for an association between MG and influenza
      transmission is reviewed to assess whether restricting MG may reduce
      transmission. METHODS: Major databases were searched (Pubmed, EMBASE, Scopus,
      CINAHL), producing 1706 articles that were sifted by title, abstract, and full
      text. A narrative approach was adopted for data synthesis. RESULTS: Twenty-four
      papers met the inclusion criteria, covering MG of varying sizes and settings, and
      including 9 observational studies, 10 outbreak reports, 4 event reports, and a
      quasi-experimental study. There is some evidence that certain types of MG may be
      associated with increased risk of influenza transmission. MG may also "seed" new
      strains into an area, and may instigate community transmission in a pandemic.
      Restricting MGs, in combination with other social distancing interventions, may
      help reduce transmission, but it was not possible to identify conclusive evidence
      on the individual effect of MG restriction alone. Evidence suggests that event
      duration and crowdedness may be the key factors that determine the risk of
      influenza transmission, and possibly the type of venue (indoor/outdoor).
      CONCLUSION: These factors potentially represent a basis for a policy-making
      framework for MG restrictions in the event of a severe pandemic.

PMID- 23856375
TI  - Marked regional variations in the prevalence of sickle cell disease and beta
      thalassemia in Saudi Arabia: findings from the premarital screening and genetic
      counseling program.
AB  - BACKGROUND: Hemoglobinopathies represent a major public health problem in Saudi
      Arabia (SA). Reports suggest that their higher prevalence is not evenly
      distributed in SA. Regional differences were studied in sickle cell disease and
      beta-thalassemia and their at-risk marriages using national data. METHODS: The
      carrier and case status of sickle cell disease and beta-thalassemia were
      determined in couples approaching marriage between 2004 and 2009 using standard
      blood tests. Prevalence of both diseases and at-risk marriages in different SA
      administrative and geographical regions were calculated and compared. RESULTS: A
      total of 15,72,140 men and women were examined over 6 years. This represented
      0.06% of the entire population of Saudi Arabia. The prevalence of couples who
      tested positive for sickle cell was 45.1 (42.4 for carriers and 2.7 for cases)
      per 1000 persons examined. The prevalence was highest in the Eastern region
      (134.1 per 1000), followed by Southern and Western regions (55.6 and 28.5 per
      1000, respectively) and lowest in Central and Northern regions (13.7 and 13.5 per
      1000, respectively). The prevalence of couples testing positive for beta
      thalassemia was 18.5 (18.0 for carriers and 0.5 for cases) per 1000 persons
      examined. The prevalence was highest in the Eastern region (59.0), moderate in
      the Southern, Western and Central regions (14.2, 10.2, and 10.1 per 1000,
      respectively) and lowest in the Northern region (3.9). CONCLUSION: Vast regional
      differences in hemoglobinopathies among adult Saudis are being reported that may
      help policy makers better allocate resources of available preventive programs.

PMID- 23856376
TI  - In the beginning there were soft collagen-cell gels: towards better 3D connective
      tissue models?
AB  - In the 40 years since Elsdale and Bard's analysis of fibroblast culture in
      collagen gels we have moved far beyond the concept that such 3D fibril network
      systems are better models than monolayer cultures. This review analyses key
      aspects of that progression of models, against a background of what exactly each
      model system tries to mimic. This story tracks our increasing understanding of
      fibroblast responses to soft collagen gels, in particularly their cytoskeletal
      contraction, migration and integrin attachment. The focus on fibroblast mechano
      function has generated models designed to directly measure the overall force
      generated by fibroblast populations, their reaction to external loads and the
      role of the matrix structure. Key steps along this evolution of 3D collagen
      models have been designed to mimic normal skin, wound repair, tissue
      morphogenesis and remodelling, growth and contracture during scarring/fibrosis.
      As new models are developed to understand cell-mechanical function in connective
      tissues the collagen material has become progressively more important, now being
      engineered to mimic more complex aspects of native extracellular matrix
      structure. These have included collagen fibril density, alignment and
      hierarchical structure, controlling material stiffness and anisotropy. But of
      these, tissue-like collagen density is key in that it contributes to control of
      the others. It is concluded that across this 40 year window major progress has
      been made towards establishing a family of 3D experimental collagen tissue
      models, suitable to investigate normal and pathological fibroblast mechano
      functions.

PMID- 23856378
TI  - Compound heterozygosity for dominant and recessive GJB2 mutations in a Tunisian
      family and association with successful cochlear implant outcome.
AB  - OBJECTIVES: Mutations of GJB2 encoding connexin 26 are the most common cause of
      hearing loss. They are responsible for up to 50% of ARNSHL. The pathogenic
      mutations in this gene are generally inherited recessively. Dominant mutations in
      GJB2 also cause hearing loss, either in isolated non-syndromic form or as part of
      a syndrome associated with various skin disorders. METHODS: We screened a
      Tunisian child affected by congenital, bilateral, profound, sensorineural hearing
      loss for mutations in GJB2 gene using PCR and direct sequencing. RESULTS: The
      proband was found to be compound heterozygous for recessive and dominant GJB2
      mutations respectively p.V37I (c.109G > A) and p.R143Q (c.428G > A). Surprisingly
      the hearing mother is a carrier for this dominant GJB2 mutation. This proband
      underwent a cochlear implant at four years old. The evaluation using APCEI and IT
      MAIS tests at six months post implantation indicates a successful cochlear
      implant outcome since the deaf child began to acquire language abilities and
      auditory sensation. CONCLUSIONS: The p.R143Q mutation was described for the first
      time in Tunisia. We confirm the low penetrance of this mutation since the proband
      mother is a carrier despite her normal hearing. We show the effectiveness of
      cochlear implant to restore the communication abilities and auditory sensation
      for our patient.

PMID- 23856377
TI  - Antioxidant therapeutics: Pandora's box.
AB  - Evolution has favored the utilization of dioxygen (O2) in the development of
      complex multicellular organisms. O2 is actually a toxic mutagenic gas that is
      highly oxidizing and combustible. It is thought that plants are largely to blame
      for polluting the earth's atmosphere with O2 owing to the development of
      photosynthesis by blue-green algae over 2 billion years ago. The rise of the
      plants and atmospheric O2 levels placed evolutionary stress on organisms to adapt
      or become extinct. This implies that all the surviving creatures on our planet
      are mutants that have adapted to the "abnormal biology" of O2. Much of the
      adaptation to the presence of O2 in biological systems comes from well
      coordinated antioxidant and repair systems that focus on converting O2 to its
      most reduced form, water (H2O), and the repair and replacement of damaged
      cellular macromolecules. Biological systems have also harnessed O2's reactive
      properties for energy production, xenobiotic metabolism, and host defense and as
      a signaling messenger and redox modulator of a number of cell signaling pathways.
      Many of these systems involve electron transport systems and offer many different
      mechanisms by which antioxidant therapeutics can alternatively produce an
      antioxidant effect without directly scavenging oxygen-derived reactive species.
      It is likely that each agent will have a different set of mechanisms that may
      change depending on the model of oxidative stress, organ system, or disease
      state. An important point is that all biological processes of aerobes have
      coevolved with O2 and this creates a Pandora's box for trying to understand the
      mechanism(s) of action of antioxidants being developed as therapeutic agents. 

PMID- 23856379
TI  - A novel frameshift mutation (c.405delC) in the GJB2 gene associated with
      autosomal recessive hearing loss in two Tunisian families.
AB  - OBJECTIVES: Mutations in GJB2 are found to be responsible for 50% of congenital
      autosomal recessive non-syndromic hearing loss, one of the most important
      mutations in this gene is the c.35delG, which is responsible for the majority of
      GJB2 related deafness in the Tunisian population. The aim of this study was to
      determine the molecular etiology of hearing loss in two Tunisian individuals.
      METHODS: We screened two Tunisian individuals affected by congenital, bilateral,
      profound, sensorineural hearing loss for mutations in GJB2 gene using PCR and
      direct sequencing. RESULTS: We identified a novel frameshift mutation in the GJB2
      gene, the c.405delC resulting in a truncated protein (p.Tyr136Thrfs*32). It was
      found in compound heterozygosity with the c.35delG in two non-consanguineous
      unrelated families from Tunisia. One patient underwent a cochlear implant at 4
      years. Initial evaluations post-implantation indicate a successful cochlear
      implant outcome since the patient began to acquire language abilities and
      auditory sensation. CONCLUSIONS: With this novel GJB2 mutation, the mutational
      spectrum of this gene continues to broaden in our population. The occurrence of
      biallelic GJB2 mutations for the other deaf girl, despite the neonatal pain and
      hypotension due to complicated delivery, led us to confirm the importance of GJB2
      screening for cochlear implant candidates regardless of the etiology of deafness
      in populations with a relatively high frequency of GJB2 mutation carriers.

PMID- 23856380
TI  - Association of a change in erythropoiesis-stimulating agent dose during
      hospitalization and subsequent hemoglobin levels and transfusions in hemodialysis
      patients.
AB  - BACKGROUND: Erythropoiesis-stimulating agent (ESA) doses are often increased in
      hospitalized dialysis patients in response to acute anemia with unknown
      consequences. We sought to determine whether increases in ESA dose during
      hospital admission were associated with changes in transfusion requirement and
      risk of exceeding recommended hemoglobin targets. STUDY DESIGN: Retrospective
      cohort study. SETTING & PARTICIPANTS: Linked administrative, laboratory, and
      blood transfusion data were used to identify a total of 700 hospitalizations
      involving 484 long-term hemodialysis patients between 2004 and 2008 in the
      Calgary Health Region, Canada. PREDICTOR: Change in ESA dose was determined by
      comparing the average weekly dose over the 6 weeks preceding admission to that
      administered during the 14 days following admission. OUTCOMES & MEASUREMENTS: Cox
      proportional hazards models adjusted for baseline patient characteristics were
      used to model the association between changes in ESA dose and outcomes, including
      exceeding recommended hemoglobin targets, receipt of blood transfusion,
      cardiovascular outcomes, and death. RESULTS: There was a significant increase in
      the risk of exceeding recommended hemoglobin targets as the ESA dose was
      increased by >=40 MUg/wk (equivalent darbepoetin alfa dose) above baseline (HR,
      2.21; 95% CI, 1.19-4.10). However, an increase in ESA dose was not associated
      with reduced need for blood transfusion, risk of cardiovascular outcomes, or
      death. LIMITATIONS: Residual confounding by clinical events that may lead to
      changes in the management of patients and may have influenced the observed
      relationship between predictor and outcomes. CONCLUSIONS: Increasing the ESA dose
      at hospitalization in hemodialysis patients is associated with higher risk of
      exceeding recommended hemoglobin targets, but does not appear to be associated
      with the need for transfusion, risk of cardiovascular outcomes, or death.

PMID- 23856381
TI  - Up-and-down designs for phase I clinical trials.
AB  - Various up-and-down designs have been proposed to improve the operating
      characteristics of the traditional "3 + 3" design, but they have been of limited
      use in practice. A major impediment to the adoption of the improved up-and-down
      designs is a lack of general guidance and a comprehensive assessment of the
      operating characteristics of these designs under practical clinical settings. To
      fill this gap, we review six up-and-down designs: the "3 + 3" design, accelerated
      titration design, biased coin design, k-in-a-row design, group up-and-down design
      and cumulative group up-and-down design. We conduct comprehensive simulation
      studies to evaluate their operating characteristics under various practical
      settings, and compare their performance to a theoretical optimal bound of
      nonparametric designs. The results show that the cumulative group up-and-down
      design has the best overall performance in terms of selecting the maximum
      tolerated dose (MTD), assigning patients to the MTD and patient safety. Its
      performance is generally close to the upper bound of nonparametric designs, but
      improvement seems possible in some cases.

PMID- 23856382
TI  - Assessing the effects of different pectins addition on color quality and
      antioxidant properties of blackberry jam.
AB  - BACKGROUND: In the last years pectin and other hydrocolloids were tested for
      improving the color stability and the retention of bioactive compounds in gelled
      fruit-based products. In line with these concerns, our study has been directed to
      quantify the changes in antioxidant status and color indices of blackberry jam
      obtained with different types of pectin (degree of esterification: DE, degree of
      amidation: DA) and doses in response to processing and storage for 1, 3 and 6
      months at 20 degrees C. RESULTS: Blackberry jam was obtained by a traditional
      procedure used in households or small-scale systems with different commercial
      pectins (HMP: high-methoxyl pectin, LMP: low-methoxyl pectin and LMAP: low
      methoxyl amidated pectin) added to three concentrations (0.3, 0.7 and 1.0%) and
      investigated in terms of total monomeric anthocyanins (TMA), antioxidant capacity
      expressed as ferric reducing antioxidant power (FRAP), total phenolics (TP),
      color density (CD) and percent of polymeric color, PC (%). Thermal processing
      resulted in significant depreciation of analyzed parameters reported to the
      corresponding values of fresh fruit as follows: TMA (69-82%), TP (33-55%) and
      FRAP (18-52%). Biologically active compounds and color were best retained one day
      post-processing in jams with LMAP followed by samples with LMP and HMP. Storage
      for 6 months brings along additional dramatic losses reported to the values
      recorded one day post-processing as follows: TMA (31-56%), TP (29-51%) and FRAP
      (20-41%). Also, both processing and storage resulted in significant increases in
      PC (%). The pectin type and dosage are very influential factors for limiting the
      alterations occurring in response to processing and storage. The best color
      retention and the highest TMA, TP and FRAP were achieved by LMAP, followed by LMP
      and HMP. Additionally, a high level of bioactive compounds in jam could be
      related to a high dose of pectin. LMAP to a level of 1% is the most indicated to
      provide the highest antioxidant properties in jam. CONCLUSIONS: The retention of
      bioactive compounds and jam color stability were strongly dependent on the pectin
      type and dosage. By a proper selection of pectin type and dose could be limited
      the losses recorded in response to processing and storage.

PMID- 23856383
TI  - [Gonococcal vulvovaginitis in prepubertal girls: sexual abuse or accidental
      transmission?].

PMID- 23856384
TI  - A study of the virulence in mice of high copying fidelity variants of human
      enterovirus 71.
AB  - Polioviruses with a G64S mutation in the 3D polymerase have enhanced replication
      fidelity and are attenuated in animal models. Here we describe the mouse
      virulence properties of high replication fidelity 3D polymerase variants of human
      enterovirus 71 (HEV71), with mutations at positions 3D-S264L, 3D-G64R or at 3D
      S264L plus 3D-G64R. Mouse-adapted strains (MP-G64R, MP-S264L and MP-S264L-G64R)
      were constructed in order to compare the virulence of the 3D polymerase variants
      with that of mouse-adapted parental virus (MP-26M). MP-S264L and MP-S264L-G64R
      were attenuated in mice (mean survival time 7.0 and 7.5 days p.i., respectively)
      compared to MP-G64R and MP-26M (mean survival time 6.5 and 6.0 days p.i.,
      respectively). MP-26M and MP-G64R infection induced early onset, severe
      generalised necrotising myositis, whereas MP-S264L and MP-S264L-G64R infection
      induced a later onset, mild and focal skeletal muscle myositis. Our findings
      demonstrate that only the 3D-S264L mutation attenuates HEV71 in mice, suggesting
      that the high replication fidelity phenotype is not essential for virulence
      attenuation in this model.

PMID- 23856385
TI  - Medroxyprogesterone acetate-driven increase in breast cancer risk might be
      mediated via cross-talk with growth factors in the presence of progesterone
      receptor membrane component-1.
AB  - BACKGROUND: The WHI trial suggests an increase of breast cancer in postmenopausal
      women probably according to the progestogenic compound, i.e. medroxyprogesterone
      acetate (MPA). However, the mechanism for a possible carcinogenic effect of MPA
      remains unclear so far. Progesterone receptor membrane component-1 (PGRMC1) may
      be important in tumorigenesis and thus may increase breast cancer risk. We
      investigated the influence of MPA alone and in combination with growth factors on
      breast cancer cells overexpressing PGRMC1. METHODS: MCF-7 cells were stably
      transfected with PGRMC1 expression plasmid (WT-12 cells). Cells transfected only
      with the vector were used as control cells (EVC-cells). Medroxyprogesterone
      acetate (MPA), norethisterone (NET) and progesterone (P) were tested alone and in
      combination with a mixture of growth factors. Cell proliferation was measured by
      MTT assay. RESULTS: The growth factor mixture (GF) was able to induce cell
      proliferation in both cell types, however, the effect was much higher in the WT
      12 cells. In WT-12 cells both MPA and NET alone significantly increased cell
      proliferation with values of 40% and 97%, respectively. Progesterone, however,
      had no effect. In combination with GF MPA significantly further enhanced cell
      proliferation as compared to the effect of MPA alone and GF alone in both cell
      lines. NET showed no further increase as compared to NET alone and P had no
      effect. CONCLUSIONS: We could demonstrate a significant proliferative effect of
      MPA when combined with high concentrations of growth factors. This effect was
      more pronounced in breast cancer cells overexpressing PGRMC1. These results may
      be of clinical relevance since in the combined WHI trial an increased breast
      cancer risk was found during treatment with conjugated equine estrogens plus MPA.

PMID- 23856386
TI  - The bioluminescent Listeria monocytogenes strain Xen32 is defective in flagella
      expression and highly attenuated in orally infected BALB/cJ mice.
AB  - BACKGROUND: In vivo bioluminescence imaging (BLI) is a powerful method for the
      analysis of host-pathogen interactions in small animal models. The commercially
      available bioluminescent Listeria monocytogenes strain Xen32 is commonly used to
      analyse immune functions in knockout mice and pathomechanisms of listeriosis.
      FINDINGS: To analyse and image listerial dissemination after oral infection we
      have generated a murinised Xen32 strain (Xen32-mur) which expresses a previously
      described mouse-adapted internalin A. This strain was used alongside the Xen32
      wild type strain and the bioluminescent L. monocytogenes strains EGDe-lux and
      murinised EGDe-mur-lux to characterise bacterial dissemination in orally
      inoculated BALB/cJ mice. After four days of infection, Xen32 and Xen32-mur
      infected mice displayed consistently higher rates of bioluminescence compared to
      EGDe-lux and EGDe-mur-lux infected animals. However, surprisingly both Xen32
      strains showed attenuated virulence in orally infected BALB/c mice that
      correlated with lower bacterial burden in internal organs at day 5 post
      infection, smaller losses in body weights and increased survival compared to EGDe
      lux or EGDe-mur-lux inoculated animals. The Xen32 strain was made bioluminescent
      by integration of a lux-kan transposon cassette into the listerial flaA locus. We
      show here that this integration results in Xen32 in a flaA frameshift mutation
      which makes this strain flagella deficient. CONCLUSIONS: The bioluminescent L.
      monocytogenes strain Xen32 is deficient in flagella expression and highly
      attenuated in orally infected BALB/c mice. As this listerial strain has been used
      in many BLI studies of murine listeriosis, it is important that the scientific
      community is aware of its reduced virulence in vivo.

PMID- 23856387
TI  - Personality traits, interpersonal problems and therapeutic alliance in early
      schizophrenia spectrum disorders.
AB  - BACKGROUND: The quality of the therapeutic alliance is associated with engagement
      in- and thus important to the outcome of- treatment in schizophrenia. In non
      psychotic disorders, general personality traits and individual patterns of
      interpersonal problems have been linked to the formation and quality of the
      therapeutic alliance. The role of these factors in relation to therapeutic
      alliance has not previously been explored in schizophrenia spectrum disorders.
      AIM: To investigate associations between personality traits, interpersonal
      problems and the quality of the therapeutic alliance in early schizophrenia
      spectrum disorders. METHODS: Demographic and clinical characteristics including
      Positive and Negative Syndrome Scale (PANSS) scores were assessed in 42 patients.
      Personality traits and interpersonal problems were assessed with the NEO Five
      factor Inventory (NEO-FFI) and the circumplex model of the Inventory of
      Interpersonal Problems (IIP-64C). Therapeutic alliance was measured with the
      Working Alliance Inventory - short form (WAI-S). RESULTS: Patient WAI-S scores
      were predicted by IIP-64C Submissive/Hostile interpersonal problems, age and
      PANSS excitative symptoms. Therapist WAI-S scores were predicted by NEO-FFI
      Agreeableness and the PANSS insight item. CONCLUSION: Core traits of personality
      and dimensions of interpersonal problems are associated with both patients' and
      therapists' perceptions of the quality of the working alliance.

PMID- 23856388
TI  - Lorazepam-diazepam protocol for catatonia in schizophrenia: a 21-case analysis.
AB  - OBJECTIVES: Catatonia is a unique clinical phenomenon characterized by concurrent
      motor, emotional, vegetative and behavioral signs. Benzodiazepines (BZD) and
      electroconvulsive therapy (ECT) can rapidly relieve catatonic signs. The
      lorazepam-diazepam protocol presented here has been proven to relieve catatonia
      in schizophrenia within a day. METHODS: From July 2002 to August 2011,
      schizophrenic patients requiring psychiatric intervention for catatonia in
      Kaohsiung Chang Gung Memorial Hospital were studied by medical chart review. The
      study used the Bush-Francis Catatonia Rating Scale (BFCRS). Patients receiving
      the lorazepam-diazepam protocol were identified. RESULTS: The survey included 21
      patients (eight males and 13 females) with a mean age of 30.3 +/- 12.6 years.
      Mean duration of schizophrenia was 4.7 +/- 5.6 years. Thirteen (61.9%) patients
      responded within 2 h, 18 (85.7%) responded within one day, and all became
      catatonia-free within a week. Mean BFCRS score was 9.9 +/- 3.0 before treatment.
      Patients that responded with a single intramuscular lorazepam injection had mean
      BFCRS score of 8.9 +/- 2.8, significantly lower than the mean score (11.6 +/-
      2.5) of the rest of the patients (p = 0.034). CONCLUSIONS: The lorazepam-diazepam
      protocol can rapidly relieve retarded catatonia in schizophrenia. Most patients
      became catatonia-free within one day but some may require up to a week. ECT
      should be considered if the protocol fails.

PMID- 23856389
TI  - Gender differences in demographic and clinical features and prescribing patterns
      of psychotropic medications in patients with major depressive disorder in China.
AB  - PURPOSE: Little is known about gender differences associated with major
      depressive disorder (MDD) in China. This study examined gender differences
      associated with other demographic and clinical characteristics and psychotropic
      drug treatment in Chinese patients with MDD. METHODS: A total of 1178 patients
      with MDD from 13 psychiatric hospitals or psychiatric units of general hospitals
      in China nationwide were enrolled. Cross-sectional data including patients'
      demographic and clinical characteristics and prescriptions of psychotropic
      medications were recorded using a standardized protocol and data collection
      procedure. RESULTS: The sample consisted of 793 female and 385 male patients.
      Univariate analyses revealed that male patients were younger than female
      patients, had a younger age of onset of depression, had less lifetime depressive
      episodes and had more bipolar features (i.e. patients who screened positive for
      hypomanic symptoms on the 32-item Hypomania Checklist, but did not meet the
      diagnostic criteria for DSM-IV bipolar disorders as measured by the Mini
      International Neuropsychiatric Interview). Also, men were more likely to be
      employed than women and less likely to have depressive episodes following
      stressful life events. In multivariate analyses, being employed, having bipolar
      features and not having depressive episodes following stressful life events were
      independently associated with being a male patient with major depressive
      disorder. There was no difference in use of psychotropic medications by gender.
      CONCLUSIONS: Most gender differences in MDD patients in this study are not
      consistent with findings of Western studies suggesting that gender differences in
      MDD may be determined by both biological and sociocultural differences among
      ethnically different patient populations.

PMID- 23856390
TI  - Exploring whether genetic differences between siblings explain sibling
      differences in criminal justice outcomes.
AB  - Research has revealed that despite many similarities, siblings raised within the
      same household have also been found to be markedly different from one another.
      Behavioral differences between siblings have been primarily attributed to
      differential exposure to a wide variety of environmental influences. The
      potential role that between-sibling genetic differences play in the development
      of behavioral differences has been overlooked in the extant literature. The
      current study examines the association between differences in three dopaminergic
      polymorphisms (DAT1, DRD2, and DRD4) and differences in arrest, incarceration,
      and multiple arrests between siblings. Between-sibling difference scores were
      estimated for each examined polymorphism and each criminal justice outcome
      measure (along with all controls). Ordinary least squares (OLS) regression models
      were estimated to examine the potential association between genetic differences
      between siblings and differences in experiences within the criminal justice
      system. Models were estimated for the full sample and then for the same-sex male
      and female subsamples separately. The results provide preliminary evidence that
      between-sibling differences in some of the examined dopaminergic polymorphisms
      are associated with differences in contact with the criminal justice system.
      Findings are discussed in more detail and suggestions for future research are
      also provided. 

PMID- 23856392
TI  - Lentivirus infections in sheep and goats: how big is the burden?

PMID- 23856391
TI  - Neurodevelopmental outcomes at 5 years in children exposed prenatally to maternal
      dental amalgam: the Seychelles Child Development Nutrition Study.
AB  - Limited human data are available to assess the association between prenatal
      mercury vapor (Hg0)) exposure from maternal dental amalgam restorations and
      neurodevelopment of children. We evaluated the association between maternal
      dental amalgam status during gestation and children's neurodevelopmental outcomes
      at 5 years in the Seychelles Child Development Nutrition Study (SCDNS). Maternal
      amalgam status was determined prospectively in a longitudinal cohort study
      examining the associations of prenatal exposure to nutrients and methylmercury
      (MeHg) with neurodevelopment. A total of 236 mother-child pairs initially
      enrolled in the SCDNS in 2001 were eligible to participate. Maternal amalgam
      status was measured as number of amalgam surfaces (the primary metric) and number
      of occlusal points. The neurodevelopmental assessment battery was comprised of
      age-appropriate tests of cognitive, language, and perceptual functions, and
      scholastic achievement. Linear regression analysis controlled for MeHg exposure,
      maternal fatty acid status, and other covariates relevant to child development.
      Maternal amalgam status evaluation yielded an average of 7.0 surfaces (range 0
      28) and 11.0 occlusal points (range 0-40) during pregnancy. Neither the number of
      maternal amalgam surfaces nor occlusal points were associated with any outcome.
      Our findings do not provide evidence to support a relationship between prenatal
      exposure to Hg0 from maternal dental amalgam and neurodevelopmental outcomes in
      children at 5 years of age.

PMID- 23856393
TI  - Can pervasive sensing address current challenges in global healthcare?
AB  - Important challenges facing global healthcare include the increase in the number
      of people affected by escalating healthcare costs, chronic and infectious
      diseases, the need for better and more affordable elderly care and expanding
      urbanisation combined with air and water pollution. Recent advances in pervasive
      sensing technologies have led to miniaturised sensor networks that can be worn or
      integrated within the living environment without affecting a person's daily
      patterns. These sensors promise to change healthcare from snapshot measurements
      of physiological parameters to continuous monitoring enabling clinicians to
      provide guidance on a daily basis. This article surveys several of the solutions
      provided by these sensor platforms from elderly care to neonatal monitoring and
      environmental mapping. Some of the opportunities available and the challenges
      facing the adoption of such technologies in large-scale epidemiological studies
      are also discussed. 

PMID- 23856394
TI  - The social context of tobacco products use among adolescents in Lebanon (MedSPAD
      Lebanon).
AB  - BACKGROUND: Current data from the Middle East suggest a rapid increase in the
      incidence of smoking water-pipes (narguileh in Lebanon) in parallel with
      cigarettes. The social context in which these two behaviors are initiated and
      associated has not been studied. METHODS: Data from a standardized questionnaire
      to measure the prevalence and practices related to cigarettes and narguileh
      consumption in a representative sample of 1097 children in grade 9 were extracted
      and analyzed for elements of the social context in which consumption occurs.
      RESULTS AND DISCUSSION: Among surveyed children (mean age 14.6), 3.9% were
      "frequent" cigarette smokers (more than nine times ever). Presence of parents
      and/or siblings who smoke is a key factor for initiation. Narguileh use is a
      social phenomenon, rarely smoked alone (<4%) with 19% of the surveyed children
      being "frequent" narguileh smokers (more than nine times ever). Almost half of
      these students (42%) have all their friends smoking narguileh. CONCLUSIONS:
      Further analysis confirmed that narguileh use is now an accepted familial and
      social phenomenon, with restrictions apparently decreasing. These results
      necessitate drawing strategies to address this public health concern that is
      becoming more prevalent in Lebanon and elsewhere in the Middle East.

PMID- 23856395
TI  - Consensus recommendation for meningococcal disease prevention in children and
      adolescents in the Middle East region.
AB  - Facing the availability of the new generation of quadrivalent meningococcal
      conjugate vaccines (Menveo(r), Menactra(r) and others pending for license) and
      their recent implementation in Saudi Arabia, experts from 11 countries of the
      Middle East region met at a "Meningococcal Leadership Forum" (MLF), which took
      place in May 2010 in Dubai. The participants of the conference discussed the
      importance of introducing the concept of conjugate vaccines - especially for
      children and adolescents - and elaborated a consensus recommendation to support
      healthcare professionals and decision makers with their expertise. In experts'
      opinion, conjugate vaccines are the best choice for the prevention of
      meningococcal disease caused by serogroups A, C, W-135 and Y. As quadrivalent
      meningococcal conjugate vaccines are registered and available in the Middle East
      region, they should replace plain polysaccharide vaccines and be integrated in
      pediatric and adolescent vaccination schedules, including infant vaccination
      concomitantly with basic EPI vaccines when licensed. 

PMID- 23856396
TI  - Mean temperature and humidity variations, along with patient age, predict the
      number of visits for renal colic in a large urban Emergency Department: results
      of a 9-year survey.
AB  - BACKGROUND: A marked geographic variability has been reported in stone disease,
      partially attributed to the Mean Annual Temperature (MAT), as well as to the
      seasonal fluctuations of climatic conditions. Accordingly, peaks in Emergency
      Department (ED) visits for renal colic are commonplace during the summer.
      MATERIALS AND METHODS: The aim of this study was to assess the influence of day
      by-day climate changes on the number of visits as a result of renal colic in the
      ED (City of Parma, northern Italy, temperate continental climate). A total of
      10,802 colic episodes were retrieved from the database during a period of
      3286days (January 2002 to December 2010). RESULTS: The analysis of the data
      confirms a peak of renal colic cases during the summer, especially in July
      (maximum number of 4.1 cases of renal colic per day), and a winter nadir (minimum
      number of 2.7 cases of renal colic per day, in February). The linear regression
      analysis shows a high and significant correlation between the mean number of
      cases of renal colic per day and both the mean daily temperature (positive
      association, R=0.93; p<0.0001) and the mean daily humidity (negative association,
      R=-0.82; p<0.0001). The influence of temperature and humidity on the incidence of
      renal colic cases varied widely among age groups, the highest incidence seen in
      patients aged between 30 and 40years, and the lowest seen for those aged <20 and
      >70years of age. CONCLUSION: The combined data suggest that the hot and dry
      climate would favor an acceleration of the process of stone formation, which
      seems more pronounced in the older population.

PMID- 23856397
TI  - Why are inaccurate tuberculosis serological tests widely used in the Indian
      private healthcare sector? A root-cause analysis.
AB  - Serological tests for tuberculosis are inaccurate and WHO has recommended against
      their use. Although not used by the Revised National TB Control Programme
      (RNTCP), serodiagnostics are widely used in the private sector in India. A root
      cause analysis was undertaken to determine why serological tests are so popular,
      and seven root causes were identified that can be grouped into three categories:
      technical/medical, economic, and regulatory. Technical/medical: RNTCP's current
      low budget does not allow scale-up of the newer, WHO-endorsed technologies. Thus,
      under the RNTCP, most patients have access to only smear microscopy, a test that
      is insensitive and underused in the private sector. Because there is no accurate,
      validated, point-of-care test for TB, serological tests meet a perceived need
      among doctors and patients. Economic: While imported molecular or liquid culture
      tests are too expensive, there are no affordable Indian versions on the market,
      leaving serological tests as the main alternative. Although serological tests are
      inaccurate, various players along the value chain profit from their use, and this
      sustains a market for these tests. Regulatory: TB tests are poorly regulated and
      a large number of serological kits are on the market. Private healthcare in
      general is poorly regulated, and doctors in the private sector are outside the
      scope of RNTCP and do not necessarily follow standard guidelines. A clear
      understanding of these realities should facilitate market-based strategies that
      can help replace serological tests with accurate, validated tools. 

PMID- 23856398
TI  - Tooth loss in institutionalized coronary heart disease patients of Punjab
      Institute of Cardiology, Lahore, Pakistan.
AB  - OBJECTIVE: To observe frequency and possible association of tooth loss with
      prevalent coronary heart disease in Pakistani population. METHODOLOGY:
      Angiographically determined coronary heart disease (CHD) patients of Punjab
      Institute of Cardiology, Lahore, Pakistan, and healthy individuals were enrolled
      for status of tooth loss. RESULTS: Nine hundred and thirty six CHD patients and
      595 healthy subjects with mean age of 51.9+/-8.4years were examined. Mean (+/-SD)
      tooth loss was significantly (P?0.001) higher in cardiac patients (9.8+/-9.2)
      than healthy subjects (6.8+/-6.9) with odds ratio (OR)=1.543 (95%CI=1.985-2.851).
      Tooth loss was significantly (P?0.001) associated with CHD males and females and
      cardiac patients with diabetes and smoking. After adjustment of age, gender,
      diabetes and smoking, subjects with CHD were more likely to have higher tooth
      loss. CONCLUSION: Tooth loss was significantly associated with prevalent CHD
      independent of classic risk factors of age, gender, smoking and diabetes in this
      study sample.

PMID- 23856399
TI  - Patterns of antituberculous drug resistance in Eastern Saudi Arabia: a 7-year
      surveillance study from 1/2003 to 6/2010.
AB  - OBJECTIVE: To examine the patterns of antituberculous drug resistance of
      Mycobacterium tuberculosis in patients with pulmonary and extra-pulmonary
      tuberculosis in the Eastern province of the Kingdom of Saudi Arabia. METHODS:
      This is a retrospective study of antibiotic susceptibility of 1681 non-repetitive
      M. tuberculosis isolates from 1/2003 to 6/2010. RESULTS: Of the total patients,
      41% (n=687) were Saudis and 59% (n=994) were non-Saudis. The pulmonary and extra
      pulmonary specimens constituted 68% (n=1148) and 32% (n=533), respectively. The
      incidence of resistance was 15.5% to one or more of anti-tuberculosis drugs. The
      resistance rates to first-line drugs were as follows: streptomycin (10.4%), INH
      (9.8%), rifampicin (1.5%) and ethambutol (1.0%). Multi-drug resistant
      tuberculosis was present in 1.4% (n=24) of the sample. CONCLUSION: INH resistance
      in this study was relatively high, whereas the rate of MDR-TB was low. A rate of
      MDR-TB observed in this study was 1.4%. Thus, an empiric four-drug therapy is
      required to treat patients with tuberculosis in this area of Saudi Arabia.

PMID- 23856400
TI  - Infertility in women after childhood cancer.

PMID- 23856401
TI  - Infertility, infertility treatment, and achievement of pregnancy in female
      survivors of childhood cancer: a report from the Childhood Cancer Survivor Study
      cohort.
AB  - BACKGROUND: Previous studies have shown decreased pregnancy rates and early
      menopause in female cancer survivors; however, infertility rates and reproductive
      interventions have not been studied. We investigated infertility and time to
      pregnancy in female childhood cancer survivors, and analysed treatment
      characteristics associated with infertility and subsequent pregnancy. METHODS:
      The Childhood Cancer Survivor Study (CCSS) is a cohort study including 5 year
      cancer survivors from 26 Canadian and US institutions who were younger than 21
      years at the time of diagnosis between Jan 1, 1970, and Dec 31, 1986, and a
      sibling control group. We included women aged 18-39 years who had ever been
      sexually active. We gathered demographic, medical, and reproductive data via a
      baseline questionnaire, and quantified exposure to alkylating agents and
      radiation therapy. Self-reported infertility, medical treatment for infertility,
      time to first pregnancy in survivors and siblings, and the risk of infertility in
      survivors by demographic, disease, and treatment variables were analysed.
      FINDINGS: 3531 survivors and 1366 female sibling controls who enrolled between
      Nov 3, 1992, and April 4, 2004, were included. Compared with their siblings,
      survivors had an increased risk (relative risk [RR] 1.48 [95% CI 1.23-1.78];
      p<0.0001) of clinical infertility (ie, >1 year of attempts at conception without
      success), which was most pronounced at early reproductive ages (RR 2.92 [95% CI
      1.18-7.20], p=0.020, in participants <=24 years; 1.61 [1.05-2.48], p=0.029, in
      those aged 25-29 years; and 1.37 [1.11-1.69], p=0.0035, in those aged 30-40
      years). Despite being equally likely to seek treatment for infertility, survivors
      were less likely than were their siblings to be prescribed drugs for treatment of
      infertility (0.57 [95% CI 0.46-0.70], p<0.0001). Increasing doses of uterine
      radiation and alkylating agent chemotherapy were strongly associated with
      infertility. Although survivors had an increased time to pregnancy compared with
      their siblings (p=0.032), 292 (64%) of 455 participants with self-reported
      clinical infertility achieved a pregnancy. INTERPRETATION: A more comprehensive
      understanding of infertility after cancer is crucial for counselling and decision
      making about future conception attempts and fertility preservation. FUNDING:
      National Cancer Institute, American Lebanese Syrian Associated Charities, Swim
      Across America.

PMID- 23856402
TI  - Coal and tire burning mixtures containing ultrafine and nanoparticulate materials
      induce oxidative stress and inflammatory activation in macrophages.
AB  - Ultra-fine and nano-particulate materials resulting from mixtures of coal and non
      coal fuels combustion for power generation release to the air components with
      toxic potential. We evaluated toxicological and inflammatory effects at cellular
      level that could be induced by ultrafine/nanoparticles-containing ashes from
      burning mixtures of coal and tires from an American power plant. Coal fly ashes
      (CFA) samples from the combustion of high-S coal and tire-derived fuel, the
      latter about 2-3% of the total fuel feed, in a 100-MW cyclone utility boiler,
      were suspended in the cell culture medium of RAW 264.7 macrophages. Cell
      viability, assessed by MTT reduction, SRB incorporation and contrast-phase
      microscopy analysis demonstrated that CFA did not induce acute toxicity. However,
      CFA at 1mg/mL induced an increase of approximately 338% in intracellular TNF
      alpha, while release of this proinflammatory cytokine was increased by 1.6-fold.
      The expression of the inflammatory mediator CD40 receptor was enhanced by 2-fold,
      the receptor for advanced glycation endproducts (RAGE) had a 5.7-fold increase
      and the stress response protein HSP70 was increased nearly 12-fold by CFA at
      1mg/mL. Although CFA did not induce cell death, parameters of oxidative stress
      and reactive species production were found to be altered at several degrees, such
      as nitrite accumulation (22% increase), DCFH oxidation (3.5-fold increase),
      catalase (5-fold increase) and superoxide dismutase (35% inhibition) activities,
      lipoperoxidation (4.2 fold-increase) and sulfhydryl oxidation (40% decrease in
      free SH groups). The present results suggest that CFA containing ultra-fine and
      nano-particulate materials from coal and tire combustion may induce sub-chronic
      cell damage, as they alter inflammatory and oxidative stress parameters at the
      molecular and cellular levels, but do not induce acute cell death. 

PMID- 23856403
TI  - Effect of acanthocephalan infection on metal, total protein and metallothionein
      concentrations in European chub from a Sava River section with low metal
      contamination.
AB  - In the present study, the importance of considering fish intestinal parasites
      i.e. the acanthocephalans in metal exposure assessment was estimated under low
      metal contamination conditions. Two acanthocephalan species, Pomphorhynchus
      laevis and Acanthocephalus anguillae were examined in 59 specimens of European
      chub (Squalius cephalus L.) sampled at 5 locations along the Sava River, Croatia.
      Concentrations of essential (Cu, Mn) and non-essential (Ag, Cd, Pb) metals were
      higher in intestinal parasites than chub gastrointestinal tissue, but levels of
      essential metals Fe and Zn were comparable or lower in parasites, respectively.
      The highest accumulation in both acanthocephalan species was found for non
      essential metals and followed the order: Ag>Pb>Cd. Higher infection intensity
      with P. laevis allowed us to present their spatial metal distribution and
      evaluate the influence of P. laevis on metal levels and sub-cellular biological
      responses (total protein and metallothionein levels) in the host infected with P.
      laevis. Even in the river section with low metal contamination, parasitism
      affected metal levels, resulting in lower Cu, Cd and Pb concentrations in chub
      infected with P. laevis than in uninfected chub. Although total protein and
      metallothionein levels remained constant in infected and uninfected chub,
      acanthocephalans should be considered a potential confounding factor in metal
      exposure assessments. Moreover, P. laevis-chub system can be suggested as an
      appropriate tool in biomonitoring, since in both species increased Cu and Cd
      concentrations towards the downstream locations were found. Higher Cu and Cd
      levels in P. laevis suggest acanthocephalans to be sensitive bioindicators if low
      metal levels have to be detected. 

PMID- 23856404
TI  - In situ application of stir bar sorptive extraction as a passive sampling
      technique for the monitoring of agricultural pesticides in surface waters.
AB  - Grab sampling and automated sampling are not suitable or logistically too
      constraining for the monitoring of pesticides in dynamic streams located in
      agricultural watersheds. In this work, we applied stir bar sorptive extraction
      (SBSE) Twisters(r) directly in two small rivers of a French vineyard (herein
      referred to as "passive SBSE"), for periods of one or two weeks during a month,
      for the passive sampling of 19 agricultural pesticides. We performed qualitative
      and semi-quantitative comparisons of the performances of passive SBSE firstly to
      automated sampling coupled to analytical SBSE, and secondly to the polar organic
      chemical integrative sampler (POCIS), a well-known passive sampler for
      hydrophilic micropollutants. Applying passive SBSE in river waters allowed the
      quantification of more pesticides and in greater amounts than analytical SBSE as
      shown for samples collected concurrently. Also, passive SBSE and POCIS proved to
      be complementary techniques in terms of detected molecules; but only passive SBSE
      was able to integrate a concentration peak triggered by a quick flood event that
      lasted 5 h. Passive SBSE could be an interesting tool for the monitoring of
      moderately hydrophobic to hydrophobic organic micropollutants in changing
      hydrosystems. In this purpose, further studies will focus on the accumulation
      kinetics of target pesticides and the determination of their sampling rates.

PMID- 23856405
TI  - Characterisation of one H6N6 influenza virus isolated from swine in China.
AB  - There is multiple evidence that swine may act as a vessel for the generation of
      novel influenza A viruses. In this study, we have analyzed the evolution and
      pathogenicity of one strain of H6N6 influenza virus isolated from swine with
      clinical signs of infection in China. Although phylogenetic analysis revealed
      that this virus might originate from domestic ducks, pathogenicity experiments
      indicated that the virus replicated in mice without prior adaptation. These
      findings suggest that the virus has transmitted from ducks to swine in China, and
      replicated in mammalian hosts without prior adaptation, which may pose a threat
      to both veterinary and public health. 

PMID- 23856406
TI  - Neuroprotective role of superoxide dismutase 1 in retinal ganglion cells and
      inner nuclear layer cells against N-methyl-d-aspartate-induced cytotoxicity.
AB  - The N-methyl-d-aspartate (NMDA) receptor-induced apoptosis is implicated in the
      pathological mechanisms of neural tissues, increasing the release of reactive
      oxygen species (ROS), resulting in a type of apoptotic cell death called
      excitotoxicity. Although intrinsic mechanisms to remove ROS, such as antioxidant
      enzymes, are provided by the tissue, the association between NMDA-induced
      excitotoxicity and antioxidative enzymes is not well understood. In this study,
      we focused on superoxide dismutase 1 (SOD1), an antioxidant enzyme, and
      investigated the role of SOD1 in the NMDA-induced neuronal cell death in the
      retina. NMDA was intravitreally injected into wild-type (WT) and SOD1 total knock
      out (SOD1-deficient) mice. The number of TUNEL-positive cells in the retinal
      ganglion cell layer (GCL) and inner nuclear layer (INL) counted in the retinal
      sections and flatmount retinas were significantly higher in the SOD1-deficient
      mice than the WT mice after NMDA injection. Visual function assessed by dark
      adapted electroretinogram (ERG) showed that the amplitudes of a-wave, b-wave, and
      oscillatory potential 2 were significantly reduced in the NMDA-injected SOD1
      deficient mice. The level of ROS in the GCL and INL, measured using
      dihydroethidium, and the number of positive cells for gamma-H2AX, a marker for
      DNA double strand breaks, and 8-OHdG, a marker for DNA oxidation, in the GCL were
      significantly increased in the SOD1-deficient mice after NMDA injection. We also
      measured mRNA and protein levels of SOD1 and SOD2 in the retina of WT mice, to
      find that mRNA and protein levels of SOD1, but not SOD2, were significantly
      reduced after NMDA injection. SOD1 deficiency exacerbated NMDA-induced damage to
      the inner retinal neurons, and NMDA reduced SOD1 levels in the retina of WT mice.
      Therefore, SOD1 protected retinal neurons against NMDA-induced retinal
      neurotoxicity, and NMDA-induced SOD1 reduction may be involved in neuronal
      vulnerability to excitotoxicity. 

PMID- 23856407
TI  - Meigs syndrome presenting with axillary vein thrombosis and lymphadenopathy: a
      case report.
AB  - INTRODUCTION: Meigs syndrome is a rare condition, occurring in less than 1% of
      ovarian tumors and has the characteristic features of a benign ovarian tumor,
      ascites and a pleural effusion. We present a case of Meigs syndrome in a young
      patient presenting initially with an axillary vein thrombosis and local
      lymphadenopathy. CASE PRESENTATION: A 28-year-old Caucasian woman presented with
      a short history of right arm swelling and shortness of breath as a result of an
      axillary vein thrombosis and pulmonary embolus.The initial assessment also
      demonstrated right axillary and subclavian lymphadenopathy, a pleural effusion,
      ascites and a large ovarian mass. Serum levels of the tumor markers human
      chorionic gonadotropin and alpha-fetoprotein were normal and the CA-125 level was
      only moderately elevated.The combination of thrombosis, lymphadenopathy and an
      ovarian mass raised the possibility of a disseminated malignancy potentially an
      epithelial ovarian cancer, a germ cell tumor or an ovarian sex cord-stromal
      tumor.Surgery, performed after a short period of anticoagulation, demonstrated a
      13.5cm ovarian cellular fibroma of low malignant potential. Postoperatively the
      patient made an excellent recovery and the ascites, pleural effusion and
      lymphadenopathy all resolved promptly. CONCLUSIONS: In Meigs syndrome the
      classical findings of ascites, pleural effusion in combination with an ovarian
      mass can mimic disseminated malignancy but resolve spontaneously after surgery.
      In this current case, the patient also had lymphadenopathy and venous thrombosis,
      two other findings that are frequently associated with malignancy and was acutely
      unwell at presentation.It is unclear if the thrombosis and lymphadenopathy were
      simply coincidental or shared the same etiology as the ascites and pleural
      effusion. This case indicates that Meigs syndrome may on occasion present with
      additional findings that can further mimic disseminated malignancy and may lead
      to diagnostic uncertainty.

PMID- 23856408
TI  - The dynamic expression of extraembryonic marker genes in the beetle Tribolium
      castaneum reveals the complexity of serosa and amnion formation in a short germ
      insect.
AB  - Most insect embryos develop with two distinct extraembryonic membranes, the
      serosa and the amnion. In the insect beetle Tribolium the early origin of the
      serosa within the anterior blastoderm is well established but the origin of the
      amnion is still debated. It is not known whether this tissue develops from a
      blastodermal precursor or originates de novo later from embryonic tissue during
      embryogenesis. We undertook an in-depth analysis of the spatio-temporal
      expression pattern profile of important extraembryonic membrane marker genes with
      emphasis on early blastoderm development in Tribolium. The amnion marker iroquois
      (Tc-iro) was found co-expressed with the serosa marker zerknullt1 (Tc-zen1)
      during early blastoderm formation in an anterior cap domain. This domain later
      resolved into two adjacent domains that likely represent the precursors of the
      serosa and the amnion. In addition, we found the hindsight ortholog in Tribolium
      (Tc-hnt) to be a serosa-specific marker. Surprisingly, decapentaplegic (Tc-dpp)
      expression was not seen as a symmetric cap domain but detected asymmetrically
      first along the DV- and later also along the AP-axis. Moreover, we found a
      previously undescribed domain of phosphorylated MAD (pMAD) protein in anterior
      ventral serosal cells. This is the first study showing that the anterior-lateral
      part of the amnion originates from the anterior blastoderm while the precursor of
      the dorsal amnion develops later de novo from a dorsal-posterior region within
      the differentiated blastoderm. 

PMID- 23856410
TI  - Endowing carbon nanotubes with biological and biomedical properties by chemical
      modifications.
AB  - The scope of nanotechnology is gaining importance in biology and medicine. Carbon
      nanotubes (CNTs) have emerged as a promising tool due to their unique properties,
      high specific surface area, and capacity to cross biological barriers. These
      properties offer a variety of opportunities for applications in nanomedicine,
      such as diagnosis, disease treatment, imaging, and tissue engineering.
      Nevertheless, pristine CNTs are insoluble in water and in most organic solvents;
      thereby functionalization of their surface is necessary to increase
      biocompatibility. Derivatization of CNTs also gives the possibility to conjugate
      different biological and bioactive molecules including drugs, proteins, and
      targeting ligands. This review focuses on the chemical modifications of CNTs that
      have been developed to impart specific properties for biological and medical
      purposes. Biomolecules can be covalently grafted or non-covalently adsorbed on
      the nanotube surface. In addition, the inner core of CNTs can be exploited to
      encapsulate drugs, nanoparticles, or radioactive elements. 

PMID- 23856409
TI  - Microfluidics-assisted in vitro drug screening and carrier production.
AB  - Microfluidic platforms provide several unique advantages for drug development. In
      the production of drug carriers, physical properties such as size and shape, and
      chemical properties such as drug composition and pharmacokinetic parameters, can
      be modified simply and effectively by tuning the flow rate and geometries. Large
      numbers of carriers can then be fabricated with minimal effort and with little to
      no batch-to-batch variation. Additionally, cell or tissue culture models in
      microfluidic systems can be used as in vitro drug screening tools. Compared to in
      vivo animal models, microfluidic drug screening platforms allow for high
      throughput and reproducible screening at a significantly lower cost, and when
      combined with current advances in tissue engineering, are also capable of
      mimicking native tissues. In this review, various microfluidic platforms for drug
      and gene carrier fabrication are reviewed to provide guidelines for designing
      appropriate carriers. In vitro microfluidic drug screening platforms designed for
      high-throughput analysis and replication of in vivo conditions are also reviewed
      to highlight future directions for drug research and development. 

PMID- 23856411
TI  - Carbon nanotubes in neuroregeneration and repair.
AB  - In the last decade, we have experienced an increasing interest and an improved
      understanding of the application of nanotechnology to the nervous system. The aim
      of such studies is that of developing future strategies for tissue repair to
      promote functional recovery after brain damage. In this framework, carbon
      nanotube based technologies are emerging as particularly innovative tools due to
      the outstanding physical properties of these nanomaterials together with their
      recently documented ability to interface neuronal circuits, synapses and
      membranes. This review will discuss the state of the art in carbon nanotube
      technology applied to the development of devices able to drive nerve tissue
      repair; we will highlight the most exciting findings addressing the impact of
      carbon nanotubes in nerve tissue engineering, focusing in particular on neuronal
      differentiation, growth and network reconstruction. 

PMID- 23856413
TI  - BioMEMS in drug delivery.
AB  - The drive to design micro-scale medical devices which can be reliably and
      uniformly mass produced has prompted many researchers to adapt processing
      technologies from the semiconductor industry. By operating at a much smaller
      length scale, the resulting biologically-oriented microelectromechanical systems
      (BioMEMS) provide many opportunities for improved drug delivery: Low-dose
      vaccinations and painless transdermal drug delivery are possible through
      precisely engineered microneedles which pierce the skin's barrier layer without
      reaching the nerves. Low-power, low-volume BioMEMS pumps and reservoirs can be
      implanted where conventional pumping systems cannot. Drug formulations with
      geometrically complex, extremely uniform micro- and nano-particles are formed
      through micromolding or with microfluidic devices. This review describes these
      BioMEMS technologies and discusses their current state of implementation. As
      these technologies continue to develop and capitalize on their simpler
      integration with other MEMS-based systems such as computer controls and
      telemetry, BioMEMS' impact on the field of drug delivery will continue to
      increase. 

PMID- 23856412
TI  - Peroxidase-mediated biodegradation of carbon nanotubes in vitro and in vivo.
AB  - As a result of their unique electronic, optical, and mechanical properties,
      carbon nanotubes (CNTs) have been implemented in therapeutic and imaging
      applications. In an idealized situation, CNTs would be disposed of after they
      transport their theranostic payloads. Biodegradation represents an attractive
      pathway for the elimination of CNT carriers post-delivery and may be integral in
      catalyzing the release of the cargo from the delivery vehicle. Accordingly,
      recent research efforts have focused on peroxidase-driven biodegradation of CNTs.
      In this review, we not only summarize recent efforts to biodegrade CNTs in the
      test tube, in vitro, and in vivo, but also attempt to explore the fundamental
      parameters underlying degradation. Encouraged by the in vivo results obtained to
      date, we envision a future, where carbon-based nano-containers, which are
      specifically designed to target organs/cells, deliver their cargo, and biodegrade
      via peroxidase-driven mechanism, will represent an attractive therapeutic
      delivery option in nanomedicine. 

PMID- 23856414
TI  - Predictive models for type 2 diabetes onset in middle-aged subjects with the
      metabolic syndrome.
AB  - OBJECTIVE: To investigate the predictive value of different biomarkers for the
      incidence of type 2 diabetes mellitus (T2DM) in subjects with metabolic syndrome.
      METHODS: A prospective study of 525 non-diabetic, middle-aged Lithuanian men and
      women with metabolic syndrome but without overt atherosclerotic diseases during a
      follow-up period of two to four years. We used logistic regression to develop
      predictive models for incident cases and to investigate the association between
      various markers and the onset of T2DM. RESULTS: Fasting plasma glucose (FPG),
      body mass index (BMI), and glycosylated haemoglobin can be used to predict
      diabetes onset with a high level of accuracy and each was shown to have a
      cumulative predictive value. The estimated area under the receiver-operating
      characteristic curve (AUC) for this combination was 0.92. The oral glucose
      tolerance test (OGTT) did not show cumulative predictive value. Additionally,
      progression to diabetes was associated with high values of aortic pulse-wave
      velocity (aPWV). CONCLUSION: T2DM onset in middle-aged metabolic syndrome
      subjects can be predicted with remarkable accuracy using the combination of FPG,
      BMI, and HbA1c, and is related to elevated aPWV measurements.

PMID- 23856415
TI  - Immune cell profile in infants' lung tissue.
AB  - Little is known about the normal immune cell profile in the lungs of infants
      without pulmonary disease. Normal lung samples obtained at autopsy of 10 infants
      that died either due to incidental or inflicted causes or non-pulmonary diseases
      were stained for antibodies against B and T lymphocytes, macrophages, NK cells,
      cytotoxic cells, dendritic cells and mast cells. Cells were quantified in the
      airway epithelial layer, inner layer (between the epithelium and the outer smooth
      muscle border), outer layer (between the outer smooth muscle border and the
      external limits of the airway) and alveolar septa. Basement membrane or alveolar
      septa lengths were assessed by image analysis. Results were expressed as
      cells/mm. The median age of patients was 6.8 months, ranging from 11 to 840 days.
      The inner layer of the airways was the region with the smallest density of cells.
      There was a predominance of cells related to the innate immunity such as CD56+,
      Granzyme B+ and CD68+ cells in the epithelial layer and alveolar parenchyma. The
      outer layer and the lung parenchyma presented the highest cellular density. There
      were very few CD4+ T cells or dendritic cells in most of the lung compartments.
      The numbers of CD3+ T and granzyme B+ cells correlated positively with age. There
      was a compartmentalization of immune cells along airways and parenchyma, which
      may be related to the development of innate and acquired lung defense mechanisms.

PMID- 23856416
TI  - Anatomische Gesellschaft from 1933 to 1950: a professional society under
      political strain - the Benninghoff papers.
AB  - The Anatomische Gesellschaft (anatomical society, AG) was founded in Germany in
      1886 as an international society and remains the main organizing body of German
      anatomists to this day. A previous study of the history of the AG during National
      Socialism (NS) was based on the published proceedings of the AG and drew the
      preliminary conclusion that the "AG did not follow the path of preemptive
      obedience toward the new rulers" in contrast to some other professional
      societies. However, it was noted that archival sources were needed to support
      this conclusion and to illustrate the decision process within the society. Such
      sources are now available in the estate papers of Alfred Benninghoff, a leading
      anatomist at the time. His correspondence supports the previous finding that the
      AG was able to maintain its international character, thereby enabling it to avoid
      the active exclusion of "non-Aryan" members. The papers also confirm that the AG
      did not defend its vulnerable members as valiantly as the official narrative
      suggests, a fact illustrated in a controversy surrounding Martin Heidenhain. The
      interactions and conflicts between the leaders of the AG can now be
      reconstructed, i.e. between the secretary of the AG Heinrich von Eggeling,
      Benninghoff and Hermann Stieve. The Benninghoff documents also refer to a meeting
      of a subsection of the AG in November 1942, at which a disturbing radicalization
      of some anatomists developed. Finally, the papers reflect the political realities
      for German professionals trying to re-establish their science in a country
      divided into four occupation zones. 

PMID- 23856417
TI  - Down-regulation of histamine-induced endothelial cell activation as potential
      anti-atherosclerotic activity of peptides from Spirulina maxima.
AB  - Histamine, a potent inflammatory mediator, has been known to cause the
      pathogenesis of atherosclerosis. In this sense, two bioactive peptides P1
      (LDAVNR; 686Da) and P2 (MMLDF; 655Da) purified from gastric enzymatic hydrolysate
      of Spirulina maxima were examined for their protective effects against early
      atherosclerotic responses induced by histamine in EA.hy926 endothelial cells.
      Interestingly, both P1 and P2 exhibited inhibitory activities on the production
      and expression of IL-6 and MCP-1. Furthermore, P1 and P2 inhibited the production
      of adhesion molecules including P-selectin and E-selectin, and thus reducing in
      vitro cell adhesion of monocyte onto endothelial cells. In addition, the
      production of intracellular reactive oxygen species was observed to reduce in the
      presence of P1 or P2. Notably, the inhibitory activities of P1 and P2 were found
      due to down-regulating Egr-1 expression via histamine receptor and PKCdelta
      dependent MAPKs activation pathway. These results suggest that peptides P1 and P2
      from S. maxima are effective to suppress histamine-induced endothelial cell
      activation that may contribute to the prevention of early atherosclerosis. 

PMID- 23856418
TI  - Hypoxia preconditioned bone marrow mesenchymal stem cells promote liver
      regeneration in a rat massive hepatectomy model.
AB  - INTRODUCTION: Bone marrow mesenchymal stem cells (BMMSCs) have been reported to
      facilitate liver regeneration after toxic injuries. However, the effect of BMMSCs
      on liver regeneration after massive hepatectomy is barely studied. Here we
      explored whether infusion of BMMSCs promotes liver regeneration in a rat massive
      hepatectomy model. METHODS: Hypoxia preconditioning was achieved by culturing
      BMMSCs under a hypoxia environment. Then 85% hepatectomy was performed and
      hypoxia or normoxia preconditioned BMMSCs were infused into the portal vein. A
      group of rats received vascular endothelial growth factor (VEGF) neutralizing
      antibody perioperatively, and underwent 85% hepatectomy and a subsequent infusion
      of hypoxia preconditioned BMMSCs to verify the role of VEGF in the effects of
      BMMSCs on liver regeneration. Liver samples were collected and liver regeneration
      was evaluated postoperatively. RESULTS: Hypoxia preconditioning enhanced the
      expression of VEGF in BMMSCs in vitro. Infusion of BMMSCs promoted proliferation
      of hepatocytes, reflected by elevated cyclin D1 expression and proliferating cell
      nuclear antigen-positive hepatocytes. However, BMMSC infusion did not improve the
      serum albumin level, liver weight/body weight ratio, and survival after
      operation. Infusion of hypoxia preconditioned BMMSCs significantly elevated
      cyclin D1, proliferating cell nuclear antigen-positive hepatocytes, liver
      weight/body weight ratio, and survival compared with normoxia preconditioned
      BMMSCs, accompanied by an increased serum albumin level. The level of VEGF in
      liver homogenate was much higher in hypoxia preconditioned BMMSC-treated animals
      than in other groups. In addition, the perioperative injection of VEGF
      neutralizing antibody significantly blocked the therapeutic effects of hypoxia
      preconditioned BMMSCs on liver injury and regeneration in this model. CONCLUSION:
      Hypoxia preconditioned BMMSCs enhanced liver regeneration after massive
      hepatectomy in rats, possibly by upregulating the level of VEGF.

PMID- 23856419
TI  - Pathogenesis of mitral valve disease in mucopolysaccharidosis VII dogs.
AB  - Mucopolysaccharidosis VII (MPS VII) is due to the deficient activity of beta
      glucuronidase (GUSB) and results in the accumulation of glycosaminoglycans (GAGs)
      in lysosomes and multisystemic disease with cardiovascular manifestations. The
      goal here was to determine the pathogenesis of mitral valve (MV) disease in MPS
      VII dogs. Untreated MPS VII dogs had a marked reduction in the histochemical
      signal for structurally-intact collagen in the MV at 6 months of age, when mitral
      regurgitation had developed. Electron microscopy demonstrated that collagen
      fibrils were of normal diameter, but failed to align into large parallel arrays.
      mRNA analysis demonstrated a modest reduction in the expression of genes that
      encode collagen or collagen-associated proteins such as the proteoglycan decorin
      which helps collagen fibrils assemble, and a marked increase for genes that
      encode proteases such as cathepsins. Indeed, enzyme activity for cathepsin B
      (CtsB) was 19-fold normal. MPS VII dogs that received neonatal intravenous
      injection of a gamma retroviral vector had an improved signal for structurally
      intact collagen, and reduced CtsB activity relative to that seen in untreated MPS
      VII dogs. We conclude that MR in untreated MPS VII dogs was likely due to
      abnormalities in MV collagen structure. This could be due to upregulation of
      enzymes that degrade collagen or collagen-associated proteins, to the
      accumulation of GAGs that compete with proteoglycans such as decorin for binding
      to collagen, or to other causes. Further delineation of the etiology of abnormal
      collagen structure may lead to treatments that improve biomechanical properties
      of the MV and other tissues.

PMID- 23856420
TI  - The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC
      expression in murine glycogen storage disease type Ia.
AB  - Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6
      phosphatase-alpha (G6Pase-alpha or G6PC) manifest impaired glucose homeostasis
      characterized by fasting hypoglycemia, growth retardation, hepatomegaly,
      nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious
      recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing
      human G6Pase-alpha have been independently developed. One is a single-stranded
      vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the
      other is a double-stranded vector containing a shorter 382-bp minimal G6PC
      promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct
      comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to
      determine the best vector to take forward into clinical trials. We show that the
      rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-alpha
      expression, achieved greater reduction in hepatic glycogen accumulation, and led
      to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our
      results indicated that additional control elements in the rAAV8-GPE vector
      outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency,
      and that the rAAV8-GPE vector is the current choice for clinical translation in
      human GSD-Ia. 

PMID- 23856422
TI  - Population structure and the burden of disease in the United Arab Emirates.
AB  - To carry out their duties more effectively, health care professionals in the UAE
      often ask about the population structure and the main causes of mortality and
      morbidity in the country. This paper summarizes what is known about these topics
      drawing on secondary data sources that are available in the public domain,
      including census data, population estimates, births and deaths, proportionate
      mortality, age-standardized mortality rates and disability adjusted life-years.
      There are inconsistencies and flaws in some of this data which this paper will
      highlight and attempt to explain. Since 2005, the UAE population has grown
      substantially owing to high natural growth and high net inward migration and is
      currently estimated to be about 8.2million. In 2008, injuries, heart disease,
      neoplasms and cerebrovascular disease accounted for 57% of deaths, and this is
      well known. Less is reported about the risk of death, disease, injury and
      disability. The population of the UAE is diverse, and there are variations in
      mortality and morbidity risk by age-group, sex and nationality. The authors
      recommend improvements in the timeliness, completeness and consistency of data.
      They conclude that better data will encourage more analysis which will generate
      health intelligence leading to health improvement for the UAE population. 

PMID- 23856421
TI  - Congenital disorder of glycosylation due to DPM1 mutations presenting with
      dystroglycanopathy-type congenital muscular dystrophy.
AB  - Congenital disorders of glycosylation (CDG) are rare genetic defects mainly in
      the post-translational modification of proteins via attachment of carbohydrate
      chains. We describe an infant with the phenotype of a congenital muscular
      dystrophy, with borderline microcephaly, hypotonia, camptodactyly, severe motor
      delay, and elevated creatine kinase. Muscle biopsy showed muscular dystrophy and
      reduced alpha-dystroglycan immunostaining with glycoepitope-specific antibodies
      in a pattern diagnostic of dystroglycanopathy. Carbohydrate deficient transferrin
      testing showed a pattern pointing to a CDG type I. Sanger sequencing of DPM1
      (dolichol-P-mannose synthase subunit 1) revealed a novel Gly > Val change c.455G
      > T missense mutation resulting in p.Gly152Val) of unknown pathogenicity and
      deletion/duplication analysis revealed an intragenic deletion from exons 3 to 7
      on the other allele. DPM1 activity in fibroblasts was reduced by 80%, while
      affinity for the substrate was not depressed, suggesting a decrease in the amount
      of active enzyme. Transfected cells expressing tagged versions of wild type and
      the p.Gly152Val mutant displayed reduced binding to DPM3, an essential, non
      catalytic subunit of the DPM complex, suggesting a mechanism for pathogenicity.
      The present case is the first individual described with DPM1-CDG (CDG-Ie) to also
      have clinical and muscle biopsy findings consistent with dystroglycanopathy.

PMID- 23856423
TI  - Putting surveillance data into context: the role of health care utilization
      surveys in understanding population burden of pneumonia in developing countries.
AB  - BACKGROUND: Surveillance is essential to estimating the global burden of
      pneumonia, yet differences in surveillance methodology and health care-seeking
      behaviors limit inter-country comparisons. METHODS: Results were compared from
      community surveys measuring health care-seeking for pneumonia defined as: (1)
      cough and difficulty breathing for ?2days; or, (2) provider-diagnosed pneumonia.
      Surveys were conducted in six sites in Guatemala, Kenya and Thailand; these sites
      also conduct, active, hospital- and population-based disease surveillance for
      pneumonia. RESULTS: Frequency of self-reported pneumonia during the preceding
      year ranged from 1.1% (Thailand) to 6.3% (Guatemala) and was highest in children
      aged <5years and in urban sites. The proportion of persons with pneumonia who
      sought hospital-based medical services ranged from 12% (Guatemala, Kenya) to 80%
      (Thailand) and was highest in children <5years of age. Hospitals and private
      provider offices were the most common places where persons with pneumonia sought
      health care. The most commonly cited reasons for not seeking health care were:
      (a) mild illness; (b) already recovering; and (3) cost of treatment. CONCLUSIONS:
      Health care-seeking patterns varied widely across countries. Using results from
      standardized health care utilization surveys to adjust facility-based
      surveillance estimates of pneumonia allows for more accurate and comparable
      estimates.

PMID- 23856424
TI  - On the reliability of self-reported health: evidence from Albanian data.
AB  - This paper investigates the reliability of self-assessed measures of health using
      panel data collected in Albania by the World Bank in 2002, 2003 and 2004 through
      the Living Standard Measurement Study project. As the survey includes questions
      on a self-assessed measure of health and on more objective health problems, both
      types of information are combined with a view to understanding how respondents
      change their answers to the self-reported measures over time. Estimates from
      random effects ordered Probit models show that differences in self-reported
      subjective health between individuals are much more marked than those over time,
      suggesting a strong state dependence in subjective health status. The empirical
      analysis also reveals respondent consistency, from both a subjective and an
      objective viewpoint. Self-reported health is much more influenced by permanent
      shocks than by more transitory illness or injury. 

PMID- 23856425
TI  - Progress on human papillomavirus (HPV) infection and cervical cancer prevention
      in sub-Saharan Africa: highlights of the 27th International Papillomavirus
      Conference in Berlin, 17-22 September 2011.
AB  - Highlights of the International Papillomavirus Conference in Berlin, 17-22
      September 2011. 

PMID- 23856426
TI  - Pneumococcal nasopharyngeal colonization.

PMID- 23856427
TI  - Percutaneous endoscopic gastrostomy in children--issues remain.

PMID- 23856428
TI  - Rationale and clinical use of multitargeting anticancer agents.
AB  - Human solid tumors contain genetically distinct subpopulations of tumor cells
      that can be enriched under selective pressure of specific treatments. This
      heterogeneous nature reflects the dynamism of drug response and it represents a
      fundamental driver of resistance. Moreover, the complexity of cancer disease is
      increased by the activity of cross-talking, redundant signaling pathways, escape
      pathways and compensatory events, which triggers activation of secondary growth
      and survival. Broad multi-targeted approaches are requested to overcome a
      complex, heterogeneous, and dynamic disease such as cancer. 

PMID- 23856429
TI  - Functional magnetic resonance imaging in rodents: an unique tool to study in vivo
      pharmacologic neuromodulation.
AB  - When new compounds targeting the brain are developed, it is important to assess
      both the acute and chronic effects on brain functioning. This can be done non
      invasively using a technique called functional magnetic resonance imaging (fMRI).
      This review discusses the possibilities of both stimulation-based and resting
      state fMRI to study pharmacological modulations of the rodent brain. Moreover,
      attention is given to the use of anesthetics which could importantly influence
      the outcome of both techniques. 

PMID- 23856430
TI  - Angiotensin II type 1 receptor blocker-induced immune thrombocytopenia: a case
      report.
AB  - INTRODUCTION: The development of thrombocytopenia after a dose increase in
      losartan and subsequently after switching the patient to valsartan is reported.
      CASE PRESENTATION: A 61-year-old Caucasian man presented with epistaxis and
      gingival bleeding of three weeks duration. Laboratory evaluation revealed a
      hemoglobin level of 144g/L, a leukocyte count of 16.2*109 cells/L (72.51%
      neutrophils, 20.1% lymphocytes, 6.8% monocytes, 0.4% eosinophils, 0.2% bands),
      and a platelet count of 15.0*109 cells/L. Flow cytometry of his peripheral blood
      showed normal CD4:CD8 ratio and no evidence of any lymphoproliferative disorder.
      A peripheral smear showed decreased platelets with a few areas of clumping. Four
      weeks before presentation to the emergency room, his losartan dose was increased
      to 100mg once daily due to continuously elevated blood pressure readings. He had
      been maintained on losartan 50mg once daily for five years and previous routine
      laboratory measurements revealed a baseline platelet count of 248.0*109
      cells/L.The patient began receiving an oral prednisone taper and his platelet
      count returned to a stable value of >200*109 cells/L. Because there was no other
      probable cause, he was thought to have developed immune thrombocytopenia from the
      increased losartan dose. Losartan was discontinued and one week later he was
      switched to valsartan 160mg once daily.Forty-seven days after starting valsartan,
      the patient presented once again to the emergency room with intermittent
      epistaxis and gingival bleeding while brushing his teeth of two weeks duration.
      Laboratory measurement revealed a platelet count of 37*109 cells/L. Valsartan was
      held and another prednisone taper was initiated. The patient's platelet count
      recovered upon valsartan discontinuation and in four weeks, his platelet count
      improved to 214*109 cells/L. CONCLUSIONS: A 61-year-old Caucasian man developed
      immune thrombocytopenia after an increase in losartan dose and developed immune
      thrombocytopenia again after he was switched to valsartan.

PMID- 23856431
TI  - In-vitro/In-vivo comparison of leuprolide acetate release from an in-situ forming
      plga system.
AB  - A poly (lactide-co-glycolide) (PLGA) implant was used to control the release
      profile of leuprolide acetate (LA) drug. The system is an in-situ polymeric
      precipitation system. And the formulation consisted of PLGA polymer, LA drug and
      N-methyl-2-pyrrolidon solvent with no additives. First, the formulation was
      injected into PBS solution for in-vitro studies and then it was administered to
      the animal models (female rats) for in-vivo release studies. The release profiles
      of leuprolide acetate were measured by UV spectrophotometry for a period of 28
      days. The initial burst release of LA was 14% in in-vitro whereas it was 7% in in
      vivo. In-vitro and in-vivo release profiles of LA had similar trends after 72
      hours. However, the rate of LA release was slower in-vivo. This might be
      attributed to the limited diffusion process of solvent and the drug molecules.
      This could be due to presence of an additional pressure caused by the surrounding
      tissue and also the presence of small amount of water between cells in the
      subcutaneous site. Cross-section and surface of the implants were studied via
      scanning electron microscopy. Morphology of both in-vitro and in-vivo implants
      confirmed the release behaviours. No toxicity effects were reported in the
      histopathological assay. Furthermore, the pharmacological analysis showed more
      inactive ovaries due to release of LA. 

PMID- 23856432
TI  - Who's feeding baby? Non-maternal involvement in feeding and its association with
      dietary intakes among infants and toddlers.
AB  - This study examined non-maternal involvement in feeding during the first 2 years
      of life and its association with breastfeeding duration, early introduction of
      complementary foods, and dietary intakes of selected foods and beverages. Data
      were from the Infant Care, Feeding and Risk of Obesity Study, a cohort of 217 low
      income, African-American mother-infant dyads, followed from 3 to 18 months
      postpartum. Non-maternal caregivers (NMCs) were defined as persons involved in
      feeding an infant/toddler 50% or more of the total daily feedings. Use of any NMC
      and the type of NMC was tabulated for each study visit (3, 6, 9, 12, and 18
      months). At each time point, more than half of all households reported a NMC.
      Fathers, grandmothers, and licensed childcare providers were the most common
      types of NMCs. In longitudinal models adjusted for confounding variables, NMC use
      was associated with a decreased likelihood of continued breastfeeding, and an
      increased likelihood of infants and toddlers consuming juice or whole fruit.
      Given the high prevalence of non-maternal involvement in feeding, interventions
      targeting multiple family members are warranted as they are likely to be more
      effective than those targeting the mother alone.

PMID- 23856433
TI  - Validity and reliability of the Food-Life Questionnaire. Short form.
AB  - Measures of beliefs and attitudes towards food need to be valid, and easy to use
      and interpret. The present study aimed to establish the validity and reliability
      of a short-form of the Food-Life Questionnaire (FLQ). Participants (247 females;
      118 males), recruited in South Australia, completed a questionnaire in 2012
      incorporating the original FLQ, a revised short form (FLQ-SF), and measures of
      food choice and consumption. Validity (construct, criterion-related, and
      incremental) and reliability (internal consistency and short-form) were assessed.
      Factor analysis established that short-form items loaded onto five factors
      consistent with the original FLQ and explained 60% of variance. Moderate
      correlations were observed between the FLQ-SF and a measure of food choices
      (r=.32-.64), and the FLQ-SF predicted unhealthy food consumption over and above
      the full FLQ demonstrating criterion-related and incremental validity
      respectively. The final FLQ-SF included 21 items and had a Cronbach's alpha of
      .75. Short-form reliability was established with correlations between
      corresponding subscales of the FLQ and FLQ-SF ranging from r=.64-.84. Overall,
      the FLQ-SF is brief, psychometrically robust, and easy to administer. It should
      be considered an important tool in research informing public policies and
      programs that aim to improve food choices. 

PMID- 23856434
TI  - Proactive coping moderates the dietary intention-planning-behavior path.
AB  - BACKGROUND: The study examines psychosocial mechanisms in dietary change using
      the health action process approach (HAPA) as its theoretical backdrop. Previous
      studies have supported the model in the domain of dietary behaviors but it has
      not yet been studied in China. OBJECTIVE: Dietary planning is assumed to mediate
      between intentions and dietary behaviors. However, among individuals scoring low
      on proactive coping, this mediation might fail. Therefore, an extension of the
      model by including proactive coping is examined. METHODS: Psychometric scales
      were administered at two points in time, three months apart, to 240 young Chinese
      men and women. Intentions, outcome expectancies, risk perception, action self
      efficacy, and proactive coping were assessed at Time 1, whereas planning, coping
      self-efficacy, and dietary behavior were measured at Time 2. RESULTS: Structural
      equation models replicated previous evidence on the validity of the HAPA.
      Intentions and planning mediated sequentially the effects of outcome expectancies
      and self-efficacy on dietary behaviors. Moreover, the inclusion of proactive
      coping yielded no main effects, but an interaction between intentions and
      proactive coping on dietary planning. The intention-planning-behavior chain was
      moderated by proactive coping which means that this connection operates only well
      when individuals are proactive. CONCLUSIONS: A combination of proactive coping
      and the motivation to eat healthy foods facilitates dietary planning which, in
      turn, benefits corresponding behaviors.

PMID- 23856435
TI  - Two cells are better than one: optimizing stem cell survival by co-grafting
      "helper" cells that offer regulated trophic support.

PMID- 23856436
TI  - Genetically modified mesenchymal stem cells (MSCs) promote axonal regeneration
      and prevent hypersensitivity after spinal cord injury.
AB  - Neurotrophins and the transplantation of bone marrow-derived stromal cells (MSCs)
      are both candidate therapies targeting spinal cord injury (SCI). While some
      studies have suggested the ability of MSCs to transdifferentiate into neural
      cells, other SCI studies have proposed anti-inflammatory and other mechanisms
      underlying established beneficial effects. We grafted rat MSCs genetically
      modified to express MNTS1, a multineurotrophin that binds TrkA, TrkB and TrkC,
      and p75(NTR) receptors or MSC-MNTS1/p75(-) that binds mainly to the Trk
      receptors. Seven days after contusive SCI, PBS-only, GFP-MSC, MSC-MNTS1/GFP or
      MSC-MNTS1/p75(-)/GFP were delivered into the injury epicenter. All transplanted
      groups showed reduced inflammation and cystic cavity size compared to control SCI
      rats. Interestingly, transplantation of the MSC-MNTS1 and MSC-MNTS1/p75(-), but
      not the naive MSCs, enhanced axonal growth and significantly prevented cutaneous
      hypersensitivity after SCI. Moreover, transplantation of MSC-MNTS1/p75(-)
      promoted angiogenesis and modified glial scar formation. These findings suggest
      that MSCs transduced with a multineurotrophin are effective in promoting cell
      growth and improving sensory function after SCI. These novel data also provide
      insight into the neurotrophin-receptor dependent mechanisms through which
      cellular transplantation leads to functional improvement after experimental SCI. 

PMID- 23856437
TI  - Risk of transmission of Trypanosoma cruzi by wild Triatoma infestans (Hemiptera:
      Reduviidae) in Bolivia supported by the detection of human blood meals.
AB  - We analyzed the food sources of Bolivian wild Triatoma infestans (the main vector
      of Chagas disease in this country), to assess the role of these populations in
      the epidemiological context of Chagas disease. Ninety-eight blood meals were
      identified by heteroduplex assay and sequencing. Most of them were from wild
      mammals but surprisingly 27 were from humans. This brings to light the occurrence
      of human-vector contacts at risk of Trypanosoma cruzi transmission in the wild
      environment by highly infected insects. 

PMID- 23856438
TI  - Evolution of the use of noninvasive mechanical ventilation in chronic obstructive
      pulmonary disease in a Spanish region, 1997-2010.
AB  - INTRODUCTION: Noninvasive mechanical ventilation (NIV) appeared in the 1980s as
      an alternative to invasive mechanical ventilation (IMV) in patients with acute
      respiratory failure. We evaluated the introduction of NIV and the results in
      patients with acute exacerbation of chronic obstructive pulmonary disease in the
      Region of Murcia (Spain). SUBJECTS AND METHODS: A retrospective observational
      study based on the minimum basic hospital discharge data of all patients
      hospitalised for this pathology in all public hospitals in the region between
      1997 and 2010. We performed a time trend analysis on hospital attendance, the use
      of each ventilatory intervention and hospital mortality through joinpoint
      regression. RESULTS: We identified 30.027 hospital discharges. Joinpoint
      analysis: downward trend in attendance (annual percentage change [APC]=-3.4, 95%
      CI: - 4.8; -2.0, P <.05) and in the group without ventilatory intervention (APC=
      4.2%, -5.6; -2.8, P <.05); upward trend in the use of NIV (APC=16.4, 12.0; 20. 9,
      P <.05), and downward trend that was not statistically significant in IMV (APC=
      4.5%, -10.3; 1.7). We observed an upward trend without statistical significance
      in overall mortality (APC=0.5, -1.3; 2.4) and in the group without intervention
      (APC=0.1, -1.6; 1.9); downward trend with statistical significance in the NIV
      group (APC=-7.1, -11.7; -2.2, P <.05) and not statistically significant in the
      IMV group (APC=-0,8, -6, 1; 4.8). The mean stay did not change substantially.
      CONCLUSIONS: The introduction of NIV has reduced the group of patients not
      receiving assisted ventilation. No improvement in results was found in terms of
      mortality or length of stay.

PMID- 23856439
TI  - Comorbidities and health status in individuals with and without COPD in five
      Latin American cities: the PLATINO study.
AB  - INTRODUCTION: Comorbidities are common in patients with chronic obstructive
      pulmonary disease (COPD), and have a significant impact on health status and
      prognosis. The PLATINO study provides data on self-reported comorbidities and
      perceived health status in COPD subjects. METHODS: PLATINO is a population-based
      study on COPD prevalence in five Latin American cities. COPD diagnosis was
      defined by GOLD criteria (FEV1/FVC<.70 post-bronchodilator). Information was
      collected on the following comorbidities: heart disease, hypertension, diabetes,
      cerebrovascular disease, peptic ulcer and asthma. Health status was evaluated
      using the SF-12 questionnaire, derived from the question: "In general, would you
      say your health is excellent, very good, good, fair or poor?". A simple
      comorbidity score was calculated by adding the total number of comorbid
      conditions. RESULTS: Of a total population of 5314individuals, 759 had COPD.
      Reported comorbidities by decreasing frequency were: any cardiovascular disease,
      hypertension, peptic ulcer, heart disease, diabetes, cerebrovascular disease,
      asthma and lung cancer. COPD patients had a higher comorbidity score and
      prevalence of lung cancer (P<.0001) and asthma (P<.0001), as well as a higher
      tendency to have hypertension (P=.0652) and cerebrovascular disease (P=.0750).
      Factors associated with comorbidities were age, body mass index (BMI) and female
      gender. The number of comorbidities increased as the health status deteriorated.
      CONCLUSIONS: In the PLATINO population-based study, COPD individuals had an
      increased number of comorbidities. Age, female gender and higher BMI were the
      factors associated with comorbidity in these patients. Comorbid conditions were
      associated with impaired health status, independently of the COPD status.

PMID- 23856441
TI  - Puerarin, isolated from Pueraria lobata (Willd.), protects against hepatotoxicity
      via specific inhibition of the TGF-beta1/Smad signaling pathway, thereby leading
      to anti-fibrotic effect.
AB  - Recently, the TGF-beta1/Smad signaling pathway has been investigated in the
      pathogenesis of hepatofibrosis, and pharmacological treatment of liver fibrosis
      targeted this pathway to determine its contribution to the inhibition of fibrotic
      development. Importantly, ethnopharmacology-derived Pueraria lobata has been
      reported to effectively reverse the fibrotic process in the liver. In the present
      study, we performed dimethylnitrosamine (DMN)-induced liver fibrosis in rats to
      assess the benefits of puerarin (PR), which was isolated from Pueraria lobata
      (Willd.), on ECM-derived hepatocytes associated with the TGF-beta1/Smad pathway.
      Our results showed that the serum levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN), type III
      precollagen (PCIII) and type IV collagen (CIV) were significantly reduced by PR
      treatment, while hepatic homogenates showed decreased levels of hydroxyproline
      (Hyp) and collagen I (Col I). Masson's trichrome staining indicated that the DMN
      induced liver fibrosis was alleviated. In addition, the protein expression levels
      of transforming growth factor-beta l (TGF-beta l), smad2, smad3, alpha-SMA and
      TIMP-1 were downregulated specifically by PR treatment, whereas the protein
      expression levels of smad7 and MMP-1 were upregulated. Furthermore, we evaluated
      the PR-mediated inhibitory effect on TGF-beta1-treated proliferation and
      activation in a rat liver stellate cell line (HSC-T6). These data resulted in
      inhibition of the cell growth of HSC-T6 in a dose-dependent manner and a
      reduction in TbetaRI, smad2 and smad3 expressed proteins in the presence of PR on
      TGF-beta1-treated HSC-T6 cells, while smad7 levels were downregulated. Taken
      together, these findings identify a unique effect for PR-regulation of the TGF
      beta1/Smad pathway in blocking fibrotic development and provide a promising
      strategy for hepatofibrosis treatment. 

PMID- 23856440
TI  - The measles virus phosphoprotein interacts with the linker domain of STAT1.
AB  - The measles virus (MV) phosphoprotein (P) and V proteins block the interferon
      (IFN) response by impeding phosphorylation of the signal transducer and activator
      of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how
      STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the
      linker, the Src-homology 2 domain (SH2), or the transactivation domain had
      reduced or abolished phosphorylation through JAK1 after IFN treatment. Other
      mutants, mainly localized in the linker, failed to interact with P as documented
      by the lack of interference with nuclear translocation. Thus the functional
      footprint of P on STAT1 localizes mainly to the linker domain; there is also some
      overlap with the STAT1 phosphorylation functional footprint on the SH2 domain.
      Based on these observations, we discuss how the MV-P might operate to inhibit the
      JAK/STAT pathway. 

PMID- 23856442
TI  - Omega-3 polyunsaturated fatty acids in the treatment of hypertriglyceridaemia.
AB  - Hypertriglyceridaemia (HTG) is an independent risk factor for cardiovascular
      disease; high-risk patients with HTG, such as those with metabolic syndrome or
      diabetes, may benefit from hypolipidaemic therapies. Several lipid-lowering drugs
      act by reducing triglyceride (TG) levels, including fibrates, nicotinic acid and
      omega-3 fatty acids. The omega-3 polyunsaturated fatty acids eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) dose-dependently reduce plasma TG
      levels; the effect tends to be greater in patients with higher TG levels at
      baseline. Evidence from clinical trials suggests that EPA+DHA doses of >= 2 g/day
      are required to achieve significant effects. The optimal TG-lowering doses of
      EPA+DHA are 3-4 g/day, with little evidence to support lipid-altering efficacy of
      doses of EPA and DHA <1g/day. Predicted changes in fasting serum TG levels at the
      recommended dietary intakes of EPA and/or DHA of 200-500 mg/day are -3.1% to 
      7.2%. Reductions of plasma TG levels at the optimal doses are from 25-35% up to
      45% in the presence of severely elevated TG levels (>= 500 mg/dl; >= 5.65
      mmol/l), along with a reduction in non-high-density lipoprotein-cholesterol (non
      HDL-C) and an increase in HDL-C. This observation has also been confirmed in
      statin-treated patients.

PMID- 23856443
TI  - Discrepancies in vessel sizing between angiography and intravascular ultrasound
      varies according to the vessel evaluated.
AB  - BACKGROUND/OBJECTIVES: Quantitative coronary analysis (QCA) of the coronary
      artery and stent size may be influenced by anatomical location in relation to
      both calibration point and the X-ray tube. The impact of this phenomenon on
      lesion assessment is undetermined. METHODS: In total, 427 consecutive patients
      who underwent PCI with intravascular ultrasound (IVUS)-guidance were enrolled.
      The minimum stent diameter (MSD) was measured using QCA (MSDQCA) and IVUS
      (MSDIVUS) analysis. We used reference objects positioned at a different height
      from the X-ray source to validate our approach. RESULTS: A statistically positive
      moderate correlation was observed between MSDQCA and MSDIVUS (r=0.649, p=0.001).
      The mean MSDQCA and MSDIVUS were 3.04+/-0.49 mm and 2.68+/-0.47 mm respectively.
      The difference between MSDQCA and MSDIVUS of >0.75 mm was more frequently
      observed in the LCx rather than in the LAD (7.4% in the LAD vs. 24.3% in the LCx,
      p=0.001). The discrepancy between the MSDQCA and MSDIVUS for the LCx was larger
      than for the LAD, and tended to be larger than for the RCA (13.3% vs. 18.5%,
      p=0.05 and 18.5% vs. 14.5%, p=0.17). A discrepancy >20% was more frequently
      observed in the small (<=2.5 mm) than in the large MSDIVUS group (52.7% vs.
      25.1%, p=0.001). This discrepancy was more common in the LCx than in the LAD or
      RCA (48.6% vs. 30.9% vs. 31.2%, p=0.03). CONCLUSIONS: Assessment of the MSDQCA is
      more likely to overestimate in the LCx than in the LAD, particularly when the
      MSDIVUS is <2.5 mm. Therefore, we should be less aggressive in oversizing
      balloons and stents based on QCA for the LCx or small vessel intervention.

PMID- 23856444
TI  - Hypercholesterolemia blocked sevoflurane-induced cardioprotection against
      ischemia-reperfusion injury by alteration of the MG53/RISK/GSK3beta signaling.
AB  - BACKGROUND: Recent studies have demonstrated that volatile anesthetic
      preconditioning confers myocardial protection against ischemia-reperfusion (IR)
      injury through activation of the reperfusion injury salvage kinase (RISK)
      pathway. As RISK has been shown to be impaired in hypercholesterolemia, we
      investigate whether anesthetic-induced cardiac protection was maintained in
      hypercholesterolemic rats. METHODS: Normocholesteolemic or hypercholesterolemic
      rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. Animals
      received 2.4% sevoflurane during three 5 min periods with and without PI3K
      antagonist wortmannin (10 MUg/kg, Wort) or the ERK inhibitor PD 98059 (1 mg/kg,
      PD). The infarct size, apoptosis, p-Akt, p-ERK1/2, p-GSK3beta were determined.
      RESULTS: Two hundred and six rats were analyzed in the study. In the healthy
      rats, sevoflurane significantly reduced infarct size by 42%, a phenomenon
      completely reversed by wortmannin and PD98059 and increased the phosphorylation
      of Akt, ERK1/2 and their downstream target of GSK3beta. In the
      hypercholesterolemic rats, sevoflurane failed to reduce infarct size and increase
      the phosphorylated Akt, ERK1/2 and GSK3beta. In contrast, GSK inhibitor SB216763
      conferred cardioprotection against IR injury in healthy and hypercholesterolemic
      hearts. CONCLUSIONS: Hyperchoesterolemia abrogated sevoflurane-induced
      cardioprotection against IR injury by alteration of upstream signaling of
      GSK3beta and acute GSK inhibition may provide a novel therapeutic strategy to
      protect hypercholesterolemic hearts against IR injury.

PMID- 23856445
TI  - Reentry mechanisms and ablation of ECG-typical atrial flutters involving the cavo
      tricuspid isthmus and the proximal coronary sinus.
AB  - AIM: Reentry circuits of a rare typical atrial flutter (AFL) involving the cavo
      tricuspid isthmus (CTI) and proximal coronary sinus (CS) are described based on
      electrophysiological data and effects of radiofrequency (RF). METHODS AND
      RESULTS: Twelve patients with ECG-typical AFL in whom entrainment demonstrated
      that CTI and proximal CS were both part of the circuit were included. Initial RF
      target was CTI in 8 patients and proximal CS in 4. Success was defined as AFL
      termination/noninducibility. After CTI ablation, AFL cycle length (CL) increased
      in all: AFL persisted in 3, while in the other 5 AFL was interrupted but
      subsequently induced with the same morphology; before induction CTI bi
      directional block was validated; success was obtained at the CS, targeting
      fragmented atrial potentials (APs). In those with first ablation at CS, AFL was
      interrupted in 3 with no AFL inducibility; in 1 AFL persisted with CL
      prolongation and was terminated at CTI. Two reentry patterns were identified: in
      5 patients the inter-atrial septum as well as the mid-distal CS were outside of
      the circuit, while the CTI, proximal CS and Bachmann's bundle zone were inside,
      suggesting a left atrial component; in 1 patient electrophysiological mapping
      suggested an intra-CS circuit component. RF was successful in all without
      recurrence. CONCLUSION: Electrophysiological mapping and RF effects suggest a
      continuum between the CTI and proximal CS in rare cases with ECG-typical AFL. RF
      inside the proximal CS, targeting fragmented APs, should be considered in any
      patient in whom CTI ablation failed to interrupt a typical AFL.

PMID- 23856446
TI  - [Isolation of Geosmithia argillacea in a cystic fibrosis patient].
AB  - We report the case of an 11-year-old child with cystic fibrosis where Geosmithia
      argillacea has been isolated from sputum. This is a filamentous fungus (mold)
      recently described as emergent infectious agent in cystic fibrosis patients. In
      our case, the presence of G. argillacea was not associated with clinical
      disorder. However, recent evidence shows that it can be responsible for very
      serious invasive infection, especially in chronic granulomatous disease and may
      be, after lung transplantation. 

PMID- 23856447
TI  - [Fungal and bacterial contamination of 30 general practitioners' consultation
      room in Franche-Comte (eastern France)].
AB  - OBJECTIVE: To evaluate the level of microbial contamination of general pratice
      environment. METHODS: Ten points, including air, water and surfaces were sampled
      in general practitioner's consultation room of 30 general practices in Franche
      Comte region (eastern France). For each sample, a global microbial count was
      assessed as well as the presence of potential pathogen microorganisms:
      Aspergillus fumigatus, Staphylococcus aureus, Pseudomonas aeruginosa, and
      Enterobacteriaceae. RESULTS: We note that 66.3% of the samples (n=202) were on
      the target level (<51 ufc/25 cm (2), <101 ufc/m(3), <100 ufc/mL in total
      bacteria, without pathogenic species and without A. fumigatus respectively on
      surfaces, air and water, without isolation of coliforme bacteria or P. aeruginosa
      for 100mL of water). A. fumigatus, S. aureus, P. aeruginosa and
      Enterobacteriaceae were recovered in 8.0%, 2.1%, 0.7%, 0% respectively. However,
      66.7% of air sampling were positive to A. fumigatus with 2 to 12 cfu/m(3).
      CONCLUSION: This study shows a low level of bacterial contamination of general
      practitioner's consultation room. A. fumigatus frequency in air samples seems
      equivalent to that found in housing without air treatment.

PMID- 23856448
TI  - A mucormycosis case treated with a combination of caspofungin and amphotericin B.
AB  - Mucormycosis is a rare, invasive and fatal disease that occurs mainly in diabetes
      mellitus patients with uncontrolled blood glucose levels or in immunocompromised
      patients. The mortality rate of this disease is as high as 25 to 80%, despite
      aggressive surgical treatment and antifungal therapy. This high mortality
      requires alternative treatment approaches. The accepted treatment modality of
      invasive mucormycosis are amphotericin B lipid formulations. Although
      echinocandins generally show no activity against Mucorales, it was shown that
      Rhizopus oryzae expressed the target enzyme for echinocandins, 1,3-beta-glucan
      synthase. Additionally, there are some experimental studies in a diabetic mouse
      model and case reports regarding the effects of caspofungin. In this report, we
      present a rhinocerebral mucormycosis case treated with liposomal amphotericin B
      and caspofungin. There was regression of the patient's clinical and radiological
      condition with the addition of caspofungin, but she died due to discontinuation
      of her treatment and reasons other than mucormycosis. 

PMID- 23856449
TI  - Association between iron status and white blood cell counts in African
      schoolchildren of the North-West Province, South Africa.
AB  - Iron deficiency with or without anemia is associated with increased
      susceptibility to infection owing to impaired immune function; this study aimed
      to examine the associations between markers of iron status and white blood cell
      counts in African schoolchildren. This cross-sectional study is part of the
      larger BeForMi study done in the North-West province of South Africa. A total of
      556 African schoolchildren (aged 7-10 years) were recruited from the three
      schools participating in the BeForMi multiple micronutrient intervention study.
      Demographic information of the children was obtained from their
      parents/caregivers/guardians in the language of choice using validated
      questionnaires. Anthropometric indices (weight and height), iron status
      parameters, hematological parameters (hemoglobin (Hb), red blood cell count
      (RBC), total and differential white blood cell counts) were measured using
      standard procedures. No significant gender differences were observed in most of
      the iron markers and hematological parameters except in C-reactive protein (CRP)
      (p=0.004) and eosinophils (p=0.042) which were higher in boys while RBC (p=0.018)
      and Hb (p=0.023) levels were higher in girls. No relationships were observed
      between the different iron markers and differential white blood cell counts. A
      positive correlation was observed between serum ferritin (SF) and CRP in girls
      only (r=0.336, p<0.01), and a positive correlation between SF and mean cell
      volume (MCV) in boys only (r=0.197, p<0.01). In both genders, no correlations
      were observed between the different iron markers and the differential white blood
      cell counts. The study revealed no associations between iron status and
      differential white blood cell counts in children that participated in the BeForMi
      study calling for more studies to be done in the area of the significance of iron
      supplementation in healthy children.

PMID- 23856450
TI  - The use of epidemiological measures to estimate the impact of primary prevention
      interventions on CHD, stroke and cancer outcomes: experiences from Herefordshire,
      UK.
AB  - BACKGROUND: CHD, stroke and cancers are the major causes of mortality in the UK
      and are responsible for significant amounts of morbidity and healthcare costs.
      This study examines the proportion of CHD, stroke and cancer owing to specific
      risk factors in Herefordshire, UK. It estimates the population impact of a number
      of interventions being implemented to reduce these risk factors, through the NHS
      Health Check program and the Herefordshire Health Improvement Plan. The present
      study also aims to demonstrate the value of epidemiological measures in providing
      evidence-based public health information in policy-making to aid decision makers
      when prioritizing investments and optimal use of resources. METHODS: The
      epidemiological measures-'Population Attributable Risk' and 'Population Impact
      Measures'-were used to assess the impact of interventions to reduce the burden of
      CHD, stroke and cancer. RESULTS: Implementation of the NHS Health Check program
      will prevent 63 CHD events, 90 MI events and 125 stroke events, and one lung
      cancer over a period of 5 years. Reducing specific risk factors by 5% annually
      through the Health Improvement Plan will prevent 65 CHD events, 25 MI events, 140
      stroke events, four lung cancer, one breast cancer and four colorectal cancer
      cases in Herefordshire if targets are met over a period of 5 years. CONCLUSION:
      Physical inactivity and obesity are the major causes of CHD and stroke events
      (incidence and mortality) in Herefordshire. Their impact is greater than the
      combined effect of hypercholesterolemia and hypertension. Epidemiological
      measures used in this study proved to be excellent tools in providing evidence
      based public health information. Their use is strongly recommended to support
      prioritization of primary prevention interventions.

PMID- 23856451
TI  - Global teaching and training initiatives for emerging cohort studies.
AB  - A striking disparity exists across the globe, with essentially no large-scale
      longitudinal studies ongoing in regions that will be significantly affected by
      the oncoming non-communicable disease epidemic. The successful implementation of
      cohort studies in most low-resource research environments presents unique
      challenges that may be aided by coordinated training programs. Leaders of
      emerging cohort studies attending the First World Cohort Integration Workshop
      were surveyed about training priorities, unmet needs and potential cross-cohort
      solutions to these barriers through an electronic pre-workshop questionnaire and
      focus groups. Cohort studies representing India, Mexico, Nigeria, South Africa,
      Sweden, Tanzania and Uganda described similar training needs, including on-the
      job training, data analysis software instruction, and database and bio-bank
      management. A lack of funding and protected time for training activities were
      commonly identified constraints. Proposed solutions include a collaborative cross
      cohort teaching platform with web-based content and interactive teaching methods
      for a range of research personnel. An international network for research
      mentorship and idea exchange, and modifying the graduate thesis structure were
      also identified as key initiatives. Cross-cohort integrated educational
      initiatives will efficiently meet shared needs, catalyze the development of
      emerging cohorts, speed closure of the global disparity in cohort research, and
      may fortify scientific capacity development in low-resource settings. 

PMID- 23856452
TI  - Perinatal and family factors associated with preadolescence overweight/obesity in
      Greece: the GRECO study.
AB  - OBJECTIVE: To explore associations of perinatal and family factors with
      preadolescence overweight and obesity in a sample of Greek schoolchildren.
      METHODS: A nationwide cross-sectional study among 2093 students (10.9 +/- 0.72
      years, 44.9% boys) and their parents were conducted. Anthropometric (e.g.,
      height, weight, mother's body mass index (BMI) at the time of the study and at
      conception), socio-demographic (e.g., age, education, socio-economic status),
      diet and other major lifestyle characteristics (e.g., smoking, alcohol intake,
      physical activity and inactivity) and perinatal factors (e.g., breast- and
      formula-feeding) were collected with validated questionnaires. Height and weight
      of students were measured. Overweight/obesity was classified using IOTF cut-offs.
      Multivariable logistic and linear regression analyses were used to identify major
      independent factors of overweight/obesity among preadolescents and factors
      related with the percentage change of mother's BMI, respectively. RESULTS:
      Increased age at pregnancy [odds ratios (OR)=0.95, 95% Confidence Interval (CI):
      0.93-0.97], higher BMI at conception (OR=1.17, 95% CI: 1.12-1.22) and heavy
      smoking (OR = 2.02, 95% CI: 1.23-3.33) were positively associated with child's
      overweight/obesity status. Moreover, mother's age and TV viewing, indicating
      inactivity, were the strongest factors of the percentage increase in mother's BMI
      (b +/- se = 0.23 +/- 0.07, p = 0.002; b +/- se=0.32 +/- 0.10, p = 0.002,
      respectively). CONCLUSIONS: Preadolescent obesity is associated with mother's pre
      pregnancy weight, age and heavy smoking at conception and mother's BMI change
      after gestation.

PMID- 23856453
TI  - The effects of angiotensin II signaling pathway in the systolic response to acute
      stretch in the normal and ischemic myocardium.
AB  - Acute myocardial stretch elicits a biphasic increase in contractility: an
      immediate increase, known as Frank-Starling mechanism (FSM), followed by a
      progressive increase, regarded as slow force response (SFR). In this study, we
      characterized the contractile response to acute stretch from 92 to 100% Lmax in
      rabbit papillary muscles (n=86) under normoxic and ischemic conditions, and its
      modulation by angiotensin II signaling pathway. Under normoxia, the FSM was
      independent of Na(+)/H(+)-exchanger, reverse mode of Na(+)/Ca(2+)-exchanger (r
      NCX), AT1 receptor, AT2 receptor and PKC. Regarding the SFR, it was mediated by
      AT1 receptor activation and its downstream effectors PKC, Na(+)/H(+)-exchanger
      and r-NCX. Ischemia negatively impacted on the FSM and abolished the SFR, with
      the muscles exhibiting a time-dependent decline in contractility. Under ischemic
      conditions, FSM was not influenced by AT1 and AT2 receptors or PKC activation.
      AT1 receptor antagonism rescued the progressive deterioration in contractility,
      an effect partially dependent on AT2 receptor activation. 

PMID- 23856454
TI  - The anti-inflammatory potential of neuropeptide FF in vitro and in vivo.
AB  - Neuropeptide FF (NPFF) has many functions in regulating various biological
      processes. However, little attention has been focused on the anti-inflammatory
      effect of this peptide. In the present study, the in vitro anti-inflammatory
      activity of NPFF in both primary peritoneal macrophages and RAW 264.7 macrophages
      was investigated. Our data showed that NPFF suppressed the nitric oxide (NO)
      production of macrophages in the inflammation process. RF9, a reported antagonist
      of NPFF receptors, completely blocked the NPFF-induced NO suppression, suggesting
      a NPFF receptors-mediated pathway is mainly involved. Down-regulation of the
      nitric oxide synthases significantly inhibited the NPFF-induced NO reduction,
      indicating the involvement of nitric oxide synthases. However, the nitric oxide
      synthases were not the only route by which NPFF modulated the NO levels of
      macrophages. Pharmacological antagonists of the NF-kappaB signal pathway also
      completely suppressed the NPFF-induced NO decline. Moreover, we also observed
      that NPFF is capable of blocking the LPS-induced nuclear translocation of p65 in
      macrophages, implying the involvement of the NF-kappaB signal pathway. Finally,
      we observed that NPFF markedly attenuated the carrageenan-induced mouse paw
      edema, indicating that NPFF is capable of exerting anti-inflammatory potency in
      vivo. Collectively, our findings reveal the potential role of NPFF in the anti
      inflammatory field both in vitro and in vivo, which will be helpful for the
      further exploitation of NPFF utility therapeutically. 

PMID- 23856455
TI  - A large gastrointestinal stromal tumor of the duodenum treated by partial
      duodenectomy with Roux-en-Y duodenojejunostomy: a case report.
AB  - INTRODUCTION: Duodenal gastrointestinal stromal tumors are uncommon and a
      relatively small subset of gastrointestinal stromal tumors whose optimal surgical
      procedure has not been well defined. Because submucosal spread and local lymph
      node involvement are infrequent in gastrointestinal stromal tumors, wide margins
      with routine lymph node dissection may not be required. Various surgical
      procedures for duodenal gastrointestinal stromal tumor, pancreatoduodenectomy,
      pancreas-sparing duodenectomy, segmental duodenectomy, or local resection, have
      been described depending on the size and exact site of the lesion. CASE
      PRESENTATION: We present the case of a 65-year-old African woman with a giant
      gastrointestinal stromal tumor involving the second and third portion of the
      duodenum successfully treated by partial duodenectomy with duodenojejunostomy.
      This surgical technique is ideal when a gastrointestinal stromal tumor does not
      involve the ampulla because it avoids a pancreatoduodenectomy, and has not been
      previously described for the management of this malignancy. Duodenal
      gastrointestinal stromal tumor should be suspected in any patient with a duodenal
      wall mass. CONCLUSIONS: Gastrointestinal stromal tumors of the duodenum should be
      suspected in any patient with a duodenal wall mass. Extramural growth and central
      ulceration with or without bleeding should alert the endoscopist to the
      possibility of a duodenal gastrointestinal stromal tumor diagnosis.

PMID- 23856456
TI  - Voltammetric behavior and determination of doxycycline in pharmaceuticals at
      molecularly imprinted and non-imprinted overoxidized polypyrrole electrodes.
AB  - In this paper, electrochemical behavior of a member of tetracycline group
      compounds doxycyline (DC) was investigated in 20, 30, 40% (v/v) acetonitrile
      (ACN)-water binary mixture at the pH of 2.0-4.0 prepared Britton-Robinson (BR)
      buffers, by the differential pulse voltammetric method (DPV). Voltammetric
      determination of DC was carried out using molecularly imprinted (MIP) and non
      imprinted polypyrrole (NIP) modified electrodes. Both types of electrode were
      prepared by the cyclic voltammetric method. The effect of the ACN-water ratio and
      pH, on the performance of the MIP electrode was investigated and optimized. The
      highest anodic signal of DC with MIP electrode was obtained in BR buffer solution
      was prepared in 30% (v/v) ACN-water at pH 2.0. The detection limit was determined
      as 4.35*10(-5)M (S/N=3). The method was also applied for electrochemical
      determination of DC in pharmaceutical samples. The recovery factors for
      Tetradox((r)) and Monodox((r)) were found 96.30%, 61.18% respectively with the
      relative standard deviations 0.46 and 0.54. The results of experiments using two
      commercial drugs showed that the MIP electrode can be used as a sensor to
      determine DC in pharmaceuticals. 

PMID- 23856457
TI  - Prognostic factors of infantile spasms: role of treatment options including a
      ketogenic diet.
AB  - OBJECTIVES: The aim of this study was to provide additional evidences on
      prognostic factors for infantile spasms and the possible role of a ketogenic
      diet. METHODS: A retrospective analysis was performed for patients with infantile
      spasms who had been followed up for more than 6months between January 2000 and
      July 2012 at Samsung Medical Center (Seoul, Republic of Korea). We analyzed the
      association between possible prognostic factors and seizure/developmental
      outcomes. RESULTS: Sixty-nine patients were included in this study and their mean
      follow-up duration was 52.5 (9-147) months. In the patients who had been followed
      up for more than 2years, 53.6% (n=30/57) remained seizure-free at the last visit.
      Sixty patients (86.9%) showed developmental delay at last follow-up. Forty-two
      patients (60.9%) became spasm-free with one or two antiepileptic drugs, one
      patient with epilepsy surgery for a tumor, and seven patients with a ketogenic
      diet after the failure of two or more antiepileptic drugs. The etiology and age
      of seizure onset were the significant prognostic factors. CONCLUSIONS: In this
      study, about 60% of the patients became spasm-free with vigabatrin and
      topiramate. Ketogenic diet increased the rate by 10% in the remaining
      antiepileptic drug resistant patients. However, 86.9% of the patients showed
      developmental delay, mostly a severe degree. Early diagnosis and prompt
      application of treatment options such as antiepileptic drugs, a ketogenic diet or
      epilepsy surgery can improve outcomes in patients with infantile spasms.

PMID- 23856458
TI  - Global 'bootprinting' reveals the elastic architecture of the yeast TFIIIB-TFIIIC
      transcription complex in vivo.
AB  - TFIIIB and TFIIIC are multi-subunit factors required for transcription by RNA
      polymerase III. We present a genome-wide high-resolution footprint map of TFIIIB
      TFIIIC complexes in Saccharomyces cerevisiae, obtained by paired-end sequencing
      of micrococcal nuclease-resistant DNA. On tRNA genes, TFIIIB and TFIIIC form
      stable complexes with the same distinctive occupancy pattern but in mirror image,
      termed 'bootprints'. Global analysis reveals that the TFIIIB-TFIIIC transcription
      complex exhibits remarkable structural elasticity: tRNA genes vary significantly
      in length but remain protected by TFIIIC. Introns, when present, are markedly
      less protected. The RNA polymerase III transcription terminator is flexibly
      accommodated within the transcription complex and, unexpectedly, plays a major
      structural role by delimiting its 3'-boundary. The ETC sites, where TFIIIC binds
      without TFIIIB, exhibit different bootprints, suggesting that TFIIIC forms
      complexes involving other factors. We confirm six ETC sites and report a new site
      (ETC10). Surprisingly, TFIIIC, but not TFIIIB, interacts with some centromeric
      nucleosomes, suggesting that interactions between TFIIIC and the centromere may
      be important in the 3D organization of the nucleus. 

PMID- 23856459
TI  - Creation of a Merkel cell polyomavirus small T antigen-expressing murine tumor
      model and a DNA vaccine targeting small T antigen.
AB  - BACKGROUND: Merkel cell polyomavirus (MCPyV) is a DNA virus expressing
      transcripts similar to the large T (LT) and small T (ST) transcripts of SV40,
      which has been implicated in the pathogenesis of Merkel cell carcinoma (MCC), a
      rare and highly aggressive neuroendocrine skin cancer. MCPyV LT antigen
      expression was found to be a requirement for MCC tumor maintenance and ST protein
      also likely contributes to the carcinogenesis of MCC. Previously, we have
      identified the probable immunodominant epitope of MCPyV LT and developed a DNA
      vaccine encoding this epitope linked to calreticulin. The LT-targeting DNA
      vaccine generated prolonged survival, decreased tumor size and increased LT
      specific CD8+ T cells in tumor-bearing mice. RESULTS: In this study, we developed
      a MCPyV ST-expressing tumor cell line from B16 mouse melanoma cells. We then
      utilized this ST-expressing tumor cell line to test the efficacy of a DNA vaccine
      encoding ST. In ST-expressing tumor-bearing mice, this vaccine, pcDNA3-MCC/ST,
      generated a significant number of ST antigenic peptide-specific CD8+ T cells and
      experienced markedly enhanced survival compared to mice vaccinated with empty
      vector. CONCLUSIONS: The formation of an effective vaccine against MCPyV has the
      potential to advance the field of MCC therapy and may contribute to the control
      of this severe malignancy through immunotherapy. Both of the innovative
      technologies presented here provide opportunities to develop and test MCPyV
      targeted therapies for the control of Merkel cell carcinoma.

PMID- 23856460
TI  - Effect of an investigational CYP17A1 inhibitor, orteronel (TAK-700), on estrogen-
      and corticoid-synthesis pathways in hypophysectomized female rats and on the
      serum estradiol levels in female cynomolgus monkeys.
AB  - Orteronel (TAK-700) is an investigational, non-steroidal inhibitor of CYP17A1
      with preferential inhibition of 17,20-lyase in NCI-H295 cells. Estrogen is
      synthesized from androgen by aromatase activity, and the effect of orteronel on
      estrogen synthesis was therefore evaluated. First, it was confirmed that
      orteronel does not directly inhibit aromatase activity. Second, the specific
      decline of serum estradiol and androgen levels in hypophysectomized female rats
      by orteronel in comparison with aromatase inhibitor anastrozole was evaluated;
      orteronel at doses >=3mg/kg significantly suppressed serum estradiol,
      testosterone, androstenedione and 17-hydroxyprogesterone levels, and increased
      progesterone levels in the estrogen-synthesis pathway. Orteronel, at a dose of
      300mg/kg, suppressed serum estradiol concentrations to a similar degree as
      0.1mg/kg anastrozole. In contrast, in the corticoid-synthesis pathway, serum
      aldosterone, corticosterone, and progesterone levels did not change significantly
      following administration of 300mg/kg of orteronel. Third, the effect of multiple
      oral administration of orteronel on serum estradiol levels in regularly cycling
      female cynomolgus monkeys was evaluated. Orteronel at 15mg/kg/day
      (7.5mg/kg/treatment, twice daily [bid]) continued to suppress the estradiol surge
      prior to the start of luteal phase for 1.5-times the average duration of three
      consecutive, pre-treatment menstrual cycles, while serum progesterone was
      maintained at levels almost equal to those in the luteal phase although a certain
      portion of this increased level of progesterone could be of adrenal-origin. This
      suppressive effect on estradiol surge was thought to be reversible since serum
      estradiol levels started to rise immediately after the discontinuation of
      orteronel. Estradiol surge was not abrogated by treatment with anastrozole
      0.2mg/kg/day (0.1mg/kg/treatment, bid). In summary, orteronel can suppress serum
      estradiol concentrations in hypophysectomized female rats and monkeys through
      selective inhibition of CYP17A1 activity, suggesting that orteronel might be
      effective for hormone-dependent breast cancers and estrogen-dependent diseases. 

PMID- 23856462
TI  - Michaelis and Menten and the long road to the discovery of cooperativity.
AB  - This article sketches the road from the establishment of the principles of enzyme
      kinetics, at the beginning of the 20th century, to the discovery of regulatory
      mechanisms and the models to explain them, from the middle of the century
      onwards. A long gap in time separates the two periods, in which technological
      advances were made that allowed the discovery of feedback inhibition and
      cooperativity. In particular, these discoveries and the theory needed to explain
      them could not have been made without knowledge of the major metabolic pathways
      and the enzymes and metabolites involved in them. 

PMID- 23856461
TI  - A new regulatory principle for in vivo biochemistry: pleiotropic low affinity
      regulation by the adenine nucleotides--illustrated for the glycolytic enzymes of
      Saccharomyces cerevisiae.
AB  - Enzymology tends to focus on highly specific effects of substrates, allosteric
      modifiers, and products occurring at low concentrations, because these are most
      informative about the enzyme's catalytic mechanism. We hypothesized that at
      relatively high in vivo concentrations, important molecular monitors of the state
      of living cells, such as ATP, affect multiple enzymes of the former and that
      these interactions have gone unnoticed in enzymology. We test this hypothesis in
      terms of the effect that ATP, ADP, and AMP might have on the major free-energy
      delivering pathway of the yeast Saccharomyces cerevisiae. Assaying cell-free
      extracts, we collected a comprehensive set of quantitative kinetic data
      concerning the enzymes of the glycolytic and the ethanol fermentation pathways.
      We determined systematically the extent to which the enzyme activities depend on
      the concentrations of the adenine nucleotides. We found that the effects of the
      adenine nucleotides on enzymes catalysing reactions in which they are not
      directly involved as substrate or product, are substantial. This includes effects
      on the Michaelis-Menten constants, adding new perspective on these, 100 years
      after their introduction.

PMID- 23856463
TI  - A link between two tumorigenic proteins, CD44 and p21WAF1: CD44 increases phorbol
      ester-induced expression of p21WAF1 by stabilizing its mRNA and extending protein
      half-life.
AB  - The cell surface glycoprotein CD44 enhances phorbol-12-myristate 13-acetate (TPA)
      induced expression of p21WAF1 by stabilizing its mRNA and enhancing the protein's
      half-life in several cell lines. Only the plasma membrane-anchored cytoplasmic
      tail of CD44 and its interacting ezrin, radixin, moesin (ERM) proteins are
      required for this effect. A mitogen activated kinase (MEK) inhibitor abolishes
      the action of CD44 on p21. Down-regulation of p21 dramatically decreased
      anchorage-independence of a cancer cell line, whereas CD44 expression in this
      background could partially rescue the phenotype.

PMID- 23856464
TI  - The effect of insecticides on the non-target predatory mite Kampimodromus
      aberrans: laboratory studies.
AB  - The side-effects of pesticides on predatory mites have been investigated at
      various levels and international teams (e.g., the IOBC/wprs Working Group
      "Pesticides and beneficial organisms") have selected a few species of predatory
      mites occurring in Central and Northern Europe as representative for such
      studies. Key biocontrol species occurring in Southern Europe have received much
      less attention. Kampimodromus aberrans is the most important predator of
      herbivorous mites in South-European vineyards treated with selective pesticides.
      The impact of pesticides on K. aberrans populations has been studied in field
      conditions whereas few toxicological tests have been conducted in the laboratory
      because of difficulties in rearing this species. A method for rearing K. aberrans
      in the laboratory has recently been set up allowing toxicological studies to be
      conducted. In this paper, a toxicological method to assess the effects of
      pesticides on K. aberrans is described and the effects of insecticides frequently
      used in European vineyards on two K. aberrans strains are reported. These strains
      were collected from vineyards treated with organophosphates. Insecticides
      characterized by different modes of action were selected for trials. Among these,
      etofenprox and spinosad were classified as harmful to predatory mites.
      Chlorpyrifos reduced predatory mite fecundity, and was classified as moderately
      harmful for both strains. The toxicity of thiamethoxam and flufenoxuron varied
      with the strain (low to moderate). Indoxacarb and methoxyfenozide appeared to be
      harmless or slightly harmful. Implications of this study for adopting IPM tactics
      with a reduced risk for K. aberrans are discussed. 

PMID- 23856465
TI  - Risk and toxicity assessments of heavy metals in sediments and fishes from the
      Yangtze River and Taihu Lake, China.
AB  - Heavy metal pollution is one of the most serous environmental issues globally. To
      evaluate the metal pollution in Jiangsu Province of China, the total
      concentrations of heavy metals in sediments and fishes from the Yangtze River and
      Taihu Lake were analyzed. Ecological risk of sediments and human health risk of
      fish consumption were assessed respectively. Furthermore, toxicity of samples on
      expression of the stress responsive genes was evaluated using microbial live cell
      array method. The results showed that the heavy metals concentrations in
      sediments from the Yangtze River were much higher than those in sediments from
      the Taihu Lake. However, the fishes from the Taihu Lake had higher concentrations
      of heavy metals than fishes from the Yangtze River. Ecological risk evaluation
      showed that the heavy metal contaminants in sediments from the Yangtze River
      posed higher risk of adverse ecological effects, while sediments from the study
      areas of Taihu Lake were relatively safe. Health risk assessment suggested that
      the heavy metals in fishes of both Yangtze River and Taihu Lake might have risk
      of adverse health effects to human. The toxicity assessment indicated that the
      heavy metals in these sediments and fishes showed transcriptional effects on the
      selected 21 stress responsive genes, which were involved in the pathways of DNA
      damage response, chemical stress, and perturbations of electron transport.
      Together, this field investigation combined with chemical analysis, risk
      assessment and toxicity bioassay would provide useful information on the heavy
      metal pollution in Jiangsu Province. 

PMID- 23856466
TI  - Elemental and spectroscopic characterization of fractions of an acidic extract of
      oil sands process water.
AB  - 'Naphthenic acids' (NAs) in petroleum produced water and oil sands process water
      (OSPW), have been implicated in toxicological effects. However, many are not well
      characterized. A method for fractionation of NAs of an OSPW was used herein and a
      multi-method characterization of the fractions conducted. The unfractionated OSPW
      acidic extract was characterized by elemental analysis, electrospray ionization
      Orbitrap-mass spectrometry (ESI-MS), and an esterified extract by Fourier
      Transform infrared (FTIR) and ultraviolet-visible (UV) absorption spectroscopy
      and by comprehensive multidimensional gas chromatography-MS (GCxGC-MS). Methyl
      esters were fractionated by argentation solid phase extraction (Ag(+) SPE) and
      fractions eluting with: hexane; diethyl ether: hexane and diethyl ether,
      examined. Each was weighed, examined by elemental analysis, FTIR, UV, GC-MS and
      GCxGC-MS (both nominal and high resolution MS). The ether fraction, containing
      sulfur, was also examined by GCxGC-sulfur chemiluminescence detection (GCxGC
      SCD). The major ions detected by ESI-MS in the OSPW extract were assigned to
      alicyclic and aromatic 'O2' acids; sulfur was also present. Components recovered
      by Ag(+) SPE were also methyl esters of alicyclic and aromatic acids; these
      contained little sulfur or nitrogen. FTIR spectra showed that hydroxy acids and
      sulfoxides were absent or minor. UV spectra, along with the C/H ratio, further
      confirmed the aromaticity of the hexane:ether eluate. The more minor ether eluate
      contained further aromatics and 1.5% sulfur. FTIR spectra indicated free
      carboxylic acids, in addition to esters. Four major sulfur compounds were
      detected by GCxGC-SCD. GCxGC-high resolution MS indicated these were methyl
      esters of C18 S-containing, diaromatics with >=C3 carboxylic acid side chains.

PMID- 23856467
TI  - Polybrominated diphenyl ethers and polychlorinated biphenyls in cord blood from
      women in Poland.
AB  - The purpose of this study was to assess human exposure in the prenatal period to
      selected PBDEs (BDE-47, BDE-99, BDE-153) and PCBs (CB-77, CB-101, CB-118, CB-126,
      CB-138, CB-153, CB-170, CB-180) basing on the analysis of these compounds in cord
      blood. The experimental material consisted of 89 cord blood samples taken from
      women resident in Warsaw and its vicinity. In over 90% of all tested samples the
      presence of congeners CB-153, CB-138, CB-180 and BDE-47 was identified. The least
      frequently found were CB-126 and BDE-153, which were present at relatively low
      concentration levels. Among all analysed PCBs, the highest average concentrations
      were found in the case of congeners CB-138 (11.8 ng/g of fat) and CB-153 (43.4
      ng/g of fat), whereas the lowest was in the case of CB-170 (0.4 ng/g of fat) and
      CB-126 (0.1 ng/g of fat). In the case of PBDEs the greatest share in the total
      concentration was that of the congeners BDE-47 and BDE-99, whereas the smallest
      share was that of the higher brominated congener BDE-153. These results suggest
      that human exposure to the examined compounds begins already in the period of
      intrauterine life. The comparison of our own results with the findings of other
      authors indicates that the PCBs and PBDEs levels in cord blood of women living in
      Poland do not differ from the respective concentrations in cord blood of other
      female inhabitants of Europe.

PMID- 23856468
TI  - Imposex development in Hexaplex trunculus (Gastropoda: Caenogastropoda) involves
      changes in the transcription levels of the retinoid X receptor (RXR).
AB  - In order to further demonstrate that TBT-induced imposex through RXR signaling is
      not species-specific, Hexaplex trunculus was selected as an experimental model
      species. We first isolated RXR in H. trunculus, and determined gene transcription
      through quantitative real-time PCR in key tissues (e.g., penis/penis-forming area
      and central nervous system:- CNS), upon exposure to tributyltin (TBT) (5 and 50
      ng TBTL(-1)). Two months of exposure to TBT induced imposex and led to a
      significant increase in the severity of the phenomenon in females and an increase
      in male penis lengths. Exposure to TBT altered RXR gene transcription in a tissue
      and sex-specific manner. In the CNS, there were no significant changes in RXR
      gene transcription between control and TBT-exposed females. A similar trend was
      observed in male CNS. On the contrary, in the penis-forming area/penis of females
      exposed to TBT, a significant increase in RXR gene transcription was observed in
      the 50 ng TBTL(-1) group. Furthermore, a positive correlation was observed
      between overall female penis lengths and RXR gene transcription. In males,
      although a trend towards an increase in RXR gene transcription in penis was
      observed, differences did not reach significance. Overall, the results of the
      present study give further support to a local role of RXR in the penis-forming
      area during the development of imposex by TBT, thus suggesting a conserved
      function of RXR in penis formation at least within prosobranch gastropods.

PMID- 23856469
TI  - Organochlorine compounds, nitro musks and perfluorinated substances in breast
      milk - results from Bavarian Monitoring of Breast Milk 2007/8.
AB  - The aim of the Bavarian Monitoring of Breast Milk (BAMBI) project was to examine
      10 organochlorine pesticides (OPs), 3 nitro musks, 6 indicator polychlorinated
      biphenyls (PCBs), 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated
      dibenzofurans (PCDFs), 12 dioxin-like PCBs (dl-PCBs) and several perfluorinated
      alkyl compounds in breast milk samples. A total of 516 breast milk samples were
      collected from seven regions in Bavaria and were analyzed by means of GC/ECD,
      GC/HRMS, and LC/MS-MS. Concerning the OPs, only hexachlorobenzene and a
      metabolite of DDT, 1,1-dichloro-2,2-bis(4-chlorophenyl) ethylene (p,p'-DDE),
      could be quantified in all samples (median: 16 ngg(-1) lipid and 63 ngg(-1)
      lipid, respectively). Median concentrations of 150 ngg(-1) lipid (range: 3-1900
      ngg(-1) lipid) were found for the sum of the indicator PCBs. The concentrations
      of the PCDDs/PCDFs and the dl-PCBs ranged from 0.8 to 15.1 (median 5.7) pg WHO
      TEQ1998g(-1) lipid and from 1.5 to 18.9 pg (median 6.4) WHO-TEQ1998 g(-1) lipid,
      respectively. The median perfluorooctane sulfonate concentration was 0.05 MUgL(
      1) (range: <0.02-0.26 MUgL), while the other PFCs were observed only in a subset
      of samples. On the basis of the median and 95th percentile concentration,
      "medium" and "high" intake levels were estimated for a 3-month-old exclusively
      breastfed infant. In particular, "medium" and "high" intake levels were
      calculated of 69 and 133 pg WHO1998 TEQ kg(-1) b.w. for PCDDs/PCDFs, 8 and 21
      ngkg(-1) b.w. for dl-PCBs, and 6 and 25 ngkg(-1) b.w. for perfluorooctane
      sulfonate, respectively. The calculated intake for perfluorinated substances is
      clearly below the tolerable daily intake (TDI), while the established TDI values
      are still clearly exceeded for PCDDs/PCDFs and dl-PCBs.

PMID- 23856470
TI  - Evaluation of phenanthrene toxicity on earthworm (Eisenia fetida): an
      ecotoxicoproteomics approach.
AB  - The goal of this study was to identify promising new biomarkers of phenanthrene
      by identifying differentially expressed proteins in Eisenia fetida after exposure
      to phenanthrene. Extracts of earthworm epithelium collected at days 2, 7, 14, and
      28 after phenanthrene exposure were analyzed by two dimensional electrophoresis
      (2-DE) and quantitative image analysis. Comparing the intensity of protein spots,
      36 upregulated proteins and 45 downregulated proteins were found. Some of the
      downregulated and upregulated proteins were verified by MALDI-TOF/TOF-MS and
      database searching. Downregulated proteins in response to phenanthrene exposure
      were involved in glycolysis, energy metabolism, chaperones, proteolysis, protein
      folding and electron transport. In contrast, oxidation reduction, oxygen
      transport, defense systems response to pollutant, protein biosynthesis and fatty
      acid biosynthesis were upregulated in phenanthrene-treated E. fetida. In
      addition, ATP synthase b subunit, lysenin-related protein 2, lombricine kinase,
      glyceraldehyde 3-phosphate dehydrogenase, actinbinding protein, and extracellular
      globin-4 seem to be potential biomarkers since these biomarker were able to low
      levels (2.5 mg kg(-1)) of phenanthrene. Our study provides a functional profile
      of the phenanthrene-responsive proteins in earthworms. The variable levels and
      trends in these spots could play a potential role as novel biomarkers for
      monitoring the levels of phenanthrene contamination in soil ecosystems.

PMID- 23856472
TI  - Population analyses of Amblyomma maculatum ticks and Rickettsia parkeri using
      single-strand conformation polymorphism.
AB  - Gulf Coast ticks, Amblyomma maculatum, and the zoonotic agents they transmit,
      Rickettsia parkeri, are expanding into areas in the United States where they were
      not previously reported, and are emerging threats for public and veterinary
      health. The dynamics of this tick-pathogen system and implications for disease
      transmission are still unclear. To assess genetic variation of tick and
      rickettsial populations, we collected adult A. maculatum from 10 sites in
      Mississippi, 4 in the northern, one in the central, and 5 in the southern part of
      the state. PCR amplicons from tick mitochondrial 16S rRNA and rickettsial ompA
      genes as well as 5 intergenic spacer regions were evaluated for genetic variation
      using single-strand conformation polymorphism analysis. Frequencies of the 4 tick
      16S haplotypes were not significantly different among regions of Mississippi, but
      within sites there were differences in distribution that can be explained by high
      migration rates. Phylogenetically, one lineage of tick haplotypes was a species
      poor sister group to remaining haplotypes in the species-rich sister group. No
      genetic variation was identified in any of the 6 selected gene targets of R.
      parkeri examined in the infected ticks, suggesting high levels of intermixing. 

PMID- 23856471
TI  - Identification of a KCNQ1 polymorphism acting as a protective modifier against
      arrhythmic risk in long-QT syndrome.
AB  - BACKGROUND: Long-QT syndrome (LQTS) is characterized by such striking clinical
      heterogeneity that, even among family members carrying the same mutation,
      clinical outcome can range between sudden death and no symptoms. We investigated
      the role of genetic variants as modifiers of risk for cardiac events in patients
      with LQTS. METHODS AND RESULTS: In a matched case-control study including 112
      patient duos with LQTS from France, Italy, and Japan, 25 polymorphisms were
      genotyped based on either their association with QTc duration in healthy
      populations or on their role in adrenergic responses. The duos were composed of 2
      relatives harboring the same heterozygous KCNQ1 or KCNH2 mutation: 1 with cardiac
      events and 1 asymptomatic and untreated. The findings were then validated in 2
      independent founder populations totaling 174 symptomatic and 162 asymptomatic
      patients with LQTS, and a meta-analysis was performed. The KCNQ1 rs2074238 T
      allele was significantly associated with a decreased risk of symptoms 0.34 (0.19
      0.61; P<0.0002) and with shorter QTc (P<0.0001) in the combined discovery and
      replication cohorts. CONCLUSIONS: We provide evidence that the KCNQ1 rs2074238
      polymorphism is an independent risk modifier with the minor T-allele conferring
      protection against cardiac events in patients with LQTS. This finding is a step
      toward a novel approach for risk stratification in patients with LQTS.

PMID- 23856475
TI  - Why randomized interventional studies.
AB  - A number of arguments have shown that randomization is not essential in
      experimental design. Scientific conclusions can be drawn on data from
      experimental designs that do not involve randomization. John Worrall has recently
      taken proponents of randomized studies to task for suggesting otherwise. In doing
      so, however, Worrall makes an additional claim: randomized interventional studies
      are epistemologically equivalent to observational studies, providing the
      experimental groups are comparable according to background knowledge. I argue
      against this claim. In the context of testing the efficacy of drug therapies,
      well-designed interventional studies are epistemologically superior to well
      designed observational studies because they have the capacity to avoid a type of
      selection bias. Although arguments for interventional studies are present in the
      medical literature, these arguments are too often presented as an argument for
      randomization. Randomization in interventional studies is defended on Bayesian
      grounds. 

PMID- 23856473
TI  - Identification of tick-borne encephalitis virus in ticks collected in
      southeastern Hungary.
AB  - Tick-borne encephalitis virus (TBEV) is an arthropod-borne viral pathogen causing
      infections in Europe and is responsible for most arbovirus central nervous system
      infections in Hungary. Assessing the TBEV prevalence in ticks through detection
      of genomic RNA is a broadly accepted approach to estimate the transmission risk
      from a tick bite. For this purpose, 2731 ticks were collected from the
      neighboring area of the town of Devavanya, located in southeastern Hungary, which
      is considered a low-risk-transmission area for TBEV. Altogether, 2300 ticks were
      collected from the vegetation, while 431 were collected from rodents. Samples
      were pooled and then screened for TBEV with a newly designed semi-nested RT-PCR
      (RT-snPCR) targeting the NS1 genomic region. PCR results were confirmed by direct
      sequencing of the second round amplicons. Among the 3 different collected tick
      species (Ixodes ricinus, Haemaphysalis concinna, Dermacentor marginatus), I.
      ricinus was the only species that tested positive for TBEV. TBEV-positive ticks
      were collected from small mammals or from the vegetation. One nymphal pool and 4
      larval pools tested positive for TBEV. The only positive nymphal pool was unfed
      and came from vegetation, while ticks of the 4 positive larval pools were
      collected from rodents. Minimal TBEV prevalence in ticks was 0.08% for unfed
      nymphs and 0.78% for feeding larvae. Our results indicate that further long-term
      investigations on the occurrence of TBEV are needed to better describe the
      geographic distribution and the prevalence of infected ticks in Hungary. 

PMID- 23856476
TI  - The limits of social justice as an aspect of medical professionalism.
AB  - Contemporary accounts of medical ethics and professionalism emphasize the
      importance of social justice as an ideal for physicians. This ideal is often
      specified as a commitment to attaining the universal availability of some level
      of health care, if not of other elements of a "decent minimum" standard of
      living. I observe that physicians, in general, have not accepted the importance
      of social justice for professional ethics, and I further argue that social
      justice does not belong among professional norms. Social justice is a norm of
      civic rather than professional life; professional groups may demand that their
      members conform to the requirements of citizenship but ought not to require civic
      virtues such as social justice. Nor should any such requirements foreclose
      reasonable disagreement as to the content of civic norms, as requiring adherence
      to common specifications of social justice would do. Demands for any given form
      of social justice among physicians are unlikely to bear fruit as medical
      education is powerless to produce this virtue. 

PMID- 23856477
TI  - Real and alleged problems for Daniels's account of health justice.
AB  - Norman Daniels's theory of health justice is the most comprehensive and
      systematic such theory we have. In one of the few articles published so far on
      Daniels's new book, Just Health, Benjamin Sachs argues that Daniels's core
      "principle of equality of opportunity does not do the work Daniels needs it to
      do." Yet Sachs's objections to Daniels's framework are deeply flawed. Where these
      arguments do not rely on significant misreadings of Daniels, they ignore sensible
      strands in Just Health that considerably dull their force. After disarming
      Sachs's arguments against Daniels's theory, I explain why I agree with Sachs's
      conclusion: Daniels's equality of opportunity-based account of health justice
      rests on shaky foundations. 

PMID- 23856478
TI  - Procreative altruism: beyond individualism in reproductive selection.
AB  - Existing debate on procreative selection focuses on the well-being of the future
      child. However, selection decisions can also have significant effects on the well
      being of others. Moreover, these effects may run in opposing directions; some
      traits conducive to the well-being of the selected child may be harmful to
      others, whereas other traits that limit the child's well-being may preserve or
      increase that of others. Prominent selection principles defended to date instruct
      parents to select a child, of the possible children they could have, likely to
      have a good (or nonbad) life, but they do not instruct parents to independently
      take the well-being of others into account. We refer to these principles as
      individualistic selection principles. We propose a new selection principle
      Procreative Altruism-according to which parents have significant moral reason to
      select a child whose existence can be expected to contribute more to (or detract
      less from) the well-being of others than any alternative child they could have.
      We present the case for adopting Procreative Altruism alongside any of the major
      individualistic selection principles proposed to date and defend this two
      principle model against a range of objections. 

PMID- 23856479
TI  - How the contractualist account of preconception negligence undermines prenatal
      reproductive autonomy.
AB  - Suppose a physician advises a woman to delay her planned pregnancy for a few
      months in order to significantly reduce the likelihood that her baby will suffer
      with Spina Bifida. If the woman chooses to ignore this advice and conceives soon
      after, I believe most people would consider it a matter of common sense that the
      child thus born is a victim of this woman's negligence, even if it is fortunate
      enough to not be burdened with Spina Bifida. This common sense judgement appeared
      to have been done in by the fact that the timing of conception can be identity
      influencing, and so the child that is born only exists because of its mother's
      decision to ignore her physician's advice. However, recently, contemporary
      contractualist theories have been used to make sense of preconception negligence
      towards persons whose existence is a result of that same negligence. I will
      briefly discuss this interesting development and then show how this retrieval of
      the common sense judgement comes at a great cost to prenatal reproductive
      autonomy. 

PMID- 23856480
TI  - The dead donor rule: a defense.
AB  - Miller, Truog, and Brock have recently argued that the "dead donor rule," the
      requirement that donors be determined to be dead before vital organs are procured
      for transplantation, cannot withstand ethical scrutiny. In their view, the dead
      donor rule is inconsistent with existing life-saving practices of organ
      transplantation, lacks a cogent ethical rationale, and is not necessary for
      maintenance of public trust in organ transplantation. In this paper, the second
      of these claims will be evaluated. (The first and third are not addressed.) The
      claim that the dead donor rule lacks a cogent ethical rationale will be shown to
      be an expression of the contemporary rejection of the moral significance of the
      traditional distinction between killing and allowing to die. The moral
      significance of this traditional distinction, and the associated norm that
      doctors should not kill their patients, will be defended, and this critique of it
      shown to be unsuccessful. 

PMID- 23856481
TI  - The social model of disability: dichotomy between impairment and disability.
AB  - The rhetoric of the social model of disability is presented, and its basic claims
      are critiqued. Proponents of the social model use the distinction between
      impairment and disability to reduce disabilities to a single social dimension
      social oppression. They downplay the role of biological and mental conditions in
      the lives of disabled people. Consequences of denying biological and mental
      realities involving disabilities are discussed. People will benefit most by
      recognizing both the biological and the social dimensions of disabilities. 

PMID- 23856486
TI  - Control of ventilation in COPD and lung injury.
AB  - Breathing occurs in single breaths and in patterns which are altered by the
      onset, progression and resolution of respiratory diseases. Through modulations of
      rate, depth, and patterning of breathing, the ventilatory control system
      maintains numerous critical variables within their homeostatic ranges. A dynamic
      respiratory control system is critical to successful adaptation in the face of
      progressive pulmonary pathology. The objective of this review, is to illustrate
      functional changes and compensatory mechanisms which occur with the onset and
      progression of acute and chronic lung disease. Chronic obstructive pulmonary
      disease (COPD) will be considered as a model of a slowly progressive pulmonary
      process, where destruction of lung parenchyma and airway obstruction leads to
      hypoxemia and hypercapnia. Over time, adaptations of the respiratory control
      system to this disease include changes in the intrinsic properties of respiratory
      muscles, chemoreceptor signaling, and central respiratory drive which increase
      motor output to the respiratory muscles. In contrast, acute respiratory distress
      syndrome (ARDS) is an exemplar of an acute pulmonary process. The result of
      severe lung injury, ARDS is characterized by lung infiltrates, rapidly
      progressive hypoxemic respiratory failure, and possible progression to pulmonary
      fibrosis. Changes in breathing patterns result from these functional changes, as
      well as altered processing of afferent feedback by the central controller,
      possibly influenced by brainstem inflammation. Taken together, these disease
      models highlight the plasticity of the respiratory control system in response to
      the development and progression of lung disease. 

PMID- 23856487
TI  - Hypoxia and metastasis in an orthotopic cervix cancer xenograft model.
AB  - BACKGROUND: Hypoxia can promote tumor metastasis by mechanisms that are believed
      to result from changes in gene expression. The current study examined the role of
      putative metastatic genes regulated by cyclic hypoxia in relation to metastasis
      formation in orthotopic models of cervix cancer. METHODS: Orthotopic tumors
      derived from ME180 human cervix cancer cells or from early generation human
      cervix cancer xenografts were exposed to cyclic hypoxic conditions during growth
      in vivo and tumor growth and lymphnode metastases were monitored. Expression of
      the chemokine receptor CXCR4 and various genes in the Hedgehog (Hh) pathway were
      inhibited using genetic (inducible shRNA vs CXCR4) small molecule (AMD3100) or
      antibody (5E1) treatment (CXCR4 and Hh genes, respectively) during tumor growth.
      RESULTS: As reported previously, exposure of tumor bearing mice to cyclic hypoxia
      caused a reduction of tumor growth but a large increase in metastasis. Inhibition
      of CXCR4 or Hh gene activity during tumor growth further reduced primary tumor
      size and reduced lymphatic metastasis to levels below those seen in control mice
      exposed to normoxic conditions. CONCLUSION: Blocking CXCR4 or Hh gene expression
      are potential therapeutic pathways for improving cervix cancer treatment.

PMID- 23856488
TI  - Childhood blood pressure: trends and future tracks.

PMID- 23856489
TI  - Novel role of NOD2 in mediating Ca2+ signaling: evidence from NOD2-regulated
      podocyte TRPC6 channels in hyperhomocysteinemia.
AB  - Although hyperhomocysteinemia (hHcys) has been recognized as an important
      independent risk factor in the progression of end-stage renal disease and in the
      development of cardiovascular complications related to end-stage renal disease,
      the mechanisms triggering the pathogenic actions of hHcys are not yet fully
      understood. The present study was designed to investigate the contribution of
      nucleotide-binding oligomerization domain containing 2 (NOD2), an intracellular
      innate immunity mediator, to the development of glomerulosclerosis in hHcys. Our
      results showed that NOD2 deficiency ameliorated renal injury in mice with hHcys.
      We further discovered the novel role of NOD2 in mediating Ca(2+) signaling and
      found that homocysteine-induced NOD2 expression enhanced transient receptor
      potential cation channel 6 (TRPC6) expression and TRPC6-mediated calcium influx
      and currents, leading to intracellular Ca(2+) release, ultimately resulting in
      podocyte cytoskeleton rearrangement and apoptosis. Moreover, we found that
      nephrin expression was downregulated dependently by NOD2, and overexpression of
      nephrin attenuated homocysteine-induced TRPC6 expression in podocytes. The
      results add evidence to support the essential role of nephrin in mediating NOD2
      induced TRPC6 expression in hHcys. In conclusion, our results for the first time
      establish a previously unknown function of NOD2 for the regulation of TRPC6
      channels, suggesting that TRPC6-dependent Ca(2+) signaling is one of the critical
      signal transduction pathways that links innate immunity mediator NOD2 to podocyte
      injury. Pharmacological targeting of NOD2 signaling pathways at multiple levels
      may help design a new approach to develop therapeutic strategies for treatment of
      hHcys-associated end-stage renal disease. 

PMID- 23856490
TI  - Angiotensin-(1-7) and kidney disease: friend or foe.

PMID- 23856491
TI  - Stimulation of aldosterone synthesis by angiotensin II in the brain: support for
      positive feedback in hypertension?

PMID- 23856492
TI  - Childhood blood pressure trends and risk factors for high blood pressure: the
      NHANES experience 1988-2008.
AB  - The obesity epidemic in children makes it plausible that prevalence rates of
      elevated blood pressure (BP) are increasing over time. Yet, previous literature
      is inconsistent because of small sample sizes. Also, it is unclear whether
      adjusting for risk factors can explain longitudinal trends in prevalence of
      elevated BP. Thus, we analyzed a population-based sample of 3248 children in
      National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and
      8388 children in continuous NHANES (1999-2008), aged 8 to 17 years. Our main
      outcome measure was elevated BP (systolic BP or diastolic BP >= 90th percentile
      or systolic BP/diastolic BP >= 120/80 mm Hg). We found that the prevalence of
      elevated BP increased from NHANES III to NHANES 1999-2008 (Boys: 15.8% to 19.2%,
      P=0.057; Girls: 8.2% to 12.6%, P=0.007). Body mass index (Q4 versus Q1; odds
      ratio=2.00; P<0.001), waist circumference (Q4 versus Q1; odds ratio=2.14;
      P<0.001), and sodium (Na) intake (>= 3450 mg versus <2300 mg/2000 calories; odds
      ratio=1.36; P=0.024) were independently associated with prevalence of elevated
      BP. Also, mean systolic BP, but not diastolic BP, was associated with increased
      Na intake in children (quintile 5 [Q5] versus quintile 1 [Q1] of Na intake;
      beta=1.25 +/- 0.58; P=0.034). In conclusion, we demonstrate an association
      between high Na intake and elevated BP in children. After adjustment for age,
      sex, race/ethnicity, body mass index, waist circumference, and sodium intake,
      odds ratio for elevated BP in NHANES 1999-2008 versus NHANES III=1.27, P=0.069.

PMID- 23856493
TI  - Role of brain corticosterone and aldosterone in central angiotensin II-induced
      hypertension.
AB  - Circulating angiotensin II (Ang II) activates a central aldosterone
      mineralocorticoid receptor neuromodulatory pathway, which mediates most of the
      Ang II-induced hypertension. This study examined whether specific central
      infusion of Ang II also activates this central aldosterone-mineralocorticoid
      receptor pathway. Intracerebroventricular infusion of Ang II at 1.0, 2.5, and
      12.5 ng/min for 2 weeks caused dose-related increases in water intake, Ang II
      concentration in the cerebrospinal fluid, and blood pressure.
      Intracerebroventricular Ang II, at 2.5 and 12.5 ng/min, increased hypothalamic
      aldosterone and corticosterone, as well as plasma aldosterone and corticosterone
      without affecting plasma Ang II levels. Intracerebroventricular infusion of the
      aldosterone synthase inhibitor FAD286-but not the mineralocorticoid receptor
      blocker eplerenone-inhibited by ~60% the Ang II-induced increase in hypothalamic
      aldosterone. Both blockers attenuated by ~50% the increase in plasma aldosterone
      and corticosterone with only minimal effects on hypothalamic corticosterone. By
      telemetry, intracerebroventricular infusion of Ang II maximally increased blood
      pressure within the first day with no further increase over the next 2 weeks.
      Intracerebroventricular infusion of FAD286 or eplerenone did not affect the
      initial pressor responses but similarly prevented 60% to 70% of the chronic
      pressor responses to intracerebroventricular infusion of Ang II. These results
      indicate distinctly different patterns of blood pressure increase by circulating
      versus central Ang II and support the involvement of a brain aldosterone
      mineralocorticoid receptor-activated neuromodulatory pathway in the chronic
      hypertension caused by both circulating and central Ang II. 

PMID- 23856495
TI  - Optimization of mead production using response surface methodology.
AB  - The main aim of the present work was to optimize mead production using Response
      Surface Methodology. The effects of temperature (x1: 20-30 degrees C) and
      nutrients concentration (x2: 60-120g /hL) on mead quality, concerning the final
      concentrations of glucose (Y1), fructose (Y2), ethanol (Y3), glycerol (Y4) and
      acetic acid (Y5), were studied. Twelve operational conditions were tested. No
      delays and moods were observed during fermentations. The second order polynomial
      models determined produced satisfactory fittings of the experimental data with
      regard to glucose (R2=0.646, p=0.001), ethanol (R2=0.741, p=0.049), glycerol
      (R2=0.899, p=0.002), fructose (R2=0.902, p=0.033) and acetic acid (R2=0.913,
      p=0.001). The optimum extraction conditions determined in order to maximize the
      combined responses were 24 degrees C and a nutrients concentration of 0.88g/L.
      The mead produced under these conditions had the following characteristics:
      ethanol concentration of 10.2%, acetic acid 0.54 g/L, glycerol 7.8 g/L, glucose
      1.8 g/L and fructose 2.5 g/L. These values were in agreement with the predicted
      and were within the safe limit established for acetic acid and the recommended
      range for glycerol. Furthermore, the residual sugars concentration was also low,
      decreasing the possibility of occurring undesirable refermentations.

PMID- 23856494
TI  - Glutathione defense mechanism in liver injury: insights from animal models.
AB  - Glutathione (GSH) is the most abundant cellular thiol antioxidant and it exhibits
      numerous and versatile functions. Disturbances in GSH homeostasis have been
      associated with liver diseases induced by drugs, alcohol, diet and environmental
      pollutants. Until recently, our laboratories and others have developed mouse
      models with genetic deficiencies in glutamate-cysteine ligase (GCL), the rate
      limiting enzyme in the GSH biosynthetic pathway. This review focuses on
      regulation of GSH homeostasis and, specifically, recent studies that have
      utilized such GSH-deficient mouse models to investigate the role of GSH in liver
      disease processes. These studies have revealed a differential hepatic response to
      distinct profiles of hepatic cellular GSH concentration. In particular, mice
      engineered to not express the catalytic subunit of GCL in hepatocytes [Gclc(h/h)
      mice] experience almostcomplete loss of hepatic GSH (to 5% of normal) and develop
      spontaneous liver pathologies characteristic of various clinical stages of liver
      injury. In contrast, mice globally engineered to not express the modifier subunit
      of GCL [Gclm-/- mice] show a less severe hepatic GSH deficit (to ~15% of normal)
      and exhibit overall protection against liver injuries induced by a variety of
      hepatic insults. Collectively, these transgenic mouse models provide interesting
      new insights regarding pathophysiological functions of GSH in the liver.

PMID- 23856496
TI  - Can garlic oil ameliorate diabetes-induced oxidative stress in a rat liver model?
      A correlated histological and biochemical study.
AB  - This study aimed to characterise the structural changes in liver of an alloxan
      induced diabetic rat and to explain such changes in terms of the biochemical
      changes in free radicals and antioxidants. In addition, it aimed to determine the
      potential ability of garlic oil to alter these changes. The study groups were:
      control (n=12), alloxan-induced diabetic rats (n=10) and alloxan-induced diabetic
      rats treated with garlic oil (10 mg/kg body weight (n=10)). Markers of oxidative
      stress were assessed. Small pieces of the liver were processed for transmission
      electron microscopic study. Garlic oil caused a significant decrease in levels of
      LPO in plasma (0.26 vs 0.53), erythrocyte lysate (14.4 vs 24.8) and liver tissue
      homogenate (1.04 vs 2.08), whereas those of thiols were significantly elevated
      (1.2 vs 0.46), (24 vs 15) in plasma and erythrocyte lysate respectively. SOD
      activity and G-S-T activity were significantly elevated in erythrocyte lysate
      (5.7 vs 3.3) (377 vs 179) and liver homogenate (1.4 vs 0.5) (752 vs 623)
      respectively after garlic oil administration. Ultrastructural study of the liver
      confirmed the ability of garlic to retard lipid peroxidation of cellular
      membranes induced by oxidative stress associated with diabetes. Therefore, garlic
      could normalise oxidative stress in alloxan-induced diabetic rats.

PMID- 23856498
TI  - Growth and inactivation of Salmonella at low refrigerated storage temperatures
      and thermal inactivation on raw chicken meat and laboratory media: mixed effect
      meta-analysis.
AB  - Growth and inactivation regression equations were developed to describe the
      effects of temperature on Salmonella concentration on chicken meat for
      refrigerated temperatures (?10 degrees C) and for thermal treatment temperatures
      (55-70 degrees C). The main objectives were: (i) to compare Salmonella
      growth/inactivation in chicken meat versus laboratory media; (ii) to create
      regression equations to estimate Salmonella growth in chicken meat that can be
      used in quantitative risk assessment (QRA) modeling; and (iii) to create
      regression equations to estimate D-values needed to inactivate Salmonella in
      chicken meat. A systematic approach was used to identify the articles, critically
      appraise them, and pool outcomes across studies. Growth represented in density
      (Log10CFU/g) and D-values (min) as a function of temperature were modeled using
      hierarchical mixed effects regression models. The current meta-analysis analysis
      found a significant difference (P?0.05) between the two matrices - chicken meat
      and laboratory media - for both growth at refrigerated temperatures and
      inactivation by thermal treatment. Growth and inactivation were significantly
      influenced by temperature after controlling for other variables; however, no
      consistent pattern in growth was found. Validation of growth and inactivation
      equations against data not used in their development is needed. 

PMID- 23856499
TI  - Assessing the silent epidemic of malnutrition in Palestinian preschool children.
AB  - BACKGROUND: The nutritional status of children living under conflict is an
      important issue. The aim of the present study is to review all available data on
      malnutrition in preschool Palestinian children and provide objective results
      concerning the epidemic of malnutrition. METHODS: The literature for all research
      on the prevalence of malnutrition on Palestinian children with data collected
      during the period 1998-2007 was reviewed. Der Simonian-Laird Random effects model
      for meta-analysis was applied and cumulative analyses were performed to determine
      time-trends for each outcome measure (iron deficiency anemia [IDA], wasting,
      underweight and stunting). FINDINGS: The results showed that 39.5% of the
      children suffered from IDA, 2.9% from wasting, 4.7% were underweight and 10.9%
      stunted. The cumulative analyses showed a peak in the prevalence of IDA during
      1999, followed by an irregular decrease afterward. The proportion of wasted and
      underweight children peaked during 2002 and 2004, respectively, both showing a
      gradual decline afterward. Chronic malnutrition appears to be almost similar
      during the decade 1998-2007, by demonstrating small, irregular oscillations.
      CONCLUSIONS: Although the prevalence of malnutrition among Palestinian preschool
      children has been improved during the studied period, it still remains high.
      Additionally, the results show that interventions/aid have acute effects on the
      health of children. FUNDING: None.

PMID- 23856500
TI  - Hand rub dose needed for a single disinfection varies according to product: a
      bias in benchmarking using indirect hand hygiene indicator.
AB  - BACKGROUND: The 3ml volume currently used as the hand hygiene (HH) measure has
      been explored as the pertinent dose for an indirect indicator of HH compliance. A
      multicenter study was conducted in order to ascertain the required dose using
      different products. METHOD: The average contact duration before drying was
      measured and compared with references. Effective hand coverage had to include the
      whole hand and the wrist. Two durations were chosen as points of reference: 30s,
      as given by guidelines, and the duration validated by the European standard EN
      1500. Each product was to be tested, using standardized procedures, by three
      nosocomial infection prevention teams, for three different doses (3, 2 and
      1.5ml). RESULTS: Data from 27 products and 1706 tests were analyzed. Depending on
      the product, the dose needed to ensure a 30-s contact duration in 75% of tests
      ranging from 2ml to more than 3ml, and to ensure a contact duration exceeding the
      EN 1500 times in 75% of tests ranging from 1.5ml to more than 3ml. The aftermath
      interpretation is the following: if different products are used, the volume
      utilized does not give an unbiased estimation of the HH compliance. Other
      compliance evaluation methods remain necessary for efficient benchmarking.

PMID- 23856501
TI  - Human papillomavirus (HPV) infection and vaccines: knowledge, attitude and
      perception among female students at the University of Lagos, Lagos, Nigeria.
AB  - AIM: This study sought to determine knowledge of and attitude towards human
      papillomavirus (HPV) infection, HPV-related diseases and HPV vaccines among
      female undergraduate students at the University of Lagos. METHODS: A self
      administered questionnaire was administered between May and July 2010, to 368
      female students aged 16-29years, who were selected from two faculties of the
      University of Lagos using two-stage sampling method. Data collected included:
      socio-demographic characteristics, sexual history, awareness and knowledge of HPV
      infection, cervical cancer and genital warts, and HPV vaccine; the perceived risk
      of acquiring genital HPV infection and developing cervical cancer or genital
      warts, and the willingness to receive an HPV vaccine. RESULTS: Only 64 (17.7%)
      and 52 (14.4%) of the students had ever heard of HPV infection and HPV vaccines
      respectively. The median HPV knowledge on a 15-item score was 2. Overall, only
      11.1% knew that genital HPV infection can cause cervical cancer. Fourteen (6.9%)
      of those who were aware of cervical cancer agreed they were at risk of developing
      the disease. Of the 52 students who had heard of the HPV vaccine, 24 (46.2%) knew
      it was given for cervical cancer prevention and 30 (57.7%) expressed their
      willingness to receive the vaccine. CONCLUSION: The knowledge of and the
      perceived susceptibility to HPV infection and HPV-related diseases among female
      students in the University of Lagos were generally low. The need for a well
      designed HPV-educational program to bridge the knowledge gap cannot be
      overemphasized.

PMID- 23856502
TI  - Rates of diagnosis and treatment of neurological disorders within a prevalent
      population of community-dwelling elderly people in sub-Saharan Africa.
AB  - BACKGROUND: The prevalence of neurological disorders in those aged 70years and
      over in the Hai district of Tanzania has been previously reported. The following
      research reports rates of patient's: treatment seeking, diagnosis and treatment
      within this prevalent population. METHODS: All people identified as having at
      least one neurological disorder in the prevalence study were questioned regarding
      whether they had sought treatment for their disorder, whether they had had a
      previous correct diagnosis and whether they were being currently treated.
      RESULTS: From a background population of 2232 people, 349 people had neurological
      disorders, of whom 225 (64.5%) had sought treatment for their symptoms. Of the
      384 disorders identified in these 349 people, only 14.6% had been diagnosed and
      only 9.9% were receiving appropriate treatment. Males were significantly more
      likely to have been diagnosed and were more likely to have been treated
      appropriately. CONCLUSIONS: Levels of diagnosis and treatment were low, with some
      gender inequality. Reasons for this may include a lack of recognition of the
      condition within the local population and lack of access to appropriate services.
      In the absence of effective primary and secondary preventative measures, and
      effective treatment, the burden of neurological disorders is likely to increase
      with further demographic ageing.

PMID- 23856503
TI  - Occurrence of acute respiratory infection, diarrhea and jaundice among Afghan
      pilgrims, 2010.
AB  - BACKGROUND: Annually 30,000 Afghans attend the Hajj in Saudi Arabia that is one
      of the largest mass gathering events in the world. We aimed to determine the
      prevalence of three syndromes of interest diarrhea, acute respiratory infections
      (ARI) and jaundice-among Hajjis gathering at the four transit sites in
      Afghanistan before, during, and after their voyage. METHODS: A total of 1659
      Hajjis at four transit sites were selected and included a cross-sectional study.
      Information was collected prior Hajjis departure and upon their return from Saudi
      Arabia regarding demographics and experience of diarrhea, ARI and jaundice.
      Standardized case definitions were used for the three health outcomes of
      interest. RESULTS: The occurrence of diarrhea and jaundice remained constant over
      time. However, ARI increased from 1.4% at pre-transit to 4% at transit area and
      37% during the Hajj. ARI rates among residents from the Central and Northern
      regions of Afghanistan were significantly higher at the post-Hajj stage, at 50%
      and 69%, respectively. There was no difference in ARI by sex among Hajjis.
      CONCLUSIONS: There is a need to review the quality and effectiveness of the flu
      vaccine. Authorities should come up with the sound strategies to overcome ARI
      problems during Hajj.

PMID- 23856504
TI  - District level coverage gap in Maternal, Newborn and Child Health care services
      in India.
AB  - India has the highest number of maternal (2010) and child (2009) deaths in the
      world suggesting a poor coverage in Maternal, Newborn and Child Health (MNCH)
      care services. This study assessed the coverage gap in MNCH care across districts
      in India using a robust aggregate Coverage Gap Index (CGI) developed by the
      'Countdown 2008 Equity Analysis Group'. The north-south divide in MNCH care
      coverage gap is apparent. The results derived from this study emphasise the need
      for focused intervention in 210 districts which have a coverage gap of >=50%.

PMID- 23856505
TI  - Further considerations of evaluation competencies in Taiwan.
AB  - A list of evaluator competencies (Stevahn, King, Ghere, & Minnema, 2005) was
      adapted to fit the Taiwanese context by Lee, Altschuld, & Lee (2012). It was
      studied as to how it generalized to a large sample in Taiwan. Likert and Fuzzy
      surveys with needs assessment formats (importance and competence) were mailed via
      random assignment to two groups of participants. The questions for the study
      were: do the modified competencies relate country-wide to Taiwan, did the
      investigation uncover training needs for evaluators, and were there convergent
      rating patterns across the two forms of the instrument? The results supported a
      fit of the modified competencies to the context and convergent validity was
      observed but strong competency needs were not apparent. Reasons for the findings
      and implications for future research are discussed. 

PMID- 23856507
TI  - Mean platelet volume is not associated with bacterial sepsis in newborns.

PMID- 23856508
TI  - Detection of the Wolbachia protein WPIP0282 in mosquito spermathecae:
      implications for cytoplasmic incompatibility.
AB  - Cytoplasmic incompatibility (CI) is a conditional sterility induced by the
      bacterium Wolbachia pipientis that infects reproductive tissues in many
      arthropods. Although CI provides a potential tool to control insect vectors of
      arthropod-borne diseases, the molecular basis for CI induction is unknown. We
      hypothesized that a Wolbachia-encoded, CI-inducing factor would be enriched in
      sperm recovered from spermathecae of female mosquitoes. Using SDS-PAGE and mass
      spectrometry, we detected peptides from the 56 kDa hypothetical protein, encoded
      by wPip_0282, associated with sperm transferred to females by Wolbachia infected
      males. We also detected peptides from the same protein in Wolbachia infected
      ovaries. Homologs of wPip_0282 and the co-transcribed downstream gene, wPip_0283,
      occur as multiple divergent copies in genomes of CI-inducing strains of
      Wolbachia. The operon is located in a genomic context that includes mobile
      genetic elements. The absence of wPip_0282 and wPip_0283 homologs from genomes of
      Wolbachia in filarial nematodes, as well as other members of the Rickettsiales,
      suggests a role as a candidate CI effector. 

PMID- 23856510
TI  - [Does primary prevention contribute to increase social inequalities in health?].
AB  - In France, as in many countries, tackling social inequalities in health is a
      public health priority. However, primary prevention may sometimes contribute to
      increase such inequalities. This article aims to illustrate this point,
      considering the cases of smoking and obesity. The implicit hypotheses of
      prevention regarding its targets are discussed, as well as its stigmatization
      effects. On the one hand, prevention can increase the social differentiation of
      risky behaviors, as it is more effective among wealthier and more educated
      people. On the other hand, prevention policies intending to increase either the
      financial or the symbolic cost of risky behaviors may also increase social
      inequalities. Primary prevention needs more reflexivity regarding its potential
      unintended and deleterious side effects. 

PMID- 23856509
TI  - MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of
      pediatric patients with ulcerative colitis.
AB  - BACKGROUND & AIMS: Altered levels and functions of microRNAs (miRs) have been
      associated with inflammatory bowel diseases (IBDs), although little is known
      about their roles in pediatric IBD. We investigated whether colonic mucosal miRs
      are altered in children with ulcerative colitis (UC). METHODS: We used a library
      of 316 miRs to identify those that regulate phosphorylation of signal transducer
      and activator of transcription 3 (STAT3) in NCM460 human colonocytes incubated
      with interleukin-6. Levels of miR-124 were measured by real-time polymerase chain
      reaction analysis of colon biopsies from pediatric and adult patients with UC and
      patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza
      2'-deoxycytidine (5-AZA). Methylation of the MIR124 promoter was measured by
      quantitative methylation-specific polymerase chain reaction. RESULTS: Levels of
      phosphorylated STAT3 and the genes it regulates (encoding vascular endothelial
      growth factor (VEGF), BCL2, BCLXL, and matrix metallopeptidase 9 [MMP9]) were
      increased in pediatric patients with UC compared with control tissues.
      Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3
      phosphorylation by >= 75% in NCM460 cells; miR-124 had the greatest effect. miR
      124 was down-regulated specifically in colon tissues from pediatric patients with
      UC and directly targeted STAT3 messenger RNA (mRNA). Levels of miR-124 were
      decreased, whereas levels of STAT3 phosphorylation increased in colon tissues
      from pediatric patients with active UC compared with those with inactive disease.
      In addition, levels of miR-124 and STAT3 were inversely correlated in mice with
      experimental colitis. Down-regulation of miR-124 in tissues from children with UC
      was attributed to hypermethylation of its promoter region. Incubation of HCT-116
      colonocytes with 5-AZA up-regulated miR-124 and reduced levels of STAT3 mRNA.
      CONCLUSIONS: miR-124 appears to regulate the expression of STAT3. Reduced levels
      of miR-124 in colon tissues of children with active UC appear to increase
      expression and activity of STAT3, which could promote inflammation and the
      pathogenesis of UC in children.

PMID- 23856511
TI  - Cost effectiveness of adding budesonide/formoterol to tiotropium in COPD in four
      Nordic countries.
AB  - OBJECTIVE: Assess the cost effectiveness of budesonide/formoterol (BUD/FORM)
      Turbuhaler((r))+tiotropium (TIO) HandiHaler((r)) vs. placebo (PBO)+TIO in
      patients with chronic obstructive pulmonary disease (COPD) eligible for inhaled
      corticosteroids/long-acting beta2-agonists (ICS/LABA). METHODS: The cost
      effectiveness analysis was based on the 12-week, randomised, double-blind CLIMB
      trial. The study included 659 patients with pre-bronchodilator forced expiratory
      volume in 1 s <= 50% and >=1 exacerbation requiring systemic glucocorticosteroids
      or antibiotics the preceding year. Patients received BUD/FORM 320/9 MUg bid + TIO
      18 MUg qd or PBO bid + TIO 18 MUg qd. Effectiveness was defined as the number of
      severe exacerbations (hospitalisation/emergency room visit/systemic
      glucocorticosteroids) avoided. A sub-analysis included antibiotics in the
      definition of an exacerbation. Resource use from CLIMB was combined with Danish
      (DKK), Finnish (?), Norwegian (NOK) and Swedish (SEK) unit costs (2010). The
      incremental cost-effectiveness ratios (ICERs) for BUD/FORM + TIO vs. PBO + TIO
      were estimated using descriptive statistics and uncertainty around estimates
      using bootstrapping. Analyses were conducted from the societal and healthcare
      perspectives in Denmark, Finland, Norway and Sweden. RESULTS: From a societal
      perspective, the ICER was estimated at ?174/severe exacerbation avoided in
      Finland while BUD/FORM + TIO was dominant in the other countries. From the
      healthcare perspective, ICERs were DKK 1580 (?212), ?307 and SEK 1573 (?165) per
      severe exacerbation avoided for Denmark, Finland and Sweden, respectively, while
      BUD/FORM + TIO was dominant in Norway. Including antibiotics decreased ICERs by 8
      15%. Sensitivity analyses showed that results were overall robust. CONCLUSION:
      BUD/FORM + TIO represents a clinical and economic benefit to health systems and
      society for the treatment of COPD in the Nordic countries. (ClinicalTrials.gov
      Identifier: NCT00496470).

PMID- 23856512
TI  - Periodontal-prosthodontics in contemporary practice.

PMID- 23856513
TI  - Claudin-7 expression and its association with tumor progression in systemic
      malignancies--reply.

PMID- 23856514
TI  - An etymological "autopsy" of Morgagni's title: De sedibus et causis morborum per
      anatomen indagatis (1761).
AB  - For the Morgagnian anniversaries of 2011 to 2012, the University of Padua
      organized a wide research project, trying to understand Morgagni's contribution
      in his historical context and why he is still considered the father of a new way
      of thinking in medicine, based on anatomoclinical correlations. Calling his
      masterpiece De sedibus et causis morborum per anatomen indagatis, Morgagni placed
      his research in a specific tradition of medical studies: the mechanistic approach
      to medicine, considered new in different European contexts. This approach gave
      Morgagni the theoretical structure to find his anatomopathologic research and the
      revolutionary idea for his time: post mortem dissections could be useful to
      understand pathophysiologic mechanisms and clinical symptoms in the living. 

PMID- 23856515
TI  - V-ets erythroblastosis virus E26 oncogene homolog (avian)/Trefoil factor 3/high
      molecular-weight cytokeratin triple immunostain: a novel tissue-based biomarker
      in prostate cancer with potential clinical application.
AB  - Trefoil factor 3 (TFF3) is associated with various cancers and overexpressed in a
      subset of prostate cancers. Functional studies suggest that v-ets
      erythroblastosis virus E26 oncogene homolog (avian) (ERG) down-regulates TFF3
      expression in hormone-naive prostate cancer. To characterize this inverse
      relationship, we developed a triple immunostain encompassing ERG, TFF3, and high
      molecular-weight cytokeratin. Triple stain was performed on 96 tumors and 52
      benign cases represented in tissue microarrays. Distinct ERG and TFF3 protein was
      expressed in 45% (43/96) and 36% (35/96) of prostate cancers, respectively.
      Coexpression was observed in 5% (5/96) of tumor cases, and 24% (23/96) did not
      express ERG or TFF3. The inverse expression of ERG and TFF3 was significant (P <
      .0001), with 57% (30/53) of ERG-negative tumors demonstrating TFF3 expression.
      Sensitivity and specificity of combined ERG and TFF3 expression in detecting
      prostate cancer were 76% and 96%, respectively. The feasibility of triple
      immunostain protocol was validated in a set of 76 needle biopsies. The
      application of this multiplex in situ biomarker for molecular characterization of
      prostate cancer and as a supplemental diagnostic and prognostic tool in prostate
      needle biopsies should be further explored. 

PMID- 23856516
TI  - Relationship between primary and metastatic testicular germ cell tumors: a
      clinicopathologic analysis of 100 cases.
AB  - Testicular germ cell tumors (GCTs) commonly metastasize to the retroperitoneal
      lymph nodes (RPLNs). We evaluated 100 cases of RPLN dissection specimens with
      viable GCTs after chemotherapy and compared them with their corresponding
      orchiectomy specimens. The mean age of patients was 28 years (range, 15-58
      years). The testicular tumors consisted of mixed GCT (n = 72), teratoma (n = 18),
      seminoma (n = 4), embryonal carcinoma (n = 3), yolk sac tumor (n = 1), and no
      viable tumor (n = 2). Somatic malignant components were found in 5 cases. The
      metastatic tumors in the RPLNs consisted of only teratoma (n = 77) and non
      teratomatous GCT (n = 23). Twenty-one patients had only teratoma in the RPLNs but
      not in the testis, and 10 patients had metastatic non-teratomatous GCT components
      that were not observed in the testis. Six patients had somatic malignant
      components in the RPLNs, but only one of them had such a component in the testis.
      Overall, 13 patients died of disease in a mean of 42 months, and the patients
      with only teratoma in the RPLNs had a lower mortality rate (9%) than those with
      non-teratomatous components (26%) (P = .044). One patient with somatic components
      in the primary GCT and 3 patients with somatic components in the metastases died
      of disease. Our study demonstrates that there is frequent discordance of
      histologic composition between primary and metastatic testicular GCTs. Teratoma
      is the most common component in treated GCTs and is usually associated with a
      more favorable clinical outcome than non-teratomatous GCTs. The presence of
      somatic components in the RPLNs metastasis indicates a poor prognosis. 

PMID- 23856517
TI  - A simple high-throughput method for determination of antiepileptic analogues of
      gamma-aminobutyric acid in pharmaceutical dosage forms using microplate
      fluorescence reader.
AB  - Pregabalin (PGB), gabapentin (GBP), and vigabatrin (VGB) are structural analogues
      of gamma-aminobutyric acid used for the treatment of different forms of epilepsy.
      Their analytical determination is challenging since these molecules have no
      significant UV or visible absorption. Several derivatization methods have been
      developed and used for their determination in bulk or pharmaceutical dosage
      forms. We aimed to develop a high- throughput method using a microplate reader
      with fluorescence detection and simple derivatization with fluorescamine.
      Obtained method involves derivatization step of only 5 min at room temperature
      and simultaneous measurements of 96 samples (lambdaex 395, lambdaem 476 nm) thus
      rendering excellent high-throughput analysis. The method was found to be linear
      with r2>0.998 across investigated analytical ranges of 0.75 to 30.0 ug/mL for
      PGB, 2.00 to 80.0 ug/mL for GBP, and 1.50 to 60.0 ug/mL for VGB. Intraday and
      interday precision values did not exceed 4.93%. The accuracy was ranging between
      96.6 to 103.5%. The method was also found to be specific since used excipients
      did not interfere with the method. The robustness study showed that
      derivatization procedure is more robust than spectrofluorimetric conditions. The
      developed high-throughput method was successfully applied for determination of
      drug content and dissolution profiles in pharmaceutical dosage forms of studied
      antiepileptic drugs.

PMID- 23856518
TI  - Editorial comment.

PMID- 23856519
TI  - Editorial comment.

PMID- 23856521
TI  - Editorial comment.

PMID- 23856522
TI  - Jmjd3 controls mesodermal and cardiovascular differentiation of embryonic stem
      cells.
AB  - RATIONALE: The developmental role of the H3K27 demethylases Jmjd3, especially its
      epigenetic regulation at target genes in response to upstream developmental
      signaling, is unclear. OBJECTIVE: To determine the role of Jmjd3 during mesoderm
      and cardiovascular lineage commitment. METHODS AND RESULTS: Ablation of Jmjd3 in
      mouse embryonic stem cells does not affect the maintenance of pluripotency and
      self-renewal but compromised mesoderm and subsequent endothelial and cardiac
      differentiation. Jmjd3 reduces H3K27me3 marks at the Brachyury promoter and
      facilitates the recruitment of beta-catenin, which is critical for Wnt signal
      induced mesoderm differentiation. CONCLUSIONS: These data demonstrate that Jmjd3
      is required for mesoderm differentiation and cardiovascular lineage commitment.

PMID- 23856524
TI  - Mesoappendix and appendix stump treatment in laparoscopic appendectomy: a
      retrospective study in 1084 patients.
AB  - BACKGROUND: Laparoscopic appendicectomy (LA) rapresents a standard but
      questionable approach in the treatment of acute appendicitis. The scope of this
      study is to show our experience using different methods in the mesoappendix and
      appendix stump treatment. MATERIALS AND METHODS: A retrospective analysis of all
      patient with acute appendicitis that underwent to LA was obtained. The results
      have been analysed compareing the single techniques used in the treatment of
      mesoappendix and appendix stump. RESULTS: The study included 1084 patients
      (M=648; F=436; mean age 28,4 years). During laparoscopic procedure we have
      founded in 296 cases a CAA (27.3%). The rate of conversion to open has resulted
      3,2%; the mean operative time was 57,1'; mean postoperative stay was 2,7 days.
      Eighteen patients have experienced surgical complications. From our data, in the
      treatment of mesoappendix (Clip =863, bipolar coagulation = 165, stapler = 22)
      and the appendix stump (endoloop =784; stapler = 265) we found no statistically
      difference about postoperative stay, and incidence of IAA; the operative time was
      longer (54,2 vs 66' p<0.05) when the surgeon prefered stapling the appendix
      stump; but in this group there was a higher incidence of CAA (35.2 % vs 18.7%).
      CONCLUSIONS: Laparoscopic appendicectomy is safe and effective. We judge that
      there isn't a better technique than others but various options that should be
      evaluated taking care about costs, the experience of the surgeon and the degree
      of inflammation of the appendix.

PMID- 23856523
TI  - Phospholamban knockout breaks arrhythmogenic Ca2+ waves and suppresses
      catecholaminergic polymorphic ventricular tachycardia in mice.
AB  - RATIONALE: Phospholamban (PLN) is an inhibitor of cardiac sarco(endo)plasmic
      reticulum Ca2+ ATPase. PLN knockout (PLN-KO) enhances sarcoplasmic reticulum Ca2+
      load and Ca2+ leak. Conversely, PLN-KO accelerates Ca2+ sequestration and aborts
      arrhythmogenic spontaneous Ca2+ waves (SCWs). An important question is whether
      these seemingly paradoxical effects of PLN-KO exacerbate or protect against Ca2+
      triggered arrhythmias. OBJECTIVE: We investigate the impact of PLN-KO on SCWs,
      triggered activities, and stress-induced ventricular tachyarrhythmias (VTs) in a
      mouse model of cardiac ryanodine-receptor (RyR2)-linked catecholaminergic
      polymorphic VT. METHODS AND RESULTS: We generated a PLN-deficient, RyR2-mutant
      mouse model (PLN-/-/RyR2-R4496C+/-) by crossbreeding PLN-KO mice with
      catecholaminergic polymorphic VT-associated RyR2-R4496C mutant mice. Ca2+ imaging
      and patch-clamp recording revealed cell-wide propagating SCWs and triggered
      activities in RyR2-R4496C+/- ventricular myocytes during sarcoplasmic reticulum
      Ca2+ overload. PLN-KO fragmented these cell-wide SCWs into mini-waves and Ca2+
      sparks and suppressed the triggered activities evoked by sarcoplasmic reticulum
      Ca2+ overload. Importantly, these effects of PLN-KO were reverted by partially
      inhibiting sarco(endo)plasmic reticulum Ca2+ ATPase with 2,5-di-tert
      butylhydroquinone. However, Bay K, caffeine, or Li+ failed to convert mini-waves
      to cell-wide SCWs in PLN-/-/RyR2-R4496C+/- ventricular myocytes. Furthermore, ECG
      analysis showed that PLN-KO mice are not susceptible to stress-induced VTs. On
      the contrary, PLN-KO protected RyR2-R4496C mutant mice from stress-induced VTs.
      CONCLUSIONS: Our results demonstrate that despite severe sarcoplasmic reticulum
      Ca2+ leak, PLN-KO suppresses triggered activities and stress-induced VTs in a
      mouse model of catecholaminergic polymorphic VT. These data suggest that breaking
      up cell-wide propagating SCWs by enhancing Ca2+ sequestration represents an
      effective approach for suppressing Ca2+-triggered arrhythmias.

PMID- 23856525
TI  - Interactions with selected drug renal transporters and transporter-mediated
      cytotoxicity in antiviral agents from the group of acyclic nucleoside
      phosphonates.
AB  - Members of acyclic nucleoside phosphonates (ANPs) possess antiviral and
      antiproliferative activities. However, several clinically important ANPs may
      cause renal injury, most likely due to their active accumulation in the renal
      tubular cells. The goal of this study was to investigate in vitro relationships
      between the affinity of several structurally related potent ANPs to selected
      human transporters and their cytotoxicity. SLC (solute carrier family)
      transporters (hOAT1, hOCT2, hCNT2, hCNT3) and ABC (ATP-binding cassette)
      transporters (MDR1, BCRP), which are typically expressed in the kidney, were
      included in the study. The transport and toxic parameters of the tested compounds
      were compared to those of two clinically approved ANPs, adefovir and tenofovir.
      Transport studies with transiently transfected cells were used as the main method
      in the experiments. Most of the ANPs studied showed the potency to interact with
      hOAT1. GS-9191, a double prodrug of PMEG, displayed an affinity for hOAT1
      comparable with that of adefovir and tenofovir. No significant interaction of the
      tested ANPs with hOCT2, hCNT2 and hCNT3 was observed. Only GS-9191 was found to
      be a strong inhibitor for both MDR1 and BCRP. PMEO-DAPy showed the potency to
      interact with MDR1. Most of the tested substances caused a significant decrease
      in cellular viability in the cells transfected with hOAT1. Only with the
      exclusion of GS-9191, a relatively lipophilic compound, did the in vitro
      cytotoxicity of the ANPs closely correspond to their potential to interact with
      hOAT1. The increased cytotoxicity of the studied ANPs found in OAT1 transfected
      cells was effectively reduced by OAT inhibitors probenecid and quercetin. The
      higher cytotoxicity of the compounds with affinity to hOAT1 proved in the
      inhibitory experiments evidences that ANPs are not only inhibitors but also
      substrates of hOAT1. Any clear relationship between the potency of ANPs to
      inhibit the studied efflux transporters and their cytotoxicity was not
      demonstrated. In conclusion, the study documented that among the studied
      transporters hOAT1 seems to be the decisive determinant for renal handling in
      most of the tested ANPs. This transporter may also play an important role in the
      mechanism of their potential cytotoxic effects. These facts are in good
      accordance with previous findings in the clinically used ANPs. 

PMID- 23856526
TI  - Cell cycle progression, but not genotoxic activity, mainly contributes to
      citrinin-induced renal carcinogenesis.
AB  - Citrinin (CTN) is a food-contaminating mycotoxin that efficiently induces renal
      tumors in rats. However, the modes of carcinogenic action are still unknown,
      preventing assessment of the risks of CTN in humans. In the present study, the
      proliferative effects of CTN and its causal factors were investigated in the
      kidneys of gpt delta rats. In addition, three in vivo genotoxicity assays
      (reporter gene mutation using gpt delta rats and comet and micronucleus assays
      using F344 rats) were performed to clarify whether CTN was genotoxic in vivo. CTN
      was administrated at 20 and 40mg/kg/day, the higher dose being the maximal
      tolerated dose and a nearly carcinogenic dose. In the kidney cortex of gpt delta
      rats, significant increases in the labeling indices of proliferating cell nuclear
      antigen (PCNA)-positive cells were observed at all doses of CTN. Increases in the
      mRNA expression levels of Ccna2, Ccnb1, Ccne1, and its transcription factor E2f1
      were also detected, suggesting induction of cell cycle progression at all tested
      doses of CTN. However, histopathological changes were found only in rats treated
      with the higher dose of CTN, which was consistent with increases in the mRNA
      expression levels of mitogenic factors associated with tissue
      damage/regeneration, such as Hgf and Lcn2, at the same dose. Thus, the
      proliferative effects of CTN may result not only from compensatory reactions, but
      also from direct mitogenic action. Western blot analysis showed that ERK
      phosphorylation was increased at all doses, implying that cell cycle progression
      may be mediated by activation of the ERK pathway. On the other hand, in vivo
      genotoxicity analyses were negative, implying that CTN did not have the potential
      for inducing DNA damage, gene mutations, or chromosomal aberrations. The overall
      data clearly demonstrated the molecular events underlying CTN-induced cell cycle
      progression, which could be helpful to understand CTN-induced renal
      carcinogenesis. 

PMID- 23856527
TI  - Adenosine receptors as potential targets in melanoma.
AB  - Melanoma is one of the most aggressive types of cancer, that is difficult to
      manage clinically. A major feature of melanoma cells is their ability to escape
      immune surveillance. Adenosine receptors play a pivotal role in host immune
      surveillance. A2a (A2aR) and, partially, A2bR receptors mediate the adenosine
      induced immune-suppression, which markedly facilitates tumor
      development/progression. On the contrary, A3R stimulation enhances the anti-tumor
      immune response and thus limits tumor growth. A3R also inhibits the proliferation
      of many cancer cells. Given that A2aR and A3R have profound effects on tumor
      growth and metastasis, they are attractive targets for novel therapeutic anti
      cancer agents. Here, we review the role played by A2aR and A3R in regulating
      cancer pathogenesis, with a focus on melanoma, and the therapeutic potential of
      adenosine receptors pharmacological modulation. 

PMID- 23856528
TI  - Deglycosylation is a key step in biotransformation and lifespan effects of
      quercetin-3-O-glucoside in Caenorhabditis elegans.
AB  - Due to their purported healthful activities, quercetin and other flavonoids are
      being increasingly proposed as nutraceuticals. Quercetin occurs in food as
      glycosides; however, most assays on its activity have been performed with the
      aglycone, despite glycosylation deeply affects compound bioavailability. In this
      work, the uptake and lifespan effects of quercetin-3-O-glucoside (Q3Glc) and
      quercetin have been assessed in Caenorhabditis elegans. Q3Glc was taken up by
      this nematode in a concentration-dependent manner and rapidly deglycosylated to
      quercetin, which was accumulated in the worm and partially biotransformed to
      conjugated metabolites. Significant mean lifespan extension up to 23% compared to
      controls was observed in wild type worms cultivated in the presence of low
      concentrations of Q3Glc (10 MUM and 25 MUM), whereas exposure to greater
      concentrations of Q3Glc (50-200 MUM) caused a reduction in mean and maximum
      lifespan compared with the control. By contrast, treatment of klo-1 and klo-2
      mutant worms lacking beta-glucosidase activity with 200 MUM of Q3Glc led to
      extended mean lifespan (up to 39%), similar to quercetin aglycone at the same
      concentration levels. In those mutants, Q3Glc was accumulated without important
      deglycosylation to quercetin was produced. Taken together, these findings
      indicated that Q3Glc was taken up by the nematode in greater extent than
      quercetin, and that deglycosylation and subsequent aglycone accumulation in the
      worm appeared as key points to explain the observed lifespan effects. The
      obtained results also suggested that facilitated absorption should be more
      important for the uptake of quercetin derivatives than passive diffusion.

PMID- 23856529
TI  - Combined plasma exchange and platelet transfusion in immune-mediated
      thrombocytopenic emergencies.
AB  - Refractory immune-mediated thrombocytopenia (ITP) can be very difficult to
      manage, especially if associated with a hemorrhagic or surgical emergency. We
      report two cases of refractory ITP that were unresponsive to routine therapeutic
      interventions and frequent platelet transfusions. A combination of plasma
      exchange and platelet transfusion successfully raised the platelet count to a
      level that permitted life-saving surgical interventions. Plasma exchange in these
      two cases likely reduced platelet antibodies significantly, decreasing platelet
      destruction. We propose that a trial of combination plasma exchange and platelet
      transfusion can be attempted in emergent thrombocytopenic situations with an
      underlying immune mechanism. 

PMID- 23856530
TI  - Advances in military, field, and austere transfusion medicine in the last decade.
AB  - Two decades of war in south-west Asia has demonstrated the essential role of
      primary resuscitation with blood products in the care of critically injured
      soldiers. This idea has been widely adopted and is being critically tested in
      civilian trauma centers. The need for red cells, plasma and platelets to be
      immediately available in remote locations creates a logistic burden that will
      best be eased by innovative new blood products such as longer-stored liquid RBCs,
      freeze-dried plasma, small-volume frozen platelets, and coagulation factor
      concentrates such as fibrinogen concentrates and prothrombin complex
      concentrates. Such products have long shelf-lives, low logistic burdens of
      weight, fragility, or needs for processing prior to use. Developing and fielding
      a full family of such products will improve field medical care and make products
      available in the evacuation chain. It also will allow treatment in other austere
      environments such as the hundreds of small hospitals in the US which serve as
      Levels 3 and 4 trauma centers but do not currently have thawed plasma or
      platelets available. Such small trauma centers currently care for half of all the
      trauma patients in the country. Proving the new generation of blood products
      work, will help assure their widest availability in emergencies. 

PMID- 23856531
TI  - South African lymphoma study group.

PMID- 23856532
TI  - New tuberculosis tools are here: can we deliver them for maximal impact?

PMID- 23856533
TI  - Assessing the overuse of antibiotics in children with URTIs in Saudi Arabia:
      development of the parental perception on antibiotics scale (PAPA scale).
AB  - BACKGROUND: Antibiotic overuse is influenced by several factors that can only be
      measured using a valid and reliable psychosocial measurement instrument. This
      study aims to establish translation and early stage validation of an instrument
      recently developed by this research team to measure factors influencing the
      overuse of antibiotics in children with upper respiratory tract infections in
      Saudi Arabia. METHOD: The content evaluation panel was composed of area experts
      approached using the Delphi Technique. Experts were provided with the
      questionnaires iteratively, on a three-round basis until consensus on the
      relevance of items was reached independently. Translation was achieved by
      adapting Brislin's model of translation. RESULTS: After going through the
      iterative process with the experts, consensus was reached to 58 items (including
      demographics). Experts also pointed out some issues related to ambiguity and
      redundancy in some items. A final Arabic version was produced from the
      translation process. CONCLUSION: This study produced preliminary validation of
      the developed instrument from the experts' contributions. Then, the instrument
      was translated from English to Arabic. The instrument will undergo further
      validation steps in the future, such as construct validity.

PMID- 23856534
TI  - Gastrointestinal pathogen distribution in symptomatic children in Sydney,
      Australia.
AB  - There is limited information on the causes of paediatric diarrhoea in Sydney.
      This cross-sectional study used clinical and microbiological data to describe the
      clinical features and pathogens associated with gastrointestinal illnesses for
      children presenting to two major public hospitals in Sydney with diarrhoea, for
      the period January 2007-December 2010. Of 825 children who tested positive for an
      enteric pathogen, 430 medical records were reviewed. Adenovirus, norovirus and
      rotavirus were identified in 20.8%, 20.3% and 21.6% of reviewed cases,
      respectively. Younger children were more likely to have adenovirus and norovirus
      compared with rotavirus (P=0.001). More viruses were detected in winter than in
      the other three seasons (P=0.001). Rotavirus presented a distinct seasonal
      pattern with the lowest rates occurring in the warm months and peaking in the
      cooler months. Adenovirus showed a less consistent monthly trend, and norovirus
      detection increased in the cooler months (P=0.008). A decline in the number of
      rotavirus cases was observed after mid-2008. The majority of childhood diarrhoeal
      illnesses leading to hospital presentations in Sydney are caused by enteric
      viruses with most infections following clear seasonal patterns. However, a
      sustained decrease in the incidence of rotavirus infections has been observed
      over the study period. 

PMID- 23856535
TI  - Prevalence of pulmonary tuberculosis among expatriates subjected to medical visa
      screening in Abu Dhabi, United Arab Emirates.
AB  - INTRODUCTION: All applicants for work and/or residence in Abu Dhabi are screened
      for tuberculosis at the time of issuing or renewing their residence visa. The
      purpose of this study is to assess the prevalence of TB among visa applicants and
      the likelihood of testing positive among different subgroups. METHODS: Data from
      the electronic visa screening system was used for a total of 948,504 applicants
      screened for residence in Abu Dhabi from January to December 2010. RESULTS: The
      screening identified 4577 suspected cases of pulmonary tuberculosis (PTB); 1558
      people with chest X-ray findings suggestive of prior PTB; 235 smear-positives;
      and 132 culture-positive cases. The prevalence of active PTB was 39/100,000, with
      new applicants significantly more likely to test positive compared with renewals
      (OR: 2.05, 95% CI: 1.5-2.7, P<.001). People coming from African countries had the
      highest prevalence of TB compared with people from other regions (OR: 21.25, 95%
      CI: 6.72-67.17, P<.001). CONCLUSION: The number of active PTB cases among
      applicants for visa screening is still of a real concern. Without a rigorous
      screening system, the disease can spread to the community and hit other people.
      Certain subgroups were more likely to have the disease; this could provide the
      scientific foundation for future amendments in the screening requirements.

PMID- 23856536
TI  - Correlates of health attitudes among homosexual and bisexual men.
AB  - There is increased emphasis on physician attention to the overall health and
      wellness of homosexual and bisexual men, though little is known about the health
      related attitudes of these groups. This study determined factors associated with
      the health attitudes of homosexual and bisexual men and identified preferred
      sources of health information. For this study, the 2008 ConsumerStyles panel
      survey was used to create three health attitude scales and to determine factors
      associated with each scale. The three scales were labeled: (1) health motivation;
      (2) relationship with health care provider; and (3) self-perception of health
      literacy. In addition to other factors, higher scores for health motivation and
      relationship with health care provider were associated with black compared with
      white men. In contrast, lower scores for self-perception of health literacy were
      associated with black compared with white men. For information on an unfamiliar
      health condition, most homosexual and bisexual men chose the Internet. Black
      homosexual and bisexual men reported being motivated to be healthy and working
      well with their health care provider to manage their health. However, their
      perception of their own health literacy [corrected] was low compared with the
      white men. Attempts to improve health literacy through Internet sites may be
      helpful in improving health attitudes and reducing negative health outcomes.

PMID- 23856537
TI  - The remarkable adaptability of syndromic surveillance to meet public health
      needs.
AB  - The goal of syndromic surveillance is the earlier detection of epidemics,
      allowing a timelier public health response than is possible using traditional
      surveillance methods. Syndromic surveillance application for public health
      purposes has changed over time and reflects a dynamic evolution from the
      collection, interpretation of data with dissemination of data to those who need
      to act, to a more holistic approach that incorporates response as a core
      component of the surveillance system. Recent infectious disease threats, such as
      severe acute respiratory syndrome (SARS), avian influenza (H5N1) and pandemic
      influenza (H1N1), have all highlighted the need for countries to be rapidly aware
      of the spread of infectious diseases within a region and across the globe. The
      International Health Regulations (IHR) obligation to report public health
      emergencies of international concern has raised the importance of early outbreak
      detection and response. The emphasis in syndromic surveillance is changing from
      automated, early alert and detection, to situational awareness and response.
      Published literature on syndromic surveillance reflects the changing nature of
      public health threats and responses. Syndromic surveillance has demonstrated a
      remarkable ability to adapt to rapidly shifting public health needs. This
      adaptability makes it a highly relevant public health tool. 

PMID- 23856538
TI  - Polity and health care expenditures: the association among 159 nations.
AB  - This paper hypothesized that democratic nations, as characterized by Polity IV
      Project regime scores, spend more on health care than autocratic nations and that
      the association reported here is independent of other demographic, health system
      or economic characteristics of nations. WHO Global Observatory data on 159
      nations with roughly 98% of the world's population were examined. Regime scores
      had significant, direct and independent associations with each of four measures
      of health care expenditure. For every unit increment in a nation's regime score
      toward a more democratic authority structure of governance, we estimated
      significant (p<0.05) increments in the percent of GDP expended on health care
      (+0.14%), percent of general government expenditures targeted to health care
      (+0.25%), total per capita expenditures on health (+34.4Int$) and per capita
      general government expenditures (+22.4Int$), while controlling for a population's
      age distribution, life expectancy, health care workforce and system effectiveness
      and gross national income. Moreover, these relationships were found to persist
      across socio-economic development levels. The finding that practices of health
      care expenditure and authority structures of government co-vary is instructive
      about the politics of health and the challenges of advancing global health
      objectives. 

PMID- 23856539
TI  - Pituitary gonadotropin and ovarian gonadotropin receptor transcript levels:
      seasonal and photoperiod-induced changes in the reproductive physiology of female
      Atlantic salmon (Salmo salar).
AB  - In female Atlantic salmon kept at normal light conditions, pituitary follicle
      stimulating hormone beta (fshb) transcript levels were transiently elevated one
      year before spawning, re-increased in February, and remained high during spawning
      in November and in post-ovulatory fish in December. The first increase in plasma
      17b-estradiol (E2), testosterone (T) and gonadosomatic index (GSI) was recorded
      in January; E2 rose up to one month prior to ovulation, while T and GSI kept
      increasing until ovulation. Pituitary luteinizing hormone beta (lhb) transcript
      levels peaked at the time of ovulation. Except for transient changes before and
      after ovulation, ovarian follicle stimulating hormone receptor (fshr) transcript
      amounts were relatively stable at a high level. By contrast, luteinizing hormone
      receptor (lhcgr) transcript levels started out low and increased in parallel to
      GSI and plasma E2 levels. Exposure to continuous light (LL) induced a bimodal
      response where maturation was accelerated or arrested. The LL-arrested females
      showed previtellogenic oil droplet stage follicles or primary yolk follicles
      only, and fshb and E2 plasma levels collapsed while fshr increased. The LL
      accelerated females showed elevated lhb transcript levels and slightly elevated
      E2 levels during early vitellogenesis, and significantly elevated lhcgr E2 and
      GSI levels in late vitellogenesis. We conclude that Fsh-dependent signaling
      stimulates recruitment into and the sustained development through vitellogenesis.
      Up-regulation of lhcgr gene expression during vitellogenesis may reflect an
      estrogenic effect, while elevated fshr gene expression following ovulation or
      during LL-induced arrestment may be associated with ovarian tissue remodeling
      processes. 

PMID- 23856540
TI  - Dexamethasone inhibits corticosterone deposition in feathers of greenfinches.
AB  - Corticosterone (CORT) content of feathers is a potent source of information about
      activation of hypothalamus-pituitary-adrenal (HPA) axis during feather growth,
      which is used for assessment of well-being and stress history of individuals and
      populations in avian studies. However, little is known about factors affecting
      deposition of CORT into feathers and how feather CORT covaries with other markers
      of stress imposed upon individuals during feather growth. We addressed these
      questions by measuring CORT levels in feathers of wild-caught greenfinches
      (Carduelis chloris) brought into captivity. One tail feather was removed from all
      the birds upon arrival to the laboratory and the CORT levels of replacement
      feathers, grown in captivity were recorded. The birds were subjected to
      treatments of immune activation (by injection of phytohaemagglutinin) and
      synthetic glucocorticoid (dexamethasone, DEX) administration. Only DEX injection
      affected feather CORT levels. DEX-injected birds deposited on average 37% less of
      CORT in their feathers than saline-injected birds. Despite significant effects of
      DEX and immune activation treatments on differential leukocyte counts, we did not
      find any correlations between CORT and leukocyte hemoconcentrations or
      heterophil/lymphocyte ratios (a haematological index of stress), measured at
      three stages of feather growth. Our findings provide novel evidence that feather
      CORT levels are sensitive to manipulation of hormonal balance of birds, thereby
      supporting the diagnostic value of feather CORT measurements. However, we did not
      find any evidence about covariation between feather CORT and other markers of
      stress perceived during the period of feather growth. This calls for further
      research on information content of feather CORT, preferably in experiments
      manipulating more diverse array of psychological, immunological and abiotic
      stressors. 

PMID- 23856541
TI  - Real-time study of protein adsorption kinetics in porous silicon.
AB  - This paper presents an optical method for real-time monitoring of protein
      adsorption using porous silicon self-supported microcavities as a label-free
      detection platform. The study combines an experimental approach with a physical
      model for the adsorption process. The proposed model agrees well with
      experimental observations, and provides information about the kinetics of
      diffusion and adsorption of proteins within the pores, which will be useful for
      future experimental designs. 

PMID- 23856542
TI  - Direct grafting of anti-fouling polyglycerol layers to steel and other
      technically relevant materials.
AB  - Direct grafting of hyperbranched polyglycerol (PG) layers onto the oxide surfaces
      of steel, aluminum, and silicon has been achieved through surface-initiated
      polymerization of 2-hydroxymethyloxirane (glycidol). Optimization of the
      deposition conditions led to a protocol that employed N-methyl-2-pyrrolidone
      (NMP) as the solvent and temperatures of 100 and 140  degrees C, depending on the
      substrate material. In all cases, a linear growth of the PG layers could be
      attained, which allows for control of film thickness by altering the reaction
      time. At layer thicknesses >5 nm, the PG layers completely suppressed the
      adhesion of albumin, fibrinogen, and globulin. These layers were also at least
      90% bio-repulsive for two bacteria strains, E. coli and Acinetobacter baylyi,
      with further improvement being observed when the PG film thickness was increased
      to 17 nm (up to 99.9% bio-repulsivity on silicon).

PMID- 23856543
TI  - Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour
      activity, cellular uptake and improved in vivo bioavailability.
AB  - PURPOSE: The aim of the present study was to blend liquid lipids with solid
      lipids to encapsulate curcumin in solid lipid nanoparticles (SLNs), thereby
      improving the dispersibility and chemical stability of curcumin, prolonging its
      antitumour activity and cellular uptake and enhancing its bioavailability.
      METHODS: Curcumin-loaded SLNs (C-SLNs) were prepared by high-pressure
      homogenisation with liquid lipid Sefsol-218((r)). The morphology, stability and
      release of curcumin in the optimised formulation were investigated. The anti
      cancer activity of the formulation was evaluated in MCF-7 cells. Fluorescence
      spectrophotometry was used to quantify cellular uptake of the drug. The
      pharmacokinetic profiles of curcumin in SLNs after intravenous administration
      were studied in rats. RESULTS: Blending Sefsol-218((r)) into a lipid matrix
      reduced the particle size without improving drug loading. An optimised
      formulation consisting of Dynasan 114((r)), Sefsol-218((r)), and Pluronic
      F68((r)) (630:70:300, w/w) loaded with 0.8% drug was prepared. This formulation
      could be dispersed in water with a mean particle size of 152.8 +/- 4.7 nm and a
      90% entrapment efficiency. Curcumin displayed a two-phase sustained release
      profile from C-SLNs with improved chemical stability. Compared to the solubilised
      solution, C-SLNs exhibited prolonged inhibitory activity in cancer cells, as well
      as time-dependent increases in intracellular uptake. After intravenous
      administration to rats, the bioavailability of curcumin was increased by 1.25
      fold. CONCLUSIONS: C-SLNs with improved dispersibility and chemical stability in
      an aqueous system have been successfully developed. C-SLNs may represent a
      potentially useful cancer therapeutic curcumin delivery system.

PMID- 23856544
TI  - Comparison between cucurbiturils and beta-cyclodextrin interactions with
      cholesterol molecules present in Langmuir monolayers used as a biomembrane model.
AB  - Specific surface techniques can probe the interaction of cholesterol (Chol) with
      substances that are able to host and/or sequester this biomolecule, provided that
      the additives are properly assembled at the interface. Reports on inclusion
      complexes of Chol with beta-cyclodextrins exist in the literature. Here we
      compare the interaction of beta-cyclodextrin and cucurbiturils with Chol present
      in Langmuir phospholipid (dipalmitoylphosphatidylcholine, DPPC) monolayers, used
      as a biomembrane model. Cucurbiturils, CB[n], comprise macrocyclic host molecules
      consisting of n glycoluril units. Classic surface pressure curves, dilatational
      surface viscoelasticity measurements, and fluorescence emission spectra and
      images obtained by time-resolved fluorescence of the corresponding Langmuir
      Blodgett films have shown that homologues with 5 and 6 glycoluril units, CB[5]
      and CB[6], do not form inclusion complexes. Higher-order homologues, such as
      CB[7], are likely to complex with Chol with changes in the minimum molecular
      areas recorded for DPPC/Chol monolayers, the fluorescence decay lifetimes, and
      the dilatational surface viscosities of the monolayers generated in the presence
      of these molecules. Moreover, we proof the removal of cholesterol from the
      biomimetic interface in the presence of CB[7] by means of fluorescence spectra
      from the subphase support of monolayers containing fluorescent-labeled Chol. 

PMID- 23856545
TI  - Biocidal and inhibitory activity screening of de novo synthesized surfactants
      against two eukaryotic and two prokaryotic microbial species.
AB  - Thirty-six quaternary ammonium salts, of which 28 structurally different non
      commercially available surfactants, were tested to screen their biocidal and
      inhibitory antimicrobial activity. Their activity was compared to commercially
      available amphiphiles as well as to non-amphiphilic quaternary ammonium salts. As
      target of these compounds four microbial species were employed of which two
      (Saccharomyces cerevisiae and Candida albicans) were important yeast in the food
      and clinical environment and the other two (Escherichia coli and Listeria
      innocua) represented the Gram negative and positive bacteria, respectively. The
      surfactants showed the ability to kill the microbial cells in water solution and
      to variably hamper their growth onto agar medium. The non-amphiphilic compounds
      (which represent analogues of some surfactants used in this study, since they
      have the same head group but no hydrophobic portion) had little effect in
      solution and no effect against the microbial growth on plate. Amphoteric and non
      amphoteric zwitterionic surfactants showed reduced biocidal activity. The most
      active antimicrobial agent was N-tetradecyltropinium bromide (23S) surfactant.
      The presence of cells did not significantly affect the ability to form micelles,
      as demonstrated by comparative conductometric measurements. 

PMID- 23856546
TI  - Site-selective adsorption of protein induced by a metal pattern on a
      poly(ethylene terephthalate) surface.
AB  - A novel technique for inducing site-selective adsorption of protein through
      constructing metal patterns on flexible poly(ethylene terephthalate) surfaces is
      presented. The substrates were first modified by vacuum ultraviolet (VUV)
      irradiation through a photomask to introduce regions with different functional
      groups. Then the designed metal patterns were constructed on the surfaces of VUV
      treated substrates. The surface rearrangement was effectively prevented by
      constructing silver patterns on poly(ethylene terephthalate) surfaces, thus
      significantly improving the stability and selectivity of protein adsorption on
      the surfaces. Moreover, the protein-repulsive layer further reinforced the
      effect. Finally, protein patterns were successfully obtained. As confirmed by
      fluorescence microscope, field emission scanning electron microscopy (FE-SEM), X
      ray photoelectron spectroscopy (XPS), and static water contact angle measurement,
      the protein patterns possess both excellent selectivity and high fidelity.
      Feature size of the protein patterns surrounded by a protein-repulsive layer was
      exactly the same as that of the photomask. And the grain sizes of silver
      particles were approximately 50 nm. This work could potentially be used in
      various fields such as biomedicine, bioelectronic components, and tissue repair
      and replacement, where selective adsorption of protein is desired.

PMID- 23856547
TI  - Molecular mechanism of T-cell protein tyrosine phosphatase (TCPTP) activation by
      mitoxantrone.
AB  - T-cell protein tyrosine phosphatase (TCPTP) is a ubiquitously expressed non
      receptor protein tyrosine phosphatase. It is involved in the negative regulation
      of many cellular signaling pathways. Thus, activation of TCPTP could have
      important therapeutic applications in diseases such as cancer and inflammation.
      We have previously shown that the alpha-cytoplasmic tail of integrin alpha1beta1
      directly binds and activates TCPTP. In addition, we have identified in a large
      scale high-throughput screen six small molecules that activate TCPTP. These small
      molecule activators include mitoxantrone and spermidine. In this study, we have
      investigated the molecular mechanism behind agonist-induced TCPTP activation. By
      combining several molecular modeling and biochemical techniques, we demonstrate
      that alpha1-peptide and mitoxantrone activate TCPTP via direct binding to the
      catalytic domain, whereas spermidine does not interact with the catalytic domain
      of TCPTP in vitro. Furthermore, we have identified a hydrophobic groove
      surrounded by negatively charged residues on the surface of TCPTP as a putative
      binding site for the alpha1-peptide and mitoxantrone. Importantly, these data
      have allowed us to identify a new molecule that binds to TCPTP, but interestingly
      cannot activate its phosphatase activity. Accordingly, we describe here mechanism
      of TCPTP activation by mitoxantrone, the cytoplasmic tail of alpha1-integrin, and
      a mitoxantrone-like molecule at the atomic level. These data provide invaluable
      insight into the development of novel TCPTP activators, and may facilitate the
      rational discovery of small-molecule cancer therapeutics. 

PMID- 23856548
TI  - [Distal reconstruction of the finger with a partial toe transfer in the child].
AB  - Distal reconstruction of the finger or the thumb with a "custom-made"
      arterialized toe transfer in the child is a sophisticated operation. This
      operation can restore an excellent hand function and good cosmetic result with
      reduced morbidity at the donor site. Characteristics of these microsurgical toe
      transfers in the child are the potential of nerve regeneration and the
      conservation of a growth potential of the phalanx. We report 10 cases of
      reconstruction of a part of the distal finger in children (nail, pulp, bone) with
      a high degree of parents' satisfaction. 

PMID- 23856549
TI  - [Comorbid puffy hand syndrome and factitious disorders: an unusual association
      with poor prognosis].
AB  - The authors report an original clinical presentation of factitious disorders of
      the upper extremity in an ex-drug-addict patient with puffy hand syndrome.
      Chronic self-inflicted ulcerations appeared with sequential manner. The patient
      confessed deliberate self-harm and transfer of anxiety on his hands, the aspect
      of which had become intolerable. Association of puffy hand syndrome with comorbid
      psychosis and major depression explained immediate recurrence of ulcerations
      despite fitted medication and long-term psychotherapy. 

PMID- 23856550
TI  - Contribution of arthroscopy in case of septic appearance arthritis of the wrist:
      a nine cases series.
AB  - Septic arthritis of the wrist is a diagnostic and therapeutic emergency.
      Synovectomy and lavage by arthrotomy is often followed by stiffness. The purpose
      of this study was to evaluate the diagnostic and therapeutic contribution of
      emergency arthroscopic synovectomy with intraarticular lavage. Nine patients were
      operated on for wrist pathology with septic appearance. All had signs of local
      inflammation, three showed locoregional inflammation, three were febrile. In one
      patient several joints were involved. Seven patients presented with inflammatory
      or degenerative arthritis. All patients underwent emergency surgery using
      radiocarpal joint puncture, arthroscopic exploration, intraarticular lavage and
      synovectomy at both the radiocarpal and midcarpal joints. The results were
      evaluated by pain, Quick DASH, grip strength, and wrist range of motion. In three
      cases, joint fluid appeared clear, in three it was turbid, and in three purulent.
      Gram stain and culture revealed bacteria in four cases. Synovitis was radiocarpal
      four times, radiocarpal and midcarpal once. In one case, there was radiocarpal
      and midcarpal chondritis. Average pain was 5.3/10 preoperatively and 2/10 at the
      last clinical follow-up visit. Mean grip strength was 23.3 kg on the involved
      side vs. 33.5 kg on the opposite one. Mean flexion was 55 degrees  for the
      involved wrist vs. 68 degrees ; mean extension was 52 degrees  for the affected
      wrist vs. 59 degrees . No patient was reoperated on. In all cases, there was no
      sign of local inflammation, regional lymphadenopathy or systemic infection at the
      last follow-up. One patient died of colon metastatic cancer. Another patient
      developed a severe Complex Regional Pain Syndrome type I (CRPS1). Our results
      suggest three principles of management of wrist arthritis with septic appearance:
      extended surgical indication, emergency operation and arthroscopic procedure.

PMID- 23856551
TI  - [Treatment of Dupuytren's contracture by collagenase injection].
AB  - Dupuytren's disease is a disorder of the palmar aponeurosis responsible for
      apparition of pathological collagen cords that will gradually lead to a digital
      retraction. These cords cause functional disability to the hand with a real
      handicap for the patient. No curative treatment exists currently in this disease.
      Injections of collagenase from Clostridium histolyticum cause lysis of the
      collagen present in the cords and cause an interruption of the palmar cord. It is
      a new treatment in the management of Dupuytren's disease. The use of collagenase
      injection in the treatment of palmar form of Dupuytren's disease gives good
      results in the short and medium terms. It is a simple, minimally invasive
      treatment, several studies have proven its effectiveness and it approximates
      percutaneous needle fasciotomy in its easy use and its indications. Patients
      should be well informed about local reactions and transient pain with the
      injection of C. histolyticum collagenase. Diffusion of this technique is still
      limited by: the assessment of its cost compared to that of other methods of
      treatment and particularly the needle fasciotomy, and the evaluation of results
      over the long-term. 

PMID- 23856552
TI  - Shared understanding in psychiatrist-patient communication: association with
      treatment adherence in schizophrenia.
AB  - OBJECTIVE: Effective doctor-patient communication, including a shared
      understanding, is associated with treatment adherence across medicine. However,
      communication is affected by a diagnosis of schizophrenia and reaching a shared
      understanding can be challenging. During conversation, people detect and deal
      with possible misunderstanding using a conversational process called repair. This
      study tested the hypothesis that more frequent repair in psychiatrist-patient
      communication is associated with better treatment adherence in schizophrenia.
      METHODS: Routine psychiatric consultations involving patients with (DSM-IV)
      schizophrenia or schizoaffective disorder were audio-visually recorded.
      Consultations were coded for repair and patients' symptoms and insight assessed.
      Adherence was assessed six months later. A principal components analysis reduced
      the repair data for further analysis. Random effects models examined the
      association between repair and adherence, adjusting for symptoms, consultation
      length and the amount patients spoke. RESULTS: 138 consultations were recorded,
      118 were followed up. Patients requesting clarification of the psychiatrist's
      talk and the clarification provided by the psychiatrist was associated with
      adherence six months later (OR 5.82, 95% CI 1.31-25.82, p=0.02). CONCLUSION: The
      quality of doctor-patient communication also appears to influence adherence in
      schizophrenia. PRACTICE IMPLICATIONS: Future research should investigate how
      patient clarification can be encouraged among patients and facilitated by
      psychiatrists' communication.

PMID- 23856553
TI  - IWWG news & views.

PMID- 23856554
TI  - Circulating microparticle tissue factor, thromboembolism and survival in
      pancreaticobiliary cancers.
AB  - BACKGROUND: Tissue factor (TF), the physiologic initiator of coagulation, is over
      expressed in pancreatic cancer, and is associated with a pro-coagulant and pro
      angiogenic state. We hypothesized that in patients with pancreaticobiliary
      cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity
      would be associated with thrombosis and worsened survival. PATIENTS AND METHODS:
      Clinical data and plasma were obtained for consecutive patients with PBC seen at
      Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured
      using a TF-dependent FXa generation assay. RESULTS: The study population
      comprised 117 patients, including pancreatic (n=80), biliary (n=34) or unknown
      primary histologically consistent with PBC (n=3). Of these, 52 patients (44.5%)
      experienced thromboembolism, including pulmonary embolism (n=15), deep venous
      thrombosis (n=21) and other arterial or venous events (n=32). Mean TF was 2.15
      (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity >=
      2.5 pg/mL versus 231 days for MP-TF activity<2.5 pg/mL (p<0.0001). In
      multivariate analysis, elevated MP-TF activity was associated with both VTE (OR
      1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5). CONCLUSIONS:
      Elevated circulating MP-TF activity is associated with thrombosis and worsened
      survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants
      further prospective evaluation.

PMID- 23856555
TI  - Association between PAI-1 4G/5G Polymorphisms and osteonecrosis of femoral head:
      a meta-analysis.
AB  - BACKGROUND: The polymorphism of the plasminogen activator inhibitor-1 (PAI-1) 4
      G/5 G gene has been correlated with susceptibility to osteonecrosis of the
      femoral head (ONFH), but study results are controversial. The aim of this study
      was to derive a more precise estimation of the relationship between the PAI-1 4
      G/5 G Gene polymorphism and ONFH by performing a meta-analysis. METHODS: The meta
      analysis was based on five eligible case-control studies involving 419 cases and
      969 controls and summarized data indicating the association between PAI-1
      polymorphism and risk of osteonecrosis of the femoral head. Odds ratios (OR) with
      95% confidence intervals (95% CI) were used to assess the strength of this
      association in the random-effects model or fixed-effects model. RESULTS: A
      significant association between PAI-1 4 G/5 G polymorphism and ONFH
      susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR=1.766, 95% CI 1.279-2.437,
      P=0.001), 4 G/4G vs. 4 G/5 G+5G/5 G (OR=2.050, 95% CI 1.581-2.657, P=0.000), 4
      G/4G vs. 5 G/5G (OR=2.553, 95% CI 1.345-4.846, P=0.004), and 4 G vs. 5 G
      (OR=1.758, 95% CI 1.236-2.500, P=0.002). No significant association between PAI-1
      4 G/5 G polymorphism and ONFH susceptibility was observed for 4 G/5 G vs. 5 G/5G
      (OR=1.327, 95% CI 0.939-1.877, P=0.109). CONCLUSIONS: This meta-analysis
      suggested that 4 G/5 G polymorphism of the PAI-1 gene was a risk factor for ONFH.
      This study also suggests that the PAI-1 4G4G genotype may indicate a risk for
      ONFH.

PMID- 23856556
TI  - Cortico-spinal embodiment of newly acquired, action-related semantic
      associations.
AB  - BACKGROUND: Behavioral and neurophysiological studies indicate that the semantic
      derivation of the motor skills of a given model (e.g., famous tennis or soccer
      athlete) modulates the reactivity of arm and leg cortico-spinal representations
      of an onlooker who performs a categorization task. Information on the possible
      plastic nature of the sensorimotor mapping of action-related knowledge is still
      lacking. OBJECTIVE/HYPOTHESIS: Here we explored the time course of any cortico
      spinal excitability modulation induced by the creation of arbitrary associations
      between a personal name and tennis- or soccer-related motor skills. METHODS: We
      recorded the amplitude of Transcranial Magnetic Stimulation (TMS) Motor Evoked
      Potentials (MEPs) from arm and leg muscles during a categorization task
      concerning names that were learned in association with either soccer players,
      tennis players or control, non-motor, identities (actors). We stimulated the
      cortico-spinal system and recorded the MEPs at three different time points (0-24
      72 h) after the association learning. RESULTS: Coherently with previous
      literature we found a relative dissociation of leg muscles MEPs during reading of
      soccer-associated personal names with respect to tennis ones. Importantly this
      modulation was measured only 72 h after having learned the association. This
      effect was not found in the arm muscle. CONCLUSION: The results suggest that for
      the process of embodying semantic associations in the motor system to take place,
      the strength of the association itself needs to rise above some level of
      consolidation.

PMID- 23856557
TI  - Prdm12 is induced by retinoic acid and exhibits anti-proliferative properties
      through the cell cycle modulation of P19 embryonic carcinoma cells.
AB  - The Prdm (PRDI-BF1-RIZ1 homologous) family is involved in cell differentiation,
      and several Prdms have been reported to methylate histone H3 by intrinsic or
      extrinsic pathways. Here, we report that Prdm12 recruits G9a to methylate histone
      H3 on lysine 9 through its zinc finger domains. Because of the expression of
      Prdm12 in the developmental nervous system, we investigated the role of Prdm12 on
      P19 embryonic carcinoma cells as a model system for neurogenesis. In P19 cells,
      Prdm12 is induced by Retinoic acid (RA). Overproduction of Prdm12 in P19 cells
      impairs cell proliferation and increases the G1 population accompanied by the
      upregulation of p27. In contrast, the knockdown of Prdm12 increases the number of
      cells in a suspension culture of RA-induced neural differentiation. Both the PR
      domain and zinc finger domains are required for the anti-proliferative activity
      of Prdm12. While the data in this study is based on in vitro models, the results
      suggest that Prdm12 is induced by the RA signaling in vivo, and may regulate
      neural differentiation during animal development. 

PMID- 23856558
TI  - Why is autophagy important for melanoma? Molecular mechanisms and therapeutic
      implications.
AB  - As the principle lysosomal mediated mechanism for the degradation of aged or
      damaged organelles and proteins, autophagy (self-eating) is generally considered
      a pro-survival process activated by cells to sustain life in presence of adverse
      environmental conditions such as nutrient shortage and/or in presence of
      cytotoxic compounds. Upon activation, cytoplasmic material is sequestered into
      double-membrane vesicles (autophagosomes) then targeted for degradation by fusion
      with lysosomes (autolysosomes); metabolic activity and cell survival are
      consequently sustained by recycling the degradation products. Basal autophagy
      occurs in almost all cell types, though at different degree, as a finely
      regulated "quality control" process to prevent cell damage, for the demolition of
      cellular structures during cell/tissue remodelling, and to ensure the maintenance
      of cellular homeostasis through recycling cellular components/molecules.
      Autophagy is stimulated in response to both physiological and pathological
      conditions such as starvation, hypoxia and low energy, pathogen infection and
      protein aggregates. Although it's clear that autophagy is also involved in
      cancer, its role, however, is complex since it can both suppress and promote
      tumorigenesis. Consequently, it is generally accepted that while autophagy is
      used by advanced stage cancers to maintain tumour survival, loss of autophagy in
      earlier stages is associated with tumour development. Accordingly, it is now
      apparent that aberrant control of autophagy is among key hallmarks of cancer,
      with several studies now demonstrating this process is deregulated also in
      melanoma.

PMID- 23856559
TI  - Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a
      randomised, placebo-controlled trial.
AB  - BACKGROUND: Laboratory evidence has shown that cannabinoids might have a
      neuroprotective action. We investigated whether oral dronabinol (Delta(9)
      tetrahydrocannabinol) might slow the course of progressive multiple sclerosis.
      METHODS: In this multicentre, parallel, randomised, double-blind, placebo
      controlled study, we recruited patients aged 18-65 years with primary or
      secondary progressive multiple sclerosis from 27 UK neurology or rehabilitation
      departments. Patients were randomly assigned (2:1) to receive dronabinol or
      placebo for 36 months; randomisation was by stochastic minimisation, using a
      computer-generated randomisation sequence, balanced according to expanded
      disability status scale (EDSS) score, centre, and disease type. Maximum dose was
      28 mg per day, titrated against bodyweight and adverse effects. Primary outcomes
      were EDSS score progression (masked assessor, time to progression of >=1 point
      from a baseline score of 4.0-5.0 or >=0.5 points from a baseline score of >=5.5,
      confirmed after 6 months) and change from baseline in the physical impact
      subscale of the 29-item multiple sclerosis impact scale (MSIS-29-PHYS). All
      patients who received at least one dose of study drug were included in the
      intention-to-treat analyses. This trial is registered as an International
      Standard Randomised Controlled Trial (ISRCTN 62942668). FINDINGS: Of the 498
      patients randomly assigned to a treatment group, 329 received at least one dose
      of dronabinol and 164 received at least one dose of placebo (five did not receive
      the allocated intervention). 145 patients in the dronabinol group had EDSS score
      progression (0.24 first progression events per patient-year; crude rate) compared
      with 73 in the placebo group (0.23 first progression events per patient-year;
      crude rate); HR for prespecified primary analysis was 0.92 (95% CI 0.68-1.23;
      p=0.57). Mean yearly change in MSIS-29-PHYS score was 0.62 points (SD 3.29) in
      the dronabinol group versus 1.03 points (3.74) in the placebo group. Primary
      analysis with a multilevel model gave an estimated between-group difference
      (dronabinol-placebo) of -0.9 points (95% CI -2.0 to 0.2). We noted no serious
      safety concerns (114 [35%] patients in the dronabinol group had at least one
      serious adverse event, compared with 46 [28%] in the placebo group).
      INTERPRETATION: Our results show that dronabinol has no overall effect on the
      progression of multiple sclerosis in the progressive phase. The findings have
      implications for the design of future studies of progressive multiple sclerosis,
      because lower than expected progression rates might have affected our ability to
      detect clinical change. FUNDING: UK Medical Research Council, National Institute
      for Health Research Efficacy and Mechanism Evaluation programme, Multiple
      Sclerosis Society, and Multiple Sclerosis Trust.

PMID- 23856560
TI  - Sublingual immunotherapies: the more we know, the more we need to know.

PMID- 23856561
TI  - Chicken liver glutamate dehydrogenase (GDH) demonstrates a histone H3 specific
      protease (H3ase) activity in vitro.
AB  - Site-specific proteolysis of the N or C-terminus of histone tails has emerged as
      a novel form of irreversible post-translational modifications assigned to
      histones. Though there are many reports describing histone specific proteolysis,
      there are very few studies on purification of a histone specific protease. Here,
      we demonstrate a histone H3 specific protease (H3ase) activity in chicken liver
      nuclear extract. H3ase was purified to homogeneity and identified as glutamate
      dehydrogenase (GDH) by sequencing. A series of biochemical experiments further
      confirmed that the H3ase activity was due to GDH. The H3ase clipped histone H3
      products were sequenced by N-terminal sequencing and the precise clipping sites
      of H3ase were mapped. H3ase activity was only specific to chicken liver as it was
      not demonstrated in other tissues like heart, muscle and brain of chicken. We
      assign a novel serine like protease activity to GDH which is specific to histone
      H3.

PMID- 23856562
TI  - Plant phosphoinositide-dependent phospholipases C: variations around a canonical
      theme.
AB  - Phosphoinositide-specific phospholipase C (PI-PLC) cleaves, in a Ca(2+)-dependent
      manner, phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2) into diacylglycerol
      (DAG) and inositol triphosphate (IP3). PI-PLCs are multidomain proteins that are
      structurally related to the PI-PLCzetas, the simplest animal PI-PLCs. Like these
      animal counterparts, they are only composed of EF-hand, X/Y and C2 domains.
      However, plant PI-PLCs do not have a conventional EF-hand domain since they are
      often truncated, while some PI-PLCs have no EF-hand domain at all. Despite this
      simple structure, plant PI-PLCs are involved in many essential plant processes,
      either associated with development or in response to environmental stresses. The
      action of PI-PLCs relies on the mediators they produce. In plants, IP3 does not
      seem to be the sole active soluble molecule. Inositol pentakisphosphate (IP5) and
      inositol hexakisphosphate (IP6) also transmit signals, thus highlighting the
      importance of coupling PI-PLC action with inositol-phosphate kinases and
      phosphatases. PI-PLCs also produce a lipid molecule, but plant PI-PLC pathways
      show a peculiarity in that the active lipid does not appear to be DAG but its
      phosphorylated form, phosphatidic acid (PA). Besides, PI-PLCs can also act by
      altering their substrate levels. Taken together, plant PI-PLCs show functional
      differences when compared to their animal counterparts. However, they act on
      similar general signalling pathways including calcium homeostasis and cell
      phosphoproteome. Several important questions remain unanswered. The cross-talk
      between the soluble and lipid mediators generated by plant PI-PLCs is not
      understood and how the coupling between PI-PLCs and inositol-kinases or DAG
      kinases is carried out remains to be established. 

PMID- 23856563
TI  - Non-invasive measurement of glucose uptake of skeletal muscle tissue models using
      a glucose nanobiosensor.
AB  - Skeletal muscle tissues play a significant role to maintain the glucose level of
      whole body and any dysfunction of this tissue leads to the diabetes disease. A
      culture medium was created in which the muscle cells could survive for a long
      time and meanwhile it did not interfere with the glucose sensing. We fabricated a
      model of skeletal muscle tissues in vitro to monitor its glucose uptake. A
      nanoporous gold as a high sensitive nanobiosensor was then successfully developed
      and employed to detect the glucose uptake of the tissue models in this medium
      upon applying the electrical stimulation in a rapid, and non-invasive approach.
      The response of the glucose sensor was linear in a wide concentration range of 1
      50 mM, with a detection limit of 3 MUM at a signal-to-noise ratio of 3.0. The
      skeletal muscle tissue was electrically stimulated during 24 h and glucose uptake
      was monitored during this period. During the first 3 h of stimulation,
      electrically stimulated muscle tissue consumed almost twice the amount of glucose
      than counterpart non-stimulated sample. In total, the glucose consumption of
      muscle tissues was higher for the electrically stimulated tissues compared to
      those without applying the electrical field.

PMID- 23856564
TI  - A case of an atypically large proximal 15q deletion as cause for Prader-Willi
      syndrome arising from a de novo unbalanced translocation.
AB  - We describe an 11 month old female with Prader-Willi syndrome (PWS) resulting
      from an atypically large deletion of proximal 15q due to a de novo 3;15
      unbalanced translocation. The 10.6 Mb deletion extends from the chromosome 15
      short arm and is not situated in a region previously reported as a common distal
      breakpoint for unbalanced translocations. There was no deletion of the reciprocal
      chromosome 3q subtelomeric region detected by either chromosomal microarray or
      FISH. The patient has hypotonia, failure to thrive, and typical dysmorphic facial
      features for PWS. The patient also has profound global developmental delay
      consistent with an expanded, more severe, phenotype.

PMID- 23856565
TI  - Health conditions of travellers to Saudi Arabia for the pilgrimage to Mecca (Hajj
      and Umra) for 1434 (2013).

PMID- 23856566
TI  - Case reports of hydatid disease.
AB  - Two cases of hydatid cyst were reported in the Microbiology department, Siddartha
      Medical College in 2011. 42 years old female presented with a history of painless
      swelling in the right inguinal region for 5 years which was insidious in onset
      and gradually increasing in size. She developed itching prior to the hospital
      visit. 40 years old male presented with abdominal swelling since 1 year, not
      associated with vomiting or jaundice. Both the patients were from rural
      background. Conclusion. Echinococcus granulosus can cause cystic lesions anywhere
      in the body. High degree of suspicion of hydatid disease is essential in endemic
      areas in cystic lesions.

PMID- 23856567
TI  - HCV infection prevalence in a population recruited at health centers in Jordan.
AB  - BACKGROUND: Jordan lacks statistical data regarding prevalence of HCV. AIM: To
      determine the prevalence of HCV in selected areas of Jordan (north, middle and
      south of Jordan). METHODS: A random sample of 700 patients attending health
      centers was used to determine HCV prevalence. ELISA testing was used to determine
      HCV-Ab positive cases, which were confirmed by PCR testing. RESULTS AND
      CONCLUSION: The study concluded that the prevalence of HCV infection in the
      population recruited from different health centers in Jordan is relatively low
      and estimates a prevalence of 0.42% among all age groups and 0.56% among those
      aged >15 years old.

PMID- 23856568
TI  - A national survey of childhood physical abuse among females in Swaziland.
AB  - OBJECTIVE: This study describes the scope and characteristics of childhood
      physical abuse in a nationally representative sample of 13-24 year-old females in
      Swaziland. The current study also examined health consequences and risk factors
      of childhood physical abuse. METHODS: The study utilized a two-stage cluster
      sampling design in order to conduct the household survey. Retrospective reports
      of childhood physical abuse and relevant risk factors were collected from 1292
      females. Bivariate and multivariate logistic regression models examined
      associations between childhood physical abuse and both health consequences and
      risk factors. RESULTS: Nearly 1 in 5 females in Swaziland has experienced
      childhood physical abuse in their lifetime, with nearly 1 in 20 having
      experienced abuse that was so severe that it required medical attention. A number
      of risk factors for lifetime childhood physical abuse were identified including:
      maternal death prior to age 13; having lived with three or more families during
      their childhood; and having experienced emotional abuse prior to age 13.
      CONCLUSIONS: Preventing childhood physical abuse in Swaziland may be addressed
      through: promoting safe, stable, and nurturing relationships between children and
      their caretakers; addressing social norms that contribute to harsh physical
      punishment; and addressing underlying stressors associated with severe social and
      economic disadvantage.

PMID- 23856569
TI  - Epidemiology of mental health problems in female students: a questionnaire
      survey.
AB  - Mental health as a state of well-being can be affected by gender. The present
      work aims to examine the mental health status in female students and recognize
      its affecting factors. A cross-sectional study on female students of Payame-Noor
      University in West Azerbaijan, Iran, was conducted among 1632 students. Data
      collection tools were the demographic data and the General Health Questionnaires
      (GHQ-28). The results show that 51.5% of the population under study were healthy
      and 48.5% have had mental disorders. Based on the social effects on the mental
      health of students, the correlations between age (p=0.15), location (p=0.29) and
      parental education (p=0.34) with general health status were assessed and there
      were no significant differences between them. However, birth order (p<0.002),
      marital status (p<0.001) and family income (p<0.000) had significant differences
      with regard to mental health status. This study indicates that 43.6% of students
      are suspected to have mental and physical disorders, and the most effective
      factor is the socioeconomic condition. The strong correlation between birth
      order, marital status, and family income and mental health disorders suggests the
      necessity to pay more attention to all these issues in all at-risk students. 

PMID- 23856570
TI  - Perinatal factors and breast cancer risk among Hispanics.
AB  - PURPOSE: This study assessed whether perinatal factors were associated with
      breast cancer among Hispanics, a group with fairly low incidence rates of breast
      cancer. METHODS: Data were used from a case-control study of breast cancer among
      Hispanics aged 30-79 conducted between 2003 and 2008 on the Texas-Mexico border.
      In-person interviews were completed with 188 incident breast cancer cases
      ascertained through surgeons and oncologists, and 974 controls (with respective
      response rates of 97% and 78%). RESULTS: Relative to birth weight 2500-3999g,
      there was no elevation in breast cancer risk for birth weight of >= 4000g (odds
      ratio [OR] 0.76, 95% confidence interval [CI] 0.47-1.21). CONCLUSIONS: The
      results tended to differ slightly from previous studies of this topic perhaps
      owing to the different hormonal milieu among Hispanics relative to Caucasians,
      African Americans and Asians in whom all previous studies of this topic have been
      conducted. Confirmation of these findings in larger studies may assist in
      determining how hormonal mechanisms responsible for breast cancer differ by
      ethnicity.

PMID- 23856571
TI  - Prevalence of self-reported diabetes, hypertension and heart disease in
      individuals seeking State funding in Trinidad and Tobago, West Indies.
AB  - OBJECTIVE: Diabetes, hypertension and heart disease inflict a heavy health burden
      on the Caribbean Republic of Trinidad and Tobago. This study assessed the
      prevalence of self- reported diabetes, hypertension and heart disease in lower
      socioeconomically placed individuals accessing welfare grants. METHOD: Data
      collected between July 2008 and June 2009 were analyzed from 14,793 responses.
      The survey sought information on education, average monthly income, health,
      housing, and household facilities. RESULTS: Self-reported disease prevalence was
      19.5% (95% CI: 18.9-20.2) for diabetes mellitus; 30.2% (95% CI: 29.5-30.9) for
      hypertension; and 8.2% (95% CI: 7.7-8.6) for cardiac disease. Diabetes and
      cardiac disease had equivalent gender frequency; hypertension was more prevalent
      in women (p<.001). Disease prevalence was highest in Indo-Trinidadians, married
      and divorced subjects, non-Christians and increased with age. Those with primary
      education alone were at greatest risk. CONCLUSION: Trinidad and Tobago have a
      high prevalence of hypertension, diabetes and heart disease. Hypertension showed
      gender specificity in women. Prevalence was highest in Indo-Trinidadians,
      increased with age, and primary education alone was a risk factor. Interventions
      to arrest the high prevalence of chronic non-communicable diseases to promote
      wellness are needed in Trinidad and Tobago.

PMID- 23856572
TI  - Trajectories of tuberculosis-specific interferon-gamma release assay responses
      among medical and nursing students in rural India.
AB  - BACKGROUND: Interferon gamma release assays (IGRAs) have been shown to be highly
      dynamic tests when used in serial testing for TB infection. However, there is
      little information demonstrating a clear association between TB exposure and IGRA
      responses over time, particularly in high TB incidence settings. OBJECTIVES: To
      assess whether QuantiFERON-TB Gold In-Tube (QFT) responses are associated with
      occupational TB exposures in a cohort of young health care trainees in India.
      METHODS: All medical and nursing students at Mahatma Gandhi Institute of Medical
      Sciences were approached. Participants were followed up for 18 months; QFT was
      performed 4 times, once every 6 months. Various modeling approaches were used to
      define IFN-gamma trajectories and correlations with TB exposure. RESULTS: Among
      270 medical and nursing trainees, high rates of conversions (6.3-20.9%) and
      reversions (20.0-26.2%) were found depending on the definitions used. Stable
      converters were more likely to have had TB exposure in hospital pre-study. Recent
      occupational exposures were not consistently associated with QFT responses over
      time. CONCLUSION: IFN-gamma responses and rates of change could not be explained
      by occupational exposure investigated. High conversion and subsequent reversion
      rates suggest many health care workers (HCWs) would revert in the absence of
      treatment, either by clearing the infection naturally or due to fluctuations in
      the underlying immunological response and/or poor assay reproducibility. QFT may
      not be an ideal diagnostic test for repeated screening of HCWs in a high TB
      incidence setting.

PMID- 23856573
TI  - Reply of the authors.

PMID- 23856574
TI  - Presence of M540 bodies in human semen: techniques to detect them require
      attention.

PMID- 23856575
TI  - Comparison of gene expression profiles in granulosa and cumulus cells after
      ovulation induction with either human chorionic gonadotropin or a gonadotropin
      releasing hormone agonist trigger.
AB  - OBJECTIVE: To explore differences in follicle transcriptomes in patients having
      oocyte maturation with either a bolus of hCG or GnRHa. DESIGN: Cumulus cells (CC)
      and mural granulosa cells (MGC) were isolated from preovulatory follicles in
      patients undergoing controlled ovarian stimulation, prospectively randomized to
      GnRHa or hCG triggering. SETTING: University-based facilities for clinical
      services and research. PATIENT(S): Twenty women with indication for IVF or
      intracytoplasmic sperm injection treatment were randomly allocated to hCG or GnRH
      agonist (GnRHa) trigger. INTERVENTION(S): MGC and CC were collected from
      individual follicles in connection with oocyte retrieval. MAIN OUTCOME
      MEASURE(S): RNA was extracted, labeled, amplified, and hybridized on
      HumanGene1.0ST GeneChip Affymetrix array. Expression data were robust multichip
      average normalized and compared using Partek and Ingenuity software. Array data
      were confirmed with reverse transcription-polymerase chain reaction analysis.
      RESULT(S): Comparing the transcriptomes between the groups, 391 and 252 genes
      were differentially expressed (fold change >1.5) in CC and MGC, respectively. The
      enriched bionetworks showed that CC genes highly represented "lipid metabolism
      and small molecule biochemistry" (network score, 41), while in MGC, the top
      network was "cardiovascular development and function and cellular movement"
      (network score, 50). For both CC and MGC, the regulator analysis suggested LH as
      the upstream regulator for the difference observed. In CC, the LH receptor was
      more highly expressed after GnRHa trigger, while in MGC, genes involved in
      angiogenesis such as angiopoietin 1 and semaphorin 3A were down- and up
      regulated, respectively, in GnRHa- as compared with hCG-triggered patients.
      CONCLUSION(S): The comparisons between somatic cell transcriptomes from GnRHa-
      and hCG-triggered follicles showed significant functional differences in both CC
      (steroidogenesis) and MGC (angiogenesis) compartments.

PMID- 23856576
TI  - A new way of investigating abnormal semen quality in men with spinal cord injury.

PMID- 23856577
TI  - The adenovirus E4orf4 protein induces a unique mode of cell death while
      inhibiting classical apoptosis.

PMID- 23856578
TI  - Toward the realization of cell therapy: the advent of MAIT cells from iPSCs.

PMID- 23856579
TI  - Unpicking neurodegeneration in a dish with human pluripotent stem cells: one cell
      type at a time.

PMID- 23856580
TI  - Chromatin dynamics: flipping the switch on a chromatin remodeling machine.

PMID- 23856581
TI  - Ribosome-associated chaperones act as proteostasis sentinels.

PMID- 23856582
TI  - Arginine methylation: making its mark on AP-1 gene activation.

PMID- 23856584
TI  - Cancer hallmarks sustained by ectopic activations of placenta/male germline
      genes.

PMID- 23856583
TI  - "Naked" FACT is unstable.

PMID- 23856585
TI  - [Axillary support in breast cancer: survey practice in France].
AB  - OBJECTIVE: To establish an inventory concerning the consistency of current
      medical practices in the management of axillary support for non-metastatic breast
      cancer since the publication of the ACOSOG-Z0011 randomized trial. PATIENTS AND
      METHODS: A descriptive survey practice using a questionnaire sent by email was
      conducted in medical care teams for breast cancer. RESULTS: Forty-eight medical
      teams across the French territory answered to the questionnaire. It has been
      noted that 72.9% of medical teams have said to consistently achieve an additional
      axillary lymph node dissection (ALND) in case of macrometastatic sentinel node
      (SN), 12.5% in case of micrometastatic SN and only 2.1% in isolated tumor cells
      SN. The majority of medical teams (61.9%) claimed they did not perform the
      procedure GS before or after neoadjuvant chemotherapy (NAC). The SN biopsy was
      performed in only 29.1% of teams before and 9% after NAC, outside study. Axillary
      irradiation was performed in case of macrometastatic SN without complementary by
      27.1% of interviewed medical teams and by 4.1% in the case of micrometastic SN.
      DISCUSSION AND CONCLUSION: This survey of practice in patients with breast cancer
      highlights the evolution of medical practice for the axillary management in
      France. It also illustrates the diversity of practices in medical teams and the
      significant compensatory increase in the expansion of radiation fields in
      patients with metastatic SN without additional ALND.

PMID- 23856586
TI  - Hydrolysis for direct esterification of lipids from wet microalgae.
AB  - Hydrolysis of lipids from microalgae under high water content was investigated as
      a pretreatment of direct esterification. Results indicated that the hydrolysis
      process reduced the inhibition by water in FAME production; in addition, FAME
      obtained by esterification of hydrolysates was increased by 181.7% compared to
      FAME obtained by direct transesterification under the same amount of water
      content (80%). This method has great potential in terms of biodiesel production
      from microalgae since it uses no organic solvent, reduces the drying cost and
      lowers the operating cost compared to any other traditional method. 

PMID- 23856587
TI  - Construction and evaluation of an exopolysaccharide-producing engineered
      bacterial strain by protoplast fusion for microbial enhanced oil recovery.
AB  - Enterobacter cloacae strain JD, which produces water-insoluble biopolymers at
      optimal temperature of 30 degrees C, and a thermophilic Geobacillus strain were
      used to construct an engineered strain for exopolysaccharide production at high
      temperatures by protoplast fusion. The obtained fusant strain ZR3 produced
      exopolysaccharides at up to 45 degrees C with optimal growth temperature at 35
      degrees C. The fusant produced exopolysaccharides of approximately 7.5 g/L or
      more at pH between 7.0 and 9.0. The feasibility of the enhancement of crude oil
      recovery with the fusant was tested in a sand-packed column at 40 degrees C. The
      results demonstrated that bioaugmentation of the fusant was promising approach
      for MEOR. Mass growth of the fusant was confirmed in fermentor tests.

PMID- 23856588
TI  - Optimization of the ultrasonic assisted removal of methylene blue by gold
      nanoparticles loaded on activated carbon using experimental design methodology.
AB  - The present study was focused on the removal of methylene blue (MB) from aqueous
      solution by ultrasound-assisted adsorption onto the gold nanoparticles loaded on
      activated carbon (Au-NP-AC). This nanomaterial was characterized using different
      techniques such as SEM, XRD, and BET. The effects of variables such as pH,
      initial dye concentration, adsorbent dosage (g), temperature and sonication time
      (min) on MB removal were studied and using central composite design (CCD) and the
      optimum experimental conditions were found with desirability function (DF)
      combined response surface methodology (RSM). Fitting the experimental equilibrium
      data to various isotherm models such as Langmuir, Freundlich, Tempkin and Dubinin
      Radushkevich models show the suitability and applicability of the Langmuir model.
      Analysis of experimental adsorption data to various kinetic models such as pseudo
      first and second order, Elovich and intraparticle diffusion models show the
      applicability of the second-order equation model. The small amount of proposed
      adsorbent (0.01 g) is applicable for successful removal of MB (RE>95%) in short
      time (1.6 min) with high adsorption capacity (104-185 mg g(-1)).

PMID- 23856590
TI  - Vehicle-based studies of driving in the real world: the hard truth?
AB  - Real-world studies of driving behaviour and safety have face validity and have
      the distinct advantage of focussing on driving in its natural habitat. But their
      very naturalism can lead to problems with confounds and with noise in the data.
      This paper reviews the three major categories of on-road studies - controlled
      observation, field operational tests and naturalistic driving studies - and
      discusses the major applications of each study type. It also assesses some of the
      methodological issues that arise in one or more category of study. 

PMID- 23856589
TI  - Imatinib mesylate (Gleevec) induces human corpus cavernosum relaxation by
      inhibiting receptor tyrosine kinases (RTKs): identification of new RTK targets.
AB  - OBJECTIVE: To evaluate the effect of the tyrosine kinase inhibitor imatinib
      mesylate (Gleevec) on human corpus cavernosum (HCC) smooth muscle tone. METHODS:
      HCC were obtained from 18 erectile dysfunction (ED) patients undergoing penile
      prosthesis surgery. The effects of imatinib in HCC strips were investigated in
      the presence of various inhibitors. The human phosphoreceptor protein tyrosine
      kinase (PTK) array (Proteome Profiler Array) detected changes in receptor
      phosphorylation before and after imatinib. Immunohistochemistry was used to
      localize phosphorylated c-kit (CD117/stem cell factor) in HCC smooth muscle
      cells. RESULTS: Phenylephrine-induced contraction in HCC was significantly
      inhibited by imatinib (97.7% +/- 2.3%). l-nitro-arginine methyl ester (l-NAME) or
      guanylyl cyclase inhibitor [1H-1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ)
      alone did not reverse the effect of imatinib, but suppressed this response in
      combination (18.0% +/- 0.6%). The K(+) channel blockers (apamin and tetraethyl
      ammonium) decreased the imatinib-induced relaxation by 64% and 51%, respectively.
      PTK microarray analysis of 42 different phospho-receptor tyrosine kinases showed
      14 were clearly activated in HCC. Imatinib treatment significantly inhibited
      phosphorylation of PTKs. A high level of CD117/c-kit-positive immunostaining was
      detected in untreated HCC smooth muscle, but not in treated HCC. CONCLUSION:
      Imatinib caused HCC smooth muscle relaxation in vitro mediated by nitric
      oxide/guanosine monophosphate signaling, involving the large-conductance Ca(2+)
      activated K(+)-channels (BK(Ca)) or by inhibiting the upregulated PTK pathway.
      These results suggest that imatinib may also benefit erectile dysfunction
      patients who are not responsive to phosphodiesterase-5 inhibitors.

PMID- 23856591
TI  - Dissecting karyotypic patterns in non-hyperdiploid multiple myeloma: an overview
      on the karyotypic evolution.
AB  - BACKGROUND: Multiple myeloma (MM) is a plasma cell disorder characterized by the
      presence of specific genetic and cytogenetic aberrations that define unique
      subgroups with different outcomes. On the basis of the ploidy status, MM can be
      subdivided into hyperdiploid MM (H-MM) and non-hyperdiploid MM (NH-MM). NH-MM is
      an entity that encompasses hypodiploid, pseudodiploid, and near tetraploid MM and
      is associated with a higher number of immunoglobulin heavy-chain (IgH)
      translocations. MATERIALS AND METHODS: We have systematically analyzed the
      structure of the karyotypic evolution in NH-MM and identified several genetic
      features of their complex karyotypic patterns. RESULTS: On the basis of
      statistical models used in complex karyotypes, we were able to identify the
      temporal order in which the genetic aberrations occur in NH-MM. In this analysis,
      whole chromosome losses and IgH translocations were commonly seen, and -13/13q-
      and t14q32 were defined as early genetic events in the karyotypic evolution of NH
      MM. Furthermore, chromosome 1 and 17 abnormalities were associated with a late
      karyotypic phase of evolution consistent with the recognized pattern of acquired
      events deemed to be associated with these type of genetic aberrations.
      CONCLUSION: Accumulation of genetic aberrations in NH-MM above a threshold
      results in malignant transformation.

PMID- 23856593
TI  - Nanobiotechnology: synthetic biology meets materials science.
AB  - Nanotechnology, the area of science focused on the control of matter in the
      nanometer scale, allows ground-breaking changes of the fundamental properties of
      matter that are often radically different compared to those exhibited by the bulk
      counterparts. In view of the fact that dimensionality plays a key role in
      determining the qualities of matter, the realization of the great potential of
      nanotechnology has opened the door to other disciplines such as life sciences and
      medicine, where the merging between them offers exciting new applications, along
      with basic science research. The application of nanotechnology in life sciences,
      nanobiotechnology, is now having a profound impact on biological circuit design,
      bioproduction systems, synthetic biology, medical diagnostics, disease therapy
      and drug delivery. This special issue is dedicated to the overview of how we are
      learning to control biopolymers and biological machines at the molecular- and
      nanoscale. In addition, it covers far-reaching progress in the design and
      synthesis of nanoscale materials, thus enabling the construction of integrated
      systems in which the component blocks are comparable in size to the chemical and
      biological entities under investigation. 

PMID- 23856592
TI  - Engineering cell-cell signaling.
AB  - Juxtacrine cell-cell signaling mediated by the direct interaction of adjoining
      mammalian cells is arguably the mode of cell communication that is most
      recalcitrant to engineering. Overcoming this challenge is crucial for progress in
      biomedical applications, such as tissue engineering, regenerative medicine,
      immune system engineering and therapeutic design. Here, we describe the
      significant advances that have been made in developing synthetic platforms
      (materials and devices) and synthetic cells (cell surface engineering and
      synthetic gene circuits) to modulate juxtacrine cell-cell signaling. In addition,
      significant progress has been made in elucidating design rules and strategies to
      modulate juxtacrine signaling on the basis of quantitative, engineering analysis
      of the mechanical and regulatory role of juxtacrine signals in the context of
      other cues and physical constraints in the microenvironment. These advances in
      engineering juxtacrine signaling lay a strong foundation for an integrative
      approach to utilize synthetic cells, advanced 'chassis' and predictive modeling
      to engineer the form and function of living tissues.

PMID- 23856594
TI  - The effect of recovery coaches for substance-involved mothers in child welfare:
      impact on juvenile delinquency.
AB  - Despite the documented relationship between parental substance abuse and youth
      delinquency, the effects of parental interventions on delinquency outcomes are
      unknown. Such interventions are particularly vital for families in the child
      welfare system who are at heightened risk for both parental substance involvement
      and youth delinquency. The current study tested the impact of intensive case
      management in the form of a recovery coach for substance-involved mothers on
      youth delinquency outcomes among a randomized sample of 453 families involved in
      a Title IV-E experimental waiver demonstration in Cook County, Illinois. In
      comparison to control group participants, families enrolled in the Alcohol and
      Other Drug Abuse (AODA) waiver demonstration experienced a lower rate of juvenile
      arrest, net of factors such as demographic characteristics, primary drug of
      choice, and time spent in substitute care. Findings support efforts to curb
      delinquency among child-welfare involved youth by providing recovery coaches to
      their substance abusing or dependent parents. 

PMID- 23856595
TI  - Zoonotic potential of Giardia.
AB  - Giardia duodenalis (syn. Giardia lamblia and Giardia intestinalis) is a common
      intestinal parasite of humans and mammals worldwide. Assessing the zoonotic
      transmission of the infection requires molecular characterization as there is
      considerable genetic variation within G. duodenalis. To date eight major genetic
      groups (assemblages) have been identified, two of which (A and B) are found in
      both humans and animals, whereas the remaining six (C to H) are host-specific and
      do not infect humans. Sequence-based surveys of single loci have identified a
      number of genetic variants (genotypes) within assemblages A and B in animal
      species, some of which may have zoonotic potential. Multi-locus typing data,
      however, has shown that in most cases, animals do not share identical multi-locus
      types with humans. Furthermore, interpretation of genotyping data is complicated
      by the presence of multiple alleles that generate "double peaks" in sequencing
      files from PCR products, and by the potential exchange of genetic material among
      isolates, which may account for the non-concordance in the assignment of isolates
      to specific assemblages. Therefore, a better understanding of the genetics of
      this parasite is required to allow the design of more sensitive and variable
      subtyping tools, that in turn may help unravel the complex epidemiology of this
      infection. 

PMID- 23856596
TI  - Microarray analysis of the human antibody response to synthetic Cryptosporidium
      glycopeptides.
AB  - Glycoproteins expressed by Cryptosporidium parvum are immunogenic in infected
      individuals but the nature of the epitopes recognised in C. parvum glycoproteins
      is poorly understood. Since a known immunodominant antigen of Cryptosporidium,
      the 17kDa glycoprotein, has previously been shown to bind to lectins that
      recognise the Tn antigen (GalNAcalpha1-Ser/Thr-R), a large number of
      glycopeptides with different Tn valency and presentation were prepared. In
      addition, glycopeptides were synthesised based on a 40kDa cryptosporidial
      antigen, a polymorphic surface glycoprotein with varying numbers of serine
      residues, to determine the reactivity with sera from C. parvum-infected humans.
      These glycopeptides and non-glycosylated peptides were used to generate a
      glycopeptide microarray to allow screening of sera from C. parvum-infected
      individuals for the presence of IgM and IgG antibodies. IgG but not IgM in sera
      from C. parvum-infected individuals bound to multivalent Tn antigen epitopes
      presented on glycopeptides, suggesting that glycoproteins from C. parvum that
      contain the Tn antigen induce immune responses upon infection. In addition,
      molecular differences in glycosylated peptides (e.g. substituting Ser for Thr) as
      well as the site of glycosylation had a pronounced effect on reactivity. Lastly,
      pooled sera from individuals infected with either Toxoplasma or Plasmodium were
      also tested against the modified Cryptosporidium peptides and some sera showed
      specific binding to glycopeptide epitopes. These studies reveal that specific
      anti-glycopeptide antibodies that recognise the Tn antigen may be useful
      diagnostically and in defining the roles of parasite glycoconjugates in
      infections. 

PMID- 23856597
TI  - Hematoxylin staining reveals a decrease in nucleolar diameter of pig oocytes
      before germinal vesicle breakdown.
AB  - During oocyte growth, the morphology of the nucleolus changes into a compact and
      homogenous structure. The compact nucleoli in full-grown oocytes are not stained
      by aceto-orcein staining or immunofluorescence staining. In this study, we
      developed a hematoxylin staining method for pig oocytes in whole-mount
      preparations to visualize the nucleoli. Nucleoli of growing and full-grown
      oocytes were stained blue with hematoxylin. Using this staining method, the
      changes in the oocyte nucleolus during maturation were examined. The nucleolar
      diameter gradually decreased in maturing oocytes (10.7 +/- 0.1 MUm to 9.0 +/- 0.7
      MUm, P<0.05) before germinal vesicle breakdown (GVBD). The results suggest that
      the nucleolar volume of oocytes decreases before GVBD. 

PMID- 23856598
TI  - Analytical design of fractional-order proportional-integral controllers for time
      delay processes.
AB  - A new design method of fractional-order proportional-integral controllers is
      proposed based on fractional calculus and Bode's ideal transfer function for a
      first-order-plus-dead-time process model. It can be extended to be applied to
      various dynamic models. Tuning rules were analytically derived to cope with both
      set-point tracking and disturbance rejection problems. Simulations of a broad
      range of processes are reported, with each simulated controller being tuned to
      have a similar degree of robustness in terms of resonant peak to other reported
      controllers. The proposed controller consistently showed improved performance
      over other similar controllers and established integer PI controllers. 

PMID- 23856599
TI  - H2 control of linear uncertain systems considering input quantization with
      encoder/decoder mismatch.
AB  - In this paper, an H2 control design for linear uncertain systems with input
      quantization in the presence of more general encoder/decoder mismatch is
      investigated. The construction of the control law includes two parts: linear part
      and nonlinear part. The gain of the linear part is derived from linear matrix
      inequalities (LMIs), and the linear part of the control law is designed for
      achieving the H2 performance against system characteristic matrix uncertainty and
      encoder/decoder mismatch. The nonlinear part is designed to eliminate the
      influence of external disturbance and quantization error. Finally, examples are
      provided to illustrate the effectiveness of the proposed method. 

PMID- 23856600
TI  - Commentary: on better research and writing in clinical epilepsy.

PMID- 23856602
TI  - Treatment of co-occurring alcohol dependence and perpetration of intimate partner
      violence: the role of anger expression.
AB  - The purpose of the current study was to examine the role of high self-reported
      anger on violence and substance use across treatment. Seventy-three, alcohol
      dependent males, with a domestic violence arrest within the past year, completed
      baseline anger measures and engaged in a 12 week cognitive behavioral therapy or
      12 step facilitation group. Monthly assessments of substance use and violence
      were completed. At baseline, participants high on anger expression reported more
      physical violence in the prior month and more violent arrests. Participants high
      on anger expression had a greater proportion of positive breathalyzers across
      treatment, higher frequency of reported drug use across treatment, and higher
      reported frequency of verbal violence at discharge. These findings suggests that
      participants who are high on anger expression may need longer-term or more
      intensive treatments to maintain gains made during treatment because of the
      increased risk of relapse to both substance use and violence.

PMID- 23856601
TI  - Training workshops positively impact beliefs about contingency management in a
      nationwide dissemination effort.
AB  - In 2011, the Veterans Administration called for nationwide implementation of
      contingency management (CM) in its intensive outpatient substance use disorders
      treatment programs, and this study evaluated the impact of the initial 1 and 1/2
      day training workshops on knowledge and perceptions about CM among 159 clinical
      leaders from 113 clinics. Workshop attendance significantly increased CM-related
      knowledge (d=1.88) and changed attendees' perceptions of CM (ds=0.26-0.74).
      Endorsement of barriers to CM adoption decreased and positive impressions of CM
      increased. These perceptions about CM emerged as key correlates of post-training
      preparedness to implement CM. Results suggest that training workshops can be an
      effective avenue for increasing CM-related knowledge, as well as addressing
      persistent misperceptions about CM that may impede adoption efforts. Continued
      efforts to introduce educational materials and offer training and consultation
      opportunities may increase understanding about this evidence-based intervention
      among clinicians, thereby leading to improved patient outcomes. 

PMID- 23856603
TI  - Effect of cardiac compressions and hypothermia treatment on cardiac troponin I in
      newborns with perinatal asphyxia.
AB  - BACKGROUND: The American Heart Association, the European Resuscitation and the
      International Liaison Committee issued new neonatal resuscitation guidelines
      (2010) where therapeutic hypothermia is introduced after hypoxic-ischaemic
      encephalopathy (HIE) in term infants to prevent brain injury. Our study aimed to
      investigate whether hypothermia can reduce the release of a cardiac cellular
      marker, cardiac troponin I (cTnI), in HIE infants compared to normothermia care,
      if cTnI can be used as a prognostic marker for long term neuro-developmental
      outcome and if cardiac compression at birth affects the level of cTnI. METHODS:
      We retrospectively collected resuscitation data at birth and cTnI levels for the
      first 3 days in HIE infants who fulfilled cooling entry criteria. These infants
      received either normothermia care or induced hypothermia treatment in the
      neonatal period and were then followed up and tested by standard cognitive and
      motor assessments. The outcome is defined as death, disability or good. RESULTS:
      We confirmed an increase in cTnI after cardiac compressions (p=0.003, Mann
      Whitney test). We found that hypothermia significantly reduced the release of
      cTnI (peak level and area under the curve within 24h of age), p=0.002, linear
      regression. Receiver operating characteristic curves showed a level of cTnI at 24
      h of age <0.22 ng/ml for normothermic and <0.15 ng/ml for hypothermic infants
      predicts a good outcome. CONCLUSIONS: Our results suggest that hypothermia is
      cardio protective after HIE. The level of cTnI at 24h of age is a good prognostic
      marker for neuro-developmental outcome at 18-22 months in both normothermia and
      hypothermia infants.

PMID- 23856604
TI  - Medical students teach Basic Life Support to non-medical students: a pilot study.

PMID- 23856605
TI  - High yield purification of nanobodies from the periplasm of E. coli as fusions
      with the maltose binding protein.
AB  - Nanobodies (Nbs) are single domain antibodies based on the variable domains of
      heavy chain only antibodies (HCAbs) found in camelids, also referred to as VHHs.
      Their small size (ca. 12-15kDa), superior biophysical and antigen binding
      properties have made Nbs very attractive molecules for multiple biotechnological
      applications, including human therapy. The most widely used system for the
      purification of Nbs is their expression in the periplasm of Escherichia coli with
      a C-terminal hexa-histidine (His6) tag followed by immobilized metal affinity
      chromatography (IMAC). However, significant variability in the expression levels
      of different Nbs are routinely observed and a single affinity chromatography step
      is often not sufficient to obtain Nbs of high purity. Here, we report an
      alternative method for expression and purification of Nbs from the periplasm of
      E. coli based on their fusion to maltose binding protein (MBP) in the N-terminus
      and His6 tag in the C-terminus (MBP-NbHis6). Soluble MBP-NbHis6 fusions were
      consistently expressed at high levels (?12mg/L of induced culture in shake
      flasks) in the periplasm of E. coli HM140, a strain deficient in several
      periplasmic proteases. Highly pure MBP-NbHis6 fusions and free NbHis6 (after site
      specific proteolysis of the fusions), were recovered by amylose and metal
      affinity chromatography steps. The monomeric nature of the purified NbHis6 was
      determined by gel filtration chromatography. Lastly, we demonstrated by ELISA
      that both monomeric NbHis6 and MBP-NbHis6 fusions retained antigen binding
      activity and specificity, thus facilitating their direct use in antigen
      recognition assays.

PMID- 23856606
TI  - Mitochondrial proteomic analysis of human host cells infected with H3N2 swine
      influenza virus.
AB  - Swine influenza viruses (SIV) are zoonotic pathogens that pose a potential threat
      to human health. In this study, we analyzed the differential mitochondrial
      proteomes of H3N2 SIV-infected human lung A549 cells using two-dimensional gel
      electrophoresis (2-DE) followed by matrix-assisted laser desorption ionization
      time-of-flight/time-of-flight (MALDI-TOF/TOF) analysis. In the comparative
      analysis, 24 altered proteins (13 upregulated and 11 downregulated) were
      identified in the mitochondria of H3N2 SIV-infected cells; these proteins were
      involved in cell-to-cell signaling and interaction, cellular movement, and post
      translational modification. Moreover, the transcriptional profiles of 16 genes
      corresponding to the identified proteins were estimated by real time RT-PCR. IPA
      analysis suggested that the differentially expressed proteins were clustered
      primarily into the mammalian target of rapamycin (mTOR) and d-glucose signaling
      pathways. In addition, oxidative phosphorylation and integrin signaling appeared
      to be major pathways modulated in the mitochondria of infected cells. We further
      demonstrated that apolipoprotein L2 was upregulated in the cytoplasm and
      translocated to mitochondria during virus infection. These results were verified
      by Western blot analysis coupled with confocal microscopy. Collectively, the
      mitochondrial proteome data provide insights to further understand the underlying
      mechanisms of H3N2 SIV cross-species infection. BIOLOGICAL SIGNIFICANCE: In
      recent years, proteomics has emerged as an indispensable tool to unveil the
      complex molecular events in virology. we firstly perform mitochondrial proteomic
      profiles of human cells infected with H3N2 subtype SIV to understand virus-host
      interactions, and 24 differentially expressed proteins in mitochondrial proteomes
      were identified in SIV-infected cells. The proteins that were identified to have
      differential expression were involved in cell-to-cell signaling and interaction,
      post-translational modification, cell morphology, cellular assembly, cell death,
      and energy production. Furthermore, Western blot analysis and a confocal assay
      further demonstrated that the cellular protein APOL2 partially co-localized with
      mitochondria after virus infection. This is a very important discovery in the
      underlying replication and pathogenesis of SIV which provides a potential target
      clue for the design of anti-SIV drugs. Our results will inspire basic study on
      SIV infection and drive the understanding for replication and pathogenesis of SIV
      to control this disease.

PMID- 23856607
TI  - Developments in biobanking workflow standardization providing sample integrity
      and stability.
AB  - Recommendations and outlines for standardization in biobanking processes are
      presented by a research team with long-term experience in clinical studies. These
      processes have important bearing on the use of samples in developing assays.
      These measurements are useful to document states of health and disease that are
      beneficial for academic research, commercial healthcare, drug development
      industry and government regulating agencies. There is a need for increasing
      awareness within proteomic and genomic communities regarding the basic concepts
      of collecting, storing and utilizing clinical samples. Quality control and sample
      suitability for analysis need to be documented and validated to ensure data
      integrity and establish contexts for interpretation of results. Standardized
      methods in proteomics and genomics are required to be practiced throughout the
      community allowing datasets to be comparable and shared for analysis. For
      example, sample processing of thousands of clinical samples, performed in 384
      high-density sample tube systems in a fully automated workflow, preserves sample
      content and is presented showing validation criteria. Large studies will be
      accompanied by biological and molecular information with corresponding clinical
      records from patients and healthy donors. These developments position biobanks of
      human patient samples as an increasingly recognized major asset in disease
      research, future drug development and within patient care. BIOLOGICAL
      SIGNIFICANCE: The current manuscript is of major relevance to the proteomic and
      genomic fields, as it outlines the standardization aspects of biobanking and the
      requirements that are needed to run future clinical studies that will benefit the
      patients where OMICS science will play a major role. A global view of the field
      is given where best practice and conventional acceptances are presented along
      with ongoing large-scale biobanking projects. The authors represent broadly
      stakeholders that cover the academic, pharma, biotech and healthcare fields with
      extensive experience and deliveries. This contribution will be a milestone paper
      to the proteomic and genomic scientists to present data in the future that will
      have impact to the life science area. This article is part of a Special Issue
      entitled: Standardization and Quality Control in Proteomics.

PMID- 23856608
TI  - Analysis of protein species differentiation among mycobacterial low-Mr-secreted
      proteins by narrow pH range Immobiline gel 2-DE-MALDI-MS.
AB  - Secreted proteins of bacteria are preferentially capable of interacting with host
      cells and are therefore of special biological and medical interest. Narrow pH
      range 2-DE and MALDI-TOFTOF-MS combine high-resolution protein separation with
      highly sensitive identification of proteins. Secreted proteins of Mycobacterium
      tuberculosis were separated at the protein species level, distinguishing
      different protein species of one protein. We focused on the pI range 4.0-4.7 and
      the Mr range 6-20kDa of the 2-DE pattern. Out of 128 analyzed spots, 121 were
      identified resulting in 33 different proteins with 277 different protein species,
      accumulating in a mean of 8.4 protein species per protein. Overrepresentation was
      found for the protein classes "virulence, detoxification, adaption", "information
      pathways", "cell wall and cell processes" and "intermediary metabolism and
      respiration". Thus far, 15 protein species of the ESX-1 family are characterized
      with 100% sequence coverage. More automated 2-DE procedures and more sensitive
      identification techniques are required for complete characterization of all of
      the protein species even in highly enriched samples, such as culture filtrates.
      Only then the functional level of proteomics will be achieved and potential
      biomarkers can be postulated at the molecular level. BIOLOGICAL SIGNIFICANCE:
      Proteomics is dominated by bottom-up approaches largely ignoring protein
      speciation. A prerequisite to reach the protein species level is to obtain 100%
      sequence coverage, which is a major challenge in proteomics. Here we show
      complete sequence information with a 2-DE-MS approach for 15 protein species.
      Acetylation of the N-terminus of ESAT-6 inhibits interaction with CFP-10, with
      direct consequences for pathogen-host interaction. This article is part of a
      Special Issue entitled: Trends in Microbial Proteomics.

PMID- 23856609
TI  - Platelet-derived growth factor C promotes revascularization in ischemic limbs of
      diabetic mice.
AB  - BACKGROUND: Platelet-derived growth factor C (PDGF-C) has been reported to
      promote angiogenesis independently of vascular endothelial growth factor (VEGF),
      although its significance in postnatal angiogenesis in vivo remains poorly
      understood. VEGF has been employed as a major molecular tool to induce
      therapeutic angiogenesis. However, VEGF therapy is not very effective in models
      of cardiovascular diseases associated with diabetes, and the mechanisms of this
      phenomenon still remain to be elucidated. METHODS: We used a murine model of hind
      limb ischemia and of streptozotocin-induced diabetes. RESULTS: Expression of PDGF
      C and its receptor PDGFR-alpha were markedly upregulated in ischemic limbs.
      Treatment with a neutralizing antibody against PDGF-C significantly impaired
      blood flow recovery and neovascularization after ischemia almost to the same
      extent as a VEGF-neutralizing antibody. Mice deficient in PDGF-C exhibited
      reduced blood flow recovery after ischemia compared with wild-type mice,
      confirming a strong proangiogenic activity of PDGF-C. Next, we injected an
      expression vector encoding PDGF-C into ischemic limbs. Blood flow recovery and
      neovascularization after ischemia were significantly improved in the groups
      treated with PDGF-C compared with controls. Attenuation of angiogenic responses
      to ischemia has been reported in patients with diabetes even after VEGF
      treatment, although a precise mechanism remains unknown. We hypothesized that
      PDGF-C might relate to the impaired angiogenesis of diabetes. We tested this
      hypothesis by inducing diabetes by intraperitoneal injection of streptozotocin.
      Expression levels of PDGF-C at baseline and after ischemia were significantly
      lower in limb tissues of diabetic mice than in those of control mice, whereas
      expression levels of other members of the PDGF family and VEGF were not changed
      or were even higher in diabetic mice. Introduction of VEGF complementary DNA
      expression plasmid vector into ischemic limbs did not improve blood flow
      recovery. However, these changes were effectively reversed by additional
      introduction of the PDGF-C complementary DNA plasmid vector. CONCLUSIONS: These
      results indicate that downregulation of PDGF-C expression in limb tissues of
      diabetic mice contributes to impaired angiogenesis and suggest that introduction
      of PDGF-C might be a novel strategy for therapeutic angiogenesis, especially in
      the diabetic state. CLINICAL RELEVANCE: Angiogenesis and arteriogenesis after
      ischemia are attenuated in most diabetic patients, although the precise
      mechanisms remain unclear. Platelet-derived growth factors (PDGFs) have a variety
      of functions on many cell types, and PDGF-C stimulates angiogenesis and
      revascularizes ischemic tissues. This study indicates the role for PDGF-C as a
      critical regulator of impaired angiogenesis of diabetes and suggests that PDGF-C
      might be a novel target for the treatment of ischemic cardiovascular diseases in
      diabetes.

PMID- 23856611
TI  - Arteriovenous malformations: a diagnostic and therapeutic challenge.
AB  - Many dermatologists are largely unfamiliar with arteriovenous malformations
      (AVMs). This is partly due to the low prevalence of these lesions and to the fact
      that they are generally managed by other specialists, in particular,
      interventional radiologists and pediatric, maxillofacial, and plastic surgeons.
      In this article, we review the recommended nomenclature for AVMs and look at
      their clinical manifestations and diagnosis, as well as the ideal type and time
      of treatment. AVMs should be managed from a multidisciplinary approach, and the
      dermatologist's primary goal should be to make a proper diagnosis and thereby
      avoid unnecessary treatments. 

PMID- 23856610
TI  - Low levels of a natural IgM antibody are associated with vein graft stenosis and
      failure.
AB  - BACKGROUND: All humans have natural, protective antibodies directed against
      phosphorylcholine (PC) epitopes, a common inflammatory danger signal appearing at
      sites of cell injury, oxidative stress, and on bacterial capsules. In large human
      cohorts, low levels of anti-PC IgM were associated with a significantly increased
      risk of stroke or myocardial infarction. However, it is not known if these
      antibodies protect against the premature closure of arterial reconstructions.
      METHODS: A prospective, observational study of patients undergoing elective,
      infrainguinal, autogenous vein bypasses for atherosclerotic occlusive disease of
      the legs was conducted. Clinical data were recorded prospectively, and
      preoperative levels of anti-PC IgM measured with the CVDefine kit from Athera
      Biotechnologies (Solna, Sweden). The principal clinical end point was the loss of
      primary patency (loss of graft flow, or any intervention for stenosis). Patients
      were followed regularly by duplex ultrasound at 1, 3, 6, 12, 18 months, and
      yearly thereafter. RESULTS: Fifty-six patients were studied, for an average of
      1.3 years. Indications for surgery were claudication (33.9%), ischemic rest pain
      (17.9%), and ischemia with ulceration or gangrene (48.2%). Seventeen (30.4%)
      patients experienced loss of primary patency (10 graft occlusions, seven surgical
      or endovascular revisions of graft stenoses). Kaplan-Meier survival analysis
      showed that the quartile of patients with the lowest anti-PC IgM levels had
      significantly worse primary graft patency (log-rank test, P = .0085). Uni- and
      multivariate Cox proportional hazards analysis revealed that the preoperative
      anti-PC IgM level was an important predictor of graft failure. Patients with IgM
      values in the lowest quartile had a 3.6-fold increased risk of graft failure (95%
      confidence interval: 1.1-12.1), even after accounting for other significant
      clinical or technical factors such as indication for surgery, site of distal
      anastomosis, or vein graft diameter. CONCLUSIONS: A naturally occurring IgM
      antibody directed against the proinflammatory epitope PC may be protective
      against vein graft stenosis and failure, through anti-inflammatory mechanisms.
      Measurement of this antibody may be a useful prognostic indicator, although
      larger studies of more diverse populations will be needed to confirm these
      results. The biological actions of anti-PC IgM suggest it may be useful in
      developing immunotherapies to improve bypass longevity.

PMID- 23856612
TI  - Curcumin ameliorates dextran sulfate sodium-induced experimental colitis by
      blocking STAT3 signaling pathway.
AB  - BACKGROUND AND AIMS: Although a series of studies have shown that curcumin can
      exert anti-inflammatory effects in colitis by inhibiting NF-kappaB activation,
      whether these anti-inflammatory effects of curcumin are also attributed to its
      ability to inhibiting STAT3 pathway has never been tested in experimental colitis
      to date. The purpose of the study was to investigate whether curcumin could exert
      its therapeutic effects in experimental colitis by inhibiting STAT3 pathway.
      MATERIALS AND METHODS: Curcumin was administered in experimental colitis induced
      by dextran sulfate sodium (DSS). The disease activity index (DAI) and
      histological score were observed. The phospho-STAT3 was assessed by western blot
      analysis. The DNA-binding activity of STAT3 dimers was evaluated by
      electrophoretic mobility shift assay (EMSA). The expression of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta was measured by enzyme-linked
      immunosorbent assay. Myeloperoxidase (MPO) activity was determined by using MPO
      assay kit. RESULTS: A significant improvement was observed in DAI and
      histological score in mice with curcumin, and the increases in phospho-STAT3
      activity, DNA-binding activity of STAT3 dimers, MPO activity, IL-1beta, and TNF
      alpha expression in mice with DSS-induced colitis were significantly reduced
      following treatment with curcumin. CONCLUSION: Curcumin exerts beneficial effects
      in experimental colitis by the suppression of STAT3 pathway, which may therefore
      provide a better understanding of the mechanism of action for curcumin in
      treating colitis.

PMID- 23856613
TI  - The relationship between osteoprotegerin gene polymorphisms and bone mineral
      density in Chinese postmenopausal women.
AB  - Previous evidence supports that the osteoprotegerin (OPG) gene is one of the most
      important candidate genes for influencing the pathogenesis of osteoporosis. The
      objective of this study was to investigate the relationship between OPG gene
      polymorphisms and osteoporosis in Chinese postmenopausal women. A total of 764
      subjects were included in this study. The bone mineral density (BMD) in the
      lumbar spine (L2-4), neck hip and total hip was determined by dual-energy X-ray
      absorptiometry (DEXA). The g.19190C>A and g.25602A>G SNPs were detected by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),
      created restriction site PCR (CRS-PCR) and DNA sequencing methods. As for
      g.19190C>A, our data suggested that the BMD value of lumbar spine (L2-4), neck
      hip and total hip for subjects with CC genotype was significantly higher than
      that of CA and AA genotypes (P<0.05). No significant difference was detected
      between the association of g.25602A>G genotypes with spine BMD and neck hip BMD,
      while total hip BMD almost reached the significant level (P=0.063). These
      findings provide more evidence that the SNPs in OPG gene could affect BMD and
      osteoporosis, and the allele-A of g.19190C>A and allele-G of g.25602A>G genetic
      variants are associated with increased risk for osteoporosis in Chinese
      postmenopausal women. 

PMID- 23856614
TI  - Vorinostat, a HDAC inhibitor, showed anti-osteoarthritic activities through
      inhibition of iNOS and MMP expression, p38 and ERK phosphorylation and blocking
      NF-kappaB nuclear translocation.
AB  - Overproduction of nitric oxide (NO) and matrix metalloproteinases (MMPs) plays an
      important role in the pathogenesis of osteoarthritis (OA). In present study, we
      investigated whether vorinostat can inhibit the catabolic effects of IL-1beta in
      vitro, especially the inhibition of MMPs and inducible nitric oxide synthase
      (iNOS) through the attenuation of nuclear factor kappa-B (NF-kappaB) and mitogen
      activated protein kinase (MAPK) pathways in human chondrocytes. Human OA
      chondrocytes were either left untreated or treated with various concentrations of
      vorinostat followed by incubation with IL-1beta (5ng/mL). Effects of vorinostat
      on IL-1beta-induced gene and protein expression of iNOS, MMP-1, MMP-13 and tissue
      inhibitors of metalloproteinase-1 (TIMP-1) were verified by quantitative real
      time-PCR and Western blot analysis. Production of NO, MMP-1, MMP-13 and TIMP-1
      released in culture supernatant was estimated using commercially available kits.
      The roles of NF-kappaB and MAPK pathways in the regulation of targeted genes and
      the mechanism involved in vorinostat mediated modulation of these genes were
      determined by Western blot using specific antibodies. We found that vorinostat
      down-regulated iNOS, MMP-1 and MMP-13 expression and up-regulated TIMP-1
      expression in human OA chondrocytes. In addition, the release of NO, MMP-1 and
      MMP-13 secreted from IL-1beta stimulated chondrocytes was also suppressed by
      vorinostat. Interestingly, vorinostat selectively inhibited IL-1beta-induced p38
      and ERK1/2 activation without affecting JNK activation. Furthermore, we observed
      that vorinostat inhibited NF-kappaB pathway by suppressing the degradation of I
      kappaBalpha and attenuating NF-kappaB p65 translocation to the nucleus. These
      results suggest that vorinostat may be a promising therapeutic agent for the
      prevention and treatment of OA. 

PMID- 23856615
TI  - Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells.
AB  - Ultraviolet (UV) radiations present in sunlight are a major etiologic factor for
      many skin diseases and induce DNA damage through formation of cyclobutane
      pyrimidine dimer (CPD). This study was conducted to determine the toxicological
      effects of different wavelengths (250, 270, 290, and 310 nm) and doses of UV
      radiation on cell viability, DNA structure, and DNA damage repair mechanisms in a
      PC12 cell system. For this, we evaluated cell viability and CPD formation. Cell
      survival rate was markedly decreased 24h after UV irradiation in a dose-dependent
      manner at all wavelengths (except at 310 nm). Cell viability increased with
      increasing wavelength in the following order: 250<270<290<310 nm. UV radiation at
      250 nm showed the highest cell killing ability, with a median lethal dose (LD50)
      of 120 mJ/cm(2). The LD50 gradually increased with increase in wavelength. Among
      the 4 wavelengths tested, the highest LD50 (6000 mJ/cm(2)) was obtained for 310
      nm. CPD formation decreased substantially with increasing wavelength. Among the 4
      wavelengths, the proportion of CPD formation was highest at 250 nm and lowest at
      310 nm. On the basis of LD50 values for each wavelength, PC12 cells irradiated
      with UV radiation of 290 nm showed maximum DNA repair ability, whereas those
      irradiated with the 310-nm radiation did not show any repair ability. Toxicity of
      UV radiation varied with wavelengths and exposure doses.

PMID- 23856616
TI  - Spatial and temporal dynamics of neurite regrowth.
AB  - Injury to mature neurites triggers a series of events that have both growth
      promoting and inhibitory roles. Recent evidence from a variety of experimental
      models has revealed new neuronal re-growth modulators. The action of these
      modulators must be precisely regulated both in time and space, and involves
      multiple cellular processes including retrograde signaling and local translation
      in the injured neurite. New genetic techniques, in combination with
      pharmacological approaches, have served to advance mechanistic dissection of
      neuronal response to injury. Better understanding of the spatio-temporal cues
      would greatly aid in the development of effective regenerative therapies. 

PMID- 23856617
TI  - Reality mining of animal social systems.
AB  - The increasing miniaturisation of animal-tracking technology has made it possible
      to gather exceptionally detailed machine-sensed data on the social dynamics of
      almost entire populations of individuals, in both terrestrial and aquatic study
      systems. Here, we review important issues concerning the collection of such data,
      and their processing and analysis, to identify the most promising approaches in
      the emerging field of 'reality mining'. Automated technologies can provide data
      sensing at time intervals small enough to close the gap between social patterns
      and their underlying processes, providing insights into how social structures
      arise and change dynamically over different timescales. Especially in conjunction
      with experimental manipulations, reality mining promises significant advances in
      basic and applied research on animal social systems. 

PMID- 23856618
TI  - Matrix metalloproteinases 2 and 9 are differentially expressed in patients with
      indeterminate and cardiac clinical forms of Chagas disease.
AB  - Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with
      myocardial remodeling and interstitial fibrosis, resulting in extracellular
      matrix (ECM) changes. In this study, we characterized for the first time the
      serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main
      cell sources in peripheral blood mononuclear cells from patients presenting with
      the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our
      results showed that serum levels of MMP-9 are associated with the severity of
      Chagas disease. The analysis of MMP production by T lymphocytes showed that
      CD8(+) T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9
      molecules. Using a new 3-dimensional model of fibrosis, we observed that sera
      from patients with Chagas disease induced an increase in the extracellular matrix
      components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different
      correlations with matrix proteins and inflammatory cytokines in patients with
      Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities
      in Chagas disease pathogenesis. While MMP-9 seems to be involved in the
      inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate
      with inflammatory molecules. 

PMID- 23856619
TI  - Transcriptome analysis of mouse brain infected with Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular parasite that invades a wide range
      of vertebrate host cells. Chronic infections with T. gondii become established in
      the tissues of the central nervous system, where the parasites may directly or
      indirectly modulate neuronal function. However, the mechanisms underlying
      parasite-induced neuronal disorder in the brain remain unclear. This study
      evaluated host gene expression in mouse brain following infection with T. gondii.
      BALB/c mice were infected with the PLK strain, and after 32 days of infection,
      histopathological lesions in the frontal lobe were found to be more severe than
      in other areas of the brain. Total RNA extracted from infected and uninfected
      mouse brain samples was subjected to transcriptome analysis using RNA sequencing
      (RNA-seq). In the T. gondii-infected mice, 935 mouse brain genes were
      upregulated, whereas 12 genes were downregulated. GOstat analysis predicted that
      the upregulated genes were primarily involved in host immune responses and cell
      activation. Positive correlations were found between the numbers of parasites in
      the infected mouse brains and the expression levels of genes involved in host
      immune responses. In contrast, genes that had a negative correlation with
      parasite numbers were predicted to be involved in neurological functions, such as
      small-GTPase-mediated signal transduction and vesicle-mediated transport.
      Furthermore, differential gene expression was observed between mice exhibiting
      the clinical signs of toxoplasmosis and those that did not. Our findings may
      provide insights into the mechanisms underlying neurological changes during T.
      gondii infection. 

PMID- 23856620
TI  - The structure of the cytochrome p450cam-putidaredoxin complex determined by
      paramagnetic NMR spectroscopy and crystallography.
AB  - Cytochrome P450cam catalyzes the hydroxylation of camphor in a complex process
      involving two electron transfers (ETs) from the iron-sulfur protein
      putidaredoxin. The enzymatic control of the successive steps of catalysis is
      critical for a highly efficient reaction. The injection of the successive
      electrons is part of the control system. To understand the molecular interactions
      between putidaredoxin and cytochrome P450cam, we determined the structure of the
      complex both in solution and in the crystal state. Paramagnetic NMR spectroscopy
      using lanthanide tags yielded 446 structural restraints that were used to
      determine the solution structure. An ensemble of 10 structures with an RMSD of
      1.3A was obtained. The crystal structure of the complex was solved, showing a
      position of putidaredoxin that is identical with the one in the solution
      structure. The NMR data further demonstrate the presence of a minor state or set
      of states of the complex in solution, which is attributed to the presence of an
      encounter complex. The structure of the major state shows a small binding
      interface and a metal-to-metal distance of 16A, with two pathways that provide
      strong electronic coupling of the redox centers. The interpretation of these
      results is discussed in the context of ET. The structure indicates that the ET
      rate can be much faster than the reported value, suggesting that the process may
      be gated. 

PMID- 23856621
TI  - Advances in molecular modeling of human cytochrome P450 polymorphism.
AB  - Cytochrome P450 (CYP) is a supergene family of metabolizing enzymes involved in
      the phase I metabolism of drugs and endogenous compounds. CYP oxidation often
      leads to inactive drug metabolites or to highly toxic or carcinogenic metabolites
      involved in adverse drug reactions (ADR). During the last decade, the impact of
      CYP polymorphism in various drug responses and ADR has been demonstrated. Of the
      drugs involved in ADR, 56% are metabolized by polymorphic phase I metabolizing
      enzymes, 86% among them being CYP. Here, we review the major CYP polymorphic
      forms, their impact for drug response and current advances in molecular modeling
      of CYP polymorphism. We focus on recent studies exploring CYP polymorphism
      performed by the use of sequence-based and/or protein-structure-based
      computational approaches. The importance of understanding the molecular
      mechanisms related to CYP polymorphism and drug response at the atomic level is
      outlined. 

PMID- 23856622
TI  - Structures of intermediates along the catalytic cycle of terminal
      deoxynucleotidyltransferase: dynamical aspects of the two-metal ion mechanism.
AB  - Terminal deoxynucleotidyltransferase (Tdt) is a non-templated eukaryotic DNA
      polymerase of the polX family that is responsible for the random addition of
      nucleotides at the V(D)J junctions of immunoglobulins and T-cell receptors. Here
      we describe a series of high-resolution X-ray structures that mimic the pre
      catalytic state, the post-catalytic state and a competent state that can be
      transformed into the two other ones in crystallo via the addition of dAMPcPP and
      Zn(2+), respectively. We examined the effect of Mn(2+), Co(2+) and Zn(2+) because
      they all have a marked influence on the kinetics of the reaction. We demonstrate
      a dynamic role of divalent transition metal ions bound to site A: (i) Zn(2+) (or
      Co(2+)) in Metal A site changes coordination from octahedral to tetrahedral after
      the chemical step, which explains the known higher affinity of Tdt for the primer
      strand when these ions are present, and (ii) metal A has to leave to allow the
      translocation of the primer strand and to clear the active site, a typical
      feature for a ratchet-like mechanism. Except for Zn(2+), the sugar puckering of
      the primer strand 3' terminus changes from C2'-endo to C3'-endo during catalysis.
      In addition, our data are compatible with a scheme where metal A is the last
      component that binds to the active site to complete its productive assembly, as
      already inferred in human pol beta. The new structures have potential
      implications for modeling pol mu, a closely related polX implicated in the repair
      of DNA double-strand breaks, in a complex with a DNA synapsis. 

PMID- 23856623
TI  - Nuclear Respiratory Factor 2beta (NRF-2beta) recruits NRF-2alpha to the nucleus
      by binding to importin-alpha:beta via an unusual monopartite-type nuclear
      localization signal.
AB  - Nuclear respiratory factor 2 (NRF-2) is a mammalian transcription factor composed
      of two distinct and unrelated proteins: NRF-2alpha, which binds to DNA through
      its Ets domain, and NRF-2beta, which contains the transcription activation
      domain. The activity of NRF-2 in neurons is regulated by nuclear localization;
      however, the mechanism by which NRF-2 is imported into the nucleus remains
      unknown. By using in vitro nuclear import assays and immuno-cytofluorescence, we
      dissect the nuclear import pathways of NRF-2. We show that both NRF-2alpha and
      NRF-2beta contain intrinsic nuclear localization signals (NLSs): the Ets domain
      within NRF-2alpha and the NLS within NRF-2beta (amino acids 311/321: EEPPAKRQCIE)
      that is recognized by importin-alpha:beta. When NRF-2alpha and NRF-2beta form a
      complex, the nuclear import of NRF-2alphabeta becomes strictly dependent on the
      NLS within NRF-2beta. Therefore, the nuclear import mechanism of NRF-2 is unique
      among Ets factors. The NRF-2beta NLS contains only two lysine/arginine residues,
      unlike other known importin-alpha:beta-dependent NLSs. Using ELISA-based binding
      assays, we show that it is bound by importin-alpha in almost the same manner and
      with similar affinity to that of the classical monopartite NLSs, such as c-myc
      and SV40 T-antigen NLSs. However, the part of the tryptophan array of importin
      alpha that is essential for the recognition of classical monopartite NLSs by
      generating apolar pockets for the P3 and the P5 lysine/arginine side chains is
      not required for the recognition of the NRF-2beta NLS. We conclude that the NRF
      2beta NLS is an unusual but is, nevertheless, a bona fide monopartite-type NLS. 

PMID- 23856624
TI  - HIV-1 maternal and infant variants show similar sensitivity to broadly
      neutralizing antibodies, but sensitivity varies by subtype.
AB  - RATIONALE: To protect against HIV infection, passively transferred and/or vaccine
      elicited neutralizing antibodies (NAbs) need to effectively target diverse
      subtypes that are transmitted globally. These variants are a limited subset of
      those present during chronic infection and display some unique features. In the
      case of mother-to-child transmission (MTCT), transmitted variants tend to be
      resistant to neutralization by maternal autologous NAbs. METHOD: To investigate
      whether variants transmitted during MTCT are generally resistant to HIV-1
      specific NAbs, 107 maternal or infant variants representing the dominant HIV-1
      subtypes were tested against six recently identified HIV-1-specific broadly
      neutralizing monoclonal antibodies (bNAbs), NIH45-46W, VRC01, PGT128, PGT121, PG9
      and PGT145. RESULTS: Infant and maternal variants did not differ in their
      neutralization sensitivity to individual bNAbs, nor did viruses from transmitting
      versus nontransmitting mothers, although there was a trend for viruses from
      transmitting mothers to be less sensitive overall. No single bNAb neutralized all
      viruses, but a combination of bNAbs that target distinct epitopes covered 100% of
      the variants tested. Compared with heterosexually transmitted variants,
      vertically transmitted variants were significantly more sensitive to
      neutralization by PGT128 and PGT121 (P=0.03 in both cases), but there were no
      differences for the other bNAbs. Overall, subtype A variants were significantly
      more sensitive to NIH45-46 (P=0.04), VRC01 (P=0.002) and PGT145 (P=0.03) compared
      with the nonsubtype A and less sensitive to PGT121 than subtype Cs (P=0.0001).
      CONCLUSION: A combination of bNAbs against distinct epitopes may be needed to
      provide maximum coverage against viruses in different modes of transmission and
      diverse subtypes.

PMID- 23856625
TI  - The role of subtotal petrosectomy in cochlear implant surgery--a report of 32
      cases and review on indications.
AB  - OBJECTIVE: To report and review 32 cases of subtotal petrosectomy (SP) in
      cochlear implant (CI) surgery and to define the indications and contraindications
      for this procedure. STUDY DESIGN: Retrospective case review + case reports.
      SETTING: Tertiary skull base center. PATIENTS: Cochlear implant database: 32
      subtotal petrosectomies in 31 patients. INTERVENTIONS: Subtotal petrosectomy with
      blind sac closure of the external auditory canal, closure of Eustachian tube, and
      abdominal fat obliteration in combination with cochlear implantation. RESULTS:
      Indications for SP in CI surgery were as follows: chronic otitis media (n = 4),
      previous radical cavity (n = 13), previous subtotal petrosectomy (n = 4),
      ossification of the cochlea (n = 5), malformation of the inner ear (n = 2), and
      temporal bone fracture (n = 4). One patient was simultaneously bilaterally
      implanted; 2 cases were revisions. All procedures were performed in 1 stage. In 2
      cases, complications were encountered (6%), one of which lead to reoperation
      (3%). None of the patients was explanted. CONCLUSION: Subtotal petrosectomy
      combined with cochlear implantation is a procedure required in specific
      situations and lowers the risk of repetitive ear infections, CSF leakage, and
      meningitis by closing off all connection with the external environment.
      Additionally, it gives excellent visibility and access in difficult anatomy or in
      drill-out procedures. The complication rate of 6% is comparable with normal
      cochlear implantation. Preservation of residual hearing can be considered the
      only absolute contraindication as an open external meatus is necessary for use of
      electroacoustic stimulation. Risks of the SP+CI procedure are infection of the
      abdominal fat, breakdown of the blind sac closure, and entrapped cholesteatoma.
      Follow-up with CT imaging is therefore mandatory.

PMID- 23856626
TI  - Comparison of speech discrimination in noise and directional hearing with 2
      different sound processors of a bone-anchored hearing system in adults with
      unilateral severe or profound sensorineural hearing loss.
AB  - OBJECTIVE: To evaluate and compare the benefit of a bone-anchored hearing implant
      with 2 different sound processors in adult patients with unilateral severe to
      profound sensorineural hearing loss (UHL). STUDY DESIGN: Prospective crossover
      design. SETTING: Tertiary referral center. PATIENTS: Eleven adults with UHL and
      normal hearing in the contralateral ear were assigned to 2 groups. INTERVENTION:
      All subjects were unilaterally implanted with a bone-anchored hearing implant and
      were initially fitted with 2 different sound processors (SP-1 and SP-2). SP-1 is
      a multichannel device equipped with an omnidirectional microphone and relatively
      simple digital signal-processing technology and provides a user-adjustable
      overall gain and tone control with compression limiting. SP-2 is a fully channel
      by-channel programmable device, which can be set with nonlinear dynamic range
      compression or linear amplification. In addition, SP-2 features automatic noise
      management, an automatic multichannel directional microphone, microphone position
      compensation, and an implementation of prescription rules for different types of
      hearing losses, one of them unilateral deafness. After at least 1-month use of
      the initial processor, both groups were fitted with the alternative processor.
      MAIN OUTCOME MEASURES: Speech discrimination in noise and localization tests were
      performed at baseline visit before surgery, after at least 1-month use of the
      initial processor, and after at least 2-week use of the alternative processor.
      RESULTS: Relative to unaided baseline, SP-2 enabled significantly better overall
      speech discrimination results, whereas there was no overall improvement with SP
      1. There was no difference in speech discrimination between SP-1 and SP-2 in all
      spatial settings. Sound localization was comparably poor at baseline and with
      both processors but significantly better than chance level for all 3 conditions.
      CONCLUSION: Patients with UHL have an overall objective benefit for speech
      discrimination in noise using a bone-anchored hearing implant with SP-2. In
      contrast, there is no overall objective benefit from SP-1. Depending on the
      speech-in-noise presentation setting, the difference between objective benefit
      from SP-2 and SP-1 might be mainly attributed to the new technological features
      in SP-2 unavailable in SP-1 such as 1) automatic noise management reducing the
      noise in the speech signal and thus improving the signal-to-noise ratio of the
      resulting signal on the better ear, 2) programmable multichannel sound-processing
      and nonlinear dynamic range compression offering considerably greater control
      over signal amplification compared to SP-1, and 3) implementation of a
      prescription rule for unilateral deafness addressing the specific amplification
      needs of patients with UHL by reducing amplification in the low frequencies and
      applying additional gain in the high frequencies. Sound localization is poor but
      better than chance level in the unaided condition as well as in both bone
      anchored hearing system-aided conditions.

PMID- 23856627
TI  - Therapeutic implications of biomarkers in chronic heart failure.
AB  - Understanding of chronic heart failure (HF) has progressed from the concept of a
      purely hemodynamic disorder to that of a syndrome that results from dysfunction
      in interconnected molecular pathways. As a result, the focus of research
      investigations and clinical care has shifted to measurement and modification of
      maladaptive molecular processes. Accumulating evidence shows that molecular
      biomarkers provide a window into the pathophysiology of chronic HF and therefore
      have important therapeutic implications. However, the use of biomarkers in the
      treatment of HF remains in its infancy. This is partly a result of shortcomings
      in research studies and a dearth of biomarker-guided clinical trials. In this
      review, we summarize the potential therapeutic implications of promising
      biomarkers that uniquely capture the molecular dysfunction that occurs in chronic
      HF. We discuss the need for strict statistical standards in biomarker studies,
      provide an overview of biomarker-guided clinical trial design, and discuss the
      therapeutic potential of a multimarker-based strategy.

PMID- 23856628
TI  - Inhibition and impulsivity: behavioral and neural basis of response control.
AB  - In many circumstances alternative courses of action and thoughts have to be
      inhibited to allow the emergence of goal-directed behavior. However, this has not
      been the accepted view in the past and only recently has inhibition earned its
      own place in the neurosciences as a fundamental cognitive function. In this
      review we first introduce the concept of inhibition from early psychological
      speculations based on philosophical theories of the human mind. The broad
      construct of inhibition is then reduced to its most readily observable component
      which necessarily is its behavioral manifestation. The study of 'response
      inhibition' has the advantage of dealing with a relatively simple and
      straightforward process, the overriding of a planned or already initiated action.
      Deficient inhibitory processes profoundly affect everyday life, causing impulsive
      conduct which is generally detrimental for the individual. Impulsivity has been
      consistently linked to several types of addiction, attention
      deficit/hyperactivity disorder, mania and other psychiatric conditions. Our
      discussion of the behavioral assessment of impulsivity will focus on objective
      laboratory tasks of response inhibition that have been implemented in parallel
      for humans and other species with relatively few qualitative differences. The
      translational potential of these measures has greatly improved our knowledge of
      the neurobiological basis of behavioral inhibition and impulsivity. We will then
      review the current models of behavioral inhibition along with their expression
      via underlying brain regions, including those involved in the activation of the
      brain's emergency 'brake' operation, those engaged in more controlled and
      sustained inhibitory processes and other ancillary executive functions. 

PMID- 23856629
TI  - Intersphinteric resection for rectal cancer: role in fecal continence and Quality
      of Life.
AB  - AIM: Aim of this study is to evaluate the presence of fecal incontince and its
      impact on life-quality after intersphincteric resection for low rectal cancer.
      MATERIAL AND METHODS: Twentyeight patients (18 males and 10 female) underwent
      intersphincteric resection for low rectal cancer between 2006 and 2008. The
      presence of fecal incontinence was evaluated by Wexner score pre-operatory and 3,
      6 and 12 months after ileostomy closure; Quality of Life was evaluated by Fecal
      Incontinence Quality Of Life (FIQL) score. RESULTS: Wexner score was
      significatively (p<0.01) higher in the post-operative period (14,07 +/- 1.94,
      13.36 +/- 2.3 and 12.29 +/- 2.3 at 3.6 and 12 months) than the pre-operative one
      (0.72 +/- 0.71). Post-operative life-quality specifically related to fecal
      incontince was worse than in the pre-operative period (FIQL: 10.84 +/- 2.52 at 12
      months vs 16 preoperative period). DISCUSSION: Wexner score results show a
      significative worsening in fecal incontinence after intersphincteric resection,
      even if this condition seems to improve during the follow-up. These results agree
      with literature. CONCLUSIONS: Intersphincteric resection for low rectal cancer is
      associated, in the short term (12 months), with a significative state of fecal
      incontinence. This state has a significative impact on life-quality. However a
      longer follow-up probably might show an improvement in life-quality parameters.

PMID- 23856630
TI  - The J-wave: a new electrocardiographic sign of an occult cardiac injury.
AB  - BACKGROUND: The aim of this study was to determine the sensitivity and
      specificity of a J wave on the electrocardiogram (ECG) to detect an occult
      cardiac injury in patients following penetrating chest trauma. METHOD: A
      prospective study conducted on patients admitted to the Groote Schuur Hospital
      Trauma Centre following penetrating chest trauma during the period of 1st October
      2001 and 28th February 2009, who did not have an indication for emergency surgery
      and that underwent an ECG and later a subxiphoid pericardial window (SPW) for a
      potential cardiac injury. All the patients were easily resuscitatable with less
      than 2l of crystalloid. A standard 12-lead ECG was performed shortly after
      admission. A J wave was defined as the small positive reflection on the R-ST
      junction. RESULTS: There were 174 patients where an ECG was performed and the
      patient underwent SPW for a possible cardiac injury. The mean age of the patients
      was 28 years (range 11-65). The mechanism of injury was stab wounds in 167
      patients and 7 low velocity gunshot wounds. A J-wave was present on the ECG in 65
      (37%) of the 174 patients with a possible cardiac injury. The sensitivity of a J
      wave to detect a hemopericardium was 44%, specificity was 85%, and positive
      predictive value of 91% (p<0.001). CONCLUSION: The presence of a 'J' wave on ECG
      signifies a significant risk of an occult cardiac injury after penetrating
      thoracic trauma.

PMID- 23856631
TI  - In hypothermic major trauma patients the appropriate hospital for damage control
      and rewarming may be life saving.

PMID- 23856632
TI  - Safe cervical spine clearance in adult obtunded blunt trauma patients on the
      basis of a normal multidetector CT scan--a meta-analysis and cohort study.
AB  - BACKGROUND: A true gold standard to rule out a significant cervical spine injury
      in subset of blunt trauma patients with altered sensorium is still to be agreed
      upon. The objective of this study is to determine whether in obtunded adult
      patients with blunt trauma, a clinically significant injury to the cervical spine
      be ruled out on the basis of a normal multidetector cervical spine computed
      tomography. METHODS: Comprehensive database search was conducted to include all
      the prospective and retrospective studies on blunt trauma patients with altered
      sensorium undergoing cervical spine multidetector CT scan as core imaging
      modality to "clear" the cervical spine. The studies used two main gold standards,
      magnetic resonance imaging of the cervical spine and/or prolonged clinical follow
      up. The data was extracted to report true positive, true negatives, false
      positives and false negatives. Meta-analysis of sensitivity, specificity,
      negative and positive predictive values was performed using Meta Analyst Beta
      3.13 software. We also performed a retrospective investigation comparing a robust
      clinical follow-up and/or cervical spine MR findings in 53 obtunded blunt trauma
      patients, who previously had undergone a normal multidetector CT scan of the
      cervical spine reported by a radiologist. RESULTS: A total of 10 studies
      involving 1850 obtunded blunt trauma patients with initial cervical spine CT scan
      reported as normal were included in the final meta-analysis. The cumulative
      negative predictive value and specificity of cervical spine CT of the ten studies
      was 99.7% (99.4-99.9%, 95% confidence interval). The positive predictive value
      and sensitivity was 93.7% (84.0-97.7%, 95% confidence interval). In the
      retrospective review of our obtunded blunt trauma patients, none was later
      diagnosed to have significant cervical spine injury that required a change in
      clinical management. CONCLUSION: In a blunt trauma patient with altered
      sensorium, a normal cervical spine CT scan is conclusive to safely rule out a
      clinically significant cervical spine injury. The results of this meta-analysis
      strongly support the removal of cervical precautions in obtunded blunt trauma
      patient after normal cervical spine computed tomography. Any further imaging like
      magnetic resonance imaging of the cervical spine should be performed on case-to
      case basis.

PMID- 23856633
TI  - Shall all congenital cystic lung malformations be removed? the case in favour.
AB  - The need to systematically remove congenital cystic lung lesions is based on
      three main arguments. First, cystic malformations are often considered as
      congenital cystic adenomatoid malformations (CCAM), while other less favorable
      diagnoses are possible, such as pleuropulmonary blastoma. Only postsurgical
      pathological analysis allows diagnosis. Second, there are clinical and biological
      arguments for considering macrocystic lesions as likely to degenerate. The only
      prevention is surgical removal. Finally, there is no recommendation on how to
      follow these children, in the absence of removal, causing unnecessary family
      stress. This seems unjustified, compared to a feasibility of thoracoscopic
      removal in most cases. 

PMID- 23856635
TI  - A plasmonic based ultracompact polarization beam splitter on silicon-on-insulator
      waveguides.
AB  - An ultracompact polarization beam splitter (PBS) is designed on silicon-on
      insulator (SOI) platform based on the localized surface plasmons (LSPs) excited
      by particular polarization light. The device uses nanoscale silver cylinders as
      the polarization selection between two silicon waveguides of a directional
      coupler. The transverse-magnetic (TM) polarization light excites localized
      surface plasmons and is coupled into the cross port of the directional coupler
      with a low insert loss, while the transverse-electric (TE) polarization light is
      under restriction. The PBS has a coupling layer with 50 nm width and 1.1 MUm
      length supporting broadband operation. The simulation calculations show that
      22.06dB and 23.06dB of extinction ratios for the TE and TM polarizations were
      obtained, together with insertion losses of 0.09dB and 0.40dB.

PMID- 23856634
TI  - The impact of NMDA receptor blockade on human working memory-related prefrontal
      function and connectivity.
AB  - Preclinical research suggests that N-methyl-D-aspartate glutamate receptors (NMDA
      Rs) have a crucial role in working memory (WM). In this study, we investigated
      the role of NMDA-Rs in the brain activation and connectivity that subserve WM.
      Because of its importance in WM, the lateral prefrontal cortex, particularly the
      dorsolateral prefrontal cortex and its connections, were the focus of analyses.
      Healthy participants (n=22) participated in a single functional magnetic
      resonance imaging session. They received saline and then the NMDA-R antagonist
      ketamine while performing a spatial WM task. Time-course analysis was used to
      compare lateral prefrontal activation during saline and ketamine administration.
      Seed-based functional connectivity analysis was used to compare dorsolateral
      prefrontal connectivity during the two conditions and global-based connectivity
      was used to test for laterality in these effects. Ketamine reduced accuracy on
      the spatial WM task and brain activation during the encoding and early
      maintenance (EEM) period of task trials. Decrements in task-related activation
      during EEM were related to performance deficits. Ketamine reduced connectivity in
      the DPFC network bilaterally, and region-specific reductions in connectivity were
      related to performance. These results support the hypothesis that NMDA-Rs are
      critical for WM. The knowledge gained may be helpful in understanding disorders
      that might involve glutamatergic deficits such as schizophrenia and developing
      better treatments. 

PMID- 23856636
TI  - A comparison of two validated scores for estimating risk of mortality of children
      with intestinal failure associated liver disease and those with liver disease
      awaiting transplantation.
AB  - BACKGROUND AND AIMS: To evaluate risk of mortality in children with intestinal
      failure associated liver disease (IFALD) compared with other liver disease using
      two validated scores. METHODS: Sixty-seven children listed for transplant were
      studied: cholestatic liver disease (CLDn23); liver disease secondary to other
      processes (LDsec n11); (IFALDn22), acute liver failure (ALFn11). Paediatric
      Hepatology Score (PHD) score and Pediatric end-stage liver disease score (PELD)
      were evaluated by Receiver Operating Curves (ROC), proportional hazards
      regression. RESULTS: The highest PHD and PELD scores were found in ALF; the
      lowest in LDsec. Both scores correlated well in identifying waiting list (WL)
      mortality in patients with CLD and ALF, but not in those with IFALD where PELD
      scores were lower. Cox proportional hazard regression of time spent on the
      waiting list prior to death or transplant/delisting showed significant
      associations with PHD (P=0.006) and PELD (P=0.008). WL mortality was strongly
      predicted by disease group (6/8 deaths in IFALD). ROC analysis of all data showed
      that a PHD score greater than 15.5 had sensitivity of 87.5% and specificity of
      81% for waiting list mortality (P<0.001); PELD greater than 8 had a sensitivity
      of 87.5% and specificity of 40%. Neither PHD nor PELD scores correlated with post
      transplant mortality. CONCLUSION: PHD and PELD scores had the same sensitivity
      for identifying risk of WL mortality in all patients, but PELD failed to identify
      the sickest children with IFALD, lowering its specificity. The PHD score has the
      added advantage for European centres of being in SI units, not requiring a
      computer application to calculate and was simpler to use at bedside.

PMID- 23856637
TI  - One-step circumferential endoscopic mucosal cap resection of Barrett's esophagus
      with early neoplasia.
AB  - BACKGROUND AND OBJECTIVE: Focal endoscopic mucosal resection (EMR) of visible
      intraepithelial lesions arising within Barrett's esophagus (BE) may miss
      synchronous lesions that are not endoscopically apparent. Stepwise radical
      endoscopic resection would obviate this concern by removing all BE; however, it
      requires repeated endoscopy which may increase the risk of complications,
      particularly for patients with circumferential BE. The aim of the study was to
      evaluate the safety and efficacy of one-step complete circumferential resection
      of BE by cap-assisted EMR (EMR-C) among patients with circumferential BE and high
      grade dysplasia or intramucosal carcinoma. PATIENTS AND METHODS: Between January
      2003 and March 2010, 47 patients with circumferential BE and biopsy-proven high
      grade dysplasia or intramucosal cancer underwent EMR-C. We evaluated: (1)
      complete eradication of neoplasia, (2) complete eradication of metaplasia, and
      (3) complications including bleeding and esophageal stricture. RESULTS: Complete
      eradication of neoplasia and complete eradication of metaplasia were achieved
      after a median follow-up of 18.4 months in 91% (43/47) of patients. After EMR-C,
      two patients (one IMC, one invasive cancer) underwent esophagectomy. Histology of
      the resected specimens showed no residual disease and a T1bN0 lesion,
      respectively. Two patients had progression of neoplasia. A stenosis occurred in
      18 out of 45 patients (40%). All stenoses were treated with dilations and two
      required temporary placement of a covered stent. CONCLUSION: One-step complete
      EMR-C is a safe and effective technique which can be considered in patients with
      early neoplastic lesions. Although 40% of patients developed dysphagia, this
      could well be managed endoscopically.

PMID- 23856638
TI  - Effects of estrogen on neuronal KCNQ2/3 channels expressed in PC-12 cells.
AB  - We previously reported that 17beta-estradiol (E2) improves long term potentiation
      (LTP) in hippocampal neurons after global ischemia in rat. In the present study,
      we investigated if E2 can directly modulate the activity of neuronal KCNQ2/3
      channels, the molecular entity of neuronal M-current in hippocampus, expressed in
      the PC-12 cells. We found that exogenous E2 inhibits the KCNQ2/3 channels in a
      dose-dependent fashion. The minimal inhibitory concentration of E2 is 10 uM. At
      testing membrane potential of +90 mV, the whole cell current density was reduced
      to 56.5, 49.3 and 31.9% of the control by 50, 20 and 10 uM of E2, respectively.
      The voltage-dependency of the KCNQ2/3 currents was also affected. E2 at 10, 20
      and 50 uM shifted the half maximal activation voltage (V1/2) from 13.8 +/- 2.3 mV
      (n=12) to 20.6 +/- 1.9 mV (n=8, p<0.05), 26.0 +/- 1.9 mV (n=8, p<0.001) and 27.6
      +/- 3.5 mV (n=8, p<0.001), respectively. Our data indicate that exogenous E2 can
      directly affect the activity of KCNQ2/3 channels at pharmacological levels via a
      non-genomic pathway.

PMID- 23856639
TI  - Immunoglobulin superfamily protein Dscam exhibited molecular diversity by
      alternative splicing in hemocytes of crustacean, Eriocheir sinensis.
AB  - Be absent of adaptive immunity which have both specificity and memory,
      invertebrates seem to have evolved alternative adaptive immune strategies to
      resist various intruding pathogens. Whereas vertebrates could generate a wide
      range of immunological receptors with somatic rearrangement, invertebrates
      possibly depend on alternative splicing of pattern-recognition receptors (PRRs).
      Recently, it has been suggested that a member of the immunoglobulin superfamily
      (IgSF), Down syndrome cell adhesion molecule (Dscam), plays a crucial role in the
      alternative adaptive immune system of invertebrates. At present, we successfully
      isolated and characterized the first crab Dscam from Eriocheir sinensis. EsDscam
      has typical domain architecture compared with other Dscam orthologs, including
      one signal-peptide, 10 immunoglobulin (Ig) domains, 6 fibronectin type III
      domains (FNIII), one transmembrane domain (TM) and one cytoplasmic tail. We had
      detected four hypervariable regions of EsDscam in the N-terminal halves of Ig2
      (25) and Ig3 domain (30), the complete Ig7 (18) and also the transmembrane domain
      (2), potentially generate 27,000 unique isoforms at least. Transcription of
      EsDscam were both a) detected in all tissues, especially in immune system,
      digestive system and nerve system; b) significantly induced in hemocytes post
      lipopolysaccharides (LPS), peptidoglycans (PG) and beta-1, 3-glucans (Glu)
      injection. Importantly, we had detected membrane-bound and secreted Dscam
      isoforms in E. sinensis, and showed that secreted isoforms were extensively
      transcribed post different PAMPs challenge respectively. Results from immuno
      localization assay revealed that EsDscam evenly distributed in the cell surface
      of hemocytes. These findings indicated that EsDscam is a hypervariable PRR in the
      innate immune system of the E. sinensis.

PMID- 23856640
TI  - The effect of the learner license Graduated Driver Licensing components on teen
      drivers' crashes.
AB  - BACKGROUND: Most studies evaluating the effectiveness of Graduated Driver
      Licensing (GDL) have focused on the overall system. Studies examining individual
      components have rarely accounted for the confounding of multiple, simultaneously
      implemented components. The purpose of this paper is to quantify the effects of a
      required learner license duration and required hours of supervised driving on
      teen driver fatal crashes. METHODS: States that introduced a single GDL component
      independent of any other during the period 1990-2009 were identified. Monthly and
      quarterly fatal crash rates per 100,000 population of 16- and 17-year-old drivers
      were analyzed using single-state time series analysis, adjusting for adult crash
      rates and gasoline prices. Using the parameter estimates from each state's time
      series model, the pooled effect of each GDL component on 16- and 17-year-old
      drivers' fatal crashes was estimated using a random effects meta-analytic model
      to combine findings across states. RESULTS: In three states, a six-month minimum
      learner license duration was associated with a significant decline in combined 16
      and 17-year-old drivers' fatal crash rates. The pooled effect of the minimum
      learner license duration across all states in the sample was associated with a
      significant change in combined 16- and 17-year-old driver fatal crash rates of 
      .07 (95% Confidence Interval [CI] -.11, -.03). Following the introduction of 30 h
      of required supervised driving in one state, novice drivers' fatal crash rates
      increased 35%. The pooled effect across all states in the study sample of having
      a supervised driving hour requirement was not significantly different from zero
      (.04, 95% CI -.15, .22). CONCLUSION: These findings suggest that a learner
      license duration of at least six-months may be necessary to achieve a significant
      decline in teen drivers' fatal crash rates. Evidence of the effect of required
      hours of supervised driving on teen drivers' fatal crash rates was mixed.

PMID- 23856641
TI  - Do lower income areas have more pedestrian casualties?
AB  - Pedestrian and motor vehicle casualties are analyzed for the State of New Jersey
      with the objective of determining how the income of an area may be associated
      with casualties. We develop a maximum-likelihood negative binomial model to
      examine how various spatially defined variables, including road, income, and
      vehicle ownership, may be associated with casualties using census block-group
      level data. Due to suspected spatial correlation in the data we also employ a
      conditional autoregressive Bayesian model using Markov Chain Monte Carlo
      simulation, implemented with Crimestat software. Results suggest that spatial
      correlation is an issue as some variables are not statistically significant in
      the spatial model. We find that both pedestrian and motor vehicle casualties are
      greater in lower income block groups. Both are also associated with less
      household vehicle ownership, which is not surprising for pedestrian casualties,
      but is a surprising result for motor vehicle casualties. Controls for various
      road categories provide expected relationships. Individual level data is further
      examined to determine relationships between the location of a crash victim and
      their residence zip code, and this largely confirms a residual effect associated
      with both lower income individuals and lower income areas. 

PMID- 23856642
TI  - Design, synthesis, and diversification of ribosomally derived peptide
      macrocycles.
AB  - Ring topologies are widespread structural motifs among biologically active
      peptides found in nature. The recurrence of this motif is linked to the inherent
      advantages resulting from backbone cyclization, which include increased
      resistance against proteolytic degradation, improved cell permeability, and
      tighter and more specific interaction with the respective biomolecular target.
      Inspired by these natural product topologies, a number of groups have recently
      focused on developing methodologies that hinge upon the chemical elaboration of
      ribosomally derived polypeptides toward the synthesis and diversification of
      macrocyclic peptide structures. In this review, we highlight recent advances in
      this emerging new area and discuss the opportunities created by these methods
      toward the discovery of new functional entities. 

PMID- 23856643
TI  - An electron rich porous extended framework as a heterogeneous catalyst for Diels
      Alder reactions.
AB  - An electron rich porous metal-organic framework (MOF) has been synthesized, which
      acts as an effective heterogeneous catalyst for Diels-Alder reactions through
      encapsulation of the reactants in confined nano-channels of the framework. 

PMID- 23856644
TI  - Generation of haploid embryonic stem cells from Macaca fascicularis monkey
      parthenotes.
AB  - Recent success in the derivation of haploid embryonic stem cells (haESCs) from
      mouse via parthenogenesis and androgenesis has enabled genetic screening in
      mammalian cells and generation of gene-modified animals. However, whether haESCs
      can be derived from primates remains unknown. Here, we report the derivation of
      haESCs from parthenogenetic blastocysts of Macaca fascicularis monkeys. These
      cells, termed as PG-haESCs, are pluripotent and can differentiate to cells of
      three embryonic germ layers in vitro or in vivo. Interestingly, the haploidy of
      one monkey PG-haESC line (MPH1) is more stable compared with that of the other
      one (MPH2), as shown by the existence of haploid cells for more than 140 days
      without fluorescence-activated cell sorting (FACS) enrichment of haploid cells.
      Importantly, transgenic monkey PG-haESC lines can be generated by lentivirus- and
      piggyBac transposon-mediated gene transfer. Moreover, genetic screening is
      feasible in monkey PG-haESCs. Our results demonstrate that PG-haESCs can be
      generated from monkeys, providing an ideal tool for genetic analyses in primates.

PMID- 23856645
TI  - Sirtuins as therapeutic targets of ALS.
AB  - Sirtuins have received a lot of attention in biological functions associated with
      metabolism, survival development, and most recently, neurodegeneration. The
      versatile role of sirtuins can be readily redirected for drug discovery studies
      for novel treatment in amyotrophic lateral sclerosis (ALS), as presented in this
      highlight, by sirtuin-mediated ketogenic responses influencing mitochondrial
      function. 

PMID- 23856646
TI  - To err is human: managing mistakes in manuscripts.

PMID- 23856647
TI  - On boundary stimulation and optimal boundary control of the bidomain equations.
AB  - The bidomain equations with Neumann boundary stimulation and optimal control of
      these stimuli are investigated. First an analytical framework for boundary
      control is provided. Then a parallel finite element based algorithm is devised
      and its efficiency is demonstrated not only for the direct problem but also for
      the optimal control problem. The computations realize a model configuration
      corresponding to optimal boundary defibrillation of a reentry phenomenon by
      applying current density stimuli. 

PMID- 23856648
TI  - Perfusion studies in senology.
AB  - Microcirculation imaging in breast cancer involves studying tissue enhancement
      after contrast injection, which is used to calculate perfusion and permeability.
      The magnitude of enhancement reflects blood and interstitial volumes. This
      technique has benefitted from advances in MRI, which allow large volumes to be
      acquired with a good compromise between temporal and spatial resolution. Software
      has also advanced enabling microcirculation maps to be calculated and
      heterogeneity to be analyzed. If permeability is increased and interstitial
      volume is reduced, the microcirculation imaging suggests a suspicious aggressive
      lesion and can be used for early assessment of neoadjuvant therapies by
      demonstrating restoration of normal functional indices, which precede
      morphological changes. 

PMID- 23856649
TI  - Treatment of onychomycosis using a submillisecond 1064-nm neodymium:yttrium
      aluminum-garnet laser.
AB  - BACKGROUND: Laser treatment has emerged as a novel treatment modality for
      onychomycosis. OBJECTIVE: We sought to determine thermal response and optical
      effects of a submillisecond neodymium:yttrium-aluminum-garnet (Nd:YAG) 1064-nm
      laser on common fungal nail pathogens, and the clinical efficacy and safety of
      the Nd:YAG 1064-nm laser on onychomycotic toenails. METHODS: A 4-part in vitro
      and in vivo study was conducted using a Nd:YAG 1064-nm laser. The first portion
      evaluated 3 different nail pathogens in suspension at 7 heat and time exposures.
      The second and third parts of the study irradiated pure fungal colonies. The
      final portion involved an in vivo treatment of toenails over 5 treatment
      sessions. RESULTS: A fungicidal effect for Trichophyton rubrum was seen at 50
      degrees C after 15 minutes, and for Epidermophyton floccosum at 50 degrees C
      after 10 minutes. Limited growth of Scytalidium was seen at 55 degrees C after 5
      minutes. No inhibition was observed after laser treatment of fungal colonies or
      suspensions. In vivo treatment of toenails showed no improvement in Onychomycosis
      Severity Index score. LIMITATIONS: The Nd:YAG 1064-nm laser was the only laser
      tested. CONCLUSIONS: Laser treatment of onychomycosis was not related to thermal
      damage or direct laser effects. In vivo treatment did not result in onychomycosis
      cure.

PMID- 23856650
TI  - Thromboxane A2 mediates iron-overload cardiomyopathy in mice through calcineurin
      nuclear factor of activated T cells signaling pathway.
AB  - BACKGROUND: Recent studies demonstrated that iron overload could enhance the
      production of arachidonic acid and prostanoid, suggesting a causal connection
      between these signals and iron-overload cardiomyopathy. However, information
      regarding the downstream signaling is limited. Because thromboxane A2 (TXA2) and
      prostacyclin are the 2 major prostanoids in the cardiovascular system, and TXA2
      plays a major role in vascular atherosclerosis and has pro-inflammatory
      characteristics, we intended to elucidate the role of TXA2 in iron-overload
      cardiomyopathy. METHODS AND RESULTS: A 4-week iron loading protocol was
      instituted for both TXAS gene-deleted (TXAS(-/-)) mice and wild-type (WT) mice,
      with less severe cardiac fibrosis and preserved normal left ventricular
      contraction in the TXAS(-/-) mice. Inflammatory profiles, including MCP-1, TNF
      alpha, IL-6, ICAM-1, and myeloperoxidase activity were also lower in the TXAS(-/
      ) as compared with WT littermates. TXAS supplement to the iron-injured TXAS(-/-)
      mice re-aggravated cardiac inflammation. Using a TXA2 analog, U46619, for NFAT
      reporter luciferase activity on cardiomyoctes, and intraperitonal injection of
      U46619 into nuclear factor of activated T cells (NFAT)-luciferase transgenic mice
      demonstrated that U46619 increase NFAT expression, and this expression, as well
      as TNF-alpha expression, can be blocked by TXA2 receptor antagonist (SQ29548),
      NFAT-SiRNA, calcineurin inhibitor, or calcium chelator. Finally, intraperitoneal
      injection of the TNF-alpha antibody, infliximab, into iron-injured mice decreased
      TXAS expression and attenuated cardiac fibrosis. CONCLUSIONS: TXA2 mediates iron
      overload cardiomyopathy through the TNF-alpha-associated calcineurin-NFAT
      signaling pathway. 

PMID- 23856651
TI  - Optical coherence tomography- 15 years in cardiology.
AB  - Since its invention in the late 1990s, intravascular optical coherence tomography
      (OCT) has been rapidly adopted in clinical research and, more recently, in
      clinical practice. Given its unprecedented resolution and high image contrast,
      OCT has been used to visualize plaque characteristics and to evaluate the
      vascular response to percutaneous coronary intervention. In particular, OCT is
      becoming the standard modality to evaluate in vivo plaque vulnerability,
      including the presence of lipid content, thin fibrous cap, or macrophage
      accumulation. Furthermore, OCT findings after stent implantation, such as strut
      apposition, neointimal hyperplasia, strut coverage, and neoatherosclerosis, are
      used as surrogate markers of the vascular response. New applications for OCT are
      being explored, such as transplant vasculopathy or non-coronary vascular imaging.
      Although OCT has contributed to cardiovascular research by providing a better
      understanding of the pathophysiology of coronary artery disease, data linking the
      images and clinical outcomes are lacking. Prospective data are needed to prove
      that the use of OCT improves patient outcomes, which is the ultimate goal of any
      clinical diagnostic tool.

PMID- 23856652
TI  - The substrate and ablation of ventricular tachycardia in patients with
      nonischemic cardiomyopathy.
AB  - The term "nonischemic cardiomyopathy" (NICM) designates a myocardial disease
      characterized by mechanical and/or electrical dysfunction in the absence of
      significant coronary artery disease, valvular heart disease, hypertension, or
      congenital heart disease. Although sustained ventricular tachycardia (VT) occurs
      in only 5% of patients with NICM, it is an important cause of sudden cardiac
      death. In this review we summarize the current understanding of the anatomic and
      electrophysiologic substrates of VT in the different types of NICM. In addition,
      we discuss recent progress and experience with catheter ablation of VT in these
      patients. 

PMID- 23856653
TI  - Medical therapy of chronic thromboembolic pulmonary hypertension.

PMID- 23856654
TI  - Vitamin C prevents intrauterine programming of in vivo cardiovascular dysfunction
      in the rat.
AB  - BACKGROUND: Fetal hypoxia is common and in vitro evidence supports its role in
      the programming of adult cardiovascular dysfunction through the generation of
      oxidative stress. Whether fetal chronic hypoxia programmes alterations in
      cardiovascular control in vivo, and if these alterations can be prevented by
      antioxidant treatment, is unknown. This study investigated the effects of
      prenatal fetal hypoxia, with and without maternal supplementation with vitamin C,
      on basal and stimulated cardiovascular function in vivo in the adult offspring at
      4 months of age in the rat. METHODS AND RESULTS: From days 6 to 20 of pregnancy,
      Wistar rats were subjected to Normoxia, Hypoxia (13% O2), Hypoxia+Vitamin C
      (5mg/ml in drinking water) or Normoxia+Vitamin C. At 4 months, male offspring
      were instrumented under urethane anaesthesia. Basal mean arterial blood pressure,
      heart rate and heart rate variability (HRV) were assessed, and stimulated
      baroreflex curves were generated with phenylephrine and sodium nitroprusside.
      Chronic fetal hypoxia increased the LF/HF HRV ratio and baroreflex gain, effects
      prevented by vitamin C administration during pregnancy. CONCLUSIONS: Chronic
      intrauterine hypoxia programmes cardiovascular dysfunction in vivo in adult rat
      offspring; effects ameliorated by maternal treatment with vitamin C. The data
      support a role for fetal chronic hypoxia programming cardiovascular dysfunction
      in the adult rat offspring in vivo through the generation of oxidative stress in
      utero. 

PMID- 23856655
TI  - Biomechanical constraints remain major risk factors for low back pain. Results
      from a prospective cohort study in French male employees.
AB  - BACKGROUND CONTEXT: Low back pain (LBP) is a major public health problem, with a
      considerable impact on workers. PURPOSE: To model the risk of LBP in the male
      general working population. STUDY DESIGN/SETTING: Repeated cross-sectional
      surveys in a wide occupational setting. PATIENT SAMPLE: A random sample of 2,161
      men working in various occupations in a French region participated in a first
      survey in 2002, and 1,313 of these (60.8%) participated in a second survey in
      2007. OUTCOME MEASURE: The self-reported prevalence of LBP during the previous
      week in the second survey. METHODS: Twenty-one biomechanical, organizational,
      psychosocial, and individual factors were assessed in the first survey. The
      association between these potential risk factors and the prevalence of later LBP
      (in the second survey) was studied, using multistep logistic regression models.
      RESULTS: Three hundred ninety-four men reported LBP in the second survey
      (prevalence 30.0%). The final multivariate model highlighted four risk factors:
      frequent bending (odds ratio [OR], 1.45, 95% confidence interval [CI], 1.07-1.97
      for bending forward only; and OR, 2.13, 95% CI, 1.52-3.00 for bending both
      forward and sideways), driving industrial vehicles (OR, 1.35; 95% CI, 1.00-1.81),
      working more hours than officially planned (OR, 1.38; 95% CI, 1.05-1.81), and
      reported low support from supervisors (OR, 1.35; 95% CI, 1.02-1.79). CONCLUSIONS:
      These results emphasize that biomechanical factors remain worth considering, even
      when psychosocial factors are taken into account, and provide a significant
      contribution to preventive strategies.

PMID- 23856656
TI  - Evaluation of hip flexion strength following lateral lumbar interbody fusion.
AB  - BACKGROUND CONTEXT: Lateral interbody fusion (LIF) is a minimally invasive
      procedure that is designed to achieve a solid interbody fusion while minimizing
      the damage to the surrounding soft tissue. Although short-term results have been
      promising, few data have been published to date regarding its risks and
      complication rate. PURPOSE: The aim was to evaluate the extent of injury to the
      psoas muscle after the LIF procedure by measuring hip flexion strength. STUDY
      DESIGN: A prospective case series was used in the study. METHOD: Hip flexion
      strength was measured using a handheld digital dynamometer while the patient was
      seated on a chair; the examiner held the device against the patient's attempt to
      flex the hip. Both sides were measured to compare the operated and nonoperated
      psoas muscles. Each side was measured three times and the average amount (in
      pounds) was recorded. Measurements were done before and after surgery on Day 2-3,
      at 2 weeks, 6 weeks, and at 3 and 6 months. RESULTS: Thirty-three patients were
      recruited for this study. Mean preoperative hip flexion strength values were
      20.7+/-3.47 lb and 21.3+/-4.31 lb for operated and nonoperated legs,
      respectively, with no significant difference (p=.85). With a mean of 11.2+/-2.24
      lb postoperative measurements on Day 2, the operated side showed statistically
      significant reduction of strength (p=.0001). The nonoperated side was also weaker
      postoperatively, but not significantly (mean=19.12+/-1.74 lb; p=.097). From the
      first follow-up visit at 2 weeks, the values on the operated leg had returned to
      baseline values (20.6, p=.97) and were not significantly different from
      preoperative values on either side. DISCUSSION: Hip flexion was weakened
      immediately after the LIF procedure, which may be attributed to psoas muscle
      injury during the procedure. However, this damage was temporary, with almost
      complete return to baseline values by 2 weeks.

PMID- 23856657
TI  - Sudden gains as a long-term predictor of treatment improvement among children in
      community mental health organizations.
AB  - OBJECTIVE: Sudden gains have been described as rapid, sizeable changes observed
      between treatment sessions and have been associated with improved treatment
      outcome in adults. The current study examined weekly sudden gains among children
      seeking treatment in the community mental health setting. METHOD: Participants
      were 161 children (age M = 10.58, SD = 1.73; 69.6% male; 47.8% Caucasian) and
      their parents who were randomized to one of three treatment modalities and were
      administered weekly and quarterly assessments throughout treatment. RESULTS: When
      idiographic (youth- and parent-identified "top problems") and nomothetic measures
      (standardized checklists) were used to calculate sudden gains (i.e., gain must be
      large: in absolute terms, relative to prior session, and relative to changes in
      prior and subsequent sessions), 20-42% of participants experienced at least one
      sudden gain during treatment. Most sudden gains occurred early in treatment, and
      session content of relaxation was associated with sudden gain presence. Using a
      modified Bonferonni correction, sudden gains predicted overall symptom levels at
      final assessment (i.e., last assessment obtained following post-treatment) even
      after controlling for pre-treatment symptom levels and magnitude of the overall
      gain from pre- to post-treatment. CONCLUSIONS: Suddenness of gains may have a
      direct effect on long-term treatment outcome among children in the community.

PMID- 23856658
TI  - Hexanuclear and undecanuclear iron(III) carboxylates as catalyst precursors for
      cyclohexane oxidation.
AB  - Two multinuclear complexes [Fe6(MU3-O)2(MU4
      O2)L10(OAc)2(H2O)2].2.625Et2O.2.375H2O (1) and [Fe(III)11Cl(MU4-O)3(MU3
      O)5L16(dmf)(2.5)(H2O)(0.5)].Et2O.1.25dmf.3.8H2O (2), where HL = 3,4,5
      trimethoxybenzoic acid and dmf = dimethylformamide, have been prepared from
      trinuclear iron(III) carboxylates via their structural rearrangement in
      dimethylformamide or diethyl ether-dimethylformamide 9:1, respectively, and slow
      vapor diffusion of diethyl ether into the reaction mixture. Both compounds have
      been characterized by X-ray diffraction, optical, Mossbauer spectroscopy, and
      magnetic measurements. Complex 1 possesses a hexanuclear ferric peroxido-dioxido
      {Fe6(O2)(O)2}(12+) core unit, which adopts a recliner conformation, while complex
      2 contains an unprecedented {Fe11O8Cl}(16+) core, in which 9 ferric ions are six
      coordinate and the remaining two are five-coordinate. Another structural feature
      of note of the undecanuclear core is the presence of a deformed cubane entity
      {Fe4(MU3-O)(MU4-O)3}(4+). Both complexes act as catalyst precursors for the
      oxidation of cyclohexane to cyclohexanol and cyclohexanone with aqueous H2O2, in
      the presence of pyrazinecarboxylic acid. Remarkable TONs and TOFs (the latter
      mainly for 1) with concomitant quite good yields have been achieved under mild
      conditions. Moreover, 1 exhibits remarkably high activity in an exceptionally
      short reaction time (45 min), being unprecedented for any metal catalyzed alkane
      oxidation by H2O2. The catalytic reactions proceed via Fenton type chemistry.

PMID- 23856659
TI  - Nitrous oxide: deep in the zone of uncertainty.

PMID- 23856661
TI  - How Pan's rejection led to the syringe's injection.

PMID- 23856660
TI  - Influence of nitrous oxide anesthesia, B-vitamins, and MTHFR gene polymorphisms
      on perioperative cardiac events: the vitamins in nitrous oxide (VINO) randomized
      trial.
AB  - BACKGROUND: Nitrous oxide causes an acute increase in plasma homocysteine that is
      more pronounced in patients with the methylenetetrahydrofolate reductase (MTHFR)
      C677T or A1298C gene variant. In this randomized controlled trial, the authors
      sought to determine whether patients carrying the MTHFR C677T or A1298C variant
      had a higher risk for perioperative cardiac events after nitrous oxide anesthesia
      and whether this risk could be mitigated by B-vitamins. METHODS: The authors
      randomized adult patients with cardiac risk factors undergoing noncardiac
      surgery, to receive nitrous oxide plus intravenous B-vitamins before and after
      surgery, or to nitrous oxide and placebo. Serial cardiac biomarkers and 12-lead
      electrocardiograms were obtained. The primary study endpoint was the incidence of
      myocardial injury, as defined by cardiac troponin I increase within the first 72
      h after surgery. RESULTS: A total of 500 patients completed the trial. Patients
      who were homozygous for either MTHFR C677T, or A1298C gene variant (n=98; 19.6%)
      had no increased rate of postoperative cardiac troponin I increase compared with
      wild-type and heterozygous patients (11.2 vs. 14.0%; relative risk 0.96; 95% CI,
      0.85-1.07; P=0.48). B-vitamins blunted the rise in homocysteine, but had no
      effect on cardiac troponin I increase compared with patients receiving placebo
      (13.2 vs. 13.6%; relative risk 1.02; 95% CI 0.78 to 1.32; P=0.91). CONCLUSIONS:
      Neither MTHFR C677T and A1298C gene variant, nor acute homocysteine increase are
      associated with perioperative cardiac troponin increase after nitrous oxide
      anesthesia. B-vitamins blunt nitrous oxide-induced homocysteine increase but have
      no effect on cardiac troponin I increase.

PMID- 23856662
TI  - From chloroform to extract of meat: chemist and entrepreneur Liebig.

PMID- 23856663
TI  - De Jarnette's Optic Chromatic System of Anesthesia.

PMID- 23856664
TI  - Anesthetic exposure and academic achievement: missing the forest for the trees.

PMID- 23856665
TI  - In reply.

PMID- 23856666
TI  - Radial artery catherization.

PMID- 23856667
TI  - In reply.

PMID- 23856668
TI  - Clinical relevance of urodynamic parameter changes in thoracic epidural
      analgesia.

PMID- 23856669
TI  - In reply.

PMID- 23856674
TI  - Obstetric interventions for women with type 1 or type 2 diabetes.
AB  - OBJECTIVE: To determine whether differences exist in the rates of obstetric
      intervention between women with type 1 diabetes and those with type 2 diabetes,
      and whether there has been any change in cesarean rates over time, paralleling
      that seen in the general obstetric population. METHODS: Data were examined from a
      prospectively collected series on the outcomes of 1030 deliveries (382 by women
      with type 1 diabetes, 648 by women with type 2 diabetes) from 1988 to 2008.
      RESULTS: There was a secular trend to increasing maternal age (type 1, P < 0.003;
      type 2, P < 0.03). Intervention rates (induction of labor or elective cesarean)
      did not differ between type 1 (88%) and type 2 (85%) diabetes. The overall
      cesarean rate was 52%-55% with no secular trend. Poorer glycemic control in early
      pregnancy and primiparity were associated with primary cesarean in both groups.
      In women with type 1 diabetes, greater maternal obesity and retinopathy were also
      associated with primary cesarean. CONCLUSION: Intervention rates are high in
      pregnancies among women with type 1 diabetes and those with type 2 diabetes but
      they have not changed significantly. Secular trends toward increasing maternal
      age and obesity suggest that intervention rates are unlikely to decrease in the
      near future.

PMID- 23856675
TI  - Association between delivery of a small-for-gestational-age neonate and long-term
      maternal cardiovascular morbidity.
AB  - OBJECTIVE: To investigate whether delivering a small-for-gestational-age (SGA)
      newborn is a risk factor for subsequent long-term maternal cardiovascular
      morbidity. METHODS: Data were analyzed from consecutive pregnant women who
      delivered at Soroka University Medical Center, Beer-Sheva, Israel, between 1988
      and 1999, and were followed-up retrospectively until 2010. Long-term
      cardiovascular morbidity was compared among women with and without SGA neonates.
      RESULTS: During the study period, 47 612 deliveries met the inclusion criteria,
      and 4411 (9.3%) women delivered an SGA neonate. Delivery of an SGA neonate was a
      risk factor for long-term complex cardiovascular events, including congestive
      heart failure, hypertensive heart and kidney disease, and acute cor pulmonale
      (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.3-4.4; P = 0.006); and
      long-term cardiovascular mortality (OR, 3.4; 95% CI, 1.5-7.6; P = 0.006). Women
      who delivered an SGA neonate had a significantly higher risk for cardiovascular
      mortality during the follow-up period (Kaplan-Meier survival analysis, P =
      0.002). Delivery of an SGA neonate remained an independent risk factor for long
      term maternal cardiovascular mortality (Cox multivariable regression: adjusted
      hazard ratio, 3.5; 95% CI, 1.5-8.2; P = 0.004). CONCLUSION: Delivery of an SGA
      neonate is an independent risk factor for long-term cardiovascular morbidity in a
      follow-up period of more than 10 years.

PMID- 23856676
TI  - A review of global access to emergency contraception.
AB  - BACKGROUND: Emergency contraception has been known for several decades, and
      dedicated products have been on the market for close to 20 years. Yet it is
      unclear whether women, particularly in low-resource countries, have access to
      this important second-chance method of contraception. OBJECTIVES: To review
      relevant policies, regulations, and other factors related to access to emergency
      contraception worldwide. SEARCH STRATEGY: A wide range of gray literature was
      reviewed, several specific studies were commissioned, and a number of online
      databases were searched. MAIN RESULTS: Several positive policies and regulations
      are in place: emergency contraception products are registered in the majority of
      countries around the world, listed in many countries' essential medicines lists,
      included in widely used guidance, and supported by most donors. Yet analysis of
      demographic data shows that the majority of women in low-income countries have
      never heard of emergency contraception, and surveys find that many providers have
      negative attitudes toward providing emergency contraception. CONCLUSIONS: Despite
      more than a decade of concerted international and country-level efforts to ensure
      that women have access to emergency contraception, accessibility remains limited.

PMID- 23856677
TI  - Infection: Myocardial disease in patients with HIV.

PMID- 23856678
TI  - Anticoagulation therapy: Apixaban indications set to AMPLIFY?

PMID- 23856680
TI  - Do scientists trace hot topics?
AB  - Do scientists follow hot topics in their scientific investigations? In this
      paper, by performing analysis to papers published in the American Physical
      Society (APS) Physical Review journals, it is found that papers are more likely
      to be attracted by hot fields, where the hotness of a field is measured by the
      number of papers belonging to the field. This indicates that scientists generally
      do follow hot topics. However, there are qualitative differences among scientists
      from various countries, among research works regarding different number of
      authors, different number of affiliations and different number of references.
      These observations could be valuable for policy makers when deciding research
      funding and also for individual researchers when searching for scientific
      projects. 

PMID- 23856679
TI  - Vascular endothelial growth factor in heart failure.
AB  - Heart failure is a devastating condition, the progression of which culminates in
      a mismatch of oxygen supply and demand, with limited options for treatment. Heart
      failure has several underlying causes including, but not limited to, ischaemic
      heart disease, valvular dysfunction, and hypertensive heart disease.
      Dysfunctional blood vessel formation is a major problem in advanced heart
      failure, regardless of the aetiology. Vascular endothelial growth factor (VEGF)
      is the cornerstone cytokine involved in the formation of new vessels. A multitude
      of investigations, at both the preclinical and clinical levels, have garnered
      valuable information on the potential utility of targeting VEGF as a treatment
      option for heart failure. However, clinical trials of VEGF gene therapy in
      patients with coronary artery disease or peripheral artery disease have not, to
      date, demonstrated clinical benefit. In this Review, we outline the biological
      characterization of VEGF, and examine the evidence for its potential therapeutic
      application, including the novel concept of VEGF as adjuvant therapy to stem cell
      transplantation, in patients with heart failure. 

PMID- 23856681
TI  - Alternate-day, low-dose aspirin and cancer risk: long-term observational follow
      up of a randomized trial.
AB  - BACKGROUND: Recent evidence suggests that daily aspirin use decreases cancer
      risk, particularly for colorectal cancer, but evidence for alternate-day use is
      scant. OBJECTIVE: To examine the association between long-term, alternate-day,
      low-dose aspirin and cancer in healthy women. DESIGN: Observational follow-up of
      a randomized trial. SETTING: Female health professionals. PARTICIPANTS: 39,876
      women aged 45 years or older in the Women's Health Study (ClinicalTrials.gov:
      NCT00000479), 33 682 of whom continued observational follow-up. INTERVENTION: 100
      mg of alternate-day aspirin or placebo through March 2004, with a median 10-year
      follow-up. Posttrial follow-up continued through March 2012. MEASUREMENTS: Cancer
      incidence. RESULTS: A total of 5071 cancer cases (including 2070 breast, 451
      colorectal, and 431 lung cancer cases) and 1391 cancer deaths were confirmed.
      Over the entire follow-up, aspirin had no association with total (hazard ratio
      [HR], 0.97 [95% CI, 0.92 to 1.03]; P = 0.31), breast (HR, 0.98 [CI, 0.90 to
      1.07]; P = 0.65), or lung (HR, 1.04 [CI, 0.86 to 1.26]; P = 0.67) cancer.
      Colorectal cancer was reduced in the aspirin group (HR, 0.80 [CI, 0.67 to 0.97];
      P = 0.021), primarily for proximal colon cancer (HR, 0.73 [CI, 0.55 to 0.95]; P =
      0.022). The difference emerged after 10 years, with a posttrial reduction of 42%
      (HR, 0.58 [CI, 0.42 to 0.80]; P < 0.001). There was no extended effect on cancer
      deaths or colorectal polyps. More gastrointestinal bleeding (HR, 1.14 [CI, 1.06
      to 1.22]; P < 0.001) and peptic ulcers (HR, 1.17 [CI, 1.09 to 1.27]; P < 0.001)
      occurred in the aspirin group. LIMITATIONS: Not all women received extended
      follow-up, and posttrial ascertainment bias cannot be ruled out. Gastrointestinal
      bleeding, peptic ulcers, and polyps were self-reported during extended follow-up.
      CONCLUSION: Long-term use of alternate-day, low-dose aspirin may reduce risk for
      colorectal cancer in healthy women.

PMID- 23856682
TI  - Effect of electronic health records on health care costs: longitudinal
      comparative evidence from community practices.
AB  - BACKGROUND: The United States is aiming to achieve nationwide adoption of
      electronic health records (EHRs) but lacks robust empirical evidence to
      anticipate the effect on health care costs. OBJECTIVE: To assess short-term cost
      savings from community-wide adoption of ambulatory EHRs. DESIGN: Longitudinal
      trial with parallel control group. SETTING: Natural experiment in which 806
      ambulatory clinicians across 3 Massachusetts communities adopted subsidized EHRs.
      Six matched control communities applied but were not selected to participate.
      PATIENTS: 47,979 intervention patients and 130,603 control patients.
      MEASUREMENTS: Monthly standardized health care costs from commercial claims data
      from January 2005 to June 2009, including total cost, inpatient cost, and
      ambulatory cost and its subtypes (pharmacy, laboratory, and radiology). Projected
      savings per member per month (PMPM), excluding EHR adoption costs. RESULTS:
      Ambulatory EHR adoption did not impact total cost (pre- to postimplementation
      difference in monthly trend change, -0.30 percentage point; P = 0.135), but the
      results favored savings (95% CI, $21.95 PMPM in savings to $1.53 PMPM in higher
      costs). It slowed ambulatory cost growth (difference in monthly trend change, 
      0.35 percentage point; P = 0.012); projected ambulatory savings were $4.69 PMPM
      (CI, $8.45 to $1.09 PMPM) (3.10% of total PMPM cost). Ambulatory radiology costs
      decreased (difference in monthly trend change, -1.61 percentage points; P <
      0.001), with projected savings of $1.61 PMPM (1.07% of total PMPM cost).
      LIMITATIONS: Intervention communities were not randomly selected and received
      implementation support, suggesting that results may represent a best-case
      scenario. Confounding is possible. CONCLUSION: Using commercially available EHRs
      in community practices seems to modestly slow ambulatory cost growth. Broader
      changes in the organization and payment of care may prompt clinicians to use EHRs
      in ways that result in more substantial savings.

PMID- 23856683
TI  - Conceptual and technical challenges in network meta-analysis.
AB  - The increase in treatment options creates an urgent need for comparative
      effectiveness research. Randomized, controlled trials comparing several
      treatments are usually not feasible, so other methodological approaches are
      needed. Meta-analyses provide summary estimates of treatment effects by combining
      data from many studies. However, an important drawback is that standard meta
      analyses can compare only 2 interventions at a time. A new meta-analytic
      technique, called network meta-analysis (or multiple treatments meta-analysis or
      mixed-treatment comparison), allows assessment of the relative effectiveness of
      several interventions, synthesizing evidence across a network of randomized
      trials. Despite the growing prevalence and influence of network meta-analysis in
      many fields of medicine, several issues need to be addressed when constructing
      one to avoid conclusions that are inaccurate, invalid, or not clearly justified.
      This article explores the scope and limitations of network meta-analysis and
      offers advice on dealing with heterogeneity, inconsistency, and potential sources
      of bias in the available evidence to increase awareness among physicians about
      some of the challenges in interpretation. 

PMID- 23856684
TI  - Alternate-day, low-dose aspirin and cancer risk.

PMID- 23856685
TI  - Reducing the costs of U.S. health care: the role of electronic health records.

PMID- 23856686
TI  - On not being her doctor.

PMID- 23856687
TI  - Computed tomography screening for lung cancer.

PMID- 23856688
TI  - Computed tomography screening for lung cancer.

PMID- 23856689
TI  - Computed tomography screening for lung cancer.

PMID- 23856690
TI  - Online medical professionalism.

PMID- 23856691
TI  - Online medical professionalism.

PMID- 23856692
TI  - Online medical professionalism.

PMID- 23856693
TI  - Deaths associated with avian influenza A(H7N9) virus in China.

PMID- 23856695
TI  - Summaries for patients. The effect of low-dose aspirin on colorectal cancer risk
      in women.

PMID- 23856696
TI  - ACP Journal Club. Review: Ultrasonography reduces failed lumbar punctures and
      epidural catheterizations.

PMID- 23856697
TI  - ACP Journal Club. Screening for abdominal aortic aneurysm (AAA) in older men
      reduced AAA mortality at 13 years.

PMID- 23856698
TI  - ACP Journal Club. Review: Thiazide, citrate, or allopurinol reduces recurrence
      after >= 2 kidney stone episodes.

PMID- 23856699
TI  - ACP Journal Club. Surgery and physical therapy did not differ for function in
      meniscal tears with knee osteoarthritis.

PMID- 23856700
TI  - ACP Journal Club. Review: Statins reduce mortality and major vascular events in
      patients with no history of CV disease.

PMID- 23856701
TI  - ACP Journal Club. Meta-analysis: Atorvastatin reduces CV events and increases new
      onset diabetes in patients with coronary disease.

PMID- 23856702
TI  - ACP Journal Club. PCI was not as effective as CABG for severe coronary artery
      disease at 5 years.

PMID- 23856703
TI  - ACP Journal Club. SYNTAX score II predicted mortality after PCI or CABG in
      complex CAD better than SYNTAX score.

PMID- 23856704
TI  - ACP Journal Club. Nonemergency PCI without onsite cardiac surgery was noninferior
      to PCI with onsite services for MACE.

PMID- 23856705
TI  - ACP Journal Club. Review: New oral anticoagulants added to antiplatelets reduce
      CV events but increase bleeding after ACS.

PMID- 23856706
TI  - ACP Journal Club. Apixaban reduced stroke or systemic embolism in AF more than
      warfarin regardless of type or duration of AF.

PMID- 23856707
TI  - ACP Journal Club. Review: Routine venous thromboembolism prophylaxis in
      hospitalized frail older patients has uncertain benefit.

PMID- 23856708
TI  - Deferred imitation and declarative memory in domestic dogs.
AB  - This study demonstrates for the first time deferred imitation of novel actions in
      dogs (Canis familiaris) with retention intervals of 1.5 min and memory of
      familiar actions with intervals ranging from 0.40 to 10 min. Eight dogs were
      trained using the 'Do as I do' method to match their own behaviour to actions
      displayed by a human demonstrator. They were then trained to wait for a short
      interval to elapse before they were allowed to show the previously demonstrated
      action. The dogs were then tested for memory of the demonstrated behaviour in
      various conditions, also with the so-called two-action procedure and in a control
      condition without demonstration. Dogs were typically able to reproduce familiar
      actions after intervals as long as 10 min, even if distracted by different
      activities during the retention interval and were able to match their behaviour
      to the demonstration of a novel action after a delay of 1 min. In the two-action
      procedure, dogs were typically able to imitate the novel demonstrated behaviour
      after retention intervals of 1.5 min. The ability to encode and recall an action
      after a delay implies that facilitative processes cannot exhaustively explain the
      observed behavioural similarity and that dogs' imitative abilities are rather
      based on an enduring mental representation of the demonstration. Furthermore, the
      ability to imitate a novel action after a delay without previous practice
      suggests presence of declarative memory in dogs. 

PMID- 23856710
TI  - Left hemisphere lateralization for lexical and acoustic pitch processing in
      Cantonese speakers as revealed by mismatch negativity.
AB  - For nontonal language speakers, speech processing is lateralized to the left
      hemisphere and musical processing is lateralized to the right hemisphere (i.e.,
      function-dependent brain asymmetry). On the other hand, acoustic temporal
      processing is lateralized to the left hemisphere and spectral/pitch processing is
      lateralized to the right hemisphere (i.e., acoustic-dependent brain asymmetry).
      In this study, we examine whether the hemispheric lateralization of lexical pitch
      and acoustic pitch processing in tonal language speakers is consistent with the
      patterns of function- and acoustic-dependent brain asymmetry in nontonal language
      speakers. Pitch contrast in both speech stimuli (syllable /ji/ in Experiment 1)
      and nonspeech stimuli (harmonic tone in Experiment 1; pure tone in Experiment 2)
      was presented to native Cantonese speakers in passive oddball paradigms. We found
      that the mismatch negativity (MMN) elicited by lexical pitch contrast was
      lateralized to the left hemisphere, which is consistent with the pattern of
      function-dependent brain asymmetry (i.e., left hemisphere lateralization for
      speech processing) in nontonal language speakers. However, the MMN elicited by
      acoustic pitch contrast was also left hemisphere lateralized (harmonic tone in
      Experiment 1) or showed a tendency for left hemisphere lateralization (pure tone
      in Experiment 2), which is inconsistent with the pattern of acoustic-dependent
      brain asymmetry (i.e., right hemisphere lateralization for acoustic pitch
      processing) in nontonal language speakers. The consistent pattern of function
      dependent brain asymmetry and the inconsistent pattern of acoustic-dependent
      brain asymmetry between tonal and nontonal language speakers can be explained by
      the hypothesis that the acoustic-dependent brain asymmetry is the consequence of
      a carryover effect from function-dependent brain asymmetry. Potential
      evolutionary implication of this hypothesis is discussed. 

PMID- 23856709
TI  - Contribution of electromechanical coupling between Kv and Ca v1.2 channels to
      coronary dysfunction in obesity.
AB  - Previous investigations indicate that diminished functional expression of voltage
      dependent K(+) (KV) channels impairs control of coronary blood flow in
      obesity/metabolic syndrome. The goal of this investigation was to test the
      hypothesis that KV channels are electromechanically coupled to CaV1.2 channels
      and that coronary microvascular dysfunction in obesity is related to subsequent
      increases in CaV1.2 channel activity. Initial studies revealed that inhibition of
      KV channels with 4-aminopyridine (4AP, 0.3 mM) increased intracellular [Ca(2+)],
      contracted isolated coronary arterioles and decreased coronary reactive
      hyperemia. These effects were reversed by blockade of CaV1.2 channels. Further
      studies in chronically instrumented Ossabaw swine showed that inhibition of
      CaV1.2 channels with nifedipine (10 MUg/kg, iv) had no effect on coronary blood
      flow at rest or during exercise in lean swine. However, inhibition of CaV1.2
      channels significantly increased coronary blood flow, conductance, and the
      balance between coronary flow and metabolism in obese swine (P < 0.05). These
      changes were associated with a ~50 % increase in inward CaV1.2 current and
      elevations in expression of the pore-forming subunit (alpha1c) of CaV1.2 channels
      in coronary smooth muscle cells from obese swine. Taken together, these findings
      indicate that electromechanical coupling between KV and CaV1.2 channels is
      involved in the regulation of coronary vasomotor tone and that increases in
      CaV1.2 channel activity contribute to coronary microvascular dysfunction in the
      setting of obesity. 

PMID- 23856711
TI  - Left ventricular activation imaging by 3-dimensional speckle-tracking
      echocardiography. Comparison with electrical activation mapping.
AB  - BACKGROUND: Activation imaging with 3-dimensional speckle-tracking
      echocardiography (3D-STE) aims to visualize the time required for the onset of
      regional contraction from QRS onset. We hypothesized that the optimal setting of
      activation imaging was associated with electrical activation. This study was
      designed to determine an optimal setting of activation imaging with 3D-STE in
      comparison with that of a voltage mapping system and to assess the feasibility of
      this imaging method. METHODS AND RESULTS: We enrolled 7 patients who underwent
      electrical voltage mapping. Regional deformation was measured by area change
      ratio (ACR) with 3D-STE. Activation imaging data were obtained at 10%, 25%, 50%,
      and 100% of maximal ACR values as the threshold for onset of regional
      contraction. Duration of LV electrical intraventricular activation time
      (IVAT(electrical)) by voltage mapping and mechanical IVAT (IVAT(mechanical)) by
      activation imaging was defined as the time difference between the first and
      latest endocardial activation sites. We obtained 21 data sets under various
      conduction patterns and pacing configurations. The strongest correlation between
      IVAT(mechanical) and IVAT(electrical) was observed at 25% of maximal ACR values
      (IVAT(electrical)=0.47 * IVAT(mechanical)+20, R=0.80, P<0.001). Concordance of
      the first and latest activated segments between activation imaging and voltage
      mapping was 90.5% at this setting (19 studies). CONCLUSIONS: Activation imaging
      with 3D-STE may be a feasible noninvasive method of dyssynchrony imaging based on
      electromechanical coupling. 

PMID- 23856712
TI  - Diuretics in normotensive patients with acute pulmonary embolism and right
      ventricular dilatation.
AB  - BACKGROUND: The benefit of load expansion is controversial in acute pulmonary
      embolism (PE). The aim of this study was to evaluate the benefit of furosemide in
      cases of normotensive acute PE. METHODS AND RESULTS: We retrospectively included
      70 consecutive normotensive patients (systolic blood pressure >= 90 mmHg)
      admitted for acute PE with right ventricular dilation. Overall, 40 patients were
      treated during the first 24h by repeated bolus of furosemide (78 +/- 42 mg, range
      40-160 mg) and 30 patients received isotonic saline solution (1.6 +/- 0.9L).
      Severity of hemodynamic status was similar in both groups, but patients in the
      furosemide group were older and had a greater creatinine level. At 24h, only the
      furosemide group had a decreased shock index (0.82 +/- 0.22 vs. 0.63 +/- 0.16,
      P<0.0001) with improved systolic blood pressure (118 +/- 18 vs. 133 +/- 17 mmHg,
      P<0.0001), and creatinine levels. After treatment, there were fewer patients with
      simplified pulmonary embolism severity index >= 1 in the diuretic group (45% vs.
      55%, P=0.03) than in the fluid expansion group (47% vs. 40%, P<0.0001). Finally,
      oxygen requirement at 24h decreased only in the diuretic group (75% to 47%,
      P=0.0004), and in-hospital survival without death and PE-related shock were
      similar between the 2 groups. CONCLUSIONS: In normotensive PE with RV dilatation,
      diuretics may improve hemodynamics and oxygenation requirement. 

PMID- 23856713
TI  - Vaccination of healthy children against seasonal influenza: a European
      perspective.
AB  - Despite ample evidence for the great burden that annual influenza epidemics place
      on children and society in general, few European countries currently recommend
      influenza vaccination of healthy children of any age. The most frequently cited
      reasons for reluctance to extend general vaccine recommendations to children
      include the view that influenza is a mild illness of limited clinical importance,
      lack of country-specific data on disease burden, uncertainty about the efficacy
      and safety of influenza vaccines in children and inadequate evidence of cost
      effectiveness of vaccinating children. In recent years, several clinical studies
      have provided new and important information that help address many of these areas
      of question and concern. In light of this newly available scientific evidence,
      influenza vaccine recommendations for children should be properly reevaluated in
      all European countries. Furthermore, to allow for variation in costs and patterns
      of healthcare delivery between different countries, cost-effectiveness analyses
      of influenza vaccination of healthy children should be performed in each country
      or region. Finally, increased efforts should be made to educate both healthcare
      professionals and the great public about recent findings and advances in the
      field of pediatric influenza. 

PMID- 23856714
TI  - Central line-associated bloodstream infection in children: an update on
      treatment.

PMID- 23856715
TI  - Management of pediatric contacts of multidrug resistant tuberculosis in the
      United Kingdom.

PMID- 23856716
TI  - "Matching Michigan" in neonatal intensive care units: a plea for uniform data
      presentation.

PMID- 23856717
TI  - Insulin-dependent diabetes mellitus is associated with infections through
      reduction of antibody response to T-cell-dependent antigens.

PMID- 23856718
TI  - Author reply: To PMID 23188099.

PMID- 23856720
TI  - Nuclear microbiology--bacterial assault on the nucleolus.

PMID- 23856721
TI  - The secret garden's gardeners. Research increasingly appreciates the crucial role
      of gut viruses for human health and disease.

PMID- 23856722
TI  - Lost in translation. Scientists need to adapt to a postmodern world;
      constructivism can offer a way.

PMID- 23856723
TI  - Society and GMOs--chicken and egg? The lessons from the GM crops debate in Europe
      over risk management and communication provide valuable pointers for the upcoming
      debate on GM animals.

PMID- 23856724
TI  - Phoretic mites identified on Andean hummingbirds (Trochilidae) of Caldas,
      Colombia.
AB  - Within the bird-plant-mite system, the relationship between hummingbirds,
      flowers, and mites remains poorly understood. In this study, we evaluated the
      degree of association between nasal mites and eight species of Andean
      hummingbirds in Colombia (Amazilia saucerrottei, A. tzacatl, Chalybura buffonii,
      Chlorostilbon mellisugus, Florisuga mellivora, Glaucis hirsutus, Phaethornis guy
      and P. striigularis). Over a five-month period (trapping effort 360 hours/month),
      a total of 178 birds were captured, from which 81 mite specimens were collected
      and identified as belonging to three genera (Proctolaelaps, Rhinoseius and
      Tropicoseius) spanning eleven species. This is the first report of its kind from
      Colombia on the identification of the mite species P. rabulatus, R. luteyni, R.
      rafinskii, T. berryi, T. colwelli, T. erro and T. uniformis and the first record
      of P. guy as phoretic host for Proctolaelaps rabulatus. Morphological
      characteristics (length of the dorsal plate, width of the dorsal plate and setae
      z5 length) alone failed to distinguish between mite species. The ecologic impact
      of this relationship on flowers with respect to nectar and pollen availability
      and the effect of mites on pollination by hummingbirds needs to be determined. 

PMID- 23856725
TI  - Occurrence of Shiga-toxigenic Escherichia coli in Stomoxys calcitrans (Diptera:
      Muscidae).
AB  - This study aimed to verify the occurrence of Shiga toxin-producing Escherichia
      coli (STEC) strains in three distinct anatomic parts of the stable fly Stomoxys
      calcitrans by multiplex polymerase chain reaction (PCR Multiplex). According to
      the results obtained, E. coli was identified in 19.5% of the stable flies. Shiga
      toxin genes were detected in 13% of the E. coli isolated, most frequently from
      the surface, followed by abdominal digestive tract and mouth apparatus of
      insects, respectively. This is the first study to detect presence of STEC in
      Stomoxys calcitrans in Brazil; it has also revealed the potential role of stable
      flies as carriers of pathogenic bacterial agents. 

PMID- 23856726
TI  - New record, host and localities of bat mite of genus Chirnyssoides (Acari,
      Sarcoptiformes, Sarcoptidae).
AB  - Chirnyssoides parasitizes the anterior and posterior edges of bat wing membranes.
      Possibly due to a lack of studies, its distribution is believed to be restricted
      to a few countries of Central and South America, but its actual range is probably
      wider. The purpose of this paper is to report the presence of Chirnyssoides
      amazonae on the bat Carollia perspicillata in the state of Rio de Janeiro,
      Brazil, and to present a checklist of hosts and localities for Chirnyssoides.
      Eleven females and 22 egg clusters of C. amazonae were collected from 11
      individuals of C. perspicillata captured in Tingua Biological Reserve using mist
      nets. Our search of the literature came up with 69 records of Chirnyssoides.
      There are reports of Chirnyssoides caparti, Chirnyssoides amazonae, Chirnyssoides
      brasiliensis and Chirnyssoides phyllostomus in Brazil. This paper reports the
      first record of Chirnyssoides amazonae in the state of Rio de Janeiro and the
      second in Brazil, indicating that their known distribution extends to the south.
      There are records of C. amazonae and C. surinamensis parasitizing C.
      perspicillata, but this is the first record of C. amazonae on C. perspicillata in
      Brazil. 

PMID- 23856727
TI  - Cytauxzoon felis and 'Candidatus Mycoplasma haemominutum' coinfection in a
      Brazilian domestic cat (Felis catus).
AB  - This article describes the first detection of Cytauxzoon felis, using molecular
      techniques, in a naturally infected domestic cat from Brazil, South America.
      Coinfection with 'Candidatus Mycoplasma haemominutum' was also found. The
      molecular identification of the piroplasmid species was performed by Polymerase
      Chain Reaction (PCR) and sequencing analysis. A 284 pb fragment of the gene
      encoding the 18S ribosomal RNA region was amplified and showed 99% identity with
      other C. felis strains from North America. In addition, PCR-RFLP (restriction
      fragment length polymorphism) analysis, which amplifies a 595 bp fragment of the
      gene encoding 16S ribosomal RNA of some bacterial species, identified the co
      infecting species as 'Candidatus M. haemominutum'. 

PMID- 23856728
TI  - Prevalence and zoonotic aspects of small ruminant mange in the lateritic and
      waterlogged zones, southern Benin.
AB  - An epidemiological survey was undertaken from March to September 2010 to assess
      the prevalence and zoonotic aspects of scabies in small ruminants in two agro
      ecological zones in southern Benin. Small ruminant (n = 444) smallholders and
      1,807 of their animals (1,233 West African dwarf goats and 574 West African dwarf
      sheep) were included in the study. The animals underwent physical examination
      and, when scabies-like lesions were found, crusts and integument scrapings were
      collected for microscopic parasitological tests. The samples collected in each
      survey were coded in accordance with the owner-animal pairings in order to assess
      the degree of correlation between mange cases in humans (smallholders) and their
      animals. The overall prevalence of scabies was 28.33% and 9.5% in animals and
      smallholders (human cases) respectively. Infestations were significantly (p <
      0.001) more frequent in goats (39.6%) than in sheep. The uniqueness of the
      etiological agent (Sarcoptes scabiei), the very high predictive value of human
      scabies in infected farms (83.67%) and a very high odds ratio (OR = 2,019.25)
      indicate that small ruminant scabies has been transmitted to smallholders by
      their animals. Close contact between these smallholders and their animals was a
      determining factor in this interspecies communicability of sarcoptic mange. 

PMID- 23856729
TI  - Prevalence and risk factors associated with anti-Toxoplasma gondii antibodies in
      sheep from Bahia state, Brazil.
AB  - In this study, we aimed to determine the prevalence of Toxoplasma gondii
      antibodies and identify risk factors associated with this infection in sheep from
      the southern region of Bahia state. Between February and December 2010, 795 sheep
      from 31 farms located in nine municipalities were tested. We found seroprevalence
      of 30.2% (240/795), with titers of 64 (38.3%), 256 (34.2%), 1,024 (18.3%), and
      4,096 (9.2%) by Indirect Fluorescent Antibody Test (IFAT). Seropositive sheep
      were detected in all farms sampled. Univariate statistical analysis detected
      association between T. gondii seropositivity and the variables age, use of fresh
      food mainly, water source, stocking rate, production system, presence and number
      of cats on the farm, and transit of cats (p < 0.05). In the logistic regression
      model, transit of cats (p = 0.001), production system (p = 0.007), and age (p =
      0.027) were identified as risk factors associated with T. gondii infection. 

PMID- 23856730
TI  - Calodium hepaticum (Nematoda: Capillariidae) in synanthropic rodents (Rattus
      norvegicus and Rattus rattus) in Eastern Amazonia.
AB  - Calodium hepaticum (syn. Capillaria hepatica) is a trichurid nematode that
      parasitizes the hepatic parenchyma of rodents and other mammals. Infections in
      humans are rare, although they have been reported worldwide. A number of factors
      contribute to the distribution of this zoonosis, particularly the presence of
      dense populations of rodents associated with relatively poor urban environments,
      such as those found in parts of the northern Brazilian city of Belem in the
      eastern Amazon Basin. This study quantified Calodium infections in commensal
      synanthropic rodents in Belem. Rodents were captured in three neighborhoods
      characterized by poor public sanitation and the city's highest incidence of human
      leptospirosis. A total of 50 rodents were captured (26 Rattus rattus and 24 R.
      norvegicus), and 23 (10 R. rattus and 13 R. norvegicus) presented macroscopic
      lesions typical of C. hepaticum. Light microscopy of fresh samples and
      histological specimens permitted the identification of larvae and adult specimens
      containing numerous eggs with a double-striated shell and bipolar opercula with
      plugs. This is the first report of C. hepaticum in R. rattus and R. norvegicus
      from the Amazon Basin, and it shows a considerable risk of transmission to the
      local human population. 

PMID- 23856731
TI  - Susceptibility of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) to
      pyrethroids and their associations in Pernambuco, Brazil.
AB  - The synthetic pyrethroids and their associations have been widely used for
      controlling Rhipicephalus (Boophilus) microplus. The frequent use of acaricides
      has been inducing the development of resistance in the tick populations. The aim
      of this study was to assess the susceptibility of R. (B.) microplus populations
      to pyrethroids and their associations in the region of Garanhuns, Pernambuco,
      Brazil. In addition, the level of information among farm owners regarding tick
      control measures was investigated. Ticks were collected directly from naturally
      infested dairy cattle in the region and were exposed to pyrethroids and their
      associations. At the same time, an epidemiological questionnaire was applied with
      the aim of investigating the level of information among the farmers. The results
      reported here indicate that R. (B.) microplus populations in the dairy region of
      Garanhuns show resistance to pyrethroids and their associations, except when the
      product is associated with piperonyl butoxide. Regarding the results from the
      epidemiological survey, it was seen that there is a considerable lack of
      information among the farmers in relation to ixodid control measures. The level
      of ticks resistance to acaricides varied widely across the region studied. No
      alternative control programs have been implemented among these farms, thus
      demonstrating that there is a need for more information relating to the biology
      and control of R. (B.) microplus. 

PMID- 23856732
TI  - Histopathological findings of the kidney Trematoda Paratanaisia spp. (Digenea:
      Eucotylidae) in cattle egret (Bubulcus ibis).
AB  - Paratanaisia spp. was recorded from the right kidney of a cattle egret (Bubulcus
      ibis) in Kafr Elsheikh governorate, Nile Delta, Egypt. The bird showed marked
      emaciation and dissipation. Necropsy findings revealed marked enlargement and
      brownish discoloration of the kidney. Microscopic examination demonstrated marked
      dilatation of renal tubules with hyperplasia of lining epithelium due to presence
      of a trematode consistent with Paratanaisia spp. Eggs of this parasite were also
      noticed deeply within the interstitial tissue, surrounded with mononuclear cell
      infiltration, thus indicating their pathogenic potential. This result is the
      first report of trematodes of this genus parasitizing the kidneys of cattle
      egrets. 

PMID- 23856733
TI  - Immune response of calves inoculated with proteins of Anaplasma marginale bound
      to an immunostimulant complex.
AB  - Despite our current knowledge of the immunology, pathology, and genetics of
      Anaplasma marginale, prevention in cattle is currently based on old standbys,
      including live attenuated vaccines, antibiotic treatment, and maintaining
      enzootic stability in cattle herds. In the present study, we evaluated the use of
      an immunostimulant complex (ISCOMATRIX) adjuvant, associated with a pool of
      recombinant major surface proteins (rMSP1a, rMSP1b, rMSP4 and rMSP5) to improve
      the humoral immune response triggered in calves mainly by IgG2. Ten calves were
      divided in three groups: 4 calves were inoculated with the ISCOMATRIX/rMSPs (G1);
      2 calves were inoculated with ISCOMATRIX adjuvant (G2); and 4 calves received
      saline (G3). Three inoculations were administered at 21-day intervals. In G1, the
      calves showed significant increases in total IgG, IgG1 and IgG2 levels 21 days
      after the second inoculation, compared to the control group (p < 0.05), and G1
      calves remained above the cut-off value 28 days after the third inoculation (p <
      0.05). The post-immunized sera from calves in G1 reacted specifically for each of
      the rMSPs used. In conclusion, the ISCOMATRIX/rMSPs induced antigen-specific
      seroconversion in calves. Therefore, additional testing to explore the protection
      induced by rMSPs, both alone and in conjunction with proteins previously
      identified as subdominant epitopes, is warranted. 

PMID- 23856734
TI  - Transplacental transmission of Anaplasma marginale in beef cattle chronically
      infected in southern Brazil.
AB  - In this study, we have investigated the incidence of transplacental transmission
      of Anaplasma marginale in chronically infected cows with no history of acute
      anaplasmosis during gestation. In addition, we evaluated various techniques for
      detection of transplacental transmission of A. marginale. Blood samples were
      collected from 30 cows at three different periods: at the time of artificial
      insemination, at gestational diagnosis, and after calving. Also, blood was
      collected from the newborn calves, including one sample before colostrum intake,
      and another three days after birth. A. marginale-specific antibodies were
      detected in 100% of the cows with an indirect fluorescent antibody test (IFAT),
      and in 97% of them, using an indirect enzyme-linked immunosorbent assay (ELISA).
      Also, we observed that all of the three-day-old newborn calves were seropositive
      by IFAT. According to polymerase chain reaction, 63.3% of the cows were carriers
      of A. marginale, as well as 6.7% of the newborn calves. This represented a
      transplacental transmission rate of 10.5%. Furthermore, a correlation of 93.3%
      was observed between the two serodiagnostic techniques, demonstrating that both
      ELISA and IFAT can be used in epidemiological surveys of A. marginale. These
      results confirm the occurrence of transplacental transmission of A. marginale in
      chronically infected cows and suggest the importance of this transmission route
      in areas of enzootic instability. 

PMID- 23856735
TI  - Prevalence and risk factors associated to ovine toxoplasmosis in northeastern
      Brazil.
AB  - In this study, we aimed to determine the prevalence and risk factors associated
      to Toxoplasma gondii infection in sheep from northeastern Brazil. A total of 932
      ovine serum samples from 54 properties in 19 municipalities of the state of
      Sergipe were collected and assayed using indirect fluorescent antibody test. The
      assay used antibodies against Toxoplasma gondii (IFAT-IgG) with a cutoff point of
      1:64. We observed that 28.22% (263/932) of the ovine samples were serum-reactive.
      In a logistic regression, factors such as consumption of water directly from the
      source, consumption of water from a deep well, and age below 12 months were
      associated with protection; whereas factors such as presence of cats on the
      property, presence of slatted floor, and use of exchanged or borrowed breeding
      males were associated with infection. The studied area can be considered endemic
      for toxoplasmosis, so it is necessary to adopt preventive and control measures
      because this zoonotic infection poses risks to public health. 

PMID- 23856736
TI  - Optimization of protease production by the fungus Monacrosporium thaumasium and
      its action against Angiostrongylus vasorum larvae.
AB  - The objectives of this study were to optimize protease production from the
      nematophagous fungus Monacrosporium thaumasium (NF34a) and evaluate its
      larvicidal activity and biological stability. An isolate of the nematophagous
      fungus Monacrosporium thaumasium (NF34a) was used to produce the enzyme. The
      Plackett-Burman design was used in order to scan which components of the culture
      medium could have a significant influence on protease production by the fungus
      NF34a. An in vitro assay was also performed to evaluate the larvicidal activity
      of NF34a. It was observed that only one component of the culture medium (yeast
      extract), at the levels studied, had any significant effect (p < 0.05) on
      protease production. There was a reduction (p < 0.01) in the mean number of
      larvae recovered from the treated groups, compared with the control groups. The
      results confirm previous reports on the efficiency of nematophagous fungi for
      controlling nematode larvae that are potentially zoonotic. Thus, given the
      importance of biological control, we suggest that further studies should be
      conducted on the protease produced by the fungus Monacrosporium thaumasium. 

PMID- 23856737
TI  - Survey of helminth parasites of cats from the metropolitan area of Cuiaba, Mato
      Grosso, Brazil.
AB  - Besides presenting zoonotic potential, helminths of cats are responsible for
      gastrointestinal, hepatic, and pulmonary diseases. In order to identify the
      helminthic fauna, prevalence, mean intensity of parasitism (MIP), and mean
      abundance population (MAP), 146 cats from the metropolitan area of Cuiaba,
      Midwestern Brazil, were necropsied. In 98 these animals, 12 species of helminths
      were identified, comprising (species, prevalence, MIP, and MAP, respectively):
      nematodes (Ancylostoma braziliense [50,68% - 53,64 - 27,18], Ancylostoma
      tubaeforme [10,27% - 3,6 - 0,37], Toxocara cati [4,11% - 28,33 - 1,16],
      Physaloptera praeputialis [2,05% - 6,67 - 0,14], Capillaria feliscati [3,42% -
      7,4 - 0,25], and Aelurostrongylus abstrusus [1,37%]); cestodes (Spirometra
      mansonoides [4,11% - 2,0 - 0,08], Dipylidium caninum [3,42% - 5,2 - 0,18], and
      Taenia taeniformis [0,68% - 1,0 - 0,01]); trematodes (Platynosomum fastosum
      [26,03% - 179,53 - 46,73]); acanthocephalans (Centrorhynchus erraticus [3,42% -
      3,2 - 0,11]). Ancylostoma spp., and P. fastosum were the most prevalent with the
      highest MIP and MAP. We observed the presence of species of helminths with
      zoonotic potential. This is the first time cats parasitized with Centrorhynchus
      erraticus are reported in the Americas. That genus is commonly observed in wild
      animals. 

PMID- 23856738
TI  - Parasites of Psittaciformes and Accipitriformes in Paraiba state, northeastern
      Brazil.
AB  - In this study, we investigated the presence of gastrointestinal helminths in 97
      captive birds (Psittaciformes and Accipitriformes) necropsied between June and
      December 2011 in the state of Paraiba, Brazil. Forty-three birds were infected.
      Psittaciformes were infected by nematode Ascaridia hermaphrodita (97.6%) and
      cestode Raillietina sp. (2.4%). A. hermaphrodita was found in all species of
      parrots and Raillietina sp. was found only in Amazona aestiva. A. hermaphrodita
      was the cause of death, by intestinal obstruction, in 14 of the 40 birds
      investigated. Accipitriformes were infected by nematode Synhimantus (Synhimantus)
      rectus (100%) and acantocephalan Centrorhynchus tumidulus (50%). In Brazil,
      Diopsittaca nobilis and A. aestiva are reported for the first time as hosts of A.
      hermaphrodita and Raillietina sp., respectively. We concluded that Psittaciformes
      and Accipitriformes in captivity are affected by nematodes, cestodes and
      acanthocephalans and that implementation of control measures is essential. 

PMID- 23856739
TI  - Fecal occult blood test and colorectal cancer: validation study with special
      reference to false-negative patients.

PMID- 23856740
TI  - Immunogenicity of subcutaneously administered therapeutic proteins--a mechanistic
      perspective.
AB  - The administration of therapeutic proteins via the subcutaneous route (sc) is
      desired for compliance and convenience, but could be challenging due to perceived
      immunogenic potential or unwanted immune responses. There are clinical and
      preclinical data supporting as well as refuting the generalized notion that sc is
      more immunogenic. We provide a mechanistic perspective of immunogenicity of
      therapeutic proteins administered via the sc route and discuss strategies and
      opportunities for novel therapeutic approaches to mitigate immunogenicity. 

PMID- 23856741
TI  - Genetic map of the primocane-fruiting and thornless traits of tetraploid
      blackberry.
AB  - Blackberry primocane fruiting, fruiting on first-year canes, has the potential to
      expand blackberry production both seasonally and geographically. The
      incorporation of the primocane-fruiting trait into cultivars with desirable
      horticultural attributes is challenging due to its recessive nature and
      tetrasomic inheritance. Molecular marker-assisted selection has high potential to
      facilitate incorporation, because breeders already use morphological marker
      assisted selection of seedlings without marginal cotyledonary hairs to identify
      progeny that will be thornless when mature. The development of a genetic linkage
      map with these two traits is the first step to utilizing molecular markers in
      breeding for thornless primocane-fruiting blackberry cultivars. A full-sib family
      segregating for thornlessness and primocane fruiting, from a cross between 'APF
      12' and 'Arapaho', was used to construct the first genetic map of tetraploid
      blackberry. Segregation patterns of several dominant markers and the two
      phenotypic traits fit those expected uniquely with tetrasomic inheritance (e.g.,
      5:1, 11:1 and 35:1). Some loci showed significant double reduction frequencies,
      but genotypes that could have originated only from double reduction were not
      found. The map consists of seven linkage groups (LG) in each parent, consistent
      with the basic number of chromosomes (2n = 4x = 28). Naming of LG1-LG6 followed
      that of the recently revised system for raspberry using SSR markers in common
      between blackberry and raspberry, and LG7 was tentatively defined by default. The
      loci controlling primocane fruiting and thornlessness were not linked to each
      other; thornless/thorny, the S Locus, was mapped on LG4, and the primocane
      /floricane-fruiting locus, named in this work the F Locus, on LG7. 

PMID- 23856742
TI  - Immobilization of lead in contaminated firing range soil using biochar.
AB  - Soybean stover-derived biochar was used to immobilize lead (Pb) in military
      firing range soil at a mass application rate of 0 to 20 wt.% and a curing period
      of 7 days. The toxicity characteristic leaching procedure (TCLP) was performed to
      evaluate the effectiveness of the treatment. The mechanism responsible for Pb
      immobilization in military firing range soil was evaluated by scanning electron
      microscopy-energy dispersive x-ray spectroscopy (SEM-EDX) and x-ray absorption
      fine structure (XAFS) spectroscopy analyses. The treatment results showed that
      TCLP Pb leachability decreased with increasing biochar content. A reduction of
      over 90 % in Pb leachability was achieved upon treatment with 20 wt.% soybean
      stover-derived biochar. SEM-EDX, elemental dot mapping and XAFS results in
      conjunction with TCLP leachability revealed that effective Pb immobilization was
      probably associated with the pozzolanic reaction products, chloropyromorphite and
      Pb-phosphate. The results of this study demonstrated that soybean stover-derived
      biochar was effective in immobilizing Pb in contaminated firing range soil.

PMID- 23856743
TI  - Effective utilization of dichloromethane by a newly isolated strain
      Methylobacterium rhodesianum H13.
AB  - An effective dichloromethane (DCM) utilizer Methylobacterium rhodesianum H13 was
      isolated from activated sludge. A response surface methodology was conducted, and
      the optimal conditions were found to be 4.5 g/L Na2HPO4.12H2O, 0.5 g/L (NH4)2SO4,
      an initial pH of 7.55, and a temperature of 33.7  degrees C. The specific growth
      rate of 0.25 h(-1) on 10 mM DCM was achieved, demonstrating that M. rhodesianum
      H13 was superior to the other microorganisms in previous investigations of DCM
      utilization. DCM mineralization paralleled the production of cells, CO2, and
      water-soluble metabolites, as well as the release of Cl(-), whereas the carbon
      distribution and Cl(-) yield varied with DCM concentrations. The facts that
      complete degradation only occurred with DCM concentrations below 15 mM and
      repetitive degradation of 5 mM DCM could proceed for only three cycles were
      ascribed to pH decrease (from 7.55 to 3.02) though a buffer system was employed.

PMID- 23856744
TI  - Chemotherapy dosing in overweight and obese patients with cancer.
AB  - Retrospective and prospective preclinical and clinical data have demonstrated an
      association between chemotherapy dose intensity and both clinical efficacy and
      toxicity. The optimum tolerable and effective dose and schedule of
      chemotherapeutic agents is based on data from dose-finding studies and early
      clinical trials. There is considerable evidence that reductions in the
      recommended dose intensity often occurs in actual clinical practice, particularly
      among overweight and obese patients with cancer. With increasing rates of
      obesity, and variation and uncertainty about appropriate dosing of chemotherapy
      in obese patients, ASCO has generated clinical practice guidelines for
      appropriate chemotherapy dosing for obese adult patients with cancer. Without
      evidence of any increase in treatment-related toxicity among obese patients
      receiving chemotherapy, the guidelines recommend that, after considering any
      accompanying comorbidities, chemotherapy dosing should be calculated based on
      body surface area using actual weight, rather than an estimate or idealization of
      weight. While further research is needed, pharmacokinetic studies support the use
      of actual body weight to calculate chemotherapy doses for most chemotherapy drugs
      in obese patients. We highlight the issue of chemotherapy dosing in this
      population, how a more personalized approach can be achieved, as well as
      discussing areas for further research. 

PMID- 23856747
TI  - Imaging: Novel glucose uptake imaging method.

PMID- 23856749
TI  - Targeted therapies: the maths behind combination therapy.

PMID- 23856752
TI  - Atomic level observation of octahedral distortions at the perovskite oxide
      heterointerface.
AB  - For perovskite oxides, ABO3, slight octahedral distortions have close links to
      functional properties. While perovskite oxide heterostructures offer a good
      platform for controlling functionalities, atomistic understanding of octahedral
      distortion at the interface has been a challenge as it requires precise
      measurements of the oxygen atomic positions. Here we demonstrate an approach to
      clarify distortions at an atomic level using annular bright-field imaging in
      aberration-corrected scanning transmission electron microscopy, which provides
      precise mappings of cation and oxygen atomic positions from distortion-minimized
      images. This technique revealed significant distortions of RuO6 and ScO6
      octahedra at the heterointerface between a SrRuO3 film and a GdScO3 substrate. We
      also found that structural mismatch was relieved within only four unit cells near
      the interface by shifting the oxygen atomic positions to accommodate octahedral
      tilt angle mismatch. The present results underscore the critical role of the
      oxygen atom in the octahedral connectivity at the perovskite oxide
      heterointerface. 

PMID- 23856746
TI  - Clinical management of obese patients with cancer.
AB  - A large body of epidemiological evidence links obesity to increased cancer
      incidence, with some studies also indicating poorer survival in obese patients
      with cancer. Obese patients face several specific challenges related to diagnosis
      and treatment of cancer. Reduced participation in cancer screening programmes,
      lower tumour-marker expression and issues with medical imaging among obese
      individuals complicate cancer diagnosis. Chemotherapy and hormonal therapy in
      obese patients with cancer is affected by altered pharmacokinetics and hormone
      levels. In addition, the precision of radiotherapy might be adversely affected in
      this population by greater skin motility and increased motion of internal organs.
      Obese patients also face higher risk of minor complications after surgery. There
      is a need for additional research addressing issues specifically associated with
      the clinical management of obese patients with cancer, including comorbidity,
      polypharmacy, and problems related to sarcopenia and health-related quality of
      life. This Review summarizes the available literature addressing the clinical
      management of obese patients with cancer and discusses opportunities to improve
      the cancer care of these patients. 

PMID- 23856753
TI  - Outcome of single-stage breast reconstruction using the Natrelle 150 expander
      implant.
AB  - The Natrelle 150 offers the advantage of single-stage reconstruction. However,
      there is lack of published data on its long term outcomes, which does not allow
      for definitive conclusions as to whether it truly meets its design objective of a
      lasting single stage breast reconstruction. This is a retrospective review of all
      Natrelle 150 reconstructions by a single surgeon over 5 years. A total of 143
      procedures were performed in 125 patients with a mean follow-up of 33 months
      (range, 3-65 months). Most (120, 84%) received the implant after oncological
      mastectomies, 22 (15%) after risk-reducing mastectomies, and 1 (0.8%) for
      hypoplasia. Fifty-one (35.7%) implants were explanted an average of 12.9 months
      after implantation. A Kaplan-Meier survival analysis demonstrates an explantation
      rate of 25% by 11 months. Explantation was more likely after subpectoral
      placement compared to reconstructions in combination with latissimus dorsi flaps
      (P<0.05). Risk-reducing reconstructions were also more likely to undergo
      explantation (P<0.05) compared to reconstructions for oncological reasons. Our
      data suggest that this prosthesis is only successful as a 1-stage procedure in
      certain patients, and has led to more careful patient selection and counseling.

PMID- 23856755
TI  - Palladium-catalyzed desulfitative hydroarylation of alkynes with sodium
      sulfinates.
AB  - A palladium-catalyzed desulfitative hydroarylation of alkynes with aryl sulfinic
      acid sodium salts is described. The reaction showed good regio- and
      stereoselectivity, and afforded the hydroarylation products in good yields.
      Various functional groups were well tolerated under the optimized reaction
      conditions. 

PMID- 23856754
TI  - Effects of fetal exposure to maternal chemotherapy.
AB  - Approximately 1 in 1,000-2,000 pregnancies are complicated by cancer. Today,
      different treatment options are considered as safe during pregnancy:
      chemotherapy, radiotherapy, surgery, or a combination of these. Surgery is
      considered safe during all trimesters of pregnancy; radiotherapy can be
      administered during the first and the second trimester, and chemotherapy after
      the first trimester of pregnancy. The placenta, acting as a barrier between the
      mother and the fetus, plays a key role in the safe administration of chemotherapy
      during pregnancy. A few studies have investigated the short- as well as the long
      term health, general development, and cognitive and cardiac outcomes on children
      exposed to chemotherapy in utero. In general, these results were reassuring.
      Nevertheless, better safety data are required. This means data with longer follow
      up periods and comparison with appropriate control groups. Moreover, important
      biasing factors should be taken into account when interpreting these results.
      Firstly, a great proportion of children were born prematurely due to the maternal
      condition. Preterm birth in general has been associated with cognitive
      impairment. Secondly, cancer during pregnancy is clearly a stressful situation,
      and maternal stress is associated with attention deficits. In sum, we state that
      chemotherapy can be administered safely after the first trimester of pregnancy.
      Moreover, iatrogenic prematurity in order to start postpartum administration of
      chemotherapy should be avoided. Nonetheless, decisions concerning treatment in
      these specific cases should always be made in a multidisciplinary setting with
      internationally recognized expertise in the coexistence of cancer and pregnancy. 

PMID- 23856756
TI  - Thin film formation of platinum nanoparticles at oil-water interface, using
      organoplatinum(II) complexes, suitable for electro-oxidation of methanol.
AB  - A simple and effective strategy is presented to integrate individual platinum
      nanoparticles (NPs) into macroscopic thin films based on the reduction of
      organoplatinum(II) complexes [PtCl2(cod)] 1a, [PtI2(cod)] 1b (cod = 1,5
      cyclooctadiene) and cis-[Pt(p-MeC6H4)2(SMe2)2] 2, at the toluene-water interface
      in the absence of stabilizer. Structure and morphology of the platinum NPs were
      characterized with X-ray diffraction (XRD), transmission electron microscopy
      (TEM), and selected area electron diffraction (SAED) techniques. Finally,
      platinum thin films were deposited on glassy carbon electrode and their electro
      oxidation was investigated in the methanol oxidation reaction. Pt NPs thin films
      showed highly improved electrocatalytical activity toward methanol oxidation as
      compared with commercial platinum catalysts. The present method provides a facile
      and low-cost strategy toward the synthesis of different electrocatalysts of noble
      metals for application in fuel cells.

PMID- 23856757
TI  - High-throughput deterministic single-cell encapsulation and droplet pairing,
      fusion, and shrinkage in a single microfluidic device.
AB  - In this article, we present a microfluidic device capable of successive high
      yield single-cell encapsulation in droplets, with additional droplet pairing,
      fusion, and shrinkage. Deterministic single-cell encapsulation is realized using
      Dean-coupled inertial ordering of cells in a Yin-Yang-shaped curved microchannel
      using a double T-junction, with a frequency over 2000 Hz, followed by controlled
      droplet pairing with a 100% success rate. Subsequently, droplet fusion is
      realized using electrical actuation resulting in electro-coalescence of two
      droplets, each containing a single HL60 cell, with 95% efficiency. Finally,
      volume reduction of the fused droplet up to 75% is achieved by a triple pitchfork
      structure. This droplet volume reduction is necessary to obtain close cell-cell
      membrane contact necessary for final cell electrofusion, leading to hybridoma
      formation, which is the ultimate aim of this research. 

PMID- 23856758
TI  - Crescentic glomerulonephritis in a polar bear (Ursus maritimus).
AB  - Spontaneous crescentic glomerulonephritis (CrGN) in animals has only been
      reported in dog and sheep. We report the pathological features of CrGN in a 17
      year-old male polar bear that died due to renal failure. Histologically, the
      lesions were characterized by fibrocellular crescents, adhesion between Bowman's
      capsule and the glomerular capillary tuft and an increase in the mesangial matrix
      in glomeruli. The proliferating cells in the crescent were partly immunopositive
      for cytokeratin and intensely positive for vimentin, WT-1 and alpha-smooth muscle
      actin, suggesting they originated from parietal epithelial cells.
      Ultrastructually, thickening of the glomerular basement membrane and loss of
      epithelial cell foot processes were observed with electron-dense deposits. 

PMID- 23856759
TI  - Detection of aac(6')-Ib-cr in avian pathogenic Escherichia coli isolates in
      Japan.
AB  - We investigated the prevalence of plasmid-mediated quinolone resistance (PMQR)
      genes in avian pathogenic Escherichia coli (APEC) strains in Japan. A total of
      117 APEC strains collected between 2004 and 2007 were examined for PMQR genes
      (qnrA, qnrB, qnrC, qnrD, qnrS, aac(6')-Ib-cr, qepA and oqxAB) by polymerase chain
      reaction. None of the APEC strains carried qnrA, qnrB, qnrC, qnrD, qnrS, qepA or
      oqxAB, but one of the isolates was identified as an AAC (6')-Ib-cr producer.
      Phylogenetic grouping, multi-locus sequence typing and serotyping showed that
      this isolate belonged to phylogenetic group A, sequence type 167 and untypable
      serogroup. To our knowledge, this is the first report of the aac (6')-Ib-cr gene
      in bacteria from food-producing animals in Japan. 

PMID- 23856761
TI  - Serum glial fibrillary acidic protein as a specific marker for necrotizing
      meningoencephalitis in Pug dogs.
AB  - To evaluate the ability of serum glial fibrillary acidic protein (GFAP)
      concentration as a diagnostic marker for canine central nervous system (CNS)
      disorders, sera from dogs with various CNS (n=47) and non-CNS (n=56) disorders
      were measured for GFAP by using an ELISA kit. Healthy Beagles (n=15) and Pug dogs
      (n=12) were also examined as controls. Interestingly, only Pug dogs with
      necrotizing meningoencephalitis (NME) showed elevated serum GFAP concentrations
      (<0.01 to 1.14 ng/ml), while other breeds of dogs with NME did not. Among the Pug
      dogs with NME, serum GFAP concentrations did not correlate with their clinical
      features, such as ages or survival times. Our data indicate the usefulness of
      serum GFAP as a novel marker for Pug dogs with NME. 

PMID- 23856760
TI  - The genetic diversity of merozoite surface antigen 1 (MSA-1) among Babesia bovis
      detected from cattle populations in Thailand, Brazil and Ghana.
AB  - In the present study, we screened blood DNA samples obtained from cattle bred in
      Brazil (n=164) and Ghana (n=80) for Babesia bovis using a diagnostic PCR assay
      and found prevalences of 14.6% and 46.3%, respectively. Subsequently, the genetic
      diversity of B. bovis in Thailand, Brazil and Ghana was analyzed, based on the
      DNA sequence of merozoite surface antigen-1 (MSA-1). In Thailand, MSA-1 sequences
      were relatively conserved and found in a single clade of the phylogram, while
      Brazilian MSA-1 sequences showed high genetic diversity and were dispersed across
      three different clades. In contrast, the sequences from Ghanaian samples were
      detected in two different clades, one of which contained only a single Ghanaian
      sequence. The identities among the MSA-1 sequences from Thailand, Brazil and
      Ghana were 99.0-100%, 57.5-99.4% and 60.3-100%, respectively, while the
      similarities among the deduced MSA-1 amino acid sequences within the respective
      countries were 98.4-100%, 59.4-99.7% and 58.7-100%, respectively. These
      observations suggested that the genetic diversity of B. bovis based on MSA-1
      sequences was higher in Brazil and Ghana than in Thailand. The current data
      highlight the importance of conducting extensive studies on the genetic diversity
      of B. bovis before designing immune control strategies in each surveyed country. 

PMID- 23856762
TI  - PCR detection and genetic diversity of bovine hemoprotozoan parasites in Vietnam.
AB  - Hemoprotozoan infections often cause serious production losses in livestock. In
      the present study, we conducted a PCR-based survey of Babesia bovis, Babesia
      bigemina, Theileria annulata, Theileria orientalis, Trypanosoma evansi and
      Trypanosoma theileri, using 423 DNA samples extracted from blood samples of
      cattle (n=202), water buffaloes (n=43), sheep (n=51) and goats (n=127) bred in
      the Hue and Hanoi provinces of Vietnam. With the exception of T. annulata and T.
      evansi, all other parasite species (B. bovis, B. bigemina, T. orientalis and T.
      theileri) were detected in the cattle populations with B. bovis being the most
      common among them. Additionally, four water buffaloes and a single goat were
      infected with B. bovis and B. bigemina, respectively. The Hue province had more
      hemoprotozoan-positive animals than those from the Hanoi region. In the
      phylogenetic analyses, B. bovis-MSA-2b, B. bigemina-AMA-1 and T. theileri-CATL
      gene sequences were dispersed across four, one and three different clades in the
      respective phylograms. This is the first study in which the presence of Babesia,
      Theileria and Trypanosoma parasites was simultaneously investigated by PCR in
      Vietnam. The findings suggest that hemoprotozoan parasites, some of which are
      genetically diverse, continue to be a threat to the livestock industry in this
      country. 

PMID- 23856763
TI  - A dual electrochemical microsensor for simultaneous imaging of oxygen and pH over
      the rat kidney surface.
AB  - In this study, a dual microsensing electrochemical probe for measuring oxygen
      (O2) and pH levels was developed based on a dual recessed Pt disk electrode (each
      disk diameter, 10 MUm) with the use of two Ag/AgCl reference electrodes (one for
      each disk of the dual electrode). One of the recessed Pt disks of the dual
      electrode was electrodeposited with a porous Pt layer and then coated with a
      hydrophobic photocured polymer (partially fluorinated epoxy diacrylate,
      abbreviated as FED). The Pt-FED covered disk was used as an amperometric O2
      sensor and exhibited a linear current increase that was proportional to the PO2
      level (partial O2 pressure) with high sensitivity (168.4 +/- 33.8 pA mmHg(-1))
      and fast response time (t90% = 0.17 +/- 0.05 s). The other recessed Pt disk was
      electrodeposited with an IrO2 layer. The potential between the IrO2 deposited
      electrode and the Ag/AgCl reference electrode produced a reliable Nernstian
      response to pH changes (58.3 +/- 1.5 mV pH(-1)) with a t90% of 0.43 +/- 0.09 s.
      The sensor displayed high stability in the in vitro organ tissue measurements for
      at least 2.5 h. By using the developed dual O2/pH microsensor as a probe tip for
      scanning electrochemical microscopy, the two-dimensional images of the location
      dependent PO2 and pH levels were simultaneously acquired and could be used to
      assess the surface of a rat kidney tissue slice. When compared to the
      corresponding medullary levels, both PO2 and pH were observed to be higher in the
      cortex area, while the modest level gradient was observed near the cortex-medulla
      border. This finding suggests that there is a direct relationship between the
      tissue O2 supply/consumption and pH, which is mainly determined by metabolite,
      such as CO2, production. 

PMID- 23856764
TI  - Impairment-driven cancer rehabilitation: an essential component of quality care
      and survivorship.
AB  - Adult cancer survivors suffer an extremely diverse and complex set of
      impairments, affecting virtually every organ system. Both physical and
      psychological impairments may contribute to a decreased health-related quality of
      life and should be identified throughout the care continuum. Recent evidence
      suggests that more cancer survivors have a reduced health-related quality of life
      as a result of physical impairments than due to psychological ones. Research has
      also demonstrated that the majority of cancer survivors will have significant
      impairments and that these often go undetected and/or untreated, and consequently
      may result in disability. Furthermore, physical disability is a leading cause of
      distress in this population. The scientific literature has shown that
      rehabilitation improves pain, function, and quality of life in cancer survivors.
      In fact, rehabilitation efforts can ameliorate physical (including cognitive)
      impairments at every stage along the course of treatment. This includes
      prehabilitation before cancer treatment commences and multimodal
      interdisciplinary rehabilitation during and after acute cancer treatment.
      Rehabilitation appears to be cost-effective and may reduce both direct and
      indirect health care costs, thereby reducing the enormous financial burden of
      cancer. Therefore, it is critical that survivors are screened for both
      psychological and physical impairments and then referred appropriately to trained
      rehabilitation health care professionals. This review suggests an impairment
      driven cancer rehabilitation model that includes screening and treating
      impairments all along the care continuum in order to minimize disability and
      maximize quality of life.

PMID- 23856765
TI  - Thymic epithelial beta-catenin is required for adult thymic homeostasis and
      function.
AB  - The role of beta-catenin in thymocyte development has been extensively studied,
      however, the function of beta-catenin in thymic epithelial cells (TECs) remains
      largely unclear. Here, we demonstrate a requirement for beta-catenin in keratin 5
      (K5)-expressing TECs, which comprise the majority of medullary TECs (mTECs) and a
      progenitor subset for cortical TECs (cTECs) in the young adult thymus. We found
      that conditionally ablated beta-catenin in K5(+)-TECs and their progeny cells
      resulted in thymic atrophy. The composition of TECs was also aberrantly affected.
      Percentages of K5(hi)K8(+)-TECs, K5(+)K8(-)-TECs and UEA1(+)-mTECs were
      significantly decreased and the percentage of K5(lo)K8(+)-TECs and Ly51(+)-cTECs
      were increased in beta-catenin-deficient thymi compared with that in the control
      thymi. We also observed that beta-catenin-deficient TEC lineage could give rise
      to K8(+)-cTECs more efficiently than wild-type TECs using lineage-tracing
      approach. Importantly, the expression levels of several transcription factors
      (p63, FoxN1 and Aire), which are essential for TEC differentiation, were altered
      in beta-catenin-deficient thymi. Under the aberrant differentiation of TECs,
      development of all thymocytes in beta-catenin-deficient thymi was impaired.
      Interleukin-7 (IL-7) and chemokines (Ccl19, Ccl25 and Cxcl12) levels were also
      downregulated in the thymic stromal cells in the mutants. Finally, introducing a
      BCL2 transgene in lymphoid lineages, which has been shown to rescue IL-7
      deficient thymopoiesis, partially rescued the thymic atrophy and thymocyte
      development defects caused by induced ablation of beta-catenin in K5(+)-TECs.
      Collectively, these findings suggest that beta-catenin is required for the
      differentiation of TECs, thereby contributing to thymocyte development in the
      postnatal thymus. 

PMID- 23856766
TI  - The developing schistosome worms elicit distinct immune responses in different
      tissue regions.
AB  - Schistosome parasites follow a complex migration path through various tissues,
      changing their antigenic profile as they develop. A thorough understanding of the
      antibody response in each tissue region could help unravel the complex immunology
      of these developing parasites and aid vaccine design. Here we used a novel
      strategy for analysing the local antibody responses induced by Schistosoma
      japonicum infection at each site of infection. Cells from rat lymph nodes
      draining the sites of larval migration (the skin and lungs), the liver-lymph
      nodes where adults reside and the spleens were cultured to allow the in vivo
      induced antibody-secreting cells to release antibody into the media. The amount
      and isotype of antibodies secreted in the supernatants differed significantly in
      the different lymph nodes and spleen, corresponding with the migration path of
      the schistosome worms. In addition, there were significant differences in binding
      specificity, as determined by surface labelling, western blots and by screening a
      glycan array. Through capturing the local antibody response, this study has
      revealed dramatic differences in the quality and specificity of the immune
      response at different tissue sites, and highlighted the existence of stage
      specific protein and carbohydrate antigens. This will provide a valuable tool for
      the isolation of novel vaccine targets against the larval stages of schistosomes.

PMID- 23856767
TI  - Cost-effectiveness analysis comparing two approaches for empirical antifungal
      therapy in hematological patients with persistent febrile neutropenia.
AB  - New approaches of empirical antifungal therapy (EAT) in selected hematological
      patients with persistent febrile neutropenia (PFN) have been proposed in recent
      years, but their cost-effectiveness has not been studied. The aim of this study
      was to compare the cost-effectiveness of two different approaches of EAT in
      hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT)
      approach versus the standard approach of EAT. A decision tree to assess the cost
      effectiveness of both approaches was developed. Outcome probabilities and
      treatment pathways were extrapolated from two studies: a prospective cohort study
      following the DDAT approach and a randomized clinical trial following the
      standard approach. Uncertainty was undertaken through sensitivity analyses and
      Monte Carlo simulation. The average effectiveness and economic advantages in the
      DDAT approach compared to the standard approach were 2.6% and ?5,879 (33%) per
      PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the
      simulations performed with average cost-effectiveness per PFN episode of ?32,671
      versus ?52,479 in the EAT approach. The results were robust over a wide range of
      variables. The DDAT approach is more cost-effective than the EAT approach in the
      management of PFN in hematological patients. 

PMID- 23856768
TI  - Amphotericin B- and voriconazole-echinocandin combinations against Aspergillus
      spp.: Effect of serum on inhibitory and fungicidal interactions.
AB  - Antifungal combination therapy with voriconazole or amphotericin B and an
      echinocandin is often employed as primary or salvage therapy for management
      particularly of refractory aspergillosis. The pharmacodynamic interactions of
      amphotericin B- and voriconazole-based combinations with the three echinocandins
      caspofungin, micafungin, and anidulafungin in the presence of serum were tested
      against 15 Aspergillus fumigatus complex, A. flavus complex, and A. terreus
      complex isolates to assess both their growth-inhibitory and fungicidal
      activities. The in vitro activity of each drug alone and in combination at a 1:1
      fixed concentration ratio was tested with a broth microdilution colorimetric
      method, and interactions were assessed by isobolographic analysis. Synergy was
      found for all amphotericin B- and voriconazole-based combinations, with
      amphotericin B-based combinations showing strong inhibitory synergistic
      interactions (interaction indices of 0.20 to 0.52) and with voriconazole-based
      combinations demonstrating strong fungicidal synergistic interactions
      (interaction indices of 0.10 to 0.29) (P < 0.001). Drug- and species-specific
      differences were found, with caspofungin and the A. fumigatus complex exhibiting
      the weakest synergistic interactions. In the presence of serum, the synergistic
      interactions were reduced in the order (from largest to smallest decrease)
      micafungin > anidulafungin > caspofungin, and A. flavus complex > A. fumigatus
      complex > A. terreus complex, resulting in additive interactions, particularly
      for inhibitory activities of amphotericin B-echinocandin combinations and
      fungicidal activities of voriconazole-echinocandin combinations. Drug- and
      species-specific differences were found in the presence of serum for inhibitory
      activities of antifungal drugs, with the lowest interaction indices being
      observed for amphotericin B-caspofungin (median, 0.77) and for the A. terreus
      complex (median, 0.56). The present in vitro data showed that serum had a major
      impact on synergistic interactions of amphotericin B-echinocandin and
      voriconazole-echinocandin combinations, resulting in additive interactions and
      explaining the indifferent outcomes usually observed in vivo. 

PMID- 23856769
TI  - KPC-producing, multidrug-resistant Klebsiella pneumoniae sequence type 258 as a
      typical opportunistic pathogen.
AB  - The virulence of a KPC-producing Klebsiella pneumoniae sequence type 258 (ST258)
      strain representing those circulating in Greece was assessed in a mouse
      septicemia model. The strain was virtually avirulent (50% lethal dose, >10(8) and
      5 * 10(7) CFU for immunocompetent and neutropenic animals, respectively). Also,
      it was highly susceptible to serum killing, rapidly phagocytosed in vitro, and
      classified as K41, which is not among the virulent capsular types. The findings
      indirectly support the notion that high ST258-associated mortality is largely due
      to inefficient antimicrobial treatment. 

PMID- 23856770
TI  - Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis
      inhibitor salicyl-AMS in mice.
AB  - Mycobactin biosynthesis in Mycobacterium tuberculosis facilitates iron
      acquisition, which is required for growth and virulence. The mycobactin
      biosynthesis inhibitor salicyl-AMS [5'-O-(N-salicylsulfamoyl)adenosine] inhibits
      M. tuberculosis growth in vitro under iron-limited conditions. Here, we conducted
      a single-dose pharmacokinetic study and a monotherapy study of salicyl-AMS with
      mice. Intraperitoneal injection yielded much better pharmacokinetic parameter
      values than oral administration did. Monotherapy of salicyl-AMS at 5.6 or 16.7
      mg/kg significantly inhibited M. tuberculosis growth in the mouse lung, providing
      the first in vivo proof of concept for this novel antibacterial strategy. 

PMID- 23856771
TI  - Echocardiogram study to evaluate the effect of the novel hepatitis C virus NS5A
      inhibitor GSK2336805 on cardiac contractility in healthy subjects.
AB  - GSK2336805 is a hepatitis C virus NS5A inhibitor in clinical development for the
      treatment of chronic hepatitis C virus infection. This was a single-center,
      randomized, double-blind, placebo-controlled, two-period crossover study in
      healthy adults to evaluate the effects of a single 150-mg dose of GSK2336805 on
      echocardiographic measures of contractility. GSK2336805 had no effect on ejection
      fraction, and there was no significant correlation between GSK2336805 plasma
      concentration and ejection fraction. (This study has been registered at
      Clinicaltrials.gov under registration no. NCT01424540.). 

PMID- 23856772
TI  - Basis for early and preferential selection of the E138K mutation in HIV-1 reverse
      transcriptase.
AB  - E138K, a G->A mutation in HIV-1 reverse transcriptase (RT), is preferentially
      selected by etravirine (ETR) and rilpivirine over other substitutions at position
      E138 that offer greater drug resistance. We hypothesized that there was a
      mutational bias for the E138K substitution and designed an allele-specific PCR to
      monitor the emergence of E138A/G/K/Q/R/V during ETR selection experiments. We
      also performed competition experiments using mutated viruses and quantified the
      prevalence of E138 minority species in drug-naive patients. E138K, as well as
      E138G, consistently emerged first during ETR selection experiments, followed by
      E138A and E138Q; E138R was never selected. Surprisingly, E138K was identified as
      a tiny minority in 23% of drug-naive subtype B patients, a result confirmed by
      ultradeep sequencing (UDS). This result could reflect a low fitness cost of
      E138K; however, E138K was one of the least fit substitutions at codon E138, even
      after taking into account the deoxynucleoside triphosphate pools of the cells
      used in competition experiments. Further UDS analysis revealed other minority
      species in a pattern consistent with the mutational bias of HIV RT. There was no
      evidence of APOBEC3-hypermutation in these selection experiments or in patients.
      Our results confirm the mutational bias of HIV-1 in patients and highlight the
      importance of G->A mutations in HIV-1 drug resistance evolution. 

PMID- 23856773
TI  - Improved efficacy of fosmidomycin against Plasmodium and Mycobacterium species by
      combination with the cell-penetrating peptide octaarginine.
AB  - Cellular drug delivery can improve efficacy and render intracellular pathogens
      susceptible to compounds that cannot permeate cells. The transport of
      physiologically active compounds across membranes into target cells can be
      facilitated by cell-penetrating peptides (CPPs), such as oligoarginines. Here, we
      investigated whether intracellular delivery of the drug fosmidomycin can be
      improved by combination with the CPP octaarginine. Fosmidomycin is an antibiotic
      that inhibits the second reaction in the nonmevalonate pathway of isoprenoid
      biosynthesis, an essential pathway for many obligate intracellular pathogens,
      including mycobacteria and apicomplexan parasites. We observed a strict
      correlation between octaarginine host cell permeability and its ability to
      improve the efficacy of fosmidomycin. Plasmodium berghei liver-stage parasites
      were only partially susceptible to an octaarginine-fosmidomycin complex.
      Similarly, Toxoplasma gondii was only susceptible during the brief extracellular
      stages. In marked contrast, a salt complex of octaarginine and fosmidomycin
      greatly enhanced efficacy against blood-stage Plasmodium falciparum. This complex
      and a covalently linked conjugate of octaarginine and fosmidomycin also reverted
      resistance of Mycobacteria to fosmidomycin. These findings provide chemical
      genetic evidence for vital roles of the nonmevalonate pathway of isoprenoid
      biosynthesis in a number of medically relevant pathogens. Our results warrant
      further investigation of octaarginine as a delivery vehicle and alternative
      fosmidomycin formulations for malaria and tuberculosis drug development. 

PMID- 23856774
TI  - The R enantiomer of the antitubercular drug PA-824 as a potential oral treatment
      for visceral Leishmaniasis.
AB  - The novel nitroimidazopyran agent (S)-PA-824 has potent antibacterial activity
      against Mycobacterium tuberculosis in vitro and in vivo and is currently in phase
      II clinical trials for tuberculosis (TB). In contrast to M. tuberculosis, where
      (R)-PA-824 is inactive, we report here that both enantiomers of PA-824 show
      potent parasiticidal activity against Leishmania donovani, the causative agent of
      visceral leishmaniasis (VL). In leishmania-infected macrophages, (R)-PA-824 is 6
      fold more active than (S)-PA-824. Both des-nitro analogues are inactive,
      underlining the importance of the nitro group in the mechanism of action.
      Although the in vitro and in vivo pharmacological profiles of the two enantiomers
      are similar, (R)-PA-824 is more efficacious in the murine model of VL, with >99%
      suppression of parasite burden when administered orally at 100 mg kg of body
      weight(-1), twice daily for 5 days. In M. tuberculosis, (S)-PA-824 is a prodrug
      that is activated by a deazaflavin-dependent nitroreductase (Ddn), an enzyme
      which is absent in Leishmania spp. Unlike the case with nifurtimox and
      fexinidazole, transgenic parasites overexpressing the leishmania nitroreductase
      are not hypersensitive to either (R)-PA-824 or (S)-PA-824, indicating that this
      enzyme is not the primary target of these compounds. Drug combination studies in
      vitro indicate that fexinidazole and (R)-PA-824 are additive whereas (S)-PA-824
      and (R)-PA-824 show mild antagonistic behavior. Thus, (R)-PA-824 is a promising
      candidate for late lead optimization for VL and may have potential for future use
      in combination therapy with fexinidazole, currently in phase II clinical trials
      against VL. 

PMID- 23856775
TI  - Differential adaptive responses of Staphylococcus aureus to in vitro selection
      with different antimicrobial peptides.
AB  - We subjected Staphylococcus aureus ATCC 29213 to serial passage in the presence
      of subinhibitory concentrations of magainin 2 and gramicidin D for several
      hundred generations. We obtained S. aureus strains with induced resistance to
      magainin 2 (strain 55MG) and gramicidin D (strain 55GR) that showed different
      phenotypic changes in membrane properties. Both exhibited a change in membrane
      phospholipid content and an increase in membrane rigidity, while an alteration in
      net charge compared to that of the control occurred only in the case of 55MG. 

PMID- 23856776
TI  - Effect of intracellular expression of antimicrobial peptide LL-37 on growth of
      escherichia coli strain TOP10 under aerobic and anaerobic conditions.
AB  - Antimicrobial peptides (AMPs) can cause lysis of target bacteria by directly
      inserting themselves into the lipid bilayer. This killing mechanism confounds the
      identification of the intracellular targets of AMPs. To circumvent this, we used
      a shuttle vector containing the inducible expression of a human cathelicidin
      related AMP, LL-37, to examine its effect on Escherichia coli TOP10 under aerobic
      and anaerobic growth conditions. Induction of LL-37 caused growth inhibition and
      alteration in cell morphology to a filamentous phenotype. Further examination of
      the E. coli cell division protein FtsZ revealed that LL-37 did not interact with
      FtsZ. Moreover, intracellular expression of LL-37 results in the enhanced
      production of reactive oxygen species (ROS), causing lethal membrane
      depolarization under aerobic conditions. Additionally, the membrane permeability
      was increased after intracellular expression of LL37 under both aerobic and
      anaerobic conditions. Transcriptomic analysis revealed that intracellular LL-37
      mainly affected the expression of genes related to energy production and
      carbohydrate metabolism. More specifically, genes related to oxidative
      phosphorylation under both aerobic and anaerobic growth conditions were affected.
      Collectively, our current study demonstrates that intracellular expression of LL
      37 in E. coli can inhibit growth under aerobic and anaerobic conditions. While we
      confirmed that the generation of ROS is a bactericidal mechanism for LL-37 under
      aerobic growth conditions, we also found that the intracellular accumulation of
      cationic LL-37 influences the redox and ion status of the cells under both growth
      conditions. These data suggest that there is a new AMP-mediated bacterial killing
      mechanism that targets energy metabolism. 

PMID- 23856777
TI  - Characterization of ribosomal binding and antibacterial activities using two
      orthogonal high-throughput screens.
AB  - We report here the affinity and antibacterial activity of a structurally similar
      class of neomycin dimers. The affinity of the dimer library for rRNA was
      established by using a screen that measures the displacement of fluorescein
      neomycin (F-neo) probe from RNA. A rapid growth inhibition assay using a single
      drug concentration was used to examine the antibacterial activity. The structure
      activity relationship data were then rapidly analyzed using a two-dimensional
      ribosomal binding-bacterial inhibition plot analysis. 

PMID- 23856778
TI  - A peptide inhibitor of cytomegalovirus infection from human hemofiltrate.
AB  - Naturally occurring substances with antimicrobial activity can serve as a
      starting point for the rational design of new drugs to treat infectious diseases.
      Here, we screened a library of peptides derived from human hemofiltrate for
      inhibitory effects on human cytomegalovirus (CMV) infection. We isolated a
      previously unknown derivative of the neutrophil-activating peptide 2, which we
      termed CYVIP, for CMV-inhibiting peptide. The peptide blocked infection with
      human and mouse CMV as well as with herpes simplex virus type 1 in different cell
      types. We found that CYVIP interferes with virus attachment to the cell surface,
      and structure-activity relationship studies revealed that positively charged
      lysine and arginine residues of CYVIP are essential for its inhibitory activity.
      The N-terminal 29 amino acids of the peptide were sufficient for inhibition, and
      substitution with an acidic residue further improved its activity. The target
      structure of CYVIP on the cell surface seems to be the sulfate residues of
      heparan sulfate proteoglycans, which are known to serve as herpesvirus attachment
      receptors. Our data suggest that O-sulfation of heparan sulfate is required for
      binding of CYVIP, and furthermore, that the initial interaction of CMV particles
      with cells takes place preferentially via 6-O-linked sulfate groups. These
      findings about CYVIP's mode of action lay the basis for further development of
      antivirals interfering with attachment of CMV to cells, a crucial step of the
      infection cycle. 

PMID- 23856779
TI  - Antiviral effect, safety, and pharmacokinetics of five-day oral administration of
      Deleobuvir (BI 207127), an investigational hepatitis C virus RNA polymerase
      inhibitor, in patients with chronic hepatitis C.
AB  - Deleobuvir (BI 207127) is an investigational oral nonnucleoside inhibitor of
      hepatitis C virus (HCV) NS5B RNA polymerase. Antiviral activity, virology,
      pharmacokinetics, and safety were assessed in HCV genotype 1-infected patients
      receiving 5 days' deleobuvir monotherapy. In this double-blind phase 1b study,
      treatment-naive (TN; n = 15) and treatment-experienced (TE; n = 45) patients
      without cirrhosis received placebo or deleobuvir at 100, 200, 400, 800, or 1,200
      mg every 8 h (q8h) for 5 days. Patients with cirrhosis (n = 13) received
      deleobuvir at 400 or 600 mg q8h for 5 days. Virologic analyses included NS5B
      genotyping and phenotyping of individual isolates. At day 5, patients without
      cirrhosis had dose-dependent median HCV RNA reductions of up to 3.8 log10 (with
      no placebo response); patients with cirrhosis had median HCV RNA reductions of
      approximately 3.0 log10. Three patients discontinued due to adverse events (AEs).
      The most common AEs were gastrointestinal, nervous system, and skin/cutaneous
      tissue disorders. Plasma exposure of deleobuvir was supraproportional at doses >=
      400 mg q8h and approximately 2-fold higher in patients with cirrhosis than in
      patients without cirrhosis. No virologic breakthrough was observed. NS5B
      substitutions associated with deleobuvir resistance in vitro were detected in
      9/59 patients; seven encoded P495 substitutions, including P495L, which conferred
      120- to 310-fold-decreased sensitivity to deleobuvir. P495 variants did not
      persist in follow-up without selective drug pressure. Deleobuvir monotherapy was
      generally well tolerated and demonstrated dose-dependent antiviral activity
      against HCV genotype 1 over 5 days. 

PMID- 23856780
TI  - Chimeric Cyanovirin-MPER recombinantly engineered proteins cause cell-free
      virolysis of HIV-1.
AB  - Human immunodeficiency virus (HIV) is the primary etiologic agent responsible for
      the AIDS pandemic. In this work, we used a chimeric recombinant protein strategy
      to test the possibility of irreversibly destroying the HIV-1 virion using an
      agent that simultaneously binds the Env protein and viral membrane. We
      constructed a fusion of the lectin cyanovirin-N (CVN) and the gp41 membrane
      proximal external region (MPER) peptide with a variable-length (Gly4Ser)x linker
      (where x is 4 or 8) between the C terminus of the former and N terminus of the
      latter. The His-tagged recombinant proteins, expressed in BL21(DE3)pLysS cells
      and purified by immobilized metal affinity chromatography followed by gel
      filtration, were found to display a nanomolar efficacy in blocking BaL
      pseudotyped HIV-1 infection of HOS.T4.R5 cells. This antiviral activity was HIV-1
      specific, since it did not inhibit cell infection by vesicular stomatitis virus
      (VSV) or amphotropic-murine leukemia virus. Importantly, the chimeric proteins
      were found to release intraviral p24 protein from both BaL-pseudotyped HIV-1 and
      fully infectious BaL HIV-1 in a dose-dependent manner in the absence of host
      cells. The addition of either MPER or CVN was found to outcompete this virolytic
      effect, indicating that both components of the chimera are required for
      virolysis. The finding that engaging the Env protein spike and membrane using a
      chimeric ligand can destabilize the virus and lead to inactivation opens up a
      means to investigate virus particle metastability and to evaluate this approach
      for inactivation at the earliest stages of exposure to virus and before host cell
      encounter. 

PMID- 23856781
TI  - Association of fluoroquinolone resistance, virulence genes, and IncF plasmids
      with extended-spectrum-beta-lactamase-producing Escherichia coli sequence type
      131 (ST131) and ST405 clonal groups.
AB  - The global increase of extended-spectrum-beta-lactamase (ESBL)-producing
      Escherichia coli is associated with the specific clonal group sequence type 131
      (ST131). In order to understand the successful spread of ESBL-producing E. coli
      clonal groups, we characterized fluoroquinolone resistance determinants,
      virulence genotypes, and plasmid replicons of ST131 and another global clonal
      group, ST405. We investigated 41 ST131-O25b, 26 ST131-O16, 41 ST405, and 41 other
      ST (OST) ESBL-producing isolates, which were collected at seven acute care
      hospitals in Japan. The detection of ESBL types, fluoroquinolone resistance
      associated mutations (including quinolone resistance-determining regions
      [QRDRs]), virulence genotypes, plasmid replicon types, and IncF replicon sequence
      types was performed using PCR and sequencing. blaCTX-M, specifically blaCTX-M-14,
      was the most common ESBL gene type among the four groups. Ciprofloxacin
      resistance was found in 90% of ST131-O25b, 19% of ST131-O16, 100% of ST405, and
      54% of OST isolates. Multidrug resistance was more common in the ST405 group than
      in the ST131-O25 group (56% versus 32%; P = 0.045). All ST131-O25b isolates
      except one had four characteristic mutations in QRDRs, but most of the isolates
      from the other three groups had three mutations in common. The ST131-O25b and
      ST405 groups had larger numbers of virulence genes than the OST group. All of the
      ST131-O25b and ST405 isolates and most of the ST131-O16 and OST isolates carried
      IncF replicons. The most prevalent IncF replicon sequence types differed between
      the four clonal groups. Both the ST131-O25b and ST405 clonal groups had a
      fluoroquinolone resistance mechanism in QRDRs, multidrug resistance, high
      virulence, and IncF plasmids, suggesting the potential for further global
      expansion and a need for measures against these clonal groups. 

PMID- 23856782
TI  - Antiviral efficacy of favipiravir against two prominent etiological agents of
      hantavirus pulmonary syndrome.
AB  - Hantavirus pulmonary syndrome (HPS) is caused by infection with several
      Sigmodontinae- and Neotominae-borne hantaviruses and has a case fatality rate of
      30 to 50%. Humans often become infected by inhalation of materials contaminated
      with virus-laden rodent urine or saliva, although human-to-human transmission has
      also been documented for Andes virus (ANDV). The ability to transmit via
      aerosolization, coupled with the high mortality rates and lack of therapeutic
      options, makes the development of medical countermeasures against HPS imperative.
      In the present study, we evaluated the efficacy of the broad-spectrum antiviral
      agent favipiravir (T-705) against Sin Nombre virus (SNV) and ANDV, the
      predominant causes of HPS in North and South America, respectively. In vitro, T
      705 potently inhibited SNV and ANDV, as evidenced by decreased detection of viral
      RNA and reduced infectious titers. For both viruses, the 90% effective
      concentration was estimated at <=5 MUg/ml (<=31.8 MUM). In the lethal ANDV
      hamster model, daily administration of oral T-705 at 50 or 100 mg/kg of body
      weight diminished the detection of viral RNA and antigen in tissue specimens and
      significantly improved survival rates. Oral T-705 therapy remained protective
      against HPS when treatment was initiated prior to the onset of viremia. No
      disease model for SNV exists; however, using a hamster-adapted SNV, we found that
      daily administration of oral T-705 significantly reduced the detection of SNV RNA
      and antigen in tissue specimens, suggesting that the compound would also be
      effective against HPS in North America. Combined, these results suggest that T
      705 treatment is beneficial for postexposure prophylaxis against HPS-causing
      viruses and should be considered for probable exposures. 

PMID- 23856783
TI  - DNA microarray for genotyping antibiotic resistance determinants in Acinetobacter
      baumannii clinical isolates.
AB  - In recent decades, Acinetobacter baumannii has emerged as an organism of great
      concern due to its ability to accumulate antibiotic resistance. In order to
      improve the diagnosis of resistance determinants in A. baumannii in terms of lead
      time and accuracy, we developed a microarray that can be used to detect 91 target
      sequences associated with antibiotic resistance within 4 h from bacterial culture
      to result. The array was validated with 60 multidrug-resistant strains of A.
      baumannii in a blinded, prospective study. The results were compared to phenotype
      results determined by the automated susceptibility testing system VITEK2.
      Antibiotics considered were piperacillin-tazobactam, ceftazidime, imipenem,
      meropenem, trimethoprim-sulfamethoxazole, amikacin, gentamicin, tobramycin,
      ciprofloxacin, and tigecycline. The average positive predictive value, negative
      predictive value, sensitivity, and specificity were 98, 98, 99, and 94%,
      respectively. For carbapenemase genes, the array results were compared to
      singleplex PCR results provided by the German National Reference Center for Gram
      Negative Pathogens, and results were in complete concordance. The presented array
      is able to detect all relevant resistance determinants of A. baumannii in
      parallel. The short handling time of 4 h from culture to result helps to provide
      fast results in order to initiate adequate anti-infective therapy for critically
      ill patients. Another application would be data acquisition for epidemiologic
      surveillance. 

PMID- 23856784
TI  - Characterization of binding of raltegravir to plasma proteins.
AB  - The objective of this study was to characterize raltegravir (RAL) binding to
      albumin and alpha-1-acid glycoprotein (AAG). Unbound and bound RAL were separated
      by ultrafiltration. The association constant (Ka) was estimated by a graphical
      method. In HIV-infected patients, the average plasma protein binding is 76%. RAL
      did not bind to AAG but bound to nonsaturable, low-affinity albumin sites with an
      n (number of sites) . Ka product of 9.8 * 10(2) liters/mol. A pH increase of 0.2
      U led to a 2% increase in the bound fraction. 

PMID- 23856785
TI  - Unusually severe cases of Kingella kingae osteoarticular infections in children.
AB  - BACKGROUNDS: With the development of molecular biology and specific polymerase
      chain reaction, Kingella kingae has become the primary diagnosis of
      osteoarticular infections in young children. Clinical features of these
      osteoarticular infections are typically mild, and outcome is almost always
      favorable. We report a series of unusually severe cases of K. kingae
      osteoarticular infections. METHODS: All patients with severe osteoarticular
      infections at presentation were reviewed retrospectively in 2 European pediatric
      centers. K. kingae was identified using real-time polymerase chain reaction in
      blood, fluid joint or osseous samples. Clinical, laboratory tests and
      radiographic data during hospitalization and follow-up were analyzed. RESULTS:
      Ten children (mean age 21 +/- 12 months) with severe osteoarticular infections
      caused by K. kingae were identified between 2008 and 2011. Diagnostic delay
      averaged 13.2 +/- 8 days. Only 1 patient was febrile at admission, and 50%
      children had normal C-reactive protein values (<=10 mg/dL) at presentation.
      Surgical treatment was performed in all cases. Intravenous antibiotic therapy by
      cephalosporins for an average of 8 +/- 6 days was followed by oral treatment for
      27 +/- 6 days. Mean follow-up was 24.8 +/- 9 months, and satisfactory outcomes
      were reported in all cases. Two patients (20%) developed a central epiphysiodesis
      of the proximal humerus during follow-up, but without significant clinical
      consequence for the moment. CONCLUSIONS: Because of their mild clinical features
      at onset, diagnosis of K. kingae osteoarticular infections can be delayed. Care
      should be taken for early detection and treatment of these infections because
      bony lytic lesions and potentially definitive growth cartilage damage can occur.

PMID- 23856786
TI  - Effectiveness of pneumococcal conjugate vaccine in infants by maternal influenza
      vaccination status.
AB  - BACKGROUND: Influenza virus infection can predispose patients to secondary
      pneumococcal infections. Children are at greatest risk for pneumococcal infection
      in the first year of life and are not considered fully protected by pneumococcal
      conjugate vaccine (PCV) until their third dose at 6 months of age. Infants less
      than 6 months cannot receive influenza vaccination, though maternal influenza
      vaccination can protect infants. METHODS: We conducted a retrospective cohort
      study of 9807 mother-infant pairs enrolled in a managed care organization for
      infants born June 1, 2002, to December 31, 2009. Exposure was assessed for
      receipt of infant PCV only and the combination of PCV and maternal influenza
      vaccine (trivalent inactivated vaccine). Outcomes of interest were acute otitis
      media and medically attended acute respiratory infection in the first year of
      life. We estimated the adjusted incidence of illness, incidence rate ratios and
      vaccine effectiveness using the ratio of incidence rate ratios between the
      periods of noncirculating influenza and that of at least local influenza
      circulation. RESULTS: For medically attended acute respiratory infection, vaccine
      effectiveness for the combination of trivalent inactivated vaccine and PCV was
      39.6% (95% confidence interval [CI]: 31.6%-46.7%) and for PCV only was 29.8% (95%
      CI: 11.4%-44.3%). For acute otitis media, vaccine effectiveness for the
      combination of trivalent inactivated vaccine and PCV was 47.9% (95% CI: 42%
      53.3%) and for PCV only was 37.6% (95% CI: 23.1%-49.4%). CONCLUSION: In infants,
      the combination of maternal influenza vaccine and infant pneumococcal conjugate
      vaccination confers greater protection from acute otitis media infections and
      medically attended acute respiratory infections than does PCV alone.

PMID- 23856787
TI  - Speckle-based configuration for simultaneous in vitro inspection of mechanical
      contractions of cardiac myocyte cells.
AB  - An optical lensless configuration for a remote noncontact measuring of mechanical
      contractions of a vast number of cardiac myocytes is proposed. All the myocytes
      were taken from rats, and the measurements were done in an in vitro mode. The
      optical method is based on temporal analysis of secondary reflected speckle
      patterns generated in lensless microscope configuration. The processing involves
      analyzing the movement and the change in the statistics of the secondary speckle
      patterns that are created on top of the cell culture when it is illuminated by a
      spot of laser beam. The main advantage of the proposed system is the ability to
      measure many cells simultaneously (~1000 cells) and to extract the statistical
      data of their movement at once. The presented experimental results also include
      investigation of the effect of isoproteranol on cell contraction process.

PMID- 23856788
TI  - The effect of increased private sector involvement in solid waste collection in
      five cities in Ghana.
AB  - Private sector involvement in solid waste management in developing countries has
      increased, but the effect is not always clear. This study assesses how it has
      been organized in five cities in Ghana, what has been its effect and what lessons
      for private sector development in developing countries can be drawn. Data were
      collected from 25 private companies and a sample of 1200 households. More than
      60% of solid waste in Ghanaian cities is now collected by private enterprises.
      Sometimes, and increasingly, competitive bidding takes place, although sometimes
      no bidding is organized leading to rendering of this service and no contract
      being signed. Local governments and local solid waste companies have not changed
      to more customer-oriented delivery because of the slow pace of charging users and
      the resulting low rate of cost recovery. The participation of the population has
      been limited, which contributes to low cost recovery. However, a gradual better
      functioning of the system put in place is shown. We observed an increasing use of
      competitive bidding, signing of contracts and city-wide user charging. 

PMID- 23856789
TI  - Hollow-fiber membrane bioreactor for the treatment of high-strength landfill
      leachate.
AB  - Performance assessment of membrane bioreactor (MBR) technology for the
      treatability of high-strength landfill leachate is relatively limited or lacking.
      This study examines the feasibility of treating high-strength landfill leachate
      using a hollow-fiber MBR. For this purpose, a laboratory-scale MBR was
      constructed and operated to treat leachate with a chemical oxygen demand (COD) of
      9000-11,000 mg/l, a 5-day biochemical oxygen demand (BOD5) of 4000-6,000 mg/l,
      volatile suspended solids (VSS) of 300-500 mg/l, total nitrogen (TN) of 2000-6000
      mg/l, and an ammonia-nitrogen (NH3-N) of 1800-4000 mg/l. VSS was used with the
      BOD and COD data to simulate the biological activity in the activated sludge.
      Removal efficiencies > 95-99% for BOD5, VSS, TN and NH3-N were attained. The
      coupled experimental and simulation results contribute in filling a gap in
      managing high-strength landfill leachate and providing guidelines for
      corresponding MBR application. 

PMID- 23856790
TI  - Multi-stakeholder decision analysis and comparative risk assessment for reuse
      recycle oriented e-waste management strategies: a game theoretic approach.
AB  - This article deals with assessment of the potential health risk posed by
      carcinogenic and non-carcinogenic substances, namely lead (Pb), cadmium (Cd),
      copper, chromium (CrVI), zinc, nickel and mercury, present in e-waste. A multi
      objective, multi-stakeholder approach based on strategic game theory model has
      been developed considering cost, as well as human health risk. The trade-off due
      to cost difference between a hazardous substances-free (HSF) and a hazardous
      substance (HS)-containing desktop computer, and the risk posed by them at the
      time of disposal, has been analyzed. The cancer risk due to dust inhalation for
      workers at a recycling site in Bangalore for Pb, Cr(VI) and Cd was found to be 4,
      33 and 101 in 1 million respectively. Pb and Cr(VI) result in a very high risk
      owing to dust ingestion at slums near the recycling site--175 and 81 in 1 million
      for children, and 24 and 11 in 1 million for adults respectively. The
      concentration of Pb at a battery workshop in Mayapuri, Delhi (hazard quotient =
      3.178) was found to pose adverse health hazards. The government may impose an
      appropriate penalty on the land disposal of computer waste and/or may give an
      incentive to manufacturer for producing HSF computers through, for example,
      relaxing taxes, but there should be no such incentive for manufacturing HS
      containing computers.

PMID- 23856791
TI  - Alexander and the Guidelines: the importance of strategy and the guidelines for
      the diagnosis and medicamentous treatment of rheumatoid arthritis.

PMID- 23856792
TI  - Antiphospholipid syndrome.

PMID- 23856793
TI  - Guidelines for the diagnosis of rheumatoid arthritis.

PMID- 23856794
TI  - Guidelines for the drug treatment of rheumatoid arthritis.

PMID- 23856795
TI  - Guidelines for the treatment of antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is a systemic autoimmune disease
      characterized by arterial and venous thrombosis, gestational morbidity and
      presence of elevated and persistently positive serum titers of antiphospholipid
      antibodies. The treatment of APS is still controversial, because any therapeutic
      decision potentially faces the risk of an insufficient or excessive
      antithrombotic coverage associated with anticoagulation and its major adverse
      effects. This guideline was elaborated from nine relevant clinical questions
      related to the treatment of APS by the Committee of Vasculopathies of the
      Brazilian Society of Rheumatology. Thus, this study aimed at establishing a
      guideline that included the most relevant and controversial questions in APS
      treatment, based on the best scientific evidence available. The questions were
      structured by use of the PICO (patient, intervention or indicator, comparison and
      outcome) process, enabling the generation of search strategies for evidence in
      the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo,
      Cochrane Library, Premedline via OVID). A manual search for evidence and theses
      was also conducted (BDTD and IBICT). The evidence retrieved was selected based on
      critical assessment by using discriminatory instruments (scores) according to the
      category of the therapeutic question (JADAD scale for randomized clinical trials
      and Newcastle-Ottawa scale for non-randomized studies). After defining the
      potential studies to support the recommendations, they were selected according to
      level of evidence and grade of recommendation, according to the Oxford
      classification. 

PMID- 23856796
TI  - Resistance training versus weight-bearing aquatic exercise: a cross-sectional
      analysis of bone mineral density in postmenopausal women.
AB  - INTRODUCTION: Many studies have shown that resistance training has a positive
      effect on bone mineral density (BMD). However, few studies have compared the BMD
      of individuals undergoing resistance training and those training aquatic weight
      bearing exercises. OBJECTIVE: To compare, in a cross-sectional study, the BMD of
      postmenopausal women undergoing resistance training and postmenopausal women
      training aquatic weight-bearing exercises. METHODS: The sample comprised 63 women
      divided into the following three groups: resistance training (STRENGTH: n = 15;
      51.4 +/- 2.7 years); aquatic weight-bearing exercises (WA-TER: n = 22; 54.5 +/-
      3.3 years); and non-trained controls ( CONTROL: n = 26; 52.0 +/- 3.3 years). All
      volunteers were on hormone replacement therapy for at least one year. The
      STRENGTH and WATER groups were training for at least one year prior to study
      beginning (mean years of training - STRENGTH: 4.5 +/- 2.0; WATER: 4.2 +/- 2.2).
      RESULTS: The STRENGTH group had higher BMD of total body, femoral neck, lumbar
      spine L2-L4 as compared with the CONTROL group (all P < 0.05). The WATER group
      had higher BMD of total body, total hip, lumbar spine L2-L4 as compared with the
      CONTROL group (all P < 0.05). However, no difference was observed between the
      STRENGTH and WATER groups regarding the sites assessed. CONCLUSIONS: Those
      findings suggest that not only the resistance training, but also aquatic weight
      bearing exercises might be a non-pharmacological strategy to prevent BMD loss in
      postmenopausal women.

PMID- 23856797
TI  - Lack of association between interleukin-18 polymorphisms and rheumatoid
      arthritis.
AB  - OBJECTIVE: To assess the association of the polymorphisms of the interleukin-18
      (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for
      cardiovascular diseases (CVD). METHODS: This sample comprised 97 patients with RA
      and 151 healthy controls. In the patients, risk factors for CVD were analyzed,
      such as cholesterol levels, arterial hypertension, smoking habit, C-reactive
      protein (CRP) level, and rheumatoid factor. DNA was extracted and the single
      nucleotide polymorphisms (SNP) at the -607C/A and -137G/C positions of the IL-18
      gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was
      calculated and the odds ratio (OR) test performed, considering a 95% CI and P <
      0.05. RESULTS: The frequencies of the -607A allele in patients with RA and in
      controls were 0,443 and 0.424, respectively, and of the -137C allele, 0.304 and
      0.291, respectively. The genotype frequencies were in HWE, except for controls in
      the -137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene
      was found with neither RA nor risk factors for CVD, including cholesterol level
      and CRP (P > 0.05). In addition, more smokers were found among patients with RA
      as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were
      slightly higher in patients who smoked than in patients who did not (OR = 2.673;
      P = 0.061). CONCLUSIONS: In this sample of patients with RA in the South of
      Brazil, association of the polymorphisms of the IL-18 gene was observed with
      neither RA nor risk factors for CVD.

PMID- 23856798
TI  - What a rheumatologist needs to know about yellow fever vaccine.
AB  - Patients with rheumatic diseases are more susceptible to infection, due to the
      underlying disease itself or to its treatment. The rheumatologist should prevent
      infections in those patients, vaccination being one preventive measure to be
      adopted. Yellow fever is one of such infectious diseases that can be avoided.The
      yellow fever vaccine is safe and effective for the general population, but, being
      an attenuated live virus vaccine, it should be avoided whenever possible in
      rheumatic patients on immunosuppressive drugs. Considering that yellow fever is
      endemic in a large area of Brazil, and that vaccination against that disease is
      indicated for those living in such area or travelling there, rheumatologists need
      to know that disease, as well as the indications for the yellow fever vaccine and
      contraindications to it. Our paper was aimed at highlighting the major aspects
      rheumatologists need to know about the yellow fever vaccine to decide about its
      indication or contraindication in specific situations. 

PMID- 23856799
TI  - Update on the treatment of calcinosis in dermatomyositis.
AB  - Calcinosis is a connective tissue disorder classified into the following four
      types: metastatic; idiopathic; iatrogenic and dystrophic. Dystrophic calcinosis
      can occur, for example, in dermatomyositis, mainly in juvenile dermatomyositis,
      and is characterized by an abnormal deposition of calcium salts in affected skin,
      subcutaneous tissues, and muscles or tendons, with normal serum levels of calcium
      and phosphate. The treatment of calcinosis in dermatomyositis remains a
      challenge, with few descriptions in the literature of low scientific evidence. So
      far, no therapy has proved to be highly effective in the combat and resolution of
      that comorbidity. The present study discusses the concept of calcinosis,
      particularly in dermatomyositis, as well as its treatment described in the
      literature. 

PMID- 23856800
TI  - Chondrolysis of the hip in an adolescent: clinical and radiological outcomes.
AB  - Idiopathic chondrolysis of the hip is a rare condition of unknown etiology
      characterized by progressive destruction of the hyaline cartilage that covers the
      femoral head and acetabulum. Idiopathic chondrolysis of the hip has an insidious
      beginning and affects more often female adolescents. Patients report severe hip
      pain, mobility limitation, and even claudication. This study aimed at reporting
      one case of that rare disease: an 11-year-old female adolescent with
      chondrolysis, followed up for three years. Inflammatory activity tests were
      normal. Imaging tests (radiography, ultrasonography and magnetic resonance) were
      essential for the diagnosis. The treatment was based on pain control and
      preservation of the joint mobility, and included low-impact physical activity,
      non-steroidal anti-inflammatory drugs, and disease-modifying antirheumatic drugs,
      with good response after 12 months of treatment. Surgery was not necessary. 

PMID- 23856801
TI  - Mesenteric vasculitis in a juvenile systemic lupus erythematosus patient.
AB  - Lupus mesenteric vasculitis (LMV) is a rare cause of acute abdominal pain. Few
      cases of LMV have been reported in adults, children and adolescents. However, to
      our knowledge, the prevalence of that severe vasculitis in a pediatric population
      with lupus is yet to be studied. This study reviewed data from 28 consecutive
      years and included 5,508 patients being followed up at the hospital of the
      Faculdade de Medicina of the Univesidade de Sao Paulo (FMUSP). We identified 279
      (5.1%) patients meeting the American College of Rheumatology classification
      criteria for the diagnosis of systemic lupus erythematosus (SLE), one of whom
      (0.4%) had LMV. That male patient was diagnosed with SLE at the age of 11 years.
      At the age of 13 years, he was hospitalized with diffuse and acute abdominal
      pain, nausea, bilious vomiting, abdominal distension, rebound tenderness, and
      abdominal muscle guarding. The patient underwent laparotomy immediately, and
      segmentary intestinal ischemia with intestinal wall edema and adhesions were
      identified. Partial small bowel resection with lysis of the adhesions was
      performed, as were pulses of intravenous methylprednisolone. The histopathologic
      analysis evidenced mesenteric arteritis. After 13 days, the diffuse and intense
      abdominal pain recurred, and the patient underwent a new laparotomy, during which
      adhesive small bowel obstruction with intestinal gangrene was identified. New
      intestinal resection was performed, and the patient received pulses of
      intravenous methylprednisolone and infusion of immunoglobulin. Thus, LMV is a
      rare and severe abdominal manifestation of the pediatric population with lupus,
      and can be the only manifestation of disease activity. In addition, this study
      stresses the importance of the early diagnosis and immediate treatment.

PMID- 23856803
TI  - Reconstruction of post-traumatic losses of substance of the scalp: our
      experience.
AB  - AIM: The reconstruction of post-traumatic losses of substance of the scalp is
      very difficult due to the unique characteristics of the scalp. The purpose of
      this paper is to evaluate the results obtained with several techniques in order
      to identify the most appropriate. METHODS: We treated 19 patients, 11 men and 8
      women aged between 19 and 81 years, with post-traumatic loss of substance of the
      scalp from January 2006 to June 2011. The chosen treatments were the direct
      closure and the use of local flaps, the latter combined or not with the graft of
      the donor area and the post-operative correction of alopecic area with tissue
      expansion. RESULTS: None of the patients developed severe complications and all
      flaps were viable. The aesthetic results were variable, between good and
      satisfactory according to the technique used. CONCLUSION: The local flaps
      represent a good choice for the treatment of post-traumatic losses of substance
      of the scalp, restricting the use of direct suture and the use of skin grafting
      only in selected cases. Tissue expansion is a good choice for the revision of
      alopecic and cicatricial areas.

PMID- 23856802
TI  - Patient-centered decision making in the treatment of chronic rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: To explore possible factors that might impact a patient's
      choice to pursue endoscopic sinus surgery (ESS) or continue with medical
      management for treatment of refractory chronic rhinosinusitis (CRS). STUDY
      DESIGN: Cross-sectional evaluation of a multicenter prospective cohort. METHODS:
      Two hundred forty-two subjects with CRS were prospectively enrolled within four
      academic tertiary care centers across North America with ongoing symptoms despite
      prior medical treatment. Subjects either self-selected continued medical
      management (n = 62) or ESS (n = 180) for treatment of sinonasal symptoms.
      Differences in demographics, comorbid conditions, and clinical measures of
      disease severity between subject groups were compared. Validated metrics of
      social support, personality, risk aversion, and physician-patient relationships
      were compared using bivariate analyses, predicted probabilities, and receiver
      operating characteristic curves at the 0.05 alpha level. RESULTS: No significant
      differences were found between treatment groups for any demographic
      characteristic, clinical cofactor, or measure of social support, personality, or
      the physician-patient relationship. Subjects electing to pursue sinus surgery did
      report significantly worse average quality-of-life (QOL) scores on the 22-item
      Sinonasal Outcome Test (SNOT-22; P < .001) compared to those electing continued
      medical therapy (54.6 +/- 18.9 vs. 39.4 +/- 17.7), regardless of surgical history
      or polyp status. SNOT-22 score significantly predicted treatment selection (odds
      ratio, 1.046; 95% confidence interval, 1.028-1.065; P < .001) and was found to
      accurately discriminate between subjects choosing endoscopic sinus surgery and
      those electing medical management 72% of the time. CONCLUSIONS: Worse patient
      reported disease severity, as measured by the SNOT-22, was significantly
      associated with the treatment choice for CRS. Strong consideration should be
      given for incorporating CRS-specific QOL measures into routine clinical practice.
      LEVEL OF EVIDENCE: 2b.

PMID- 23856804
TI  - Supraorbital nerve entrapment neuropathy in Hansen's disease.

PMID- 23856805
TI  - Predictive factors of diagnostic accuracy of CT-guided transthoracic fine-needle
      aspiration for solid noncalcified, subsolid and mixed pulmonary nodules.
AB  - PURPOSE: The aim of this study was to analyse factors predicting the diagnostic
      accuracy of computed tomography (CT)-guided transthoracic fine-needle aspiration
      (TTFNA) for solid noncalcified, subsolid and mixed pulmonary nodules, with
      particular attention to those responsible for false negative results with a view
      to suggesting a method for their correction. MATERIALS AND METHODS: From January
      2007 to March 2010, we retrospectively reviewed the CT images of 198 patients of
      both sexes (124 males and 74 females; mean age, 70 years; range age, 44-90) used
      for the guidance of TTFNA of pulmonary nodules. Aspects considered were: lesion
      size and density, distance from the pleura, and lesion site. Multiplanar
      reformatted images (MPR) were retrospectively obtained in the sagittal and axial
      oblique planes relative to needle orientation. RESULTS: The overall diagnostic
      accuracy of TTFNA CT-guided biopsy was 86% for nodules between 0.7 and 3 cm,
      83.3% for those between 0.7 and 1.5 cm, and 92% for those between 2 and 3 cm.
      Accuracy was 95.1% for solid pulmonary nodules, 84.6% for mixed nodules, and
      66.6% for subsolid nodules. The diagnostic accuracy of CT-guided TTFNA in
      relation to the distance between the nodule and the pleural plane was 95.6% for
      lesions adhering to the pleura and 83.5% for central ones. The diagnostic
      accuracy was 84.2% for the pulmonary upper lobe nodules, 85.3% for the lower lobe
      and 90.9% for those in the lingula and middle lobe. In 75% of false negative and
      inadequate/insufficient cases the needle was found to lie outside the lesion,
      after reconstruction of the needle path by MPR. CONCLUSIONS: The positive
      predictive factors of CT-guided TTFNA are related to the nodule size, density and
      distance from the pleural plane. The most common negative predictive factor of CT
      guided TTFNA is the wrong position of the needle tip, as observed in the sagittal
      and axial oblique sections of the MPR reconstructions. The diagnostic accuracy of
      CT-guided TTFNA can therefore be improved by using the MPR technique to plan the
      needle path during the FNA procedure.

PMID- 23856806
TI  - Subsegmental pulmonary embolism: is the emperor still naked?

PMID- 23856807
TI  - Accumulation of trace metals in two commercially important shrimp species from
      Camamu Bay, Northeastern Brazil.
AB  - Camamu Bay is the second largest estuary in Bahia state, northeastern Brazil,
      being recognized by its high diversity and economical relevance for fisheries and
      tourism. To evaluate the impacts of environmental disturbances in Camamu Bay,
      trace metals (Cr, Mn, Fe, Co, Ni, Cu, and Pb) were quantified in two widespread
      and commercially exploited shrimp species (Farfantepenaeus paulensis and
      Xiphopenaeus kroyeri). High concentrations of all metals but Pb were observed in
      both species by ICPOES. The concentration values for Cr, Co, and Mn were
      invariably higher than the accepted limits for human consumption in Brazil. Inter
      and intraspecific variation in metal levels might be related to biological
      particularities and body size. The accentuated contamination by trace metals in
      both species validated them as efficient bioindicators of environmental quality.
      Thus, effective planning, monitoring and regulatory policies should be adopted to
      inspect and remediate the metal contamination in natural resources from Camamu
      Bay.

PMID- 23856808
TI  - Traumatic dental injuries in primary teeth: severity and related factors observed
      at a specialist treatment centre in Brazil.
AB  - AIM: This retrospective study aimed to analyse demographic data and the severity
      of traumatic dental injuries (TDIs) to the primary dentition based on children's
      dental records at a university clinic. STUDY DESIGN: A cross-sectional
      retrospective study. METHODS: The records of all patients were analysed according
      to gender, age, aetiology, teeth involved, number of affected teeth, place of
      occurrence, witness to the trauma, time elapsed between trauma occurrence and
      care-seeking, type of trauma and severity of injury. RESULTS: A total of 576
      children aged 8-89 months suffered injuries to 1,043 teeth. Severe injuries were
      the most prevalent (45.5%). These occurred at all ages, but their frequency was
      higher in children aged between 13 and 24 months. The prevalence of mild injury
      was higher when the cause was a fall from one's own height. No differences were
      detected in severity according to the place of occurrence and witnesses of the
      accident. The prevalence of severe injury was higher in cases where three or more
      teeth were involved. CONCLUSIONS: In this specialist treatment centre, severe
      injuries were the most common TDIs, which occurred in children aged 13-24 months,
      mainly due to falls and most occurred at home. Professionals must be prepared to
      deliver the best and most efficient care to this population.

PMID- 23856809
TI  - Malocclusion in preschool children: prevalence and determinant factors.
AB  - PURPOSE: To evaluate the prevalence of malocclusion and associated factors in the
      primary dentition of preschoolers in the city of Diamantina, Brazil. METHODS: A
      cross-sectional study was carried out with 381 children aged 3-5 years treated at
      the 10 basic health care units in the city during immunisation campaigns. The
      dependent variables (presence of malocclusion, open bite, crossbite and crowding)
      were evaluated through a clinical oral exam. The independent variables (gender,
      age, health problems, breastfeeding, bottle feeding, harmful oral habits,
      mother's schooling, household income and number of children in the home) were
      collected through interviews. Statistical analysis involved descriptive analysis,
      Chi square test and Poisson regression. RESULTS: The prevalence of malocclusion
      was 32.5%. Open bite was the most frequent type of malocclusion. Children with a
      history of bottle feeding (PR 1.74; 95% CI 1.24-2.44) and those with harmful oral
      habits (PR 1.49; 95% CI 1.23-1.99) had greater prevalence rates of malocclusion.
      Greater prevalence rates of open bite were also found in children with a history
      of bottle feeding (PR 5.00; 95% CI 1.99-12.5) and those with harmful oral habits
      (PR 2.90; 95% CI 1.59-5.29), whereas greater prevalence rates of crossbite were
      found in boys (PR 1.79; 95% CI 1.10-2.91) and were associated with mother's
      schooling (PR 1.91; 95% CI 1.20-3.06). CONCLUSION: A history of bottle feeding
      and the presence of harmful oral habits were identified as determinants for the
      occurrence of malocclusion in preschoolers.

PMID- 23856810
TI  - Biogeochemical responses to nutrient inputs in a Cuban coastal lagoon: runoff,
      anthropogenic, and groundwater sources.
AB  - Laguna Larga, a coastal lagoon in central Cuba, has been heavily altered by
      tourism infrastructure construction and sewage disposal. We hypothesize that this
      has decreased the circulation and caused eutrophication of the lagoon. To assess
      this, 12 bimonthly samplings were carried out in 2007-2008. Temperature,
      salinity, oxygen, nutrients and nitrogen, and phosphorous fractions (inorganic,
      organic, and total) were determined. Water and salt budgets, as well as
      biogeochemical fluxes of nitrogen and phosphorus were calculated using the LOICZ
      budget model for the three sections of the lagoon identified by morphological
      constrains and salinity patterns. Laguna Larga is a choked lagoon with restricted
      water circulation, low exchange, and high residence times that vary significantly
      along its sections. Residence time was estimated to be 0.1-0.7 years for the
      inner section and 1-9 days for the outer one. High levels of total nitrogen
      (annual means 126-137 MUM, peaks up to 475 MUM) and phosphorus (2.5-4.4 MUM,
      peaks up to 14.5 MUM) are evidence of eutrophication of Laguna Larga. During
      2007, an average precipitation year, Laguna Larga exported water (703 m(3) d(-1))
      and was a source of nitrogen (9.026 mmol m(-2) d(-1)) and phosphorus (0.112 mmol
      m(-2) d(-1)) to the adjacent sea. delta(15)N determinations in the seagrass
      Thalassia testudinum (-1.83 to +3.02 0/00) differed significantly between sites
      in the lagoon and offshore reference sites located W of the inlet, but were
      similar to those located E of the inlet. delta(15)N determinations in the seaweed
      Penicillus dumetosus (+1.02 to +4.2) did not show significant differences.

PMID- 23856811
TI  - cDNA sequence encoding metallothionein protein from Aegiceras corniculatum and
      its gene expression induced by Pb2+ and Cd2+ stresses.
AB  - Constructing various green wetland examples for mangrove wetland systems is a
      useful way to use natural power to remediate the polluted wetlands at intertidal
      zones. Metallothioneins (MT) are involved in heavy metal tolerance, homeostasis,
      and detoxification of intracellular metal ions in plants. In order to understand
      the mechanism of heavy metal uptake in Aegiceras corniculatum, we isolated its
      metallothionein gene and studied the MT gene expression in response to heavy
      metals contamination. Here, we report the isolation and characterization of MT2
      genes from young stem tissues of A. corniculatum growing in the cadmium (Cd) and
      lead (Pb) polluted wetlands of Quanzhou Bay, southeast of China. The obtained
      cDNA sequence of MT is 512 bp in length, and it has an open reading frame
      encoding 79 amino acid residues with a molecular weight of 7.92 kDa and the
      theoretical isoelectric point of 4.55. The amino acids include 14 cysteine
      residues and 14 glycine residues. It is a non-transmembrane hydrophilic protein.
      Sequence and homology analysis showed the MT protein sequence shared more than
      60% homology with other plant type 2 MT-like protein genes. The results suggested
      that the expression level of MT gene of A. corniculatum young stems induced by a
      certain range concentration of Cd(2+) and Pb(2+) stresses (0.2 mmol L(-1) Pb(2+),
      1 mmol L(-1) Pb(2+), 0.2 mmol L(-1) Pb(2+), and 40 MUmmol L(-1) Cd(2+); 1 mmol L(
      1) Pb(2+) and 40 MUmol L(-1) Cd(2+)) compared with control might show an adaptive
      protection. The expression levels of MT gene at 20 h stress treatment were higher
      than those at 480 h stress treatment. The expression levels of MT gene with 0.2
      mmol L(-1) Pb(2+) stress treatment were higher than those with 0.2 mmol L(-1)
      Pb(2+) and 40 MUmol L(-1) Cd(2+) stress treatment, and the MT gene expression
      levels with 1 mmol L(-1) Pb(2+) treatment were higher than those with 1 mmol L(
      1) Pb(2+) and 40 MUmol L(-1) Cd(2+) treatment. There exists an antagonistic
      action between Pb(2+) and Cd(2+) in the MT metabolization of A. corniculatum.

PMID- 23856812
TI  - Composition and sources of aliphatic lipids and sterols in sediments of a
      tropical island, southern South China Sea: preliminary assessment.
AB  - Near-shore surface sediment was collected from five stations off Redang Island
      located on the eastern coast of Peninsular Malaysia. Freeze-dried sediments were
      Soxhlet extracted and then fractionated using column chromatography into
      aliphatic and polar fractions. Determination of these fractions was carried out
      using gas chromatography mass spectrometry. The concentration of total resolved
      aliphatic hydrocarbons in sediments ranged from 157 to 308 ng/g. The distribution
      of aliphatic fraction showed the presence of n-alkanes ranging from nC15 to nC33
      with a minor odd-to-even predominance exhibiting carbon maximum, depending on
      station, at nC17, nC26, nC29 or nC31. Calculation of Carbon Preference Index
      (CPI) for CPI(15-33) gave values ranging from 1.09 to 1.46. n-Alkanol in all
      sediment exhibits even-to-odd carbon predominance ranging from nC16 to nC28 and
      maximising at nC22. n-Fatty acids distribution ranged from nC14 to nC24 with a
      dominant maximum at nC16 and exhibiting high values of short chain fatty acids
      (<=nC20) to long chain fatty acids (>nC20) ratios. Unsaturated fatty acids,
      particularly nC16:1 and nC18:1 is also ubiquitous in all samples. Cholesterol is
      the most abundant compound amongst the sterol group ranging from 42.8 to 62.6% of
      the total sterols. beta-Sitosterol, brassicasterol and stigmasterol, are also
      present but of relatively lower amount. These observations suggest that the
      aliphatic lipids and sterols in the study area originate, mainly, from biogenic
      sources of marine microbial with minor contribution from epiticular waxes of
      terrestrial plants.

PMID- 23856813
TI  - Phytoextraction and phytostabilization potential of plants grown in the vicinity
      of heavy metal-contaminated soils: a case study at an industrial town site.
AB  - With the development of urbanization and industrialization, soils have become
      increasingly polluted by heavy metals. Phytoremediation, an emerging cost
      effective, nonintrusive, and aesthetically pleasing technology that uses the
      remarkable ability of plants to concentrate elements, can be potentially used to
      remediate metal-contaminated sites. In this research, two processes of
      phytoremediation (phytoextraction and phytostabilization) were surveyed in some
      plant species around an industrial town in the Hamedan Province in the central
      western part of Iran. To this purpose, shoots and roots of the seven plant
      species and the associated soil samples were collected and analyzed by measuring
      Pb, Fe, Mn, Cu, and Zn concentrations using ICP-AES and then calculating the
      biological absorption coefficient, bioconcentration factor, and translocation
      factor parameters for each element. The obtained results showed that among the
      collected plants, Salsola soda is the most effective species for phytoextraction
      and phytostabilization and Cirsium arvense has the potential for
      phytostabilization of the measured heavy metals. 

PMID- 23856814
TI  - LC-MS/MS analysis of canine lipoproteins fractionated using the
      ultracentrifugation-precipitation method.
AB  - Due to the lack of a gold standard method in canine lipoprotein analysis, it is
      unclear whether canine high-density lipoprotein (HDL) and low-density lipoprotein
      (LDL) can be accurately evaluated by the lipoprotein analysis methods used for
      dogs. This study investigated whether the ultracentrifugation-precipitation (U-P)
      method was suitable as a gold standard method for analyzing canine lipoprotein.
      First, the U-P method was compared with a gel permeation high-performance liquid
      chromatography system (GP-HPLC). The concentrations of canine HDL cholesterol
      (HDL-C) and LDL cholesterol (LDL-C) determined by the U-P method correlated
      closely with those determined by GP-HPLC. However, the canine HDL-C concentration
      determined by the U-P method was lower than that determined by GP-HPLC, and the
      canine LDL-C concentration determined by the U-P method was higher than that
      determined by GP-HPLC. This study showed that some canine HDL could be
      precipitated with heparin manganese chloride solution. Second, the HDL and LDL
      fractions separated by the U-P method were analyzed by LC-MS/MS. The HDL fraction
      was found to contain only apolipoprotein A-I, which is an apolipoprotein of HDL,
      whereas the LDL fraction contained both apolipoprotein A-I and apolipoprotein B
      100, which is an apolipoprotein of LDL. This data showed that a certain
      lipoprotein that includes apolipoprotein A-I might precipitate with canine LDL
      when using heparin manganese chloride solution. These results indicated that the
      U-P method is not currently a gold standard method for analyzing canine
      lipoproteins. 

PMID- 23856815
TI  - Acute changes in central corneal thickness according to experimental adjustment
      of intraocular pressure in normal canine eyes.
AB  - Central corneal thickness (CCT) can be a promising source of glaucoma monitoring
      and diagnosis. This study evaluated changes in CCT according to experimental
      adjustment of intraocular pressure (IOP) in canine eyes. To adjust and measure
      IOP, each eye was cannulated with two 26-gauge needles under inhalant anesthesia.
      One needle was connected to a pressure transducer, and the other was connected to
      an adjustable bag of physiologic saline. IOP was stepwise increased from 10 mmHg
      to 70 mmHg in 10 mmHg increments (Group T). IOP was maintained at 15 mmHg (Group
      C15), 30 mmHg (Group C30), 45 mmHg (Group C45), 60 mmHg (Group C60) and 75 mmHg
      (Group C75) during the experiment. CCT was measured with an ultrasonic pachymeter
      every 10 min after cannulation. There was a significant difference in the effect
      of time on CCT (P<0.001) and difference in CCT (dCCT; P<0.001) between groups.
      The CCT of group C15 remained constant during the experiment. However, group T
      showed an initial decrease and then an increase after passing the lowest point.
      Group C30 showed decreasing values for 30 min, after which the values remained
      constant. The values in Group C45 showed no changes for 40 min and then
      increased. The values in group C60 showed no change for 20 min and then
      increased. Group C75 showed a steady increase. In conclusion, the CCT showed two
      core changes according to increased IOP. This study provides essential basic data
      to enable further investigation into the association of IOP and CCT in dogs. 

PMID- 23856816
TI  - Photophysical behaviour of cyclometalated iridium(III) complexes with
      phosphino(terthiophene) ligands.
AB  - Six new Ir(III) complexes containing the 3'-phosphino-2,2':5',2''-terthiophene
      (PT3) ligand in three different coordination modes are reported. The electronic
      properties of the complexes are characterized by cyclic voltammetry, absorption,
      emission and time-resolved transient absorption spectroscopies and DFT/TDDFT
      calculations. The electrochemical and photophysical behaviour of the complexes
      was found to be dominated by the PT3 ligand. For the complexes in which the PT3
      ligand is coordinated in a bidentate P,S or P,C mode, the lowest energy
      absorption band is attributed to pi-pi* PT3 localized transitions consistent with
      observations from DFT calculations. Emission quantum yields are low in all cases
      (<0.07) and emission lifetimes are short (<50 ns). Intersystem crossing leads to
      a long-lived triplet state ((3)L) also localized on the PT3 group. In the complex
      where the PT3 ligand is coordinated only via the phosphine, TDDFT calculations
      suggest that there is some MLCT (and Cl-PT3 CT) character in the lowest energy
      transition. 

PMID- 23856817
TI  - Immunotherapy: Modified proinsulin to treat T1DM.

PMID- 23856818
TI  - Nutrition: Risk of T1DM increases with early and late weaning.

PMID- 23856819
TI  - Metabolism: Adiponectin---a mediator of specific metabolic actions of FGF21.

PMID- 23856821
TI  - Device therapy: Automatic insulin-pump suspension reduces hypoglycaemia.

PMID- 23856820
TI  - Testicular function and bone metabolism--beyond testosterone.
AB  - Findings in the past few years have advanced understanding of the crosstalk
      between testis and bone and could contribute to defining an improved clinical
      approach to the biochemical diagnosis and therapeutic management of hypogonadism
      and male osteoporosis. This Review focuses on the Leydig cells of the testis.
      Other than being responsible for steroidogenesis and production of testosterone,
      the function of these cells is fundamental to bone health in at least two other
      ways: Leydig cells produce insulin-like 3 (INSL3), which has a role in osteoblast
      function, and they contribute to 25-hydroxylation of vitamin D. Impairment of
      testicular function leads to low levels of testosterone, INSL3 and 25
      hydroxyvitamin D and consequently to an increased risk of osteopenia and
      osteoporosis.

PMID- 23856822
TI  - 18F-FDG PET/CT in a rare malignant extraskeletal osteosarcoma.
AB  - Extraskeletal osteosarcoma (EO) is a rare malignancy and its FDG PET/CT imaging
      is seldom reported. We present staging and restaging images of a FDG PET/CT
      imaging in an EO originating from paraspinous musculature. Initial staging FDG
      PET/CT scan showed increased metabolism of a mass in the right paraspinous region
      without nodal or distant metastasis. The patient underwent tumor resection and
      radiation therapy with a pathological diagnosis of EO. Restaging FDG PET/CT
      imaging demonstrated postsurgical changes without nodal or distant metastasis.
      This case demonstrates the clinical relevance of FDG PET/CT imaging for staging
      and restaging EO. 

PMID- 23856823
TI  - Incidental detection of Leydig cell tumor via fluorine-18-Choline PET/CT in a
      patient with recurrent prostate cancer disease.
AB  - We report a case of a 62-year-old man with biochemical recurrence of prostate
      cancer disease, investigated by fluorine-18-Choline ((18)F-FCH) PET/CT. (18)F-FCH
      PET/CT demonstrated focal increased uptake of (18)F-FCH inside the right testis,
      suggestive for distant recurrent disease. On testis removal, a Leydig cell tumor
      of 2.5 cm in diameter was unexpectedly found. (18)F-FCH PET/CT may demonstrate
      tumors other than prostate cancer.

PMID- 23856824
TI  - 18F-DOPA PET/CT in the evaluation of hereditary SDH-deficiency paraganglioma
      pheochromocytoma syndromes.
AB  - PURPOSE: This study aims to evaluate the role of F-DOPA PET/CT in staging and
      follow-up of paraganglioma syndromes succinate dehydrogenase (SDH)-mutation
      related patients, comparing F-DOPA PET/CT results with morphological imaging and
      biochemical results. PATIENTS AND METHODS: We retrospectively studied 10
      consecutive patients (3 F, 7 M, mean age 32 yrs), all with a genetically
      demonstrated SDH mutation (5 SDH-D, 4 SDH-B, and 1 SDH-C) and all addressed to F
      DOPA PET/CT scan. Seven patients had already been operated on for one or more
      pheochromocytomas and/or paragangliomas and were submitted to F-DOPA PET/CT scan
      according to clinical, biochemical, or radiological suspicion of recurrence,
      while 3 were only genetically positive, with no previous symptom/sign of the
      disease. For all patients, biochemical analysis (plasma and/or urinary
      catecholamine) and results of high-resolution morphological imaging studies (CT
      and/or MRI) were available. Histologic/cytologic findings or imaging and
      biochemical follow-up were taken as gold standard in all cases. RESULTS: Seven
      out of 10 patients showed one or more areas of pathological F-DOPA accumulation.
      PET/CT demonstrated the presence of the disease in 4/6 patients with no increase
      in catecholamine levels ("biochemically silent"). Positive detection rate was
      100% in SDH-D and 40% in "non-SDHD". Analyzing per lesion, F-DOPA PET/CT
      demonstrated more lesions than anatomical imaging (16 vs. 7) especially in head
      and neck paragangliomas. CONCLUSIONS: F-DOPA PET/CT seems to be the more accurate
      method for staging and restaging patients with SDH-mutations-related
      paraganglioma syndromes. F-DOPA is particularly useful in detecting head and neck
      and biochemically silent paragangliomas, and also in apparently healthy mutation
      carrying people.

PMID- 23856825
TI  - Prognostic predictive value of total lesion glycolysis from 18F-FDG PET/CT in
      post-surgical patients with epithelial ovarian cancer.
AB  - PURPOSE: The aim of this study was to determine an optimal threshold method for
      the segmentation of malignant lesions from (18)F-FDG PET/CT images and to
      evaluate the prognostic value of the total lesion glycolysis in post-surgical
      patients with epithelial ovarian cancer. METHODS: We retrospectively reviewed 47
      patients with pathologically proven epithelial ovarian cancer who underwent (18)F
      FDG PET/CT imaging after surgery. The follow-up time was 26.6 +/- 19.8 months
      (ranged from 4 to 89 months). For each patient, every lesion was segmented by 2
      thresholds with 3D-area growing algorithm, standard uptake value (SUV) 2.5, and
      background method. The detection rates were compared. The optimal threshold
      method was then used to calculate whole-body metabolic tumor volume (WBMTV) and
      whole-body total lesion glycolysis (WBTLG). The prognostic significance of
      SUV(max), WBMTV, WBTLG, and other pathological variables for overall survival
      were assessed by Cox proportional hazards regression analysis and Kaplan-Meier
      survival analysis. RESULTS: A total of 142 metastatic lesions of 47 patients were
      confirmed by long-term clinical follow-up or pathological findings. The detection
      rates of the threshold SUV 2.5 and background methods were 37.32% (53/142) and
      96.48% (137/142), respectively, which showed significant difference between the 2
      methods (P < 0.005). In multivariate analysis, WBTLG, obtained from the
      background method, was an independent predictive factor associated with the
      prognosis (HR 1.043, 95% CI 1.01-1.078, P = 0.011), and none of the other factors
      had statistical association. Survival analysis also showed that the survival time
      was clearly shortened with WBTLG increasing (P < 0.001). CONCLUSIONS: In this
      group of post-surgery patients with epithelial ovarian cancer, the background
      method could segment much more malignant lesions than SUV = 2.5 method, and
      WBTLG, obtained from this method, could be used as an independent prognostic
      factor.

PMID- 23856826
TI  - Thyroid lymphoma incidentally detected by 18F-fluorocholine (FCH) PET/CT.
AB  - A 63-year-old man underwent a (18)F-fluorocholine ((18)F-FCH) PET/CT for staging
      assessment of a high-risk locally advanced prostate cancer with an equivocal node
      on conventional workup (Gleason 4 + 5, PSA 11.1; T3b, N(0/1), M(0) on standard
      staging investigations). (18)F-FCH-avid disease was demonstrated in the prostate
      and several non-enlarged pelvic nodes. An incidental focus of tracer uptake was
      reported within the left lobe of the thyroid gland, with subtle enlargement of
      the left thyroid lobe on the CT component of the study. A diagnosis of diffuse
      large B-cell lymphoma was confirmed following thyroid ultrasound and cytology.

PMID- 23856827
TI  - Gallbladder carcinoma metastasizing to adrenal gland: a rare site demonstrated
      with (18)F-FDG PET/CT.
AB  - Adrenal metastases have commonly been reported in a wide variety of cancers but
      not in gallbladder cancer. We here present a case of a 45-year-old male patient
      with gallbladder carcinoma where left adrenal metastasis was detected on staging
      F-FDG PET/CT. This was confirmed histopathologically. F-FDG PET/CT can have a
      significant impact on management of patients with gallbladder carcinoma by
      demonstrating rare sites of metastasis. 

PMID- 23856828
TI  - CT, MRI, and FDG PET/CT in a patient with alveolar soft part sarcoma.
AB  - Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor. We
      present a case, who had a history of a left pulmonary ASPS resection 5 years ago,
      with a tumor in the left lower extremity showing high vascularity mimicking
      hemangioma on enhanced CT and MRI. This tumor showed intense FDG uptake on FDG
      PET/CT with SUVmax of 6.8, indicating a malignant soft tissue tumor. Complete
      resection of the tumor was performed. A diagnosis of ASPS was confirmed by
      pathology. This case highlights FDG PET/CT is helpful for differentiating ASPS
      from hemangioma according the degree of FDG uptake. 

PMID- 23856829
TI  - FDG PET/CT in endobronchial metastases from extrathoracic malignancies.
AB  - Metastasis to the bronchus from extrathoracic malignancy is a rare event. We
      present 2 cases of endobronchial metastases from extrathoracic tumors with FDG
      PET/CT findings. One patient had a hypermetabolic endobronchial metastasis from
      breast cancer. The other patient had a hypermetabolic endobronchial metastasis
      from hepatocellular carcinoma. Both the endobronchial metastases were confirmed
      by bronchoscopic biopsy. These 2 cases indicate that FDG PET/CT is useful for
      detecting endobronchial metastases, and endobronchial metastasis should be
      included in the differential diagnosis of abnormal endotracheal or endobronchial
      FDG accumulation in patients with histories of malignant tumors. 

PMID- 23856830
TI  - Amyloid PET/MRI in the differential diagnosis of dementia.
AB  - The potential of brain imaging has grown rapidly with new modalities, hybrid
      combinations of existing modalities, and novel metabolic tracers. F-florbetapir
      is an amyloid plaque-binding molecule labeled to F that allows positron imaging
      of the amyloid deposition in the brain. This protein deposition is known to be
      one of the features in Alzheimer disease and therefore can be of interest in the
      differential diagnosis of dementia. We present 2 cases combining the new hybrid
      imaging modality PET/MRI, which offers molecular and morphological information,
      with F-florbetapir in the differential diagnosis of dementia. 

PMID- 23856831
TI  - An unusual orbital localization of wegener granulomatosis detected by 18F-FDG
      PET/CT.
AB  - We report a case of a 61-year-old male patient affected by Wegener granulomatosis
      and left exophthalmos who underwent F-FDG PET/CT during follow-up for rectal
      cancer. The study was negative for secondary lesions but revealed high uptake at
      the left orbital mass consistent with Wegener granulomatosis. 

PMID- 23856832
TI  - Searching for a neurobiological basis for self-medication theory in ADHD comorbid
      with substance use disorders: an in vivo study of dopamine transporters using
      (99m)Tc-TRODAT-1 SPECT.
AB  - PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) and substance use
      disorders (SUD) frequently co-occur. Although several studies have shown changes
      in striatal dopamine transporter (DAT) density in these disorders, little is
      known about the neurobiological basis of the comorbidity. The aim of this study
      was to evaluate striatal DAT density in treatment-naive ADHD adolescents with SUD
      (ADHD + SUD) and without SUD (ADHD), compared to SUD adolescents without ADHD
      (SUD) and healthy control subjects (HC). PATIENTS AND METHODS: Sixty-two male age
      matched subjects diagnosed with DSM-IV criteria were included: ADHD + SUD (n =
      18), SUD (n = 14), HC (n = 19), and ADHD (n = 11). Urine tests confirmed
      participants' drug use. All subjects performed SPECT scans with Tc-TRODAT-1 to
      evaluate DAT density in the striatum. RESULTS: The mean right striatum specific
      binding were 1.68 (ADHD), 1.38 (ADHD + SUD), 1.19 (HC), 1.17 (SUD), and in left
      striatum 1.65 (ADHD), 1.39 (ADHD + SUD), 1.19 (HC), and 1.17 (SUD). The ADHD
      group presented significantly higher striatal DAT density compared with ADHD +
      SUD, SUD, and HC groups. Adolescents with ADHD + SUD had significantly lower DAT
      density than those with ADHD, but significantly higher DAT density than those
      with SUD only and no significant difference from the healthy control group.
      CONCLUSION: The ADHD + SUD group had lower striatal DAT density in comparison
      with ADHD without SUD. It is possible to speculate that the use of cannabis and
      cocaine is responsible for the lower striatal DAT density in this group which
      would help in understanding the neurobiological basis for the self-medication
      theory in ADHD adolescents.

PMID- 23856833
TI  - Microvascular anastomosis guidance and evaluation using real-time three
      dimensional Fourier-domain Doppler optical coherence tomography.
AB  - Vascular and microvascular anastomoses are critical components of reconstructive
      microsurgery, vascular surgery, and transplant surgery. Intraoperative surgical
      guidance using a surgical imaging modality that provides an in-depth view and
      three-dimensional (3-D) imaging can potentially improve outcome following both
      conventional and innovative anastomosis techniques. Objective postoperative
      imaging of the anastomosed vessel can potentially improve the salvage rate when
      combined with other clinical assessment tools, such as capillary refill,
      temperature, blanching, and skin turgor. Compared to other contemporary
      postoperative monitoring modalities--computed tomography angiograms, magnetic
      resonance (MR) angiograms, and ultrasound Doppler--optical coherence tomography
      (OCT) is a noninvasive high-resolution (micron-level), high-speed, 3-D imaging
      modality that has been adopted widely in biomedical and clinical applications.
      For the first time, to the best of our knowledge, the feasibility of real-time 3
      D phase-resolved Doppler OCT (PRDOCT) as an assisted intra- and postoperative
      imaging modality for microvascular anastomosis of rodent femoral vessels is
      demonstrated, which will provide new insights and a potential breakthrough to
      microvascular and supermicrovascular surgery.

PMID- 23856834
TI  - Transcutaneous delivery of micro- and nanoparticles with laser microporation.
AB  - Fractional laser ablation is one of the relatively safe and minimally invasive
      methods used to administer micro- and nanoparticles into the skin at sufficiently
      large depth. In this article, we present the results of delivery of TiO2
      nanoparticles and Al2O3 microparticles into skin. Fractional laser microablation
      of skin was provided by a system based on a pulsed Er:YAG laser with the
      following parameters: the wavelength 2940 nm, the pulse energy 3.0 J, and the
      pulse duration 20 ms. Ex vivo and in vivo human skin was used in the study. The
      suspensions of titanium dioxide and alumina powder in polyethylene glycol with
      particle size of about 100 nm and 27 MUm, respectively, were used. In the ex vivo
      experiments, reflectance spectra of skin samples with administered particles were
      measured and histological sections of the samples were made. In the in vivo
      experiment, reflectance spectroscopy, optical coherence tomography, and clinical
      photography were used to monitor the skin status during one month after
      suspension administering. It is shown that particles can be delivered into dermis
      up to the depth 230 MUm and distributed uniformly in the tissue. Spectral
      measurements confirm that the particles stay in the dermis longer than 1 month.

PMID- 23856835
TI  - The prognostic role of claudins in head and neck squamous cell carcinomas.
AB  - The expression of tight junction proteins is frequently altered in epithelial
      cancers. The loss of cell-cell adhesion associates with enhanced metastatic
      potential, which underlies the role of altered expression pattern of tight
      junction component claudins (CLDNs). Our study assessed the expression of CLDN 1,
      2, 3, 4, 7, 8 and 10 in squamous cell carcinoma of the head and neck region
      (HNSCC) including oropahrynx, larynx, and hypopharynx in comparison to normal
      epithelial tissue of the same patient. The surgical samples were examined by
      tissue microarray and immunohistochemistry, the expression was calculated by H
      score, which took account of intensity and percentage of positivity as well. Both
      normal and cancerous tissue proved negative for CLDN 3, 8 and 10. Normal
      epithelia showed mild expression of CLDN 4, but the minimal positivity
      disappeared in squamous cancer. In case of CLDN 1 and CLDN 7 we demonstrated
      significantly increased intensity in cancer, while CLDN 2 showed decreased
      expression compared with normal epithelium. The normal polarity and distribution
      of claudins were lost in HNSCC. Moreover, preserved expression of CLDN 2 (but not
      that of 1 and 7) was associated with better survival, which suggested a potential
      prognostic role of CLDN 2. 

PMID- 23856836
TI  - Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a
      skin immune system with features of "inflamm-aging".
AB  - Dendritic cells (DC) are central in regulating skin immunity. Immunosenescence is
      associated with a chronic inflammatory state. Little is known about the
      contribution of DC to "inflamm-aging". When determining langerhans cell (LC)
      numbers, we found a 60 % reduction of LC in aged epidermis. Reactive oxygen
      species(ROS) are linked with aging. The mitochondrial manganese superoxide
      dismutase (SOD2) is in the first line of antioxidant defense. We investigated the
      function of DC from SOD2 heterozygous mice (SOD2+/-) and found that at 4 months
      of age LC numbers are not altered, but activated LC have impaired expression of
      MHC-II and CD44. Immature SOD2+/- DC produced increased proinflammatory IL-6 and
      chemokines CXCL1 and CXCL2. Upon challenge SOD2+/- DC accumulated ROS. When
      activating SOD2+/- DC by LPS they less efficiently upregulated MHC-II, CD86 and
      CD44. Surprisingly, in vivo contact hypersensitivity (CHS) was enhanced in SOD2+/
      mice although SOD2+/- DC were less potent in stimulating wt T cells. However,
      SOD2+/- T cells showed increased proliferation, even when stimulated with SOD2+/-
      DC, possibly explaining the increased CHS. Our findings suggest that SOD2 is a
      molecular candidate in the regulation of "inflamm-aging" conveying both
      immunosuppressive and proinflammatory signals through alteration of DC and T cell
      functions.

PMID- 23856837
TI  - p38delta mitogen-activated protein kinase regulates the expression of tight
      junction protein ZO-1 in differentiating human epidermal keratinocytes.
AB  - Increasing evidence has recognized tight junctions (TJs) as the lower epidermal
      inside-out diffusion barrier located in granular cell layers of the epidermis.
      However, little is known about the regulation of TJ components in epidermis. p38
      pathway is one of the mitogen-activated protein kinase pathways, which controls
      cell growth, differentiation, and apoptosis. We have investigated the role of p38
      signaling pathway in the regulation of selected desmosomal, adherens and TJ
      components in human primary keratinocytes during Ca(2+)-induced differentiation,
      as well as in cultured squamous cell carcinoma cell lines. p38 signaling pathway
      was inhibited in cultured keratinocytes and cutaneous squamous cell carcinoma
      cells using recombinant adenoviruses, small inhibitory RNAs (siRNA) and chemical
      inhibitors. Expression of intercellular junction proteins was investigated using
      Western analysis and indirect immunofluorescence (IIF). The results showed that
      inhibition of p38delta function by siRNA or adenovirally delivered dominant
      negative mutant led to markedly decreased levels of Zonula occludens-1 (ZO-1)
      protein in keratinocytes, while the expression of other junctional proteins
      studied was not altered. Immunolocalization of ZO-1 revealed that intercellular
      junction areas were depleted from ZO-1. Inhibition of ZO-1 by siRNA silencing did
      not however result in an altered expression or subcellular localization of other
      TJ components studied. The expression of ZO-1 in carcinoma cells was also
      regulated by p38. The results indicate that ZO-1 is regulated by p38delta while
      the other junction proteins studied are not. Since ZO-1 is an integral component
      of functional TJs, various pathological processes affecting signaling via
      p38delta may also interfere with epithelial maturation and the formation and
      function of TJs.

PMID- 23856838
TI  - A comparison of ThinPrep Imager-assisted with manual screening, and its place in
      the New Zealand cervical cancer screening program.
AB  - AIMS: Overseas studies have shown equivalent sensitivity and specificity between
      computer-assisted screening and manual screening, with increased screener
      productivity. This study was undertaken to test these in a New Zealand laboratory
      setting. METHODS: A total of 9232 slides were read manually alone, and following
      ThinPrep Imager-assisted screening, and the results compared. Two senior
      screeners and a cytopathologist reviewed the slides with discordant results.
      RESULTS: The detection rate for abnormalities was 7.30% for Imager-assisted
      screening and 7.83% for manual screening. The concordance in diagnosis of
      abnormalities ranged from 72.7% to 100% with the lowest concordance for high
      grade abnormalities diagnosed by Imager-assisted screening. The rate of
      unsatisfactory smears with Imager-assisted screening is half that of manual
      screening. There was a screener productivity increase of 140%. In all but one
      case, abnormal cells were identified by the Imager but screeners varied in their
      interpretations. CONCLUSIONS: Overall, Imager-assisted screening was as sensitive
      as manual screening, and more sensitive for high-grade lesions, with a halving of
      the rate of unsatisfactory smears. In the setting of the New Zealand cervical
      screening program, the initial screen by the Imager removes the need for a
      second, rapid rescreen required by the program for manual screening.

PMID- 23856839
TI  - Chromoblastomycosis in Australia: an historical perspective.
AB  - AIMS: To study the histological features of a large series of patients with
      chromoblastomycosis to ascertain whether the earlier presentation of patients
      with this disease has resulted in any changes in the histological features that
      were recorded over 60 years ago. METHODS: A key word search of the database of
      our pathology laboratory over the period 1 January 2004 to 30 June 2012 was
      carried out for cases reported as chromoblastomycosis. RESULTS: Seventy cases of
      chromoblastomycosis were reported over this period. A further four cases of
      subcutaneous chromomycosis were found in this search. They were excluded from the
      study because of their different aetiopathogenesis. Key histological features
      such as the presence of pseudoepitheliomatous hyperplasia, granulomas,
      suppurative granulomas, suppuration and the presence of brown (dematiaceous)
      sclerotic bodies were evaluated. Fewer cases showed pseudoepitheliomatous
      hyperplasia than in earlier studies. Sclerotic bodies were found easily in H&E
      sections in all cases, averting the need for any special stains. Only ten cases
      were submitted for culture; six grew Cladophialophora carionii and two Fonsecaea
      pedrosoi. CONCLUSIONS: Chromoblastomycosis has changed little, histologically,
      since the original descriptions over 60 years ago, despite its much earlier
      clinical presentation these days. Pseudoepitheliomatous hyperplasia was seen in
      77.1% of our cases, compared to its almost universal presence in cases reported
      many years ago that often presented after many years with the disease.

PMID- 23856840
TI  - Typing early Australian healthcare-associated MRSA: confirmation of major clones
      and emergence of ST1-MRSA-IV and novel ST2249-MRSA-III.
AB  - AIMS: To investigate the evolutionary origins of Australian healthcare-associated
      (HCA) methicillin-resistant Staphylococcus aureus (MRSA) strains from a panel of
      historical isolates typed using current genotyping techniques. METHODS: Nineteen
      MRSA isolates from 1965 to 1981 were examined and antibiotic susceptibility
      profiles determined. Genetic characterisation included real-time (RT) polymerase
      chain reaction (PCR) assays to identify single nucleotide polymorhpism (SNP)
      clonal complexes (SNP CC) and sequence type (SNP ST), multi locus sequence typing
      (MLST) and staphylococcal chromosomal cassette mec typing. RESULTS: All SNP CC30
      isolates belonged to a novel sequence type, ST2249. All SNP CC239 isolates were
      confirmed as ST239-MRSA-III, except for a new single locus variant of ST239,
      ST2275. A further new type, ST2276, was identified. CONCLUSIONS: The earliest
      MRSA examined from 1965 was confirmed as ST250-MRSA-I, consistent with archaic
      European types. Identification of ST1-MRSA-IV in 1981 is the earliest appearance
      of this clinically important lineage which manifested in Australia and the United
      States in the 1990s. A previously unknown multi-resistant clone, ST2249-MRSA-III,
      was identified from 1973. Gentamicin resistance first appeared in this novel
      strain from 1976 and not ST239 as previously suspected. Thus, ST2249 was present
      in the earliest phase of the HCA MRSA epidemic in eastern Australia and was
      perhaps related to the emergence of the globally epidemic strain ST239.

PMID- 23856841
TI  - Endotracheal angiomatoid 'malignant' fibrous histiocytoma: EWSR1 gene
      rearrangement.

PMID- 23856842
TI  - Multiple cytokine- and multiple cytokine receptor-expressing triple-hit B-cell
      lymphoma, unclassifiable, with features intermediate between diffuse large B-cell
      lymphoma and Burkitt's lymphoma.

PMID- 23856843
TI  - Primary Merkel cell neuroendocrine carcinoma of head and neck: uncommon
      manifestations.

PMID- 23856844
TI  - Endometriosis in appendix and adjacent caecum with intestinal gland
      differentiation.

PMID- 23856845
TI  - Isolated Langerhans cell histiocytosis in rectum: case report and literature
      review.

PMID- 23856846
TI  - A case of congenital solitary testicular myofibroma associated with an
      undescended testis.

PMID- 23856847
TI  - Adverse cutaneous reactions to tumour necrosis factor alpha antagonists.

PMID- 23856848
TI  - The usefulness of expert opinion in medicolegal referrals of malignant
      mesothelioma.

PMID- 23856849
TI  - Non-ionic radiologic contrast (iohexol) interferes with laboratory measurements
      of endocrine hormones.

PMID- 23856850
TI  - Evaluation of automated hepatitis C core antigen assay in occupational exposure.

PMID- 23856851
TI  - Escherichia hermannii bloodstream infection in a long-term haemodialysis patient.

PMID- 23856852
TI  - Bordetella holmesii and pertussis diagnosis.

PMID- 23856855
TI  - Evaluation of predictive tests for screening for dihydropyrimidine dehydrogenase
      deficiency.
AB  - 5-Fluorouracil (5-FU) is rapidly degraded by dihyropyrimidine dehydrogenase
      (DPD). Therefore, DPD deficiency can lead to severe toxicity or even death
      following treatment with 5-FU or capecitabine. Different tests based on assessing
      DPD enzyme activity, genetic variants in DPYD and mRNA variants have been studied
      for screening for DPD deficiency, but none of these are implemented broadly into
      clinical practice. We give an overview of the tests that can be used to detect
      DPD deficiency and discuss the advantages and disadvantages of these tests. 

PMID- 23856856
TI  - RE: The prevalence of premature ejaculation and its clinical characteristics in
      Korean men according to different definitions.

PMID- 23856854
TI  - Positive effects of methylphenidate on hyperactivity are moderated by
      monoaminergic gene variants in children with autism spectrum disorders.
AB  - Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children
      with autism spectrum disorders (ASDs), however, response and tolerability varies
      widely. We hypothesized monoaminergic gene variants may moderate MPH effects in
      ASD, as in typically developing children with attention-deficit/hyperactivity
      disorder. Genotype data were available for 64 children with ASD and hyperactivity
      who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58
      who went on to be randomized to placebo and three doses of MPH during a 4-week
      blinded, crossover study. Outcome measures included the Clinical Global
      Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC
      hyperactivity index). A total of 14 subjects discontinued the study because of
      MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A,
      SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met
      positive responder criteria. In this modest but relatively homogeneous sample,
      significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3
      (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found
      for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3
      (P<0.04) were associated with tolerability in the 14 subjects who discontinued
      the trial. For this first MPH pharmacogenetic study in children with ASD,
      multiple monoaminergic gene variants may help explain individual differences in
      MPH's efficacy and tolerability. 

PMID- 23856853
TI  - Association of a complement receptor 1 gene variant with baseline erythrocyte
      sedimentation rate levels in patients starting anti-TNF therapy in a UK
      rheumatoid arthritis cohort: results from the Biologics in Rheumatoid Arthritis
      Genetics and Genomics Study Syndicate cohort.
AB  - Eligibility for anti-tumour necrosis factor (TNF) therapy in most European
      countries is restricted to severe, active rheumatoid arthritis (RA). The DAS28
      score is a marker of disease severity and incorporates one of two inflammatory
      markers, erythrocyte sedimentation rate (ESR) or C-reactive protein. We aimed to
      determine the relation between genetic variants known to affect ESR and levels of
      ESR in patients with active RA. DNA samples were genotyped for four single
      nucleotide polymorphisms (SNPs) rs7527798 (CR1L), rs6691117 (CR1), rs10903129
      (TMEM57) and rs1043879 (C1orf63). The association between SNPs and baseline ESR,
      baseline DAS28-ESR, and change in DAS28-ESR was evaluated. Baseline ESR was
      significantly associated with CR1 rs6691117 genotype (P=0.01). No correlation was
      identified between baseline DAS28-ESR or change in DAS28-ESR. In conclusion,
      genetic variation in the gene encoding CR1 may alter ESR levels but not DAS28
      ESR, indicating no adjustment for CR1 genotype is required in the assessment of
      patients with severe active RA. 

PMID- 23856857
TI  - Differences in virulence markers between Helicobacter pylori strains from the
      Brazilian Amazon region.
AB  - INTRODUCTION: This study compares virulence markers of Helicobacter pylori
      isolated from patients in 2 cities in the Brazilian Amazon. METHODS: The study
      analyzed 168 patients with chronic gastritis from Belem and 151 from Braganca,
      State of Para, Brazil. Levels of bacterial DNA associated with cagA and vacA
      alleles were checked by PCR, and hematoxylin-eosin staining was used for
      histologic diagnosis. RESULTS: In Braganca 87% of patients were genotype s1m1
      cagA-positive (s1m1 cagA+), compared with 76% in Belem. In samples from patients
      in both cities, there was an association between s1m1 cagA+ strains and gastric
      mucosal damage. CONCLUSIONS: Both cities have a high frequency of s1m1 cagA+
      strains of H. pylori.

PMID- 23856858
TI  - Phlebotomine sandfly fauna and natural Leishmania infection rates in a rural area
      of Cerrado (tropical savannah) in Nova Mutum, State of Mato Grosso in Brazil.
AB  - INTRODUCTION: American cutaneous leishmaniasis (ACL) has been reported in every
      municipality of the State of Mato Grosso, Brazil, but the transmission
      epidemiology remains poorly understood. Our study was developed in a rural area
      of the Nova Mutum municipality where four autochthonous cases of ACL were
      reported in 2009. Our aims were to describe the local phlebotomine sandfly fauna
      and to investigate the infection rates and infecting Leishmania species in the
      captured sandflies. METHODS: Entomological captures were performed bimonthly at
      10 fixed sites close to the edge of a forested area between June 2011 and April
      2012. RESULTS: A total of 3,743 phlebotomine sandflies belonging to 31 distinct
      species were captured. Approximately 75% of the specimens were females. The most
      abundant species (45.4%) was Lutzomyia antunesi, which was consistently captured
      at every site. Species that are epidemiologically important for ACL, such as L.
      flaviscutellata, L. whitmani and L. umbratilis, were also captured. L. antunesi
      and L. ubiquitalis were naturally infected by Leishmania braziliensis or Le.
      guyanensis, with minimum infection rates of 0.88% and 6.67%, respectively.
      Surprisingly, L. antunesi was infected by Le. infantum (synonym chagasi).
      CONCLUSIONS: The natural infection of L. antunesi and L. ubiquitalis by
      Leishmania sp. suggests that these species might play a role in the zoonotic
      cycle of ACL in Nova Mutum. The presence of Le. infantum in L. antunesi suggests
      that there may be a risk of an outbreak of visceral leishmaniasis (VL) in Nova
      Mutum.

PMID- 23856859
TI  - Current epidemiological profile of Chagasic megaesophagus in Central Brazil.
AB  - INTRODUCTION: Chagasic megaesophagus (CM) is the most common digestive
      manifestation of Chagas disease in Brazil, and the State of Goias is one of the
      most affected regions. In recent decades, the Hospital das Clinicas
      (HC)/Universidade Federal de Goias (UFG) has been a reference center for the
      study and treatment of CM. The objective of this study was to characterize the
      current epidemiological profile of patients with CM observed at the HC of the UFG
      from 1998 to 2010. METHODS: In total, 939 patient records were analyzed, and age,
      gender, place of birth, serology, symptoms and radiological classification
      according to Rezende et al. were analyzed. RESULTS: The median patient age was 55
      years. Male patients were more (54%) prevalent than female patients. The
      prevalence of younger patients (less than 31 years of age) was 4.2%, but 82.1% of
      the younger patients were from State of Bahia. Patients older than 40 years were
      the majority (85.5%). The radiological groups were distributed as follows: Group
      I (35.9%), Group II (32.9%), Group III (17%) and Group IV (14.2%). CONCLUSIONS:
      Compared with previous studies by the same group in 1975, 1994 and 1995, the
      number of younger patients decreased, and the frequency curve has shifted to
      older patients.

PMID- 23856860
TI  - Factors associated with a diagnosis of major depression among HIV-infected
      elderly patients.
AB  - INTRODUCTION: Acquired immunodeficiency syndrome (AIDS) is being increasingly
      reported among the elderly and major depression (MD) may be associated with
      suboptimal adherence to treatment. METHODS: Cross-sectional study on factors
      associated with MD among 72 HIV-infected elderly individuals. RESULTS: Twenty
      (27.7%) patients were found to have MD. The female gender (odds ratio [OR] =
      10.65; p = 0.00586), a low CD4 count during the study (OR = 1.005247; p =
      0.01539), and current smoking status (OR = 12.89; p = 0.01693) were independently
      associated with MD. CONCLUSIONS: Our data underscore the need to attentively
      search and treat MD among HIV-infected elderly patients.

PMID- 23856861
TI  - Determination of germ tube, phospholipase, and proteinase production by
      bloodstream isolates of Candida albicans.
AB  - INTRODUCTION: Candida albicans is a commensal and opportunistic agent that causes
      infection in immunocompromised individuals. Several attributes contribute to the
      virulence and pathogenicity of this yeast, including the production of germ tubes
      (GTs) and extracellular hydrolytic enzymes, particularly phospholipase and
      proteinase. This study aimed to investigate GT production and phospholipase and
      proteinase activities in bloodstream isolates of C. albicans. METHODS: One
      hundred fifty-three C. albicans isolates were obtained from blood samples and
      analyzed for GT, phospholipase, and proteinase production. The assays were
      performed in duplicate in egg yolk medium containing bovine serum albumin and
      human serum. RESULTS: Detectable amounts of proteinase were produced by 97% of
      the isolates, and 78% of the isolates produced phospholipase. GTs were produced
      by 95% of the isolates. A majority of the isolates exhibited low levels of
      phospholipase production and high levels of proteinase production. CONCLUSIONS:
      Bloodstream isolates of C. albicans produce virulence factors such as GT and
      hydrolytic enzymes that enable them to cause infection under favorable
      conditions.

PMID- 23856862
TI  - The dispersion of Lutzomyia longipalpis in urban areas.

PMID- 23856863
TI  - Prevalence and factors associated with HCV infection among elderly individuals in
      a southern Brazilian city.
AB  - INTRODUCTION: Few Latin American studies have assessed the prevalence of
      hepatitis C virus (HCV) infection in elderly individuals, in whom the highest
      rates are expected. We aimed to investigate the prevalence of and factors
      associated with HCV infection in elderly residents in the municipality of
      Tubarao, Santa Catarina. METHODS: This cross-sectional study included 820
      individuals (aged >= 60 years) who were selected by simple random sampling. The
      presence of anti-HCV antibodies was tested by chemiluminescence, and HCV RNA
      detection was performed for the anti-HCV-reactive subjects. Those individuals who
      were anti-HCV reactive but had undetectable HCV RNA levels were tested using a
      third-generation recombinant immunoblot assay. The variables were compared using
      the chi-squared test or Fisher's exact test, and those variables with p < 0.05
      were included in the logistic regression model. RESULTS: The mean patient age was
      68.6 years (SD 7.0 years); 39% were men, and 92% were Caucasian. Eighteen
      subjects were anti-HCV positive. Among these individuals, 4 were characterized as
      false-positives, leaving 14 (1.7%) individuals with confirmed infections for
      analysis. HCV infection was associated with an age older than 65 years,
      households with 3 or more residents and the previous transfusion of blood
      products. In the logistic regression analysis, the following variables were
      independently associated with HCV infection: households with 3 or more residents
      (OR 7.9, 95% CI 1.7-35.9, p = 0.008) and previous blood transfusion (OR 6.2, 95%
      CI 2.1-18.6, p = 0.001). CONCLUSIONS: The HCV prevalence in the elderly
      population in the municipality of Tubarao was higher than that found in previous
      studies of blood donors in the same region. Although exposure to contaminated
      blood products remained important, other transmission routes, such as household
      transmission, could play a role in HCV infection.

PMID- 23856864
TI  - Monitoring Trypanosoma cruzi infection in triatomines using PCR in Mato Grosso do
      Sul, Brazil.
AB  - INTRODUCTION: The aim of the present study was to assess the polymerase chain
      reaction (PCR) as a method for detecting Trypanosoma cruzi infection in
      triatomines that had been previously determined by microscopic examination in the
      State of Mato Grosso do Sul, Brazil. METHODS: In total, 515 specimens were
      collected. Material from the digestive tract of each triatomine was analyzed for
      the presence of T. cruzi by microscopic examination and PCR using the 121/122
      primer set. RESULTS: Among the 515 specimens tested, 58 (11.3%) were positive by
      microscopy and 101 (19.61%) were positive by PCR and there was an association
      between the results of the techniques (chi2 = 53.354, p = 0.001). The main
      species of triatomine identified was T. sordida (95.5%) CONCLUSIONS: The use of
      PCR in entomological surveillance may contribute to a better assessment of the
      occurrence of T. cruzi in triatomine populations.

PMID- 23856865
TI  - Hodgkin lymphomas in HIV/AIDS patients when treated with combined antiretroviral
      therapy: further studies are needed for understanding the pathogenesis of
      developing Hodgkin lymphomas in HIV.

PMID- 23856866
TI  - Spontaneous reporting of adverse events following pandemic influenza A (H1N1)
      immunization in a reference center in the State of Sao Paulo, Brazil.
AB  - INTRODUCTION: This paper describes adverse events (AEs) temporally associated to
      the pandemic influenza A (H1N1) vaccine observed in a reference center in Sao
      Paulo, Brazil, during a 2010 mass vaccination campaign. METHODS: A retrospective
      study involving persons who sought medical care for AEs following influenza
      vaccination. Data were retrieved from medical records, vaccine AE notification
      forms, and a computerized system for immunobiological registration. RESULTS:
      Sixty-six vaccinees sought medical care for AEs after immunization. The most
      frequent AEs were fever, headache, myalgia, and pain at the injection site. No
      serious AEs were reported. CONCLUSIONS: Few vaccinees spontaneously reported AEs
      to influenza A (H1N1) vaccine at this center.

PMID- 23856867
TI  - Listeriosis in the far South of Brazil: neglected infection?
AB  - Listeriosis is an under-diagnosed and under-reported infection; however,
      listeriosis is not a compulsorily notifiable disease in Brazil. We provide an
      overview of the rates of listeriosis in the United States of America (USA),
      Europe, Latin America, and Brazil during the past decade. We also report a case
      of miscarriage caused by listeriosis in which there was no suspicion of this
      infection. This overview and the case we report serve as reminders of the often
      neglected threat of listeriosis and its potential to cause miscarriage while
      highlighting the necessity of recognizing listeriosis as a compulsorily
      notifiable disease in Brazil. 

PMID- 23856868
TI  - Evaluation of larvicidal activity and brine shrimp toxicity of rhizome extracts
      of Zingiber zerumbet (L.) Smith.
AB  - INTRODUCTION: In this study, we used dichloromethane (DCM) and methanol (MeOH)
      extracts of the Zingiber zerumbet rhizome to evaluate brine shrimp lethality and
      larvicidal activity on Aedes aegypti and Anopheles nuneztovari mosquitoes.
      METHODS: Bioassays were performed by exposing third-instar larvae of each
      mosquito species to the DCM or MeOH extracts. RESULTS: Probit analysis with DCM
      and MeOH extracts demonstrated efficient larvicidal activity against A. aegypti
      and A. nuneztovari larvae. CONCLUSIONS: The DCM and MeOH extracts showed higher
      activity against A. nuneztovari larvae than against A. aegypti larvae, suggesting
      that the extracts have species-specific activity.

PMID- 23856869
TI  - Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from patients
      attending a public referral center for sexually transmitted diseases in Belo
      Horizonte, State of Minas Gerais, Brazil.
AB  - INTRODUCTION: The aim of this study was to determine the antimicrobial
      susceptibility of Neisseria gonorrhoeae isolates obtained from patients attending
      a public referral center for sexually transmitted diseases and specialized care
      services (STD/SCS) in Belo Horizonte, Brazil. METHODS: Between March 2011 and
      February 2012, 201 specimens of Neisseria gonorrhoeae were consecutively obtained
      from men with symptoms of urethritis and women with symptons of cervicitis or
      were obtained during their initial consultation. The strains were tested using
      the disk diffusion method, and the minimum inhibitory concentrations of
      azithromycin, cefixime, ceftriaxone, ciprofloxacin, chloramphenicol, penicillin,
      tetracycline and spectinomycin were determined using the E-test. RESULTS: The
      specimens were 100% sensitive to cefixime, ceftriaxone and spectinomycin and
      exhibited resistances of 4.5% (9/201), 21.4% (43/201), 11.9% (24/201), 22.4%
      (45/201) and 32.3% (65/201) to azithromycin, ciprofloxacin, chloramphenicol,
      penicillin and tetracycline, respectively. Intermediate sensitivities of 17.9%
      (36/201), 4% (8/201), 16.9% (34/201), 71.1% (143/201) and 22.9% (46/201) were
      observed for azithromycin, ciprofloxacin, chloramphenicol, penicillin and
      tetracycline, respectively. The specimens had plasmid-mediated resistance to
      penicillin PPNG 14.5% (29/201) and tetracycline TRNG 11.5% (23/201). CONCLUSIONS:
      The high percentage of detected resistance to penicillin, tetracycline,
      chloramphenicol and ciprofloxacin indicates that these antibiotics are not
      appropriate for gonorrhea treatment at the Health Clinic and possibly in Belo
      Horizonte. The resistance and intermediate sensitivity of these isolates
      indicates that caution is recommended in the use of azithromycin and emphasizes
      the need to establish mechanisms for the surveillance of antimicrobial resistance
      for the effective control of gonorrhea.

PMID- 23856870
TI  - New focus of active transmission of Chagas disease in indigenous populations in
      the Peruvian Amazon basin.
AB  - INTRODUCTION: Several cases of acute Chagas disease (ACD) have been reported in
      the Peruvian Amazon basin. METHODS: The objective was to describe and investigate
      6 ACD cases in children from indigenous Amazon communities in the province of
      Datem del Maranon in Loreto department (2006-2010). RESULTS: The mean age was 3.6
      years. All patients had fever, 4/6 hepatomegaly, 2/6 splenomegaly, and 5/6 had
      trypomastigotes of Trypanosoma cruzi on thick smears. The fatality rate was
      33.3%. Rhodnius pictipes and Rhodnius robustus adults were found inside the homes
      and in the peri-domiciles. CONCLUSIONS: All cases reported were isolated cases.
      We report a new focus of ACD in indigenous populations.

PMID- 23856871
TI  - Spatial distribution of leprosy in areas of risk in Vitoria, State of Espirito
      Santo, Brazil, 2005 to 2009.
AB  - INTRODUCTION: Leprosy remains a relevant public health issue in Brazil. The
      objective of this study was to analyze the spatial distribution of new cases of
      leprosy and to detect areas with higher risks of disease in the City of Vitoria.
      METHODS: The study was ecologically based on the spatial distribution of leprosy
      in the City of Vitoria, State of Espirito Santo between 2005 and 2009. The data
      sources used came from the available records of the State Health Secretary of
      Espirito Santo. A global and local empirical Bayesian method was used in the
      spatial analysis to produce a leprosy risk estimation, and the fluctuation effect
      was smoothed from the detection coefficients. RESULTS: The study used thematic
      maps to illustrate that leprosy is distributed heterogeneously between the
      neighborhoods and that it is possible to identify areas with high risk of
      disease. The Pearson correlation coefficient of 0.926 (p = 0.001) for the Local
      Method indicated highly correlated coefficients. The Moran index was calculated
      to evaluate correlations between the incidences of adjoining districts.
      CONCLUSIONS: We identified the spatial contexts in which there were the highest
      incidence rates of leprosy in Vitoria during the studied period. The results
      contribute to the knowledge of the spatial distribution of leprosy in the City of
      Vitoria, which can help establish more cost-effective control strategies because
      they indicate specific regions and priority planning activities that can
      interfere with the transmission chain.

PMID- 23856873
TI  - Antifungal susceptibility and distribution of Candida spp. isolates from the
      University Hospital in the municipality of Dourados, State of Mato Grosso do Sul,
      Brazil.
AB  - INTRODUCTION: Hospital infections caused by Candida spp. are a leading cause of
      morbidity and mortality in hospitalized patients, particularly those that are
      critically ill or immunocompromised. In this study, the distribution of Candida
      species in isolates from the University Hospital of the Federal University at
      Grande Dourados and their in vitro susceptibility to antifungal drugs were
      analyzed. METHODS: Yeasts were phenotypically identified using classical
      methodologies. Antifungal susceptibility tests to amphotericin B and fluconazole
      were performed using the broth microdilution technique. RESULTS: A total of 50
      Candida isolates were obtained from hospitalized patients during the study
      period. We analyzed yeast isolates from urine (n=31; 62%), blood (n=12; 24%), and
      tracheal secretions (n=7; 14%). The following Candida species were identified: C.
      tropicalis (n=21; 42%), C. albicans (n=18; 36%), C. glabrata (n=10; 20%), and C.
      krusei (n=1; 2%). Antifungal susceptibility tests demonstrated that C. albicans
      was susceptible to both antifungal agents. However, 31.2% of the non-C. albicans
      Candida isolates displayed dose-dependent susceptibility to fluconazole, and 3.1%
      were resistant to amphotericin B. CONCLUSIONS: In contrast to previous reports,
      our results indicated that C. tropicalis was the most commonly isolated yeast
      species among the hospital patients. The predominance of non-C. albicans Candida
      infections confirms the importance of species-level identification for
      implementing appropriate antifungal therapies.

PMID- 23856874
TI  - Polymerase chain reaction and nested-PCR approaches for detecting Cryptosporidium
      in water catchments of water treatment plants in Curitiba, State of Parana,
      Brazil.
AB  - INTRODUCTION: Cryptosporidium is an important protozoan cause of waterborne
      disease worldwide of concern to public health authorities. To prevent outbreaks
      of cryptosporidiosis, the monitoring of this parasite in drinking water is
      necessary. In the present work, the polymerase chain reaction (PCR) and nested
      PCR techniques were used to detect Cryptosporidium in raw water from catchment
      points of four water treatment plants (WTP) in Curitiba, Parana, Brazil. METHODS:
      First, DNA extraction techniques were tested in samples containing decreasing
      amount of oocysts in reagent water, and PCR and nested-PCR with specific primers
      for 18SSU rDNA of Cryptosporidium were conducted to determine their sensitivity.
      In reagent water, a commercial extraction kit provided the best analytical
      sensitivity, and PCR and nested-PCR allowed the detection of five and two
      oocysts, respectively, with the primers XIAOR/XIAOF and XIAO1F/XIAO2R. RESULTS:
      In the spiking experiments, only the PCR with the primers AWA995F/AWA1206R was
      successful at detecting concentrations of 0.1 oocysts/mL. Two catchments samples
      of raw water and/or water sludge from four WTPs were contaminated with
      Cryptosporidium. CONCLUSIONS: The application of the techniques to monitor
      Cryptosporidium in water and detect contamination in water catchments of WTPs in
      Curitiba are discussed in the present work.

PMID- 23856875
TI  - An analysis of the spatiotemporal distribution of American cutaneous
      leishmaniasis in counties located along road and railway corridors in the State
      of Maranhao, Brazil.
AB  - INTRODUCTION: The incidence of American cutaneous leishmaniasis (ACL) is
      increasing in Latin America, especially in Brazil, where 256,587 cases were
      confirmed in the last decade. METHODS: This study used a Bayesian model to
      examine the spatial and temporal distribution of ACL cases between 2000 and 2009
      in 61 counties of State of Maranhao located along the three main road and railway
      corridors. RESULTS: During the study period, 13,818 cases of ACL were recorded.
      There was a significant decrease in the incidence of ACL in the ten study years.
      The recorded incidence rate ranged from 7.36 to 241.45 per 100,000 inhabitants.
      The relative risk increased in 77% of the counties, decreased in 18% and was
      maintained in only five counties. CONCLUSIONS: Although there was a decreased
      incidence of the disease, ACL was present in all of the examined municipalities,
      thus maintaining the risk of contracting this illness.

PMID- 23856876
TI  - Clinical and microbiological features of cryptococcal meningitis.
AB  - INTRODUCTION: In this study, the clinical features, underlying diseases and
      clinical outcomes of patients with cryptococcosis were investigated. In addition,
      a molecular analysis of the Cryptococcus neoformans species complex isolated from
      these patients was performed. METHODS: A prospective study of 62 cases of
      patients with cryptococcal infection was conducted at the Hospital de Doencas
      Tropicais de Goias Dr. Anuar Auad from 2009-2010. Cryptococcal meningitis cases
      were diagnosed by direct examination and cerebrospinal fluid (CSF) sample
      culture. The profiling of these patients was assessed. The CSF samples were
      submitted to India ink preparation and cultured on Sabouraud dextrose agar, and
      C. neoformans was identified by the production of urease, a positive
      phenoloxidase test and assimilation of carbohydrates. C. neoformans and C. gattii
      isolates were distinguished by growth on L-canavanine-glycine-bromothymol blue
      medium, and molecular analysis was conducted via PCR fingerprinting reactions
      using M13 and (GACA)4 primers. RESULTS: From the 62 patients with cryptococcosis,
      71 isolates of CSF were obtained; 67 (94.4%) isolates were identified as C.
      neoformans var. grubii/VNI, and 4 (5.6%) were identified as C. gattii/VGII. Of
      these patients, 53 had an HIV diagnosis. The incidence of cryptococcosis was
      higher among patients 20-40 years of age, with 74.2% of the cases reported in
      males. Cryptococcus-related mortality was noted in 48.4% of the patients, and the
      symptoms were altered sensorium, headache, fever and stiff neck. CONCLUSIONS: The
      high morbidity and mortality observed among patients with cryptococcosis
      demonstrate the importance of obtaining information regarding the epidemiological
      profile and clinical course of the disease in the State of Goias, Brazil.

PMID- 23856877
TI  - In vitro activity of antimicrobial combinations against multidrug-resistant
      Pseudomonas aeruginosa.
AB  - INTRODUCTION: Pseudomonas aeruginosa isolates related to nosocomial infections
      are often resistant to multiple antibacterial agents. In this study,
      antimicrobial combinations were evaluated to detect in vitro synergy against
      clinical isolates of P. aeruginosa. METHODS: Four clinical P. aeruginosa isolates
      were selected at random among other isolates from inpatients treated at the
      public University hospital in Ribeirao Preto, SP, Brazil. Two isolates were
      susceptible to imipenem (IPM-S) and several other antimicrobials, while the other
      two isolates were imipenem and multidrug resistant (IPM-R). The checkerboard
      method was used to assess the interactions between antimicrobials. RESULTS:
      Combinations of imipenem or other anti-Pseudomonas drugs with complementary
      antibiotics, such as aminoglycosides, fosfomycin and rifampin, reached synergy
      rates of 20.8%, 50%, 62.5% and 50% for the two IPM-S and two IPM-R Pseudomonas
      isolates, respectively. Imipenem, piperacillin-tazobactam and ceftazidime yielded
      a greater synergy rate than cefepime or ciprofloxacin. Synergist combinations
      were more commonly observed when the complementary drug was tobramycin (65%) or
      fosfomycin (57%). CONCLUSIONS: Some antibacterial combinations led to significant
      reductions of the minimum inhibitory concentrations of both drugs, suggesting
      that they could be clinically applied to control infections caused by multidrug
      resistant P. aeruginosa.

PMID- 23856878
TI  - Glucocorticoid-induced tumor necrosis factor receptor expression in patients with
      cervical human papillomavirus infection.
AB  - INTRODUCTION: The progression of human papillomavirus (HPV) infection in the
      anogenital tract has been associated with the involvement of cells with
      regulatory properties. Evidence has shown that glucocorticoid-induced tumor
      necrosis factor receptor (GITR) is an important surface molecule for the
      characterization of these cells and proposes that GITR ligand may constitute a
      rational treatment for many cancer types. We aimed to detect the presence of GITR
      and CD25 in cervical stroma cells with and without pathological changes or HPV
      infection to better understand the immune response in the infected tissue
      microenvironment. METHODS: We subjected 49 paraffin-embedded cervical tissue
      samples to HPV DNA detection and histopathological analysis, and subsequently
      immunohistochemistry to detect GITR and CD25 in lymphocytes. RESULTS: We observed
      that 76.9% of all samples with high GITR expression were HPV-positive regardless
      of histopathological findings. High GITR expression (77.8%) was predominant in
      samples with >= 1,000 RLU/PCB. Of the HPV-positive samples negative for
      intraepithelial lesion and malignancy, 62.5% had high GITR expression. High GITR
      expression was observed in both carcinoma and high-grade squamous intraepithelial
      lesion (HSIL) samples (p = 0.16). CD25 was present in great quantities in all
      samples. CONCLUSIONS: The predominance of high GITR expression in samples with
      high viral load that were classified as HSIL and carcinoma suggests that GITR+
      cells can exhibit regulatory properties and may contribute to the progression of
      HPV-induced cervical neoplasia, emphasizing the importance of GITR as a potential
      target for immune therapy of cervical cancer and as a disease evolution
      biomarker.

PMID- 23856879
TI  - Comparison of conventional serology and PCR methods for the routine diagnosis of
      Trypanosoma cruzi infection.
AB  - INTRODUCTION: Trypanosoma cruzi, a flagellated protozoan, is the etiologic agent
      of Chagas disease, and it is estimated that approximately 5 million people in
      Brazil are infected with this parasite. This work aimed to compare the current
      diagnostic methods for Chagas disease, including conventional serological (IFAT
      and ELISA) and molecular techniques (PCR), to introduce PCR as an auxiliary
      technique. METHODS: A total of 106 chagasic patients were evaluated: 88 from
      endemic areas of Parana, 6 from Sao Paulo, 3 from Minas Gerais, 3 from Rio Grande
      do Sul, 1 from Bahia and 5 from the Santa Catarina T. cruzi outbreak. The samples
      were analyzed by conventional serological methods (IFAT, ELISA), hemoculture and
      PCR to confirm Chagas disease. RESULTS: When IFAT was used to determine antibody
      levels, the sensitivity was 81.7% for patients with the cardiac form of the
      disease and 100% for the other clinical forms. In contrast, ELISA showed 84%
      sensitivity and 100% specificity. The use of serological and molecular techniques
      and their implications for the diagnosis of Chagas disease in non-endemics area
      are discussed. CONCLUSIONS: PCR constitutes an excellent support methodology for
      the laboratory diagnosis of Chagas disease due to its high sensitivity and
      specificity.

PMID- 23856880
TI  - Experimental infection of mice with Anisakis simplex.

PMID- 23856881
TI  - Features to validate cerebral toxoplasmosis.
AB  - INTRODUCTION: Neurotoxoplasmosis (NT) sometimes manifests unusual
      characteristics. METHODS: We analyzed 85 patients with NT and AIDS according to
      clinical, cerebrospinal fluid, cranial magnetic resonance, and polymerase chain
      reaction (PCR) characteristics. RESULTS: In 8.5%, focal neurological deficits
      were absent and 16.4% had single cerebral lesions. Increased sensitivity of PCR
      for Toxoplasma gondii DNA in the central nervous system was associated with
      pleocytosis and presence of >4 encephalic lesions. CONCLUSIONS: Patients with NT
      may present without focal neurological deficit and NT may occur with presence of
      a single cerebral lesion. Greater numbers of lesions and greater cellularity in
      cerebrospinal fluid improve the sensitivity of PCR to T gondii.

PMID- 23856882
TI  - Moral distress and its interconnection with moral sensitivity and moral
      resilience: viewed from the philosophy of Viktor E. Frankl.
AB  - The interconnection between moral distress, moral sensitivity, and moral
      resilience was explored by constructing two hypothetical scenarios based on a
      recent Swedish newspaper report. In the first scenario, a 77-year-old man,
      rational and awake, was coded as "do not resuscitate" (DNR) against his
      daughter's wishes. The patient died in the presence of nurses who were not
      permitted to resuscitate him. The second scenario concerned a 41-year-old man,
      who had been in a coma for three weeks. He was also coded as "do not resuscitate"
      and, when he stopped breathing, was resuscitated by his father. The nurses
      persuaded the physician on call to resume life support treatment and the patient
      recovered. These scenarios were analyzed using Viktor Frankl's existential
      philosophy, resulting in a conceivable theoretical connection between moral
      distress, moral sensitivity, and moral resilience. To substantiate our
      conclusion, we encourage further empirical research.

PMID- 23856883
TI  - Gonococcal endocarditis: a case report and literature review.
AB  - Gonococcal endocarditis is rarely encountered in the post-antibiotic era. This
      case report describes a case of a previously healthy male who presented with
      double quotidian fever, chills, cough, and urethral symptoms. The presence of a
      cardiac mitral valvular vegetation along with positive blood cultures for
      Neisseria gonorrhoeae were diagnostic for gonococcal endocarditis. This case was,
      to our knowledge, the first reported gonococcal endocarditis case in China. 

PMID- 23856884
TI  - Pacing-induced cardiomyopathy: pathophysiological insights through matrix
      metalloproteinases.
AB  - Pacing-induced ventricular dysfunction and pacing-induced cardiomyopathy (PiCMP)
      are recognized complications of chronic right ventricular pacing. Alterations in
      myocardial perfusion and sympathetic innervation contribute to the development of
      pacing-induced heart disease. However, it is unlikely that these are the only
      processes involved. Matrix metalloproteinases (MMPs) are proteolytic enzymes that
      degrade the collagenous extracellular matrix and play a central role in left
      ventricular remodelling during the development of heart failure. While the
      pathophysiological mechanisms and altered MMP expression that occur in chronic
      pressure overload, ischaemic and non-ischaemic dilated cardiomyopathy have been
      defined, those that occur in the clinical setting of pacing-induced ventricular
      dysfunction and PiCMP have not been reported. Here we review the clinical
      epidemiology of pacing-induced ventricular dysfunction and discuss how data
      derived from animal models provide insight into how changes in MMP expression and
      function contribute to the development of PiCMP. The review concludes by
      exploring pacing strategies that may be used to prevent pacing-induced
      ventricular dysfunction. 

PMID- 23856885
TI  - The temporary drop of serum octreotide concentration deteriorated ventricular
      tachycardia in an acromegalic patient.
AB  - Acromegaly is frequently accompanied by left ventricular hypertrophy (LVH) which
      causes ventricular dysfunction. Ventricular arrhythmia is one of the important
      complications in acromegalic patients. Hypertrophic cardiomyopathy (HCM) is
      characterized by LVH with a nondilated chamber. About 10 % of HCM evolve into
      dilated phase of HCM, which is associated with an increased incidence of
      ventricular tachycardia (VT). However there is no report about a combination of
      dilated phase of HCM and VT in acromegalic patients. Octreotide is a somatostatin
      analog that has been used for medical therapy for acromegaly. We herein report
      that the first case of the change of serum octreotide concentration affected the
      control of VT, which was induced by dilated phase of HCM. A 56-year-old Japanese
      man was referred to our hospital for treatment of acromegaly. The patient was
      diagnosed the dilated phase of HCM with sustained VT. The frequency and severity
      of VT were gradually ameliorated by subcutaneous octreotide injection. However VT
      was deteriorated when its injection was changed to octreotide long-acting release
      (LAR) injection. The temporary drop in serum octreotide concentration was known
      at the transition from subcutaneous injection to LAR injection. This clinical
      course gives us the important information that subcutaneous octreotide injection
      for two weeks should be necessary to keep serum octreotide concentration when
      switing to octreotide LAR administration in acromegalic patients with severe
      arrhythmia. 

PMID- 23856890
TI  - Regenerative medicine: Functional miniature human liver generated from stem
      cells.

PMID- 23856888
TI  - Mucins in pancreatic cancer and its microenvironment.
AB  - Pancreatic cancer remains a lethal malignancy with poor prognosis owing to
      therapeutic resistance, frequent recurrence and the absence of treatment
      strategies that specifically target the tumour and its supporting stroma.
      Deregulated cell-surface proteins drive neoplastic transformations and are
      envisioned to mediate crosstalk between the tumour and its microenvironment.
      Emerging studies have elaborated on the role of mucins in diverse biological
      functions, including enhanced tumorigenicity, invasiveness, metastasis and drug
      resistance through their characteristic O-linked and N-linked oligosaccharides
      (glycans), extended structures and unique domains. Multiple mucin domains
      differentially interact and regulate different components of the tumour
      microenvironment. This Review discusses: the expression pattern of various mucins
      in the pancreas under healthy, inflammatory, and cancerous conditions; the
      context-dependent attributes of mucins that differ under healthy and pathological
      conditions; the contribution of the tumour microenvironment in pancreatic cancer
      development and/or progression; diagnostic and/or prognostic efficacy of mucins;
      and mucin-based therapeutic strategies. Overall, this information should help to
      delineate the intricacies of pancreatic cancer by exploring the family of mucins,
      which, through various mechanisms in both tumour cells and the microenvironment,
      worsen disease outcome. 

PMID- 23856893
TI  - Transplantation: ADORA2B helps to block liver injury.

PMID- 23856894
TI  - Manganese clusters derived from 2-pyridylcyanoxime: new topologies and a large
      spin ground state in pyridyloximate chemistry.
AB  - Series of manganese clusters derived from 2-pyridylcyanoxime with Mn3(II) (1),
      Mn4(II) (2a, b), Mn(II)4Mn(III)4 (3), Mn(II)2Mn(III)6Mn(IV)2 (4) and
      Mn(II)3Mn(III)6Mn(IV) (5) cores have been characterized. Dc magnetic measurements
      reveal antiferromagnetic coupling for 1-4 and dominant ferromagnetic interactions
      for 5 which shows the largest ground state reported to date in pyridyloximate
      chemistry (S = 14).

PMID- 23856892
TI  - Molecular imaging in gastroenterology.
AB  - Molecular imaging is a novel field in gastroenterology that uses fluorescently
      labelled probes to specifically highlight neoplastic lesions on the basis of
      their molecular signature. The development of molecular imaging has been driven
      by the need to improve endoscopic diagnosis and by progress in targeted therapies
      in gastrointestinal oncology to provide individualized treatment, which coincides
      with progress in endoscopy techniques and further miniaturization of detection
      devices. Different exogenous molecular probes for imaging include labelled
      antibodies, oligopeptides, affibodies(TM) (Affibody AB, Bromma, Sweden), aptamers
      and activatable probes. Molecular imaging has been evaluated in two major
      indications: many trials have studied molecular imaging as a red flag technique
      to improve detection of lesions in wide-field imaging; on the other hand,
      microscopic analysis has been investigated for in vivo characterization of the
      molecular fingerprint of tumours with the ultimate goal of assessing the
      likelihood of response to targeted therapy. This Review focusses on the
      applications of molecular imaging that have immediate potential for translational
      science or imminent transition into clinical practice of gastrointestinal
      endoscopy. 

PMID- 23856895
TI  - Continuous control of tracheal cuff pressure for the prevention of ventilator
      associated pneumonia in critically ill patients: where is the evidence?
AB  - PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is a major cause of
      death, morbidity and costs in ICUs. Several evidence-based clinical interventions
      have been increasingly described for its prevention. However, continuous control
      of tracheal cuff pressure (Pcuff) is rarely mentioned in the latest clinical
      guidelines. This review focuses on the available data about the management of
      Pcuff in the ICU, including discontinuous and continuous control, and its impact
      on the prevention of VAP. RECENT FINDINGS: Current discontinuous monitoring and
      adjustment of Pcuff, even well performed, is inaccurate in maintaining Pcuff in
      the target range. Underinflation (Pcuff<20 cmH2O) of tracheal cuff is an
      independent risk factor for VAP through microaspiration of contaminated
      subglottic secretions into the lower respiratory tract. Two main types of
      devices, electronic and pneumatic, have been developed for the continuous control
      of Pcuff. Both have shown effectiveness in maintaining Pcuff in recommended range
      in ICU patients, but only the pneumatic device has provided a reduction in
      microaspiration and VAP incidence. SUMMARY: Continuous controllers of Pcuff
      represent effective, easy to use and timesaving devices in today's busy ICU
      environment. However, further studies are required to determine the impact of
      continuous control of Pcuff on VAP incidence, patient outcomes, antimicrobial
      consumption and to compare pneumatic and electronic devices, before generalizing
      their use in routine practice.

PMID- 23856896
TI  - Selected insights from application of whole-genome sequencing for outbreak
      investigations.
AB  - PURPOSE OF REVIEW: The advent of high-throughput whole-genome sequencing has the
      potential to revolutionize the conduct of outbreak investigation. Because of its
      ultimate resolution power for differentiating between closely related pathogen
      strains, whole-genome sequencing could augment the traditional epidemiologic
      investigations of infectious disease outbreaks. RECENT FINDINGS: The combination
      of whole-genome sequencing and intensive epidemiologic analysis provided new
      insights on the sources and transmission dynamics of large-scale epidemics caused
      by Escherichia coli and Vibrio cholerae, nosocomial outbreaks caused by
      methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Mycobacterium
      abscessus, community-centered outbreaks caused by Mycobacterium tuberculosis, and
      natural disaster-associated outbreaks caused by environmentally acquired molds.
      SUMMARY: When combined with traditional epidemiologic investigation, whole-genome
      sequencing has proven useful for elucidating the sources and transmission
      dynamics of disease outbreaks. Development of a fully automated bioinformatics
      pipeline for the analysis of whole-genome sequence data is much needed to make
      this powerful tool more widely accessible.

PMID- 23856898
TI  - Oxidative stress response elicited by mitochondrial dysfunction: implication in
      the pathophysiology of aging.
AB  - Under normal physiological conditions, reactive oxygen species (ROS) serve as
      'redox messengers' in the regulation of intracellular signalling, whereas excess
      ROS may induce irreversible damage to cellular components and lead to cell death
      by promoting the intrinsic apoptotic pathway through mitochondria. In the aging
      process, accumulation of mitochondria DNA mutations, impairment of oxidative
      phosphorylation as well as an imbalance in the expression of antioxidant enzymes
      result in further overproduction of ROS. This mitochondrial dysfunction-elicited
      ROS production axis forms a vicious cycle, which is the basis of mitochondrial
      free radical theory of aging. In addition, several lines of evidence have emerged
      recently to demonstrate that ROS play crucial roles in the regulation of cellular
      metabolism, antioxidant defence and posttranslational modification of proteins.
      We first discuss the oxidative stress responses, including metabolites
      redistribution and alteration of the acetylation status of proteins, in human
      cells with mitochondrial dysfunction and in aging. On the other hand, autophagy
      and mitophagy eliminate defective mitochondria and serve as a scavenger and
      apoptosis defender of cells in response to oxidative stress during aging. These
      scenarios mediate the restoration or adaptation of cells to respond to aging and
      age-related disorders for survival. In the natural course of aging, the
      homeostasis in the network of oxidative stress responses is disturbed by a
      progressive increase in the intracellular level of the ROS generated by defective
      mitochondria. Caloric restriction, which is generally thought to promote
      longevity, has been reported to enhance the efficiency of this network and
      provide multiple benefits to tissue cells. In this review, we emphasize the
      positive and integrative roles of mild oxidative stress elicited by mitochondria
      in the regulation of adaptation, anti-aging and scavenging pathway beyond their
      roles in the vicious cycle of mitochondrial dysfunction in the aging process. 

PMID- 23856897
TI  - Peptide and protein-based inhibitors of HIV-1 co-receptors.
AB  - Human immunodeficiency virus (HIV) afflicts an estimated 30 million people
      globally, making it a continuing pandemic. Despite major research efforts, the
      rate of new infections has remained relatively static over time. This article
      reviews an emerging strategy for the treatment of HIV, the inhibition of the co
      receptors necessary for HIV entry, CCR5 and CXCR4. The aim of this article is to
      highlight potential therapeutics derived from peptides and proteins that show
      particular promise in HIV treatment. Molecules that act on CCR5, CXCR4 or on both
      receptors will be discussed herein.

PMID- 23856899
TI  - Molecular basis of organ fibrosis: potential therapeutic approaches.
AB  - Fibrosis, a non-physiological wound healing in multiple organs, is associated
      with end-stage pathological symptoms of a wide variety of vascular injury and
      inflammation related diseases. In response to chemical, immunological and
      physical insults, the body's defense system and matrix synthetic machinery
      respond to healing the wound and maintain tissue homeostasis. However,
      uncontrolled wound healing leads to scarring or fibrosis, a pathological
      condition characterized by excessive synthesis and accumulation of extracellular
      matrix proteins, loss of tissue homeostasis and organ failure. Understanding the
      actual cause of pathological wound healing and identification of igniter(s) of
      fibrogenesis would be helpful to design novel therapeutic approaches to control
      pathological wound healing and to prevent fibrosis related morbidity and
      mortality. In this article, we review the significance of a few key cytokines
      (TGF-beta, IFN-gamma, IL-10) transcriptional activators (Sp1, Egr-1, Smad3),
      repressors (Smad7, Fli-1, PPAR-gamma, p53, Klotho) and epigenetic modulators
      (acetyltransferase, methyltransferases, deacetylases, microRNAs) involved in
      major matrix protein collagen synthesis under pathological stage of wound
      healing, and the potentiality of these regulators as therapeutic targets for
      fibrosis treatment. The significance of endothelial to mesenchymal transition
      (EndMT) and senescence, two newly emerged fields in fibrosis research, has also
      been discussed.

PMID- 23856900
TI  - A long journey to effective obesity treatments: is there light at the end of the
      tunnel?
AB  - As the obesity epidemic continues, more Americans are getting fatter, having more
      weight-related problems such as cardiovascular disease, and are experiencing new
      metabolic dysfunctions. For over 50 years, the adipose tissue (AT), commonly
      referred to as fat, has been of interest to academic and clinical scientists,
      public health officials and individuals interested in body composition and image
      including much of the average public, athletes, parents, etc. On one hand,
      efforts to alter body shape, weight and body fat percentage still include bizarre
      and scientifically unfounded methods. On the other hand, significant new
      scientific strides have been made in understanding the growth, function and
      regulation of anatomical and systemic AT. Markers of transition/conversion of
      precursor cells that mature to form lipid assimilating adipocytes have been
      identified. Molecular 'master' regulators such as peroxisome proliferator
      activated receptor gamma and CCAAT-enhancer-binding proteins were uncovered and
      regulatory mechanisms behind variables of adiposity defined and refined.
      Interventions including pharmaceutical compounds, surgical, psychosocial
      interventions have also been tested. Has all of the preceding research helped
      alleviate the adverse physiologies of overweight and/or obese people? Does
      research to date point to new modalities that should be the focus of efforts to
      rid the world of obesity-related problems in the 21st century? This review
      provides a general overview of scientific efforts to date and a provocative view
      of the future for adiposity. 

PMID- 23856901
TI  - Weight control, endocrine hormones and cancer prevention.
AB  - The prevalence of obesity is increasing which becomes worrisome due to its
      association with several diseases and certain types of cancers. While weight
      control through dietary caloric restriction and/or physical activity protects
      against cancer in animal models, the underlying mechanisms are not fully defined.
      Weight loss due to negative energy balance is associated with alterations of
      multiple growth factors and endocrine hormones. The altered hormones and hormone
      related functions appear to be responsible for anti-cancer mechanisms. In this
      review, we summarize the recent studies related to weight loss and the altered
      endocrine hormones, focusing on the reduced levels of the mitogenic insulin-like
      growth factor 1 (IGF-1) and adipokine leptin as well as the raised levels of
      adiponectin and glucocorticoids. The potential molecular targets of these hormone
      dependent signalling pathways are also discussed. Considering the increasing
      trends of obesity throughout the world, a better understanding of the underlying
      mechanisms between body weight, endocrine hormones and cancer risk may lead to
      novel approaches to cancer prevention and treatment. 

PMID- 23856902
TI  - The proteomics and interactomics of human erythrocytes.
AB  - In this minireview, we focus on advances in our knowledge of the human
      erythrocyte proteome and interactome that have occurred since our seminal review
      on the topic published in 2007. As will be explained, the number of unique
      proteins has grown from 751 in 2007 to 2289 as of today. We describe how
      proteomics and interactomics tools have been used to probe critical protein
      changes in disorders impacting the blood. The primary example used is the work
      done on sickle cell disease where biomarkers of severity have been identified,
      protein changes in the erythrocyte membranes identified, pharmacoproteomic impact
      of hydroxyurea studied and interactomics used to identify erythrocyte protein
      changes that are predicted to have the greatest impact on protein interaction
      networks. 

PMID- 23856903
TI  - Oxidation and ubiquitination in neurodegeneration.
AB  - It is widely accepted that protein oxidation is involved in a variety of
      diseases, including neurodegenerative diseases. Especially during aging, a
      reduction in anti-oxidant defence mechanisms leads to an increased formation of
      free radical oxygen species and consequently results in a damage of proteins,
      including mitochondrial and synaptic ones. Even those proteins involved in repair
      and protein clearance via the ubiquitin proteasome and lysosomal system are
      subject to damage and show a reduced function. Here, we will discuss a variety of
      mechanisms and provide examples where cognition is affected and where repair
      mechanisms are no longer sufficient to compensate for a dysfunction of damaged
      proteins or even may become toxic. Next to physiological deficits, an
      accumulation of deficient proteins in aggresomes may occur and result in a
      formation of pathological hallmark structures typical for aging and disease. A
      major challenge is how to prevent aberrant oxidation, given that oxidation plays
      an essential role in aging and neurodegenerative diseases. Particularly
      interesting are the possibilities to reduce the formation of radical oxygen
      species leading to a dysfunction of protein repair and protein clearance, or to a
      formation of toxic byproducts accelerating neurodegeneration. 

PMID- 23856905
TI  - Follicle growth, ovulation, and luteal formation in primates and rodents: a
      comparative perspective.
AB  - Ovarian function has a great deal of functional overlap between species; antral
      follicles grow in response to FSH, ovulation involves proteolysis, and the
      steroidogenic pathway is largely the same. However, embedded in these
      similarities are important differences that reflect the evolutionary and natural
      history of species and may focus future research into these critical areas. This
      review compares ovarian function of rats and mice with primates, focusing on
      estradiol and follicle growth, steroidogenesis and rupture during the
      periovulatory interval, and the formation of a functional corpus luteum, drawing
      the conclusion that careful comparison of species yields more functional
      information about both than studying them in isolation. 

PMID- 23856904
TI  - Role of p62/SQSTM1 in liver physiology and pathogenesis.
AB  - p62/sequestosome-1/A170/ZIP (hereafter referred to as p62) is a scaffold protein
      that has multiple functions, such as signal transduction, cell proliferation,
      cell survival, cell death, inflammation, tumourigenesis and oxidative stress
      response. While p62 is an autophagy substrate and is degraded by autophagy, p62
      serves as an autophagy receptor for selective autophagic clearance of protein
      aggregates and organelles. Moreover, p62 functions as a signalling hub for
      various signalling pathways, including NF-kappaB, Nrf2 and mTOR. In this review,
      we discuss the pathophysiological role of p62 in the liver, including formation
      of hepatic inclusion bodies, cholestasis, obesity, insulin resistance, liver cell
      death and tumourigenesis.

PMID- 23856907
TI  - Challenges for the formulation of a universal vaccine against dengue.
AB  - Dengue is rapidly becoming a disease of an escalating global public health
      concern. The disease is a vector-borne disease, transmitted by the bite of an
      Aedes spp. mosquito. Dynamic clinical manifestations, ranging from asymptomatic,
      flu-like febrile illness, dengue fever (DF) to dengue hemorrhagic fever (DHF)
      with or without dengue shock syndrome (DSS), make the disease one of the most
      challenging to diagnose and treat. DF is a self-limited illness, while DHF/DSS,
      characterized by plasma leakage resulting from an increased vascular
      permeability, can have severe consequences, including death. The pathogenesis of
      dengue virus infection remains poorly understood, mainly due to the lack of a
      suitable animal model that can recapitulate the cardinal features of human dengue
      diseases. Currently, there is no specific treatment or antiviral therapy
      available for dengue virus infection and supportive care with vigilant monitoring
      is the principle course of treatment. Since vector control programs have been
      largely unsuccessful in preventing outbreaks, vaccination seems to be the most
      viable option for prevention. There are four dengue viral serotypes and each one
      of them is capable of causing severe dengue. Although immunity induced by
      infection by one serotype is effective in protection against the homologous viral
      serotype, it only has a transient protective effect against infection with the
      other three serotypes. The meager cross protective immunity generated wanes over
      time and may even induce a harmful effect at the time of subsequent secondary
      infection. Thus, it is imperative to have a vaccine that can elicit equal and
      long-lasting immunity to all four serotypes simultaneously. Numerous tetravalent
      vaccines are currently either in the pipeline for clinical trials or under
      development. For those frontrunner tetravalent vaccines in clinical trials,
      despite good safety and immunogenicity profiles registered, issues such as
      imbalanced immune responses between serotypes and questions with regard to
      whether the optimum formulation have been identified remain unresolved. This
      review centers on these issues and offers strategies that may improve the
      tetravalent vaccine formulation. 

PMID- 23856906
TI  - Recent advances in the morphological and functional heterogeneity of the biliary
      epithelium.
AB  - This review focuses on the recent advances related to the heterogeneity of
      different-sized bile ducts with regard to the morphological and phenotypical
      characteristics, and the differential secretory, apoptotic and proliferative
      responses of small and large cholangiocytes to gastrointestinal
      hormones/peptides, neuropeptides and toxins. We describe several in vivo and in
      vitro models used for evaluating biliary heterogeneity. Subsequently, we discuss
      the heterogeneous proliferative and apoptotic responses of small and large
      cholangiocytes to liver injury and the mechanisms regulating the differentiation
      of small into large (more differentiated) cholangiocytes. Following a discussion
      on the heterogeneity of stem/progenitor cells in the biliary epithelium, we
      outline the heterogeneity of bile ducts in human cholangiopathies. After a
      summary section, we discuss the future perspectives that will further advance the
      field of the functional heterogeneity of the biliary epithelium.

PMID- 23856908
TI  - Targeting the opioid growth factor: opioid growth factor receptor axis for
      treatment of human ovarian cancer.
AB  - The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is a
      biological pathway that is present in human ovarian cancer cells and tissues.
      OGF, chemically termed [Met(5)]-enkephalin, is an endogenous opioid peptide that
      interfaces with OGFr to delay cells moving through the cell cycle by upregulation
      of cyclin-dependent inhibitory kinase pathways. OGF inhibitory activity is dose
      dependent, receptor mediated, reversible, protein and RNA dependent, but not
      related to apoptosis or necrosis. The OGF-OGFr axis can be targeted for treatment
      of human ovarian cancer by (i) administration of exogenous OGF, (ii) genetic
      manipulation to over-express OGFr and (iii) use of low dosages of naltrexone, an
      opioid antagonist, which stimulates production of OGF and OGFr for subsequent
      interaction following blockade of the receptor. The OGF-OGFr axis may be a
      feasible target for treatment of cancer of the ovary (i) in a prophylactic
      fashion, (ii) following cytoreduction or (iii) in conjunction with standard
      chemotherapy for additive effectiveness. In summary, preclinical data support the
      transition of these novel therapies for treatment of human ovarian cancer from
      the bench to bedside to provide additional targets for treatment of this
      devastating disease.

PMID- 23856912
TI  - The SoundBite hearing system: patient-assessed safety and benefit study.
AB  - OBJECTIVES/HYPOTHESIS: To determine the safety and efficacy of the SoundBite for
      patients over a 6 month period of use. STUDY DESIGN: Prospective, multisite,
      nonrandomized patient enrollment with outcomes based on audiometric profile and
      self-reported assessment. METHODS: Patients with single-sided deafness were
      eligible for the study. Patients were fit with the standard SoundBite sound
      transducer and were asked to wear the device regularly for 6 months. At the end
      of the trial period, patients completed both a self-assessment and the
      Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaires. RESULTS:
      Thirty-four subjects completed the study. Mean APHAB scores improved
      significantly for ease of communication (P < 0.001), background noise (P <
      0.001), reverberation (P < 0.001), and global benefit (P < 0.001). Patients
      reported high rates of auditory benefit in a variety of listening situations and
      high rates of overall satisfaction with the device. One adverse event with a
      superficial mouth sore was reported and resolved after appropriate dental care.
      Twelve patients (35%) reported acoustic feedback. In six of these patients, the
      feedback resolved after device adjustment. CONCLUSION: The SoundBite is a new
      hearing prosthesis that delivers bone conduction energy. It offers advantages
      over traditional osseointegrated devices that require surgical placement. Patient
      satisfaction with the device after 6 months of regular use is high. The SoundBite
      provided improvement in ease of communication, hearing in background noise, sound
      reverberation, and an overall global hearing benefit. Acoustic feedback is the
      most commonly reported problem with the SoundBite, and this is minimized with
      proper fitting.

PMID- 23856913
TI  - Application of capillary electrophoretic chips in protein profiling of plant
      extracts for identification of genetic modifications of maize.
AB  - In this study, the chip gel electrophoresis with LIF detection was applied in
      protein profiling of fractionated and total extracts of maize standards. The
      sensitivity of such determinations can be enhanced by lyophilization of extracts
      or employing filtering and preconcentration with cutoff filters. Combinatorial
      peptide ligand library applied for sample processing prior to the electrophoretic
      analysis was, especially, an effective pretreatment step in the determination of
      low-abundance proteins. Several repeatable differences were observed for protein
      profiles between maize standards not containing the genetically modified
      organisms (GMOs) and those containing GMO, which can be potentially employed for
      identification of GMO in maize samples and foods of maize origin. 

PMID- 23856911
TI  - Recent progress in pancreatic cancer.
AB  - Pancreatic cancer is currently one of the deadliest of the solid malignancies.
      However, surgery to resect neoplasms of the pancreas is safer and less invasive
      than ever, novel drug combinations have been shown to improve survival, advances
      in radiation therapy have resulted in less toxicity, and enormous strides have
      been made in the understanding of the fundamental genetics of pancreatic cancer.
      These advances provide hope but they also increase the complexity of caring for
      patients. It is clear that multidisciplinary care that provides comprehensive and
      coordinated evaluation and treatment is the most effective way to manage patients
      with pancreatic cancer.

PMID- 23856914
TI  - Antisense technology: an emerging platform for cardiovascular disease
      therapeutics.
AB  - Antisense oligonucleotides and small interfering RNAs, which suppress the
      translation of specific mRNA target proteins, are emerging as important
      therapeutic modalities for the treatment of cardiovascular disease. Over the last
      25 years, the advances in all aspects of antisense technology, as well as a
      detailed understanding of the mechanism of action of antisense drugs, have
      enabled their use as therapeutic agents. These advancements culminated in the FDA
      approval of the first chronically administered cardiovascular antisense
      therapeutic, mipomersen, which targets hepatic apolipoprotein B mRNA. This review
      provides a brief history of antisense technology, highlights the progression of
      mipomersen from preclinical studies to multiple Phase III registration trials,
      and gives an update on the status of other cardiovascular antisense therapeutics
      currently in the clinic. 

PMID- 23856915
TI  - Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 1:
      feature extraction.
AB  - This is the first part of a two-part paper on the application of computer-aided
      diagnosis to diffuse optical tomography (DOT). An approach for extracting
      heuristic features from DOT images and a method for using these features to
      diagnose rheumatoid arthritis (RA) are presented. Feature extraction is the focus
      of Part 1, while the utility of five classification algorithms is evaluated in
      Part 2. The framework is validated on a set of 219 DOT images of proximal
      interphalangeal (PIP) joints. Overall, 594 features are extracted from the
      absorption and scattering images of each joint. Three major findings are deduced.
      First, DOT images of subjects with RA are statistically different (p<0.05) from
      images of subjects without RA for over 90% of the features investigated. Second,
      DOT images of subjects with RA that do not have detectable effusion, erosion, or
      synovitis (as determined by MRI and ultrasound) are statistically
      indistinguishable from DOT images of subjects with RA that do exhibit effusion,
      erosion, or synovitis. Thus, this subset of subjects may be diagnosed with RA
      from DOT images while they would go undetected by reviews of MRI or ultrasound
      images. Third, scattering coefficient images yield better one-dimensional
      classifiers. A total of three features yield a Youden index greater than 0.8.
      These findings suggest that DOT may be capable of distinguishing between PIP
      joints that are healthy and those affected by RA with or without effusion,
      erosion, or synovitis.

PMID- 23856916
TI  - Computer-aided diagnosis of rheumatoid arthritis with optical tomography, Part 2:
      image classification.
AB  - This is the second part of a two-part paper on the application of computer-aided
      diagnosis to diffuse optical tomography (DOT) for diagnosing rheumatoid arthritis
      (RA). A comprehensive analysis of techniques for the classification of DOT images
      of proximal interphalangeal joints of subjects with and without RA is presented.
      A method for extracting heuristic features from DOT images was presented in Part
      1. The ability of five classification algorithms to accurately label each DOT
      image as belonging to a subject with or without RA is analyzed here. The
      algorithms of interest are the k-nearest-neighbors, linear and quadratic
      discriminant analysis, self-organizing maps, and support vector machines (SVM).
      With a polynomial SVM classifier, we achieve 100.0% sensitivity and 97.8%
      specificity. Lower bounds for these results (at 95.0% confidence level) are 96.4%
      and 93.8%, respectively. Image features most predictive of RA are from the
      spatial variation of optical properties and the absolute range in feature values.
      The optimal classifiers are low-dimensional combinations (<7 features). These
      results underscore the high potential for DOT to become a clinically useful
      diagnostic tool and warrant larger prospective clinical trials to conclusively
      demonstrate the ultimate clinical utility of this approach.

PMID- 23856917
TI  - Interventions to mitigate emergency department and hospital crowding during an
      infectious respiratory disease outbreak: results from an expert panel.
AB  - OBJECTIVE: To identify and prioritize potential Emergency Department (ED) and
      hospital-based interventions which could mitigate the impact of crowding during
      patient surge from a widespread infectious respiratory disease outbreak and
      determine potential data sources that may be useful for triggering decisions to
      implement these high priority interventions. DESIGN: Expert panel utilizing
      Nominal Group Technique to identify and prioritize interventions, and in
      addition, determine appropriate "triggers" for implementation of the high
      priority interventions in the context of four different infectious respiratory
      disease scenarios that vary by patient volumes (high versus low) and illness
      severity (high versus low). SETTING: One day in-person conference held November,
      2011. PARTICIPANTS: Regional and national experts representing the fields of
      public health, disease surveillance, clinical medicine, ED operations, and
      hospital operations. MAIN OUTCOME MEASURE: Prioritized list of potential
      interventions to reduce ED and hospital crowding, respectively. In addition, we
      created a prioritized list of potential data sources which could be useful to
      trigger interventions. RESULTS: High priority interventions to mitigate ED surge
      included standardizing admission and discharge criteria and instituting infection
      control measures. To mitigate hospital crowding, panelists prioritized mandatory
      vaccination and an algorithm for antiviral use. Data sources identified for
      triggering implementation of these interventions were most commonly ED and
      hospital utilization metrics. CONCLUSIONS: We developed a prioritized list of
      potentially useful interventions to mitigate ED and hospital crowding in various
      outbreak scenarios. The data sources identified to "trigger" the implementation
      of these high priority interventions consist mainly of sources available at the
      local, institutional level.

PMID- 23856918
TI  - Serum S100B protein is increased and correlates with interleukin 6, hypoperfusion
      indices, and outcome in patients admitted for surgical control of hemorrhage.
AB  - S100B protein, an acknowledged biomarker of brain injury, has been reported to be
      increased in hemorrhagic shock. Also, acute hemorrhage is associated with
      inflammatory response. The aim of this study was to investigate the
      concentrations of serum S100B and the potential relationships with interleukin 6
      (IL-6), severity of tissue hypoperfusion, and prognosis in patients admitted for
      surgical control of severe hemorrhage. Patients undergoing elective abdominal
      aortic aneurysm surgery participated as control subjects. Serum samples were
      drawn before, at the end of surgery, and after 6 and 24 h. Sixty-four patients
      with severe hemorrhage (23 trauma and 41 nontrauma) and 17 control subjects were
      included. Increased preoperative concentrations of S100B protein (1.70 +/- 2.13
      and 0.81 +/- 1.23 MUg/L) and IL-6 (241 +/- 291 and 226 +/- 238 pg/mL) were found
      in patients with traumatic and nontraumatic reason, respectively, and remained
      elevated throughout 24 h. Compared with nontrauma, trauma patients exhibited
      higher preoperative S100B levels (P < 0.05). Overall mortality was 47%. In
      control subjects, preoperative S100B and IL-6 levels were within normal limits
      and increased at the end of surgery (P < 0.001 and P < 0.01, respectively).
      Preoperative S100B correlated with IL-6 (r = 0.78, P < 0.01), arterial lactate (r
      = 0.50, P < 0.01), pH (r = -0.45, P < 0.01), and bicarbonate (r = -0.40, P <
      0.01). Multiple analysis revealed that preoperative S100B in trauma and lactate
      in nontrauma patients were independently associated with outcome. In predicting
      death, preoperative S100B yielded receiver operator characteristics curve areas
      of 0.75 for all patients and 0.86 for those with trauma. These results indicate
      that severe hemorrhage in patients without brain injury is associated with
      increased serum levels of S100B, which correlates with IL-6 and tissue
      hypoperfusion. Moreover, the predictive ability of S100B for mortality, suggests
      that it could be a marker of potential clinical value in identifying, among
      patients with severe hemorrhage, those at greater risk for adverse outcome. 

PMID- 23856919
TI  - Role of interleukin 1 receptor like 1 (ST2) in gram-negative and gram-positive
      sepsis in mice.
AB  - BACKGROUND: Interleukin 1 receptor-like 1 (ST2) has been implicated as a negative
      regulator of Toll-like receptor signaling. We here sought to elucidate the role
      of ST2 in cytokine release and systemic infection caused by two common human
      sepsis pathogens, Streptococcus pneumoniae (gram-positive) and Klebsiella
      pneumoniae (gram-negative). METHODS: Whole blood leukocytes and splenocytes were
      harvested from ST2-deficient (st2) and wild-type (WT) mice and stimulated ex vivo
      with S. pneumoniae or K. pneumoniae. In addition, st2 and WT mice were infected
      intravenously with these bacteria, and bacterial loads and cytokine levels were
      measured in blood, spleens and lungs at 6, 24, and 48 h thereafter. RESULTS:
      Unexpectedly, st2 blood leukocytes and splenocytes produced lower levels of
      cytokines and chemokines than WT cells in response to either pathogen. In
      contrast, the in vivo role of ST2 during sepsis caused by these bacteria was
      limited, although at 6 and 24 h after infection with S. pneumoniae bacterial
      loads were lower in spleens of st2 mice. CONCLUSIONS: ST2 augments rather than
      inhibits cytokine release by blood leukocytes and splenocytes exposed to S.
      pneumoniae or K. pneumoniae, but plays a limited role in host defense during
      sepsis caused by these pathogens.

PMID- 23856920
TI  - High-dose acetylsalicylic acid is superior to low-dose as well as to clopidogrel
      in preventing lipopolysaccharide-induced lung injury in mice.
AB  - BACKGROUND: Use of aspirin (acetylsalicylic acid [ASA]) was found to improve
      outcome in animal models of acute lung injury (ALI) or its more severe form,
      acute respiratory distress syndrome. In patients with acute respiratory distress
      syndrome, data indicating a protective effect of ASA are less convincing. We
      hypothesize that ASA in a high dose is superior to low-dose ASA in preventing
      lung injury. Also, the effect on lung injury of inhibiting platelet activation by
      clopidogrel was investigated. METHODS: Acute lung injury was induced by
      intranasal instillation of 10 MUg lipopolysaccharide (LPS). Before LPS, BALB/c
      mice were pretreated with either high dose of ASA (100 MUg/g intraperitoneally,
      low-dose ASA (12.5 MUg/g i.p), clopidogrel (50 MUg/g i.p), or clopidogrel in
      combination with low dose of ASA. Controls received vehicle or LPS without
      intervention. Five hours after LPS, bronchoalveolar lavage fluid (BALF) and
      plasma were obtained. MEASUREMENTS AND MAIN RESULTS: All treatment regimens
      reduced neutrophil influx in the BALF compared with LPS controls (high-dose ASA
      75% +/- 2% [mean +/- SD], low-dose ASA 86% +/- 3%, clopidogrel 82% +/- 1%, and
      low-dose ASA-clopidogrel 82% +/- 3% vs. LPS control 88% +/- 2%; P <= 0.05). High
      dose ASA reduced BALF levels of protein compared with LPS controls (median
      [interquartile range], 0.2 [15] vs. 75 [20] pg/mL; P < 0.01), to a greater extent
      than after low-dose ASA (48 [32] pg/mL), clopidogrel (37 [23] pg/mL), or low-dose
      ASA-clopidogrel (57 [8] pg/mL). CONCLUSIONS: High-dose ASA is superior to low
      dose ASA, clopidogrel, and to a combination of clopidogrel and low-dose ASA in
      attenuating LPS-induced lung injury in mice, suggesting high-dose ASA to be the
      antiplatelet therapy of choice in further research on preventing ALI.

PMID- 23856921
TI  - Combined hemorrhage/trauma models in pigs-current state and future perspectives.
AB  - The majority of injury combinations in multiply injured patients entail the
      chest, abdomen, and extremities. Numerous pig models focus on the investigation
      of posttraumatic pathophysiology, organ performance monitoring and on potential
      treatment options. Depending on the experimental question, previous authors have
      included isolated insults (controlled or uncontrolled hemorrhage, chest trauma)
      or a combination of these injuries (hemorrhage with abdominal trauma, chest
      trauma, traumatic brain injury, and/or long-bone fractures). Combined trauma
      models in pigs can provide a high level of clinical relevance, when they are
      properly designed and mimicking the clinical situation. Most of these models
      focus on the first hours after trauma, to assess the acute sequel of traumatic
      hemorrhage. However, hemorrhagic shock and the associated mass transfusion are
      also major causes for organ failure and mortality in the later clinical course.
      Thus, most models lack information on the pathomechanisms during the late
      posttraumatic phase. Studying new therapies only during the early phase is also
      not reflective of the clinical situation. Therefore, a longer observation period
      is required to study the effects of therapeutic approaches during intensive care
      treatment when using animal models. These long-term studies of combined trauma
      models will allow the development of valuable therapeutic approaches relevant for
      the later posttraumatic course. This review summarizes the existing porcine
      models and outlines the need for long-term models to provide real effective novel
      therapeutics for multiply injured patients to improve organ function and clinical
      outcome. 

PMID- 23856922
TI  - Panax quinquefolium saponin attenuates ventricular remodeling after acute
      myocardial infarction by inhibiting chop-mediated apoptosis.
AB  - Panax quinquefolium saponin (PQS) alleviates hypoxia-reoxygenation injury of
      cardiomyocytes in vitro by inhibiting excessive endoplasmic reticulum stress
      (ERS)-related apoptosis. We hypothesized that inhibition of excessive ERS-related
      apoptosis contributes to cardioprotection in ventricular remodeling after acute
      myocardial infarction (AMI). Sprague-Dawley rats subjected to AMI were randomly
      treated with water, PQS (50 mg/kg per day, 100 mg/kg per day, or 200 mg/kg per
      day), or taurine (300 mg/kg per day), an ERS inhibitor, for 4 weeks. Left
      ventricular (LV) fractional shortening, ejection fraction, and structure were
      then evaluated using echocardiography. Myocardial infarct size was measured by
      Evans blue and 2,3,5-triphenyhetrazolium chloride staining. The hydroxyproline
      level was assayed using the colorimetric method. Cardiomyocyte apoptosis was
      detected using terminal deoxynucleotidyl transferase-mediated dUTP biotin nick
      end labeling. In addition, expression of ERS molecules in the noninfarcted
      myocardium was detected using Western blotting. We found that PQS treatment
      significantly reduced infarct size and LV dilation and improved LV ejection
      fraction and fractional shortening in rat hearts. Panax quinquefolium saponin
      treatment also decreased hydroxyproline level in noninfarcted myocardium. Panax
      quinquefolium saponin treatment significantly decreased expression of glucose
      regulating protein 78, calreticulin, C/EBP homologous protein (CHOP), and Bax
      protein, as well as increased Bcl-2 protein expression in noninfarcted
      myocardium. Panax quinquefolium saponin treatment (200 mg/kg per day) mimicked
      the results achieved from the taurine-treated rats. Expression of CHOP positively
      correlated with the apoptosis index of cardiomyocytes in the noninfarcted
      myocardium (r = 0.797, P < 0.01). Taken together, PQS treatment significantly
      improves AMI-induced LV remodeling, and this may be attributed to inhibiting CHOP
      mediated ERS-related apoptosis. 

PMID- 23856923
TI  - Low-dose vasopressin improves cardiac function in newborn piglets with acute
      hypoxia-reoxygenation.
AB  - Cardiovascular dysfunction in asphyxiated neonates contributes significantly to
      their morbidity and mortality. We have recently shown that a low-dose vasopressin
      infusion (0.005 - 0.01 units/kg per hour) may improve myocardial oxygen transport
      balance in a swine model of neonatal hypoxia-reoxygenation. We aimed to compare
      the systemic and regional hemodynamic effects of low-dose vasopressin to
      dobutamine, a synthetic beta-adrenoreceptor agonist. Piglets (1 - 5 days old, 1.6
      - 2.2 kg) were anesthetized and instrumented to continuously monitor systemic
      hemodynamic parameters, including cardiac output and mesenteric flow indices.
      After 2 h of hypoxia (10% - 15% O2), piglets had normoxic reoxygenation for 4 h.
      In a blinded randomized fashion, piglets received infusion of either vasopressin
      (0.01 units/kg per hour started at 30 min of reoxygenation) or dobutamine (20
      MUg/kg per minute started at 2 h of reoxygenation) (n = 8 per group). Hypoxia
      reoxygenation controls (placebo, n = 8) and sham-operated (n = 5) piglets were
      also studied. Tissue lactate, glutathione, glutathione disulfide, and lipid
      hydroperoxides levels and histology of the left ventricle and the small bowel
      were analyzed. Plasma was also analyzed for troponin-I and intestinal fatty acid
      binding protein levels. Piglets subjected to hypoxia-reoxygenation had
      cardiogenic shock and metabolic acidosis, which improved on reoxygenation. During
      recovery, cardiac output and mesenteric flows gradually deteriorated and were
      increased similarly in vasopressin- and dobutamine-treated piglets (P < 0.05 vs.
      controls). Plasma troponin-I and left ventricular lactate levels were lower in
      the vasopressin and dobutamine groups (P < 0.05 vs. controls), with no difference
      in the histological analysis among groups. The intestinal GSSG/GSH ratio and
      lipid hydroperoxides level were lower in the vasopressin and dobutamine groups (P
      < 0.05 vs. controls). This study is the first to demonstrate that a low-dose
      vasopressin infusion used in the setting of neonatal swine model of hypoxia
      reoxygenation is associated with an improvement in cardiac output and mesenteric
      perfusion. 

PMID- 23856924
TI  - G-CSF enhances resolution of Staphylococcus aureus wound infection in an age
      dependent manner.
AB  - This study tested the hypothesis that heightened bacterial colonization and
      delayed wound closure in aged mice could be attenuated by granulocyte colony
      stimulating factor (G-CSF) treatment. Previously, we reported that aged mice had
      elevated bacterial levels, protracted wound closure, and reduced wound neutrophil
      accumulation after Staphylococcus aureus wound infection relative to young mice.
      In aseptic wound models, G-CSF treatment improved wound closure in aged mice to
      rates observed in young mice. Given these data, our objective was to determine if
      G-CSF could restore age-associated differences in wound bacterial burden and
      closure by increasing wound neutrophil recruitment. Young (3- to 4-month) and
      aged (18- to 20-month) BALB/c mice received three dorsal subcutaneous injections
      of G-CSF (250 ng/50 MUL per injection) or saline control (50 MUL per injection)
      30 min after wound infection. Mice were killed at days 3 and 7 after wound
      infection, and bacterial colonization, wound size, wound leukocyte accumulation,
      and peripheral blood were evaluated. At days 3 and 7 after wound infection,
      bacterial colonization was significantly reduced in G-CSF-treated aged mice to
      levels observed in saline-treated young animals. Wound size was reduced in G-CSF
      treated aged animals, with no effect on wound size in G-CSF-treated young mice.
      Local G-CSF treatment significantly enhanced neutrophil wound accumulation in
      aged mice, whereas there was no G-CSF-induced change in young mice. These data
      demonstrate that G-CSF enhances bacterial clearance and wound closure in an age
      dependent manner. Moreover, G-CSF may be of therapeutic potential in the setting
      of postoperative wound infection or chronic nonhealing wounds in elderly
      patients. 

PMID- 23856928
TI  - First International Symposium "Epigenetic Control of Skin Development and
      Regeneration": how chromatin regulators orchestrate skin functions.

PMID- 23856929
TI  - Photosensitizing agents and the risk of non-melanoma skin cancer: a population
      based case-control study.
AB  - Robinson et al. report a population-based case-control study to examine the
      association between a history of photosensitizing medication use and non-melanoma
      skin cancer. They report an increased risk of basal cell carcinoma with
      tetracycline use and of squamous cell carcinoma with diuretic use. Appropriate
      counseling regarding sun exposure may reduce skin cancer in patients exposed to
      these medications. 

PMID- 23856930
TI  - Phacomatosis pigmentokeratotica is a "pseudodidymosis".
AB  - In phacomatosis pigmentokeratotica, papular nevus spilus coexists with nevus
      sebaceus. The disorder was thought to be a didymosis with early postzygotic
      recombination. In this issue, however, Groesser and co-workers provide a new
      concept. Both nevi originate from a single heterozygous HRAS mutation in a
      pluripotent progenitor cell. This new understanding has implications for other
      proposed examples of didymosis in humans. 

PMID- 23856931
TI  - Innate immunity stimulates permeability barrier homeostasis.
AB  - A key function of the skin is to provide a permeability barrier to restrict the
      movement of water, electrolytes, and other small molecules between the outside
      environment and the internal milieu. Following disruption of the permeability
      barrier, there is a rapid restoration of barrier function, and one of the key
      signals initiating this repair response is a decrease in the concentration of
      calcium in the outer epidermis. In this issue, Borkowski et al. present evidence
      showing that activation of Toll receptor 3 by double-stranded RNA may be another
      pathway for activation of permeability barrier repair. These results provide
      further evidence for a link between innate immunity and the permeability barrier.

PMID- 23856932
TI  - A STATement on vemurafenib-resistant melanoma.
AB  - Despite recent advancements in the treatment of late-stage mutant BRAF (V600E/K)
      melanomas, a major hurdle continues to be acquired resistance to BRAF inhibitors
      such as vemurafenib. The mechanisms for resistance have proven to be
      heterogeneous, emphasizing the need to use broad therapeutic approaches. In this
      issue, the study "Stat3-targeted therapies overcome the acquired resistance to
      vemurafenib in melanomas" by Liu et al. proposes that signal transducer and
      activator of transcription 3 (STAT3)-paired box 3 (PAX3) signaling may be a
      mechanism that is used by melanomas to resist RAF inhibitors. 

PMID- 23856933
TI  - Clinical Implications of CD8+ T-cell infiltration in frequent and rare cancers.
AB  - Recent studies of cancer patients revealed high diversity in oncogenic
      mechanisms, leading to increased treatment individualization for subgroups of
      patients with frequent cancers. A similar development may not be possible for
      patients with rare cancers, such as Merkel cell carcinoma (MCC). Finding shared
      disease mechanisms may open new options to understanding and treating such
      tumors. Tumor-infiltrating CD8+ T cells are frequently associated with favorable
      clinical outcome in a remarkably large spectrum of cancers. In this issue,
      Afanasiev et al. suggest a mechanism that may hinder the tumor homing of CD8+ T
      cells in MCC patients. It is possible that therapeutic mobilization of anti
      cancer T cells may be useful in patients who share this specific immune
      biological feature. 

PMID- 23856935
TI  - Next-generation sequencing: methodology and application.

PMID- 23856936
TI  - JID VisualDx Quiz: August 2013.

PMID- 23856934
TI  - Resveratrol stimulates sphingosine-1-phosphate signaling of cathelicidin
      production.
AB  - We recently discovered a regulatory mechanism that stimulates the production of
      the multifunctional antimicrobial peptide cathelicidin antimicrobial peptide
      (CAMP). In response to subtoxic levels of ER stress, increased sphingosine-1
      phosphate (S1P) production activates an NFkappaB?C/EBPalpha-dependent pathway
      that enhances CAMP production in cultured human keratinocytes. As the
      multifunctional stilbenoid compound resveratrol (RESV) increases ceramide (Cer)
      levels, a precursor of S1P, we hypothesized and assessed whether RESV could
      exploit the same pathway to regulate CAMP production. Accordingly, RESV
      significantly increased Cer and S1P levels in cultured keratinocytes, paralleled
      by increased CAMP mRNA/protein expression. Furthermore, topical RESV also
      increased murine CAMP mRNA/protein expression in mouse skin. Conversely, blockade
      of Cer-->sphingosine-->S1P metabolic conversion, with specific inhibitors of
      ceramidase or sphingosine kinase, attenuated the expected RESV-mediated increase
      in CAMP expression. The RESV-induced increase in CAMP expression required both NF
      kappaB and C/EBPalpha transactivation. Moreover, conditioned media from
      keratinocytes treated with RESV significantly suppressed Staphylococcus aureus
      growth. Finally, topical RESV, if not coapplied with a specific inhibitor of
      sphingosine kinase, blocked S. aureus invasion into murine skin. These results
      demonstrate that the dietary stilbenoid RESV stimulates S1P signaling of CAMP
      production through an NF-kappaB-->C/EBPalpha-dependent mechanism, leading to
      enhanced antimicrobial defense against exogenous microbial pathogens.

PMID- 23856937
TI  - Sham-controlled implantation after preimplantation genetic screening by polar
      body biopsy and FISH.
AB  - PURPOSE: Preimplantation genetic screening wants to improve artificial
      reproductive technologies, primarily by raising the rates of pregnancy,
      implantation and birth. We investigated if embryos derived from oocytes detected
      euploid for five chromosomes implant better than those which were biopsied but
      where the genetic detection failed. They were nevertheless transferred, thus
      serving as a sham control. METHOD: From 2004 to 2008 we performed 104 cycles of
      PGS with laser biopsy of the first polar body and FISH with five chromosomes. It
      was offered to all patients with eight or more oocytes, free of charge. The
      average female age was 36 years. If no euploid oocytes were available, not
      detected oocytes were transferred. RESULT: In 104 cycles 99 embryo transfers (95
      %) were performed, resulting in 28 pregnancies (27 %), 20 births (71 %) and 8
      miscarriages (29 %). The implantation rate in the euploid group was 19 vs. 13 %
      in the not detected group (n.s.). This trend was the same independent of age and
      embryo morphology. CONCLUSION: The pregnancy rate does not differ significantly
      from the national average. The trend in better implantation rates of euploid
      oocytes justifies a continuation of studies in this matter.

PMID- 23856938
TI  - Expression of membrane drug efflux transporters in the sigmoid colon of HIV
      infected and uninfected men.
AB  - The use of antiretroviral therapy (ART) as pre-exposure prophylaxis (PrEP) has
      gained global attention as a promising HIV prevention strategy in men who have
      sex with men. Permeability of these agents in the rectal mucosa may be partially
      regulated by interactions with drug efflux transporters, P-glycoprotein (P-gp),
      multidrug resistance-associated proteins (MRPs) and/or breast cancer resistance
      protein (BCRP). The objective of this work was to investigate the expression of
      drug efflux transporters in recto-sigmoid colon tissues of HIV-infected and
      uninfected men, and evaluate the association of ART and/or HIV infection with
      drug transporter expression. MDR1/P-gp, MRPs (1-4) and BCRP mRNA and protein
      expression were detected in sigmoid colon biopsies of HIV-uninfected individuals.
      Biopsies from HIV-infected, ART-naive participants revealed a significant
      downregulation of P-gp and MRP2 protein levels compared to HIV-uninfected
      individuals. Biopsies from HIV-infected ART-treated patients showed 1.9-fold
      higher P-gp protein expression and 1.5-fold higher MRP2 protein expression
      compared to the ones obtained from the HIV-infected ART-naive patients. This is a
      first report demonstrating that HIV infection or ART could alter expression of
      drug efflux transporters in gut mucosa which in turn could affect the
      permeability of PrEP antiretroviral agents across this barrier, a highly
      vulnerable site of HIV transmission. 

PMID- 23856939
TI  - Comparison of alpha2-macroglobulin synthesis by juvenile vs. mature rats after
      identical inflammatory stimulation.
AB  - Synthesis of alpha2-macoglobulin (alpha2M) by 3-week-old juvenile rats was
      compared to that of mature 7- and 11-week-old rats. Serum concentrations of
      alpha2M, interleukin (IL)-6- and cytokine-induced neutrophil chemoattractant
      (CINC)-1 were measured by enzyme-linked immunosorbent assay. The area under the
      concentration vs. time curve (AUC) for alpha2M was significantly different among
      the three groups. The synthesis of alpha2M increased in an age-dependent manner.
      No significant difference was observed for the AUC of IL-6, but that of CINC-1 in
      3-week-old rats was significantly lower than that in 7- or 11-week-old rats.
      These results suggest that synthesis of alpha2M was increased in mature compared
      to juvenile rats, possibly due to differences in liver function. The maximum
      concentration of CINC-1 in 3-week-old rats was observed 6 h after turpentine oil
      injection. The serum concentrations of IL-6 and CINC-1 increased more quickly in
      juvenile rats than in mature rats after inflammatory stimulation.

PMID- 23856941
TI  - [Investigation of the influence of environmental factors in severe psychiatric
      diseases: epigenetics as new research tool].

PMID- 23856940
TI  - IRAK1-dependent signaling mediates mortality in polymicrobial sepsis.
AB  - Interleukin-1 receptor-associated kinase (IRAK1) is a key regulatory protein in
      TLR/IL1R-mediated cell activation during inflammatory response. Studies indicated
      that pending on the nature of the used inflammatory model, downregulation of
      IRAK1 may be beneficial or detrimental. However, the role of IRAK1 in affecting
      outcome in polymicrobial sepsis is unknown. We tested this question using an
      IRAK1-deficient mouse strain and cecal ligation and puncture (CLP) procedure,
      which is a clinically relevant rodent septic model. Sepsis-induced mortality was
      markedly lower in IRAK1-deficient mice (35 %) compared to WT (85 %). Sepsis
      induced increases in blood IL-6 and IL-10 levels were blunted at 6 h post-CLP in
      IRAK1 deficiency compared to WT, but cytokine levels were similar at 20 h post
      CLP. Sepsis-induced blood granulocytosis and depletion of splenic B cells were
      also blunted in IRAK1-deficient mice as compared to WT. Analysis of TLR-mediated
      cytokine responses by IRAK1-deficient and WT macrophages ex vivo indicated a TLR4
      dependent downregulation of IL-6 and IL1beta in IRAK1 deficiency, whereas TLR2
      dependent responses were unaffected. TLR7/8-mediated IL-6, IL1beta, and IL-10
      production was also blunted in IRAK1 macrophages as compared to WT. The study
      shows that IRAK1 deficiency impacts multiple TLR-dependent pathways and decreases
      early cytokine responses following polymicrobial sepsis. The delayed inflammatory
      response caused by the lack of IRAK1 expression is beneficial, as it manifests a
      marked increased chance of survival after polymicrobial sepsis.

PMID- 23856943
TI  - [Standardised psychopathological rating scales for the diagnosis of ADHD in
      adults].
AB  - Ascertaining the diagnosis of ADHD in adults according to DSM-IV requires
      determination of the presence of symptoms of inattention, hyperactivity and
      impulsivity during both childhood and adulthood. Developmental changes of
      psychopathology, age-related comorbidity and functional and psychosocial problems
      associated with ADHD have to be taken into account during the diagnostic process.
      The use of standardised instruments might improve validity and reliability of the
      diagnosis. These diagnostic tools comprise self and expert ratings as well as
      observer ratings for the retrospective assessment of childhood and the evaluation
      of current ADHD symptoms. Here we give an overview of the standardised
      instruments that are available in German language and present data regarding the
      validity and reliability of a structured guide for the integrated diagnosis of
      adult ADHD (IDA) which has been constructed in order to provide a feasible tool
      for diagnosis of ADHD. 

PMID- 23856942
TI  - [Nature meets nurture: the importance of epigenetics for the aetiology of
      psychiatric diseases].
AB  - A successful therapy requires an understanding and investigation of the aetiology
      of a disease. Psychiatric diseases represent a special challenge, because
      environmental factors may play a crucial role in their development as well as
      possible physiological and genetic causes. Therefore, epigenetics has established
      itself to be a branch of research that studies the effect of environmental
      factors on the development of psychiatric diseases, leading to promising new
      approaches for diagnosis and therapy. 

PMID- 23856944
TI  - [Repeated measurement of memory with valenced test items: verbal memory, working
      memory and autobiographic memory].
AB  - A large number of questions in clinical and/or experimental neuropsychology
      require the multiple repetition of memory tests at relatively short intervals.
      Studies on the impact of the associated exercise and interference effects on the
      validity of the test results are rare. Moreover, hardly any neuropsychological
      instruments exist to date to record the memory performance with several parallel
      versions in which the emotional valence of the test material is also taken into
      consideration. The aim of the present study was to test whether a working memory
      test (WST, a digit-span task with neutral or negative distraction stimuli)
      devised by our workgroup can be used with repeated measurements. This question
      was also examined in parallel versions of a wordlist learning paradigm and an
      autobiographical memory test (AMT). Both tests contained stimuli with neutral,
      positive and negative valence. Twenty-four participants completed the memory
      testing including the working memory test and three versions of a wordlist and
      the AMT at intervals of a week apiece (measuring points 1. - 3.). The results
      reveal consistent performances across the three measuring points in the working
      and autobiographical memory test. The valence of the stimulus material did not
      influence the memory performance. In the delayed recall of the wordlist an
      improvement in memory performance over time was seen. The tests on working memory
      presented and the parallel versions for the declarative and autobiographical
      memory constitute informal economic instruments within the scope of the
      measurement repeatability designs. While the WST and AMT are appropriate for
      study designs with repeated measurements at relatively short intervals, longer
      intervals might seem more favourable for the use of wordlist learning paradigms. 

PMID- 23856945
TI  - [Bipolar disorder and compliance].
AB  - According to literature data the lack of compliance is a massive problem in up to
      50 % of the patients with bipolar affective disorders and can lead to severe long
      term complications in the further course of the diseases. In this case report we
      present various strategies that are intended to improve compliance. 

PMID- 23856946
TI  - [Upper extremity rehabilitation].

PMID- 23856947
TI  - PET imaging in a case of the semantic variant of primary progressive aphasia.
AB  - A 64-year-old right-handed Caucasian presented with a four-year history of word
      finding deficits and otherwise fluent speech production. Neurological examination
      remained unremarkable apart from the word finding impairment. Likewise,
      neuropsychological evaluation confirmed significantly reduced semantic word
      fluency. While brain MRI depicted only discrete anterior temporal atrophy, 18
      fluorodeoxyglucose PET showed clear hypometabolism of the anterior temporal pole
      bilaterally with left predominance. An imaging-supported diagnosis of the
      semantic variant of primary progressive aphasia was established in close
      accordance to recently published diagnostic criteria.The PET findings can be
      regarded as typical for this condition and PET imaging proved helpful to
      delineate other variants (non-fluent and logopenic) of primary progressive
      aphasia. 

PMID- 23856948
TI  - The regulatory challenge of electronic cigarettes.

PMID- 23856949
TI  - Mendelian randomization analysis of the effect of maternal homocysteine during
      pregnancy, as represented by maternal MTHFR C677T genotype, on birth weight.
AB  - BACKGROUND: We used Mendelian randomization analysis to investigate the causal
      relationship between maternal homocysteine level, as represented by maternal
      methylenetetrahydrofolate reductase (MTHFR) C677T genotype, with the birth weight
      of offspring. METHODS: We recruited women at 24 to 28 weeks' gestation who
      visited Ewha Womans University Hospital for prenatal care during the period from
      August 2001 to December 2003. A total of 473 newborns with a gestational age of
      at least 37 weeks were analyzed in this study. We excluded twin births and
      children of women with a history of gestational diabetes, gestational
      hypertension, or chronic renal disease. The association of maternal homocysteine
      concentration with the birth weight of infants was analyzed using 2-stage
      regression. RESULTS: MTHFR C677T genotype showed a dose-response association with
      homocysteine concentration for each additional T allele (Ptrend < 0.01). Birth
      weight decreased from 120 to 130 grams as maternal homocysteine level increased,
      while controlling for confounding factors; however, the association was of
      marginal significance (P = 0.06). CONCLUSIONS: Our results suggest an adverse
      relationship between maternal homocysteine level and birth weight. A reduction in
      homocysteine levels might positively affect birth outcomes.

PMID- 23856950
TI  - What's new on the post-ICU burden for patients and relatives?

PMID- 23856951
TI  - The avoidable death of a boy and the relentless pursuit for evidence.

PMID- 23856952
TI  - Viral involvement in the pathogenesis and clinical features of ophthalmic
      pterygium (Review).
AB  - Pterygium is a potentially vision-threatening fibrovascular lesion originating
      from the conjunctiva that often extends on the corneal surface. Although it has
      been extensively studied, its pathogenesis has yet to be fully elucidated. Recent
      evidence on molecular genetic abnormalities in pterygium suggested neoplastic
      changes of limbal stem cells potentially associated with exposure to ultraviolet
      (UV) light. Human papillomavirus (HPV) is an oncogenic virus, associated with
      squamo-proliferative lesions of the anogenital region, skin and oropharynx.
      Several studies have shown HPV involvement in the pathogenesis of conjunctival
      neoplastic lesions, including papilloma and squamous cell carcinoma. The
      involvement of HPV as a co-factor in the pathogenesis of pterygium, although
      suggested by several studies using PCR and immunohistochemical techniques,
      remains controversial. Moreover, a marked variation in the prevalence of HPV in
      ophthalmic pterygium has been reported by different studies. Ethnic
      susceptibility and methodological differences in the detection of HPV may account
      for this variation. Surgical excision, often using sophisticated techniques, is
      the standard current method of therapy for pterygium. However, recurrences are
      frequent and recurrent lesions tend to be more aggressive. If indeed HPV is
      involved in pterygium pathogenesis or recurrence, anti-viral medications or
      vaccination may be new options in pterygium therapy. 

PMID- 23856953
TI  - An unusual tumor in a rare localization: intravascular leiomyosarcoma of the
      cephalic vein. Case report.
AB  - Vascular leiomyosarcoma is a very rare soft tissue neoplasma, with a poor
      prognosis. We report a vascular leiomyosarcoma arising from an unusual site: the
      media-vascular wall of the cephalic vein. A 71-year-old man with a subcutaneous
      node on the volar side of right forearm, came to our attention with signs of
      vascular obstruction and venous stases, without functional or sensory loss of the
      right upper extremity. We successfully performed a surgical excision of the
      cancer with a wide margin resection. During surgery no ascellar lympnodes
      metastes were found. 4 months after surgery the wound had fully healed, and he
      suffered no effects by surgery, but he became lost to long-term follow-up and
      refused adjuvant radiotherapy or chemiotherapy. This case report shows that, in
      presence of venous stases or thrombosis signs of the upper extremity,
      leiomyosarcoma of the cephalic vein must be considered in the differential
      diagnosis among lung cancer, lymphoma or mesenchymal tumours.

PMID- 23856954
TI  - Early integration of palliative care services with standard oncology care for
      patients with advanced cancer.
AB  - Scientific advances in novel cancer therapeutics have led to remarkable changes
      in oncology practice and longer lives for patients diagnosed with incurable
      malignancies. However, the myriad options for treatment have established a
      culture of cancer care that has not been matched with a similar availability of
      efficacious supportive care interventions aimed at relieving debilitating
      symptoms due to progressive disease and treatment side effects. Accumulating data
      show that the introduction of palliative care services at the time of diagnosis
      of advanced cancer leads to meaningful improvement in the experiences of patients
      and family caregivers by emphasizing symptom management, quality of life, and
      treatment planning. In this review article, the rationale and evidence base for
      this model of early palliative care services integrated into standard oncology
      care are presented. In addition, the implications and limitations of the existing
      data to 1) elucidate the mechanisms by which early palliative care benefits
      patients and families; 2) guide the dissemination and application of this model
      in outpatient settings; and 3) inform health care policy regarding the delivery
      of high-quality, cost-effective, and comprehensive cancer care are discussed.

PMID- 23856962
TI  - Symbiosis: a symbiotic mosaic.

PMID- 23856968
TI  - Synthesis of thioether derivatives of quinazoline-4-one-2-thione and evaluation
      of their antiplatelet aggregation activity.
AB  - A series of 2-(arylmethylthio)-3-phenylquinazolin-4-one derivatives have been
      synthesized and their antiplatelet aggregation activities were assessed against
      ADP and arachidonic acid-induced platelet aggregation in human plasma. Among the
      tested thioethers, derivative 2, 3, 5 and 16 were the most potent compounds with
      satisfactory IC50 for inhibition of platelet aggregation induced by ADP. Analysis
      of global physicochemical parameters shows some correlations between activities
      and molecular volume and also surface area of the studied derivatives.

PMID- 23856969
TI  - Quercetin along with piperine prevents cognitive dysfunction, oxidative stress
      and neuro-inflammation associated with mouse model of chronic unpredictable
      stress.
AB  - Stress occurs in everyday life and persistence of it causes memory loss.
      Bioflavonoids like quercetin are reported to have poor bioavailability and
      limited therapeutic potential against stress induced neurological disorders.
      Therefore, the present study is an attempt to elucidate the therapeutic potency
      of combination of quercetin with piperine; a bioavailability enhancer against
      chronic unpredictable stress (CUS)-induced behavioral and biochemical
      alterations. Laca mice were subjected to a series of stressful events for a
      period of 28 days. Quercetin (20, 40 and 80 mg/kg, p.o.), piperine (20 mg/kg,
      p.o.) and their combinations were administered daily 30 min before CUS procedure.
      Piracetam (100 mg/kg, i.p.) served as a standard control. CUS caused impaired
      spatial navigation in Morris water maze test and poor retention in elevated plus
      maze task. Further, there was significant increase in brain oxidative stress
      markers and neuro-inflammation (TNF-alpha). This was coupled with marked rise in
      acetylcholinesterase and serum corticosterone levels. Co-administration of
      piperine with quercetin significantly elevated their potential to restore these
      behavioral, biochemical and molecular changes associated with mouse model of CUS.
      These results suggest that piperine enhances the neuroprotective effects of
      quercetin against CUS-induced oxidative stress, neuro-inflammation and memory
      deficits.

PMID- 23856970
TI  - Ambroxol inhibits rhinovirus infection in primary cultures of human tracheal
      epithelial cells.
AB  - The mucolytic drug ambroxol hydrochloride reduces the production of pro
      inflammatory cytokines and the frequency of exacerbation in patients with chronic
      obstructive pulmonary disease (COPD). However, the inhibitory effects of ambroxol
      on rhinovirus infection, the major cause of COPD exacerbations, have not been
      studied. We examined the effects of ambroxol on type 14 rhinovirus (RV14)
      infection, a major RV group, in primary cultures of human tracheal epithelial
      cells. RV14 infection increased virus titers and cytokine content in the
      supernatants and RV14 RNA in the cells. Ambroxol (100 nM) reduced RV14 titers and
      cytokine concentrations of interleukin (IL)-1beta, IL-6 and IL-8 in the
      supernatants and RV14 RNA in the cells after RV14 infection, in addition to
      reducing susceptibility to RV14 infection. Ambroxol also reduced the expression
      of intercellular adhesion molecule-1 (ICAM-1), the receptor for RV14, and the
      number of acidic endosomes from which RV14 RNA enters the cytoplasm. In addition,
      ambroxol reduced the activation of the transcription factor nuclear factor kappa
      B (NF-kappaB) in the nucleus. These results suggest that ambroxol inhibits RV14
      infection partly by reducing ICAM-1 and acidic endosomes via the inhibition of NF
      kappaB activation. Ambroxol may modulate airway inflammation by reducing the
      production of cytokines in rhinovirus infection.

PMID- 23856971
TI  - 2',4'-BNA bearing a chiral guanidinopyrrolidine-containing nucleobase with potent
      ability to recognize the CG base pair in a parallel-motif DNA triplex.
AB  - In order to expand the target sequence used in triplex DNA formation, seven novel
      nucleotide analogues were synthesized and incorporated into triplex-forming
      oligonucleotides by post-elongation modification approaches. Among them, ,
      equipped with a suitable restricted conformation of sugar and nucleobase
      moieties, was found to have the highest sequence-selectivity and affinity towards
      CG base pairs within double-stranded DNA. 

PMID- 23856972
TI  - Targeted metabolic profiling of hepatocellular carcinoma and hepatitis C using LC
      MS/MS.
AB  - Hepatitis C virus (HCV) infection of the liver is a global health problem and a
      major risk factor for the development of hepatocellular carcinoma (HCC).
      Sensitive methods are needed for the improved and earlier detection of HCC, which
      would provide better therapy options. Metabolic profiling of the high-risk
      population (HCV patients) and those with HCC provides insights into the process
      of liver carcinogenesis and possible biomarkers for earlier cancer detection.
      Seventy-three blood metabolites were quantitatively profiled in HCC (n = 30) and
      cirrhotic HCV (n = 22) patients using a targeted approach based on LC-MS/MS.
      Sixteen of 73 targeted metabolites differed significantly (p < 0.05) and their
      levels varied up to a factor of 3.3 between HCC and HCV. Four of these 16
      metabolites (methionine, 5-hydroxymethyl-2'-deoxyuridine, N2,N2
      dimethylguanosine, and uric acid) that showed the lowest p values were used to
      develop and internally validate a classification model using partial least
      squares discriminant analysis. The model exhibited high classification accuracy
      for distinguishing the two groups with sensitivity, specificity, and area under
      the receiver operating characteristic curve of 97%, 95%, and 0.98, respectively.
      A number of perturbed metabolic pathways, including amino acid, purine, and
      nucleotide metabolism, were identified based on the 16 biomarker candidates.
      These results provide a promising methodology to distinguish cirrhotic HCV
      patients, who are at high risk to develop HCC, from those who have already
      progressed to HCC. The results also provide insights into the altered metabolism
      between HCC and HCV. 

PMID- 23856974
TI  - Trauma-induced "Macklin effect" with pneumothorax and large pneumomediastinum,
      disguised by allergy.
AB  - A 56-year-old man presented spontaneously to the Emergency Department complaining
      of facial and neck oedema after assumption of nonsteroidal anti-inflammatory
      drugs (NSAIDS). The triage nurse assigned the patient to Accident & Emergency
      (A&E) doctor as probable allergic reaction to NSAIDS. Chest X-ray (CXR), ordered
      after 24 hours, revealed a huge subcutaneous chest and neck emphysema without
      clearly visible pneumothorax. Subsequent chest CT scan showed a small left
      pneumothorax and a large amount of air in the mediastinum. The patient was
      conservatively treated since he was eupnoeic and hemodynamically stable. The
      pathophysiology of pneumomediastinum was first described by Macklin in 1939. The
      Macklin effect involves alveolar ruptures with air dissection along
      bronchovascular sheaths to the mediastinum. In this case the patient did not
      report in his history a recent blunt thoracic trauma and the initial suspicion of
      an allergic reaction has prevented physicians to immediately achieve the correct
      diagnosis. 

PMID- 23856973
TI  - Therapeutic effects of thalidomide in hematologic disorders: a review.
AB  - The extensive autoimmune, anti-inflammatory, and anticancer applications of
      thalidomide have inspired a growing number of studies and clinical trials. As an
      inexpensive agent with relatively low toxicity, thalidomide is regarded as a
      promising therapeutic candidate, especially for malignant diseases. We review its
      therapeutic effects in hematology, including those on multiple myeloma,
      Waldenstroem macroglobulinemia, lymphoma, mantle-cell lymphoma, myelodysplastic
      syndrome, hereditary hemorrhagic telangiectasia, and graftversus-host disease.
      Most studies have shown satisfactory results, although several have reported the
      opposite. Aside from optimal outcomes, the toxicities and adverse effects of
      thalidomide should also be examined. The current work includes a discussion of
      the mechanisms through which the novel biological effects of thalidomide occur,
      although more studies should be devoted to this aspect. With appropriate
      safeguards, thalidomide may benefit patients suffering from a broad variety of
      disorders, particularly refractory and resistant diseases. 

PMID- 23856976
TI  - Sulfur and iron co-doped titanoniobate nanosheets: a novel efficient solid acid
      catalyst for alcoholysis of styrene epoxide at room temperature.
AB  - Sulfur and iron co-doped titanoniobate nanosheets were prepared and evaluated in
      alcoholysis of styrene epoxide. The resultant co-doped catalyst exhibited
      excellent catalytic performance (yield of 99% with methanol as the nucleophile in
      only 1 h at room temperature) and may act as a promising candidate in many acid
      catalyzed reactions. 

PMID- 23856975
TI  - Cultural differences define diagnosis and genomic medicine practice: implications
      for undiagnosed diseases program in China.
AB  - Despite the current acceleration and increasing leadership of Chinese genetics
      research, genetics and its clinical application have largely been imported to
      China from the Occident. Neither genetics nor the scientific reductionism
      underpinning its clinical application is integral to the traditional Chinese
      worldview. Given that disease concepts and their incumbent diagnoses are
      historically derived and culturally meaningful, we hypothesize that the cultural
      expectations of genetic diagnoses and medical genetics practice differ between
      the Occident and China. Specifically, we suggest that an undiagnosed diseases
      program in China will differ from the recently established Undiagnosed Diseases
      Program at the United States National Institutes of Health; a culturally
      sensitive concept will integrate traditional Chinese understanding of disease
      with the scientific reductionism of Occidental medicine. 

PMID- 23856977
TI  - Convenient syntheses of cyanuric chloride-derived NHC ligands, their Ag(I) and
      Au(I) complexes and antimicrobial activity.
AB  - Convenient syntheses of mono- and bis-imidazolium 1,3,5-triazine derivatives
      bearing piperidine and morpholine substituents are reported. In situ
      deprotonation of the mono-imidazolium salts and reaction with Ag2O or Au(tht)Cl
      (tht = tetrahydrothiophene) precursors affords the corresponding Ag(NHC)Cl and
      Au(NHC)Cl carbene complexes. In the presence of Ag(I) or Au(I) salts the bis
      imidazolium pincers eliminate the imidazolium group to afford -OMe or -NMe2
      substituted triazines depending on the solvent used. In solution, the Ag(I) and
      Au(I) complexes show a barrier to rotation about the Ctriazine-Namine bonds, with
      calculated DeltaG(?) barriers in the region of 70 kJ mol(-1). Single crystal X
      ray structures of several of the proligands and their corresponding Ag(I) and
      Au(I) complexes were obtained. These universally reveal an extended, rigidly
      planar pi-conjugated network between the triazine core,
      imidazolium/imidazolylidene substituents and exocyclic amine functions, to which
      the origin of the rotational barrier observed in solution is attributed. Only
      very weak Ntriazine-metal interactions are observed in the solid state, as
      indicated by small deviations of the CNHC-Ag-Cl bond angles from 180 degrees  and
      also supported by DFT calculations on the Ag(NHC)Cl complex (NHC = 4,6
      dipiperidinyl-2-methylimidazolylidene triazine). Preliminary antimicrobial
      susceptibility studies against five microorganisms (methicillin resistant
      Staphylococcus aureus NCTC 13277, S. aureus NCTC 6571, Pseudomonas aeruginosa
      NCTC 10662, Proteus mirabilis NCTC 11938 and Candida albicans ATCC 90028) show
      that the above triazine-based Ag-NHC complexes are active antimicrobial and
      antifungal agents.

PMID- 23856978
TI  - Higher frequency of rs4977574 (the G Allele) on chromosome 9p21.3 in patients
      with myocardial infarction as revealed by PCR-RFLP analysis.
AB  - Single Nucleotide Polymorphisms (SNPs) can genetically predispose individuals for
      certain diseases and therefore are of clinical significance. Myocardial
      infarction (MI) was investigated in large genetic association studies revealing
      novel SNPs associated with MI. rs4977574 is a non-protein coding SNP (A>G) that
      is located in proximity of cyclin-dependent kinase inhibitor 2A and B genes on
      chromosome 9p21.3. rs4977574 has been recently found to be associated with the
      early-onset of MI, and rs4977574 is characterized by a guanine nucleotide (G)
      instead of an adenine nucleotide (A). rs4977574 has been reported to increase the
      risk for MI by 28%. In this study, we developed a polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method for detecting
      rs4977574 in Turkish population that consisted of 28 controls without previous MI
      record and 44 patients with MI. An intergenic genomic region containing the
      target SNP was amplified by PCR using patient's genomic DNA. Amplified DNA
      fragments were digested with a restriction enzyme, HhaI that cuts the amplified
      sequence if only the sequence has GCGC that carries rs4977574. After digestion
      with HhaI, DNA fragments were visualized in order to detect genotypes. PCR-RFLP
      revealed that the frequency of rs4977574, the MI-associated allele (G), was 56.8%
      (25/44) in patients with MI and 33.9% (9.5/28) in controls; the frequency of
      rs4977574 in patients with MI was significantly higher compared to controls (P =
      0.027). Importantly, for the first time in this study, we have developed a novel
      PCR-RFLP method to detect the presence of rs4977574. 

PMID- 23856979
TI  - Usefulness of thiopurine metabolites in predicting azathioprine resistance in
      pediatric IBD patients.
AB  - Few data on azathioprine (AZA) therapy for inflammatory bowel disease (IBD) exist
      for children. We evaluated whether the 6-thioguanine nucleotides (6-TGN) level
      predicts AZA refractoriness in children with IBD and whether children benefit an
      AZA dose escalation. Seventy-eight children with IBD initially treated with an
      AZA dose of 1.5-2.5 mg/kg/day were retrospectively included. The dose was
      adjusted based on the clinical status. The receiver operating characteristic
      curve and logistic regression were used to determine predictors for AZA
      resistance. Initially, 18 of 40 (45%) patients receiving a dose of <2 mg/kg/day
      and 11 of 38 (28.9%) patients receiving a dose of 2-2.5 mg/kg/day achieved
      remission. The 6-TGN level above 250 pmol/8.10(8) RBCs was associated with a
      higher remission rate, though non-significant. Among 35 patients with a dose
      escalation due to treatment failure, 12 (34.3%) achieved remission (the median 6
      TGN level increased from 260 to 394 pmol/8.10(8) RBCs [P = .002]), 23 (67.6%)
      were AZA refractory. A 6-TGN level above 405 pmol/8.10(8) RBCs was the only
      predictor for AZA resistance (sensitivity 78.3%, specificity 75%, OR 10.8 [95%
      CI: 2.1-55.7, P = .004]). Serial metabolite monitoring is useful to identify
      children with IBD resistant to AZA. Children who cannot achieve remission despite
      a 6-TGN level above 405 pmol/8.10(8) RBCs should receive alternative therapies
      than dose increase.

PMID- 23856980
TI  - [Direct metabolites of ethanol as biological markers of alcohol use: basic
      aspects and applications].
AB  - In addition to self reports and questionnaires, biomarkers are of relevance in
      the diagnosis of and therapy for alcohol use disorders. Traditional biomarkers
      such as gamma-glutamyl transpeptidase or mean corpuscular volume are indirect
      biomarkers and are subject to the influence of age, gender and non-alcohol
      related diseases, among others. Direct metabolites of ethanol such as ethyl
      glucuronide (EtG), ethyl sulphate (EtS) and phosphatidylethanol (PEth) are direct
      metabolites of ethanol, that are positive after intake of ethyl alcohol. They
      represent useful diagnostic tools for identifying alcohol use even more
      accurately than traditional biomarkers. Each of these drinking indicators remains
      positive in serum and urine for a characteristic time spectrum after the
      cessation of ethanol intake - EtG and EtS in urine up to 7 days, EtG in hair for
      months after ethanol has left the body. Applications include clinical routine
      use, emergency room settings, proof of abstinence in alcohol rehabilitation
      programmes, driving under influence offenders, workplace testing, assessment of
      alcohol intake in the context of liver transplantation and foetal alcohol
      syndrome. Due to their properties, they open up new perspectives for prevention,
      interdisciplinary cooperation, diagnosis of and therapy for alcohol-related
      problems. 

PMID- 23856981
TI  - Effect of routine vaccination on aluminum and essential element levels in preterm
      infants.

PMID- 23856982
TI  - Ocular morbidity among school-going children in the Union Territory of
      Chandigarh.
AB  - Schoolchildren in India are susceptible to various types of ocular morbidities.
      Early detection through regular surveys helps in prompt treatment and prevention
      of blindness. The aim of this study was to estimate the prevalence of ocular
      morbidity among schoolchildren aged 6-16 years and to determine their socio
      demographic risk factors. This cross-sectional study includes government and
      private schools in Chandigarh. The study was conducted during August 2010 to
      December 2010. The World Health Organization 30-cluster sampling technique was
      used to cover an optimum sample size of 9,067 students in 30 schools from 169
      schools in Chandigarh with proportional allocation in different classes.
      Statistical analysis was done using SPSS version 15.0. Qualitative data was
      analysed using the Chi squared test. Logistic regression analysis was performed
      to identify risk factors. Prevalence rates of refractive error, colour-blindness,
      squint, and vitamin A deficiency were found to be 29.3, 1.2, 0.8 and 0.05 %,
      respectively, with an overall prevalence of ocular morbidity of 30.4 %. The
      prevalence of ocular morbidity was significantly higher among female students and
      among those studying in private schools. The prevalence rate increased
      significantly with age. A high prevalence of treatable or preventable ocular
      morbidity was observed among school-going children, and refractive error was the
      most common problem.

PMID- 23856983
TI  - Intravitreal silicone oil induced changes in corneal biomechanics.
AB  - Our aim was to detect the early effects of pars plana vitrectomy (PPV) combined
      with intravitreal silicone oil (SO) on corneal biomechanics. 19 eyes underwent
      PPV with SO tamponade (group 1) and 16 eyes underwent. PPV without tamponade
      (group 2). Corneal biomechanical parameters were measured preoperatively and at
      the first postoperative month by ocular response analyzer. The mean preoperative
      intraocular pressure (IOP) by Goldmann applanation tonometry (GAT) and the mean
      corneal-compensated intraocular pressure (IOPcc) were significantly lower in
      group 1 than group 2 (p = 0.005, p = 0.002, respectively). The mean preoperative
      corneal hysteresis (CH) and corneal resistance factor (CRF) were significantly
      higher in group 1 than group 2 (p = 0.017, p = 0.002, respectively). However, the
      difference in Goldmann-correlated intraocular pressure (IOPg) between the groups
      was not significant (p = 0.360). In group 1, IOPcc, IOPg and IOP-GAT
      significantly increased postoperatively (p = 0.002, p = 0.004, p = 0.002,
      respectively) but CH and CRF decreased (p = 0.007, p = 0.153, respectively). In
      group 2, IOPcc, IOPg and IOP (GAT) increased postoperatively but the differences
      were not significant (p = 0.851, p = 0.693, p = 0.336, respectively). The mean
      CRF increased significantly (p = 0.026) postoperatively but the decrease in CH
      was not significant (p = 0.196). Statistically significant differences were found
      in the changes of preoperative and postoperative means of IOPcc, IOPg, IOP-GAT
      and CRF between the groups (p = 0.024, p = 0.037, p = 0.014, p = 0.006,
      respectively). However, the difference in the decreases in CH between the two
      groups was not statistically significant (p = 0.206). SO tamponade may affect
      corneal biomechanical parameters in the early postoperative period, which may be
      related to the surgery itself, SO tamponade or IOP changes.

PMID- 23856985
TI  - Recurrent granular cell tumor of the anal-perianal region: how much anal
      sphincter can be resected?

PMID- 23856984
TI  - Anatomic subsite of primary colorectal cancer and subsequent risk and
      distribution of second cancers.
AB  - BACKGROUND: Individuals with a history of colorectal cancer (CRC) have an
      increased risk of subsequent cancer. In this study, the authors used cancer
      registry data to evaluate whether this increased risk of cancer after CRC
      differed by anatomic subsite of a first CRC. METHODS: Individuals diagnosed with
      a first primary CRC between 1992 and 2009 were identified from 12 Surveillance,
      Epidemiology, and End Results (SEER) cancer registries. Standardized incidence
      ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparing the
      incidence of subsequent cancers in these patients who had an index CRC versus the
      cancer incidence rates in the general population. SIRs were calculated for
      cancers at anatomic sites within and outside the colorectum in analyses
      stratified by subsite of the index CRC. RESULTS: Cancer incidence rates were
      significantly higher in individuals who had a previous CRC than in the general
      population (SIR, 1.15; 95% CI, 1.13-1.16). Individuals with an index CRC located
      between the transverse and descending colon experienced the greatest increased
      risk both overall (SIR, 1.29-1.33) and particularly with respect to the risk of a
      second CRC (SIR, 2.53-3.35). The incidence of small intestinal cancer was
      elevated significantly regardless of the index CRC subsite (SIR, 4.31; 95% CI,
      3.70-4.77), and the incidence of endometrial cancer was elevated in those who had
      an index CRC in the proximal colon (SIR, 1.37-1.79). CONCLUSIONS: The risk of
      second cancer after CRC differs by anatomic site of the first tumor and is
      particularly pronounced for those with prior CRC located in the transverse to
      descending colon. The mechanisms underlying this pattern of second cancer risk
      remain unknown.

PMID- 23856986
TI  - Single vesicle biochips for ultra-miniaturized nanoscale fluidics and single
      molecule bioscience.
AB  - One of the major bottlenecks in the development of biochips is maintaining the
      structure and function of biomolecules when interfacing them with hard matter
      (glass, plastics, metals, etc.), a challenge that is exacerbated during
      miniaturization that inevitably increases the interface to volume ratio of these
      devices. Biochips based on immobilized vesicles circumvent this problem by
      encapsulating biomolecules in the protective environment of a lipid bilayer, thus
      minimizing interactions with hard surfaces. Here we review the development of
      biochips based on arrays of single nanoscale vesicles, their fabrication via
      controlled self-assembly, and their characterization using fluorescence
      microscopy. We also highlight their applications in selected fields such as
      nanofluidics and single molecule bioscience. Despite their great potential for
      improved biocompatibility, extreme miniaturization and high throughput, single
      vesicle biochips are still a niche technology that has yet to establish its
      commercial relevance. 

PMID- 23856987
TI  - The hundredth case of sclerosing epithelioid fibrosarcoma (SEF).
AB  - Sclerosing Epithelioid Fibrosarcoma (SEF) is a rare and distinct variant of low
      grade fibrosarcoma, found mainly in deep soft tissue of adult extremities. We
      report a case of Sclerosing Epithelioid Fibrosarcoma of soft tissue, which
      developed in a 69-year-old woman who presented a tumor involving the fourth
      finger of her right foot and which has not progressed much in size during the
      three months prior the surgical excision. Our patient is the hundredth case of
      Sclerosing Epithelioid Fibrosarcoma reported in literature since 1995, thus
      confirming the rarity of the tumor. Our experience showed that it is important to
      make an early diagnosis, in consideration of the clinical aggressiveness of this
      cancer. Another important aspect concerns the postoperative follow-up. The
      monitoring of PET-CT technique , although not standardized, could become part of
      proceedings of therapy and follow-up of tumor, thus allowing oncological
      radicality and avoid large amputations. To date, 24 months after diagnosis of
      SEF, our patient feels well, attends our outpatient clinic regularly and shows no
      evidence of relapse and/or metastasis.

PMID- 23856988
TI  - Complexation with organometallic ruthenium pharmacophores enhances the ability of
      4-anilinoquinazolines inducing apoptosis.
AB  - The complexation with organoruthenium fragments confers 4-anilinoquinazoline
      pharmacophores with higher potential for inducing cellular apoptosis while the
      highly inhibitory activity of 4-anilinoquinazolines against EGFR and the
      reactivity of the ruthenium centre to 9-ethylguanine are well preserved. 

PMID- 23856989
TI  - Assessment of the effect of bariatric surgery on obstructive sleep apnea at two
      postoperative intervals.
AB  - BACKGROUND: Studies have reported significant improvement of obstructive sleep
      apnea (OSA) in obese patients after bariatric surgery (BS). Weight loss following
      BS is rapid in the first few months, but it can take at least 1 year to reach the
      final result. The aim of this study is to measure the effect of BS on various
      clinical, respiratory, and sleep parameters of OSA at two postoperative
      intervals. METHODS: Prospectively, all patients being evaluated for BS underwent
      a polysomnography (PSG). Patients diagnosed with OSA preoperatively were invited
      to undergo a PSG at least 6 months postoperatively and if OSA persisted, again at
      least 12 months postoperatively. RESULTS: One hundred ten patients underwent a
      first postoperative PSG 7.7 months after surgery. The mean apnea-hypopnea index
      (AHI) significantly decreased from 39.5 to 15.6/h. In 58.2 %, the AHI was reduced
      to below 10 and in 25.5 % to below 5. Fifty patients underwent a first PSG 7.1
      months and a second PSG 16.9 months after surgery. The mean AHI decreased from
      49.1 to 22.7 to 17.4/h following BS. CONCLUSIONS: BS initiates dramatic
      improvement and even remission of clinical and sleep parameters during the first
      7 months, which continues at a slower rate over the next 10 months. We recommend
      a follow-up PSG after surgery to check for residual disease and if necessary
      retritration of continuous positive airway pressure, which may lead to higher
      treatment compliance.

PMID- 23856990
TI  - Assessing psychosocial functioning of bariatric surgery candidates with the
      Minnesota multiphasic personality inventory-2 restructured form (MMPI-2-RF).
AB  - BACKGROUND: Psychological comorbidity is common in bariatric surgery candidates.
      Many multidisciplinary teams incorporate psychometric testing to screen for
      psychological factors that, if left unattended, may negatively impact surgical
      results. Here, we report descriptive findings and empirical correlates of
      Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF)
      scales among of bariatric surgery candidates undergoing a pre-surgical
      psychological evaluation. METHODS: The sample consisted of male (n = 324) and
      female (n = 658) patients seeking bariatric surgery who were administered the
      MMPI-2-RF at their psychological evaluation. Psychosocial and medical variables
      were retrospectively coded from the patients' medical records. These criteria
      included history/current mental health diagnoses and treatments, maladaptive
      eating behaviors/diagnoses, past/current substance use, abuse history, sleep
      apnea, and denial of surgery. RESULTS: Descriptive analyses demonstrated similar
      findings for male and female candidates and replicated previous reports. MMPI-2
      RF scales measuring emotional dysfunction were associated with maladaptive eating
      patterns, a history of Major Depressive Disorder, and previous suicide attempts.
      Scale scores measuring behavioral dysfunction were associated with current/past
      substance use and previous physical abuse. MMPI-2-RF scale scores measuring
      somatic problems were associated with a higher BMI at the time of surgery, sleep
      apnea diagnosis/adherence, physical/sexual abuse history, active mood disorder,
      previous mental health diagnoses, and maladaptive eating patterns. CONCLUSIONS:
      The MMPI-2-RF can aid in identifying a broad range of psychological comorbidity
      among bariatric surgery candidates. When used in conjunction with a pre-surgical
      psychological interview, it can aid in the assessment of psychological factors
      relevant to pre-surgical psychological assessment of bariatric surgery
      candidates.

PMID- 23856991
TI  - Laparoscopic sleeve gastrectomy compared to a multidisciplinary weight loss
      program for obesity--effects on body composition and protein status.
AB  - BACKGROUND: Optimal obesity therapy is a matter of debate. Besides weight
      reduction, other criteria such as safety and nutritional status are of relevance.
      Therefore, we compared a favored surgical intervention with the most effective
      conservative treatment regarding anthropometry and nutritional status. METHODS:
      Fifty-four obese patients were included who underwent laparoscopic sleeve
      gastrectomy (LSG, n = 27) or a 52-week multidisciplinary intervention program
      (MIP, n = 27) for weight loss. Body weight, body composition assessed by
      bioelectrical impedance analysis, and serum protein levels were measured before
      and within 12 months after intervention. RESULTS: After 1 year of observation,
      excess weight loss was more pronounced following LSG (65 %) compared to MIP (38
      %, p < 0.001). In both groups, body fat was clearly reduced, but a higher
      reduction occurred in the LSG group. However, protein status deteriorated
      particularly in the LSG group. Within 1 year, body cell mass declined from 37.1
      to 26.9 kg in the LSG group, but only from 35.7 to 32.2 kg in the MIP group. This
      resulted in an increased mean extracellular mass/body cell mass ratio (1.42
      versus 1.00, p < 0.001), in a decreased mean phase angle (4.4 degrees  versus 6.6
      degrees , p < 0.001), and in a lower prealbumin level in serum (p < 0.02) in the
      LSG group compared to the MIP group. CONCLUSIONS: LSG, compared to MIP, was more
      effective regarding excess weight loss and body fat loss within 1 year, however,
      induced more pronounced muscle mass and protein loss, possibly requiring
      particular interventions such as exercise or protein supplements.

PMID- 23856992
TI  - miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin
      by targeting Bcl-2.
AB  - Drug resistance is one of the leading causes of chemotherapy failure in cancer
      treatment. MicroRNAs (miRNAs or miRs) are short non-coding RNA molecules that
      post-transcriptionally regulate gene expression and play a critical role in
      diverse biological processes. In this study, we report that miR-503 regulates the
      resistance of non-small cell lung cancer cells to cisplatin. The expression of
      miR-503 was decreased in the cisplatin-resistant non-small cell lung cancer
      cells, A549/CDDP, compared with the parental A549 cells. The overexpression of
      miR-503 sensitized the A549/CDDP cells to cisplatin, whereas the inhibition of
      miR-503 in the A549 cells increased resistance to cisplatin. Mechanistically, miR
      503 specifically targeted Bcl-2, an anti-apoptotic protein upregulated in the
      A549/CDDP cells. The ectopic expression of miR-503 reduced the Bcl-2 protein
      level and sensitized the A549/CDDP cells to cisplatin-induced apoptosis. Taken
      together, our results suggest that miR-503 regulates cell apoptosis, at least in
      part by targeting Bcl-2, and thus modulates the resistance of non-small cell lung
      cancer cells to cisplatin. 

PMID- 23856993
TI  - Acid-base disorders: paracrine regulation of acid-base balance.

PMID- 23856994
TI  - Renal artery stenosis: renal artery stenosis-predicting responses to
      revascularization.

PMID- 23856995
TI  - The primary glomerulonephritides: a systems biology approach.
AB  - Our understanding of the pathogenesis of most primary glomerular diseases,
      including IgA nephropathy, membranous nephropathy and focal segmental
      glomerulosclerosis, is limited. Advances in molecular technology now permit
      genome-wide, high-throughput characterization of genes and gene products from
      biological samples. Comprehensive examinations of the genome, transcriptome,
      proteome and metabolome (collectively known as omics analyses), have been applied
      to the study of IgA nephropathy, membranous nephropathy and focal segmental
      glomerulosclerosis in both animal models and human patients. However, most omics
      studies of primary glomerular diseases, with the exception of large genomic
      studies, have been limited by inadequate sample sizes and the lack of kidney
      specific data sets derived from kidney biopsy samples. Collaborative efforts to
      develop a standardized approach for prospective recruitment of patients,
      scheduled monitoring of clinical outcomes, and protocols for sampling of kidney
      tissues will be instrumental in uncovering the mechanisms that drive these
      diseases. Integration of molecular data sets with the results of clinical and
      histopathological studies will ultimately enable these diseases to be
      characterized in a comprehensive and systematic manner, and is expected to
      improve the diagnosis and treatment of these diseases. 

PMID- 23856999
TI  - Ischemia-reperfusion injury accelerates human antibody-mediated transplant
      vasculopathy.
AB  - BACKGROUND: The pathogenesis of transplant vasculopathy (TV) is a multifactorial
      process. We hypothesized that ischemia-reperfusion injury and antibody-mediated
      damage contribute to the development of TV. METHODS: Human vessels were procured
      from nine separate donors undergoing cardiac surgery and stored in saline
      solution on ice until transplantation. BALB/c Rag2IL-2Rgamma mice were
      transplanted with a human vessel graft on day 0. Purified anti-human leukocyte
      antigen class I antibody (W6/32), isotype control antibody, or saline was
      injected into recipient mice weekly until day 42, at which point the degree of
      intimal expansion (IE) of vessels was assessed by histologic analysis. RESULTS:
      We found that a prolonged cold ischemia time (6-12 hr) alone did not induce IE.
      In mice that received antibody where vessels were transplanted within 6 hr of
      procurement, no IE was observed. By contrast, in vessels exposed to more than 6
      hr cold ischemia, both W6/32 antibody (30.4%+/-6.9%) and isotype control antibody
      (39.5%+/-6.0%) promoted significant IE (P<0.05 vs. saline [12.4%+/-1.7%]).
      Importantly, the isotype control antibody did not cross-react with human tissue.
      Interestingly, the number of mouse Fc-receptor-positive cells was significantly
      increased in human vessels exposed to more than 6 hr cold ischemia but only in
      the presence of antibody (P<0.05). CONCLUSIONS: Antibody, regardless of its
      specificity, may promote IE in human vessels that are injured through cold
      ischemia via interaction with Fc-receptor-positive cells. This highlights the
      importance of controlling the degree of cold ischemia in clinical transplantation
      in an effort to reduce the risk of TV development.

PMID- 23856996
TI  - The applicability of eGFR equations to different populations.
AB  - The Cockcroft-Gault equation for estimating glomerular filtration rate has been
      learnt by every generation of medical students over the decades. Since the
      publication of the Modification of Diet in Renal Disease (MDRD) study equation in
      1999, however, the supremacy of the Cockcroft-Gault equation has been
      relentlessly disputed. More recently, the Chronic Kidney Disease Epidemiology
      (CKD-EPI) consortium has proposed a group of novel equations for estimating
      glomerular filtration rate (GFR). The MDRD and CKD-EPI equations were developed
      following a rigorous process, are expressed in a way in which they can be used
      with standardized biomarkers of GFR (serum creatinine and/or serum cystatin C)
      and have been evaluated in different populations of patients. Today, the MDRD
      Study equation and the CKD-EPI equation based on serum creatinine level have
      supplanted the Cockcroft-Gault equation. In many regards, these equations are
      superior to the Cockcroft-Gault equation and are now specifically recommended by
      international guidelines. With their generalized use, however, it has become
      apparent that those equations are not infallible and that they fail to provide an
      accurate estimate of GFR in certain situations frequently encountered in clinical
      practice. After describing the processes that led to the development of the new
      GFR-estimating equations, this Review discusses the clinical situations in which
      the applicability of these equations is questioned. 

PMID- 23857001
TI  - Predictive factors of allosensitization after immunosuppressant withdrawal in
      recipients of long-term cultured islet cell grafts.
AB  - BACKGROUND: Islet transplantation has been reported to induce allosensitization
      in the majority of type 1 diabetic recipients of fresh or shortly incubated islet
      grafts prepared from one to three donors. METHODS: We examined the appearance of
      human leukocyte antigen (HLA) antibodies after withdrawal of immunosuppressants
      in 35 type 1 diabetic recipients of islet cell grafts prepared from a median of 6
      donors (range, 2-11), cultured for longer periods, and characterized for their
      cellular composition. Immunosuppression consisted of antithymocyte globulin
      induction followed by mycophenolate mofetil plus calcineurin inhibitors (n=28,
      with 7 also receiving steroids) or sirolimus with (n=3) or without calcineurin
      inhibitors (n=4). Both the complement-dependent cytotoxicity (CDC) assay (class
      I) and the solid-phase flow-based Luminex method (class I and II) were used to
      identify HLA antibodies. RESULTS: Immunosuppressant withdrawal resulted in CDC
      positivity for class I antibodies in only 6% of patients. However, the majority
      became positive for class I antibodies (72%) or class II antibodies (72%) in the
      Luminex assay; positivity was not correlated to a higher number of donors or HLA
      mismatches, but with a lower beta-cell purity; use of steroids reduced de novo
      positivity for Luminex class I antibodies. CONCLUSION: Allosensitization to
      cultured human islet cell grafts was low when assessed by CDC assay but high in
      Luminex. No correlation was found with the number of donors but risk was higher
      for grafts with lower beta-cell purity.

PMID- 23857000
TI  - Release of soluble CD30 after allogeneic stimulation is mediated by memory T
      cells and regulated by IFN-gamma and IL-2.
AB  - BACKGROUND: Membrane CD30 is an important costimulatory molecule for activated T
      lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for
      predicting outcome in kidney transplantation. METHODS: We investigated the
      kinetics of CD30 expression on CD4 and CD8 T-cell populations and the source of
      sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies
      against interferon (IFN)-gamma and other cytokines on sCD30 release and the
      involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for
      sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on
      allostimulated CD3 lymphocytes were evaluated in dialysis patients and matched
      controls. RESULTS: Allogeneic stimulation resulted in conversion of naive
      responder cells to central memory CD4 cells (P<0.001 at 96 hr) and effector CD8
      cells (P<0.01 at 120 hr), which was accompanied by increased CD30 expression.
      Release of sCD30 was attributed mainly to central memory cells, and
      neutralization of IFN-gamma (P<0.001) and interleukin (IL)-2 (P<0.001) impaired
      the release of sCD30 during allostimulation but did not alter the levels of
      ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a
      similar way as in healthy controls. CONCLUSIONS: Allostimulation results in the
      up-regulation of the T-cell activation marker CD30 on CD4 as well as CD8 memory T
      cells and increased release of sCD30 from these cells in an IFN-gamma- and IL-2
      dependent manner. These results may explain clinical findings on the suitability
      of sCD30 and IFN-gamma- and IL-2-producing T cells for immune monitoring of
      kidney transplant recipients before and after transplantation.

PMID- 23857002
TI  - Modified multivisceral transplantation in the rat.

PMID- 23857003
TI  - Posttransplantation hepatitis E: transfusion-transmitted hepatitis rising from
      the ashes.

PMID- 23857004
TI  - Relapsing brucellosis after liver transplantation in a child: what is the
      appropriate regimen and duration of therapy?

PMID- 23857005
TI  - Two "lost boys of Sudan" undergo liver transplantation: infectious disease
      issues.

PMID- 23857006
TI  - Extracorporeal photopheresis for chronic GVHD: case report after adult bowel
      abdominal wall transplantation.

PMID- 23857008
TI  - Reaction of trisubstituted alkenes with iron porphyrin carbenes: facile synthesis
      of tetrasubstituted dienes and cyclopentadienes.
AB  - The unprecedented reaction of trisubstituted alkenes with iron porphyrin carbenes
      has been successfully developed. Both multiply substituted 1,3-butadiene and
      cyclopentadiene products are readily accessible with high efficiency and
      selectivity in good yields. 

PMID- 23857007
TI  - Resolvin D1 reduces deterioration of tight junction proteins by upregulating HO-1
      in LPS-induced mice.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is
      characterized by increased pulmonary permeability with high mortality. Resolvin
      D1 (RvD1), which has potent anti-inflammatory and pro-resolving activity, can
      attenuate pulmonary edema in the animal model of ALI. However, the mechanism
      underlying the protection of RvD1 on pulmonary edema is still unknown. Here we
      explore the effects and mechanism of RvD1 on the disruption of tight junction
      protein that results in the permeability edema in a model of lipopolysaccharide
      (LPS)-induced ALI. The severity of pulmonary edema was assessed by wet-to-dry
      rate and Evans blue infiltration; expressions of tight junction (TJ) proteins
      occludin and zona occludin-1 (ZO-1) were examined by immunofluorescence staining
      and western blot; mRNA in lung tissue was studied by real time-PCR; the TUNEL kit
      was performed for the detection of apoptosis of pulmonary barrier. Twenty-four
      hours after LPS inhalation by mice, wet-to-dry rate and Evans blue infiltration
      indicated that pretreatment with RvD1 relieved the pulmonary edema and pulmonary
      capillary permeability. Moreover, RvD1 attenuated the LPS-induced deterioration
      of TJ protein ZO-1 and occludin significantly. And we found that RvD1 increased
      heme oxygenase-1 (HO-1) expression contributed to the protection on the
      deterioration of TJs. In addition, we found that RvD1 could reduce pulmonary
      cellular apoptosis in LPS-induced mice. In conclusion, RvD1 possesses the ability
      that relieves the pulmonary edema and restores pulmonary capillary permeability
      and reduces disruption of TJs in LPS-induced ALI of mice, at least in part, by
      upregulating HO-1 expression.

PMID- 23857009
TI  - Balsam of Peru: past and future.
AB  - Balsam of Peru (BOP) is a well-known contact allergen that is one of the most
      prevalent in the United States. For some patients allergic to BOP, external
      avoidance of fragrance is not enough to eliminate their dermatitis. A BOP
      avoidance diet has been shown to help many of these patients. This article
      reviews BOP allergens found in food. A special patch test series of allergens
      found in BOP along with data regarding which foods contain specific BOP
      constituents makes it possible to design potential targeted, refined, and
      simplified diets for BOP systemic contact dermatitis. 

PMID- 23857010
TI  - Nickel exposure from keys: alternatives for protection and prevention.
AB  - BACKGROUND: Keys are an important exposure source of metal allergens to consumers
      and confer a significant problem for nickel-allergic individuals because of
      repeated daily use. OBJECTIVES: The aims of this study were to investigate the
      frequency of nickel and cobalt release in keys and to consider the effectiveness
      of coatings for preventing metallic allergen release from common metal allergen
      releasing keys. METHODS: Keys from a variety of common stores were nickel and
      cobalt spot tested. Nickel-releasing keys were coated with enamel sprays,
      subjected to a use test, and retested to assess for metal allergen release.
      RESULTS: Of 55 tested keys, 80% showed a strong positive result to the nickel
      spot test. None of the tested keys exhibited cobalt release. No keys initially
      released nickel after enamel coatings. Key coatings chipped at the portion
      inserted into a lock after 30 insertions, and keys were found to release nickel.
      The handle of the key was not found to release nickel after 60 insertions.
      CONCLUSIONS: Nickel release from keys is very common; nickel-allergic consumers
      should consider purchasing keys that do not release nickel (eg, brass, anodized).
      Enamel coating may be useful in protecting nickel-sensitive individuals from
      their keys but cannot consistently prevent nickel-release from portions used
      frequently.

PMID- 23857012
TI  - Systemic contact dermatitis to topical clioquinol/hydrocortisone combination
      cream.

PMID- 23857011
TI  - Winter season, frequent hand washing, and irritant patch test reactions to
      detergents are associated with hand dermatitis in health care workers.
AB  - BACKGROUND: Irritant hand dermatitis (IHD) is common in health care workers.
      OBJECTIVE: We studied endogenous irritant contact dermatitis threshold by patch
      testing and exogenous factors such as season and hand washing for their
      association with IHD in health care workers. METHODS: Irritant patch testing with
      sodium lauryl sulfate (SLS), sodium hydroxide, and benzalkonium chloride at
      varying concentrations was measured in 113 health care workers. Examination for
      hand dermatitis occurred at 1-month intervals for a period of 6 months in the
      Midwestern United States. RESULTS: Positive patch testing to low-concentration
      SLS was associated with IHD (P = 0.0310) after adjusting for age, sex, ethnicity,
      season, history of childhood flexural dermatitis, mean indoor relative humidity,
      and glove and hand sanitizer usage. Subjects with a positive patch test to SLS
      were 78% more likely to have occurrence of IHD (incidence rate ratio [IRR] =
      1.78; 95% confidence interval [CI], 0.92-3.45). Hand washing frequency (>=10
      times a day; IRR = 1.55; 95% CI, 1.01-2.39) and cold season (IRR = 2.76; 95% CI,
      1.35-5.65) were associated with IHD. No association was found between history of
      childhood flexural dermatitis and IHD in this population. CONCLUSIONS: Both
      genetic and environmental factors are important in the etiology of IHD and should
      be considered in designing strategies to protect, educate, and treat susceptible
      individuals.

PMID- 23857013
TI  - Low-nickel diet scoring system for systemic nickel allergy.
AB  - BACKGROUND: Consumption of nickel in the diet leads to spongiotic dermatitis in a
      dose-related fashion in individuals who are allergic to nickel. Dietary
      modification to reduce nickel intake leads to resolution of this dermatitis.
      OBJECTIVE: This study aims to create an evidence-based, user-friendly diet to
      assist patients in reducing dietary nickel intake. METHODS: Food and Drug
      Administration data on the nickel content of foods were combined with serving
      size information to calculate the upper limit of nickel per serving for a variety
      of foods. Based on these calculations, a point system was created that allows
      patients to reduce their nickel intake below the typical threshold for
      elicitation of the spongiotic dermatitis. CONCLUSIONS: A simplified point-based
      diet can help patients with dermatitis due to dietary nickel consumption.

PMID- 23857014
TI  - Serum resistin in patients with allergic contact dermatitis.

PMID- 23857015
TI  - Patch test reactions associated with sunscreen products and the importance of
      testing to an expanded series: retrospective analysis of North American Contact
      Dermatitis Group data, 2001 to 2010.
AB  - BACKGROUND: Both active and inactive ingredients in sunscreen may cause contact
      dermatitis. OBJECTIVES: This study aimed to describe allergens associated with a
      sunscreen source. METHODS: A cross-sectional analysis of patients patch tested by
      the North American Contact Dermatitis Group between 2001 and 2010 was performed.
      RESULTS: Of 23,908 patients patch tested, 219 (0.9%) had sunscreen coded as an
      allergen source. Patients who were male, with occupational dermatitis, or older
      (older than 40 years) had significantly lower rates of allergic reactions to
      sunscreens; the most commonly affected areas were the face and exposed sites (P <
      0.0001). The top 3 most frequent allergens in sunscreens were benzophenone-3
      (70.2% for 10% concentration, 64.4% for 3% concentration), DL-alpha-tocopherol
      (4.8%), and fragrance mix I (4.0%). Less than 40% of positive patch test
      reactions were detected by the North American Contact Dermatitis Group screening
      series of 65 to 70 allergens. CONCLUSIONS: A supplemental antigen series is
      important in detecting allergy to sunscreens.

PMID- 23857016
TI  - Effects of alitretinoin on quality of life of patients having chronic hand
      eczema: an observational study.
AB  - Chronic hand eczema (CHE) is a common disease that has a major impact on
      patients' health and on society. AIM: The purpose of this observational, open
      label study was to assess the efficacy of treatment with 30 mg/d of oral
      alitretinoin on the quality of life (QoL) in a group of patients affected by CHE.
      METHODS: This study included 15 patients, all suffering from severe CHE
      refractory to treatment with potent topical corticosteroids, who underwent
      treatment with 30 mg/d of alitretinoin for a period of 3 months. At the 1- and 3
      month points, together with a clinical evaluation, the QoL of these patients were
      evaluated by the Dermatology Life Quality Index and visual analog scale (EQ5D
      VAS). RESULTS: The oral administration of alitretinoin led to a notable QoL
      improvement among the patients, as shown by the statistically significant
      improvement in the Dermatology Life Quality Index and in the EQ5D-VAS after 1 and
      3 months of therapy.

PMID- 23857017
TI  - Association between the IL10 -1082A>G (rs1800896) single-nucleotide polymorphism
      and atopic dermatitis: a systematic review and meta-analysis.
AB  - BACKGROUND: The potentially functionally relevant IL10 -1082A>G (rs1800896)
      promoter region single-nucleotide polymorphism has been implicated in the
      pathogenesis of atopic dermatitis (AD). Although this relationship has been
      studied extensively, these association studies were limited by small sample size.
      OBJECTIVE: To increase statistical power and obtain a more precise estimate of
      the association, literature evidence on IL10 -1082A>G and AD was assessed by
      conducting a systematic review and meta-analysis. METHODS: This study followed
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. PubMed (MEDLINE), EMBASE, Scopus, and HuGE Literature Finder
      literature databases were systematically searched for relevant studies. Summary
      odds ratios and corresponding 95% confidence intervals were estimated using the
      fixed-effect inverse variance analysis method for allelic (G vs A) and genotypic
      comparisons. RESULTS: Meta-analysis of 7 studies (n = 849 cases and 1195
      controls) found a nonsignificant association between the IL10 -1082A>G
      polymorphism and AD (allelic odds ratio, 1.02; 95% confidence interval, 0.88
      1.19; P = 0.77). CONCLUSIONS: This study was unable to find a direct association
      between IL10 -1082A>G and AD. Further studies are needed to reveal the
      contributions of haplotype and gene-gene and gene-environment interaction effects
      involving this single-nucleotide polymorphism to AD.

PMID- 23857018
TI  - Compound allergy to a lipophilic gel containing vitamin E acetate and
      cyclopentasiloxane.

PMID- 23857019
TI  - Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity
      reactions to metallic implants.
AB  - BACKGROUND: Metal hypersensitivity reactions to implanted devices remain a
      challenging and controversial topic. Diagnostic criteria and methods are not well
      delineated. OBJECTIVE: Diagnostic criteria for hypersensitivity reactions after
      metallic device implantation are evaluated in this study by a multinational group
      of patch testers using Thyssen's previously published criteria. METHODS: A total
      of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013
      American Contact Dermatitis Society meetings answered a survey regarding their
      opinions on topics relating to metal hypersensitivity. CONCLUSIONS: Four major
      and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found
      the following criteria useful (major criteria): chronic dermatitis beginning
      weeks to months after metallic implantation, eruption overlying the metal
      implant, positive patch test to a metal component of the implant, and complete
      clearing after removal of the potentially allergenic implant. Minor criteria
      (<61% of respondents) were as follows: systemic allergic dermatitis reaction,
      therapy-resistant dermatitis, morphology consistent with dermatitis, histology
      consistent with allergic contact dermatitis, and a positive in vitro test to
      metals (eg, lymphocyte transformation test). In the challenging situation such as
      a symptomatic or failing orthopedic device, applying these 4 major criteria and
      the 5 supportive minor criteria may be useful for guiding decision making.

PMID- 23857020
TI  - The first case of imported relapsing fever in Japan.
AB  - Tick-borne relapsing fever (TBRF) is endemic in discrete areas throughout the
      world; however, a domestic or imported case of relapsing fever has not been
      reported in Japan. Here, we report the first imported case. A previously healthy
      20-year-old woman presented to our hospital on October 8, 2010, because of
      recurrent fever and lower leg pain. Before consultation, she had experienced four
      febrile episodes at 10-12-day intervals after returning from her stay in
      Uzbekistan from 1 to 8 September. Giemsa stain of peripheral blood showed
      Borrelia spirochetes. The spirochete was identified as Borrelia persica by
      sequencing of the amplicons of flaB using polymerase chain reaction and
      phylogenetic analysis. The patient was diagnosed with TBRF, and she completed a
      10-day course of minocycline 100 mg twice daily. After treatment, her periodic
      fever subsided. Physicians should be aware of TBRF in patients with recurrent
      fever who have returned from TBRF-endemic countries, including areas of the
      former USSR.

PMID- 23857021
TI  - Two cases of Plasmodium falciparum malaria in the Netherlands without recent
      travel to a malaria-endemic country.
AB  - Recently, two patients of African origin were given a diagnosis of Plasmodium
      falciparum malaria without recent travel to a malaria-endemic country. This
      observation highlights the importance for clinicians to consider tropical malaria
      in patients with fever. Possible transmission routes of P. falciparum to these
      patients will be discussed. From a public health perspective, international
      collaboration is crucial when potential cases of European autochthonous P.
      falciparum malaria in Europe re considered.

PMID- 23857022
TI  - Avian hosts of West Nile virus in Arizona.
AB  - West Nile virus (WNV) causes sporadic outbreaks of human encephalitis in Phoenix,
      Arizona. To identify amplifying hosts of WNV in the Phoenix area, we blood
      sampled resident birds and measured antibody prevalence following an outbreak in
      the East Valley of metropolitan Phoenix during summer, 2010. House sparrow
      (Passer domesticus), house finch (Haemorhous mexicanus), great-tailed grackle
      (Quiscalus mexicanus), and mourning dove (Zenaida macroura) accounted for most
      WNV infections among locally resident birds. These species roost communally after
      early summer breeding. In September 2010, Culex vector-avian host contact was 3
      fold greater at communal bird roosts compared with control sites, as determined
      by densities of resting mosquitoes with previous vertebrate contact (i.e., blood
      engorged or gravid mosquitoes). Because of the low competence of mourning doves,
      these were considered weak amplifiers but potentially effective free-ranging
      sentinels. Highly competent sparrows, finches, and grackles were predicted to be
      key amplifying hosts for WNV in suburban Phoenix.

PMID- 23857023
TI  - First genetic detection of Coxiella burnetii in Zambian livestock.
AB  - Q fever is a widespread zoonosis caused by Coxiella burnetii, an obligate
      intracellular gram-negative bacterium. The investigation of C. burnetii infection
      in Zambian livestock was carried out using molecular detection techniques. A
      total of 489 cattle and 53 goat blood samples were collected from Chama, Chongwe,
      Monze, and Petauke districts in Zambia. Molecular screening by polymerase chain
      reaction was performed using C. burnetii-species-specific primers. In total, 38
      cattle and 4 goat samples were positive. The prevalence of C. burnetii differed
      among the four sites, with Chama (Eastern province) recording the highest,
      although Monze (Southern province) did not record any case of the bacteria. This
      study reports the first genetic detection of C. burnetii in Zambia.

PMID- 23857025
TI  - Comment to Masaki Fujioka et al. to their accepted letter to the editor:
      vascularized bone graft is a better option for the reconstruction of maxillary
      defects.

PMID- 23857024
TI  - Randomized, double-blinded, phase 2 trial of WR 279,396 (paromomycin and
      gentamicin) for cutaneous leishmaniasis in Panama.
AB  - In this randomized, double-blinded Phase 2 trial, 30 patients with Leishmania
      panamensis cutaneous leishmaniasis were randomly allocated (1:1) to receive once
      daily topical treatment with WR 279,396 (15% paromomycin + 0.5% gentamicin) or
      Paromomycin Alone (15% paromomycin) for 20 days. The index lesion cure rate after
      6 months follow-up was 13 of 15 (87%) for WR 279,396 and 9 of 15 (60%) for
      Paromomycin Alone (P = 0.099). When all treated lesions were included, the final
      cure rate for WR 279,398-treated patients was again 87%, but the final cure rate
      for Paromomycin Alone-treated patients was 8 of 15 (53.3%; P = 0.046). Both
      creams were well tolerated with mild application site reactions being the most
      frequent adverse event. The increased final cure rate in the WR 279,396 group in
      this small Phase 2 study suggests that the combination product may provide
      greater clinical benefit than paromomycin monotherapy against L. panamensis
      cutaneous leishmaniasis.

PMID- 23857026
TI  - Individualized optimal surgical extent of the lateral neck in papillary thyroid
      cancer with lateral cervical metastasis.
AB  - Despite an excellent prognosis, cervical lymph node (LN) metastases are common in
      patients with papillary thyroid cancer (PTC). The presence of metastasis is
      associated with an increased risk of locoregional recurrence, which significantly
      impairs quality of life and may decrease survival. Therefore, it has been an
      important determinant of the extent of lateral LN dissection in the initial
      treatment of PTC patients with lateral cervical metastasis. However, the optimal
      extent of therapeutic lateral neck dissection (ND) remains controversial.
      Optimizing the surgical extent of LN dissection is fundamental for balancing the
      surgical morbidity and oncological benefits of ND in PTC patients with lateral
      neck metastasis. We reviewed the currently available literature regarding the
      optimal extent of lateral LN dissection in PTC patients with lateral neck
      metastasis. Even in cases with suspicion of metastatic LN at the single lateral
      level or isolated metastatic lateral LN, the application of ND including all
      sublevels from IIa and IIb to Va and Vb may be overtreatment, due to the surgical
      morbidity. When there is no suspicion of LN metastasis at levels II and V, or
      when multilevel aggressive neck metastasis is not found, sublevel IIb and Va
      dissection may not be necessary in PTC patients with lateral neck metastasis.
      Thus consideration of the individualized optimal surgical extent of lateral ND is
      important when treating PTC patients with lateral cervical metastasis. 

PMID- 23857028
TI  - Biomechanical evaluation of meniscal root repair: a porcine study.
AB  - PURPOSE: Meniscal root repair is commonly practised using transtibial pull-out
      sutures. The purpose of the study was to investigate whether these are effective
      in restoring contact of the root to its footprint and a normal loading pattern of
      the cartilage under restricted loading conditions as used post-operatively.
      METHODS: First, a transtibial pull-out suture was simulated using porcine menisci
      (n = 10). It was repetitively loaded (100*; 1-10 N) and the elongation of the
      suture determined. In the second part of the study, porcine knees (n = 8) were
      subjected to repetitive low-level femoro-tibial loads (50 cycles; 100 N). A
      displacement sensor measured the deformation of the cartilage in the area of
      femoro-tibial contact. The residual deformation of the cartilage, which results
      from its viscoelastic behaviour, was determined as a measure of the local stress.
      Three scenarios were investigated: meniscal root intact, detached, and repaired.
      RESULTS: Repetitive loading caused a median suture elongation of 3.8 mm. Residual
      deformation of the cartilage was increased (p = 0.047) with the root detached.
      Root repair could not restore it to normal (n.s.). CONCLUSIONS: In this model,
      meniscus root repair was not effective in restoring the normal loading pattern of
      the cartilage because cyclic loading caused an elongation of the repair. CLINICAL
      RELEVANCE: In practice, this effect might impair the healing of repaired meniscal
      roots to the tibial bone.

PMID- 23857029
TI  - In silico study on the inhibitory interaction of drugs with wild-type CYP2D6.1
      and the natural variant CYP2D6.17.
AB  - The natural variant of the cytochrome P450 enzyme CYP2D6.1, CYP2D6.17, is most
      common in African populations, has three amino acid substitutions (T107I, R296C,
      and S486T) compared to the wild-type, and is known to have a different ligand
      preference from CYP2D6.1. It is becoming increasingly important to understand
      differences in the metabolism of medicines in different ethnic groups in order to
      assess the relevance of clinical data from different countries. This study
      investigated differences in the inhibition profiles of drugs for CYP2D6 with
      respect to gene polymorphisms. Firstly, we used computer docking with six drugs
      to several CYP2D6.1 structures, sampled from the trajectory of MD simulations,
      and calculated MM-GB/SA scores representing binding free energies. We then used
      regression analysis to predict the potency with which drugs inhibited CYP2D6.1
      based on MM-GB/SA scores. The pKi-values obtained were in good agreement with
      experimental values measured for the six drugs (r(2) = 0.81). We carried out the
      same analysis for CYP2D6.17 and the pKi-values calculated were also in good
      agreement with experimental values (r(2) = 0.92). Finally, we were able to
      successfully explain the different abilities of CYP2D6.1 and CYP2D6.17 to
      metabolize drugs in different ethnic groups with reference to their 3D
      structures.

PMID- 23857030
TI  - Antivenom activity of triterpenoid (C34H68O2) from Leucas aspera Linn. against
      Naja naja naja venom induced toxicity: antioxidant and histological study in
      mice.
AB  - The isolated and identified triterpenoid, 1-hydroxytetratriacontane-4-one
      (C34H68O2), obtained from the methanolic leaf extract of Leucas aspera Linn. was
      explored for the first time for antisnake venom activity. The plant (L. aspera
      Linn.) extract significantly antagonized the spectacled cobra (Naja naja naja)
      venom induced lethal activity in a mouse model. It was compared with commercial
      antiserum obtained from King Institute of Preventive Medicine (Chennai, Tamil
      Nadu, India). N. naja naja venom induced a significant decrease in antioxidant
      superoxide dismutase, glutathione (GSH) peroxidase, catalase, reduced GSH and
      glutathione-S-transferase activities and increased lipid peroxidase (LPO)
      activity in different organs such as heart, liver, kidney and lungs. The
      histological changes following the antivenom treatment were also evaluated in all
      these organs. There were significant alterations in the histology. Triterpenoid
      from methanol extract of L. aspera Linn. at a dose level of 75 mg per mouse
      significantly attenuated (neutralized) the venom-induced antioxidant status and
      also the LPO activity in different organs. 

PMID- 23857031
TI  - Exposure to priority organochlorine contaminants in the Italian general
      population. Part 2: Fifteen priority polychlorinated biphenyl congeners in blood
      serum.
AB  - Concentrations of 36 polychlorinated biphenyl (PCB) congeners were measured in
      serum of 372 Italian residents of general population living in Novafeltria,
      Pavia, and Milan. Total PCB level differed significantly between these sites (p <
      0.0001) with median concentrations of 836.50, 1354.57, and 2062.08 pmol/g lipid,
      respectively. However, there is no evidence for the difference in distribution of
      total PCB levels by genders. Total dioxin-like PCBs differed significantly (p <
      0.0001) between the sites (median 109.78, 50.88, and 166.99 pmol/g lipid,
      respectively) and genders of Novafeltria and Pavia (p = 0.011 and 0.009,
      respectively). PCB 138, 153, 170, and 180 differed significantly between the
      places of residence (p < 0.0001) with higher values in Milan population. In the
      overall population, total PCB and PCB 138, 153, 156, 170, and 180 correlated
      positively with age (correlations range between 0.320 and 0.569, p < 0.0001). In
      Novafeltria, the correlations ranged between 0.545 and 0.670, and in Pavia, the
      correlations ranged between 0.516 and 0.666. In Milan, correlations with age
      range between 0.327 and 0.417 for total PCB and congeners 138, 153, and 180. With
      an exception of PCB 170, there was no evidence of significant difference in the
      distribution of most abundant PCB congeners and total PCB across the body mass
      index categories.

PMID- 23857032
TI  - Exposure to priority organochlorine contaminants in the Italian general
      population. Part 1. Eight priority organochlorinated pesticides in blood serum.
AB  - Despite extensive use of organochlorinated pesticides (OCPs) such as
      dichlorodiphenyltrichloroethane (DDT) in Italy in the 1940s to 1970s, especially
      for public health control of malaria mosquitoes, information on their exposure
      levels among the general population is limited. These OCPs can be a source of
      health risk to human. A total of 137 blood samples were collected from residents
      of the general population of three Italian towns, Novafeltria, Pavia and Milan,
      to determine the levels of eight OCPs in blood serum. The concentrations of beta
      hexachlorocyclohexane, hexachlorobenzene (HCB), 1,1-dichloro-2-(o-chlorophenyl)-2
      (p-chlorophenyl)ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'
      DDE), 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 1,1-dichloro-2,2
      bis (4-chlorophenyl)ethane, 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)
      ethane and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane were measured by gas
      chromatography-mass spectrometry. Variations in serum concentrations of OCPs with
      respect to place of residence, gender, age and body mass index (BMI) were
      evaluated by non-parametric tests. p,p'-DDE and HCB were the most abundant and
      major contributors of total OCP concentration. Their levels differed
      significantly between the three towns with a trend Milan > Novafeltria > Pavia (p
      < 0.0001). Females had significantly higher concentrations of HCB and p,p'-DDE
      than males in the overall population sample. HCB concentrations were
      significantly higher in females than in males of Milan (p = 0.029). We observed
      positive correlations of p,p'-DDE and HCB with age in Novafeltria subjects (r =
      0.468, p = 0.004). Total OCP concentrations differed significantly across BMI
      categories (p = 0.018) in overall population. We have demonstrated a clear
      pattern of the main OCPs in a fairly large population. Generally, our study
      provides information on OCPs exposure among the Italian general population and
      provides indications for further investigations.

PMID- 23857033
TI  - [The nerve of things].

PMID- 23857035
TI  - Prevention of venous thromboembolism in acutely ill medical patients after the
      results of recent trials with the new oral anticoagulants.
AB  - Venous thromboembolism (VTE) is a common potentially life-threatening
      complication in acutely ill medical patients; over 70 % of the fatal episodes of
      pulmonary embolism during hospitalization occur in non-surgical patients. In the
      absence of thromboprophylaxis, the incidence of venographically detected deep
      vein thrombosis is about 15 % in medical patients. Several trials and meta
      analyses have clearly demonstrated the prophylactic role of unfractionated
      heparin, low molecular weight heparin and fondaparinux. Although over the past
      few years the knowledge of epidemiology, clinical features and prophylaxis in
      medical patients has significantly improved, there remain a number of
      controversial areas that require further investigation. Newer VTE risk assessment
      models have been proposed to select high risk hospitalized medical patients, but
      they still require external validation; scarce data are available to stratify
      patients to identify their individual bleeding risk. The optimal duration of
      thromboprophylaxis in medical patients is still a matter of debate; currently,
      extended prophylaxis after discharge is not recommended, but it may be required
      for subgroup of patients with persistently high VTE risk and a negligible risk of
      bleeding. Based on the results of recent studies, the new oral anticoagulants
      appear to have a very limited role, if any. However, a better risk stratification
      of patients who have a persistently increased risk of VTE is warranted to improve
      the risk to benefit profile of any anticoagulant drug to be used in this setting.

PMID- 23857036
TI  - Effect of High-Intensity interval training versus moderate continuous training on
      24-h blood pressure profile and insulin resistance in patients with chronic heart
      failure.
AB  - In patients with chronic heart failure (CHF) blood pressure (BP) control,
      represents a relevant target of management. This study evaluated the effect of
      different intensities exercise training on 24-h ambulatory BP profile and insulin
      resistance in patients with CHF. Thirty-six CHF patients with left ventricular
      ejection fraction <40%, were randomized to high-intensity interval training (HIT)
      or moderate continuous training (MIT) for 12 weeks. HIT consisted in treadmill
      exercise at ~75-80% of heart rate reserve (HRR), alternated with active pauses at
      45-50% of HRR. MIT consisted in continuous treadmill at ~45-60% of HRR. Peak VO2
      and anaerobic threshold increased significantly with both HIT and MIT, without
      significant differences between the two training programs. 24-h, systolic and
      diastolic BP decreased with both HIT and MIT. The same occurred for day-time and
      night-time systolic and diastolic BP. The decrease in day-time diastolic BP was
      slightly but significantly greater in HIT. Both HIT and MIT induced a significant
      decrease in fasting glucose and insulin, whereas HOMA-IR decreased significantly
      only after HIT. In patients with CHF exercise training reduces BP throughout the
      day, without substantial differences between moderate and more vigorous exercise
      intensity, with a small exception for day-time diastolic BP. HIT was more
      effective in improving insulin resistance.

PMID- 23857037
TI  - Would apixaban be a good option for extended anticoagulation in venous
      thromboembolism?

PMID- 23857038
TI  - Cellular blebs: pressure-driven, axisymmetric, membrane protrusions.
AB  - Blebs are cellular protrusions that are used by cells for multiple purposes
      including locomotion. A mechanical model for the problem of pressure-driven blebs
      based on force and moment balances of an axisymmetric shell model is proposed.
      The formation of a bleb is initiated by weakening the shell over a small region,
      and the deformation of the cellular membrane from the cortex is obtained during
      inflation. However, simply weakening the shell leads to an area increase of more
      than 4%, which is physically unrealistic. Thus, the model is extended to include
      a reconfiguration process that allows large blebs to form with small increases in
      area. It is observed that both geometric and biomechanical constraints are
      important in this process. In particular, it is shown that although blebs are
      driven by a pressure difference across the cellular membrane, it is not the
      limiting factor in determining bleb size.

PMID- 23857039
TI  - Megacolon for a giant faecaloma with unlucky outcome: case report and review of
      the literature.
AB  - We herein report a case of megacolon with fecaloma in an 83-year-old man who
      presented with constipation, no intestinal occlusion, and a left
      hydroureteronephrosis, with A.S.A. 4. The patient asymptomatic, was treated
      Primariely with laxatives. During the conservative therapy the patient presented
      an abrupt abdominal distension with a bowel obstruction and abdominal compartment
      syndrome. After the laparotopy and a Hartmann left colon resection the patient
      died for cardiovascular and metabolic complications. The aim of this report is to
      give a brief review of this entity and discuss the treatment options for these
      cases.

PMID- 23857040
TI  - Updates in the management of high-grade glioma.
AB  - The management of high-grade glioma (HGG) has evolved significantly over the last
      decade. Patients are managed in a multidisciplinary team setting in order to
      ensure their care is guided by the most current evidenced based treatments. The
      outcome in patients with HGG, while still poor, has improved in terms of both
      survival and quality of life during illness. This review discusses a number of
      developments seen in the management of HGG over the last 5 years.

PMID- 23857041
TI  - Automatic administration of propofol and remifentanil guided by the bispectral
      index during rigid bronchoscopic procedures: a randomized trial.
AB  - BACKGROUND: Anesthesia for rigid bronchoscopic procedures is a demanding
      procedure. Automatic titration of propofol and remifentanil to maintain the
      bispectral index (BIS) within the recommended range (40-60) has been reported
      during routine surgical procedures. The aim of the present study was to evaluate
      its use during rigid bronchoscopy. METHODS: Patients were enrolled in a
      randomized study comparing manual target-controlled infusion of propofol and
      remifentanil (manual TCI group) with automatic titration guided by the BIS (dual
      loop group). Categorical variables were compared by the Fisher's exact test, and
      continuous variables (median [interquartile range 25-75]) were compared by the
      Mann-Whitney test. RESULTS: Thirty-four patients were included in the manual TCI
      group and 33 were included in the dual-loop group. Baseline characteristics were
      well balanced between the groups. Intervention by the anesthesiologist in charge
      to modify propofol and/or remifentanil targets in the dual-loop group was not
      necessary. Percentage of time spent in the BIS interval (40-60) was similar in
      the manual TCI and dual-loop groups (69% [48-79] vs 70% [58-80], respectively).
      Durations of induction and of maintenance and propofol and remifentanil doses
      were also similar between groups, except for the amount of propofol needed for
      induction (P = 0.002). Time to tracheal extubation was also similar. No case of
      intraoperational awareness was detected. CONCLUSION: The present study could not
      establish the superiority of automatic system over manual adjustment for
      bronchoscopy. Further studies with a different design and a larger number of
      patients are required to establish the place of automatic delivery of anesthetic
      agents. This study was registered at ClinicalTrials.gov number, NCT00571181.

PMID- 23857044
TI  - Neurodegenerative disease: can synucleinopathy and tauopathy be identified during
      life?

PMID- 23857046
TI  - Alzheimer disease: 'generation next' in Alzheimer disease genetic studies.

PMID- 23857050
TI  - Development of a Scale for Assessing Three Aspects of Sleep: Regularity, Quality,
      and Quantity.
AB  - Objectives: It is difficult to assess sleep habits using one factor (i.e., sleep
      duration) alone. Regularity and quality of sleep have to be considered to assess
      sleep accurately. However, to our knowledge there is no scale which scores the
      three factors simultaneously. The purpose of this study was to inspect the
      reliability and validity (content, construct, and discriminant validity) of a
      scale we developed to screen for poor sleep habits. This scale was constructed to
      assess three aspects of sleep: regularity, quality, and quantity. Methods:
      Subjects were 563 day workers (370 men and 193 women; average age = 40.4 yr) from
      the manufacturing and service industries. We created a 21-item questionnaire (7
      items for each of 3 factors) based on earlier studies and discussions with
      specialists. Reliability and construct validity of the questionnaire were
      assessed through item and factor analyses and Cronbach's alpha. In addition,
      subjects' scores were using principal component analysis, and subjects were
      classified according to their scores through a cluster analysis. We compared
      lifestyles, daytime sleepiness, stress, and chronic disease among the subjects to
      examine the instrument's discriminant validity. Results: Although our analysis
      revealed 6 items were invalid, the questionnaire assessed the three factors
      (regularity, quality and quantity) as expected: Cronbach's alpha was 0.744,
      0.757, and 0.548, respectively. Two of the 7 quantity items were identified as
      assessing regularity instead, but all other items performed as expected. Four
      items measuring insomnia (disturbance of sleep induction, disturbance of sound
      sleep, nocturnal awakening, and early morning awakening) included constant burden
      as a quality factor. Chi-squared tests showed that the ratio of participants who
      took good care of their health and had less stress and daytime sleepiness was
      significantly high in the highest-scoring group, while the ratio of people
      reporting stress and chronic disease was significantly high in the lowest-scoring
      group. Conclusions: The questionnaire we developed for assessing three factors of
      sleep (regularity, quality and quantity) was determined to have construct
      validity. However, since some items were excluded and some assessed into another
      factor, sufficient reliability and content validity were not found. Revision is
      needed to improve the scale's accuracy, and we also have to examine detailed
      discriminant validity controlling for factors such as age and sex.

PMID- 23857051
TI  - Effects of estrogen receptor alpha and beta on the expression of visfatin and
      retinol-binding protein 4 in 3T3-L1 adipocytes.
AB  - The aim of this study was to investigate the effects of estrogen and estrogen
      receptor alpha (ERalpha) and beta (ERbeta) on the expression of visfatin and
      retinol-binding protein 4 (RBP4) by treating 3T3-L1 adipocytes with estradiol
      (E2), estrogen receptor agonists and antagonists. Mature adipocytes were exposed
      to E2, the ERalpha agonist, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5
      triyl)trisphenol (PPT), the ERbeta agonist, 2,3-bis(4-hydroxyphenyl)
      propionitrile (DPN), E2 with the ERalpha antagonist, 1,3-bis(4-hydroxyphenyl)-4
      methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP), and
      E2 with the ERbeta antagonist, (5R, 11R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8
      chrysenediol [(R,R)-THC], at various concentrations. To determine the effects of
      ER subtypes on the expression of adipokines, quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) and western blot analyses were performed. E2
      concentrations of 10-5 and 10-6 mol/l induced a statistically significant
      increase in the expression of RBP4 (P=0.012 and P=0.011, respectively). In the
      cells treated with 10-5 mol/l PPT, RBP4 expression significantly increased
      (P<0.05) in a dose-dependent manner. Treatment with the ERalpha antagonist, MPP
      (10-5 mol/l), and E2 suppressed the expression of RBP4 (P=0.032). However, the
      expression of RBP4 was not significantly altered when the cells were treated with
      the ERbeta agonist or antagonist. The expression of visfatin was not affected by
      different concentrations of E2 and ERs. 17beta-estradiol significantly increased
      the secretion of RBP4 and upregulated RBP4 expression via ERalpha but not ERbeta
      in 3T3-L1 adipocytes. RBP4 expression was regulated by estrogen in the 3T3-L1
      adipocytes and this effect was selectively mediated by ERalpha.

PMID- 23857047
TI  - Advances in the genetics of Parkinson disease.
AB  - Parkinson disease (PD) is a multifactorial neurodegenerative disease that was
      long considered the result of environmental factors. In the past 15 years,
      however, a genetic aetiology for PD has begun to emerge. Here, we review results
      from linkage and next-generation sequencing studies of familial parkinsonism, as
      well as candidate gene and genome-wide association findings in sporadic PD. In
      these studies, many of the genetic findings overlap, despite different designs
      and study populations, highlighting novel therapeutic targets. The molecular
      results delineate a sequence of pathological events whereby deficits in synaptic
      exocytosis and endocytosis, endosomal trafficking, lysosome-mediated autophagy
      and mitochondrial maintenance increase susceptibility to PD. These discoveries
      provide the rationale, molecular insight and research tools to develop
      neuroprotective and disease-modifying therapies. 

PMID- 23857052
TI  - Exploiting CRISPR/Cas: interference mechanisms and applications.
AB  - The discovery of biological concepts can often provide a framework for the
      development of novel molecular tools, which can help us to further understand and
      manipulate life. One recent example is the elucidation of the prokaryotic
      adaptive immune system, clustered regularly interspaced short palindromic repeats
      (CRISPR)/CRISPR-associated (Cas) that protects bacteria and archaea against
      viruses or conjugative plasmids. The immunity is based on small RNA molecules
      that are incorporated into versatile multi-domain proteins or protein complexes
      and specifically target viral nucleic acids via base complementarity. CRISPR/Cas
      interference machines are utilized to develop novel genome editing tools for
      different organisms. Here, we will review the latest progress in the elucidation
      and application of prokaryotic CRISPR/Cas systems and discuss possible future
      approaches to exploit the potential of these interference machineries. 

PMID- 23857053
TI  - Membrane binding and insertion of a pHLIP peptide studied by all-atom molecular
      dynamics simulations.
AB  - Recent experiments in function mechanism study reported that a pH low-insertion
      peptide (pHLIP) can insert into a zwitterionic palmitoyloleoylphosphatidylcholine
      (POPC) lipid bilayer at acidic pH while binding to the bilayer surface at basic
      pH. However, the atomic details of the pH-dependent interaction of pHLIP with a
      POPC bilayer are not well understood. In this study, we investigate the detailed
      interactions of pHLIP with a POPC bilayer at acidic and basic pH conditions as
      those used in function mechanism study, using all-atom molecular dynamics (MD)
      simulations. Simulations have been performed by employing the initial
      configurations, where pHLIP is placed in aqueous solution, parallel to bilayer
      surface (system S), partially-inserted (system P), or fully-inserted (system F)
      in POPC bilayers. On the basis of multiple 200-ns MD simulations, we found (1)
      pHLIP in system S can spontaneously insert into a POPC bilayer at acidic pH,
      while binding to the membrane surface at basic pH; (2) pHLIP in system P can
      insert deep into a POPC bilayer at acidic pH, while it has a tendency to exit,
      and stays at bilayer surface at basic pH; (3) pHLIP in system F keeps in an alpha
      helical structure at acidic pH while partially unfolding at basic pH. This study
      provides at atomic-level the pH-induced insertion of pHLIP into POPC bilayer. 

PMID- 23857054
TI  - Chemical and colloidal stability of carboxylated core-shell magnetite
      nanoparticles designed for biomedical applications.
AB  - Despite the large efforts to prepare super paramagnetic iron oxide nanoparticles
      (MNPs) for biomedical applications, the number of FDA or EMA approved
      formulations is few. It is not known commonly that the approved formulations in
      many instances have already been withdrawn or discontinued by the producers; at
      present, hardly any approved formulations are produced and marketed. Literature
      survey reveals that there is a lack for a commonly accepted physicochemical
      practice in designing and qualifying formulations before they enter in vitro and
      in vivo biological testing. Such a standard procedure would exclude inadequate
      formulations from clinical trials thus improving their outcome. Here we present a
      straightforward route to assess eligibility of carboxylated MNPs for biomedical
      tests applied for a series of our core-shell products, i.e., citric acid, gallic
      acid, poly(acrylic acid) and poly(acrylic acid-co-maleic acid) coated MNPs. The
      discussion is based on physicochemical studies (carboxylate
      adsorption/desorption, FTIR-ATR, iron dissolution, zeta potential, particle size,
      coagulation kinetics and magnetization measurements) and involves in vitro and in
      vivo tests. Our procedure can serve as an example to construct adequate physico
      chemical selection strategies for preparation of other types of core-shell
      nanoparticles as well. 

PMID- 23857056
TI  - Integrated self-assembly of the Mms6 magnetosome protein to form an iron
      responsive structure.
AB  - A common feature of biomineralization proteins is their self-assembly to produce
      a surface consistent in size with the inorganic crystals that they produce. Mms6,
      a small protein of 60 amino acids from Magnetospirillum magneticum strain AMB-1
      that promotes the in vitro growth of superparamagnetic magnetite nanocrystals,
      assembles in aqueous solution to form spherical micelles that could be visualized
      by TEM and AFM. The results reported here are consistent with the view that the N
      and C-terminal domains interact with each other within one polypeptide chain and
      across protein units in the assembly. From studies to determine the amino acid
      residues important for self-assembly, we identified the unique GL repeat in the N
      terminal domain with additional contributions from amino acids in other
      positions, throughout the molecule. Analysis by CD spectroscopy identified a
      structural change in the iron-binding C-terminal domain in the presence of Fe3+.
      A change in the intrinsic fluorescence of tryptophan in the N-terminal domain
      showed that this structural change is transmitted through the protein. Thus, self
      assembly of Mms6 involves an interlaced structure of intra- and inter-molecular
      interactions that results in a coordinated structural change in the protein
      assembly with iron binding. 

PMID- 23857055
TI  - Melatonin in Alzheimer's disease.
AB  - Alzheimer's disease (AD), an age-related neurodegenerative disorder with
      progressive cognition deficit, is characterized by extracellular senile plaques
      (SP) of aggregated beta-amyloid (Abeta) and intracellular neurofibrillary
      tangles, mainly containing the hyperphosphorylated microtubule-associated protein
      tau. Multiple factors contribute to the etiology of AD in terms of initiation and
      progression. Melatonin is an endogenously produced hormone in the brain and
      decreases during aging and in patients with AD. Data from clinical trials
      indicate that melatonin supplementation improves sleep, ameliorates sundowning
      and slows down the progression of cognitive impairment in AD patients. Melatonin
      efficiently protects neuronal cells from Abeta-mediated toxicity via antioxidant
      and anti-amyloid properties. It not only inhibits Abeta generation, but also
      arrests the formation of amyloid fibrils by a structure-dependent interaction
      with Abeta. Our studies have demonstrated that melatonin efficiently attenuates
      Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still
      not fully understood, a direct regulatory influence of melatonin on the
      activities of protein kinases and protein phosphatases is proposed. Additionally,
      melatonin also plays a role in protecting the cholinergic system and in anti
      inflammation. The aim of this review is to stimulate interest in melatonin as a
      potentially useful agent in the prevention and treatment of AD. 

PMID- 23857057
TI  - Quorum quenching in culturable phyllosphere bacteria from tobacco.
AB  - Many Gram-negative plant pathogenic bacteria employ a N-acylhomoserine lactone
      (AHL)-based quorum sensing (QS) system to regulate their virulence traits. A
      sustainable biocontrol strategy has been developed using quorum quenching (QQ)
      bacteria to interfere with QS and protect plants from pathogens. Here, the
      prevalence and the diversity of QQ strains inhabiting tobacco leaf surfaces were
      explored. A total of 1177 leaf-associated isolates were screened for their
      ability to disrupt AHL-mediated QS, using the biosensor Chromobacterium violaceum
      CV026. One hundred and sixty-eight strains (14%) are capable of interfering with
      AHL activity. Among these, 106 strains (63%) of the culturable quenchers can
      enzymatically degrade AHL molecules, while the remaining strains might use other
      QS inhibitors to interrupt the chemical communication. Moreover, almost 79% of
      the QQ strains capable of inactivating AHLs enzymatically have lactonase
      activity. Further phylogenetic analysis based on 16S rDNA revealed that the leaf
      associated QQ bacteria can be classified as Bacillus sp., Acinetobacter sp.,
      Lysinibacillus sp., Serratia sp., Pseudomonas sp., and Myroides sp. The naturally
      occurring diversity of bacterial quenchers might provide opportunities to use
      them as effective biocontrol reagents for suppressing plant pathogen in situ. 

PMID- 23857059
TI  - miR-29 represses the activities of DNA methyltransferases and DNA demethylases.
AB  - Members of the microRNA-29 (miR-29) family directly target the DNA
      methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of
      miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the
      miR-29 family are currently thought to repress DNA methylation and suppress
      tumorigenesis by protecting against de novo methylation. Here, we report that
      members of the miR-29 family repress the activities of DNA methyltransferases and
      DNA demethylases, which have opposing roles in control of DNA methylation status.
      Members of the miR-29 family directly inhibited DNA methyltransferases and two
      major factors involved in DNA demethylation, namely tet methylcytosine
      dioxygenase 1 (TET1) and thymine DNA glycosylase (TDG). Overexpression of miR-29
      upregulated the global DNA methylation level in some cancer cells and
      downregulated DNA methylation in other cancer cells, suggesting that miR-29
      suppresses tumorigenesis by protecting against changes in the existing DNA
      methylation status rather than by preventing de novo methylation of DNA. 

PMID- 23857060
TI  - TMPRSS4 as a poor prognostic factor for triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is characterized by the lack of
      immunohistochemical staining for estrogen receptors (ER), progesterone receptors
      (PR), and lack of overexpression or amplification of human epidermal growth
      factor receptor 2 (HER2). Our aim was to investigate the expression of
      transmembrane protease, serine 4 (TMPRSS4) in TNBC patients and its possible
      relationship to the outcome of the disease. A total of 72 TNBC patients and 109
      non-TNBC patients who were diagnosed between 2003 and 2008 were enrolled in this
      study. Immunohistochemistry was used to compare the expression pattern of TMPRSS4
      in TNBC and non-TNBC groups, and the prognostic significance was assessed by
      Kaplan-Meier analysis and Cox proportional hazards regression in TNBC patients.
      The rate of high expression of TMPRSS4 was significantly higher in TNBC group
      than that in non-TNBC group. High expression of TMPRSS4 was significantly
      correlated with lymph node metastasis, histological grade, and tumor size. TNBC
      patients with high TMPRSS4 expression showed the poorer overall survival (OS) and
      disease-free survival (DFS) than those patients with low TMPRSS4 expression. In
      multivariate analysis, only lymph node metastasis and TMPRSS4 expression were the
      independent prognostic factors for OS and DFS in TNBC. Our study provides
      evidence that TMPRSS4 expression is associated with lymph node metastasis, tumor
      size, and histological grade in TNBC patients, and also is an independent
      prognostic factor for TNBC. 

PMID- 23857058
TI  - The potential role of lycopene for the prevention and therapy of prostate cancer:
      from molecular mechanisms to clinical evidence.
AB  - Lycopene is a phytochemical that belongs to a group of pigments known as
      carotenoids. It is red, lipophilic and naturally occurring in many fruits and
      vegetables, with tomatoes and tomato-based products containing the highest
      concentrations of bioavailable lycopene. Several epidemiological studies have
      linked increased lycopene consumption with decreased prostate cancer risk. These
      findings are supported by in vitro and in vivo experiments showing that lycopene
      not only enhances the antioxidant response of prostate cells, but that it is even
      able to inhibit proliferation, induce apoptosis and decrease the metastatic
      capacity of prostate cancer cells. However, there is still no clearly proven
      clinical evidence supporting the use of lycopene in the prevention or treatment
      of prostate cancer, due to the only limited number of published randomized
      clinical trials and the varying quality of existing studies. The scope of this
      article is to discuss the potential impact of lycopene on prostate cancer by
      giving an overview about its molecular mechanisms and clinical effects. 

PMID- 23857061
TI  - Near infrared optical visualization of epidermal growth factor receptors levels
      in COLO205 colorectal cell line, orthotopic tumor in mice and human biopsies.
AB  - In this study, we present the applicability of imaging epidermal growth factor
      (EGF) receptor levels in preclinical models of COLO205 carcinoma cells in vitro,
      mice with orthotopic tumors and ex vivo colorectal tumor biopsies, using EGF
      labeled with IRDye800CW (EGF-NIR). The near infrared (NIR) bio-imaging of COLO205
      cultures indicated specific and selective binding, reflecting EGF receptors
      levels. In vivo imaging of tumors in mice showed that the highest
      signal/background ratio between tumor and adjacent tissue was achieved 48 hours
      post-injection. Dissected colorectal cancer tissues from different patients
      demonstrated ex vivo specific imaging using the NIR bio-imaging platform of the
      heterogeneous distributed EGF receptors. Moreover, in the adjacent
      gastrointestinal tissue of the same patients, which by Western blotting was
      demonstrated as EGF receptor negative, no labeling with EGF-NIR probe was
      detected. Present results support the concept of tumor imaging by measuring EGF
      receptor levels using EGF-NIR probe. This platform is advantageous for EGF
      receptor bio-imaging of the NCI-60 recommended panel of tumor cell lines
      including 6-9 colorectal cell lines, since it avoids radioactive probes and is
      appropriate for use in the clinical setting using NIR technologies in a real-time
      manner. 

PMID- 23857062
TI  - Cascading cis-cleavage on transcript from trans-acting siRNA-producing locus 3.
AB  - The production of small RNAs (sRNAs) from phased positions set by microRNA
      directed cleavage of trans-acting-siRNA-producing locus (TAS) transcript has been
      characterized extensively; however, the production of sRNAs from non-phased
      positions remains unknown. We report three cis-cleavages that occurred in TAS3
      transcripts in Vitis vinifera, by combining high-throughput sRNA deep sequencing
      information with evolutional conservation and genome-wide RNA degradome analysis.
      The three cis-cleavages can be deciphered to generate an orderly cleavage
      cascade, and can also produce distinct phasing patterns. Each of the patterns,
      either upstream or downstream of the cis-cleaved position, had a set of sRNAs
      arranged in 21-nucleotide increments. Part of the cascading cis-cleavages was
      also conserved in Arabidopsis thaliana. Our results will enhance the
      understanding of the production of sRNAs from non-phased positions that are not
      set by microRNA-directed cleavage. 

PMID- 23857063
TI  - Incidence of female urethral diverticulum: a population-based analysis and
      literature review.
AB  - INTRODUCTION AND HYPOTHESIS: Urethral diverticulum (UD) is a protrusion of the
      urethra through the periurethral fascia. We aimed to determine the population
      based incidence of female UD. METHODS: Using the records-linkage system of the
      Rochester Epidemiology Project (REP), we identified women 18 years and older with
      a new diagnosis of UD in Olmsted County, Minnesota, USA, from 1 January 1980,
      through 31 December 2011. We also identified cases meeting the same criteria
      diagnosed at Mayo Clinic, regardless of county of residency. Incidence rates were
      calculated and trends for changes in incidence over time were tested. We
      conducted a systematic search of the MEDLINE, EMBASE, Cochrane Systematic
      Reviews, CENTRAL, Web of Science, and Scopus databases from inception through 30
      March 2013, to identify published reports of UD incidence or prevalence. RESULTS:
      We identified 164 incidence cases, including 26 women residing in Olmsted County.
      Age-adjusted annual incidence of UD in Olmsted County was 17.9 per 1,000,000
      women (<0.02 %) per year (95 % CI, 10.9-24.9). We observed a trend toward
      increased incidence during the past 3 decades (P = 0.03). In our literature
      review, only 7 studies included an estimate of incidence or prevalence of UD;
      these estimates ranged from 6.4 per 1,000,000 per year (<0.01 %) having surgical
      intervention related to UD to a 4.7 % rate of UD diagnosed in asymptomatic women
      admitted for gynecological or obstetric issues. CONCLUSIONS: In this population
      based study, female UD was a rare disease, affecting fewer than 20 per 1,000,000
      women (<0.02 %) per year.

PMID- 23857064
TI  - Pelvic plexus compression due to a uterine leiomyoma in a woman with acute
      urinary retention: a new hypothesis.
AB  - Acute urinary retention (AUR) in women is an uncommon occurrence described by the
      International Continence Society (ICS) as a painful, palpable, or perceptible
      bladder when the patient is unable to pass urine. Contrarily to men, AUR in women
      is not usually due to any obstructive process. Neurologic causes are the most
      common reason for AUR in reproductive-age women. A few case reports have been
      published concerning women suffering from gynecological pathology and AUR, and
      they propose extrinsic compression of the urinary tract. In the case we report,
      AUR pathophysiology was compression of the pelvic plexus by a giant uterine
      leiomyoma. An electromyogram displayed motor polyradiculopathy of S1 and S2 nerve
      roots, and the patient was unable to urinate due to an uncontractible bladder. 

PMID- 23857065
TI  - Female genital circumcision/mutilation: implications for female urogynaecological
      health.
AB  - "Female genital circumcision" or "female genital mutilation", as it is called
      more often, is an operation that is primarily carried out in Africa. Owing to
      migration, physicians are increasingly confronted with this issue in Western
      countries as well. A range of negative effects may result from this operation and
      this article aims to address consequences for female pelvic health. Special
      emphasis is placed on urogynaecological health consequences; in particular, on
      "voiding difficulties", "recurrent urinary tract infections" and "vesicovaginal
      fistula". All of these occur mostly in infibulated women, i.e. in women whose
      genitalia are sealed by the most severe form of circumcision. Some of the
      problems that may emerge as a result of the operation can be resolved by
      defibulation (i.e. surgical reopening of the sealed vulva). Female genital
      circumcision is a sensitive topic even in the area of research and reliable data
      are therefore scarce. 

PMID- 23857066
TI  - High contrast reflectance imaging of simulated lesions on tooth occlusal surfaces
      at near-IR wavelengths.
AB  - INTRODUCTION: In vivo and in vitro studies have shown that high contrast images
      of tooth demineralization can be acquired in the near-infrared (near-IR) without
      the interference of stain. The purpose of this study is to compare the lesion
      contrast in reflectance at near-IR wavelengths coincident with high water
      absorption with those in the visible, the near-IR at 1,300 nm and with
      fluorescence measurements for early lesions in occlusal surfaces. METHODS: Twenty
      four human molars were used in this in vitro study. Teeth were painted with an
      acid-resistant varnish, leaving a 4 * 4 mm window in the occlusal surface of each
      tooth exposed for demineralization. Artificial lesions were produced in the
      exposed windows after 1- and 2-day exposure to a demineralizing solution at pH
      4.5. Lesions were imaged using near-IR reflectance at three wavelengths, 1,300,
      1,460, and 1,600 nm using a high definition InGaAs camera. Visible light
      reflectance, and fluorescence with 405 nm excitation and detection at wavelengths
      greater than 500 nm were also used to acquire images for comparison. Crossed
      polarizers were used for reflectance measurements to reduce interference from
      specular reflectance. RESULTS: The contrast of both the 1- and 2-day lesions were
      significantly higher (P < 0.05) for near-IR reflectance imaging at 1,460 and
      1,600 nm than it was for near-IR reflectance imaging at 1,300 nm, visible
      reflectance imaging, and fluorescence. CONCLUSION: The markedly higher contrast
      at 1,460 and 1,600 nm wavelengths, coincident with higher water absorption,
      suggest that these wavelengths are better suited than 1,300 nm for imaging
      early/shallow demineralization on tooth surfaces.

PMID- 23857067
TI  - Patch testing for noncontact dermatitis: the atopy patch test for food and
      inhalants.
AB  - The atopy patch test (APT) is defined as a patch test procedure to assess delayed
      type hypersensitivity reactions against those protein allergens known to elicit
      IgE-mediated type I reactions in atopic patients. This patch test procedure uses
      intact protein allergens instead of haptens in an optimized test setting and with
      a special reading key. It may be clinically useful especially for atopic
      dermatitis, as the currently available test procedures either target the wrong
      reaction type (type I and not type IV) or use the wrong allergens (haptens and
      not protein allergen). A positive APT reaction correlates with a positive
      lymphocyte transformation test and allergen-specific Th2 cells in the peripheral
      blood. As even small changes in the test procedure influence the sensitivity,
      specificity, and reproducibility of the APT, the European Task Force on Atopic
      Dermatitis (ETFAD) has developed a standardized APT technique: Intact protein
      allergens, purified in petrolatum, are applied in 12-mm-diameter Finn chambers
      mounted on Scanpor tape for 48 h to non-irritated, non-abraded, or tape-stripped
      skin of the upper back for 48 h; the evaluation of the test reaction is done
      after 48 and 72 h using the ETFAD reading key, assessing erythema as well as
      number and distribution pattern of the papules. The APT may reveal type IV
      sensitization in patients who are negative for the respective type I tests.
      Limited availability of the expensive test substances and limited reimbursement
      is among the factors restricting the routine use of the APT.

PMID- 23857068
TI  - Economic need among older Latinos: applying the Elder Economic Security
      StandardTM Index.
AB  - The first official U.S. federal poverty line was developed in the 1960s; since
      the mid-1990s the scientific consensus has been that it has become outdated and
      inaccurate. This article explains the key elements of the current federal measure
      that are inaccurate for older adults in general and older Latinos specifically.
      An alternative is described that addresses the key failings of the current
      measure. The alternative, the Elder Economic Security StandardTM Index (Elder
      Index), adapts a national methodology to the basic costs of living in California
      for 2007 using data from the American Community Survey, and other public data
      sources. The results show that the amount needed for basic economic security in
      California is higher than the federal poverty level in all counties, and averages
      about twice the federal level. Housing costs are the largest component of costs
      in most counties, although health care is the largest component for couples in
      lower housing cost counties. Among singles and couples age 65 and over in
      California, almost 60% of Latinos have incomes below the Elder Index compared to
      one-quarter of non-Latino whites. The rates are higher among renters, and older
      Latinos are more likely than non-Latino whites to rent. Applying the Elder Index
      in California documents the disproportionate rates of economic insecurity among
      older Latinos. The findings indicate that changes to public programs such as
      Social Security and Medicare that decrease benefits or increase costs will have
      disproportionately negative impact on the ability of most older Latinos to pay
      for basic needs.

PMID- 23857069
TI  - [Cervical vertebroplasty - percutaneous technique of the anterior approach].

PMID- 23857070
TI  - [Dysembryoplastic neuroepithelial tumor (DNET) with pronounced calcinosis].

PMID- 23857071
TI  - [Total hemimegalencephaly].

PMID- 23857072
TI  - A difficult nasogastric tube in a patient with nephrogenic systemic fibrosis.

PMID- 23857073
TI  - Application of a novel metal artifact correction algorithm in flat-panel CT after
      coil embolization of brain aneurysms: intraindividual comparison.
AB  - PURPOSE: To evaluate a novel algorithm for correcting beam hardening artifacts
      caused by metal implants in computed tomography performed on a C-arm angiography
      system equipped with a flat panel (FP-CT). MATERIALS AND METHODS: 16 datasets of
      cerebral FP-CT acquisitions after coil embolization of brain aneurysms in the
      context of acute subarachnoid hemorrhage have been reconstructed by applying a
      soft tissue kernel with and without a novel reconstruction filter for metal
      artifact correction. Image reading was performed in multiplanar reformations
      (MPR) in average mode on a dedicated radiological workplace in comparison to the
      preinterventional native multisection CT (MS-CT) scan serving as the anatomic
      gold standard. Two independent radiologists performed image scoring following a
      defined scale in direct comparison of the image data with and without artifact
      correction. For statistical analysis, a random intercept model was calculated.
      RESULTS: The inter-rater agreement was very high (ICC = 86.3 %). The soft tissue
      image quality and visualization of the CSF spaces at the level of the implants
      was substantially improved. The additional metal artifact correction algorithm
      did not induce impairment of the subjective image quality in any other brain
      regions. CONCLUSION: Adding metal artifact correction to FP-CT in an acute
      postinterventional setting helps to visualize the close vicinity of the aneurysm
      at a generally consistent image quality.

PMID- 23857075
TI  - Music to reduce pain and distress in the pediatric emergency department: a
      randomized clinical trial.
AB  - IMPORTANCE: Many medical procedures aimed at helping children cause them pain and
      distress, which can have long-lasting negative effects. Music is a form of
      distraction that may alleviate some of the pain and distress experienced by
      children while undergoing medical procedures. OBJECTIVE: To compare music with
      standard care to manage pain and distress. DESIGN, SETTING, AND PARTICIPANTS:
      Randomized clinical trial conducted in a pediatric emergency department with
      appropriate sequence generation and adequate allocation concealment from January
      1, 2009, to March 31, 2010. Individuals assessing the primary outcome were blind
      to treatment allocation. A total of 42 children aged 3 to 11 years undergoing
      intravenous placement were included. INTERVENTIONS: Music (recordings selected by
      a music therapist via ambient speakers) vs standard care. MAIN OUTCOMES AND
      MEASURES: The primary outcome was behavioral distress assessed blinded using the
      Observational Scale of Behavioral Distress-Revised. The secondary outcomes
      included child-reported pain, heart rate, parent and health care provider
      satisfaction, ease of performing the procedure, and parental anxiety. RESULTS:
      With or without controlling for potential confounders, we found no significant
      difference in the change in behavioral distress from before the procedure to
      immediately after the procedure. When children who had no distress during the
      procedure were removed from the analysis, there was a significantly less increase
      in distress for the music group (standard care group = 2.2 vs music group = 1.1,
      P < .05). Pain scores among children in the standard care group increased by 2
      points, while they remained the same in the music group (P = .04); the difference
      was considered clinically important. The pattern of parent satisfaction with the
      management of children's pain was different between groups, although not
      statistically significant (P = .07). Health care providers reported that it was
      easier to perform the procedure for children in the music group (76% very easy)
      vs the standard care group (38% very easy) (P = .03). Health care providers were
      more satisfied with the intravenous placement in the music group (86% very
      satisfied) compared with the standard care group (48%) (P = .02). CONCLUSIONS AND
      RELEVANCE: Music may have a positive impact on pain and distress for children
      undergoing intravenous placement. Benefits were also observed for the parents and
      health care providers. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00761033.

PMID- 23857074
TI  - The human impact of tropical cyclones: a historical review of events 1980-2009
      and systematic literature review.
AB  - Background. Cyclones have significantly affected populations in Southeast Asia,
      the Western Pacific, and the Americas over the past quarter of a century. Future
      vulnerability to cyclones will increase due to factors including population
      growth, urbanization, increasing coastal settlement, and global warming. The
      objectives of this review were to describe the impact of cyclones on human
      populations in terms of mortality, injury, and displacement and, to the extent
      possible, identify risk factors associated with these outcomes. This is one of
      five reviews on the human impact of natural disasters. Methods. Data on the
      impact of cyclones were compiled using two methods, a historical review from 1980
      to 2009 of cyclone events from multiple databases and a systematic literature
      review of publications ending in October 2012. Analysis included descriptive
      statistics and bivariate tests for associations between cyclone characteristics
      and mortality using Stata 11.0. Findings. There were 412,644 deaths, 290,654
      injured, and 466.1 million people affected by cyclones between 1980 and 2009, and
      the mortality and injury burden was concentrated in less developed nations of
      Southeast Asia and the Western Pacific. Inconsistent reporting suggests this is
      an underestimate, particularly in terms of the injured and affected populations.
      The primary cause of cyclone-related mortality is drowning; in developed
      countries male gender was associated with increased mortality risk, whereas
      females experienced higher mortality in less developed countries. Conclusions.
      Additional attention to preparedness and early warning, particularly in Asia, can
      lessen the impact of future cyclones. 

PMID- 23857076
TI  - Distinct metabolic differences between various human cancer and primary cells.
AB  - Recent years have seen resurging interest in cancer cell metabolism and the role
      of secreted cancer metabolites in modulating the tumor stroma. Using a
      combination of nontargeted and targeted LC and GC-MS methods, the exometabolomes
      of three leukemia, two melanoma, three renal cell carcinoma, two colorectal
      adenocarcinoma, four hepatocellular carcinoma, three breast cancer, two bladder
      carcinoma, and one glioblastoma cell line, as well as five primary cultures of
      human melanocytes, hepatocytes, monocytes, CD4 and CD8 lymphocytes, that had been
      all cultivated under identical conditions, were investigated. Unsupervised
      affinity propagation clustering of the metabolic footprints yielded five distinct
      clusters that grouped the investigated cell cultures mainly according to the
      tissue of origin. A common expected feature of all neoplastic cells was high
      lactate production. Extracellular arginine and nicotinamide were major
      discriminants between normal and neoplastic hepatocytes. Further, significant
      differences in the assimilation of di- and tripeptides were observed. This
      finding appears to underscore the importance of peptides for meeting the
      increased bioenergetic and biosynthetic demands of many cancers. 

PMID- 23857077
TI  - Surgical treatment of acute pancreatitis.
AB  - BACKGROUND: Acute pancreatitis remains an unpredictable, potentially lethal
      disease with significant morbidity and mortality rates. New insights in the
      pathophysiology of acute pancreatitis have changed management concepts. In the
      first phase, characterized by a systemic inflammatory response syndrome, organ
      failure, not related to infection but rather to severe inflammation, dominates
      the focus of treatment. In the second phase, secondary infectious complications
      largely determine the clinical outcome. As infection is associated with increased
      mortality in acute pancreatitis, numerous prophylactic strategies have been
      explored in the past two decades. PURPOSE: This review describes the strategies
      that have been developed to lower the infection rate, in an attempt to lower
      mortality. Antibiotic prophylaxis has been the subject of many RCT's without
      showing convincing evidence of their efficacy. Probiotics, although theoretically
      capable of lowering the rate of infection, also had no effect on infectious
      complications, and consequently, no effective strategy to lower the rate of
      infectious complications is currently available. In the second part of this
      review, new approaches for necrosectomy that have been designed by different
      centers around the world are discussed. All the interventional techniques have in
      common their aim to lower the invasive character, hypothesizing that lowering the
      surgical trauma will improve survival and lower complication rates. Recent
      advances include postponing intervention as a strategy to facilitate necrosectomy
      and improve prognosis and the "step-up approach" in case of infected necrosis.
      The step-up approach includes percutaneous catheter drainage as the first step,
      to be followed by necrosectomy, either through a minimally invasive approach or
      by open necrosectomy, as the next step. CONCLUSIONS: All attempts to develop
      treatment strategies to lower the infection rate in acute pancreatitis have
      failed. Accumulating evidence is emerging to show that the combination of
      centralization, the use of catheter drainage as the first step of invasive
      treatment, and the development of minimally invasive techniques, improve the
      outlook for patients with infected necrosis. It is uncertain at this point in
      time as to which of the three effects is dominant in the improvement of
      prognosis.

PMID- 23857078
TI  - Network representations and methods for the analysis of chemical and biochemical
      pathways.
AB  - Systems biologists increasingly use network representations to investigate
      biochemical pathways and their dynamic behaviours. In this critical review, we
      discuss four commonly used network representations of chemical and biochemical
      pathways. We illustrate how some of these representations reduce network
      complexity but result in the ambiguous representation of biochemical pathways. We
      also examine the current theoretical approaches available to investigate the
      dynamic behaviour of chemical and biochemical networks. Finally, we describe how
      the critical chemical and biochemical pathways responsible for emergent dynamic
      behaviour can be identified using network mining and functional mapping
      approaches. 

PMID- 23857079
TI  - Phosphorylation of Arabidopsis thaliana MEKK1 via Ca(2+) signaling as a part of
      the cold stress response.
AB  - The Arabidopsis mitogen activated protein kinase kinase kinase (MEKK1) plays an
      important role in stress signaling. However, little is known about the upstream
      pathways of MEKK1. This report describes the regulation of MEKK1 activity during
      cold signaling. Immunoprecipitated MEKK1 from cold-treated Arabidopsis seedlings
      showed elevated kinase activity towards mitogen activated protein kinase kinase2
      (MKK2), one of the candidate MEKK1 substrates. To clarify how MEKK1 becomes
      active in response to cold stress signaling, MEKK1 phosphorylation was monitored
      by an enzyme extracted from the seedlings grown under cold stress with or without
      EGTA. MEKK1 was phosphorylated after cold stress, but EGTA inhibited the
      phosphorylation. MKK2 was also phosphorylated by the same extract, but only when
      EGTA was absent. These results suggested that Ca(2+) signaling occurred upstream
      of the MEKK1-MKK2 pathway. Full-length MEKK1 showed almost no activity but MEKK1
      without the N-terminal region (MEKK1 KD) that retained the kinase domain had a
      strong ability to phosphorylate MKK2, demonstrating the inhibitory role of the N
      terminal region of MEKK1. In addition, MEKK1 was phosphorylated by
      calcium/calmodulin-regulated receptor-like kinase (CRLK1), which suggested that
      CRLK1 is one of candidates located upstream of MEKK1. 

PMID- 23857080
TI  - Phylogeny and chromosomal variations in East Asian Carex, Siderostictae group
      (Cyperaceae), based on DNA sequences and cytological data.
AB  - Carex (Cyperaceae) is one of the largest genera of the flowering plants, and
      comprises more than 2,000 species. In Carex, section Siderostictae with broader
      leaves distributed in East Asia is thought to be an ancestral group. We aimed to
      clarify the phylogenetic relationships and chromosomal variations within the
      section Siderostictae, and to examine the relationship of broad-leaved species of
      the sections Hemiscaposae and Surculosae from East Asia, inferred from DNA
      sequences and cytological data. Our results indicate that a monophyletic
      Siderostictae clade, including the sections Hemiscaposae, Siderostictae and
      Surculosae, as the earliest diverging group in the tribe Cariceae. Low chromosome
      numbers, 2n = 12 or 24, with large sizes were observed in these three sections.
      Our results suggest that the genus Carex might have originated or relictly
      restricted in the East Asia. Geographical distributions of diploid species are
      restricted in narrower areas, while those of tetraploid species are wider in East
      Asia. It is concluded that chromosomal variations in Siderostictae clade may have
      been caused by polyploidization and that tetraploid species may have been able to
      exploit their habitats by polyploidization.

PMID- 23857081
TI  - Pressure safety range of barotrauma with lung recruitment manoeuvres: a
      randomised experimental study in a healthy animal model.
AB  - CONTEXT: Recruitment manoeuvres aim at reversing atelectasis during general
      anaesthesia but are associated with potential risks such as barotrauma.
      OBJECTIVE: To explore the range of pressures that can be used safely to fully
      recruit the lung without causing barotrauma in an ex-vivo healthy lung rabbit
      model. DESIGN: Prospective, randomised, experimental study. SETTING: Experimental
      Unit, La Paz University Hospital, Madrid, Spain. ANIMALS: Fourteen healthy young
      New Zealand rabbits of 12 weeks of age. INTERVENTIONS: Animals were euthanised,
      the thorax and both pleural spaces were opened and the animals were allocated
      randomly into one of two groups submitted to two distinct recruitment manoeuvre
      strategies: PEEP-20 group, in which positive end-expiratory pressure (PEEP) was
      increased in 5-cmH2O steps from 0 to 20 cmH2O and PEEP-50 group, in which PEEP
      was increased in 5-cmH2O steps from 0 to 50 cmH2O. In both groups, a driving
      pressure of 15 cmH2O was maintained until maximal PEEP and its corresponding
      maximal inspiratory pressures (MIPs) were reached. From there on, driving
      pressure was progressively increased in 5-cmH2O steps until detectable barotrauma
      occurred. Two macroscopic conditions were defined: anatomically open lung and
      barotrauma. MAIN OUTCOME MEASURES: We measured open lung and barotrauma MIP, PEEP
      and driving pressure obtained using each strategy. A pressure safety range,
      defined as the difference between barotrauma MIP and anatomically open lung MIP,
      was also determined in both groups. RESULTS: Open lung MIP was similar in both
      groups: 23.6 +/- 3.8 and 23.3 +/- 4.1 cmH2O in the PEEP-50 and PEEP-20 groups,
      respectively (P = 0.91). However, barotrauma MIP in the PEEP-50 group was higher
      (65.7 +/- 3.4 cmH2O) than in the PEEP-20 group (56.7 +/- 5 0.2 cmH2O) (P = 0.003)
      resulting in a safety range of pressures of respectively 33.3 +/- 8.7 and 42.1 +/
      3.9 cmH2O (P = 0.035). CONCLUSION: In this ex-vivo model, we found a substantial
      difference between recruitment and barotrauma pressures using both recruitment
      strategies. However, a higher margin of safety was obtained when a higher PEEP
      and lower driving pressure strategy was used for recruiting the lung.

PMID- 23857082
TI  - Altered incidence of meiotic errors and Down syndrome birth under extreme low
      socioeconomic exposure in the Sundarban area of India.
AB  - We conducted a survey to analyze the genetic epidemiology of trisomy 21 Down
      syndrome births in the Sundarban delta region of India. In this region,
      inhabitants are chiefly from marginalized poor tribal communities and have lived
      in extremely low socioeconomic condition for several generations. Microsatellite
      genotyping revealed an meiosis I/meiosis II ratio that is different from the
      previous reports on the Down syndrome populations from other parts of the world.
      Analyses of distribution of achiasmate nondisjunction at maternal meiosis I in
      interaction with different maternal age groups (young, middle, and old) revealed
      a very concordant pattern to that of urban and semi-urban Down syndrome cases
      previously studied by our group. However, the frequency of achiasmate meiosis is
      much lower, which suggests that extreme low socioeconomic exposure imparts risk
      of chromosomal nondisjunction even when the maternal chromosomes 21 engage in
      proper chiasma formation at prophase I of oogenesis. 

PMID- 23857083
TI  - Hierarchically porous Co3O4 hollow spheres with tunable pore structure and
      enhanced catalytic activity.
AB  - Co3O4 hollow spheres with two-level hierarchical pores and high surface area are
      synthesized, and the shell thickness and the mesoporous structure are well-tuned
      through pre-treatment of the carbon spheres with alkali/acid. Evaluation of the
      Co3O4 hollow spheres for the combustion of CH4 reveals that they exhibit
      excellent catalytic activity and durability. 

PMID- 23857084
TI  - Effects of hepatocellular carcinoma on the survival of patients with primary
      biliary cirrhosis in the era of ursodeoxycholic acid therapy.

PMID- 23857085
TI  - Clinical features of 10 patients with IgG4-related retroperitoneal fibrosis.
AB  - OBJECTIVE: To elucidate the clinical characteristics of IgG4-related
      retroperitoneal fibrosis (RF). METHODS: IgG4-related RF was diagnosed when all of
      the following three criteria were fulfilled: retroperitoneal soft tissue masses
      surrounding the aorta and/or adjacent tissues, elevation of the serum IgG4
      levels, and abundant infiltration of IgG4-positive plasma cells in at least one
      organ or site. Ten patients were diagnosed as having IgG4-related RF. RESULTS:
      The mean age at diagnosis was 70.1 years, and the male-to-female ratio was 1:0.6.
      Only two patients had initial symptoms predominantly related to RF (back pain and
      edema of the lower extremities), while the remaining eight patients reported
      initial symptoms due to associated diseases. On laboratory examination, a severe
      inflammatory reaction was observed in one patient. Elevation of the levels of
      serum IgG and IgE, eosinophilia and positivity of antinuclear antibodies were
      detected in seven, five, two and seven patients, respectively. The
      retroperitoneal masses were detected primarily in the left renal hilus in four
      patients, in the periaortic region in five patients and in both regions in one
      patient. Hydronephrosis was present in five patients. The histological diagnosis
      was confirmed in the retroperitoneal masses (resection, n=1 biopsy, n=2) and
      extraretroperitoneal lesions (n=7). Twenty-four other IgG4-related diseases were
      found to be associated with IgG4-related RF in nine patients (autoimmune
      pancreatitis (n=2), sialadenitis (n=4), dacryoadenitis (n=5), lymphadenopathy
      (n=9), pulmonary pseudotumor (n=1) and pituitary pseudotumor (n=1)). Seven
      patients underwent steroid therapy, all of whom responded well and showed no
      instances relapse. CONCLUSION: IgG4-related RF has several clinical
      characteristic features. Our diagnostic criteria may be helpful in obtaining a
      correct diagnosis.

PMID- 23857086
TI  - Risk factors for survival and the development of hepatocellular carcinoma in
      patients with primary biliary cirrhosis.
AB  - OBJECTIVE: Early diagnosis of hepatocellular carcinoma (HCC) is critical in the
      management of patients with primary biliary cirrhosis (PBC), since the prognosis
      of PBC has improved. The aim of this study was to investigate whether HCC
      development affects the prognosis of PBC and to identify the risk factors for HCC
      in Japanese patients with PBC. METHODS: We compared the survival rates between
      patients with HCC and those without and analyzed the risk factors for HCC
      development in 210 patients with PBC who were followed up for a median period of
      8.5 years. RESULTS: HCC developed during follow-up in 11 patients (5.2%) and was
      diagnosed simultaneously at the time of diagnosis of PBC in five patients (2.4%)
      who were excluded from the analysis. A Kaplan-Meier analysis showed a significant
      difference in overall survival between the patients who did and did not develop
      HCC (p<0.001). A multivariate analysis revealed age (OR: 1.08, 95% confidence
      interval [CI]: 1.03-1.13, p=0.001), the albumin level (OR: 0.24, 95% CI: 0.10
      0.56, p=0.001), the total bilirubin level (OR: 1.60, 95% CI: 1.09-2.36, p=0.017)
      and HCC development (OR: 2.97, 95% CI: 1.24-7.15, p=0.015) to be significant
      prognostic factors and identified only an advanced histological stage (Scheuer's
      classification III or IV, OR: 6.27, 95% CI: 1.80-21.83, p=0.004) to be a risk
      factor associated with HCC. CONCLUSION: HCC development significantly affects the
      survival of patients with PBC, and an advanced histological stage is the only
      risk factor associated with HCC development. These results highlight the
      important role of liver fibrosis in hepatocarcinogenesis in patients with PBC.

PMID- 23857087
TI  - Lipid deposition in various sites of the skeletal muscles and liver exhibits a
      positive correlation with visceral fat accumulation in middle-aged Japanese men
      with metabolic syndrome.
AB  - Objective In addition to excess visceral fat, lipid deposition in the liver and
      skeletal muscle has been implicated in the pathophysiology of type 2 diabetes and
      metabolic syndrome. This study was designed to explore the relationship between
      hepatic and muscular lipid deposition and visceral fat accumulation in 105 middle
      aged men with metabolic syndrome. Methods Abdominal computed tomography (CT) was
      used to simultaneously evaluate the visceral fat area (VFA) and CT Hounsfield
      unit (HU) values of three different portions of skeletal muscle and the liver.
      Results A significant inverse correlation was observed between the VFA and the CT
      HU values of the iliopsoas muscle, back muscle, rectus abdominis muscle and
      liver. Three types of interventions, i.e., lifestyle modification and treatment
      with antidiabetic drugs, such as Pioglitazone or Miglitol, caused significant
      decreases in visceral fat accumulation. The extent of lipid deposition in the
      liver was strongly correlated with the levels of glucose-lipid metabolic markers,
      which decreased significantly following Pioglitazone treatment. On the other
      hand, the amount of lipid deposition in the three skeletal muscles and the liver
      did not decrease after Miglitol treatment. Conclusion Visceral fat accumulation
      is accompanied by excess lipid deposition in skeletal muscle and the liver in
      patients with metabolic syndrome. The CT-based simultaneous, concise evaluations
      of ectopic lipid deposition and visceral fat mass used in the present study may
      provide unique information for assessing cardiometabolic risks and the
      therapeutic impact in patients with diabetes-obesity syndrome. 

PMID- 23857088
TI  - Clinical and laboratory factors in the differential diagnosis of tuberculous and
      cryptococcal meningitis in adult HIV-negative patients.
AB  - Objective It is difficult to make the differential diagnosis between tuberculous
      meningitis (TBM) and cryptococcal meningitis (CM) when the smear is negative. The
      objective of this study was to create a diagnostic rule for differentiating TBM
      from CM in adult HIV-negative patients based on clinical and laboratory features.
      Methods The clinical and laboratory data of 219 adult HIV-negative patients
      satisfying the diagnostic criteria for tuberculous (n=100) and cryptococcal
      (n=119) meningitis hospitalized at the Third Affiliated Hospital of Sun Yat-Sen
      University during the period 2000-2009 were retrospectively analyzed. Features
      found to be independently predictive of tuberculous meningitis were modeled using
      a multivariate logistic regression to create a diagnostic rule. The performance
      of the diagnostic rule was assessed using a prospective test data method. Results
      Six factors were found to be predictive of a diagnosis of tuberculous meningitis:
      gender, mental disorders, vision and/or hearing damage, proteins in the
      cerebrospinal fluid, the total cerebrospinal fluid white cell count and the
      coexistence of tuberculosis in peripheral organs. The diagnostic rule developed
      using these features exhibited 78.0% sensitivity, 95.2% specificity, 92.9%
      positive predictive value and 84.4% negative predictive value. The corresponding
      values for the diagnostic rule were 70.0% and 88.0% using prospective test data.
      Conclusion Clinical and laboratory features can be helpful in the differential
      diagnosis of tuberculous meningitis and cryptococcal meningitis in adult HIV
      negative patients. 

PMID- 23857089
TI  - Duodenocolic fistula caused by a peptic stomal ulcer following distal
      gastrectomy.
AB  - We herein describe the case of a 51-year-old man with a duodenocolic fistula
      (DCF) caused by a stomal ulcer. The patient complained of watery diarrhea,
      dysgeusia and malnutrition. His medical history included distal gastrectomy with
      Billroth I reconstruction for duodenal ulcer perforation. A combination study
      using endoscopy and contrast imaging confirmed the presence of DCF. Laparotomic
      fistulectomy was performed, which resulted in the patient's recovery from
      diarrhea and malnutrition. The histological findings suggested that the fistula
      had originated from a stomal ulcer. In patients with chronic watery diarrhea of
      obscure origin following gastrectomy, DCF is a possible cause of the diarrhea. 

PMID- 23857090
TI  - Long-term follow-up of gastric adenocarcinoma with chief cell differentiation
      using upper gastrointestinal tract endoscopy.
AB  - During upper endoscopic screening, a 71-year-old asymptomatic woman was found to
      have a small, yellowish, superficial elevated lesion in the upper third of her
      stomach, without any signs of atrophic mucosa. The patient underwent endoscopic
      follow-up once a year for approximately five years; however, changes in the tumor
      were barely detectable. Endoscopic mucosal resection was performed, and a
      histological examination confirmed the diagnosis of gastric adenocarcinoma with
      chief cell differentiation (GA-CCD). GA-CCD is rare; therefore, its
      clinicopathological features remain unknown. This case suggests that only barely
      detectable endoscopic changes may be observed in GA-CCD during long-term follow
      up. 

PMID- 23857091
TI  - A complete response induced by 21-day sorafenib therapy in a patient with
      advanced hepatocellular carcinoma.
AB  - The response rate and overall survival after sorafenib administration in patients
      with advanced hepatocellular carcinoma are unsatisfactory. We herein present the
      case of a 65-year-old man with multiple lung metastases of hepatocellular
      carcinoma. Because the patient had liver cirrhosis of Child-Pugh B accompanied by
      pancytopenia, sorafenib administration was initiated at a dose of 400 mg daily.
      Although he received sorafenib for only 21 days, the patient exhibited complete
      regression of the tumors. There was no clinical evidence of recurrence without
      the administration of anticancer treatment. It is unique that short-term
      sorafenib treatment achieved a complete response. 

PMID- 23857092
TI  - Papillary thyroid carcinoma recurring as squamous cell carcinoma 10 years after
      total thyroidectomy: lessons from rapidly progressive papillary thyroid
      carcinoma.
AB  - Primary squamous cell carcinoma (SCC) of the thyroid is very rare. There are no
      reports of metastatic papillary thyroid carcinoma (PTC) converting to SCC in
      cervical lymph nodes following total thyroidectomy due to conventional PTC. An 86
      year-old woman with a remote history of total thyroidectomy due to PTC underwent
      palliative neck surgery to treat recurrent bleeding originating from a metastatic
      tumor of the cervical lymph nodes. The resected mass was composed of mixed SCC
      and PTC. Although primary SCC rarely occurs in the thyroid, conversion of PTC to
      SCC should be suspected if preexisting PTC exhibits highly aggressive behavior. 

PMID- 23857093
TI  - von Hippel Lindau disease with colon adenocarcinoma, renal cell carcinoma and
      adrenal pheochromocytoma.
AB  - von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome
      characterized by the presence of heterogeneous tumors derived from different
      organs. VHL is caused by germline mutations in the VHL tumor suppressor gene
      located on chromosome 3p25-26. The loss of functional VHL protein contributes to
      tumorigenesis. VHL tumors are most frequently derived from the kidneys, adrenal
      gland, central nervous system, eyes, inner ear, epididymis and pancreas. We
      herein describe the case of a 64-year-old man carrying the VHL gene mutation
      affected by simultaneous colon adenocarcinoma, renal clear cell carcinoma and
      adrenal pheochromocytoma.

PMID- 23857094
TI  - Successful delivery in a patient with antineutrophil cytoplasmic antibody
      associated glomerulonephritis.
AB  - We herein report a case of spontaneous pregnancy and preterm delivery in a 29
      year-old patient with myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA)
      associated glomerulonephritis. Her basal serum creatinine level before pregnancy
      was 1.4 mg/dL and her urinary protein level was approximately 2 g/day. The
      proteinuria and hematuria increased during pregnancy, and the patient was
      admitted to our hospital and treated with prednisolone (PSL). At 27 weeks of
      gestation, she delivered a live infant weighing 848 g via cesarean section. No
      relapse of ANCA-associated glomerulonephritis occurred. 

PMID- 23857096
TI  - Nonbacterial thrombotic endocarditis leading to acute heart failure due to aortic
      stenosis in a patient with lung cancer.
AB  - We herein report an autopsied case of a patient with adenocarcinoma of the lungs
      who developed nonbacterial thrombotic endocarditis (NBTE) that caused acute heart
      failure (AHF) due to acute aortic stenosis (AS). A 37-year-old man was admitted
      to our hospital due to chest pain and fever. He was diagnosed as having Stage IV
      lung cancer. Following the administration of chemotherapy, the patient presented
      with acute onset of dyspnea. He was diagnosed with having AHF based on his
      clinical course and physical findings, and ultimately he died without responding
      to treatment. The autopsy revealed that NBTE caused acute AS leading to AHF. 

PMID- 23857095
TI  - Castleman's disease accompanied by hypolipidemic cerebral hemorrhage and
      nephrosclerosis.
AB  - A 56-year-old Japanese man developed a cerebral hemorrhage and was diagnosed with
      plasma cell-type multicentric Castleman's disease (MCD) based on the findings of
      an inguinal lymph node biopsy in addition to clinical findings, including
      hypergammaglobulinemia, anemia and elevation of the levels of CRP and serum IL-6.
      Although a renal biopsy showed nephrosclerosis, the levels of serum lipids and
      apolipoprotein were low. Following the initiation of treatment with anti
      interleukin-6 receptor antibodies, the hypergammaglobulinemia, anemia, CRP level
      and serum lipid profile improved. However, inflammation due to overproduction of
      IL-6 persisted, and atherosclerotic vascular events occurred as critical
      complications, even though the serum levels of lipids were very low. 

PMID- 23857097
TI  - Steroid-induced paraparesis: spinal epidural lipomatosis complicated by a wedge
      deformity of the middle thoracic vertebrae.
AB  - Steroid therapy is commonly prescribed, although a variety of complications have
      been reported. Among such complications, spinal epidural lipomatosis is rare and
      difficult to diagnose before paraparesis occurs. The purpose of this report is to
      present a rare but catastrophic complication of steroid therapy. A 64-year-old
      woman undergoing long-term steroid therapy suffered from an osteoporotic
      vertebral compression fracture and was unable to walk due to paraparesis.
      Magnetic resonance imaging (MRI) demonstrated a D7 compression fracture and
      stored epidural adipose tissue between D5 and D8. After surgery, the patient was
      able to walk with double canes. This case indicates that long-term steroid use
      has the potential to induce paraparesis. 

PMID- 23857098
TI  - Bilateral symmetrical pallidal lesions following severe anemia associated with
      gastrointestinal hemorrhage: report of two cases.
AB  - We herein report the cases of two patients with bilateral symmetrical pallidal
      lesions mimicking hypoxic encephalopathy following severe anemia associated with
      gastrointestinal hemorrhage despite a lack of carbon monoxide intoxication.
      Although severe anemia can theoretically result in anemic hypoxia, vulnerable
      pallidal lesions have rarely been described in anemic patients. Interestingly,
      both patients shared common conditions associated with atherosclerosis, including
      heavy smoking, hypertension, type 2 diabetes mellitus and a history of coronary
      artery bypass grafting for ischemic heart disease. Anemic hypoxia may cause
      pallidal involvement in atherosclerotic patients with multiple risk factors. 

PMID- 23857099
TI  - Identification of a novel homozygous SPG7 mutation in a Japanese patient with
      spastic ataxia: making an efficient diagnosis using exome sequencing for
      autosomal recessive cerebellar ataxia and spastic paraplegia.
AB  - Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic
      paraplegias are clinically and genetically heterogeneous disorders with diverse
      neurological and non-neurological features. We herein describe a Japanese patient
      with a slowly progressive form of ataxia and spastic paraplegia. Using whole
      exome sequencing, we identified a novel homozygous frameshift mutation in SPG7,
      encoding paraplegin, in this patient. This is the first report of an SPG7
      mutation in the Japanese population. For disorders previously undetected in a
      particular population, or unrecognized/atypical phenotypes, exome sequencing may
      facilitate molecular diagnosis. 

PMID- 23857100
TI  - Fatal diarrheal disease caused by Vibrio cholerae O67 in a patient with
      myelodysplastic syndrome.
AB  - A 71-year-old man with myelodysplastic syndrome (MDS) receiving treatment with
      azacitidine developed extensive watery diarrhea for three consecutive days. As a
      result of high-grade dehydration, the patient was urgently admitted to the
      hospital and fluid replacement therapy was initiated. However, the patient's
      diarrhea did not improve. Vibrio cholerae non-O1/non-O139 was detected in a fecal
      culture. On the fourth day, the patient died due to circulatory collapse. An
      autopsy revealed extensive necrosis of the intestinal mucosa. Vibrio cholerae non
      O1/non-O139-induced diarrheal disease often develops in patients with hepatic
      cirrhosis and has a serious clinical course. We herein report a fatal outcome of
      Vibrio cholerae O67 infection in an immunocompromised MDS patient. 

PMID- 23857101
TI  - Septic arthritis subsequent to urosepsis caused by hypermucoviscous Klebsiella
      pneumoniae.
AB  - We herein report the first case of septic arthritis caused by rmpA-positive
      hypermucoviscous community-acquired K. pneumoniae that followed urosepsis in a 65
      year-old Japanese woman. The patient responded well to drainage of the abscesses
      and treatment with cefazolin. Although this virulent phenotype of K. pneumoniae
      has been primarily reported in Hong Kong, we confirmed that 18/50 isolates
      obtained in our hospital over the past five years displayed the hypermucoviscous
      phenotype. Therefore, clinicians should consider the possibility of an increasing
      prevalence of rmpA-positive hypermucoviscous K. pneumoniae infection in Japan and
      be particularly vigilant for invasive clinical manifestations, even in patients
      with urinary tract infections. 

PMID- 23857102
TI  - Esophageal impact of shrimp tails.

PMID- 23857103
TI  - Idiopathic gastric volvulus in an adult.

PMID- 23857104
TI  - Aortic dissection induced by a myocardial infarction.

PMID- 23857105
TI  - Apical aneurysm in a patient with hypertrophic cardiomyopathy and midventricular
      obstruction.

PMID- 23857106
TI  - Double scimitar signs.

PMID- 23857107
TI  - Staphylococcal septic emboli in an injection drug user.

PMID- 23857108
TI  - ST-segment elevation in V1-V3 in patients with inferior STEMI: an important sign
      of right ventricular infarction.

PMID- 23857109
TI  - ST-segment elevation in V1-V3 in patients with inferior STEMI: an important sign
      of right ventricular infarction (reply).

PMID- 23857112
TI  - Bioactive compounds offered in microcapsules to determine the nutritional value
      of copepods' natural diet.
AB  - Experiments were performed, feeding Calanus pacificus seston and a food
      consisting of seston and microcapsules (MU-caps), i.e., protein and lipid MU-caps
      to test for potential biochemical limitation. Seston was collected off Scripps
      Pier (La Jolla, CA, USA). Whereas protein MU-caps were too small to be
      efficiently ingested, lipid MU-caps rich in omega3-highly-unsaturated fatty acids
      (omega3-HUFA) were ingested similarly to natural seston and lipids were
      assimilated. However, egg production experiments exhibited that animals fed with
      lipid MU-caps didn't produce significantly more eggs than with seston of equal
      carbon concentration and egg production even declined when the diet consisted of
      50% lipid MU-caps. Thus, the content of certain omega3-HUFA seemed to have been
      sufficiently high in seston to prevent limitation. Algal counts revealed that
      seston consisted mainly of plankton rich in those fatty acids, such as
      cryptophytes, dinoflagellates, diatoms, and ciliates in the edible size range.
      This might be characteristic for upwelling systems like the area off Southern
      California which are known for high trophic transfer efficiency. 

PMID- 23857110
TI  - Structure of fucoidan from brown seaweed Turbinaria ornata as studied by
      electrospray ionization mass spectrometry (ESIMS) and small angle X-ray
      scattering (SAXS) techniques.
AB  - The purpose of this study is to elucidate both the chemical and conformational
      structure of an unfractionated fucoidan extracted from brown seaweed Turbinaria
      ornata collected at Nha-trang bay, Vietnam. Electrospray ionization mass
      spectrometry (ESI-MS) was used for determining the chemical structure and small
      angle X-ray scattering (SAXS) provided conformational of the structure at the
      molecular level. The results showed that the fucoidan has a sulfate content of
      25.6% and is mainly composed of fucose and galactose residues (Fuc:Gal ~ 3:1).
      ESIMS analysis suggested that the fucoidan has a backbone of 3-linked alpha-l
      Fucp residues with branches, ->4)-Galp(1-> at C-4 of the fucan chain. Sulfate
      groups are attached mostly at C-2 and sometimes at C-4 of both fucose and
      galactose residues. A molecular model of the fucoidan was built based on obtained
      chemical structure and scattering curves estimated from molecular model and
      observed SAXS measurement were fitted. The results indicated that fucoidan under
      study has a rod-like bulky chain conformation. 

PMID- 23857111
TI  - Influence of fucoidans on hemostatic system.
AB  - Three structurally different fucoidans from the brown seaweeds Saccharina
      latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two
      chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and
      a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were
      assessed on anticoagulant and antithrombotic activities in different in vitro
      experiments. The effects were shown to depend on the structural features of the
      compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was
      found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate
      activity, while the polysaccharide CO (DS 0.4) was inactive in all performed
      experiments, even at high concentrations. Additional introduction of sulfate
      groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S,
      while sulfation of CO, giving rise to the preparation CO-S, increased the
      activity dramatically. The high level of anticoagulant activity of
      polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary
      complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin.
      Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect,
      determined mainly by the interaction of OS with the factor Xa in the presence of
      ATIII. Comparable tendencies were observed in the antithrombotic properties of
      the compounds tested. 

PMID- 23857114
TI  - Near-IR phosphorescent metalloporphyrin as a photochemical upconversion
      sensitizer.
AB  - The phosphorescent metalloporphyrin sensitizer PtTPTNP (TPTNP =
      tetraphenyltetranaphtho[2,3]porphyrin) has been successfully coupled with
      perylenediimide (PDI) or rubrene utilized as triplet acceptors/annihilators to
      upconvert 690 nm incident photons into yellow fluorescence through sensitized
      triplet-triplet annihilation at overall efficiencies in the 6-7% range while
      exhibiting exceptional photostability. 

PMID- 23857113
TI  - Brain neuronal activation induced by flibanserin treatment in female rats.
AB  - RATIONALE: Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is developed for
      the treatment of hypoactive sexual desire disorder in women, and its efficacy has
      been evidenced in several clinical studies. Flibanserin prosexual effects have
      been also evidenced in preclinical animal models. However, the mechanism of
      action of flibanserin remains not fully understood. OBJECTIVE: The aim of the
      present study was to examine brain neuronal activation in female rats treated
      with flibanserin, using single immunocytochemical labeling of Fos protein, a
      marker of neuronal activation, and co-localization of Fos and catecholaminergic
      marker. METHOD: Six groups of female rats received either acute or chronic
      administrations of vehicle, flibanserin 15 mg/kg or flibanserin 45 mg/kg. The
      brains were collected and processed for immunocytochemical labeling. RESULTS:
      Acute flibanserin increased levels of Fos immunoreactivity in the nucleus
      accumbens, arcuate hypothalamic nucleus, locus coeruleus, lateral
      paragigantocellular nucleus, and nucleus of the solitary tract. Chronic 22-day
      treatment with flibanserin increased Fos expression in the medial preoptic area
      and arcuate nucleus of the hypothalamus, ventral tegmental area, locus coeruleus,
      and lateral paragigantocellular nucleus. Both acute and chronic flibanserin
      increased the density of activated catecholaminergic neurons in the ventral
      tegmental area but not in the locus coeruleus. CONCLUSION: Altogether, our
      results showed that flibanserin, at the dose known to enhance female sexual
      motivation, preferentially activated the brain regions belonging to the
      mesolimbic dopaminergic pathway and hypothalamic structures involved in the
      integration of sexual cues related to sexual motivation.

PMID- 23857115
TI  - Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by
      inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects.
AB  - Dihydrodiol dehydrogenase (DDH) is frequently detected in cancer cells, and its
      overexpression correlates with drug resistance, the downregulation of DNA repair
      mechanisms, increased frequency of tumor recurrence, cancer cell metastasis and
      poor prognosis. The silencing of DDH expression using siRNA, on the other hand,
      reduces drug resistance and cancer cell mobility. These data suggest that DDH may
      be an oncogene-related protein. However, no specific DDH inhibitor has been
      identified to date. Thus, in this study, we used DDH as a target enzyme in a live
      cell enzyme-linked immunosorbent assay to screen Chinese medicinal herb extracts
      (CMHEs) with the aim of identifying a DDH inhibitor. Using this method, we found
      49 among 796 CMHEs that inhibited DDH expression. We selected three potential
      extracts, which had the highest activity against DDH, for further fractionation
      using high-performance liquid chromatography. The active ingredient was
      identified by immunoblot analysis. The function of the active ingredient was
      characterized by cell function analysis. Our results revealed that the CMHE
      purified compounds targeted DDH, inducing autophagy and reducing DNA repair,
      which in turn enhanced the cytotoxic effects of the anticancer drugs and
      irradiation. 

PMID- 23857116
TI  - Endoscopic management of benign biliary strictures.
AB  - The majority of recent studies of benign biliary strictures (BBSs) have reported
      on treatment of stenotic injuries following cholecystectomy, orthotopic liver
      transplantation, living donor liver transplantation, chronic pancreatitis, and
      different inflammatory conditions such as common bile-duct-related strictures.
      Information about previous surgical procedures is very important for making a BBS
      diagnosis. Diagnostic tools for indeterminate strictures have increased to
      include (1) highly specialized cytological techniques such as fluorescence in
      situ hybridization, (2) cholangioscopy, and (3) endoscopic ultrasound with fine
      needle aspiration (FNA) and intraductal ultrasound. Magnetic resonance
      cholangiopancreatography before endoscopic retrograde cholangiopancreatography
      (ERCP) usually provides an adequate map to plan the endoscopic therapy. After
      traversing the stricture with a guidewire and, occasionally, performing balloon
      dilatation, plastic stents continue to be the basic endotherapy, trying to insert
      the maximum possible number, with an exchange every 3 months during a 12-month
      period. Progressive stenting requires a median number of five ERCPs; therefore,
      it is technically demanding and burdensome but has an average of 80% long-term
      durable stricture dilation. For not-hilar BBS, fully covered self-expanding metal
      stents (FCSEMSs) are emerging as a promising therapy needing fewer of the
      endoscopist's technical skills and reducing ERCP procedures and, probably, costs.
      To equal a 10-mm diameter provided by a single FCSEMS, about three plastic stents
      placed side-by-side are needed. Manufacturers are working to improve FCSEMS
      designs to reduce migration rate and to allow an easy extraction after several
      months in place. Many studies have tried to show reproducible protocols for the
      duration of FCSEMS therapy and the results in different types of BBSs.

PMID- 23857117
TI  - Recent developments in Hirschsprung's-associated enterocolitis.
AB  - Hirschsprung's-associated enterocolitis (HAEC) continues to be a significant
      source of morbidity for patients with Hirschsprung's disease (HD). New clinical
      and histologic classification systems for HAEC will improve consistency between
      reports and increase the ability to compare outcomes. A complete understanding of
      disease pathogenesis is lacking, but evidence suggests that the intestinal
      microbiota may play a role in the development of HD and HAEC. The benefits of
      adjunctive therapies, such as anal dilations and botulinum toxin to reduce the
      incidence of HAEC following corrective endorectal pull-through, remain
      controversial. Finally, new clinical data have identified an association between
      HAEC and inflammatory bowel disease and will likely lead to further genetic
      studies to elucidate the connection between these two disease processes. 

PMID- 23857118
TI  - Comments on 'over-expression of circadian clock gene Bmal1 affects proliferation
      and the canonical Wnt pathway in NIH-3T3 cells'.

PMID- 23857119
TI  - Distinctively higher plasma G72 protein levels in patients with schizophrenia
      than in healthy individuals.

PMID- 23857121
TI  - Antimicrobial stewardship in pediatrics: how every pediatrician can be a steward.
AB  - Antimicrobial stewardship (AS) programs are effective in improving clinical
      outcomes associated with antimicrobial therapies while improving patient safety
      by reducing adverse events and development of bacterial resistance. Understanding
      the basic principles of AS is essential to the successful development and
      implementation of AS strategies. Identifying and developing strategies to address
      barriers and challenges to AS can facilitate the establishment of financial,
      administrative, and organizational support, and agreement and participation by
      individual prescribers. Review of published outcomes of AS demonstrates the
      effectiveness in reducing unnecessary antimicrobial use and adverse events such
      as Clostridium difficile infections. We also illustrate the need for further
      research and expansion of AS activities to office-based practices and communities
      by using novel and innovative AS strategies and by influencing regional and
      national policies. 

PMID- 23857120
TI  - ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.
AB  - To identify loci associated with Alzheimer disease, we conducted a three-stage
      analysis using existing genome-wide association studies (GWAS) and genotyping in
      a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at
      P<0.001) in a previously reported GWAS of seven independent studies (8082
      Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II
      these were examined in an in silico analysis within the Cohorts for Heart and
      Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904
      controls). Six novel signals reaching P<5 * 10(-6) were genotyped in an
      independent Stage III sample (the Fundacio ACE data set) of 2200 sporadic AD
      patients and 2301 controls. We identified a novel association with AD in the
      adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0
      (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2)
      locus, which reached genome-wide significance in the combined discovery and
      genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 * 10(-7) in discovery
      and OR=1.43, P=0.004 in Fundacio ACE data set; combined OR=1.53, P=4.7 * 10(-9)).
      This ATP5H/KCTD2 locus has an important function in mitochondrial energy
      production and neuronal hyperpolarization during cellular stress conditions, such
      as hypoxia or glucose deprivation. 

PMID- 23857122
TI  - Giant retroperitoneal leiomyoma: a case report and review of the literature.
AB  - Retroperitoneal leiomyomata are infrequent, and their prevalence among primary
      retroperitoneal tumours has been estimated as 0.5-1.2%. The authors report a case
      of symptomatic retroperitoneal leiomyoma with a favourable prognosis. A 53-year
      old woman presented for abdominal pain associated to an inflammatory syndrome. A
      contrast-enhanced computed tomography revealed a large abdominopelvic mass and
      patient underwent open surgical excision. Definitive diagnosis was done after
      immunohistochemical assessment. Immunoreactivity was strong for smooth muscular
      actin. Presence of oestrogen and progesterone receptor proteins was also
      detected. Prognosis of these well-differentiated smooth muscle tumours is
      generally favourable but a postoperative surveillance is always recommended. KEY
      WORDS: Leiomyoma, Retroperitoneal space, Surgery.

PMID- 23857123
TI  - Caregiver reported oral health-related quality of life in young American Indian
      children.
AB  - American Indian/Alaska Native (AI/AN) children experience high rates of dental
      decay, yet their pediatric oral health-related quality of life (POQL) has not
      been described. We measured POQL in AI children and compared it in children with
      reported excellent/very good/good versus fair/poor oral health status (OHS) and
      assessed association of OHS, child's age, dental service utilization, and dental
      insurance on POQL scores. Caregivers of 143 AI (100 %), young (mean age 25.1
      months) children reported their POQL score as 4.2 (scale 0-100, lower score
      indicates better POQL); OHS as excellent (35 %), very good (27 %), good (21 %),
      fair (14 %), and poor (3 %); and utilization of urgent dental services (12 %).
      Worse POQL was associated with worse OHS (p = 0.01). After adjustment, worse POQL
      was associated with increased reported use of urgent dental services (p = 0.004).
      POQL of young AI children was generally favorable but worsened with increased
      utilization of urgent dental services.

PMID- 23857124
TI  - Exploratory investigation of plasma metabolomics in human lung adenocarcinoma.
AB  - Globally lung cancer is common among males and recently also noted with
      increasing incidences in females, especially adenocarcinoma. Further, most lung
      cancers are not easily detected until the late stage. Metabolic profiling of
      plasma low molecular weight metabolites may help unveil the complex
      pathophysiological changes during early lung adenocarcinoma development. Here we
      used a combination of gas chromatography-mass spectrometry (GC-MS) and liquid
      chromatography-mass spectrometry (LC-MS) methods to investigate the metabolic
      signatures in the plasma of 31 stage I human lung adenocarcinoma patients and 28
      healthy controls. The metabolic profiles were assayed using orthogonal
      projections to latent structures discriminant analysis (OPLS-DA), and were
      further analyzed to identify the associated marker metabolites. The OPLS-DA
      models derived from both GC-MS and LC-MS showed significant discriminations in
      metabolic profiles between cases and healthy controls. It was found that around
      37 metabolites contributed to the differences. The alterations of these
      metabolites implied disturbances in amino acids, lipids, fatty acids and
      glutaminolysis metabolism in human lung adenocarcinoma, even after removal of
      influencing factors such as age, gender and smoking habits. Of particular
      interest, the sex hormone metabolic pathway involving the sulfate conjugate of
      testosterone, androsterone and pregnenolone was found to be disturbed
      considerably. All these metabolic perturbations occur at an early stage of lung
      adenocarcinoma and thus could act as biomarkers for its early diagnosis. These
      exploratory findings suggest that integration of two sensitive and complementary
      metabolomic approaches enables a comprehensive metabolite profiling for human
      lung adenocarcinoma, although a more extensive study is needed to confirm the
      findings. 

PMID- 23857125
TI  - Rapid identification of human SNAP-25 transcript variants by a miniaturized
      capillary electrophoresis system.
AB  - The 25 kDa synaptosomal-associated protein (SNAP-25) is a crucial component of
      the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex
      and plays an important role in neurotransmission in the central nervous system.
      SNAP-25 has two different splice variants, SNAP-25a and SNAP-25b, differing in
      nine amino acids that results in a slight functional alteration of the generated
      soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex.
      Two independent techniques, a PCR-miniaturized CE method and a real-time PCR
      based approach were elaborated for the specific and quantitative detection of the
      two SNAP-25 transcription variants. DNA-constructs coding for the two isoforms
      were used for optimization. Excellent specificity was observed with the use of
      our previously described highly sensitive miniaturized CE system in combination
      with quantitative PCR. The ratio of the two isoforms were reliably detected in a
      range of at least four orders of magnitude with a linear regression of R(2) =
      0.987. Expression of the two isoforms was determined in human samples, where SNAP
      25 was detected even in non-neural tissues, although at approximately a 100-fold
      lower level compared to the central nervous system. The relative amount of the
      SNAP-25b isoform was higher in the brain, whereas expression of SNAP-25a variant
      proved to be slightly higher in extra-neural cell types. The genomics approach in
      conjunction with the miniaturized CE system introduced in this paper is readily
      applicable for rapid alternative splice variant analysis. 

PMID- 23857126
TI  - The application of transient-state kinetic isotope effects to the resolution of
      mechanisms of enzyme-catalyzed reactions.
AB  - Much of our understanding of the mechanisms of enzyme-catalyzed reactions is
      based on steady-state kinetic studies. Experimentally, this approach depends
      solely on the measurement of rates of free product appearance (d[P]/dt), a
      mechanistically and mathematically complex entity. Despite the ambiguity of this
      observed parameter, the method's success is due in part to the elaborate
      rigorously derived algebraic theory on which it is based. Transient-state
      kinetics, on the other hand, despite its ability to observe the formation of
      intermediate steps in real time, has contributed relatively little to the subject
      due in, some measure, to the lack of such a solid mathematical basis. Here we
      discuss the current state of existing transient-state theory and the difficulties
      in its realistic application to experimental data. We describe a basic analytic
      theory of transient-state kinetic isotope effects in the form of three novel
      fundamental rules. These rules are adequate to define an extended mechanism,
      locating the isotope-sensitive step and identifying missing steps from
      experimental data. We demonstrate the application of these rules to resolved
      component time courses of the phenylalanine dehydrogenase reaction, extending the
      previously known reaction by one new prehydride transfer step and two new post
      hydride transfer steps. We conclude with an assessment of future directions in
      this area. 

PMID- 23857127
TI  - Studies toward the first stereoselective total synthesis of (+/-)-quinolizidine
      195C and other transformations.
AB  - Starting from a thio-substituted 4-quinolizidinone, a series of C-6 alkylated
      derivatives with a trans C-6, C-9a relationship was synthesized. Further
      transformations led to the first stereoselective total synthesis of the structure
      proposed for (+/-)-quinolizidine 195C, the major alkaloid isolated from the skin
      extracts of the Madagascan frog Mantella betsileo. Since the spectral data of the
      synthetic and natural products differed significantly, the true structure of (+/
      )-quinolizidine 195C remains uncertain. 

PMID- 23857128
TI  - The pharmacological activities of (-)-anonaine.
AB  - Several species of Magnoliaceae and Annonaceae are used in Traditional Chinese
      Medicine. (-)-Anonaine, isolated from several species of Magnoliaceae and
      Annonaceae, presents antiplasmodial, antibacterial, antifungal, antioxidation,
      anticancer, antidepression, and vasorelaxant activity. This article provides an
      overview of the pharmacological functions of (-)-anonaine. 

PMID- 23857129
TI  - Osteoarthritis: Osteoporotic OA: a reasonable target for bone-acting agents.
AB  - Beneficial effects of bone-acting drugs in osteoarthritis (OA) are increasingly
      reported, but reliable conclusions regarding their efficacy are hindered by
      methodological drawbacks in study design. Identifying patients with osteoporotic
      OA, a phenotype defined by decreased density associated with high remodelling in
      subchondral bone, might improve the success of bone-directed agents.

PMID- 23857131
TI  - Therapy: Targeting IFN-beta to inflamed joints in arthritic mice.

PMID- 23857132
TI  - Spondyloarthropathies: Ligand-receptor interactions implicated in pathogenesis.

PMID- 23857130
TI  - Advances in understanding the pathogenesis of primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a prototypic autoimmune disorder, management
      of which has long suffered from a lack of knowledge of the underlying
      pathophysiological mechanisms; however, over the past decade major advances have
      been made in understanding the pathogenesis of pSS. The innate immune system has
      been demonstrated to have an important role at the early stage of the disease,
      notably through activation of the type I interferon (IFN) system. In addition,
      mechanisms of B-cell activation in pSS have become clearer, particularly owing to
      recognition of the involvement of the TNF family cytokine B-cell-activating
      factor, production of which is highly dependent on expression of type I and type
      II IFNs. Moreover, key inroads have been made in understanding lymphomagenesis,
      the most severe complication of pSS. IL-12 production and subsequent T-cell
      activation, mainly IFN-gamma-secreting type 1 T-helper cells, have also been
      implicated in disease pathogenesis. Furthermore, evidence implicates
      neuroendocrine system dysfunction in pSS pathogenesis. These pathophysiological
      advances open new avenues of investigation. Indeed, the increased understanding
      of pSS pathogenesis has already led to the development of promising novel
      therapeutic strategies. This article summarizes recent findings regarding the
      pathogenic mechanisms involved in pSS and their implications. 

PMID- 23857133
TI  - [Surgical abdomen caused by traditional treatment. Five-case report in teaching
      hospital Yalgado Ouedraogo of Ouagadougou].
AB  - The traditional products used to treat some pains can cause serious complications
      of which surgical abdomen. We listed in two years five cases of surgical abdomen
      complicating a traditional treatment in the service of digestive and general
      surgery of the hospital complex Yalgado Ouedraogo. There were two men and three
      women with an average age of 34,4 years. These traditional products were used to
      treat constipation, sexual impotence, sterility and to "posses" her husband. Oral
      and rectal routes were used by one and three patients respectively, another
      patient used triple routes (oral, rectal and vaginal). The digestive lesions were
      in the upper tract in one case (gastric phytobezoar), two patients presented
      acute intestinal occlusion and two others acute generalized peritonitis. All the
      five patients underwent laparotomy. Two patients died in immediately post
      operative course. The prevention of severe surgical complications of the
      digestive tract induced by traditional treatments has to be broadcasted through
      information, education and communication. 

PMID- 23857134
TI  - In vivo ultrasound molecular imaging of inflammatory thrombosis in arteries with
      cyclic Arg-Gly-Asp-modified microbubbles targeted to glycoprotein IIb/IIIa.
AB  - OBJECTIVE: Ultrasound molecular imaging has the potential to detect activated
      platelets, thus identifying atherosclerotic plaque instability before onset of
      serious clinical events. However, it has not been well defined in inflammatory
      arterial thrombosis. We hypothesized that microbubbles (MBs) target glycoprotein
      IIb/IIIa (GP IIb/IIIa) could achieve a noninvasive in vivo detection of
      inflammatory thrombosis in large arteries through contrast-enhanced ultrasound
      (CEU) imaging. MATERIALS AND METHODS: Lipid shell-based gas-filled MBs were
      modified covalently with a cyclic Arg-Gly-Asp (RGD) peptide (MB-cRGD) targeted to
      activated GP IIb/IIIa or a negative control peptide (MB-CON) via thiol-maleimide
      coupling. Adherence of MB-cRGD and MB-CON to GP IIb/IIIa was determined in vitro
      by using a parallel plate flow chamber at variable shear stress (0.5-8
      dynes/cm2). Inflammatory platelet thrombosis was induced by periadvential
      application of arachidonic acid (AA) to one of the bilateral carotids of C57BL/6
      mice (n = 20) and confirmed through intravital fluorescence microscopy.
      Attachment of MBs was determined in vivo with CEU imaging of bilateral carotids
      in the AA application mice with (n = 10) or without (n = 10) pretreatment of GP
      IIb/IIIa antagonist. The expression of integrin GP IIb/IIIa was assessed through
      immunohistochemistry. RESULTS: Microbubble-cRGD but not MB-CON had excellent
      affinity to GP IIb/IIIa under all shear stress conditions. Successful
      inflammatory platelet activation and thrombosis in AA application carotids were
      noted through intravital fluorescence microscopy. Contrast video intensity from
      adhered MB-cRGD in the thrombi was significantly higher than that from MB-CON (P
      < 0.05). Video intensity of MB-cRGD in the thrombi was suppressed significantly
      by preblocking with GP IIb/IIIa antagonist (P < 0.05) but not for MB-CON.
      Immunohistochemical finding demonstrates that expression of integrin GP IIb/IIIa
      in the thrombi was abundant; it was inhibited significantly through pretreatment
      with GP IIb/IIIa antagonist (P < 0.05). CONCLUSIONS: Cyclic RGD-modified MBs
      targeted to GP IIb/IIIa with CEU are capable of detecting inflammation-activated
      platelets and thrombosis in large arteries, thus providing a potential tool for
      identification of vulnerable atherosclerotic plaques.

PMID- 23857135
TI  - Intravascular enhancement with identical iodine delivery rate using different
      iodine contrast media in a circulation phantom.
AB  - PURPOSE: Both iodine delivery rate (IDR) and iodine concentration are decisive
      factors for vascular enhancement in computed tomographic angiography. It is
      unclear, however, whether the use of high-iodine concentration contrast media is
      beneficial to lower iodine concentrations when IDR is kept identical. This study
      evaluates the effect of using different iodine concentrations on intravascular
      attenuation in a circulation phantom while maintaining a constant IDR. MATERIALS
      AND METHODS: A circulation phantom with a low-pressure venous compartment and a
      high-pressure arterial compartment simulating physiological circulation
      parameters was used (heart rate, 60 beats per minute; stroke volume, 60 mL; blood
      pressure, 120/80 mm Hg). Maintaining a constant IDR (2.0 g/s) and a constant
      total iodine load (20 g), prewarmed (37 degrees C) contrast media with differing
      iodine concentrations (240-400 mg/mL) were injected into the phantom using a
      double-headed power injector. Serial computed tomographic scans at the level of
      the ascending aorta (AA), the descending aorta (DA), and the left main coronary
      artery (LM) were obtained. Total amount of contrast volume (milliliters), iodine
      delivery (grams of iodine), peak flow rate (milliliter per second), and
      intravascular pressure (pounds per square inch) were monitored using a dedicated
      data acquisition program. Attenuation values in the AA, the DA, and the LM were
      constantly measured (Hounsfield unit [HU]). In addition, time-enhancement curves,
      aortic peak enhancement, and time to peak were determined. RESULTS: All contrast
      injection protocols resulted in similar attenuation values: the AA (516 [11] to
      531 [37] HU), the DA (514 [17] to 531 [32] HU), and the LM (490 [10] to 507 [17]
      HU). No significant differences were found between the AA, the DA, and the LM for
      either peak enhancement (all P > 0.05) or mean time to peak (AA, 19.4 [0.58] to
      20.1 [1.05] seconds; DA, 21.1 [1.0] to 21.4 [1.15] seconds; LM, 19.8 [0.58] to
      20.1 [1.05] seconds). CONCLUSIONS: This phantom study demonstrates that constant
      injection parameters (IDR, overall iodine load) lead to robust enhancement
      patterns, regardless of the contrast material used. Higher iodine concentration
      itself does not lead to higher attenuation levels. These results may stimulate a
      shift in paradigm toward clinical usage of contrast media with lower iodine
      concentrations (eg, 240 mg iodine/mL) in individual tailored contrast protocols.
      The use of low-iodine concentration contrast media is desirable because of the
      lower viscosity and the resulting lower injection pressure.

PMID- 23857137
TI  - Ultrasound molecular imaging of E-selectin in tumor vessels using poly n-butyl
      cyanoacrylate microbubbles covalently coupled to a short targeting peptide.
AB  - OBJECTIVES: The purposes of this study were the development and preclinical
      evaluation of clinically translatable E-selectin-specific ultrasound contrast
      agents based on a peptide ligand with the recognition sequence IELLQAR. MATERIALS
      AND METHODS: The E-selectin-specific peptide was synthesized through solid phase
      peptide synthesis and covalently attached to poly n-butylcyanoacrylate-stabilized
      microbubbles with an air core. Quantification of the microbubble surface coverage
      with peptides was performed through flow cytometry. Targeted adhesion of peptide
      coated microbubbles was investigated in vitro using parallel plate flow chamber
      assays on tumor necrosis factor-alpha-stimulated human umbilical vein endothelial
      cells. In vivo imaging was performed in nude mice bearing human ovarian carcinoma
      xenografts (MLS), followed by ex vivo immunohistochemistry validation of E
      selectin expression. RESULTS: Success of peptide synthesis was validated through
      preparative reverse phase high-pressure liquid chromatography and electronspray
      ionization-mass spectrometry. Results of the flow cytometry revealed
      approximately 4000 E-selectin-specific peptides/microbubble surface. Results of
      the in vitro experiments demonstrated the specificity of peptide-coated
      microbubbles to E-selectin (1.10 +/- 0.48 vs 0.19 +/- 0.09 bound microbubbles per
      cell, before and after competition respectively; P < 0.01). The in vivo imaging
      enabled specific assessment of E-selectin expression in MLS carcinoma xenografts
      (5.21 +/- 3.41 vs 1.37 +/- 0.67 contrast intensity before and after competition,
      respectively; P < 0.05). CONCLUSIONS: Clinically translatable microbubbles that
      were covalently coupled to the short E-selectin-specific peptide (IELLQAR)
      enabled specific imaging of the E-selectin expression in tumor vessels in vivo.

PMID- 23857136
TI  - Quantification of thoracic blood flow using volumetric magnetic resonance imaging
      with radial velocity encoding: in vivo validation.
AB  - OBJECTIVES: The objective of this study was to validate radially undersampled 5
      point velocity-encoded time-resolved flow-sensitive magnetic resonance imaging
      (MRI) ("PC-VIPR", phase contrast vastly undersampled imaging with isotropic
      resolution projection reconstruction magnetic resonance) for the quantification
      of ascending aortic (AAO) and main pulmonary artery (MPA) flow in vivo. MATERIALS
      AND METHODS: Data from 18 healthy volunteers (41.6 +/- 16.2 years [range, 22-73
      years]; body mass index, 26.0 +/- 3.5 [19.1-31.4]) scanned at 3 T with a 32
      channel coil were included. The left and right ventricular stroke volumes
      calculated from contiguous short-axis CINE-balanced steady state free precession
      (CINE-bSSFP) slices were used as the primary reference for cardiac output. Flow
      measured from 2-dimensional phase contrast MRI (2D-PC-MRI) in the AAO and the MPA
      served as the secondary reference. Time-resolved 4-dimensional flow-sensitive MRI
      (4D flow MRI) using PC-VIPR was performed with a velocity sensitivity of Venc =
      150 cm/s reconstructed to 20 time frames at 1.4-mm isotropic spatial resolution.
      In 11 of 20 volunteers, phantom-corrected 4D flow MRI data were also assessed.
      Differences between methods of calculating the left ventricular and right
      ventricular cardiac output were assessed with the Bland-Altman analysis (BA, mean
      difference +/-2SD). The QP/QS-ratio was calculated for each method. RESULTS:
      Initially, PC-VIPR compared unfavorably with CINE-bSSFP (left ventricular stroke
      volume: 96.5 +/- 14.4 mL; right ventricular stroke volume: 93.6 +/- 14.0 mL vs
      81.2 +/- 24.3 mL [AAO] and 85.6 +/- 25.4 mL [MPA]; P = 0.027 and 0.25) with BA
      differences of -14.6 +/- 44.0 mL (AAO) and -9.0 +/- 45.9 mL (MPA). Whereas
      phantom correction had minor effects on 2D-PC-MRI results and comparison with
      CINE-bSSFP, it improved PC-VIPR results: BA differences between CINE-bSSFP and PC
      VIPR after correction were -1.4 +/- 15.3 mL (AAO) and -4.1 +/- 16.1 mL (MPA); BA
      comparison with 2D-PC-MRI improved to -12.0 +/- 48.1 mL (AAO) and -2.2 +/- 19.5
      mL (MPA). QP/QS-ratio results for all techniques were within physiologic limits.
      CONCLUSIONS: Accurate quantification of AAO and MPA flows with radially
      undersampled 4D flow MRI applying 5-point velocity encoding is achievable when
      phantom correction is used.

PMID- 23857138
TI  - Letter to the editor regarding "A quantitative and comprehensive method to
      analyze human milk oligosaccharide structures in the urine and feces of infants".

PMID- 23857139
TI  - Response to letter to the editor regarding "A quantitative and comprehensive
      method to analyze human milk oligosaccharide structures in the urine and feces of
      infants".

PMID- 23857140
TI  - Development and validation of LC-MS/MS method for determination of very long acyl
      chain (C22:0 and C24:0) ceramides in human plasma.
AB  - Ceramide is a key metabolite in both anabolic and catabolic pathways of
      sphingolipids. The very long fatty acyl chain ceramides N-(docosanoyl)-sphing-4
      enine (Cer(22:0)) and N-(tetracosanoyl)-sphing-4-enine (Cer(24:0)) are associated
      with multiple biological functions. Elevated levels of these sphingolipids in
      tissues and in the circulation have been associated with insulin resistance and
      diabetes. To facilitate quantification of these very long chain ceramides in
      clinical samples from human subjects, we have developed a sensitive, accurate,
      and high-throughput assay for determination of Cer(22:0) and Cer(24:0) in human
      plasma. Cer(22:0) and Cer(24:0) and their deuterated internal standards were
      extracted by protein precipitation and chromatographically separated by HPLC. The
      analytes and their internal standards were ionized using positive-ion
      electrospray mass spectrometry, then detected by multiple-reaction monitoring
      with a tandem mass spectrometer. Total liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) runtime was 5 min. The assay exhibited a linear dynamic
      range of 0.02-4 and 0.08-16 MUg/ml for Cer(22:0) and Cer(24:0), respectively, in
      human plasma with corresponding absolute recoveries from plasma at 109 and 114 %,
      respectively. The lower limit of quantifications were 0.02 and 0.08 MUg/ml for
      Cer(22:0) and Cer(24:0), respectively. Acceptable precision and accuracy were
      obtained for concentrations over the calibration curve ranges. With the semi
      automated format and short LC runtime for the assay, a throughput of ~200
      samples/day can easily be achieved. 

PMID- 23857141
TI  - A new treatment by dispersive liquid-liquid microextraction for the determination
      of parabens in human serum samples.
AB  - Alkyl esters of p-hydroxybenzoic acid (parabens) are a family of compounds that
      have been in use since the 1920s as preservatives in cosmetic formulations, with
      one of the lowest rates of skin problems reported in dermatological patients.
      However, in the last few years, many scientific publications have demonstrated
      that parabens are weak endocrine disruptors, meaning that they can interfere with
      the function of endogenous hormones, increasing the risk of breast cancer. In the
      present work, a new sample treatment method is introduced based on dispersive
      liquid-liquid microextraction for the extraction of the most commonly used
      parabens (methyl-, ethyl-, propyl-, and butylparaben) from human serum samples
      followed by separation and quantification using ultrahigh performance liquid
      chromatography-tandem mass spectrometry. The method involves an enzymatic
      treatment to quantify the total content of parabens. The extraction parameters
      (solvent and disperser solvent, extractant and dispersant volume, pH of the
      sample, salt addition, and extraction time) were accurately optimized using
      multivariate optimization strategies. Ethylparaben ring (13)C6-labeled was used
      as surrogate. Limits of quantification ranging from 0.2 to 0.7 ng mL(-1) and an
      interday variability (evaluated as relative standard deviations) from 3.8 to 11.9
      % were obtained. The method was validated using matrix-matched calibration
      standard and a spike recovery assay. Recovery rates for spiked samples ranged
      from 96 to 106 %, and a good linearity up to concentrations of 100 ng mL(-1) was
      obtained. The method was satisfactorily applied for the determination of target
      compounds in human serum samples. 

PMID- 23857143
TI  - Long-term follow-up analysis of zolpidem in fingernails after a single oral dose.
AB  - The determination of xenobiotics in keratinized matrices, such as nails and hair,
      has received considerable attention because of the relatively long detection
      window for compounds. The distribution of xenobiotics in fingernails, unlike
      hair, was equivocal. The main aim of this study was to use follow-up surveys to
      measure zolpidem profiles in nails after subjects consumed a single dose of the
      drug. In addition, the zolpidem concentrations in nails were compared with data
      for different biosamples, such as hair and blood from previous work. With these
      preconditions, a high-performance liquid chromatography-tandem mass spectrometry
      method was developed and validated for the determination of zolpidem in nails.
      Nails underwent alkaline hydrolysis and were extracted with diethyl ether. A
      Capcell Pak C18 MGII column was used to separate the target compound, and an API
      4000 Qtrap mass spectrometer was used as a detector. The results for nail samples
      from seven subjects who had taken a single 10 mg zolpidem dose were significant:
      two relatively high zolpidem concentrations were observed in the long-term follow
      up analysis of nails. The zolpidem concentration was less than 1.74 pg/mg and
      less than 3.29 pg/mg in fingernails and toenails, respectively. The subsequent
      peak concentration of zolpidem was observed between 10 and 15 weeks after each
      subject took a single dose of the drug. This result suggested that the germinal
      matrix area was a primary in vivo pathway for zolpidem secretion into the nail.
      The analysis of biosamples, such as nails, may be a useful adjunct to
      conventional methods of drug testing and hair analysis. Further research is
      needed concerning the contamination risk in analysis of nail biosamples. 

PMID- 23857142
TI  - Discrimination between genetically identical peony roots from different regions
      of origin based on 1H-nuclear magnetic resonance spectroscopy-based metabolomics:
      determination of the geographical origins and estimation of the mixing
      proportions of blended samples.
AB  - Sixty peony root training samples of the same age were collected from various
      regions in Korea and China, and their genetic diversity was investigated for 23
      chloroplast intergenic space regions. All samples were genetically
      indistinguishable, indicating that the DNA-based techniques employed were not
      appropriate for determining the samples' regions of origin. In contrast, (1)H
      nuclear magnetic resonance ((1)H-NMR) spectroscopy-based metabolomics coupled
      with multivariate statistical analysis revealed a clear difference between the
      metabolic profiles of the Korean and Chinese samples. Orthogonal projections on
      the latent structure-discrimination analysis allowed the identification of
      potential metabolite markers, including gamma-aminobutyric acid, arginine,
      alanine, paeoniflorin, and albiflorin, that could be useful for classifying the
      samples' regions of origin. The validity of the discrimination model was tested
      using the response permutation test and blind prediction test for internal and
      external validations, respectively. Metabolomic data of 21 blended samples
      consisting of Korean and Chinese samples mixed at various proportions were also
      acquired by (1)H-NMR analysis. After data preprocessing which was designed to
      eliminate uncontrolled deviations in the spectral data between the testing and
      training sets, a new statistical procedure for estimating the mixing proportions
      of blended samples was established using the constrained least squares method for
      the first time. The predictive procedure exhibited relatively good predictability
      (adjusted R (2) = 0.7669), and thus has the potential to be used in the quality
      control of peony root by providing correct indications for a sample's
      geographical origins. 

PMID- 23857144
TI  - Tendinopathy and its treatment with platelet-rich plasma (PRP).
AB  - This article has two goals. First, it reviews studies on tendinopathy in the
      literature while highlighting the following points: a) tendinopathy refers to a
      spectrum of tendon disorders with multiple facets of "tissue phenotypes," and b)
      mechanical loading is a major factor that contributes to the development of
      tendinopathy by inducing the aberrant differentiation of tendon stem/progenitor
      cells into non-tenocyte cell lineages. Second, the current treatments of
      tendinopathy with platelet-rich plasma (PRP) are briefly described, issues
      related to PRP treatment in clinics are highlighted, and the needs for basic
      science research on clinical usage of PRP for tendinopathy treatment are
      discussed.

PMID- 23857145
TI  - The effect of solicitations on grooming exchanges among female Japanese macaques
      at Katsuyama.
AB  - In group-living primates, individuals often exchange grooming with not only kin
      but also non-kin. We investigated the effect of soliciting behaviors on grooming
      exchanges in a free-ranging Japanese macaque (Macaca fuscata) group at Katsuyama.
      In this study, we used a focal animal sampling method, targeting 14 females. Data
      were collected for 15.75 +/- 2.67 (mean +/- SD) hours per focal female. We
      classified female-female pairs into three pair types: kin pairs, affiliated non
      kin pairs, and unaffiliated non-kin pairs. Females received grooming more
      frequently when they solicited after grooming their partners than when they did
      not solicit in all pair types. In addition, females received grooming less
      frequently when they did not groom their unaffiliated non-kin partners before
      soliciting; prior grooming was not needed to receive grooming from kin or
      affiliated non-kin partners. The degree of grooming reciprocity did not differ
      according to the frequency with which females in kin or affiliated non-kin pairs
      solicited after grooming. On the other hand, grooming reciprocity between
      unaffiliated non-kin females was more balanced when they solicited frequently
      after grooming, as compared with when they did not. In conclusion, our study
      suggests that soliciting behaviors promote grooming exchanges in female Japanese
      macaques.

PMID- 23857146
TI  - Preliminary observation of dynamic changes in alcohol concentration in the human
      brain with proton magnetic resonance spectroscopy on a 3T MR instrument.
AB  - PURPOSE: Our purposes were to establish suitable conditions for proton magnetic
      resonance spectroscopy (MRS) to measure dynamic changes in alcohol concentration
      in the human brain, to evaluate these changes, and to compare the findings with
      data from analysis of breath vapor and blood samples. MATERIALS AND METHODS: We
      evaluated 4 healthy volunteers (mean age 26.5 years; 3 males, one female) with no
      neurological findings. All studies were performed with 3-tesla clinical equipment
      using an 8-channel head coil. We applied our modified single-voxel point-resolved
      spectroscopy (PRESS) sequence. Continuous measurements of MRS, breath vapor, and
      blood samples were conducted before and after the subjects drank alcohol with a
      light meal. The obtained spectra were quantified by LCModel Ver. 6.1, and the
      accuracy of the MRS measurements was estimated using the estimated standard
      deviation expressed in percentage (%SD) as a criterion. RESULTS: Alcohol peaks
      after drinking were clearly detected at 1.2 ppm for all durations of measurement.
      Good correlations between breath vapor or blood sample and MRS were found by sub
      minute MRS measurement. The continuous measurement showed time-dependent changes
      in alcohol in the brain and various patterns that differed among subjects.
      CONCLUSIONS: The clinical 3T equipment enables direct evaluation of sub-minute
      changes in alcohol metabolism in the human brain.

PMID- 23857147
TI  - Automatic extraction of the cingulum bundle in diffusion tensor tract-specific
      analysis: feasibility study in Parkinson's disease with and without dementia.
AB  - PURPOSE: Tract-specific analysis (TSA) measures diffusion parameters along a
      specific fiber that has been extracted by fiber tracking using manual regions of
      interest (ROIs), but TSA is limited by its requirement for manual operation, poor
      reproducibility, and high time consumption. We aimed to develop a fully automated
      extraction method for the cingulum bundle (CB) and to apply the method to TSA in
      neurobehavioral disorders such as Parkinson's disease (PD). MATERIALS AND
      METHODS: We introduce the voxel classification (VC) and auto diffusion tensor
      fiber-tracking (AFT) methods of extraction. The VC method directly extracts the
      CB, skipping the fiber-tracking step, whereas the AFT method uses fiber tracking
      from automatically selected ROIs. We compared the results of VC and AFT to those
      obtained by manual diffusion tensor fiber tracking (MFT) performed by 3
      operators. We quantified the Jaccard similarity index among the 3 methods in data
      from 20 subjects (10 normal controls [NC] and 10 patients with Parkinson's
      disease dementia [PDD]). We used all 3 extraction methods (VC, AFT, and MFT) to
      calculate the fractional anisotropy (FA) values of the anterior and posterior CB
      for 15 NC subjects, 15 with PD, and 15 with PDD. RESULTS: The Jaccard index
      between results of AFT and MFT, 0.72, was similar to the inter-operator Jaccard
      index of MFT. However, the Jaccard indices between VC and MFT and between VC and
      AFT were lower. Consequently, the VC method classified among 3 different groups
      (NC, PD, and PDD), whereas the others classified only 2 different groups (NC, PD
      or PDD). CONCLUSION: For TSA in Parkinson's disease, the VC method can be more
      useful than the AFT and MFT methods for extracting the CB. In addition, the
      results of patient data analysis suggest that a reduction of FA in the posterior
      CB may represent a useful biological index for monitoring PD and PDD.

PMID- 23857148
TI  - Estimation of perilymph enhancement after intratympanic administration of Gd-DTPA
      by fast T1-mapping with a dual flip angle 3D spoiled gradient echo sequence.
AB  - Eleven patients with suspected Meniere's disease received intratympanic (IT)
      administration of gadolinium (gadopentetate dimeglumine; Gd) prior to acquisition
      of 3-dimensional (3D) fluid-attenuated inversion recovery (FLAIR), 3D real
      inversion recovery (IR), and fast T1 mapping by dual flip angle 3D gradient echo
      (FT1-map) imaging sequences to evaluate the degree of perilymph enhancement.
      Though 3-dimensional FLAIR could detect lower concentrations of gadolinium than
      3D real IR, in 2 patients, poor enhancement still prevented visualization of the
      endolymphatic space using 3D FLAIR. We could predict poor contrast enhancement in
      these 2 patients using the FT1-map technique.

PMID- 23857149
TI  - Diffusion tensor imaging analysis for psychiatric disorders.
AB  - The pathophysiology of psychiatric disorders is complex and cannot be easily
      assessed by laboratory studies. Diffusion tensor imaging (DTI) is a magnetic
      resonance imaging technique increasingly used for noninvasive and quantitative
      evaluation of abnormalities of the cerebral white matter because it provides
      exquisite details on tissue microstructures and also can perform sophisticated
      computer-based analyses. We review basic principles of DTI; methods of diffusion
      tensor analysis; recent DTI findings in major psychiatric diseases, such as
      schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorder;
      and factors to keep in mind when interpreting the results of DTI analysis. We
      recommend the frequent use of DTI as a routine clinical protocol to assess white
      matter abnormalities in patients with psychiatric disorders. 

PMID- 23857150
TI  - Rules, roles, and room for discussion in gadoxetic acid-enhanced magnetic
      resonance liver imaging: current knowledge and future challenges.
AB  - Since its launch onto the world medical market, gadoxetic acid has received a
      great deal of attention from a diverse group of researchers, including
      gastroenterologists, hepatologists, and abdominal radiologists. Gadoxetic acid in
      liver magnetic resonance (MR) imaging might be considered to have excellent
      utility. However, several issues remain that radiologists should keep in mind
      when utilizing this product. We compiled this review to introduce gadoxetic acid,
      describe how it should be used, highlight the situations in which it is most and
      least reliable, and suggest potential avenues for future research. 

PMID- 23857151
TI  - Correlations between apparent diffusion coefficient values and prognostic factors
      of breast cancer.
AB  - PURPOSE: We investigated possible correlations between apparent diffusion
      coefficient (ADC) values and prognostic factors of breast cancer. METHODS: We
      retrospectively evaluated 81 patients who underwent magnetic resonance (MR)
      imaging of the breast and were diagnosed pathologically with invasive ductal
      carcinoma (IDC) not otherwise specified with invasive foci one cm or larger. We
      excluded ductal carcinoma in situ and IDC with invasive foci smaller than one cm
      because small lesions decrease the reliability of signal intensity of diffusion
      weighted imaging (DWI). We also excluded special type cancers. We used t-test to
      compare the mean ADC values of cancers of Stage pT1 (<=2 cm) versus pT2 or 3 (>2
      cm), cancers with versus without vascular invasion, axillary lymph node (N)
      positive versus N-negative cancers, estrogen receptor (ER)-positive versus ER
      negative cancers, and progesterone receptor (PgR)-positive versus PgR-negative
      cancers. We analyzed correlations between the ADC value with nuclear grade (NG)
      and human epidermal growth factor receptor 2 (HER2) score by rank test using
      Spearman's correlation coefficient. RESULTS: The mean ADC value was significantly
      higher for N-positive (n=28; 0.97 +/- 0.20 * 10(-3) mm(2)/s) than N-negative
      cancers (n=53; 0.87 +/- 0.17 * 10(-3) mm(2)/s) (P=0.017); significantly lower for
      ER-positive (n=63; 0.88 +/- 0.15 * 10(-3) mm(2)/s) than ER-negative cancers
      (n=18; 1.01 +/- 0.21 * 10(-3) mm(2)/s) (P=0.005); and significantly lower for PgR
      positive (n=47; 0.88 +/- 0.16 * 10(-3) mm(2)/s) than PgR-negative cancers (n=34;
      0.95 +/- 0.18 * 10(-3) mm(2)/s) (P=0.048). Tumor size, vascular invasion, NG, and
      HER2 status showed no significant correlation with ADC values. CONCLUSION: ADC
      values were higher for N-positive and ER-negative breast cancers than N-negative
      and ER-positive cancers.

PMID- 23857152
TI  - Diffusion-weighted imaging of the breast: comparison of b-values 1000 s/mm2 and
      1500 s/mm2.
AB  - PURPOSE: We compared diffusion-weighted imaging (DWI) of the breast using 2
      different b-values to determine the optimal b-value for greatest signal contrast
      between tumors and normal tissue of the breast. MATERIALS AND METHODS: We
      performed DWI of the breast at b-values of 1000 s/mm(2) and 1500 s/mm(2) in 120
      patients (121 lesions, 19 benign, 102 malignant) and visually scored image
      quality with regard to artifact and visibility of tumors. We quantitatively
      evaluated the signal-to-noise ratio (SNR) of the tumor and contrast-to-noise
      ratio (CNR) and contrast ratio (CR) between the tumor and normal breast
      parenchyma. RESULTS: The CR of invasive carcinoma (IC), ductal carcinoma in situ
      (DCIS), and benign tumors significantly improved with b=1500 s/mm(2) compared
      with b=1000 s/mm(2). The SNR and CNR were significantly lower with b=1500 s/mm(2)
      than b=1000 s/mm(2) despite the increasing number of excitations at b=1500
      s/mm(2). At b=1500 s/mm(2), the difference in SNR, CNR, and CR between IC and
      DCIS and benign tumors was statistically significant. CONCLUSION: DWI may depict
      breast tumors more clearly with b=1500 s/mm(2) than b=1000 s/mm(2).

PMID- 23857153
TI  - Ocular MR imaging: evaluation of different coil setups in a phantom study.
AB  - PURPOSE: Small loop surface coils are generally recommended for ocular magnetic
      resonance (MR) imaging, but the optimal coil setup has not been systematically
      investigated. In this phantom study, we investigated which coil setup of those
      coils available for our MR imaging system provides the highest signal-to-noise
      ratio (SNR) in ocular MR imaging at 1.5 tesla. MATERIALS AND METHODS: Using a
      phantom to simulate the eyeball and the orbital fat, we employed loop surface
      coils of 4- and 6-cm diameter and a multi-channel head coil to obtain images
      using a T1-weighted spin-echo sequence and then measured the SNR for each coil
      and coil combination. RESULTS: Use of the 6-cm loop coil alone yielded the
      highest mean SNR (27.5). Even in superficial regions (mesial and temporal), the
      SNR was higher using the 6-cm loop coil (33.6 and 45.5) than the 4-cm loop coil
      (28.0 and 33.8). Additional use of the head coil reduced the mean SNR to 10.4.
      CONCLUSION: This quantitative analysis suggests that use of a 6-cm loop surface
      coil offers the best results in ocular MR imaging. Combinations of loop coils or
      additional use of a head coil cannot be recommended because higher noise degrades
      image quality.

PMID- 23857154
TI  - A Post-processing framework for localized 2D MR spectroscopy in vivo.
AB  - PURPOSE: We propose a post-processing framework for localized two-dimensional
      (2D) magnetic resonance spectroscopy (MRS) in vivo. METHODS: Our framework
      consists of corrections on eddy current and subject motion along with the
      framework used in conventional analytical 2D nuclear magnetic resonance (NMR)
      spectroscopy. In the eddy current correction, the phases of the free induction
      decays (FIDs) of the metabolite (1)H are corrected along the t2 direction by the
      phase of the FID of water (1)H. The corrected FIDs are Fourier transformed along
      the t2 direction, and interferograms of F(t1, omega2) are calculated. In the
      motion correction, the zero-order phase of the N-acetyl aspartate (NAA) singlet
      peak for each t1 axis is corrected after correction of frequency drift. We
      applied this framework in phantom and human brain measurements in a 4.7T whole
      body MR system. Two-dimensional data were collected by the localized 2D constant
      time correlation spectroscopy (CT-COSY) sequence. We used a phantom containing a
      brain metabolite mixture of NAA, creatine (Cr), glutamate (Glu), glutamine (Gln)
      and gamma-amino butyric acid (GABA). We demonstrated the eddy current correction
      procedure in the phantom experiments and the subject motion correction in human
      measurements. RESULTS: Though asymmetric patterns of the singlets of NAA and Cr
      were shown around the peak along the F2 direction in the reconstructed phantom
      spectra without eddy current correction, symmetric patterns arose after the
      correction. The t1 noise caused by those singlets was found in the human brain
      spectra without motion correction. The t1 noise was sufficiently suppressed by
      the motion correction. CONCLUSION: Our proposed post-processing framework for
      localized 2D MRS can improve the quality of in vivo 2D spectra and may allow
      improved quantitation and robustness of in vivo 2D spectroscopy.

PMID- 23857155
TI  - Optimization of scan parameters for T1-FLAIR imaging at 1.5 and 3T using computer
      simulation.
AB  - PURPOSE: We attempted to optimize scan parameters for T1-weighted fluid
      attenuated inversion recovery (T1-FLAIR) sequence at 3 and 1.5 tesla (T) using
      computer simulation. METHODS: We measured the T1 and T2 relaxation time values
      (T1v and T2v) of gray (GM) and white matter (WM) at 3 and 1.5T, generated
      computer-simulated T1-FLAIR (CS-T1-FLAIR) images using those values, and compared
      the simulated and actual T1-FLAIR images to verify the contrast reliability of
      our computer simulation. We mathematically and visually evaluated CS-T1-FLAIR
      images at various repetition times (TR) and echo times (TE). RESULTS: At 3T, the
      measured relaxation values for GM were T1v, 1524 ms, and T2v, 85 ms, and for WM,
      T1v, 750 ms, and T2v, 65 ms. At 1.5T, the measured relaxation values for GM were
      T1v, 1251 ms, and T2v, 99 ms, and for WM, T1v, 623 ms, and T2v, 75 ms. Contrast
      of CS-T1-FLAIR and actual T1-FLAIR images was identical. An optimal TR of 3140 ms
      was determined for T1-FLAIR at 3T and 2440 ms at 1.5T based on mathematical
      evaluation. The optimal TR ranges were 2400 to 3900 ms at 3T and 1800 to 3200 ms
      at 1.5T based on visual assessment of CS-T1-FLAIR. A shorter TE provided better
      T1 contrast. CONCLUSION: We optimized T1-FLAIR by focusing on its most important
      scan parameters using computer simulations and determined that a longer TR was
      suitable at 3T than at 1.5T. Our computer simulation was useful for determining
      the optimal scan parameters.

PMID- 23857156
TI  - Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts.
AB  - In abnormal skin wound healing, hypertrophic scars (HS) are characterized by
      excessive fibroblast hypercellularity and an overproduction of collagen, leading
      to atypical extracellular matrix (ECM) remodeling. Although the exact mechanisms
      of HS remain unclear, decreased HS fibroblast (HSFB) apoptosis and increased
      proliferation are evident in the development of HS. In this study, the
      contribution of the second mitochondria-derived activator of caspases/direct
      inhibitor of apoptosis protein (IAP)-binding protein with a low isoelectric point
      (pI) (Smac/DIABLO), an apoptosis-promoting protein released from the
      mitochondria, was investigated in human normal skin and HSFB cultures. The
      expression of Smac/DIABLO is usually decreased in many malignant tumors compared
      with normal tissues. Immunohistochemical analysis of skin tissues and the western
      blot analyses of fibroblasts revealed that the expression of Smac/DIABLO was
      lower in HS tissues compared with normal skin tissues. Of note, adenovirus
      mediated Smac/DIABLO overexpression in the cultured HSFBs significantly reduced
      cell proliferation, as detected by the cell counting kit-8, and increased caspase
      3 and -9 activity, as detected by spectrofluorimetry. In addition, it increased
      apoptosis, as detected by fluorescence-activated cell sorting (FACS).
      Furthermore, we found that the silencing of Smac with siRNA in the HSFBs induced
      a noticeable decrease in caspase-3 and -9 activity, leading to a significant
      reduction in apoptosis. In addition, the mRNA expression of type I and III pro
      collagen detected in the HSFBs was significantly increased following the
      silencing of Smac with siRNA and was inhibited following Smac/DIABLO
      overexpression, as shown by real-time RT-PCR. In conclusion, Smac/DIABLO
      decreases the proliferation and increases the apoptosis of HSFBs. To our
      knowledge, the data from our study suggest for the first time that Smac/DIABLO is
      a novel therapeutic target for HS.

PMID- 23857157
TI  - Combined staining for immunohistochemical markers in the diagnosis of papillary
      thyroid carcinoma: improvement in the sensitivity or specificity?
AB  - OBJECTIVES: To investigate the ability of cytokeratin (CK)-19, galectin-3, human
      bone marrow endothelial cell (HBME)-1 and tyrosine kinase-type cell surface
      receptor HER2 (HER-2/neu) to differentiate papillary thyroid carcinoma (PTC) from
      benign thyroid nodules. METHODS: Archival specimens of PTC and benign thyroid
      nodules were included in this retrospective immunohistochemical study. CK-19,
      galectin-3, HBME-1, and HER-2/neu protein levels were analysed
      immunohistochemically using routinely prepared tissue sections. RESULTS:
      Specimens from 331 patients with PTC and 664 patients with benign thyroid nodules
      were reviewed. For all four protein markers, the percentage of samples with cells
      that demonstrated positive immunostaining was significantly higher in PTC
      specimens than in benign thyroid nodules. As a single protein marker, CK-19 was
      the most sensitive (92.7%) and HBME-1 was the most specific (97.9%). The
      combination of CK-19 and galectin-3 was the most sensitive (82.8%), and the
      combinations of HBME-1 with CK-19 or galectin-3 or HER-2/neu were the most
      specific (98.3%). CONCLUSIONS: The combination of HBME-1 and either CK19 or
      galectin-3 or HER-2/neu can improve the specificity of the diagnosis of PTC.

PMID- 23857158
TI  - Serum concentrations of A disintegrin and metalloproteinase 9 (ADAM9) mRNA as a
      promising novel marker for the detection of pulmonary sarcoidosis.
AB  - AIMS: This prospective study investigated the potential role of serum A
      disintegrin and metalloproteinase 9 (ADAM9) mRNA in the differential diagnosis of
      pulmonary sarcoidosis from other diseases with similar clinical presentations,
      such as tuberculosis (TB). METHODS: Serum samples were collected from patients
      with sarcoidosis, and compared with those from patients with TB and healthy
      control subjects. Real-time quantitative reverse transcription-polymerase chain
      reaction was performed to measure the concentration of ADAM9 mRNA relative to the
      internal control, glyceraldehyde-3-phosphate dehydrogenase. RESULTS: A total of
      100 patients with sarcoidosis were compared with 50 patients with TB and 50
      healthy control subjects. The serum concentration of ADAM9 mRNA in patients with
      sarcoidosis was significantly lower than that in healthy control subjects and
      patients with TB. The serum concentration of ADAM9 mRNA in patients with TB was
      significantly higher than that in healthy control subjects. CONCLUSION: These
      data suggest that serum ADAM9 mRNA might be a potential biomarker for the
      differential diagnosis of pulmonary sarcoidosis.

PMID- 23857159
TI  - Factors associated with intensive care unit admission in patients with traumatic
      thoracic injury.
AB  - OBJECTIVE: To identify factors associated with intensive care unit (ICU)
      admission in patients with traumatic thoracic injury. METHODS: Data for
      consecutive patients with thoracic trauma were collected prospectively. Outcomes
      were requirement for ICU care and prolonged (>7 days) ICU care. RESULTS: The
      study included 1333 patients, 484 (36.3%) of whom received ICU care: 125 of these
      (25.8%) received prolonged ICU care. Head injury, abdominal injury, injury
      severity score >= 16, haemothorax, chest tube placement and spinal surgery were
      significantly associated with ICU care. Head injury, number of rib fractures,
      chest drain placement, spinal surgery and extremity surgery were independent risk
      factors for prolonged ICU care. CONCLUSIONS: Associated injury factors played a
      more prominent role than thoracic factors in the need for ICU and prolonged ICU
      care. A multidisciplinary trauma team (involving neurosurgeons, abdominal
      surgeons, orthopaedic surgeons and thoracic surgeons) is essential for the care
      of patients with traumatic thoracic injury.

PMID- 23857160
TI  - The effect of anaesthesia technique on maternal and cord blood ischaemia-modified
      albumin levels during caesarean section: a randomized controlled study.
AB  - OBJECTIVE: Ischaemia-modified albumin (IMA) is an early marker for various
      ischaemic events, including cardiac ischaemia. This study determined variations
      in IMA levels during caesarean section, performed under general anaesthesia or
      with combined spinal epidural anaesthesia. METHODS: Full-term, healthy pregnant
      women were allocated to undergo caesarean section, using either general
      anaesthesia or combined spinal epidural anaesthesia. IMA and albumin levels were
      measured in maternal serum samples taken immediately prior to caesarean section
      and 30 min into the procedure, as well as from serum taken from cord blood after
      double clamping. RESULTS: At total of 51 healthy pregnant women underwent either
      general anaesthesia (n = 28) or combined spinal epidural anaesthesia (n = 23).
      Within-group analysis of the general anaesthesia group showed that both IMA
      levels and IMA/albumin ratios were significantly higher at 30 min of surgery
      compared with the immediate preoperative period. CONCLUSIONS: Lower IMA levels in
      the combined spinal epidural anaesthesia group may have been due to improved
      balancing of oxidative stress during caesarean section. Further research on IMA
      levels during caesarean section should take into account the method of
      anaesthesia used.

PMID- 23857161
TI  - The human impact of earthquakes: a historical review of events 1980-2009 and
      systematic literature review.
AB  - Introduction. Population growth and increasing urbanization in earthquake-prone
      areas suggest that earthquake impacts on human populations will increase in the
      coming decades. Recent large earthquakes affecting large populations in Japan,
      Haiti, Chile and New Zealand are evidence of this trend and also illustrate
      significant variations in outcomes such damage and mortality levels. The
      objectives of this review were to describe the impact of earthquakes on human
      populations in terms of mortality, injury and displacement and, to the extent
      possible, identify risk factors associated with these outcomes. This is one of
      five reviews on the human impact of natural disasters. Methods. Data on the
      impact of earthquakes were compiled using two methods, a historical review from
      1980 to mid 2009 of earthquake events from multiple databases and a systematic
      literature review of publications, ending in October 2012. Analysis included
      descriptive statistics and bivariate tests for associations between earthquake
      mortality and characteristics using STATA 11. Findings. From 1980 through 2009,
      there were a total of 372,634 deaths (range 314,634-412,599), 995,219 injuries
      (range: 845,345-1,145,093), and more than 61 million people affected by
      earthquakes, and mortality was greatest in Asia. Inconsistent reporting across
      data sources suggests that the numbers injured and affected are likely
      underestimates. Findings from a systematic review of the literature indicate that
      the primary cause of earthquake-related death was trauma due to building collapse
      and, the very young and the elderly were at increased mortality risk, while
      gender was not consistently associated with mortality risk. Conclusions.
      Strategies to mitigate the impact of future earthquakes should include
      improvements to the built environment and a focus on populations most vulnerable
      to mortality and injury. 

PMID- 23857162
TI  - What should we tell patients with heart failure about sodium restriction and how
      should we counsel them?
AB  - This article is a review of current evidence regarding the recommended level of
      dietary sodium, involvement of family members in adoption of a low sodium diet,
      and evidence-based strategies to increase patient and family member willingness
      and ability to a follow a low sodium diet. The available evidence suggests that
      recommending a 2.5 to 3 g sodium diet will meet nutritional needs and decrease
      risk of hospitalizations. The best strategy identified for patient success is to
      fully involve both patients and family members in jointly reducing sodium intake.
      Motivational interviewing techniques should be used before counseling begins to
      guide patients and family members toward realization of the need to follow a low
      sodium diet. Successful counseling starts with determining perceptions, barriers,
      and individual characteristics that impede adherence. This information is
      incorporated into theory-based teaching strategies to promote behavior change and
      successful adoption of a low sodium diet.

PMID- 23857163
TI  - The situation of caregivers in heart failure and their role in improving patient
      outcomes.
AB  - This paper describes experiences of caregivers to patients with heart failure and
      their role in improving patient outcomes. Being related to and caring for someone
      with heart failure involves several prominent changes in daily life that may
      sometimes be experienced as stressful and burdensome. Since heart failure is a
      chronic condition, the burden will be permanent and sometimes increases during
      the illness trajectory. Caregiver burden increases if the caregiver experiences
      poor mental and/or physical health, limitations in daily life, isolation,
      loneliness and a lack of sufficient social and professional support.
      Interventions to reduce caregiver burden should focus on improving social
      support, providing knowledge of heart failure and increasing the perceived
      control over the situation. To date, there is limited research evaluating effects
      of psycho-educational interventions. The few studies that have been conducted
      reported neutral effects, despite having included structured education and
      individualized support as requested by caregivers. There is still a knowledge gap
      on how to fulfill the caregiver's often unmet need for support. Therefore,
      research on developing and evaluating new family-focused interventions is
      warranted. 

PMID- 23857164
TI  - Unusual clinical and molecular-pathological profile of gerstmann-Straussler
      Scheinker disease associated with a novel PRNP mutation (V176G).
AB  - IMPORTANCE: Here we describe the unusual clinical and molecular-neuropathological
      profile of a case of Gerstmann-Straussler-Scheinker disease associated with a
      novel prion protein (PRNP) gene mutation. OBSERVATIONS: This case report from the
      Australian National Creutzfeldt-Jakob Disease Registry concerns a 61-year-old
      British-born woman with no history of neurodegenerative disorder in first-degree
      relatives. Rapidly progressive dementia, altered behavior, and cerebellar ataxia
      dominated the clinical picture in the period immediately following minor elective
      surgery, with death 1 month later in an akinetic-mute state. Brain
      histopathological examination revealed neuronal loss, scant foci of spongiform
      change, and diffuse multicentric amyloid plaques, selectively immunoreactive for
      prion protein, within the cerebral and cerebellar cortices and deep gray matter.
      Tau immune-reactive neurofibrillary tangles and neuritic threads were present in
      the cerebral cortex. PRNP sequencing demonstrated a valine to glycine mutation at
      codon 176, with valine homozygosity at polymorphic codon 129. Western-blot
      analysis of frozen brain tissue displayed a nonclassic protease-resistant prion
      protein banding pattern, with a prominent approximately 8-kDa protease-resistant
      fragment. CONCLUSIONS AND RELEVANCE: Reported is a proband with a novel PRNP
      mutation associated with neuropathologically confirmed Gerstmann-Straussler
      Scheinker disease displaying a somewhat unusual constellation of
      clinicopathological features, which overall subserve to further broaden an
      already diverse phenotypic spectrum.

PMID- 23857165
TI  - Weak grip strength does not predict upper extremity musculoskeletal symptoms or
      injuries among new workers.
AB  - PURPOSE: Grip strength is often tested during post-offer pre-placement screening
      for workers in hand-intensive jobs. The purpose of this study was to evaluate the
      association between grip strength and upper extremity symptoms, work disability,
      and upper extremity musculoskeletal disorders (UE MSDs) in a group of workers
      newly employed in both high and low hand intensive work. METHODS: 1,107 recently
      hired workers completed physical examinations including grip strength
      measurements. Repeated surveys obtained over 3 years described the presence of
      upper extremity symptoms, report of physician-diagnosed musculoskeletal disorders
      (MSDs), and job titles. Baseline measured grip values were used in analytic
      models as continuous and categorized values to predict upper extremity symptoms,
      work disability, or UE MSD diagnosis. RESULTS: Twenty-six percent of males and 20
      % of females had low baseline hand strength compared to normative data.
      Multivariate logistic regression analyses showed no consistent associations
      between grip strength and three health outcomes (UE symptoms, work disability,
      and MSDs) in this young cohort (mean age 30 years). Past MSD and work type were
      significant predictors of these outcomes. CONCLUSIONS: Physical hand strength
      testing was not useful for identifying workers at risk for developing UE MSDs,
      and may be an inappropriate measure for post-offer job screens.

PMID- 23857166
TI  - Variability of microchip capillary electrophoresis with conductivity detection.
AB  - Microfluidic CE with conductivity detection platforms could have an impact on the
      future development of smaller, faster and portable devices. However, for the
      purpose of reliable identification and quantification, there is a need to
      understand the degree of irreproducibility associated with the analytical
      technique. In this study, a protocol was developed to remove baseline drift
      problems sometimes observed in such devices. The protocol, which consisted of pre
      conditioning steps prior to analysis, was used to further assess measurement
      variability from 24 individual microchips fabricated from six separate batches of
      glass substrate. Results show acceptable RSD percentage for retention time
      measurements but large variability in their corresponding peak areas (with some
      microchips having variability of ~50%). Sources of variability were not related
      to substrate batch but possibly to a number of factors such as applied voltage
      fluctuations or variations in microchannel quality, for example surface roughness
      that will subsequently affect microchannel dimensions. 

PMID- 23857167
TI  - Tuning of electronic properties in IV-VI colloidal nanostructures by alloy
      composition and architecture.
AB  - Colloidal lead chalcogenide (IV-VI) quantum dots and rods are of widespread
      scientific and technological interest, owing to their size tunable energy band
      gap at the near-infrared optical regime. This article reviews the development and
      investigation of IV-VI derivatives, consisting of a core (dot or rod) coated with
      an epitaxial shell, when either the core or the shell (or both) has an alloy
      composition, so the entire structure has the chemical formula PbSexS1-x/PbSeyS1-y
      (0 <= x(y) <= 1). The article describes synthesis procedures and an examination
      of the structures' chemical and temperature stability. The investigation of the
      optical properties revealed information about the quantum yield, radiative
      lifetime, emission's Stokes shift and electron-phonon interaction, on the
      variation of composition, core-to-shell division, temperature and environment.
      The study reflected the unique properties of core-shell heterostructures,
      offering fine electronic tuning (at a fixed size) by changing their architecture.
      The optical observations are supported by the electronic band structure
      theoretical model. The challenges related to potential applications of the
      colloidal lead chalcogenide quantum dots and rods are also briefly addressed in
      the article. 

PMID- 23857168
TI  - Effects of pharyngeal water stimulation on swallowing behaviors in healthy
      humans.
AB  - The aims of the present study were to determine whether the interval between
      swallows and the electromyographic (EMG) burst patterns of the suprahyoid muscles
      is affected by peripheral inputs during swallowing. Eighteen normal adults were
      asked to perform repetitive voluntary swallowing as quickly as possible, and
      three variables of swallowing were measured and evaluated, i.e., the swallowing
      intervals and the time interval between the onset and peak (rising time) and
      between the peak and offset (falling time) of the suprahyoid EMG burst. During
      recording, pharyngeal fluid infusion was applied with distilled water or 0.3 M
      NaCl solution at a very slow infusion rate (0.2 mL/min). The former and latter
      were used to activate and inhibit the excitation of water-sensitive receptors in
      the pharynx, respectively. The swallowing interval was significantly shorter
      during infusion of water than during infusion of NaCl solution. The rising time
      was also significantly shorter during infusion of water than during infusion of
      NaCl solution. There was a linear positive correlation between these values and
      facilitatory effects: the longer either the swallowing interval or rising time
      with infusion of 0.3 M NaCl solution, the stronger the facilitation of swallowing
      by the activation of water receptors. Facilitatory effects on the swallowing
      interval and rising time showed a linear correlation. It is suggested that weak
      liquid stimulation changed sensory inputs into the swallowing center and
      synchronously modulated the swallowing interval and time interval between the
      onset and peak of the EMG burst.

PMID- 23857169
TI  - Differential impairment of interhemispheric transmission in bipolar disease.
AB  - There is abundant evidence that the cerebral white matter and in particular the
      corpus callosum show several structural abnormalities in both schizophrenia (SCZ)
      and bipolar disease (BD). However, which cognitive functions are impaired as a
      result of these anomalies is still unclear. Previous behavioural tests of
      interhemispheric crosstalk have shown a differential impairment in SCZ with
      interhemispheric transmission time, as tested with the Poffenberger paradigm,
      essentially normal but with an abnormally enhanced interhemispheric summation
      effect, as tested with the redundant signal effect. The present study was
      inspired by this discrepancy and by the more general question of a possible
      overlap between the pathophysiology of SCZ and BD. We tested both SCZ and BD
      patients in the Poffenberger paradigm and redundant signal effect and found a
      similar dissociation, namely a normal interhemispheric transfer time and an
      abnormal redundant signal effect. The only difference between the two groups was
      a selective slowing of speed of response of the dominant right hand in the SCZ
      group suggesting an impairment of left hemisphere functions. These results cast
      further light on the question of common and differential impairments of basic
      psychological functions in the two diseases.

PMID- 23857171
TI  - How the required precision influences the way we intercept a moving object.
AB  - Do people perform a given motor task differently if it is easy than if it is
      difficult? To find out, we asked subjects to intercept moving virtual targets by
      tapping on them with their fingers. We examined how their behaviour depended on
      the required precision. Everything about the task was the same on all trials
      except the extent to which the fingertip and target had to overlap for the target
      to be considered hit. The target disappeared with a sound if it was hit and
      deflected away from the fingertip if it was missed. In separate sessions, the
      required precision was varied from being quite lenient about the required overlap
      to being very demanding. Requiring a higher precision obviously decreased the
      number of targets that were hit, but it did not reduce the variability in where
      the subjects tapped with respect to the target. Requiring a higher precision
      reduced the systematic deviations from landing at the target centre and the lag
      one autocorrelation in such deviations, presumably because subjects received
      information about smaller deviations from hitting the target centre. We found no
      evidence for lasting effects of training with a certain required precision. All
      the results can be reproduced with a model in which the precision of individual
      movements is independent of the required precision, and in which feedback
      associated with missing the target is used to reduce systematic errors. We
      conclude that people do not approach this motor task differently when it is easy
      than when it is difficult. 

PMID- 23857170
TI  - Left visual field preference for a bimanual grasping task with ecologically valid
      object sizes.
AB  - Grasping using two forelimbs in opposition to one another is evolutionary older
      than the hand with an opposable thumb (Whishaw and Coles in Behav Brain Res
      77:135-148, 1996); yet, the mechanisms for bimanual grasps remain unclear.
      Similar to unimanual grasping, the localization of matching stable grasp points
      on an object is computationally expensive and so it makes sense for the signals
      to converge in a single cortical hemisphere. Indeed, bimanual grasps are faster
      and more accurate in the left visual field, and are disrupted if there is
      transcranial stimulation of the right hemisphere (Le and Niemeier in Exp Brain
      Res 224:263-273, 2013; Le et al. in Cereb Cortex. doi: 10.1093/cercor/bht115,
      2013). However, research so far has tested the right hemisphere dominance based
      on small objects only, which are usually grasped with one hand, whereas bimanual
      grasping is more commonly used for objects that are too big for a single hand.
      Because grasping large objects might involve different neural circuits than
      grasping small objects (Grol et al. in J Neurosci 27:11877-11887, 2007), here we
      tested whether a left visual field/right hemisphere dominance for bimanual
      grasping exists with large and thus more ecologically valid objects or whether
      the right hemisphere dominance is a function of object size. We asked
      participants to fixate to the left or right of an object and to grasp the object
      with the index and middle fingers of both hands. Consistent with previous
      observations, we found that for objects in the left visual field, the maximum
      grip apertures were scaled closer to the object width and were smaller and less
      variable, than for objects in the right visual field. Our results demonstrate
      that bimanual grasping is predominantly controlled by the right hemisphere, even
      in the context of grasping larger objects.

PMID- 23857172
TI  - Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in
      apoB100-only low density lipoprotein (LDL) receptor knockout mice.
AB  - Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride
      (TG) concentrations in humans and mice. We compared mechanisms by which EO and
      fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male
      apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing
      0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO +
      10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester
      (CE) content, which was significantly higher than in FO-fed mice. Plasma TG
      secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein
      (VLDL) particle size was ordered: PO (63 +/- 4 nm) > EO (55 +/- 3 nm) > FO (40 +/
      2 nm). Post-heparin lipolytic activity was similar among groups, but TG
      hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO
      VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally
      faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG
      primarily through increased intravascular lipolysis of TG and VLDL clearance.
      Finally, EO may substitute for FO to reduce plasma TG concentrations, but not
      hepatic steatosis in this mouse model. 

PMID- 23857175
TI  - Determination of chidamide in rat plasma by LC-MS and its application to
      pharmacokinetics study.
AB  - A sensitive and selective liquid chromatography mass spectrometry method for
      determination of chidamide in rat plasma was developed. After addition of
      linezolid as internal standard, protein precipitation by acetonitrile-methanol
      (9:1, v/v) was used as sample preparation. Chromatographic separation was
      achieved on a Zorbax SB-C18 (2.1 * 150 mm, 5 um) column with acetonitrile-0.1%
      formic acid as mobile phase with gradient elution. An electrospray ionization
      source was applied and operated in positive ion mode; selective ion monitoring
      mode was used for quantification using target fragment ions m/z 391.5 for
      chidamide and m/z 338.5 for the IS. Calibration plots were linear over the range
      of 10-2000 ng/mL for chidamide in rat plasma. The lower limit of quantification
      for chidamide was 10 ng/mL. The mean recovery of chidamide in plasma was in the
      range of 86.6-92.1%. The coefficients of variation of intra-day and inter-day
      precision were both <12%. This method is simple and sensitive and was applied
      successfully in a pharmacokinetic study of chidamide to rats.

PMID- 23857174
TI  - Effects of cis-9,trans-11 and trans-10,cis-12 conjugated linoleic acid, linoleic
      acid, phytanic acid and the combination of various fatty acids on proliferation
      and cytokine expression of bovine peripheral blood mononuclear cells.
AB  - Fatty acids may have an impact on immune functions, which is important in times
      of increased mobilization of body fat, e.g., around parturition. The aim of the
      present study was to investigate the effects of the CLA isomers cis-9,trans-11
      and trans-10,cis-12, phytanic acid (PA), linoleic acid (LA) and a fatty acid (FA)
      mixture (containing 29.8% palmitic acid, 6.7% palmitoleic acid, 17.4% stearic
      acid and 46.1% oleic acid) on the proliferation of bovine blood mononuclear cells
      (PBMC) in vitro using alamar blue (AB) and 5-bromo-2'-deoxyuridine (BrdU) assay.
      Quantitative real time polymerase chain reaction analyses were performed to
      evaluate the expression of interleukin (IL)-4, IL-10, interferon (IFN)-gamma,
      tumor necrosis factor (TNF)-alpha and peroxisome proliferator-activated receptor
      (PPAR)-gamma in response to cis-9,trans-11 and LA. The IC50 values did not differ
      between the investigated FA, but there were differences within the proliferation
      in the response of these FA in a concentration range between 20 and 148 uM (e.g.,
      increased proliferation after treatment with lower concentrations of LA). No
      differences occurred when different FA combinations were tested. ConA stimulation
      increased the expression of TNF-alpha and IFN-gamma, whereas IL-10 decreased. In
      general, neither the baseline expression nor the ConA-stimulated mRNA expression
      of cytokines and PPAR-gamma were affected by the FA. In conclusion, all FA
      inhibit the proliferation of PBMC dose dependently without significantly altering
      the induced cytokine spectrum of activated bovine PBMC. 

PMID- 23857176
TI  - Integrase-defective lentiviral vectors as a delivery platform for targeted
      modification of adenosine deaminase locus.
AB  - We investigated the use of integrase-defective lentiviral vectors (IDLVs) for
      transient delivery of zinc finger nucleases (ZFNs) and donor templates for site
      specific modification of the human adenosine deaminase (hADA) gene. Initially, we
      constructed IDLVs carrying ZFN monomers (Single-IDLVs) and found them to be able
      to deliver their gene-editing payload to K562 cells successfully upon
      cotransduction, with minimal cytotoxicity. To simplify delivery, we designed an
      IDLV construct to deliver both ZFN monomers from the same vector (Double-IDLV).
      However, this construct in its original state was prone to rearrangements of the
      vector genome, resulting in greatly reduced functionality; this was due to
      recombination between highly similar ZFN monomers arranged in tandem. We modified
      the Double-IDLV constructs to reduce recombination and restored simultaneous
      delivery of both ZFNs. We also tested an IDLV construct for delivery of donor
      templates and demonstrated its efficacy for gene modification. In summary, we
      highlighted the importance of modifying vector design for co-delivery of highly
      similar sequences inherent to genome-editing nucleases, and demonstrated
      significant improvement in the use of IDLVs for delivery of ZFNs and donor
      templates for genome modification.

PMID- 23857177
TI  - Prostate cancer: should men with metastases undergo radical prostatectomy?

PMID- 23857173
TI  - Vitamin A derivatives as treatment options for retinal degenerative diseases.
AB  - The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans
      retinol, occurring in the outer layer of the human retina and is essential for
      the maintenance of vision. The central source of retinol is derived from dietary
      intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic
      reactions, located in both the photoreceptor outer segment and the retinal
      pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal,
      regenerating visual pigments. Retina specific proteins carry out the majority of
      the visual cycle, and any significant interruption in this sequence of reactions
      is capable of causing varying degrees of blindness. Among these important
      proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment
      epithelium-specific 65-kDa protein (RPE65) known to be responsible for
      esterification of retinol to all-trans-retinyl esters and isomerization of these
      esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are
      identified in human retinal diseases that cause blindness, such as Leber
      congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the
      pathology of 11-cis-retinal deficiency caused by these mutations in both animal
      disease models and human patients. We also review novel therapeutic strategies
      employing artificial visual chromophore 9-cis-retinoids which have been employed
      in clinical trials involving LCA patients. 

PMID- 23857178
TI  - Prostatic fibrosis, lower urinary tract symptoms, and BPH.
AB  - Lower urinary tract symptoms (LUTS)--constituting a spectrum disorder that
      encompasses weak stream, nocturia, and sensations of incomplete emptying and
      intermittent or hesitant urination--are indicative of lower urinary tract
      dysfunction (LUTD). LUTD is a progressive disease that can lead to bladder
      dysfunction if left untreated or treated ineffectively. Sequelae include urinary
      retention, recurrent UTI, bladder calculi, and, eventually, renal impairment.
      LUTD involving the prostate is associated with both ageing and inflammation.
      Tissue inflammation resulting from ageing, infection, or other inflammatory
      disease processes (for example, type 2 diabetes mellitus) is epidemiologically
      associated with the subsequent development of tissue fibrosis in multiple organ
      systems, including the prostate. Recent studies show that tissue fibrosis in the
      lower urinary tract is associated with LUTD, and suggest that fibrosis might be a
      previously unrecognized pathobiology that contributes to LUTD. Thus, antifibrotic
      therapeutic agents should be considered as a new approach to efficaciously
      treating men with LUTD, especially those who don't experience durable responses
      to 5alpha-reductase inhibitors or alpha-adrenergic receptor antagonists.

PMID- 23857179
TI  - Incontinence: novel grafting technique restores bladder function after spinal
      cord transection.

PMID- 23857185
TI  - Focus group discussions in community-based participatory research to inform the
      development of a human papillomavirus (HPV) educational intervention for Latinas
      in San Diego.
AB  - The purpose of this paper is to demonstrate the usefulness of formative focus
      groups as a community-based participatory research (CBPR) method in developing
      cancer education programs. Two focus groups were conducted according to CBPR
      principles, in order to develop a community-competent human papillomavirus
      (HPV)/cervical cancer educational program for Latinas living in the USA/Mexico
      border region. Focus group participants were 18 female Mexican American community
      health advisors. Participants reported that there is limited information and many
      myths about HPV and the vaccine in the Latino/Latina community, along with many
      barriers to acceptance of HPV/cervical cancer-related information. Furthermore,
      participants discussed their recommendations for the development of a culturally
      appropriate HPV educational program. From these data, we have a better
      understanding of the HPV/cervical cancer educational approach that will be most
      accepted in the community and what key information needs to be provided to women
      who participate in the program, which reinforces the importance of the CBPR
      approach to the formative phase of cancer education program development. 

PMID- 23857181
TI  - Cell mates: paracrine and stromal targets for prostate cancer therapy.
AB  - After many years of limited treatment options for patients with metastatic
      castration-resistant prostate cancer (mCRPC), multiple systemic therapies are now
      available, providing patients with significant improvements in survival, symptom
      control and bone health. Most of the recent advances in this area have been based
      on better understanding of mCRPC biology, particularly with respect to the key
      role of androgen receptor signalling. However, most therapies are targeted
      towards the malignant epithelial cell component of the cancer and it should not
      be forgotten that cancer cells exist in close and symbiotic relationships with
      other components of the tumour. Paracrine and stromal signals are often critical
      to the growth of the cancer and represent new potential therapeutic targets that
      are separate from the malignant epithelial cells. The stroma produces numerous
      growth factors, including vascular endothelial growth factor family members,
      platelet-derived growth factors and fibroblast growth factors, which are all
      critical for tumour growth. Targeting prostate-cancer-associated fibroblasts in
      order to destroy the physical and functional scaffold of a cancer is also a
      logical approach. The interaction between prostate cancer and the immune system
      remains an active topic of basic and clinical research, with cytokines,
      chemokines and growth factors being potential targets for therapy. The biology of
      epithelial-mesenchymal transition and of circulating tumour cells might also
      provide insight into new therapeutic targets. 

PMID- 23857187
TI  - An interprofessional web-based approach to providing breast cancer education.
AB  - This paper describes the process that nursing, social work, and pharmacy faculty
      at a state university undertook to develop interprofessional web-based breast
      cancer education modules for incorporation into required curriculum. Eight web
      modules initially developed to educate baccalaureate nursing students on breast
      cancer were revised and expanded at each health professional school to include
      discipline-specific information pertinent to social work and pharmacy scope of
      practice. A specialized internet-accessible web-delivered application was
      constructed consisting of eight reusable learning objects, or modules, including
      epidemiology, risk factors and screening, diagnosis, staging and grading,
      treatment, survivorship, disparities, and metastatic breast cancer. These modules
      were organized for easy integration into existing courses and allowed for an
      efficient means of providing expert, evidence-based content. Innovative methods
      to integrate nursing, social work, and pharmacy education are needed to achieve
      an effective interprofessional educational approach to teaching breast cancer
      content. 

PMID- 23857186
TI  - Metrics for the systematic evaluation of community-based outreach.
AB  - There is an extensive literature on the use of community-based outreach for
      breast health programs. While authors often report that outreach was conducted,
      there is rarely information provided on the effort required for outreach. This
      paper seeks to establish a template for the systematic evaluation of community
      based outreach. We describe three types of outreach used by our project, explain
      our evaluation measures, present data on our outreach efforts, and demonstrate
      how these metrics can be used to inform a project's decisions about which types
      of outreach are most effective. 

PMID- 23857190
TI  - Analysis of boutique arrays: a universal method for the selection of the optimal
      data normalization procedure.
AB  - DNA microarrays, which are among the most popular genomic tools, are widely
      applied in biology and medicine. Boutique arrays, which are small, spotted,
      dedicated microarrays, constitute an inexpensive alternative to whole-genome
      screening methods. The data extracted from each microarray-based experiment must
      be transformed and processed prior to further analysis to eliminate any technical
      bias. The normalization of the data is the most crucial step of microarray data
      pre-processing and this process must be carefully considered as it has a profound
      effect on the results of the analysis. Several normalization algorithms have been
      developed and implemented in data analysis software packages. However, most of
      these methods were designed for whole-genome analysis. In this study, we tested
      13 normalization strategies (ten for double-channel data and three for single
      channel data) available on R Bioconductor and compared their effectiveness in the
      normalization of four boutique array datasets. The results revealed that boutique
      arrays can be successfully normalized using standard methods, but not every
      method is suitable for each dataset. We also suggest a universal seven-step
      workflow that can be applied for the selection of the optimal normalization
      procedure for any boutique array dataset. The described workflow enables the
      evaluation of the investigated normalization methods based on the bias and
      variance values for the control probes, a differential expression analysis and a
      receiver operating characteristic curve analysis. The analysis of each component
      results in a separate ranking of the normalization methods. A combination of the
      ranks obtained from all the normalization procedures facilitates the selection of
      the most appropriate normalization method for the studied dataset and determines
      which methods can be used interchangeably.

PMID- 23857189
TI  - Expression and clinical role of small glutamine-rich tetratricopeptide repeat
      (TPR)-containing protein alpha (SGTA) as a novel cell cycle protein in NSCLC.
AB  - PURPOSE: A small glutamine-rich tetratricopeptide repeat-containing protein alpha
      (SGTA) is a 35 kDa protein involved in a number of biological processes. However,
      the role of SGTA in non-small-cell lung cancer (NSCLC) tumorigenesis has never
      been elucidated. The purpose of this study was to determine whether SGTA could
      serve as a biomarker for stratification and prediction of prognosis in NSCLC.
      METHODS: Small glutamine-rich tetratricopeptide repeat-containing protein alpha
      expression was evaluated by Western blot in 8 paired fresh lung cancer tissues
      and immunohistochemistry on 83 paraffin-embedded sections. The effect of SGTA was
      assessed by RNA interference in A549 cells. Serum starvation and refeeding, flow
      cytometry, CCK-8, and tunnel assays were performed. RESULTS: Small glutamine-rich
      tetratricopeptide repeat-containing protein alpha was highly expressed in NSCLC
      and significantly correlated with NSCLC histological differentiation, clinical
      stage, and Ki-67. Multivariate analysis indicated that SGTA was an independent
      prognostic factor for NSCLC patients' survival. The present investigation
      demonstrated that suppression of SGTA expression resulted in a significant
      decline of proliferation in A549 cells. Besides, SGTA could abolish the toxicity
      of cisplatin in A549 cells. CONCLUSIONS: These findings suggested that SGTA might
      play an important role in promoting the tumorigenesis of NSCLC, and thus be a
      promising therapeutic target to prevent NSCLC progression.

PMID- 23857191
TI  - EBUS-TBNA for the diagnosis of sarcoidosis: is it the only game in town?

PMID- 23857192
TI  - Time for a change.

PMID- 23857193
TI  - Pleural pressure swing and lung expansion after malignant pleural effusion
      drainage: the benefits of high-temporal resolution pleural manometry.
AB  - BACKGROUND: Malignant pleural effusion is a common complication in end-stage
      cancer patients and can cause severe dyspnea. Therapeutic thoracentesis is often
      limited to 1 to 1.5 L. Pleural manometry can be used to recognize a not-expanded
      lung. METHODS: Interval pleural pressure measurements with a high temporal
      resolution were performed after each removal of 200 mL of fluid to observe
      pleural pressure swings. Pleural elastance was defined as the difference in
      pleural pressure divided by the change in volume. Chest x-rays were performed to
      evaluate lung expansion, reexpansion pulmonary edema, and fluid residue. RESULTS:
      Thirty-four procedures in 30 patients were eligible for analysis. Four patients
      had incomplete lung expansion after drainage. No reexpansion pulmonary edema was
      observed. Pleural pressure swing after 200 mL drainage was higher when the lung
      did not expand. Pleural elastance after removal of 500 mL was higher in the not
      expanded subgroup. CONCLUSIONS: We demonstrated that a high pleural pressure
      swing after removal of only 200 mL was related to incomplete lung expansion. We
      confirmed the association between pleural elastance and lung expansion.

PMID- 23857194
TI  - Bronchoscope-induced displacement of lung targets: first in vivo demonstration of
      effect from wedging maneuver in navigated bronchoscopy.
AB  - BACKGROUND: The accuracy of navigated bronchoscopy relies on a best possible
      correlation between the preoperative computed tomography images used for planning
      and the actual tumor position during bronchoscopy. Change in lung structure
      during the procedure may reduce success rate. The size of the lung changes during
      breathing, which may be predicted and at least partly compensated by a navigation
      system. We have studied the effect of the bronchoscopy itself, to see if and how
      the procedure causes further distortions, which might be harder to predict and
      compensate. METHODS: Using newly developed lung tracking sensors, we have
      measured the movement of individual lung segments during a bronchoscopy session
      in pigs. The bronchoscope was moved stepwise forward, ending in a wedge position,
      where it is often positioned when collecting peripheral biopsy specimens during
      conventional bronchoscopy. RESULTS: The influence of the bronchoscope on lung
      segment movement was minimal while positioned in the trachea, main bronchus, or
      lobe bronchus. However, in the wedge position, it displaced the lung targets and
      reduced the natural respiratory motion. CONCLUSIONS: A bronchoscope placed in a
      wedge position displaces lung targets and affects their respiratory behavior. As
      an image navigation system guides the operator towards a position dictated by the
      preoperative computed tomography, the displacement found in this study may cause
      the operator to miss the target. This may be part of the explanation for the
      limited success rates reported in the literature for navigated bronchoscopy.

PMID- 23857195
TI  - Safety and accuracy of semirigid pleuroscopy performed by pulmonary fellows at a
      major university hospital: our initial experience.
AB  - BACKGROUND: Pleuroscopy is considered a safe procedure with a high diagnostic
      accuracy but this record is based on studies published by pulmonologists
      experienced in performing the procedure. METHODS: Review of 40 consecutive
      patients who underwent semirigid pleuroscopy by a pulmonary fellow under the
      supervision of a pulmonologist. RESULTS: Pleuroscopy was performed for diagnosis
      of pleural effusion (n=33), or treatment of pleural effusion (n=4) or
      pneumothorax (n=3). The mean age+/-SD of the patients was 58.23+/-12.98 years and
      23 patients were male. Pleuroscopy was performed with a flex-rigid pleuroscope
      under local anesthesia and conscious sedation. An ultrasound was used to choose
      the entry site. The dose of midazolam and fentanyl used was 6.45+/-2.87 mg and
      173.39+/-77.17 mcg, respectively. The duration of the procedure was 69.3+/-25.3
      minutes. The amount of pleural fluid removed was 1.5+/-0.94 L. The overall
      diagnostic accuracy of pleuroscopy was 87.8%, and the sensitivity, specificity,
      negative and positive predictive value for malignancy was 93.9%, 100%, 92.3% and
      100%, respectively. There were a few complications: desaturation (n=2),
      hypotension (n=5), extensive subcutaneous emphysema (n=3), and persistent air
      leak (n=1). There was no case of significant bleeding or death from the
      procedure. Six of the 7 cardiopulmonary complications occurred during the first 4
      procedures performed by the fellows. CONCLUSIONS: The diagnostic accuracy of
      pleuroscopy remains high in the hands of pulmonary fellows. However, the
      procedure can be associated with a slightly higher rate of complications when
      performed by fellows in training, especially in the early part of their learning
      curve. Most of the few complications observed were not caused by the procedure
      per se and resulted from over-zealous use of medications for conscious sedation.

PMID- 23857196
TI  - The safety of medical thoracoscopy in a group at high risk for complications.
AB  - BACKGROUND: The use of medical thoracoscopy (MT) for the diagnosis and/or
      palliative treatment of pleural effusions is expected to become more widespread
      in the coming years. The aims of the present study were to establish the safety
      of MT in a group of patients at high risk for complications and to determine the
      factors that affect the development of complications. METHODS: A total of 355
      patients who underwent MT were divided into 2 groups: patients at high risk for
      complications and patients who had no risk factor. After the procedure, the
      complications of MT were recorded. All patients were followed up for at least 24
      months. To evaluate the relationship between variables and complications,
      logistic regression models were applied. RESULTS: Of the 355 patients, 106 had
      one or more risk factors, whereas 249 did not have any risk factor. Pain (12.3%)
      was the most frequent complication in the high-risk patients, and subcutaneous
      emphysema (10.3%) was the most frequently reported complication in the normal
      risk patients. Only pain was observed more frequently in the high-risk patients
      compared with the normal-risk patients. Talc pleurodesis was associated with
      prolonged air leak (8.3%) and empyema (5%). The percentage of patients with no
      complication was 58.6%. The mortality rate was 0.28%. In the multivariate
      analysis, the presence of mesothelioma was identified as a factor that increased
      the risk of complication. CONCLUSIONS: MT is a safe method for the diagnosis of
      patients with pleural effusion, even in patients at high risk for complications.
      However, complications, found in approximately half of the patients, should also
      be examined in terms of cost.

PMID- 23857197
TI  - Midazolam in flexible bronchoscopy premedication: effects on patient-related and
      procedure-related outcomes.
AB  - BACKGROUND: The role of midazolam in flexible bronchoscopy premedication has been
      debated. The aim of the present study was to evaluate whether midazolam
      premedication increases the patient-reported tolerance and the physician-reported
      or nurse-reported feasibility of bronchoscopy. METHODS: Randomized, double
      blinded, placebo-controlled, 3-arm study. The study population included patients
      undergoing bronchoscopy for appropriate clinical indications. Patients were
      randomly assigned to receive 0.035 mg/kg intravenous midazolam (low dose), 0.07
      mg/kg (high dose), or placebo. Vital parameters were monitored in continuum
      during the procedure. At the end of the procedure, the operating physician and
      assisting nurse filled out a questionnaire to score the procedure-related
      outcomes (satisfaction, feasibility, completeness, and unexpected events).
      Patients were asked to fill out a specific questionnaire to assess the patient
      reported tolerance and satisfaction 2 hours after the bronchoscopy. RESULTS: A
      total of 100 patients (mean age 58.6+/-1.0; 57% male) were included in the study
      (33 in the low-dose midazolam group, 34 in the high-dose midazolam group, and 33
      in the placebo group). The patient-reported tolerance score was significantly
      higher in the high-dose midazolam group than in the placebo group (P<0.01). No
      differences were found in the 3 groups in terms of the physician-reported
      feasibility and completeness of the procedure. In the groups of patients
      premedicated with midazolam, significant oxygen desaturation was recorded (at 10
      and 8 min after the introduction of the bronchoscope) compared with the baseline
      value (P<0.01). CONCLUSIONS: In our study, premedication with midazolam increased
      the patient-reported tolerance of the bronchoscopy. However, the absence of
      premedication did not affect the diagnostic yield of the procedure.

PMID- 23857198
TI  - Methemoglobinemia in bronchoscopy: a case series and a review of the literature.
AB  - BACKGROUND: Methemoglobinemia results from oxidation of ferrous iron to ferric
      iron within the hemoglobin molecule. This molecule cannot bind oxygen and
      increases the affinity of normal hemoglobin for oxygen, which results in
      decreased oxygen offloading in peripheral tissues. At elevated levels,
      methemoglobinemia can cause dyspnea, cyanosis, and even death. Common local
      anesthesia agents have been correlated with methemoglobinemia. Bronchoscopy is a
      commonly performed clinical procedure which uses topical application of these
      anesthetics to provide patient comfort. Methylene blue is an agent thought to
      help reverse the effects of methemoglobinemia by facilitating the methemoglobin
      reductase system. METHODS: Using multiple search engines including PubMed and the
      Cochrane Database, available data on cases of methemoglobinemia after
      bronchoscopy were pooled. Adult and pediatric cases were considered. RESULTS:
      Eleven cases were identified. Cases occurred from 1977 until present. Data
      gathering was complicated by the fact that a consistent reporting system was not
      used across cases. Arterial blood gas data and CO-oximetry reported levels of
      methemoglobin were reported where available. No patients died from
      methemoglobinemia. The most common finding across all patients was decreased
      peripheral oxygen saturation. Cyanosis was also frequently reported. There was a
      disparity between the low peripheral oxygen saturation which was reported and the
      pO(2) on the arterial blood gas. Dose and type of anesthetic agent varied widely
      across studies. CONCLUSIONS: Using topical anesthetic during bronchoscopy appears
      relatively safe. No fatalities from methemoglobinemia after bronchoscopy have
      been reported. A high suspicion for methemoglobinemia is required in patients who
      develop hypoxia or cyanosis postprocedurally. Access to CO-oximetry can confirm
      the diagnosis but the clinical picture is often sufficient to proceed with
      methylene blue treatment or observation, based on how severely the patient is
      affected. Patients who return to baseline can be considered for discharge home.

PMID- 23857199
TI  - Endobronchial hamartoma.
AB  - We present images of an endobronchial hamartoma visible by bronchoscopy in the
      left lower lobe. A 56-year-old woman with a late presentation of an acute
      anterior myocardial infarction requires urgent heart transplantation and
      subsequently has trouble weaning off the ventilator. Bronchoscopic evaluation
      reveals a 1 cm endobronchial hamartoma obstruction the left lower lobe bronchus.
      A polypectomy snare was effectively used with electrocautery to excise the
      lesion. The patient was successfully able to wean off the ventilator once the
      left lower lobe was free from obstruction.

PMID- 23857200
TI  - Role of narrowband imaging in assessing endobronchial cryptococcosis.
AB  - Endobronchial cryptococcosis can cause tracheobronchitis with granulomatous
      changes. In this patient under steroid therapy, bronchoscopic images revealed
      elevated white patchy lesion on the posterior longitudinal folds of the lower
      trachea. Bronchoscopy with narrowband imaging (NBI) revealed opaque bronchial
      subepithelial vessels. Endobronchial biopsy confirmed Cryptococcus neoformans
      infection in the subepithelial layer. Following treatment with fluconazole,
      bronchoscopy with NBI revealed the disappearance of elevated lesion and regrowth
      of vessels of regular caliber. NBI might be useful to assess and follow-up
      endobronchial fungal infection and other inflammatory processes. 

PMID- 23857201
TI  - Needle assembly malfunction: an unusual complication related to endobronchial
      ultrasound-guided transbronchial needle aspiration.
AB  - Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration has
      become an invaluable tool for thoracic physicians. Along with medical
      complications, it is also important to understand the equipment-related
      malfunctions. The EBUS scope is delicate and requires dedicated needle assembly
      for performing the needle aspirates. EBUS scope damage could be expensive and has
      been well described. We report 2 rare cases of Olympus EBUS needle assembly
      malfunction (model NA-201SX-4021/4022). The first case describes needle breakage
      and the second case reports the separation of shaft of sheath-sliding mechanism. 

PMID- 23857202
TI  - Endobronchial inflammatory pseudotumor: a rare cause of a pneumothorax in
      children.
AB  - Inflammatory pseudotumors of the lung are a group of non-neoplastic tumors, which
      are mainly of parenchymal origin and rarely endobronchial. We report a case of a
      9-year-old girl who presented with left-sided tension pneumothorax and
      subcutaneous emphysema. After emergency management, chest computed tomography
      revealed an ill-defined left lung mass. Rigid bronchoscopy revealed a mass
      occluding the left main bronchus at the origin of the left upper lobe bronchus.
      Initially, the mass was thought to be a foreign body granuloma. Few weeks later,
      the child presented with recurrence of the same clinical, radiologic, and
      bronchoscopic outcomes. Histologic examination after the repeat bronchoscopic
      excision revealed the lesion to be consistent with inflammatory pseudotumor. Left
      upper lobectomy was performed with a complete resolution of symptoms and no
      recurrence was observed during the 2 years of follow-up. To the best of our
      knowledge, this is the first reported case of inflammatory pseudotumor presenting
      with tension pneumothorax. 

PMID- 23857203
TI  - Tracheobronchial amyloidosis in a patient with Sjogren syndrome.
AB  - Pulmonary amyloidosis in the setting of Sjogren syndrome is rare. It most
      commonly presents in form of multinodular disease with or without cysts
      formation. Amyloid plaques may also deposit in the airway submucosa, causing
      airway narrowing; the condition referred as "tracheobronchial amyloidosis" (TBA).
      Patients with this condition most commonly present with postobstructive
      pneumonia, wheezing, and occasionally hemoptysis. Endoscopic therapies, using
      flexible forceps with or without laser therapy is crucial to alleviate the
      obstruction and control the bleeding. Other therapeutic modalities such as
      external beam radiation has been shown to be promising; however, further data are
      still needed. To our knowledge, our patient is the first reported case of TBA in
      a setting of Sjogren syndrome. 

PMID- 23857204
TI  - The microbiology of postobstructive pneumonia in lung cancer patients.
AB  - Recurrent pneumonias often occur in the setting of an airway obstruction and can
      be the presenting symptom of an undiagnosed malignancy. Little is known regarding
      the microbiology of these pneumonias making antibiotic therapy difficult to
      direct; however, the few studies available show these pneumonias to be
      polymicrobial. Examining the colonization patterns of at-risk populations such as
      patients with chronic obstructive pulmonary disease and using techniques such as
      ultrasound and computed tomography-guided biopsies may help in the treatment of
      these pneumonias. The following review is presented to highlight the current
      medical knowledge as well as suggest areas for future evaluation. 

PMID- 23857205
TI  - "The black bronchoscopy": a case of airway soot deposition.
AB  - The term "black bronchoscopy" is used to describe the black pigmentation of the
      airways. It is a rare condition with multiple etiologies. We describe a case of a
      "black bronchoscopy" due to severe soot deposition as a result of smoke
      inhalation during a household fire in a 71-year-old woman. Early flexible
      bronchoscopy allowed for a precise diagnosis of severe inhalation injury, and
      bronchial lavage was carried out to remove soot casts to reduce complications.
      Any patient suspected of having smoke inhalation injury should undergo early
      bronchoscopy to allow for a precise diagnosis, staging, and more aggressive
      treatment measures as the mortality among patients exposed to smoke with
      inhalation airway injury is high. 

PMID- 23857206
TI  - Endobronchial fiducial to guide stereotactic body radiotherapy.
AB  - Optimal treatment for unresectable central airway tumors is not well established.
      Stereotactic body radiation therapy has shown efficacy for both peripheral and
      central lung lesions. However, the treatment of central tumors has been limited
      because of associated radiation toxicity. We report the use of an endobronchial
      fiducial to localize hypofractionated stereotactic body radiation therapy
      treatment of a limited central airways disease in a patient with recurrent
      metastatic squamous cell lung cancer. The fiducial was instrumental in designing
      the treatment field and minimizing related treatment toxicity. Future studies may
      take advantage of this technique in patients with unresectable central airways
      non-small cell lung cancers. 

PMID- 23857207
TI  - A case of massive airway clotting after use of activated factor VII for massive
      hemoptysis: management with flexible bronchoscopy and cryoadhesion.
AB  - This case describes the use of flexible bronchoscopy and cryoadhesion in an 83
      year-old man who developed large airway clots following treatment with activated
      factor VII for a complication of pulmonary hemorrhage during coronary artery
      bypass graft. 

PMID- 23857208
TI  - Use of linear EBUS in work-up of a pulmonary nodule.
AB  - Diagnostic approach to a pulmonary nodule depends upon the characteristics of the
      nodule and its location. Despite utilizing advanced minimally invasive diagnostic
      techniques, the work-up might be challenging. We report the case of a 60-year-old
      woman with history of breast cancer that was treated with lumpectomy 11 years
      earlier. She presented with a pulmonary nodule located medially in the fissure
      between the left upper and lower lobes. Linear EBUS was chosen as a diagnostic
      approach and the diagnosis of metastatic breast cancer was made without any
      complications. This case highlights the potential use of linear EBUS in centrally
      located pulmonary nodules or masses. 

PMID- 23857209
TI  - Therapeutic bronchoscopy followed by lobectomy for pulmonary sarcoma.
AB  - Malignant central airway obstruction is a life-threatening presentation requiring
      emergency palliative procedure. In selected patients, bronchoscopic intervention
      could be used as a bridge to curative resection. Here we report a 54-year-old
      male with pulmonary sarcoma of the right upper lobe, presenting with acute
      respiratory failure because of endobronchial extension. Emergency coring with the
      rigid bronchoscope and Dumon stent insertion stabilized the patient, and
      subsequent lobectomy resulted in occurrence-free survival over a 71-month follow
      up. 

PMID- 23857210
TI  - Tracheal ring fracture and pseudomembrane formation after percutaneous
      dilatational tracheostomy.

PMID- 23857211
TI  - A remedy for hoarseness in a patient with granulomatosis with polyangiitis.

PMID- 23857212
TI  - A leaking esophagus and a nonbreathing bag: new signs of airway-esophageal
      connection.

PMID- 23857213
TI  - Repair of a full-thickness tracheal tear using cardiopulmonary bypass.

PMID- 23857215
TI  - CD10 is frequently expressed in classical seminomas.
AB  - CD10 is a cell surface metalloproteinase widely expressed in various normal
      tissue and in epithelial, stromal or both components of various malignancies. The
      aim of our study was to investigate, for the first time, the expression of CD10
      in a series of 135 cases of testicular germ cell tumours in order to asses its
      possible diagnostic and biologic significance. The expression of CD10 was
      studied, using immunohistochemistry, in 96 pure forms and 39 mixed forms of
      germinal cell tumours of the testis. Immunostaining for CD10 was positive in
      68/74 (92%) seminomas and 16/24 (67%) seminomatous component of mixed germ cell
      tumours. The intratubular germ cell neoplasia of the unclassified type always
      expressed CD10. Anaplastic seminomas, embryonal carcinomas, teratoma and
      spermatocytic seminomas were negative for CD10. Our findings indicate that only
      seminomas and intratubular germ cell neoplasia, the precursors of germ cell
      tumours, express CD10, but when they differentiate along embryonal, somatic,
      trophoblastic, yolk sac lines they lose CD10 expression. CD10 could be considered
      a useful marker to differentiate seminoma from other forms of testicular germ
      cell tumours and for a better estimation of the seminomatous component in mixed
      germ cell tumours.

PMID- 23857214
TI  - Pelvic pain and papillary thyroid carcinoma: case report.
AB  - Usually differentiated thyroid cancer has a good prognosis and only rarely shows
      distant metastasis at diagnosis above all the papillary carcinoma. We present the
      case of a female patient of 66 years old affected by a papillary thyroid
      carcinoma with a bone metastasis as initial presenting symptom; she was
      hospitalized for pelvic pain and motor weakness and treated for severe
      osteoporosis. The patient was submitted to pelvis X-Ray that showed an area of
      bone loss and cortical irregularities of the right acetabulum, which was
      compatible with secondary neoplastic lesion but no primary tumor was found. The
      bone biopsy showed "papillary thyroid carcinoma, follicular variant", so the
      patient was candidated to a total thyroidectomy.

PMID- 23857217
TI  - Calcidiol deficiency in end-stage organ failure and after solid organ
      transplantation: status quo.
AB  - Among patients with organ failure, vitamin D deficiency is extremely common and
      frequently does not resolve after transplantation. This review crystallizes and
      summarizes existing data on the status quo of vitamin D deficiency in patients
      with organ failure and in solid organ transplant recipients. Interventional
      studies evaluating different treatment strategies, as well as current clinical
      practice guidelines and recommendations on the management of low vitamin D status
      in these patients are also discussed. 

PMID- 23857218
TI  - Effect of ethyl pyruvate on skeletal muscle metabolism in rats fed on a high fat
      diet.
AB  - Impaired mitochondrial capacity may be implicated in the pathology of chronic
      metabolic diseases. To elucidate the effect of ethyl pyruvate supplementation on
      skeletal muscles metabolism we examined changes in activities of mitochondrial
      and antioxidant enzymes, as well as sulfhydryl groups oxidation (an indirect
      marker of oxidative stress) during the development of obesity. After 6 weeks
      feeding of control or high fat diet, Wistar rats were divided into four groups:
      control diet, control diet and ethyl pyruvate, high fat diet, and high fat diet
      and ethyl pyruvate. Ethyl pyruvate was administered as 0.3% solution in drinking
      water, for the following 6 weeks. High fat diet feeding induced the increase of
      activities 3-hydroxyacylCoA dehydrogenase, citrate synthase, and fumarase.
      Moreover, higher catalase and superoxide dismutase activities, as well as
      sulfhydryl groups oxidation, were noted. Ethyl pyruvate supplementation did not
      affect the mitochondrial enzymes' activities, but induced superoxide dismutase
      activity and sulfhydryl groups oxidation. All of the changes were observed in
      soleus muscle, but not in extensor digitorum longus muscle. Additionally,
      positive correlations between fasting blood insulin concentration and activities
      of catalase (p = 0.04), and superoxide dismutase (p = 0.01) in soleus muscle were
      noticed. Prolonged ethyl pyruvate consumption elevated insulin concentration,
      which may cause modifications in oxidative type skeletal muscles. 

PMID- 23857219
TI  - Iron: protector or risk factor for cardiovascular disease? Still controversial.
AB  - Iron is the second most abundant metal in the Earth's crust. Despite being
      present in trace amounts, it is an essential trace element for the human body,
      although it can also be toxic due to oxidative stress generation by the Fenton
      reaction, causing organic biomolecule oxidation. This process is the basis of
      numerous pathologies, including cardiovascular diseases (CVD). The relationship
      between iron and cardiovascular disease was proposed in 1981 by Jerome Sullivan.
      Since then, numerous epidemiological studies have been conducted to test this
      hypothesis. The aim of this review is to present the main findings of the chief
      epidemiological studies published during the last 32 years, since Sullivan
      formulated his iron hypothesis, suggesting that this element might act as a risk
      factor for cardiovascular disease. We have analyzed 55 studies, of which 27
      supported the iron hypothesis, 20 found no evidence to support it and eight were
      contrary to the iron hypothesis. Our results suggest that there is not a high
      level of evidence which supports the hypothesis that the iron may be associated
      with CVD. Despite the large number of studies published to date, the role of iron
      in cardiovascular disease still generates a fair amount of debate, due to a
      marked disparity in results. 

PMID- 23857220
TI  - A population model of folate-mediated one-carbon metabolism.
AB  - BACKGROUND: Previous mathematical models for hepatic and tissue one-carbon
      metabolism have been combined and extended to include a blood plasma compartment.
      We use this model to study how the concentrations of metabolites that can be
      measured in the plasma are related to their respective intracellular
      concentrations. METHODS: The model consists of a set of ordinary differential
      equations, one for each metabolite in each compartment, and kinetic equations for
      metabolism and for transport between compartments. The model was validated by
      comparison to a variety of experimental data such as the methionine load test and
      variation in folate intake. We further extended this model by introducing random
      and systematic variation in enzyme activity. OUTCOMES AND CONCLUSIONS: A database
      of 10,000 virtual individuals was generated, each with a quantitatively different
      one-carbon metabolism. Our population has distributions of folate and
      homocysteine in the plasma and tissues that are similar to those found in the
      NHANES data. The model reproduces many other sets of clinical data. We show that
      tissue and plasma folate is highly correlated, but liver and plasma folate much
      less so. Oxidative stress increases the plasma S-adenosylmethionine/S
      adenosylhomocysteine (SAM/SAH) ratio. We show that many relationships among
      variables are nonlinear and in many cases we provide explanations. Sampling of
      subpopulations produces dramatically different apparent associations among
      variables. The model can be used to simulate populations with polymorphisms in
      genes for folate metabolism and variations in dietary input.

PMID- 23857221
TI  - Metformin lowers serum cobalamin without changing other markers of cobalamin
      status: a study on women with polycystic ovary syndrome.
AB  - Treatment with the anti-diabetic drug metformin is followed by a decline in
      plasma cobalamin, but it is unsettled whether this denotes an impaired cobalamin
      status. This study has explored changes in the markers of cobalamin status in
      women with Polycystic Ovary Syndrome treated with metformin (1.5-2.5 g per day)
      (n = 29) or placebo (n = 23) for six months. Serum samples were collected before
      and after two, four, and six months of treatment. We found serum cobalamin to
      decline and reach significant lower levels after six months of treatment (p =
      0.003). Despite the decline in serum cobalamin, we observed no reductions in the
      physiological active part of cobalamin bound to transcobalamin
      (holotranscobalamin), or increase in the metabolic marker of cobalamin status,
      methylmalonic acid. Instead, the non-functional part of circulating cobalamin
      bound to haptocorrin declined (p = 0.0009). Our results have two implications:
      The data questions whether metformin treatment induces an impaired cobalamin
      status in PCOS patients, and further suggests that serum cobalamin is a futile
      marker for judging cobalamin status in metformin-treated patients. 

PMID- 23857222
TI  - Eye nutrition in context: mechanisms, implementation, and future directions.
AB  - Carotenoid-based visual cues and roles of carotenoids in human vision are
      reviewed, with an emphasis on protection by zeaxanthin and lutein against vision
      loss, and dietary sources of zeaxanthin and lutein are summarized. In addition,
      attention is given to synergistic interactions of zeaxanthin and lutein with
      other dietary factors affecting human vision (such as antioxidant vitamins,
      phenolics, and poly-unsaturated fatty acids) and the emerging mechanisms of these
      interactions. Emphasis is given to lipid oxidation products serving as messengers
      with functions in gene regulation. Lastly, the photo-physics of light collection
      and photoprotection in photosynthesis and vision are compared and their common
      principles identified as possible targets of future research. 

PMID- 23857224
TI  - Cardiovascular effects of calcium supplements.
AB  - Calcium supplements reduce bone turnover and slow the rate of bone loss. However,
      few studies have demonstrated reduced fracture incidence with calcium
      supplements, and meta-analyses show only a 10% decrease in fractures, which is of
      borderline statistical and clinical significance. Trials in normal older women
      and in patients with renal impairment suggest that calcium supplements increase
      the risk of cardiovascular disease. To further assess their safety, we recently
      conducted a meta-analysis of trials of calcium supplements, and found a 27%-31%
      increase in risk of myocardial infarction, and a 12%-20% increase in risk of
      stroke. These findings are robust because they are based on pre-specified
      analyses of randomized, placebo-controlled trials and are consistent across the
      trials. Co-administration of vitamin D with calcium does not lessen these adverse
      effects. The increased cardiovascular risk with calcium supplements is consistent
      with epidemiological data relating higher circulating calcium concentrations to
      cardiovascular disease in normal populations. There are several possible
      pathophysiological mechanisms for these effects, including effects on vascular
      calcification, vascular cells, blood coagulation and calcium-sensing receptors.
      Thus, the non-skeletal risks of calcium supplements appear to outweigh any
      skeletal benefits, and are they appear to be unnecessary for the efficacy of
      other osteoporosis treatments. 

PMID- 23857223
TI  - Vitamin D and immune function.
AB  - Vitamin D metabolizing enzymes and vitamin D receptors are present in many cell
      types including various immune cells such as antigen-presenting-cells, T cells, B
      cells and monocytes. In vitro data show that, in addition to modulating innate
      immune cells, vitamin D also promotes a more tolerogenic immunological status. In
      vivo data from animals and from human vitamin D supplementation studies have
      shown beneficial effects of vitamin D on immune function, in particular in the
      context of autoimmunity. In this review, currently available data are summarized
      to give an overview of the effects of vitamin D on the immune system in general
      and on the regulation of inflammatory responses, as well as regulatory mechanisms
      connected to autoimmune diseases particularly in type 1 diabetes mellitus. 

PMID- 23857226
TI  - The reduced folate carrier (RFC-1) 80A>G polymorphism and maternal risk of having
      a child with Down syndrome: a meta-analysis.
AB  - A common polymorphism (c.80A>G) in the gene coding for the reduced folate carrier
      (SLC19A1, commonly known as RFC-1) has been associated with maternal risk of the
      birth of a child with Down Syndrome (DS), but results are controversial. We
      searched major online databases to identify available case-control studies, and
      performed a meta-analysis to summarize the data concerning this association. Nine
      independent case-control studies were identified for a total of 930 DS mothers
      (MDS) and 1240 control mothers. Odds ratios (OR) and 95% confidence intervals
      (CI) were calculated using both fixed and random effects models. An increase in
      the risk of having a birth with DS was observed for carriers of the homozygous GG
      genotype (OR 1.27, 95% CI 1.04-1.57; p = 0.02, fixed effects model), even after
      removal from the meta-analysis of published data with deviations from Hardy
      Weinberg equilibrium (HWE) in controls (OR 1.26, 95% CI 1.02-1.55; p = 0.03,
      fixed effects model). Moreover, the pooled OR under the fixed effects model
      showed an increase in the maternal risk for the G allele (OR 1.14, 95% CI 1.01
      1.30; p = 0.03). Present results suggest that the maternal RFC-1 80A>G
      polymorphism might be associated with an increased risk of having a birth with
      DS, particularly among carriers of the GG genotype. 

PMID- 23857225
TI  - The use of probiotic strains in caries prevention: a systematic review.
AB  - This paper aims to provide a systematic review of the caries-prevention effect of
      probiotics in human. The hypothesis was that the administration of probiotic
      strains might play a role in caries lesion prevention and in the control of
      caries-related risk factors. The main relevant databases (Medline, Embase) were
      searched. Quality of the Randomized Clinical Trials (RCTs) was classified using
      the "Consolidated Standards of Reporting Trials" (CONSORT) checklist and the
      Impact Factor (IF) value of each journal was recorded. Sixty-six papers were
      identified, and 23 fulfilled the inclusion criteria. Only three studies had
      caries lesion development as outcome, all the others reported caries risk factors
      as interim evaluation. Using the CONSORT Score, the papers were coded as 4
      excellent, 9 good and 10 poor. The mean IF value recorded was 1.438. Probiotics
      may play a role as antagonistic agent on mutans streptococci (MS),
      acidogenic/aciduric bacteria that contributes to the caries process. In two
      thirds of the selected papers, probiotics have demonstrated the capacity to
      reduce MS counts in saliva and/or plaque in short-term. The effect of probiotics
      on the development of caries lesion seems encouraging, but to date, RCTs on this
      topic are insufficient to provide scientific clinical evidence. 

PMID- 23857227
TI  - Chemopreventive potential of flavonoids in oral squamous cell carcinoma in human
      studies.
AB  - Evidence available from nutritional epidemiology has indicated an inverse
      association between regular consumption of fruits and vegetables and the risk of
      developing certain types of cancer. In turn, preclinical studies have attributed
      the health-promoting effects of plant foods to some groups of phytochemicals, by
      virtue of their many biological activities. In this survey, we briefly examine
      the chemopreventive potential of flavonoids and flavonoid-rich foods in human
      oral carcinogenesis. Despite the paucity of data from clinical trials and
      epidemiological studies, in comparison to in vitro/in vivo investigations, a high
      level of evidence has been reported for epigallocatechin gallate (EGCG) and
      anthocyanins. These flavonoids, abundant in green tea and black raspberries,
      respectively, represent promising chemopreventive agents in human oral cancer. 

PMID- 23857229
TI  - Kernohan-woltman notch phenomenon in acute subdural hematoma.

PMID- 23857228
TI  - A novel role for a major component of the vitamin D axis: vitamin D binding
      protein-derived macrophage activating factor induces human breast cancer cell
      apoptosis through stimulation of macrophages.
AB  - The role of vitamin D in maintaining health appears greater than originally
      thought, and the concept of the vitamin D axis underlines the complexity of the
      biological events controlled by biologically active vitamin D (1,25(OH)(2)D3),
      its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D
      binding protein-derived macrophage activating factor (GcMAF). In this study we
      demonstrate that GcMAF stimulates macrophages, which in turn attack human breast
      cancer cells, induce their apoptosis and eventually phagocytize them. These
      results are consistent with the observation that macrophages infiltrated
      implanted tumors in mice after GcMAF injections. In addition, we hypothesize that
      the last 23 hydrophobic amino acids of VDR, located at the inner part of the
      plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF
      located at the external part of the plasma membrane. This allows 1,25(OH)(2)D3
      and oleic acid to become sandwiched between the two vitamin D-binding proteins,
      thus postulating a novel molecular mode of interaction between GcMAF and VDR.
      Taken together, these results support and reinforce the hypothesis that GcMAF has
      multiple biological activities that could be responsible for its anti-cancer
      effects, possibly through molecular interaction with the VDR that in turn is
      responsible for a multitude of non-genomic as well as genomic effects.

PMID- 23857232
TI  - Social media and community engagement in trials using exception from informed
      consent.

PMID- 23857231
TI  - Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II
      epitopes.
AB  - Immune responses directed against viral capsid proteins constitute a main safety
      concern in the use of adeno-associated virus (AAV) as gene transfer vectors in
      humans. Pharmacological immunosuppression has been proposed as a solution to the
      problem; however, the approach suffers from several potential limitations. Using
      MHC class II epitopes initially identified within human IgG, named Tregitopes, we
      showed that it is possible to modulate CD8+ T cell responses to several viral
      antigens in vitro. We showed that incubation of peripheral blood mononuclear
      cells with these epitopes triggers proliferation of CD4+CD25+FoxP3+ T cells that
      suppress killing of target cells loaded with MHC class I antigens in an antigen
      specific fashion, through a mechanism that seems to require cell-to-cell contact.
      Expression of a construct encoding for the AAV capsid structural protein fused to
      Tregitopes resulted in reduction of CD8+ T cell reactivity against the AAV capsid
      following immunization with an adenoviral vector expressing capsid. This was
      accompanied by an increase in frequency of CD4+CD25+FoxP3+ T cells in spleens and
      lower levels of inflammatory infiltrates in injected tissues. This proof-of
      concept study demonstrates modulation of CD8+ T cell reactivity to an antigen
      using regulatory T cell epitopes is possible.

PMID- 23857233
TI  - Preliminary experience with social media for community consultation and public
      disclosure in exception from informed consent trials.

PMID- 23857234
TI  - Chest pain and palpitations: taking a closer look.
AB  - This case highlights the importance of considering a wide differential diagnosis
      in a young patient with chest pain and an abnormal ECG. Rarer causes of
      myocarditis such as GCM should be sought in patients who develop ventricular
      arrhythmias or high-grade heart block because the treatment is different and
      dramatically influences outcome. Our patient is the first reported case of GCM
      and a concurrent diagnosis of tuberculosis. It is most likely that the
      histological appearance of GCM was due to the presence of mycobacterial infection
      within the myocardium, and we believe that effective antituberculous therapy has
      led to resolution of the GCM without the need for continued long-term
      immunosuppression.

PMID- 23857236
TI  - Fever of unknown origin with angina: an atypical presentation of polyangiitis
      with granulomatosis.

PMID- 23857237
TI  - Entrapment of the left anterior descending coronary artery by localized calcific
      pericarditis: from dynamic to fixed coronary stenosis.

PMID- 23857239
TI  - Letter by Gomez-Ambrosi et al regarding article, "clinical assessment and
      management of adult obesity".

PMID- 23857240
TI  - Letter by Santovito et al regarding article, "rhythm versus rate control therapy
      and subsequent stroke or transient ischemic attack in patients with atrial
      fibrillation".

PMID- 23857241
TI  - Letter by Gasparovic and Kopjar regarding article, "rhythm versus rate control
      therapy and subsequent stroke or transient ischemic attack in patients with
      atrial fibrillation".

PMID- 23857242
TI  - Letter by Parikh and Rashba regarding article, "rhythm versus rate control
      therapy and subsequent stroke or transient ischemic attack in patients with
      atrial fibrillation".

PMID- 23857243
TI  - Values and depressive symptoms in American Indian youth of the Northern Plains:
      examining the potential moderating roles of outcome expectancies and perceived
      community values.
AB  - Very little is known about processes contributing to depressive experiences in
      American Indian youth. We explored the relationship between value priorities and
      depressive symptoms among 183 (65% female) American Indian youth in grades 9-12.
      In addition, two potential moderators of this relationship were examined: value
      outcome expectations (i.e., whether one expects that values will be realized or
      not) and perceived community values. We found that American Indian youth who
      endorsed higher levels of tradition/benevolence values reported fewer depressive
      symptoms. However, the relationship between endorsing power/materialism values
      and depressive symptoms depended on the extent to which youth perceived their
      communities as valuing power/materialism. Finally, value outcome expectancies
      appeared to relate more strongly to depressive symptoms than did value
      priorities. Overall, these findings support tribal community efforts to impart
      tradition/benevolence values to American Indian youth but also emphasize the
      importance of attending to value outcome expectations and the perceived values of
      the community in understanding American Indian youth's depressive experiences.

PMID- 23857244
TI  - Quantitative analysis of thymosin beta4 in whole saliva by capillary
      electrophoresis-mass spectrometry using multiple ions monitoring (CE-MIM-MS.).
AB  - Thymosin beta4 (Tbeta4) is a peptide present in almost any tissue and in
      extracellular media in mammals, having multiple amazing functions as wound
      healing, stimulation of angiogenesis, and suppression of inflammation. This study
      describes its determination in saliva through CE-MS using multiple ions
      monitoring scan mode by isolating the four most intense multicharged ions present
      in the MS spectra of the peptide. This scan modality, by reducing the baseline
      noise and interferences, increases the sensitivity and specificity in biological
      matrices. The CE-MS separation was optimized by studying different parameters
      influencing CE analysis, sample injection, and MS ionization, that is, the
      nebulizer gas flow, the sheath liquid, and BGE composition. The proposed
      technique can unambiguously identify in short time Tbeta4 in saliva after a very
      fast and reduced sample pretreatment procedure. The method was validated for
      quantitation showing linearity of the response in the range 0.25 (lower limit of
      quantification) to 4 MUM (average R2 0.996 +/- 0.005) and intra- and interassay
      precision and accuracy at three different concentrations with RSD values in the
      range of 7-16%. It was successfully applied to the analysis of Tbeta4 in whole
      saliva showing a variable peptide content from individual to individual (in the
      range of 0.3-1.4 MUM) and in different days from the same individual. CE-MS in
      multiple ions monitoring scan mode provides a fast, selective, and economic
      method requiring only very few microliters of sample.

PMID- 23857245
TI  - Joint ESR-EFSUMB recommendation on archiving and reporting ultrasound
      examinations.
AB  - BACKGROUND: The ESR and EFSUMB have issued a joint statement about the necessity
      of a formal report for all ultrasonographic examinations as well as proper
      archiving of both reports and images within hospital information technology (IT)
      systems. Both societies agreed on the importance of availability of US images and
      reports in clinical practice and agreed on a formal recommendation to their
      members on this topic. MAIN MESSAGES: * Availability of reports and images of all
      US examinations is important in clinical practice as a record of patient status
      at the time of the studies and as a point of references for future studies, with
      either US or other imaging modalities. * Both ESR and EFSUMB consider it good
      clinical practice to provide accurate and retrievable recordings of all
      ultrasonographic examinations. * Both ESR and EFSUMB recommend to their members
      to organise workflow in ultrasonography so that proper archiving of both images
      and reports of all studies can be regularly obtained.

PMID- 23857246
TI  - [Karl Alfons Portele, Pathologist and first director of the Federal Pathologic
      anatomical Museum Vienna].
AB  - The importance of the work of Karl Alfons Portele (1912-1993) in his position as
      director of the Federal Museum of Pathology is discussed. Portele was
      commissioned with the museum in 1946 and separated it from university in 1974.
      The history of the Pathologic-anatomical Museum in Vienna is closely connected
      with the history of pathology. 

PMID- 23857247
TI  - [Forensic aspects of gunshot suicides in Germany].
AB  - Suicidal gunshot wounds are a common appearance in forensic casework. The main
      task of the coroner lies in the detection of typical pathomorphological
      correlates, thus differentiating between homicide, suicide and accident. Apart
      from characteristic bloodstain patterns on the gun and shooting hand, the
      localisation of the entrance wound and the position of the weapon, additional
      details such as family background or medical history are important aspects of
      forensic investigation. An uncommon choice of weaponry and its unusual
      morphological manifestation often complicate the examination and reconstruction
      of such cases. Furthermore, due to social stigmatisation, the possibility of
      secondary changes by relatives at the crime scene should be considered. In
      addition to autopsy findings, a careful crime scene investigation and bloodstain
      pattern analysis, a ballistic reconstruction can be an essential tool to gain
      knowledge of the shooting distance and position of the gun. 

PMID- 23857248
TI  - Preladenant, a selective adenosine A2A receptor antagonist, is not associated
      with QT/QTc prolongation.
AB  - PURPOSE: Preladenant is an orally administered adenosine2A (A2A) receptor
      antagonist in phase III development for Parkinson's disease treatment. This
      thorough QT/QTc study evaluated its potential effects on cardiac repolarization.
      METHODS: This was a randomized, double-blind, positive- and placebo-controlled,
      four-period crossover study performed under steady-state exposure of clinical and
      supratherapeutic doses of preladenant (10 mg BID and 100 mg BID, respectively,
      for 5 days), moxifloxacin (400 mg on day 5), or placebo in 60 healthy adult
      volunteers. The potential effect on QTcF was measured by the largest upper bound
      of 95 % one-sided CIs for the mean changes from time-matched baseline ECG
      recordings compared with placebo. Plasma preladenant concentrations were also
      determined on day 5. RESULTS: The QTcF difference for moxifloxacin compared with
      placebo exceeded 5 ms from 1 to 12 h postdose, establishing assay sensitivity.
      The QTcF interval was similar between the preladenant and placebo treatment
      groups: the upper bound of the 95 % one-sided CI for the mean difference in QTcF
      between preladenant and placebo was less than 10 ms at all time points for the
      supratherapeutic treatment group (1.3 to 5.7 ms, mean difference: -1.3 to 2.7 ms)
      and the therapeutic treatment group (0.4 to 4.3 ms, mean difference: -2.1 to 1.5
      ms), substantially below the threshold of regulatory concern. The
      supratherapeutic dose (100 mg BID) provided a Cmax margin of 6.1-fold and AUC
      margin of 6.9-fold, respectively, compared with 10 mg BID. CONCLUSIONS: At
      clinical and supratherapeutic doses, preladenant is not associated with QTc
      prolongation.

PMID- 23857249
TI  - Persistence to antihypertensive drug treatment in Swedish primary healthcare.
AB  - PURPOSE: To determine factors associated with low persistence in patients
      initiated on drug treatment for hypertension. METHODS: Cohort study using medical
      records for patients with hypertension in 48 Swedish primary healthcare centres.
      Data were linked to national registers on dispensed drugs, hospitalizations,
      outpatient hospital consultations, deaths, migration, and socioeconomy. We
      identified 5225 patients (55 % women, mean age 61 years) initiated on
      antihypertensive drug treatment during 2006-2007. Persistence was measured for
      two years by the dispensed drugs. Patients with a gap of >30 days between end of
      dispensed supply and the next dispensed prescription were classified as non
      persistent. This was calculated by Kaplan-Meier analysis. Cox proportional hazard
      regression was used to estimate hazard ratios for discontinuation. Potential
      predictors included age, gender, blood pressure before initiation of therapy,
      cardiovascular comorbidity, educational level, country of birth, and income.
      RESULTS: Among patients with a dispensed first prescription, 26 % discontinued
      treatment during the first year, and a further 9 % discontinued during the second
      year. Discontinuation (all adjusted) was more common in men (P = 0.002) and in
      younger patients (30-49 years, P < 0.001). Systolic (P < 0.001) but not diastolic
      blood pressure was positively associated with persistence. Native-born Swedish
      citizens and patients born in the other Nordic countries had lower
      discontinuation rates than those born outside the Nordic countries (P < 0.001).
      CONCLUSION: Major determinants of discontinuation of antihypertensive drug
      treatment are male sex, young age, mild-to-moderate systolic blood pressure
      elevation, and birth outside of Sweden.

PMID- 23857250
TI  - RAF kinase inhibitor-independent constitutive activation of Yes-associated
      protein 1 promotes tumor progression in thyroid cancer.
AB  - The transcription coactivator Yes-associated protein 1 (YAP1) is regulated by the
      Hippo tumor suppressor pathway. However, the role of YAP1 in thyroid cancer,
      which is frequently associated with the BRAF(V600E) mutation, remains unknown.
      This study aimed to investigate the role of YAP1 in thyroid cancer. YAP1 was
      overexpressed in papillary (PTC) and anaplastic thyroid cancer, and nuclear YAP1
      was more frequently detected in BRAF(V600E) (+) PTC. In the thyroid cancer cell
      lines TPC-1 and HTH7, which do not have the BRAF(V600E) mutation, YAP1 was
      cytosolic and inactive at high cell densities. In contrast, YAP1 was retained in
      the nucleus and its target genes were expressed in the thyroid cancer cells 8505C
      and K1, which harbor the BRAF(V600E) mutation, regardless of cell density.
      Furthermore, the nuclear activation of YAP1 in 8505C was not inhibited by RAF or
      MEK inhibitor. In vitro experiments, YAP1 silencing or overexpression affected
      migratory capacities of 8505C and TPC-1 cells. YAP1 knockdown resulted in marked
      decrease of tumor volume, invasion and distant metastasis in orthotopic tumor
      xenograft mouse models using the 8505C thyroid cancer cell line. Taken together,
      YAP1 is involved in the tumor progression of thyroid cancer and YAP1-mediated
      effects might not be affected by the currently used RAF kinase inhibitors. 

PMID- 23857251
TI  - Epigenetic silencing of monoallelically methylated miRNA loci in precancerous
      colorectal lesions.
AB  - Epigenetic silencing of protein-encoding genes is common in early-stage
      colorectal tumorigenesis. Less is known about the methylation-mediated silencing
      of genes encoding microRNAs (miRNAs), which are also important epigenetic
      modulators of gene expression. Using quantitative PCR, we identified 56 miRNAs
      that were expressed in normal colorectal mucosa and in HT29 colorectal cancer
      cells treated with demethylating agents but not in untreated HT29 cells,
      suggesting that they probably undergo methylation-induced silencing during
      colorectal tumorigenesis. One of these, miR-195, had recently been reported to be
      underexpressed in colorectal cancers and to exert tumor-suppressor effects in
      colorectal cancer cells. We identified the transcription start site (TSS) for
      primary miRNA (pri-miR)-497/195, the primary precursor that yields miR-195 and
      another candidate on our list, miR-497, and a single CpG island upstream to the
      TSS, which controls expression of both miRNAs. Combined bisulfite restriction
      analysis and bisulfite genomic sequencing studies revealed monoallelic
      methylation of this island in normal colorectal mucosa (50/50 samples) and full
      methylation in most colorectal adenomas (38/50; 76%). The hypermethylated
      precancerous lesions displayed significantly downregulated expression of both
      miRNAs. Similar methylation patterns were observed at two known imprinted genes,
      MEG3 and GNAS-AS1, which encode several of the 56 miRNAs on our list. Imprinting
      at these loci was lost in over half the adenomas (62% at MEG3 and 52% at GNAS
      AS1). Copy-number alterations at MEG3, GNAS-AS1 and pri-miR-497/195, which are
      frequent in colorectal cancers, were less common in adenomas and confined to
      tumors displaying differential methylation at the involved locus. Our data show
      that somatically acquired, epigenetic changes at monoallelically methylated
      regions encoding miRNAs are relatively frequent in sporadic colorectal adenomas
      and might contribute to the onset and progression of these tumors. 

PMID- 23857252
TI  - MicroRNA/gene profiling unveils early molecular changes and nuclear factor
      erythroid related factor 2 (NRF2) activation in a rat model recapitulating human
      hepatocellular carcinoma (HCC).
AB  - Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of
      hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions
      in humans. Experimental models recapitulating human hepatocellular carcinoma
      (HCC) are then used to perform this analysis. We performed miRNA and gene
      expression profiling to characterize the molecular events involved in the
      multistep process of hepatocarcinogenesis in the resistant-hepatocyte rat model.
      A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in
      early preneoplastic lesions positive for the stem/progenitor cell marker
      cytokeratin-19, indicating that several HCC-associated alterations occur from the
      very beginning of the carcinogenic process. Our analysis also identified
      miRNA/gene-target networks aberrantly activated at the initial stage of
      hepatocarcinogenesis. Activation of the nuclear factor erythroid related factor 2
      (NRF2) pathway and up-regulation of the miR-200 family were among the most
      prominent changes. The relevance of these alterations in the development of HCC
      was confirmed by the observation that NRF2 silencing impaired while miR-200a
      overexpression promoted HCC cell proliferation in vitro. Moreover, T3-induced in
      vivo inhibition of the NRF2 pathway accompanied the regression of cytokeratin-19
      positive nodules, suggesting that activation of this transcription factor
      contributes to the onset and progression of preneoplastic lesions towards
      malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat
      HCC have been previously associated with human HCC as well underlines the
      translational value of our results. CONCLUSION: This study indicates that most of
      the molecular changes found in HCC occur in the very early stages of
      hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may
      represent a new therapeutic target.

PMID- 23857253
TI  - Reactive oxygen species spermine metabolites generated from amine oxidases and
      radiation represent a therapeutic gain in cancer treatments.
AB  - The most frequent interventions in cancer therapy are currently the destruction
      of cells by irradiation or administration of drugs both able to induce radical
      formation and toxic metabolites by enzyme-catalyzed reactions. The aim of this
      study was to determine the cell viability of cells undergoing a DNA damage
      threshold accomplished by ROS overproduction via both ectopic expression of
      murine spermine oxidase (mSMOX) and bovine serum amine oxidase (BSAO) enzymes.
      Low dose of X-irradiation delivers a challenging dose of damage as evaluated in
      proficient Chinese hamster AA8 cell line and both deficient transcription-coupled
      nucleotide excision repair (NER) UV61 cells and deficient base excision repair
      (BER) EM9 cells, at 6 and 24 h after exposure. The priming dose of ROS
      overexposure by mSMOX provokes an adaptive response in N18TG2, AA8 and EM9 cell
      lines at 24 h. Interestingly, in the UV61 cells, ROS overexposure by mSMOX
      delivers an earlier adaptive response to radiation. The enzymatic formation of
      toxic metabolites has mainly been investigated on wild-type (WT) and multidrug
      resistant (MDR) cancer cell lines, using and spermine as substrate of the BSAO
      enzyme. MDR cells are more sensitive to the toxic polyamine metabolites than WT
      cells, thus indicating a new therapeutic strategy to overcome MDR tumors. Since
      SMOX in mammals is differentially activated in a tissue-specific manner and
      cancer cells can differ in terms of DNA repair and MDR capabilities, it could be
      of interest to simultaneously treat with very low dose of X-rays and/or to alter
      SMOX metabolism to generate a differential response in healthy and cancer
      tissues.

PMID- 23857254
TI  - A rare presentation of hypertrophic olivary degeneration secondary to primary
      central nervous system lymphoma.

PMID- 23857255
TI  - Self-organization of two-dimensional poly(3-hexylthiophene) crystals on Au(111)
      surfaces.
AB  - A novel approach to construct organized structures and tunable electronic
      properties of poly(3-hexylthiophene) (P3HT) monolayers on Au(111) surfaces was
      developed based on a self-assembly process in a liquid phase. On a bare Au(111)
      surface, P3HT adsorbs as a monolayer with a randomly oriented and curvy-wire
      morphology. When the gold surface was pre-modified by an iodine adlayer (I
      Au(111)), the passivation effect of iodine decreases the substrate-adsorbate
      interaction. As a result, P3HT adsorbs as linear chains, stacking and folding
      into regular arrays of a polymer bundle. By controlling the electrode at more
      negative potentials, it is able to desorb the iodine adlayer from the substrate.
      The remaining P3HT adsorbs onto the Au(111) surface directly, retaining a linear
      and regular arrangement. However, a different electronic structure is imaged by
      scanning tunneling microscopy (STM). The scanning tunneling spectroscopy (STS)
      analysis reveals that this molecular image is associated with a 0.16 eV shift of
      the Fermi level toward HOMO position, indicating a stronger p-doping
      characteristic of the adlayer. The phenomenon is ascribed to an iodine-induced p
      doping reaction which occurs during the desorption of iodine. This work
      demonstrates that electrode potential and pre-adsorbed halide adlayers can be
      effectively used to regulate the arrangement and electronic properties of
      adsorbed molecules on metallic substrates. 

PMID- 23857257
TI  - Experimental results of underwater cooperative source localization using a single
      acoustic vector sensor.
AB  - This paper aims at estimating the azimuth, range and depth of a cooperative
      broadband acoustic source with a single vector sensor in a multipath underwater
      environment, where the received signal is assumed to be a linear combination of
      echoes of the source emitted waveform. A vector sensor is a device that measures
      the scalar acoustic pressure field and the vectorial acoustic particle velocity
      field at a single location in space. The amplitudes of the echoes in the vector
      sensor components allow one to determine their azimuth and elevation. Assuming
      that the environmental conditions of the channel are known, source range and
      depth are obtained from the estimates of elevation and relative time delays of
      the different echoes using a ray-based backpropagation algorithm. The proposed
      method is tested using simulated data and is further applied to experimental data
      from the Makai'05 experiment, where 8-14 kHz chirp signals were acquired by a
      vector sensor array. It is shown that for short ranges, the position of the
      source is estimated in agreement with the geometry of the experiment. The method
      is low computational demanding, thus well-suited to be used in mobile and light
      platforms, where space and power requirements are limited. 

PMID- 23857258
TI  - Development of a network RTK positioning and gravity-surveying application with
      gravity correction using a smartphone.
AB  - This paper proposes a smartphone-based network real-time kinematic (RTK)
      positioning and gravity-surveying application (app) that allows semi-real-time
      measurements using the built-in Bluetooth features of the smartphone and a third
      generation or long-term evolution wireless device. The app was implemented on a
      single smartphone by integrating a global navigation satellite system (GNSS)
      controller, a laptop, and a field-note writing tool. The observation devices
      (i.e., a GNSS receiver and relative gravimeter) functioned independently of this
      system. The app included a gravity module, which converted the measured relative
      gravity reading into an absolute gravity value according to tides; meter height;
      instrument drift correction; and network adjustments. The semi-real-time features
      of this app allowed data to be shared easily with other researchers. Moreover,
      the proposed smartphone-based gravity-survey app was easily adaptable to various
      locations and rough terrain due to its compact size. 

PMID- 23857259
TI  - Background subtraction based on color and depth using active sensors.
AB  - Depth information has been used in computer vision for a wide variety of tasks.
      Since active range sensors are currently available at low cost, high-quality
      depth maps can be used as relevant input for many applications. Background
      subtraction and video segmentation algorithms can be improved by fusing depth and
      color inputs, which are complementary and allow one to solve many classic color
      segmentation issues. In this paper, we describe one fusion method to combine
      color and depth based on an advanced color-based algorithm. This technique has
      been evaluated by means of a complete dataset recorded with Microsoft Kinect,
      which enables comparison with the original method. The proposed method
      outperforms the others in almost every test, showing more robustness to
      illumination changes, shadows, reflections and camouflage. 

PMID- 23857260
TI  - Rice seed cultivar identification using near-infrared hyperspectral imaging and
      multivariate data analysis.
AB  - A near-infrared (NIR) hyperspectral imaging system was developed in this study.
      NIR hyperspectral imaging combined with multivariate data analysis was applied to
      identify rice seed cultivars. Spectral data was exacted from hyperspectral
      images. Along with Partial Least Squares Discriminant Analysis (PLS-DA), Soft
      Independent Modeling of Class Analogy (SIMCA), K-Nearest Neighbor Algorithm (KNN)
      and Support Vector Machine (SVM), a novel machine learning algorithm called
      Random Forest (RF) was applied in this study. Spectra from 1,039 nm to 1,612 nm
      were used as full spectra to build classification models. PLS-DA and KNN models
      obtained over 80% classification accuracy, and SIMCA, SVM and RF models obtained
      100% classification accuracy in both the calibration and prediction set. Twelve
      optimal wavelengths were selected by weighted regression coefficients of the PLS
      DA model. Based on optimal wavelengths, PLS-DA, KNN, SVM and RF models were
      built. All optimal wavelengths-based models (except PLS-DA) produced
      classification rates over 80%. The performances of full spectra-based models were
      better than optimal wavelengths-based models. The overall results indicated that
      hyperspectral imaging could be used for rice seed cultivar identification, and RF
      is an effective classification technique. 

PMID- 23857262
TI  - AmI and deployment considerations in AAL services provision for elderly
      independent living: the MonAMI project.
AB  - The MonAMI project aims to investigate the feasibility of the deployment of open
      platforms for Ambient Assisted Living (AAL) services provision based on Ambient
      Intelligence (AmI) and to test user acceptance and the usability of the services.
      Services were designed to provide support in the areas of environmental control,
      security, well-being and leisure. These services were installed and evaluated in
      a Spanish geriatric residence. The participants included elderly persons with
      disabilities, nursing home care givers and informal carers. The concept of the
      open platform proved to be satisfactory for the provision of the services in a
      context aware framework. Furthermore, the usability of the technology was viewed
      positively and the overall results indicate that this system has the potential to
      prolong independent living at home for elderly people with disabilities.
      Deployment was proven successful and awareness of open-platform AAL service
      delivery was raised in local communities throughout Europe. 

PMID- 23857261
TI  - Dental optical coherence tomography.
AB  - This review paper describes the applications of dental optical coherence
      tomography (OCT) in oral tissue images, caries, periodontal disease and oral
      cancer. The background of OCT, including basic theory, system setup, light
      sources, spatial resolution and system limitations, is provided. The comparisons
      between OCT and other clinical oral diagnostic methods are also discussed. 

PMID- 23857263
TI  - A radiosonde using a humidity sensor array with a platinum resistance heater and
      multi-sensor data fusion.
AB  - This paper describes the design and implementation of a radiosonde which can
      measure the meteorological temperature, humidity, pressure, and other atmospheric
      data. The system is composed of a CPU, microwave module, temperature sensor,
      pressure sensor and humidity sensor array. In order to effectively solve the
      humidity sensor condensation problem due to the low temperatures in the high
      altitude environment, a capacitive humidity sensor including four humidity
      sensors to collect meteorological humidity and a platinum resistance heater was
      developed using micro-electro-mechanical-system (MEMS) technology. A platinum
      resistance wire with 99.999% purity and 0.023 mm in diameter was used to obtain
      the meteorological temperature. A multi-sensor data fusion technique was applied
      to process the atmospheric data. Static and dynamic experimental results show
      that the designed humidity sensor with platinum resistance heater can effectively
      tackle the sensor condensation problem, shorten response times and enhance
      sensitivity. The humidity sensor array can improve measurement accuracy and
      obtain a reliable initial meteorological humidity data, while the multi-sensor
      data fusion technique eliminates the uncertainty in the measurement. The
      radiosonde can accurately reflect the meteorological changes. 

PMID- 23857264
TI  - Sensorized garments and textrode-enabled measurement instrumentation for
      ambulatory assessment of the autonomic nervous system response in the ATREC
      project.
AB  - Advances in textile materials, technology and miniaturization of electronics for
      measurement instrumentation has boosted the development of wearable measurement
      systems. In several projects sensorized garments and non-invasive instrumentation
      have been integrated to assess on emotional, cognitive responses as well as
      physical arousal and status of mental stress through the study of the autonomous
      nervous system. Assessing the mental state of workers under stressful conditions
      is critical to identify which workers are in the proper state of mind and which
      are not ready to undertake a mission, which might consequently risk their own
      life and the lives of others. The project Assessment in Real Time of the Stress
      in Combatants (ATREC) aims to enable real time assessment of mental stress of the
      Spanish Armed Forces during military activities using a wearable measurement
      system containing sensorized garments and textile-enabled non-invasive
      instrumentation. This work describes the multiparametric sensorized garments and
      measurement instrumentation implemented in the first phase of the project
      required to evaluate physiological indicators and recording candidates that can
      be useful for detection of mental stress. For such purpose different sensorized
      garments have been constructed: a textrode chest-strap system with six
      repositionable textrodes, a sensorized glove and an upper-arm strap. The
      implemented textile-enabled instrumentation contains one skin galvanometer, two
      temperature sensors for skin and environmental temperature and an impedance
      pneumographer containing a 1-channel ECG amplifier to record cardiogenic
      biopotentials. With such combinations of garments and non-invasive measurement
      devices, a multiparametric wearable measurement system has been implemented able
      to record the following physiological parameters: heart and respiration rate,
      skin galvanic response, environmental and peripheral temperature. To ensure the
      proper functioning of the implemented garments and devices the full series of 12
      sets have been functionally tested recording cardiogenic biopotential, thoracic
      impedance, galvanic skin response and temperature values. The experimental
      results indicate that the implemented wearable measurement systems operate
      according to the specifications and are ready to be used for mental stress
      experiments, which will be executed in the coming phases of the project with
      dozens of healthy volunteers. 

PMID- 23857265
TI  - Vapor trace recognition using a single nonspecific chemiresistor.
AB  - An application of spectral analysis to the transient response signals of ALD
      fabricated conductometric sensors (chemiresistors) upon exposure to short vapor
      pulses is discussed. It is based on the representation of a response curve in the
      frequency domain, followed by the multi-dimensional Quadratic Discriminant
      Analysis (QDA) for analyte identification. Compared to the standard steady-state
      amplitude analysis, this technique does not depend on a short-term sensor drift,
      does not have limitations for the number of extracted features and has a strict
      physical validation. Effective recognition of some relatively simple combustible
      analytes (acetone, toluene, ethanol) was demonstrated using a single nonspecific
      chemiresistor. 

PMID- 23857267
TI  - Seamless positioning and navigation by using geo-referenced images and multi
      sensor data.
AB  - Ubiquitous positioning is considered to be a highly demanding application for
      today's Location-Based Services (LBS). While satellite-based navigation has
      achieved great advances in the past few decades, positioning and navigation in
      indoor scenarios and deep urban areas has remained a challenging topic of
      substantial research interest. Various strategies have been adopted to fill this
      gap, within which vision-based methods have attracted growing attention due to
      the widespread use of cameras on mobile devices. However, current vision-based
      methods using image processing have yet to revealed their full potential for
      navigation applications and are insufficient in many aspects. Therefore in this
      paper, we present a hybrid image-based positioning system that is intended to
      provide seamless position solution in six degrees of freedom (6DoF) for location
      based services in both outdoor and indoor environments. It mainly uses visual
      sensor input to match with geo-referenced images for image-based positioning
      resolution, and also takes advantage of multiple onboard sensors, including the
      built-in GPS receiver and digital compass to assist visual methods. Experiments
      demonstrate that such a system can greatly improve the position accuracy for
      areas where the GPS signal is negatively affected (such as in urban canyons), and
      it also provides excellent position accuracy for indoor environments. 

PMID- 23857266
TI  - Microarray dot electrodes utilizing dielectrophoresis for cell characterization.
AB  - During the last three decades; dielectrophoresis (DEP) has become a vital tool
      for cell manipulation and characterization due to its non-invasiveness. It is
      very useful in the trend towards point-of-care systems. Currently, most efforts
      are focused on using DEP in biomedical applications, such as the spatial
      manipulation of cells, the selective separation or enrichment of target cells,
      high-throughput molecular screening, biosensors and immunoassays. A significant
      amount of research on DEP has produced a wide range of microelectrode
      configurations. In this paper; we describe the microarray dot electrode, a
      promising electrode geometry to characterize and manipulate cells via DEP. The
      advantages offered by this type of microelectrode are also reviewed. The protocol
      for fabricating planar microelectrodes using photolithography is documented to
      demonstrate the fast and cost-effective fabrication process. Additionally;
      different state-of-the-art Lab-on-a-Chip (LOC) devices that have been proposed
      for DEP applications in the literature are reviewed. We also present our recently
      designed LOC device, which uses an improved microarray dot electrode
      configuration to address the challenges facing other devices. This type of LOC
      system has the capability to boost the implementation of DEP technology in
      practical settings such as clinical cell sorting, infection diagnosis, and
      enrichment of particle populations for drug development. 

PMID- 23857269
TI  - Letter from the editor.

PMID- 23857270
TI  - Approaches to the vaccination of pregnant women: experience from Stockport, UK,
      with prenatal influenza.
AB  - For the 2010/11 influenza season the prenatal vaccination program was extended to
      all women in England and Wales irrespective of gestational age--this was a
      considerable shift in practice for both pregnant women and healthcare providers
      where the emphasis previously had been only on targeted vaccination for pregnant
      women with adverse risk factors for influenza infection. This paper will describe
      the program's operation in Stockport, UK during this season when uptake was among
      the highest in the England and Wales. Stockport is situated in the south east of
      Greater Manchester. It is a generally affluent area with a population of 295,000.
      Health indicators are generally higher than the regional average. The target
      population for influenza is just under 50,000 residents (excluding pregnant
      women).

PMID- 23857271
TI  - NIC23.
AB  - The 23rd National Immunization Conference for Health Care Workers was held on
      December 7th, 2012 at the Manchester Conference Centre. There were over 220
      delegates for this event sponsored by educational grants from Crucell, Glaxo
      Smith Kline, Pfizer Vaccines and Sanofi Pasteur. A number of speakers took the
      opportunity kindly afforded by Human Vaccines and Immunotherapeutics to write up
      their conference presentation as a paper for this special supplement. 

PMID- 23857272
TI  - Preclinical evaluation of Vaxfectin-adjuvanted Vero cell-derived seasonal split
      and pandemic whole virus influenza vaccines.
AB  - Increasing the potency and supply of seasonal and pandemic influenza vaccines
      remains an important unmet medical need which may be effectively accomplished
      with adjuvanted egg- or cell culture-derived vaccines. Vaxfectin, a cationic
      lipid-based adjuvant with a favorable safety profile in phase 1 plasmid DNA
      vaccines trials, was tested in combination with seasonal split, trivalent and
      pandemic whole virus, monovalent influenza vaccines produced in Vero cell
      cultures. Comparison of hemagglutination inhibition (HI) antibody titers in
      Vaxfectin-adjuvanted to nonadjuvanted vaccinated mice and guinea pigs revealed 3-
      to 20-fold increases in antibody titers against each of the trivalent influenza
      virus vaccine strains and 2- to 8-fold increases in antibody titers against the
      monovalent H5N1 influenza virus vaccine strain. With the vaccine doses tested,
      comparable antibody responses were induced with formulations that were freshly
      prepared or refrigerated at conventional 2-8 degrees C storage conditions for up
      to 6 mo. Comparison of T-cell frequencies measured by interferon-gamma ELISPOT
      assay between groups revealed increases of between 2- to 10-fold for each of the
      adjuvanted trivalent strains and up to 22-fold higher with monovalent H5N1
      strain. Both trivalent and monovalent vaccines were easy to formulate with
      Vaxfectin by simple mixing. These preclinical data support further testing of
      Vaxfectin-adjuvanted Vero cell culture vaccines toward clinical studies designed
      to assess safety and immunogenicity of these vaccines in humans.

PMID- 23857273
TI  - Persistence clinical studies: can you believe what you see?
AB  - Long-term immunity, evaluated by the persistence of antibody titers, is important
      to assess duration of protection induced by vaccination. This paper aims at
      drawing awareness on the risk of misinterpreting persistence results in absence
      of adjustment for missing or left-censored data. Using simulations, the paper
      shows that repeated measurement models are an appropriate alternative to control
      the bias associated to unadjusted persistence results. 

PMID- 23857276
TI  - Crystal structure of the yeast TSC1 core domain and implications for tuberous
      sclerosis pathological mutations.
AB  - Tuberous sclerosis complex is a disease caused by mutations in two tumor
      suppressor genes, TSC1 and TSC2. The TSC1 protein, also known as hamartin, has a
      critical role in controlling mTOR signalling. TSC1 does not bear apparent
      sequence homology with other proteins. Here we show that the N-terminal half of
      yeast TSC1 forms a protease-resistant domain, which is evolutionarily conserved.
      The crystal structure of this yeast TSC1 core domain shows that it contains a
      pseudo-HEAT repeat fold with its C-terminal end capped by a helical subdomain.
      This allows us to model the three-dimensional structure of the human TSC1 N
      terminal domain (TSC1-NTD), which anchors essentially all pathogenic TSC1
      missense mutations found in tuberous sclerosis patients. Interestingly, most
      pathogenic mutations map inside of the folded TSC1-NTD structure, whereas most
      non-pathogenic variants are on the structural surface. This indicates that the
      disruption of the TSC1-NTD globular structure is a major cause of tuberous
      sclerosis. 

PMID- 23857278
TI  - Drug abuse: another challenge for the cardiologist?
AB  - The abuse of illicit drugs is a major social and health problem. In fact, illicit
      drugs are responsible for many adverse systemic effects, which may require urgent
      medical treatment. In the present review, we report details on the prevalence of
      the major illicit drugs abused in Europe in 2009, according to the 2011 report of
      the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), focusing on
      the effects on the cardiovascular system, including sudden cardiac death. 

PMID- 23857277
TI  - The human impact of tsunamis: a historical review of events 1900-2009 and
      systematic literature review.
AB  - Introduction. Although rare, tsunamis have the potential to cause considerable
      loss of life and injury as well as widespread damage to the natural and built
      environments. The objectives of this review were to describe the impact of
      tsunamis on human populations in terms of mortality, injury, and displacement
      and, to the extent possible, identify risk factors associated with these
      outcomes. This is one of five reviews on the human impact of natural disasters.
      Methods. Data on the impact of tsunamis were compiled using two methods, a
      historical review from 1900 to mid 2009 of tsunami events from multiple databases
      and a systematic literature review to October 2012 of publications. Analysis
      included descriptive statistics and bivariate tests for associations between
      tsunami mortality and characteristics using STATA 11. Findings. There were
      255,195 deaths (range 252,619-275,784) and 48,462 injuries (range 45,466-51,457)
      as a result of tsunamis from 1900 to 2009. The majority of deaths (89%) and
      injuries reported during this time period were attributed to a single event -the
      2004 Indian Ocean tsunami. Findings from the systematic literature review
      indicate that the primary cause of tsunami-related mortality is drowning, and
      that females, children and the elderly are at increased mortality risk. The few
      studies that reported on tsunami-related injury suggest that males and young
      adults are at increased injury-risk. Conclusions. Early warning systems may help
      mitigate tsunami-related loss of life. 

PMID- 23857274
TI  - Vaccines against meningococcal serogroup B disease containing outer membrane
      vesicles (OMV): lessons from past programs and implications for the future.
AB  - The utility of wild-type outer membrane vesicle (wtOMV) vaccines against
      serogroup B (MenB) meningococcal disease has been explored since the 1970s.
      Public health interventions in Cuba, Norway and New Zealand have demonstrated
      that these protein-based vaccines can prevent MenB disease. Data from large
      clinical studies and retrospective statistical analyses in New Zealand give
      effectiveness estimates of at least 70%. A consistent pattern of moderately
      reactogenic and safe vaccines has been seen with the use of approximately 60
      million doses of three different wtOMV vaccine formulations. The key limitation
      of conventional wtOMV vaccines is their lack of broad protective activity against
      the large diversity of MenB strains circulating globally. The public health
      intervention in New Zealand (between 2004-2008) when MeNZB was used to control a
      clonal MenB epidemic, provided a number of new insights regarding international
      and public-private collaboration, vaccine safety surveillance, vaccine
      effectiveness estimates and communication to the public. The experience with
      wtOMV vaccines also provide important information for the next generation of MenB
      vaccines designed to give more comprehensive protection against multiple strains.

PMID- 23857279
TI  - Dolicho-right coronary artery emptying in coronary sinus: a rare, 'snake-like',
      giant coronary fistula.

PMID- 23857280
TI  - Rodent animal models of delayed bone healing and non-union formation: a
      comprehensive review.
AB  - Despite the growing knowledge on the mechanisms of fracture healing, delayed
      healing and non-union formation remain a major clinical challenge. Animal models
      are needed to study the complex process of normal and impaired fracture healing
      and to develop new therapeutic strategies. Whereas in the past mainly large
      animals have been used to study normal and impaired fracture healing, nowadays
      rodent models are of increasing interest. New osteosynthesis techniques for rat
      and mice have been developed during the last years, which allowed for the first
      time stable osteosynthesis in these animals comparable to the standards in large
      animals and humans. Based on these new implants, different models in rat and mice
      have been established to study delayed healing and non-union formation. Although
      in humans the terms delayed union and non-union are well defined, in rodents
      definitions are lacking. However, especially in scientific studies clear
      definitions are necessary to develop a uniform scientific language and allow
      comparison of the results between different studies. In this consensus report, we
      define the basic terms "union", "delayed healing" and "non-union" in rodent
      animal models. Based on a review of the literature and our own experience, we
      further provide an overview on available models of delayed healing and non-union
      formation in rats and mice. We further summarise the value of different
      approaches to study normal and delayed fracture healing as well as non-union
      formation, and discuss different methods of data evaluation. 

PMID- 23857281
TI  - Association between X-ray repair cross-complementing group 1 Arg194Trp
      polymorphism and colorectal cancer risk.
AB  - The polymorphism of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, a
      substitution of Arg to Gln at position 194, has been implicated in the
      development of colorectal cancer (CRC) in a number of case-control studies with
      contradictory and inconclusive findings. The current meta-analysis of all
      currently available publications was conducted to assess the gene susceptibility
      to CRC and improve our understanding of the CRC pathogenesis. The pooled odds
      ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated
      by use of fixed-effects model or random-effects model when appropriate. A total
      of 15 eligible case-control studies with 4,501 cases and 8,038 controls were
      retrieved after a comprehensive search of the PubMed, Embase, Web of science, and
      Chinese Biomedicine (CBM) databases up to December 2012. The overall meta
      analysis identified a positive but not statistically significant association
      between the XRCC1 Arg194Trp polymorphism and CRC risk under all genetic contrast
      models (ORTrp vs. Arg = 1.07, 95 % CI 0.90-1.26, P OR = 0.441; ORTrpTrp vs.
      ArgArg = 1.28, 95 % CI 0.91-1.81, P OR = 0.163; ORArgTrp vs. ArgArg = 1.00, 95 %
      CI 0.85-1.19, P OR = 0.956; ORArgTrp + TrpTrp vs. ArgArg = 1.06, 95 % CI 0.90
      1.24, P OR = 0.502; ORTrpTrp vs. ArgArg + ArgTrp = 1.11, 95 % CI 0.91-1.34, P OR
      = 0.306). The genotype TrpTrp carriers among Caucasians were more susceptible to
      CRC, although lack statistical evidence (ORTrpTrp vs. ArgArg = 2.69, 95 % CI 0.97
      7.49, P OR = 0.058; ORTrpTrp vs. ArgArg + ArgTrp = 2.77, 95 % CI 0.99-7.72, P OR
      = 0.051). Interestingly, the XRCC1 Arg194Trp variant was significantly associated
      with an increased risk of colon cancer. The present meta-analysis suggests that
      the XRCC1 Arg194Trp polymorphism may modify the risk for CRC, particularly colon
      cancer. However, the precise genetic association needs to be further estimated in
      future studies.

PMID- 23857282
TI  - Clinicopathological significance of hypoxia-inducible factor-1 alpha
      polymorphisms in cancers: evidence from a meta-analysis.
AB  - The associations between hypoxia-inducible factor-1 alpha (HIF-1alpha) and
      clinicopathological characteristics of cancers have been evaluated in various
      studies, with the conflicting results. Therefore, we conducted a meta-analysis by
      combining available data to derive a more precise estimation of the association.
      PubMed, Embase, and China National Knowledge Infrastructure (CNKI) were searched
      until February 2013 to identify eligible studies. A total of 25 studies were
      included, with all studies investigating the role of HIF-1alpha C1772T
      polymorphism in clinicopathological parameters in cancers while 17 of them
      investigating HIF-1alpha G1790A polymorphism only. Results suggested that HIF
      1alpha C1772T polymorphism was associated with histological grade of cancer (T/T
      + C/T vs. C/C, grade 3 vs. grade 2: OR = 1.51, 95% CI = 1.08-2.13; grade 2 vs.
      grade 1: OR = 0.67, 95% CI = 0.46-0.97) and increased risk of lymph node
      metastasis (T/T + C/T vs. C/C: OR = 1.38, 95% CI = 1.13-1.68). HIF-1alpha G1790A
      polymorphism was found to be associated with increased risk of larger tumor size
      (G/G + G/A vs. A/A: OR = 1.64, 95% CI = 1.04-2.58) and borderline significant
      risk of lymph node metastasis (G/G + G/A vs. A/A: OR = 1.33, 95% CI = 1.00-1.78).
      Therefore, HIF-1alpha polymorphisms could be a potential prognostic factor for
      cancer. Further studies with larger data set and well-designed models are
      required to validate our findings.

PMID- 23857283
TI  - Prognostic significance of nemo-like kinase (NLK) expression in patients with
      gallbladder cancer.
AB  - Nemo-like kinase (NLK), a serine/threonine protein kinase, has been implicated in
      tumor development and progression, and plays an important role in diverse
      signaling pathways by phosphorylating a variety of transcription factors. Recent
      studies demonstrated that altered expression of NLK was observed in various types
      of human cancers. However, the clinical significance of NLK expression in
      gallbladder cancer (GBC) remains largely unknown. In this study, we focused on
      the clinical significance of NLK in GBC, and found that nuclear NLK protein
      overexpression was frequently detected in GBC tissues. The overexpression of NLK
      was significantly correlated with histological grade, TNM stage, and perineural
      invasion. The results of Kaplan-Meier analysis indicated that a high expression
      level of NLK resulted in a significantly poorer prognosis of GBC patients (P =
      0.002). Furthermore, multivariate Cox regression analysis showed that high NLK
      expression was an independent prognostic factor for GBC patients (HR = 3.077). In
      conclusion, overexpression of NLK is closely related to progression of GBC, and
      NLK could be used as a potential prognostic marker for GBC patients.

PMID- 23857284
TI  - Expression and significance of miRNA-21 and BTG2 in lung cancer.
AB  - This study investigates the expression of micro-ribonucleic acid-21 (miRNA-21)
      and B cell translocation gene 2 (BTG2) in lung cancer cells. We examined the
      impact of miRNA-21 on biological characteristics of lung cancer cells, such as
      growth, proliferation, apoptosis, and invasion. The expression of miRNA-21 and
      BTG2 protein in lung cancer cell lines (A549, HCC827, NCI-H292, and 95-D) was
      examined using quantitative reverse transcription-polymerase chain reaction and
      Western blot analysis, respectively. Subsequently, the regulatory role of miRNA
      21 on BTG2 was explored by inhibiting miRNA-21 expression in 95-D cells using
      miRNA-21-antisense oligonucleotides (miRNA-21 ASO). The impact of miRNA-21 on the
      biological characteristics of 95-D cells was further studied using methylthiazol
      tetrazolium assays, flow cytometry, and Transwell invasion chamber assays. The
      impact of miRNA-21 on the expression of cyclin D1, caspase-3, and matrix
      metalloprotease-9 (MMP9) was also studied. miRNA-21 expression was significantly
      higher in lung cancer cell lines (A549, HCC827, NCI-H282, and 95-D) than that in
      normal human bronchial epithelial cells (HBE; p < 0.05). The pattern of BTG2
      protein expression was exactly the opposite of miRNA-21 expression in lung cancer
      cells. BTG2 was highly expressed in HBE cells and was expressed at very low
      levels in lung cancer cell lines (A549, HCC827, NCI-H292, and 95-D). High miRNA
      21 expression may inhibit BTG2 protein expression, whereas the inhibition of
      miRNA-21 expression may promote BTG2 protein expression in 95-D cells. Cell
      viability and invasion of 95-D cells were significantly lower in the miRNA-21 ASO
      transfected group than that in the control ASO-transfected group and
      untransfected group (p < 0.05). The number of apoptotic cells was significantly
      higher in the miRNA-21 ASO-transfected group than that in the control ASO
      transfected and untransfected groups (p < 0.05). The expression level of cyclin
      D1 and MMP9 in 95-D cells was significantly lower in the miRNA-21 ASO-transfected
      group than in the control ASO-transfected and untransfected groups (p < 0.05).
      Meanwhile, caspase-3 expression was significantly higher in the miRNA-21 ASO
      transfected group than that in the control ASO-transfected and untransfected
      groups (p < 0.05). miRNA-21 overexpression may inhibit the BTG2 gene in lung
      cancer cells. miRNA-21 may promote cell proliferation and invasion and inhibit
      cell apoptosis in 95-D cells.

PMID- 23857285
TI  - Prognostic significance of cyclooxygenase-2 in osteosarcoma: a meta-analysis.
AB  - Published studies researching the prognostic significance of cyclooxygenase-2
      (COX-2) expression in patients with osteosarcoma are inconclusive and
      heterogeneous. We conducted a meta-analysis to assess its prognostic value more
      precisely. The pooled odds ratios (ORs) or hazard ratios (HRs) with corresponding
      95 % confidence intervals (CIs) were calculated to evaluate the effects. Fourteen
      studies with 735 osteosarcoma patients were included to estimate the relationship
      between COX-2 and metastasis of tumor, clinical stage, and 3-year overall
      survival. High expressions of COX-2 predicted neoplasm metastasis (OR = 1.891, 95
      % CI 1.276-2.803, P = 0.002), advanced clinical stage (OR = 1.801, 95 % CI 1.257
      2.581, P = 0.001). In addition, high COX-2 expression tended to be associated
      with a poor 3-year survival (HR = 1.741, 95 % CI 0.762-3.979, P = 0.188), but the
      difference was not significant. Therefore, this meta-analysis demonstrated that
      high COX-2 expression might be an unfavorable prognostic effect in osteosarcoma.

PMID- 23857288
TI  - The healing effect of shark cartilage in rabbits after colonic anastomosis.
AB  - AIM: Shark cartilage has anti-inflammatory, analgesic, anti-angiogenic, anti
      tumoral, and immunomodulatory properties. We studied the effect of shark
      cartilage on the healing of colonic anastomoses, which are among the
      gastrointestinal system anastomoses that most commonly cause leakage. MATERIAL OF
      STUDY: Rabbits were divided into two groups of seven as the study and control
      groups. A normal diet was given to both groups before and after right colonic
      anastomosis. Shark cartilage tablets were given orally to the study group for
      five days before and after the anastomosis. Bursting pressures, hydroxyproline
      levels and translocation of the intestinal flora in anastomosis region were
      evaluated on the 6th day by operating on both groups. RESULTS: Bursting pressure
      and hydroxproline levels were higher in the experimental group compared to the
      control group (p<0.05). An increase in connective tissue and vascularization
      without growth of microorganisms was observed in the experimental group on
      microbiological examination. CONCLUSIONS: Shark cartilage given orally to rabbits
      increased anastomotic healing and did not cause serious consequences such as
      bacterial translocation.

PMID- 23857286
TI  - Polyunsaturated fatty acids and their relation with bone and muscle health in
      adults.
AB  - Age-related bone and muscle loss are major public health problems.
      Investigational therapies to reduce these losses include anti-inflammatory
      dietary supplementations, such as polyunsaturated fatty acids (PUFA).
      Surprisingly, this topic has received little attention in the osteoporosis
      community. Recent research highlights the role of PUFA in inflammatory regulation
      of bone remodeling via cellular pathways. Emerging research suggests significant
      roles for PUFA in reducing bone and muscle loss with aging; however, findings are
      conflicted for PUFA and fracture risk. Limited studies suggest a relation between
      higher omega-3 FA and better muscle/bone in older adults. This review highlights
      new research since 2008 and synthesizes our current understanding of PUFA in
      relation to bone and muscle. Across study designs, evidence indicates that PUFA
      has positive effects upon bone. As data are sparse, future clinical trials and
      prospective studies are important to determine the long term benefits of PUFA
      supplementation upon bone and muscle outcomes. 

PMID- 23857287
TI  - Interleukin-6 limits influenza-induced inflammation and protects against fatal
      lung pathology.
AB  - Balancing the generation of immune responses capable of controlling virus
      replication with those causing immunopathology is critical for the survival of
      the host and resolution of influenza-induced inflammation. Based on the capacity
      of interleukin-6 (IL-6) to govern both optimal T-cell responses and inflammatory
      resolution, we hypothesised that IL-6 plays an important role in maintaining this
      balance. Comparison of innate and adaptive immune responses in influenza-infected
      wild-type control and IL-6-deficient mice revealed striking differences in virus
      clearance, lung immunopathology and generation of heterosubtypic immunity. Mice
      lacking IL-6 displayed a profound defect in their ability to mount an anti-viral
      T-cell response. Failure to adequately control virus was further associated with
      an enhanced infiltration of inflammatory monocytes into the lung and an elevated
      production of the pro-inflammatory cytokines, IFN-alpha and TNF-alpha. These
      events were associated with severe lung damage, characterised by profound
      vascular leakage and death. Our data highlight an essential role for IL-6 in
      orchestrating anti-viral immunity through an ability to limit inflammation,
      promote protective adaptive immune responses and prevent fatal immunopathology. 

PMID- 23857289
TI  - Obituary: Professor Gerald Elliott.

PMID- 23857290
TI  - Mechanism and controlled growth of shape and size variant core/shell FeO/Fe3O4
      nanoparticles.
AB  - We report a novel synthesis approach for the growth of core/shell FeO/Fe3O4
      nanoparticles with controlled shape and size. FeO particles were partially
      oxidized to form core/shell FeO/Fe3O4 structures, as evidenced from transmission
      electron microscopy, X-ray diffraction, and magnetometry analysis. We find that
      the molar ratios and concentrations of surfactants are the key parameters in
      controlling the particle size. The particles can grow in either isotropic or
      anisotropic shapes, depending upon a chemical reaction scheme that is controlled
      kinetically or thermodynamically. The competitive growth rates of {111} and {100}
      facets can be used to tune the final shape of nanoparticles to spherical, cubic,
      octahedral, octopod, and cuboctahedral geometries. FeO particles can also be
      oxidized chemically or thermally to form Fe3O4 nanoparticles. By following the
      same synthesis technique, it is possible to synthesize rods and triangles of
      Fe3O4 by introducing twinnings and defects into the crystal structure of the
      seed. The thermally activated first-order Verwey transition at ~120 K has been
      observed in all the synthesized FeO/Fe3O4 nanoparticles, indicating its
      independence from the particle shape. These core/shell nanoparticles exhibit a
      strong shift in field-cooled hysteresis loops accompanied by an increase in
      coercivity (the so-called exchange bias effect), but the low field-switching
      behavior appears to vary with the particle shape.

PMID- 23857291
TI  - On-line capillary electrophoresis derivatization method for high sensitivity
      analysis of ubiquitin in filtered cerebrospinal fluid.
AB  - Electrophoretically mediated microanalysis was implemented for on-line
      fluorescence derivatization of ubiquitin (UBI), a potential biomarker of
      Alzheimer disease. Ubiquitin was labeled on its amino groups by the Fluoprobes(r)
      488 N-hydroxysuccinimide. The pH of the BGE, the applied electric field, and the
      washing process of the capillary were optimized. The best derivatization yield
      was obtained at pH 9.5 under an electric field of ~210 V/cm. The concentration
      and volume of the fluorescent dye as well as the sample medium and volume of
      injected UBI were also optimized. In order to improve further the LOD of UBI,
      electrophoretically mediated microanalysis was performed in a wider (100 MUm id)
      and longer (110 cm) capillary. As expected, these capillary dimensions improved
      the analytical sensitivity of UBI when compared to the 50 MUm id capillary. Under
      the optimized conditions, this analytical methodology allowed the analysis of
      free UBI in standard solution with a LOD of ~15 nM. Finally, the on-line
      fluorescent derivatization of UBI was applied to the detection and the
      quantification of UBI in cerebrospinal fluid (CSF) samples. Due to the high salt
      concentration of biological samples, desalting of CSF was required prior to the
      CE analysis. Quantification of UBI in CSF either by a direct evaluation of peak
      areas or using the standard addition method was achieved. 

PMID- 23857293
TI  - Quantitative positron emission tomography imaging of angiogenesis in rats with
      forelimb ischemia using (68)Ga-NOTA-c(RGDyK).
AB  - Gallium-68-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-cyclic Arg
      Gly-Asp-D-Tyr-Lys (c(RGDyK)) was developed for alphavbeta3 targeting, and is a
      promising agent for imaging of cancer and disorders related to angiogenesis. In
      this study, we performed kinetic analysis of (68)Ga-NOTA-c(RGDyK) in rats with
      surgically induced forelimb ischemia, and immunohistochemical analysis was also
      performed to assess alphavbeta3 immuno-staining level. Animal models were created
      by excision of the left brachial vessels, and a sham operation was performed on
      the right brachial region under 2 % isoflurane anesthesia. Using an animal
      positron emission tomography/computed tomography (PET/CT) scanner, a list mode
      PET scan (120 min) was started with the injection of (68)Ga-NOTA-c(RGDyK) via the
      tail vein at 3, 5 and 7 days after ischemic surgery. Volumes of interest were
      drawn on the left ventricle, sham operation, control, and ischemic regions.
      Compartmental and two graphical analyses (Logan and RE plots) were performed for
      kinetic parameter estimation. The immunohistochemical analysis was also performed
      after the last PET scan, and cell components were scored on a six point scale for
      quantification of immuno-staining level (0-negative to 5-very high). A 3
      compartment model with reversible binding best described the tissue time-activity
      curves. The distribution volume of the ischemic region was significantly higher
      than that of the sham operation (P < 10(-6)) and control region (P < 10(-9)).
      Both the Logan and RE plots showed high correlation with compartmental analysis
      (R(2) = 0.96 and 0.95 for Logan and RE, respectively). The temporal changes in
      distribution volume and binding potential were not significant. The immuno
      staining level of the ischemic region was significantly higher than that of sham
      operation (P < 10(-4)) and control region (P < 10(-8)). Kinetic modeling studies
      with dynamic (68)Ga-NOTA-c(RGDyK) PET scan are feasible based on an image-derived
      input function in a rat ischemia model. The kinetic modeling analysis performed
      in this study will be useful for the quantitative evaluation of (68)Ga-NOTA
      c(RGDyK) binding to alphavbeta3 in angiogenic tissues.

PMID- 23857294
TI  - Reduced frequency of CD56 dim CD16 pos natural killer cells in pediatric systemic
      inflammatory response syndrome/sepsis patients.
AB  - BACKGROUND: Sepsis continues to be a leading cause of death in infants and
      children. Natural killer (NK) cells serve as a bridge between innate and adaptive
      immunity, yet their role in pediatric sepsis has not been well characterized.
      METHODS: We tested the hypothesis that decreased NK cell cytotoxicity is a common
      feature of pediatric systemic inflammatory response syndrome (SIRS)/sepsis
      patients by measuring, using flow cytometry, NK cell cytotoxicity and cell
      surface phenotype in the peripheral blood of 38 pediatric intensive care patients
      who demonstrated signs and symptoms of SIRS and/or sepsis. RESULTS: NK cell
      cytotoxicity was significantly reduced in peripheral blood mononuclear cells
      (PBMCs) of pediatric SIRS/sepsis patients as compared with healthy controls, and
      the percentage of CD56(dim) CD16(+) cytotoxic NK cells in PBMCs was lower in
      patients with SIRS/sepsis than in normal donors. However, on a per cell basis,
      CD56(dim) CD16(+) NK cells in patients mediated cytotoxicity as well as those in
      normal donors. CONCLUSION: The NK cell dysfunction in pediatric SIRS/sepsis
      patients reflects a quantitative rather than a qualitative difference from
      healthy controls.

PMID- 23857295
TI  - Identifying term breast-fed infants at risk of significant hyperbilirubinemia.
AB  - BACKGROUND: The aim of this study was to establish a model to identify term
      breast-fed infants who are at risk of developing significant neonatal
      hyperbilirubinemia. METHODS: A prospective study was designed to investigate the
      effects of birth weight, mode of delivery, cephalohematoma, glucose-6-phosphate
      dehydrogenase (G6PD) deficiency, predischarge total serum bilirubin, variant
      uridine 5'diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene, and hepatic solute
      carrier organic anion transporter 1B1 (SLCO1B1) gene on significant
      hyperbilirubinemia in term breast-fed neonates. Significant hyperbilirubinemia
      was defined as a bilirubin level exceeding the hour-specific phototherapy
      treatment threshold recommended by the American Academy of Pediatrics in 2004.
      RESULTS: Of 240 exclusively breast-fed term neonates, 26 (10.8%) had significant
      hyperbilirubinemia. The predischarge total serum bilirubin on the third day (odds
      ratio (OR) = 2.63; 95% confidence interval (CI): 1.87-3.70; P < 0.001) and the
      variant UGT1A1 gene at nucleotide 211 (OR = 5.00; 95% CI: 1.08-23.03; P < 0.05)
      were significant risk factors. The area under the receiver operating
      characteristic (ROC) curve of the predictive probability was 0.964 (95% CI: 0.932
      0.984; P < 0.0001). CONCLUSION: Combining the total serum bilirubin on the third
      day and the variant UGT1A1 gene at nucleotide 211 can predict hyperbilirubinemia
      well in term breast-fed infants.

PMID- 23857296
TI  - Clinical exercise interventions in pediatric oncology: a systematic review.
AB  - Studies in pediatric oncology have shown a positive effect of physical activity
      on disease- and treatment-related side effects. Although several reviews have
      approved the benefits of therapeutic exercise for adult cancer patients, no
      systematic review exists summarizing the evidence of physical activity in
      pediatric oncology. We identified a total of 17 studies using the PubMed database
      and Cochrane library. To evaluate the evidence, we used the evaluation system of
      the Oxford Center for Evidence-Based Medicine 2001. The findings confirm that
      clinical exercise interventions are feasible and safe, especially with acute
      lymphoblastic leukemia (ALL) patients and during medical treatment. No adverse
      effects have been reported. Positive effects were found on fatigue, strength, and
      quality of life. Single studies present positive effects on the immune system,
      body composition, sleep, activity levels, and various aspects of physical
      functioning. Child-specific aspects such as cognitive abilities, growth,
      adolescence, and reintegration into peer-groups, school, and sports have barely
      been taken into consideration. The evidence for exercise interventions in
      pediatric oncology is rated level "3." Although the results are very promising,
      future research of high methodological quality and focusing on child-specific
      aspects is needed to establish evidence-based exercise recommendations,
      particularly for childhood cancer patients. 

PMID- 23857297
TI  - Fetal and infant growth predict hip geometry at 6 y old: findings from the
      Southampton Women's Survey.
AB  - BACKGROUND: We investigated relationships between early growth and proximal
      femoral geometry at age 6 y in a prospective population-based cohort, the
      Southampton Women's Survey. METHODS: In 493 mother-offspring pairs, we assessed
      linear size using high-resolution ultrasound at 11, 19, and 34 wk gestation
      (femur length) and at birth and 1, 2, 3, 4, and 6 y (crown-heel length/height).
      SD scores were created and conditional regression modeling generated mutually
      independent growth variables. Children underwent hip dual-energy X-ray
      absorptiometry (DXA) at 6 y; hip structure analysis software yielded measures of
      geometry and strength. RESULTS: There were strong associations between early
      linear growth and femoral neck section modulus (Z) at 6 y, with the strongest
      relationships observed for femur growth from 19 to 34 wk gestation (beta = 0.26
      cm(3)/SD, P < 0.0001), and for height growth from birth to 1 y (beta = 0.25
      cm(3)/SD, P < 0.0001) and 1 to 2 y (beta = 0.33 cm(3)/SD, P < 0.0001), with
      progressively weaker relationships over years 3 (beta = 0.23 cm(3)/SD, P =
      0.0002) and 4 (beta = 0.10 cm(3)/SD, P = 0.18). CONCLUSION: These results
      demonstrate that growth before age 3 y predicts proximal femoral geometry at 6 y
      old. These data suggest critical periods in which there is capacity for long-term
      influence on the later skeletal growth trajectory.

PMID- 23857298
TI  - Albendazole and its derivative JVG9 induce encystation on Giardia intestinalis
      trophozoites.
AB  - In the present study, we evaluated the effect of an albendazole (ABZ) derivative
      JVG9 on cultured Giardia intestinalis. To assess the JVG9 effects, we evaluated
      the tubulin cytoskeleton by confocal microscopy, and we found that the
      characteristic staining was modified. The scanning electron microscopy images
      revealed extremely damaged trophozoites and cyst-like cells. The confocal images
      revealed that this drug triggered the expression of cyst wall protein 1 and
      encystation. We also found that at low doses, AL triggered the encystation
      process too. 

PMID- 23857299
TI  - In vitro inhibition of methadone and oxycodone cytochrome P450-dependent
      metabolism: reversible inhibition by H2-receptor agonists and proton-pump
      inhibitors.
AB  - In vitro inhibition of oxycodone metabolism to noroxycodone and oxymorphone and R
      and S-methadone metabolism to R- and S-2-ethylidene-1,5-dimethyl-3,3
      diphenylpyrrolidine (EDDP) was measured for four H2-receptor antagonists and five
      proton-pump inhibitors (PPIs) using human liver microsomes (HLM) and cDNA
      expressed human cytochrome P450s (rCYPs). Inhibitors were first incubated with
      HLM at three concentrations with and without preincubation of inhibitor, enzyme
      source and reducing equivalents to also screen for time-dependent inhibition
      (TDI). Cimetidine and famotidine (10-1,000 uM) inhibited all the four pathways
      >50%. Nizatidine and ranitidine did not. All the five PPIs (1-200 uM) inhibited
      one or more pathways >50%. Half maximal inhibitory concentrations (IC50s) were
      then determined using rCYPs. Cimetidine and famotidine both inhibited CYP3A4
      mediated formation of noroxycodone and CYP2D6-mediated formation of oxymorphone,
      and famotidine inhibited CYP3A4-mediated formation of R- and S-EDDP, but IC50s
      were so high that only >10* therapeutic concentrations may have potential for
      reversible in vivo inhibition. The PPIs were more potent inhibitors; many have
      the potential for reversible in vivo inhibition at therapeutic concentrations.
      Omeprazole, esomeprazole and pantoprazole had greater effects on CYP3A4-mediated
      reactions, whereas lansoprazole was selective for CYP2D6-mediated formation of
      oxymorphone. Preincubation enhanced cimetidine inhibition of noroxycodone
      formation and rabeprazole inhibition of all pathways. Future studies will explore
      irreversible TDI. 

PMID- 23857300
TI  - Toxicological analyses of medications and chemicals in formalin-fixed tissues and
      formalin solutions: a review.
AB  - Toxicological analyses of medicines and chemicals in formaldehyde-treated
      specimens are a component of forensic toxicology. This review involves two parts:
      (i) reactions of formaldehyde with substances in tissues fixed with formalin
      (aqueous formaldehyde solution) and (ii) the stability of substances in formalin
      treated tissues and formalin solutions. Because it was well known that
      formaldehyde reacts with amines to form Schiff bases, it was additionally
      suggested in 1998 that formaldehyde reacts with primary and secondary amines
      together with formic acid to form N-methyl substances via the Eschweiler-Clarke
      conversion, which proceeds at room temperature. The reaction increases with pH
      and the concentration of formaldehyde. In addition, this report includes both
      experimental studies and practical cases involving embalmed bodies. 

PMID- 23857302
TI  - Flow velocities of Alaskan glaciers.
AB  - Our poor understanding of tidewater glacier dynamics remains the primary source
      of uncertainty in sea level rise projections. On the ice sheets, mass lost from
      tidewater calving exceeds the amount lost from surface melting. In Alaska, the
      magnitude of calving mass loss remains unconstrained, yet immense calving losses
      have been observed. With 20% of the global new-water sea level rise coming from
      Alaska, partitioning of mass loss sources in Alaska is needed to improve sea
      level rise projections. Here we present the first regionally comprehensive map of
      glacier flow velocities in Central Alaska. These data reveal that the majority of
      the regional downstream flux is constrained to only a few coastal glaciers. We
      find regional calving losses are 17.1 Gt a(-1), which is equivalent to 36% of the
      total annual mass change throughout Central Alaska. 

PMID- 23857303
TI  - Aquaporin 4 expression and tissue susceptibility to neuromyelitis optica.
AB  - IMPORTANCE: To understand the predilection for optic nerve and spinal cord
      pathologic changes in neuromyelitis optica (NMO). OBJECTIVE TO evaluate tissue
      specific expression (RNA and protein) and supramolecular aggregation of aquaporin
      4 (AQP4) in mouse, rat, and human tissues. DESIGN: Quantitative polymerase chain
      reaction, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and blue
      native polyacrylamide gel electrophoresis. SETTING: Laboratory analysis of mouse,
      rat, and human tissue. PARTICIPANTS: Tissues from control individuals and 1
      patient with NMO obtained at autopsy. EXPOSURE: Neuromyelitis optica in the
      patient. MAIN OUTCOMES AND MEASURES: Tissue-specific messenger RNA and protein
      expression and supramolecular aggregation of AQP4. RESULTS: The AQP4 messenger
      RNA and proteins were much more highly expressed in the optic nerve and spinal
      cord relative to other regions of the brain and to non-central nervous system
      tissues in all species evaluated. Large supramolecular aggregates of AQP4 were
      overrepresented in the optic nerve and spinal cord relative to other central
      nervous system tissue. There was no difference in AQP4 expression between an
      individual with NMO and the control samples. CONCLUSIONS AND RELEVANCE: Optic
      nerve tissue from an individual with NMO did not differ in AQP4 expression from
      control samples. The relatively high levels of expression and of supramolecular
      aggregation in the optic nerve and spinal cord may contribute to the predilection
      of these structures to NMO pathologic changes.

PMID- 23857304
TI  - Accelerated evolutionary rate of the myoglobin gene in long-diving whales.
AB  - Cetaceans, early in their evolutionary history, had developed many physiological
      adaptations to secondarily return to the sea. Among these adaptations, changes in
      molecules that transport oxygen and that ultimately support large periods of
      acute tissue hypoxia probably represent one big step toward the conquest of
      aquatic environments. Myoglobin contributes to intracellular oxygen storage and
      transcellular diffusion of oxygen in muscle, and plays an important role in
      supplying oxygen in hypoxic or ischemic conditions. Here we looked for evidence
      of adaptive molecular evolution of myoglobin in the cetacean lineage, relative to
      their terrestrial counterparts. We performed a comparative analysis to examine
      the variation of the parameter omega (d N/d S) and infer past period of adaptive
      evolution during the cetacean transition from the terrestrial to the aquatic
      environment. We also analyzed the changes in amino acid properties. At the
      nucleotide level, the results showed significant differences in selective
      pressure between cetacean and non-cetacean myoglobin (omega value three times
      higher in cetaceans when compared to terrestrial mammals), and also among
      cetacean lineages according to their diving capacities. Interestingly, both
      families with long duration diving cetaceans present two parallel substitutions
      (on sites 4 and 12). Regarding the amino acid properties, our analysis identified
      four significant physicochemical amino acid changes among residues in myoglobin
      protein under positive destabilizing selection. 

PMID- 23857306
TI  - Enhanced catalytic activity of titanosilicates controlled by hydrogen-bonding
      interactions.
AB  - A typical volcano-shaped curve has been found in heterogeneous catalytic systems
      containing titanosilicates for the first time. A new reactive intermediate with
      double H-bonds is proposed. Systematic results clearly evidence another H-bond
      formed between the high-electronegativity atom of the H-bond acceptor and the
      H(end) atom of Ti-Oalpha-Obeta-H(end).

PMID- 23857305
TI  - Association of severe intrahepatic cholestasis of pregnancy with adverse
      pregnancy outcomes: a prospective population-based case-control study.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver
      disease, characterized by maternal pruritus and raised serum bile acids. Our
      objectives were to describe the epidemiology and pregnancy complications
      associated with severe ICP and to test the hypothesis that adverse perinatal
      outcomes are increased in these women. A prospective population-based case
      control study with national coverage was undertaken using the UK Obstetric
      Surveillance System (UKOSS). Control data for comparison were obtained from women
      with healthy pregnancy outcome through UKOSS (n = 2,232), St Mary's Maternity
      Information System (n = 554,319), and Office for National Statistics (n =
      668,195). The main outcome measures investigated were preterm delivery,
      stillbirth, and neonatal unit admission. In all, 713 confirmed cases of severe
      ICP were identified, giving an estimated incidence of 9.2 per 10,000 maternities.
      Women with severe ICP and a singleton pregnancy (n = 669) had increased risks of
      preterm delivery (164/664; 25% versus 144/2200; 6.5%; adjusted odds ratio [OR]
      5.39, 95% confidence interval [CI] 4.17 to 6.98), neonatal unit admission
      (80/654; 12% versus 123/2192; 5.6%; adjusted OR 2.68, 95% CI 1.97 to 3.65), and
      stillbirth (10/664; 1.5% versus 11/2205; 0.5%; adjusted OR 2.58, 95% CI 1.03 to
      6.49) compared to controls. Seven of 10 stillbirths in ICP cases were associated
      with coexisting pregnancy complications. These differences remained significant
      against national data. Risks of preterm delivery, meconium-stained amniotic
      fluid, and stillbirth rose with increasing maternal serum bile acid
      concentrations. CONCLUSION: In the largest prospective cohort study in severe ICP
      to date, we demonstrate significant increased risks of adverse perinatal
      outcomes, including stillbirth. Our findings support the case for close antenatal
      monitoring of pregnancies affected by severe ICP.

PMID- 23857308
TI  - Neuroblastoma cells injected into experimental mature teratoma reveal a tropism
      for embryonic loose mesenchyme.
AB  - Embryonic neural tumors are responsible for a disproportionate number of cancer
      deaths in children. Although dramatic improvements in survival for pediatric
      malignancy has been achieved in previous years advancements seem to be slowing
      down. For the development of new enhanced therapy and an increased understanding
      of the disease, pre-clinical models better capturing the neoplastic niche are
      essential. Tumors of early childhood present in this respect a particular
      challenge. Here, we explore how components of the embryonic process in stem-cell
      induced mature teratoma can function as an experimental in vivo microenvironment
      instigating the growth of injected childhood neuroblastoma (NB) cell lines. Three
      human NB cell lines, IMR-32, Kelly and SK-N-BE(2), were injected into mature
      pluripotent stem cell-induced teratoma (PSCT) and compared to xenografts of the
      same cell lines. Proliferative NB cells from all lines were readily detected in
      both models with a typical histology of a poorly differentiated NB tumor with a
      variable amount of fibrovascular stroma. Uniquely in the PSCT microenvironment,
      NB cells were found integrated in a non-random fashion. Neuroblastoma cells were
      never observed in areas with well-differentiated somatic tissue i.e. bone,
      muscle, gut or areas of other easily identifiable tissue types. Instead, the
      three cell lines all showed initial growth exclusively occurring in the embryonic
      loose mesenchymal stroma, resulting in a histology recapitulating NB native
      presentation in vivo. Whether this reflects the 'open' nature of loose mesenchyme
      more easily giving space to new cells compared to other more dense tissues, the
      rigidity of matrix providing physical cues modulating NB characteristics, or if
      embryonic loose mesenchyme may supply developmental cues that attracted or
      promoted the integration of NB, remains to be tested. We tentatively hypothesize
      that mature PSCT provide an embryonic niche well suited for in vivo studies on
      NB.

PMID- 23857307
TI  - Feline foamy virus-based vectors: advantages of an authentic animal model.
AB  - New-generation retroviral vectors have potential applications in vaccination and
      gene therapy. Foamy viruses are particularly interesting as vectors, because they
      are not associated to any disease. Vector research is mainly based on primate
      foamy viruses (PFV), but cats are an alternative animal model, due to their
      smaller size and the existence of a cognate feline foamy virus (FFV). The
      potential of replication-competent (RC) FFV vectors for vaccination and
      replication-deficient (RD) FFV-based vectors for gene delivery purposes has been
      studied over the past years. In this review, the key achievements and functional
      evaluation of the existing vectors from in vitro cell culture systems to out-bred
      cats will be described. The data presented here demonstrate the broad application
      spectrum of FFV-based vectors, especially in pathogen-specific prophylactic and
      therapeutic vaccination using RD vectors in cats and in classical gene delivery.
      In the cat-based system, FFV-based vectors provide an advantageous platform to
      evaluate and optimize the applicability, efficacy and safety of foamy virus (FV)
      vectors, especially the understudied aspect of FV cell and organ tropism. 

PMID- 23857309
TI  - No effects of antidepressants on negative symptoms in schizophrenia.
AB  - Negative symptoms are common in schizophrenia, but often difficult to
      differentiate from depression. They are associated with long-term impairment and
      do not respond well to current treatment approaches. Even though antidepressants
      are commonly prescribed in schizophrenia, their beneficial effect is still under
      debate. In the present study, we aimed to investigate the effect of serotonergic
      versus noradrenergic antidepressant add-on therapy on negative symptoms in
      schizophrenia. Fifty-eight patients with schizophrenia according to Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition criteria and with
      predominant negative symptoms were randomized in a double-blind design to add-on
      treatment with citalopram, reboxetine, or placebo for 4 weeks. Analysis of
      covariance with repeated-measures design was used to compare improvement between
      treatment groups in scores of the Positive and Negative Syndrome Scale and the
      Hamilton Rating Scale for Depression. A chi2 test was used to compare responder
      rates between treatment groups. Repeated-measures analysis of covariance revealed
      no differences between treatment groups over time (treatment * time, not
      statistically significant) for Positive and Negative Syndrome Scale subscales.
      Although a subgroup analysis in subjects fulfilling the criteria for minor
      depression was suggestive of higher responder rates in the citalopram group
      compared with reboxetine, the results did not reach significance level. Our
      findings do not support a beneficial effect of adjunctive antidepressant
      treatment on negative symptoms in schizophrenia. However, depressive symptoms are
      reduced in patients with minor depression by citalopram but not reboxetine, which
      is in line with previous findings.

PMID- 23857310
TI  - A single-center, cross-sectional prevalence study of impulse control disorders in
      Parkinson disease: association with dopaminergic drugs.
AB  - The current study aimed at establishing the prevalence of impulse control
      disorders (ICDs) in patients with Parkinson disease (PD) and their association
      with demographic, drug-related, and disease-related characteristics. We performed
      a single-center cross-sectional study of 805 PD patients. Impulse control
      disorders were investigated with the Questionnaire for Impulsive Compulsive
      Disorders in Parkinson's Disease; also comorbid neuropsychiatric complications
      (dementia, delusions, visual hallucinations) were investigated with clinical
      interviews and ad hoc instruments (Parkinson Psychosis Questionnaire and
      Neuropsychiatry Inventory). Impulse control disorders were identified in 65
      patients (prevalence, 8.1%), with pathological gambling and hypersexuality the
      most frequent. Impulse control disorders were present in 57 of 593 cognitively
      preserved patients (prevalence, 9.6%) and in 8 of 212 demented patients
      (prevalence, 3.8%). Impulse control disorders were significantly associated with
      dopamine agonists (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.60
      12.46; P < 0.0001) and levodopa (OR, 2.43; 95% CI, 1.06-6.35; P = 0.034). Impulse
      control disorders frequency was similar for pramipexole and ropinirole (16.6% vs
      12.5%; OR, 1.45; 95% CI, 0.79-2.74; P = 0.227). Additional variables associated
      with ICDs were male sex and younger age. These findings suggested that
      dopaminergic treatments in PD are associated with increased odds of having an
      ICD, but also other demographic and clinical variables are associated with ICDs,
      suggesting the multifactorial nature of the ICD phenomenon in PD. 

PMID- 23857311
TI  - alpha1-Adrenergic receptors contribute to the acute effects of 3,4
      methylenedioxymethamphetamine in humans.
AB  - Preclinical studies implicate a role for alpha1-noradrenergic receptors in the
      effects of psychostimulants, including 3,4-methylenedioxymethamphetamine (MDMA,
      "ecstasy"). The present study evaluated the effects of the alpha1-noradrenergic
      receptor antagonist doxazosin on the acute pharmacodynamic and pharmacokinetic
      response to MDMA in 16 healthy subjects. Doxazosin (8 mg/d) or placebo was
      administered for 3 days before MDMA (125 mg) or placebo using a randomized,
      double-blind, placebo-controlled, 4-session, crossover design. Doxazosin reduced
      MDMA-induced elevations in blood pressure, body temperature, and moderately
      attenuated positive mood but enhanced tachycardia associated with MDMA. The
      results indicate that alpha1-adrenergic receptors contribute to the acute
      cardiostimulant and to a minor extent possibly also to the thermogenic and
      euphoric effects of MDMA in humans.

PMID- 23857312
TI  - Placebo group improvement in trials of pharmacotherapies for alcohol use
      disorders: a multivariate meta-analysis examining change over time.
AB  - OBJECTIVE: Placebo group improvement in pharmacotherapy trials has been
      increasing over time across several pharmacological treatment areas. However, it
      is unknown to what degree increasing improvement has occurred in pharmacotherapy
      trials for alcohol use disorders or what factors may account for placebo group
      improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated
      (1) the magnitude of placebo group improvement, (2) the extent to which placebo
      group improvement has been increasing over time, and (3) several potential
      moderators that might account for variation in placebo group improvement. METHOD:
      Random-effects univariate and multivariate analyses were conducted that examined
      the magnitude of placebo group improvement in the 47 studies and several
      potential moderators of improvement: (a) publication year, (b) country in which
      the study was conducted, (c) outcome data source/type, (d) number of placebo
      administrations, (e) overall severity of study participants, and (f) additional
      psychosocial treatment. RESULTS: Substantial placebo group improvement was found
      overall and improvement was larger in more recent studies. Greater improvement
      was found on moderately subjective outcomes, with more frequent administrations
      of the placebo, and in studies with greater participant severity of illness.
      However, even after controlling for these moderators, placebo group improvement
      remained significant, as did placebo group improvement over time. CONCLUSIONS:
      Similar to previous pharmacotherapy placebo research, substantial pretest to
      posttest placebo group improvement has occurred in alcohol pharmacotherapy
      trials, an effect that has been increasing over time. However, several plausible
      moderator variables were not able to explain why placebo group improvement has
      been increasing over time.

PMID- 23857313
TI  - Transcranial direct current stimulation enhances recovery of stereopsis in adults
      with amblyopia.
AB  - Amblyopia is a neurodevelopmental disorder of vision caused by abnormal visual
      experience during early childhood that is often considered to be untreatable in
      adulthood. Recently, it has been shown that a novel dichoptic videogame-based
      treatment for amblyopia can improve visual function in adult patients, at least
      in part, by reducing inhibition of inputs from the amblyopic eye to the visual
      cortex. Non-invasive anodal transcranial direct current stimulation has been
      shown to reduce the activity of inhibitory cortical interneurons when applied to
      the primary motor or visual cortex. In this double-blind, sham-controlled cross
      over study we tested the hypothesis that anodal transcranial direct current
      stimulation of the visual cortex would enhance the therapeutic effects of
      dichoptic videogame-based treatment. A homogeneous group of 16 young adults (mean
      age 22.1 +/- 1.1 years) with amblyopia were studied to compare the effect of
      dichoptic treatment alone and dichoptic treatment combined with visual cortex
      direct current stimulation on measures of binocular (stereopsis) and monocular
      (visual acuity) visual function. The combined treatment led to greater
      improvements in stereoacuity than dichoptic treatment alone, indicating that
      direct current stimulation of the visual cortex boosts the efficacy of dichoptic
      videogame-based treatment. This intervention warrants further evaluation as a
      novel therapeutic approach for adults with amblyopia. 

PMID- 23857314
TI  - Vitamin D 2 interacts with Human PrP(c) (90-231) and breaks PrP(c)
      oligomerization in vitro.
AB  - PrP(sc), the pathogenic isoform of PrP(c), can convert PrP(c) into PrP(sc)
      through direct interactions. PrP(c) oligomerization is a required processing step
      before PrP(sc) formation, and soluble oligomers appear to be the toxic species in
      amyloid-related disorders. In the current study, direct interactions between
      vitamin D 2 and human recombinant PrP(c) (90-231) were observed by Biacore assay,
      and 3F4 antibody, specific for amino acid fragment 109-112 of PrP(c), inhibited
      this interaction. An ELISA study using3F4 antibody showed that PrP(c) (101-130),
      corresponding sequence to human PrP, was affected by vitamin D 2, supporting the
      results of Biacore studies and suggesting that the PrP(c) sequence around the 3F4
      epitope was responsible for the interaction with vitamin D 2. Furthermore, the
      effects of vitamin D 2 on disruption of PrP(c) (90-231) oligomerization were
      elucidated by dot blot analysis and differential protease k susceptibilities.
      While many chemical compounds have been proposed as potential therapeutic agents
      for the treatment of scrapie, most of these are toxic. However, given the safety
      and blood brain barrier permeability of vitamin D 2, we propose that vitamin D 2
      may be a suitable agent to target PrP(c) in the brain and therefore is a
      potential therapeutic candidate for prion disease. 

PMID- 23857316
TI  - Continuous femoral nerve block using 0.125% bupivacaine does not prevent early
      ambulation after total knee arthroplasty.
AB  - BACKGROUND: Continuous femoral nerve block has been shown to decrease opioid use,
      improve postoperative pain scores, and decrease length of stay. However, several
      studies have raised the concern that continuous femoral nerve block may delay
      patient ambulation and increase the risk of falls during the postoperative
      period. QUESTIONS/PURPOSES: This study sought to determine whether continuous
      femoral nerve block with a single-shot sciatic block prevented early ambulation
      after total knee arthroplasty (TKA) and whether the technique was associated with
      adverse effects. METHODS: Between January 2011 and January 2013, 77 consecutive
      patients undergoing primary TKAs at an orthopaedic specialty hospital received a
      continuous femoral nerve block for perioperative analgesia. The femoral block was
      placed preoperatively with an initial bolus and 76 (99%) patients received a
      single-shot sciatic nerve block performed at the same time. Fifty-eight percent
      (n = 45) received an initial bolus of 0.125% bupivacaine and 42% (n = 32)
      received 0.25% bupivacaine. All 77 patients received 0.125% bupivacaine infusion
      postoperatively with the continuous femoral nerve block. All patients were
      provided a knee immobilizer that was worn while they were out of bed and was used
      until 24 hours after removal of the block. All patients also used a front-wheeled
      walker to assist with ambulation. All 77 patients had complete records for
      assessing the end points of interest in this retrospective case series, including
      distance ambulated each day and whether in-hospital complications could be
      attributed to the patients' nerve blocks. RESULTS: Thirty-five patients (45%)
      ambulated for a mean distance of 19 +/- 22 feet on the day of surgery. On
      postoperative Days 1 and 2, all 77 patients successfully ambulated a mean of 160
      +/- 112 and 205 +/- 123 feet, respectively. Forty-eight patients (62%) had
      documentation of ascending/descending stairs during their hospital stay. No
      patient fell during the postoperative period, required return to the operating
      room, or readmission within 90 days of surgery. One patient experienced a
      transient foot drop related to the sciatic nerve block, which resolved by
      postoperative Day 1. CONCLUSIONS: Continuous femoral nerve block with dilute
      bupivacaine (0.125%) can be successfully used after TKA without preventing early
      ambulation. By taking active steps to prevent in-hospital falls, including the
      use of a knee immobilizer for ambulation while the block is in effect, patients
      can benefit from the analgesia provided by the block and still ambulate early
      after TKA. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 23857317
TI  - Professional liability in orthopaedics and traumatology in Italy.
AB  - BACKGROUND: Interest in medical errors has increased during the last few years
      owing to the number of medical malpractice claims. Reasons for the increasing
      number of claims may be related to patients' higher expectations, iatrogenic
      injury, and the growth of the legal services industry. Claims analysis provides
      helpful information in specialties in which a higher number of errors occur,
      highlighting areas where orthopaedic care might be improved. QUESTIONS/PURPOSES:
      We determined: (1) the number of claims involving orthopaedics and traumatology
      in Rome; (2) the risk of litigation in elective and trauma surgery; (3) the most
      common surgical procedures involved in claims and indemnity payments; (4) the
      time between the adverse medical event and the judgment date; and (5) issues
      related to informed consent. METHODS: We analyzed 1925 malpractice judgments
      decided in the Civil Court of Rome between 2004 and 2010. RESULTS: In total, 243
      orthopaedics claims were filed, and in 75% of these cases surgeons were found
      liable; 149 (61%) of these resulted from elective surgery. Surgical teams were
      sued in 30 claims and found liable in 22. The total indemnity payment ordered was
      more than ?12,350,000 (USD 16,190,000). THA and spinal surgery were the most
      common surgical procedures involved. Inadequate informed consent was reported in
      5.3% of cases. CONCLUSIONS: Our study shows that careful medical examination,
      accurate documentation in medical records, and adequate informed consent might
      reduce the number of claims. We suggest monitoring of court judgments would be
      useful to develop prevention strategies to reduce claims.

PMID- 23857318
TI  - Exploring the chemical space of aromatase inhibitors.
AB  - Aromatase, a rate-limiting enzyme catalyzing the conversion of androgen to
      estrogen, is overexpressed in human breast cancer tissue. Aromatase inhibitors
      (AIs) have been used for the treatment of estrogen-dependent breast cancer in
      post-menopausal women by blocking the biosynthesis of estrogen. The undesirable
      side effects in current AIs have called for continued pursuit for novel
      candidates with aromatase inhibitory properties. This study explores the chemical
      space of all known AIs as a function of their physicochemical properties by means
      of univariate (i.e., statistical and histogram analysis) and multivariate (i.e.,
      decision tree and principal component analysis) approaches in order to understand
      the origins of aromatase inhibitory activity. Such a non-redundant set of AIs
      spans a total of 973 compounds encompassing both steroidal and non-steroidal
      inhibitors. Substructure analysis of the molecular fragments provided pertinent
      information on the structural features important for ligands providing high and
      low aromatase inhibition. Analyses were performed on data sets stratified
      according to their structural scaffolds (i.e., steroids and non-steroids) and
      bioactivities (i.e., actives and inactives). These analyses have uncover a set of
      rules characteristic to active and inactive AIs as well as revealing the
      constituents giving rise to potent aromatase inhibition. 

PMID- 23857319
TI  - Rosiglitazone and cardiovascular outcomes: is there a clear answer?

PMID- 23857320
TI  - Rosiglitazone and outcomes for patients with diabetes mellitus and coronary
      artery disease in the Bypass Angioplasty Revascularization Investigation 2
      Diabetes (BARI 2D) trial.
AB  - BACKGROUND: Rosiglitazone improves glycemic control for patients with type 2
      diabetes mellitus, but there remains controversy regarding an observed
      association with cardiovascular hazard. The cardiovascular effects of
      rosiglitazone for patients with coronary artery disease remain unknown. METHODS
      AND RESULTS: To examine any association between rosiglitazone use and
      cardiovascular events among patients with diabetes mellitus and coronary artery
      disease, we analyzed events among 2368 patients with type 2 diabetes mellitus and
      coronary artery disease in the Bypass Angioplasty Revascularization Investigation
      2 Diabetes (BARI 2D) trial. Total mortality, composite death, myocardial
      infarction, and stroke, and the individual incidence of death, myocardial
      infarction, stroke, congestive heart failure, and fractures, were compared during
      4.5 years of follow-up among patients treated with rosiglitazone versus patients
      not receiving a thiazolidinedione by use of Cox proportional hazards and Kaplan
      Meier analyses that included propensity matching. After multivariable adjustment,
      among patients treated with rosiglitazone, mortality was similar (hazard ratio
      [HR], 0.83; 95% confidence interval [CI], 0.58-1.18), whereas there was a lower
      incidence of composite death, myocardial infarction, and stroke (HR, 0.72; 95%
      CI, 0.55-0.93) and stroke (HR, 0.36; 95% CI, 0.16-0.86) and a higher incidence of
      fractures (HR, 1.62; 95% CI, 1.05-2.51); the incidence of myocardial infarction
      (HR, 0.77; 95% CI, 0.54-1.10) and congestive heart failure (HR, 1.22; 95% CI,
      0.84-1.82) did not differ significantly. Among propensity-matched patients, rates
      of major ischemic cardiovascular events and congestive heart failure were not
      significantly different. CONCLUSIONS: Among patients with type 2 diabetes
      mellitus and coronary artery disease in the BARI 2D trial, neither on-treatment
      nor propensity-matched analysis supported an association of rosiglitazone
      treatment with an increase in major ischemic cardiovascular events. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00006305.

PMID- 23857321
TI  - Impact of percutaneous coronary intervention performance reporting on cardiac
      resuscitation centers: a scientific statement from the American Heart
      Association.

PMID- 23857323
TI  - Rev1 is essential in generating G to C transversions downstream of the Ung2
      pathway but not the Msh2+Ung2 hybrid pathway.
AB  - Somatic hypermutation (SHM) and class switch recombination (CSR) of
      immunoglobulin (Ig) genes are initiated by the enzymatic deamination of cytosine
      (C) to uracil (U). Uracil-DNA-glycosylase (Ung2) converts uracils into
      apyrimidinic (AP) sites, which is essential for the generation of transversions
      (TVs) at G/C basepairs during SHM and for efficient DNA break formation during
      CSR. Besides Ung2, the mismatch repair protein Msh2 and the translesion synthesis
      (TLS) DNA polymerase (Pol) Rev1 are implicated in SHM and CSR. To further unravel
      the role of Rev1, we studied WT, Rev1-deficient, Msh2-deficient, and Rev1, Msh2
      double-deficient B cells. Loss of Rev1 only slightly reduced CSR. During SHM G/C
      to C/G TVs are generated in both Ung2- and Ung+Msh2-dependent fashions. We found
      that Rev1 is essential for the Msh2-independent generation of these TVs
      downstream of Ung2-induced AP sites. In the Ung+Msh2 hybrid pathway, Rev1 is not
      essential and can be substituted by an alternative TLS Pol, especially when Rev1
      is lacking. 

PMID- 23857324
TI  - Chronic pain following inguinal hernia repair: assessment of quality of life and
      medico-legal aspects.
AB  - The aim of our study was to evaluate the quality of life (QoL) of a group of
      patients who underwent tension-free inguinal hernia repair in light of the
      possible medicolegal implications. We conducted a retrospective study on the QoL
      of patients who underwent inguinal hernioplasty. One hundred and fifty patients
      who answered the SF-36 questionnaire were included in the study. Twenty-six
      (17.3%) had chronic pain, 18 (12%), sensory deficits, and 106 (70.6%) did not
      complain of any symptoms. There was no a significant deterioration in QoL
      compared to the reference population. In the group with chronic pain, 10 patients
      (38.4%) reported being very limited in performing "physically demanding
      activities"; 18 (69.2%) reported a deficit of performance in activities of daily
      living; 8 (30.7%) complained of a reduction of time spent at work because of
      emotional disorders. In one case the pain was particularly severe and required
      surgical treatment. The answers obtained through the questionnaire show that
      tension-free hernioplasty does not degrade patients'QoL. However in the group of
      patients with chronic pain examined one year after surgery, QoL had deteriorated
      so much that it affected the employment sphere and the social and relational
      sphere. Although there is a relatively low incidence and frequency of problems
      relating to chronic pain following inguinal hernioplasty, chronic pain can
      sometimes have serious effects on QoL and socio-economic and legal implications.

PMID- 23857325
TI  - Unidirectional self-assembly of soft templated mesoporous carbons by zone
      annealing.
AB  - Surfactant or block copolymer-templated mesoporous films have been extensively
      explored, but achieving mesostructure coherence and unidirectional orientation
      over macroscopic dimensions has remained quite challenging for these self
      assembled systems. Here, we extend the concepts associated with zone refinement
      of crystalline materials to soft templated mesoporous carbon films based on the
      cooperative assembly of commercial non-ionic surfactants (block copolymers) and
      phenolic resin oligomers (resol) to provide macroscopic alignment of both cubic
      (FDU-16) and hexagonal (FDU-15) mesostructures. The average orientation of these
      mesophases is determined from rotation grazing incidence small angle X-ray
      scattering (GISAXS) measurements. For FDU-15 templated by Pluronic P123, the
      orientation factor for the zone-annealed film is 0.98 based on the average of the
      second Legendre polynomial, but this orientation deteriorates significantly
      during carbonization. Notably, a thermal stabilization step following zone
      annealing preserves the orientation of the mesostructure during carbonization.
      The orientation factor for an isotropic cubic structure (FDU-16 templated by
      Pluronic F127) is only 0.48 (based on the 111 reflection with incident angle 0.15
      degrees ) for the same zone annealing protocol, but this illustrates the
      versatility of zone annealing to different mesostructures. Unexpectedly, zone
      annealing of FDU-15 templated by Pluronic F127 leads to stabilization of the
      mesostructure through carbonization, whereas this structure collapses fully
      during carbonization even after extended oven annealing; despite no clear
      macroscopic orientation of the cylindrical mesostructure from zone annealing.
      Thermal zone annealing provides a simple methodology to produce highly ordered
      and macroscopically oriented stable mesoporous carbon films, but the efficacy is
      strongly tied to the mobility of the template during the zone annealing. 

PMID- 23857327
TI  - Challenges in treating prosthetic valve endocarditis.

PMID- 23857328
TI  - Potential role of oxidative stress on the prescription of rehabilitation
      interventions in spinal cord injury.
AB  - STUDY DESIGN: Review article. OBJECTIVES: To provide an overview of free radical
      biology, particularly with respect to muscle physiology, as well as the potential
      effects of muscle morphological changes, physical capacity and nutritional status
      on oxidative stress in people with chronic spinal cord injury (SCI). The
      potential implications of these factors for determining the optimal dosage of
      rehabilitation training interventions in people with chronic SCI will also be
      presented. SETTING: Vancouver, BC, Canada. METHODS: Literature review. RESULTS:
      Not applicable. CONCLUSION: There has been a great deal of focus on
      rehabilitation exercise interventions providing intensive practice of movements
      to enhance functional recovery and physical capacity following SCI. However,
      there is still much to be understood about the appropriate dosage of training
      parameters (e.g. frequency, duration). It has been known for several decades that
      exercise increases free radical production, leading to oxidative stress. To date,
      there has been little consideration of the potential interaction of oxidative
      stress with training parameters on functional outcomes in chronic SCI.
      Furthermore, individuals with chronic SCI face many secondary consequences of
      their injury, such as muscle atrophy, change in muscle fiber type, general
      deconditioning and nutritional status, that are known to influence free radical
      production and antioxidant capacity. Better understanding of the potential
      confounding effects of oxidative stress associated with exercise will improve our
      ability to determine the optimal 'dose' of rehabilitation training to maximize
      functional recovery following SCI.

PMID- 23857329
TI  - Premature aging, allostasis and restorgenesis.

PMID- 23857330
TI  - A stabilizing factor for mitochondrial respiratory supercomplex assembly
      regulates energy metabolism in muscle.
AB  - The mitochondrial respiratory chain is essential for oxidative phosphorylation
      and comprises multiple complexes, including cytochrome c oxidase, assembled in
      macromolecular supercomplexes. Little is known about factors that contribute to
      supercomplex organization. Here we identify COX7RP as a factor that promotes
      supercomplex assembly. Cox7rp-knockout mice exhibit decreased muscular activity
      and heat production failure in the cold due to reduced COX activity. In contrast,
      COX7RP-transgenic mice exhibit increased exercise performance with increased
      cytochrome c oxidase activity. Two-dimensional blue native electrophoresis
      reveals that COX7RP is a key molecule that promotes assembly of the III2/IVn
      supercomplex with complex I. Our study identified COX7RP as a protein that
      functions in I/III2/IVn supercomplex assembly and is required for full activity
      of mitochondrial respiration. 

PMID- 23857331
TI  - An individualized weight-based goal urine volume model significantly improves
      expected calcium concentrations relative to a 2-L goal urine volume.
AB  - Increased urinary volume decreases recurrence rates of nephrolithiasis. Current
      recommendations for goal volumes are not adjusted to reflect individual risk
      factors, such as obesity. Our intent was to develop and evaluate a goal urine
      volume for stone prevention based on predictive calcium modeling. Stone formers
      with a 24-h urine study (6/2001-9/2010) were identified. Patients with inadequate
      collections or non-calcium stones were excluded. Multivariate and univariate
      predictive models for daily calcium were evaluated and a univariate (weight)
      model was selected. A target calcium concentration constant (2.5 mM) was
      determined from current recommendations. Individualized weight-based goal urine
      volumes (WGUV) were calculated. Measured calcium concentration and expected
      calcium concentrations using a 2-L goal volume and WGUV were compared. 185 of 399
      patients met inclusion criteria. Body weight was a strong predictor of calcium
      excretion in each model (p < 0.0001). While a 2-L goal urine volume would be
      expected to improve mean calcium concentrations for the cohort from 3.53 to 2.96
      mM, the benefit is unequal between subsets with nearly twofold expected
      concentration for the highest weight quartile (3.98 vs. 2.10 mM) and higher
      expected concentration for males (3.35 vs. 2.59 mM). By contrast, a WGUV model
      improves expected concentrations for all subsets to <2.9 mM and the overall
      cohort to 2.50 mM. This study demonstrates a strong relationship between body
      weight and urinary calcium excretion in stone formers. We introduce the novel
      concept of individualized goal urine output using statistical modeling, which may
      be preferable to current recommendations. 

PMID- 23857332
TI  - Theiler's murine encephalomyelitis virus as an experimental model system to study
      the mechanism of blood-brain barrier disruption.
AB  - Theiler's murine encephalomyelitis virus is a widely used model to study the
      initiation and progression of multiple sclerosis. Many researchers have used this
      model to investigate how the immune system and genetic factors contribute to the
      disease process. Current research has highlighted the importance of cytotoxic CD8
      T cells and specific major histocompatibility complex (MHC) class I alleles. Our
      lab has adopted this concept to create a novel mouse model to study the mechanism
      of blood-brain barrier (BBB) disruption, an integral feature of numerous
      neurological disorders. We have demonstrated that epitope-specific CD8 T cells
      cause disruption of the tight junction architecture and ensuing CNS vascular
      permeability in the absence of neutrophil support. This CD8 T cell-initiated BBB
      disruption is dependent on perforin expression. We have also elucidated a
      potential role for hematopoietic factors in this process. Despite having
      identical MHC class I molecules, similar inflammation in the CNS, and equivalent
      ability to utilize perforin, C57BL/6 mice are highly susceptible to this
      condition, while 129 SvIm mice are resistant. This susceptibility is transferable
      with the bone marrow compartment. These findings led us to conduct a
      comprehensive genetic analysis which has revealed a list of candidate genes
      implicated in regulating traits associated with BBB disruption. Future studies
      will continue to define the underlying molecular mechanism of CD8 T cell
      initiated BBB disruption and may assist in the development of potential
      therapeutic approaches to ameliorate pathology associated with BBB disruption in
      neurological disorders. 

PMID- 23857333
TI  - Regulation of FOXO3 by phosphorylation and methylation in hepatitis C virus
      infection and alcohol exposure.
AB  - Hepatitis C virus (HCV) infection produces chronic liver injury that is
      significantly exacerbated by alcohol consumption. While multiple mechanisms
      contribute to this synergy, a viral-induced loss of antioxidant responses has
      been shown to play an important role. This study examined the effects of HCV
      infection and alcohol on the regulation of the transcription factor FOXO3, an
      important regulator of Mn-superoxide dismutase (SOD2) expression, a tumor
      suppressor, and a component of the hepatic antioxidant response system. FOXO3 was
      activated by either HCV or alcohol alone but suppressed by the combination. To
      understand this paradoxical result, we applied a capillary isoelectric focusing
      (IEF) method to determine the pattern of FOXO3 posttranslational modifications
      (PTMs) induced by HCV and alcohol. We observed the presence of multiple different
      nuclear and cytosolic species of FOXO3 and used antiphosphoserine, acetyl-lysine,
      methylarginine, and ubiquitin antibodies to identify the PTM patterns present in
      each species. HCV caused multiple changes including phosphorylation of FOXO3 at S
      574, a novel c-Jun N-terminal kinase (JNK) site, which promoted nuclear
      translocation and transcription. Ethanol suppressed arginine-methylation of FOXO3
      promoting nuclear export and degradation of the JNK phosphorylated form. Human
      liver biopsy samples showed the presence of the HCV-specific form of FOXO3 in HCV
      infected livers but not in normal liver or nonalcoholic steatohepatitis.
      CONCLUSION: The development of this novel IEF method for the simultaneous
      quantification of differently modified FOXO3 species allowed us to demonstrate
      how HCV and alcohol combine to modify a complex pattern of FOXO3 PTMs that
      contribute to pathogenesis. This approach will allow further dissection of the
      role of protein PTMs in viral liver disease.

PMID- 23857334
TI  - Continuous support for women during childbirth.
AB  - BACKGROUND: Historically, women have been attended and supported by other women
      during labour. However, in hospitals worldwide, continuous support during labour
      has become the exception rather than the routine. OBJECTIVES: Primary: to assess
      the effects of continuous, one-to-one intrapartum support compared with usual
      care. Secondary: to determine whether the effects of continuous support are
      influenced by: (1) routine practices and policies; (2) the provider's
      relationship to the hospital and to the woman; and (3) timing of onset. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 May 2013). SELECTION CRITERIA: All published and unpublished
      randomised controlled trials comparing continuous support during labour with
      usual care. DATA COLLECTION AND ANALYSIS: We used standard methods of The
      Cochrane Collaboration Pregnancy and Childbirth Group. Two review authors
      independently evaluated methodological quality and extracted the data. We sought
      additional information from the trial authors. We used random-effects analyses
      for comparisons in which high heterogeneity was present, and we reported results
      using the average risk ratio (RR) for categorical data and mean difference (MD)
      for continuous data. MAIN RESULTS: Twenty-two trials involving 15,288 women met
      inclusion criteria and provided usable outcome data. Results are of random
      effects analyses, unless otherwise noted. Women allocated to continuous support
      were more likely to have a spontaneous vaginal birth (RR 1.08, 95% confidence
      interval (CI) 1.04 to 1.12) and less likely to have intrapartum analgesia (RR
      0.90, 95% CI 0.84 to 0.96) or to report dissatisfaction (RR 0.69, 95% CI 0.59 to
      0.79). In addition, their labours were shorter (MD -0.58 hours, 95% CI -0.85 to 
      0.31), they were less likely to have a caesarean (RR 0.78, 95% CI 0.67 to 0.91)
      or instrumental vaginal birth (fixed-effect, RR 0.90, 95% CI 0.85 to 0.96),
      regional analgesia (RR 0.93, 95% CI 0.88 to 0.99), or a baby with a low five
      minute Apgar score (fixed-effect, RR 0.69, 95% CI 0.50 to 0.95). There was no
      apparent impact on other intrapartum interventions, maternal or neonatal
      complications, or breastfeeding. Subgroup analyses suggested that continuous
      support was most effective when the provider was neither part of the hospital
      staff nor the woman's social network, and in settings in which epidural analgesia
      was not routinely available. No conclusions could be drawn about the timing of
      onset of continuous support. AUTHORS' CONCLUSIONS: Continuous support during
      labour has clinically meaningful benefits for women and infants and no known
      harm. All women should have support throughout labour and birth.

PMID- 23857335
TI  - Primary alveolar rhabdomyosarcoma of the brain with long-term survival.

PMID- 23857338
TI  - Chromosome aberrations and gene mutations in patients with esophageal atresia.
AB  - Esophageal atresia (EA) is one of the most frequent congenital malformations of
      the gastrointestinal tract. Many genetic alterations in patients with EA have
      been described in the literature. It is thought that the etiology of EA is
      heterogeneous. This review of the literature provides detailed information about
      chromosomal aberrations, gene mutations, and clinical features of neonates with
      EA, and serves as an excellent source to compare newly diagnosed patients with
      those described in the literature. 

PMID- 23857337
TI  - Separation and characterization of nitrated variants of the major birch pollen
      allergen by CZE-ESI-MUTOF MS.
AB  - A CZE-ESI-TOF MS method has been optimized for the separation and identification
      of nitrated variants of the major birch pollen allergen from Betula verrucosa,
      isoform 1a (Bet v 1a). In-house nitration of recombinant Bet v 1a was done by
      peroxynitrite. As a BGE, 10 mmol/L ammonium bicarbonate with pH 7.50 provided
      best resolution. Nebulizer gas pressure and sheath liquid flow rate of 0.4 bar
      and 6 MUL/min, respectively, maintained CZE selectivity and constituted stable
      electrospray conditions. A sheath liquid composition of 75% v/v methanol with
      0.1% v/v formic acid in ultrapure water resulted in highest signal intensities.
      Alternatively, methanol could be replaced by 50% v/v isopropanol. Two modified
      allergen products derived from reaction mixtures that contained different amounts
      of the nitration reagent were compared by the elaborated CZE-ESI-TOF MS method.
      Up to twelve different Bet v 1a variants with one- to sixfold nitration could be
      distinguished. Several allergen fractions of equivalent nitration grade were
      resolved. Their different migration times indicate site-specific nitration with
      concomitant differences in pI and maybe also in hydrodynamic radius. The method
      allows for a characterization of in-house nitrated allergen samples that are
      intended for testing the postulated enhanced allergenicity of nitrated Bet v 1a
      variants. 

PMID- 23857339
TI  - Assessment of abdominal pain through global outcomes and recent FDA
      recommendations in children: are we ready for change?
AB  - OBJECTIVES: Irritable bowel syndrome is a multisymptom construct, with abdominal
      pain (AP) acting as the driving symptom of patient-reported severity. The Food
      and Drug Administration considers a >30% decrease in AP as satisfactory
      improvement, but this has not been validated in children. We investigated the
      correspondence of 2 measures for AP assessment, >=30% improvement in AP and
      global assessment of improvement. METHODS: Secondary analysis of data from 72
      children who completed a randomized clinical trial for abdominal pain-associated
      functional gastrointestinal disorders. Children completed daily assessment of AP
      intensity, functional disability inventory (FDI), question regarding pain's
      interference with activities, and 2 global assessment questions. We measured the
      extent to which >=30% improvement of AP and global assessment questions
      correlated with each other and with disability. RESULTS: The global questions
      correlated with each other (r=0.74; P<0.0001) and with a >=30% improvement in AP
      (P<0.01). Global outcomes were satisfaction with treatment was inversely related
      to the child's report of interference with activities (P<0.01) and symptom relief
      was positively associated with >=30% improvement in FDI scores (P<0.009). A 30%
      change in FDI scores was associated with global questions of symptom relief
      (P=0.009) but not with satisfaction with treatment (P=0.07). The association of
      AP improvement with interference with activities (P=0.14) or change in FDI scores
      (P=0.27) did not reach significance. CONCLUSIONS: Currently used global
      assessments are significantly associated with decreased pain intensity, decreased
      interference with daily activities, and a >=30% change in FDI scores, whereas
      recommended 30% improvement in pain intensity is not as comprehensive.

PMID- 23857340
TI  - Effect of fortifiers and additional protein on the osmolarity of human milk: is
      it still safe for the premature infant?
AB  - OBJECTIVES: The present guidelines of the American Academy of Pediatrics
      recommend that osmolarity not exceed 450 mOsm/kg (or approximately an osmolarity
      of 400 mOsm/L) for breast milk or infant formulae, to minimize the risk factors
      for necrotizing enterocolitis. A commercial protein supplement has been developed
      to meet special protein requirements (4.0-4.5 g . kg(-1) . day(-1)) of infants
      with a birth weight <1000 g. Because its effect on osmolarity has not been
      systematically studied, we characterized the effects of fortification on the
      osmolarity of human milk (HM). METHODS: Osmolarity of fresh and processed HM was
      measured at baseline, after fortification with a commercial HM fortifier and
      after further supplementation with additional protein increasing in 0.5-g steps
      up to 4.0 g. Measurements were performed immediately after adding fortifier
      and/or protein and after 24 hours. In addition, changes in osmolarity were
      determined after adding therapeutic additives such as iron, multivitamin
      supplement, and calcium-phosphorus capsules. RESULTS: Native HM samples (n = 84)
      had 297 mOsm/L, (median; 95% confidence interval 295-299 mOsm/L). Adding HM
      fortifier increased osmolarity up to 436 mOsm/L (95% confidence interval 431-441
      mOsm/L). Additional protein supplementation increased osmolarity by 23.5 mOsm/L
      per 0.5-g step, up to a maximum of 605 mOsm/L. Pasteurization decreased
      osmolarity by 20-30 mOsm/L (P < 0.001), and storage for 24 hours slightly
      increased osmolarity (by 11.5 mOsm/L P = 0.0002). Therapeutic additives increased
      osmolarity up to 868 mOsm/L. CONCLUSIONS: Adding HM fortifier and additional
      protein to HM increased osmolarity to >400 mOsm/L and therefore above the
      recommended threshold. Because of the excessive increase in osmolarity
      combinations of HM + fortifier and additional protein should not be applied
      together with multivitamins or other additives.

PMID- 23857341
TI  - Potential for improving therapy and defining new research targets in eosinophilic
      oesophagitis based on understanding of immunopathogenesis.
AB  - OBJECTIVES: This review considers the potential for therapeutic advances in the
      management of eosinophilic oesophagitis (EoE) based on recently increased
      understanding of the pathophysiology of the disorder. METHODS: This is a review
      of publications characterising mucosal changes and leucocyte recruitment patterns
      in human and experimental EoE. RESULTS: EoE, although diagnosed by epithelial
      infiltration of eosinophils, is actually a transmural inflammation in which
      eosinophil recruitment occurs via the deeper layers. Penetration of eosinophils
      into the epithelium is variable, explaining the need for multiple biopsies to
      diagnose what may be a clearly visible disorder. Fibrosis and neuromuscular
      dysfunction both occur within the subepithelial tissues. Recent murine studies
      have identified that T-cell recruitment underpins antigen-specific oesophageal
      eosinophil recruitment. Involvement of innate immunity is also suggested by the
      role of invariant natural killer T cells in experimental EoE. CONCLUSIONS:
      Looking beyond present therapeutic options with a view to future studies, we
      identify T cells as candidates for "upstream therapy" if antigen specificity or
      homing markers are determined. Evidence of aeroallergen sensitisation suggests
      the possibility of lymphocyte priming within nasal-associated lymphoid tissue or
      Waldeyer ring, with the potential for topical therapy. We consider acquired
      neuromuscular dysfunction as a therapeutic target in acute symptomatic
      deterioration or bolus obstruction. We assess possible similarities with
      therapeutic stratagems for chronic asthma, recognising at the same time the
      anatomic specificity of the oesophagus and the difficulty in delivering effective
      topical medication to subepithelial tissues in this location compared with the
      airway.

PMID- 23857342
TI  - Preschool physical activity and functional constipation: the Generation R study.
AB  - OBJECTIVES: Decreased physical activity levels in children may partly explain the
      rising prevalence of functional constipation in childhood. The aim of the present
      study, therefore, was to examine the association between physical activity and
      functional constipation during the preschool period. METHODS: This study was
      embedded in the Generation R study, a large prospective birth-cohort study in
      Rotterdam, The Netherlands. Physical activity was measured by an Actigraph
      accelerometer in 347 children (182 boys, 165 girls; mean age 25.1 months) and
      data were expressed as counts per minute. Data were categorized into light
      activity (302-614 counts/15 seconds), moderate activity (615-1230 counts/15
      seconds), and vigorous activity (>=1231 counts/15 seconds). Functional
      constipation in the third and fourth year of life was defined according to the
      Rome II criteria. RESULTS: Children spending time in the highest tertile of light
      (adjusted odds ratio [OR] 0.34; 95% confidence interval [CI] 0.13-0.87), moderate
      (adjusted OR 0.37; 95% CI 0.14-0.97), and total activity (adjusted OR 0.37; 95%
      CI 0.15-0.92) at the age of 2 years had significantly less functional
      constipation in the fourth year of life. For functional constipation in the third
      year of life, the results were in similar direction but not statistically
      significant. Additionally, children with physical activity of more than the WHO
      recommendation of 60 min/day had significantly less functional constipation in
      the fourth year of life (adjusted OR 0.48; 95% CI 0.24-0.97). CONCLUSIONS:
      Physical activity is associated with a decreased risk of functional constipation
      in the preschool period, but this may be time dependent.

PMID- 23857343
TI  - The winding road to understanding the neonatal origins of inflammatory
      gastrointestinal disorders.
AB  - Beginning with the observation that birth weight correlates with increased risk
      of cardiovascular disease, the concept of neonatal programming, that the
      environmental influence on fetal and neonatal development results in modification
      of the risk profile for adult disease, has begun to emerge as an important
      component to understanding the origin of chronic diseases of many different organ
      systems. Until recently, the gastrointestinal system has not been considered. Our
      understanding of the pathogenesis of many intestinal inflammatory disorders is
      still incomplete; however, a brief review of what is known reveals several
      opportunities for the early intraluminal environment to affect the development of
      the intestinal immune system. Early clinical observations such as the increased
      risk of celiac disease observed in those born by cesarean section and the
      protective effect of breast-feeding against inflammatory bowel disease and celiac
      disease support the role of neonatal programming in the development of chronic
      inflammatory gastrointestinal disease. Additional, more robust clinical studies
      are needed to confirm this role. Furthermore, examination of the possible
      mechanisms of immune phenotype modification is necessary. 

PMID- 23857344
TI  - CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and
      metastasis in pancreatic cancer.
AB  - Pancreatic cancer is a disease with an extremely poor prognosis. The acquisition
      of invasion properties in pancreatic cancer is accompanied by the process of
      epithelial-mesenchymal transition (EMT). Carcinoembryonic antigen-related cell
      adhesion molecule 6 (CEACAM6) is emerging as an important determinant of the
      malignant phenotype in a range of cancers, including pancreatic cancer.
      Therefore, the aim of this study was to evaluate the potential involvement of
      CEACAM6 in the invasion and metastasis of pancreatic cancer cells via EMT
      regulation. The results of our study showed a positive association between
      CEACAM6 expression and poor prognosis of pancreatic cancer, differentiation and
      lymph node metastasis. Elevated levels of CEACAM6 in pancreatic cancer cells
      promoted EMT, migration and invasion in vitro and metastasis in animal models,
      whereas shRNA-mediated CEACAM6 knockdown had the opposite effect. Furthermore, we
      demonstrated that miR-29a/b/c specific for CEACAM6 could regulate its expression
      at the post-transcriptional level. Collectively, our findings identified CEACAM6,
      which is regulated by miR-29a/b/c, as an important positive regulator of EMT in
      pancreatic cancer offering an explanation for how elevated levels of CEACAM6 are
      likely to contribute to the highly metastatic phenotype of pancreatic cancer.

PMID- 23857346
TI  - Differential peroxidase activities in three different crops upon insect feeding.
AB  - Peroxidases are the ubiquitous enzyme and reported to be present in all living
      genera. They catalyses reduction of peroxide and generate reactive oxygen
      species. In the present study we demonstrated that insect infestation induces
      peroxidase activity in sap and total soluble protein (TSP) of plant leaves. Three
      important crop plants viz. tomato, cowpea and cotton were used for this study.
      After infestation of chewing insect, Peroxidase activity in the sap and TSP of
      all the studied plants were enhanced in the range of 1.6 to 3.14 fold. Similar
      observations were also obtained with feeding of sap sucking insects, in which
      increment in peroxidase activity of sap and TSP was in the range of 1.8 to 2.53
      fold. Enhanced peroxidase activity was reconfirmed by in-gel peroxidase assay.
      Enzyme kinetic study showed turn over efficiency of peroxidase from cotton
      (~101.3 min(-1)) was almost similar to tomato (~100.8 min(-1)) but higher than
      cowpea (~98.21 in(-1)). MS/MS analysis of observed band showed significant
      similarity with the reported peroxidases in database.

PMID- 23857347
TI  - MIDGET cooperates with COP1 and SPA1 to repress flowering in Arabidopsis
      thaliana.
AB  - The life cycle of plants is strictly regulated by light, which directly
      influences the initiation of developmental programs such as photomorphogenesis of
      seedlings and induction of flowering. When environmental conditions are
      unsuitable, both processes are actively repressed by the action of COP1/SPA
      protein complexes which participate in ubiquitylation and subsequent degradation
      of transcription factors. We have shown recently that MIDGET (MID), a regulator
      of the TOPOISOMERASE VI complex, physically interacts with COP1 and is required
      for its function as suppressor of photomorphogenesis. Here we show that in
      Arabidopsis thaliana, the MID protein similarly plays a role in COP1/SPA1
      controlled repression of flowering under short-day conditions.

PMID- 23857348
TI  - Overexpression of AtALMT1 in the Arabidopsis thaliana ecotype Columbia results in
      enhanced Al-activated malate excretion and beneficial bacterium recruitment.
AB  - AtALMT1 (Arabidopsis thaliana ALuminum activated Malate Transporter 1) encodes an
      Arabidopsis thaliana malate transporter that has a pleiotropic role in
      Arabidopsis stress tolerance. Malate released through AtALMT1 protects the root
      tip from Al rhizotoxicity, and recruits beneficial rhizobacteria that induce
      plant immunity. To examine whether the overexpression of AtALMT1 can improve
      these traits, the gene, driven by the cauliflower mosaic virus 35S promoter, was
      introduced into the Arabidopsis ecotype Columbia. Overexpression of the gene
      enhanced both Al-activated malate excretion and the recruitment of beneficial
      bacteria Bacillus subtilis strain FB17. These findings suggest that
      overexpression of AtALMT1 can be used as an approach to enhance a plant's ability
      to release malate into the rhizosphere, which can enhance plant tolerance to some
      environmental stress factors.

PMID- 23857349
TI  - Effectors of root sedentary nematodes target diverse plant cell compartments to
      manipulate plant functions and promote infection.
AB  - Sedentary plant-parasitic nematodes maintain a biotrophic relationship with their
      hosts over a period of several weeks and induce the differentiation of root cells
      into specialized feeding cells. Nematode effectors, which are synthesized in the
      esophageal glands and injected into the plant tissue through the syringe-like
      stylet, play a central role in these processes. Previous work on nematode
      effectors has shown that the apoplasm is targeted during invasion of the host
      while the cytoplasm is targeted during the induction and the maintenance of the
      feeding site. A large number of candidate effectors potentially secreted by the
      nematode into the plant tissues to promote infection have now been identified.
      This work has shown that the targeting and the role of effectors are more complex
      than previously thought. This review will not cover the prolific recent findings
      in nematode effector function but will instead focus on recent selected examples
      that illustrate the variety of plant cell compartments that effectors are
      addressed to in order reach their plant targets. 

PMID- 23857351
TI  - UDP-sugar pyrophosphorylase controls the activity of proceeding sugar-1-kinases
      enzymes.
AB  - Plant cell wall synthesis requires a number of different nucleotide sugars which
      provide the building blocks of the different polymers. These nucleotide sugars
      are mainly provided by de novo synthesis but recycling pathways also contribute
      to the pools. The last enzyme of the recycling pathway is UDP-sugar
      pyrophosphorylase (USP), a single copy gene in Arabidopsis, of which a knockout
      is lethal for pollen development. Here we analyze the dependency between USP
      enzyme activity and the upstream glucuronokinase. Gene silencing of USP by miRNA
      cause a concomitant reduction of USP and of glucuronokinase activity presumably
      to prevent the accumulation of sugar-1-phosphates interfering with normal
      metabolism and depleting the phosphate pool of the cell. 

PMID- 23857350
TI  - Gibberellic acid in plant: still a mystery unresolved.
AB  - Gibberellic acid (GA), a plant hormone stimulating plant growth and development,
      is a tetracyclic di-terpenoid compound. GAs stimulate seed germination, trigger
      transitions from meristem to shoot growth, juvenile to adult leaf stage,
      vegetative to flowering, determines sex expression and grain development along
      with an interaction of different environmental factors viz., light, temperature
      and water. The major site of bioactive GA is stamens that influence male flower
      production and pedicel growth. However, this opens up the question of how female
      flowers regulate growth and development, since regulatory mechanisms/organs other
      than those in male flowers are mandatory. Although GAs are thought to act
      occasionally like paracrine signals do, it is still a mystery to understand the
      GA biosynthesis and its movement. It has not yet confirmed the appropriate site
      of bioactive GA in plants or which tissues targeted by bioactive GAs to initiate
      their action. Presently, it is a great challenge for scientific community to
      understand the appropriate mechanism of GA movement in plant's growth, floral
      development, sex expression, grain development and seed germination. The
      appropriate elucidation of GA transport mechanism is essential for the survival
      of plant species and successful crop production. 

PMID- 23857353
TI  - Signal integration on plant promoters: a case study in maize.
AB  - Gene promoters perceive numerous signals and integrate this information into a
      single response, the transcriptional activity of a gene. It was speculated that
      covalent modification of histones on the promoters might have an important
      function in storage and integration of signals. Using the genes for the core
      proteins of C4 metabolism in maize as a model, we associated the perception of
      specific signals with the establishment of individual histone modifications. Core
      elements of the histone code defined in these studies are conserved on all C4
      genes and on other maize genes that respond to similar stimuli. Moreover, the
      code is used in independent C4 lineages. However, our data also advise caution
      because interpretation of histone modifications might differ dependent on the
      promoter position of the modification. The model provided here constitutes a
      starting point for genome-wide decoding of stimulus-modification pairs in
      epigenetic gene regulation. 

PMID- 23857352
TI  - Cell wall integrity: targeted post-synthetic modifications to reveal its role in
      plant growth and defense against pathogens.
AB  - The plant cell wall, a dynamic network of polysaccharides and glycoproteins of
      significant compositional and structural complexity, functions in plant growth,
      development and stress responses. In recent years, the existence of plant cell
      wall integrity (CWI) maintenance mechanisms has been demonstrated, but little is
      known about the signaling pathways involved, or their components. Examination of
      key mutants has shed light on the relationships between cell wall remodeling and
      plant cell responses, indicating a central role for the regulatory network that
      monitors and controls cell wall performance and integrity. In this review, we
      present a short overview of cell wall composition and discuss post-synthetic cell
      wall modification as a valuable approach for studying CWI perception and
      signaling pathways. 

PMID- 23857355
TI  - Bactericidal effect of poly(acrylamide/itaconic acid)-silver nanoparticles
      synthesized by gamma irradiation against Pseudomonas aeruginosa.
AB  - Antimicrobial activity of silver nanoparticles is gaining importance due its
      broad spectrum of targets in cell compared to conventional antimicrobial agents.
      In this context, silver nanoparticles were synthesized by gamma irradiation
      induced reduction method of acrylamide and itaconic acid with irradiation dose up
      to 70 kGy. Silver nanoparticles were examined by Fourier-transform infrared,
      scanning electron microscopic images (SEM), and ultraviolet-visible
      spectrophotometer. The particle size was determined by X-ray diffraction,
      transmission electron microscopy (TEM), and dynamic light scattering. The
      antibacterial effect was studied by disk diffusion method against some bacterial
      pathogenic strains. Silver nanoparticles showed promising activity against
      Pseudomonas aeruginosa and slightly active against Escherichia coli, methicillin
      resistant Staphylococcus aureus, and Klebsiella pneumonia. The bactericidal
      effect of silver nanoparticles was tested against P. aeruginosa. The killing rate
      of P. aeruginosa was found to be 90 % of viability at (100 MUl/ml) of silver
      nanoparticles. Exposure of P. aeruginosa cells to silver nanoparticles caused
      fast loss of 260 nm absorbing materials and release of potassium ions. The TEM
      and SEM observation showed that silver nanoparticles may destroy the structure of
      bacterial cell membrane in order to enter the bacterial cell resulting in the
      leakage of the cytoplasmic component and the eventual death. 

PMID- 23857354
TI  - Physical exercise-induced changes in the core body temperature of mice depend
      more on ambient temperature than on exercise protocol or intensity.
AB  - The mechanisms underlying physical exercise-induced hyperthermia may be species
      specific. Therefore, the present study aimed to investigate the effects of
      exercise intensity and ambient temperature on the core body temperature (T core)
      of running mice, which provide an important experimental model for advancing the
      understanding of thermal physiology. We evaluated the influence of different
      protocols (constant- or incremental-speed exercises), treadmill speeds and
      ambient temperatures (T a) on the magnitude of exercise-induced hyperthermia. To
      measure T core, a telemetric sensor was implanted in the abdominal cavity of male
      adult Swiss mice under anesthesia. After recovering from the surgery, the animals
      were familiarized to running on a treadmill and then subjected to the different
      running protocols and speeds at two T a: 24  degrees C or 34  degrees C. All of
      the experimental trials resulted in marked increases in T core. As expected, the
      higher-temperature environment increased the magnitude of running-induced
      hyperthermia. For example, during incremental exercise at 34  degrees C, the
      maximal T core achieved was increased by 1.2  degrees C relative to the value
      reached at 24  degrees C. However, at the same T a, neither treadmill speed nor
      exercise protocol altered the magnitude of exercise-induced hyperthermia. We
      conclude that T core of running mice is influenced greatly by T a, but not by the
      exercise protocols or intensities examined in the present report. These findings
      suggest that the magnitude of hyperthermia in running mice may be regulated
      centrally, independently of exercise intensity.

PMID- 23857356
TI  - HIV and related risk behaviors among female sex workers in Iran: bias-adjusted
      estimates from the 2010 National Bio-Behavoral Survey.
AB  - In a national, facility-based survey of female sex workers in 14 cities of Iran
      (N = 872), HIV prevalence was measured at 4.5 % (95 % CI, 2.4-8.3) overall and at
      11.2 % (95 % CI, 3.4-18.9) for FSW with a history of injection drug use. Using
      methods to correct for biases in reporting sensitive information, the estimate of
      unprotected sex in last act was 35.8 %, ever injecting drugs was 37.6 %, sexually
      transmitted disease symptoms was 82.1 %, and not testing for HIV in the last year
      was 64.0 %. The amount of bias correction ranged from <1 to >30 %, in parallel
      with the level of stigma associated with each behavior. Considering the current
      upward trajectory of HIV infection in the Middle East and North Africa region, as
      well as the ongoing high level of risky behaviors and considerable underreporting
      of many such behaviors in surveys, bias corrections may be needed, especially in
      the context of Iran, to obtain more accurate information to guide prevention and
      care responses to stop the growing HIV epidemic in this vulnerable group of
      women. 

PMID- 23857357
TI  - The influence of clinical donor factors on acute rejection among lung and kidney
      recipients from the same multi-organ donor.
AB  - BACKGROUND: Acute (AR) and Chronic (CR) rejection cause considerable morbidity
      and mortality following transplantation. This study explores the associations of
      biopsy proven AR in lung (LTx) and kidney (KTx) transplants recipients from the
      one donor. MATERIAL AND METHODS: Between 2001 and 2006, 136 multiorgan donors
      contributed 144 LTx and 261 matching KTx. Utilizing LTx records and the
      Australian and New Zealand Dialysis and Transplant Registry, this study analyses
      the incidence and associations of LTx and KTx AR. RESULTS: AR was noted in 49% of
      LTx [median of 17 (11-347) days] and 29% of KTx [median of 22 (1-1044) days].
      Following univariate and multivariate analyses: 1) LTx AR was not associated with
      PGD in either LTx or KTX, nor with AR in KTx recipients, but was associated with
      donor PaO2/FiO2 ratio, type of LTx, CMV bronchoalveolar lavage load and extent of
      HLA mismatching; 2) KTx AR was not associated with PGD, but was associated with
      AR in the paired kidney, HLA DR mismatching and HLA A matching. CONCLUSIONS: AR
      in LTx and KTx recipients from the same donor are not associated. AR and PGD do
      not appear linked in either organ. KTx (and not LTx) AR was associated with CR
      related graft loss.

PMID- 23857358
TI  - Receptor-like cytoplasmic kinases are pivotal components in pattern recognition
      receptor-mediated signaling in plant immunity.
AB  - Innate immunity is generally initiated with recognition of conserved pathogen
      associated molecular patterns (PAMPs). PAMPs are perceived by pattern recognition
      receptors (PRRs), leading to activation of a series of immune responses,
      including the expression of defense genes, ROS production and activation of MAP
      kinase. Recent progress has indicated that receptor-like cytoplasmic kinases
      (RLCKs) are directly activated by ligand-activated PRRs and initiate pattern
      triggered immunity (PTI) in both Arabidopsis and rice. To suppress PTI, pathogens
      inhibit the RLCKs by many types of effectors, including AvrAC, AvrPphB and
      Xoo1488. In this review, we summarize recent advances in RLCK-mediated PTI in
      plants.

PMID- 23857359
TI  - An integrative statistical method to explore herbivory-specific responses in
      plants.
AB  - Spatial-temporal coordination between multiple processes/pathways is a key
      determinant of whole-organism transcriptome and metabolome reconfigurations in
      plants' response to biotic stresses. To explore tissue-based interdependencies in
      Nicotiana attenuata's resistance to insect attack, we performed time course
      analyses of the plant's transcriptome and metabolome in herbivory-elicited source
      leaves and unelicited sink leaves and roots. To dissect the multidimensionality
      of these responses, we have recently designed a novel approach of constructing
      interactive motifs by combining an extended self-organizing maps (SOM) based
      dimensionality reduction method with bootstrap-based non-parametric AN OVA
      models. In this previous study, we used this method to study nonlinearities in
      gene-metabolite associations involved in the acyclic diterpene glucoside pathway.
      Here, we extend the application of this method to the extraction of genes showing
      herbivory-elicitation specifically in systemic (distal from the treatment sites)
      tissues using motif analysis for different combinations of treatment applied to
      Nicotiana attenuata.

PMID- 23857360
TI  - Sl-IAA27 gene expression is induced during arbuscular mycorrhizal symbiosis in
      tomato and in Medicago truncatula.
AB  - Aux/IAA genes play a pivotal role in auxin transcriptional regulation. Their
      functions were mainly studied in Arabidopsis through analysis of gain-of-function
      mutants. In the tomato, the Solanaceae reference species, different studies on Sl
      IAA down-regulated lines showed specific role for Sl-IAA genes. Our recent work
      revealed that the Sl-IAA 27 gene displays a distinct behavior compared with most
      Aux/IAA genes, being down-regulated by auxin. Interestingly, the silencing of Sl
      IAA27 leads to altered chlorophyll accumulation in leaves, reduced fertilization,
      altered fruit development and altered root formation. Here we report that IAA27
      could be a key auxin signaling gene involved in AM in tomato and also in Medicago
      model plant. Indeed both Sl-IAA27 and its closest homolog in Medicago truncatula,
      Mt-IAA27, are overexpressed in mycorrhized roots. These data are in line with the
      putative role of auxin in arbuscular mycorrhization.

PMID- 23857361
TI  - Under-expression of the Auxin Response Factor Sl-ARF4 improves postharvest
      behavior of tomato fruits.
AB  - Auxin is one of the most prominent phytohormones regulating many aspects of
      fleshy fruit development including fruit set, fruit size through the control of
      cell division and cell expansion, and fruit ripening. To shed light on the role
      of auxin fruit ripening, we have previously shown that Sl-ARF4 is a major player
      in mediating the auxin control of sugar metabolism in tomato fruit (cv MicroTom).
      Further extending this study, we show here that down-regulation of Sl-ARF4 in
      tomato alters some ripening-related fruit quality traits including enhanced fruit
      density at mature stage, increased firmness, prolonged shelf-life and reduced
      water (weight) loss at red ripe stage. These findings suggest that Sl-ARF4 plays
      a role in determining fruit cell wall architecture and thus providing a potential
      genetic marker for improving post-harvest handling and shelf life of tomato
      fruits.

PMID- 23857362
TI  - UBIQUITIN-SPECIFIC PROTEASE16 interacts with a HEAVY METAL ASSOCIATED
      ISOPRENYLATED PLANT PROTEIN27 and modulates cadmium tolerance.
AB  - Protein ubiquitination and deubiquitination are two reversible processes
      catalyzed by ubiquitin ligases and deubiquitinating enzymes, respectively. In
      Arabidopsis, lots of substrates of ubiquitin ligases were found, whereas only a
      few targets of deubiquitinating enzymes were identified. Recently, we reported
      that a functional UBIQUITIN-SPECIFIC PROTEASE16 (UBP16) was involved in salt
      tolerance through positively regulating plasma membrane Na+/H+ antiport activity
      and at least partially modulating SERINE HYDROXYMETHYLTRANSFERASE1 (SHM 1)
      stability and activity. Here, we report that UBP16 interacts with HEAVY META L
      ASSOCIATED ISOPRENYLATED PLANT PROTEIN 27 (HI PP27), a metallochaperone
      containing a predicted heavy-metal-associated domain, which has been reported to
      play an important role in cadmium detoxification. Meanwhile, the ubp16 mutant
      showed more sensitive to cadmium than wild-type. Taken together, HI PP27 may be
      another target of UBP16 in cadmium response.

PMID- 23857363
TI  - MYC2 differentially regulates GATA-box containing promoters during seedling
      development in Arabidopsis.
AB  - MY C2 is an important transcription factor, which modulates transcription by
      directly binding to Z-, G- and E-box elements present in the promoters of light
      and different stress responsive genes. Very recently, we have shown that MY C2
      plays a role in the regulation of Z- and/or G-box containing promoters during
      both seedling and adult plant growth. Although, MY C2 does not bind to the GATA
      box light responsive element (LRE ) in vitro as shown in DNA binding assays, its
      involvement in the regulation of GATA -box containing promoter in planta, if any,
      is not known. Here, we report that the promoter activity of GATA-NOS101 in atmyc2
      mutant was found to be similar to wild-type in BL and dark grown seedlings,
      whereas it was found to be lower compared with wild-type as revealed from GUS
      staining results. Further, we will discuss the consequences of MY C2 regulating
      GATA -box containing promoter in combination with G-box containing promoters.

PMID- 23857364
TI  - Herbivory by the insect diaphorina citri induces greater change in citrus plant
      volatile profile than does infection by the bacterium, Candidatus Liberibacter
      asiaticus.
AB  - The volatile organic compound (VOC) profile in plant leaves often changes after
      biotic and abiotic stresses. Monitoring changes in VOCs in plant leaves could
      provide valuable information about multitrophic interactions. In the current
      study, we investigated the effect of Asian citrus psyllid (ACP) infestation,
      citrus greening pathogen (Candidatus Liberibacter asiaticus [CLas]) infection,
      and simultaneous attack by ACP and CLas on the VOC content of citrus leaves. Leaf
      volatiles were extracted using hexane and analyzed with gas chromatography-mass
      spectrometry (GC-MS). Although ACP is a phloem-sucking insect that causes minimal
      damage to plant tissues, the relative amount of 21 out of the 27 VOCs increased 2
      to 10-fold in ACP-infested plants. The relative amount of d-limonene, beta
      phelandrene, citronellal, and undecanal were increased 4- to 20- fold in CLas
      infected plants. A principle component analysis (PCA) and cluster analysis (CA)
      showed that VOC patterns of ACP-infested and CLas-infected plants were different
      from each other and were also different from the controls, while the VOC pattern
      of double-attacked plants was more like that of the controls than that of ACP
      infested or CLas-infected plants. VOC amounts from leaves were compromised when
      plants were attacked by ACP and CLas. The results of this study showed that a
      simple direct extraction of citrus leaf volatiles could be successfully used to
      discriminate between healthy and CLas-infected plants. Information about the
      effects of insect and pathogen attack on the VOC content profile of plants might
      contribute to a better understanding of biotic stress.

PMID- 23857365
TI  - ZIFL1.1 transporter modulates polar auxin transport by stabilizing membrane
      abundance of multiple PINs in Arabidopsis root tip.
AB  - Cell-to-cell directional flow of the phytohormone auxin is primarily established
      by polar localization of the PIN auxin transporters, a process tightly regulated
      at multiple levels by auxin itself. We recently reported that, in the context of
      strong auxin flows, activity of the vacuolar ZIFL1.1 transporter is required for
      fine-tuning of polar auxin transport rates in the Arabidopsis root. In
      particular, ZIFL1.1 function protects plasma-membrane stability of the PIN 2
      carrier in epidermal root tip cells under conditions normally triggering PIN 2
      degradation. Here, we show that ZIFL1.1 activity at the root tip also promotes
      PIN 1 plasma-membrane abundance in central cylinder cells, thus supporting the
      notion that ZIFL1.1 acts as a general positive modulator of polar auxin transport
      in roots.

PMID- 23857366
TI  - FCRL3 promotes TLR9-induced B-cell activation and suppresses plasma cell
      differentiation.
AB  - Fc receptor-like (FCRL) molecules are preferentially expressed by B lymphocytes
      and possess tyrosine-based immunoregulatory function. Although they generally
      inhibit B-cell receptor signaling, their influence on other activation pathways
      remains largely unexplored. In humans, FCRL3 encodes a type I transmembrane
      protein harboring both cytoplasmic ITAM and ITIM elements that can repress B-cell
      receptor activation. Despite this inhibitory property, mounting associations for
      FCRL3 with autoimmune and lympho-proliferative disorders imply a role for it in
      promoting B-cell pathogenesis. Here, we explore the influence of FCRL3 on B-cell
      responses to innate TLR9 stimulation. A detailed survey of blood B-cell
      populations found that FCRL3 expression increased as a function of
      differentiation and was higher among memory subsets with innate-like features.
      FCRL3 ligation augmented CpG oligodeoxynucleotide TLR9-mediated B-cell
      proliferation, activation, and survival, but surprisingly, abrogated plasma cell
      differentiation and antibody production. Although FCRL3 amplified the NF-kappaB
      and mitogen-activated protein kinase signaling cascades, it halted CpG triggered
      BLIMP1 induction in an ERK-dependent fashion. These findings indicate that FCRL3
      differentially modulates innate signaling in B cells and provide new insight into
      the potential of this disease-associated receptor to counter-regulate adaptive
      and innate immunity. 

PMID- 23857368
TI  - The time is now for gene- and genome-based bacterial diagnostics: "you say you
      want a revolution".

PMID- 23857370
TI  - A retrospective review of cytogenetic studies on methyl isocyanate with special
      reference to the Bhopal gas tragedy: is the next generation also at risk?
AB  - The world's worst industrial disaster, at Union Carbide, Bhopal, India, took
      place on 2-3 December 1984, leading to the leakage of poisonous methyl-isocyanate
      into the environment, causing thousands of deaths, pregnancy loss and for some,
      incapacitation for life. More than a quarter of a century later, the Indian
      Council of Medical Research undertook to redefine the abysmal consequences of the
      toxic gas exposure on the exposed population. This invigorated the interest of
      scientific community in the evaluation of the long-term effects, with reference
      to cytogenetic parameters. The thrust area was identified in terms of genetic
      disorders, low birth weight, developmental/growth disorders and congenital
      malformations. Also the impact on epigenetic factors, which may have contributed
      to variations in the functional expression of genes, was not negated, stimulating
      intense scientific research on in utero exposure and the progeny of the exposed
      population. To accomplish this mammoth task, molecular cytogenetic investigations
      must be undertaken in conjunction with conventional cytogenetics, using
      techniques such as FISH, Immuno-FISH, SKY and SNP analysis, to build up a
      cytogenetic database of the surviving population. 

PMID- 23857367
TI  - Autonomous vascular networks synchronize GABA neuron migration in the embryonic
      forebrain.
AB  - Gamma-aminobutyric acid neurons, born in remote germinative zones in the ventral
      forebrain (telencephalon), migrate tangentially in two spatially distinct streams
      to adopt their specific positions in the developing cortex. The cell types and
      molecular cues that regulate this divided migratory route remains to be
      elucidated. Here we show that embryonic vascular networks are strategically
      positioned to fulfil the task of providing support as well as critical guidance
      cues that regulate the divided migratory routes of gamma-aminobutyric acid
      neurons in the telencephalon. Interestingly, endothelial cells of the
      telencephalon are not homogeneous in their gene expression profiles. Endothelial
      cells of the periventricular vascular network have molecular identities distinct
      from those of the pial network. Our data suggest that periventricular endothelial
      cells have intrinsic programs that can significantly mould neuronal development
      and uncovers new insights into concepts and mechanisms of central nervous system
      angiogenesis from both developmental and disease perspectives. 

PMID- 23857371
TI  - Cadmium and hypertension in exposed workers: A meta-analysis.
AB  - OBJECTIVES: In the general population, cadmium seems to be responsible for
      hypertension, atherosclerosis and an increase in acute coronary events.
      Therefore, the purpose of this meta-analysis was to analyze controlled studies
      conducted on cadmium and arterial pressure in occupationally-exposed workers.
      MATERIALS AND METHODS: After analyzing all the relevant articles found in the
      literature, 6 publications were selected. RESULTS: A higher prevalence of
      hypertension and higher values of systolic and diastolic blood pressure were
      recorded in the exposed subjects. CONCLUSIONS: Cadmium in occupationally-exposed
      individuals appears to induce an increase in systolic and diastolic blood
      pressure and an increase in the prevalence of hypertension.

PMID- 23857372
TI  - Job stress and mortality in older age.
AB  - OBJECTIVES: This paper aims to assess the relationship between the determinants
      of the psychosocial work environment, as expressed in terms of JDC or ERI models,
      and all-cause mortality in older individuals. MATERIALS AND METHODS: The baseline
      study was conducted on a cohort comprising a random sample of 65-year-old
      community-dwelling citizens of Krakow, Poland. All of the 727 participants (410
      women, 317 men) were interviewed in their households in the period between 2001
      and 2003; a structured questionnaire was used regarding their occupational
      activity history, which included indexes measuring particular dimensions of their
      psychosocial work environment based on Karasek's Job Demand-Control model and
      Siegrist's Effort-Reward Imbalance model, as well as health-related quality of
      life and demographic data. Mortality was ascertained by monitoring City Vital
      Records for 7 years. Analyses were conducted separately for men and women, with
      the multivariate Cox proportional hazard model. RESULTS: During a 7-year follow
      up period, 59 participants (8.1%) died, including 21 women (5.1% of total women)
      and 38 men (12%) (p < 0.05). Significant differences in the number of deaths
      occurred regarding disproportion between physical demands and control in men:
      those with low physical demands and low control died three times more often than
      those with high control, regardless of the level of demands. The multivariate Cox
      proportional hazard model showed that significantly higher risk of death was
      observed only in men with low physical demands and low control, compared to those
      with low physical demands and high control (Exp(B) = 4.65, 95% CI: 1.64-13.2).
      CONCLUSIONS: Observed differences in mortality patterns are similar to the
      patterns of relationships observed in health-related quality of life (HRQoL)
      level at the beginning of old age; however, the relationship between efforts and
      rewards or demands and control and mortality was not fully confirmed.

PMID- 23857373
TI  - The use of protective gloves by medical personnel.
AB  - INTRODUCTION: To minimize the risk of cross-infection between the patient and the
      medical staff, it is necessary to use individual protective measures such as
      gloves. According to the recommendations of the Centers for Disease Control and
      Prevention (CDC) and the World Health Organization (WHO), protective gloves
      should always be used upon contact with blood, mucosa, injured skin or other
      potentially infectious material. MATERIALS AND METHODS: The aim of the study was
      to evaluate, through quasi-observation, the use of protective gloves by medical
      staff according to the guidelines issued by the CDC and WHO. The results were
      subject to statistical analysis (p < 0.05). RESULTS: During 1544 hours of
      observations, 3498 situations were recorded in which wearing protective gloves is
      demanded from the medical staff. The overall percentage of the observance of
      using gloves was 50%. The use of gloves depended significantly on the type of
      ward, profession, performed activity, number of situations that require wearing
      gloves during the observation unit and the real workload. During the entire
      study, as many as 718 contacts with patients were observed in which the same
      gloves were used several times. CONCLUSION: Wearing disposable protective gloves
      by the medical staff is insufficient.

PMID- 23857374
TI  - The human impact of volcanoes: a historical review of events 1900-2009 and
      systematic literature review.
AB  - Introduction. More than 500 million people live within the potential exposure
      range of a volcano. The risk of catastrophic losses in future eruptions is
      significant given population growth, proximities of major cities to volcanoes,
      and the possibility of larger eruptions. The objectives of this review are to
      describe the impact of volcanoes on the human population, in terms of mortality,
      injury, and displacement and, to the extent possible, identify risk factors
      associated with these outcomes. This is one of five reviews on the human impact
      of natural disasters. Methods. Data on the impact of volcanoes were compiled
      using two methods, a historical review of volcano events from 1900 to 2009 from
      multiple databases and a systematic literature review of publications ending in
      October 2012. Analysis included descriptive statistics and bivariate tests for
      associations between volcano mortality and characteristics using STATA 11.
      Findings. There were a total of 91,789 deaths (range: 81,703-102,372), 14,068
      injuries (range 11,541-17,922), and 4.72 million people affected by volcanic
      events between 1900 and 2008. Inconsistent reporting suggests this is an
      underestimate, particularly in terms of numbers injured and affected. The primary
      causes of mortality in recent volcanic eruptions were ash asphyxiation, thermal
      injuries from pyroclastic flow, and trauma. Mortality was concentrated with the
      ten deadliest eruptions accounting for more than 80% of deaths; 84% of fatalities
      occurred in four locations (the Island of Martinique (France), Colombia,
      Indonesia, and Guatemala). Conclusions. Changes in land use practices and
      population growth provide a background for increasing risk; in conjunction with
      increasing urbanization in at risk areas, this poses a challenge for future
      volcano preparedness and mitigation efforts. 

PMID- 23857376
TI  - Capillary electrophoresis coupled to evaporative light scattering detection for
      direct determination of underivatized amino acids: application to tea samples
      using carboxyled single-walled carbon nanotubes for sample preparation.
AB  - An improved and efficient method for the determination of underivatized amino
      acids based on the use of CE coupled to evaporative light scattering detector
      (ELSD), involving carbon nanotubes, was successfully developed. Carboxyled single
      walled carbon nanotubes were used for the first time to perform the clean-up of
      the analyzed samples, which were afterwards analyzed by CE-ELSD. White tea
      samples were used to demonstrate the usefulness of the CE-ELSD coupled
      methodology. A suitable interface, based on a triple tube design sprayer, was
      developed and successfully used for coupling both instruments. Parameters
      affecting the separation and determination, including the elimination of
      interferences, were studied and properly optimized. Under the optimized
      conditions good resolution was achieved for the separation of seven amino acids.
      The precision of the method, expressed as RSD, was found within the 3.5-5.3%
      range. The LOD obtained for the proposed method were in the 1.2-2.1 pg range and
      the LOQ, were in the 2.0-11.5 pg range, with injection pressure of 5 KPa for 20 s
      (15.3 nL). This method is simple, rapid, and selective compared with other
      conventional techniques. 

PMID- 23857377
TI  - Microbial community assembly and succession on lake sturgeon egg surfaces as a
      function of simulated spawning stream flow rate.
AB  - We investigated microbial succession on lake sturgeon (Acipenser fulvescens) egg
      surfaces over the course of their incubation period as a function of simulated
      stream flow rate. The primary objective was to characterize the microbial
      community assembly during succession and to examine how simulated stream flow
      rate affect the successional process. Sturgeon eggs were reared under three flow
      regimes; high (0.55 m/s), low (0.18 m/s), and variable (0.35 and 0.11 m/s
      alternating 12 h intervals). Eggs were collected from each flow regime at
      different egg developmental stages. Microbial community DNA was extracted from
      egg surface and the communities were examined using 16S rRNA gene-based terminal
      restriction fragment length polymorphism and 454 pyrosequencing. Analysis of
      these datasets using principal component analysis revealed that microbial
      communities were clustered by egg developmental stages (early, middle, and late)
      regardless of flow regimes. 454 pyrosequencing data suggested that 90-98 % of the
      microbial communities were composed of the phyla Proteobacteria and Bacteroidetes
      throughout succession. beta-Protebacteria was more dominant in the early stage,
      Bacteroidetes became more dominant in the middle stage, and alpha-Proteobacteria
      became dominant in the late stage. A total of 360 genera and 5,826 OTUs at 97 %
      similarity cutoff were associated with the eggs. Midway through egg development,
      the egg-associated communities of the low flow regime had a higher diversity than
      those communities developed under high or variable flow regimes. Results show
      that microbial community turnover occurred during embryogenesis, and stream flow
      rate influenced the microbial succession processes on the sturgeon egg surfaces.

PMID- 23857378
TI  - Desert gerbils affect bacterial composition of soil.
AB  - Rodents affect soil microbial communities by burrow architecture, diet
      composition, and foraging behavior. We examined the effect of desert rodents on
      nitrogen-fixing bacteria (NFB) communities by identifying bacteria colony-forming
      units (CFU) and measuring nitrogen fixation rates (ARA), denitrification (DA),
      and CO2 emission in soil from burrows of three gerbil species differing in diets.
      Psammomys obesus is folivorous, Meriones crassus is omnivorous, consuming green
      vegetation and seeds, and Dipodillus dasyurus is predominantly granivorous. We
      also identified NFB in the digestive tract of each rodent species and in Atriplex
      halimus and Anabasis articulata, dominant plants at the study site. ARA rates of
      soil from burrows of the rodent species were similar, and substantially lower
      than control soil, but rates of DA and CO2 emission differed significantly among
      burrows. Highest rates of DA and CO2 emission were measured in D. dasyurus
      burrows and lowest in P. obesus. CFU differed among bacteria isolates, which
      reflected dietary selection. Strains of cellulolytic representatives of the
      family Myxococcaceae and the genus Cytophaga dominated burrows of P. obesus,
      while enteric Bacteroides dominated burrows of D. dasyurus. Burrows of M. crassus
      contained both cellulolytic and enteric bacteria. Using discriminant function
      analysis, differences were revealed among burrow soils of all rodent species and
      control soil, and the two axes accounted for 91 % of the variance in bacterial
      occurrences. Differences in digestive tract bacterial occurrences were found
      among these rodent species. Bacterial colonies in P. obesus and M. crassus
      burrows were related to bacteria of A. articulata, the main plant consumed by
      both species. In contrast, bacteria colonies in the burrow soil of D. dasyurus
      were related to bacteria in its digestive tract. We concluded that gerbils play
      an important role as ecosystem engineers within their burrow environment and
      affect the microbial complex of the nitrogen-fixing organisms in soils. 

PMID- 23857379
TI  - Effects of cobalt on membrane ATPases, oxidant, and antioxidant values in the
      cerebrum and cerebellum of suckling rats.
AB  - Chronic overexposure to cobalt (Co) may result in neurotoxic effects, but the
      mechanism of Co-induced neurotoxicity is not yet well established. Our study was
      conducted to determine whether Co is associated to the induction of central
      nervous system damage in pregnant rats and their progeny. Twelve pregnant female
      rats were randomly divided into 2 groups: group I served as controls and group II
      received Co (350 mg/L, orally). Treatments started from the 14th day of pregnancy
      until day 14 after delivery. Co concentration in plasma was higher in the treated
      groups than in the controls. Exposure to Co also increased the levels of MDA,
      PCO, H2O2, and AOPP, while Na(+)K(+)-ATPase and Mg(2+)-ATPase, AChE, and BuChE
      activities decreased in the cerebrum and cerebellum of suckling pups. A smear
      without ladder formation on agarose gel was also shown in the cerebrum and
      cerebellum, indicating random DNA degradation. A reduction in GPx, SOD, CAT, GSH,
      NPSH, and vitamin C values was observed. The changes were confirmed by
      histological results. In conclusion, these data showed that the exposure of
      pregnant and lactating rats to Co resulted in the development of oxidative stress
      and the impairment of defense systems in the cerebrum and cerebellum of their
      suckling pups.

PMID- 23857380
TI  - Na+/I- symporter and type 3 iodothyronine deiodinase gene expression in amniotic
      membrane and placenta and its relationship to maternal thyroid hormones.
AB  - Placental type 3 iodothyronine deiodinase (D3) potentially protects the fetus
      from the elevated maternal thyroid hormones. Na(+)/I(-) symporter (NIS) is a
      plasma membrane glycoprotein, which mediates active iodide uptake. Our objectives
      were to establish the distribution of NIS and D3 gene expressions in the placenta
      and the amniotic membrane and to investigate the relationship between placental
      D3 and NIS gene expressions and maternal iodine, selenium, and thyroid hormone
      status. Thyroid hormones, urinary iodine concentration (UIC), and selenium levels
      were measured in 49 healthy term pregnant women. NIS and D3 gene expressions were
      studied with the total mRNA RT-PCR method in tissues from maternal placenta (n =
      49), fetal placenta (n = 9), and amniotic membrane (n = 9). NIS and D3 gene
      expressions were shown in the fetal and maternal sides of the placenta and
      amniotic membrane. Mean blood selenium level was 66 +/- 26.5 MUg/l, and median
      UIC was 143 MUg/l. We could not demonstrate any statistically significant
      relationship of spot UIC and blood selenium with NIS and D3 expression (p >
      0.05). Positive correlations were found between NIS and thyroxine-binding
      globulin (TBG) (r = 0.3, p = 0.042) and between D3 and preoperative glucose
      levels (r = 0.4, p = 0.006). D3 and NIS genes are expressed in term placenta and
      amniotic membrane; thus, in addition to placenta, amniotic membrane contributes
      to regulation of maternofetal iodine and thyroid hormone transmission. Further
      studies are needed to clarify the relationship between maternal glucose levels
      and placental D3 expression and between TBG and placental NIS expression.

PMID- 23857382
TI  - Budd-chiari syndrome management: Timing of treatment is an open issue.

PMID- 23857381
TI  - Differential epigenome-wide DNA methylation patterns in childhood obesity
      associated asthma.
AB  - While DNA methylation plays a role in T-helper (Th) cell maturation, its
      potential dysregulation in the non-atopic Th1-polarized systemic inflammation
      observed in obesity-associated asthma is unknown. We studied DNA methylation
      epigenome-wide in peripheral blood mononuclear cells (PBMCs) from 8 obese
      asthmatic pre-adolescent children and compared it to methylation in PBMCs from 8
      children with asthma alone, obesity alone and healthy controls. Differentially
      methylated loci implicated certain biologically relevant molecules and pathways.
      PBMCs from obese asthmatic children had distinctive DNA methylation patterns,
      with decreased promoter methylation of CCL5, IL2RA and TBX21, genes encoding
      proteins linked with Th1 polarization, and increased promoter methylation of
      FCER2, a low-affinity receptor for IgE, and of TGFB1, inhibitor of Th cell
      activation. T-cell signaling and macrophage activation were the two primary
      pathways that were selectively hypomethylated in obese asthmatics. These findings
      suggest that dysregulated DNA methylation is associated with non-atopic
      inflammation observed in pediatric obesity-associated asthma. 

PMID- 23857383
TI  - Pandemic Influenza A(H1N1) in Cote d'Ivoire: health-care providers' knowledge of
      influenza and attitudes towards vaccination.
AB  - INTRODUCTION: During the 2009 influenza A(H1N1) pandemic (pH1N1), different
      methods were promoted to reduce the spread of influenza, including respiratory
      etiquette and vaccination. To identify knowledge gaps about influenza and to plan
      the vaccination campaign against the pandemic in Cote d'Ivoire, a survey was
      conducted among health-care providers (HCPs) to assess their knowledge about
      influenza and their willingness to be vaccinated. METHODOLOGY: A cross-sectional
      survey was performed in the city of Abidjan on 16-18 February 2010, in the three
      university teaching hospitals, a randomly selected general hospital, and two
      randomly selected private clinics. In face-to-face interviews, 383 health-care
      professionals were asked questions about their knowledge of influenza, means of
      influenza prevention, and their willingness to be vaccinated. Data analysis, both
      univariate and multivariate, was performed using SPSS. RESULTS: Willingness to be
      vaccinated against pH1N1 was 80% (n = 284), and 83% of the HCPs would recommend
      the vaccine to others. The respiratory mode of transmission of influenza was
      known by 85% (n = 295) of the participants and 50% (n = 174) believed that
      seasonal influenza virus and pH1N1 virus were different. In a multivariate model,
      the factors significantly associated with willingness to receive pH1N1vaccine
      were fear of pH1N1 disease (OR = 2.1; IC = 1.02-4.35), having only a high school
      education (OR = 8.28; IC = 2.04-33.60), and feeling at risk to contract pH1N1 (OR
      = 11.43; IC = 4.77-27.38). CONCLUSION: The willingness to be vaccinated against
      influenza A (H1N1) by health professionals is real.

PMID- 23857384
TI  - Risk factors for bacteremia due to extended-spectrum beta-lactamase-producing
      Escherichia coli in a Turkish hospital.
AB  - INTRODUCTION: Bloodstream infection caused by extended-spectrum beta-lactamase
      (ESBL)-producing pathogens has become a serious concern worldwide. The purpose of
      this study was to identify risk factors for bacteremia due to ESBL-producing
      Escherichia coli in a Turkish hospital. METHODOLOGY: We retrospectively reviewed
      the medical records of patients with E. coli bacteremia in a tertiary care centre
      from January 2007 to October 2011. Data from patients such as demographic
      features, underlying conditions, and antibiotic exposure were analysed. RESULTS:
      A total of 113 patients with bacteremia due to E. coli were included and data
      from patients with ESBL-producing E. coli (case patients) were compared to those
      with non-ESBL-producing E. coli (control patients). The frequency of ESBL
      producers was 38.9% (44/113). Exposure to fluoroquinolones and cephalosporins,
      history of intra-abdominal surgery intervention, and presence of central venous
      catheteter and urinary catheteter were more frequently detected among case
      patients (P < 0.05). Independent risk factors for bacteremia due to ESBL
      producing E. coli were exposure to fluoroquinolones (OR 13.39, 95% CI 1.28
      140.03) and cephalosporins (OR 3.48, 95% CI 1.03-11.74). CONCLUSIONS: Previous
      use of fluoroquinolone and cephalosporin in patients with bacteremia caused by E.
      coli increased the risk for ESBL-producing strains.

PMID- 23857385
TI  - Antibiogram and characterization of resistance markers among Escherichia coli
      Isolates from urinary tract infections.
AB  - INTRODUCTION: Urinary tract infection is the most frequently diagnosed kidney and
      urologic disease, and Escherichia coli is by far its most common etiological
      agent. Uropathogenic E. coli are responsible for approximately 90% of urinary
      tract infections seen in individuals with ordinary anatomy therefore, it is
      essential to review the antibiogram of uropathogenic E. coli periodically to help
      clinicians decide on the appropriate therapy. METHODOLOGY: We evaluated E. coli
      isolated from urinary tract infections at the National Salmonella and Escherichia
      Centre for antibiogram, plasmid transferability and stability of resistance
      markers. RESULTS: In total, 90.9% of the isolates were found to be sensitive to
      nitrofurantoin while the highest proportion of the isolates was found to be
      resistant to nalidixic acid. Minimum inhibitory concentrations of all
      antimicrobials for different isolates were well within the limits specified by
      the Clinical and Laboratory Standards Institute.  Resistance against tetracycline
      was not transferred either by conjugation and transformation. Streptomycin
      resistance was found to be lost in the maximum number of tested isolates showing
      loss at the 10th, 15th and 20th passages. CONCLUSION: Changing trends in
      antibiotic resistance necessitates the periodic generation of antibiogram data to
      help health authorities revise treatment strategies for urinary tract infections
      caused by E. coli.

PMID- 23857386
TI  - Targeting of putative fimbrial gene for detection of S. Typhi in typhoid fever
      and chronic typhoid carriers by nested PCR.
AB  - INTRODUCTION: It is important to identify Salmonella Typhi infection quickly to
      treat acute fever patients and to prevent transmission by chronic typhoid
      carriers; therefore, a very specific and sensitive diagnostic technique is highly
      desirable, especially in endemic areas. The objective of this study was to
      develop a PCR protocol targeting the putative fimbrial staA gene of S. Typhi.
      This is a preferred target gene that is specifically amplified in the S. Typhi
      serotype compared to the commonly targeted fliC gene which may also be amplified
      from the non-typhoidal Salmonella Munchen serotype. METHODOLOGY: A new nested PCR
      primer methodology was designed to target the staA gene, which is a member of the
      fimbrial gene family specific to Salmonella Typhi only. RESULTS: The primers were
      found to be very specific as the desired amplicon (377 bp) could be generated
      exclusively from S. Typhi strains including the reference strain (MTCC 3216) and
      78 clinical isolates . Restriction digestion with HinfI confirmed the identity of
      the amplified DNA fragment in clinical specimens of S. Typhi origin. 
      Furthermore, these primers were able to detect a minimum of three colony forming
      units per ml (1fg) in spiked blood samples. The detection sensitivity of the
      described primers is comparable to that of previously published primers targeting
      fliC gene sequences. CONCLUSIONS: This study indicates that the primers targeting
      the putative fimbrial staA gene are very specific to the Typhi serotype and may
      be a better alternative to fliC targeted amplification based diagnosis.

PMID- 23857387
TI  - Sodium chloride 0.9% versus Lactated Ringer in the management of severely
      dehydrated patients with choleriform diarrhoea.
AB  - INTRODUCTION: Although experience within Peru suggests clinical and physiological
      benefits of treating dehydration caused by diarrhoea with Lactated Ringer's
      solution (LR) over sodium chloride 0.9%, (NaCl) there is little documented
      scientific evidence supporting this view. It is important to clarify this issue
      and determine the best solution for use during epidemics. METHODOLOGY: Forty
      patients suffering from dehydration due to choleriform diarrhoea were enrolled in
      the study. Twenty patients were treated using NaCl (Group A) and the other twenty
      with LR (Group B). After diuresis recovery was achieved, the patients were
      continued on a course of oral rehydration salts. Serum electrolytes, arterial pH,
      HCO3-, and pCO2 were measured at three stages: at admission, after diuresis
      recovery, and after 12 hours. RESULTS: Acidosis was corrected more quickly with
      LR that NaCl. The hyperosmolality and hypernatremic states were corrected with
      both solutions. CONCLUSION: LR use resulted in a better clinical response than
      NaCl, illustrated by more rapid physiological correction, showing that mixed
      metabolic acidosis was corrected more quickly and more appropriately with this
      treatment.

PMID- 23857388
TI  - Seasonality, clinical types and prognostic factors of Vibrio vulnificus
      infection.
AB  - INTRODUCTION: Vibrio vulnificus infection, an uncommon but life-threatening
      illness, manifests as two main types, primary septicemia and primary wound
      infections.  Little information regarding the seasonality of V. vulnificus
      infections in tropical areas and prognostic factors of primary V. vulnificus
      wound infections is available. METHODOLOGY: This retrospective study was
      conducted to include 159 V. vulnificus-infected admissions at our institution in
      southern Taiwan, 63 with primary septicemia (Group 1) and 96 with primary wound
      infections (Group 2), from 1999 to 2008, for analysis. RESULTS: The case-fatality
      rate was 24%. Eighty-eight percent of these cases occurred during April to
      November. During December to March, patients in Group 2 were less likely to have
      acquired the infection compared with those in Group 1. Group 1 was more likely to
      have comorbidities and a higher case-fatality rate compared to Group 2. In
      multivariate analysis, hemorrhagic bullous skin lesions/necrotizing fasciitis
      (P=0.024), lesions involving two or more limbs (P=0.043), and shock on admission
      (P=0.015) were related to an increased mortality risk, while surgery < 24 hours
      after admission (P=0.001) was related to a decreased mortality risk in Group 1;
      however, hemorrhagic bullous skin lesions/necrotizing fasciitis (P=0.045) was the
      only prognostic factor in Group 2. CONCLUSION: The presence of hemorrhagic
      bullous lesion/necrotizing fasciitis is the main prognostic factor for primary
      septicemia or primary wound infections caused by V. vulnificus. Persons with an
      underlying immunocompromised status should avoid consuming raw/undercooked
      seafood or exposing wounds to seawater and should wear clothing during handling
      of seafood/fishing, especially in warmer months.

PMID- 23857389
TI  - Chronic hepatitis B prognostic markers other than pre-treatment viral load
      predicted composite treatment outcome.
AB  - INTRODUCTION: Chronic hepatitis B (CHB) is a globally common infectious disease.
      Its clinical course is complicated. In Southeast Asia, nucleos(t)ide analogues
      (NA) are commonly used drugs for CHB treatment. Composite treatment outcome has
      often been used in CHB clinical practice, but rarely predicted epidemiologically.
      This study aimed to compare the composite treatment outcome between CHB patients
      with low and high treatment-naive viral load, and to identify its predictors
      METHODOLOGY: This retrospective cohort study followed up 95 CHB patients on NA
      treatment for a year. Composite treatment outcome was defined as undetectable HBV
      DNA level, ALT normalization and, HBeAg clearance in the case of HBeAg-positive
      patients. Multinomial logistic regression analysis was applied to analyze the
      significant treatment response predictors. RESULTS: Complete composite treatment
      outcome was achieved by 52% of CHB patients with an initial viral load < 6.5 log
      10 copies /ml, but 31% of those had an initial viral load >= log 6.5 log 10
      copies /ml. Outcome was predicted by HBeAg negativity (adjusted relative risk
      ratio, aRRR = 11.1, 95 % confidence interval, CI 3-41.3) and ALT normalization
      within the sixth month of therapy (aRRR = 6.7, CI 1.8-24.9). An elevation of ALT
      to more than 1.5 times the normal value (40 IU/ml) can lead to an incomplete
      response on NA therapy (aRRR = 6.2, CI 1.5-26.6.) CONCLUSION: Routine clinical
      markers other than pre-treatment viral load predicted composite CHB outcome on NA
      Therapy.

PMID- 23857390
TI  - Intestinal parasitic infection among the HIV-infected patients in Nepal.
AB  - INTRODUCTION: Intestinal parasitic infection has been a significant problem in
      HIV patients, worldwide. In this study, we aimed to measure the prevalence and
      identify the factors associated with intestinal parasitic infection in people
      infected with HIV and attending National Public Health Laboratory in Kathmandu,
      Nepal, for CD4 T-cell count. METHODOLOGY: An analytical cross-sectional study in
      745 HIV-infected people attending for CD4 T-cell count was conducted. RESULTS:
      The prevalence of intestinal parasitic infection was 22.4% (95% CI 19.5 to 25.5).
      In univariate analysis, age, sex, longer time since diagnosis of HIV, CD4 T-cell
      count of <200/uL, diarrhoea, marital status, and being under tuberculosis (TB)
      treatment were significantly associated with increased odds of intestinal
      parasite infection. However, in the logistic regression model, only the CD4 T
      cell count of <200/uL (adjusted OR=4.2, 95% CI 2.5 to 7.0), diarrhoea (adjusted
      OR=2.8, 95% CI 1.8 to 4.3) and being under TB treatment (adjusted OR=2.9, 95% CI
      1.8 to 4.6) remained as significant predictors. On stratification, CD4 T-cell
      count of <200/ uL was independently associated with higher odds of protozoal as
      well as helminthes infection. The parasites Cryptosporidium and Cyclospora were
      observed only in participants with CD4 T-cell counts <200/uL. CONCLUSIONS: Both
      protozoal and helminthic intestinal parasitic infections are common in HIV
      infected people seeking care in healthcare facilities. The poor immune status as
      indicated by low CD4 T-cell count and TB may account for such a high risk of
      parasitic infection.

PMID- 23857391
TI  - The icaA gene in staphylococci from bovine mastitis.
AB  - INTRODUCTION: Staphylococcus aureus and coagulase-negative staphylococci (CNS)
      are frequently isolated from cows with mastitis. A main virulence factor of CNS
      is the ability to adhere and form biofilms. The intercellular gene cluster
      adhesion (ica) operon is one factor involved in biofilm production although ica
      independent factors are also involved. Previous reports based on the results of
      S. epidermidis and S. aureus suggested that ica is highly conserved between
      species, but this detection decreases in other CNS biofilm producers. In this
      study we evaluated the presence of the icaA gene in strains of Staphylococcus
      spp. isolated from the milk of bovines with mastitis. METHODOLOGY: Thirty-seven
      staphylococci strains were evaluated by detecting the icaA gene. A new set of PCR
      primers was designed by consensus region of eight staphylococci from GenBank.
      Species characterization was performed using the Kloos and Schleifer scheme.
      RESULTS: We identified the presence of the gene in S. aureus (n:4), S.
      chromogenes (n:4), and S. sciuri strains (n:2). We also, identified the presence
      of the gene in S. xylosus (n:5) for the first time. The icaA gene was not
      detected in S. capitis (n:1), S. epidermidis (n:2), S. hominis (n:2), S.
      saccharolyticus (n:1), S. simulans (n:4) and S. saprophyticus (n:3). The icaA
      gene was detected in 40.54% (15/37) of the CNS evaluated. CONCLUSIONS: Our
      results confirm the presence of the ica operon in various species of CNS pointing
      to polysaccharide intercellular adhesin (PIA) as the most important component for
      the formation of biofilms.

PMID- 23857392
TI  - Plasted abdominal tuberculosis presenting as an obstruction.

PMID- 23857393
TI  - First report of antibodies to Neospora caninum in Nigerian cattle.

PMID- 23857394
TI  - Insights into the ultrastructural morphology of novel Planctomycetes.
AB  - Knowledge of the interesting phylum of Planctomycetes has increased in the last
      decades both due to cultural and molecular methods. Although a restricted number
      of species have been described to date, this group presents a much larger
      diversity that has been mainly revealed by molecular ecology studies. Isolation
      experiments allowed us to get a number of new Planctomycetes taxa that extend the
      already described ones. In this work we present the ultrastructural morphological
      characterization of these new taxa as well as we give new details of Aquisphaera
      giovannonii ultrastructure. Furthermore, our interpretation on Planctomycetes
      cell envelope is provided. 

PMID- 23857395
TI  - Ectomycorrhizal inoculum potential of northeastern US forest soils for American
      chestnut restoration: results from field and laboratory bioassays.
AB  - American chestnut (Castanea dentata) was once a dominant overstory tree in
      eastern USA but was decimated by chestnut blight (Cryphonectria parasitica).
      Blight-resistant chestnut is being developed as part of a concerted restoration
      effort to bring this heritage tree back. Here, we evaluate the potential of field
      soils in the northern portion of the chestnut's former range to provide
      ectomycorrhizal (EM) fungus inoculum for American chestnut. In our first study,
      chestnut seedlings were grown in a growth chamber using soil collected from three
      sites dominated by red oak (Quercus rubra) as inoculum and harvested after 5
      months. Of the 14 EM fungi recovered on these seedlings, four species dominated
      in soils from all three sites: Laccaria laccata, a Tuber sp., Cenococcum
      geophilum, and a thelephoroid type. Seedlings grown in the nonsterilized soils
      were smaller than those growing in sterilized soils. In the second study,
      chestnut seedlings were grown from seed planted directly into soils at the same
      three sites. Seedlings with intermingling roots of established trees of various
      species were harvested after 5 months. Seventy-one EM fungi were found on the
      root tips of the hosts, with 38 occurring on chestnut seedlings. Multiple versus
      single host EM fungi were significantly more abundant and frequently encountered.
      The fungi observed dominating on seedlings in the laboratory bioassay were not
      frequently encountered in the field bioassay, suggesting that they may not have
      been active in mycelial networks in the field setting but were in the soils as
      resistant propagules that became active in the bioassay. These results show that
      soil from red oak stands can be used to inoculate American chestnut with locally
      adapted ectomycorrhizal fungi prior to outplanting, a relatively cost effective
      approach for restoration efforts. 

PMID- 23857397
TI  - Are the reported clinical outcomes with stereotactic ablative radiotherapy
      generalizable?

PMID- 23857398
TI  - Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant
      bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers.
AB  - INTRODUCTION: Bevacizumab improves survival in patients with advanced non-small
      cell lung cancer (NSCLC). This phase II clinical trial assessed the effects of
      the addition of bevacizumab to neoadjuvant chemotherapy in resectable nonsquamous
      NSCLC. METHODS: Patients with resectable stage IB-IIIA nonsquamous NSCLC were
      treated with bevacizumab followed by imaging 2 weeks later to assess single-agent
      effect. After this they received two cycles of bevacizumab with four cycles of
      cisplatin and docetaxel followed by surgical resection. Resected patients were
      eligible for adjuvant bevacizumab. The primary endpoint was the rate of
      pathological downstaging (decrease from pretreatment clinical stage to post
      treatment pathological stage). Secondary endpoints included overall survival,
      safety, and radiologic response. RESULTS: Fifty patients were enrolled. Thirty
      four (68%) were clinical stage IIIA. All three doses of neoadjuvant bevacizumab
      were delivered to 40 of 50 patients. Six patients (12%) discontinued because of
      bevacizumab-related adverse events. The rate of downstaging (38%), response to
      chemotherapy (45%), and perioperative complications (12%) were comparable with
      historical data. No partial responses were observed to single-agent bevacizumab,
      but 18% of the patients developed new intratumoral cavitation, with a trend
      toward improved pathologic response (57% versus 21%; p = 0.07). A major
      pathologic response (>=90% treatment effect) was associated with survival at 3
      years (100% versus 49%; p = 0.01). No patients with KRAS-mutant NSCLC (0 of 10)
      had a pathologic response as compared with 11 of 31 with wild-type KRAS.
      CONCLUSION: Although preoperative bevacizumab plus chemotherapy was feasible, it
      did not improve downstaging in unselected patients. New cavitation after single
      agent bevacizumab is a potential biomarker. Alternative strategies are needed for
      KRAS-mutant tumors.

PMID- 23857399
TI  - A phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in
      pretreated patients with small-cell lung cancer.
AB  - BACKGROUND: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase
      inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer
      (SCLC) with regression of tumors. METHODS: This multicenter, nonrandomized phase
      2 trial was designed to evaluate antitumor activity of LBH589 in patients with
      previously treated SCLC. Patients received LBH589 administered intravenously at a
      dose of 20 mg/mq (days 1-8) every 21 days. RESULTS: A total of 21 patients with
      extensive- or limited-stage SCLC were enrolled. Patients received a median of two
      cycles (range, 1-6). LBH589 was well tolerated, and the most common toxicities
      were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting
      19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for
      efficacy, two cases showed shrinkages more than 30% at first assessment, with
      time to progression of 14 and 21 weeks, respectively, and there were three long
      disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed
      because of a lack of activity. CONCLUSION: This is the first report of a pan
      deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in
      SCLC. We believe that although the trial was prematurely discontinued, modest
      clinical activity of LBH589 combined with a favorable safety profile in
      pretreated SCLC patients was observed, which warrants further exploration of the
      potential contribution of LBH589 in other trials.

PMID- 23857400
TI  - Brief report on the use of radiolabeled somatostatin analogs for the diagnosis
      and treatment of metastatic small-cell lung cancer patients.
AB  - INTRODUCTION: The demonstration of type 2 somatostatin receptors (SSTRs) in small
      cell lung cancer (SCLC) represents the rationale for the use of positron emission
      tomography/computed tomography (PET/CT) to determine SSTR expression, and select
      patients suitable for peptide radioreceptor radionuclide therapy (PRRT) in
      extensive-disease stage (ED) SCLC. METHODS: We evaluated 24 ED-SCLC patients with
      radiolabeled SST-analog PET/CT. Lesions at PET/CT scan were semiquantitatively
      scored (from 0 to 3+) and compared with contrast-enhanced CT findings. Patients
      scored as 3+ were admitted to PRRT after dosimetric evaluation. Average injected
      activity/cycle was 2.6 GBq (yttrium-PRRT) or 6.0 GBq (lutetium-PRRT). PRRT
      efficacy was clinically and radiologically assessed. RESULTS: PET/CT was negative
      in four of 24 patients, whereas in the remaining 20 cases uptake was scored as 1+
      in seven of 20, 2+ in one of 20, and 3+ in 12 of 20. Primary tumor lesions showed
      uptake in 16 of 24 patients. Uptake in metastatic lesions was observed in four of
      four adrenals, two of five brain, 12 of 16 bone, three of eight liver, and 17 of
      20 lymph node lesions. Of the 12 patients eligible for PRRT, 11 were eventually
      treated and four of 11 patients received multiple PRRT administrations. Dosimetry
      resulted in a BED for kidney of 7.5 Gy (range, 4-21); bone marrow provisional
      dosage was 0.43 Gy (range, 0.1-1.7). Hematological PRRT toxicity occurred in
      three of 11 patients. No clinical or objective responses were observed with
      disease progression occurring approximately 48 days (range, 9-32) after PRRT.
      CONCLUSION: Radiolabeled SST-analog PET/CT demonstrated enhanced SSTR expression
      in 50% of cases. Nevertheless, PRRT in ED-SCLC was ineffective, suggesting the
      need to anticipate or combine PRRT in a multimodality approach.

PMID- 23857402
TI  - Giant malignant granular cell tumor (GCT) of the posterior mediastinum.

PMID- 23857401
TI  - EZH2 promotes E2F-driven SCLC tumorigenesis through modulation of apoptosis and
      cell-cycle regulation.
AB  - INTRODUCTION: Although enhancer of zeste homolog 2 (EZH2) has been associated
      with both non-small cell and small-cell lung cancers (SCLCs), current
      observations suggest different mechanisms of EZH2 activation and overexpression
      in these lung cancer types. Globally, SCLC kills 200,000 people yearly. New
      clinical approaches for SCLC treatment are required to improve the poor survival
      rate. Given the therapeutic potential of EZH2 as a target, we sought to delineate
      the downstream consequences of EZH2 disruption to identify the cellular
      mechanisms by which EZH2 promotes tumorigenesis in SCLC. METHODS: We generated
      cells with stable expression of short hairpin RNA targeting EZH2 and
      corresponding controls (pLKO.1) and determined the consequences of EZH2 knockdown
      on the cell cycle and apoptosis by means of propidium iodide staining and
      fluorescence-activated cell sorting, Western blot, quantitative reverse
      transcriptase-polymerase chain reaction as well as cell viability assessment
      using methylthiazol tetrazolium assays. RESULTS: We discovered that EZH2
      inhibition (1) increased apoptotic activity by up-regulating the proapoptotic
      factors Puma and Bad, (2) decreased the fraction of cells in S or G2/M phases,
      and (3) elevated p21 protein levels, implicating EZH2 in cell death and cell
      cycle control in SCLC. CONCLUSION: Our findings present evidence for the role of
      EZH2 in the regulation of cell cycle and apoptosis, providing a biological
      mechanism to explain the tumorigenicity of EZH2 in SCLC. Our work points to the
      great potential of EZH2 as a therapeutic target in SCLC.

PMID- 23857403
TI  - Pulmonary adenocarcinoma in a young patient of pulmonary langerhans cell
      histiocytosis (PLCH).

PMID- 23857404
TI  - Abscopal [corrected] effects after conventional and stereotactic lung irradiation
      of non-small-cell lung cancer.

PMID- 23857405
TI  - Successful crizotinib retreatment after crizotinib-induced interstitial lung
      disease.

PMID- 23857406
TI  - Transformation to sarcomatoid carcinoma in ALK-rearranged adenocarcinoma, which
      developed acquired resistance to crizotinib and received subsequent
      chemotherapies.

PMID- 23857407
TI  - Why denosumab obtains a survival benefit over zoledronic acid in bone metastatic
      lung cancer patients?

PMID- 23857408
TI  - "One marker does not fit all": additional translational and validation studies
      are needed to identify faithful predictors of pemetrexed activity in
      mesothelioma.

PMID- 23857409
TI  - The issue of studies evaluating biomarkers which predict outcome after pemetrexed
      based chemotherapy in malignant pleural mesothelioma.

PMID- 23857410
TI  - The dual inhibitory effect of thiostrepton on FoxM1 and EWS/FLI1 provides a novel
      therapeutic option for Ewing's sarcoma.
AB  - The poor prognosis of Ewing's sarcoma (EWS), together with its high lethal
      recurrence rate and the side-effects of current treatments, call for novel
      targeted therapies with greater curative effectiveness and substantially reduced
      side-effects. The oncogenic chimeric protein EWS/FLI1 is the key malignancy
      driver in most EWSs, regulating numerous target genes, many of which influence
      cell cycle progression. It has often been argued that targeting proteins
      regulated directly or indirectly by EWS/FLI1 may provide improved therapeutic
      options for EWS. In this context, our study examined FoxM1, a key cell cycle
      regulating transcription factor, reported to be expressed in EWS and influenced
      by EWS/FLI1. Thiostrepton, a naturally occurring small molecule, has been shown
      to selectively inhibit FoxM1 expression in cancer cells. We demonstrate that in
      EWS, in addition to inhibiting FoxM1 expression, thiostrepton downregulates the
      expression of EWS/FLI1, both at the mRNA and protein levels, leading to cell
      cycle arrest and, ultimately, to apoptotic cell death. We also show that
      thiostrepton treatment reduces the tumorigenicity of EWS cells, significantly
      delaying the growth of nude mouse xenograft tumors. Results from this study
      demonstrate a novel action of thiostrepton as inhibitor of the expression of the
      EWS/FLI1 oncoprotein in vitro and in vivo, and that it shows greater efficacy
      against EWS than against other tumor types, as it is active on EWS cells and
      tumors at concentrations lower than those reported to have effective inhibitory
      activity on tumor cells derived from other cancers. Owing to the dual action of
      this small molecule, our findings suggest that thiostrepton may be particularly
      effective as a novel agent for the treatment of EWS patients.

PMID- 23857411
TI  - Tracheo-bronchial angles in the human fetus -- an anatomical, digital, and
      statistical study.
AB  - BACKGROUND: Both the advancement of visual techniques and intensive progress in
      perinatal medicine result in performing airway management in the fetus and
      neonate affected by life-threatening malformations. This study aimed to examine
      the 3 tracheo-bronchial angles, including the right and left bronchial angles,
      and the interbronchial angle, in the fetus at various gestational ages. MATERIAL
      AND METHODS: Using methods of anatomical dissection, digital image analysis with
      an adequate program (NIS-Elements BR 3.0, Nikon), and statistics, values of the
      two bronchial angles and their sum as the interbronchial angle were semi
      automatically measured in 73 human fetuses at the age of 14-25 weeks, derived
      from spontaneous abortions and stillbirths. RESULTS: No male-female differences
      between the parameters studied were found. The 3 fetal tracheo-bronchial angles
      were found to be independent of age. The right bronchial angle ranged from 11.4
      degrees  to 41.8 degrees , and averaged 26.9+/-7.0 degrees  for the whole
      analyzed sample. The values of left bronchial angle varied from 24.8 degrees  to
      64.8 degrees , with the overall mean of 46.2+/-8.0 degrees . As a consequence,
      the interbronchial angle totalled 36.2-96.6 degrees , and averaged 73.1+/-12.7
      degrees . CONCLUSIONS: The tracheo-bronchial angles change independently of sex
      and fetal age. The left bronchial angle is wider than the right one. Values of
      the 3 tracheo-bronchial angles are unpredictable since their regression curves of
      best fit with relation to fetal age cannot be modelled. Both of the 2 bronchial
      angles and the interbronchial angle are of great relevance in the location of
      inhaled foreign bodies, and in the diagnosis cardiac diseases and mediastinal
      abnormalities.

PMID- 23857412
TI  - Exploration of conformational flexibility and hydrogen bonding of xylosides in
      different solvents, as a model system for enzyme active site interactions.
AB  - The predominantly populated conformation of carbohydrates in solution does not
      necessarily represent the biologically active species; rather, any conformer
      accessible without too large an energy penalty may be present in a biological
      pathway. Thus, the conformational preferences of a naphthyl xyloside, which
      initiates in vivo synthesis of antiproliferative glycosaminoglycans, have been
      studied by using NMR spectroscopy in a variety of solvents. Equilibria comprising
      the conformations (4)C1, (2)SO and (1)C4 were found, with a strong dependence on
      the hydrogen bonding ability of the solvent. Studies of fluorinated analogues
      revealed a direct hydrogen bond from the hydroxyl group at C2 to the fluorine
      atom at C4 by a (1h)JF4,HO2 coupling. Hydrogen bond directionality was further
      established via comparisons of fluorinated levoglucosan molecules. 

PMID- 23857413
TI  - Ti-substituted zeolite Beta: a milestone in the design of large pore oxidation
      catalysts.
AB  - The synthesis of titanium-containing zeolite Beta was first published in this
      journal in 1992 and has since proven to be groundbreaking in the development of
      large pore zeolites as heterogeneous catalysts with isolated Lewis acid sites. In
      this Viewpoint we will illustrate its significance for oxidation chemistry and
      heterogeneous catalyst design. 

PMID- 23857414
TI  - Incentivizing residents to document inpatient advance care planning.

PMID- 23857415
TI  - Distinguishing multi-voxel patterns and mean activation: why, how, and what does
      it tell us?
AB  - The introduction of multi-voxel pattern analysis (MVPA) to the functional
      magnetic resonance imaging (fMRI) community has brought a deeper appreciation for
      the diverse forms of information that can be present within fMRI activity. The
      conclusions drawn from MVPA investigations are frequently influenced by both the
      ability to decode information from multi-voxel patterns and mean activation
      levels. In practice, MVPA studies vary widely in why and how they test for
      differing overall response levels. In this article, I examine the place of
      univariate information in MVPA investigations. I first discuss the variety of
      interpretations given to finding univariate response differences. I go on to
      discuss some of the analysis approaches used to investigate and compare
      univariate and multivariate sources of information, which can illuminate their
      respective contributions. It will be important for the MVPA and general fMRI
      community to continue to discuss and debate these important issues.

PMID- 23857417
TI  - A hybrid high-speed atomic force-optical microscope for visualizing single
      membrane proteins on eukaryotic cells.
AB  - High-speed atomic force microscopy is a powerful tool for studying structure and
      dynamics of proteins. So far, however, high-speed atomic force microscopy was
      restricted to well-controlled molecular systems of purified proteins. Here we
      integrate an optical microscopy path into high-speed atomic force microscopy,
      allowing bright field and fluorescence microscopy, without loss of high-speed
      atomic force microscopy performance. This hybrid high-speed atomic force
      microscopy/optical microscopy setup allows positioning of the high-speed atomic
      force microscopy tip with high spatial precision on an optically identified zone
      of interest on cells. We present movies at 960 ms per frame displaying aquaporin
      0 array and single molecule dynamics in the plasma membrane of intact eye lens
      cells. This hybrid setup allows high-speed atomic force microscopy imaging on
      cells about 1,000 times faster than conventional atomic force microscopy/optical
      microscopy setups, and allows first time visualization of unlabelled membrane
      proteins on a eukaryotic cell under physiological conditions. This development
      advances high-speed atomic force microscopy from molecular to cell biology to
      analyse cellular processes at the membrane such as signalling, infection,
      transport and diffusion. 

PMID- 23857416
TI  - Perioperative antibiotics for prevention of acute endophthalmitis after cataract
      surgery.
AB  - BACKGROUND: Endophthalmitis is a severe inflammation of the anterior and/or
      posterior chambers of the eye that may be sterile or associated with infection.
      It is a potentially vision-threatening complication of cataract surgery.
      Prophylactic measures for endophthalmitis are targeted against various sources of
      infection. OBJECTIVES: The objective of this review was to evaluate the effects
      of perioperative antibiotic prophylaxis for endophthalmitis following cataract
      surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes
      and Vision Group Trials Register) (The Cochrane Library 2012, Issue 10), Ovid
      MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE
      Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to
      October 2012), Latin American and Caribbean Literature on Health Sciences
      (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials
      (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov)
      and the WHO International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 25 October 2012. We also searched for additional studies that cited any
      included trials using the Science Citation Index. SELECTION CRITERIA: We included
      randomized controlled trials that enrolled adults undergoing cataract surgery
      (any method and incision type) for lens opacities due to any origin. Trials that
      evaluated preoperative antibiotics, intraoperative (intracameral, subconjunctival
      or systemic) or postoperative antibiotic prophylaxis for acute endophthalmitis
      were included. We did not include studies that evaluated antiseptic preoperative
      preparations using agents such as povidone iodine, nor did we include studies
      that evaluated antibiotics for treating acute endophthalmitis after cataract
      surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed
      abstracts and full-text articles for eligibility, assessed the risk of bias for
      each included study, and abstracted data. MAIN RESULTS: Four studies met the
      inclusion criteria for this review, including 100,876 adults and 131
      endophthalmitis cases. While the sample size is very large, the heterogeneity of
      the study designs and modes of antibiotic delivery made it impossible to conduct
      a formal meta-analysis. Interventions investigated in the studies included the
      utility of adding vancomycin and gentamycin to the irrigating solution compared
      with standard balanced saline solution irrigation alone, use of intracameral
      cefuroxime and/or topical levofloxacin perioperatively, periocular penicillin
      injections and topical chloramphenicol-sulphadimidine drops compared with topical
      antibiotics alone, and mode of antibiotic delivery (subconjunctival versus
      retrobulbar injections). Two studies with adequate sample sizes to evaluate a
      rare outcome found reduced risk of endophthalmitis with antibiotic injections
      during surgery compared with topical antibiotics alone: risk ratio (RR) 0.33, 95%
      confidence interval (CI) 0.12 to 0.92 (periocular penicillin versus topical
      chloramphenicol-sulphadimidine) and RR 0.21, 95% CI 0.06 to 0.74 (intracameral
      cefuroxime versus topical levofloxacin). Another study found no significant
      difference in endophthalmitis when comparing subconjunctival versus retrobulbar
      antibiotic injections (RR 0.85, 95% CI 0.55 to 1.32). The fourth study which
      compared irrigation with balanced salt solution (BSS) alone versus BSS with
      antibiotics was not sufficiently powered to detect differences in endophthalmitis
      between groups. The risk of bias among studies was low to unclear due to
      information not being reported. AUTHORS' CONCLUSIONS: Multiple measures for
      preventing endophthalmitis following cataract surgery have been studied. One of
      the included studies, the ESCRS (European Society of Cataract and Refractive
      Surgeons) study, was performed using contemporary surgical technique and employed
      cefuroxime, an antibiotic commonly used in many parts of the world. Clinical
      trials with rare outcomes require very large sample sizes and are quite costly to
      conduct; thus, it is unlikely that additional clinical trials will be conducted
      to evaluate currently available prophylaxis. Practitioners should rely on current
      evidence to make informed decisions regarding prophylaxis choices.

PMID- 23857418
TI  - Is sucralose ingestion acceptable before 18F-FDG PET/CT imaging?

PMID- 23857419
TI  - A portable database of adverse reactions and drug interactions with
      radiopharmaceuticals.
AB  - Our objective was to develop a software application that allows us to easily
      manage a portable database of information on radiopharmaceutical interactions
      with drugs or other agents and on radiopharmaceutical adverse effects. METHODS:
      The application was developed and compiled with a commercially available data
      management system and programming language. All data entered into the database
      came from the scientific literature and were accompanied by their bibliographic
      references. RESULTS: We developed the database, which we have called Datinrad. To
      date, it contains 275 drug interactions and 44 records of adverse reactions to
      radiopharmaceuticals. CONCLUSION: Datinrad contains all the information published
      to date on drug-radiopharmaceutical interactions and adverse effects of
      radiopharmaceuticals and allows users to introduce new data from future
      publications. The collection of these data and their easy availability to all
      nuclear medicine personnel will be useful in the recognition of a possible
      adverse reaction or drug interaction that may alter the radiopharmaceutical
      biodistribution and lead to a misdiagnosis. This open-access database application
      is available free of charge in both English and Spanish at www.radiopharmacy.net.

PMID- 23857420
TI  - Lumbar nerve root injections: a prospective cohort outcomes study comparing age-
      and gender-matched patients who returned an outcomes-based postal questionnaire
      with patients who did not return the postal questionnaire.
AB  - OBJECTIVE: The purpose of this study is to investigate if relying on postal
      questionnaires returned by patients provides an accurate representation of
      reported outcomes from patients receiving imaging-guided lumbar nerve root
      injections (NRIs). MATERIALS AND METHODS: Patients who received imaging-guided
      transforaminal lumbar NRIs were given short questionnaires inquiring about pain
      level [numerical rating scale (NRS)] and overall improvement [Patient's Global
      Impression of Change (PGIC)]. Those who did not return the questionnaires (non
      responders) were telephoned and asked about pain level and overall change in
      condition. Age and gender matching of responders and non-responders resulted in
      97 patients in each group. The proportion of patients reporting clinically
      relevant "improvement" or "worsening" in each group was calculated and the Chi
      square test was used to detect differences. NRS and PGIC scores for responders
      and non-responders were compared using Student's t test and the Mann-Whitney U
      test, respectively. RESULTS: A higher proportion of non-responders reported
      clinically relevant improvement (53.6 %) compared to responders (42.6 %) and
      responders reported significantly higher levels of worsening of condition (p =
      0.01). Both responders and non-responders had significant (p <= 0.05) improvement
      on the 20-30-min and 1-month NRS scores compared to their pre-injection baseline
      scores. Non-responders had significantly higher baseline NRS scores but no
      significant difference at the 20-30-min and 1-month NRS scores compared to
      responders. CONCLUSIONS: Patients returning postal questionnaires reported less
      favorable outcomes compared to those who did not return their questionnaires.

PMID- 23857421
TI  - How to read post-operative radiographs and CT scans after single-bundle anterior
      cruciate ligament reconstruction.
AB  - Reconstruction of the anterior cruciate ligament (ACL) is a well-established
      surgical procedure. However, post-operative imaging in the early phase is not
      routinely performed. The rationale for performing such imaging is to provide a
      baseline examination for future controls, to provide immediate feedback to
      surgeons regarding tunnel placement, and to assess placement of fixation devices.
      The purpose of this paper is to enable the reader to accurately read post
      operative radiographs and CT scans after single-bundle ACL reconstruction. 

PMID- 23857422
TI  - The physiological range of femoral antetorsion.
AB  - INTRODUCTION: Intramedullary nailing is a common method for fixation of femoral
      diaphyseal shaft fractures. However, postoperative malrotation does occur in 20
      30 % of patients, as intraoperative assessment of antetorsion remains difficult.
      The estimated average antetorsion angle is 15 degrees . However, it is not clear
      whether antetorsion correlates with individual characteristics such as age,
      gender, or femoral length. This information may help surgeons to better estimate
      the correct target rotation before and during surgery. MATERIALS AND METHODS: The
      antetorsion of 211 healthy femurs was measured using torsion difference CTs
      according to the technique published by Jend. Correlations with age, gender, and
      femoral length were calculated. RESULTS: A significant negative correlation of
      age and antetorsion was found for women aged 0-20. Older women and men did not
      show any correlation between antetorsion and age. There was no correlation
      between antetorsion and femoral length. Mean values differed between 17.8 degrees
      +/- 8.9 degrees  and 22.7 degrees  +/- 10.7 degrees  in women and 15.3 degrees 
      +/- 8.0 degrees  and 21.4 degrees  +/- 9.7 degrees  in men. CONCLUSIONS:
      Antetorsion is mostly independent of body height and age, the latter except in
      women younger than 20. The so-far-estimated physiologic antetorsion of about 15
      degrees  seems to be a little higher in most people.

PMID- 23857423
TI  - External pneumatic compression device prevents fainting in standing weight
      bearing MRI: a cohort study.
AB  - OBJECTIVE: To investigate if a peristaltic external pneumatic compression device
      attached to the legs, while scanning, can reduce a substantial risk of fainting
      in standing weight-bearing magnetic resonance imaging (MRI). MATERIALS AND
      METHODS: This study comprised all patients with low back pain referred to
      standing MRI of the lumbar spine, using a 0.25-T open G-Scanner, from June 2011
      to April 2012. The standing MRI protocol included a sagittal TSE T2w and an axial
      GRE T2w sequence giving a total scan time of 17 min. The first patients were
      scanned standing without a device (control group), and then from January to April
      2012 the patients were scanned in the standing position using an external
      pneumatic compression device, attached to the legs (experimental group). RESULTS:
      One hundred and forty-nine patients (mean age 42.5, standard deviation 12.5, and
      range 20-77 years) were included and scanned standing. No significant difference
      in age (p = 0.51) or gender (p = 0.47) was observed between the control group (n
      = 86) and the experimental group (n = 63). Sixteen patients (19 %) fainted in the
      control group during the standing MRI scan, compared to one patient (2 %) in the
      experimental group where the pneumatic compression device was applied. The
      difference between groups was highly significant (p = 0.001; Fisher's exact
      test), with an OR = 0.071 (exact 95 % CI: 0.002 to 0.486) for the pneumatic
      compression device. CONCLUSIONS: A substantial risk of fainting during standing
      MRI was almost eliminated by using an external peristaltic pneumatic compression
      device.

PMID- 23857424
TI  - The use of 50% albumin/plasma replacement fluid in therapeutic plasma exchange
      for thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is caused by a
      deficiency of von Willebrand factor-cleaving protease (ADAMTS13) and is often
      associated with the presence of an antibody inhibiting the activity of the
      protease. Typically, 1-1.5 plasma volume exchanges are performed daily until
      symptoms have resolved and the platelet count exceeds 150,000/ul. Plasma is the
      usual replacement fluid as it provides a source of functional ADAMTS13, thus
      exposing patients to large volumes of plasma. Historically, Puget Sound Blood
      Center (PSBC) has performed therapeutic plasma exchange (TPEs) for TTP using 5%
      albumin for the first half of the procedure followed by plasma for the remainder.
      We sought to assess the efficacy of this approach. STUDY DESIGN AND METHODS: All
      TPEs performed for the diagnosis of TTP by the PSBC apheresis service from
      January 1, 2004 through December 31, 2011 were reviewed. Response time, remission
      rates, relapses, and adverse events were evaluated for those patients with
      documented ADAMTS13 levels <=10%. Comparisons were made with published data on
      TTP patients treated using 100% plasma replacement. RESULTS: Twenty-one patients
      required a median of 11 TPEs. Median time to response was 14 days. Ninety percent
      of patients responded to TPE. Among patients achieving remission, 53% relapsed.
      Out of 283 total procedures, there were 74 procedures with a documented adverse
      event (26%), mostly mild allergic reactions. CONCLUSIONS: TPE with an
      albumin/plasma replacement is safe and well-tolerated. Remission and relapse
      rates were comparable to those reported using 100% plasma replacement.

PMID- 23857425
TI  - The human impact of floods: a historical review of events 1980-2009 and
      systematic literature review.
AB  - Background. Floods are the most common natural disaster and the leading cause of
      natural disaster fatalities worldwide. Risk of catastrophic losses due to
      flooding is significant given deforestation and the increasing proximity of large
      populations to coastal areas, river basins and lakeshores. The objectives of this
      review were to describe the impact of flood events on human populations in terms
      of mortality, injury, and displacement and, to the extent possible, identify risk
      factors associated with these outcomes. This is one of five reviews on the human
      impact of natural disasters Methods. Data on the impact of floods were compiled
      using two methods, a historical review of flood events from 1980 to 2009 from
      multiple databases and a systematic literature review of publications ending in
      October 2012. Analysis included descriptive statistics, bivariate tests for
      associations and multinomial logistic regression of flood characteristics and
      mortality using Stata 11.0. Findings. There were 539,811 deaths (range: 510,941
      to 568,680), 361,974 injuries and 2,821,895,005 people affected by floods between
      1980 and 2009. Inconsistent reporting suggests this is an underestimate,
      particularly in terms of the injured and affected populations. The primary cause
      of flood-related mortality is drowning; in developed countries being in a motor
      vehicle and male gender are associated with increased mortality, whereas female
      gender may be linked to higher mortality in low-income countries. Conclusions.
      Expanded monitoring of floods, improved mitigation measures, and effective
      communication with civil authorities and vulnerable populations has the potential
      to reduce loss of life in future flood events. 

PMID- 23857426
TI  - Determination of free amino acids in African gourd seed milks by capillary
      electrophoresis with light-emitting diode induced fluorescence and laser-induced
      fluorescence detection.
AB  - A CE technique coupled to LIF detection (488 nm) or LED-induced fluorescence
      detection (470 nm) has been evaluated to acquire a cheap way to analyze amino
      acids (AAs) whilst maintaining the best sensitivity. To quantitate AAs in milk of
      Cucurbitaceae of Sub-Saharan Africa, they were labeled with FITC. We used an
      optimized separation buffer composed of 30 mM boric acid buffer adjusted to pH
      9.3 with NaOH (1 M) containing 12 mM SDS and 5% ethylene glycol v/v; prior to the
      injections, the derivatized samples are diluted 100 times. The LOQs in the sample
      are Arg: 1.1 MUM, Ala: 3.5 MUM, and Glu 8.9 MUM. Cucumeropsis mannii (CM) Naudin
      and Citrullus lanatus (CL) are vegetable sources rich in proteins and AAs of high
      quality. Our analyses have led to the identification of 11 AAs in CL and CM
      milks. Phe, Trp, and Ala are predominant in the two types of lyophilized milks,
      while Asp and Val demonstrate very low contents. Six essential AAs (Phe, Thr,
      Val, Trp, Ile, and Leu) are present in both types of extracts, but lysine was not
      detected, indicating that this AA is missing in gourd milk. These results should
      be useful in efforts to complement or replace very expensive cow milk or the less
      appreciated soya milk with milk from available local agroressources. 

PMID- 23857427
TI  - Radiologic course of primary sclerosing cholangitis: assessment by three
      dimensional magnetic resonance cholangiography and predictive features of
      progression.
AB  - Magnetic resonance imaging (MRI) with magnetic resonance cholangiography (MRC)
      has become the radiologic standard of reference for diagnosis of primary
      sclerosing cholangitis (PSC). However, natural history of radiologic features of
      PSC is poorly known. In the current study, we aimed at analyzing the course of
      PSC using three-dimensional (3D) MRC and liver MRI to find predictive radiologic
      features of progression. PSC patients, followed up in our center, with at least
      two 3D MRCs performed in at least a 1-year interval, were retrospectively
      reviewed. We built an interpretation standard model to score precisely bile ducts
      and liver parenchyma features. The primary endpoint was overall radiologic
      course, including worsening, improvement, or stabilization. Radiologic features
      were analyzed by logistic regression. We reviewed 289 MRIs from 64 patients upon
      a mean radiologic follow-up of 4 years (range, 1-9). Radiologic features worsened
      in 37 patients (58%) and stabilized in 27 (42%); no patient showed improvement.
      Multivariate analysis resulted in two MRI progression risk scores, based on the
      combination of predictive radiologic features (score without gadolinium
      administration = 1 * dilatation of intrahepatic bile ducts + 2 * dysmorphy + 1 *
      portal hypertension; score with gadolinium administration = 1 * dysmorphy + 1 *
      parenchymal enhancement heterogeneity). These scores were associated with
      radiologic progression, with an area under the curve of 80 and 83% +/- 4%.
      CONCLUSION: A majority of PSC patients develop radiologic aggravation upon MRI
      over 4 years. Two simple scores can predict radiologic progression.

PMID- 23857429
TI  - Physicians' views on the professional roles of pharmacists in patient care in
      Eritrea.
AB  - OBJECTIVE: A collaborative relationship between physicians and pharmacists is
      crucial in the patient oriented role of pharmacists. In order to get an optimal
      patient outcome, strong cooperation between pharmacists and physicians is
      necessary. It is evident that in patient-oriented activities of pharmacists,
      their roles should be appropriately perceived and welcomed by physicians. This
      survey, thus, aimed to explore the perception of Eritrean physicians towards the
      professional roles of pharmacists in patient care. SETTING: The study was
      conducted in all hospitals in Asmara. METHOD: A self administered questionnaire
      was distributed to the physicians working in Asmara hospitals. The instrument
      contained questions to evaluate the physicians' level of agreement using a 5
      point Likert type scale. MAIN OUTCOME MEASURE: Opinions of physicians on the
      professional role of pharmacists. RESULTS: Out of the 55 questionnaires
      distributed 50 were completed and returned, giving a response rate of 90.91 %.
      Most of the physicians accepted the reprofessionalization of pharmacy profession
      (88 %); majority disagreed that pharmacists are using their full potential in
      patient care (60 %); physicians strongly agreed or agreed that they should accept
      pharmacists' recommendations on patients' medication (96 %). CONCLUSIONS:
      Generally the physicians appreciated the professional role of pharmacists in
      patient care. They agreed with the idea of re-professionalization of pharmacy
      into patient care. For conclusive evidence nationwide study is recommended.

PMID- 23857430
TI  - Drug related problems and pharmacist interventions in a geriatric unit employing
      electronic prescribing.
AB  - BACKGROUND: Computerised physician order entry (CPOE) and the integration of a
      pharmacist in clinical wards have been shown to prevent drug related problems
      (DRPs). OBJECTIVES: The primary objective was to make an inventory of the DRPs
      and resident pharmacist on-ward interventions (PIs) identified in a geriatric
      acute care unit using CPOE system. The secondary objective was to evaluate the
      physicians' acceptance of the proposed interventions. SETTING: A 26-bed geriatric
      ward of a 1,300-bed teaching hospital. METHOD: A 6-month descriptive study with
      prescription analysis and recommendations to physicians by a resident pharmacist
      during five half days a week. MAIN OUTCOME MEASURES: Patients' characteristics,
      number of prescribed drugs per patient, nature and frequency of DRPs and PIs,
      physicians' acceptance and drugs questioned. RESULTS: Resident pharmacist
      reviewed 311 patients and identified 241 DRPs. One hundred and fifty-two patients
      (49 %) had at least one DRP (mean +/- SD age 87 +/- 6 years, mean +/- SD number
      of prescribed drugs 10.7 +/- 3.4). Most frequent DRPs were: untreated indication
      (n = 58, 24.1 %), dose too high (n = 46, 19.1 %), improper administration (n =
      31, 12.9 %) and drug interactions (n = 23, 9.5 %). The rate of physicians'
      acceptance was 90.0 % (7.5 % refusals, 2.5 % not assessable). DRPs related to
      CPOE system misuse (n = 35, 14.5 %) appeared as a worrying phenomenon (e.g.,
      errors in selecting dosage or unit, or duplication of therapy). CONCLUSION: A
      resident pharmacist detected various DRPs. Most PIs were accepted. DRPs related
      to the misuse of the CPOE system appeared potentially dangerous and need
      particular attention by healthcare professionals. The description of the DRPs is
      an essential step for implementation of targeted clinical pharmacy services in
      order to optimize pharmacists' job time.

PMID- 23857431
TI  - Sulindac and Celecoxib regulate cell cycle progression by p53/p21 up regulation
      to induce apoptosis during initial stages of experimental colorectal cancer.
AB  - In the present study we have elaborated the putative mechanisms could be followed
      by the non-steroidal anti-inflammatory drugs (NSAIDs) viz. Sulindac and Celecoxib
      in the regulation of cell cycle checkpoints along with tumor suppressor proteins
      to achieve their chemopreventive effects in the initial stages of experimental
      colorectal cancer. Male Sprague-Dawley rats were administered with 1,2
      dimethylhydrazine dihydrochloride (DMH) to produce early stages of colorectal
      carcinogenesis. The mRNA expression profiles of various target genes were
      analyzed by RT-PCR and validated by quantitative real-time PCR, whereas protein
      expression was analyzed by Western blotting. Nuclear localization of
      transcription factors or other nuclear proteins was analyzed by electrophoretic
      mobility shift assay and immunofluorescence. Flowcytometry was performed to
      analyze the differential apoptotic events and cell cycle regulation. Molecular
      docking studies with different target proteins were also performed to deduce the
      various putative mechanisms of action followed by Sulindac and Celecoxib. We
      observed that DMH administration has abruptly increased the proliferation of
      colonic cells which is macroscopically visible in the form of multiple plaque
      lesions and co-relates with the disturbed molecular mechanisms of cell cycle
      regulation. However, co-administration of NSAIDs has shown regulatory effects on
      cell cycle checkpoints via induction of various tumor suppressor proteins. We may
      conclude that Sulindac and Celecoxib could possibly follow p53/p21 mediated
      regulation of cell proliferation, where down regulation of NF-kappaB signaling
      and activation of PPARgamma might serve as important additional events in vivo. 

PMID- 23857433
TI  - Health care utilization differences between women and men after employers switch
      to high-deductible plans: a cause for concern?

PMID- 23857432
TI  - Hospicells promote upregulation of the ATP-binding cassette genes by insulin-like
      growth factor-I via the JAK2/STAT3 signaling pathway in an ovarian cancer cell
      line.
AB  - Interaction between tumor cells and their micro-environment has a crucial role in
      the development, progression and drug resistance of cancer. Our objective was to
      confirm the role of Hospicells, which are stromal cells from the cancer
      microenvironment, in drug resistance and tumor cell growth. We demonstrated that
      soluble factors secreted by Hospicells activate several genes and upregulate the
      JAK/STAT signaling pathway in ovarian cancer cell lines. Hospicells express all
      insulin-like growth factor (IGF) family as detected by gene array, RT-PCR,
      protein array and immunocytochemistry. While focusing attention on the
      microenvironment, we considered the role of IGF-I in proliferation and survival
      of ovarian cancer cells. Indeed, IGF-I is a major regulator of different stages
      of cancer development. We studied the effect of exogenously added IGF-I on the
      regulation of ATP-binding cassette (ABC) genes (MDR1, MRP1, MRP2, MRP3, MRP5 and
      BCRP) in the ovarian cancer cell line OVCAR3 and validated the results obtained
      using the IGF-IR antagonist picropodophyllin. IGF-I regulates the expression of
      ABC genes in OVCAR3 cells via the PI3-kinase, MEK and JAK2/STAT3 signaling
      pathways. The OVCAR3 cell line when co-cultured with Hospicells showed a marked
      degree of drug resistance. The drug resistance observed could be amplified with
      exogenous IGF-I. Addition of IGF-IR inhibitor, however, reduced the degree of
      resistance in these exposed cells. Cells that were treated with anticancer drugs
      and then exposed to IGF-I showed an increase in drug resistance and, thereby, an
      increase in cell survival. This observation indicates that drug resistance of
      OVCAR3 cells increases when there is synergy between OVCAR3 cells and Hospicells
      and it is amplified when IGF-I was exogenously added. In conclusion, inhibition
      of IGF-IR and targeting of the JAK2/STAT3 signaling pathway can be a target for
      ovarian cancer therapy.

PMID- 23857434
TI  - Walkable dual emissions.
AB  - Walkable dual emissions, in which the emission bands of the walker reversibly
      cross or leave those of the stationary ones depending on temperature and
      concentration, have been demonstrated in cyclic dimeric lanthanide complexes
      [Ln(hfac)3(PAnPO2)]2 (Ln = Eu(III), Tb(III); hfac(-) = hexafluoroacetylacetonate;
      PAnPO2 = 9,10-bis(diphenylphosphino) anthracene dioxide), providing a concept
      model for signals exchanging and dispatching. Additionally, good linear
      relationships are observed between the maximum emission bands of the walker vs
      the concentrations {lg(M)} and the measurement temperatures (K), implying such
      materials could be served as potential concentration and temperature sensors. 

PMID- 23857435
TI  - Constant-pressure simulations of Gay-Berne liquid-crystalline phases in
      cylindrical nanocavities.
AB  - Applications of liquid crystals (LCs) are based on controlling the orientational
      and translational order of the medium. One important way of control is via
      confinement. In this work, uniaxial thermotropic LCs confined to nanosized
      cylindrical cavities are studied using isobaric parallel tempering (PT) Monte
      Carlo (MC) simulations. The LCs are modeled using the Gay-Berne (4.4, 20.0, 1, 1)
      (GB) potential in long, smooth-walled cavities. The chosen particle-wall
      interaction favours homogeneous planar anchoring - the alignment of molecules
      along the wall. We report the results for the phase structure appropriate to
      three different cavity sizes as well as comparison to the results of bulk
      simulations. Ensemble averages for orientational and translational order
      parameters as well as their local behavior as a function of the distance to the
      cavity wall is calculated by reweighting results from all the simulated
      temperatures. We find that the LC director tends to align strongly with the axis
      of the cylindrical cavity. The orientational order is enhanced and translational
      order suppressed by the walls of the cavity. Hence, there are notable differences
      between the local order close to the wall and near the cylinder axis. The
      position-dependent distributions of the order parameters result in smooth phase
      transitions in their respective system-wide averages. Particularly, the nematic
      isotropic (N-I) transition is replaced by a continuous nematic-paranematic (N-PN)
      transition. This is caused by the core region of the cavities becoming isotropic
      at high temperatures, whereas near the wall the LC retains nematic order. In
      contrast to previous NVT ensemble simulations, we find the effect of confinement
      on the smectic (Sm) layering to be weak. Also, Sm-N and N-PN transitions are
      found to be both sharper and residing at higher temperatures than in the constant
      volume simulations. At temperatures where the bulk LC is a solid, we observe a
      wall-induced density wave in the confined systems, which outweighs the self
      organization of the LC to hexagonal in-plane order. 

PMID- 23857436
TI  - Randomized controlled comparison of combined general and epidural anesthesia
      versus general anesthesia on diaphragmatic function after laparoscopic
      prostatectomy.
AB  - BACKGROUND: Little is known about the effect of anesthetic technique on
      postoperative diaphragmatic function, which is associated with postoperative
      morbidity and recovery in patients undergoing laparoscopic pelvic surgery. The
      aim of this trial was to study the effect of combined general and epidural
      anesthesia versus general anesthesia on postoperative diaphragmatic function
      measured by ultrasonography in patients undergoing robot-assisted laparoscopic
      radical prostatectomy (RALRP). METHODS: Fifty-four patients undergoing RALRP were
      enrolled prospectively. Study population was randomized to receive general (group
      G, N.=27) or combined general and epidural (group GE, N.=27) anesthesia.
      Diaphragmatic inspiratory amplitude (DIA), and inspiration and expiration time
      (Ti and Te, respectively) were measured by M-mode ultrasonography during
      quiet/deep breathing and sniffing before the surgery and on postoperative days
      (POD) 1 and 2. Diaphragmatic inspiratory and expiratory velocities (DIV and DEV)
      were also calculated (DIA/Ti and DIA/Te, respectively). Spirometry was performed
      in addition to ultrasonography. RESULTS: DIA during deep breathing and sniffing
      was significantly decreased on POD 1 in group G, while it was preserved in group
      GE. These reductions in diaphragmatic function were restored to preoperative
      values on POD 2 in both groups. Vital capacity and peak expiratory flow were
      diminished in group G on POD 1 and 2. However, spirometry revealed no impairment
      in group GE except for vital capacity on POD 1. The correlation coefficients (R2)
      between diaphragmatic function and spirometry variables ranged from 0.231 to
      0.286. Postoperaitve pain was comparable. CONCLUSION: Combined general and
      epidural anesthesia may attenuate the severity of postoperative diaphragmatic
      dysfunction after RALRP compared to conventional general anesthesia.

PMID- 23857437
TI  - Role of fibrinogen in massive injury.
AB  - Coagulation is a complex cascade whose intact functioning is essential in helping
      control hemorrhage after injury. While traditionally ascribed to the combined
      effects of acidosis, hypothermia, factor consumption and factor dilution,
      coagulopathy is also directly related to injury as well as hypofibrinogenemia and
      hyperfibrinolysis. Low fibrinogen concentration is readily determined with
      standard laboratory profiling, but direct analysis of hyperfibrinolysis relies on
      either thromboelastography or rotational thromboelastometry. Both conditions
      offer opportunities for therapeutic intervention, and inhibition or abrogation of
      hyperfibrinolysis in particular may significantly improve survival in patients
      with injury and massive hemorrhage. Herein, we explore the underpinnings of
      trauma associated coagulopathy, the basic science behind the role of fibrinogen
      in acute traumatic coagulopathy, and the rationale behind and the data derived
      from management of hypofibrinogenemia as well as hyperfibrinolysis. 

PMID- 23857438
TI  - Blood from the right atrium may provide closer estimates of mixed venous
      saturation than blood from the superior vena cava. A pilot study.
AB  - BACKGROUND: As a rule, central venous catheters (CVC) should not be positioned in
      the right atrium (RA) to avoid the risk of perforation and cardiac tamponade.
      However, in ICUs where ECG monitoring can detect any initial damage of the atrial
      wall, CVCs may probably be safely positioned in the RA. We investigated whether
      mixed venous saturation (SvO2) was better estimated by measuring central venous
      saturation (ScvO2) in the RA or in the superior vena cava (SVC) in patients
      undergoing cardiac surgery. METHODS: A CVC and a pulmonary artery catheter (PAC)
      were positioned before surgical coronary revascularization in sixty patients.
      Under transesophageal echocardiographic guidance, CVC tips were randomly
      positioned inside the RA (group A) or the SVC (group C). In each patient, eight
      pairs of blood samples were collected from CVC and PAC distal ports and
      saturation measured. Cardiac arrhythmias that occurred in the first 48
      postoperative hours and CVC tip position on chest X-rays were also registered.
      RESULTS: ScvO2 and SvO2 correlated better in group A (r=0.95) than in group C
      (r=0.84). The 95% interval of confidence of the gap between ScvO2 and SvO2 was
      narrower in group A (-6.9/+ 3.2 vs. -11.6/+5.5; p<.01). The incidence of
      arrhythmias was equal in the two groups (16.7%). On chest X-rays, CVC tips were
      5.4 (SD=3.6) cm below the tracheal carina in group A and 5.3 (SD=3.9) cm in group
      C. CONCLUSION: In monitored patients, positioning CVC tips in the RA rather than
      in the SVC may allow closer estimates of SvO2 and may be safe. Yet, safety should
      be confirmed by further studies with larger samples of patients.

PMID- 23857439
TI  - Elevated adipose tissue lactate to pyruvate (L/P) ratio predicts poor outcome in
      critically ill patients with septic shock: a microdialysis study.
AB  - BACKGROUND: Sepsis is a disease affecting tissue metabolism; in vivo
      microdialysis (MD) is a bedside technique enabling researchers to monitor tissue
      metabolic changes. We conducted this study aiming to evaluate the relationship
      between lactate to pyruvate (L/P) ratio, a sensitive marker of tissue oxygenation
      and perfusion, and mortality in critically ill septic patients. METHODS: We
      enrolled 105 patients with septic shock hospitalized in the mixed intensive care
      unit of a tertiary hospital. A MD catheter was inserted in the subcutaneous
      adipose tissue of the upper thigh and interstitial fluid samples were collected
      and analyzed for glucose, lactate, pyruvate, and glycerol. RESULTS: Multivariate
      regression analysis showed that among variables registered on day 1, APACHE II
      and SOFA scores, blood lactate and microdialysis-assessed tissue L/P ratio were
      independently associated with 28-day mortality. Even in patients with normal (<2
      mmol/L) blood lactate, adipose tissue L/P ratio showed a strong trend to
      statistical significance. During the 6-day study period, non-survivors had
      significantly higher L/P ratios compared to survivors (P=0.001) and mixed model
      analysis revealed a different pattern of evolution in time with non-survivors
      experiencing an increase while survivors had a late decline in their L/P ratio.
      The AUC for L/P ratio was similar to that of APACHE II (P=0.67) and SOFA score
      (P=0.73). Comparison of the Kaplan-Meier 28-day survival curves of patients with
      normal (<= 25) versus elevated (>25) L/P ratios showed that the latter survived
      significantly less (P=0.02; log-rank test). CONCLUSION: Elevated adipose tissue
      L/P ratio is associated with poor outcome in critically ill patients with septic
      shock. Microdialysis deserves to be further studied as a research tool in the
      multi-modal monitoring of septic critically ill patients.

PMID- 23857440
TI  - Comparison of three high flow oxygen therapy delivery devices: a clinical
      physiological cross-over study.
AB  - AIM: High-flow-oxygen-therapy is provided by various techniques and patient
      interfaces, resulting in various inspired-fraction of oxygen (FiO2) and airway
      pressure levels. However, tracheal measurements have never been performed.
      METHODS: Three oxygen-delivery-devices were evaluated: 1) standard-high-flow
      oxygen-facemask with reservoir-bag, 2) Optiflow(TM)-high-flow-nasal-cannulae and
      3) Boussignac(TM)-oxygen-therapy-system. Main judgment criteria were airway
      pressure and FiO2 measured in the trachea. The three devices were randomly
      evaluated in cross-over in 10 Intensive-Care-Unit patients using three oxygen
      flow-rates (15, 30 and 45 L/min) and two airway-tightness conditions (open and
      closed mouth). Airway-pressures and FiO2 were measured by a tracheal-catheter
      inserted through the hole of a tracheotomy tube. Comfort was evaluated by self
      reporting. Data are presented as median [25-75th]. RESULTS: 1) Regarding oxygen
      delivery devices, BoussignacTM provided the highest mean tracheal pressure (13.9
      [10.4-14.5] cmH20) compared to Optiflow(TM) (2 [1-2.3] cmH2O, P<0.001).
      BoussignacTM provided both positive inspiratory and expiratory airway-pressures,
      whereas Optiflow(TM) provided only positive expiratory airway-pressure. Reservoir
      bag-facemask provided airway pressure close to zero. For FiO2, highest value was
      obtained for both Optiflow(TM) and facemask (90%) compared to Boussignac(TM)
      (80%), P<0.01. 2) Regarding oxygen-flow, airway-pressure and FiO2 systematically
      increased with oxygen-flow with the three devices except airway-pressure for the
      facemask. 3) Regarding the open-mouth position, mean airway-pressure decreased
      with Optiflow(TM) only (2 [1.2-3.3] vs. 0.6 [0.3-1] cmH2O, P<0.001). Opening the
      mouth had little impact on FiO2. 4) finally, discomfort-intensities were low for
      both Optiflow(TM) and reservoir-bag-facemask compared to Boussignac(TM), P<0.01.
      CONCLUSION: On one hand, Boussignac(TM) is the only device that generates a
      relevant positive-airway-pressure during both inspiration-and-expiration,
      independently of mouth-position. Optiflow(TM) provides a low positive-airway
      pressure (<4 cmH2O), highly dependent of mouth-closing. The reservoir-bag
      facemask provides no positive-airway-pressure. On the other hand, FiO2 are
      slightly but significantly higher for Optiflow(TM) and reservoir-bag-facemask
      than for Boussignac(TM). Discomfort was lesser for Optiflow(TM) and reservoir-bag
      facemask.

PMID- 23857441
TI  - Can the incidence of accidental dural puncture in laboring women be reduced? A
      systematic review and meta-analysis.
AB  - BACKGROUND: Accidental dural puncture (ADP) after epidural analgesia (EDA) for
      labor pain may cause severe postdural puncture headache (PDPH) and may prolong
      hospital stay. We aimed to identify techniques that reduce the incidence of ADP.
      METHODS: A systematic literature search was performed. Data on the occurrence of
      ADP and PDPH were extracted and subjected to meta-analysis. The random effects
      model was applied. Risk ratios (RR) and 95% confidence intervals (CI) were
      calculated. RESULTS: We identified 54 articles, 13 non-randomized controlled
      trials and 41 randomized controlled trials (RCTs), reporting on a total of 98,869
      patients. In non-RCTs, the use of liquid for the identification of the epidural
      space was associated with a reduced risk of ADP compared to the use of air (RR
      0.55, 95% CI 0.39 to 0.79, P=0.001). In our analysis of RCTs this comparison did
      not produce a significant difference. No effect was found for combined spinal
      epidural analgesia, maternal position, type of the catheter, needle size, bevel
      direction, operator experience, or use of ultrasound. CONCLUSION: A reduction of
      the risk of ADP was found for liquid use for the loss of resistance, but only in
      lower quality studies. Based on current evidence, we cannot make a recommendation
      regarding any of the techniques under study. Therefore, clinicians should focus
      on measures to prevent or treat PDPH once ADP has occurred.

PMID- 23857442
TI  - Acute respiratory failure in neutropenic patients is associated with a high post
      ICU mortality.
AB  - BACKGROUND: Few studies have evaluated outcomes of neutropenic patients admitted
      to the ICU at the onset of acute respiratory failure (ARF). The main objective of
      this study was to describe outcomes and to identify early predictors of hospital
      mortality in critically ill cancer patients with ARF during chemotherapy-induced
      neutropenia. METHODS: Retrospective analysis of prospectively collected data
      extracted from two recent prospective multicentre studies. We included
      neutropenic adults admitted to the ICU for ARF. RESULTS: Of the 123 study
      patients, 107 patients (87%) had haematological malignancies; 78 (64%) were male,
      median age was 57 years (44-62), and median LOD score at ICU admission was 6 (4
      9). ICU and hospital mortality rates were 42% and 77%, respectively. Endotracheal
      mechanical ventilation was an independent risk factor for hospital mortality
      (odds ratio [OR], 7.73; 95% confidence interval [95%CI], 2.52-23.69); two factors
      independently protected from hospital mortality, namely, ICU admission for ARF
      during neutropenia recovery (OR, 0.23; 95%CI, 0.07-0.73) and steroid therapy
      before ICU admission (OR, 0.35; 95%CI, 0.11-0.95). CONCLUSION: Our study
      demonstrates a meaningful ICU survival in the studied population and identified
      factors associated with ICU and hospital mortality. Further work is needed to
      address the reasons for the high post-ICU mortality rate after ARF.

PMID- 23857443
TI  - Mental and physical disability after sepsis.
AB  - Sepsis remains a major cause of admissions to Intensive Care Units (ICU) and has
      a high mortality rates and significant morbidity in survivors. There are
      physical, cognitive and psychological sequelae from severe sepsis that have a
      negative effect on the patients' health related quality of life in the longer
      term and a social care and humanitarian impact. Although muscle mass loss during
      the septic period happens very quickly, recovery takes a considerable time and
      requires the patient to commit to exercising and eating well to rebuild. Where
      cognitive impairment has resulted from the septic illness the patients' ability
      to look after themselves may be affected and this has financial and family
      implications for future care. Patients may also develop psychological problems
      such as anxiety, depression or post traumatic stress disorder (PTSD), which can
      have a profound effect on their everyday functioning and the possibility of
      returning to work. As yet there are no published studies of rehabilitation with
      patients surviving severe sepsis, although there is one in progress at the
      moment. The use of techniques such as ICU diaries to help patients to understand
      their illness and deal with delusional memories they may have from their ICU stay
      has been shown to aid psychological recovery in general ICU patients, a
      percentage of whom will have suffered from sepsis. The use of a self-guided
      manualised 6 week rehabilitation program, the ICU Recovery Manual, has been shown
      to accelerate physical recovery in general ICU patients. Considerable amounts of
      money are spent treating patients with severe sepsis in ICU and not completing
      the job of returning them to as close as possible to their normal functioning
      does not make financial sense. 

PMID- 23857444
TI  - Fatal pulmonary lymphomatoid granulomatosis in a patient taking methotrexate for
      rheumatoid arthritis.

PMID- 23857445
TI  - Chronic pain management in pregnancy and lactation.
AB  - During pregnancy most of women will experience some kind of pain, either as a
      result of a pre-existing condition (low back pain, headache, fibromyalgia, and
      rheumatoid arthritis) or as a direct consequence of pregnancy (weight gain,
      postural changes, pelvic floor dysfunction, hormonal factors). However, chronic
      pain management during pregnancy and lactation remains a challenge for clinicians
      and pregnant women are at risk of undertreatment for painful conditions, because
      of fear about use of drugs during pregnancy. Few analgesic drugs have been
      demonstrated to be absolutely contraindicated during pregnancy and breastfeeding,
      but studies in pregnant women are not available for most of pain medications. The
      aim of this paper is to review the safety profile in pregnancy or lactation of
      the commonly prescribed pain medications and non-pharmacological treatments. In
      addition to the conventional classifications from the Food and Drug
      Administration and the American Academy of Paediatrics, authors analyzed the
      currently available clinical data from literature. 

PMID- 23857446
TI  - Management of refractory hypoxemia in ARDS.
AB  - Severe hypoxemia is the hallmark of ARDS. However, unmanageable refractory
      hypoxemia fortunately is a rare occurrence in patients with ARDS and an
      infrequent cause of death in ARDS. However, in some patients, in spite of the
      application of lung protective ventilation with moderate to high levels of end
      expiratory pressure (PEEP), refractory hypoxemia remains unresolved. When
      refractory hypoxemia persists, we first recommend the use of lung recruitment
      maneuvers and a decremental PEEP trial, if this does not resolve the refractory
      hypoxemia prone positioning should be attempted. The use of aerosolized pulmonary
      vasodilators can be used to buy time when these approaches fail as the patient is
      transitioned to extracorporeal membrane oxygenation. We also find that there is
      now sufficient evidence to recommend against the use of high frequency
      oscillation in the management of refractory hypoxemia. 

PMID- 23857447
TI  - Atropine for premedication: is no longer the time to be nostalgic.

PMID- 23857448
TI  - Comment to the editorial about patients with open abdomen.

PMID- 23857449
TI  - Do we need alternatives for bicarbonate and anion gap?

PMID- 23857450
TI  - A move in the right direction?

PMID- 23857451
TI  - A systems approach to the difficult airway extubation.

PMID- 23857452
TI  - Thoracic aortic mural thrombus as a cause of multiorgan failure.

PMID- 23857453
TI  - Prothymosin alpha protects cardiomyocytes against ischemia-induced apoptosis via
      preservation of Akt activation.
AB  - The human prothymosin alpha (PTalpha) gene encodes a 12.5 kDa highly acidic
      nuclear protein that is widely expressed in mammalian tissues including the heart
      and importantly, is detectable also in blood serum. During apoptosis or necrosis,
      PTalpha changes its nuclear localization and is able to exert an important
      cytoprotective effect. Since the role of PTalpha in the heart has never been
      evaluated, the aim of the present study was to investigate the effects of PTalpha
      on cardiomyocytes during ischemic injury. Our data show that seven after
      myocardial infarction (MI), PTalpha expression levels are significantly increased
      both in blood serum and in cardiac tissue, and notably we observe that PTalpha
      translocates from the nuclei to cytoplasm and plasma membrane of cardiomyocytes
      following MI. Furthermore, in vitro experiments in cardiomyocytes, confirm that
      after 6 h of simulated ischemia (SI), PTalpha protein levels are upregulated
      compared to normoxic cells. Importantly, treatment of cardiomyocytes with a
      recombinant PTalpha (rPTalpha), during SI results in a significant decrease in
      the apoptotic response and in a robust increase in cell survival. Moreover, these
      effects are accompanied to a significant preservation of the activated levels of
      the anti-apoptotic serine-threonine kinase Akt. Consistent with our in vitro
      observation, rPTalpha-treated MI mice exhibit a strong reduction in infarct size
      at 24 h, compared to the MI control group and at the molecular level, PTalpha
      treatment induces activation of Akt. The present study provides for the first
      time the demonstration that PTalpha offers cardioprotection against ischemic
      injury by an Akt-dependent mechanism. 

PMID- 23857454
TI  - Study of the enantioselective interaction of diclofop and human serum albumin by
      spectroscopic and molecular modeling approaches in vitro.
AB  - In this contribution, the enantioselective interactions between diclofop (DC) and
      human serum albumin (HSA) were explored by steady-state and 3D fluorescence,
      ultraviolet-visible spectroscopy (UV-vis), and molecular modeling. The binding
      constants between R-DC and HSA were 0.9213 * 10(5), 0.9118 * 10(5), and 0.9009 *
      10(5) L . mol(-1) at 293, 303, 313 K, respectively. Moreover, the binding
      constants of S-DC for HSA were 1.4766 * 10(5), 1.2899 * 10(5), and 1.0882 * 10(5)
      L . mol(-1) at 293, 303, and 313 K individually. Such consequences markedly
      implied the binding between DC enantiomers and HSA were enantioselective with
      higher affinity for S-DC. Steady-state fluorescence study evidenced the formation
      of DC-HSA complex and there was a single class of binding site on HSA. The
      thermodynamic parameters (DeltaH, DeltaS, DeltaG) of the reaction clearly
      indicated that hydrophobic effects and H-bonds contribute to the formation of DC
      HSA complex, which was in excellent agreement with molecular simulations. In
      addition, both site-competitive replacement and molecular modeling suggested that
      DC enantiomers were located within the binding pocket of Sudlow's site II.
      Furthermore, the alterations of HSA secondary structure in the presence of DC
      enantiomers were verified by UV-vis absorption and 3D fluorescence spectroscopy.
      This study can provide important insight into the enantioselective interaction of
      physiological protein HSA with chiral aryloxyphenoxy propionate herbicides and
      gives support to the use of HSA for chiral pesticides ecotoxicology and
      environmental risk assessment.

PMID- 23857455
TI  - The effect of bisphosphonate acidity on the activity of a thymidylyltransferase.
AB  - Thymidylyltransferases (thymidine diphospho pyrophosphorylases) are
      nucleotidylyltransferases that play key roles in the biosynthesis of carbohydrate
      components within bacterial cell walls and in the biosynthesis of glycosylated
      natural products. They catalyze the formation of sugar nucleotides concomitant
      with the release of pyrophosphate. Protein engineering of thymidylyltransferases
      has been an approach for the production of a variety of non-physiological sugar
      nucleotides. In this work, we have explored chemical approaches towards modifying
      the activity of the thymidylyltransferase (Cps2L) cloned from S. pneumoniae,
      through the use of chemically synthesized 'activated' nucleoside triphosphates
      with enhanced leaving groups, or by switching the metal ion co-factor
      specificity. Within a series of phosphonate-containing nucleoside triphosphate
      analogues, thymidylyltransferase activity is enhanced based on the acidity of the
      leaving group and a Bronsted-type analysis indicated that leaving group departure
      is rate limiting. We have also determined IC50 values for a series of
      bisphosphonates as inhibitors of thymidylyltransferases. No correlation between
      the acidity of the inhibitors (pKa) and the magnitude of enzyme inhibition was
      found. 

PMID- 23857456
TI  - Propofol for screening colonoscopy in low-risk patients: are we paying too much?

PMID- 23857457
TI  - Robustness of intratumour 18F-FDG PET uptake heterogeneity quantification for
      therapy response prediction in oesophageal carcinoma.
AB  - PURPOSE: Intratumour uptake heterogeneity in PET quantified in terms of textural
      features for response to therapy has been investigated in several studies,
      including assessment of their robustness for reconstruction and physiological
      reproducibility. However, there has been no thorough assessment of the potential
      impact of preprocessing steps on the resulting quantification and its predictive
      value. The goal of this work was to assess the robustness of PET heterogeneity in
      textural features for delineation of functional volumes and partial volume
      correction (PVC). METHODS: This retrospective analysis included 50 patients with
      oesophageal cancer. PVC of each PET image was performed. Tumour volumes were
      determined using fixed and adaptive thresholding, and the fuzzy locally adaptive
      Bayesian algorithm, and heterogeneity was quantified using local and regional
      textural features. Differences in the absolute values of the image-derived
      parameters considered were assessed using Bland-Altman analysis. The impact on
      their predictive value for the identification of patient nonresponders was
      assessed by comparing areas under the receiver operating characteristic curves.
      RESULTS: Heterogeneity parameters were more dependent on delineation than on PVC.
      The parameters most sensitive to delineation and PVC were regional ones
      (intensity variability and size zone variability), whereas local parameters such
      as entropy and homogeneity were the most robust. Despite the large differences in
      absolute values obtained from different delineation methods or after PVC, these
      differences did not necessarily translate into a significant impact on their
      predictive value. CONCLUSION: Parameters such as entropy, homogeneity,
      dissimilarity (for local heterogeneity characterization) and zone percentage (for
      regional characterization) should be preferred. This selection is based on a
      demonstrated high differentiation power in terms of predicting response, as well
      as a significant robustness with respect to the delineation method used and the
      partial volume effects.

PMID- 23857458
TI  - High 123I-MIBG uptake in neuroblastic tumours indicates unfavourable
      histopathology.
AB  - PURPOSE: Scintigraphy using (123)I-metaiodobenzylguanidine ((123)I-MIBG) is
      widely used for the detection of neuroblastic tumours. The aim of this study was
      to identify a possible correlation between the uptake intensity on (123)I-MIBG
      SPECT and histopathology of neuroblastic tumours. METHODS: (123)I-MIBG SPECT
      examinations were performed in 55 paediatric patients with neuroblastic tumour
      and compared to histopathology after surgical resection or biopsy at a mean of 2
      weeks after SPECT. For each lesion International Neuroblastoma Pathology
      Classification System (INPC) stage, mitosis karyorrhexis index (MKI), location
      and a semiquantitative tumour-to-liver count-rate ratio (TLCRR) were determined.
      Also, the presence or absence of MYCN amplification, p1 deletion, urine
      catecholamine and neuron-specific enolase blood levels at the time of scanning
      were recorded. RESULTS: In the 55 patients, 61 lesions were evaluated with (123)I
      MIBG SPECT and corresponding histopathological findings were reviewed (11
      ganglioneuroma, 11 ganglioneuroblastoma and 39 neuroblastoma). TLCRR was
      significantly higher in the neuroblastoma group (mean TLCRR 2.7) than in the
      ganglioneuroblastoma group (mean TLCRR 1.0) and ganglioneuroma group (mean TLCRR
      0.7) at the time of primary diagnosis (p < 0.001) and at follow-up (p = 0.039).
      Intense (123)I-MIBG uptake was found in tumour tissue with a high mitotic
      activity (MKI-high or MKI-intermediate) after treatment. Four ganglioneuromas (36
      %), three ganglioneuroblastomas (27 %) and six neuroblastomas (15 %) were (123)I
      MIBG-negative. CONCLUSION: In paediatric patients with peripheral neuroblastic
      tumours, strong (123)I-MIBG uptake indicates unfavourable histopathology. High
      uptake was seen in neuroblastomas and in tumours with a high mitotic activity.

PMID- 23857460
TI  - Gratifying clinical experience with an indigenously formulated single-vial
      lyophilized HYNIC-TOC kit at the radiopharmaceutical division of BARC: a pivotal
      boost for building up a peptide receptor radionuclide therapy programme in an
      Indian setting.

PMID- 23857459
TI  - Comparative study of the safety of regadenoson between patients with
      mild/moderate chronic obstructive pulmonary disease and asthma.
AB  - PURPOSE: To compare the safety of regadenoson, a selective agonist of A2A
      adenosine receptors, combined with low-level exercise, between subjects with
      mild/moderate chronic obstructive pulmonary disease (COPD) and asthma referred
      for myocardial perfusion imaging (MPI). METHODS: We studied 116 patients, of whom
      67 had COPD and 49 asthma (62 % men, mean age 68.3 +/- 11.3 years, range 31 - 87
      years). Patient demographics, past medical history, medications, clinical
      symptoms during stress and changes in blood pressure (BP) and heart rate (HR)
      were evaluated. RESULTS: Both groups were comparable with regard to hypertension,
      dyslipidaemia, diabetes and medications with the exception of a higher rate of
      use of anticholinergics in patients with COPD and of antileukotrienes in
      asthmatics (58.2 % vs. 28.6 % and 1.5 % vs. 14.3 %, respectively; all p < 0.01).
      There was a higher incidence of dyspnoea in COPD patients and of headache and
      feeling hot in asthmatic patients (40.3 % vs. 22.4 %, 6 % vs. 18.4 % and 10.4 %
      vs. 26.5 %, respectively; all p < 0.05). Although there was no difference in the
      incidence of other adverse events, we observed a higher frequency in asthmatics
      of flushing, dry mouth, sweating and fatigue (1.5 % vs. 6.1 %, 14.9 % vs. 24.5 %,
      0 % vs. 4.1 % and 37.3 % vs. 49 %, respectively). Adverse events were self
      limiting, except in three patients who suffered persistent dyspnoea (2 of 67 COPD
      patients; 1 of 49 asthma patients) requiring theophylline administration. We
      observed no significant changes in BP among either group, but there was a
      tendency towards a higher increase in systolic BP in COPD patients following
      regadenoson administration (148.3 +/- 27.6 vs. 154.6 +/- 31.0 mmHg, p = 0.056).
      CONCLUSION: This study showed a good safety profile in our series of COPD and
      asthma patients undergoing MPI. Regadenoson was well tolerated by all patients,
      with dyspnoea, headache and feeling hot showing differences between groups.

PMID- 23857461
TI  - Visualization of caspase-3-like activity in cells using a genetically encoded
      fluorescent biosensor activated by protein cleavage.
AB  - Cytosolic caspase-3-like proteases, such as caspase-3 and caspase-7, have a
      central role in mediating the progress of apoptosis. Here to conveniently monitor
      caspase-3-like activity in the multicellular environment, we have developed
      genetically encoded switch-on fluorescence-base indicators that are cyclized
      chimeras containing a caspase-3 cleavage site as a switch. When cleaved by
      caspase-3-like proteases, the non-fluorescent indicator rapidly becomes
      fluorescent, and thus detects in real-time the activation of such caspases. We
      generate cultured cells constitutively expressing these chimeras, and all the
      healthy cells are non-fluorescent. When these cells are exposed to apoptotic
      stimuli, dead cells show strong fluorescence depending on caspase activation.
      With these tools, we monitor in real-time caspase-3-like activity in each cell
      under various conditions, and show for the first time that the environment of
      cancer cells affects their sensitivity to chemotherapeutic drugs in a modified
      soft agar assay. These biosensors should enable better understanding of the
      biological relevance of caspase-3-like proteases. 

PMID- 23857464
TI  - Answer to the letter to the editor of A. Sotto et al. concerning "Antibiotic
      treatment in patients with chronic low back pain and vertebral bone edema (Modic
      type 1 changes): a double-blind randomized controlled trial of efficacy" by
      Albert HB et al., Eur Spine J (2013) 22:697-707.

PMID- 23857462
TI  - Cost effectiveness of romiplostim for the treatment of chronic immune
      thrombocytopenia in Ireland.
AB  - BACKGROUND: Romiplostim, a thrombopoietin receptor agonist (TPOra), is a second
      line medical treatment option for adults with chronic immune thrombocytopenia
      (ITP). Clinical trials have shown that romiplostim increases platelet counts,
      while reducing the risk of bleeding and, in turn, the need for costly rescue
      medications. AIMS: The objective of this study was to assess the cost
      effectiveness of romiplostim in the treatment of adult ITP in Ireland, in
      comparison with eltrombopag and the medical standard of care (SoC). METHODS: A
      lifetime treatment-sequence cost-utility Markov model with embedded decision tree
      was developed from an Irish healthcare perspective to compare romiplostim with
      eltrombopag and SoC. The model was driven by platelet response (platelet count
      >=50 * 10(9)/L), which determined effectiveness and progression along the
      treatment pathway, need for rescue therapy (e.g. intravenous immunoglobulin
      [IVIg] and steroids) and risk of bleeding. Probability of response, mean
      treatment duration, average time to initial response and utilities were derived
      from clinical trials and other published evidence. Treatment sequences and
      healthcare utilization practice were validated by Irish clinical experts. Costs
      were assessed in <euro> for 2011 and included drug acquisition costs and costs
      associated with monitoring patients and management of bleeding, as available from
      published Irish reimbursement lists and other relevant sources. Deterministic and
      probabilistic sensitivity analyses were conducted. RESULTS: Romiplostim treatment
      resulted in an average of 20.2 fewer administrations of rescue medication (IVIg
      or intravenous steroids) over a patient lifetime than eltrombopag, and 29.3 fewer
      rescue medication administrations than SoC. Romiplostim was dominant, with cost
      savings of <euro>13,258 and <euro>22,673 and gains of 0.76 and 1.17 quality
      adjusted life-years (QALYs), compared with eltrombopag and SoC, respectively.
      Romiplostim remained cost effective throughout a variety of potential scenarios,
      including short-term TPOra treatment duration (1 year). One-way sensitivity
      analysis showed that the model was most sensitive to variation in the cost of
      IVIg and use of romiplostim and IVIg. Probabilistic sensitivity analysis showed
      that romiplostim was likely to be cost effective in over 90 % of cases compared
      with eltrombopag, and 96 % compared with SoC at a willingness-to-pay threshold of
      <euro>30,000 per QALY. CONCLUSIONS: Use of romiplostim in the ITP treatment
      pathway, compared with eltrombopag or SoC, is likely to be cost effective in
      Ireland. Romiplostim improves clinical outcomes by increasing platelet counts,
      reducing bleeding events and the use of IVIg and steroids, resulting in both cost
      savings and additional QALYs when compared with current treatment practices.

PMID- 23857465
TI  - Answer to the Letter to the Editor of Benjamin John Floyd Dean et al. entitled
      "No conflict of interest?" concerning "Antibiotic treatment in patients with
      chronic low back pain and vertebral bone edema (Modic type 1 changes): a double
      blind randomized controlled trial of efficacy" by Albert HB et al., Eur Spine J
      (2013) 22:697-707.

PMID- 23857466
TI  - Answer to the Letter to the Editor of Benjamin John Floyd Dean entitled "Do these
      results apply to the 'intervention naive' patient?" concerning "Antibiotic
      treatment in patients with chronic low back pain and vertebral bone edema (Modic
      type 1 changes): a double-blind randomized controlled trial of efficacy" by
      Albert HB et al., Eur Spine J (2013) 22:697-707.

PMID- 23857467
TI  - A circuit of paracrine signals between liver sinusoid endothelial cells and
      hepatocytes regulates hepatitis C virus replication.

PMID- 23857468
TI  - Routine vaginal examinations for assessing progress of labour to improve outcomes
      for women and babies at term.
AB  - BACKGROUND: Vaginal examinations have become a routine intervention in labour as
      a means of assessing labour progress. Used at regular intervals, either alone or
      as a component of the partogram (a pre-printed form providing a pictorial
      overview of the progress of labour), the aim is to assess if labour is
      progressing physiologically, and to provide an early warning of slow progress.
      Abnormally slow progress can be a sign of labour dystocia, which is associated
      with maternal and fetal morbidity and mortality, particularly in low-income
      countries where appropriate interventions cannot easily be accessed. However,
      over-diagnosis of dystocia can lead to iatrogenic morbidity from unnecessary
      intervention (e.g. operative vaginal birth or caesarean section). It is,
      therefore, important to establish whether or not the routine use of vaginal
      examinations is an effective intervention, both as a diagnostic tool for true
      labour dystocia, and as an accurate measure of physiological labour progress.
      OBJECTIVES: To compare the effectiveness, acceptability and consequences of
      digital vaginal examination(s) (alone or within the context of the partogram)
      with other strategies, or different timings, to assess progress during labour at
      term. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's
      Trials Register (28 February 2013) and reference lists of identified studies.
      SELECTION CRITERIA: We included randomised controlled trials (RCTs) of vaginal
      examinations (including digital assessment of the consistency of the cervix, and
      the degree of dilation and position of the opening of the uterus (cervical os);
      and position and station of the fetal presenting part, with or without abdominal
      palpation) compared with other ways of assessing progress of labour. We also
      included studies assessing different timings of vaginal examinations. We excluded
      quasi-RCTs and cross-over trials. We also excluded trials with a primary focus on
      assessing progress of labour using the partogram (of which vaginal examinations
      is one component) as this is covered by another Cochrane review. However, studies
      where vaginal examinations were used within the context of the partogram were
      included if the studies were randomised according to the vaginal examination
      component. DATA COLLECTION AND ANALYSIS: Three review authors assessed the
      studies for inclusion in the review. Two authors undertook independent data
      extraction and assessed the risk of bias of each included study. A third review
      author also checked data extraction and risk of bias. Data entry was checked.
      MAIN RESULTS: We found two studies that met our inclusion criteria but they were
      of unclear quality. One study, involving 307 women, compared vaginal examinations
      with rectal examinations, and the other study, involving 150 women, compared two
      hourly with four-hourly vaginal examinations. Both studies were of unclear
      quality in terms of risk of selection bias, and the study comparing the timing of
      the vaginal examinations excluded 27% (two hourly) to 28% (four hourly) of women
      after randomisation because they no longer met the inclusion criteria.When
      comparing routine vaginal examinations with routine rectal examinations to assess
      the progress of labour, we identified no difference in neonatal infections
      requiring antibiotics (risk ratio (RR) 0.33, 95% confidence interval (CI) 0.01 to
      8.07, one study, 307 infants). There were no data on the other primary outcomes
      of length of labour, maternal infections requiring antibiotics and women's
      overall views of labour. The study did show that significantly fewer women
      reported that vaginal examination was very uncomfortable compared with rectal
      examinations (RR 0.42, 95% CI 0.25 to 0.70, one study, 303 women). We identified
      no difference in the secondary outcomes of augmentation, caesarean section,
      spontaneous vaginal birth, operative vaginal birth, perinatal mortality and
      admission to neonatal intensive care.Comparing two-hourly vaginal examinations
      with four-hourly vaginal examinations in labour, we found no difference in length
      of labour (mean difference in minutes (MD) -6.00, 95% CI -88.70 to 76.70, one
      study, 109 women). There were no data on the other primary outcomes of maternal
      or neonatal infections requiring antibiotics, and women's overall views of
      labour. We identified no difference in the secondary outcomes of augmentation,
      epidural for pain relief, caesarean section, spontaneous vaginal birth and
      operative vaginal birth. AUTHORS' CONCLUSIONS: On the basis of women's
      preferences, vaginal examination seems to be preferred to rectal examination. For
      all other outcomes, we found no evidence to support or reject the use of routine
      vaginal examinations in labour to improve outcomes for women and babies. The two
      studies included in the review were both small, and carried out in high-income
      countries in the 1990s.  It is surprising that there is such a widespread use of
      this intervention without good evidence of effectiveness, particularly
      considering the sensitivity of the procedure for the women receiving it, and the
      potential for adverse consequences in some settings.The effectiveness of the use
      and timing of routine vaginal examinations in labour, and other ways of assessing
      progress in labour, including maternal behavioural cues, should be the focus of
      new research as a matter of urgency. Women's views of ways of assessing labour
      progress should be given high priority in any future research in this area.

PMID- 23857469
TI  - Static coatings for the analysis of intact monoclonal antibody drugs by capillary
      zone electrophoresis.
AB  - This work reports on the investigation of the optimal conditions associated with
      good isoform resolution, minimized adsorption, and acceptable repeatability for
      the analysis of intact monoclonal antibodies. To this end, various static
      capillary coatings were evaluated, and major trends were observed. For a
      positively charged coating, a low EOF mobility value was the main criterion for
      satisfactory resolution. For neutral coatings, adsorption was the main concern.
      If the coating does not fully cover the surface silanols, electrostatic
      interactions tend to decrease protein recovery through irreversible adsorption.
      The influence of the BGE pH was also investigated, as the resolution of
      monoclonal antibody isoforms is driven by their charge difference. The nature and
      concentration of the BGE were proven to be important, as an ampholytic compound
      such as epsilon-aminocaproic acid was found to decrease adsorption compared with
      ammonium acetate. With the optimal conditions determined during method
      development, a complete investigation according to four criteria, i.e. migration
      time, separation efficiency, EOF mobility, and protein recovery, did not present
      evidence of any adsorption. Finally, the repeatability and intermediate precision
      were assessed, and low variability was demonstrated with an RSD less than 1.3%
      for the main peak migration time. 

PMID- 23857470
TI  - Diversity in the complexity of phosphate starvation transcriptomes among rice
      cultivars based on RNA-Seq profiles.
AB  - Rice has developed several morphological and physiological strategies to adapt to
      phosphate starvation in the soil. In order to elucidate the molecular basis of
      response to phosphate starvation, we performed mRNA sequencing of 4 rice
      cultivars with variation in growth response to Pi starvation as indicated by the
      shoot/root dry weight ratio. Approximately 254 million sequence reads were mapped
      onto the IRGSP-1.0 reference rice genome sequence and an average of about 5,000
      transcripts from each cultivar were found to be responsive under phosphate
      starvation. Comparative analysis of the RNA-Seq profiles of the 4 cultivars
      revealed similarities as well as distinct differences in expression of these
      responsive transcripts. We elucidated a set of core responsive transcripts
      including annotated and unannotated transcripts commonly expressed in the 4
      cultivars but with different levels of expression. De novo assembly of unmapped
      reads to the Nipponbare genome generated a set of sequence contigs representing
      potential new transcripts that may be involved in tolerance to phosphate
      starvation. This study can be used for identification of genes and gene networks
      associated with environmental stress and the development of novel strategies for
      improving tolerance to phosphate starvation in rice and other cereal crops. 

PMID- 23857472
TI  - Relapses of thrombotic thrombocytopenic purpura after treatment with rituximab.
AB  - Rituximab has been added to therapeutic plasma exchange (TPE) in the last 10
      years for refractory thrombotic thrombocytopenic purpura (TTP). We performed a
      retrospective single institution study to determine if patients with TTP treated
      with TPE and rituximab experienced relapses. We reviewed the electronic and
      apheresis records of patients treated between 2003 and 2008 and collected the
      following parameters: demographics, laboratory results, treatment
      characteristics, and follow-up. We identified 12 patients with ADAMTS13 <5% due
      to an inhibitor who received TPE and rituximab during the study period. The mean
      number of TPEs required to achieve remission was 24 +/- 3, time to remission was
      28 +/- 3 days, and hospital length of stay was 36 +/- 4 days. During a mean
      follow-up of 73.4 +/- 6 months, four patients (33%) relapsed. On average, relapse
      occurred at 62 +/- 8.5 months postachievement of remission. The one-year, three
      year, and five-year relapse free-survival (RFS) rates were 92%, 75%, and 75%,
      respectively. On multivariate analysis, we failed to identify independent
      predictors of relapse. This retrospective analysis does not support the notion
      that rituximab prevents or decreases the rate of relapse in TTP. Prospective
      randomized studies are needed to confirm this observation.

PMID- 23857471
TI  - Populus euphratica: the transcriptomic response to drought stress.
AB  - Populus euphratica Olivier is widely established in arid and semiarid regions but
      lags in the availability of transcriptomic resources in response to water
      deficiency. To investigate the mechanisms that allow P. euphratica to maintain
      growth in arid regions, the responses of the plant to soil water deficit were
      analyzed at a systems level using physiological and pyrosequencing approaches. We
      generated 218,601 and 287,120 reads from non-stressed control and drought
      stressed P. euphratica leaves respectively, totaling over 200 million base pairs.
      After assembly, 24,013 transcripts were yielded with an average length of 1,128
      bp. We determined 2,279 simple sequence repeats, which may have possible
      information for understanding drought adaption of woody plants. Stomatal closure
      was inhibited under moderate drought to maintain a relatively high rate of CO2
      assimilation and water transportation, which was supposed to be important for P.
      euphratica to maintain normal growth and develop vigorous root systems in an
      adverse environment. This was accompanied by strong transcriptional remodeling of
      stress-perception, signaling and transcription regulation, photoprotective
      system, oxidative stress detoxification, and other stress responsive genes. In
      addition, genes involved in stomatal closure inhibition, ascorbate-glutathione
      pathway and ubiquitin-proteasome system that may specially modulate the drought
      stress responses of P. euphratica are highlighted. Our analysis provides a
      comprehensive picture of how P. euphratica responds to drought stress at
      physiological and transcriptome levels which may help to understand molecular
      mechanisms associated with drought response and could be useful for genetic
      engineering of woody plants. 

PMID- 23857473
TI  - CAPE promotes TRAIL-induced apoptosis through the upregulation of TRAIL receptors
      via activation of p38 and suppression of JNK in SK-Hep1 hepatocellular carcinoma
      cells.
AB  - Caffeic acid phenethyl ester (CAPE), a phenolic compound derived from honeybee
      propolis, has been reported to possess anticancer activities in several types of
      malignant cells. Here, we show that treatment with tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) in combination with CAPE significantly
      sensitized SK-Hep1 cells to TRAIL-induced apoptosis. The sensitization to TRAIL
      was accompanied by the activation of extrinsic and intrinsic apoptotic pathways,
      leading to the activation of caspases, mitochondrial disruption and PARP
      cleavage. Moreover, TRAIL receptors, such as DR4 and DR5 were significantly
      upregulated by CAPE treatment, and both DR4/Fc and DR5/Fc chimera markedly
      abrogated apoptosis induced by CAPE and TRAIL, demonstrating the critical role of
      these death receptors in combination-induced apoptosis. The effect of CAPE on
      mitogen-activated protein kinases (MAPKs) was further examined, where CAPE
      treatment resulted in the activation of p38 and the inhibition of JNK, without
      affecting levels of phospho-ERK. Our results showed that p38 and JNK exhibited
      the opposite role in SK-Hep1 cells. The inhibition of p38, using SB203580,
      blocked the CAPE-induced expression of death receptors and attenuated the
      combination-induced apoptosis, suggesting the pro-apoptotic role of p38. In
      contrast, JNK-specific inhibition, by SP600125, triggered upregulation of DR4 and
      DR5, and sensitized SK-Hep1 cells to TRAIL, indicating that the CAPE-induced
      suppression of JNK may contribute to the sensitizing effect of CAPE through the
      upregulation of death receptors. Taken together, these results indicate that CAPE
      potentiated TRAIL-induced apoptosis in SK-Hep1 cells, through upregulation of
      TRAIL receptors via modulation of p38 and JNK signaling pathways. 

PMID- 23857474
TI  - Voltammetric behaviour of free DNA bases, methylcytosine and oligonucleotides at
      disposable screen printed graphite electrode platforms.
AB  - Improvements in analytical methods for the determination and quantification of
      methylcytosine in DNA are vital since it has the potential to be used as a
      biomarker to detect different diseases in the first stage such as in the case of
      carcinomas and sterility. In this work we utilized screen printed graphite
      electrodes (SPGE) for studying the electrochemical response of all free DNA
      bases, methylcytosine and short oligonucleotides by cyclic voltammetry (CV) and
      square wave voltammetry (SWV). CV and SWV responses of free DNA bases and
      methylcytosine have been investigated by using SPGE platforms and the feasibility
      of detecting and quantifying cytosine and methylcytosine as free DNA moieties has
      been evaluated as a function of pH, concentration and the presence of the other
      free DNA bases in solution simultaneously. Repeatability of using SWV has been
      performed for the electrochemical behavior of both 250 MUM cytosine and 250 MUM
      methylcytosine in the presence of 25 MUM guanine, with coefficient of variations
      of 6.9% and 2.6% respectively based upon peak current (N = 5). Six-mer
      oligonucleotides with a sequence 5'-XXXCGC-3', where the XXX motif corresponds to
      TTT, TTA, TAA and AAA have been performed using SWV in 0.1 M acetate buffer pH
      5.0 to explore how the DNA base position effects the electrooxidation of guanine
      and cytosine into the oligonucleotide. Furthermore SWV comparisons of the
      electrooxidation of the oligonucleotides 5'-CGCGCG-3' and its methylated 5'
      mCGmCGmCG-3' have been performed with concentrations in acetate buffer solutions,
      and the interaction of both oligonucleotides with the graphitic surface of the
      SPGE has been demonstrated by fitting well-known adsorption models such as
      Freundlich and Langmuir kinetics according to the SWV current response of
      guanine, cytosine and methylcytosine into the oligonucleotide. 

PMID- 23857475
TI  - Clinical and economic burden of emergency department visits due to
      gastrointestinal diseases in the United States.
AB  - OBJECTIVES: Gastrointestinal (GI) emergencies may cause substantial morbidity.
      Our aims were to characterize the national clinical and economic burden of GI
      visits to emergency departments (EDs) in the United States. METHODS: We performed
      an observational cross-sectional study using the 2007 Nationwide Emergency
      Department Sample, the largest US all-payer ED database, to identify the leading
      causes for ED visits due to GI diseases and their associated charges, stratified
      by age and sex. Logistic regression was used to analyze predictors of
      hospitalization after an ED visit. RESULTS: Of the 122 million ED visits in 2007,
      15 million (12%) had a primary GI diagnosis. The leading primary GI diagnoses
      were abdominal pain (4.7 million visits), nausea and vomiting (1.6 million
      visits), and functional disorders of the digestive system (0.7 million visits).
      The leading diagnoses differed by age group. The fraction of ED visits resulting
      in hospitalization was 21.6% for primary GI diagnoses vs. 14.7% for non-GI
      visits. Women had more ED visits with a primary GI diagnosis than men (58.5 (95%
      CI 56.0-60.9) vs. 41.6 (95% CI 39.8-43.3) per 1000 persons), but lower rates of
      subsequent hospitalization (20.0% (95% CI 19.4-20.7%) vs. 24.0% (95% CI 23.3
      24.6%)). There were no differences in hospitalization rates between sexes after
      adjustment by age, primary GI diagnosis, and Charlson Comorbidity Score. The
      total charges for ED visits with a primary GI diagnosis in 2007 were $27.9
      billion. CONCLUSIONS: GI illnesses account for substantial clinical and economic
      burdens on US emergency medical services.

PMID- 23857476
TI  - Duration of anticoagulation for the management of venous thromboembolism in
      inflammatory bowel disease: a decision analysis.
AB  - OBJECTIVES: There is practice variation in the duration of anticoagulation for
      venous thromboembolism (VTE) in inflammatory bowel disease (IBD) patients.
      Clinicians must weigh the high risk of recurrent VTE with the risk of
      gastrointestinal bleeding. METHODS: We implemented Markov decision analysis to
      compare the costs and effectiveness of extended anticoagulation vs. time-limited
      anticoagulation (6 months) among IBD patients with first unprovoked VTE over a 5
      year time horizon. In a secondary analysis, we added two strategies in which
      therapeutic-dose or prophylactic-dose anticoagulation was administered during IBD
      flares. RESULTS: Compared with time-limited anticoagulation, extended
      anticoagulation yielded slightly higher quality-adjusted life years (QALYs) (4.40
      vs. 4.38) and costs ($21,158 vs. $20,825), and an incremental cost-effectiveness
      ratio (ICER) of $15,254/QALY over 5 years. In secondary analysis, pharmacological
      prophylaxis during IBD flares was associated with the highest QALYs (4.41) and
      costs ($28,177), but was not cost-effective when compared with extended
      anticoagulation (ICER=$1,158,717/QALY). Anticoagulation during flares yielded the
      lowest cost ($19,681) and same QALYs as extended anticoagulation. In
      probabilistic sensitivity analysis, extended anticoagulation yielded higher QALYs
      than time-limited anticoagulation in 91% of trials and was dominant or cost
      effective (<$50,000/QALY) in 72% of trials. When analyzed over a lifetime,
      extended anticoagulation dominated time-limited anticoagulation with higher
      effectiveness (18.44 vs. 17.95 QALYs) and lower costs ($94,738 vs. $102,874) and
      was highly robust in sensitivity analyses. CONCLUSIONS: Our analyses suggest that
      extended anticoagulation may provide marginal benefit over time-limited
      anticoagulation and should be considered in the management of first unprovoked
      VTE in IBD. Anticoagulation and prophylaxis during IBD flares are alternative
      viable strategies.

PMID- 23857477
TI  - Oral bisphosphonates and the risk of Barrett's esophagus: case-control analysis
      of US veterans.
AB  - OBJECTIVES: This study examined Barrett's esophagus (BE) risk factors in veterans
      to determine the association between risk of BE and use of oral bisphosphonates.
      METHODS: We conducted a case-control study among eligible patients scheduled for
      an elective esophagogastroduodenoscopy (EGD) and a sample of patients eligible
      for screening colonoscopy recruited from primary care clinics from a single VA
      Medical Center. Cases with definitive BE were compared with controls; all
      underwent study EGD. Use of oral bisphosphonates was ascertained by reviewing
      filled prescriptions in electronic pharmacy records. We calculated odds ratios
      (ORs) and 95% confidence intervals (95% CIs), using multivariate logistic
      regression modeling while adjusting for sex, age, race, proton-pump inhibitor
      use, hiatal hernia, waist-to-hip ratio, Helicobacter pylori infection, and
      gastroesophageal reflux disorder (GERD) symptoms. RESULTS: There were 285 BE
      cases, 1,122 endoscopy controls, and 496 primary care controls. Alendronate and
      risedronate were the only oral bisphosphonates prescribed. The proportion of BE
      cases with filled prescription of oral bisphosphonates (4.6%) was greater than in
      endoscopy controls (1.6%) or primary care controls (2.9%). In the adjusted
      analysis, oral bisphosphonate use was significantly associated with BE risk
      (OR=2.33; 95% CI: 1.11-4.88) compared with the combined control groups. This
      association remained significant when BE cases were compared with endoscopy
      controls only (OR=2.74; 95% CI: 1.28-5.87) but was attenuated when compared with
      primary care controls only (OR=2.60; 95% CI: 0.99-6.84). The association was
      observed in patients with GERD symptoms (OR=3.29; 95% CI: 1.36-7.97) but not in
      those without GERD symptoms. CONCLUSION: Oral bisphosphonate use may increase the
      risk for BE, especially among patients with GERD.

PMID- 23857479
TI  - Spectral tuning of the n-UV convertible oxynitride phosphor: orange color
      emitting realization via an energy transfer mechanism.
AB  - Near-UV convertible Eu(3+)-activated orange oxynitride phosphors have been
      obtained via a Ce(3+)-> Tb(3+)-> Eu(3+) energy transfer mechanism. The Tb(3+)
      ions play the role of an energy transfer bridge to connect the Ce(3+) and Eu(3+)
      ion pairs, and an optimal concentration of the Tb(3+) ion is necessary for
      maximum intensity of the Eu(3+) ion emission. 

PMID- 23857478
TI  - Safety of endoscopic mucosal resection for Barrett's esophagus.
AB  - OBJECTIVES: Endoscopic mucosal resection (EMR) is an established technique for
      the management of Barrett's esophagus (BE). Although EMR is generally perceived
      to be a relatively safe procedure, the published data regarding EMR-related
      complications are variable and the expertise of those performing EMR is often not
      disclosed. Our aim was to determine the complication rates in a large cohort of
      patients who underwent EMR at a specialized BE unit. METHODS: A prospectively
      maintained database was reviewed for patients with BE who underwent EMR from
      January 1995 to August 2008. EMR was performed in patients with neoplastic
      appearing lesions. Bleeding, stricture, and perforation related to EMR were
      reviewed as the main outcome measurements. RESULTS: In all, 681 patients (83%
      male; mean age 70 years old) underwent a total of 1,388 endoscopic procedures and
      2,513 EMRs. Median length of BE was 3.0 cm (interquartile range (IQR) 1-7). A
      single experienced endoscopist performed 99% of the EMR procedures. EMR was
      performed using commercially available EMR kits in 95% (77% cap-snare and 18%
      band-snare) and a variceal band ligation device in 5% of cases. No EMR-related
      perforations occurred during the study period. The rate of post-EMR bleeding was
      1.2% (8 patients). Seven patients were successfully treated endoscopically and
      one needed surgery. The rate for symptomatic strictures after EMR was 1.0% (7
      cases), and all of the cases did not involve intervening ablation therapies. All
      strictures were successfully treated with endoscopic dilation. CONCLUSIONS: This
      is the largest series reported to date on EMR in BE. In this large retrospective
      study, EMR for BE was associated with a low rate of complications for selected
      patients when performed by experienced hands.

PMID- 23857480
TI  - Withholding CPR: a matter of policy?

PMID- 23857483
TI  - When is it safe to say "I'm sorry"?

PMID- 23857484
TI  - World Kidney Day: reaching out to the community.

PMID- 23857485
TI  - Change-of-shift report: from hallways to the bedside.

PMID- 23857486
TI  - Monomorphic ventricular tachycardia.

PMID- 23857489
TI  - Easing the burden on family caregivers.

PMID- 23857490
TI  - Patient education series. Deep vein thrombosis.

PMID- 23857492
TI  - Small things.

PMID- 23857493
TI  - Stepping up to be a nurse expert witness.

PMID- 23857494
TI  - Students promoting healthcare practices in Belize.

PMID- 23857495
TI  - How nurses can encourage shared decision making.

PMID- 23857496
TI  - Drugs for treating hypertension.

PMID- 23857499
TI  - Seismic Evidence for a Geosuture between the Yangtze and Cathaysia Blocks, South
      China.
AB  - South China, composed of the Yangtze and Cathaysia Blocks and the intervening
      Jiangnan orogenic belt, has been central to the debate on the tectonic evolution
      of East Asia. Here we investigate the crustal structure and composition of South
      China from seismic data employing the H-k stacking technique. Our results show
      that the composition and seismic structure of the crust in the Jiangnan orogenic
      belt are identical to those of the Cathaysia Block. Our data reveal a distinct
      contrast in the crustal structure and composition between the two flanks of the
      Jiujiang-Shitai buried fault. We propose that the Jiujiang-Shitai buried fault
      defines a geosuture between the Yangtze and Cathaysia Blocks, and that the felsic
      lower crust of the Cathaysia Block and the Jiangnan orogenic belt may represent
      fragments derived from the Gondwana supercontinent. 

PMID- 23857500
TI  - Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7
      through GSK3beta/beta-catenin pathway.
AB  - Recently, tumor initiating cells are considered as the central role of
      tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic
      lidamycin with great potential antitumor activity is currently evaluated in Phase
      II clinical trials. In this study, we evaluated the effect of lidamycin on tumor
      initiating cells of hepatocellular carcinoma Huh7 and identified the potential
      mechanism. Flow cytometry analysis and sorting assay, surface marker assay,
      sphere formation assay, and aldefluor assay were used to evaluate the effect of
      lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential
      mechanism, the activity of GSK3beta/beta-catenin pathway was detected by Western
      blot and T cell factors transcriptional activity assay. Subcutaneous tumor model
      in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells.
      Lidamycin decreased the proportion of EpCAM+ cells and the expression of EpCAM
      protein. Lidamycin inhibited sphere formation of sorted EpCAM+ cells in 7 d, and
      of parental cells in three serial passages. The population of aldehyde
      dehydrogenase-positive cells was reduced by lidamycin. In addition, lidamycin
      restrained tumor volume and incidence in vivo. Lidamycin activated GSK3beta, and
      degraded the activity of beta-catenin. Consequently, transcriptional activity of
      beta-catenin/T cell factors was decreased. In brief, these results suggest that
      lidamycin suppressed Huh7 tumor initiating cells via GSK3beta/beta-catenin
      pathway. These findings reveal the potential mechanism of lidamycin on tumor
      initiating cells and the benefit for further clinical evaluation.

PMID- 23857501
TI  - Improving palm oil quality through identification and mapping of the lipase gene
      causing oil deterioration.
AB  - The oil palm fruit mesocarp contains high lipase activity that increases free
      fatty acids and necessitates post-harvest inactivation by heat treatment of fruit
      bunches. Even before heat treatment the mesocarp lipase activity causes
      consequential oil losses and requires costly measures to limit free fatty acids
      quantities. Here we demonstrate that elite low-lipase lines yield oil with
      substantially less free fatty acids than standard genotypes, allowing more
      flexibility for post-harvest fruit processing and extended ripening for increased
      yields. We identify the lipase and its gene cosegregates with the low-/high
      lipase trait, providing breeders a marker to rapidly identify potent elite
      genitors and introgress the trait into major cultivars. Overall, economic gains
      brought by wide adoption of this material could represent up to one billion
      dollars per year. Expected benefits concern all planters but are likely to be
      highest for African smallholders who would be more able to produce oil that meets
      international quality standards. 

PMID- 23857502
TI  - Exosomes: a new weapon to treat the central nervous system.
AB  - The potential of exosomes to treat central nervous system (CNS) pathologies has
      been recently demonstrated. These studies make way for a complete new field that
      aims to exploit the natural characteristics of these vesicles, considered for a
      long time as side products of physiological cellular pathways. Recently, however,
      the biological significance of exosomes has been evaluated and exosomes can now
      be viewed upon as new relevant functional entities for development of novel
      therapeutic strategies. In this review, we aim to summarize the state-of-the-art
      role of exosomes in the CNS and to speculate about possible future therapeutic
      applications of exosomes. In particular, we will speculate about the use of these
      vesicles as a substitute of cell-based therapies for the treatment of brain
      damage and review the potential of exosomes as drug delivery vehicles for the
      CNS. 

PMID- 23857503
TI  - Rapid bacterial whole-genome sequencing to enhance diagnostic and public health
      microbiology.
AB  - IMPORTANCE: The latest generation of benchtop DNA sequencing platforms can
      provide an accurate whole-genome sequence (WGS) for a broad range of bacteria in
      less than a day. These could be used to more effectively contain the spread of
      multidrug-resistant pathogens. OBJECTIVE: To compare WGS with standard clinical
      microbiology practice for the investigation of nosocomial outbreaks caused by
      multidrug-resistant bacteria, the identification of genetic determinants of
      antimicrobial resistance, and typing of other clinically important pathogens.
      DESIGN, SETTING, AND PARTICIPANTS: A laboratory-based study of hospital
      inpatients with a range of bacterial infections at Cambridge University Hospitals
      NHS Foundation Trust, a secondary and tertiary referral center in England,
      comparing WGS with standard diagnostic microbiology using stored bacterial
      isolates and clinical information. MAIN OUTCOMES AND MEASURES: Specimens were
      taken and processed as part of routine clinical care, and cultured isolates
      stored and referred for additional reference laboratory testing as necessary.
      Isolates underwent DNA extraction and library preparation prior to sequencing on
      the Illumina MiSeq platform. Bioinformatic analyses were performed by persons
      blinded to the clinical, epidemiologic, and antimicrobial susceptibility data.
      RESULTS: We investigated 2 putative nosocomial outbreaks, one caused by
      vancomycin-resistant Enterococcus faecium and the other by carbapenem-resistant
      Enterobacter cloacae; WGS accurately discriminated between outbreak and
      nonoutbreak isolates and was superior to conventional typing methods. We compared
      WGS with standard methods for the identification of the mechanism of carbapenem
      resistance in a range of gram-negative bacteria (Acinetobacter baumannii, E
      cloacae, Escherichia coli, and Klebsiella pneumoniae). This demonstrated
      concordance between phenotypic and genotypic results, and the ability to
      determine whether resistance was attributable to the presence of carbapenemases
      or other resistance mechanisms. Whole-genome sequencing was used to recapitulate
      reference laboratory typing of clinical isolates of Neisseria meningitidis and to
      provide extended phylogenetic analyses of these. CONCLUSIONS AND RELEVANCE: The
      speed, accuracy, and depth of information provided by WGS platforms to confirm or
      refute outbreaks in hospitals and the community, and to accurately define
      transmission of multidrug-resistant and other organisms, represents an important
      advance.

PMID- 23857505
TI  - Detection of small (<=2 cm) HCC in cirrhotic patients: added value of diffusion
      MR-imaging.
AB  - OBJECTIVES: To evaluate the usefulness of the diffusion-weighted sequence in the
      detection of small (<=2 cm) hepatocellular carcinoma (HCC) in patients with
      cirrhosis. METHODS: Seventy cirrhotic patients with 93 HCCs underwent MR-Imaging
      at 1.5 T. MR acquisitions comprised unenhanced T1- and T2-weighted images and
      post-contrast Gd-BOPTA-enhanced T1W GRE-3D images acquired after approximately
      25, 60, 180 s (dynamic phases) and 90 min (hepatobiliary phase). DWI was
      performed by a SSEPI sequence (b values 0, 50, 400, 800 s/mm(2)). Quantitative
      analysis was performed to establish significant difference of ADC values of
      benign lesions compared with that of HCC. Sensitivity, specificity, positive and
      negative predictive values and diagnostic accuracy of two different protocols
      with and without diffusion MRI sequence were also calculated and compared each
      other. RESULTS: A good inverse correlation was found between reference standard
      and ADC values (rho = -0.688). The mean ADC value of HCC was significantly lower
      than the mean value of benign focal liver lesions (p < 0.0001). No significant
      difference was reported in term of sensitivity, specificity, PPV, NPV and
      diagnostic accuracy between the two datasets. A trend to a better sensitivity was
      found when DWI images were considered. CONCLUSIONS: The adjunction of DWI does
      not significantly improve the diagnostic accuracy in the detection of small HCC.

PMID- 23857504
TI  - The effects of MyD88 deficiency on disease phenotype in dysferlin-deficient A/J
      mice: role of endogenous TLR ligands.
AB  - An absence of dysferlin leads to activation of innate immune receptors such as
      Toll-like receptors (TLRs) and skeletal muscle inflammation. Myeloid
      differentiation primary response gene 88 (MyD88) is a key mediator of TLR
      dependent innate immune signalling. We hypothesized that endogenous TLR ligands
      released from the leaking dysferlin-deficient muscle fibres engage TLRs on muscle
      and immune cells and contribute to disease progression. To test this hypothesis,
      we generated and characterized dysferlin and MyD88 double-deficient mice. Double
      deficient mice exhibited improved body weight, grip strength, and maximum muscle
      contractile force at 6-8 months of age when compared to MyD88-sufficient,
      dysferlin-deficient A/J mice. Double-deficient mice also showed a decrease in
      total fibre number, which contributed to the observed increase in the number of
      central nuclei/fibres. These results indicate that there was less regeneration in
      the double-deficient mice. We next tested the hypothesis that endogenous ligands,
      such as single-stranded ribonucleic acids (ssRNAs), released from damaged muscle
      cells bind to TLR-7/8 and perpetuate the disease progression. We found that
      injection of ssRNA into the skeletal muscle of pre-symptomatic mice (2 months
      old) resulted in a significant increase in degenerative fibres, inflammation, and
      regenerating fibres in A/J mice. In contrast, characteristic histological
      features were significantly decreased in double-deficient mice. These data point
      to a clear role for the TLR pathway in the pathogenesis of dysferlin deficiency
      and suggest that TLR-7/8 antagonists may have therapeutic value in this disease.

PMID- 23857506
TI  - Complete genome sequence of Habenaria mosaic virus, a new potyvirus infecting a
      terrestrial orchid (Habenaria radiata) in Japan.
AB  - The complete genomic sequence of Habenaria mosaic virus (HaMV), which infects
      terrestrial orchids (Habenaria radiata), has been determined. The genome is
      composed of 9,499 nucleotides excluding the 3'-terminal poly(A) tail, encoding a
      large polyprotein of 3,054 amino acids with the genomic features typical of a
      potyvirus. Putative proteolytic cleavage sites were identified by sequence
      comparison to those of known potyviruses. The HaMV polyprotein showed 58 % amino
      acid sequence identity to that encoded by the most closely related potyvirus,
      tobacco vein banding mosaic virus. Phylogenetic analysis of the polyprotein amino
      acid sequence and its coding sequences confirmed that HaMV formed a cluster with
      the chilli veinal mottle virus group, most of which infect solanaceous plants.
      These results suggest that HaMV is a distinct member of the genus Potyvirus. 

PMID- 23857507
TI  - Telbivudine and adefovir combination therapy for patients with chronic lamivudine
      resistant hepatitis B virus infections.
AB  - We evaluated second-line salvage therapy with adefovir + telbivudine (group 1),
      adefovir followed by adefovir + telbivudine (group 2), or lamivudine + adefovir
      followed by adefovir + telbivudine (group 3) in hepatitis B patients with an
      inadequate virologic response to lamivudine treatment. Simple linear regression
      analysis showed that for each additional month of treatment, the most significant
      reduction in viral load occurred in group 1 (HBV DNA [Log10 IU/mL]: group 1, 
      0.149; group 2, -0.081; group 3, -0.123). Generalized estimating equation
      analysis revealed that compared to group 1, hepatitis B virus (HBV) DNA levels
      were 1.203 and 0.443 Log10 IU/mL higher in groups 2 and 3, respectively. Overall,
      a significant reduction in viral load (-0.060 Log10 IU/mL) was observed for each
      additional month of treatment. Adefovir + telbivudine treatment resulted in a
      significant reduction in HBV DNA levels. Moreover, telbivudine treatment resulted
      in a significant reduction in viral load (-0.050 Log10 IU/mL) compared to
      lamivudine treatment after the emergence of lamivudine resistance. 

PMID- 23857508
TI  - miR-125b inhibitor may enhance the invasion-prevention activity of temozolomide
      in glioblastoma stem cells by targeting PIAS3.
AB  - BACKGROUND: Temozolomide, an alkylating agent, is a promising chemotherapeutic
      agent for treating glioblastoma. Although chemotherapy with temozolomide may
      restrain tumor growth for some months, invariable tumor recurrence suggests that
      cancer stem cells maintaining these tumors persist. Previous research has shown
      that temozolomide can inhibit the proliferation of human glioblastoma stem cells
      (GSCs); however, no research has focused on the invasion of GSCs, which is an
      important factor for glioblastoma recurrence. Accumulating evidence indicates
      that microRNA (miR)-125b over-expression in GSCs may increase their invasiveness.
      OBJECTIVE: Our objective was to identify the effects and mechanism of action of
      an miR-125b inhibitor combined with temozolomide in the invasive pathogenesis of
      GSCs. METHODS: We modified the levels of miR-125b expression in primary GSCs in
      order to observe the effect on sensitivity to temozolomide on invasion, and we
      further analyzed the differences in mechanism between miR-125b treatment alone
      and treatment with miR-125b plus temozolomide using the Cancer PathwayFinder PCR
      Array. RESULTS: Our results demonstrated that either an miR-125b inhibitor or
      temozolomide could modestly inhibit the invasiveness of GSCs. Furthermore, GSCs
      that were pre-transfected with an miR-125b inhibitor, then treated with
      temozolomide, showed significantly decreased invasiveness when compared with GSCs
      treated with an miR-125b inhibitor or temozolomide alone. Further research into
      the underlying mechanism demonstrated that the miR-125b inhibitor enhanced the
      invasion-prevention activity of temozolomide in GSCs through targeting PIAS3
      (protein inhibitor of activated STAT [signal transducer and activator of
      transcription]), which contributed to reduced STAT3 transcriptional activity and
      subsequent decreased expression of matrix metalloproteinase (MMP)-2 and -9.
      CONCLUSIONS: miR-125b could play a role in the development of temozolomide
      resistance in GSCs. Inhibition of miR-125b expression may enhance sensitivity of
      GSCs to temozolomide by targeting PIAS3 on cell invasion.

PMID- 23857510
TI  - Synthesis of (2-alkylthiothiazolin-5-yl)methyl dodecanoates via tandem radical
      reaction.
AB  - A series of (2-alkylthiothiazolin-5-yl)methyl dodecanoates was synthesized from
      various alkyl N-allylcarbamodithioates and dilauroyl peroxide via a tandem
      radical hydrogen-abstraction-cyclization-substitution/combination reaction with a
      5-exo-trig radical cyclization as a key step. The current route is the first,
      convenient, and efficient synthesis of (2-alkylthiothiazolin-5-yl)methanol
      derivatives. 

PMID- 23857509
TI  - 2-epi-5-epi-Valiolone synthase activity is essential for maintaining
      phycobilisome composition in the cyanobacterium Anabaena variabilis ATCC 29413
      when grown in the presence of a carbon source.
AB  - The cyclase 2-epi-5-epi-valiolone synthase (EVS) is reported to be a key enzyme
      for biosynthesis of the mycosporine-like amino acid shinorine in the
      cyanobacterium Anabaena variabilis ATCC 29413. Subsequently, we demonstrated that
      an in-frame complete deletion of the EVS gene had little effect on in vivo
      production of shinorine. Complete segregation of the EVS gene deletion mutant
      proved difficult and was achieved only when the mutant was grown in the dark and
      in a medium supplemented with fructose. The segregated mutant showed a striking
      colour change from native blue-green to pale yellow-green, corresponding to
      substantial loss of the photosynthetic pigment phycocyanin, as evinced by
      combinations of absorbance and emission spectra. Transcriptional analysis of the
      mutant grown in the presence of fructose under dark or light conditions revealed
      downregulation of the cpcA gene that encodes the alpha subunit of phycocyanin,
      whereas the gene encoding nblA, a protease chaperone essential for phycobilisome
      degradation, was not expressed. We propose that the substrate of EVS
      (sedoheptulose 7-phosphate) or possibly lack of its EVS-downstream products,
      represses transcription of cpcA to exert a hitherto unknown control over
      photosynthesis in this cyanobacterium. The significance of this finding is
      enhanced by phylogenetic analyses revealing horizontal gene transfer of the EVS
      gene of cyanobacteria to fungi and dinoflagellates. It is also conceivable that
      the EVS gene has been transferred from dinoflagellates, as evident in the host
      genome of symbiotic corals. A role of EVS in regulating sedoheptulose 7-phosphate
      concentrations in the photophysiology of coral symbiosis is yet to be determined.

PMID- 23857511
TI  - Plasma and urine metabolic fingerprinting of type 1 diabetic children.
AB  - Type 1 diabetes mellitus is one of the most common chronic disorders of
      childhood. The metabolic control is lost due to the lack of insulin, which is the
      main treatment for the disease. Nevertheless, long-term complications appear even
      under good glycemic control. Metabolomics, an emerging strategy, can help in
      diagnosis, prognosis, and monitoring of metabolic disorders. The objective of the
      present study was to investigate the alterations in plasma (by LC-MS) and urine
      (CE-MS) of type 1 diabetic children that were under insulin treatment and good
      glycemic control. Even without remarkable biochemical differences between the two
      groups (diabetic and control) except for glucose level and glycosilated
      hemoglobin, metabolomic tools were able to capture subtle metabolic differences.
      The main changes in plasma were associated to lipidic metabolism (nonesterified
      fatty acids, lysophospholipids, and other derivatives of fatty acids), and some
      markers of the differential activity of the gut microflora were also found (bile
      acids, p-cresol sulfate). In urine, changes associated to protein and amino acid
      metabolism were found (amino acids, their metabolites and derivatives), and among
      them one advanced glycation end product (carboxyethylarginine) and one early
      glycation end product (fructosamine) were excreted in higher proportion in the
      diabetic group. 

PMID- 23857512
TI  - Platelet count and survival of patients with compensated cirrhosis and small
      hepatocellular carcinoma treated with surgery.

PMID- 23857513
TI  - 18F-flumazenil: a gamma-aminobutyric acid A-specific PET radiotracer for the
      localization of drug-resistant temporal lobe epilepsy.
AB  - Studies report that (11)C-flumazenil (FMZ) PET more specifically localizes the
      epileptogenic zone in patients with medically refractory focal epilepsy than
      (18)F-FDG PET. However, practical aspects of (11)C use limit clinical
      application. We report a phase I/IIa study assessing the clinical use of (18)F
      FMZ PET for the localization of the epileptogenic zone in patients with drug
      resistant temporal lobe epilepsy (TLE). Receptor binding was quantified using
      kinetic modeling that did not require arterial sampling. METHODS: Dynamic (18)F
      FMZ PET and static interictal (18)F-FDG PET scans were compared in healthy
      controls (n = 17 for (18)F-FMZ and n = 20 for (18)F-FDG) and TLE patients with
      mesial temporal sclerosis on MR imaging (MTS, n = 12) and with normal MR imaging
      (NL TLE, n = 19). Masked visual assessment of images was undertaken. Parametric
      images of (18)F-FMZ binding potential (BPND) were generated using the simplified
      reference tissue model. Region-of-interest analysis on coregistered MR images and
      statistical parametric mapping were used to quantify (18)F-FMZ BPND and (18)F-FDG
      uptake in the temporal lobe. RESULTS: The visual assessment of static
      standardized uptake value images showed (18)F-FMZ PET to have high specificity
      (16/17 [94%]) and moderate sensitivity (21/31 [68%]) for the localization of the
      epileptogenic zone, with a more restricted abnormality than (18)F-FDG PET.
      However, the (18)F-FMZ standardized uptake value images were falsely localizing
      in 3 of 31 patients (10%). Region-of-interest analysis demonstrated reductions in
      ipsilateral hippocampal (18)F-FMZ BPND in patients with either MTS or NL TLE,
      compared with controls subjects. Ipsilateral hippocampal (18)F-FMZ BPND was
      independent of both hippocampal volume and (18)F-FDG uptake, whereas ipsilateral
      hippocampal volume was correlated with (18)F-FDG uptake (r(2) = 0.69, P <
      0.0001). Statistical parametric mapping analysis demonstrated decreased uptake in
      14 of 31 (45%) cases with (18)F-FMZ PET and 18 of 29 (62%) with (18)F-FDG PET.
      Cluster size was significantly smaller on (18)F-FMZ than (18)F-FDG images (37 vs.
      160 voxels, P < 0.01). CONCLUSION: (18)F-FMZ PET has potential as a clinical tool
      for the localization of the epileptogenic zone in the presurgical evaluation of
      drug-resistant TLE, providing information complementary to (18)F-FDG PET, with a
      more restricted region of abnormality.

PMID- 23857514
TI  - Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau
      pathology in Alzheimer disease.
AB  - Neurofibrillary tangles in Alzheimer disease (AD) brains are composed of the
      microtubule-associated protein tau. Noninvasive monitoring of tau protein
      aggregates in the living brain will provide useful information regarding tau
      pathophysiology in AD. However, no PET probes are currently available for
      selective detection of tau pathology in AD. We have previously reported (18)F
      labeled THK-523 ((18)F-6-(2-fluoroethoxy)-2-(4-aminophenyl)quinoline) as a tau
      imaging radiotracer candidate for PET. After compound optimization, we developed
      novel (18)F-labeled arylquinoline derivatives, (18)F-THK-5105 and (18)F-THK-5117,
      for use as tau imaging PET tracers. METHODS: (18)F-labeled compounds were
      prepared from the corresponding tosylated precursors. The binding affinity of
      compounds to synthetic tau aggregates and tau-rich AD brain homogenates was
      determined by saturation and competition binding assays. The binding selectivity
      of compounds to tau pathology was evaluated by autoradiography of AD brain
      sections. The pharmacokinetics of compounds were assessed in biodistribution
      studies in normal mice. A 14-d toxicity study with intravenous administration of
      compounds was performed using rats and mice. RESULTS: In vitro binding assays
      demonstrated higher binding affinity of THK-5105 and THK-5117 than THK-523 to tau
      protein aggregates and tau-rich AD brain homogenates. Autoradiographic analyses
      of AD brain sections showed that these radiotracers preferentially bound to
      neurofibrillary tangles and neuropil threads, which colocalized with Gallyas
      positive and immunoreactive tau protein deposits. The distribution of this
      radiotracer binding in AD brain sections was completely different from that of
      (11)C-Pittsburgh compound B, showing preferential binding to amyloid plaques.
      Furthermore, these derivatives demonstrated abundant initial brain uptake and
      faster clearance in normal mice than (18)F-THK-523 and other reported (18)F
      labeled radiotracers. THK-5105 and THK-5117 showed no toxic effects related to
      the administration of these compounds in mice and rats and no significant binding
      for various neuroreceptors, ion channels, and transporters at 1-MUM
      concentrations. CONCLUSION: (18)F-labeled THK-5105 and THK-5117 are promising
      candidates as PET tau imaging radiotracers.

PMID- 23857515
TI  - Anticancer effects of marine carotenoids, fucoxanthin and its deacetylated
      product, fucoxanthinol, on osteosarcoma.
AB  - Survival of osteosarcoma patients hinges on prevention or treatment of recurrent
      and metastatic lesions. Therefore, novel chemotherapeutics for more effective
      treatment and prevention of this disease are required. Carotenoids are natural
      pigments and exhibit various biological functions. We evaluated the anti
      osteosarcoma properties of several carotenoids. Among carotenoids, fucoxanthin
      and its metabolite fucoxanthinol, inhibited the cell viability of osteosarcoma
      cell lines. Fucoxanthinol induced G1 cell cycle arrest by reducing the expression
      of cyclin-dependent kinase 4, cyclin-dependent kinase 6 and cyclin E and
      apoptosis by reducing the expression of survivin, XIAP, Bcl-2 and Bcl-xL.
      Apoptosis was associated with activation of caspases-3, -8 and -9. In addition,
      fucoxanthinol inhibited the phosphorylation of phosphoinositide-dependent kinase
      1 and Akt and the downstream glycogen synthase kinase 3beta, resulting in
      downregulation of beta-catenin. Fucoxanthinol inhibited the cell migration and
      invasion of osteosarcoma cells. It also reduced matrix metalloproteinase-1
      expression and the activator protein-1 signal. Treatment of mice inoculated with
      osteosarcoma cells with fucoxanthin inhibited the development of osteosarcoma in
      mice. Fucoxanthin and fucoxanthinol inhibit cell growth, migration and invasion
      and induce apoptosis of osteosarcoma cells at least in part by inhibiting Akt and
      activator protein-1 pathways. Our findings provide a rationale for clinical
      evaluation of these novel agents in osteosarcoma.

PMID- 23857516
TI  - Gender identities and gender dysphoria in the Netherlands.
AB  - Several studies estimate the prevalence of gender dysphoria among adults by
      examining the number of individuals turning to health services. Since individuals
      might be hesitant to seek medical care related to gender dysphoria, these studies
      could underestimate the prevalence. The studies also lack information regarding
      the variance among different aspects of gender dysphoric conditions. Therefore,
      the current study estimated the prevalence by examining self-reported gender
      identity and dysphoria in a Dutch population sample (N = 8,064, aged 15-70 years
      old). Three measures assessed aspects of gender dysphoria: gender identity,
      dislike of the natal female/male body, and wish to obtain hormones/sex
      reassignment surgery. Results showed that 4.6 % of the natal men and 3.2 % of the
      natal women reported an ambivalent gender identity (equal identification with
      other sex as with sex assigned at birth) and 1.1 % of the natal men and 0.8 % of
      the natal women reported an incongruent gender identity (stronger identification
      with other sex as with sex assigned at birth). Lower percentages reported a
      dislike of their natal body and/or a wish for hormones/surgery. Combining these
      figures estimated the percentage of men reporting an ambivalent or incongruent
      gender identity combined with a dislike of their male body and a wish to obtain
      hormones/surgery at 0.6 %. For women, this was 0.2 %. These novel findings show
      that studies based on the number of individuals seeking medical care might
      underestimate the prevalence of gender dysphoria. Furthermore, the findings argue
      against a dichotomous approach to gender dysphoria.

PMID- 23857518
TI  - Discordant transsexualism in male monozygotic twins: neuroanatomical and
      psychological differences.
AB  - One monozygotic male twin pair discordant for transsexualism is described. Both
      twins were interviewed and tested with the Wechsler Adult Intelligence Scale
      battery for cognitive functions and they underwent magnetic resonance imaging to
      measure the volumes of specific cerebral structures. Interviews with the twins
      and their mother indicated no unusual medical or life history events that could
      have had a causal role in the emergence of the disorder. Both cognitive function
      testing and neuroimaging detected differences between the twins that could be
      related to unexplained epigenetic effects and exogenous hormone usage.

PMID- 23857517
TI  - Sexual victimization, alcohol intoxication, sexual-emotional responding, and
      sexual risk in heavy episodic drinking women.
AB  - This study used an experimental paradigm to investigate the roles of sexual
      victimization history and alcohol intoxication in young women's sexual-emotional
      responding and sexual risk taking. A nonclinical community sample of 436 young
      women, with both an instance of heavy episodic drinking and some HIV/STI risk
      exposure in the past year, completed childhood sexual abuse (CSA) and
      adolescent/adult sexual assault (ASA) measures. A majority of them reported CSA
      and/or ASA, including rape and attempted rape. After random assignment to a high
      alcohol dose (.10 %) or control condition, participants read and projected
      themselves into an eroticized scenario of a sexual encounter involving a new
      partner. As the story protagonist, each participant rated her positive mood and
      her sexual arousal, sensation, and desire, and then indicated her likelihood of
      engaging in unprotected sex. Structural equation modeling analyses revealed that
      ASA and alcohol were directly associated with heightened risk taking, and
      alcohol's effects were partially mediated by positive mood and sexual desire. ASA
      was associated with attenuated sexual-emotional responding and resulted in
      diminished risk taking via this suppression. These are the first findings
      indicating that, compared to non-victimized counterparts, sexually victimized
      women respond differently in alcohol-involved sexual encounters in terms of
      sexual-emotional responding and risk-taking intentions. Implications include
      assessing victimization history and drinking among women seeking treatment for
      either concern, particularly women at risk for HIV, and alerting them to ways
      their histories and behavior may combine to exacerbate their sexual risks.

PMID- 23857519
TI  - Human female orgasm as evolved signal: a test of two hypotheses.
AB  - We present the results of a study designed to empirically test predictions
      derived from two hypotheses regarding human female orgasm behavior as an evolved
      communicative trait or signal. One hypothesis tested was the female fidelity
      hypothesis, which posits that human female orgasm signals a woman's sexual
      satisfaction and therefore her likelihood of future fidelity to a partner. The
      other was sire choice hypothesis, which posits that women's orgasm behavior
      signals increased chances of fertilization. To test the two hypotheses of human
      female orgasm, we administered a questionnaire to 138 females and 121 males who
      reported that they were currently in a romantic relationship. Key predictions of
      the female fidelity hypothesis were not supported. In particular, orgasm was not
      associated with female sexual fidelity nor was orgasm associated with male
      perceptions of partner sexual fidelity. However, faked orgasm was associated with
      female sexual infidelity and lower male relationship satisfaction. Overall,
      results were in greater support of the sire choice signaling hypothesis than the
      female fidelity hypothesis. Results also suggest that male satisfaction with,
      investment in, and sexual fidelity to a mate are benefits that favored the
      selection of orgasmic signaling in ancestral females.

PMID- 23857520
TI  - The social and policy context of curing syphilis: Commentary on Francis (2013).

PMID- 23857521
TI  - Locally-Constrained Region-Based Methods for DW-MRI Segmentation.
AB  - In this paper, we describe a method for segmenting fiber bundles from diffusion
      weighted magnetic resonance images using a locally-constrained region based
      approach. From a pre-computed optimal path, the algorithm propagates outward
      capturing only those voxels which are locally connected to the fiber bundle.
      Rather than attempting to find large numbers of open curves or single fibers,
      which individually have questionable meaning, this method segments the full fiber
      bundle region. The strengths of this approach include its ease-of-use,
      computational speed, and applicability to a wide range of fiber bundles. In this
      work, we show results for segmenting the cingulum bundle. Finally, we explain how
      this approach and extensions thereto overcome a major problem that typical region
      based flows experience when attempting to segment neural fiber bundles.

PMID- 23857522
TI  - Measuring competence makes revalidation easier.

PMID- 23857523
TI  - Postpartum misoprostol for preventing maternal mortality and morbidity.
AB  - BACKGROUND: The primary objective of postpartum haemorrhage (PPH) prevention and
      treatment is to reduce maternal deaths. Misoprostol has the major public health
      advantage over injectable medication that it can more easily be distributed at
      community level. Because misoprostol might have adverse effects unrelated to
      blood loss which might impact on mortality or severe morbidity, it is important
      to continue surveillance of all relevant evidence from randomised trials. This is
      particularly important as misoprostol is being introduced on a large scale for
      PPH prevention in low-income countries, and is commonly used for PPH treatment in
      well-resourced settings as well. OBJECTIVES: To review maternal deaths and severe
      morbidity in all randomised trials of misoprostol for prevention or treatment of
      PPH. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's
      Trials Register (11 January 2013). SELECTION CRITERIA: We included randomised
      trials including pregnant women who received misoprostol in the postpartum
      period, versus placebo/no treatment or other uterotonics for prevention or
      treatment of PPH, and reporting on maternal death, severe morbidity or pyrexia.We
      planned to include cluster- and quasi-randomised trials in the analysis, as a
      very large number of women will be needed to obtain robust estimates of maternal
      mortality but we did not identify any for this version of the review. In future
      updates of this review we will include trials reported only as abstracts if
      sufficient information is available from the abstract or from the authors. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
      inclusion and extracted data. MAIN RESULTS: We included 78 studies (59,216 women)
      and excluded 34 studies.There was no statistically significant difference in
      maternal mortality for misoprostol compared with control groups overall (31
      studies; 11/19,715 versus 4/20,076 deaths; risk ratio (RR) 2.08, 95% confidence
      interval (CI) 0.82 to 5.28); or for the trials of misoprostol versus placebo: 10
      studies, 6/4626 versus 1/4707 ; RR 2.70; 95% CI 0.72 to 10.11; or for misoprostol
      versus other uterotonics: 21 studies, 5/15,089 versus 3/15,369 (19/100,000); RR
      1.54; 95% CI 0.40 to 5.92. All 11 deaths in the misoprostol arms occurred in
      studies of misoprostol >= 600 ug.There was a statistically significant difference
      in the composite outcome 'maternal death or severe morbidity' for the comparison
      of misoprostol versus placebo (12 studies; average RR 1.70, 95% CI 1.02 to 2.81;
      Tau2 = 0.00, I2 = 0%) but not for the comparison of misoprostol versus other
      uterotonics (17 studies; average RR 1.50, 95% CI 0.50 to 4.52; Tau2 = 1.81, I2 =
      69%). When we excluded hyperpyrexia from the composite outcome in exploratory
      analyses, there was no significant difference in either of these
      comparisons.Pyrexia > 38 degrees C was increased with misoprostol compared with
      controls (56 studies, 2776/25,647 (10.8%) versus 614/26,800 (2.3%); average RR
      3.97, 95% CI 3.13 to 5.04; Tau2 = 0.47, I2 = 80%). The effect was greater for
      trials using misoprostol 600 ug or more (27 studies; 2197/17,864 (12.3%) versus
      422/18,161 (2.3%); average RR 4.64; 95% CI 3.33 to 6.46; Tau2 = 0.51, I2 = 86%)
      than for those using misoprostol 400 ug or less (31 studies; 525/6751 (7.8%)
      versus 185/7668 (2.4%); average RR 3.07; 95% CI 2.25 to 4.18; Tau2 = 0.29, I2 =
      58%). AUTHORS' CONCLUSIONS: Misoprostol does not appear to increase or reduce
      severe morbidity (excluding hyperpyrexia) when used to prevent or treat PPH.
      Misoprostol did not increase or decrease maternal mortality. However, misoprostol
      is associated with an increased risk of pyrexia, particularly in dosages of 600
      ug or more. Given that misoprostol is used prophylactically in very large numbers
      of healthy women, the greatest emphasis should be placed on limiting adverse
      effects. In this context, the findings of this review support the use of the
      lowest effective dose. As for any new medication being used on a large scale,
      continued vigilance for adverse effects is essential and there is a need for
      large randomised trials to further elucidate both the relative effectiveness and
      the risks of various dosages of misoprostol.

PMID- 23857524
TI  - Chemistry and formulations for siRNA therapeutics.
AB  - Small interfering ribonucleic acids (siRNAs) form potentially the most important
      class of next generation therapeutics. However, achieving their efficient
      delivery in the correct dose, time and location in the body remains a significant
      challenge. Rapid developments in the chemistries of siRNA formulations are
      enabling new strategies to overcome the core obstacles to delivery which include
      poor ribonuclease (RNase) resistance, short biological half-life, lack of tissue
      targeting, inefficient cellular uptake and undesirable toxicity. In this review
      we describe these principal challenges and evaluate recent approaches proposed to
      overcome the chemical, biochemical and physiological barriers. The role of the
      specific chemical structure of siRNA is considered and an overview of selected
      literature-reported siRNA formulations is provided. These include chemically
      modified siRNAs and analogues, aptamer-siRNA chimeras, self-assembled
      nanoparticles, lipid and polymer complexes, bioconjugates and fusion protein
      complexes. We conclude the review with an outlook for the clinical use of this
      highly promising, but pharmaceutically challenging biotherapeutic. 

PMID- 23857525
TI  - BEVA survey suggests oversupply of equine vets.

PMID- 23857526
TI  - Job prospects for new graduates 'not as gloomy as predicted'.

PMID- 23857527
TI  - Guidance on using flukicides in dairy cattle.

PMID- 23857528
TI  - Government plans to move away from 'one-size-fits-all' approach to bovine TB.

PMID- 23857531
TI  - A brief history of Veterinary Record.

PMID- 23857532
TI  - Veterinary Record Open: extending the open access options.

PMID- 23857533
TI  - Introducing the editor of Veterinary Record Open.

PMID- 23857534
TI  - A review of diagnostic imaging of snakes and lizards.
AB  - Snakes and lizards are considered 'stoic' animals and often show only non
      specific signs of illness. Consequently, diagnostic imaging--along with clinical
      examination and laboratory tests--is gaining importance in making a final
      diagnosis and establishing a correct therapy. The large number of captive snake
      and lizard species commonly kept as pets, together with the high inter- and
      intraspecific morphological variability that is innate in these animals, make the
      analysis of diagnostic images challenging for the veterinary practitioner.
      Moreover, a thorough knowledge of the anatomy, physiology and pathology of the
      species that are the object of clinical investigation is mandatory for the
      correct interpretation of diagnostic images. Despite the large amount of clinical
      and scientific work carried out in the past two decades, the radiographic
      features of snakes and lizards have not undergone systematic description, and
      therefore veterinarians often have to rely mostly on anatomical studies rather
      than radiological literature. The aim of this paper is to review the most
      commonly used diagnostic imaging modalities, as well as to provide an overview of
      the available international original studies and scientific reviews describing
      the normal and pathological imaging features in snakes and lizards.

PMID- 23857535
TI  - Pinioning non-agricultural birds.

PMID- 23857536
TI  - Fellowship by thesis.

PMID- 23857537
TI  - Veterinary education in Northern Ireland.

PMID- 23857538
TI  - Badger culling pilots.

PMID- 23857539
TI  - Misoprostol vaginal insert and time to vaginal delivery: a randomized controlled
      trial.
AB  - OBJECTIVE: To compare the efficacy and safety of a 200-microgram misoprostol
      vaginal insert with a 10-mg dinoprostone vaginal insert for reducing the time to
      vaginal delivery. METHODS: In a phase III, double-blind, multicenter study, women
      being induced with a modified Bishop score of 4 or less were randomly assigned to
      receive either a 200-microgram misoprostol vaginal insert or a 10-mg dinoprostone
      vaginal insert. Coprimary end points were time to vaginal delivery and rate of
      cesarean delivery. Secondary end points included time to any delivery mode, time
      to onset of active labor, and oxytocin use. RESULTS: A total of 1,358 women were
      randomized to receive the 200-microgram misoprostol vaginal insert (n=678) or
      dinoprostone vaginal insert (n=680). Women receiving the misoprostol vaginal
      insert had a significantly shorter median time to vaginal delivery compared with
      patients receiving the dinoprostone vaginal insert (21.5 hours compared with 32.8
      hours, P<.001). Cesarean delivery occurred in 26.0% and 27.1% of women receiving
      the misoprostol vaginal insert and dinoprostone vaginal insert, respectively. A
      significant reduction in time to any delivery (18.3 hours compared with 27.3
      hours), time to onset of active labor (12.1 hours compared with 18.6 hours), and
      proportion of women requiring predelivery oxytocin (48.1% compared with 74.1%)
      was observed with the misoprostol vaginal insert compared with dinoprostone
      vaginal insert (P<.001 for each). Uterine tachysystole requiring intervention
      occurred in 13.3% and 4.0% of participants receiving the misoprostol vaginal
      insert and dinoprostone vaginal insert, respectively (P<.001). CONCLUSION: Use of
      a 200-microgram misoprostol vaginal inset significantly reduced times to vaginal
      delivery and active labor with reduced need for oxytocin compared with the
      dinoprostone vaginal insert. Cesarean delivery rates were similar with both
      treatments. Tachysystole was more common in women receiving the 200-microgram
      misoprostol vaginal insert. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT01127581. LEVEL OF EVIDENCE: I.

PMID- 23857540
TI  - Conceptual confluence: the kynurenine pathway as a common target for ketamine and
      the convergence of the inflammation and glutamate hypotheses of depression.

PMID- 23857541
TI  - Magneto-optical nanomaterials: a SPIO-phthalocyanine scaffold built step-by-step
      towards bimodal imaging.
AB  - A SPIO-phthalocyanine nanohybrid is developed as a bimodal contrast agent for
      Optical and Magnetic Resonance Imaging. The organic coating was covalently
      attached onto SPIO in a step-by-step approach. Each coated-SPIO was thoroughly
      characterized. The hydrodynamic size of the SPIO-Pc is ca. 60 nm with a coverage
      of ca. 690 Pc/SPIO. 

PMID- 23857542
TI  - S-nitrosylation regulates mitochondrial quality control via activation of parkin.
AB  - Parkin, a ubiquitin E3 ligase of the ring between ring fingers family, has been
      implicated in mitochondrial quality control. A series of recent reports have
      suggested that the recruitment of parkin is regulated by phosphorylation.
      However, the molecular mechanism that activates parkin to induce mitochondrial
      degradation is not well understood. Here, and in contrast to previous reports
      that S-nitrosylation of parkin is exclusively inhibitory, we identify a
      previously unrecognized site of S-nitrosylation in parkin (Cys323) that induces
      mitochondrial degradation. We demonstrate that endogenous S-nitrosylation of
      parkin is in fact responsible for activation of its E3 ligase activity to induce
      aggregation and degradation. We further demonstrate that mitochondrial uncoupling
      agents result in denitrosylation of parkin, and that prevention of
      denitrosylation restores mitochondrial degradation. Our data indicates that NO
      both positive effects on mitochondrial quality control, and suggest that targeted
      S-nitrosylation could provide a novel therapeutic strategy against Parkinson's
      disease. 

PMID- 23857544
TI  - Novel focal adhesion protein kindlin-2 promotes the invasion of gastric cancer
      cells through phosphorylation of integrin beta1 and beta3.
AB  - BACKGROUND: We have found that the expression of the novel focal adhesion protein
      kindlin-2 had a significant positive correlation with poor survival in gastric
      cancer. However, the mechanism by which kindlin-2 acts in gastric cancer warrants
      further evaluation. METHODS: Kindlin-2 mRNA expression in gastric cancer cell
      lines was measured by realtime RT-PCR under normal and hypoxic conditions. Cell
      proliferation, apoptosis, cell cycle, tumor adhesion, cell invasion ability, and
      phosphorylation of integrin beta1 and beta3 proteins were measured to assess the
      influence of kindlin-2 on the malignant behavior of gastric cancer cells.
      RESULTS: Kindlin-2 mRNA expression was highest in the distant metastasis gastric
      cancer cell line Hs-746T. Cell proliferation, adhesion with endothelium and
      collagen IV, invasion rate, and angiogenesis genes expression, as well as
      phosphorylation of integrin beta1 and beta3 in Hs-746T, were decreased
      significantly after kindlin-2 downregulation, but there was no change in
      apoptosis and cell cycle. CONCLUSIONS: Kindlin-2 might promote the invasion of
      gastric cancer cells through enhancing proliferation and adhesion by the
      phosphorylation of integrin beta1 and beta3.

PMID- 23857545
TI  - Solvent effect on the nonlinear absorption of 5,10-A(2)B(2) meso substituted
      porphyrins.
AB  - The effect of the solvent on the nonlinear absorptive properties of two series of
      5,10-A2B2 porphyrins was investigated with an open Z-scan technique in the ns
      time regime. The recorded responses, which varied between compounds and solvents,
      were fitted to a four-level model where the one-photon excited state absorption
      is followed by a two-photon process arising from the higher excited states. For
      most of the compounds the positive nonlinear absorption in toluene was stronger
      than that in DMF and chloroform. This was attributed to enhanced two-photon
      absorption in toluene. For DMF and chloroform the solvent effects were most
      likely to be compound specific. It was demonstrated that the high saturation
      intensity of two-photon absorption shifts the RSA/SA turnover into a higher
      fluence range, which is desirable for optical limiting applications. This
      saturation intensity of two-photon absorption varied between compounds and
      solvents. Additionally, nonlinear scattering contributed strongly to the open Z
      scan responses for many compounds in chlorobenzene and chloroform-chlorobenzene
      solutions. This was associated with the photodegradation of chlorobenzene. 

PMID- 23857546
TI  - Male urogenital infections: impact of infection and inflammation on ejaculate
      parameters.
AB  - BACKGROUND: Urogenital infections and inflammation may contribute significantly
      to ejaculate parameters essential for male infertility. METHODS: For this review,
      data were acquired by a systematic search of the medical literature of the last 5
      years. RESULTS: We address the andrological relevance of male urogenital
      infections and inflammation on ejaculate parameters. The different classification
      systems of the WHO and NIH are illustrated. In most cases, a separation of the
      different areas of the urogenital tract, for example, of the prostate, epididymis
      and testicles, is not possible. The significance of bacteriospermia with common
      bacteria is discussed. Furthermore, HIV, ascending chlamydial, mycoplasmal and
      gonococcal infections are relevant. Especially, the relevance of sexually
      transmitted microorganisms seems to be underestimated. Leukocytospermia is not
      well defined in its biological significance. Seminal plasma elastase and the
      cytokine expression reveal better insights into the inflammatory response of the
      seminal pathways. Sperm antibodies and reactive oxygen species are not usable as
      indicators for infection and inflammation. Different aspects for an impairment of
      ejaculate quality have been demonstrated although a direct ascension of
      microorganisms to the prostate has not been confirmed. Probably, lesions of the
      epididymis may sustain an ongoing disturbance of sperm parameters. A potential
      negative influence of urogenital infections and inflammation on sperm function is
      under discussion. However, the severity of impairment differs according to the
      underlying infections and the involved compartments. CONCLUSIONS: Signs of
      infections and inflammation in the ejaculate of infertile men are common, and the
      relevance is often doubtful in spite of microbiological, spermatological and
      immunological facilities.

PMID- 23857548
TI  - Giant peripheral ossifying fibroma: a case report and clinicopathologic review of
      10 cases from the literature.
AB  - Peripheral ossifying fibroma (POF) is most often a self-limiting, sessile or
      pedunculated, gingival nodule that is believed to be a reactive rather than
      neoplastic pathologic process. The lesion is typically <2cm, however it has been
      recognized that some examples may grow quite large and may displace teeth. The
      mass-like clinical presentation and radiographic appearance of soft tissue
      calcification may lead to misclassification; however the histologic appearance is
      diagnostic. Giant POFs (GPOF) have been referred to in the literature by several
      other names (large, atypical, huge, gigantiform). The distinguishing
      characteristics of GPOFs and the factors that contribute to their growth have
      primarily been explored through case reports. We present a new case of POF that
      was giant and review 10 previously reported giant lesions, with focus on the
      clinical presentation, radiographic features, and outcome to explore the
      possibility that this represents a distinct clinical subset of lesion, with a
      unique set of features that warrant recognition for accurate diagnosis. 

PMID- 23857551
TI  - Pathological implications of Th1/Th2 cytokine genetic variants in Behcet's
      disease: Data from a pilot study in a Sicilian population.
AB  - Cytokines act as pleiotropic polypeptides able to regulate inflammatory/immune
      responses and to provide important signals in physiological and pathological
      processes. Several cytokines (Th1, Th2, and Th17) seem to be involved in the
      pathophysiology of Behcet's disease, a chronic immune-mediated disease
      characterized by oral and genital lesions and ocular inflammation. Its individual
      susceptibility seems to be modulated by genetic variants in genes codifying these
      cytokines. Th1 and Th17 seem to be involved in the disease's active phases, and
      Th2 seems to affect the development or severity of the disease; however,
      contrasting data are reported. In this study, some genetic variants of the
      Th1/Th2 cytokine genes were investigated in Sicilian patients and age- and gender
      matched controls. Three very significant associations with Behcet's disease were
      detected, and combined genotypes associated with increased disease risk were
      identified. Results obtained point to the key role of Th1/Th2 cytokine genetic
      variants in disease susceptibility.

PMID- 23857550
TI  - Protective effect of the herbal medicine Gan-fu-kang against carbon tetrachloride
      induced liver fibrosis in rats.
AB  - The aim of the present study was to investigate the effect of a herbal medicine
      formula, Gan-fu-kang (GFK), on the treatment of liver fibrosis in rats and the
      mechanisms via which it exerts its effect. Liver fibrosis was induced in rats by
      subcutaneous injection of carbon tetrachloride (CCl4) at 0.5 mg/kg body weight,
      twice a week for 8 weeks. The rats were randomly selected to receive saline or
      GFK at 31.25, 312.5 or 3,125 mg/kg body weight/day between weeks 9 and 20. An
      additional group of rats without CCl4 injection was used as the baseline. In the
      liver fibrosis model rats, an increase in plasma liver enzymes, fibrotic markers
      in serum and liver fibrosis, production of alpha-smooth muscle actin, matrix
      metalloproteinase-2 and tissue inhibitor of metalloproteinase-1, synthesis of
      collagen and activation of the Wnt/beta-catenin signaling pathway were observed.
      GFK administration was found to significantly reduce these changes. Results of
      this study demonstrate that GFK has a protective and therapeutic effect on liver
      fibrosis induced by CCl4, which may be associated with its inhibitory activity on
      HSC proliferation and collagen synthesis, effectively downregulating Wnt/beta
      catenin signaling.

PMID- 23857549
TI  - Management of neurogenic orthostatic hypotension in patients with autonomic
      failure.
AB  - The maintenance of blood pressure in the upright position requires intact
      autonomic cardiovascular reflexes. Diseases that affect the sympathetic
      innervation of the cardiovascular system result in a sustained fall in blood
      pressure upon standing (i.e., neurogenic orthostatic hypotension) that can impair
      the blood supply to the brain and other organs and cause considerable morbidity
      and mortality. Here we review treatment options for neurogenic orthostatic
      hypotension and include an algorithm for its management that emphasizes the
      importance of non-pharmacologic measures and provides guidance on pharmacologic
      treatment options. 

PMID- 23857552
TI  - Proton concentrations can be a major contributor to the modification of
      osteoclast and osteoblast differentiation, working independently of extracellular
      bicarbonate ions.
AB  - We established a system to separately analyze the role of protons and bicarbonate
      ions in vitro in which the pH of the medium was controlled by HEPES at various
      concentrations of sodium bicarbonate (NaHCO3) in the absence of carbon dioxide
      (CO2). Using this system, we demonstrated that acidosis promoted osteoclast
      formation independently of extracellular NaHCO3 in a short-term culture. Protons
      and bicarbonate ions acted on osteoclast differentiation with opposite effects,
      the former positively and the latter negatively. The HEPES-based system
      maintained pH in the absence of extracellular NaHCO3 without CO2. Therefore, we
      could demonstrate that osteoblast differentiation was promoted at higher pH in a
      long-term culture system without NaHCO3 in which ALP activity and nodule
      mineralization were enhanced. This finding indicates that protons negatively
      control osteoblast differentiation independently of extracellular bicarbonate
      ions. However, the difference in the concentration of NaHCO3 did not have any
      influence on nodule mineralization. The opposite effects of protons, the
      promotion of osteoclast formation and the inhibition of osteoblast
      differentiation, were suppressed in the presence of 5 mM N-acetyl cysteine, a
      reagent activating the scavenging of reactive oxygen species (ROS), implying that
      ROS act on both systems, the promotion of large osteoclast formation and the
      deterioration of osteoblast formation under acidosis. 

PMID- 23857553
TI  - Fast real-time NMR methods for characterizing short-lived molecular states.
AB  - The characterization of both the structure and the conformational dynamics of
      biological macromolecules, namely proteins and nucleic acids, is required for
      understanding the molecular mechanisms underlying physiological function and
      disease. Molecular dynamics involves the transient departure from the ground
      state structures to populate short-lived excited state conformations that can
      play important functional roles. Real-time multi-dimensional NMR spectroscopy
      represents a unique tool for investigating dynamic molecular processes occurring
      on time scales of seconds or longer, providing atomic-resolution information
      about short-lived states. In this minireview, we discuss recent progress made in
      the field of fast real-time multidimensional NMR. The potential of these new
      methods is illustrated for several biomolecular systems that have recently been
      studied by fast real-time multidimensional NMR. 

PMID- 23857554
TI  - Multiple imputation for handling systematically missing confounders in meta
      analysis of individual participant data.
AB  - A variable is 'systematically missing' if it is missing for all individuals
      within particular studies in an individual participant data meta-analysis. When a
      systematically missing variable is a potential confounder in observational
      epidemiology, standard methods either fail to adjust the exposure-disease
      association for the potential confounder or exclude studies where it is missing.
      We propose a new approach to adjust for systematically missing confounders based
      on multiple imputation by chained equations. Systematically missing data are
      imputed via multilevel regression models that allow for heterogeneity between
      studies. A simulation study compares various choices of imputation model. An
      illustration is given using data from eight studies estimating the association
      between carotid intima media thickness and subsequent risk of cardiovascular
      events. Results are compared with standard methods and also with an extension of
      a published method that exploits the relationship between fully adjusted and
      partially adjusted estimated effects through a multivariate random effects meta
      analysis model. We conclude that multiple imputation provides a practicable
      approach that can handle arbitrary patterns of systematic missingness. Bias is
      reduced by including sufficient between-study random effects in the imputation
      model.

PMID- 23857547
TI  - In-hospital and 1-year mortality in patients undergoing early surgery for
      prosthetic valve endocarditis.
AB  - IMPORTANCE: There are limited prospective, controlled data evaluating survival in
      patients receiving early surgery vs medical therapy for prosthetic valve
      endocarditis (PVE). OBJECTIVE: To determine the in-hospital and 1-year mortality
      in patients with PVE who undergo valve replacement during index hospitalization
      compared with patients who receive medical therapy alone, after controlling for
      survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS:
      Participants were enrolled between June 2000 and December 2006 in the
      International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a
      prospective, multinational, observational cohort of patients with infective
      endocarditis. Patients hospitalized with definite right- or left-sided PVE were
      included in the analysis. We evaluated the effect of treatment assignment on
      mortality, after adjusting for biases using a Cox proportional hazards model that
      included inverse probability of treatment weighting and surgery as a time
      dependent covariate. The cohort was stratified by probability (propensity) for
      surgery, and outcomes were compared between the treatment groups within each
      stratum. INTERVENTIONS: Valve replacement during index hospitalization (early
      surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES: In-hospital and 1-year
      mortality. RESULTS: Of the 1025 patients with PVE, 490 patients (47.8%) underwent
      early surgery and 535 individuals (52.2%) received medical therapy alone.
      Compared with medical therapy, early surgery was associated with lower in
      hospital mortality in the unadjusted analysis and after controlling for treatment
      selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38
      0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower
      mortality associated with surgery did not persist after adjustment for survivor
      bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality:
      HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital
      mortality with early surgery in the highest surgical propensity quintile (21.2%
      vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was
      observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P =
      .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE: Prosthetic
      valve endocarditis remains associated with a high 1-year mortality rate. After
      adjustment for differences in clinical characteristics and survival bias, early
      valve replacement was not associated with lower mortality compared with medical
      therapy in the overall cohort. Further studies are needed to define the effect
      and timing of surgery in patients with PVE who have indications for surgery.

PMID- 23857555
TI  - Zn- and Mg- containing tricalcium phosphates-based adjuvants for cancer
      immunotherapy.
AB  - Zn-, and Mg-containing tricalcium phosphates (TCPs) loaded with a hydrothermal
      extract of a human tubercle bacillus (HTB) were prepared by immersing Zn-TCP and
      Mg-TCP in HTB-containing supersaturated calcium phosphate solutions. The in vitro
      and in vivo immunogenic activities of the HTB-loaded Zn-, and Mg-TCPs (Zn-Ap-HTB
      and Mg-Ap-HTB, respectively) were evaluated as potential immunopotentiating
      adjuvants for cancer immunotherapy. The Zn-Ap-HTB and Mg-Ap-HTB adjuvants showed
      no obvious cytotoxicity and more effectively stimulated granulocyte-macrophage
      colony-stimulating factor (GM-CSF) secretion by macrophage-like cells than
      unprocessed HTB or HTB-loaded TCP (T-Ap-HTB) in vitro. Zn-Ap-HTB and Mg-Ap-HTB
      mixed with liquid-nitrogen-treated tumor tissue markedly inhibited the in vivo
      development of rechallenged Lewis lung carcinoma (LLC) cells compared with T-Ap
      HTB and the unprocessed HTB mixed liquid-nitrogen-treated tumor tissue. Zn-Ap-HTB
      and Mg-Ap-HTB contributed to eliciting potent systemic antitumor immunity in
      vivo. 

PMID- 23857556
TI  - Biosafety considerations of RNAi-mediated virus resistance in fruit-tree
      cultivars and in rootstock.
AB  - A major application of RNA interference (RNAi) is envisaged for the production of
      virus-resistant transgenic plants. For fruit trees, this remains the most, if not
      the only, viable option for the control of plant viral disease outbreaks in
      cultivated orchards, due to the difficulties associated with the use of
      traditional and conventional disease-control measures. The use of RNAi might
      provide an additional benefit for woody crops if silenced rootstock can
      efficiently transmit the silencing signal to non-transformed scions, as has
      already been demonstrated in herbaceous plants. This would provide a great
      opportunity to produce non-transgenic fruit from transgenic rootstock. In this
      review, we scrutinise some of the concerns that might arise with the use of RNAi
      for engineering virus-resistant plants, and we speculate that this virus
      resistance has fewer biosafety concerns. This is mainly because RNAi-eliciting
      constructs only express small RNA molecules rather than proteins, and because
      this technology can be applied using plant rootstock that can confer virus
      resistance to the scion, leaving the scion untransformed. We discuss the main
      biosafety concerns related to the release of new types of virus-resistant plants
      and the risk assessment approaches in the application of existing regulatory
      systems (in particular, those of the European Union, the USA, and Canada) for the
      evaluation and approval of RNAi-mediated virus-resistant plants, either as
      transgenic varieties or as plant virus resistance induced by transgenic
      rootstock.

PMID- 23857558
TI  - Capillary electrophoresis-mass spectrometry-based metabolome analysis of serum
      and saliva from neurodegenerative dementia patients.
AB  - Despite increasing global prevalence, the precise pathogenesis and terms for
      objective diagnosis of neurodegenerative dementias remain controversial, and
      comprehensive understanding of the disease remains lacking. Here, we conducted
      metabolomic analysis of serum and saliva obtained from patients with
      neurodegenerative dementias (n = 10), including Alzheimer's disease,
      frontotemporal lobe dementia, and Lewy body disease, as well as from age-matched
      healthy controls (n = 9). Using CE-TOF-MS, six metabolites in serum (beta
      alanine, creatinine, hydroxyproline, glutamine, iso-citrate, and cytidine) and
      two in saliva (arginine and tyrosine) were significantly different between
      dementias and controls. Using multivariate analysis, serum was confirmed as a
      more efficient biological fluid for diagnosis compared to saliva; additionally,
      45 metabolites in total were identified as candidate markers that could
      discriminate at least one pair of diagnostic groups from the healthy control
      group. These metabolites possibly provide an objective method for diagnosing
      dementia-type by multiphase screening. Moreover, diagnostic-type-dependent
      differences were observed in several tricarboxylic acid cycle compounds detected
      in serum, indicating that some pathways in glucose metabolism may be altered in
      dementia patients. This pilot study revealed novel alterations in metabolomic
      profiles between various neurodegenerative dementias, which would contribute to
      etiological investigations. 

PMID- 23857559
TI  - Controlling the interaction of light with polymer semiconductors.
AB  - In this study, a generally applicable strategy is described to manipulate the
      optical properties of a wide range of polymer semiconductors in the solid state.
      Blending these materials with a non-conjugated, polar polymer matrix is found to
      be the processing key to a drastic change and red-shift of the absorption
      characteristics. 

PMID- 23857557
TI  - Pig transgenesis by piggyBac transposition in combination with somatic cell
      nuclear transfer.
AB  - The production of animals by somatic cell nuclear transfer (SCNT) is inefficient,
      with approximately 2% of micromanipulated oocytes going to term and resulting in
      live births. However, it is the most commonly used method for the generation of
      cloned transgenic livestock as it facilitates the attainment of transgenic
      animals once the nuclear donor cells are stably transfected and more importantly
      as alternatives methods of transgenesis in farm animals have proven even less
      efficient. Here we describe piggyBac-mediated transposition of a transgene into
      porcine primary cells and use of these genetically modified cells as nuclear
      donors for the generation of transgenic pigs by SCNT. Gene transfer by piggyBac
      transposition serves to provide an alternative approach for the transfection of
      nuclear donor cells used in SCNT.

PMID- 23857560
TI  - A novel miniaturized radiofrequency potentiometer tag using ion-selective
      electrodes for wireless ion sensing.
AB  - Instrumental approaches to remotely and wirelessly monitoring chemical species
      are increasingly needed. Together with the electronic developments, efforts to
      optimize and validate the performance of these new devices are required. In this
      work, the analytical performance of a recently developed potentiometer
      radiofrequency tag connected to ion-selective electrodes is evaluated. This
      credit card sized and extremely low power consumption device yield results that
      are comparable to those obtained with more sophisticated, lab-based tools.
      Advantages such as portability and autonomy, together with unique features, such
      as the ability to be read through the walls in a closed vessel are demonstrated.
      Future perspectives opened by this new generation of devices, such as their use
      in wearable devices and in decentralized settings are discussed. 

PMID- 23857561
TI  - Hitching the gallbladder in laparoscopic-assisted cholecysto-cholangiography: a
      simple technique.
AB  - Neonatal cholestatic disorder in the late neonatal period requires often
      cholangiography to differentiate between biliary atresia and other causes of
      prolonged neonatal jaundice. A simplified method of a laparoscopic-assisted
      cholecysto-cholangiography is presented. Retrospective chart review was conducted
      of all patients who from May 2002 to April 2012 underwent a laparoscopic-assisted
      cholecysto-cholangiography with routine fixation of the fundus of the gallbladder
      to the lateral aspect of the abdominal wall. A total of 18 infants (8 boys) aged
      41-104 (median 64) days underwent laparoscopic-assisted cholecysto
      cholangiography for prolonged jaundice. The technique identified ten cases of a
      patent bile duct system and eight biliary atresias. (Thirty-two cases of
      suspected biliary atresia were confirmed by laparoscopy alone.) Two cases
      required suturing of a bile leak at the puncture site. Hitching the gallbladder
      to the lateral abdominal wall is a simple method allowing an optimal radiographic
      assessment of the extra- and intra-hepatic bile duct anatomy.

PMID- 23857562
TI  - Once versus twice daily low molecular weight heparin for the initial treatment of
      venous thromboembolism.
AB  - BACKGROUND: In the initial treatment of venous thromboembolism (VTE) low
      molecular weight heparin (LMWH) is administered once or twice daily. A once daily
      treatment regimen is more convenient for the patient and may optimise home
      treatment. However, it is not clear whether a once daily treatment regimen is as
      safe and effective as a twice daily treatment regimen. This is the second update
      of a review first published in 2003. OBJECTIVES: To compare the efficacy and
      safety of once daily versus twice daily administration of LMWH. SEARCH METHODS:
      For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co
      ordinator searched the Specialised Register (last searched May 2013) and CENTRAL
      (2013, Issue 4). SELECTION CRITERIA: Randomised clinical trials in which LMWH
      given once daily is compared with LMWH given twice daily for the initial
      treatment of VTE. DATA COLLECTION AND ANALYSIS: Two review authors assessed
      trials for inclusion and extracted data independently. MAIN RESULTS: Five studies
      were included with a total of 1508 participants. The pooled data showed no
      statistically significant difference in recurrent VTE between the two treatment
      regimens (OR 0.82, 0.49 to 1.39; P = 0.47). A comparison of major haemorrhagic
      events (OR 0.77, 0.40 to 1.45; P = 0.41), improvement of thrombus size (OR 1.41,
      0.66 to 3.01; P = 0.38) and mortality (OR 1.14, 0.62 to 2.08; P = 0.68) also
      showed no statistically significant differences between the two treatment
      regimens. None of the five included studies reported data on post-thrombotic
      syndrome. AUTHORS' CONCLUSIONS: Once daily treatment with LMWH is as effective
      and safe as twice daily treatment with LMWH.

PMID- 23857563
TI  - Interventions to encourage uptake of cancer screening for people with severe
      mental illness.
AB  - BACKGROUND: Adults with severe mental illness (i.e. schizophrenia or other
      related psychotic disorders and bipolar disorder) can be at greater risk of
      cancer than those without severe mental illness (SMI). Early detection of cancer
      through screening is effective in improving patient outcomes including death.
      However, people with SMI are less likely than others to take up available cancer
      screening. OBJECTIVES: To determine the effectiveness of interventions targeted
      at adults with SMI, or their carers or health professionals, and aimed at
      increasing the uptake of cancer screening tests for which the adults with SMI are
      eligible. SEARCH METHODS: We searched electronically the Cochrane Schizophrenia
      Group's Register (25th October 2012). SELECTION CRITERIA: All randomised
      controlled trials (RCTs) of interventions, targeted towards adults with SMI or
      their carers or health professionals, to encourage uptake of cancer screening
      tests for which the adults with SMI were eligible. DATA COLLECTION AND ANALYSIS:
      Two review authors independently screened titles and abstracts and assessed these
      against the inclusion criteria. MAIN RESULTS: We did not find any trials that met
      the inclusion criteria. AUTHORS' CONCLUSIONS: A comprehensive search showed that
      currently there is no RCT evidence for any method of encouraging cancer screening
      uptake in people with SMI. No specific approach can therefore be recommended.
      High-quality, large-scale RCTs are needed urgently to help address the disparity
      between people with SMI and others in cancer screening uptake.

PMID- 23857564
TI  - Development and optimization of the determination of pharmaceuticals in water
      samples by SPE and HPLC with diode-array detection.
AB  - This paper describes the development, optimization, and validation of a method
      for the determination of five pharmaceuticals from different therapeutic classes
      (antibiotics, anthelmintics, glucocorticoides) in water samples. Water samples
      were prepared using SPE and extracts were analyzed by HPLC with diode-array
      detection. The efficiency of 11 different SPE cartridges to extract the
      investigated compounds from water was tested in preliminary experiments. Then,
      the pH of the water sample, elution solvent, and sorbent mass were optimized.
      Except for optimization of the SPE procedure, selection of the optimal HPLC
      column with different stationary phases from different manufacturers has been
      performed. The developed method was validated using spring water samples spiked
      with appropriate concentrations of pharmaceuticals. Good linearity was obtained
      in the range of 2.4-200 MUg/L, depending on the pharmaceutical with the
      correlation coefficients >0.9930 in all cases, except for ciprofloxacin (0.9866).
      Also, the method has revealed that low LODs (0.7-3.9 MUg/L), good precision
      (intra- and interday) with RSD below 17% and recoveries above 98% for all
      pharmaceuticals. The method has been successfully applied to the analysis of
      production wastewater samples from the pharmaceutical industry.

PMID- 23857565
TI  - Discrete spherical hexadecavanadates incorporating a bromide with oxidative
      bromination activity.
AB  - Two discrete hexadecavanadates, (n-Bu4N)4[V16O38(X)] (X = Cl(-) (1) and X = Br(-)
      (2)), were synthesized by a reaction of [V10O26](4-) with a template anion
      resulting in the incorporation of chloride or bromide in the {V16} spherical
      cluster framework. The reaction of [V10O26](4-) with p-toluenesulfonic acid
      proceeded under an aerobic environment to give 2 in the presence of an excess
      amount of bromide anion, which acted as both a template anion and a reducing
      reagent for the formation of the mixed-valence framework. For the synthesis of
      cluster 1, additional reductive conditions were required due to the weak reducing
      ability of the chloride anion. The crystal structures of 1 and 2 were determined
      using single-crystal X-ray diffraction analysis. Both were found to consist of a
      discrete [V(V)9V(IV)7O38(X)](4-) framework by the linkage of VO5 pyramidal units.
      Cyclic voltammetric studies of 1 and 2 in acetonitrile showed a series of
      stepwise reversible redox processes, which were due to the redox of the spherical
      polyoxovanadate frameworks. The oxidative bromination reactions of aromatic
      substrates were also investigated using cluster 2 as a catalyst under aerobic
      conditions.

PMID- 23857567
TI  - Medical education: part of the problem and part of the solution.
AB  - Medical education today is pedagogically superb, but the graduates of our
      educational programs are still unable to successfully translate decades of
      biomedical advances into health care that reliably meets the Institute of
      Medicine quality criteria. Realizing the promise of high-quality health care will
      require that medical educators accept that they must fulfill their contract with
      society to reduce the burden of suffering and disease through the education of
      physicians. Educational redesign must begin with the understanding that the
      professional identity of the physician who was successful in the acute disease
      era of the 20th century will not be effective in the complex chronic disease era
      of the 21st century. Medical schools and residency programs must restructure
      their views of basic and clinical science and workplace learning to give equal
      emphasis to the science and skills needed to practice in and lead in complex
      systems. They must also rethink their relationships with clinical environments so
      that the education of students and residents accelerates the transformation in
      health care delivery needed to fulfill our contract with society. 

PMID- 23857566
TI  - Automatic particle detection in microscopy using temporal correlations.
AB  - One of the fundamental problems in the analysis of single particle tracking data
      is the detection of individual particle positions from microscopy images.
      Distinguishing true particles from noise with a minimum of false positives and
      false negatives is an important step that will have substantial impact on all
      further analysis of the data. A common approach is to obtain a plausible set of
      particles from a larger set of candidate particles by filtering using manually
      selected threshold values for intensity, size, shape, and other parameters
      describing a particle. This introduces subjectivity into the analysis and hinders
      reproducibility. In this paper, we introduce a method for automatic selection of
      these threshold values based on maximizing temporal correlations in particle
      count time series. We use Markov Chain Monte Carlo to find the threshold values
      corresponding to the maximum correlation, and we study several experimental data
      sets to assess the performance of the method in practice by comparing manually
      selected threshold values from several independent experts with automatically
      selected threshold values. We conclude that the method produces useful results,
      reducing subjectivity and the need for manual intervention, a great benefit being
      its easy integratability into many already existing particle detection
      algorithms.

PMID- 23857568
TI  - A novel c.776_777insA mutation in CLN1 leads to infantile neuronal ceroid
      lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses are the most common autosomal recessive
      neurodegenerative disorders in children, with a worldwide incidence of 1 in
      100,000 live births. Multiple clinical variants are caused by more than 400
      mutations in at least 14 different genes. These progressive genetic disorders
      primarily manifest in the central nervous system because of an extensive loss of
      neurons, specifically in the cerebral and cerebellar cortices. Patients with
      mutations in CLN1, which encodes palmitoyl-protein thioesterase 1 (PPT1),
      primarily manifest with infantile neuronal ceroid lipofuscinosis (Haltia
      Santavuori disease). Affected children usually present between 1 and 2 years of
      age and typically die by 8 to 13 years of age. We describe a patient with
      infantile neuronal ceroid lipofuscinosis with a novel c.776_777insA mutation in
      CLN1. This insertion induces a frameshift and a premature stop codon late within
      the CLN1 messenger RNA (mRNA) transcript which is likely recognized by nonsense
      mediated translation repression, decreasing PPT1 abundance.

PMID- 23857569
TI  - A review of local antibiotic implants and applications to veterinary orthopaedic
      surgery.
AB  - In the face of increasing incidence of multi-drug resistant implant infections,
      local antibiotic modalities are receiving increased attention for both infection
      prophylaxis and treatment. Local antibiotic therapy that achieves very high
      antibiotic drug concentrations at the site of the implant may represent an avenue
      for treatment of biofilm-forming bacterial pathogens. Randomized controlled
      trials in human patients have demonstrated an infection risk reduction when
      antibiotic-impregnated cement is used for infection prophylaxis in implanted
      joint prostheses, and when a gentamicin-impregnated collagen sponge is used for
      infection prophylaxis in midline sternotomy. The other modalities discussed have
      for the most part yet to be evaluated in randomized controlled trials in
      veterinary or human patients. In general, the in vivo pharmacokinetics and
      appropriate dosing profiles for local antibiotic modalities have yet to be
      elucidated. Toxicity is possible, and attention to the dose applied is warranted.

PMID- 23857570
TI  - Outcome following removal of TPLO implants with surgical site infection.
AB  - OBJECTIVE: To evaluate the outcome of surgical site infection (SSI) associated
      with tibial plateau levelling osteotomy (TPLO) implants following treatment by
      medical management alone or implant removal with or without the administration of
      antibiotic medication. ANIMALS: Ninety dogs (104 TPLO surgical procedures).
      METHODS: Records of dogs that had undergone TPLO implant removal due to SSI were
      reviewed. Outcome following treatment with antibiotic medications without implant
      removal, and treatment with implant removal with and without the administration
      of antibiotic medications was evaluated. RESULTS: Treatment of SSI with
      antibiotic medication alone failed in 88.9% (64/72) of the dogs. The clinical
      signs of SSI resolved in 94.9% (74/78) of the dogs treated with implant removal
      (with and without the administration of antibiotic medication post-implant
      removal). The effect of administration of antibiotic medication on outcome of
      treatment of the SSI by implant removal was not significant. The rate of SSI
      associated with the Synthes implant was higher than with the Slocum implant, but
      not the New Generation implant. CONCLUSION: Implant removal with or without the
      administration of antibiotic medication post-implant removal for treatment of
      TPLO SSI provided superior outcome compared to treatment with antibiotic
      medications without implant removal. CLINICAL SIGNIFICANCE: Implant removal
      should be considered for TPLO SSI that have not responded to appropriate medical
      management. Further investigation of the various TPLO implants and their effects
      on postoperative infection rate is warranted.

PMID- 23857571
TI  - The effects of a novel lateral extracapsular suture system on the kinematics of
      the cranial cruciate deficient canine stifle.
AB  - OBJECTIVE: To evaluate the relative position of the femur and tibia in cranial
      cruciate ligament-intact stifles, cranial cruciate ligament-deficient stifles,
      and cruciate-deficient stifles following lateral extracapsular suture system
      (LESS) stabilization under load at specific joint angles. STUDY DESIGN: In vitro
      biomechanical study. METHODS: Twenty pelvic limbs from 11 dogs were used to
      evaluate the relative position of the femur and tibia between three stifle
      conditions (cranial cruciate ligament-intact, cranial cruciate ligament
      deficient, and LESS-stabilized) at a load of 30% of body weight and stifle angles
      of 125 degrees , 135 degrees , and 145 degrees  using electromagnetic tracking
      sensors. RESULTS: Cranial cruciate ligament-deficient stifles had significantly
      greater (p <0.0001) cranial displacement and internal rotation of the tibia
      relative to the femur than cranial cruciate ligament-intact or LESS stifles at
      all stifle angles. Cranial displacement of the tibia relative to the femur for
      cranial cruciate ligament-intact and LESS stifles were not significantly
      different from one another at a stifle angle of 125 degrees , but were
      significantly different at stifle angles of 135 degrees  (p = 0.0182) and 145
      degrees  (p = 0.0012). There was no significant difference in internal rotation
      of the tibia relative to the femur between the cranial cruciate ligament-intact
      and LESS stifles at any of the stifle angles. CLINICAL SIGNIFICANCE: The LESS
      procedure effectively decreased cranial tibial displacement and eliminated
      internal rotation of the tibia relative to the femur in the cranial cruciate
      ligament-deficient stifles at stifle angles of 125 degrees , 135 degrees , and
      145 degrees  in vitro.

PMID- 23857572
TI  - Clinical audit for the tibial tuberosity advancement procedure: establishing the
      learning curve and monitoring ongoing performance for the tibial tuberosity
      advancement procedure using the cumulative summation technique.
AB  - OBJECTIVES: To quantitatively assess the learning curve for the tibial tuberosity
      advancement (TTA) procedure performed by a single surgeon using the cumulative
      summation (CUSUM) technique and to determine if surgeon performance remained
      under control (i.e. within specified quality boundaries) after the learning curve
      had been climbed. STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n = 122) with
      cranial cruciate ligament deficient stifles (n = 167). METHODS: Records of all
      dogs that had a TTA procedure performed by the same surgeon were reviewed. Cases
      were included if the following information was available: weight, breed, date of
      surgery, presence of partial or full cruciate rupture, meniscal pathology,
      occurrence and description of postoperative complications and treatment with a
      minimum of 12 months follow-up. Patients were excluded if they had a concurrent
      illness. Major complications were defined as those requiring revision surgery.
      The CUSUM technique was used to determine the time taken for the surgeon to reach
      a pre-defined level of competency and to monitor ongoing performance. RESULTS:
      Major complications occurred in 15 out of 167 procedures (9%) within 12 months of
      TTA surgery. The complication rate decreased as surgical experience was gained
      with the technique, however the learning curve continued until the 22nd
      procedure. Thereafter, despite the target complication rate being re-set at a
      lower level, the surgeon's performance remained acceptable, i.e. within the
      revised quality boundary. CLINICAL SIGNIFICANCE: The CUSUM technique was used for
      clinical audit, to determine the learning curve for the TTA procedure for a
      single surgeon, and to monitor ongoing performance. An experienced general
      practitioner had a learning curve of 22 procedures and complication rates were
      within the published ranges.

PMID- 23857573
TI  - Surgical treatment of distal tarsal joint luxations in three horses.
AB  - The clinical signs, radiographic findings, surgical treatment, and outcome of
      three horses with luxation of the distal tarsal joints are reported. Two patients
      showed luxations of the tarsometatarsal joint whereas luxation of the proximal
      intertarsal joint was found in one case. Open reduction, followed by internal
      fixation was performed in two horses and closed reduction with a transfixation
      pin cast was performed in the third. The treatment in all three cases resulted in
      a satisfactory clinical outcome. 

PMID- 23857574
TI  - Far lateral lumbar disc extrusion: MRI findings and surgical treatment.
AB  - This case report describes the magnetic resonance imaging (MRI) findings and the
      treatment of a far lateral extrusion of disc material at the sixth and seventh
      lumbar vertebrae (L6-L7) in a five-year-old male Alpine Dachsbracke dog referred
      to our hospital for investigation of the complaint of a one week progressive
      lameness in the left pelvic limb and poorly localized back pain. An extra
      foraminal left lateral disc herniation impinging on the sixth lumbar nerve root
      was diagnosed by MRI examinations. Due to the far lateral position of the
      extruded disc material on MRI, surgical opening of the spinal canal was not
      necessary. Removal of the herniated soft disc material impinging on the L6 nerve
      root, and fenestration of the L6-L7 disc was performed laterally. To the author's
      knowledge 'far-lateral' disc herniation beyond the neuroforamen without any
      spinal canal contact has not been described in dogs until now. A complete
      recovery with no evidence of pain was achieved only after a couple of weeks after
      surgery. We acknowledge that it is possible that other pathological mechanisms
      may have contributed to clinical signs and to a delayed recovery. 

PMID- 23857575
TI  - Traumatic fibrotic myopathy of the tensor fascia lata muscle in a Whippet.
AB  - A two-year-old female neutered Whippet was referred for evaluation of progressive
      right pelvic limb lameness. Clinical examination revealed a fibrous band palpable
      along the cranial aspect of the quadriceps muscle group, and signs of discomfort
      on extension of the right hip. Computed tomography and ultrasonographic
      examination revealed mineralization of the tensor fascia lata muscle with
      enthesophytosis of its origin. Surgical exploration confirmed a fibrous band
      affecting the cranial border of the tensor fascia lata muscle. Resection of the
      band resulted in complete resolution of clinical signs. Histopathology was
      consistent with a fibrotic myopathy. To the authors' knowledge, this is the first
      case of a fibrotic myopathy affecting the tensor fascia lata muscle in the dog. 

PMID- 23857577
TI  - The challenge of isometry for extracapsular devices.

PMID- 23857578
TI  - Bone infection.

PMID- 23857579
TI  - Work-function modification of Au and Ag surfaces upon deposition of self
      assembled monolayers: influence of the choice of the theoretical approach and the
      thiol decomposition scheme.
AB  - We have characterized theoretically the work-function modifications of the (111)
      surfaces of gold and silver upon deposition of self-assembled monolayers based on
      methanethiol and trifluoromethanethiol. A comparative analysis is made between
      the experimental results and those obtained from two widely used approaches based
      on density functional theory. The contributions to the total work-function
      modifications are estimated on the basis of two decomposition schemes of the
      thiol molecules that have been proposed in the literature. The contributions are
      found to differ significantly between the two approaches, as do the corresponding
      adsorption energies. 

PMID- 23857580
TI  - Micellar electrokinetic chromatography-electrospray ionization mass spectrometry
      employing a volatile surfactant for the analysis of amino acids in human urine.
AB  - A new MEKC-ESI-MS method for the analysis of amino acids (AAs) in human urine was
      developed employing ammonium perfluorooctanoate (APFO) as volatile surfactant.
      The influence of APFO on the MS signal of AAs was evaluated by infusion
      experiments, which showed that APFO hardly affects analyte responses and presents
      significantly less ion suppression than equal concentrations of ammonium acetate.
      In order to obtain efficient separation of AAs, MEKC parameters such as the pH
      and APFO concentration of the BGE, were optimized. Optimum AA resolution,
      including baseline separation of leucine and isoleucine, was obtained using 150
      mM APFO (pH 9.0) as BGE, representing a considerable selectivity improvement over
      CE using 50 mM ammonium acetate (pH 9.0). Optimization of CE-MS parameters, such
      as sheath liquid composition and flow rate, and ESI and MS settings, led to LODs
      ranging from 9 to 26 ng/mL for the 20 tested AAs, which is highly favorable for
      an MEKC-MS method. Good linearity (r(2) > 0.99) and repeatability were obtained
      for all AAs tested with RSD values of 3.0-6.7% for peak area and <1.5% for
      migration time. The applicability of the MEKC-MS method was demonstrated by the
      quantitative determination of AAs in urine employing only a 1:1 dilution with BGE
      as sample pretreatment. All AAs could selectively be detected and quantified
      obtaining relevant concentration values for normal human urine. 

PMID- 23857581
TI  - Macromolecular composition dictates receptor and G protein selectivity of
      regulator of G protein signaling (RGS) 7 and 9-2 protein complexes in living
      cells.
AB  - Regulator of G protein signaling (RGS) proteins play essential roles in the
      regulation of signaling via G protein-coupled receptors (GPCRs). With hundreds of
      GPCRs and dozens of G proteins, it is important to understand how RGS regulates
      selective GPCR-G protein signaling. In neurons of the striatum, two RGS proteins,
      RGS7 and RGS9-2, regulate signaling by MU-opioid receptor (MOR) and dopamine D2
      receptor (D2R) and are implicated in drug addiction, movement disorders, and
      nociception. Both proteins form trimeric complexes with the atypical G protein
      beta subunit Gbeta5 and a membrane anchor, R7BP. In this study, we examined
      GTPase-accelerating protein (GAP) activity as well as Galpha and GPCR selectivity
      of RGS7 and RGS9-2 complexes in live cells using a bioluminescence resonance
      energy transfer-based assay that monitors dissociation of G protein subunits. We
      showed that RGS9-2/Gbeta5 regulated both Gi and Go with a bias toward Go, but
      RGS7/Gbeta5 could serve as a GAP only for Go. Interestingly, R7BP enhanced GAP
      activity of RGS7 and RGS9-2 toward Go and Gi and enabled RGS7 to regulate Gi
      signaling. Neither RGS7 nor RGS9-2 had any activity toward Gz, Gs, or Gq in the
      absence or presence of R7BP. We also observed no effect of GPCRs (MOR and D2R) on
      the G protein bias of R7 RGS proteins. However, the GAP activity of RGS9-2 showed
      a strong receptor preference for D2R over MOR. Finally, RGS7 displayed an four
      times greater GAP activity relative to RGS9-2. These findings illustrate the
      principles involved in establishing G protein and GPCR selectivity of striatal
      RGS proteins. 

PMID- 23857582
TI  - Heterogeneous nuclear ribonucleoprotein (HnRNP) K genome-wide binding survey
      reveals its role in regulating 3'-end RNA processing and transcription
      termination at the early growth response 1 (EGR1) gene through XRN2 exonuclease.
AB  - The heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid-binding
      protein that acts as a docking platform integrating signal transduction pathways
      to nucleic acid-related processes. Given that hnRNPK could be involved in other
      steps that compose gene expression the definition of its genome-wide occupancy is
      important to better understand its role in transcription and co-transcriptional
      processes. Here, we used chromatin immunoprecipitation followed by deep
      sequencing (ChIP-Seq) to analyze the genome-wide hnRNPK-DNA interaction in colon
      cancer cell line HCT116. 9.1/3.6 and 7.0/3.4 million tags were sequenced/mapped,
      then 1809 and 642 hnRNPK binding sites were detected in quiescent and 30-min
      serum-stimulated cells, respectively. The inspection of sequencing tracks
      revealed inducible hnRNPK recruitment along a number of immediate early gene
      loci, including EGR1 and ZFP36, with the highest densities present at the
      transcription termination sites. Strikingly, hnRNPK knockdown with siRNA resulted
      in increased pre-RNA levels transcribed downstream of the EGR1 polyadenylation
      (A) site suggesting altered 3'-end pre-RNA degradation. Further ChIP survey of
      hnRNPK knockdown uncovered decreased recruitment of the 5'-3' exonuclease XRN2
      along EGR1 and downstream of the poly(A) signal without altering RNA polymerase
      II density at these sites. Immunoprecipitation of hnRNPK and XRN2 from intact and
      RNase A-treated nuclear extracts followed by shotgun mass spectrometry revealed
      the presence of hnRNPK and XRN2 in the same complexes along with other
      spliceosome-related proteins. Our data suggest that hnRNPK may play a role in
      recruitment of XRN2 to gene loci thus regulating coupling 3'-end pre-mRNA
      processing to transcription termination. 

PMID- 23857583
TI  - Estrogen receptor beta (ERbeta1) transactivation is differentially modulated by
      the transcriptional coregulator Tip60 in a cis-acting element-dependent manner.
AB  - Estrogen receptor (ER) beta1 and ERalpha have overlapping and distinct functions
      despite their common use of estradiol as the physiological ligand. These
      attributes are explained in part by their differential utilization of
      coregulators and ligands. Although Tip60 has been shown to interact with both
      receptors, its regulatory role in ERbeta1 transactivation has not been defined.
      In this study, we found that Tip60 enhances transactivation of ERbeta1 at the AP
      1 site but suppresses its transcriptional activity at the estrogen-response
      element (ERE) site in an estradiol-independent manner. However, different
      estrogenic compounds can modify the Tip60 action. The corepressor activity of
      Tip60 at the ERE site is abolished by diarylpropionitrile, genistein, equol, and
      bisphenol A, whereas its coactivation at the AP-1 site is augmented by
      fulvestrant (ICI 182,780). GRIP1 is an important tethering mediator for ERs at
      the AP-1 site. We found that coexpression of GRIP1 synergizes the action of
      Tip60. Although Tip60 is a known acetyltransferase, it is unable to acetylate
      ERbeta1, and its coregulatory functions are independent of its acetylation
      activity. In addition, we showed the co-occupancy of ERbeta1 and Tip60 at ERE and
      AP-1 sites of ERbeta1 target genes. Tip60 differentially regulates the endogenous
      expression of the target genes by modulating the binding of ERbeta1 to the cis
      regulatory regions. Thus, we have identified Tip60 as the first dual-function
      coregulator of ERbeta1. 

PMID- 23857584
TI  - FcgammaR-driven release of IL-6 by macrophages requires NOX2-dependent production
      of reactive oxygen species.
AB  - Activation of the FcgammaR via antigen containing immune complexes can lead to
      the generation of reactive oxygen species, which are potent signal transducing
      molecules. However, whether ROS contribute to FcgammaR signaling has not been
      studied extensively. We set out to elucidate the role of NADPH oxidase-generated
      ROS in macrophage activation following FcgammaR engagement using antigen
      containing immune complexes. We hypothesized that NOX2 generated ROS is necessary
      for propagation of downstream FcgammaR signaling and initiation of the innate
      immune response. Following exposure of murine bone marrow-derived macrophages
      (BMDMs) to inactivated Francisella tularensis (iFt)-containing immune complexes,
      we observed a significant increase in the innate inflammatory cytokine IL-6 at 24
      h compared with macrophages treated with Ft LVS-containing immune complexes.
      Ligation of the FcgammaR by opsonized Ft also results in significant ROS
      production. Macrophages lacking the gp91(phox) subunit of NOX2 fail to produce
      ROS upon FcgammaR ligation, resulting in decreased Akt phosphorylation and a
      reduction in the levels of IL-6 compared with wild type macrophages. Similar
      results were seen following infection of BMDMs with catalase deficient Ft that
      fail to scavenge hydrogen peroxide. In conclusion, our findings demonstrate that
      ROS participate in elicitation of an effective innate immune in response to
      antigen-containing immune complexes through FcgammaR. 

PMID- 23857585
TI  - Hepatitis C virus NS5A inhibits mixed lineage kinase 3 to block apoptosis.
AB  - Hepatitis C virus (HCV) infection results in the activation of numerous stress
      responses including oxidative stress, with the potential to induce an apoptotic
      state. Previously we have shown that HCV attenuates the stress-induced, p38MAPK
      mediated up-regulation of the K(+) channel Kv2.1, to maintain the survival of
      infected cells in the face of cellular stress. We demonstrated that this effect
      was mediated by HCV non-structural 5A (NS5A) protein, which impaired p38MAPK
      activity through a polyproline motif-dependent interaction, resulting in
      reduction of phosphorylation activation of Kv2.1. In this study, we investigated
      the host cell proteins targeted by NS5A to mediate Kv2.1 inhibition. We screened
      a phage-display library expressing the entire complement of human SH3 domains for
      novel NS5A-host cell interactions. This analysis identified mixed lineage kinase
      3 (MLK3) as a putative NS5A interacting partner. MLK3 is a serine/threonine
      protein kinase that is a member of the MAPK kinase kinase (MAP3K) family and
      activates p38MAPK. An NS5A-MLK3 interaction was confirmed by co
      immunoprecipitation and Western blot analysis. We further demonstrate a novel
      role of MLK3 in the modulation of Kv2.1 activity, whereby MLK3 overexpression
      leads to the up-regulation of channel activity. Accordingly, coexpression of NS5A
      suppressed this stimulation. Additionally we demonstrate that overexpression of
      MLK3 induced apoptosis, which was also counteracted by NS5A. We conclude that
      NS5A targets MLK3 with multiple downstream consequences for both apoptosis and
      K(+) homeostasis. 

PMID- 23857586
TI  - Zinc finger protein 64 promotes Toll-like receptor-triggered proinflammatory and
      type I interferon production in macrophages by enhancing p65 subunit activation.
AB  - The molecular mechanisms that fine-tune the Toll-like receptor (TLR)-triggered
      innate immune response need further investigation. As an important transcription
      factor, zinc finger proteins (ZFPs) play important roles in many cell functions,
      including development, differentiation, tumorigenesis, and functions of the
      immune system. However, the role of ZFP members in the innate immune responses
      remains unclear. Here we showed that the expression of C2H2-type ZFP, ZFP64, was
      significantly up-regulated in macrophages upon stimulation with TLR ligands,
      including LPS, CpG oligodeoxynucleotides, or poly(I:C). ZFP64 overexpression
      promoted TLR-triggered TNF-alpha, IL-6, and IFN-beta production in macrophages.
      Coincidently, knockdown of ZFP64 expression significantly inhibited the
      production of the above cytokines. However, activation of MAPK and IRF3 was not
      responsible for the ZFP64-mediated promotion of cytokine production.
      Interestingly, ZFP64 significantly up-regulated TLR-induced NF-kappaB activation.
      ZFP64 could bind to the promoter of the TNF-alpha, IL-6, and IFN-beta genes in
      macrophages only after TLR ligation. Furthermore, ZFP64 associated with the NF
      kappaB p65 subunit upon LPS stimulation, and TLR-ligated macrophages showed a
      lower level of p65 recruitment to the TNF-alpha, IL-6, and IFN-beta gene promoter
      in the absence of ZFP64. The data identify ZFP64 as a downstream positive
      regulator of TLR-initiated innate immune responses by associating with the NF
      kappaB p65 subunit, enhancing p65 recruitment to the target gene promoters and
      increasing p65 activation and, thus, leading to the promotion of TLR-triggered
      proinflammatory cytokine and type I interferon production. Our findings add
      mechanistic insight into the efficient activation of the TLR innate response
      against invading pathogens. 

PMID- 23857587
TI  - Characterization of a nitrite reductase involved in nitrifier denitrification.
AB  - Nitrifier denitrification is the conversion of nitrite to nitrous oxide by
      ammonia-oxidizing organisms. This process, which is distinct from
      denitrification, is active under aerobic conditions in the model nitrifier
      Nitrosomonas europaea. The central enzyme of the nitrifier dentrification pathway
      is a copper nitrite reductase (CuNIR). To understand how a CuNIR, typically
      inactivated by oxygen, functions in this pathway, the enzyme isolated directly
      from N. europaea (NeNIR) was biochemically and structurally characterized. NeNIR
      reduces nitrite at a similar rate to other CuNIRs but appears to be oxygen
      tolerant. Crystal structures of oxidized and reduced NeNIR reveal a substrate
      channel to the active site that is much more restricted than channels in typical
      CuNIRs. In addition, there is a second fully hydrated channel leading to the
      active site that likely acts a water exit pathway. The structure is minimally
      affected by changes in pH. Taken together, these findings provide insight into
      the molecular basis for NeNIR oxygen tolerance. 

PMID- 23857588
TI  - Rational design of multifunctional upconversion nanocrystals/polymer
      nanocomposites for cisplatin (IV) delivery and biomedical imaging.
AB  - By combining upconversion nanoparticles with the cisplatin (IV) prodrug we have
      demonstrated that a stable and multifunctional drug delivery system can be
      designed that will both reduce the drawbacks of cisplatin and give insight in to
      its in vitro/in vivo imaging. The up/down-conversion fluorescence are detectable
      and show obvious co-localization, demonstrating that the nanoparticles are rather
      stable inside cells and retain the UCNPs and block copolymer. 

PMID- 23857589
TI  - A conceptual and methodological framework for investigating etiologic
      heterogeneity.
AB  - Cancer has traditionally been studied using the disease site of origin as the
      organizing framework. However, recent advances in molecular genetics have begun
      to challenge this taxonomy, as detailed molecular profiling of tumors has led to
      discoveries of subsets of tumors that have profiles that possess distinct
      clinical and biological characteristics. This is increasingly leading to research
      that seeks to investigate whether these subtypes of tumors have distinct
      etiologies. However, research in this field has been opportunistic and anecdotal,
      typically involving the comparison of distributions of individual risk factors
      between tumors classified on the basis of candidate tumor characteristics. The
      purpose of this article is to place this area of investigation within a more
      general conceptual and analytic framework, with a view to providing more
      efficient and practical strategies for designing and analyzing epidemiologic
      studies to investigate etiologic heterogeneity. We propose a formal definition of
      etiologic heterogeneity and show how classifications of tumor subtypes with
      larger etiologic heterogeneities inevitably possess greater disease risk
      predictability overall. We outline analytic strategies for estimating the degree
      of etiologic heterogeneity among a set of subtypes and for choosing subtypes that
      optimize the heterogeneity, and we discuss technical challenges that require
      further methodologic research. We illustrate the ideas by using a pooled case
      control study of breast cancer classified by expression patterns of genes known
      to define distinct tumor subtypes.

PMID- 23857591
TI  - Pastoral care in old age psychiatry: addressing the spiritual needs of inpatients
      in an acute aged mental health unit.
AB  - INTRODUCTION: Pastoral Care (PC) practitioners respond to the spiritual needs of
      patients and families of all spiritual orientations. The integrated PC service in
      an acute psychogeriatric inpatient ward at St Vincent's Aged Mental Health
      Service, Melbourne, Australia, was examined to investigate how PC was being
      accessed by inpatients. METHODS: A retrospective medical record file audit was
      undertaken of patients admitted over a 16-month period from 1 February 2009 to 30
      June 30 2010 (n = 202). RESULTS: Sixty-eight percent were seen by PC
      practitioners during their admission. Sixty-six percent received PC assessments,
      32% received PC ministry, and 10% received PC ritual or worship interventions.
      Other interventions (counseling/education, crisis situation, grief/ bereavement
      counseling) occurred infrequently. Seventy-five percent of Roman Catholic
      patients received PC compared to 57% of those patients with no religious
      affiliation. However, the overall association between religious grouping and
      receiving PC was not significant. Gender, religion, marital status, legal status,
      country of birth, language spoken, living situation, carer needs, or educational
      level were not related to PC contact. Whether or not an inpatient received PC
      assessment was unrelated to diagnostic category. Patients seen by PC were
      significantly more likely to engage in religious practice, have longer length of
      stay, and have neuropsychological, social work and occupational therapy
      assessments. DISCUSSION: Results suggest that PC practitioners can help optimize
      the clinical care of patients by developing a comprehensive understanding of
      their spiritual and religious needs and providing a more holistic service.

PMID- 23857592
TI  - Psychosocial interventions for patients with head and neck cancer.
AB  - BACKGROUND: A diagnosis of head and neck cancer, like many other cancers, can
      lead to significant psychosocial distress. Patients with head and neck cancer can
      have very specific needs, due to both the location of their disease and the
      impact of treatment, which can interfere with basic day-to-day activities such as
      eating, speaking and breathing. There is a lack of clarity on the effectiveness
      of the interventions developed to address the psychosocial distress experienced
      by patients living with head and neck cancer. OBJECTIVES: To assess the
      effectiveness of psychosocial interventions to improve quality of life and
      psychosocial well-being for patients with head and neck cancer. SEARCH METHODS:
      We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register;
      the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE;
      CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP
      and additional sources for published and unpublished trials. The date of the most
      recent search was 17 December 2012. SELECTION CRITERIA: We selected randomised
      controlled trials and quasi-randomised controlled trials of psychosocial
      interventions for adults with head and neck cancer. For trials to be included the
      psychosocial intervention had to involve a supportive relationship between a
      trained helper and individuals diagnosed with head and neck cancer. Outcomes had
      to be assessed using a validated quality of life or psychological distress
      measure, or both. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected trials, extracted data and assessed the risk of bias, with mediation
      from a third author where required. Where possible, we extracted outcome measures
      for combining in meta-analyses. We compared continuous outcomes using either mean
      differences (MD) or standardised mean differences (SMD) and 95% confidence
      intervals (CI), with a random-effects model. We conducted meta-analyses for the
      primary outcome measure of quality of life and secondary outcome measures of
      psychological distress, including anxiety and depression. We subjected the
      remaining outcome measures (self esteem, coping, adjustment to cancer, body
      image) to a narrative synthesis, due to the limited number of studies evaluating
      these specific outcomes and the wide divergence of assessment tools used. MAIN
      RESULTS: Seven trials, totaling 542 participants, met the eligibility criteria.
      Studies varied widely on risk of bias, interventions used and outcome measures
      reported. From these studies, there was no evidence to suggest that psychosocial
      intervention promotes global quality of life for patients with head and neck
      cancer at end of intervention (MD 1.23, 95% CI -5.82 to 8.27) as measured by the
      European Organisation for Research and Treatment of Cancer Quality of Life
      Questionnaire (EORTC QLQ-C30). This quality of life tool includes five functional
      scales, namely cognitive, physical, emotional, social and role. There was no
      evidence to demonstrate that psychosocial intervention provides an immediate or
      medium-term improvement on any of these five functional scales. From the data
      available, there was no significant change in levels of anxiety (SMD -0.09, 95%
      CI -0.40 to 0.23) or depression following intervention (SMD -0.03, 95% CI -0.24
      to 0.19). At present, there is insufficient evidence to refute or support the
      effectiveness of psychosocial intervention for patients with head and neck
      cancer. AUTHORS' CONCLUSIONS: The evidence for psychosocial intervention is
      limited by the small number of studies, methodological shortcomings such as lack
      of power, difficulties with comparability between types of interventions and a
      wide divergence in outcome measures used. Future research should be targeted at
      patients who screen positive for distress and use validated outcome measures,
      such as the EORTC scale, as a measure of quality of life. These studies should
      implement interventions that are theoretically derived. Other shortcomings should
      be addressed in future studies, including using power calculations that may
      encourage multi-centred collaboration to ensure adequate sample sizes are
      recruited.

PMID- 23857590
TI  - Evaluation of coils for imaging histological slides: signal-to-noise ratio and
      filling factor.
AB  - PURPOSE: To investigate the relative gain in sensitivity of five histology coils
      designed in-house to accommodate tissue sections of various sizes and compare
      with commercial mouse head coils. METHODS: The coil set was tailored to house
      tissue sections ranging from 5 to1000 um encased in either glass slides or
      coverslips. RESULTS: Our simulations and experimental measurements demonstrated
      that although the sensitivity of this flat structure consistently underperforms
      relative to a birdcage head coil based on the gain expected from their respective
      filling factor ratios, our results demonstrate that it can still provide a
      remarkable gain in sensitivity. Our study also describes preparation protocols
      for freshly excised sections, as well as premounted tissue slides of both mouse
      and human specimens. Examples of the exceptional level of tissue detail and the
      near-perfect magnetic resonance imaging to light microscopic image coregistration
      are provided. CONCLUSION: The increase in filling factor achieved by the
      histology radiofrequency (RF) probe overcomes the losses associated with electric
      leaks inherent to this structure, leading to a 6.7-fold improvement in
      performance for the smallest coil implemented. Alternatively, the largest
      histology coil design exhibited equal sensitivity to the mouse head coil while
      nearly doubling the RF planar area coverage.

PMID- 23857593
TI  - An organizational approach to conflicts of interest: lessons from non-health care
      businesses.

PMID- 23857594
TI  - Autofluorescence removal using a customized filter set.
AB  - Quantitative fluorescence microscopy is severely hindered by intrinsic
      autofluorescence (AF). Endogenous fluorescent molecules in tissue and cell
      samples emit fluorescence that often dominates signals from specific dyes. This
      makes AF removal critical to the development and practice of quantitative
      fluorescence microscopy. In this study, we showed that AF signal could be
      separated from specific signal using a customized filter set. The filter set used
      the same excitation and beam splitter as the standard filter set, but the
      emission filter was red-shifted 40-60 nm from the peak of the specific dye. This
      filter set configuration collected mostly AF with minimum contribution from the
      specific dye. A linear transformation of AF images was required to correct for
      the difference in exposure and filter configuration. The constants (slope and
      intercept) in linear transformation were obtained through a pixel to pixel
      comparison between AF images (no staining) obtained by the standard filter set
      and the customized AF filter set. After staining of specific dye, the standard
      filter collecting target dye spectra was used to capture both target signal and
      AF, whereas customized filter was used to capture only AF. AF removal was
      accomplished by subtracting the linear transformed AF image from the image
      obtained from the standard filter. To validate our approach, we examined weak
      staining of androgen receptor in an AF abundant prostate tissue sample. Our
      method revealed a similar but cleaner nuclear staining of androgen receptor in a
      specimen, when compared to a traditional autofluorescence removal method.

PMID- 23857596
TI  - Anxiety and decreased social support underline poorer quality of life of parent
      living kidney donors.
AB  - INTRODUCTION: A growing body of published work suggests that the parent-child
      relationship can be inherently coercive, such that the expectation that a living
      parent will not hesitate to donate a kidney to their children, makes informed
      consent difficult if not impossible to ascertain. The present study was designed
      to explore whether the emotional response and social resources have a similar
      effect on health-related quality of life among parent and sibling living kidney
      donors. METHODS: This was a cross-sectional study. A total of 98 living kidney
      donors (60 parent donors, 38 sibling donors) completed an assessment including
      emotional response, social support and quality of life. RESULTS: Depression,
      anxiety, subjective social support and quality of life scores were much poorer
      for parent than sibling donors. Parent donors also showed more anxiety and poorer
      physical functioning than their counterparts in the general population.
      Hierarchical multiple regression analyses suggested that anxiety and decreased
      social support in the parent group were negatively associated with physical and
      mental function. In the sibling group, the main indicator of improved physical
      state was higher education level. DISCUSSION: Current results raised new concerns
      for the quality of life of parent donors as emotional response and social support
      differentially affected parent versus sibling quality of life. Therefore,
      stricter standards for physical selection, as well as emotional and supportive
      intervention, are needed for parent donors.

PMID- 23857595
TI  - Large-scale, three-dimensional, free-standing, and mesoporous metal oxide
      networks for high-performance photocatalysis.
AB  - Mesoporous nanostructures represent a unique class of photocatalysts with many
      applications, including splitting of water, degradation of organic contaminants,
      and reduction of carbon dioxide. In this work, we report a general Lewis acid
      catalytic template route for the high-yield producing single- and multi-component
      large-scale three-dimensional (3D) mesoporous metal oxide networks. The large
      scale 3D mesoporous metal oxide networks possess large macroscopic scale
      (millimeter-sized) and mesoporous nanostructure with huge pore volume and large
      surface exposure area. This method also can be used for the synthesis of large
      scale 3D macro/mesoporous hierarchical porous materials and noble metal
      nanoparticles loaded 3D mesoporous networks. Photocatalytic degradation of Azo
      dyes demonstrated that the large-scale 3D mesoporous metal oxide networks enable
      high photocatalytic activity. The present synthetic method can serve as the new
      design concept for functional 3D mesoporous nanomaterials. 

PMID- 23857597
TI  - Long-term outcome of laparoscopic ileocecal resection for Crohn's disease before
      the era of biologics.
AB  - BACKGROUND: Crohn's disease (CD) of the terminal ileum not responding to standard
      medical treatment is more and more treated with biologics instead of surgery. In
      order to get more information on the results of surgery, we analyzed the outcome
      of laparoscopic ileocecal resection (LICR) performed before the widespread use of
      these drugs. METHODS: Chart reviews and telephone follow-ups were performed on
      119 patients treated with laparoscopic ileocecal resection for CD. Follow-ups
      were performed at a median of 58 (17-124) and 113(69-164) months. Symptomatic
      restenosis requiring surgery or endoscopic dilatation was the primary endpoint.
      We further analyzed risk factors of recurrence. RESULTS: Of the 119 patients
      initially treated, 18 required surgery (n = 14) or endoscopic dilatation (n = 4).
      The calculated rates of re-intervention were 10 und 17.5 % at 5 and 10 years,
      respectively. Ninety percent of the patients had a Crohn-specific medication
      treatment at the time of surgery, but only 51.4 und 46.9 % at FU 1 und 2,
      respectively. Smoking increased the risk of recurrence (OR 3.7, P = 0.011).
      CONCLUSION: The data demonstrate excellent long-term results of LICR for CD of
      the terminal ileum. Surgery should be considered as a first choice treatment in
      many patients with ileocecal CD not responding to conventional treatment.

PMID- 23857598
TI  - Quality colonoscopy and risk of interval cancer in Lynch syndrome.
AB  - PURPOSE: Despite colonoscopic surveillance, Lynch syndrome patients develop
      colorectal cancer (CRC). Identification of modifiable factors has the potential
      to improve outcome of surveillance. The aims of this study were to determine (1)
      characteristics of patients with CRC, (2) endoscopic and histological features of
      these cancers, and (3) quality of the previous colonoscopy. METHODS:
      Approximately 2,200 medical reports from proven and obligate mutation carriers
      identified at the Dutch Lynch Syndrome Registry and two large hospitals were
      retrospectively analyzed for the presence of an interval cancer defined as CRC
      diagnosed within 24 months of previous colonoscopy. RESULTS: Thirty-one interval
      cancers were detected in 29 patients (median age of 52 [range 35-73]), after a
      median time of 17 months. All were MLH1 or MSH2 mutation carriers, and 39 % had a
      previous CRC. In patients without previous surgery for CRC, 84 % was proximally
      located. Of all interval cancers, 77 % were at local stage (T1-3N0Mx). In three
      patients (9 %) with an incomplete previous colonoscopy, CRC was located in the
      unexamined colon. In six of the nine patients with an adenoma during previous
      colonoscopy, the cancer was detected in the same colonic segment as the
      previously removed adenoma. CONCLUSIONS: Interval cancers were detected in MLH1
      and MSH2 mutation carriers, especially in those with a history of previous CRC
      and between 40 and 60 years. Interval cancer could be related to incompleteness
      of previous endoscopy and possibly residual adenomatous tissue. Further reduction
      of the interval cancer risk may be achieved by optimizing endoscopy quality and
      individualization of surveillance guidelines.

PMID- 23857599
TI  - The value of the pretreatment albumin/globulin ratio in predicting the long-term
      survival in colorectal cancer.
AB  - BACKGROUND: Low serum albumin was found as a predictor of long-term mortality in
      colorectal cancer (CRC) patients. Our aim was to evaluate the value of the
      pretreatment albumin/globulin ratio (AGR) to predict the long-term mortality in
      CRC patients. METHODS: Patients were included if they had comprehensive metabolic
      panel (CMP) before treatment (surgery or chemotherapy). The albumin/globulin
      ratio, routinely reported in CMP, is calculated [AGR = Albumin/(Total protein -
      Albumin)]. Patients were divided into three equal tertiles according to their
      pretreatment AGR. The primary outcome was cancer-related mortality, which was
      obtained from our cancer registry database. RESULTS: A total of 534 consecutive
      CRC patients had pretreatment CMP. The 1st AGR tertile had a significant higher 4
      year mortality compared to the second and third AGR tertiles (42 vs. 19 and 7 %,
      p < 0.0001 according to Fisher's exact two-tailed test). In the multivariate
      model, AGR remained an independent predictor of survival with 75 % decrease in
      mortality among the highest AGR tertile in comparison to the lowest AGR tertile,
      p < 0.0001. In the subset of 234 patients with normal serum albumin (albumin of
      >3.5 g/dl), serum AGR continues to be an independent predictor of cancer-related
      mortality with an adjusted hazard ratio of the third tertile compared to the
      first tertile equal to 0.05 (95 % confidence interval 0.01-0.33, p = 0.002).
      CONCLUSION: Low AGR was a strong independent predictor of long-term cancer
      specific survival among colorectal cancer patients. Additionally, among the
      patients with normal albumin (>3.5 g/dl), patients with lower globulins but
      higher albumin and AGR levels had better survival.

PMID- 23857600
TI  - Comparative method evaluation for size and size-distribution analysis of gold
      nanoparticles.
AB  - Gold nanoparticles (GNPs) are popular colloidal substrates in various sensor,
      imaging, and nanomedicine applications. In separation science, they have raised
      some interest as a support for sample preparation. Reasons for their popularity
      are their low cost, ability for size-controlled synthesis with well-defined
      narrow nanoparticle size distributions, as well as straightforward surface
      functionalization by self-assembling (thiol-containing) molecules on the surface,
      which allows flexible introduction of functionalities for the selective capture
      of analytes. Most commonly, the method of first choice for size determination is
      dynamic light scattering (DLS). However, DLS has some serious shortcomings, and
      results from DLS may be misleading. For this reason, in this contribution several
      distinct complementary nanoparticle sizing methodologies were utilized and
      compared to characterize citrate-capped GNPs of different diameters in the range
      of 13-26 nm. Weaknesses and strengths of DLS, transmission electron microscopy,
      asymmetrical-flow field-flow fractionation and nanoelectrospray gas-phase
      electrophoretic mobility molecular analysis are discussed and the results
      comparatively assessed. Furthermore, the distinct GNPs were characterized by
      measuring their zeta-potential and surface plasmon resonance spectra. Overall,
      the combination of methods for GNP characterization gives a more realistic and
      comprehensive picture of their real physicochemical properties, (hydrodynamic)
      diameter, and size distribution. 

PMID- 23857601
TI  - IL-17A stimulates the progression of giant cell tumors of bone.
AB  - PURPOSE: Giant cell tumors of bone (GCTB) exhibit aggressive bone lytic behavior.
      Studies have shown that interleukin 17A (IL-17A) is involved pathologic bone
      resorption in various skeletal disorders. Thus, we have investigated the role of
      IL-17A in GCTBs. EXPERIMENTAL DESIGN: We evaluated the progression of GCTBs using
      Campanacci grading and Enneking staging systems in 74 patients with GCTB. The
      expression of IL-17A and the IL-17A receptor A (IL-17RA) was assessed in GCTB
      tissues and in both multinucleated giant cells (MNGC) and stromal cells cultured
      in vitro using immunostaining and reverse transcription PCR (RT-PCR). The effects
      of IL-17A on the osteolytic activity of the MNGCs and the proliferation of the
      stromal cells were investigated using the "pit" formation and MTT assays,
      respectively. The effects of IL-17A on the expression of proosteolytic factors
      were examined in primary cultured MNGCs and stromal cells using RT-PCR, Western
      blotting, and gene expression microarrays. RESULTS: In GCTBs, we detected
      abundant levels of IL-17A, which were associated with tumor extension and grade.
      IL-17A is predominantly produced by MNGCs, whereas IL-17RA is expressed by both
      MNGCs and stromal cells in GCTBs. In the MNGCs, the IL-17A increased the mRNA
      expression of IL-17A and proosteolytic enzymes, and also enhanced osteolytic
      ability. In the stromal cells, the IL-17A stimulated cellular proliferation and
      the expression of proosteolytic factors, including RANKL through myc and STAT3,
      respectively. In addition, IL-17A stimulated in vivo tumor growth and the extent
      of angiogenesis in GCTBs. CONCLUSION: IL-17A stimulates the progression of GCTBs
      and might represent a useful candidate marker for progression and as a
      therapeutic target for GCTBs.

PMID- 23857602
TI  - Estrogen receptor alpha regulates ATM Expression through miRNAs in breast cancer.
AB  - PURPOSE: Estrogen receptor alpha (ERalpha) is an essential element regulating
      mammary gland development and it contributes to breast cancer development and
      progression. Most of the ER-negative breast cancers display more aggressive
      clinical behaviors and are resistant to antiestrogen therapies. In addition, many
      ER-negative tumors show insensitivity to many chemotherapeutic drugs and
      radiotherapy, although mechanisms underlying this phenotype are less clear.
      EXPERIMENTAL DESIGN: We conducted immunohistochemistry on 296 cases of breast
      cancer tissues using a variety of antibodies. On the basis of the clinical data,
      we conducted siRNA knockdown to study the role of ERalpha on ATM expression in
      breast cancer cell lines. Furthermore, we used antisense oligonucleotides against
      micro RNAs (miRNA) or miRNA overexpression plasmids to study the role of miR-18a
      and -106a on ATM expression. Finally we used in situ hybridization to assess miR
      18a and -106a expression in breast cancer tissues. RESULTS: We found that in ER
      negative breast cancer tissues, expression of the ATM kinase, a critical DNA
      damage-response protein, is aberrantly upregulated. We also found that the
      locoregional recurrence rate after radiotherapy positively correlates with ATM
      expression. On the cellular level, we showed that ERalpha, but not ERbeta,
      negatively regulates ATM expression. Furthermore, we identified that ERalpha
      activates miR-18a and -106a to downregulate ATM expression. We also showed that
      miR-18a and -106a were significantly underexpressed in ER-negative breast cancer
      tissues. CONCLUSIONS: We reveal a novel mechanism involving ERalpha and miR-18a
      and -106a regulation of ATM in breast cancer.

PMID- 23857603
TI  - The translocation t(4;14) can be present only in minor subclones in multiple
      myeloma.
AB  - PURPOSE: Although the translocation t(4;14) is supposed to be a primary event in
      multiple myeloma, we have been surprised to observe that in large relapse series
      of patients, the t(4;14) can be observed only in subpopulations of plasma cells,
      in contrast to what is seen at diagnosis. This observation raised the question of
      possible subclones harboring the translocation that would be observable only at
      the time of relapse. EXPERIMENTAL DESIGN: To address this issue, we analyzed by
      FISH a cohort of 306 patients for whom we had at least two samples obtained at
      different disease phases. RESULTS: We observed a "gain" of the t(4;14) in 14
      patients, and conversely, a "loss" of the translocation in 11 patients. Two
      hypotheses were raised: either an acquisition of the translocation during
      evolution or the existence of small t(4;14)-positive subclones at the time of
      diagnosis. To address this question, we had the opportunity to analyze two
      patients at the time of diagnosis by RT-PCR (reverse transcription-polymerase
      chain reaction) to look for the chimeric EMU-MMSET transcript, and one patient
      positive at diagnosis, but negative at relapse. The samples were positive,
      supporting the second hypothesis. Furthermore, the IGH sequences of two patients
      who "lose" the t(4;14) were identical at diagnosis and relapse, confirming the
      existence of a common ancestral clone. CONCLUSION: Thus, the conclusion of this
      study is that the t(4;14) is not a primary event in multiple myeloma and that it
      can be present in silent subclones at diagnosis, but also at relapse.

PMID- 23857604
TI  - Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and
      EGFRvIII for brain tumor therapy.
AB  - PURPOSE: The EGF receptor gene (EGFR) is most frequently amplified and
      overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We
      tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)
      PE38KDEL, which is reactive with a 55-amino acid (AA) region present in the
      extracellular domain of both EGFRwt (583-637 AAs) and EGFRvIII (292-346 AAs)
      proteins. EXPERIMENTAL DESIGN: The binding affinity and specificity of D2C7
      (scdsFv)-PE38KDEL for EGFRwt and EGFRvIII were measured by surface-plasmon
      resonance and flow cytometry. In vitro cytotoxicity of D2C7-(scdsFv)-PE38KDEL was
      measured by inhibition of protein synthesis in human EGFRwt-transfected NR6
      (NR6W), human EGFRvIII-transfected NR6 (NR6M), EGFRwt-overexpressing A431
      epidermoid-carcinoma, and glioblastoma xenograft cells (43, D08-0493MG, D2159MG,
      and D270MG). In vivo antitumor efficacy of D2C7-(scdsFv)-PE38KDEL was evaluated
      using 43, NR6M, and D270MG orthotopic tumor models. RESULTS: The KD of D2C7
      (scdsFv)-PE38KDEL for EGFRwt and EGFRvIII was 1.6*10(-9) mol/L and 1.3*10(-9)
      mol/L, respectively. Flow cytometry with NR6W and NR6M cells confirmed the
      specificity of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII. The D2C7-(scdsFv)
      PE38KDEL IC50 was 0.18 to 2.5 ng/mL on cells expressing EGFRwt (NR6W, A431, 43,
      and D08-0493MG). The D2C7-(scdsFv)-PE38KDEL IC50 was approximately 0.25 ng/mL on
      EGFRvIII-expressing cells (NR6M) and on EGFRwt- and EGFRvIII-expressing
      glioblastoma xenograft cells (D2159MG and D270MG). Significantly, in intracranial
      tumor models of 43, NR6M, and D270MG, treatment with D2C7-(scdsFv)-PE38KDEL by
      convection-enhanced delivery prolonged survival by 310% (P=0.006), 28% (P=0.002),
      and 166% (P=0.001), respectively. CONCLUSIONS: In preclinical studies, the D2C7
      (scdsFv)-PE38KDEL immunotoxin exhibited significant potential for treating brain
      tumors expressing EGFRwt, EGFRvIII, or both.

PMID- 23857605
TI  - Lamin B1 is a novel therapeutic target of betulinic acid in pancreatic cancer.
AB  - PURPOSE: Betulinic acid, a naturally occurring pentacyclic triterpenoid, exhibits
      potent antitumor activities, whereas the underlying mechanisms remain unclear. In
      the current study, we sought to determine the role and regulation of lamin B1
      expression in human pancreatic cancer pathogenesis and betulinic acid-based
      therapy. EXPERIMENTAL DESIGN: We used cDNA microarray to identify betulinic acid
      target genes and used tissue microarray to determine the expression levels of
      lamin B1 in pancreatic cancer tissues and to define their relationship with the
      clinicopathologic characteristics of pancreatic cancer. We also used in vitro and
      in vivo models to determine the biologic impacts of altered lamin B1 expression
      on and mechanisms underlying lamin B1 overexpression in human pancreatic cancer.
      RESULTS: We found that lamin B1 was significantly downregulated by betulinic acid
      treatment in pancreatic cancer in both in vitro culture and xenograft models.
      Overexpression of lamin B1 was pronounced in human pancreatic cancer, and
      increased lamin B1 expression was directly associated with low-grade
      differentiation, increased incidence of distant metastasis, and poor prognosis of
      patients with pancreatic cancer. Furthermore, knockdown of lamin B1 significantly
      attenuated the proliferation, invasion, and tumorigenicity of pancreatic cancer
      cells. CONCLUSIONS: Lamin B1 plays an important role in pancreatic cancer
      pathogenesis and is a novel therapeutic target of betulinic acid treatment.

PMID- 23857606
TI  - Capillary gel electrophoresis for the quantification and purity determination of
      recombinant proteins in inclusion bodies.
AB  - In this work, a high-resolution CGE method for quantification and purity
      determination of recombinant proteins was developed, involving a single-component
      inclusion bodies (IBs) solubilization solution. Different recombinant proteins
      expressed as IBs were used to show method capabilities, using recombinant
      interferon-beta 1b as the model protein for method validation. Method linearity
      was verified in the range from 0.05 to 0.40 mg/mL and a determination coefficient
      (r(2) ) of 0.99 was obtained. The LOQs and LODs were 0.018 and 0.006 mg/mL,
      respectively. RSD for protein content repeatability test was 2.29%. In addition,
      RSD for protein purity repeatability test was 4.24%. Method accuracy was higher
      than 90%. Specificity was confirmed, as the method was able to separate
      recombinant interferon-beta 1b monomer from other aggregates and impurities.
      Sample content and purity was demonstrated to be stable for up to 48 h. Overall,
      this method is suitable for the analysis of recombinant proteins in IBs according
      to the attributes established on the International Conference for Harmonization
      guidelines. 

PMID- 23857607
TI  - A hundred-year of Karl Jaspers' General Psychopathology (Allgemeine
      Psychopathologie)--1913-2013: a pivotal book in the history of psychiatry.
AB  - After a hundred-years of its publication, the Karl Jaspers' book, General
      Psychopathology, is still an indispensable book to psychiatrists and for all
      those who study psychopathology. It's a clear delineation of the phenomenological
      method for describing the symptoms of mental disorders that remains unmatched
      until nowadays. The book focuses on the relevance of phenomenological and
      hermeneutical methods in psychopathology. Although this work is grounded in the
      clinical thought and practices of the late nineteenth and early twentieth
      centuries, Jaspers' delineation of psychiatric methods in this work is still
      evaluated as unmatched to this day, a work that is indispensable to contemporary
      psychiatry. Jaspers also contributed with important articles and book reviews to
      psychiatric periodicals during the first two decades of the twentieth century. 

PMID- 23857608
TI  - Brachial plexus cyst in a patient with multifocal motor neuropathy.

PMID- 23857610
TI  - Exposure to pesticides and heterozygote genotype of GSTP1-Alw26I are associated
      to Parkinson's disease.
AB  - OBJECTIVE: This study aimed to analyze the frequency of GSTP1-Alw26I polymorphism
      and to estimate its association with toxic substances in Parkinson's disease
      (PD). METHODS: A study group with 154 patients - subdivided into familial and
      sporadic PD groups - and 158 elderly individuals without the disease (control
      group) were evaluated. GSTP1-Alw26I polymorphism was analyzed by polymerase chain
      reaction/restriction fragment length polymorphism (PCR-RFLP). RESULTS: Patients
      were significantly more exposed to pesticides compared with the control group
      (p=0.0004), and the heterozygote genotype associated to exposure to pesticides
      also prevailed in patients (p=0.0001). Wild homozygote genotype was related to
      tobacco use (p=0.043) and alcoholism (p=0.033) in familial PD patients.
      CONCLUSION: Exposure to pesticides is associated to PD, whose effect can be
      enhanced when combined with the heterozygote genotype of GSTP1-Alw26I. Also,
      large genetic and environmental studies considering tobacco use, alcoholism,
      GSTP1 and PD are necessary to confirm our findings.

PMID- 23857612
TI  - Distal acquaried demylinating symmetric neuropathy in two patients with essential
      hiperIgEmia.

PMID- 23857611
TI  - Visual pathway abnormalities were found in most multiple sclerosis patients
      despite history of previous optic neuritis.
AB  - OBJECTIVE: It was to investigate visual field (VF) abnormalities in a group of
      multiple sclerosis (MS) patients in the remission phase and the presence of
      magnetic resonance imaging (MRI) lesions in the optic radiations. METHODS: VF was
      assessed in 60 participants (age range 20-51 years): 35 relapsing-remitting MS
      patients [20 optic neuritis (+), 15 optic neuritis (-)] and 25 controls. MRI (3
      Tesla) was obtained in all patients. RESULTS: Visual parameters were abnormal in
      MS patients as compared to controls. The majority of VF defects were diffuse. All
      patients except one had posterior visual pathways lesions. No significant
      difference in lesion number, length and distribution was noted between patients
      with and without history of optic neuritis. One patient presented homonymous
      hemianopsia. CONCLUSION: Posterior visual pathway abnormalities were found in
      most MS patients despite history of previous optic neuritis.

PMID- 23857613
TI  - Myasthenia gravis and thymus: long-term follow-up screening of thymectomized and
      non-thymectomized patients.
AB  - Thymoma screening is recommended at the onset of myasthenia gravis (MG) or when
      patients with MG present with clinical deterioration or a progressive increase of
      anti-acetylcholine receptor antibody. However, it is unknown if it is necessary
      to repeat the screening of thymoma at fixed intervals, even in the absence of MG
      deterioration, when the initial screening is negative. We analyzed the recurrence
      rate and incidence of new thymoma in a series of patients with well-controlled
      MG. The sample consisted of 53 patients, aged 17 to 72 years, and the follow-up
      varied between 75 and 472 months. The chest computerized tomography detected
      thymus abnormalities in eight patients at the initial screening and no
      abnormalities in all patients at a second screening after five years. The
      findings of this study support the classical opinion that screening for thymoma
      should be recommended only if there is clinical deterioration due to the disease.

PMID- 23857614
TI  - Latin American consensus on guidelines for chronic migraine treatment.
AB  - Chronic migraine is a condition with significant prevalence all around the world
      and high socioeconomic impact, and its handling has been challenging
      neurologists. Developments for understanding its mechanisms and associated
      conditions, as well as that of new therapies, have been quick and important, a
      fact which has motivated the Latin American and Brazilian Headache Societies to
      prepare the present consensus. The treatment of chronic migraine should always be
      preceded by a careful diagnosis review; the detection of possible worsening
      factors and associated conditions; the stratification of
      seriousness/impossibility to treat; and monitoring establishment, with a pain
      diary. The present consensus deals with pharmacological and nonpharmacological
      forms of treatment to be used in chronic migraine. 

PMID- 23857615
TI  - Effects of early spasticity treatment on children with hemiplegic cerebral palsy:
      a preliminary study.
AB  - OBJECTIVE: To compare motor and functional performance of two groups of children
      with hemiplegic cerebral palsy (HCP). Only the study group (SG) received early
      treatment of spasticity with botulinum neurotoxin type A (BXT-A). METHODS: Gross
      Motor Function Measure (GMFM), functional performance (Pediatric Evaluation of
      Disability Inventory - PEDI), range of movement, gait pattern (Physician Rating
      Scale - PRS) and the speed of hand movements were considered. RESULTS: The SG,
      composed of 11 HCP (45.64+/-6.3 months), was assessed in relation to the
      comparison group, composed of 13 HCP (45.92+/-6.4 months). SG showed higher
      scores in four of the five GMFM dimensions, which included scores that were
      statistically significant for dimension B, and higher scores in five of the six
      areas evaluated in the PEDI. Active wrist extension, the speed of hand movements
      and PRS score were higher in the SG. CONCLUSION: Children who received early BXT
      A treatment for spasticity showed higher scores in motor and functional
      performance.

PMID- 23857616
TI  - Omega-3 intake in people with epilepsy under regular hemodialysis program: here
      to stay.
AB  - Among the many risk factors suggested for sudden unexpected death in epilepsy
      (SUDEP), higher frequency of seizures is a very consistent issue. Furthermore, it
      has been established that hemodialysis-associated seizure is a complication of
      the dialysis procedure. Thus, since a possible relation between cardiovascular
      abnormalities and SUDEP among patients with chronic renal insufficiency in
      regular hemodialysis program should not be neglected, we propose in this paper
      that omega-3 fatty acids offer opportunities for prevention of sudden cardiac
      death or improved treatment in people with epilepsy under the regular
      hemodialysis program. 

PMID- 23857617
TI  - Shock, diaschisis and von Monakow.
AB  - The concept of shock apparently emerged in the middle of the 18th century
      (Whyett) as an occurrence observed experimentally after spinal cord transection,
      and identified as "shock" phenomenon one century later (Hall). The concept was
      extended (Brown-Sequard) and it was suggested that brain lesions caused
      functional rupture in regions distant from the injured one ("action a distance").
      The term "diaschisis" (von Monakow), proposed as a new modality of shock, had its
      concept broadened, underpinned by observations of patients, aiming at
      distinguishing between symptoms of focal brain lesions and transitory effects
      they produced, attributable to depression of distant parts of the brain connected
      to the injured area. Presently, diaschisis is related mainly to cerebrovascular
      lesions and classified according to the connection fibers involved, as proposed
      by von Monakow. Depression of metabolism and blood flow in regions anatomically
      separated, but related by connections with the lesion, allows observing
      diaschisis with neuroimaging. 

PMID- 23857618
TI  - Chronic unremitting headache associated with Lyme disease-like illness.
AB  - The Brazilian Lyme-disease-like illness (BLDLI) or Baggio-Yoshinari syndrome is a
      unique zoonosis found in Brazil. It reproduces all the clinical symptoms of Lyme
      disease except for the high frequencies of relapse and the presence of autoimmune
      manifestations. Two cases of borreliosis manifesting with unremitting headache,
      which is a symptom associated with late-stage BLDLI, were presented. Clinical,
      therapeutic, and prognostic aspects of the BLDLI and its associated headaches
      were showed and discussed in this article. BLDLI diagnosis requires additional
      attention by physicians, since the disease has a tendency to progress to the
      late, recurrent stage or the chronic form, and the associated headache can be
      confused with chronic primary headache or with analgesic-overuse one. Special
      attention should be paid to patients with headaches who have traveled to endemic
      areas. 

PMID- 23857619
TI  - Codon 129 polymorphism of prion protein gene in is not a risk factor for
      Alzheimer's disease.
AB  - Interaction of prion protein and amyloid-b oligomers has been demonstrated
      recently. Homozygosity at prion protein gene (PRNP) codon 129 is associated with
      higher risk for Creutzfeldt-Jakob disease. This polymorphism has been addressed
      as a possible risk factor in Alzheimer disease (AD). OBJECTIVE: To describe the
      association between codon 129 polymorphisms and AD. METHODS: We investigated the
      association of codon 129 polymorphism of PRNP in 99 AD patients and 111 controls,
      and the association between this polymorphism and cognitive performance. Other
      polymorphisms of PRNP and additive effect of apolipoprotein E gene (ApoE) were
      evaluated. RESULTS: Codon 129 genotype distribution in AD 45.5% methionine (MM),
      42.2% methionine valine (MV), 12.1% valine (VV); and 39.6% MM, 50.5% MV, 9.9% VV
      among controls (p>0.05). There were no differences of cognitive performance
      concerning codon 129. Stratification according to ApoE genotype did not reveal
      difference between groups. CONCLUSION: Codon 129 polymorphism is not a risk
      factor for AD in Brazilian patients.

PMID- 23857620
TI  - Prion protein gene in Alzheimer's disease.

PMID- 23857621
TI  - Diagnosis at a first glance? "Bulging eyes" as a clue for a more accurate
      diagnosis in spinocerebellar ataxias.

PMID- 23857622
TI  - Circadian variation of fatigue in both patients with paralytic poliomyelitis and
      post-polio syndrome.
AB  - OBJECTIVE: It was to evaluate the degree of fatigue in patients with paralytic
      poliomyelitis (PP) and with post-polio syndrome (PPS), and correlate it with
      parameters of sleep and the circadian cycle. METHODS: Thirty patients, 17 female
      (56.7%), participated in the study: they answered the Revised Piper Fatigue Scale
      and performed a nocturnal polysomnographic study. Eleven had PP (mean age+/
      standard deviation of 47.9+/-6.4 years), and 19 had PPS (mean age+/-standard
      deviation of 46.4+/-5.6 years). RESULTS: Our study showed that fatigue was worse
      in the afternoon in the PP Group and had a progressive increase throughout the
      day in the PPS Group. We also observed compromised quality of sleep in both
      groups, but no statically significant difference was found in the sleep
      parameters measured by polysomnography. CONCLUSION: Fatigue has a well-defined
      circadian variation, especially in PPS Group. Poor sleep quality is associated
      with fatigue and, therefore, sleep disturbances should be evaluated and treated
      in this group of PPS.

PMID- 23857623
TI  - Ulnar sensory-motor amplitude ratio: a new tool to differentiate ganglionopathy
      from polyneuropathy.
AB  - The objective of this study was to evaluate if the ratio of ulnar sensory nerve
      action potential (SNAP) over compound muscle action potential (CMAP) amplitudes
      (USMAR) would help in the distinction between ganglionopathy (GNP) and
      polyneuropathy (PNP). METHODS: We reviewed the nerve conductions studies and
      electromyography (EMG) of 18 GNP patients, 33 diabetic PNP patients and 56
      controls. GNP was defined by simultaneous nerve conduction studies (NCS) and
      magnetic resonance imaging (MRI) abnormalities. PNP was defined by usual clinical
      and NCS criteria. We used ANOVA with post-hoc Tukey test and ROC curve analysis
      to compare ulnar SNAP and CMAP, as well as USMAR in the groups. RESULTS: Ulnar
      CMAP amplitudes were similar between GNP x PNP x Controls (p=0.253), but ulnar
      SNAP amplitudes (1.6+/-3.2 x 11.9+/-9.1 * 45.7+/-24.7) and USMAR values (0.3+/
      0.3 * 1.5+/-0.9 * 4.6+/-2.2) were significantly different. A USMAR threshold of
      0.71 was able to differentiate GNP and PNP (94.4% sensitivity and 90.9%
      specificity). CONCLUSIONS: USMAR is a practical and reliable tool for the
      differentiation between GNP and PNP.

PMID- 23857624
TI  - Unilateral abdominal bulging caused by L1-L2 herniation.

PMID- 23857626
TI  - Clinical relevance of "bulging eyes" for the differential diagnosis of
      spinocerebellar ataxias.
AB  - OBJECTIVE: To investigate the relevance of the clinical finding of bulging eyes
      (BE) in a large Brazilian cohort of spinocerebellar ataxias (SCA), to assess its
      importance in clinical differential diagnosis among SCA. METHODS: Three hundred
      sixty-nine patients from 168 Brazilian families with SCA were assessed with
      neurological examination and molecular genetic testing. BE was characterized by
      the presence of eyelid retraction. Genetically ascertained SCA3 was detected in
      167 patients, SCA10 in 68 patients, SCA2 in 20, SCA1 in 9, SCA7 in 6, and SCA6 in
      3 patients. RESULTS: BE was detected in 123 patients with SCA (33.3%), namely 109
      of the 167 SCA3 patients (65.3%) and in 5 of the others SCA patients (1 SCA10
      patient, 2 SCA1 patients and 2 SCA2 patients). CONCLUSION: BE was detected in the
      majority of patients with SCA3 (65.3%) and could be used with a clinical tool for
      the differential diagnosis of SCA.

PMID- 23857627
TI  - White matter hyperintensities, executive function and global cognitive
      performance in vascular mild cognitive impairment.
AB  - Vascular mild cognitive impairment (VaMCI) represents an early symptomatic stage
      of vascular cognitive impairment and might be associated to fronto-executive
      dysfunction. METHODS: Twenty-six individuals (age: 73.11+/-7.90 years; 65.4%
      female; schooling: 9.84+/-3.61 years) were selected through neuropsychological
      assessment and neuroimaging. Clinical and neuroimaging data of VaMCI individuals
      (n=15) were compared to normal controls (NC, n=11) and correlated with Fazekas
      scale. RESULTS: VaMCI performed significantly worse than NC in Trail-Making Test
      (TMT) B, errors in TMT B, difference TMT B-A and Cambridge Cognitive Examination
      (CAMCOG) final scores. Correlations were found among scores in modified Fazekas
      scale and performances in TMT B (time to complete and errors), difference TMT B-A
      and CAMCOG total score. CONCLUSION: Extension of white matter hyperintensities
      might be correlated to poorer global cognition and impairments in a set of fronto
      executive functions, such as cognitive speed, set shifting and inhibitory control
      in VaMCI.

PMID- 23857629
TI  - Freiburg neuropathology case conference: a contrast-enhancing orbital, intra
      conal lesion.

PMID- 23857628
TI  - Impact of once-daily versus twice-daily dosing frequency on adherence to chronic
      medications among patients with venous thromboembolism.
AB  - BACKGROUND: Multiple daily dosing may be negatively associated with patient
      medication adherence; however, adherence-related data are lacking in a patient
      population with venous thromboembolism (VTE). OBJECTIVE: To assess the adherence
      rates between once-daily (OD) and twice-daily (BID) dosing regimens of chronic
      medications in patients with VTE. METHODS: We analyzed the PharMetrics Integrated
      Claims database (claims of commercial insurers in the US) from 1 January 2004,
      through 31 December 2009. Adult patients with continuous insurance coverage,
      newly initiated on diabetes mellitus or hypertension medication, and having at
      least one VTE diagnosis were included. Adherence to OD and BID therapies was
      calculated by using two measures: medication possession ratio (MPR) and
      proportion of days covered (PDC). Adherence was defined as an MPR or PDC >=0.8.
      Multivariate logistic regressions were conducted to compare the probability of
      adherence between the OD and BID groups adjusting for baseline confounders.
      RESULTS: A total of 4,867 OD and 1,069 BID patients were identified. Mean
      duration of exposure to therapy for OD and BID patients was 386 and 356 days (p =
      0.011), respectively. Based on MPR, 69 % of OD and 62 % of BID patients were
      adherent (p < 0.001). For PDC at 12 months, the proportion of adherent patients
      for the OD and BID groups was 45 and 36 % (p < 0.001), respectively. Adjusted
      odds ratios (95 % CI) of adherence for the OD relative to BID group were 1.61
      (1.37-1.89) based on MPR (p < 0.001) and 1.46 (1.16-1.83) based on PDC at 12
      months (p = 0.001). CONCLUSIONS: This study demonstrates that VTE patients
      treated with chronic medications on OD dosing regimens were associated with an
      approximately 39-61 % higher likelihood of adherence compared with subjects on
      BID dosing regimens.

PMID- 23857630
TI  - Methane emissions from river buffaloes fed on green fodders in relation to the
      nutrient [corrected] intake and digestibility.
AB  - Fifteen male Murrah buffalo calves (15-18 months, 227.98 +/- 4.44 kg body weight)
      were distributed randomly in to three equal groups and fed solely on either
      berseem (G1), oats (G2), or chicory fodder (G3). A digestibility trial followed
      by methane measurement using SF6 tracer technique was conducted. No significant
      difference was observed in nutrient intake; however, crude protein (CP) intake
      was lower in G2 (0.35 kg) than G1 (0.7) and in G3 (0.71) and non-fibrous
      carbohydrates (NFC), and neutral detergent insoluble CP (NDICP) intake was
      significantly (p < 0.05) higher in G3 (1.54 and 0.31 kg) followed by G2 (1.27 and
      0.2 kg) and G1 (1.06 and 0.18 kg). The digestible dry matter, organic matter,
      neutral detergent fiber, and ether extract intake was similar in all the groups,
      whereas the digestible CP and NFC intake was lower in G2 compared to G1 and G3.
      Chicory- and berseem-fed groups emitted 12.2 and 5.2 % less methane than oats-fed
      group. However, no significant difference was observed in the absolute methane
      loss and methane loss as percentage of energy intake (p > 0.05) among the groups.
      There was positive correlation between nutrient intake and total methane
      production. However, an inverse relationship was observed between total
      digestible carbohydrate intake and methane production (g/kg dry matter intake).
      The following regression equations were developed to estimate methane production:
      methane (g/kg BW) = 128.8553 + (167.7456 * dNDFI) + (216.32 * dCPI) - (40.3313 *
      dNFCI) and methane (g/d) = -1.7494 + (41.42 * NDFI) + (39.8686 * CPI) + (0.5197 *
      NFCI). 

PMID- 23857632
TI  - Hogan's modification of the Sanvenero-Rosselli velopharyngoplasty.
AB  - PURPOSE: A competent velopharyngeal mechanism is essential for the production of
      intelligible speech and the secondary procedure of the posterior pharyngeal flap
      may be necessary in some patients to achieve this goal. The purpose of this study
      was to examine short and long-term results between the Sanvenero-Rosselli and
      Hogan's modification of the cranially based velopharyngoplasty. METHODS: During a
      20-year period, 17 patients underwent secondarily a posterior pharyngeal flap to
      treat velopharyngeal incompetence. All the patients were treated in the same
      institution and under the supervision of the same stuff surgeon. Nine patients
      were operated on according to the Sanvenero-Rosselli method and eight according
      to Hogan's modification, which consists of the preparation of two mucosal flaps
      on the dorsal side of the soft palate. Both mucosal flaps are sutured at the base
      of the pharyngeal flap and cover its raw surface. RESULTS: Comparing the post
      operative condition of the patients in two groups to their pre-operative state,
      it was observed that speech and comprehensibility were significantly improved,
      but Hogan's technique produced better speech results. CONCLUSIONS: According to
      our limited experience, additional surgical effort to create mucosal flaps on the
      nasal surface of the soft palate in Hogan's technique is compensated for by the
      reliable and substantial advantages that this technique holds, compared to
      Sanvenero-Rosselli's original proposition.

PMID- 23857631
TI  - Susceptibility weighted imaging of cartilage canals in porcine epiphyseal growth
      cartilage ex vivo and in vivo.
AB  - PURPOSE: High-resolution visualization of cartilage canals has been restricted to
      histological methods and contrast-enhanced imaging. In this study, the
      feasibility of non-contrast-enhanced susceptibility weighted imaging (SWI) for
      visualization of the cartilage canals was investigated ex vivo at 9.4 T, further
      explored at 7 and 3 T and demonstrated in vivo at 7 T, using a porcine animal
      model. METHODS: SWI scans of specimens of distal femur and humerus from 1 to 8
      week-old piglets were conducted at 9.4 T using 3D-GRE sequence and SWI post
      processing. The stifle joints of a 2-week old piglet were scanned ex vivo at 7
      and 3 T. Finally, the same sites of a 3-week-old piglet were scanned, in vivo, at
      7 T under general anesthesia using the vendor-provided sequences. RESULTS: High
      contrast visualization of the cartilage canals was obtained ex vivo, especially
      at higher field strengths; the results were confirmed histologically. In vivo
      feasibility was demonstrated at 7 T and comparison of ex vivo scans at 3 and 7 T
      indicated feasibility of using SWI at 3 T. CONCLUSIONS: High-resolution 3D
      visualization of cartilage canals was demonstrated using SWI. This demonstration
      of fully noninvasive visualization opens new avenues to explore skeletal
      maturation and the role of vascular supply for diseases such as osteochondrosis.

PMID- 23857633
TI  - Stress among parents of children with attention deficit hyperactivity disorder, a
      Malaysian experience.
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a chronic
      debilitating illness with onset in early childhood. The objective of this study
      was to look at the impact of children with ADHD on their parents. METHODS: All
      parents with children diagnosed as having ADHD attending the Psychiatry
      Adolescent and Child Unit, University Malaya were included in this study. Their
      parenting stress was assessed using the Parent Stress Index. RESULTS: A total of
      95 parents participated in the study. The proportion of parents who reported
      significant stress in this study was much higher than in most studies (n = 69,
      73%). Significant correlation was found between the severity of the child's
      disorder (Children's Global Assessment Scale [CGAS] score) and the parents'
      stress level (OR 0.16, 95% CI 0.05-0.51). Mothers were significantly more
      stressed than fathers (OR 0.16, 95% CI 0.05-0.51) and non-Malay parents more
      stressed than the Malay parents (OR 3.92, 95% CI 1.29-11.94). Parents with
      children older than 12 years of age were six times more stressed than parents
      with children younger than 12 years old (OR 6.47, 95% CI 1.55-27.01). Stressed
      parents acknowledged that having a child with ADHD was their biggest worry.
      DISCUSSION: Stress has marked consequences on any person and has important
      bearings on their mental health. Stress among parents needs be looked into when
      treating children with ADHD.

PMID- 23857634
TI  - Multi-level micro/nanotexturing by three-dimensionally controlled
      photofluidization and its use in plasmonic applications.
AB  - The Field-Gradient Effect extends the photofluidization of azobenzene materials
      to 3D, multi-level micro/nanotexturing with a newly conceptualized design
      strategy based on "field-gradient photofluidization". In particular, we
      successfully characterized the vertical gradient optical absorption within the
      azobenzene material and the resulting field-gradient photofluidization both
      theoretically and experimentally. Furthermore, we could create the
      heterogeneously integrated micro/nanotextures at any desired surface heights,
      capability that is potentially beneficial for plasmonic applications. 

PMID- 23857635
TI  - Prospective memory deficits in euthymic bipolar disorder patients: a preliminary
      study.
AB  - INTRODUCTION: Prospective memory refers to the ability to remember to do
      something in the future. To date, little is known about prospective memory
      deficits in bipolar disorder (BD) in remission (euthymia). This study examined
      the nature and correlates of prospective memory in these patients. METHODS: Forty
      seven euthymic BD patients and 47 matched healthy controls formed the study
      sample. Socio-demographic and basic clinical characteristics, prospective memory
      (Cambridge Prospective Memory Test [CAMPROMPT]), retrospective memory (immediate
      Logical Memory subtests of the Wechsler Memory Scales-Revised [WMS-R]), IQ
      (Raven's Progressive Matrices) and executive functioning (Wisconsin Card Sorting
      Test) were measured in all participants; patients' symptoms were rated with the
      17-item Hamilton Depression Rating Scale and the 11-item Young Mania Rating
      Scale. RESULTS: Patients performed significantly worse on time-based prospective
      memory compared to controls. Multivariate analyses revealed that patients' lower
      score on Raven's Progressive Matrices significantly contributed to poor
      performance on time-based prospective memory, whereas lower scores on WMS-R
      Logical Memory subtest contributed to poor performance on event-based prospective
      memory; in controls, lower education level and older age significantly
      contributed to poor performance on time-based and event-based prospective memory,
      respectively. DISCUSSION: Prospective memory deficits persist in remitted BD
      patients suggesting that prospective memory impairment constitutes a trait
      deficit in BD.

PMID- 23857636
TI  - Three-dimensional structure of the toxin-delivery particle antifeeding prophage
      of Serratia entomophila.
AB  - The Serratia entomophila antifeeding prophage (Afp) is a bullet-shaped toxin
      delivery apparatus similar to the R-pyocins of Pseudomonas aeruginosa.
      Morphologically it resembles the sheathed tail of bacteriophages such as T4,
      including a baseplate at one end. It also shares features with the type VI
      secretion systems. Cryo-electron micrographs of tilted Afp specimens (up to 60
      degrees) were analyzed to determine the correct cyclic symmetry to overcome the
      limitation imposed by exclusively side views in nominally untilted specimens. An
      asymmetric reconstruction shows clear 6-fold cyclic symmetry contrary to a
      previous conclusion of 4-fold symmetry based on analysis of only the preferred
      side views (Sen, A., Rybakova, D., Hurst, M. R., and Mitra, A. K. (2010) J.
      Bacteriol. 192, 4522-4525). Electron tomography of negatively stained Afp
      revealed right-handed helical striations in many of the particles, establishing
      the correct hand. Higher quality micrographs of untilted specimens were processed
      to produce a reconstruction at 2.0-nm resolution with imposed 6-fold symmetry.
      The helical parameters of the sheath were determined to be 8.14 nm for the
      subunit rise along and 40.5 degrees  for the rotation angle around the helix. The
      sheath is similar to that of the T4 phage tail but with a different arrangement
      of the subdomain of the polymerizing sheath protein(s). The central tube is
      similar to the diameter and axial width of the Hcp1 hexamer of P. aeruginosa type
      VI secretion system. The tube extends through the baseplate into a needle
      resembling the "puncture device" of the T4 tail. The tube contains density that
      may be the toxin and/or a length-determining protein. 

PMID- 23857637
TI  - Cardiac assessment in fetuses with right-sided congenital diaphragmatic hernia:
      case-control study.
AB  - OBJECTIVE: To evaluate cardiac anatomy and function in fetuses with right-sided
      congenital diaphragmatic hernia (RCDH), and to compare these values with those of
      normal controls. METHODS: Fetal echocardiography was performed in 17 consecutive
      cases with isolated RCDH and 17 gestational age-matched controls. Two-dimensional
      measurements included ventricular and outflow tract diameters. Doppler ultrasound
      was used to measure the flow pattern in the ductus venosus and over the pulmonary
      and aortic valves, right and left ventricular myocardial performance index and
      the E/A wave ratio over the atrioventricular valves. Stroke volume, cardiac
      output and shortening fraction were calculated. RESULTS: Median gestational age
      at evaluation was 27.4 (interquartile range, 24.4-28.9) weeks. RCDH cases had a
      significantly smaller right ventricle and pulmonary valve diameter. Furthermore,
      stroke volume and cardiac output from the right ventricle were lower than in
      controls. Myocardial contractility, however, appeared normal. CONCLUSIONS:
      Despite significantly reduced right ventricular dimensions and cardiac output,
      cardiac contractility was normal in a cohort of fetuses with RCDH.

PMID- 23857640
TI  - Anatomical and scanning electron microscopic characteristics of the tongue in the
      pampas deer (Cervidae: Ozotoceros bezoarticus, Linnaeus 1758).
AB  - This study represents the first definitive anatomical description of the tongue
      and lingual papillae of the pampas deer and compares the different information on
      the morphology of the other ruminant species available in the literature. In this
      study, the tongues of four adult and one fetal deer were used. The tongue was
      elongated with an oval or rounded apex. The filiform papillae on the lingual apex
      were smaller than the ones on the dorsal and lateral surfaces of the lingual
      body. Two very thin secondary papillary projections were found to emerge from the
      bilateral sides of some filiform papillae. Spherical fungiform papillae were
      randomly distributed among filiform papillae on dorsal surface of the lingual
      body and ventral surface of the apex. More developed conical papillae were
      observed in the caudal half of the lingual torus, whereas the rostral half of the
      torus had smaller conical papillae. Each conical papilla included shallow
      longitudinal groove on its anterior surface and some conical papillae on the
      lingual torus had bifid sharp apices. On the caudal portion of the torus, we also
      observed a few fungiform papillae, which were larger than those located on the
      lingual body. There were no lenticular papillae on the lingual torus, and five to
      nine round or oval circumvallate papillae were situated on each caudolateral side
      of the lingual torus. Morphological features of the tongue in the pampas deer
      were more similar to wild ruminant species than they were to domestic species.

PMID- 23857638
TI  - Micafungin for empirical antifungal therapy in patients with febrile neutropenia:
      multicenter phase 2 study.
AB  - Empirical antifungal therapy is the current standard of care for patients with
      febrile neutropenia unresponsive to broad-spectrum antimicrobials. Although a
      number of antifungal agents are currently available, the need remains for
      effective but less toxic alternatives for this indication. We therefore conducted
      a phase 2 study of micafungin for 80 patients with hematologic diseases who were
      suffering from persistent or recurrent fever after at least 96 h of antibacterial
      therapy. The patients were treated with micafungin at a fixed dose of 150 mg/day.
      Of the 78 evaluable patients, 54 (69 %) achieved defervescence by the time of
      neutrophil recovery, and 56 (72 %) completed the treatment in accordance with the
      provision of the protocol. Four patients developed invasive fungal infection,
      nine changed antifungal therapy because of lack of efficacy, and three
      discontinued micafungin because of drug-related adverse events. Based on the
      composite end point taking account of these, the overall treatment success rate
      was 60 %, with the lower limit of a 90 % confidence interval (50.3 %) exceeding
      the predefined threshold success rate (50 %). These findings show the efficacy
      and safety of micafungin for empirical antifungal therapy in patients with
      persistent or recurrent febrile neutropenia, warranting further investigation of
      this drug in a phase 3 study. 

PMID- 23857641
TI  - Increased enamel hypoplasia and very low birthweight infants.
AB  - Birth cohort studies of developmental defects of enamel (DDE) and early childhood
      caries (ECC) in very low birthweight (VLBW) and normal birthweight (NBW) infants
      are rare. In this birth cohort of 234 VLBW and 234 NBW infants, we report the
      incidence of ECC and DDE at 8 and 18-20 mos of corrected age. Infant medical and
      maternal socio-demographic data were abstracted from medical records at birth.
      Dental assessments for ECC and DDE (enamel hypoplasia, demarcated and diffuse
      opacities) were completed at 8 and 18-20 mos. The incidence of hypoplasia was
      significantly higher in VLBW compared with NBW infants (8 mos, 19% vs. 2%; 18
      mos, 31% vs. 8%). The incidence of ECC (International Caries Detection and
      Assessment System: ICDAS >= 2) was 1.4% (8 mos) and 12% (18-20 mos) and was
      similar between the VLBW and NBW groups. At both ages, using a beta-binomial
      regression model to control for potential confounders (maternal and infant
      characteristics), we found increased risk for enamel hypoplasia among the VLBW
      infants compared with the NBW infants. African Americans had a lower risk for
      enamel hypoplasia at 18-20 mos. The VLBW infants should be monitored for ECC due
      to the presence of enamel hypoplasia.

PMID- 23857642
TI  - Current perspectives: calcium phosphate nanocoatings and nanocomposite coatings
      in dentistry.
AB  - The purpose of coatings on implants is to achieve some or all of the improvements
      in biocompatibility, bioactivity, and increased protection from the release of
      harmful or unnecessary metal ions. During the last decade, there has been
      substantially increased interest in nanomaterials in biomedical science and
      dentistry. Nanocomposites can be described as a combination of two or more
      nanomaterials. By this approach, it is possible to manipulate mechanical
      properties, such as strength and modulus of the composites, to become closer to
      those of natural bone. This is feasible with the help of secondary substitution
      phases. Currently, the most common composite materials used for clinical
      applications are those selected from a handful of available and well
      characterized biocompatible ceramics and natural and synthetic polymers. This
      approach is currently being explored in the development of a new generation of
      nanocomposite coatings with a wider range of oral and dental applications to
      promote osseointegration. The aim of this review is to give a brief introduction
      into the new advances in calcium phosphate nanocoatings and their composites,
      with a range of materials such as bioglass, carbon nanotubes, silica, ceramic
      oxide, and other nanoparticles being investigated or used in dentistry. 

PMID- 23857643
TI  - Cluster Effects in a National Dental PBRN restorative study.
AB  - Items in clusters, such as patients of the same clinician or teeth within the
      same patient, tend to be more similar than items from different groups. This
      within-group similarity, represented by the intraclass correlation coefficient
      (ICC), reduces precision, yielding less statistical power and wider confidence
      intervals, compared with non-clustered samples of the same size. This must be
      considered in the design of studies including clusters. We present ICC estimates
      from a study of 7,826 restorations placed in previously unrestored tooth surfaces
      of 4,672 patients by 222 clinicians in the National Dental Practice-Based
      Research Network, as a resource for sample size planning in restorative studies.
      Our findings suggest that magnitudes of ICCs in practice-based research can be
      substantial. These can have large effects on precision and the power to detect
      treatment effects. Generally, we found relatively large ICCs for characteristics
      that are influenced by clinician choice (e.g., 0.36 for rubber dam use). ICCs for
      outcomes within individual patients, such as tooth surfaces affected by a caries
      lesion, tended to be smaller (from 0.03 to 0.15), but were still sufficiently
      large to substantially affect statistical power. Clustering should be taken into
      account in the design of oral health studies and derivation of statistical power
      estimates for these studies (ClinicalTrials.gov, NCT00847470).

PMID- 23857645
TI  - Neutral buoyancy is optimal to minimize the cost of transport in horizontally
      swimming seals.
AB  - Flying and terrestrial animals should spend energy to move while supporting their
      weight against gravity. On the other hand, supported by buoyancy, aquatic animals
      can minimize the energy cost for supporting their body weight and neutral
      buoyancy has been considered advantageous for aquatic animals. However, some
      studies suggested that aquatic animals might use non-neutral buoyancy for gliding
      and thereby save energy cost for locomotion. We manipulated the body density of
      seals using detachable weights and floats, and compared stroke efforts of
      horizontally swimming seals under natural conditions using animal-borne
      recorders. The results indicated that seals had smaller stroke efforts to swim a
      given speed when they were closer to neutral buoyancy. We conclude that neutral
      buoyancy is likely the best body density to minimize the cost of transport in
      horizontal swimming by seals. 

PMID- 23857644
TI  - Anticardiolipin in porphyromonas gingivalis antisera causes fetal loss in mice.
AB  - beta2-glycoprotein I (beta2GPI)-dependent anticardiolipin autoantibodies (aCl)
      are associated with thrombosis and fetal loss. Some microbial pathogens can
      induce pathogenic antibodies cross-reactive with beta2GPI. Sera from a
      significant percentage of periodontitis patients contain aCl, and some
      periodontal pathogens contain antigens with peptide sequences having homology to
      beta2GPI. We hypothesized that antibodies raised against P. gingivalis (aPg)
      contain pathogenic aCl that induce fetal resorption. We immunized mice with
      beta2GPI, P. gingivalis W83, or an arg-gingipain-defective mutant of P.
      gingivalis (HF18). IgG fractions of aPg were immunoabsorbed to remove aCl-like
      antibodies (abs-aPg). IgG fractions were administered intravenously into tail
      veins of mated BALB/c females at day 0 of pregnancy. At day 15, the proportions
      of fetal resorptions were evaluated. The prevalence of fetal loss was
      significantly greater in the aPg group than in the control IgG group (21.2% vs.
      5.3%, p = .001), and greater in the aPg group than in the abs-aPg group (21.2%
      vs. 12%, p < .05). There were no fetal resorptions observed in the aPgHF18 group
      (p = .0005 compared with aPg, p = .17 compared with control). aPg antibody
      contains activity consistent with pathogenic aCl, and the antigen inducing the
      antibodies that cause increased fetal loss may be on the arg-gingipain protease
      of P. gingivalis.

PMID- 23857646
TI  - Serial coupling of RP and zwitterionic hydrophilic interaction LC-MS: suspects
      screening of diclofenac transformation products by oxidation with a boron-doped
      diamond electrode.
AB  - The presence of pollutants and their transformation products (TPs) in the water
      system is a big concern because of possible adverse effects on the aquatic
      environment. Their identification is still a challenge that requires the
      combination of different chromatographic techniques. In the current research,
      serial coupling of RPLC and zwitterionic hydrophilic interaction LC with TOF-MS
      was investigated as a single separation technique for the screening of suspected
      TPs from electrochemical oxidation of diclofenac using a boron-doped diamond
      electrode. Diclofenac oxidation was performed in three water matrices in order to
      study its transformation in different chemical contexts. 47 TPs resulting from
      similar oxidation methods were selected from the literature. As in most cases
      standards were not available, an identification procedure based on accurate mass
      data and chromatographic behavior was proposed. According to this procedure, 11
      suspected TPs, previously analyzed by LC, GC, or ion chromatography, were
      detected in a single injection. The method was proved to be reliable and
      versatile and it could be efficiently employed as a comprehensive analytical tool
      for the simultaneous analysis of compounds in a wide polarity range. 

PMID- 23857647
TI  - Utilization of paramagnetic microparticles for automated isolation of free
      circulating mRNA as a new tool in prostate cancer diagnostics.
AB  - Determination of serum mRNA gained a lot of attention in recent years,
      particularly from the perspective of disease markers. Streptavidin-modified
      paramagnetic particles (SMPs) seem an interesting technique, mainly due to
      possible automated isolation and high efficiency. The aim of this study was to
      optimize serum isolation protocol to reduce the consumption of chemicals and
      sample volume. The following factors were optimized: amounts of (i) paramagnetic
      particles, (ii) oligo(dT)20 probe, (iii) serum, and (iv) the binding sequence
      (SMPs, oligo(dT)20 , serum vs. oligo(dT)20 , serum and SMPs). RNA content was
      measured, and the expression of metallothionein-2A as possible prostate cancer
      marker was analyzed to demonstrate measurable RNA content with ability for RT-PCR
      detection. Isolation is possible on serum volume range (10-200 MUL) without
      altering of efficiency or purity. Amount of SMPs can be reduced up to 5 MUL, with
      optimal results within 10-30 MUL SMPs. Volume of oligo(dT)20 does not affect
      efficiency, when used within 0.1-0.4 MUL. This optimized protocol was also
      modified to fit needs of automated one-step single-tube analysis with identical
      efficiency compared to conventional setup. One-step analysis protocol is
      considered a promising simplification, making RNA isolation suitable for
      automatable process. 

PMID- 23857648
TI  - Effect of thermal cycling on denture base and autopolymerizing reline resins.
AB  - OBJECTIVE: This study evaluated the fracture toughness (FT) of denture base and
      autopolymerizing reline resins, with and without thermocycling (T). MATERIAL AND
      METHODS: Specimens of each material (denture base acrylic resin - Lucitone 550 -
      L; autopolymerizing reline resins - Ufi Gel Hard-UH, Tokuyama Rebase II-TR, New
      Truliner-NT and Kooliner-K), were produced, notched and divided into two groups
      (n=10): CG (control group of autopolymerizing reline resins and L): FT tests were
      performed after polymerization; TG (thermocycled group): FT tests were performed
      after T (5 degrees C and 55 degrees C for 5,000 cycles). RESULTS: Results
      (MPa.m1/2) were analyzed by two-way ANOVA and Tukey's test (p=0.05). L exhibited
      the highest FT mean values in both groups (CG - 2.33; TG - 2.17). For the CG
      groups, NT showed the highest FT (1.64) among the autopolymerizing reline resins,
      and K the lowest (1.04). After T, when the autopolymerizing reline resins were
      compared, a statistically significant difference in FT was found only between the
      NT (1.46) and TR (1.00). CONCLUSIONS: Thermocycling increased the FT of K and did
      not influence the FT of L, UH, TR and NT.

PMID- 23857649
TI  - Effect of MTA-based sealer on the healing of periapical lesions.
AB  - Some manufacturers have recently added specific components to improve the ease of
      handling and insertion material properties of MTA in order to create MTA-based
      sealers. OBJECTIVE: The aim of this study was to evaluate the healing of
      periapical lesions in canine teeth after a single session of endodontic treatment
      with MTA Fillapex(r) compared with Sealapex(r) or Endo-CPM-Sealer(r). MATERIAL
      AND METHODS: Sixty-two root canals were performed on two 1-year-old male dogs.
      After coronal access and pulp extirpation, the canals were exposed to the oral
      cavity for 6 months in order to induce periapical lesions. The root canals were
      prepared, irrigated with a solution of 2.5% sodium hypochlorite and filled with
      gutta-percha and different sealers, according to the following groups: 1)
      Sealapex(r); 2) Endo-CPM-Sealer(r); and 3) MTA Fillapex(r). Some teeth with
      periapical lesions were left untreated for use as positive controls. Healthy
      teeth were used as negative controls. After 6 months, the animals were sacrificed
      and serial sections from the roots were prepared for histomorphologic analysis
      and stained with hematoxylin and eosin and the Brown and Brenn technique. The
      lesions were scored according to pre-established histomorphologic parameters and
      the scores statistically analyzed using the Kruskal-Wallis test. RESULTS: All 3
      materials produced similar patterns of healing (p>0.05); in particular,
      persistent inflammation and absence of complete periapical tissue healing were
      consistently noted. CONCLUSIONS: Preparation of the infected root canals followed
      by filling with the materials studied was insufficient to provide complete
      healing of the periapical tissues.

PMID- 23857650
TI  - Prediction of the mesiodistal size of unerupted canines and premolars for a group
      of Romanian children: a comparative study.
AB  - OBJECTIVES: The aim of the present study was to develop an optimization method of
      multiple linear regression equation (MLRE), using a genetic algorithm to
      determine a set of coefficients that minimize the prediction error for the sum of
      permanent premolars and canine dimensions in a group of young people from a
      central area of Romania represented by a city called Sibiu. MATERIAL AND METHODS:
      To test the proposed method, we used a multiple linear regression equation
      derived from the estimation method proposed by Mojers, to which we adjusted
      regression coefficients using the Breeder genetic algorithm. A total of 92
      children were selected with complete permanent teeth with no clinically visible
      dental caries, proximal restorations or orthodontic treatment. A hard dental
      stone was made for each of these models, which was then measured with a digital
      caliper. The Dahlberg analyses of variance had been performed to determine the
      error of method, then the Correlation t Test was applied, and finally the MLRE
      equations were obtained using the version 16 for Windows of the SPSS program.
      RESULTS: The correlation coefficient of MLRE was between 51-67% and the
      significance level was set at alpha=0.05. Comparing predictions provided by the
      new and respectively old method, we can conclude that the Breeder genetic
      algorithm is capable of providing the best values for parameters of multiple
      linear regression equations, and thus our equations are optimized for the best
      performance. CONCLUSION: The prediction error rates of the optimized equations
      using the Breeder genetic algorithm are smaller than those provided by the
      multiple linear regression equations proposed in the recent study.

PMID- 23857651
TI  - Long-term degradation of resin-based cements in substances present in the oral
      environment: influence of activation mode.
AB  - Indirect restorations in contact with free gingival margins or principally within
      the gingival sulcus, where the presence of organic acids produced by oral biofilm
      is higher, may present faster degradation of the resin-based cement pellicle.
      OBJECTIVES: To investigate the degradation of four resin-based cements: Rely X
      ARC (R), Variolink II (V), Enforce (E) and All Cem (A), after immersion in
      distilled water (DW), lactic acid (LA) and artificial saliva (AS) and to analyze
      the influence of the activation mode on this response. MATERIAL AND METHODS: Two
      activation modes were evaluated: chemical (Ch) and dual (D). In the dual
      activation, a two-millimeter thick ceramic disk (IPS Empress System) was
      interposed between the specimen and light-curing unit tip. Specimens were
      desiccated, immersed in distilled water, artificial saliva and lactic acid 0.1 M
      at 37 degrees C for 180 days, weighed daily for the first 7 days, and after 14,
      21, 28, 90 and 180 days and were desiccated again. Sorption and solubility (ug/mm
      3 ) were calculated based on ISO 4049. The data were submitted to multifactor
      analysis of variance (MANOVA) and Tukey's HSD test for media comparisons
      (alpha=0.05). RESULTS: Sorption was higher after immersion in LA (p<0.05) and
      increased significantly with time (p<0.05). Sorption was influenced by the
      activation mode: Ch>D (p<0.05). The lowest solubility was presented by R
      (p<0.05). CONCLUSIONS: Lactic acid increased the degradation of resin-based
      cements. Moreover, the physical component of activation, i.e., light-activation,
      contributed to a low degradation of resin-based cements.

PMID- 23857652
TI  - Opening and closure forces of sliding mechanisms of different self-ligating
      brackets.
AB  - Self-ligating brackets engage the wire by means of a slide mechanism. Forces that
      have to be applied to open and close the sliding mechanism of brackets are still
      unknown. OBJECTIVE: The aim of this study was to measure and compare the opening
      and closure forces of different self-ligating brackets. MATERIAL AND METHODS:
      Three different stainless steel self-ligating brackets (Carriere LX, Ortho
      Organizers; F1000, Leone; Damon Q, Ormco) were tested. For each different
      bracket, 20 maxillary right central incisors and 20 mandibular right central
      incisors were used. Opening and closure forces were measured using an Instron
      Universal Testing Machine. Statistical analysis was performed and ANOVA and Tukey
      tests were carried out. RESULTS: Opening forces were registered between 1.1 N and
      5.6 N, whereas closure forces were recorded between 1.57 N and 4.87 N.
      Significant differences were detected among the different brackets and between
      the two prescriptions tested. CONCLUSION: The knowledge of different opening and
      closure forces of self-ligating brackets can help the orthodontist in the
      clinical management of these devices.

PMID- 23857653
TI  - PAX9 polymorphism and susceptibility to sporadic non-syndromic severe anodontia:
      a case-control study in southwest China.
AB  - Our research aimed to look into the clinical traits and genetic mutations in
      sporadic non-syndromic anodontia and to gain insight into the role of mutations
      of PAX9, MSX1, AXIN2 and EDA in anodontia phenotypes, especially for the PAX9.
      MATERIAL AND METHODS: The female proband and her family members from the ethnic
      Han families underwent complete oral examinations and received a retrospective
      review. Venous blood samples were obtained to screen variants in the PAX9, MSX1,
      AXIN2, and EDA genes. A case-control study was performed on 50 subjects with
      sporadic tooth agenesis (cases) and 100 healthy controls, which genotyped a PAX9
      gene polymorphism (rs4904210). RESULTS: Intra-oral and panoramic radiographs
      revealed that the female proband had anodontia denoted by the complete absence of
      teeth in both the primary and secondary dentitions, while all her family members
      maintained normal dentitions. Detected in the female proband were variants of the
      PAX9 and AXIN2 including A240P (rs4904210) of the PAX9, c.148C>T (rs2240308),
      c.1365A>G (rs9915936) and c.1386C>T (rs1133683) of the AXIN2. The same variants
      were present in her unaffected younger brother. The PAX9 variations were in a
      different state in her parents. Mutations in the MSX1 and EDA genes were not
      identified. No significant differences were found in the allele and genotype
      frequencies of the PAX9 polymorphism between the controls and the subjects with
      sporadic tooth agenesis. CONCLUSIONS: These results suggest that the association
      of A240P with sporadic tooth agenesis still remains obscure, especially for
      different populations. The genotype/phenotype correlation in congenital anodontia
      should be verified.

PMID- 23857654
TI  - Effect of different disinfecting procedures on the hardness and color stability
      of two maxillofacial elastomers over time.
AB  - OBJECTIVE: Disinfection procedures often cause deterioration in a maxillofacial
      prosthesis. Color and hardness alterations could lead to a replacement of the
      prosthesis. MATERIAL AND METHODS: An experimental chlorinated polyethylene (CPE)
      and a commercial polydimethyl siloxane (PDMS) sample were treated with four
      different disinfection procedures for a period which simulates 1 year of clinical
      service. The applied disinfection procedures included microwave exposure and
      immersion in three solutions, sodium hypochlorite, neutral soap and a commercial
      disinfecting soap. Shore A hardness (?H) and color differences (?E) were
      determined before and after each procedure. All data were analyzed by Two Way
      Analysis of Variance (ANOVA) and Tukey's post hoc tests at a level of alpha=0.05.
      RESULTS: The samples presented significant alterations in color and hardness
      after the different disinfection treatments. The color differences (?E) were at
      least eye detectable in all cases and clinically unacceptable in most of the
      cases, with values ranging from 1.51 to 4.15 and from 1.54 to 5.92 for the PDMS
      and CPE material, respectively. Hardness was decreased after all the disinfection
      procedures in the PDMS, while for the CPE, a decrement was observed after
      disinfection with sodium hypochlorite and neutral soap and an increment after
      microwave exposure and the disinfection with a commercial antimicrobial agent.
      The PDMS samples presented greater alterations in color and hardness after
      disinfection with sodium hypochlorite solution, while the microwave exposure
      caused negligible effects. The CPE samples were affected most after disinfection
      when treated with neutral soap, and more slightly when disinfected with sodium
      hypochlorite solution. CONCLUSIONS: The disinfection procedures caused
      alterations in color and hardness of the examined materials. The most suitable
      disinfection procedure for the PDMS material is microwave exposure, while
      disinfection with sodium hypochlorite solution is not recommended. The CPE
      material is suggested to be disinfected with sodium hypochlorite solution and the
      use of neutral soap is not recommended. Comparing the two materials, the PDMS
      material is most color stable, while the CPE material presented fewer changes in
      hardness.

PMID- 23857655
TI  - Rehabilitative treatment of cleft lip and palate: experience of the Hospital for
      Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP) - Part 4: oral
      rehabilitation.
AB  - Treatment of patients with cleft lip and palate is completed with fixed
      prostheses, removable, total, implants and aims to restore aesthetics, phonetics
      and function and should be guided by the basic principles of oral rehabilitation,
      such as physiology, stability, aesthetics, hygiene and the expectations of the
      patient. In order to obtain longevity of a prosthetic rehabilitation, the
      periodontal and dental tissue as well as the biomechanics of the prosthesis are
      to be respected. The purpose of this article is to describe the types of
      prosthetics treatment, which are performed at HRAC/USP for the rehabilitation of
      cleft area in adult patients. 

PMID- 23857656
TI  - Oral granuloma gravidarum: a retrospective study of 41 cases in Southern Brazil.
AB  - Granuloma gravidarum (GG) is an inflammatory lesion, which develops in the oral
      mucosa of pregnant women in response to chronic low-grade irritants, under the
      influence of hormonal factors. Objective To characterize GG clinically by means
      of a retrospective study of the cases of the Oral Medicine Division, Sao Lucas
      Hospital, Brazil. Material and Methods Cases of GG diagnosed between 1980 and
      2012 were analyzed. Data were obtained referring to the age of the patients,
      lesion location, clinical features, as well as the presence of local irritants.
      The gestation period in which the lesion developed was also investigated. Results
      Forty-one cases of GG were found. The lesions developed predominantly in the
      third trimester of pregnancy (51.22%) and the mean age of the patients was 28
      years. Most GG was found in the gingiva (73.17%), was reddish color and had a
      mean diameter of 1.5 cm. Local irritants were involved in 75.6% of the cases.
      Conclusions The hormonal conditions of pregnancy can have an impact on the oral
      cavity, predisposing the patient to inflammatory lesions such as GG. 

PMID- 23857657
TI  - Mechanical performance of encapsulated restorative glass-ionomer cements for use
      with Atraumatic Restorative Treatment (ART).
AB  - The Atraumatic Restorative Treatment (ART) approach was suggested to be a
      suitable method to treat enamel and dentine carious lesions in patients with
      disabilities. The use of a restorative glass-ionomer with optimal mechanical
      properties is, therefore, very important. OBJECTIVE: To test the null-hypotheses
      that no difference in diametral tensile, compressive and flexural strengths
      exists between: (1) The EQUIA system and (2) The Chemfil Rock (encapsulated glass
      ionomers; test materials) and the Fuji 9 Gold Label and the Ketac Molar Easymix
      (hand-mixed conventional glass-ionomers; control materials); (3) The EQUIA system
      and Chemfil Rock. MATERIAL AND METHODS: Specimens for testing flexural (n = 240)
      and diametral tensile (n=80) strengths were prepared according to standardized
      specifications; the compressive strength (n=80) was measured using a tooth-model
      of a class II ART restoration. ANOVA and Tukey B tests were used to test for
      significant differences between dependent and independent variables. RESULTS: The
      EQUIA system and Chemfil Rock had significantly higher mean scores for all the
      three strength variables than the Fuji 9 Gold Label and Ketac Molar Easymix
      (alpha=0.05). The EQUIA system had significant higher mean scores for diametral
      tensile and flexural strengths than the Chemfil Rock (alpha=0.05). CONCLUSION:
      The two encapsulated high-viscosity glass-ionomers had significantly higher test
      values for diametral tensile, flexural and compressive strengths than the
      commonly used hand-mixed high-viscosity glass-ionomers.

PMID- 23857658
TI  - High-efficiency tooth bleaching using non-thermal atmospheric pressure plasma
      with low concentration of hydrogen peroxide.
AB  - Light-activated tooth bleaching with a high hydrogen peroxide (HP; H2O2)
      concentration has risks and the actual role of the light source is doubtful. The
      use of conventional light might result in an increase in the temperature and
      cause thermal damage to the health of the tooth tissue. OBJECTIVE: This study
      investigated the efficacy of tooth bleaching using non-thermal atmospheric
      pressure plasma (NAPP) with 15% carbamide peroxide (CP; CH6N2O3) including 5.4%
      HP, as compared with conventional light sources. MATERIAL AND METHODS: Forty
      human teeth were randomly divided into four groups: Group I (CP+NAPP), Group II
      (CP+plasma arc lamp; PAC), Group III (CP+diode laser), and Group IV (CP alone).
      Color changes (?E) of the tooth and tooth surface temperatures were measured.
      Data were evaluated by one-way analysis of variance (ANOVA) and post-hoc Tukey's
      tests. RESULTS: Group I showed the highest bleaching efficacy, with a ?E value of
      1.92-, 2.61 and 2.97-fold greater than those of Groups II, III and IV,
      respectively (P<0.05). The tooth surface temperature was maintained around 37
      degrees C in Group I, but it reached 43 degrees C in Groups II and III.
      CONCLUSIONS: The NAPP has a greater capability for effective tooth bleaching than
      conventional light sources with a low concentration of HP without causing thermal
      damage. Tooth bleaching using NAPP can become a major technique for in-office
      bleaching in the near future.

PMID- 23857659
TI  - Morphological characterization of the nasopalatine region in human fetuses and
      its association to pathologies.
AB  - The nasopalatine region is composed of structures such as the vomeronasal organ
      and nasopalatine duct. The nasopalatine duct may provide the communication of the
      mouth to the nasal cavity in human fetuses and can be obliterated in an adult
      human. Knowledge on the development of the nasopalatine region and nasopalatine
      duct in humans is necessary for understanding the morphology and etiopathogenesis
      of lesions that occur in this region. OBJECTIVE: The aim of the present study was
      to describe the morphological aspects of the nasopalatine region in human fetuses
      and correlate these aspects with the development of pathologies in this region.
      MATERIAL AND METHODS: Five human fetuses with no facial or palatine abnormalities
      were used for the acquisition of specimens from the nasopalatine region. After
      demineralization, the specimens were histologically processed. Histological cuts
      were stained with methylene blue to orient the cutting plane and hematoxylin
      eosin for the descriptive histological analysis. RESULTS: The age of the fetuses
      was 8.00, 8.25, 9.00 and 9.25 weeks, and it was not possible to determine the age
      in the last one. The incisive canal was observed in all specimens as an opening
      delimited laterally by the periosteum and connecting oral and nasal cavity. The
      nasopalatine duct is an epithelial structure with the greatest morphological
      variation, with either unilateral or bilateral occurrence and total patent,
      partial patent and islet forms. The vomeronasal organ is a bilateral epithelized
      structure located alongside the nasal septum above the incisive canal in all the
      fetuses. CONCLUSIONS: The incisive canal, nasopalatine duct and vomeronasal organ
      are distinct anatomic structures. The development of nasopalatine duct cysts may
      occur in all forms of the nasopalatine duct.

PMID- 23857660
TI  - Genetics of tooth agenesis: how to move the field forward.

PMID- 23857661
TI  - Temporomandibular joints in patients with rheumatoid arthritis using magnetic
      resonance imaging.
AB  - The aim of this study was to determine the relationship between the pathogenic
      duration of rheumatoid arthritis in joints other than the temporomandibular joint
      and bone and soft tissue involvement of the temporomandibular joint using
      magnetic resonance imaging. Twenty-six symptomatic patients diagnosed with
      rheumatoid arthritis were enrolled in this study. All patients were classified
      according to the duration of rheumatoid arthritis in joints other than the
      temporomandibular joint. The relationships between the duration of rheumatoid
      arthritis in these various joints and magnetic resonance findings in the
      temporomandibular joint were analyzed using the chi-square test. Bony changes in
      the mandibular condyle were observed in 43 of 52 (82.7 %) temporomandibular
      joints, but the frequency of such changes was not significantly correlated with
      the duration of rheumatoid arthritis in other joints. We found a significant
      correlation between the duration of rheumatoid arthritis in other joints and the
      type and number of bony changes in the mandibular condyle (P < 0.05). Superior
      disc positions were observed in 27 of 52 (51.9 %) temporomandibular joints. T2
      weighted images demonstrated effusion in the joint space in 38 of 52 (73.1 %)
      temporomandibular joints. A biplanar disc configuration was the most frequent
      configuration in all groups. The duration of rheumatoid arthritis in other joints
      was significantly correlated with the mobility of the mandibular condyle (P <
      0.05). The type and number of bony changes and mobility of the mandibular condyle
      showed significant relationships with the duration of rheumatoid arthritis in
      other joints in the body (P < 0.05).

PMID- 23857662
TI  - Immunoserological parameters in SLE: high-avidity anti-dsDNA detected by ELISA
      are the most closely associated with the disease activity.
AB  - We assessed the relationship between the serum levels of antibodies against
      double-stranded DNA (dsDNA), C1q, nucleosomes, histones, C3 and C4 complement
      components with one another, with organ involvement and overall disease activity
      in patients with systemic lupus erythematosus (SLE). One hundred seventy-five
      sera from 99 patients with SLE, 31 sera of patients with other connective tissue
      diseases, and 20 sera from healthy blood donors were tested. SLE disease activity
      was assessed by modified SLEDAI-2K (M-SLEDAI-2K), not including complement and
      anti-dsDNA descriptors. Anti-dsDNA antibodies were measured by indirect
      immunofluorescence on Crithidia luciliae (CLIFT), standard enzyme-linked
      immunosorbent assay (ELISA) and ELISA for high-avidity antibodies. The most
      significant risk factor for renal involvement were anti-C1q antibodies (OR =
      3.88, p < 0.05), high-avidity anti-dsDNA antibodies for polyserositis (OR = 7.99,
      p < 0.01), anti-histone antibodies for joint involvement (OR = 2.75, p < 0.05),
      and low C3 for cytopenia (OR = 11.96, p < 0.001) and mucocutaneous lesions (OR =
      3.32, p < 0.01). Multiple linear regression analysis showed that disease activity
      in SLE could be predicted by the levels of antibodies against dsDNA determined by
      standard (p < 0.05) and high-avidity (p < 0.001) ELISA, and inversely associated
      with concentration of C3 (p < 0.001). Using stepwise method, high-avidity anti
      dsDNA antibodies were found to be in the closest association to M-SLEDAI-2K.
      Moreover, positive test for high-avidity anti-dsDNA antibodies appeared as an
      independent risk factor for moderately to severely active disease (M-SLEDAI-2K>5)
      (OR = 5.5, p < 0.01). The presence of high-avidity anti-dsDNA antibodies
      represented a risk for renal, joint, and most importantly for serosal
      involvement. Our results suggest that simple and reliable ELISA for high-avidity
      anti-dsDNA antibodies is the test of good clinical utility for the assessment of
      global SLE activity.

PMID- 23857663
TI  - Dislocation of the extensor carpi ulnaris tendon in rheumatoid wrists using three
      dimensional computed tomographic imaging.
AB  - The purpose of this study was to evaluate dislocation of the extensor carpi
      ulnaris (ECU) tendon in patients with rheumatoid arthritis (RA) using three
      dimensional computed tomography (3DCT). We then determined the value of 3DCT for
      predicting spontaneous extensor tendon rupture. 3DCT images of 102 wrists from 96
      patients with RA were analyzed. Dislocation of the ECU tendon was evaluated from
      the 3DCT images with a soft tissue window. Dorsal subluxation of the ulnar head
      was evaluated as the dorsal subluxation ratio (DSR), and carpal supination was
      evaluated as the carpal supination angle (CSA) from the 3DCT images with a bone
      tissue window. Extensor tendon rupture was found in 43 of 102 wrists (42 %).
      Dislocation of the ECU tendon was found in 35 of 102 wrists (34 %). Dislocation
      of the ECU tendon was a strong risk factor for extensor tendon rupture in the
      multivariable logistic regression analysis, with an odds ratio of 26 (95 %
      confidence interval 7-99, p < 0.001). The DSR (p = 0.029) and CSA (p = 0.035)
      were significantly larger in wrists with a dislocated ECU tendon. Dislocation of
      the ECU tendon was well depicted using 3DCT images. It was strongly associated
      with extensor tendon rupture in the rheumatoid wrist.

PMID- 23857665
TI  - Benzenoid polycyclic hydrocarbons with an open-shell biradical ground state.
AB  - This Focus Review describes the recent progress, from both theoretical and
      experimental perspectives, on four types of benzenoid polycyclic hydrocarbons
      with an open-shell biradical ground state: 1) acenes, 2) periacenes and anthenes,
      3) zethrenes, and 4) extended p-quinodimethane derivatives. These interesting
      molecules have provided excellent platforms to investigate the electronic
      structures of nanographenes and represent promising candidates for the next
      generation of molecule-based materials in the field of electronics, spintronics,
      and non-linear optics. The focus of this article will be put on the structural
      significance, the physical properties relevant to the open-shell electronic
      configurations, and potential applications.

PMID- 23857664
TI  - Questionnaire survey evaluating disease-related knowledge for 149 primary gout
      patients and 184 doctors in South China.
AB  - This study aims to investigate the disease-related knowledge of gout patients and
      doctors in south China and to identify the important targets of education for
      patients and doctors. A cross-section survey of 154 primary gout patients and 185
      doctors who may see gout patients was conducted with a modified questionnaire
      with ten items of gout-related knowledge. The participants were considered to
      have gout-related knowledge if he or she correctly answered seven or more items.
      One hundred and forty-nine valid questionnaires from patients, 33 from
      rheumatology physicians, and 151 from non-rheumatology doctors were collected for
      statistical analysis. The mean correctly answered items of three groups were 6.6
      +/- 2.2, 9.6 +/- 0.53, and 8.0 +/- 1.4, with rate of being considered to have
      knowledge about gout 51.7, 100, and 90.1 %, respectively (P < 0.05). The correct
      answer rate for each particular item was over 80 % in the rheumatology physician
      group. Patients or non-rheumatology doctors knew the optimal serum uric acid
      (sUA) level (48.3 vs 55.6 %), the need to take lifelong urate-lowering drugs
      (29.5 vs 43.6 %), that allopurinol is a urate-lowering drug (55.7 vs 76.0 %), and
      how to prevent attacks induced by urate-lowering therapy (ULT) (60.4 vs 74.0 %).
      Logistic regression showed that higher education predicted which patients had
      gout-related knowledge. Both the gout patients and non-rheumatology doctors in
      south China had poor knowledge on ULT. Since many gout patients do not see
      rheumatologists, our data suggest that further education should focus on patients
      and non-rheumatologists and emphasize the use of urate-lowering drugs, treatment
      duration, the target sUA level, and prophylaxis against acute attacks.

PMID- 23857666
TI  - Assessment of navigation control strategy for magnetotactic bacteria in
      microchannel: toward targeting solid tumors.
AB  - This paper presents a Magnetotactic Bacteria (MTB) navigation and aggregation
      technique that allows targeting without prior knowledge of the exact architecture
      of the vessels network. The MTB's active motility combined with magnetotaxism
      (their ability to swim following the magnetic field direction) offer new
      possibilities for the delivery of drugs to tumors. Many tumor microenvironment
      parameters such as the malformed angiogenesis capillaries, the heterogeneous
      blood flow, and the high interstitial pressure affect the delivery of blood-borne
      drugs to the tumor. Microorganisms used as microcarriers might be helpful in
      bypassing these limitations while helping to uniformly distribute the drug in the
      targeted area. Since the angiogenesis network of blood vessels that the tumors
      recruit is highly disorganized and unpredictable, the magnetic control method
      adopted account for these parameters to achieve targeting. We demonstrate the
      effectiveness of the proposed method using a microchannel network offering a
      complex pattern considered as a worst-case navigation situation. Besides targeted
      drug delivery to tumor sites using bacterial carrier, aggregation of
      microorganisms is required for micromanipulation and microassembly. 

PMID- 23857667
TI  - Near-contiguous spin echo imaging using matched-phase RF and its application in
      velocity-selective arterial spin labeling.
AB  - PURPOSE: The minimum slice spacing in multislice imaging is limited by inter
      slice crosstalk due to an imperfect slice profile. This study sought to minimize
      the slice spacing using matched-phase RF pulses and demonstrate its application
      in cerebral blood flow imaging using velocity-selective arterial spin labeling.
      METHODS: A spin-echo matched-phase 90 degrees -180 degrees  RF pair was designed
      using Shinnar-Le Roux algorithm in order to improve the slice profile of
      longitudinal magnetization, which plays a more critical role in creating
      interslice crosstalk than transverse magnetization. Both transverse and
      longitudinal slice profiles were compared between matched-phase RF and sinc-based
      RF pulses in simulations and measurements. Velocity-selective arterial spin
      labeling was performed in normal volunteers using both RF pulses and standard
      deviation of cerebral blood flow time series was calculated to examine ASL signal
      stability. RESULTS: Using designed matched-phase RF, the longitudinal slice
      profile was sharpened without signal-to-noise ratio loss. In velocity-selective
      arterial spin labeling imaging, the temporal standard deviation of cerebral blood
      flow measurements was reduced from 48 mL/100 g/min to 32 mL/100 g/min by 33%
      using matched-phase RF pulses, and as a result, cerebral blood flow image quality
      improved. CONCLUSION: This study reports that near-contiguous multislice imaging
      can be achieved using matched-phase RF pulses without compromising signal-to
      noise ratio and signal stability.

PMID- 23857668
TI  - NIR-sensitive poly(3,4-ethylenedioxyselenophene) derivatives for transparent
      photo-thermo-electric converters.
AB  - Electrochromism, photothermal effect, and thermoelectric properties of hexyl
      derivatized poly(3,4-ethylenedioxyselenophene) are investigated by precisely
      controlling the morphology. These properties are clearly demonstrated by
      controlling the applied electrical potential of the polymer films. Especially,
      the doped polymer film at -0.1 V reveals the highest photothermal conversion
      efficiency and a power factor of 42.5% and 354.7 MUW m(-1) K(-2) , respectively.
      Efficient visible to near-infrared absorption, photon to heat, and heat to
      electric conversion has been realized in one film that could benefit in
      exploiting multifunctional film displays, invisible NIR sensors, photodynamic
      theragnosis, and thermoelectric devices. 

PMID- 23857669
TI  - Relationship of psychological symptoms, antipsychotics and social data with
      psychosocial function in schizophrenia patients in Malaysia.
AB  - INTRODUCTION: The present study investigated the relationship between
      psychological symptoms and psychosocial function and the role of relevant
      sociodemographic data and antipsychotic use in the prediction of psychosocial
      function among multiracial schizophrenia outpatients in Malaysia. METHODS: A
      total of 223 participants were recruited in this cross-sectional study conducted
      from December 2010 to April 2011. Psychological symptoms were assessed using the
      Positive and Negative Syndrome Scale whilst the psychosocial function was
      assessed using the Personal and Social Performance scale. Sociodemographic and
      treatment variables were gathered through interview or review of the medical
      records. RESULTS: All dimensions of psychosocial functions were inversely
      correlated with Positive and Negative Syndrome Scale sub-domains. Only the
      disorganization sub-domain significantly predicts all dimensions of psychosocial
      function. For social data, body mass index and employment status were significant
      predictors of all dimensions of psychosocial functions. Typical antipsychotics
      significantly predict social function negatively as compared to sulpiride (beta =
      -0.152, P = 0.028). DISCUSSION: We found that the relationship between
      psychological symptoms and psychosocial functions were relatively consistent with
      the findings from the Caucasian population. Additionally, disorganization was the
      only significant predictor of all dimensions of psychosocial functions. This
      further emphasized the importance of cognition in psychosocial function. The
      roles of sulpiride, body mass index and employment status as predictors of
      psychosocial function were also discussed.

PMID- 23857670
TI  - Assessment of prospective memory in schizophrenia using the Chinese version of
      the Cambridge Prospective Memory Test: a controlled study.
AB  - INTRODUCTION: Data on the psychometric assessment of prospective memory (PM) are
      limited. The Cambridge Prospective Memory Test (CAMPROMPT) and its Chinese
      version (CAMPROMPT-C) have been applied to a variety of clinical conditions
      except for chronic schizophrenia. This controlled study explored the clinical
      utility of the CAMPROMPT-C in patients with schizophrenia by comparing their PM
      performance with that of normal controls. METHODS: Forty-four schizophrenia
      patients and 44 normal controls formed the study sample. Sociodemographic
      characteristics, PM, retrospective memory, and intelligence were measured in all
      subjects. Patients' psychopathology was rated with a standardized instrument.
      RESULTS: Patients performed worse than normal controls on both the sum and
      subscale scores of the CAMPROMPT-C. Patients had comparable performances in PM
      subtypes. Bivariate analyses revealed that education level, intelligence, and
      retrospective memory were associated with PM functions. DISCUSSION: The study
      supports the clinical utility of the CAMPROMPT-C in chronic schizophrenia and
      corroborated the significant relationship between PM and education, intelligence,
      and retrospective memory.

PMID- 23857671
TI  - The CX3CL1/CX3CR1 reprograms glucose metabolism through HIF-1 pathway in
      pancreatic adenocarcinoma.
AB  - One of the hallmarks of cancer is revised glucose metabolism that promotes cell
      survival and proliferation. In pancreatic cancer, the regulatory mechanism of
      glucose metabolism remains to be elucidated. In this study, we found that CX3CR1
      is expressed in pancreatic cancer cells lines. Exogenous or transfected CX3CL1
      increased glucose uptake and lactate secretion. CX3CL1 stimulated HIF-1
      expression through PI3K/Akt and MAPK pathways. Furthermore, knockdown of HIF-1
      blocked CX3CL1-modified glucose metabolism in pancreatic adenocarcinoma cells. In
      conclusion, the CX3CL1/CX3CR1 reprograms glucose metabolism through HIF-1 pathway
      in pancreatic cancer cells.

PMID- 23857672
TI  - Quantification of a proteotypic peptide from protein C inhibitor by liquid
      chromatography-free SISCAPA-MALDI mass spectrometry: application to
      identification of recurrence of prostate cancer.
AB  - BACKGROUND: Biomarker validation remains one of the most challenging constraints
      to the development of new diagnostic assays. To facilitate biomarker validation,
      we previously developed a chromatography-free stable isotope standards and
      capture by antipeptide antibodies (SISCAPA)-MALDI assay allowing rapid, high
      throughput quantification of protein analytes in large sample sets. Here we
      applied this assay to the measurement of a surrogate proteotypic peptide from
      protein C inhibitor (PCI) in sera from patients with prostate cancer. METHODS: A
      2-plex SISCAPA-MALDI assay for quantification of proteotypic peptides from PCI
      and soluble transferrin receptor (sTfR) was used to measure these peptides in 159
      trypsin-digested sera collected from 51 patients with prostate cancer. These
      patients had been treated with radiation with or without neoadjuvant androgen
      deprivation. RESULTS: Patients who experienced biochemical recurrence of prostate
      cancer showed decreased serum concentrations of the PCI peptide analyte within 18
      months of treatment. The PCI peptide concentrations remained increased in the
      sera of patients who did not experience cancer recurrence. Prostate-specific
      antigen concentrations had no predictive value during the same time period.
      CONCLUSIONS: The high-throughput, liquid chromatography-free SISCAPA-MALDI assay
      is capable of rapid quantification of proteotypic PCI and sTfR peptide analytes
      in complex serum samples. Decreased serum concentrations of the PCI peptide were
      found to be related to recurrence of prostate cancer in patients treated with
      radiation with or without hormone therapy. However, a larger cohort of patients
      will be required for unequivocal validation of the PCI peptide as a biomarker for
      clinical use.

PMID- 23857673
TI  - Noninvasive prenatal methylomic analysis by genomewide bisulfite sequencing of
      maternal plasma DNA.
AB  - BACKGROUND: Epigenetic mechanisms play an important role in prenatal development,
      but fetal tissues are not readily accessible. Fetal DNA molecules are present in
      maternal plasma and can be analyzed noninvasively. METHODS: We applied genomewide
      bisulfite sequencing via 2 approaches to analyze the methylation profile of
      maternal plasma DNA at single-nucleotide resolution. The first approach used
      maternal blood samples and polymorphic differences between the mother and fetus
      to analyze the fetal methylome across the genome. The second approach used the
      methylation profile of maternal blood cells and the fractional fetal DNA
      concentration in maternal plasma to deduce the placental methylomic profile from
      maternal plasma DNA-sequencing data. RESULTS: Because of the noninvasive nature
      of these approaches, we were able to serially assess the methylation profiles of
      fetal, placental, and maternal plasma with maternal blood samples collected in
      the first and third trimesters and after delivery. Gestation-related changes were
      observed. The fetal methylation profile deduced from maternal plasma data
      resembled that of the placental methylome, both on a genomewide level and per CpG
      site. Imprinted genes and differentially methylated regions were identified from
      the maternal plasma data. We demonstrated one potential clinical application of
      maternal plasma bisulfite sequencing with the successful detection of fetal
      trisomy 21. CONCLUSIONS: We successfully analyzed fetal and placental methylomes
      on a genomewide scale, noninvasively and serially. This development offers a
      powerful method for research, biomarker discovery, and clinical testing for
      pregnancy-related disorders.

PMID- 23857674
TI  - Prenatal diagnosis of chromosome abnormalities: past, present, and future.

PMID- 23857675
TI  - Preliminary study of patterns of medication use for depression treatment in
      China.
AB  - This systematic review investigated drug utilization for depression and assessed
      trends in prescriptions in China. Major Western and Chinese electronic databases
      were searched without language restriction for studies reporting defined daily
      doses. A total of 76 studies published between 2000 and 2010 reporting data on
      prescriptions for depression in China between 1996 and 2008 were included. All
      studies were published in Chinese. Most trials were conducted in urban areas in
      south and east China. Twenty-nine drugs were reported as antidepressants. On the
      basis of defined daily doses, melitracen/flupentixol combination, fluoxetine, and
      paroxetine were the most frequently prescribed compounds. According to published
      evidence, selective serotonin reuptake inhibitors have become the most commonly
      prescribed class of antidepressant drugs in China. 

PMID- 23857676
TI  - Luminescent polymer consisting of 9,12-linked o-carborane.
AB  - The synthesis of novel luminescent polymer containing p-phenylene-ethynylene and
      9,12-linked o-carborane units alternately in the main chain is reported. The
      obtained polymer exhibits intense blue photoluminescence, providing the first
      insights into the optical properties of a 9,12-disubstituted o-carborane dye. pi
      Conjugated substituent at 9 and/or 12-positions in o-carborane is electrically
      independent, and both the HOMO and the LUMO levels slightly increase, whereas
      LUMO of the pi-conjugated substituent at 1 and/or 2-positions in o-carborane
      decrease. Thus, it is deduced that polymers consisting of the 9,12-linked o
      carborane unit are able to be applied as light-emitting materials.

PMID- 23857677
TI  - Green methodology based on dispersive liquid-liquid microextraction and micellar
      electrokinetic chromatography for 5-nitroimidazole analysis in water samples.
AB  - Dispersive liquid-liquid microextraction has been proposed as an extraction
      technique combined with micellar electrokinetic chromatography (MEKC) for the
      analysis of eight 5-nitroimidazole compounds, including some metabolites, in
      water samples. Determination has been carried out using a diode array detector,
      employing 20 mM sodium phosphate and 150 mM SDS as separation buffer. Separation
      has taken place under a voltage of 25 kV and a temperature of 20 degrees C.
      Samples were prepared in a buffer without micelles and they were hydrodynamically
      injected at 50 mbar for 25 s, producing a sweeping effect on the analytes for
      increasing sensitivity. Different factors involved in the dispersive liquid
      liquid microextraction procedure were optimized, such as sample pH, nature, and
      volume of extraction and dispersive solvents in the mixture, percentage of NaCl
      added to sample and shaking time after the injection of the extraction and
      dispersive solvents. The method was characterized for water samples, achieving
      detection limits lower than 2.4 MUg/L. Trueness was checked in river, tap, and
      bottled water. Dispersive liquid-liquid microextraction combined with MEKC
      constitutes an easy, cheap, and green alternative for 5-nitroimidazole analysis
      in environmental water samples. 

PMID- 23857678
TI  - Ultrastructural characteristics of the spermatogenesis during the four phases of
      the annual reproductive cycle of the black myotis bat, Myotis nigricans
      (Chiroptera: Vespertilionidae).
AB  - Myotis nigricans is an endemic species of vespertilionid bat, from the
      Neotropical region, that resembles temperate zone bats in their reproductive
      cycle; presenting an annual reproductive cycle with two periods of testicular
      regression, which are not linked to the apoptotic process and seems to be not
      directly linked to any seasonal abiotic variation. Thus, this study aimed to
      ultrastructurally evaluate their reproductive cycle. The process of testicular
      regression could be divided into four periods: active; regressing; regressed and
      recrudescence; with all presenting distinct characteristics. The active period
      was similar to that of other bats, presenting the complete occurrence of
      spermatogenesis, with three main types of spermatogonia (A(d), A(p), and B) and
      12 steps in spermatid differentiation; however, it differed in having the outer
      dense fibers 1, 5, 6, and 9 larger than the others. These three types of
      spermatogonia undergo considerable morphologic changes from regressing to the
      regressed period, and in the recrudescence, they return to the basic morphology,
      which reactivates spermatogenesis. In conclusion, our study described the process
      of spermatogenesis, the ultrastructure of the spermatozoa and the distinct
      morphologic variations in the ultrastructure of the testicular cells of M.
      nigricans during the four different periods of its annual reproductive cycle.

PMID- 23857679
TI  - Synthesis of uniform poly(d,l-lactide) and poly(d,l-lactide-co-glycolide)
      microspheres using a microfluidic chip for comparison.
AB  - Applications of poly(l-lactide) (PLA) and poly(d,l-lactide-co-glycolide) (PLGA)
      microspheres are widely used in the biomedical and pharmaceutical fields. The
      effects of PLA/PLGA on microsphere properties when using conventional particulate
      preparation methods are not easily defined due to the uncontrollable particle
      size and size distribution. This study was aimed to synthesize uniform PLA and
      PLGA microspheres using a phenol formaldehyde resin-based microfluidic chip,
      which has the advantage of being solvent-resistant, flexible, and is readily
      disassembled for cleaning. The proposed chip can rapidly fabricate reproducible
      PLA and PLGA microspheres. Uniform emulsion droplets can be achieved by
      hydrodynamic flow focusing. After solvent evaporation, the free-flowing PLA and
      PLGA microspheres have a high level of morphological uniformity and size,
      allowing for a clear comparison of material effects. The results indicate that
      the sizes of the PLA and PLGA microspheres for the various flow rates of
      dispersed/continuous phases are very similar. The PLA/PLGA materials do not have
      a significant effect on particle size, but the particle surface indicates a
      different morphology. The result of the cytotoxicity evaluation shows no
      difference between PLA and PLGA and ensures the biocompatibility of both prepared
      PLA and PLGA microspheres for biomedical and pharmaceutical applications in the
      future. 

PMID- 23857680
TI  - Impact of pulmonary rehabilitation on quality of life and functional capacity in
      patients on waiting lists for lung transplantation.
AB  - OBJECTIVE: To investigate the impact of a pulmonary rehabilitation program on the
      functional capacity and on the quality of life of patients on waiting lists for
      lung transplantation. METHODS: Patients on lung transplant waiting lists were
      referred to a pulmonary rehabilitation program consisting of 36 sessions. Before
      and after the program, participating patients were evaluated with the six-minute
      walk test and the Medical Outcomes Study 36-item Short-Form Health Survey (SF
      36). The pulmonary rehabilitation program involved muscle strengthening
      exercises, aerobic training, clinical evaluation, psychiatric evaluation,
      nutritional counseling, social assistance, and educational lectures. RESULTS: Of
      the 112 patients initially referred to the program, 58 completed it. The mean age
      of the participants was 46 +/- 14 years, and females accounted for 52%. Of those
      58 patients, 37 (47%) had pulmonary fibrosis, 13 (22%) had pulmonary emphysema,
      and 18 (31%) had other types of advanced lung disease. The six-minute walk
      distance was significantly greater after the program than before (439 +/- 114 m
      vs. 367 +/- 136 m, p = 0.001), the mean increase being 72 m. There were
      significant point increases in the scores on the following SF-36 domains:
      physical functioning, up 22 (p = 0.001), role-physical, up 10 (p = 0.045);
      vitality, up 10 (p < 0.001); social functioning, up 15 (p = 0.001); and mental
      health, up 8 (p = 0.001). CONCLUSIONS: Pulmonary rehabilitation had a positive
      impact on exercise capacity and quality of life in patients on lung transplant
      waiting lists.

PMID- 23857682
TI  - Alveolar hemorrhage after parenteral injection of industrial silicone.

PMID- 23857681
TI  - Evaluation of atopy in patients with COPD.
AB  - OBJECTIVE: To determine the prevalence of atopy and to evaluate clinical,
      laboratory, and radiological profiles in patients with COPD. METHODS: This was a
      cross-sectional study involving outpatients with stable COPD (defined by the
      clinical history and a post-bronchodilator FEV1/FVC < 70% of the predicted
      value). The patients completed a questionnaire regarding clinical characteristics
      and atopy, after which they underwent nasal lavage cytology, skin prick testing,
      chest X-rays, arterial blood gas analyses, and determination of total serum IgE.
      RESULTS: Of the 149 subjects studied, 53 (35.6%), 49 (32.8%), and 88 (59.1%)
      presented with nasal eosinophilia, a positive skin prick test result, and
      symptoms of allergic rhinitis, respectively. Correspondence analysis confirmed
      these findings, showing two distinct patterns of disease expression: atopy in
      patients with COPD that was less severe; and no evidence of atopy in those with
      COPD that was more severe (reduced FEV1 and hyperinflation). There was a
      statistically significant association between nasal eosinophilia and a positive
      bronchodilator response. CONCLUSIONS: Using simple and reproducible methods, we
      were able to show that there is a high frequency of atopy in patients with COPD.
      Monitoring inflammation in the upper airways can be a useful tool for evaluating
      respiratory diseases in the elderly and in those with concomitant asthma and
      COPD, a clinical entity not yet fully understood.

PMID- 23857683
TI  - Performance comparison between the mycobacteria growth indicator tube system and
      Lowenstein-Jensen medium in the routine detection of Mycobacterium tuberculosis
      at public health care facilities in Rio de Janeiro, Brazil: preliminary results
      of a pragmatic clinical trial.
AB  - In view of the fact that the World Health Organization has recommended the use of
      the mycobacteria growth indicator tube (MGIT) 960 system for the diagnosis of
      tuberculosis and that there is as yet no evidence regarding the clinical impact
      of its use in health care systems, we conducted a pragmatic clinical trial to
      evaluate the clinical performance and cost-effectiveness of the use of MGIT 960
      at two health care facilities in the city of Rio de Janeiro, Brazil, where the
      incidence of tuberculosis is high. Here, we summarize the methodology and
      preliminary results of the trial. (ISRCTN.org Identifier: ISRCTN79888843
      [http://isrctn.org/]) In view of the fact that the World Health Organization has
      recommended the use of the mycobacteria growth indicator tube (MGIT) 960 system
      for the diagnosis of tuberculosis and that there is as yet no evidence regarding
      the clinical impact of its use in health care systems, we conducted a pragmatic
      clinical trial to evaluate the clinical performance and cost-effectiveness of the
      use of MGIT 960 at two health care facilities in the city of Rio de Janeiro,
      Brazil, where the incidence of tuberculosis is high. Here, we summarize the
      methodology and preliminary results of the trial. (ISRCTN.org Identifier:
      ISRCTN79888843 [http://isrctn.org/]). 

PMID- 23857684
TI  - Characteristics of tuberculosis in the state of Minas Gerais, Brazil: 2002-2009.
AB  - OBJECTIVE: To analyze the profile of tuberculosis cases reported between 2002 and
      2009 in the state of Minas Gerais, Brazil, according to sociodemographic,
      clinical, and laboratory characteristics, as well as to comorbidities and
      mortality. METHODS: This was a descriptive, epidemiological study based on data
      obtained from the Brazilian Case Registry Database and the Brazilian Mortality
      Database for the 2002-2009 period. RESULTS: There were 47,285 reported cases of
      tuberculosis, corresponding to a mean incidence of 22.3/100,000 population. The
      individuals diagnosed with tuberculosis were predominantly in the 20- to 49-year
      age bracket and male (62.4% and 67.0%, respectively). Individuals with a low
      level of education accounted for 18.5% of the cases. New cases, cases of
      recurrence, and cases of retreatment accounted for 83.7%, 5.7%, 5.7%,
      respectively. The rates of cure and treatment noncompliance were 66.2% and 11.2%,
      respectively; multidrug-resistant tuberculosis was identified in 0.2% of the
      cases; and the mortality rate was 12.9%. The directly observed treatment, short
      course (DOTS) strategy was applied in 21.8% of the cases. Sputum smear microscopy
      and culture were performed in only 73.9% and 12.9% of the cases, respectively.
      Chest X-rays were performed in 90.5% of the cases. Pulmonary tuberculosis was the
      predominant form (in 83.9%). Comorbidity with alcoholism, HIV infection, and
      diabetes mellitus were identified in 17.2%, 8.3%, and 3.8%, respectively.
      CONCLUSIONS: During the study period, the numbers of new cases, cases of
      treatment noncompliance, and deaths were high, comorbidities were common, and
      there was a failure to perform adequately basic tests for the diagnosis of
      tuberculosis. Multidisciplinary approaches, expanded use of the DOTS strategy,
      better knowledge of the distribution of tuberculosis, and improvements in the
      databases are needed in order to achieve better control of the disease in the
      state of Minas Gerais.

PMID- 23857686
TI  - Smoke inhalation injury during enclosed-space fires: an update.
AB  - In view of the tragic fire at a nightclub in the city of Santa Maria, Brazil,
      which culminated in the sudden death of 232 young people, we decided to review
      the literature regarding smoke inhalation injury caused by enclosed-space fires,
      which can be divided into direct thermal damage, carbon monoxide poisoning, and
      cyanide poisoning. Such injuries often call for immediate orotracheal intubation,
      either due to acute airway obstruction or due to a reduced level of
      consciousness. The diagnosis and the severity of the thermal injury can be
      determined by fiberoptic bronchoscopy. The levels of gases and gas by-products in
      the bloodstream should be assessed as rapidly as possible, even while still at
      the scene of the incident. First responders can also treat carbon monoxide
      poisoning, with immediate administration of oxygen at 100%, as well as cyanide
      poisoning, with oxygen therapy and hydroxocobalamin injection. 

PMID- 23857687
TI  - Aspergillus fumigatus fungus ball in the native lung after single lung
      transplantation.

PMID- 23857688
TI  - Influenza A (H1N1) pneumonia: HRCT findings.
AB  - OBJECTIVE: To describe aspects found on HRCT scans of the chest in patients
      infected with the influenza A (H1N1) virus. METHODS: We retrospectively analyzed
      the HRCT scans of 71 patients (38 females and 33 males) with H1N1 infection,
      confirmed through laboratory tests, between July and September of 2009. The HRCT
      scans were interpreted by two thoracic radiologists independently, and in case of
      disagreement, the decisions were made by consensus. RESULTS: The most common HRCT
      findings were ground-glass opacities (85%), consolidation (64%), or a combination
      of ground-glass opacities and consolidation (58%). Other findings were airspace
      nodules (25%), bronchial wall thickening (25%), interlobular septal thickening
      (21%), crazy-paving pattern (15%), perilobular pattern (3%), and air trapping
      (3%). The findings were frequently bilateral (89%), with a random distribution
      (68%). Pleural effusion, when observed, was typically minimal. No lymphadenopathy
      was identified. CONCLUSIONS: The most common findings were ground-glass opacities
      and consolidations, or a combination of both. Involvement was commonly bilateral
      with no axial or craniocaudal predominance in the distribution. Although the
      major tomographic findings in H1N1 infection are nonspecific, it is important to
      recognize such findings in order to include infection with the H1N1 virus in the
      differential diagnosis of respiratory symptoms.

PMID- 23857689
TI  - Inhaler use in adolescents and adults with self-reported physician-diagnosed
      asthma, bronchitis, or emphysema in the city of Pelotas, Brazil.
AB  - OBJECTIVE: To evaluate the characteristics of users of inhalers and the
      prevalence of inhaler use among adolescents and adults with self-reported
      physician-diagnosed asthma, bronchitis, or emphysema. METHODS: A population-based
      study conducted in the city of Pelotas, Brazil, involving 3,670 subjects >= 10
      years of age, evaluated with a questionnaire. RESULTS: Approximately 10% of the
      sample reported at least one of the respiratory diseases studied. Among those
      individuals, 59% reported respiratory symptoms in the last year, and, of those,
      only half reported using inhalers. The use of inhalers differed significantly by
      socioeconomic status (39% and 61% for the lowest and the highest, respectively, p
      = 0.01). The frequency of inhaler use did not differ by gender or age. Among the
      individuals reporting emphysema and inhaler use, the use of the bronchodilator
      corticosteroid combination was more common than was that of a bronchodilator
      alone. Only among the individuals reporting physician-diagnosed asthma and
      current symptoms was the proportion of inhaler users higher than 50%.
      CONCLUSIONS: In our sample, inhalers were underutilized, and the type of
      medication used by the individuals who reported emphysema does not seem to be in
      accordance with the consensus recommendations.

PMID- 23857690
TI  - Effects of an outpatient education program in patients with uncontrolled asthma.
AB  - OBJECTIVE: To evaluate the effects of an outpatient education program in patients
      with uncontrolled asthma. METHODS: This was an uncontrolled study evaluating an
      educational intervention and involving patients with uncontrolled asthma >= 14
      years of age. The participants completed a questionnaire designed to assess the
      level of asthma control, the inhalation technique, and quality of life. All of
      the patients underwent pulmonary function testing, after which they participated
      in an education program consisting of one 45-min face-to-face session, followed
      by phone interviews at two, four, and eight weeks. The participants were
      reevaluated after three months. RESULTS: Sixty-three patients completed the
      study. There was a significant improvement in the level of asthma control (p <
      0.001). Of the 63 patients, 28 (44.4%) and 6 (9.5%) were classified as having
      partially controlled asthma and controlled asthma, respectively. The mean FEV1
      was 63.0 +/- 20.0% and 68.5 +/- 21.2% of the predicted value prior to and after
      the educational intervention, respectively (p = 0.002), and all of the quality of
      life scores improved (p < 0.05 for all). The same was true for the proportion of
      patients prior to and after the educational intervention using the proper
      inhalation technique when using metered dose inhalers (15.4% vs. 46.2%; p = 0.02)
      and dry powder inhalers (21.3% vs. 76.6%; p < 0.001). The logistic regression
      analysis revealed that an incorrect inhalation technique identified during the
      first evaluation was independently associated with a favorable response to the
      educational intervention. CONCLUSIONS: This study suggests that an outpatient
      education program for asthma patients improves the level of asthma control, lung
      function parameters, and quality of life. An incorrect inhalation technique
      identified during the first evaluation was predictive of a favorable response to
      the educational intervention.

PMID- 23857691
TI  - Pulmonary capillary hemangiomatosis: an uncommon cause of pulmonary hypertension.

PMID- 23857692
TI  - Does thromboprophylaxis prevent venous thromboembolism after major orthopedic
      surgery?
AB  - OBJECTIVE: Pulmonary embolism (PE) is an important complication of major
      orthopedic surgery. The aim of this study was to evaluate the incidence of venous
      thromboembolism (VTE) and factors influencing the development of VTE in patients
      undergoing major orthopedic surgery in a university hospital. METHODS: Patients
      who underwent major orthopedic surgery (hip arthroplasty, knee arthroplasty, or
      femur fracture repair) between February of 2006 and June of 2012 were
      retrospectively included in the study. The incidences of PE and deep vein
      thrombosis (DVT) were evaluated, as were the factors influencing their
      development, such as type of operation, age, and comorbidities. RESULTS: We
      reviewed the medical records of 1,306 patients. The proportions of knee
      arthroplasty, hip arthroplasty, and femur fracture repair were 63.4%, 29.9%, and
      6.7%, respectively. The cumulative incidence of PE and DVT in patients undergoing
      major orthopedic surgery was 1.99% and 2.22%, respectively. Most of the patients
      presented with PE and DVT (61.5% and 72.4%, respectively) within the first 72 h
      after surgery. Patients undergoing femur fracture repair, those aged >= 65 years,
      and bedridden patients were at a higher risk for developing VTE. CONCLUSIONS: Our
      results show that VTE was a significant complication of major orthopedic surgery,
      despite the use of thromboprophylaxis. Clinicians should be aware of VTE,
      especially during the perioperative period and in bedridden, elderly patients (>=
      65 years of age).

PMID- 23857693
TI  - Pneumothorax as a complication of lung volume recruitment.
AB  - Lung volume recruitment involves deep inflation techniques to achieve maximum
      insufflation capacity in patients with respiratory muscle weakness, in order to
      increase peak cough flow, thus helping to maintain airway patency and improve
      ventilation. One of these techniques is air stacking, in which a manual
      resuscitator is used in order to inflate the lungs. Although intrathoracic
      pressures can rise considerably, there have been no reports of respiratory
      complications due to air stacking. However, reaching maximum insufflation
      capacity is not recommended in patients with known structural abnormalities of
      the lungs or chronic obstructive airway disease. We report the case of a 72-year
      old woman who had poliomyelitis as a child, developed torsion scoliosis and post
      polio syndrome, and had periodic but infrequent asthma attacks. After performing
      air stacking for 3 years, the patient suddenly developed a pneumothorax,
      indicating that this technique should be used with caution or not at all in
      patients with a known pulmonary pathology. 

PMID- 23857694
TI  - Exacerbations of COPD and symptoms of gastroesophageal reflux: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To examine the relationship between gastroesophageal reflux (GER) and
      COPD exacerbations. METHODS: We conducted a systematic search of various
      electronic databases for articles published up through December of 2012. Studies
      considered eligible for inclusion were those dealing with COPD, COPD
      exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER
      vs. controls); and describing relative risks (RRs) and prevalence ratios-or ORs
      and their respective 95% CIs (or presenting enough data to allow further
      calculations) for the association between GER and COPD-as well as exacerbation
      rates. Using a standardized form, we extracted data related to the study design;
      criteria for GER diagnosis; age, gender, and number of participants;
      randomization method; severity scores; methods of evaluating GER symptoms;
      criteria for defining exacerbations; exacerbation rates (hospitalizations, ER
      visits, unscheduled clinic visits, prednisone use, and antibiotic use); GER
      symptoms in COPD group vs. controls; mean number of COPD exacerbations (with
      symptoms vs. without symptoms); annual frequency of exacerbations; GER treatment;
      and severity of airflow obstruction. RESULTS: Overall, GER was clearly identified
      as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94), with an
      increased mean number of exacerbations per year (mean difference: 0.79; 95% CI:
      0.22-1.36). The prevalence of GER was significantly higher in patients with COPD
      than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001). CONCLUSIONS:
      GER is a risk factor for COPD exacerbations. The role of GER in COPD management
      should be studied in greater detail.

PMID- 23857695
TI  - Extubation failure influences clinical and functional outcomes in patients with
      traumatic brain injury.
AB  - OBJECTIVE: To evaluate the association between extubation failure and outcomes
      (clinical and functional) in patients with traumatic brain injury (TBI). METHODS:
      A prospective cohort study involving 311 consecutive patients with TBI. The
      patients were divided into two groups according to extubation outcome: extubation
      success; and extubation failure (defined as reintubation within 48 h after
      extubation). A multivariate model was developed in order to determine whether
      extubation failure was an independent predictor of in-hospital mortality.
      RESULTS: The mean age was 35.7 +/- 13.8 years. Males accounted for 92.3%. The
      incidence of extubation failure was 13.8%. In-hospital mortality was 4.5% and
      20.9% in successfully extubated patients and in those with extubation failure,
      respectively (p = 0.001). Tracheostomy was more common in the extubation failure
      group (55.8% vs. 1.9%; p < 0.001). The median length of hospital stay was
      significantly greater in the extubation failure group than in the extubation
      success group (44 days vs. 27 days; p = 0.002). Functional status at discharge
      was worse among the patients in the extubation failure group. The multivariate
      analysis showed that extubation failure was an independent predictor of in
      hospital mortality (OR = 4.96; 95% CI, 1.86-13.22). CONCLUSIONS: In patients with
      TBI, extubation failure appears to lengthen hospital stays; to increase the
      frequency of tracheostomy and of pulmonary complications; to worsen functional
      outcomes; and to increase mortality.

PMID- 23857696
TI  - Is gastro-oesophageal reflux associated with COPD exacerbations?

PMID- 23857697
TI  - Risk factors for infection with multidrug-resistant bacteria in non-ventilated
      patients with hospital-acquired pneumonia.
AB  - OBJECTIVE: To identify risk factors for the development of hospital-acquired
      pneumonia (HAP) caused by multidrug-resistant (MDR) bacteria in non-ventilated
      patients. METHODS: This was a retrospective observational cohort study conducted
      over a three-year period at a tertiary-care teaching hospital. We included only
      non-ventilated patients diagnosed with HAP and presenting with positive bacterial
      cultures. Categorical variables were compared with chi-square test. Logistic
      regression analysis was used to determine risk factors for HAP caused by MDR
      bacteria. RESULTS: Of the 140 patients diagnosed with HAP, 59 (42.1%) were
      infected with MDR strains. Among the patients infected with methicillin-resistant
      Staphylococcus aureus and those infected with methicillin-susceptible S. aureus,
      mortality was 45.9% and 50.0%, respectively (p = 0.763). Among the patients
      infected with MDR and those infected with non-MDR gram-negative bacilli,
      mortality was 45.8% and 38.3%, respectively (p = 0.527). Univariate analysis
      identified the following risk factors for infection with MDR bacteria: COPD;
      congestive heart failure; chronic renal failure; dialysis; urinary
      catheterization; extrapulmonary infection; and use of antimicrobial therapy
      within the last 10 days before the diagnosis of HAP. Multivariate analysis showed
      that the use of antibiotics within the last 10 days before the diagnosis of HAP
      was the only independent predictor of infection with MDR bacteria (OR = 3.45; 95%
      CI: 1.56-7.61; p = 0.002). CONCLUSIONS: In this single-center study, the use of
      broad-spectrum antibiotics within the last 10 days before the diagnosis of HAP
      was the only independent predictor of infection with MDR bacteria in non
      ventilated patients with HAP.

PMID- 23857698
TI  - Pleuropulmonary complications related to pulmonary instillation of activated
      charcoal.

PMID- 23857699
TI  - Screening for F508del as a first step in the molecular diagnosis of cystic
      fibrosis.
AB  - OBJECTIVE: To determine the relevance of screening for the F508del mutation of
      the cystic fibrosis transmembrane conductance regulator gene as a first step in
      the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with
      various clinical variables. METHODS: We evaluated 180 CF patients regarding the
      F508del mutation. The clinical data were obtained from the medical records of the
      patients and from interviews with their parents or legal guardians. RESULTS: Of
      the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0
      [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del
      homozygous (G2). All three groups showed associations with the clinical
      variables. Homozygosis was associated with younger patients, younger age at CF
      diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA),
      as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid
      PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were
      older; first experienced clinical symptoms, digestive disease, and pulmonary
      disease at an older age; were older at CF diagnosis and at first PA isolation;
      and had a lower prevalence of PI and meconium ileus, as well as of colonization
      by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were
      intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary
      symptoms, and first clinical manifestations; MPA colonization; and OR for PI.
      CONCLUSIONS: The identification of F508del in 63.9% of the patients studied
      showed that this can be a useful tool as a first step in the genetic diagnosis of
      CF. The F508del genotype was associated with clinical severity of the disease,
      especially with the variables related to CF onset.

PMID- 23857700
TI  - Lung cysts in chronic paracoccidioidomycosis.
AB  - On HRCT scans, lung cysts are characterized by rounded areas of low attenuation
      in the lung parenchyma and a well-defined interface with the normal adjacent
      lung. The most common cystic lung diseases are lymphangioleiomyomatosis,
      Langerhans cell histiocytosis, and lymphocytic interstitial pneumonia. In a
      retrospective analysis of the HRCT findings in 50 patients diagnosed with chronic
      paracoccidioidomycosis, we found lung cysts in 5 cases (10%), indicating that
      patients with paracoccidioidomycosis can present with lung cysts on HRCT scans.
      Therefore, paracoccidioidomycosis should be included in the differential
      diagnosis of cystic lung diseases. 

PMID- 23857701
TI  - Importance of slow vital capacity in the detection of airway obstruction.
AB  - OBJECTIVE: To investigate the presence of airway obstruction by determining the
      FEV1/FVC and FEV1/slow vital capacity (SVC) ratios. METHODS: This was a
      quantitative, retrospective cross-sectional study. The sample comprised 1,084
      individuals who underwent spirometry and plethysmography in a central hospital in
      Lisbon, Portugal. The study sample was stratified into six groups, by pulmonary
      function. RESULTS: The analysis of the FEV1/FVC ratio revealed the presence of
      airway obstruction in 476 individuals (43.9%), compared with 566 individuals
      (52.2%) for the analysis of the FEV1/SVC ratio. In the airway obstruction, airway
      obstruction plus lung hyperinflation, and mixed pattern groups, the difference
      between SVC and FVC (SVC - FVC) was statistically superior to that in the normal
      pulmonary function, reduced FEF, and restrictive lung disease groups. The SVC -
      FVC parameter showed a significant negative correlation with FEV1 (in % of the
      predicted value) only in the airway obstruction plus lung hyperinflation group.
      CONCLUSIONS: The FEV1/SVC ratio detected the presence of airway obstruction in
      more individuals than did the FEV1/FVC ratio; that is, the FEV1/SVC ratio is more
      reliable than is the FEV1/FVC ratio in the detection of obstructive pulmonary
      disease.

PMID- 23857702
TI  - Ta3N5 nanowire bundles as visible-light-responsive photoanodes.

PMID- 23857703
TI  - Phosphatidylinositol-3,5-bisphosphate: metabolism and physiological functions.
AB  - Phosphatidylinositol (PtdIns) is a membrane phospholipid composed of
      diacylglycerol and a D-myo-inositol head group. In mammals, the hydroxyl groups
      at the D3, D4 and D5 positions of the inositol ring can be phosphorylated to
      yield seven phosphoinositide derivatives. PtdIns-3,5-bisphosphate [PtdIns(3,5)P2]
      is the most recently discovered species of phosphoinositide that is generated by
      the phosphorylation of PtdIns(3)P at the D5 position by PtdIns phosphate kinase
      and catabolized through the dephosphorylation by myotubularin family of
      phosphatases. Genetic and biochemical analyses of the enzymes metabolizing
      PtdIns(3,5)P2 have revealed that this phospholipid is involved in the control of
      endolysosomal systems and plays crucial roles in various mammalian tissues. In
      this article, we review the current state of knowledge of the
      metabolic/physiological functions of PtdIns(3,5)P2, and describe how disruption
      of these functions may contribute to human diseases.

PMID- 23857704
TI  - Tumour diploidy and survival in breast cancer patients with BRCA2 mutations.
AB  - It is not well known to what extent carrying a BRCA2 mutation affects the
      survival of women with breast cancer and prognostic factors among BRCA2-positive
      women warrant investigation. Using a record linkage approach we compared the long
      term survival in carriers and noncarriers of an inherited BRCA2 founder mutation
      (999del5), and sought to identify prognostic factors among the BRCA2 mutation
      positive subset, including markers of genetic instability (aneuploidy) and
      mitotic activity (S-phase fraction). We established the genetic status of 2,967
      Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers)
      diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the
      country during this period. Tumour ploidy and S-phase fraction were assessed on
      tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with
      respect to mutation status. Univariate and multivariate hazard ratios (HR) were
      estimated for breast cancer-specific survival by BRCA2 status, using Cox
      regression. After a median follow-up of 9.5 years, BRCA2 mutation carriers had a
      higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24
      2.16, p < 0.001). The risk increase was restricted to women with diploid tumours
      (HR 3.03, 95 % CI 1.91-4.79, p < 0.001). Among breast cancer patients with
      aneuploid tumours, survival of carriers was similar to that of noncarriers (HR
      0.76, 95 % CI 0.41-1.41, p = 0.38). Increased tumour size and a positive nodal
      status predicted worse prognosis in all patients, whereas the highly correlated
      prognostic factors diploidy, low proliferative activity and a positive estrogen
      receptor status had reverse effects in mutation carriers and noncarriers. Breast
      cancer patients who carry the Icelandic founder BRCA2 mutation have inferior long
      term survival than noncarriers, but the adverse prognosis is restricted to
      mutation carriers with diploid, slowly proliferating tumours. 

PMID- 23857705
TI  - Impact of attention deficit hyperactivity disorder-like symptoms on the clinical
      features of adolescents with pervasive developmental disorders.
AB  - INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD)-like symptoms are
      common among children and adolescents with Pervasive Developmental Disorders
      (PDD). The purpose of this study was to assess the impact of ADHD-like symptoms
      on the clinical features of adolescents with PDD. METHODS: A total of 72 subjects
      (between the ages of 12 and 17) diagnosed as having PDD were split into higher
      (ADHD+) and lower (ADHD-) groups according to the presence of ADHD-like symptoms
      as assessed with the Japanese version of the ADHD Rating Scale-IV (ADHD-RS-IV-J).
      Group differences in coexisting psychopathology, as assessed by the eight
      subscales of the Japanese version of the Child Behavior Checklist for Ages 4-18
      (CBCL/4-18-J) and autistic core features, as assessed by the adolescent part of
      the PDD-Autism Society of Japan Rating Scale (PARS), were examined. RESULTS: The
      ADHD + subjects showed a significantly higher degree of general psychopathology,
      including both externalizing and internalizing symptoms, as compared to subjects
      in the ADHD- subgroup. Additionally, the ADHD + subgroup showed greater
      impairment according to PARS scores. DISCUSSION: These results indicate an
      important role of ADHD-like symptoms in PDD. Therefore, parents/caregivers may
      find it useful to know to what extent their child's ADHD-like symptoms deviate
      from the norm for PDD adolescents and the implications of these symptoms for long
      term care. In addition, clinicians would be well advised to consider further
      systematic assessment of ADHD-like symptoms.

PMID- 23857706
TI  - Biomarker-based adaptive trials for patients with glioblastoma--lessons from I
      SPY 2.
AB  - The traditional clinical trials infrastructure may not be ideally suited to
      evaluate the numerous therapeutic hypotheses that result from the increasing
      number of available targeted agents combined with the various methodologies to
      molecularly subclassify patients with glioblastoma. Additionally, results from
      smaller screening studies are rarely translated to successful larger confirmatory
      studies, potentially related to a lack of efficient control arms or the use of
      unvalidated surrogate endpoints. Streamlining clinical trials and providing a
      flexible infrastructure for biomarker development is clearly needed for patients
      with glioblastoma. The experience developing and implementing the I-SPY studies
      in breast cancer may serve as a guide to developing such trials in neuro
      oncology. 

PMID- 23857708
TI  - Personality characteristics and body image in obese individuals.
AB  - INTRODUCTION: The aim of this study was to determine the personality
      characteristics of obese and morbidly obese individuals with no psychiatric
      disorder and the correlation between these characteristics and body image and
      self-esteem. METHODS: Sixty-nine obese individuals and 69 healthy controls,
      matched in age, sex and marital status, were included in the study. Psychiatric
      disorders were excluded for all participants using SCID-I and II. Obese and
      healthy volunteers were compared in terms of body image, self-esteem and
      personality characteristics. RESULTS: TCI harm avoidance scores were higher in
      obese individuals compared to healthy controls. Harm avoidance scores were also
      higher in individuals with morbid obesity compared to non-morbid individuals,
      while self-directedness and persistence scores were lower. Body image
      dissatisfaction was higher in obese individuals. There was a negative correlation
      in obese individuals between body image and self-esteem scale scores and harm
      avoidance scores, and a positive correlation with self-directedness scores.
      DISCUSSION: An elevated harm avoidance temperament characteristic may be
      correlated with obesity. Furthermore, high harm avoidance, low self-directedness
      and low persistence may be significant personality characteristics in a process
      leading to morbid obesity. In addition, harm avoidance temperament and self
      directedness personality characteristics may be correlated with body image
      dissatisfaction and self-esteem in obese individuals.

PMID- 23857707
TI  - Phase II study of irinotecan in combination with temozolomide (TEMIRI) in
      children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE
      brain tumor study.
AB  - BACKGROUND: This multicenter phase II study investigated temozolomide +
      irinotecan (TEMIRI) treatment in children with relapsed or refractory
      medulloblastoma. METHODS: Patients received temozolomide 100-125 mg/m(2)/day
      (days 1-5) and irinotecan 10 mg/m(2)/day (days 1-5 and 8-12) every 3 weeks. The
      primary endpoint was tumor response within the first 4 cycles confirmed >=4 weeks
      and assessed by an external response review committee (ERRC). In a 2-stage
      Optimum Simon design, >=6 responses in the first 15 evaluable patients were
      required within the first 4 cycles for continued enrollment; a total of 19
      responses from the first 46 evaluable patients was considered successful.
      RESULTS: Sixty-six patients were treated. Seven responses were recorded during
      stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and
      13 partial responses). The objective response rate during the first 4 cycles was
      32.6% (95% confidence interval [CI], 19.5%-48.0%). Median duration of response
      was 27.0 weeks (7.7-44.1 wk). In 63 patients evaluated by local investigators,
      the objective response rate was 33.3% (95% CI, 22.0%-46.3%), and 68.3% (95% CI,
      55.3%-79.4%) experienced clinical benefit. Median survival was 16.7 months (95%
      CI, 13.3-19.8). The most common grade 3 treatment-related nonhematologic adverse
      event was diarrhea (7.6%). Grade 3/4 treatment-related hematologic adverse events
      included neutropenia (16.7%), thrombocytopenia (12.1%), anemia (9.1%), and
      lymphopenia (9%). CONCLUSIONS: The planned study primary endpoint was not met.
      However, its tolerability makes TEMIRI a suitable candidate chemotherapy backbone
      for molecularly targeted agents in future trials in this setting.

PMID- 23857709
TI  - Voltage-impulse-induced non-volatile ferroelastic switching of ferromagnetic
      resonance for reconfigurable magnetoelectric microwave devices.
AB  - A critical challenge in realizing magnetoelectrics based on reconfigurable
      microwave devices, which is the ability to switch between distinct ferromagnetic
      resonances (FMR) in a stable, reversible and energy efficient manner, has been
      addressed. In particular, a voltage-impulse-induced two-step ferroelastic
      switching pathway can be used to in situ manipulate the magnetic anisotropy and
      enable non-volatile FMR tuning in FeCoB/PMN-PT (011) multiferroic
      heterostructures. 

PMID- 23857710
TI  - T1 measurements in the human myocardium: the effects of magnetization transfer on
      the SASHA and MOLLI sequences.
AB  - PURPOSE: Quantitative mapping of the native T1 of the heart using the modified
      look-locker inversion recovery (MOLLI) technique provides high quality diagnostic
      information without requiring contrast agents. Previous work has considered the
      effects of T2 relaxation on MOLLI T1 measurements, finding that the T1 measured
      by MOLLI is biased, and that Saturation-recovery single-Shot Acquisition
      generates a more precise T1. However, despite detailed experiments and simulation
      the exact relaxation times observed in vivo remain unexplained, but might be due
      to magnetization transfer (MT). METHODS: We used an MT simulation based on the
      Bloch-McConnell equations to evaluate the most common MOLLI and saturation
      recovery single-shot acquisition sequence variants. RESULTS: For myocardial
      tissue we find that the T1 measured by saturation-recovery single-shot
      acquisition is insensitive to MT and T2, whereas MT reduces the T1 measured by
      MOLLI (>10%) in addition to the effects due to T2 relaxation. CONCLUSIONS: The
      consequences of this T1 underestimation by MOLLI are relevant. Increases in the
      actual T1 and T2 and decreases in MT will all result in an increase in T1
      measured by MOLLI. Myocardial infarction demonstrates increased native T1 and T2
      and decreased MT, indicating that these biases enhance the sensitivity of MOLLI
      to detect this and possibly other cardiovascular disease states.

PMID- 23857711
TI  - The role of impedance monitoring in patients with extraesophageal symptoms.
AB  - OBJECTIVES/HYPOTHESIS: Ambulatory esophageal impedance monitoring is commonly
      employed to assess for nonacid reflux in patients with extraesophageal reflux. We
      aimed to determine if on therapy impedance data can be predicted from off therapy
      upper endoscopy, manometry, or pH parameters. STUDY DESIGN: Prospective Cohort
      Study. METHODS: Patients with extraesophageal reflux symptoms and either partial-
      or nonresponders to twice-daily PPI underwent impedance monitoring on twice-daily
      PPI, as well as manometry, upper endoscopy, and 48-hour wireless pH monitoring
      off acid-suppressive medications for 1 week. Percent time pH < 4 and number of
      reflux episodes were obtained. Multivariable linear regression was used to
      determine association between the impedance data on therapy and upper endoscopy,
      manometry, and pH parameters measured off therapy. RESULTS: Seventy-five patients
      (77% female, median BMI 29, 38% with hiatal hernia, and 19% with esophagitis)
      were studied both on and off therapy. Thirty-five percent had abnormal impedance
      monitoring on therapy and 84% had abnormal pH testing off therapy. There was no
      significant (P = 0.184) overall correlation between total number of impedance
      events and the baseline physiologic parameters of hiatal hernia, degree of acid
      reflux, or manometric findings, with only weak correlation (r = 0.54, P = 0.045)
      with % time pH < 4 among patients with esophagitis. CONCLUSIONS: In patients with
      suspected extraesophageal reflux refractory to PPI therapy, impedance measures on
      therapy cannot be predicted from traditional baseline esophageal physiologic
      parameters. We recommend caution regarding over-interpretation of impedance data.
      LEVEL OF EVIDENCE: 2b.

PMID- 23857712
TI  - Use of antidepressants in the treatment of depression in Asia: guidelines,
      clinical evidence, and experience revisited.
AB  - Major depressive disorder is prevalent worldwide, and only about half of those
      affected will experience no further episodes or symptoms. Additionally,
      depressive symptoms can be challenging to identify, with many patients going
      undiagnosed despite a wide variety of available treatment options.
      Antidepressants are the cornerstone of depression treatment; however, a large
      number of factors must be considered in selecting the treatment best suited to
      the individual. To help support physicians in this process, international and
      national treatment guidelines have been developed. This review evaluates the
      current use of antidepressant treatment for major depressive disorder in six
      Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No
      remarkable differences were noted between Asian and international treatment
      guidelines or among those from within Asia as these are adapted from western
      guidelines, although there were some local variations. Importantly, a shortage of
      evidence-based information at a country level is the primary problem in
      developing guidelines appropriate for Asia, so most of the guidelines are
      consensus opinions derived from western research data utilized in western
      guidelines. Treatment guidelines need to evolve from being consensus based to
      evidence based when evidence is available, taking into consideration
      cost/effectiveness or cost/benefit with an evidence-based approach that more
      accurately reflects clinical experience as well as the attributes of each
      antidepressant. In everyday practice, physicians must tailor their treatment to
      the patient's clinical needs while considering associated external factors;
      better tools are needed to help them reach the best possible prescribing
      decisions which are of maximum benefit to patients. 

PMID- 23857714
TI  - Enantiomeric separation of proton pump inhibitors on new generation chiral
      columns using LC and supercritical fluid chromatography.
AB  - The enantioselectivity of proton pump inhibitors, namely, omeprazole,
      lansoprazole, rabeprazole, pantoprazole, tenatoprazole, and ilaprazole were
      studied using new generation chiral packing materials: CHIRALPAK IA, CHIRALPAK
      IB, and CHIRALPAK IC. Two versatile techniques, HPLC and supercritical fluid
      chromatography (SFC) were used in this study. CHIRALPAK IC has shown superior
      selectivity under both LC and SFC conditions, whereas CHIRALPAK IA has shown good
      selectivity in SFC when compared to LC under primary screening conditions. The
      chiral recognition ability in LC and SFC modes were found to be in the order
      CHIRALPAK IC > CHIRALPAK IA > CHIRALPAK IB. In addition to diode array detection,
      chiral detection was carried out using a laser polarimeter and the elution orders
      were found to be the same in both LC and SFC elution modes. Mobile phase
      modifiers and column temperature effects were also studied. In SFC, modifiers
      (cosolvent) elution strength was found to be in the order ethanol > methanol > 2
      propanol > acetonitrile. In both LC and SFC, a decrease in retention and increase
      in resolution with an increase in temperature was noticed for all the proton pump
      inhibitors. 

PMID- 23857713
TI  - The U5 snRNA internal loop 1 is a platform for Brr2, Snu114 and Prp8 protein
      binding during U5 snRNP assembly.
AB  - The U5 small nuclear ribonucleoprotein particle (snRNP) forms the heart of the
      spliceosome which is required for intron removal from pre-mRNA. The proteins
      Prp8, Snu114 and Brr2 all assemble with the U5 small nuclear RNA (snRNA) to
      produce the U5 snRNP. Successful assembly of the U5 snRNP, then incorporation of
      this snRNP into the U4/U6.U5 tri-snRNP and the spliceosome, is essential for
      producing an active spliceosome. We have investigated the requirements for Prp8,
      Snu114 and Brr2 association with the U5 snRNA to form the U5 snRNP in yeast.
      Mutations were constructed in the highly conserved loop 1 and internal loop 1
      (IL1) of the U5 snRNA and their function assessed in vivo. The influence of these
      U5 mutations on association of Prp8, Snu114 and Brr2 with the U5 snRNA were then
      determined. U5 snRNA loop 1 and both sides of IL1 in U5 were important for
      association of Prp8, Snu114 and Brr2 with the U5 snRNA. Mutations in the 3' side
      of U5 IL1 resulted in the greatest reduction of Prp8, Snu114 and Brr2 association
      with the U5 snRNA. Genetic screening of brr2 and U5 snRNA mutants revealed
      synthetic lethal interactions between alleles in Brr2 and the 3' side of U5 snRNA
      IL1 which reflects reduced association between Brr2 and U5 IL1. We propose that
      the U5 snRNA IL1 is a platform for protein binding and is required for Prp8, Brr2
      and Snu114 association with the U5 snRNA to form the U5 snRNP.

PMID- 23857715
TI  - Direct writing of conducting polymers.
AB  - Described herein is a new printing method-direct writing of conducting polymers
      (CPs)-based on pipette-tip localized continuous electrochemical growth. A single
      barrel micropipette containing a metal wire (Pt) is filled with a mixture of
      monomer, supporting electrolyte, and an appropriate solvent. A droplet at the tip
      of the pipette contacts the substrate, which becomes the working electrode of a
      micro-electrochemical cell confined to the tip droplet and the pipette. The
      metallic wire in the pipette acts as both counter and reference electrode.
      Electropolymerization forms the CP on the working electrode in a pattern
      controlled by the movement of the pipette. In this study, various width
      poly(pyrrole) 2D and 3D structures are extruded and characterized in terms of
      microcyclic voltammetry, Raman spectroscopy, and scanning electron microscopy. 

PMID- 23857716
TI  - Emotion socialization style in parents of children with callous-unemotional
      traits.
AB  - Children with callous-unemotional (CU) traits manifest a range of deficits in
      their emotional functioning, and parents play a key role in socializing
      children's understanding, experience, expression, and regulation of emotions.
      However, research examining emotion-related parenting in families of children
      with CU traits is scarce. In two independent studies we examined emotion
      socialization styles in parents of children high on CU traits. In Study 1, we
      assessed parents' self-reported beliefs and feelings regarding their own and
      their child's emotions, in a sample of 111 clinic-referred and community children
      aged 7-12 years. In Study 2, we directly observed parents' responding to child
      emotion during an emotional reminiscing task, in a clinic sample of 59 conduct
      problem children aged 3-9 years. Taken together, the results were consistent in
      suggesting that the mothers of children with higher levels of CU traits are more
      likely to have affective attitudes that are less accepting of emotion (Study 1),
      and emotion socialization practices that are more dismissing of child emotion
      (Study 2). Fathers' emotion socialization beliefs and practices were unrelated to
      levels of CU traits. Our findings provide initial evidence for a relationship
      between CU traits and parents' emotion socialization style, and have significant
      implications for the design of novel family-based interventions targeting CU
      traits and co-occurring conduct problems.

PMID- 23857718
TI  - Mortality and morbidity hazards associated with cognitive status in seniors: a
      Canadian population prospective cohort study.
AB  - INTRODUCTION: Although cognitive impairment is widely accepted as a leading
      indicator of dementia, influences of cognitive status on incident dementia and
      mortality remain unclear. The present study investigated the morbidity hazard
      associated with cognitive impairment and the mortality hazard associated with
      dementia in comparison to cognitively intact seniors. METHODS: A population-based
      sample of 2914 seniors with clinically diagnosed cognitive status at Wave I (1991
      1992) of the Canadian Study of Health and Aging (CSHA) were followed-up 5 years
      later (1996-1997). At Wave I, there were 921 cognitively intact, 861 cognitively
      impaired but not demented (CIND), and 1132 seniors with dementia, respectively.
      The primary outcome measures 5 years later were being cognitively intact, CIND,
      dementia and death. Kaplan-Meier estimates, log-rank tests, and Cox's
      proportional models were used in the analyses. RESULTS: Respondents with CIND at
      Wave I were 2.191 times (95%CI 1.706-2.814) more likely to have dementia 5 years
      later than cognitively intact seniors. After adjusting for confounding socio
      demographic and health status factors, the odds ratio was reduced to 2.147 times
      (95%CI 1.662-2.774), but remained significant. Respondents with CIND had a
      mortality rate 1.869 times (95%CI 1.602-2.179) and seniors with dementia 3.362
      times greater (95%CI 2.929-3.860) than that of seniors who were cognitively
      intact. After controlling the confounders, the odds remained significant at 1.576
      (95%CI 1.348-1.843) for CIND respondents and 2.415 (95%CI 2.083-2.800) for
      seniors with dementia. DISCUSSION: CIND increases both the risk of dementia and
      mortality. Early intervention with CIND is warranted to reduce both dementia
      incidence and mortality.

PMID- 23857717
TI  - Airway basal cells of healthy smokers express an embryonic stem cell signature
      relevant to lung cancer.
AB  - Activation of the human embryonic stem cell (hESC) signature genes has been
      observed in various epithelial cancers. In this study, we found that the hESC
      signature is selectively induced in the airway basal stem/progenitor cell
      population of healthy smokers (BC-S), with a pattern similar to that activated in
      all major types of human lung cancer. We further identified a subset of 6 BC-S
      hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was
      associated with reduced lung function, poorer differentiation grade, more
      advanced tumor stage, remarkably shorter survival, and higher frequency of TP53
      mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a
      common TP53 inactivation molecular pattern which strongly correlated with the BC
      S hESC gene expression. These data provide transcriptome-based evidence that
      smoking-induced reprogramming of airway BC toward the hESC-like phenotype might
      represent a common early molecular event in the development of aggressive lung
      carcinomas in humans.

PMID- 23857720
TI  - Postsecondary education: kindling opportunities for people with mental illness.
AB  - Education is recognized in many sectors of society as essential for empowerment
      and better lives, and postsecondary education is increasingly a prerequisite for
      many occupations. Given its onset in late adolescence and early adulthood, mental
      illness frequently disrupts secondary or tertiary education, and resulting lower
      educational attainment contributes to reduced lifetime employment and earning
      potential. Yet, supporting people with mental illnesses to pursue postsecondary
      education offers pathways to vocational qualifications and more diverse
      opportunities for employment and career advancement. While substantial efforts
      have been made to develop evidence-based interventions to improve employment
      outcomes for people with mental ill health, less is known about the best ways to
      enable people with mental illness to successfully return to study and to pursue
      their educational goals. This paper briefly discusses supported education, an
      approach designed to provide pathways and supports for reengagement in education;
      it highlights the potential of modeling educational support on Individual
      Placement and Support principles used in supported employment programs; and calls
      for greater efforts in research and practice to enable youth or adults with
      mental illness to reengage in education so as to improve their educational
      outcomes and career prospects. 

PMID- 23857719
TI  - Total serum glycan analysis is superior to lectin-FLISA for the early detection
      of hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is a primary cancer of the liver that is
      predominantly the result of infection with a hepatotropic virus such as hepatitis
      B virus or hepatitis C virus. As liver cancer is often asymptomatic, the
      development of sensitive noninvasive biomarkers is needed for early detection and
      improved survival. EXPERIMENTAL DESIGN: We have previously identified alterations
      in the N-linked glycosylation of serum proteins with the development of HCC and
      identified many of the proteins that contained the altered glycosylation. In the
      current study, we compared the ability of the identified proteins to diagnose HCC
      with the total serum glycan analysis. RESULTS: Surprisingly, glycan analysis of
      total serum had the greatest ability to distinguish HCC from cirrhosis with an
      AUROC of 0.851, a sensitivity of 73% at a specificity of 88%. When total glycan
      sequencing was combined with alpha-fetoprotein (AFP), the sensitivity increased
      to 95% at a specificity of 90%. CONCLUSION AND CLINICAL RELEVANCE: Changes in
      glycosylation as detected in whole serum could be used to diagnose HCC with
      greater sensitivity and specificity than that observed through the analysis of
      specific protein glycoforms or protein levels. Such an assay could have value in
      the management of those at risk for the development of HCC.

PMID- 23857721
TI  - Effects of weight-bearing activities on bone mineral content and density in
      children and adolescents: a meta-analysis.
AB  - Osteoporosis and associated fractures are a major health concern in Western
      industrialized nations. Exercise during growth is suggested to oppose the
      involutional bone loss later in life by increasing peak bone mass. The primary
      aim of the present meta-analysis was to provide a robust estimate of the effect
      of weight-bearing activities (WBAs) on bone mineral content (BMC) and areal bone
      mineral density (aBMD), during childhood and adolescence. To locate relevant
      studies up to June 2012, computerized searches of multiple bibliographic
      databases and hand searches of key journals and reference lists were performed.
      Results were extracted by two independent reviewers. The quality of the included
      trials was assessed via the Physiotherapy Evidence Database (PEDro) score. The
      study group effect was defined as the difference between the standardized mean
      change for the treatment and control groups divided by the pooled pretest SD.
      From 109 potentially relevant studies, only 27 met the inclusion criteria. The
      analyzed training programs were capable of significantly increasing BMC and aBMD
      during growth. However, the weighted overall effect sizes (ESs) for changes in
      BMC (ES 0.17; 95% confidence interval [CI], 0.05-0.29; p < 0.05) and aBMD (ES
      0.26; 95% CI, 0.02-0.49) were small. Stepwise backward regression revealed that
      more than one-third of the observed variance (r(2)  = 0.35) between subgroups of
      the BMC dataset could be explained by differences in the amount of habitual
      calcium intake per day (beta 0.54, p < 0.01) and the maturational stage (beta 
      0.28, p < 0.01) at baseline. No significant moderators were identified for aBMD,
      possibly due to the small number of trials investigating WBAs on aBMD. The
      results of this meta-analysis conclude that WBAs alongside high calcium intake
      provide a practical, relevant method to significantly improve BMC in prepubertal
      children, justifying the application of this exercise form as an osteoporosis
      prophylaxis in this stage of maturity.

PMID- 23857722
TI  - Survey of premenstrual symptom severity and impairment in Korean adolescents:
      premenstrual dysphoric disorder, subthreshold premenstrual dysphoric disorder and
      premenstrual syndrome.
AB  - INTRODUCTION: The aims of the study were to examine the prevalence of
      premenstrual dysphoric disorder (PMDD), subthreshold PMDD and premenstrual
      syndrome (PMS) among adolescents, and to assess the nature of symptoms and the
      impact on daily life functions, especially for PMDD and subthreshold PMDD.
      METHODS: A cross-sectional survey was conducted among adolescents from an urban
      area. Participants included 984 girls divided into the following four groups,
      using a premenstrual symptoms screening tool: PMDD, subthreshold PMDD,
      moderate/severe PMS and no/mild PMS. An Adolescent Mental Problem Questionnaire,
      Center for Epidemiological Studies-Depression Scale, revised Children's Manifest
      Anxiety Scale, and a menstrual information questionnaire were also used. RESULTS:
      Sixty-three (6.76%) of the subjects met the criteria for PMDD and 58 (6.2%) were
      subthreshold PMDD. The subthreshold PMDD group included 79.3% who met the symptom
      criteria for PMDD, but their impairment was moderate, and 21.7% who were falling
      short by the number of symptoms for PMDD diagnosis, though reporting severe
      impairment. The symptom intensity and frequency of the subthreshold PMDD subjects
      were similar to those in subjects with PMDD. In these two groups, 69% had
      moderate to severe physical symptoms. Psychiatric problems, including depression
      and anxiety, were higher in the PMDD and subthreshold PMDD groups than in the
      moderate/severe PMS and no/mild PMS group. DISCUSSION: In total, 20% of
      adolescents reported suffering from distressing premenstrual symptoms, and girls
      with PMDD and subthreshold PMDD were very similar in their symptom severity and
      characteristics. Prospective daily charting is needed to confirm the accurate
      diagnosis and management of PMDD.

PMID- 23857724
TI  - Non-porous low-k dielectric films based on a new structural amorphous
      fluoropolymer.
AB  - A non-porous and amorphous fluoropolymer PFN with low dielectric constant of 2.33
      and dielectric loss less than 1.2 * 10(-3) is reported here. PFN also exhibits
      good mechanical properties and high thermostability. This study is a new example
      of a fully dense material showing a low k value and having good thermo/mechanical
      properties. 

PMID- 23857723
TI  - Acute liver failure caused by herpes simplex virus in a pregnant patient: is
      there a potential role for therapeutic plasma exchange?
AB  - A young woman presented with a febrile illness in the third trimester of
      pregnancy. Laboratory investigation revealed severe acute hepatitis with
      thrombocytopenia and coagulopathy. Liver injury progressed despite emergent
      caesarian section and delivery of a healthy infant. Therefore, therapeutic plasma
      exchange (TPE) was performed on three consecutive days post-partum for a presumed
      diagnosis of acute liver failure (ALF) associated with pregnancy due to
      hemolysis, elevated liver enzymes, and low platelets (HELLP) or acute fatty liver
      of pregnancy (AFLP). Treatment with TPE was followed by biochemical and clinical
      improvement but during her recovery herpes simplex virus type 2 (HSV-2) infection
      was diagnosed serologically and confirmed histologically. Changes in the immune
      system during pregnancy make pregnant patients more susceptible to acute HSV
      hepatitis, HSV-related ALF, and death. The disease is characterized by massive
      hepatic inflammation with hepatocyte necrosis, mediated by both direct viral
      cytotoxicity and the innate humoral immune response. TPE may have a therapeutic
      role in acute inflammatory disorders such as HSV hepatitis by reducing viral load
      and attenuating systemic inflammation and liver cell injury. Further
      investigation is needed to clarify this potential effect. The roles of vigilance,
      clinical suspicion, and currently accepted therapies are emphasized.

PMID- 23857725
TI  - Effect of electric field on the partitioning behavior of solutes in entropic
      interaction chromatography.
AB  - In this study, a novel column design with a round cross-section was proposed to
      be suitable for a transverse electric field (EF). Additionally, two beads for
      entropic interaction chromatography (EIC) were prepared by grafting glycidyl
      methacrylate onto Toyopearl HW-65F (T65F) beads. Solute partitioning was then
      investigated to elucidate the role of graft polymerization with and without an
      EF. In a T65F column, solute partitioning was attributed to the distinct pore
      structure in the beads and was governed by pore flow. Under EF, partition
      coefficients (Kp) for solutes decreased with increasing EF strength. In the two
      EIC columns, a decrease of Kp was also observed without an EF while the
      fractionation windows were extended. It was more pronounced in the EIC column
      with a high grafting density (T65F-H). This was explained by the decrease in the
      effective pore size of solutes caused by the steric hindrance of polymer chains.
      Under an EF, the solutes showed different partitioning behaviours in the T65F-H
      column. With increasing EF strength, Kp for vitamin B12 and myoglobin was
      decreased. In contrast, Kp for large solutes increased as a result of
      concentration polarization on the bead surface. Both behaviors were related to
      the modulation of graft polymerization to residual charge on the matrix and the
      pore size of the solutes.

PMID- 23857726
TI  - Responsive DNA-based hydrogels and their applications.
AB  - The term hydrogel describes a type of soft and wet material formed by cross
      linked hydrophilic polymers. The distinct feature of hydrogels is their ability
      to absorb a large amount of water and swell. The properties of a hydrogel are
      usually determined by the chemical properties of their constituent polymer(s).
      However, a group of hydrogels, called "smart hydrogels," changes properties in
      response to environmental changes or external stimuli. Recently, DNA or DNA
      inspired responsive hydrogels have attracted considerable attention in
      construction of smart hydrogels because of the intrinsic advantages of DNA. As a
      biological polymer, DNA is hydrophilic, biocompatible, and highly programmable by
      Watson-Crick base pairing. DNA can form a hydrogel by itself under certain
      conditions, and it can also be incorporated into synthetic polymers to form DNA
      hybrid hydrogels. Functional DNAs, such as aptamers and DNAzymes, provide
      additional molecular recognition capabilities and versatility. In this Review,
      DNA-based hydrogels are discussed in terms of their stimulus response, as well as
      their applications. 

PMID- 23857727
TI  - Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of
      neuropathic pain.
AB  - BACKGROUND: The function of brain networks can be changed in a maladaptive manner
      in response to chronic neuropathic pain. Analgesics can reduce pain by acting on
      such networks via direct or indirect (peripheral or spinal) mechanisms. This
      investigation aimed to map gabapentin's pharmacodynamics (PD) in the rodent brain
      following induction of neuropathic pain in order to further understand its PD
      profile. METHODS: Pharmacological magnetic resonance imaging (phMRI) and a novel
      functional connectivity analysis procedure were performed following vehicle or
      gabapentin treatment in the rat spinal nerve ligation (SNL) model of neuropathic
      pain as well as sham animals. RESULTS: phMRI performed in SNL animals revealed
      robust gabapentin-induced responses throughout the hippocampal formation, yet
      significant (p < 0.05, corrected for multiple comparisons) responses were also
      measured in other limbic structures and the sensorimotor system. In comparison,
      sham animals displayed weaker and less widespread phMRI signal changes subsequent
      to gabapentin treatment. Next, communities of networks possessing strong
      functional connectivity were elucidated in vehicle-treated SNL and sham animals.
      We observed that SNL and sham animals possessed distinct functional connectivity
      signatures. When measuring how gabapentin altered the behaviour of the discovered
      networks, a decrease in functional connectivity driven by gabapentin was not only
      observed, but the magnitude of this PD effect was greater in SNL animals.
      CONCLUSIONS: Using phMRI and functional connectivity analysis approaches, the PD
      effects of gabapentin in a preclinical neuropathic pain state were characterized.
      Furthermore, the current results offer insights on which brain systems gabapentin
      directly or indirectly acts upon.

PMID- 23857729
TI  - Factors influencing weight gain in an Asian population of psychiatric inpatients:
      a retrospective study in Taiwan.
AB  - INTRODUCTION: The aim of this study was to investigate the factors associated
      with weight gain by psychiatric inpatients in short-term treatment. METHODS: A
      total of 378 medical records were reviewed, and sociodemographic, clinical, and
      baseline biochemical data from 221 psychiatric inpatients were analyzed. RESULTS:
      Evaluation of baseline characteristics indicated that the following were
      significant predictors of weight gain: Axis I diagnosis, treatment with second
      generation antipsychotics and mood stabilizers, length of stay, admission body
      weight, low-density lipoprotein value, triglyceride level, and triglyceride/high
      density lipoprotein ratio. Multiple linear regression analysis showed that the
      independent predictors of weight gain were length of stay and taking both a
      second-generation antipsychotic and a mood stabilizer. The triglyceride/high
      density lipoprotein ratio was an influencing factor inversely associated with
      weight gain (P = 0.063). DISCUSSION: Length of hospitalization and polypharmacy
      strongly predicted weight gain among psychiatric inpatients receiving short-term
      treatment.

PMID- 23857730
TI  - Room temperature electrical and thermal switching CNT/hexadecane composites.
AB  - A large contrast in the electrical and thermal conductivities via a first order
      phase transition in surface-functionalized carbon nanotube(CNT)/hexadecane
      composites is reported. Surface modification of the CNTs improves the electrical
      conductivity contrast and the stability of the composites. We demonstrate that,
      with these composites, the electrical conductivity changes above 10(5) times and
      the thermal conductivity varies up to 3 times at 18  degrees C. 

PMID- 23857731
TI  - Association between religiosity/spirituality and quality of life or depression
      among living-alone elderly in a South Korean city.
AB  - INTRODUCTION: This study investigated the effects of religiosity and spirituality
      on quality of life and depression among older people. METHODS: Two hundred and
      seventy-four solitary elderly people aged over 65 years living in Chuncheon city,
      South Korea were selected. Symptoms of depression were evaluated using the Short
      Geriatric Depression Scale-Korean version (SGDS-K) and quality of life was
      measured using Geriatric Quality of Life-Dementia (GQOL-D). We used the Duke
      Religion Index (DUREL) to assess religiosity and spirituality. RESULTS: There was
      a significant correlation between scales of depression (SGDS-K), quality of life
      (GQOL-D), and scale of religiosity/spirituality (DUREL) in older people.
      Depressed people had a lower score GQOL-D than non-depressed people. Among the
      depressed, those believing in a religion had a higher GQOL-D score than the non
      religious. Multiple regression analysis revealed that religiosity and
      spirituality had significant effects on depression and quality of life among the
      elderly. Interestingly, religiosity and spirituality were not related to
      depression and quality of life amongst Buddhists, but were related amongst
      Protestants and Catholics. DISCUSSION: Religiosity and spirituality had
      significant effects on depression and on quality of life among the Korean
      elderly. However, there are different relationships between depression and
      religiosity, quality of life, and religiosity based on different religions. More
      research is needed to elucidate these findings.

PMID- 23857732
TI  - Cognitive behavioral intervention in the Chinese cultural context: a case report.
AB  - INTRODUCTION: Depression is predicted to become the world's second leading cause
      of disability by 2020 according to the World Health Organization. Cognitive
      behavioral intervention (CBI), recognized as a viable and effective treatment for
      depression, is becoming more widely used among Chinese clients. However,
      information about the application of this Western approach in the Chinese
      population is very limited. METHODS: This paper discusses adaptations of CBI
      protocols for Chinese patients, considering the major Chinese cultural
      characteristics of predestination, losing face, avoiding conflict, and Yin-Yang
      balance (PLAY) for persons with depression. RESULTS: Illustrated is the
      application of the PLAY protocol in the actual case of a 35-year-old woman with
      depression. Implications for integrating Chinese cultural characteristics with
      CBI are discussed. DISCUSSION: There is evidence for adaptations of CBI for
      enhancing its effectiveness among Chinese people within their cultural context.
      Since there are limited studies on cultural-sensitive CBI for Chinese people, the
      conclusions drawn from this study are only preliminary. Further studies that
      verify the findings reported in this paper are necessary.

PMID- 23857733
TI  - Liquid chromatography of synthetic polymers under critical conditions of
      enthalpic interactions 4: sample recovery.
AB  - Reduced sample recovery is a frequent feature of LC of macromolecules under
      critical conditions of enthalpic interactions (LC CC). Several methods of
      assessment of LC CC sample recovery are compared. A novel approach is based on an
      online combination of the. The LC CC column with a noninteractive SEC column. It
      provides not only the amount but also the molar mass of the eluted/withheld
      polymer. The procedure was tested with poly(methyl methacrylate), bare silica gel
      column packings, and "critical eluent" tetrahydrofuran/toluene. It was shown that
      macromolecules with higher molar masses were preferentially trapped within the LC
      CC column packing so that the eluted part of the sample was no longer
      representative. The incomplete polymer elution can make the LC CC polymer
      analyses susceptible to significant experimental errors. 

PMID- 23857728
TI  - Tn and sialyl-Tn antigens, aberrant O-glycomics as human disease markers.
AB  - In many different human disorders, the cellular glycome is altered. An
      interesting but poorly understood alteration occurs in the mucin-type O-glycome,
      in which there is aberrant expression of the truncated O-glycans Tn (GalNAcalpha1
      Ser/Thr) and its sialylated version sialyl-Tn (STn) (Neu5Acalpha2,6GalNAcalpha1
      Ser/Thr). Both Tn and STn are tumor-associated carbohydrate antigens and tumor
      biomarkers, since they are not expressed normally and appear early in
      tumorigenesis. Moreover, their expression is strongly associated with poor
      prognosis and tumor metastasis. The Tn and STn antigens are also expressed in
      other human diseases and disorders, such as Tn syndrome and IgA nephropathy. The
      major pathological mechanism for expression of the Tn and STn antigens is
      compromised T-synthase activity, resulting from alteration of the X-linked gene
      that encodes for Cosmc, a molecular chaperone specifically required for the
      correct folding of T-synthase to form active enzyme. This review will summarize
      our current understanding of the Tn and STn antigens in terms of their
      biochemistry and role in pathology. 

PMID- 23857734
TI  - Facile one-step synthesis of monodisperse micron-sized latex particles with
      highly carboxylated surfaces.
AB  - A facile method for the aqueous synthesis of monodisperse and micronmeter-sized
      colloids with highly carboxylated surfaces is presented. The method is applied to
      three different monomers, styrene, methyl methacrylate, and 2,2,2-trifluoroethyl
      methacrylate, and illustrate tuning of the size and monodispersity in the
      reactions. High surface density of carboxylic acids of up to 10 COOH nm(-2) from
      potentiometric titrations, is achieved through copolymerization with itaconic
      acid. The versatility of this system is highlighted by creating highly
      fluorescent and monodisperse particles that can be index matched in aqueous
      solution and through surface modification via the carboxylic acid groups using
      standard amidation chemistry. 

PMID- 23857736
TI  - Genetic patterns of habitat fragmentation and past climate-change effects in the
      Mediterranean high-mountain plant Armeria caespitosa (Plumbaginaceae).
AB  - PREMISE OF THE STUDY: Mountain plants are among the species most vulnerable to
      global warming, because of their isolation, narrow geographic distribution, and
      limited geographic range shifts. Stochastic and selective processes can act on
      the genome, modulating genetic structure and diversity. Fragmentation and
      historical processes also have a great influence on current genetic patterns, but
      the spatial and temporal contexts of these processes are poorly known. We aimed
      to evaluate the microevolutionary processes that may have taken place in
      Mediterranean high-mountain plants in response to changing historical
      environmental conditions. METHODS: Genetic structure, diversity, and loci under
      selection were analyzed using AFLP markers in 17 populations distributed over the
      whole geographic range of Armeria caespitosa, an endemic plant that inhabits
      isolated mountains (Sierra de Guadarrama, Spain). Differences in altitude,
      geographic location, and climate conditions were considered in the analyses,
      because they may play an important role in selective and stochastic processes.
      KEY RESULTS: Bayesian clustering approaches identified nine genetic groups,
      although some discrepancies in assignment were found between alternative
      analyses. Spatially explicit analyses showed a weak relationship between genetic
      parameters and spatial or environmental distances. However, a large proportion of
      outlier loci were detected, and some outliers were related to environmental
      variables. CONCLUSIONS: A. caespitosa populations exhibit spatial patterns of
      genetic structure that cannot be explained by the isolation-by-distance model.
      Shifts along the altitude gradient in response to Pleistocene climatic
      oscillations and environmentally mediated selective forces might explain the
      resulting structure and genetic diversity values found.

PMID- 23857735
TI  - Gas exchange, growth, and defense responses of invasive Alliaria petiolata
      (Brassicaceae) and native Geum vernum (Rosaceae) to elevated atmospheric CO2 and
      warm spring temperatures.
AB  - PREMISE OF STUDY: Global increases in atmospheric CO2 and temperature may
      interact in complex ways to influence plant physiology and growth, particularly
      for species that grow in cool, early spring conditions in temperate forests.
      Plant species may also vary in their responses to environmental changes; fast
      growing invasives may be more responsive to rising CO2 than natives and may
      increase production of allelopathic compounds under these conditions, altering
      species' competitive interactions. METHODS: We examined growth and physiological
      responses of Alliaria petiolata, an allelopathic, invasive herb, and Geum vernum,
      a co-occurring native herb, to ambient and elevated spring temperatures and
      atmospheric CO2 conditions in a factorial growth chamber experiment. KEY RESULTS:
      At 5 wk, leaves were larger at high temperature, and shoot biomass increased
      under elevated CO2 only at high temperature in both species. As temperatures
      gradually warmed to simulate seasonal progression, G. vernum became responsive to
      CO2 at both temperatures, whereas A. petiolata continued to respond to elevated
      CO2 only at high temperature. Elevated CO2 increased thickness and decreased
      nitrogen concentrations in leaves of both species. Alliaria petiolata showed
      photosynthetic downregulation at elevated CO2, whereas G. vernum photosynthesis
      increased at elevated temperature. Flavonoid and cyanide concentrations decreased
      significantly in A. petiolata leaves in the elevated CO2 and temperature
      treatment. Total glucosinolate concentrations and trypsin inhibitor activities
      did not vary among treatments. CONCLUSIONS: Future elevated spring temperatures
      and CO2 will interact to stimulate growth for A. petiolata and G. vernum, but
      there may be reduced allelochemical effects in A. petiolata.

PMID- 23857737
TI  - Ecological factors influencing growth of the endangered Hawaiian fern Marsilea
      villosa (Marsileaceae) and implications for conservation management.
AB  - PREMISE OF THE STUDY: Conserving endangered plants is a complex task, and
      practitioners must often use a "triage" approach, addressing only immediate
      needs. Ecologists can improve this process by conducting sound science upon which
      to base management. Marsilea villosa is an endangered, endemic Hawaiian fern with
      seven remaining populations in ephemerally flooding drylands. Among its uncommon
      traits are long-lived sporocarps, requiring flood and drought to complete its
      sexual life cycle, and extensive vegetative growth. METHODS: We conducted a 3-yr
      ecological field study, measuring percent cover of M. villosa and associated
      species, flooding depth, and canopy cover, to identify ecological factors with
      the greatest impact on M. villosa growth. KEY RESULTS: Maximum flooding depth and
      canopy cover had strong positive relationships with M. villosa growth, and all
      plots with >50% threshold of either variable reached 100% cover of M. villosa by
      the end of the study. Interaction effects explained nuances of these
      relationships, including synergy between the two variables. Percent cover of
      nonnative functional groups (graminoids and nongraminoids) each had negative
      relationships with M. villosa growth, but interactions showed that nongraminoid
      cover was driven by particular species, and that time since flooding had greater
      influence on M. villosa growth than graminoid cover. CONCLUSIONS: We recommend
      planting reintroduced populations in flood-prone areas with moderate shade,
      experimental outplanting of native plants with M. villosa, and management of
      graminoids as a functional group, while nongraminoid management should be species
      specific. These practices will promote self-sustaining populations and reduce the
      need for labor-intensive management.

PMID- 23857738
TI  - Antegrade approach for TAVR with total occlusion of the descending aorta.
AB  - The antegrade approach for aortic valve interventions is well known but has not
      been widely used for transcatheter aortic valve replacement (TAVR) procedures. We
      encountered a patient with no possibility of retrograde access due to a totally
      occluded abdominal aorta who had a failed attempt at apical TAVR. We describe
      antegrade TAVR despite occlusion of the abdominal aorta, with the arterial limb
      of the requisite veno-arterial loop created using bilateral arm access, a novel
      version of the previously described antegrade approach.

PMID- 23857741
TI  - High-sensitivity CRP is an independent risk factor for all fractures and
      vertebral fractures in elderly men: the MrOS Sweden study.
AB  - Epidemiological studies have shown low-grade inflammation measured by high
      sensitivity C-reactive protein (hs-CRP) to be associated with fracture risk in
      women. However, it is still unclear whether hs-CRP is also associated with
      fracture risk in men. We therefore measured serum levels of hs-CRP in 2910 men,
      mean age 75 years, included in the prospective population-based MrOS Sweden
      cohort. Study participants were divided into tertile groups based on hs-CRP
      level. Fractures occurring after the baseline visit were validated (average
      follow-up 5.4 years). The incidence for having at least one fracture after
      baseline was 23.9 per 1000 person-years. In Cox proportional hazard regression
      analyses adjusted for age, hs-CRP was related to fracture risk. The hazard ratio
      (HR) of fracture for the highest tertile of hs-CRP, compared with the lowest and
      the medium tertiles combined, was 1.48 (95% CI, 1.20-1.82). Multivariate
      adjustment for other risk factors for fractures had no major effect on the
      associations between hs-CRP and fracture. Results were essentially unchanged
      after exclusion of subjects with hs-CRP levels greater than 7.5 mg/L, as well as
      after exclusion of subjects with a first fracture within 3 years of follow-up,
      supporting that the associations between hs-CRP and fracture risk were not merely
      a reflection of a poor health status at the time of serum sampling. Femoral neck
      bone mineral density (BMD) was not associated with hs-CRP, and the predictive
      role of hs-CRP for fracture risk was essentially unchanged when femoral neck BMD
      was added to the model (HR, 1.37; 95% CI, 1.09-1.72). Exploratory subanalyses of
      fracture type demonstrated that hs-CRP was clearly associated with clinical
      vertebral fractures (HR, 1.61; 95% CI, 1.12-2.29). We demonstrate, using a large
      prospective population-based study, that elderly men with high hs-CRP have
      increased risk of fractures, and that these fractures are mainly vertebral. The
      association between hs-CRP and fractures was independent of BMD. This is an open
      access article under the terms of the Creative Commons Attribution-NonCommercial
      NoDerivs License, which permits use and distribution in any medium, provided the
      original work is properly cited, the use is non-commercial and no modifications
      or adaptations are made.

PMID- 23857743
TI  - One-dimensional hierarchical nanostructures of TiO(2) nanosheets on SnO(2)
      nanotubes for high efficiency solid-state dye-sensitized solar cells.
AB  - Hierarchical nanostructures of TiO2 nanosheets on SnO2 nanotubes (SNT@TNS) are
      uniformly dispersed in an organized mesoporous (OM) TiO2 film with large pores,
      high porosity, and good interconnectivity. The solid-state dye sensitized solar
      cells (ssDSSCs) fabricated with 10 wt% SNT@TNS dispersed in a OM-TiO2 film show
      an energy conversion efficiency of 7.7% at 100 mW cm(-2) , which is one of the
      highest values for N719-based ssDSSCs and much larger than that of a randomly
      oriented TiO2 nanoparticles-based cell (4.0%). 

PMID- 23857742
TI  - Is it useful to use the Korean version of the mood disorder questionnaire for
      assessing bipolar spectrum disorder among Korean college students?
AB  - INTRODUCTION: The purpose of this study was to assess the usefulness of the
      Korean version of the Mood Disorder Questionnaire (K-MDQ) as a screening tool for
      the identification of bipolar spectrum disorder (BSD) among Korean college
      students. METHODS: The sample of 1,020 college students was stratified to reflect
      geographical differences among the students. The K-MDQ and an epidemiological
      survey were administered between November 2006 and February 2007. To validate the
      K-MDQ as a screening tool for BSD, the Korean version of the Bipolar Spectrum
      Diagnostic Scale (K-BSDS) and the Structured Clinical Interview for DSM-IV (SCID)
      were also administered. RESULTS: The rates satisfying MDQ criterion 1, and all
      three MDQ criteria, were 55.5% and 2.3%, respectively. According to the K-BSDS,
      59.9% of the sample met the criteria for BSD using a threshold of 10, while no
      statistical differences were observed among subgroups. When we examined the
      diagnostic agreement between K-MDQ and K-BSDS, 79.5% of students who met MDQ
      criterion 1 were also positive on the BSDS. Sixteen (21.6%) of the 74 students
      who participated in the SCID interview were diagnosed with BSD. DISCUSSION:
      Although the K-MDQ is a useful tool to assess BSD among inpatients and
      outpatients, it does not appear useful as a screening tool to detect BSD among
      college students.

PMID- 23857744
TI  - Soluble amyloid precursor protein 770 is a novel biomarker candidate for acute
      coronary syndrome.
AB  - Most Alzheimer disease patients show deposition of amyloid beta (Abeta) peptide
      in blood vessels as well as the brain parenchyma. We previously found that
      vascular endothelial cells express amyloid beta precursor protein (APP) 770, a
      different APP isoform from neuronal APP695, and that they produce amyloid beta
      peptide. We analyzed the glycosylation of APP770 and found that O-glycosylated
      sAPP770 is preferentially processed by proteases for Abeta production. Because
      the soluble APP cleavage product sAPP is considered to be a possible marker for
      Alzheimer disease diagnosis, sAPP, consisting of a mixture of these variants, has
      been widely measured. We hypothesized that measurement of the endothelial APP770
      cleavage product in patients separately from that of neuronal APP695 would enable
      us to discriminate between endothelial and neurological dysfunctions. Our recent
      findings, showing that the level of plasma sAPP770 is significantly higher in
      patients with acute coronary syndrome, raise the possibility that sAPP770 could
      be an indicator of endothelial dysfunction. In this review, we first describe the
      expression, glycosylation, and processing of APP770, and then discuss sAPP770 as
      a novel biomarker candidate of acute coronary syndrome. 

PMID- 23857745
TI  - Characteristics of bipolar symptoms in psychiatric patients: pattern of responses
      to the Korean version of the Mood Disorder Questionnaire.
AB  - INTRODUCTION: Bipolar disorders are relatively frequent but easily misdiagnosed.
      The Korean version of the Mood Disorder Questionnaire (K-MDQ) is a screening
      instrument for bipolar disorders. The aim of this study was to establish the
      pattern of responses to the K-MDQ for several psychiatric disorders. METHODS: The
      subjects for this study were 345 patients with bipolar disorders, schizophrenia,
      depressive disorders or anxiety disorders, as determined using the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and 96
      controls from five hospitals. The subjects completed the questionnaire by
      themselves. RESULTS: The total K-MDQ score was higher in the bipolar disorder
      group than the other groups. Although the mean K-MDQ score differed significantly
      between the bipolar disorder group and the other groups, the distributions of
      total scores for the groups overlapped, and in particular with the schizophrenia
      group. The area under the receiver operating characteristics curve was relatively
      high for the bipolar disorder group and the other subjects, but it was less than
      0.8 between the bipolar disorder group, and the schizophrenia and control groups.
      DISCUSSION: There are some distinguishing features of the K-MDQ pattern for each
      disorder, but their similarities were significant. This made it difficult to
      differentially diagnose the disorder using only the total K-MDQ score. The
      diagnostic power of the K-MDQ can only be improved in the clinical setting by
      utilizing reinforcing criteria to diagnose bipolar disorders. Clinicians should
      be cautious in their interpretation of the K-MDQ, and the use of additional data
      is essential.

PMID- 23857746
TI  - cDNA cloning, localization, and candidate binding partners of acid-extractable
      vitelline-coat protein Ci-v-Themis-like in the ascidian Ciona intestinalis.
AB  - Ascidians are hermaphrodites, although several ascidian species show self
      sterility because of the occurrence of a self/nonself-recognition system called
      the self-incompatibility system. We previously reported that two pairs of sperm
      polycystin 1-like receptors, s-Themis-A and s-Themis-B, and egg fibrinogen-like
      ligands, v-Themis-A and v-Themis-B, are responsible for self-incompatibility in
      the ascidian Ciona intestinalis. Our previous results showed that v-Themis-A and
      v-Themis-B were hardly extracted from the vitelline coat (VC) by acid treatment,
      which is not in accordance with a report that an acid-extractable VC factor has
      the ability to distinguish self- from nonself-sperm. These results led us to
      explore a novel factor from acid-extractable VC proteins that could be involved
      in self-incompatibility. Here, we report cDNA cloning, expression, and
      localization of Ci-v-Themis-like, a major acid-extractable VC protein. This
      protein has a fibrinogen-like domain, as do v-Themis-A and v-Themis-B, but it
      showed no polymorphisms. Phylogenic analysis suggested that Ci-v-Themis-like is
      an ancestral protein of v-Themis-A and v-Themis-B. Whole mount in situ
      hybridization revealed that Ci-v-Themis-like mRNA is expressed in the ovary and
      testis. Western blotting and immunocytochemistry showed the occurrence of Ci-v
      Themis-like in developing oocytes and on the VC of mature eggs. Yeast two-hybrid
      screenings using testis and ovary libraries revealed candidate interacting
      proteins; among these candidates, we succeeded in identifying several testis
      specific proteins, including sperm proteases and coiled-coil-domain-containing
      proteins. The results suggest that Ci-v-Themis-like and its binding partners are
      involved in sperm binding to the VC prior to the allorecognition process during
      C. intestinalis fertilization.

PMID- 23857748
TI  - Predictors of success at six-month follow-up at a public smoking cessation clinic
      in South Korea.
AB  - INTRODUCTION: Our objective was to identify the factors related to returning to
      smoking by analyzing data obtained from a smoking cessation clinic. METHODS: We
      analyzed data from 2,089 subjects (age 44.0 +/- 12.9 years) who started a smoking
      cessation program between 16 July 2007 and 31 December 2008 in a community health
      center in the city of Ulsan. We analyzed demographic information and clinical
      variables using Kaplan-Meier survival analysis and calculated the hazard ratio
      for returning to smoking. RESULTS: Mean abstinence time differed according to the
      following factors: sex, past attempts to quit, employment status, type of health
      insurance, CO levels, results from Fagerstrom test for nicotine dependence
      (FTND), number of cigarettes smoked daily, use of a nicotine replacement, and
      number of contacts in the program. Using multivariate analysis, we identified
      negative relationships between treatment intensity and hazard ratio for the
      following: visits <=4 (Exp(B) = 3.752, P < 0.001, reference: 5 visits <=),
      telephone contacts <=5 (Exp(B) = 10.528, P < 0.001, reference: 6 calls <=) and
      SMS <= 20 (Exp(B) = 3.821, P < 0.001 in 0-10 group; Exp(B) = 1.407, P = 0.003 for
      the 11-20 group; reference: 21 messages <=). DISCUSSION: Type of insurance,
      baseline CO, FTND level, and intensity of smoking cessation intervention
      positively affects outcomes in a smoking cessation clinic. A cost-effectiveness
      study on the intensity of interventions in smoking cessation clinics is needed.

PMID- 23857747
TI  - Delayed bone regeneration is linked to chronic inflammation in murine muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) patients exhibit skeletal muscle weakness with
      continuous cycles of muscle fiber degeneration/regeneration, chronic
      inflammation, low bone mineral density, and increased risks of fracture.
      Fragility fractures and associated complications are considered as a consequence
      of the osteoporotic condition in these patients. Here, we aimed to establish the
      relationship between muscular dystrophy and fracture healing by assessing bone
      regeneration in mdx mice, a model of DMD with absence of osteoporosis. Our
      results illustrate that muscle defects in mdx mice impact the process of bone
      regeneration at various levels. In mdx fracture calluses, both cartilage and bone
      deposition were delayed followed by a delay in cartilage and bone remodeling.
      Vascularization of mdx fracture calluses was also decreased during the early
      stages of repair. Dystrophic muscles are known to contain elevated numbers of
      macrophages contributing to muscle degeneration. Accordingly, we observed
      increased macrophage recruitment in the mdx fracture calluses and abnormal
      macrophage accumulation throughout the process of bone regeneration. These
      changes in the inflammatory environment subsequently had an impact on the
      recruitment of osteoclasts and the remodeling phase of repair. Further damage to
      the mdx muscles, using a novel model of muscle trauma, amplified both the chronic
      inflammatory response and the delay in bone regeneration. In addition, PLX3397
      treatment of mdx mice, a cFMS (colony stimulating factor receptor 1) inhibitor in
      monocytes, partially rescued the bone repair defect through increasing cartilage
      deposition and decreasing the number of macrophages. In conclusion, chronic
      inflammation in mdx mice contributes to the fracture healing delay and is
      associated with a decrease in angiogenesis and a transient delay in osteoclast
      recruitment. By revealing the role of dystrophic muscle in regulating the
      inflammatory response during bone repair, our results emphasize the implication
      of muscle in the normal bone repair process and may lead to improved treatment of
      fragility fractures in DMD patients.

PMID- 23857749
TI  - Negative effects of climate warming on maize yield are reversed by the changing
      of sowing date and cultivar selection in Northeast China.
AB  - Northeast China (NEC) accounts for about 30% of the nation's maize production in
      China. In the past three decades, maize yields in NEC have increased under
      changes in climate, cultivar selection and crop management. It is important to
      investigate the contribution of these changing factors to the historical yield
      increases to improve our understanding of how we can ensure increased yields in
      the future. In this study, we use phenology observations at six sites from 1981
      to 2007 to detect trends in sowing dates and length of maize growing period, and
      then combine these observations with in situ temperature data to determine the
      trends of thermal time in the maize growing period, as a measure of changes in
      maize cultivars. The area in the vicinity of these six sites accounts for 30% of
      NEC's total maize production. The agricultural production systems simulator,
      APSIM-Maize model, was used to separate the impacts of changes in climate, sowing
      dates and thermal time requirements on maize phenology and yields. In NEC, sowing
      dates trended earlier in four of six sites and maturity dates trended later by 4
      21 days. Therefore, the period from sowing to maturity ranged from 2 to 38 days
      longer in 2007 than it was in 1981. Our results indicate that climate trends
      alone would have led to a negative impact on maize. However, results from the
      adaptation assessments indicate that earlier sowing dates increased yields by up
      to 4%, and adoption of longer season cultivars caused a substantial increase in
      yield ranging from 13% to 38% over the past 27 years. Therefore, earlier sowing
      dates and introduction of cultivars with higher thermal time requirements in NEC
      have overcome the negative effects of climate change and turned what would have
      otherwise been a loss into a significant increase in maize yield. 

PMID- 23857750
TI  - Novel affinity purification of monomeric sarcosine oxidase expressed in
      Escherichia coli.
AB  - An efficient affinity-purification protocol for Bacillus monomeric sarcosine
      oxidase (SOX) expressed in Escherichia coli BL21 (DE3) was developed. 4
      Aminopyrrole-2-carboxylic acid was chosen as the affinity ligand, which was
      coupled with Sepharose CL 4B via spacers composed of epichlorohydrin and
      ethylenediamine. With the affinity medium, the purification process consisted of
      only one affinity chromatography step to capture monomeric SOX. The purified SOX
      was 94 and 96% pure when analyzed on an HPLC Vydac C8 column and reducing SDS
      PAGE. Meanwhile, the recoveries of typical SOX activity and protein were 90.8 and
      37.5%, respectively, which were higher than other reported traditional protocols.
      Reducing SDS-PAGE analysis revealed that the enzyme was a single polypeptide with
      the mass of ~46 kDa. The desorption constant Kd and theoretical maximum
      absorption Qmax were 35 MUg/mL and 52.7 mg/g, respectively, in absorption
      analysis. All results indicated that the method would be of great potential for
      purifying monomeric SOX on an industrial scale.

PMID- 23857751
TI  - Early experience of implantation of the new CoreValve((r)) Evolut(TM) in
      degenerated bioprosthetic aortic valves.
AB  - Transcatheter aortic valve implantation (TAVI) is an established treatment for
      severe aortic stenosis in high-risk patients. The PARTNER trial demonstrated
      equivalent 1-year survival rates between patients randomized to TAVI versus
      conventional surgery (Leon et al., N Engl J Med 2010;363:1597-1607), with
      sustained benefit up to 2 years (Makkar et al., NEJM 2012;366:1696-1704).
      Recently, the ADVANCE registry cited all-cause mortality rates of 4.5%, 12.8%,
      and 17.9% at 30-days, 6 months, and 1-year following TAVI in 1,015 high-risk
      patients (Linke, TCT 2012, 2012). In addition, TAVI was demonstrated to be a
      feasible treatment for severe native valve regurgitation in a series of 31 high
      risk patients. The all-cause 30-day mortality rate was 6.4%, with a 30-day major
      stroke rate of 6.4%. At 1-year, the all-cause mortality rate was 12.5% (Roy et
      al., J Am Coll Cardiol 2012;60(17S):B264). We report the successful transcatheter
      implantation of the new CoreValve((r)) Evolut(TM) in two patients with
      regurgitant aortic bioprostheses.

PMID- 23857752
TI  - Elastin haploinsufficiency impedes the progression of arterial calcification in
      MGP-deficient mice.
AB  - Matrix gla protein (MGP) is a potent inhibitor of extracellular matrix (ECM)
      mineralization. MGP-deficiency in humans leads to Keutel syndrome, a rare genetic
      disease hallmarked by abnormal soft tissue calcification. MGP-deficient (Mgp(-/
      )) mice show progressive deposition of hydroxyapatite minerals in the arterial
      walls and die within 2 months of age. The mechanism of antimineralization
      function of MGP is not fully understood. We examined the progression of vascular
      calcification and expression of several chondrogenic/osteogenic markers in the
      thoracic aortas of Mgp(-/-) mice at various ages. Although cells with chondrocyte
      like morphology have been reported in the calcified aorta, our gene expression
      data indicate that chondrogenic/osteogenic markers are not upregulated in the
      arteries prior to the initiation of calcification. Interestingly, arterial
      calcification in Mgp(-/-) mice appears first in the elastic laminae. Considering
      the known mineral scaffolding function of elastin (ELN), a major elastic lamina
      protein, we hypothesize that elastin content in the laminae is a critical
      determinant for arterial calcification in Mgp(-/-) mice. To investigate this, we
      performed micro-computed tomography (uCT) and histological analyses of the aortas
      of Mgp(-/-);Eln(+/-) mice and show that elastin haploinsufficiency significantly
      reduces arterial calcification in this strain. Our data suggest that MGP
      deficiency leads to alterations of vascular ECM that may in turn initiate
      arterial calcification.

PMID- 23857753
TI  - Australian consumer perceptions of peer support.
AB  - INTRODUCTION: Peer support in mental health service delivery is a relatively new
      development in Western Australia, occurring only in the last decade.
      Consequently, what is known about peer support in mental health has been largely
      drawn from the overseas literature. The purpose of the present study was to
      identify how consumers of mental health services in Western Australia viewed the
      impact that peer support workers had on their life. METHODS: The nominal group
      technique was the method used to collect and analyze the data from nine
      participants living in the community who were supported by a peer support worker;
      the role of the peer support worker was to encourage healthy lifestyle behaviors.
      RESULTS: The results indicate that the main influences of a peer worker for
      consumers were motivation, increased social interaction, living a healthier
      lifestyle, positive mental attitude and building confidence. DISCUSSION: It was
      concluded that participants viewed the support they received as a positive
      experience, which contributed to building confidence and enabled participants to
      make lifestyle changes. However, the results need to be viewed with caution, not
      only because of the small sample size, but also because the peer workers and the
      participants were all male. Results may well be different where the role and
      gender of the support worker and consumer are different.

PMID- 23857754
TI  - Family adaptability and cohesion in families consisting of Asian immigrant women
      living in South Korea: A 3-year longitudinal study.
AB  - INTRODUCTION: South Korea's low birth rate, aging society, and female migration
      to urban areas due to industrialization have caused an accelerated inflow of
      Asian female immigrants into Korea to marry Korean men, especially in rural
      areas. This study was performed to determine how family function of multicultural
      families changes over time and what factors affect the changes in family function
      of multicultural families. METHODS: The study subjects were 62 Asian immigrant
      women married to South Korean men living in South Korea. In a 1st wave study in
      August 2008, the socioeconomic factors and Family Adaptability and Cohesion Scale
      III (FACES III) scores were measured. A 3-year follow-up study was then conducted
      in August 2011, and the results were compared with the 1st wave study results.
      RESULTS: The mean family adaptability score was 24.6 in the 1st wave study and
      26.1 at the 3-year follow-up. The average family cohesion score was 31.0 in the
      1st wave study and 36.7 at the 3-year follow-up. There was a statistically
      significant increase in family cohesion after 3 years (P < 0.001). In multiple
      regression analysis, age difference between husband and wife (P = 0.019) and
      subjective SES (P < 0.001) were found to be significantly correlated with
      positive changes of cohesion scores. DISCUSSION: Family adaptability did not
      change over time; however, conversely, family cohesion increased. The age
      difference between husband and wife and the subjective SES had a positive
      association with the changes in family cohesion.

PMID- 23857755
TI  - Synthesis of renewable fine-chemical building blocks by reductive coupling
      between furfural derivatives and terpenes.
AB  - Sugar and Spice...: The use of renewable resources to produce fine chemicals is
      an underdeveloped area. A waste-free technology will be necessary to further
      convert platform chemicals, readily available from biomass. We show that
      furfurals, which can be obtained from C5 sugars, can be coupled with terpenes in
      up to 95% yield through ruthenium-catalyzed reductive couplings developed by
      Krische et al.

PMID- 23857756
TI  - Protein folding studied by dissolution dynamic nuclear polarization.

PMID- 23857757
TI  - Continuous-flow synthesis of CdSe quantum dots: a size-tunable and scalable
      approach.
AB  - In recent years, continuous-flow/microreactor processing for the preparation of
      colloidal nanocrystals has received considerable attention. The intrinsic
      advantages of microfluidic reactors have opened new opportunities for the size
      controlled synthesis of nanocrystals either in the laboratory or on a large
      scale. Herein, an experimentally simple protocol for the size-tunable continuous
      flow synthesis of rather monodisperse CdSe quantum dots (QDs) is presented. CdSe
      QDs are manufactured by using cadmium oleate as cadmium source, selenium dioxide
      as selenium precursor, and 1-octadecene as solvent. Exploiting selenium dioxide
      as selenium source and 1-octadecene as solvent allows execution of the complete
      process in open air without any requirement for air-free manipulations using a
      glove box or Schlenk line. Continuous-flow processing is performed with a
      stainless steel coil of 1.0 mm inner diameter pumping the combined precursor
      solution through the reactor by applying a standard HPLC pump. The effect of
      different reaction parameters, such as temperature, residence time, and flow
      rate, on the properties of the resulting CdSe QDs was investigated. A temperature
      increase from 240 to 260  degrees C or an extension of the residence time from 2
      to 20 min affords larger nanocrystals (range 3-6 nm) whereas the size
      distribution does not change significantly. Longer reaction times and higher
      temperatures result in QDs with lower quantum yields (range 11-28 %). The quality
      of the synthesized CdSe QDs was confirmed by UV/Vis and photoluminescence
      spectroscopy, small-angle X-ray scattering, and high-resolution transmission
      electron microscopy. Finally, the potential of this protocol for large-scale
      manufacturing was evaluated and by operating the continuous-flow process for 87
      min it was possible to produce 167 mg of CdSe QDs (with a mean diameter of 4 nm)
      with a quantum yield of 28 %. 

PMID- 23857758
TI  - Quest for a good life: spiritual values, life goals, and college students.
AB  - INTRODUCTION: Values and life goals are associated with one's general well-being
      and quality of life. However, there is insufficient documentation about issues
      that are linked with the notions of spiritual values and life goals among college
      students in Asia. This study addressed this lack of research by focusing on the
      spiritual values and life goals among students in Singapore. METHODS: Four
      hundred and ninety structured surveys and 64 follow-up interviews were taken in
      two government-sponsored universities in Singapore. RESULTS: Statistics showed
      that spiritual values were positively correlated with intrinsic goals, which had
      been shown to strongly relate to subjective well-being (SWB). DISCUSSION:
      Developing spiritual values may promote subjective well-being by enabling college
      students to find meaning and purpose in life.

PMID- 23857759
TI  - Two rings too tight: sequential emergency PCI for hemodynamic and arrhythmic
      complications of mitral and tricuspid valve repair.
AB  - New intra-operative mitral regurgitation is an unusual complication of tricuspid
      annuloplasty and maybe ischemic in etiology as a consequence of right coronary
      artery distortion. We report the case of a woman in whom this was treated by
      mitral valve annuloplasty with ensuing hemodynamic instability and ventricular
      arrhythmia secondary to a new left circumflex occlusion. Injury/distortion to
      either of the coronary arteries running in the atrio-ventricular groove is rare,
      and described only several times. To our knowledge, concurrent right coronary
      artery and circumflex artery injury/distortion has not been reported previously.

PMID- 23857760
TI  - Inhibition of miR-92a enhances fracture healing via promoting angiogenesis in a
      model of stabilized fracture in young mice.
AB  - MicroRNAs (miRNAs) are endogenous small noncoding RNAs regulating the activities
      of target mRNAs and cellular processes. Although no miRNA has been reported to
      play an important role in the regulation of fracture healing, several miRNAs
      control key elements in tissue repair processes such as inflammation, hypoxia
      response, angiogenesis, stem cell differentiation, osteogenesis, and
      chondrogenesis. We compared the plasma concentrations of 134 miRNAs in 4 patients
      with trochanteric fractures and 4 healthy controls (HCs), and the levels of six
      miRNAs were dysregulated. Among these miRNAs, miR-92a levels were significantly
      decreased 24 hours after fracture, compared to HCs. In patients with a
      trochanteric fracture or a lumbar compression fracture, the plasma concentrations
      of miR-92a were lower on days 7 and 14, but had recovered on day 21 after the
      surgery or injury. To determine whether systemic downregulation of miR-92a can
      modulate fracture healing, we administered antimir-92a, designed using locked
      nucleic acid technology to inhibit miR-92a, to mice with a femoral fracture.
      Systemic administration of antimir-92a twice a week increased the callus volume
      and enhanced fracture healing. Enhancement of fracture healing was also observed
      after local administration of antimir-92a. Neovascularization was increased in
      mice treated with antimir-92a. These results suggest that plasma miR-92a plays a
      crucial role in bone fracture healing in human and that inhibition of miR-92a
      enhances fracture healing through angiogenesis and has therapeutic potential for
      bone repair.

PMID- 23857761
TI  - Pattern of suicides in 2009: data from the National Suicide Registry Malaysia.
AB  - INTRODUCTION: The National Suicide Registry Malaysia (NSRM) is a nationwide
      system that captures data on completed suicides in Malaysia from all forensic
      departments under the purview of the Ministry of Health Malaysia. METHODS: This
      paper examines all suicidal deaths reported to the NSRM from 1 January 2009 to 31
      December 2009. The relevant variables were recorded in the paper-based Case
      Report Form (CRF) and then entered into the online reporting system for analysis.
      RESULTS: The overall suicide rate for 2009 was 1.18 per 100,000 population (n =
      328). The age range was 14-94 years, with a median of 37 (IQR 24) years. There
      were more men than women, the gender ratio being 2.9:1 (males : females), and the
      majority (89% or 293/328) were Malaysian citizens. Ethnicity-wise, Indians had
      the highest suicide rate of 3.67 per 100,000. The Malays and Bumiputera of Sabah
      and Sarawak had lower rates of 0.32 to 0.37 per 100,000. Mental illness was
      reported in 22% (72/328) of the cases and physical illnesses in 20.4% (67/328).
      Previous suicide attempts were reported in 15.5% (51/328) of cases. History of
      substance abuse was present in 28.7% (83/328). Life events were positive in 41.2%
      (135/328) of cases. DISCUSSION: Malaysia is able to generate statistics on
      suicide by enhancing the collaboration between forensic, psychiatry and clinical
      research agencies. These trends should be monitored to gain a better
      understanding of suicide trends.

PMID- 23857762
TI  - Electrocatalytic hydrogenation of 5-hydroxymethylfurfural in the absence and
      presence of glucose.
AB  - Electrocatalytic hydrogenation of 5-hydroxymethylfurfural (HMF) to 2,5
      dihydroxymethylfuran (DHMF) or other species, such as 2,5-dimethylfuran, on solid
      metal electrodes in neutral media is addressed, both in the absence and in the
      presence of glucose. The reaction is studied by combining voltammetry with on
      line product analysis by using HPLC, which provides both qualitative and
      quantitative information about the reaction products as a function of electrode
      potential. Three groups of catalysts show different selectivity towards: (1) DHMF
      (Fe, Ni, Ag, Zn, Cd, and In), (2) DHMF and other products (Pd, Al, Bi, and Pb),
      depending on the applied potential, and (3) other products (Co, Au, Cu, Sn, and
      Sb) through HMF hydrogenolysis. The rate of electrocatalytic HMF hydrogenation is
      not strongly catalyst-dependent because all catalysts show similar onset
      potentials (-0.5 +/- 0.2 V) in the presence of HMF. However, the intrinsic
      properties of the catalysts determine the reaction pathway towards DHMF or other
      products. Ag showed the highest activity towards DHMF formation (up to 13.1 mM
      cm(-2) with high selectivity> 85%). HMF hydrogenation is faster than glucose
      hydrogenation on all metals. For transition metals, the presence of glucose
      enhances the formation of DHMF and suppresses the hydrogenolysis of HMF. On poor
      metals such as Zn, Cd, and In, glucose enhances DHMF formation; however, its
      contribution in the presence of Bi, Pb, Sn, and Sb is limited. Remarkably, in the
      presence of HMF, glucose hydrogenation itself is largely suppressed or even
      absent. The first electron-transfer step during HMF reduction is not metal
      dependent, suggesting a non-catalytic reaction with proton transfer directly from
      water in the electrolyte.

PMID- 23857763
TI  - Investigation on the influence of a didactic course in psychiatry on attitudes of
      mental illness in Chinese college students.
AB  - INTRODUCTION: With the modernization of Chinese society and increased general
      levels of education, the stigmatization of mental illness may have declined,
      especially among advanced students. However, misunderstandings about mental
      illness may remain and adversely affect service delivery to this population.
      Educational initiatives in psychiatry may support a more accepting and scientific
      understanding of these illnesses among college students. METHOD: Attitudes
      towards mental illness were compared between 161 medical students who received a
      basic 48-hour introductory course in psychiatry and 170 college students who had
      not received such a course using a 43-item questionnaire. Previous factor
      analysis had shown this questionnaire to address four factors: 1. Personal
      willingness to socialize with people with mental illness; 2. Support for
      normalizing relationships and activities of people with mental illness; 3.
      Rejecting supernatural explanations of mental illness; and 4. Agreeing with a
      biopsychosocial view of the etiology of mental illness. Analysis of Co-Variance
      was used to compare the groups on these factors with adjustment for significant
      differences in age and years of education. RESULT: The two groups of students
      scored similarly on the socializing factor (P = 0.252), the rejection of
      supernatural causes factor (P = 0.248) and the normalizing factor (P = 0.362),
      but students who had the didactic psychiatry course scored more positively on the
      biopsychosocial factor (percent difference = 15.06%, P = 0.001). DISCUSSION: A
      single formal psychiatry course may improve understanding of the biopsychosocial
      causes of mental illness but did not affect other attitudinal domains among
      Chinese college students.

PMID- 23857764
TI  - Dehydrogenation mechanism of liquid organic hydrogen carriers: dodecahydro-N
      ethylcarbazole on Pd(111).
AB  - Dodecahydro-N-ethylcarbazole (H12-NEC) has been proposed as a potential liquid
      organic hydrogen carrier (LOHC) for chemical energy storage, as it combines both
      favourable physicochemical and thermodynamic properties. The design of optimised
      dehydrogenation catalysts for LOHC technology requires a detailed understanding
      of the reaction pathways and the microkinetics. Here, we investigate the
      dehydrogenation mechanism of H12-NEC on Pd(111) by using a surface-science
      approach under ultrahigh vacuum conditions. By combining infrared reflection
      absorption spectroscopy, density functional theory calculations and X-ray
      photoelectron spectroscopy, surface intermediates and their stability are
      identified. We show that H12-NEC adsorbs molecularly up to 173 K. Above this
      temperature (223 K), activation of C-H bonds is observed within the five-membered
      ring. Rapid dehydrogenation occurs to octahydro-N-ethylcarbazole (H8-NEC), which
      is identified as a stable surface intermediate at 223 K. Above 273 K, further
      dehydrogenation of H8-NEC proceeds within the six-membered rings. Starting from
      clean Pd(111), C-N bond scission, an undesired side reaction, is observed above
      350 K. By complementing surface spectroscopy, we present a temperature-programmed
      molecular beam experiment, which permits direct observation of dehydrogenation
      products in the gas phase during continuous dosing of the LOHC. We identify H8
      NEC as the main product desorbing from Pd(111). The onset temperature for H8-NEC
      desorption is 330 K, the maximum reaction rate is reached around 550 K. The fact
      that preferential desorption of H8-NEC is observed even above the temperature
      threshold for H8-NEC dehydrogenation on the clean surface is attributed to the
      presence of surface dehydrogenation and decomposition products during continuous
      reactant exposure.

PMID- 23857765
TI  - A self-assembled [Fe(II)12L12] capsule with an icosahedral framework.

PMID- 23857766
TI  - Public speaking fears and their correlates among 17,615 Japanese adolescents.
AB  - INTRODUCTION: Public speaking fears (PSF) are highly prevalent in the general
      population. They are also among the most common symptoms of social anxiety
      disorder, which typically has an adolescent onset and has recently been
      increasingly recognized as a persistent and impairing disorder across various
      cultures in the world. METHODS: This study examined PSF and their associated
      factors among 17,615 adolescents, aged 12-18, in a large-scale school-based
      community survey in Japan. RESULTS: PSF was noted in 7.3% of the students. The
      prevalence was higher among girls than among boys, and it had a tendency to
      decrease with age. Across the gender and age groups, PSF was associated with
      psychopathology, including depression and anxiety, suicidal thoughts, deliberate
      self-harm, violence towards objects and people, and increased difficulties at
      school. DISCUSSION: We should no longer make light of public speaking fears among
      adolescents as transient, common-sense phenomena.

PMID- 23857767
TI  - Ablation of astrocytic laminin impairs vascular smooth muscle cell function and
      leads to hemorrhagic stroke.
AB  - Astrocytes express laminin and assemble basement membranes (BMs) at their
      endfeet, which ensheath the cerebrovasculature. The function of astrocytic
      laminin in cerebrovascular integrity is unknown. We show that ablation of
      astrocytic laminin by tissue-specific Cre-mediated recombination disrupted
      endfeet BMs and led to hemorrhage in deep brain regions of adult mice, resembling
      human hypertensive hemorrhage. The lack of astrocytic laminin led to impaired
      function of vascular smooth muscle cells (VSMCs), where astrocytes have a closer
      association with VSMCs in small arterioles, and was associated with hemorrhagic
      vessels, which exhibited VSMC fragmentation and vascular wall disassembly. Acute
      disruption of astrocytic laminin in the striatum of adult mice also impaired VSMC
      function, indicating that laminin is necessary for VSMC maintenance. In vitro,
      both astrocytes and astrocytic laminin promoted brain VSMC differentiation. These
      results show that astrocytes regulate VSMCs and vascular integrity in small
      vessels of deep brain regions. Therefore, astrocytes may be a possible target for
      hemorrhagic stroke prevention and therapy. 

PMID- 23857768
TI  - Increased CDK1 activity determines the timing of kinetochore-microtubule
      attachments in meiosis I.
AB  - Chromosome segregation during cell division depends on stable attachment of
      kinetochores to spindle microtubules. Mitotic spindle formation and kinetochore
      microtubule (K-MT) capture typically occur within minutes of nuclear envelope
      breakdown. In contrast, during meiosis I in mouse oocytes, formation of the
      acentrosomal bipolar spindle takes 3-4 h, and stabilization of K-MT attachments
      is delayed an additional 3-4 h. The mechanism responsible for this delay, which
      likely prevents stabilization of erroneous attachments during spindle formation,
      is unknown. Here we show that during meiosis I, attachments are regulated by CDK1
      activity, which gradually increases through prometaphase and metaphase I. Partial
      reduction of CDK1 activity delayed formation of stable attachments, whereas a
      premature increase in CDK1 activity led to precocious formation of stable
      attachments and eventually lagging chromosomes at anaphase I. These results
      indicate that the slow increase in CDK1 activity in meiosis I acts as a timing
      mechanism to allow stable K-MT attachments only after bipolar spindle formation,
      thus preventing attachment errors. 

PMID- 23857769
TI  - Kinesin-5/Eg5 is important for transport of CARTS from the trans-Golgi network to
      the cell surface.
AB  - Here we report that the kinesin-5 motor Klp61F, which is known for its role in
      bipolar spindle formation in mitosis, is required for protein transport from the
      Golgi complex to the cell surface in Drosophila S2 cells. Disrupting the function
      of its mammalian orthologue, Eg5, in HeLa cells inhibited secretion of a protein
      called pancreatic adenocarcinoma up-regulated factor (PAUF) but, surprisingly,
      not the trafficking of vesicular stomatitis virus G protein (VSV-G) to the cell
      surface. We have previously reported that PAUF is transported from the trans
      Golgi network (TGN) to the cell surface in specific carriers called CARTS that
      exclude VSV-G. Inhibition of Eg5 function did not affect the biogenesis of CARTS;
      however, their migration was delayed and they accumulated near the Golgi complex.
      Altogether, our findings reveal a surprising new role of Eg5 in nonmitotic cells
      in the facilitation of the transport of specific carriers, CARTS, from the TGN to
      the cell surface. 

PMID- 23857770
TI  - Cell cycle regulation of Greatwall kinase nuclear localization facilitates
      mitotic progression.
AB  - Cell division requires the coordination of critical protein kinases and
      phosphatases. Greatwall (Gwl) kinase activity inactivates PP2A-B55 at mitotic
      entry to promote the phosphorylation of cyclin B-Cdk1 substrates, but how Gwl is
      regulated is poorly understood. We found that the subcellular localization of Gwl
      changed dramatically during the cell cycle in Drosophila. Gwl translocated from
      the nucleus to the cytoplasm in prophase. We identified two critical nuclear
      localization signals in the central, poorly characterized region of Gwl, which
      are required for its function. The Polo kinase associated with and phosphorylated
      Gwl in this region, promoting its binding to 14-3-3epsilon and its localization
      to the cytoplasm in prophase. Our results suggest that cyclin B-Cdk1
      phosphorylation of Gwl is also required for its nuclear exclusion by a distinct
      mechanism. We show that the nucleo-cytoplasmic regulation of Gwl is essential for
      its functions in vivo and propose that the spatial regulation of Gwl at mitotic
      entry contributes to the mitotic switch. 

PMID- 23857771
TI  - CEP120 interacts with CPAP and positively regulates centriole elongation.
AB  - Centriole duplication begins with the formation of a single procentriole next to
      a preexisting centriole. CPAP (centrosomal protein 4.1-associated protein) was
      previously reported to participate in centriole elongation. Here, we show that
      CEP120 is a cell cycle-regulated protein that directly interacts with CPAP and is
      required for centriole duplication. CEP120 levels increased gradually from early
      S to G2/M and decreased significantly after mitosis. Forced overexpression of
      either CEP120 or CPAP not only induced the assembly of overly long centrioles but
      also produced atypical supernumerary centrioles that grew from these long
      centrioles. Depletion of CEP120 inhibited CPAP-induced centriole elongation and
      vice versa, implying that these proteins work together to regulate centriole
      elongation. Furthermore, CEP120 was found to contain an N-terminal microtubule
      binding domain, a C-terminal dimerization domain, and a centriolar localization
      domain. Overexpression of a microtubule binding-defective CEP120-K76A mutant
      significantly suppressed the formation of elongated centrioles. Together, our
      results indicate that CEP120 is a CPAP-interacting protein that positively
      regulates centriole elongation. 

PMID- 23857772
TI  - Kinesin-1-syntaphilin coupling mediates activity-dependent regulation of axonal
      mitochondrial transport.
AB  - Axonal mitochondria are recruited to synaptic terminals in response to neuronal
      activity, but the mechanisms underlying activity-dependent regulation of
      mitochondrial transport are largely unknown. In this paper, using genetic mouse
      model combined with live imaging, we demonstrate that syntaphilin (SNPH) mediates
      the activity-dependent immobilization of axonal mitochondria through binding to
      KIF5. In vitro analysis showed that the KIF5-SNPH coupling inhibited the motor
      adenosine triphosphatase. Neuronal activity further recruited SNPH to axonal
      mitochondria. This motor-docking interplay was induced by Ca(2+) and synaptic
      activity and was necessary to establish an appropriate balance between motile and
      stationary axonal mitochondria. Deleting snph abolished the activity-dependent
      immobilization of axonal mitochondria. We propose an "Engine-Switch and Brake"
      model, in which SNPH acts both as an engine off switch by sensing mitochondrial
      Rho guanosine triphosphatase-Ca(2+) and as a brake by anchoring mitochondria to
      the microtubule track. Altogether, our study provides new mechanistic insight
      into the molecular interplay between motor and docking proteins, which arrests
      axonal mitochondrial transport in response to changes in neuronal activity. 

PMID- 23857773
TI  - The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the
      cell cortex.
AB  - Ezrin, Radixin, and Moesin (ERM) proteins play important roles in many cellular
      processes including cell division. Recent studies have highlighted the
      implications of their metastatic potential in cancers. ERM's role in these
      processes is largely attributed to their ability to link actin filaments to the
      plasma membrane. In this paper, we show that the ERM protein Moesin directly
      binds to microtubules in vitro and stabilizes microtubules at the cell cortex in
      vivo. We identified two evolutionarily conserved residues in the FERM (4.1
      protein and ERM) domains of ERMs that mediated the association with microtubules.
      This ERM-microtubule interaction was required for regulating spindle organization
      in metaphase and cell shape transformation after anaphase onset but was
      dispensable for bridging actin filaments to the metaphase cortex. These findings
      provide a molecular framework for understanding the complex functional interplay
      between the microtubule and actin cytoskeletons mediated by ERM proteins in
      mitosis and have broad implications in both physiological and pathological
      processes that require ERMs. 

PMID- 23857774
TI  - Maximizing DNA yield for epidemiologic studies: no more buffy coats?
AB  - Some molecular analyses require microgram quantities of DNA, yet many
      epidemiologic studies preserve only the buffy coat. In Frederick, Maryland, in
      2010, we estimated DNA yields from 5 mL of whole blood and from equivalent
      amounts of all-cell-pellet (ACP) fraction, buffy coat, and residual blood cells
      from fresh blood (n = 10 volunteers) and from both fresh and frozen blood (n =
      10). We extracted DNA with the QIAamp DNA Blood Midi Kit (Qiagen Sciences,
      Germantown, Maryland) for silica spin column capture and measured double-stranded
      DNA. Yields from frozen blood fractions were not statistically significantly
      different from those obtained from fresh fractions. ACP fractions yielded 80.6%
      (95% confidence interval: 66, 97) of the yield of frozen whole blood and 99.3%
      (95% confidence interval: 86, 100) of the yield of fresh blood. Frozen buffy coat
      and residual blood cells each yielded only half as much DNA as frozen ACP, and
      the yields were more variable. Assuming that DNA yield and quality from frozen
      ACP are stable, we recommend freezing plasma and ACP. Not only does ACP yield
      twice as much DNA as buffy coat but it is easier to process, and its yield is
      less variable from person to person. Long-term stability studies are needed. If
      one wishes to separate buffy coat before freezing, one should also save the
      residual blood cell fraction, which contains just as much DNA. 

PMID- 23857775
TI  - Breastfeeding and adolescent blood pressure: evidence from Hong Kong's "Children
      of 1997" Birth Cohort.
AB  - Observationally, breastfeeding is associated with lower blood pressure in Western
      developed settings, whereas little association exists in developing settings.
      However, postnatal characteristics (e.g., breast milk substitutes, infection
      rates, underweight, and pubertal timing) differ between these settings. We
      examined the association of breastfeeding with blood pressure at ~13 years, using
      multivariable linear regression, in 5,247 term births in 1997 from a population
      representative Hong Kong Chinese birth cohort where socioeconomic patterning of
      breastfeeding differs from that of Western and developing settings but standard
      of living, social infrastructure, and postnatal characteristics are similar to
      those of Western settings. Higher education is associated with short-term
      breastfeeding but recent migration with longer-term breastfeeding. Compared with
      never breastfeeding, exclusive breastfeeding for >=3 months was not associated
      with blood pressure (systolic mean difference = 0.82 mm Hg, 95% confidence
      interval (CI): -0.46, 2.11 and diastolic mean difference = 0.49 mm Hg, 95% CI: 
      0.22, 1.21), nor was partial breastfeeding for any length of time or exclusive
      breastfeeding for <3 months (systolic mean difference = 0.01 mm Hg, 95% CI: 
      0.64, 0.66 and diastolic mean difference = 0.16 mm Hg, 95% CI: -0.20, 0.52),
      adjusted for socioeconomic position and infant characteristics. Lack of
      association in a non-Western developed setting further suggests that observations
      concerning breastfeeding and blood pressure vary with setting, thereby casting
      doubt on causality. 

PMID- 23857776
TI  - Modeling DCE-MRI at low temporal resolution: a case study on rheumatoid
      arthritis.
AB  - PURPOSE: To identify the optimal tracer-kinetic modeling strategy for dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) data acquired at low
      temporal resolution. MATERIALS AND METHODS: DCE-MRI was performed on 13 patients
      with rheumatoid arthritis of the hand before and after anti-tumor necrosis factor
      alpha (TNFalpha) therapy, using a 3D sequence with a temporal resolution of 13
      seconds, imaging for 4 minutes postcontrast injection. Concentration-time curves
      were extracted from regions of interest (ROIs) in enhancing synovium and fitted
      to the 3-parameter modified Tofts model (MT) and the 4-parameter two-compartment
      exchange model (2CXM). To assist the interpretation of the data, the same
      analysis was applied to simulated data with similar characteristics. RESULTS:
      Both models fitted the data closely, and showed similar therapy effects. The MT
      plasma volume was significantly lower than with 2CXM, but the differences in
      permeability and interstitial volume were not significant. 2CXM was less precise
      than MT, with larger standard deviations relative to the mean in most parameters.
      The additional perfusion parameter determined with 2CXM did not provide a
      statistically significant trend due to low precision. CONCLUSION: The standard MT
      model is the optimal modeling strategy at low temporal resolution. Advanced
      models improve the accuracy and generate an additional parameter, but these
      benefits are offset by low precision.

PMID- 23857778
TI  - Reversal of end stage renal disease in patient with transcatheter aortic valve
      replacement.
AB  - Transcatheter aortic valve replacement (TAVR) has become an alternative
      intervention in high-risk and inoperable patients with symptomatic aortic valve
      stenosis. The procedure has been associated with favorable clinical outcomes and
      safety profile in patients with end stage renal disease (ESRD). We describe a
      case of improved kidney function in a patient with ESRD without further need for
      dialysis after TAVR.

PMID- 23857777
TI  - A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer
      growth.
AB  - Changes in the intracellular levels of the essential micronutrient zinc have been
      implicated in multiple diseases including pancreatic cancer; however, the
      molecular mechanism is poorly understood. Here, we report a novel mechanism where
      increased zinc mediated by the zinc importer ZIP4 transcriptionally induces miR
      373 in pancreatic cancer to promote tumour growth. Reporter, expression and
      chromatin immunoprecipitation assays demonstrate that ZIP4 activates the zinc
      dependent transcription factor CREB and requires this transcription factor to
      increase miR-373 expression through the regulation of its promoter. miR-373
      induction is necessary for efficient ZIP4-dependent enhancement of cell
      proliferation, invasion, and tumour growth. Further analysis of miR-373 in vivo
      oncogenic function reveals that it is mediated through its negative regulation of
      TP53INP1, LATS2 and CD44. These results define a novel ZIP4-CREB-miR-373
      signalling axis promoting pancreatic cancer growth, providing mechanistic
      insights explaining in part how a zinc transporter functions in cancer cells and
      may have broader implications as inappropriate regulation of intracellular zinc
      levels plays an important role in many other diseases. 

PMID- 23857779
TI  - Comparisons between autism spectrum disorders and anxiety disorders: findings
      from a clinic sample in Singapore.
AB  - INTRODUCTION: The goals of the present study were to: (i) examine similarities
      and differences in behavioral/emotional problems manifested by children with
      autism spectrum disorder (ASD) and those with anxiety disorder (ANX); (ii) test
      the ability of each of the eight child behavioral checklist (CBCL) and teacher
      report form (TRF) syndrome scales to differentiate the ASD group from the ANX
      group; and (iii) test the ability of an ASD scale derived by Ooi et al. to
      differentiate the ASD group from the ANX group. METHODS: Archival CBCL and TRF
      data from 180 children between 4 and 18 years of age (119 males, 61 females)
      diagnosed with ASD (n = 86) or ANX (n = 94) at an outpatient child psychiatric
      clinic in Singapore were analyzed. RESULTS: The ASD group scored significantly
      higher on Social Problems and Attention Problems but significantly lower on
      Anxious/Depressed and Somatic Complaints than the ANX group. The groups did not
      show significant differences on Withdrawn/Depressed and Thought Problems. Both
      the CBCL and TRF ASD scales were significant predictors of the ASD group, with
      moderate to high sensitivity and specificity. DISCUSSION: Our findings for an
      Asian sample support the diagnostic overlap between ASD and ANX reported for
      Western samples and underscore the importance of treating ASD as both a unitary
      disease and as a web of overlapping configurations of underlying problem
      dimensions.

PMID- 23857781
TI  - Care for the seafarers: a review of mental health in Austronesia.
AB  - INTRODUCTION: Continent-based regional reviews of mental health may not fully
      describe the status of ethnocultural groups that are widely dispersed across
      multiple continents or traditional world regions. Our aim was to describe the
      Austronesians, an ethno-linguistic group living primarily in islands and coastal
      areas in the Pacific and Indian Oceans and Southeast Asia. METHODS: Consulting
      lay databases, we created matrices to describe the demographic, political, and
      socioeconomic profiles of nations with majority and minority indigenous
      Austronesian language-speaking populations. We then accessed the scientific
      literature to describe examples of mental health disparities and/or challenges in
      mental health care delivery. RESULTS: Many Austronesian-speaking people have
      experienced recent or current foreign occupation, lack of recognized sovereignty,
      poverty and low socioeconomic status, and low availability of psychiatric
      resources and providers. An analysis of the biological,
      psychological/psychocultural, and social and environmental impacts (risk or
      protective) on either the prevalence/presentation of mental illness, help-seeking
      behavior or access to mental health care, or management of mental illness
      suggested that there may be relatively unique stressors (e.g. loss of homeland
      from either global warming or nuclear contamination) affecting people in this
      region and certain biological profiles (e.g. susceptibility to obesity and
      metabolic syndrome) that may impact psychiatric treatment. DISCUSSION: Solutions
      to mental health challenges in this world region may include culturally relevant
      and integrative mental healthcare delivery models; resource preserving,
      prevention-focused universal mental healthcare; and technology to improve
      connectivity and increase access to either direct services or workforce-building
      education and training.

PMID- 23857780
TI  - Protective effects of dietary carotenoids on risk of hip fracture in men: the
      Singapore Chinese Health Study.
AB  - Experimental and epidemiologic data suggest that carotenoids in vegetables and
      fruits may benefit bone health due to their antioxidant properties. The
      relationship between dietary total and specific carotenoids, as well as
      vegetables and fruits, and risk of hip fracture was examined among Chinese in
      Singapore. We used data from the Singapore Chinese Health Study, a prospective
      cohort of 63,257 men and women who were of ages 45 to 74 years between 1993 and
      1998. At recruitment, subjects were interviewed on lifestyle factors and medical
      history. Usual diet was measured using a validated food frequency questionnaire.
      During a mean follow-up of 9.9 years, we identified 1630 hip fracture incident
      cases. Among men, consumption of vegetables was associated with lower hip
      fracture risk. Similarly, dietary total carotenoids and specific carotenoids,
      alpha-carotene, beta-carotene, and lutein/zeaxanthin were inversely associated
      with hip fracture risk. Compared to men in the lowest quartile of nutrient
      density, men in the highest quartile had statistically significant 26% to 39%
      risk reduction (all p for trend <0.05). When stratified by body mass index (BMI),
      the greatest protective effects of total vegetables and carotenoids were found in
      men with BMI <20 kg/m(2) (p for trend <=0.004). There was no association between
      dietary carotenoids or vegetables/fruits and hip fracture risk among women. This
      study suggests that adequate intake of vegetables may reduce risk of osteoporotic
      fractures among elderly men and that the antioxidant effects of carotenoids may
      counteract the mechanism of osteoporosis related to leanness.

PMID- 23857782
TI  - The role of brain peptides in the reproduction of blue gourami males
      (Trichogaster trichopterus).
AB  - In all vertebrates, reproduction and growth are closely linked and both are
      controlled by complex hormonal interactions at the brain-pituitary level. In this
      study, we focused on the reciprocal interactions between brain peptides that
      regulate growth and reproductive functions in a teleostei fish (blue gourami
      Trichogaster trichopterus). An increase in gonadotropin-releasing hormone 1
      (GnRH1) gene expression was detected during ontogeny, and this peptide increased
      growth hormone (GH) and beta follicle-stimulating hormone (betaFSH) gene
      expression in pituitary cell culture. However, although no change in gonadotropin
      releasing hormone 2 (GnRH2) gene expression during the reproductive cycle or
      sexual behavior was detected, a stimulatory effect of this peptide on beta
      gonadotropins (betaGtH) gene expression was observed. In addition, pituitary
      adenylate cyclase-activating polypeptide 38 (PACAP-38) inhibited GnRH-analog
      induced betaFSH gene expression, and co-treatment of cells with GnRH-analog and
      PACAP-38 inhibited GnRH-analog-stimulatory and PACAP-38-inhibitory effects on GH
      gene expression. These findings together with previous studies were used to
      create a model summarizing the mechanism of brain peptides (GnRH, PACAP and its
      related peptide) and the relationship to reproduction and growth through
      pituitary hormone gene expression during ontogenesis and reproductive stages in
      blue gourami.

PMID- 23857783
TI  - Mycalol: a natural lipid with promising cytotoxic properties against human
      anaplastic thyroid carcinoma cells.

PMID- 23857785
TI  - Correlation of domestic violence during pregnancy with plasma amino-acid
      neurotransmitter, cortisol levels and catechol-o-methyltransferase Val(158)Met
      polymorphism in neonates.
AB  - INTRODUCTION: To explore the correlation between domestic violence during
      pregnancy and glutamate (Glu), r-aminobutyric acid (GABA), plasma cortisol levels
      and catechol-o-methyltransferase (COMT) gene polymorphism (rs4818) in neonates.
      METHODS: Using the Abuse Assessment Survey, 64 abused pregnant women (DV) and 117
      non-abused pregnant women (non-DV) were screened for two study groups. Blood in
      neonatal umbilical vein was collected immediately after delivery. Plasma Glu,
      GABA, cortisol levels and rs4818 polymorphism in the genotypes and alleles of the
      two neonatal groups were compared. RESULTS: In the DV group, 49 women (76.6%)
      experienced emotional abuse, 29 women (45.3%) experienced sexual abuse, 28
      (43.8%) women experienced emotional abuse plus sexual abuse, and two women (3.1%)
      experienced emotional abuse plus physical abuse. We found that plasma Glu, GABA
      and cortisol levels were higher in DV neonates than in non-DV neonates.
      Furthermore, we observed a significantly positive correlation between maternal
      emotional abuse, sexual abuse and plasma levels of Glu, GABA and cortisol in
      neonates. By genetic analysis we found a significant difference in rs4818SNP
      genotype and allele between the two neonatal groups. The ratios of CC genotype
      and C allele were higher in DV neonates than in non-DV neonates, and the ratios
      of GG genotype and G allele were lower in DV neonates than in non-DV neonates.
      One-way ANOVA test showed that GABA level was lower in CC carriers than CG
      carriers. DISCUSSION: Domestic violence during pregnancy might be associated with
      increased plasma levels of glutamate, GABA, cortisol and COMT gene polymorphism
      in neonates.

PMID- 23857786
TI  - Associations of histone deacetylase-2 and histone deacetylase-3 genes with
      schizophrenia in a Chinese population.
AB  - INTRODUCTION: To explore the association between histone deacetylase-2 (HDAC2)
      and histone deacetylase-3 (HDAC3) gene polymorphisms and schizophrenia. METHODS:
      A total of 208 family trios consisting of fathers, mothers and affected offspring
      with schizophrenia were recruited as our subjects. Four tag SNPs on HDAC2
      (rs10499080, rs6568819, rs2499618 and rs13204445) and two tag SNPs on HDAC3
      (rs11741808, rs2530223) genes were selected. The Mass ARRAY Assay Design software
      (Sequenom) was used to design amplification and allele specific extension
      primers. The Hardy-Weinberg equilibrium (HWE) for genotypic distributions was
      tested using the chi-square goodness-of-fit test. Allelic association for a
      single tag SNP was analyzed by using family-based association tests including the
      haplotype-based haplotype relative risk (HHRR) test and the transmission
      disequilibrium test (TDT). RESULTS: The genotypic distributions of HDAC2 SNPs
      rs6568819, rs2499618 and rs13204445 and HDAC3 SNPs rs11741808 and rs2530223 were
      all in Hardy-Weinberg equilibrium (P > 0.05). HHRR analysis revealed no
      associations between the SNPs and schizophrenia (P > 0.05). In addition, the TDT
      did not show any significant associations between HDAC2 and HDAC3 SNPs and
      schizophrenia (P > 0.05). DISCUSSION: HDAC2 and HDAC3 might not be associated
      with schizophrenia in the Chinese population.

PMID- 23857787
TI  - Significant association of close homologue of L1 gene polymorphism rs2272522 with
      schizophrenia in Qatar.
AB  - INTRODUCTION: Previous reports have found that polymorphisms in the close
      homologue of L1 (CHL1) gene located on chromosome 3p26 are associated with
      schizophrenia among different ethnic populations. The aim of this study was to
      examine the associations of single nucleotides polymorphisms (SNPs) of the CHL1
      gene locus, including rs2055314 (C/T), rs2272522 (C/T) and rs331894 (A/G), with
      schizophrenia in the Qatari population. METHODS: An association case control
      study was carried out on 86 Qatari schizophrenic patients from the Psychiatry
      Hospital, Hammed Medical Corporation, Qatar and 88 Qatari unrelated, healthy,
      control subjects. Schizophrenia was diagnosed according to the Diagnostic and
      Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) criteria for
      schizophrenia by two independent psychiatrists. Genotyping of the SNPs rs2055314
      (C/T), rs2272522 (C/T) and rs331894 (A/G) was conducted using the 5' nuclease
      assay with the TaqMan MGB probe and an ABI 7500. RESULTS: Individuals with the
      rs2272522 TT genotype had approximately 4.2 times greater risk of schizophrenia
      compared to individuals with the CC genotype (OR = 4.21; 95% CI: 1.12-15.53; P =
      0.047). In addition, individuals carrying a T allele of the rs2272522 SNP had a
      significantly increased risk of schizophrenia (1.78 times) among the population
      (P = 0.028). SNPs rs2055314 and rs331894 had no significant association with
      schizophrenia. Pairwise linkage disequilibrium (LD) between the three
      polymorphisms was modest in the schizophrenic group. DISCUSSION: The rs2272522
      polymorphism was found to exhibit a highly significant association with
      schizophrenia in the Qatari population. This finding supports the hypothesis that
      cell adhesion molecules may be involved in the etiology of this disease among
      Qatari patients.

PMID- 23857788
TI  - T102C polymorphism of serotonin 2A type receptor gene confers susceptibility to
      (early onset) schizophrenia in Han Chinese: an association study and meta
      analysis.
AB  - INTRODUCTION: Several lines of evidence have indicated that serotonin 2A receptor
      (HTR2A) may be involved in the pathophysiology of schizophrenia. One functional
      polymorphism in HTR2A (T102C) has been widely investigated; however, the results
      have been inconsistent. The purpose of this study was to evaluate the association
      between HTR2A T02C polymorphism and schizophrenia in a Chinese Han population.
      METHODS: We performed a case-control study, using an early onset sample, which
      may be an attractive subgroup for genetic studies. In addition, we performed a
      meta-analysis of the combined sample groups in Han Chinese. RESULTS: Our study,
      based on 385 schizophrenic patients and 399 controls, found a significant
      genotype-wise association of T102C and schizophrenia (P = 0.02). After applying
      stratified analyses, the dominant model for T allele produced significant
      association (OR = 1.60, 95%CI = 1.11-2.30, P = 0.01). In the meta-analysis
      including all of the published population-based association studies in Han
      Chinese and the present association study, the pooled genotype-wise result in a
      dominant model was statistically significant with a summary OR of 1.25 (95%CI =
      1.04-1.50, P = 0.02). DISCUSSION: Our results suggest that the HTR2A T102C
      polymorphism may confer susceptibility to schizophrenia in Han Chinese.

PMID- 23857789
TI  - DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice.
AB  - INTRODUCTION: Impulsivity in intertemporal choice has been operationalized as
      "delay discounting", referring to the preference for a sooner, smaller reward.
      FK506 binding protein 5 (FKBP5) is a co-chaperone of the glucocorticoid receptor
      (GR). FKBP5 overexpression causes GR resistance, resulting in increased plasma
      cortisol levels. High cortisol levels are associated with low impulsivity in
      intertemporal choice. The aim of this study was to explore the effect of single
      nucleotide polymorphisms (SNPs) in FKBP5 on delay discounting. METHODS: The
      participants consisted of 91 healthy Japanese people (66 males and 25 females
      with a mean age of 40.9 +/- 6.9 years). Each participant completed Kirby's
      monetary choice questionnaire (MCQ) and donated a whole blood sample. Five SNPs
      in FKBP5 were genotyped using the DigiTag2. SNP linear regression analyses with
      100,000 permutations were conducted for the hyperbolic time-discount rate (k).
      RESULTS: Two SNPs were excluded from analysis because of their low minor allelic
      frequencies. The SNP rs1360780 showed a significant association; participants
      with more minor alleles (T) were less impulsive in intertemporal choice for
      delayed gain (multiplicity-corrected P = 0.047). DISCUSSION: The significant SNP
      rs1360780 is located in the region adjacent to the hormone response element (HRE)
      binding sequence where transcription factors bind and alter the transcription of
      FKBP5. A minor allele (T) of rs1360780, which causes FKBP5 overexpression, may
      reduce impulsivity in intertemporal choice (i.e. delay discounting) via GR
      resistance and the subsequent high cortisol levels. This is the first study to
      demonstrate an association between FKBP5 and impulsivity in intertemporal choice.

PMID- 23857790
TI  - Genome-wide DNA methylation patterns in discordant sib pairs with alcohol
      dependence.
AB  - INTRODUCTION: Alcohol dependence is a complex disease caused by a confluence of
      environmental and genetic factors. Epigenetic mechanisms have been shown to play
      an important role in the pathogenesis of alcohol dependence. METHODS: To
      determine if alterations in gene-specific methylation were associated with
      alcohol dependence, a genome-wide DNA methylation analysis was performed on
      peripheral blood mononuclear cells from alcohol-dependent patients and siblings
      without alcohol dependence as controls. The Illumina Infinium Human
      Methylation450 BeadChip was used and gene-specific methylation of DNA isolated
      from peripheral blood mononuclear cells was assessed. Genes ALDH1L2, GAD1, DBH
      and GABRP were selected to validate beadchip results by pyrosequencing. RESULTS:
      Compared to normal controls, 865 hypomethylated and 716 hypermethylated CG sites
      in peripheral blood mononuclear cell DNA in alcohol-dependent patients were
      identified. The most hypomethylated CG site is located in the promoter of SSTR4
      (somatostatin receptor 4) and the most hypermethylated CG site is GABRP (gamma
      aminobutyric acid A receptor). The results from beadchip analysis were consistent
      with that of pyrosequencing. DISCUSSION: DNA methylation might be associated with
      alcohol dependence. Genes SSTR4, ALDH1L2, GAD1, DBH and GABRP may participate in
      the biological process of alcohol dependence.

PMID- 23857792
TI  - Attitudes of primary care physicians towards patients with mental illness in Hong
      Kong.
AB  - INTRODUCTION: This study aims to describe the attitudes of primary care
      physicians towards mental health patients in Hong Kong, especially to examine the
      doctors' views on schizophrenia and depression, and the influence of their
      demographic variables. METHODS: A questionnaire developed by the research team
      was sent to members of Hong Kong College of Family Physicians. Potential
      respondents were allocated on equal basis to one of the two sets of
      questionnaire, set 1 for clinical vignette of schizophrenia and set 2 for
      depression. RESULTS: A response rate of 37% (500 of 1,360) was achieved. There
      were 255 and 245 returned questionnaires for set 1 and set 2, respectively.
      Comparing the two clinical vignettes, there were large differences in their
      willingness to have the patient on practice list for mental issues (40.0% for
      schizophrenia versus 71.5% for depression) and to deal with the patient's needs
      (37.0% versus 60.9%). Multiple ordinal logistic regression analysis showed that
      doctors with the following demographic factors tended to have more worries or
      stigma on mental health patients: "having longer years of practice," "being
      female," "working in hospital," "employed in public sector," and "not having a
      relative/friend with mental health problems." DISCUSSION: Our study shows that
      two-thirds of primary care doctors are prepared to look after patients with
      depression, which is substantially higher than that for schizophrenia. In
      contrast with the Australian findings, the experienced doctors in Hong Kong have
      more negative attitudes towards mental health patients than the younger ones.

PMID- 23857791
TI  - Prevalence of behavioral problems and related family functioning among middle
      school students in an eastern city of China.
AB  - INTRODUCTION: This study was carried out to explore the prevalence of behavioral
      problems among adolescents in junior high school as well as their families'
      levels of function or dysfunction that contribute to children's behavioral
      problems in Mainland China. METHODS: One thousand, four hundred and seventy-six
      adolescents (ages 12-17 years) and their families participated in the study.
      Parents completed a self-administered questionnaire consisting of the Child
      Behavior Checklist (CBCL), Family Assessment Device (FAD) and a number of
      demographic questions. Student's t-tests, chi-square tests and stepwise multiple
      regression models were performed to examine the variables. RESULTS: The estimated
      prevalence of behavioral problems was 10.5% based on the cutoff point for
      behavioral problems according to the CBCL. Behavioral problems identified by the
      CBCL occurred differently at various developmental stages (F = 10.06, P = 0.007).
      The study showed that inappropriate affective responsiveness, poor affective
      involvement and low ability of problem solving in the family were significantly
      associated with increased risk for externalizing behavior problems and total
      behavior problems of boys. Inappropriate affective responsiveness and poor
      communication in the family were significantly associated with increased risk for
      internalizing problems for boys. Poorly established patterns of family behavior
      were important factors contributing to the development of externalizing behavior
      problems, internalizing behavior problems and total behavior problems for girls'.
      DISCUSSION: The present findings suggest that functional levels of family are
      associated with the adolescent's mental health, and that specific family dynamics
      may influence the development of behavioral problems among adolescents in China.

PMID- 23857793
TI  - Diagnostic overlap of depressive, anxiety, stress and somatoform disorders in
      primary care.
AB  - INTRODUCTION: The aim of the present study was to determine the prevalence of
      somatization, anxiety, depression and stress in a primary care population,
      explore their association to psychosocial stressors and determine the diagnostic
      overlap of these four mental disorders. METHODS: This is a prospective cross
      sectional study. A representative sample of 2,150 patients was approached, of
      whom 1,762 patients agreed to participate and responded to the questionnaire
      (81.9%). Anxiety was assessed with the Generalized Anxiety Disorder Scale (GAD
      7). Depression was assessed with the depression module Patients Health
      Questionnaire-8. Somatization was measured with the somatic symptom module PHQ
      15. The Perceived Stress Scale (PSS) instrument was used to identify the stress
      cases. RESULTS: Of the study sample, 23.8% of the total cases were identified as
      probable cases. The prevalence of somatization, depression, anxiety and stress
      was 11.7%, 11.3%, 8.3% and 18.6%, respectively. The specific gender prevalence of
      these four psychological disorders was very similar in men and women: depression
      (11.3% versus 11.3%), anxiety (7.7% versus 8.9%), somatization (12.5% versus
      10.7%) and stress disorders (19.3% versus 17.8%). A significant difference was
      observed in nationality and marital status for depression and anxiety (P < 0.05).
      The age-specific prevalence rate showed a higher prevalence in the age group 45
      54 years: depression (13.3%), anxiety (9.5%), somatization (12.8%) and stress
      (20.4%). Unable to control worries (69.2%) was the worst symptom for anxiety
      disorders, while the majority of the depressed patients wanted to hurt themselves
      (71.9%). Stomach pain (46.1%) was the most common symptom in somatic patients.
      Most of the patients experiencing stress could not cope with their daily duties
      (65.9%). There was a high comorbidity rate of depression, anxiety, somatization
      and stress observed in the studied population (9.3%). CONCLUSION: The prevalence
      of somatization and depression was similar, but the prevalence of stress was
      higher in inpatient patients. Somatization, depression, anxiety and stress
      disorders co-occurred at higher rate in the study sample.

PMID- 23857794
TI  - Long- and short-term inpatients with schizophrenia in China: implications for
      community-based service development.
AB  - INTRODUCTION: There is an increasing interest in the patterns of mental health
      care of people with serious mental illnesses in China, where outpatient and
      community-based care are not fully developed and long-term hospitalization is
      still not uncommon. Comparison of sociodemographic and clinical characteristics
      of long-term and short-term inpatients diagnosed with schizophrenia can be
      informative about pattern of treatment and their relationship to services needs.
      METHODS: Seventy-three long-term schizophrenia inpatients (current length of stay
      of more than 5 years) were compared to 116 short-term schizophrenia inpatients
      (current length of stay of 30 days or less) assessed with the Individual
      Background Questionnaire, the Positive and Negative Syndrome Scale (PANSS) and
      the Social Support Rating Scale (SSRS). RESULTS: There was no significant
      difference between the groups on the total PANSS symptom score but the short-term
      inpatients scored significantly higher than their long-term counterparts on the
      Positive Syndrome sub-scale and the SSRS and lower on the Negative Syndrome sub
      scale. DISCUSSION: Differences in symptomatology and social functioning may be
      related to better medication adherence and more extended social isolation among
      long-term inpatients while the increased positive symptoms are likely to reflect
      more acute disease process in short-term inpatients, and possibly poorer
      medication adherence. These differences may be especially pronounced in
      developing countries like China in which community-based services need to be more
      fully developed to facilitate medication adherence and prevent relapse, and to
      support community adjustment of socially isolated patients who otherwise require
      hospitalization.

PMID- 23857795
TI  - Preliminary Turkish study of psychiatric in-patients' competence to make
      treatment decisions.
AB  - INTRODUCTION: Competence is a prerequisite for informed consent. Patients who are
      found to be competent are entitled to accept or refuse the proposed treatment. In
      recent years, there has been an increased interest in studies examining
      competence for treatment in psychiatric patients. In this study, we aimed to
      investigate the decision-making competencies of inpatients with a range of
      psychiatric diseases. METHODS: This study was carried out at the psychiatry
      clinic of Kocaeli University Hospital in Turkey from June 2007 to February 2008.
      Decision-making competence was assessed in 83 patients using the MacArthur
      Competence Assessment Tool-Treatment (MacCAT-T). RESULTS: The study groups
      consisted of patients with mood (39.8%), psychotic (27.7%) and anxiety disorders
      (18.1%), and alcohol/substance addiction (14.5%). There was a significant
      relation between decision-making competence and demographic and clinical
      characteristics. Appreciation of the given information was more impaired in
      psychotic disorder patients than in other patients, but understanding and
      reasoning of the given information was similar in all groups. DISCUSSION: These
      results reveal the importance of evaluating decision-making competencies of
      psychiatric patients before any treatment or intervention is carried out to
      ascertain their ability to give informed consent to treatment. Institutional and
      national policies need to be determined and put into practice relating to the
      assessment and management of competence in patients with psychiatric disorders.

PMID- 23857796
TI  - Risk personality traits of Internet addiction: a longitudinal study of Internet
      addicted Chinese university students.
AB  - INTRODUCTION: As the world's fastest growing "addiction", Internet addiction is
      still controversial. The present study aimed to examine the potential personality
      predictors of Internet addicts. METHODS: Eight hundred and sixty-eight students
      were tested using the Eysenck Personality Questionnaire after they had just
      entered university. Two years later, 49 were found to be addicted to the Internet
      as defined by high Internet addiction test scores. Comparisons of means and
      logistic regression analysis were used to explore their relationship. RESULTS:
      Students addicted to the Internet showed higher Neuroticism/Stability scores,
      higher Psychoticism/Socialization scores, and lower Lie scores than their normal
      peers before their addiction. Regression results showed that Internet addiction
      was accounted by three independent variables: Neuroticism/Stability,
      Psychoticism/Socialization, and Lie. CONCLUSION: These results suggest that the
      risk personality traits of Internet addiction include neuroticism, psychoticism,
      and immaturity.

PMID- 23857798
TI  - In healthy adults, biological activity of vitamin D, as assessed by serum PTH, is
      largely independent of DBP concentrations.
AB  - Vitamin D insufficiency, as measured by 25-hydroxyvitamin D (25[OH]D) levels, has
      been associated with important health outcomes. The majority of vitamin D in
      circulation is bound to vitamin D-binding protein (DBP) and albumin, and recent
      genetic studies have demonstrated that serum DBP is a major determinant of
      25(OH)D concentrations in adults. The impact of circulating DBP levels on vitamin
      D's biologic action, is unclear, but is of particular relevance to vitamin D
      epidemiology, because a lack of control for DBP levels could strongly influence
      the association of vitamin D with disease. Serum parathyroid hormone (PTH) levels
      can act as a biological readout of 25(OH)D activity. We therefore assessed the
      relationship between serum total and free 25(OH)D and PTH with and without
      adjusting for DBP, in 2073 subjects of European descent. Total 25(OH)D levels
      correlated positively (r = 0.19, p = 1.8 * 10(-17)) with DBP, whereas the free
      25(OH)D correlated negatively (r = -0.14, p = 5.0 * 10(-12)). Total and free
      25(OH)D levels correlated negatively with PTH (r = -0.29, p = 1.3 * 10(-39); r = 
      0.26, p = 1.9 * 10(-33), respectively). Including age, body mass index (BMI),
      sex, estimated glomerular filtration rate, calcium, and season of blood draw as
      covariates, total 25(OH)D levels were significantly associated with log
      transformed PTH (lnPTH) levels (linear term: beta = -0.010, p < 0.0001, squared
      term: beta = 0.00004, p < 0.0001) and this association was not changed by
      adjusting for DBP. These findings provide evidence that in a largely vitamin D
      sufficient cohort, the biological effect of vitamin D on PTH levels is mainly
      independent of DBP concentration. Accordingly, this study may provide useful
      information for studies investigating the relationship between vitamin D, DBP,
      and disease.

PMID- 23857797
TI  - Compressed sensing reconstruction for undersampled breath-hold radial cine
      imaging with auxiliary free-breathing data.
AB  - PURPOSE: To improve compressed sensing (CS) reconstruction of accelerated breath
      hold (BH) radial cine magnetic resonance imaging (MRI) by exploiting auxiliary
      data acquired between different BHs. MATERIALS AND METHODS: Cardiac function is
      usually assessed using segmented cine acquisitions over multiple BHs to cover the
      entire left ventricle (LV). Subjects are given a resting period between adjacent
      BHs, when conventionally no data are acquired and subjects rest in the scanner.
      In this study the resting periods between BHs were used to acquire additional
      free-breathing (FB) data, which are subsequently used to generate a sparsity
      constraint for each cardiac phase. Images reconstructed using the proposed
      sparsity constraint were compared with conventional CS using a composite image
      generated by averaging different cardiac phases. The efficacy of the proposed
      reconstruction was compared using indices of LV function and blood-myocardium
      sharpness. RESULTS: The proposed method provided accurate LV ejection fraction
      measurements for 33% and 20% sampled datasets compared with fully sampled
      reference images, and showed 14% and 11% higher blood-myocardium border sharpness
      scores compared to the conventional CS. CONCLUSION: The FB data acquired during
      resting periods can be efficiently used to improve the image quality of the
      undersampled BH data without increasing the total scan time.

PMID- 23857799
TI  - Construction of Optically Active Quaternary Propargyl Amines by Highly
      Enantioselective Zinc/BINOL-Catalyzed Alkynylation of Ketoimines.
AB  - A general and efficient method for the highly enantioselective alkynylation of
      ketoimines through a zinc/1,1'-bi-2-naphthol (BINOL)-catalyzed process has been
      developed. A variety of ketoimines, including alpha-fluoroalkyl alpha-imine
      esters, alpha-aryl alpha-imine esters, and trifluoromethyl aryl ketoimines, are
      applicable and provide their corresponding quaternary propargyl amines in
      excellent yields with high ee values (up to 99 % ee). Both the steric and
      electronic effects of substituents at the 3,3' positions of BINOL are critical
      for the reaction efficiency and enantioselectivity. To demonstrate the usefulness
      of the method, (R)-alpha-CF3 alpha-proline has been prepared in a highly
      efficient manner. The notable features of this protocol are its broad substrate
      scope, high reaction efficiency (up to 99 %) and enantioselectivity (up to 99 %
      ee), low catalyst loading (5 mol % of BINOL derivative), and mild reaction
      conditions.

PMID- 23857800
TI  - One-year follow-up study of psychotic patients treated with blonanserin: a case
      series.
AB  - INTRODUCTION: Blonanserin is a relatively new atypical antipsychotic drug, and
      has been used in Korea and Japan for 1 and 3 years, respectively. Therefore, the
      clinical characteristics of blonanserin remain unclear. In this study, to clarify
      the features of blonanserin, we performed prospective and long-term comparative
      investigations of patients treated with blonanserin. METHODS: We followed 10
      psychiatric patients who were switched to blonanserin from other antipsychotics
      for 1 year (schizophrenia: 8; mental retardation: 2). In the light of quality of
      life, we focused on adverse effects of patients during the follow-up. RESULTS: In
      the long-term follow-up, (i) hyperprolactinemia is more frequently in risperidone
      than in blonanserin; however, it is more often in blonanserin than in olanzapine;
      and (ii) weight gain is more common in olanzapine than in blonanserin.
      DISCUSSION: We switched to blonanserin from other antipsychotic drugs within the
      same case, and then followed the case for 1 year. We consider that long-term
      observations within the same case lead to obvious comparisons among drugs. On the
      basis of our findings, we conclude that blonanserin may be useful for the
      maintenance treatment of schizophrenia without inducing hyperprolactinemia and
      weight gain.

PMID- 23857801
TI  - Cost-analysis of percutaneous pulmonary valve implantation compared to surgical
      pulmonary valve replacement.
AB  - OBJECTIVES: To perform cost evaluation and economic modeling of percutaneous
      pulmonary valve implantation (PPVI) compared to surgical revision. BACKGROUND:
      While, PPVI appears to be a viable alternative to surgical conduit revision in
      select patients with right ventricular outflow tract anomalies, its overall
      economic burden has yet to be determined. METHODS AND RESULTS: We examined the
      first 17 patients who underwent PPVI at our institution and compared them with
      the most-recently placed surgical valves. Economic data were obtained from the
      actual procedural and in-hospital charges and used as the base estimates for 5-
      and 10-year future modeling with appropriate sensitivity analysis. Median total
      hospital and procedural charges incurred by the patient were significantly higher
      for the surgical valve compared with PPVI ($126,406 +/- $38,772 vs. $80,328 +/-
      $17,387, P < 0.001). Median total societal charges were also higher for the
      surgical valve ($129,519 +/- $39,021 vs. $80,939 +/- $17,334, P < 0.001) owing to
      an average wage loss of $3,113 for surgical patients, contrasted to $611 who
      underwent PPVI, and a shorter length of stay (1.0 +/- 0 vs. 5.7 +/- 2.2, P
      <0.001) for PPVI. Sensitivity analysis determined that PPVI would need to fail at
      a rate of 17% per year (or 93% at 10 years) to lose its cost advantage.
      CONCLUSIONS: PPVI holds a significant cost advantage over the surgical approach,
      fewer hospital days, and incurs less patient wage loss. Furthermore, it would
      need to have a very high failure rate at 10 years to lose its cost advantage.

PMID- 23857802
TI  - Forensic psychiatry in Singapore.
AB  - Singapore is a geographically small nation-state that has transformed itself from
      a third-world country to a developed nation after attaining political
      independence 46 years ago. The pace of change has been tremendous and mental
      health care is no exception. This paper provides an overview of mental health
      care and a review of key mental health legislation, including a National Mental
      Health Blueprint that was rolled out in 2007. On this background, the paper
      focuses on a description of forensic psychiatric services in Singapore. The role
      of the Department of Forensic Psychiatry at the Institute of Mental Health, which
      is the only forensic psychiatry department in the country, will be highlighted.
      Civil commitment and the treatment of unfit accused persons and insanity
      acquittees is reviewed. The role of forensic psychiatric assessments in the
      Singapore courts is examined. The application of the insanity and diminished
      responsibility defenses are reviewed. A trend is identified in the Singapore
      courts towards a more rehabilitation-focused sentencing approach and the role
      that forensic psychiatric assessments play in cases involving mentally disordered
      offenders is highlighted. 

PMID- 23857803
TI  - Dens invaginatus in ancient Chinese teeth of 2,000 years ago.
AB  - Dens invaginatus (DI) is a developmental anomaly of teeth. Here we observed the
      characteristics of DI in 517 permanent teeth from 67 ancient Chinese people using
      micro-computed tomography (micro-CT) scanning techniques. The individuals were
      excavated from Shaanxi province of China and identified to be about 2,000 years
      old. Four DI categories are proposed to distinguish the different types of DI.
      The invaginated lingual fossa is classified into three classes. The overall
      prevalence of DI in 67 individuals was 31.34% (21 of 67). DI was found in 25 of
      517 teeth (4.83%). All affected teeth were maxillary lateral incisors. The
      invaginated lingual fossa (Type I DI) occurred most frequently (84%), followed by
      radicular grooves (Type II; 16%), while Type III and Type IV were not found in
      the present study. Some of fossae correspond with radicular grooves (8 of 21; 3
      located at mesial, 5 were distal). The bilateral incidence of DI was 19.05%.
      Comparing our results to those of a retrospective survey of DI from 1873 to
      present, we found a higher rate of DI in the excavated teeth of Chinese
      individuals 2,000 years ago. The use of the micro-CT technique and ethnic origin
      might have contributed to the higher incidence of DI.

PMID- 23857804
TI  - Academic psychiatry across the Pacific: challenges and opportunities for the
      Pacific-Rim College of Psychiatrists.
AB  - There is cautious optimism that the economic growth around the Pacific-Rim, will
      stir opportunities to redress the mental health resource deficiencies and
      inequity of access to services. Many psychiatric services are without
      psychiatrists and the primary care doctor or nurse is the key mental health
      professional. One of the challenges is a paucity of training opportunities and a
      dearth of trainers. Primary care psychiatry training should be the focus of
      educational programs. Collaboration in research has been gathering momentum in
      recent years. The Research in East Asia of Psychotropic Prescription (REAP)
      includes a consortium of eight countries in Asia. More recently, there have been
      workshops organized for leadership training of young psychiatrists. The Pacific
      Rim College of Psychiatrists and Asia-Pacific Psychiatry journal can be a
      platform for education and research. The myriad cultures and wide expertise
      across the Pacific-Rim will make collaboration more exciting and challenging. 

PMID- 23857805
TI  - Autism spectrum disorder in Chinese populations: a brief review.
AB  - This review summarizes the published work on the prevalence and incidence rates
      of autism spectrum disorder (ASD) in Chinese populations. The authors searched
      MEDLINE, Web of Science and the PsycINFO database and identified seven studies
      that were published in the English language. In mainland China, Li and colleagues
      reported an autism prevalence rate of 2.38/10,000 but admitted the possibility of
      underestimation. A higher prevalence of 11/10,000 was reported by Zhang and Ji
      based on a survey that was conducted in Tianjin, China. In Taiwan, Chien and
      colleagues reported that the cumulative prevalence of ASD increased from 1.79 to
      28.72/10,000 from 1996 to 2005 and the annual incidence rate increased from 0.91
      to 4.41/10,000 per year from 1997 to 2005. Another study based on the Taiwan
      national health insurance database reported a high prevalence rate of
      122.8/10,000 for the year 2007. Two studies based on the Taiwan national
      disability registry data reported an increasing trend of ASD for the period 2000
      2007 and 2004-2010, respectively. In Hong Kong, Wong and colleagues estimated
      that the incidence of ASD was 5.49/10,000 and the average prevalence over the
      1986-2005 period was 16.1/10,000. We identified 12 studies through the searching
      of Chinese databases. The prevalences among these studies varied from 2.8 to
      29.5/10,000. While existing data appear to suggest, it remains unclear whether
      there is a true rise in the prevalence of ASD in ethnic Chinese population across
      geographic sites. More collaborative research on this topic should be conducted
      in the future. 

PMID- 23857806
TI  - Validation of the nine-item Patient Health Questionnaire to screen for major
      depression in a Chinese primary care population.
AB  - INTRODUCTION: The aim of this study was to examine the reliability and validity
      of the nine-item Patient Health Questionnaire (PHQ-9) for screening depression in
      Chinese primary care settings. METHODS: In 100 randomly selected primary care
      clinics (PCC) of Hangzhou city, we recruited 2,639 patients (aged >=18 years) and
      applied the PHQ-9 to screen for depression. Then, 280 of them were further
      interviewed with the Structured Clinical Interview for Diagnostic and Statistical
      Manual Disorders (SCID) for the diagnosis of major depression. Statistical
      analysis of the demographic data, reliability, validity and receiver-operator
      curve were performed. RESULTS: The mean administration time was 7 minutes, and
      the Cronbach's alpha was 0.89. The optimal cutoff score of 10 on the PHQ-9
      revealed a sensitivity of 0.87, specificity of 0.81, and positive likelihood
      ratio of 5.04. The area under the receiver-operator curve in this study was 0.91
      (95% confidence interval, 0.87-0.94). DISCUSSION: The PHQ-9 performs well and has
      acceptable psychometric properties for screening of patients with depression in a
      Chinese primary care population.

PMID- 23857807
TI  - Multi-components of evoked-brain potentials in deficit and nondeficit
      schizophrenia.
AB  - INTRODUCTION: The present study aims to detect the specific and common impairment
      index relative to evoked brain potentials (EBPS ) in deficit schizophrenia (DS)
      and nondeficit schizophrenia (NDS), and investigates the relationship between
      EBPs and clinical variables. METHODS: The study used EBPs in 21 patients with DS,
      38 patients with NDS, and 50 healthy controls (HCs) to investigate P300 waves,
      mismatch negative (MMN), sensory gating (SG) P50 and contingent negative
      variation (CNV). A comparison of three groups and the relationship between EBPs
      and clinical variables were performed using general linear model analyses and
      partial correlation, respectively. RESULTS: Compared with HCs, both groups of
      patients showed delayed N1 , N2 , and P3a latency, and reduced N1 and N2
      amplitude. The MMN showed delayed latency. The P50 ratios and the inhibited
      ratios were impaired, whereas SG loss ratios increased. CNV amplitude was
      reduced. Compared with HCs, NDS showed delayed latency of S2'-C in CNV, whereas
      DS showed shortened latency. Only NDS, when compared with HCs, showed delayed
      latency of P3b , Also, only DS, when compared with HCs, showed delayed latency of
      point A in CNV. Latency of point A in CNV of DS, correlated with a poorer Global
      Assessment of Functioning Scale (6 weeks) and was independent of clinical
      characteristics. DISCUSSION: Schizophrenia represents a clinical syndrome with
      shared impairments in brain function, whereas DS is a relatively homogeneous
      subgroup of schizophrenia with unique pathophysiological changes.

PMID- 23857808
TI  - Decreased cardiac vagal control in drug-naive patients with panic disorder: a
      case-control study in Taiwan.
AB  - INTRODUCTION: Cardiac autonomic dysregulation has been proposed in panic disorder
      (PD), but the results are mixed. Analyses with larger sample sizes and better
      methodology are needed. METHODS: Forty-eight drug-naive individuals with PD and
      202 healthy volunteers were recruited for a case-control analysis. We used the
      Hamilton Anxiety Rating Scale and the Beck Anxiety Inventory to assess anxiety
      severity. Cardiac autonomic function was evaluated by measuring heart rate
      variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The
      obtained results were evaluated in association with personality traits assessed
      by the Tridimensional Personality Questionnaire. RESULTS: Patients exhibited
      reduced mean RR interval (816.94 +/- 135.92 versus 873.47 +/- 143.36 ms, P =
      0.014) and HRV levels (Var 6.37 +/- 1.32 versus 7.38 +/- 0.95, LF 4.90 +/- 1.63
      versus5.82 +/- 1.11 and HF 4.57 +/- 1.53 versus 5.62 +/- 1.24 [ln(ms2)], all P <
      0.001) as compared to controls, which mainly suggested a reduction in cardiac
      vagal control in PD. The anxiety severity was negatively correlated with HRV
      levels (r = -0.29 for Var, r = -0.22 for LF and r = -0.28 for HF, all P < 0.001).
      The harm avoidance score (which has been suggested to be associated with
      serotonergic activity) was associated with decreased HRV levels (r = -0.22 for
      Var, P < 0.01, r = -0.14 for LF, P < 0.05 and r = -0.17 for HF, P < 0.01).
      DISCUSSION: This study demonstrates that PD is associated with cardiac autonomic
      dysregulation, highlighting the importance of assessing HRV in PD patients.

PMID- 23857809
TI  - Effectiveness of computerized cognitive rehabilitation training on
      symptomatological, neuropsychological and work function in patients with
      schizophrenia.
AB  - INTRODUCTION: There has been plenty of interest in cognitive rehabilitation for
      schizophrenia here in Korea since the year 2000. But the efficacy studies of
      cognitive remediation intervention are still deficient. The primary purpose of
      this study was to develop a computer-assisted cognitive remediation program and
      conduct a clinical trial in a group of schizophrenic patients. METHODS: Sixty
      patients with schizophrenia were randomly assigned to a computerized cognitive
      rehabilitation (Cog-trainer) group plus usual rehabilitation (UR) or to a usual
      rehabilitation (UR) group only. Clinical, neuropsychological and functional
      outcome variables were assessed at baseline and after intervention. The Cog
      trainer group received 20 sessions of computerized cognitive remediation training
      over 3 months. This training program consists of 10 units, with each unit being
      divided into three stages: (i) practice; (ii) application; and (iii) advanced.
      RESULTS: Compared to the UR group, the Cog-trainer exhibited a significant
      improvement in attention, concentration and working memory. The Cog-trainer group
      also showed improvement in the work quality subscale of the work behavior
      inventory. However, there were no significant benefits of computerized cognitive
      remediation where symptoms were concerned. DISCUSSION: These results indicate
      that computerized cognitive rehabilitation training can contribute to an
      improvement in the cognitive function of people with schizophrenia. The changes
      in cognitive outcomes can also contribute to improvement in job functioning.
      Further study of generalization to other functional outcome measures will be
      necessary. Long-term follow-up studies are needed to confirm the maintenance of
      such improvements.

PMID- 23857810
TI  - Development and validation of 26-item dysfunctional attitude scale.
AB  - INTRODUCTION: Dysfunctional Attitude Scale is one of the most common instruments
      used to assess cognitive vulnerability. This study aimed to develop and validate
      a short form of Dysfunctional Attitude Scale appropriate for an Iranian clinical
      population. METHODS: Participants were 160 psychiatric patients from medical
      centers affiliated with Isfahan Medical University, as well as 160 non-patients.
      Research instruments were clinical interviews based on the Diagnostic and
      Statistical Manual-IV-TR, Dysfunctional Attitude Scale and General Heath
      Questionnaire (GHQ-28). Data was analyzed using multicorrelation calculations and
      factor analysis. RESULTS: Based on the results of factor analysis and item-total
      correlation, 14 items were judged candidates for omission. Analysis of the 26
      item Dysfunctional Attitude Scale (DAS-26) revealed a Cronbach's alpha of 0.92.
      Evidence for the concurrent criterion validity was obtained through calculating
      the correlation between the Dysfunctional Attitude Scale and psychiatric
      diagnosis (r = 0.55), GHQ -28 (r = 0.56) and somatization, anxiety, social
      dysfunction, and depression subscales (0.45,0.53,0.48, and 0.57, respectively).
      Factor analysis deemed a four-factor structure the best. The factors were labeled
      as success-perfectionism, need for approval, need for satisfying others, and
      vulnerability-performance evaluation. DISCUSSION: The results showed that the
      Iranian version of the Dysfunctional Attitude Scale (DAS-26) bears satisfactory
      psychometric properties suggesting that this cognitive instrument is appropriate
      for use in an Iranian cultural context.

PMID- 23857811
TI  - Developing a culturally appropriate mental health care service for Samoa.
AB  - Mental Health Care Services are part of the National Health Services for Samoa.
      Their function is to provide mental health care services to the population of
      Samoa, which numbers 180,000 people. However, like many other countries in the
      Pacific region, mental health is considered a low priority. The mental health
      budget allocation barely covers the operation of mental health care services.
      More broadly, there is a lack of political awareness about mental health care
      services and mental health rarely becomes an issue of deliberation in the
      political arena. This article outlines the recent development of mental health
      care services in Samoa, including the Mental Health Policy 2006 and Mental Health
      Act 2007. It tells the story of the successful integration of aiga (family) as an
      active partner in the provision of care, and the development of the Aiga model
      utilizing Samoan cultural values to promote culturally appropriate family-focused
      community mental health care for Samoa. Mental Health Care Services today
      encompass both clinical and family-focused community mental health care services.
      The work is largely nurse-led. Much has been achieved over the past 25 years.
      Increased recognition by government and increased resourcing are necessary to
      meet the future health care needs of the Samoan people. 

PMID- 23857812
TI  - Maternal psychological state during the transition to motherhood: a longitudinal
      study.
AB  - INTRODUCTION: The aim of this study was to investigate the psychological state of
      women and its associated factors in the third trimester of pregnancy and at 8
      weeks postpartum and to explore the changes in psychological state between these
      two time points. METHODS: This survey study was carried out on 358 pregnant women
      visiting urban health centers in Shahroud, northeast Iran, in 2011. The women
      were followed at 8 weeks postpartum. In the third trimester of pregnancy, the
      participants completed the 28-item General Health Questionnaire (GHQ-28) and two
      other questionnaires on sociodemographic characteristics and frequent
      psychosocial stressors. They also completed the GHQ-28 and an obstetric
      information form at 8 weeks postpartum. The cutoff score for GHQ-28 in Iran has
      been calculated as 24, which denotes probable psychological health problems.
      RESULTS: The mean total GHQ score decreased from 23.7 in the third trimester of
      pregnancy to 18.8 postpartum (P < 0.001). The proportion of women with a GHQ-28
      score of 24 or higher in the third trimester of pregnancy and postpartum were 42%
      and 26%, respectively. Multiparity, caring for other family members, financial
      problems, and anxiety about personal and fetal health were the predictors of
      psychological health problems in the third trimester of pregnancy. The two
      predictors for postpartum psychological health problems were psychological health
      problems in the third trimester of pregnancy and the method of infant feeding at
      8 weeks postpartum. DISCUSSION: The prevalence of psychological symptoms was high
      among women in the third trimester of pregnancy. Psychological state of women
      improved after childbirth.

PMID- 23857813
TI  - Increased high-sensitivity C-reactive protein levels in Taiwanese schizophrenic
      patients.
AB  - INTRODUCTION: Schizophrenia is associated with the activation of the
      immune/inflammatory system. C-reactive protein (CRP), a positive acute phase
      protein, may be associated with schizophrenia and antipsychotic treatment.
      METHODS: The serum high-sensitivity CRP (hsCRP) levels of 36 schizophrenic
      patients undergoing clozapine, olanzapine or risperidone treatment and 36 sex
      matched healthy subjects were collected. The difference in hsCRP levels between
      the schizophrenic and the control groups was estimated using ancova. anova was
      performed to examine the differences in the hsCRP levels between three
      antipsychotic groups (clozapine, olanzapine and risperidone). RESULTS: ancova
      adjusted for age and body mass index (BMI) revealed a significant increase in the
      hsCRP levels in the schizophrenic group (1.4 mg/L, SD =1.5 mg/L) in comparison
      with the control group (0.9 mg/L, SD = 1.4 mg/L) (P = 0.013). anova revealed no
      statistical difference of age, BMI and hsCRP in three antipsychotic groups (P =
      0.83, 0.90 and 0.71, respectively). DISCUSSION: The elevation of CRP level is
      seen in chronic schizophrenia under antipsychotic treatment; however, studies
      with a larger sample size are required to confirm these results.

PMID- 23857814
TI  - Screening for postnatal depression in Chinese-speaking women using the Hong Kong
      translated version of the Edinburgh Postnatal Depression Scale.
AB  - INTRODUCTION: The Edinburgh Postnatal Depression Scale (EPDS) may not be a
      uniformly valid postnatal depression (PND) screen across populations. We
      evaluated the performance of a Chinese translation of 10-item (HK-EPDS) and six
      item (HK-EPDS-6) versions in post-partum women in Singapore. METHODS: Chinese
      speaking post-partum obstetric clinic patients were recruited for this study.
      They completed the HK-EPDS, from which we derived the six-item HK-EPDS-6. All
      women were clinically assessed for PND based on Diagnostic and Statistical
      Manual, Fourth Edition-Text Revision criteria. Receiver-operator curve (ROC)
      analyses and likelihood ratio computations informed scale cutoff choices.
      Clinical fitness was judged by thresholds for internal consistency [alpha >=
      0.70] and for diagnostic performance by true-positive rate (>85%), false-positive
      rate (<=10%), positive likelihood ratio (>1), negative likelihood ratio (<0.2),
      area under the ROC curve (AUC, >=90%) and effect size (>=0.80). RESULTS: Based on
      clinical interview, prevalence of PND was 6.2% in 487 post-partum women. HK-EPDS
      internal consistency was 0.84. At 13 or more cutoff, the true-positive rate was
      86.7%, false-positive rate 3.3%, positive likelihood ratio 26.4, negative
      likelihood ratio 0.14, AUC 94.4% and effect size 0.81. For the HK-EPDS-6,
      internal consistency was 0.76. At 8 or more cutoff, we found a true-positive rate
      of 86.7%, false-positive rate 6.6%, positive likelihood ratio 13.2, negative
      likelihood ration 0.14, AUC 92.9% and effect size 0.98. DISCUSSION: The HK-EPDS
      (cutoff >=13) and HK-EPDS6 (cutoff >=8) are fit for PND screening for general
      population post-partum women. The brief six-item version appears to be clinically
      suitable for quick screening in Chinese speaking women.

PMID- 23857815
TI  - Characteristics of Wenchuan earthquake victims who remained in a government
      supported transitional community.
AB  - INTRODUCTION: The Chinese government and provincial authorities built a large
      number of temporary communities to shelter survivors after the May 2008 Wenchuan
      earthquake. Most residents left within a few months but others remained. This
      study describes the characteristics and psychological status of those victims who
      remained in a government-supported transitional community 12 months post
      earthquake compared to residents who departed prior to that time. METHODS: Two
      groups of survivors of Wenchuan earthquake who resided in a transitional
      community were enrolled: 86 in December 2008 and 151 in February 2009. We
      assessed their mental distress, symptoms of depression and post-traumatic stress
      disorder and suicide risk. Forty-three and 46 members of the two groups,
      respectively, had departed the transitional community at 1 year post-earthquake.
      RESULTS: In both groups, most of the survivors who remained in the community 1
      year post-earthquake were older, female, with a lower education level and more
      serious personal losses. They had scored higher on self-report measures
      reflecting distressing symptoms and impairment as compared with their departed
      neighbors, and had a higher prevalence of depression and suicide risk at the time
      of enrollment. DISCUSSION: Survivors who come to live in a transitional community
      following a disaster are heterogeneous. Remaining survivors were apparently more
      vulnerable and had a lower capacity to seek work and return to a more self
      sustaining life outside the transitional community. Such vulnerable survivors
      require distinctive strategies for making a successful return to independent
      living.

PMID- 23857816
TI  - Adjunctive antidepressant prescriptions for hospitalized patients with
      schizophrenia in Asia (2001-2009).
AB  - INTRODUCTION: Little is known about the prescription patterns of adjunctive
      antidepressants in Asian schizophrenia patients. This study aimed to examine
      trends in the use of antidepressants and their demographic and clinical
      correlates in the treatment of schizophrenia in Asia between 2001 and 2009.
      METHODS: A total of 6,761 hospitalized schizophrenia patients in nine Asian
      countries and territories were examined: 2,399 in 2001, 2,136 in 2004 and 2,226
      in 2009. Patients' socio-demographic and clinical characteristics and
      prescriptions of psychotropic drugs were recorded using a standardized protocol
      and data collection procedure. RESULTS: The proportion of antidepressant
      prescription was 6.8% in the whole sample; 5.3% in 2001, 6.5% in 2004 and 8.7% in
      2009. There were wide inter-country variations at each survey ranging from 0.9%
      in Hong Kong to 15.3% in Singapore in 2001; from 1.9% in Korea to 15.4% in
      Singapore in 2004; and from 2.7% in Japan to 22.0% in Singapore in 2009. Multiple
      logistic regression analysis of the whole sample revealed that patients on
      antidepressants were younger, more likely to receive benzodiazepines and have
      significant extrapyramidal side-effects and less likely to have significant
      positive symptoms. DISCUSSION: Unlike findings in Western countries, adjunctive
      antidepressant prescription for schizophrenia was not common in Asia. The
      frequency of antidepressant prescription varied among countries and territories,
      suggesting that a host of clinical and socio-cultural factors played a role in
      determining antidepressant use in Asia.

PMID- 23857817
TI  - Low-dose escitalopram-associated hyponatremia.

PMID- 23857818
TI  - Theory of mind in schizophrenia: correlation with clinical symptomatology,
      emotional recognition and ward behavior.
AB  - INTRODUCTION: Several studies have suggested the presence of a theory of mind
      (ToM) deficit in schizophrenic disorders. This study examined the relationship of
      emotion recognition, theory of mind, and ward behavior in patients with
      schizophrenia. METHODS: Fifty-five patients with chronic schizophrenia completed
      measures of emotion recognition, ToM, intelligence, Positive and Negative
      Syndrome Scale (PANSS) and Nurse's Observation Scale for Inpatient Evaluation
      (NOSIE). RESULTS: Theory of mind sum score correlated significantly with IQ,
      emotion recognition, and ward behavior. Ward behavior was linked to the duration
      of the illness, and even more so to theory of mind deficits. Theory of mind
      contributed a significant proportion of the amount of variance to explain social
      behavior on the ward. DISCUSSION: Considering our study results, impaired theory
      of mind contributes significantly to the understanding of social competence in
      patients with schizophrenia.

PMID- 23857819
TI  - Total synthesis of indotertine A and drimentines A, F, and G.

PMID- 23857820
TI  - Malignant deep brain stimulation-withdrawal syndrome in a patient with
      Parkinson's disease.

PMID- 23857821
TI  - First report of a novel polymer-free dual-drug eluting stent in de novo coronary
      artery disease: results of the first in human BICARE trial.
AB  - BACKGROUND: Persistence of stent polymer coating has been associated with
      incomplete endothelialization, expansive vessel remodeling, neoatherosclerosis,
      and delayed healing associated with inflammation that may contribute to late
      adverse events. METHODS: The BICARE (Lepu Medical, Beijing, China) stent is a
      novel polymer-free, nanotechnology-based stent eluting sirolimus and probucol. As
      a first in human feasibility study, patients with a single de novo native
      coronary stenosis <30 mm in length and with reference vessel diameter from 2.5 to
      4.0 mm underwent revascularization with the BICARE stent. The primary endpoint of
      target lesion failure (TLF) was assessed at 30 days. Secondary endpoints included
      in-stent late lumen loss and proportion of uncovered or malapposed stent struts
      by optical coherence tomography at 4-month angiographic surveillance. RESULTS:
      Among 32 consecutive patients (age, 55.7 +/- 8.7 years; men, 62.5%; diabetes,
      18.8%), the average baseline reference vessel diameter and lesion length were
      2.85 +/- 0.48 mm and 15.0 +/- 5.6 mm, respectively. At 30 days there was no
      occurrence of TLF. At 4 months (angiographic follow-up, N=32), angiographic in
      stent late loss was 0.14 +/- 0.19 mm, and the in-stent binary restenosis rate was
      3.1%. Complete strut coverage was 98.2% with 0.2% malapposition among 16,751
      analyzed struts. At 18 months, TLF occurred in 3 (9.4%) patients related to
      repeat revascularization with no adverse safety events identified. CONCLUSIONS:
      The preliminary feasibility and safety of a polymer-free, dual-drug eluting stent
      are demonstrated by absence of early adverse safety events and favorable
      angiographic suppression of neointimal hyperplasia. Stent imaging suggests
      favorable healing with extensive stent strut coverage and very low malapposition.
      These findings further inform comparison with biopermanent polymer DES.

PMID- 23857822
TI  - Synthesis, structure, and theoretical study of trifluoromethyl derivatives of
      C84(23) fullerene.
AB  - Trifluoromethylation of a higher fullerene mixture with CF3I was performed in
      ampoules at 550  degrees C. HPLC separation followed by crystal growth and X-ray
      diffraction study resulted in the structure elucidation of nine CF3 derivatives
      of D2d-C84 (isomer 23). The molecular structures of C84(23)(CF3)4, C84(23)(CF3)8,
      C84(23)(CF3)10, C84(23)(CF3)12, two isomers of C84(23)(CF3)14, two isomers of
      C84(23)(CF3)16, and C84(23)(CF3)18 were discussed in terms of their addition
      patterns and the relative formation energies. Extensive theoretical DFT
      calculations were performed to identify the most stable molecular structures. It
      was found that the addition of CF3 groups to the C84(23) fullerene is governed by
      two main rules: no additions in positions of triple hexagon junctions and
      predominantly para additions in C6(CF3)2 hexagons on the fullerene cage. The only
      exception with an isolated CF3 group in C84(23)(CF3)12 is discussed in more
      detail.

PMID- 23857823
TI  - Database of normal Japanese gray matter volumes in the default mode network.
AB  - PURPOSE: To show the gray matter volumes in the default mode network (DMN) using
      the atlas-based method and to evaluate age-related volume change in the DMN
      region. Estimation of gray matter volumes is interesting research because
      previous reports showed an association with gray matter volume (GMV) and
      diseases. MATERIALS AND METHODS: We focused on five nodes of the DMN (posterior
      cingulate, precuneus, lateral temporal cortex [LTC], medial prefrontal cortex,
      and inferior parietal lobule). In all, 1122 healthy adults were included in the
      present study. T1-weighted magnetic resonance (MR) images were obtained using a
      3T-MR scanner. To investigate GMV in the DMN, segmented gray matter images were
      measured by the atlas-based method, using Statistical Parametric Mapping 5.
      Volumes were expressed using three different methods: region of interest (ROI)
      volume (mL), the volume itself; ROI-TIV (%), as a percentage of total
      intracranial volume (individual difference of head size is corrected); and ROI
      GMV (%), as a percentage of gray matter volume (individual difference of atrophy
      speed for aging is corrected). RESULTS: Negative correlations between measurement
      values on ROI and age were observed in all five ROIs of the DMN region by two
      measures of volume (ROI-volume (mL) and ROI-TIV (%)), in both genders. In
      contrast, positive correlations between measurement values on ROI and age were
      observed in the posterior cingulate and LTC with ROI-GMV (%), in both genders.
      CONCLUSION: The present study is the first report about volume change in the DMN
      that includes age-related effects.

PMID- 23857824
TI  - Comparison of suicide attempts in schizophrenia and major depressive disorder: an
      exploratory study.
AB  - INTRODUCTION: Schizophrenia and major depressive disorder (MDD) are among the
      most common psychiatric diagnoses associated with suicide. There is a dearth of
      published research systematically comparing suicidal behavior in schizophrenia
      and MDD. The present study aimed to compare suicide attempts in schizophrenia and
      MDD. METHODS: In this hospital-based, cross-sectional study, 50 outpatients each
      of schizophrenia and MDD were evaluated for their sociodemographic
      characteristics. In subjects with a history of suicide attempt(s), additional
      information related to the attempt(s) was obtained. Suicide Intent Scale (SIS)
      was used to assess the suicidal intent and Mini International Neuropsychiatric
      Interview (MINI) was used to measure the current suicidal risk. RESULTS: Thirty
      four percent and 44% of patients with schizophrenia and MDD, respectively,
      attempted suicide. The attempters in schizophrenia compared to those in MDD were
      younger and more likely to be single (unmarried, separated or divorced). Suicidal
      intent was stronger in schizophrenia, while the attempters with MDD were more
      often preoccupied with a death wish and reported that stressful life events
      influenced the attempt. There were no differences in the attempt methods of the
      two groups. Current suicidal risk was higher in attempters compared to the non
      attempters in schizophrenia as well as MDD. DISCUSSION: Suicide attempts in
      schizophrenia and MDD have similar features, with quite a few notable
      differences, which have been discussed at length in the present paper.

PMID- 23857828
TI  - Welcome from the editors of Asia Pacific Psychiatry.

PMID- 23857826
TI  - Health-related quality of life and symptom severity in Chinese patients with
      major depressive disorder.
AB  - INTRODUCTION: Patients suffering from major depressive disorder (MDD) have been
      reported to have substantial long-lasting limitations in multiple domains of
      health-related quality of life (HRQoL). The thoughtful assessment of HRQoL and
      the impact of treatment response on HRQoL are emerging as important issues in the
      care of patients with major depressive disorder. METHODS: One hundred and three
      patients meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)
      criteria for MDD took fluoxetine (20 mg/d) for 6 weeks and were assessed by the
      Short Form 36 Health Survey (SF-36), the 17-item Hamilton Depression Rating (HAMD
      17) and the Clinical Global Impression (CGI) scales. Relationships between SF-36
      scores and depressive symptom severity and early change of these symptoms were
      tested. RESULTS: SF-36 component scores at week 6 were higher than those at
      baseline (all P <= 0.0058). Scores for general health were significantly higher
      in responders than non-responders (P = 0.0009). The overall HAMD-17 and CGI
      scores at 2- and 6-week follow-up were significantly lower than those at baseline
      (P <= 0.0001). Higher scores for anxiety/somatization were significantly
      associated with poorer SF-36 scores at baseline (P = 0.0001); role-physical
      scores at week 6 were positively correlated with reduction rate of
      anxiety/somatization in 2-week follow-up (P = 0.0002). DISCUSSION: Depressive
      symptom severity was associated with HRQoL in patients with MDD. HRQoL may vary
      with severity of depression and/or anxiety-somatization at baseline.

PMID- 23857825
TI  - Endothelial cell motility, coordination and pattern formation during
      vasculogenesis.
AB  - How vascular networks assemble is a fundamental problem of developmental biology
      that also has medical importance. To explain the organizational principles behind
      vascular patterning, we must understand how can tissue level structures be
      controlled through cell behavior patterns like motility and adhesion that, in
      turn, are determined by biochemical signal transduction processes? We discuss the
      various ideas that have been proposed as mechanisms for vascular network
      assembly: cell motility guided by extracellular matrix alignment (contact
      guidance), chemotaxis guided by paracrine and autocrine morphogens, and
      multicellular sprouting guided by cell-cell contacts. All of these processes
      yield emergent patterns, thus endothelial cells can form an interconnected
      structure autonomously, without guidance from an external pre-pattern.

PMID- 23857829
TI  - Perspectives in Malaysian psychiatry.

PMID- 23857830
TI  - Physical health of patients with bipolar disorder.

PMID- 23857831
TI  - Risk factors for depression and anxiety among pregnant women in Hospital Tuanku
      Bainun, Ipoh, Malaysia.
AB  - INTRODUCTION: Anxiety and depression are prevalent during pregnancy. Estimates of
      the prevalence of anxiety and depression during pregnancy vary according to the
      criteria used, variable methodologies and population characteristics. METHODS: A
      cross-sectional survey design was used. A total of 175 antenatal mothers
      participated. Their socio-demographic and obstetric histories were recorded. The
      Hospital Anxiety and Depression Scale (HADS) and Mini International
      Neuropsychiatric Interview (M.I.N.I.) were used. RESULTS: The prevalence of
      anxiety and depression disorders among antenatal mothers using diagnostic
      clinical interview were 9.1% and 8.6%, respectively. Factors associated with
      antenatal anxiety were marital status (being unmarried), positive history of
      mental illness, gestational age (<20 weeks), unplanned pregnancy and depressive
      comorbidity. However, only gestational age of less than 20 weeks and depressive
      disorder remained significant factors in the multivariate analysis. DISCUSSION:
      The prevalence rate of antenatal depression detected by HADS screening was
      comparable to the rate from diagnostic interview, but there was a slight
      overestimation for antenatal anxiety. Nonetheless, HADS as a screening tool
      offers a practical solution for detecting these two conditions in a busy
      antenatal clinic or a large epidemiological survey. In view of the deleterious
      effects of antenatal anxiety and depression on mothers and children, these two
      conditions should be screened and managed appropriately.

PMID- 23857832
TI  - Sexual desire disorder in female healthcare personnel in Malaysia.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence and risk
      factors for female sexual desire disorder (FSDD) among healthcare personnel at
      selected healthcare facilities in Malaysia. METHODS: Two hundred and one female
      healthcare workers from three large tertiary hospitals were selected by
      stratified random sampling to participate in this cross-sectional study.
      Validated questionnaires were used to assess depression, anxiety, and sexual
      function in women and erectile dysfunction (ED) in their partners. RESULTS: The
      prevalence of FSDD was 18.9%. Women with low sexual desire were more likely to
      have higher educational attainment (OR = 3.06; 95% CI; 1.22-7.66), lower
      frequency of sexual intercourse (OR = 12.81; 95% CI; 4.43-37.83), two or more
      children (OR = 3.05; 95% CI; 1.02-9.09), duration of marriage of 20 years or more
      (OR = 2.62; 95% CI; 1.27-5.40), and a spouse with ED (OR = 2.86; 95% CI; 1.08
      7.56). DISCUSSION: FSDD is common among female healthcare personnel in Malaysia,
      affecting nearly one in five women. The implication of low sexual desire is
      important in terms of contributing to a meaningful sexual relationship, and
      indirectly affects the quality of life of the healthcare personnel.

PMID- 23857833
TI  - Risk and associated factors of female sexual orgasmic disorder in women with
      hypertension in Malaysia.
AB  - INTRODUCTION: The objective of this study was to examine the risk of female
      sexual orgasmic disorder among a group of women with hypertension in Malaysia.
      The associated factors were also examined. METHODS: This cross-sectional study
      involved 348 hypertensive women attending the primary care or hypertension clinic
      in a teaching hospital in Malaysia. Female sexual orgasmic disorder was assessed
      using the Orgasmic subscale of the Malay Version of the Female Sexual Function
      Index (MVFSFI). Basic socio-demographic data of the subjects was collected using
      a predesigned questionnaire. Medical records were reviewed to gather patients'
      medical information. RESULTS: The risk of female sexual orgasmic disorder among
      hypertensive women was 14.1%. Univariate analysis found that older age, longer
      duration of marriage, lower educational level, and menopause were associated with
      higher risk of female sexual orgasmic disorder. These factors were not
      significant in multivariate analysis. DISCUSSION: The risk of female sexual
      orgasmic disorder was relatively low in Malaysian women with hypertension. No
      risk factors were associated with female sexual orgasmic disorder in the current
      study.

PMID- 23857834
TI  - Externalizing and internalizing syndromes in relation to school truancy among
      adolescents in high-risk urban schools.
AB  - INTRODUCTION: To examine the relationship between externalizing/internalizing
      syndromes and school truancy among Form Four (10th grade) students attending
      "high-risk" schools in Kuala Lumpur. METHODS: This is a cross-sectional study
      conducted upon 16-year-old adolescents attending three high-risk schools in Kuala
      Lumpur. A total of 373 students completed self-administered questionnaires on the
      sociodemographic variables and externalizing/internalizing syndromes. The number
      of truant-days per student during the study period was obtained from the school
      records. RESULTS: The mean internalizing score, externalizing score and total
      problem score of those who were truant were found to be significantly higher (P <
      0.05) than those who were non-truant. Multiple logistic regressions showed
      externalizing syndrome (odds ratio [OR] = 1.044; confidence interval [CI] = 1.012
      1.078, P = 0.018) significantly predicts truancy but not the internalizing
      syndrome. Two other psychosocial factors, namely, having divorced parents (OR =
      2.495, CI = 1.058-5.886, P = 0.037) and did not understand or were uncertain of
      the purpose of schooling (OR = 2.621, CI = 1.265-5.433, P = 0.010) were also
      showed to be stronger predictors of truancy compared to
      externalizing/internalizing syndromes. DISCUSSION: Truancy has significant
      association to externalizing syndrome, in addition to other significant
      psychosocial variables like parental and schooling factors. This finding
      indicated the need for comprehensive assessment of students presenting with
      truant behavior, including the identification of associated psychological and
      behavioral problems which highlights the roles of mental health professionals in
      tackling truancy.

PMID- 23857835
TI  - Depression and coping in adults undergoing dialysis for end-stage renal disease.
AB  - INTRODUCTION: Research on depression in local patients with end-stage renal
      disease (ESRD) is sparse. Thus, this study aims to examine the frequency and
      severity of depression among ESRD patients and relate depression with their
      coping skills. METHODS: A cross-sectional study using universal sampling method
      was conducted at several dialysis centers in Kuala Lumpur, Selangor and Johor,
      Malaysia. The Beck Depression Inventory II (BDI-II) and the Brief COPE scale were
      used to measure depression and coping skill, respectively. RESULTS: The study
      involved 274 ESRD patients, comprising of 183 hemodialysis and 91 continuous
      ambulatory peritoneal dialysis patients. The result showed that 21.1% of the
      patients experienced moderate to severe depression. Several components of coping
      skill were associated with depression. However, only two components in the Brief
      COPE (behavioral disengagement and self-blame) were identified as predictors.
      DISCUSSION: This study showed that depression is common in ESRD patients and is
      related to the types of coping skills adopted by patients. Hence, this study
      provides some insight into ESRD patients with depression. Appropriate counseling
      should be given to these patients to empower them to cope with the illness so as
      to enhance their quality of life.

PMID- 23857836
TI  - Association between 5HT2A polymorphism and selective serotonin re-uptake
      inhibitor (SSRI)-induced sexual desire disorder (SDD) among Malaysian women.
AB  - INTRODUCTION: SSRIs are known for their sexual side-effects with a variable rate
      of sexual dysfunction (SD). 5HT2A (rs6311) single nucleotide polymorphism (SNP)
      was found to have significant association with SD. The purpose of this study was
      to determine the prevalence of female SDD, its clinical correlates and
      association with 5HT2A (rs6311) SNP in patients with major depressive disorder
      (MDD) treated with SSRIs. METHODS: This was a cross-sectional study. We evaluated
      95 female outpatients with MDD treated with SSRIs who were in remission. Outcome
      measures were stratified by the presence or absence of SDD. A buccal swab was
      obtained from each patient and sent for genotyping in the Pharmacogenomics and
      Medical Biotechnology Laboratory of Universiti Malaya. RESULTS: The overall
      prevalence of female SD was 32.6%. The prevalence of female SDD was 62.1%. Those
      with arousal problem, lubrication problem, sexual satisfaction problem, orgasm
      problem and problematic marriage were more likely to have sexual desire disorder.
      The majority of participants who had sexual desire disorder had genotype TT
      (42.4%) but there was no significant association observed. After controlling for
      age, number of children, education level, SSRI type, lubrication problem, orgasm
      problem, satisfaction problem and marital problem, only arousal problem
      significantly enhanced the presence of sexual desire disorder by 8.5 times (odds
      ratio = 8.46, 95% confidence interval = 1.24-57.58; P = 0.018). DISCUSSION: This
      study showed that there was no significant association between SDD and the 5HT2A
      (rs6311) SNP. Arousal problem significantly enhanced the presence of sexual
      desire disorder.

PMID- 23857837
TI  - Phases of female sexual response cycle among Malaysian women with infertility: a
      factor analysis study.
AB  - INTRODUCTION: This cross-sectional study aimed to determine the construct of the
      phases of the female sexual response cycle (SRC) among women attending an
      infertility clinic in a Malaysian tertiary center. METHODS: The sexual response
      phases were measured with a validated Malay version of the Female Sexual Function
      Index (FSFI). The correlation structure of the items of the SRC phases (i.e.
      desire, arousal, orgasm, satisfaction and pain) was determined using principal
      component analysis (PCA), with varimax rotation method. The number of factors
      obtained was decided using Kaiser's criteria. RESULTS: A total of 150 married
      women with a mean age of 32 years participated in this study. Factor loadings
      using PCA with varimax rotation divided the sexual domains into three components.
      The first construct comprised sexual arousal, lubrication and pain (suggesting a
      mechanical component). The second construct were orgasm and sexual satisfaction
      (suggesting a physical achievement). Sexual desire, suggesting a psychological
      component, stood on its own as the third. DISCUSSION: The findings suggest that
      three constructs could be identified and in favor of the Basson model (a non
      linear concept of SRC) for Malaysian women's sexual functioning. Understanding
      this would help clinicians to strategize the treatment approach of sexual
      dysfunction in women with infertility.

PMID- 23857838
TI  - Malignant catatonia secondary to viral meningoencephalitis in a young man with
      bipolar disorder.

PMID- 23857839
TI  - Relationships between social support and depression, and quality of life of the
      elderly in a rural community in Malaysia.
AB  - INTRODUCTION: This study aimed to examine the role of social support and
      depression in predicting the quality of life among the elderly living in a rural
      Federal Land Development Authority (FELDA) community in Malaysia. METHODS: A
      total of 162 elderly settlers of FELDA Sungai Tengi, aged 60 years and above,
      were selected by universal sampling method in this cross-sectional study. Three
      standardized instruments - the 12-item Short Form (SF-12), 15-item Geriatric
      Depression Scale (GDS-15) and Medical Outcome Study Social Support (MOS-Social
      Support) - were used to assess for quality of life, depression and social
      support. RESULTS: Quality of life of the elderly people in this community was
      high, especially in terms of physical components as compared to mental
      components. The mean scores for emotional role in the SF-12 was relatively the
      highest (90.74 +/- 21.59) with social functioning being the lowest (30.35 +/-
      22.29). The results also showed that the mean value was higher for physical
      component summary (74.40) as compared to mental component summary (51.51).
      Approximately 23.5% suffered mild depression and only 2.5% had severe depression.
      DISCUSSION: This study showed that the elderly FELDA settlers have a high quality
      of life, mainly on the physical components of life and low rate of severe
      depression, a positive indicator of their psychological well-being. Social
      support in the form of emotional/informational support, and depression were
      significant factors related to their good quality of life.

PMID- 23857840
TI  - Depression in male patients on methadone maintenance therapy.
AB  - INTRODUCTION: Depression is one of the most common psychiatric conditions in men.
      The aim of the study was to determine the depressive symptoms and associated
      factors among men on methadone maintenance therapy (MMT). METHODS: A cross
      sectional study was conducted involving 108 subjects who attended the Drug Clinic
      at Hospital Kuala Lumpur. The instruments used include the Structured Clinical
      Interview for Diagnostic and Statistical Manual, Fourth Edition Axis-I Disorder,
      Beck Depression Inventory and the 15-item International Index of Erectile
      Function. RESULTS: The rate of depression was 44.4%. There were significant
      associations between Malay ethnicity, secondary education level and concurrent
      illicit cannabis use with depression (P < 0.05). However, there was no
      significant associations between depression and erectile dysfunction (P = 0.379).
      DISCUSSION: Even though depression is common among men on MMT, it is often missed
      by the treating doctors. It is important to make the treating doctors aware that
      depression is a serious clinical condition that has a profound impact on the
      individual and compliance to treatment.

PMID- 23857841
TI  - Physician, heal thyself: the paradox of anxiety amongst house officers and work
      in a teaching hospital.
AB  - INTRODUCTION: Anxiety among house officers may impair functioning and health care
      delivery. This study aimed to determine the association between anxiety among
      house officers at Universiti Kebangsaan Malaysia Medical Center, sociodemographic
      and work-related factors. METHODS: A cross-sectional study using the self-rated
      and validated Malay Depressive Anxiety and Stress Scale 21, the General Stressor
      Questionnaire and a sociodemographic questionnaire. RESULTS: Of the 89 house
      officers, 60.7% were anxious. Multivariate logistic analysis showed work-related
      challenges, performance pressure (odds ratio [OR] = 9.000, 95% confidence
      interval [CI] = 1.812-44.705), poor relationship with supervisors (OR = 5.212,
      95% CI = 2.033-3.365), poor relationship with colleagues (OR = 4.642, 95% CI =
      1.816-11.866), bureaucratic constraints (OR = 3.810, 95% CI = 1.541-9.415) and
      poor job prospects (OR = 3.745, 95% CI = 1.505-9.321) strongly associated with
      anxiety. Family-related stressors were less significant (OR = 1.800, 95% CI =
      0.760-4.266) unless they were work related (work-family conflicts [OR = 8.253,
      95% CI = 2.652-25.684]). DISCUSSION: Almost two-thirds of this cohort reported
      work-related anxiety symptoms. Administrators need to address these mental health
      needs early. The subsequent improvement in communication skills, conflict
      resolution and anxiety reduction will result in short- and long-term benefits
      towards the young doctors's mental health. The cascading impact on these
      individuals, thus empowered, will be good work-life balance, improved patient
      care and safety, a satisfying medical career whilst contributing maximally to the
      country's health care.

PMID- 23857843
TI  - Neurosyphilis and psychosis.
AB  - Neurosyphilis may presents with a range of psychiatric symptoms. This report
      illustrates a case of neurosyphilis in a man who presented with psychosis and
      cognitive dysfunction. Clinical findings and investigations done in the present
      case showed positive results for syphilis. Reduction of symptoms was noted after
      treatment with antibiotic. This case further highlights the importance of having
      high index of suspicion for neurosyphilis in patients presenting with psychiatric
      symptoms. 

PMID- 23857842
TI  - Stressors in secondary boarding school students: association with stress, anxiety
      and depressive symptoms.
AB  - INTRODUCTION: Chronic stress in adolescents may cause physical, mental and
      emotional health issues which lead to poor outcomes if left untreated. The
      present study aimed to determine the prevalence of depression, anxiety and
      stress, and their association with stressors. METHODS: A cross-sectional study
      was conducted among 350 students in a selected boarding school. Two validated
      Malay version questionnaires were used as instruments, which comprised the 21
      item Depression, Anxiety and Stress Scale to assess depression, anxiety and
      stress level, and Soalselidik Stressor Sekolah Menengah to assess stressors.
      RESULTS: The prevalence of depression, anxiety and stress were 39.7%, 67.1% and
      44.9%, respectively. The highest mean score was 2.3 (+/-0.80) for the academic
      related stressor. All stressors (academic, interpersonal, intrapersonal, teacher,
      learning/teaching and social group) had significant association with depression,
      anxiety and stress (P < 0.001). Multiple regression showed that both the
      intrapersonal-related stressor and learning/teaching-related stressor were 2.8-
      and 2.0-times more likely (adjusted odds ratio [OR] = 2.8 [P < 0.001] and OR =
      2.0 [P = 0.002], respectively) to cause depressive symptoms. On the other hand,
      the interpersonal-related stressor was 2.9-times more likely (adjusted OR = 2.9,
      P < 0.001) to cause anxiety. The learning/teaching-related and intrapersonal
      related stressors were 2.7- and 2.5-times more likely to develop stress (adjusted
      OR = 2.7 [P < 0.001] and OR = 2.5 [P = 0.001], respectively). DISCUSSION: The
      possibility of introducing screening for mental health problems among boarding
      school students needs to be considered and investigated. Addressing the possible
      stressors and employing healthy coping may help in reducing negative emotional
      outcomes in these students.

PMID- 23857844
TI  - Young female survivors of sexual abuse in Malaysia and depression: what factors
      are associated with better outcome?
AB  - INTRODUCTION: Research in the field of child sexual abuse is lacking in Malaysia.
      The aims of this study are to identify the association between sociodemographic
      factors and depression among sexually abused females. METHODS: A cross-sectional
      study was conducted among 51 young sexually abused female attendees at the
      Suspected Child Abuse and Neglect (SCAN) clinic of Hospital Kuala Lumpur, a
      tertiary referral centre. Upon obtaining informed consent from participant and
      guardian, participants were screened for depression using the Strength and
      Difficulty Questionnaire (SDQ) and interviewed using the Schedule for Affective
      Disorders and Schizophrenia for School Aged Children (K-SADS) for depressive
      disorders and K-SADS-PL (Present and Lifetime version) to diagnose depression.
      Sociodemographic data and details of the abuse were also obtained. RESULTS: Of
      the survivors, 33.3% were depressed. Univariate analysis showed significant
      association between legal guardianship, living environment and duration of abuse
      with depression, however, multivariate analyses later showed that the sole
      predictor for depression was living environment. Respondents who lived with
      others were 23-times more likely to be depressed as compared to those who lived
      with their parents. DISCUSSION: Depression is common among young survivors of
      sexual abuse. Those who lived with parents appeared to have a better outcome.
      Thus, further research to explore possible protective factors associated with
      living with parents is vital. This will help clinicians develop strategies to
      empower parents and families help these young survivors get back on track with
      their lives despite the abuse.

PMID- 23857845
TI  - Knowledge and attitude on sex among medical students of a Malaysian university: a
      comparison study.
AB  - INTRODUCTION: The objective of this study was to determine the relationship
      between clinical/socio-demographic factors with knowledge and attitude on sex
      among medical students of the National University of Malaysia (UKM). METHODS: A
      cross-sectional study assessing 452 students using a self-administered
      questionnaire of knowledge and attitude was performed and had a response rate of
      80%. RESULTS: The majority of respondents were Malays (56%), females (57.5%),
      lived in urban areas (66.4%), had a median family income of RM3000 and perceived
      themselves as moderately religious (60%). The overall score on knowledge about
      sex was 21.7 of 35 (a higher score indicates better knowledge about sex). It was
      noted that 73.2% of students felt that they did not receive adequate training in
      medical school to deal with patients' sexuality and sexual problems, while 51.5%
      felt uncomfortable talking to patients about these issues. Students in the
      clinical year were more knowledgeable than those in pre-clinical years (22.67
      versus 20.71, P < 0.001). No significant differences were found in terms of their
      backgrounds, such as being from urban or rural areas (P = 0.349) and between
      genders (P = 0.286). Only 54.9% of students had a satisfactory level of knowledge
      on sex (>22 marks [median score]). DISCUSSION: The students' attitude on sex was
      considered conservative as the majority of them disagreed on premarital sex,
      masturbation, abortion, homosexuality and oral sex. Gender and religiosity have a
      large influence on attitudes on controversial sexual issues, whereas clinical
      status plays a small role. Knowledge on sex among UKM medical students is
      inadequate and their attitudes on sex are considered conservative. Integration of
      sexual medicine and health modules in the medical curriculum is crucial for
      students to more effectively address patients' sexual problems and promote non
      judgmental attitudes towards patients.

PMID- 23857846
TI  - Quality of life in Malaysian colorectal cancer patients.
AB  - INTRODUCTION: The rapidly increasing of incidence colorectal cancer (CRC) in
      Malaysia and the introduction of new treatments that prolong survival advocating
      treatment outcome measures such as patients' quality of life (QOL) are evaluated
      in this study. The study aims to determine QOL in CRC patients according to
      cancer stage and age. METHODS: A cross-sectional study was performed from June to
      December 2011 at four public tertiary hospitals. The European Organization for
      Research and Treatment in Cancer (EORTC) Quality of Life Questionnaire Core-30
      (EORTC QLQ C-30) questionnaire was used through face-to-face interview and the
      medical records of 160 respondents were reviewed. RESULTS: The mean age of
      respondents was 58.47 +/- 12.04 years with 57.5% of respondents being male and
      42.5% female. The majority of respondents were in CRC stages III and IV. Median
      global health status (GHS) score was 83.33 (IQR 16.67). Sikhs and Indians had a
      higher median GHS score compared to other ethnicities (Kruskal-Wallis, chi(2)  =
      12.12, p = 0.007). Emotional, cognitive and social functions were higher in
      respondents with earlier stage of disease (Kruskal-Wallis, chi2 = 6.06, 6.36,
      10.58, p = 0.048, 0.042, 0.005). Median pain, dyspnea, diarrhea and financial
      implication scores were significantly higher in advanced stage of disease
      (Kruskal-Wallis, chi(2)  = 9.31, 6.26,6.77, 7.28, p = 0.010, 0.044,0.034,0.026).
      Median diarrhea score (p = 0.012) was significantly different between age groups.
      DISCUSSION: Emotional, cognitive and social functions deteriorate with advanced
      stage of disease. Patients with advanced stage disease experience more pain,
      dyspnea, diarrhea and financial implications. A systematic screening program to
      detect cases as early as possible is essential nationwide.

PMID- 23857847
TI  - Reliability and validity of the Malay version of Attitudes toward Lesbians and
      Gay Men (MVATL/MVATG): a study on a group of medical students in Malaysia.
AB  - INTRODUCTION: This study aims to examine the validity and reliability of the
      Malay version of Attitudes toward Lesbians and Gay Men (MVATL/MVATG) among a
      group of medical students in Malaysia. METHODS: It is a cross-sectional study of
      173 medical students in the Faculty of Medicine, University of Kuala Lumpur,
      Malaysia. The participants were given the MVATL/MVATG, Index of Attitudes toward
      Homosexuals (IATH), Homosexuality Attitude Scale (HAS) and the English version of
      Attitude toward Lesbians and Gay Men. Two weeks later, these students were given
      the MVATLG again. RESULTS: Significant correlation was found between the
      individual scores of MVATL and MVATG with IATH and HAS in the results. The scale
      was able to differentiate Muslim and Non-Muslim subjects. The internal
      consistency (Cronbach's alpha) of both the MVATL and MVATG were good, at 0.76 and
      0.82, respectively. The parallel form reliability (Pearson's correlation) of
      MVATL was 0.0.73 and 0.74 for MVATG. The test-retest reliability of MVATL/MVATG
      was good (Intraclass correlation coefficient, ICC = 0.67 for MVATL and 0.60 for
      MVATG). DISCUSSION: The MVATLG demonstrated good psychometric properties in
      measuring attitudes toward homosexuality among a group of medical students in
      Malaysia and it could be used as a simple instrument on young educated Malaysian
      adults.

PMID- 23857848
TI  - Sexual abuse and substance abuse increase risk of suicidal behavior in Malaysian
      youth.
AB  - INTRODUCTION: The aim of this study was to determine the association between
      sexual abuse, substance abuse and socio-demographic factors with suicidal
      ideation (SI), plans (SP) and deliberate self-harm (DSH) and propose steps to
      prevent youth suicidal behavior. METHODS: This was a cross-sectional study of
      6786 adolescents aged 17-18 years, selected randomly from all Malaysian
      adolescents to undergo compulsory youth camps located in Selangor, Malaysia (2008
      2009). Participants were assessed using self-administered questionnaires
      developed to reflect the local cultural setting. However, only 4581 subjects were
      analyzed after excluding incomplete data. RESULTS: The rates of SI, SP and DSH
      were 7.6%, 3.2% and 6.3%, respectively. The multivariable-adjusted odds ratio
      showed that sexual abuse was associated with SI 1.99 (95% CI: 1.56-2.55), SP 1.57
      (95% CI: 1.09-2.27) and DSH 2.26 (95% CI: 1.75-2.94); illicit drug use was
      associated with SI 4.05 (95% CI: 2.14-7.67), SP 2.62 (95% CI: 1.05-6.53) and DSH
      2.06, (95% CI: 1.05-4.04); for alcohol use DSH was 1.34 (95% CI: 1.00-1.79).
      Being female was associated with all suicidal behaviors: SI 2.51 (95% CI: 1.91
      3.30), SP 2.07 (95% CI: 1.39-3.08) and DSH 1.59 (95% CI: 1.19-2.11). DISCUSSION:
      Given the well-founded concern of increasing risk of suicidal behavior among
      youth, preventive efforts should adopt a more comprehensive approach in dealing
      with sexual abuse and substance abuse, and their sequelae, especially in girls.

PMID- 23857849
TI  - Hospital-based community psychiatric service for patients with schizophrenia in
      Kuala Lumpur: a 1-year follow-up study of re-hospitalization.
AB  - INTRODUCTION: Hospital-based community psychiatric service (HCPS) is a developing
      intervention in Malaysia targeted for patients with severe mental illnesses
      (SMIs). Its effectiveness had not been systematically measured. This study aimed
      to assess the outcome of HCPS with respect to re-hospitalization and factors
      associated with low re-hospitalization among patients with schizophrenia in the
      metropolitan city of Kuala Lumpur. METHODS: A naturalistic and retrospective
      cohort study was conducted using within-subject pre-post design on 155 patients
      with schizophrenia who received HCPS in Hospital Kuala Lumpur (HKL). The
      selection was made by simple random sampling. The hospital admission profiles
      were obtained from clinical records. The socio-demographic and relevant clinical
      data were also assessed through clinical interviews. RESULTS: One hundred and
      forty (90%) of 155 respondents had low rate of hospital admission with
      significant reduction of being hospitalized within 1 year after receiving HCPS (p
      < 0.001). Having good social support was significantly associated with lower rate
      of rehospitalization (p = 0.001). DISCUSSION: The study revealed the
      effectiveness of HCPS in terms of reducing rates of hospital admission among
      patients with schizophrenia in Malaysia. The finding may be used as an evidence
      to develop the service further in other hospitals. However, the finding needs to
      be replicated through studies with better design involving more psychiatric
      centres.

PMID- 23857850
TI  - Loneliness and depression among the elderly in an agricultural settlement:
      mediating effects of social support.
AB  - INTRODUCTION: Loneliness has long been known to have strong association with
      depression. The relationship between loneliness and depression, however, has been
      associated with other risk factors including social support. The aim of this
      paper is to describe the role of social support in the association between
      loneliness and depression. METHODS: This cross-sectional study examined the
      mediating effects of social support among 161 community-based elderly in
      agricultural settlement of a rural area in Sungai Tengi, Malaysia. Subjects were
      investigated with De Jong Gierveld Loneliness Scale, Geriatric Depression Scale
      and Medical Outcome Survey Social Support Survey. Data were analyzed using
      Pearson correlation, linear and hierarchical regression. RESULTS: Results
      indicated that social support partially mediated the relationship between
      loneliness and depression. DISCUSSION: This suggests that social support affects
      the linear association between loneliness and depression in the elderly.

PMID- 23857851
TI  - A hexanuclear gold cluster supported by three-center-two-electron bonds and
      aurophilic interactions.

PMID- 23857852
TI  - Commentary.

PMID- 23857853
TI  - Canadian medical image app number one in the US.

PMID- 23857854
TI  - Rotavirus vaccine in India faces controversy.

PMID- 23857856
TI  - Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results
      guided transfusion in patients with severe trauma: a randomized feasibility
      trial.
AB  - BACKGROUND: Hemorrhage coupled with coagulopathy remains the leading cause of
      preventable in-hospital deaths among trauma patients. Use of a transfusion
      protocol with a predefined ratio of 1:1:1 (1 each of red blood cells [RBC],
      frozen plasma [FP] and platelets) has been associated with improved survival in
      retrospective studies in military and civilian settings, but such a protocol has
      its challenges and may increase the risk of respiratory complications. We
      conducted a randomized controlled trial to assess the feasibility of a 1:1:1
      transfusion protocol and its effect on mortality and complications among patients
      with severe trauma. METHODS: We included 78 patients seen in a tertiary trauma
      centre between July 2009 and October 2011 who had hypotension and bleeding and
      were expected to need massive transfusion (>= 10 RBC units in 24 h). We randomly
      assigned them to either the fixed-ratio (1:1:1) transfusion protocol (n = 40) or
      to a laboratory-results-guided transfusion protocol (control; n = 38). The
      primary outcome, feasibility, was assessed in terms of blood product ratios and
      plasma wastage. Safety was measured based on 28-day mortality and survival free
      of acute respiratory distress syndrome. RESULTS: Overall, a transfusion ratio of
      1:1:1 was achieved in 57% (21/37) of patients in the fixed-ratio group, as
      compared with 6% (2/32) in the control group. A ratio of 1:1 (RBC:FP) was
      achieved in 73% (27/37) in the fixed-ratio group and 22% (7/32) in the control
      group. Plasma wastage was higher with the intervention protocol (22% [86/390] of
      FP units v. 10% [30/289] in the control group). The 28-day mortality and number
      of days free of acute respiratory distress syndrome were statistically similar
      between the groups. INTERPRETATION: The fixed-ratio transfusion protocol was
      feasible in our study, but it was associated with increased plasma wastage.
      Larger randomized trials are needed to evaluate the efficacy of such a protocol
      in trauma care. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00945542.

PMID- 23857858
TI  - Grand Challenges awards 102 global health grants.

PMID- 23857859
TI  - Managing polypharmacy in a 77-year-old woman with multiple prescribers.

PMID- 23857860
TI  - Just ask: discussing goals of care with patients in hospital with serious
      illness.

PMID- 23857862
TI  - The end of resident all-nighters?

PMID- 23857861
TI  - Oropharyngeal tularemia.

PMID- 23857863
TI  - International alliance to share genomic data.

PMID- 23857865
TI  - Pd(II)-catalyzed spiroketalization of ketoallylic diols.
AB  - A high-yielding stereoselective method for forming spiroketals from simple
      ketoallylic diols is reported. Employing catalytic [PdCl2(MeCN)2] in THF at 0 
      degrees C, these dehydrative cyclization reactions require only mild conditions
      to produce vinyl-substituted spiroketals in high yields after brief reaction
      times with water as the only byproduct. Using this method, the stereochemical
      information embedded at the nucleophile is transmitted "down-the-chain" and
      efficiently sets the stereochemistry at both the anomeric carbon atom and the
      newly formed allylic stereocenter.

PMID- 23857864
TI  - Design and methods of a postmarketing pharmacoepidemiology study assessing long
      term safety of Prolia(r) (denosumab) for the treatment of postmenopausal
      osteoporosis.
AB  - PURPOSE: To describe the rationale and methods for a prospective, open-cohort
      study assessing the long-term safety of Prolia((r)) for treatment of
      postmenopausal osteoporosis (PMO) in postmarketing settings. METHODS: Data will
      be derived from United States Medicare, United Healthcare, and Nordic (Denmark,
      Sweden, Norway) national registries. Observation will begin on the date of first
      Prolia((r)) regulatory approval (May 26, 2010) and continue for 10 years. Women
      with PMO will be identified by postmenopausal age, osteoporosis diagnosis,
      osteoporotic fracture, or osteoporosis treatment. Exposure to Prolia((r)) and
      bisphosphonates will be updated during follow-up; exposure cohorts will be
      defined based on patient-years during which patients are on- or post-treatment.
      Nine adverse events (AEs) will be assessed based on diagnosis codes:
      osteonecrosis of the jaw (ONJ), atypical femoral fracture (AFF), fracture healing
      complications, hypocalcemia, infection, dermatologic AEs, acute pancreatitis,
      hypersensitivity, and new primary malignancy. Medical review will confirm
      selected potential cases of ONJ and AFF. Incidence rates (IRs) of AEs will be
      described overall and for exposure cohorts; multivariate Cox proportional hazard
      regression models will compare IRs of AEs across exposure cohorts. Utilization
      patterns of Prolia((r)) for approved, and unapproved indications will be
      described. CONCLUSION: This study is based on comprehensive preliminary research
      and considers methodological challenges specific to the study population. The
      integrated data systems used in this regulatory committed program can serve as a
      powerful data resource to assess diverse and rare AEs over time.

PMID- 23857866
TI  - Quality of life of patients with epilepsy in Malaysia.
AB  - INTRODUCTION: To determine the quality of life of patients with epilepsy and its
      relationship with depression, and the clinical and sociodemographic variables.
      METHODS: This was a cross-sectional study in which a total of 120 epilepsy
      patients were recruited from a neurology outpatient clinic. Sociodemographic and
      clinical variables were recorded. Hospital Anxiety and Depression Scale (HADS)
      and Mini International Neuropsychiatric Interview (M.I.N.I.) were used to screen
      and diagnose for depression, respectively. Quality of Life Inventory of Epilepsy
      (QOLIE-31) was used to assess quality of life. RESULTS: Patients with epilepsy
      with major depression had poorer quality life (36.4 +/- 1.8) compared to those
      without depression (41.7 +/- 3.8, P < 0.001). Depression, having one seizure or
      more per month and having seizures within one month of interview were correlated
      with poorer quality of life, P < 0.001. Multivariate linear regression analyses
      showed that depression and recent seizures predicted having poorer quality of
      life in patients with epilepsy. DISCUSSION: Depression and poor seizure control
      were predictors for poor quality of life in patients with epilepsy. Therefore,
      epilepsy patients should be regularly screened for depression and treatment for
      epilepsy must be optimized to minimize the negative impact of having epilepsy for
      these patients.

PMID- 23857867
TI  - Occurrence of red complex microorganisms and Aggregatibacter
      actinomycetemcomitans in patients with diabetes.
AB  - AIM: The aim of the present study was to analyze the occurrence of Porphyromonas
      gingivalis (P. gingivalis), Tannerella forsythia (T. forsythia), Treponema
      denticola (T. denticola), and Aggregatibacter actinomycetemcomitans (A.
      actinomycetemcomitans) in patients with diabetes. METHODS: Periodontal and
      diabetic parameters and subgingival biofilm samples were obtained from 60
      patients with diabetes and 62 patients without diabetes. By using polymerase
      chain reaction, the prevalence of red complex microorganisms (P. gingivalis, T.
      forsythia, and T. denticola) and A. actinomycetemcomitans were determined.
      Descriptive and non-parametric statistical analyses between groups were performed
      (Kruskal-Wallis, Mann-Whitney U-test, and Fisher's exact test). RESULTS: Patients
      with diabetes presented significantly higher periodontal attachment loss levels
      compared to patients without diabetes. Red complex microorganisms were detected
      in lower frequencies in patients with diabetes. The detection of A.
      actinomycetemcomitans was higher in patients with diabetes and periodontitis
      compared to systemically-healthy patients without periodontitis (P < 0.05). P.
      gingivalis was associated with periodontitis in non-diabetic patients (P < 0.05),
      whereas A. actinomycetemcomitans was associated with periodontitis in diabetic
      patients (P < 0.05). CONCLUSIONS: The findings of the present study indicate that
      there might be differences in the subgingival microbiota between diabetic and non
      diabetic patients. In addition, P. gingivalis and A. actinomycetemcomitans were
      associated with periodontitis in patients without diabetes and patients with
      diabetes, respectively.

PMID- 23857868
TI  - A novel ex vivo culture model for inflammatory bone destruction.
AB  - Pathological alterations in the balance of bone metabolism are central to the
      progression of inflammatory bone diseases such as periodontal disease. We have
      developed and characterized a novel ex vivo murine mandible model of inflammatory
      bone destruction. Slices of mandible were cultured for 14 days in the presence or
      absence of P. gingivalis lipopolysaccharide (LPS) or pro-inflammatory cytokines.
      Following culture, cell viability and tissue histomorphometry were assessed with
      quantification of matrix proteins, resident osteoclasts, ligament cells,
      monocytes, macrophages, and neutrophils. In the absence of inflammatory factors,
      culture viability, osteoclasts, and matrix components were maintained. LPS or
      TNFalpha stimulation demonstrated an increase in cellular proliferation, monocyte
      cells, osteoclast differentiation, and matrix degradation. Pathophysiological
      bone metabolism can be induced via exposure to LPS and direct influence of
      TNFalpha within the model despite the absence of systemic circulation, providing
      a model for inflammatory bone destruction and investigation of the effects of
      novel therapeutics. 

PMID- 23857869
TI  - Real-world, open-label study to evaluate the effectiveness of mirtazapine on
      sleep quality in outpatients with major depressive disorder.
AB  - INTRODUCTION: The objective of this study was to evaluate the effect of
      mirtazapine on sleep quality in real-world outpatients with major depressive
      disorder (MDD). METHODS: Demographic characteristics of MDD outpatients were
      collected and the Pittsburgh Sleep Quality Index (PSQI) was assessed before and
      after treatment. RESULTS: In 3,924 MDD outpatients after treatment, sleep
      efficiency was significantly higher (P < 0.001), global PSQI score was
      significantly lower (P < 0.01), the reduction rates of sleep latency (P < 0.01)
      and global PSQI score (P < 0.001) were notably higher, and the proportion of
      using sleep medications (P < 0.05) was significantly lower in the mirtazapine
      group. In 3,455 MDD outpatients with insomnia after treatment, the reduction of
      sleep latency (P < 0.001), the prolongation of sleep duration (P < 0.001), and
      the increase in habitual sleep efficiency (P < 0.001) were more obvious, the
      reduction rates of sleep latency (P < 0.05) and global PSQI score (P < 0.001)
      were significantly higher, and the proportion of using sleep medications (P <
      0.001) was significantly lower in the mirtazapine group. In 469 MDD outpatients
      without insomnia after treatment, the reduction of sleep latency (P < 0.05), the
      increase in sleep duration (P < 0.001) and habitual sleep efficiency (P < 0.001),
      and the reduction rate of global PSQI score (P < 0.05) were significantly greater
      in the mirtazapine group. DISCUSSION: This real-world study suggests that
      mirtazapine improves sleep quality of MDD outpatients, and decreases the
      concomitant use of sleep medications.

PMID- 23857871
TI  - Urinary incontinence in Alzheimer's disease is associated with Clinical Dementia
      Rating-Sum of Boxes and Barthel Activities of Daily Living.
AB  - INTRODUCTION: Urinary incontinence (UI) and Alzheimer's disease (AD) are common
      in the elderly population and have increased rapidly in recent decades. This
      study aimed to evaluate the prevalence of UI and determine the neuropsychological
      characteristics of patients with AD and UI. METHODS: A total of 464 patients with
      probable AD were recruited, and the prevalence and type of UI were evaluated.
      Neuropsychological evaluation was assessed using the Mini-Mental Status
      Examination, Clinical Dementia Rating, Clinical Dementia Rating-Sum of Boxes,
      Global Deterioration Scale, Barthel Activities of Daily Living and Instrumental
      Activities of Daily Living. RESULTS: The prevalence of UI in patients with AD was
      24.8% (men 29.6%, women 23.0%). The two most common types of UI were urge
      incontinence (44.3%) and functional incontinence (25.3%). UI in patients with
      Alzheimer's disease was statistically significantly associated with Clinical
      Dementia Rating-Sum of Boxes (OR 1.56, 95% CI 1.21-2.01) and Barthel Activities
      of Daily Living (OR 1.34, 95%CI 1.22-1.47) after adjustment for different
      covariates. DISCUSSION: UI commonly occurred in patients with AD. The Clinical
      Dementia Rating-Sum of Boxes and Barthel Activities of Daily Living could be
      potential predictors for UI in patients with AD.

PMID- 23857870
TI  - Paediatric and adolescent alveolar soft part sarcoma: A joint series from
      European cooperative groups.
AB  - BACKGROUND: Alveolar soft part sarcomas (ASPS) are generally chemo- and radio
      resistant mesenchymal tumours, with no standardized treatment guidelines. We
      describe the clinical behaviour of paediatric ASPS and compare these features to
      previously reported adult series. PATIENTS AND METHODS: The clinical data of 51
      children and adolescents with ASPS, prospectively enrolled in or treated
      according to seven European Paediatric trials were analysed. RESULTS: Median age
      was 13 years [range: 2-21]. Primary sites included mostly limbs (63%). IRS post
      surgical staging was: IRS-I (complete resection) 35%, II (microscopic residual
      disease) 20%, III (gross residual disease) 18% and IV (metastases) 27%. Only 3 of
      the 18 evaluable patients (17%) obtained a response to conventional chemotherapy.
      After a median follow-up of 126 months (range: 9-240), 14/18 patients with IRS-I
      tumour, 10/10 IRS-II, 7/9 IRS-III and 2/14 IRS-IV were alive in remission.
      Sunitinib treatment achieved two very good partial responses in four patients.
      Ten-year overall survival (OS) and event free survival (EFS) was 78.0 +/- 7% and
      62.8 +/- 7% respectively. Stage IV, size >5 cm and T2 tumours had a poorer
      outcome, but only IRS staging was an independent prognostic factor. CONCLUSIONS:
      ASPS is a very rare tumour frequently arising in adolescents and in the
      extremities, and chemo resistant. Local surgical control is critical. ASPS is a
      poorly chemo sensitive tumour. For IRS-III/IV tumours, delayed radical local
      therapies including surgery are essential. Metastatic patients had a poor
      prognosis but targeted therapies showed promising results.

PMID- 23857872
TI  - Bridging current issues in science and society.
AB  - The challenges encountered in biotechnology research cannot be characterized
      solely by the scientific undertaking alone. Increasingly, scientists and policy
      makers are actively seeking ways to address social responsibility in
      biotechnological innovation. The European Commission has taken a highly visible
      position on the importance of societal opinion in innovation programs.
      Initiatives are underway worldwide aiming to address the fundamental fact that
      science and technology do not exist separately from the rest of society.

PMID- 23857873
TI  - Peripheral inflammatory markers in amnestic mild cognitive impairment.
AB  - OBJECTIVE: To prospectively monitor plasma inflammatory marker concentrations in
      peripheral blood, over 12 months, in subjects with amnestic mild cognitive
      impairment (MCI), and to determine the relationship between peripheral
      inflammatory markers and cognitive decline. METHODS: Seventy patients with
      amnestic MCI were recruited from two sites providing specialist memory assessment
      services in Manchester. The baseline assessment included physical examination,
      neuro-psychological testing and venous blood samples for C-reactive protein (CRP)
      and interleukin 6 (IL-6) concentrations. Sixty two participants were followed up
      after 12 months and the assessments were repeated. RESULTS: Data analysis
      revealed a significant rise in CRP, but not IL-6 concentrations over 12 months,
      which was not confounded by demographic variables. The neuro-psychological test
      scores had no association with CRP or IL-6 concentrations at baseline or 12
      months follow-up. CONCLUSION: This study adopted the unique approach of
      prospectively investigating peripheral inflammatory markers in a cohort with
      amnestic MCI. A significant rise in CRP concentrations over 12 months, but lack
      of significant association with cognition, provide no evidence for a relationship
      between systemic inflammation and cognitive decline in amnestic MCI.

PMID- 23857874
TI  - Copper-catalyzed intramolecular electrophilic carbofunctionalization of allylic
      amides.

PMID- 23857875
TI  - Should children with non-Hodgkin lymphoma be treated with different protocols
      according to histopathologic subtype?
AB  - BACKGROUND: The New York protocol, primarily developed to treat children with
      high-risk acute lymphoblastic leukemia (ALL), is characterized by early intensive
      chemotherapy followed by less intensive pulse chemotherapy during maintenance.
      This study was performed to evaluate the efficacy of this protocol in children
      with non-Hodgkin lymphoma (NHL), irrespective of histopathologic subtype.
      PROCEDURE: From January 1996 to December 2011, 146 newly diagnosed children and
      adolescents with NHL were treated with the modified New York protocol. Treatment
      duration was determined according to the stage. RESULTS: The 5-year failure-free
      survival (FFS), event-free survival (EFS), and overall survival (OS) rates were
      86.7 +/- 2.9%, 79.1 +/- 3.5%, and 84.7 +/- 3.1%, respectively. The 5-year FFS for
      patients with mature B-cell lymphoma, T-cell and NK-cell lymphoma (T/NK-cell
      lymphoma), and lymphoblastic lymphoma were 95.4 +/- 2.6%, 76.1 +/- 7.0%, and 82.1
      +/- 6.6%, respectively. In multivariate analysis, T/NK-cell lymphoma and non
      complete response (non-CR) at the end of induction chemotherapy were associated
      with a significant increase in treatment failure rate (relative risk [RR], 4.5, P
      = 0.03, and RR, 5.0, P = 0.002). CONCLUSION: The protocol appears to be
      efficacious in the treatment of children and adolescents with NHL, irrespective
      of histopathologic subtype. Achievement of CR after intensive induction
      chemotherapy was an important prognostic factor. Early response to treatment may
      be used to stratify risk groups and modify therapy in children with NHL.

PMID- 23857876
TI  - Treating heroin addiction: bridging the past and future--a Malaysian experience.

PMID- 23857877
TI  - Korean medication algorithm for bipolar disorder: second revision.
AB  - INTRODUCTION: The Feasibility Study of the Korean Medication Algorithm Project
      for Bipolar Disorder 2002 (KMAP-BP 2002) revealed its clinical usefulness in
      2005. Since much more data had become available since 2002, it was revised in
      2006 as KMAP-BP 2006. For the same reason, revision of KMAP-BP 2006 is now
      necessary. METHODS: The questionnaire, amended on the basis of KMAP-BP 2006 and
      new data, was sent to 94 experts, 65 of whom replied. RESULTS: In an acute manic
      episode, a combination of a mood stabilizer (MS) with an atypical antipsychotic
      (AAP) is recommended as first-line strategy. Monotherapy with MS is first-line in
      a hypomanic episode. Triple combination of a MS, an AAP, and an antidepressant
      (AD), is the first-line strategy in non-psychotic severe depression. Also MS+AAP
      and MS+AD are recommended as first-line. In psychotic bipolar depression,
      MS+AAP+AD, MS+AAP and AAP+AD are first-line strategies. In bipolar depression,
      lithium, lamotrigine and valproic acid are selected as first-line MS and
      quetiapine, olanzapine and aripiprazole are preferred antipsychotics. In
      maintenance treatment, a combination of MS with AAP and monotherapy of MS are
      recommended as first-line. DISCUSSION: In treating bipolar disorder, even the
      first step of treatment, the expert consensus has changed from our studies in
      2002 and 2006.

PMID- 23857878
TI  - Validation of a population-based method to assess drug-induced alterations in the
      QT interval: a self-controlled crossover study.
AB  - PURPOSE: The purpose of this study was to ascertain, in the context of an
      integrated health care delivery system, the association between a comprehensive
      list of drugs known to have potential QT liability and QT prolongation or
      shortening. METHODS: By using a self-controlled crossover study with 59 467
      subjects, we ascertained intra-individual change in log-linear regression
      corrected QT (QTcreg ) during the period between 1995 and mid-2008 for 90 drugs
      while adjusting for age, gender, race/ethnicity, comorbid conditions, number of
      electrocardiograms (ECGs), and time between pre-ECG and post-ECG. The proportion
      of users of each drug-developing incident long QT was also estimated. RESULTS:
      Two drugs (nicardipine and levalbuterol) had no statistically significant intra
      individual QTcreg shortening effects, 10 drugs had no statistically significant
      prolonging effect, and 78 (87%) of the drugs had statistically significant intra
      individual mean QTcreg lengthening effects, ranging from 7.6 ms for aripiprazole
      to 25.2 ms for amiodarone. Three drugs were associated with mean QTcreg
      prolongation of 20 ms or greater: amiodarone (antiarrhythmic), terfenadine
      (antihistaminic), and quinidine (antiarrhythmic); whereas 11 drugs were
      associated with mean QTcreg prolongation of 15 ms or greater but less than 20 ms:
      trimipramine (tricyclic antidepressant), clomipramine (tricyclic antidepressant),
      disopyramide (antiarrhythmic), chlorpromazine (antipsychotic), sotalol (beta
      blocker), itraconazole (antifungal), phenylpropanolamine
      (decongestant/anorectic), fenfluramine (appetite suppressant), midodrine
      (antihypotensive), digoxin (cardiac glycoside/antiarrhythmic), and procainamide
      (antiarrhythmic). CONCLUSIONS: QT prolonging effects were common and varied in
      strength. Our results lend support to past Food and Drug Administration
      regulatory actions and support the role for ongoing surveillance of drug-induced
      QT prolongation.

PMID- 23857880
TI  - Relationship between xerostomia and salivary flow rates in HIV-infected
      individuals.
AB  - AIM: The aim of the present study was to determine the relationship between self
      reported xerostomia and salivary flow rates among HIV-infected individuals.
      METHODS: A cross-sectional study was performed on 173 individuals (81 HIV
      infected individuals, mean age: 32 years, and 92 non-HIV controls, mean age: 30
      years). Subjective complaints of dry mouth, based on a self-report of xerostomia
      questions, and dry mouth, based on a visual analogue scale (VAS), were recorded
      along with measurements of salivary flow rate of both unstimulated and wax
      stimulated whole saliva. The relationship between subjective responses to the
      xerostomia questions, the VAS of dry mouth, and objective measurements of
      salivary flow rates were analyzed. RESULTS: Responses to the questions--Do you
      carry water or a saliva substitute? and Have you had taste disturbance?--were
      significantly different between HIV-infected and non-HIV individuals (P < 0.05).
      Individuals' responses to questions concerning dry mouth were significantly
      correlated with a low unstimulated salivary flow rate. A significant correlation
      between the VAS of dry mouth and salivary flow rates was observed (P = 0.023).
      CONCLUSIONS: Responses to self-reported xerostomia questions reflects low
      unstimulated salivary flow rates. Thus, questions concerning dry mouth might be
      useful tools to identify HIV-infected individuals with hyposalivation, especially
      at a resting stage.

PMID- 23857881
TI  - Subporphyrins with an axial B-C bond.
AB  - Axial fabrications of subporphyrins have been conveniently accomplished by the
      reaction of B(methoxo)triphenylsubporphyrin with Grignard reagents such as aryl-,
      heteroaryl-, ferrocenyl-, beta-styryl-, phenylethynyl-, and ethylmagnesium
      bromides. The axial groups thus introduced are not conjugated with the
      subporphyrin core. This situation leads to effective fluorescence quenching of
      subporphyrins when the axial group is strongly electron donating such as 4
      dimethylaminophenyl and ferrocenyl groups. 

PMID- 23857879
TI  - Development of a virtual spectrometer for chiroptical spectroscopies: the case of
      nicotine.
AB  - The impressive advances of computational spectroscopy in most recent years are
      providing robust and user-friendly multifrequency virtual spectrometers, which
      can also be used by nonspecialists to complement experimental studies. At the
      heart of these developments there are latest-generation models based on Density
      Functional Theory for the proper treatment of stereo-electronic effects, coupled
      to the polarizable continuum model to deal with bulk solvent effects, and low
      order perturbative treatments of anharmonic effects. Continuing our efforts to
      increase the range of application of virtual spectrometers, we report here about
      chiroptical spectroscopies with special reference to optical rotation and
      vibrational circular dichroism. The capabilities and possible limitations of our
      latest tool will be analyzed for the specific case of (S)-nicotine in vacuo and
      in different solvents.

PMID- 23857882
TI  - Nicotine dependence syndrome scale and craving: comparing nicotine-dependent
      individuals with and without comorbid alcohol dependence.
AB  - INTRODUCTION: Although several studies have explored craving for certain drugs,
      there is limited data describing the relationship between alcohol and nicotine
      craving from a multidimensional perspective among individuals with comorbid
      nicotine dependence (ND) and alcohol dependence (AD). METHODS: We compared a
      group of male patients diagnosed with ND and AD (n = 160) to a group of male
      patients diagnosed with ND only (n = 235). Smoking- and drinking-related clinical
      features were measured, including craving levels and the Nicotine Dependence
      Syndrome Scale (NDSS), which is a multidimensional questionnaire measuring ND.
      Subsequently, we studied factors that influenced smoking and alcohol craving in
      the ND and AD group. RESULTS: Regarding the NDSS, the sum, priority and tolerance
      scores were significantly higher in the ND and AD group compared with the ND only
      group (P < 0.000, P < 0.000 and P = 0.001, respectively). In the comorbid group,
      regression analyses revealed that alcohol craving and Fagerstrom Test for
      Nicotine Dependence (FTND) scores contributed to nicotine craving (beta
      coefficient = 0.37, P = 0.005 and beta coefficient = 0.35, P = 0.026,
      respectively) and these two factors explained 36% of the variance). Nicotine
      craving appeared to be the only factor that contributed to alcohol craving (beta
      coefficient = 0.35, P = 0.002), and nicotine craving explained 16% of the
      variance. DISCUSSION: This study may help clarify the clinical relationship
      between comorbid alcohol and nicotine dependence and help guide the development
      of effective treatment strategies for ND and AD patients.

PMID- 23857883
TI  - Use of a bioactive scaffold to stimulate anterior cruciate ligament healing also
      minimizes posttraumatic osteoarthritis after surgery.
AB  - BACKGROUND: Although anterior cruciate ligament (ACL) reconstruction is the
      treatment gold standard for ACL injury, it does not reduce the risk of
      posttraumatic osteoarthritis. Therefore, new treatments that minimize this
      postoperative complication are of interest. Bioenhanced ACL repair, in which a
      bioactive scaffold is used to stimulate healing of an ACL transection, has shown
      considerable promise in short-term studies. The long-term results of this
      technique and the effects of the bioenhancement on the articular cartilage have
      not been previously evaluated in a large animal model. HYPOTHESES: (1) The
      structural (tensile) properties of the porcine ACL at 6 and 12 months after
      injury are similar when treated with bioenhanced ACL repair, bioenhanced ACL
      reconstruction, or conventional ACL reconstruction, and all treatments yield
      results superior to untreated ACL transection. (2) After 1 year, macroscopic
      cartilage damage following bioenhanced ACL repair is similar to that in
      bioenhanced ACL reconstruction and less than in conventional ACL reconstruction
      and untreated ACL transection. STUDY DESIGN: Controlled laboratory study.
      METHODS: A total of 64 Yucatan mini-pigs underwent ACL transection and
      randomization to 4 experimental groups: no treatment, conventional ACL
      reconstruction, bioenhanced ACL reconstruction using a bioactive scaffold, and
      bioenhanced ACL repair using a bioactive scaffold. The biomechanical properties
      of the ligament or graft were examined and macroscopic assessments of the
      cartilage surfaces were performed after 6 and 12 months of healing. RESULTS: The
      structural properties (ie, linear stiffness, yield, and maximum loads) of the
      ligament after bioenhanced ACL repair were not significantly different from those
      in bioenhanced ACL reconstruction or conventional ACL reconstruction but were
      significantly greater than those in untreated ACL transection after 12 months of
      healing. Macroscopic cartilage damage after bioenhanced ACL repair was
      significantly less than that in untreated ACL transection and bioenhanced ACL
      reconstruction, and there was a strong trend (P = .068) for less macroscopic
      cartilage damage than in conventional ACL reconstruction in the porcine model at
      12 months. CONCLUSION: Bioenhanced ACL repair produces a ligament that is
      biomechanically similar to an ACL graft and provides chondroprotection to the
      joint after ACL surgery. CLINICAL RELEVANCE: Bioenhanced ACL repair may provide a
      new, less invasive treatment option that reduces cartilage damage following joint
      injury.

PMID- 23857884
TI  - CT and MRI measurements of tibial tubercle-trochlear groove distances are not
      equivalent in patients with patellar instability.
AB  - BACKGROUND: Tibial tubercle-trochlear groove distance (TT-TG) is a commonly used
      measurement for surgical decision making in patients with patellofemoral
      malalignment and instability. This measurement has historically been performed
      utilizing axial computed tomography (CT). More recently, magnetic resonance
      imaging (MRI) has been proposed as an equivalent method, but this has not yet
      been fully validated. PURPOSE: To determine the reliability of TT-TG distance
      measurements on both MRI and CT and to determine whether the measurements are
      interchangeable with one another. STUDY DESIGN: Cohort study (diagnosis); Level
      of evidence, 2. METHODS: All patients with patellar instability who underwent
      both CT and MRI of the knee from 2003 to 2011 were included (n = 59 knees in 54
      patients). Two fellowship-trained musculoskeletal radiologists measured the TT-TG
      distances for each patient by CT and MRI in a randomized, blinded fashion.
      Interobserver reliability was calculated between radiologists for both imaging
      modalities, and intermethod reliability was calculated between the 2 imaging
      modalities. The results are reported using intraclass correlation coefficients
      (ICCs) and Bland-Altman analysis. RESULTS: The 59 knees had a mean TT-TG distance
      of 16.9 mm (range, 8.3-25.8 mm) by CT and 14.7 mm (range, 1.5-25.1 mm) by MRI.
      Interobserver reliability between the radiologists was considered excellent for
      both CT and MRI (ICC = 0.777 and 0.843, respectively). When comparing CT to MRI,
      the ICC was considered only fair for each of the raters (0.532 and 0.539). Eleven
      patients (19%) had a TT-TG distance of >=20 mm on CT preoperatively and underwent
      distal realignment by tibial tubercle osteotomy. In this surgical subgroup, the
      mean TT-TG distance was 22.5 mm (range, 19.8-25.8 mm) by CT and only 18.7 mm
      (range, 14.4-22.8 mm) by MRI for a mean difference of 3.80 mm (P < .001).
      CONCLUSION: The TT-TG distance can be measured with excellent interrater
      reliability on both MRI and CT; however, the values derived from these 2 tests
      may not be interchangeable. This observation should be taken into consideration
      when MRI is used for surgical planning because MRI may underestimate the TT-TG
      distance when compared with CT.

PMID- 23857885
TI  - Does patient sex influence cartilage surgery outcome? Analysis of results at 5
      year follow-up in a large cohort of patients treated with Matrix-assisted
      autologous chondrocyte transplantation.
AB  - BACKGROUND: Sexual dimorphism in humans has already been documented at different
      levels, and preliminary findings also suggest the importance of patient sex on
      clinical outcome in the treatment of cartilage lesions. PURPOSE: To document and
      analyze the influence of sex on clinical outcome in a large cohort of patients
      treated with a cartilage regenerative procedure for knee chondral lesions and
      prospectively followed at midterm follow-up. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: A total of 250 knees were treated with matrix-assisted
      autologous chondrocyte transplantation (MACT) and prospectively evaluated with
      International Knee Documentation Committee (IKDC), EuroQol visual analog scale
      (EQ-VAS), and Tegner scores at 1-, 2-, and minimum 5-year follow-ups to compare
      results obtained in men and women. The lesions were focal International Cartilage
      Repair Society grade III-IV chondral knee defects involving femoral condyles,
      trochleae, and patellae. Two homogeneous groups of 56 male patients and 56 female
      patients were then selected by a blinded statistician for a matched-pair
      analysis. RESULTS: A statistically significant improvement in all the scores in
      both men and women was observed in the general population. The IKDC subjective
      score showed better results for men at all follow-up times: at 5 years, the mean
      IKDC subjective score was 79.5 +/- 18.6 versus 64.3 +/- 20.2 for men and women,
      respectively (P < .0005), and the same trend was confirmed with the EQ-VAS and
      Tegner scores. The matched-pair analysis confirmed the difference of final
      results achieved (74.1 +/- 19.8 vs 63.7 +/- 20.2, respectively; P = .006).
      However, men and women started with different preoperative levels, and the
      analysis of the improvement obtained was not significantly different. Finally,
      when scores were standardized for each patient, according to the mean score
      typical for the corresponding age and sex category in a healthy population, a sex
      related difference was not confirmed at any of the follow-ups. Etiological
      factors, lesion site, and preinjury activity level differed in women and men of
      the general population and were the confounding factors responsible for the
      different outcome not confirmed by the analysis of homogeneous cohorts of
      patients. CONCLUSION: Women have a different knee chondral lesion pattern and
      more often have unfavorable conditions related to the cause of injury, site, and
      activity level, and they also have lower raw, not standardized, scores. However,
      a matched-pair analysis with data standardized for the specific patient
      categories showed that, on equal terms, women have the same possibilities for
      successful outcome as men after surgical treatment for knee cartilage
      regeneration.

PMID- 23857886
TI  - Risk factors for recurrent anterior cruciate ligament reconstruction: a
      population study in Ontario, Canada, with 5-year follow-up.
AB  - BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) is routinely
      performed for symptomatic instability. Although it is a common procedure, there
      remain differences in surgical technique. Hospital administrative records in a
      public health care system were used to investigate the effect of patient,
      provider, and surgical factors on the risk of revision ACLR. PURPOSE: To define
      the rate and risk factors for ACL reoperation in Ontario, Canada, including both
      ipsilateral revision and contralateral primary procedures. STUDY DESIGN: Cohort
      study; Level of evidence, 3. METHODS: All primary elective ACLR procedures
      performed in Ontario (July 2003 to March 2008) in patients aged 15 to 60 years
      were identified via physician billing and hospital databases. Revision and
      contralateral ACLR were sought until January 2012. Patient factors (age, sex,
      comorbidity, income quintile, length of index hospital admission), provider
      factors (surgeon volume, academic hospital status), and surgical factors
      (allograft vs autograft; fixation type [screw, button, staple]; concomitant
      operative procedures) were used as covariates in a Cox proportional hazards
      survivorship model to generate hazard ratios (HRs) with confidence intervals
      (CIs) (alpha = .05). Kaplan-Meier survivorship curves with ACL revision as the
      end point were generated. RESULTS: A total of 12,967 ACLR procedures with a mean
      follow-up of 5.2 years were eligible for study using preset criteria. The
      revision rate was 2.6% (mean +/- SD, 2.91 +/- 1.71 years to revision). The rate
      of primary contralateral ACLR was 4.6% (mean, 2.95 +/- 1.81 years). In the Cox
      model, younger age (15-19 years) (HR, 2.1; 95% CI, 1.5-2.9; P < .001), ACLR
      performed at an academic hospital (HR, 1.6; 95% CI, 1.2-2.1; P < .001), and the
      use of allograft (HR, 1.7; 95% CI, 1.1-2.6; P = .02) significantly increased the
      risk of revision ACLR. Only younger age (HR, 2.1; 95% CI, 1.6-2.7; P < .001) was
      associated with an increased risk of contralateral ACLR. CONCLUSION:
      Contralateral ACLR was more frequent than revision ACLR in this population, while
      both surgical procedures were most common in patients younger than 20 years.
      Academic hospital status, but not surgeon volume, as well as the use of allograft
      also increased the risk for revision ACLR.

PMID- 23857887
TI  - Topographic analysis of the glenoid and proximal medial tibial articular
      surfaces: a search for the ideal match for glenoid resurfacing.
AB  - BACKGROUND: Current knowledge is lacking concerning the appropriate site of
      osteochondral allograft harvest to match glenoid shape for the purposes of
      glenoid resurfacing. This has led to difficulty with adequate restoration of the
      geometry of the glenoid with currently available techniques. HYPOTHESIS: The
      medial tibial plateau will provide a suitable osteochondral harvest site because
      of its concavity and anatomic similarity to the glenoid. STUDY DESIGN:
      Descriptive laboratory study. METHODS: Computed tomography (CT) was performed on
      4 cadaveric proximal tibias and 4 scapulae, allowing for 16 glenoid-tibial
      comparative combinations. Three-dimensional CT models were created and exported
      into point-cloud models. A local coordinate map of the glenoid and medial tibial
      plateau articular surfaces was created. Two zones of the medial tibial articular
      surface (anterior and posterior) were quantified. The glenoid articular surface
      was defined as a best-fit circle of the glenoid articular surface maintaining a 2
      mm bony rim. This surface was virtually placed on a point on the tibial articular
      surface in 3D space. The tibial surface was segmented, and its 3D surface
      orientation was determined with respect to its surface. The 3D orientation of the
      glenoid surface was reoriented so that the direction of the glenoid surface
      matched that of the tibial surface. The least distances between the point-clouds
      on the glenoid and tibial surfaces were calculated. The glenoid surface was
      rotated 360 degrees  in 1 degrees  increments, and the mean least distance was
      determined at each rotating angle. RESULTS: When the centroid of the glenoid
      surface was placed on the medial tibial articular surface, it covered
      approximately two-thirds of the anterior or posterior tibial surfaces. Overall,
      the mean least distance difference in articular congruity of all 16 glenoid
      medial tibial surface combinations was 0.74 mm (standard deviation, +/-0.13 mm).
      The mean least distance difference of the anterior and posterior two-thirds of
      the medial tibial articular surface was 0.72 mm (+/-0.13 mm) and 0.76 mm (+/-0.16
      mm), respectively. There was no significant difference between the anterior and
      posterior two-thirds of the tibia with regard to topographic match of the glenoid
      (P = .187). CONCLUSION: The findings suggest that the medial tibial articular
      surface provides an appropriate anatomic match to the glenoid articular surface.
      Both the anterior and posterior two-thirds of the medial tibial articular surface
      are potential sites for osteochondral graft harvest. CLINICAL RELEVANCE: This
      method can be applied to future studies evaluating the ideal sites of graft
      harvest to treat zonal glenoid bone wear and/or loss.

PMID- 23857889
TI  - Electron tomography: three-dimensional imaging of real crystal structures at
      atomic resolution.

PMID- 23857888
TI  - When one loses empathy: its effect on carers of patients with dementia.
AB  - The effects of empathy loss in frontotemporal dementia (FTD) and Alzheimer
      disease (AD) on carer symptomatology were investigated. Carers of patients with 2
      clinical subtypes of FTD (behavioral-variant FTD [bvFTD] = 18; semantic dementia
      [SD] = 14) and AD (n = 18) completed the Interpersonal Reactivity Index (IRI), a
      standardized questionnaire of empathy as well as a measure of perceived burden
      (Zarit Burden Interview) and the quality of the marital relationship (Intimate
      Bond Measure). Patient ratings were also obtained on the IRI. Loss of empathy was
      most striking in the bvFTD group with a marked discrepancy observed between carer
      and patient ratings for change in emotional warmth and the ability to take the
      perspective of others. Empathy loss in bvFTD was associated with a loss of a
      caring marital relationship. Empathic deficits in SD were milder by comparison to
      bvFTD and correlated with disease severity and increased perceived carer burden.
      The behavioral pattern observed in AD differed from the FTD syndromes; deficits
      were observed only for measures of personal distress with carers reporting that
      patients were less able to handle emotionally evocative situations. Results
      highlight that changes in aspects of empathy differ across dementia syndromes and
      are associated with differing carer and clinical variables. These findings might
      be explained by the progression of atrophy in regions that are known to be
      critical for empathy and social behavior and has implications for the delivery
      and planning of services in dementia. 

PMID- 23857890
TI  - Genome-wide association analysis accounting for environmental factors through
      propensity-score matching: application to stressful live events in major
      depressive disorder.
AB  - Stressful life events are an established trigger for depression and may
      contribute to the heterogeneity within genome-wide association analyses. With
      depression cases showing an excess of exposure to stressful events compared to
      controls, there is difficulty in distinguishing between "true" cases and a
      "normal" response to a stressful environment. This potential contamination of
      cases, and that from genetically at risk controls that have not yet experienced
      environmental triggers for onset, may reduce the power of studies to detect
      causal variants. In the RADIANT sample of 3,690 European individuals, we used
      propensity score matching to pair cases and controls on exposure to stressful
      life events. In 805 case-control pairs matched on stressful life event, we tested
      the influence of 457,670 common genetic variants on the propensity to depression
      under comparable level of adversity with a sign test. While this analysis
      produced no significant findings after genome-wide correction for multiple
      testing, we outline a novel methodology and perspective for providing
      environmental context in genetic studies. We recommend contextualizing depression
      by incorporating environmental exposure into genome-wide analyses as a
      complementary approach to testing gene-environment interactions. Possible
      explanations for negative findings include a lack of statistical power due to
      small sample size and conditional effects, resulting from the low rate of
      adequate matching. Our findings underscore the importance of collecting
      information on environmental risk factors in studies of depression and other
      complex phenotypes, so that sufficient sample sizes are available to investigate
      their effect in genome-wide association analysis.

PMID- 23857892
TI  - Aldehyde oxidase 1 (AOX1) in human liver cytosols: quantitative characterization
      of AOX1 expression level and activity relationship.
AB  - Aldehyde oxidase 1 (AOX1) is a cytosolic enzyme highly expressed in liver and
      plays a key role in metabolizing drugs containing aromatic azaheterocyclic
      substituents. Rapid metabolism catalyzed by AOX1 can cause a drug to exhibit high
      clearance, low exposure, and hence decreased efficacy or even increased toxicity
      (if AOX1 generated metabolites are toxic). There is a need to develop the
      correlation between AOX1 expression levels and AOX1-substrate clearance. A fast,
      sensitive, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method was developed to quantify AOX1 in human liver cytosol for the first time.
      This LC-MS/MS method includes a straightforward ultrafiltration fractionation
      step and gives great selectivity and wide dynamic range (5.2 pM to 20.7 nM). The
      AOX1 levels in human liver cytosols of 20 donors were quantified using this
      method to investigate individual differences in AOX1 expression. No significant
      individual or gender differences in AOX1 levels were observed, although male
      donors exhibited a broader distribution than female donors (0.74-2.30 pmol/mg
      versus 0.74-1.69 pmol/mg, respectively). The AOX1 protein levels measured by LC
      MS/MS were consistent with those measured by an enzyme-linked immunosorbent
      assay. Several donors have a normal AOX1 protein level but low enzyme activity,
      which might be due to cofactor deficiency, single nucleotide polymorphism, or
      homodimer dissociation. Cytosols from donors with chronic alcohol consumption had
      low AOX1-catalyzed carbazeran oxidation activities (<51 ul/min per milligram
      compared with a median of 455 ul/min per milligram), but preserved similar AOX1
      protein expression levels (approximately 15% less than the median value). 

PMID- 23857891
TI  - In vitro-in vivo correlation for low-clearance compounds using hepatocyte relay
      method.
AB  - In vitro-in vivo correlation (IVIVC) of intrinsic clearance in preclinical
      species of rat and dog was established using the hepatocyte relay method to
      support high-confidence prediction of human pharmacokinetics for low-clearance
      compounds. Good IVIVC of intrinsic clearance was observed for most of the
      compounds, with predicted values within 2-fold of the observed values. The
      exceptions involved transporter-mediated uptake clearance or metabolizing enzymes
      with extensive extrahepatic contribution. This is the first assay available to
      address low clearance challenges in preclinical species for IVIVC in drug
      discovery. It extends the utility of the hepatocyte relay method in addressing
      low clearance issues. 

PMID- 23857893
TI  - Barriers to seeking help among children with attention deficit hyperactivity
      disorder in Taiwan.
AB  - BACKGROUND: This study explores barriers to seeking help for children with
      attention deficit hyperactivity disorder (ADHD) in Taiwan. METHODS: The
      caregivers (mainly mothers) of 104 children with ADHD were evaluated on an
      outpatient basis. The mean age of the ADHD children was 9.47 +/- 1.97 years.
      Sociodemographic data and barriers related to seeking help were collected,
      including age, sex, multiple medical care seeking and parents' attitude toward
      the use of stimulants. The intensity of the barriers to seeking help was compared
      between good and/or poor compliance groups. RESULTS: Those who took
      methylphenidate (MPH) regularly are less likely engage in multiple medical care
      seeking (P < 0.05) and are more likely to choose to seek help from a child
      psychiatrist as a first response to symptoms (P < 0.05). Boys with ADHD favored
      medical MPH treatment when seeking help. ADHD children of mothers with a higher
      education were more likely to refuse psychiatric treatment in the initial stage
      and seek alternative treatment such as sensory integration training. DISCUSSION:
      There is a need to clarify how the misdiagnosis of ADHD as sensory integration
      dysfunction may impede seeking effective mental health care. Policy makers should
      enhance the understanding of parents with children with ADHD to increase
      treatment effectiveness and adherence.

PMID- 23857894
TI  - Service training of Teachers of Psychiatry Meeting in Shanghai, China.

PMID- 23857895
TI  - Expanding the metabolic engineering toolbox with directed evolution.
AB  - Cellular systems can be engineered into factories that produce high-value
      chemicals from renewable feedstock. Such an approach requires an expanded toolbox
      for metabolic engineering. Recently, protein engineering and directed evolution
      strategies have started to play a growing and critical role within metabolic
      engineering. This review focuses on the various ways in which directed evolution
      can be applied in conjunction with metabolic engineering to improve product
      yields. Specifically, we discuss the application of directed evolution on both
      catalytic and non-catalytic traits of enzymes, on regulatory elements, and on
      whole genomes in a metabolic engineering context. We demonstrate how the goals of
      metabolic pathway engineering can be achieved in part through evolving cellular
      parts as opposed to traditional approaches that rely on gene overexpression and
      deletion. Finally, we discuss the current limitations in screening technology
      that hinder the full implementation of a metabolic pathway-directed evolution
      approach. 

PMID- 23857896
TI  - Construction of quaternary stereocenters: asymmetric alpha-amination of branched
      aldehydes catalyzed by monoimide substituted cyclohexane-1,2-diamines.
AB  - A highly efficient enantioselective alpha-amination of branched aldehydes
      catalyzed by chiral imide monosubstituted 1,2-diamine derivatives was reported to
      afford the quaternary stereogenic centers in excellent yields (up to 99%) and
      enantioselectivities (up to 97% ee). Chirality 25:668-672, 2013. (c) 2013 Wiley
      Periodicals, Inc. 

PMID- 23857897
TI  - Validation of the Chinese version of Perception of Care in an acute psychiatric
      ward in Hong Kong.
AB  - INTRODUCTION: This study aimed to validate and culturally adapt the Perception of
      Care (PoC) for patients receiving acute psychiatric inpatient services in Hong
      Kong. METHODS: The PoC was translated and culturally adapted into a written
      Chinese version (C-PoC). Subjects completed C-PoC, Chinese version of Admission
      Experience Survey (C-AES) and World Health Organization Quality of Life Measure
      (WHOQOL-BREF). They were then rated by assessors with Brief Psychiatric Rating
      Scale (BPRS), Hamilton Rating Scale for Depression, Hamilton Rating Scale for
      Anxiety and Extrapyramidal Symptom Rating Scale. Explorative factor analysis and
      correlation between C-PoC, WHOQOL-BREF and C-AES served as the theoretical basis
      of construct validity. Multivariate analysis was used to identify predictors of
      satisfaction. RESULTS: The C-PoC has a four-factor structure that resembles the
      original scale with demonstrating satisfactory construct validity and test-re
      test reliability. Psychiatric symptom ratings did not predict any satisfaction
      ratings. Extrapyramidal symptoms predicted poorer satisfaction. Younger patients
      with affective diagnoses had better satisfaction. DISCUSSION: The C-PoC is a
      psychometrically sound translation of the original scale. The current study paves
      the way for further studies among Chinese-speaking communities on the
      determinants and implications of patients' satisfaction by offering a
      psychometrically sound and yet concise instrument.

PMID- 23857900
TI  - Mussel-mimetic, bioadhesive polymers from plant-derived materials.
AB  - AIM: Mussel-mimetic, bioadhesive polymers are synthesized from plant-derived
      sources. The strong adhesive action is caused by interactions between the
      catechol groups at the end of the polymer terminal chains and the substrate
      surface. Here, we present a preliminary study of the adhesion properties and a
      discussion of the adhesion mechanism. METHODS: Two bioadhesive polymers were
      synthesized from natural plant-derived monomers by the transesterification of:
      (a) caffeic acid (3,4-dihydroxycinnamic acid; DHCA) and p-coumaric acid (4
      hydroxycinnamic acid; 4HCA) to produce poly(DHCA-co-4HCA); and (b) 4
      dihydroxyhydrocinnamic acid (DHHCA) and 3-(3-hydroxyphenyl) propionic acid
      (3HPPA) to produce poly(DHHCA-co-3HPPA). Thermoplastic poly(DHCA-co-4HCA) or
      poly(DHHCA-co-3HPPA) was placed between glass, carbon, steel, or bovine dentin
      substrates, and a lap shear adhesion test was conducted to compare them using
      conventional cyanoacrylate glue and epoxy resin. RESULTS: The greatest adhesion
      for all tested substrates was exhibited by poly(DHHCA-co-3HPPA), followed by
      epoxy resin adhesive, poly(DHCA-co-4HCA), and cyanoacrylate adhesive. The
      adhesive strength of poly(DHHCA-co-3HPPA) was greater than 25.6 MPa for glass,
      29.6 MPa for carbon, 15.7 MPa for steel, and 16.3 MPA for bovine dentin.
      CONCLUSION: The adhesion of poly(DHHCA-co-3HPPA) might be the strongest reported
      for a mussel-mimic adhesive system, and could be a feasible alternative to
      petroleum adhesives.

PMID- 23857901
TI  - Asymmetric catalytic 1,6-conjugate addition/aromatization of para-quinone
      methides: enantioselective introduction of functionalized diarylmethine
      stereogenic centers.

PMID- 23857902
TI  - Tests for an upper percentile of a lognormal distribution based on samples with
      multiple detection limits and sample-size calculation.
AB  - The problem of determining sample size for testing an upper percentile of a
      lognormal distribution based on samples with multiple detection limits is
      considered. Two tests, the signed likelihood ratio test and another test based on
      a pivotal statistic, are outlined. These tests are very satisfactory in
      controlling type I error rates and comparable in terms of powers. Procedures and
      R codes for calculating sample sizes for these tests to attain a specified power
      are given. It is noted that for guaranteeing a given power, increased sample size
      is necessary due to the presence of detection limits, and the required sample
      size goes up as the proportion of non-detects goes up. It is also noted that in
      the multiple detection limit scenario, sample-size determination does not require
      knowledge of the proportions of non-detects that are expected to be below the
      individual detection limits; rather, what is required is a knowledge of the
      overall percentage of non-detects that is to be expected in the entire sample.
      Sample-size calculation is illustrated using a practical situation.

PMID- 23857903
TI  - Social relationship and health among students with low social desirability.
AB  - INTRODUCTION: This survey aimed to probe the associations between altruism,
      social support and subjective health among incoming students with low level of
      social desirability. METHODS: Totally, 5,634 incoming university students were
      assessed and 2,472 students with a low tendency toward social desirability were
      recruited for analysis. RESULTS: The results indicated that altruism and
      perceived social support were correlated and both could predict subjective health
      simultaneously. Path analysis indicated that altruism may promote health directly
      and indirectly by social support. DISCUSSION: Developing curriculums to enhance
      altruism and social support could be an important issue for university students.

PMID- 23857905
TI  - Size and CT density of iodine-containing ethosomal vesicles obtained by membrane
      extrusion: potential for use as CT contrast agents.
AB  - Computed tomography (CT) is the primary non-invasive imaging technique used for
      most patients with suspected liver disease. In order to improve liver-specific
      imaging properties and prevent toxic effects in patients with compromised renal
      function, we investigated the encapsulation of iodine within ethosomal vesicles.
      As a first step in the development of novel contrast agents using ethosomes for
      CT imaging applications, iodine was entrapped within ethosomes and iodine
      containing ethosomes of the desired size were obtained by extrusion using a
      polycarbonate membrane with a defined pore size. Ethosomes containing iodine
      showed a relatively high CT density, which decreased when they were extruded, due
      to the rupture and re-formation of the lipid bilayer of the ethosome. However,
      when a solution with a high iodine concentration was used as a dispersion media
      during the extrusion process, the decrease in CT density could be prevented. In
      addition, ethosomes containing iodine were taken up efficiently by macrophages,
      which are abundant in the liver, and these ethosomes exhibited no cellular
      toxicity. These results demonstrate that iodine could be entrapped within
      ethosomal vesicles, giving the ethosomes a relatively high CT density, and that
      the extrusion technique used in this study could conveniently and reproducibly
      produce ethosomal vesicles with a desired size. Therefore, ethosomes containing
      iodine, as prepared in this study, have potential as contrast agents with
      applications in CT imaging. 

PMID- 23857904
TI  - The genome sequence of Leishmania (Leishmania) amazonensis: functional annotation
      and extended analysis of gene models.
AB  - We present the sequencing and annotation of the Leishmania (Leishmania)
      amazonensis genome, an etiological agent of human cutaneous leishmaniasis in the
      Amazon region of Brazil. L. (L.) amazonensis shares features with Leishmania (L.)
      mexicana but also exhibits unique characteristics regarding geographical
      distribution and clinical manifestations of cutaneous lesions (e.g. borderline
      disseminated cutaneous leishmaniasis). Predicted genes were scored for
      orthologous gene families and conserved domains in comparison with other human
      pathogenic Leishmania spp. Carboxypeptidase, aminotransferase, and 3'
      nucleotidase genes and ATPase, thioredoxin, and chaperone-related domains were
      represented more abundantly in L. (L.) amazonensis and L. (L.) mexicana species.
      Phylogenetic analysis revealed that these two species share groups of amastin
      surface proteins unique to the genus that could be related to specific features
      of disease outcomes and host cell interactions. Additionally, we describe a
      hypothetical hybrid interactome of potentially secreted L. (L.) amazonensis
      proteins and host proteins under the assumption that parasite factors mimic their
      mammalian counterparts. The model predicts an interaction between an L. (L.)
      amazonensis heat-shock protein and mammalian Toll-like receptor 9, which is
      implicated in important immune responses such as cytokine and nitric oxide
      production. The analysis presented here represents valuable information for
      future studies of leishmaniasis pathogenicity and treatment. 

PMID- 23857906
TI  - Electroconvulsive therapy without consent from patients: one-year follow-up
      study.
AB  - INTRODUCTION: No previous study has been designed to analyze the reasons for
      electroconvulsive therapy (ECT) without patients' consent. In the present study
      we compared the clinical characteristics and one-year outcomes between patients
      with refusal to undergo ECT and patients without competency for ECT consent.
      METHODS: In a retrospective cohort study, 29 patients were treated with ECT
      without providing consent between 1 January 2006 and 31 August 2010. A surrogate
      family member gave informed consent for ECT to meet current legal requirements.
      Patients were assigned to one of two groups: a consent-refusal group comprising
      patients who refused to give consent for ECT and could clearly say "no" or argue
      with psychiatric staff about receiving ECT; and a consent-incompetent group
      comprising patients who were incompetent for consent but underwent ECT passively
      or reluctantly without argument. RESULTS: The patients were clinically diagnosed
      with schizoaffective disorder (n = 6), psychotic disorder (n = 12), bipolar I
      disorder (n = 8) and major depressive disorder with psychotic features (n = 3).
      The consent-incompetent patients had longer hospital stays and more recurrence in
      one year than the consent-refusal patients, which may be because the former group
      had more psychotic disorders and fewer mood disorders. All patients improved
      rapidly and efficiently. However, remission was temporal in two-thirds of
      patients and the rehospitalization rate in one year was 66% (n = 19). DISCUSSION:
      ECT can be applied early, emergently and successfully to patients who have a wide
      range of psychiatric disorders and life-threatening conditions without threat of
      lawsuits, even during their first hospitalization.

PMID- 23857909
TI  - An MEKC assay for the therapeutic drug monitoring of cefepime.
AB  - The development of a robust assay based on MEKC for cefepime in human serum and
      plasma with internal quality assurance is reported. Sample preparation comprises
      protein precipitation in the presence of SDS at pH 4.5. This is a gentle approach
      for which decomposition of cefepime during sample handling is negligible. After
      hydrodynamic sample injection of the supernatant, analysis occurs in a
      phosphate/borate buffer at pH 9.1 with 75 mM SDS using normal polarity and
      analyte detection at 257 nm. The MEKC run time interval and throughput are about
      5 min and seven samples per hour, respectively. The calibration range for
      cefepime is 1-60 MUg/mL, with 1 MUg/mL being the LOQ. The performance of the
      assay with multilevel internal calibration was assessed with calibration and
      control samples. The assay is shown to be simple, inexpensive, reproducible, and
      robust. It was applied to determine cefepime levels in the sera of critically ill
      patients and to assess the instability of cefepime in patient and control
      samples. Our data revealed that serum containing cefepime can be stored at -20
      degrees C for a short time, whereas for long-term storage, samples have to be
      kept at -70 degrees C.

PMID- 23857907
TI  - Ku70 and non-homologous end joining protect testicular cells from DNA damage.
AB  - Spermatogenesis is a complex process that generates haploid germ cells or spores
      and implements meiosis, a succession of two special cell divisions that are
      required for homologous chromosome segregation. During prophase to the first
      meiotic division, homologous recombination (HR) repairs Spo11-dependent DNA
      double-strand breaks (DSBs) in the presence of telomere movements to allow for
      chromosome pairing and segregation at the meiosis I division. In contrast to HR,
      non-homologous end joining (NHEJ), the major DSB repair mechanism during the G1
      cell cycle phase, is downregulated during early meiotic prophase. At somatic
      mammalian telomeres, the NHEJ factor Ku70/80 inhibits HR, as does the Rap1
      component of the shelterin complex. Here, we investigated the role of Ku70 and
      Rap1 in meiotic telomere redistribution and genome protection in spermatogenesis
      by studying single and double knockout mice. Ku70(-/-) mice display reduced
      testis size and compromised spermatogenesis, whereas meiotic telomere dynamics
      and chromosomal bouquet formation occurred normally in Ku70(-/-) and Ku70(-/
      )Rap1(Delta/Delta) knockout spermatocytes. Elevated mid-preleptotene frequencies
      were associated with significantly increased DNA damage in Ku-deficient B
      spermatogonia, and in differentiated Sertoli cells. Significantly elevated levels
      of gammaH2AX foci in Ku70(-/-) diplotene spermatocytes suggest compromised
      progression of DNA repair at a subset of DSBs. This might explain the elevated
      meiotic metaphase apoptosis that is present in Ku70-deficient stage XII testis
      tubules, indicating spindle assembly checkpoint activation. In summary, our data
      indicate that Ku70 is important for repairing DSBs in somatic cells and in late
      spermatocytes of the testis, thereby assuring the fidelity of spermatogenesis.

PMID- 23857908
TI  - Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12.
AB  - We report here the genetic basis for a form of progressive hereditary spastic
      paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing
      revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene
      recently implicated in neurodegeneration with brain iron accumulation (NBIA). The
      same mutation was subsequently also found in a Brazilian family with features of
      NBIA, and we identified another NBIA patient with a three-nucleotide deletion
      (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro
      mutations have a common origin, but MRI scans showed no brain iron deposition in
      the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA
      variants resulted in similar alterations in the subcellular distribution of
      C19orf12. The SPG43 and NBIA variants reported here as well as the most common
      C19orf12 missense mutation reported in NBIA patients are found within a highly
      conserved, extended hydrophobic domain in C19orf12, underscoring the functional
      importance of this domain. 

PMID- 23857910
TI  - Elevated serum copper and ceruloplasmin levels in Alzheimer's disease.
AB  - INTRODUCTION: Copper takes part in a variety of biological reduction-oxidation
      (redox) processes, and is an important cofactor of many redox enzymes.
      Ceruloplasmin, the copper-transporting protein, also possesses an important redox
      capacity. METHODS: We assessed serum copper, ceruloplasmin and free-copper levels
      in 89 patients with Alzheimer's disease (AD) (mean age, 77.83 years; 41 men, 48
      women) and in 118 healthy individuals (mean age, 69.93 years; 50 men, 68 women).
      High (>=75th percentile), medium, and low (<=25th percentile) copper,
      ceruloplasmin and free-copper groups were classified according to their serum
      level. RESULTS: Serum copper (P = 0.026) and ceruloplasmin (P = 0.001) levels
      were significantly higher in the AD group than in the control group. There was no
      significant difference in serum free-copper levels between AD and healthy elderly
      groups (P = 0.975). After adjusting for age differences, serum copper (P = 0.049)
      was still significantly higher in the AD group. Furthermore, serum copper levels
      correlated with scores on the Boston naming test (r = -0.151, P = 0.037),
      indicating a close relationship between copper levels and cognitive abilities.
      DISCUSSION: The significant association between the copper concentration in
      peripheral serum and AD with elevated copper levels found in patients with AD is
      likely linked to the evolution of AD. Serum copper levels were significantly
      negatively correlated with scores on cognitive test subscores. AD patients may
      have significantly more "defective" ceruloplasmin, that is, apo-ceruloplasmin
      lacking its copper, than in healthy controls.

PMID- 23857911
TI  - Effectiveness of Artocarpus lakoocha extract, poloxamer 407, on Enterococcus
      faecalis in vitro.
AB  - AIM: The antiviral activities of Artocarpus lakoocha (A. lakoocha) extract have
      been reported in a number of studies; however, data regarding its antibacterial
      capability are limited. The aim of the present study was to examine the
      effectiveness of A. lakoocha extract, poloxamer 407, on Enterococcus faecalis (E.
      faecalis). METHODS: The effect of the antimicrobial activity of A. lakoocha
      extract and A. lakoocha extract, poloxamer 407, against E. faecalis was
      investigated. The antibacterial efficacy of A. lakoocha extract, poloxamer 407,
      against E. faecalis was compared to calcium hydroxide in a tooth model. RESULTS:
      The minimal inhibitory concentration and minimal bactericidal concentration (MBC)
      of A. lakoocha extract against E. faecalis were 0.39 +/- 0 mg/mL and 3.12 +/- 0
      mg/mL, respectively; the MBC of calcium hydroxide against E. faecalis was 31.25
      +/- 0 mg/mL. In the tooth model, the E. faecalis count in all groups
      significantly decreased as the depth into the dentin increased compared to the
      control. There were no significant differences between 4% A. lakoocha extract
      poloxamer and UltraCal XS at any time period (P > 0.05) with one exception: at a
      depth of 0.6 mm on day 5, UltraCal XS had a significantly greater colonization
      than 4% A. lakoocha extract poloxamer. CONCLUSION: A. lakoocha extract, poloxamer
      407, might be a useful alternative for antimicrobial medication in endodontic
      treatment. However, controlled clinical studies to evaluate its efficacy are
      needed.

PMID- 23857912
TI  - Psychological and social consequences of losing a child in a natural or human
      made disaster: a review of the evidence.
AB  - Exposure to natural and human-made disasters is associated with long-term health
      consequences, including for mental health. Parents who have lost children,
      particularly their only children, in any circumstances are also at increased risk
      of developing mental health problems. The aim of this study was to review the
      available evidence about the psychological and social consequences for parents
      who had faced these circumstances simultaneously through losing children in a
      disaster. Systematic searching of the English and Chinese language literatures
      about the psychological and social functioning of bereaved parents after
      disasters revealed that a small number of studies met inclusion criteria. The
      results showed that bereaved parents had more mental health problems than
      bereaved spouses and non-bereaved parents, and mothers appeared to be more
      vulnerable to mental health problems than fathers. Potential protective factors
      for bereaved parents' mental health included having psychological interventions,
      having adequate social support, seeing their children's bodies and having a
      subsequent baby. Although the literature was modest and methodologically diverse,
      there was a consistent finding that parents who have lost children in disasters
      were at high risk of suffering mental health problems, especially bereaved
      mothers. As there was little evidence, further studies are needed to understand
      the best advice and interventions to offer bereaved parents and provide enhanced
      mental health care of such bereaved populations after disasters. 

PMID- 23857914
TI  - Iridium-catalyzed, diastereoselective dehydrogenative silylation of terminal
      alkenes with (TMSO)2MeSiH.

PMID- 23857913
TI  - Curcumin I mediates neuroprotective effect through attenuation of quinoprotein
      formation, p-p38 MAPK expression, and caspase-3 activation in 6-hydroxydopamine
      treated SH-SY5Y cells.
AB  - 6-Hydroxydopamine (6-OHDA) selectively enters dopaminergic neurons and undergoes
      auto-oxidation resulting in the generation of reactive oxygen species and
      dopamine quinones, subsequently leading to apoptosis. This mechanism mimics the
      pathogenesis of Parkinson's disease and has been used to induce experimental
      Parkinsonism in both in vitro and in vivo systems. In this study, we investigated
      the effects of curcumin I (diferuloylmethane) purified from Curcuma longa on
      quinoprotein production, phosphorylation of p38 MAPK (p-p38), and caspase-3
      activation in 6-OHDA-treated SH-SY5Y dopaminergic cells. Pretreatment of SH-SY5Y
      with curcumin I at concentrations of 1, 5, 10, and 20 MUM, significantly
      decreased the formation of quinoprotein and reduced the levels of p-p38 and
      cleaved caspase-3 in a dose-dependent manner. Moreover, the levels of the
      dopaminergic neuron marker, phospho-tyrosine hydroxylase (p-TH), were also dose
      dependently increased upon treatment with curcumin I. Our results clearly
      demonstrated that curcumin I protects neurons against oxidative damage, as shown
      by attenuation of p-p38 expression, caspase-3-activation, and toxic quinoprotein
      formation, together with the restoration of p-TH levels. This study provides
      evidence for the therapeutic potential of curcumin I in the chemoprevention of
      oxidative stress-related neurodegeneration.

PMID- 23857915
TI  - Plant-derived pharmaceuticals for the developing world.
AB  - Plant-produced vaccines and therapeutic agents offer enormous potential for
      providing relief to developing countries by reducing the incidence of infant
      mortality caused by infectious diseases. Vaccines derived from plants have been
      demonstrated to effectively elicit an immune response. Biopharmaceuticals
      produced in plants are inexpensive to produce, require fewer expensive
      purification steps, and can be stored at ambient temperatures for prolonged
      periods of time. As a result, plant-produced biopharmaceuticals have the
      potential to be more accessible to the rural poor. This review describes current
      progress with respect to plant-produced biopharmaceuticals, with a particular
      emphasis on those that target developing countries. Specific emphasis is given to
      recent research on the production of plant-produced vaccines toward human
      immunodeficiency virus, malaria, tuberculosis, hepatitis B virus, Ebola virus,
      human papillomavirus, rabies virus and common diarrheal diseases. Production
      platforms used to express vaccines in plants, including nuclear and chloroplast
      transformation, and the use of viral expression vectors, are described in this
      review. The review concludes by outlining the next steps for plant-produced
      vaccines to achieve their goal of providing safe, efficacious and inexpensive
      vaccines to the developing world. 

PMID- 23857916
TI  - Open-label, dose-titration tolerability study of atomoxetine hydrochloride in
      Korean, Chinese, and Taiwanese adults with attention-deficit/hyperactivity
      disorder.
AB  - INTRODUCTION: The primary objective of this study was to assess the overall
      safety and tolerability of atomoxetine in Korean, Chinese, and Taiwanese adults
      with attention-deficit/hyperactivity disorder (ADHD). METHODS: A total of 44
      patients aged >=18 years who met the Conners' Adult ADHD Diagnostic Interview for
      DSM-IV diagnostic criteria for ADHD were enrolled from China, Korea, and Taiwan.
      In this open-label, dose-escalation study, patients received atomoxetine orally
      once daily over a period of eight weeks, starting at 40 mg/day (one week) up to a
      maximum dosage of 120 mg/day. Tolerability was evaluated by rate of
      discontinuation due to adverse events. Safety was assessed by recording all
      adverse events, laboratory tests, vital signs, and electrocardiograms. ADHD
      symptoms were evaluated by the Conners' Adult ADHD Rating Scale-Investigator
      Rated: Screening Version (CAARS-Inv:SV) for efficacy assessment. RESULTS: Thirty
      four patients (77.3%) completed the study. Atomoxetine was well tolerated with a
      discontinuation rate of 2.3% (1/44) due to adverse events. The most commonly
      reported adverse events were nausea, dizziness, and somnolence. The mean change
      from baseline to endpoint in CAARS-Inv:SV total ADHD symptom score was -12.5 (P <
      0.001). A significant reduction in the CAARS-Inv:SV subscales (inattentive,
      hyperactive/impulsive, and ADHD index score, P < 0.001) was observed. DISCUSSION:
      This is the first atomoxetine clinical trial in adult patients with ADHD in
      China, Korea, and Taiwan. Atomoxetine was well tolerated in doses of up to 120
      mg/day with no unknown safety concerns.

PMID- 23857917
TI  - Imaging of extraradicular biofilm using combined scanning electron microscopy and
      stereomicroscopy.
AB  - Microorganisms are able to survive and induce persistent infection in
      extraradicular areas. The objective of this study was to evaluate the
      relationship between extraradicular biofilm and persistent periapical
      periodontitis. Thirty-five apical samples with different stages of pulp and
      periapical pathology (vital pulp, pulp necrosis without radiographically visible
      periapical lesions, chronic periapical periodontitis that had not received root
      canal therapy and persistent periapical periodontitis) were initially evaluated
      using scanning electron microscopy. The same samples were then processed using
      Brown and Brenn-modified Gram staining. We detected extraradicular biofilm in all
      samples with persistent periapical periodontitis and in three samples with
      chronic periapical periodontitis. The extraradicular bacteria predominantly had
      rod and filament morphology and were surrounded by varying amounts of amorphous
      extracellular material. The surfaces outside the root of the apical samples with
      vital pulp and pulp necrosis were covered by fibers, and no extraradicular
      microorganisms were present, which suggests that extraradicular biofilm is
      closely associated with failed endodontic treatments, thus resulting in
      persistent infection.

PMID- 23857918
TI  - Preparative enantioseparation of propafenone by counter-current chromatography
      using di-n-butyl L-tartrate combined with boric acid as the chiral selector.
AB  - This paper extends the research of the utilization of borate coordination
      complexes in chiral separation by counter-current chromatography (CCC). Racemic
      propafenone was successfully enantioseparated by CCC with di-n-butyl l-tartrate
      combined with boric acid as the chiral selector. The two-phase solvent system was
      composed of chloroform/ 0.05 mol/L acetate buffer pH 3.4 containing 0.10 mol/L
      boric acid (1:1, v/v), in which 0.10 mol/L di-n-butyl l-tartrate was added in the
      organic phase. The influence of factors in the enantioseparation of propafenone
      were investigated and optimized. A total of 92 mg of racemic propafenone was
      completely enantioseparated using high-speed CCC in a single run, yielding 40-42
      mg of (R)- and (S)-propafenone enantiomers with an HPLC purity over 90-95%. The
      recovery for propafenone enantiomers from fractions of CCC was in the range of 85
      90%. 

PMID- 23857922
TI  - Do the letters F, A and S represent Indonesian letter fluency stimuli?
AB  - INTRODUCTION: The letters F, A and S, originally used in the English letter
      fluency stimuli test, have been frequently adopted to assess executive function
      in many languages. However, few studies reported the significance of FAS testing
      employed in different languages. The current study explored whether FAS could be
      widely applied to the Indonesian language. METHODS: A total of 211 undergraduate
      students from state and private universities who participated in this study were
      randomly assigned into four groups. Each group was exposed to six different
      letter fluency stimuli. The total number of words the participants produced for
      each letter stimulus were averaged and ranked to determine the degree of
      difficulty in generating words. Furthermore, the normal distribution and equal
      ratio comparison were examined to verify the representative letter fluency
      stimuli. In addition, the effect of sex and university affiliation on letter
      fluency performance was also analyzed. RESULTS: The letters A and S were among
      the easiest letters used to generate words; however, the letter F was regarded as
      a difficult stimulus. Furthermore, only the number of words beginning the letter
      S was distributed according to a normal curve. The number of words starting with
      the letters F and A were not normally distributed. Although sex difference was
      not associated with letter fluency performance, difference in university
      affiliation showed a significant effect on performance. DISCUSSION: Our findings
      suggest that consideration of several stimuli factors is required to accurately
      measure performance in the letter fluency task in a specific language.

PMID- 23857923
TI  - Physical activity program preferences and perspectives of older adults with and
      without cognitive impairment.
AB  - INTRODUCTION: There is increasing evidence to support the benefits of physical
      activity on cognition in older adults. This paper describes (i) the attitudes,
      beliefs and barriers towards physical activity of older adults with and without
      cognitive impairment and (ii) their opinion of the attributes of the ideal
      physical activity program. METHODS: Thematic analysis of focus groups and
      individual interviews with 50 older adults with no cognitive impairment,
      subjective memory complaints, mild cognitive impairment and Alzheimer's disease
      was performed. RESULTS: Consistent with previous research in cognitively intact
      older adults, most participants, irrespective of cognitive status, had a positive
      attitude towards physical activity and believed it was beneficial both generally
      and for cognition. There was a preference for physical activity programs to be
      suggested by advertising and general practitioners (GPs), undertaken in a group
      setting, and beliefs that they should be tailored to individual's needs and
      preferences, and should be affordable according to their income. Participants
      with cognitive impairment cited specific barriers including "memory" and "lack of
      companion" as well as preferring "accessible" settings and "simple/light/safe"
      activities. DISCUSSION: These findings provide useful data, particularly from
      participants with cognitive impairment, with whom there has been little research
      to date. This could contribute to efforts to translate the growing research
      evidence of the benefits of physical activity for brain health into effective
      community programs.

PMID- 23857924
TI  - Resistance to agricultural biotechnology: the importance of distinguishing
      between weak and strong public attitudes.
AB  - Empirical research shows that European governments and retailers are unlikely to
      be directly punished by taxpayers and consumers if they move away from their anti
      GMO positions and policies. However, it is ultimately not the weak attitudes of
      taxpayers and consumers that matter to governments and retailers but the strong
      attitudes of the noisy anti-biotech movement. (Image: Highway signs: (c)maxmitzu 
      Fotolia.com; woman and balance: (c)lassedesignen - Fotolia.com). 

PMID- 23857925
TI  - Are people who still have their natural teeth willing to pay for mandibular two
      implant overdentures?
AB  - AIM: Oral health in Canada and most developed and developing countries is funded
      by private payers, whose acceptance of treatment depends on their valuation of
      it. This study aims to determine how dentate individuals in Quebec, Canada, would
      value the benefits of mandibular two-implant overdentures based on their
      willingness to pay (WTP) for the treatment, either directly or with
      insurance/government coverage. METHODS: A total of 39 individuals (23-54 years)
      completed a Web-based WTP survey that consisted of three cost scenarios: (a) out
      of-pocket payment; (b) private dental insurance coverage; and (c) public funding
      through additional taxes. Variations in WTP amounts were measured using
      regression models. RESULTS: Among respondents who were dentate or missing some
      teeth, average WTP out of pocket for implant overdentures was CAD$5419 for a 90%
      success rate. They were willing to pay an average CAD$169 as one-time payment for
      private dental insurance, with a one in five chance of becoming edentate. WTP
      amounts increased substantially with the probability of success of implant
      overdenture therapy. The results of regression analyses were consistent with
      theoretical predictions for education level and income (P < 0.05). CONCLUSIONS:
      The results of this study, within its limitations, suggest that dentate
      individuals would be willing to pay a significant amount to receive mandibular
      two-implant overdentures if and when they become edentate.

PMID- 23857926
TI  - Hepatitis C virus infection is independently associated with depression among
      methadone maintenance treatment heroin users in China.
AB  - INTRODUCTION: Depression and hepatitis C virus (HCV) infection are two common
      conditions among heroin users in methadone maintenance treatment (MMT). However,
      the comorbid relationship between depression and HCV infection among MMT patients
      is not well understood. METHODS: One hundred and fifteen MMT patients were
      recruited from the Yangpu MMT Clinic in Shanghai. Demographic characteristics,
      drug use and HCV-related information were collected using a structured interview.
      The Beck Depression Inventory (BDI-II) and the Perceived Stress Scale (PSS) were
      administered to evaluate participants' symptoms of depression and stress
      severity. HCV antibody (anti-HCV) test results were collected from patients' MMT
      clinical medical records. RESULTS: 58.2% of participants were anti-HCV positive,
      and 41.3% scored moderate-to-severe for symptoms of depression (BDI-II scores
      >19). The prevalence of depressive symptoms (BDI-II score >19) was greater in HCV
      positive than HCV negative participants (51.6% versus 27.7%, respectively; P =
      0.02). There was no significant difference in the perceived stress level by anti
      HCV status; overall, the perceived stress level score was 15.9 +/- 5.7. In
      logistic regression analysis, positive anti-HCV status (OR = 3.75, 95% CI = 1.42
      9.90), and greater perceived stress (OR = 1.23, 95% CI = 1.11-1.36) were
      independently associated with depression, after controlling for gender, age,
      duration of drug use and the awareness of HCV infection. DISCUSSION: Depression
      and HCV infection are common and co-occurring among MMT patients in Shanghai. HCV
      infection itself appears to be associated with depressive symptoms regardless of
      whether the individual is aware of his HCV infection status. This finding
      indicates that it is important to consider the impact of depressive symptoms on
      injection risk behaviors and HCV transmission when planning intervention programs
      in MMT clinics.

PMID- 23857927
TI  - Investigation of monomeric and oligomeric wine stilbenoids in red wines by ultra
      high-performance liquid chromatography/electrospray ionization quadrupole time-of
      flight mass spectrometry.
AB  - RATIONALE: Stilbenoids are secondary plant metabolites responsible for the
      protection of multiple plant species including grape vine from bacterial and
      fungal infection. Red wine has been shown to be a major source of these compounds
      in the human diet, where they display an array of health benefits. Providing a
      more complete profile of the stilbenoids present in red wine, this study detects
      41 stilbenoid compounds, 23 of which have never before been detected in red wine.
      METHODS: Red wine extracts were scanned using an ultra-high-performance liquid
      chromatograph coupled to a hybrid quadrupole time-of-flight mass analyzer.
      Multiple targeted MS/MS precursor ion scan experiments were performed using
      electrospray ionization operated in negative mode. Precursor ion masses were
      scanned for the monomeric and oligomeric stilbenoids, as well as modifications
      such as O-glycosylation, methoxylation and oxidation products of these compounds.
      Accurate mass precursor and characteristic product ions afforded partial
      structural elucidation and assignment of these compounds. RESULTS: A total of 41
      (both known and novel) stilbenoids were detected in extracted red wine. In
      addition to the well-known monomeric stilbenes, several resveratrol-resveratrol
      homodimers (m/z 453.1344), resveratrol-piceatannol heterodimers (m/z 469.1293)
      and piceatannol-piceatannol homodimers (m/z 485.1236) were detected. Modified
      dimers of resveratrol including O-glycosylated (m/z 615.1872), methoxylated (m/z
      485.1606) and oxidized (m/z 471.1449) dimers were also detected. Multiple trimers
      of resveratrol (m/z 679.1978) were detected for the first time in red wine, as
      well as some known and some novel stilbenoid tetramers (m/z 905.2604).
      CONCLUSIONS: In summary, 41 stilbenoids were detected in red wine, 23 for the
      first time. Both monomeric and oligomeric stilbenoids were partially identified
      and assigned by their accurate mass precursor ions and characteristic stilbenoid
      fragmentation patterns. Knowledge gained from these experiments contributes to a
      more complete understanding of the origin of the beneficial properties of red
      wine.

PMID- 23857928
TI  - Chemical analysis and chemical imaging of fragrances and volatile compounds by
      low-temperature plasma ionization mass spectrometry.
AB  - RATIONALE: The rapid analysis of volatile compounds, such as fragrances, is
      important in many commercial industries. The various ambient ionization methods
      have until now been largely applied to non-volatile or low-volatile compounds
      with success, and this study develops a semi-quantitative method for volatile
      compounds in commercial cleaning products. METHODS: Low-temperature plasma (LTP)
      ionization was used to perform rapid analysis, determine limits of detection
      (LODs) and perform chemical imaging on eight fragrances. Several mass analyzers
      including an ion trap, a quadrupole and an orbitrap were used to rapidly screen
      volatile compounds from cloth, paper, and glass and determine compositions
      present in a commercial cleaning product. Peltier cooling was used in some cases
      to enhance the retention time of compounds on a surface. RESULTS: This LTP method
      allowed the detection of fragrances in low picogram absolute amounts from glass,
      paper and cloth. Quantitation was demonstrated for compounds in a commercial
      cleaning product 1 min after the product was applied to a vinyl tile surface.
      High-throughput analysis and simultaneous detection of multiple compounds in a
      mixture were demonstrated with analysis times of less than 1 min. Modest spatial
      resolution (better than 1 cm) was achieved with LTP ionization. CONCLUSIONS: A
      semi-quantitative method has been demonstrated for the routine analysis of
      volatile and semi-volatile compounds. This method would be useful in quality
      control and production environments to determine product persistence, location of
      analytes and to complement olfactory studies for determining concentrations in
      the ambient environment.

PMID- 23857929
TI  - Use of 1,5-diaminonaphthalene to combine matrix-assisted laser
      desorption/ionization in-source decay fragmentation with hydrogen/deuterium
      exchange.
AB  - RATIONALE: In-Source Decay (ISD) in Matrix-Assisted Laser Desorption/Ionization
      (MALDI) mass spectrometry is a fast and easy top-down activation method. Our
      objective is to find a suitable matrix to locate the deuterons following in
      solution hydrogen/deuterium exchange (HDX). This matrix must circumvent the
      commonly encountered undesired back-exchange reactions, in order to preserve the
      regioselective deuteration pattern. METHODS: The 1,5-diaminonaphthalene (1,5-DAN)
      matrix is known to be suitable for MALDI-ISD fragmentation. MALDI Mass
      Spectrometry Imaging (MSI) was employed to compare 1,5-DAN and other commonly
      used MALDI matrices with respect to the extent of back-exchange and the
      uniformity of the H/D exchange profiles within the MALDI spots. We tested the
      back-exchange on the highly sensitive amyloid-beta peptide (1-40), and proved the
      regioselectivity on ubiquitin and beta-endorphin. RESULTS: MALDI-MSI results show
      that 1,5-DAN leads to the least back-exchange over all the spot. MALDI-ISD
      fragmentation combined with H/D exchange using 1,5-DAN matrix was validated by
      localizing deuterons in native ubiquitin. Results agree with previous data
      obtained by Nuclear Magnetic Resonance (NMR) and Electron Transfer Dissociation
      (ETD). Moreover, 1,5-DAN matrix was used to study the H/D exchange profile of the
      methanol-induced helical structure of beta-endorphin, and the relative protection
      can be explained by the polarity of residues involved in hydrogen bond formation.
      CONCLUSIONS: We found that controlling crystallization is the most important
      parameter when combining H/D exchange with MALDI. The 1,5-DAN matrix is
      characterized by a fast crystallization kinetics, and therefore gives robust and
      reliable H/D exchange profiles using MALDI-ISD.

PMID- 23857930
TI  - Measurement of multiply substituted isotopologues ('clumped isotopes') of CO2
      using a 5 kV compact isotope ratio mass spectrometer: performance, reference
      frame, and carbonate paleothermometry.
AB  - RATIONALE: The burgeoning field of 'clumped isotope' paleothermometry, which has
      broad applications in geosciences, depends almost entirely on measurements made
      on two types of mass spectrometer with the same ion source design. Demonstration
      that these measurements can be carried out on a retrofitted mass spectrometer
      with a different type of ion source is important to the growing community of
      geoscientists considering employing this technique. METHODS: We summarize the
      sample preparation techniques, mass spectrometry, and data processing involved in
      establishing an absolute reference frame for the measurement of Delta47 in CO2
      from carbonate minerals using a prototype 5 kV mass spectrometer. The prototype
      differs from previously marketed mass spectrometers only in the presence of six
      extra Faraday cups designed specifically to measure ion beams of masses 44-49. We
      employ pressure baseline corrections on the small mass 47 signal. RESULTS: The
      system was fully capable of establishing absolute reference frames for clumped
      isotope carbonate paleothermometry, despite alternative use of the system for
      other types of measurements (carbonate delta(18)O and delta(13)C values, water
      delta(18)O and delta(2)H values via equilibration, and delta(13) C and delta(15)N
      values of sedimentary organic material) in different reference frames. Repeated
      measurements of CO2 from carbonate standards yielded external precisions
      comparable with those from other laboratories and adequate for paleothermometry
      to a precision of near or below +/-5  degrees C. The accuracy was demonstrated by
      reasonable temperatures being obtained for different types of repeatedly measured
      carbonates. Measurements of the pressure baseline with every sample increased
      analysis times by 20 min, but decreased the stabilization time of the reference
      frame by days to weeks, while improving precision. CONCLUSIONS: Simple
      modifications to existing instrumentation will allow more laboratories to perform
      clumped isotope measurements. The prototype mass spectrometer used herein
      provides precision comparable with all published data. We show that, where
      negatively charged species are associated with large ion beams, making pressure
      baseline corrections with every measurement is increasingly important no matter
      what instrument is used.

PMID- 23857931
TI  - Formation of odd-electron product ions in collision-induced fragmentation of
      electrospray-generated protonated cathinone derivatives: aryl alpha-primary amino
      ketones.
AB  - RATIONALE: Modification of the even-electron rule for fragmentation reactions of
      protonated molecules (even electron ions) may be necessary to interpret the
      liquid chromatography/mass spectrometry (LC/MS) spectra of aryl alpha-primary
      amino ketones as new designer drugs. METHODS: Collision-induced fragmentation of
      38 protonated cathinone derivatives generated by electrospray ionisation (ESI)
      was examined by hybrid quadrupole time-of-flight mass spectrometry (Q-TOF MS).
      RESULTS: Q-TOF MS revealed that odd-electron product ions are often formed by
      collision-induced dissociation (CID) of protonated aryl alpha-primary amino
      ketones, contradicting the even-electron rule. Radical cations were among the
      most characteristic and most abundant ions in the CID-MS/MS product spectra, and
      were usually represented by basic peaks in the spectra. CONCLUSIONS: To help
      elucidate the correct structures of new aryl alpha-primary amino ketone drugs by
      LC/MS/MS, it is essential to include odd-electron product ions in the data
      interpretation rules. Even and odd numbers of valence electrons in the product
      ions should be allowed in data interpretation.

PMID- 23857932
TI  - Infrared multiple photon dissociation spectroscopy of group I and group II metal
      complexes with Boc-hydroxylamine.
AB  - RATIONALE: Hydroxamates are essential growth factors for some microbes, acting
      primarily as siderophores that solubilize iron for transport into a cell. Here we
      determined the intrinsic structure of 1:1 complexes between Boc-protected
      hydroxylamine and group I ([M(L)](+)) and group II ([M(L-H)](+)) cations, where M
      and L are the cation and ligand, respectively, which are convenient models for
      the functional unit of hydroxamate siderphores. METHODS: The relevant complex
      ions were generated by electrospray ionization (ESI) and isolated and stored in a
      Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Infrared
      spectra of the isolated complexes were collected by monitoring (infrared)
      photodissociation yield as a function of photon energy. Experimental spectra were
      then compared to those predicted by density functional theory (DFT) calculations.
      RESULTS: The infrared multiple photon dissociation (IRMPD) spectra collected are
      in good agreement with those predicted to be lowest-energy by DFT. The spectra
      for the group I complexes contain six resolved absorptions that can be attributed
      to amide I and II type and hydroxylamine N-OH vibrations. Similar absorptions are
      observed for the group II cation complexes, with shifts of the amide I and amide
      II vibrations due to the change in structure with deprotonation of the
      hydroxylamine group. CONCLUSIONS: IRMPD spectroscopy unequivocally shows that the
      intrinsic binding mode for the group I cations involves the O atoms of the amide
      carbonyl and hydroxylamine groups of Boc-hydroxylamine. A similar binding mode is
      preferred for the group II cations, except that in this case the metal ion is
      coordinated by the O atom of the deprotonated hydroxylamine group.

PMID- 23857933
TI  - Oxygen isotope analyses of biogenic opal and quartz using a novel
      microfluorination technique.
AB  - RATIONALE: Measuring delta(18)O values in silicates is difficult and hazardous in
      comparison with measurements of carbonate minerals due to the difficulty in
      breaking Si-O-Si bonds. A novel method for measurement of delta(18)O values from
      quartz and biogenic silica utilizing high-temperature pyrolysis with continuous
      flow isotope ratio mass spectrometry (CF-IRMS) is presented. METHODS: Samples
      were prepared by offline dehydroxylation/dehydration under vacuum at 1060 degrees
      C. The dehydroxylated samples are mixed with polytetrafluoroethylene (PTFE)
      powder (2.3:1 PTFE/Si) and graphite in silver foil capsules and reacted in a
      vario PYRO cube TC/EA system in a glassy carbon reaction tube. Quartz and
      biogenic opal samples react with available carbon in a microfluorination
      environment upon decomposition of the PTFE, producing CO for analysis via CF
      IRMS. RESULTS: Silicate samples reacted quantitatively, producing data with
      yields >=88% from ~400 ug samples. Multiple analyses with international standards
      demonstrated accuracy for replicate measurements (1sigma range +/-0.3-0.60/00),
      comparing favorably with previously published techniques. CONCLUSIONS: New data
      produced with the microfluorination technique are comparable with data from
      studies using existing methodologies. The microfluorination technique has the
      potential to greatly increase the number of laboratories producing silicate
      oxygen isotope data for mineralogic, paleoclimatic and biogeochemical
      applications.

PMID- 23857934
TI  - Addressing the need for biomarker liquid chromatography/mass spectrometry assays:
      a protocol for effective method development for the bioanalysis of endogenous
      compounds in cerebrospinal fluid.
AB  - RATIONALE: Research on disorders of the central nervous system (CNS) has shown
      that an imbalance in the levels of specific endogenous neurotransmitters may
      underlie certain CNS diseases. These alterations in neurotransmitter levels may
      provide insight into pathophysiology, but can also serve as disease and
      pharmacodynamic biomarkers. To measure these potential biomarkers in vivo, the
      relevant sample matrix is cerebrospinal fluid (CSF), which is in equilibrium with
      the brain's interstitial fluid and circulates through the ventricular system of
      the brain and spinal cord. Accurate analysis of these potential biomarkers can be
      challenging due to low CSF sample volume, low analyte levels, and potential
      interferences from other endogenous compounds. METHODS: A protocol has been
      established for effective method development of bioanalytical assays for
      endogenous compounds in CSF. Database searches and standard-addition experiments
      are employed to qualify sample preparation and specificity of the detection thus
      evaluating accuracy and precision. RESULTS: This protocol was applied to the
      study of the histaminergic neurotransmitter system and the analysis of histamine
      and its metabolite 1-methylhistamine in rat CSF. CONCLUSIONS: The protocol
      resulted in a specific and sensitive novel method utilizing pre-column
      derivatization ultra high performance liquid chromatography/tandem mass
      spectrometry (UHPLC/MS/MS), which is also capable of separating an endogenous
      interfering compound, identified as taurine, from the analytes of interest.

PMID- 23857935
TI  - Side reactions in protein cross-linking experiments using azide linkers.

PMID- 23857936
TI  - MRT letter: a total variation based method for 3D shape recovery of microscopic
      objects through image focus.
AB  - Generally, shape from focus methods use a single focus measure to compute focus
      quality and to obtain an initial depth map of an object. However, different focus
      measures perform differently in diverse conditions. Therefore, it is hard to get
      accurate 3D shape based on a single focus measure. In this article, we propose a
      total variation based method for recovering 3D shape of an object by combining
      multiple depth hypothesis obtained through different focus measures. Improved
      performance of the proposed method is evaluated by conducting several experiments
      using images of synthetic and real microscopic objects. Comparative analysis
      demonstrates the effectiveness of the proposed approach.

PMID- 23857937
TI  - Palladium- and ruthenium-catalyzed cycloisomerization of enynamides and
      enynhydrazides: a rapid approach to diverse azacyclic frameworks.

PMID- 23857938
TI  - Overview of psychiatric scales used in Nepal: their reliability, validity and
      cultural appropriateness.
AB  - A review of the Western mental health scales that have been utilized in Nepal was
      conducted. Academic search engines (PubMed, MEDLINE, PsychLIT, Social Sciences
      Citation Index, and Anthropology Plus) were searched using relevant terms for the
      years 1990-2011. Search results indicated a limited number of mental health
      scales had been used and/or developed in Nepal with mixed emphasis on reliability
      and validity, as well as cultural considerations. These scales, methods and
      limitations are discussed within the cultural and social background of Nepal. 

PMID- 23857939
TI  - Distressed personality without a partner enhances the risk of depression in
      patients with coronary heart disease.
AB  - INTRODUCTION: Cultural differences in the combined effects of Type D personality
      and other mediating factors in the Asian population have not been reported. We
      examined the influence of the Type D personality in relation to the presence of a
      partner by measuring symptoms of anxiety and depression, quality of life, self
      perception of health status in coronary heart disease (CHD) patients and normal
      controls. METHODS: Normal controls (n = 541) and patients with CHD (n = 110) were
      included. All participants completed self-report measures on Type D personality,
      questionnaires on socio-demographic factors, the Spielberger State and Trait
      Anxiety Inventory-State (STAI-S), and the Center for Epidemiologic Studies
      Depression Scale (CES-D). By stratifying participant group, personality type, and
      partner status, eight groups were constructed. RESULTS: The subjects with Type D
      personality showed higher mean scores on the STAI-S and CES-D as well as
      perception of their health. In cases of depression, CHD patients with Type D
      personality and without partner showed about a 50-fold increase in odds ratio
      when compared with non-Type D normal controls with partners. Odds ratio for
      depression changed from 31.44 to 48.72 in CHD patients with Type D personality
      based on the existence of a partner. DISCUSSION: Having a partner significantly
      predicted the risk of depression. It is important to identify social support
      systems in CHD patients with Type D personality.

PMID- 23857940
TI  - Analytical study of a new turbidimetric assay for urinary neutrophil gelatinase
      associated lipocalin (NGAL) determination.

PMID- 23857941
TI  - Prenatal diagnosis of haemophilia: our experience of 44 cases.
AB  - BACKGROUND: Haemophilia A and B (HA, HB) are the most frequent X-linked bleeding
      diseases; two-thirds of cases are severe. METHODS: We counselled 51 couples for
      prenatal diagnosis (PD) of haemophilia. In 7/51 (13.7%) cases, the couple decided
      not to undergo PD because counselling revealed that they were carriers of a mild
      form of the disease, while we performed 44 PD for severe HA (36 cases) or HB (8
      cases). The indication for PD was a haemophilic child (30/44, 68.2%) or an
      affected family member (12/44, 27.3%); in two cases the non-carrier mother of
      isolated haemophilic patients requested PD because of the risk of mosaicism.
      RESULTS: We completed PD in 43/44 cases; in one case, the prenatal sample was
      contaminated by maternal DNA; however, molecular analysis revealed the female sex
      of the foetus. We performed PD for 16 of the 36 couples at risk of HA (44.4%) by
      analysing the intron (IVS)22 inversion; in 1/36 cases (2.8%) the mother had the
      IVS1 inversion, and in 8/36 (22.2%) the family mutation was identified by
      sequencing; in 11/36 (30.6%) cases the family mutation was unknown, and PD was
      performed by linkage (no recombination nor uninformative cases occurred). For HB,
      in 6/8 (75.0%) cases, PD was performed by DHPLC or by sequencing; in 2/8 cases we
      tested intragenic markers (again with no cases of recombination or uninformative
      families). CONCLUSIONS: PD in well-equipped laboratories, and multidisciplinary
      counselling are an aid to planning reproductive and early therapeutic strategies
      in families with severe haemophilia.

PMID- 23857942
TI  - Zopolrestat as a human glyoxalase I inhibitor and its structural basis.

PMID- 23857943
TI  - Efficacy of Williams LifeSkills training for improving psychological health: a
      pilot comparison study of Chinese medical students.
AB  - INTRODUCTION: High stress levels and mental health problems are common among
      medical students. Behavioral interventions aimed at preventing mental health
      problems among medical students have been recommended in managing stress during
      their study period. The aim of the study was to evaluate the efficacy of Williams
      LifeSkills training (WLST) for improving psychological health of Chinese medical
      students. METHODS: Sixty medical students were chosen as the study group (n = 30)
      and the control group (n = 30). The study group completed the 8-week WLST, while
      the controls did not take any training course. All subjects were assessed before
      and after the 8-week training period using the Self-Rating Anxiety Scale (SAS),
      Self-Rating Depression Scale (SDS), Trait Coping Style Questionnaire (TCSQ),
      Interpersonal Support Evaluation List (ISEL) and Self-Esteem Scale (SES). The
      data of 29 students in the study group and 26 students in the control group were
      qualified for statistical analysis in the current study. RESULTS: Group-time
      interactions were significant for the ISEL total (P = 0.008), ISEL appraisal (P =
      0.002), SES (P = 0.002), SAS (P = 0.005) and SDS (P = 0.032). Post-hoc paired
      Student's t-tests showed that all these measures improved significantly (P <
      0.05) in the study group but were unchanged in the control group. DISCUSSION: In
      our study, a behavioral intervention - WLST - improved psychological health of
      the study group. If confirmed in further trials, these results suggest that WLST
      could be a means of improving mental health of medical students as well as other
      groups in China.

PMID- 23857944
TI  - Biochemical and molecular mechanisms for the association between obesity, chronic
      inflammation, and breast cancer.
AB  - Upper body obesity is a risk factor for postmenopausal breast cancer and is
      related to an aggressive tumor phenotype and a poor prognosis regardless of
      menopausal status. After the menopause, the major mechanism for the association
      with disease risk is elevated estrogen production by adipose tissue, due to a
      high level of aromatase activity: these hormone-dependent tumors express both
      estrogen and progesterone receptors. Other important biological factors of risk
      include leptin and adiponectin, adipokines with opposing endocrine and paracrine
      activities, and obesity-related hyperinsulinemia. Chronic inflammation of the
      breast adipose tissue, which occurs in some obese women and is indicated by the
      accumulation of macrophages around dead adipocytes ("crown-like structures"),
      rather than adiposity per se, may prove to be the pathological lesion responsible
      for both local aromatase induction, and enhanced invasiveness and metastatic
      capacity through biological mechanisms that involve leptin, tumor necrosis factor
      alpha, and insulin. A causal association between obesity in premenopausal women
      and breast cell epithelial-mesenchymal transition, perhaps with the participation
      of the Wnt signaling pathway, and aggressive hormone-independent breast cancer is
      suggested by a number of experimental and clinical studies.

PMID- 23857945
TI  - Late diagnosis of double aortic arch: consequences on long-term follow-up.
AB  - Double aortic arch is the most common congenital anomaly of the aortic arch
      system, in which the trachea and esophagus are completely encircled by vascular
      segments of the aortic arch and its branches, often resulting in variable airway
      compression. One case of late diagnosis of this congenital malformation and long
      term consequences of late surgical treatment with persistent tracheo
      broncomalacia and dynamic airway obstruction is reported. This report emphasizes
      the importance of an early diagnosis to minimise the progressive airways damage
      and subsequent respiratory symptoms, that need an accurate medical follow-up.

PMID- 23857946
TI  - Nanoprofiles evaluation of ZnO thin films by an evanescent light method.
AB  - The extraction efficiency of evanescent light from ZnO nanolayers and their
      thickness profiles in the range of (1-105) nm was evaluated by a new microscopy
      technique, differential evanescent light intensity imaging method. It is based on
      capturing the evanescent light scattered by the layer of the material deposited
      on glass substrates. The analyzed ZnO films were obtained by pulsed laser
      deposition at 27 degrees C and 100 degrees C, using a nanosecond UV laser source.

PMID- 23857947
TI  - To BNP or not to BNP.

PMID- 23857948
TI  - Palladium-catalyzed three-component reaction of allenes, aryl iodides, and diazo
      compounds: approach to 1,3-dienes.

PMID- 23857950
TI  - The impact on midlevel vision of statistically optimal divisive normalization in
      V1.
AB  - The first two areas of the primate visual cortex (V1, V2) provide a paradigmatic
      example of hierarchical computation in the brain. However, neither the functional
      properties of V2 nor the interactions between the two areas are well understood.
      One key aspect is that the statistics of the inputs received by V2 depend on the
      nonlinear response properties of V1. Here, we focused on divisive normalization,
      a canonical nonlinear computation that is observed in many neural areas and
      modalities. We simulated V1 responses with (and without) different forms of
      surround normalization derived from statistical models of natural scenes,
      including canonical normalization and a statistically optimal extension that
      accounted for image nonhomogeneities. The statistics of the V1 population
      responses differed markedly across models. We then addressed how V2 receptive
      fields pool the responses of V1 model units with different tuning. We assumed
      this is achieved by learning without supervision a linear representation that
      removes correlations, which could be accomplished with principal component
      analysis. This approach revealed V2-like feature selectivity when we used the
      optimal normalization and, to a lesser extent, the canonical one but not in the
      absence of both. We compared the resulting two-stage models on two perceptual
      tasks; while models encompassing V1 surround normalization performed better at
      object recognition, only statistically optimal normalization provided systematic
      advantages in a task more closely matched to midlevel vision, namely
      figure/ground judgment. Our results suggest that experiments probing midlevel
      areas might benefit from using stimuli designed to engage the computations that
      characterize V1 optimality. 

PMID- 23857951
TI  - Orientation-crowding within contours.
AB  - We examined how crowding (the breakdown of object recognition in the periphery
      caused by interference from "clutter") depends on the global arrangement of
      target and distracting flanker elements. Specifically we probed orientation
      discrimination using a near-vertical target Gabor flanked by two vertical
      distractor Gabors (one above and one below the target). By applying variable
      (opposite-sign) horizontal offsets to the positions of the two flankers we
      arranged the elements so that on some trials they formed contours with the target
      and on others they did not. While the presence of flankers generally elevated
      orientation discrimination thresholds for the target we observe maximal crowding
      not when flanker and targets were co-aligned but when a small spatial offset was
      applied to flanker location, so that contours formed between flanker and targets
      only when the target orientation was cued. We also report that observers'
      orientation judgments are biased, with target orientation appearing either
      attracted or repulsed by the global/contour orientation. A second experiment
      reveals that the sign of this effect is dependent both on observer and on
      eccentricity. In general, the magnitude of repulsion is reduced with eccentricity
      but whether this becomes attraction (of element orientation to contour
      orientation) is dependent on observer. We note however that across observers and
      eccentricities, the magnitude of repulsion correlates positively with the amount
      of release from crowding observed with co-aligned targets and flankers,
      supporting the notion of fluctuating bias as the basis for elevated crowding
      within contours. 

PMID- 23857949
TI  - Adaptation to blurred and sharpened video.
AB  - The visual system can distinguish different levels of blur and different levels
      of excess sharpness. Adaptation alters this capacity so that the adapted blur (or
      sharp) level looks more like a normal, properly focused image. Here, we describe
      the more general pattern of aftereffects of blur and sharp adaptation by
      measuring matching functions, using video clips from a DVD movie as stimuli.
      Results show that blur and sharp adaptation are selective: The sharpening
      aftereffects of blur adaptation are strongest for blurry videos while the
      blurring aftereffects of sharp adaptation are strongest for sharp videos. Despite
      the spatiotemporal variability of our adaptor and test stimuli, we found
      adaptation effects similar in magnitude to previous studies using invariant
      static images. A recent model of blur adaptation can be simplified to explain the
      form of our data, leading us to conclude that what we see as blur/sharp
      adaptation is a consequence of narrowband contrast adaptation. 

PMID- 23857952
TI  - Teachers of Psychiatry meeting on evaluation to improve quality of research, held
      in Shanghai, China, organized by the Pacific Rim College of Psychiatrists.

PMID- 23857953
TI  - Suicidal and help-seeking behavior in Xiamen, south China.
AB  - INTRODUCTION: The aim of this study is to examine the association between
      suicidal behavior and mental health status of south Chinese people, and explore
      the mediating effect of help-seeking behaviors. METHODS: The study participants
      were 10,757 persons aged 18 years and older from the mental health survey of
      Xiamen city. Data on suicidal behavior and help-seeking behavior were collected
      by trained psychiatric nurses through face-to-face interviews. Mental health
      status was assessed using the 12-item General Health Questionnaire (GHQ-12).
      Multiple logistic regression and general linear model were used in statistical
      analysis. RESULTS: In the entire study sample, 236 study participants reported
      suicide ideation (2.19%, 95% CI: 1.92-2.47%), and 59 reported at least one
      suicide attempt (0.55%, 95% CI: 0.41-0.69%). Individuals with suicide attempt and
      suicide ideation had higher GHQ scores than those without suicidal behavior. The
      majority of study participants with suicide ideation or suicide attempt did not
      seek any help (77.5% and 79.7%, respectively). Among participants with suicidal
      behavior, seeking help from mental health professional was associated with a
      better mental health status (OR = 4.04, 95%CI: 1.17-10.16). DISCUSSION: Only a
      small proportion of individuals with suicide behavior in south China had ever
      sought help. Seeking help was associated with a better mental health status.

PMID- 23857954
TI  - A new strategy for the synthesis of iron-oxide nanocrystals by using a single
      spinneret electrospinning technique.
AB  - Iron-oxide nanocrystals (IONCs) have been widely researched, owing to their
      unique physical and chemical properties. Herein, a new strategy that involves an
      electrospinning technique with the addition of a surfactant is reported as an
      effective method for the fabrication of shaped IONCs. With the same precursor
      compositions, only iron-oxide nanoparticles were obtained by using a sol-gel
      method without electrospinning. However, when the electrospinning technique was
      introduced, IONCs with special geometrical shapes (e.g., octahedral) were
      obtained. Characterization data indicated that the IONCs were composed of
      magnetite (Fe3O4) and maghemite (gamma-Fe2O3), the ratio of which could be tuned
      by changing the concentration of the surfactants in the precursor solutions. A
      mechanism for the formation of IONCs is also proposed. The effect of surfactant
      on the decomposition of the iron complex is the main motivation for the formation
      of IONCs. In the sol-gel method without electrospinning, this effect is
      completely inhibited by the disturbance of long molecular chains. However, in the
      electrospinning strategy, such disturbance can be completely or partially
      diminished by the electrical force field during the electrospinning process and
      by the spatial effect of the nanofibers, thus leading to the formation of IONCs.
      Finally, the magnetic properties of the obtained IONCs were investigated. This
      strategy is versatile and environmentally friendly and it will be applicable to
      the synthesis of many other functional inorganic materials.

PMID- 23857955
TI  - Prevalence of and associations between body dysmorphic concerns, obsessive
      beliefs and social anxiety.
AB  - INTRODUCTION: Physical attractiveness has been of concern in different cultures
      and at different times. Physical attractiveness can influence one's thoughts and
      actions, and concerns regarding body image can be destructive, giving rise to
      psychological problems. The purpose of the present study was to determine the
      prevalence of body dysmorphic concerns, related sex differences and comorbidity
      with social anxiety and obsessive beliefs. METHOD: Using a stratified and cluster
      sampling procedure, 1,200 males and females were randomly selected. Self-report
      measures on body image, social anxiety and obsessive beliefs were distributed of
      which 843 completed questionnaires (54.9% males and 45.1% females) were returned
      (return rate of 70.25%). Therefore, data pertaining to 463 males and 380 females
      ranging in age from 17 to 20 years with a mean age of 18.12 years (SD = 1.06)
      were analyzed. RESULTS: Findings suggest a prevalence rate of 19.1% for body
      dysmorphic disorder, 23.6% for social anxiety and 8.8% for obsessive beliefs.
      Both social anxiety and obsessive beliefs were found to be comorbid with body
      dysmorphic concerns. The percentage of individuals reporting comorbid social
      anxiety (12.9%) was greater than that of those reporting comorbid obsessive
      beliefs (6.4%). Males with body dysmorphic concerns reported more obsessive
      beliefs (8.2% versus 4.1%), while their female counterparts reported more social
      anxiety (23.4% versus 4.2%). DISCUSSION: In males, body image concerns appear to
      be more cognitive in quality, while in females, body image concerns seem more
      emotional in tone. As the measures used do not yield formal diagnoses, findings
      should be viewed with caution.

PMID- 23857956
TI  - Gold-catalyzed tandem cycloisomerization/Cope rearrangement: an efficient access
      to the hydroazulenic motif.

PMID- 23857957
TI  - Association between morningness-eveningness and temperament and character in
      community-dwelling Korean adults.
AB  - INTRODUCTION: Previous studies have reported an association between biogenetic
      temperament/character and circadian preference in Spanish or French college
      students. Our aim is to investigate the association between temperament/character
      and circadian preference in psychiatrically healthy, community-dwelling Korean
      adults of a wide age range. METHODS: Subjects free of Axis I disorders (n = 342)
      completed the Morningness-Eveningness Questionnaire and the Temperament and
      Character Inventory. RESULTS: High Novelty Seeking and low Self-Directedness was
      associated with eveningness. In contrast to prior studies on college students,
      eveningness was associated with high (not low) Harm Avoidance. Eveningness
      Novelty Seeking association and Eveningness-Harm Avoidance association were
      prominent in females. Eveningness-Novelty Seeking was prominent in the older
      group (age >=40), while Eveningness-Harm Avoidance was prominent in the younger
      group (age <=40). DISCUSSION: Despite the limitation of the small sample size,
      the present study suggests that eveningness is associated with high Novelty
      Seeking/Harm Avoidance and low Self-Directedness in community-dwelling adults,
      and that this association may be related to age, gender, and other sociocultural
      factors.

PMID- 23857958
TI  - A simple prognostic scoring system for patients receiving transarterial
      embolisation for hepatocellular cancer.
AB  - BACKGROUND: The prognosis for patients with hepatocellular cancer (HCC)
      undergoing transarterial therapy (TACE/TAE) is variable. METHODS: We carried out
      Cox regression analysis of prognostic factors using a training dataset of 114
      patients treated with TACE/TAE. A simple prognostic score (PS) was developed,
      validated using an independent dataset of 167 patients and compared with Child
      Pugh, CLIP, Okuda, Barcelona Clinic Liver Cancer (BCLC) and MELD. RESULTS: Low
      albumin, high bilirubin or alpha-fetoprotein (AFP) and large tumour size were
      associated with a two- to threefold increase in the risk of death. Patients were
      assigned one point if albumin <36 g/dl, bilirubin >17 MUmol/l, AFP >400 ng/ml or
      size of dominant tumour >7 cm. The Hepatoma arterial-embolisation prognostic
      (HAP) score was calculated by summing these points. Patients were divided into
      four risk groups based on their HAP scores; HAP A, B, C and D (scores 0, 1, 2 and
      >2, respectively). The median survival for the groups A, B, C and D was 27.6,
      18.5, 9.0 and 3.6 months, respectively. The HAP score validated well with the
      independent dataset and performed better than other scoring systems in
      differentiating high- and low-risk groups. CONCLUSIONS: The HAP score predicts
      outcomes in patients with HCC undergoing TACE/TAE and may help guide treatment
      selection, allow stratification in clinical trials and facilitate meaningful
      comparisons across reported series.

PMID- 23857959
TI  - A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with
      paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer.
AB  - BACKGROUND: This phase I/II study examined the safety and efficacy of
      Sepantronium Bromide (S), a small-molecule selective survivin suppressant,
      administered in combination with carboplatin (C) and paclitaxel (P). PATIENTS AND
      METHODS: Forty-one patients were treated on study. Twenty-two patients received
      escalating doses of S (3.6-12 mg/m(2)) and 19 with untreated stage IV non-small
      cell lung cancer (NSCLC) were treated with the maximum tolerated dose of 10
      mg/m(2) in combination with standard doses of C (AUC6) and P (200 mg/m(2)) for
      six cycles. S was administered as a continuous intravenous infusion (CIVI) over
      72 h in 21-day treatment cycles. Study end points included safety and toxic
      effect, response rate, progression-free and overall survival (PFS and OS), as
      well as exploratory pharmacodynamic correlates. RESULTS: Treatment with S was
      well tolerated, and toxic effects were mostly hematological in the phase II
      study. Two (11%) partial responses were observed with a median PFS of 5.7 months
      and median OS 16.1 months. Pharmacodynamic analysis did not demonstrate an
      association with response. CONCLUSION: The combination of S (10 mg/m(2)/day 72-h
      CIVI) administered with C and P every 3 weeks exhibited a favorable safety
      profile but failed to demonstrate an improvement in response rate in advanced
      NSCLC. CLINICAL TRIAL NUMBER: NCT01100931.

PMID- 23857960
TI  - Circulating tumor cells predict progression-free and overall survival in Chinese
      patients with metastatic breast cancer, HER2-positive or triple-negative
      (CBCSG004): a multicenter, double-blind, prospective trial.
AB  - BACKGROUND: The aim of this multicenter, double-blind, prospective study was to
      evaluate the potential utility of circulating tumor cell (CTC) measurements in
      predicting responses to anticancer therapies, including response to human
      epidermal growth factor receptor-2 (HER-2)-targeted agents, progression-free
      survival (PFS), and overall survival (OS) in Chinese women with metastatic breast
      cancer (MBC). PATIENTS AND METHODS: Three hundred MBC patients planned to
      complete three CTC blood draws and two imaging studies. RESULTS: A total of 294
      of the 300 MBC patients enrolled from six leading Chinese cancer centers were
      assessable. In multivariate Cox regression analyses, the baseline CTC number
      remained an independent prognostic factor for PFS [hazard ratio (HR) = 1.93; 95%
      confidence interval (CI) = 1.39-2.69; P < 0.001) and OS (HR = 3.76; 95% CI = 2.35
      6.01; P < 0.001). Similar results were observed for CTC counts at the first
      follow-up visit for both PFS (P = 0.049) and OS (P < 0.001). CONCLUSIONS:
      Enumeration of CTCs in Chinese MBC patients provides substantial prognostic
      information and is an independent factor associated with PFS and OS. Moreover, we
      demonstrated the prognostic value in the various disease subtypes, including HER
      2-positive disease irrespective of therapy.

PMID- 23857961
TI  - Quality indicators in ovarian cancer surgery: report from the French Society of
      Gynecologic Oncology (Societe Francaise d'Oncologie Gynecologique, SFOG).
AB  - BACKGROUND: Based on registries, the European experience has been that <50% of
      patients are treated according to protocols and/or benefit from the minimum
      required surgery for ovarian cancer. The French Cancer Plan 2009-2013 considers
      the definition of qualitative indicators in ovarian cancer surgery in France.
      This endeavour was undertaken by the French Society of Gynaecologic Oncology
      (SFOG) in partnership with the French National College of Obstetricians and
      Gynecologists and all concerned learned societies in a multidisciplinary mindset.
      METHODS: The quality indicators for the initial management of patients with
      ovarian cancer were based on the standards of practice determined from scientific
      evidence or expert consensus. RESULTS: The indicators were divided into
      structural indicators, including material (equipment), human (number and
      qualification of staff), and organizational resources, process indicators, and
      outcome indicators. CONCLUSIONS: The enforcement of a quality assurance programme
      in any country would undoubtedly promote improvement in the quality of care for
      ovarian cancer patients and would result in a dramatic positive impact on their
      survival. Such a policy is not only beneficial to the patient, but is also
      profitable for the healthcare system.

PMID- 23857962
TI  - Dietary intake of acrylamide and pancreatic cancer risk in the European
      Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
AB  - BACKGROUND: In 1994, acrylamide (AA) was classified as a probable human
      carcinogen by the International Agency for Research on Cancer. In 2002, AA was
      discovered at relatively high concentrations in some starchy, plant-based foods
      cooked at high temperatures. PATIENTS AND METHODS: A prospective analysis was
      conducted to evaluate the association between the dietary intake of AA and ductal
      adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European
      Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox
      regression modeling. EPIC includes >500,000 men and women aged 35-75 at
      enrollment from 10 European countries. AA intake was estimated for each
      participant by combining questionnaire-based food consumption data with a
      harmonized AA database derived from the EU monitoring database of AA levels in
      foods, and evaluated in quintiles and continuously. RESULTS: After a mean follow
      up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were
      observed and included in the present analysis. At baseline, the mean dietary AA
      intake in EPIC was 26.22 ug/day. No overall association was found between
      continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95,
      95%CI:0.89-1.01 per 10 ug/day). There was no effect measure modification by
      smoking status, sex, diabetes, alcohol intake or geographic region. However,
      there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 ug/day)
      between AA intake and PC risk in obese persons as defined using the body mass
      index (BMI, >= 30 kg/m(2)), but not when body fatness was defined using waist and
      hip circumference or their ratio. CONCLUSIONS: Dietary intake of AA was not
      associated with an increased risk of PC in the EPIC cohort.

PMID- 23857963
TI  - Gd-doped BNNTs as T2-weighted MRI contrast agents.
AB  - This work describes, for the first time, doping of boron nitride nanotubes
      (BNNTs) with gadolinium (Gd@BNNTs), a stable functionalization that permits non
      invasive BNNT tracking via magnetic resonance imaging (MRI). We report the
      structure, Gd loading, and relaxometric properties in water suspension at 7 T of
      Gd@BNNTs, and show the behaviour of these nanostructures as promising T2-weighted
      contrast agents. Finally, we demonstrate their complete biocompatibility in vitro
      on human neuroblastoma cells, together with their ability to effectively label
      and affect contrast in MRI images at 7 T. 

PMID- 23857964
TI  - Selective application of a test based on risk: using limited resources wisely.

PMID- 23857965
TI  - Financial incentives in cancer care and impact on prescribing practice.

PMID- 23857967
TI  - Prospective multicenter study evaluating the survival of patients with locally
      advanced cervical cancer undergoing laparoscopic para-aortic lymphadenectomy
      before chemoradiotherapy in the era of positron emission tomography imaging.
AB  - PURPOSE: The aim of this prospective study conducted in three French
      comprehensive cancer centers was to evaluate the therapeutic impact on survival
      of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical
      cancer (LACC) before chemoradiotherapy. PATIENTS AND METHODS: We conducted a
      prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC
      with negative positron emission tomography (PET) imaging of the PA area and
      undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the
      PA area when PA nodes were involved. Chemoradiotherapy modalities were
      homogeneous across institutions. Patients with a poor prognosis histologic
      subtype or peritoneal carcinosis were excluded. RESULTS: Patients had clinical
      International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n
      = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine
      patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions.
      Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed
      tomography [CT] results)-16 with a PA nodal metastasis measuring more than 5 mm
      and 13 with a nodal metastasis measuring <= 5 mm. Event-free survival rates at 3
      years in patients without PA involvement or with PA metastasis measuring <= or
      more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001).
      CONCLUSION: To our knowledge, this is the largest series of patients reported
      undergoing such a strategy. We obtained the same survival rate for patients with
      PA nodal metastasis <= 5 mm and patients without PA lymph node involvement,
      suggesting that this strategy is highly efficient in such patients. Conversely,
      the survival of patients with PA nodal involvement greater than 5 mm remained
      poor, despite the absence of extrapelvic disease on PET-CT imaging in this
      subgroup.

PMID- 23857968
TI  - Conveying gratitude.

PMID- 23857966
TI  - Phase I pharmacokinetic and pharmacodynamic study of pazopanib in children with
      soft tissue sarcoma and other refractory solid tumors: a children's oncology
      group phase I consortium report.
AB  - PURPOSE: Pazopanib, an oral multikinase angiogenesis inhibitor, prolongs
      progression-free survival in adults with soft tissue sarcoma (STS). A phase I
      pharmacokinetic and pharmacodynamic study of two formulations of pazopanib was
      performed in children with STS or other refractory solid tumors. PATIENTS AND
      METHODS: Pazopanib (tablet formulation) was administered once daily in 28-day
      cycles at four dose levels (275 to 600 mg/m(2)) using the rolling-six design.
      Dose determination for a powder suspension was initiated at 50% of the maximum
      tolerated dose (MTD) for the intact tablet. Ten patients with STS underwent
      dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scanning at
      baseline and 15 +/- 2 days after initiation of pazopanib at the tablet MTD.
      RESULTS: Fifty-three patients were enrolled; 51 were eligible (26 males; median
      age, 12.9 years; range, 3.8 to 23.9 years). Hematologic and nonhematologic
      toxicities were generally mild, with dose-limiting lipase, amylase, and ALT
      elevation, proteinuria, and hypertension. One patient with occult brain
      metastasis had grade 4 intracranial hemorrhage. The MTD was 450 mg/m(2) for
      tablet and 160 mg/m(2) for suspension. Steady-state trough concentrations were
      reached by day 15 and did not seem to be dose dependent. One patient each with
      hepatoblastoma or desmoplastic small round cell tumor achieved a partial
      response; eight patients had stable disease for >= six cycles, seven of whom had
      sarcoma. All patients with evaluable DCE-MRI (n = 8) experienced decreases in
      tumor blood volume and permeability (P < .01). Placental growth factor increased,
      whereas endoglin and soluble vascular endothelial growth factor receptor-2
      decreased (P < .01; n = 41). CONCLUSION: Pazopanib is well tolerated in children,
      with evidence of antiangiogenic effect and potential clinical benefit in
      pediatric sarcoma.

PMID- 23857969
TI  - Prospective study of tailoring whole-body dual-modality [18F]fluorodeoxyglucose
      positron emission tomography/computed tomography with plasma Epstein-Barr virus
      DNA for detecting distant metastasis in endemic nasopharyngeal carcinoma at
      initial staging.
AB  - PURPOSE: To evaluate which patients with nasopharyngeal carcinoma (NPC) obtained
      the greatest benefits from the detection of distant metastasis with
      [(18)F]fluorodeoxyglucose positron emission tomography and computed tomography
      (PET/CT) combined with plasma Epstein-Barr virus (EBV) DNA levels. PATIENTS AND
      METHODS: Consecutive patients with NPC were prospectively enrolled. PET/CT,
      conventional work-up (CWU), and quantification of plasma EBV DNA were performed
      before treatment. The accuracy of these strategies for distant metastases was
      assessed. The costs of the diagnostic strategies were compared. RESULTS: Eighty
      six (14.8%) of the 583 eligible patients were found to have distant metastases;
      71 patients (82.6%) by PET/CT and 31 patients (36.0%) by CWU. In the
      multivariable analysis, advanced N stage (odds ratio, 2.689; 95% CI, 1.894 to
      3.818) and pretreatment EBV DNA level (odds ratio, 3.344; 95% CI, 1.825 to 6.126)
      were significant risk factors for distant metastases. PET/CT was not superior to
      CWU for detecting distant metastases in very low-risk patients (N0-1 with EBV DNA
      < 4,000 copies/mL; P = .062), but was superior for the low-risk patients (N0-1
      with EBV DNA >= 4,000 copies/mL and N2-3 with EBV DNA < 4,000 copies/mL; P =
      .039) and intermediate-risk patients (N2-3 disease with EBV DNA >= 4,000
      copies/mL; P < .001). The corresponding patient management changes based on
      PET/CT were 2.9%, 6.3%, and 16.5%, respectively. The costs per true-positive case
      detected by PET/CT among these groups were Y324,138 (~$47,458), Y96,907
      (~$14,188), and Y34,182 (~$5,005), respectively. CONCLUSION: PET/CT detects more
      distant metastases than conventional staging in patients with NPC. The largest
      benefit in terms of cost and patient management was observed in the subgroup with
      N2-3 disease and EBV DNA >= 4,000 copies/mL.

PMID- 23857970
TI  - Acute lung injury with alveolar hemorrhage as adverse drug reaction related to
      crizotinib.

PMID- 23857971
TI  - Molecular profiling improves classification and prognostication of nodal
      peripheral T-cell lymphomas: results of a phase III diagnostic accuracy study.
AB  - PURPOSE: The differential diagnosis among the commonest peripheral T-cell
      lymphomas (PTCLs; ie, PTCL not otherwise specified [NOS], angioimmunoblastic T
      cell lymphoma [AITL], and anaplastic large-cell lymphoma [ALCL]) is difficult,
      with the morphologic and phenotypic features largely overlapping. We performed a
      phase III diagnostic accuracy study to test the ability of gene expression
      profiles (GEPs; index test) to identify PTCL subtype. METHODS: We studied 244
      PTCLs, including 158 PTCLs NOS, 63 AITLs, and 23 ALK-negative ALCLs. The GEP
      based classification method was established on a support vector machine
      algorithm, and the reference standard was an expert pathologic diagnosis
      according to WHO classification. RESULTS: First, we identified molecular
      signatures (molecular classifier [MC]) discriminating either AITL and ALK
      negative ALCL from PTCL NOS in a training set. Of note, the MC was developed in
      formalin-fixed paraffin-embedded (FFPE) samples and validated in both FFPE and
      frozen tissues. Second, we found that the overall accuracy of the MC was
      remarkable: 98% to 77% for AITL and 98% to 93% for ALK-negative ALCL in test and
      validation sets of patient cases, respectively. Furthermore, we found that the MC
      significantly improved the prognostic stratification of patients with PTCL.
      Particularly, it enhanced the distinction of ALK-negative ALCL from PTCL NOS,
      especially from some CD30+ PTCL NOS with uncertain morphology. Finally, MC
      discriminated some T-follicular helper (Tfh) PTCL NOS from AITL, providing
      further evidence that a group of PTCLs NOS shares a Tfh derivation with but is
      distinct from AITL. CONCLUSION: Our findings support the usage of an MC as
      additional tool in the diagnostic workup of nodal PTCL.

PMID- 23857972
TI  - Phase III trial of sunitinib in combination with capecitabine versus capecitabine
      monotherapy for the treatment of patients with pretreated metastatic breast
      cancer.
AB  - PURPOSE: Metastatic breast cancer (MBC) remains an incurable illness in the
      majority of cases, despite major therapeutic advances. This may be related to the
      ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic
      chemotherapy. Sunitinib, an inhibitor of key molecules involved in
      neoangiogenesis, has an established role in the treatment of metastatic renal
      cell and other cancers and demonstrated activity in a phase II trial in MBC. We
      performed a randomized phase III trial comparing sunitinib plus capecitabine
      (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with
      heavily pretreated MBC. PATIENTS AND METHODS: Eligibility criteria included MBC,
      prior therapy with anthracyclines and taxanes, one or two prior chemotherapy
      regimens for metastatic disease or early relapse after a taxane plus
      anthracycline adjuvant regimen, and adequate organ function and performance
      status. The primary end point was progression-free survival, for which the study
      had 90% power to detect a 50% improvement (from 4 to 6 months). RESULTS: A total
      of 442 patients were randomly assigned. Progression-free survival was not
      significantly different between the treatment arms, with medians of 5.5 months
      (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95%
      CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI,
      0.95 to 1.58; one-sided P = .941). There were no significant differences in
      response rate or overall survival. Toxicity, except for hand-foot syndrome, was
      more severe in the combination arm. CONCLUSION: The addition of sunitinib to
      capecitabine does not improve the clinical outcome of patients with MBC
      pretreated with anthracyclines and taxanes.

PMID- 23857973
TI  - Communication and trust in the care provided to a dying parent: a nationwide
      study of cancer-bereaved youths.
AB  - PURPOSE: To assess children's trust in the care provided to a dying parent during
      the final week of life in relation to end-of-life medical information about
      disease, treatment, and death. METHODS: This nationwide population-based survey
      included 622 (73%) of 851 youths who, 6 to 9 years earlier, at age 13 to 16
      years, lost a parent to cancer. We asked about the children's reception of end-of
      life professional information and trust in the care provided. We also asked about
      depression and several potential risk factors of distrust in the care provided.
      RESULTS: A majority (82%) reported moderate/very much trust in the care provided.
      Compared with children who received end-of-life medical information before their
      loss, the risk of distrust in the care provided was higher in those who received
      no information (risk ratio [RR], 2.5; 95% CI, 1.5 to 4.1), in those who only
      received information afterward (RR, 3.2; 95% CI, 1.7 to 5.9), and in those who
      did not know or remember if end-of-life medical information was provided (RR,
      1.7; 95% CI, 1.1 to 2.5). Those reporting distrust in the care provided had an RR
      of 2.3 (95% CI, 1.5 to 3.5) for depression. Furthermore, the risk of distrust in
      the care provided was higher among children reporting poor efforts to cure (RR,
      5.1; 95% CI, 3.6 to 7.3), and/or a poor relationship with the surviving parent
      (RR, 2.9; 95% CI, 2.0 to 4.1). CONCLUSION: Our study suggests that children's
      trust in the care provided to a dying parent was highest when they received end
      of-life medical information before their loss.

PMID- 23857974
TI  - Long-Term Results of Autologous Hematopoietic Stem-Cell Transplantation After
      High-Dose 90Y-Ibritumomab Tiuxetan for Patients With Poor-Risk Non-Hodgkin
      Lymphoma Not Eligible for High-Dose BEAM.

PMID- 23857975
TI  - High-risk medulloblastoma: a pediatric oncology group randomized trial of
      chemotherapy before or after radiation therapy (POG 9031).
AB  - PURPOSE: To compare event-free survival (EFS) in children with high-risk
      medulloblastoma randomly assigned to receive either chemotherapy before radiation
      or chemotherapy after radiation. PATIENTS AND METHODS: One hundred twelve
      patients were randomly assigned to each arm. Criteria used to categorize patients
      as high risk included M1-4 disease by modified Chang staging classification,
      T3b/T4 disease, or greater than 1.5 cm3 of residual tumor after surgery.
      Postoperatively, children with high-risk medulloblastoma were randomly assigned
      to two arms, either chemotherapy entailing three cycles of cisplatin and
      etoposide before radiation (chemotherapy first [CT1]) or the same chemotherapy
      regimen after radiation (radiation therapy first [RT1]). Both groups received
      consolidation chemotherapy consisting of vincristine and cyclophosphamide.
      RESULTS: The median follow-up time was 6.4 years. Five-year EFS was 66.0% in the
      CT1 arm and 70.0% in the RT1 arm (P = .54), and 5-year overall survival in the
      two groups was 73.1% and 76.1%, respectively (P = .47). In the CT1 arm, 40 of the
      62 patients with residual disease achieved either complete or partial remission.
      CONCLUSION: Five-year EFS did not differ significantly whether, after surgery,
      patients received chemotherapy before or after radiotherapy.

PMID- 23857976
TI  - Translation of central nervous system occupancy from animal models: application
      of pharmacokinetic/pharmacodynamic modeling.
AB  - Translation of central nervous system receptor occupancy from animal models to
      humans has been elusive for many therapeutic targets. However, this may represent
      a valuable link to clinical efficacy for drugs acting within the brain and spinal
      cord. The introduction of positron emission tomography marked a significant
      noninvasive advance in determination of target engagement in the central nervous
      system. Pharmacokinetic/pharmacodynamic (PK/PD) modeling represents a valuable
      tool to translate ex vivo receptor occupancy from relevant animal models to
      humans. Whereas PK properties usually are reasonably scaled across species using
      standard allometric principles, PD properties related to receptor occupancy are
      usually species-independent. The translational value and applicability of PK/PD
      approaches are more directly evident when comparable modeling assumptions and
      mathematical model structures are employed across experiments and analyses. The
      purpose of this article is to review the basic principles of PK/PD analysis of
      receptor occupancy determined using noninvasive positron emission tomography
      imaging and first principles of allometric PK scaling and PD prediction based on
      animal data. By use of the data from the area of pain management, we also provide
      a case study of PK/PD analysis showcasing the importance of PK/PD model
      assumptions in predicting receptor occupancy in humans based on data from animal
      models. 

PMID- 23857977
TI  - Seedless synthesis of layered ZnO nanowall networks on Al substrate for white
      light electroluminescence.
AB  - In this paper, layered ZnO nanowall networks were directly grown on Al substrates
      using a hydrothermal method without predepositing seed layers. The individual ZnO
      nanowalls with a thickness of several nanometers and a size of several hundred
      nanometers were (002) surface dominated, in which the preferential growth
      direction of ZnO was suppressed. White electroluminescence devices were
      fabricated based on Au/polymethylmethacrylate/ZnO-nanowall (metal-insulator
      semiconductor) structures. The chromaticity coordinate of the electroluminescence
      spectrum for the optimal device was calculated as (0.27, 0.34), which is close to
      (0.33, 0.33) of standard white light. 

PMID- 23857979
TI  - The impact of low triiodothyronine levels on mortality is mediated by
      malnutrition and cardiac dysfunction in incident hemodialysis patients.
AB  - OBJECTIVE: Little is known about the impact of low triiodothyronine (T3) levels
      on mortality in end-stage renal disease (ESRD) patients starting hemodialysis
      (HD) and whether this impact is mediated by malnutrition, inflammation, or
      cardiac dysfunction. DESIGN AND METHODS: A prospective cohort of 471 incident HD
      patients from 36 dialysis centers within the Clinical Research Center for ESRD in
      Korea was selected for this study. Based on the median value of T3, patients were
      divided into 'higher' and 'lower' groups, and all-cause and cardiovascular (CV)
      mortality rates were compared. In addition, associations between T3 levels and
      various nutritional, inflammatory, and echocardiographic parameters were
      determined. RESULTS: Compared with those in the 'higher' T3 group, albumin,
      cholesterol, and triglyceride levels, lean body mass estimated by creatinine
      kinetics (LBM-Cr), and normalized protein catabolic rate (nPCR) were
      significantly lower in patients with 'lower' T3 levels. The 'lower' T3 group also
      had a higher left ventricular mass index (LVMI) and a lower ejection fraction
      (EF). Furthermore, correlation analysis revealed significant associations between
      T3 levels and nutritional and echocardiographic parameters. All-cause and CV
      mortality rates were significantly higher in patients with 'lower' T3 levels than
      in the 'higher' T3 group (113.4 vs 18.2 events per 1000 patient-years, P<0.001,
      and 49.8 vs 9.1 events per 1000 patient-years, P=0.001, respectively). The Kaplan
      Meier analysis also showed significantly worse cumulative survival rates in the
      'lower' T3 group (P<0.001). In the Cox regression analysis, low T3 was an
      independent predictor of all-cause mortality even after adjusting for traditional
      risk factors (hazard ratio=3.76, P=0.021). However, the significant impact of low
      T3 on all-cause mortality disappeared when LBM-Cr, nPCR, LVMI, or EF were
      incorporated into the models. CONCLUSION: Low T3 has an impact on all-cause
      mortality in incident HD patients, partly via malnutrition and cardiac
      dysfunction.

PMID- 23857980
TI  - Thermo-optical response of photonic crystal cavities operating in the visible
      spectral range.
AB  - In this paper we study thermo-optical effects in gallium phosphite photonic
      crystal cavities in the visible range. By measuring the shift of narrow
      resonances, we derive the temperature dependency of the local refractive index of
      gallium phosphide in an attoliter volume over a temperature range between 5 and
      300 K at a wavelength of about 605 nm. Additionally, the potential of photonic
      crystal cavities for thermo-optical switching of visible light is investigated.
      As an example we demonstrate thermo-optical switching with 13 dB contrast. 

PMID- 23857978
TI  - Genetics in endocrinology: genetic forms of severe insulin resistance: what
      endocrinologists should know.
AB  - 'Insulin resistance' (IR) is a widely used clinical term. It is usually defined
      as a state characterised by reduced glucose-lowering activity of insulin, but it
      is also sometimes used as a shorthand label for a clinical syndrome encompassing
      major pathologies such as type 2 diabetes, polycystic ovary syndrome, fatty liver
      disease and atherosclerosis. Nevertheless, the precise cellular origins of IR,
      the causal links among these phenomena and the mechanisms underlying them remain
      poorly understood or contentious. Prevalent IR usually results from a genetic
      predisposition interacting with acquired obesity; however, even in some lean
      individuals, very severe degrees of IR can be observed. It is important to
      identify these people as they often harbour identifiable single-gene defects and
      they may benefit from molecular diagnosis, genetic counselling and sometimes
      tailored therapies. Observation of people with known single-gene defects also
      offers the opportunity to make inferences about the mechanistic links between IR
      and common pathologies. Herein, we summarise the currently known monogenic forms
      of severe IR, with an emphasis on the practical aspects of their recognition,
      diagnosis and management. In particular, we draw distinctions among the
      biochemical subphenotypes of IR that arise from primary adipose tissue
      dysfunction or from primary insulin signalling defects and discuss the
      implications of this dichotomy for management. 

PMID- 23857981
TI  - Electrical characteristics of silicon nanowire transistors fabricated by scanning
      probe and electron beam lithographies.
AB  - Silicon nanowire (SiNW) field-effect transistors have been fabricated by
      oxidation scanning probes and electron beam lithographies. The analysis and
      comparison of the electron mobility and subthreshold swing shows that the device
      performance is not affected by the top-down fabrication method. The two methods
      produce silicon nanowire transistors with similar electrical features, although
      oxidation scanning probe lithography generates nanowires with smaller channel
      widths. The values of the electron mobility and the subthreshold swing, 200 cm(2)
      V(-1) s(-1) and 500 mV dec(-1), respectively, are similar to those obtained from
      bottom-up methods. The compatibility of top-down methods with CMOS (complementary
      metal-oxide-semiconductor) procedures, the good electrical properties of the
      nanowire devices and the potential for making sub-10 nanowires, in particular by
      using oxidation scanning probe lithography, make those methods attractive for
      device fabrication. 

PMID- 23857982
TI  - BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival.
AB  - Oxidative stress plays an important role in cancer development and treatment.
      Recent data implicate the tumor suppressor BRCA1 in regulating oxidative stress,
      but the molecular mechanism and the impact in BRCA1-associated tumorigenesis
      remain unclear. Here, we show that BRCA1 regulates Nrf2-dependent antioxidant
      signaling by physically interacting with Nrf2 and promoting its stability and
      activation. BRCA1-deficient mouse primary mammary epithelial cells show low
      expression of Nrf2-regulated antioxidant enzymes and accumulate reactive oxygen
      species (ROS) that impair survival in vivo. Increased Nrf2 activation rescues
      survival and ROS levels in BRCA1-null cells. Interestingly, 53BP1 inactivation,
      which has been shown to alleviate several defects associated with BRCA1 loss,
      rescues survival of BRCA1-null cells without restoring ROS levels. We demonstrate
      that estrogen treatment partially restores Nrf2 levels in the absence of BRCA1.
      Our data suggest that Nrf2-regulated antioxidant response plays a crucial role in
      controlling survival downstream of BRCA1 loss. The ability of estrogen to induce
      Nrf2 posits an involvement of an estrogen-Nrf2 connection in BRCA1 tumor
      suppression. Lastly, BRCA1-mutated tumors retain a defective antioxidant response
      that increases the sensitivity to oxidative stress. In conclusion, the role of
      BRCA1 in regulating Nrf2 activity suggests important implications for both the
      etiology and treatment of BRCA1-related cancers. 

PMID- 23857983
TI  - Immune history shapes specificity of pandemic H1N1 influenza antibody responses.
AB  - Human antibody responses against the 2009 pandemic H1N1 (pH1N1) virus are
      predominantly directed against conserved epitopes in the stalk and receptor
      binding domain of the hemagglutinin (HA) protein. This is in stark contrast to
      pH1N1 antibody responses generated in ferrets, which are focused on the variable
      Sa antigenic site of HA. Here, we show that most humans born between 1983 and
      1996 elicited pH1N1 antibody responses that are directed against an epitope near
      the HA receptor-binding domain. Importantly, most individuals born before 1983 or
      after 1996 did not elicit pH1N1 antibodies to this HA epitope. The HAs of most
      seasonal H1N1 (sH1N1) viruses that circulated between 1983 and 1996 possess a
      critical K133 amino acid in this HA epitope, whereas this amino acid is either
      mutated or deleted in most sH1N1 viruses circulating before 1983 or after 1996.
      We sequentially infected ferrets with a 1991 sH1N1 virus and then a pH1N1 virus.
      Sera isolated from these animals were directed against the HA epitope involving
      amino acid K133. These data suggest that the specificity of pH1N1 antibody
      responses can be shifted to epitopes near the HA receptor-binding domain after
      sequential infections with sH1N1 and pH1N1 viruses that share homology in this
      region. 

PMID- 23857985
TI  - The Vienna declaration on nutrition and non-communicable diseases.

PMID- 23857984
TI  - The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in
      human T cell acute lymphoblastic leukemia.
AB  - The oncogenic transcription factor TAL1/SCL is aberrantly expressed in 60% of
      cases of human T cell acute lymphoblastic leukemia (T-ALL) and initiates T-ALL in
      mouse models. By performing global microRNA (miRNA) expression profiling after
      depletion of TAL1, together with genome-wide analysis of TAL1 occupancy by
      chromatin immunoprecipitation coupled to massively parallel DNA sequencing, we
      identified the miRNA genes directly controlled by TAL1 and its regulatory
      partners HEB, E2A, LMO1/2, GATA3, and RUNX1. The most dynamically regulated miRNA
      was miR-223, which is bound at its promoter and up-regulated by the TAL1 complex.
      miR-223 expression mirrors TAL1 levels during thymic development, with high
      expression in early thymocytes and marked down-regulation after the double
      negative-2 stage of maturation. We demonstrate that aberrant miR-223 up
      regulation by TAL1 is important for optimal growth of TAL1-positive T-ALL cells
      and that sustained expression of miR-223 partially rescues T-ALL cells after TAL1
      knockdown. Overexpression of miR-223 also leads to marked down-regulation of
      FBXW7 protein expression, whereas knockdown of TAL1 leads to up-regulation of
      FBXW7 protein levels, with a marked reduction of its substrates MYC, MYB, NOTCH1,
      and CYCLIN E. We conclude that TAL1-mediated up-regulation of miR-223 promotes
      the malignant phenotype in T-ALL through repression of the FBXW7 tumor
      suppressor. 

PMID- 23857986
TI  - Novel organic LED structures based on a highly conductive polymeric photonic
      crystal electrode.
AB  - In this work we demonstrate the possibility to realize a novel unconventional ITO
      free organic light emitting diode (OLED) utilizing a photonic polymeric
      electrode. Combining electron beam lithography and a plasma etching process to
      partially structure the highly conductive poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) it is possible to
      realize an embedded photonic crystal (PC) structure. The realized PC-anode
      drastically reduces the light trapped in the OLED, demonstrating the possibility
      to eliminate further process stages and making it easier to use this technology
      even on rollable and flexible substrates. 

PMID- 23857987
TI  - Cancer complicating systemic lupus erythematosus--a dichotomy emerging from a
      nested case-control study.
AB  - OBJECTIVES: We determined whether any individual cancers are increased or
      decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE)
      followed for up to 32 years at the University College London Hospitals Lupus
      Clinic, looking for any associated clinical or serological factors and the
      prognosis after cancer diagnosis. METHODS: We undertook a careful retrospective
      review of the medical records and identified all individuals diagnosed with
      cancer. For controls, we selected three other patients in the cohort who had not
      developed cancer, carefully matched for age, sex, ethnicity and disease duration,
      to determine if any obvious differences emerged in a nested case-control design.
      RESULTS: Thirty-three patients developed cancer after being diagnosed with SLE.
      There was a statistically insignificant small increase in overall cancer risk,
      standardized incidence ratios (SIRs) 1.05 (95% CI 0.52-1.58) and increased SIRs
      for cervical, prostate, anal and pancreatic cancers and reduction in breast
      cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin
      and antithyroid globulin antibodies were found to be positively associated with
      cancer risk in multivariate analysis. There was no drug, dose or duration was
      associated with cancer risk. There was a reduction in survival with a cancer
      fatality rate of 84.2% (p < 0.0001). CONCLUSION: We found a very small but
      statistically insignificant increased cancer risk with reduction in survival.
      Whereas some cancers appear to be more common in SLE, notably prostate and
      cervical cancer, others, particularly breast cancer, are less frequent. Multiple
      clinical and serological factors are involved in the increased risk of malignancy
      in SLE. No drug dose or duration effect was identified.

PMID- 23857988
TI  - Association of MeCP2 (rs2075596, rs2239464) genetic polymorphisms with systemic
      lupus erythematosus: a meta-analysis.
AB  - OBJECTIVE: Limited studies have shown an association between the methyl-CpG
      binding protein2 (MeCp2) genetic polymorphisms and systemic lupus erythematosus
      (SLE) in different populations, but the results are inconclusive. In order to get
      a precise and systematic estimation, a meta-analysis was performed. METHODS: A
      systematic literature search using English and Chinese databases (PubMed/Medline,
      Web of Knowledge, Wanfang Data (Chinese), etc.) for the eligible studies was
      performed. Based on heterogeneity among studies, random- or fixed-effects models
      were selected to analyze the risk of SLE associated with single-nucleotide
      polymorphisms (SNPs) of MeCP2 genetic polymorphisms. RESULTS: A significant
      increased risk of both SNPs of MeCP2 genetic variances associated with SLE was
      found. Analysis using a fixed-effects model found an increased risk of SLE with
      the A allele of rs2075596 (OR = 1.41, 95% CI: 1.34 to 1.49, p < 0.001), and the
      random-effects model also identified a risk factor of A allele of rs2239464 (OR =
      1.31, 95% CI: 1.15 to 1.49, p = 0.001). Subgroup analysis and sensitivity
      analysis suggested that the major source of between-study heterogeneity stemmed
      from the difference between diverse ethnic groups. After omitting the smallest
      study, no publication bias was found, which further confirmed the reliability and
      stability of the meta-analysis. CONCLUSIONS: Mutations of SNPs (rs2075596,
      rs2239464) of MeCP2 showed increased risk of developing SLE. Large-scale
      multicenter epidemiological studies in selected populations with other risk
      factors are urgently required.

PMID- 23857990
TI  - Formation of gallium arsenide nanostructures in Pyrex glass.
AB  - In this paper, we report on a simple, low-cost process to grow GaAs
      nanostructures of a few nm diameter and ~50 nm height in Pyrex glass wafers.
      These nanostructures were grown by sequential plasma activation of GaAs and Pyrex
      glass surfaces using a low-temperature hybrid plasma bonding technology in air.
      Raman analyses of the activated surfaces show gallium oxide and arsenic oxide, as
      well as suppressed non-bridging oxygen with aluminate and boroxol chains in
      glass. The flow of alkaline ions toward the cathode and the replacement of
      alkaline ions by Ga and As ions in glass result in the growth of GaAs
      nanostructures in nanopores/nanoscratches in glass. These nanopores/nanoscratches
      are believed to be the origin of the growth of the nanostructures. It was found
      that the length of the GaAs nanostructures may be controlled by an electrostatic
      force. Cross-sectional observation of the bonded interface using high-resolution
      transmission electron microscopy confirms the existence of the nanostructures. A
      possible application of the nanostructures in glass is a filtration system for
      biomolecules. 

PMID- 23857991
TI  - Optically transparent, mechanically durable, nanostructured superhydrophobic
      surfaces enabled by spinodally phase-separated glass thin films.
AB  - We describe the formation and properties of atomically bonded, optical quality,
      nanostructured thin glass film coatings on glass plates, utilizing phase
      separation by spinodal decomposition in a sodium borosilicate glass system.
      Following deposition via magnetron sputtering, thermal processing and
      differential etching, these coatings are structurally superhydrophilic (i.e.,
      display anti-fogging functionality) and demonstrate robust mechanical properties
      and superior abrasion resistance. After appropriate chemical surface
      modification, the surfaces display a stable, non-wetting Cassie-Baxter state and
      exhibit exceptional superhydrophobic performance, with water droplet contact
      angles as large as 172 degrees . As an added benefit, in both superhydrophobic
      and superhydrophilic states these nanostructured surfaces can block ultraviolet
      radiation and can be engineered to be anti-reflective with broadband and
      omnidirectional transparency. Thus, the present approach could be tailored toward
      distinct coatings for numerous markets, such as residential windows, windshields,
      specialty optics, goggles, electronic and photovoltaic cover glasses, and optical
      components used throughout the US military. 

PMID- 23857992
TI  - Indian government approves 50 clinical trials in one day.

PMID- 23857989
TI  - Mestizos with systemic lupus erythematosus develop renal disease early while
      antimalarials retard its appearance: data from a Latin American cohort.
AB  - OBJECTIVES: The objective of this paper is to assess the predictors of time-to
      lupus renal disease in Latin American patients. METHODS: Systemic lupus
      erythematosus (SLE) patients (n = 1480) from Grupo Latino Americano De Estudio de
      Lupus (GLADEL's) longitudinal inception cohort were studied. Endpoint was ACR
      renal criterion development after SLE diagnosis (prevalent cases excluded). Renal
      disease predictors were examined by univariable and multivariable Cox
      proportional hazards regression analyses. Antimalarials were considered time
      dependent in alternative analyses. RESULTS: Of the entire cohort, 265 patients
      (17.9%) developed renal disease after entering the cohort. Of them, 88 (33.2%)
      developed persistent proteinuria, 44 (16.6%) cellular casts and 133 (50.2%) both;
      233 patients (87.9%) were women; mean (+/- SD) age at diagnosis was 28.0 (11.9)
      years; 12.2% were African-Latin Americans, 42.5% Mestizos, and 45.3% Caucasians
      (p = 0.0016). Mestizo ethnicity (HR 1.61, 95% CI 1.19-2.17), hypertension (HR
      3.99, 95% CI 3.02-5.26) and SLEDAI at diagnosis (HR 1.04, 95% CI 1.01-1.06) were
      associated with a shorter time-to-renal disease occurrence; antimalarial use (HR
      0.57, 95% CI 0.43-0.77), older age at onset (HR 0.90, 95% CI 0.85-0.95, for every
      five years) and photosensitivity (HR 0.74, 95% CI 0.56-0.98) were associated with
      a longer time. Alternative model results were consistent with the antimalarial
      protective effect (HR 0.70, 95% CI 0.50-0.99). CONCLUSIONS: Our data strongly
      support the fact that Mestizo patients are at increased risk of developing renal
      disease early while antimalarials seem to delay the appearance of this SLE
      manifestation. These data have important implications for the treatment of these
      patients regardless of their geographic location.

PMID- 23857993
TI  - Quantification of aortic flow by phase-contrast magnetic resonance in patients
      with bicuspid aortic valve.
AB  - AIMS: Bicuspid aortic valve (BAV) causes complex flow patterns in the ascending
      aorta (AAo), which may compromise the accuracy of flow measurement by phase
      contrast magnetic resonance (PC-MR). Therefore, we aimed to assess and compare
      the accuracy of forward flow measurement in the AAo, where complex flow is more
      dominant in BAV patients, with flow quantification in the left ventricular
      outflow tract (LVOT) and the aortic valve orifice (AV), where complex flow is
      less important, in BAV patients and controls. METHODS AND RESULTS: Flow was
      measured by PC-MR in 22 BAV patients and 20 controls at the following positions:
      (i) LVOT, (ii) AV, and (iii) AAo, and compared with the left ventricular stroke
      volume (LVSV). The correlation between the LVSV and the forward flow in the LVOT,
      the AV, and the AAo was good in BAV patients (r = 0.97/0.96/0.93; P < 0.01) and
      controls (r = 0.96/0.93/0.93; P < 0.01). However, in relation with the LVSV, the
      forward flow in the AAo was mildly underestimated in controls and much more in
      BAV patients [median (inter-quartile range): 9% (4%/15%) vs. 22% (8%/30%); P <
      0.01]. This was not the case in the LVOT and the AV. The severity of flow
      underestimation in the AAo was associated with flow eccentricity. CONCLUSION:
      Flow measurement in the AAo leads to an underestimation of the forward flow in
      BAV patients. Measurement in the LVOT or the AV, where complex flow is less
      prominent, is an alternative means for quantifying the systolic forward flow in
      BAV patients.

PMID- 23857994
TI  - Aortic intracardiac echocardiography-guided septal puncture during mitral
      valvuloplasty.
AB  - AIMS: Transoesophageal echocardiography (TEE) and venous intracardiac
      echocardiography (ICE) are traditionally used to visualize the interatrial septum
      (IAS) and the tenting effect of the fossa ovalis in patients undergoing
      percutaneous balloon mitral valvuloplasty (PBMV). The aim of the present study
      was to assess the comparative efficacy and safety of arterial (intra-aortic) ICE
      and venous ICE, compared with TEE (traditional approach), in the patients
      undergoing PBMV. METHODS AND RESULTS: TEE, aortic ICE, and venous ICE were
      consecutively performed in 50 patients (40 +/- 9 years, 86% female). The images
      of intracardiac structures were obtained from both aortic and right atrial loci.
      The IAS was visualized using TEE, aortic ICE, and venous ICE. The mean mitral
      valve area was 1.14 +/- 0.2 cm(2), and the mean left atrial volume index was 57.5
      +/- 12 mL/m(2). The mean size of the visualized septal length was 48 +/- 5 mm by
      TEE, 51 +/- 5 mm by aortic ICE, and 33 +/- 6 mm by venous ICE. The Bland-Altman
      test indicated that the 95% limits of agreement for the measurement of septal
      diameter ranged from -11.0 to +5.9 mm (mean -2.5 mm) between TEE and aortic ICE, 
      2.8 to +33.5 mm (mean +15.3 mm) between TEE and venous ICE, and -36.6 to +0.8 mm
      (mean -17.9 mm) between venous and aortic ICE. Standard venous ICE generally
      tended to yield smaller values compared with TEE and aortic ICE for the
      measurement of septal length. Furthermore, the view of fossa ovalis and 'tenting
      effect' was optimal in 11 patients on venous ICE; however, the fossa ovalis and
      tip of the needle were well visualized in all patients on aortic ICE (P < 0.001).
      There were no major complications with the use of aortic ICE. CONCLUSION: Aortic
      ICE is a superior alternative to venous ICE and facilitates trans-septal puncture
      in patients with mitral stenosis.

PMID- 23857995
TI  - Creation of high density ensembles of nitrogen-vacancy centers in nitrogen-rich
      type Ib nanodiamonds.
AB  - This work explores the possibility of increasing the density of negatively
      charged nitrogen-vacancy centers ([NV(-)]) in nanodiamonds using nitrogen-rich
      type Ib diamond powders as the starting material. The nanodiamonds (10-100 nm in
      diameter) were prepared by ball milling of microdiamonds, in which the density of
      neutral and atomically dispersed nitrogen atoms ([N(0)]) was measured by diffuse
      reflectance infrared Fourier transform spectroscopy. A systematic measurement of
      the fluorescence intensities and lifetimes of the crushed monocrystalline
      diamonds as a function of [N(0)] indicated that [NV(-)] increases nearly linearly
      with [N(0)] at 100-200 ppm. The trend, however, failed to continue for
      nanodiamonds with higher [N(0)] (up to 390 ppm) but poorer crystallinity. We
      attribute the result to a combined effect of fluorescence quenching as well as
      the lower conversion efficiency of vacancies to NV(-) due to the presence of more
      impurities and defects in these as-grown diamond crystallites. The principles and
      practice of fabricating brighter and smaller fluorescent nanodiamonds are
      discussed. 

PMID- 23857996
TI  - Stroke in a young man.

PMID- 23857997
TI  - PPH vs Milligan-Morgan: early and late complications in the treatment of
      haemorrhoidal disease with circumferential prolapse.
AB  - BACKGROUND: The aim of this study was to assess the early and late complications
      of haemorrhoidectomy according to Milligan-Morgan (Milligan-Morgan laser optical
      fibers variant) vs haemorrhoidopexy with PPH-stapler and to assess the long-term
      results in terms of recurrences in circumferential prolapse patients classified
      P4-E4 (PATE 2000). METHODS: Onehundredsixty patients, with haemorrhoidal disease
      classified P4-E4, who underwent surgery between 2001 and 2007, were included in
      an retrospective observational study. Group A (M-M laser fibre) 80 patients (50%)
      (50 Male, 30 Female; median age 39 years, range 23-57 years). Group B (PPH
      Stapler) 80 patients (50%) (58 Male, 22 Female; median age 40 years, range 23-60
      years). RESULT: Early complications were thrombosis (6 cases in M-M vs 1 in PPH)
      and urinary retention (13 M-M vs 5 PPH). There weren't cases of sepsis. Late
      complications have been: occasional bleeding 13.5 % in the M-M-group vs 10 % in
      the PPH-group; defecatory urgency 2.5 % (M-M-group) vs 5% (PPH-group) with p <
      0.1; persistent pain 2.5 % (M-M) vs 5 % (PPH) with p < 0.1; soiling 18.75 % (M-M)
      vs 0 % (PPH) with p < 0.001; recurrences 5 % in PPH-group vs 0 % in M-M (p <
      0.05); residual disease 7.5 % in M-M-group vs 0 % in PPH p < 0.01. CONCLUSIONS:
      PPH-stapler procedure for treatment of haemorrhoidal prolapse is an important
      improvement, but may be followed by severe complications. We think that it has a
      clear indication in the treatment of haemorrhoidary disease with circumferential
      prolapse classified P4-E4.

PMID- 23857998
TI  - Development of a low cost laparostomy technique. Two years experience in the
      Trauma Center of Cesena, Italy.
AB  - BACKGROUND: In the last few years laparostomy has become an even more useful
      option for the surgeon due to the development of the experience in the critical
      abdominal trauma and in the severe surgical urgencies as PANE and peritonitis
      with the introduction of Damage Control as surgical strategy to prevent the
      abdominal compartimental syndrom (ACS). After a laparostomy the surgeon needs to
      provide a delayed fascial closure to achieve the best outcome for the patient.
      The aim of this paper is to illustrate the experience and the results after the
      introduction of a modified laparostomy technique in our surgical activity.
      METHODS: Protection of intestinal content, aspiration under sub-athmospheric
      pressure, control in quality and quantity of the drainage and skin temporary
      closure, rappresent the four principles of the PACS tecnique. In order to
      evaluate the rate of delayed fascial closure and the rate of ACS onset, we have
      retrospectively studied 31 patients over a period of 2 years treated with open
      abdomen with an amount of 36 PACS performed. Routinely IAP measurament was also
      performed. RESULTS: ACS was developed in no patients. IAP was measured on average
      at 19. DFC was achieved in 33 PACS of 36 (91.7%) after 5 days on average (20
      hours as minimum; 20 days as maximum). Aspected mortality (SAPSII) in ICU for
      these patient was 76.5% on average. On 31 patients, 20 (64.5%) died and 11
      (35.5%) survived. CONCLUSION: PACS seems to be an effective, easy and low cost
      technique for the management of open abdomen.

PMID- 23857999
TI  - Ministers are criticised after plans for plain pack cigarettes are put on hold.

PMID- 23858000
TI  - Association of low body temperature and poor outcomes in patients admitted with
      worsening heart failure: a substudy of the Efficacy of Vasopressin Antagonism in
      Heart Failure Outcome Study with Tolvaptan (EVEREST) trial.
AB  - AIMS: Risk stratification in patients admitted with worsening heart failure (HF)
      is essential for tailoring therapy and counselling. Risk models are available but
      rarely used, in part because many require laboratory and imaging results that are
      not routinely available. Body temperature is associated with prognosis in other
      illnesses, and we hypothesized that low body temperature would be associated with
      worse outcomes in patients admitted with worsening HF. METHODS AND RESULTS: The
      Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan
      (EVEREST) trial was an event-driven, randomized, double-blind, placebo-controlled
      study of tolvaptan in 4133 patients hospitalized for worsening HF with an EF
      <40%. Co-primary endpoints were all-cause mortality and cardiovascular (CV) death
      or HF rehospitalization. Body temperature was measured orally at randomization
      and entered in analyses both as a continuous variable and categorized into three
      groups (<36  degrees C, 36-36.5  degrees C, and >36.5  degrees C) using Cox
      regression models. The composite of CV death or HF rehospitalization occurred in
      1544 patients within 1 year. For every 1  degrees C decrease in body temperature,
      the risk of adverse outcomes increased by 16% [hazard raio (HR) 1.16, 95%
      confidence interval (CI) 1.04-1.28], after adjustment for age, gender, race,
      systolic blood pressure, EF, blood urea nitrogen, and serum sodium. In fully
      adjusted analysis, the risk of adverse outcomes in the lowest body temperature
      group (<36  degrees C) was 51% higher than that of the index group (>36.5 
      degrees C) (HR 1.35, 95% CI 1.15-1.58). CONCLUSIONS: Low body temperature is an
      independent marker of poor cardiovascular outcomes in patients admitted with
      worsening HF and reduced EF.

PMID- 23858001
TI  - The G-protein-gated K+ channel, IKACh, is required for regulation of pacemaker
      activity and recovery of resting heart rate after sympathetic stimulation.
AB  - Parasympathetic regulation of sinoatrial node (SAN) pacemaker activity modulates
      multiple ion channels to temper heart rate. The functional role of the G-protein
      activated K(+) current (IKACh) in the control of SAN pacemaking and heart rate is
      not completely understood. We have investigated the functional consequences of
      loss of IKACh in cholinergic regulation of pacemaker activity of SAN cells and in
      heart rate control under physiological situations mimicking the fight or flight
      response. We used knockout mice with loss of function of the Girk4 (Kir3.4) gene
      (Girk4(-/-) mice), which codes for an integral subunit of the cardiac IKACh
      channel. SAN pacemaker cells from Girk4(-/-) mice completely lacked IKACh. Loss
      of IKACh strongly reduced cholinergic regulation of pacemaker activity of SAN
      cells and isolated intact hearts. Telemetric recordings of electrocardiograms of
      freely moving mice showed that heart rate measured over a 24-h recording period
      was moderately increased (10%) in Girk4(-/-) animals. Although the relative
      extent of heart rate regulation of Girk4(-/-) mice was similar to that of wild
      type animals, recovery of resting heart rate after stress, physical exercise, or
      pharmacological beta-adrenergic stimulation of SAN pacemaking was significantly
      delayed in Girk4(-/-) animals. We conclude that IKACh plays a critical role in
      the kinetics of heart rate recovery to resting levels after sympathetic
      stimulation or after direct beta-adrenergic stimulation of pacemaker activity.
      Our study thus uncovers a novel role for IKACh in SAN physiology and heart rate
      regulation. 

PMID- 23858002
TI  - Mechanism of calsequestrin regulation of single cardiac ryanodine receptor in
      normal and pathological conditions.
AB  - Release of Ca(2+) from the sarcoplasmic reticulum (SR) drives contractile
      function of cardiac myocytes. Luminal Ca(2+) regulation of SR Ca(2+) release is
      fundamental not only in physiology but also in physiopathology because abnormal
      luminal Ca(2+) regulation is known to lead to arrhythmias, catecholaminergic
      polymorphic ventricular tachycardia (CPVT), and/or sudden cardiac arrest, as
      inferred from animal model studies. Luminal Ca(2+) regulates ryanodine receptor
      (RyR)2-mediated SR Ca(2+) release through mechanisms localized inside the SR; one
      of these involves luminal Ca(2+) interacting with calsequestrin (CASQ), triadin,
      and/or junctin to regulate RyR2 function. CASQ2-RyR2 regulation was examined at
      the single RyR2 channel level. Single RyR2s were incorporated into planar lipid
      bilayers by the fusion of native SR vesicles isolated from either wild-type (WT),
      CASQ2 knockout (KO), or R33Q-CASQ2 knock-in (KI) mice. KO and KI mice have CPVT
      like phenotypes. We show that CASQ2(WT) action on RyR2 function (either
      activation or inhibition) was strongly influenced by the presence of cytosolic
      MgATP. Function of the reconstituted CASQ2(WT)-RyR2 complex was unaffected by
      changes in luminal free [Ca(2+)] (from 0.1 to 1 mM). The inhibition exerted by
      CASQ2(WT) association with the RyR2 determined a reduction in cytosolic Ca(2+)
      activation sensitivity. RyR2s from KO mice were significantly more sensitive to
      cytosolic Ca(2+) activation and had significantly longer mean open times than
      RyR2s from WT mice. Sensitivity of RyR2s from KI mice was in between that of RyR2
      channels from KO and WT mice. Enhanced cytosolic RyR2 Ca(2+) sensitivity and
      longer RyR2 open times likely explain the CPVT-like phenotype of both KO and KI
      mice. 

PMID- 23858003
TI  - Ca2+ and K+ channels of normal human adrenal zona fasciculata cells: properties
      and modulation by ACTH and AngII.
AB  - In whole cell patch clamp recordings, we found that normal human adrenal zona
      fasciculata (AZF) cells express voltage-gated, rapidly inactivating Ca(2+) and
      K(+) currents and a noninactivating, leak-type K(+) current. Characterization of
      these currents with respect to voltage-dependent gating and kinetic properties,
      pharmacology, and modulation by the peptide hormones adrenocorticotropic hormone
      (ACTH) and AngII, in conjunction with Northern blot analysis, identified these
      channels as Cav3.2 (encoded by CACNA1H), Kv1.4 (KCNA4), and TREK-1 (KCNK2). In
      particular, the low voltage-activated, rapidly inactivating and slowly
      deactivating Ca(2+) current (Cav3.2) was potently blocked by Ni(2+) with an IC50
      of 3 uM. The voltage-gated, rapidly inactivating K(+) current (Kv1.4) was
      robustly expressed in nearly every cell, with a current density of 95.0 +/- 7.2
      pA/pF (n = 64). The noninactivating, outwardly rectifying K(+) current (TREK-1)
      grew to a stable maximum over a period of minutes when recording at a holding
      potential of -80 mV. This noninactivating K(+) current was markedly activated by
      cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate (CDC) and arachidonic acid (AA) and
      inhibited almost completely by forskolin, properties which are specific to TREK-1
      among the K2P family of K(+) channels. The activation of TREK-1 by AA and
      inhibition by forskolin were closely linked to membrane hyperpolarization and
      depolarization, respectively. ACTH and AngII selectively inhibited the
      noninactivating K(+) current in human AZF cells at concentrations that stimulated
      cortisol secretion. Accordingly, mibefradil and CDC at concentrations that,
      respectively, blocked Cav3.2 and activated TREK-1, each inhibited both ACTH- and
      AngII-stimulated cortisol secretion. These results characterize the major Ca(2+)
      and K(+) channels expressed by normal human AZF cells and identify TREK-1 as the
      primary leak-type channel involved in establishing the membrane potential. These
      findings also suggest a model for cortisol secretion in human AZF cells wherein
      ACTH and AngII receptor activation is coupled to membrane depolarization and the
      activation of Cav3.2 channels through inhibition of hTREK-1. 

PMID- 23858004
TI  - What activates inactivation?

PMID- 23858005
TI  - Domain IV voltage-sensor movement is both sufficient and rate limiting for fast
      inactivation in sodium channels.
AB  - Voltage-gated sodium channels are critical for the generation and propagation of
      electrical signals in most excitable cells. Activation of Na(+) channels
      initiates an action potential, and fast inactivation facilitates repolarization
      of the membrane by the outward K(+) current. Fast inactivation is also the main
      determinant of the refractory period between successive electrical impulses.
      Although the voltage sensor of domain IV (DIV) has been implicated in fast
      inactivation, it remains unclear whether the activation of DIV alone is
      sufficient for fast inactivation to occur. Here, we functionally neutralize each
      specific voltage sensor by mutating several critical arginines in the S4 segment
      to glutamines. We assess the individual role of each voltage-sensing domain in
      the voltage dependence and kinetics of fast inactivation upon its specific
      inhibition. We show that movement of the DIV voltage sensor is the rate-limiting
      step for both development and recovery from fast inactivation. Our data suggest
      that activation of the DIV voltage sensor alone is sufficient for fast
      inactivation to occur, and that activation of DIV before channel opening is the
      molecular mechanism for closed-state inactivation. We propose a kinetic model of
      sodium channel gating that can account for our major findings over a wide voltage
      range by postulating that DIV movement is both necessary and sufficient for fast
      inactivation. 

PMID- 23858006
TI  - ATP release and Ca2+ signalling by human bronchial epithelial cells following
      Alternaria aeroallergen exposure.
AB  - Exposure of human bronchial epithelial (HBE) cells from normal and asthmatic
      subjects to extracts from Alternaria alternata evoked a rapid and sustained
      release of ATP with greater efficacy observed in epithelial cells from asthmatic
      patients. Previously, Alternaria allergens were shown to produce a sustained
      increase in intracellular Ca2+ concentration ([Ca2+]i) that was dependent on the
      coordinated activation of specific purinergic receptor (P2Y2 and P2X7) subtypes.
      In the present study, pretreatment with a cell-permeable Ca2+-chelating compound
      (BAPTA-AM) significantly inhibited ATP release, indicating dependency on [Ca2+]i.
      Alternaria-evoked ATP release exhibited a greater peak response and a slightly
      lower EC50 value in cells obtained from asthmatic donors compared to normal
      control cells. Furthermore, the maximum increase in [Ca2+]i resulting from
      Alternaria treatment was greater in cells from asthmatic patients compared to
      normal subjects. The vesicle transport inhibitor brefeldin A and BAPTA-AM
      significantly blocked Alternaria-stimulated incorporation of fluorescent lipid
      (FM1-43)-labelled vesicles into the plasma membrane and ATP release. In addition,
      inhibiting uptake of ATP into exocytotic vesicles with bafilomycin also reduced
      ATP release comparable to the effects of brefeldin A and BAPTA-AM. These results
      indicate that an important mechanism for Alternaria-induced ATP release is Ca2+
      dependent and involves exocytosis of ATP. Serine and cysteine protease inhibitors
      also reduced Alternaria-induced ATP release; however, the sustained increase in
      [Ca2+]i typically observed following Alternaria exposure appeared to be
      independent of protease-activated receptor (PAR2) stimulation.

PMID- 23858007
TI  - Brief history of arrhythmia in the WPW syndrome - the contribution of George
      Ralph Mines.
AB  - George Ralph Mines studied the basic principles of reentry and published his data
      in The Journal of Physiology in 1913. Exactly 100 years later we discuss his
      first electrophysiological experiments and how his results lead to the insight
      that was the basis for the treatment of the clinical arrhythmias seen in Wolff
      Parkinson-White syndrome.

PMID- 23858008
TI  - Microcircuit mechanisms involved in paired associative stimulation-induced
      depression of corticospinal excitability.
AB  - Synaptic weight changes induced by temporal correlations between the spikes of
      pre- and postsynaptic neurons are referred to as spike-timing-dependent
      plasticity (STDP). Transcranial magnetic stimulation (TMS) induces long-lasting
      effects on corticospinal excitability, if it is repetitively paired with
      stimulation of afferents from a corresponding contralateral hand region at short
      intervals (paired associative stimulation, PAS). PAS-induced plasticity has been
      linked with synaptic STDP. We aimed to investigate which elements of the cortical
      microcircuitry sustain and govern PAS-induced depression of corticospinal
      excitability in the target muscle representation (and enhancement of excitability
      in its functional surround). We show that the time window during which the
      interaction between both stimulus-induced cortical events leads to immediate post
      interventional depression is short (<4.5 ms). The depressant PAS effects at the
      target representation were completely blocked by applying a subthreshold magnetic
      pulse 3 ms before the principal TMS pulse, even when the strength of the latter
      was adjusted to generate a motor-evoked potential of similar amplitude to that
      with the unconditioned magnetic pulse. Epidural recordings from the cervical cord
      of a patient showed that under this condition late TMS-evoked I-waves remain
      suppressed. When the intensity of the TMS component during PAS was lowered -
      sufficient to allow activation of inhibitory neurons, but insufficient to
      activate corticospinal neurons - excitability of short-latency intracortical
      inhibition remained unchanged. PAS-induced facilitation in the functional
      surround followed the same pattern as the centre-depressant effects. These
      findings may suggest that excitability-depressant PAS-induced effects are due to
      weakening of excitatory synapses between upper cortical layer principal neurons,
      but not those located on the corticospinal neuron, or inhibitory synapses.
      Inhibitory interneurons involved in short-latency intracortical inhibition are
      gate-keepers to producing centre-depressant/surround-facilitatory PAS effects.
      Based on these and earlier findings we propose a model specifying the composition
      and laminar location of the involved microcircuit of PAS-induced plasticity that
      may enhance its utility as a model of STDP in humans.

PMID- 23858009
TI  - Acute inhibition of diacylglycerol lipase blocks endocannabinoid-mediated
      retrograde signalling: evidence for on-demand biosynthesis of 2
      arachidonoylglycerol.
AB  - The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) produced by
      diacylglycerol lipase alpha (DGLalpha) is one of the best-characterized
      retrograde messengers at central synapses. It has been thought that 2-AG is
      produced 'on demand' upon activation of postsynaptic neurons. However, recent
      studies propose that 2-AG is pre-synthesized by DGLalpha and stored in neurons,
      and that 2-AG is released from such 'pre-formed pools' without the participation
      of DGLalpha. To address whether the 2-AG source for retrograde signalling is the
      on-demand biosynthesis by DGLalpha or the mobilization from pre-formed pools, we
      examined the effects of acute pharmacological inhibition of DGL by a novel potent
      DGL inhibitor, OMDM-188, on retrograde eCB signalling triggered by Ca(2+)
      elevation, Gq/11 protein-coupled receptor activation or synergy of these two
      stimuli in postsynaptic neurons. We found that pretreatment for 1 h with OMDM-188
      effectively blocked depolarization-induced suppression of inhibition (DSI), a
      purely Ca(2+)-dependent form of eCB signalling, in slices from the hippocampus,
      striatum and cerebellum. We also found that at parallel fibre-Purkinje cell
      synapses in the cerebellum OMDM-188 abolished synaptically induced retrograde eCB
      signalling, which is known to be caused by the synergy of postsynaptic Ca(2+)
      elevation and group I metabotropic glutamate receptor (I-mGluR) activation.
      Moreover, brief OMDM-188 treatments for several minutes were sufficient to
      suppress both DSI and the I-mGluR-induced retrograde eCB signalling in cultured
      hippocampal neurons. These results are consistent with the hypothesis that 2-AG
      for synaptic retrograde signalling is supplied as a result of on-demand
      biosynthesis by DGLalpha rather than mobilization from presumptive pre-formed
      pools.

PMID- 23858010
TI  - Laryngeal and tracheal afferent nerve stimulation evokes swallowing in
      anaesthetized guinea pigs.
AB  - We describe swallowing reflexes evoked by laryngeal and tracheal vagal afferent
      nerve stimulation in anaesthetized guinea pigs. The swallowing reflexes evoked by
      laryngeal citric acid challenges were abolished by recurrent laryngeal nerve
      (RLN) transection and mimicked by electrical stimulation of the central cut ends
      of an RLN. By contrast, the number of swallows evoked by upper airway/pharyngeal
      distensions was not significantly reduced by RLN transection but they were
      virtually abolished by superior laryngeal nerve transection. Laryngeal citric
      acid-evoked swallowing was mimicked by laryngeal capsaicin challenges,
      implicating transient receptor potential vanilloid 1 (TRPV1)-expressing laryngeal
      afferent nerves arising from the jugular ganglia. The swallowing evoked by citric
      acid and capsaicin and evoked by electrical stimulation of either the tracheal or
      the laryngeal mucosa occurred at stimulation intensities that were typically
      subthreshold for evoking cough in these animals. Swallowing evoked by airway
      afferent nerve stimulation also desensitized at a much slower rate than cough. We
      speculate that swallowing is an essential component of airway protection from
      aspiration associated with laryngeal and tracheal afferent nerve activation.

PMID- 23858011
TI  - Smooth muscle cell transient receptor potential polycystin-2 (TRPP2) channels
      contribute to the myogenic response in cerebral arteries.
AB  - Intravascular pressure-induced vasoconstriction is a smooth muscle cell-specific
      mechanism that controls systemic blood pressure and organ regional blood flow.
      Smooth muscle cell polycystin-1 and -2 (TRPP1 and -2) proteins modulate the
      myogenic response in mesenteric arteries, but involvement in other vascular beds
      is unclear. Here, we examined TRPP2 expression, cellular distribution, cation
      currents (ICat), and physiological functions in smooth muscle cells of rat and
      human cerebral arteries. We demonstrate that TRPP2 is the major TRPP isoform
      expressed in cerebral artery smooth muscle cells, with message levels higher than
      those of TRPP1. Arterial biotinylation and immunofluorescence indicated that
      TRPP2 is located primarily (~88%) in the smooth muscle cell plasma membrane. RNA
      interference reduced TRPP2 expression by ~55% compared to control, but did not
      alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage
      dependent Ca(2+) (CaV1.2) channels, other ion channel proteins that modulate
      myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)(-1))
      bath solution stimulated Gd(3+)-sensitive ICat in smooth muscle cells that were
      reduced by selective TRPP2 knockdown. TRPP2 knockdown did not alter myogenic tone
      at 20 mmHg but reduced tone between ~28 and 39% over an intravascular pressure
      range between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter
      depolarization-induced (60 mmol l K(+)) vasoconstriction. In summary, we show
      that TRPP2 is expressed in smooth muscle cells of resistance-size cerebral
      arteries, resides primarily in the plasma membrane, and contributes to the
      myogenic response. Data also suggest that TRPP2 differentially regulates the
      myogenic response in cerebral and mesenteric arteries.

PMID- 23858013
TI  - The surgical treatment of paraesophageal hernias.
AB  - Paraesophageal hernias account for about 5 to 10% of all hiatal hernias. The
      surgical approach to these hernias has radically changed over the last 15 years,
      as mostly patients who are symptomatic are operated on nowadays, and preferably
      by a laparoscopic approach rather than by laparotomy or thoracotomy. We reviewed
      the surgical repair of paraesophageal hernias, focusing particularly on the
      operative approach and technique.

PMID- 23858012
TI  - Ca2+ and cAMP cross-talk in mitochondria.
AB  - While mitochondrial Ca(2+) homeostasis has been studied for several decades and
      many of the functional roles of Ca(2+) accumulation within the matrix have been
      at least partially clarified, the possibility of modulation of the organelle
      functions by cAMP remains largely unknown. In this contribution we briefly
      summarize the key aspects of Ca(2+) and cAMP signalling pathways in mitochondria.
      In particular, we focus on recent findings concerning the discovery of an
      autonomous cAMP toolkit within the mitochondrial matrix, its crossroad with
      mitochondrial Ca(2+) signalling and its role in controlling ATP synthesis. The
      discovery of a cAMP signalling, and the demonstration of a cross-talk between
      cAMP and Ca(2+) inside mitochondria, open the way to a re-evaluation of these
      organelles as integrators of multiple second messengers. A description of the
      main methods presently available to measure Ca(2+) and cAMP in mitochondria of
      living cells with genetically encoded probes is also presented. 

PMID- 23858014
TI  - GSK executives admit to bribery and tax crimes, China claims.

PMID- 23858016
TI  - Trade agreement could lock NHS into competitive market, campaign groups say.

PMID- 23858015
TI  - Too much of a good thing? When to stop catch-up vaccination.
AB  - During the 20th century, deaths from a range of serious infectious diseases
      decreased dramatically due to the development of safe and effective vaccines.
      However, infant immunization coverage has increased only marginally since the
      1960s, and many people remain susceptible to vaccine-preventable diseases. "Catch
      up vaccination" for age groups beyond infancy can be an attractive and effective
      means of immunizing people who were missed earlier. However, as newborn
      vaccination rates increase, catch-up vaccination becomes less attractive: the
      number of susceptible people decreases, so the cost to find and vaccinate each
      unvaccinated person may increase; in addition, the number of infected individuals
      decreases, so each unvaccinated person faces a lower risk of infection. This
      article presents a general framework for determining the optimal time to
      discontinue a catch-up vaccination program. We use a cost-effectiveness
      framework: we consider the cost per quality-adjusted life year gained of catch-up
      vaccination efforts as a function of newborn immunization rates over time and
      consequent disease prevalence and incidence. We illustrate our results with the
      example of hepatitis B catch-up vaccination in China. We contrast results from a
      dynamic modeling approach with an approach that ignores the impact of vaccination
      on future disease incidence. The latter approach is likely to be simpler for
      decision makers to understand and implement because of lower data requirements.

PMID- 23858017
TI  - Cortical lesion load correlates with diffuse injury of multiple sclerosis normal
      appearing white matter.
AB  - BACKGROUND: Degeneration of central nervous system normal appearing white matter
      (NAWM) underlies disability and progression in multiple sclerosis (MS). Axon loss
      typifies NAWM degeneration. OBJECTIVE: The objective of this paper is to assess
      correlation between cortical lesion load and magnetisation transfer ratio (MTR)
      of the NAWM in MS. This was in order to test the hypothesis that cortical lesions
      cause NAWM degeneration. METHODS: Nineteen patients with MS underwent 7 Tesla
      magnetisation-prepared-rapid-acquisition-gradient-echo (MPRAGE), and
      magnetisation transfer ratio (MTR) brain magnetic resonance imaging (MRI).
      Cortical lesions were identified using MPRAGE and MTR images of cortical ribbons.
      White matter lesions (WMLs) were segmented using MPRAGE images. WML maps were
      subtracted from white matter volumes to produce NAWM masks. Pearson correlation
      was calculated for NAWM MTR vs cortical lesion load, and WML volumes. RESULTS:
      Cortical lesion volumes and counts all had significant correlation with NAWM mean
      MTR. The strongest correlation was with cortical lesion volumes obtained using
      MTR images (r = -0.6874, p = 0.0006). WML volume had no significant correlation
      with NAWM mean MTR (r = -0.08706, p = 0.3615). CONCLUSION: Our findings are
      consistent with the hypothesis that cortical lesions cause NAWM degeneration.
      This implicates cortical lesions in the pathogenesis of NAWM axon loss, which
      underpins long-term disability and progression in MS.

PMID- 23858018
TI  - Limits on working time reduce interns' surgery experience, study shows.

PMID- 23858019
TI  - A simple and reproducible surgical technique for the management of preauricular
      sinuses.
AB  - Preauricular sinus is a relatively common congenital anomaly that mainly exists
      on the anterior aspect of the anterior limb of the ascending helix. Although many
      surgical techniques have been developed, extirpation of the sinus is not easy
      because of the ramifications of the sinus, remnants of the sinus wall, and
      infection with or without formation of abscesses, which can all lead to disease
      recurrence. In our institution, we have surgically treated a total of 141 cases
      of congenital preauricular sinuses. Instead of using the conventional lacrimal
      probe and methylene blue method, we used a gentian violet-soaked Cottonoid, which
      has antibacterial effects against the main pathogen responsible for causing
      infection of the preauricular sinus. Results have been very favorable, with a
      zero recurrence rate. We present here a simple and reproducible surgical
      technique using a gentian violet-soaked Cottonoid that even beginning surgeons
      can easily follow. 

PMID- 23858020
TI  - A new mechanism for inappropriate therapy observed during recommended device
      software upgrade of a St Jude Medical Fortify STTM implantable cardioverter
      defibrillator.

PMID- 23858021
TI  - Breast cancer and pacemakers.
AB  - AIMS: The combination of breast cancer and the need for a pacemaker is
      infrequent, and device implantation under these circumstances may be a technical
      challenge with several treatment options, most of them complex. METHODS AND
      RESULTS: Eight patients, all women, with an average age of 69.62 +/- 11.4 years.
      We present a technique for patients with bilateral breast cancer who need a
      pacemaker or those who had already implanted a device and developed a homolateral
      breast cancer. All the pacemakers were implanted in a neck pocket, as a first
      implantation or if they were moved from a prepectoral pocket to the neck. Seven
      patients had a good outcome and one had an infection. CONCLUSION: We suggest a
      simple alternative to lead extraction or epicardial approach in patients with
      coexisting breast cancer and the need for a rhythm control device consisting in
      placing the device in a neck pocket and preserving the existing leads by
      tunnelling them either above or below the clavicle.

PMID- 23858022
TI  - Urgent catheter ablation for sustained ventricular tachyarrhythmias in patients
      with acute heart failure decompensation.
AB  - AIMS: Ventricular tachycardia (VT) and ventricular fibrillation (VF) are not
      uncommon in patients hospitalized with acute heart failure (AHF). We sought to
      evaluate the efficacy of urgent radiofrequency catheter ablation (RFCA) for
      recurrent VT/VF during AHF decompensations. METHODS AND RESULTS: The present
      study retrospectively analysed the data of 15 consecutive patients (69 +/- 9
      years, ischaemic heart disease in 10), who underwent urgent RFCA for frequent
      drug-refractory VT/VF episodes during an AHF decompensation with pulmonary
      congestion. The target arrhythmias were clinically documented monomorphic VTs in
      10 patients, frequent premature ventricular contractions (PVCs) triggering VF in
      4, and both in 1. The mean left ventricular ejection fraction was 26 +/- 8%. The
      maximum number of arrhythmia episodes over 24 h was 9.1 +/- 11.7. All RFCA
      sessions were completed without any major complications except for a temporary
      deterioration of pulmonary congestion in three patients (20%). Elimination and
      non-inducibility of the target arrhythmias were achieved in 13 patients (87%).
      Successful ablation site electrograms showed Purkinje potentials for all 5 PVCs
      triggering VF and 4 of 14 clinically documented monomorphic VTs (29%). Five
      patients (33%) underwent second sessions 10 +/- 4 days after the first session
      for acute recurrences. Sustained VT/VF was completely suppressed during admission
      in 12 patients (80%), and the AHF ameliorated in 13 patients (93%). Twelve
      patients (80%) were discharged alive. CONCLUSION: Urgent RFCA for drug-resistant
      sustained ventricular tachyarrhythmias during AHF decompensations would be an
      appropriate therapeutic option. Purkinje fibres can be ablation targets not only
      in those with PVCs triggering VF, but also in those with monomorphic VT.

PMID- 23858023
TI  - Inappropriate use of antiarrhythmic drugs in paroxysmal and persistent atrial
      fibrillation in a large contemporary international survey: insights from
      RealiseAF.
AB  - AIMS: International atrial fibrillation (AF) guidelines have defined optimal
      drugs for patients with various underlying diseases, but the extent to which real
      life practice complies with these guidelines is unknown. This study aimed to
      evaluate the appropriate use of antiarrhythmic drugs (AADs) in patients with
      paroxysmal and persistent AF from the RealiseAF survey, according to the 2006
      American College of Cardiology/American Heart Association/European Society of
      Cardiology AF guidelines. METHODS AND RESULTS: RealiseAF was an international
      cross-sectional, observational survey of 10 523 eligible patients from 26
      countries on 4 continents, with >=1 AF episode documented by standard
      electrocardiogram or by Holter monitoring in the last 12 months. Participating
      physicians were randomly selected during 2009-10 from lists of office-based or
      hospital-based cardiologists and internists. Overall, 4947 patients with
      paroxysmal (n = 2606) or persistent AF (n = 2341) were included; mean (standard
      deviation) age was 64.7 (12.4) and 66.0 (11.8) years, respectively. Class Ic
      drugs were prescribed in 589 patients (11.9%); however, in 20.0% of these
      patients, the indication was not consistent with published guidelines. Similarly,
      for the 219 patients prescribed sotalol (4.4%), 16.0% received treatment for an
      indication that deviated from the published guidelines. Amiodarone was prescribed
      as first-line therapy in 1268 patients (25.6%), but 49.9% of these did not have
      heart failure or hypertension with significant left ventricular hypertrophy.
      CONCLUSION: The use of AADs for persistent or paroxysmal AF in this large
      contemporary international survey showed some deviations from international
      guidelines. The highest discordance came with the use of amiodarone in first
      line. Clearly, there is a large discrepancy between published guidelines and
      current practice.

PMID- 23858024
TI  - Screening of genes encoding junctional candidates in arrhythmogenic right
      ventricular cardiomyopathy/dysplasia.
AB  - AIMS: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an
      inherited cardiomyopathy characterized by fibro-fatty replacement of the right
      ventricle and ventricular arrhythmias. The major disease-causing genes encode
      cardiac desmosomal components but are involved in only ~50% of patients. To
      identify the missing genetic determinants, we used a candidate gene approach,
      focusing on the 3'-untranslated region (UTR) of the main ARVC/D gene PKP2 and on
      additional genes involved in desmosomal structure or function. METHODS AND
      RESULTS: We screened a population of 64 ARVC/D probands with no identified
      mutations in any of the five known desmosomal genes (PKP2, DSG2, DSP, DSC2, and
      JUP). No putative mutation was identified in the 3'-UTR of PKP2 or in PNN,
      CTNNA3, CAV1, or PLN coding sequences. In a single proband, we identified two
      rare heterozygous missense variants affecting evolutionary conserved residues:
      c.175G>A (p.Gly59Arg) in PERP and c.1811A>G (p.Asp604Gly) in PKP4 (minor allele
      frequency <0.5% in control population). CONCLUSION: Our study suggests that
      mutations in the candidate genes studied and regulation of PKP2 mRNA via 3'-UTR
      dependent mechanisms are unlikely to be major causes of ARVC/D in the studied
      population. Additional studies are needed to investigate the putative effects of
      rare PKP4 and PERP variants in this disease.

PMID- 23858025
TI  - Chronic venous disease: Correlation between ultrasound findings and the clinical,
      etiologic, anatomic and pathophysiologic classification.
AB  - OBJECTIVE: The aim of the study was to investigate association between clinical
      manifestation of chronic venous disease and the presence and severity of
      functional venous disease. METHOD: A cross-sectional study was conducted in 14
      towns in Serbia. All men and women aged >18 years, consecutively coming to venous
      specialists (47 specialists) were included in the study. Patients who were
      previously treated for chronic venous disease were excluded. Patients were
      classified according to the clinical category of clinical, etiologic, anatomic
      and pathophysiologic classification for chronic venous disease. Reflux and/or
      obstruction were determined by using a color duplex ultrasound. RESULTS: The
      study included 1679 chronic venous disease patients. Color duplex ultrasound was
      performed in 1029 (61.3%) of them who formed the final study group. Reflux was
      found in 76.8% of patients - 53.1% had reflux in superficial, 7.2% in deep and
      16.1% in perforator veins. Obstruction was found in 31.9% of patients -
      superficial in 14.8% of patients and deep in 16.9%. Deep obstruction was even
      found in clinical, etiologic, anatomic and pathophysiologic C0s-C1 categories.
      Reflux and obstruction combined were revealed in 19.1% of patients. Reflux in
      deep and perforator veins and reflux and obstruction combined were significantly
      associated with clinical, etiologic, anatomic and pathophysiologic clinical
      categories being the most frequent in patients with venous ulcers. CONCLUSION:
      Clinical, etiologic, anatomic and pathophysiologic clinical categories of chronic
      venous disease are strongly correlated with functional disease especially with
      reflux in deep and perforator veins, and reflux and obstruction combined. The
      presence of deep obstruction in patients with chronic venous disease belonging to
      clinical, etiologic, anatomic and pathophysiologic C0s-C1 category could justify
      recommendation for color duplex ultrasonography in all patients with symptoms of
      chronic venous disease but without clear clinical signs.

PMID- 23858026
TI  - Cilostazol strengthens the endothelial barrier of postcapillary venules from the
      rat mesentery in situ.
AB  - OBJECTIVE: Although cilostazol, a phosphodiesterase 3 inhibitor, has been
      suggested to strengthen the endothelial barrier using cultured endothelial
      monolayers, its effect has not been tested in vivo. We, therefore, investigated
      effects of cilostazol on barrier properties of postcapillary venules of the rat
      in situ. METHODS: Cilostazol was administered to the rats through oral gavage at
      4 hours before the measurements. The hydraulic permeability (L(p)) and the
      effective osmotic pressure (sigmaDeltapi), molecular sieving properties of
      microvascular walls, were estimated in single mesenteric postcapillary venules by
      a micro-occlusion technique, first during control perfusion and then in the
      presence of histamine. RESULTS: When the vessels were inflamed with histamine,
      cilostazol attenuated a transient increase in L(p) and prevented sigmaDeltapi
      from falling. Furthermore, it reduced baseline L(p) under a control state.
      CONCLUSION: Cilostazol appears to tighten the endothelial barrier in situ, at
      least in part by inhibiting the cAMP-degrading enzyme in the endothelium.

PMID- 23858027
TI  - Assessing public health intervention practices in a Danish municipality: applying
      criteria based on the European Community Health Promotion Indicator Development
      (EUHPID) model.
AB  - AIM: To develop a set of assessment criteria and assess public health
      interventions at municipal level in Denmark using the European Community Health
      Promotion Indicator Development (EUHPID) model to support more effective planning
      and funding allocation in public health. METHODS: Based on knowledge synthesis, a
      set of assessment criteria were developed to classify interventions into the four
      types of public health provided by the EUHPID model: health promotion, health
      protection, disease prevention, and health care. Information was then collected
      on all current public health interventions in Varde Municipality within a 3-month
      period in spring 2009. Finally, the interventions were categorised using the
      developed assessment criteria. RESULTS: The knowledge synthesis process resulted
      in the development of a set of assessment criteria and the 154 reported public
      health interventions were divided into relevant types using these criteria. 57%
      of the interventions were based on a salutogenic health promotion approach, 33%
      on a pathogenic disease prevention approach, 10% on the pathogenic health
      protection approach, and 0% on the pathogenic health care approach. CONCLUSIONS:
      The assessment criteria based on the EUHPID model can be useful and have wider
      global significance for planning public health interventions, allocating
      appropriate funding to support public health interventions, and thereby
      encouraging and supporting more effective intersectoral working practices.

PMID- 23858028
TI  - CCL19 and CCL28 augment mucosal and systemic immune responses to HIV-1 gp140 by
      mobilizing responsive immunocytes into secondary lymph nodes and mucosal tissue.
AB  - Induction of broad and potent neutralizing Abs at the mucosal portals of entry
      remains a primary goal for most vaccines against mucosally acquired viral
      infections. Selection of appropriate adjuvants capable of promoting both systemic
      and mucosal responses will be crucial for the development of effective
      immunization strategies. In this study, we investigated whether plasmid
      codelivery of cytokines APRIL, CCL19, or CCL28 can enhance Ag-induced immune
      responses to HIV-1 gp140. Our results demonstrated that pCCL19 and pCCL28, but
      not pAPRIL, significantly enhanced Ag-specific systemic and mucosal Ab responses.
      gp140-specific Abs in serum enhanced by pCCL19 or pCCL28 were broadly distributed
      across all four IgG subclasses, of which IgG1 was predominant. The enhanced
      systemic and mucosal Abs showed increased neutralizing activity against both
      homologous and heterologous HIV-1, and potency correlated with gp140-specific
      serum IgG and vaginal IgA levels. Measurement of gp140-specific cytokines
      produced by splenocytes demonstrated that pCCL19 and pCCL28 augmented balanced
      Th1/Th2 responses. pCCL19 and pCCL28 also increased IgA(+) cells in colorectal
      mucosal tissue. pCCL19 codelivery resulted in an increase of CCR7(+) CD11c(+)
      cells in mesenteric lymph nodes and both CCR7(+) CD11c(+) cells and CCR7(+)
      CD3e(+) cells in spleen, whereas pCCL28 codelivery resulted in an augment of
      CCR10(+) CD19(+) cells in both spleen and mesenteric lymph nodes. Together, our
      data indicate that pCCL19 and pCCL28 can enhance HIV-1 envelope-specific systemic
      and mucosal Ab responses, as well as T cell responses. Such enhancements appear
      to be associated with mobilization of responsive immunocytes into secondary
      lymphoid organs and mucosal tissues through interactions with corresponding
      receptors.

PMID- 23858030
TI  - Serum amyloid A3 binds MD-2 to activate p38 and NF-kappaB pathways in a MyD88
      dependent manner.
AB  - Serum amyloid A (SAA) 3 is a major component of the acute phase of inflammation.
      We previously reported that SAA3 served as an endogenous peptide ligand for TLR4
      to facilitate lung metastasis. Because these experiments were performed with SAA3
      recombinant proteins purified from Escherichia coli or mammalian cells, we could
      not rule out the possibility of LPS contamination. In this study, we used SAA3
      synthetic peptides to eliminate the presence of LPS in SAA3. We found that the
      SAA3 synthetic peptide (aa 20-86) (20-86) stimulated cell migration and activated
      p38 in a manner dependent on TLR4, MD-2, and MyD88. SAA3 (20-86) also activated
      NF-kappaB and Rho small GTPase. Using surface plasmon resonance analysis, the
      binding constant KD values between SAA3 (20-86) or SAA3 (43-57) and TLR4/MD-2
      protein highly purified by the baculovirus system were 2.2 and 30 MUM,
      respectively. FLAG-tagged SAA3 tightly bound to protein A-tagged MD-2, but not to
      TLR4 in baculovirus coinfection experiments. Although SAA3 (20-86) caused a low,
      but appreciable level of endocytosis in TLR4, it induced the upregulation of both
      IL-6 and TNF-alpha, but not IFN-beta1. An i.v. injection of SAA3 (43-57) induced
      the lung recruitment of CD11b(+)Gr-1(+) cells at an estimated serum concentration
      around its KD value toward TLR4/MD-2. Taken together, these results suggest that
      SAA3 directly binds MD-2 and activates the MyD88-dependent TLR4/MD-2 pathway.

PMID- 23858029
TI  - Inhibition of CD8+ T cell-derived CD40 signals is necessary but not sufficient
      for Foxp3+ induced regulatory T cell generation in vivo.
AB  - Current models of CD4(+) T cell help suggest a major role for CD154 binding to
      CD40 expressed on dendritic cells, with a lesser role for direct T:T interactions
      via CD40 expressed on CD8(+) T cells. However, the contribution of CD8(+) T cell
      derived CD40 signals during the donor-reactive T cell response to a transplant
      has never been studied. In this study, we examined the graft-rejection kinetics
      and CD4(+) and CD8(+) donor-reactive T cell responses under conditions in which
      CD40 was genetically ablated only on APC, as well as under conditions in which
      CD40 was genetically ablated only on donor-reactive CD8(+) T cells. Our results
      revealed a significant role for CD8(+) T cell-expressed CD40 in the augmentation
      of donor-reactive CD8(+) T cell responses following transplantation and showed
      that CD40 expressed on CD8(+) T cells must be inhibited to allow conversion of
      CD4(+) T cells into induced regulatory T cells. Thus, this study identifies a
      major role for CD8(+) T cell-derived CD40 signals as a critical switch factor
      that both promotes optimal differentiation of cytokine-producing CD8(+) effector
      T cell responses and inhibits the differentiation of Ag-specific Foxp3(+) induced
      regulatory T cells in vivo.

PMID- 23858031
TI  - IL-17RA is essential for optimal localization of follicular Th cells in the
      germinal center light zone to promote autoantibody-producing B cells.
AB  - Germinal centers (GCs) provide a microenvironment that promotes and regulates the
      interactions of B cells with follicular Th (TFH) cells. In this study, we show
      that there are significantly higher frequencies of CXCR5(+)ICOS(+) TFH cells in
      autoimmune BXD2 mice, and these cells express both IL-21R and IL-17RA. Although
      IL-17 and IL-21 are both important for the formation of spontaneous GCs and
      development of pathogenic autoantibodies, IL-21, but not IL-17, is required for
      the proper development of TFH cells in BXD2 mice. The total numbers of TFH cells
      and their ability to induce B cell responses in vitro were not affected by a
      deficiency of IL-17RA in BXD2-Il17ra(-/-) mice, the majority of CXCR5(+) TFH
      cells from BXD2-Il17ra(-/-) mice were, however, not localized in the GC light
      zone (LZ). Interruption of IL-17 signaling, either acutely by AdIL-17R:Fc or
      chronically by Il17ra(-/-), disrupted TFH-B interactions and abrogated the
      generation of autoantibody-forming B cells in BXD2 mice. IL-17 upregulated the
      expression of regulator of G-protein signaling 16 (RGS16) to promote the ability
      of TFH to form conjugates with B cells, which was abolished in TFH cells from
      BXD2-Rgs16(-/-) mice. The results suggests that IL-17 is an extrinsic stop signal
      that it acts on postdifferentiated IL-17RA(+) TFH to enable its interaction with
      responder B cells in the LZ niche. These data suggest a novel concept that TFH
      differentiation and its stabilization in the LZ are two separate checkpoints and
      that IL-21 and IL-17 act at each checkpoint to enable pathogenic GC development. 

PMID- 23858032
TI  - Multiplex and genome-wide analyses reveal distinctive properties of KIR+ and
      CD56+ T cells in human blood.
AB  - Killer cell Ig-like receptors (KIRs) on NK cells have been linked to a wide
      spectrum of health conditions such as chronic infections, autoimmune diseases,
      pregnancy complications, cancers, and transplant failures. A small subset of
      effector memory T cells also expresses KIRs. In this study, we use modern
      analytic tools including genome-wide and multiplex molecular, phenotypic, and
      functional assays to characterize the KIR(+) T cells in human blood. We find that
      KIR(+) T cells primarily reside in the CD56(+) T population that is distinctively
      DNAM-1(high) with a genome-wide quiescent transcriptome, short telomere, and
      limited TCR excision circles. During CMV reactivation in bone marrow transplant
      recipients, KIR(+)CD56(+) T cells rapidly expanded in real-time but not
      KIR(+)CD56(-) T cells or KIR(+) NK cells. In CMV(+) asymptomatic donors, as much
      as 50% of CD56(+) T cells are KIR(+), and most are distinguishably
      KIR2DL2/3(+)NKG2C(+)CD57(+). Functionally, the KIR(+)CD56(+) T cell subset lyses
      cancer cells and CMVpp65-pulsed target cells in a dual KIR-dependent and TCR
      dependent manner. Analysis of metabolic transcriptome confirms the immunological
      memory status of KIR(+)CD56(+) T cells in contrast to KIR(-)CD56(+) T cells that
      are more active in energy metabolism and effector differentiation. KIR(-)CD56(+)
      T cells have >25-fold higher level of expression of RORC than the KIR(+)
      counterpart and are a previously unknown producer of IL-13 rather than IL-17 in
      multiplex cytokine arrays. Our data provide fundamental insights into KIR(+) T
      cells biologically and clinically. 

PMID- 23858033
TI  - Increased numbers of monocyte-derived dendritic cells during successful tumor
      immunotherapy with immune-activating agents.
AB  - Local treatment with selected TLR ligands or bacteria such as bacillus Calmette
      Guerin increases antitumor immune responses and delays tumor growth. It is
      thought that these treatments may act by activating tumor-associated dendritic
      cells (DCs), thereby supporting the induction of antitumor immune responses.
      However, common parameters of successful immune activation have not been
      identified. We used mouse models to compare treatments with different immune
      activating agents for the ability to delay tumor growth, improve priming of tumor
      specific T cells, and induce early cytokine production and DC activation.
      Treatment with polyinosinic-polycytidylic acid or a combination of monosodium
      urate crystals and Mycobacterium smegmatis was effective at delaying the growth
      of s.c. B16 melanomas, orthotopic 4T1 mammary carcinomas, and reducing 4T1 lung
      metastases. In contrast, LPS, monosodium urate crystals, or M. smegmatis alone
      had no activity. Effective treatments required both NK1.1(+) and CD8(+) cells,
      and resulted in increased T cell priming and the infiltration of NK cells and
      CD8(+) T cells in tumors. Unexpectedly, both effective and ineffective treatments
      increased DC numbers and the expression of costimulatory molecules in the tumor
      draining lymph node. However, only effective treatments induced the rapid
      appearance of a population of monocyte-derived DCs in the draining lymph node,
      early release of IL-12p70 and IFN-gamma, and low IL-10 in the serum. These
      results suggest that the activation of existing DC subsets is not sufficient for
      the induction of antitumor immune responses, whereas early induction of Th1
      cytokines and monocyte-derived DCs are features of successful activation of
      antitumor immunity. 

PMID- 23858034
TI  - B cell-specific deficiencies in mTOR limit humoral immune responses.
AB  - Generation of high-affinity Abs in response to Ags/infectious agents is essential
      for developing long-lasting immune responses. B cell maturation and Ab responses
      to Ag stimulation require Ig somatic hypermutation (SHM) and class-switch
      recombination (CSR) for high-affinity responses. Upon immunization with either
      the model Ag 4-hydroxy-3-nitrophenylacetyl hapten (NP) conjugated to chicken
      gamma globulin lysine (NP-CGG) or heat-killed Streptococcus pneumoniae capsular
      type 14 protein (Pn14), knock-in (KI) mice hypomorphic for mTOR function had a
      decreased ability to form germinal centers, develop high-affinity anti-NP
      specific or anti-Pn14-specific Abs, and perform SHM/CSR. Hypomorphic mTOR mice
      also had a high mortality (40%) compared with wild-type (WT) (0%) littermates and
      had lower pneumococcal surface protein A-specific Ab titers when immunized and
      challenged with live S. pneumoniae infection. Mice with mTOR deleted in their B
      cell lineage (knockout [KO]) also produced fewer splenic germinal centers and
      decreased high-affinity Ab responses to NP-CGG than did their WT littermates. CSR
      rates were lower in mTOR KI and KO mice, and pharmacologic inhibition of mTOR in
      WT B cells resulted in decreased rates of ex vivo CSR. RNA and protein levels of
      activation-induced cytidine deaminase (AID), a protein essential for SHM and CSR,
      were lower in B cells from both KI and B cell-specific KO mice, concomitant with
      increases in phosphorylated AKT and FOXO1. Rescue experiments increasing AID
      expression in KI B cells restored CSR levels to those in WT B cells. Thus, mTOR
      plays an important immunoregulatory role in the germinal center, at least
      partially through AID signaling, in generating high-affinity Abs. 

PMID- 23858035
TI  - microRNA-17-92 regulates IL-10 production by regulatory T cells and control of
      experimental autoimmune encephalomyelitis.
AB  - microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little
      is known about the functional relevance of individual miRNA loci. We identified
      the miR-17-92 cluster as CD28 costimulation dependent, suggesting that it may be
      key for Treg development and function. Although overall immune homeostasis was
      maintained in mice with miR-17-92-deficient Tregs, expression of the miR-17-92
      miRNA cluster was critical for Treg accumulation and function during an acute
      organ-specific autoimmune disease in vivo. Treg-specific loss of miR-17-92
      expression resulted in exacerbated experimental autoimmune encephalitis and
      failure to establish clinical remission. Using peptide-MHC tetramers, we
      demonstrate that the miR-17-92 cluster was specifically required for the
      accumulation of activated Ag-specific Treg and for differentiation into IL-10
      producing effector Treg. 

PMID- 23858036
TI  - Human CD1a deficiency is common and genetically regulated.
AB  - CD1 proteins evolved to present diverse lipid Ags to T cells. In comparison with
      MHC proteins, CD1 proteins exhibit minimal allelic diversity as a result of
      nonsynonymous single nucleotide polymorphisms (SNPs). However, it is unknown if
      common SNPs in gene regulatory regions affect CD1 expression and function. We
      report surprising diversity in patterns of inducible CD1a expression on human
      dendritic cells (DCs), spanning the full range from undetectable to high density,
      a finding not seen with other CD1 isoforms. CD1a-deficient DCs failed to present
      mycobacterial lipopeptide to T cells but had no defects in endocytosis, cytokine
      secretion, or expression of costimulatory molecules after LPS treatment. We
      identified an SNP in the 5' untranslated region (rs366316) that was common and
      strongly associated with low CD1a surface expression and mRNA levels (p = 0.03
      and p = 0.001, respectively). Using a CD1a promoter-luciferase system in
      combination with mutagenesis studies, we found that the polymorphic allele
      reduced luciferase expression by 44% compared with the wild-type variant (p <
      0.001). Genetic regulation of lipid Ag presentation by varying expression on
      human DCs provides a mechanism for achieving population level differences in
      immune responses despite limited structural variation in CD1a proteins. 

PMID- 23858037
TI  - The efficacy and safety of FSK0808, filgrastim biosimilar: a multicenter, non
      randomized study in Japanese patients with breast cancer.
AB  - OBJECTIVE: FSK0808 is a filgrastim biosimilar. This study assessed the efficacy
      and safety of FSK0808 in patients with breast cancer. METHODS: One hundred and
      four breast cancer patients undergoing chemotherapy were enrolled in the study.
      FSK0808 was used to treat the neutropenia experienced by the patients in the
      course of their chemotherapy. Efficacy was evaluated by the recovery of absolute
      neutrophil count following FSK0808 administration based on the duration of
      neutropenia in patients who received pre- or postoperative chemotherapy
      containing fluorouracil, epirubicin and cyclophosphamide. Adverse events were
      evaluated in accordance with the Common Terminology Criteria for Adverse Events
      version 3.0. The incidence of febrile neutropenia and generation of an anti
      granulocyte colony-stimulating factor antibody were also evaluated. RESULTS: The
      average duration of neutropenia in Cycle 2 was 2.2 days with a standard deviation
      of 1.5 days. The upper limit of the 97.5% one-sided confidence interval was 2.5
      days and was confirmed not to exceed 3.0 days, which was defined as the threshold
      value of absolute neutrophil count recovery. The incidence of febrile neutropenia
      across all treatment cycles was 34.6%. Observed adverse drug reactions with an
      incidence of > 5% were back pain (60.6%), bone pain (9.6%), alanine
      aminotransferase increase (8.7%), aspartate aminotransferase increase (5.8%) and
      arthralgia (5.8%). Production of the anti-granulocyte colony-stimulating factor
      antibody was not observed in any patient during the study. CONCLUSIONS: FSK0808
      was safe and well tolerated in breast cancer patients undergoing chemotherapy and
      effectively stimulated neutrophil recovery.

PMID- 23858038
TI  - Adverse reactions related to treatment compliance during BCG maintenance therapy
      for non-muscle-invasive bladder cancer.
AB  - OBJECTIVE: The aim of the study was to investigate the factor of adverse
      reactions related to compliance with Mycobacterium bovis bacillus Calmette-Guerin
      maintenance therapy in patients with high-risk non-muscle-invasive bladder
      cancer. METHODS: This study was a post hoc analysis using the database of a
      randomized controlled trial that examined the efficacy of bacillus Calmette
      Guerin (Connaught strain) maintenance therapy. Among the 42 patients assigned to
      the bacillus Calmette-Guerin maintenance therapy group, six patients dropped out
      or withdrew consent before the bacillus Calmette-Guerin maintenance therapy. The
      adverse reactions and clinical backgrounds of the remaining 36 patients who
      underwent bacillus Calmette-Guerin maintenance therapy were compared between the
      two groups: the patients who completed the bacillus Calmette-Guerin maintenance
      therapy (the Completed group), and those who discontinued the bacillus Calmette
      Guerin maintenance therapy (the Discontinued group). RESULTS: Of the 36 patients
      who underwent bacillus Calmette-Guerin maintenance therapy, 15 (41.7%) were in
      the Completed group and 21 (58.3%) were in the Discontinued group. Local adverse
      reactions (>=G2) were observed during maintenance therapy in 86.7% of the
      Completed group and 95.2% of the Discontinued group. As for adverse reactions
      during the induction therapy (bacillus Calmette-Guerin induction therapy), the
      frequencies of gross hematuria and systemic adverse reactions (any grade) tended
      to be higher in the Discontinued group than in the Completed group, although not
      significantly so. In the Cochran-Armitage trend test, the linear T trend (i.e.
      the trend in the risk of an increased rate of discontinuation according to gross
      hematuria and systemic adverse reactions with bacillus Calmette-Guerin induction
      therapy) was statistically significant (P = 0.0179). CONCLUSIONS: Most patients
      who completed bacillus Calmette-Guerin maintenance therapy experienced local
      adverse reactions (>=G2) during the maintenance therapy. Gross hematuria and
      systemic adverse reactions during bacillus Calmette-Guerin induction therapy
      might be related to the discontinuation of bacillus Calmette-Guerin maintenance
      therapy because of severe adverse reactions.

PMID- 23858039
TI  - Systematic evaluation of prophylactic neck dissection for the treatment of
      papillary thyroid carcinoma.
AB  - OBJECTIVE: The objective of the study was to evaluate the efficacy of
      prophylactic neck dissection in the treatment of papillary thyroid cancer and to
      provide guidelines for clinical practice. METHOD: Relevant clinical trials on
      prophylactic neck dissection in the treatment of papillary thyroid cancer were
      retrieved using PubMed, MEDLINE, EMBASE and Cochrane Controlled Trials Register
      until August 2012. Information was extracted according to the Cochrane systematic
      review methods. RevMan 5.0 was used for meta-analysis. RESULTS: Nine controlled
      clinical trials were included in this meta-analysis. Compared with patients who
      underwent thyroidectomy alone (control group), patients who underwent
      thyroidectomy plus prophylactic neck dissection (experimental group) showed a
      higher incidence of transient hypocalcemia (P = 0.02), but no significant changes
      were observed in the incidence of neck lymph node recurrence (P = 0.69), central
      neck lymph node recurrence (P = 0.61), lateral neck lymph node recurrence (P =
      0.70), permanent hypocalcemia (P = 0.44), transient vocal cord paralysis (P =
      0.13), permanent vocal cord paralysis (P = 0.26) and hematoma incidence (P =
      0.39). CONCLUSIONS: Combined thyroidectomy and prophylactic neck dissection may
      be effective in the treatment of patients with papillary thyroid cancer, without
      more complications compared with thyroidectomy alone.

PMID- 23858040
TI  - Pore directions for the expression of a Ca2+-activated chloride channel.

PMID- 23858041
TI  - p53: the tumour suppressor turns mitochondrial regulator.

PMID- 23858042
TI  - Responses of glomus cells to hypoxia and acidosis.

PMID- 23858043
TI  - Reply from Y. Lu, C. A. Whiteis, K. A. Sluka, M. W. Chapleau and F. M. Abboud.

PMID- 23858044
TI  - HMGB1 levels are increased in patients with juvenile idiopathic arthritis,
      correlate with early onset of disease, and are independent of disease duration.
AB  - OBJECTIVE: High mobility group box chromosomal protein 1 (HMGB1) has been
      implicated as a mediator of inflammation in rheumatoid arthritis (RA), while its
      role in juvenile idiopathic arthritis (JIA) has not been described. To evaluate
      the role of HMGB1 in the inflammatory process in JIA and its potential as a
      therapeutic target, we investigated whether extracellular HMGB1 is detectable in
      JIA and if so, to correlate the levels with established inflammatory markers and
      clinical measures. METHODS: Matching samples of blood and synovial fluid (SF)
      were collected from 23 patients with JIA. Levels of HMGB1, soluble receptor for
      advanced glycation endproducts, S100A12, myeloid-related protein 8/14, and other
      inflammatory mediators were analyzed. RESULTS: Significantly increased HMGB1
      levels were recorded in SF compared to blood samples from patients with JIA. The
      amount of HMGB1 was highest in patients with early disease onset irrespective of
      disease duration. In contrast, the proinflammatory S100 protein and interleukin 8
      were highest in patients in early phases of disease. Matrix metalloproteinase-3,
      a marker of cartilage destruction, was higher in patients with late disease
      onset, indicating similarities with RA in that patient subgroup. CONCLUSION:
      Levels of extracellular HMGB1 are increased in the inflamed joints of patients
      with JIA. This warrants further studies of HMGB1 as a mediator of JIA
      pathogenesis as well as a biomarker for inflammatory activity and as a target for
      therapy. The variation in levels of HMGB1 and S100 proteins in relation to
      disease onset indicates a difference in inflammatory phenotype during disease
      progression.

PMID- 23858045
TI  - The 15% rule in scleroderma: the frequency of severe organ complications in
      systemic sclerosis. A systematic review.
AB  - OBJECTIVE: The prevalence of organ complications in scleroderma (systemic
      sclerosis; SSc) varies by definition used. This study was done to determine the
      frequency of several features of SSc. METHODS: A search of Medline-Ovid/Embase,
      PubMed, and Scopus databases from 1980 to November 30, 2011, was conducted to
      identify relevant articles with at least 50 patients with SSc extracting
      prevalence of each organ complication. Study quality was assessed using the
      STROBE (Strengthening The Reporting of OBservational studies in Epidemiology)
      checklist. Pooled prevalence was calculated using the random effects method.
      Heterogeneity was quantified using I(2). RESULTS: A total of 5916 articles were
      identified (913 from Medline-Ovid/Embase, 1009 from PubMed, and 3994 from
      Scopus); 5665 were excluded, leaving 251 articles for full-text review, with 69
      included. Where available, frequencies were also included from the Canadian
      Scleroderma Research Group. Many severe complications in SSc occur about 15% of
      the time, including cardiac involvement (15%, 95% CI 6-24), diastolic dysfunction
      (16%, 95% CI 14-17), estimated pulmonary artery pressure > 40 mm Hg (18%, 95% CI
      14-21), pulmonary arterial hypertension by right heart catheterization (15%, 95%
      CI 12-17), forced vital capacity (FVC) < 70% predicted (15%, 95% CI 12-17), FVC <
      80% predicted (17%, 95% CI 12-21), myositis (13%, 95% CI 10-17), inflammatory
      arthritis (12%, 95% CI 9-16), Sjogren overlap (13%, 95% CI 10-16), and digital
      ulcers (DU; 15%, 95% CI 10-20); and 15% of DU have complications (amputations
      12%, 95% CI 8-16, and hospitalizations 13%, 95% CI 6-21). Scleroderma renal
      crisis is uncommon but occurs in almost 15% (12%, 95% CI 5-19) of cases of
      disseminated cutaneous SSc. There is no 15% rule within skin and gastrointestinal
      tract for SSc. CONCLUSION: The "15%" rule for frequency of significant organ
      involvement in SSc is helpful.

PMID- 23858046
TI  - Relationship between hip dysplasia, pain, and osteoarthritis in a cohort of
      patients with hip symptoms.
AB  - OBJECTIVE: The relationship between acetabular dysplasia (HD) and hip
      osteoarthritis (OA) remains unclear, especially for mild forms of dysplasia. Our
      objectives were to estimate the prevalence of HD in a population-based sample
      with symptoms and to evaluate potential associations linking HD, hip OA, and hip
      pain. METHODS: Individuals 40 to 75 years of age with symptoms in 1 or both hips
      were recruited during a multiregional prevalence survey. All study participants
      underwent examination and radiographs. Radiographs were evaluated using Kellgren
      Lawrence staging (with stages >= 2 indicating hip OA) and HD measures [center
      edge (CE) angle, acetabular inclination angle (HTE), acetabular depth (AD), and
      vertical center-anterior margin angle]. RESULTS: We studied both hips of 842
      individuals (1684 hips), among whom 203 had hip OA. Compared to left hips, right
      hips had significantly smaller CE angles and significantly greater AD and HTE
      values (p <= 0.001). Overall, the prevalence of HD ranged from 7.6% to 22.2% of
      the hips depending on the measure used. The prevalence of HD was higher in
      individuals with hip OA, with significant differences for abnormal HTE (19.1% vs
      11.4%; p < 0.0001) and abnormal CE (11.3% vs 7.5%; p = 0.04). By logistic
      regression, only abnormal HTE remained associated with OA. Same-side hip pain was
      not statistically more common in individuals with HD after stratification on OA
      status (p = 0.12). CONCLUSION: Our study confirms the relationship between OA and
      HD, particularly as defined based on the HTE angle.

PMID- 23858047
TI  - Single-nucleotide polymorphism and haplotypes of TNIP1 associated with systemic
      lupus erythematosus in a Chinese Han population.
AB  - OBJECTIVE: To determine the association of systemic lupus erythematosus (SLE)
      with single-nucleotide polymorphisms (SNP) in the TNIP1 gene and compare the
      expression of this gene in cases and controls from a Chinese Han population in
      this replication study. METHODS: Matrix-assisted laser desorption ionization time
      of-flight mass spectrometry was used to genotype 19 SNP in TNIP1 in Chinese Han
      patients with SLE (n = 341) and controls (n = 356). Genotypes were analyzed by
      codominant, dominant, and recessive models. Analysis of allele frequencies and
      linkage disequilibrium was also performed. Western blotting and qRT-PCR were used
      to measure the expression of these genes in peripheral blood mononuclear cells of
      SLE cases and controls. RESULTS: Seven SNP loci were significantly associated
      with SLE in our population (p < 0.05 for all comparisons). Two TNIP1 gene
      haplotypes (ATTGCGC and GTCCTAT) were associated with SLE (p = 0.0246 and p =
      0.0024, respectively). Western blotting and qRT-PCR results provide evidence that
      patients with SLE had significantly reduced expression of TNIP1/ABIN-1 relative
      to controls. CONCLUSION: Analysis of SNP in the TNIP1 gene and expression of this
      gene in peripheral blood lymphocytes indicated these SNP were associated with the
      occurrence of SLE in Han Chinese patients. Future studies should examine the
      roles of these SNP in the pathogenesis of SLE.

PMID- 23858048
TI  - Expression of methotrexate transporters and metabolizing enzymes in rheumatoid
      synovial tissue.
AB  - OBJECTIVE: To determine whether methotrexate (MTX) affects the expression of
      genes involved in the transport [SLC19A1 (RFC1), ABCB1 (MDR1), ABCC1 (multidrug
      resistance proteins 1), ABCG2 (BCRP)], metabolism [gamma-glutamyl hydrolase
      (GGH), folylpolyglutamate synthetase (FPGS)], and mechanism of action of MTX
      [thymidylate synthase, MTR, MTRR] in rheumatoid synovium. METHODS: Synovial
      tissue samples were obtained from 20 patients with rheumatoid arthritis (RA).
      Gene expression was undertaken using quantitative real-time PCR. RESULTS: All the
      genes examined were expressed in all samples. Expression of SLC19A1, GGH, FPGS,
      ABCC1, and MTRR was significantly higher in patients receiving MTX compared to
      those not receiving MTX (p < 0.05). The ratio of FPGS:GGH gene expression was 2.7
      +/- 0.51 ng/ml GAPDH (range 0.67-9.58). CONCLUSION: Genes involved in the
      transport, metabolism, and mechanism of action of MTX are expressed in rheumatoid
      joint synovium. These data provide evidence that MTX has the potential to be
      polyglutamated within the joint. The higher expression of FPGS compared to GGH in
      synovial tissue might favor production of long-chain MTX polyglutamates. Thus MTX
      has the potential to exert its therapeutic effects at the primary site of the
      inflammatory process in RA.

PMID- 23858050
TI  - Temporal dynamics of recovery from extinction shortly after extinction
      acquisition.
AB  - Evidence suggests that extinction is new learning. Memory acquisition involves
      both short-term memory (STM) and long-term memory (LTM) components; however, few
      studies have examined early phases of extinction retention. Retention of auditory
      fear extinction was examined at various time points. Shortly (1-4 h) after
      extinction acquisition spontaneous recovery was high compared to that after
      longer delays (8-24 h). Recall of a consolidated extinction trace was also
      impaired if it was preceded 1 h by extinction of a novel CS; propranolol did not
      attenuate this effect. These results suggest poor extinction retention reflects a
      retrieval impairment caused by the aversive experience of extinction training. 

PMID- 23858049
TI  - Effect of enthesitis on 1505 Brazilian patients with spondyloarthritis.
AB  - OBJECTIVE: To analyze the clinical effect of enthesitis in a large Brazilian
      cohort of patients with spondyloarthritis (SpA). METHODS: A common protocol of
      investigation was prospectively applied to 1505 patients with SpA in 29 centers
      in Brazil. Clinical and demographic variables and disease indexes were
      investigated. The Maastricht Ankylosing Spondylitis Enthesitis Score was used to
      investigate the enthesitis component. Ankylosing spondylitis was the most
      frequent disease in the group (65.4%). Others were psoriatic arthritis (18.4%),
      undifferentiated SpA (6.7%), reactive arthritis (3.3%), and enteropathic
      arthritis (3.2%). RESULTS: At least 1 affected enthesis was observed in 54% of
      the patients with SpA, with a mean of 2.12 +/- 2.98 entheses affected. According
      to the clinical presentation, enthesitis was significantly more frequent in
      patients with axial + peripheral joint involvement compared to isolated axial or
      peripheral involvement (p < 0.001). There was a statistical association between
      the presence of enthesites and axial symptoms (buttock pain, cervical pain, and
      hip pain), and peripheral symptoms (lower limb arthritis, number of painful and
      swollen joints; p < 0.05). Patients with enthesitis also presented higher mean
      scores of Bath Ankylosing Spondylitis Functional Index (BASFI; p < 0.001), Bath
      Ankylosing Spondylitis Disease Activity Index (p < 0.001), and Ankylosing
      Spondylitis Quality of Life (ASQoL; p < 0.001). Multivariate logistic regression
      showed that BASFI (p < 0.0001; OR 74.839), ASQoL (p = 0.0001; OR 14.645), and
      Achilles tendonitis (p = 0.0059; OR 7.593) were associated with work incapacity.
      CONCLUSION: The clinical presence of enthesitis in this large cohort of patients
      with SpA was frequent and was associated with a significant increase in disease
      activity and decline in functional capacity and quality of life.

PMID- 23858051
TI  - Steroid hormone (20-hydroxyecdysone) modulates the acquisition of aversive
      olfactory memories in pollen forager honeybees.
AB  - Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on
      associative olfactory learning in the honeybee, Apis mellifera. 20-E impaired the
      bees' ability to associate odors with punishment during aversive conditioning,
      but did not interfere with their ability to associate odors with a food reward
      (appetitive learning). The steroid had a significant impact also on the
      expression of amine-receptor genes in centers of the brain involved in the
      formation and recall of associative olfactory memories (mushroom bodies). 20-E
      increased expression of the dopamine receptor gene, Amdop2, and reduced the
      expression of the putative dopamine/ecdysone receptor gene, Amgpcr19.
      Interestingly, Amgpcr19 tended to be highly expressed in the brains of foragers
      that exhibited strong aversive learning, but expressed at lower levels in bees
      that performed well in appetitive learning assays. In 2-d-old bees, transcript
      levels of the same gene could be reduced by queen mandibular pheromone, a
      pheromone that blocks aversive learning in young worker bees. As ecdysteroid
      levels rise to a peak ~2 d after adult emergence and then fall to low levels in
      foragers, we examined aversive learning also in young worker bees. Aversive
      learning performance in 2-d-old bees was consistently poor. The results of this
      study indicate that learning in honeybees can be modulated by ecdysteroids. They
      highlight, in addition, a potential involvement of the putative dopamine/ecdysone
      receptor, AmGPCR19, in hormonal regulation of associative olfactory learning in
      the honeybee. 

PMID- 23858052
TI  - The protective effects of caffeic acid phenethyl ester against toluene-induced
      nephrotoxicity in rats.
AB  - Caffeic acid phenethyl ester (CAPE) has antioxidant and anti-inflammatory
      properties. The aim of this study is to examine the negative effects of toluene
      on kidney tissues and functions and to investigate the protective effects of CAPE
      against toluene-induced nephrotoxicity in rats. A total of 21 male Wistar rats
      were divided into three groups of equal number in each. The rats in group I were
      the controls. Toluene was intraperitoneally injected into the rats in group II
      with a dose of 500 mg/kg. Rats in group III received CAPE daily while exposed to
      toluene. After 14 days of experimental period, all rats were killed by
      decapitation. Enzymatic activities of superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px), and catalase (CAT) and malondialdehyde (MDA) levels were
      studied in the rat kidneys. Blood urea nitrogen (BUN) and serum creatinine levels
      were measured for renal function. The CAT and SOD enzyme activities and serum
      creatinine levels were significantly increased in rats treated with toluene when
      compared with the controls. But GSH-Px activity, MDA, and BUN levels showed
      statistically nonsignificant changes. However, increased CAT and SOD enzyme
      activities and decreased serum creatinine levels were detected in the rats that
      received CAPE while exposed to toluene. The GSH-Px activity and MDA and BUN
      levels in the same group did not show statistically significant changes. The
      results of our study demonstrated that toluene damages kidney tissue and is a
      nephrotoxic substance. CAPE was able to prevent the renal damage as antioxidant,
      antitoxic, and nephroprotective agent. 

PMID- 23858053
TI  - Letter from the editor.

PMID- 23858054
TI  - Experimental validation of displacement underestimation in ARFI ultrasound.
AB  - Acoustic radiation force impulse (ARFI) imaging is an elastography technique that
      uses ultrasonic pulses to displace and track tissue motion. Previous modeling
      studies have shown that ARFI displacements are susceptible to underestimation due
      to lateral and elevational shearing that occurs within the tracking resolution
      cell. In this study, optical tracking was utilized to experimentally measure the
      displacement underestimation achieved by acoustic tracking using a clinical
      ultrasound system. Three optically translucent phantoms of varying stiffness were
      created, embedded with subwavelength diameter microspheres, and ARFI excitation
      pulses with F/1.5 or F/3 lateral focal configurations were transmitted from a
      standard linear array to induce phantom motion. Displacements were tracked using
      confocal optical and acoustic methods. As predicted by earlier finite element
      method studies, significant acoustic displacement underestimation was observed
      for both excitation focal configurations; the maximum underestimation error was
      35% of the optically measured displacement for the F/1.5 excitation pulse in the
      softest phantom. Using higher F/#, less tightly focused beams in the lateral
      dimension improved accuracy of displacements by approximately 10 percentage
      points. This work experimentally demonstrates limitations of ARFI implemented on
      a clinical scanner using a standard linear array and sets up a framework for
      future displacement tracking validation studies. 

PMID- 23858056
TI  - Abstracts of the 38th International Symposium on Ultrasonic Imaging and Tissue
      Characterization. June 10-12, 2013, Arlington, VA.

PMID- 23858055
TI  - Task-oriented comparison of power spectral density estimation methods for
      quantifying acoustic attenuation in diagnostic ultrasound using a reference
      phantom method.
AB  - Reported here is a phantom-based comparison of methods for determining the power
      spectral density (PSD) of ultrasound backscattered signals. Those power spectral
      density values are then used to estimate parameters describing alpha(f), the
      frequency dependence of the acoustic attenuation coefficient. Phantoms were
      scanned with a clinical system equipped with a research interface to obtain
      radiofrequency echo data. Attenuation, modeled as a power law alpha(f)= alpha0 f
      (beta), was estimated using a reference phantom method. The power spectral
      density was estimated using the short-time Fourier transform (STFT), Welch's
      periodogram, and Thomson's multitaper technique, and performance was analyzed
      when limiting the size of the parameter-estimation region. Errors were quantified
      by the bias and standard deviation of the alpha0 and beta estimates, and by the
      overall power-law fit error (FE). For parameter estimation regions larger than
      ~34 pulse lengths (~1 cm for this experiment), an overall power-law FE of 4% was
      achieved with all spectral estimation methods. With smaller parameter estimation
      regions as in parametric image formation, the bias and standard deviation of the
      alpha0 and beta estimates depended on the size of the parameter estimation
      region. Here, the multitaper method reduced the standard deviation of the alpha0
      and beta estimates compared with those using the other techniques. The results
      provide guidance for choosing methods for estimating the power spectral density
      in quantitative ultrasound methods. 

PMID- 23858057
TI  - CD81 controls sustained T cell activation signaling and defines the maturation
      stages of cognate immunological synapses.
AB  - In this study, we investigated the dynamics of the molecular interactions of
      tetraspanin CD81 in T lymphocytes, and we show that CD81 controls the
      organization of the immune synapse (IS) and T cell activation. Using quantitative
      microscopy, including fluorescence recovery after photobleaching (FRAP), phasor
      fluorescence lifetime imaging microscopy-Foster resonance energy transfer
      (phasorFLIM-FRET), and total internal reflection fluorescence microscopy (TIRFM),
      we demonstrate that CD81 interacts with ICAM-1 and CD3 during conjugation between
      T cells and antigen-presenting cells (APCs). CD81 and ICAM-1 exhibit distinct
      mobilities in central and peripheral areas of early and late T cell-APC contacts.
      Moreover, CD81-ICAM-1 and CD81-CD3 dynamic interactions increase over the time
      course of IS formation, as these molecules redistribute throughout the contact
      area. Therefore, CD81 associations unexpectedly define novel sequential steps of
      IS maturation. Our results indicate that CD81 controls the temporal progression
      of the IS and the permanence of CD3 in the membrane contact area, contributing to
      sustained T cell receptor (TCR)-CD3-mediated signaling. Accordingly, we find that
      CD81 is required for proper T cell activation, regulating CD3zeta, ZAP-70, LAT,
      and extracellular signal-regulated kinase (ERK) phosphorylation; CD69 surface
      expression; and interleukin-2 (IL-2) secretion. Our data demonstrate the
      important role of CD81 in the molecular organization and dynamics of the IS
      architecture that sets the signaling threshold in T cell activation. 

PMID- 23858058
TI  - Insulin inhibits lipolysis in adipocytes via the evolutionarily conserved mTORC1
      Egr1-ATGL-mediated pathway.
AB  - One of the basic functions of insulin in the body is to inhibit lipolysis in
      adipocytes. Recently, we have found that insulin inhibits lipolysis and promotes
      triglyceride storage by decreasing transcription of adipose triglyceride lipase
      via the mTORC1-mediated pathway (P. Chakrabarti et al., Diabetes 59:775-781,
      2010), although the mechanism of this effect remained unknown. Here, we used a
      genetic screen in Saccharomyces cerevisiae in order to identify a transcription
      factor that mediates the effect of Tor1 on the expression of the ATGL ortholog in
      yeast. This factor, Msn4p, has homologues in mammalian cells that form a family
      of early growth response transcription factors. One member of the family, Egr1,
      is induced by insulin and nutrients and directly inhibits activity of the ATGL
      promoter in vitro and expression of ATGL in cultured adipocytes. Feeding animals
      a high-fat diet increases the activity of mTORC1 and the expression of Egr1 while
      decreasing ATGL levels in epididymal fat. We suggest that the evolutionarily
      conserved mTORC1-Egr1-ATGL regulatory pathway represents an important component
      of the antilipolytic effect of insulin in the mammalian organism. 

PMID- 23858059
TI  - Parkin-dependent degradation of the F-box protein Fbw7beta promotes neuronal
      survival in response to oxidative stress by stabilizing Mcl-1.
AB  - Parkinson's disease (PD) is characterized by progressive loss of midbrain
      dopaminergic neurons resulting in motor dysfunction. While most PD is sporadic in
      nature, a significant subset can be linked to either dominant or recessive germ
      line mutations. PARK2, encoding the ubiquitin ligase parkin, is the most
      frequently mutated gene in hereditary Parkinson's disease. Here, we present
      evidence for a neuronal ubiquitin ligase cascade involving parkin and the
      multisubunit ubiquitin ligase SCF(Fbw7beta). Specifically, parkin targets the SCF
      substrate adapter Fbw7beta for proteasomal degradation. Furthermore, we show that
      the physiological role of parkin-mediated regulation of Fbw7beta levels is the
      stabilization of the mitochondrial prosurvival factor Mcl-1, an SCF(Fbw7beta)
      target in neurons. We show that neurons depleted of parkin become acutely
      sensitive to oxidative stress due to an inability to maintain adequate levels of
      Mcl-1. Therefore, loss of parkin function through biallelic mutation of PARK2 may
      lead to death of dopaminergic neurons through unregulated SCF(Fbw7beta)-mediated
      ubiquitylation-dependent proteolysis of Mcl-1. 

PMID- 23858061
TI  - Generation of the blaCTX-M-116 hybrid gene.

PMID- 23858060
TI  - Self-association of the Gal4 inhibitor protein Gal80 is impaired by Gal3:
      evidence for a new mechanism in the GAL gene switch.
AB  - The DNA-binding transcriptional activator Gal4 and its regulators Gal80 and Gal3
      constitute a galactose-responsive switch for the GAL genes of Saccharomyces
      cerevisiae. Gal4 binds to GAL gene UASGAL (upstream activation sequence in GAL
      gene promoter) sites as a dimer via its N-terminal domain and activates
      transcription via a C-terminal transcription activation domain (AD). In the
      absence of galactose, a Gal80 dimer binds to a dimer of Gal4, masking the Gal4AD.
      Galactose triggers Gal3-Gal80 interaction to rapidly initiate Gal4-mediated
      transcription activation. Just how Gal3 alters Gal80 to relieve Gal80 inhibition
      of Gal4 has been unknown, but previous analyses of Gal80 mutants suggested a
      possible competition between Gal3-Gal80 and Gal80 self-association interactions.
      Here we assayed Gal80-Gal80 interactions and tested for effects of Gal3.
      Immunoprecipitation, cross-linking, and denaturing and native PAGE analyses of
      Gal80 in vitro and fluorescence imaging of Gal80 in live cells show that Gal3
      Gal80 interaction occurs concomitantly with a decrease in Gal80 multimers.
      Consistent with this, we find that newly discovered nuclear clusters of Gal80
      dissipate in response to galactose-triggered Gal3-Gal80 interaction. We discuss
      the effect of Gal3 on the quaternary structure of Gal80 in light of the evidence
      pointing to multimeric Gal80 as the form required to inhibit Gal4. 

PMID- 23858062
TI  - Reply to "Generation of the blaCTX-M-116 hybrid gene".

PMID- 23858064
TI  - Reply to "Are there reasons to prefer tetracyclines to macrolides in older
      patients with community-acquired pneumonia?".

PMID- 23858063
TI  - Are there reasons to prefer tetracyclines to macrolides in older patients with
      community-acquired pneumonia?

PMID- 23858067
TI  - Predictors of depressive symptoms among Hispanic women in South Florida.
AB  - U.S. Hispanics, especially women, experience a disproportionate amount of disease
      burden for depression. This disparity among Hispanic women necessitates
      examination of factors associated with depression. The objective of this study
      was to use an adaptation of the Stress Process Model to test whether self-esteem
      mediated the relationship between Hispanic stress and depressive symptoms. Data
      for this secondary analysis were from a previous randomized-control HIV
      prevention trial. Participants were 548 Hispanic women (19-52 years). Data
      collection measures included the Center for Epidemiological Studies-Depression
      Scale, Rosenberg Self-Esteem Scale, and Hispanic Stress Scale. The bootstrap
      method in Mplus 6 was used to test mediation. Results indicated that self-esteem
      was inversely related to depression, and Hispanic stress was found to be
      positively related to depression. Self-esteem partially mediated the relationship
      between stress and depression. Strategies to improve/maintain self-esteem should
      be considered in future interventions for Hispanic women with depression.

PMID- 23858068
TI  - Coexisting addiction and pain in people receiving methadone for addiction.
AB  - The aim of this qualitative study was to examine the narratives of people who
      experience chronic pain (lasting 6 months or more) and were receiving methadone
      for the treatment of their opiate addiction through a major methadone clinic.
      This paper featured the pathway of how the participants developed chronic pain
      and addiction, and their beliefs of how prescription opioids would impact their
      addiction in the future. Thirty-four participants who experienced chronic pain
      and received methadone for treatment of opiate addiction were willing to tell the
      story of their experiences. The findings in three areas are presented: (a)
      whether participants experienced addiction first or pain first and how their
      exposures to addictive substances influenced their experiences, (b) the
      significance of recreational drug use and patterns of abuse behaviors leading to
      chronic pain, and (c) participants' experiences and beliefs about the potential
      for abuse of prescription opioid used for treatment of pain. 

PMID- 23858069
TI  - Simultaneous emergence of several biotypes of Brucella among Baotou's brucellosis
      patients by combined diagnostic strategy.

PMID- 23858070
TI  - Stopping trials early.

PMID- 23858071
TI  - Is sedation by non-anaesthetists really safe?

PMID- 23858072
TI  - Next on the agenda: gender.

PMID- 23858073
TI  - Pneumothorax and cardiac arrest caused by speaking valve mistaken as moisture
      exchanger: an incident report.

PMID- 23858074
TI  - Psoas compartment block for anaesthesia during surgical repair of inguinal
      hernias.

PMID- 23858075
TI  - New method of percutaneous radiofrequency mandibular nerve rhizotomy guided by
      high-speed real-time computed tomography fluoroscopy with direct approaching view
      to foramen ovale.

PMID- 23858076
TI  - Anaesthetic staff cannot identify extremely high tracheal tube cuff pressures by
      palpation of the pilot balloon.

PMID- 23858077
TI  - Paracetamol or metronidazole?

PMID- 23858078
TI  - Topical lidocaine to suppress trigemino-cardiac reflex.

PMID- 23858079
TI  - Emergency reversal of heparin overdose in a neurosurgical patient guided by
      thromboelastography.

PMID- 23858080
TI  - International practices of organ donation: an alternative view of Australian
      experiences.

PMID- 23858087
TI  - Education quality, reading recognition, and racial differences in the
      neuropsychological outcome from traumatic brain injury.
AB  - Ethnically diverse examinees tend to perform lower on neuropsychological tests.
      The practice of adjusting normative comparisons for the education level and/or
      race to prevent overpathologizing low scores is problematic. Education quality,
      as measured by reading recognition, appears to be a more accurate benchmark for
      premorbid functioning in certain populations. The present study aimed to extend
      this line of research to traumatic brain injury (TBI). We hypothesized that a
      measure of reading recognition, the Wechsler Test of Adult Reading (WTAR), would
      account for racial differences in neuropsychological performance after TBI. Fifty
      participants (72% African American, 28% Caucasian) with moderate to severe TBI
      underwent neuropsychological testing at 1-year post-injury. Reading recognition
      accounted for all the same variance in neuropsychological performance as race and
      education (together), as well as considerable additional variance. Estimation of
      premorbid functioning in African Americans with TBI could be refined by
      considering reading recognition. 

PMID- 23858088
TI  - Revised mechanism of D-alanine incorporation into cell wall polymers in Gram
      positive bacteria.
AB  - Teichoic acids (TAs) are important for growth, biofilm formation, adhesion and
      virulence of Gram-positive bacterial pathogens. The chemical structures of the
      TAs vary between bacteria, though they typically consist of zwitterionic polymers
      that are anchored to either the peptidoglycan layer as in the case of wall
      teichoic acid (WTA) or the cell membrane and named lipoteichoic acid (LTA). The
      polymers are modified with D-alanines and a lack of this decoration leads to
      increased susceptibility to cationic antimicrobial peptides. Four proteins, DltA
      D, are essential for the incorporation of d-alanines into cell wall polymers and
      it has been established that DltA transfers D-alanines in the cytoplasm of the
      cell onto the carrier protein DltC. However, two conflicting models have been
      proposed for the remainder of the mechanism. Using a cellular protein
      localization and membrane topology analysis, we show here that DltC does not
      traverse the membrane and that DltD is anchored to the outside of the cell. These
      data are in agreement with the originally proposed model for D-alanine
      incorporation through a process that has been proposed to proceed via a D-alanine
      undecaprenyl phosphate membrane intermediate. Furthermore, we found that WTA
      isolated from a Staphylococcus aureus strain lacking LTA contains only a small
      amount of D-alanine, indicating that LTA has a role, either direct or indirect,
      in the efficient D-alanine incorporation into WTA in living cells.

PMID- 23858089
TI  - Red meat, dietary heme iron, and risk of type 2 diabetes: the involvement of
      advanced lipoxidation endproducts.
AB  - There is growing evidence of disordered iron homeostasis in the diabetic
      condition, with links proposed between dietary iron intakes and both the risk of
      disease and the risk of complications of advanced disease. In the United States,
      Britain, and Canada, the largest dietary contributors of iron are cereals and
      cereal products and meat and meat products. This review discusses the findings of
      cohort studies and meta-analyses of heme iron and red meat intakes and the risk
      of type 2 diabetes. These suggest that processed red meat is associated with
      increased risk, with high intakes of red meat possibly also associated with a
      small increased risk. Historically, humans have relied on large quantities of
      heme iron and red meat in their diets, and therefore it is paradoxical that iron
      from meat sources should be associated with the risk of type 2 diabetes. A reason
      for this association may be drawn from studies of dietary advanced glycation and
      lipoxidation endproducts present in processed food and the mechanisms by which
      insulin output by pancreatic islet cells might be influenced by the protein
      modifications present in processed red meat. 

PMID- 23858090
TI  - miRNA analysis for the assessment of exercise and amino acid effects on human
      skeletal muscle.
AB  - The study of micro RNA (miRNA) expression and function, a largely unexplored area
      of human muscle biology, may provide novel data regarding the development of
      targeted approaches that optimize skeletal muscle responses to exercise and amino
      acid manipulations. miRNAs are ubiquitously expressed, small noncoding RNAs that
      modulate posttranscriptional gene expression. Quantifying miRNA expression and
      predicting function as regulators of both single targets and complex networks is
      technically challenging and requires a combined approach of bioinformatics,
      molecular, and systems biology. Recent evidence suggests that the expression of
      muscle-specific miRNAs (myomirs), including miR-1, miR-133a/b, miR-206, and miR
      499, is modulated by essential amino acid ingestion, endurance exercise, and
      endurance exercise training. The expression of miRNAs has also been implicated in
      the anabolic intracellular signaling and muscle hypertrophic response associated
      with resistance exercise training. Although these findings are intriguing,
      comprehensive human trials assessing functional outcomes associated with changes
      in miRNA expression in response to exercise and nutrition interventions have not
      been conducted. This article reviews the current understanding of miRNA biology
      and includes analytical techniques used to detect miRNA expression and methods to
      predict function. The intent is to provide the framework for future research
      studies that use miRNA analysis in an effort to elucidate optimal exercise and
      nutritional countermeasures for the prevention of muscle loss. 

PMID- 23858091
TI  - Effect of dairy proteins on appetite, energy expenditure, body weight, and
      composition: a review of the evidence from controlled clinical trials.
AB  - Evidence supports that a high proportion of calories from protein increases
      weight loss and prevents weight (re)gain. Proteins are known to induce satiety,
      increase secretion of gastrointestinal hormones, and increase diet-induced
      thermogenesis, but less is known about whether various types of proteins exert
      different metabolic effects. In the Western world, dairy protein, which consists
      of 80% casein and 20% whey, is a large contributor to our daily protein intake.
      Casein and whey differ in absorption and digestion rates, with casein being a
      "slow" protein and whey being a "fast" protein. In addition, they differ in amino
      acid composition. This review examines whether casein, whey, and other protein
      sources exert different metabolic effects and targets to clarify the underlying
      mechanisms. Data indicate that whey is more satiating in the short term, whereas
      casein is more satiating in the long term. In addition, some studies indicate
      that whey stimulates the secretion of the incretin hormones glucagon-like peptide
      1 and glucose-dependent insulinotropic polypeptide more than other proteins.
      However, for the satiety (cholecystokinin and peptide YY) and hunger-stimulating
      (ghrelin) hormones, no clear evidence exists that 1 protein source has a greater
      stimulating effect compared with others. Likewise, no clear evidence exists that
      1 protein source results in higher diet-induced thermogenesis and promotes more
      beneficial changes in body weight and composition compared with other protein
      sources. However, data indicate that amino acid composition, rate of absorption,
      and protein/food texture may be important factors for protein-stimulated
      metabolic effects. 

PMID- 23858093
TI  - Natural vitamin D content in animal products.
AB  - Humans derive most vitamin D from the action of sunlight in their skin. However,
      in view of the current Western lifestyle with most daily activities taking place
      indoors, sun exposure is often not sufficient for adequate vitamin D production.
      For this reason, dietary intake is also of great importance. Animal foodstuffs
      (e.g., fish, meat, offal, egg, dairy) are the main sources for naturally
      occurring cholecalciferol (vitamin D-3). This paper therefore aims to provide an
      up-to-date overview of vitamin D-3 content in various animal foods. The focus
      lies on the natural vitamin D-3 content because there are many countries in which
      foods are not regularly fortified with vitamin D. The published data show that
      the highest values of vitamin D are found in fish and especially in fish liver,
      but offal also provides considerable amounts of vitamin D. The content in muscle
      meat is generally much lower. Vitamin D concentrations in egg yolks range between
      the values for meat and offal. If milk and dairy products are not fortified, they
      are normally low in vitamin D, with the exception of butter because of its high
      fat content. However, as recommendations for vitamin D intake have recently been
      increased considerably, it is difficult to cover the requirements solely by
      foodstuffs. 

PMID- 23858092
TI  - PPAR-alpha as a key nutritional and environmental sensor for metabolic
      adaptation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are transcription factors
      that belong to the superfamily of nuclear hormone receptors and regulate the
      expression of several genes involved in metabolic processes that are potentially
      linked to the development of some diseases such as hyperlipidemia, diabetes, and
      obesity. One type of PPAR, PPAR-alpha, is a transcription factor that regulates
      the metabolism of lipids, carbohydrates, and amino acids and is activated by
      ligands such as polyunsaturated fatty acids and drugs used to treat
      dyslipidemias. There is evidence that genetic variants within the PPARalpha gene
      have been associated with a risk of the development of dyslipidemia and
      cardiovascular disease by influencing fasting and postprandial lipid
      concentrations; the gene variants have also been associated with an acceleration
      of the progression of type 2 diabetes. The interactions between genetic PPARalpha
      variants and the response to dietary factors will help to identify individuals or
      populations who can benefit from specific dietary recommendations. Interestingly,
      certain nutritional conditions, such as the prolonged consumption of a protein
      restricted diet, can produce long-lasting effects on PPARalpha gene expression
      through modifications in the methylation of a specific locus surrounding the
      PPARalpha gene. Thus, this review underlines our current knowledge about the
      important role of PPAR-alpha as a mediator of the metabolic response to
      nutritional and environmental factors. 

PMID- 23858095
TI  - Carotenoids.

PMID- 23858096
TI  - IOM (Institute of Medicine) and NRC (National Research Council). 2013.
      Supplemental Nutrition Assistance Program: Examining the Evidence to Define
      Benefit Adequacy. Washington, DC: The National Academies Press, 2013.

PMID- 23858094
TI  - Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented
      food products to vitamin K requirements.
AB  - Vitamin K exists in the food supply as phylloquinone, a plant-based form and as
      menaquinones (MKs), a collection of isoprenologues mostly originating from
      bacterial synthesis. Although multiple bacterial species used as starter cultures
      for food fermentations synthesize MK, relatively little is known about the
      presence and distribution of MK in the food supply and the relative contribution
      of MK to total dietary vitamin K intake. Dairy products may be a predominant
      source of dietary MK in many regions of the world, and there is recent interest
      in enhancing the MK content of dairy products through identification and
      selection of MK-producing bacteria in dairy fermentations. This interest is
      increased by emerging evidence that current dietary recommendations based on the
      classic role of vitamin K as an enzyme cofactor for coagulation proteins may not
      be optimal for supporting vitamin K requirements in extrahepatic tissues and that
      MK may have unique bioactivity beyond that as an enzyme cofactor. Observational
      studies have reported favorable associations between MK intake and bone and
      cardiovascular health. Although randomized trials have provided some evidence to
      support the beneficial effects of MK on bone, the evidence to date is not
      definitive, and randomized trials have not yet examined MK intake in relation to
      cardiovascular outcomes. Food production practices provide a means to enhance
      dietary MK availability and intake. However, parallel research is needed to
      optimize these production practices, develop comprehensive food MK content
      databases, and test hypotheses of unique beneficial physiological roles of MK
      beyond that achieved by phylloquinone. 

PMID- 23858099
TI  - Minocycline targets the NF-kappaB Nexus through suppression of TGF-beta1-TAK1
      IkappaB signaling in ovarian cancer.
AB  - Substantial evidence supports the critical role of NF-kappaB in ovarian cancer.
      Minocycline, a tetracycline, has been shown to exhibit beneficial effects in this
      malignancy through regulation of a cohort of genes that overlap significantly
      with the NF-kappaB transcriptome. Here, it was examined whether or not the
      molecular mechanism could be attributed to modulation of NF-kappaB signaling
      using a combination of in vitro and in vivo models. Minocycline suppressed
      constitutive NF-kappaB activation in OVCAR-3 and SKOV-3 ovarian carcinoma cells
      and was correlated with attenuation of IkappaBalpha kinase (IKK) activation,
      IkappaBalpha phosphorylation and degradation, and p65 phosphorylation and nuclear
      translocation. The inhibition of IKK was found to be associated with suppression
      of TGF-beta-activated-kinase-1 (TAK1) activation and its dissociation from TAK1
      binding-protein-1 (TAB1), an indispensable functional mediator between TGF-beta
      and TAK1. Further studies demonstrated that minocycline downregulated TGF-beta1
      expression. Enforced TGF-beta1 expression induced NF-kappaB activity, and
      minocycline rescued this effect. Consistent with this finding, TGF-beta1
      knockdown suppressed NF-kappaB activation and abrogated the inhibitory effect of
      minocycline on this transcription factor. These results suggest that the
      minocycline-induced suppression of NF-kappaB activity is mediated, in part,
      through inhibition of TGF-beta1. Furthermore, the influence of minocycline on NF
      kappaB pathway activation was examined in female nude mice harboring
      intraperitoneal OVCAR-3 tumors. Both acute and chronic administration of
      minocycline led to suppression of p65 phosphorylation and nuclear translocation
      accompanied by downregulation of NF-kappaB activity and endogenous protein levels
      of its target gene products. These data reveal the therapeutic potential of
      minocycline as an agent targeting the pro-oncogenic TGF-beta-NF-kappaB axis in
      ovarian cancer. IMPLICATIONS: This preclinical study lends support to the notion
      that ovarian cancer management would benefit from administration of minocycline.

PMID- 23858098
TI  - 53BP1 is limiting for NHEJ repair in ATM-deficient model systems that are
      subjected to oncogenic stress or radiation.
AB  - The DNA damage response (DDR) factors ataxia telangiectasia mutated (ATM) and p53
      binding protein 1 (53BP1) function as tumor suppressors in humans and mice, but
      the significance of their mutual interaction to the suppression of oncogenic
      translocations in vivo has not been investigated. To address this question, the
      phenotypes of compound mutant mice lacking 53BP1 and ATM (Trp53bp1(-/-)/Atm(-/
      )), relative to single mutants, were examined. These analyses revealed that loss
      of 53BP1 markedly decreased the latency of T-lineage lymphomas driven by RAG
      dependent oncogenic translocations in Atm(-/-) mice (average survival, 14 and 23
      weeks for Trp53bp1(-/-)/Atm(-/-) and Atm(-/-) mice, respectively).
      Mechanistically, 53BP1 deficiency aggravated the deleterious effect of ATM
      deficiency on nonhomologous end-joining (NHEJ)-mediated double-strand break
      repair. Analysis of V(D)J recombinase-mediated coding joints and signal joints in
      Trp53bp1(-/-)/Atm(-/-) primary thymocytes is, however, consistent with canonical
      NHEJ-mediated repair. Together, these findings indicate that the greater NHEJ
      defect in the double mutant mice resulted from decreased efficiency of rejoining
      rather than switching to an alternative NHEJ-mediated repair mechanism.
      Complementary analyses of irradiated primary cells indicated that defects in cell
      cycle checkpoints subsequently function to amplify the NHEJ defect, resulting in
      more frequent chromosomal breaks and translocations in double mutant cells
      throughout the cell cycle. Finally, it was determined that 53BP1 is dispensable
      for the formation of RAG-mediated hybrid joints in Atm(-/-) thymocytes but is
      required to suppress large deletions in a subset of hybrid joints. IMPLICATIONS:
      The current study uncovers novel ATM-independent functions for 53BP1 in the
      suppression of oncogenic translocations and in radioprotection.

PMID- 23858100
TI  - Coronary vasomotor response to intracoronary acetylcholine injection, clinical
      features, and long-term prognosis in 873 consecutive patients with coronary
      spasm: analysis of a single-center study over 20 years.
AB  - BACKGROUND: The aim of this study was to elucidate the correlation between
      angiographic coronary vasomotor responses to intracoronary acetylcholine (ACh)
      injection, clinical features, and long-term prognosis in patients with
      vasospastic angina (VSA). METHODS AND RESULTS: This is a retrospective,
      observational, single-center study of 1877 consecutive patients who underwent ACh
      provocation test between January 1991 and December 2010. ACh-provoked coronary
      spasm was observed in 873 of 1637 patients included in the present analysis. ACh
      positive patients were more likely to be older male smokers with dyslipidemia, to
      have a family history of ischemic heart disease, and to have a comorbidity of
      coronary epicardial stenosis than were ACh-negative patients. ACh-positive
      patients were divided into 2 groups: those with focal (total or subtotal
      obstruction, n=511) and those with diffuse (severe diffuse vasoconstriction,
      n=362) spasm patterns. Multivariable logistic regression analysis identified
      female sex and low comorbidity of coronary epicardial stenosis to correlate with
      the ACh-provoked diffuse spasm pattern in patients with VSA. Kaplan-Meier
      survival curve indicated better 5-year survival rates free from major adverse
      cardiovascular events in patients with diffuse spasm pattern compared with those
      with focal spasm pattern (P=0.019). Multivariable Cox hazard regression analysis
      identified diffuse spasm pattern as a negative predictor of major adverse
      cardiovascular events in patients with VSA. CONCLUSIONS: ACh-induced diffuse
      coronary spasm was frequently observed in female VSA patients free of severe
      coronary epicardial stenosis and was associated with better prognosis than focal
      spasm. These results suggest the need to identify the ACh-provoked coronary spasm
      subtypes in patients with VSA.

PMID- 23858101
TI  - NF1 deletion generates multiple subtypes of soft-tissue sarcoma that respond to
      MEK inhibition.
AB  - Soft-tissue sarcomas are a heterogeneous group of tumors arising from connective
      tissue. Recently, mutations in the neurofibromin 1 (NF1) tumor suppressor gene
      were identified in multiple subtypes of human soft-tissue sarcomas. To study the
      effect of NF1 inactivation in the initiation and progression of distinct sarcoma
      subtypes, we have developed a novel mouse model of temporally and spatially
      restricted NF1-deleted sarcoma. To generate primary sarcomas, we inject
      adenovirus containing Cre recombinase into NF1(flox/flox); Ink4a/Arf(flox/flox)
      mice at two distinct orthotopic sites: intramuscularly or in the sciatic nerve.
      The mice develop either high-grade myogenic sarcomas or malignant peripheral
      nerve sheath tumor (MPNST)-like tumors, respectively. These tumors reflect the
      histologic properties and spectrum of sarcomas found in patients. To explore the
      use of this model for preclinical studies, we conducted a study of mitogen
      activated protein kinase (MAPK) pathway inhibition with the MEK inhibitor
      PD325901. Treatment with PD325901 delays tumor growth through decreased cyclin D1
      mRNA and cell proliferation. We also examined the effects of MEK inhibition on
      the native tumor stroma and find that PD325901 decreases VEGFalpha expression in
      tumor cells with a corresponding decrease in microvessel density. Taken together,
      our results use a primary tumor model to show that sarcomas can be generated by
      loss of NF1 and Ink4a/Arf, and that these tumors are sensitive to MEK inhibition
      by direct effects on tumor cells and the surrounding microenvironment. These
      studies suggest that MEK inhibitors should be further explored as potential
      sarcoma therapies in patients with tumors containing NF1 deletion.

PMID- 23858242
TI  - Mental health concepts in India: Providing valuable insights.

PMID- 23858102
TI  - The functionalized human serine protease granzyme B/VEGF121 targets tumor
      vasculature and ablates tumor growth.
AB  - The serine protease granzyme B (GrB) induces apoptosis through both caspase
      dependent and -independent multiple-cascade mechanisms. VEGF121 binds to both
      VEGF receptor (VEGFR)-1 and VEGFR-2 receptors. We engineered a unique GrB/VEGF121
      fusion protein and characterized its properties in vitro and in vivo. Endothelial
      and tumor cell lines showed varying levels of sensitivity to GrB/VEGF121 that
      correlated closely to total VEGFR-2 expression. GrB/VEGF121 localized efficiently
      into VEGFR-2-expressing cells, whereas the internalization into VEGFR-1
      expressing cells was significantly reduced. Treatment of VEGFR-2(+) cells caused
      mitochondrial depolarization in 48% of cells by 48 hours. Exposure to GrB/VEGF121
      induced apoptosis in VEGFR-2(+), but not in VEGFR-1(+), cells and rapid caspase
      activation was observed that could not be inhibited by treatment with a pan
      caspase inhibitor. In vivo, GrB/VEGF121 localized in perivascular tumor areas
      adjacent to microvessels and in other areas in the tumor less well vascularized,
      whereas free GrB did not specifically localize to tumor tissue. Administration
      (intravenous) of GrB/VEGF121 to mice at doses up to 40 mg/kg showed no toxicity.
      Treatment of mice bearing established PC-3 tumor xenografts with GrB/VEGF121
      showed significant antitumor effect versus treatment with GrB or saline.
      Treatment with GrB/VEGF121 at 27 mg/kg resulted in the regression of four of five
      tumors in this group. Tumors showed a two-fold lower Ki-67-labeling index
      compared with controls. Our results show that targeted delivery of GrB to tumor
      vascular endothelial cells or to tumor cells activates apoptotic cascades and
      this completely human construct may have significant therapeutic potential.

PMID- 23858103
TI  - Conserved tryptophan residues within putative transmembrane domain 6 affect
      transport function of organic anion transporting polypeptide 1B1.
AB  - The organic anion-transporting polypeptides (OATPs, gene symbol SLCO) are a
      family of transporters that play important roles in the absorption, distribution,
      metabolism, and excretion of various drugs. Although substrate specificity of
      transporter proteins is under extensive study, the underlying mechanisms for
      substrate binding and/or recognition remain largely unknown. Transmembrane domain
      6 (TM6) is a relatively conserved region within OATP family members, and several
      amino acid residues on its extracellular half are part of the OATP family
      signature sequence D-X-RW-(I,V)-GAWWX-G-(F,L)-L. In the present study, two
      adjacent tryptophan residues (Trp258 and Trp259) within TM6 were identified as
      critical amino acids for the transport function of OATP1B1. Kinetic studies
      showed that substitution of Trp258 with alanine resulted in monophasic kinetics
      for estrone-3-sulfate uptake, with a significantly higher Km value (Km = 12.0 +/-
      2.8 MUM) than the high-affinity component of wild-type OATP1B1 (Km = 0.38 +/-
      0.06 MUM). On the other hand, W259A retained the biphasic characteristic of the
      transporter. Km values of the high- and low-affinity components for estrone-3
      sulfate of W259A are 1.93 +/- 0.76 MUM and 30.8 +/- 4.4 MUM, respectively.
      Further studies revealed that W258A retained transport function of another
      prototypic substrate, taurocholate, while W259A displayed a dramatically reduced
      uptake of the substrate and exhibited an 8-fold increase in the Km value compared
      with that of the wild-type and W258A. Our results suggest that Trp258 and Trp259
      may play different roles in the uptake of different substrates by OATP1B1. 

PMID- 23858243
TI  - Indian mental concepts: Looking forward.

PMID- 23858244
TI  - Indianization of psychiatry utilizing Indian mental concepts.
AB  - Most of the psychiatry practice in India is guided by the western concepts of
      mental health and illness, which have largely ignored the role of religion,
      family, eastern philosophy, and medicine in understanding and managing the
      psychiatric disorders. India comprises of diverse cultures, languages,
      ethnicities, and religious affiliations. However, besides these diversities,
      there are certain commonalities, which include Hinduism as a religion which is
      spread across the country, the traditional family system, ancient Indian system
      of medicine and emphasis on use of traditional methods like Yoga and Meditation
      for controlling mind. This article discusses as to how mind and mental health are
      understood from the point of view of Hinduism, Indian traditions and Indian
      systems of medicine. Further, the article focuses on as to how these Indian
      concepts can be incorporated in the practice of contemporary psychiatry. 

PMID- 23858245
TI  - Yoga school of thought and psychiatry: Therapeutic potential.
AB  - Yoga is a traditional life-style practice used for spiritual reasons. However,
      the physical components like the asanas and pranayaamas have demonstrated
      physiological and therapeutic effects. There is evidence for Yoga as being a
      potent antidepressant that matches with drugs. In depressive disorder, yoga
      'corrects' an underlying cognitive physiology. In schizophrenia patients, yoga
      has benefits as an add-on intervention in pharmacologically stabilized subjects.
      The effects are particularly notable on negative symptoms. Yoga also helps to
      correct social cognition. Yoga can be introduced early in the treatment of
      psychosis with some benefits. Elevation of oxytocin may be a mechanism of yoga
      effects in schizophrenia. Certain components of yoga have demonstrated
      neurobiological effects similar to those of vagal stimulation, indicating this
      (indirect or autogenous vagal stimulation) as a possible mechanism of its action.
      It is time, psychiatrists exploited the benefits if yoga for a comprehensive care
      in their patients. 

PMID- 23858246
TI  - Karma yoga: A path towards work in positive psychology.
AB  - Karma yoga is the path that leads to salvation through action. Salvation is the
      ultimate state of consciousness. Work is the central and defining characteristic
      of life. It may have intrinsic value, instrumental value, or both. Instrumental
      value includes incentive, dignity and power, etc., which is the result expected
      from the work. The Gita teaches us to do work without thinking of result (work
      with intrinsic value). Attachment with the result leads to stress, competition
      and aggression. Stress further gives rise to heart ailments, depression and
      suicide. Positive psychology studies the factors and conditions leading to
      pleasurable and satisfying life. Understanding Karma yoga and its practice has a
      similar role that lead an individual towards work and leading to a satisfied
      life. This may play a unique role towards practical aspects of positive
      psychology to improve one's lifestyle and aid in the treatment of stress
      disorders. 

PMID- 23858247
TI  - Emotions: An Indian perspective.
AB  - The present paper is an attempt to understand emotions and the affect from Indian
      traditional point of view. In the Indian philosophical texts' detailed
      descriptions of emotions are not available nor are dealt with as a separate
      concept. This view of emotions lays emphasis on desires as the root cause of
      emotional upheavals. They are seen as modification of desire and attachment. The
      desires are seen as arising from the contact and attachment of the ego or
      ahamkara with the external world and are caused by a sense of imperfection,
      incompleteness or non-fulfillment. Ego or ahamkara is differentiated from the
      true Self or atman. Emotions are viewed as springs of action and are bipolar in
      nature. According to Patanjali's Yoga Shastra, suffering is due to ignorance
      about one's true "self" (avidya). Hence, suffering or dukha arises from within
      and not from the outside world. Bhagvadgita traces all emotional experiences to
      the gunas, i.e., sattva, rajas, and tamas. Works of Bharathmuni have contributed
      to the understanding of emotional experiences. Concept of rasa or aesthetic
      relish is central to this approach to understanding affective experiences as
      dealt with in the Natyashastra of Bharathamuni. These views underline the
      recommended path for self-transformation. Regulating emotions, both emotional
      experience and emotional expression, is an integral part of the recommended
      "principles of living." 

PMID- 23858248
TI  - Clinical hypnosis and Patanjali yoga sutras.
AB  - The trance states in yoga and hypnosis are associated with similar phenomena like
      relaxation, disinclination to talk, unreality, misrepresentation, alterations in
      perception, increased concentration, suspension of normal reality testing, and
      the temporary nature of the phenomena. While some researchers consider yoga to be
      a form of hypnosis, others note that there are many similarities between the
      trance in yoga and the hypnotic trance. The present study aimed to find
      similarities between the trance states of hypnosis and Patanjali's yoga sutras.
      The trance states were compared with the understanding of the phenomena of
      trance, and the therapeutic techniques and benefits of both. An understanding of
      the concept of trance in Patanjali's yoga sutras was gained through a thematic
      analysis of the book Four Chapters on Freedom by Swami Satyananda Saraswati. This
      led to an understanding of the concept of trance in the yoga sutras. The obtained
      concepts were compared to the concepts of trance in hypnosis (obtained through
      the literature on hypnosis) to investigate whether or not there exist
      similarities. The findings of the study show that there are similarities between
      the trance in hypnosis and the trance in Patanjali's yoga sutras in the induction
      and deepening of the trance states in hypnosis and that of Samadhi, the phenomena
      present in hypnosis and the kinds of siddhis that are obtained through Samadhi,
      and the therapeutic techniques and the therapeutic process in Patanjali's yoga
      sutra and hypnosis. 

PMID- 23858249
TI  - Buddha philosophy and western psychology.
AB  - Four noble truths as preached by Buddha are that the life is full of suffering
      (Duhkha), that there is a cause of this suffering (Duhkha-samudaya), it is
      possible to stop suffering (Duhkha-nirodha), and there is a way to extinguish
      suffering (Duhkha-nirodha-marga). Eight fold Path (astangika-marga) as advocated
      by Buddha as a way to extinguish the sufferings are right views, right
      resolve/aspiration, right speech, right action/conduct, right livelihood, right
      effort right mindfulness and right concentration. Mid-twentieth century saw the
      collaborations between many psychoanalysts and Buddhist scholars as a meeting
      between "two of the most powerful forces" operating in the Western mind. Buddhism
      and Western Psychology overlap in theory and in practice. Over the last century,
      experts have written on many commonalities between Buddhism and various branches
      of modern western psychology like phenomenological psychology, psychoanalytical
      psychotherapy, humanistic psychology, cognitive psychology and existential
      psychology. Orientalist Alan Watts wrote 'if we look deeply into such ways of
      life as Buddhism, we do not find either philosophy or religion as these are
      understood in the West. We find something more nearly resembling psychotherapy'.
      Buddha was a unique psychotherapist. His therapeutic methods helped millions of
      people throughout the centuries. This essay is just an expression of what little
      the current author has understood on Buddha philosophy and an opportunity to
      offer his deep tribute to one of the greatest psychotherapists the world has ever
      produced! 

PMID- 23858250
TI  - The mystery of reincarnation.
AB  - One of the mysteries puzzling human mind since the origin of mankind is the
      concept of "reincarnation" which literally means "to take on the flesh again." As
      the civilizations evolved, beliefs got discriminated and disseminated into
      various religions. The major division manifested was "East" and "West." The
      eastern religions being more philosophical and less analytical, have accepted
      reincarnation. However, the different eastern religions like Hinduism, Jainism,
      and Buddhism have differed in their faith on rebirth. Further, the Islam as well
      as the most dominant religion of the world, Christianity, having its origin in
      the west, have largely denied reincarnation, though some sub-sects still show
      interest in it. Also many mystic and esoteric schools like theosophical society
      have their unique description on rebirth. This article describes reincarnation as
      perceived by various religions and new religious movements as well as some
      research evidence. 

PMID- 23858251
TI  - Indian legal system and mental health.
AB  - Although there was a rich tradition of legal system in Ancient India, the present
      judicial system of the country derives largely from the British system and is
      based on English Common Law, a system of law based on recorded judicial
      precedents. Earlier legislations in respect of mental health were primarily
      concerned with custodial aspects of persons with mental illness and protection of
      the society. Indian laws are also concerned with determination of competency,
      diminished responsibility and/or welfare of the society. United Nations
      Convention for Rights of Persons with Disabilities (UNCRPD) was adopted in 2006,
      which marks a paradigm shift in respect of disabilities (including disability due
      to mental illness) from a social welfare concern to a human right issue. The new
      paradigm is based on presumption of legal capacity, equality and dignity.
      Following ratification of the convention by India in 2008, it became obligatory
      to revise all the disability laws to bring them in harmony with the UNCRPD.
      Therefore, the Mental Health Act - 1987 and Persons with Disability Act - 1995
      are under process of revision and draft bills have been prepared. Human right
      activists groups are pressing for provisions for legal capacity for persons with
      mental illness in absolute terms, whereas the psychiatrists are in favor of
      retaining provisions for involuntary hospitalization in special circumstances. 

PMID- 23858252
TI  - Mind and consciousness in yoga - Vedanta: A comparative analysis with western
      psychological concepts.
AB  - Study of mind and consciousness through established scientific methods is often
      difficult due to the observed-observer dichotomy. Cartesian approach of dualism
      considering the mind and matter as two diverse and unconnected entities has been
      questioned by oriental schools of Yoga and Vedanta as well as the recent quantum
      theories of modern physics. Freudian and Neo-freudian schools based on the
      Cartesian model have been criticized by the humanistic schools which come much
      closer to the vedantic approach of unitariness. A comparative analysis of the two
      approaches is discussed. 

PMID- 23858253
TI  - Religion and mental health.
AB  - In this chapter, the relation between religion and mental health and vice versa
      has been described. From primitive times different religions have different
      beliefs and systems of worshipping. Every religion with their belief system has
      implications on mental health and illness. We described how Hindu system of
      beliefs and rituals may have an effect in causation of various mental illnesses.
      It is also described how religion can help an individual to sustain one's life in
      various domains. The relationship between different religion and symptomatology
      is described. The impact and outcome of religion on mental health have been
      highlighted. 

PMID- 23858254
TI  - Does Guru Granth Sahib describe depression?
AB  - Sikhism is a relatively young religion, with Guru Granth Sahib as its key
      religious text. This text describes emotions in everyday life, such as happiness,
      sadness, anger, hatred, and also more serious mental health issues such as
      depression and psychosis. There are references to the causation of these
      emotional disturbances and also ways to get out of them. We studied both the
      Gurumukhi version and the English translation of the Guru Granth Sahib to
      understand what it had to say about depression, its henomenology, and religious
      prescriptions for recovery. We discuss these descriptions in this paper and
      understand its meaning within the context of clinical depression. Such knowledge
      is important as explicit descriptions about depression and sadness can help
      encourage culturally appropriate assessment and treatment, as well as promote
      public health through education. 

PMID- 23858255
TI  - Judeo-Christian concepts related to psychiatry.
AB  - The behavioral manifestations of psychotic disorders that are attributed to evil
      spirits in the Judeo-Christian scriptures as demonstrated by Jesus Christ have
      been narrated. The descriptions of false beliefs and the perceptual experiences
      that are consistent with the psychiatric terminologies "delusions and
      hallucinations" are briefly discussed. Attempt has been made to analyze the
      patterns of suicidal behaviors, guilt feelings, and, expressions of depressive
      symptoms in the Jewish culture. Of interest is the mass suicide by the Jews in
      the 1st century AD at the Fort Masada, perhaps the first of its kind recorded in
      the history. Noteworthy are alcohol and related mental health problems prevalent
      in the Jewish culture. While highlighting the descriptions of dreams and their
      revelations recorded in the Bible, it is suggested that such concepts about
      dreams might have influenced Sigmund Freud's classical works on dreams. The
      biblical messages and teachings that could be applied for psychotherapy and
      behavior modification strategies have been outlined. The mental concepts of
      Jewish culture and their relevance to Indian culture have also been discussed
      from a cross-cultural perspective. 

PMID- 23858256
TI  - Role of Islam in the management of Psychiatric disorders.
AB  - With the significant growth of the Muslim population all over the world, there
      exists a corresponding increase in the need for mental health services that suit
      this group of patients. Research demonstrates the effectiveness of the
      integration of spirituality and religiosity into psychotherapy and how religious
      beliefs could affect the management plans. This article discusses the impact of
      various beliefs in the Islamic faith on the bio-psychosocial model for the
      management of different psychiatric disorders including focusing on the
      modification of psychotherapeutic techniques as cognitive restructuring. It also
      shows other types of therapies such as music therapy, meditation therapy, and
      aromatherapy. The main emphasis remains to ensure that Muslim psychiatric
      patients get ethical, acceptable, and effective treatment. 

PMID- 23858257
TI  - Sufism and mental health.
AB  - Human experience in, health and disease, always has a spiritual dimension.
      pirituality is accepted as one of the defining determinants of health and it no
      more remains a sole preserve of religion and mysticism. In recent years,
      pirituality has been an area of research in neurosciences and both in the
      nderstanding of psychiatric morbidity and extending therapeutic interventions it
      seems to be full of promises. Sufism has been a prominent spiritual tradition in
      Islam deriving influences from major world religions, such as, Christianity and
      Hinduism and contributing substantially toward spiritual well-being of a large
      number of people within and outside Muslim world. Though Sufism started in early
      days of Islam and had many prominent Sufis, it is in the medieval period it
      achieved great height culminating in many Sufi orders and their major proponents.
      The Sufism aims communion with God through spiritual realization; soul being the
      agency of this communion, and propounding the God to be not only the cause of all
      existence but the only real existence. It may provide a vital link to understand
      the source of religious experience and its impact on mental health. 

PMID- 23858258
TI  - The Islamic prayer (Salah/Namaaz) and yoga togetherness in mental health.
AB  - Religion and its practices have been duly implicated in treating not only
      problems related to medical health, rather, intervening and preventing such
      problems as well. In the present article, the authors have reviewed significance
      of the Islamic prayers (Salah/Namaaz) in healthcare in general and mental health
      in particular. The nature, procedures, practices and the benefits of Salah have
      been comprehensively described and discussed. In addition, an attempt to combine
      yoga and its practices with Salah has been made for intervening and preventing
      the problems of mental health as an expeditious tool. In upshot, the clinicians
      in the field of mental health care have been suggested to incorporate these two
      viewpoints in their intervention program, at least, for the Muslim patients for a
      more desirable outcome. 

PMID- 23858259
TI  - Impact of Mahatma Gandhi's concepts on mental health: Reflections.
AB  - Mahatma Gandhi can be looked upon as one of the greatest visionaries born. His
      life tells us about the varied emotions he went through as a boy and young adult
      during difficult times, and the experiments he did to cope up with these
      problems. It was his perseverance and dedication to an unrelenting pursuit of his
      goal that finally led to his transformation. His concepts like nonviolence,
      satyagraha, brahmcharya and the concepts related to 'Truth' and 'God' can give
      psychological strength and mental resilience to any individual trying to cope up
      with the demands of life. 

PMID- 23858260
TI  - Applications of Gandhian concepts in psychology and allied disciplines.
AB  - The paper highlights the significance of Gandhian concepts in research in
      psychology and its related fields. To illustrate the application of Gandhian
      ideology, a test of non-violence is described here with its psychometric
      properties. Further, two unexplored research issues having a bearing on clinical
      psychology and psychiatry have been delineated. Firstly, a call for addressing
      the mental health problems of non-violent protesters numbering over one billion
      spread all over the world has been made. And secondly, there is a need for
      understanding the neurological basis of non-violent form of behavior, for
      example, the role of oxytocin, to increase the legitimacy of non-violence as
      adaptive behavior. 

PMID- 23858261
TI  - Marriage as a perceived panacea to mental illness in India: Reality check.
AB  - Marriage is a consensual and contractual relationship recognized by law. In
      India, there is a tremendous social and cultural pressure to marry. It is of
      paramount importance to discuss the relationship between marriage and mental
      illness in Indian scenario as marriage is perceived to be a panacea to mental
      illness by many. This review aims to explore whether marriage contributes to
      mental-health problems; whether it has a protective role; what effect it has on
      pre-existing mental illnesses and its outcome in major mental illnesses. 

PMID- 23858262
TI  - Hinduism, marriage and mental illness.
AB  - For Hindus, marriage is a sacrosanct union. It is also an important social
      institution. Marriages in India are between two families, rather two individuals,
      arranged marriages and dowry are customary. The society as well as the Indian
      legislation attempt to protect marriage. Indian society is predominantly
      patriarchal. There are stringent gender roles, with women having a passive role
      and husband an active dominating role. Marriage and motherhood are the primary
      status roles for women. When afflicted mental illness married women are
      discriminated against married men. In the setting of mental illness many of the
      social values take their ugly forms in the form of domestic violence, dowry
      harassment, abuse of dowry law, dowry death, separation, and divorce. Societal
      norms are powerful and often override the legislative provisions in real life
      situations. 

PMID- 23858263
TI  - Indian concepts on sexuality.
AB  - India is a vast country depicting wide social, cultural and sexual variations.
      Indian concept of sexuality has evolved over time and has been immensely
      influenced by various rulers and religions. Indian sexuality is manifested in our
      attire, behavior, recreation, literature, sculptures, scriptures, religion and
      sports. It has influenced the way we perceive our health, disease and device
      remedies for the same. In modern era, with rapid globalization the unique Indian
      sexuality is getting diffused. The time has come to rediscover ourselves in terms
      of sexuality to attain individual freedom and to reinvest our energy to social
      issues related to sexuality. 

PMID- 23858264
TI  - Indian religious concepts on sexuality and marriage.
AB  - Indian religions and cultures are diverse and have always influenced the way
      people live in this part of the world. Religion has been a very dominant
      influence in marriage, choice of marital partner and cohabitation. The present
      paper looks at various religions in India and their influence on sexual attitudes
      and the institution of marriage. Sikhism, Jainism and the Parsi faith with its
      influence on sexuality and marriage are reviewed. Christian values and the role
      they play in shaping sexual notions as well Christian marriage traditions are
      explored. The paper also looks at the influences Islam has had on marriage and
      sexuality and ends with a feminist perspective on women and sexual attitudes
      towards women. 

PMID- 23858265
TI  - Ardhanareeshwara concept: Brain and psychiatry.
AB  - Ardhanareeshvara is a combination of three words "Ardha," "Nari," and "Ishwara"
      means "half," "woman," and "lord," respectively, which when combined means the
      lord whose half is a woman. It is believed that the God is Lord Shiva and the
      woman part is his consort Goddess Parvati or Shakti. The Ardhanareeshvara
      represents a constructive and generative power. Ardhanareeshvara symbolizes male
      and female principles cannot be separated. It conveys the unity of opposites in
      the universe. The male half stands for Purusha and female half is Prakriti.
      Ardhanareeshvara harmonizes the two conflicting ways of life: The spiritual way
      of the ascetic as represented by Shiva, and the materialistic way of the
      householder symbolized by Parvati. It conveys that Shiva and Shakti are one and
      the same. A human being is not a pure unisexual organism. Each human organism
      bears the potentiality of both male and female sex. Neurohormonal mechanisms have
      been found to be greatly influencing the sexual behavior. The modern world has
      come to understand the concept of "Ardhanareeshwara" as it aspires to resolve the
      paradox of opposites into a unity, not by negation, but through positive
      experiences of life. The matching of opposites produces the true rhythm of life. 

PMID- 23858266
TI  - Osho - Insights on sex.
AB  - Sex is a mysterious phenomenon, which has puzzled even great sages. Human beings
      have researched and mastered the biology of sex. But that is not all. Sex needs
      to be understood from the spiritual perspective too. The vision of Osho is an
      enlightening experience in this regard. Out of the thousands of lectures, five
      lectures on sex made Osho most notorious. Born into a Jain family of Madhya
      Pradesh, Rajneesh, who later wanted himself to be called Osho, is a great master.
      He has spoken volumes on a wide range of topics ranging from sex to super
      consciousness. His contributions in the area of sex are based on the principles
      of "Tantra" which has its origin from Buddhism. This article focuses on his life
      and insights on sex, which if understood properly, can be a stepping stone for
      enlightenment. 

PMID- 23858267
TI  - Vajikarana: Treatment of sexual dysfunctions based on Indian concepts.
AB  - Vajikarana or Vrishya chikitsa is a one of eight major specialty of the Ashtanga
      Ayurveda. This subject is concerned with aphrodisiacs, virility and improving
      health of progeny. As per Charak Samhita, by proper use of these formulations,
      one becomes endowed with good physique, potency, strength, and complexion and
      sexually exhilarated and sexually potent. This in turn is helpful in many common
      sexual dysfunctions, including Infertility, Premature Ejaculation and Erectile
      dysfunction. The therapy is preceded by living in strict compliance with the
      directions mentioned in Ayurvedic classics, various methods of body cleansing and
      other non-medicinal strategies like sexual health promoting conduct, behavior and
      diet. Certain individualized herbal and herbo-mineral combinations are
      administered as per the nature of a person according to the Ayurveda. Many
      limitations need to be considered before considering the use of theses therapy
      like lack of scientific studies, possibilities of adulteration in the herbal and
      herbo-mineral combinations available in market and possibilities of unexpected
      side-effects etc., The article calls upon initiating research in this area so
      that claims of ancient Ayurvedic texts could be substantiated and vajikaran
      therapy may be utilized by modern medicine. 

PMID- 23858268
TI  - Indian mental concepts on children and adolescents.
AB  - Ancient Indian mental concepts of children and adolescents are very similar to
      the contemporary modern concepts. The ancient concepts were based on a very
      positive regard for the children's development, education and future
      independence, adult role and contribution to society. Children were wanted and
      considered precious. The children were categorized in to 4 different varnas based
      on their intelligence, abilities, merit and aptitude and educated accordingly,
      away from their home, at Gurukuls. They had universal right to education. Girls
      received attention equal to boys. The boys were expected to earn their
      livelihood, while the girls were expected to be homemakers. Graduation of the
      young person at the end of education and return to home marked the emancipation
      from adolescence. Children's physical and mental health and its disorders were
      given due attention. Aetiology and treatment of physical and mental disorders was
      in accordance with the overall scientific development of those times. 

PMID- 23858269
TI  - Morality and moral development: Traditional Hindu concepts.
AB  - Morality (from the Latin word moralitas that means "manner, character, proper
      behavior") is the differentiation of intentions, decisions, and actions between
      those that are good (or right) and those that are bad (or wrong). It is
      determined by how one's genetic makeup interacts with the environment. The
      development of morality has been a subject of investigation for a number of
      decades, and our understanding of neuro-biological and psychological mechanisms
      has increased manifolds in the last few decades. Development of morality has been
      of particular significance to psychiatric literature because of its significant
      contribution to the development of one's personality and it's aberration in
      various disorders. Cultures that have been just, equal and moral have been widely
      accepted and appreciated. In this review, we shall summarize the modern theories
      of moral development and then look into a part of our past and cultural heritage
      and review the traditional Hindu concepts of morality and their contribution to
      development of one's personality and their relevance in the current times. 

PMID- 23858270
TI  - The Indian concepts of lifestyle and mental health in old age.
AB  - Lifestyle is the perception of a particular person or entire society towards life
      and it is the way people live, think and behave. In Indian lifestyle, principles
      of Karma (action) and dharma (the righteous way to perform the work) are given
      significant value. In India, earlier, the life of an individual was being
      regulated harmoniously according to the stages (Ashrams) of life, i.e.,
      studentship (Brahmcharya); householder (Grihstha); forest dweller (Vanprasth);
      ascetic (Sanyas) and was meant to maintain the discipline, peace and harmony in
      the family and society. However, revolution in the social milieu and political
      scenario changed the patterns of religious beliefs and lifestyle of individuals.
      And thus, the Indian lifestyle got colored with shadows of cults and cultures.
      The lifestyle affects the longevity and health in old age. Lifestyles also have
      role in developing cognitive disorders like Alzheimer's disease (AD). AD found to
      be more common in socially isolated older adults. Deteriorations in health
      (especially mental health) are often the results of faulty lifestyles like
      smoking, alcohol intake, improper diet and lack of exercise as well as an adverse
      psycho-social milieu. Adopting the advocated principles of Indian concepts of
      lifestyle and paying proper attention to mental illnesses of older adults and
      recognizing their problems may preserve mental health in old age. 

PMID- 23858271
TI  - End-of-life care: Indian perspective.
AB  - According to Hinduism, the main religion of India, the end-of-life (EOL) deals
      with good and bad death. The WHO definition of palliative care stresses on
      improving not only the quality of life of patients facing incurable diseases but
      also their families by providing relief from the pain and suffering that includes
      the psychosocial and spiritual needs as well. The Indian Society of Palliative
      Care has been doing a commendable work and appreciable efforts are being done by
      the Kerala model of delivering the EOL care. The spiritual, ethical issues and
      ethical challenges raised when the patients are in terminal phase are also
      reviewed keeping in mind the socio-cultural norms. The Indian Penal Code (IPC)
      has lacunae, which hamper the physicians from taking proper decision in the EOL
      care. Some of the sections like IPC 309 are defunct and need to be changed. The
      Indian Society for Critical Care Medicine has developed a position statement on
      the patient management of the terminally ill patient in the Intensive Care Unit
      (ICU) which states that the society should move from the paternalistic model to
      the share based decision model of the West when deciding the fate of such
      patients. The literature review on the Indian research on palliative care shows
      very little emphatic results and the medical under graduates show illiteracy. To
      strengthen it Medical Council of India has included the palliative care in its
      curriculum by starting a PG course. Literature review revealed that more research
      from Indian perspective should be done in this area. This article studies the
      core issues of developing palliative care in Indian setting keeping in mind the
      ethical, spiritual and legal issues. 

PMID- 23858272
TI  - Indian family systems, collectivistic society and psychotherapy.
AB  - Indian society is collectivistic and promotes social cohesion and
      interdependence. The traditional Indian joint family, which follows the same
      principles of collectivism, has proved itself to be an excellent resource for the
      care of the mentally ill. However, the society is changing with one of the most
      significant alterations being the disintegration of the joint family and the rise
      of nuclear and extended family system. Although even in today's changed scenario,
      the family forms a resource for mental health that the country cannot neglect,
      yet utilization of family in management of mental disorders is minimal. Family
      focused psychotherapeutic interventions might be the right tool for greater
      involvement of families in management of their mentally ill and it may pave the
      path for a deeper community focused treatment in mental disorders. This paper
      elaborates the features of Indian family systems in the light of the Asian
      collectivistic culture that are pertinent in psychotherapy. Authors evaluate the
      scope and effectiveness of family focused psychotherapy for mental disorders in
      India, and debate the issues and concerns faced in the practice of family therapy
      in India. 

PMID- 23858273
TI  - Ayurvedic concepts related to psychotherapy.
AB  - The perfect balance of mind, body and soul is considered as complete health in
      Ayurveda. Ayurveda has its own identity as most ancient and traditional System of
      Medicine in India. Even Ayurveda emphasizes its treatment modalities into three
      parts viz. Satwawajay Chikitsa, Yuktivyapashray and Daivyapashray Chikitsa.
      Sattvavajaya therapy mentioned in Charakasamhita and it used as new concept of
      psychotherapy in Ayurveda. The effectiveness of "traditional mental health
      promoting practices" was identified as health regimens (swasthvrtt), correct
      behavior (sadvrtt), and yoga. Sattvavajaya as psychotherapy, is the mental
      restraint, or a "mind control" as referred by Caraka, is achieved through
      "spiritual knowledge, philosophy, fortitude, remembrance and concentration.
      Ayurvedic psychotherapy would play a dual role: First, as a revival of authentic
      medical culture, the exercise of a practice with an assumed primordial dimension,
      and second as a discovery of authentic subjectivity, the revelation of a self
      with an assumed interior depth. When we integrate the contemporary art of
      psychotherapy with the ancient science of Ayurveda, it becomes a powerful
      combination that is called Psycho Veda. The integration of Psycho and Veda is
      motivated by the complete integration of the immense but fairly contemporary view
      of the mind, emotions and psyche and how this performs in our lives. Integrating
      Psychotherapy and Vedic principles teaches us how to rediscover critical
      knowledge and awareness of the natural forces and rhythms that compliment and
      strengthen our human experience, through the understanding of the psyche and what
      our inner experiences are and also involving practical daily activities with
      thorough attention to our total environment to bring about radical changes in our
      mental outlook and in physical health. 

PMID- 23858274
TI  - The Bhagavad Gita and contemporary psychotherapies.
AB  - The Bhagavad Gita is based on a discourse between Lord Krishna and Arjuna at the
      inception of the Kurukshetra war and elucidates many psychotherapeutic
      principles. In this article, we discuss some of the parallels between the Gita
      and contemporary psychotherapies. We initially discuss similarities between
      psychodynamic theories of drives and psychic structures, and the concept of three
      gunas. Arjuna under duress exhibits elements of distorted thinking. Lord Krishna
      helps remedy this through a process akin to Cognitive Behavioral Therapy (CBT).
      We ascertain the analogies between the principles of Gita and CBT, grief
      emancipation, role transition, self-esteem, and motivation enhancement, as well
      as interpersonal and supportive psychotherapies. We advocate the pragmatic
      application of age old wisdom of the Gita to enhance the efficacy of
      psychotherapeutic interventions for patients from Indian subcontinent and to add
      value to the art of western psychotherapies. 

PMID- 23858275
TI  - Integrative change model in psychotherapy: Perspectives from Indian thought.
AB  - Different psychotherapeutic approaches claim positive changes in patients as a
      result of therapy. Explanations related to the change process led to different
      change models. Some of the change models are experimentally oriented whereas some
      are theoretical. Apart from the core models of behavioral, psychodynamic,
      humanistic, cognitive and spiritually oriented models there are specific models,
      within psychotherapy that explains the change process. Integrative theory of a
      person as depicted in Indian thought provides a common ground for the integration
      of various therapies. Integrative model of change based on Indian thought, with
      specific reference to psychological concepts in Upanishads, Ayurveda, Bhagavad
      Gita and Yoga are presented. Appropriate psychological tools may be developed in
      order to help the clinicians to choose the techniques that match the problem and
      the origin of the dimension. Explorations have to be conducted to develop more
      techniques that are culturally appropriate and clinically useful. Research has to
      be initiated to validate the identified concepts. 

PMID- 23858276
TI  - Early Childhood to Young Adulthood: An Introduction to the Special Issue.
AB  - The identification and understanding of alterable influences on well-being are at
      the nexus of developmental science and social policy. These influences span the
      life course but child, family, and school experiences in the first two decades
      are particularly instrumental to health and well-being. To investigate some of
      these influences, we report data from the Chicago Longitudinal Study. The study
      investigates the life course development of 1,539 children (93% African American
      and 7% Hispanic) who were born in 1979-1980, grew up in the highest-poverty
      neighborhoods in Chicago, and attended early childhood intervention programs
      beginning in preschool. The goals of the study are to determine the effects of
      participation in the Child-Parent Center Program, document patterns of child and
      family well-being over time, and identify child, family, school, and community
      factors that can promote children's well being. We describe major intervention
      findings and summarize the contributions of a variety of personal, family, and
      school experiences in promoting multiple domains of well-being.

PMID- 23858278
TI  - Integrity of the interface between denture base and soft liner: a scanning
      electron microscopic study.
AB  - Aims and objectives of the study was to study the integrity of the interface
      between the denture base and the soft liner when the thickness of the soft liner
      was 0.5, 1.0 and 2.0 mm, and to study the integrity of the soft liner and denture
      base interface as influenced by aging process. 80 rectangular based specimens
      were fabricated using heat cured acrylic resin. The heat cured component of the
      specimen was fabricated from stainless steel template form by compression molding
      technique. Different thickness of silicone soft layer component was added to heat
      cured acrylic resin component of the specimen following the manufacturer's
      instructions to fabricate the group A, group B, group C and group D specimens.
      All the specimens were subjected to the same finishing and polishing procedures.
      The group A specimens was immediately scanned in scanning electron microscope
      after processing. A thermo statically controlled artificial saliva bath designed
      to maintain the temperature between 38 +/- 4 degrees C was used to simulate the
      oral condition and to age the group B, group C and group D specimens for 3 months
      after which they were subjected to scanning under a scanning electron microscope.
      All the aged specimens demonstrated two types of failures namely adhesive which
      occurred along the bond interface between the soft liner and the acrylic resin
      and adhesive and cohesive type of failure which occurred not only at the
      interface but also within the soft liner material itself. When the data was
      subjected to ANOVA, the group A specimens showed statistical significance with
      group B (P = 0.006), group C (P = 0.007) and group D specimens (P = 0.004), the
      level of significance being (P < 0.05). However, there was no statistical
      significance between group B and C (P = 0.98), group C and D specimens (P =
      0.52), group B and D specimens (P = 0.70), the level of significance being (P <
      0.05). Based on the results, statistical analysis of the results and within the
      limitations of this in vitro study the following conclusions can be drawn: The
      thickness of the liner did not show a statistically significant rate of failure
      on the integrity of the interface between the denture base resin and the soft
      liner and aging conditions simulating the clinical environment showed a
      statistically significant rate of failure on the integrity of the interface
      between the denture base resin and the soft liner. 

PMID- 23858277
TI  - An In Vitro Evaluation of the Microleakage under Complete Metal Crowns Using
      Three Adhesive Luting Cements.
AB  - Despite the material advancements and precise laboratory techniques, cement lines
      are inevitable in fixed prosthodontics which leads to increased dependence on the
      integrity of the cement to maintain the marginal seal. The material class of
      luting agent is known to influence microleakage. Studies of cement dissolution
      and disintegration have produced varying results. Hence, this study was done to
      evaluate marginal leakage under complete metal crowns using three adhesive
      cements, two resin cements (one self cure, one dual cure) and a glass ionomer
      cement. Metal crowns were prepared on sixty intact extracted premolars and were
      randomly divided into three groups of twenty each, with each group using a
      different cement for luting. All the samples were then subjected to thermocycling
      and were sectioned using a diamond saw. Reflected Binocular Stereomicroscope at
      100* magnification was used to study the extent of microleakage at both metal
      cement (MC) and tooth cement (TC) interface, at two opposite margins of each
      sectioned specimen. Data was analyzed with a one way analysis of variance. For
      comparison among the groups multiple comparison Bonferroni test was done. Within
      group data was analysed with independent student t test. Between three groups,
      metal crowns cemented with multilink cement showed significantly less
      microleakage at both the interfaces. Glass ionomer cement recorded maximum
      combined microleakage amongst three cements irrespective of the interfaces.
      Within group, glass ionomer and multilink cement showed more microleakage at MC
      interfaces than at TC interface. A complex interaction between variables related
      to dental restoration, luting agent and tooth structure probably influence
      microleakage. In vitro studies must always be followed by in vivo studies before
      definite conclusion can be drawn. 

PMID- 23858279
TI  - "Occlusal plane orientor": an innovative and efficient device for occlusal plane
      orientation.
AB  - Correct occlusal plane orientation is a prerequisite in Prosthodontic
      reconstructive treatment therapy as it helps in achieving esthetics and phonetics
      anteriorly and forms a milling surface posteriorly where tongue and buccinator
      muscle position the food bolus during mastication. Activity of Muscles during
      clenching will be least, when the occlusal plane is made parallel to plane of
      lost natural teeth. Conventionally the ala-tragus line (Camper's plane) is used
      as a guide for assessment of the occlusal plane and fox plane is used to check
      the parallelism between the two. Occlusal plane orientor is a new device
      developed to mark occlusal plane parallel to ala-tragus line on maxillary
      occlusion rim, thereby saving clinician's time and increasing efficiency.
      Additionally, it is a useful tool for occlusal plane orientation in patients with
      facial deformity, absence of an eye or an ear. 

PMID- 23858280
TI  - Comparative measurement of mesiodistal width of six anterior maxillary and
      mandibular teeth in rajasthan population.
AB  - The purpose of the study was to determine the mesiodistal width of six anterior
      teeth for better esthetics and good tooth arrangement in a cross section of
      Rajasthan population. The mesiodistal dimension of central, lateral incisor and
      canine on right and left sides was measured in 250 males and 250 females, these
      readings were used to determine the mean, minimum and maximum
      maxillary/mandibular teeth 'anterior ratio', difference in mesiodistal width,
      combined mean mesiodistal width, the number and percent of similar teeth of
      maxilla and mandible. It was observed from the present study that there is
      variation in mesiodistal width in right and left sides signifying that the
      anterior teeth are not mirror images of one another. Male subjects have greater
      mesiodistal width than female subjects and right side dominates in most of the
      readings indicating that mesiodistal width is greater on right side than on left
      side. Percentage variability and sexual dimorphism are also important findings of
      this study. This study can prove helpful in replacement of artificial teeth of
      prosthesis in this cross section of population. 

PMID- 23858281
TI  - Effects of conventional welding and laser welding on the tensile strength,
      ultimate tensile strength and surface characteristics of two cobalt-chromium
      alloys: a comparative study.
AB  - The purpose of this study was to evaluate the efficacy of laser welding and
      conventional welding on the tensile strength and ultimate tensile strength of the
      cobalt-chromium alloy. Samples were prepared with two commercially available
      cobalt-chromium alloys (Wironium plus and Diadur alloy). The samples were
      sectioned and the broken fragments were joined using Conventional and Laser
      welding techniques. The welded joints were subjected to tensile and ultimate
      tensile strength testing; and scanning electron microscope to evaluate the
      surface characteristics at the welded site. Both on laser welding as well as on
      conventional welding technique, Diadur alloy samples showed lesser values when
      tested for tensile and ultimate tensile strength when compared to Wironium alloy
      samples. Under the scanning electron microscope, the laser welded joints show
      uniform welding and continuous molt pool all over the surface with less porosity
      than the conventionally welded joints. Laser welding is an advantageous method of
      connecting or repairing cast metal prosthetic frameworks. 

PMID- 23858282
TI  - Functional and esthetic rehabilitation of mutilated dentition associated with
      amelogenesis imperfecta.
AB  - This clinical case report describes the oral rehabilitation of an adult female
      patient diagnosed with hypoplastic amelogenesis imperfecta with inadequate,
      deteriorated restorations of anterior teeth, inadequate clinical crown heights of
      posterior teeth due to severe attrition of hypoplastic enamel. Treatment included
      extraction of teeth with poor prognosis, root canal treatment and crown
      lengthening of severely worn out teeth & full coverage porcelain-fused-to metal
      fixed restoration of entire dentition. The main objectives of the selected
      treatment were to enhance the esthetics, restore masticatory function and
      eliminate the teeth sensitivity. These treatment objectives were successfully met
      by sequential fixed prosthodontics treatment using Pankey-Mann-Schuyler
      philosophy of complete occlusal rehabilitation. Treatment not only restored
      function and esthetic, but also showed a positive psychological impact and
      thereby improved perceived quality of life. 

PMID- 23858284
TI  - Prosthetic rehabilitation of a post evisceration patient with custom made ocular
      prosthesis: a case report.
AB  - It is the god given right of human being to appear human, and the face is a
      person's visiting card. We can hide everything but we can't hide our face. Eyes
      are generally the first feature of the face to be noticed and the presence of a
      pair of eyes is quite essential to maintain the balance and the esthetics of the
      face. Loss of eye has a crippling effect on the psychology of the patient. The
      aim of all ocular prosthetic procedure is to enable rehabilitation of the patient
      in the society with a normal appearance and self esteem. This article describes a
      clinical report of rehabilitating post evisceration patient due to glaucoma of
      right eye with custom made artificial prosthesis using stock eye shell that can
      create esthetically pleasing results. 

PMID- 23858283
TI  - Rehabilitation of partial maxillectomy defect with implant retained hollow bulb
      obturator prosthesis: a case report.
AB  - Tissue integrated oral implants have initiated a new perspective in oral
      rehabilitation of tumor patients who have had undergone surgical resection
      procedure. The present case demonstrated a simple and predictable approach to
      rehabilitate a patient who had partial maxillectomy using dental implants. The
      use of an implant in conjunction with hollow bulb obturator shared remarkable
      improvement in retention and stability of the existing complete denture
      prosthesis. 

PMID- 23858285
TI  - Full mouth rehabilitation with maxillary tooth supported and mandibular tooth and
      implant supported combination prostheses: a 4-year case report.
AB  - The primary objectives of successful prosthetic rehabilitation are to provide
      function, esthetics and comfort to the patient. Combination prosthesis is one
      which is supported by both natural teeth and implant. The periodontal ligament
      and osseointegrated interface distribute force differently to the supporting
      bone. Therefore problems can develop when tooth and implants are combined in the
      same prosthesis. However, clinicians can apply biomechanical principles, to
      negate the deleterious leverages exerted by the fixed prosthesis by using non
      rigid components and to equalize the stress applied by the prosthesis on implant
      and teeth. A case of partially edentulous situation was rehabilitated
      successfully with a combination of prostheses. Maxillary arch was restored to
      function with crowns, fixed dental prosthesis and with an extra coronal castable
      attachment prosthesis and the mandibular arch with a combination of tooth and
      implant supported attachment prosthesis. The clinical and laboratory steps for
      the fabrication of these prostheses are explained in this report. 

PMID- 23858286
TI  - Immediate implant placement: a case report.
AB  - This case report describes extraction of a fractured left maxillary lateral
      incisor tooth, followed by immediate placement of a dental implant in the
      prepared socket and temporization by a bonded restoration. The tooth was
      atraumatically extracted, the socket was prepared to the required depth and a
      Biohorizon Implant was inserted followed a week later by temporization by a
      bonded restoration. An impression was made 4 months after implant insertion, and
      a definitive restoration was placed. The atraumatic operating technique and the
      immediate insertion of the Implant resulted in the preservation of the hard and
      soft tissues at the extraction site. The patient exhibited no clinical or
      radiologic complications through 5 years of clinical monitoring. The dental
      implant and provisional restoration provided the patient with immediate
      esthetics, function, comfort, and most importantly preservation of tissues. 

PMID- 23858287
TI  - Designing a custom made gauge device for application in the access hole
      correction in the dental implant surgical guide.
AB  - Anatomic limitation and restorative demands encourage the surgeon to gain
      precision in planning and surgical positioning of dental implants. Ideal
      placement facilitates the establishment of favorable forces on the implants and
      the prosthetic component as well as ensures an esthetic outcome. The
      predictability of success can be increased, if the implants are placed properly.
      During oral implant placement, the drill must be guided by the surgeon according
      to the final form of the restoration. A surgical template would be helpful in
      more accurate placement of the dental implants. Surgical guides fabricated in
      laboratory are still being used. But these guides often need correction after
      computed tomography (CT) scan evaluation. For their correction and reducing the
      possibility of error, a scaled milling machine is usually required. But this
      scaled milling machine is not available omnipresent. In this article a simple
      device is described that can be attached to any milling machine and surveyor. The
      presented device can correct the diagnostic template easily and predicts dental
      implants placement with more favorable esthetic and occlusal outcome. 

PMID- 23858288
TI  - Coracoid bone graft osteolysis after Latarjet procedure: A comparison study
      between two screws standard technique vs mini-plate fixation.
AB  - AIMS: One of the reason for Latarjet procedure failure may be coracoid graft
      osteolysis. In this study, we aimed to understand if a better compression between
      the coracoid process and the glenoid, using a mini-plate fixation during the
      Latarjet procedure, could reduce the amount of coracoid graft osteolysis.
      MATERIALS AND METHODS: A computed tomography scan analysis of 26 prospectively
      followed-up patients was conducted after modified Latarjet procedure using mini
      plate fixation technique to determine both the location and the amount of
      coracoid graft osteolysis in them. We then compared our current results with
      results from that of our previous study without using mini-plate fixation to
      determine if there is any statistical significant difference in terms of
      corcacoid bone graft osteolysis between the two surgical techniques. RESULTS: The
      most relevant osteolysis was represented by the superficial part of the proximal
      coracoid, whereas the deep part of the proximal coracoid graft is least involved
      in osteolysis and has best bone healing. The current study showed a significant
      difference only for the deep part of the distal coracoid with our previous study
      (P < 0.01). DISCUSSION: To our knowledge, there are no studies in literature that
      show the causes of coracoid bone graft osteolysis after Latarjet procedure.
      CONCLUSION: Our study suggests that there is a significant difference only for
      the deep part of the distal coracoid in terms of osteolysis. At clinical
      examination, this difference did not correspond with any clinical findings. LEVEL
      OF EVIDENCE: Level 4. CLINICAL RELEVANCE: Prospective case series, Treatment
      study.

PMID- 23858289
TI  - A biomechanical assessment of superior shoulder translation after reconstruction
      of anterior glenoid bone defects: The Latarjet procedure versus allograft
      reconstruction.
AB  - BACKGROUND: The coracoacromial ligament (CAL) is an important restraint to
      superior shoulder translation. The effect of CAL release on superior stability
      following the Latarjet is unknown; therefore, our purpose was to compare the
      effect of two Latarjet techniques and allograft reconstruction on superior
      instability. MATERIALS AND METHODS: Eight cadaveric specimens were tested on a
      simulator. Superior translation was monitored following an axial force in various
      glenohumeral rotations (neutral, internal, and external) with and without muscle
      loading. Three intact CAL states were tested (intact specimen, 30% glenoid bone
      defect, and allograft reconstruction) and two CAL deficient states (classic
      Latarjet (classicLAT) and congruent-arc Latarjet (congruentLAT)). RESULTS: In
      neutral without muscle loading, a significant increase in superior translation
      occurred with the classicLAT as compared to 30% defect (P = 0.046) and allograft
      conditions (P = 0.041). With muscle loading, the classicLAT (P = 0.005, 0.002)
      and the congruentLAT (P = 0.018, 0.021) had significantly greater superior
      translation compared to intact and allograft, respectively. In internal rotation,
      only loaded tests produced significant results; specifically, classicLAT
      increased translation compared to all intact CAL states (P < 0.05). In external
      rotation, only unloaded tests produced significant results with classicLAT and
      congruentLAT allowing greater translations than intact (P <= 0.028). For all
      simulations, the allograft was not significantly different than intact (P > 0.05)
      and no differences (P = 1.0) were found between classicLAT and congruentLAT.
      DISCUSSION: In most simulations, CAL release with the Latarjet lead to increased
      superior humeral translation. CONCLUSION: The choice of technique for glenoid
      bone loss reconstruction has implications on the magnitude of superior humeral
      translation. This previously unknown effect requires further study to determine
      its clinical and kinematic outcomes.

PMID- 23858290
TI  - Beyond the peak of the anterior glenoid rim: A cadaveric study.
AB  - PURPOSE: The purpose of this study was to quantify the width of bone beyond the
      peak of the anterior glenoid rim and to determine if this anatomic region of the
      glenoid significantly affects measurement of the anteroposterior glenoid
      diameter. MATERIALS AND METHODS: 19 cadaveric scapulae were examined and the
      width of bone beyond the peak of the anterior glenoid rim was measured. The
      percent width of this region relative to the anteroposterior diameter of the
      glenoid was evaluated. Male and female specimens were compared. Measurements of
      the anteroposterior diameter of the glenoid, both including and excluding this
      region, were compared. RESULTS: The mean width of bone beyond the peak of the
      anterior glenoid rim was 3.2 +/- 0.7 mm, corresponding to 10.5% of the
      anteroposterior glenoid diameter. This anatomic region is of similar relative
      size in males and females (11% vs 10% of the glenoid diameter). Measurement of
      the anteroposterior diameter of the glenoid is significantly different depending
      on whether this region is included or not (P = 0.0064). CONCLUSIONS: There exists
      a portion of the anterior glenoid that is beyond the peak of the anterior rim,
      and is not part of the concave articular surface. The width of this anatomic area
      comprises a significant percent of the anteroposterior glenoid diameter, and
      should be understood when quantifying and describing anterior glenoid bone loss
      in cases of glenohumeral instability. CLINICAL RELEVANCE: Understanding of
      anterior glenoid anatomy is important in the evaluation of glenohumeral
      instability. The portion of glenoid bone beyond the anterior rim peak is likely
      important for its soft tissue attachments, but its contribution to bony stability
      may be misunderstood.

PMID- 23858291
TI  - Ossification of the suprascapular ligament: A risk factor for suprascapular nerve
      compression?
AB  - INTRODUCTION: Entrapment of the suprascapular nerve at the suprascapular notch
      may be due to an ossified suprascapular ligament. The present study was conducted
      in order to investigate the incidence of this anomaly and to analyze the
      resultant bony foramen (foramen scapula) for gross nerve compression. MATERIALS
      AND METHODS: We evaluated 104 human scapulae from 52 adult skeletons for the
      presence of complete ossification of the suprascapular ligament. When an ossified
      suprascapular ligament was identified, the diameter of the resultant foramen was
      measured. Also, the suprascapular regions of 50 adult cadavers (100 sides) were
      dissected. When an ossified suprascapular ligament was identified, the spinati
      musculature was evaluated for gross atrophy and the diameters of the resultant
      foramen scapulae and the suprascapular nerve were measured. Immunohistochemical
      analysis of the nerve was also performed. RESULTS: For dry scapular specimens,
      5.7% were found to have an ossified suprascapular ligament. The mean diameter of
      these resultant foramina was 2.6 mm. For cadavers, an ossified suprascapular
      ligament was identified in 5% of sides. Sections of the suprascapular nerve at
      the foramen scapulae ranged from 2 to 2.8 mm in diameter. In all cadaveric
      samples, the suprascapular nerve was grossly compressed (~10-20%) at this site.
      All nerves demonstrated histologic signs of neural degeneration distal to the
      site of compression. The presence of these foramina in male cadavers and on right
      sides was statistically significant. CONCLUSIONS: Based on our study, even in the
      absence of symptoms, gross compression of the suprascapular nerve exists in cases
      of an ossified suprascapular ligament. Asymptomatic patients with an ossified
      suprascapular ligament may warrant additional testing such as electromyography.

PMID- 23858292
TI  - Digital photography for assessment of shoulder range of motion: A novel clinical
      and research tool.
AB  - PURPOSE: Maintenance of a pain-free functional range of motion is the aim of
      surgery for shoulder trauma. The aim of this study was to show that the range of
      motion can be accurately assessed using digital photographs. MATERIALS AND
      METHODS: We reviewed 17 patients who had undergone surgery for shoulder trauma.
      Each patient's range of motion was assessed by two physicians and two
      physiotherapists. Digital photographs were taken of each patient at their
      functional limit. Photographs were assessed by two physicians and two
      physiotherapists, and by an external physician who had no previous contact with
      the patients. RESULTS: Inter-observer and intra-observer reliability trials
      showed excellent correlation of results. There was no significant difference
      between observer's results, or between results of physical examination and
      photographic examination. CONCLUSIONS: Digital photography is a viable adjunct to
      assessment of range of motion of the shoulder. This has positive implications
      both clinically, and for shoulder research. LEVEL OF EVIDENCE: Level 3.

PMID- 23858293
TI  - Supraspinatus and infraspinatus compartment syndrome following scapular fracture.
AB  - Acute compartment syndrome occurs when pressure within a confined fascial space
      rises to a level impairing microvascular perfusion to surrounding
      tissues.[1234567] The majority of the reported literature is based on lower
      extremity compartment syndrome, but any muscle group within an osteofascial
      compartment has the potential to develop compartment syndrome. We report a case
      of a 64-year-old male who developed an acute compartment syndrome of both the
      supraspinatus and infraspinatus after sustaining a severely comminuted scapula
      fracture. Diagnosis of compartment syndrome was made after intracompartmental
      pressure measurements of the supraspinatus and infraspinatus revealed pressures
      within 30 mmHg of the diastolic blood pressure, prompting emergency decompressive
      fasciotomy. At final follow-up, the examination revealed full shoulder strength
      with near-full range of motion. There were no signs of sequelae from compartment
      syndrome at any point. Few case reports describe compartment syndrome of the
      periscapular fascial compartments. However, these cases were either
      retrospectively diagnosed[89] or diagnosed via magnetic resonance imaging (MRI)
      findings and lab values.[910] Surgical management of acute compartment syndrome
      of the supraspinatus has been reported in only one other case.[10] To our
      knowledge, we report the only case of a patient with acute compartment syndrome
      of both the supraspinatus and infraspinatus compartments treated with emergent
      decompressive fasciotomy. Due to the devastating complications and functional
      loss of a missed diagnosis of compartment syndrome, a high index of clinical
      suspicion for developing compartment syndrome must be maintained in every
      fracture setting, regardless of anatomic location or rarity of reported cases. 

PMID- 23858294
TI  - Arthroscopic autograft reconstruction of the inferior glenohumeral ligament:
      Exploration of technical feasibility in cadaveric shoulder specimens.
AB  - Failure of primary arthroscopic Bankart repair in anterior-inferior glenohumeral
      instability is low, but in some cases revision surgery is required. Revision
      procedures show good to excellent results but typically are done open and do not
      respect the anatomical functionality of the joint capsule. The purpose of this
      cadaveric study was to explore the feasibility of a completely arthroscopic
      anatomical reconstruction of the inferior glenohumeral ligament using a hamstring
      autograft. 

PMID- 23858295
TI  - Metal markers for radiographic visualization of rotator cuff margins: A new
      technique for radiographic assessment of cuff repair integrity.
AB  - Surgically repaired rotator cuff repairs may re-tear in the post-operative follow
      up phase, and periodic imaging is useful for early detection. The authors
      describe a simple surgical technique that provides a visible clue to the tendon
      edge on an anteroposterior radiograph of the shoulder. The technique involves
      arthroscopic or mini-open radio-opaque tagging of the tendon edge using a metal
      marker, and followed by a double-row rotator cuff repair using suture anchors.
      Serial post-operative radiographs may then be used to monitor the position of the
      marker. Progressive or marked displacement of the marker suggests a failure of
      cuff repair integrity and should be evaluated further. 

PMID- 23858296
TI  - Digitoxin induces apoptosis in cancer cells by inhibiting nuclear factor of
      activated T-cells-driven c-MYC expression.
AB  - BACKGROUND: Cardiac glycosides such as digitoxin have been shown to directly
      cause apoptotic death of cancer cells both in vitro, and in vivo. However, the
      mechanism connecting cardiac glycoside action to apoptosis is not known. It has
      been reported that compounds resembling digitoxin are able to reduce c-MYC
      expression. Furthermore, it has been previously shown that the transcription of c
      MYC depends on nuclear factor of activated T-cells (NFAT) binding sites in the c
      MYC promoter. We have therefore hypothesized that NFAT might mediate digitoxin
      effects on c-MYC mRNA message. MATERIALS AND METHODS: We have chosen to study
      this process in HeLa cells where structurally intact c-MYC genes in 8q24 co
      localize with human papilloma virus 18 at all integration sites. RESULTS: Here we
      show that within the 1(st) h following treatment with digitoxin, a significant
      reduction in c-MYC mRNA occurs. This is followed by a precipitous loss of c-MYC
      protein, activation of caspase 3, and subsequent apoptotic cell death. To test
      the NFAT-dependence mechanism, we analyzed the effects of digitoxin on NFAT
      isoform-dependent auto-activation of a NFAT-luciferase expression system. Drug
      dependent effects on expression varied according to each of the four canonical
      NFAT isoforms (1, 2, 3 or 4). The most digitoxin-sensitive NFAT isoform was
      NFAT1. Using c-MYC chromatin immune precipitation, we find that digitoxin
      inhibits interaction of NFAT1 with the proximal c-MYC promoter. CONCLUSIONS:
      These results suggest that the carcinotoxic activity of digitoxin includes
      suppression of NFAT-driven c-MYC expression.

PMID- 23858297
TI  - Applications of metabolomics in cancer research.
AB  - The first discovery of metabolic changes in cancer occurred almost a century ago.
      While the genetic underpinnings of cancer have dominated its study since then,
      altered metabolism has recently been acknowledged as a key hallmark of cancer and
      metabolism-focused research has received renewed attention. The emerging field of
      metabolomics - which attempts to profile all metabolites within a cell or
      biological system - is now being used to analyze cancer metabolism on a system
      wide scale, painting a broad picture of the altered pathways and their
      interactions with each other. While a large fraction of cancer metabolomics
      research is focused on finding diagnostic biomarkers, metabolomics is also being
      used to obtain more fundamental mechanistic insight into cancer and
      carcinogenesis. Applications of metabolomics are also emerging in areas such as
      tumor staging and assessment of treatment efficacy. This review summarizes
      contributions that metabolomics has made in cancer research and presents the
      current challenges and potential future directions within the field. 

PMID- 23858298
TI  - Stage-specific analysis of plasma protein profiles in ovarian cancer: Difference
      in-gel electrophoresis analysis of pooled clinical samples.
AB  - INTRODUCTION: Ovarian cancer is the leading cause of death from gynecological
      cancer. Non-specific symptoms early in disease and the lack of specific
      biomarkers hinder early diagnosis. Multi-marker blood screening tests have shown
      promise for improving identification of early stage disease; however, available
      tests lack sensitivity, and specificity. MATERIALS AND METHODS: In this study,
      pooled deeply-depleted plasma from women with Stage 1, 2 or 3 ovarian cancer and
      healthy controls were used to compare the 2-dimensional gel electrophoresis (2
      DE) protein profiles and identify potential novel markers of ovarian cancer
      progression. RESULTS/DISCUSSION: Stage-specific variation in biomarker expression
      was observed. For example, apolipoprotein A1 expression is relatively low in
      control and Stage 1, but shows a substantial increase in Stage 2 and 3, thus,
      potential of utility for disease confirmation rather than early detection. A
      better marker for early stage disease was tropomyosin 4 (TPM4). The expression of
      TPM4 increased by 2-fold in Stage 2 before returning to "normal" levels in Stage
      3 disease. Multiple isoforms were also identified for some proteins and in some
      cases, displayed stage-specific expression. An interesting example was fibrinogen
      alpha, for which 8 isoforms were identified. Four displayed a moderate increase
      at Stage 1 and a substantial increase for Stages 2 and 3 while the other 4 showed
      only moderate increases. CONCLUSION: Herein is provided an improved summary of
      blood protein profiles for women with ovarian cancer stratified by stage.

PMID- 23858299
TI  - Effects of maternal dietary exposure to cadmium during pregnancy on mammary
      cancer risk among female offspring.
AB  - BACKGROUND: Since heavy metal cadmium is an endocrine disrupting chemical, we
      investigated whether maternal exposure to cadmium during the pregnancy alters
      mammary tumorigenesis among female offspring. METHODS: From gestation day 10 to
      day 19, pregnant rat dams were fed modified American Institute of Nutrition
      (AIN93G) diet containing 39% energy from fat (baseline diet), or the baseline
      diet containing moderate (75 MUg/kg of feed) or high (150 MUg/kg) cadmium levels.
      Some dams were injected with 10 MUg 17beta-estradiol (E2) daily between gestation
      days 10 and 19. RESULTS: Rats exposed to a moderate cadmium dose in utero were
      heavier and exhibited accelerated puberty onset. Both moderate and high cadmium
      dose led to increased circulating testosterone levels and reduced the expression
      of androgen receptor in the mammary gland. The moderate cadmium dose mimicked the
      effects of in utero E2 exposure on mammary gland morphology and increased both
      the number of terminal end buds and pre-malignant hyperplastic alveolar nodules
      (HANs), but in contrast to the E2, it did not increase 7, 12-dimethylbenz (a)
      anthracene-induced mammary tumorigenesis. CONCLUSIONS: The effects of in utero
      cadmium exposure were dependent on the dose given to pregnant dams: Moderate, but
      not high, cadmium dose mimicked some of the effects seen in the in utero E2
      exposed rats, such as increased HANs in the mammary gland.

PMID- 23858300
TI  - Validation of a digital photographic method for assessment of dietary quality of
      school lunch sandwiches brought from home.
AB  - BACKGROUND: It is a challenge to assess children's dietary intake. The digital
      photographic method (DPM) may be an objective method that can overcome some of
      these challenges. OBJECTIVE: The aim of this study was to evaluate the validity
      and reliability of a DPM to assess the quality of dietary intake from school
      lunch sandwiches brought from home among children aged 7-13 years. DESIGN: School
      lunch sandwiches (n=191) were prepared to represent randomly selected school
      lunch sandwiches from a large database. All components were weighed to provide an
      objective measure of the composition. The lunches were photographed using a
      standardised DPM. From the digital images, the dietary components were estimated
      by a trained image analyst using weights or household measures and the dietary
      quality was assessed using a validated Meal Index of Dietary Quality (Meal IQ).
      The dietary components and the Meal IQ obtained from the digital images were
      validated against the objective weighed foods of the school lunch sandwiches. To
      determine interrater reliability, the digital images were evaluated by a second
      image analyst. RESULTS: Correlation coefficients between the DPM and the weighed
      foods ranged from 0.89 to 0.97. The proportion of meals classified in the same or
      an adjacent quartile ranged from 98% (starch) to 100% (fruits, vegetables, fish,
      whole grain, and Meal IQ). There was no statistical difference between fish, fat,
      starch, whole grains, and Meal IQ using the two methods. Differences were found
      for fruits and vegetables; Bland-Altman analyses showed a tendency to
      underestimate high amounts of these variables using the DPM. For interrater
      reliability, kappa statistics ranged from 0.59 to 0.82 across the dietary
      components and Meal IQ. CONCLUSIONS: The standardised DPM is a valid and reliable
      method for assessing the dietary quality of school lunch sandwiches brought from
      home.

PMID- 23858302
TI  - From the Editor-in-Chief.

PMID- 23858301
TI  - Health effects of different dietary iron intakes: a systematic literature review
      for the 5th Nordic Nutrition Recommendations.
AB  - BACKGROUND: The present literature review is part of the NNR5 project with the
      aim of reviewing and updating the scientific basis of the 4th edition of the
      Nordic Nutrition Recommendations (NNR) issued in 2004. OBJECTIVE: The objective
      of this systematic literature review was to assess the health effects of
      different intakes of iron, at different life stages (infants, children,
      adolescents, adults, elderly, and during pregnancy and lactation), in order to
      estimate the requirement for adequate growth, development, and maintenance of
      health. METHODS: The initial literature search resulted in 1,076 abstracts. Out
      of those, 276 papers were identified as potentially relevant. Of those, 49 were
      considered relevant and were quality assessed (A, B, or C). An additional search
      on iron and diabetes yielded six articles that were quality assessed. Thus, a
      total of 55 articles were evaluated. The grade of evidence was classified as
      convincing (grade 1), probable (grade 2), suggestive (grade 3), and inconclusive
      (grade 4). RESULTS: There is suggestive evidence that prevention or treatment of
      iron deficiency (ID) and iron deficiency anemia (IDA) improves cognitive,
      motoric, and behavioral development in young children, and that treatment of IDA
      improves attention and concentration in school children and adult women. There is
      insufficient evidence to show negative health effects of iron intakes in doses
      suggested by the NNR 4. There is insufficient evidence to suggest that normal
      birth weight, healthy, exclusively breast-fed infants need additional dietary
      iron before 6 months of life in the Nordic countries. An iron concentration of 4
      8 mg/L in infant formulas seems to be safe and effective for normal birth weight
      infants. There is probable evidence that iron supplements (1-2 mg/kg/day) given
      up to 6 months of age to infants with low birth weight (<2,500 g) prevents IDA
      and possibly reduce the risk of behavioral problems later on. There is probable
      evidence that ID and IDA in pregnant women can be effectively prevented by iron
      supplementation at a dose of 40 mg/day from week 18-20 of gestation. There is
      probable evidence that a high intake of heme iron, but not total dietary, non
      heme or supplemental iron, is associated with increased risk of type 2 diabetes
      (T2D) and gestational diabetes. CONCLUSIONS: Overall, the evidence does not
      support a change of the iron intakes recommended in the NNR 4. However, one could
      consider adding recommendations for infants below 6 months of age, low birth
      weight infants and pregnant women.

PMID- 23858303
TI  - Skeletal muscle: an endocrine organ.
AB  - Tropism and efficiency of skeletal muscle depend on the complex balance between
      anabolic and catabolic factors. This balance gradually deteriorates with aging,
      leading to an age-related decline in muscle quantity and quality, called
      sarcopenia: this condition plays a central role in physical and functional
      impairment in late life. The knowledge of the mechanisms that induce sarcopenia
      and the ability to prevent or counteract them, therefore, can greatly contribute
      to the prevention of disability and probably also mortality in the elderly. It is
      well known that skeletal muscle is the target of numerous hormones, but only in
      recent years studies have shown a role of skeletal muscle as a secretory organ of
      cytokines and other peptides, denominated myokines (IL6, IL8, IL15, Brain-derived
      neurotrophic factor, and leukaemia inhibitory factor), which have autocrine,
      paracrine, or endocrine actions and are deeply involved in inflammatory
      processes. Physical inactivity promotes an unbalance between these substances
      towards a pro-inflammatory status, thus favoring the vicious circle of
      sarcopenia, accumulation of fat - especially visceral - and development of
      cardiovascular diseases, type 2 diabetes mellitus, cancer, dementia and
      depression, according to what has been called "the diseasome of physical
      inactivity". 

PMID- 23858304
TI  - Early diagnosis of vertebral fractures.
AB  - Vertebral fractures are a common clinical entity, caused by trauma or related to
      osteoporosis (benign). Their recognition is especially important in the post
      menopausal female population but also important is their differentiation from
      pathological (malignant) fractures (1). A vertebral fracture is evidenced by
      vertebral body deformity or reduction in vertebral body height beyond a certain
      threshold value in the absence of bone discontinuity. For prognosis and treatment
      it is extremely important to recognize the cause of the fracture. In contrast to
      fractures that occur in other locations, vertebral fractures often go
      unrecognized in the acute phase as the pain may be transient and radiographic and
      evaluation of the spine may be difficult (2). Objective measurement of the
      vertebral deformity provides invaluable information to the interpreting physician
      and helps grade fracture severity. The recognition and diagnosis of vertebral
      fractures can be performed using additional diagnostic tools. 

PMID- 23858305
TI  - The genetic profile of bone repair.
AB  - Bone repair following a fracture is a complex, well orchestrated, physiological
      process in response to injury. Even though the exact number of the genes and
      expressed proteins involved in fracture healing remains unknown, the molecular
      complexity of the repair process has been demonstrated, and it involves numerous
      genes and molecules, such as extracellular matrix genes, growth and
      differentiation factors, matrix metalloproteinases, angiogenic factors and
      others. Discrepancies in fracture healing responses and final outcome seen in the
      clinical practice may be attributed among other factors to biological variations
      between patients and different genetic "profiles", resulting in "altered"
      signalling pathways that regulate the bone repair process. Preliminary human
      studies support a "genetic" component in the pathophysiology of impaired bone
      repair seen in atrophic non-unions by correlating genetic variations of specific
      molecules regulating fracture healing with non-union. However, the role of the
      genetic "profile" of each individual in fracture healing and final outcome, and
      its possible interaction with other exogenous factors remains a topic of
      extensive research. 

PMID- 23858306
TI  - Tissue engineering applications in the management of bone loss.
AB  - Several conditions in Orthopaedics and Traumatology are characterized by a bone
      loss. Bone auto- or allo-grafting was considered sufficient to fullfill the
      defects decades ago; however, large bone defects were challenging for the
      Surgeons, particularly in case of necessity of structural and biological
      properties. Bioindusrty proposed over the years synthetic biomaterials, as
      Demineralized Bone Matrix, bioactive surfaces for implant coponents, and recently
      recombinant Bone Morphogenetic Proteins. At the same time, the concept of the
      "biological chamber" and "diamond concept" allowed the scientific community to
      consider the need of a more complex interaction between scaffolds (matrix), cells
      (mesenchymal cells), and signaling (growth factors) in order to induce bone
      regeneration and also to fill small or large bone defects. A brief overview is
      made on the processes of a physiologic bone metabolism (induction, conduction,
      osteogenesis), on the latest therapeutical procedures, based on the use of
      autologous growth factors and cells, and the recent prosthetic or synthetic
      scaffolds, and the common clinical conditions that may beneficiate of these
      modern approaches. 

PMID- 23858307
TI  - Growth factors in the treatment of early osteoarthritis.
AB  - Regenerative medicine is the science that studies the regeneration of biological
      tissues obtained through use of cells, with the aid of support structures and
      with biomolecules such as growth factors. As regards the growth factors the PRP,
      or the platelet-rich plasma, obtained from a withdrawal of autologous blood,
      concentrating the platelets, represents a safe, economical, easy to prepare and
      easy to apply source of growth factors. Numerous growth factors are in fact
      within the platelets and in particular a large number of them have a specific
      activity on neo-proliferation, on cartilage regeneration and in particular also
      an antiapoptotic effect on chondroblasts: - The PDGF which regulates the
      secretion and synthesis of collagen;- The EGF that causes cellular proliferation,
      endothelial chemotaxis and angiogenesis;- The VEGF that increases angiogenesis
      and vascular permeability;- The TGF-beta that stimulates the proliferation of
      undifferentiated MSC, stimulates chemotaxis of endothelial cells and
      angiogenesis;- The bFGF that promotes the growth and differentiation of
      chondrocytes and osteoblasts stimulates mitogenesis of mesenchymal cells,
      chondrocytes and osteoblasts. These properties have led to the development of
      studies that evaluated the efficacy of treatment of infiltrations in the knee and
      hip with platelet-derived growth factors. Regarding the knee it was demonstrated
      that in patients with moderate degree of gonarthrosis, the PRP is able to
      significantly reduce the pain and improve joint function, both on placebo and
      towards infiltrations with hyaluronic acid. The success of the treatment was
      proportional to the age of and inversely proportional to the severity of
      osteoarthritis according to Kellgren and Lawrence classification. The possibility
      of infiltrations guided with ultrasound into the hip led us to extend the
      indications also to hip arthrosis, as already showed by Sanchez. Even in
      coxarthrosis preliminary results at 6 and 12 months show that a cycle of 3
      infiltrations of PRP has significantly decreased the pain and increased range of
      motion and joint function. 

PMID- 23858308
TI  - Atypical femoral fractures.
AB  - Bisphosphonates (BPs) represent the most widely used therapy for osteoporosis.
      Recently, a relationship between long-term treatment with BPs and a subset of
      atypical femoral fractures (AFFs) from below the lesser trochanter to the
      sovracondilar line has been described. Many etiopathogenetic theories have been
      invoked to explain AFFs: reduced bone turnover and increased osteoblast bone
      apposition with accumulation of microdamage and decreased bone toughness with
      subsequent increased risk of micro-cracks and duration fractures, collagen fiber
      cross-linking and vascularization impairment. Based on published studies, a task
      force of the American Society for Bone and Mineral Research has redacted the
      diagnostic criteria of AFFs by classifying them according to their major and
      minor criteria. The treatment for displaced AFFs is osteosynthesis, but there is
      a lack of evidence for undisplaced AFFs and the duration of fracture treatment.
      BPs have a proven efficacy in osteoporotic fracture reduction as well as in the
      treatment of other bone diseases caused by the downregulation of osteoclast
      activity. BPs have an excellent benefit-to-risk ratio; however, minor adverse
      events, such as AFFs, occur in a variable percentage of patients treated over a
      long period of time. 

PMID- 23858309
TI  - The effects on bone cells of metal ions released from orthopaedic implants. A
      review.
AB  - The increasing use of orthopedic implants and, in particular, of hip and knee
      joint replacements for young and active patients, has stimulated interest and
      concern regarding the chronic, long-term effects of the materials used. This
      review focuses on the current knowledge of the adverse biologic reactions to
      metal particles released from orthopaedic implants in vivo and in vitro. More
      specifically, the purpose of this article is to provide an overview of the
      current literature about the adverse effects of metal particles on bone cells and
      peri-implant bone. 

PMID- 23858310
TI  - Hip arthrosis and surgical intervention: what and when?
AB  - Osteoarthritis of the hip is a common pathology and involves forms of disability
      and need for treatments that affect the quality of life of patients and their
      families, and in general of the whole society. It should be considered as such
      degenerative joint disease is increasing as the increase in life expectancy and
      musculoskeletal trauma, the latter responsible for secondary forms of
      osteoarthritis. The treatment of osteoarthritis of the hip has changed a lot over
      the years, since the earlier diagnosis and, before, with prevention through
      proper lifestyle. More in-depth knowledge of the biology of the tissues involved,
      first of all hyaline cartilage, has lead to non-surgical treatments such as
      infiltration with hyaluronic acid (viscosupplementation) and autologous growth
      factors derived from platelets (platelet rich plasma). Surgical therapy with
      prosthetic replacement is finally a choice to share with the patient based on
      pain and functional limitation, bearing in mind always the best technology and
      tribology and the possibility of less invasive surgical access, while recognizing
      that there are not still eternal prosthesis. Of particular importance then is the
      age of the patient. There are also other types of surgery (hip arthroscopy,
      forage) for other pathologies of the hip which can be resolutive, or, in a sense,
      can delay the arrival to the prosthetic replacement. We will discuss below the
      decision-making process that leads the surgeon with the patient to the surgery
      option. 

PMID- 23858311
TI  - The contribution of cortical and trabecular tissues to bone strength: insights
      from denosumab studies.
AB  - All materials undergo an aging process which is characterized essentially by
      changes of the rigidity (stiffness), of the ability to absorb the stresses
      (toughness) and then ultimately in the mechanical resistance (strength). Both
      cortical and trabecular bone undergo a continuous process of structural
      remodeling with the main aim to preserve their biomechanical properties. An
      imbalance in this process, which promotes bone resorption, results in a
      quantitative loss of bone tissue and in a qualitative alteration of the skeletal
      microarchitecture, as you can see in osteoporosis, rheumatoid arthritis or bone
      metastases. Cortical component has a prominent role on strength therefore loss of
      cortical bone that is prevalent in elderly may explain the higher frequency of
      fractures of bones composed mainly of cortical bone such as the proximal femur.
      Remodeling inhibition with denosumab improved structural strength without
      altering material properties, that can be primarily explained by the combined
      effects of increased trabecular and cortical bone mass, and reductions in
      trabecular eroded surfaces and particularly cortical porosity. Denosumab for its
      mechanism of action and pharmacokinetics results in a significant, early and
      continued increase in BMD with enhanced bone strength improving both cortical and
      trabecular bone. 

PMID- 23858312
TI  - Clinical and surgical approach of severe bone fragility fracture: clinical case
      of 4 fragility fracture in patient with heavy osteoporosis.
AB  - An accurate diagnosis of osteoporosis and a proper treatment are today recognized
      to be the most important facts for prevention and for a correct arrangement and
      treatment of fragility fractures. In the text the Authors describe a case of
      severe osteoporosis aggravated by 2 femur fractures and 2 periprosthetic
      fractures occurred in 2 months. In such cases the orthopaedic surgeon needs to
      formulate first a clinical osteoporotic pattern, than its treatment together with
      a surgery suitable choice, that has to take into consideration of the bone
      structural characteristics. In the case described one can note that fractures
      healing occurred thanks to both an improvement in surgical techniques and
      antiosteoporotic pharmacological support; in the specific case the Authors used
      strontium ranelate for its osteoinductive capacity. In our opinion is crucial
      that the treatment used by orthopaedic surgeons is not related only to the "by
      hand" treatment but take into consideration both the underlying disease and the
      possibility of positively affect bone healing with specific drug therapy. 

PMID- 23858313
TI  - Evaluation of persistence and adherence to teriparatide treatment in patients
      affected by severe osteoporosis (PATT): a multicenter observational real life
      study.
AB  - INTRODUCTION: Osteoporosis is a chronic condition leading to an increased risk of
      developing fractures, with high morbidity and mortality in aging population.
      Efficacy of anti-osteoporotic treatment is based on drug potency but also on
      compliance and persistence to treatment regimen, which is very low, as already
      described for other diseases. Teriparatide (TPTD) is the first anabolic agent
      developed for the treatment of osteoporosis. Since it appears that persistence to
      Teriparatide declines over time, aim of this pilot multicenter observational
      study was to evaluate persistence and adherence to TPTD (20 MUg daily injection
      regimen for 18 months) treatment (PATT) in patients affected by severe
      osteoporosis in an every day clinical practice. METHODS: Patients affected by
      severe osteoporosis were selected among those who referred to 5 different
      specialized centers for osteoporosis in North, Center and South of Italy. A
      sample of 475 women with severe postmenopausal osteoporosis treated with TPTD in
      accordance to the Italian osteoporosis guidelines was included. At the beginning
      of TPTD treatment patients were instructed on the use of the device by the
      referring specialist of the center, a resident fellow or a nurse. Bone
      biochemical markers were evaluated the same morning and after 1, 3, 6, 12 and 18
      months. Patients were visited at time 0 and after 6, 12 and 18 months for
      clinical follow up. RESULTS: The results included observations of 441/475
      patients (98% women) who completed the 18 months treatment; mean age for women
      was 73+/-8 and for men 65+/-9. After 6 months of TPTD treatment persistence was
      of 89,79%, 87,75% after 12 months and 86,85% after 18 months. Adherence was of
      100% at 6,12 and 18 months. Total dropouts were 13,15% (71/441), which was
      usually higher within the first 6 months of TPTD treatment. Most common adverse
      events (arthralgies 2,7%, dizziness 1,8%, migraine 1,8%, depression 1,6%,
      hypertension 1,1%) were reported in 62/441 patients (14%) of patients, but were
      not reason for stopping treatment. CONCLUSIONS: The persistence and adherence to
      TPTD treatment obtained in this multicenter observational real life study was
      very high as compared to studies performed by others. These encouraging results
      suggest that different key factors such quality of information, frequency of
      visits, motivations given to patients, opportunity to call the doctor might play
      a pivotal role in the high persistence and adherence to TPTD treatment obtained
      in our study and need to be carefully considered before prescribing chronic anti
      osteoporotic therapy.

PMID- 23858314
TI  - Bisphosphonate treatment for osteolysis in total hip arthroplasty. A report of
      four cases.
AB  - Aseptic loosening due to wear debris is the most frequent modality of failure in
      total hip arthroplasty. Bisphosphonates, a class of molecules which inhibit bone
      resorption showed an inhibitory effects on particles-induced osteolysis in vitro
      and in animal models. We report the clinical, radiographic and densitometric
      outcome of four postmenopausal women with total hip arthroplasty affected by peri
      prosthetic osteolysis treated with neridronate due to their unwillingness to be
      operated. After neridronate treatment, there was general improvement in pain and
      function: VAS decrease 13 points (15%), the Harris Hip Score increase 9 points
      (15%). An average number of 3.3 x-ray per patients with an average follow-up of
      23 months (range 12-34) were collected and evaluated. In all the patients except
      one, serial radiographs didn't show any progression of radioluciencies lines or
      periprosthetic osteolysis. Bone density was evaluated by Dual energy X-ray
      absorptiometry after an average follow-up of 21 months (range 6-46 mo):
      periprosthetic BMD around the whole stem and the cup increased respectively 2.4%
      and 7.1%. Treatment was well tolerated and no significant side effects were
      registered. This retrospective collection of a small group of patients suggest
      that bisphosphonates should be clinically useful in preventing periprosthetic
      wear debris mediated osteolysis and claim for dedicated clinical trials. 

PMID- 23858315
TI  - Hyperparathyroidism-jaw tumour syndrome detected by aggressive generalized
      osteitis fibrosa cystica.
AB  - Severe hyperparathyroidism can affect bone metabolism and be in the origine of
      multiple brown tumours (generalized osteitis fibrosa cystica). When associated
      with fibro-ossifying tumours of the jaw, it realizes a rare genetic syndrome
      referred as Hyperparathyroidism-jaw tumour HPT-JT. We report the case of a
      patient we treated for HPT-JT, and literature review. 

PMID- 23858316
TI  - Science as ground of the Renaissance artists.

PMID- 23858318
TI  - Cytomorphology of Boerhaave's syndrome: A critical value in cytology.
AB  - Spontaneous esophageal perforation into the pleural cavity (Boerhaave's syndrome)
      is a rare life-threatening condition, which requires early diagnosis and urgent
      management. The diagnosis of such critical condition in many cases is delayed
      because of atypical clinical presentation, resulting in increased morbidity and
      mortality. Cytological examination of pleural fluid can provide early, fast and
      accurate diagnosis of such critical condition and help in better and early
      management of this disease. We describe a case of an 81-year-old female with
      esophageal perforation who presented with a left sided pleural effusion. The
      correct diagnosis was established in this case by observing gastrointestinal-like
      fluid characteristics of the thoracic drainage upon cytological and chemical
      analyses and the rupture was confirmed by esophagography. The cytological
      examination of pleural fluid revealed benign reactive squamous cells, fungal
      organisms, bacterial colonies, and vegetable material consistent with a ruptured
      esophagus. Cytological examination of pleural fluid is a rapid and accurate
      technique that can help in establishing the diagnosis of this challenging entity
      and guide initiation proper management of this unusual entity. 

PMID- 23858317
TI  - Abdominopelvic washings: A comprehensive review.
AB  - Intraperitoneal spread may occur with gynecological epithelial neoplasms, as well
      as with non-gynecological malignancies, which may result in serosal involvement
      with or without concomitant effusion. Therefore, washings in patients with
      abdominopelvic tumors represent important specimens for cytologic examination.
      They are primarily utilized for staging ovarian cancers, although their role has
      decreased in staging of endometrial and cervical carcinoma. Abdominopelvic
      washings can be positive in a variety of pathologic conditions, including benign
      conditions, borderline neoplastic tumors, locally invasive tumors, or distant
      metastases. In a subset of cases, washings can be diagnostically challenging due
      to the presence of co-existing benign cells (e.g., mesothelial hyperplasia,
      endosalpingiosis, or endometriosis), lesions in which there is only minimal
      atypia (e.g., serous borderline tumors) or scant atypical cells, and the rarity
      of specific tumor types (e.g., mesothelioma). Ancillary studies including
      immunocytochemistry and fluorescence in situ hybridization may be required in
      difficult cases to resolve the diagnosis. This article provides a comprehensive
      and contemporary review of abdominopelvic washings in the evaluation of
      gynecologic and non-gynecologic tumors, including primary peritoneal and
      mesothelial entities. 

PMID- 23858319
TI  - Metastatic colorectal adenocarcinoma in cervicovaginal cytology specimens
      confirmed by immunocytochemical stains on liquid base specimens: Two study cases
      with review of the literature.
AB  - Only a few cases of adenocarcinoma (ACA) metastatic to the female lower genital
      tract diagnosed on cervicovaginal Pap smear have been reported during the past
      several decades. Both conventional and liquid based cytology (LBC) have limited
      sensitivity and specificity in diagnosing metastatic disease and
      immunocytochemical (ICC) staining may be needed for confirming the diagnosis. We
      present two cases of metastatic colorectal ACA diagnosed on cervicovaginal
      ThinPrep (TP) Pap smears, with one confirmed by ICC staining method. Recognition
      of extra-uterine malignancy in the cervicovaginal cytology specimen is critical
      for the disease diagnosis, prognosis, and the treatment. ICC staining performed
      on the residual LBC specimen is an important methodology to confirm the
      diagnosis. 

PMID- 23858320
TI  - Performance of endoscopic ultrasound-guided fine needle aspiration in diagnosing
      pancreatic neuroendocrine tumors.
AB  - BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are rare tumors of the
      pancreas, which are increasingly diagnosed by endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA). In this retrospective study, we assessed the
      performance of EUS-FNA in diagnosing PNETs. MATERIALS AND METHODS: We identified
      48 cases of surgically resected PNETs in which pre-operative EUS-FNA was
      performed. The clinical features, cytological diagnoses, and surgical follow-up
      were retrospectively reviewed. The diagnostic performance of EUS-FNA was analyzed
      as compared to the diagnosis in the follow-up. The cases with discrepancies
      between cytological diagnosis and surgical follow-up were analyzed and diagnostic
      pitfalls in discrepant cases were discussed. RESULTS: The patients were 20 male
      and 28 female with ages ranging from 15 years to 81 years (mean 57 years). The
      tumors were solid and cystic in 41 and 7 cases, respectively, with sizes ranging
      from 0.5 cm to 11 cm (mean 2.7 cm). Based on cytomorphologic features and adjunct
      immunocytochemistry results, when performed, 38 patients (79%) were diagnosed
      with PNET, while a diagnosis of suspicious for PNET or a diagnosis of neoplasm
      with differential diagnosis including PNET was rendered in the 3 patients (6%).
      One case was diagnosed as mucinous cystic neoplasm (2%). The remaining 6 patients
      (13%) had non-diagnostic, negative or atypical diagnosis. CONCLUSIONS: Our data
      demonstrated that EUS-FNA has a relatively high sensitivity for diagnosing PNETs.
      Lack of additional materials for immunocytochemical studies could lead to a less
      definite diagnosis. Non-diagnostic or false negative FNA diagnosis can be seen in
      a limited number of cases, especially in those small sized tumors.

PMID- 23858321
TI  - Cytodiagnosis of gouty tophus.

PMID- 23858322
TI  - Gallbladder carcinoma: An attempt of WHO histological classification on fine
      needle aspiration material.
AB  - BACKGROUND: Carcinoma of the gallbladder (CaGB) is common in India and its
      prognosis depends primarily on the extent of the disease and histological type.
      We aim to study the role of guided fine needle aspiration cytology (FNAC) for
      diagnosis of CaGB and to evaluate the feasibility of applying world health
      organization (WHO) classification on fine needle aspiration (FNA) material to
      predict the outcome of the tumor. MATERIALS AND METHODS: Retrospective
      cytomorphologic analysis was performed in all cases of CaGB diagnosed by
      ultrasound (US) guided FNAC over a period of 2 years. A specific subtype was
      assigned according to WHO classification based on characteristic cytologic
      features. These included papillary or acinar arrangement, intra and extracellular
      mucin, keratin, rosettes and columnar, signet ring, atypical squamous, small,
      clear, spindle and giant cells. Correlation with histopathology was performed
      when available. RESULTS: A total of 541 aspirations with clinical or radiological
      suspicion of primary CaGB were studied. Of these, 54 aspirates were
      unsatisfactory. Fifty cases were negative for malignancy. Remaining 437 aspirates
      were positive for carcinoma. Histopathologic diagnosis was available in 32 cases.
      Adenocarcinoma was the most frequent diagnosis in 86.7% of cases. Mucinous,
      signet ring, adenosquamous, squamous, small cell, mixed adenoneuroendocrine and
      undifferentiated carcinoma including spindle and giant cell subtypes were
      diagnosed identifying specific features on FNAC. Correlation with histopathology
      was present in all, but one case giving rise to sensitivity of 96.8%. No post-FNA
      complications were recorded. CONCLUSIONS: US guided FNAC is a safe and effective
      method to diagnose CaGB. Although, rare, clinically and prognostically
      significant variants described in WHO classification can be detected on cytology.

PMID- 23858323
TI  - Cytopathology of neoplastic meningitis: A series of 66 cases from a tertiary care
      center.
AB  - BACKGROUND: Neoplastic meningitis (NM) is a condition characterized by
      leptomeningeal involvement by metastatic carcinoma. Detection of exfoliated
      malignant cells in cerebrospinal fluid (CSF) due to meningeal metastasis is
      frequently associated with diverse neurologic presentations. MATERIALS AND
      METHODS: In this retrospective study of all cases of NM diagnosed in CSF samples
      over a 20-year period at a tertiary care referral center, the cytomorphologic
      features were reviewed. RESULTS: Sixty six cases of NM were identified of which
      36 already had an established diagnosis of malignancy while in 30 patients, there
      was no previously known tumor. The most common known primary in the former group
      was breast followed by ovary. Single cell pattern, cellular cannibalism, moderate
      cytoplasm and rounded nuclei were seen in breast and lung tumors. Papillary
      architecture and cytoplasmic vacuolation were seen in the ovarian primaries.
      Melanin pigment was seen in malignant melanoma. CONCLUSION: CSF cytology is an
      important tool for diagnosis of NM. Cytomorphologic features helped in diagnosis
      and for prediction of the primary site. Correct identification of this condition
      is important as it has therapeutic and prognostic implications.

PMID- 23858324
TI  - Retraction: Primary extraosseous Ewing sarcoma of the lung in children.
AB  - ecancer 7 312 (2013) The report in this article of the treatment the patient
      received is incorrect. Three of the authors (Jean Luc Michel, Clara Fernandez and
      Audrey Derouet) were unaware that their names had been added to the author list.
      The three remaining authors (Nidal Alsit, Linda Sakhri and Augustin Pirvu) were
      not involved with the treatment of the patient. 

PMID- 23858326
TI  - The balance and gait disorder of essential tremor: what does this mean for
      patients?
AB  - Essential tremor (ET), once considered a monosymptomatic disease, is now viewed
      as a syndrome characterized by action tremor as well as a variety of other
      neurological features. These features include deficits of both balance (i.e. the
      ability to maintain the body within its base of support) and gait. Balance and
      gait abnormalities in ET have been studied most extensively in the laboratory,
      with the disability and burden on life, as experienced by patients with ET, being
      a subject of relatively less scrutiny. In this paper, we review the data on
      balance and gait impairment in ET. These include data both from objective
      assessments (bedside examination or laboratory gait analysis) and subjective
      assessments (patients' reports of imbalance). We discuss the clinical
      implications of the current data, and suggest a tiered approach to begin to
      address the still unanswered questions in this field. This tiered approach starts
      with an attempt to isolate a subpopulation of patients who are at greatest risk
      of difficulty with balance and gait, and then later focuses on this subgroup to
      assess the burden of any balance and gait impairments as well as the impact of
      potential therapeutic interventions. 

PMID- 23858325
TI  - Topiramate: Effects on cognition in patients with epilepsy, migraine headache and
      obesity.
AB  - This paper reviews the clinical implications of topiramate (TPM)-induced
      cognitive deficits in patients with epilepsy, migraine headache, obesity, and in
      normal populations, followed by reviews of the literature describing the reversal
      of such deficits upon medication discontinuation. It also discusses animal
      investigations of TPM's role of neuroprotection in brain injury. TPM's most
      intolerable adverse effects (AEs) are on verbal fluency and reaction time,
      resulting in high discontinuation rates in patients taking it for epilepsy and
      migraine headache. However, because TPM is so effective in the treatment of
      epilepsy and migraine headache, its use is expected to continue. There appears to
      be greater tolerance of TPM's cognitive AEs when it is used in the treatment of
      obesity, perhaps because of the lower doses required. Research attempting to
      predict the populations most vulnerable to the cognitive effects caused by TPM is
      ongoing. Studies suggest that one such population may include patients with a
      past psychiatric history. Slow titration and administration of the lowest
      possible doses may decrease risk of cognitive deficits. 

PMID- 23858327
TI  - Sex and gender issues in multiple sclerosis.
AB  - Multiple sclerosis (MS) is universally found to be more prevalent in women than
      men. This has led to extensive studies of differences in the immune system or
      nervous system between women and men, which might be caused by the effects of
      gonadal hormones, genetic differences, and different environmental exposures and
      modern lifestyle in men and women. We review the effects of sex and gender from a
      genetic, immunological and clinical point of view. We discuss the effects of sex
      on the clinical expression of MS and responses to therapy, as well as issues
      concerning pregnancy. 

PMID- 23858329
TI  - Initiating oral fingolimod treatment in patients with multiple sclerosis.
AB  - Fingolimod, the first oral disease-modifying therapy (DMT) approved for the
      treatment of multiple sclerosis (MS) and the only sphingosine 1-phosphate
      receptor modulator approved for any disease state, represents an important
      addition to the expanding DMT options for patients with MS. In three large phase
      III clinical trials, fingolimod 0.5 mg reduced relapses by approximately half
      compared with either placebo or weekly intramuscular interferon beta1a. The risks
      associated with the use of fingolimod include first-dose bradycardia, macular
      edema, and elevation of liver enzymes; fingolimod may increase the risk of
      infections, some serious in nature, and potentially cause fetal harm.
      Breakthrough disease or intolerance of injectable medications may be factors that
      influence the initiation of fingolimod. Identification of potential patients
      suitable for fingolimod treatment requires a thorough understanding of the
      potential risks and the particular fingolimod indication of the national
      authority. To minimize risk, recommended baseline assessments that should be made
      prior to fingolimod initiation include complete blood count, liver transaminase
      levels, total bilirubin levels, electrocardiogram (ECG), ophthalmologic
      examination, varicella zoster infection status, and for women, childbearing
      potential. First-dose observation is required for all patients for at least 6 h,
      with hourly pulse and blood pressure measurements and ECG before and 6 h after
      the first dose. In the European Union, continuous telemetry monitoring is
      recommended. Healthcare providers should be aware of the potential for
      symptomatic bradycardia and the need for continuous overnight ECG monitoring for
      those at higher risk for bradycardia. With experience in over 63,000 patients and
      over 73,000 patient-years of exposure in clinical trials and postmarketing use,
      the benefits and full safety profile of fingolimod continue to become better
      elucidated. This information will enable healthcare providers to initiate
      fingolimod in appropriately selected and screened patients with MS. 

PMID- 23858328
TI  - Neuroradiological evaluation of demyelinating disease.
AB  - Central nervous system inflammatory demyelinating disease can affect patients
      across the life span. Consensus definitions and criteria of all of the different
      acquired demyelinating diseases that fall on this spectrum have magnetic
      resonance imaging criteria. The advances of both neuroimaging techniques and
      important discoveries in immunology have produced an improved understanding of
      these conditions and classification. Neuroimaging plays a central role in the
      accurate diagnosis, prognosis, disease monitoring and research efforts that are
      being undertaken in this disease. This review focuses on the imaging spectrum of
      acquired demyelinating disease. 

PMID- 23858330
TI  - Cervical cancer in pregnant women: treat, wait or interrupt? Assessment of
      current clinical guidelines, innovations and controversies.
AB  - Cervical cancer during pregnancy is relatively uncommon. However, the incidence
      is expected to increase as more women delay childbearing. When preservation of
      the pregnancy is desired, optimal treatment is a major challenge to all. Whereas
      delay of treatment is an option for pre-invasive disease, and also small invasive
      carcinomas without lymph node involvement, management of tumours >2 cm remains
      experimental. Type of treatment needs to be individualized and depends mainly on
      gestational age, disease stage, and histology. Extensive counselling regarding
      the maternal and foetal risks is required. In this current review, we aim to
      summarize available data and treatment guidelines concerning cervical cancer in
      pregnancy. Controversies and research priorities are also identified. 

PMID- 23858331
TI  - What is the optimal neo-adjuvant treatment for liver metastasis?
AB  - Colorectal cancer is the third most common cancer in the Western population and
      has a 5-year overall survival of 5-10% when metastatic. Approximately 30% of the
      patients with metastatic colorectal cancer have limited disease apparently
      isolated to the liver and, if this can be resected, the 5-year overall survival
      is improved to 30-60%. Therefore, it is important to identify patients who have
      both resectable disease and those with initially unresectable tumors who can
      potentially be downsized with chemotherapy to allow resection. First-line doublet
      chemotherapy regimens lead to response rates of 50-60%, triplet chemotherapy
      regimens may result in a response rate of up to 70%, and biological agents may
      add to responses or induce morphologic changes that facilitate disease resection.
      Surgical advances in recent years have also increased resectability rates and
      have challenged prior rules of resectability. Local therapies including ablation
      and radiation, often performed in conjunction with resection, may further aid in
      control of disease. The aim of this article is to focus on the role of
      neoadjuvant therapy in the treatment of colorectal liver metastases. 

PMID- 23858332
TI  - Detection and minimally invasive treatment of early squamous lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the most common cause of cancer deaths
      worldwide. The majority of patents presenting with NSCLC have advanced disease,
      which precludes curative treatment. Early detection and treatment might result in
      the identification of more patients with early central lung cancer and improve
      survival. In addition, the study of early lung cancer improves understanding of
      lung carcinogenesis and might also reveal new treatment targets for advanced lung
      cancer. Bronchoscopic investigation of the central airways can reveal both early
      central lung cancer in situ (stage 0) and other preinvasive lesions such as
      dysplasia. In the current review we discuss the detection of early squamous lung
      cancer, the natural history of preinvasive lesions and whether biomarkers can be
      used to predict progression to cancer. Finally we will review the staging and
      management of preinvasive lung cancer lesions and the different therapeutic
      modalities that are available. 

PMID- 23858334
TI  - Bisphosphonate drug holiday: who, when and how long.
AB  - Bisphosphonates have been widely used in the treatment of osteoporosis with
      robust data from numerous placebo-controlled trials demonstrating efficacy in
      fracture risk reduction over 3-5 years of treatment. Although bisphosphonates are
      generally safe and well tolerated, concerns have emerged about adverse effects
      related to long-term use. For most patients with osteoporosis, the benefits of
      treatment outweigh the risks. Because these agents accumulate in bone with some
      persistent antifracture efficacy after therapy is stopped, it is reasonable to
      consider a 'drug holiday.' There is considerable controversy regarding the
      optimal duration of therapy and the length of the holiday, both of which should
      be based on individual assessments of risk and benefit. 

PMID- 23858335
TI  - Milnacipran combined with pregabalin in fibromyalgia: a randomized, open-label
      study evaluating the safety and efficacy of adding milnacipran in patients with
      incomplete response to pregabalin.
AB  - OBJECTIVE: To evaluate the safety, tolerability, and efficacy of adding
      milnacipran to pregabalin in patients with fibromyalgia who have experienced an
      incomplete response to pregabalin. METHODS: In this randomized, multicenter, open
      label study, patients received pregabalin 300 or 450 mg/day during a 4- to 12
      week run-in period. Patients with weekly recall visual analog scale (VAS) pain
      score of at least 40 and up to 90, Patient Global Impression of Severity score of
      at least 4, and Patient Global Impression of Change (PGIC) score of at least 3
      were classified as incomplete responders and randomized to continue pregabalin
      alone (n = 180) or receive milnacipran 100 mg/day added to pregabalin (n = 184).
      The primary efficacy parameter was responder status based on PGIC score of up to
      2. The secondary efficacy parameter was change from randomization in weekly
      recall VAS pain score. Safety parameters included adverse events (AEs), vital
      signs, and clinical laboratory tests. RESULTS: The percentage of PGIC responders
      was significantly higher with milnacipran added to pregabalin (46.4%) than with
      pregabalin alone (20.8%; p < 0.001). Mean improvement from randomization in
      weekly recall VAS pain scores was greater in patients receiving milnacipran added
      to pregabalin (-20.77) than in patients receiving pregabalin alone (-6.43; p <
      0.001). During the run-in period, the most common treatment-emergent AEs with
      pregabalin were dizziness (22.8%), somnolence (17.3%), and fatigue (9.1%). During
      the randomized period, the most common treatment-emergent AEs with milnacipran
      added to pregabalin were nausea (12.5%), fatigue (10.3%), and constipation
      (9.8%). CONCLUSIONS: In this exploratory, open-label study, adding milnacipran to
      pregabalin improved global status, pain, and other symptoms in patients with
      fibromyalgia with an incomplete response to pregabalin treatment.

PMID- 23858333
TI  - Targeted therapies in non-small cell lung carcinoma: what have we achieved so
      far?
AB  - The search for innovative therapeutic agents in non-small cell lung cancer
      (NSCLC) has witnessed a swift evolution. The number of targeted drugs that can
      improve patient outcomes with an acceptable safety profile is steadily
      increasing. In this review, we highlight current drugs that have already been
      approved or are under evaluation for the treatment of patients with NSCLC, either
      in monotherapy or combined therapy for both the first- and second-line settings.
      Experience with drugs targeting the vascular endothelial growth factor and its
      receptor, as well as the epidermal growth factor receptor is summarized.
      Moreover, we provide an overview of more novel targets in NSCLC and initial
      experience with the respective therapeutic agents. 

PMID- 23858336
TI  - A review on strontium ranelate long-term antifracture efficacy in the treatment
      of postmenopausal osteoporosis.
AB  - Osteoporotic fractures are one of the major causes of increased morbidity and
      mortality in postmenopausal women and the overall aging population. One of the
      major issues in the management of postmenopausal osteoporosis is to find a safe
      and effective treatment in the long term (>3 years) to achieve and maintain a
      reduction in the risk of fracture. Strontium ranelate (PROTELOS((r))) is a
      relatively novel drug, currently approved in Europe for the treatment of
      postmenopausal osteoporosis. Strontium ranelate is the first agent of a new
      therapeutic class in osteoporosis, capable of both promoting bone formation and,
      to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover
      results in a net gain in bone mineral density (BMD), bone quality improvement and
      reduction in risk of vertebral and nonvertebral fractures, as initially
      demonstrated in the preplanned long-term registrative trials SOTI (Spinal
      Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral
      Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS
      trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of
      strontium ranelate in increasing BMD, the long-term safety profile and the high
      compliance to treatment, independently from baseline BMD or other risk factors
      for osteoporotic fractures. Recent economic impact analyses have proved that long
      term treatment with strontium ranelate is highly cost effective, especially in
      women older than 70 years of age. Histomorphometric analyses in animals and
      humans participating in the phase III trials have proved that the quality of
      mineralization is preserved in the long term and bone microarchitecture is
      ameliorated, with increased bone strength. Thus, strontium ranelate has been
      confirmed to be an effective compound for the long-term, chronic treatment of
      postmenopausal osteoporosis. 

PMID- 23858337
TI  - Targeting interleukin-17 in patients with active rheumatoid arthritis: rationale
      and clinical potential.
AB  - Clinical and experimental evidence suggest that interleukin-17A (IL-17A; also
      known as IL-17) is an attractive therapeutic target in rheumatoid arthritis (RA).
      Rheumatoid synovial tissue produces IL-17A, which causes cartilage and bone
      degradation in synovial and bone explants. Overexpression of IL-17A induces
      synovial inflammation and joint destruction in animal RA models. These effects
      are attenuated in IL-17A-deficient animals and by agents that block IL-17A. Serum
      IL-17A levels and, to a greater extent, synovial fluid IL-17A levels are elevated
      in many patients with RA. In some RA cohorts, higher IL-17A levels have been
      associated with a more severe clinical course. Several IL-17A blockers, including
      the anti-IL-17A monoclonal antibodies secukinumab and ixekizumab, and the anti-IL
      17 receptor subunit A monoclonal antibody brodalumab have been evaluated in phase
      II clinical trials. Of these, secukinumab is the most advanced with respect to
      clinical evaluation in RA, with phase III trials ongoing in patients on
      background methotrexate who had inadequate responses to previous tumor necrosis
      factor blocker therapy. 

PMID- 23858338
TI  - Old World cutaneous leishmaniasis: diagnosis and treatment.
AB  - Cutaneous leishmaniasis is a major world health problem. Diagnosis is suspected
      on evocative clinical presentation in patients living in or coming from endemic
      areas. Several methods have been used. The smear is a simple investigation used
      in endemic regions. The culture enables to identify the specimen. PCR has a high
      sensitivity. Montenegro's reaction is used in the epidemiological study.
      Pentavalent antimony derivatives remain the mainstay of systemic treatment. Their
      efficiency is well established. Their toxicity should be researched. Other
      treatments can be utilized, such as miltefosine. Local therapy is used in
      uncomplicated lesions. Injections of the pentavalent antimony derivate,
      cryotherapy and paromomycin ointmentsis are important options and should be used
      more frequently in Old World leishmaniasis. 

PMID- 23858340
TI  - A Filipino male with encephalocraniocutaneous lipomatosis (Haberland's syndrome).
AB  - BACKGROUND: Encephalocraniocutaneous lipomatosis (ECCL), also known as
      Haberland's Syndrome, is a sporadically occurring neurocutaneous syndrome with no
      gender or race predilection. ECCL patients present with a broad spectrum of
      clinical manifestations, often in a unilateral distribution. The hallmark of ECCL
      is the nevus psiloliparus, a soft, bulging, lipomatous scalp lesion, with
      associated alopecia. MAIN OBSERVATIONS: We describe a case of a 2-month-old
      Filipino male with a soft, ill-defined mass with associated alopecia on the
      fronto-parietal scalp. Biopsy revealed findings consistent with a nevus
      psiloliparus. The patient also presented with a lipomatous nodule on the right
      temple, as well as choristomas and a coloboma on the right eye. He had no history
      of seizures and development was at par with age. CONCLUSION: Recognition of ECCL
      is important in order to work-up the patient for concomitant problems, such as
      central nervous system and cardiac anomalies, and employ a multidisciplinary
      approach in the management of these patients.

PMID- 23858339
TI  - Olmsted syndrome.
AB  - BACKGROUND: Olmsted syndrome is a rare keratinization disorder characterized by a
      combination of periorificial keratotic plaques and bilateral palmoplantar
      transgredient keratoderma. Other clinical manifestations include diffuse
      alopecia, leukokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic
      linear streaks, follicular hyperkeratosis and constriction of digits. MAIN
      OBSERVATIONS: We report a case of Olmsted syndrome in a 5-year-old male presented
      by mutilating palmoplantar keratoderma, perioral keratoses and linear
      hyperkeratotic lower limb plaques. CONCLUSIONS: Olmsted syndrome is a rare
      genodermatosis with only 43 cases reported so far. We present another case of the
      disease.

PMID- 23858341
TI  - Angora hair nevus. A further case of an unusual epidermal nevus representing a
      hallmark of angora hair nevus syndrome.
AB  - BACKGROUND: The association of Blaschko lines with genetic mosaicism has lead to
      the concept that this pattern represents the manifestation of genetically
      abnormal skin tissue contrasting with the genetically normal skin. Various mosaic
      defects affecting not only the skin but also extracutaneous tissues have lead to
      the description of different types of epidermal nevus syndromes. We present a
      further case of an unusual organoid epidermal nevus characterized by depigmented
      hypertrichosis. MAIN OBSERVATIONS: We describe a 2-year-old boy with a
      systematized angora hair nevus being characterized by bands covered with soft
      white hair arranged along Blaschko's lines, involving the scalp, face, and trunk.
      A biopsy obtained from a scalp lesion showed mild epidermal acanthosis and
      increased pigmentation of the basal layer. Trichoscopy the affected scalp hair
      demonstrated fine light coloured shafts. The boy had slight macrocephaly and body
      asymmetry, a sacral pit, and koilonychia of the big toes. CONCLUSIONS: The angora
      hair nevus is a peculiar type of organoid epidermal nevus, representing the
      cutaneous hallmark of a distinctive syndrome, the angora hair nevus syndrome
      (Schauder syndrome). In cases of epidermal nevi showing hypertrichosis, this
      unusual entity should be borne in mind for differential diagnosis.

PMID- 23858342
TI  - Disseminated Nocardia infection presenting as hemorrhagic pustules and ecthyma in
      a woman with systemic lupus erythematosus and antiphospholipid antibody syndrome.
AB  - BACKGROUND: Nocardia is an opportunistic pathogen that can cause disseminated
      infection in immunocompromised hosts. The most common type of skin lesion
      reported with disseminated Nocardia is a subcutaneous nodule; however, there are
      reports with unusual cutaneous presentations. Long term corticosteroid treatment
      is one of the largest risk factors for developing disseminated Nocardia. Initial
      treatment is empiric as each strain has unique susceptibilities and it takes
      weeks to speciate and test sensitivities. MAIN OBSERVATIONS: A 66-year-old female
      on long term corticosteroids for systemic lupus erythematosus (SLE) and
      antiphospholipid syndrome presented with a polymorphous skin eruption and
      systemic symptoms concerning for infection. Especially concerning were areas of
      hemorrhagic pustules on the lower legs, and two ecthymatous lesions on the thigh.
      Tissue culture Gram stain revealed Gram positive branching filamentous rods
      concerning for Nocardia. The patient improved with empiric treatment.
      CONCLUSIONS: This case of Nocardiosis had unusual cutaneous findings that could
      have misguided the clinician, but the tissue culture and Gram stain proved to be
      useful for rapid diagnosis and proper treatment.

PMID- 23858343
TI  - An unusual presentation of giant pilomatrixoma in an adult patient.
AB  - BACKGROUND: Pilomatrixoma (OMIM ID #132600) is a benign cutaneous tumor
      originating from the pilosebaceous follicle and characterized by the presence of
      subcutaneous nodules of up to 3.0 cm in diameter, usually on the head, neck and
      upper extremities. It is most common in the first two decades of life and after
      the age of 60. MAIN OBSERVATIONS: An adult female patient was evaluated,
      presenting a solid tumoral lesion with erythematous surface and purplish tone,
      with approximately 7.5 x 5.0 cm in size, in the interscapulovertebral region. It
      was thought to be an epidermoid cyst, sarcoma, calcified hemangioma, giant
      dermatofibroma, or nodular basal cell carcinoma. The resection of the lesion was
      carried out and, at the histological examination, specific details were observed
      that led to the diagnosis of pilomatrixoma. CONCLUSION: Pilomatrixoma should be
      suspected in the differential diagnosis of giant adnexal tumors.

PMID- 23858344
TI  - Eruptive seborrheic keratoses associated with adalimumab use.
AB  - BACKGROUND: Seborrheic keratoses are common, benign cutaneous growths, however in
      rare situations they can acutely erupt in large numbers. Eruptive seborrheic
      keratoses can be associated with internal malignancy (sign of Leser-Trelat), but
      may also appear in conjunction with inflammatory dermatoses and adverse drug
      reactions. MAIN OBSERVATION: A 71-year-old Caucasian man presented with acute
      onset of a pruritic, burning papular erythematous rash on his chest, upper
      extremities and lower extremities after a routine adalimumab injection for
      rheumatoid arthritis. Two skin biopsies obtained showed findings diagnostic of
      seborrheic keratoses. Spontaneous resolution of the diffuse eruptive seborrheic
      keratoses was achieved within 3 months of discontinuing adalimumab therapy.
      CONCLUSIONS: We believe the development of eruptive seborrheic keratoses due to
      adalimumab therapy is rare, and because our patient responded promptly to
      discontinuation of the drug we suggest this should be the preferred course of
      action in future cases.

PMID- 23858345
TI  - Pyoderma gangrenosum of the breast treated with intravenous immunoglobulin.
AB  - BACKGROUND: Pyoderma gangrenosum is a rare neutrophilic dermatosis which leads to
      necrotic and painful skin ulceration. PG of the breast is extremely rare with 32
      documented cases in the current literature. Delay in diagnosis worsens scarring
      as the ulcers are rapidly expanding, painful and usually slow to heal. CASE
      PRESENTATION: We present a case of pyoderma gangrenosum of the breast in a
      patient with associated rheumatoid arthritis which was initially diagnosed as an
      infected breast ulcer and later successfully treated with systemic steroids and
      intravenous immunoglobulin (IVIG). CONCLUSION: Even though PG of the breast has
      been gaining increased recognition over the past two decades, this has been more
      common in the post-surgical setting. This case highlights the need to consider PG
      as a differential diagnosis when faced with unsual cases of breast ulceration and
      the importance of multidisplinary approach for effective treatment of this
      condition.

PMID- 23858347
TI  - Photoletter to the editor - Nevus lipomatosus superficialis (Hoffmann-Zurhelle).
      Three new cases including one with ulceration and one with ipsilateral gluteal
      hypertrophy.
AB  - Nevus lipomatosis superficialis is a rare, asymptomatic hamartoma of skin. We
      report 3 adult patients with NLS of Hoffmann - Zurhelle type, 2 males and a
      female. Two cases showed clinical peculiarities - ulceration or association with
      ipsilateral gluteal hypertrophy. Reduction buttock lift was performed to improve
      body contour. In conclusion, nevus lipomatosis superficialis can become
      symptomatic. Although simple surgical excision leads to a complete cure in the
      majority of cases, sometimes more complex procedures become necessary. 

PMID- 23858346
TI  - Photoletter to the editor - Calciphylaxis: a diagnostic and therapeutic
      challenge.
AB  - Calciphylaxis is an uncommon necrotizing dermal condition, most often related to
      end-stage renal disease, associated with secondary hyperparathyroidism. The
      incidence is 1-4% per year in dialyzed patients. The condition is characterized
      by microcalcification of small and medium-sized blood vessels, causing cutaneous
      and soft tissue necrosis. The etiology of calciphylaxis is poorly understood,
      although many reports highlight the abnormal calcium-phosphate products as an
      important etiological factor. Calciphylaxis is associated with significant
      morbidity and mortality with estimated 5-year survival rates of less than 50%.
      Sepsis is the main cause of death. We report two patients of calciphylaxis
      treated with surgical debridement and excellent outcome in both cases. 

PMID- 23858348
TI  - JMBE Supports 20 Years of Teaching Excellence at ASMCUE and Offers ASM Laboratory
      Safety Guidelines.

PMID- 23858349
TI  - Oxford-style debates in a microbiology course for majors: a method for delivering
      content and engaging critical thinking skills.
AB  - Developing scientific expertise in the classroom involves promoting higher-order
      cognitive skills as well as content mastery. Effective use of constructivism can
      facilitate these outcomes. However this is often difficult to accomplish when
      delivery of content is paramount. Utilizing many of the tenets of constructivist
      pedagogy, we have designed an Oxford-style debate assignment to be used in an
      introductory microbiology course. Two teams of students were assigned a debatable
      topic within microbiology. Over a five-week period students completed an
      informative web page consisting of three parts: background on the topic, data
      based positions for each side of the argument, and a data-based persuasive
      argument to support their assigned position. This was followed by an in-class
      presentation and debate. Analysis of student performance on knowledge-based
      questions shows that students retain debate-derived content acquired primarily
      outside of lectures significantly better than content delivered during a normal
      lecture. Importantly, students who performed poorly on the lecture-derived
      questions did as well on debate-derived questions as other students. Students
      also performed well on questions requiring higher-order cognitive skills and in
      synthesizing data-driven arguments in support of a position during the debate.
      Student perceptions of their knowledge-base in areas covered by the debate and
      their skills in using scientific databases and analyzing primary literature
      showed a significant increase in pre- and postassignment comparisons. Our data
      demonstrate that an Oxford-style debate can be used effectively to deliver
      relevant content, increase higher-order cognitive skills, and increase self
      efficacy in science-specific skills, all contributing to developing expertise in
      the field. 

PMID- 23858350
TI  - How much is too much assessment? Insight into assessment-driven student learning
      gains in large-scale undergraduate microbiology courses.
AB  - Designing and implementing assessment tasks in large-scale undergraduate science
      courses is a labor-intensive process subject to increasing scrutiny from students
      and quality assurance authorities alike. Recent pedagogical research has provided
      conceptual frameworks for teaching introductory undergraduate microbiology, but
      has yet to define best-practice assessment guidelines. This study assessed the
      applicability of Biggs' theory of constructive alignment in designing consistent
      learning objectives, activities, and assessment items that aligned with the
      American Society for Microbiology's concept-based microbiology curriculum in
      MICR2000, an introductory microbiology course offered at the University of
      Queensland, Australia. By improving the internal consistency in assessment
      criteria and increasing the number of assessment items explicitly aligned to the
      course learning objectives, the teaching team was able to efficiently provide
      adequate feedback on numerous assessment tasks throughout the semester, which
      contributed to improved student performance and learning gains. When comparing
      the constructively aligned 2011 offering of MICR2000 with its 2010 counterpart,
      students obtained higher marks in both coursework assignments and examinations as
      the semester progressed. Students also valued the additional feedback provided,
      as student rankings for course feedback provision increased in 2011 and
      assessment and feedback was identified as a key strength of MICR2000. By
      designing MICR2000 using constructive alignment and iterative assessment tasks
      that followed a common set of learning outcomes, the teaching team was able to
      effectively deliver detailed and timely feedback in a large introductory
      microbiology course. This study serves as a case study for how constructive
      alignment can be integrated into modern teaching practices for large-scale
      courses. 

PMID- 23858351
TI  - Engaging Students in Authentic Microbiology Research in an Introductory Biology
      Laboratory Course is Correlated with Gains in Student Understanding of the Nature
      of Authentic Research and Critical Thinking.
AB  - Recent recommendations for biology education highlight the role of authentic
      research experiences early in undergraduate education as a means of increasing
      the number and quality of biology majors. These experiences will inform students
      on the nature of science, increase their confidence in doing science, as well as
      foster critical thinking skills, an area that has been lacking despite it being
      one of the desired outcomes at undergraduate institutions and with future
      employers. With these things in mind, we have developed an introductory biology
      laboratory course where students design and execute an authentic microbiology
      research project. Students in this course are assimilated into the community of
      researchers by engaging in scholarly activities such as participating in inquiry,
      reading scientific literature, and communicating findings in written and oral
      formats. After three iterations of a semester-long laboratory course, we found
      that students who took the course showed a significant increase in their
      understanding of the nature of authentic research and their level of critical
      thinking skills. 

PMID- 23858352
TI  - PILOTing Undergraduate Students to Hands-On Teaching and Research Skills.
AB  - Undergraduate research can make a positive impact on science education.
      Unfortunately, the one student-one mentor paradigm of undergraduate research
      generates a wide range of variability in the student's experience and further
      limits its availability to a select few students. In contrast, a single faculty
      member can offer multiple undergraduate teaching positions that provide a
      consistent experience for the student. We attempted to combine the undergraduate
      research and teaching experiences in an internship practicum called Peer
      Instruction and Laboratory Occupational Training (PILOT). Students enrolled in
      PILOT served as teaching assistants for the upper division Quantitative
      Biological Methods (QBM) laboratory course. In addition, PILOT students worked on
      an independent lab project that provided them with hands-on training and
      supported the QBM course. The development of presentation and teaching skills was
      also emphasized in PILOT. These activities were designed to improve student
      communication skills, lab skills, and knowledge of molecular biology content.
      Here, we describe the PILOT curriculum and report the results of an anonymous
      assessment survey administered to 75 students who had completed PILOT in the
      previous five semesters. Our data indicate that PILOT provides an effective
      format to expand undergraduate opportunities for research and teaching
      experiences. 

PMID- 23858353
TI  - Assessment of the Impact of the Kansas IDeA Network of Biomedical Research
      Excellence Program on Undergraduate Participation in Research.
AB  - The Kansas IDeA Network of Biomedical Research Excellence (K-INBRE) was
      established in 2001 and is a network of 10 higher-education institutions in
      Kansas and northern Oklahoma. The program is funded by the Institutional
      Development Award (IDeA) program of the National Institutes of Health (NIH). As
      part of the program's goal to enhance the research infrastructure in Kansas, a
      training program was developed to encourage undergraduates to participate in
      biomedical research. From September 2002 to May 2012, the K-INBRE supported 731
      students at 10 institutions. Although 16% of student participants in the program
      are still undergraduates, 323 of our students have gone into biomedical graduate
      school or medical school programs. Thirty-seven percent of all the completed
      students have matriculated into graduate programs and 19% of our completed
      students went to medical school. Moreover, 12% have gone into other health
      related professions. One percent of our students who went into medical school
      programs are in highly prestigious MD/PhD programs. In the fall of 2011, we
      surveyed participants from the last 10 years about career choices and the impact
      of the K-INBRE program on those students. Two hundred twenty-four former and
      current students responded to the survey with a consensus of high impact of the K
      INBRE program on student training, career choices, and perceptions about
      research. 

PMID- 23858354
TI  - Examining an online microbiology game as an effective tool for teaching the
      scientific process.
AB  - This study investigates the effectiveness of the online Flash game Disease
      Defenders in producing knowledge gains for concepts related to the scientific
      process. Disease Defenders was specifically designed to model how the scientific
      process is central to a variety of disciplines and science careers. An additional
      question relates to the game's ability to shift attitudes toward science. Middle
      school classes from grades six to eight were assigned to the experimental group
      (n = 489) or control group (n = 367) and asked to participate in a three-session
      intervention. The sessions involved completing a pretest, a game play session,
      and taking a posttest. Students in the experimental group played Disease
      Defenders while students in the control group played an alternative science game.
      Results showed a significant increase in mean science knowledge scores for all
      grades in the experimental group, with sixth grade and seventh grade students
      gaining more knowledge than eighth grade students. Additionally, results showed a
      significant positive change in science attitudes only among sixth graders, who
      also rated their satisfaction with the game more favorably than students in
      higher grades. No differences in mean test scores were found between genders for
      science knowledge or science attitudes, suggesting that the game is equally
      effective for males and females. 

PMID- 23858355
TI  - Using primary literature to teach science literacy to introductory biology
      students.
AB  - Undergraduate students struggle to read the scientific literature and educators
      have suggested that this may reflect deficiencies in their science literacy
      skills. In this two-year study we develop and test a strategy for using the
      scientific literature to teach science literacy skills to novice life science
      majors. The first year of the project served as a preliminary investigation in
      which we evaluated student science literacy skills, created a set of science
      literacy learning objectives aligned with Bloom's taxonomy, and developed a set
      of homework assignments that used peer-reviewed articles to teach science
      literacy. In the second year of the project the effectiveness of the assignments
      and the learning objectives were evaluated. Summative student learning was
      evaluated in the second year on a final exam. The mean score was 83.5% (+/-20.3%)
      and there were significant learning gains (p < 0.05) in seven of nine of science
      literacy skills. Project data indicated that even though students achieved course
      targeted lower-order science literacy objectives, many were deficient in higher
      order literacy skills. Results of this project suggest that building scientific
      literacy is a continuing process which begins in first-year science courses with
      a set of fundamental skills that can serve the progressive development of
      literacy skills throughout the undergraduate curriculum. 

PMID- 23858356
TI  - Biosafety guidelines for handling microorganisms in the teaching laboratory:
      development and rationale.
AB  - The safe handling of microorganisms in the teaching laboratory is a top priority.
      However, in the absence of a standard set of biosafety guidelines tailored to the
      teaching laboratory, individual educators and institutions have been left to
      develop their own plans. This has resulted in a lack of consistency, and
      differing levels of biosafety practices across institutions. Influenced by the
      lack of clear guidelines and a recent outbreak of Salmonella infections that was
      traced back to teaching laboratory exposures, the Education Board of the American
      Society for Microbiology charged a task force to develop a uniform set of
      biosafety guidelines for working with microorganisms in the teaching laboratory.
      These guidelines represent best practices for safely handling microbes, based on
      the safety requirements found in the Centers for Disease Control and Prevention's
      (CDC's) Biosafety in Microbiological and Biomedical Laboratories (BMBL).
      Guidelines for safely handling microbes at both biosafety level 1 (BSL1) and
      biosafety level 2 (BSL2) were developed. The guidelines are brief by design for
      ease of use and are accompanied by an extensive appendix containing explanatory
      notes, sample documents, and additional resources. These guidelines provide
      educators with a clear and consistent way to safely work with microorganisms in
      the teaching laboratory. 

PMID- 23858357
TI  - An undergraduate laboratory activity demonstrating bacteriophage specificity.
AB  - Bacteriophage are among the most diverse and numerous microbes inhabiting our
      planet. Yet many laboratory activities fail to engage students in meaningful
      exploration of their diversity, unique characteristics, and abundance. In this
      curriculum activity students use a standard plaque assay to enumerate
      bacteriophage particles from a natural sample and use the scientific method to
      address questions about host specificity and diversity. A raw primary sewage
      sample is enriched for bacteriophage using hosts in the family
      Enterobacteriaceae. Students hypothesize about host specificity and use
      quantitative data (serial dilution and plaque assay) to test their hypotheses.
      Combined class data also help them answer questions about phage diversity. The
      exercise was field tested with a class of 47 students using pre- and posttests.
      For all learning outcomes posttest scores were higher than pretest scores at or
      below p = 0.01. Average individualized learning gain (G) was also calculated for
      each learning outcome. Students' use of scientific language in reference to
      bacteriophage and host interaction significantly improved (p = 0.002; G = 0.50).
      Improved means of expression helped students construct better hypotheses on phage
      host specificity (G = 0.31, p = 0.01) and to explain the plaque assay method (G =
      0.33, p = 0.002). At the end of the exercise students also demonstrated improved
      knowledge and understanding of phage specificity as related to phage therapy in
      humans (p < 0.001; G = 51). 

PMID- 23858358
TI  - Using PCR to Target Misconceptions about Gene Expression.
AB  - We present a PCR-based laboratory exercise that can be used with first- or second
      year biology students to help overcome common misconceptions about gene
      expression. Biology students typically do not have a clear understanding of the
      difference between genes (DNA) and gene expression (mRNA/protein) and often
      believe that genes exist in an organism or cell only when they are expressed.
      This laboratory exercise allows students to carry out a PCR-based experiment
      designed to challenge their misunderstanding of the difference between genes and
      gene expression. Students first transform E. coli with an inducible GFP gene
      containing plasmid and observe induced and un-induced colonies. The following
      exercise creates cognitive dissonance when actual PCR results contradict their
      initial (incorrect) predictions of the presence of the GFP gene in transformed
      cells. Field testing of this laboratory exercise resulted in learning gains on
      both knowledge and application questions on concepts related to genes and gene
      expression. 

PMID- 23858359
TI  - Using Student-Produced Time-Lapse Plant Movies to communicate concepts in Plant
      Biology.

PMID- 23858360
TI  - Teaching Microbial Identification with Matrix-Assisted Laser
      Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) and
      Bioinformatics Tools.

PMID- 23858361
TI  - Engaging students in a bioinformatics activity to introduce gene structure and
      function.

PMID- 23858362
TI  - The bad bugs book club: science, literacy, and engagement.

PMID- 23858363
TI  - Using Interactive Animations to Enhance Teaching, Learning, and Retention of
      Respiration Pathway Concepts in Face-to-Face and Online High School,
      Undergraduate, and Continuing Education Learning Environments.

PMID- 23858364
TI  - A poster-session review to reinforce course concepts and improve scientific
      communication skills.

PMID- 23858365
TI  - Using author bylines and concept maps to illustrate the connectedness of
      scientists.

PMID- 23858366
TI  - Observing Fluorescent Probes in Living Cells using a Low-Cost LED Flashlight
      Retrofitted to a Common Vintage Light Microscope.

PMID- 23858367
TI  - Making the basic microbiology laboratory an exciting and engaging experience.

PMID- 23858368
TI  - Looking for the forest and the trees : exercises to provoke abstract thinking.

PMID- 23858369
TI  - Impact of a service-Learning Project on student success in Allied Health
      Microbiology course.

PMID- 23858370
TI  - Bioremediation Approaches in a Laboratory Activity for the Industrial
      Biotechnology and Applied Microbiology (IBAM) Course.

PMID- 23858372
TI  - The newest educational and engaging on-line resources for students and
      instructors from national geographic education.

PMID- 23858373
TI  - Two virtual labs to study genetic inheritance in the fruit fly.

PMID- 23858374
TI  - Endoscopic treatments for chronic radiation proctitis.
AB  - Chronic radiation proctitis is a complication that occurs in patients who receive
      radiation therapy for pelvic malignancies. The common presentation is with rectal
      bleeding, but also rectal pain, diarrhea, tenesmus and even passage of mucus can
      occur. The optimal treatment of bleeding due to radiation proctitis remains
      unclear. Among various therapeutic options, medical management is generally
      ineffective and surgical intervention has a high incidence of morbidity.
      Promising advances have been made in endoscopic therapy, including argon plasma
      coagulation (APC), formalin application as well as new techniques such as
      radiofrequency ablation and cryoablation. APC is a safe, highly effective and
      long-lasting therapy in patients with rectal bleeding associated with radiation
      proctitis. It has been shown that several sessions of APC reduce the rate of
      bleeding and therefore the blood transfusion requirements. Moreover, the effect
      of treatment is long lasting. However, best results are achieved in patients with
      mild to moderate radiation proctitis, leaving space for alternative treatments
      for patients with more severe disease. In patients with severe or refractory
      radiation proctitis intra rectal formalin application is an appropriate treatment
      option. Radiofrequency ablation and cryoablation have shown efficacy as
      alternative methods in a limited number of patients with refractory chronic
      radiation proctitis. 

PMID- 23858375
TI  - Implementation of a polling protocol for predicting celiac disease in
      videocapsule analysis.
AB  - AIM: To investigate the presence of small intestinal villous atrophy in celiac
      disease patients from quantitative analysis of videocapsule image sequences.
      METHODS: Nine celiac patient data with biopsy-proven villous atrophy and seven
      control patient data lacking villous atrophy were used for analysis. Celiacs had
      biopsy-proven disease with scores of Marsh II-IIIC except in the case of one
      hemophiliac patient. At four small intestinal levels (duodenal bulb, distal
      duodenum, jejunum, and ileum), video clips of length 200 frames (100 s) were
      analyzed. Twenty-four measurements were used for image characterization. These
      measurements were determined by quantitatively processing the videocapsule images
      via techniques for texture analysis, motility estimation, volumetric
      reconstruction using shape-from-shading principles, and image transformation.
      Each automated measurement method, or automaton, was polled as to whether or not
      villous atrophy was present in the small intestine, indicating celiac disease.
      Each automaton's vote was determined based upon an optimized parameter threshold
      level, with the threshold levels being determined from prior data. A prediction
      of villous atrophy was made if it received the majority of votes (>= 13), while
      no prediction was made for tie votes (12-12). Thus each set of images was
      classified as being from either a celiac disease patient or from a control
      patient. RESULTS: Separated by intestinal level, the overall sensitivity of
      automata polling for predicting villous atrophy and hence celiac disease was
      83.9%, while the specificity was 92.9%, and the overall accuracy of automata
      based polling was 88.1%. The method of image transformation yielded the highest
      sensitivity at 93.8%, while the method of texture analysis using subbands had the
      highest specificity at 76.0%. Similar results of prediction were observed at all
      four small intestinal locations, but there were more tie votes at location 4
      (ileum). Incorrect prediction which reduced sensitivity occurred for two celiac
      patients with Marsh type II pattern, which is characterized by crypt hyperplasia,
      but normal villous architecture. Pooled from all levels, there was a mean of
      14.31 +/- 3.28 automaton votes for celiac vs 9.67 +/- 3.31 automaton votes for
      control when celiac patient data was analyzed (P < 0.001). Pooled from all
      levels, there was a mean of 9.71 +/- 2.8128 automaton votes for celiac vs 14.32
      +/- 2.7931 automaton votes for control when control patient data was analyzed (P
      < 0.001). CONCLUSION: Automata-based polling may be useful to indicate presence
      of mucosal atrophy, indicative of celiac disease, across the entire small bowel,
      though this must be confirmed in a larger patient set. Since the method is
      quantitative and automated, it can potentially eliminate observer bias and enable
      the detection of subtle abnormality in patients lacking a clear diagnosis. Our
      paradigm was found to be more efficacious at proximal small intestinal locations,
      which may suggest a greater presence and severity of villous atrophy at proximal
      as compared with distal locations.

PMID- 23858376
TI  - Reliability in endoscopic diagnosis of portal hypertensive gastropathy.
AB  - AIM: To analyze reliability among endoscopists in diagnosing portal hypertensive
      gastropathy (PHG) and to determine which criteria from the most utilized
      classifications are the most suitable. METHODS: From January to July 2009, in an
      academic quaternary referral center at Santa Casa of Sao Paulo Endoscopy Service,
      Brazil, we performed this single-center prospective study. In this period, we
      included 100 patients, including 50 sequential patients who had portal
      hypertension of various etiologies; who were previously diagnosed based on
      clinical, laboratory and imaging exams; and who presented with esophageal
      varices. In addition, our study included 50 sequential patients who had dyspeptic
      symptoms and were referred for upper digestive endoscopy without portal
      hypertension. All subjects underwent upper digestive endoscopy, and the images of
      the exam were digitally recorded. Five endoscopists with more than 15 years of
      experience answered an electronic questionnaire, which included endoscopic
      criteria from the 3 most commonly used Portal Hypertensive Gastropathy
      classifications (McCormack, NIEC and Baveno) and the presence of elevated or flat
      antral erosive gastritis. All five endoscopists were blinded to the patients'
      clinical information, and all images of varices were deliberately excluded for
      the analysis. RESULTS: The three most common etiologies of portal hypertension
      were schistosomiasis (36%), alcoholic cirrhosis (20%) and viral cirrhosis (14%).
      Of the 50 patients with portal hypertension, 84% were Child A, 12% were Child B,
      4% were Child C, 64% exhibited previous variceal bleeding and 66% were previously
      endoscopic treated. The endoscopic parameters, presence or absence of mosaic-like
      pattern, red point lesions and cherry-red spots were associated with high inter
      observer reliability and high specificity for diagnosing Portal Hypertensive
      Gastropathy. Sensitivity, specificity and reliability for the diagnosis of PHG
      (%) were as follows: mosaic-like pattern (100; 92.21; High); fine pink speckling
      (56; 76.62; Unsatisfactory); superficial reddening (69.57; 66.23;
      Unsatisfactory); red-point lesions (47.83; 90.91; High); cherry-red spots (39.13;
      96.10; High); isolated red marks (43.48; 88.31; High); and confluent red marks
      (21.74; 100; Unsatisfactory). Antral elevated erosive gastritis exhibited high
      reliability and high specificity with respect to the presence of portal
      hypertension (92%) and the diagnosis of portal hypertensive gastropathy (88.31%).
      CONCLUSION: The most suitable endoscopic criteria for the diagnosis of PHG were
      mosaic-like pattern, red-point lesions and cherry-red spots with no subdivisions,
      which were associated with a high rate of inter-observer reliability.

PMID- 23858377
TI  - Evaluation of fully covered self-expanding metal stents in benign biliary
      strictures and bile leaks.
AB  - AIM: To investigate the use of fully covered metal stents in benign biliary
      strictures (BBS) and bile leaks. METHODS: We studied 17 patients, at Harbor-UCLA
      Medical center (Los Angeles), with BBS (n = 12) and bile leaks (n = 5) from July
      2007 to February 2012 that had received placement of fully covered self-expanding
      metal stents (FCSEMs). Fourteen patients had endoscopic placement of VIABIL((r))
      (Conmed, Utica, New York, United States) stents and three had Wallflex((r))
      (Boston Scientific, Mass) stents. FCSEMS were 8 mm or 10 mm in diameter and 4 cm
      to 10 cm in length. Patients were followed at regular intervals to evaluate for
      symptoms and liver function tests. FCSEMS were removed after 4 or more weeks.
      Resolution of BBS and leak was documented cholangiographically following stent
      removal. Stent patency can be defined as adequate bile and contrast flow from the
      stent and into the ampulla during endoscopic retrograde cholangiopancreatography
      (ERCP) without clinical signs and/or symptoms of biliary obstruction. Criterion
      for bile leak resolution at ERCP is defined as absence of contrast extravasation
      from the common bile duct, cystic duct remanent, or gall bladder fossa. Rate of
      complications such as migration, and in-stent occlusion were recorded. Failure of
      endoscopic therapy was defined as persistent biliary stenosis or continuous
      biliary leakage after 12 mo of stent placement. RESULTS: All 17 patients
      underwent successful FCSEMS placement and removal. Etiologies of BBS included:
      cholecystectomies (n = 8), cholelithiasis (n = 2), hepatic artery compression (n
      = 1), pancreatitis (n = 2), and Whipple procedure (n = 1). All bile leaks
      occurred following cholecystectomy. The anatomic location of BBS varied: distal
      common bile duct (n = 7), common hepatic duct (n = 1), hepaticojejunal
      anastomosis (n = 2), right intrahepatic duct (n = 1), and choledochoduodenal
      anastomatic junction (n = 1). All bile leaks were found to be at the cystic duct.
      Twelve of 17 patients had failed prior stent placement or exchange. Resolution of
      the biliary strictures and bile leaks was achieved in 16 of 17 patients (94%).
      The overall median stent time was 63 d (range 27-251 d). The median stent time
      for the BBS group and bile leak group was 62 +/- 58 d (range 27-199 d) and 92 +/-
      81 d (range 48-251 d), respectively. All 17 patients underwent successful FCSEMS
      removal. Long term follow-up was obtained for a median of 575 d (range 28-1435
      d). Complications occurred in 5 of 17 patients (29%) and included: migration (n =
      2), stent clogging (n = 1), cholangitis (n = 1), and sepsis with hepatic abscess
      (n = 1). CONCLUSION: Placement of fully covered self-expanding metal stents may
      be used in the management of benign biliary strictures and bile leaks with a low
      rate of complications.

PMID- 23858378
TI  - Successful treatment of cervical esophageal leakage by endoscopic-vacuum assisted
      closure therapy.
AB  - AIM: To evaluate the efficacy and safety of endoscopic-vacuum assisted closure (E
      VAC) therapy in the treatment of cervical esophageal leakage. METHODS: Between
      May and November 2012, three male patients who developed post-operative cervical
      esophageal leakage were treated with E-VAC therapy. One patient had undergone
      surgical excision of a pharyngo-cervical liposarcoma with partial esophageal
      resection, and the other two patients had received surgical treatment for
      symptomatic Zenker's diverticulum. Following endoscopic verification of the
      leakage, a trimmed polyurethane sponge was fixed to the distal end of a
      nasogastric silicone tube and endoscopically positioned into the wound cavity,
      and with decreasing cavity size the sponge was positioned intraluminally to cover
      the leak. Continuous suction was applied, and the vacuum drainage system was
      changed twice a week. RESULTS: The initial E-VAC placement was technically
      successful for all three patients, and complete closure of the esophageal leak
      was achieved without any procedure-related complications. In all three patients,
      the insufficiencies were located either above or slightly below the upper
      esophageal sphincter. The median duration of the E-VAC drainage was 29 d (range:
      19-49 d), with a median of seven sponge exchanges (range: 5-12 sponge exchanges).
      In addition, the E-VAC therapy reduced inflammatory markers to within normal
      range for all three patients. Two of the patients were immediately fitted with a
      percutaneous enteral gastric feeding tube with jejunal extension, and the third
      patient received parenteral feeding. All three patients showed normal swallow
      function and no evidence of stricture after completion of the E-VAC therapy.
      CONCLUSION: E-VAC therapy for cervical esophageal leakage was well tolerated by
      patients. This safe and effective procedure may significantly reduce morbidity
      and mortality following cervical esophageal leakage.

PMID- 23858379
TI  - Ultrathin endoscope flexibility can predict discomfort associated with unsedated
      transnasal esophagogastroduodenoscopy.
AB  - AIM: To evaluate the effects of choice of insertion route and ultrathin endoscope
      types. METHODS: This prospective study (January-June 2012) included 882
      consecutive patients who underwent annual health checkups. Transnasal
      esophagogastroduodenoscopy (EGD) was performed in 503 patients and transoral EGD
      in 235 patients using six types of ultrathin endoscopes. Patients were given a
      choice of insertion route, either transoral or transnasal, prior to EGD
      examination. For transoral insertion, the endoscope was equipped with a thin-type
      mouthpiece and tongue depressor. Conscious sedation was not used for any patient.
      EGD-associated discomfort was assessed using a visual analog scale (VAS; no
      discomfort 0- maximum discomfort 10). RESULTS: Rates of preference for transnasal
      insertion were significantly higher in male (male/female 299/204 vs 118/117) and
      younger patients (56.8 +/- 11.2 years vs 61.3 +/- 13.0 years), although no
      significant difference was found in VAS scores between transoral and transnasal
      insertion (3.9 +/- 2.3 vs 4.1 +/- 2.5). Multivariate analysis revealed that
      gender, age, operator, and endoscope were independent significant predictors of
      VAS for transnasal insertion, although gender, age, and endoscope were those for
      transoral insertion. Further analysis revealed only the endoscopic flexibility
      index (EFI) as an independent significant predictor of VAS for transnasal
      insertion. Both EFI and tip diameter were independent significant predictors of
      VAS for transoral insertion. CONCLUSION: Flexibility of ultrathin endoscopes can
      be a predictor of EGD-associated discomfort, especially in transnasal insertion.

PMID- 23858380
TI  - Longest duration of retention of video capsule: A case report and literature
      review.
AB  - Video capsule endoscopy (VCE) is a safe innovative tool for investigating obscure
      gastrointestinal bleeding, Crohn's disease and other small bowel pathologies. The
      capsule is usually excreted with faeces within 24-48 h. Retention of capsule
      rarely occurs, and it usually depends on the indication of VCE. The longest
      reported case of capsule retention in the literature is 2.5 years. Surgical
      approach is considered effective to retrieve the retained capsule. We present a
      case of asymptomatic retention of capsule for four and half years in a 49-year
      old man who underwent VCE to explore the cause of obscure gastrointestinal
      bleeding. It was successfully retrieved endoscopically. We will also briefly
      review the literature regarding the causes, different presentations and
      management of capsule retention. 

PMID- 23858381
TI  - Oldest biliary endoprosthesis in situ.
AB  - The advantages of endoscopic retrograde cholangiopancreatography over open
      surgery have made it the predominant method of treating patients with
      choledocholithiasis. After sphincterotomy, however, 10%-15% of common bile duct
      stones cannot be removed with a basket or balloon. The methods for managing
      "irretrievable stones" include surgery, mechanical lithotripsy, intraductal or
      extracorporeal shock wave lithotripsy and biliary stenting. The case presented
      was a referred 82-year-old Caucasian woman with a 7-year-old plastic biliary
      endoprosthesis in situ. To the best of our knowledge the examined endoprosthesis
      is the oldest endoprosthesis in situ reported in the literature. Endoscopic
      biliary endoprosthesis placement remains a simple and safe procedure for patients
      with stones that are difficult to manage by conventional endoscopic methods and
      for patients who are unfit for surgery or who are high surgical risks. To date no
      consensus has been reached regarding how long a biliary prosthesis should remain
      in situ. Long-term biliary stenting may have a role in selected elderly patients
      if stones extraction has failed because the procedure may prevent stones
      impaction and cholangitis. 

PMID- 23858382
TI  - A meta-analysis of telemedicine success in Africa.
AB  - The use of information and communication technologies (ICT) tools to improve the
      efficiency of professionalism at work is increasing every time under the dynamic
      digital environment. Tools such as telemedicine, tele-education, and health
      informatics have of late been incorporated in the health sector to enable easy
      access to essential services, for example, in medical areas from referral centers
      by the patients on one hand and enabling the doctor to doctor consultations for
      the benefit of patients. Unfortunately, observations indicate dearth efforts and
      commitment to optimize use of the tools in the majority of the countries south of
      the Sahara. Sub-Saharan Africa has been left almost behind the rest of the world
      in terms of development going through decades of economic exploitation by
      especially the west through its natural and human resources. These factors,
      ethnic conflicts and endless wars have continued to ruin sub-Saharan Africa's
      socio-economic development. Information was obtained through a network of
      telemedicine practitioners in different African countries using internet
      communication, through E-mail and reviewing existing literature of their
      activities. This information was compiled from representative countries in each
      African region and the previous authors'experiences as telemedicine practioners.
      Most of these countries have inadequate ICT infrastructure, which yet creates sub
      optimal application. Sub-Saharan Africa, made up of 33 of the 48 global poorest
      countries has to extend its ICT diffusion and policy to match the ever developing
      global economy. In some countries such as Ethiopia and South Africa there is
      significant progress in Telemedicine while in countries such as Burkina Faso and
      Nigeria the progress is slow because of lack of political support. Almost all
      reference to Africa is made in due respect to sub-Saharan Africa, one with big
      social, economic, and political problems with resultant high morbidity and
      mortality rates. This also highlights the under-representation of African
      researchers in the global whelm of information system research. Telemedicine in
      Africa though has not attracted enough political support is potentially a very
      useful conduit of health-care given the fact that the continent is resource
      limited and still enduring the effects of scarce human resource especially in
      health. 

PMID- 23858383
TI  - Mitosis detection in breast cancer histological images An ICPR 2012 contest.
AB  - INTRODUCTION: In the framework of the Cognitive Microscope (MICO) project, we
      have set up a contest about mitosis detection in images of H and E stained slides
      of breast cancer for the conference ICPR 2012. Mitotic count is an important
      parameter for the prognosis of breast cancer. However, mitosis detection in
      digital histopathology is a challenging problem that needs a deeper study.
      Indeed, mitosis detection is difficult because mitosis are small objects with a
      large variety of shapes, and they can thus be easily confused with some other
      objects or artefacts present in the image. We added a further dimension to the
      contest by using two different slide scanners having different resolutions and
      producing red-green-blue (RGB) images, and a multi-spectral microscope producing
      images in 10 different spectral bands and 17 layers Z-stack. 17 teams
      participated in the study and the best team achieved a recall rate of 0.7 and
      precision of 0.89. CONTEXT: Several studies on automatic tools to process
      digitized slides have been reported focusing mainly on nuclei or tubule
      detection. Mitosis detection is a challenging problem that has not yet been
      addressed well in the literature. AIMS: Mitotic count is an important parameter
      in breast cancer grading as it gives an evaluation of the aggressiveness of the
      tumor. However, consistency, reproducibility and agreement on mitotic count for
      the same slide can vary largely among pathologists. An automatic tool for this
      task may help for reaching a better consistency, and at the same time reducing
      the burden of this demanding task for the pathologists. SUBJECTS AND METHODS:
      Professor Friotadiotarique Capron team of the pathology department at Pitiiota
      Salpkappatrithetare Hospital in Paris, France, has selected a set of five slides
      of breast cancer. The slides are stained with H and E. They have been scanned by
      three different equipments: Aperio ScanScope XT slide scanner, Hamamatsu
      NanoZoomer 2.0-HT slide scanner and 10 bands multispectral microscope. The data
      set is made up of 50 high power fields (HPF) coming from 5 different slides
      scanned at *40 magnification. There are 10 HPFs/slide. The pathologist has
      annotated all the mitotic cells manually. A HPF has a size of 512 MUm * 512 MUm
      (that is an area of 0.262 mm (2) , which is a surface equivalent to that of a
      microscope field diameter of 0.58 mm. These 50 HPFs contain a total of 326
      mitotic cells on images of both scanners, and 322 mitotic cells on the
      multispectral microscope. RESULTS: Up to 129 teams have registered to the
      contest. However, only 17 teams submitted their detection of mitotic cells. The
      performance of the best team is very promising, with F-measure as high as 0.78.
      However, the database we provided is by far too small for a good assessment of
      reliability and robustness of the proposed algorithms. CONCLUSIONS: Mitotic count
      is an important criterion in the grading of many types of cancers, however, very
      little research has been made on automatic mitotic cell detection, mainly because
      of a lack of available data. A main objective of this contest was to propose a
      database of mitotic cells on digitized breast cancer histopathology slides to
      initiate works on automated mitotic cell detection. In the future, we would like
      to extend this database to have much more images from different patients and also
      for different types of cancers. In addition, mitotic cells should be annotated by
      several pathologists to reflect the partial agreement among them.

PMID- 23858384
TI  - Classification of mitotic figures with convolutional neural networks and seeded
      blob features.
AB  - BACKGROUND: The mitotic figure recognition contest at the 2012 International
      Conference on Pattern Recognition (ICPR) challenges a system to identify all
      mitotic figures in a region of interest of hematoxylin and eosin stained tissue,
      using each of three scanners (Aperio, Hamamatsu, and multispectral). METHODS: Our
      approach combines manually designed nuclear features with the learned features
      extracted by convolutional neural networks (CNN). The nuclear features capture
      color, texture, and shape information of segmented regions around a nucleus. The
      use of a CNN handles the variety of appearances of mitotic figures and decreases
      sensitivity to the manually crafted features and thresholds. RESULTS: On the test
      set provided by the contest, the trained system achieves F1 scores up to 0.659 on
      color scanners and 0.589 on multispectral scanner. CONCLUSIONS: We demonstrate a
      powerful technique combining segmentation-based features with CNN, identifying
      the majority of mitotic figures with a fair precision. Further, we show that the
      approach accommodates information from the additional focal planes and spectral
      bands from a multi-spectral scanner without major redesign.

PMID- 23858385
TI  - Automated mitosis detection in histopathology using morphological and multi
      channel statistics features.
AB  - CONTEXT: According to Nottingham grading system, mitosis count plays a critical
      role in cancer diagnosis and grading. Manual counting of mitosis is tedious and
      subject to considerable inter- and intra-reader variations. AIMS: The aim is to
      improve the accuracy of mitosis detection by selecting the color channels that
      better capture the statistical and morphological features, which classify mitosis
      from other objects. MATERIALS AND METHODS: We propose a framework that includes
      comprehensive analysis of statistics and morphological features in selected
      channels of various color spaces that assist pathologists in mitosis detection.
      In candidate detection phase, we perform Laplacian of Gaussian, thresholding,
      morphology and active contour model on blue-ratio image to detect and segment
      candidates. In candidate classification phase, we extract a total of 143 features
      including morphological, first order and second order (texture) statistics
      features for each candidate in selected channels and finally classify using
      decision tree classifier. RESULTS AND DISCUSSION: The proposed method has been
      evaluated on Mitosis Detection in Breast Cancer Histological Images (MITOS)
      dataset provided for an International Conference on Pattern Recognition 2012
      contest and achieved 74% and 71% detection rate, 70% and 56% precision and 72%
      and 63% F-Measure on Aperio and Hamamatsu images, respectively. CONCLUSIONS AND
      FUTURE WORK: The proposed multi-channel features computation scheme uses fixed
      image scale and extracts nuclei features in selected channels of various color
      spaces. This simple but robust model has proven to be highly efficient in
      capturing multi-channels statistical features for mitosis detection, during the
      MITOS international benchmark. Indeed, the mitosis detection of critical
      importance in cancer diagnosis is a very challenging visual task. In future work,
      we plan to use color deconvolution as preprocessing and Hough transform or local
      extrema based candidate detection in order to reduce the number of candidates in
      mitosis and non-mitosis classes.

PMID- 23858386
TI  - A gamma-gaussian mixture model for detection of mitotic cells in breast cancer
      histopathology images.
AB  - In this paper, we propose a statistical approach for mitosis detection in breast
      cancer histological images. The proposed algorithm models the pixel intensities
      in mitotic and non-mitotic regions by a Gamma-Gaussian mixture model (GGMM) and
      employs a context aware post-processing (CAPP) in order to reduce false
      positives. Experimental results demonstrate the ability of this simple, yet
      effective method to detect mitotic cells (MCs) in standard H & E breast cancer
      histology images. CONTEXT: Counting of MCs in breast cancer histopathology images
      is one of three components (the other two being tubule formation, nuclear
      pleomorphism) required for developing computer assisted grading of breast cancer
      tissue slides. This is very challenging since the biological variability of the
      MCs makes their detection extremely difficult. In addition, if standard H & E is
      used (which stains chromatin rich structures, such as nucleus, apoptotic, and MCs
      dark blue) and it becomes extremely difficult to detect the latter given the fact
      that former two are densely localized in the tissue sections. AIMS: In this
      paper, a robust MCs detection technique is developed and tested on 35 breast
      histopathology images, belonging to five different tissue slides. SETTINGS AND
      DESIGN: Our approach mimics a pathologists' approach to MCs detections. The idea
      is (1) to isolate tumor areas from non-tumor areas
      (lymphoid/inflammatory/apoptotic cells), (2) search for MCs in the reduced space
      by statistically modeling the pixel intensities from mitotic and non-mitotic
      regions, and finally (3) evaluate the context of each potential MC in terms of
      its texture. MATERIALS AND METHODS: Our experimental dataset consisted of 35
      digitized images of breast cancer biopsy slides with paraffin embedded sections
      stained with H and E and scanned at * 40 using an Aperio scanscope slide scanner.
      STATISTICAL ANALYSIS USED: We propose GGMM for detecting MCs in breast histology
      images. Image intensities are modeled as random variables sampled from one of the
      two distributions; Gamma and Gaussian. Intensities from MCs are modeled by a
      gamma distribution and those from non-mitotic regions are modeled by a gaussian
      distribution. The choice of Gamma-Gaussian distribution is mainly due to the
      observation that the characteristics of the distribution match well with the data
      it models. The experimental results show that the proposed system achieves a high
      sensitivity of 0.82 with positive predictive value (PPV) of 0.29. Employing CAPP
      on these results produce 241% increase in PPV at the cost of less than 15%
      decrease in sensitivity. CONCLUSIONS: In this paper, we presented a GGMM for
      detection of MCs in breast cancer histopathological images. In addition, we
      introduced CAPP as a tool to increase the PPV with a minimal loss in sensitivity.
      We evaluated the performance of the proposed detection algorithm in terms of
      sensitivity and PPV over a set of 35 breast histology images selected from five
      different tissue slides and showed that a reasonably high value of sensitivity
      can be retained while increasing the PPV. Our future work will aim at increasing
      the PPV further by modeling the spatial appearance of regions surrounding mitotic
      events.

PMID- 23858387
TI  - Mitosis detection using generic features and an ensemble of cascade adaboosts.
AB  - CONTEXT: Mitosis count is one of the factors that pathologists use to assess the
      risk of metastasis and survival of the patients, which are affected by the breast
      cancer. AIMS: We investigate an application of a set of generic features and an
      ensemble of cascade adaboosts to the automated mitosis detection. Calculation of
      the features rely minimally on object-level descriptions and thus require minimal
      segmentation. MATERIALS AND METHODS: The proposed work was developed and tested
      on International Conference on Pattern Recognition (ICPR) 2012 mitosis detection
      contest data. STATISTICAL ANALYSIS USED: We plotted receiver operating
      characteristics curves of true positive versus false positive rates; calculated
      recall, precision, F-measure, and region overlap ratio measures. RESULTS: WE
      TESTED OUR FEATURES WITH TWO DIFFERENT CLASSIFIER CONFIGURATIONS: 1) An ensemble
      of single adaboosts, 2) an ensemble of cascade adaboosts. On the ICPR 2012
      mitosis detection contest evaluation, the cascade ensemble scored 54, 62.7, and
      58, whereas the non-cascade version scored 68, 28.1, and 39.7 for the recall,
      precision, and F-measure measures, respectively. Mostly used features in the
      adaboost classifier rules were a shape-based feature, which counted granularity
      and a color-based feature, which relied on Red, Green, and Blue channel
      statistics. CONCLUSIONS: The features, which express the granular structure and
      color variations, are found useful for mitosis detection. The ensemble of
      adaboosts performs better than the individual adaboost classifiers. Moreover, the
      ensemble of cascaded adaboosts was better than the ensemble of single adaboosts
      for mitosis detection.

PMID- 23858388
TI  - The (not yet) willingly adopted tool.

PMID- 23858389
TI  - Performance of CellaVision DM96 in leukocyte classification.
AB  - BACKGROUND: Leukocyte differentials are an important component of clinical care.
      Morphologic assessment of peripheral blood smears (PBS) may be required to
      accurately classify leukocytes. However, manual microscopy is labor intensive.
      The CellaVision DM96 is an automated system that acquires digital images of
      leukocytes on PBS, pre-classifies the cell type, and displays them on screen for
      a Technologist or Pathologist to approve or reclassify. Our study compares the
      results of the DM96 with manual microscopy. METHODS: Three hundred and fifty-nine
      PBS were selected and assessed by manual microscopy with a 200 leukocyte cell
      count. They were then reassessed using the CellaVision DM96 with a 115 leukocyte
      cell count including reclassification when necessary. Correlation between the
      manual microscopy results and the CellaVision DM96 results was calculated for
      each cell type. RESULTS: The correlation coefficients (r (2)) range from a high
      of 0.99 for blasts to a low of 0.72 for metamyelocytes. CONCLUSIONS: The
      correlation between the CellaVision DM96 and manual microscopy was as good or
      better than the previously published data. The accuracy of leukocyte
      classification depended on the cell type, and in general, there was lower
      correlation for rare cell types. However, the correlation is similar to previous
      studies on the correlation of manual microscopy with an established reference
      result. Therefore, the CellaVision DM96 is appropriate for clinical
      implementation.

PMID- 23858390
TI  - Going fully digital: Perspective of a Dutch academic pathology lab.
AB  - During the last years, whole slide imaging has become more affordable and widely
      accepted in pathology labs. Digital slides are increasingly being used for
      digital archiving of routinely produced clinical slides, remote consultation and
      tumor boards, and quantitative image analysis for research purposes and in
      education. However, the implementation of a fully digital Pathology Department
      requires an in depth look into the suitability of digital slides for routine
      clinical use (the image quality of the produced digital slides and the factors
      that affect it) and the required infrastructure to support such use (the storage
      requirements and integration with lab management and hospital information
      systems). Optimization of digital pathology workflow requires communication
      between several systems, which can be facilitated by the use of open standards
      for digital slide storage and scanner management. Consideration of these aspects
      along with appropriate validation of the use of digital slides for routine
      pathology can pave the way for pathology departments to go "fully digital." In
      this paper, we summarize our experiences so far in the process of implementing a
      fully digital workflow at our Pathology Department and the steps that are needed
      to complete this process. 

PMID- 23858391
TI  - Platelet count estimation using the CellaVision DM96 system.
AB  - INTRODUCTION: Rapid and accurate determination of platelet count is an important
      factor in diagnostic medicine. Traditional microscopic methods are labor
      intensive with variable results and are highly dependent on the individual
      training. Recent developments in automated peripheral blood differentials using a
      computerized system have shown many advantages as a viable alternative. The
      purpose of this paper was to determine the reliability and accuracy of the
      CellaVision DM 96 system with regards to platelet counts. MATERIALS AND METHODS:
      One hundred twenty seven peripheral blood smears were analyzed for platelet count
      by manual microscopy, an automated hematology analyzer (Beckman Counter LH 780 or
      Unicel DXH 800 analyzers) and with the CellaVision DM96 system. Results were
      compared using the correlations and Bland-Altman plots. RESULTS: Platelet counts
      from the DM96 system showed an R(2) of 0.94 when compared to manual platelet
      estimates and an R(2) of 0.92 when compared to the automated hematology analyzer
      results. Bland-Altman plots did not show any systematic bias.

PMID- 23858392
TI  - Prevalence and Perceived Financial Costs of Marijuana versus Tobacco use among
      Urban Low-Income Pregnant Women.
AB  - OBJECTIVE: To examine the relative prevalence of marijuana and tobacco use among
      low-income post-partum women, using self-report, urine, and hair testing data;
      and to further explore perceptions of the substances among postpartum women by
      evaluating perceived risk and monetary cost of prenatal marijuana versus tobacco
      use. METHODS: Data from two studies were available for a total of 100 (Study 1)
      and 50 (Study 2) low-income, primarily African-American post-partum women. Study
      1 participants completed brief self-report measures of substance use as well as
      urine and hair samples; study 2 participants completed a brief opinion survey
      regarding the risks and monetary costs of prenatal marijuana use. RESULTS: In
      Study 1, the self-reported prevalence of any tobacco or marijuana use in the past
      three months was 17% and 11%, respectively. However, objectively-defined
      marijuana use was more prevalent than self-reported tobacco use: 14% tested
      positive for marijuana by urinalysis, and 28% by hair analysis. Study 2
      participants were more likely to believe that there is a safe level of marijuana
      use during pregnancy, and nearly half believed that using marijuana during
      pregnancy was less expensive than smoking cigarettes. CONCLUSION: Marijuana use
      may be as or more prevalent than tobacco use among low-income, African-American
      pregnant women. These findings may in part be attributable to perceptions of
      roughly equivalent cost and the lack of a clear public health message regarding
      prenatal marijuana use, combined with growing pro-marijuana advocacy. A broader
      public health response to address prenatal marijuana use, along with other
      substances of abuse, is needed.

PMID- 23858393
TI  - The management of osteoarthritis in movement disorders: a case discussion.
AB  - BACKGROUND: A 37-year-old female with a hyperkinetic movement disorder due to
      chorea-acanthocytosis developed severe painful degenerative arthritis of her left
      knee as a consequence of repetitive involuntary flexion and extension dystonic
      and ballistic movements. CASE REPORT: Despite profound limitation in her mobility
      a total knee replacement was successfully undertaken. DISCUSSION: The case
      emphasizes that patients with progressive neurodegenerative disorders may derive
      relief or resolution of pain by joint replacement even if mobility does not
      improve following surgery. A multidisciplinary approach to care is essential.

PMID- 23858395
TI  - Toward a universal influenza vaccine: from the perspective of protective
      efficacy.

PMID- 23858396
TI  - Clinical and Experimental Vaccine Research is now registered in PubMed Central,
      PubMed, KoreaMed, and KoreaMed Synapse.

PMID- 23858394
TI  - An update on tardive dyskinesia: from phenomenology to treatment.
AB  - Tardive dyskinesia (TD), characterized by oro-buccal-lingual stereotypy, can
      manifest in the form of akathisia, dystonia, tics, tremor, chorea, or as a
      combination of different types of abnormal movements. In addition to movement
      disorders (including involuntary vocalizations), patients with TD may have a
      variety of sensory symptoms, such as urge to move (as in akathisia),
      paresthesias, and pain. TD is a form of tardive syndrome-a group of iatrogenic
      hyperkinetic and hypokinetic movement disorders caused by dopamine receptor
      blocking agents. The pathophysiology of TD remains poorly understood, and
      treatment of this condition is often challenging. In this update, we provide the
      most current information on the history, nomenclature, etiology, pathophysiology,
      epidemiology, phenomenology, differential diagnosis, and treatment of TD. 

PMID- 23858397
TI  - Paths toward hepatitis B immunization in South Korea and Taiwan.
AB  - South Korea and Taiwan have had similar experiences of economic development in
      the post-war era. The two societies have also successfully overcome the threat of
      liver cancer by using mass hepatitis B vaccinations. However, to reach their
      current states, they followed different directions, and experienced differing
      effects on their national health governance systems. In South Korea, vaccine
      production occurred prior to effectively introducing immunization programs. In
      contrast, Taiwan established an effective immunization program first. However,
      industrialization of vaccines against hepatitis B has failed. Taiwan has to
      import vaccines for domestic use. This article provides a contextual overview on
      the different methods South Korea and Taiwan have used to arrive at their modern
      status of hepatitis B immunization. 

PMID- 23858398
TI  - BCG vaccine in Korea.
AB  - The anti-tuberculosis Bacille de Calmette et Guerin (BCG) vaccine was developed
      between 1905 and 1921 at Pasteur Institutes of Lille in France, and was adopted
      by many countries. BCG strains comprise natural mutants of major virulence
      factors of Mycobacterium tuberculosis and that BCG sub-strains differ markedly in
      virulence levels. The tuberculosis became endemic in Korea after the Korean War
      (1950s). The BCG strain, which was donated by Pasteur Institutes, was brought to
      Korea in 1955, and the first domestic BCG vaccine was produced by the National
      Defense Research Institute (NDRI), current Korea Centers for Disease Control and
      Prevention (KCDC), in 1960. Since 1987, BCG manufacture work was handed over to
      the Korean Institute of Tuberculosis (KIT), the freeze-dried BCG vaccine was
      manufactured at a scale required to meet the whole amount of domestic
      consumption. However, since 2006, the manufacture of BCG vaccine suspended and
      the whole amount of BCG was imported at this point of time. Now KIT is planning
      to re-produce the BCG vaccine in Korea under the supervision of KCDC, this will
      be render great role to National Tuberculosis Control Program (NTP) and provide
      initiating step for developing new tuberculosis vaccines in Korea. 

PMID- 23858399
TI  - Herpes zoster vaccine in Korea.
AB  - Herpes zoster and post-herpetic neuralgia deteriorate the quality of life because
      of severe pain and complications, and cause considerable social and economic
      burden of disease. In 2012, herpes zoster vaccine was released in Korea. The
      efficacy of herpes zoster vaccine is known to be 51.3-66.5% among the aged over
      60 and 69.8-72.4% among adults between 50 and 59. It is also known that
      preventive efficacy is maintained for at least 5 years. Although there can be
      local reactions such as redness, pain and swelling at the site of injection and
      systemic reaction such as headache and eruption after herpes zoster vaccination,
      most of the adverse reactions are minor and disappear within days by themselves.
      As it is a live vaccine, persons with severe immune-suppression and pregnant
      women should not be vaccinated with the vaccine. Currently, Korean Society of
      Infectious Diseases recommended for the aged over 60 to be vaccinated with herpes
      zoster vaccine by subcutaneous route. In this article, clinical aspects and
      burden of disease of herpes zoster, efficacy and effects of herpes zoster
      vaccine, and herpes zoster vaccine recommendation by Korean Society of Infectious
      Diseases are discussed. 

PMID- 23858400
TI  - Viral vectors for vaccine applications.
AB  - Traditional approach of inactivated or live-attenuated vaccine immunization has
      resulted in impressive success in the reduction and control of infectious disease
      outbreaks. However, many pathogens remain less amenable to deal with the
      traditional vaccine strategies, and more appropriate vaccine strategy is in need.
      Recent discoveries that led to increased understanding of viral molecular biology
      and genetics has rendered the used of viruses as vaccine platforms and as
      potential anti-cancer agents. Due to their ability to effectively induce both
      humoral and cell-mediated immune responses, viral vectors are deemed as an
      attractive alternative to the traditional platforms to deliver vaccine antigens
      as well as to specifically target and kill tumor cells. With potential targets
      ranging from cancers to a vast number of infectious diseases, the benefits
      resulting from successful application of viral vectors to prevent and treat human
      diseases can be immense. 

PMID- 23858401
TI  - DNA vaccines targeting human papillomavirus-associated diseases: progresses in
      animal and clinical studies.
AB  - Human papillomavirus (HPV) infection is a major cause of cervical cancer and its
      precancerous diseases. Cervical cancer is the second deadliest cancer killer
      among women worldwide. Moreover, HPV is also known to be a causative agent of
      oral, pharyngeal, anal and genital cancer. Recent application of HPV structural
      protein (L1)-targeted prophylactic vaccines (Gardasil(r) and Cervarix(r)) is
      expected to reduce the incidence of HPV infection and cervical cancer, and
      possibly other HPV-associated cancers. However, the benefit of the prophylactic
      vaccines for treating HPV-infected patients is unlikely, underscoring the
      importance of developing therapeutic vaccines against HPV infection. In this
      regard, numerous types of therapeutic vaccine approaches targeting the HPV
      regulatory proteins, E6 and E7, have been tested for their efficacy in animals
      and clinically. In this communication, we review HPV vaccine types, in particular
      DNA vaccines, their designs and delivery by electroporation and their immunologic
      and antitumor efficacy in animals and humans, along with the basics of HPV and
      its pathogenesis. 

PMID- 23858402
TI  - Long-term immunogenicity of the influenza vaccine at reduced intradermal and full
      intramuscular doses among healthy young adults.
AB  - PURPOSE: To prepare for vaccine shortages under an influenza pandemic, several
      antigen-sparing strategies have been investigated. This study was aimed to
      evaluate the immunogenicity of influenza vaccine at reduced intradermal and full
      intramuscular dose. MATERIALS AND METHODS: We compared the effect of one-fifth
      and one-half intradermal doses to the full intramuscular dose on immunogenicity
      in healthy young adults, using a commercial influenza vaccine. A hemagglutination
      inhibition assay was used to compare the immunogenicity of the vaccination
      methods. RESULTS: The one-fifth intradermal dose (3 ug hemagglutinin antigen, HA)
      was given to 30 participants, the one-half intradermal dose (7.5 ug HA) was given
      to 30, and the full intramuscular dose (15 ug HA) was given to 32. No significant
      differences among injection routes and dosages were seen for seroprotection rate,
      seroconversion rate, or geometric mean titer (GMT) fold-increase for A/H1N1,
      A/H3N2, and B at around 4 weeks from vaccination. Although GMT for influenza B
      was significantly lower at six months for the one-fifth intradermal vaccination
      compared to the full-dose intramuscular vaccination (32.8 vs. 63.2, p=0.048), all
      three groups met the Evaluation of Medicinal Products (EMA) immunogenicity
      criteria through 1 to 6 months. CONCLUSION: Intradermal administration of a one
      fifth dose of influenza vaccine elicited antibody responses comparable to the
      intradermal one-half dose and a conventional intramuscular vaccination at 1 month
      post-vaccination. The immunogenicity of the one-fifth intradermal dose was
      sufficient to meet the requirement for the EMA criteria at six months after
      influenza vaccination.

PMID- 23858403
TI  - Current status of production and market of human vaccine products in Korea.
AB  - PURPOSE: The goal of this study was to build basic information related to the
      production and market of human vaccine products in Korea, which can be an
      important indicator to provide basic data in practical use. MATERIALS AND
      METHODS: Statistical data were obtained from the Bank of Korea, Korea Health
      Industry Development Institute, Korea Pharmaceutical Traders Association, and
      Korea Pharmaceutical Manufacturers Association. RESULTS: Vaccines are the 10th
      ranked drugs in the classification of whole complete preparated drugs. The
      production output of vaccines in Korea was 392.2 billion KRW in 2011, comprising
      2.83% of complete preparated drug production output (13 trillion 880.8 billion
      KRW) and 2.54% of medical-pharmaceutical product output (15 trillion 440.3
      billion KRW). The market scale of vaccines in Korea was 710 billion KRW in 2011,
      with an annual average growth rate of 11% in the past 6 years, comprising 2% of
      vaccine market in the world. There was also a significant increase in essential
      vaccines and other preventive vaccines in a global scale. CONCLUSION: Vaccines
      have the potential of becoming an emerging attractive industry. Based on the
      current analysis about the production of vaccine products and market scale,
      further development of the vaccine industry is expected in Korea.

PMID- 23858404
TI  - Intranasal immunization with a flagellin-adjuvanted peptide anticancer vaccine
      prevents tumor development by enhancing specific cytotoxic T lymphocyte response
      in a mouse model.
AB  - PURPOSE: Human papillomavirus (HPV) is a significant cause of cervical cancer
      related deaths worldwide. Because HPV is a sexually transmitted mucosal pathogen,
      enhancement of antigen-specific mucosal immune response likely serves good
      strategy for vaccination. However, mucosal vaccines generally do not induce
      strong enough immune responses. Previously we proved that a bacterial flagellin,
      Vibrio vulnificus FlaB, induce strong antigen-specific immune responses by
      stimulating the Toll-like receptor 5. In this study, we tested whether FlaB could
      serve as an effective mucosal adjuvant for a peptide-based HPV preventive cancer
      vaccine. MATERIALS AND METHODS: Mice were intranasally administered with a
      mixture of FlaB and E6/E7 protective peptides in 5-day interval for a total of
      two times. Five-days after the last vaccination, cellular immune responses of the
      vaccinated mice were analyzed. Tumor growth was also observed after a
      subcutaneous implantation of TC-1 cells bearing E6/E7 antigens. RESULTS:
      Intranasal administration of the E6/E7 peptide mixture with FlaB elicited a
      strong antigen-specific cytotoxic T lymphocyte activity and antigen-specific
      interferon-gamma production from splenocytes and cervical lymph node cells.
      Furthermore, FlaB, as a mucosal adjuvant, conferred an excellent protection
      against TC-1 tumor challenge with high survival rates in E6/E7 immunized animals.
      CONCLUSION: These results indicate that FlaB can be a promising mucosal adjuvant
      for nasal HPV vaccine development.

PMID- 23858405
TI  - Efficacy of a commercial live attenuated Lawsonia intracellularis vaccine in a
      large scale field trial in Korea.
AB  - PURPOSE: Porcine proliferative enteropathy (PPE) is known as one of the most
      important risk factors causing economic losses in swine industry worldwide. This
      study was conducted to evaluate the efficacy of a commercial oral attenuated
      Lawsonia intracellularis vaccine (Enterisol Ileitis) against PPE under a
      commercial pig farm condition in Korea. MATERIALS AND METHODS: Thirty two-day-old
      672 piglets were randomly allocated into vaccinated and control groups. All
      piglets in the vaccinated group were inoculated with a commercial attenuated L.
      intracellularis vaccine as following the manufacturer's instruction. Body weights
      of all pigs in both groups were measured on the vaccination day and 6, 14, and 20
      weeks post vaccination and an average daily weight gain (ADWG) was calculated.
      Health status was observed biweekly during the whole trial. RESULTS: The
      vaccinated group showed significantly higher body weight (p<0.05) and ADWG
      (p<0.05) than those of the control group. The vaccinated group had significantly
      reduced impairments in activity, growth, defecation frequency, and stool hardness
      (p<0.05). Additional health benefits and improved weight gain by the vaccination
      produced a 4.2:1 return of investment, and the higher gross margin was $4.80 per
      pig. CONCLUSION: Our finding suggests that the L. intracellularis vaccine program
      has effects on the substantial health and economic benefits in the Korean swine
      industry.

PMID- 23858406
TI  - Varicella outbreak in the patients during group therapy: seroprevalence in a
      healthcare system during breakthrough varicella occurrence.
AB  - PURPOSE: There are different principles regarding varicella vaccination depending
      on social requirements. This study was performed to report a case of breakthrough
      chickenpox outbreak among a group of people in the healthcare center and also
      evaluate the seroprevalence of patients who have been managed with chronic
      neurological diseases in this center. MATERIALS AND METHODS: We included patients
      diagnosed with varicella in April 2009 as an index cases and investigated the
      past history for chickenpox and the varicella-specific IgG. Sixty-two patients
      (children) and 156 healthcare workers who may have had possible contact with the
      index cases were also investigated for. RESULTS: We investigated the
      seroprevalence of 62 patients not affected by the outbreak. The varicella
      vaccination rate in children was 90.3%. Sixty-one point three percent of all
      patients were seropositive and 63.6% of these patients were aged between 12 and
      23 months and 87.5% were aged between 24 and 35 months. Seropositive rate was
      decreased for patients aged between 36 and 59 months while the seropositive
      prevalence has increased for patients over 5 years old. Over 90% of the adults
      investigated were seropositive. IgG seronegative despite vaccination was 32.1%
      (18 persons). CONCLUSION: Breakthrough varicella outbreak can have huge impact in
      healthcare centers with affiliated group housing. We need to investigate
      vaccination status and immunogenicity according to ages and reflect appropriately
      on vaccination policy taking into consideration of social and medical
      requirements in the local area.

PMID- 23858407
TI  - Recommended immunization schedule for children and adolescents in Korea, the
      Korean Pediatric Society, 2013 (The Committee on Infectious Diseases, the Korean
      Pediatric Society).
AB  - This guideline contains the recommended immunization schedule for children and
      adolescents in Korea by the Committee on Infectious Diseases of the Korean
      Pediatric Society, updated in March 2013. It also includes a catch-up
      immunization schedule for children and adolescents who are behind the recommended
      schedule. These schedules are a minor revision of the corresponding parts of
      immunization guideline, 7th edition, of the Korean Pediatric Society, released in
      2012. Tables of this paper are published with quotation approval of immunization
      schedule English version of Committee on Infectious Diseases and Committee on
      Publication of the Korean Pediatric Society. 

PMID- 23858409
TI  - Neocortical interneurons: functional diversity and clinical correlations.

PMID- 23858408
TI  - Epidemiology of stroke and its subtypes in Chinese vs white populations: a
      systematic review.
AB  - OBJECTIVE: We aimed to systematically assess the evidence for differences in the
      incidence of stroke and distribution of its subtypes in Chinese compared with
      white populations. METHODS: We comprehensively sought studies conducted since
      1990 in Chinese populations of 1) first-ever stroke incidence (community-based
      studies only), and 2) pathologic types/subtypes of stroke (hospital- or community
      based studies of first-ever or recurrent strokes). We identified community-based
      studies in white populations from a recent systematic review. For each study, we
      calculated age-standardized stroke incidence and the proportions of each
      pathologic type and ischemic subtype, using random-effects meta-analysis to pool
      proportions of stroke types/subtypes in Chinese and in white populations.
      RESULTS: Age-standardized annual first-ever stroke incidence in community-based
      studies was higher among Chinese than white populations (for ages 45-74 years,
      range 205-584 vs 170-335 per 100,000, respectively). Intracerebral hemorrhage
      accounted for a larger, more variable proportion of strokes in China than Taiwan
      (range 27%-51% vs 17%-28%), in Chinese community-based than hospital-based
      studies (27%-51% vs 17%-30%), and in community-based Chinese than white studies
      (pooled proportion 33% vs 12%). Although the overall proportion of lacunar
      ischemic stroke appeared higher in Chinese than white populations, variable study
      methodologies precluded reliable comparisons. CONCLUSIONS: There is good evidence
      for a slightly higher overall stroke incidence and higher proportion of
      intracerebral hemorrhage in Chinese vs white populations, but no clear evidence
      for different distributions of ischemic stroke subtypes. Studies using
      comparable, population-based case ascertainment and similar classification
      methods are needed to address this.

PMID- 23858410
TI  - Mitochondrial encephalomyopathies--fifty years on: the Robert Wartenberg Lecture.

PMID- 23858412
TI  - Lipoid proteinosis with bilateral amygdalae calcifications, headache, and
      cognitive impairments.

PMID- 23858413
TI  - Demand-supply of neurointerventionalists for endovascular ischemic stroke
      therapy.

PMID- 23858411
TI  - APOE genotype and MRI markers of cerebrovascular disease: systematic review and
      meta-analysis.
AB  - OBJECTIVE: We aimed to examine the association of APOE epsilon genotype with MRI
      markers of cerebrovascular disease (CVD): white matter hyperintensities, brain
      infarcts, and cerebral microbleeds. METHODS: We performed a systematic review and
      meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed
      from 1966 to June 2012 (n = 29,965). This included unpublished data from 3
      population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and
      Ageing Study. When necessary, authors were contacted to provide effect estimates
      for the meta-analysis. RESULTS: APOE epsilon4 carrier status and APOE epsilon44
      genotype were associated with increasing white matter hyperintensity burden
      (sample size-weighted z score meta-analysis [meta]-p = 0.0034 and 0.0030) and
      presence of cerebral microbleeds (meta odds ratio [OR] = 1.24, 95% confidence
      interval [CI] [1.07, 1.43], p = 0.004, and 1.87 [1.26, 2.78], p = 0.002),
      especially lobar. APOE epsilon2 carrier status was associated with increasing
      white matter hyperintensity load (z score meta-p = 0.00053) and risk of brain
      infarct (meta OR = 1.41[1.09, 1.81], p = 0.008). CONCLUSIONS: APOE epsilon4 and
      APOE epsilon2 were associated with increasing burden in MRI markers for both
      hemorrhagic and ischemic CVD. While the association of APOE epsilon4 with an
      increased burden of CVD could be partly contributing to the relationship between
      APOE epsilon4 and AD, APOE epsilon2 was associated with MRI markers of CVD in the
      opposite direction compared to AD.

PMID- 23858414
TI  - Varicella-zoster virus encephalitis and vasculopathy in a patient treated with
      fingolimod.

PMID- 23858415
TI  - Child Neurology: Pediatric seizures with hyaline astrocytic inclusions.

PMID- 23858416
TI  - Teaching NeuroImages: Multiple giant intracranial aneurysms in Klippel-Trenaunay
      syndrome.

PMID- 23858417
TI  - Teaching neuroimages: ataxia and diabetes insipidus.

PMID- 23858418
TI  - The relationship between parents' and children's television viewing.
AB  - OBJECTIVE: To examine the effect of parental television viewing on children's
      television viewing compared with traditional predictors such as household
      television access, parental rules, and demographic characteristics of the child,
      parent, and household. METHODS: An online survey using national samples of 1550
      parents with children in 3 age groups (children <= 5 years, children aged 6-11
      years, and adolescents aged 12-17 years), weighted to be representative of US
      parents with children in each age group. Adolescents (n = 629) of participating
      parents were also surveyed. RESULTS: Parent television time is associated with
      child television time and had a stronger relationship to child time than access
      to television in the home or the child's bedroom, as well as parental rules about
      television viewing and coviewing. This pattern persisted across all age groups of
      children. CONCLUSIONS: Educating parents about the relationship between their own
      and their child's viewing may be a useful strategy for interventions that aim to
      reduce children's excessive television viewing. Additionally, health
      professionals can engage parents in a discussion about how family television time
      is associated with increased television time for children.

PMID- 23858419
TI  - Preventing dental caries in children <5 years: systematic review updating USPSTF
      recommendation.
AB  - BACKGROUND AND OBJECTIVE: Screening and preventive interventions by primary care
      providers could improve outcomes related to early childhood caries. The objective
      of this study was to update the 2004 US Preventive Services Task Force systematic
      review on prevention of caries in children younger than 5 years of age. METHODS:
      Searching Medline and the Cochrane Library (through March 2013) and reference
      lists, we included trials and controlled observational studies on the
      effectiveness and harms of screening and treatments. One author extracted study
      characteristics and results, which were checked for accuracy by a second author.
      Two authors independently assessed study quality. RESULTS: No study evaluated
      effects of screening by primary care providers on clinical outcomes. One good
      quality cohort study found pediatrician examination associated with a sensitivity
      of 0.76 for identifying a child with cavities. No new trials evaluated oral
      fluoride supplementation. Three new randomized trials were consistent with
      previous studies in finding fluoride varnish more effective than no varnish
      (reduction in caries increment 18% to 59%). Three trials of xylitol were
      inconclusive regarding effects on caries. New observational studies were
      consistent with previous evidence showing an association between early childhood
      fluoride use and enamel fluorosis. Evidence on the accuracy of risk prediction
      instruments in primary care settings is not available. CONCLUSIONS: There is no
      direct evidence that screening by primary care clinicians reduces early childhood
      caries. Evidence previously reviewed by the US Preventive Services Task Force
      found oral fluoride supplementation effective at reducing caries incidence, and
      new evidence supports the effectiveness of fluoride varnish in higher-risk
      children.

PMID- 23858420
TI  - Characteristics of pain in children and youth with cerebral palsy.
AB  - OBJECTIVES: Pain in children with cerebral palsy (CP) is underrecognized,
      undertreated, and negatively affects quality of life. Communication challenges
      and multiple pain etiologies complicate diagnosis and treatment. The primary
      objectives of this study were to determine the impact of pain on activities and
      to identify the common physician-identified causes of pain in children and youth
      ages 3 to 19 years across all levels of severity of CP. METHODS: The study design
      was cross-sectional, whereby children/youth aged 3 to 19 years and their families
      were consecutively recruited. The primary caregivers were asked to complete a one
      time questionnaire, including the Health Utilities Index 3 pain subset, about the
      presence and characteristics of pain. The treating physician was asked to
      identify the presence of pain and provide a clinical diagnosis for the pain, if
      applicable. RESULTS: The response rate was 92%. Of 252 participants, 54.8%
      reported some pain on the Health Utilities Index 3, with 24.4% of the caregivers
      reporting that their child experienced pain that affected some level of
      activities in the preceding 2 weeks. Physicians reported pain in 38.7% and
      identified hip dislocation/subluxation, dystonia, and constipation as the most
      frequent causes of pain. CONCLUSIONS: One-quarter of our sample experienced pain
      that limited activities and participation. Clinicians should be aware that hip
      subluxation/dislocation and dystonia were the most common causes of pain in
      children/youth with CP in this study. Potential causes of pain should be
      identified and addressed early to mitigate the negative impact of pain on quality
      of life.

PMID- 23858421
TI  - Is there an association between physical punishment in childhood and physical
      health in adulthood?

PMID- 23858422
TI  - Clonal cytophagic histiocytic panniculitis in children may be cured by
      cyclosporine A.
AB  - Cytophagic histiocytic panniculitis (CHP) is a rare panniculitis in childhood,
      associated either with nonmalignant conditions or with subcutaneous panniculitis
      like T-cell lymphoma (SPTCL), and often also associated with macrophage
      activation syndrome (MAS). Discriminating between these 2 conditions is
      therapeutically important because nonmalignant CHP often improves under
      cyclosporine and prednisone, whereas most cases of SPLT may be best treated with
      more aggressive therapy. We report the cases of a 6-month-old boy and a 16-month
      old girl who, after viral infection, developed multiple infiltrating skin nodules
      on the limbs and face, associated with MAS. Histopathologic findings for skin
      biopsy specimens revealed CHP associated with heavily cellular lobular
      panniculitis. Hemophagocytosis and immunohistochemical staining features were
      consistent with typical characteristics of in situ MAS in adipose tissue: the
      lymphocytes were mostly TCD8+ cells with an activated phenotype (human leukocyte
      antigen (HLA) -DR+) and expressed interferon-gamma; CD68+ macrophages expressed
      tumor necrosis factor-alpha and interleukin-6. A monoclonal rearrangement of the
      T-cell receptor gamma gene was present in skin tissue but not in peripheral blood
      or bone marrow lymphocytes. Cyclosporine A treatment resulted in the complete
      remission of cutaneous and systemic manifestations in both patients for 66 and 29
      months, respectively. This report suggests that the diagnosis of a reactive T
      cell lymphoproliferation should be the treatment of choice in young children with
      severe CHP, even if there is a SPTCL-like aspect with an in situ T-cell
      clonality. It also suggests that CSA is the optimal treatment of this condition
      and postulates the possible pathologic process underlying this efficacy. 

PMID- 23858423
TI  - Randomized controlled trial of a car safety seat insert to reduce hypoxia in term
      infants.
AB  - OBJECTIVE: To test the hypothesis that a foam plastic insert that allows the
      infant head to rest in a neutral position in sleep may prevent obstruction of the
      upper airway and thus reduce episodes of reduced oxygenation in term infants in
      car seats. METHODS: Healthy full-term babies were randomized to be studied during
      sleep while restrained in an infant car safety seat either with or without the
      insert, with continuous polysomnographic recordings with sleep video. RESULTS:
      Seventy-eight infants (39 in each group) had polysomnogram recordings at a mean
      of 8 days of age. Both groups showed a small fall in mean hemoglobin oxygen
      saturation (SpO2) over the first hour of sleep. There was no difference between
      insert and no insert in the rate of moderate desaturations (a fall in SpO2 >= 4%
      lasting for >= 10 seconds, mean +/- SEM, 17.0 +/- 1.5 vs 17.2 +/- 1.5/hour), or
      mean SpO2 during sleep. The insert was associated with a significant reduction in
      the rate of obstructive apnea (0.3 +/- 0.1 vs 0.9 +/- 1.5/hour, P < .03), the
      severity of desaturation events (minimum SpO2 82% +/- 1% vs 74% +/- 2%, P <
      .001), and time with SpO2 <85% (0.6% +/- 0.3% vs 1.8% +/- 1.4%, P = .03).
      CONCLUSIONS: In full-term newborn infants, a car seat insert that helps the head
      to lie in a neutral position was associated with reduced severity of desaturation
      events but not the overall rate of moderate desaturations.

PMID- 23858424
TI  - The ONE step initiative: quality improvement in a pediatric clinic for secondhand
      smoke reduction.
AB  - BACKGROUND AND OBJECTIVE: Although comprehensive smoking counseling to limit
      secondhand smoke (SHS) is widely endorsed, it is often not done. Published
      evaluations of brief and practical systems that improve screening and counseling
      to reduce SHS are limited. Our objective was to determine if a quality
      improvement activity around smoking counseling leads to changes in (1) medical
      assistant and pediatric provider assessment of smoking history and (2) smoking or
      other behaviors affecting children's SHS exposure. METHODS: In a large urban
      teaching clinic we assessed the ONE Step intervention, which included the
      following: (1) "Ask" (medical assistant asking whether caregivers smoke); (2)
      "Advise" (providers advising smoking outside and quitting if ready); (3) "Refer"
      (providers referring to the Colorado telephone QuitLine); and (4) electronic
      medical record prompts and required documentation regarding smoking. Medical
      assistant and provider assessments of smoking were evaluated with a chart review
      by using a pre-/posttest design. Caregiver behavior change was evaluated with a
      time-series survey that included assessment at baseline and follow-up via
      telephone at 6 and 12 months from study entry. RESULTS: ONE Step was associated
      with a statistically significant increase in Ask, Advise, and Refer
      documentation. Caregiver surveys showed that 97% found discussions of SHS with
      providers acceptable. Six- and 12-month follow-ups, respectively, showed that 14%
      and 13% of smokers reported quitting and that 63% and 70% of current smokers
      reported reduced SHS exposure. CONCLUSIONS: ONE Step was feasible to deliver in a
      busy outpatient setting, acceptable to families, and appears to have resulted in
      decreased exposure to SHS in our pediatric population.

PMID- 23858425
TI  - Results from the New Jersey statewide critical congenital heart defects screening
      program.
AB  - BACKGROUND AND OBJECTIVE: New Jersey was the first state to implement
      legislatively mandated newborn pulse oximetry screening (POxS) in all licensed
      birthing facilities to detect critical congenital heart defects (CCHDs). The
      objective of this report was to evaluate implementation of New Jersey's statewide
      POxS mandate. METHODS: A 2-pronged approach was used to collect data on infants
      screened in all New Jersey birthing facilities from August 31, 2011, through May
      31, 2012. Aggregate screening results were submitted by each birthing facility.
      Data on failed screens and clinical characteristics of those newborns were
      reported to the New Jersey Birth Defects Registry (NJBDR). Three indicators were
      used to distinguish the added value of mandated POxS from standard clinical care:
      prenatal congenital heart defect diagnosis, cardiology consultation or
      echocardiogram indicated or performed before PoxS, or clinical findings at the
      time of POxS warranting a pulse oximetry measurement. RESULTS: Of 75,324 live
      births in licensed New Jersey birthing facilities, 73,320 were eligible for
      screening, of which 99% were screened. Forty-nine infants with failed POxS were
      reported to the NJBDR, 30 of whom had diagnostic evaluations solely attributable
      to the mandated screening. Three of the 30 infants had previously unsuspected
      CCHDs and 17 had other diagnoses or non-CCHD echocardiogram findings.
      CONCLUSIONS: In the first 9 months after implementation, New Jersey achieved a
      high statewide screening rate and established surveillance mechanisms to evaluate
      the unique contribution of POxS. The screening mandate identified 3 infants with
      previously unsuspected CCHDs that otherwise might have resulted in significant
      morbidity and mortality and also identified other significant secondary targets
      such as sepsis and pneumonia.

PMID- 23858426
TI  - Obstetric and neonatal care practices for infants 501 to 1500 g from 2000 to
      2009.
AB  - OBJECTIVE: To identify changes in clinical practices for infants with birth
      weights of 501 to 1500 g born from 2000 to 2009. METHODS: We used prospectively
      collected registry data for 355,806 infants born from 2000 to 2009 and cared for
      at 669 North American hospitals in the Vermont Oxford Network. Main outcome
      measures included obstetric and neonatal practices, including cesarean delivery,
      antenatal steroids, delivery room interventions, respiratory practices,
      neuroimaging, retinal exams, and feeding at discharge. RESULTS: Significant
      changes in many obstetric, delivery room, and neonatal practices occurred from
      2000 to 2009. Use of surfactant treatment in the delivery room increased overall
      (adjusted difference [AD] 17.0%; 95% confidence interval [CI] 16.4% to 17.6%), as
      did less-invasive methods of respiratory support, such as nasal continuous
      positive airway pressure (AD 9.9%; 95% CI 9.1% to 10.6%). Use of any ventilation
      (AD -7.5%; 95% CI -8.0% to -6.9%) and steroids for chronic lung disease (AD 
      15.3%; 95% CI -15.8% to -14.8%) decreased significantly overall. Most of the
      changes in respiratory care were observed within each of 4 birth weight strata
      (501-750 g, 751-1000 g, 1001-1250 g, 1251-1500 g). CONCLUSIONS: Many obstetric
      and neonatal care practices used in the management of infants 501 to 1500 g
      changed between 2000 and 2009. In particular, less-invasive approaches to
      respiratory support increased.

PMID- 23858427
TI  - Estimating overweight risk in childhood from predictors during infancy.
AB  - OBJECTIVE: The aim of this study was to develop and validate a risk score
      algorithm for childhood overweight based on a prediction model in infants.
      METHODS: Analysis was conducted by using the UK Millennium Cohort Study. The
      cohort was divided randomly by using 80% of the sample for derivation of the risk
      algorithm and 20% of the sample for validation. Stepwise logistic regression
      determined a prediction model for childhood overweight at 3 years defined by the
      International Obesity Task Force criteria. Predictive metrics R(2), area under
      the receiver operating curve (AUROC), sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) were calculated.
      RESULTS: Seven predictors were found to be significantly associated with
      overweight at 3 years in a mutually adjusted predictor model: gender, birth
      weight, weight gain, maternal prepregnancy BMI, paternal BMI, maternal smoking in
      pregnancy, and breastfeeding status. Risk scores ranged from 0 to 59
      corresponding to a predicted risk from 4.1% to 73.8%. The model revealed
      moderately good predictive ability in both the derivation cohort (R(2) = 0.92,
      AUROC = 0.721, sensitivity = 0.699, specificity = 0.679, PPV = 38%, NPV = 87%)
      and validation cohort (R(2) = 0.84, AUROC = 0.755, sensitivity = 0.769,
      specificity = 0.665, PPV = 37%, NPV = 89%). CONCLUSIONS: Using a prediction
      algorithm to identify at-risk infants could reduce levels of child overweight and
      obesity by enabling health professionals to target prevention more effectively.
      Further research needs to evaluate the clinical validity, feasibility, and
      acceptability of communicating this risk.

PMID- 23858428
TI  - Harsh physical punishment in childhood and adult physical health.
AB  - BACKGROUND: The use of physical punishment is controversial. No studies have
      comprehensively examined the relationship between physical punishment and several
      physical health conditions in a nationally representative sample. The current
      study investigated possible associations between harsh physical punishment (ie,
      pushing, grabbing, shoving, slapping, and hitting) in the absence of more severe
      child maltreatment (ie, physical abuse, sexual abuse, emotional abuse, physical
      neglect, emotional neglect, and exposure to intimate partner violence) and
      several physical health conditions. METHODS: Data were from the National
      Epidemiologic Survey on Alcohol and Related Conditions collected in 2004 and 2005
      (n = 34,226 in the current analysis). The survey was conducted with a
      representative US adult population sample (20 years or older). Eight past year
      physical health condition categories were assessed. Models were adjusted for
      sociodemographic variables, family history of dysfunction, and Axis I and II
      mental disorders. RESULTS: Harsh physical punishment was associated with higher
      odds of cardiovascular disease (borderline significance), arthritis, and obesity
      after adjusting for sociodemographic variables, family history of dysfunction,
      and Axis I and II mental disorders (adjusted odds ratios ranged from 1.20 to
      1.30). CONCLUSIONS: Harsh physical punishment in the absence of child
      maltreatment is associated with some physical health conditions in a general
      population sample. These findings inform the ongoing debate around the use of
      physical punishment and provide evidence that harsh physical punishment
      independent of child maltreatment is associated with a higher likelihood of
      physical health conditions.

PMID- 23858429
TI  - Diagnosing the learner in difficulty.

PMID- 23858430
TI  - Transcriptional dynamics of two seed compartments with opposing roles in
      Arabidopsis seed germination.
AB  - Seed germination is a critical stage in the plant life cycle and the first step
      toward successful plant establishment. Therefore, understanding germination is of
      important ecological and agronomical relevance. Previous research revealed that
      different seed compartments (testa, endosperm, and embryo) control germination,
      but little is known about the underlying spatial and temporal transcriptome
      changes that lead to seed germination. We analyzed genome-wide expression in
      germinating Arabidopsis (Arabidopsis thaliana) seeds with both temporal and
      spatial detail and provide Web-accessible visualizations of the data reported
      (vseed.nottingham.ac.uk). We show the potential of this high-resolution data set
      for the construction of meaningful coexpression networks, which provide insight
      into the genetic control of germination. The data set reveals two transcriptional
      phases during germination that are separated by testa rupture. The first phase is
      marked by large transcriptome changes as the seed switches from a dry, quiescent
      state to a hydrated and active state. At the end of this first transcriptional
      phase, the number of differentially expressed genes between consecutive time
      points drops. This increases again at testa rupture, the start of the second
      transcriptional phase. Transcriptome data indicate a role for mechano-induced
      signaling at this stage and subsequently highlight the fates of the endosperm and
      radicle: senescence and growth, respectively. Finally, using a
      phylotranscriptomic approach, we show that expression levels of evolutionarily
      young genes drop during the first transcriptional phase and increase during the
      second phase. Evolutionarily old genes show an opposite pattern, suggesting a
      more conserved transcriptome prior to the completion of germination. 

PMID- 23858431
TI  - Reducing spread in climate model projections of a September ice-free Arctic.
AB  - This paper addresses the specter of a September ice-free Arctic in the 21st
      century using newly available simulations from the Coupled Model Intercomparison
      Project Phase 5 (CMIP5). We find that large spread in the projected timing of the
      September ice-free Arctic in 30 CMIP5 models is associated at least as much with
      different atmospheric model components as with initial conditions. Here we reduce
      the spread in the timing of an ice-free state using two different approaches for
      the 30 CMIP5 models: (i) model selection based on the ability to reproduce the
      observed sea ice climatology and variability since 1979 and (ii) constrained
      estimation based on the strong and persistent relationship between present and
      future sea ice conditions. Results from the two approaches show good agreement.
      Under a high-emission scenario both approaches project that September ice extent
      will drop to ~1.7 million km(2) in the mid 2040s and reach the ice-free state
      (defined as 1 million km(2)) in 2054-2058. Under a medium-mitigation scenario,
      both approaches project a decrease to ~1.7 million km(2) in the early 2060s,
      followed by a leveling off in the ice extent. 

PMID- 23858433
TI  - Digital instability of a confined elastic meniscus.
AB  - Thin soft elastic layers serving as joints between relatively rigid bodies may
      function as sealants, thermal, electrical, or mechanical insulators, bearings, or
      adhesives. When such a joint is stressed, even though perfect adhesion is
      maintained, the exposed free meniscus in the thin elastic layer becomes unstable,
      leading to the formation of spatially periodic digits of air that invade the
      elastic layer, reminiscent of viscous fingering in a thin fluid layer. However,
      the elastic instability is reversible and rate-independent, disappearing when the
      joint is unstressed. We use theory, experiments, and numerical simulations to
      show that the transition to the digital state is sudden (first-order), the
      wavelength and amplitude of the fingers are proportional to the thickness of the
      elastic layer, and the required separation to trigger the instability is
      inversely proportional to the in-plane dimension of the layer. Our study reveals
      the energetic origin of this instability and has implications for the strength of
      polymeric adhesives; it also suggests a method for patterning thin films
      reversibly with any arrangement of localized fingers in a digital elastic memory,
      which we confirm experimentally. 

PMID- 23858432
TI  - Self-organized vascular networks from human pluripotent stem cells in a synthetic
      matrix.
AB  - The success of tissue regenerative therapies is contingent on functional and
      multicellular vasculature within the redeveloping tissue. Although endothelial
      cells (ECs), which compose the vasculature's inner lining, are intrinsically able
      to form nascent networks, these structures regress without the recruitment of
      pericytes, supporting cells that surround microvessel endothelium. Reconstruction
      of typical in vivo microvascular architecture traditionally has been done using
      distinct cell sources of ECs and pericytes within naturally occurring matrices;
      however, the limited sources of clinically relevant human cells and the inherent
      chemical and physical properties of natural materials hamper the translational
      potential of these approaches. Here we derived a bicellular vascular population
      from human pluripotent stem cells (hPSCs) that undergoes morphogenesis and
      assembly in a synthetic matrix. We found that hPSCs can be induced to
      codifferentiate into early vascular cells (EVCs) in a clinically relevant
      strategy amenable to multiple hPSC lines. These EVCs can mature into ECs and
      pericytes, and can self-organize to form microvascular networks in an engineered
      matrix. These engineered human vascular networks survive implantation, integrate
      with the host vasculature, and establish blood flow. This integrated approach, in
      which a derived bicellular population is exploited for its intrinsic self
      assembly capability to create microvasculature in a deliverable matrix, has vast
      ramifications for vascular construction and regenerative medicine. 

PMID- 23858434
TI  - QnAs with Arthur Beaudet.

PMID- 23858435
TI  - Physical evidence of predatory behavior in Tyrannosaurus rex.
AB  - Feeding strategies of the large theropod, Tyrannosaurus rex, either as a predator
      or a scavenger, have been a topic of debate previously compromised by lack of
      definitive physical evidence. Tooth drag and bone puncture marks have been
      documented on suggested prey items, but are often difficult to attribute to a
      specific theropod. Further, postmortem damage cannot be distinguished from
      intravital occurrences, unless evidence of healing is present. Here we report
      definitive evidence of predation by T. rex: a tooth crown embedded in a
      hadrosaurid caudal centrum, surrounded by healed bone growth. This indicates that
      the prey escaped and lived for some time after the injury, providing direct
      evidence of predatory behavior by T. rex. The two traumatically fused hadrosaur
      vertebrae partially enclosing a T. rex tooth were discovered in the Hell Creek
      Formation of South Dakota. 

PMID- 23858436
TI  - Illusory ownership of a virtual child body causes overestimation of object sizes
      and implicit attitude changes.
AB  - An illusory sensation of ownership over a surrogate limb or whole body can be
      induced through specific forms of multisensory stimulation, such as synchronous
      visuotactile tapping on the hidden real and visible rubber hand in the rubber
      hand illusion. Such methods have been used to induce ownership over a manikin and
      a virtual body that substitute the real body, as seen from first-person
      perspective, through a head-mounted display. However, the perceptual and
      behavioral consequences of such transformed body ownership have hardly been
      explored. In Exp. 1, immersive virtual reality was used to embody 30 adults as a
      4-y-old child (condition C), and as an adult body scaled to the same height as
      the child (condition A), experienced from the first-person perspective, and with
      virtual and real body movements synchronized. The result was a strong body
      ownership illusion equally for C and A. Moreover there was an overestimation of
      the sizes of objects compared with a nonembodied baseline, which was
      significantly greater for C compared with A. An implicit association test showed
      that C resulted in significantly faster reaction times for the classification of
      self with child-like compared with adult-like attributes. Exp. 2 with an
      additional 16 participants extinguished the ownership illusion by using
      visuomotor asynchrony, with all else equal. The size-estimation and implicit
      association test differences between C and A were also extinguished. We conclude
      that there are perceptual and probably behavioral correlates of body-ownership
      illusions that occur as a function of the type of body in which embodiment
      occurs. 

PMID- 23858437
TI  - Neural crest and Schwann cell progenitor-derived melanocytes are two spatially
      segregated populations similarly regulated by Foxd3.
AB  - Skin melanocytes arise from two sources: either directly from neural crest
      progenitors or indirectly from neural crest-derived Schwann cell precursors after
      colonization of peripheral nerves. The relationship between these two melanocyte
      populations and the factors controlling their specification remains poorly
      understood. Direct lineage tracing reveals that neural crest and Schwann cell
      progenitor-derived melanocytes are differentially restricted to the epaxial and
      hypaxial body domains, respectively. Furthermore, although both populations are
      initially part of the Foxd3 lineage, hypaxial melanocytes lose Foxd3 at late
      stages upon separation from the nerve, whereas we recently found that epaxial
      melanocytes segregate earlier from Foxd3-positive neural progenitors while still
      residing in the dorsal neural tube. Gain- and loss-of-function experiments in
      avians and mice, respectively, reveal that Foxd3 is both sufficient and necessary
      for regulating the balance between melanocyte and Schwann cell development. In
      addition, Foxd3 is also sufficient to regulate the switch between neuronal and
      glial fates in sensory ganglia. Together, we propose that differential fate
      acquisition of neural crest-derived cells depends on their progressive
      segregation from the Foxd3-positive lineage. 

PMID- 23858438
TI  - Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic
      in vitro.
AB  - Thalidomide and its analog, Lenalidomide, are in current use clinically for
      treatment of multiple myeloma, complications of leprosy and cancers. An
      additional analog, Pomalidomide, has recently been licensed for treatment of
      multiple myeloma, and is purported to be clinically more potent than either
      Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos
      together with in vitro assays we have determined the relative anti-inflammatory
      activity of each compound. We demonstrate that in vivo embryonic assays
      Pomalidomide is a significantly more potent anti-inflammatory agent than either
      Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and
      Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known
      detrimental effects of Thalidomide. We found that Pomalidomide, displays a high
      degree of cell specificity, and has no detectable teratogenic, antiangiogenic or
      neurotoxic effects at potent anti-inflammatory concentrations. This is in marked
      contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood
      vessels, nerves, and embryonic development at anti-inflammatory concentrations.
      This work has implications for Pomalidomide as a treatment for conditions
      Thalidomide and Lenalidomide treat currently. 

PMID- 23858440
TI  - Species-fragmented area relationship.
AB  - The species-area relationship (SAR) gives a quantitative description of the
      increasing number of species in a community with increasing area of habitat. In
      conservation, SARs have been used to predict the number of extinctions when the
      area of habitat is reduced. Such predictions are most needed for landscapes
      rather than for individual habitat fragments, but SAR-based predictions of
      extinctions for landscapes with highly fragmented habitat are likely to be biased
      because SAR assumes contiguous habitat. In reality, habitat loss is typically
      accompanied by habitat fragmentation. To quantify the effect of fragmentation in
      addition to the effect of habitat loss on the number of species, we extend the
      power-law SAR to the species-fragmented area relationship. This model unites the
      single-species metapopulation theory with the multispecies SAR for communities.
      We demonstrate with a realistic simulation model and with empirical data for
      forest-inhabiting subtropical birds that the species-fragmented area relationship
      gives a far superior prediction than SAR of the number of species in fragmented
      landscapes. The results demonstrate that for communities of species that are not
      well adapted to live in fragmented landscapes, the conventional SAR
      underestimates the number of extinctions for landscapes in which little habitat
      remains and it is highly fragmented. 

PMID- 23858439
TI  - Twelve previously unknown phage genera are ubiquitous in global oceans.
AB  - Viruses are fundamental to ecosystems ranging from oceans to humans, yet our
      ability to study them is bottlenecked by the lack of ecologically relevant
      isolates, resulting in "unknowns" dominating culture-independent surveys. Here we
      present genomes from 31 phages infecting multiple strains of the aquatic
      bacterium Cellulophaga baltica (Bacteroidetes) to provide data for an
      underrepresented and environmentally abundant bacterial lineage. Comparative
      genomics delineated 12 phage groups that (i) each represent a new genus, and (ii)
      represent one novel and four well-known viral families. This diversity contrasts
      the few well-studied marine phage systems, but parallels the diversity of phages
      infecting human-associated bacteria. Although all 12 Cellulophaga phages
      represent new genera, the podoviruses and icosahedral, nontailed ssDNA phages
      were exceptional, with genomes up to twice as large as those previously observed
      for each phage type. Structural novelty was also substantial, requiring
      experimental phage proteomics to identify 83% of the structural proteins. The
      presence of uncommon nucleotide metabolism genes in four genera likely
      underscores the importance of scavenging nutrient-rich molecules as previously
      seen for phages in marine environments. Metagenomic recruitment analyses suggest
      that these particular Cellulophaga phages are rare and may represent a first
      glimpse into the phage side of the rare biosphere. However, these analyses also
      revealed that these phage genera are widespread, occurring in 94% of 137
      investigated metagenomes. Together, this diverse and novel collection of phages
      identifies a small but ubiquitous fraction of unknown marine viral diversity and
      provides numerous environmentally relevant phage-host systems for experimental
      hypothesis testing. 

PMID- 23858441
TI  - Single-dose vaccine against tick-borne encephalitis.
AB  - Tick-borne encephalitis (TBE) virus is the most important human pathogen
      transmitted by ticks in Eurasia. Inactivated vaccines are available but require
      multiple doses and frequent boosters to induce and maintain immunity. Thus far,
      the goal of developing a safe, live attenuated vaccine effective after a single
      dose has remained elusive. Here we used a replication-defective (single-cycle)
      flavivirus platform, RepliVax, to generate a safe, single-dose TBE vaccine.
      Several RepliVax-TBE candidates attenuated by a deletion in the capsid gene were
      constructed using different flavivirus backbones containing the envelope genes of
      TBE virus. RepliVax-TBE based on a West Nile virus backbone (RV-WN/TBE) grew more
      efficiently in helper cells than candidates based on Langat E5, TBE, and yellow
      fever 17D backbones, and was found to be highly immunogenic and efficacious in
      mice. Live chimeric yellow fever 17D/TBE, Dengue 2/TBE, and Langat E5/TBE
      candidates were also constructed but were found to be underattenuated. RV-WN/TBE
      was demonstrated to be highly immunogenic in Rhesus macaques after a single dose,
      inducing a significantly more durable humoral immune response compared with three
      doses of a licensed, adjuvanted human inactivated vaccine. Its immunogenicity was
      not significantly affected by preexisting immunity against WN. Immunized monkeys
      were protected from a stringent surrogate challenge. These results support the
      identification of a single-cycle TBE vaccine with a superior product profile to
      existing inactivated vaccines, which could lead to improved vaccine coverage and
      control of the disease. 

PMID- 23858443
TI  - The multimillennial sea-level commitment of global warming.
AB  - Global mean sea level has been steadily rising over the last century, is
      projected to increase by the end of this century, and will continue to rise
      beyond the year 2100 unless the current global mean temperature trend is
      reversed. Inertia in the climate and global carbon system, however, causes the
      global mean temperature to decline slowly even after greenhouse gas emissions
      have ceased, raising the question of how much sea-level commitment is expected
      for different levels of global mean temperature increase above preindustrial
      levels. Although sea-level rise over the last century has been dominated by ocean
      warming and loss of glaciers, the sensitivity suggested from records of past sea
      levels indicates important contributions should also be expected from the
      Greenland and Antarctic Ice Sheets. Uncertainties in the paleo-reconstructions,
      however, necessitate additional strategies to better constrain the sea-level
      commitment. Here we combine paleo-evidence with simulations from physical models
      to estimate the future sea-level commitment on a multimillennial time scale and
      compute associated regional sea-level patterns. Oceanic thermal expansion and the
      Antarctic Ice Sheet contribute quasi-linearly, with 0.4 m  degrees C(-1) and 1.2
      m  degrees C(-1) of warming, respectively. The saturation of the contribution
      from glaciers is overcompensated by the nonlinear response of the Greenland Ice
      Sheet. As a consequence we are committed to a sea-level rise of approximately 2.3
      m  degrees C(-1) within the next 2,000 y. Considering the lifetime of
      anthropogenic greenhouse gases, this imposes the need for fundamental adaptation
      strategies on multicentennial time scales. 

PMID- 23858442
TI  - Cranial irradiation compromises neuronal architecture in the hippocampus.
AB  - Cranial irradiation is used routinely for the treatment of nearly all brain
      tumors, but may lead to progressive and debilitating impairments of cognitive
      function. Changes in synaptic plasticity underlie many neurodegenerative
      conditions that correlate to specific structural alterations in neurons that are
      believed to be morphologic determinants of learning and memory. To determine
      whether changes in dendritic architecture might underlie the neurocognitive
      sequelae found after irradiation, we investigated the impact of cranial
      irradiation (1 and 10 Gy) on a range of micromorphometric parameters in mice 10
      and 30 d following exposure. Our data revealed significant reductions in
      dendritic complexity, where dendritic branching, length, and area were routinely
      reduced (>50%) in a dose-dependent manner. At these same doses and times we found
      significant reductions in the number (20-35%) and density (40-70%) of dendritic
      spines on hippocampal neurons of the dentate gyrus. Interestingly, immature
      filopodia showed the greatest sensitivity to irradiation compared with more
      mature spine morphologies, with reductions of 43% and 73% found 30 d after 1 and
      10 Gy, respectively. Analysis of granule-cell neurons spanning the subfields of
      the dentate gyrus revealed significant reductions in synaptophysin expression at
      presynaptic sites in the dentate hilus, and significant increases in postsynaptic
      density protein (PSD-95) were found along dendrites in the granule cell and
      molecular layers. These findings are unique in demonstrating dose-responsive
      changes in dendritic complexity, synaptic protein levels, spine density and
      morphology, alterations induced in hippocampal neurons by irradiation that
      persist for at least 1 mo, and that resemble similar types of changes found in
      many neurodegenerative conditions. 

PMID- 23858444
TI  - Gene expression profiles in febrile children with defined viral and bacterial
      infection.
AB  - Viral infections are common causes of fever without an apparent source in young
      children. Despite absence of bacterial infection, many febrile children are
      treated with antibiotics. Virus and bacteria interact with different pattern
      recognition receptors in circulating blood leukocytes, triggering specific host
      transcriptional programs mediating immune response. Therefore, unique
      transcriptional signatures may be defined that discriminate viral from bacterial
      causes of fever without an apparent source. Gene expression microarray analyses
      were conducted on blood samples from 30 febrile children positive for adenovirus,
      human herpesvirus 6, or enterovirus infection or with acute bacterial infection
      and 22 afebrile controls. Blood leukocyte transcriptional profiles clearly
      distinguished virus-positive febrile children from both virus-negative afebrile
      controls and afebrile children with the same viruses present in the febrile
      children. Virus-specific gene expression profiles could be defined. The IFN
      signaling pathway was uniquely activated in febrile children with viral
      infection, whereas the integrin signaling pathway was uniquely activated in
      children with bacterial infection. Transcriptional profiles classified febrile
      children with viral or bacterial infection with better accuracy than white blood
      cell count in the blood. Similarly accurate classification was shown with data
      from an independent study using different microarray platforms. Our results
      support the paradigm of using host response to define the etiology of childhood
      infections. This approach could be an important supplement to highly sensitive
      tests that detect the presence of a possible pathogen but do not address its
      pathogenic role in the patient being evaluated. 

PMID- 23858445
TI  - Reptin/Ruvbl2 is a Lrrc6/Seahorse interactor essential for cilia motility.
AB  - Primary ciliary dyskinesia (PCD) is an autosomal recessive disease caused by
      defective cilia motility. The identified PCD genes account for about half of PCD
      incidences and the underlying mechanisms remain poorly understood. We demonstrate
      that Reptin/Ruvbl2, a protein known to be involved in epigenetic and
      transcriptional regulation, is essential for cilia motility in zebrafish. We
      further show that Reptin directly interacts with the PCD protein Lrrc6/Seahorse
      and this interaction is critical for the in vivo function of Lrrc6/Seahorse in
      zebrafish. Moreover, whereas the expression levels of multiple dynein arm
      components remain unchanged or become elevated, the density of axonemal dynein
      arms is reduced in reptin(hi2394) mutants. Furthermore, Reptin is highly enriched
      in the cytosol and colocalizes with Lrrc6/Seahorse. Combined, these results
      suggest that the Reptin-Lrrc6/Seahorse complex is involved in dynein arm
      formation. We also show that although the DNA damage response is induced in
      reptin(hi2394) mutants, it remains unchanged in cilia biogenesis mutants and
      lrrc6/seahorse mutants, suggesting that increased DNA damage response is not
      intrinsic to ciliary defects and that in vertebrate development, Reptin functions
      in multiple processes, both cilia specific and cilia independent. 

PMID- 23858447
TI  - Tumor suppressor gene Rb is required for self-renewal of spermatogonial stem
      cells in mice.
AB  - The retinoblastoma tumor suppressor gene Rb is essential for maintaining the
      quiescence and for regulating the differentiation of somatic stem cells.
      Inactivation of Rb in somatic stem cells typically leads to their overexpansion,
      often followed by increased apoptosis, defective terminal differentiation, and
      tumor formation. However, Rb's roles in germ-line stem cells have not been
      explored. We conditionally disrupted the Rb gene in mouse germ cells in vivo and
      discovered unanticipated consequences for GFRa1-protein-expressing A(single)
      (GFRa1(+) A(s)) spermatogonia, the major source of male germ-line stem cells. Rb
      deficient GFRa1(+) A(s) spermatogonia were present at normal density in testes 5
      d after birth, but they lacked the capacity for self-renewal, resulting in germ
      cell depletion by 2 mo of age. Rb deficiency did not affect the proliferative
      activity of GFRa1(+) A(s) spermatogonia, but their progeny were exclusively
      transit-amplifying progenitor spermatogonia and did not include GFRa1(+) A(s)
      spermatogonia. In addition, Rb deficiency caused prolonged proliferation of
      progenitor spermatogonia, transiently enlarging this population. Despite these
      defects, Rb deficiency did not block terminal differentiation into functional
      sperm; offspring were readily obtained from young males whose germ cell pool was
      not yet depleted. We conclude that Rb is required for self-renewal of germ-line
      stem cells, but contrary to its critical roles in somatic stem cells, it is
      dispensable for their proliferative activity and terminal differentiation. Thus,
      this study identifies an unexpected function for Rb in maintaining the stem cell
      pool in the male germ line.

PMID- 23858446
TI  - Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B
      knockout mice.
AB  - The monoamine oxidase isoenzymes (MAOs) A and B play important roles in the
      homeostasis of monoaminergic neurotransmitters. The combined deficiency of MAO A
      and B results in significantly elevated levels of serotonin (5
      hydroxytryptamine), norepinephrine, dopamine, and beta-phenylethylamine; in
      humans and mice, these neurochemical changes are accompanied by
      neurodevelopmental perturbations as well as autistic-like responses. Ample
      evidence indicates that normal levels of monoamines in the hippocampus, amygdala,
      frontal cortex, and cerebellum are required for the integrity of learning and
      memory. Thus, in the present study, the cognitive status of MAO A/B knockout (KO)
      mice was examined with a wide array of behavioral tests. In comparison with male
      wild-type littermates, MAO A/B KO mice exhibited abnormally high and
      overgeneralized fear conditioning and enhanced eye-blink conditioning. These
      alterations were accompanied by significant increases in hippocampal long-term
      potentiation and alterations in the relative expression of NMDA glutamate
      receptor subunits. Our data suggest that chronic elevations of monoamines,
      because of the absence of MAO A and MAO B, cause functional alterations that are
      accompanied with changes in the cellular mechanisms underlying learning and
      memory. The characteristics exhibited by MAO A/B KO mice highlight the potential
      of these animals as a useful tool to provide further insight into the molecular
      bases of disorders associated with abnormal monoaminergic profiles. 

PMID- 23858448
TI  - Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex
      with the Atg11 scaffold during autophagy initiation.
AB  - Macroautophagy (hereafter autophagy) functions in the nonselective clearance of
      cytoplasm. This process participates in many aspects of cell physiology, and is
      conserved in all eukaryotes. Autophagy begins with the organization of the
      phagophore assembly site (PAS), where most of the AuTophaGy-related (Atg)
      proteins are at least transiently localized. Autophagy occurs at a basal level
      and can be induced by various types of stress; the process must be tightly
      regulated because insufficient or excessive autophagy can be deleterious. A
      complex composed of Atg17-Atg31-Atg29 is vital for PAS organization and autophagy
      induction, implying a significant role in autophagy regulation. In this study, we
      demonstrate that Atg29 is a phosphorylated protein and that this modification is
      critical to its function; alanine substitution at the phosphorylation sites
      blocks its interaction with the scaffold protein Atg11 and its ability to
      facilitate assembly of the PAS. Atg29 has the characteristics of an intrinsically
      disordered protein, suggesting that it undergoes dynamic conformational changes
      on interaction with a binding partner(s). Finally, single-particle electron
      microscopy analysis of the Atg17-Atg31-Atg29 complex reveals an elongated
      structure with Atg29 located at the opposing ends. 

PMID- 23858449
TI  - Control of a four-color sensing photoreceptor by a two-color sensing
      photoreceptor reveals complex light regulation in cyanobacteria.
AB  - Photoreceptors are biologically important for sensing changes in the color and
      intensity of ambient light and, for photosynthetic organisms, processing this
      light information to optimize food production through photosynthesis.
      Cyanobacteria are an evolutionarily and ecologically important prokaryotic group
      of oxygenic photosynthesizers that contain cyanobacteriochrome (CBCR)
      photoreceptors, whose family members sense nearly the entire visible spectrum of
      light colors. Some cyanobacteria contain 12 to 15 different CBCRs, and many
      family members contain multiple light-sensing domains. However, the complex
      interactions that must be occurring within and between these photoreceptors
      remain unexplored. Here we describe the regulation and photobiology of a unique
      CBCR called IflA (influenced by far-red light), demonstrating that a second CBCR
      called RcaE strongly regulates IflA abundance and that IflA uses two distinct
      photosensory domains to respond to four different light colors: blue, green, red,
      and far-red. The absorption of red or far-red light by one domain affects the
      conformation of the other domain, and the rate of relaxation of one of these
      domains is influenced by the conformation of the other. Deletion of iflA results
      in delayed growth at low cell density, suggesting that IflA accelerates growth
      under this condition, apparently by sensing the ratio of red to far-red light in
      the environment. The types of complex photobiological interactions described
      here, both between unrelated CBCR family members and within photosensory domains
      of a single CBCR, may be advantageous for species using these photoreceptors in
      aquatic environments, where light color ratios are influenced by many biotic and
      abiotic factors. 

PMID- 23858450
TI  - Two-codon T-box riboswitch binding two tRNAs.
AB  - T-box riboswitches control transcription of downstream genes through the tRNA
      binding formation of terminator or antiterminator structures. Previously reported
      T-boxes were described as single-specificity riboswitches that can bind specific
      tRNA anticodons through codon-anticodon interactions with the nucleotide triplet
      of their specifier loop (SL). However, the possibility that T-boxes might exhibit
      specificity beyond a single tRNA had been overlooked. In Clostridium
      acetobutylicum, the T-box that regulates the operon for the essential tRNA
      dependent transamidation pathway harbors a SL with two potential overlapping
      codon positions for tRNA(Asn) and tRNA(Glu). To test its specificity, we
      performed extensive mutagenic, biochemical, and chemical probing analyses.
      Surprisingly, both tRNAs can efficiently bind the SL in vitro and in vivo. The
      dual specificity of the T-box is allowed by a single base shift on the SL from
      one overlapping codon to the next. This feature allows the riboswitch to sense
      two tRNAs and balance the biosynthesis of two amino acids. Detailed genomic
      comparisons support our observations and suggest that "flexible" T-box
      riboswitches are widespread among bacteria, and, moreover, their specificity is
      dictated by the metabolic interconnection of the pathways under control. Taken
      together, our results support the notion of a genome-dependent codon ambiguity of
      the SLs. Furthermore, the existence of two overlapping codons imposes a unique
      example of tRNA-dependent regulation at the transcriptional level. 

PMID- 23858451
TI  - The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA
      precursor pools in mammalian cells.
AB  - Sterile alpha motif and HD-domain containing protein 1 (SAMHD1) is a
      triphosphohydrolase converting deoxynucleoside triphosphates (dNTPs) to
      deoxynucleosides. The enzyme was recently identified as a component of the human
      innate immune system that restricts HIV-1 infection by removing dNTPs required
      for viral DNA synthesis. SAMHD1 has deep evolutionary roots and is ubiquitous in
      human organs. Here we identify a general function of SAMHD1 in the regulation of
      dNTP pools in cultured human cells. The protein was nuclear and variably
      expressed during the cell cycle, maximally during quiescence and minimally during
      S-phase. Treatment of lung or skin fibroblasts with specific siRNAs resulted in
      the disappearence of SAMHD1 accompanied by loss of the cell-cycle regulation of
      dNTP pool sizes and dNTP imbalance. Cells accumulated in G1 phase with oversized
      pools and stopped growing. Following removal of the siRNA, the pools were
      normalized and cell growth restarted, but only after SAMHD1 had reappeared. In
      quiescent cultures SAMHD1 down-regulation leads to a marked expansion of dNTP
      pools. In all cases the largest effect was on dGTP, the preferred substrate of
      SAMHD1. Ribonucleotide reductase, responsible for the de novo synthesis of dNTPs,
      is a cytosolic enzyme maximally induced in S-phase cells. Thus, in mammalian
      cells the cell cycle regulation of the two main enzymes controlling dNTP pool
      sizes is adjusted to the requirements of DNA replication. Synthesis by the
      reductase peaks during S-phase, and catabolism by SAMHD1 is maximal during G1
      phase when large dNTP pools would prevent cells from preparing for a new round of
      DNA replication. 

PMID- 23858452
TI  - Characterization of the nitric oxide reductase from Thermus thermophilus.
AB  - Nitrous oxide (N2O) is a powerful greenhouse gas implicated in climate change.
      The dominant source of atmospheric N2O is incomplete biological dentrification,
      and the enzymes responsible for the release of N2O are NO reductases. It was
      recently reported that ambient emissions of N2O from the Great Boiling Spring in
      the United States Great Basin are high, and attributed to incomplete
      denitrification by Thermus thermophilus and related bacterial species [Hedlund
      BP, et al. (2011) Geobiology 9(6)471-480]. In the present work, we have isolated
      and characterized the NO reductase (NOR) from T. thermophilus. The enzyme is a
      member of the cNOR family of enzymes and belongs to a phylogenetic clade that is
      distinct from previously examined cNORs. Like other characterized cNORs, the T.
      thermophilus cNOR consists of two subunits, NorB and NorC, and contains a one
      heme c, one Ca(2+), a low-spin heme b, and an active site consisting of a high
      spin heme b and FeB. The roles of conserved residues within the cNOR family were
      investigated by site-directed mutagenesis. The most important and unexpected
      result is that the glutamic acid ligand to FeB is not essential for function. The
      E211A mutant retains 68% of wild-type activity. Mutagenesis data and the pattern
      of conserved residues suggest that there is probably not a single pathway for
      proton delivery from the periplasm to the active site that is shared by all
      cNORs, and that there may be multiple pathways within the T. thermophilus cNOR. 

PMID- 23858453
TI  - Cell-cell contacts confine public goods diffusion inside Pseudomonas aeruginosa
      clonal microcolonies.
AB  - The maintenance of cooperation in populations where public goods are equally
      accessible to all but inflict a fitness cost on individual producers is a long
      standing puzzle of evolutionary biology. An example of such a scenario is the
      secretion of siderophores by bacteria into their environment to fetch soluble
      iron. In a planktonic culture, these molecules diffuse rapidly, such that the
      same concentration is experienced by all bacteria. However, on solid substrates,
      bacteria form dense and packed colonies that may alter the diffusion dynamics
      through cell-cell contact interactions. In Pseudomonas aeruginosa microcolonies
      growing on solid substrate, we found that the concentration of pyoverdine, a
      secreted iron chelator, is heterogeneous, with a maximum at the center of the
      colony. We quantitatively explain the formation of this gradient by local
      exchange between contacting cells rather than by global diffusion of pyoverdine.
      In addition, we show that this local trafficking modulates the growth rate of
      individual cells. Taken together, these data provide a physical basis that
      explains the stability of public goods production in packed colonies. 

PMID- 23858454
TI  - Acoustophoretic contactless transport and handling of matter in air.
AB  - Levitation and controlled motion of matter in air have a wealth of potential
      applications ranging from materials processing to biochemistry and
      pharmaceuticals. We present a unique acoustophoretic concept for the contactless
      transport and handling of matter in air. Spatiotemporal modulation of the
      levitation acoustic field allows continuous planar transport and processing of
      multiple objects, from near-spherical (volume of 0.1-10 MUL) to wire-like,
      without being limited by the acoustic wavelength. The independence of the
      handling principle from special material properties (magnetic, optical, or
      electrical) is illustrated with a wide palette of application experiments, such
      as contactless droplet coalescence and mixing, solid-liquid encapsulation,
      absorption, dissolution, and DNA transfection. More than a century after the
      pioneering work of Lord Rayleigh on acoustic radiation pressure, a path-breaking
      concept is proposed to harvest the significant benefits of acoustic levitation in
      air. 

PMID- 23858456
TI  - Stone tools and foraging in northern Madagascar challenge Holocene extinction
      models.
AB  - Past research on Madagascar indicates that village communities were established
      about AD 500 by people of both Indonesian and East African heritage. Evidence of
      earlier visits is scattered and contentious. Recent archaeological excavations in
      northern Madagascar provide evidence of occupational sites with microlithic stone
      technologies related to foraging for forest and coastal resources. A forager
      occupation of one site dates to earlier than 2000 B.C., doubling the length of
      Madagascar's known occupational history, and thus the time during which people
      exploited Madagascar's environments. We detail stratigraphy, chronology, and
      artifacts from two rock shelters. Ambohiposa near Iharana (Vohemar) on the
      northeast coast, yielded a stratified assemblage with small flakes, microblades,
      and retouched crescentic and trapezoidal tools, probably projectile elements,
      made on cherts and obsidian, some brought more that 200 km. (14)C dates are
      contemporary with the earliest villages. No food remains are preserved. Lakaton'i
      Anja near Antsiranana in the north yielded several stratified assemblages. The
      latest assemblage is well dated to A.D. 1050-1350, by (14)C and optically
      stimulated luminescence dating and pottery imported from the Near East and China.
      Below is a series of stratified assemblages similar to Ambohiposa. (14)C and
      optically stimulated luminescence dates indicate occupation from at least 2000
      B.C. Faunal remains indicate a foraging pattern. Our evidence shows that foragers
      with a microlithic technology were active in Madagascar long before the arrival
      of farmers and herders and before many Late Holocene faunal extinctions. The
      differing effects of historically distinct economies must be identified and
      understood to reconstruct Holocene histories of human environmental impact. 

PMID- 23858455
TI  - Visualizing the substrate-, superoxo-, alkylperoxo-, and product-bound states at
      the nonheme Fe(II) site of homogentisate dioxygenase.
AB  - Homogentisate 1,2-dioxygenase (HGDO) uses a mononuclear nonheme Fe(2+) to
      catalyze the oxidative ring cleavage in the degradation of Tyr and Phe by
      producing maleylacetoacetate from homogentisate (2,5-dihydroxyphenylacetate).
      Here, we report three crystal structures of HGDO, revealing five different steps
      in its reaction cycle at 1.7-1.98 A resolution. The resting state structure
      displays an octahedral coordination for Fe(2+) with two histidine residues
      (His331 and His367), a bidentate carboxylate ligand (Glu337), and two water
      molecules. Homogentisate binds as a monodentate ligand to Fe(2+), and its
      interaction with Tyr346 invokes the folding of a loop over the active site,
      effectively shielding it from solvent. Binding of homogentisate is driven by
      enthalpy and is entropically disfavored as shown by anoxic isothermal titration
      calorimetry. Three different reaction cycle intermediates have been trapped in
      different HGDO subunits of a single crystal showing the influence of crystal
      packing interactions on the course of enzymatic reactions. The observed
      superoxo:semiquinone-, alkylperoxo-, and product-bound intermediates have been
      resolved in a crystal grown anoxically with homogentisate, which was subsequently
      incubated with dioxygen. We demonstrate that, despite different folds, active
      site architectures, and Fe(2+) coordination, extradiol dioxygenases can proceed
      through the same principal reaction intermediates to catalyze the O2-dependent
      cleavage of aromatic rings. Thus, convergent evolution of nonhomologous enzymes
      using the 2-His-1-carboxylate facial triad motif developed different solutions to
      stabilize closely related intermediates in unlike environments. 

PMID- 23858457
TI  - Homologous recombination rescues ssDNA gaps generated by nucleotide excision
      repair and reduced translesion DNA synthesis in yeast G2 cells.
AB  - Repair of DNA bulky lesions often involves multiple repair pathways such as
      nucleotide-excision repair, translesion DNA synthesis (TLS), and homologous
      recombination (HR). Although there is considerable information about individual
      pathways, little is known about the complex interactions or extent to which
      damage in single strands, such as the damage generated by UV, can result in
      double-strand breaks (DSBs) and/or generate HR. We investigated the consequences
      of UV-induced lesions in nonreplicating G2 cells of budding yeast. In contrast to
      WT cells, there was a dramatic increase in ssDNA gaps for cells deficient in the
      TLS polymerases eta (Rad30) and zeta (Rev3). Surprisingly, repair in TLS
      deficient G2 cells required HR repair genes RAD51 and RAD52, directly revealing a
      redundancy of TLS and HR functions in repair of ssDNAs. Using a physical assay
      that detects recombination between circular sister chromatids within a few hours
      after UV, we show an approximate three-fold increase in recombinants in the TLS
      mutants over that in WT cells. The recombination, which required RAD51 and RAD52,
      does not appear to be caused by DSBs, because a dose of ionizing radiation
      producing 20 times more DSBs was much less efficient than UV in producing
      recombinants. Thus, in addition to revealing TLS and HR functional redundancy, we
      establish that UV-induced recombination in TLS mutants is not attributable to
      DSBs. These findings suggest that ssDNA that might originate during the repair of
      closely opposed lesions or of ssDNA-containing lesions or from uncoupled
      replication may drive recombination directly in various species, including
      humans. 

PMID- 23858458
TI  - Crop manuring and intensive land management by Europe's first farmers.
AB  - The spread of farming from western Asia to Europe had profound long-term social
      and ecological impacts, but identification of the specific nature of Neolithic
      land management practices and the dietary contribution of early crops has been
      problematic. Here, we present previously undescribed stable isotope
      determinations of charred cereals and pulses from 13 Neolithic sites across
      Europe (dating ca. 5900-2400 cal B.C.), which show that early farmers used
      livestock manure and water management to enhance crop yields. Intensive manuring
      inextricably linked plant cultivation and animal herding and contributed to the
      remarkable resilience of these combined practices across diverse climatic zones.
      Critically, our findings suggest that commonly applied paleodietary
      interpretations of human and herbivore delta(15)N values have systematically
      underestimated the contribution of crop-derived protein to early farmer diets. 

PMID- 23858459
TI  - Export of submicron particulate organic matter to mesopelagic depth in an
      oligotrophic gyre.
AB  - Sixty percent of the world ocean by area is contained in oligotrophic gyres
      [Longhurst A (1995) Prog Oceanog 36:77-16], the biomass of which is dominated by
      picophytoplankton, including cyanobacteria and picoeukaryotic algae, as well as
      picoheterotrophs. Despite their recognized importance in carbon cycling in the
      surface ocean, the role of small cells and their detrital remains in the transfer
      of particulate organic matter (POM) to the deep ocean remains disputed. Because
      oligotrophic marine conditions are projected to expand under current climate
      trends, a better understanding of the role of small particles in the global
      carbon cycle is a timely goal. Here we use the lipid profiles, radiocarbon, and
      stable carbon isotopic signatures of lipids from the North Pacific Subtropical
      Gyre to show that in the surface ocean, lipids from submicron POM (here called
      extra-small POM) are distinct from larger classes of suspended POM. Remarkably,
      this distinct extra-small POM signature dominates the total lipids collected at
      mesopelagic depth, suggesting that the lipid component of mesopelagic POM
      primarily contains the exported remains of small particles. Transfer of submicron
      material to mesopelagic depths in this location is consistent with model results
      that claim the biological origin of exported carbon should be proportional to the
      distribution of cell types in the surface community, irrespective of cell size
      [Richardson TL, Jackson GA (2007) Science 315:838-840]. Our data suggest that the
      submicron component of exported POM is an important contributor to the global
      biological pump, especially in oligotrophic waters. 

PMID- 23858460
TI  - Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive
      immune system.
AB  - It has long been recognized that the T-cell compartment has more CD4 helper than
      CD8 cytotoxic T cells, and this is most evident looking at T-cell development in
      the thymus. However, it remains unknown how thymocyte development so favors CD4
      lineage development. To identify the basis of this asymmetry, we analyzed
      development of synchronized cohorts of thymocytes in vivo and estimated rates of
      thymocyte death and differentiation throughout development, inferring lineage
      specific efficiencies of selection. Our analysis suggested that roughly equal
      numbers of cells of each lineage enter selection and found that, overall, a
      remarkable ~75% of cells that start selection fail to complete the process.
      Importantly it revealed that class I-restricted thymocytes are specifically
      susceptible to apoptosis at the earliest stage of selection. The importance of
      differential apoptosis was confirmed by placing thymocytes under apoptotic
      stress, resulting in preferential death of class I-restricted thymocytes. Thus,
      asymmetric death during selection is the key determinant of the CD4:CD8 ratio in
      which T cells are generated by thymopoiesis. 

PMID- 23858461
TI  - Inhibiting the HSP90 chaperone slows cyst growth in a mouse model of autosomal
      dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a progressive genetic
      syndrome with an incidence of 1:500 in the population, arising from inherited
      mutations in the genes for polycystic kidney disease 1 (PKD1) or polycystic
      kidney disease 2 (PKD2). Typical onset is in middle age, with gradual replacement
      of renal tissue with thousands of fluid-filled cysts, resulting in end-stage
      renal disease requiring dialysis or kidney transplantation. There currently are
      no approved therapies to slow or cure ADPKD. Mutations in the PKD1 and PKD2 genes
      abnormally activate multiple signaling proteins and pathways regulating cell
      proliferation, many of which we observe, through network construction, to be
      regulated by heat shock protein 90 (HSP90). Inhibiting HSP90 with a small
      molecule, STA-2842, induces the degradation of many ADPKD-relevant HSP90 client
      proteins in Pkd1(-/-) primary kidney cells and in vivo. Using a conditional Cre
      mediated mouse model to inactivate Pkd1 in vivo, we find that weekly
      administration of STA-2842 over 10 wk significantly reduces initial formation of
      renal cysts and kidney growth and slows the progression of these phenotypes in
      mice with preexisting cysts. These improved disease phenotypes are accompanied by
      improved indicators of kidney function and reduced expression and activity of
      HSP90 clients and their effectors, with the degree of inhibition correlating with
      cystic expansion in individual animals. Pharmacokinetic analysis indicates that
      HSP90 is overexpressed and HSP90 inhibitors are selectively retained in cystic
      versus normal kidney tissue, analogous to the situation observed in solid tumors.
      These results provide an initial justification for evaluating HSP90 inhibitors as
      therapeutic agents for ADPKD. 

PMID- 23858463
TI  - Metabolic modeling of species interaction in the human microbiome elucidates
      community-level assembly rules.
AB  - The human microbiome plays a key role in human health and is associated with
      numerous diseases. Metagenomic-based studies are now generating valuable
      information about the composition of the microbiome in health and in disease,
      demonstrating nonneutral assembly processes and complex co-occurrence patterns.
      However, the underlying ecological forces that structure the microbiome are still
      unclear. Specifically, compositional studies alone with no information about
      mechanisms of interaction, potential competition, or syntrophy, cannot clearly
      distinguish habitat-filtering and species assortment assembly processes. To
      address this challenge, we introduce a computational framework, integrating
      metagenomic-based compositional data with genome-scale metabolic modeling of
      species interaction. We use in silico metabolic network models to predict levels
      of competition and complementarity among 154 microbiome species and compare
      predicted interaction measures to species co-occurrence. Applying this approach
      to two large-scale datasets describing the composition of the gut microbiome, we
      find that species tend to co-occur across individuals more frequently with
      species with which they strongly compete, suggesting that microbiome assembly is
      dominated by habitat filtering. Moreover, species' partners and excluders exhibit
      distinct metabolic interaction levels. Importantly, we show that these trends
      cannot be explained by phylogeny alone and hold across multiple taxonomic levels.
      Interestingly, controlling for host health does not change the observed patterns,
      indicating that the axes along which species are filtered are not fully defined
      by macroecological host states. The approach presented here lays the foundation
      for a reverse-ecology framework for addressing key questions concerning the
      assembly of host-associated communities and for informing clinical efforts to
      manipulate the microbiome. 

PMID- 23858464
TI  - Profile of Bruce A. Beutler.

PMID- 23858465
TI  - Flexible frequency control of cortical oscillations enables computations required
      for working memory.
AB  - Cognitive effort leads to a seeming cacophony of brain oscillations. For example,
      during tasks engaging working memory (WM), specific oscillatory frequency bands
      modulate in space and time. Despite ample data correlating such modulation to
      task performance, a mechanistic explanation remains elusive. We propose that
      flexible control of neural oscillations provides a unified mechanism for the
      rapid and controlled transitions between the computational operations required by
      WM. We show in a spiking network model that modulating the input oscillation
      frequency sets the network in different operating modes: rapid memory access and
      load is enabled by the beta-gamma oscillations, maintaining a memory while
      ignoring distractors by the theta, rapid memory clearance by the alpha. The
      various frequency bands determine the dynamic gating regimes enabling the
      necessary operations for WM, whose succession explains the need for the complex
      oscillatory brain dynamics during effortful cognition. 

PMID- 23858466
TI  - Determinants of plant establishment success in a multispecies introduction
      experiment with native and alien species.
AB  - Determinants of plant establishment and invasion are a key issue in ecology and
      evolution. Although establishment success varies substantially among species, the
      importance of species traits and extrinsic factors as determinants of
      establishment in existing communities has remained difficult to prove in
      observational studies because they can be confounded and mask each other.
      Therefore, we conducted a large multispecies field experiment to disentangle the
      relative importance of extrinsic factors vs. species characteristics for the
      establishment success of plants in grasslands. We introduced 48 alien and 45
      native plant species at different seed numbers into multiple grassland sites with
      or without experimental soil disturbance and related their establishment success
      to species traits assessed in five independent multispecies greenhouse
      experiments. High propagule pressure and high seed mass were the most important
      factors increasing establishment success in the very beginning of the experiment.
      However, after 3 y, propagule pressure became less important, and species traits
      related to biotic interactions (including herbivore resistance and responses to
      shading and competition) became the most important drivers of success or failure.
      The relative importance of different traits was environment-dependent and changed
      over time. Our approach of combining a multispecies introduction experiment in
      the field with trait data from independent multispecies experiments in the
      greenhouse allowed us to detect the relative importance of species traits for
      early establishment and provided evidence that species traits--fine-tuned by
      environmental factors--determine success or failure of alien and native plants in
      temperate grasslands.

PMID- 23858467
TI  - Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to
      Munc18a in a closed conformation.
AB  - In neurons, soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE)
      proteins drive the fusion of synaptic vesicles to the plasma membrane through the
      formation of a four-helix SNARE complex. Members of the Sec1/Munc18 protein
      family regulate membrane fusion through interactions with the syntaxin family of
      SNARE proteins. The neuronal protein Munc18a interacts with a closed conformation
      of the SNARE protein syntaxin1a (Syx1a) and with an assembled SNARE complex
      containing Syx1a in an open conformation. The N-peptide of Syx1a (amino acids 1
      24) has been implicated in the transition of Munc18a-bound Syx1a to Munc18a-bound
      SNARE complex, but the underlying mechanism is not understood. Here we report the
      X-ray crystal structures of Munc18a bound to Syx1a with and without its native N
      peptide (Syx1aDeltaN), along with small-angle X-ray scattering (SAXS) data for
      Munc18a bound to Syx1a, Syx1aDeltaN, and Syx1a L165A/E166A (LE), a mutation
      thought to render Syx1a in a constitutively open conformation. We show that all
      three complexes adopt the same global structure, in which Munc18a binds a closed
      conformation of Syx1a. We also identify a possible structural connection between
      the Syx1a N-peptide and SNARE domain that might be important for the transition
      of closed-to-open Syx1a in SNARE complex assembly. Although the role of the N
      peptide in Munc18a-mediated SNARE complex assembly remains unclear, our results
      demonstrate that the N-peptide and LE mutation have no effect on the global
      conformation of the Munc18a-Syx1a complex. 

PMID- 23858462
TI  - Phylogeny and tempo of diversification in the superradiation of spiny-rayed
      fishes.
AB  - Spiny-rayed fishes, or acanthomorphs, comprise nearly one-third of all living
      vertebrates. Despite their dominant role in aquatic ecosystems, the evolutionary
      history and tempo of acanthomorph diversification is poorly understood. We
      investigate the pattern of lineage diversification in acanthomorphs by using a
      well-resolved time-calibrated phylogeny inferred from a nuclear gene supermatrix
      that includes 520 acanthomorph species and 37 fossil age constraints. This
      phylogeny provides resolution for what has been classically referred to as the
      "bush at the top" of the teleost tree, and indicates acanthomorphs originated in
      the Early Cretaceous. Paleontological evidence suggests acanthomorphs exhibit a
      pulse of morphological diversification following the end Cretaceous mass
      extinction; however, the role of this event on the accumulation of living
      acanthomorph diversity remains unclear. Lineage diversification rates through
      time exhibit no shifts associated with the end Cretaceous mass extinction, but
      there is a global decrease in lineage diversification rates 50 Ma that occurs
      during a period when morphological disparity among fossil acanthomorphs increases
      sharply. Analysis of clade-specific shifts in diversification rates reveal that
      the hyperdiversity of living acanthomorphs is highlighted by several rapidly
      radiating lineages including tunas, gobies, blennies, snailfishes, and Afro
      American cichlids. These lineages with high diversification rates are not
      associated with a single habitat type, such as coral reefs, indicating there is
      no single explanation for the success of acanthomorphs, as exceptional bouts of
      diversification have occurred across a wide array of marine and freshwater
      habitats. 

PMID- 23858468
TI  - Structure and function of CarD, an essential mycobacterial transcription factor.
AB  - CarD, an essential transcription regulator in Mycobacterium tuberculosis,
      directly interacts with the RNA polymerase (RNAP). We used a combination of in
      vivo and in vitro approaches to establish that CarD is a global regulator that
      stimulates the formation of RNAP-holoenzyme open promoter (RPo) complexes. We
      determined the X-ray crystal structure of Thermus thermophilus CarD, allowing us
      to generate a structural model of the CarD/RPo complex. On the basis of our
      structural and functional analyses, we propose that CarD functions by forming
      protein/protein and protein/DNA interactions that bridge the RNAP to the promoter
      DNA. CarD appears poised to interact with a DNA structure uniquely presented by
      the RPo: the splayed minor groove at the double-stranded/single-stranded DNA
      junction at the upstream edge of the transcription bubble. Thus, CarD uses an
      unusual mechanism for regulating transcription, sensing the DNA conformation
      where transcription bubble formation initiates. 

PMID- 23858469
TI  - Oxygen-sensitive mitochondrial accumulation of cystathionine beta-synthase
      mediated by Lon protease.
AB  - Oxygen-sensitive accumulation and degradation, two opposite but intrinsically
      linked events, of heme proteins in mitochondria affect mitochondrial functions,
      including bioenergetics and oxygen-sensing processes. Cystathionine beta-synthase
      (CBS) contains a prosthetic heme group and catalyzes the production of hydrogen
      sulfide in mammalian cells. Here we show that CBS proteins were present in liver
      mitochondria at a low level under normoxia conditions. Ischemia/hypoxia increased
      the accumulation of CBS proteins in mitochondria. The normalization of oxygen
      partial pressure accelerated the degradation of CBS proteins. Lon protease, a
      major degradation enzyme in mitochondrial matrix, recognized and degraded
      mitochondrial CBS by specifically targeting at the oxygenated heme group of CBS
      proteins. The accumulation of CBS in mitochondria increased hydrogen sulfide
      production, which prevented Ca(2+)-mediated cytochrome c release from
      mitochondria and decreased reactive oxygen species generation. Mitochondrial
      accumulation of heme oxygenase-1, another heme protein, was also regulated by
      oxygen level and Lon protease in the same mechanism as for CBS. Our findings
      provide a fundamental and general mechanism for oxygen-sensitive regulation of
      mitochondrial functions by linking oxygenation level to the
      accumulation/degradation of mitochondrial heme proteins. 

PMID- 23858470
TI  - Leptin promotes K(ATP) channel trafficking by AMPK signaling in pancreatic beta
      cells.
AB  - Leptin is a pivotal regulator of energy and glucose homeostasis, and defects in
      leptin signaling result in obesity and diabetes. The ATP-sensitive potassium
      (K(ATP)) channels couple glucose metabolism to insulin secretion in pancreatic
      beta-cells. In this study, we provide evidence that leptin modulates pancreatic
      beta-cell functions by promoting K(ATP) channel translocation to the plasma
      membrane via AMP-activated protein kinase (AMPK) signaling. K(ATP) channels were
      localized mostly to intracellular compartments of pancreatic beta-cells in the
      fed state and translocated to the plasma membrane in the fasted state. This
      process was defective in leptin-deficient ob/ob mice, but restored by leptin
      treatment. We discovered that the molecular mechanism of leptin-induced AMPK
      activation involves canonical transient receptor potential 4 and
      calcium/calmodulin-dependent protein kinase kinase beta. AMPK activation was
      dependent on both leptin and glucose concentrations, so at optimal concentrations
      of leptin, AMPK was activated sufficiently to induce K(ATP) channel trafficking
      and hyperpolarization of pancreatic beta-cells in a physiological range of
      fasting glucose levels. There was a close correlation between phospho-AMPK levels
      and beta-cell membrane potentials, suggesting that AMPK-dependent K(ATP) channel
      trafficking is a key mechanism for regulating beta-cell membrane potentials. Our
      results present a signaling pathway whereby leptin regulates glucose homeostasis
      by modulating beta-cell excitability.

PMID- 23858471
TI  - Clonal precursor of bone, cartilage, and hematopoietic niche stromal cells.
AB  - Organs are composites of tissue types with diverse developmental origins, and
      they rely on distinct stem and progenitor cells to meet physiological demands for
      cellular production and homeostasis. How diverse stem cell activity is
      coordinated within organs is not well understood. Here we describe a lineage
      restricted, self-renewing common skeletal progenitor (bone, cartilage, stromal
      progenitor; BCSP) isolated from limb bones and bone marrow tissue of fetal,
      neonatal, and adult mice. The BCSP clonally produces chondrocytes (cartilage
      forming) and osteogenic (bone-forming) cells and at least three subsets of
      stromal cells that exhibit differential expression of cell surface markers,
      including CD105 (or endoglin), Thy1 [or CD90 (cluster of differentiation 90)],
      and 6C3 [ENPEP glutamyl aminopeptidase (aminopeptidase A)]. These three stromal
      subsets exhibit differential capacities to support hematopoietic (blood-forming)
      stem and progenitor cells. Although the 6C3-expressing subset demonstrates
      functional stem cell niche activity by maintaining primitive hematopoietic stem
      cell (HSC) renewal in vitro, the other stromal populations promote HSC
      differentiation to more committed lines of hematopoiesis, such as the B-cell
      lineage. Gene expression analysis and microscopic studies further reveal a
      microenvironment in which CD105-, Thy1-, and 6C3-expressing marrow stroma
      collaborate to provide cytokine signaling to HSCs and more committed
      hematopoietic progenitors. As a result, within the context of bone as a blood
      forming organ, the BCSP plays a critical role in supporting hematopoiesis through
      its generation of diverse osteogenic and hematopoietic-promoting stroma,
      including HSC supportive 6C3(+) niche cells. 

PMID- 23858472
TI  - Refining the pathovar paradigm via phylogenomics of the attaching and effacing
      Escherichia coli.
AB  - The attaching and effacing Escherichia coli (AEEC) are characterized by the
      presence of a type III secretion system encoded by the locus of enterocyte
      effacement (LEE). Enterohemorrhagic E. coli (EHEC) are often identified as
      isolates that are LEE+ and carry the Shiga toxin (stx)-encoding phage, which are
      labeled Shiga toxin-producing E. coli; whereas enteropathogenic E. coli (EPEC)
      are LEE+ and often carry the EPEC adherence factor plasmid-encoded bundle-forming
      pilus (bfp) genes. All other LEE+/bfp-/stx- isolates have been historically
      designated atypical EPEC. These groups have been defined based on the presence or
      absence of a limited number of virulence factors, many of which are encoded on
      mobile elements. This study describes the comparative analysis of the genomes of
      114 LEE+ E. coli isolates. Based on a whole-genome phylogeny and analysis of type
      III secretion system effectors, the AEEC are divided into five distinct genomic
      lineages. The LEE+/stx+/bfp- genomes were primarily divided into two genomic
      lineages, the O157/O55 EHEC1 and non-O157 EHEC2. The LEE+/bfp+/stx- AEEC isolates
      sequenced in this study separated into the EPEC1, EPEC2, and EPEC4 genomic
      lineages. A multiplex PCR assay for identification of each of these AEEC genomic
      lineages was developed. Of the 114 AEEC genomes analyzed, 31 LEE+ isolates were
      not in any of the known AEEC lineages and thus represent unclassified AEEC that
      in most cases are more similar to other E. coli pathovars than to text
      modification AEEC. Our findings demonstrate evolutionary relationships among
      diverse AEEC pathogens and the utility of phylogenomics for lineage-specific
      identification of AEEC clinical isolates. 

PMID- 23858474
TI  - Crystallization of CO2 ice and the absence of amorphous CO2 ice in space.
AB  - Carbon dioxide (CO2) is one of the most relevant and abundant species in
      astrophysical and atmospheric media. In particular, CO2 ice is present in several
      solar system bodies, as well as in interstellar and circumstellar ice mantles.
      The amount of CO2 in ice mantles and the presence of pure CO2 ice are significant
      indicators of the temperature history of dust in protostars. It is therefore
      important to know if CO2 is mixed with other molecules in the ice matrix or
      segregated and whether it is present in an amorphous or crystalline form. We
      apply a multidisciplinary approach involving IR spectroscopy in the laboratory,
      theoretical modeling of solid structures, and comparison with astronomical
      observations. We generate an unprecedented highly amorphous CO2 ice and study its
      crystallization both by thermal annealing and by slow accumulation of monolayers
      from the gas phase under an ultrahigh vacuum. Structural changes are followed by
      IR spectroscopy. We also devise theoretical models to reproduce different CO2 ice
      structures. We detect a preferential in-plane orientation of some vibrational
      modes of crystalline CO2. We identify the IR features of amorphous CO2 ice, and,
      in particular, we provide a theoretical explanation for a band at 2,328 cm(-1)
      that dominates the spectrum of the amorphous phase and disappears when the
      crystallization is complete. Our results allow us to rule out the presence of
      pure and amorphous CO2 ice in space based on the observations available so far,
      supporting our current view of the evolution of CO2 ice. 

PMID- 23858473
TI  - EVI1 oncoprotein interacts with a large and complex network of proteins and
      integrates signals through protein phosphorylation.
AB  - Ecotropic viral integration site-1 (EVI1) is an oncogenic zinc finger
      transcription factor whose expression is frequently up-regulated in myeloid
      leukemia and epithelial cancers. To better understand the mechanisms underlying
      EVI1-associated disease, we sought to define the EVI1 interactome in cancer
      cells. By using stable isotope labeling by amino acids in cell culture (SILAC)
      based quantitative proteomics, we could confidently assign 78 proteins as EVI1
      interacting partners for FLAG-tagged EVI1. Subsequently, we showed that 22 of 27
      tested interacting proteins could coimmunoprecipitate with endogenous EVI1
      protein, which represented an 81.5% validation rate. Additionally, by comparing
      the stable isotope labeling by amino acids in cell culture (SILAC) data with high
      throughput yeast two hybrid results, we showed that five of these proteins
      interacted directly with EVI1. Functional classification of EVI1-interacting
      proteins revealed associations with cellular transcription machinery; modulators
      of transcription; components of WNT, TGF-beta, and RAS pathways; and proteins
      regulating DNA repair, recombination, and mitosis. We also identified EVI1
      phosphorylation sites by MS analysis and showed that Ser538 and Ser858 can be
      phosphorylated and dephosphorylated by two EVI1 interactome proteins, casein
      kinase II and protein phosphatase-1alpha. Finally, mutations that impair EVI1
      phosphorylation at these sites reduced EVI1 DNA binding through its C-terminal
      zinc finger domain and induced cancer cell proliferation. Collectively, these
      combinatorial proteomic approaches demonstrate that EVI1 interacts with large and
      complex networks of proteins, which integrate signals from various different
      signaling pathways important for oncogenesis. Comprehensive analysis of the EVI1
      interactome has thus provided an important resource for dissecting the molecular
      mechanisms of EVI1-associated disease. 

PMID- 23858475
TI  - Phosphorylated histone H2A.x in porcine embryos produced by IVF and somatic cell
      nuclear transfer.
AB  - Phosphorylated histone H2A.x (H2AX139ph) is a key factor for the repair of DNA
      double-strand breaks (DSBs) and the presence of H2AX139ph foci indicates the
      sites of DSBs. In this study, we characterized the presence of H2AX139ph during
      in vitro development of porcine embryos produced by IVF and somatic cell nuclear
      transfer (SCNT). Pronuclear stage embryos produced by IVF had, on average, 9.2
      H2AX139ph foci per pronucleus. The number of H2AX139ph foci was higher in the 2
      cell-stage embryos than in the 4-cell-stage embryos fixed at 48 h post
      fertilization. The percentage of H2AX139ph-positive nuclei was higher in SCNT
      embryos that were activated with ionomycin (ION) alone than in those activated
      with ION and strontium chloride (ION+Sr(2+)). A negative correlation was found
      between the percentage of H2AX139ph-positive cells and the total number of cells
      per embryo in day 7 blastocysts produced by IVF or SCNT. Based on the detection
      of H2AX139ph foci, the findings of this study indicate that DSBs occur in a high
      proportion of porcine embryos produced by either IVF or SCNT; fast-cleaving
      embryos have fewer DSBs than slow-cleaving embryos; the oocyte activation
      protocol can affect DNA integrity in SCNT embryos; and better-quality blastocysts
      have fewer DSBs. We propose that the presence of H2AX139ph foci can be a useful
      marker of embryo quality. 

PMID- 23858476
TI  - Boar sperm tyrosine phosphorylation patterns in the presence of oviductal
      epithelial cells: in vitro, ex vivo, and in vivo models.
AB  - Spermatozoa transport through the oviduct is a controlled process that regulates
      sperm capacitation. A crucial event involved in capacitation is protein tyrosine
      phosphorylation (TP). This study was undertaken to determine whether similarities
      exist in protein TP distribution between spermatozoa bound or unbound to
      oviductal epithelial cells (OEC) in three different conditions: i) in vitro,
      spermatozoa coincubated with OEC cultures; ii) ex vivo, spermatozoa deposited in
      porcine oviductal explants from slaughtered animals; iii) in vivo, in which sows
      were inseminated and the oviduct was recovered. The localization of
      phosphotyrosine protein was determined using indirect immunofluorescence. The
      distribution of protein TP was significantly (P<0.05) different between bound and
      unbound cell populations in all experiments. In sows inseminated close to
      ovulation, spermatozoa were found mainly in the utero-tubal junction, where
      spermatozoa exhibited higher proportion of flagellum phosphorylation. Spermatozoa
      not bound to OEC exhibited high levels of protein phosphorylation (phosphorylated
      equatorial subsegment and acrosome and/or phosphorylated flagellum) in the ex
      vivo and in vivo experiments (P<0.05). However, unbound spermatozoa coincubated
      with OEC in in vitro conditions tended to show intermediate levels of TP
      (equatorial subsegment with or without phosphorylated flagellum). In spermatozoa
      bound to OEC, protein TP was located in the equatorial subsegment or presented no
      phosphorylation (P<0.05). Although sperm capacitation conditions in vivo were not
      reproducible in vitro in our experimental conditions, sperm and OEC binding
      seemed to be a mechanism for selecting spermatozoa with a low level of TP in in
      vivo, ex vivo, and in vitro experiments. 

PMID- 23858477
TI  - Prediction of spontaneous preterm labour in at-risk pregnant women.
AB  - The ability to recognise women who are at-risk of preterm labour (PTL) is often
      difficult. Over 50% of women who are identified with factors associated with an
      increased risk of preterm birth will ultimately deliver at term. The
      cervicovaginal fluid (CVF) comprises a range of proteins secreted by gestational
      tissues, making it an ideal candidate for the screening of differentially
      expressed proteins associated with PTL. CVF samples were collected from at-risk
      asymptomatic women. Two-dimensional gel electrophoresis techniques were used to
      examine the CVF proteome of women who spontaneously delivered preterm 11-22 days
      later compared with gestation-matched women who delivered at term. Five candidate
      biomarkers were selected for further validation in a larger independent cohort of
      asymptomatic women. Thioredoxin (TXN) and interleukin 1 receptor antagonist
      (IL1RN) concentrations in the CVF were found to be significantly reduced up to 90
      days prior to spontaneous PTL compared with women who subsequently delivered at
      term. TXN was able to predict spontaneous PTL within 28 days after sampling with
      a high positive predictive value (PPV) and negative predictive value (NPV) of
      75.0% and 96.4% respectively. IL1RN also showed comparable PPV and NPV of 72.7%
      and 95.7% respectively. The discovery of these differentially expressed proteins
      may assist in the development of a new predictive bedside test in identifying
      asymptomatic women who have an increased risk of spontaneous PTL. 

PMID- 23858478
TI  - Specific expression patterns and cell distribution of ancient and modern PAG in
      bovine placenta during pregnancy.
AB  - Pregnancy-associated glycoproteins (PAGs) constitute a multigenic family of
      aspartic proteinases expressed in the trophoblast of the ruminant placenta. In
      Bos taurus, this family comprises 21 members segregated into ancient and modern
      phylogenetic groups. Ancient PAGs have been reported to be synthesized throughout
      the trophoblastic cell layer whereas modern PAGs are produced by binucleate cells
      of cotyledons. The aim of this study was to investigate modern and ancient PAGs
      during gestation in cotyledonary and intercotyledonary tissues. To obtain
      convincing and innovative results despite the high sequence identity shared
      between PAGs, we designed specific tools such as amplification primers and
      antibodies. Using real-time RT-PCR, we described the transcript expression of 16
      bovine PAGs. Overall, PAGs are characterized by an increase in their expression
      during gestation. However, we demonstrated a segregation of modern PAGs in
      cotyledons and of ancient PAGs in the intercotyledonary chorion, except for the
      ancient PAG2 expressed in cotyledons. By raising specific antibodies against the
      modern PAG1 and ancient PAG11 and PAG2, we established the expression kinetics of
      the proteins using western blotting. Immunohistochemistry showed that PAGs were
      produced by specific cellular populations: PAG1 by binucleate cells in the whole
      trophoblastic layer, PAG11 was localized in binucleate cells of the
      intercotyledonary trophoblast and the chorionic plate of the cotyledon, while
      PAG2 was produced in mononucleate cells of the internal villi of the cotyledon.
      These results revealed a highly specific regulation of PAG expression and cell
      localization as a function of their phylogenetic status, suggesting distinct
      biological functions within placental tissues. 

PMID- 23858480
TI  - The impact of latent confounders in directed network analysis in neuroscience.
AB  - In the analysis of neuroscience data, the identification of task-related causal
      relationships between various areas of the brain gives insights about the network
      of physiological pathways that are active during the task. One increasingly used
      approach to identify causal connectivity uses the concept of Granger causality
      that exploits predictability of activity in one region by past activity in other
      regions of the brain. Owing to the complexity of the data, selecting components
      for the analysis of causality as a preprocessing step has to be performed. This
      includes predetermined-and often arbitrary-exclusion of information. Therefore,
      the system is confounded by latent sources. In this paper, the effect of latent
      confounders is demonstrated, and paths of influence among three components are
      studied. While methods for analysing Granger causality are commonly based on
      linear vector autoregressive models, the effects of latent confounders are
      expected to be present also in nonlinear systems. Therefore, all analyses are
      also performed for a simulated nonlinear system and discussed with regard to
      applications in neuroscience. 

PMID- 23858481
TI  - Causal inference with multiple time series: principles and problems.
AB  - I review the use of the concept of Granger causality for causal inference from
      time-series data. First, I give a theoretical justification by relating the
      concept to other theoretical causality measures. Second, I outline possible
      problems with spurious causality and approaches to tackle these problems.
      Finally, I sketch an identification algorithm that learns causal time-series
      structures in the presence of latent variables. The description of the algorithm
      is non-technical and thus accessible to applied scientists who are interested in
      adopting the method. 

PMID- 23858479
TI  - Multivariate Granger causality: an estimation framework based on factorization of
      the spectral density matrix.
AB  - Granger causality is increasingly being applied to multi-electrode
      neurophysiological and functional imaging data to characterize directional
      interactions between neurons and brain regions. For a multivariate dataset, one
      might be interested in different subsets of the recorded neurons or brain
      regions. According to the current estimation framework, for each subset, one
      conducts a separate autoregressive model fitting process, introducing the
      potential for unwanted variability and uncertainty. In this paper, we propose a
      multivariate framework for estimating Granger causality. It is based on spectral
      density matrix factorization and offers the advantage that the estimation of such
      a matrix needs to be done only once for the entire multivariate dataset. For any
      subset of recorded data, Granger causality can be calculated through factorizing
      the appropriate submatrix of the overall spectral density matrix. 

PMID- 23858482
TI  - Application of directed transfer function and network formalism for the
      assessment of functional connectivity in working memory task.
AB  - The dynamic pattern of functional connectivity during a working memory task was
      investigated by means of the short-time directed transfer function. A clear-cut
      picture of transmissions was observed with the main centres of propagation
      located in the frontal and parietal regions, in agreement with imaging studies
      and neurophysiological hypotheses concerning the mechanisms of working memory.
      The study of the time evolution revealed that most of the time short-range
      interactions prevailed, whereas the communication between the main centres of
      activity occurred more sparsely and changed dynamically in time. The patterns of
      connectivity were quantified by means of a network formalism based on assortative
      mixing--an approach novel in the field of brain networks study. By means of
      application of the above method, we have demonstrated the existence of a modular
      structure of brain networks. The strength of interaction inside the modules was
      higher than between modules. The obtained results are compatible with theories
      concerning metabolic energy saving and efficient wiring in the brain, which
      showed that preferred organization includes modular structure with dense
      connectivity inside the modules and more sparse connections between the modules.
      The presented detailed temporal and spatial patterns of propagation are in line
      with the neurophysiological hypotheses concerning the role of gamma and theta
      activity in information processing during a working memory task.

PMID- 23858483
TI  - Time-variant partial directed coherence for analysing connectivity: a
      methodological study.
AB  - For the past decade, the detection and quantification of interactions within and
      between physiological networks has become a priority-in-common between the fields
      of biomedicine and computer science. Prominent examples are the interaction
      analysis of brain networks and of the cardiovascular-respiratory system. The aim
      of the study is to show how and to what extent results from time-variant partial
      directed coherence analysis are influenced by some basic estimator and data
      parameters. The impacts of the Kalman filter settings, the order of the
      autoregressive (AR) model, signal-to-noise ratios, filter procedures and volume
      conduction were investigated. These systematic investigations are based on data
      derived from simulated connectivity networks and were performed using a Kalman
      filter approach for the estimation of the time-variant multivariate AR model.
      Additionally, the influence of electrooculogram artefact rejection on the
      significance and dynamics of interactions in 29 channel electroencephalography
      recordings, derived from a photic driving experiment, is demonstrated. For
      artefact rejection, independent component analysis was used. The study provides
      rules to correctly apply particular methods that will aid users to achieve more
      reliable interpretations of the results. 

PMID- 23858484
TI  - A framework for assessing frequency domain causality in physiological time series
      with instantaneous effects.
AB  - We present an approach for the quantification of directional relations in
      multiple time series exhibiting significant zero-lag interactions. To overcome
      the limitations of the traditional multivariate autoregressive (MVAR) modelling
      of multiple series, we introduce an extended MVAR (eMVAR) framework allowing
      either exclusive consideration of time-lagged effects according to the classic
      notion of Granger causality, or consideration of combined instantaneous and
      lagged effects according to an extended causality definition. The spectral
      representation of the eMVAR model is exploited to derive novel frequency domain
      causality measures that generalize to the case of instantaneous effects the known
      directed coherence (DC) and partial DC measures. The new measures are illustrated
      in theoretical examples showing that they reduce to the known measures in the
      absence of instantaneous causality, and describe peculiar aspects of directional
      interaction among multiple series when instantaneous causality is non-negligible.
      Then, the issue of estimating eMVAR models from time-series data is faced,
      proposing two approaches for model identification and discussing problems related
      to the underlying model assumptions. Finally, applications of the framework on
      cardiovascular variability series and multichannel EEG recordings are presented,
      showing how it allows one to highlight patterns of frequency domain causality
      consistent with well-interpretable physiological interaction mechanisms. 

PMID- 23858486
TI  - Classification of cardiovascular time series based on different coupling
      structures using recurrence networks analysis.
AB  - We analyse cardiovascular time series with the aim of performing early prediction
      of preeclampsia (PE), a pregnancy-specific disorder causing maternal and foetal
      morbidity and mortality. The analysis is made using a novel approach, namely the
      epsilon-recurrence networks applied to a phase space constructed by means of the
      time series of the variabilities of the heart rate and the blood pressure
      (systolic and diastolic). All the possible coupling structures among these
      variables are considered for the analysis. Network measures such as average path
      length, mean coreness, global clustering coefficient and scale-local transitivity
      dimension are computed and constitute the parameters for the subsequent quadratic
      discriminant analysis. This allows us to predict PE with a sensitivity of 91.7
      per cent and a specificity of 68.1 per cent, thus validating the use of this
      method for classifying healthy and preeclamptic patients. 

PMID- 23858485
TI  - Evolution of cardiorespiratory interactions with age.
AB  - We describe an analysis of cardiac and respiratory time series recorded from 189
      subjects of both genders aged 16-90. By application of the synchrosqueezed
      wavelet transform, we extract the respiratory and cardiac frequencies and phases
      with better time resolution than is possible with the marked events procedure. By
      treating the heart and respiration as coupled oscillators, we then apply a method
      based on Bayesian inference to find the underlying coupling parameters and their
      time dependence, deriving from them measures such as synchronization, coupling
      directionality and the relative contributions of different mechanisms. We report
      a detailed analysis of the reconstructed cardiorespiratory coupling function, its
      time evolution and age dependence. We show that the direct and indirect
      respiratory modulations of the heart rate both decrease with age, and that the
      cardiorespiratory coupling becomes less stable and more time-variable. 

PMID- 23858487
TI  - Estimating coupling directions in the cardiorespiratory system using recurrence
      properties.
AB  - The asymmetry of coupling between complex systems can be studied by conditional
      probabilities of recurrence, which can be estimated by joint recurrence plots.
      This approach is applied for the first time on experimental data: time series of
      the human cardiorespiratory system in order to investigate the couplings between
      heart rate, mean arterial blood pressure and respiration. We find that the
      respiratory system couples towards the heart rate, and the heart rate towards the
      mean arterial blood pressure. However, our analysis could not detect a clear
      coupling direction between the mean arterial blood pressure and respiration. 

PMID- 23858488
TI  - Unified asymptotic theory for all partial directed coherence forms.
AB  - This paper presents a unified mathematical derivation of the asymptotic behaviour
      of the three main forms of partial directed coherence (PDC). Numerical examples
      are used to contrast PDC, gPDC (generalized PDC) and iPDC (information PDC) as to
      meaning and applicability and, more importantly, to show their essential
      statistical equivalence insofar as connectivity inference is concerned. 

PMID- 23858489
TI  - Cardiovascular control and time domain Granger causality: insights from selective
      autonomic blockade.
AB  - We studied causal relations among heart period (HP), systolic arterial pressure
      (SAP) and respiration (R) according to the definition of Granger causality in the
      time domain. Autonomic pharmacological challenges were used to alter the
      complexity of cardiovascular control. Atropine (AT), propranolol and clonidine
      (CL) were administered to block muscarinic receptors, beta-adrenergic receptors
      and centrally sympathetic outflow, respectively. We found that: (i) at baseline,
      HP and SAP interacted in a closed loop with a dominant causal direction from HP
      to SAP; (ii) pharmacological blockades did not alter the bidirectional closed
      loop interactions between HP and SAP, but AT reduced the dominance of the causal
      direction from HP to SAP; (iii) at baseline, bidirectional interactions between
      HP and R were frequently found; (iv) the closed-loop relation between HP and R
      was unmodified by the administration of drugs; (v) at baseline, unidirectional
      interactions from R to SAP were often found; and (vi) while AT induced frequently
      an uncoupling between R and SAP, CL favoured bidirectional interactions. These
      results prove that time domain measures of Granger causality can contribute to
      the description of cardiovascular control by suggesting the temporal direction of
      the interactions and by separating different causality schemes (e.g. closed loop
      versus unidirectional relations). 

PMID- 23858490
TI  - Cardiovascular and cardiorespiratory coupling analyses: a review.
AB  - Recently, methods have been developed to analyse couplings in dynamic systems. In
      the field of medical analysis of complex cardiovascular and cardiorespiratory
      systems, there is growing interest in how insights may be gained into the
      interaction between regulatory mechanisms in healthy and diseased persons. The
      couplings within and between these systems can be linear or nonlinear. However,
      the complex mechanisms involved in cardiovascular and cardiorespiratory
      regulation very likely interact with each other in a nonlinear way. Recent
      advances in nonlinear dynamics and information theory have allowed the
      multivariate study of information transfer between time series. They therefore
      might be able to provide additional diagnostic and prognostic information in
      medicine and might, in particular, be able to complement traditional linear
      coupling analysis techniques. In this review, we describe the approaches (Granger
      causality, nonlinear prediction, entropy, symbolization, phase synchronization)
      most commonly applied to detect direct and indirect couplings between time
      series, especially focusing on nonlinear approaches. We will discuss their
      capacity to quantify direct and indirect couplings and the direction (driver
      response relationship) of the considered interaction between different biological
      time series. We also give their basic theoretical background, their basic
      requirements for application, their main features and demonstrate their
      usefulness in different applications in the field of cardiovascular and
      cardiorespiratory coupling analyses. 

PMID- 23858491
TI  - Assessing causality in brain dynamics and cardiovascular control.

PMID- 23858492
TI  - A correlation study of eye lens dose and personal dose equivalent for
      interventional cardiologists.
AB  - This paper presents the dosimetry part of the European ELDO project, funded by
      the DoReMi Network of Excellence, in which a method was developed to estimate
      cumulative eye lens doses for past practices based on personal dose equivalent
      values, H(p)(10), measured above the lead apron at several positions at the
      collar, chest and waist levels. Measurement campaigns on anthropomorphic phantoms
      were carried out in typical interventional settings considering different tube
      projections and configurations, beam energies and filtration, operator positions
      and access routes and using both mono-tube and biplane X-ray systems.
      Measurements showed that eye lens dose correlates best with H(p)(10) measured on
      the left side of the phantom at the level of the collar, although this
      correlation implicates high spreads (41 %). Nonetheless, for retrospective dose
      assessment, H(p)(10) records are often the only option for eye dose estimates and
      the typically used chest left whole-body dose measurement remains useful.

PMID- 23858493
TI  - Appraisals and responses to experimental symptom analogues in clinical and
      nonclinical individuals with psychotic experiences.
AB  - OBJECTIVE: Cognitive models of psychosis suggest that anomalous experiences alone
      do not always lead to clinical psychosis, with appraisals and responses to
      experiences being central to understanding the transition to "need for care".
      METHODS: The appraisals and response styles of Clinical (C; n = 28) and
      Nonclinical (NC; n = 34) individuals with psychotic experiences were compared
      following experimental analogues of thought interference (Cards Task) and
      auditory hallucinations (Virtual Acoustic Space Paradigm). RESULTS: The groups
      were matched in terms of their psychotic experiences. As predicted, the C group
      scored higher than the NC group on maladaptive appraisals following both tasks,
      rated the experience as more personally significant, and was more likely to
      incorporate the experimental setup into their ongoing experiences. The C group
      also appraised the Cards Task as more salient, distressing, and threatening; this
      group scored higher on maladaptive-and lower on adaptive-response styles, than
      the NC group on both tasks. CONCLUSIONS: The findings are consistent with
      cognitive models of psychosis, with maladaptive appraisals and response styles
      characterizing the C group only. Clinical applications of both tasks are
      suggested to facilitate the identification and modification of maladaptive
      appraisals.

PMID- 23858494
TI  - HPV vaccination to prevent anal cancer in men who have sex with men.

PMID- 23858495
TI  - Managing STIs in primary care: pragmatic guidance for GPs from BASHH.

PMID- 23858496
TI  - Growing evidence that HPV infection is associated with an increase in HIV
      acquisition: exploring the issue of HPV vaccination.

PMID- 23858497
TI  - Assessing the sexual violence services currently provided in genitourinary
      medicine clinics.

PMID- 23858498
TI  - Are specialist-led genital dermatology clinics a valuable and necessary part of
      sexual health service provision in the UK?

PMID- 23858499
TI  - Measures of risk do not discriminate between MSM tested for HIV within the
      previous 6 months and MSM tested 6-12 months previously: data from Glasgow,
      Scotland, in 2010.

PMID- 23858500
TI  - Are we missing pharyngeal and rectal infections in women by not testing those who
      report oral and anal sex?

PMID- 23858501
TI  - How can healthcare services for female sex workers be better tailored to meet
      their health needs?

PMID- 23858502
TI  - A patient with the rare alpha-1-antitrypsin variant (Z)bristol in compound
      heterozygosity with the Z mutation.
AB  - Alpha-1-antitrypsin (AAT) is a protease inhibitor (PI), deficiency of which is
      associated with emphysema and liver disease. The most common deficiency alleles
      are the S (p.Glu288Val) and Z (p.Glu366Lys) alleles. The Z allele predisposes the
      AAT protein to polymerization with accumulation in hepatocytes leading to liver
      disease in PIZ individuals. Most AAT variants have a characteristic pattern of
      isoforms by isoelectric focusing (IEF). A novel AAT variant called PIZbristol
      (p.Thr109Met) with an unusual pattern on IEF was described in 1997. We report a
      patient with the PIZZbristol phenotype that has not been previously described. A
      43-year-old man was referred by his GP to a respiratory clinic for
      breathlessness. His AAT concentration was 0.50 g/L (reference range 1.0-2.0 g/L).
      An unusual pattern on IEF was seen and sequencing revealed the presence of the
      rare variant Zbristol in combination with the Z mutation. This is the second
      reported case of Zbristol and the first in combination with the Z mutation. The
      patient maintained plasma AAT concentrations around 0.50-0.70 g/L which suggested
      that the Zbristol protein contributed to the low plasma concentration of AAT. The
      clinical symptoms associated with PIZ are usually attributed to the plasma
      deficiency, but his only respiratory complaint was that of breathlessness. This
      suggests that the PIZZbristol phenotype may confer an effect on respiratory
      function but is not involved in liver disease. 

PMID- 23858503
TI  - Immunological detection of large oxidized lipoproteins in hypertriglyceridemic
      serum.
AB  - BACKGROUND: Triglyceride-rich, low-density lipoproteins (TG-rich LDL) have been
      reported as an oxidized lipoprotein species in patients with severe liver
      disease. Using TG-rich LDL as an immunogen, we obtained a monoclonal antibody
      (G11-6) that reacted with TG-rich LDL from patients with liver disease and with
      metal-oxidized LDL only in the early process of the oxidation reaction. This
      study determined the G11-6-reactive lipoproteins in hypertriglyceridemic serum.
      METHODS: Serum samples from healthy volunteers (n = 12) and hypertriglyceridemic
      patients (n = 9) were fractionated by gel filtration and subjected to a sandwich
      enzyme-linked immunosorbent assay (ELISA) using G11-6 and polyclonal anti
      apolipoprotein B antibodies. RESULTS: Small LDL and larger lipoproteins reacted
      with G11-6. G11-6-reactive small LDL was identified in both the healthy subjects
      and hypertriglyceridemic patients, whereas G11-6-reactive larger lipoproteins
      were found only in the hypertriglyceridemic patients. CONCLUSIONS: G11-6 is a
      useful tool for detecting increased large oxidized lipoproteins in
      hypertriglyceridemic patients.

PMID- 23858504
TI  - Normative data on axial rotation of atlanto-occipital joint on 3 Tesla MRI using
      a simple and reliable method of calculation.
AB  - BACKGROUND: Various methods have been used to image and measure the normal range
      of axial rotation of the atlanto-occipital joint (AOJ), but a simple, precise,
      and reliable method is needed for everyday practice. PURPOSE: To generate
      normative ranges for AOJ rotation in various in-vivo positions and to investigate
      the reliability of a simple imaging method for measurement using routine high
      field magnetic resonance imaging (MRI). MATERIAL AND METHODS: One hundred healthy
      volunteers were imaged on 3 T MRI with the AOJ in the center of the field of
      view. The scans were uniformly performed in seven different positions. The range
      of axial rotation was calculated by the angle between the craniofacial midline
      and the line linking the anterior and posterior tubercles of the atlas. The angle
      was defined as positive when it was angled right, and negative when it was angled
      left. The actual normative range of axial rotation was the difference between the
      angle in the supine neutral position and in the other positions. RESULTS: The
      normative axial rotation range of the AOJ in different positions was between -4.8
      degrees  and +5.0 degrees . The mean values of the actual rotation angles in the
      right supine position with maximum bending, the right supine position maximum
      rotation, and the right prostrate position maximum rotation were 0.1 degrees ,
      1.70 degrees , and 0.8 degrees , respectively. The mean values of actual rotation
      angles in the left supine position with maximum bending, the left supine position
      with maximum rotation, and the left prostrate positive with maximum rotation were
      0.1 degrees , -1.7 degrees , and -1.1 degrees , respectively. The inter-observer
      reliability tested. CONCLUSION: A simple and reliable method of measurement on
      3.0 T MRI demonstrated the normative axial rotation range of the AOJ in different
      positions to be between -4.8 degrees  and +5.0 degrees  and it was different from
      zero in neutral rotation. This method could be practically used to precisely
      diagnose AOJ rotary subluxation or dislocation.

PMID- 23858505
TI  - Ectopic pancreas in upper gastrointestinal tract: MRI findings with emphasis on
      differentiation from submucosal tumor.
AB  - BACKGROUND: Ectopic pancreas can frequently be mistaken for other submucosal
      masses. Ectopic pancreas may follow the signal intensity of mother pancreas on
      various magnetic resonance (MR) sequences, which might be helpful for
      differentiation between ectopic pancreas and other submucosal tumors in upper
      gastrointestinal (UGI) tract. PURPOSE: To evaluate the value of MR imaging (MRI)
      in differentiating ectopic pancreases from submucosal tumors in UGI tract.
      MATERIAL AND METHODS: Fifteen patients with ectopic pancreas and 26 patients with
      UGI submucosal tumors were included. All patients underwent abdominal MRI with
      diffusion-weighted imaging (DWI) and gadoxetic acid-enhanced MRI. Qualitative
      (location, contour, growth pattern, lesion border, and presence of intralesional
      cystic portion and duct-like structure) and quantitative (long diameter [LD],
      short diameter [SD], LD/SD ratio, signal intensities and apparent diffusion
      coefficients [ADC], and signal intensity - and ADC ratios of UGI submucosal
      lesions to pancreas) parameters were compared between ectopic pancreases and UGI
      submucosal tumors using Fisher's exact test, the Mann-Whitney U test, and
      receiver-operating characteristic (ROC) analysis. RESULTS: Duodenum was the most
      common location for ectopic pancreas (12/15, 79.9%), and the gastric body for UGI
      submucosal tumors (15/26, 57.7%) (P = 0.005). Round shape was an imaging feature
      more common in UGI submucosal tumors (12/26, 46.2%) than in ectopic pancreas
      (1/15, 6.7%; P = 0.021). On all of the various pulse sequences of MR images,
      ectopic pancreas showed isointensity comparable to that of pancreas more
      frequently than did sequences of UGI submucosal tumors (P < 0.01).The means (0.95
      +/- 0.09, 0.99 +/- 0.06, 1.07 +/- 0.08) of the signal intensity ratio of ectopic
      pancreas to pancreas on fat-suppressed unenhanced T1-weighted, arterial, and
      portal phase images were significantly higher than those (0.60 +/- 0.09, 0.62 +/-
      0.28, 0.86 +/- 0.27) of UGI submucosal tumors (P < 0.05). In contrast, the means
      (1.05 +/- 0.12, 0.93 +/- 0.18) of the signal intensity ratios of ectopic pancreas
      on T2-weighted images and DW images (b = 800 s/mm(2)) were significantly lower
      than those (1.82 +/- 0.39, 2.35 +/- 0.94) of UGI submucosal tumors (P < 0.001).
      On ROC analysis, if absolute value of difference between 1.0 and signal intensity
      ratio of submucosal lesions to the pancreas on T1-weighted images is <0.21, the
      sensitivity and specificity reach 100.0% for diagnosis ectopic pancreas from
      submucosal tumors. CONCLUSION: Abdominal MRI with DWI can be a valuable tool for
      differentiating ectopic pancreases from UGI submucosal tumors.

PMID- 23858506
TI  - Improving the Gleason grading accuracy of transrectal ultrasound-guided biopsy.
AB  - BACKGROUND: Transrectal ultrasound (TRUS)-guided prostate biopsy is the technique
      of choice for the assessment of clinical suspicion of prostate cancer (PC) based
      on abnormal digital rectal examination (DRE) and/or elevated or rising levels of
      prostate-specific antigen (PSA). PURPOSE: To identify factors involved in TRUS
      guided prostate biopsy, which can be modified by radiologists in order to improve
      Gleason score (GS) accuracy, and to assess the influence of clinical variables.
      MATERIAL AND METHODS: We carried out a retrospective review of the records of 185
      patients with PC treated surgically at our hospital between 2005 and 2008. Biopsy
      schemes were classified according to the number of cores (<=7, 8-9, 10-11, 12-15)
      and the needle length (11, 16, 20 mm). Clinical characteristics - age, family
      history of PC, DRE, PSA levels, and sonographic data - and prostatectomy GS (pGS)
      were collected. RESULTS: Non-random concordance between biopsy Gleason score
      (bGS) and pGS was obtained for 36% of patients (P < 0.001). Under- and over
      staging were 30% and 4%, respectively. Concordance was correlated with the core
      number (45% for <=7, 54% for 8-9, 85% for 10-11, and 80% for 12-15; P < 0.001),
      but not with the needle length. The concordance rate showed a seven-fold increase
      when 10-11 cores were obtained (95% CI, 2-18; P < 0.001) compared to those cases
      in which the core number obtained was <=7. Among clinical variables, only PSA
      correlated with concordance, showing an inverse relationship. CONCLUSION: The
      Gleason correlation values were not improved when 12 or more cores were
      collected. These values reached a plateau beyond that number of samples.
      Therefore, when determining treatment strategies, physicians must consider the
      biopsy scheme used since it has proven to be a predictor of the accuracy of the
      PC grading system.

PMID- 23858507
TI  - Can clinical and MRI findings predict the prognosis of variant and classical type
      of posterior reversible encephalopathy syndrome (PRES)?
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is characterized
      by clinical symptoms that are associated with bilateral and symmetric vasogenic
      edema in the parietal and occipital lobes. However, this is rarely present with
      predominant involvement of the brain stem and cerebellum (variant). PURPOSE: To
      evaluate which clinical or magnetic resonance imaging (MRI) findings can help to
      predict the prognosis of variant and classical type of PRES and whether or not
      there is difference between two types of PRES. MATERIAL AND METHODS: We
      retrospectively evaluated MRI and clinical findings from 49 patients with PRES.
      These patients were divided into two groups. In group I, patients had atypical
      distribution of lesions. In group II, patients had typical distribution of
      lesions. Follow-up MRI was performed on 26 patients. We assessed the MRI
      features, clinical data, and the patients' outcomes. RESULTS: The mean blood
      pressure (BP) was significantly higher in group I (195.52/121.09 mmHg and
      156.78/99.53 mmHg for groups I and II, respectively). The other factors assessed
      were not significantly different between the two groups. Lesions in 24 of 26
      patients reversed upon follow-up. Sequelae were observed in 11 patients (group I,
      7; group II, 4). However, there were no significant differences between the two
      groups. Except for those patients who died, seven of the nine patients with
      sequelae upon follow-up imaging had hemorrhage or irreversibility of lesions.
      CONCLUSION: Even though BP influences the involvement of the brain stem,
      involvement of the brain stem is not influential on the prognosis. It seems that
      the influential factor to prognosis is the reversibility of lesions and
      hemorrhage.

PMID- 23858508
TI  - Incidental thyroid lesions identified by ultrasound in patients with non
      thyroidal head and neck cancer.
AB  - BACKGROUND: Thyroid cancer is one of the common head and neck malignancies and
      may be found incidentally with other head and neck cancers. PURPOSE: To evaluate
      the prevalence and risk of malignancy in incidental thyroid lesions identified by
      ultrasound (US) in patients with head and neck cancer. MATERIAL AND METHODS: We
      retrospectively reviewed medical records of all patients with head and neck
      cancer other than of thyroid origin between January 2004 and December 2011. A
      total of 690 patients (537 men and 153 women; mean age, 58.9 +/- 12.9 years)
      underwent US of the neck for the evaluation of cervical lymph node status
      (including thyroid gland). We evaluated the prevalence of patients with
      incidental thyroid lesions identified by US and the risk of malignancy in these
      patients. RESULTS: Of the 690 patients with head and neck cancer, 234 (33.9%) had
      incidental thyroid lesions on US. Based on US findings, 61 patients underwent
      fine-needle aspiration, with 39 eventually undergoing thyroidectomy. Among these
      thyroid lesions, 24 incidental thyroid lesions of 22 patients were histologically
      proven to be malignant (23 papillary and 1 follicular carcinomas). The risk of
      malignancy was 9.4% on a patient-by-patient basis. CONCLUSION: Screening of the
      thyroid gland should be included in the preoperative US examination for cervical
      lymph node metastases in patients with non-thyroidal head and neck cancer.

PMID- 23858509
TI  - Biexponential analysis of diffusion-weighted imaging: comparison of three
      different calculation methods in transplanted kidneys.
AB  - BACKGROUND: Biexponential analysis has been used increasingly to obtain
      contributions of both diffusion and microperfusion to the signal decay in
      diffusion-weighted imaging DWI of different parts of the body. PURPOSE: To
      compare biexponential diffusion parameters of transplanted kidneys obtained with
      three different calculation methods. MATERIAL AND METHODS: DWI was acquired in 15
      renal allograft recipients (eight men, seven women; mean age, 52.4 +/- 14.3
      years) using a paracoronal EPI sequence with 16 b-values (b = 0-750 s/mm(2)) and
      six averages at 1.5T. No respiratory gating was used. Three different calculation
      methods were used for the calculation of biexponential diffusion parameters: Fp,
      ADCP, and ADCD were calculated without fixing any parameter a priori (calculation
      method 1); ADCP was fixed to 12.0 um(2)/ms, whereas Fp and ADCD were calculated
      using the biexponential model (calculation method 2); multistep approach with
      monoexponential fitting of the high b-value portion (b >= 250 s/mm(2)) for
      determination of ADCD and assessment of the low b intercept for determination of
      Fp (calculation method 3). For quantitative analysis, ROI measurements were
      performed on the according parameter maps. RESULTS: Mean ADCD values of the renal
      cortex using calculation method 1 were significantly lower than using calculation
      methods 2 and 3 (P < 0.001). There was a significant correlation between
      calculation methods 1 and 2 (r = 0.69 (P < 0.005) and calculation methods 1 and 3
      (r = 0.59; P < 0.05) as well as calculation methods 2 and 3 (r = 0.98; P <
      0.001). Mean Fp values of the renal cortex were higher with calculation method 1
      than with calculation methods 2 and 3 (P < 0.001). For Fp, only the correlation
      between calculation methods 2 and 3 was significant (r = 0.98; P < 0.001).
      CONCLUSION: Biexponential diffusion parameters differ significantly depending on
      the calculation methods used for their calculation.

PMID- 23858510
TI  - Broad overview of a clinical and commercial experience with CoolSculpting.
AB  - BACKGROUND: Cryolipolysis has been shown to be a safe and effective noninvasive
      procedure for the reduction of localized subcutaneous fat. OBJECTIVES: The
      authors examine the safety, efficacy, and procedural growth of cryolipolysis (via
      the CoolSculpting device; Zeltiq, Pleasanton, California) in a single plastic
      surgery practice. METHODS: A retrospective chart review was conducted for 528
      consecutive patients who underwent cryolipolysis treatment from January 2010 to
      December 2012. The number of patients, the number of treatment cycles, the
      average number of cycles per patient, all treatment areas, and all procedural
      complications were recorded and analyzed. Overall practice growth with the device
      was also analyzed. RESULTS: Over the study period, 1785 anatomic sites were
      treated with 2729 cycles, primarily in the lower abdomen (28%, n = 490 cycles),
      upper abdomen (11%, n = 189), left flank (19%, n = 333), right flank (19%, n =
      333), inner thigh (6%, n = 111), outer thigh (5%, n = 87), and back (6%, n = 99).
      The age distribution for men and women was similar (46.6 +/- 12.8 years for women
      and 46.5 +/- 12.3 years for men; overall range, 18-79 years). Only 3 cases of
      mild or moderate pain/neuralgia were reported and resolved in 4 or fewer days. No
      adverse events were reported. Procedure volume showed consistent growth, with
      treatment cycles increasing by 823% by 2012. CONCLUSIONS: Based on the results in
      this single plastic surgery practice, cryolipolysis is a safe and effective
      nonsurgical body contouring method associated with high patient satisfaction that
      can generate steady, significant business growth.

PMID- 23858511
TI  - Gender-based seasonality of suicide in Japan, 2005-2012.
AB  - This study aimed to explore the gender-based seasonal patterns of suicide in
      Japan between 2005 and 2012. With data from Japanese official reports, we carried
      out Prais-Winsten regression and Wilcoxon signed-rank test analysis with Stata
      12.0 and SPSS 14.0. The suicide number was significantly higher in March, April,
      May, June, July, and October for both genders. The suicide number in men was
      markedly higher than that in women in every month. The suicide number in 2010 was
      lower than that in 2009 for men, while that in 2011 was higher than that in 2010
      for women. The findings displayed that the nationwide television and publicity
      intervention campaigns might have positive effects on decreasing suicide of men
      while women suffered a post-earthquake increase. In terms of interventions, we
      should not only square up the seasonal patterns but also the gender differences
      in vulnerability. 

PMID- 23858512
TI  - Factors influencing unmet need for health care services in Korea.
AB  - This study was conducted to investigate the prevalence of unmet need based on
      both subjective assessment and adjustments for need-predicted utilization and to
      examine factors associated with them. Data from the Fourth Korea National Health
      and Nutrition Examination Survey, a population-based, cross-sectional study, were
      used in this study. Participants included 11 620 Koreans (4959 males and 6661
      females) aged 19 and older. The results for subjective unmet need suggested that
      female or younger individuals were more likely to experience unmet need, compared
      to male or older individuals. Those residing outside the capital had a higher
      likelihood of experiencing unmet need. Lower levels of education showed an
      association with higher odds of having unmet need. This study found similar
      results for the adjusted unmet need. The findings of this study suggest that
      location and education are more important factors associated with unmet need than
      income levels. 

PMID- 23858513
TI  - Effects of acculturation on lifestyle and health status among older Vietnam-born
      Australians.
AB  - Vietnamese immigrants represent a substantial culturally and linguistically
      diverse population of Australia, but little is known about the health-related
      effects of acculturation in this population. This study investigated the
      relationship between measures of acculturation and lifestyle behaviors and health
      status among 797 older Vietnam-born Australians who participated in the 45 and Up
      Study (www.45andup.org.au). The findings suggested that higher degrees of
      acculturation were associated with increased consumption of red meat, white meat,
      and seafood; higher levels of physical activities; and lower prevalence of
      overweight and obesity, type 2 diabetes, and smoking (in men). Targeted health
      messages could emphasize eating more vegetables, avoiding smoking and alcohol
      drinking, and increasing levels of physical activity. 

PMID- 23858514
TI  - Relationship between dietary patterns and cognitive function in a community
      dwelling population in Japan.
AB  - The purpose of this study was to clarify the association between dietary patterns
      and cognitive function in a community-dwelling population in Japan. A total of
      388 volunteers (60 years and older) who participated in the Iwaki Health
      Promotion Project 2011 were recruited. Diet was assessed with a validated, self
      administered brief-type diet history questionnaire. Dietary patterns were
      extracted from 52 predefined food groups by principal component analysis. The
      Mini-Mental State Examination was also used to measure global cognitive status.
      Three dietary patterns were identified as follows: "Healthy," "Noodle," and
      "Alcohol and accompaniment." Compared with the low tertile of the "Alcohol and
      accompaniment" pattern, only the middle tertile was independently related to an
      increased risk of poor cognitive function. In conclusions, present study failed
      to substantiate dose-dependent associations between dietary patterns and the risk
      of poor cognitive function. Further studies with longitudinal observations are
      warranted. 

PMID- 23858515
TI  - Socioeconomic determinants of iron-deficiency anemia among children aged 6 to 59
      months in India.
AB  - The extent of anemia and its socioeconomic determinants among the preschool
      children (6-59 months old) in India have been studied in this article. Relevant
      data are taken from the third round of the National Family Health Survey. The
      initial analysis reveals some interesting features. The most affected children
      are in the age-group of 6 to 23 months. Beyond this age a decreasing trend is
      observed up to the age of 48 to 59 months. The highest and the lowest prevalence
      of anemia have been found to be in the central and the northeast zones,
      respectively. The vulnerable groups are the children of illiterate parents and
      those belonging to the poor families in the rural areas. Categorical logistic
      regression also confirms that status of literacy and wealth of parents have
      strong negative association with the status of anemia of the children. 

PMID- 23858516
TI  - Is what Filipino children eat between meals associated with body mass index?
AB  - The study aimed to assess the association between childhood obesity and snacking.
      A total of 396 students in grades 4 to 6 enrolled in an elementary school in the
      Philippines were the participants in this study. Demographic profile;
      anthropometric measures of height, weight, body mass index; and information about
      snacking were gathered. Obese group had statistically more servings of sweetened
      drinks and low-quality snacks. Female obese subjects have statistically more
      servings at nighttime and greater total snack servings. For the whole cohort, the
      odds ratio of being overweight with high total snack servings was 2.12 (95%
      confidence interval = 1.25-3.62) whereas the odds ratio of being obese with
      calories obtained from snacking was 2.08 (95% confidence interval = 1.01-4.26).
      Nighttime snacks and bad-quality foods should be minimized. Moreover, reducing
      food portions at any snack time will protect children from being overweight. 

PMID- 23858517
TI  - Factors associated with traditional Chinese medicine utilization among urban
      community health centers in Hubei Province of China.
AB  - This study aims to examine resources and utilization of traditional Chinese
      medicine (TCM) and factors influencing TCM utilization in urban community health
      centers (CHCs) in Hubei Province of China. A cross-sectional survey including 234
      government-owned CHCs was conducted in 2009. One-way analysis of variance
      analysis and a Poisson regression model were used to examine distribution of TCM
      resources and factors influencing TCM utilization. This study found unequal
      distribution of TCM resources among districts. TCM outpatient visits were
      positively associated with higher economic development districts, lower initial
      capital investment of the CHCs, health services covered by health insurance,
      higher qualification of TCM physicians, provision of TCM health records and
      rehabilitation, and greater availability of herbal medicine. To achieve equal
      access to TCM services, policy makers should consider the socioeconomic
      differences and income groups, provide training for TCM physicians, build pathway
      to recruit senior TCM physicians, and cover more TCM therapies by health
      insurance. 

PMID- 23858518
TI  - Association between MTHFR gene polymorphisms, smoking, and the incidence of
      vascular dementia.
AB  - This study investigated the relationship between N5,N10-methylene tetrahydrofolic
      acid reductase (MTHFR) polymorphisms, smoking, and vascular dementia (VD).
      Polymerase chain reaction-restriction fragment length polymorphism analysis was
      used to analyze the frequency of the C/T polymorphism at position 677 of the
      MTHFR gene in 304 VD patients and 300 control patients with nondementia cerebral
      infarction. The CC, CT, and TT genotype frequencies of the MTHFR gene were
      43.42%, 32.57%, and 24.01%, respectively, in the VD group, and 50.67%, 32.00%,
      and 17.33%, respectively, in the control group. The T allele frequency was
      significantly higher in the VD group than in the control group (P < .05). Among
      patients who smoked, the relative risk of VD in patients with the TT genotype and
      T allele was higher than in the control group (P < .05). Therefore, the smoking
      group with the T allele has the highest risk of VD, and synergy appears to exist
      between the MTHFR gene polymorphisms and smoking in susceptibility to VD. 

PMID- 23858519
TI  - Universal coverage for primary health care is a wise investment: evidence from
      102 low- and middle-income countries.
AB  - We aimed to provide systemic, empirical evidence on the coverage expansion of
      primary health care (PHC) linking to good health in low- and middle-income
      countries. We conducted a pooled, cross-sectional analysis using the 2011 World
      Health Statistics for World Health Organization Member States at low- and middle
      income levels (n = 102). With life expectancy, infant mortality, and under-5
      mortality as health indicators, we examined the effect of service coverage rate
      using variables under 2 domains: health expenditure and PHC (public health
      provision, primary care access). Our results indicated that after controlling for
      gross national income per capita, higher total health expenditure as share of
      gross domestic product was associated with shorter life expectancy (beta = -0.99;
      P = .014), higher infant mortality (beta = 1.65; P = .155), and under-5 mortality
      (beta = 4.82; P = .020). Multivariate analysis showed higher coverage of public
      health services was significantly associated with improved population health.
      Making public health and primary care services accessible and be used by everyone
      is the wise means toward improved health. 

PMID- 23858520
TI  - Fish intake by adolescents is related to nutrient intake but not lifestyle
      factors.
AB  - Nutrition during adolescence influences long-term health outcomes. Consumption of
      fish has many health benefits, yet few studies have investigated associations
      between fish intake and nutrient intake and lifestyle factors in adolescents. A
      cross-sectional study utilizing 24-hour dietary recalls obtained by in-person
      interviews investigated relationships between fish intake and demographic
      characteristics, nutrient intake, and lifestyle factors among adolescents (mean
      age = 15.5 years). Height, weight, and self-administered survey data were
      collected from 839 high school students who took part in the 2000-2004 Hawaii
      Nutrition Education Needs Assessment survey. About 8.5% of the students consumed
      fish, based on estimated EPA (eicosapentaenoic acid) + DHA (docosahexaenoic acid)
      intakes. Adolescents who consumed fish had higher intake of protein, water, B
      vitamins, magnesium, selenium, and zinc but consumed more calories, fat,
      saturated fat, and sodium. Considering the school health program's potential to
      reach adolescents, more intensive school-based interventions can be directed to
      promote safe fish consumption and to encourage other positive lifestyle
      behaviors. 

PMID- 23858521
TI  - Meta-analysis of green tea drinking and the prevalence of gynecological tumors in
      women.
AB  - We performed a meta-analysis of the correlation between drinking green tea and
      the risk of female ovarian tumors. Related literature (2000-2010) was retrieved
      from PubMed, EMbase, CBMdisc, CNKI, and Wanfang databases. The relationship
      between the prevalence of ovarian cancer and drinking tea in cohort studies was
      explored. RevMan5.1.0 software was used for the meta-analysis. A total of 6 case
      control studies and cohort studies were included. A total of 9113 participants,
      3842 cases, and 5271 control cases were included in our analysis. Our analysis
      indicates that drinking green tea can significantly decrease the risk of ovarian
      cancer (odds ratio = 0.81; 95% confidence interval = 0.73-0.89; P < .0001).
      Further research is needed to explore the relationship between drinking green tea
      and the risk of ovarian tumor in different groups of people and with different
      tea types and dosages. 

PMID- 23858522
TI  - Thyroid function: comparison of women in late pregnancy with control women of
      reproductive age in regions of dietary iodine excess.
AB  - Three hundred pregnant women and 300 women of reproductive age (controls) were
      selected from regions with a dietary iodine excess to evaluate thyroid and
      autoimmune thyroid functions. Fasting morning urine and venous blood samples were
      collected. Urinary iodine concentration, serum free tri-iodothyronine (FT3), free
      thyroxine (FT4), sensitive thyroid stimulating hormone (sTSH), serum thyroid
      peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) levels were
      determined. Iodine levels were excessive in 83.7% of pregnant women and 80.7% of
      the control women. The former showed lower rates of total thyroid disease and
      subclinical hypothyroidism than the latter (21.7% vs 29.7%, P < 0.05; 19.7% vs
      27.3%, P < 0.05). The FT3 level, FT4 level, and TGAb positive rate of pregnant
      women were lower than that in the controls (P < 0.05). Thus, both excessive
      iodine intake and pregnancy can influence the thyroid and autoimmune thyroid
      functions of women. 

PMID- 23858523
TI  - Determinants of health-related quality of life in psoriasis patients in Malaysia.
AB  - Psoriasis is a chronic dermatological disorder that has a negative impact on
      quality of life (QoL). This hospital-based cross-sectional study determined
      factors associated with health-related QoL (HRQoL) impairment in adult psoriasis
      patients. HRQoL was assessed using the Dermatology Life Quality Index (DLQI).
      Disease severity was assessed using the Psoriasis Area and Severity Index (PASI).
      A total of 223 patients, aged 18 to 83 years, were recruited. For 67 (30%)
      patients, psoriasis had very large to extremely large effect on their life (DLQI
      score = 11-30). The median DLQI score was 7 (interquartile range = 7). Factors
      significantly associated with severe impact on HRQoL (DLQI >= 10) were disease
      severity, single status, working status, sports activities, nail dystrophy,
      exposed area involvement, itch, disturbed sleep, stress, and infection. The
      factor predictive of severe impact of psoriasis on HRQoL was disease severity. A
      holistic approach in the management, including psychosocial issues, is absolutely
      crucial for the optimal care of psoriasis patients. 

PMID- 23858524
TI  - Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications
      and long-term dosage evolution.
AB  - OBJECTIVE: To investigate the long-term dosage evolution and complication rate of
      intrathecal baclofen use in multiple sclerosis and spinal cord injury patients,
      based on a large population with a long follow-up. DESIGN: Retrospective data
      analysis. SETTING: Academic hospital. SUBJECTS: Patients with multiple sclerosis
      (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump
      implanted at the University Hospitals Leuven between 1988 and 2009. INTERVENTION:
      Medical records review of included patients in August 2010. MAIN MEASURES:
      Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after
      3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed
      using a mixed-effect linear model. RESULTS: In 130 patients with a mean follow-up
      of 63 months, comprising 797 pump years, 104 complications were recorded. This
      corresponds to a complication rate of 0.011 per month, equally divided among both
      groups. Seventy-eight of these complications were catheter related. The mean
      dosage of baclofen stabilizes two years after implantation at 323 ug/day in the
      multiple sclerosis population. In spinal cord injury patients the daily dose only
      stabilizes after five years at a significantly higher dosage (504 ug/day). No
      significant increase in dosage is seen in the long term. CONCLUSIONS: In multiple
      sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a
      complication rate of 1% per month. Complications are mainly due to catheter
      related problems (74%). The intrathecal baclofen dosage stabilizes in the long
      term, indicating that long-term tolerance, defined as progressive diminution of
      the susceptibility to the effects of a drug, is not present.

PMID- 23858525
TI  - A multicentre cluster-randomized controlled study to evaluate a train-the-trainer
      programme for implementing internal and external participation in medical
      rehabilitation.
AB  - OBJECTIVE: Evaluation of the effect of the train-the-trainer programme 'Fit for
      Shared Decision-Making' on internal (team) and external (patient) participation
      in medical rehabilitation from a patient and staff perspective. DESIGN: A
      multicentre, cluster-randomized controlled study. SETTING: Eleven medical
      rehabilitation clinics, divided into intervention and control groups. SUBJECTS: A
      staff and a patient survey were conducted pre- and post-intervention, plus a
      further patient survey six months later. INTERVENTION: Train-the-trainer
      programme 'Fit for Shared Decision-Making' for interprofessional settings. MAIN
      MEASURES: Each survey measured internal participation with a self-compiled six
      item scale (Internal Participation Scale, IPS), and external participation by
      means of a nine-item Shared Decision-Making Questionnaire (SDM-Q-9) for the
      patients and for healthcare professionals. RESULTS: Patient samples numbered 402
      for the pre-, 463 for the post-intervention data collection period and 461 six
      months after the intervention. Patients' appraisal of external participation
      (Fperiod x group (2) = 0.256, p=0.774, eta(2)=0.000) showed no change, whereas
      internal participation (Fperiod x group (2) = 3.785, p=0.023, eta(2)=0.007)
      showed a significant increase. A total of 195 healthcare professionals
      participated in the pre- and 168 in the post-intervention staff survey. Here
      external participation was significantly enhanced in the intervention group
      (F(period x group) (1) = 4.893, p=0.028, eta(2)=0.014). CONCLUSIONS: The train
      the-trainer approach can be recommended for implementing internal and external
      participation in interprofessional settings such as medical rehabilitation
      clinics. However, there is a need for more intensive staff training for internal
      participation and an additional intervention for patients to achieve success in
      all aspects.

PMID- 23858526
TI  - Clinical tools that measure sitting posture, seated postural control or
      functional abilities in children with motor impairments: a systematic review.
AB  - OBJECTIVE: To identify and critically appraise clinical measurement tools used to
      assess sitting posture, seated postural control or functional abilities for
      children with motor impairment who are candidates for seating interventions. DATA
      SOURCES: Searches were run in 15 electronic databases along with hand searching.
      The search included articles published in English to December 2011. REVIEW
      METHODS: Key terms included: posture, sitting, sitting posture, seated posture,
      seated postural control, sitting position, seating, wheelchair(s), outcome and
      assess(ment). The PRISMA statement was followed with inclusion criteria set a
      priori. Two reviewers independently screened titles, reviewed abstracts and
      identified full-text articles that met criteria. Data extraction included tool
      description and clinical utility. Two quality-rating scales were used to evaluate
      conduct of the studies and psychometric properties of the tools. RESULTS: Of the
      497 titles found in the search, 29 full-text articles met the inclusion criteria
      and 19 tools were identified. Tools represented all components of the
      International Classification of Functioning, Disability and Health for Children
      and Youth (ICF-CY), with emphasis on body structure and function and activity
      components. Evidence supporting reliability and validity varied, with small
      sample sizes influencing quality ratings. Evidence of the tools' reliability was
      more prevalent than evidence of the tools' validity. Only four tools reported on
      responsiveness, an important consideration for evaluating change. Little
      information on clinical utility was provided. CONCLUSION: Although a number of
      tools are available, evidence supporting their use for seating interventions is
      limited, as is the evidence supporting the strength of their measurement
      properties. Few tools address participation, environmental factors or the child's
      and family's perspective.

PMID- 23858527
TI  - State of the art: atopic dermatitis.

PMID- 23858528
TI  - Response from C. Clinton and D.P. Boyd.

PMID- 23858530
TI  - Retraction notice to "The effect of alendronate on the expression of osteopontin
      and osteoprotegerin in calcified aortic tissue of the rat".

PMID- 23858529
TI  - Cerebral hemodynamics and cognitive performance in bilateral asymptomatic carotid
      stenosis.

PMID- 23858531
TI  - [Vertebroplasty is still a good treatment!].

PMID- 23858534
TI  - Networking: Real connections.

PMID- 23858535
TI  - Trial and error.

PMID- 23858536
TI  - In the dark.

PMID- 23858537
TI  - Headline message.

PMID- 23858538
TI  - [Perinatal risk in younger siblings of premature births].

PMID- 23858539
TI  - Dilatation by Soehendra stent retriever is feasible and effective in multiple
      deployment of metallic stents to malignant hilar biliary strictures.
AB  - BACKGROUND/AIMS: The endoscopic management of malignant hilar biliary strictures
      using multiple metallic stents (MS) is technically demanding, in the initial
      deployment of MS and the recovery from MS occlusion with deployment of multiple
      plastic stents (PS). We evaluated the outcomes of the application of a Soehendra
      stent retriever (SSR) as a dilator of intractable strictures. METHODOLOGY: Fifty
      nine patients with malignant hilar biliary strictures had multiple MS inserted
      using a partial stent-in-stent procedure. When we encountered intractable
      strictures, we adopted SSR to dilate the stricture and the interstice of the MS.
      We evaluated the success rate of MS or PS deployment after SSR application and
      procedural complications. RESULTS: Five of 59 patients (8%) were subjected to SSR
      application for the initial MS deployment. MS were successfully deployed in all
      of these patients (100%). MS occlusion was noted in 27 patients. We applied SSR
      to seven patients (26%) for the deployment of multiple PS after MS occlusion. In
      five patients (71%), successful PS deployment was achieved after the SSR
      application. No complications related to dilatation using SSR occurred in any
      patient. CONCLUSIONS: SSR proved to be a potent dilator of difficult strictures
      in the management of malignant hilar biliary strictures.

PMID- 23858540
TI  - [Defibrillators in nursing homes?].

PMID- 23858541
TI  - [Patient safety and cell phones].

PMID- 23858542
TI  - [Reply: we want a debate on cell phone ban].

PMID- 23858543
TI  - [More departments should recruit a young education coordinating physician].

PMID- 23858544
TI  - [What do we know about the effects of user fees in general practice?].

PMID- 23858545
TI  - Impact of anticoagulation on outcomes in acute non-cirrhotic and non- malignant
      portal vein thrombosis: a retrospective observational study.
AB  - BACKGROUND/AIMS: No definitive evidence exists regarding the treatment of acute
      portal vein thrombosis (PVT). Treatment modalities that have been employed and
      investigated include conservative management, anticoagulation, thrombolysis and
      thrombectomy. This observational study examines the impact of anticoagulation on
      PVT. METHODOLOGY: The electronic radiology database was searched with keywords
      'portal vein' and 'thrombosis'. Relevant patient notes and imaging were reviewed
      to collect data from those with acute PVT. The primary end point was portal vein
      recanalisation. Secondary outcome measures were morbidity and the development of
      portal hypertension and its sequelae (including variceal bleeding). Data from
      patients with PVT in the context of cirrhosis, malignancy or liver transplant
      were excluded. RESULTS: Partial or complete recanalization of the portal vein
      occurred in 81.8% of anticoagulated patients and 37.5% of the non-treatment
      group. Five patients died, 1 following an intracranial haemorrhage whilst
      anticoagulated and another who was not treated and developed secondary small
      bowel ischaemia and peritonitis. The remaining 3 died from their underlying
      pathology. Late complications, such as varices and ascites occurred more
      frequently in the patients in whom the portal vein failed to recanalize (83.3%
      vs. 27.3%). CONCLUSIONS: Spontaneous resolution of acute portal vein thrombosis
      is uncommon. Early anticoagulation results in a higher rate of recanalisation
      with minimal associated morbidity when compared with no treatment.

PMID- 23858546
TI  - Expression of beta-adrenoceptors in human lower esophageal sphincter.
AB  - BACKGROUND/AIMS: Beta-adrenoceptor is considered to be an important modulator of
      smooth muscle function. It is widely present in the mammalian gastrointestinal
      tract and nervous system. The aim of this study was to explore the expression of
      1-adrenoceptors (beta1-AR, beta2-AR, beta3-AR) in sling fibers and clasp fibers
      from human lower esophageal sphincter (LES). METHODOLOGY: Sling and clasp fibers
      from the LES were obtained from patients undergoing esophagogastrectomy; 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 three subtypes of beta-adrenoceptors. RESULTS:
      Messenger RNA and protein for three subtypes of beta-adrenoceptors were all
      identified in the sling and clasp fibers of the LES. Expression was highest for
      beta3-AR, then beta1-AR and beta2-AR in decreasing levels. CONCLUSIONS: beta1-AR,
      beta2-AR, beta3-AR can be detected in human lower esophageal sphincter and
      contribute to LES function.

PMID- 23858547
TI  - Mon dieu! 30 years of HIV science.

PMID- 23858548
TI  - Roads less taken.

PMID- 23858549
TI  - Reply to Stadler: Combining network disassembly spectrometry with
      rheology/spectroscopy.

PMID- 23858550
TI  - The changing face of aid in Russia.

PMID- 23858551
TI  - Germany launches investigation into human trials scandal.

PMID- 23858552
TI  - The bad chaplain.

PMID- 23858554
TI  - Current world literature. Diseases of the pleura.

PMID- 23858555
TI  - Current world literature. Imaging.

PMID- 23858553
TI  - Re: Cognition in perimenopause: the effect of transition stage.

PMID- 23858556
TI  - Blood urea nitrogen is elevated in patients with non-alcoholic fatty liver
      disease.
AB  - BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) is strongly associated
      with many predictors of cardiovascular disease such as hypercholesterolemia,
      hypertriglyceridemia, insulin resistance, central obesity and the metabolic
      syndrome. Activation of renin-angiotensin-aldosterone system (RAAS) has been
      proved in patients with NAFLD. Blood urea nitrogen (BUN) elevation is a high risk
      factor and biomarker of RAAS activation of heart failure and coronary heart
      disease. The aim of the current study was to investigate BUN in patients with
      NAFLD. METHODOLOGY: BUN and creatinine (Cr) values of 85 patients with NAFLD and
      of 30 age- and gender-matched healthy individuals were compared prospectively.
      Liver/spleen ratios of computed tomography (CT) values were used to determine
      fatty liver and to evaluate fatty deposition. Alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) were employed to estimate inflammation. We
      analyzed the correlation between BUN and fatty deposition or inflammation.
      RESULTS: NAFLD patients had significantly higher BUN compared to the control
      cases (5.0353+/-1.1271 vs. 4.1263+/-1.0095 mmol/L; t=3.898, p<0.001). However,
      there was no difference in Cr (84.0941+/-14.4062 vs. 79.4667+/-16.7120 MUmol/L;
      t=1.45, p=0.15). BUN was negatively correlated with liver/spleen ratio of CT
      values (r=0.009, p=0.1974), ALT (r=-0.012, p=0.941) and AST (r=-0.009, p=0.592).
      CONCLUSIONS: We have shown for the first time in the literature, that patients
      with NAFLD have higher BUN. It may have prognostic value in NAFLD patients
      indicating a possible cardiovascular disease (CVD) risk increase.

PMID- 23858557
TI  - Folfox4 as a rescue chemotherapy for gemcitabine-refractory pancreatic cancer.
AB  - BACKGROUND/AIMS: This phase II study assessed the efficacy and safety of FOLFOX4
      as a rescue therapy in patients with gemcitabine-refractory pancreatic cancer.
      METHODOLOGY: The study included patients with advanced pancreatic cancer who had
      failed gemcitabine-based chemotherapy. FOLFOX4 was administered biweekly as
      follows: oxaliplatin, 85 mg/m2 as a 2-hour infusion (day 1); leucovorin, 200
      mg/m2/day as a 2-hour infusion (days 1 and 2); 5-fluorouracil, bolus 400
      mg/m2/day and 600 mg/m2/day as a 22-hour infusion (days 1 and 2). RESULTS: Forty
      four patients received a total of 264 cycles of chemotherapy. There was 1
      complete response (2.2%), 4 partial responses (9.1%), and 13 stable diseases
      (29.5%). The objective response rate was 11.4% and the tumor stabilization rate
      was 40.9%. The median time to progression was 9.9 weeks (95%CI: 8.2-11.5) and the
      median overall survival was 31.1 weeks (95%CI: 24.4-37.9). The common adverse
      events were hematologic toxicities: grade 3 or 4 neutropenia in 19 patients
      (43.2%), anemia in 9 patients (20.5%), and thrombocytopenia in 6 patients
      (13.5%). Grade 3 or 4 neuropathy occurred in 4 patients (9.1%). CONCLUSIONS: In
      gemcitabine-refractory pancreatic cancer, FOLFOX4 showed encouraging activity and
      was generally well-tolerated. However, careful attention needs to be paid to
      hematologic toxicities.

PMID- 23858558
TI  - A pilot study for preoperative concurrent chemoradiotherapy with S-1 and
      cisplatin for locally advanced gastric cancer.
AB  - BACKGROUND/AIMS: This study aims to determine the feasibility and effectiveness
      of concurrent chemoradiotherapy with the combination of S-1 and cisplatin in
      locally advanced gastric cancer. METHODOLOGY: Treatment-naive patients with
      locally advanced gastric cancer were enrolled. The patients received concurrent
      radiation (a total dose of 45 Gy: 25 fractions of 1.8 Gy) and chemotherapy. S-1
      was given orally at 60 mg/mg2 bid for 21 consecutive days with a resting period
      of 7 days. Cisplatin was given intravenously at 70 mg/m2 for 2 hours on day 1.
      The tumor response was evaluated 4-5 weeks after the completion of radiotherapy,
      and surgical resection was tried with curative intent if possible. RESULTS: Nine
      patients were enrolled, and all patients completed the initially planned
      concurrent chemoradiotherapy. Clinical response rate was 88.9% (8/9). Seven
      (77.8%) out of 9 patients underwent surgery, and an R0 resection was achieved in
      all of them. Pathological assessment of tumor regression after preoperative
      chemoradiotherapy showed total regression in 1 patient (14.3%), near total
      regression in 2 (28.6%), moderate regression in 3 (42.9%), and minimal regression
      in 1 (14.3%). Grade III/IV toxicity included anemia (44.4%), neutropenia (33.3%),
      and thrombocytopenia (22.2%). CONCLUSIONS: Preoperative concurrent
      chemoradiotherapy with S-1 and cisplatin is feasible and safe, and could offer an
      improved chance of tumor regression and curative resection in patients with
      locally advanced gastric cancer. Further trials with larger numbers of patients
      are warranted.

PMID- 23858559
TI  - Expression of p27Kip1 protein in gastric carcinoma.
AB  - BACKGROUND/AIMS: p27 protein resulted in the accumulation of cyclin E/cyclin
      dependent kinase 2/p27 ternary complexes inhibits gap1 to synthesis phase
      transition. Here, we have investigated the correlations, if any, between the
      expressions of p27 and p53, and proliferation cell nuclear antigen. METHODOLOGY:
      A retrospective study was performed on 75 cases of gastric cancer that had
      undergone surgical resection. Immunohistochemical staining was performed using
      the avidin-biotin-peroxidase complex technique method, with anti-p27 antibody,
      anti-p53 antibody and anti-proliferation cell nuclear antigen antibody. RESULTS:
      The rate of lymph node metastasis in the p27 negative cases was significantly
      higher than that in the p27 positive cases.The rate of tumor limited to the
      gastric wall in the p27 positive cases was significantly higher than-that in the
      p27 negative cases.The mean proliferation cell nuclear antigen index of the p27
      negative cases was significantly higher than that of the p27 positive cases. The
      survival rate of the p27 positive cases was significantly higher than that of the
      p27 negative cases. In Stage III cases, the survival rate of the p53 negative p27
      positive or p53 negative p27 negative cases was significantly higher than that of
      p53 positive p27 negative cases. CONCLUSIONS: p27 was correlated with lymph node
      metastasis, depth of invasion, and proliferative activity of gastric cancer.
      Immunoreactivity of combination of p53 and p27 was a useful predictive marker of
      prognosis of gastric cancer.

PMID- 23858560
TI  - Response to letter regarding article, "Cardiovascular risk of high- versus
      moderate-intensity aerobic exercise in coronary heart disease patients".

PMID- 23858561
TI  - Improved survival in kids a boost for ESRD therapy.

PMID- 23858562
TI  - Annular pancreas: unusual EUS finding in an adult patient with asymptomatic
      pancreatic hyperenzymemia.

PMID- 23858563
TI  - Enucleation of branch duct-IPMN in a transplant patient.

PMID- 23858564
TI  - CT angiography diagnosis of inferior pancreaticoduodenal artery aneurysm in
      association with celiac artery occlusion.

PMID- 23858565
TI  - Medications prescribed by non-VA providers. Final rule.
AB  - The Department of Veterans Affairs (VA) is amending its regulation concerning
      filling prescriptions written by non-VA providers for veterans of a period of war
      who are receiving increased pension because they are permanently housebound or in
      need of aid and attendance. This rulemaking revises the regulation to reflect the
      current statutory periods of war to ensure that eligible veterans engaged in
      current and future conflicts receive medications prescribed by non-VA physicians
      when appropriate for their care.

PMID- 23858566
TI  - Our community - our profession.

PMID- 23858567
TI  - Emergency animal diseases bulletin: rabies virus.

PMID- 23858568
TI  - Economics of the veterinary profession in Australia - pricing and charging for
      veterinary services.

PMID- 23858569
TI  - Diabetes and oral health. Abstracts of the 19th Annual International Conference
      of the University Diabetes Outreach Programme of the University of the West
      Indies and the University of Technology, Jamaica in collaboration with the
      Association of Public Dental Surgeons. March 21-23, 2013. Ocho Rios, Jamaica.

PMID- 23858570
TI  - Patient-centered medical homes improve care for adults with chronic conditions.
AB  - The success of health care reform implementation in 2014 partly depends on more
      efficient delivery of care to the millions of California residents eligible to
      gain insurance. Emerging evidence supports the effectiveness of the patient
      centered medical home (PCMH) as a potential model of care delivery, which
      improves health outcomes and reduces costs. Among other principles, PCMH entails
      receipt of care from a personal doctor, who coordinates the patient's care and
      develops an individualized treatment plan for the patient. These principles are
      particularly essential in delivery of care to those with chronic conditions who
      require more intensive care management. Using the 2009 California Health
      Interview Survey (CHIS 2009), this policy brief indicates that patients who
      reported meeting these fundamental PCMH principles were more likely to have
      visited the doctor and to have received flu shots, and they also had better
      communication with providers than those who did not report meeting these PCMH
      principles. The data also showed that uninsured individuals, Medi-Cal
      beneficiaries, those at or below 133% of the federal poverty level, Latinos, and
      Asian-Americans were less likely to report meeting all three PCMH principles.
      These findings highlight the population groups that would most benefit from the
      PCMH care delivery model, particularly Medi-Cal beneficiaries and those eligible
      for Covered California, the California health benefits exchange.

PMID- 23858571
TI  - [Research of autism spectrum disorders from child neurologist's angle].

PMID- 23858572
TI  - [A 7-year-old girl with psychomotor retardation and calcification in the basal
      ganglia].

PMID- 23858573
TI  - [Understanding and support for children with autism spectrum and developmental
      disorders--looking steadily at peaceful lives in adolescence].
AB  - For a long time autism spectrum and developmental disorders have not been well
      understood. Treatment and education for children with this disorders have been
      inappropriate in many ways. Although this fact was not obvious until many such
      children began to demonstrate secondary emotional disturbances including social
      withdrawal, social aggression, delinquency, domestic violence and momicide. This
      discourse describes advances in research and practice of clinical and psycho
      neurological for autism spectrum in recent years. In addition, I suggest policies
      and measures for therapeutic education that will avoid secondary symptoms
      allowing these individuals to conduct their lives in socially independent
      directions.

PMID- 23858574
TI  - [The role of neuroimaging in developmental social psychology].

PMID- 23858575
TI  - [Intervention to children with autism spectrum disorders--with the future of
      children in mind. Introductory remarks].

PMID- 23858576
TI  - [Psychological and pedagogical approach--preschool instruction for infant with
      high functioning pervasive developmental disorder].

PMID- 23858577
TI  - [Psychopharmacological interventions in autism spectrum disorders].

PMID- 23858578
TI  - [The parent training in Tottori Prefectural Rehabilitation Center for children
      with disabilities].

PMID- 23858579
TI  - [The support system for autism with severe behavioral problems].

PMID- 23858580
TI  - [The practice and problem of therapeutic agents for AD/HD].

PMID- 23858581
TI  - [Social problems of medicine in child neurologist].

PMID- 23858582
TI  - [Report of the 3rd meeting of Japanese child sleep association].

PMID- 23858583
TI  - [Neuroscience of attention deficit/hyperactivity disorder: special focus on the
      function of the inhibitory and reward systems].

PMID- 23858584
TI  - [Acute disseminated encephalomyelitis and pediatric multiple sclerosis: current
      states in Japan].

PMID- 23858585
TI  - [Botulinum toxin in the treatment of cerebral palsy--case conference].

PMID- 23858586
TI  - [Usefulness of the beta 2 microglobulin for the diagnosis of acute
      encephalopathy].

PMID- 23858587
TI  - [Future perspectives of the Japanese Society of Child Neurology].

PMID- 23858588
TI  - [A case of four-year-old boy with cataract and hypotonia].

PMID- 23858589
TI  - [No To Hattatsu: past, present and future].

PMID- 23858590
TI  - [Advances in elucidating the pathophysiology and targeting therapy to treat
      Niemann-Pick type C disease].

PMID- 23858591
TI  - [Medical services directed at children with neurodevelopmental disabilities-
      current knowledge and prospect].

PMID- 23858592
TI  - [Comments from the NPO activities for the child neurologists].

PMID- 23858593
TI  - [Progress in the diagnoses and treatment for hereditary neurological and muscular
      disorders. Introductory remarks].

PMID- 23858594
TI  - [The efficacy of enzyme replacement therapy in pompe disease and secondary
      pathology in pompe muscle "excessive autophagy" which is relevant to the therapy
      resistance].

PMID- 23858595
TI  - [Exon skipping therapy for Duchenne muscular dystrophy: outcome of preclinical
      study and prospective for clinical study].

PMID- 23858596
TI  - [Diagnosis and treatment of mitochondrial myopathy--update review].

PMID- 23858597
TI  - [Construction of a research resource repository and molecular genetic study for
      mental retardation].

PMID- 23858598
TI  - [Chemical chaperone therapy:a new molecular therapeutic approach to neurogenetic
      diseases].

PMID- 23858599
TI  - [Revolutionary progress and clinical application of digital karyotyping by array
      CGH].

PMID- 23858600
TI  - [Current problems of treatment for infantile spasms].

PMID- 23858601
TI  - [Guideline for diagnosis and intervention of specific developmental disorders].

PMID- 23858602
TI  - [Advances in the research on neurocutaneous syndromes: neurofibromatosis type 1
      and tuberous sclerosis complex].

PMID- 23858603
TI  - [Globalization of child neurology].

PMID- 23858604
TI  - [A 4-year-old boy showing gait disturbance].

PMID- 23858605
TI  - [Bench to bedside, tertiary centres to developing world --"tailoring" best
      available neuroprotection in high and low resource settings].
AB  - Neuroprotection following brain injury has been a top priority in neuroscience
      since the Hippocratic era. However, of hundreds of "experimentally
      neuroprotective treatments", currently only hypothermia is clinically available.
      Interpretation of bench-work may have to account for the variation in
      developmental stages and types of injury. For example GABAergic stimulators have
      been used to reduce cerebral energy consumption; recent studies suggested the
      paradoxical excitation of premature neurons following GABAergic stimuli because
      of the high intracellular chloride concentration during the perinatal period.
      Even for hypothermia, many questions remain unanswered:selective-head cooling
      following perinatal hypoxia-ischemia appeared rather deleterious for infants with
      the most severe encephalopathy or low birth-weight. In a piglet model, different
      cooling levels provided differential regional brain protection:35 degrees C was
      optimal for deep-grey-matter whereas the cortical-grey-matter was better
      protected at 33 degrees C, suggesting that a single cooling level may not be
      equally optimal for the entire brain. Another experimental study used magnetic
      resonance spectroscopy to demonstrate that the more severe the acute event was,
      the shorter the therapeutic time window was, explaining the lower effectiveness
      of neuroprotection following the most severe hypoxia-ischemia. Another suggestion
      from our translational research was the dependence of cerebral temperatures on
      body weight under selective-head cooling:the smaller the body weight, the lower
      the brain temperature, presumably because of the larger surface area to brain
      volume ratio in small subjects. Thus translational research is essential to
      achieve "tailored" treatments, that address for individual and regional cerebral
      conditions. Although therapeutic options have become available in the tertiary
      centre settings, neuroprotection should not remain an expensive treatment only
      available in rich countries. We have recently developed a cooling system that can
      maintain stable hypothermia over 24 hours without an electric supply.
      Experimental studies to optimise high-tech cooling need to run in parallel with
      studies to increase the distribution of these treatments worldwide.

PMID- 23858606
TI  - [Developmental changes in reading ability of Japanese elementary school children-
      analysis of 4 kana reading tasks].
AB  - Five hundred and twenty-eight Japanese elementary school children aged from 6
      (Grade 1) to 12 (Grade 6) were tested for their abilities to read Hiragana
      characters, words, and short sentences. They were typically developing children
      whom the classroom teachers judged to have no problems with reading and writing
      in Japanese. Each child was asked to read four tasks which were written in
      Hiragana script: single mora reading task, four syllable non-word reading task,
      four syllable word reading task, and short sentence reading task. The total
      articulation time for reading and performance in terms of accuracy were measured
      for each task. Developmental changes in these variables were evaluated. The
      articulation time was significantly longer for the first graders, and it
      gradually shortened as they moved through to the upper grades in all tasks. The
      articulation time reached a plateau in the 4th grade for the four syllable word
      and short sentence reading tasks, while it did so for the single mora and four
      syllable non-word reading tasks in the 5th grade. The articulation times for the
      four syllable word and short sentence reading tasks correlated strongly. There
      were very few clear errors for all tasks, and the number of such errors
      significantly changed between the school grades only for the single mora and four
      syllable word reading tasks. It was noted that more than half of the children
      read the beginning portion of the word or phrase twice or more, in order to read
      it accurately, and developmental changes were also seen in this pattern of
      reading. This study revealed that the combination of these reading tasks may
      function as a screening test for reading disorders such as developmental dyslexia
      in children below the age of ten or eleven years old.

PMID- 23858607
TI  - [Continuous electroencephalogram monitoring in a pediatric intensive care unit].
AB  - This study sought to determine the effectiveness of continuous
      electroencephalogram (cEEG) monitoring for predicting neurological outcome among
      children with status epilepticus or altered consciousness in a pediatric
      intensive care unit (PICU). We detected nonconvulsive seizures and evaluated the
      relationship between electroencephalogram features and neurological outcome.
      Nonconvulsive seizures were detected in nearly 30% of the 79 patients who
      underwent cEEG monitoring, a rate that was similar to those seen in studies of
      adults. All patients who showed low voltage readings (< or = 10 micro V) at the
      time cEEG monitoring was started had poor neurological outcome (any changes in
      Pediatric Cerebral Performance Category Scale). Among patients who did not show
      low voltage readings, those who exhibited nonconvulsive seizures were more likely
      to have poor neurological outcome than those who did not. In a PICU, cEEG
      monitoring can help to predict neurological outcome in the early stage of
      treatment for children with status epilepticus or altered consciousness.

PMID- 23858608
TI  - [Developmental changes in the kiddie continuous performance test and its
      appropriate age for application].
AB  - The Kiddie Continuous Performance Test (K-CPT) was produced by Conners for
      children in age from 4 to 5 years. This study attempted to examine the
      developmental changes and gender differences of this test in children from
      preschool to adolescence, to verify its appropriate age range for application,
      and also to obtain a norm for clinical applications. K-CPT was administered to
      327 healthy participants from 4 to 18 years of age. Participants were divided
      into 7 age groups. The performances were examined in 6 measures: the total number
      of omission errors (OE), the total number of commission errors (CE), the mean hit
      reaction time (HRT), the hit reaction time standard error (HRTSE), perceptual
      sensitivity (d') and response style (beta). All measures showed significant
      developmental changes. OE and beta showed floor effects around 10 years. Such
      measures as CE, HRT, HRTSE and d' showed significant developmental changes until
      adolescence. The effect of gender was found in performances in OE, CE, d' and
      beta. Male participants made more errors and showed less favorable perceptual
      sensitivity than did female participants. Results suggested that K-CPT would be
      appropriate for use with preschoolers and school-aged children. Findings also
      suggested that it is a potential diagnostic tool in children with developmental
      disorders.

PMID- 23858609
TI  - [Study of an efficacy and a pharmacokinetics of intranasal midazolam for status
      epilepticus on childhood epilepsy].
AB  - We reviewed the efficacy and a pharmacokinetics of intranasal midazolam (MDL) for
      status epilepticus in childhood epilepsies. This trial was planned for the
      patients who developed status epilepticus at least once in the past and had no
      responses with diazepam. Intranasal midazolam was proved to be effective
      (complete remission;65%), rapidly (an average time to stop seizures; 5.7 min) and
      safe with no adverse effects including respiratory depression with this dosage
      (an average of 0.26 mg/kg). In patients whose longitudinal concentrations of MDL
      in the blood were measured, MDL level was increased rapidly within five minutes
      after nasal application. Intranasal MDL is useful as a simple and safe method in
      the child emergency situation.

PMID- 23858610
TI  - [Assessment of joint attention skill in at-risk infants during follow-up
      outpatient examination].
AB  - We assessed the joint attention skill of infants by a novel method. One hundred
      eighty infants who were discharged from the NICU of Teikyo University Hospital
      and subsequently brought to the outpatient clinic for follow-up examinations
      between 6 and 12 months of corrected age (297 examinations in total) were entered
      into the study. Infant were sitting on the mother's knees facing the examiner.
      After confirming the infant's visual axis to the examiner's eyes, the examiner
      looked at blocks held in the infant's visual field. When the infant looked at the
      blocks by perceiving the examiner's gaze, the infant was judged to have joint
      attention skill. Then, when the infant looked at the examiner again, the attitude
      was estimated as an action for reconfirmation. Sixty percent of the infants at 6
      months of age showed joint attention skill, and more than 90 % of infants showed
      this skill at 9 months of age. At 6 months of age, boys showed that skill
      significantly more frequently than girls. This new method is very easy to
      perform, uses only small blocks and can be completed within a few minutes.
      Therefore, we considered this new method useful for the assessment of joint
      attention skill in infants during periodic outpatient health clinic examination.

PMID- 23858611
TI  - [A boy with hypomyelination with atrophy of the basal ganglia and cerebellum].
AB  - Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a
      rare leukoencephalopathy first described by van der Knaap in 2002. Diffuse
      cerebral hypomyelination and atrophy of the basal ganglia and cerebellum
      characterize H-ABC. We report a 9-year-old Japanese boy with H-ABC who had been
      suspected to have Pelizaeus Merzbacher disease. Brain MRI revealed delayed
      myelination, however, no other remarkable abnormal laboratory findings were
      found. PLP1 gene mutation was not detected and he had no nystagmus. He was
      diagnosed as having H-ABC at the age of 8 years because of supratentorial
      hypomyelination and progressive atrophy of the basal ganglia and cerebellum on
      the follow-up MRI. This boy's condition was clinically more severe than those
      with other reported patients with H-ABC.

PMID- 23858612
TI  - [High dose of enzyme replacement therapy was successful for the pulmonary
      involvement in a case of type 2 Gaucher disease].
AB  - Pulmonary involvement is a serious complication in Gaucher disease, as is
      neuronopathic involvement. Few reports are available, however, on the frequency,
      clinical course and therapy for pulmonary involvement in patients with Gaucher
      disease. We report a case of type 2 Gaucher disease with severe
      hepatosplenomegaly, anemia, hypertonia, and psychomotor retardation. The
      diagnosis of Gaucher disease was confirmed by the presence of Gaucher cells in
      bone marrow and low serum beta-glucocerebrosidase activity (patient, 0.8;
      control, 4.1-9.7 nmol/mg.protein/hr) at the age of 1 year. The patient's genotype
      is L444P/unknown. Enzyme replacement therapy (ERT) with intravenous imiglucerase
      at 78 U/kg/2weeks was started, and hepatosplenomegaly and laboratory
      abnormalities were markedly improved after 6 months of therapy. After 8 months of
      therapy, respiratory impairment appeared together with a decrease of tidal volume
      and low SpO2 during sleep. Serum acid phosphatase and angiotensin converting
      enzyme levels mildly increased, and radiological findings showed bilateral ground
      glass appearance without signs of respiratory infection. With the diagnosis of
      progressive pulmonary involvement in Gaucher disease, we increased the dosage of
      imiglucerase from 50 to 75 U/kg/2 weeks. After a month, respiratory symptoms and
      CT findings of ground-glass appearance remarkably improved, but interlobular
      septal and intralobular interstitial thickening persisted. The maximum permitted
      dosage of imiglucerase in Japan is 60 U/kg/2 weeks. Based on our experience with
      this case, we propose that a higher ERT dosage would be uselul for serious
      pulmonary involvement.

PMID- 23858613
TI  - [A case of acute encephalitis with refractory, repetitive partial seizures
      requiring a high concentration of isoflurane to suppress the seizures and showing
      abnormal findings in the bilateral thalamus on MRI during the convalescent
      period].
AB  - We report a patient with acute encephalitis with refractory, repetitive partial
      seizures requiring a high concentration of isoflurane to suppress the seizures
      and showing rare abnormal findings in the bilateral thalamus on MRI during the
      convalescent period. A five-year-old boy was admitted to our hospital because of
      fever and convulsions. Shortly after admission, convulsions became frequent and
      disturbance of consciousness became apparent. Abnormal findings on
      electroencephalogram indicated encephalitis. Convulsions could not be suppressed
      by any intravenous anticonvulsants including barbiturates. Inhalational
      anticonvulsant treatment with isoflurane was performed, but it was ineffective at
      a low concentration. A high concentration of isoflurane was needed to suppress
      convulsions. Since a high concentration of isoflurane induces hypotension,
      various drugs to increase blood pressure were also administered. Convulsions
      reappeared during withdrawal of isoflurane. Finally isoflurane was withdrawn
      without inducing status epilepticus by administration of intravenous and oral
      anticonvulsants during the withdrawal process. Neurological sequelae were very
      severe and there are no anticonvulsants that have effectively suppressed the
      convulsions to date. MRI during the convalescent period showed high-intensity
      signal changes on fluid-attenuated inversion recovery, diffusion-weighted image
      and T2-weighted image in the bilateral thalamus. But it is uncertain whether
      these changes were the cause of this disorder.

PMID- 23858615
TI  - [A case of non-herpetic acute limbic encephalitis associated with influenza A
      infection].

PMID- 23858614
TI  - [A case of bipolar I disorder with autistic disorder showing "waiting-for
      instruction" as a depressive symptom].
AB  - We have experienced a case of bipolor I disorder complicated by mental
      retardation and autistic disorder. Acquired daily life activities such as eating,
      clothing and toileting without assistance were gradually lost during depressive
      periods, which was consistent with the previous reports. Before losing daily life
      skills, the patient could no longer perform daily life activities without
      consecutive instructions. This "waiting-for-instruction" behavior may be an early
      diagnostic key for major depressive episode in mentally-retarded children and
      adolescents.

PMID- 23858616
TI  - [Perimesencephalic nonaneurysmal subarachnoid hemorrhage caused by exercise--a
      case of a 6-year-old girl].

PMID- 23858617
TI  - Emerging concepts in pediatric bone disease.

PMID- 23858618
TI  - Nutritional rickets: pathogenesis and prevention.
AB  - Nutritional rickets remains a public health concern in many areas of the world
      despite cheap and effective means of preventing the disease. The roles of vitamin
      D deficiency, low dietary calcium intakes and the interrelationships between the
      two in the pathogenesis of the disease are discussed. It is now recognized that
      vitamin D deficiency in the pregnant and lactating mother predisposes to the
      development of rickets in the breastfed infant, and that cultural and social
      factors are important in the pathogenesis of the disease during the adolescent
      growth spurt. Prevention of rickets is dependent on the awareness of the medical
      profession and the general public of the need to ensure adequate intakes of
      vitamin D in at-risk populations, and of the importance of increasing dietary
      intakes of calcium using locally available and inexpensive foods in communities
      in which dietary calcium deficiency rickets is prevalent.

PMID- 23858619
TI  - Vitamin D action: lessons from VDR and Cyp27b1 null mice.
AB  - Even one century after its discovery, there are still many gaps in the
      understanding of the vitamin D endocrine system. Inactivation of the vitamin D
      receptor (VDR) or the enzymes metabolizing its ligand (especially Cyp27bl) in
      mice has clearly demonstrated that the active form of vitamin D [1,25(OH)2D] is
      essential to stimulate calcium absorption in the gut during normal/low calcium
      intake, and as a consequence, that 1,25(OH)2D is required to maintain normal
      serum calcium, bone and growth plate homeostasis. These findings have resulted in
      clear clinical guidelines for the treatment of vitamin D-related bone diseases of
      infants, children and adults. Tissue-specific VDR or Cyp27b1 deletion in mice has
      also proven to be useful to define the precise role of 1,25(OH)2D action in cells
      belonging to the intestine, bone, growth plate and also to many non-classical
      target tissues. Indeed, experimental findings show that 1,25(OH)2D has numerous
      extraskeletal effects, and observational studies in man demonstrate that
      disturbances in the vitamin D pathway are associated with major human diseases
      such as cancer, infections, autoimmune diseases, cardiovascular and metabolic
      diseases, muscle function, reproduction and neurocognitive disorders. We will
      compare the findings in VDR- and Cyp27bi-null mice with findings in man to
      elucidate what is presently understood of the vitamin D endocrine system and to
      identify the still outstanding questions.

PMID- 23858621
TI  - Hypophosphatasia.
AB  - Hypophosphatasia (HPP) is a rare, inherited, potentially life-threatening
      metabolic disorder that arises from loss-of-function mutations in the gene that
      encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). As a
      result of these mutations (as many as 260 genetic mutations have been associated
      with HPP), patients have disordered bone mineralization leading to rickets,
      osteomalacia, fractures and other skeletal abnormalities as well as other
      systemic complications such as seizures, respiratory compromise, dental
      anomalies, nephrocalcinosis and/or weakness and chronic pain. HPP may appear
      across the age spectrum, from in utero, to infancy, childhood, adolescence and/or
      adulthood. More severe cases tend to be seen in utero and infancy, and in these
      instances, mortality may be as high as 50%. In surviving or older patients,
      disability and poor quality of life may be seen. Based on clinical presentation,
      HPP can be mistakenly diagnosed as other skeletal diseases, but a low alkaline
      phosphatase is an important, distinguishing sign of this condition. While
      patients with HPP may benefit from supportive measures, at the present time,
      there is no approved specific therapy for HPP.

PMID- 23858622
TI  - Fibrous dysplasia.
AB  - Fibrous dysplasia is a developmental abnormality of bone that is characterized by
      a highly disorganized mixture of immature fibrous tissue and fragments of
      immature trabecular bone. Fibrous dysplasia may arise as a single, discrete
      (monostotic) lesion or can occur with a more widespread distribution with
      multiple lesions that affect many bones (oligo- or polyostotic). Fibrous
      dysplasia is usually an isolated skeletal finding but can sometimes occur as a
      component of a multisystem developmental disorder known as McCune-Albright
      syndrome (MAS) that is also associated with endocrine hyperfunction (e.g.
      precocious puberty) and caf au lait cutaneous macules. The identification of
      activating mutations in GNAS in a subset of human GH-secreting pituitary tumors
      and autonomously functioning human thyroid tumors provided the initial basis for
      understanding the molecular pathophysiology of McCune-Albright syndrome and
      fibrous dysplasia. These observations led to the concept that activating
      mutations of the GNAS gene convert it into a putative oncogene referred to as gsp
      (Gsa or Gas). The classic radiographic feature of fibrous dysplasia is a hazy,
      radiolucent, or ground-glass, pattern resulting from the defective mineralization
      of immature dysplastic bone; it is usually strikingly different from the
      radiographic appearance of normal bone, calcified cartilage, or soft tissue. The
      surgical approach to fibrous dysplasia should in general be conservative. Recent
      research suggests that the WntlB-catenin pathway may play a role in fibrous
      dysplasia as patients with activating GNAS mutations specifically showed that Gas
      mutations activated Wnt/B-catenin signaling. Thus inhibition of 8-catenin
      signaling or silencing GNAS alleles that encode constitutively active Gsa
      molecules in fibrous dysplasia and McCune-Albright syndrome offer potential
      therapeutic promise and deserve further study. In summary fibrous dysplasia is a
      developmental abnormality of bone with a known molecular etiology; Further
      knowledge about the molecular pathology of fibrous dysplasia may lead to improved
      conservative therapies in the near future.

PMID- 23858620
TI  - The changing face of hypophosphatemic disorders in the FGF-23 era.
AB  - In the past decade, research in genetic disorders of hypophosphatemia has
      significantly expanded our understanding of phosphate metabolism. X-linked
      hypophosphatemia (XLH) is the most common inherited form of rickets due to renal
      phosphate wasting. Recent understanding of the mechanisms of disease and role of
      fibroblast growth factor 23 (FGF-23) in XLH and other hypophosphatemic disorders
      have opened new potential therapeutic avenues. We will discuss the current
      standard of treatment for XLH as well as promising future directions under study.

PMID- 23858623
TI  - Osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI), an inherited skeletal disorder characterized by low
      bone mass, bone fragility, and often short stature. The clinical severity varies
      widely from being nearly asymptomatic with a mild predisposition to fractures,
      normal stature and normal lifespan being to profoundly disabling and even lethal.
      Extra skeletal manifestations may include blue-grey sclera and dental
      abnormalities. Initially, the classification of OI into four types was based on
      clinical findings, but more recently additional types OI (types V-XI) have been
      ascertained, based on the identification of different mutations. While this
      classification is somewhat controversial, it is described in this article. The
      treatment of patients with OI is based on the nature and severity of symptoms.
      The goal of therapy is to prevent fractures and disability, improve function and
      quality of life. A multidisciplinary approach is needed, and treatment options
      include medication such as bisphosphonates, surgery, and rehabilitation.
      Investigations continue to explore gene and cell therapies that may be developed
      in the future.

PMID- 23858624
TI  - Skeletal abnormalities in lysosomal storage diseases.
AB  - Many of the lysosomal storage diseases (LSDs) have skeletal abnormalities causing
      significant morbidity. Dysostosis multiplex describes a constellation of
      radiographic skeletal findings that are helpful in diagnosing many of the LSDs,
      particularly the mucopolysaccharidoses (MPS). This review discusses the clinical
      and radiographic skeletal manifestations of various LSDs with an emphasis on
      disorders that have significant skeletal involvement (eg, MPS disorders,
      mucolipidosis type II and Iil, Gaucher). Enzyme replacement therapy (ERT) for
      several of the LSDs has been beneficial for many of the clinical manifestations,
      but efficacy with regard to the skeletal abnormalities is not as obvious. As the
      pathophysiology of the skeletal abnormalities associated with LSDs becomes better
      elucidated, investigators will likely develop improved therapies to specifically
      target bone and alleviate the skeletal problems.

PMID- 23858625
TI  - Bone lessons from Marfan syndrome and related disorders: fibrillin, TGF-B and BMP
      at the balance of too long and too short.
AB  - The extracellular matrix (ECM) is a complex entity with structural proteins (such
      as fibrillins, collagen, elastin), ground substance (proteoglycans), modifying
      enzymes (ADAMTS, PLOD, lysyloxidases (LOX)) and cytokines that regulate
      morphogenesis, growth, homeostasis and repair (transforming growth factor-beta
      [TGF-beta], bone morphogenic protein [BMP]). Over the last decade, the intimate
      relationship between structural proteins and these growth factors has emerged.
      The study of the extracellular matrix in human conditions and relevant mouse
      models is gradually unmasking the key role of these structural molecules in the
      regulation of the bio-availability of these growth factors. Major progress has
      been made in the study of the cardiovascular system (1) and the first clues in
      the skeletal system have emerged. (2) In this review, we will discuss the
      clinical, molecular, and pathogenic aspects of Marfan syndrome, Loeys-Dietz
      syndrome and related disorders with emphasis on the role of fibrillins and TGF
      beta.

PMID- 23858626
TI  - Causes of secondary pediatric osteoporosis.
AB  - Secondary osteoporosis is increasingly observed in both adult and pediatric
      patients affected by many heterogeneous diseases. Most forms of secondary
      osteoporosis derive from one or more of the following causes: malnutrition,
      malabsorption, immobilization and/or reduced mechanical load, vitamin D
      deficiency, chronic inflammation, hormonal derangements, and chronic use of
      glucocorticoids and other drugs. Considering the lack of symptoms in the early
      phases, both the risk and the presence of secondary osteoporosis tend to be
      underestimated, and as a consequence, appropriate prevention/treatment measures
      are often delayed or not taken at all. Failure to accumulate an appropriate bone
      mass for gender and age or to build an architecturally "strong" bone must always
      be suspected when a child or adolescent presents with frequent and/or low-trauma
      fractures, chronic bone pain, or an incidental finding of "osteopenia" on plain X
      rays. Known risk factors must always be considered.

PMID- 23858628
TI  - Dental act and insults to oral health.

PMID- 23858629
TI  - Understanding head and neck cancers.

PMID- 23858627
TI  - Fibrodysplasia ossificans progressiva: diagnosis, management, and therapeutic
      horizons.
AB  - Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic
      condition characterized by congenital malformations of the great toes and
      progressive heterotopic endochondral ossification (HEO) which is the most
      catastrophic of HEO disorders in humans. Flare-ups of FOP are episodic;
      immobility is cumulative. Heterozygous activating mutations in activin receptor
      IA/activin-like kinase-2 (ACVRI/ ALK2), a bone morphogenetic protein (BMP) type I
      receptor, exist in all sporadic and familial cases of FOP. The discovery of the
      FOP gene established a critical milestone in our understanding of FOP, and
      revealed a highly conserved therapeutic target in the BMP signaling pathway. This
      discovery has advanced efforts to develop novel therapies for this disabling
      disorder of tissue metamorphosis. While effective treatment of FOP will likely be
      based on interventions that modulate overactive ACVR1/ALK2 signaling, or that
      specifically block postnatal HEO, current management is focused on early
      diagnosis, assiduous avoidance of injury or iatrogenic harm, symptomatic
      amelioration of painful flare-ups, and optimization of residual function.

PMID- 23858630
TI  - The dentist's role within the multi-disciplinary team maintaining quality of life
      for oral cancer patients in light of recent advances in radiotherapy.
AB  - Every year in Ireland over 400 people are diagnosed with head and neck cancer.
      Oral cancer, a specific type of head and neck cancer, is usually treated with
      surgery and often requires radiotherapy (RT). However, side effects of RT
      treatment, which include mucositis, xerostomia, radiation caries, trismus and
      osteoradionecrosis, can seriously compromise a patient's quality of life.
      Treatment for oral cancer patients is managed in a multidisciplinary team.
      General dental practitioners (GDPs), consultant/specialist dentists and oral
      maxillofacial surgeons play an important role in these patients' care. Recent
      advances in the delivery of RT have not only improved locoregional control and
      survival rates, but have also reduced the incidence and severity of RT-associated
      side effects; however, no mode of RT delivery has successfully eliminated side
      effects. The role of dentists is essential in maintaining oral health and all
      patients should be dentally screened prior to commencing RT. Recent reports have
      attempted to standardise the quality of care for the oral cancer patient and have
      highlighted the significance of the role of the GDP. Despite the advancements in
      RT delivery, the dental team is still faced with a number of challenges,
      including the high number of patients lost to follow-up dental care, lack of an
      effective treatment for xerostomia, poor patient compliance, and a lack of
      standardised guidelines and funding. Addressing these challenges will involve
      increased communication between all members of the multidisciplinary team and
      increased involvement of the GDP, thereby ensuring that dental care continues to
      evolve concurrently with new methods of RT delivery.

PMID- 23858631
TI  - Business and finance - planning for success.

PMID- 23858632
TI  - [Cost effectiveness and dental caries prevention].

PMID- 23858633
TI  - [Requirements regarding health records: transfer or copy].
AB  - Dutch law requires every healthcare provider, which obviously includes dentists,
      to maintain health records. Most of the rules governing the health record
      requirement are in the Law of Agreement to Medical Treatment (WGBO). And, as is
      often the case with the law, interpretation is left to the (disciplinary)judge.
      There is, in fact, a considerable amount of legal precedent concerning what
      information belongs in the health record. It is not uncommon for a dentist to be
      on the losing side in a legal proceeding because his defence is not supported by
      the health record. And if it becomes clear that (a portion of) the health record
      has been destroyed, despite the legal requirement to maintain records, in this
      too the dentist can count on little sympathy from the judge. In a recent
      judgment, the Central Disciplinary Committee was more severe than ever- with far
      reaching consequences for the relevant dentist.

PMID- 23858634
TI  - [Spontaneous loss of permanent teeth in children is never innocent].
AB  - A 13-year-old patient spontaneously lost tooth 47. In addition, he had for
      several weeks experienced numbness of the lower lip and the chin on the right
      side, fatigue, weakness, loss of appetite, and weight loss. After extensive
      investigation he seemed to be suffering from a Burkitt lymphoma. Spontaneous loss
      of permanent teeth in children has an extensive differential diagnosis. Dentists
      should be familiar with this differential diagnosis as all possible diagnoses are
      related to serious pathologies. The differential diagnosis includes infectious,
      metabolic, naplastic, and odontogenic causes. Systematic history taking, physical
      examination and laboratory investigations will lead to a proper diagnosis.

PMID- 23858635
TI  - [Oral medicine 7: white lesions of the oral mucosa].
AB  - White lesions of the oral mucosa may be due to highly diverse disorders. Most of
      these disorders are benign but some may be a malignant or premalignant condition.
      The disease is often confined to the oral mucosa. There are also disorders which
      are accompanied by skin disorders or systemic diseases. Many white oral mucosa
      disorders have such characteristic clinical aspects that a diagnosis can be made
      on clinical grounds only. When the clinical diagnosis is not clear,
      histopathological examination is carried out. Treatment depends on the
      histological diagnosis. In some cases, treatment is not necessary while in other
      cases, treatment is not possible since an effective treatment is not available.
      Potentially malignant disorders are treated.

PMID- 23858636
TI  - [Dentistry and healthcare legislation 3: informed consent].
AB  - The relationship between a dentist and his patient is based on trust. The
      principle of informed consent contributes to the quality of that relationship of
      trust. According to the professional standards for such a relationship, it is up
      to the dentist to make sure that the patient is well informed. Reliable
      information is necessary if the patient is to be in a position to give his or her
      consent for treatment. The Dutch Law of Agreement to Medical Treatment (WGBO)
      provides aframework for informed consent. Disciplinary judges establish the scope
      and if necessary the limits. It is clear that, among other things, not defining
      the risks beforehand can be the basis for a (disciplinary) complaint. Determining
      the requirements of informed consent calls for familiarity with the law and
      communication skills. Programmes in dental education ought to devote more
      attention to this issue.

PMID- 23858637
TI  - [Systemic reactions to orally applied metal alloys].
AB  - Orally applied metal alloys can cause undesirable physical effects. A distinction
      needs to be made in this respect between local and systemic reactions and toxic
      and immunological reactions. A case is presented which illustrates this problem.
      In this case, the application of orthodontic appliances was probably the trigger
      for an exacerbation of nickel allergy. The oral exposure to nickel resulted in
      hand eczema. The patient was also exposed to nickel by single-unit fixed dental
      prostheses, a removable dental prosthesis, and food, as a result of which removal
      of the orthodontic appliances did not result in complete healing. Therefore, the
      single-unit fixed dental prostheses also had to be removed and food had to be
      prepared henceforward in nickel free pans.

PMID- 23858638
TI  - [Contact wear related to single- and multi-unit dental prostheses].
AB  - Occlusal surfaces of teeth and restorations wear by repeated antagonistic
      contact. Two-body wear is the result of direct contact between occlusal surfaces.
      In cases of three-body wear, food is found between antagonistic teeth. Contact
      wear is expressed predominantly by abrasion and material fatigue. Erosion is a
      type of wear which does not involve direct antagonistic contact. Qualitative
      methods exist for registering occlusal tooth wear. Wear of restorations can be
      measured using casts. An obvious method for comparing rates of wear of
      restorative materials is laboratory research. This method has demonstrated that
      the wear rates of composite and enamel are similar. Cast metals and in particular
      ceramic wear less than enamel. The relation between oral factors and the rate of
      tooth wear is not always clear. Wellpolished surfaces of restorations wear less
      quickly and have less effect on the wearing of antagonistic teeth than rougher
      restoration surfaces.

PMID- 23858639
TI  - Do invasive species perform better in their new ranges?
AB  - A fundamental assumption in invasion biology is that most invasive species
      exhibit enhanced performance in their introduced range relative to their home
      ranges. This idea has given rise to numerous hypotheses explaining "invasion
      success" by virtue of altered ecological and evolutionary pressures. There are
      surprisingly few data, however, testing the underlying assumption that the
      performance of introduced populations, including organism size, reproductive
      output, and abundance, is enhanced in their introduced compared to their native
      range. Here, we combined data from published studies to test this hypothesis for
      26 plant and 27 animal species that are considered to be invasive. On average,
      individuals of these 53 species were indeed larger, more fecund, and more
      abundant in their introduced ranges. The overall mean, however, belied
      significant variability among species, as roughly half of the investigated
      species (N=27) performed similarly when compared to conspecific populations in
      their native range. Thus, although some invasive species are performing better in
      their new ranges, the pattern is not universal, and just as many are performing
      largely the same across ranges.

PMID- 23858640
TI  - Greater sexual reproduction contributes to differences in demography of invasive
      plants and their noninvasive relatives.
AB  - An understanding of the demographic processes contributing to invasions would
      improve our mechanistic understanding of the invasion process and improve the
      efficiency of prevention and control efforts. However, field comparisons of the
      demography of invasive and noninvasive species have not previously been
      conducted. We compared the in situ demography of 17 introduced plant species in
      St. Louis, Missouri, USA, to contrast the demographic patterns of invasive
      species with their less invasive relatives across a broad sample of angiosperms.
      Using herbarium records to estimate spread rates, we found higher maximum spread
      rates in the landscape for species classified a priori as invasive than for
      noninvasive introduced species, suggesting that expert classifications are an
      accurate reflection of invasion rate. Across 17 species, projected population
      growth was not significantly greater in invasive than in noninvasive introduced
      species. Among five taxonomic pairs of close relatives, however, four of the
      invasive species had higher projected population growth rates compared with their
      noninvasive relative. A Life Table Response Experiment suggested that the greater
      projected population growth rate of some invasive species relative to their
      noninvasive relatives was primarily a result of sexual reproduction. The greater
      sexual reproduction of invasive species is consistent with invaders having a life
      history strategy more reliant on fecundity than survival and is consistent with a
      large role of propagule pressure in invasion. Sexual reproduction is a key
      demographic correlate of invasiveness, suggesting that local processes
      influencing sexual reproduction, such as enemy escape, might be of general
      importance. However, the weak correlation of projected population growth with
      spread rates in the landscape suggests that regional processes, such as
      dispersal, may be equally important in determining invasion rate.

PMID- 23858641
TI  - Cytotype differences modulate eco-geographical differentiation in the widespread
      plant Centaurea stoebe.
AB  - The evolution of optimal life history strategies is central for the fitness of
      organisms in a given environment. Besides divergent selection, other factors may
      determine regional patterns of differentiation and contribute to life history
      evolution. In a common-garden environment over three years, we examined life
      history differentiation across different eco-geographical regions and effects of
      a specialist root-insect herbivore in the widespread European plant Centaurea
      stoebe, spotted knapweed. This plant occurs as two cytotypes with contrasting
      life cycles: monocarpic diploids and polycarpic tetraploids. In addition, the
      tetraploid cytotype has more recently become invasive in North America. We found
      significant regional differentiation in traits related to the timing of
      reproduction and reproductive allocation, but contrasting patterns in diploids
      and tetraploids. In diploids the degree of regional differentiation was higher
      compared to native tetraploids, and in the latter compared to invasive
      tetraploids. Furthermore, a pronounced shift in environmental conditions between
      the native and introduced range could have contributed to the differentiation
      between native and invasive tetraploids. The study also revealed the potential of
      the root-mining insect herbivore Agapeta zoegana, used as a biological control
      organism, to increase plant performance (presumably through overcompensatory
      growth), especially in the polycarpic tetraploids, and more so in the introduced
      populations. These findings suggest that patterns of regional differentiation in
      C. stoebe may be partly determined by divergent selection, but also strongly
      modulated by life cycle differences among geo-cytotypes. Furthermore, our study
      highlights the importance in applying a comprehensive and long-term approach when
      studying regional differentiation in plants.

PMID- 23858642
TI  - Does enemy loss cause release? A biogeographical comparison of parasitoid effects
      on an introduced insect.
AB  - The loss of natural enemies is a key feature of species introductions and is
      assumed to facilitate the increased success of species in new locales (enemy
      release hypothesis; ERH). The ERH is rarely tested experimentally, however, and
      is often assumed from observations of enemy loss. We provide a rigorous test of
      the link between enemy loss and enemy release by conducting observational surveys
      and an in situ parasitoid exclusion experiment in multiple locations in the
      native and introduced ranges of a gall-forming insect, Neuroterus saltatorius,
      which was introduced poleward, within North America. Observational surveys
      revealed that the gall-former experienced increased demographic success and lower
      parasitoid attack in the introduced range. Also, a different composition of
      parasitoids attacked the gall-former in the introduced range. These observational
      results show that enemies were lost and provide support for the ERH. Experimental
      results, however, revealed that, while some enemy release occurred, it was not
      the sole driver of demographic success. This was because background mortality in
      the absence of enemies was higher in the native range than in the introduced
      range, suggesting that factors other than parasitoids limit the species in its
      native range and contribute to its success in its introduced range. Our study
      demonstrates the importance of measuring the effect of enemies in the context of
      other community interactions in both ranges to understand what factors cause the
      increased demographic success of introduced species. This case also highlights
      that species can experience very different dynamics when introduced into
      ecologically similar communities.

PMID- 23858643
TI  - Genetic diversity within a dominant plant outweighs plant species diversity in
      structuring an arthropod community.
AB  - Plant biodiversity is being lost at a rapid rate. This has spurred much interest
      in elucidating the consequences of this loss for higher trophic levels.
      Experimental tests have shown that both plant species diversity and genetic
      diversity within a plant species can influence arthropod community structure.
      However, the majority of these studies have been conducted in separate systems,
      so their relative importance is currently unresolved. Furthermore, potential
      interactions between the two levels of diversity, which likely occur in natural
      systems, have not been investigated. To clarify these issues, we conducted three
      experiments in a freshwater sand dune ecosystem. We (1) independently manipulated
      plant species diversity, (2) independently manipulated genetic diversity within
      the dominant plant species, Ammophila breviligulata, and (3) jointly manipulated
      genetic diversity within the dominant plant and species diversity. We found that
      genetic diversity within the dominant plant species, Ammophila breviligulata,
      more strongly influenced arthropod communities than plant species diversity, but
      this effect was dependent on the presence of other species. In species mixtures,
      A. breviligulata genetic diversity altered overall arthropod community
      composition, and arthropod richness and abundance peaked at the highest level of
      genetic diversity. Positive nonadditive effects of diversity were detected,
      suggesting that arthropods respond to emergent properties of diverse plant
      communities. However, in the independent manipulations where A. breviligulata was
      alone, effects of genetic diversity were weaker, with only arthropod richness
      responding. In contrast, plant species diversity only influenced arthropods when
      A. breviligulata was absent, and then only influenced herbivore abundance. In
      addition to showing that genetic diversity within a dominant plant species can
      have large effects on arthropod community composition, these results suggest that
      understanding how species diversity and genetic diversity interact to influence
      community structure may be critically important for predicting the consequences
      of biodiversity loss.

PMID- 23858644
TI  - Gradient-based habitat affinities predict species vulnerability to drought.
AB  - Ecological fingerprints of climate change are becoming increasingly evident at
      broad geographical scales as measured by species range shifts and changes in
      phenology. However, finer-scale species-level responses to environmental
      fluctuations may also provide an important bellwether of impending future
      community responses. Here we examined changes in abundance of butterfly species
      along a hydrological gradient of six montane meadow habitat types in response to
      drought. Our data collection began prior to the drought, and we were able to
      track changes for 11 years, of which eight were considered mild to extreme
      drought conditions. We separated the species into those that had an affinity for
      hydric vs. xeric habitats. We suspected that drought would favor species with
      xeric habitat affinities, but that there could be variations in species-level
      responses along the hydrological gradient. We also suspected that mesic meadows
      would be most sensitive to drought conditions. Temporal trajectories were modeled
      for both species groups (hydric vs. xeric affinity) and individual species.
      Abundances of species with affinity for xeric habitats increased in virtually all
      meadow types. Conversely, abundances of species with affinity for hydric habitats
      decreased, particularly in mesic and xeric meadows. Mesic meadows showed the most
      striking temporal abundance trajectory: Increasing abundances of species with
      xeric habitat affinity were offset by decreasing or stable abundances of species
      with hydric habitat affinity. The one counterintuitive finding was that, in some
      hydric meadows, species with affinity for hydric habitats increased. In these
      cases, we suspect that decreasing moisture conditions in hydric meadows actually
      increased habitat suitability because sites near the limit of moisture extremes
      for some species became more acceptable. Thus, species responses were relatively
      predictable based upon habitat affinity and habitat location along the
      hydrological gradient, and mesic meadows showed the highest potential for changes
      in community composition. The implications of these results are that longer-term
      changes due to drought could simplify community composition, resulting in
      prevalence of species tolerant to drying conditions and a loss of species
      associated with wetter conditions. We contend that this application of gradient
      analysis could be valuable in assessing species vulnerability of other taxa and
      ecosystems.

PMID- 23858645
TI  - Ontogenetic functional diversity: size structure of a keystone predator drives
      functioning of a complex ecosystem.
AB  - A central challenge in community ecology is to understand the connection between
      biodiversity and the functioning of ecosystems. While traditional approaches have
      largely focused on species-level diversity, increasing evidence indicates that
      there exists substantial ecological diversity among individuals within species.
      By far, the largest source of this intraspecific diversity stems from variation
      among individuals in ontogenetic stage and size. Although such ontogenetic shifts
      are ubiquitous in natural communities, whether and how they scale up to influence
      the structure and functioning of complex ecosystems is largely unknown. Here we
      take an experimental approach to examine the consequences of ontogenetic niche
      shifts for the structure of communities and ecosystem processes. In particular we
      experimentally manipulated the stage structure in a keystone predator, larvae of
      the dragonfly Anax junius, in complex experimental pond communities to test
      whether changes in the population stage or size structure of a keystone species
      scale up to alter community structure and ecosystem processes, and how functional
      differences scale with relative differences in size among stages. We found that
      the functional role of A. junius was stage-specific. Altering what stages were
      present in a pond led to concurrent changes in community structure, primary
      producer biomass (periphyton and phytoplankton), and ultimately altered ecosystem
      processes (respiration and net primary productivity), indicating a strong, but
      stage-specific, trophic cascade. Interestingly, the stage-specific effects did
      not simply scale with size or biomass of the predator, but instead indicated
      clear ontogenetic niche shifts in ecological interactions. Thus, functional
      differences among stages within a keystone species scaled up to alter the
      functioning of entire ecosystems. Therefore, our results indicate that the
      classical approach of assuming an average functional role of a species can be
      misleading because functional roles are dynamic and will change with shifts in
      the stage structure of the species. In general this emphasizes the importance of
      accounting for functional diversity below the species level to predict how
      natural and anthropogenic changes alter the functioning of natural ecosystems.

PMID- 23858646
TI  - Predator density and timing of arrival affect reef fish community assembly.
AB  - Most empirical studies of predation use simple experimental approaches to
      quantify the effects of predators on prey (e.g., using constant densities of
      predators, such as ambient vs. zero). However, predator densities vary in time,
      and these effects may not be well represented by studies that use constant
      predator densities. Although studies have independently examined the importance
      of predator density, temporal variability, and timing of arrival (i.e., early or
      late relative to prey), the relative contribution of these different predator
      regimes on prey abundance, diversity, and composition remains poorly understood.
      The hawkfish (Paracirrhites arcatus), a carnivorous coral reef fish, exhibits
      substantial variability in patch occupancy, density, and timing of arrival to
      natural reefs. Our field experiments demonstrated that effects of hawkfish on
      prey abundance depended on both hawkfish density and the timing of their arrival,
      but not on variability in hawkfish density. Relative to treatments without
      hawkfish, hawkfish presence reduced prey abundance by 50%. This effect increased
      with a doubling of hawkfish density (an additional 33% reduction), and when
      hawkfish arrived later during community development (a 34% reduction). Hawkfish
      did not affect within-patch diversity (species richness), but they increased
      between-patch diversity (beta) based on species incidence (22%), and caused
      shifts in species composition. Our results suggest that the timing of predator
      arrival can be as important as predator density in modifying prey abundance and
      community composition.

PMID- 23858647
TI  - Two's company, three's a crowd: food and shelter limitation outweigh the benefits
      of group living in a shoaling fish.
AB  - Identifying how density and number-dependent processes regulate populations is
      important for predicting population response to environmental change. Species
      that live in groups, such as shoaling fish, can experience both direct density
      dependent mortality through resource limitation and inverse number-dependent
      mortality via increased feeding rates and predator evasion in larger groups. To
      investigate the role of these processes in a temperate reef fish population, we
      manipulated the density and group size of the shoaling species Trachinops
      caudimaculatus on artificial patch reefs at two locations with different predator
      fields in Port Phillip Bay, Australia. We compared mortality over four weeks to
      estimates of predator abundance and per capita availability of refuge and food to
      identify mechanisms for density or number dependence. Mortality was strongly
      directly density dependent throughout the experiment, regardless of the dominant
      predator group; however, the limiting resource driving this effect changed over
      time. In the first two weeks when densities were highest, density-dependent
      mortality was best explained by refuge competition and the abundance of benthic
      predators. During the second two weeks, food competition best explained the
      pattern of mortality. We detected no effect of group size at either location,
      even where pelagic-predator abundance was high. Overall, direct density effects
      were much stronger than those of group size, suggesting little survival advantage
      to shoaling on isolated patch reefs where resource competition is high. This
      study is the first to observe a temporal shift in density-dependent mechanisms in
      reef fish, and the first to observe food limitation on short temporal scales.
      Food competition may therefore be an important regulator of postsettlement reef
      fish cohorts after the initial intense effects of refuge limitation and
      predation.

PMID- 23858648
TI  - Historical thermal regimes define limits to coral acclimatization.
AB  - Knowledge of the degree to which corals undergo physiological acclimatization or
      genetic adaptation in response to changes in their thermal environment is crucial
      to the success of coral reef conservation strategies. The potential of corals to
      acclimatize to temperatures exceeding historical thermal regimes was investigated
      by reciprocal transplantation of Acropora millepora colonies between the warm
      central and cool southern regions of the Great Barrier Reef (GBR) for a duration
      of 14 months. Colony fragments retained at native sites remained healthy, whereas
      transplanted fragments, although healthy over initial months when temperatures
      remained within native thermal regimes, subsequently bleached and suffered
      mortality during seasonal temperature extremes. Corals hosting Symbiodinium D
      transplanted to the southern GBR bleached in winter and the majority suffered
      whole (40%; n=20 colonies) or partial (50%) mortality at temperatures 1.1 degrees
      C below their 15-year native minimum. In contrast, corals hosting Symbiodinium C2
      transplanted to the central GBR bleached in summer and suffered whole (50%; n=10
      colonies) or partial (42%) mortality at temperatures 2.5 degrees C above their 15
      year native maximum. During summer bleaching, the dominant Symbiodinium type
      changed from C2 to D within corals transplanted to the central GBR. Corals
      transplanted to the cooler, southern GBR grew 74-80% slower than corals at their
      native site, and only 50% of surviving colonies reproduced, at least partially
      because of cold water bleaching of transplants. Despite the absence of any visual
      signs of stress, corals transplanted to the warmer, central GBR grew 52-59% more
      slowly than corals at their native site before the summer bleaching (i.e., from
      autumn to spring). Allocation of energy to initial acclimatization or
      reproduction may explain this pattern, as the majority (65%) of transplants
      reproduced one month earlier than portions of the same colonies retained at the
      southern native site. All parameters investigated (bleaching, mortality,
      Symbiodinium type fidelity, reproductive timing) demonstrated strong interactions
      between genotype and environment, indicating that the acclimatization potential
      of A. millepora populations may be limited by adaptation of the holobiont to
      native thermal regimes.

PMID- 23858649
TI  - Additive effects of physical stress and herbivores on intertidal seaweed
      biodiversity.
AB  - Patterns in rocky intertidal seaweed biodiversity influence the resilience and
      functioning of these important primary producer communities. In turn, seaweed
      biodiversity patterns are the result of many ecological factors. We determined
      the influences of thermal and desiccation stress, herbivory, and nutrients on
      seaweed biodiversity on a northern California rocky shoreline. In a fully crossed
      design at two tidal heights at wave-protected and exposed sites, we deployed
      screens to reduce stress, removed herbivores, and added nutrients for 18 months.
      The treatments reduced temperature, increased relative humidity, decreased
      herbivore abundances, and increased nitrogen in both seawater and seaweeds.
      Seaweed abundance and biodiversity (cover, biomass, species richness, diversity,
      evenness, and community composition) were influenced by tidal height, physical
      stress, and herbivores. Wave exposure affected all response variables except
      biomass and evenness. Stress and herbivores had independent additive effects on
      seaweed abundance and diversity. Physical stress did not make the community as a
      whole more susceptible to herbivores, and screens had overarching positive
      effects on seaweed biodiversity even though they also had positive effects on
      herbivore abundance. Nutrients had virtually no effect on seaweed biodiversity,
      and we observed no bottom-up effects of nutrient addition on herbivore density or
      biomass. Small green algae and diatoms were important contributors to overall
      algal cover and to changes in composition across treatments, but larger
      macroalgae dominated the species richness response. The striking absence of
      interactions between stress and herbivory highlights how seaweed communities can
      respond independently to important drivers of biodiversity. Thus, nonadditive,
      potentially synergistic effects do not necessarily complicate the understanding
      of how seaweed biodiversity responds to environmental change.

PMID- 23858650
TI  - Reddened seascapes: experimentally induced shifts in 1/f spectra of spatial
      variability in rocky intertidal assemblages.
AB  - Ecological tests of 1/f-noise models have advanced our understanding of how
      environmental fluctuations affect population abundance and species distributions.
      Most empirical studies have been conducted under controlled laboratory conditions
      and have focused on individual drivers. We present the results of a four-year
      field experiment in which canopy presence/absence and the availability of primary
      space were manipulated as red-noise and white-noise spatial processes,
      respectively, to evaluate their separate and compounded effects on algal turf
      distribution in a rocky intertidal community. Algal turfs closely tracked spatial
      variation in canopy distribution, displaying a reddened spectrum of spatial
      variation. Surprisingly, white-noise clearings also induced a red-shift in turf
      distribution, a pattern that was related to a nonlinear relation between gap size
      and turf colonization. The two disturbances interacted antagonistically,
      dampening the red-shift of turf distribution. Our results provide evidence of
      experimentally induced shifts in the spectrum of a spatial variable under natural
      environmental conditions.

PMID- 23858651
TI  - Mammal predator and prey species richness are strongly linked at macroscales.
AB  - Predator-prey interactions play an important role for species composition and
      community dynamics at local scales, but their importance in shaping large-scale
      gradients of species richness remains unexplored. Here, we use global range maps,
      structural equation models (SEM), and comprehensive databases of dietary
      preferences and body masses of all terrestrial, non-volant mammals worldwide, to
      test whether (1) prey bottom-up or predator top-down relationships are important
      drivers of broad-scale species richness gradients once the environment and human
      influence have been accounted for, (2) predator-prey richness associations vary
      among biogeographic regions, and (3) body size influences large-scale covariation
      between predators and prey. SEMs including only productivity, climate, and human
      factors explained a high proportion of variance in prey richness (R2=0.56) but
      considerably less in predator richness (R2=0.13). Adding predator-to-prey or prey
      to-predator paths strongly increased the explained variance in both cases (prey
      R2=0.79, predator R2=0.57), suggesting that predator-prey interactions play an
      important role in driving global diversity gradients. Prey bottom-up effects
      prevailed over productivity, climate, and human influence to explain predator
      richness, whereas productivity and climate were more important than predator top
      down effects for explaining prey richness, although predator top-down effects
      were still significant. Global predator-prey associations were not reproduced in
      all regions, indicating that distinct paleoclimate and evolutionary histories
      (Africa and Australia) may alter species interactions across trophic levels.
      Stronger cross-trophic-level associations were recorded within categories of
      similar body size (e.g., large prey to large predators) than between them (e.g.,
      large prey to small predators), suggesting that mass-related energetic and
      physiological constraints influence broad-scale richness links, especially for
      large-bodied mammals. Overall, our results support the idea that trophic
      interactions can be important drivers of large-scale species richness gradients
      in combination with environmental effects.

PMID- 23858652
TI  - Asynchronous food-web pathways could buffer the response of Serengeti predators
      to El Nino Southern Oscillation.
AB  - Understanding how entire ecosystems maintain stability in the face of climatic
      and human disturbance is one of the most fundamental challenges in ecology.
      Theory suggests that a crucial factor determining the degree of ecosystem
      stability is simply the degree of synchrony with which different species in
      ecological food webs respond to environmental stochasticity. Ecosystems in which
      all food-web pathways are affected similarly by external disturbance should
      amplify variability in top carnivore abundance over time due to population
      interactions, whereas ecosystems in which a large fraction of pathways are
      nonresponsive or even inversely responsive to external disturbance will have more
      constant levels of abundance at upper trophic levels. To test the mechanism
      underlying this hypothesis, we used over half a century of demographic data for
      multiple species in the Serengeti (Tanzania) ecosystem to measure the degree of
      synchrony to variation imposed by an external environmental driver, the El Nino
      Southern Oscillation (ENSO). ENSO effects were mediated largely via changes in
      dry-season vs. wet-season rainfall and consequent changes in vegetation
      availability, propagating via bottom-up effects to higher levels of the Serengeti
      food web to influence herbivores, predators and parasites. Some species in the
      Serengeti food web responded to the influence of ENSO in opposite ways, whereas
      other species were insensitive to variation in ENSO. Although far from
      conclusive, our results suggest that a diffuse mixture of herbivore responses
      could help buffer top carnivores, such as Serengeti lions, from variability in
      climate. Future global climate changes that favor some pathways over others,
      however, could alter the effectiveness of such processes in the future.

PMID- 23858653
TI  - Climatic variation and age-specific survival in Asian elephants from Myanmar.
AB  - Concern about climate change has intensified interest in understanding how
      climatic variability affects animal life histories. Despite such effects being
      potentially most dramatic in large, long-lived, and slowly reproducing
      terrestrial mammals, little is known of the effects of climatic variation on
      survival in those species. Asian elephants (Elephas maximus) are endangered
      across their distribution, and inhabit regions characterized by high seasonality
      of temperature and rainfall. We investigated the effects of monthly climatic
      variation on survival and causes of death in Asian elephants using a unique
      demographic data set of 1024 semi-captive, longitudinally monitored elephants
      from four sites in Myanmar between 1965 and 2000. Temperature had a significant
      effect on survival in both sexes and across all ages. For elephants between 1
      month and 17 years of age, maximal survival was reached at -24 degrees C, and any
      departures from this temperature increased mortality, whereas neonates and mature
      elephants had maximal survival at even lower temperatures. Although males
      experienced higher mortality overall, sex differences in these optimal
      temperatures were small. Because the elephants spent more time during a year in
      temperatures above 24 degrees C than in temperatures below it, most deaths
      occurred at hot (temperatures>24 degrees C) rather than cold periods. Decreased
      survival at higher temperatures resulted partially from increased deaths from
      infectious disease and heat stroke, whereas the lower survival in the coldest
      months was associated with an increase in noninfectious diseases and poor health
      in general. Survival was also related to rainfall, with the highest survival
      rates during the wettest months for all ages and sexes. Our results show that
      even the normal-range monsoon variation in climate can exert a large impact on
      elephant survival in Myanmar, leading to extensive absolute differences in
      mortality; switching from favorable to unfavorable climatic conditions within
      average years doubled the odds for mortality. The persistence of a long-term
      trend toward higher global temperatures, combined with the possibility of higher
      variation in temperature between seasons, may pose a challenge to the survival of
      species such as Asian elephants.

PMID- 23858654
TI  - Adaptive thermoregulation during summer in two populations of an arid-zone
      passerine.
AB  - Heterothermy plays an important role in lowering the costs of thermoregulation in
      endotherms by reducing water and energy requirements. We tested predictions that
      birds in arid habitats should express fine-scale variation in their
      thermoregulatory patterns as a function of prevailing climatic conditions. We
      assessed effects of air temperature (Tair) and water vapor pressure deficit (D)
      on body temperature (Tb) in free-living White-browed Sparrow-Weavers (Plocepasser
      mahali) during summer in two arid habitats in the Kalahari Desert, South Africa,
      using data from a dry period at a hot, desert site (n=7 birds), and during a dry
      period (n=4 birds) and a wet period (n=5 birds) at a milder, semi-desert site.
      The desert birds maintained a significantly higher set-point Tb (41.5 degrees+/
      0.2 degrees C, mean-SD) than semi-desert birds (40.2 degrees+/-0.2 degrees C).
      During the warmest part of day (12:00-18:00 hours), Tb increased significantly
      during periods of high Tair and/or high humidity, and mean and maximum Tb were up
      to 1.40 and 2.3 degrees C, respectively, above normal levels. However, as Tair
      increased, birds at the desert site maintained Tb at or below set-point levels
      for a greater proportion of the time than birds at the semi-desert site. Birds at
      the desert site also expressed a greater magnitude of daily heterothermy
      (heterothermy index, HI=2.4 degrees+/-0.3 degrees C, mean+/-SD) than birds at the
      semi-desert site: the latter population showed a greater magnitude of
      heterothermy during a dry period (HI=2.1 degrees+/-0.3 degrees C) than during a
      wet period (HI=1.6 degrees+/-0.2 degrees C). Birds continued foraging throughout
      the warmest part of the day, despite the fact that heat dissipation (percentage
      of time spent panting and wing-spreading) increased significantly with increasing
      Tair. Our findings reveal that populations can vary in their thermoregulatory
      responses in both space and time and suggest that small changes in Tair can have
      significant effects on thermoregulation in free-ranging desert birds, even when
      Tair<Tb. These data have important implications for assessing vulnerability of
      species to climate change, suggesting that sensitivity should be assessed at the
      population, rather than species, level.

PMID- 23858655
TI  - Influence of competition and rainfall manipulation on the growth responses of
      savanna trees and grasses.
AB  - In this study, we explored how rainfall manipulation influenced competitive
      interactions between grasses and juvenile trees (small nonreproductive trees
      capable of resprouting) in savanna. To do this, we manipulated rainfall amount in
      the field using an incomplete factorial experiment that determined the effects of
      rainfall reduction, no manipulation, rainfall addition, and competition between
      grasses and trees on grass and tree growth. As response variables, we focused on
      several measures of tree growth and Disc Pasture Meter settling height as an
      estimate of grass aboveground biomass. We conducted the study over four years, at
      two sites in the Kruger National Park, South Africa. Our results show that
      rainfall manipulation did not have substantial effects on any of the measures of
      tree growth we considered. However, trees at plots where grasses had been removed
      grew on average 15 cm more in height and 1.3-1.7 times more in basal area per
      year than those in plots with grasses. Grass biomass was not influenced by the
      presence of trees but was significantly and positively influenced by rainfall
      addition. These findings were not fundamentally influenced by soil type or by
      prevailing precipitation, suggesting applicability of our results to a wide range
      of savannas. Our results suggest that, in savannas, increasing rainfall serves to
      increase the competitive pressure exerted by grasses on trees. The implication is
      that recruitment into the adult tree stage from the juvenile stage is most likely
      in drought years when there is little competition from grass for resources and
      grass fuel loads are low.

PMID- 23858656
TI  - Thirty-two years of change in an old-growth Ohio beech-maple forest.
AB  - Old-growth forests dominated by understory-tolerant tree species are among forest
      types most likely to be in equilibrium. However, documentation of the degree to
      which they are in equilibrium over decades-long time periods is lacking. Changes
      in climate, pathogens, and land use all are likely to impact stand
      characteristics and species composition, even in these forests. Here, 32 years of
      vegetation changes in an old-growth beech (Fagus grandifolia)-sugar maple (Acer
      saccharum) forest in Hueston Woods, southwest Ohio, USA, are summarized. These
      changes involve canopy composition and structure, turnover in snags, and
      development of vegetation in treefall gaps. Stand basal area and canopy density
      have changed little in 32 years. However, beech has decreased in canopy
      importance (49% to 32%) while sugar maple has increased (32% to 47%). Annual
      mortality was about 1.3% throughout the study period. Mortality rates increased
      with stem size, but the fraction of larger stems increased due to ingrowth from
      smaller size classes. Beech was represented by more very large stems than small
      canopy stems: over time, death of those larger stems with inadequate replacement
      has caused the decrease in beech importance. Sugar maple was represented by more
      small canopy stems whose growth has increased its importance. The changes in
      beech and sugar maple relative importance are hypothesized to be due to forest
      fragmentation mostly from the early 1800s with some possible additional effects
      associated with the formation of the state park. Snag densities (12-16 snags/ha)
      and formation rates (1-3 snags.ha(-1).yr(-1)) remained consistent. The treefall
      gaps previously studied are closing, with a few, large stems remaining. Death of
      gap border trees occurs consistently enough to favor species able to combine
      growth in gaps and survival in the understory.

PMID- 23858657
TI  - A directed network analysis of heterospecific pollen transfer in a biodiverse
      community.
AB  - Community studies have shown that plant species are often pollinated by multiple
      pollinators; however, networks of heterospecific pollen transfer (HPT) in natural
      communities remain largely unexplored. We analyzed pollen deposition on stigmas
      of 57 flowering species to build a picture of plant-plant interactions via HPT in
      a biodiverse alpine meadow in southwest China. Plant species were categorized as
      pollen donors or recipients by their link numbers and link qualities. We
      identified 3609 heterospecific pollen grains, representing 410 links among 69
      pollen species. Each plant species received on average 7.2 pollen species and
      donated its pollen to 5.5 species; only a few species donated or received large
      amounts of pollen or pollen from a large number of species. Compared to
      specialized plants, generalized plants tended to receive more heterospecific
      pollen but exported no more pollen to other species. Plant position in the
      network was related to both floral traits (stigma position) and pollinator
      generalization level. When different species share the same pollinator,
      bidirectional HPT may occur, but this was rarely observed in the species-rich
      community, indicating that interspecific pollen interference was largely
      unidirectional. Our study highlights the importance of understanding how
      sympatric flowering plants reduce deleterious effects of HPT, for example via
      stigma position. This study is the first to present a pollen transfer network for
      an entire community and to unravel its properties using directed network
      analysis.

PMID- 23858658
TI  - Does exogenous carbon extend the realized niche of canopy lichens? Evidence from
      sub-boreal forests in British Columbia.
AB  - Foliose lichens with cyanobacterial bionts (bipartite and tripartite) form a
      distinct assemblage of epiphytes strongly associated with humid microclimatic
      conditions in inland British Columbia. Previous research showed that these cyano-
      and cephalolichen communities are disproportionately abundant and species-rich on
      conifer saplings beneath Populus compared to beneath other tree species. More
      revealing, lichens with cyanobacterial bionts were observed beneath Populus even
      in stands that did not otherwise support them. We experimentally test the
      hypothesis that this association is due to the interception of glucose-rich
      nectar that is exuded from Populus extra-floral nectaries (EFN). Using CO2 flux
      measurements and phospholipid fatty acid (PLFA) analysis with experimental
      applications of 13C6-labeled glucose, we demonstrate that cyano- and
      cephalolichens have a strong respiratory response to glucose. Lichens treated
      with glucose had lower net photosynthesis and higher establishment rates than
      control thalli. Furthermore, lichens with cyanobacterial bionts rapidly
      incorporate exogenous 13C into lichen fatty acid tissues. A large proportion of
      the 13C taken up by the lichens was incorporated into fungal biomarkers,
      suggesting that the mycobiont absorbed and assimilated the majority of applied
      13C6 glucose. Our observations suggest that both cyanolichens and cephalolichens
      may utilize an exogenous source of glucose, made available by poplar EFNs. The
      exogenous C may enable these lichens to become established by providing a source
      of C for fungal respiration despite drought-induced inactivity of the
      cyanobacterial partner. As such, the mycobiont may adopt an alternative
      nutritional strategy, using available exogenous carbon to extend its realized
      niche.

PMID- 23858659
TI  - A semiparametric Bayesian method for detecting Allee effects.
AB  - The importance of Allee effects has long been recognized both in theoretical
      studies of population dynamics and in conservation sciences. Although the
      necessary conditions for Allee effects to occur (e.g., difficulty in finding
      mates and mortality driven by generalist predators at low density) would seem to
      apply to many species, evidence for Allee effects in natural populations is
      equivocal at best. This apparent scarcity might be an artifact driven by poor
      power to detect them with traditional parametric models. To circumvent this
      potential problem, we developed a semiparametric Bayesian method based on a
      Gaussian process prior. We validated the method using simulated data sets and
      applied it to three herring data sets.

PMID- 23858660
TI  - "It's all about giving back" - a toast to the board!

PMID- 23858661
TI  - Impact of internet posting of restaurant inspection scores on critical
      violations.
AB  - Posting restaurant inspection scores on the Internet as a tool for improving food
      safety is becoming more common. The purpose of the study described in this
      article was to evaluate the association between Internet posting of restaurant
      inspection scores and the five most frequently cited critical violations in Salt
      Lake County, Utah. The study examined 2,995 inspections conducted at 796 full
      service and fast food restaurants for a one-year period before and after launch
      of a restaurant inspection Web site. Critical violations decreased significantly
      after the Web site launch compared to before-launch levels. The greatest
      improvements were found in temperature holding violations (odds ratio = 0.75, p <
      .001), hygiene practices violations (odds ratio = 0.68, p < .001) and equipment
      cleanliness violations (odds ratio = 0.58, p < .001). Restaurant type (full
      service, fast food), inspector experience, and season were significantly
      associated with the decrease in violations.

PMID- 23858662
TI  - A health and environmental profile of the dry cleaning industry in King County,
      Washington.
AB  - Workers in the dry cleaning industry are exposed to a variety of harmful
      solvents, and poor work practices can result in extensive environmental
      contamination. Of particular concern is perchloroethylene (PERC), which is the
      most commonly used cleaning solvent. This chlorinated hydrocarbon is a pervasive
      environmental contaminant and a probable human carcinogen. PERC is also a
      neurotoxin and is toxic to the liver and kidneys. The study described here was
      comprised of key informant interviews, site visits, and a countywide business
      survey. The 64% response rate to the survey suggests that the results are likely
      representative of King County's dry cleaning industry. Dry cleaning was
      determined to be dominated by small, Korean-owned, family-run businesses.
      Although the use of PERC as the primary dry cleaning agent has decreased in
      recent years, this solvent is still used by the majority of businesses. This
      industry would benefit from regulatory intervention in concert with an
      educational campaign and enhanced technical and financial assistance. For any
      intervention to be effective, however, it must account for the unique financial
      and demographic characteristics of this industry.

PMID- 23858664
TI  - The exploration of effects of Chinese cultural values on the attitudes and
      behaviors of Chinese restaurateurs toward food safety training.
AB  - Foodborne illness is a challenge in the production and service of ethnic foods.
      The purpose of the study described in this article was to explore variables
      influencing the behaviors of U.S. Chinese restaurant owners/operators regarding
      the provision of food safety training in their restaurants. Seventeen major
      Chinese cultural values were identified through individual interviews with 20
      Chinese restaurant owners/operators. Most participants felt satisfied with their
      previous health inspections. Several expressed having difficulty, however,
      following the health inspectors' instructions and in understanding the health
      inspection report. A few participants provided food safety training to their
      employees due to state law. Lack of money, time, labor/energy, and a perceived
      need for food safety training were recognized as major challenges to providing
      food safety training in Chinese restaurants. Videos, case studies, and food
      safety training handbooks were the most preferred food safety training methods of
      Chinese restaurant owners/operators, and Chinese was the preferred language in
      which to conduct the training.

PMID- 23858663
TI  - Public infrastructure disparities and the microbiological and chemical safety of
      drinking and surface water supplies in a community bordering a landfill.
AB  - The historically African-American Rogers-Eubanks community straddles
      unincorporated boundaries of two municipalities in Orange County, North Carolina,
      and predates a regional landfill sited along its border in 1972. Community
      members from the Rogers-Eubanks Neighborhood Association (RENA), concerned about
      deterioration of private wells and septic systems and a lack of public drinking
      water and sewer services, implemented a community-driven research partnership
      with university scientists and community-based organizations to investigate water
      and sewer infrastructure disparities and the safety of drinking and surface water
      supplies. RENA drafted memoranda of agreement with partners and trained community
      monitors to collect data (inventory households, map water and sewer
      infrastructure, administer household water and sewer infrastructure surveys, and
      collect drinking and surface water samples). Respondents to the surveys reported
      pervasive signs of well vulnerability (100%) and septic system failure (68%).
      Each 100-m increase in distance from the landfill was associated with a 600 most
      probable number/100 mL decrease in enterococci concentrations in surface water
      (95% confidence interval = -1106, -93). Pervasive private household water and
      sewer infrastructure failures and poor water quality were identified in this
      community bordering a regional landfill, providing evidence of a need for
      improved water and sanitation services.

PMID- 23858666
TI  - Environmental Public Health Online Course (EPHOC) series: Are we making a
      difference?

PMID- 23858665
TI  - Integrating research and community organizing to address water and sanitation
      concerns in a community bordering a landfill.

PMID- 23858667
TI  - Moving from just-in-case to just-in-time living.

PMID- 23858668
TI  - Why your jobs are important.

PMID- 23858669
TI  - Dues !#$%&*!!

PMID- 23858670
TI  - A good time to retire is....

PMID- 23858671
TI  - How to build up the perfect tooth.

PMID- 23858672
TI  - A calculated investment in technology.

PMID- 23858673
TI  - Is dentistry going to get into the salivary diagnostics game or watch from the
      sidelines?
AB  - What is salivary diagnostics and why should you care? Most of us dentists try to
      avoid or control saliva as it interferes with access, or chemical interactions in
      dental materials or impression materials, or when it is simply a nuisance.
      Periodically, we may note reduced flow or encounter a patient with xerostomia.
      Correspondingly, we then manage the many of today's existing commercialized oral
      based tests were yesterday's proposed ideas or concepts, captured in the 1993 New
      York Academy of Sciences Conference on oral based diagnostics. When coupled with
      the emerging point-of-care technology, the potential of salivary diagnostics is
      even more compelling. In this section, I hope to elucidate for the reader the
      potential of salivary diagnostics for the dental profession and So what is the
      value proposition? How could this disruptive technology serve the dentist and the
      patients they treat? What must occur to facilitate the ongoing development and
      introduction of salivary diagnostics into the marketplace?

PMID- 23858674
TI  - Diagnostic discussion. Odontogenic myxoma.

PMID- 23858675
TI  - Resisting technology change.

PMID- 23858676
TI  - Defined contribution health care strategy--is it right for your small group?

PMID- 23858677
TI  - Transparency and communication: keys to a strong dentist/technician relationship.

PMID- 23858678
TI  - Impact of the Affordable Care Act on dentistry.

PMID- 23858679
TI  - Dental managed care.

PMID- 23858680
TI  - The three R's: reorganizing, relocating, restructuring.

PMID- 23858681
TI  - A smoke-free Texas? Yes, please.

PMID- 23858682
TI  - What's next.

PMID- 23858683
TI  - Survey says...renewed commitment to safety needed.

PMID- 23858684
TI  - NHCA conference highlights top hearing conservation trends.

PMID- 23858685
TI  - Effective safety recognition programs: the do's and don'ts.

PMID- 23858686
TI  - Tangible incentive programs improve safety results.

PMID- 23858687
TI  - Building a culture of safety.

PMID- 23858688
TI  - Keys to boosting CPR quality.

PMID- 23858689
TI  - Respiratory 101.

PMID- 23858690
TI  - Applying personal protective grounds.

PMID- 23858691
TI  - Preventing fires in fume extraction systems.

PMID- 23858692
TI  - Helicopter EMS under scrutiny again.

PMID- 23858693
TI  - Evolving with times.

PMID- 23858694
TI  - Role of the dental assisant in addressing access to care.

PMID- 23858695
TI  - Triple tray crown and bridge procedures: a guide to how dental assistants can
      assist the dentist: part 1.
AB  - The manual dual-arch (or triple tray) technique is an efficient way of making a
      definitive impression and making temporary provisional restorations for crown and
      bridge procedures. This article demonstrates how a dental assistant can assist a
      dentist during triple tray crown and bridge procedures. This is the first part of
      a two-part article, and explains mixing impression materials, making pre
      operative dual-arch impressions, deciding in what situations to use separate arch
      impressions instead of the triple tray, and introduces the topic of making
      provisional restorations. In the future, in-office CAD-CAM scanning and milling
      of restorations, or digital scanning of tooth preparations, followed by e-mailing
      the scans to a dental laboratory, may reduce the frequency of use of the manual
      triple tray impression technique. However, its intrinsic efficiency may prevent
      it from becoming obsolete.

PMID- 23858696
TI  - Salute to chairside executives.

PMID- 23858697
TI  - Employee engagement: a workplace issue for dental assistants.

PMID- 23858698
TI  - Halitosis: you take my breath away.

PMID- 23858699
TI  - A little learning is a dang'rous thing.

PMID- 23858700
TI  - Using the dynamic indicators of basic early literacy skills with students who are
      deaf or hard of hearing: perspectives of a panel of experts.
AB  - Early literacy skills serve as the foundation for the development of subsequent
      reading skills and strategies. Increasingly, educators are administering early
      literacy assessments to identify young students who are at risk for reading
      failure and providing them with additional evidence based interventions. The most
      widely used assessments for reading in preschools and elementary schools for
      typical hearing students are the Dynamic Indicators of Basic Early Literacy
      Skills (DIBELS). The purpose of this study was to gather the perceptions of a
      panel of experts in the area of reading and individuals who are deaf or hard of
      hearing regarding the potential appropriateness of using the subtests of the
      DIBELS with students who are deaf or hard of hearing. Results, as well as
      practical and research implications, are provided.

PMID- 23858701
TI  - Phonology matters: a comprehensive investigation of reading and spelling skills
      of school-age children with mild to moderate sensorineural hearing loss.
AB  - The investigators measured 7 literacy skills in a group of 21 school-age children
      with mild to moderate sensorineural hearing loss (MSNH group), and compared the
      scores to those of 2 age-matched groups: children with dyslexia (DYS group) and,
      as a control, typically developing hearing children (CA group). The MSNH group
      performed consistently below the CA group but better than the DYS group, an
      indication that differences in the groups' phonological processing profiles might
      be an important discriminating feature. Interestingly, the MSNH group showed a
      selective impairment in word reading accuracy only, whereas their reading rate
      was relatively unaffected. Children with MSNH who show weak phonological
      awareness skills seem to compensate by relying on orthographic recognition
      associated with rapid naming ability. To determine which children with MSNH are
      at high risk for depressed reading achievement, testing across a widerange of
      literacy skills should be considered.

PMID- 23858702
TI  - The effect of education on the occupational status of deaf and hard of hearing 26
      to-64-year-olds.
AB  - In the last quarter of the 20th century, federal legislation sought to eliminate
      disability-based discrimination by requiring reasonable accommodations in school
      and the workplace. One result of this legislation has been increased access to
      U.S. colleges and universities by deaf and hard of hearing persons. The present
      article reviews the literature on employment of persons who are deaf or hard of
      hearing and reports results of a recent analysis that used the 2010 American
      Community Survey (U.S. Census Bureau, 2010a). It was found that significant gains
      in college attendance and graduation occurred during the period, with individuals
      who attained a college degree realizing increased employment and earnings
      relative to individuals who had not graduated. It was also found that college
      graduation helps reduce the gap between the earnings of deaf persons with a
      college degree and those of comparably educated hearing persons.

PMID- 23858703
TI  - Itinerant deaf educator and general educator perceptions of the D/HH push-in
      model.
AB  - A qualitative case study using the deaf and hard of hearing (D/HH) push-in model
      was conducted on the perceptions of 3 itinerant deaf educators and 3 general
      educators working in 1 school district. Participants worked in pairs of 1 deaf
      educator and 1 general educator at 3 elementary schools. Open-ended research
      questions guided the study, which was concerned with teachers' perceptions of the
      model in general and with the model's advantages, disadvantages, and
      effectiveness. Data collected from observations, one-to-one interviews, and a
      focus group interview enabled the investigator to uncover 4 themes: Participants
      (a) had an overall positive experience, (b) viewed general education immersion as
      an advantage, (c) considered high noise levels a disadvantage, and (d) believed
      the effectiveness of the push-in model was dependent on several factors, in
      particular, the needs of the student and the nature of the general education
      classroom environment.

PMID- 23858704
TI  - Teachers' perceptions of the inclusion of children with hearing loss in general
      education settings.
AB  - A questionnaire was used to document the attitudes of 63 classroom teachers in
      Ottawa, Canada, toward inclusive education for students with hearing loss. The
      objective was to determine whether teachers had the attitudes, knowledge, and
      teaching skills proposed to underlie the effective inclusion of these students in
      regular classrooms. It was found that the teachers had favorable attitudes toward
      inclusion for students with hearing loss, felt confident in their ability to
      teach them, and were knowledgeable about the effects of hearing loss on language
      and learning. They also clearly indicated that their teacher education programs
      had insufficiently prepared them to teach these students effectively. The results
      highlight the need for increased emphasis on the unique educational requirements
      of students with hearing loss in teacher education programs, and for the
      provision of appropriate supports for both teachers and students to promote
      successful inclusion.

PMID- 23858705
TI  - One size does not fit all: individualized instruction in a standardized
      educational system.
AB  - This essay is based on a keynote address, "A Tour of the Horizons," presented to
      the 2012 annual conference of the Association of College Educators/Deaf and Hard
      of Hearing (ACE/DHH), held in Atlantic Beach, Florida.

PMID- 23858706
TI  - [Regulation of the Z ring positioning in bacterial cell division--a review].
AB  - The regulatory mechanism of bacterial cell division has long been a research
      focus. Forming a septum at the middle of the cell, the seemingly simple process
      is involved by multiple regulation factors. Zring (FtsZ ring) is the skeleton of
      the splitting complex. The locus where Z ring is formed is not only the position
      the septum formed but also determines the cell division site. Formation of Zring
      in the incorrect location results in inequality cell division. Several cell
      division regulation systems have been identified, including the Min system,
      nucleoid occlusion and the MipZ protein which effectively prevent Zring assembly
      by different mechanisms, ensuring formation of the fission complex at the correct
      position. Recent progresses about the formation process of Zring and regulation
      mechanism affecting the Z-ring positioning are summarized.

PMID- 23858707
TI  - [Production of L-lactic acid from pentose by a genetically engineered Escherichia
      coli].
AB  - OBJECTIVE: In this study, we constructed a recombinant Escherichia coli strain
      for the production of high-purity L-lactic acid, using a homoethanol fermenting
      mutant E. coli SZ470 (deltafrdBC deltaldhA deltaackA deltafocA-pflB deltapdhR:
      :pflBp6-pflBrbs-aceEF-lpd) as the starting strain. METHODS: By using homologous
      recombination, we deleted the adhE gene from SZ470 to obtain a mutant Escherichia
      coli JH01, which could not grow under anaerobic conditions. Then we cloned the L
      lactate dehydrogenase gene (ldhL) of Pediococcus acidilactici and inserted it
      into the chromosome of JH01 via electroporation to obtain a recombinant strain
      Escherichia coli JH12. We evaluated the L-lactic acid production of the
      recombinant strain in a 15 L fermenter. RESULTS: In 10 L LB medium supplemented
      with 6% glucose, JH12 maintained maximal cell growth and an efficient L-lactic
      acid production rate for 36 h. Glucose consumption rate achieved was 1.46 g/(L x
      h) and L-lactic acid production rate was 1.14 g/(L x h). The results also show
      that 41.13 g/L lactic acid was produced, achieving a purity of 95.69% (based on
      total fermentation products). Xylose consumption rate was 0.88 g/(L x h) and L
      lactic acid production rate was 0.60 g/(L x h). The production of lactic acid was
      34.73 g/L, achieving a purity of 98%. There were no succinic acid and formic acid
      detected and only little amount of acetic acid generated during the fermentation.
      CONCLUSION: We constructed a homolactic acid fermentation strain E. coli JH12,
      which could efficiently convert glucose and xylose into high-purity L-lactic
      acid. JH12 could have great potential in industrial fermentation for L-lactic
      acid production.

PMID- 23858708
TI  - [Transcript profile of converting xylose and glucose to ethanol by Candida
      shehatae].
AB  - OBJECTIVE: We detected and analyzed transcript profile differences between hexose
      and pentose fermentation by Candida shehatae, a typical xylose fermenting yeast
      strain. On this basis, the encoding genes of key enzymes and functional protein
      were screened for discovering candidates of metabolism and regulation. METHODS:
      To discover the key genes of xylose metabolism and ethanol fermentation in
      Candida shehatae, we performed a new high throughout de novo transcriptome
      sequencing technology on Roche 454 GS FLX Titanium platform. Two cDNA libraries
      were constructed and sequenced for xylose and glucose fermentation for comparison
      of its expressed sequence tags differences. RESULTS: Second sequencing run
      resulted in 600000 reads with the average length of 400bp for each cDNA library.
      We got 7250 and 7168 contigs by assembly, and annotated 2412 and 2456 unique
      genes by BLAST and Gene Ontology analysis for xylose and glucose respectively. By
      comparison, we identified 158 genes as different expression genes candidates at p
      < 0.05 for xylose metabolism and ethanol fermentation in Candida shehatae.
      CONCLUSIONS: The group genes for xylose metabolism and ethanol fermentation in
      Candida shehatae was discovered by using transcript profile sequencing and
      comparison. It will provide fundamental data for the relative research on
      molecular biology and metabolic regulation.

PMID- 23858709
TI  - [Correlation between thermostability of the xylanase EvXyn11(TS) and its N
      terminal disulfide bridge].
AB  - OBJECTIVE: To reveal the correlation between thermostability of xylanase
      EvXyn11(TS) and its N-terminal disulfide bridge, an EvXyn11(TS)-encoding gene
      (Syxyn11) was synthesized and subjected to site-directed mutagenesis. METHODS:
      Multiple homology alignment of protein primary structures between the EvXyn11(TS)
      and several GH family 11 xylanases displayed that, in their N-termini, only
      EvXyn11(TS) contained a disulfide bridge (Cys5-Cys32), whose effect on the
      xylanase thermostability was predicted by molecular dynamics simulation. We
      constructed a gene Syxyn11(M), encoding the mutated xylanase (EvXyn11(M)) without
      N-terminal disulfide bridge. Then, Syxyn11 and Syxyn11(M) were expressed in
      Pichia pastoris GS115, and temperature and pH properties of the expressed enzymes
      were analyzed. RESULTS: The analytical results displayed that the temperature
      optimum of EvXyn11(M) was 70 degrees C, which was 15 degrees C lower than that of
      EvXyn11(TS). The half-life (t1/2(90)) of EvXyn11(TS) at 90 degrees C was 32 min,
      while the t1/2(70) of EvXyn11(M) at 70 degrees C was only 8.0 min. CONCLUSION:
      The important role of the N-terminal disulfide bridge on the thermostability of
      EvXyn11(TS) was first predicted by molecular dynamics simulation, and confirmed
      by site-directed mutagenesis. This work provided a novel strategy to improve
      thermostabilities of the mesophilic family 11 xylanases with high specific
      activities.

PMID- 23858710
TI  - [Genes for cellulose-degradation and their expression conditions in Chaetomium
      globosum NK102].
AB  - OBJECTIVE: Use of renewable plant biomass is an active area in current
      biotechnology research. This report explores the cellulose-degradation system and
      the factors affecting cellulase gene expression in Chaetomium globosum NK102.
      METHODS: In the sequenced genome, we identified 10 cellulase genes by sequence
      homology alignment. We used a high-throughput sequencing technology (RNA-Seq) to
      monitor the differential expression of the genes under different culture
      conditions. RESULTS: We observed that cellulase activity increased with time in
      the fungal cultures. Accordingly, transcription of the genes encoding
      cellobiohydrolase, cellobiose dehydrogenase and endoglucanase (cbh1, cdh and
      eglI) was higher than the others. Expression of the transcriptional repressors,
      ACE I and CreA, decreased with the time, whereas expression of Hap2/3/5 complex
      was upregulated. In different carbon sources, cellulase activity and their gene
      transcription were repressed by glucose and were activated by cellobiose.
      Sorbitol had no significant effect. Interestingly, light affected positively the
      expression of these cellulase genes. CONCLUSION: Differential RNA-seq analysis
      can make preliminary exploration on the expression regulation of cellulase genes.
      Expression of the genes in C. globosum was determined by different culture
      conditions. This study has shown a molecular system of cellulose-degradation in
      C. globosum and provides information for interpretation of carbohydrate
      metabolism.

PMID- 23858711
TI  - [Cloning, expression and characterization of alcohol dehydrogenase and aldehyde
      dehydrogenase from Bacillus pseudofirmus OF4].
AB  - OBJECTIVE: To clone and characterize the alcohol dehydrogenase (ADH) and aldehyde
      dehydrogenase (ALDH) from Bacillus pseudofirmus OF4. METHODS: Genes of adh and
      aldh were cloned by PCR; expression vectors pET-Ahd and pET-Aldh were constructed
      and expressed in Escherichia coli BL21 (DE3). After Ni-NTA column chromatography
      purification, the protein was characterized. RESULTS: The optimal temperature and
      pH of ALDH was 35 degrees C and 8.0, the specific activities of ALDH was 979.6
      U/mg protein, the thermostability at 25 degrees C and 35 degrees C was better
      than at 45 degrees C. Although the expression level of ADH was too low to purify,
      but it was found that ADH had high catalytic activities by experiments of co
      expression and ethanol tolerance. CONCLUSION: Adh and aldh from B. pseudofirmus
      OF4 were cloned successfully. Co-expression of double genes could greatly
      increase the host strain on ethanol tolerance.

PMID- 23858712
TI  - [Identification and function test of an alkali-tolerant denitrifying bacterium].
AB  - OBJECTIVE: We obtained an alkali-tolerant denitrifying bacterium, and determined
      its denitrifying activity and alkali-tolerance. METHODS: An alkali-tolerant
      denitrifying bacterial strain was obtained by isolation and purification. We
      identified the bacterial strain by morphological observation, physiological test
      and 16S rRNA analysis. We determined the denitrifying activity and alkali
      tolerance by effects of initial nitrate concentration and initial pH on
      denitrification. RESULTS: An alkali-tolerant denitrifier strain R9 was isolated
      from the lab-scale high-rate denitrifying reactor, and it was identified as
      Diaphorobater nitroreducens. The strain R9 grew heterotrophically with methanol
      as the electron donor and nitrate as the electron acceptor. The nitrate
      conversion was 93.25% when strain R9 was cultivated for 288 h with initial
      nitrate concentration 50 mg/L and initial pH 9.0. The denitrification activity
      could be inhibited at high nitrate concentration with a half inhibition constant
      of 202.73 mg N/L. Strain R9 showed a good alkali tolerance with the nitrate
      removal rate at pH 11.0 remained 86% of that at pH 9.0. CONCLUSION: Strain R9 was
      identified as Diaphorobater nitroreducens, and it was an alkali-tolerant
      denitrifying bacterium with optimum pH value of 9.0.

PMID- 23858713
TI  - [Influence of different prey strains on isolation myxobacteria in saline-alkaline
      soils of Xinjiang].
AB  - OBJECTIVE: We isolated myxobacteria in saline-alkaline soils of Xinjiang using a
      prey-predator strategy where the prey bacteria can induce the predator
      myxobacteria to form visible fruiting body, and evaluated intrinsic relationships
      between prey and predator myxobacteria. METHODS: Sixteen bacteria with inductive
      effects of fruiting body formation were obtained, and then used as preys to
      isolate the myxobacteria. RESULTS: A total of 55 myxobacteria strains were
      isolated from 25 soil samples, which were identified to the genera of Myxococcus,
      Corallococcus, Pyxidicoccus, Cystobacter, and Nannocystis. Besides, 6 unpurified
      isolates were believed to be myxobacteria. All the 16 prey bacteria had
      preferable inductive effects on Myxococcus spp., whereas Pyxidicoccus spp. and
      Cystobacter spp. were only induced by Gram-positive strains. CONCLUSION: The prey
      predator strategy provided a new and more effective way to isolate myxobacteria.

PMID- 23858714
TI  - [Comparative proteomics analysis of extracellular proteins from Listeria
      monocytogenes and its isogenic prfA deletion mutant].
AB  - OBJECTIVE: Positive regulatory factor A (PrfA) protein plays a key role in the
      pathogenicity of Listeria monocytogenes by regulating the expression of virulence
      genes. We studied the regulation functions of PrfA and its role in Listeria
      monocytogenes (Lm) virulence. METHOD: Extracellular proteins were obtained from
      the supernatants of parental strain LM4 and mutant strain LM4deltaprfA cultured
      in minimal medium. We used two-dimensional gel electrophoresis and matrix
      associated laser dissociation/ionization time of flight mass spectrometry (MALDI-
      TOF-MS) to analyze the differences of secreted proteins between LM4 and
      LM4deltaprfA. RESULTS: The electrophoresis results show that 31 different spots,
      19 spots corresponding 12 proteins were identified by MALDI- TOF-MS. Some
      virulence related proteins were verified, such as InlC, ActA and LLO. Some new
      proteins that are regulated by PrfA include D-alanyl-D-alanine carboxypeptidase,
      dipeptide Glycine and Trytophan (GW) repeat-containing surface protein,
      transcriptional regulator and some hypothetical proteins with unknown functions.
      Real-time quantitative PCR was conducted to verify the proteomics results. The
      mRNA expression level of hly, actA and inlC gene was significantly reduced, and
      that of D-alanyl-D-alanine carboxypeptidase and GW repeat-containing surface
      protein's synthesis also had a reduction in LM4deltaprfA strain. CONCLUSION: PrfA
      plays key roles on the regulation of genes in LIPI- I and LIPI- II.

PMID- 23858716
TI  - [Characterization of a probiotic Lactobacillus strain isolated from oral cavity].
AB  - OBJECTIVE: From oral cavity we isolated and characterized probiotic lactobacilli
      that could probability be applied to therapy and prevention of oral diseases.
      METHODS: Lactobacillus strains were isolated by plating the saliva and dental
      plaque of healthy donors on selective medium. Then the target strains were tested
      for inhibiting the growth of a Streptococcus mutans strain belonging to
      cariogenic pathogen species. Other properties such as production of extracellular
      polysaccharide and resistance to the antibacterial substances were also
      investigated. RESULTS: Lactobacillus fermentum Y29, a strain with antimicrobial
      activity against Streptococcus mutans, was obtained from dental plaque. This
      strain was an extracellular polysaccharide producer, which corresponds to its
      aggregation ability. Moreover, L. fermentum Y29 showed resistance to 1.0 mg/mL
      lysozyme and 140 microg/g hydrogen peroxide that may guarantee its persistence in
      the complex oral niche. CONCLUSION: Probiotic properties were characterized of an
      oral isolate L. fermentum Y29, which provided a possibility for its application
      in prevention and treatment of oral diseases.

PMID- 23858715
TI  - [Construction of cell surface display system in lactic acid bacteria by using ice
      nucleation protein].
AB  - OBJECTIVE: The gene of ice nucleation protein (INP), an outer membrane of
      Pseudomonas syringae was tested to display foreign proteins on the surface of
      Lactococcus lactis. METHODS: Plasmids pHZ101 and pHZ102 were constructed using
      gfp (Green Fluorescence Protein) as the reporter gene and N-terminal and NC
      terminal of inp as the anchoring units. Plasmids pHZ101 and pHZ102 were
      subsequently transformed into Escherichia coli JM109 and Lactococcus lactis
      MG1363. RESULTS: Fluorescence microscope shows that green fluorescence was
      observed in both recombinant E. coli and L. lactis strains. Western blot
      indicated that GFP was expressed in both recombinant E. coli and L. lactis
      strains. INPN-GFP was mostly trapped in cytoplastic fraction while INPNC-GFP was
      mainly targeted on the cell membrane of L. lactis. CONCLUSION: The results
      suggest a new way to construct cell surface display system of lactic acid
      bacteria by using ice nucleation protein.

PMID- 23858717
TI  - [Sequencing the complete genome of rabies virus CVS-11 strain and constructing
      its full-length infectious cDNA clone].
AB  - OBJECTIVE: To sequence the complete genome of CVS-11 strain and establish a
      reverse genetic system of CVS-11 to further study its pathogenic mechanism,
      virulence genes and antigenic sites. METHODS: We amplified12 fragments covering
      the complete genome of the CVS-11 strain by RT-PCR, and then cloned to pEASY
      Blunt vector for sequencing the complete genome of CVS-11. We analyzed single
      restriction enzyme sites of the full length cDNA of the CVS-11 strain by DNAMAN
      and designed 4 pairs of specific primers. We amplified the full-length cDNA of
      CVS-11 by RT-PCR. We obtained four fragments and cloned into pcDNA3. 1. We named
      the full-length cDNA plasmid pcDNA3. 1-CVS-11. We also cloned helper plasmids
      pcDNA3.1-N, P, L and G expressing N, P, L and G protein of CVS-11 strain,
      respectively. We co-transfected NA cells with the full-length plasmid and four
      helper plasmids. We identified the supernatant of the transfected and then
      passaged NA cells by immunofluorescence staining and RT-PCR and found the
      recombinant virus rCVS-11 rescued successfully. RESULTS: Sequencing results
      showed that the complete genome of CVS-11 was composed of 11 927 nucleotides. The
      complete genome of CVS-11 encoded 5 structure proteins and gene array was the
      same as other reported rabies viruses. We successfully constructed a reverse
      genetic system of CVS-11, namely the full length plasmid pcDNA3. 1-CVS-11 and 4
      help plasmids pcDNA3. 1-N, P, L, G and rescued the rCVS-11 from a full-length
      infectious cDNA clone. CONCLUSION: The reverse genetic system of the CVS-11
      strain laid the foundation for future studies on rabies virus.

PMID- 23858718
TI  - [The expression of NOD1 and NOD2 and the regulation of glucocorticoids on them in
      allergic rhinitis].
AB  - OBJECTIVE: To investigate the expression of NOD1 and NOD2 in the nasal mucosa of
      healthy individuals and allergic rhinitis(AR), and explored the regulation of
      glucocorticoids on them. METHOD: RT-PCR and immunohistochemistry were used to
      detect the expression of NOD1 and NOD2 in nasal mucosa from healthy control and
      AR. Nasal explant culture was used to explore the effect of glucocorticoids on
      NOD1 and NOD2 expression. RESULT: NOD1 and NOD2 mRNA expression level was
      significantly increased in AR compared with control. Immunohistochemical staining
      demonstrated that NOD1 and NOD2 were mainly expressed by epithelial cells and
      some unknown cells in lamina propria and there were significantly more positive
      staining cells were observed in AR tissue when compared with control.
      Glucocorticoids down-regulated NOD1 and NOD2 expression in AR. CONCLUSION: NOD1
      and NOD2 as two PRRs may take part in the pathogenesis of AR, glucocorticoids may
      play a therapeutical role on allergic rhinitis through down-regulated the
      expression of NOD1 and NOD2.

PMID- 23858719
TI  - [The serum level transformation of IFN-gamma, IL-4 and IgE before and after SIT
      in patients with allergic rhinitis].
AB  - OBJECTIVE: To assess the efficacy and the transformation of IFN-gamma, IL-4,
      total IgE and specific IgE before and after specific immune therapy(SIT) in
      patients with allergic rhinitis. METHOD: The subjective symptom and levels of IFN
      gamma, IL-4, total IgE and specific IgE were observed in 40 patients with
      allergic rhinitis before and after SIT. RESULT: Total effective rate in patients
      after SIT was 85%. There's no significant difference between the levels of
      specific IgE before and after SIT(P>0.05) ,while the levels of IL-4 and total IgE
      were significantly lower, the levels of IFN-gamma were significantly higher pre
      than that of post SIT. CONCLUSION: SIT is safe and effective,and can regulate the
      levels of IFN-gamma, IgE and IL-4. But the role of specific IgE in SIT is still
      unknown.

PMID- 23858720
TI  - [Imaging characteristics of CT, MRI of tumors involving skull base in the
      parapharyngeal space].
AB  - OBJECTIVE: To discuss imaging characteristics of CT, MRI of tumors involving
      skull base in the parapharyngeal space,maximatily limit and improve the diagnosis
      rate of tumors involving skull base in the parapharyngeal space. METHOD: Thirty
      one patients with tumors involving skull base in the parapharyngeal space treated
      in our department were collected and reviewed. All the patients have pathological
      diagnosis and were examined by CT and/or MRI. To explore shape of tumor, its
      relation with surrounding structures, CT shows density size and the MRI signal
      directly through retrospective analysis of imaging characteristics of CT, MRI.
      RESULT: In all the 31 cases, 19 tumors were schwannoma, 8 tumors were mixed tumor
      of salivary gland, 2 tumors were carotid body tumor. 2 tumors were nasopharyngeal
      carcinoma involving skull base. Schwannomas and salivary gland mixed tumor can be
      expressed as round or oval with periphery smooth, and had intact capsule. The
      tumors had necrosis, sac variable area. Pleomorphic adenoma are all derived from
      deep parotid. Schwannoma had clear boundary with deep parotid. The effect of
      cavum nasopharyngeal and cavum oropharyngeal is relevant to tumor sizes and
      locations. Imaging characteristics of CT, MRI for carotid body tumor show soft
      tissue mass with attenuation similar to that of muscle. CT enhancement scan show
      intense enhancement. MRI show imaging of flowing empty vein. Imaging
      characteristics of MRI for nasopharyngeal carcinoma involving skull base in the
      parapharyngeal space show oval mass with low density signal, T1WI enhancement
      scan show necrosis, sac variable area. CONCLUSION: CT and MRI could provide the
      position, size, boundary of the tumor and its relationship with cervical blood
      vessels well, which were important to operation schemes. CT and MRI before
      operation are valuable to the treatment of PPS tumors.

PMID- 23858721
TI  - [Comparison of serum specific IgE and skin prick test in allergic rhinitis
      patients sensitive to dust mite].
AB  - OBJECTIVE: To investigate the correlation of serum specific IgE and skin prick
      test in allergic rhinitis patients sensitive to dust mite and the difference
      between the results. METHOD: Data of 349 allergic rhinitis patients who had
      positive result in either Dermatophagoides pteronyssinus(Der p) or
      Dermatophagoides farinae (Der f) by serum specific IgE and skin prick test were
      statistically analyzed. RESULT: Grades of Skin prick test and specific IgE levels
      were notably relevant in these two dust mites(Der p r= 0. 568, Der f r= 0. 506,
      P<0. 01). There was significant difference of positive rates between serum
      specific IgE and skin prick test in Der p(Chi2 = 11. 605, P<0. 01)but not in Der
      f(Chi2 =0, P>0.05). There was no correlation between positive degree of two
      methods and score of clinical symptoms in allergic rhinitis. CONCLUSION: Serum
      specific IgE and skin prick test were notably relevant in allergic rhinitis
      patients sensitive to dust mites. The positive rates of the two methods were
      different due to different allergen. Therefore, they could not substitute for
      each other. The level of serum specific IgE and positive degree of skin prick
      test could not reflect the degree of symptom in allergic rhinitis.

PMID- 23858722
TI  - [The expression of Smac and survivin in sinonasal inverted papilloma].
AB  - OBJECTIVE: To explore the expression of Smac(second mitochondria-derived
      activator of caspase)and survivin on the growth, development, recurrence and
      carcinogenesis of the sinonasal inverted papilloma(NIP). METHOD:
      Immunohistochemical method was used to detective the expression of Smac and
      survivin in 10 cases of (nasal cavity mucosae, NM), 45 cases of NIP. The NIP
      group including 25 cases of NIP without dysplasia, 11 cases of NIP with
      dysplasia, and 9 cases of NIP with malignant transformation to squamous cell
      carcinoma(SCC). RESULT: The intensity of the positive expression of Smac in NIP
      was lower than NM, the intensity of the positive expression decreased with the
      decreasing degree of histological differentiation. There was significantly
      difference between NIP without dysplasia and SCC. The expression of survivin was
      negative in the control group, the expression intensity of NIP was enhanced. The
      degree of histological differentiation was lower, the intensity of the positive
      expression was higher. The expression between NIP without dysplasia and SCC had
      significantly differences. Smac negatively correlated with survivin(rs = -0.403,
      P<0.01). CONCLUSION: Smac and survivin were associated with the growth and
      carcinogenesis of NIP.

PMID- 23858723
TI  - [Carcinoembryonic antigen increased as initial manifestation of medullary thyroid
      cancer (report of 2 cases and review of the literature)].
AB  - OBJECTIVE: To raise clinical awareness of carcinoembryonic antigen(CEA) increased
      as initial manifestation of medullary thyroid cancer(MTC) and explore the
      diagnosis and treatment. METHOD: Clinical data of 2 cases CEA increased as the
      initial presentation of MTC were retrospectively analyzed and clinical
      manifestations of the disease, diagnosis, treatment were also discussed by
      literature reviewing. RESULT: Two patients received thyroid ipsilateral lobe
      total resection, MTC was confirmed by intraoperative frozen pathology, re-total
      resection of the contralateral lobe and bilateral VI lymph node dissection were
      performed. Lymph nodes had no metastasis confirmed by pathological frozen
      examination. CEA returned to normal within 2 months after surgery. No tumor
      recurrence and metastasis were found after follow-up for 3 to 24 months.
      CONCLUSION: CEA increased as the initial presentation MTC was rare and clinical
      identification of CEA increased disease should be taken into account the MTC as
      possible. Total thyroidectomy and bilateral VI lymph node dissection was the main
      surgical treatment for it.

PMID- 23858724
TI  - [Effect of septoplasty on the modality of inferior turbinate: a CT study].
AB  - OBJECTIVE: To explore the effect of septoplasty on the modality of inferior
      turbinate in patients with a deviated nasal septum. METHOD: Twenty-three patients
      with nasal septum deviation underwent septoplasty without turbinate surgery. All
      patients underwent CT imaging scans before and 3 months after the surgery. The
      thicknesses of the medial mucosa, lateral mucosa,and the cross-sectional areas of
      the inferior turbinate were measured and compared using the Wilcoxon signed rank
      test. P<0. 05 was considered statistically significant. RESULT: On the concave
      side of the septum, the thickness of the medial mucosa of the inferior turbinate
      was(5. 3+/-1.5) mm to (4. 1+/-1. 2) mm (P<0. 05), the thicknesses of the lateral
      mucosa of the inferior turbinate was(2. 5+/-0. 9) mm to (2.0+/-0. 9) mm (P>0.
      05), and the cross-sectional area of the inferior turbinate was(139. 8 +/- 35.6)
      mm2 to( 110. 3 +/- 22.6)mm2 (P<0.05), pre- and post-operatively. On the convex
      side of the septum , the thickness of the medial mucosa of the inferior turbinate
      was(1.0 +/- 0. 6) mm to(4. 3 +/- 0. 6) mm (P>0. 05), the thicknesses of the
      lateral mucosa of the inferior turbinate was(1. 9+/-1. 1) mm to (1. 9+/-1.3) mm
      (P>0. 05), and the cross-sectional area of the inferior turbinate was(104. 5+/
      15. 8)mm2 to(108. 3 +/- 20. 8)mm2 (P>0. 05), pre- and post-operatively.
      CONCLUSION: The compensatory hypertrophic inferior turbinate may be self
      adaptability in modality soon after septoplasty, thus surgeons must take it into
      consideration before performing turbinate surgery.

PMID- 23858725
TI  - [The study of methodology and reference values for cellularity of nasal lavage of
      normality].
AB  - OBJECTIVE: To study the reference values for differential cell counts in nasal
      lavage of normality in Nanjing. METHOD: The total and differential cell counts
      were examined in nasal lavage from samples of a total of 300 healthy non-smoking
      adult volunteers. RESULT: Nasal lavage succeeded in 281 subjects, the achievement
      ratio was 93.67%. The proportions of eosinophils 0.46 +/- 1.03, neutrophils were
      4.46 +/- 9. 84, macrophages 0. 19 +/- 0.73 and lymphocytes 0.04 +/- 0. 16,
      respectively. There were no significant differences in the differential cell
      counts between male and female(P>0. 05) . The 95% ceiling percentile of
      eosinophils and neutrophils in nasal lavage are 2. 58 and 19.76 respectively.
      CONCLUSION: The reference values were established for differential cell counts in
      nasal lavage of normality in Nanjing. We propose that these data be used in
      research on pathogenesis, diagnosis and treatment of the patients with nasal
      inflammation.

PMID- 23858726
TI  - [Effects of the inhibition and apoptosis by shRNA mediated survivin gene
      silencing in xenograft tumor of nasopharyngeal carcinoma cell CNE-2].
AB  - OBJECTIVE: To observe wether pSIREN-survivin/shRNA can induce the apoptosis and
      inhibit it's growth of nude mice xenograft tumor of nasopharyngeal carcinoma
      cell. METHOD: Subcutaneous tumors in athymic mice were induced by inoculation of
      NPC and divided into the blank group A, the negative group B,the experimental
      group C randomly. PBS,the negative and positive pSIREN-survivin/shRNA were
      injected into the subcutaneous tumors poly site. The inhibition ratio was
      measured by the tumor size calculation after inoculation. The expression of
      survivin in the xenograft tumor was observed by RT-PCR and immunohistochemistry.
      The cell apoptosis in tumor tissues was detected by TEM. The liver and kidney
      function was tested by blood routine test. RESULT: The inhibition ratio of group
      C and group B was (52. 11 +/- 1. 03)%, (2. 15 0. 11)% respectively, the
      inhibition rate in expression level of survivin mRNA was (77. 5+/-2. 03) %, (1.
      39+/-0. 14) % respectively. The dyeing of survivin was more shallow in group C,
      the intensity is also less than group B. Nuclear chromatin was deepened, split
      into pieces, flake, and nuclear membrane was surrounded to edge. Cytoplasmic
      color and density were deepened, and organelles such as mitochondria was
      disappeared, the microscopic changes of cellular apoptosis at the earlier stage
      were watched, the difference of the function in liver and kidney was not
      statistically in statistical. CONCLUSION: The expression of survivin in xenograft
      tumor was significantly inhibited by pshRNA-survivin/shRNA,the apoptosis of tumor
      cells was accelerated and the growth speed of NPC cells in xenograft tumor was
      retarded. The high expression of nasopharyngeal carcinoma's gene could
      significantly be silenced by using technology of RNAi, the growth of tumors could
      be inhibited also. Its a novel treatment that have a good prospect.

PMID- 23858727
TI  - [The effects of tea polyphenols and Laminaria japonica polysaccharides on
      nasopharyngeal carcinoma cell HONE1 and CNE2].
AB  - OBJECTIVE: To explore the effects of laminaria japonica polysaccharides(LJP) and
      tea polyphenols (TP) on nasopharyngeal carcinoma(NPC) cells HONE1 and CNE2, and
      further to explore the underlying mechanism of antitumor activity of LJP on NPC
      cell in vivo. METHOD: To identify the logarithmic growth phase of NPC cells HONE1
      and CNE2 through cell growth curve and doubling time by means of MTT, then
      inhibition of the cells proliferation were detected with LJP and TP separately
      and combined. With LJP treatment, cell apoptosis of HONE1 was examined by double
      staining assay. A tumor model,established by subcutaneously inoculation of NPC
      cell HONE1 into nude mice,was used to evaluate the inhibitory effect of LJP in
      vivo. RESULT: Both LJP and TP had inhibition effect on two groups of cell
      proliferation, and LJP and TP combined effect of inhibition were higher than the
      two separate on two sets of experimental cell proliferation, whose effect was
      concentration-dependent. LJP could induce apoptosis of HONE1. With the increasing
      concentration of LJP, apoptosis rate increased. The apoptosis rate was(49.51 +/-
      1. 89) % (P<0. 01) when treated with 320 mg/L LJP. The inhibition rate was
      between 50% to 60% at 72 h after treatment with 320 mg/L LJP. Compared to control
      group, the growth of xenografts in nude mice was significantly suppressed after
      administration of LJP at a dose-dependent manner. The inhibition rates were 33.
      7%(P<0. 05)and 47. 0%(P<0. 01) when treated with 25.0 mg/kg and 50. O mg/kg
      respectively. Whereas the inhibition rate of 12.5 mg/kg group was only 16.
      4%(P>0. 05). CONCLUSION: LJP and TP can inhibit the proliferation of NPC cells
      HONE1 and CNE2 respectively,and combined use has a significant effect. LJP can
      inhibit the growth of NPC probably by inducing apoptosis of NPC cells in vitro
      and in vivo.

PMID- 23858728
TI  - [Experimental model of facial paralysis by nerve compression in primates
      (Callithrix sp.): A new model of facial paralysis in small nonhuman primates].

PMID- 23858729
TI  - [Non-surgical treatment for adenoidal hypertrophy].
AB  - OBJECTIVE: Study the practicability of non-surgical treatment for adenoidal
      hypertrophy. METHOD: Fifty-seven children were recruited in a randomized,placebo
      controlled trial. Group T1 underwent intranasal corticosteroids treatment, group
      T2 underwent leukotriene receptor antagonists treatment, group C underwent
      placebo treatment:the records of 3 groups were analyzed. RESULT: After a 12-week
      treatment with intranasal corticosteroids or leukotriene receptor antagonists,
      group T1 and T2 patients demonstrated significant improvements in clinical
      symptoms and a more-pronounced reduction in adenoid size compared with control
      group patients, the difference was statistically significant. No statistically
      significant difference in group T1 and T2 patients. CONCLUSION: Intranasal
      corticosteroids and leukotriene receptor antagonists may be considered useful in
      decreasing adenoid pad size and the severity of symptoms related to adenoidal
      hypertrophy. Children with adenoidal hypertrophy should be considered for non
      surgical treatment before surgery is planned.

PMID- 23858730
TI  - [The study and clinical application of tongue-fixer].

PMID- 23858731
TI  - [Effects of magnesium sulfate combined with sodium chloride concentrated diluted
      solution nasal irrigation for endoscopic sinus operation of intraoperative
      bleeding and pain].

PMID- 23858732
TI  - [Inflammatory myofibroblastic tumor in left maxillary sinus: analysis of a case
      with misdiagnosis].

PMID- 23858733
TI  - [Multiple subcutaneous Rosai-Dorfman disease involved nasal and pharyngeal
      cavity: a case report].
AB  - Although Rosai-Dorfman disease is a rare disorder characterized by proliferation
      of distinctive histiocytes within lymph node sinuses and lymphatics, sometimes
      involving extranodal sites, the nasal cavity and pharyngeal cavity are rarely
      involved additional. In this report, a 22-year old man with multiple subcutaneous
      lumps and submucosal lumps in bilateral nasal cavity and pharyngeal cavity is
      presented, which was diagnosed by nasopharyngeal endoscope,computed tomography
      scan and biopsy. The subcutaneous lumps were ablated and prednisone was accepted
      for three months as preventive therapy.

PMID- 23858734
TI  - [Progress in the treatment for thyroid microcarcinoma].
AB  - Thyroid microcarcinoma(TMC) refers to the diameter less than 1cm in thyroid
      cancer. In recent years, with high frequency ultrasound and pathology diagnosis
      technology development and improvement, the incidence of TMC increased
      dramatically. However, there are a lot of controversy about its complication,
      treatment methods and value of treatment both in domestic and abroad. In this
      paper,we review literatures in the passed 5 years both in domestic and abroad,
      and investigated the progress of treatment for TMC. Agreement on the view:
      routine central lymph node dissection should be done regularly in the treatment
      thyroid microcarcinoma.

PMID- 23858735
TI  - [Research progresses on the pathogenesis of bacterial biofilm in chronic
      rhinosinusitis].
AB  - The role of bacterial biofilms in the chronic diseases has been recognized more
      and more. The experts in the centers for disease control and prevention of the
      United States estimate that 65% of human bacterial infection is involved with the
      biofilms. In the recent study. it has been proved that there is a high
      correlation between the bacterial biofilm and the pathogenesis and prognosis of
      chronic rhinosinusitis(CRS). In order to elucidate the role of bacteria films in
      the pathogenesis of CRS, we reviewed various method of testing the bacterial
      biofilms in CRS, and summarized the related researches. Based on the detection
      researches and summaries, we conclude that bacterial biofilm can contribute to
      the continuance and development (diffusion and repeated) of CRS. It can lead to
      the continuous inflammation by influencing the immune system of the mucous
      membrane. While there is little research on the bacterial biofilm. Further
      researches will be needed for the exact mechanism of the bacterial biofilm in
      CRS. in order to find more effective therapeutic method and targets.

PMID- 23858736
TI  - [ART reconstruction from few views using bilateral-filtering iterative method].
AB  - An algebraic image reconstruction from few views using bilateral-filtering
      iterative method was proposed due to the problem of computed tomography
      insufficient data in the present study. In each iteration reconstruction, we
      first used algebraic reconstruction technique (ART) algorithm to reconstruct an
      image, ensuring the non-negativity of the reconstructed image at the same time,
      and then performed bilateral-filtering to the above-mentioned image. In order to
      improve reconstructed image quality and accelerate the convergence speed, we
      developed a modified bilateral-filtering method. Shepp-Logan simulation
      experiments and real CT projection data reconstructions showed the feasibility of
      the algorithm. The results showed that, compared with the traditional methods of
      filtered back projection (FBP), ART and GF-ART,the proposed method has a higher
      signal-to-noise ratio, and maintains more effectively the image edge information.

PMID- 23858737
TI  - [Design and implementation of controlling smart car systems using P300 brain
      computer interface].
AB  - Using human electroencephalogram (EEG) to control external devices in order to
      achieve a variety of functions has been focus of the field of brain-computer
      interface (BCI) research. P300 is experiments which stimulate the eye to produce
      EEG by using letters flashing, and then identify the corresponding letters. In
      this paper, some improvements based on the P300 experiments were made??. Firstly,
      the matrix of flashing letters were modified into words which represent a certain
      sense. Secondly, the BCI2000 procedures were added with the corresponding source
      code. Thirdly, the smart car systems were designed using the radiofrequency
      signal. Finally it was realized that the evoked potentials were used to control
      the state of the smart car.

PMID- 23858738
TI  - [Aging affects on the response irregularity of cells in different visual areas of
      cats].
AB  - In this research, we compared the visual neuron responses for LGN, A18 and PMLS
      of old and young cats with extracellular single-neuron recording techniques. We
      used firing rate vector to characterize information, and response irregularity of
      cells to evaluate the degeneration of visual characters. Response irregularity is
      characterized by means of the two coefficients of variation of firing rate
      vectors: Cv and Cv2. We found that there was no significant change of the
      response irregularity in LGN areas during the aging process from young to old
      cats. But in the other two areas, neurons of old cats exhibited significantly
      larger response irregularity than those of young cats. The result indicated that
      the information processing function of advanced visual cortex was impaired by
      aging. This result also provids a reference for the research of the other
      neuronal system changes during aging process.

PMID- 23858739
TI  - [Simulation analysis and experimental study of positioning signals in thorax
      electric field catheter].
AB  - In order to enhance the position accuracy of ablation catheter in heart
      electrophysiology operation, signals of respiration and heartbeat must be removed
      for subsequent data processing. Based on locating principle of electrical field
      with low frequency, synchronous detector with MC1496 has been developed in this
      study. In the present research, several methods are utilized to optimize the
      circuit performance, such as coupling and stopping direct current, low-pass
      filtering, as well as limiting ripple voltage etc. Through simulation results, it
      showed that the demodulation performance of the circuit was fine. Through
      simulation platform of thorax electric field and animal experiment, the circuit
      feasibility were further proved good for extracting signals of respiration and
      heartbeat.

PMID- 23858740
TI  - [Objective evaluation of driving fatigue by using variability of pupil diameter
      under spontaneous pupillary fluctuation conditions].
AB  - Objective evaluation of driver drowsiness is necessary toward suppression of
      fatigued driving and prevention of traffic accident. We have developed a new
      method in which we utilized pupillary diameter variability (PDV) under
      spontaneous pupillary fluctuation conditions. The method consists of three main
      steps. Firstly, we use a 90s long infrared video of pupillogram infrared
      sensitive CCD camera. Secondly, we employed edge detection algorithm based on
      curvature characteristics of pupil boundary to extract a set of points of visible
      pupil boundary, and then we adopted these points to fit a circle to obtain the
      diameter of the pupil in current frame of video. Finally, the values of PDV in
      90s long video is calculated. In an experimental pilot study, the values of PDV
      of two groups were measured. One group rated themselves as alert (12 men), the
      other group as sleepy (13 men). The results showed that significant differences
      could be found between the two groups, and the values were 0.06 +/- 0.005 and
      0.141 +/- 0.042, respectively. Taking into account of the knowledge that
      spontaneous pupillary fluctuation is innervated by autonomic nervous system which
      activity is known to change in parallel with drowsiness and cannot be influenced
      by subjective motive of people. From the results of the experiments, we concluded
      that PDV could be used to evaluate driver fatigue objectively.

PMID- 23858741
TI  - [Effects of 3-megapixel and 5-megapixel monitors on detecting micro-calcification
      in high- and low-resolution breast images].
AB  - To evaluate the influence of 3- and 5-megapixel medical professional monitors in
      detecting the micro-calcifications on high- and low-resolution breast images, we
      performed a retrospective study in low- (n = 100) and high-resolution (n = 100)
      data, including 40 micro-calcification patients in a group and 60 normal ones in
      control group respectively. Two doctors, one junior, and the other senior,
      reviewed all the images without knowing the clinical data and histology, and
      their observations of each image with different monitors were calculated. The
      areas under the ROC curves (Az) were compared. Finally, the interpretation
      consistency of the two doctors was assessed using Kappa analysis. In the low
      resolution data group, the two doctors' detection performance of breast micro
      calcifications were very similar in the 3M and 5M medical professional monitors
      (P = 0.451 and 0.559). In the high resolution group, however, the senior doctor's
      recognition rate on the 5M monitor was significantly higher than that on the 3M
      (P = 0.022), while the junior's recognition rate had no significant difference (P
      = 0.141) between the two readings. The two doctors' interpretation consistency on
      5M monitor was better than that on 3M monitor. For the high-resolution images on
      the 5M monitor, the interpretation of the two doctors had extremely great
      consistency (K = 0.862). Therefore, different breast images of different
      resolutions should match corresponding resolution monitor. Interpretation of high
      resolution images with 5M monitor has more advantages in the micro-calcification
      detection for senior doctors.

PMID- 23858742
TI  - [Research of movement imagery EEG based on Hilbert-Huang transform and BP neural
      network].
AB  - This paper introduces the characteristics of the Hilbert-Huang transform (HHT),
      and studies the classification of movement imagery EEG based on the HHT method
      and BP neural network. After preprocessed, the movement imagery EEG data were
      descomposed with empirical mode decomposition (EMD) into a series of intrinsic
      mode functions (IMFs). Then the low frequency IMFs were removed, and the rest of
      IMFs were conducted by Hilbert transform to get Hilbert marginal spectrum. The
      marginal spectrum subtracted values between the channal C3 and channal C4 were
      selected as the original features which were then decreased the dimension by the
      principal components analysis so as to be jointed with EEG complexity to
      construct the feature vector. The BP neural network was utilized to classify the
      EEG pattern of left and right hand motor imagery. The brain computer interface
      (BCI) competition II data set III was selected to carry out the discrimination,
      and the classification accuracy rate is up to 87.14%, which is a comparably good
      result and proves HHT to be a feasible and effective method on EEG analysis.

PMID- 23858743
TI  - [Study on correlations between CT perfusion parameters and tumor angiogenesis of
      cervical cancer].
AB  - This study was aimed to analyze the correlation between CT perfusion parameters,
      e. g. perfusion (PF), blood volume (BV), peak enhancement image (PEI), time to
      peak (TTP), and the microvessel density (MVD) of cervical cancer. CT perfusion
      scans were carried out in 31 patients with cervical cancer. After their surgical
      resections, we obtained 31 cases of cervical cancer specimens, and 15 cases of
      adjacent normal cervical specimens as control group, then these 46 specimens were
      used in MVD detection through immunohistochemical CD34 staining. The MVDs of the
      tumor group were significantly higher than those in the control group, and the
      former seems to increase with the clinical stages with a positive correlation.
      The PF and PEI values have positive correlations with corresponding MVD values.
      The PF value of squamous carcinoma group has correlation with corresponding MVD
      value. The PF and PEI values of poorly differentiated group have correlations
      with corresponding MVD values. The PF, PEI and BV values of II-III stage group
      are positively correlated with corresponding MVD values. The PF value of lymph
      metastasis or non-lymph metastasis group both have correlations with
      corresponding MVD values. We found that CT perfusion parameters were positively
      correlated with corresponding MVD values in cervical cancer. Our results suggest
      that CT perfusion is a new method which could reflect tumor angiogenesis,
      histological malignant grade, invasion, and clinical stage. It will help us
      determine the tumor staging and prognosis.

PMID- 23858744
TI  - [Feature extraction of myocardial infarction based on lead I ECG].
AB  - This paper presents a myocardial infarction feature extraction algorithm, and
      whereby using single-cycle signal of electrocardiogram (ECG) lead I, we solved
      the problem of inconvenience in using multi-lead ECG. Firstly, the noise is
      eliminated from the signal of ECG lead I, and then, wavelet packet algorithm is
      introduced to extract the main frequency band of QRS complex and T wave, and
      reconstruct the QRS complex and T wave shape so as to determine the original and
      end positions of ST segment. Finally, ST segment is decomposed and the waveform
      characteristics of myocardial infarction from ECG lead I signal is obtained based
      on the analysis of wavelet's multi-resolution. Simulation results showed that the
      algorithm achieved a high recognition rate, which provides fundamental principle
      for the detection of myocardial infarction by using the ECG lead I signal.

PMID- 23858745
TI  - [RSF model optimization and its application to brain tumor segmentation in MRI].
AB  - Magnetic resonance imaging (MRI) is usually obscure and non-uniform in gray, and
      the tumors inside are poorly circumscribed, hence the automatic tumor
      segmentation in MRI is very difficult. Region-scalable fitting (RSF) energy model
      is a new segmentation approach for some uneven grayscale images. However, the
      level set formulation (LSF) of RSF model is not suitable for the environment with
      different grey level distribution inside and outside the intial contour, and the
      complex intensity environment of MRI always makes it hard to get ideal
      segmentation results. Therefore, we improved the model by a new LSF and combined
      it with the mean shift method, which can be helpful for tumor segmentation and
      has better convergence and target direction. The proposed method has been
      utilized in a series of studies for real MRI images, and the results showed that
      it could realize fast, accurate and robust segmentations for brain tumors in MRI,
      which has great clinical significance.

PMID- 23858746
TI  - [Evaluation of anomalous pulmonary venous connection: comparison between dual
      source CT and echocardiography].
AB  - This paper is to compare dual-source computed tomography (DSCT) with trans
      thoracic echocardiography (TTE) in the evaluation of anomalous pulmonary venous
      connection (APVC) to explore the advantages of DSCT. Thirty-one patients with
      APVC detected by DSCT were enrolled in this study. In this cohort, 16 patients
      underwent echocardiography followed by operative treatments; and among the
      remained 15 patients who did not received surgical treatment, echocardiography
      was performed in 10 patients. The numbers and drainage sites of anomalous
      pulmonary veins, and accompanied defects on DSCT and TTE were retrospectively
      analyzed. In terms of diagnosis of the numbers and the drainage sites of
      anomalous pulmonary veins, the accuracy of DSCT was 98% (49/50) and 93.8%
      (15/16), while the accuracy of echocardiography was 80% (40/50) and 56.3% (9/16),
      respectively. There were statistical differences between the two modalities (P <
      0.05). Although the detection rates of accompanied defects were 89.1% (41/46) and
      78.3% (36/46) for DSCT and echocardiography, respectively, no statistically
      significant difference was found between the two modalities (P > 0.05). The 15
      patients without receiving surgical treatments were partial APVC confirmed by
      DSCT, but APVC was found in 40% (4/10) patients by echocardiography. In
      conclusion, DSCT could be superior to evaluating APVC in comparison with
      echocardiography, and should be recommended as an important procedure for
      preoperative assessment of the anomaly in patients with APVC.

PMID- 23858747
TI  - [Study on multi-level fractal features extraction method of breast mass].
AB  - Breast mass is women's common disease, and it seriously affects the health of
      women. Accurate detection and location of the mass will greatly improve the
      precision of the diagnosis of the breast disease. Studies have shown that the
      organizational structure and surface roughness of the mass constitute the texture
      features of mass and it is an important basis for distinguishing the mass. In
      this paper, a multi-level fractal features extraction method is proposed, and,
      moreover, the fractal feature vector of the suspicious lesions has been
      established, thus realizing the feature extraction and analysis of the mammary
      gland. Finally, the result of classification with the support vector machine
      (SVM) was given. 110 mammograms are extracted and classified with an accuracy of
      90%. The results showed that the multi-level fractal features extraction and
      classification methods proposed in this paper could improve the accuracy of mass
      detection and could be effective for the early diagnosis of the disease.

PMID- 23858748
TI  - [Contrast-enhanced MSCT features and predominant anatomic distribution of
      mediastinal tuberculous lymphadenitis].
AB  - We retrospectively analyzed the features of the size, morphology, attenuation,
      the enhancement patterns, and anatomic distribution of 45 patients with
      mediastinal tuberculous lymphadenitis shown on contrast-enhanced multislice
      spiral CT (MSCT). 80% of the patients showed peripheral enhancement, and 38% of
      them showed multilocular appearance. deltaCT (The CT on enhanced scan minus that
      on the unenhanced scan) in the central area (15 +/- 12) HU was less than that in
      the peripheral area (27 +/- 16) HU (P < 0.01). The enlarged lymph nodes were
      predominantly distributed in the regions of 4R (87%), 2R (76%), 7 (73%), 10R
      (62%), and 4L (51%). MSCT could reveal the enhancement patterns and predominant
      anatomic distribution, which was of great value for the diagnosis of mediastinal
      tuberculous lymphadenitis.

PMID- 23858749
TI  - [Preliminary study of rabbit experiment modality for evaluating cardiac fatigue].
AB  - This paper presents a preliminary study of rabbit experiment modality
      incorporating a new indicator for evaluating cardiac function changes, providing
      a basis for subsequent study of cardiac fatigue. Using only biochemical
      indicators, such as troponins, is difficult to make a distinction between
      exercise-induced cardiac fatigue (EICF) and exercise-induced cardiac damage
      (EICD). Therefore, some new indicators are needed to evaluate cardiac fatigue
      synthetically. In our study, we used New Zealand white rabbits to conduct a multi
      step swimming experiments with load. We made the rabbits reach an exhaustive
      state to evaluate whether the amplitude ratio of the first to second heart sound
      (S1/S2) and heart rate (HR) during the exhaustive exercise would be decreased and
      whether they would be able to recover after the exhaustive exercise for 24 hours.
      During the first phase of swimming, S1/S2 and HR were increased, and then
      decreased at exhaustive state. They were recovered after the exhaustive exercise
      for 24 hours. Overloading led to deaths of three rabbis, and new phenomena from
      overloading and related to this kind of death were observed. The experiments
      proved that Multi-steps swimming experiments with loads by using New Zealand
      white rabbit is useful for studying cardiac fatigue and premonition of sudden
      cardiac death.

PMID- 23858750
TI  - [Development of a wrist wearing and remote heart rate alarm apparatus].
AB  - We have developed a new wrist wearing heart rate monitoring alarm apparatus,
      which can detect the patients' real-time pulse waves. When the abnormal heart
      rate appears or pulse disappears, the monitoring alarm will sound and dial the
      remote telephone for help simultaneously. This apparatus uses the switch circuit
      to control the keyboard of mobile phone, and dials remote telephone in the help
      of mature technology and communication platform of mobile phones. The intelligent
      program can distinguish digital pulse signal, pick out the correct cycle of
      heartbeat intelligently. The new wrist wearing heart rate monitoring alarm
      apparatus will calculate an average heart rate when it captures consecutively
      five correct electrocardiograph waveforms. It really provides a simple,
      inexpensive and effective way for the patients with heart disease.

PMID- 23858751
TI  - [Continuous ECG recording for freely moving patients].
AB  - As more and more people are becoming aged in China and many of them tend to
      suffer from chronic cardiac problems, the long-term dynamic cardiac monitoring
      for freely moving patients becomes essential. A new design for continuous ECG
      recording on the freely moving patients at home and/or at work is proposed here.
      It is miniature in size, using digital technologies of the low gain amplifier,
      the high resolution analog to digital converter and the real-time digital filter
      that features > 100dB input signal dynamic range (ISDR), > 100dB common-mode
      rejection ratio (CMRR), and < 5microV (RMS) internal noise. The device works
      continuously more than 24 hours with a pair of AAA batteries, and is capable of
      storing the recorded data into a storage card. The preliminary tests showed that
      the P-QRS-T waveforms were captured and displayed smoothly in resting, walking,
      and activities, making the device useful in monitoring and analyzing for the
      patients on the move.

PMID- 23858752
TI  - [The development of the multifunctional automatic rotating bed with process
      monitoring].
AB  - We have developed a new rotating bed for the old and the paralised people. This
      rotating bed is composed of two bed heads at front and at end, bed boards,
      guardrails, an electric motor, a reducer, an induction locator and a set of
      electronic controls. With the preestablished program, the angle between the
      left/right bed board and the middle board is changed by rotating the left/right
      board around the rotation axis, and the gravity direction between the human body
      and the ground is changed by the rotation of the middle board as a whole, so that
      the middle bed board and the left and right ones will act respectively as
      supporters of weight of the person who is lying on his back or on his side. In
      this way, a person can turn over automatically, comfortably and naturally when
      he/she is asleep. This rotating bed meets the physiological needs of a sleeping
      person, and people with turning over problems can turn over in a comfortable and
      natural way by means of biotechnology. It can also improve the quality of sleep
      and help avoid decubitus. In addition, it can be used to promote the
      rehabilitation of those who are paralysed by reason of its passive exercising
      function.

PMID- 23858753
TI  - [Assessment of global left ventricular function in hypertensive patients with
      normal ventricular geometry using global area strain].
AB  - We sought to explore the feasibility of global area strain to assess left
      ventricular global systolic function in patients with essential hypertension and
      normal ventricular geometry. Thirty-five essential hypertensive patients with
      normal ventricular geometry and 30 normally healthy persons as controls were
      enrolled in this study. The two groups were comparable for age, sex ratio,
      height, weight, body mass index (BMI), and heart rate. Blood pressures (BPs) were
      significantly higher in the hypertension group than the control group. Two
      dimensional echocardiography and three-dimensional speckle tracking imaging were
      performed. Left ventricular global area strain (GAS), global longitudinal strain
      (GLS), global circumferential strain (GCS), global radial strain (GRS), LV
      volumes, ejection fraction (EF), sphericity index (SPI), left ventricular end
      diastolic and end-systolic mass (EDmass and ESmass) and LV mass index (EDmassI
      and ESmassI) were obtained. Compared with those of the controls, GAS, GLS, GCS,
      GRS were significantly reduced in hypertensive patients Call P < 0.001). GAS (r =
      0.672, P < 0. 001), GLS (r = 0.587, P < 0.001), GCS (r = 0.639, P < 0.001) and
      GRS (r = 0.685, P < 0.001) were correlated with EF in the pooled population. GAS
      showed an excellent correlation with GCS (r = 0.905, P < 0.001), GLS (r = 0.892,
      P < 0.001) and GRS (r = 0.990, P < 0.001). EF measured with 3D-STI was
      significantly lower in group of hypertension (P < 0.001) than that in the
      controls. There were no significant differences between the two groups in cardiac
      output, sphericity index, EDmass and ESmass, LV mass index (EDmassI and ESmassI)
      calculated with 3D-STI. The study showed that GAS could identify early changes of
      left ventricular global systolic function in hypertensive patients with normal
      ventricular geometry.

PMID- 23858754
TI  - [Numerical simulation of the internal noise in the pressure generator of a
      continuous positive airway pressure ventilator].
AB  - It is important to overcome the problem of noise for the research and development
      of ventilator technologies. Previous research of this subject showed that the
      pressure generator, produced by German EMB-PAPST Company and specially used for
      continuous positive airway pressure (CPAP) ventilator, created noise easily, due
      to local backflow in the volute, uneven velocity distribution in the impeller and
      local negative pressure in the inlet of the impeller. Based on the previous
      research, a combination of the computational fluid dynamics (CFD) software FLUENT
      and steady-state solution of noise source of Reynolds-Averaged Navier-Stokes
      (RANS) was used in this study. We combined equation of Lilley and Synthetic
      Turbulence to get the information about speed fluctuation of the pressure
      generator, which is used to finish noise prediction. After detailed analysis, it
      showed that noise source of different degrees spreaded around the inlet of the
      impeller and the volute, interface of blade edge and corner of the volute tongue,
      which influenced its overall performance to certain extent. Therefore, its
      structural design needs to be improved.

PMID- 23858755
TI  - [Analysis and research on static test methods of elastic modules of biomechanical
      equivalent artificial soft materials].
AB  - This paper is based on the research and analysis of the existing related
      measuring methods, and aimed at the characteristics of equivalent artificial soft
      materials, and it also proposes a new adaptable test method to measure elastic
      modules. The modules are based on capacitive gate transducer and micrometer which
      suits for soft materials. Based on this proposed method, a micro feed mechanism
      has been designed. The same strain of soft materials under compress test was
      realized, and the feasibility of this method by analyzing the test results was
      testified.

PMID- 23858756
TI  - [Development of a testing device for knee joint kinematics parameters of patients
      with strokes].
AB  - This article is aimed to present a design of a testing device for knee joint
      kinematics parameters of patients with strokes. We used Auto CAD to design the
      knee joint sensor device, and applied multifunction data acquisition card to
      collect sensor data. Then we transferred the data to the computer to
      quantitatively detect and analyze the joint angle, angular velocity and other
      parameters. The software system used Visual C+ + MFC frame and shared database
      Access, and used ADO technology to realize the collection between the software
      system and patient information system. After a preliminary test of 20 healthy
      subjects, the result showed that intraclass correlation coefficient (ICC) was
      more than 0.8, indicating a good reliability of the instrument.

PMID- 23858757
TI  - [The preparation and identification of diagnostic recombinant glycerol kinase].
AB  - In order to establish an efficient and low-cost production procedure of
      recombinant glycerol kinase (r-GK), we expressed the r-GK gene at high level in
      E. coli by induction with lactose on a large-scale fermentation of 300L. The
      results showed that the biomass concentration reached OD600 of 42 and the
      expression of r-GK in E. coli accounted for about 30% of total soluble protein.
      The cell-free extract was processed by selective thermo-denaturation and then
      purified with Ni sepharose FF column chromatography. Finally, highly purified r
      GK was obtained and its purity reached 97% by using analysis on sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE), polyacrylamide gel
      electrophoresis (PAGE) and gradient polyacrylamide gel electrophoresis (Gradient
      PAGE). Further identification study showed that the molecular weight of r-GK was
      120kDa with two subunit of 58kDa. Contaminants of NADH oxidase and catalase were
      not detected in the sample pool of r-GK. The purified r-GK was able to retain
      about 85% of its initial activity at 4 degrees C for 30 days. After lyophilized,
      it can retain 93% of its initial activity at 4 degrees C for one year.

PMID- 23858758
TI  - [In vitro evaluation of antibacterial activity and cytocompatibility of
      antibacterial stainless steel containing copper].
AB  - To study the in vitro antibacterial activity and biocompatibility of 317L
      stainless steel containing 4.5% copper alloy (317L-Cu), we produced 317L-Cu
      stainless steel with epsilon-Cu phase. The cell proliferation of osteoblasts on
      material surface was detected in vitro. Escherichia coli was cultured with 317L
      Cu for evaluating the antibacterial activity. We found that the 317L-Cu could
      effectively kill the Escherichia coli on material surface. The cell proliferation
      of osteoblasts on material surface was not different significantly, compared with
      titanium material. Our study clearly demonstrated that the 317L-Cu alloys had a
      significant antimicrobial activity and was biocompatible in vitro, so it would be
      suitable to be used as a new medical material with antibacterial activity.

PMID- 23858759
TI  - [In vitro evaluation of the function of sheet biomaterials in platelet
      activation].
AB  - In China, the evaluation of hemocompatibility of biomaterials is limited to
      hemolysis, coagulation time,and the number and morphology of platelets adhered on
      biomaterials. The present research, however, is aimed to establish a method for
      evaluating the function of sheet biomaterials in platelet activation. Platelet
      activation caused by glass, polyvinyl chloride or polymethylvinylsiloxane sheets
      was evaluated by measuring alpha-granule membrane protein (GMP-140) in platelet
      poor plasma, using a reasonable blood-material contact model vibrating at
      different speed. The result showed that the difference in platelet activation was
      not significantly different among the three above-mentioned materials at 140r/m
      or 200r/m. However, when it comes to 230r/m, significant difference was observed
      among these three groups, with glass > polyvinyl chloride >
      polymethylvinylsiloxane. But the order was reversed at 270r/m, which may be due
      to the different interfacial tension of different materials. Therefore, the
      method is suitable to evaluate platelet activation caused by sheet biomaterials,
      but an appropriate vibrating speed should be chosen. The interfacial tension
      plays an important role in the model and should be considered for results
      assessment.

PMID- 23858760
TI  - [Role of focal adhesion kinase in adhesion and migration of Hep G2 cells].
AB  - Focal adhesion kinase (FAK) plays a critical role in the process of cell adhesion
      and migration by regulating the expression of downstream small G proteins. A kind
      of focal adhesion kinase (FAK) inhibitor was used to inhibit the phosphorylation
      of Y397 site of FAK, and scratch wound migration assay was used to examine the
      effect of FAK inhibitor with different concentrations (0-250 nmol/mL) on the
      migration of hepatomal cells (Hep G2 cells) at 0, 2, 4, 8 and 24h.
      Immunofluorescence analysis and Western blot analysis were performed to detect
      the expression of F-actin and small G proteins Rac1, RhoA and Cdc42 in Hep G2
      cells treated with FAK inhibitor for 120 min. The results indicated that the FAK
      inhibitor can inhibit the migration of Hep G2 cells with a dose- and time
      dependent manner. F-actin was down-regulated in Hep G2 cells treated with FAK
      inhibitor for 120 min, and expression of small G proteins were inhibited at
      different durations. The inhibition of FAK phosphorylation could inhibit cell
      adhesion and migration by down-regulating small G proteins. These results
      suggested that FAK inhibitor can inhibit the migration of tumor cells by blocking
      FAK phosphorylation. This means that FAK inhibitor can block the metastasis of
      tumor cells to surrounding tissues. It may be a potential application in the
      prevention and treatment of cancer.

PMID- 23858761
TI  - [Construction of the lentiviral expression vector for anti-p185(erbB2)
      mouse/human chimeric antibody].
AB  - This research was to construct the lentiviral expression vector for anti-
      p185(erbB2) mouse/human chimeric antibody and to determine the expression of the
      chimeric antibody gene in 293T cells transfected with this vector. The genes (vL
      and vH) coding light and heavy chain of variable regions of anti-p185(erbB2) mAb
      and the constant regions of human IgG1 (kappa and gamma1) were cloned with PCR
      method. The target genes were assembled by three-primers PCR method to obtain the
      chimeric light chain (L) and the chimeric heavy chain (H). Both chains inserted
      into the down stream and upper stream of IRES gene of the plasmid pVAX1/IRES
      respectively. We digested the plasmid pVAX1/ H-IRES-L with endoenzyme and
      subcloned H-IRES-L into the lentiviral vector pWPI. The enzyme digestion and
      sequence analysis showed that the lentiviral expression vector pWPI/H-IRES-L was
      constructed correctly. Then, it was transfected into 293T cells and after 48h,
      GFP protein expression in 293T cells were detected by fluorescent microscope and
      the chimeric antibody expression was detected by RT-PCR and direct ELISA. The
      results showed that after 293T cells were transfected with recombination plasmid,
      both light and heavy chains of the chimeric antibody genes could express
      together. The chimeric antibody expressed could bind to p185(erbB2) specifically.
      This research may lay a sound foundation for further study of anti-p185(erbB2)
      engineered antibody.

PMID- 23858762
TI  - [Correlation analysis between serum free testosterone and total testosterone in
      Chengdu females].
AB  - This paper is aimed to analyze the correlation between serum free testosterone
      (FT) and total testosterone (TT) to acquire a cutoff about using total
      testosterone to diagnose hyperandrogenism in Chengdu females. We investigated
      1854 women by cluster sampling method, detected their serum FT levels and TT
      levels, scored relative items, analyzed the correlation and made the ROC curve to
      get a cutoff of TT levels. Serum FT had a linear correlation with serum TT (r =
      0.597, r2 = 0.356, P < 0.001). The cutoff value was 0.635 ng/mL. The specificity
      and sensitivity were 76.3% and 77.24%, respectively. No correlation found between
      serum FT and Ferriman-Gallway Score (P = 0.392). Positive correlations were seen
      between serum FT and Plewig-Kligman Score (r = 0.137, P < 0.001), serum TT and
      Ferriman-Gallway Score (r = 0.069, P = 0.003) and serum TT and Plewig-Kligman
      Score (r = 0.092, P < 0.001). There is a linear correlation between serum FT and
      TT. We can diagnose hyperandrogenism according to the serum TT cutoff value
      (0.635 ng/mL). Its clinical symptoms are not paralleled with the biochemical test
      results.

PMID- 23858763
TI  - [Construction of microRNA-21 and PTEN eukaryotic expression and short hairpin RNA
      expression vectors].
AB  - The aim of the present study is to construct the recombinant eukaryotic
      expression and short hairpin RNA (shRNA) expression vectors of microRNA-21 and
      phosphatase and tensin homolog deleted on chromosome ten (PTEN). According to the
      gene sequence of microRNA-21 and PTEN, we designed and synthesized two pairs of
      single-stranded siRNA oligonucleotides and PCR primers. After annealing, the
      double-stranded DNA oligonucleotides were cloned into vector Psilencer4. 1-CMV.
      In addition, the gene sequences encoding pre-miR-21 and PTEN were amplified from
      colorectal cancer cell HCT-116 by RT-PCR. Then the PCR products were digested
      with restrictive endonuclease enzyme and cloned into vector pEGFP-N1. The
      constructed recombinant vectors were identified by restrictive digestion and DNA
      sequence analysis. The positive clone was confirmed by double enzyme digestion,
      and the enzyme fragments were consistent with the vector and purpose gene
      sequence. DNA sequencing confirmed that the purpose oligonucleotide fragments
      were correctly inserted in to the eukaryotic expression plasmids. It could be
      concluded that the microRNA-21 and PTEN eukaryotic expression and shRNA
      expression vectors have been successfully constructed, providing a foundation for
      further study on the effect of miR-21 on human colorectal cancer.

PMID- 23858764
TI  - [Measurement and correlation analysis of plasma VEGF level in the patients of
      hyperthyroidism].
AB  - Vascular endothelial growth factor (VEGF) is a glycoprotein that promotes
      endothelial regeneration, stimulates formation of collateral blood vessels and
      increases vascular permeability. The purpose of this study was to measure the
      peripheral blood plasma level of VEGF and FT3, FT4, TSH and to analyze the
      correlation of the level of VEGF and TSH, FT3, FT4, age and gender in the
      patients of hyperthyroidism. The relationship between hyperthyroidism and VEGF
      was investigated as well. The plasma level of VEGF in 45 hyperthyroidism patients
      and 27 healthy persons were measured by enzyme-linked immunosorbent assay
      (ELISA), while plasma FT3, FT4, TSH were detected by chemiluminescence. The
      result showed that the plasma level of VEGF in hyperthyroidism patients [(92.53
      +/- 62.38) pg/mL] was significantly lower than that in the control group [(158.28
      +/- 77.15) pg/mL] (P < 0.01). The plasma level of VEGF correlated with age, and
      that of those over 40Y was significantly higher than that of 40Y or younger (P <
      0.05) in healthy group. Whereas there was no correlation among VEGF, TSH, FT3,
      FT4, age and gender in hyperthyroidism patients (P > 0.05). These results
      suggested that the peripheral blood plasma level of VEGF in hyperthyroidism
      patients was significantly lower than that in the control group. Further
      experimental investigations are needed to estimate the relationship between VEGF
      and hyperthyroidism.

PMID- 23858765
TI  - [Studies of influences of blood glucose controlling on the changes of lipid
      profiles, ApoB100, ApoAI and HDL subclass of newly diagnosed type 2 diabetes].
AB  - This study was aimed to observe if the lipid profiles, apoprotein B100 (ApoB100),
      ApoAI, high density lipoprotein (HDL) and its subclasses could be improved by
      controlling the blood glucose. Fifty-three patients with newly diagnosed type 2
      diabetic were divided into four groups, diet and exercise group (n = 13),
      continuous subcutaneous insulin infusion (CSII) group (n = 14), multiple daily
      insulin injection group (MDI, n = 13), and oral hypoglycaemic agents group (n =
      13). Fasting blood glucose (FPG), glycated hemoglobin A1c (HbA1c), lipid
      profiles, ApoB100, ApoAI and HDL subclasses were measured at beginning and a
      month later. Forty-three patients finished the testing. The levels of FPG, HbA1c,
      triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol
      (LDL-C), and ApoB100 were decreased significantly (P < 0.05) in all groups, and
      ApoAI/ApoB100 increased obviously (P < 0.05). Comparatively matured HDL
      subclasses such as HDL2b were increased (P < 0.05), and comparatively infantile
      HDL subclasses such as HDL3b were decreased (P < 0.05). Therapy with
      hyperglycemic agents improved TG, TC, LDL-C, ApoB100, ApoAI/ApoB100, and HDL2b
      significantly (P < 0.05), but intervention with the diet and exercise group alone
      did not improve lipid profiles, apolipoproteins, and HDL subclasses (P > 0.05).
      Meanwhile, therapy with insulin intensive therapy (MDI, CSII) group had the most
      powerful effect on decreasing ApoB100 concentration (P < 0.05). The results
      suggested that lipid profiles, apolipoproteins, and quantity and quality of HDL
      subclasses might be improved by blood glucose controlling.

PMID- 23858766
TI  - [Research and analysis of failure data of contemporary artificial joint
      registration system].
AB  - This paper is aimed to focus on the joint prosthesis failure event, to collect
      the statistic data about the failure of artificial joints issued by authoritative
      organizations at home and aboard, and to compare the functions of different types
      of the artificial joints. We generalized and compared current study analyzing the
      failure reason and type of joint prosthesis, and categorized the failure events
      according to the failure occurring time, i. e. short-term, medium-term and long
      term. This paper could be helpful for improving and summarizing of artificial
      joint replacement surgery, and could put forward the requirements for the future
      artificial joints.

PMID- 23858767
TI  - [An automatic inspection technology for angiostenosis in contrastographic image].
AB  - This paper presents an automatic calculation method for angiography image, which
      enables programs to intellectively acquire several parameters of blood vessels,
      such as contours, segments, widths, etc. and then intellectively identify the
      angiostenosis parts. This method is a kind of automatic optic inspection (AOI)
      technology. Blood vessels usually distribute as curves and have a fastening
      direction. According to this feature, the approach performs inspection
      automatically using improved Steger algorithm, which firstly computes the
      convolution between image and Gaussian function kernel, and then computes second
      order Taylor expansion at eac pixel. And further the eigenvalues and eigenvectors
      of Hessian matrix are calculated on each pixel to obtain the direction of lines
      and local maximum of second derivative at that point. Hysteresis threshold and
      directional connection operators are then used to generate blood vessel skeleton.
      Finally we can compute the blood vessel widths for every sub-pixel object points
      on blood vessel curve. For given digital X-ray images of hearts with blood vessel
      local straitness, experiments showed that this method had the ability of getting
      all the data we need and could find the local confined parts in blood vessels.
      This approach is proved to have a good effort for angiography images, and it has
      some advantages such as fast speed, high accuracy, good robustness and no need
      for human interventions. It could also be a promising computer aided diagnosis
      method.

PMID- 23858768
TI  - [An FES system based on dual axis inclinometer in foot drop treatment].
AB  - The foot drop functional electrical stimulation (FES) system consisting of
      various sensors has been widely applied to the disease of the foot drop. However,
      the current system is limited to the research on walking on the ground and
      ignores other important actions of foot in one's daily life, such as walking up
      and down the stairs, squatting and lying down, etc. In this work, we applied the
      dual axis angle sensor to the system of the foot drop FES for the first time.
      Such a system can not only stimulate the foot drop during normal walking, but
      also identify squatting, sitting, and lying down etc. and furthermore, the system
      can switch off automatically. In the meanwhile, it can also detect falls and
      other dangerous actions. The accuracy of our system can achieve 100%, 81.9%,
      95.8%, 99.0% and 66.9% for normal walking, sitting-standing, walking up the
      stairs, walking down the stairs and squatting-standing respectively.

PMID- 23858769
TI  - [Comprehensive testing system for cardiorespiratory interaction research].
AB  - To investigate the modulation effects of breathing movement on cardiovascular
      system and to study the physiological coupling relationship between respiration
      and cardiovascular system, we designed a comprehensive testing system for
      cardiorespiratory interaction research. This system, comprising three parts, i.
      e. physiological signal conditioning unit, data acquisition and USB medical
      isolation unit, and a PC based program, can acquire multiple physiological data
      such as respiratory flow, rib cage and abdomen movement, electrocardiograph,
      artery pulse wave, cardiac sounds, skin temperature, and electromyography
      simultaneously under certain experimental protocols. Furthermore this system can
      be used in research on short-term cardiovascular variability by paced breathing.
      Preliminary experiments showed that this system could accurately record rib cage
      and abdomen movement under very low breathing rate, using respiratory inductive
      plethysmography to acquire respiration signal in direct-current coupling mode.
      After calibration, this system can be used to estimate ventilation non
      intrusively and correctly. The PC based program can generate audio and visual
      biofeedback signal, and guide the volunteers to perform a slow and regular
      breathing. An experiment on healthy volunteers showed that this system was able
      to guide the volunteers to do slow breathing effectively and simultaneously
      record multiple physiological data during the experiments. Signal processing
      techniques were used for off-line data analysis, such as non-invasive ventilation
      calibration, QRS complex wave detection, and respiratory sinus arrhythmia and
      pulse wave transit time calculation. The experiment result showed that the
      modulation effect on RR interval, respiratory sinus arrhythmia (RSA), pulse wave
      transit time (PWTT) by respiration would get stronger with the going of the slow
      and regular breathing.

PMID- 23858770
TI  - [Content-based automatic retinal image recognition and retrieval system].
AB  - This paper is aimed to fulfill a prototype system used to classify and retrieve
      retinal image automatically. With the content-based image retrieval (CBIR)
      technology, a method to represent the retinal characteristics mixing the fundus
      image color (gray) histogram with bright, dark region features and other local
      comprehensive information was proposed. The method uses kernel principal
      component analysis (KPCA) to further extract nonlinear features and
      dimensionality reduced. It also puts forward a measurement method using support
      vector machine (SVM) on KPCA weighted distance in similarity measure aspect.
      Testing 300 samples with this prototype system randomly, we obtained the total
      image number of wrong retrieved 32, and the retrieval rate 89.33%. It showed that
      the identification rate of the system for retinal image was high.

PMID- 23858771
TI  - [Numerical simulation on cycle change form of the pressure and wall shear in
      human upper respiratory tract].
AB  - The research on cycle change form of the pressure and the wall shear in human
      upper respiratory tract can strengthen understanding of the characteristics of
      the airflow in the place and provide us with a scientific basis for analyzing the
      diffusion, transition and deposition patterns of aerosol there. In our study, we
      used large eddy simulation to emulate the pressure and wall shear in human upper
      respiratory tract in conditions of the low intensive respiratory patterns, and
      discussed the distributing disciplinarian of the pressure and wall shear in mouth
      throat model and trachea-triple bifurcation. The results showed that the pressure
      gradient variation in human upper respiratory tract was mainly fastened from root
      of epiglottis to trachea. The minimum pressure at the interim of inspiration was
      a duplication of the interim of expiration, and located on the posterior wall of
      the glottis. The pressure gradient variation was evident on trachea and its fork.
      The wall shear changed with the velocity of the air flow, and its direction
      changed periodically with breath cycle.

PMID- 23858772
TI  - [Effect of zinc ion on polymerization and cytotoxicity of sTRAIL in tumor cells].
AB  - Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is
      potentially a novel anti-cancer drug due to its superior selective cytotoxicity
      in a wide variety of tumor cells. Zinc ion (Zn2+) insufficiency might be an
      important cause for weak cytotoxicity of sTRAIL prepared by gene engineering. In
      this paper, the sTRAIL protein is highly-expressed with insertion of the
      synthesized gene encoding sTRAIL into pQE30 plasmid. The polymerization and
      cytotoxicity in tumor cells of sTRAIL prepared in presence of different
      concentrations of Zinc ions were compared. It was found that the sTRAIL protein
      prepared in absence of Zinc ions mainly existed as monomer with weak
      cytotoxicity. However, in the presence of Zinc ions, sTRAIL formed homotrimer and
      showed strong cytotoxicity in tumor cells. These results demonstrate that Zinc
      ion is very important for cytotoxicity of sTRAIL. It is necessary for keeping
      stable activity of sTRAIL by addition of proper concentration of Zinc ion in the
      media.

PMID- 23858773
TI  - [Effects of chain length of polyacrylic acid (PAA) on proteins adsorption of
      polystyrene-polyacrylic acid (PS-PAA) spherical polyelectrolyte brushes].
AB  - We studied the interaction between proteins and polystyrene-polyacrylic acid (PS
      PAA) spherical polyelectrolyte brushes with different polyacrylic acid (PAA)
      chain lengths, including the physical adsorption and chemical adsorption in PBS
      buffer. Results showed that the amount of bovine serum albumin (BSA) physically
      adsorbed on PS-PAA spherical polyelectrolyte brushes decreased to a minimum of 33
      microg/mg whereas the amount of streptavidin (SA) chemically adsorbed increased
      with the increase of chain length and carboxyl quantity. The biotin binding
      capacity of streptavidin chemically adsorbed on PS-PAA spherical polyelectrolyte
      brushes was roughly evaluated via enzyme competitive inhibition.

PMID- 23858774
TI  - [Current progress in research on the nanomaterials for biological macromolecules
      recognition].
AB  - The combination of nanotechnology and molecular imprinting technique, including
      their application research in biomedical domain, provides a new solution to the
      problem of the substitutes for antibodies, enzymes, and other native biological
      structures as well as cell bracket materials. Nanocavity biomaterials with
      recognition specificity imprinted by using proteins as templates have numerous
      applications in biotechnology, medicine and so on. This review presents the
      aspects of molecular imprinting nanostructure involved in the biomacromolecules
      imprinting, and it explores the precent developments and achievements of
      nanomaterials for molecular imprinting technology.

PMID- 23858775
TI  - [Research on tissue engineered cartilage for repairing of articular cartilage
      damage and defects].
AB  - Articular cartilage damage is very common in clinical practices. Due to the low
      self healing abilities of articular cartilage, it must be repaired or substituted
      by implants once natural articular cartilage is damaged. On the other hand, the
      various technologies currently used for healing damaged articular cartilage are
      little satisfactory, and rarely restore full function or return the tissue to its
      natively normal state. Tissue engineering technology holds great promise for the
      healing of damage or defects of articular cartilage. Tissue engineered articular
      cartilage is one of the most promising methods for repairing articular cartilage
      trauma and defects. In this paper, the authors review the research progress of
      three elements such as seed cells, growth factors and scaffolds which constitute
      tissue engineered articular cartilage.

PMID- 23858776
TI  - [Advances of researches on caspases in neurodegenerative diseases].
AB  - Acute and chronic neurodegenerative diseases are illnesses associated with high
      morbidity and mortality, and few or no effective options are available for their
      treatments. Many neurodegenerative diseases are included in them, for example,
      stroke, brain trauma, spinal cord injury, amyotrophic lateral sclerosis (ALS),
      Huntington's disease, Alzheimer's disease, and Parkinson's disease. Given that
      central nervous system tissue has very limited, if any, regenerative capacity, it
      is of utmost importance to limit the damage caused by neuronal death. During the
      past decade, considerable progress has been made in understanding the process of
      cell death. In this article, we review the causes and mechanisms of neuronal-cell
      death, especially as it pertains to the caspases family of proteases associated
      with cell death. The results may be helpful to the experimental research and
      clinical application of neurodegenerative diseases.

PMID- 23858777
TI  - [Research progress in sperm mediated gene transfer technology].
AB  - With the rapid development of biotechnology, we can change the trait of organism
      using transgenetic technology. In recent years, there are growing interests in
      the establishment of sperm mediated gene transfer (SMGT) technology as an
      effective and convenient method to produce transgenic animals. SMGT technology is
      a transgenetic method, which is easy in operation and does little harm to the
      cell compared with the other transgenetic methods. In this review, we expound the
      background, development, mechanism, operation and application of SMGT.

PMID- 23858778
TI  - [Research progress of computational models of affecting factors for ventricular
      diastolic function].
AB  - There have been insufficient numerical methods for particular description and
      quantitative evaluation of left ventricular diastolic function in the studies in
      this area. We therefore have summarized the computational models of the affecting
      factors for diastolic function from five aspects, i. e. the geometry shape of
      left ventricular, myocardial stiffness, myocardial viscosity, myocardial
      relaxation and ventricular interaction respectively. Controlling the sensitive
      parameters and having a mathematical description on left ventricular diastolic
      dysfunction can provide numerical methods for clinical diagnosis and quantitative
      evaluation of the disease.

PMID- 23858779
TI  - [Recent advance in tendon tissue engineering using scaffolding biomaterials].
AB  - An ideal biologically derived that tissue engineering material of tendon has
      biological activities and functions, so that it may lead to a perfect effect in
      histological reparation and reconstruction. In addition, the tissue engineering
      material can avoid disease transmission, be provided from variety of sources and
      be weak in immune responses. Generally, there are two kinds biologically derived
      material, i. e. natural biomaterials and purified biomaterials. In this review,
      researches about the effect, capability and relevant preparation methods,
      enhancing strategies and the development in the future are discussed.

PMID- 23858780
TI  - Foreword. Yusho, oil disease.

PMID- 23858781
TI  - [Antibodies to specific nuclear antigens in patients with Yusho].
AB  - To investigate chronic immune effects of polychlorinated biphenyl (PCB) and
      polychlorinated dibenzofuran (PCDF), autoantibodies including anti-Smith (Sm)
      antibody, anti-ribonucleoprotein (RNP) antibody, anti-centromere antibody and
      anti-double-stranded DNA (dsDNA) antibody, were studied in 168 patients with
      Yusho and 54 controls in 2012. Autoatibodies were present in some patients of
      Yusho; 1 case (0.6%) for anti-Sm antibody, 4 cases (2.4%) for anti-centromere
      antibody and 11 cases (6.5%) for anti-dsDNA antibody. However, these
      autoantibodies were not demonstrated in any controls. There was a significantly
      higher prevalence of elevated anti-centromere antibody in subjects with high PCB
      concentration than in those with low PCB concentration. We conclude that anti
      centromere antibody is present in patients with Yusho, and it may be associated
      with blood PCB concentration.

PMID- 23858782
TI  - [Relationships between concentrations of dioxin isomers and symptoms, and among
      concentrations and half-lives of dioxin isomers, in patients with Yusho disease].
AB  - The relationships among dioxin isomers are not well understood. This study aimed
      to clarify the relationships among isomers using two methods. First, the
      relationships between isomers and symptoms were analyzed by analysis of variance.
      Second, concentrations and half-lives were determined for each isomer in each
      patient, and correlation coefficients for the concentrations and half-lives among
      isomers were calculated. Two isomers very similar to 2, 3, 4, 7, 8
      pentachlorodibenzofuran (2, 3, 4, 7, 8-PeCDF) were correlated with symptoms of
      Yusho disease. The correlation coefficients among three isomers similar to 2, 3,
      4, 7, 8-PeCDF were very high at 0.98, indicating that there may be a mechanism
      which maintains constant ratios among these isomers.

PMID- 23858783
TI  - [Adipokine profile of Yusho patients].
AB  - Serum levels of adipokines among Yusho patients and normal controls were
      measured. Compared with normal controls, serum levels of leptin were
      significantly lower, while those of RBP4 were significantly higher in Yusho
      patients. Dioxins may impair production of adipokines from adipose tissue, which
      would increase the risk to develop lifestyle-related diseases, such as diabetes
      mellitus and hypertension.

PMID- 23858784
TI  - [Serum levels of IL-21 and TGF-beta in the Yusho patients].
AB  - Aryl hydrocarbon receptor (AhR), recognized as a dioxin receptor, is expressed on
      the surface of helper T (Th) 17 cells. As PCBs and PCDFs are still detected in
      the sera of the Yusho patients, we hypothesized dysregulation of Th17 cells in
      the Yusho patients. In the present study, we measured IL-21 and TGF-beta in the
      Yusho patients which induce differentiation from Th0 to Th17 cells. Serum levels
      of IL-21 were lower than those of controls (p < 0.05). Meanwhile, serum levels of
      TGF-beta were decreased relative to controls, but not significant. These results
      may imply differentiation from Th0 cells to Th17 cells is not induced in the
      Yusho patients.

PMID- 23858785
TI  - [Serum levels of IL-10 and IL-35 in Yusho patients].
AB  - We thought that dioxin and dioxin-like compound receptor AhR expressed on the
      surface of regulatory T (Treg) cells and Th17 cells could regulate immunological
      functions in the Yusho patients. In the present study, we measured Treg cell
      related cytokines IL-10 and IL-35 in the Yusho patients. Serum levels of IL-10
      were higher, but not significant (p = 0.06), and serum levels of IL-35 were
      increased (p = 0.006) in comparison with healthy controls. These results imply
      Treg cell activation in the Yusho patients.

PMID- 23858786
TI  - [Increased rate of serum uric acid levels in Yusho sufferers].
AB  - We measured serum uric acid levels in Yusho sufferers annually from 2007 to 2012
      in Nagasaki prefecture. We observed an increased rate of serum uric acid levels
      in 38.2% of the male and 5.5% of the female sufferers. There was no relation
      among serum uric acid value, Body Mass Index, liver function, blood
      polychlorinated biphenyls and hypersensitive C reactive protein. We conclude that
      it is unclear if blood polychlorinated biphenyls may play a role in the increase
      of serum uric acid levels in Yusho sufferers.

PMID- 23858787
TI  - [A clinical study of TMJ arthrosis in Yusho patients].
AB  - In the present study, we clarified the TMJ symptoms of Yusho patients. An
      epidemiologic examination was carried out to identify TMJ arthrosis in patients
      with Yusho. The patients were collected during annual Yusho examinations in 2012.
      Nine of 187 patients had TMJ symptoms. The symptoms were pain, trismus, and a
      clicking sound of the TMJ. We diagnosed these patients with TMJ arthrosis. The
      rate of TMJ arthrosis in Yusho patients was 4.8%, being similar to the rate of
      TMJ arthrosis in general. The PCB concentration in the blood of these 9 patients
      was 2.76 ppb, and the average blood PCB concentration of all patients was 2.98
      ppb. We identified no relationship between the blood PCB concentration and TMJ
      arthrosis.

PMID- 23858788
TI  - [Inter-laboratory crosscheck study of dioxins and PCBs in human blood samples].
AB  - We developed an analytical method for accurately determining the concentrations
      of dioxin and polychlorinated biphenyls(PCBs) in a blood volume of 5 g. Inter
      laboratory crosscheck is available for maintaining the quality of dioxin and PCB
      analysis. We carried out the crosschecks of dioxin and PCB analysis in the blood
      with domestic analysis organizations. Two crosschecks each of dioxin and PCB
      analysis were carried out from 2007 through 2011. As a result, the findings of
      our analysis accorded well with the analyses of the other organizations. We
      believe that our analytical method is sufficiently reliable.

PMID- 23858789
TI  - Development of a newly large-volume injection system for dioxin determinations in
      blood of Yusho patients.
AB  - We developed a more effective method to measure the concentrations of
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      and non-ortho-coplanar polychlorinated biphenyls (non-ortho PCBs) in the blood of
      Yusho patients using high-resolution gas chromatography/high-resolution mass
      spectrometry (HRGC/HRMS) equipped with a newly large-volume injection system. The
      new injection system linked a LaviStoma system with a unique stomach-shaped inlet
      liner (SSIL) and a solvent-cut large-volume (SCLV) injection system. This
      approach made it possible to introduce volumes up to 200 microl into the
      HRGC/HRMS in comparison with the 20microl volume of the previously reported
      conventional SCLV method. Based on experiments conducted using the same blood
      sample, the concentrations of PCDDs, PCDFs, and non-ortho PCBs obtained by the
      developed method showed a close correlation to that by the conventional SCLV
      method. By improving the injection method, the operation time and labor for the
      purification procedure from blood could be reduced. Furthermore, the developed
      method was more effective than the conventional SCLV method for recovery of
      PCDDs, PCDFs, and non-ortho PCBs.

PMID- 23858790
TI  - The changes in dioxin concentrations in the blood of Yusho patients from 2004 to
      2010.
AB  - We measured the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in
      blood collected from Yusho patients during medical health examinations performed
      from 2004 to 2010. Out of the 242 and 200 Yusho patients who received medical
      health examinations in 2004 and 2010, respectively, the concentrations of PCDDs,
      PCDFs, and PCBs in the blood of 136 patients were measured in both of those
      years. The concentrations of individual congeners of PCDDs, PCDFs, and PCBs in
      the blood of these 136 Yusho patients measured in 2004 were compared with those
      measured in 2010. Among individual congeners of PCDDs, PCDFs, and PCBs, most
      congeners of these compounds did not significantly decrease from 2004 to 2010.
      However, the concentrations of 1, 2, 3, 4, 6, 7, 8-heptaCDD, octaCDD, 1, 2, 3, 4,
      7, 8-hexaCDF, tetraCB 52/69, pentaCB 101, octaCB 198/201, and octaCB 196/203 in
      the blood of Yusho patients were significantly decreased from 2004 to 2010. In
      addition, the concentrations of 1, 2, 3, 6, 7, 8-hexaCDD, 2, 3, 4, 7, 8-pentaCDF,
      and 1, 2, 3, 6, 7, 8-hexaCDF tended to decrease slightly from 2004 to 2010. These
      findings suggest that the PCDDs, PCDFs, and PCBs have remained in the blood of
      Yusho patients for a very long time, with over 40 years having passed since the
      outbreak of Yusho.

PMID- 23858791
TI  - Improvement of measurement method for hydroxylated polychlorinated biphenyls (OH
      PCBs) in blood samples using LC/MS/MS.
AB  - Hydroxylated polychlorinated biphenyls (OH-PCBs) are well known as metabolites of
      PCBs in the human body. We improved a measurement method for OH-PCBs in blood
      samples using LC/MS/MS. A new 2 microm particle column was used, and the
      analytical conditions for the LC/MS/MS measurements were optimized. The improved
      method is more sensitive than the conventional method for 5g blood samples. And,
      this method is effective at determining the concentrations of OH-PCBs, PCBs and
      dioxins from the same sample without special treatment of the sample such as
      derivatization.

PMID- 23858792
TI  - Concentration of hydroxylated polychlorinated biphenyls (OH-PCBs) in the blood of
      Yusho patients in 2010.
AB  - Hydroxylated polychlorinated biphenyls (OH-PCBs) are formed as major metabolites
      of PCBs by cytochrome P450 enzyme-mediated oxidation. It has been reported that
      their total concentration in serum samples of Yusho patients ranged from 390 to
      1300 pg/g. We measured the concentration of OH-PCBs in blood collected from 183
      Yusho patients living in Japan in 2010. The major OH-PCB metabolites were 4-OH
      CB187 (ND-1300 pg/g-wet), 4-OH-CB146 + 3-OH-CB153 (8.4-1200 pg/g-wet), 4-OH-CB109
      (ND-530 pg/g-wet) and 4'-OH-CB172 (ND-380 pg/g-wet). The total OH-PCBs ranged
      from 36 to 3800 pg/g-wet. A positive relationship between the concentrations of
      OH-PCBs and PCBs was observed, but no significant relationship between the
      concentrations of OH-PCBs and PCDD/DFs was observed.

PMID- 23858793
TI  - [The gender-specific effect of maternal exposure to dioxin on fetal
      steroidogenesis in the adrenal gland].
AB  - Maternal exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) causes a
      number of toxic effects on development such as growth retardation and sexual
      immaturity in the offspring. However, the toxic mechanism remains unknown. Our
      previous studies have revealed that single oral administration of TCDD (1 jg/kg)
      to pregnant rats at gestational day (GD) 15 attenuates the fetal expression of
      testicular steroidogenic proteins such as steroidogenic acute-regulatory protein
      (StAR) and cytochrome P450 (CYP) 17 by targeting the fetal production of
      pituitary gonadotropins. In addition, we provided evidence that TCDD-produced
      damage on the fetal pituitary-gonad axis leads to imprint defects in sexual
      behaviors at adulthood. In this study, we investigated whether TCDD also affects
      fetal steroidogenesis in the adrenal gland. When pregnant Wistar rats were orally
      treated with TCDD, the fetal expression of CYP21, CYP11B1 and CYP11B2 mRNAs was
      either induced or tended to be induced in the male adrenal gland during GD17 and
      GD19, while the expression of mRNAs coding for StAR, CYP11A1 and 313
      hydroxysteroid dehydrogenase was insensitive to TCDD treatment. The above
      alterations did not seem to be caused through a change in the upstream regulator,
      because TCDD exhibited little ability to attenuate the expression of
      adrenocorticotropin, a pituitary hormone stimulating adrenal steroidogenesis, in
      the male and female fetuses. In contrast to the males, TCDD effect on the adrenal
      gland was not observed in the female fetuses. These results suggest that maternal
      exposure to TCDD disrupts fetal steroidogenesis in adrenal as well as gonadal
      glands in a male specific manner, and the mechanism underlying the effect on
      adrenal gland is independent of the alteration of pituitary regulator.

PMID- 23858794
TI  - [Examination of alkali digestion temperature in isomer specific analysis of PCB
      in whole blood sample].
AB  - We compared concentrations of PCB congeners between conventional 80 degrees C
      alkali digestion method and 30 degrees C alkali digestion method using 22
      individual blood samples collected during 2009 annual Yusho examinations. The
      mean concentration of tri-CB in 30 degrees C alkali digestion method was lower
      than that of conventional method. However, concentration of total PCBs,
      2,3',4,4',5-pentaCB (PCB118), 2,2',4,4',5,5'-hexaCB (PCB153) and 2,3,3',4,4', 5
      hexaCB (PCB156), which were used as index for Yusho diagnosis, were equivalent
      between the methods. It was considered that the 30 degrees C alkali digestion
      method was available for blood PCB congener specific analysis in Yusho diagnosis.

PMID- 23858795
TI  - [Species difference in the metabolism of 2, 2', 3, 4', 5, 5'-hexachlorobiphenyl
      (CB146) by animal and human liver microsomes].
AB  - The in vitro metabolism of 2, 2', 3, 4', 5, 5'-hexachlorobiphenyl (hexaCB)
      (CB146) was examined using liver microsomes of rats, guinea pigs, hamsters and
      human. Untreated animal livers produced one metabolite (M-2) in rats, three
      metabolites (M-l, M-2and M-3) in guinea pigs and no metabolite in hamsters.
      Pretreatment of phenobarbital (PB) resulted in a marked increase of M-1 in three
      animals and of M-2in guinea pigs. In contrast, pretreatment of 3
      methylcholanthrene showed a significant increase of M-3 in guinea pigs and a
      decrease of M-2in rats. Human liver microsomes prepared from nine Caucasians
      mainly formed M-2and M-3 at a ratio of 2: 1 and two individuals also formed one
      more metabolite M-1. The formation of M-1 was significantly correlated with
      CYP2B6 activity. By comparison of the GC-MS data of three metabolites with
      synthesized authentic samples, M-1 and M-2were determined to be 3'-hydroxy (OH)
      CB146 and 4-OH-CB146, respectively. However, M-3 is unclear at present except the
      fact that it is OH-hexaCB. These results suggest that 3'-OH-CB146 is formed by PB
      inducible cytochrome P450 (CYP2B enzymes) in animal and human livers and 4-OH
      CB146 is a major metabolite in rat and human liver.

PMID- 23858796
TI  - [Outcome of visual acuity after surgical removal of pituitary adenomas].
AB  - INTRODUCTION: Pituitary adenomas with suprasellar extension may produce anterior
      visual pathway compression, resulting in characteristic visual deficit. Surgical
      decompression of these structures prevents further visual deterioration and its
      postoperative recovery. OBJECTIVE: The aim of this study was to investigate pre-
      and postoperative visual acuity (VA) in patients with pituitary adenomas, and to
      detect the influence of prognostic factors, such as symptoms duration, degree of
      visual acuity reduction and tumor size in the assessment of the prognosis of
      postoperative visual function. METHODS: We analyzed 40 consecutive patients who
      fulfilled three criteria: evidence of preoperative visual dysfunction,
      transsphenoidal ortransfrontal tumor resection and hystologically verified
      pituitary adenoma. A visual examination was performed under standard conditions,
      pre and postoperatively (10 days, one month and six months after surgery). A
      paired t-test was used to assess the differences of pre- and postoperative
      characteristics values, and the Chi-square test of independence in the assessment
      of the influence of prognostic factors. RESULTS: Postoperative improvement of VA
      was seen in 84.61% patients (68% eyes). Eyes with preoperative mild and moderate
      degree of VA reduction showed improvement in 89.65% eyes in contrast to 22.60%
      eyes with preoperative severe reduction of VA, which was all statistically
      significant. Eyes in patients with tumor smaller than 20 mm had improvement of VA
      in 91.66% eyes, while eyes with tumor larger than 40 mm had improvement of VA in
      61.11% eyes, which was statistically significant. When symptoms duration was
      below two years the improvement of VA was detected in 65.38% eyes as related to
      50% eyes with symptoms duration exceeding two years, which was not statistically
      significant. CONCLUSION: Pituitary adenomas commonly cause visual impairment.
      Postoperatively the majority of patients show a distinct improvement of visual
      acuity. The degree of preoperative visual loss and tumor size influence the final
      visual outcome, and not the duration of symptoms.

PMID- 23858797
TI  - Analysis of polymorphism in the survivin gene promoter as a potential risk factor
      for head and neck cancers development.
AB  - INTRODUCTION: Association studies have shown that gene polymorphisms in various
      classes of genes can modulate cancer risk. The -31G/C polymorphism in the
      promoter of survivin gene, affects the expression of the anti-apoptotic protein
      survivin which in turn may predispose an individual to some types of cancer.
      OBJECTIVE: The aim of the study was to determine whether the survivin promoter 
      31G/C polymorphism could be a susceptibility factor for squamous cell carcinoma
      (SCC) of the oral cavity and basal cell carcinoma (BCC) of the skin. METHODS: The
      DNA obtained from 88 patients with SCC, 60 patients with BCC and 111 healthy
      individuals was subjected to polymerase chain reaction-restriction fragment
      length polymorphism analysis (PCR-RFLP) in order to determine genotype and allele
      frequencies in patients and control groups. Logistic regression was used for
      cancer risk assessment. RESULTS: The following distribution of genotypes was
      obtained: CC genotype 15% in the SCC group, 13% in the BCC group and 12% in
      controls; CG genotype 41% in SCCs, 35% in BCCs, 48% in controls; GG genotype 44%
      in SCCs, 52% in BCCs and 40% in controls. Allelic frequencies were as follows: G
      allele 0.65 in SCCs, 0.69 in BCCs and 0.64 in the control group; C allele 0.35 in
      SCCs, 0.31 in BCCs and 0.36 in the control group. There was no statistically
      significant difference in allele or genotype frequencies between the patients and
      controls (p>0.05). CONCLUSION: In Serbian population, -31G/C polymorphism in the
      promoter of the survivin gene cannot be considered as a risk factor for oral
      squamous cell carcinoma and skin basal cell carcinoma.

PMID- 23858798
TI  - Virtual histology study of atherosclerotic plaque composition in patients with
      stable angina and acute phase of acute coronary syndromes without ST segment
      elevation.
AB  - INTRODUCTION: Rupture of vulnerable atherosclerotic plaques is the cause of most
      acute coronary syndromes (ACS). Postmortem studies which compared stable coronary
      lesions and atherosclerotic plaques in patients who have died because of ACS
      indicated high lipid-core content as one of the major determinants of plaque
      vulnerability. OBJECTIVE: Our primary goal was to assess the potential relations
      of plaque composition determined by IVUS-VH (Intravascular Ultrasound -Virtual
      Histology) in patients with stable angina and subjects in acute phase of ACS
      without ST segment elevation. METHODS: The study comprised of 40 patients who
      underwent preintervention IVUS examination.Tissue maps were reconstructed from
      radio frequency data using IVUS-VH software. RESULTS: We analyzed 53 lesions in
      40 patients. Stable angina was diagnosed in 24 patients (29 lesions), while acute
      phase of ACS without ST elevation was diagnosed in 16 patients (24 lesions). In
      the patients in acute phase of ACS without ST segment elevation IVUS-VH
      examination showed a significantly larger area of the necrotic core at the site
      of minimal lumen area and a larger mean of the necrotic core volume in the entire
      lesion comparing to stable angina subjects (1.84+/-0.90 mm2 vs. 0.96+/-0.69 mm2;
      p<0.001 and 20.94+/-15.79 mm3 vs. 11.54+/-14.15 mm3; p<0.05 respectively).
      CONCLUSION: IVUS-VH detected that the necrotic core was significantly larger in
      atherosclerotic lesions in patients in acute phase of ACS without ST elevation
      comparing to the stable angina subjects and that it could be considered as a
      marker of plaque vulnerability.

PMID- 23858799
TI  - The effect of metabolic and hormonal parameters on microalbuminuria in
      adolescents with type 1 diabetes mellitus.
AB  - INTRODUCTION: The prevalence of microalbuminuria (MA), the most important early
      marker of incipient nephropathy in patients with type 1 diabetes mellitus (T1DM),
      increases during puberty, the period of exaggerated physiological insulin
      resistance. OBJECTIVE: To assess the prevalence of MA and the relationship
      between MA and metabolic risk factors and pubertal hormones in adolescents with
      T1DM. METHODS: In a cross-section study involving a group of 100 adolescents of
      both sexes of mean age 14.90+/-2.18 years and with mean duration ofT1DM 5.99+/
      73.64 years, we assessed the presence of MA. In all patients, we determined
      albumin-to-creatinine ratio (ACR) in two or three morning first-void urine
      samples in the period up to 6 months. Persistent MA was confirmed in the patients
      with the finding of ACR rating 2.5-25 mg/mmol in males and 3.5-25 mg/mmol in
      females in two out of three first morning urine samples. RESULTS: MA developed in
      16 (16.0%) patients. Predictors of MA determined by using multiple logistic
      regression were high HbA1c (OR 4.6; 95% CI 2.1-10.0), higher night-time SBP (OR
      1.9; 95% CI 0.8-1.3) and higher insulin dose (OR 62.6; 95% CI 2.3-1678.5).
      Markers of insulin resistance such as higher body mass index (BMI) which was
      statistically significantly related to MA (p= 0.241, p<0.05) and higher
      dehydroepiandrosterone sulfate (DHEA-S) which was significantly higher in
      patients with MA (7.82 micromol/L vs. 5.02 micromol/L, p<0.01), were also
      identified as predictors but did not remain significant by multivariate analysis,
      possibly because of a small sample of subjects with persistent MA. CONCLUSION: In
      addition to poor glycemic control and higher night-time systolic blood pressure,
      markers of insulin resistance (higher insulin dose, higher BMI and higher DHEA-S)
      contribute to the increased risk of MA.

PMID- 23858800
TI  - [Extrahepatic manifestations of chronic hepatitis C and their influence on
      response to treatment with pegylated interferon alfa-2a and ribavirin].
AB  - INTRODUCTION: Thirty to 50% of patients with chronic hepatitis C (CHC) have one
      or more extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection.
      OBJECTIVE: The aim of this study was to evaluate the frequency of EHMs and to
      investigate the efficacy of pegylated interferon (Peg-IFN)-alpha-2a plus
      ribavirin therapy in patients with HCV-related EHMs. METHODS: The study included
      280 patients suffering from CHC and treated with Peg-IFN-alpha-2a and
      ribavirin.The patients were divided in two groups according to presence or
      absence of EHMs. We evaluated virological response to antiviral therapy. RESULTS:
      One or more EHMs were found among 27.9% of patients. Most frequently they had
      rheumatoid factor in serum (12.5%), organ-nonspecific antibodies ANA and AGMA
      (12.4%), thyroid hormone disorders (9.3%), vasculitis (5.7%), diabetes mellitus
      (4.65%), glomerulonephritis (0.71%), and porphyria cutanea tarda (0.36%). Among
      the patients with EHMs there was 52.6% of females vs. 30.2% of females in the
      group of patients without EHMs (p=0.001). HCV genotypes 1 and 4 had 85.9%
      patients with EHMs vs. 58.4% of patients without EHMs (p=0.000). Progressive
      fibrosis and cirrhosis were more frequently recorded in the EHM group of patients
      (32% vs. 23.2%), but without statistically significant difference (p=0.532).
      Serious adverse events of Peg-IFN-alpha-2a and ribavirin were statistically
      significantly recorded among the patients with EHMs (46.1% vs. 12.9%; p=0.000).
      Sustained virological response among the patients with and without EHMs rated
      56.9% and 70.8% respectively (p=0.125). CONCLUSION: Patients with CHC and EHMs
      treated with combined Peg-IFN-alpha-2a and ribavirin experience handling
      difficulties, more often have serious adverse events, while successful outcome is
      achieved in about 50% of patients.

PMID- 23858801
TI  - Significance of the application of oral rehydration solution to maintain water
      and electrolyte balance in infants with ileostomy.
AB  - INTRODUCTION: Ileostomy represents a necessary procedure to solve various
      surgical diseases in children. As the result of increased fluid loss and colonic
      exclusion in its regulation, it is often followed, particularly during the first
      months after birth, by chronic dehydration and failure to thrive. OBJECTIVE: The
      aim of the paper was to present our experience related to the application of oral
      rehydration solution (ORS) to compensate the intestinal loss of water and
      electrolytes in infants with ileostomy. METHODS: Treatment was performed with ORS
      containing 65 mmol/L of sodium in five infants aged 1.5-8 months (3.8+/-2.46
      months) with dehydration and undernutrition after ileostomy performed in the
      first five days after birth. RESULTS: After rehydration, the continual
      application of ORS in the daily dosage of 63.90+/-25.03 ml/kg, i.e. approximately
      matching the volume of intestinal content elimination (57.00+/-19.23 ml/kg),
      resulted in all infants in optimal water and electrolyte homeostasis, and in
      further course also in the improvement of their nutritional status (p=0.023).
      CONCLUSION: Our experience indicates that continual application of reduced sodium
      content of ORS in the approximate equal quantity of intestinal content loss
      represents the method of choice in water and electrolyte homeostasis maintenance
      in infants with ileostomy.

PMID- 23858802
TI  - [Bone mineral density in children with long-term antiepileptic therapy].
AB  - INTRODUCTION: Vitamin D active metabolites deficit that is al: tered by negative
      calcium and phosphorus balance is a potential complication during long-term
      antiepileptic drug therapy. OBJECTIVE: The aim of this study was to examine
      lumbar bone mineral density (BMD) in epileptic children receiving antiepileptic
      drug therapy longer than one year. METHODS: The examined sample consisted of 34
      epileptic children, 18 male and 16 female, aged 6-12 (9.77+/-2.01) years, treated
      with carbamazepine, valproate, phenobarbital, lamotrigine or their combination
      without vitamin D supplementation. The lumbar spine BMD (L1-L4) was estimated by
      a Lunar densitometer and obtained results were compared with results of 35
      matched population of healthy children from the control group. RESULTS: Lumbar
      BMD Z-score was significantly lower in female patients treated with antiepileptic
      therapy compared with those in the control group (-1.048+/-1.35 vs. -0.399+/
      0.518; p=0.03). Bone mineral density Z-score decrease of both gender groups
      receiving antiepileptic polytherapy was significantly lower compared to the
      control group (-1.153+/-0.938 vs. -0.043+/-0.815; p=0.007). Therapy duration had
      no influence on the lumbar BMD level decrease either in boys (rxy=0.33; p=0.174)
      or in girls (rxy=0.02; p=0.935) treated with antlepileptic therapy. CONCLUSION:
      Our results have indicated that antiepileptic drug therapy usage longer than one
      year can have adverse affects on the lumbar spine BMD (L1-L4) in epileptic
      children, and that prophylactic vitamin D supplementation is also necessary in
      these patients.

PMID- 23858803
TI  - [The efficacy and tolerability of allopurinol dose escalation in patients with
      gout].
AB  - INTRODUCTION: Allopurinol is still the drug of choice for the long-term control
      of hyperuricemia in patients with gout. Objective The aim of the study was to
      investigate the efficacy and tolerability of different allopurinol doses used in
      order to attain a target serum uric acid concentration (SUc) of <6 mg/dl (360
      micromol/L). METHODS: Prospective trial was carried out in patients with primary
      gout and normal renal function, no relevant liver disease, and SUc-lowering
      treatment indications involving 1-2 gout episodes per year, presence oftophus
      and/or chronic urate arthropathy or X-ray finding of erosions. The patients were
      administered allopurinol in a step-up dose scheme (beginning with 100 mg/ day
      then raised for 100 mg every four weeks) until therapeutic goal was achieved or
      development of adverse effects. RESULTS: Forty-one patients were enrolled in the
      study; 27 ended it so far.The treatment target was reached in 19/27 patients
      using allopurinol 300 mg/day (70.4%). After the increased dose up to 600 mg/day,
      the overall treatment success was reached in 25/27 patients (92.5%). Adverse drug
      reactions (ADRs) were evidenced in 12/27 patients; the most frequent ADRs were
      gouty flares. The mean SUc reduction from baseline 533.9+/-83.4 micromol/L to
      346.9+/-87.9 micromol/L was obtained with allopurinol at a dose of 300 mg/day
      (p=0.000) as well as at a dose up to 600 mg/day (274.9+/-92.7 micromol/L)
      (p=0.000). CONCLUSIONS: Most of the investigated gouty patients attained target
      SUc <360 mmol/L at a 300 mg/day allopurinol dose. However, in 30% of patients
      further dose escalation up to 600 mg/day was needed but the increased dose was
      well tolerated, and the therapeutic goal was achieved even in 92.5% of patients.
      Such doses are in general well tolerated under the conditions of well preserved
      renal function.

PMID- 23858804
TI  - [Significance of serum ferritin level in the prediction of delivery of low birth
      weight newborns for gestational age].
AB  - INTRODUCTION: Intrauterine growth restriction is one of the leading causes of
      prenatal morbidity and mortality. As there is no causal therapy, prediction of
      intrauterine growth retardation is one of the priorities of prenatal healthcare.
      OBJECTIVE: The purpose of this study was to analyze blood ferritin level, and
      erythrocyte, hemoglobin and hematocrit count in pregnant women between 30-32
      weeks of gestation and to set apart those with a possible development of
      intrauterine growth restriction. METHODS: A prospective study was conducted that
      included 220 healthy pregnant women between 30-32 gestational weeks. The study
      was done at the Clinical Center of Vojvodina, Department of Obstetrics and
      Gynecology Novi Sad and Clinical laboratory from March 1, 2008 to November 30,
      2009. Serum ferritin level, hemoglobin, hematocrit and erythrocyte count were
      determined from blood samples of all pregnant women. RESULTS: After term
      delivery, 8.1% of pregnant women gave birth to low birth weight babies for
      gestational age but without anemia.The value of ferritin, hemoglobin,
      hematocritanderythrocyte was significantly higher in women with low birth weight
      babies. In mothers with low birth weight newborns serum ferritin level was on the
      average for 6.4 g/l higher than in mothers with normal weight newborns (p<0.005).
      Statistically, ROC curve analysis showed that the pregnant women with the
      ferritin level above 13.6 microg/L, and with erythrocyte count >3.76x10(12)/L,
      hemoglobin >117 g/L and hematocrit >32.9%, in the period of 30-32 weeks of
      gestation, also had a significantly higher probability of having a low birth
      weight newborn for gestational age (p<0.05). CONCLUSION: Based on the level of
      ferritin and other parameters in the period of 30-32 weeks of gestation, we can
      predict pregnant women in whom we can expect development of intrauterine growth
      restriction.

PMID- 23858805
TI  - Collagen type I alpha 1 gene polymorphism in premature ovarian failure.
AB  - INTRODUCTION: Premature ovarian failure (POF) is characterized by amenorrhea,
      hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is
      one of the late complications of POF. OBJECTIVE: To correlate collagen type I
      alpha1 (COLIA1) gene polymorphism with bone mineral density (BMD) in women with
      POF. METHODS: We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF.
      Single nucleotide polymorphism (G toT substitution) within the Sp 1-binding site
      in the first intron of the COLIA1 gene was assessed by polymerase chain reaction
      (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis. Bone
      mineral density (BMD) was measured at the lumbar spine region by dual X-ray
      absorptiometry. STATISTICS: Kruskal-Wallis ANOVA, Chi-square test, Spearman
      correlation test. RESULTS: The relative distribution of COLIA1 genotype alleles
      was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found
      between genotype groups in body mass index, age, duration of amenorrhea or BMD. A
      significant positive correlation was observed between BMI and parity. CONCLUSION:
      The COLIA1 gene is just one of many genes influencing bone characteristics. It
      may act as a marker for differences in bone quantity and quality, bone fragility
      and accelerated bone loss in older women. However, in young women with POF,
      COLIA1 cannot identify those at higher risk for osteoporosis.

PMID- 23858806
TI  - [Nasal carriage of methicillin-resistant Staphylococcus aureus among medical
      students of Belgrade University].
AB  - INTRODUCTION: Infections caused by methicillin-resistant Staphylococcus aureus
      (MRSA) present the growing problem in the whole world. Carriage of MRSA is most
      frequent in the nose, and medical students come in contact both with patients and
      different persons in the community. Therefore, they may be significant for the
      transmission of MRSA from hospitals to out-of-hospital communities and vice
      versa. OBJECTIVE: The aim of this study was to establish the carriage rate among
      students of the second, third and fourth year of study at the School of Medicine
      in Belgrade and to analyze their genotypic and phenotypic characteristics.
      METHODS: In total 533 nasal samples were taken. The samples were incubated
      inTrypcase-soy broth supplemented with 6.5% NaCl, and thereafter the swabs were
      inoculated on mannitol salt agar supplemented with 2 microg/mL of oxacillin. The
      presence of nuc, mecA and Panton-Valentine leukocidin genes was examined by
      PCR.The characteristics of the MRSA strains were determined using: antibiotic
      susceptibility testing by Vitek2 System, SCCmec, agr typing and MLST. RESULTS:
      MRSA was isolated from two of 533 investigated samples (0.37%). MRSA were
      isolated from the students of the second and third year of study. Profiles of
      strains were: ST80 (SCCmec type IV, agr type 3) and ST152 (SCCmec type V, agr
      type 1). MRSA strains were multiresistant. CONCLUSION: The nasal carriage rate of
      MRSA in population of medical students of the first year of study in Belgrade is
      low. Genotypic and phenotypic characteristics of MRSA strains indicate their
      community origin. MLST typing revealed that isolates belong to ST80 and ST152.

PMID- 23858807
TI  - Etiological aspect of left-handedness in adolescents.
AB  - INTRODUCTION: Lateralization of brain functions such as language and manual
      dominance (hand preferences and fine motor control) are most likely under genetic
      control. However, this does not preclude the effect of various environmental
      factors on functional brain lateralization. A strong association of non-right
      handedness (left- and mixed-handedness) with various neurodevelopmental
      conditions (e.g. schizophrenia, autism, Rett syndrome) implies that in some
      cases, non-right-handedness may be acquired rather than inherited (i.e.,
      pathologically determined). OBJECTIVE: The aim of the study was: (a) re
      investigation of several known risk factors for left-handedness (age of mother
      and/or father, twin pregnancies, and birth order), and (b) examination of
      hitherto uninvestigated factors (type of birth, Apgar score, maternal smoking
      during pregnancy). METHODS: Putative, causative environmental agents for this
      shift in manual distributions are explored in a sample of 1031 high school
      students (404 males and 627 females) from Belgrade. Both pre-existing (age of
      parents, twin pregnancy, and birth order) and new (Apgar score, maternal smoking,
      type of birth) putative agents are examined. RESULTS: We found that maternal
      smoking and low Apgar score (2-6) can significantly increase risk for left
      handedness (p=0.046 and p=0.042, respectively).The remaining factors showed no
      significant association with left-handedness in adolescents. CONCLUSION: Our
      study clearly demonstrates that left-handedness may be related to maternal
      smoking during pregnancy and a low Apgar score on birth.

PMID- 23858808
TI  - [Drunken state in fatally injured drivers of motor vehicles].
AB  - INTRODUCTION: Consumption of alcohol may be an important causative factor in
      traffic accidents, particularly in categories of drivers and pedestrians.
      OBJECTIVE: Analysis of frequency and other important medicolegal characteristics
      of drunken state of motor vehicles drivers. METHODS: We analyzed autopsibs
      performed at the Institute of Forensic Medicine Belgrade during 2008 and 2009.
      Data were obtained from autopsy protocols, results of toxicological examinations,
      and police reports about circumstances of traffic accidents. RESULTS: Out of all
      84 fatally injured drivers, drunken state was proved in 31 (36.9%).The majority
      of them were males (30% or 97%), while only one female driver was under the
      influence of alcohol.The most often drunken drivers were in the third life decade
      (10% or 32.2%). In most cases the injured alcoholised drivers died immediately
      after the accident (83.8%). In most of them blood alcohol concentration (BAC) was
      higher than 2 per thousand (58.1%), most frequently (12) BAC varied between 2.1
      per thousand and 2.5 per thousand, and the highest determined BAC was 3.85 per
      thousand. The majority of accidents occurred between midnight and 6 a.m. (54.8%),
      mostly during working days (77.4%). The most frequent ways of the occurrence of
      traffic accidents were driving by turning away from the road and striking from
      behind another vehicle on the road. CONCLUSION: The obtained results point out
      the important role of the drunken state of the drivers of motor vehicles as a
      causative factor in traffic accidents in our population. The potentially
      effective preventive measure could be absolute prohibition of alcohol consumption
      for all drivers.

PMID- 23858809
TI  - Serbian translation of the 20-item Toronto Alexithymia Scale: psychometric
      properties and the new methodological approach in translating scales.
AB  - INTRODUCTION: Since inception of the alexithymia construct in 1970's, there has
      been a continuous effort to improve both its theoretical postulates and the
      clinical utility through development, standardization and validation of
      assessment scales. OBJECTIVE: The aim of this study was to validate the Serbian
      translation of the 20-item Toronto Alexithymia Scale (TAS-20) and to propose a
      new method of translation of scales with a property of temporal stability.
      METHODS: The scale was expertly translated by bilingual medical professionals and
      a linguist, and given to a sample of bilingual participants from the general
      population who completed both the English and the Serbian version of the scale
      one week apart. RESULTS: The findings showed that the Serbian version of the TAS
      20 had a good internal consistency reliability regarding total scale
      (alpha=0.86), and acceptable reliability of the three factors (alpha=0.71-0.79).
      CONCLUSION: The analysis confirmed the validity and consistency of the Serbian
      translation of the scale, with observed weakness of the factorial structure
      consistent with studies in other languages. The results also showed that the
      method of utilizing a self-control bilingual subject is a useful alternative to
      the back-translation method, particularly in cases of linguistically and
      structurally sensitive scales, or in cases where a larger sample is not
      available. This method, dubbed as 'forth-translation' could be used to translate
      psychometric scales measuring properties which have temporal stability over the
      period of at least several weeks.

PMID- 23858810
TI  - [Pars plana vitrectomy with extraction of intraocular foreign body in patients
      with siderosis of the eye: report of two cases].
AB  - INTRODUCTION: Penetrating injury is characterized by the existence of entry wound
      only, and it can be with or without an intraocular foreign body (IOFB). IOFB can
      lead to a mechanical injury of the eye and to cause infection or to manifest
      other toxic effects on intraocular structures. Iron and copper can dissolve and
      cause siderosis, i.e. chalcosis of the eye. Ocular siderosis is diagnosed by
      clinical and electroretinogram (ERG) findings. OUTLINE OF CASES: The first
      patient was a 37-year-old male who was injured by a metal foreign body. He
      presented at the Clinic two years after the injury. Visual acuity of the right
      eye (VOD) on admission was VOD=L+P+ (light projection). Pars plana phaco
      vitrectomy with IOFB extraction was done. Visual acuity on discharge was VOD=3/60
      cc + 7.50 Dsph=0.2. The second patient was a 55-year-old male who presented at
      the clinic 18 months after injury. On admission visual acuity in his left eye was
      VOS 1/60. Pars plana phacovitrectomy with IOFB extraction was done.Visual acuity
      on discharge was VOS=0.7 through the stenopeic slit. CONCLUSION: In penetrating
      injuries caused by a metal IOFB pars plana vitrectomy with IOFB extraction is
      indicated. In cases with IOFB, when visual acuity is preserved, the lens is
      transparent, while the eye is without signs of infection, urgent pars plana
      vitrectomy is not necessary. Such patients need regular followup with obligatory
      ERG findings.

PMID- 23858811
TI  - [Optimal postoperative radiotherapy treatment of orbital rhabdomyosarcoma].
AB  - INTRODUCTION: Rhabdomyosarcoma (RMS) is the most common sarcoma of the soft
      tissue, mostly affecting the region of head and neck (orbit, paranasal sinus).
      Histological types include embryonal (66-70%) with better prognosis, and alveolar
      type (20%) with poorer prognosis. There are also diffuse anaplastic and
      undifferentiated sarcomas (10%). Due to multimodal therapy approach (surgery,
      chemotherapy and radiotherapy), RMS survival rate is considerably improving.
      Nevertheless, early diagnosis of RMS is of crucial importance for the outcome of
      treatment. Standard conformal radiation therapy is very complex due to closeness
      of many critical structures of head and neck, thus limiting optimal tumor dose
      coverage. CASE OUTLINE: Patient aged 59 years, surgically treated for RMS of
      nasal cavity several times before radiation therapy treatment. Due to relapse,
      patient was re-operated, when subtotal re-resection of the maxilla with
      exenteration of the right orbit was done. The patient received IV cycles of
      polychemotherapy postoperatively. Standard procedure and planning for conformal
      radiation therapy did not lead to acceptable irradiation plan, and hence
      modification in the patient's preparation was done, resulting in optimal
      therapeutic plan according to internationally recognized recommendations.
      CONCLUSION: The reported case shows a rare pediatric tumor, which often occurs in
      children but extremely rare in adults. The problem of inadequate isodose
      distribution obtained by standard conformal plan was solved by placing bolus
      material into the orbital cavity.The outcome of the treatment plan showed much
      better isodose distribution and tumor bed coverage.

PMID- 23858812
TI  - [Solid solitary hamartoma of the spleen].
AB  - INTRODUCTION: Hamartoma of the spleen is a rare, sometimes asymptomatic similar
      to hemangioma benign tumor of the spleen, which, owing to the new diagnostic
      imaging methods, is discovered with increasing frequency. It appears as solitary
      or multiple tumorous lesions. CASE OUTLINE: We present a 48-year-old woman in
      whom, during the investigation for Helicobacter pylori gastric infection and
      rectal bleeding, with ultrasonography, a mass 6.5x6.5 cm in diameter was
      discovered by chance within the spleen. Splenectomy was performed due to
      suspected lymphoma of the spleen. On histology, tumor showed to be of mixed
      cellular structure, with areas without white pulp, at places with marked
      dilatation of sinusoids and capillaries to the formation of "blood lakes" between
      which broad hypercellular Billroth's zones were present. Extramedullary
      hematopoiesis was found focally. The cells that covered vascular spaces were
      CD34+ and CD31+ and CD8- and CD21-. CONCLUSION: Hamartoma has to be taken into
      consideration always when well circumscribed hypervascular tumor within the
      spleen is found, particularly in children. Although the diagnosis of hamartoma
      may be suspected preoperatively, the exact diagnosis is established based on
      histological and immunohystochemistry examinations. Treatment is most often
      splenectomy and rarely a partial splenectomy is possible, which is recommended
      particularly in children.

PMID- 23858813
TI  - Solid and cystic pseudopapillary tumor of the pancreas: A case report.
AB  - INTRODUCTION: Solid and cystic pseudopapillary tumor of the pancreas is a rare
      tumor of the pancreas, for the first time described by Frantz et al. in 1959. The
      majority of patients are young females and most of them are asymptomatic. CASE
      OUTLINE: We report a case of 25-year old woman who was admitted to our
      institution with abdominal pain and a palpable mass in the left hypochondrial
      area. US and CT scan revealed a solid and cystic pseudopapillary tumor in the
      head of the pancreas. The patient was treated by Whipple procedure, modification
      Longmire-Traverso. There was no metastatic disease either in the liver or
      peritoneum. Histologically the tumor was diagnosed as a solid and cystic
      pseudopapillary tumor of the pancreas. CONCLUSION: The unclear pre-operative
      diagnoses, together with incidence of potential malignancy as well as good
      outcome with resection, suggest that all suspected cystic tumors of the pancreas
      should be resected.The exact diagnosis is based on histological findings.

PMID- 23858814
TI  - Simvastatin-lnduced nocturnal leg pain disappears with pravastatin substitution.
AB  - INTRODUCTION: Statins have similar side effects that do not always occur at the
      same rate among the various statins. We present a case of simvastatin-induced
      muscle toxicity that disappeared when pravastatin was substituted for the
      original drug. CASE OUTLINE: A 74-year-old male, a nonsmoker, complained of
      severe nocturnal leg cramps. The patient also complained that similar painful
      cramping occurred when he walked rapidly or jogged. Because some components of
      his lipid panel exceeded the'desirable' range, and as he had a history of
      myocardial infarction, his family physician prescribed simvastatin (40 mg/day).
      The patient had taken this medication for the past eight years. The painful
      nocturnal episodes started two years ago and affected either one or the other
      leg. Four months ago we discontinued his simvastatin and prescribed pravastatin
      (80 mg/day). At a follow-up visit six weeks later, the patient reported that his
      leg pains at night and the pain experienced after brisk walking had disappeared.
      Four months after the substitution of pravastatin for simvastatin, the patient
      reported that his complete lack of symptoms had continued. CONCLUSION: These
      painful muscle cramps were probably caused by an inadequate vascular supply to
      the calf and foot muscles. Perhaps a combination of advanced age and
      atherosclerotic changes created a predisposition for the simvastatin-induced leg
      cramps. Pravastatin differs from simvastatin in several ways.l It is not
      metabolized by cytochrome P450 (CYP) 3A4 oxidases, and thus is not influenced by
      CYP 3A4 inhibitors like simvastatin. Also, simvastatin is associated with single
      nucleotide polymorphisms located within the SLCO1B1 gene on the chromosome 12 and
      established myopathy, while pravastatin lacks this association. These differences
      may contribute to increased tolerance to pravastatin in this particular case.

PMID- 23858815
TI  - [Treatment of infantile tibia vara - 18-year follow-up: A case report].
AB  - INTRODUCTION: Blount disease is developmental disorder of the lower leg,
      manifested by multiplanar deformity. Surgical treatment includes corrective
      osteotomy, lateral hemiepiphisyodesis, distraction of the proximal tibial physis,
      physeal bar resection and elevation of the medial tibial plateau. CASE OUTLINE: A
      case of a 4-year-old girl with bow legs is presented. Condition was recognized as
      Blount disease, type five. Both lower legs were operated by medial methaphyseal
      semi-osteotomy of the proximal tibia with the elevation of the medial tibial
      plateau. Prospectively, bilateral proximal hemiepiphysiodesis was done. Total
      follow-up period was eighteen years.The patient has no disturbances, clinical and
      radiographic findings are excellent. Improvement of the femoro-tibial angle is 22
      degrees on the right side, and 21 degrees on the left side. Improvement of the
      varus angle is 7 degrees on the right side, and 27 degrees on the left side.
      Medial plateau depression is completely bilaterally reduced; improvement on the
      right side is 46 degrees, and 51 degrees on the left side. CONCLUSION: It is
      known today that multiplanar deformity is a part of the disease; varus,
      antecurvatum and internal rotation of the lower leg. By elevation of the medial
      plateau varus of the lower and antecurvatum component of deformity can be solved,
      while internal torsion cannot be solved. This deformity has to be either
      skillfully neglected, or corrected by an additional osteotomy by the elevation of
      the medial tibial plateau. Lateral hemiepiphysiodesis serves as extra
      stabilisator of the achieved result, and it is recommended to be done in
      combination with surgical elevation of the medial tibial plateau and derotative
      corrective osteotomy of the tibia.

PMID- 23858816
TI  - Dilemmas in zirconia bonding: A review.
AB  - This article presents a literature review on the resin bond to zirconia ceramic.
      Modern esthetic dentistry has highly recognized zirconia, among other ceramic
      materials. Biocompatibility of zirconia, chemical and dimensional stability,
      excellent mechanical properties, all together could guarantee optimal
      therapeutical results in complex prosthodontic reconstruction. On the other hand,
      low thermal degradation, aging of zirconia as well as problematic bonding of
      zirconia framework to dental luting cements and tooth structures, opened the room
      for discussion concerning their clinical durability.The well known methods of
      mechanical and chemical bonding used on glass-ceramics are not applicable for use
      with zirconia. Therefore, under critical clinical situations, selection of the
      bonding mechanism should be focused on two important points: high initial bond
      strength value and long term bond strength between zirconia-resin interface.
      Also, this paper emphases the use of phosphate monomer luting cements on freshly
      air-abraded zirconia as the simplest and most effective way for zirconia
      cementation procedure today.

PMID- 23858817
TI  - [The role of breast magnetic resonance imaging in the diagnosis of ductal
      carcinoma in situ].
AB  - Ductal carcinoma in situ (DCIS), the noninvasive breast malignant tumor
      originates from the terminal ductal-lobular units (TDLU). The typical feature of
      DCSI is the formation of calcifications. Up to 90% of DCIS are diagnosed on
      mammographic examinations, as clinically asymptomatic. Between 10% and 20% of
      DCIS remain mammographically occult due to the lack of calcifications and/ or
      small tumor dimensions. Contrast-enhanced breast magnetic resonance imaging (MRI)
      detects mammographically occult breast lesions, thus defining morphologic
      features of the lesion and the dynamics of signal intensity changes due to
      contrast enhancement. Distribution of contrast enhancement - signal intensity
      increase in DCIS most frequently includes segmental, ductal and linear patterns,
      followed by regional enhancement pattern, while the intralesional contrast uptake
      most frequently includes the nodular pattern with the areas of confluence.
      Postcontrast signal intensity increase in DCIS is most frequently fast in the
      initial phase (wash-in), while the whole dynamic of contrast-enhancement includes
      either of the three possible time-intensity curve (TIC) types (persistent,
      plateau or washout), although the plateau TIC is considered to be more frequent.
      Breast MRI has high sensitivity in the diagnosis of invasive breast cancer,
      varying from 90% to 100%; the sensitivity in the diagnosis of DCIS is lower (77
      96%). For the time being, the primary role of MRI in DCIS is planning of breast
      conserving surgery (BCS) for the evaluation of lesion extension. Further
      development of MRI in the diagnosis of DCIS includes the implementation of the
      principles of functional and molecular imaging.

PMID- 23858818
TI  - [The mechanism of injuring of front-seat passengers in head-on motor vehicle
      collisions: forensic issues].
AB  - Forensic pathologists sometimes need to determine seating positions of automobile
      occupants after road traffic accidents as accurately as possible. That could be
      of essential significance particularly in regard to the question of guilt both in
      the criminal and civil law. So far, medical surveys have implied the specific
      injury which would undoubtedly point at the allocation of the seating positions
      of fatally injured car occupant. Some of the injuries could occur by both direct
      and indirect force action. Same type of injury of the specific body region in
      both drivers and front seat passengers could occur by different mechanism and in
      different phases of the accident. Sometimes neither the order of injury
      occurrence remains unclear, nor whether some of the injuries are post-mortal.
      What makes it even harder is the fact that same body regions, i.e. head and
      thorax, are most affected in both drivers and front seat passengers, and that
      these injuries are often fatal. Even if the victim survives the accident for some
      time and later dies in hospital, the possibility of accident reconstruction and
      determination of car occupants seating position at the moment of accident
      declines with the time length of survival period. Examining the victims' clothes,
      searching for biological traces, technical expert inspection of the vehicle,
      traffic expert analysis of the site, enables adequate reconstruction of the
      traffic accident. All this implies that in such cases the knowledge of underlying
      mechanism of car occupants' injury is insufficient, and that a close cooperation
      between forensic pathologists and the team of other forensic technical experts is
      necessary.

PMID- 23858820
TI  - A profession's treasure.

PMID- 23858819
TI  - [Development of forensic psychiatry in Serbia].
AB  - The development of legislation in the field of mental health in our region is
      linked with the emergence and development of the oldest psychiatric hospitals in
      Serbia.The principle that the mentally ill who committed a criminal offense need
      to be placed in a psychiatric hospital instead of a prison was introduced at the
      same time as in the most developed European countries. The founders of the
      Serbian forensic psychiatry, Dr. Jovan Danic, Dr.Vojislav Subotic Jr. and Dr.
      Dusan Subotic, were all trained at the first Serbian Psychiatric Hospital ("Home
      for the Unsound of Mind") that was founded in 1861 in the part of Belgrade called
      Guberevac. Their successors were psychiatric enthusiasts Prof. Dr.Vladimir
      F.Vujic and Prof. Dr. Laza Stanojevic. A formal establishment of the School of
      Medicine of Belgrade, with acquirement of new experience and positive shifts
      within this field, based on the general act of the University in 1932, led to the
      formation of the Council of the School of Medicine, which, as a collective body
      passed expert opinions. Thus, the first Forensic Medicine Committee of the School
      of Medicine was formed and started its activities in 1931 when Forensic Medicine
      Committee Regulations were accepted. After the World War II prominent educators
      in the field of mental health, and who particularly contributed to further
      development of forensic psychiatry in Serbia were Prof. Dr. Uros Jekic, Prof Dr.
      Dusan Jevtic, Dr. Stevan Jovanovic, Prof. Dr. Borislav Kapamadzija, Prof. Dr.
      Maksim Sternic, Prof. Dr. Josif Vesel and Prof. Dr. Dimitrije Milovanovic.

PMID- 23858821
TI  - A comparison of student knowledge acquisition by organ system and skills in
      parallel problem-based and lecture-based curricula.
AB  - PURPOSE: A 5-year longitudinal study was conducted of students' acquisition of
      knowledge by organ system and skill development between two curricular tracks:
      problem-based learning (PBL) and lecture-based learning (LBL). Analysis of these
      data is reported. METHODS: A comprehensive examination was administered to all
      students enrolled in the LBL and PBL curricular tracks on five occasions: 0, 4,
      8, 12, and 24 months. The organ-system and skills subtest scores from these
      comprehensive examinations and the Physician Assistant National Certifying Exam
      were compared. RESULTS: Organ-system subtests: Of the 12 organ-system subtests
      measured, there was a statistically significant difference between the LBL and
      PBL curricula in the mean test scores for one subtest (psychiatric). In addition,
      there were significant differences in all organ-system subtests by time, and
      finally there was a curriculum by time interaction in 10 of 12 subtests. Skills
      subtests: There were statistically significant differences in the mean test
      scores for one of seven subtests (applying scientific concepts), as well as
      significant differences in all skills subtests by time and a curriculum by time
      interaction in six of seven subtests. CONCLUSIONS: Statistical differences
      observed could mostly be explained by differences in knowledge on program entry
      or in time of exposure to curricular content. The importance of clinical training
      was evidenced in some organ systems, particularly reproductive and psychiatric.
      More uniform learning appears to occur in skills education, and there is evidence
      that the PBL model provides a sound grounding in the application of basic
      science.

PMID- 23858822
TI  - The use of noncognitive factors in physician assistant admissions.
AB  - PURPOSE: To identify the most influential noncognitive factors valued in
      admissions processes by physician assistant (PA) programs throughout the United
      States, as well as the motivators for and barriers to using these factors.
      METHODS: A literature search was performed using PubMed and the Journal of
      Physician Assistant Education to identify noncognitive factors that were reported
      to have an effect on admissions in various health professions. A survey was
      developed incorporating the most frequently identified factors and was
      electronically distributed to all program directors of the Physician Assistant
      Education Association (PAEA). Respondents were asked to rank the noncognitive
      factors that were most valued by their program's admissions process as well as to
      rate motivators and barriers for the use of these noncognitive factors in
      admissions. Survey responses were anonymous but respondents reported program
      location by geographic region as defined by PAEA. RESULTS: There were 94
      respondents from 154 programs surveyed (61% response rate). The five most
      influential noncognitive factors were faculty/staff/interviewer interactions,
      career motivation, knowledge of profession, maturity, and professionalism. The
      most important motivators for using noncognitive factors were identified as
      academic success and career success. All aforementioned factors and motivators
      did not vary based on PA program region (P > .05). The factors identified with
      the highest level of regional variance were leadership experience (P = .014),
      self-awareness (P = .034), cultural sensitivity (P = .022), undergraduate
      institution (P = .010), and peer interaction (P = .035). CONCLUSION: These study
      results will assist PA applicants in becoming more competitive and provide
      programs with additional factors for consideration in current admissions
      practices. Further considerations for research include correlating results to
      academic success as well as success on the Physician Assistant National
      Certifying Exam (PANCE).

PMID- 23858823
TI  - The relationship between formative and summative examination and PANCE results: a
      multi-program study.
AB  - PURPOSE: This correlational research study was conducted to validate externally a
      previous pilot study that examined the relationship between formative and
      summative examinations and PANCE scores at one physician assistant (PA) program.
      The study was expanded to five PA programs to test the hypothesis that PA
      programs throughout the country could use comprehensive examinations that
      mirrored the Physician Assistant National Certifying Exam (PANCE) along with the
      Physician Assistant Clinical Knowledge Rating and Assessment Tool (PACKRAT)
      scores to predict future PANCE performance successfully. METHODS: The six
      participating PA programs administered the SUMM I, which is a 360-question PANCE
      simulation exam based upon the National Commission on Certification of Physician
      Assistants (NCCPA) blueprint, the SUMM II, a 700-question examination based upon
      the NCCPA blueprint, and the PACKRAT examination to all second-year students.
      Participating programs were provided cut scores for each of the test instruments
      that identified students at critical risk for failing the PANCE. RESULTS: The
      scores of the study participants from the originating institution were gathered
      between 2007 and 2010 and from five additional programs in 2011-2012 to determine
      correlational strength between the instruments and the PANCE. The SUMM I, SUMM
      II, and PACKRAT scores (N = 421) were combined in a regression model to generate
      a predicted PANCE score. The strength of correlation between the predicted PANCE
      score and actual PANCE score demonstrated an Rvalue of 0.79 and an R2 Of 0.62.
      DISCUSSION: This correlational study suggests that summative examination
      instruments can be developed and triangulated with PACKRAT scores to predict
      future performance on the PANCE and determine thresholds of risk for failing the
      PANCE based upon stratified levels of past performance.

PMID- 23858824
TI  - Physician assistant students' views regarding interprofessional education: a
      focus group study.
AB  - PURPOSE: The purpose of this study was to identify and report physician assistant
      (PA) student experiences, learning, and opinions regarding interprofessional
      education (IPE). METHODS: A series of open-ended questions was constructed and
      designed to solicit PA students' opinions about the need for IPE, preferred
      teaching strategies, and implementation methods, using focus group methodology.
      We used two sets of questions, one for students who had participated in a formal
      geriatrics IPE experience (n = 12), the other for students who did not have the
      experience (n = 10). Focus group sessions were audiotaped and transcripts coded.
      Key themes were identified and ranked. RESULTS: Twenty-two students participated
      in four focus groups. Theme saturation was reached and six overlapping themes
      emerged: (1) PA students learned the most about occupational and physical
      therapist roles; (2) They were surprised at other professions' lack of knowledge
      about the PA profession; (3) They strongly expressed that IPE should be required
      early in training; (4) They expressed preference for direct patient care with
      other health professions students, with trained faculty oversight; (5) They
      requested diverse clinical settings; and (6) They identified the optimal number
      of different students in a single IPE experience as four/five. The group exposed
      to geriatrics IPE noted the critical importance of faculty training for
      facilitation, while the nonexposed group emphasized the challenge of limited
      curricular time. CONCLUSION: PA students recognize the importance of IPE and
      request early, required clinical experiences led by well-trained
      interprofessional faculty with the option to choose clinical sites. Student
      preferences should be considered in IPE curriculum design.

PMID- 23858825
TI  - Correlations between PANCE performance, physician assistant program grade point
      average, and selection criteria.
AB  - PURPOSE: The purpose of this study was to examine correlations between first-time
      Physician Assistant National Certifying Exam (PANCE) scores and pass/fail status,
      physician assistant (PA) program didactic grade point average (GPA), and specific
      selection criteria. METHODS: This retrospective study evaluated graduating
      classes from 2007, 2008, and 2009 at a single program (N = 119). RESULTS: There
      was no correlation between PANCE performance and undergraduate grade point
      average (GPA), science prerequisite GPA, or health care experience. There was a
      moderate correlation between PANCE pass/fail and where students took science
      prerequisites (r = 0.27, P = .003) but not with the PANCE score. PANCE scores
      were correlated with overall PA program GPA (r = 0.67), PA pharmacology grade (r
      = 0.68), and PA anatomy grade (r = 0.41) but not with PANCE pass/fail.
      CONCLUSIONS: Correlations between selection criteria and PANCE performance were
      limited, but further research regarding the influence of prerequisite institution
      type may be warranted and may improve admission decisions. PANCE scores and PA
      program GPA correlations may guide academic advising and remediation decisions
      for current students.

PMID- 23858827
TI  - Ethical tools for physician assistant students: implementation of palliative care
      training in an ethical framework.

PMID- 23858826
TI  - Number-needed-to-treat: translating benefits and risks of therapy from clinical
      trials to a clinical encounter.

PMID- 23858828
TI  - UV-nanoimprint lithography: structure, materials and fabrication of flexible
      molds.
AB  - Large-area nanopatterning technology has demonstrated high potential which can
      significantly enhance the performance of a variety of devices and products such
      as LEDs, solar cells, hard disk drives, laser diodes, wafer-level optics, etc.
      But various existing patterning technologies cannot well meet industrial-level
      application requirements in term of high resolution, high throughput, low cost,
      large patterned areas, and the ability to pattern on non-ideal surfaces or
      waters. Soft UV-nanoimprint lithography (UV-NIL) by using a flexible mold has
      been proven to be a cost-effective mass production method for patterning large
      area structures up to wafer-level (300 mm) in the micrometer and nanometer scale,
      fabricating complex 3-D micro/nano structures, especially making large-area
      patterns on the non-planar surfaces even curved substrates at low-cost and with
      high throughput. In particular, it provides an ideal solution and a powerful tool
      for mass producing micro/nanostructures over large areas at low cost for the
      applications in compound semiconductor optoelectronics and nanophotonic devices,
      especially for LED patterning. That opens the way for many applications not
      previously conceptualized or economically feasible. The flexible mold is the most
      critical elements for soft UV-NIL. The performance of the flexible mold has a
      decisive effect on the soft UV-NIL in term of resolution, patterning area,
      throughput, uniformity of the imprinted patterns, and repeatability of multi
      imprinting. The key enabler that can fulfill mass production of micro-and
      nanostructures over large areas by NIL is the continual advancement of mold
      techniques (structures, materials and fabrication processes) towards higher
      resolution over a larger area at a lower cost. This paper provides a
      comprehensive review on the structural types, materials used and fabrication
      methods of various flexible molds in soft UV-NIL, surveys major progress in
      various flexible molds, particularly highlights some concluding remarks and
      generalizations. Two key issues for flexible molds, deformation mechanism and
      controlling solution of soft molds as well as fabrication of large area (wafer
      level) master template, are described in detail. Furthermore, prospects,
      challenges and future directions for flexible molds are addressed. Finally, some
      potential or promising solutions for improving the performance of flexible molds
      and soft UV-NIL process, as well as some important conclusions are presented.

PMID- 23858829
TI  - Quantum dots for light emitting diodes.
AB  - In this article we discuss the development and key advantages of quantum dot
      based light emitting diode (QD-LED) and other applications based on their color
      purity, stability, and solution processibility. Analysis of quantum dot based
      LEDs and the main challenges faced in this field, such as the QD luminescence
      quenching, QD charging in thin films, and external quantum efficiency are
      discussed in detail. The description about how different optical down-conversion
      and structures enabled researchers to overcome these challenges and to
      commercialize the products. The recent developments about how to overcome these
      difficulties have also been discussed in this article.

PMID- 23858830
TI  - Long non-coding RNAs and prostate cancer.
AB  - A new class of transcripts, long non-coding RNAs (IncRNAs), has been recently
      found to be pervasively transcribed in the genome. These mRNA-like molecules,
      which lack significant protein-coding capacity, once thought to be a part of the
      dark matter, now have been implicated in a wide range of biological functions
      through diverse and as yet poorly understood molecular mechanisms. Multiple
      facets of evidence increasingly link mutations and dysregulations of IncRNAs to
      prostate cancer (PCA). Despite some recent insights into how IncRNAs function in
      such diverse cellular processes as regulation of gene expression and assembly of
      cellular structures, by and large, the key questions regarding IncRNA mechanisms
      remain to be answered. In this review, we analysis recent advances in
      understanding the biological functions of IncRNAs especially in PCA and propose
      avenues of investigation that may lead to fundamental new insights into their
      functions and mechanisms of action. Finally, as numerous IncRNAs are dysregulated
      and disorders in PCA, we also discuss potential roles for these molecules in PCA
      and hope that can be used in clinic by nanotechnology.

PMID- 23858831
TI  - The complex roles of microRNAs in the metastasis of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for approximately 3% of cancers in adults as
      well as the most common neoplasm of the adult kidney with the highest mortality
      rate at over 40%. Metastasis is the most significant process affecting the
      clinical management of RCC patients. It occurs in multiple sequential steps.
      However, the molecular pathways underlying each step still remain obscure. Recent
      researches have shown that microRNAs (miRNAs) function as regulators in
      metastasis of RCC. In this article, we review the role of miRNAs in metastasis of
      RCC, including: specific miRNA signatures of metastatic RCC, metastasis
      associated targets and pathways of miRNAs in RCC, miRNAs participate in
      epithelial-mesenchymal transition (EMT), miRNA DNA methylation signature in RCC
      metastasis and so on. MiRNAs are potential to serve as powerful biomarkers of RCC
      metastasis and novel therapeutic targets in RCC treatment.

PMID- 23858832
TI  - Surface-engineered magnetic nanoparticles for molecular detection of infectious
      agents and cancer.
AB  - Magnetic nanoparticles (MNPs), especially superparamagnetic iron oxide
      nanoparticles (SPIONs), have long been studied as contrast agents for magnetic
      resonance imaging (MRI). Owing to recent progress in synthesis and surface
      modification, many new avenues have opened for this class of biomaterials. Such
      nanoparticles are not merely tiny magnetic crystals, but potential platforms with
      large surface-to-volume ratios. By taking advantage of the well developed surface
      chemistry of MNPs, a wide range of functionalities, such as targeting, imaging,
      detection and therapeutic features, can be loaded onto their surfaces. This
      property makes magnetic nanoparticles excellent biomaterials for molecular
      detection of infectious agents and cancer. This short review thus discusses
      current advances on magnetic nanoparticles as molecular detection agents for
      infectious agents and cancer.

PMID- 23858833
TI  - Cardiovascular effects of pulmonary exposure to titanium dioxide nanoparticles in
      ApoE knockout mice.
AB  - Existing studies on the inhalation toxicology of titanium dioxide (TiO2) have
      focused on possible carcinogenic capacity; however researches on the
      cardiovascular effect are limited, particularly in terms of susceptible animal
      models. The present study examined the inhalation toxicology of nano-TiO2 in ApoE
      knockout mice (ApoE-/- mice), an atherosclerosis susceptible animal model. The
      nano-TiO2 particles used were anatase type and the diameter ranged from 5 to 10
      nm. ApoE-/- mice were randomly divided into five groups (high dose group, median
      dose group, low dose group, PBS vehicle control group and the nontreatment
      control group), each of which were given tracheal instillation of nano-TiO2 at
      the dose of 100 microg, 50 microg and 10 microg and PBS solution per week
      respectively, totally for six weeks, while the nontreatment control group
      received no tracheal instillation. We measured various indicators of
      inflammation, endothelial dysfunction and lipid metabolism in serum, and
      determined plaque formation on the aorta. After six weeks of treatment, there was
      significant difference between the high dose group and PBS control group in terms
      of C reactive protein (CRP), nitric oxide (NO), endothelial nitric oxide
      synthases (eNOS), total cholesterol (TC) and high density lipoprotein cholesterol
      (HDL-C) in serum. The results also showed ratio of plaque area to luminal area
      and the ratio of the lipid-rich core area to plaque area in the median and high
      nano-TiO2 dose group significantly increased respectively in HE stained cross
      sections. Our study showed that tracheal instillation of nano-TiO2 particles
      induced considerable systemic inflammation, endothelial dysfunction and lipid
      metabolism dysfunction, contributing to the progression of atherosclerosis.

PMID- 23858834
TI  - Silica coated gold nanorods for imaging and photo-thermal therapy of cancer
      cells.
AB  - Due to their efficient conversion of absorbed light energy to heat gold nanorods
      have been proved to be an amazing tool for minimally invasive photo-thermal
      cancer therapy. The present in vitro study demonstrates the ability of silica
      coated Au nanorods to function as a dual probe for cancer-cell therapy and
      imaging without any toxic side-effects. HeLa cells were incubated with silica
      coated Au nanorods and imaged inside the cell just after 1 hour of incubation by
      a dark field set up due to strong surface enhanced Raman scattering. To induce
      hyperthermia, silica coated Au nanorod incubated HeLa cells were illuminated with
      a diode laser (671 nm, 200 mW, 10 min). Cell destruction was observed even at a
      very low dose of nanorods, whereas none was observed in the absence of nanorods.
      Silica coated Au nanorods thus offer a promising, novel class of selective photo
      thermal agents for cancer therapy and diagnosis.

PMID- 23858835
TI  - Luminescence properties of europium ions-doped yttrium silicate (Y2SiO5:Eu3+)
      nanocrystalline phosphors: effect of Eu3+ ion concentration and thermal
      annealing.
AB  - The trivalent europium ions-doped yttrium silicate (Y2SiO5:Eu3+) nanocrystalline
      phosphors were synthesized via a sol-gel method, followed by post thermal
      annealing. The effects of thermal annealing temperature and doping concentration
      on the structural and luminescent properties of Y2SiO5:Eu3+ nanocrystalline
      phosphors were systematically investigated by X-ray diffraction, scanning
      electron microscopy, transmission electron microscopy, and photoluminescence
      measurements. The nanocrystalline phosphors with a high crystallinity were
      obtained at an annealing temperature of 1300 degrees C. The luminescent spectra
      were affected strongly by the Eu3+ ion concentration and annealing temperature.
      The Eu3+ ion concentration was optimized at 5 mol%, exhibiting excellent red
      emission (-612 nm) corresponding to the 5D0 --> 7F2 transition of Eu3+ ions at
      the excitation wavelengths of 262 and 396 nm. For the optimized Y2SiO5:Eu3+
      nanocrystalline phosphors, the lifetimes were also estimated from the decay
      curves under the ultraviolet excitations.

PMID- 23858836
TI  - Solvothermal fabrication of rubidium tungsten bronze for the absorption of near
      infrared light.
AB  - For fabricating the crystal of Rb(x)WO3, the solvothermal process was performed
      using a mixed medium of water and ethanol as solvent. It has been found that the
      morphological evolutions of samples were greatly changed as disordered
      nanoparticles, bundle of nanorods and microfibers with increasing content of
      water in the starting solution. Among them, sample synthesized with assistance of
      3 ml water consisted of the nanorods with a diameter in the range of 80-150 nm,
      showing suitable size and morphology as near-infrared shielding material. On the
      merits of this nanostructure, the thin film of the Rb(x)WO3 nanorods realized
      excellent shielding of near-infrared light, meanwhile, it selectively transmitted
      the major part of visible light.

PMID- 23858837
TI  - Adsorption studies of cationic, anionic and azo-dyes via monodispersed Fe3O4
      nanoparticles.
AB  - The present paper reports the applicability of magnetite (Fe3O4) nanoparticles as
      an adsorbent for the removal of three dyes viz. Acridine orange (cationic dye),
      Comassie Brilliant Blue R-250 (anionic dye) and Congo red (azo dye) from their
      aqueous solution. The Fe3O4 nanoparticles were synthesized via simple chemical
      precipitation method using CTAB, as surfactant. The as-prepared nanoparticles
      were characterized in terms of their morphological, structural and optical
      properties by using transmission electron microscopy X-ray diffraction and UV
      visible spectroscopic measurements. The dye removal efficiency of Fe3O4 NPs have
      been determined by investigating several factors such as effect of pH, amount of
      adsorbent dose and effect of contact time on different dye concentrations.
      Langmuir and Freundlich adsorption isotherms have also been studied to explain
      the interaction of dyes. The experimental data indicate that the adsorption rate
      follows pseudo- second-order kinetics for the removal of all the three dyes.
      Moreover, the nanoparticles and the adsorbed dyes were desorbed. The identities
      of recovered nanoparticles as well as the three dyes have been found, as same and
      were reused.

PMID- 23858838
TI  - The effect of high pressure torsion on structural refinement and mechanical
      properties of an austenitic stainless steel.
AB  - In the present study, the high pressure torsion (HPT) was used to refine the
      grain structure down to the nanometer scale in an austenitic stainless steel. The
      principles of HPT lay on torsional deformation under simultaneous high pressure
      of the specimen, which results in substantial reduction in the grain size. Disks
      of the 316LVM austenitic stainless steel of 10 mm in diameter were subjected to
      equivalent strains epsilon of 32 at RT and 450 degrees C under the pressure of 4
      GPa. Furthermore, two-stage HPT processes, i.e., deformation at room temperature
      followed by deformation at 450 degrees C, were performed. The resulting
      microstructures were investigated in TEM observations. The mechanical properties
      were measured in terms of the microhardness and in tensile tests. HPT performed
      at two-stage conditions (firstly at RT next at 450 degrees C) gives similar
      values of microhardness to the ones obtained after deforming only at 450 degrees
      C but performed to higher values of the overall equivalent strain epsilon. The
      effect of high pressure torsion on structural refinement and mechanical
      properties of an austenitic stainless steel was evaluated.

PMID- 23858839
TI  - Synthesis of copper nanoparticles with controlled sizes by reverse micelle
      method.
AB  - Copper (Cu) nanoparticles with controllable sizes were successfully synthesized
      by using a modified reverse micelle method, in which copper(II) acetate was
      reacted with L-ascorbic acid in a solution containing water and xylene in the
      presence of oleic acid and oleylamine as surfactants. The as-synthesized Cu
      nanoparticles had a nearly spherical profile and multiple-twinned structures,
      whose surface was enclosed by {111} facets. Our synthetic procedure provides a
      simple and readily scalable route to the preparation of Cu nanoparticles with
      controllable sizes.

PMID- 23858840
TI  - Design issues for lateral double-diffused metal-oxide-semiconductor with higher
      breakdown voltage.
AB  - In this paper, we discuss a new High-Side nLDMOSFET whose breakdown voltage is
      over 100 V while meeting the thermal budget for the conventional process. The
      proposed n-channel lateral double-diffused metal-oxide-semiconductor field-effect
      transistor (LDMOSFET) has a feature in that the structure comprises a gap of 5
      microm between the DEEP N-WELL and the center of the source, the surface of which
      is implanted by the NADJUST-layer for high breakdown voltage and simultaneously
      the low specific on-resistance. The computer simulation of the proposed High-Side
      nLDMOS exhibits BVdss of 126 V and R(ON,sp) of as low as 2.50 m(omega) x cm2. The
      NBL, which plays a significant role as a blocking layer against the punch-through
      seems to function as a hurdle for increasing the breakdown voltage.

PMID- 23858841
TI  - Memristor-based programmable logic array (PLA) and analysis as Memristive
      networks.
AB  - A Memristor theorized by Chua in 1971 has the potential to dramatically influence
      the way electronic circuits are designed. It is a two terminal device whose
      resistance state is based on the history of charge flow brought about as the
      result of the voltage being applied across its terminals and hence can be thought
      of as a special case of a reconfigurable resistor. Nanoscale devices using dense
      and regular fabrics such as Memristor cross-bar is promising new architecture for
      System-on-Chip (SoC) implementations in terms of not only the integration density
      that the technology can offer but also both improved performance and reduced
      power dissipation. Memristor has the capacity to switch between high and low
      resistance states in a cross-bar circuit configuration. The cross-bars are formed
      from an array of vertical conductive nano-wires cross a second array of
      horizontal conductive wires. Memristors are realized at the intersection of the
      two wires in the array through appropriate processing technology such that any
      particular wire in the vertical array can be connected to a wire in the
      horizontal array by switching the resistance of a particular intersection to a
      low state while other cross-points remain in a high resistance state. However the
      approach introduces a number of challenges. The lack of voltage gain prevents
      logic being cascaded and voltage level degradation affects robustness of the
      operation. Moreover the cross-bars introduce sneak current paths when two or more
      cross points are connected through the switched Memristor. In this paper, we
      propose Memristor-based programmable logic array (PLA) architecture and develop
      an analytical model to analyze the logic level on the memristive networks. The
      proposed PLA architecture has 12 inputs maximum and can be cascaded for more
      input variables with R(off)/R(on) ratio in the range from 55 to 160 of
      Memristors.

PMID- 23858842
TI  - Sustain and address discharge characteristics of AC-PDP with MgO surface coated
      by MgO nano crystal powders.
AB  - This paper examined the sustain and address discharge characteristics of ac-PDPs
      with MgO surface coated by MgO nano crystal powders. The MgO nano crystal powder
      was deposited by about 5% on the MgO surface by using the spray method. To
      investigate the effects of the partial addition of MgO nano crystal powders on
      the sustain discharge as well as the address discharge, the luminance, IR spectra
      of 823, 828 nm, cathodoluminance, and firing voltage were measured with the
      measurement of the address delay times and wall voltage variation in the 42-inch
      ac-PDP module with a high Xe content of 17%. As a result, the statistical delay
      characteristics were improved considerably especially under the low panel
      temperature of -5 degrees C for the MgO surface with MgO nano crystal powder.
      However, both MgO surfaces with and without the MgO nano crystal powder showed
      almost similar sustain and address discharge characteristics except the
      statistical delay characteristics.

PMID- 23858843
TI  - Synthesis and electrochemical characterization of LiMn0.6Fe0.4PO4/C cathode
      material via a modified-solid state reaction method.
AB  - LiMn0.6Fe0.4PO4/C cathode material is synthesized via a modified-solid state
      reaction method. The calcination temperature is adjusted in the range of 500-700
      degrees C for 10 h. The crystal structure, morphology, and carbon coating layer
      of the synthesized LiMn0.6Fe0.4PO4/C are analyzed using X-ray diffraction (XRD),
      scanning electron microscopy (SEM), and transmission electron microscopy (TEM),
      respectively. The electrochemical performance of LiMn0.6Fe0.4PO4/C, such as
      initial capacity, rate capability, cycling performance and EIS is also evaluated.
      The synthesized cathode material shows around 100-200 nm of primary particle size
      with no impurities. The highest initial discharge capacity of 162.1 mA h g(-1)
      and columbic efficiency of 98.5% are obtained at a heat treatment temperature of
      600 degrees C. In addition, LiMn0.6Fe0.4PO4/C active material shows the high
      capacity retention of 85% at 5 C compared to 0.2 C. It also shows the excellent
      capacity retention of 97.5% after the 50th charge/discharge.

PMID- 23858844
TI  - Comparison of graphene oxide with reduced graphene oxide as hole extraction layer
      in organic photovoltaic cells.
AB  - A comparison was performed between the use of graphene oxide (GO) and reduced
      graphene oxide (rGO) as a hole extraction layer (HEL) in organic photovoltaic
      (OPV) cells with poly(3-hexylthiophene):phenyl-C61-butyric acid methyl ester.
      Hydrazine hydrate (HYD) and the thermal method (Thermal) were adopted to change
      the GO to rGO. The GO HEL was deposited on an indium tin oxide electrode by spin
      coating, followed by the reduction process to form the rGO HELs. The success of
      the reduction processes was confirmed by X-ray diffraction, Raman spectroscopy, X
      ray photoemission spectroscopy, transmittance, and 2-point probe method. The OPV
      cell with the GO (-3 nm) HEL exhibits an increased power conversion efficiency
      (PCE) as high as 2.5% under 100 mW/cm2 illumination under air mass conditions,
      which is higher than that of the OPV cell without HEL, viz. 1.78%. However, the
      PCE of the OPV cell with rGO HEL is not high as the values of 1.8% for the HYD
      rGO and 1.9% for the Thermal-rGO. The ultraviolet photoemission spectroscopy
      results showed that the work function of GO was 4.7 eV, but those of HYD-rGO and
      Thermal-rGO were 4.2 eV and 4.5 eV, respectively. Therefore, it is considered
      that GO is adequate to extract the holes from the active layer, but HYD-rGO and
      Thermal-rGO are not appropriate to use as HELs in OPV cells from the viewpoint of
      the energy alignment.

PMID- 23858845
TI  - Electrochemical properties of Sn-substituted LiMn2O4 thin films prepared by radio
      frequency magnetron sputtering.
AB  - The LiMn2O4 and LiSn0.0125Mn1975O4 thin films were grown on Pt/Ti/SiO2/Si (100)
      substrate by RF magnetron sputtering. To obtain the structural stability and good
      cycle performance, deposition parameters, namely working pressure, sputtering gas
      ratio of Ar and O2, post-annealing temperature were established. The structure
      and surface morphology of thin films were characterized by X-ray diffraction
      (XRD) and scanning electron microscopy (SEM), respectively. The electrochemical
      properties were estimated by two electrode half-cell test with WBCS 3000
      (Wonatech, Korea) at constant current rate of 1 C-rate. The Sn substituted
      LiMn2O4 thin film deposited at 10 mtorr with mixture of argon and oxygen (Ar/O2 =
      3/1) and then annealed at 500 degrees C in O2 atmosphere showed good cycle
      performance. The Sn substituted LiMn2O4 thin films showed larger capacity of -30
      microAh/microm-cm2 and higher cyclability than LiMn2O4 thin films.

PMID- 23858846
TI  - A four-bit-per-cell program method with substrate-bias assisted hot electron
      injection for charge trap flash memory devices.
AB  - We propose a four-bit-per-cell program method using a two-step sequence with
      substrate-bias assisted hot electron (SAHE) injection into the charge trap flash
      memory devices in order to overcome the limitations of conventional four-bit
      program methods, which use channel hot electron (CHE) injection. With this
      proposed method, a localized charge injection near the junction edge with an
      acceptable read margin was clearly observed, along with a threshold voltage
      difference of 1 V between the forward and the reverse read. In addition, a multi
      level storage was easily obtained using a drain voltage step of 1 V at each level
      of the three programmed states, along with a fast program time of 1 micros.
      Finally, by using charge pumping methods, we directly observed the detailed
      information on the spatial distribution of the local threshold voltage in each
      level of the four states, for each physical bit, as a function of the program
      voltage.

PMID- 23858847
TI  - Post oxygen treatment characteristics of coke as an anode material for Li-ion
      batteries.
AB  - The effect of a oxygen treatment on the electrochemical characteristics of a soft
      carbon anode material for Li-ion batteries was investigated. After a coke
      carbonization process at 1000 degrees C in an argon atmosphere, the samples were
      treated under a flow of oxygen gas to obtain a mild oxidation effect. After this
      oxygen treatment, the coke samples exhibited an improved initial coulombic
      efficiency and cycle performance as compared to the carbonized sample. High
      resolution transmission electron microscopy revealed that the carbonized cokes
      consisted of disordered and nanosized graphene layers and the surface of the
      modified carbon was significantly changed after the treatment. The chemical state
      of the cokes was analyzed using X-ray photoelectron spectroscopy and Fourier
      transform infrared spectroscopy. The enhanced electrochemical properties of the
      surface modified cokes could be attributed to the mild oxidation effect induced
      by the oxygen treatment. The mild oxidation process could have led to the
      elimination of surface imperfections and the reinforcement of a solid electrolyte
      interphase film, which resulted in the improved electrochemical characteristics.

PMID- 23858848
TI  - Electrochemical performance of Li[Ni0.7Co0.1Mn0.2]O2 cathode materials using a co
      precipitation method.
AB  - The Li[Ni0.7Co0.1Mn0.2]O2 cathode material synthesized using a co-precipitation
      method was investigated as a function of various pH level in terms of its
      microstructure and electrochemical properties. From the XRD pattern analysis, the
      Li[Ni0.7Co0.1Mn0.2]O2 cathode material prepared in this study are found to well
      coincide with typically hexagonal alpha-NaFeO2 structure. The primary particle
      size was about 100-300 nm at all compositions while secondary particle size
      increased as pH level increased from 10.34 microm (pH 10.3) to 14 microm (pH
      12.5). The initial discharge capacity increased up to 165 mAh/g (0.1 C) at pH 11,
      and then decreased down to 144 mAh/g with further increasing pH level. The
      capacity retention of the cathode (pH 11) showed 90% at 0.2 C and 15% at 5 C
      respectively compared with the discharge capacity at 0.1 C. The capacity
      retention of the cathode (pH 10.3) performed 94% of the initial capacity after 22
      cycles at 0.5 C charge/discharge test. Therefore, it is thought to be that pH
      10.3 is optimized condition of the Li[Ni0.7Co0.1Mn0.2]O2 cathode material in this
      study because pH 10.3 shows better cycle performance than other conditions.

PMID- 23858849
TI  - Fabrication of electrospun SiC fibers web/phenol resin composites for the
      application to high thermal conducting substrate.
AB  - Polycabosilane (PCS) could be spun to form fiber web by electrospinning PCS
      solution in 30% dimethylformide (DMF)/toluene solvent at 25 kV. The electrospun
      web is stabilized at 200 degrees C for 1 hour to connect fibers by softening PCS
      webs and pyrolysed to synthesize silicon carbide (SiC) webs at 1800 degrees C.
      The pyrolysis at 1800 degrees C increased the SiC crystal size to 45 nm from 3 nm
      at 1300 degrees C. However, the pyrolysis at 1800 degrees C forms pores on the
      surface of SiC fibers due to oxygen evaporation generated during thermals curing.
      SiC/phenol composite webs could be fabricated by infiltration of phenol resin and
      hot pressing. The thermal conductivity measurement indicates that higher SiC
      fibers filler contents increase the thermal conductivity up to 1.9 W/mK for 40%
      fraction of filler contents from 0.5 W/mK for 20% fraction of filler.

PMID- 23858850
TI  - Additive effect of poly(4-vinylphenol) gate dielectric in organic thin film
      transistor at low temperature process.
AB  - We fabricated pentacene-based organic thin film transistors (OTFTs) with
      formulated poly[4-vinylphenol] (PVP) gate dielectrics. The solution of gate
      dielectrics is prepared by adding methylated poly[melamine-co-formaldehyde] (MMF)
      and photo-initiator (PI) [1-phenyl-2-hydroxy-2-methylpropane-1-one,
      Darocur1173@Ciba] to PVP By using a small amount (2.4 wt%) of PI, the cross
      linking temperature is lowered to 90 degrees C, which is lower than general
      thermal curing reaction temperature for the cross-linked PVP (> 180 degrees C).
      The hysteresis and the leakage current of the OTFTs are also decreased by adding
      the MMF and PI in the PVP gate dielectric.

PMID- 23858851
TI  - Electrical and optical properties of indium zinc oxide (IZO) thin films by
      continuous composition spread.
AB  - Indium zinc oxide (IZO) films were deposited on glass substrate at room
      temperature using off-axis RF sputtering-continuous composition spread (CCS)
      system. The full range composition of IZO films were controlled by the deposition
      rate and thickness profiles of In2O3 and ZnO target. The structural, electrical
      and optical properties of IZO thin films were measured as functions of position.
      IZO thin film had the lowest resistivity and highest carrier concentration at the
      position of 15 mm (5.02 x 10(-4) omega cm, 3.9 x 10(20)/cm3). And IZO thin film
      had high transmittance in visible region at measured all positions. This study
      has investigated to explore the new composition of IZO films using CCS system.

PMID- 23858852
TI  - Synthesis of poly(p-phenylene-vinylene) derivatives containing an oxadiazole
      pendant group and their applications to organic electronic devices.
AB  - Poly(p-phenylene vinylene) (PPV) derivatives with 2,5-diphenyl-1,3,4-oxadiazole
      diyl (OXD) as the side chain, poly[2-{4-[5-(4-(heptyloxy)phenyl)-1,3,4-oxadiazole
      2-yI]phenyl-oxy}-1,4-phenylene-vinylene] (OXH-PPV), poly[2-{4-[5-(4
      (heptyloxy)phenyl)-1,3,4-oxadia-zole-2-yl]phenyl-oxy}-1,4-phenylenevinylene-co-2
      methoxy-5-(2'-ethylhexyloxy)-p-phenylene vinylene] (OXH-PPV-co-MEH-PPV), and
      poly[2-methoxy-5-(2'-ethylhexyl-oxy)-p-phenylene vinylene] (MEH-PPV), were
      synthesized via a modified Gilch route. The electron-deficient oxadiazole moiety
      was introduced on the side chain of the polymer backbone to increase the electron
      affinity of the polymers. The electroluminescent (EL) properties of the resulting
      polymers as an active layer, were investigated by the fabrication of single-layer
      LEDs and the devices using OXH-PPV-co-MEH-PPV showed better EL properties than
      those using pure MEH-PPV. Also, to investigate the switching properties of the
      resulting polymers as an active layer, OFET devices were fabricated in a top
      contact/bottom-gate configuration. The resulting FETs exhibited typical p-channel
      characteristics, field-effect mobility of 6.5 x 10(-4) - 7.0 x 10(-5) cm2 V(-1)
      s(-1), and on-off ratio of about 10(4)-10(5).

PMID- 23858853
TI  - Analysis of flicker noise for improved data retention characteristics in silicon
      oxide-high-k-oxide-silicon flash memory using N2 implantation.
AB  - In this paper, we fabricate planar-type Silicon-Oxide-High-k-Oxide-Silicon
      (SOHOS) and the planar-type SOHOS devices with N2 implantation of 3 x 10(15) dose
      in a tunneling oxide to determine the impact of N2 implantation in the tunneling
      oxide of a memory device. The N2 implantation device has better retention
      characteristics than the device with no implantation. In order establish the
      correlation between N2 implantation and retention characteristic improvement, the
      low frequency noise (1/f noise) characteristic is investigated. The normalized
      drain current noise (S(ID)/I(D)2) level of the N2 implantation device is higher
      than that of the device with no implantation, which means that N2 implantation
      causes more trap formation near the interface. Considering that N2 implantation
      does not affect the DC transfer characteristics, such as mobility and sub
      threshold slope, this finding indicates that the increase in the 1/f noise level
      is due to oxide traps rather than to interface traps. Therefore, the retention
      characteristic improvement in the N2 implantation device can be explained by the
      generation of higher number of oxide traps and an increase in the potential
      barrier blocking the leakage path in the tunneling oxide.

PMID- 23858854
TI  - Surface plasmon-enhanced light-emission mechanism of Ag-coated ZnO/Al2O3
      core/shell nanorod structures.
AB  - Surface plasmon (SP)-enhanced light emission mechanism has been investigated for
      the Ag-coated ZnO/Al2O3 core/shell nanorods (NRs). Structural characterizations
      showed that the ZnO NRs were covered by conformal Al2O3 layer and coated by Ag
      nanoparticles (NPs). The optical studies by photoluminescence (PL) showed
      abnormal variation of PL intensity with increasing the thickness of Al2O3. For
      the Ag NPs-coated ZnO NRs without Al2O3 shell layer, the PL emission quenched due
      to direct transfer of the photo-excited electrical carriers from ZnO NRs to Ag
      NPs. With thin Al2O3 layers less than 15 nm, the PL intensity increased with
      increasing the thickness of Al2O3 layers due to weakening of the Forster-type
      energy transfer while strong SP-mediated PL emission enhancement. For thicker
      Al2O3 layers than 15 nm, however, the PL intensity decreased with increasing the
      thickness of Al2O3 layers due to weakening of SP-mediated PL emission
      enhancement.

PMID- 23858855
TI  - Pulsed DC bias effects on p-type semiconductor SrCu2O2 film deposited by RF
      magnetron sputtering.
AB  - Transparent p-type semiconducting SrCu2O2 films have been deposited by RF
      magnetron sputtering under unbalanced bipolar pulsed DC bias on low-alkali glass
      substrates in a mixed gas of 1% H2/Ar below 400 degrees C. The pulsed DC bias
      voltages to substrate were varied from 0 V to -200 V with a frequency of 350 kHz.
      The effect of pulsed DC bias on the structure and electrical and optical
      properties of SrCu2O2 films has been investigated using SEM, XRD, surface
      profiler, Hall measurements and UV-VIS spectrometer. The deposition rates of
      SrCu2O2 films under DC-pulsed bias show a maximum at -100 V bias, and decreased
      with increasing the bias voltage. XRD results of the as-deposited films under the
      bias voltage at 400 degrees C reveal SrCu2O2 polycrystalline phase, and increased
      crystallite size with increasing pulsed DC bias voltage. The SrCu2O2 films
      deposited under the pulsed-bias of -100 V exhibits the highest conductivity of
      0.08 S/cm, and over 70% of transmittance at 550 nm. It is confirmed that the
      application of pulsed DC bias in sputtering improves the crystallization, crystal
      growth, and the electrical and optical properties eventually under 400 degrees C.

PMID- 23858856
TI  - Numerical simulation of solid liquid interface behavior during continuous strip
      casting process.
AB  - A new metal-strip-casting process called continuous strip-casting (CSC) has been
      developed for making thin metal strips. A numerical simulation model to help
      understand solid-liquid interface behavior during CSC has been developed and used
      to identify the solidification morphologies of the strips and to determine the
      optimum processing conditions. In this study, we used a modified level contour
      reconstruction method (LCRM) and the sharp interface method to modify interface
      tracking, and performed a simulation analysis of the CSC process. The effects of
      process parameters such as heat-transfer coefficient and extrusion velocity on
      the behavior of the solid-liquid interface were estimated and used to improve the
      apparatus. A Sn (Tin) plate of dimensions 200 x 50 x 1 mm3 was successfully
      produced by CSC for a heat-transfer coefficient of 104 W/m2 K and an extrusion
      velocity of 0.2 m/s.

PMID- 23858857
TI  - Si-nanowire-array-based NOT-logic circuits constructed on plastic substrates
      using top-down methods.
AB  - Si-nanowire (NW)-array-based NOT-logic circuits were constructed on plastic
      substrates. The Si-NW arrays were fabricated on a Si wafer through top-down
      methods, including conventional photolithography and crystallographic wet
      etching, and transferred onto the plastic substrates. Two field-effect
      transistors were fabricated on a single Si-NW array composed of five nanowires
      aligned in parallel and connected in series to form NOT-logic circuits. The
      excellent flexibility of the fabricated device was confirmed by bending-cycling
      tests. The voltage-transfer curve of the NOT-logic circuits showed an inverting
      operation with a logic swing of -92% and voltage gain of -2.5.

PMID- 23858858
TI  - Synthesis of highly ordered mesoporous Co3O4 for gas sensing.
AB  - Highly ordered mesoporous Co3O4 nanostructures were prepared using SBA-15 silica
      as hard templates. The mesoporous structures were characterized by X-ray
      diffraction, high resolution transmission electron microscopy, and N2
      adsorption/desorption isotherm analysis. The results demonstrated that the as
      prepared mesoporous Co3O4 has an ordered P6mm symmetric mesoporous structure. The
      optical absorption properties of the mesoporous Co3O4 were investigatted by UV
      Vis spectroscopy and the results indicate that the mesoporous Co3O4 materials are
      semiconducting with direct band gaps of 2, 1.385 and 0.38 eV. The gas-sensing
      performance of the mesoporous Co3O4 was tested towards a series of typical
      solvents. They demonstrated a good sensing performance towards these vapour with
      rapid response and high sensitivity at low operating temperature.

PMID- 23858859
TI  - Analysis of annealing process on P3HT:PCBM-based polymer solar cells using
      optical and impedance spectroscopy.
AB  - Thermal annealing is a well-known process for polymer solar cells because it
      improves the device characteristics. Especially, the carrier mobility and the
      light absorption of P3HT:PCBM are significantly improved after the annealing
      process. Here, we examined the changes in the morphology of P3HT:PCBM film
      according to the annealing temperature to find the changes during the thermal
      annealing process by measuring the optical absorption and X-ray diffraction. We
      also investigated the effect of two different annealing process (pre- and post
      annealing) on the device performance of the standard polymer solar cells
      consisting of ITO/MoO3 (10 nm)/P3HT:PCBM (150 nm)/LiF (0.5 nm)/Al (100 nm) by
      measuring current density-voltage and impedance characteristics. From the
      results, we found that the improvement in terms of the power conversion
      efficiency of the post-annealed device originated from the decrease of injection
      resistance between P3HT:PCBM layer and Al electrodes.

PMID- 23858860
TI  - Memristor-MOS analog correlator for pattern recognition system.
AB  - Emergence of new materials having significant improved properties continues to
      influence the formulation of novel architectures and as such new developments
      pave the way for innovative circuits and systems such as those required in visual
      imaging and recognition systems. In this paper we introduce a novel approach for
      the design of an analog comparator suitable for pattern matching using two
      Memristors as part of both the stored image data as well as that of the input
      signal. Our proposed comparator based on Memristor-CMOS fabrication process
      generates a signal indicating similarity/dissimilarity between two pattern data
      derived from image sensor and the corresponding Memristor-based template memory.
      For convenience, we also present an overview of a simplified Memristor model and
      hence provide simulation results for comparison with that of a conventional
      analog CMOS comparator.

PMID- 23858861
TI  - Characteristics of epoxy resin/SiO2 nanocomposite insulation: effects of plasma
      surface treatment on the nanoparticles.
AB  - The present study compares the effects of two different material processing
      techniques on modifying hydrophilic SiO2 nanoparticles. In one method, the
      nanoparticles undergo plasma treatment by using a custom-developed atmospheric
      pressure non-equilibrium plasma reactor. With the other method, they undergo
      chemical treatment which grafts silane groups onto their surface and turns them
      into hydrophobic. The treated nanoparticles are then used to synthesize epoxy
      resin-based nanocomposites for electrical insulation applications. Their
      characteristics are investigated and compared with the pure epoxy resin and
      nanocomposite fabricated with unmodified nanofillers counterparts. The dispersion
      features of the nanoparticles in the epoxy resin matrix are examined through
      scanning electron microscopy (SEM) images. All samples show evidence that the
      agglomerations are smaller than 30 nm in their diameters. This indicates good
      dispersion uniformity. The Weibull plot of breakdown strength and the recorded
      partial discharge (PD) events of the epoxy resin/plasma-treated hydrophilic SiO2
      nanocomposite (ER/PTI) suggest that the plasma-treated specimen yields higher
      breakdown strength and lower PD magnitude as compared to the untreated ones. In
      contrast, surprisingly, lower breakdown strength is found for the nanocomposite
      made by the chemically treated hydrophobic particles, whereas the PD magnitude
      and PD numbers remain at a similar level as the plasma-treated ones.

PMID- 23858862
TI  - AC electrical breakdown phenomena of epoxy/layered silicate nanocomposite in
      needle-plate electrodes.
AB  - Epoxy/layered silicate nanocomposite for the insulation of heavy electric
      equipments were prepared by dispersing 1 wt% of a layered silicate into an epoxy
      matrix with a homogenizing mixer and then AC electrical treeing and breakdown
      tests were carried out. Wide-angle X-ray diffraction (WAXD) analysis and
      transmission electron microscopy (TEM) observation showed that nano-sized
      monolayers were exfoliated from a multilayered silicate in the epoxy matrix. When
      the nano-sized silicate layers were incorporated into the epoxy matrix, the
      breakdown rate in needle-plate electrode geometry was 10.6 times lowered than
      that of the neat epoxy resin under the applied electrical field of 520.9 kV/mm at
      30 degrees C, and electrical tree propagated with much more branches in the
      epoxy/layered silicate nanocomposite. These results showed that well-dispersed
      nano-sized silicate layers retarded the electrical tree growth rate. The effects
      of applied voltage and ambient temperature on the tree initiation, growth, and
      breakdown rate were also studied, and it was found that the breakdown rate was
      largely increased, as the applied voltage and ambient temperature increased.

PMID- 23858863
TI  - Electrochemical studies of molybdate-doped LiFePO4 as a cathode material in Li
      ion batteries.
AB  - The use of molybdate as a new anionic dopant that replaces phosphate in LiFePO4
      was studied. When a small amount of molybdate (0.5 mol%) was used as a dopant,
      the olivine structure was maintained, while the lattice volume increased by 0.4%.
      The expanded volume facilitates ionic transfer, because of which the capacity of
      doped LiFePO4 at high current discharge rates is higher than that of pure
      LiFePO4. The discharge value increased by 25.2% at a charge rate of 5 C when the
      material was doped with 0.5 mol% molybdate ions. The slight expansion of the
      lattice volume in the olivine structure facilitates a fast redox reaction by
      lowering the charge transfer resistance. The current values from cyclic
      voltammetry indicate that the oxidation (charge) process of the cathode material
      is more improved than the corresponding reduction (discharge) process. Increasing
      the level of doping beyond 0.5 mol% had no effect on the results. At some
      discharge rates, the discharge capacity became worse. Because molybdate is
      divalent while phosphate is trivalent, a large number of molybdate ions in the
      lattice can exert considerable stress on the structure.

PMID- 23858864
TI  - Surface characteristic of chemically converted graphene coated low carbon steel
      by electro spray coating method for polymer electrolyte membrane fuel cell
      bipolar plate.
AB  - Graphene was coated on low carbon steel (SS400) by electro spray coating method
      to improve its properties of corrosion resistance and contact resistance.
      Exfoliated graphite was made of the graphite by chemical treatment (Chemically
      Converted Graphene, CCG). CCG is distributed using dispersing agent, and low
      carbon steel was coated with diffuse graphene solution by electro spray coating
      method. The structure of the CCG was analyzed using XRD and the coating layer of
      surface was analyzed using SEM. Analysis showed that multi-layered graphite
      structure was destroyed and it was transformed in to fine layers graphene
      structure. And the result of SEM analysis on the surface and the cross section,
      graphene layer was uniformly formed with 3-5 microm thickness on the surface of
      substrate. Corrosion resistance test was applied in the corrosive solution which
      is similar to the polymer electrolyte membrane fuel cell (PEMFC) stack inside.
      And interfacial contact resistance (ICR) test was measured to simulate the
      internal operating conditions of PEMFC stack. As a result of measuring corrosion
      resistance and contact resistance, it could be confirmed that low carbon steel
      coated with CCG was revealed to be more effective in terms of its applicability
      as PEMFC bipolar plate.

PMID- 23858866
TI  - Thin film solar cells with Si nanocrystallites embedded in amorphous intrinsic
      layers by hot-wire chemical vapor deposition.
AB  - We investigated the thin film growths of hydrogenated silicon by hot-wire
      chemical vapor deposition with different flow rates of SiH4 and H2 mixture
      ambient and fabricated thin film solar cells by implementing the intrinsic layers
      to SiC/Si heterojunction p-i-n structures. The film samples showed the different
      infrared absorption spectra of 2,000 and 2,100 cm(-1), which are corresponding to
      the chemical bonds of SiH and SiH2, respectively. The a-Si:H sample with the
      relatively high silane concentration provides the absorption peak of SiH bond,
      but the microc-Si:H sample with the relatively low silane concentration provides
      the absorption peak of SiH2 bond as well as SiH bond. Furthermore, the microc
      Si:H sample showed the Raman spectral shift of 520 cm(-1) for crystalline phase
      Si bonds as well as the 480 cm(-1) for the amorphous phase Si bonds. These
      bonding structures are very consistent with the further analysis of the long
      wavelength photoconduction tail and the formation of nanocrystalline Si
      structures. The microc-Si:H thin film solar cell has the photovoltaic behavior of
      open circuit voltage similar to crystalline silicon thin film solar cell,
      indicating that microc-Si:H thin film with the mixed phase of amorphous and
      nanocrystalline structures show the carrier transportation through the channel of
      nanocrystallites.

PMID- 23858865
TI  - Structural modification of fluorene-thiophene-based copolymers for OPVs.
AB  - A series of fluorene-thiophene-based pi-conjugated copolymers, PFT2, PFT4, and
      PFT2BP, have been synthesized using the Suzuki coupling reaction. Compared to
      PFT2 and PFT2BP, PFT4 film showed clearly red-shifted UV-visible absorption and
      photoluminescence (PL) spectra with maxima at 474 and 597 nm, respectively. The
      optical and electrochemical properties of copolymers could be tuned by changing
      conjugation lengths of comonomer units from bithiophene (PFT2) to quaterthiophene
      (PFT4). Moreover, PFT4 containing quaterthiophene showed relatively lower optical
      band gap of 2.16 eV. The organic photovoltaic cells (OPVs) were fabricated using
      the copolymers as donor with a sandwich configuration of
      ITO/PEDOT:PSS/copolymer:PC71BM/LiF/Al. PFT4 showed the best device performance
      with the optimized power conversion efficiency (PCE) of 2.26% (J(SC) = 7.67
      mA/cm2, V(OC) = 0.81 V, FF = 0.36). The higher OPV performance of PFT4 can be
      explained by its relatively low energy band gap and improved UV absorption
      property.

PMID- 23858867
TI  - Optical and structural properties of Al-doped ZnO thin films by sol gel process.
AB  - Transparent conducting oxide (TCO) materials with high transmittance and good
      electrical conductivity have been attracted much attention due to the development
      of electronic display and devices such as organic light emitting diodes (OLEDs),
      and dye-sensitized solar cells (DSSCs). Aluminum doped zinc oxide thin films
      (AZO) have been well known for their use as TCO materials due to its stability,
      cost-effectiveness, good optical transmittance and electrical properties.
      Especially, AZO thin film, which have low resistivity of 2-4 x 10(-4) omega x cm
      which is similar to that of ITO films with wide band gap semiconductors. The AZO
      thin films were deposited on glass substrates by sol-gel spin-coating process. As
      a starting material, zinc acetate dihydrate (Zn(CH3COO)2 x 2H2O) and aluminum
      chloride hexahydrate (AlCl3 6H2O) were used. 2-methoxyethanol and
      monoethanolamine (MEA) were used as solvent and stabilizer, respectively. After
      deposited, the films were preheated at 300 degrees C on a hotplate and post
      heated at 650 degrees C for 1.5 hrs in the furnace. We have studied the
      structural and optical properties as a function of Al concentration (0-2.5
      mol.%).

PMID- 23858868
TI  - Structural and optical properties of ZnO nanorods on Mg0.2Zn0.8O seed layers
      grown by hydrothermal method.
AB  - ZnO nanorods were grown on the Mg0.2Zn0.8O seed layers with different thickness
      by hydrothermal method. Scanning electron microscopy (SEM), X-ray diffraction
      (XRD), and photoluminescence (PL) were carried out to investigate the effects of
      the Mg0.2Zn0.8O seed layer thickness on the structural and the optical properties
      of the ZnO nanorods. The residual stress in the Mg0.2Zn0.8O seed layers was
      depended on the thickness while the texture coefficient of the Mg0.2Zn0.8O seed
      layers was not affected significantly. The smaller full width at half maximum
      (FWHM) of the ZnO (002) diffraction and near-band-edge emission (NBE) peak and
      the larger average grain size were observed from the ZnO nanorods grown on the
      Mg0.2Zn0.8O seed layers with 5 layers (thickness of 350 nm), which indicate the
      enhancement the structural and the optical properties of the ZnO nanorods.

PMID- 23858869
TI  - Microstructures and electrochemical properties of Si-Ni-xTi alloys for anode
      materials.
AB  - The phase change due to varying content of titanium in Si-Ni-xTi alloys and its
      effect on the electrochemical behavior has been investigated. Specimens were
      prepared by melt-spinning to reduce the microstructure scale. Results showed that
      silicon particles of 50-100 nm diameter and dendrites of somewhat larger scale
      were formed in the Si-Ni-Ti alloys ribbons. The microstructure of Si70Ni15Ti15
      alloy ribbons was composed of silicon particles finely dispersed in Si7Ni4Ti4
      phase. The cycle performance was improved by the formation of TiSi2 or NiSi2
      phase at the presence of Si7Ni4Ti4 phase, either of which combined with Si7Ni4Ti4
      phase effectively accommodated the volume change of silicon particles during
      cycling. The reduced scale of silicon particles contributed to the enhanced cycle
      efficiency as well.

PMID- 23858870
TI  - Microstructures and electrochemical properties of Si-xTiNi alloys for lithium
      secondary batteries.
AB  - The rapidly solidified Si-xTiNi (x = 0.2-0.45) alloy ribbons were fabricated via
      melt spinning process. The thickness of the melt-spun ribbons was about 12.5
      microm, and the sound section was selected for the experiment. The
      microstructures of the ribbons were analyzed using XRD, FE-SEM, and HR-TEM: The
      primary silicon particles of 30 nm-100 n min diameter were finely dispersed in
      the inactive buffering matrix of Si7Ni4Ti4 phase. The charge/discharge energy
      capacity and electrochemical properties were significantly influenced by the
      relative ratio of NiTi to silicon. With increasing the total amount of Ni and Ti
      content up to 45 at%, the amount of Si7Ni4Ti4 phase increased and the cycle
      performance was improved. The Si7Ni4Ti4 phase acted as a buffer for the volume
      expansion/contraction of Si occurring during the alloying and dealloying, and it
      could prevent a significant deterioration in cycle performance of the battery.

PMID- 23858871
TI  - Co and Fe doping effect on negative temperature coefficient characteristics of
      nano-grained NiMn2O4 thick films fabricated by aerosol-deposition.
AB  - Spinel structured highly dense NiMn2O4-based (NMO) negative temperature
      coefficient (NTC) thermistor thick films were fabricated by aerosol-deposition at
      room temperature. To enhance the thermistor B constant, which represents the
      temperature sensitivity of the NMO thermistor material, Co and Co-Fe doping was
      applied. In the case of single element doping of Co, 5 mol% doped NMO showed a
      high B constant of over 5000 K, while undoped NMO showed -4000 K. By doping Fe to
      the 5 mol% Co doped NMO, the B constant was more enhanced at over 5600 K. The
      aging effect on the NTC characteristics of Co doped and Fe-Co co-doped NMO thick
      film showed very stable resistivity-time characteristics because of the highly
      dense microstructure.

PMID- 23858872
TI  - Enhanced gas sensing properties of multiple networked In2O3-core/ZnO-shell
      nanorod sensors.
AB  - The influence of the encapsulation of In2O3 nanorods with ZnO on the H2S gas
      sensing properties was studied. In2O3-core/ZnO-shell nanorods were fabricated by
      a two step process comprising the thermal evaporation of an 1:1 mixture of In2O3
      and graphite powders and the atomic layer deposition of ZnO. The core-shell
      nanorods ranged from 100 to 200 nm in diameter and were up to a few hundreds of
      micrometers in length. The thickness of the ZnO shell layer in the core-shell
      nanorod ranged from 5 to 10 nm. Multiple networked In2O3-core/ZnO-shell nanorod
      sensors showed the response of more or less 4 times higher than bare In2O3
      nanorod sensors to H2S in a concentration range of 10-100 ppm at 300 degrees C.
      The substantial improvement in the response of In2O3 nanorods to H2S gas by the
      encapsulation with ZnO can be accounted for based on the space-charge model.
      Besides the enhanced sensor response, both the response and recovery times of the
      core-shell nanorods were shorter than those of the bare-In2O3 nanorods for any
      H2S concentration, respectively.

PMID- 23858873
TI  - Characterization of planar pn heterojunction diodes constructed with Cu2O
      nanoparticle films and single ZnO nanowires.
AB  - In this study, we fabricate planar pn heterojunction diodes composed of Cu2O
      nanoparticle (NP) films and single ZnO nanowires (NWs) on SiO2 (300 nm)/Si
      substrates and investigate their characteristics in the dark and under the
      illumination of white light and 325 nm wavelength light. The diode at bias
      voltages of +/- 1 V shows rectification ratios of 10 (in the dark) and 34 (under
      the illumination of white light). On the other hand, the diode exposed to the 325
      nm wavelength light exhibits Ohmic characteristics which are associated with
      efficient photocurrent generation in both the Cu2O NP film and the single ZnO NW.

PMID- 23858874
TI  - Effect of solution combusted TiO2 nanopowder within commercial BaTiO3 dielectric
      layer on the photoelectric properties for AC powder electroluminescence devices.
AB  - A unique synthesis method was developed, which is called solution combustion
      method (SCM). TiO2 nanopowder was synthesized by this method. This SCM TiO2
      nanopowder (-35 nm) was added to the dielectric layer of AC powder
      electroluminescence (EL) device. The dielectric layer was made of commercial
      BaTiO3 powder (-1.2 microm) and binding polymer. 0, 5, 10 and 15 wt% of SCM TiO2
      nanopowder was added to the dielectric layer during fabrication of AC powder EL
      device respectively. Dielectric constant of these four kinds of dielectric layers
      was measured. The brightness and current density of AC powder EL device were also
      measured. When 10 wt% of SCM TiO2 nanopowder was added, dielectric constant and
      brightness were increased by 30% and 101% respectively. Furthermore, the current
      density was decreased by 71%. This means that the brightness was double and the
      power consumption was one third.

PMID- 23858875
TI  - Synthesis and luminescence properties of iridium complexes chelated with coumarin
      ligands.
AB  - According to a recent report, the organic light-emitting diodes (OLEDs) using the
      iridium complexes of coumarin derivatives as emissive dopants are highly
      efficient and stable. Unlike the other Ir(III) phopsphorescent dopants, these
      coumarin-based Ir(III) complexes can effectively trap and transport electrons in
      the emissive layer. We have prepared a series of phosphorescent cyclometalated
      Ir(III) complexes containing 3-(2-pyridinyl)coumarin (pc) as an ancillary ligand.
      The new heteroleptic iridium complexes, Ir(C--N)2(pc) (CAN = 2-(2,4
      difluorophenyl)pyridine (F2-ppy), 2-phenylpyridine (ppy) and 2-phenylquinoline
      (pq)) were characterized by 1H NMR and mass spectrometer. As main ligands, F2
      ppy, ppy and pq were employed, which should have the drastically different ligand
      molecular orbital energy levels. The iridium complexes showed various emission
      ranges from 560 to 610 nm, depending upon the relative energy levels of their
      main and ancillary ligands. The photoabsorption, photoluminescence and
      electroluminescence of the complexes were studied. We also investigated the
      electrochemical properties of the iridium complexes to compare the HOMO and LUMO
      energy levels of these phosphorescent materials.

PMID- 23858876
TI  - Morphological studies of SnO2 thin films fabricated by using e-beam method.
AB  - This paper studies the variations in morphology of SnO2 nanostructures thin films
      deposited by using e-beam technique with the substrate temperature, oxygen
      partial pressure and the film thickness. The e-beam conditions were optimized to
      get crystalline nanosheets of SnO2. The films of 100-700 nm thickness were
      deposited on quartz substrates at temperatures ranging from room temperature (RT)
      to 300 degrees C and oxygen partial pressure ranging from 0 to 200 sccm. The
      nanostructured films have been characterized by means of X-ray diffraction (XRD),
      field emission scanning electron microscope (FE-SEM) and Energy dispersive
      spectroscopy (EDS) measurements. XRD results show that the films deposited at RT
      and 100 degrees C were amorphous, however, for 200 degrees C and 300 degrees C,
      the films showed crystalline nature with rutile structure. Also, the
      crystallinity increased with the increase of oxygen partial pressure. FE-SEM
      images revealed that at RT and 100 degrees C of substrate temperature, the film
      consist of spherical particles, whereas, the films deposited at 200 degrees C and
      300 degrees C consist of sheet like morphology having thickness -40 nm and
      lateral dimension of 1 microm, respectively. The size of the nanosheets increased
      with the increase of substrate temperature and oxygen partial pressure due to the
      enhancement in the crystallinity of the films. A possible growth mechanism of the
      formation of SnO2 nanosheets is discussed.

PMID- 23858877
TI  - Optical and structural properties of Ag:Ta2O5 nanocomposites.
AB  - In this paper, we investigated the optical and structural properties of the
      Ag:Ta2O5 nanocomposites. The nanocomposite films were prepared by magnetron co
      sputtering of Ta2O5 with Ag chips. The transmission electron microscopy images
      clearly revealed that Ag nanoparticles were successfully produced by post-thermal
      annealing of the deposited films. The reflection spectra exhibited the surface
      plasmon resonance behavior. The photoluminescence (PL) spectra indicated that the
      Ag:Ta2O5 nanocomposites exhibited larger PL intensity than pure Ag or pure Ta2O5.
      The PL enhancement is thought to be due to the surface plasmon resonance of Ag
      nanoparticles. From the spatial intensity distributions that were obtained by
      solving Maxwell equations using the three-dimensional, finite-difference time
      domain method, we found that there was strong confinement of optical field near
      the Ag nanoparticle. This optical confinement effect makes it possible to exhibit
      the enhanced PL.

PMID- 23858878
TI  - Optimization of nano-phosphor synthesis by including sensitizer doping for
      medical X-ray imaging.
AB  - Medical radiation imaging systems employ phosphors such as CaWO4 as X-ray
      receptor materials. Unfortunately, the conversion efficiencies of these materials
      are rather low (approx. 5%). Alternatives that comprise a bulk structure have
      been fabricated from rare earth metals, but they are not efficient enough to
      produce high quality images. Nano-phosphors do not suffer from the limitations
      inherent to the bulk structures of conventional phosphors. We examined the
      effects of sensitizer doping conditions on the optical characteristics and
      morphology of the rare earth phosphor Gd2O3:Eu to fabricate a novel type of nano
      phosphor. We optimized a temperature solution-combustion procedure for producing
      phosphors doped with 5 wt% Eu. Scanning electron microscopy images showed that
      the phosphors were 20-30 nm in diameter and X-ray diffraction analysis revealed
      that they underwent polycrystalline growth upon the addition of a sensitizer,
      similar to the polycrystalline growth of bulk phosphors. In addition, the
      phosphors exhibited a strong peak at 613 nm and luminescence similar to
      conventional phosphors. Phosphors that were produced using citric acid as a
      sensitizer showed more than double the level of luminescence and could be used to
      produce higher quality images compared to non-sensitized phosphors. The phosphors
      also exhibited a high degree of luminescence stability.

PMID- 23858879
TI  - Fabrication and electrochemical properties of hemisphere structured 3D
      Li(Li0.2Mn0.54Co0.13Ni0.13)O2 cathode thin film for all-solid-state lithium
      battery.
AB  - The Li[Li0.2Mn0.54Ni0.13Co0.13]O2 cathode thin films were deposited on planar,
      hemisphere, linked hemisphere, and isolated hemisphere structured Pt current
      collector thin films to investigate the effect of 3-dimensional (3-D) structure
      for the electrochemical properties of active cathode thin films. The films of
      linked hemisphere structure shows the highest initial discharge capacity of 140
      microA h/cm2-microm which is better than those of planar (62 microA h/cm2
      microm), hemisphere (94.6 microA h/cm2-microm), and isolated hemisphere (135
      microA h/cm2-microm) films due to increase of surface area for cathode thin
      films. Linked hemisphere shows the biggest capacity and the best retention rate
      because 6 nanobridges of each hemisphere bring strong connection.

PMID- 23858880
TI  - Investigation of space charge distribution of low-density polyethylene/GO-GNF
      (graphene oxide from graphite nanofiber) nanocomposite for HVDC application.
AB  - This paper reported a research on space charge distribution in low-density
      polyethylene (LDPE) nanocomposites with different types of graphene and graphene
      oxide (GO) at low filler content (0.05 wt%) under high DC electric field. Effect
      of addition of graphene oxide or graphene, its dispersion in LDPE polymer matrix
      on the ability to suppress space charge generation will be investigated and
      compared with MgO/LDPE nanocomposite at the same filler concentration. At an
      applied electric field of 80 kV/mm, a positive packet-like charge was observed in
      both neat LDPE, MgO/LDPE, and graphene/LDPE nanocomposites, whereas only little
      homogenous space charge was observed in GO/LDPE nanocomposites, especially with
      GO synthesized from graphite nano fiber (GNF) which is only -100 nm in diameter.
      Our research also suggests that dispersion of graphene oxide particles on the
      polymer matrix plays a significant role to the performance of nanocomposites on
      suppressing packet-like space charge. From these results, it is expected that
      nano-sized GO synthesized from GNF can be a promising filler material to LDPE
      composite for HVDC applications.

PMID- 23858881
TI  - Enhanced electrochromic coloration of poly(3-hexylthiophene) films by
      electrodeposited Au nanoparticles.
AB  - Au nanoparticles and poly(3-hexylthiophene) (P3HT) composite films were prepared
      by electrodeposition of Au nanoparticles using pulse-current electrodeposition
      followed by the spin coating of P3HT and their enhanced electrochromic coloration
      was investigated. A relatively uniformed Au nanoparticle was obtained by the
      controlled electrodeposition on indium tin oxide (ITO) substrate and plasmon
      absorption band of Au nanoparticles were observed. Optical and electrochemical
      properties of Au/P3HT composite films were compared with the pure P3HT films. The
      enhanced electrochromic absorption of the composite films was observed due to the
      surface plasmon resonance of the Au nanoparticles.

PMID- 23858882
TI  - Synthesis and characterization of novel soluble fulleropyrrolidine derivatives
      and their photovoltaic performance.
AB  - Currently, [60] fullerene derivatives are the focus of considerable research due
      to their important roles in many fields, especially material science. In this
      study, we synthesized the following two novel fulleropyrrolidine derivatives: C60
      fused N-methyl-(4-hexyloxybenzen-2-yl) pyrrolidine, (p-HOPF) and C60-fused N
      methyl-(2-hexyloxybenzen-2-yl) pyrrolidine, (o-HOPF). Structural assignments of
      the two fullerene derivatives were made through 1H NMR and FAB-MS. We also
      measured the optical and electrochemical properties of p-HOPF and o-HOPF through
      UV/Vis spectrophotometry and cyclic voltammetry. We found that the difference in
      the position of the alkoxyl substituent on the phenyl ring greatly affects the
      characteristics of the molecules. In particular, from the 1H NMR spectrum, we
      found that the hydrogen atoms on the carbons adjacent to the oxygens in p-HOPF
      and o-HOPF have completely different chemical environments. In order to study the
      effects of the substituent group positions on photovoltaic performance,
      photovoltaic devices were fabricated. The highest power conversion efficiency,
      0.71%, was achieved when using o-HOPF as the electron acceptor.

PMID- 23858883
TI  - On the nature of various growth facets at the interfaces of gold catalyzed
      silicon nanowires.
AB  - Modified embedded atom method-molecular dynamics simulations have been performed
      to define the various growth facets at the interfaces of Au catalyzed-silicon
      nanowires (SiNWs). The interfacial growth facet of Au/SiNW on c-Si (111) surface
      has a single, planar interface, that grows parallel to the Si (111) planes. The
      interfacial growth facet on c-Si (211) surface has an asymmetrical, cone shape.
      The interface of Au/SiNW consists of two planes--the greater being {111} and the
      lesser being {100} planes. And finally the interfacial growth facet on c-Si (110)
      surface has a symmetrical, cone shape. The interface consists of two {111}
      planes. These findings exhibit good agreement with the previous experimental
      observation done with cross-sectional high-resolution transmission electron
      microscopy. We also predict the interfacial growth facet of Au/SiNW with NW
      direction (100), explaining that such a direction rarely exists due to
      geometrical limitations. We propose that changes in SiNW direction are caused the
      existence of various growth facets at the Au/SiNW interfaces.

PMID- 23858884
TI  - The influence of surface-activated bonding treatment on the peel strength of Cu
      Ni metal clad.
AB  - Three different conditions of surface activation bonding, 0.5 m/min, 1.0 m/min
      and 1.5 m/min surface activation treatment speed, on copper and nickel substrate
      were investigated from the view point of adhesion of Cu-Ni clad metal. The
      specimen treated with surface activation treatment speed 1.0 m/min (Sample B) had
      higher peel strength properties than 0.5 m/min (Sample A) which has more long
      plasma treatment time. Observing the interface of clad with TEM and XPS spectra,
      sample B has relatively thin oxide interface including Cu2O and sample A has
      thick oxide interface including CuO. From these result, it is suggested that the
      better adhesion of Cu-Ni clad on the SAB process is not due to the increase of
      plasma treatment exposure time but due more to the control of forming condition
      as much as thin Cu2O layer growing epitaxial form.

PMID- 23858885
TI  - TiO2-nanotube-based dye-sensitized solar cells containing fluorescent material.
AB  - We fabricated a dye-sensitized solar cells (DSCs) with TiO2 nanotube arrays
      obtained by anodization of Ti foil. Vertical structure of TiO2 nanotube arrays is
      very attractive due to a high electron transfer from dye to electrode. To improve
      the power conversion efficiency, fluorescent material, F-6377, was applied in
      TiO2-nanotube-based DSCs to use a light spectrum efficiently. Fluorescent
      material was absorbed the different wavelength of 460 nm from the light absorbed
      by N719 dye. Fluorescent material to emit the absorbed light energy provided an
      additional light for dye in DSCs and additional electrons was generated.
      Thickness of TiO2 nanotube arrays grown by anodic oxidation was 15 microm. N719
      dye and 13(-)/l(-) electrolyte were used to fabricate the DSCs. The short circuit
      current densities (J(sc)) and the power conversion efficiency in DSCs with
      fluorescent were 10.8 mA/cm2 and 2.48%, respectively. Electrochemical impedance
      spectroscopy (EIS) was observed to understand an electron transfer and life time.

PMID- 23858886
TI  - Post annealing effects on the electrical characteristics of pentacene thin film
      transistors on flexible substrates.
AB  - This work studies the effect of post annealing of pentacene on a flexible
      substrate through the examination of electrical properties and surface
      morphologies. It is confirmed that the best performance of devices is achieved
      when the post annealing temperature is 60 degrees C, since the grain size
      increases, which decrease grain boundaries caused charge transport limit. We can
      also confirmed the large threshold voltage shift of device annealed at 60 degrees
      C that means the lower trap density between channel and insulator interface. The
      device annealed at 60 degrees C exhibits a saturation mobility of 1.99 cm2/V x s,
      an on/off ratio of 1.87 x 10(4), and a subthreshold slope of 2.5 V/decade.

PMID- 23858887
TI  - Numerical simulation and fabrication of silicon sheet via spin casting.
AB  - A spin-casting process for fabricating polycrystalline silicon sheets for use as
      solar cell wafers is proposed, and the parameters that control the sheet
      thickness are investigated. A numerical study of the fluidity of molten silicon
      indicates that the formation of thin silicon sheets without a mold and via spin
      casting is feasible. The faster the rotation speed of graphite mold, the thinner
      the thickness of sheet. After the spread of the molten silicon to cover the
      graphite mold with rotation speed of above 500 rpm, the solidification has to
      start. Silicon sheets can be produced by using the centrifugal force under
      appropriate experimental conditions. The spin-cast sheet had a vertical columnar
      microstructure due to the normal heat extraction to the substrate, and the sheet
      lifetime varied from 0.1 microS to 0.3 microS measured by using the microwave
      photoconductance decay (MW-PCD) to confirm that the spin-cast silicon sheet is
      applicable to photovoltaics.

PMID- 23858888
TI  - The optical properties of quantum transition on ZnS and Ge of electron
      piezoelectric interaction system under two circularly oscillating fields.
AB  - We study optical quantum transition line shapes (QTRSs) and optical quantum
      transition line widths (QTLWs) in relation to magnetic-field dependence
      properties of the electron-piezoelec potential phonon interaction system. We
      consider two systems-one is subject to right circularly oscillating external
      fields and the other is subject to left circularly oscillatory external fields.
      The main purpose of this work is to compare QTLSs, which indicate absorption
      power, in the two oscillating external fields. Our results indicate that the
      QTLSs of right circularly oscillating external fields is larger than the QTLSs of
      left circularly oscillating external fields, while the opposite result is
      obtained for the QTLWs. Through the analysis of this work, we found the
      increasing properties of QTLW and QTLS of ZnS and Ge with the temperature and the
      magnetic fields. We also found the dominant scattering processes are the phonon
      emission transition process.

PMID- 23858889
TI  - A pulse-frequency modulation sensor using memristive-based inhibitory
      interconnections.
AB  - This paper proposes a programmable inhibitory interconnection network between
      pixels in an array of novel low-voltage Schmitt-trigger-based PFM sensors that
      will be of interest for future applications in memristor-based early vision
      processing. In addition, a new low-power inverter-based pulse-frequency
      modulation (PFM) design and its integration with the network is also presented.
      To ensure no change in the memristors conductance in the network, the CMOS imager
      was designed for low voltage operation. That has resulted in a significant power
      reduction, better than 60%, and a comparable linear dynamic range when compared
      to published designs in the literature. The design was performed using a 0.13 um
      Samsung Electronics standard CMOS process, using 0.75 V supply voltage.

PMID- 23858890
TI  - Structural characteristics of ternary In(x)Ga(1-x)As nanowires on Si (111) grown
      via Au-catalyzed VLS.
AB  - We have characterized the structural properties of the ternary In(x)Ga(1-x)As
      nanowires (NWs) grown on silicon (Si) substrates using metalorganic chemical
      vapor deposition (MOCVD). Au catalyzed vapor-liquid-solid (VLS) mode was used for
      the NW growth. The density of the In(x)Ga(1-x)As NW array grown under optimized
      condition exceeds 1 x 10(8)/cm2. X-ray diffraction (XRD) spectra confirm the In
      composition (x = 0.9-0.3) of the In(x)Ga(1-x)As nanowires which bandgap energy
      can cover the entire near-infrared (NIR) range. Massive stacking faults and twin
      planes were observed but no misfit dislocation was found along the NWs as
      confirmed by transmission electron microscopy (TEM). The energy-dispersive X-ray
      spectroscopy (EDS) analysis shows the gradual variation of In composition along
      the NW.

PMID- 23858891
TI  - Investigation of transfer characteristics of high performance graphene flakes.
AB  - In this article, we attempted a study on field effect transport characteristics
      of graphene flakes. These graphene flakes were exfoliated by mechanical peeling
      off technique and the electrical contacts were patterned by photo-lithographic
      method. Graphene devices have shown better transfer characteristics which was
      obtained even in low-voltage (< 5 V). Back-gated graphene transistors were
      patterned on oxidized silicon wafers. A clear n-type to p-type transition at
      Dirac point and higher electron drain-current modulation in positive back-gate
      field with current minimum (the Dirac point) were observed at V(GS) = -1.7 V. The
      carrier mobility was determined from the measured transconductance. The
      transconductance of the graphene transistors was observed as high as 18.6 microS
      with a channel length of 68 microm. A maximum electron mobility of 1870 +/- 143
      cm2/V x s and hole mobility of 1050 +/- 35 cm2/V x s were achieved at a drain
      bias 2.1 V which are comparatively higher values among reported for mechanically
      exfoliated graphene using lithographic method. The fabricated devices also
      sustained with high-current density for 40 hr in continuous operation without any
      change in device resistance, which could be applied for robust wiring
      applications.

PMID- 23858892
TI  - Flexible transparent heaters with heating films made of indium tin oxide
      nanoparticles.
AB  - In this study, flexible transparent heaters with heating films made of indium tin
      oxide (ITO) are fabricated on plastic substrates. The optical transmittance of a
      representative flexible heater is above 90% in the visible and near infrared
      regions. The steady-state temperature is determined by the bias voltage and
      reaches about 180 degrees C at a bias voltage of 50 V. The heat-generating
      properties are nearly the same before and after the application of tensile
      strain. Furthermore, the defrosting ability is demonstrated using a block of dry
      ice.

PMID- 23858893
TI  - The effect of Ni on the microstructures and electrochemical properties of Si-Ti
      base alloys for lithium secondary batteries.
AB  - This paper presents the microstructures and electrochemical properties of Si-Ti
      Ni alloys of various compositions prepared by a rapid solidification process. Si
      15Ti-(0-25 at%)Ni alloy ingots prepared by arc-melting was melt-spun to produce
      thin strip of -15 Om thickness. The Si-Ni-Ti alloy electrode were fabricated by
      mixing the active powdered materials (88 wt%) with ketjen black (4 wt%) as a
      conductive material and polyamide-imide binder (PAI, 8 wt.%) dissolved in N
      methyl-2-pyrrolidinone (NMP). Results showed that the microstructures of melt
      spun Si-Ti-Ni ribbons consist of silicon, TiSi2, Si7Ni4Ti4, and NiSi2 phases
      depending on the composition. As the content of nickel increased in silicon
      matrix, TiSi2 phase disappeared while Si7Ni4Ti4 and NiSi2 phases are generated.
      The cycle efficiency of Si65Ti15Ni20 and Si60Ti15Ni25 alloys was significantly
      improved because of the increased volume fraction of Si7Ni4Ti4 and NiSi2 phases
      and fine particulated silicon phase.

PMID- 23858894
TI  - Vertically integrated logic circuits constructed using ZnO-nanowire-based field
      effect transistors on plastic substrates.
AB  - ZnO-nanowire-based logic circuits were constructed by the vertical integration of
      multilayered field-effect transistors (FETs) on plastic substrates. ZnO nanowires
      with an average diameter of -100 nm were synthesized by thermal chemical vapor
      deposition for use as the channel material in FETs. The ZnO-based FETs exhibited
      a high I(ON)/I(OFF) of > 10(6), with the characteristic of n-type depletion
      modes. For vertically integrated logic circuits, three multilayer FETs were
      sequentially prepared. The stacked FETs were connected in series via electrodes,
      and C-PVPs were used for the layer-isolation material. The NOT and NAND gates
      exhibited large logic-swing values of -93%. These results demonstrate the
      feasibility of three dimensional flexible logic circuits.

PMID- 23858895
TI  - Perovskite phase formation of monosized lead zirconate (PbZrO3) nanoparticles
      prepared by the sono-assisted co-precipitation method.
AB  - The chemical reaction and phase evolution of perovskite lead zirconate (PbZrO3;
      PZ) nanoparticles, synthesized by the sono-assisted co-precipitation method, have
      been investigated. The nanopowders were characterized using the X-ray diffraction
      technique (XRD), Fourier transform infrared (FT-IR) spectroscopy, Raman
      spectroscopy, transmission electron microscope (TEM) and differential scanning
      calorimetry (DSC). The perovskite phase, PbZrO3, begins to form at 600 degrees C
      and was completed at 900 degrees C. During the reaction of PbZrO3, only the
      tetragonal zirconia (t-ZrO2) phase was formed as an intermediate phase with low
      temperature range. Only Raman spectroscopy can identify the intermediate
      tetragonal zirconia (t-ZrO2) phase in PbZrO3 powders during calcinations process.
      The change in amount of the t-ZrO2 phase in PbZrO3 powders was estimated from
      Raman spectra as a function of the calcination temperature. Observations by
      transmission electron microscopy revealed that the PbZrO3 powders have a uniform
      spherical shape with nanosized particles. The average size of the particles is
      about 10.60 +/- 2 nm with narrow size distribution.

PMID- 23858896
TI  - Yttrium-doped cobalt nanoferrites prepared by sol-gel combustion method and its
      characterization.
AB  - Ferrites are extremely important magnetic ceramics in the production of
      electronic components because they reduce the energy losses by the induced
      currents acting as electrical insulators. Similarly, the spinel-structured cobalt
      based ferrites are promising materials for stress, torsion sensors and energy
      storage applications (anode materials in lithium batteries, fuel cells and solar
      cells). Therefore, many studies have focused on cobalt ferrites obtained using
      conventional techniques. Different sintering conditions, types and levels of
      substitution result in different microstructures and magnetostriction
      coefficients under a wide range of preparation conditions. Despite many attempts,
      there are no specific reports on the trivalent substitution of yttrium in cobalt
      ferrite to the best of our knowledge. In the present study, yttrium-doped cobalt
      ferrite was prepared with different concentrations to identify the crystallite
      size with respect to the yttrium concentration, temperature and changes in the
      structural and electrical properties. In addition, the resistance of the
      nanostructured yttrium-doped cobalt ferrites nanopowders was analyzed. The
      resistance was increased by the addition of yttrium to cobalt ferrites.

PMID- 23858897
TI  - Photocurrent characteristics of HgTe nanoparticle films-Si nanowires
      heterojunctions made using a simple transfer-dropping method.
AB  - In this study, pn heterojunction diodes are constructed with p-type HgTe
      nanoparticle (NP) films dropped by a nanoplotter and n-type Si nanowires (NWs)
      transferred onto plastic substrates and their optoelectronic characteristics are
      investigated under the illumination of 633-nm wavelength light. The rectification
      ratio when light is irradiated on the diode is twice that in the dark. The
      photocurrent efficiency of the diode at a bias voltage of 2.5 V is determined to
      be 0.41 microA/W, which is greater than that of the transferred Si NWs.

PMID- 23858898
TI  - TiO2 effect on crystallization mechanism and physical properties of nano glass
      ceramics of MgO-Al2O3-SiO2 glass system.
AB  - The effect of TiO2 on the degree of crystallization, thermal properties and
      microstructure for MgO-Al2O3-SiO2 glass-ceramics system containing 0-13 wt% TiO2
      and 0-1.5 wt% B2O3 in which the cordierite is the main phase was studied. Using
      Kissinger and Augis-Bennett equations, the activation energy, 510 kJ/mol and
      Avrami constant, 1.8 were calculated showing the surface-oriented crystallization
      would be preferred. The alpha-cordierite phase was generated in the glass
      ceramics of containing TiO2 of 0-5.6 wt%. However, for the glass-ceramics of TiO2
      content above 7 wt%, an alpha-cordierite disappeared and micro-cordierite phase
      was formed. The glass-ceramics of no TiO2 added had spherical crystals of few
      tens nanometer size spread in the matrix. As TiO2 content increased up to 5.6
      wt%, a lump of dendrite was formed. In the glass-ceramics containing TiO2 7-13
      wt%, in which the main phase is micro-cordierite, the dendrite crystal
      disappeared and a few hundred nanometer sized crystal particles hold tightly each
      other were generated. The thermal conductivity of glass-ceramics of both a
      cordierite and micro-cordierite base decreased with TiO2 contend added. The
      thermal conductivity of glass-ceramics of 1.5 wt% TiO2 added was 3.4 W/mK which
      is 36% higher than that of glass-ceramics of no TiO2 added. The sintering
      temperature for 1.5 wt% TiO2 glass-ceramics was 965 degrees C which could be
      concluded as to apply to LTCC process for LED packaging.

PMID- 23858899
TI  - Encapsulation of TiO2 nanoparticles with poly(4-vinylpyridine) using surface
      functionalized thiol-lactam initiated radical polymerization.
AB  - A nanocomposite of TiO2 nanoparticle with an electroactive poly(4-vinylpyridine)
      (PVP) was synthesized via a simple surface thiol-lactam initiated radical
      polymerization upon grafting from protocol. This can be achieved through the
      primary modification of the TiO2 surface with a silane coupling agent leading to
      thiol functionalized TiO2 (TiO2-SH). Subsequently, a controlled radical
      polymerization of 4-vinylpyridine in the presence of TiO2-SH and butyrolactam
      afforded PVP-g-TiO2 nanocomposites. The grafting of PVP on the surface of TiO2
      was confirmed by FT-IR, TGA, XPS, EDX, TEM and SEM analyses. The UV-vis studies
      of the synthesized PVP-g-TiO2 nanocomposite demonstrated an exceptionally good
      dispersibility in organic solvents.

PMID- 23858900
TI  - Fabrication of a polymer-metal combined atomic force microscopy probe for coarse
      food surface imaging.
AB  - We fabricated a polymer-metal combined atomic force microscopy (AFM) probe by two
      steps; a polymeric resin was used at first step, and a metal-ion was used at
      second step which needs more fabricating time than the resin. At first step, we
      fabricated a cylindrical base on to a commercial cantilever. At second step, we
      fabricated a conical probe on to the fabricated cylindrical base. To make the
      conical probe composed with silver, a 0.2 M aqueous solution of silver nitrate
      (AgNO3) was used. A 50 microm length polymeric-metallic hybrid tip has been
      fabricated to observe large bio and food samples. Generally, the AFM images of
      bio/food samples show cliff-like sharp patters in vertical. However, the AFM
      image by fabricated long tip shows clear structure of each brown rice flours. As
      most of commercial tips have three-angular pyramidal, the scanned results should
      be influenced by the lateral face of the three-angular pyramid, which results in
      cliff-like images. Because the sample size is large, the side area of the sample
      was adversely affected by the pyramidal structure during imaging. This problem
      may be resolved by designing conical structure tips. As the conical structure has
      no edge, the AFM image becomes clear. The fabricated tip has conical structure,
      and a clear AFM image was achieved.

PMID- 23858901
TI  - Effect of thermal dissipation by adding graphene materials to surface coating of
      LED lighting module.
AB  - The effect of thermal dissipation by adding graphene nano-platelets to two
      different commercially available thermal dissipation coatings (ceramic coating
      and powder coating) was studied. Steady state temperatures of each points of LED
      modules was monitored in a closed system, with an integral photo detection sphere
      where there is no external air flow. Having eliminated the contributions of
      thermal conduction and air flow convection, the module with a conventional heat
      dissipation coatings showed 8-16% enhancement of thermal dissipation compared to
      that of non-coated LED module. The addition of graphene is shown to have about 3%
      additional enhancement. By analyzing thermal resistance of each component of the
      LED module, the improved thermal conductivity of the graphene added coatings
      contributes to the enhancement of slight improvement with heat dissipation.

PMID- 23858902
TI  - Study of the microstructures and lifetime of spin-cast silicon sheets for
      photovoltaics.
AB  - Silicon sheets were fabricated by a new fabricating method, spin casting with
      various rotation speeds of the graphite mold. The microstructure of spin-cast
      silicon sheets were investigated using an electron probe microanalyzer (EPMA) and
      scanning electron microscope/electron backscatter diffraction/orientation image
      micrograph, and the lifetime of the sheets was mapped using microwave
      photoconductance decay. The silicon sheets were vertically aligned, with sizes
      ranging from tens of microns to one hundred microns. The as-grown lifetime was
      measured and found to range from 0.049 micros to 0.250 micros. The ASTM number
      was plotted against the lifetime using ASTM E112 to estimate the grain size.
      Approximately half of the grain boundaries seemed electrically inactive with
      meaning of no recombination center since the grains were growth directionally,
      especially in a longitudinal aligned. It was confirmed that the lifetime of spin
      cast sheets makes them suitably applicable for photovoltaics compared to those
      produced by alternative ribbon-producing methods.

PMID- 23858903
TI  - Initial reaction of dimethylaluminum isopropoxide with hydrogen-terminated Si
      (001) surface using density functional theory.
AB  - The initial reaction of dimethylaluminum isopropoxide (Al(CH3)2OC3H7, DMAI) with
      a fully hydrogen-terminated Si (001) surface for aluminum oxide thin-film growth
      was investigated using density functional theory. Al-C and Al-O bonds of the
      adsorbed DMAI were easily broken to produce unimethylaluminum isopropoxide (
      AICH3OC3H7, UMAI) group and dimethylaluminum (-Al(CH3)2, DMA) group on the
      surface, and methane (CH4) and isopropoxide (HOC3H7) as a by-product,
      respectively, with low energy barriers in the range of 0.22-0.35 eV. UMAI and DMA
      groups further reacted with the surface to form aluminum isopropoxide (-AlOC3H7)
      and unimethylaluminum (-AICH3) groups on the surface, and CH4 and HOC3H7 as a by
      product, respectively.

PMID- 23858904
TI  - Influence of the capping agents on synthesis of Bi2Te3 nanotubes by solution
      phase reaction.
AB  - Bi2Te3 nanotubes were synthesized by first synthesizing Te nanorods and then
      alloying it with Bi(O) reduced from Bi3+ using solution-phase reaction. The
      alloying of Bi(0) and Te nanorods was enabled by the atomic diffusion on the
      interface between two metals. The morphology of Bi2Te3 crystals was greatly
      influenced depending on kind and concentration ratio of capping agents during
      solution-phase reaction. When only a trioctylphosphine oxide (TOPO) was used as a
      capping agent, the cylinder like Bi2Te3 nanotubes with diameters of 130-160 nm or
      larger were formed while the rod like Bi2Te3 nanobelts with diameters of 25-40 nm
      were formed when only poly vinyl pyrrolidone (PVP) was used. When the mixture of
      trioctylphosphine oxide and poly vinyl pyrrolidone was used, Bi2Te3 nanotubes
      with diameters of 30-80 nm were formed.

PMID- 23858905
TI  - ZnO piezoelectric fine wire gated graphene oxide field effect transistor.
AB  - Here we report the fabrication and characteristics of graphene oxide (GO) field
      effect transistor gated with piezopotential of ZnO fine wires on a flexible
      substrate. The FET device consists of GO thin film on the bottom and ZnO
      piezoelectric fine wire (PFW) on the top. In the FET device the GO serves as a
      carrier transport channel and ZnO PFW acts as a gate. When the substrate is bent,
      a piezopotential is generated in the ZnO PFW. The piezopotential created by the
      strain in the ZnO PFW was used to control the carrier transport in the GO
      channel. This device demonstrates the application of piezoelectric ZnO PFW for
      creating the gating effect on the semiconducting performance of GO film.

PMID- 23858906
TI  - Near-infrared photodetection in n-type nanocrystalline FeSi2/p-type Si
      heterojunctions.
AB  - n-Type nanocrystalline (NC) FeSi2/p-type Si heterojunctions, which were prepared
      by pulsed laser deposition, were evaluated as a near infrared photodiode. The
      built-in potential was estimated to be approximately 1.1 eV from the capacitance
      voltage measurement. These junctions showed a rectifying behavior accompanied by
      a large leakage current. The near infrared light detection performance was
      evaluated using a 1.33 microm laser in the temperature range of 77-300 K. At a
      reverse bias of -5 V, the detectivity was 5.5 x 10(7) cm Hz1/2 W(-1) at 300 K and
      it was dramatically enhanced to be 8.0 x 10(10) cm Hz1/2 W(-1) at 77 K. It was
      demonstrated that NC-FeSi2 is a new potential material applicable to NIR
      photodetectors operating at low temperatures.

PMID- 23858907
TI  - Photoluminescence studies of ZnO nanorods grown by plasma-assisted molecular beam
      epitaxy.
AB  - Metal catalyst-free ZnO nanorods were grown on PS with buffer layers grown at 450
      degrees C by plasma-assisted molecular beam epitaxy. Room temperature and
      temperature-dependent photoluminescence were carried out to investigate the
      optical properties of the ZnO nanorods with the average diameter of 120 nm and
      length of 300 nm. Three emission peaks, free excition, neutral-donor exciton, and
      free electron-to-neutral acceptor, were observed at 10 K. Huang-Rhys factor S of
      the ZnO nanorods was 0.978, which is much higher than that of ZnO thin films. The
      values of Varshni's empirical equation fitting parameters were alpha = 4 x 10(-3)
      eV/K, beta = 4.1 x 10(4) K, and E9(0) = 3.388 eV and the activation energy was
      about 96 meV.

PMID- 23858908
TI  - Effects of surface morphology of ZnO seed layers on growth of ZnO nanostructures
      prepared by hydrothermal method and annealing.
AB  - ZnO nanostructures were grown on Si (111) substrates by a hydrothermal method.
      Prior to growing the ZnO nanostructures, ZnO seed layers with different post-heat
      temperatures were prepared by a spin-coating process. Then, the ZnO
      nanostructures were annealed at 500 degrees C for 20 min under an Ar atmosphere.
      Scanning electron microscopy (SEM), X-ray diffraction (XRD), and
      photoluminescence (PL) were carried out at room temperature (RT) to investigate
      the structural and optical properties of the as-grown and annealed ZnO
      nanostructures. The surface morphologies of the seed layers changed from a smooth
      surface to a mountain chain-like structure as the post-heating temperatures
      increased. The as-grown and annealed ZnO nanostructures exhibited a strong (002)
      diffraction peak. Compared to the as-grown ZnO nanostructures, the annealed ZnO
      nanostructures exhibited significantly strong enhancement in the PL intensity
      ratio by almost a factor of 2.

PMID- 23858909
TI  - Effect of particle size of PtRu nanoparticles embedded in WO3 on
      electrocatalysis.
AB  - Size-controlled PtRu nanoparticles embedded in WO3 were prepared by simultaneous
      multigun sputtering on pure targets of Pt, Ru, and WO3. The mean diameter of the
      PtRu nanoparticles, as confirmed by high-resolution transmission electron
      microscopy, can be varied from -2.3 to -3.6 nm by varying the RF power ratio of
      PtRu and WO3. On the basis of transmission electron diffraction results for the
      PtRu nanoparticles embedded in WO3, it was confirmed that PtRu exists as an alloy
      metal phase, whereas the WO3 matrix is present as an amorphous phase. Size
      controlled PtRu/WO3 electrodes were found to exhibit unique electronic properties
      depending on their size, which affected the potential of zero total charge and
      the methanol oxidation reaction. The mass activity of PtRu/WO3 for methanol
      oxidation was determined by the interplay of the surface electronic factors at
      the metal-solution interface; the oxophilicity of the nanoparticles increased
      with decreasing particle size.

PMID- 23858910
TI  - Nanocrystal-based complementary inverters constructed on flexible plastic
      substrates.
AB  - We demonstrate a nanocrystal (NC)-based complementary inverter constructed on a
      flexible plastic substrate. The NC-based complementary inverter consists of n
      type HgSe NC- and p-type HgTe NC-based thin-film transistors (TFTs). Solid films
      on a plastic substrate obtained from HgSe and HgTe nanocrystals by thermal
      transformation are utilized as the n- and p-channel layers in these TFTs,
      respectively. The electrical properties of these component TFTs on unstrained and
      strained substrates are characterized and the performance of the inverter on the
      flexible substrate is investigated. The inverter on the unstrained substrate
      exhibits a logic gain of about 8, a logic swing of 90%, and a noise margin of 2.0
      V. The characteristics of the inverter are changed under tensile and compressive
      strains, but not very significantly. Moreover, a comparison of the electrical
      characteristics of the n- and p-channel TFTs and the inverter is made in this
      paper.

PMID- 23858911
TI  - Synthesis and characterization of hollow alpha-Fe2O3 spheres with carbon coating
      for Li-ion battery.
AB  - Carbon coated hollow alpha-Fe2O3 spheres were prepared via a facile two-step
      hydrothermal method. The appearance and crystalline structure of the samples were
      characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and
      transmission electron microscopy (TEM). The morphology showed that the hollow
      spheres were composed of well crystallized nanoparticles after the first
      hydrothermal reaction and subsequent calcinations. A thin carbon film was coated
      on each Fe2O3 nanoparticles after the second hydrothermal procedure. This carbon
      coating was probably beneficial to maintain the microstructure of the active
      material during repeatable lithiation and delithiation. Afterwards, the samples
      were assembled into half-cells to investigate the electrochemical properties. The
      electrode delivered relatively high initial discharge/charge capacities of
      1291/890 mA h g(-1) at the rate of 0.3 C. The reversible capacity maintained very
      well in a prolonged 140 cycles. The capacity retention was 89% after 70 cycles,
      and that was 81% after 140 cycles. This exceptional lithium storage property was
      probably attributed to the porous and hollow structure which allowed the
      penetration of electrolyte to the inner of the electrode, the nanoscale Fe2O3
      particles which shortened the migration pathway for lithium ion, and the carbon
      coating which kept the active materials structure intact. The attractive
      electrochemical performance suggested the carbon coated hollow Fe2O3 spheres
      would be the potential anode material for future lithium ion battery.

PMID- 23858912
TI  - Thermal annealing effects on the physical properties of styrenic pentablock
      ionomers and their electromechanical responses.
AB  - Thermal annealing effect on the physical properties of two ionic (poly((t-butyl
      styrene)-b-(ethylene-r-propylene)-b-(styrene-r-styrene sulfonate)-b-(ethylene-r
      propylene)-b-(t-butyl-styrene (SSPB) pentablock copolymers with different ion
      exchange capacities (IEC; 1.5 and 2.0 meq/g) and their electromechanical
      responses in ionic polymer-metal composite (IPMC) devices have been investigated.
      The ionic SSPB formed the microphase-separated morphology on the several tens
      nanometer scale and the selectively sulfonated styrene middle blocks formed the
      ionic channels through which ions can pass in the membrane. The thermal annealing
      at a high temperature led to the well developed interconnectivity between
      adjacent ionic channels, and thus enhanced the ion conductivity and mechanical
      strength of membranes, resulting in an actuation enhancement of the SSPB-based
      ionic actuator.

PMID- 23858913
TI  - Morphological modification of alpha-MnO2 catalyst for use in Li/air batteries.
AB  - Single crystal alpha-MnO2 nanowires and nanopowders have been successfully
      synthesized in order to facilitate a comparison of their catalytic activity for
      use in Li-air batteries. The importance of the morphological modification of the
      alpha-MnO2 catalyst for facilitating electrochemical reactions between Li and O2
      is addressed. Distinctive catalytic activity of alpha-MnO2 is observed, which is
      in line with its different morphologies. The catalytic activity significantly
      affects the reversible capacity of Li-air batteries. A high aspect ratio, large
      surface area and good dispersibility of alpha-MnO2 in the nanowire form are
      advantageous providing larger active surfaces for promoting the fundamental
      reactions in Li-air batteries. We also introduce a robustly designed air
      electrode composed of highly porous carbon and nanostructured alpha-MnO2
      catalysts, with employs a metal foam current collector to ensure sufficient air
      permeability and to maximize electronic conduction during cycles. Our suggestions
      should prove helpful in forming a basis for further investigations in developing
      advanced Li-air batteries.

PMID- 23858914
TI  - Synthesis and binding properties of arylethyne-linked porphyrin-zinc complexes
      for organic electronics applications.
AB  - Conjugated meso-alkynyl 5,15-dimesitylporphyrin metal complexes have been
      synthesized by Sonogashira coupling reaction in good yields. Alkynyl groups were
      chosen as a link at the meso positions in order to extend the pi-conjugated
      length of porphyrin rings. These synthesized porphyrin derivatives were
      characterized by 1H NMR spectroscopy and MALDI-TOF mass spectrometry. Moreover,
      UV-visible spectroscopy and fluorescence spectroscopy were also used to
      investigate their photophysical properties. It has been demonstrated that central
      metal ions as well as meso substituents on porphyrin rings affected the
      electronic absorption and emission spectra of the compounds. Spectroscopic
      results revealed that alkyne-linked porphyrin metal complexes showed higher pi
      conjugation compared with porphyrin building blocks resulting in red shifts in
      both absorption and emission spectra. Coordination properties of synthesized
      porphyrins were preliminarily investigated by UV-visible absorption and
      fluorescence emission spectroscopic titration with pyridine as axial ligand. The
      formation of porphyrin-pyridine complexes resulted in significant red shifts in
      absorption spectra and decrease of fluorescence intensity in emission spectra.
      Moreover, the 1H NMR titration experiments suggested that central metal ions play
      an important role to coordinate with pyridine and the coordination of porphyrin
      zinc(II) complex with pyridine occur in a 1:1 ratio. From these spectroscopic
      results, alkyne-linked porphyrin metal complexes offer potential applications as
      materials for optical organic nanosensors.

PMID- 23858915
TI  - Simple fabrication of antireflective silicon subwavelength structure with self
      cleaning properties.
AB  - A subwavelength structure (SWS) was formed via a simple chemical wet etching
      using a gold (Au) catalyst. Single nano-sized Au particles were fabricated by
      metallic self-aggregation. The deposition and thermal annealing of the thin
      metallic film were carried out. Thermal annealing of a thin metallic film enables
      the creation of metal nano particles by isolating them from each other by means
      of the self-aggregation of the metal. After annealing, the samples were soaked in
      an aqueous etching solution of hydrofluoric acid and hydrogen peroxide. When
      silicon (Si) was etched for 2 minutes using the Au nano particles, the
      reflectance was decreased almost 0% over the entire wavelength range from 300 to
      1300 nm due to its deep and steeply double tapered structure. When given varying
      incident angle degrees from 30 degrees to 60 degrees, the reflectance was also
      maintained at less than 3%. Following this, the etched silicon was treated with a
      plasma-polymerized fluorocarbon (PPFC) film of about 5 nm using an ICP reactor
      for surface modification. The result of this surface treatment, the contact angle
      increased significantly from 27.5 degrees to 139.3 degrees. The surface
      modification was successful and maintained almost 0% reflectance because of the
      thin film deposition.

PMID- 23858916
TI  - Material properties of the Pt electrode deposited on nafion membrane by the
      impregnation-reduction method.
AB  - Platinum nanoparticles (Pt NPs) were chemically deposited on a Nafion polymer
      electrolyte membrane by the impregnation-reduction (I-R) procedure to prepare an
      active electrode for solid electrochemical sensors. Various analysis methods such
      as SEM, EDX, XRD and cyclic voltammogram (CV) measurements were employed in order
      to characterize microstructures and electrochemical properties of the Pt layer.
      At the conditions ([Pt(NH3)4Cl2] = 10 mM, [NaBH4] = 60 mM, 50 degrees C), the
      porous Pt thin-film, consisting of sphere-like particles formed by the
      agglomeration of primary polycrystalline Pt NPs with an average crystal size of
      13-18 nm, was obtained and confirmed to have a large surface area (roughness
      factor = 267) and strong adhesion due to the formation of interfacial Pt-Nafion
      composites. The secondary globular particles were found to have an average
      diameter of 215 nm and irregular protuberances on the surface. Furthermore, this
      electrode exhibited well-resolved CV peaks for the hydrogen redox reactions in an
      acid solution, suggesting the existence of different adsorption sites and good
      electrochemical behaviors. Pt/Nafion electrodes were prepared under different
      conditions in [Pt(NH3)4Cl2], [NaBH4] and reaction temperature, and their material
      properties were discussed from the viewpoint of a Pt growth mechanism.

PMID- 23858917
TI  - A new deposition method for the preparation of Pt-Pd nanocatalysts on a nafion
      coated carbon black via the reduction of metallic precursors in a drying process.
AB  - A simple method for the synthesis of Pt-Pd nanocatalysts was developed for a
      proton-exchange membrane fuel cell (PEMFC), which was loaded on a nafion coated
      carbon black via the sequential reduction of palladium(II) bis(acetylacetonato)
      and platinum(II) bis(acetylacetonato) in a drying process. Metallic precursors
      were sublimed and reduced on a nafion coated carbon black which was spray coated
      on a gas diffusion layer (GDL) in a glass reactor of N2 atmosphere at 180 degrees
      C for various times. The morphology and distribution of the Pt and Pd
      nanoparticles were observed by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM), and we found that the loading weight,
      number density and particle size of Pt-Pd nanoparticles increased with increasing
      exposure time at 180 degrees C.

PMID- 23858918
TI  - Integrated memristor-MOS (M2) sensor for basic pattern matching applications.
AB  - This paper introduces an integrated sensor circuit based on an analog Memristor
      MOS (M2) pattern matching building block that calculates the
      similarity/dissimilarity between two analog values. A new approach for a pulse
      width modulation pixel image sensor compatible with the memristive-MOS matching
      structure is introduced allowing direct comparison between incoming and stored
      images. The pulsed-width encoded information from the pixels is forwarded to a
      matching circuitry that provides an anti-Gaussian-like comparison between the
      states of memristors. The non-volatile and multi-state memory characteristics of
      memristor, together with the related ability to be programmed at any one of the
      intermediate states between logic '1' and logic '0' brings us closer to the
      implementation of bio-machines that can eventually emulate human-like sensory
      functions.

PMID- 23858919
TI  - Study on the development of BSCCO superconducting device with a lever-type
      magnetic force measurement unit.
AB  - BiSrCaCuO superconductor with sliver oxide was prepared by thermal pyrolysis
      method to develop a superconductor device. The BiSrCaCuO superconductor with 2.0
      wt% silver oxide showed the greatest suspension. The maximum induced voltage of
      the BiSrCaCuO superconductor with 2.0 wt.% of silver oxide formed by thermal
      pyrolysis method was about 3.95 mV at 2.0 x 10(-3) T. A lever-type magnetic force
      measurement unit quantitatively well determined the distance between the
      superconductor and toroidal magnet in which an attractive and a repulsive force
      due to suspension effect acted under a complicated magnetic field. It can be used
      for optimum designing a superconductor device.

PMID- 23858920
TI  - Improved photoluminescence efficiency in UV nanopillar light emitting diode
      structures by recovery of dry etching damage.
AB  - In this study, we have fabricated 375-nm-wavelength InGaN/AlInGaN nanopillar
      light emitting diodes (LED) structures on c-plane sapphire. A uniform and highly
      vertical nanopillar structure was fabricated using self-organized Ni/SiO2 nano
      size mask by dry etching method. To minimize the dry etching damage, the samples
      were subjected to high temperature annealing with subsequent chemical passivation
      in KOH solution. Prior to annealing and passivation the UV nanopillar LEDs showed
      the photoluminescence (PL) efficiency about 2.5 times higher than conventional UV
      LED structures which is attributed to better light extraction efficiency and
      possibly some improvement of internal quantum efficiency due to partially
      relieved strain. Annealing alone further increased the PL efficiency by about 4.5
      times compared to the conventional UV LEDs, while KOH passivation led to the
      overall PL efficiency improvement by more than 7 times. Combined results of Raman
      spectroscopy and X-ray photoelectron spectroscopy (XPS) suggest that annealing
      decreases the number of lattice defects and relieves the strain in the surface
      region of the nanopillars whereas KOH treatment removes the surface oxide from
      nanopillar surface.

PMID- 23858921
TI  - Performance enhancement of polymer electrolyte membrane fuel cells by dual
      layered membrane electrode assembly structures with carbon nanotubes.
AB  - The effect of dual-layered membrane electrode assemblies (d-MEAs) on the
      performance of a polymer electrolyte membrane fuel cell (PEMFC) was investigated
      using the following characterization techniques: single cell performance test,
      electrochemical impedance spectroscopy (EIS), and cyclic voltammetry (CV). It has
      been shown that the PEMFC with d-MEAs has better cell performance than that with
      typical mono-layered MEAs (m-MEAs). In particular, the d-MEA whose inner layer is
      composed of multi-walled carbon nanotubes (MWCNTs) showed the best fuel cell
      performance. This is due to the fact that the d-MEAs with MWCNTs have the highest
      electrochemical surface area and the lowest activation polarization, as observed
      from the CV and EIS test.

PMID- 23858922
TI  - Porous LiFePO4/C microspheres as high-power cathode materials for lithium ion
      batteries.
AB  - Porous LiFePO4/C microspheres were synthesized by a novel hydrothermal reaction
      combined with high-temperature calcinations. The morphology of the prepared
      material was investigated by field-emission scanning electron microscopy. Porous
      microspheres with diameters around 1-3 microm were obtained, which consisting of
      primary LiFePO4 nanoparticles. The electrochemical performances of the as
      prepared LiFePO4 microspheres were evaluated by cyclic voltammetry,
      electrochemical impedance spectroscopy and galvanostatic charge-discharge
      cycling. The carbon coated LiFePO4 microspheres showed lower polarization, higher
      rate capability, and better cycling stability than that of pristine LiFePO4
      microspheres, indicating the potential application as the cathode material for
      high-power lithium ion batteries.

PMID- 23858923
TI  - Preparation and thermoelectric properties of Ag-dispersed Bi0.5Sb1.5Te3.
AB  - Ag-dispersed Bi0.5Sb1.5Te3 was prepared successfully by silver acetate (AgOAc)
      decomposition and hot pressing. The Ag nanoparticles were well-dispersed in the
      Bi0.5Sb1.5Te3 matrix, and acted as phonon scattering centers effectively. The
      electrical conductivity increased systematically with increasing amount of Ag
      nanoparticle dispersion, whereas it decreased with increasing temperature similar
      to metals or degenerate semiconductors. All specimens had a positive Seebeck
      coefficient, which confirmed that the electrical charge was transported mainly by
      holes. The Seebeck coefficient of Bi0.5Sb1.5Te3 decreased with increasing
      temperature but its temperature dependence was changed by Ag dispersion. The
      power factor values for Ag-dispersed Bi0.5Sb1.5Te3 increased significantly due to
      the increase in effective carrier mass and were higher over the entire
      temperature range. The decrease in lattice thermal conductivity by Ag dispersion
      overcame the increase in electronic thermal conductivity. The thermoelectric
      figure of merit was enhanced remarkably over a wide temperature range of 323-523
      K due to the high power factor and the maintenance of low thermal conductivity.

PMID- 23858924
TI  - Structural and electrical properties of NASICON type solid electrolyte nanoscaled
      glass-ceramic powder by mechanical milling for thin film batteries.
AB  - During last two decades, lithium-based glasses have been studied extensively as
      electrolytes for solid-state secondary batteries. For practical use, solid
      electrolyte must have high ionic conductivity as well as chemical, thermal and
      electrochemical stability. Recent progresses have focused on glass electrolytes
      due to advantages over crystalline solid. Glass electrolytes are generally
      classified into two types oxide glass and sulfide glass. Oxide glasses do not
      react with electrode materials and this chemical inertness is advantageous for
      cycle performances of battery. In this study, major effort has been focused on
      the improvement of the ion conductivity of nanosized LiAlTi(PO4)3 oxide
      electrolyte prepared by mechanical milling (MM) method. After heating at 1000
      degrees C the material shows good crystallinity and ionic conductivity with low
      electronic conductivity. In LiTi2(PO4)3, Ti4+ ions are partially substituted by
      Al3+ ions by heat-treatment of Li20-Al2O3-TiO2-P2O5 glasses at 1000 degrees C for
      10 h. The conductivity of this material is 1.09 x 10(-3) S/cm at room temp. The
      glass-ceramics show fast ion conduction and low E(a) value. It is suggested that
      high conductivity, easy fabrication and low cost make this glass-ceramics
      promising to be used as inorganic solid electrolyte for all-solid-state Li
      rechargeable batteries.

PMID- 23858925
TI  - Effect of SiO2-acryl nanohybrid coating layers on transparent conducting oxide
      poly(ethylene terephthalate) superstrate.
AB  - SiO2-acryl nanohybrid coating layers were produced by hybridizing acrylic resin
      and surface-modified colloidal silica (CS) nanoparticles. First, CS nanoparticles
      were modified with methyltrimethoxysilane (MTMS) and vinyltrimethoxysilane (VTMS)
      by a sol-gel process. The surface-modified CS nanoparticles were then solvent
      exchanged to be homogeneous in acrylic resin. The Hybrid materials were mixed in
      variation with the amount of surface-modified CS nanoparticles, coated with
      poly(ethylene terephthalate) (PET), then finally cured by UV light to obtain a
      hybrid coating layer. Field emission scanning electron microscopy (FE-SEM),
      particle size analysis (using a Zetasizer), and atomic force microscopy (AFM)
      were performed to determine the morphology of the hybrid thin-films.
      Thermogravimetric analysis (TGA) was used to investigate the thermal properties.
      Fourier-transform infrared (FTIR), ultraviolet-visible (UVNis) spectroscopies,
      and pencil hardness were used to obtain the details of chemical structures,
      optical properties, and hardness, respectively. The hybrid thin films had shown
      to be enhanced properties compared to their urethane acrylate prepolymer (UAP)
      coating film.

PMID- 23858926
TI  - Synthesis and electrochemical characterization of nano-sized LiMn1.5Ni0.5O4
      cathode materials for lithium-ion batteries.
AB  - Spinel LiMn1.5Ni0.5O4 materials with different morphologies were prepared by
      solid-state reaction method using nano-sized Mn-Ni-O precursor powders. The
      effect of annealing temperature on the physical properties and electrochemical
      performance of the LiMn1.5Ni0.5O4 cathode materials was investigated. As the
      annealing temperature was increased from 700 to 1000 degrees C, the particle size
      distinctly increased. The nano-sized LiMn1.5Ni0.5O4 powder obtained at 800
      degrees C exhibited a high initial discharge capacity of 130 mA h g(-1) and good
      rate capability. The LiMn1.5Ni0.5O4 material annealed at higher temperature (1000
      degrees C) exhibited good cycling stability.

PMID- 23858927
TI  - Synthesis and electrochemical performance of 0.3Li2MnO3 x 0.7LiMO2 (M = Mn, Co,
      Ni) cathode materials for Li-lon batteries.
AB  - The Mn0.720Ni0.175Co0.105(OH)2 precursor was co-precipitated by the Couette
      Taylor reactor. The 0.3Li2MnO3 x 0.7LiMn0.60Ni0.25Co0.15O2 of the high capacity
      cathode material for a Li-ion battery was synthesized according to the amount of
      lithium excess (5-20 mol.%). X-ray diffraction (XRD) and field emission-scanning
      electron microscopy (FE-SEM) were used to characterize the 0.3Li2MnO3 x 0.7Li
      Mn0.60Ni0.25Co0.15O2. Based on the XRD patterns and FE-SEM images, the 5 and 10
      mol.% lithium excess samples were observed for spinel structure. The 15 and 20
      mol.% lithium excess samples were not observed for the structure. We can conclude
      that the spinel structure was made in 0.3Li2MnO3 x 0.7LiMn0.60-Ni0.25Co0.15O2,
      due to a lack of lithium. The discharge specific capacity of 5, 10, 15, and 20
      mol.% lithium excess were measured at 216, 246, 262, and 261 mA h g(-1),
      respectively. Cyclic voltammograms show that the Li2MnO3 has a lower lithium
      influence than a spinel or layered structure. Based on these experiment results,
      we can conclude that the best Li source amount of the 0.3Li2MnO3 x 0.7LiMn0.60
      Ni0.25Co0.15O2 synthesis is a 15 mol.% excess.

PMID- 23858928
TI  - The luminescent characterization of (Sr, Ca)2SiO4:Eu2+ nanopowders synthesized by
      a co-precipitation method.
AB  - (Sr, Ca)2SiO4:Eu2+ nanopowders were prepared by a co-precipitation method, and
      then the effects of Ca2+ ions on the structural and luminescent properties were
      investigated. The pure Sr2SiO4:Eu2+ powders were perfectly composed of the beta
      phase, whereas the substitution of Ca2+ ions led to the beta --> alpha' phase
      transition. The photoluminescence spectra of Sr2SiO4:Eu2+ exhibited two
      excitation bands at around 330 and 375 nm assigned to Eu(I) and (II) sites,
      respectively, resulting in two emission bands at around 473 and 543 nm.
      Meanwhile, the dominant peak wavelengths of the emission spectra of (Sr,
      Ca)2SiO4:Eu2+ could be tuned, depending on the cation ratio of Ca2+ to Sr2+. The
      substitution of Ca2+ ions for Sr2+ ions caused the red-shift of the emission
      peaks of Sr(2-x)Ca(x)SiO4:Eu2+ powders with increasing Ca2+ content (x = 0-1.0)
      due to the increase in the crystal field strength.

PMID- 23858929
TI  - SiO(x) nanoparticles synthesized by an evaporation and condensation process using
      induction melting of silicon and gas injection.
AB  - SiO(x) nanoparticles were synthesized using a specially designed induction
      melting system equipped with a segmented graphite crucible. The graphite crucible
      with the segmented wall was the key to enhancing the evaporation rate due to the
      increase of the evaporation area and convection of the silicon melt. Injection of
      the gas mixture of oxygen (O2) and argon (Ar) on silicon (Si) melt caused the
      formation of SiO(x) nanoparticles. The evaporated SiO(x) nanoparticles were then
      cooled and condensed in a process chamber. The effects of the O2/Ar ratio in the
      injection gas on the microstructures of the SiO(x) nanoparticles were then
      investigated. Synthesized SiO(x) nanoparticles were proven to be of a homogeneous
      amorphous phase with average diameters of 30-35 nm. The microstructures were
      independent from the O2/Ar ratio of the injected gas. However, x increased from
      1.36 to 1.84 as the O2/Ar ratio increased. The purity of the synthesized
      nanoparticles was about 99.9%. SiO(x) nanoparticles could be applied as the
      active anode material in a lithium (Li) ion secondary battery.

PMID- 23858930
TI  - Enhancement of light extraction efficiency of GaN-based light-emitting diodes by
      ZnO nanorods with different sizes.
AB  - The improvement of the optical output power of GaN-based light emitting diodes
      (LEDs) was achieved by employing nano-sized flat-top hexagonal ZnO rods. ZnO
      nanorods (NRs) with the average diameters of 250, 350, and 580 nm were grown on p
      GaN top surfaces by a simple wet-chemical method at relatively low temperature
      (90 degrees C) to investigate the effect of the diameter of ZnO NRs on the light
      extraction efficiency. Consequently, the enhancement by the factor of as high as
      2.63 in the light output intensity at 20 mA for the LED with 350 nm ZnO NRs was
      demonstrated without the increase in the operation voltage compared to the
      reference LED.

PMID- 23858931
TI  - The effect of thai glutinous rice starch on the synthesis of lead zirconate
      (PbZrO3) nanofibers via the electrospinning method.
AB  - This study synthesized blended lead zirconate (PbZrO3;PZ)/poly(ethylene
      oxide)(PEO)/Glutinous rice starch (GRS) nanofibers by the electrospinning method.
      A number of parameters such as the ratio between PEO and GRS and calcination
      temperature have been studied. The as-spun PZ/PEO/GRS composite and PZ fibers
      were characterized by TG-DTA, X-ray diffraction, FT-IR and SEM, respectively. SEM
      results showed that smooth and continuous fibers were obtained at the volume
      ratio of 10:2:1, PZ/PEO/GRS. After calcination of the as-spun PZ/PEO/GRS
      composite nanofibers at 650 degrees C for 4 h, PZ nanofibers with perovskite
      structure were obtained successfully. The fibers had a uniform and smooth surface
      without grain boundaries. However, when the calcination temperature increased to
      750 degrees C and 850 degrees C, the fiber represented a necklace-like structure
      with grain boundaries arranged by grain to grain unit cell clusters.

PMID- 23858932
TI  - Hybrid composite membranes based on polyethylene separator and Al2O3
      nanoparticles for lithium-ion batteries.
AB  - A hybrid composite membrane is prepared by coating nano-sized Al2O3 powder (13
      and 50 nm) and poly(vinylidene fluoride-co-hexafluoropropene) (P(VdF-co-HFP))
      binder on both sides of polyethylene separator. The composite membrane shows
      better thermal stability and improved wettability for organic liquid electrolyte
      than polyethylene separator, due to the presence of heat-resistant Al2O3
      particles with high-surface area in the coating layer. By using the composite
      membrane, the lithium-ion cells composed of carbon anode and LiNi1/3Co1/3Mn1/3O2
      cathode are assembled and their cycling performances are evaluated. The cells
      assembled with the composite membranes are proven to have better capacity
      retention than the cell prepared with polyethylene separator, due to the enhanced
      ability to retain the electrolyte solution in the cell. The cell assembled with
      the composite membrane containing 13 nm-sized Al2O3 particles has an initial
      discharge capacity of 173.2 mA h g(-1) with good capacity retention.

PMID- 23858933
TI  - Thickness dependence of the crystallization of Au/glass ultrathin films.
AB  - The crystallization of Au/glass ultrathin films for surface plasmon resonance
      (SPR) biosensor has been studied using synchrotron X-ray scattering and field
      emission scanning electron microscope. In films thinner than 30 nm, crystallized
      Au grains with [111] preferred orientation were formed in the as-deposited
      amorphous precursor. In film with 58-nm thickness, however, Au (200) powder
      grains existed on top of the Au (111)-oriented grains near the interface. At the
      annealing temperature of 400 degrees C, the Au (200) powder grains disappeared,
      while the Au (111)-oriented grains grew further. The behavior of the surface
      morphology of Au thin films post-annealed at 400 degrees C was consistent with
      the thickness dependence of the crystallization. In a 10-nm-thick film, the Au
      (111)-oriented grains fully crystallized, and then became separated with each
      other. By increasing to 30-nm film thickness, the Au (111)-oriented grains grew
      further, coalesced into large columnar-type grains, and showed smooth surface. We
      suggest that the appropriate thickness of Au/glass thin film for SPR biosensor
      need over 30-nm-thick, considering smooth surface.

PMID- 23858934
TI  - Morphological evolution of silver nanoparticles and its effect on metal-induced
      chemical etching of silicon.
AB  - In this report, we have demonstrated the morphological evolution of the silver
      nanoparticles (AgNPs) by controlling the growth conditions and its effect on
      morphology of silicon (Si) during metal-induced electroless etching (MICE). Self
      organized AgNPs with peculiarly shape were synthesized by an electroless plating
      method in a conventional aqueous hydrofluoric acid (HF) and silver nitrate
      (AgNO3) solution. AgNP nuclei were densely created on Si wafer surface, and they
      had a strong tendency to merge and form continuous metal films with increasing
      AgNO3 concentrations. Also, we have demonstrated that the fabrication of aligned
      Si nanowire (SiNW) arrays in large area of p-Si (111) substrates by MICE in a
      mixture of HF and hydrogen peroxide (H2O2) solution. We have found that the
      morphology of the initial AgNPs and oxidant concentration (H2O2) greatly
      influence on the shape of the SiNW etching profile. The morphological results
      showed that AgNP shapes were closely related to the etching direction of SiNWs,
      that is, the spherical AgNPs preferred to move vertical to the Si substrate,
      whereas non-spherical AgNPs changed their movement to the [100] directions. In
      addition, as the etching activity was increased at higher H2O2 concentrations,
      AgNPs had a tendency to move from the original [111] direction to the
      energetically preferred [100] direction.

PMID- 23858935
TI  - Fabrication and characterization of graphene/poly(p-phenylenediamine) hybrids.
AB  - Graphene nanosheets functionalized with poly(p-phenylenediamine) (PPDA) were
      prepared via the in-situ chemical oxidative polymerization using potassium
      persulphate as a catalyst. Graphene nanosheets were previously prepared by
      chemical reduction of exfoliated graphite oxide. The structure and morphology of
      the composite material were characterized by FTIR, XPS, HRTEM, FESEM and XRD,
      while the thermal and electrical properties were measured by TGA and a four-probe
      method. FESEM and HRTEM observations indicated that the graphene sheets were
      encapsulated in the PPDA matrix. Furthermore, the nanocomposites exhibited
      improved conductivity and thermal stability as compared with pure PPDA.

PMID- 23858936
TI  - Preparation and characterization of graphene/poly(diphenylamine) composites.
AB  - Nanocomposites of graphene nanosheets and poly(diphenylamine) (graphene-PDPA)
      were synthesized via the in-situ oxidative polymerization of diphenylamine in a
      sulphuric acid medium. First, graphite oxide (GO) was prepared by oxidation of
      natural graphite using the modified Hummer's method and subsequently reduced
      using hydrazine monohydrate. The as-prepared graphene sheets were noncovalently
      grafted with PDPA using ammonium peroxydisulphate as an oxidant. During the
      polymerization, graphene sheets were homogeneously dispersed in the PDPA matrix.
      The formation of the hybrid material was confirmed by FTIR, XPS, TGA, HRTEM,
      FESEM and XRD measurements. XPS analysis revealed the removal of oxygen
      functionality from the GO surface after reduction and the bonding structure of
      the reduced hybrids. In addition, the nanocomposites showed better thermal
      properties due to the intrinsic property of the graphene sheets.

PMID- 23858937
TI  - Electro-physical properties of superconducting ceramic thick film prepared by
      partial melting method.
AB  - BiSrCaCuO superconductor thick films were prepared at several curing
      temperatures, and their electro-physical properties were determined to find an
      optimum fabrication conditions. Critical temperatures of the superconductors were
      decreased with increasing melting temperature, which was related to the amount of
      equilibrium phases of the superconducting materials with temperature. The
      critical temperature of BiSrCaCuO bulk and thick film superconductors were 107 K
      and 96 K, respectively. The variation of susceptibility of the superconductor
      thick film formed at 950 degrees C had multi-step-type curve for 70 G externally
      applied field, whereas, a superconductor thick film formed at 885 degrees C had a
      single step-type curve like a bulk BiSrCaCuO ceramic superconductor in the
      temperature-susceptibility curves. A partial melting at 865 degrees C is one of
      optimum conditions for making a superconductor thick film with a relatively
      homogeneous phase.

PMID- 23858938
TI  - Physical, electrochemical, and thermal properties of granulated natural graphite
      as anodes for Li-ion batteries.
AB  - Two different types of granulated graphites were synthesized by blending and
      kneading of natural graphite with pitch followed by sintering methods. The
      electrochemical performances of granulated graphites were investigated as anode
      materials for use in Li-ion batteries. The blending type granulated graphite
      possesses a large amount of cavities and voids, while the kneading type
      granulated graphite has a relatively compact microstructure, which is responsible
      for a high tap density. Both granulated graphites show improved the initial
      coulombic efficiencies as a result of decrease of surface area by the
      granulations. In particular, the kneading type granulated graphite exhibits an
      excellent rate-capability without significant capacity loss. In addition, the
      thermal stabilities of both granulated graphites were also improved, which could
      be attributed to the decrease of active surface area due to pitch coating.

PMID- 23858939
TI  - Preparation and characterization of gold-decorated graphite nanosheet composites.
AB  - Some composites of gold nanoparticles and graphite nanosheets were prepared by
      electrostatic interaction, and structurally and electrochemically characterized
      using X-ray diffraction, X-ray photoelectron spectroscopy, UVNis spectroscopy,
      transmission electron microscopy, and cyclic-voltammetry. Pristine graphite was
      chemically treated using aqueous acid solution, and dispersed
      inpoly(diallyldimethylammonium) chloride aqueous solution to prepare positively
      charged graphite nanosheets. The gold nanoparticles (GNPs) in this work were
      stabilized by sodium dodecyl sulfate, poly(sodium 4-styrene sulfonate), or
      poly(vinylpyrrolidone). Gold nanoparticles and graphite nanosheet composites with
      gold nanoparticles showed the characteristic surface plasmon band at -530 nm. The
      electrochemical properties of the graphite nanosheet composites with gold
      nanoparticles were studied by cyclic voltammetry, in which reduction potential
      and reduction current of gold nanoparticles were strongly dependent on the gold
      wrapped stabilizer in the composites.

PMID- 23858940
TI  - Effect of interlayer spacing on the electrochemical properties of alkali titanate
      nanotubes.
AB  - Multilayered titanate nanotubes (TNTs) has been considered as a candidate for
      lithium ion battery anode material. However, it has a problem of high
      irreversible capacity due to trapped lithium ions in the interlayer space. To
      solve this problem, an attempt to enlarge the interlayer spacing has been made in
      this work to improve intercalation characteristics of TNTs. Monoatomic ions in
      hydrothermally heat-treated TNTs were substituted to one of Li, Na and K alkali
      ions via ion-exchange process. The TNTs (200) interlayer spacing peak in XRD
      patterns showed a shift to a lower angle, indicating an enlarged interlayer
      spacing of TNTs. The Li-, Na- and K-ion exchanged TNTs exhibited an initial
      capacity of 214, 230 and 248 mA h/g at 0.1 C, respectively, in the TNTs // LiPF6
      electrolyte // Li metal coin type cell test. It was found that the enlarged
      interlayer spacing resulted in an increment in the specific capacity and rate
      capability. This increase was attributed to both the enhanced lithium ion
      diffusion and the increased number of lithium ion intercalation sites in the TNTs
      interlayers.

PMID- 23858941
TI  - Influence of electrolytes (TEABF4 and TEMABF4) on electrochemical performance of
      graphite oxide derived from needle coke.
AB  - The structure of needle coke was changed to graphite oxide structure after
      oxidation treatment with 70 wt.% of nitric acid and sodium chlorate (NaClO3), and
      the inter-layer distance of the oxidized needle coke was expanded to 6.9
      angstroms. The first charge profile of the oxidized needle coke-cell with 1.2 M
      TEMABF4/acetonitrile solution displayed that the intercalation of electrolyte
      ions into the inter-layer occurred at 1.0 V, which value is lower than 1.3 V of
      the oxidized needle coke-cell with 1.2 M TEABF4/acetonitrile solution. After
      first charge/discharge, the cell using TEMABF4 electrolyte exhibited smaller
      electrode resistance of 0.05 omega, and larger specific volume capacitance of
      25.5 F/ml at the two-electrode system in the potential range 0-2.5 V than those
      of the cell using TEABF4 electrolyte. Compared to the TEABF4 electrolyte, better
      electrochemical performance of the TEMABF4 electrolyte in the oxidized needle
      coke may be caused by the smaller cation (TEMA+) size and better ion mobility in
      the nanopores between inter-layers.

PMID- 23858942
TI  - Clinical management of thyroid nodules with indeterminate cytology: our
      institutional experience using SIAPEC cytological criteria and V600-BRAF test.
AB  - BACKGROUND: We evaluated the diagnostic accuracy of thyroid FNAC, integrated with
      V600E - BRAF mutational study. Herein, we report our experience using the SIAPEC
      cytological morphological criteria. METHODS: From September 2009 to December
      2010, we performed ultrasound-guided fine needle aspiration cytology (FNAC) on
      124 patients with clinical evidence of a thyroid nodule, classifying the results
      in five cytological categories, according to Italian Society of Pathology and
      Cytology (SIAPEC) consensus conference morphological criteria. In patients with
      indeterminate (Tir3), suggestive of malignancy (Tir4) or positive for malignancy
      specimens (Tir5), we obtained a new biopsy in order to study V600E BRAF status.
      Patients with a diagnosis of Tir2 were assessed every six months with follow-up
      in the subsequent years. Patients with cytological diagnosis of Tir3, Tir4 and
      Tir5 underwent thyroid surgical resection with histological assessment of the
      lesion. Cyto-histological correlation was evaluated. RESULTS: We obtained the
      following results: Tir2 = 103 (83.1%), Tir3 = 14 (11.3%), Tir4 = 2 (1.6%); Tir5 =
      5 (4%). B-RAF mutation was found on 1 Tir3, 1 Tir4 and 2 Tir5. Thyroidectomy was
      performed on 17 patients classified as Tir3, Tir4 and Tir5. The diagnostic
      specificity of FNB was of 94.5%, a sensitivity of 100%, a predictive value
      positive for neoplasia of 77.7 % and a predictive value of malignancy of 61.7%.
      CONCLUSIONS: Diagnostic accuracy of cytology can be improved through the study of
      mutational status of BRAF gene. These additional evaluations are well studied,
      easy to perform and could enter in the current diagnostic procedures to optimize
      clinical management of thyroid nodular disease.

PMID- 23858943
TI  - Role of biopsy in low-grade laryngeal chondrosarcoma: report of two cases.
AB  - Laryngeal chondrosarcomas are rare tumours that account for less than 1% of all
      sarcomas and originate principally from the crycoid cartilage. We report two
      cases: the former arising from thyroid cartilage in an 85-year-old male
      presenting with a palpable neck mass and hoarseness, dyspnoea and dysphagia; the
      other in a 54-year-old male with a mass growing from crycoid cartilage, who
      underwent biopsy followed by total laryngectomy. We discuss the peculiarity of
      the site of origin and the role of biopsy, the clinical presentation of the
      former case and the diagnostic and therapeutic procedures of the latter. Since it
      is a rare form of sarcoma arising in the larynx, we discuss the role of biopsy as
      a crucial although still controversial diagnostic tool.

PMID- 23858944
TI  - Uterine endometrioid adenocarcinoma with extensive pilomatrixoma-like areas. A
      case report.
AB  - Shadow cells are typical features of pilomatrixoma, although they have been
      described in other benign cutaneous tumours with characteristics of
      differentiation toward the hair matrix. The finding of extensive shadow cell
      differentiation in visceral carcinomas is otherwise unusual. We report herein a
      case of uterine adenocarcinoma with extensive pilomatrixoma-like areas in a 74
      year-old woman. The endometrial tumour showed an invasive poorly differentiated
      growth with squamous differentiation deeply extending into the myometrium
      intermixed with lobules of empty squamoid polyhedral cells with clear shadow like
      nuclei, focally exhibiting a 'ghost' appearance. The cervix, salpinges, ovaries
      and pelvic lymph nodes were free of disease and, taking all evidence into
      account, the tumour was diagnosed as poorly differentiated endometrial
      endometrioid adenocarcinoma (FIGO stage IB). The recognition of an extensive
      pilomatrixoma-like component in a high- grade endometrioid adenocarcinoma may be
      important to avoid diagnostic misinterpretation with uterine metastases of
      malignant cutaneous pilomatrical tumours, such as pilomatrix carcinomas.

PMID- 23858945
TI  - Recurrent ossifying fibroma of the maxillary sinus in an adult patient.
AB  - In some aspects, the terminology of fibro-osseous lesions of the head remain
      equivocal. The WHO classification suggested to group cemento-ossifying fibroma
      and ossifying fibroma under the term "ossifying fibroma". Based on the different
      age of onset, localization and risk of recurrence, two types have been described:
      "juvenile ossifying fibroma", with early age of onset, which needs to be treated
      with wide surgical resection due to the high risk of recurrence; and "adult
      ossifying fibroma", arising in adult patients, with low recurrence rate, properly
      treated by conservative surgery. We describe a case of an "adult ossifying
      fibroma" of a 57-year-old woman with several relapses, for whom conservative
      therapy was inadequate. We think that the "early" age of onset should not be
      included among the essential characteristics of ossifying fibroma with a high
      risk of recurrence.

PMID- 23858946
TI  - Intraparenchymal serous papillary cystadenoma of the testis: a case report.
AB  - A case is presented of a 58-year old man with a double multilocular cystic
      intratesticular tumour exhibiting the morphological features described by the WHO
      for diagnosis of a serous papillary cystadenoma of the ovary. We classified this
      tumour as the male analogue of a respective ovarian growth.

PMID- 23858947
TI  - Molecular diagnostics of pulmonary metastasis from cervical cancer.
AB  - High-risk human papillomaviruses (HPV) are largely implicated in the
      carcinogenesis of cervical carcinomas. Their role in lung carcinomas, however, is
      still unclear. We describe the case of 44-year-old female chain-smoker with
      previous HPV-related cervical cancer and a new distant tumour in the lung after
      many years. The histologic distinction between metastatic squamous cell carcinoma
      of the cervix and another primary squamous cell tumour of the lung can be
      difficult and has important clinical implications. The aim of our study was to
      investigate whether HPV was present in both the patient's cervical cancer and her
      subsequent primary lung cancer in order to appropriately plan therapy. We tested
      both the paraffin-embedded tissue of the cervical cancer and the lung cancer for
      HPV DNA using the Qiagen HPV Sign Genotyping Test, which detected HPV16-DNA in
      both tumours. The Qiagen HPV Sign Genotyping Test is a reliable method to detect
      HPV-DNA in tissue and cytological materials, thus making it possible to
      distinguish metastatic cervical carcinoma from a new primary tumour in different
      sites.

PMID- 23858948
TI  - Pure uterine lipoma.
AB  - Pure uterine lipoma is a very rare benign mesenchymal neoplasm, and only a few
      cases have been reported in the literature. This is in contrast to leiomyoma,
      which is not only the most common neoplasm of the uterus but also one of the most
      common tumours in women, estimated to occur in 20-40% of women beyond the age of
      30 years (AFIP) and more frequently affect postmenopausal women. We report the
      case of a 70-year-old woman who presented with pelvic pain and postmenopausal
      uterine bleeding. Pure uterine lipoma was diagnosed preoperatively by CT scan
      with and without contrast and confirmed postoperatively by pathological
      examination. Clinical and histological diagnosis of pure uterine lipoma with
      immunohistochemical findings are described,and the efficacy of CT in diagnosing
      this tumour is discussed.

PMID- 23858949
TI  - [Carcinoma of the exocrine pancreas: histology report].

PMID- 23858950
TI  - Detecting psychological phenomena: taking bottom-up research seriously.
AB  - For more than 50 years, psychology has been dominated by a top-down research
      strategy in which a simplistic account of the hypothetico-deductive method is
      paired with null hypothesis testing in order to test hypotheses and theories. As
      a consequence of this focus on testing, psychologists have failed to pay
      sufficient attention to a complementary, bottom-up research strategy in which
      data-to-theory research is properly pursued.This bottom-up strategy has 2 primary
      aspects: the detection of phenomena, mostly in the form of empirical
      generalizations, and the subsequent understanding of those phenomena through the
      abductive generation of explanatory theories. This article provides a
      methodologically informative account of phenomena detection with reference to
      psychology. It begins by presenting the important distinctions between data,
      phenomena, and theory. It then identifies a number of different methodological
      strategies that are used to identify empirical phenomena. Thereafter, it
      discusses aspects of the nature of science that are prompted by a consideration
      of the distinction between data, phenomena, and explanatory theory. Taken
      together, these considerations press for significant changes in the way we think
      about and practice psychological research. The adoption of these changes would
      help psychology correct a number of its major current research deficiencies.

PMID- 23858951
TI  - Maslow and the motivation hierarchy: measuring satisfaction of the needs.
AB  - For each of the 5 needs in Maslow's motivational hierarchy (physiological, safety
      security, belongingness, esteem, and self-actualization), operational definitions
      were developed from Maslow's theory of motivation. New measures were created
      based on the operational definitions (1) to assess the satisfaction of each need,
      (2) to assess their expected correlations (a) with each of the other needs and
      (b) with four social and personality measures (i.e., family support, traditional
      values, anxiety/worry, and life satisfaction), and (3) to test the ability of the
      satisfaction level of each need to statistically predict the satisfaction level
      of the next higher-level need. Psychometric tests of the scales conducted on
      questionnaire results from 386 adult respondents from the general population lent
      strong support for the validity and reliability of all 5 needs measures.
      Significant positive correlations among the scales were also found; that is, the
      more each lower-level need was satisfied, the more the next higher-level need was
      satisfied. Additionally, as predicted, family support, traditional values, and
      life satisfaction had significant positive correlations with the satisfaction of
      all 5 needs, and the anxiety/worry facet of neuroticism had significant negative
      correlations with the satisfaction of all the needs. Multiple regression analyses
      revealed that the satisfaction of each higher-level need was statistically
      predicted by the satisfaction of the need immediately below it in the hierarchy,
      as expected from Maslow's theory.

PMID- 23858952
TI  - Music, affect, method, data: reflections on the Carroll versus Kivy debate.
AB  - The comprehensive exchange between Noel Carroll and Peter Kivy, which took place
      in 2007, addressed key issues in the relationship between music and affect. More
      than in any prior philosophical debate on this topic, experimental psychologists'
      methods and data played a significant role. However, to a nontrivial extent, the
      findings-perhaps especially the dubious-were misconstrued or misused, usually
      without acknowledging the existence of contrary data-based opinion within the
      psychology of music itself. Therefore, one objective of the present article is to
      identify the specific problematic features and shed light on the broader context
      shared by the two disciplines. A complementary goal is to examine contributions
      to philosophers' transgressions by music psychologists' insufficiently
      conscientious reporting, frequent overgeneralizations, and unawareness of
      philosophers' critical arguments. Another objective is to examine the current
      status of key concepts-the relevant music, basic emotions, mood, expression,
      induction, movement and dance, and methods (including introspection and
      experimental procedures)-thus perhaps enabling the discussion of music and affect
      to proceed with fewer misunderstandings. Finally, the article moves beyond the
      initial debate and builds on a remarkable agreement of philosophical and
      psychological opinion on a key issue (the induction of non-basic emotions by
      absolute music) to reach a new conceptual ground.

PMID- 23858953
TI  - Affective modulation of attentional switching.
AB  - Affective modulation of attentional switching may have developed early in
      evolution and may therefore have primacy over other affective influences. This
      behavioral study investigated the influence of affect on attentional switching
      between emotionally neutral stimuli, whether limited-capacity control processes
      are involved, and whether attentional flexibility should be distinguished from
      attentional broadening. Experiment 1 showed that suboptimally presented happy
      faces facilitated switching from an automatized response routine, whereas angry
      faces had the opposite effect. In Experiment 2, participants with a dominant
      global (i.e., broad) or local (i.e., narrow) spatial bias switched more easily to
      the opposite bias after suboptimal happy faces than after neutral primes but less
      easily after angry faces. Affective modulation of attentional switching was
      probably incorporated during evolution in many more complex forms of information
      processing.

PMID- 23858954
TI  - Reducing false memories via context reinstatement: the roles of encoding and
      retrieval contexts.
AB  - Reinstatement of encoding strategies during recall was investigated in 3
      experiments using the Deese-Roediger-McDermott paradigm (Deese, 1959; Roediger &
      McDermott, 1995). Participants studied lists using either elaborative or rote
      rehearsal encoding strategies. At test, participants either reinstated their
      original encoding strategies or used opposing strategies to recall. In Experiment
      1, participants provided "think aloud" verbal reports during study and test, and
      elaborative encoding led to higher levels of correct recall, more instances of
      verbalizations of critical items, and lower false recall compared with rote
      encoding. Experiment 2 replicated the results of Experiment 1 without verbal
      reports. In Experiment 3, false recall was lower only after elaborative encoding
      and reinstatement of that encoding context. Results support the role of
      distinctiveness in false recall, which is sensitive to changes in list context
      and retrieval context after elaborative encoding.

PMID- 23858955
TI  - Characterizing the developmental profile of effort-induced motor overflow across
      a timed trial.
AB  - Motor overflow is overt involuntary movement that accompanies voluntary movement.
      This study investigated the change in overflow production across a timed trial
      and the factors that affected this profile. Seventeen children (aged 8-11 years),
      17 young adults (aged 18-35 years), and 17 older adults (aged 60-80 years)
      performed a 5-s finger pressing task by exerting 33% or 66% of their maximal
      force output using either index finger. Overflow was recorded as force from the
      alternative index finger. Young adult overflow remained stable over the 5 s. The
      rate of overflow increase over time was significantly greater for children than
      young adults. There was also a tendency for a greater overflow increase in older
      adults than in young adults. This overflow gradient was also greater in the right
      hand, particularly for children. These findings indicate that the neurological
      processes underlying overflow production are age dependent. Overflow progressed
      in a dynamic fashion over the course of a trial in children and older adults,
      probably because of increased bilateral cortical activation and the facilitation
      of motor task performance. This study is unique in quantitatively capturing the
      dynamic profile of overflow production in healthy participants across the life
      span.

PMID- 23858956
TI  - Cognitive processing of scrambled faces.
AB  - We propose a model, face-checking, that is based on first-order relational
      properties and discriminates between different faces (regular and scrambled) and
      predicts their similarity choice in 2 orientations: upright and inverted. The
      results of an experiment confirmed the model's predictive ability. An alternative
      hypothesis, which is based on facial configural information, failed to provide an
      efficient explanation for these findings, as the proposed model does. The model
      shows how components of first-order relational properties are mathematically
      integrated and involved in face processing.

PMID- 23858957
TI  - Fabrication of seamless electrospun collagen/PLGA conduits whose walls comprise
      highly longitudinal aligned nanofibers for nerve regeneration.
AB  - An ideal nerve scaffold should supply structural guidance and trophic support to
      facilitate nerve regeneration. Aligned electrospun nanofibers have shown
      considerable promise for the precise guidance of regenerating axons in vitro and
      in vivo. Therefore, uniaxially aligned three-dimension (3D) nanofiberous
      scaffolds may allow regenerating axons to traverse large gaps to treat severe
      nerve injuries. However, the aligned 3D conduit was always rolled by an aligned 2
      dimensional (2D) sheet in current fabrication methods, which was inconvenient for
      transplant due to the discontinuous joint and inconsistent size. We developed a
      modified one-step electrospinning technique to produce a seamless 3D nanofiberous
      nerve conduit (NC) with highly longitudinal aligned nanofibers that combines the
      biocompatibility of natural collagen and the strength of the synthetic polymer
      poly(lactic-co-glycolic acid) (PLGA). Scanning electron microscopy (SEM)
      confirmed the parallel alignment of the scaffold fibers. To test the
      effectiveness of these scaffolds at restoring neuronal connections, they were
      implanted into adult rats across a 13 mm sciatic nerve defect. Tests of, motor
      function, nerve conduction, axonal and Schwann cell morphology, and marker
      expression all revealed that uniaxially aligned seamless 3D electrospun
      collagen/PLGA NCs were superior to randomly oriented NCs and inferior to
      autografts for promoting axon regeneration, myelination, action potential
      propagation, neuromuscular transmission, and functional recovery. These
      uniaxially aligned seamless 3D electrospun collagen/PLGA nerve guides can also
      incorporate signaling molecules and additional structural cues to guide nerve
      growth, and so may be a promising substitute for autogenous nerve grafts.

PMID- 23858958
TI  - Integrated microfluidic system capable of size-specific droplet generation with
      size-dependent droplet separation.
AB  - Droplet-based microfluidics is receiving much attention in biomedical research
      area due to its advantage in uniform size droplet generation. Our previous
      results have reported that droplet size plays an important role in drug delivery
      actuated by flagellated bacteria. Recently, many research groups have been
      reported the size-dependent separation of emulsion droplets by a microfluidic
      system. In this paper, an integrated microfluidic system is proposed to produce
      and sort specificsized droplets sequentially. Operation of the system relies on
      two microfluidic transport processes: initial generation of droplets by
      hydrodynamic focusing and subsequent separation of droplets by a T-junction
      channel. The microfluidic system is fabricated by the SU-8 rapid prototyping
      method and poly-di-methyl-siloxane (PDMS) replica molding. A biodegradable
      polymer, poly-capro-lactone (PCL), is used for the droplet material. Using the
      proposed integrated microfluidic system, specific-sized droplets which can be
      delivered by flagellated bacteria are successfully generated and obtained.

PMID- 23858959
TI  - Cell uptake enhancement of folate targeted polymer coated magnetic nanoparticles.
AB  - Dual targeted drug delivery systems represent a potential platform for developing
      efficient vector to tumor sites. In this study we evaluated a folate- and
      magnetic-targeted nanocarriers based on 10 nm iron oxide nanodomais coated with
      the properly synthesized and characterized folic acid (FA)-functionalized
      amphiphilic copolymer PHEA-PLA-PEG-FA. FA was chemically conjugated to one end of
      diamino-polyethylene glycol of 2000 Da, in order to ensure its exposition on the
      polymer coated magnetic nanoparticles (MNPs-FA). The prepared nanoparticles have
      been exhaustively characterized by different methods, including DLS, SEM, FT-IR
      and magnetic measurements. Magnetic nanoparticles showed dimension of about 37 nm
      with a narrow size distribution and a characteristic superparamagnetic behaviour.
      The lack of cytotoxicity of MNPs-FA and MNPs was assessed both on MCF7 cells,
      used as a model tumor cell line, and on 16HBE, used as normal human cell model,
      by evaluating cell viability using MTS assay, while the preferential
      internalization of MNPs-FA into tumor cells rather that into normal cells was
      confirmed by the quantization of internalized iron oxide. Uptake studies were
      also performed in the presence of a permanent magnet in order to verify the
      synergistic effect of magnetic field in enhancing the internalization of magnetic
      nanoparticles. Finally, real-time confocal microscopy experiments were carried
      out to further confirmed that FA ligand enhances the MNPs-FA accumulation into
      cancer cell cytoplasm.

PMID- 23858960
TI  - Induction of apoptosis and inhibition of angiogenesis by PEGylated liposomal
      quercetin in both cisplatin-sensitive and cisplatin-resistant ovarian cancers.
AB  - The clinical efficiency of cisplatin against ovarian cancer is often limited by
      the development of drug resistance. In this work, we investigated PEGylated
      liposomal quercetin (Lipo-Que) on cisplatin-sensitive (A2780s) and cisplatin
      resistant (A2780cp) human ovarian cancer models in vitro and in vivo to reveal
      whether a cisplatin-resistant ovarian cancer has susceptibility to quercetin
      (Que) and the mechanism of its antitumor activity. Lipo-Que was prepared using a
      solid dispersion method, and the obtained Lipo-Que is monodisperse with a mean
      diameter of 163 +/-10 nm. Besides, in vitro drug release assay showed a sustained
      release behavior of Lipo-Que. In vitro experiments suggested that Lipo-Que
      inhibited cell proliferation, induced apoptosis, and induced cell cycle arrest in
      both A2780s and A2780cp cells. Furthermore, antitumor activity of Lipo-Que was
      investigated in both cisplatin-sensitive and cisplatin-resistant human ovarian
      tumor xenograft models in nude mice. Lipo-Que significantly suppressed tumor
      growth in both models in comparison with free Que, blank liposomes (Lipo), or
      normal saline (NS). Furthermore, immunohistochemistry and immunofluorescence
      tests revealed that Lipo-Que induced apoptosis, decreased microvessel density,
      and inhibited proliferation of tumors in both A2780s and A2780cp tumor models.
      Therefore, our results suggest that Lipo-Que is an effective agent to inhibit
      tumor growth in both cisplatin-sensitive and cisplatin-resistant human ovarian
      cancers.

PMID- 23858961
TI  - Water-soluble and biocompatible MnO@PVP nanoparticles for MR imaging in vitro and
      in vivo.
AB  - The uniform-sized manganese oxide nanoparticles (the oleic-capped MnO NPs) were
      synthesized by the thermal decomposition of Mn-oleate complex and were
      transferred into water with the help of cationic surfactant of cetyltrimethyl
      ammonium bromide (CTAB), then the poly(vinylpyrrolidone) (PVP) membrane was
      further coated on to them with the aid of anionic dispersant of
      poly(styrenesulfonate) (PSS) by layer-by-layer electrostatic assembly to render
      them water soluble and biocompatible. They were characterized by transmission
      electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction
      (XRD), Fourier-transform infrared (FTIR) and MTT assay. In vitro cellular uptake
      test revealed the MnO@PVP NPs were low cytotoxic, biocompatible and could be used
      as a T,-positive contrast agent for passive targeting magnetic resonance imaging
      (MRI). Interestingly, signal enhancement in cerebral spinal fluid (CSF) spaces in
      vivo experiment suggested that the MnO@PVP NPs can pass through the blood brain
      barrier (BBB). These results show that MnO@PVP NPs are good candidates as MRI
      contrast agents with the lack of cytotoxicity and have great potential
      applications in magnetic nano-device and biomagnetic field.

PMID- 23858962
TI  - Engineering bioconjugated gold nanospheres and gold nanorods as label-free
      plasmon scattering probes for ultrasensitive multiplex dark-field imaging of
      cancer cells.
AB  - In this paper, we proposed the use of gold nanoparticles as plasmon scattering
      probes for dark-field multiplex imaging of live cancer cells. By carefully
      engineering the surfaces, aqueous dispersions of anti-EGFR antibody-conjugated
      gold nanospheres and gold nanorods are prepared. We demonstrated the receptor
      mediated delivery of antibody conjugated gold nanospheres and gold nanorods into
      EGFR receptor-positive oral squamous cell carcinoma cell line by using darkfield
      microscopy technique. Our result suggests that gold nanospheres and gold nanorods
      formulations could provide up to 7 types of plasmon scattering probes based on
      their tunability range with a 100 nm spectral separation in absorption bands.

PMID- 23858963
TI  - Current stimulator IC with adaptive supply regulator for visual prostheses.
AB  - The current stimulation method is preferred over the voltage stimulation method
      in the visual prostheses based on functional electrical stimulation (FES) due to
      its accurate charge control property. Previous current stimulators are generally
      implemented using a static high supply voltage, because current stimulations
      require high output voltage compliance. This high static supply voltage, however,
      may harm the tissues or damage the electrodes. This paper proposes a novel
      integrated circuit (IC) current stimulator with adaptive supply regulator (ASR).
      In the proposed circuit, the internal power supply voltage is not static, but
      adaptively regulated to the minimum required voltage for stimulation. The current
      feedback loop in the ASR adaptively increases the internal supply voltage when
      the monitored current is smaller than the desired current, and reduces the
      internal supply voltage when the monitored current is higher than the desired
      current. With this method, the internal supply voltage of the stimulator is
      minimized, and potential damages of the tissues due to high voltage (HV)
      stimulation can be reduced. Also the current feedback loop in ASR enhances the
      accuracy of the output current and the robustness to the load impedance. The
      stimulator IC is fabricated using 0.35 micro m bipolar-CMOS-DMOS (BCDMOS)
      process, and the size of the chip is 2000 micro m by 1500 micro m.

PMID- 23858964
TI  - Nanosponges encapsulating dexamethasone for ocular delivery: formulation design,
      physicochemical characterization, safety and corneal permeability assessment.
AB  - Nanosponges (NS) were synthesized by crosslinking of beta cyclodextrins with
      diphenyl carbonate. It is a hyper-branched polymer with an ultra high
      encapsulation efficiency leading to formation of colloidal systems. Dexamethasone
      (DEX) on the other hand is a poorly soluble drug with a poor corneal
      permeability. Excessive instillation of ocular suspension of dexamethasone leads
      to various complications thereby necessitating a novel nanotherapeutic system
      with greater ocular retention and permeation. This study aimed at formulating
      complexes of DEX with three types of beta-cyclodextrin NS obtained with different
      cross-linking ratio (viz. 1:2, 1:4 and 1:8 on molar basis with the cross-linker)
      for ocular applications. Nano-encapsulation was done by incubation-lyophilization
      technique to yield various formulations of Nanosponges (viz. F1:2, FI:4 and
      F1:8). From drug loading studies it was found that DEX was loaded in the highest
      amount in (NS 1:4), as much as 10% w/w as compared to 3% w/w and 5% w/w in 1:2
      and 1:8 types of NS respectively. In vitro release studies showed that release of
      DEX was in a controlled manner for around 300 minutes. The particle sizes of the
      loaded NS formulations were between 350 and 660 nm with low polydispersity
      indices. The zeta potentials were sufficiently high (-20 to -27 mV) to obtain a
      stable colloidal nanosuspension. X-ray powder diffraction, differential scanning
      calorimetry and Fourier transform infra-red attenuated transmittance reflectance
      spectroscopy studies confirmed the interactions and encapsulation of DEX with NS.
      Transmission electron microscopy and atomic force microscopy studies confirmed
      its spherical colloidal nature. Ex vivo safety assessment done on bovine cornea
      showed no adverse reactions proving the safety of the system. Adhesion and
      retention properties of NS formulations were confirmed by use of 6-Coumarin as a
      model fluorescent marker. Corneal permeability of DEX from optimized formulations
      done on excised bovine cornea in corneal holders showed that the NS formulation
      showed higher permeability than the marketed formulation.

PMID- 23858965
TI  - Selective pathogen targeting and macrophage evading carbon nanotubes through
      dextran sulfate coating and PEGylation for photothermal theranostics.
AB  - Single-walled carbon nanotubes (SWNTs) have shown promise as in vivo contrast
      nanoagents for medical theranostics, in particular photoacoustic and photothermal
      imaging and therapy, as well as targeted drug delivery systems. However, SWNTs
      have not proved able to evade biological obstacles, such as opsonization and
      phagocytosis by macrophage and nonspecific attachments to cells and other
      biological components in the bloodstream, before reaching target tissues and
      cells in vivo. Here, we demonstrate the stealth character of dextran sulfate (DS)
      coated SWNTs (DS-SWNTs) towards human macrophages and other biological barriers
      using Staphylococcus aureus, a bacterial pathogen, as a model. DS-SWNTs were
      compared to PEGylated SWNTs, a commonly accepted standard for rendering
      nanoparticles immune to opsonization. Also a new site-specific conjugation
      strategy was developed to functionalize antibody (Ab) on DS-SWNT in an upright
      way, enhancing their targeting efficiency. DS coating was proved to be resistant
      to opsonins and bacterial cells, demonstrating its potential to provide
      considerable stealth.character to SWNTs with excellent immunity versus
      macrophages and other biological barriers, and achieve prolonged blood
      circulation times. Moreover, the hybrid nanoagents could not only selectively
      bind to target pathogenic cells upon the controlled Ab attachment but also
      effectively eradicate pathogens after near-infrared laser irradiation.

PMID- 23858966
TI  - An intrinsic therapy of gold nanoparticles in focal cerebral ischemia-reperfusion
      injury in rats.
AB  - Ischemic stroke is a leading cause of death and disability, and the treatment
      options are limited. Recent studies demonstrated that the promising applications
      of gold nanoparticles (Au-NPs) as intrinsic therapeutics; however, little is
      known about the effect of Au-NPs on cerebral ischemia-reperfusion (I/R) injury.
      In this paper, the role of Au-NPs on cerebral I/R injury in the rat middle
      cerebral artery occlusion (MCAO) model was investigated using citrate-capped 5 nm
      and 20 nm Au-NPs. It was found that 20 nm Au-NPs administration led to remarkable
      amelioration of neurologic deficits and infarction volumes. Further research
      revealed that 20 nm Au-NPs elevated the production of anti-inflammatory
      cytokines, as well as inhibited I/R induced activation of astrocytes and
      microglias. Moreover, the expressions of anti-apoptotic proteins were up
      regulated and the pro-apoptotic molecules were down-regulated in the post
      ischemic brains. These effects were opposite in 5 nm group. The above results
      showed that the neuroprotection of 20 nm Au-NPs was attributable to its anti
      inflammatory and anti-apoptotic effect. This study could provide a novel strategy
      for the treatment of cerebral I/R injury.

PMID- 23858967
TI  - Antitumor efficacy and tolerability of systemically administered gallium
      acetylacetonate-loaded gelucire-stabilized nanoparticles.
AB  - The widespread clinical success with most gallium compounds in cancer therapy is
      markedly hampered by lack of tumor specific accumulation, poor tumor permeability
      and undesirable toxicity to healthy tissues. The aim of this work was to
      investigate for the first time antitumor mechanism of a new gallium compound
      (gallium acetylacetonate; GaAcAc) while assessing effectiveness of gelucire
      stabilized nanoparticles (NPs) for potential application in gallium-based lung
      cancer therapy. NPs loaded with GaAcAc (Ga-NPs) were prepared using mixtures of
      cetyl alcohol with Gelucire 44/14 (Ga-NP-1) or Gelucire 53/13 (Ga-NP-2) as matrix
      materials. Of special note from this work is the direct evidence of involvement
      of microtubule disruption in antitumor effects of GaAcAc on human lung
      adenocarcinoma (A549). In-vivo tolerability studies were based on plasma ALT,
      creatinine levels and histopathological examination of tissues. The superior in
      vivo antitumor efficacy of Ga-NPs over GaAcAc was depicted in marked reduction of
      tumor weight and tumor volume as well as histological assessment of excised
      tumors. Compared to free GaAcAc, Ga-NPs showed a 3-fold increase in tumor-to
      blood gallium concentrations with minimized overall exposure to healthy tissues.
      Overall, enhancement of antitumor effects of GaAcAc by gelucire-stabilized NPs
      coupled with reduced exposure of healthy tissues to gallium would likely ensure
      desired therapeutic outcomes and safety of gallium-based cancer treatment.

PMID- 23858968
TI  - Micro-CT molecular imaging of tumor angiogenesis using a magnetite nano-cluster
      probe.
AB  - Due to its high resolution, micro-CT is desirable for molecular imaging of tumor
      angiogenesis. However, the sensitivity of micro-CT to contrast agents is
      relatively low. Therefore, the purpose of this study is to develop high micro-CT
      sensitive molecular imaging probes for direct visualization and dynamic
      monitoring of tumor angiogenesis. To this end, Arg-Gly-Asp (RGD) peptides
      conjugated magnetite nano clusters (RGD-MNCs) were developed by assembling
      individual magnetite nano particles into clusters with amphiphilic (maleimide)
      methoxypoly(ethylene glycol)-b-poly(lactic acid) ((Mal)mPEG-PLA) copolymer and
      subsequently encoding RGD peptides onto the clusters for specific targeting
      alpha(v)beta3 integrin. The hydrodynamic size of RGD-MNCs was about 85 nm. To
      test its specificity, alpha(v)beta3 positive cells (H1299) were incubated with
      magnetite nano clusters (MNCs), RGD-MNCs or RGD-MNCs competition with free RGD
      peptides. Prussian Blue staining and inductively coupled plasma optical emission
      spectrometer (ICP-OES) measurements indicated that the cell uptake of RGD-MNCs
      was significantly more than that of MNCs, which could be inhibited by free RGD
      peptides. For detection of tumor angiogenesis, mice bearing H1299 tumors were
      injected intravenously with RGD-MNCs at the dose of 400 micro mol Fe/kg. Tumor
      angiogenic hot spots as well as individual angiogenic vessels could be clearly
      manifested by micro-CT imaging 12 h post injection, which was dynamically
      monitored with the extension of probe circulation time. Subsequent histological
      studies of tumor tissues verified that RGD-MNCs registered tumor angiogenic
      vessels. Our study demonstrated that RGD-MNC probes fabricated in this study
      could be used to effectively target alpha(v)beta3 integrin. Using high resolution
      micro-CT in combination with the probes, tumor angiogenesis could be studied
      dynamically.

PMID- 23858969
TI  - Preliminary studies on palladium nanoparticle as a novel label for DNA microarray
      and their corresponding detection.
AB  - This paper firstly describes the preliminary results achieved by using palladium
      nanoparticle (Pd NP) as a novel label for the detection of DNA hybridization in
      DNA microarray. And two signal amplification procedures based on "the silver
      staining" or "the cobalt staining" are presented during above analysis. The
      results show that the label Pd NP-ssDNA (target) (single strand DNA(target))
      performs high single base pair mismatch-discrimination capability. The succeeding
      silver staining or cobalt staining procedure greatly amplifies such a signal
      through the catalysis of Pd. For "the silver staining:' the background staining
      is very low and the silver deposition only occurs around Pd NPs. So such a
      procedure provides a alternative for "Gold Label Silver Stain" presented by
      Mirkin C. A. For "the cobalt staining," not only a colorimetric array but also a
      magnetic sensor (such as Magnetic Tunnel Junction sensor, MTJ) can be used to
      detect the obtained cobalt dot due to its strong magnetic property, which
      provides a new strategy for DNA microarray detection. So as the proof-of-concept
      investigations, this work proved the feasibility of the application of Pd NPs as
      the label in DNA microarray assay.

PMID- 23858970
TI  - Enhancement of the sensitivity of surface plasmon resonance biosensor by
      modifying the metal surface.
AB  - We report on the enhancement of sensitivity of SPR biosensor by modifying the
      metal surface. A mixture layer, in which gold and dielectric medium coexist, was
      simply prepared by increasing the roughness of gold surface deposited onto a
      glass substrate via the reduction reaction. The absorbance spectrum and atomic
      force microscopy study showed that the average roughness of modified substrate
      increased by 4 times, compared to the unmodified substrate. The SPR curves of the
      unmodified substrate and the modified substrate were measured with the various
      refractive index of the dielectric medium. The sensitivity of modified substrate
      to the refractive index of dielectric medium was increased by 1.5 times, compared
      to the unmodified substrate. In result, the addition of the mixture layer between
      the gold surface and the dielectric medium by the reduction reaction can provides
      the enhancement of sensitivity in the SPR biosensor.

PMID- 23858971
TI  - Diffusion of single-walled carbon nanotube under physiological conditions.
AB  - Single-walled carbon nanotube (SWNT) can be functionalized to target cells for
      drug delivery or cancer cells for their detection and therapy. Understanding
      their transport phenomena in vivo is a necessary step to unlock their medical
      potential. This work estimates the diffusion characteristics of SWNTs and their
      DNA-conjugated bio-hybrids under simulated or postulated physiological conditions
      using EPI-fluorescence microscopy (EFM). SWNT was shortened and dispersed in
      aqueous solution with the average length and diameter of 253 nm (+/-30.6 nm) and
      1.6 nm (+/-0.34 nm), respectively, and tagged with a fluorophore, 1
      pyrenebutanoic succinimidyl ester (PSE), through non-covalent pi stacking. DNA
      was attached to the PSE-SWNTs through carboxiimide based coupling procedure.
      Using the EFM, real-time videos were recorded under four different viscosities
      corresponding to four kinds of human body fluids: lymph (1.4 cP), bile (2.4 cP),
      blood (3-6 cP), and cytoplasm (10-30 cP), and processed to calculate diffusion
      coefficients based on random walk and speed. At 37 degreeC, diffusion
      coefficients of the SWNTs were estimated to be: 1.45 (+/-0.652) x 10(4) nm2/s
      (lymph), 0.91 (+/-0.205) x 10(4) nm2/s (bile), 0.59 (+/-0.179)x 10(4) nm2/s
      (blood), and 0.26 (+/-0.114)x 10(4) nm2/s (cytoplasm). Estimated diffusion
      coefficients of SWNT-DNA bio-hybrids were: 1.45 (+/-0.402) x 10(4) nm2/s
      (plasma), 0.62 (+/-0.212) x 10(4) nm2/s (bile), 0.41 (+/-0.142) x 10(4) nm2/s
      (blood), 0.38 (+/-0.257) x 10(4) nm2/s (cytoplasm). These outcomes should serve
      as key data for developing mathematical models of SWNT-based drug delivery, cell
      targeting, and its biodistribution.

PMID- 23858972
TI  - In vitro analysis of the anti-cancer activity of mitoxantrone loaded on magnetic
      nanoparticles.
AB  - In this study, the anti-tumor activity of mitoxantrone loaded on magnetic
      nanoparticles (MTMP) was examined using DU145 prostate cancer cells. Composite
      nanoparticles with an average size of 20 nm were prepared using a chemical co
      precipitation technique. The MTMP nanoparticles were cytotoxic to DU145 cells and
      inhibited cell proliferation. The expression levels of apoptosis related proteins
      in DU145 cells, including PARP and caspase 3, were increased after MTMP
      treatment. In this study, the therapeutic potential of MTMP in targeted-therapy
      against prostate cancer was demonstrated and MTMP was more effective when coupled
      to drug delivery vehicle than pure mitoxantrone.

PMID- 23858973
TI  - Hydrolyzed galactomannan-modified nanoparticles and flower-like polymeric
      micelles for the active targeting of rifampicin to macrophages.
AB  - Inhalable nanocarriers that are uptaken by macrophages represent an appealing
      approach for the targeting of antibiotics to the tuberculosis reservoir. In the
      present work, we report on the development of rifampicin (RIF)-loaded
      nanoparticles and flower-like polymeric micelles surface-modified with hydrolyzed
      galatomannan (GalM-h), a polysaccharide of mannose and galactose, two sugars that
      are recognized by lectin-like receptors. Initially, pure or GalM-h-associated
      chitosan nanoparticles (NPs) were produced by ionotropic gelation. Despite the
      composition, NPs displayed positive zeta potential values between +18.0 and +24.5
      mV and a size ranging between 263 and 340 nm. In addition, RIF payloads were
      approximately 1.0% w/w. To increase the encapsulation efficiency, a more complex
      nanocarrier based on poly(epsilon-caprolactone)-b-poly(ethylene-glycol)-b
      poly(epsilon-caprolactone) flower-like polymeric micelles (PMs) coated with
      chitosan or GalM-h/chitosan were engineered. These polymeric micelles displayed a
      bimodal size distribution with a positive zeta potential between +6.7 and +8.1
      mV. More importantly, the drug encapsulation capacity was increased 12.9-fold
      with respect to the NPs. An agglutination assay with concanavalin A confirmed the
      presence of GalM-h on the surface. Qualitative uptake studies by fluorescence
      microscopy revealed that GalM-h-modified systems were taken-up by RAW 264.7
      murine macrophages. Finally, the intracellular/cell associated levels of RIF
      following the incubation of cells with free or encapsulated drug indicated that
      while chitosan hinders the uptake, GalM-h leads to a significant increase of the
      intracellular concentration.

PMID- 23858974
TI  - Analysis of beta amyloid peptides employing the small probe molecules.
AB  - We herein describe an analytical method employing a small molecule array for the
      characterization of similar proteins based on ligand binding. In this study, 2
      different beta amyloids (Abeta(1-40) and (1-42)) were selected as the model
      compounds. Their primary structures are identical except for 2 additional C
      terminal amino acids. However, many studies have observed different biological
      and chemical characteristics of these peptides. Thus, the ability to distinguish
      these 2 peptides is important in the diagnosis and development of treatments for
      related disorders such as Alzheimer's disease. However, strong non-specific
      binding is usually observed, even when specific antibodies for each peptide are
      employed. In this study, Abeta(1-40) and Abeta(1-42) peptides were immobilized on
      a typical 96-well microplate. Twenty different small probe molecules (modified
      amino acids conjugated with FITC) were applied to the peptides acting as the
      secondary antibodies and labeling compounds. The results show that specific
      binding patterns occurred according to Abeta type and the analysis of the
      patterns can be used to distinguish these 2 similar peptides.

PMID- 23858976
TI  - Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and
      safe insulin delivery system.
AB  - The aim of this work was to develop an efficient, biodegradable, biocompatible
      and safe controlled release system using insulin-loaded poly(epsilon
      caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were
      prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as
      emulsifier. Using the double emulsion method a high insulin encapsulation
      efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average
      particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles
      showed no toxicity to MIN6 cells. Insulin nanoparticles administered
      subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels
      after 15 minutes, and presented a sustainable hypoglycemic effect on insulin
      dependent type 1 diabetic rats, showing to be more efficient than unencapsulated
      insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by
      the effect over liver cell-death and oxidative stress scavenger system in rats.
      These results suggest that insulin-loaded PCL nanoparticles prepared by water-in
      oil-in-water emulsion method are biocompatible, efficient and safe insulin
      delivering system with controlled insulin release, which indicates that it may be
      a powerful tool for insulin-dependent patients care.

PMID- 23858975
TI  - Fibronectin and vitronectin promote human fetal osteoblast cell attachment and
      proliferation on nanoporous titanium surfaces.
AB  - Improvements in osteoconduction of implant biomaterials require focusing on the
      bone-implant interface, which is a complex multifactorial system. Surface
      topography of implants plays a crucial role at this interface. Nanostructured
      surfaces have been shown to promote serum protein adsorption and osteoblast
      adhesion when compared to micro-structured surfaces for bone-implant materials.
      We studied the influence of the serum proteins fibronectin and vitronectin on the
      attachment and proliferation of osteoblasts onto nanostructured titania surfaces.
      Human fetal osteoblastic cells hFOB 1.19 were used as model osteoblasts and were
      grown on nanoporous TiO2 templates, using Ti6AI4V and commercially pure Ti
      substrates as controls. Results show a significant increase in cell
      proliferation'on nanoporous TiO2 over flat substrates. Initial cell attachment
      data exhibited a significant effect by either fibronectin or vitronectin on cell
      adhesion at the surface of any of the tested materials. In addition, the extent
      of cell adhesion was significantly different between the nanoporous TiO2 and both
      Ti6AI4V and commercially pure Ti substrates, with the first showing the highest
      surface coverage. There was no significant difference on osteoblast attachment or
      proliferation between the presence of fibronectin or vitronectin using any of the
      material substrates. Taken together, these results suggest that the increase in
      osteoblast attachment and proliferation shown on the nanoporous TiO2 is due to an
      increase in the adsorption of fibronectin and vitronectin because of the higher
      surface area and to an enhanced protein unfolding, which allows access to
      osteoblast binding motifs within these proteins.

PMID- 23858977
TI  - Novel composed galactosylated nanodevices containing a ribavirin prodrug as
      hepatic cell-targeted carriers for HCV treatment.
AB  - In this paper, we describe the preparation of liver-targeted nanoparticles
      potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting
      the presence of carbohydrate receptors in the liver (i.e., ASGPR in hepatocytes).
      These particles were obtained starting from a galactosylated phospholipid
      polyaminoacid conjugate. This latter was obtained by chemical reaction of
      alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA
      EDA) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) sodium
      salt (DPPE), and subsequent reaction with lactose, obtaining PHEA-EDA-DPPE-GAL
      copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic
      RBV prodrug, i.e., RBV tripalmitate, was synthesized and its capability to
      release RBV in the presence of an adequate enzymatic activity was demonstrated.
      RBV tripalmitate-loaded nanoparticles were obtained starting from PHEA-EDA-DPPE
      GAL copolymer by using the dialysis method. These particles showed spherical
      shape and nanometric size. By in vitro experiments the absence of haemolytic
      activity of RBV tripalmitate-loaded PHEA-EDA-DPPE-GAL nanoparticles and their
      specificity toward HepG2 were demonstrated by using a competitive inhibition
      assay in the presence of free GAL and assessing nanoparticle uptake in the
      presence of free GAL and/or non-galactosylated nanoparticles. This finding raises
      hope in terms of future nanoparticle-based liver-targeted drug delivery strategy
      for the hepatitis C treatment.

PMID- 23858978
TI  - A comparison of extracellular excitatory amino acids release inhibition of acute
      lamotrigine and topiramate treatment in the hippocampus of PTZ-kindled epileptic
      rats.
AB  - In this communication, the effect of acute treatment with lamotrigine (LTG) and
      topiramate (TPM) was investigated on release of the main excitatory amino acids
      (EAA) such as glutamate (Glu) and aspartate (Asp) in the hippocampus of
      pentylenetetrazol (PTZ)-kindled freely moving rats using microdialysis. The
      results showed that the level of Glu and Asp significantly decreased in the PTZ
      kindled epileptic (EP) rat hippocampus after the 20 mg/kg LTG or 40 mg/kg TPM
      administration. But LTG gave rise to a better result than TPM in controlling EAA
      release.

PMID- 23858979
TI  - Guns and roses.

PMID- 23858980
TI  - Combined internal medicine-pediatrics program directors' professional activities.
AB  - OBJECTIVE: To list professional activities of dual boarded combined internal
      medicine-pediatrics (med-peds) program directors. METHODS: A national survey of
      all med-peds program directors conducted electronically in 2009. RESULTS: Of the
      74 dual boarded combined med-peds program directors, 72 (97 percent) completed
      the survey. The most common academic titles held in both departments were
      assistant professor (61 percent, n = 44) and associate professor (25 percent,
      n=18). Only one (1 percent) director did not have an academic title in either
      internal medicine or pediatrics departments. There were 16 program directors (22
      percent) that were additionally assistant or associate program director in
      categorical internal medicine residency programs and eight program directors (11
      percent) that were additionally either assistant or associate program director in
      categorical pediatric residency programs. Twelve program directors (17 percent)
      were also head of their med-peds section. There were 31 (43 percent) dual fellows
      of the American College of Physicians (ACP) and American Academy of Pediatrics
      (AAP). Twenty-five separate program directors (35 percent) participated in
      specific ACP and/or AAP activities. CONCLUSION: Med-Peds program directors hold
      dual academic titles, are involved in categorical internal medicine and
      pediatrics residency programs, and are involved in traditional pediatric and
      internal medicine professional societies. More detail about the academic
      promotion process and specific activity types of med-peds program directors
      should be further explored. WHAT'S NEW: This is the first article listing dual
      boarded med-peds program directors' academic titles and activities since combined
      residency programs became accredited by the Accreditation Council of Graduate
      Medical Education in 2006-2007.

PMID- 23858981
TI  - Medical Society of Delaware Policy Statement on Gun Control.

PMID- 23858982
TI  - Uncle Sam and your job options. Considering your next career move? Consider the
      tax implications.

PMID- 23858983
TI  - Healthcare in the United States.

PMID- 23858984
TI  - At the heart of integration: aligning physicians and administrators to create new
      value.
AB  - Because of its ability to create real incremental value for patients and
      providers, physician-hospital integration will continue to play a major role in
      transforming the way healthcare is delivered. Integration is more than a
      transaction, and without developing the right culture, new integrated
      organizations will struggle to transform their current model of care. Confronted
      with regulatory and specialty-specific environmental forces, cardiovascular
      physicians have integrated with health systems at a higher rate than other
      specialties have. In 2007, Piedmont Healthcare launched Piedmont Heart as the
      first integrated cardiovascular care delivery program affiliated with a community
      healthcare system in greater Atlanta. Piedmont Healthcare had successfully
      brought together hospitals and cardiovascular physicians in an organizational
      structure that allowed for the right culture, resulting in true integration and
      patient-centered care. Today, Piedmont Heart is one of the largest physician
      groups in the United States focused on delivering high-quality outcomes, aligning
      multidisciplinary cardiovascular initiatives, and allowing for smart, strategic
      growth. It has taken Piedmont Heart nearly five years to create new, incremental
      value from its center-of-excellence organizational structure, clinical pathways
      development, and Patient First program. Piedmont Heart had the advantage of
      starting earlier than many other physician-hospital integrated structures. As US
      healthcare moves from an industry driven by volume to one focused on value, it is
      organizations like Piedmont Heart that continue to drive smart integration
      forward and focus on innovation, despite potential disruption, that will be
      successful.

PMID- 23858985
TI  - Volume to value.
AB  - Traditional fee-for-service medicine has put physicians on an unsustainable
      treadmill of volume that escalates healthcare costs regardless of the quality of
      care they provide. This article shares the experience of UnityPoint Health
      (formerly Iowa Health System) in designing and implementing patient-centered,
      physician-led, coordinated care as a building block for transforming the delivery
      system. Keys to the effort's success include aligning physicians, hospitals, and
      home care delivery in terms of organizational goals and having the ability to
      gather, analyze, and share data to manage population health. On April 16, 2013,
      Iowa Health System became UnityPoint Health, dedicated to transforming the
      delivery of care through a coordinated system that offers regional, organized
      systems of care in most of our markets in Iowa and Illinois. These capabilities
      allowed the system to enter into value-based accountable care organization
      contracts that cover more than 220,000 lives. The transition ultimately will lead
      to population health-driven approaches in which compensation will be based on the
      management of specific populations or chronic diseases over a specified period.
      As increased value from care coordination becomes clear, the external environment
      will demand this better system, and patients will expect it.

PMID- 23858986
TI  - Physician-led models of accountability and value: observations on payment policy
      and culture.

PMID- 23858987
TI  - Collaboration across clinical silos.
AB  - We face significant challenges to healthcare integration as well as tremendous
      opportunities to advance healthcare reform as we endeavor to provide a
      coordinated continuum of high-value services to defined populations for which we
      are clinically and fiscally accountable. As we move away from fee-for-service and
      poorly coordinated care toward value-based and bundled care, systems such as
      UnityPoint Health and clinical entities such as Piedmont Heart are leading the
      way, breaking down their clinical silos, improving value and access, and gaining
      patient loyalty. Evidence points us to sound principles that can inform the
      clinical integration process. Health systems must reinvent themselves, reengineer
      clinical operations, and streamline processes, all of which require collaboration
      across traditional silos, both inside our organizations and outside into our
      wider communities, to ensure that our patients receive the safe, high-value care
      they deserve.

PMID- 23858988
TI  - Breaking down clinical silos in healthcare.

PMID- 23858989
TI  - Stratospheric ozone, global warming, and the principle of unintended consequences
      -an ongoing science and policy success story.

PMID- 23858990
TI  - Stratospheric ozone, global warming, and the principle of unintended consequences
      -an ongoing science and policy success story.
AB  - In 1974, Mario Molina and F. Sherwood Rowland warned that chlorofluorocarbons
      (CFCs) could destroy the stratospheric ozone layer that protects Earth from
      harmful ultraviolet radiation. In the decade after scientists documented the
      buildup and long lifetime of CFCs in the atmosphere; found the proof that CFCs
      chemically decomposed in the stratosphere and catalyzed the depletion of ozone;
      quantified the adverse effects; and motivated the public and policymakers to take
      action. In 1987, 24 nations plus the European Community signed the Montreal
      Protocol. Today, 25 years after the Montreal Protocol was agreed, every United
      Nations state is a party (universal ratification of 196 governments); all parties
      are in compliance with the stringent controls; 98% of almost 100 ozone-depleting
      chemicals have been phased out worldwide; and the stratospheric ozone layer is on
      its way to recovery by 2065. A growing coalition of nations supports using the
      Montreal Protocol to phase down hydrofluorocarbons, which are ozone safe but
      potent greenhouse gases. Without rigorous science and international consensus,
      emissions of CFCs and related ozone-depleting substances (ODSs) could have
      destroyed up to two-thirds of the ozone layer by 2065, increasing the risk of
      causing millions of cancer cases and the potential loss of half of global
      agricultural production. Furthermore, because most, ODSs are also greenhouse
      gases, CFCs and related ODSs could have had the effect of the equivalent of 24-76
      gigatons per year of carbon dioxide. This critical review describes the history
      of the science of stratospheric ozone depletion, summarizes the evolution of
      control measures and compliance under the Montreal Protocol and national
      legislation, presents a review of six separate transformations over the last 100
      years in refrigeration and air conditioning (A/C) technology, and illustrates
      government-industry cooperation in continually improving the environmental
      performance of motor vehicle A/C.

PMID- 23858991
TI  - Fuel-based fine particulate and black carbon emission factors from a railyard
      area in Atlanta.
AB  - Railyards have the potential to influence localfine particulate matter
      (aerodynamic diameter < or = 2.5 microm; PM2.5) concentrations through emissions
      from diesel locomotives and supporting activities. This is of concern in urban
      regions where railyards are in proximity to residential areas. Northwest of
      Atlanta, Georgia, Inman and Tilford railyards are located beside residential
      neighborhoods, industries, and schools. The PM2.5 concentrations near the
      railyards is the highest measured amongst the state-run monitoring sites (Georgia
      Environmental Protection Division, 2012;
      http://www.georgiaair.org/amp/report.php). The authors estimated fuel-based black
      carbon (BC) and PM2.5 emission factors for these railyards in order to help
      determine the impact of railyard activities on PM2.5 concentrations, and for
      assessing the potential benefits of replacing current locomotive engines with
      cleaner technologies. High-time-resolution measurements of BC, PM2.5, CO2, and
      wind speed and direction were made at two locations, north and south of the
      railyards. Emissions factors (i.e., the mass of BC or PM2.5 per gallon of fuel
      burned) were estimated by using the downwind/upwind difference in concentrations,
      wavelet analysis, and an event-based approach. By the authors' estimates, diesel
      electric engines used in the railyards have average emission factors of 2.8 +/-
      0.2 g of BC and 6.0 +/- 0.5 g of PM2.5 per gallon of diesel fuel burned. A
      broader mix of railyard supporting activities appear to lead to average emission
      factors of 0.7 +/- 0.03 g of BC and 1.5 +/- 0.1 g of PM2.5 per gallon of diesel
      fuel burned. Railyard emissions appear to lead to average enhancements of
      approximately 1.7 +/- 0.1 microg/m3 of PM2.5 and approximately 0.8 +/- 0.01
      microg/m3 of BC in neighboring areas on an annual average basis. Uncertainty not
      quantified in these results could arise mainly from variability in
      downwind/upwind differences, differences in emissions of the diverse zones within
      the railyards, and the influence of on-road mobile source emissions.

PMID- 23858992
TI  - Chemical characteristics of fine particulate matters measured during severe
      winter haze events in Ulaanbaatar, Mongolia.
AB  - In order to investigate the chemical characteristics of atmospheric aerosol
      measured during a severe winter haze event, 12-hr PM2.5 (particulate matter with
      an aerodynamic diameter < or = 2.5 microm) samples were collected at an urban
      site in Ulaanbaatar Mongolia, from January 9 to February 17, 2008. On average, 12
      hr PM2.5 mass concentration was 105.1 +/- 34.9 microg/m3. Low PM2.5 mass
      concentrations were measured when low pressure developed over central Mongolia.
      The 12-hr average organic mass by carbon (OMC) varied from 6.4 to 132.3
      microg/m3, with a mean of 54.9 +/- 25.4 microg/m3, whereas elemental carbon (EC)
      concentration ranged from 0.1 to 3.6 microgC/m3, with a mean of 1.5 +/- 0.8
      microgC/m3. Ammonium sulfate was found to be the most abundant water-soluble
      ionic component in Ulaanbaatar during the sampling period, with an average
      concentration of 11.3 +/- 5.0 microg/m3. In order to characterize the effect of
      air mass pathway on fine particulate matter characteristics, 5-day back
      trajectory analysis was conducted, using the Hybrid Single-Particle Lagrangian
      Integrated Trajectory (HYSPLIT) model. The haze level was classified into three
      categories, based on the 5-day air mass back trajectories, as Stagnant (ST),
      Continental (CT), and Low Pressure (LP) cases. PM2.5 mass concentration during
      the Stagnant condition was approximately 2.5 times higher than that during the
      Low Pressure condition, mainly due to increased pollutant concentration of OMC
      and secondary ammonium sulfate.

PMID- 23858993
TI  - An evaluation of the toxicological aspects and potential doses from the
      inhalation of coal combustion products.
AB  - This paper reviews toxicological literature pertaining to coal combustion
      products (CCPs) inhalation and presents case studies on the inhalation of CCPs
      from the Kingston Fossil Plant area and from the Colbert Fossil Plant CCP
      landfill site. While most research regarding coal plant emissions focuses on fly
      ash, this article takes a holistic approach to examining not only emitted
      particulate matter such as fly ash, but also the theoretical calculated doses of
      landfilled CCPs. Furthermore, these doses are compared to in vitro and in vivo
      studies in order to highlight differences between laboratory-based studies and to
      emphasize the difficulty in extrapolating effects from inhalation exposures. In
      both case studies, fugitive emissions from the Kingston ash spill or the Colbert
      CCP-handling operations did not exceed any national ambient air quality standards
      or reference concentrations for individual components. Adverse effects such as
      mild pulmonary inflammation noted in the reviewed literature were in response to
      doses much higher than would be likely to occur in humans exposed to landfilled
      CCPs. We conclude that the doses for fugitive emissions calculated herein do not
      appear to be high enough to elicit a measurable adverse response in humans.

PMID- 23858994
TI  - Testing and modeling the influence of reclamation and control methods for
      reducing nonpoint mercury emissions associated with industrial open pit gold
      mines.
AB  - Industrial gold mining is a significant source of mercury (Hg) emission to the
      atmosphere. To investigate ways to reduce these emissions, reclamation and dust
      and mercury control methods used at open pit gold mining operations in Nevada
      were studied in a laboratory setting. Using this information along with field
      data, and building off previous work, total annual Hg emissions were estimated
      for two active gold mines in northern Nevada. Results showed that capping mining
      waste materials with a low-Hg substrate can reduce Hg emissions from 50 to nearly
      100%. The spraying of typical dust control solutions often results in higher Hg
      emissions, especially as materials dry after application. The concentrated
      application of a dithiocarbamate Hg control reagent appears to reduce Hg
      emissions, but further testing mimicking the actual distribution of this chemical
      within an active leach solution is needed to make a more definitive assessment.

PMID- 23858995
TI  - Effect of anionic-nonionic-mixed surfactant micelles on solubilization of PAHs.
AB  - The solubility enhancement of phenanthrene (Phe), fluoranthene (FLT), and
      benzo[a]pyrene (BaP) in water by the single anionic surfactant sodium dodecyl
      sulfate (SDS), single nonionic surfactant Triton X-100 (TX100), and mixed
      surfactant solution (SDS-TX100) with varying proportions and the synergism
      mechanism were investigated in detail. Solubilization of phenanthrene was greatly
      enhanced either by SDS or by TX100. The sequence of solubilization for different
      mixed-surfactant solutions or surfactant solutions was SDS-TX100 (1:9, liquid
      mass ratio) > TX100 > SDS-TX100 (2:8) > SDS-TX100 (3:7) > SDS-TX100 (4:6) > SDS
      TX100 (1:1) > SDS-TX100 (7:3) > SDS when the concentrations were above their
      critical micelle concentration (CMC). The composite surfactant SDS-TX100 (1.9)
      had better solubilization capacity than any single surfactant, which is
      attributed to the lower CMC of the mixed surfactant solution and the increase of
      the molar solubilization ratio (MSR) of the solution. The linear relationship
      between the solubility values of three targets polycyclic aromatic hydrocarbons
      (PAHs) and the polarities of the microenvironments of pyrene with SDS-TX100
      mixtures has been demonstrated, with a linear regression coefficient of 0.7331,
      0.7658, and 0.8669, respectively. The optimum mixed micelles of the anionic and
      nonionic surfactants (SDS-TX100; 1:9) had lower polarity and higher aggregation
      number This indicated that more PAHs were transferred into the mixed micelles of
      the anionic and nonionic surfactants.

PMID- 23858996
TI  - Using pollution roses to assess sulfur dioxide impacts in a township downwind of
      a petrochemical complex.
AB  - This study used pollution roses to assess sulfur dioxide (SO) pollution in a
      township downwind of a large petrochemical complex based on data collected from a
      single air quality monitoring station. The pollution roses summarized hourly SO2
      concentrations at the Taishi air quality monitoring station, located
      approximately 7.8-13.0 km south of the No. 6 Naphtha Cracking Complex in Taiwan,
      according to 36 sectors of wind direction during the preoperational period (1995
      1999) and two postoperational periods (2000-2004 and 2005-2009). The 99th
      percentile of hourly SO2 concentrations 350 degrees downwind from the complex
      increased from 28.9 ppb in the preoperational period to 86.2-324.2 ppb in the two
      postoperational periods. Downwind SO2 concentrations were particularly high
      during 2005-2009 at wind speeds of 6-8 m/sec. Hourly SO2 levels exceeded the US.
      Environmental Protection Agency (EPA) health-based standard of 75 ppb only in the
      postoperational periods, with 65 exceedances from 0-10 degrees and 330-350
      degrees downwind directions during 2001-2009. This study concluded that pollution
      roses based on a single monitoring station can be used to investigate source
      contributions to air pollution surrounding industrial complexes, and that it is
      useful to combine such directional methods with analyses of how pollution varies
      between different wind speeds, times of day, and periods of industrial
      development.

PMID- 23858997
TI  - Compromising economic cost and air pollutant emissions of municipal solid waste
      management strategies by fuzzy multiobjective optimization model.
AB  - Municipal solid waste management (MSWM) is an important environmental challenge
      and subject in urban planning. A sustainable MSWM strategy should consider not
      only economic efficiency but also life-cycle assessment of environmental impact.
      This study employs the fuzzy multiobjective linear programming (FMOLP) technique
      to find the optimal compromise between economic optimization and pollutant
      emission reduction for the MSWM strategy. Taichung City in Taiwan is evaluated as
      a case study. The results indicate that the optimal compromise MSWM strategy can
      reduce significant amounts of pollutant emissions and still achieve positive net
      profits. Minimization of the sulfur oxide (SOx) and nitrogen oxide (NOx)
      emissions are the two major priorities in achieving this optimal compromise
      strategy when recyclables recovery rate is lower; however minimization of the
      carbon monoxide (CO) and particulate matter (PM) emissions become priority
      factors when recovery rate is higher.

PMID- 23858998
TI  - Accounting for acceleration and deceleration emissions in intersection dispersion
      modeling using MOVES and CAL3QHC.
AB  - Near-road dispersion modeling with CAL3QHC has traditionally been accomplished by
      assuming vehicles are either idling in queue links or flowing freely in cruise
      links. With the introduction of the new mobile-source emissions model MOVES,
      second-by-second activity patterns can be used to produce emission factors (EFs)
      that vary by vehicular modal activity, that is, acceleration, deceleration, idle,
      and cruise. By using these EFs in unique modal links in CAL3QHC input files, the
      predicted concentration of pollutants near roadways can be modeled with greater
      precision in regard to real-world intersection vehicle behavior. It is noted that
      this work does not include any comparisons with real-world monitored data, and
      thus only the precision and not the accuracy of the proposed method is addressed.
      This work poses the question of how best to include modal links into near-road
      dispersion modeling. Specifically, it examines dividing acceleration and
      deceleration segments into multiple sublinks for greater resolution. It is shown
      that such an approach can produce much higher CO predictions at an intersection
      (up to 400% higher) compared with the current cruise-and-idle-links modeling
      approach. A method of dividing links by increments of speed change is suggested.
      The method relies upon obtaining EFs from standstill to various cruise speeds (or
      from cruise speed to stopped) and using those results to obtain position-specific
      acceleration (or deceleration) EFs needed for dispersion modeling inputs.
      Acceleration EFs (in g/mile) are an order of magnitude larger than cruise EFs;
      deceleration EFs are smaller than cruise EFs. The number of sublinks used to
      model one acceleration link makes a difference in the predicted concentrations.
      MOVES can produce erratic EFs when longer links are broken into smaller sublinks.

PMID- 23858999
TI  - Decreasing trends of suspended particulate matter and PM2.5 concentrations in
      Tokyo, 1990-2010.
AB  - In Tokyo, the annual average suspended particulate matter (SPM) and PM2.5
      concentrations have decreased in the past two decades. The present study
      quantitatively evaluated these decreasing trends using data from air-pollution
      monitoring stations. Annual SPM and PM2.5 levels at 83 monitoring stations and
      hourly SPM and PM2.5 levels at four monitoring stations in Tokyo, operated by the
      Tokyo Metropolitan Government, were used for analysis, together with levels of co
      pollutants and meteorological conditions. Traffic volume in Tokyo was calculated
      from the total traveling distance of vehicles as reported by the Ministry of
      Land, Infrastructure, Transport, and Tourism. High positive correlations between
      SPM levels and nitrogen oxide levels, sulfur dioxide levels, and traffic volume
      were determined. The annual average SPM concentration declined by 62.6%from 59.4
      microg/m3 in 1994 to 22.2 microg/m3 in 2010, and PM2.5 concentration also
      declined by 49.8% from 29.3 microg/m3 in 2001 to 14.7 microg/m3 in 2010.
      Likewise, the frequencies of hourly average SPM and PM2.5 concentrations
      exceeding the daily guideline values have significantly decreased since 2001 and
      the hourly average SPM or PM2.5 concentrations per traffic volume for each time
      period have also significantly decreased since 2001. However SPM and PM2.5
      concentrations increased at some monitoring stations between 2004 and 2006 and
      from 2009 despite strengthened environmental regulations and improvements in
      vehicle engine performance. The annual average SPM and PM2.5 concentrations were
      positively correlated with traffic volumes and in particular with the volume of
      diesel trucks. These results suggest that the decreasing levels of SPM and PM2.5
      in Tokyo may be attributable to decreased traffic volumes, along with the effects
      of stricter governmental regulation and improvements to vehicle engine
      performance, including the fitting of devices for exhaust emission reduction.

PMID- 23859000
TI  - Synthesis and biological activities of 2,6-dihydroxy-4-isopentenyloxychalcone as
      an antimicrobial and anti-inflammatory compound.
AB  - Chalcones are a group of plant-derived polyphenolic compounds possessing a wide
      variety of biological activities. The aim of this study was to synthesize 2,6
      dihydroxy-4-isopentenyloxychalcone (1), a chalcone found in plants belonging to
      the genera Helichrysum, Pleiotaxix and Metalasia, and evaluate its antimicrobial
      effects against major oral pathogens as well as its anti-inflammatory properties.
      Compound 1 was synthesized using a simple two-step procedure. Among the seven
      pathogens tested, Porphyromonas gingivalis and Prevotella intermedia were the
      most susceptible to inhibition by 1. This chalcone also attenuated the secretion
      of interleukin-8 and chemokine (C-C motif) ligand 5 (CCL5) by lipopolysaccharide
      (LPS)-stimulated oral epithelial cells as well as the secretion of matrix
      metalloproteinase 2 (MMP-2) by LPS-stimulated gingival fibroblasts. In
      conclusion, our study showed that 1 exerts a dual effect by acting on both oral
      pathogens and the host inflammatory response and thus represents a molecule of
      interest for periodontal infections. 

PMID- 23859001
TI  - Fluoroquinolone levels in healthy dog urine following a 20-mg/kg oral dose of
      enrofloxacin exceed mutant prevention concentration targets against Escherichia
      coli isolated from canine urinary tract infections.
AB  - A 3-day course of oral enrofloxacin is effective for treating uncomplicated
      urinary tract infection (UTI) in dogs when administered 20 mg/kg Q24H. However,
      emergence of fluoroquinolone-resistant mutants of uropathogens is a concern.
      Urine concentrations of enrofloxacin and ciprofloxacin were measured in six
      healthy dogs following dose of enrofloxacin 20 mg/kg. Mutant prevention
      concentrations of Escherichia coli isolated from canine UTI were also determined
      against ciprofloxacin. Urine AUC(24)/MPC ratios considering ciprofloxacin
      concentrations ranged 3819-7767, indicating that selection of resistant E. coli
      mutants in dogs with uncomplicated UTIs is unlikely in the bladder given that an
      AUC(24)/MPC = 39 is considered to be protective against mutant selection for
      ciprofloxacin. However, additional studies are required to evaluate the effects
      of this enrofloxacin treatment protocol on bacteria that colonize anatomic sites
      where fluoroquinolones achieve lower concentrations compared to the urinary
      bladder. 

PMID- 23859002
TI  - Optimality of a time-dependent treatment profile during an epidemic.
AB  - The emergence and spread of drug resistance is one of the most challenging public
      health issues in the treatment of some infectious diseases. The objective of this
      work is to investigate whether the effect of resistance can be contained through
      a time-dependent treatment strategy during the epidemic subject to an
      isoperimetric constraint. We apply control theory to a population dynamical model
      of influenza infection with drug-sensitive and drug-resistant strains, and solve
      the associated control problem to find the optimal treatment profile that
      minimizes the cumulative number of infections (i.e. the epidemic final size). We
      consider the problem under the assumption of limited drug stockpile and show that
      as the size of stockpile increases, a longer delay in start of treatment is
      required to minimize the total number of infections. Our findings show that the
      amount of drugs used to minimize the total number of infections depends on the
      rate of de novo resistance regardless of the initial size of drug stockpile. We
      demonstrate that both the rate of resistance emergence and the relative
      transmissibility of the resistant strain play important roles in determining the
      optimal timing and level of treatment profile. 

PMID- 23859003
TI  - Finding simple rules for discriminating folding rate change upon single mutation
      by statistical and learning methods.
AB  - Protein folding rate is a valuable clue for understanding the variations in
      protein folding kinetics. The ability to accurately discriminate protein folding
      rate change is very helpful in protein design. However, there are fewer studies
      on the influence of amino acid substitution to protein folding rates. In our
      earlier studies, we constructed a dataset of 467 mutants upon amino acid
      substitution and proposed novel methods for discriminating and predicting the
      accelerating and decelerating mutants during the folding process. This study
      aimed to effectively develop simple rules for discriminating accelerating mutants
      from decelerating ones upon single amino acid substitution. The main points of
      the study were to build a more general dataset F661 with 661 mutants, analyze the
      dataset systematically, and then implement different data mining techniques to
      build discrimination rules. Furthermore, the rules obtained from different
      methods were interpreted, evaluated, compared and integrated. The results
      appeared that the present approach may effectively develop simple rules from
      these mutants and the quality of the rules may be improved by combining the
      statistical and learning methods. These results suggest that the present method,
      as well as the rules, may advance the understanding of discriminating protein
      folding rate change. The details of the rules along with relevant information
      have been integrated and available freely at
      http://bioinformatics.myweb.hinet.net/rulefr.htm. 

PMID- 23859004
TI  - Field-induced single-ion magnets based on enantiopure chiral beta-diketonate
      ligands.
AB  - A pair of homochiral beta-diketonate ligands (+)-3-trifluoroacetyl)camphor (d
      Htfc) and (-)-3-trifluoroacetyl)camphor (l-Htfc) were used to construct two
      enantiomeric pairs of Dy(III) single-ion magnets [Dy(d-tfc)3(bpy)]2 (d-1)/[Dy(l
      tfc)3(bpy)]2 (l-1) (bpy = 2,2'-bipyridine) and [Dy(d-tfc)3(phen)].2H2O (d
      2)/[Dy(l-tfc)3(phen)] (l-2) (phen = 1,10-phenanthroline). The capping aromatic
      N,N'-donors have a dramatic influence on the structural and magnetic
      characteristics of the Dy(III) beta-diketonate enantiomeric pairs: the cocrystal
      of two homochiral Dy(III) beta-diketonate stereoisomers with the 2,2'-bipyridine
      ligand was formed, showing field-induced single-ion magnet behaviors with a two
      step relaxation process, while no stereoisomerization happened for the homochiral
      Dy(III) beta-diketonate with the 1,10-phenanthroline coligand, exhibiting a
      single relaxation process of the magnetization only. The anisotropy barriers of d
      1 (36.5 and 46.1 K) are slightly smaller than those of l-1 (37.0 and 49.3 K),
      while d-2 has a larger energy barrier (30.5 K) with respect to l-2 (25.1 K). 

PMID- 23859005
TI  - Personality disorders and health problems distinguish suicide attempters from
      completers in a direct comparison.
AB  - BACKGROUND: Whether suicide attempters and completers represent the same
      population evaluated at different points along a progression towards suicide
      death, overlapping populations, or completely different populations is a problem
      still unresolved. METHODS: 446 Adult suicide attempters and knowledgeable
      collateral informants for 190 adult suicide probands were interviewed.
      Sociodemographic and clinical data was collected for both groups using semi
      structured interviews and structured assessments. Univariate analyses and
      logistic regression models were conducted to explore the similarities and
      differences between suicide attempters and completers. RESULTS: Univariate
      analyses yielded significant differences in sociodemographics, recent life
      events, impulsivity, suicide intent, and distribution of Axis I and II disorders.
      A logistic regression model aimed at distinguishing suicide completers from
      attempters properly classified 90% of subjects. The most significant variables
      that distinguished suicide from attempted suicide were the presence of
      narcissistic personality disorder (OR=21.4; 95% CI=6.8-67.7), health problems
      (OR=20.6; 95% CI=5.6-75.9), male sex (OR=9.6; 95% CI=4.42-20.9), and alcohol
      abuse (OR=5.5; 95% CI=2.3-14.2). LIMITATIONS: Our study shares the limitations of
      studies comparing suicide attempters and completers, namely that information from
      attempters can be obtained from the subject himself, whereas the assessment of
      completers depends on information from close family or friends. Furthermore,
      different semi-structured instruments assessed Axis I and Axis II disorders in
      suicide attempters and completers. Finally, we have no data on inter-rater
      reliability data. CONCLUSIONS: Suicide completers are more likely to be male and
      suffer from alcohol abuse, health problems (e.g. somatic illness), and
      narcissistic personality disorder. The findings emphasize the importance of
      implementing suicide prevention programs tailored to suicide attempters and
      completers.

PMID- 23859006
TI  - Nanostructure formation and transition from surface to bulk degradation in
      polyethylene glycol gels chain-extended with short hydroxy acid segments.
AB  - Degradable, in situ gelling, inert hydrogels with tunable properties are very
      attractive as a matrix for cell encapsulation and delivery to the site of
      regeneration. Cell delivery is generally limited by the toxicity of gelation and
      degradation reactions. The objective of this work was to investigate by
      simulation and experimental measurement gelation kinetics and degradation rate of
      star acrylated polyethylene glycol (PEG) macromonomers chain-extended with short
      hydroxy acid (HA) segments (SPEXA) as a function of HA monomer type and number of
      HA repeat units. HA monomers included least hydrophobic glycolide (G), lactide
      (L), p-dioxanone (D), and most hydrophobic epsilon-caprolactone (C). Chain
      extension of PEG with short HA segments resulted in micelle formation for all HA
      types. There was a significant decrease in gelation time of SPEXA precursor
      solutions with HA chain-extension for all HA types due to micelle formation,
      consistent with the simulated increase in acrylate-acrylate (Ac-Ac) and Ac
      initiator integration numbers. The hydrolysis rate of SPEXA hydrogels was
      strongly dependent on HA type and number of HA repeat units. SPEXA gels chain
      extended with the least hydrophobic glycolide completely degraded within days,
      lactide within weeks, and p-dioxanone and epsilon-caprolactone degraded within
      months. The wide range of degradation rates observed for SPEXA gels can be
      explained by large differences in equilibrium water content of the micelles for
      different HA monomer types. A biphasic relationship between HA segment length and
      gel degradation rate was observed for all HA monomers, which was related to the
      transition from surface (controlled by HA segment length) to bulk (controlled by
      micelle equilibrium water content) hydrolysis within the micelle phase. To our
      knowledge, this is the first report on transition from surface to bulk
      degradation at the nanoscale in hydrogels.

PMID- 23859007
TI  - Stereoselective synthesis of hexahydro-1H-pyrano- and thiopyrano[3,4-c]quinoline
      derivatives through a Prins cascade cyclization.
AB  - A cascade reaction of (E)-5-(arylamino)pent-3-en-1-ols and thiols with various
      aldehydes in the presence of 30 mol % BF3.OEt2 in 1,2-dichloroethane at 80 
      degrees C affords a novel class of trans-fused hexahydro-1H-pyrano[3,4
      c]quinolines and hexahydro-1H-thiopyrano[3,4-c]quinolines in good to excellent
      yields with high selectivity. The condensation of (Z)-5-(arylamino)pent-3-en-1-ol
      with aldehydes provides the corresponding cis-fused products under similar
      conditions. 

PMID- 23859008
TI  - Fixed energy X-ray absorption voltammetry.
AB  - In this paper, the fixed energy X-ray absorption voltammetry (FEXRAV) is
      introduced. FEXRAV represents a novel in situ X-ray absorption technique for fast
      and easy preliminary characterization of electrode materials and consists of
      recording the absorption coefficient at a fixed energy while varying at will the
      electrode potential. The energy is chosen close to an X-ray absorption edge, in
      order to give the maximum contrast between different oxidation states of an
      element. It follows that any shift from the original oxidation state determines a
      variation of the absorption coefficient. Although the information given by FEXRAV
      obviously does not supply the detailed information of X-ray absorption near edge
      structure (XANES) or extended X-ray absorption fine structure (EXAFS), it allows
      to quickly map the oxidation states of the element under consideration within the
      selected potential windows. This leads to the rapid screening of several systems
      under different experimental conditions (e.g., nature of the electrolyte,
      potential window) and is preliminary to more deep X-ray absorption spectroscopy
      (XAS) characterizations, like XANES or EXAFS. In addition, the time-length of the
      experiment is much shorter than a series of XAS spectra and opens the door to
      kinetic analysis. 

PMID- 23859009
TI  - Origin of anomalous water permeation through graphene oxide membrane.
AB  - Water inside the low-dimensional carbon structures has been considered seriously
      owing to fundamental interest in its flow and structures as well as its practical
      impact. Recently, the anomalous perfect penetration of water through graphene
      oxide membrane was demonstrated although the membrane was impenetrable for other
      liquids and even gases. The unusual auxetic behavior of graphene oxide in the
      presence of water was also reported. Here, on the basis of first-principles
      calculations, we establish atomistic models for hybrid systems composed of water
      and graphene oxides revealing the anomalous water behavior inside the stacked
      graphene oxides. We show that formation of hexagonal ice bilayer in between the
      flakes as well as melting transition of ice at the edges of flakes are crucial to
      realize the perfect water permeation across the whole stacked structures. The
      distance between adjacent layers that can be controlled either by oxygen
      reduction process or pressure is shown to determine the water flow thus
      highlighting a unique water dynamics in randomly connected two-dimensional
      spaces. 

PMID- 23859010
TI  - Short-term effects of an oral contraceptive containing oestradiol valerate and
      dienogest on bone metabolism and bone mineral density: an observational,
      preliminary study.
AB  - OBJECTIVES: To evaluate the effects of a combined oral contraceptive (COC)
      containing dienogest/oestradiol valerate (DNG/E2V) on bone mineral density (BMD)
      and on serum and urinary bone turnover markers in young, healthy, fertile women.
      METHODS: At baseline and after three and six months of intake of the
      aforementioned COC, serum and urinary calcium, osteocalcin, urinary pyridinoline
      (PYD), and deoxypyridinoline (D-PYD) of 30 women aged 21 to 34 years were
      measured. At baseline and after six months, lumbar bone mineral density was
      determined by dual-energy X-ray absorptiometry (DEXA). RESULTS: Urinary levels of
      PYD and D-PYD were significantly lower at three and six months in comparison with
      basal values (p < 0.05). Serum calcium levels showed an increasing trend, which
      reached statistical significance after six months in comparison with basal values
      while urinary levels of calcium did not vary significantly. Serum osteocalcin
      levels were somewhat, but not significantly, lower during pill use in comparison
      with basal values. After six months, spinal BMD values did not differ
      significantly from basal values. CONCLUSIONS: The DNG/E2V COC has no short-term
      adverse effect on bone turnover markers. No significant change in BMD was
      observed after six months of use of that pill.

PMID- 23859011
TI  - Optimal fungicide application timings for disease control are also an effective
      anti-resistance strategy: a case study for Zymoseptoria tritici (Mycosphaerella
      graminicola) on wheat.
AB  - Strategies to slow fungicide resistance evolution often advocate early
      "prophylactic" fungicide application and avoidance of "curative" treatments where
      possible. There is little evidence to support such guidance. Fungicide
      applications are usually timed to maximize the efficiency of disease control
      during the yield-forming period. This article reports mathematical modeling to
      explore whether earlier timings might be more beneficial for fungicide resistance
      management compared with the timings that are optimal for efficacy. There are two
      key timings for fungicide treatment of winter wheat in the United Kingdom: full
      emergence of leaf three (counting down the canopy) and full emergence of the flag
      leaf (leaf 1). These timings (referred to as T1 and T2, respectively) maximize
      disease control on the upper leaves of the crop canopy that are crucial to yield.
      A differential equation model was developed to track the dynamics of leaf
      emergence and senescence, epidemic growth, fungicide efficacy, and selection for
      a resistant strain. The model represented Zymoseptoria tritici on wheat treated
      twice at varying spray timings. At all fungicide doses tested, moving one or both
      of the two sprays earlier than the normal T1 and T2 timings reduced selection but
      also reduced efficacy. Despite these opposing effects, at a fungicide dose just
      sufficient to obtain effective control, the T1 and T2 timings optimized fungicide
      effective life (the number of years that effective control can be maintained). At
      a higher dose, earlier spray timings maximized effective life but caused some
      reduction in efficacy, whereas the T1 and T2 timings maximized efficacy but
      resulted in an effective life 1 year shorter than the maximum achievable.

PMID- 23859012
TI  - The physiological and pathophysiological roles of adipocyte miRNAs.
AB  - MicroRNAs (miRNAs) are highly conserved, small, noncoding RNAs that regulate gene
      expression at the posttranscriptional level. Their actions affect numerous
      important biological processes, including adipocyte differentiation and function,
      sugar and lipid metabolism, and insulin production and secretion. Recent reports
      suggest miRNAs may also be involved in the pathogenic processes of obesity,
      diabetes, and insulin resistance. In this review, we summarize research
      progresses on adipocyte miRNAs and their physiological and pathological
      implications. 

PMID- 23859013
TI  - Optimizing dimodular nonribosomal peptide synthetases and natural dipeptides in
      an Escherichia coli heterologous host.
AB  - Nonribosomal peptides are an important class of natural products that have a
      broad range of biological activities. Their structural complexity often prevents
      simple chemical synthesis, and production from the natural producer is often low,
      which deters pharmaceutical development. Expression of biosynthetic machinery in
      heterologous host organisms like Escherichia coli is one way to access these
      structures, and subsequent optimization of these systems is critical for future
      development. We utilized the aureusimine biosynthetic gene cluster as a model
      system to identify the optimal conditions to produce nonribosomal peptides in the
      isopropyl beta-d-1-thiogalactopyranoside (IPTG)-inducible T7 promoter system of
      pET28. Single reaction monitoring of nonribosomal products was used to find the
      optimal concentration of IPTG, postinduction temperature, and the effect of amino
      acid precursor supplementation. In addition, principle component analysis of
      these extracts identified 3 previously undiscovered pyrazine products of the
      aureusimine biosynthetic locus, highlighting the utility of heterologously
      expressing nonribosomal peptide synthetases to find new products. 

PMID- 23859014
TI  - Research on DNA methylation of human osteosarcoma cell MGMT and its relationship
      with cell resistance to alkylating agents.
AB  - The objective of this study was to explore the O(6)-methylguanine-DNA
      methyltransferase (MGMT) gene methylation status and its protein expression, as
      well as the effects of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on
      MGMT gene expression and its resistance to alkylating agents, and to elucidate
      MGMT expression mechanism and significance in osteosarcoma. The human
      osteosarcoma cell lines Saos-2 and MG-63 were collected and treated with 5-Aza
      CdR for 6 days. The cells not treated with 5-Aza-CdR were set as a negative
      control. The genomic DNA was extracted from the Saos-2 and MG-63 cells using
      methylation-specific PCR to detect the promoter CpG island methylation status of
      the MGMT gene. Cell sensitivity to alkylating agents before and after drug
      administration was detected by the MTT method. The variation in MGMT gene mRNA
      and protein was detected by reverse transcription PCR (RT-PCR) and Western
      blotting. The MGMT promoter gene of normal Saos-2 cells was methylated, with
      reduced MGMT mRNA and protein expression; the MGMT mRNA and protein expression of
      Saos-2 cells treated with 5-Aza-CdR was obviously enhanced, and its sensitivity
      to alkylating agents was reversed. Meanwhile, with promoter CpG island
      unmethylation of the MGMT gene, MGMT protein was expressed in the normal MG-63
      cells and the MG-63 cells treated with 5-Aza-CdR, and both showed resistance to
      alkylating agents. The methylation status of the MGMT gene promoter in human
      osteosarcoma cells reflected the cells' ability to induce MGMT protein expression
      and can be used as a molecular marker to project the sensitivity of cancer
      tissues to alkylating agent drugs. 

PMID- 23859015
TI  - Low expression of dendritic cell-specific intercellular adhesion molecule
      grabbing nonintegrin-related protein in non-Hodgkin lymphoma and significant
      correlations with lactic acid dehydrogenase and beta2-microglobulin.
AB  - Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin
      related protein (DC-SIGNR), a type II integral membrane protein and a member of
      the C-type lectins, has been reported to bind various strains of HIV-1, HIV-2,
      and simian immunodeficiency virus. Serum DC-SIGNR is not currently available for
      the detection of non-Hodgkin lymphoma (NHL). Using an enzyme-linked immunosorbent
      assay (ELISA), we assessed the serum levels of DC-SIGNR in 70 cancer patients and
      100 healthy controls. Additionally, using immunohistochemistry, we determined the
      expression of DC-SIGNR in the lymph nodes. Using the ELISA, low serum levels of
      DC-SIGNR were detected in the patients (median, 4.513 ng.L(-1); range, 1.066
      9.232 ng.L(-1); p = 0.0003). Serum concentrations of DC-SIGNR correlated
      significantly with age (p = 0.0077) and lactic acid dehydrogenase (p = 0.0046)
      and beta2-microglobulin (p = 0.0491) levels. However, we found no statistically
      significant correlation between serum DC-SIGNR levels and clinical data such as
      sex, Ann Arbor stage, B symptoms, and histologic subtypes. Moreover, NHL patients
      with a lower level of serum DC-SIGNR expression in lymphatic endothelial cells
      also showed negative immunostaining levels. These results suggest that DC-SIGNR
      is a biological molecule that may be potentially useful in NHL clinical settings.

PMID- 23859016
TI  - Enhanced 5-fluorouracil cytotoxicity in high COX-2 expressing hepatocellular
      carcinoma cells by wogonin via the PI3K/Akt pathway.
AB  - Combination therapies may increase the antitumor effects and reduce the adverse
      effects for the treatment of hepatocellular carcinoma. In this study, we
      determined the effects of 5-fluorouracil alone or in combination with wogonin in
      vitro and in vivo, and we investigated the possible mechanisms. The combination
      of these 2 drugs led to a decrease in survival and a significant synergistic
      inhibitory effect on high COX-2 expression in SMMC-7721 hepatocellular carcinoma
      (HCC) cells. Furthermore, the results show that this combination inhibits COX-2
      expression and increases sensitivity to chemotherapeutic agents partly through
      regulating the PI3K/Akt signaling pathway. Moreover, the combination treatment
      caused a significant growth inhibition of human tumor xenografts in vivo. In
      conclusion, wogonin may increase the cytotoxicity of some antineoplastic agents
      and it can be used in combination with these agents as a novel therapeutic
      regimen for HCC treatment. 

PMID- 23859017
TI  - The effect of sodium nitroprusside on survival and stress signaling in PC12 rat
      phaeochromocytoma cells expressing a dominant negative RasH mutant protein.
AB  - Toxic concentrations of the second messenger nitric oxide cause cellular stress
      leading to cell death. Ras proteins, possible targets of nitric oxide-induced
      nitrosylation, may act as mediators in nitrosative stress. To analyze the
      possible involvement of Ras proteins in nitric oxide cytotoxicity, a PC12 rat
      phaeochromocytoma cell line expressing a dominant negative Ras mutant protein was
      used in this study. Cytotoxic concentrations of the nitric oxide donor sodium
      nitroprusside activated several proapoptotic mechanisms, including stimulation of
      the stress kinase pathways mediated by c-Jun N-terminal kinase (JNK) and p38
      mitogen-activated protein kinase (MAPK), inhibition of the translation initiation
      factor eIF2alpha, induction and phosphorylation of the p53 protein, and inhibited
      Akt-mediated antiapoptotic signaling, independent of Ras function.
      Simultaneously, Ras-dependent stimulation of the prosurvival ERK pathway was also
      observed, followed by an increased activation of the caspase-9/caspase-3 cascade
      in cells with impaired Ras function. It is concluded that nitric oxide
      stimulation of multiple signaling pathways contributes to the cell death program,
      whereas concomitant activation of the Ras/ERK pathway provides a certain degree
      of protection. 

PMID- 23859018
TI  - Retinol binding protein 4 affects the adipogenesis of porcine preadipocytes
      through insulin signaling pathways.
AB  - Retinol binding protein 4 (RBP4), a novel cytokine, is mainly secreted by
      hepatocytes and adipocytes. RBP4 reportedly induces insulin resistance and RBP4
      secretion is increased in the adipocytes of animals or humans with type 2
      diabetes, obesity, and metabolic syndrome, but its role in preadipocyte
      differentiation remains unclear. In this study, we investigated the effect of
      RBP4 on the differentiation of porcine preadipocytes into adipocytes. The results
      suggest that RBP4 significantly suppresses the differentiation of porcine
      preadipocytes into adipocytes, including those treated with the hormone cocktail
      methylisobutylxanthine-dexamethasone-insulin. RBP4 also weakened the activity of
      normal threonine 308, the phosphorylation of serine/threonine kinase AKT, and
      downstream insulin signaling, including the mammalian target of rapamycin (mTOR)
      and beta-catenin. Moreover, the activation of insulin signaling mediated by
      knockdown RBP4 in porcine preadipocytes was recovered in the suppression of
      LY294002. RBP4 also had a suppressive effect on the differentiation of porcine
      preadipocytes by decreasing the activation of insulin signaling pathways. 

PMID- 23859019
TI  - A novel protein from Eupolyphaga sinensis inhibits adhesion, migration, and
      invasion of human lung cancer A549 cells.
AB  - Eupolyphaga sinensis Walker is an important insect used in Chinese traditional
      medicine. In this study, we purified a 72-kDa anticancer protein, designated as
      EPS72, from this species using ammonium sulfate precipitation, ultrafiltration,
      CM Sepharose Fast Flow cation exchange, Q Sepharose High Performance (HP) anion
      exchange, Butyl Sepharose HP hydrophobic chromatography, and Superdex 75 gel
      filtration chromatographic techniques. EPS72 exhibited a potent anticancer
      activity against the human lung cancer A549 cell line (IC50, 18.76 MUg/mL).
      Further study showed that EPS72 could induce A549 cell detachment and apoptosis,
      inhibit cell adhesion to fibronectin and collagen IV, and restrain cell migration
      and invasion. Moreover, EPS72 significantly decreased the expression of beta1
      integrin. This study suggests that EPS72 could potentially be developed as a
      novel anticancer therapeutic agent due to its possible antimetastatic activity. 

PMID- 23859020
TI  - Supraphysiological expression of survival motor neuron protein from an adenovirus
      vector does not adversely affect cell function.
AB  - Spinal muscular atrophy (SMA) is the most common inherited neurodegenerative
      disease that leads to infant mortality. It is caused by mutations in the survival
      motor neuron (SMN) protein resulting in death of alpha motor neurons. Increasing
      evidence suggests that several other tissues are also affected in SMA, including
      skeletal and cardiac muscle, liver, and pancreas, indicating that systemic
      delivery of therapeutics may be necessary for true disease correction. Due to the
      natural biodistribution of therapeutics, a level of SMN several-fold above
      physiological levels can be achieved in some tissues. In this study, we address
      whether supraphysiological levels of SMN adversely affects cell function.
      Infection of a variety of cell types with an adenovirus (Ad) vector encoding SMN
      leads to very high expression, but the resulting protein correctly localizes
      within the cell, and associates with normal cellular partners. Although SMN
      affects transcription of certain target genes and can alter the splicing pattern
      of others, we did not observe any difference in select target gene splicing or
      expression in cells overexpressing SMN. However, normal human fibroblasts treated
      with Ad-SMN showed a slight reduction in growth rate, suggesting that certain
      cell types may be differently impacted by high levels of SMN. 

PMID- 23859021
TI  - The influence of phosphorylation of prothymosin alpha on its nuclear import and
      antiapoptotic activity.
AB  - Phosphorylation of prothymosin alpha (ProTalpha) appears not to affect its
      influence on chromatin remodelling. To determine whether it affects nuclear
      import or cytosolic antiapoptotic activity, cells were transfected with vectors
      generating tagged recombinant ProTalpha (rProTalpha), either wild-type
      (rProTalpha-wt), which is partially phosphorylated posttranslation or the
      nonphosphorylatable rProTalpha-T7A. Immunofluorescence microscopy showed the
      predominant location of native ProTalpha, rProTalpha-wt, and rProTalpha-T7A in
      the nucleus. The activity of caspases 9 and 3 following apoptosis induction
      treatment (staurosporine) indicated reduction of apoptosis by rProTalpha-wt but
      not by rProTalpha-T7A. It is concluded that phosphorylation of ProTalpha is
      required for its antiapoptotic activity, but it does not affect its nuclear
      import. 

PMID- 23859022
TI  - Did the prion protein become vulnerable to misfolding after an evolutionary
      divide and conquer event?
AB  - Despite high sequence identity among mammalian prion proteins (PrPs), mammals
      have varying rates of susceptibility to prion disease resulting in a so-called
      species barrier. The species barrier follows no clear pattern, with closely
      related species or similar sequences being no more likely to infect each other,
      and remains an unresolved enigma. Variation of the conformationally flexible
      regions may alter the thermodynamics of the conformational change, commonly
      referred to as the conformational conversion, which occurs in the pathogenic
      process of the mammalian prion protein. A conformational ensemble scenario is
      supported by the species barrier in prion disease and evidence that there are
      strains of pathogenic prion with different conformations within species. To study
      how conformational flexibility has evolved in the prion protein, an investigation
      was undertaken on the evolutionary dynamics of structurally disordered regions in
      the mammalian prion protein, non-mammalian prion protein that is not vulnerable
      to prion disease, and remote homologs Doppel and Shadoo. Structural disorder
      prediction analyzed in an evolutionary context revealed that the occurrence of
      increased or altered conformational flexibility in mammalian PrPs coincides with
      key events among PrP, Doppel, and Shadoo. Comparatively rapid evolutionary
      dynamics of conformational flexibility in the prion protein suggest that the
      species barrier is not a static phenomenon. A small number of amino acid
      substitutions can repopulate the conformational ensemble and have a
      disproportionately large effect on pathogenesis. 

PMID- 23859023
TI  - How important is vehicle safety for older consumers in the vehicle purchase
      process?
AB  - OBJECTIVE: This study aimed to investigate the importance of vehicle safety to
      older consumers in the vehicle purchase process. METHODS: Older (n = 102), middle
      aged (n = 791), and younger (n = 109) participants throughout the eastern
      Australian states of Victoria, New South Wales, and Queensland who had recently
      purchased a new or used vehicle completed an online questionnaire about their
      vehicle purchase process. RESULTS: When asked to list the 3 most important
      considerations in the vehicle purchase process (in an open-ended format), older
      consumers were mostly likely to list price as their most important consideration
      (43%). Similarly, when presented with a list of vehicle factors (such as price,
      design, Australasian New Car Assessment Program [ANCAP] rating), older consumers
      were most likely to identify price as the most important vehicle factor (36%).
      When presented with a list of vehicle features (such as automatic transmission,
      braking, air bags), older consumers in the current study were most likely to
      identify an antilock braking system (41%) as the most important vehicle feature,
      and 50 percent of older consumers identified a safety-related vehicle feature as
      the highest priority vehicle feature (50%). When asked to list up to 3 factors
      that make a vehicle safe, older consumers in the current study were most likely
      to list braking systems (35%), air bags (22%), and the driver's behavior or skill
      (11%). When asked about the influence of safety in the new vehicle purchase
      process, one third of older consumers reported that all new vehicles are safe
      (33%) and almost half of the older consumers rated their vehicle as safer than
      average (49%). A logistic regression model was developed to predict the profile
      of older consumers more likely to assign a higher priority to safety features in
      the vehicle purchasing process. The model predicted that the importance of safety
      related features was influenced by several variables, including older consumers'
      beliefs that they could protect themselves and their family from a crash, their
      traffic infringement history, and whether they had children. CONCLUSIONS: These
      findings are consistent with previous research that suggests that, though older
      consumers highlight the importance of safety features (i.e., seat belts, air
      bags, braking), they often downplay the role of safety in their vehicle
      purchasing process and are more likely to equate vehicle safety with the presence
      of specific vehicle safety features or technologies rather than the vehicle's
      crash safety/test results or crashworthiness. The findings from this study
      provide a foundation to support further research in this area that can be used by
      policy makers, manufacturers, and other stakeholders to better target the
      promotion and publicity of vehicle safety features to particular consumer groups
      (such as older consumers). Better targeted campaigns may help to emphasize the
      value of safety features and their role in reducing the risk of injury/death. If
      older consumers are better informed of the benefits of safety features when
      purchasing a vehicle, a further reduction in injuries and deaths related to motor
      vehicle crashes may be realized.

PMID- 23859024
TI  - Women's intentions to breastfeed: a population-based cohort study.
AB  - OBJECTIVE: Given that intention to breastfeed is a strong predictor of
      breastfeeding initiation and duration, the objectives of this study were to
      estimate the population-based prevalence and the factors associated with the
      intention to breastfeed. DESIGN: Retrospective population-based cohort study.
      SETTING: All hospitals in Ontario, Canada (1 April 2009-31 March 2010).
      POPULATION: Women who gave birth to live, term, singletons/twins. METHODS:
      Patient, healthcare provider, and hospital factors that may be associated with
      intention to breastfeed were analysed using univariable and multivariable
      regression. MAIN OUTCOME MEASURES: Population-based prevalence of intention to
      breastfeed and its associated factors. RESULTS: The study included 92,364 women,
      of whom 78,806 (85.3%) intended to breastfeed. The odds of intending to
      breastfeed were higher amongst older women with no health problems and women who
      were cared for exclusively by midwives (adjusted OR 3.64, 95% CI 3.13-4.23).
      Being pregnant with twins (adjusted OR 0.73, 95% CI 0.57-0.94), not attending
      antenatal classes (adjusted OR 0.58, 95% CI 0.54-0.62), having previous term or
      preterm births (adjusted OR 0.79, 95% CI 0.78-0.81, and adjusted OR 0.87, 95% CI
      0.82-0.93, respectively), and delivering in a level-1 hospital (adjusted OR 0.85,
      95% CI 0.77-0.93) were associated with a lower intention to breastfeed.
      CONCLUSIONS: In this population-based study ~85% of women intended to breastfeed
      their babies. Key factors that are associated with the intention to breastfeed
      were identified, which can now be targeted for intervention programmes aimed at
      increasing the prevalence of breastfeeding and improving overall child and
      maternal health.

PMID- 23859025
TI  - An investigation of thin-film Ni-Fe oxide catalysts for the electrochemical
      evolution of oxygen.
AB  - A detailed investigation has been carried out of the structure and
      electrochemical activity of electrodeposited Ni-Fe films for the oxygen evolution
      reaction (OER) in alkaline electrolytes. Ni-Fe films with a bulk and surface
      composition of 40% Fe exhibit OER activities that are roughly 2 orders of
      magnitude higher than that of a freshly deposited Ni film and about 3 orders of
      magnitude higher than that of an Fe film. The freshly deposited Ni film increases
      in activity by as much as 20-fold during exposure to the electrolyte (KOH);
      however, all films containing Fe are stable as deposited. The oxidation of
      Ni(OH)2 to NiOOH in Ni films occurs at potentials below the onset of the OER.
      Incorporation of Fe into the film increases the potential at which Ni(OH)2/NiOOH
      redox occurs and decreases the average oxidation state of Ni in NiOOH. The Tafel
      slope (40 mV dec(-1)) and reaction order in OH(-) (1) for the mixed Ni-Fe films
      (containing up to 95% Fe) are the same as those for aged Ni films. In situ Raman
      spectra acquired in 0.1 M KOH at OER potentials show two bands characteristic of
      NiOOH. The relative intensities of these bands vary with Fe content, indicating a
      change in the local environment of Ni-O. Similar changes in the relative
      intensities of the bands and an increase in OER activity are observed when pure
      Ni films are aged. These observations suggest that the OER is catalyzed by Ni in
      Ni-Fe films and that the presence of Fe alters the redox properties of Ni,
      causing a positive shift in the potential at which Ni(OH)2/NiOOH redox occurs, a
      decrease in the average oxidation state of the Ni sites, and a concurrent
      increase in the activity of Ni cations for the OER. 

PMID- 23859026
TI  - Ignoring the forest and the trees: vaccine antigen study is overmatched.

PMID- 23859027
TI  - Reply: To PMID 23545349.

PMID- 23859028
TI  - Treatment of experimental esophagogastric myotomy with bone marrow mesenchymal
      stem cells in a rat model.
AB  - BACKGROUND: Over the last 15 years, many studies demonstrated the myogenic
      regenerative potential of bone marrow mesenchymal stem cells (BM-MSC), making
      them an attractive tool for the regeneration of damaged tissues. In this study,
      we have developed an animal model of esophagogastric myotomy (MY) aimed at
      determining the role of autologous MSC in the regeneration of the lower
      esophageal sphincter (LES) after surgery. METHODS: Syngeneic BM-MSC were locally
      injected at the site of MY. Histological and functional analysis were performed
      to evaluate muscle regeneration, contractive capacity, and the presence of green
      fluorescent protein-positive BM-MSC (BM-MSC-GFP(+) ) in the damaged area at
      different time points from implantation. KEY RESULTS: Treatment with syngeneic BM
      MSC improved muscle regeneration and increased contractile function of damaged
      LES. Transplanted BM-MSC-GFP(+) remained on site up to 30 days post injection.
      Immunohistochemical analysis demonstrated that MSC maintain their phenotype and
      no differentiation toward smooth or striated muscle was shown at any time point.
      CONCLUSIONS & INFERENCES: Our data support the use of autologous BM-MSC to both
      improve sphincter regeneration of LES and to control the gastro-esophageal reflux
      after MY.

PMID- 23859029
TI  - Soy food consumption and lung cancer risk: a meta-analysis using a common measure
      across studies.
AB  - A published meta-analysis pooled individual studies by using the study-specific
      odds ratio (OR) or relative risk (RR) for the highest vs. lowest category of soy
      or isoflavone intake from each study, but it should be problematic to make
      comparison between studies/populations for lung cancer risk as the quantiles are
      so different from different studies/populations. Therefore, we conducted a meta
      analysis to explore the association between exposure of estimated daily soy
      protein intake in grams and lung cancer risk. We extracted ORs or RRs and 95%
      confidence intervals (CIs), converted them to the estimated ones for daily soy
      protein intake and pooled them using fixed or random effects models from 11
      epidemiologic studies. Overall, the inverse association between daily grams of
      soy protein intake and risk of lung cancer was borderline statistically
      significant (OR = 0.98, 95% CI = 0.96 to 1.00); the inverse association was
      statistically significant in nonsmokers (OR = 0.96; 95% CI = 0.93 to 0.99) and
      stronger than in smokers (P for difference <0.05). No statistical significance
      for the associations was observed between genders, the origin of the
      participants, study design and types of soy intake. This study suggests a
      borderline reduction in risk of lung cancer with daily soy protein intake in
      grams, and a significant inverse association in nonsmokers. 

PMID- 23859030
TI  - Adherence to World Cancer Research Fund/American Institute for Cancer Research
      lifestyle recommendations reduces prostate cancer aggressiveness among African
      and Caucasian Americans.
AB  - The effect of adherence to the World Cancer Research Fund (WCRF) lifestyle
      recommendations on cancer aggressiveness is unknown. We examined associations
      between adherence to recommendations and risk of highly aggressive prostate
      cancer in research subjects enrolled in the North Carolina-Louisiana Prostate
      Cancer Project (PCaP). We examined associations between adherence to WCRF
      recommendations and risk of highly aggressive prostate cancer among 2212 newly
      diagnosed African Americans (AA) or Caucasian Americans (CA) aged 40-70 years in
      PCaP. Prostate cancer aggressiveness was based on Gleason scores, serum prostate
      specific antigens, and TNM stage. Adherence to WCRF recommendations was based on
      point scores and odds ratios estimated. Results showed that adherence to
      recommendations was significantly and negatively associated with risk of a highly
      aggressive prostate cancer. Each additional point in the total adherence score
      corresponded to a 13% risk reduction. Total adherence score <4 predicted
      increased risk in both AA (OR = 1.36; 95% CI = 1.01-1.85) and CA (OR = 1.41; 95%
      CI = 1.01-1.98). Consumption of <500 g red meat per week or <=125 total kcal/100
      g solid food per day is a statistically significant protective factor in the
      overall cohort. Recommendations aimed at preventing all cancers also may reduce
      risk of highly aggressive prostate cancer.

PMID- 23859031
TI  - The effect of grapefruit intake on endogenous serum estrogen levels in
      postmenopausal women.
AB  - Although grapefruit intake leads to elevated serum estrogen levels when hormones
      are taken orally, there are no published data on the effect on endogenous levels.
      We conducted a pilot dietary intervention study among healthy postmenopausal
      volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine
      participants were recruited through the Love/Avon Army of Women. The study
      consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight
      fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4,
      8, and 10 hr after grapefruit intake were collected during an acute-phase study
      for 10 women. Serum assays for estrone (E1), estradiol (E2), estrone-3-sulfate
      (E1S), dehydroepiandrosterone sulfate, and sex hormone-binding globulin were
      conducted. Whole grapefruit intake had significant effects on endogenous E1S.
      Peak effects were seen at 8 hr, increasing by 26% from baseline. No changes in
      mean E1 or E2 with whole fruit intake were observed. In contrast, fresh juice,
      bottled juice, and soda intake all had significant lowering effects on E2. The
      findings suggest an important interaction between grapefruit intake and
      endogenous estrogen levels. Because endogenous estrogen levels are associated
      with breast cancer risk, further research is warranted. 

PMID- 23859032
TI  - Differences in vitamin D nutritional status between newly diagnosed cancer
      patients from rural or urban settings in Kentucky.
AB  - Although poor nutritional status and weight loss in cancer patients is known to
      affect outcomes, little is known about malnutrition differences based on
      geographic location. We investigated nutritional and inflammatory status of 220
      newly diagnosed adults with solid tumors at the University of Kentucky's Markey
      Cancer Center during December 2008 through October 2011. Chi-square tests were
      used to determine any associations between suboptimal nutritional levels and
      rural-urban areas of residence. Out of the 13 lab values collected, the only
      significant difference between rural and urban participants was found for vitamin
      D resulting in more rural subjects (67.4%) having a suboptimal vitamin D status
      as compared to those residing in urban areas (53.3%, P = 0.04). Controlling for
      baseline demographics including age, race, sex, body mass index, nutritional
      status, and type of cancer, logistic regression analyses concluded those in rural
      areas had nearly a twofold increase in the odds of having a suboptimal vitamin D
      level compared to those in urban areas (odd's ratio = 1.97; 95% confidence
      interval = 1.04, 3.74). Further investigation into the rural-urban differences in
      vitamin D needs to be investigated in order to improve outcomes during cancer
      treatment. 

PMID- 23859033
TI  - Dietary intake of B vitamins and methionine and colorectal cancer risk.
AB  - B vitamins are involved in 1-carbon metabolism, which is necessary for DNA
      replication, DNA repair, and regulation of gene expression. Recent studies
      suggest inverse associations between folate and vitamin B6 intakes and colorectal
      cancer risk but associations with other B vitamins and methionine have not been
      widely studied. After following 14,645 men and 22,467 women for 15 yr on average,
      we ascertained 910 incident colorectal cancers. Dietary intakes were estimated
      using a 121-item food frequency questionnaire. Hazard ratios (HRs) and 95%
      confidence intervals were estimated using Cox regression. We found some evidence
      of a U-shaped relationship between colon cancer risk and vitamin B6 and an
      inverse U-shaped relationship between rectal cancer risk and B12 (test for the
      quadratic trend, P = 0.005 and P = 0.0005 respectively). For colon cancer, we
      observed a reduced risk associated with low methionine/high folate, HR = 0.63
      (0.49, 0.80) and an increased risk associated with high methionine/high folate,
      HR = 1.36 (1.06, 1.74) (P interaction < 0.0001). Our study suggests a U-shaped
      association between colon cancer risk and vitamin B6 intake and an inverse U
      shaped association between rectal cancer risk and vitamin B12. Adequate folate
      intake might protect against colon cancer risk in those with low methionine
      intake.

PMID- 23859034
TI  - Cruciferous vegetables consumption and risk of renal cell carcinoma: a meta
      analysis.
AB  - Previous cohort and case-control studies on the association between cruciferous
      vegetables consumption and risk of renal cell carcinoma have illustrated
      conflicting results so far. To demonstrate the potential association between
      them, a meta-analysis was performed. Eligible studies were retrieved via both
      computerized searches and review of references. The summary relative risks (RRs)
      with 95% confidence interval (CI) for the highest vs. the lowest consumption of
      cruciferous vegetables were calculated. Heterogeneity and publication bias were
      also evaluated. Stratified analyses were performed as well. Three cohort and 7
      case-control studies were included. A significantly decreased risk with renal
      cell carcinoma was observed in overall cruciferous vegetables consumption group
      (RR = 0.73; 95% CI, 0.63-0.83) and subgroup of case-control studies (RR = 0.69;
      95% CI, 0.60-0.78), but not in cohort studies (RR = 0.96; 95% CI, 0.71-1.21). No
      heterogeneity and publication bias were detected across studies. Our findings
      supported that cruciferous vegetables consumption was related to the decreased
      risk of renal cell carcinoma. Because of the limited number of studies, further
      well-designed prospective studies and researches need to be conducted to better
      clarify the protective effect of cruciferous vegetables on renal cell carcinoma
      and potential mechanism. 

PMID- 23859035
TI  - Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.
AB  - Epidemiologic evidence supports that diets rich in polyphenols promote health and
      may delay the onset of colon cancer. Cocoa and chocolate products have some of
      the highest polyphenolic concentrations compared to other polyphenolic food
      sources. This study tested the hypothesis that a diet including dark chocolate
      can protect against colon cancer by inhibiting aberrant crypt foci (ACF)
      formation, downregulating gene expression of inflammatory mediators, and
      favorably altering cell kinetics. We also investigated whether bloomed dark
      chocolate retains the antioxidant capacity and protects against colon cancer.
      Forty-eight rats received either a diet containing control (no chocolate),
      regular dark chocolate, or bloomed dark chocolate and were injected
      subcutaneously with saline or azoxymethane. Relative to control, both regular and
      bloomed dark chocolate diets lowered the total number of ACF (P = 0.022).
      Chocolate diet-fed animals downregulated transcription levels of COX-2 (P =
      0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index
      (P = 0.001). These results suggest that a diet including dark chocolate can
      reduce cell proliferation and some gene expression involving inflammation, which
      may explain the lower number of early preneoplastic lesions. These results
      provide new insight on polyphenol-rich chocolate foods and colon cancer
      prevention. 

PMID- 23859036
TI  - Antioxidants delay clinical signs and systemic effects of ENU induced brain
      tumors in rats.
AB  - According to our previous study suggesting that antioxidant properties of
      phytochemicals in the diet decrease glioma aggressiveness, we used a SUVIMAX-like
      diet ("Supplementation en VItamines et Mineraux AntioXydants") (enriched with
      alpha-tocopherol, beta carotene, vitamin C, zinc, and sodium selenite), adapted
      to rats. The present results showed that each of the antioxidants inhibited
      growth of glioma cells in vitro. When used in combination for in vivo studies, we
      showed a highly significant delay in the clinical signs of the disease, but not a
      statistical significant difference in the incidence of glioma in an Ethyl
      nitrosourea (ENU)-model. The SUVIMAX-like diet decreased candidate markers of
      tumoral aggressiveness and gliomagenesis progression. The mRNA expressions of 2
      common markers in human glioma: Mn-SOD (Manganese Superoxide Dismutase) and
      IGFBP5 (insulin growth factor binding protein) were reduced in the tumors of rats
      fed the antioxidant diet. In addition, the transcripts of two markers linked to
      brain tumor proliferation, PDGFRb (platelet-derived growth factor receptor beta)
      and Ki-67, were also significantly decreased. On the whole, our results suggest a
      protective role for antioxidants to limit aggressiveness and to some extent,
      progression of gliomas, in a rat model. 

PMID- 23859037
TI  - Maternal dietary canola oil suppresses growth of mammary carcinogenesis in female
      rat offspring.
AB  - As suggested by rodent studies and studies using human breast cancer cells,
      dietary canola oil is linked with lower breast cancer risk. Here, we investigated
      the effect of maternal (pregnancy plus lactation) dietary canola oil on the
      susceptibility of female Sprague-Dawley rat offspring to mammary carcinogenesis.
      Although the control diet had 10% soybean oil, the treatment diet was formulated
      to contain 10% canola oil as a fat source. N-nitroso-N-methylurea was injected to
      induce mammary cancer in offspring. The offspring of canola-fed dams showed
      significantly decreased tumor multiplicity (1.0 +/- 0.3 vs. 1.9 +/- 0.3,
      respectively; P = 0.04) and tumor volume (1232.5 +/- 771.0 mm(3) vs. 6,302.5 +/-
      1,747.4 mm(3), respectively; P = 0.01), along with increased survival rate (87%
      vs. 47%, respectively; P = 0.01). In addition, the mRNA expression of development
      related gamma-glutamyltransferase 1 was significantly higher in the lactating
      mammary tissues of the canola group dams and mammary tumor tissues of the
      offspring [2.5 +/- 0.6 vs. 0.5 +/- 0.2, respectively (P = 0.01) and 0.98 +/- 0.03
      vs. 0.56 +/- 0.15, respectively (P = 0.05)]. These results suggest a potential
      anticancer effect of maternal dietary canola oil and may be useful in devising
      prenatal nutritional strategies to reduce breast cancer risk in humans.

PMID- 23859038
TI  - Low-glucose conditions of tumor microenvironment enhance cytotoxicity of
      tetrathiomolybdate to neuroblastoma cells.
AB  - Growth of tumor cells depends on sufficient supply of fermentable substrate, such
      as glucose. This provokes development of new anticancer therapies based on
      dietary restrictions. However, some tumor cells can lower their glucose
      dependency and activate processes of ATP formation/saving to retain viability
      even in limited glucose supply. In addition, tumor cells often lose sensitivity
      to many conventional anticancer drugs in the low-glucose conditions. Thus,
      development of the drugs effectively killing the tumor cells in nutrient-limited
      conditions is necessary. In this study, we show an enhanced cytotoxicity of
      tetrathiomolybdate, the drug exhibiting antiangiogenic and tumor-suppressing
      effects, to neuroblastoma SH-SY5Y and SK-N-BE(2) cells in the low-glucose
      conditions. This preference results from the tetrathiomolybdate-induced
      upregulation of cell dependency on glucose. The cells treated with
      tetrathiomolybdate increase the uptake of glucose, production of lactate,
      activate the Akt- and AMPK-signaling pathways and downregulate COX IV. In cells
      growing in the low-glucose conditions, these events result in significant
      decrease of the intracellular ATP supply and apoptosis. We propose
      tetrathiomolybdate as suitable agent to be used in combination with dietary
      restrictions in therapy of neuroblastoma. 

PMID- 23859039
TI  - Diallyl trisulfide is more cytotoxic to prostate cancer cells PC-3 than to
      noncancerous epithelial cell line PNT1A: a possible role of p66Shc signaling
      axis.
AB  - Diallyl trisulfide (DATS) is an organosulfur compound isolated from garlic, and
      has been shown to have anticancer activity both in vitro and in vivo. The aim of
      this study was to compare cytotoxic effects of DATS on prostate cancer cells PC-3
      and noncancerous human prostate epithelial cells PNT1A. PC-3 prostate cancer and
      noncancerous human prostate epithelial cells PNT1A were used in the study. We
      observed that PNT1A cells had higher resistance to DATS-induced cell death than
      PC-3 cells. Investigating signaling pathways involved in the cell death we
      observed that p66Shc phosphorylation at serine 36 and extracellular signal
      regulated kinase 1/2 activation induced by DATS, were significantly attenuated in
      PNT1A cells as compared to PC-3 cells. Moreover, DATS-induced Akt inactivation
      was also significantly reduced in PNT1A cells. In addition to that, DATS-induced
      reactive oxygen species generation was nearly completely abolished in PNT1A
      cells. Interestingly, DATS induced only slight decrease in the level of ferritin
      H, whereas ferritin L was elevated. These data suggest that cytotoxicity of DATS
      toward PNT1A cells is strongly reduced as opposed to PC-3 cancer cells, which
      corresponds to the lower activation of prodeath signaling pathway mediated by the
      adaptor protein p66Shc in the noncancerous PNT1A cells. 

PMID- 23859040
TI  - Epicatechin gallate induces cell death via p53 activation and stimulation of p38
      and JNK in human colon cancer SW480 cells.
AB  - The tea flavonoid epicatechin gallate (ECG) exhibits a wide range of biological
      activities. In this study, the in vitro anticancer effects of ECG on SW480 colon
      cancer cell line was investigated by analyzing the cell cycle, apoptosis, key
      proteins involved in cellular survival/proliferation, namely
      AKT/phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinases
      (MAPKs), and the role of p53 in these processes. ECG induced cell cycle arrest at
      the G0/G1-S phase border associated with the stimulation of p21, p-p53, and p53
      and the suppression of cyclins D1 and B1. Exposure of SW480 cells to ECG also led
      to apoptosis as determined by time-dependent changes in caspase-3 activity, MAPKs
      [extracellular regulated kinase (ERK), p38, and c-jun amino-terminal kinase
      (JNK)], p21 and p53 activation, and AKT inhibition. The presence of pifithrin, an
      inhibitor of p53 function, blocked ECG-induced apoptosis as was manifested by
      restored cell viability and caspase-3 activity to control values and
      reestablished the balance among Bcl-2 anti- and proapoptotic protein levels.
      Interestingly, ECG also inhibited p53 protein and RNA degradation, contributing
      to the stabilization of p53. In addition, JNK and p38 have been identified as
      necessary for ECG-induced apoptosis, upon activation by p53. The results suggest
      that the activation of the p53-p38/JNK cascade is required for ECG-induced cell
      death in SW480 cells. 

PMID- 23859041
TI  - Dietary influence on MAPK-signaling pathways and risk of colon and rectal cancer.
AB  - Mitogen-activated protein kinase (MAPK) pathways regulate cellular functions
      including cell proliferation, differentiation, migration, and apoptosis.
      Associations between genes in the DUSP, ERK1/2, JNK, and p38 MAPK-signaling
      pathways and dietary factors associated with growth factors, inflammation, and
      oxidative stress and risk of colon and rectal cancer were evaluated. Data include
      colon cases (n = 1555) and controls (n = 1956) and rectal cases (n = 754) and
      controls (n = 959). Statistically significant interactions were observed for the
      MAPK-signaling pathways after adjustment for multiple comparisons. DUSP genes
      interacted with carbohydrates, mutagen index, calories, calcium, vitamin D,
      lycopene, dietary fats, folic acid, and selenium. MAPK1, MAPK3, MAPK1, and RAF1
      within the ERK1/2 MAPK-signaling pathway interacted with dietary fats and
      cruciferous vegetables. Within the JNK MAPK-signaling pathway, interactions
      between MAP3K7 and protein, vitamin C, iron, folic acid, carbohydrates, and
      cruciferous vegetables; MAP3K10 and folic acid; MAP3K9 and lutein/zeaxanthin;
      MAPK8 and calcium; MAP3K3 and calcium and lutein; MAP3K1 and cruciferous
      vegetables. Interaction within the p38-signaling pathway included MAPK14 with
      calories, carbohydrates saturated fat, selenium, vitamin C; MAP3K2 and
      carbohydrates, and folic acid. These data suggest that dietary factors involved
      in inflammation and oxidative stress interact with MAPK-signaling genes to alter
      risk of colorectal cancer. 

PMID- 23859042
TI  - Effects of phytoestrogen extracts isolated from pumpkin seeds on estradiol
      production and ER/PR expression in breast cancer and trophoblast tumor cells.
AB  - Phytoestrogens have a controversial effect on hormone-dependent tumours. Herein,
      we investigated the effect of the pumpkin seed extract (PSE) on estradiol
      production and estrogen receptor (ER)-alpha/ER-beta/progesterone receptor (PR)
      status on MCF7, Jeg3, and BeWo cells. The PSE was prepared and analyzed by mass
      spectrometry. MCF7, Jeg3, and BeWo cells were incubated with various
      concentrations of PSE. Untreated cells served as controls. Supernatants were
      tested for estradiol production with an ELISA method. Furthermore, the effect of
      the PSE on ER-alpha/ER-beta/PR expression was assessed by immunocytochemistry.
      The PSE was found to contain both lignans and flavones. Estradiol production was
      elevated in MCF7, BeWo, and Jeg3 cells in a concentration-dependent manner. In
      MCF7 cells, a significant ER-alpha downregulation and a significant PR
      upregulation were observed. The above results after properly designed animal
      studies could highlight a potential role of pumpkin seed's lignans in breast
      cancer prevention and/or treatment. 

PMID- 23859043
TI  - Molecular size fractions of bay leaf (Laurus nobilis) exhibit differentiated
      regulation of colorectal cancer cell growth in vitro.
AB  - Numerous in vitro studies using solvent or aqueous extracts of raw dietary plant
      material have demonstrated modulation of colon cancer cell growth and apoptosis
      and effects on immune and nonimmune pathways of inflammation. We have developed a
      generic, 3-staged food-compatible process involving heating for conversion of
      dietary plants into food ingredients and report results on potential colon cancer
      regulating properties of processed forms of Bay leaf (Laurus nobilis). In vitro
      studies demonstrated inhibition of cancer cell growth by processed Bay leaf
      products in HT-29, HCT-116, Caco-2, and SW-480 human cancer cell lines, which
      were accompanied by variable levels of elevated apoptosis. Bay leaf also exerted
      moderate inhibition of cycloxygenase 2 and 5 lipoxygenase enzymatic activity. In
      addition, these extracts significantly downregulated interferon-gamma production
      in T helper Type 1-stimulated whole blood from healthy donors. Furthermore, size
      fractionation of the extracts revealed that antiproliferative and proapoptotic
      activities were associated with low mass (primarily polyphenolics and essential
      oils) and high mass (primarily proteins including polyphenol oxidase) chemical
      classes, respectively. Bay leaf exerted in vitro bioactivity that might be
      relevant to protecting against early events in sporadic colorectal cancer, with
      potential for further optimization of bioactivity by size-based fractionation. 

PMID- 23859044
TI  - Immunomodulatory activities of Ganoderma sinense polysaccharides in human immune
      cells.
AB  - Medicinal mushrooms have been traditionally used as food nutrient supplements in
      China for thousands of years. The present study aimed to evaluate the
      immunomodulatory activities of Ganoderma sinense (GS), an allied species of G.
      lucidum, using human peripheral blood mononuclear cells (PBMC). Our results
      showed that the polysaccharide-enriched fraction of GS hot water extract (400
      MUg/ml) exhibited significant stimulatory effects on PBMC proliferation. When the
      fruiting bodies of GS were divided into pileus and stipe parts and were
      separately extracted, the GS stipe polysaccharide-enriched fraction (50-400
      MUg/ml) showed concentration-dependent immunostimulating effects in PBMC. The
      productions of tumor necrosis factor-alpha, interleukin (IL)-10, and transforming
      growth factor -beta were significantly enhanced by this fraction. In addition,
      the proportion of CD14(+) monocyte subpopulation within the PBMC was specifically
      increased. The IL-10 and IL-12 productions in monocyte-derived dendritic cells
      were significantly enhanced by GS stipe fraction. The composition of
      monosaccharides of this fraction was determined by ultra performance liquid
      chromatography and ion exchange chromatography. Our study demonstrated for the
      first time the immunostimulatory effects of GS stipe polysaccharide-enriched
      fraction on PBMC and dendritic cells. The findings revealed the potential use of
      GS (especially including the stipes of fruiting bodies) as adjuvant nutrient
      supplements for patients, who are receiving immunosuppressive chemotherapies.

PMID- 23859045
TI  - Evaluation of hydro-alcoholic extract of Eclipta alba for its multidrug
      resistance reversal potential: an in vitro study.
AB  - The development of multidrug resistance (MDR) causes problems in the chemotherapy
      of human cancer. The present study was designed to evaluate and establish the
      role of Eclipta alba as MDR reversal agent using multidrug resistant
      hepatocellular carcinoma cell line (DR-HepG2). To develop DR-HepG2,
      hepatocellular carcinoma cell line (HepG2) was transfected with 2
      Acetylaminofluorene (AAF) and Aflatoxin B1 (AFB). Cytotoxic effects of the
      Eclipta alba hydroalcoholic extract (EAE) and standard anti-ancer drug
      Doxorubicin (DOX) were determined in DR-HepG2 and the parental cells HepG2 using
      MTT assay. The expression level of MDR1 gene and P-glycoprotein (P-gp) level was
      analyzed by RT-PCR and western blotting. From the present investigation, it was
      found that EAE (10 and 20 MUg/ml) could significantly inhibit cell proliferation
      in DR-HepG2 whereas DOX (0.5 MUg/ml) could not because of enhancement effect of
      MDR1/P-gp. This study demonstrated for the first time the antiproliferative
      activities of EAE in multidrug resistant DR-HepG2 cells. The findings revealed
      that Eclipta alba components are effective inhibitors of MDR1/P-gp. 

PMID- 23859046
TI  - Quality, efficiency and integrity: value squeezes in management of hospital
      wards.
AB  - AIM: The aim of this study was to explore and describe the value squeezes
      experienced by ward managers in connection with quality management in hospital
      wards. The study focused on integrity pressure and coping strategies to deal with
      such pressure. BACKGROUND: Nurses in the role of ward managers have a key
      function in the field of quality improvement. These managers are also responsible
      for the efficient running of their wards and thus face tensions between demands
      for both quality and efficiency. METHOD: Data were collected through interviews
      conducted with 10 ward managers from six Norwegian hospitals. The data were
      analysed using both content and template analysis. RESULTS: Ward managers felt
      squeezed between conflicting values associated with demands for both quality and
      efficiency. These tensions resulted in pressure on integrity for the managers as
      well as their nursing colleagues. Three different management strategies were used
      to cope with such pressure: quality conscious, efficiency adjusting and hybrid.
      CONCLUSION: A hybrid strategy appeared to be the best, both for the ward managers
      and the hospital organisations, despite the fragmentation associated with this
      strategy. IMPLICATIONS FOR NURSING MANAGEMENT: Hybrid management may be
      beneficial for coping with pressure on integrity, although more empirical
      research is needed.

PMID- 23859047
TI  - Autologous islet transplantation after total pancreatectomy for renal cell
      carcinoma metastases.
AB  - Pancreatic metastases from renal cell carcinoma (RCC) may have a chronic and
      highly indolent course, and may be resected for cure after considerable delay
      following treatment of the primary tumor, in contrast to other more common
      pancreatic tumors. Surgical resection is the treatment of choice, which may lead
      to postpancreatectomy diabetes mellitus in the case of extensive resection. We
      present a 70-year-old patient with multifocal pancreatic metastases from RCC
      causing obstructive jaundice. A total pancreatectomy was required to excise two
      distant tumors in the head and tail of the pancreas, together with a segment VI
      liver resection. An autologous islet transplant (AIT) prepared from the central,
      uninvolved pancreas was carried out to prevent postpancreatectomy diabetes. The
      patient was rendered insulin-free and remains so with excellent glycemic control
      for 1 year of follow-up, and there is no evidence of tumor recurrence. The
      patient has been treated with adjuvant sunitinib to minimize risk of further
      recurrence. In conclusion, AIT after pancreatectomy may represent a useful option
      to treat patients with metastatic RCC. A critical component of this approach was
      dependent upon elaborate additional testing to exclude contamination of the islet
      preparation by cancerous cells.

PMID- 23859048
TI  - Is the WISC-IV General Ability Index a useful tool for identifying intellectual
      disability?

PMID- 23859050
TI  - Complete mitochondrial genome of the Critically Endangered speartooth shark
      Glyphis glyphis (Carcharhiniformes: Carcharhinidae).
AB  - In this study we present the first complete mitogenome for the speartooth shark
      Glyphis glyphis, a rare euryhaline elasmobranch from northern Australia and Papua
      New Guinea. The mitogenome is 16,702 bp in length and the overall base
      composition is 31.5% A; 26.0% C; 13.0% G and 29.5% T. It includes 2 ribosomal RNA
      (rRNA) genes, 22 transfer RNA (tRNA) genes, 13 protein-coding genes and a
      putative 1066 bp long control region. The COI gene is initiated by GTG codon
      whereas the remaining protein-coding genes started with the ATG codon. This study
      will help elucidate the taxonomy of this poorly known group of sharks.

PMID- 23859051
TI  - Genetic diversity and population structure of largehead hairtail, Trichiurus
      japonicus, based on mtDNA control region.
AB  - Largehead hairtail, Trichiurus japonicus, is a valuable commercially exploited
      demersal species. We gathered mtDNA control region sequences (3' mtDNA CR) of T.
      japonicus to investigate its genetic diversity and population genetic structure.
      Fifty-four specimens were collected from the nearshore localities along the
      coastline of China. A total of 42 polymorphic sites were found, which defined 40
      haplotypes. A pattern with high level of haplotype diversity (h = 0.98 +/- 0.01)
      and very low level of nucleotide diversity (pi = 0.008 +/- 0.005) were detected
      in the examined range. Comparing pi with other fish species shows that T.
      japonicus has remarkable low genetic diversity values compared with other Pacific
      Ocean marine fishes. AMOVA and conventional Fst values revealed no significant
      genetic structure throughout the examined range, which is inconsistent with the
      previous findings based on the morphological and ecological studies. Using a
      variety of phylogenetic methods, coalescent reasoning, and molecular dating
      interpreted in conjunction with paleoclimateic and physiographic evidence, we
      infer that the genetic make-up of extant populations of T. japonicus was shaped
      by Pleistocene environmental impacts on the historical demography of this
      species. Coalescent analyses (Neutrality tests, Mismatch distribution analysis,
      Bayesian skyline analyses) showed that the species along the coastline of China
      has experienced population expansions originated in its most recent history at
      about 153-216 kyr.

PMID- 23859052
TI  - Complete mitochondrial genome of sea urchin: Hemicentrotus pulcherrimus
      (Camarodonta, Strongylocentrotidae).
AB  - The complete mitochondrial genome of sea urchin Hemicentrotus pulcherrimus (A.
      Agassiz, 1863) is determined. The genome is a circular molecule of 15,705 bp in
      length and the gene content and order are identical to those of other
      strongylocentrotid species. Lengths of all protein coding genes (PCGs) are
      identical to those of M. nudus. S. droebachiensis and S. pallidus but ND6 has a
      deletion of 3 amino acids at the C-terminal. The nucleotide composition of the
      genome shows a bias toward A + T (59.8%) and the A + T bias in PCGs (59.4%) is
      slightly higher than the other strongylocentrotid species. The mitogenome of H.
      pulcherrimus provides genomic information of the single species genus,
      Hemicentrotus and helps understand the genetic relationship and the evolution of
      the genus in relation to the other genera of the family Strongylocentrotidae.

PMID- 23859053
TI  - Mitochondrial genome of Protobothrops maolanensis (Squamata: Viperidae:
      Crotalinae).
AB  - Protobothrops maolanensis was recently described from Guizhou, southwestern
      China. In this study, the complete mitochondrial genome of P. maolanensis had
      been determined. The circle genome with the 17,231 bp total length contained 13
      protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 control
      regions. Overall, base composition of the complete mtDNA was 32.96% A, 24.92% T,
      29.41% C and 12.72% G. All the genes in P. maolanensis were distributed on the H
      strand, except for the ND6 subunit gene and eight tRNA genes which were encoded
      on the L-strand.

PMID- 23859054
TI  - Complete mitochondrial genome of Neochauliodes bowringi (MacLachlan)
      (Megaloptera: Corydalidae).
AB  - We describe and analyze the complete mitochondrial genome of Neochauliodes
      bowringi (MacLachlan) (Megaloptera: Corydalidae). The length of the genome is
      16,064 bp (GenBank accession No. JQ351950), the longest mitochondrial genome in
      the order Megaloptera already got, which includes 22 transfer RNA genes, 13
      protein-coding genes, two ribosomal RNAs and an A + T-rich region. The gene
      arrangement is similar to that of Drosophila yakuba, the presumed ancestral
      insect mitochondrial gene arrangement. All protein-coding genes start with ATN
      start codon except for the gene ND4, which uses GTG as start codon. Eight protein
      coding genes use TAA as stop codon and others use incomplete stop codons "T" or
      "TA". The A + T-rich region is located between rrnS and trnI with a length of
      1328 bp.

PMID- 23859055
TI  - Effect of novel dinuclear platinum(II) complexes on redox status of MOLT-4
      leukemic cells.
AB  - As the alkylating agents metabolism is accompanied by reactive oxygen species
      (ROS) generation, the aim of this study has been to compare the effect of
      cisplatin and novel platinum(II) complexes, Pt2(isopropylamine)4(berenil)2,
      Pt2(piperazine)4(berenil)2, Pt2(2-picoline)4(berenil)2, Pt2(3
      picoline)4(berenil)2, Pt2(4-picoline)4(berenil)2, on the redox state of human
      leukemic T-cells line Molt-4. Treatment of Molt-4 with the novel complexes has
      shown that all compounds enhance total ROS and superoxide anion generation as
      well as change the activity of antioxidant enzymes such as superoxide dismutase,
      catalase, glutathione peroxidase and glutathione reductase. Moreover, all the
      above-mentioned compounds cause a decrease in the level of non-enzymatic
      antioxidants such as GSH as well as vitamin C, E and A. Such a situation is
      conducive to oxidative stress formation and oxidative modifications of cellular
      macromolecules. DNA damage of MOLT-4 leukemic cells is connected with 8-hydroxy
      2'-deoxyguanosine and N7-methyldeoxyguanosine generation. The increased level of
      protein carbonyl groups and dityrosine indicates enhanced protein oxidative
      modifications, while an increase in the level of lipid peroxidation products,
      MDA, 4-HNE and isoprostanes proves the significant lipid peroxidation after
      treatment of Molt-4 cells with the complexes. Moreover, the complexes enhance
      expression of Bax and cytochrome c as well as decrease the expression of Bcl-2
      and p53 protein. The novel platinum(II) complexes in comparison with cisplatin
      disturb redox status more intensively and lead to oxidative stress in Molt-4
      cells. The enhanced oxidative modifications of macromolecules of human leukemic
      cancer cells lead to a shift in the proapoptotic-antiapoptotic balance into the
      proapoptotic direction.

PMID- 23859056
TI  - Clinical and radiological outcomes in 153 patients undergoing oblique corpectomy
      for cervical spondylotic myelopathy.
AB  - OBJECTIVE: To document the clinical and radiological outcomes in a large series
      of patients undergoing the oblique cervical corpectomy (OCC) for spondylotic
      myelopathy. MATERIALS AND METHODS: We retrospectively analyzed our series of 153
      patients undergoing OCC for cervical spondylotic myelopathy (CSM) over the last
      10 years. A mean clinical follow-up of 3 years was obtained in 125 patients
      (81.7%), while 117 patients (76.5%) were followed up radiologically. Neurological
      function was measured by the Nurick grade and the modified Japanese Orthopedic
      Association score (JOA). Plain radiographs and magnetic resonance images (MRI)
      were reviewed. RESULTS: Ninety-two percent were men with a mean age of 51 years
      and a mean duration of symptoms of 18 months. Sixty-one had a single level
      corpectomy, 66 had a 2-level, 24 had a 3-level, and two had a 4-level OCC. There
      was statistically significant improvement (p < 0.05) in both the Nurick grade and
      the JOA score at mean follow-up of 34.6 +/- 25.4 months. Permanent Horner's
      syndrome was seen in nine patients (5.9%), postoperative C5 radiculopathy in five
      patients (3.3%), dural tear with CSF leak in one patient (0.7%), and vertebral
      artery injury in one patient (0.7%). Of the 117 patients who were followed up
      radiologically, five patients (4.3%) developed an asymptomatic kyphosis of the
      cervical spine while 22 patients (25.6%) with preoperative lordotic spines had a
      straightening of the whole spine curvature. CONCLUSIONS: The OCC is a safe
      procedure with good outcomes and a low morbidity for treating cervical cord
      compression due to CSM. This procedure avoids graft-related complications
      associated with the central corpectomy, but is technically demanding.

PMID- 23859058
TI  - Preliminary comparison of bone-anchored hearing instruments and a dental device
      as treatments for unilateral hearing loss.
AB  - OBJECTIVE: To compare the effectiveness of two types of treatment for unilateral
      hearing loss (UHL), bone-anchored hearing instruments (BAHI) and a dental device
      (SoundBite). DESIGN: Either BAHI or SoundBite were worn for 30 days, and then the
      devices were swapped and the second device was worn for 30 days. Measures
      included unaided and aided sound-field thresholds, sound localization, and
      perception of speech in babble. The APHAB questionnaire was administered for each
      trial period. STUDY SAMPLE: Nine adult BAHI wearers with UHL. RESULTS: Mid
      frequency aided thresholds were lower for SoundBite than for BAHI. Both devices
      gave benefits for localization after 30 days, but there was no difference between
      devices. Speech perception was better for both devices than for unaided listening
      when the target speech came from the poorer hearing side or in front, and the
      interfering babble came from the better-hearing side. There was no consistent
      difference between devices. APHAB scores were better for SoundBite than for BAHI.
      CONCLUSIONS: Speech perception and sound localization were similar for the two
      types of device, but the SoundBite led to lower aided thresholds and better APHAB
      scores than the BAHI.

PMID- 23859059
TI  - Prescription of hearing-aid output for tinnitus relief.
AB  - OBJECTIVE: Tinnitus is a perceived sound that cannot be attributed to an external
      source. This study attempts to identify a prescription of amplification that is
      optimized as a first-fit setting for tinnitus relief. DESIGN: Participants
      compared the effect of high frequency amplification on their tinnitus. Stimuli
      were 13 speech files with different amounts of high frequency amplification
      (three cut-off frequencies and four gain settings) to simulate the effects of a
      change in DSL(I/O) v5.0 prescription in the high frequencies. STUDY SAMPLE:
      Twenty-five participants with chronic tinnitus participated in the study.
      RESULTS: A 6-dB reduction to prescribed gain at 2 kHz emerged as the most
      preferred output (26.47% participants) to interfere with participants' tinnitus.
      Overall, 70.58% of the participants' preferred a 3 to 6 dB reduction in output
      while 29.42% preferred a similar increase across all cut-off frequencies. A trend
      was observed in which the higher the tinnitus pitch the more similar the
      preferred output to DSL(I/O) v5.0. CONCLUSION: DSL(I/O) v5.0 appears to be a good
      starting point for prescription of hearing-aid output for tinnitus management.
      Long-term benefits of different prescriptions for tinnitus still need to be
      ascertained.

PMID- 23859060
TI  - Audiometric thresholds and portable digital audio player user listening habits.
AB  - OBJECTIVE: To examine the relationship between portable digital audio player
      listening behaviours and (1) measured sound pressure levels, (2) audiometric
      measures, (3) self-reported hearing loss symptoms. DESIGN: A questionnaire to
      evaluate listening behaviours, including self-reported hearing loss symptoms and
      listening duration/volume settings. Multivariate regression analysis was used to
      determine the relationship between these variables, audiometric evaluation,
      calculated exposure levels, Lex(8hr), and measured sound pressure levels,
      Leq(32sec). STUDY SAMPLE: This study included 103 males and 134 female subjects
      aged 10 to 17 years. RESULTS: Calculated Lex(8hr) and measured Leq(32sec) levels
      increased with age and self-reported usage time. Audiometric thresholds averaged
      over 4 and 8 kHz were higher when usage exceeded five years as compared to less
      than one year. Higher measured sound pressure levels were associated with worse
      audiometric thresholds at (0.5, 1, 2 kHz, averaged) and 4 kHz. Self-reported
      hearing loss symptoms were reported by 33% to 50% of subjects. CONCLUSIONS: In
      this cohort sample, our results support a statistical association between hearing
      acuity and (1) Self-reported weekly usage in hours; (2) Tightness of fit; (3)
      Years of usage; and (4) Measured sound pressure levels. Generalizing these
      results beyond the current sample would require additional research.

PMID- 23859061
TI  - Update on Alzheimer's disease therapeutics.
AB  - Alzheimer's disease (AD) is the leading cause of dementia worldwide. Clinically,
      it is characterized by progressive cognitive impairment and the emergence of
      neuropsychiatric disturbances. In recent years, many drug candidates aimed at
      disease modification have advanced into large, randomized controlled trials, but
      none have demonstrated efficacy in slowing down the relentless progression of AD.
      While the exact cause of AD is still being fervently investigated, the field is
      moving toward earlier identification and treatment of the disease, as it is
      believed this may be the main reason for so many clinical trial failures. There
      are currently four main mechanisms of action that are being actively developed in
      AD therapeutics: Drugs aimed at reducing Abeta production, notably secretase
      inhibitors; Drugs aimed at reducing Abeta plaque burden via inhibition of
      aggregatio or disruption of aggregates; Drugs aimed at promoting Abeta clearance
      via active or passive immunotherapy; and Drugs aimed at preventing tau protein
      phosphorylation. In this review, recent findings from clinical and preclinical
      studies in each of these categories will be discussed, as well as a category
      entitled ' other therapies,' that includes treatments that do not fit under a
      single mechanism of action, but represent rational interventions for the
      underlying pathology of Alzheimer's disease. 

PMID- 23859062
TI  - Diversity of the spinach (Spinacia oleracea) spermosphere and phyllosphere
      bacterial communities.
AB  - The bacterial diversity of seeds, transmission of bacteria from seed to
      phyllosphere, and fate of seed-transmitted bacteria on mature plants are poorly
      characterized. Understanding the dynamics of microbial communities is important
      for finding bio-control or mitigation strategies for human and plant pathogens.
      Bacterial populations colonizing spermosphere and phyllosphere of spinach
      (Spinacia oleracea) seedlings and plants were characterized using pyrosequencing
      of 16S rRNA gene amplicons. Spinach seed microbiota was composed of three
      bacterial phyla: Proteobacteria, Firmicutes and Actinobacteria, belonging to >
      250 different operational taxonomic units (OTUs). Seed and cotyledon bacterial
      communities were similar in richness and diversity. Richness of 3-4 leaf-stage of
      development plants increased markedly to > 850 OTUs classified within 11 phyla.
      Although some bacterial OTUs were detected on seeds, cotyledons and plants, the
      breadth of new sequences indicates the importance of multiple sources outside the
      seed in shaping phyllosphere community. Most classified sequences were from
      previously undescribed taxa, highlighting the benefits of pyrosequencing in
      describing seed diversity and phyllosphere bacterial communities. Bacterial
      community richness increased from 250 different OTUs for spinach seeds and
      cotyledons, to 800 OTUs for seedlings. To our knowledge this is the first
      comprehensive characterization of the spinach microbiome, complementing previous
      culture-based and clone library studies. 

PMID- 23859063
TI  - Formal syntheses of (+/-)-platensimycin and (+/-)-platencin via a dual-mode Lewis
      acid induced cascade cyclization approach.
AB  - A mild and efficient dual-mode Lewis acid induced Diels-Alder
      (DA)/carbocyclization cascade cyclization reaction has been developed for
      construction of the tricyclic core of ent-kaurenoids in one pot with the aid of a
      theoretical study on the pi,sigma-Lewis acidities of a variety of Lewis acids.
      With ZnBr2 as the dual-mode Lewis acid, a series of substituted enones and dienes
      underwent DA/carbocyclization cascade cyclization reaction smoothly at room
      temperature and provided the tricyclic cyclized products in one pot with good
      yields and high diastereoselectivity. The tricyclic cyclized product has been
      successfully utilized as a common intermediate for formal syntheses of (+/-)
      platensimycin and (+/-)-platencin. 

PMID- 23859064
TI  - Application of a global reference for fetal-weight and birthweight percentiles in
      predicting infant mortality.
AB  - OBJECTIVE: To determine whether the recently published A global reference for
      fetal-weight and birthweight percentiles (Global Reference) improves small-
      (SGA), appropriate- (AGA), and large-for-gestational-age (LGA) definitions in
      predicting infant mortality. DESIGN: Population-based cohort study. SETTING: The
      US Linked Livebirth and Infant Death records between 1995 and 2004. POPULATION:
      Singleton births with birthweight >500 g born at 24-41 weeks of gestation.
      METHODS: We compared infant mortality rates of SGA, AGA, and LGA infants
      classified by three different references: the Global Reference; a commonly used
      birthweight reference; and Hadlock's ultrasound reference. MAIN OUTCOME MEASURES:
      Infant mortality rates. RESULTS: Among 33 997 719 eligible liveborn singleton
      births, 25% of preterm and 9% of term infants were classified differently for
      SGA, AGA, and LGA by the Global Reference and the birthweight reference. The
      Global Reference indicated higher mortality rates in preterm SGA and preterm LGA
      infants than the birthweight reference. The mortality rate was considerably
      higher in infants classified as preterm SGA by the Global Reference but not by
      the birthweight reference, compared with the corresponding infants classified by
      the birthweight reference but not by the Global Reference (105.7 versus 12.9 per
      1000, RR 8.17, 95% CI 7.38-9.06). Yet, the differences in mortality rates were
      much smaller in term infants than in preterm infants. Black infants had a
      particularly higher mortality rate than other races in AGA and LGA preterm and
      term infants. CONCLUSIONS: In respect to the commonly used birthweight reference,
      the Global Reference increases the identification of infant deaths by improved
      classification of abnormal newborn size at birth, and these advantages were more
      obvious in preterm than in term infants.

PMID- 23859065
TI  - Covalent adduction of nitrogen mustards to model protein nucleophiles.
AB  - Protein adducts have the potential to serve as unique biomarkers of exposure to
      compounds of interest. Many xenobiotics (or their metabolites) are electrophilic
      and therefore reactive with nucleophilic amino acid residues on proteins.
      Nitrogen mustards are reactive xenobiotics with potential use as chemical warfare
      agents (CWA) or agents of terrorist attack, in addition to being employed as
      chemotherapeutic agents. The present study utilized cysteine-, lysine-, and
      histidine-containing model peptides to characterize in vitro adduction of the
      nitrogen mustards mechloroethamine (HN-2) and tris-(2-chlorethyl)amine (HN-3) to
      these nucleophilic amino acid residues by means of liquid chromatography-tandem
      mass spectrometry. The study assessed the structure of adducts formed, the time
      course of adduct formation, concentration-response relationships, and temporal
      stability of adducts. Adduction was hypothesized to occur on all three model
      peptides via initial formation of a reactive aziridinium intermediate for both
      mechloroethamine and tris-(2-chlorethyl)amine, followed by covalent adduction to
      nucleophilic residues. While adduction was found to occur most readily with
      cysteine, it was also observed at lysine and histidine, demonstrating that
      adduction by mechloroethamine and tris-(2-chlorethyl)amine is possible at
      multiple nucleophilic sites. Following solid phase extraction cleanup, adducts
      formed with mechloroethamine were stable for up to three weeks. Adducts formed
      with tris-(2-chlorethyl)amine were less stable; however, hydrolyzed secondary
      adducts were observed throughout the three week period. This study demonstrates
      that the nitrogen mustards mechloroethamine and tris-(2-chlorethyl)amine form
      stable adducts with reactive protein nucleophiles other than cysteine. 

PMID- 23859066
TI  - Predictive value of T-cell clone and CD13 antigen in parapsoriasis.

PMID- 23859067
TI  - Atrophy and hypertrophy following injections of botulinum toxin in children with
      cerebral palsy.

PMID- 23859069
TI  - 'Stigma: the cul-de-sac of the double bind' the perspective of Turkiye; a
      phenomenological study.
AB  - The aim of this study was to explore and describe the stigmatization experienced
      by individuals with mental health problems (IMHP) and the relationships between
      stigmas associated with mental health problems, psychiatric diagnoses,
      treatments, and social environments and their consequences. Thirty-three IMHP
      were recruited from outpatient and day clinics at the psychiatry department of a
      university hospital within a 5-month time period for this qualitative,
      descriptive study. Data were gathered using a structured interview form with open
      ended questions to explore the changes in everyday life experienced by IMHP
      during the course of their illness. Data were analysed using the Colaizzi method
      of analysis. Our findings show that almost all IMHP were concerned about being
      stigmatized by others, society, their family, and health care professionals.
      Another concern that IMHP reported was self-stigmatization. Stigmatization serves
      as a barrier to treatment adherence and socialization in IMHP. Furthermore,
      stigmatization has a significant impact on the lives of IMHP, and methods of
      coping with stigmatization are commonly ineffective. However, stigmatization can
      be reduced by dealing with the illness, IMHP, their relatives, and professionals
      in an unprejudiced manner.

PMID- 23859070
TI  - Naphthalene carbohydrazone based dizinc(II) chemosensor for a pyrophosphate ion
      and its DNA assessment application in polymerase chain reaction products.
AB  - A new naphthalene carbohydrazone based dizinc(II) complex has been synthesized
      and investigated to act as a highly selective fluorescence and visual sensor for
      a pyrophosphate ion with a quite low detection limit of 155 ppb; this has also
      been used to detect the pyrophosphate ion released from polymerase-chain
      reaction. 

PMID- 23859071
TI  - Investigation of PNPLA3 and IL28B genotypes on diabetes and obesity after liver
      transplantation: insight into mechanisms of disease.
AB  - To identify genetic risks for obesity and diabetes postliver transplantation
      (LT), LT recipients underwent genotyping for IL28B rs12979860 (n = 295) and
      PNPLA3 rs738409 (n = 205) polymorphism in both donors and recipients. The
      development of obesity and diabetes/impaired fasting glucose (IFG) was determined
      1-5 years post-LT. Recipient PNPLA-3 genotype was independently associated with
      obesity (BMI > 30) at 3 years posttransplant (genotype CC 33.7%, CG 48.3% and GG
      82.4%, p = 0.002), with an odds ratio (OR 2.54, CI 1.38-4.66, p = 0.003),
      associated with the G allele. Diabetes/IFG diagnosed within 5 years
      posttransplant associated with PNPLA-3 non-CC genotype (HR 1.59, 1.12-2.26, p =
      0.010), but not IL28B TT genotype (HR 1.46, 0.94-2.27, p = 0.092). No genotype
      variable was independently predictive of diabetes/IFG. The combination of PNPLA-3
      non-CC and IL28B TT genotype was associated with increased risk of diabetes/IFG
      compared to PNPLA-3 CC, IL28B non-TT (HR 2.64, CI 1.30-5.39, p = 0.008). Donor
      genotypes were not associated with any of the outcomes analyzed. In conclusion,
      PNPLA-3 non-CC genotype is associated with posttransplant obesity but not
      independently with diabetes/IFG. The lack of donor related risk suggests a
      peripheral rather than central mechanism of insulin resistance in liver
      transplant recipients.

PMID- 23859072
TI  - A robust molecular porous material with high CO2 uptake and selectivity.
AB  - We report MPM-1-TIFSIX, a molecular porous material (MPM) based upon the neutral
      metal complex [Cu2(adenine)4(TiF6)2], that self-assembles through a hydrogen
      bonding network. This MPM is amenable to room-temperature synthesis and
      activation. Gas adsorption measurements and ideal adsorbed solution theory
      selectivity predictions at 298 K revealed enhanced CO2 separation performance
      relative to a previously known variant as well as the highest CO2 uptake and
      isosteric heat of adsorption yet reported for an MPM. MPM-1-TIFSIX is thermally
      stable to 568 K and retains porosity and capacity even after immersion in water
      for 24 h. 

PMID- 23859073
TI  - Dissociation-based screening of nanoparticle-protein interaction via flow field
      flow fractionation.
AB  - A protein corona will be formed on nanoparticles (NPs) entering a biological
      matrix, which can influence particles' subsequent behaviors inside the biological
      systems. For proteins bound stably to the NPs, they can exhibit different
      association/dissociation rates. The binding kinetics could affect interaction of
      the NPs with cell surface receptors and possibly contribute to the outcomes of
      NPs uptake. In the present study, a method to differentiate the corona proteins
      based on their relative dissociation rates from the NPs was developed, employing
      flow field-flow fraction (F4) in combination with centrifugation. The proteins
      bound to the superparamagnetic iron oxide NPs (SPION) present in an IgG/albumin
      depleted serum were isolated via collection of the SPIONs by either F4 or
      centrifugation. They were subsequently analyzed by LC-MS/MS and identified.
      Because the SPION-protein complexes injected to F4 dissociated continuously under
      the nonequilibrium separation condition, only the proteins with slow enough
      dissociation rates would be collected with the NPs in the eluent of F4. However,
      in centrifugation, proteins with good affinity to the SPIONs were collected
      regardless of the dissociation rates of the complexes. In both cases, the
      nonbinding ones were washed off. Capillary electrophoresis and circular dichroism
      were employed to verify the binding situations of a few SPION-protein
      interactions, confirming the effectiveness of our method. Our results support
      that our method can screen for proteins binding to NPs with fast on-and-off
      rates, which should be the ones quickly exchanging with the free matrix proteins
      when the NPs are exposed to a new biological media. Thus, our method will be
      useful for investigation of the temporal profile of protein corona and its
      evolution in biological matrices as well as for high-throughput analysis of the
      dynamic feature of protein corona related to particle properties. 

PMID- 23859074
TI  - Toxoflavins and deazaflavins as the first reported selective small molecule
      inhibitors of tyrosyl-DNA phosphodiesterase II.
AB  - The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been
      implicated in the topoisomerase-mediated repair of DNA damage. In the clinical
      setting, it has been hypothesized that TDP2 may mediate drug resistance to
      topoisomerase II (topo II) inhibition by etoposide. Therefore, selective
      pharmacological inhibition of TDP2 is proposed as a novel approach to overcome
      intrinsic or acquired resistance to topo II-targeted drug therapy. Following a
      high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were
      identified as the first reported sub-micromolar and selective inhibitors of this
      enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity
      relationship (SAR) for TDP2 enzymatic inhibition. However, we observed a key
      redox liability of this series, and this, alongside early in vitro drug
      metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The
      deazaflavins were developed from a singleton HTS hit. This series showed distinct
      SAR and did not display redox activity; however low cell permeability proved to
      be a challenge. 

PMID- 23859075
TI  - Spiritual needs and spiritual support preferences of people with end-stage heart
      failure and their carers: implications for nurse managers.
AB  - BACKGROUND: Spiritual care is an important element of holistic care but has
      received little attention within palliative care in end-stage heart failure.
      AIMS: To identify the spiritual needs and spiritual support preferences of end
      stage heart failure patients/carers and to develop spiritual support guidelines
      locally. METHOD: Semi-structured interviews (totalling 47) at 3-monthly intervals
      up to 1 year with 16 end-stage heart failure patients/carers. Focus
      group/consultation with stakeholders. RESULTS: Participants were struggling with
      spiritual/existential concerns alongside the physical and emotional challenges of
      their illness. These related to: love/belonging; hope; coping; meaning/purpose;
      faith/belief; and the future. As a patient's condition deteriorated, the emphasis
      shifted from 'fighting' the illness to making the most of the time left.
      Spiritual concerns could have been addressed by: having someone to talk to;
      supporting carers; and staff showing sensitivity/taking care to foster hope. A
      spiritual support home visiting service would be valued. CONCLUSIONS: Our sample
      experienced significant spiritual needs and would have welcomed spiritual care
      within the palliative care package. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse
      managers could play a key role in developing this service and in leading further
      research to evaluate the provision of such a service in terms of its value to
      patients and other benefits including improved quality of life, spiritual
      wellbeing, reduced loneliness/isolation and a possible reduction in hospital
      admissions.

PMID- 23859076
TI  - Tunable electronics in large-area atomic layers of boron-nitrogen-carbon.
AB  - We report on the low-temperature electrical transport properties of large area
      boron and nitrogen codoped graphene layers (BNC). The temperature dependence of
      resistivity (5 K < T < 400 K) of BNC layers show semiconducting nature and
      display a band gap which increases with B and N content, in sharp contrast to
      large area graphene layers, which shows metallic behavior. Our investigations
      show that the amount of B dominates the semiconducting nature of the BNC layers.
      This experimental observations agree with the density functional theory (DFT)
      calculations performed on BNC structures similar in composition to the
      experimentally measured samples. In addition, the temperature dependence of the
      electrical conductivity of these samples displays two regimes: at higher
      temperatures, the doped samples display an Arrhenius-like temperature dependence
      thus indicating a well-defined band gap. At the lowest temperatures, the
      temperature dependence of the conductivity deviates from activated behavior and
      displays a conduction mechanism consistent with Mott's two-dimensional (2D)
      variable range hopping (2D-VRH). The ability to tune the electronic properties of
      thin layers of BNC by simply varying the concentration of B and N will provide a
      tremendous boost for obtaining materials with tunable electronic properties
      relevant to applications in solid state electronics. 

PMID- 23859077
TI  - A collagen-targeted biomimetic RGD peptide to promote osteogenesis.
AB  - Osteogenesis is a complex, multifactorial process in which many different signals
      interact. The bone morphogenetic proteins (BMPs) are the most potent inducers of
      osteoblastic differentiation, although very high doses of BMPs in combination
      with collagen type I formulations have to be used for clinical applications.
      Although integrin-binding arginine-glycine-aspartic acid (RGD) biomimetic
      peptides have shown some promising abilities to promote the attachment of cells
      to biomaterials and to direct their differentiation, the linking of these
      peptides to collagen sponges usually implies chemical manipulation steps. In this
      study, we describe the design and characterization of a synthetic collagen
      targeted RGD biomimetic (CBD-RGD) peptide formed from a collagen-binding domain
      derived from the von Willebrand factor and the integrin-binding RGD sequence.
      This peptide was demonstrated to bind to absorbable collagen type I sponges
      (ACSs) without performing any chemical linking, and to induce the differentiation
      of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem
      cells. Furthermore, in vivo experiments showed that ACSs functionalized with CBD
      RGD and loaded with a subfunctional dose of BMP-2-formed ectopic bone in rats,
      while nonfunctionalized sponges loaded with the same amount of BMP-2 did not.
      These results indicate that the combination of this biomimetic peptide with the
      currently used collagen+BMP system might be a promising approach to improve
      osteogenesis and to reduce the doses of BMPs needed in clinical orthopedics. 

PMID- 23859078
TI  - Metalloprotease genes of Trichophyton mentagrophytes are important for
      pathogenicity.
AB  - Metalloproteases (Mep) of the M36 family are important virulence factors for the
      host invasion by the dermatophyte Trichophyton mentagrophytes. Dermatophytes
      secrete keratinase to degrade human and animal keratin and invade the skin. In
      previous studies, primers designed from the MEP gene sequences of Aspergillus
      fumigatus and A. oryzae were used to amplify the MEP genes from T.
      mentagrophytes, and the five MEP genes (MEP1-MEP5) were expressed. Differences in
      the expression of these five MEP genes in different dermatophytes were observed
      in an in vitro protein induction study, indicating their different functions and
      proteolytic abilities. However, specific pathogenic functions and mechanisms of
      each of the metalloproteases, as well as differences in their proteolytic
      activities, remain uncertain. In the current study, Agrobacterium tumefaciens
      mediated transformation (ATMT) was used to successfully transform five MEP genes,
      resulting in five MEP mutant strains. MEP3 showed strongest proteolytic activity,
      hair biodegradation ability, and animal pathogenicity among the mutant strains.
      The MEP4 and MEP5 mutants were the least pathogenic through the above tests.
      Therefore, we hypothesize that the MEP4 and MEP5 genes are most likely to
      significantly affect the pathogenicity of T. mentagrophytes. 

PMID- 23859079
TI  - Antioxidative and immunogenic properties of catalase-peroxidase protein in
      Penicillium marneffei.
AB  - Penicillium marneffei is a significant opportunistic fungal pathogen in Southeast
      Asia and its ability to survive inside the host macrophages is believed to be
      important in the establishment of infection. Previously, we isolated a gene
      encoding a catalase- peroxidase (cpeA) from P. marneffei and showed that the cpeA
      transcript is specifically upregulated during yeast phase growth at 37  degrees
      C. In this study, the cpeA transcript was found to be induced during the mycelium
      to yeast phase transition and during stress conditions induced by hydrogen
      peroxide treatment. Null mutation of cpeA reduced the fungal tolerance to
      hydrogen peroxide but not to heat stress. These results indicated that the CpeA
      plays a crucial role in this fungus' oxidative stress response. Western blot
      analysis demonstrated that the CpeA induced antibody production in P. marneffei
      infected patients, including highly exposed-healthy people. This is the first
      report that the catalase-peroxidase possesses an immunogenic property in fungi.

PMID- 23859080
TI  - Detection of Pneumocystis infections by in situ  hybridization in lung samples of
      Austrian pigs  with interstitial pneumonia.
AB  - Pneumocystis carinii f. sp. suis is a fungus multiplying in the respiratory tract
      of pigs which occasionally is associated with interstitial pneumonia.
      Identification of Pneumocystis in tissue samples is considered difficult and
      there are only scarce data on its occurrence in European pigs. This investigation
      presents an in situ hybridization (ISH) procedure for identification of
      Pneumocystis spp. in paraffin wax embedded tissue samples and its application for
      labeling the agent in lung samples of pigs with interstitial pneumonia. Thirty
      two out of 100 lung samples from pigs on Austrian farms were identified as
      positive, five of them with multiple, 12 with moderate and 15 with few organisms
      but Grocott's methenamine silver staining demonstrated that only 20 cases were
      unequivocally positive for Pneumocystis carinii. In addition to interstitial
      pneumonia Pneumocystis-positive pigs were more frequently affected with
      granulomatous pneumonia than Pneumocystis-negative pigs. Frequently concurrent
      infections with different viral or bacterial lung pathogens were noted but there
      was no positive correlation between Pneumocystis- and PCV-2-infections. With
      other infections, no clear-cut differences between Pneumocystis-positive and
      Pneumocystis-negative animals were found. This study shows that Pneumocystis
      infections occur frequently in Austrian pigs with interstitial pneumonia. It
      remains to be shown which are the factors triggering severe multiplication and
      whether infection with Pneumocystis alone is able to induce lung disease in pigs.

PMID- 23859081
TI  - Short-term effects of fine particulate air pollution on emergency room visits for
      cardiac arrhythmias: a case-crossover study in Taipei.
AB  - This study was undertaken to determine whether there was an association between
      fine particles (PM2.5) levels and number of emergency room (ER) visits for
      cardiac arrhythmias in Taipei, Taiwan. ER visits for cardiac arrhythmias and
      ambient air pollution data for Taipei were obtained for the period 2006-2010. The
      relative risk (RR) of ER visits was estimated using a case-crossover approach,
      controlling for weather variables, day of the week, seasonality, and long-term
      time trends. For the single-pollutant model (without adjustment for other
      pollutants), increased numbers of ER cardiac arrhythmia visits were significantly
      associated with PM2.5 on both warm days (>23 degrees C) and cool days (< 23
      degrees C), with an interquartile range rise associated with a 10% (95% CI = 
      15%) and 4% (95% CI = 0-8%) elevation in number of ER visits for cardiac
      arrhythmias, respectively. In the two-pollutant models, PM2.5 levels remained
      significant after inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm
      and cool days. This study provides evidence that higher levels of PM2.5 increase
      the risk of number of ER visits for cardiac arrhythmias.

PMID- 23859082
TI  - Additional information from chromosomal microarray analysis (CMA) over
      conventional karyotyping when diagnosing chromosomal abnormalities in
      miscarriage: a systematic review and meta-analysis.
AB  - BACKGROUND: Approximately 50% of spontaneous miscarriages are associated with
      chromosome abnormalities. Identification of these karyotypic abnormalities helps
      to estimate recurrence risks in future pregnancies. Chromosomal microarray
      analysis (CMA) is transforming clinical cytogenetic practice with its ability to
      examine the human genome at increasingly high resolution. OBJECTIVES: The aim of
      this study was to determine whether CMA testing on the products of conception
      following miscarriage provides better diagnostic information compared with
      conventional karyotyping. SEARCH STRATEGY: MEDLINE (from 1996 to December 2012),
      EMBASE (from 1974 to December 2012), and CINAHL (from 1996 to December 2012)
      databases were searched electronically. SELECTION CRITERIA: Studies were selected
      if CMA was used on products of conception following miscarriage, alongside
      conventional karyotyping. DATA COLLECTION AND ANALYSIS: Nine papers were included
      in the systematic review and meta-analysis. All statistical analyses were
      performed using stata 11.0 (Stata Corp., College Station, TX, USA). MAIN RESULTS:
      There was agreement between CMA and karyotyping in 86.0% of cases (95% CI 77.0
      96.0%). CMA detected 13% (95% CI 8.0-21.0) additional chromosome abnormalities
      over conventional full karyotyping. In addition, traditional, full karyotyping
      detected 3% (95% CI 1.0-10.0%) additional abnormalities over CMA. The incidence
      of a variant of unknown significance (VOUS) being detected was 2% (95% CI 1.0
      10.0%). AUTHOR'S CONCLUSIONS: Compared with karyotyping, there appears to be an
      increased detection rate of chromosomal abnormalities when CMA is used to analyse
      the products of conception; however, some of these abnormalities are VOUS, and
      this information should be provided when counselling women following miscarriage
      and when taking consent for the analysis of miscarriage products by CMA.

PMID- 23859083
TI  - Oxidation of manganese(II) during chlorination: role of bromide.
AB  - The oxidation of dissolved manganese(II) (Mn(II)) during chlorination is a
      relatively slow process which may lead to residual Mn(II) in treated drinking
      waters. Chemical Mn(II) oxidation is autocatalytic and consists of a homogeneous
      and a heterogeneous process; the oxidation of Mn(II) is mainly driven by the
      latter process. This study demonstrates that Mn(II) oxidation during chlorination
      is enhanced in bromide-containing waters by the formation of reactive bromine
      species (e.g., HOBr, BrCl, Br2O) from the oxidation of bromide by chlorine.
      During oxidation of Mn(II) by chlorine in bromide-containing waters, bromide is
      recycled and acts as a catalyst. For a chlorine dose of 1 mg/L and a bromide
      level as low as 10 MUg/L, the oxidation of Mn(II) by reactive bromine species
      becomes the main pathway. It was demonstrated that the kinetics of the reaction
      are dominated by the adsorbed Mn(OH)2 species for both chlorine and bromine at
      circumneutral pH. Reactive bromine species such as Br2O and BrCl significantly
      influence the rate of manganese oxidation and may even outweigh the reactivity of
      HOBr. Reaction orders in [HOBr]tot were found to be 1.33 (+/-0.15) at pH 7.8 and
      increased to 1.97 (+/-0.17) at pH 8.2 consistent with an important contribution
      of Br2O which is second order in [HOBr]tot. These findings highlight the need to
      take bromide, and the subsequent reactive bromine species formed upon
      chlorination, into account to assess Mn(II) removal during water treatment with
      chlorine. 

PMID- 23859084
TI  - Effect of dietary mannanase-hydrolysed copra meal on growth performance and
      intestinal histology in broiler chickens.
AB  - We investigated mannanase-hydrolysed copra meal (MCM), which contains beta-1,4
      mannobiose (MNB), for its capacity to improve growth performance and activate
      intestinal villus function. Seven-day-old chicks were separated into four flocks
      with an equal mean body weight and then fed a basal diet (control) or a diet
      supplemented with 0.02% or 0.1% MCM. After 7 weeks, the feed intake and body
      weight were determined and then used to calculate the feed efficiency (FE).
      Moreover, the intestinal segments were examined by light microscopy and scanning
      electron microscopy (SEM) for cellular and morphological changes in the villus.
      Although feed intake was not significantly different among the experimental
      groups, the body weight gain and FE were significantly higher in the 0.1% MCM
      group than in the control group (p < 0.05), while feed intake tended to be higher
      in the 0.02% and 0.1% MCM groups. The cellular area of the ileum was
      significantly higher in the 0.02% and 0.1% groups in relation to that in the
      control group (p < 0.05). Furthermore, the cellular area of the duodenum and the
      jejunum tended to be higher in the 0.02% and 0.1% MCM groups. For the correlation
      analysis, a significant correlation was observed between the dosage of MCM and
      the cell area of the duodenum, jejunum and ileum. Moreover, the number of mitotic
      cells was higher in the 0.1% MCM group. As shown by SEM, the cells at the villi
      tips were protuberant in appearance in the 0.02% and 0.1% MCM treatments when
      compared with the relatively flat cells of the control. On the duodenal villus
      surface of the 0.1% MCM group, some cells devoid of microvilli were observed,
      suggesting that the increased protuberance of these cells represents increased
      absorption activity. Although intestinal villus height and area did not
      significantly differ among groups, the levels of these parameters tended to
      increase in the experimental groups relative to the control. The present
      morphological findings reveal that MNB might be effective for activating
      intestinal absorptive function, and that the functional activation promotes the
      growth of the chickens. 

PMID- 23859085
TI  - Robot-assisted anatrophic nephrolithotomy with renal hypothermia for managing
      staghorn calculi.
AB  - Treatment of patients with staghorn calculi with percutaneous nephrolithotomy can
      be challenging, often necessitating multiple tracts or sessions for complete
      stone clearance. Although open anatrophic nephrolithotomy can result in higher
      stone-free rates, it is rarely performed because of increased morbidity. To
      provide a minimally invasive alternative, we developed the technique of robot
      assisted anatrophic nephrolithotomy (RANL) incorporating ice slush for renal
      hypothermia. Three patients with staghorn calculi (mean total stone volume
      12887.67 mm(3)) underwent RANL with iced cold ischemia. A GelPOINTTM port was
      used for ice slush insertion. Intracorporeal temperatures were <9 degrees C
      within 30 minutes of cold ischemia. Mean console and cold ischemia times were 167
      and 56.7 minutes, respectively. Mean blood loss was 100 mL. There were no
      complications. Two patients had residual fragments measuring 13 mm, and two 9 mm
      stones, respectively. RANL with iced cold ischemia is a safe and feasible option
      that may be considered in patients with staghorn stones. Further study is needed
      to refine the technique and assess long-term functional outcomes.

PMID- 23859087
TI  - Advancing education in psychiatry.

PMID- 23859086
TI  - Clinical response of edentulous people treated with mini dental implants in nine
      dental practices.
AB  - OBJECTIVES: To analyse implant survival, prosthetic aftercare and quality of life
      (QoL) after stabilisation of complete dentures with mini-implants. BACKGROUND:
      Many edentulous patients refuse implant therapy due to the expenses and fear of
      surgery. Studies on minimally invasive and low-cost mini-implants remain rare.
      MATERIALS AND METHODS: A total of 133 participating patients from nine private
      practices were evaluated via patient records, questionnaires and clinical
      examinations. Complications, maintenance, QoL questions and the German short
      version of the oral health impact profile (OHIP-G14) were analysed. RESULTS:
      After 7 to 61 months, 15 of 336 maxillary implants and 11 of 402 mandibular
      implants had to be removed. In addition, four mandibular implants experienced
      fracture. The difference between the 4-year survival rates of 94.3% for the
      maxilla and 95.7% for the mandible was not statistically significant (p = 0.581).
      All original 144 overdentures remained functional. The prosthetic interventions
      were typically limited to repairs of acrylic base fractures (about one in five
      patients), changes of plastic O-rings and relining procedures. The participants
      showed OHIP-G14 scores (median = 2) that were comparable with those of patients
      with overdentures retained by conventional implants. CONCLUSIONS: Mini-implant
      survival was similar to that of regular-diameter implants. Although some
      prosthetic aftercare was necessary, none of the overdentures had to be replaced.
      Prospective studies comparing conventional and mini-implants are warranted.

PMID- 23859088
TI  - The state of psychotherapy supervision: recommendations for future training.
AB  - This paper reviews the current state of psychotherapy supervision in psychiatric
      training programmes. A focused literature search was carried out that examined
      three questions concerning the content, process and outcome of psychotherapy
      supervision. Results indicate that although requirements for training have
      broadened somewhat, methods of instruction in supervision have remained the same
      for many decades. In addition, there is a lack of discussion on what supervision
      outcomes should be assessed. This paper explores these areas and provides some
      suggestions for the future of psychotherapy supervision that are evidence-based
      and generalizable to an international audience. It is time to arrive at an
      international consensus about guidelines for psychotherapy supervision in
      psychiatry training programmes. This paper attempts to provide a starting place
      for psychotherapy supervisors and educators so that we can advance the field
      forward.

PMID- 23859089
TI  - Educating psychiatry residents in neuropsychiatry and neuroscience.
AB  - Neuropsychiatry and psychiatric neuroscience should be part of the general
      psychiatry curriculum so that graduate psychiatrists will be able to allow their
      patients the benefit of neuroscientifically informed diagnosis and treatment.
      Current neurology and neuroscience educational requirements for US psychiatry
      training are reviewed. The draft milestone requirements for clinical neuroscience
      training as part of the US Accreditation Council for Graduate Medical Education's
      Next Accreditation System are also provided. Suggestions for the neuropsychiatric
      and neuroscience content of psychiatry residency training are made, along with a
      description of pedagogic methods and resources. Survey data are reviewed
      indicating agreement by programme directors with the importance of neuroscience
      training and an increase in the amount of time devoted to this area. Faculty
      staff development in neuropsychiatry and neuroscience literacy will be needed to
      provide high quality training in these areas.

PMID- 23859090
TI  - Journal club for faculty or residents: a model for lifelong learning and
      maintenance of certification.
AB  - The journal club offers a model for lifelong learning and maintenance of
      certification (MOC) for residents and faculty staff. First, it sharpens
      participants' critical appraisal skills by providing a space to discuss relevant
      medical literature. Second, it motivates participants to seek new medical
      literature on their own using technology. Our model sets forth a four-year
      journal club curriculum that could be used as one continuous curriculum or in
      bits and pieces. In the first year, the focus is teaching residents how to read
      an article. The second year focuses on what is of interests to the reader. The
      third year applies the resident's appraisal skills to assigned articles to test
      whether they can determine which have reliable and valid findings and which are
      flawed. In the fourth year residents are asked to distinguish whether articles
      are well researched and referenced. Our model also motivates participants to read
      articles in faculty journal clubs throughout their career. In most academic
      settings category 1 continuing medical education (CME) credits can be awarded so
      journal club can have the added benefit of satisfying maintenance of
      certification CME credits. From journal club both residents and faculty can learn
      what is new and learn to apply this new information in their practice. Finally,
      because technology creates an overabundance of relevant medical literature,
      participants using our model can develop strong critical appraisal skills and
      methods for organizing the information they find that make this information
      readily available for future use and retrieval.

PMID- 23859091
TI  - Stepping stones for psychiatry residents who pursue scientific research careers.
AB  - Advances in areas of neuroscience are highly relevant to psychiatric disorders
      but there exists a gap between discoveries in neuroscience and the practice of
      clinical psychiatry. Psychiatry is a field in need of high impact research
      conducted by physician-scientists who have first-hand experience treating
      patients with mental illness and who use this clinical knowledge to improve and
      discover better or novel interventions. This paper focuses primarily on the
      training of psychiatry residents for successful scientific research careers and
      what residency programmes and others can do to help them succeed. Changes also
      need to be made at a regulatory level to enhance the research training and
      literacy of psychiatry residents. The shortage of psychiatrists who are well
      trained in basic and translational research can only be remedied if the path to
      becoming an independent investigator is lined with stepping stones that support
      success, including during the residency years. Partnerships among funding
      agencies, professional societies and training institutions can lay the groundwork
      for our psychiatric trainees to stay on the path to rewarding scientific research
      careers.

PMID- 23859092
TI  - Assessing competencies during education in psychiatry.
AB  - The utilization of competencies in medical education is relatively recent. In
      1999 the United States Accreditation Council for Graduate Medical Education
      (ACGME) established six main competencies. Since then, the American Board of
      Psychiatry and Neurology have approved a specific list of competencies for their
      specialities in each of the ACGME's core competency areas. Assessment of
      competencies in both medical students and residents can be achieved through such
      methods as structured case discussion, direct observation, simulation,
      standardized patients, and 360-degree assessments, etc. Each assessment
      methodology has specific applications in the discipline of psychiatry. This paper
      reviews the different methods for assessing competencies with specific examples
      in psychiatric education. It is not intended as a comprehensive review of all
      assessment methods, but to provide examples and strategies to guide psychiatric
      educators in their practice. Students and residents were intentionally separated
      because there are differences in the teaching goals and objectives, and thus in
      the assessment purposes and design. Students are general, undifferentiated
      physicians-in-training who need to learn about psychiatric nosology,
      examinations, and treatment. Residents are mental health professionals who need
      more in-depth supervision in order to hone skills in all the specialized areas
      that arise in psychiatric practices, making supervision a vital part of residency
      programs.

PMID- 23859093
TI  - Methodologies and study designs relevant to medical education research.
AB  - Research is an important part of educational scholarship. Knowledge of research
      methodologies is essential for both conducting research as well as determining
      the soundness of the findings from published studies. Our goals for this paper
      therefore are to inform medical education researchers of the range and key
      components of educational research designs. We will discuss both qualitative and
      quantitative approaches to educational research. Qualitative methods will be
      presented according to traditions that have a distinguished history in particular
      disciplines. Quantitative methods will be presented according to an evidence
      based hierarchy akin to that of evidence-based medicine with the stronger designs
      (systematic reviews and well conducted educational randomized controlled trials)
      at the top, and weaker designs (descriptive studies without comparison groups, or
      single case studies) at the bottom. It should be appreciated, however, that the
      research question determines the study design. Therefore, the onus is on the
      researcher to choose a design that is appropriate to answering the question. We
      conclude with an overview of how educational researchers should describe the
      study design and methods in order to provide transparency and clarity.

PMID- 23859094
TI  - Impact of changes in psychiatric practice on psychiatric education in the USA.
AB  - The evidence base for the field of psychiatry is rapidly changing in the twenty
      first century due to advances in neuroscience that are in the process of being
      translated into clinical interventions. The delivery systems for mental
      healthcare are simultaneously undergoing dramatic transformations as the field
      attempts to meet population needs effectively and efficiently. These changes
      demand a reconsideration of the content and priorities of psychiatric training
      programmes for both medical students and residents. This article examines the
      current state of psychiatric practice, as well as future challenges and potential
      models of practice, and discusses how these changes are impacting the present
      needs of trainees. Preparing today's medical students and residents to be active
      participants in the creation of the mental healthcare delivery system of the
      future is the key to the success of the specialism and to the welfare of
      tomorrow's patients.

PMID- 23859095
TI  - What makes a difference to patients?
AB  - To make a difference to patients who increasingly suffer multiple chronic
      conditions, in a healthcare system that is capable of providing excellent care
      but is often ineffective and at cross-purposes in its application, means being
      prepared to take a different approach not only to the delivery of patient care,
      but to the education of physicians and other healthcare professionals. The model
      we must now practice and teach is one that emphasizes collaboration and
      prevention, quality and efficiency. Changes in practice recommended by the 2001
      US Institute of Medicine report are being implemented system-wide, following the
      enactment of the US Patient Protection and Affordable Care Act. This paper
      discusses the evolving needs of patients with chronic psychiatric illness, and
      the psychiatrist's role in a rapidly changing healthcare landscape as a care
      provider, an interdisciplinary role model, and educator. In an aging population
      in which multi-morbidity is the norm, episodic, crisis-driven care is
      prohibitively expensive and does not serve patients well. Yet we still teach that
      model of care. The medications we prescribe for psychiatric illness, particularly
      antipsychotics, can cause and/or aggravate some of the commonest chronic medical
      illnesses; psychiatric educators must address the management of these
      complications. The management of chronic psychiatric illness in multi-morbid
      patients demands that we practice and teach a 'whole patient' approach to care,
      preferably delivered as part of a patient-centred team. The Affordable Care Act
      has mandated and created opportunities for new models designed to facilitate
      this, and a paradigm shift is needed in medical education. Clinicians must become
      adept at identifying underlying and contributing factors and collaborating with
      the patient, other providers, and the patient's family and significant others.
      Psychiatric formulation and patient care rely on these principles; we must now
      teach their application to other specialties, disciplines and professions.

PMID- 23859096
TI  - Lessons from psychiatry and psychiatric education for medical learners and
      teachers.
AB  - Medical learners, teachers, and institutions face significant challenges in
      health care delivery and in training the next generation of clinicians. We
      propose that psychiatry offers lessons which may help improve how we take care of
      patients and how we teach others to care for patients. Our objective is to
      discuss what learners and teachers can learn from psychiatry, organized around
      (1) how we make decisions, (2) how we learn, and (3) how we reflect on our
      practice. Information from clinical care, education, neuroscience and other
      aspects of life (e.g. business, creativity, and research) help us on these
      processes. We make 'good' decisions in concert with patients and learners, by
      listening to their experiences, asking questions and exploring subjective and
      objective information. Our learning has a neurobiological basis, and is
      effectively furthered by personalization, reinforcement, acquisition of critical
      thinking skills, and assessment of our limitations and errors. Our ability to
      reflect is determined by attitude, skill, tolerating ambiguity or dissonance, and
      planning for the unexpected. These processes - in addition to knowledge and other
      skills - will help physicians be successful in practice, learning and teaching,
      research and leadership.

PMID- 23859097
TI  - New directions in medical education related to psychiatry.
AB  - The 100-year anniversary of the Flexner report provides an opportunity to reflect
      on the future of medical education. We will consider the legacy of the original
      report, the centenary follow up to that report and consider how these, in concert
      with emerging learning theories, will influence medical education. We first
      provide a brief overview of the original Flexner report and review the
      recommendations of the 2010 centenary follow up to the report. We then discuss
      some of the major developments in learning theory and consider how they have
      influenced medical education. In general, there has been a gradual shift from
      passive to active methods, spurred in part by constructivist theories of
      learning. Many of the attitudes and skills required are particular strengths of
      the psychiatrist, making psychiatric educators particularly suitable to lead
      curricular change. Although much literature is devoted to determining the 'best'
      educational method, we take an ecumenical approach, suggesting that the various
      pedagogical approaches are all legitimate educational tools from which to choose.
      Each has its strength and limitations, and when designing a curriculum we should
      consider these when making pedagogical choices. We finish with some practical
      advice for those contemplating curricular change.

PMID- 23859098
TI  - As technology and generations in medical education change, what remains is the
      intersection between educator, learners, assessment and context.
AB  - The information era has begun to create major shifts in educational systems,
      including those in undergraduate medical and graduate psychiatric training
      programmes. Despite these changes, teaching and learning in formal educational
      settings remains predominately the product of the intersection between educator,
      learners, assessment and context. This article reviews intrinsic and external
      forces influencing each of these elements, such as intergenerational differences
      in teaching and learning styles, education technologies as they relate to
      delivery and maintenance of curricula, competency frameworks of assessment, and
      individual learning and teaching development plans. Maintaining a focus on the
      relationship between these factors and re-conceptualizing psychiatric education
      and formal medical education systems in general as a mutual two-way learning
      exchange between participants will promote careers of lifelong learning.

PMID- 23859099
TI  - Personal reflections on a life of learning and teaching psychiatry.
AB  - I have been actively learning and teaching psychiatry since starting residency in
      1966. Over the decades my educational endeavours have been guided by a fairly
      consistent set of operating principles. Fortunate opportunities in several
      excellent psychiatry departments and national organizations have allowed me to
      experiment, and these principles have tested well. My objectives for this article
      are to review these principles and describe some educational activities that have
      provided notable pleasure and lasting satisfaction. Readers may wish to try out
      some of these ideas. They have worked for me, and they may work for others as
      well.

PMID- 23859100
TI  - Iridium and ruthenium catalyzed syntheses, hydroborations, and metathesis
      reactions of alkenyl-decaboranes.
AB  - The selective syntheses of new classes of 6,9-dialkenyl- and 6-alkenyl
      decaboranes and 6-alkyl-9-alkenyl-decaboranes have been achieved via iridium and
      ruthenium catalyzed decaborane and 6-alkyl-decaborane alkyne-hydroborations.
      Reactions employing [Cp*IrCl2]2 and [RuCl2(p-cymene)]2 precatalysts gave beta-E
      alkenyl-decaboranes, while the corresponding reactions with [RuI2(p-cymene)]2
      gave the alpha-alkenyl-decaborane isomers, with the differences in product
      selectivity suggesting quite different mechanistic steps for the catalysts. The
      alkenyl-decaboranes were easily converted to other useful derivatives, including
      coupled-cage and functionally substituted compounds, via iridium-catalyzed
      hydroborations and ruthenium-catalyzed homo and cross olefin-metathesis
      reactions. 

PMID- 23859101
TI  - Non-HDL cholesterol vs. apo B for risk of coronary heart disease in healthy
      individuals: the EPIC-Norfolk prospective population study.
AB  - BACKGROUND: There is an ongoing debate about the performance of non-high-density
      lipoprotein cholesterol (non-HDL-C) compared with apolipoprotein B (apo B) in the
      prediction of coronary heart disease (CHD) risk. Therefore, we compared the
      associations between non-HDL-C and apo B in regard to CHD among apparently
      healthy Western European individuals. DESIGN: In the European Prospective
      Investigation into Cancer and Nutrition (EPIC)-Norfolk prospective population
      study, 25,639 men and women aged 45-79 years were followed for 11.4 +/- 2.8
      years. Those with diabetes or prevalent CHD at baseline were excluded. A total of
      2066 (12.1%) participants developed CHD during 195 692 person-years follow-up.
      RESULTS: The multivariable-adjusted hazard ratio [HR] of future CHD per one
      standard deviation increase was 1.22 [95% confidence interval (CI): 1.17-1.27]
      for LDL-C, 1.26 (95% CI 1.20-1.31) for non-HDL-C and 1.19 (95% CI 1.14-1.24) for
      apo B, respectively. The multivariable-adjusted HR of future CHD in the highest
      quartile LDL-C was 1.67 (95% CI: 1.47-1.91). For non-HDL-C and apo B, these
      respective HRs were 1.87 (95% CI: 1.62-2.15) and 1.56 (95% CI: 1.36-1.78). Kaplan
      Meier survival analyses showed that there was incremental and comparable increase
      in risk of CHD with increasing quartiles of both non-HDL-C and apo B.
      CONCLUSIONS: In this prospective study, non-HDL-C and apo B were comparable in
      their ability to predict risk of future CHD.

PMID- 23859102
TI  - Cytokines and tumor markers in potentially malignant disorders and oral squamous
      cell carcinoma: a pilot study.
AB  - OBJECTIVE: To evaluate serum levels of interleukin (IL)-1, IL-6, IL-8, IL-10,
      soluble IL-2 receptor (sIL-2R), squamous cell carcinoma antigen (SCCA), tissue
      polypeptide-specific antigen (TPS) and vascular endothelial growth factor (VEGF)
      in patients with potentially malignant disorders (PMD), oral squamous cell
      carcinoma (OSCC), or status-post (SP) OSCC. SUBJECTS AND METHODS: Blood was
      collected from 47 patients, either controls or diagnosed with PMD, OSCC, or
      SPOSCC. Levels of cytokines and tumor marker were evaluated by ELISAs. Normal
      levels were based on previous studies and pathology determined by chi-square and
      Fisher's exact tests. P <= 0.05 was considered statistically significant.
      RESULTS: Above normal levels of SCCA were found for OSCC and dysplasia patients
      (33.3% and 11.1%, respectively) and high range of normal (upper 20% of the normal
      range) for lichen planus, SPOSCC, and dysplasia patients (6.67%, 33.3%, and
      22.2%, respectively), differences that approached statistical significance (P =
      0.055). No differences were found between groups for other tested markers. A
      progression was seen for SCCA from high range of normal in SPOSCC to a mixture of
      high normal and elevated in dysplasia to elevated in active OSCC, suggesting that
      SCCA may be correlated with cancer progression. CONCLUSION: Higher levels of
      serum SCCA may serve as a marker for dysplasia and progression to oral
      carcinogenesis.

PMID- 23859103
TI  - Identification of a common binding mode for imaging agents to amyloid fibrils
      from molecular dynamics simulations.
AB  - Amyloid diseases are characterized by the misfolding and deposition of proteins
      in the body in the form of insoluble amyloid fibrils. Alzheimer's disease and
      type 2 diabetes mellitus are two examples of amyloid diseases which are closely
      related both with respect to the atomic structures of the amyloid fibrils and the
      disease pathology. Alzheimer's disease is very difficult to diagnose, and much
      research is being performed to develop noninvasive diagnostic methods, such as
      imaging with small-molecule agents. The interactions between amyloid fibrils and
      imaging agents are challenging to examine experimentally due to the insoluble
      nature of amyloid fibrils. This study uses molecular dynamics simulations to
      investigate the interactions between 13 aromatic amyloid imaging agents,
      entailing 4 different organic scaffolds, and a model of an amyloid fibril.
      Clustering analysis combined with free energy calculations are used to categorize
      and rank the resulting complexes. Several binding modes are identified across the
      different ligand scaffolds, however a common favorable binding mode can be
      identified in which the agent is placed in surface grooves along the amyloid
      fibril axis. The existence of multiple binding modes for imaging agents is
      proposed to originate from subtle differences in amino acid composition of the
      surface grooves on an amyloid fibril, resulting in fine tuning of the binding
      affinities for a specific amyloid fibril. 

PMID- 23859104
TI  - [The mediocre results of dieting].
AB  - Diets involving a reduction in caloric intake are frequently prescribed for the
      treatment of obesity, but their long-term efficacy is questionable. We considered
      a calorie restricted diet successful if the weight loss was >= 5% after at least
      3 years follow up. From published data, calculating a definitive percentage of
      successful cases is difficult because of the way data are presented and because
      loss to follow-up is not corrected for in many studies. Judging by the best data
      available, the success rate is very low. Most individuals will regain weight and
      sometimes even more than they lost in the first place. The mechanisms driving
      this weight increase are a decrease in energy expenditure and an increased
      appetite which is mediated by factors such as leptin. If the first attempt to
      lose weight fails, the advice to go on a diet should not be endlessly repeated;
      stabilizing the individual's weight would probably be a more realistic goal.

PMID- 23859105
TI  - [Guideline 'Wound Care': recommendations for 5 challenging areas].
AB  - The interdisciplinary evidence-based guideline 'Wound Care' covers the treatment
      and management of acute wounds in adults and children and by all wound care
      disciplines. This guideline answers 5 basic questions with 38 recommendations
      covering wound cleansing, pain relief, instructing the patient, various dressings
      and the organisational aspects of wound care. The guideline recommendations
      include not to cleanse wounds that are primarily closed, to cleanse acute open
      wounds with clean tap water, to use the WHO pain ladder as the basis for the
      choice of analgesics for continuous wound pain, to administer lidocaine or
      prilocaine for localized pain relief during manipulation, not to cover primarily
      closed wounds with dressings, to use simple dressings for open wounds and to give
      the patient clear instructions. The guideline also advises about wound
      registration, documentation and hand-over of wound care, and recommends making
      clear agreements about referrals and responsibilities.

PMID- 23859106
TI  - [Symptomatic hypocalcaemia on denosumab use].
AB  - BACKGROUND: Bone resorption inhibitors such as denosumab may induce symptomatic
      hypocalcaemia if a vitamin D deficiency is present. Amongst other causes, this
      type of deficiency may arise following bariatric surgery. CASE DESCRIPTION: We
      describe a 51-year-old woman who, a few years after undergoing bariatric surgery,
      developed symptomatic hypocalcaemia after she started taking denosumab.
      CONCLUSION: An adequate calcium and vitamin D status is a general condition
      before prescribing medication to treat osteoporosis. Therefore we recommend that
      before starting treatment with a bone resorption inhibitor that not only the
      calcium but also the vitamin D status should be determined, and if necessary,
      optimised.

PMID- 23859107
TI  - [Propensity scores in observational research].
AB  - A propensity score is the probability of being treated or exposed, given measured
      confounders such as age. Propensity score methods can control for measured
      confounders in observational research, but not for unmeasured confounders. Study
      participants with the same propensity score will, on average, have a similar
      distribution of measured confounders. The propensity score can be used to control
      for confounding by means of stratification, matching, including the propensity
      score as a covariate in a multivariable regression model, or by weighting the
      study population using the propensity score. Propensity score methods can often
      control for more confounders than other methods, particularly in the case of a
      rare outcome. Reports on propensity score methods should mention which
      confounders were included in the propensity score and to what extent confounders
      were balanced across study groups, after stratification based on the propensity
      score.

PMID- 23859108
TI  - [Carbon monoxide poisoning after smoking from a water pipe].
AB  - BACKGROUND: Smoking from a water pipe has become increasingly popular, but this
      is not as innocent as it seems. CASE DESCRIPTION: Three women presented to the
      emergency department after having smoked from a water pipe. The first patient had
      experienced a syncopal episode and still had symptoms of dizziness and a headache
      afterwards. The second patient only had a headache and the third had no symptoms.
      The physical examinations and standard vital sign measurements of all three
      patients were normal. Analyses of the arterial blood gases, however, showed
      carbon monoxide (CO) poisoning: the patients had HbCO concentrations of 22, 19.5
      and 5.7%, respectively. We administered high concentrations of oxygen to each,
      but the first 2 patients continued to experience symptoms for several weeks. The
      CO poisoning was probably caused by the incomplete combustion of the charcoal in
      the water pipe which resulted in CO being released. CONCLUSION: The regular or
      even one-time use of a water pipe containing tobacco or an aromatised substance
      can cause CO poisoning. Patients can continue to experience symptoms for weeks
      after an episode of acute CO poisoning.

PMID- 23859109
TI  - [Methaemoglobinaemia after using EMLA cream].
AB  - BACKGROUND: The use of creams is considered to be generally safe. However,
      systemic side effects can occur. CASE DESCRIPTION: A 22-year-old woman came to
      the emergency department with dyspnea, confusion and 'blue' skin after laser
      treatment of the upper legs for excessive hair. She had used three tubes of a
      eutectic mixture of local anaesthetics (EMLA) cream containing
      lidocaine/prilocaine for analgesia. Her oxygen saturation was 87%, measured with
      pulse oximetry. Blood gas analysis showed a concentration of oxy-Hb of 79% and a
      met-Hb of 19%. Our working diagnosis was methaemoglobinaemia as a result of using
      excessive amounts of EMLA cream. Because the met-Hb concentration decreased
      spontaneously and the oxy-Hb concentration consequently normalised, we did not
      administer methylene blue. The patient was discharged symptom-free after several
      hours of observation. CONCLUSION: An overdose of EMLA cream, whether or not in
      combination with laser-induced skin damage, can produce a high systemic o
      toluidine concentration. This can lead to methaemoglobinaemia. In such cases, the
      pulse oximeter is not reliable for measuring the oxygen saturation; therefore,
      blood gas analysis is necessary for making a diagnosis.

PMID- 23859110
TI  - [Acute liver injury in a patient with anorexia nervosa].
AB  - BACKGROUND: Anorexia nervosa is associated with somatic complications. Mildly
      abnormal liver tests are frequently seen; however, severe acute liver injury is
      rare in anorexia. CASE DESCRIPTION: A 23-year-old woman was admitted with acutely
      elevated liver enzymes and hypoglycemia. All diagnostic tests for acute hepatitis
      were negative. Therefore, we made the diagnosis of 'acute liver injury due to
      anorexia'. With supportive care such as rehydration, drip-feed and infusions with
      glucose, the patient recovered and her liver tests improved. CONCLUSION: Severe
      acute liver injury is a rare but life-threatening complication of anorexia
      nervosa. Its aetiology is unknown. Autophagy of hepatocytes, hypoperfusion of the
      liver and oxidative stress may play a role in the pathogenesis. Treatment
      consists of rehydration and nutritional support.

PMID- 23859111
TI  - [A woman with a growing skull].
AB  - In a 79-year-old female, a markedly elevated alkaline phosphatase level was found
      by chance. She had noticed her hats had become too small. Clinical examination
      revealed a large skull with frontal bossing. Bone scintigraphy showed increased
      activity of bone metabolism in the skull. These three findings combined are
      considered a classic example of Paget's disease. 

PMID- 23859112
TI  - [Ductoscopy for pathologic nipple discharge].
AB  - Pathologic nipple discharge is a symptom that frequently causes female patients
      to visit the outpatient breast clinic. In the vast majority of cases, the symptom
      is caused by a benign intraductal laesion. The options for diagnosis and
      treatment have long been limited; surgery was not infrequently the treatment of
      choice. With the advent of breast ductoscopy, a micro-endoscopic procedure, it is
      possible to visualise abnormalities in the ductal system. Tissue for
      histopathological investigation can be retrieved from the duct and the condition
      can be treated. The patient with nipple discharge is consequently prevented from
      having to undergo an invasive and fairly 'blindly' executed procedure under
      general anaesthesia. The miniscule dimensions of the duct in which the technique
      is carried out pose the greatest challenge to the further development of the
      ductoscope. 

PMID- 23859113
TI  - [The Health Council of the Netherlands' advice 'A closer look at Lyme disease'].
AB  - When diagnosed at an early stage, Lyme disease responds well to treatment with
      antibiotics. However, the picture becomes more complex in patients whose symptoms
      are not particularly clear, in patients with later stage disease and in patients
      who experience persistent symptoms whose cause cannot clearly be linked to Lyme
      disease. Diagnosis and treatment of the condition are debated, not only between
      patients and physicians but also among professional groups. The Health Council of
      the Netherlands drew up the advisory report 'A closer look at Lyme disease' at
      the request of the Lower House of the Dutch Parliament. The immediate reason for
      this request was a citizens' initiative by the Dutch Association for Lyme
      Patients. The Council formulated its recommendations with a view to helping
      physicians and patients to reach common viewpoints. It enlisted a broad-based
      committee of experts to harness the best available knowledge and use the
      experience of all those involved. 

PMID- 23859114
TI  - [The Health Council of the Netherlands' advice on Lyme disease].
AB  - There are many misconceptions about Lyme disease. At the initiative of the Dutch
      Association for Lyme Patients, the Lower House of the Dutch Parliament requested
      a report on Lyme disease. The Health Council of the Netherlands advised
      standardization of Lyme serology in all Dutch laboratories as soon as possible.
      Standardization of diagnostic serological tests was strongly recommended. Studies
      into new tests which discriminate between active disease and past infection were
      recommended. Patients with Lyme disease were divided in those with Lyme specific
      and non-specific symptoms and duration of symptoms. Treatment advice was given
      for each of these 6 patient categories with a prominent role for the decision of
      the attending physician. Additionally it was advised to set up specialized
      treatment centers with a multidisciplinary approach. The report clearly shows the
      problems in care for Lyme patients from the perspective of both patients and
      physicians, but is cautious in the solutions offered. 

PMID- 23859115
TI  - Cetuximab/irinotecan-chemotherapy in KRAS wild-type pretreated metastatic
      colorectal cancer: a pooled analysis and review of literature.
AB  - INTRODUCTION: Cetuximab and irinotecan are effective agents in advanced
      colorectal cancer (CRC) after either irinotecanor oxaliplatin-based first-line
      chemotherapy. Here, the efficacy of this combination in patients with the KRAS
      wild-type gene as second- or further-line therapy is reviewed and data are
      collected in a pooled analysis. METHODS: Studies that enrolled pretreated CRC
      patients for second-line therapy or beyond were identified using electronic
      databases (PubMed and EMBASE). A systematic analysis was conducted using
      Comprehensive Meta Analysis (version 2.2.064) to calculate the event rate of
      response and the 95% confidence interval. The weighted median overall survival
      (OS) and progression-free survival (PFS) were also calculated with NCSS 2007
      software. We tested for significant heterogeneity using Cochran's chi-square test
      and the I(2) index. RESULTS: Twenty-five studies published between 2007 and 2012
      were eligible for this analysis, with a total of 1,712 KRAS wild-type patients
      enrolled. The overall response rate was 31.9% with similar response rates of 28.
      7% for second-line treatment and 31.1% for third or further lines. The overall
      weighted median OS and PFS were 12.5 and 6 months with a weighted OS of 11.56 and
      12.2 months for second- and further-line CRC settings, respectively. CONCLUSION:
      In metastatic KRAS wild-type CRC patients pretreated with one or more lines of
      therapy, cetuximab plus irinotecan-based chemotherapy is an active treatment.
      Response rates and survival outcomes appear similar in second-line therapy or
      beyond.

PMID- 23859116
TI  - Development of analytical method for determination of 1,4-dioxane in cleansing
      products.
AB  - OBJECTIVE: 1,4-Dioxane is a toxic by-product formed during the synthesis of
      surfactants used in finished cosmetic products. There are no set permissible
      levels of toxic impurities in finished cosmetic products in Japan. In this study,
      we have established a simple and sufficiently precise analytical method to
      determine the activity of 1,4-dioxane in finished cosmetic cleansing products.
      METHODS: This method involves the standard addition approach and headspace-gas
      chromatography/mass spectrometry without pre-conditioning. RESULTS: Fifteen
      cleansing products that are sold in the Japanese market, such as shampoo, hand
      soap, and dishwashing liquid, were analyzed, and 1,4-dioxane was detected at a
      concentration of a few micrograms per gram of the product in almost all of them.
      The concentration of 1,4-dioxane in two dishwashing liquid products was high. The
      maximum concentration of 1,4-dioxane in all of the cleansing products was below
      10 MUg g(-1) , which is a limit that is thought to be safe and technically
      achievable through the application of good manufacturing practices. Since 1,4
      dioxane is formed during the synthesis of polyoxyethylene ether sulfate, it was
      detected at high concentrations in cleansing products that contained a lot of
      polyoxyethylene ether sulfate. CONCLUSION: Control of the synthesis of
      polyoxyethylene ether sulfate can be effective in reducing the concentration of
      1,4-dioxane in cleansing products.

PMID- 23859117
TI  - Venturi-electrosonic spray ionization cataluminescence sensor array for
      saccharides detection.
AB  - In this article, a Venturi electrosonic spray ionization (V-ESSI)
      cataluminescence (CTL) sensor array was reported for discriminating saccharides
      in solution. Integrating electrosonic spray ionization (ESSI), a liquid system of
      Venturi self-pumping injection for the CTL reaction, was fabricated for enhancing
      CTL reactivity of aqueous samples. Comparing with simple Venturi injection by air
      and Venturi easy ambient sonic-spray ionization without electric assistance (V
      EASI), the remarkable enhancement of CTL signals resulted from V-ESSI. This
      system showed higher cross-reactive CTL responses catalyzed by alkaline earth
      metal-nanomaterials than other catalysts, giving different signals for a given
      saccharide on different catalysts and different responses for different
      saccharides on the same catalyst. Then, a 4 * 2 CTL sensor array was used for
      obtaining "fingerprints" of distinct CTL response patterns. Analyzed by linear
      discriminant analysis (LDA), this V-ESSI CTL sensor array not only achieved the
      well discrimination of different saccharides (99.9% of total variation) but also
      discriminated four groups of urine sugar-level for urine samples from diabetic
      patients (98.1% of discrimination accuracy). It had good reproducibility and gave
      a linear range of 22.5-67558 MUg/mL (R > 0.99) for xylose with a detection limit
      of 7.4 MUg/mL on MgO. As a new artificial tongue, this system provided a simple,
      rapid, low cost, low energy consumption, and environmentally friendly pathway for
      aqueous sample discrimination. It has dramatically expanded applications of the
      CTL-based senor array and will be applicable to clinical diagnoses, environment
      monitoring, industrial controls, food industry, and various marine monitoring. 

PMID- 23859118
TI  - Structure-based discovery of novel amide-containing nicotinamide
      phosphoribosyltransferase (nampt) inhibitors.
AB  - Crystal structures of several urea- and thiourea-derived compounds in complex
      with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to
      design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt
      BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal
      structure was subsequently obtained and enabled the design of additional amide
      containing inhibitors which incorporated various other fused 6,5-heterocyclic
      moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of
      these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors
      which also exhibited favorable in vitro ADME properties (microsomal and
      hepatocyte stability, MDCK permeability, plasma protein binding). An optimized
      compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM
      vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK
      properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a
      U251 mouse xenograft model. 

PMID- 23859119
TI  - Rear seat restraint system optimization for older children in frontal crashes.
AB  - OBJECTIVE: Analyses of crash injury data have shown that injury risk increases
      when children transition from belt-positioning boosters to the vehicle seat belt
      alone. The objective of this study is to investigate how to improve the restraint
      environment for these children. METHODS: A parametric analysis was conducted to
      investigate the effects of body size, seat belt anchorage locations, and rear
      seat design parameters on the injury risks in frontal crashes of children aged 6
      to 12 years old using a newly developed parametric child anthropomorphic test
      dummy (ATD) model. Restraint design optimizations were also conducted to obtain
      ranges of optimal restraint system configurations that provide best protections
      for 6-, 9-, and 12-year-old children. RESULTS: Simulation results showed that
      child body size was the dominant factor affecting outcome measures. In general,
      lower and more rearward D-rings (upper belt anchorages), higher and more forward
      lap belt anchorages, and shorter, stiffer, and thinner seat cushions were
      associated with improved restraint performance. In these simulations, children
      with smaller body sizes require more-forward D-rings, inboard anchors, and
      outboard anchor locations to avoid submarining. However, these anchorage
      locations increase head excursions relative to more-rearward anchorages.
      CONCLUSIONS: The balance of reducing head and knee excursions and preventing
      submarining indicates that an optimization approach is necessary to improve
      protection for 6- to 12-year-old child occupants. The findings of this study
      provided design guidelines for future rear seat restraint system.

PMID- 23859120
TI  - Nursing Activities Score as a predictor of family satisfaction in an adult
      intensive care unit in Greece.
AB  - AIM: To study family satisfaction with care in an Intensive Care Unit (ICU) and
      its association with nursing workload estimated by the Nursing Activities Score
      (NAS). BACKGROUND: Few previous studies have investigated the association between
      workload in ICUs and family satisfaction. METHODS: Family Satisfaction ICU 24 (FS
      ICU-24) questionnaires were distributed to 161 family members (106 respondents).
      Questionnaires' score, NAS measurements and Simplified Acute Physiology Score II
      (SAPS-II) data were analysed. RESULTS: The mean total level of family
      satisfaction was equal to 80.72% (+/- 9.59). Family members were more satisfied
      with the level of care compared with decision making. NAS values revealed a
      shortage of nurses in the morning shift. Moreover, there was a statistically
      significant positive correlation between NAS and total satisfaction after
      adjusting for age, length of stay and SAPS-II. CONCLUSIONS: Improvements in
      clinical practice require the measurement of care quality which particularly
      includes family satisfaction. Our results indicated that family members were less
      satisfied with decision making. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse
      managers should plan for the successful involvement of family members in the
      decision-making process. Higher levels of nurse staffing might improve the care
      provided.

PMID- 23859121
TI  - Observation of low energy Raman modes in twisted bilayer graphene.
AB  - Two new Raman modes below 100 cm(-1) are observed in twisted bilayer graphene
      grown by chemical vapor deposition. The two modes are observed in a small range
      of twisting angle at which the intensity of the G Raman peak is strongly
      enhanced, indicating that these low energy modes and the G Raman mode share the
      same resonance enhancement mechanism, as a function of twisting angle. The ~94
      cm(-1) mode (measured with a 532 nm laser excitation) is assigned to the
      fundamental layer breathing vibration (ZO' mode) mediated by the twisted bilayer
      graphene lattice, which lacks long-range translational symmetry. The dependence
      of this mode's frequency and line width on the rotational angle can be explained
      by the double resonance Raman process that is different from the previously
      identified Raman processes activated by twisted bilayer graphene superlattice.
      The dependence also reveals the strong impact of electronic-band overlaps of the
      two graphene layers. Another new mode at ~52 cm(-1), not observed previously in
      the bilayer graphene system, is tentatively attributed to a torsion mode in which
      the bottom and top graphene layers rotate out-of-phase in the plane.

PMID- 23859122
TI  - Correlation of structural order, anomalous density, and hydrogen bonding network
      of liquid water.
AB  - We use extensive molecular dynamics simulations employing different state-of-the
      art force fields to find a common framework for comparing structural orders and
      density anomalies as obtained from different water models. It is found that the
      average number of hydrogen bonds correlates well with various order parameters as
      well as the temperature of maximum densities across the different models,
      unifying apparently disparate results from different models and emphasizing the
      importance of hydrogen bonding in determining anomalous properties and the
      structure of water. A deeper insight into the hydrogen bond network of water
      reveals that the solvation shell of a water molecule can be defined by
      considering only those neighbors that are hydrogen-bonded to it. On the basis of
      this view, the origin of the appearance of a non-tetrahedral peak at a higher
      temperature in the distribution of tetrahedral order parameters has been
      explained. It is found that a neighbor that is hydrogen-bonded to the central
      molecule is tetrahedrally coordinated even at higher temperatures. The non
      tetrahedral peak at a higher temperature arises due to the strained orientation
      of the neighbors that are non-hydrogen-bonded to the central molecule. With the
      new definition of the solvation shell, liquid water can be viewed as an
      instantaneously changing random hydrogen-bonded network consisting of differently
      coordinated hydrogen-bonded molecules with their distinct solvation shells. The
      variation of the composition of these hydrogen-bonded molecules against
      temperature accounts for the density anomaly without introducing the concept of
      large-scale structural polyamorphism in water. 

PMID- 23859123
TI  - Rumination and specificity of autobiographical memory in dysphoria.
AB  - Low autobiographical memory specificity has been a commonly recurring phenomenon
      in depression. Difficulty in remembering specific details in autobiographical
      memory tests has been related to rumination, although the nature of this relation
      is not clear yet. In the present study, we evaluated differences in overgeneral
      memory patterns between dysphoric (n=65) and nondysphoric participants (n=74)
      using a free-recall method that may be more suitable for detecting overgeneral
      memory patterns than previously used methods. Furthermore, this study examined
      whether a specific maladaptive component of rumination (i.e., brooding response
      style) is particularly related to autobiographical memory patterns in depression.
      Our results showed that dysphoric participants reported less positive specific
      memories, and more extended and categoric memories than nondysphoric individuals.
      Furthermore, correlation analyses showed that the maladaptive component of
      rumination (i.e., brooding), but not the adaptive component of rumination (i.e.,
      reflection), was specifically associated to the reduced autobiographical memory
      specificity found in dysphoric participants. 

PMID- 23859124
TI  - Chitinases: in agriculture and human healthcare.
AB  - Biological control of phytopathogenic fungi and insects continues to inspire the
      research and development of environmentally friendly bioactive alternatives.
      Potentially lytic enzymes, chitinases can act as a biocontrol agent against
      agriculturally important fungi and insects. The cell wall in fungi and protective
      covers, i.e. cuticle in insects shares a key structural polymer, chitin, a beta
      1,4-linked N-acetylglucosamine polymer. Therefore, it is advantageous to develop
      a common biocontrol agent against both of these groups. As chitin is absent in
      plants and mammals, targeting its metabolism will signify an eco-friendly
      strategy for the control of agriculturally important fungi and insects but is
      innocuous to mammals, plants, beneficial insects and other organisms. In
      addition, development of chitinase transgenic plant varieties probably holds the
      most promising method for augmenting agricultural crop protection and
      productivity, when properly integrated into traditional systems. Recently, human
      proteins with chitinase activity and chitinase-like proteins were identified and
      established as biomarkers for human diseases. This review covers the recent
      advances of chitinases as a biocontrol agent and its various applications
      including preparation of medically important chitooligosaccharides, bioconversion
      of chitin as well as in implementing chitinases as diagnostic and prognostic
      markers for numerous diseases and the prospect of their future utilization.

PMID- 23859125
TI  - Management of large median and lateral intravesical lobes during robot-assisted
      radical prostatectomy.
AB  - PURPOSE: To describe a technique to manage large intravesical prostate lobes
      (IVPL) during robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS:
      We used a "rescue stitch" to retract large IVPLs anteriorly out of the bladder
      lumen. This stitch is a 6-inch long 0-polyglactin suture on a CT-1 needle with a
      Hem-o-lok clip tied to the tail end. We deployed this through the IVPL from
      distal to proximal allowing the Hem-o-lok clip to sit against the lobe's distal
      aspect. The suture is grasped and pulled toward the symphysis, delivering the
      IVPL from the bladder lumen providing an unobstructed view of the posterior
      bladder neck (BN). RESULTS: This was performed in 15 patients. Median (range)
      time to prepare and deploy the stitch(es) was 2 (0.5-3) and 5 (2-15) minutes,
      respectively. Five patients required >1 stitch. BN reconstruction was not needed.
      No patient had a positive margin at the BN. CONCLUSIONS: Deploying a stitch
      allows anterior dynamic retraction of the prostate, facilitating the dissection
      of the posterior BN.

PMID- 23859127
TI  - Fungicide contamination reduces beneficial fungi in bee bread based on an area
      wide field study in honey bee, Apis mellifera, colonies.
AB  - Fermentation by fungi converts stored pollen into bee bread that is fed to honey
      bee larvae, Apis mellifera, so the diversity of fungi in bee bread may be related
      to its food value. To explore the relationship between fungicide exposure and bee
      bread fungi, samples of bee bread collected from bee colonies pollinating
      orchards from 7 locations over 2 years were analyzed for fungicide residues and
      fungus composition. There were detectable levels of fungicides from regions that
      were sprayed before bloom. An organic orchard had the highest quantity and
      variety of fungicides, likely due to the presence of treated orchards within
      bees' flight range. Aspergillus, Penicillium, Rhizopus, and Cladosporium
      (beneficial fungi) were the primary fungal isolates found, regardless of habitat
      differences. There was some variation in fungal components amongst colonies, even
      within the same apiary. The variable components were Absidia, Alternaria,
      Aureobasidium, Bipolaris, Fusarium, Geotrichum, Mucor, Nigrospora, Paecilomyces,
      Scopulariopsis, and Trichoderma. The number of fungal isolates was reduced as an
      effect of fungicide contamination. Aspergillus abundance was particularly
      affected by increased fungicide levels, as indicated by Simpson's diversity
      index. Bee bread showing fungicide contamination originated from colonies, many
      of which showed chalkbrood symptoms. 

PMID- 23859128
TI  - The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence
      based guidelines and clinical consensus best practice guidance: a report from the
      International Restless Legs Syndrome Study Group.
AB  - A Task Force was established by the International Restless Legs Syndrome Study
      Group (IRLSSG) to develop evidence-based and consensus-based recommendations for
      the long-term pharmacologic treatment of restless legs syndrome/Willis-Ekbom
      disease (RLS/WED). The Task Force reviewed the results of all studies of RLS/WED
      treatments with durations of 6 months or longer presented at meetings over the
      past 2 years, posted on Web sites of pharmaceutical companies, or published in
      peer-reviewed journals, asking the questions, "What is the efficacy of this
      treatment in patients with RLS/WED?" and "What is the safety of this treatment in
      patients with RLS/WED?" The Task Force developed guidelines based on their review
      of 61 papers meeting inclusion criteria, and using a modified evidence-grading
      scheme. Pregabalin has been established as effective for up to 1 year in treating
      RLS/WED (Level A evidence). Pramipexole, ropinirole, and rotigotine have been
      established as effective for up to 6 months in treating RLS/WED (Level A). The
      following drugs have been established as probably effective (Level B) in treating
      RLS/WED for durations ranging from 1 to 5 years: gabapentin enacarbil,
      pramipexole, and ropinirole (1 year); levodopa (2 years); and rotigotine (5
      years). Because of associated safety concerns, pergolide and cabergoline should
      not be used in the treatment of RLS/WED unless the benefits clearly outweigh the
      risks. Other pharmacologic therapies have insufficient evidence to support their
      long-term use in treating RLS/WED. The IRLSSG Task Force also developed consensus
      based strategies for the prevention and treatment of complications (such as
      augmentation, loss of efficacy, excessive daytime sleepiness, and impulse control
      disorders) that may develop with the long-term pharmacologic treatment of
      RLS/WED. The use of either a dopamine-receptor agonist or alpha2delta calcium
      channel ligand is recommended as the first-line treatment of RLS/WED for most
      patients, with the choice of agent dependent on the patient's severity of RLS/WED
      symptoms, cognitive status, history, and comorbid conditions.

PMID- 23859129
TI  - The effect of ligand lipophilicity on the nanoparticle encapsulation of Pt(IV)
      prodrugs.
AB  - In an effort to expand the therapeutic range of platinum anticancer agents,
      several new approaches to platinum-based therapy, including nanodelivery, are
      under active investigation. To better understand the effect of ligand
      lipophilicity on the encapsulation of Pt(IV) prodrugs within polymer
      nanoparticles, the series of compounds cis,cis,trans-[Pt(NH3)2Cl2L2] was
      prepared, where L = acetate, propanoate, butanoate, pentanoate, hexanoate,
      heptanoate, octanoate, nonanoate, and decanoate. The lipophilicities of these
      compounds, assessed by reversed-phase HPLC, correlate with the octanol/water
      partition coefficients of their respective free carboxylic acid ligands, which in
      turn affect the degree of encapsulation of the Pt(IV) complex within the
      hydrophobic core of poly(lactic-co-glycolic acid)-block-poly(ethylene glycol)
      (PLGA-PEG-COOH) nanoparticles. The most lipophilic compound investigated,
      cis,cis,trans-[Pt(NH3)2Cl2(O2C(CH2)8CH3)2], displayed the best encapsulation.
      This compound was therefore selected to evaluate the effect of increased platinum
      concentration on encapsulation. As the platinum concentration was increased,
      there was an initial increase in encapsulation followed by a decrease due to
      macroscopic precipitation. Maximal loading occurred when the platinum complex was
      present at a 40% w/w ratio with respect to polymer during the nanoprecipitation
      step. Particles formed under these optimal conditions had diameters of
      approximately 50 nm, as determined by transmission electron microscopy. 

PMID- 23859130
TI  - Synthesis of a single G-quartet platform in water.
AB  - For over 50 years the G-quartet has been a defining self-assembled structure in
      biology and non-covalent synthesis. It is shown here for the first time that the
      G-quartet is isolatable in water in the absence of stabilizing G-quartet stacking
      or cations through the construction of a phosphate-linked template-assembled
      synthetic G-quartet. Synthetic design has facilitated preservation of the guanine
      base, ribose sugar, and phosphate components with correct linkage chemistry
      relative to G-quadruplex DNA. Thus, a minimal synthetic model of G-quadruplex
      DNA, as in that associated with human gene promoter or telomere regions, is
      represented by this system. An application as a probe for interactions between G
      quadruplex DNA and potential anticancer therapeutical binding ligands is
      demonstrated. Binding constants of 10(5)-10(7) M(-1) magnitude and 1:1
      stoichiometries for TMPyP4, piper, and azatrux ligands were determined, whereas
      perturbations in BSU1051 and BRACO19 ligand signal were not observed. These data
      suggest a unique test for critical end-stacking interactions at the exclusion of
      intercalative or looping interactions for G-quadruplex binding ligands. 

PMID- 23859131
TI  - Measuring recovery: validity of the "Recovery Process Inventory" and the
      "Recovery Attitudes Questionnaire".
AB  - Considerable lack of publications and inconsistent results on construct validity
      make it difficult to choose an appropriate instrument to measure recovery. The
      aim of the present study was to evaluate additional psychometric aspects of two
      established measures of personal recovery with differing focuses. Bivariate
      associations of the recovery measures with personal, clinical and subjective
      factors were conducted as indicators of concurrent (convergent and divergent)
      validity. The scales were also tested concerning internal consistency. The sample
      comprised of 81 inpatients on an acute psychiatric ward (main diagnoses: 27%
      substance-related disorders, 27% schizophrenic disorders, 25% affective
      disorders, 10% neurotic or stress-related disorders, and 11% personality
      disorders). The "Recovery Attitudes Questionnaire (RAQ)" has to be reevaluated
      before further administration due to serious psychometric shortcomings concerning
      internal consistency and concurrent validity. The "Recovery Process Inventory
      (RPI)" total scale showed acceptable concurrent and within-scale validity and can
      be recommended in order to measure the personal recovery process for clinical and
      scientific purposes.

PMID- 23859132
TI  - Laparoscopic radiofrequency ablation for traumatic splenic rupture.
AB  - BACKGROUND: Laparotomy was formerly the routine approach for treating traumatic
      splenic rupture. Traumatic splenic rupture has traditionally been treated with
      open splenectomy. The advent of laparoscopy and radiofrequency ablation (RFA) has
      ushered in new approaches to this surgical problem. The purpose of this study was
      to evaluate the use of laparoscopic RFA to treat traumatic splenic rupture.
      METHODS: Four patients with traumatic splenic ruptures underwent laparoscopic RFA
      assisted spleen-preserving surgery between September 2011 and April 2012. RFA
      electrodes were used for traumatic rupture repair or partial splenectomies using
      classic laparoscopic procedures. Safety and efficacy parameters were documented,
      including surgery time, intraoperative blood loss, postoperative drainage
      quantities, and recovery conditions. RESULTS: Three patients received
      laparoscopic splenic rupture repair and one patient received a partial
      splenectomy. Three surgeries were successful, based on 1-mo follow-up with
      computerized tomography and ultrasound examinations that indicated the
      restoration of satisfactory splenic blood supply. The fourth patient received a
      laparotomy for a total splenectomy because of massive postoperative bleeding 24 h
      after surgery. CONCLUSIONS: Laparoscopic RFA-assisted spleen-preserving surgery
      is another modality that may be considered in the management of splenic trauma.
      This small sample size and limited clinical experience does not justify its use
      on a routine basis and requires additional clinical research to fully evaluate
      its efficacy in certain critical traumatic scenarios compared with traditional
      open splenectomy.

PMID- 23859133
TI  - Therapeutic strategies of iatrogenic portal vein injury after cholecystectomy.
AB  - BACKGROUND: The incidence of vascular injury after a cholecystectomy is often
      underestimated. Although injuries to the portal vein are rare, they are
      devastating. The aim of the present study was to analyze suitable therapeutic
      strategies regarding portal vein injury in the absence of biliary injury.
      MATERIALS AND METHODS: Eleven patients with portal vein injuries after
      laparoscopic or open cholecystectomy were referred to our hospital between 2004
      and 2010. The clinical presentation, diagnosis, and management of patients with
      severe portal vein injuries were reviewed. All the patients were discharged
      without outstanding clinical conditions. During retrospective analysis, these
      patients were divided into early, middle, and late stages. RESULTS: All the 11
      patients had a portal vein and/or right hepatic artery injury, but no biliary
      injuries were observed. Among these patients, different management strategies
      were managed according to the stage of the injury. Eight patients received a
      direct suture at the time of injury by an experienced hepatobiliary surgeon. Two
      patients received thrombolytic and anticoagulation therapy after cholecystectomy,
      without additional surgery. One patient received a liver transplant 3 mo after
      the injury. After long-term follow-up, these patients had no clinical conditions.
      CONCLUSIONS: Direct repair or suture is important during the early stage of
      portal vein injury. Conservative thrombolytic and anticoagulation therapy may
      serve an important role in the treatment of acute massive thrombus in portal vein
      injury during the middle stage. Liver transplantation is a salvage therapy that
      should be used during the late stage.

PMID- 23859134
TI  - Real-time instrument detection in minimally invasive surgery using radiofrequency
      identification technology.
AB  - BACKGROUND: A key part of surgical workflow recording is recognition of the
      instrument in use. We present a radiofrequency identification (RFID)-based
      approach for real-time tracking of laparoscopic instruments. METHODS: The system
      consists of RFID-tagged instruments and an antenna unit positioned on the Mayo
      stand. For reliability analysis, RFID tracking data were compared with the
      assessment of the perioperative video data of instrument changes (the reference
      standard for instrument application detection) in 10 laparoscopic
      cholecystectomies. When the tagged instrument was on the Mayo stand, it was
      referred to as "not in use." Once it was handed to the surgeon, it was considered
      to be "in use." Temporal miscounts (incorrect number of instruments "in use")
      were analyzed. The surgeons and scrub nurses completed a questionnaire after each
      operation for individual system evaluation. RESULTS: A total of 110 distinct
      instrument applications ("in use" versus "not in use") were eligible for
      analysis. No RFID tag failure occurred. The RFID detection rates were consistent
      with the period of effective instrument application. The delay in instrument
      detection was 4.2 +/- 1.7 s. The highest percentage of temporal miscounts
      occurred during phases with continuous application of coagulation current.
      Surgeons generally rated the system better than the scrub nurses (P = 0.54).
      CONCLUSIONS: The feasibility of RFID-based real-time instrument detection was
      successfully proved in our study, with reliable detection results during
      laparoscopic cholecystectomy. Thus, RFID technology has the potential to be a
      valuable additional tool for surgical workflow recognition that could enable a
      situation dependent assistance of the surgeon in the future.

PMID- 23859135
TI  - Phosphoinositide 3-kinase/Akt pathway is involved in mediating the anti
      inflammation effects of magnesium sulfate.
AB  - BACKGROUND: We sought to elucidate whether enhancing phosphoinositide 3-kinase
      (PI3K)/Akt activity is a crucial mechanism underlying the anti-inflammation
      effects of magnesium sulfate (MgSO4). MATERIALS AND METHODS: Murine macrophages
      (RAW264.7 cells) were stimulated with endotoxin, endotoxin plus MgSO4, or
      endotoxin plus MgSO4 plus PI3K inhibitor (LY294002 or wortmannin). Control groups
      were run simultaneously. After harvesting, we assayed the expression of
      inflammatory mediators, transcriptional factor nuclear factor kappaB (NF-kappaB),
      and Akt. RESULTS: MgSO4 significantly attenuated endotoxin-induced upregulation
      of inflammatory mediators and NF-kappaB, as macrophages treated with endotoxin
      plus MgSO4 had significantly lower tumor necrosis factor alpha (P = 0.022),
      macrophage inflammatory protein 2 (P = 0.040), phosphorylated (p)-NF-kappaB p65
      (P = 0.003) and p-inhibitor-kappaB (P < 0.001) concentrations as well as lower NF
      kappaB DNA binding (P = 0.001) than macrophages treated with endotoxin alone.
      Moreover, macrophages treated with endotoxin plus MgSO4 plus LY294002 or
      wortmannin had significantly higher tumor necrosis factor alpha (P = 0.013 and P
      < 0.001), macrophage inflammatory protein 2 (P = 0.023 and P = 0.003), p-NF
      kappaB p65 (P = 0.006 and P < 0.001), and p-inhibitor-kappaB (P = 0.001 and P <
      0.001) concentrations, as well as higher NF-kappaB DNA binding (P = 0.038 and P =
      0.009), than macrophages treated with endotoxin plus MgSO4, suggesting that PI3K
      inhibitors reversed these effects of MgSO4. In contrast, macrophages treated with
      endotoxin plus MgSO4 had significantly higher p-Akt concentration than
      macrophages treated with endotoxin alone (P = 0.004). Moreover, macrophages
      treated with endotoxin plus MgSO4 also had significantly higher p-Akt
      concentration than macrophages treated with endotoxin plus MgSO4 plus LY294002 or
      wortmannin (P = 0.004 and P < 0.001). CONCLUSIONS: Enhancing PI3K/Akt activity is
      a crucial mechanism underlying the anti-inflammation effects of MgSO4.

PMID- 23859137
TI  - The roles of vitamin D in seborrhoeic keratosis: possible genetic and cellular
      signalling mechanisms.
AB  - OBJECTIVE: We review the relationship between vitamin D and seborrhoeic keratosis
      (SK). METHODS: Review literature from MEDLINE. RESULTS: Vitamin D3
      supplementation can improve SK lesions. Genetics-based studies have identified
      the proteins that link vitamin D to SK pathology. Vitamin D also exerts its
      effect on SK through cell signalling mechanisms. CONCLUSION: Vitamin D plays a
      role in SK. Calcitriol is the best form of vitamin D for use in patients with SK
      because it is the active form of the vitamin D3 metabolite and its receptors are
      present in the skin. Further investigation of the effects of calcitriol in
      patients with SK is warranted.

PMID- 23859136
TI  - Loss of beta-arrestin 2 exacerbates experimental autoimmune encephalomyelitis
      with reduced number of Foxp3+ CD4+ regulatory T cells.
AB  - beta-Arrestins are well-known regulators and mediators of G protein-coupled
      receptor signalling, and accumulating evidence reveals that they are functionally
      involved in inflammation and autoimmune diseases. Of the two beta-arrestins, beta
      arrestin 1 is documented to play regulatory roles in an animal model of multiple
      sclerosis (MS), whereas the role of beta-arrestin 2 is less clear. Here, we show
      that beta-arrestin 2-deficient mice displayed the exacerbated and sustained
      symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model of
      MS. At the cellular level, deficiency of beta-arrestin 2 led to a decreased
      number of Foxp3(+) CD4(+) regulatory T (Treg) cells in peripheral lymphoid organs
      of EAE mice. Consistently, our in vitro observations also revealed that loss of
      beta-arrestin 2 impaired the conversion of Foxp3(-) CD4(+) T cells into Foxp3(+)
      CD4(+) inducible Treg cells. Taken together, our data suggest that beta-arrestin
      2 plays a regulatory role in MS, that is opposite to that of beta-arrestin 1, in
      autoimmune diseases such as MS, which is at least partially through regulation of
      iTreg cell differentiation.

PMID- 23859138
TI  - Asthma knowledge, subjective assessment of severity and symptom perception in
      parents of children with asthma.
AB  - OBJECTIVES: This study aimed to confirm the tendency for parents to underestimate
      the severity of symptoms and the poor consistency between parents' reports of
      symptoms and the physicians' evaluation of asthma control. Additionally, the
      relationship between parents' asthma knowledge and their report of symptoms and
      estimation of asthma severity was explored. METHODS: Fifty children (M = 10.5
      years) and their caregivers were recruited from two Portuguese hospitals. A
      measure of asthma symptoms report (Severity of Chronic Asthma, SCA) and a
      subjective evaluation of asthma severity were collected and compared with
      physicians' ratings of asthma control, as well as parents' knowledge about asthma
      (Asthma Knowledge Questionnaire, AKQ) and emotional disturbance (Brief Symptom
      Inventory, BSI). RESULTS: Although parents' evaluation of perceived asthma
      severity was moderately correlated to symptoms reported, results confirm an
      inconsistency between parents' reports of symptoms, their subjective rating of
      asthma severity and the physician's rating of clinical control, revealing a
      tendency for parents to underestimate disease severity and to underreport asthma
      symptoms. Asthma knowledge was not significantly correlated to SCA or to parents'
      subjective evaluation of asthma severity. Parents with poorer knowledge reported
      fewer symptoms. CONCLUSIONS: Portuguese parents revealed a tendency to
      overestimate their child's level of asthma control and a low level of asthma
      knowledge. Parents' education, psychological disturbance and time since diagnosis
      were associated with asthma knowledge. Parents' knowledge was not related to the
      child's asthma outcomes or to their subjective evaluation of asthma severity or
      symptoms reports. Parents' asthma knowledge deficits, underreporting of symptoms
      and underestimation of asthma severity, may affect parent-provider communication
      and impede asthma control.

PMID- 23859139
TI  - Acceleration of myofiber formation in culture by a digitized synaptic signal.
AB  - Developing myofibers require chemical and electrical stimulation to induce
      functional muscle tissue. Tissue engineering protocols utilize either or both of
      these to initiate differentiation ex vivo. Current methodologies typically
      deliver multi-volt electrical signals, which may be hazardous to developing
      tissues. In attempts to mimic in vivo muscle development, we stimulated cultured
      muscle precursor cells with a low-voltage (1 mV) digitized synaptic signal
      derived from cultured cortical neurons. This synaptic signal induced larger and
      more adherent myofibers, along with markers of myoblast differentiation, compared
      to those induced following stimulation with a conventional (28 V) square signal.
      These findings suggest that stimulation with a digitized synaptic signal may be
      useful in tissue engineering and physical therapy. 

PMID- 23859140
TI  - Thermal switching of the reflection in chiral nematic mesoporous organosilica
      films infiltrated with liquid crystals.
AB  - Materials that undergo stimulus-induced optical changes are important for many
      new technologies. In this paper, we describe a new free-standing silica-based
      composite film that exhibits reversible thermochromic reflection, induced by a
      liquid crystalline guest in the pores of iridescent mesoporous films. We
      demonstrate that selective reflection from the novel mesoporous organosilica
      material with chiral nematic organization can be reversibly switched by thermal
      cycling of the 8CB guest between its isotropic and liquid crystalline states,
      which was proven by solid-state NMR experiments. The switching of the optical
      properties of the chiral solid-state host by stimulus-induced transitions of the
      guest opens the possibility of applications for these novel materials in sensors
      and displays. 

PMID- 23859141
TI  - Effects of vehicle front-end stiffness on rear seat dummies in NCAP and FMVSS208
      tests.
AB  - OBJECTIVE: This study is devoted to quantifying changes in mass and stiffness of
      vehicles tested by the National Highway Traffic Safety Administration (NHTSA)
      over the past 3 decades (model years 1982 to 2010) and understanding the effect
      of those changes on protection of rear seat occupants. METHODS: A total of 1179
      tests were used, and the changes in their mass and stiffness versus their model
      year was quantified. Additionally, data from 439 dummies tested in rear seats of
      NHTSA's full frontal crashes were analyzed. Dummies were divided into 3 groups
      based on their reference injury criteria. Multiple regressions were performed
      with speed, stiffness, and mass as predicting variables for head, neck, and chest
      injury criteria. RESULTS: A significant increase in mass and stiffness over model
      year of vehicles was observed, for passenger cars as well as large platform
      vehicles. The result showed a significant correlation (P-value < .05) between the
      increase in stiffness of the vehicles and increase in head and chest injury
      criteria for all dummy sizes. CONCLUSIONS: These results explain that stiffness
      is a significant contributor to previously reported decreases in protection of
      rear seat occupants over model years of vehicles.

PMID- 23859142
TI  - Multidetection of paralytic, diarrheic, and amnesic shellfish toxins by an
      inhibition immunoassay using a microsphere-flow cytometry system.
AB  - The presence of paralytic shellfish poisoning (PSP), diarrheic shellfish
      poisoning (DSP), and amnesic shellfish poisoning (ASP) toxins in seafood is a
      severe and growing threat to human health. In order to minimize the risks of
      human exposure, the maximum content of these toxins in seafood has been limited
      by legal regulations worldwide. The regulated limits are established in
      equivalents of the main representatives of the groups: saxitoxin (STX), okadaic
      acid (OA), and domoic acid (DA), for PSP, DSP, and ASP, respectively. In this
      study a multidetection method to screen shellfish samples for the presence of
      these toxins simultaneously was developed. Multiplexing was achieved using a
      solid-phase microsphere assay coupled to flow-fluorimetry detection, based on the
      Luminex xMap technology. The multidetection method consists of three simultaneous
      competition immunoassays. Free toxins in solution compete with STX, OA, or DA
      immobilized on the surface of three different classes of microspheres for binding
      to specific monoclonal antibodies. The IC50 obtained in the buffer was similar in
      single- and multidetection: 5.6 +/- 1.1 ng/mL for STX, 1.1 +/- 0.03 ng/mL for OA,
      and 1.9 +/- 0.1 ng/mL for DA. The sample preparation protocol was optimized for
      the simultaneous extraction of STX, OA, and DA with a mixture of methanol and
      acetate buffer. The three immunoassays performed well with mussel and scallop
      matrixes displaying adequate dynamic ranges and recovery rates (around 90% for
      STX, 80% for OA, and 100% for DA). This microsphere-based multidetection
      immunoassay provides an easy and rapid screening method capable of detecting
      simultaneously in the same sample three regulated groups of marine toxins. 

PMID- 23859144
TI  - Authenticity and scientific integrity in qualitative research.

PMID- 23859143
TI  - New alternative anticoagulants in atrial fibrillation: the move beyond warfarin.
AB  - Given the increasing prevalence of atrial fibrillation, the need for safe and
      effective stroke prophylaxis will continue to rise. Warfarin has been around for
      many years and has proven efficacy in preventing stroke, but it has major
      limitations due to its variable dosing, food and drug interactions, and
      requirement for regular monitoring. Newer agents which include dabigatran,
      rivaroxaban, and apixaban have recently or will soon be available and may provide
      an improved efficacy in stroke prevention, an improved safety profile, and
      improved user-friendliness. Dabigatran was the first of the agents to be widely
      available, and in the RE-LY study, dabigatran (150 mg dose) showed superiority to
      warfarin in preventing ischemic stroke and a significant reduction in
      intracranial bleeding. Rivaroxaban was studied in the ROCKETAF trial, and with
      once daily dosing, it showed noninferiority to warfarin in preventing stroke with
      a significant reduction in intracranial bleeding. The ARISTOTLE trial showed
      apixaban was superior to warfarin for stroke prevention, significantly reduced
      all major bleeding, and resulted in a significant reduction in all-cause
      mortality. While all three trials have important limitations, they were very
      large randomized trials with more than 14,000 patients each and show a clear
      overall net clinical benefit when compared with warfarin. Key features of the
      drugs as well as an individual's preferences and stability on warfarin will help
      guide the ultimate drug choice for any given patient, but these newer
      anticoagulant agents are likely to usher in a new era in stroke prevention in
      atrial fibrillation. 

PMID- 23859145
TI  - Research collaboration benefits everyone.

PMID- 23859146
TI  - How teen mothers describe dating violence.
AB  - OBJECTIVE: To present voices of young women who were pregnant or new parents as
      they shared their thoughts on the risks, behaviors, and prevention of teen dating
      violence (TDV). DESIGN: Descriptive, qualitative analysis. SETTING: Focus groups
      in schools designed expressly for the needs of young women who are pregnant and
      parenting. PARTICIPANTS: Twenty-six young mothers participated in one of three
      focus groups. METHODS: Focus groups explored perceptions of several dimensions of
      intimate partner violence within the context of pregnancy and parenting. A semi
      structured interview guide provided the medium to delve into young mothers'
      thoughts and perspectives about TDV. RESULTS: Data were organized in four major
      typologies: describing TDV, increasing the risk, why violence, and prevention of
      TDV. CONCLUSIONS: This analysis provides important insights into young mothers'
      lives when teen parenting and violence intersect. Rich data provide the
      foundation to expand awareness and inform programs and policies designed to
      address TDV in young women who are pregnant and parenting. Findings may be used
      by nurses to assess risk, identify teens in violent relationships, and provide
      for understanding of TDV from the perspectives of young women who are pregnant
      and parenting.

PMID- 23859147
TI  - Does a first-born female child bring mood risks to new Asian American mothers?
AB  - OBJECTIVE: To define the relationship between gender of the first-born child and
      mood in Asian American mothers. DESIGN: A secondary analysis was used to address
      the objectives of the study. SETTING: The sample was obtained from the Pregnancy
      Risk Assessment Monitoring System (PRAMS) of 40 states in the United States.
      PARTICIPANTS: The sample included 1,310 women of Asian origin who delivered their
      first children during the prior 2- to 4-month period. METHODS: Based on data from
      the PRAMS survey mailed 2- to 4-months postpartum, participants were selected for
      inclusion in the study sample from those who had given birth to their first
      children and were of Chinese, Japanese, Filipino, or other Asian origin. Chi
      squared analyses and an independent sample t test were used to assess the
      relationship between the child's sex and the mother's response to three PRAM mood
      questions; a single score was generated by summing the responses to the three
      questions. RESULTS: There were no significant (p > .05) differences in rate of
      mood symptoms or the means of the aggregated score related to a child's gender.
      CONCLUSION: The study findings are similar to those reported in the United
      Kingdom and suggest that the cultural preference for a son is not a significant
      mood risk in Asian American women.

PMID- 23859148
TI  - Current resources for evidence-based practice July/August 2013.

PMID- 23859149
TI  - Highly potent and selective nonsteroidal dual inhibitors of CYP17/CYP11B2 for the
      treatment of prostate cancer to reduce risks of cardiovascular diseases.
AB  - Dual CYP17/CYP11B2 inhibitors are proposed as a novel strategy for the treatment
      of prostate cancer to reduce risks of cardiovascular diseases. Via a combination
      of ligand- and structure-based approaches, a series of dual inhibitors were
      designed leading to the 2-(3-pyridyl)naphthalenes 10 and 11 with strong
      inhibition of both enzymes (IC50 values around 20 nM) and excellent selectivities
      over CYP11B1, CYP19, and CYP3A4. These compounds are considered as promising
      candidates for further in vivo evaluation. 

PMID- 23859150
TI  - A thermostable trypsin inhibitor with antiproliferative activity from small pinto
      beans.
AB  - Small pinto bean is a cultivar of Phaseolus vulgaris. It produces a 16-kDa
      trypsin inhibitor that could be purified using anion exchange and size
      chromatography. Q-Sepharose, Mono Q and Superdex 75 columns were employed for the
      isolation process. Small pinto bean trypsin inhibitor demonstrated moderate pH
      stability (pH 2-10) and marked heat stability, with its trypsin inhibitory
      activity largely retained after exposure to 100  degrees C for half an hour. The
      activity was abolished in the presence of dithiothreitol, in a dose-dependent
      manner, implying that disulfide bonds in small pinto bean trypsin inhibitor are
      crucial for the activity. The trypsin inhibitor showed a blocked N-terminus. The
      trypsin inhibitor only slightly inhibited the viability of breast cancer MCF7 and
      hepatoma HepG2 cells at 125 MUM.

PMID- 23859151
TI  - Synthesis of new N,N'-bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine
      dihydrochlorides and evaluation of their cytotoxicity against human hepatoma and
      breast cancer cells.
AB  - N,N'-Bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides were
      synthesized by the reaction of 2 mols of 1-aryl-3-(piperidine-1-yl)-1-propanone
      hydrochlorides with 1 mol of hydrazine hydrate. Aryl part was C6H5 (P1), 4
      CH3C6H4 (P2), 4-CH3OC6H4 (P3), 4-HOC6H4 (P4), 4-ClC6H4 (P5), 3-CH3OC6H4 (P6), 4
      FC6H4 (P7) and 4-BrC6H4 (P8). Except P1, all compounds were reported for the
      first time. The chemical structures were confirmed by UV, (1)H NMR, (13)C NMR and
      HRMS spectra. P1, P2, P7 and P8 against human hepatoma (Huh7) cells and P1, P2,
      P4, P5, P6, P7 and P8 against breast cancer (T47D) cells have shown cytotoxicity.
      P1, P2 and P7 had more potent cytotoxicity against Huh7 cells than the reference
      compound 5-FU, whereas only P2 was more potent than the 5-FU against T47D cells.
      Representative compound P7 inhibited the mitochondrial respiration at 144, 264
      and 424 uM concentrations dose-dependantly in liver homogenates. The results
      suggest that P1, P2, P7 and P8 may serve as model compounds for further synthetic
      studies.

PMID- 23859152
TI  - Synthesis and biological evaluation of novel antiviral agents as protein-protein
      interaction inhibitors.
AB  - In continuation of our research efforts toward the identification and
      optimization for novel inhibitors of interaction between human immunodeficiency
      virus type 1 integrase and cellular cofactor LEDGF/p75, we designed and
      synthesized a new series of 4-benzylindole derivatives. Most of the title
      compounds proved to be able to block this protein-protein interaction (PPI), with
      a percentage ranging from 30% to 90% at 100 uM. The most promising derivative was
      compound 10b showing IC50 value of 6.41 uM. The main structure-activity
      relationships (SAR) are discussed and rationalized by docking studies.

PMID- 23859154
TI  - Thirty minute-exposure to aged cigarette smoke increases nasal congestion in
      nonsmokers.
AB  - The aim of this study was to assess the effects of short exposures to
      experimentally aged cigarette smoke on the nose and upper airways. This crossover
      study compared the effects of 30-min exposures to (1) experimentally aged
      cigarette smoke at 1 mg/m3 particulate matter (PM)/14 ppm carbon monoxide (CO)
      and (2) conditioned filtered air on urinary metabolites of nicotine and tobacco
      specific nitrosamines. Subjective nasal symptoms were assessed by questionnaire,
      objective nasal congestion was assessed by anterior rhinomanometry and nasal
      nitric oxide (NO) concentrations were determined. Experimentally aged cigarette
      smoke is a validated model for secondhand smoke (SHS). Twenty-six healthy
      nonsmokers (10 normal, 7 atopic/nonrhinitic, 7 atopic rhinitic, 2
      nonatopic/rhinitic) were studied. A 30-min exposure to SHS increased nasal
      resistance in healthy nonsmokers. The rise in nasal resistance was most
      pronounced in rhinitic subjects. Significant increases were not noted when atopic
      subjects were considered independent of rhinitis status. Secondhand smoke
      exposure also elevated subjective nasal symptoms and urinary concentrations of
      metabolites of nicotine (cotinine and trans-3'-hydroxycotinine) and tobacco
      specific nitrosamines [(4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)] in
      all subgroups of subjects. Exposure-related, subjective nasal symptoms were
      significantly higher in rhinitic than in normal subjects. Significant changes in
      nasal NO concentrations were not detected. Data indicate a 30-min exposure to
      secondhand smoke at 1 mg/m3 PM increases subjective upper respiratory symptoms,
      increases urinary cotinine and NNAL, and produces objective nasal airflow
      obstruction in human subjects.

PMID- 23859155
TI  - Auditory clicks distort perceived velocity but only when the system has to rely
      on extraretinal signals.
AB  - Previous work has found that repetitive auditory stimulation (click trains)
      increases the subjective velocity of subsequently presented moving stimuli. We
      ask whether the effect of click trains is stronger for retinal velocity signals
      (produced when the target moves across the retina) or for extraretinal velocity
      signals (produced during smooth pursuit eye movements, when target motion across
      the retina is limited). In Experiment 1, participants viewed leftward or
      rightward moving single dot targets, travelling at speeds from 7.5 to 17.5 deg/s.
      They estimated velocity at the end of each trial. Prior presentation of auditory
      click trains increased estimated velocity, but only in the pursuit condition,
      where estimates were based on extraretinal velocity signals. Experiment 2
      generalized this result to vertical motion. Experiment 3 found that the effect of
      clicks during pursuit disappeared when participants tracked across a visually
      textured background that provided strong local motion cues. Together these
      results suggest that auditory click trains selectively affect extraretinal
      velocity signals. This novel finding suggests that the cross-modal integration
      required for auditory click trains to influence subjective velocity operates at
      later stages of processing. 

PMID- 23859153
TI  - In vivo organization of the FtsZ-ring by ZapA and ZapB revealed by quantitative
      super-resolution microscopy.
AB  - In most bacterial cells, cell division is dependent on the polymerization of the
      FtsZ protein to form a ring-like structure (Z-ring) at the midcell. Despite its
      essential role, the molecular architecture of the Z-ring remains elusive. In this
      work we examine the roles of two FtsZ-associated proteins, ZapA and ZapB, in the
      assembly dynamics and structure of the Z-ring in Escherichia coli cells. In cells
      deleted of zapA or zapB, we observed abnormal septa and highly dynamic FtsZ
      structures. While details of these FtsZ structures are difficult to discern under
      conventional fluorescence microscopy, single-molecule-based super-resolution
      imaging method Photoactivated Localization Microscopy (PALM) reveals that these
      FtsZ structures arise from disordered arrangements of FtsZ clusters. Quantitative
      analysis finds these clusters are larger and comprise more molecules than a
      single FtsZ protofilament, and likely represent a distinct polymeric species that
      is inherent to the assembly pathway of the Z-ring. Furthermore, we find these
      clusters are not due to the loss of ZapB-MatP interaction in DeltazapA and
      DeltazapB cells. Our results suggest that the main function of ZapA and ZapB in
      vivo may not be to promote the association of individual protofilaments but to
      align FtsZ clusters that consist of multiple FtsZ protofilaments. 

PMID- 23859156
TI  - Serum thymidine kinase 1 and C-reactive protein as biomarkers for screening
      clinically healthy dogs for occult disease.
AB  - Thymidine kinase (TK1) is a biomarker that correlates well with diagnosis and
      prognosis in certain canine cancers. Canine C-reactive protein (cCRP) is a widely
      accepted marker of inflammation correlated with increased risk and severity of
      various diseases. We evaluated serum TK1 and cCRP concentrations in apparently
      healthy dogs (n = 360). All dogs were followed up for a minimum of 6 months by
      health questionnaire. All dogs with cancer were identified using a proprietary
      dual-biomarker algorithm [termed Neoplasia Index (NI)]. Specificity of positive
      NI is 0.91 and high positive is 0.98. All-cause mortality was 20% in dogs with
      elevated cCRP and 3% in dogs with low cCRP. The performance of serum TK1 and cCRP
      as tools for screening for occult cancer is improved when evaluated together.
      Serum TK1 and cCRP (unified in the NI) are useful in the screening of occult
      canine cancer. cCRP is useful in screening for other serious diseases.

PMID- 23859157
TI  - Straightforward synthesis of dihydrobenzofurans and benzofurans from arynes.
AB  - Synthesis of dihydrobenzofurans was achieved by a route involving the insertion
      of arynes into formamides followed by trapping with zinc enolates of alpha
      chlorinated methines. Benzofurans were generated from dihydrobenzofurans having a
      ketone group via the addition of an ethyl anion, the retro-aldol type reaction,
      and the elimination of an amino group. 

PMID- 23859158
TI  - A dual-emission fluorescent nanocomplex of gold-cluster-decorated silica
      particles for live cell imaging of highly reactive oxygen species.
AB  - A novel nanocomplex displaying single-excitation and dual-emission fluorescent
      properties has been developed through a crown-like assembly of dye-encapsulated
      silica particles decorated with satellite AuNCs for live cell imaging of highly
      reactive oxygen species (hROS), including *OH, ClO(-) and ONOO(-). The design of
      this nanocomplex is based on our new finding that the strong fluorescence of
      AuNCs can be sensitively and selectively quenched by these hROS. The nanocomplex
      is demonstrated to have excellent biocompatibility, high intracellular delivery
      efficiency, and stability for long-time observations. The results reveal that the
      nanocomplex provides a sensitive sensor for rapid imaging of hROS signaling with
      high selectivity and contrast. 

PMID- 23859159
TI  - Secretory phospholipase A2 activity in serum and cerebrospinal fluid of patients
      with relapsing-remitting multiple sclerosis.
AB  - An increasing body of evidence suggests that patients afflicted with multiple
      sclerosis (MS) show alterations in immunologic markers including increases in
      proinflammatory cytokine activity and inflammation. Secretory Phospholipase A2
      (sPLA2) is one of the key molecules contributing to the production of
      inflammatory lipid mediators, mainly eicosanoids. They are considered
      proinflammatory enzymes and their inhibition has long been recognized as a
      desirable therapeutic target. The aim of this study was to measure the enzyme
      activity of sPLA2 both in serum and cerebrospinal fluid (CSF) of MS patients.
      Twenty MS patients accompanied with 20 age-sex matched controls were recruited.
      The results showed that the enzyme activity of serum sPLA2 was 0.007+/-0.021
      (MUmol/min/ml) in MS patients vs. 0.007+/-0.016 (MUmol/min/ml) in patients with
      other neurological diseases as a control group (P=0.5). Our findings also
      indicated that there is no correlation (P=0.6) between CSF sPLA2 enzyme activity
      and MS disease when the results of two groups were compared (0.072+/-0.020 in
      cases vs. 0.071+/-0.01 in control group). The results suggest that the enzyme
      activity of sPLA2 is not altered during the disease course.

PMID- 23859161
TI  - Burkitt lymphoma as a cause of carotidynia: imaging features. A case report.
AB  - We describe a patient with Burkitt lymphoma who developed carotidynia. MRI showed
      thickening of the walls of both common carotid arteries and PET CT showed
      increased radiotracer uptake in the same regions. MRI was essential in
      establishing the diagnosis of this rare clinical presentation. 

PMID- 23859160
TI  - Diffusion tensor magnetic resonance imaging in patients with multiple sclerosis
      and its relationship with disability.
AB  - Multiple sclerosis is a chronic inflammatory demyelinating disease of the central
      nervous system. Diffusion tensor magnetic resonance imaging (DTI) can yield
      important information on the in vivo pathological processes affecting water
      diffusion. The aim of this study was to quantitatively define water diffusion in
      normal-appearing white matter (NAWM) distant from the plaque, in the plaque, and
      around the plaque, and to investigate the correlation of these changes with
      clinical disability. Conventional MRI and DTI scans were conducted in 30 patients
      with MS and 15 healthy individuals. Fractional anisotropy maps and visible
      diffusion coefficients were created and integrated with T2-weighted images.
      Regions of interest (ROIs) were placed on the plaques on the same side, white
      matter around the plaques and NAWM on the opposite side. Only the white matter of
      healthy individuals in the control group, and FA and ADC values were obtained for
      comparison. The highest FA and lowest ADC were detected in the control group at
      the periventricular region, cerebellar peduncle and at all ROIs irrespective of
      location. There was a significant difference in comparison to the control group
      at all ROIs in patients with MS (p < 0.001 for all comparisons). No significant
      correlation between diffusion parameters and expanded disability state scale
      (EDSS) scores was found in patients with MS. DTI may provide more accurate
      information on the damage due to the illness, compared to T2A sequences, but this
      damage may not be correlated with the clinical disability measured by EDSS score.

PMID- 23859162
TI  - A case of McLeod phenotype of neuroacanthocytosis brain MR features and
      literature review.
AB  - Huntington's disease and neuroacanthocytosis may present similar clinical and MRI
      features. It is important to differentiate these findings since treatment and
      prognosis vary vastly between them. The aim of this article is to familiarize
      radiologists with the differentiating features of Huntington's disease and
      various diseases comprising neuroacanthocytosis. A 40-year-old Indian man with
      extrapyramidal symptoms was referred for MRI. The clinical diagnosis was
      Huntington's disease, but there were a few atypical clinical features such as a
      history of biting the tongue, tics, marked hyporeflexia and lower limb muscle
      wasting. MR showed atrophy of the caudate nucleus and putamen with iron
      deposition in the basal ganglia, which can be seen in Huntington's disease and in
      neuroacanthocytosis. An increased blood acanthocyte level was subsequently
      confirmed. Further work-up revealed increased serum creatine phosphokinase
      levels, normal serum lipoprotein levels and depressed K cell antigen activity on
      serological studies, confirming the diagnosis of McLeod syndrome. McLeod syndrome
      is one of the distinct phenotypes of neuroacanthocytosis. Neuroacanthocytosis is
      a group of disorders with increased serum acanthocyte counts and neurological
      involvement. Various causes of neuroacanthocytosis are discussed. It is important
      to consider the possibility of neuroacanthocytosis when features typical of
      Huntington's disease are encountered on imaging. 

PMID- 23859163
TI  - Small intracranial lipomas may be a frequent finding on computed tomography of
      the brain. A case series.
AB  - Intracranial lipomas are described as a rare finding. In this small retrospective
      analysis of 50 cases undergoing brain CT for various reasons small intracranial
      lipomas where found in nine patients. In contrast to previous reports lipomas may
      be a frequent finding on CT imaging of the brain. In particular, these small
      lipomas seem to be incidental findings lacking clinical relevance. Radiologists
      should be aware of intracranial lipomas to establish proper differential
      diagnosis. 

PMID- 23859164
TI  - Intratumoral haemorrhage causing an unusual clinical presentation of a vestibular
      schwannoma.
AB  - We present a case of an elderly woman with no history of audiological disease
      with sudden onset of visual and hearing deficits associated with systemic
      clinical signs. On examination she had impairment of right CNs from V to X. CT
      and MR imaging demonstrated a cystic vestibular schwannoma with a rare
      intralesional fluid-fluid level correlated to a recent bleed. We include high
      quality MR images to show the acute impairment of the cranial nerves next to the
      tumour after acute bleeding. Our case report includes a voxel-based morphometry
      (VMB) analysis of the tumour that, as far as we know, has never been done before
      for such a tumour. VBM analysis was performed to calculate the hypothesized
      volume changes after the acute bleed which likely resulted in a sudden increase
      in the overall size of the tumour resulting in atypical clinical signs and
      symptoms due to the establishment of a mechanical conflict with the adjacent
      cranial nerves. 

PMID- 23859165
TI  - Wernicke's encephalopathy following Hyperemesis gravidarum. A report of three
      cases.
AB  - Wernicke's encephalopathy (WE) due to causes other than chronic alcohol abuse is
      an uncommon and often misdiagnosed condition. In the setting of hyperemesis
      gravidarum, an acute deficiency of thiamine results from body stores being unable
      to meet increased metabolic demands. The condition produces typical clinical and
      radiological findings and when diagnosed early and treated promptly has a good
      prognosis. Magnetic resonance imaging (MRI) is sensitive and specific for
      diagnosis. We describe three patients with hyperemesis gravidarum who developed
      WE, and highlight a range of clinical and imaging features important for
      appropriate diagnosis. A high degree of clinical suspicion is essential.
      Treatment is often empirical pending results of investigation, and consists of
      parenteral repletion of thiamine stores. Reversal of MRI findings parallels
      clinical improvement. Neurologic outcomes are usually good, but half the
      pregnancies complicated by this condition do not produce healthy children. 

PMID- 23859166
TI  - Distribution of amyloid burden differs between idiopathic normal pressure
      hydrocephalus and Alzheimer's disease.
AB  - This study aimed to elucidate the incidence and distribution of the cortical
      retention of Pittsburgh compound B (PIB) in patients with idiopathic normal
      pressure hydrocephalus (iNPH) and clarify the differences from those in patients
      with Alzheimer's disease (AD). Ten patients with iNPH without any clinical signs
      indicative of AD were enrolled in this study. Cerebral retention of PIB in
      positron emission tomography (PET) in iNPH patients was compared with those in
      seven age-matched AD patients. The CSF levels of beta-amyloid 1-42 peptide
      (Abeta42), which inversely decrease with cerebral amyloid burden, were also
      measured. Three of the ten patients with iNPH showed increased cortical PIB
      retention. Although the mean cortical SUV ratios were similar, the distribution
      of PIB retention differed widely between the patients with iNPH and AD. PIB
      retention was limited to the high-convexity parasagittal areas in iNPH patients,
      whereas it spread over the frontal and parietotemporal areas in AD. The coronal
      images of PIB-PET were more informative than conventional transverse images in
      evaluating the distribution pattern of cortical PIB retention. Two iNPH patients
      with higher cortical PIB retention had the lowest levels of CSF Abeta42,
      indicating that PIB retention in iNPH would not reflect a simple delay in PIB
      clearance but its binding to existing Abeta amyloid in the brain. Our results
      indicate that iNPH is one of the diseases exhibiting cortical PIB retention. The
      characteristic distribution of PIB retention in iNPH could be useful in the
      differential diagnosis between iNPH and AD. 

PMID- 23859167
TI  - Neonatal dural arteriovenous fistula at the confluence presenting with paralysis
      of the orbicularis oris muscle.
AB  - A male neonate presented a dural arteriovenous fistula (DAVF) at the confluence
      with paralysis of the orbicularis oris muscle. The interesting features in our
      case were the clinical symptoms (orbicularis oris muscle paralysis at birth),
      angioarchitecture (high-flow arteriovenous shunts at the confluence) and the size
      and hemodynamic flow (mid-sized venous pouch) of the fistula. Additionally, the
      embolization technique (i.e., occipital artery approach, closing shunts with pure
      glue) automatically resulted in the immediate and complete closure of accessory
      feeders without any additional treatment, and the midterm clinical outcome was
      good. We succeeded improving the symptoms of a neonate with a congenital high
      flow DAVF by closing a fistula using a small amount of glue. 

PMID- 23859168
TI  - Traumatic labyrinthine concussion in a patient with sensorineural hearing loss.
AB  - Blunt head trauma without any temporal bone fracture or longitudinal temporal
      bone fracture, with an associated fracture of the labyrinth may cause
      labyrinthine injury with sensor neural hearing loss and vertigo because of a
      concussive injury to the membranous labyrinth. Sudden sensory neural hearing loss
      is relatively frequent. In most cases, the etiology is not discovered. One of the
      possible causes for sudden deafness is inner labyrinth bleeding or concussion,
      which were difficult to diagnose before the advent of magnetic resonance imaging.
      Vertigo without a demonstrable fracture may also be the result of labyrinthine
      concussion, cupololithiasis and perilymphatic fistula. We describe the clinical
      case of a patient with acute traumatic hearing loss and vertigo, without skull
      base fracture detected on computed tomography. Magnetic resonance study was also
      performed. We have integrated the discussion with features that allow the
      differential diagnosis from other similar conditions. 

PMID- 23859169
TI  - Stroke atlas: a 3D interactive tool correlating cerebrovascular pathology with
      underlying neuroanatomy and resulting neurological deficits.
AB  - Understanding stroke-related pathology with underlying neuroanatomy and resulting
      neurological deficits is critical in education and clinical practice. Moreover,
      communicating a stroke situation to a patient/family is difficult because of
      complicated neuroanatomy and pathology. For this purpose, we created a stroke
      atlas. The atlas correlates localized cerebrovascular pathology with both the
      resulting disorder and surrounding neuroanatomy. It also provides 3D display both
      of labeled pathology and freely composed neuroanatomy. Disorders are described in
      terms of resulting signs, symptoms and syndromes, and they have been compiled for
      ischemic stroke, hemorrhagic stroke, and cerebral aneurysms. Neuroanatomy,
      subdivided into 2,000 components including 1,300 vessels, contains cerebrum,
      cerebellum, brainstem, spinal cord, white matter, deep grey nuclei, arteries,
      veins, dural sinuses, cranial nerves and tracts. A computer application was
      developed comprising: 1) anatomy browser with the normal brain atlas (created
      earlier); 2) simulator of infarcts/hematomas/aneurysms/stenoses; 3) tools to
      label pathology; 4) cerebrovascular pathology database with lesions and
      disorders, and resulting signs, symptoms and/or syndromes. The pathology database
      is populated with 70 lesions compiled from textbooks. The initial view of each
      pathological site is preset in terms of lesion location, size, surrounding
      surface and sectional neuroanatomy, and lesion and neuroanatomy labeling. The
      atlas is useful for medical students, residents, nurses, general practitioners,
      and stroke clinicians, neuroradiologists and neurologists. It may serve as an aid
      in patient-doctor communication helping a stroke clinician explain the situation
      to a patient/family. It also enables a layman to become familiarized with normal
      brain anatomy and understand what happens in stroke. 

PMID- 23859170
TI  - Vascular cerebral anomalies associated with Septo-Optic Dysplasia. A case report.
AB  - We describe a case of Septo-Optic Dysplasia (SOD) characterized by the presence
      of anomalous cerebral vessels. In our young patient the classical features of SOD
      were associated with vascular anomalies including absence of the vein of Galen,
      right Rosenthal vein leading to the superior petrosal sinus, and anomalous origin
      of the anterior choroidal arteries. These findings have never been associated
      with SOD in the literature but their revelation supports the hypothesis of a
      vascular disruption as a possible cause of the SOD. 

PMID- 23859172
TI  - Coiling occlusion of the vertebral artery for a patient with recurrent posterior
      circulation TIAs.
AB  - Recurrent posterior circulation infarcts frequently involve multiple vascular
      territories, suggesting an embolic source. We describe a patient with left
      vertebral artery occlusion who had recurrent transient ischaemic attacks due to
      cerebral embolization originating from the occluded vertebral artery in spite of
      optimal anticoagulant and antithrombotic treatment. This was successfully managed
      by coiling occlusion of the vertebral artery with no recurrence of symptoms over
      one year of follow-up. To our knowledge, this is the first report of coiling
      occlusion in the treatment of recurrent vertebral artery embolization. 

PMID- 23859171
TI  - Endovascular treatment of cerebral aneurysms in relation to their parent artery
      wall: a single center study.
AB  - We report our two-year experience in the endovascular treatment of brain
      aneurysms in relation to their parent artery wall. We prospectively recorded
      patients with intracranial aneurysms (107 ruptured - 38 unruptured) treated with
      coiling during a two-year period: 145 patients, 94 females and 51 males - mean
      age 56 years. The aneurysms were divided into side-wall (A) and bifurcation (B)
      groups. A total occlusion rate was noted in post-embolization angiograms in 101
      aneurysms (70%) with a morbidity of 4%. No angiographic recurrence arose in the
      six-month follow-up. The two groups had a similar total occlusion rate (68.31%
      and 71.8% respectively), while the complication rate was 3% in group A and 4.7%
      in group B. Significant differences between the two groups were noted in the
      number of assisted coiling cases: 28 out of 60 cases (46.7%) in group A - 14 out
      of 85 cases (16.5%) in group B. Further statistical analysis showed strong
      dependencies for the type of endovascular procedure between the ruptured and
      unruptured aneurysms in both groups (p 0.000<0.05), but no dependencies between
      the aneurysm occlusion rate and the ruptured or non-ruptured aneurysms, or
      between the occlusion rate and the type of endovascular procedure (p 0.552>0.05
      and 0.071>0.05 respectively). In conclusion, the anatomic relation of the
      aneurysm sac with the wall of the parent artery is important, as significant
      differences in endovascular practice, devices and techniques were noted between
      side-wall and bifurcation aneurysms. 

PMID- 23859173
TI  - Treatment of middle cerebral artery occlusion and internal carotid artery
      dissection with combined mechanical thrombectomy and stenting of the internal
      carotid artery. A case report.
AB  - We describe a case of combined mechanical thrombectomy of the right middle
      cerebral artery and stent angioplasty of the right internal carotid artery in a
      severe stroke caused by arterio-arterial embolism due to a traumatic dissection
      of the internal carotid artery. The patient was admitted with an NIHSS score of
      19 and was discharged from hospital with a score of 2. Three months later
      neurological examination disclosed no pathological findings. The case
      demonstrates the crucial role of interventional procedures in the treatment of
      severe stroke where intravenous thrombolysis has little prospect of success. 

PMID- 23859174
TI  - Endovascular treatment of a large venous pouch direct carotid cavernous fistula.
AB  - Endovascular treatment of direct carotid cavernous fistula (CCF) can be performed
      by either arterial or venous approaches. The aim is to disconnect the fistula
      with or without preservation of the internal carotid artery (ICA). The aim of
      this article is to describe a technique for embolization of the cavernous sinus
      and the ICA in direct CCF using coils. Trapping the distal aspect of the fistula
      using a retrograde navigation via the vertebrobasilar system and the posterior
      communicating artery was performed in two cases. Clinical and radiological
      evolutions are described. 

PMID- 23859175
TI  - Lymphoblastic leukaemia presenting as a carotid-cavernous fistula.
AB  - A carotid-cavernous fistula is a life-threatening condition characterised by an
      abnormal communication between the carotid arterial vessels and the cavernous
      venous system. Although these fistulae can arise spontaneously, they mainly occur
      after trauma, especially road traffic accidents, falls and penetrating cranial or
      orbital injuries. The mainstay of treatment involves endovascular embolization,
      but in those patients where this is not possible or where embolization fails,
      direct surgical intervention and ligation of the artery may be necessary. Here we
      describe an interesting case of a suspected carotid-cavernous fistula which
      turned out to be cavernous sinus syndrome secondary to lymphoma. 

PMID- 23859176
TI  - Endovascular treatment of wide-neck, ruptured and unruptured aneurysms without
      supporting devices. A single center experience.
AB  - Despite of development of various supporting devices in the endovascular
      treatment (EVT) of wide-neck aneurysms, the procedure remains very challenging.
      We describe a small series of patients with relatively wide-neck aneurysms
      treated only by use of 3D coils without supporting devices. In the period July
      2011 - August 2012, we treated 23 patients with aneurysm necks > 4 mm or
      dome/neck ratios < 2. Aneurysms were located in the anterior circulation in 16
      patients and in the posterior circulation in seven. The size of aneurysms ranged
      from three to 21 mm. EVT was achieved by introducing 3D coils of different
      dimensions in a "Russian doll" fashion. Immediate angiographic results showed
      complete aneurysm obliteration in 15 patients, small neck remnant in two, and
      coil protrusion/herniation in four. In one of these cases we had an occlusion of
      the parent artery and in another case occlusion of the ascending branch (superior
      cerebellar artery), fortunately both patients remained symptom-free. Clinical
      results were excellent in 19 patients. One patient developed mild neurologic
      deficit in the treated territory immediately after the procedure; the patient
      recovered with mild hemiparesis. One patient developed a delayed stroke in
      another territory: after treatment the patient left hospital with dysphasia and
      hemiparesis. The use of 3D coils without neck supporting devices may be a useful
      alternative in selected cases of wide-neck aneurysms. Larger series with longer
      follow-up are needed to evaluate the value of this approach. 

PMID- 23859177
TI  - Estimation of CSF flow resistance in the upper cervical spine.
AB  - Chiari I patients have increased CSF velocities in the foramen magnum due
      hypothetically to increased pressure gradients or reduced flow resistance. We
      calculated flow resistance in the cervical spinal canal in a group of subjects
      with and without the Chiari malformation. Eight subjects including healthy
      volunteers and Chiari I patients were studied. From 3D high resolution MR images
      of the cervical spine mathematical models of the subarachnoid spaces were created
      by means of standard programs for segmentation and discretization. Oscillatory
      flow through the subarachnoid space was simulated. Cross-sectional area of the
      subarachnoid space was computed at each level from C1 through C4 and the length
      of this spinal canal segment was measured. Peak caudad CSF flow velocity at each
      level was plotted against cross-section area. CSF volumetric flux and resistance
      were calculated for each subject. The correlation between velocity and resistance
      was calculated. In all subjects, peak velocities increased progressively from C1
      to C4 by 0.6 to 0.7 cm/s per level. Spinal canal areas diminished from C1 to C5
      in each subject at a rate of -0.25 to -0.29 cm(2) per level. Resistance averaged
      4.3 pascal/ml/s in the eight subjects; 3.8 pascal/ml/s in patients with tonsilar
      herniation and 6.0 pascal/ml/s in volunteers. Velocity correlated inversely with
      resistance (R(2) = 0.6). CSF velocities correlated inversely with the flow
      resistance in the upper cervical spinal canal. Resistance tends to be lower in
      Chiari I patients than in healthy volunteers. 

PMID- 23859178
TI  - Progressive spinal cord compression due to epidural extramedullary hematopoiesis
      in thalassemia intermedia. A case report and literature review.
AB  - Extramedullary hematopoiesis (EMH) can occur in patients with thalassemia
      intermedia as a physiologic response to insufficient erythropoiesis to meet
      circulatory demands. Rarely, EMH involve the epidural space causing spinal cord
      compression. We describe a case of EMH in a 21-year-old man with beta-thalassemia
      intermedia presenting with progressive low back pain, worsening paraparesis and
      sphincter disturbance. Magnetic resonance imaging (MRI) demonstrated spinal cord
      compression by EMH epidural mass lesions extending from T3 to T10 levels. An
      emergency multilevel decompressive laminectomy was performed with excision of the
      masses and complete rehabilitation of the patient. 

PMID- 23859179
TI  - Opening the black box in nursing work and management practice: the role of ward
      managers.
AB  - AIM: This paper aims to identify and explore key obstacles preventing ward
      managers from effectively performing the human resource management (HRM)
      responsibilities required in their role. BACKGROUND: In the context of increasing
      costs and the decentralisation of responsibility to ward level, the relevance of
      the ward manager role within the 'black box' between human resource management
      and firm performance is becoming increasingly pertinent. METHODS: This paper
      presents an intensive case study including 37 interviews across all levels of a
      hospital where senior management attempted to shift to a high performance model
      of human resource management. RESULTS: The findings indicated that ward managers
      played a critical role in maintaining and improving employee performance,
      although they were restricted from effectively performing their responsibilities
      due to budget pressure and limited managerial skill development. CONCLUSIONS: Our
      findings support the contention that hospitals would benefit from focusing on the
      critical role of the ward manager as the central locus of influence in high
      performance human resource management (HPHRM) systems. IMPLICATIONS FOR NURSING
      MANAGEMENT: Investment into high performance human resource management is
      discouraged if the hospital cannot adequately enable ward managers who are
      responsible for implementation. Introduction of managerial skills training to
      potential and existing ward managers is critical.

PMID- 23859180
TI  - Intra- and extracranial atherosclerotic disease in acute spontaneous
      intracerebral hemorrhage.
AB  - BACKGROUND: There is little information about intracranial atherosclerotic
      disease (ICAD) and extracranial atherosclerotic disease (ECAD) in patients with
      acute spontaneous intracerebral hemorrhage (ICH). The purpose of the present
      study was to elucidate the prevalence of and the factors that correlate with ICAD
      and ECAD in patients with ICH. METHODS: A total of 274 patients with acute
      spontaneous ICH were enrolled. ICAD and ECAD (moderate to severe stenosis or
      occlusion) were mainly assessed by intracranial magnetic resonance angiography
      and carotid duplex sonography, respectively. RESULTS: Fifty-one patients (19%)
      had ICAD or ECAD; 32 had ICAD, and 21 had ECAD. On multivariable analyses, age
      (OR, 1.52; 95% CI, 1.06-2.28 for every 10 years), monocyte count (OR, 1.37; 95%
      CI, 1.02-1.87 for every 100/mm(3)), hemoglobin A1c (OR, 2.25; 95% CI, 1.08-5.15
      for every 1%), and low-density lipoprotein cholesterol levels (OR, 1.23; 95% CI,
      1.08-1.42 for every 10mg/dL) were independently associated with ICAD. Age (OR,
      2.20; 95% CI, 1.20-4.38 for 10 years) and dyslipidemia (OR, 3.95; 95% CI, 1.01
      15.97) were independently associated with ECAD. CONCLUSIONS: ICAD and ECAD were
      detected in approximately one-fifth of patients with spontaneous ICH. Age and
      dyslipidemia (or lipid profile) were associated with both ICAD and ECAD. Monocyte
      count and hemoglobin A1c were associated with ICAD.

PMID- 23859181
TI  - Noggin and Sonic hedgehog are involved in compensatory changes within the
      motoneuron-depleted mouse spinal cord.
AB  - Sonic hedgehog and Noggin are morphogenetic factors involved in neural induction
      and ventralization of the neural tube, but recent findings suggest that they
      could participate in regeneration and functional recovery after injury. Here, in
      order to verify if these mechanisms could occur in the spinal cord and involve
      synaptic plasticity, we measured the expression levels of Sonic hedgehog, Noggin,
      Choline Acetyltransferase, Synapsin-I and Glutamate receptor subunits (GluR1,
      GluR2, GluR4), in a motoneuron-depleted mouse spinal cord lesion model obtained
      by intramuscular injection of Cholera toxin-B saporin. The lesion caused
      differential expression changes of the analyzed proteins. Moreover, motor
      performance was found correlated with Sonic hedgehog and Noggin expression in
      lesioned animals. The results also suggest that Sonic hedgehog could collaborate
      in modulating synaptic plasticity. Together, these findings confirm that the
      injured mammalian spinal cord has intrinsic potential for repair and that some
      proteins classically involved in development, such as Sonic hedgehog and Noggin
      could have important roles in regeneration and functional restoration, by
      mechanisms including synaptic plasticity. 

PMID- 23859182
TI  - Effects of chitosan coatings on polypropylene mesh for implantation in a rat
      abdominal wall model.
AB  - Hernia repair and pelvic floor reconstruction are usually accompanied with the
      implantation of a surgical mesh, which frequently results in a foreign body
      response with associated complications. An ideal surgical mesh that allows force
      generation of muscle tissues without significant granulation tissue and/or
      fibrosis is of significant clinical interest. The objective of the present study
      was to evaluate the in vitro and in vivo responses of a chitosan coating on
      polypropylene mesh (Ch-PPM) in comparison with commercially available meshes. We
      found that application of a 0.5% (w/v) Ch-PPM elicited preferential attachment of
      myoblasts over fibroblast attachment in vitro. Therefore, we test the hypothesis
      that 0.5% Ch-PPM will encourage skeletal muscle tissue ingrowth and decrease
      fibrosis formation in vivo. We implanted 0.5% Ch-PPM, collagen-coated
      polypropylene mesh (PelvitexTM; C.R. Bard), and polypropylene (Avaulta Solo((r));
      C.R. Bard) alone using a rat abdominal defect model. Force generation capacity
      and inflammatory response of each mesh were evaluated 2, 4, and 12 weeks
      postimplantation. We found that chitosan coating is associated with the
      restoration of functional skeletal muscle with histomorphologic characteristics
      that resemble native muscle and an early macrophage phenotypic response that has
      previously been shown to lead to more functional outcomes. 

PMID- 23859183
TI  - Iron oxide nanoparticle toxicity testing using high-throughput analysis and high
      content imaging.
AB  - Applying validated in vitro assays to the study of nanoparticle toxicity is a
      growing trend in nanomaterial risk assessment. Precise characterisation of
      reference nanomaterials and a well-regulated in vitro testing system are required
      to determine the physicochemical descriptors which dictate the toxic potential of
      nanoparticles. The use of automated, high-throughput technologies to facilitate
      the identification and prioritisation of nanomaterials which could pose a risk is
      desirable and developments are underway. In this study, two mammalian fibroblast
      lines (Balb/c 3T3 and COS-1 cells) were treated with a range of concentrations of
      iron oxide nanomaterials manufactured for use in medical diagnostics, using an
      automated platform and high-content-imaging endpoints for cell viability,
      oxidative stress and DNA damage (double-strand breaks). At the same time, the
      high-throughput comet assay was employed to measure DNA strand breaks and
      oxidised bases. Our results show that these methods provide a fast way to
      determine the toxicity of coated and uncoated iron oxide nanoparticles and,
      furthermore, to predict the mechanism of toxicity in vitro.

PMID- 23859184
TI  - Effects of personality on risky driving behavior and accident involvement for
      Chinese drivers.
AB  - OBJECTIVE: Motor vehicle accidents are the leading cause of injury-related
      fatalities in China and pose the most serious threat to driving safety. Driver
      personality is considered as an effective predictor for risky driving behavior
      and accident liability. Previous studies have focused on the relationship between
      personality and risky driving behavior, but only a few of them have explored the
      effects of personality variables on accident involvement. In addition, few
      studies have examined the effects of personality on Chinese drivers' risky
      driving and accident involvement. The present study aimed to examine the effects
      of personality variables on Chinese drivers' unsafe driving behaviors and
      accident involvement. METHODS: Two hundred and twenty-four Chinese drivers aged
      20 to 50 were required to complete questionnaires assessing their personality
      traits (anger, sensation-seeking, altruism, and normlessness), risky driving
      behaviors (aggressive violations, ordinary violations), and accident involvement
      (all accidents, serious accidents, at-fault accidents). Multivariate regression
      analyses, adjusting for gender, age, and overall mileage, were conducted to
      identify the personality traits related to risky driving behaviors and accident
      involvement. RESULTS: Participants' personality traits were found to be
      significantly correlated with both risky driving behavior and accident
      involvement. Specifically, the traits of anger and normlessness were effective
      predictors for aggressive violations. The traits of anger, sensation-seeking,
      normlessness, and altruism were effective predictors for ordinary violations.
      Moreover, altruism and normlessness were significant predictors for the total
      number of accidents participants had during the past 3 years. CONCLUSIONS:
      Consistent with previous studies, the present study revealed that personality
      traits play an important role in predicting Chinese drivers' risky driving
      behaviors. In addition, Chinese drivers' personality characteristics were also
      associated with accident involvement.

PMID- 23859185
TI  - Transition to a smoke-free culture within mental health and drug and alcohol
      services: A survey of key stakeholders.
AB  - Tobacco smoking is common among people with mental illnesses, and they carry a
      higher burden of smoking-related illnesses. Despite this, smoke-free policies and
      systems for supporting cessation have proved difficult to introduce in mental
      health and drug and alcohol services (MHDAS). This paper examines the barriers to
      becoming smoke free within New Zealand services. Key informants, including staff,
      smoke-free coordinators, and cessation specialists were interviewed. Of the 142
      invited informants 61 agreed (42%) to participate in a telephone interview, and
      56 provided useable data. Organizations had a permissive or transitioning smoking
      culture, or were smoke free, defined by smoke-free environments, smoke-free
      promoting attitudes and behaviours of management and staff, and cessation
      support. Most organizations were on a continuum between permissive and
      transitional cultures. Only eight services had a fully smoke-free culture. MHDAS
      face many challenges in the transition to a smoke-free culture. They are not
      helped by exemptions in smoke-free policies for mental health services, staff
      smoking, negative staff attitudes to becoming smoke free, poor knowledge of
      nicotine dependence, smoking-related harm and comorbidities, and poor knowledge
      and skills regarding cessation-support options. Health inequalities will continue
      across both service and socioeconomic divides without a concerted effort to
      address smoking.

PMID- 23859186
TI  - This is an exciting time in dialysis patient safety. Introduction.

PMID- 23859187
TI  - Hemodialysis and water quality.
AB  - Over 383,900 individuals in the U.S. undergo maintenance hemodialysis that
      exposes them to water, primarily in the form of dialysate. The quality of water
      and associated dialysis solutions have been implicated in adverse patient
      outcomes and is therefore critical. The Association for the Advancement of
      Medical Instrumentation has published both standards and recommended practices
      that address both water and the dialyzing solutions. Some of these
      recommendations have been adopted into Federal Regulations by the Centers for
      Medicare and Medicaid Services as part of the Conditions for Coverage, which
      includes limits on specific contaminants within water used for dialysis,
      dialysate, and substitution fluids. Chemical, bacterial, and endotoxin
      contaminants are health threats to dialysis patients, as shown by the continued
      episodic nature of outbreaks since the 1960s causing at least 592 cases and 16
      deaths in the U.S. The importance of the dialysis water distribution system,
      current standards and recommendations, acceptable monitoring methods, a review of
      chemical, bacterial, and endotoxin outbreaks, and infection control programs are
      discussed. 

PMID- 23859188
TI  - Hepatitis C virus screening and management of seroconversions in hemodialysis
      facilities.
AB  - Over the past two decades, healthcare-associated exposure has increasingly been
      proved to be a means of hepatitis C virus (HCV) transmission, especially in
      hemodialysis facilities. The prevalence of HCV among hemodialysis patients is
      known to be several times greater than that of the general population of the
      United States, and chronic HCV infection is associated with significant morbidity
      and mortality among these patients. During 2008-2011, HCV infection outbreaks
      were identified in multiple US hemodialysis facilities, resulting in at least 46
      new HCV infections among hemodialysis patients. These outbreaks, linked to
      infection control breaches, also highlight the failure of some facilities to
      follow established guidelines for routine HCV antibody (anti-HCV) screening and
      response to new HCV infection among hemodialysis patients. Current national
      guidelines recommend screening of hemodialysis patients for anti-HCV on facility
      admission and, for susceptible patients, on a semiannual basis. Here, we seek to
      underscore the importance of compliance with national recommendations for anti
      HCV screening of hemodialysis patients and actions to be taken in the event of
      possible HCV transmission within a hemodialysis facility. These include general
      steps to ensure that: hemodialysis patients are routinely screened for anti-HCV
      to facilitate early detection of new infections; newly infected patients are
      informed of the change in their HCV status and undergo clinical evaluation; and
      public health officials are notified of new HCV infections in a timely manner. We
      then focus on the need to assess infection control practices at the facility,
      with particular attention given to safe handling of injectable medications, hand
      hygiene and disinfection practices. In the absence of a vaccine, routine
      screening and adherence to standard infection control practices will remain the
      key strategies for preventing HCV transmission in hemodialysis units.

PMID- 23859189
TI  - A systematic review of buttonhole cannulation practices and outcomes.
AB  - Buttonhole (constant site) cannulation has emerged as an attractive technique for
      needling arteriovenous fistulae. However, the balance of benefits and harms
      associated with this intervention is unclear. We conducted a systematic review of
      studies reporting outcomes with buttonhole cannulation. The setting and
      population included adult patients receiving home or center hemodialysis. We
      searched MEDLINE, Embase (1980-June 2012), and CINAHL (1997-June 2012), for
      randomized and observational studies. We also searched conference proceedings
      (2009-2011). The interventions included: 1) buttonhole cannulation established by
      sharp needles, with or without a polycarbonate peg, 2) rope-ladder cannulation.
      Outcomes of interest included: Facility practices, systemic infection, local
      infection, access survival, access interventions, access-related hospitalization,
      patient survival, pain, quality of life, and aneurysm formation. We identified 23
      full-text articles and 4 abstracts; 3 were open-label trials, and the remainder
      observational studies of varying design and methodological quality. Studies were
      predominantly descriptive and lacked direct comparisons between buttonhole and
      rope-ladder cannulation. No qualitative differences in outcomes were noted among
      home and center hemodialysis patients using buttonhole cannulation. Rates of
      bacteremia were generally higher with buttonhole cannulation. Studies reporting
      access survival, hospitalization, quality of life, pain, and aneurysm formation
      had serious methodological limitations that limited our confidence in their
      estimates of effect. Among the various facility practices that were described,
      only the application of mupirocin cream was noted to be associated with reduced
      risk of infection. Limitations in included studies were short follow-up,
      crossover designs, lack of parallel control groups, and the use of patient
      reported outcome measures that were not well validated. The main limitation of
      this review was a limited literature search. Buttonhole cannulation may be
      associated with an increased risk of infection. Larger, more definitive studies
      are needed to determine whether this technique is safe for broader use. 

PMID- 23859190
TI  - Prevention and treatment of hemodialysis-related bloodstream infections.
AB  - Despite improvements in the delivery of care, the annual all-cause mortality rate
      for end-stage renal disease (ESRD) patients is still around 220 deaths per 1000
      at risk patient-years. Infection-related causes are second only to cardiovascular
      events as a cause for mortality among ESRD patients. Almost two-thirds of all
      ESRD patients will require hemodialysis and they are at the highest risk for
      bloodstream infections. An effective method for reducing bloodstream infections
      is increasing the use of fistula for dialysis access, but, for a significant
      number of patients, catheter access is inevitable. Several interventions have
      been studied that primarily involves the application of antimicrobials at the
      catheter exit site. Other interventions include the use of antibiotic lock
      solutions, which have resulted in the development of antibiotic resistance. Novel
      connecting devices may be of use in the future, but studies are still needed to
      show their efficacy at preventing catheter-related bloodstream infections among
      hemodialysis patients. As insertion sites can be limited in hemodialysis
      patients, treatment of certain catheter-related bloodstream infections can be
      amenable to catheter retention as long as both systemic antibiotic and antibiotic
      lock therapies are also initiated. Until more data are available, catheter
      removal followed by systemic therapy is preferred for infections involving
      Staphylococcus aureus, Pseudomonas species, Enterococcus species, and Candida
      species.

PMID- 23859191
TI  - The economics of hemodialysis catheter-related infection prophylaxis.
AB  - Hemodialysis central venous catheter (CVC) use is associated with the highest
      morbidity, mortality, and cost of all types of hemodialysis vascular access. CVC
      related infection drives much of the cost associated with CVC use. The magnitude
      of the cost associated with CVC-related infection varies depending on the type
      and severity of that infection; however, estimates of the total direct and
      indirect costs associated with hospitalizations due to hemodialysis CVC-related
      infections range from 17,000 USD to 32,000 USD per episode. Thus, it is
      critically important, to not only have effective strategies to limit CVC-related
      infection but also evaluate whether these strategies are an efficient use of
      resources. Prophylactic strategies can be considered economically efficient only
      if the value of its implementation and the corresponding drop in infection rate
      offer greater value than standard care. The optimal CVC-related infection
      prophylaxis strategy should work to limit infection risk with minimal risk,
      inconvenience, and discomfort to the patient, and at minimal cost. The aim of
      this review was to examine the clinical and economic impact of some commonly
      described interventions used for CVC infection prophylaxis. 

PMID- 23859192
TI  - Prevention of peritonitis in peritoneal dialysis.
AB  - Reducing the frequency of peritonitis for patients undergoing peritoneal dialysis
      (PD) continues to be a challenge. This review focuses on recent updates in
      catheter care and other patient factors that influence infection rates. An
      experienced nursing staff plays an important role in teaching proper PD technique
      to new patients, but nursing staff must be cognizant of each patient's unique
      educational needs. Over time, many patients become less adherent to proper
      dialysis technique, such as washing hands or wearing a mask. This behavior is
      associated with higher risk of peritonitis and is modifiable with re-training.
      Prophylactic antibiotics before PD catheter placement can decrease the infection
      risk immediately after catheter placement. In addition, some studies suggest that
      prophylaxis against fungal superinfection after antibiotic exposure is effective
      in reducing fungal peritonitis, although larger randomized studies are needed
      before this practice can be recommended for all patients. Over time, exit site
      and nasal colonization with pathogenic organisms can lead to exit-site infections
      and peritonitis. For patients with Staphylococcus aureus colonization, exit-site
      prophylaxis with either mupirocin or gentamicin cream reduces clinical infection
      with this organism. Although there are limited data for support, antibiotic
      prophylaxis before gastrointestinal, gynecologic, or dental procedures may also
      help reduce the risk of peritonitis.

PMID- 23859194
TI  - Mitogen-activated protein kinase p38 and retinoblastoma protein signalling is
      required for DNA damage-mediated formation of senescence-associated
      heterochromatic foci in tumour cells.
AB  - DNA-damaging agents are able to induce irreversible cell growth arrest and
      senescence in some types of tumour cells, thus contributing to the static feature
      of cancer. However, senescent tumour cells may re-enter the cell cycle, leading
      to tumour relapse. Understanding the mechanisms that control the viability of
      senescent cells may be critical for tumour suppression. Primary human fibroblasts
      undergoing oncogene-induced or replicative senescence are known to form
      senescence-associated heterochromatin foci (SAHF), which contribute to the
      stability of the senescent state. However, it is unclear whether SAHF formation
      is universal in tumour cells. We report that the DNA-damaging agents doxorubicin
      and 7-ethyl-10-hydroxycamptothecin were able to induce the formation of SAHF in
      some tumour cell types, and this induction was accompanied by activation of the
      retinoblastoma protein pathway. By contrast, tumour cells in which the
      retinoblastoma protein pathway could not be activated by doxorubicin or 7-ethyl
      10-hydroxycamptothecin failed to form SAHF. In parallel, tumour cells with
      deficient retinoblastoma protein were also unable to form SAHF. In addition, we
      show that the mitogen-activated protein kinase p38 pathway was involved in tumour
      cell SAHF formation in response to doxorubicin and 7-ethyl-10
      hydroxycamptothecin. Furthermore, HMG box transcription factor 1 (HBP1), a
      downstream target of the mitogen-activated protein kinase p38-mediated senescence
      pathway, was required for SAHF formation. Taken together, the results of the
      present study highlight the roles of the mitogen-activated protein kinase
      p38/retinoblastoma protein pathway in tumour cell SAHF formation in response to
      DNA-damaging agents, and provide new insights into the mechanisms of DNA damage
      mediated tumour suppression.

PMID- 23859195
TI  - Efficacy and Safety of Sofosbuvir in the Treatment of Chronic Hepatitis C: The
      Dawn of a New Era.
AB  - Hepatitis C virus (HCV) infection affects about 160 million people worldwide.
      Currently, it is treated with pegylated interferon (PEG-IFN) plus ribavirin,
      associated with a protease inhibitor in case of genotype 1 infection. However,
      this combination is often contraindicated and associated with severe adverse
      events that limit its use in clinical practice. Several drugs active against HCV
      are in an advanced phase of clinical development. Among these, sofosbuvir appears
      one of the most promising candidates for use in association with both interferon
      and interferon-free combinations. This review focuses on the results of several
      sofosbuvir-based phase III trials that have very recently become available. These
      studies show that the co-administration of sofosbuvir, PEG-IFN and ribavirin for
      12 weeks is associated with a very high rate of sustained virological responses
      (SVR) (about 90%) in naive patients with genotypes 1, 4, 5 or 6. In patients
      infected by genotypes 2 or 3, the interferon-free combination of sofosbuvir and
      ribavirin administered for 12 weeks is associated with a SVR of 97% and 56% in
      naive patients, and of 86% and 30% in experienced genotype 2 or 3 patients,
      respectively. The safety and tolerability profile is optimal and consistent with
      that of the other drugs administered in the combination (ribavirin and/or
      interferon). In conclusion, the recent phase III trials of sofosbuvir confirm the
      excellent results of phase II studies in terms of efficacy and safety and will
      probably open a new era in the fight against HCV. 

PMID- 23859196
TI  - Forward: combating resistance: infectious diseases.

PMID- 23859197
TI  - PerR: a bacterial resistance regulator and can we target it?

PMID- 23859198
TI  - Possible paths and potential barriers to successfully modeling drug resistance.

PMID- 23859199
TI  - A fresh start in the hunt for novel antibacterials.

PMID- 23859200
TI  - Anticancer drug demonstrates histone eviction activity.

PMID- 23859201
TI  - Interview with Celia Schiffer.

PMID- 23859202
TI  - Interview with Line Matthiessen.

PMID- 23859203
TI  - Resistance mechanism to an uncompetitive inhibitor of a single-substrate, single
      product enzyme: a study of Helicobacter pylori glutamate racemase.
AB  - Two independent series of inhibitors of Helicobacter pylori glutamate racemase
      (MurI) were characterized for their kinetic mechanism, and one was used to
      generate resistant mutants in vitro. Mutant MurI enzymes from these strains were
      characterized by structural, genetic, kinetic and biophysical methods. Both
      inhibitor series, pyrazolopyrimidinediones and benzodiazepines, are uncompetitive
      with respect to the glutamate substrate, and the resistance mutations were found
      to act by reducing the affinity of MurI for substrate, thereby reducing the pool
      of enzyme-substrate complex available for binding inhibitor, while still allowing
      sufficient glutamate racemase activity for peptidoglycan construction.
      Uncompetitive inhibitors of a single-substrate, single-product enzyme are rare,
      and this work gives insight into an remarkable resistance mechanism. This article
      will discuss the projected clinical impact of H. pylori MurI resistance on these
      types of inhibitors. 

PMID- 23859205
TI  - Rethinking the composition of a rational antibiotic arsenal for the 21st century.
AB  - The importance of the human microbiome in health may be the single most valuable
      development in our conception of the microbial world since Pasteur's germ theory
      of the 1860s. Its implications for our understanding of health and pathogenesis
      are profound. Coupled with the revolution in diagnostics that we are now
      witnessing - a revolution that changes medicine from a science of symptoms to a
      science of causes - we cannot continue to develop antibiotics as we have for the
      past 80 years. Instead, we need to usher in a new conception of the role of
      antibiotics in treatment: away from single molecules that target broad
      phylogenetic spectra and towards targeted molecules that cripple the pathogen
      while leaving the rest of the microbiome largely intact. 

PMID- 23859204
TI  - Understanding HIV-1 protease autoprocessing for novel therapeutic development.
AB  - In the infected cell, HIV-1 protease (PR) is initially synthesized as part of the
      GagPol polyprotein. PR autoprocessing is a virus-specific process by which the PR
      domain embedded in the precursor catalyzes proteolytic reactions responsible for
      liberation of free mature PRs, which then recognize and cleave at least ten
      different peptide sequences in the Gag and GagPol polyproteins. Despite extensive
      structure and function studies of the mature PRs as well as the successful
      development of ten US FDA-approved catalytic-site inhibitors, the precursor
      autoprocessing mechanism remains an intriguing yet-to-be-solved puzzle. This
      article discusses current understanding of the autoprocessing mechanism, in an
      effort to prompt the development of novel anti-HIV drugs that selectively target
      precursor autoprocessing. 

PMID- 23859206
TI  - Targeting metallo-beta-lactamase enzymes in antibiotic resistance.
AB  - The beta-lactam antibiotics are essential for the treatment of a wide range of
      human bacterial diseases. However, a class of zinc-dependent hydrolases known as
      the metallo-beta-lactamase (MBL) can confer bacteria with extended spectrum beta
      lactam resistance. To date, there are no clinically approved MBL inhibitors,
      making these enzymes a serious threat to human health. In this review, a
      structural approach is taken to outline some of the more promising MBL inhibitors
      and shed light on how the resistance conferred by this emerging class of enzymes
      may be circumvented in the future. 

PMID- 23859207
TI  - Small-molecule inhibition of bacterial two-component systems to combat antibiotic
      resistance and virulence.
AB  - Infections caused by multidrug-resistant bacteria are a considerable and
      increasing global problem. The development of new antibiotics is not keeping pace
      with the rapid evolution of resistance to almost all clinically available drugs,
      and novel strategies are required to fight bacterial infections. One such
      strategy is the control of pathogenic behaviors, as opposed to simply killing
      bacteria. Bacterial two-component system (TCS) signal transduction pathways
      control many pathogenic bacterial behaviors, such as virulence, biofilm formation
      and antibiotic resistance and are, therefore, an attractive target for the
      development of new drugs. This review presents an overview of TCS that are
      potential targets for such a strategy, describes small-molecules inhibitors of
      TCS identified to date and discusses assays for the identification of novel
      inhibitors. The future perspective for the identification and use of inhibitors
      of TCS to potentially provide new therapeutic options for the treatment of drug
      resistant bacterial infections is discussed. 

PMID- 23859208
TI  - Strategies to overcome the action of aminoglycoside-modifying enzymes for
      treating resistant bacterial infections.
AB  - Shortly after the discovery of the first antibiotics, bacterial resistance began
      to emerge. Many mechanisms give rise to resistance; the most prevalent mechanism
      of resistance to the aminoglycoside (AG) family of antibiotics is the action of
      aminoglycoside-modifying enzymes (AMEs). Since the identification of these
      modifying enzymes, many efforts have been put forth to prevent their damaging
      alterations of AGs. These diverse strategies are discussed within this review,
      including: creating new AGs that are unaffected by AMEs; developing inhibitors of
      AMEs to be co-delivered with AGs; or regulating AME expression. Modern high
      throughput methods as well as drug combinations and repurposing are highlighted
      as recent drug-discovery efforts towards fighting the increasing antibiotic
      resistance crisis. 

PMID- 23859210
TI  - Replacing sulfa drugs with novel DHPS inhibitors.
AB  - More research effort needs to be invested in antimicrobial drug development to
      address the increasing threat of multidrug-resistant organisms. The enzyme DHPS
      has been a validated drug target for over 70 years as the target for the highly
      successful sulfa drugs. The use of sulfa drugs has been compromised by the
      widespread presence of resistant organisms and the adverse side effects
      associated with their use. Despite the large amount of structural information
      available for DHPS, few recent publications address the possibility of using this
      knowledge for novel drug design. This article reviews the relevant papers and
      patents that report promising new small-molecule inhibitors of DHPS, and discuss
      these data in light of new insights into the DHPS catalytic mechanism and
      recently determined crystal structures of DHPS bound to potent small-molecule
      inhibitors. This new functional understanding confirms that DHPS deserves further
      consideration as an antimicrobial drug target. 

PMID- 23859213
TI  - Synthesis and electrochemical and biological studies of novel coumarin-chalcone
      hybrid compounds.
AB  - A series of novel hydroxy-coumarin-chalcone hybrid compounds 2a-i has been
      synthesized by employing a simple and efficient methodology. An electrochemical
      characterization using cyclic voltammetry and ESR spectroscopy were carried out
      to characterize the oxidation mechanism for the target compounds. The antioxidant
      capacity and reactivity were determined by ORAC and ESR assays, respectively.
      Biological assays were assessed to evaluate the cytotoxicity and cytoprotection
      capacity against ROS/RNS on BAEC. The results revealed that all tested compounds
      present ORAC values that are much higher than other well-known antioxidant
      compounds such as quercetin and catechin. Compound 2e showed the highest ORAC
      value (14.1) and also presented a low oxidation potential, good scavenging
      capacity against hydroxyl radicals, low cytotoxicity, and high cytoprotective
      activity. 

PMID- 23859209
TI  - Cyclic lipodepsipeptides: a new class of antibacterial agents in the battle
      against resistant bacteria.
AB  - In order to provide effective treatment options for infections caused by
      multidrug-resistant bacteria, innovative antibiotics are necessary, preferably
      with novel modes of action and/or belonging to novel classes of drugs. Naturally
      occurring cyclic lipodepsipeptides, which contain one or more ester bonds along
      with the amide bonds, have emerged as promising candidates for the development of
      new antibiotics. Some of these natural products are either already marketed or in
      advanced stages of clinical development. However, despite the progress in the
      development of new antibacterial agents, it is inevitable that resistant strains
      of bacteria will emerge in response to the widespread use of a particular
      antibiotic and limit its lifetime. Therefore, development of new antibiotics
      remains our most efficient way to counteract bacterial resistance. 

PMID- 23859214
TI  - Molecular characterization of the enzymes involved in the degradation of a
      brominated aromatic herbicide.
AB  - Dehalogenation is the key step in the degradation of halogenated aromatics, while
      reductive dehalogenation is originally thought to rarely occur in aerobes. In
      this study, an aerobic strain of Comamonas sp. 7D-2 was shown to degrade the
      brominated aromatic herbicide bromoxynil completely and release two equivalents
      of bromides under aerobic conditions. The enzymes involved in the degradation of
      bromoxynil to 4-carboxy-2-hydroxymuconate-6-semialdehyde, including nitrilase,
      reductive dehalogenase (BhbA), 4-hydroxybenzoate 3-monooxygenase and
      protocatechuate 4,5-dioxygenase, were molecularly characterized. The novel
      dehalogenase BhbA was shown to be a complex of a respiration-linked reductive
      dehalogenase (RdhA) domain and a NAD(P)H-dependent oxidoreductase domain and to
      have key features of anaerobic respiratory RdhAs, including two predicted binding
      motifs for [4Fe-4S] clusters and a close association with a hydrophobic membrane
      protein (BhbB). BhbB was confirmed to anchor BhbA to the membrane. BhbA was
      partially purified and found to use NAD(P)H as electron donors. Full-length bhbA
      homologues were found almost exclusively in marine aerobic proteobacteria,
      suggesting that reductive dehalogenation occurs extensively in aerobes and that
      bhbA is horizontally transferred from marine microorganisms. The discovery of a
      functional reductive dehalogenase and ring-cleavage oxygenases in an aerobe opens
      up possibilities for basic research as well as the potential application for
      bioremediation. 

PMID- 23859215
TI  - Gizzard erosion and ulceration syndrome in chickens and turkeys: a review of
      causal or predisposing factors.
AB  - Gizzard erosion and ulceration syndrome (GEU) was described for the first time in
      the 1930s. The main focus of early studies was on nutritional deficiencies and
      peroxidation of highly polyunsaturated fatty acids as causative factors. During
      the 1970s and 1980s the focus was moved towards toxic substances in the feed.
      Scott's review in 1985 concluded that overproduction of gastric acid induced by
      gizzerosine was a major cause of GEU. During the last decades, serotype 1 of fowl
      adenovirus A and Clostridium perfringens have been implicated as important
      pathogenic agents in the development of GEU in chickens. Although GEU is globally
      distributed and its subclinical form appears to be common in commercial poultry
      flocks, the condition is rarely mentioned in standard textbooks on poultry
      health. This regrettable fact is probably due in part to the lack of one
      definitive cause of the syndrome. 

PMID- 23859216
TI  - Chicken embryo lethality assay for determining the virulence of Riemerella
      anatipestifer isolates.
AB  - Riemerella anatipestifer is the causative agent of polyserositis and septicaemia
      in waterfowl. Twenty-one serotypes have been reported, and there is a strong
      variation in virulence between strains according to serotype or strain. However,
      little information is available to assess virulence, such as virulence-associated
      genes; thus, it is difficult to estimate the risk from field strains. Hence, we
      established a chicken embryo lethality assay (ELA) model to determine the
      virulence of R. anatipestifer strains. Three virulent strains (RA T1, RA T7, and
      V-1) and three avirulent strains (Av-1, Av-2, and Av-3), which were confirmed by
      duck challenge, were used to perform the ELA. Inoculating 10(2) to 10(4) colony
      forming units into the allantoic cavity of 10-day-old embryos discriminated
      between virulent and avirulent strains based on mortality. Differences in
      invasion rates into embryonic tissues were found between the RA T1 and Av-1
      strains. The maximum colony-forming units of the RA T1 strain were about 1000
      times higher than those of the Av-1 strain in the tissue invasion rate for 4
      days. We found that the virulent strains killed embryos at mortality rates >= 50%
      during the first 3 days after inoculation and that the avirulent strains had
      death rates of <= 20% over 5 days. These results obtained by repeated testing
      suggest that the ELA could be used as a first-line screening method to determine
      the virulence of R. anatipestifer strains.

PMID- 23859211
TI  - Transition-state inhibitors of purine salvage and other prospective enzyme
      targets in malaria.
AB  - Malaria is a leading cause of human death within the tropics. The gradual
      generation of drug resistance imposes an urgent need for the development of new
      and selective antimalarial agents. Kinetic isotope effects coupled to
      computational chemistry have provided the relevant details on geometry and charge
      of enzymatic transition states to facilitate the design of transition-state
      analogs. These features have been reproduced into chemically stable mimics
      through synthetic chemistry, generating inhibitors with dissociation constants in
      the pico- to femto-molar range. Transition-state analogs are expected to
      contribute to the control of malaria. 

PMID- 23859217
TI  - Meta-analysis: ARFI elastography versus transient elastography for the evaluation
      of liver fibrosis.
AB  - AIMS: This meta-analysis aims to compare the diagnostic performance of acoustic
      radiation force impulse (ARFI) elastography and transient elastography (TE) in
      the assessment of liver fibrosis using liver biopsy (LB) as 'gold-standard'.
      METHODS: PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape
      databases were searched for all studies published until 31 May 2012 that
      evaluated the liver stiffness by means of ARFI, TE and LB. Information abstracted
      from each study according to a fixed protocol included study design and
      methodological characteristics, patient characteristics, interventions, outcomes
      and missing outcome data. RESULTS: Thirteen studies (11 full-length articles and
      2 abstracts) including 1163 patients with chronic hepatopathies were included in
      the analysis. Inability to obtain reliable measurements was more than thrice as
      high for TE as that of ARFI (6.6% vs. 2.1%, P < 0.001). For detection of
      significant fibrosis, (F >= 2) the summary sensitivity (Se) was 0.74 (95% CI:
      0.66-0.80) and specificity (Sp) was 0.83 (95% CI: 0.75-0.89) for ARFI, while for
      TE the Se was 0.78 (95% CI: 0.72-0.83) and Sp was 0.84 (95% CI: 0.75-0.90). For
      the diagnosis of cirrhosis, the summary Se was 0.87 (95% CI: 0.79-0.92) and Sp
      was 0.87 (95% CI: 0.81-0.91) for ARFI elastography, and, respectively, 0.89 (95%
      CI: 0.80-0.94) and 0.87 (95% CI: 0.82-0.91) for TE. The diagnostic odds ratio of
      ARFI and TE did not differ significantly in the detection of significant fibrosis
      [mean difference in rDOR = 0.27 (95% CI: 0.69-0.14)] and cirrhosis [mean
      difference in rDOR = 0.12 (95% CI: 0.29-0.52)]. CONCLUSION: Acoustic radiation
      force impulse elastography seems to be a good method for assessing liver
      fibrosis, and shows higher rate of reliable measurements and similar predictive
      value to TE for significant fibrosis and cirrhosis.

PMID- 23859218
TI  - Synthesis of 6-Se-guanosine RNAs for structural study.
AB  - 6-Se-guanosine phosphoramidite and RNAs have been synthesized by selenium
      substitution of the 6-oxygen atom, and it is revealed that the Se-derivatization
      is relatively stable and that bulge and wobble structures can better accommodate
      a large Se atom than a duplex. This Se-modification is useful in the structural
      study of RNAs and their protein complexes. 

PMID- 23859219
TI  - Priming prepositional phrase attachment: evidence from eye-tracking and event
      related potentials.
AB  - Three syntactic-priming experiments investigated the effect of structurally
      similar or dissimilar prime sentences on the processing of target sentences,
      using eye tracking (Experiment 1) and event-related potentials (ERPs)
      (Experiments 2 and 3) All three experiments tested readers' response to sentences
      containing a temporary syntactic ambiguity. The ambiguity occurred because a
      prepositional phrase modifier (PP-modifier) could attach either to a preceding
      verb or to a preceding noun. Previous experiments have established that (a) noun
      modifying expressions are harder to process than verb-modifying expressions (when
      test sentences are presented in isolation); and (b) for other kinds of sentences,
      processing a structurally similar prime sentence can facilitate processing a
      target sentence. The experiments reported here were designed to determine whether
      a structurally similar prime could facilitate processing of noun-attached
      modifiers and whether such facilitation reflected syntactic-structure-building or
      semantic processes. These findings have implications for accounts of structural
      priming during online comprehension and for accounts of syntactic representation
      and processing in comprehension. 

PMID- 23859220
TI  - Efficient energy sensitization of C60 and application to organic photovoltaics.
AB  - Fullerenes are currently the most popular electron-acceptor material used in
      organic photovoltaics (OPVs) due to their superior properties, such as good
      electron conductivity and efficient charge separation at the donor/acceptor
      interface. However, low absorptivity in the visible spectral region is a
      significant drawback of fullerenes. In this study, we have designed a zinc
      chlorodipyrrin derivative (ZCl) that absorbs strongly in the visible region (450
      600 nm) with an optical density 7-fold higher than a C60 film. ZCl efficiently
      transfers absorbed photoenergy to C60 in mixed films. Application of ZCl as an
      energy sensitizer in OPV devices leads to an increase in the photocurrent from
      the acceptor layer, without changing the other device characteristics, i.e., open
      circuit voltage and fill factor. For example, C60-based OPVs with and without the
      sensitizer give 4.03 and 3.05 mA/cm(2), respectively, while both have V(OC) =
      0.88 V and FF = 0.44. Our ZCl sensitization approach improves the absorbance of
      the electron-acceptor layer while still utilizing the beneficial characteristics
      of C60 in OPVs.

PMID- 23859221
TI  - Convective diffusion of nanoparticles from the epithelial barrier toward regional
      lymph nodes.
AB  - Drug delivery using nanoparticles as drug carriers has recently attracted the
      attention of many investigators. Targeted delivery of nanoparticles to the lymph
      nodes is especially important to prevent cancer metastasis or infection, and to
      diagnose disease stage. However, systemic injection of nanoparticles often
      results in organ toxicity because they reach and accumulate in all the lymph
      nodes in the body. An attractive strategy would be to deliver the drug-loaded
      nanoparticles to a subset of draining lymph nodes corresponding to a specific
      site or organ to minimize systemic toxicity. In this respect, mucosal delivery of
      nanoparticles to regional draining lymph nodes of a selected site creates a new
      opportunity to accomplish this task with minimal toxicity. One example is the
      delivery of nanoparticles from the vaginal lumen to draining lymph nodes to
      prevent the transmission of HIV in women. Other known examples include mucosal
      delivery of vaccines to induce immunity. In all cases, molecular and particle
      transport by means of diffusion and convective diffusion play a major role. The
      corresponding transport processes have common inherent regularities and are
      addressed in this review. Here we use nanoparticle delivery from the vaginal
      lumen to the lymph nodes as an example to address the many aspects of associated
      transport processes. In this case, nanoparticles penetrate the epithelial barrier
      and move through the interstitium (tissue) to the initial lymphatics until they
      finally reach the lymph nodes. Since the movement of interstitial liquid near the
      epithelial barrier is retarded, nanoparticle transport was found to take place
      through special foci present in the epithelium. Immediately after nanoparticles
      emerge from the foci, they move through the interstitium due to diffusion
      affected by convection (convective diffusion). Specifically, the convective
      transport of nanoparticles occurs due to their convection together with
      interstitial fluid through the interstitium toward the initial lymph capillaries.
      Afterwards, nanoparticles move together with the lymph flow along the initial
      lymph capillaries and then enter the afferent lymphatics and ultimately reach the
      lymph node. As the liquid moves through the interstitium toward the initial lymph
      capillaries due to the axial movement of lymph along the lymphatics, the theory
      for coupling between lymph flow and concomitant flow through the interstitium is
      developed to describe this general case. The developed theory is applied to
      interpret the large uptake of Qdots by lymph nodes during inflammation, which is
      induced by pre-treating mouse vagina with the surfactant Nonoxynol-9 prior to
      instilling the Qdots. Inflammation is viewed here to cause broadening of the
      pores within the interstitium with the concomitant formation of transport
      channels which function as conduits to transport the nanoparticles to the initial
      lymph capillaries. We introduced the term "effective channels" to denote those
      channels which interconnect with foci present in the epithelial barrier and which
      function to transport nanoparticles to initial lymph capillaries. The time of
      transport toward the lymph node, predicated by the theory, increases rapidly with
      increasing the distance y0 between the epithelial barrier and the initial lymph
      capillaries. Transport time is only a few hours, when y0 is small, about some R
      (where R is the initial lymph capillary radius), due to the predomination of a
      rather rapid convection in this case. This transport time to the lymph nodes may
      be tens of hours (or longer) when y0 is essentially larger and the slow diffusion
      controls the transport rate in a zone not far from the epithelial barrier, where
      convection is weak at large y0. Accounting for transport by diffusion only, which
      is mainly considered in many relevant publications, is not sufficient to explain
      our nanoparticle uptake kinetics because the possibility of fast transport due to
      convection is overlooked. Our systematic investigations have revealed that the
      information about the main transport conditions, namely, y0 and the pore
      broadening up to the dimension of the interstitial transport channels, is
      necessary to create the quantitative model of enhanced transport during
      inflammation with the use of the proposed model as a prerequisite. The modeling
      for convective diffusion of nanoparticles from the epithelial barrier to the
      lymph node has been mainly accomplished here, while the diffusion only scenario
      is accounted for in other studies. This first modeling is a semi-quantitative
      one. A more rigorous mathematical approach is almost impossible at this stage
      because the transport properties of the model are introduced here for the first
      time. These properties include: discovery of foci in the epithelium, formation of
      transport channels, definition of channels interconnecting with foci (effective
      foci and channels), generation of flow in the interstitium toward the initial
      lymph capillaries due to axial flow within afferent lymphatics, deformation of
      this flow due to hydrodynamic impermeability of the squamous layer with the
      formation of the hydrodynamic stagnation zone near the epithelial barrier,
      predomination of slow diffusion transport within the above zone, and
      predomination of fast convection of nanoparticles near the initial lymph
      capillaries. 

PMID- 23859222
TI  - Understanding glycoprotein behaviours using Raman and Raman optical activity
      spectroscopies: characterising the entanglement induced conformational changes in
      oligosaccharide chains of mucin.
AB  - We illustrate the great potential of Raman and ROA spectroscopies for
      investigating the structure and organisation of glycoproteins and the complex
      matrices they can form. In combination these spectroscopic techniques are
      sensitive to changes in conformation revealing details of secondary and tertiary
      structures, probing hydrogen bonding interactions, as well as resolving side
      chain orientation and the absolute configuration of chiral substructures. To
      demonstrate this potential we have characterised the structural changes in a
      complex glycoprotein, mucin. Spectral changes were observed during the
      entanglement transition as the mucin concentration was increased. By applying two
      dimensional correlation analysis (2DCos) to the ROA and Raman concentration
      dependent spectral sets delicate transitions in mucin conformation could also be
      determined. From ~20-40 mg/ml conformational transitions assigned mainly to the
      sugar N-acetyl-d-galactosamine (GalNAc), which is the linking saccharide unit to
      the protein backbone, were monitored. Further changes in local oligosaccharide
      conformation above 40 mg/ml were also monitored, together with other structural
      transitions observed in the protein core, particularly beta-structure formation.
      Consequently, these spectral techniques were shown to monitor the formation of
      transient entanglements formed by brush-brush interactions between
      oligosaccharide combs of mucin molecules identifying changes in both carbohydrate
      and protein moieties. This work clearly shows how these methods can be used to
      elucidate fresh insights into the complex behaviour of these large complex
      molecules.

PMID- 23859223
TI  - Environmental determinants of population divergence in life-history traits for an
      invasive species: climate, seasonality and natural enemies.
AB  - Invasive species cope with novel environments through both phenotypic plasticity
      and evolutionary change. However, the environmental factors that cause
      evolutionary divergence in invasive species are poorly understood. We developed
      predictions for how different life-history traits, and plasticity in those
      traits, may respond to environmental gradients in seasonal temperatures, season
      length and natural enemies. We then tested these predictions in four geographic
      populations of the invasive cabbage white butterfly (Pieris rapae) from North
      America. We examined the influence of two rearing temperatures (20 and 26.7 
      degrees C) on pupal mass, pupal development time, immune function and fecundity.
      As predicted, development time was shorter and immune function was greater in
      populations adapted to longer season length. Also, phenotypic plasticity in
      development time was greater in regions with shorter growing seasons. Populations
      differed significantly in mean and plasticity of body mass and fecundity, but
      these differences were not associated with seasonal temperatures or season
      length. Our study shows that some life-history traits, such as development time
      and immune function, can evolve rapidly in response to latitudinal variation in
      season length and natural enemies, whereas others traits did not. Our results
      also indicate that phenotypic plasticity in development time can also diverge
      rapidly in response to environmental conditions for some traits. 

PMID- 23859224
TI  - New assessment of organic mercury formation in highly polluted sediments in the
      Lenga estuary, Chile.
AB  - Anomalously high levels of mercury in sediment in the Lenga estuary, Chile are
      comparable to the most contaminated sites previously reported elsewhere. Total
      mercury (Hgtotal) concentrations range from 0.5 to 129 mg kg(-1) and organic
      mercury (Hgorg) from 11 to 53 MUg kg(-1). The highest levels are in areas near
      the previous wastewater outfall of a chlo-alkali plant. The results show that the
      proportion of Hgorg/Hgtotal in the sediment varies by more than two orders of
      magnitude (0.02-5.7%) according to the concentration of Hgtotal. No correlation
      between the concentration of Hgorg and Hgtotal was found. The lack of correlation
      does contrast with the findings of other authors in culture media. Our results
      indicate that even at very high concentrations of Hgtotal and organic matter do
      not influence organic mercury formation in estuary sediments. The disparity in
      Hgtotal and Hgorg concentrations also attests to environmental differences in the
      formation.

PMID- 23859225
TI  - Acceleration of peripheral nerve regeneration through asymmetrically porous nerve
      guide conduit applied with biological/physical stimulation.
AB  - Sufficient functional restoration of damaged peripheral nerves is a big clinical
      challenge. In this study, a nerve guide conduit (NGC) with selective permeability
      was prepared by rolling an asymmetrically porous polycaprolactone/Pluronic F127
      membrane fabricated using a novel immersion precipitation method. Dual
      stimulation (nerve growth factor [NGF] as a biological stimulus and low-intensity
      pulse ultrasound [US] as a physical stimulus) was adapted to enhance nerve
      regeneration through an NGC. The animal study revealed that each stimulation (NGF
      or US) has a positive effect to promote the peripheral nerve regeneration through
      the NGC, however, the US-stimulated NGC group allowed more accelerated nerve
      regeneration compared with the NGF-stimulated group. The NGC group that received
      dual stimulation (NGF and US) showed more effective nerve regeneration behavior
      than the groups that received a single stimulation (NGF or US). The
      asymmetrically porous NGC with dual NGF and US stimulation may be a promising
      strategy for the clinical treatment of delayed and insufficient functional
      recovery of a peripheral nerve. 

PMID- 23859226
TI  - Floor of mouth masses in children: proposal of a new algorithm.
AB  - OBJECTIVE: Many surgical techniques have been described to manage floor of mouth
      masses, but few studies have described the approach to these masses in children.
      This case series summarizes a single institution's experience with pediatric
      floor of mouth masses. METHODS: We performed a retrospective chart review of all
      children who presented at our tertiary care facility with FOM masses between 2007
      and 2012. Charts were reviewed for clinical presentation, preoperative,
      intraoperative and postoperative management. RESULTS: Thirteen cases were
      retrieved: 6 dermoid cysts, 4 ranulas, 1 lymphatic malformation, 1 imperforate
      submandibular duct, and 1 enlarged salivary gland. In 10 of 13 patients, clinical
      diagnosis was consistent with postoperative diagnosis. Imaging was consistent
      with postoperative diagnosis in 8 of 9 cases. Ten of 13 masses were managed
      transorally; 7 were excised, 2 were marsupialized and 1 was managed with
      submandibular duct dilation. Three masses with a larger submental component, 2
      dermoids and 1 ranula, were removed transcervically. Most patients undergoing
      transoral excision underwent nasotracheal intubation; patients who underwent
      marsupialization underwent orotracheal intubation. There were no recurrences,
      complications or postoperative infections. An additional surgical procedure was
      necessary in one patient. CONCLUSION: Our cohort displays a common distribution
      of lesion types when compared to the literature. Low recurrence and infection
      rates are observed when oral masses are removed transorally, and masses with a
      larger cervical component are removed transcervically. More complex masses may
      warrant additional surgical procedures.

PMID- 23859227
TI  - Management of a rare case of arytenoid mucosa oedema inducing stridor and cough.
AB  - OBJECTIVE: Current guidelines recommend a multidisciplinary systematic integrated
      approach to patient with chronic cough in which nowadays otolaryngologists play
      an increasingly valuable role as new procedures are used for evaluation and
      treatment. Surgery has been never taken into consideration to treat refractory
      chronic cough. METHOD: We present a rare case of arytenoid mucosa oedema inducing
      stridor and cough, lasting 8 months, that critically affected the quality of life
      of a 15-year-old adolescent arrived to our emergency department with prominent
      arytenoid oedema causing paroxysmal cough and laryngeal stridor and that was
      successfully treated by laryngeal debridement. RESULTS: In this case report we
      observed that prominent swelling of arytenoid mucosa might sustain a vicious
      cycle of cough persistence and that laryngeal surgical debridement might
      interrupt it resolving the particular clinical condition. CONCLUSION: The
      description of this case could be of some help for clinicians to draw new insight
      about diagnosis and therapy of rare selected cases of chronic refractory cough.

PMID- 23859228
TI  - Pedestrian and motorized mobility scooter safety of older people.
AB  - OBJECTIVES: After driving, walking is older adults' second most preferred mode of
      transport and preferred recreational activity. This leads to greater exposure to
      traffic, increasing their risk of pedestrian-vehicle crashes, with older adults
      being more likely to die as a pedestrian compared to when using other modes of
      transport. However, less focus has been placed on this particularly vulnerable
      group. This review summarizes issues associated with older adult pedestrian and
      motorized mobility scooters (MMS) safety and interventions that have been
      conducted. METHODS: A literature search was undertaken from PubMed, MUARC
      publications, the Curtin University Library Catalogue, and Google Scholar.
      Keywords included older pedestrians, older adult road injury, mobility scooter
      injury, and injury prevention. Publications from 2000 and later were used, unless
      an earlier publication had significant relevance and worth. CONCLUSION:
      Maintaining older adults' mobility and independence during a time of decreasing
      physical and mental capacity is a priority. Walking provides a key mode of
      transport that needs to be given higher priority within the road environment by
      policy makers, transport planners, and drivers. Therefore, governments need to
      consider appropriate and comprehensive urban planning and road safety policies
      that accommodate active aging to provide pedestrians and MMS users with
      environments that facilitate active living and safe transport. In addition, there
      is a need for community programs that raise awareness about safe road crossing
      for this growing vulnerable age group.

PMID- 23859230
TI  - Homoserine catabolism by Rhizobium leguminosarum bv. viciae 3841 requires a
      plasmid-borne gene cluster that also affects competitiveness for nodulation.
AB  - Homoserine represents a substantial component of pea root exudate that may be
      important for plant-microbe interactions in the rhizosphere. We identified a gene
      cluster on plasmid pRL8JI that is required for homoserine utilization by
      Rhizobium leguminosarum bv. viciae. The genes are arranged as two divergently
      expressed predicted operons that were induced by L-homoserine, pea root exudate,
      and were expressed on pea roots. A mutation in gene pRL80083 that prevented
      utilization of homoserine as a sole carbon and energy source affected the
      mutant's ability to nodulate peas and lentils competitively. The homoserine gene
      cluster was present in approximately 47% of natural R. leguminosarum isolates (n
      = 59) and was strongly correlated with homoserine utilization. Conjugation of
      pRL8JI to R. leguminosarum 4292 or Agrobacterium tumefaciens UBAPF2 was
      sufficient for homoserine utilization. The presence of L-homoserine increased
      conjugation efficiency of pRL8JI from R. leguminosarum to a pRL8JI-cured
      derivative of R. leguminosarum 1062 and to A. tumefaciens UBAPF2, and induced
      expression of the plasmid transfer gene trbB; however, there was no difference in
      conjugation efficiency or trbB expression with A. tumefaciens UBAPF2pRL8-Gm as
      the donor suggesting that other genes in R. leguminosarum may contribute to
      regulating conjugation of pRL8 in the presence of homoserine.

PMID- 23859231
TI  - Spatio-temporal dynamics in the response of woodland caribou and moose to the
      passage of grey wolf.
AB  - Predators impact prey populations not only by consuming individuals, but also by
      altering their behaviours. These nonlethal effects can influence food web
      properties as much as lethal effects. The mechanisms of nonlethal effects include
      chronic and temporary anti-predator behaviours, the nature of which depends on
      the spatial dynamics of predators and the range over which prey perceive risk.
      The relation between chronic and ephemeral responses to risk determines predator
      prey interactions, with consequences that can ripple across the food web.
      Nonetheless, few studies have quantified the spatio-temporal scales over which
      prey respond to predation threat, and how this response varies with habitat
      features. We evaluated the reaction of radio-collared caribou and moose to the
      passage of radio-collared wolves, by considering changes in movement
      characteristics during winter and summer. We used an optimization algorithm to
      identify the rate at which the impact of prior passage of wolves decreases over
      time and with the predator's distance. The spatial and temporal scales of anti
      predator responses varied with prey species and season. Caribou and moose
      displayed four types of behaviour following the passage of wolves: lack of
      response, increased selection of safe land cover types, decreased selection of
      risky cover types and increased selection of food-rich forest stands. For
      example, moose increased their avoidance of open conifer stands with lichen in
      summer, which are selected by wolves in this season. Also in winter, caribou
      increased their selection of conifer stands with lichen for nearly 10 days
      following a wolf's passage. This stronger selection for food-rich patches could
      indicate that the recent passage of wolves informs caribou on the current
      predator distribution and reveals the rate at which this information become less
      reliable over time. Caribou and moose used anti-predator responses that combine
      both long- and short-term behavioural adjustments. The spatial game between
      wolves and their prey involves complex and nonlinear mechanisms that vary between
      species and seasons. A comprehensive assessment of risk effects on ecosystem
      dynamics thus requires the characterization of chronic and temporary anti
      predator behaviours.

PMID- 23859229
TI  - Water-soluble vitamins in people with low glomerular filtration rate or on
      dialysis: a review.
AB  - People with low glomerular filtration rate and people on dialysis are
      spontaneously at risk for vitamin deficiency because of the potential for
      problems with decreased appetite and decreased sense of smell and taste, leading
      to decreased intake, and because decreased energy or decreased cognitive ability
      results in difficulties in shopping and cooking. Imposed dietary restrictions
      because of their renal dysfunction and because of comorbidities such as
      hypertension and diabetes exacerbate this problem. Finally, particularly for
      water-soluble vitamins, loss may occur into the dialysate. We did not identify
      any randomized trials of administering daily doses close to the recommended daily
      allowances of these vitamins. In people who are eating at all, deficiencies of B5
      and B7 seem unlikely. It is unclear whether supplements of B2 and B3 are
      necessary. Because of dialyzability and documented evidence of insufficiency in
      dialysis patients, B1 supplementation is likely to be helpful. B6, B9, and B12
      are implicated in the hyperhomocysteinemia observed in patients on dialysis.
      These vitamins have been studied in combinations, in high doses, with the hope of
      reducing cardiovascular outcomes. No reductions in patient-important outcomes
      were seen in adequately powered randomized trials. Because of their involvement
      in the homocysteine pathway, however, supplementation with lower doses, close to
      the recommended daily allowances, may be helpful. Vitamin C deficiency is common
      in patients on dialysis who are not taking supplements: low-dose supplements are
      warranted. Vitamins for dialysis patients contain most or all of the B vitamins
      and low-dose vitamin C. We are not aware of any medical reasons to choose one
      over another. 

PMID- 23859232
TI  - A review on leukotrienes and their receptors with reference to asthma.
AB  - OBJECTIVE AND METHODS: Leukotrienes (LTs) including cysteinyl leukotrienes
      (CysLTs) and LTB4 are the most potent inflammatory lipid mediators and play a
      central role in the pathophysiology of asthma and other inflammatory diseases.
      These biological molecules mediate a plethora of contractile and inflammatory
      responses through specific interaction with distinct G protein-coupled receptors
      (GPCRs). The main objective of this review is to present an overview of the
      biological effects of CysLTs and their receptors, along with the current
      knowledge of mechanisms and role of LTs in the pathogenesis of asthma. RESULTS:
      CysLTs including LTC4, LTD4 and LTE4 are ligands for CysLT1 and CysLT2 receptors,
      and LTB4 is the agonist for BLT1 and BLT2 receptors. The role of CysLT1 receptor
      is well established, and most of the pathophysiological effects of CysLTs in
      asthma are mediated by CysLT1 receptor. Several CysLT1 antagonists have been
      developed to date and are currently in clinical practice. Most common among them
      are classical CysLT1 receptor antagonists such as montelukast, zafirlukast,
      pranlukast, pobilukast, iralukast, cinalukast and MK571. The pharmacological role
      of CysLT2 receptor, however, is less defined and there is no specific antagonist
      available so far. The recent demonstration that mice lacking both known CysLT
      receptors exhibit full/augmented response to CysLT points to the existence of
      additional subtypes of CysLT receptors. LTB4, on the other hand, is another
      potent inflammatory leukotriene, which acts as a strong chemoattractant for
      neutrophils, but weaker for eosinophils. LTB4 is known to play an important role
      in the development of airway hyper-responsiveness in severe asthma. However there
      is no LTB4 antagonist available in clinic to date. CONCLUSION: This review gives
      a recent update on the LTs including their biosynthesis, biological effects and
      the role of anti-LTs in the treatment of asthma. It also discusses about the
      possible existence of additional subtypes of CysLT receptors.

PMID- 23859233
TI  - Probing an artificial polypeptide receptor library using a series of novel
      histamine H3 receptor ligands.
AB  - An artificial polypeptide receptor (APR) library was created by using the self
      organization of N-lipidated peptides attached to cellulose via m-aminophenylamino
      1,3,5-triazine. The response of the library was probed using a series of novel H3
      receptor ligands. Since no guidelines on how to design an APRs selective vs
      certain receptor types exist, a diverse set of amino acids (Ala, Trp, Pro, Glu,
      His, Lys and Ser) were used and coupled with one of three gating fatty acids
      (palmitic, ricinoleic or capric). A competitive adsorption-desorption of an
      appropriate reporter dye was used for the indirect visualization of the
      interactions of guests with particular receptors. The resulted library response
      to individual inhibitors was then arranged in a matrix, preprocessed and analyzed
      using the principal component analysis (PCA) and partial least squares (PLS)
      method. The most important conclusion obtained from the PCA analysis is that the
      library differentiates the probed compounds according to the lipophilicity of the
      gating unit. The PC3 with a dominant absolute contribution of the receptors
      containing Glu allowed for the best separation of the ligands with respect to
      their activity. This conclusion is in agreement with the fact that Glu 206 is a
      genuine ligand counterpart in the natural histamine receptor. 

PMID- 23859234
TI  - Comparison of double inversion recovery and conventional magnetic resonance brain
      imaging in patients with multiple sclerosis and relations with disease
      disability.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central
      nervous system, predominantly affecting the white matter, but also the grey
      matter. Aim of this study was to detect MS lesions with double inversion recovery
      (DIR), fluid-attenuated inversion recovery (FLAIR) and T2-weighted magnetic
      resonance (MR) techniques and determine the sensitivity of these techniques, and
      the correlation between the number of lesions and expanded disability state scale
      (EDSS) scores. Thirty-four patients with MS (20 females and 14 males) were
      included in this study. DIR and conventional MR (T2-A, FLAIR) sequences were
      obtained. Lesions were counted and classified as belonging to one of seven
      anatomical regions: cortical, juxtacortical, deep grey matter, deep white matter,
      mixed white matter-grey matter, periventricular white matter and infratentorial.
      The correlation between lesion number and EDSS scores was investigated. DIR
      images showed more intracortical and mixed white matter-grey matter lesions in
      comparison with both FLAIR and T2 sequences (p=0, p=0 respectively). There was a
      significant difference between mean lesion numbers at the juxtacortical region,
      obtained with DIR and T2-weighted images (p = 0.002). The total number of lesions
      obtained with all methods was similar. DIR brain imaging had the highest
      sensitivity in the detection of cortical and mixed white matter - grey matter
      lesions, compared with FLAIR and T2 sequences. In addition, the lesions obtained
      with DIR images were more easily visualized. 

PMID- 23859235
TI  - Multiple sclerosis: identification of temporal changes in brain lesions with
      computer-assisted detection software.
AB  - Multiple sclerosis (MS) is a chronic disease with a progressing and evolving
      course. Serial imaging with MRI is the mainstay in monitoring and managing MS
      patients. In this work we demonstrate the performance of a locally developed
      computer-assisted detection (CAD) software used to track temporal changes in
      brain MS lesions. CAD tracks changes in T2-bright MS lesions between two time
      points on a 3D high-resolution isotropic FLAIR MR sequence of the brain acquired
      at 3 Tesla. The program consists of an image-processing pipeline, and displays
      scrollable difference maps used as an aid to the neuroradiologist for assessing
      lesional change. To assess the value of the software we have compared diagnostic
      accuracy and duration of interpretation of the CAD-assisted and routine clinical
      interpretations in 98 randomly chosen, paired MR examinations from 88 patients
      (68 women, 20 men, mean age 43.5, age range 21-75) with a diagnosis of definite
      MS. The ground truth was determined by a three-expert panel. In case-wise
      analysis, CAD interpretation showed higher sensitivity than a clinical report
      (87% vs 77%, respectively). Lesion-wise analysis demonstrated improved
      sensitivity of CAD over a routine clinical interpretation of 40%-48%. Mean
      software-assisted interpretation time was 2.7 min. Our study demonstrates the
      potential of including CAD software in the workflow of neuroradiology practice
      for the detection of MS lesional change. Automated quantification of temporal
      change in MS lesion load may also be used in clinical research, e.g., in drug
      trials. 

PMID- 23859236
TI  - Progressive multifocal leukoencephalopathy presenting as IRIS in an AIDS patient.
      A case report and literature review.
AB  - Progressive multifocal leukoencephalopathy causes an infection of the central
      nervous system by JC virus (JCV), a polyomavirus that destroys oligodendrocytes
      and their myelin processes. Here, we describe a patient with AIDS who developed a
      progressive multifocal leucoencephalopathy with the clinical and neuroimaging
      characteristics of the immune inflammatory reconstitution syndrome. Unlike other
      opportunistic infections, this disease can present when CD4 T cell counts are
      higher than those associated with AIDS and also when patients are receiving
      combined antiretroviral therapy. Clinical suspicion of this form of the disease
      is based on clinical examination that shows focal neurological deficits
      associated with magnetic resonance images findings. The histopathological
      examination of brain biopsy smears and the identification of JCV in cerebrospinal
      fluid or brain tissue are definitive for the diagnosis. 

PMID- 23859237
TI  - Brain MRI findings as an important diagnostic clue in glutaric aciduria type 1.
AB  - Glutaric aciduria type 1 is an autosomal recessive disorder caused by deficiency
      of glutaryl-coenzyme A dehydrogenase, with accumulation of glutaric acid, 3
      hydroxyglutaric acid and glutaconic acid. Increased blood glutarylcarnitine
      levels are the basis for identification of affected infants by newborn screening.
      Despite the highly variability, this disease usually presents with an acute
      encephalitis-like encephalopathy in infancy or childhood after a period of normal
      development. The characteristic neurological sequel is a complex movement
      disorder due to acute bilateral striatal injury. Frequently, the only abnormality
      preceding the first episode is a progressive macrocephaly. Although neuroimaging
      findings are quite variable, the widening of the Sylvian fissures combined with
      abnormalities of the basal ganglia in a child with macrocephaly should raise the
      suspicion of this diagnosis. We describe two patients in whom macrocephaly was
      the only presenting symptom and whose diagnosis was suggested by the brain MRI
      findings. Our purpose is to illustrate the clinical value of neuroimaging in the
      diagnosis of glutaric aciduria type 1 even before the onset of neurologic
      symptoms, which is particularly important if newborn screening is not available. 

PMID- 23859238
TI  - Expansion diverticulum of the suprapineal recess causing cerebellar ataxia. A
      case report.
AB  - As a result of long-standing cerebrospinal fluid (CSF) pulsation against the
      thinnest segments of the ventricular walls, focal enlargement of the ventricular
      system (diverticulum) may occur, mainly at the medial wall of the trigone of the
      lateral ventricles (atrial diverticula) or at the posterior wall of the third
      ventricle (expansion of the suprapineal recess). In the latter case, ocular signs
      are the most common symptoms, due to the severe deformation of the periaqueductal
      region. We describe a case of non-communicating hydrocephalus in a 36-year-old
      woman who presented a three-year history of cerebellar ataxia. Preoperative brain
      magnetic resonance (MR) scan showed marked supratentorial hydrocephalus with an
      apparently patent aqueduct of Sylvius, and an enlarged suprapineal recess causing
      cerebellar and tentorial dislocation. The patient was successfully treated by
      endoscopic third ventriculostomy and monitored by MR scans with phase-contrast
      sequences for assessment of CSF flow. Cerebellar ataxia is a very rare
      symptomatic onset for a suprapineal recess expansion diverticulum, which may
      cause obstructive hydrocephalus that can be effectively treated by endoscopic
      third ventriculostomy. 

PMID- 23859239
TI  - Nosocomial Herpes Encephalitis: rare but treatable with early MR diagnosis.
AB  - Nosocomial/hospital acquired herpes encephalitis is rare and is usually
      undiagnosed in its early phase because of the non-specific clinical picture and
      low level of clinical and neuroimaging suspicion. There is a paucity of data in
      radiology literature for this entity, specifically in the settings of surgery and
      trauma. We describe two cases of nosocomial herpes simplex encephalitis to
      demonstrate the imaging clues that might lead to an early diagnosis of this
      disease. 

PMID- 23859240
TI  - A Bayesian diagnostic system to differentiate glioblastomas from solitary brain
      metastases.
AB  - This paper aimed to construct a Bayesian network-based decision support system to
      differentiate glioblastomas from solitary metastases, based on multimodality MR
      examination. We enrolled 51 patients with solitary brain tumors (26 with
      glioblastomas and 25 with solitary brain metastases). These patients underwent
      contrast-enhanced T1-weighted magnetic resonance (MR) examination, diffusion
      tensor imaging (DTI), dynamic susceptibility contrast (DSC) MRI, and fluid
      attenuated inversion recovery (FLAIR). We generated a set of MR biomarkers,
      including relative cerebral blood volume in the enhancing region, and fractional
      anisotropy measured in the immediate peritumoral area. We then generated a
      Bayesian network model to represent associations among these imaging-derived
      predictors, and the group membership variable, (glioblastoma or solitary
      metastasis). This Bayesian network can be used to classify new patients' tumors
      based on their MR appearance. The Bayesian network model accurately
      differentiated glioblastomas from solitary metastases. Prediction accuracy was
      0.94 (sensitivity = 0.96, specificity = 0.92) based on leave-one-out cross
      validation. The area under the receiver operating characteristic curve was 0.90.
      A Bayesian network-based decision support system accurately differentiates
      glioblastomas from solitary metastases, based on MR-derived biomarkers. 

PMID- 23859241
TI  - Brain microbleeds: distribution and influence on hematoma and perihematomal edema
      in patients with primary intracerebral hemorrhage.
AB  - Brain microbleed is a marker of small vessel microhemorrhagic or microaneurysmal
      lesions, which may induce intracerebral hemorrhage (ICH). This study to
      prospectively evaluated the association between microbleeds, hematoma and
      perihematomal edema volume, and various clinical data, as well as patient
      outcome. Thirty-one patients with ICH and 31 healthy age-matched subjects were
      enrolled in our study. They were divided into two groups according to the
      presence or absence of microbleeds detected by MRI. Serial clinical and
      laboratory data were recorded. Modified Rankin Scale and Barthel Index were
      estimated three months after hemorrhage. The major location of microbleeds among
      patients with ICH was the basal ganglia. The volume of perihematomal edema was
      correlated with the initial hematoma volume on the first, fifth and seventh days
      after hemorrhage in patients with microbleeds. For patients without microbleeds,
      this correlation was also significant on the seventh day. Cerebral microbleeds in
      patients with ICH, especially in the basal ganglia region, represent micro
      angiopathy, and are associated with leakage of blood and formation of
      perihemorrhage edema. Brain microbleeds found in patients with ICH warrant
      further investigation for evaluation of stroke risk. 

PMID- 23859242
TI  - Sickle cell anemia: reference values of cerebral blood flow determined by
      continuous arterial spin labeling MRI.
AB  - Sickle cell anemia (SCA) is a chronic illness associated with progressive
      deterioration in patients' quality of life. The major complications of SCA are
      cerebrovascular accidents (CVA) such as asymptomatic cerebral infarct or overt
      stroke. The risk of CVA may be related to chronic disturbances in cerebral blood
      flow (CBF), but the thresholds of "normal" steady-state CBF are not well
      established. The reference tolerance limits of CBF can be useful to estimate the
      risk of CVA in asymptomatic children with SCA, who are negative for hyperemia or
      evidence of arterial narrowing. Continuous arterial spin labeling (CASL) MR
      perfusion allows for non-invasive quantification of global and regional CBF. To
      establish such reference tolerance limits we performed CASL MR examinations on a
      3-Tesla MR scanner in a carefully selected cohort of 42 children with SCA (mean
      age, 8.1+/-3.3 years; range limits, 2.3-14.4 years; 24 females), who were not on
      chronic transfusion therapy, had no history of overt stroke or transient ischemic
      attack, were free of signs and symptoms of focal vascular territory ischemic
      brain injury, did not have intracranial arterial narrowing on MR angiography and
      were at low risk for stroke as determined by transcranial Doppler
      ultrasonography. 

PMID- 23859243
TI  - Developmental venous anomaly responsible for hemifacial spasm.
AB  - Hemifacial spasm (HFS) is a facial movement disorder characterized by
      involuntary, unilateral and intermittent contractions of the facial muscles. It
      is one of the syndromes related to neurovascular conflict, first described by
      Jannetta et al. in 1979. Typically, HFS is due to pulsatile compression by the
      anterior inferior cerebellar artery. We describe a rare case of left
      developmental venous anomaly in a 59-year-old man referred to us with a six-month
      history of left-sided HFS. We performed an MR study of the brain and
      cerebellopontine angles, which demonstrated a compression of the ipsilateral
      facial nerve by the developmental venous anomaly. 

PMID- 23859244
TI  - Intracranial hypertension due to meningioma of the unique transverse sinus.
AB  - We describe a 28-year-old woman with intracranial hypertension due to a
      meningioma invading the unique transverse sinus (with absent contralateral
      sinus). Clinical remission and normalization of orbital echography were obtained
      by resection of the intradural tumor and peeling of the dural attachment. In such
      cases, resection and reconstruction of the involved sinus segment is at high risk
      of venous infarction. Endovascular stenting of the obstructed sinus is a valid
      alternative when the stenosis is not remarkable. Single tumor removal may lead to
      partial sinus decompression and increased venous flow, resulting in long-term
      clinical remission. 

PMID- 23859245
TI  - Vacuum epidural cyst with acute neurological presentation. A case report.
AB  - The widespread use of MRI in the assessment of low back pain has led to increased
      detection of degenerative cysts of the spine, which was essentially a surgical
      diagnosis earlier. The awareness of degenerative cysts, the significance of their
      role in the etiology of radicular and back pain and their effective management is
      evolving. We describe a case of bilateral, gas-filled lumbar facet synovial/
      ganglion cysts causing focal arachnoid inflammation and lateral lumbar canal
      stenosis. 

PMID- 23859246
TI  - CSF pressure and velocity in obstructions of the subarachnoid spaces.
AB  - According to some theories, obstruction of CSF flow produces a pressure drop in
      the subarachnoid space in accordance with the Bernoulli theorem that explains the
      development of syringomyelia below the obstruction. However, Bernoulli's
      principle applies to inviscid stationary flow unlike CSF flow. Therefore, we
      performed a series of computational experiments to investigate the relationship
      between pressure drop, flow velocities, and obstructions under physiologic
      conditions. We created geometric models with dimensions approximating the spinal
      subarachnoid space with varying degrees of obstruction. Pressures and velocities
      for constant and oscillatory flow of a viscid fluid were calculated with the
      Navier-Stokes equations. Pressure and velocity along the length of the models
      were also calculated by the Bernoulli equation and compared with the results from
      the Navier-Stokes equations. In the models, fluid velocities and pressure
      gradients were approximately inversely proportional to the percentage of the
      channel that remained open. Pressure gradients increased minimally with 35%
      obstruction and with factors 1.4, 2.2 and 5.0 respectively with 60, 75 and 85%
      obstruction. Bernoulli's law underestimated pressure changes by at least a factor
      2 and predicted a pressure increase downstream of the obstruction, which does not
      occur. For oscillatory flow the phase difference between pressure maxima and
      velocity maxima changed with the degree of obstruction. Inertia and viscosity
      which are not factored into the Bernoulli equation affect CSF flow. Obstruction
      of CSF flow in the cervical spinal canal increases pressure gradients and
      velocities and decreases the phase lag between pressure and velocity. 

PMID- 23859247
TI  - Paravertebral high cervical chordoma. A case report.
AB  - Spinal chordomas are more often located on the midline and are associated with
      marked destruction of the vertebral bodies. We report a rare case of large
      cervical (C2-C3) right lateral paravertebral chordoma extending into the spinal
      canal through a very enlarged intervertebral foramen. The tumor was initially
      diagnosed as a mucous adenocarcinoma on a percutaneous needle biopsy. However,
      the neuroradiological features, including the well-defined tumor margins, the
      regular and sclerosing lytic bone changes with regular enlargement of the
      intervertebral C2-C3 foramen, were in favor of a more slowly growing lesion, such
      as schwannoma or neurofibroma. At surgery a well-demarcated capsulated tumor
      involving the nerve root was partially resected. Histology was in favor of a low
      grade chordoma (Ki-67/MIB-1<1%). Postoperative proton beam therapy was also
      performed. The differential neuroradiological diagnosis is discussed. 

PMID- 23859248
TI  - Does chronic pre-operative pain predict severe post-operative pain after
      thoracotomy? A prospective longitudinal study.
AB  - BACKGROUND: Despite advances in pain research, many patients still experience
      moderate to severe post-operative pain that needs to be alleviated. The primary
      aim of this study was to identify predictive factors for severe post-operative
      pain after thoracotomy. Secondary, we investigated the levels of post-operative
      pain in this group of patients. METHODS: A prospective longitudinal study with
      144 patients scheduled for thoracotomy was conducted between December 2007 and
      August 2010. All patients were given a questionnaire consisting of three sections
      (Brief Pain Inventory, Life Orientation Test-revised and Hospital Anxiety and
      Depression Scale) the day before surgery. Only those patients with pre-existing
      chronic pain were asked to complete all three sections. Post-operative pain
      scores were recorded three times a day for 6 days using the Numeric Rating Scale,
      and all analgesic consumption was recorded daily. RESULTS: Fifty-four patients
      reported pre-existing pain before surgery, most commonly from the neck,
      shoulders, lower back, hips or knees. For the first 3 days after surgery, the
      pain scores for those who had pre-existing chronic pain and those who did not,
      where almost similar with no statistically significant difference. The total
      amount of the epidural analgesia-mixture used where also almost similar for both
      groups with no statistically significant difference. CONCLUSION: In contrast to
      previous studies, which have reported pre-operative chronic pain to be a strong
      predictor of moderate to severe post-operative pain, we have in our study not
      been able to replicate these findings.

PMID- 23859249
TI  - trans-Resveratrol in Gnetum gnemon protects against oxidative-stress-induced
      endothelial senescence.
AB  - Gnetum gnemon is an arboreal dioecious plant that is cultivated in Indonesia. The
      seeds of this species mainly contain dimeric stilbenoid compounds [gnetin C (1),
      gnemonoside A (2), and gnemonoside D (3)] along with trans-resveratrol (4). trans
      Resveratrol has been reported to have antiaging, anticancer, and antidiabetic
      effects, as well as being a calorie restriction mimetic. SIRT1 exerts a
      protective effect against vascular senescence. In this study, the effects of
      these four main stilbenoid derivatives of a G. gnemon seed endosperm ethanolic
      extract on endothelial senescence were investigated. In streptozotocin-induced
      diabetic mice, administration of the G. gnemon ethanolic extract increased SIRT1
      and decreased endothelial senescence. The concentration of 1 in blood plasma was
      6-fold higher than 4 in these mice. Next, the in vitro effects of the four main
      stilbenoid derivatives of G. gnemon seeds were investigated. Senescent human
      umbilical vein endothelial cells were induced by hydrogen peroxide. Endothelial
      senescence was inhibited by 4, which increased the expression of endothelial
      nitric oxide synthase and SIRT1, whereas 1-3 had no effect. These results
      indicated that the ethanolic extract of G. gnemon seeds inhibits endothelial
      senescence, suggesting that 4 plays a critical role in the prevention of
      endothelial senescence. 

PMID- 23859250
TI  - Factors influencing patient decisions to initiate and discontinue subcutaneous
      testosterone pellets (Testopel) for treatment of hypogonadism.
AB  - INTRODUCTION: A variety of modalities for testosterone replacement therapy (TRT)
      are available, including topical gels, injections, and Testopel subcutaneous
      testosterone pellets (STP). STP are becoming more commonly utilized in the United
      States; however, patient preferences, expectations, and usage patterns regarding
      this therapy remain poorly characterized. AIM: To identify factors influencing
      patients' decisions to initiate or discontinue STP. METHODS: A total of 175 men
      from an academic urology clinic who were currently using or who had previously
      used STP for hypogonadism received a 32-item electronic survey. MAIN OUTCOME
      MEASURES: Assessment of the impact of convenience, efficacy, side effects, cost,
      and symptom relief on initiation and discontinuation of STP. RESULTS: One hundred
      and thirteen men (64.6% response rate) of mean age 51.4 years who previously
      underwent a mean of 2.8 STP implant procedures completed the survey. Fifty-nine
      (52.2%) and 40 (35.4%) men had switched to STP from topical gel and injection
      therapy, respectively, whereas 14 (12.4%) men initially started TRT with STP.
      Convenience (68.8%) was the most important factor in patients' decision to start
      STP, while cost of the previous form of TRT (14.7%) was least important. At the
      time of the survey, 32 men (28.3%) had discontinued STP therapy. Cost of therapy
      (50%) was the primary factor in discontinuing STP. There was no difference in
      serum testosterone levels between men who continued STP and those who
      discontinued therapy (642.8 vs. 629.0 ng/dL, P = 0.83). Overall, 68.1% of
      patients continued STP therapy at the time of survey completion. CONCLUSIONS:
      Convenience is the most important factor in a patient's decision to initiate STP;
      however, physician recommendation also plays a substantial role. Cost was the
      primary reason for discontinuation. Upon survey completion, greater than two
      thirds of respondents elected to continue STP therapy. STP are a viable treatment
      option for hypogonadal men seeking a convenient and efficacious alternative
      modality of TRT.

PMID- 23859251
TI  - Dose escalation using helical tomotherapy improves local control in spine
      metastases from primary hepatic malignancies.
AB  - BACKGROUND & AIMS: This study was designed to reveal the prognostic significance
      of dose-escalated radiotherapy with tomotherapy in local control for spine
      metastases of primary hepatic tumours. METHODS: From April 2006 to May 2012, 23
      hepatocellular carcinoma patients and 7 intrahepatic cholangiocellular carcinoma
      patients (total 30 patients, 42 spinal lesions) were treated for metastatic spine
      lesions with helical tomotherapy (HT). The gross tumour volume (GTV) was defined
      as a tumour evident from computed tomography and magnetic resonance imaging.
      Median values were as follows: GTV total dose of 48 Gy (range 21-51), fraction
      size of 6 Gy (range 3-8) and eight fractions (range 3-17). Pain response was
      checked according to visual analogue scale (from 0 to 10). RESULTS: The median
      follow-up was 5.6 months. Six events of local failure occurred, including five
      lesions in which spinal canals were involved at radiotherapy. Local control rate
      at 3 months was 86.6%. Biological equivalent dose (BED) was correlated with local
      control (AUC = 0.833). Higher BED (>56.0 Gy10 ) was associated with increased
      local control (P = 0.004). The median time to local progression in patients
      receiving <=56.0 Gy10 and >56.0 Gy10 were 3 and 20.8 months respectively. Dose
      escalation (BED > 56.0 Gy10 ) was also associated with improved progression-free
      survival (median 14.7 vs. 2.8 months, P = 0.010). Pain reduction was observed in
      90.9% (20/22) of patients with painful bone metastases. CONCLUSIONS: Dose
      escalated radiotherapy (BED > 56.0 Gy10 ) using HT improved local control in
      spinal metastases of hepatic malignancies.

PMID- 23859252
TI  - Immunotoxicity and genotoxicity testing of PLGA-PEO nanoparticles in human blood
      cell model.
AB  - A human blood cell model for immunotoxicity and genotoxicity testing was used to
      measure the response to polylactic-co-glycolic acid (PLGA-PEO) nanoparticle (NP)
      (0.12, 3, 15 and 75 MUg/cm(2) exposure in fresh peripheral whole blood
      cultures/isolated peripheral blood mononuclear cell cultures from human
      volunteers (n = 9-13). PLGA-PEO NPs were not toxic up to dose 3 MUg/cm(2); dose
      of 75 MUg/cm(2) displays significant decrease in [(3)H]-thymidine incorporation
      into DNA of proliferating cells after 4 h (70% of control) and 48 h (84%)
      exposure to NPs. In non-cytotoxic concentrations, in vitro assessment of the
      immunotoxic effects displayed moderate but significant suppression of
      proliferative activity of T-lymphocytes and T-dependent B-cell response in
      cultures stimulated with PWM > CON A, and no changes in PHA cultures. Decrease in
      proliferative function was the most significant in T-cells stimulated with CD3
      antigen (up to 84%). Cytotoxicity of natural killer cells was suppressed
      moderately (92%) but significantly in middle-dosed cultures (4 h exposure). On
      the other hand, in low PLGA-PEO NPs dosed cultures, significant stimulation of
      phagocytic activity of granulocytes (119%) > monocytes (117%) and respiratory
      burst of phagocytes (122%) was recorded. Genotoxicity assessment revealed no
      increase in the number of micronucleated binucleated cells and no induction of
      SBs or oxidised DNA bases in PLGA-PEO-treated cells. To conclude on immuno- and
      genotoxicity of PLGA-PEO NPs, more experiments with various particle size, charge
      and composition need to be done.

PMID- 23859253
TI  - Density-dependent life history and the dynamics of small populations.
AB  - 1. Small population dynamics depend importantly on the strength and shape of
      density dependence. Unfortunately, the lack of reliable life-history data often
      prevents to make accurate demographic predictions for populations regulated by
      density dependence. 2. We created a gradient from low to high densities in small
      experimental populations of common lizards (Zootoca vivipara) and investigated
      the shape and strength of the density dependence of life-history traits during a
      yearly cycle. We then analysed stochastic population dynamics using one-sex and
      two-sex age-structured matrix models. 3. Body growth and reproductive
      performances decreased with density, yearling and adult survival and body size at
      birth were density-independent, and juvenile survival increased with density. The
      density dependence of reproduction was partly explained by positive effects of
      body size on age at first reproduction and clutch size. 4. Parturition date
      decreased with density in sparse populations and then increased, providing one of
      the first empirical evidence of a component Allee effect in the phenology of
      reproduction. 5. Population growth rate (lambda) was most affected by variations
      in juvenile and yearling survival. However, density at equilibrium was most
      affected by juvenile access to reproduction and yearling clutch size. 6.
      Stochastic simulations revealed that negative density dependence buffers the
      effects of initial density on extinction probability, has positive effects on the
      persistence of sparse populations and interacts with sex ratio fluctuations to
      shape extinction dynamics. 7. This study demonstrates that negative density
      dependence modifies the dynamics of small populations and should be investigated
      together with Allee effects to predict extinction risks.

PMID- 23859254
TI  - The SpoIIQ landmark protein has different requirements for septal localization
      and immobilization.
AB  - Bacillus subtilis sporulation depends on the forespore membrane protein SpoIIQ,
      which interacts with the mother cell protein SpoIIIAH at the septum to localize
      other sporulation proteins. It has remained unclear how SpoIIQ localizes. We
      demonstrate that localization of SpoIIQ is achieved by two pathways: SpoIIIAH and
      the SpoIID, SpoIIM, SpoIIP engulfment proteins. SpoIIQ shows diffuse localization
      only in a mutant lacking both pathways. Super-resolution imaging shows that in
      the absence of SpoIIIAH, SpoIIQ forms fewer, slightly larger foci than in wild
      type. Surprisingly, photobleaching experiments demonstrate that, although SpoIIQ
      localizes without SpoIIIAH, it is no longer immobilized, and is therefore able to
      exchange subunits within a localized pool. SpoIIQ mobility is further increased
      by the additional absence of the engulfment proteins. However an enzymatically
      inactive SpoIID protein immobilizes SpoIIQ even in the absence of SpoIIIAH,
      indicating that complete septal thinning is not required for SpoIIQ localization.
      This suggests that SpoIIQ interacts with both SpoIIIAH and the engulfment
      proteins or their peptidoglycan cleavage products. They further demonstrate that
      apparently normal localization of a protein without a binding partner can mask
      dramatic alterations in protein mobility. We speculate that SpoIIQ assembles foci
      along the path defined by engulfment proteins degrading peptidoglycan. 

PMID- 23859255
TI  - Sexual functioning is impaired in adults with congenital heart disease.
AB  - BACKGROUND: To investigate the overall sexual functioning and disease specific
      sexual problems in congenital heart disease (ConHD) patients, for both genders
      and different cardiac diagnostic groups, and compare these with Dutch normative
      data. Also disease specific sexual problems were investigated. METHODS: From a
      longitudinal cohort of patients, operated for ConHD between 1968 and 1980, 254
      patients (median age: 40, 53.4% male) were included in this study: atrial septal
      defect (n = 72), ventricular septal defect (n = 71), pulmonary stenosis (n = 30),
      tetralogy of Fallot (n = 53) and transposition of the great arteries (n = 28).
      Patients completed internationally validated, generic questionnaires and also
      disease specific instruments on sexual functioning. RESULTS: Patients showed a
      delay in starting sexual activities compared with peers. Females with ConHD
      scored significantly worse compared with normative data on all scales of sexual
      functioning, indicating a broad range of sexual problems and 15% showed clinical
      levels of sexual dysfunction. Of the males, 14% suffered from erectile
      dysfunction. Males with ConHD scored worse on erectile function, orgasmic
      function and satisfaction regarding their sexual life compared with normative
      data. No differences were found between the different cardiac diagnoses. The
      majority of patients reported disease specific worries and fears about the use of
      contraceptives, heredity, pregnancy and delivery. Patients indicated to have been
      suboptimally informed about sexuality in early adolescence. CONCLUSIONS: This
      study shows that sexual functioning is impaired in adults with ConHD. Providing
      information to patients about sexuality, pregnancy, delivery and heredity should
      be improved, and given at young age.

PMID- 23859256
TI  - Non-exercise activity thermogenesis is associated with markers for diabetic
      microangiopathy in Japanese female patients with type 2 diabetes.

PMID- 23859257
TI  - Restoring the salivary cortisol awakening response through nasal continuous
      positive airway pressure therapy in obstructive sleep apnea.
AB  - Partial and largely conflicting data are currently available on the interplay
      between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis
      (HPA) activity in adult obese men. This study was performed to evaluate the daily
      trajectories of salivary cortisol, specifically with respect to the salivary
      cortisol awakening response (CAR), a common method used to assess HPA axis
      activity. The main findings of this study were that adult male obese subjects who
      were newly diagnosed with severe OSA showed the following: (1) a flattening of
      the CAR; (2) levels of cortisol at awakening that were lower than those of the
      controls; and (3) maintenance of the physiological circadian activity of the HPA
      axis, with the highest hormone concentrations produced in the morning and the
      lowest in the evening. This study was also designed to investigate the effects of
      3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP
      use resulted in a significant recovery of the sleep patterns disrupted by OSA;
      moreover, mild neuropsychological signs of depression and anxiety in severe OSA
      patients were concomitantly progressively improved by CPAP treatment.
      Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the
      presence of CAR and was able to significantly reduce the difference in the
      morning cortisol levels between the OSA and control groups. In conclusion, we
      report here that compared with obese nonapneic matched controls, OSA patients
      present a dysregulation of HPA axis activity, as shown by the flattening of the
      diurnal pattern of cortisol production in response to repeated challenge due to
      hypoxia and sleep fragmentation. This dysregulation was especially detectable in
      the first hour after awakening and restored after 3 and 6 mos of treatment with
      CPAP. 

PMID- 23859258
TI  - Effect of the addition of organic acids in drinking water or feed during part of
      the finishing period on the prevalence of Salmonella in finishing pigs.
AB  - Pork is a major cause of foodborne salmonellosis. Consequently, effective
      measures that could reduce the prevalence of Salmonella at the farm are of
      interest. In the present study, three field trials were performed to evaluate the
      effect of strategic administration of organic acids, at concentrations estimated
      by economic criteria, on the Salmonella prevalence in finishing pigs. Pigs
      received either a mixture of acids (lactic, formic, propionic, and acetic) added
      to their drinking water at a concentration of 0.035% (trial A), or a basal diet
      containing 0.5% potassium-diformate, KH(COOH)2, (trials B and C), during the last
      6-7 weeks of the finishing period. Fecal Salmonella shedding and seroprevalence
      were monitored in the animals at four time points during the study. Mesenteric
      lymph nodes and cecal contents were collected from a subset of animals at the
      slaughterhouse and cultured for Salmonella. At the end of the finishing period in
      all three trials, the percentage of seropositive pigs was higher in the control
      group than in the experimental group, regardless of which cutoff value was used
      in the enzyme-linked immunosorbent assay (ELISA) assay. The frequency of fecal
      shedding was lower also in the treated pig groups from the trials A and B at the
      end of the finishing period. The results from the samples collected at the
      slaughterhouse did not yield differences between groups in trials A and B.
      However, Salmonella isolation was less frequent in the mesenteric lymph nodes
      from the experimental pigs in trial C. The seroprevalence reductions, together
      with some promising results in the reduction of shedding, support the idea that
      this intervention is a useful strategy to reduce Salmonella prevalence at the
      farm.

PMID- 23859259
TI  - Use of multiple-locus variable-number tandem repeat analysis to evaluate
      Escherichia coli O157 subtype distribution and transmission dynamics following
      natural exposure on a closed beef feedlot facility.
AB  - To better understand the epizootiology of Escherichia coli O157:H7 among cattle,
      all E. coli O157 isolates recovered on a research feedlot during a single feeding
      period were characterized by multiple-locus variable-number tandem repeat
      analysis (MLVA). Three distinct MLVA subtypes (A, B, C), accounting for 24%, 15%,
      and 64% of total isolates, respectively, were identified. Subtypes A and B were
      isolated at the initiation of sampling, but their prevalence waned and subtype C,
      first isolated on the third sampling date, became the predominant subtype on the
      feedlot. Supershedding events, however, occurred with equal frequency for all
      three MLVA-types. Using a multilevel logistic regression model, we investigated
      whether the odds of shedding subtype C relative to subtypes A or B were
      associated with time, diet, or the presence of a penmate shedding high numbers of
      subtype C. Only time and exposure to an animal shedding MLVA-type C at 103 colony
      forming units or greater in the pen at the time of sampling were significantly
      associated with increased shedding of subtype C. High-level shedding of those E.
      coli O157 subtypes better suited for survival in the environment and/or in the
      host appear to play a significant role in the development of predominant E. coli
      O157 subtypes. Supershedding events alone are neither required nor sufficient to
      drive the epidemiology of specific E. coli O157 subtypes. Additional factors are
      necessary to direct successful on-farm transmission of E. coli O157.

PMID- 23859260
TI  - COX-2 inhibitory activity of homoisoflavanones and xanthones from the bulbs of
      the Southern African Ledebouria socialis and Ledebouria ovatifolia
      (Hyacinthaceae: Hyacinthoideae).
AB  - The bulbs of Ledebouria socialis (Hyacinthaceae) yielded the benzocyclobutene
      homoisoflavonoid, (R)-2',5-dihydroxy-3',4',7-trimethoxyspiro{2H-1-benzopyran-3
      (4H)-9-bicyclo[4.2.0]octa[1,3,5]triene}-4-one, socialinone (1). Ledebouria
      ovatifolia yielded (2epsilon,3R)-2,5-dihydroxy-7-methoxyspiro[2H-1-benzopyran
      3(4H), 5'(6'H)-cyclobuta[f][1,3]benzodioxol]-4-one (2) and the homoisoflavanone,
      (E)-3-(3',4'-dihydroxybenzylidene)-5,7-dihydroxychroman-4-one, ovatifolionone
      (5), the dihydrochalcone, 4,4'-dihydroxy-2',6'-dimethoxydihydrochalcone (3), and
      xanthone, 1,6-dihydroxy-2,3,5-trimethoxy-8-methyl-9H-xanthen-9-one (4) along with
      21 known compounds. Structures were determined using spectroscopic techniques.
      The anti-inflammatory activities of the homoisoflavonoids and xanthones isolated
      were evaluated against cyclooxygenase-1 and -2 isoenzymes. (R)-3-(3',4'
      Dihydroxybenzyl)-7-hydroxy-5-methoxychroman-4-one (7), (E)-3-(3',4'
      dihydroxybenzylidene)-7-hydroxy-5-methoxychroman-4-one (10), 1,3,6-trihydroxy-2
      methoxy-8-methylxanthen-9-one (6) and ovatifolionone acetate (5Ac) exhibited
      significant activity against cyclooxygenase-2 at <10MUM. 

PMID- 23859261
TI  - Bioactive steroidal saponins from Agave offoyana flowers.
AB  - Bioguided studies of flowers of Agave offoyana allowed the isolation of five
      steroidal saponins never described previously, Magueyosides A-E (1-5), along with
      six known steroidal saponins (6-11). The structures of compounds were determined
      as (25R)-spirost-5-en-2alpha,3beta-diol-12-one 3-O-{beta-d-xylopyranosyl-(1->3)-O
      beta-d-glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1->3)]-O-beta-d
      glucopyranosyl-(1->4)-O-beta-d-galactopyranoside} (1), (25R)-spirost-5-en
      2alpha,3beta-diol-12-one 3-O-{beta-d-glucopyranosyl-(1->2)-O-[beta-d
      xylopyranosyl-(1->3)]-O-beta-d-glucopyranosyl-(1->4)-O-beta-d-galactopyranoside}
      (2), (25R)-spirost-5-en-2alpha,3beta,12beta-triol 3-O-{beta-d-glucopyranosyl-(1
      >2)-O-[beta-d-xylopyranosyl-(1->3)]-O-beta-d-glucopyranosyl-(1->4)-O-beta-d
      galactopyranoside} (3), (25R)-5alpha-spirostan-2alpha,3beta-diol-12-one 3-O-{beta
      d-xylopyranosyl-(1->3)-O-beta-d-glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1
      >3)]-O-beta-d-glucopyranosyl-(1->4)-O-beta-d-galactopyranoside} (4), and (25R)
      5alpha-spirostan-2alpha,3beta-diol-9(11)-en-12-one 3-O-{beta-d-xylopyranosyl-(1
      >3)-O-beta-d-glucopyranosyl-(1->2)-O-[beta-d-xylopyranosyl-(1->3)]-O-beta-d
      glucopyranosyl-(1->4)-O-beta-d-galactopyranoside} (5), by comprehensive
      spectroscopic analysis, including one- and two-dimensional NMR techniques, mass
      spectrometry and chemical methods. The bioactivities of the isolated compounds on
      the standard target species Lactuca sativa were evaluated. A dose-dependent
      phytotoxicity and low dose stimulation were observed. 

PMID- 23859262
TI  - Plant-derived juvenile hormone III analogues and other sesquiterpenes from the
      stem bark of Cananga latifolia.
AB  - Juvenile hormone III (JH III) is a larval metamorphosis-regulating hormone
      present in most insect species. JH III was first isolated from the plant, Cyperus
      iria L., but the presence of JH III has not been reported in other plant species.
      In the present study, proof of the existence of JH III and its analogues from
      Cananga latifolia was established. From an aqueous MeOH extract of C. latifolia
      stem bark, six compounds were isolated along with nine known compounds. These
      were identified by using spectroscopic analyses as: (2E,6E,10R)-11-butoxy-10
      hydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid methyl ester, (2E,6E)-3,7,11
      trimethyl-10-oxododeca-2,6-dienoic acid methyl ester, (2E)-3-methyl-5-[(1S,2R,6R)
      1,2,6-trimethyl-3-oxocyclohexyl]-pent-2-enoic acid methyl ester, 1beta-hydroxy-3
      oxo-4beta, 5alpha,7alpha-H-eudesmane 11-O-alpha-l-rhamnopyranoside, 4-epi
      aubergenone 11-O-2',3'-di-O-acetyl-alpha-l-rhamnopyranoside and 4-epi-aubergenone
      11-O-2',4'-di-O-acetyl-alpha-l-rhamnopyranoside. Three of the previously known
      compounds, (2E,6E,10R)-10-hydroxy-3,7,11-trimethyldodeca-2,6,11-trienoaic acid
      methyl ester, (2E,6E,10R)-10,11-dihydroxy-3,7,11-trimethyldodeca-2,6-dienoic acid
      and (2E,6S)-3-methyl-6-hydroxy-6-[(2R,5R)-5-(2-hydroxypropan-2-yl)-2
      methyltetrahydrofuran-2-yl]-hex-2-enoaic acid methyl ester have now been found in
      a plant species. Ultra performance liquid chromatography-quadruple time-of-flight
      mass spectroscopy (UPLC-QTOF/MS) analysis of the chemical constituents of C.
      latifolia showed that several were predominant in the sub-fractions of a C.
      latifolia stem bark extract. 

PMID- 23859263
TI  - Radical-based regioselective C-H functionalization of electron-deficient
      heteroarenes: scope, tunability, and predictability.
AB  - Radical addition processes can be ideally suited for the direct functionalization
      of heteroaromatic bases, yet these processes are only sparsely used due to the
      perception of poor or unreliable control of regiochemistry. A systematic
      investigation of factors affecting the regiochemistry of radical
      functionalization of heterocycles using alkylsulfinate salts revealed that
      certain types of substituents exert consistent and additive effects on the
      regioselectivity of substitution. This allowed us to establish guidelines for
      predicting regioselectivity on complex pi-deficient heteroarenes, including
      pyridines, pyrimidines, pyridazines, and pyrazines. Since the relative
      contribution from opposing directing factors was dependent on solvent and pH, it
      was sometimes possible to tune the regiochemistry to a desired result by
      modifying reaction conditions. This methodology was applied to the direct,
      regioselective introduction of isopropyl groups into complex, biologically active
      molecules, such as diflufenican (44) and nevirapine (45). 

PMID- 23859264
TI  - Protein concentration and protein-exposed hydrophobicity as dominant parameters
      determining the flocculation of protein-stabilized oil-in-water emulsions.
AB  - DLVO theory is often considered to be applicable to the description of
      flocculation of protein-stabilized oil-in-water emulsions. To test this,
      emulsions made with different globular proteins (beta-lactoglobulin, ovalbumin,
      patatin, and two variants of ovalbumin) were compared under different conditions
      (pH and electrolyte concentration). As expected, flocculation was observed under
      conditions in which the zeta potential is decreased (around the isoelectric point
      and at high ionic strength). However, the extent of flocculation at higher ionic
      strength (>50 mM NaCl) decreased with increasing protein-exposed hydrophobicity.
      A higher exposed hydrophobicity resulted in a higher zeta potential of the
      emulsion droplets and consequently increased stability against flocculation.
      Furthermore, the addition of excess protein strongly increased the stability
      against salt-induced flocculation, which is not described by DLVO theory. In the
      protein-poor regime, emulsions showed flocculation at high ionic strength (>100
      mM NaCl), whereas emulsions were stable against flocculation if excess protein
      was present. This research shows that the exposed hydrophobicity of the proteins
      and the presence of excess protein affect the flocculation behavior. 

PMID- 23859265
TI  - Iridium-catalyzed hydrogen transfer: synthesis of substituted benzofurans,
      benzothiophenes, and indoles from benzyl alcohols.
AB  - An iridium-catalyzed hydrogen transfer has been developed in the presence of p
      benzoquinone, allowing the synthesis of a diversity of substituted benzofurans,
      benzothiophenes, and indoles from substituted benzylic alcohols. 

PMID- 23859266
TI  - Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide
      a therapeutic advantage: a cell line study in four glioblastoma multiforme (GBM)
      cell lines.
AB  - PURPOSE: To determine if ultra-fractionation using repeated pulses of radiation
      (10 * 0.2 Gray [Gy]) would be more cytotoxic than continuously-delivered
      radiation to the same total dose (2 Gy) in four glioma cell lines. MATERIALS AND
      METHODS: Human T98G, U373, U87MG and U138MG cells were conventionally X
      irradiated with 0.1-8 Gy and clonogenic survival assessed. Next, cells were
      treated with either a single dose of 2 Gy or 10 pulses of 0.2 Gy using a 3-min
      inter-pulse interval and DNA (Deoxyribonucleic acid) repair (pHistone H2A.X), G2
      phase cell cycle checkpoint arrest (pHistone H3) and apoptosis (caspase-3)
      compared between the two regimens. A dose of 0.2 Gy was selected as this reflects
      the hyper- radiosensitivity (HRS)/increased radioresistance (IRR) transition
      point of the low-dose cell survival curve. RESULTS: T98G, U87MG and U138MG
      exhibited distinct HRS responses and survival curves were well-described by the
      Induced Repair model. Despite the prolonged delivery time, ultra-fractionation
      (10 * 0.2 Gy) was equally effective as a single continuously-delivered 2 Gy dose.
      However, ultra-fractionation was more effective when given for five consecutive
      days to a total dose of 10 Gy. The increased effectiveness of ultra-fractionation
      could not be attributed directly to differences in DNA damage, repair processes
      or radiation-induced apoptosis. CONCLUSIONS: Ultra-fractionation (10 * 0.2 Gy) is
      an effective modality for killing glioma cell lines compared with standard 2 Gy
      dosing when multiple days of treatment are given.

PMID- 23859267
TI  - Drug target prioritization in Plasmodium falciparum through metabolic network
      analysis, and inhibitor designing using virtual screening and docking approach.
AB  - The genome sequence of Plasmodium falciparum reveals that many metabolic pathways
      are unique as compared to its human host. Metabolic Network Analysis was carried
      out to find the essential enzymes critical for the survival of the pathogen. In
      the present study, choke point and load point analysis was used to locate
      putative targets. The identified targets were further checked to confirm that no
      alternate pathway or human homolog exists. Among the top 15 enzymes obtained from
      this analysis, we have selected P. falciparum orotidine-5'-monophosphate
      decarboxylase (PfODCase) enzyme as it is sequentially and structurally different
      from that of humans, for searching novel inhibitors. A five-point 3D
      pharmacophore was generated for the crystal structure of PfODCase complexes with
      uridine-5'-monophosphate (U5P). The binding site environment shows three H-bond
      acceptors, one H-bond donor and one negative ionizable feature. This
      pharmacophore model was used as a 3D query to perform virtual screening
      experiments against 2,664,779 standard lead compounds obtained from the freely
      available ZINC database. Top 10 hits obtained from virtual screening were
      selected for molecular docking experiments against PfODCase in order to verify
      their results and to have a better insight into their binding modes. Here,
      docking of U5P with PfODCase is used as a control. We have identified six
      compounds, among them, few are U5P analogs and others are novel ones with diverse
      scaffolds. The key residues: Lys42, Asp20, Lys72, Ser127, Ala184, Gln185 and
      Arg203 at the main binding pocket of PfODCase are responsible for better
      stability of diverse ligands. These compounds according to their free energy of
      binding could serve as potent leads for designing novel inhibitors against
      malarial ODCase enzyme. 

PMID- 23859268
TI  - Reconn: a cytoscape plug-in for exploring and visualizing reactome.
AB  - Interface and visualization tools usually provide static representations of
      biological pathways, which can be a severe limitation: fixed pathway boundaries
      are used without consensus about the elements that should be included in a
      particular pathway; one cannot generate new pathways or produce selective views
      of existing pathways. Also, the tools are not capable of integrating multiple
      levels that conceptually can be distinguished in biological systems. We present
      ReConn, an interface and visualization tool for a flexible analysis of large data
      at multiple biological levels. ReConn (Reactome Connector) is an open source
      extension to Cytoscape which allows user friendly interaction with the Reactome
      database. ReConn can use both predefined Reactome pathways as well as generate
      new pathways. A pathway can be derived by starting from any given metabolite and
      existing pathways can be extended by adding related reactions. The tool can also
      retrieve alternative routes between elements of a biological network. Such an
      option is potentially applicable in the design and analysis of knockout
      experiments. ReConn displays information about multiple levels of the system in
      one view. With these dynamic features ReConn addresses all of the above mentioned
      limitations of the interface tools. 

PMID- 23859269
TI  - A variational Bayes beta mixture model for feature selection in DNA methylation
      studies.
AB  - An increasing number of studies are using beadarrays to measure DNA methylation
      on a genome-wide basis. The purpose is to identify novel biomarkers in a wide
      range of complex genetic diseases including cancer. A common difficulty
      encountered in these studies is distinguishing true biomarkers from false
      positives. While statistical methods aimed at improving the feature selection
      step have been developed for gene expression, relatively few methods have been
      adapted to DNA methylation data, which is naturally beta-distributed. Here we
      explore and propose an innovative application of a recently developed variational
      Bayesian beta-mixture model (VBBMM) to the feature selection problem in the
      context of DNA methylation data generated from a highly popular beadarray
      technology. We demonstrate that VBBMM offers significant improvements in
      inference and feature selection in this type of data compared to an Expectation
      Maximization (EM) algorithm, at a significantly reduced computational cost. We
      further demonstrate the added value of VBBMM as a feature selection and
      prioritization step in the context of identifying prognostic markers in breast
      cancer. A variational Bayesian approach to feature selection of DNA methylation
      profiles should thus be of value to any study undergoing large-scale DNA
      methylation profiling in search of novel biomarkers. 

PMID- 23859270
TI  - A case-based reasoning system for genotypic prediction of HIV-1 co-receptor
      tropism.
AB  - Accurate co-receptor tropism (CRT) determination is critical for making treatment
      decisions in HIV management. We created a genotypic tropism prediction tool by
      utilizing the case-based reasoning (CBR) technique that attempts to solve new
      problems through applying the solution from similar past problems. V3 loop
      sequences from 732 clinical samples with diverse characteristics were used to
      build a case library. Additional sequence and molecular properties of the V3 loop
      were examined and used for similarity assessment. A similarity metric was defined
      based on each attribute's frequency in the CXCR4-using viruses. We implemented
      three other genotype-based tropism predictors, support vector machines (SVM),
      position specific scoring matrices (PSSM), and the 11/25 rule, and evaluated
      their performance as the ability to predict CRT compared to Monogram's enhanced
      sensitivity Trofile((r)) assay (ESTA). Overall concordance of the CBR based
      tropism prediction algorithm was 81%, as compared to ESTA. Sensitivity to detect
      CXCR4 usage was 90% and specificity was at 73%. In comparison, sensitivity of the
      SVM, PSSM, and the 11/25 rule were 85%, 81%, and 36% respectively while achieving
      a specificity of 90% by SVM, 75% by PSSM, and 97% by the 11/25 rule. When we
      evaluated these predictors in an unseen dataset, higher sensitivity was achieved
      by the CBR algorithm (87%), compared to SVM (82%), PSSM (76%), and the 11/25 rule
      (33%), while maintaining similar level of specificity. Overall this study
      suggests that CBR can be utilized as a genotypic tropism prediction tool, and can
      achieve improved performance in independent datasets compared to model or rule
      based methods. 

PMID- 23859271
TI  - De novo sequencing with limited number of post-translational modifications per
      peptide.
AB  - De novo sequencing derives the peptide sequence from a tandem mass spectrum
      without the assistance of protein databases. This analysis has been indispensable
      for the identification of novel or modified peptides in a biological sample.
      Currently, the speed of de novo sequencing algorithms is not heavily affected by
      the number of post-translational modification (PTM) types in consideration.
      However, the accuracy of the algorithms can be degraded due to the increased
      search space. Most peptides in a proteomics research contain only a small number
      of PTMs per peptide, yet the types of PTMs can come from a large number of
      choices. Therefore, it is desirable to include a large number of PTM types in a
      de novo sequencing algorithm, yet to limit the number of PTM occurrences in each
      peptide to increase the accuracy. In this paper, we present an efficient de novo
      sequencing algorithm, DeNovoPTM, for such a purpose. The implemented software is
      downloadable from http://www.cs.uwaterloo.ca/~l22he/denovo_ptm . 

PMID- 23859272
TI  - Dynamically searching for a domain for protein function prediction.
AB  - The availability of large amounts of protein-protein interaction (PPI) data makes
      it feasible to use computational approaches to predict protein functions. The
      base of existing computational approaches is to exploit the known function
      information of annotated proteins in the PPI data to predict functions of un
      annotated proteins. However, these approaches consider the prediction domain
      (i.e. the set of proteins from which the functions are predicted) as unchangeable
      during the prediction procedure. This may lead to valuable information being
      overwhelmed by the unavoidable noise information in the PPI data when predicting
      protein functions, and in turn, the prediction results will be distorted. In this
      paper, we propose a novel method to dynamically predict protein functions from
      the PPI data. Our method regards the function prediction as a dynamic process of
      finding a suitable prediction domain, from which representative functions of the
      domain are selected to predict functions of un-annotated proteins. Our method
      exploits the topological structural information of a PPI network and the semantic
      relationship between protein functions to measure the relationship between
      proteins, dynamically select a suitable prediction domain and predict functions.
      The evaluation on real PPI datasets demonstrated the effectiveness of our
      proposed method, and generated better prediction results. 

PMID- 23859273
TI  - A heuristic cluster-based EM algorithm for the planted (l, d) problem.
AB  - The planted motif search problem arises from locating the transcription factor
      binding sites (TFBSs) which are crucial for understanding the gene regulatory
      relationship. Many attempts in using expectation maximization for TFBSs discovery
      are successful in past. However, identifying highly degenerate motifs and
      reducing the effect of local optima are still an arduous task. To alleviate the
      vulnerability of EM to local optima trapping, we present a heuristic cluster
      based EM algorithm, CEM, which refines the cluster subsets in EM method to
      explore the best local optimal solution. Based on experiments using both
      synthetic and real datasets, our algorithm demonstrates significant improvements
      in identifying the motif instances and performs better than current widely used
      algorithms. CEM is a novel planted motif finding algorithm, which is able to
      solve the challenging instances and easy to parallel since the process of solving
      each cluster subset is independent. 

PMID- 23859274
TI  - A fast and accurate algorithm for diploid individual haplotype reconstruction.
AB  - Haplotypes can provide significant information in many research fields, including
      molecular biology and medical therapy. However, haplotyping is much more
      difficult than genotyping by using only biological techniques. With the
      development of sequencing technologies, it becomes possible to obtain haplotypes
      by combining sequence fragments. The haplotype reconstruction problem of diploid
      individual has received considerable attention in recent years. It assembles the
      two haplotypes for a chromosome given the collection of fragments coming from the
      two haplotypes. Fragment errors significantly increase the difficulty of the
      problem, and which has been shown to be NP-hard. In this paper, a fast and
      accurate algorithm, named FAHR, is proposed for haplotyping a single diploid
      individual. Algorithm FAHR reconstructs the SNP sites of a pair of haplotypes one
      after another. The SNP fragments that cover some SNP site are partitioned into
      two groups according to the alleles of the corresponding SNP site, and the SNP
      values of the pair of haplotypes are ascertained by using the fragments in the
      group that contains more SNP fragments. The experimental comparisons were
      conducted among the FAHR, the Fast Hare and the DGS algorithms by using the
      haplotypes on chromosome 1 of 60 individuals in CEPH samples, which were released
      by the International HapMap Project. Experimental results under different
      parameter settings indicate that the reconstruction rate of the FAHR algorithm is
      higher than those of the Fast Hare and the DGS algorithms, and the running time
      of the FAHR algorithm is shorter than those of the Fast Hare and the DGS
      algorithms. Moreover, the FAHR algorithm has high efficiency even for the
      reconstruction of long haplotypes and is very practical for realistic
      applications. 

PMID- 23859275
TI  - Effect of chitosan incorporation and scaffold geometry on chondrocyte function in
      dense collagen type I hydrogels.
AB  - Tissue engineering approaches for articular cartilage (AC) repair using collagen
      type I (Coll)-based hydrogels are limited by their low collagen fibril density
      (CFD; <0.5 wt%) and their poor capacity to support chondrocyte differentiation.
      Chitosan (CTS) is a well-characterized polysaccharide that mimics the
      glycosaminoglycans (GAGs) present in native AC extracellular matrix and exhibits
      chondroprotective properties. Here dense Coll/CTS hydrogel discs (16 mm diameter,
      140-250 MUm thickness) with CFD (~6 wt%) approaching that of AC were developed to
      investigate the effect of CTS content on the growth and differentiation of three
      dimensionally seeded RCJ3.1C5.18 chondroprogenitor cells. Compared to dense Coll
      alone, cells seeded within Coll/CTS showed increased viability and metabolic
      activity, as well as a decrease in cell-mediated gel contraction.
      Immunohistochemistry for collagen type II, in combination with Safranin O
      staining and GAG quantification, indicated greater chondroprogenitor
      differentiation within Coll/CTS, compared to cells seeded within Coll alone. The
      complex interplay between scaffold geometry, microstructure, composition,
      mechanical properties and cell function was further evaluated by rolling dense
      planar sheets to prepare cylindrically shaped constructs having clinically
      relevant diameters (3-5 mm diameter, 9 mm height). The compressive modulus of the
      cylindrically shaped constructs decreased significantly after 7 days in culture,
      and remained unchanged up to 21 days for each scaffold composition. Unlike Coll,
      cells seeded within Coll/CTS showed greater viability along the entire radial
      extent of the cylindrical rolls and increased GAG production at each time point.
      While GAG content decreased over time and reduced cell viability was observed
      within the core region of all cylindrical rolls, the incorporation of CTS
      diminished both these effects. In summary, these findings provide insight into
      the challenges involved when scaling up scaffolds designed and optimised in vitro
      for tissue repair. 

PMID- 23859276
TI  - Parental effects on the larval performance of a tapeworm in its copepod first
      host.
AB  - Parents can influence the phenotype of their offspring through various
      mechanisms, besides the direct effect of heredity. Such parental effects are
      little explored in parasitic organisms, perhaps because in many parasites, per
      capita investment into offspring is low. I investigated whether parental
      identity, beyond direct genetic effects, could explain variation in the
      performance of the tapeworm Schistocephalus solidus in its first intermediate
      host, a copepod. I first determined that two breeding worms could be separated
      from one another after ~48 h of in vitro incubation and that the isolated worms
      continued producing outcrossed eggs, that is, rates self-fertilization did not
      increase after separation. Thus, from a breeding pair, two sets of genetically
      comparable eggs can be collected that have unambiguous parental identities. In an
      infection experiment, I found that the development of larval worms tended to vary
      between the two parental worms within breeding pairs, but infection success and
      growth rate in copepods did not. Accounting for this parental effect decreased
      the estimated heritability for development by nearly half. These results suggest
      that larval performance is not simply a function of a worm's genotype; who
      mothered or fathered an offspring can also affect offspring fitness,
      contradicting the perhaps naive idea that parasites simply produce large
      quantities of uniformly low-quality offspring. 

PMID- 23859277
TI  - Acute ischemic complications of PCI and CABG: who should cover whom for coronary
      revascularization?
AB  - INTRODUCTION: Percutaneous coronary intervention (PCI) has historically required
      cardiothoracic backup in the event of ischemic complications. However, many
      complications occurring during PCI can now be effectively treated at the time of
      the indexed procedure. Equally, ischemic complications, which occur following
      coronary artery bypass grafting (CABG), which were previously treated medically
      or with reoperation, may now also be effectively treated by acute PCI. AIMS AND
      METHODS: To identify the rate, cause, treatment, and outcomes of ischemic
      complications from PCI or isolated CABG procedures undertaken from January 2004
      to January 2011 where there was immediate crossover from PCI to CABG or vice
      versa, and to determine from the indexed revascularization procedure, whether or
      not the ischemic complications were rectified by either CABG with respect to PCI
      or PCI with respect to CABG. RESULTS: Three hundred fifty-six PCI major ischemic
      complications were identified. Three hundred forty-seven (97.5%) were rectified
      percutaneously and 9 (2.5%) required emergency CABG. The commonest reason for
      emergency CABG was occlusive dissection (n=7). Of the 9 patients that underwent
      emergency CABG, 3 patients (33.3%) died. Forty CABG major ischemic complications
      were identified. Twenty-seven (67.5%) were treated medically. Thirteen (32.5%)
      underwent diagnostic angiography. The etiology of the ischemia was found in all
      cases. Consequently, 2 underwent reoperation, one was treated medically, and 10
      underwent acute PCI. CONCLUSION: Acute coronary ischemia remains a small but
      significant complication of both PCI and CABG. Resolution of ischemia requires
      prompt diagnosis and early discussion between cardiothoracic surgeon and cardiac
      interventionalist to determine the safest and therefore most appropriate way to
      resolve the problem.

PMID- 23859278
TI  - Boosting restraint norms: a community-delivered campaign to promote booster seat
      use.
AB  - OBJECTIVE: The objective of this study was to evaluate the effectiveness of a
      theoretically grounded community-delivered marketing campaign to promote belt
      positioning booster seat (BPB) use among vulnerable populations when disseminated
      by community members. METHODS: A prospective, nonrandomized community
      intervention trial was conducted to evaluate the "Boosting Restraint Norms"
      social marketing campaign delivered by community partners in Norristown,
      Pennsylvania (intervention community), between October 2008 and November 2008.
      York, Pennsylvania, served as the comparison community. In total, 800 vehicles
      with 822 children aged 4 to 7 years were observed for BPB use, the primary
      outcome of interest, at baseline (September 2008) and at 6 months after
      intervention (April 2009). RESULTS: During the study period, a 28 percent
      increase in the prevalence of BPB use at 6 months was observed in the
      intervention community with no change in the prevalence of BPB use in the
      comparison community. After adjustment for child age and gender, vehicle type,
      driver gender, and driver level, BPB use increased from 39 to 50 percent in the
      intervention community. CONCLUSIONS: The "Boosting Restraint Norms" social
      marketing campaign, distributed through community organizations combined with
      caregiver education and a one-time free distribution of BPBs, was effective in
      increasing BPB use. This study demonstrates the feasibility of utilizing
      community organizations with established audiences to spread the "No Regrets"
      messaging of the campaign in the community. This study also indicates that
      spreading evidence-based messages in this manner may effectively change behavior
      in populations that are often hard to reach. Future studies are needed in which
      this methodology is tested in additional communities and rural settings.

PMID- 23859279
TI  - Ischemic stroke penumbra and extracorporeal ozone treatment.
AB  - The course of events in ischemic strokes is normally seen from a point in which
      the penumbra is already in place. Since there is no known treatment for edema
      reduction, mainstream medicine focuses on re-opening the occluded vessel. Here we
      show that reducing the penumbra saves neuronal units from undergoing apoptosis. 

PMID- 23859280
TI  - Bridging neuroanatomy, neuroradiology and neurology: three-dimensional
      interactive atlas of neurological disorders.
AB  - Understanding brain pathology along with the underlying neuroanatomy and the
      resulting neurological deficits is of vital importance in medical education and
      clinical practice. To facilitate and expedite this understanding, we created a
      three-dimensional (3D) interactive atlas of neurological disorders providing the
      correspondence between a brain lesion and the resulting disorder(s). The atlas
      contains a 3D highly parcellated atlas of normal neuroanatomy along with a brain
      pathology database. Normal neuroanatomy is divided into about 2,300 components,
      including the cerebrum, cerebellum, brainstem, spinal cord, arteries, veins,
      dural sinuses, tracts, cranial nerves (CN), white matter, deep gray nuclei,
      ventricles, visual system, muscles, glands and cervical vertebrae (C1-C5). The
      brain pathology database contains 144 focal and distributed synthesized lesions
      (70 vascular, 36 CN-related, and 38 regional anatomy-related), each lesion
      labeled with the resulting disorder and associated signs, symptoms, and/or
      syndromes compiled from materials reported in the literature. The initial view of
      each lesion was preset in terms of its location and size, surrounding surface and
      sectional (magnetic resonance) neuroanatomy, and labeling of lesion and
      neuroanatomy. In addition, a glossary of neurological disorders was compiled and
      for each disorder materials from textbooks were included to provide neurological
      description. This atlas of neurological disorders is potentially useful to a wide
      variety of users ranging from medical students, residents and nurses to general
      practitioners, neuroanatomists, neuroradiologists and neurologists, as it
      contains both normal (surface and sectional) brain anatomy and pathology
      correlated with neurological disorders presented in a visual and interactive way.

PMID- 23859281
TI  - Three-dimensional interactive atlas of cranial nerve-related disorders.
AB  - Anatomical knowledge of the cranial nerves (CN) is fundamental in education,
      research and clinical practice. Moreover, understanding CN-related pathology with
      underlying neuroanatomy and the resulting neurological deficits is of vital
      importance. To facilitate CN knowledge anatomy and pathology understanding, we
      created an atlas of CN-related disorders, which is a three-dimensional (3D)
      interactive tool correlating CN pathology with the underlying surface and
      sectional neuroanatomy as well as the resulting neurological deficits. A computer
      platform was developed with: 1) anatomy browser along with the normal brain atlas
      (built earlier); 2) simulator of CN lesions; 3) tools to label CN-related
      pathology; and 4) CN pathology database with lesions and disorders, and the
      resulting signs, symptoms and/or syndromes. The normal neuroanatomy comprises
      about 2,300 3D components subdivided into modules. Cranial nerves contain more
      than 600 components: all 12 pairs of cranial nerves (CN I - CN XII) and the
      brainstem CN nuclei. The CN pathology database was populated with 36 lesions
      compiled from clinical textbooks. The initial view of each disorder was preset in
      terms of lesion location and size, surrounding surface and sectional
      neuroanatomy, and disorder and neuroanatomy labeling. Moreover, path selection
      from a CN nucleus to a targeted organ further enhances pathology-anatomy
      relationships. This atlas of CN-related disorders is potentially useful to a wide
      variety of users ranging from medical students and residents to general
      practitioners, neuroradiologists and neurologists, as it contains both normal
      brain anatomy and CN-related pathology correlated with neurological disorders
      presented in a visual and interactive way. 

PMID- 23859282
TI  - Proton magnetic resonance spectroscopy (H-MRS) in chronic schizophrenia. A single
      voxel study in three regions involved in a pathogenetic theory.
AB  - The cognitive dysmetria theory suggests a disconnectivity between the
      dorsolateral prefrontal cortex, thalami and vermis to explain the pathophysiology
      of schizophrenia. This study investigated the metabolic integrity of this
      neurologic circuit in patients with schizophrenia using proton magnetic resonance
      spectroscopy (H-MRS). Twenty-two patients with schizophrenia and twelve control
      subjects were studied. Metabolites concentrations were evaluated by a single
      voxel technique in the prefrontal cortex, thalami and vermis. To our knowledge,
      this is the first H-MRS experience with concomitant evaluation of these regions
      in schizophrenic patients. We found no significant statistical difference in N
      AA, Cho and Cr absolute concentrations and N-AA/Cho, N-AA/Cr and Cho/Cr ratios
      between the schizophrenic patients and control group. At the vermis, we found a
      constant spectrum with low levels of N-AA and higher levels of Cho and Cr. Our
      experience does not clearly support or refute the cognitive dysmetria theory. The
      consistency of metabolic findings in the cerebellar vermis could represent an
      important datum, highlighting the specificity of metabolic and functional
      activity in this region. 

PMID- 23859283
TI  - Accuracy of transcranial ultrasound in the detection of mild white matter lesions
      in newborns.
AB  - Cranial Ultrasound (cUS) may not be sensitive enough to detect subtle white
      matter (WM) injuries. Our study compared serial cUS with MRI at term equivalent
      age (TEA) to determine if it is possible to identify an ultrasound representation
      of subtle diffuse WM injuries such as punctate lesions (PWMLs) and diffuse
      excessive high signal intensity (DEHSI). Fifty-six very preterm infants were
      scanned sequentially from birth to TEA, an MRI was performed at TEA. Each
      echodensity found on cUS was classified as absent, transient (<=7 days), or
      prolonged (>7 days). A transient periventricular echodensity was detected in
      seven infants (12.5%), and a prolonged echodensity in 15 (26.8%). MRI
      examinations were performed in all 56 infants. No altered signal intensity was
      found in 18 infants (32.1%). DEHSI was detected in 14 infants (25%), and PWMLs
      were detected in eight babies (14.3%). Both abnormalities were found in 16
      infants (28.6%). The positive predictive values of the prolonged echodensity for
      DEHSI and PWMLs were 86.7% and 46.7% respectively. However, a significant
      statistical correspondence (p=0.002, Odds Ratio 11.9) was found comparing DEHSI
      with cUS abnormal echodensities. Serial cUS during the neonatal period in preterm
      infants is essential and cannot be replaced with MRI at TEA. MRI seems to be more
      reliable in detecting mild or moderate WM abnormalities. However, serial cUS
      performed by an experienced neonatologist can provide valuable information on
      early WM changes such as prolonged echodensities that could potentially lead to a
      diffuse injury. 

PMID- 23859284
TI  - Unusual case of cerebral aspergillosis with clinical and imaging findings
      mimicking lymphoma.
AB  - A 14-year-old female post-transplant patient with a history of post-transplant
      lymphoproliferative disease/lymphoma presented with fever and lethargy. Computed
      tomography of the brain demonstrated a hypodense lesion with surrounding edema in
      the right periventricular region not seen on a routine study performed two weeks
      earlier. On magnetic resonance imaging (MRI) this lesion was mainly iso-intense
      to gray matter on T2-weighted (T2W) images and demonstrated peripheral contrast
      enhancement. Diffusion restriction was seen within most of the lesion including,
      but not limited to, its periphery. Lesion location and MRI characteristics,
      particularly on T2W and diffusion sequences, were suggestive of lymphoma. The
      patient's history of post-transplant lymphoproliferative disorder also supported
      this diagnosis. However, in view of the patient's immunocompromised state, rapid
      onset of symptoms, and recent normal CT scan of the brain, infection was also
      entertained. Biopsy revealed short branching hyphae consistent with
      aspergillosis. This case is interesting as the MRI restriction pattern and the
      patient's history were more suggestive of lymphoma, but in reality the lesion
      represented an evolving aspergillosis abscess. Biopsy was necessary to further
      proceed with appropriate medical management, which is significantly different for
      the two entities. 

PMID- 23859285
TI  - Evaluation of the pituitary gland using magnetic resonance imaging: T1-weighted
      vs. VIBE imaging.
AB  - Volumetric interpolated breath-hold examination (VIBE) is used for abdominal
      imaging as a fast and efficient modality. Evaluation of brain lesions using VIBE
      is not common and its use for the pituitary gland has not yet been addressed. Our
      goal was to compare coronal T1-weighted (T1W) and VIBE images in patients
      undergoing studies of the pituitary gland. We hypothesized that, for this
      purpose, VIBE is superior to T1W images. T1W and VIBE images of the pituitary
      gland in 32 patients were evaluated. The two sequences were compared with
      specific attention to: contrast enhancement (gland and cavernous sinuses) and
      ability to view the anatomy of the cavernous sinuses. In patients with
      macroadenomas, visualization of the optic chiasm was also assessed. Images were
      rated as: VIBE being better, equal, or worse in comparison to T1W images. We also
      compared VIBE and T1W images specifically looking at micro/macro-adenomas and
      post-surgical patients. Statistical analysis was performed using chi-square
      statistics. Of the 32 patients, the VIBE sequence showed superior contrast
      enhancement in 18 patients, six were found as being equal to T1W, and in eight
      instances VIBE was found to be worse than T1W. These results were statistically
      significant (p=.02). When looking at micro/macro-adenomas and post-surgical
      patients specifically, there was a trend to VIBE being superior to T1W but these
      data were not statistically significant. Visualization of chiasm in macroadenomas
      was similar for both techniques. VIBE was significantly superior to T1W with
      respect to pituitary and cavernous sinus contrast enhancement and cavernous sinus
      anatomy. A trend towards VIBE being superior in the evaluation of adenomas (pre-
      and post-operative) was seen, but it was not statistically significant. This is
      likely due to the small population size. 

PMID- 23859286
TI  - Intrasellar fat graft gains weight with the patient: imaging features.
AB  - We describe a 56-year-old man with an intrasellar craniopharyngioma who underwent
      transphenoidal resection and abdominal fat grafting of the dural opening. Follow
      up MRI showed hypertrophy of the sellar fat graft concurrent with the patient's
      weight gain. To our best of knowledge sellar fat graft hypertrophy has not been
      reported before. 

PMID- 23859287
TI  - Spontaneous resolution of Chiari type 1 malformation. A case report and
      literature review.
AB  - We describe a 62-year-old woman who presented with a history of ataxia, dizziness
      and urinary urgency. Neurological examination disclosed a positive Romberg sign,
      ataxia and postural instability. A magnetic resonance imaging (MRI) scan showed
      Chiari type 1 malformation (CM1). Forty-eight months later, the patient was
      clinically improved and underwent a second MRI examination, which showed complete
      resolution of the Chiari 1 malformation. Spontaneous resolution of CM1 is
      exceptionally rare and has to be considered in the radiological and clinical
      management. 

PMID- 23859288
TI  - Venous hypertension may be a factor in aneurysmal rupture. A case report.
AB  - This report describes cerebral aneurysmal rupture with asymmetry of ipsilateral
      dural sinus hypoplasia using quantitative color-coded I-Flow cerebral venography
      to identify the venous pressure gradient. We suggest the pressure gradient may be
      a potential factor in cerebral aneurysmal rupture. We used I-Flow quantitative
      cerebral venography to measure the venous pressure gradient during acute cerebral
      aneurysmal rupture and post embolization in a 67-year-old woman who presented
      with clinical symptoms of left third nerve palsy for several days with mild
      headache initially without subarachnoid hemorrhage. We encountered a high venous
      pressure gradient of severe ipsilateral dural sinus hypoplasia during acute
      rupture of a posterior communicating aneurysm. Venous dural sinus asymmetry has
      been considered a congenital benign and non-pathological condition. However, this
      case may present severe hypoplasia of the dural sinus with potential pressure
      gradient in some unusual condition. A high venous pressure gradient may be
      another factor in cerebral aneurysmal rupture. 

PMID- 23859289
TI  - Management of unruptured brain aneurysms: retrospective analysis of a single
      centre experience.
AB  - Embolization is very effective in preventing bleeding of unruptured aneurysms
      with lower rates of mortality and morbidity than surgical treatment. Neurosurgery
      remains, however, a good alternative. This retrospective analysis examined data
      stored the digital database of Bellaria Hospital Radiology Department, evaluating
      patients, treatments and devices used as well as outcomes and complications.
      Therapy should be tailored to each individual case to offer each patient the best
      treatment. Out of 265 unruptured intracranial aneurysms detected, 182 were
      treated by embolization. 16 cases presented complications (12 only radiologically
      found); severe clinical consequences occurred in 3%: one ischaemia and five
      haemorrhages. Conservative treatment was adopted in 21 patients. Long-term follow
      up is mandatory as aneurysms could increase their size and develop an irregular
      morphology in ten years' time. Endovascular embolization is a very effective
      treatment with positive outcomes in the majority of cases and a percentage of
      retreatments of 8%. In order to increase the number of successful cases, a
      multidisciplinary cooperation with neurosurgeons is strongly recommended. 

PMID- 23859290
TI  - Revascularized giant aneurysm of the anterior communicating artery after surgery
      and embolization, occluded by placement of a Leo+Baby intracranial stent. A case
      report.
AB  - Balt (Montmorency, France) recently manufactured the Leo+Baby dedicated
      intracranial stent for arteries with a calibre between 1.5 and 3.10 mm. We
      describe a patient with a partially thrombosed giant sacciform aneurysm of the
      anterior communicating artery treated without success by surgery and coil
      embolization subsequently occluded by placement of a Leo+Baby stent (Balt,
      Montmorency, France). A 56-year-old man presented with a giant aneurysm in the
      anterior communicating artery region. Following successive surgical intervention
      and embolization procedures the patient was referred to us with a revascularized
      aneurysm measuring 15*9*8 cm. To stabilize the endovascular occlusion a combined
      treatment was scheduled with coil embolization and stent deployment after dual
      antiplatelet therapy started five days before the interventional procedure.
      Treatment was undertaken two weeks later under general anaesthesia and total
      heparinization. A microcatheter was inserted into the aneurysmal sac and four
      metal coils were released for a total of 61cm obtaining almost complete occlusion
      of the aneurysm from the circulation. A Leo+Baby stent (2.5*18 mm) was
      subsequently deployed across the aneurysm neck. At follow-up angiography two
      months later the aneurysm appeared substantially excluded from the arterial
      circulation except for a small portion in the neck. Six months later, four months
      after suspending antiplatelet therapy, follow-up angiography disclosed the
      complete exclusion of the aneurysm from the circulation. Deployment of the new
      ministent through the same microcatheter used to release the coils made the
      interventional procedure simpler and faster. 

PMID- 23859291
TI  - Endovascular treatment of a small aneurysm of the superior cerebellar artery with
      a flow-diverter device. A case report.
AB  - We describe the case of a 62-year-old woman who presented with a small fusiform
      left superior cerebellar artery (SCA) aneurysm. Aneurysms located on the SCA are
      uncommon and their presentation, natural history and clinical management are
      poorly understood. Reports on the endovascular or surgical management of SCA
      aneurysms are rare and usually incorporated in clinical series of basilar artery
      or posterior circulation aneurysms. The patient was treated by delivery of a flow
      diverter Pipeline Embolization Device (PED - Chestnut Medical/ev3) at the origin
      of vessel. She had no procedural complications and the aneurysm volume was
      reduced. This paper presents additional evidence to literature reports suggesting
      that the new endovascular flow-diverter devices are an effective and well
      tolerated treatment for complex aneurysms. Our review contributes data on the
      incidence of recurrence as a measure of long-term efficacy of this therapeutic
      approach. 

PMID- 23859292
TI  - A juvenile case of cerebellar arteriovenous malformation with gradual onset of
      dysphoria and headache.
AB  - A 25-year-old woman was admitted because of frequent vomiting and headache which
      had lasted over one week. She had initially clear consciousness but slowly
      progressive mild headache and dysphoria. Emergency cranial CT revealed a 4 cm
      haematoma in the left cerebellar hemisphere. CT angiography showed a 2*2 cm nidus
      of an arteriovenous malformation (AVM) in the left hemisphere fed from the left
      posterior inferior cerebellar artery and draining into the inferior hemispheric
      vein. We performed a surgical resection of the AVM after decompression therapy to
      counteract the brain oedema. She recovered completely without any neurological
      deficits. This case recalls the importance of cooperation between diagnostic
      neuroradiology and neurosurgery in emergency, considering AVM, even if
      infrequent, among possible diseases. 

PMID- 23859293
TI  - Endovascular treatment of vertebro-vertebral arteriovenous fistula. A report of
      three cases and literature review.
AB  - This report describes endovascular approaches for occlusion of vertebro-vertebral
      arteriovenous fistula (VV-AVF) in a series of three cases and a review of the
      literature. Complete neuroimaging assessment, including CT, MR and DSA was
      performed in three patients (two female, one male) with VV-AVF. Based on DSA
      findings, the VV-AVF were occluded by endovascular positioning of detachable
      balloons (case 1), coils (case 2), or a combination of both (case 3) with parent
      artery patency in two out of three cases. In this small series, endovascular
      techniques for occlusion of VV-AVF were safe and effective methods of treatment.
      To date, there are no guidelines on the best treatment for VV-AVF. Detachable
      balloons, endovascular coiling, combined embolization procedures could all be
      considered well-tolerated treatments. 

PMID- 23859294
TI  - MR assessment of lumbar disk herniation treated with oxygen-ozone diskolysis: the
      role of DWI and related ADC versus intervertebral disk volumetric analysis for
      detecting treatment response.
AB  - We prospectively assessed the diagnostic criteria of morphologic MRI study (MMS)
      and the accuracy of DWI and related ADC values (DWI-ADC) versus intervertebral
      disk volumetric analysis (IDVA) for predicting shrinkage of lumbar disk
      herniation treated with oxygen-ozone (O2-O3) diskolysis. Sixty-eight patients (36
      men and 32 women; mean age 39) with lumbosciatica underwent O2-O3 diskolysis. The
      six-month MRI follow-up was performed with FSE-T2 and T2-fat, SE-T1 and DWI
      weighted images. IDVA was determined using OsiriX((r)). Diagnostic criteria and
      accuracy were evaluated with regards to DWI and related ADC in detecting response
      to ozone therapy. Fifty-eight of 68 patients had successful outcomes
      (responders), whereas ten patients showed unsatisfactory outcomes (non
      responders). MMS showed that a centrally located herniated disk and grade 1 nerve
      root compression were more common in the responder group (p < 0.05). DWI-ADC and
      IDVA showed statistically significant shrinkage in the sixth month of follow-up
      (p < 0.05) with a mean ADC value reduction of 2.10 * 10(-3) mm(2)/s +/- 0.19 SD
      in the second month of follow-up (p < 0.05). DWI-ADC had an accuracy of 0.81 in
      detecting response to therapy around the second month of follow-up. DWI-ADC
      appear to be useful adjuncts to MMS in the follow-up of patients undergoing O2-O3
      diskolysis. 

PMID- 23859296
TI  - Prompt enteral nutrition may reduce morbidity and mortality in many acute
      illnesses.

PMID- 23859295
TI  - Historical aspects and relevance of the human coronary collateral circulation.
AB  - In 1669, anastomoses between the right and left coronary artery were first
      documented by Richard Lower of Amsterdam. Using post-mortem imaging, a debate
      followed on the existence of structural inter-coronary anastomoses, which was not
      resolved before the first half of the 20 ieth century in case of the presence of
      coronary artery disease (CAD), and not before the early 1960 ies in case of the
      normal human coronary circulation by William Fulton. Functional coronary
      collateral measurements during coronary interventions were first performed only
      in the 1970 ies, respectively in the early 1980 ies. In humans, the existence of
      functional coronary collaterals in the absence of CAD has not been documented
      before 2003. Though the coronary collateral circulation has been recognized as an
      alternative source of blood supply to ischemic myocardium, its prognostic
      significance for the CAD population as a whole has been controversial until
      recently. The debate was due to different populations examined (acute versus
      chronic CAD, varying severity of CAD), to variable definitions of the term
      "prognosis", to insufficient statistical power of the investigation with rare
      occurrence of prognostic endpoints, to short duration of follow-up and to blunt
      instruments employed for collateral assessment. Individually, it has been
      acknowledged that a well functioning collateral supply to a myocardial area at
      risk for necrosis reduces infarct size, preserves ventricular function, prevents
      ventricular remodelling and aneurysm formation. Collectively, evidence has
      accumulated only recently that an extensive coronary collateral circulation is a
      beneficial prognosticator quoad vitam. In a recent meta-analysis on the topic,
      the risk ratio to die from any cause for high vs low or absent collateralization
      in patients with subacute myocardial infarction was 0.53 (95% confidence interval
      0.15-1.92; p=0.335), and for patients with acute myocardial infarction, it was
      0.63 (95% confidence interval 0.29-1.39; p=0.257)  the relative risk to die from
      any cause for well vs poorly developed collaterals in patients with stable CAD
      was 0.59 (95% confidence interval 0.39-0.89), p=0.012.

PMID- 23859297
TI  - Computational study of the combustion and atmospheric decomposition of 2
      methylfuran.
AB  - There is a growing interest in alkylfurans as potential biofuels. Recent work has
      highlighted the need for further study of the atmospheric oxidation mechanism of
      2-methylfuran (2MF). This study utilizes the high level composite computational
      methods, G4 and CBS-QB3, to determine the bond dissociation energies for the C-H
      bond in 2MF and the reaction enthalpies and barrier heights of several of the
      known possible initiation reaction pathways. This study also investigates the
      possible subsequent low temperature reaction pathways following the addition of
      OH and then O2 onto the 2MF ring. The placement of the OH and O2 on the ring,
      either cis or trans to each other, dictates the viability of subsequent
      reactions. Of particular interest is the observation that 1,4 H-migrations that
      abstract the hydrogen bound to the same carbon as the OH have abnormally low
      barrier height. This dramatic decrease puts the reaction barrier lower than
      concerted eliminations and 6-membered ring Waddington-type reactions. In
      addition, a novel reaction type, described as a Waddington concerted elimination,
      is reported herein. This reaction, when viable, is generally more favorable than
      other reactions. The results presented here are of interest to combustion
      modelers and atmospheric chemists, particularly those working on aromatic
      hydrocarbons and systems with conjugated double bonds. 

PMID- 23859298
TI  - The relationship between sexual concordance and interoception in anxious and
      nonanxious women.
AB  - INTRODUCTION: Sexual concordance refers to the association between physiological
      and self-reported sexual arousal. Women typically exhibit lower sexual
      concordance scores than men. There is also a sex difference in interoception-
      awareness of (nonsexual) physiological states or responses--such that women,
      compared with men, tend to be less aware of and less accurate at detecting
      changes in their physiological responses. Women with anxiety problems tend to
      have better interoceptive abilities than nonanxious women. AIM: To investigate
      whether women's lower sexual concordance is associated with interoception using a
      sample likely to show high variation in interoceptive abilities. METHOD: Sixteen
      anxious and 15 nonanxious women were presented with twelve 90 seconds sexual and
      nonsexual film clips while their genital response, heart rate, and respiration
      rate were measured. A heartbeat mental tracking task was also employed. MAIN
      OUTCOME MEASURES: Genital response was measured with a vaginal
      photoplethysmograph. Heart rate was measured with an electrocardiogram and
      respiration rate with a thermistor. Participants estimated their physiological
      responses after each film. A mental tracking task was also used to assess
      participants' awareness of heart rate. Within-subject correlations were computed
      for each physiological/self-reported response combination. RESULTS: Overall,
      sexual concordance (i.e., the correlation between genital responses and
      perceptions of genital response) was not significantly associated with heart rate
      awareness or respiration rate awareness. Anxious women did not exhibit
      significantly higher sexual concordance or heart rate awareness than nonanxious
      women; the nonanxious women actually exhibited higher respiration rate awareness.
      CONCLUSION: The results suggest that sexual concordance may be a distinct
      phenomenon from interoception and in need of its own explanation.

PMID- 23859299
TI  - Evaluation of a continuous glucose monitoring system compared with an in-house
      standard laboratory assay and a handheld point-of-care glucometer in critically
      ill neonatal foals.
AB  - OBJECTIVE: To evaluate the applicability and accuracy of a continuous glucose
      monitoring system (CGMS) in critically ill foals by comparing the performance of
      the CGMS, a point-of-care (POC) glucometer, and an in-house standard laboratory
      assay (SLA). DESIGN: Prospective study. SETTING: University teaching hospital.
      ANIMALS: Seven critically ill neonatal foals requiring intensive care.
      INTERVENTIONS: Foals were instrumented with a CGMS that measured interstitial
      glucose concentration every 5 minutes for the duration of 15-79 hours. Capillary
      and venous blood samples were taken every 4-6 hours for POC and SLA measurements,
      respectively. MEASUREMENTS AND MAIN RESULTS: Bland-Altman analysis showed a mean
      bias (95% limits of agreement) of -0.1 (-3.9 to 3.5) mmol/L for comparison of
      CGMS versus SLA, 0.06 (-3.9 to 4.0) mmol/L for comparison of CGMS versus POC
      glucometer, and -0.16 (-1.8 to 1.5) mmol/L for comparison of POC glucometer
      versus SLA. Percent agreement and weighted kappa for classification in
      hypoglycemia, normoglycemia, and hyperglycemia were 68.4% and 0.296 for CGMS
      versus SLA, 72.4% and 0.442 for CGMS versus POC glucometer, and 80.7% and 0.568
      for POC glucometer versus SLA. CONCLUSIONS: The CGMS may be helpful for
      monitoring a trend in interstitial glucose concentration in critically ill
      neonatal foals. However, considering the wide limits of agreement between
      methods, the CGMS should only be used as an adjunctive device to other, more
      accurate and readily available methods that are able to detect acute changes in
      glucose concentration. Its use is further limited by the relatively high costs of
      the sensors, the mandatory 2-hour initialization period, and the difficulties of
      keeping the transducer in place in an active foal. The POC glucometer used in
      this study is easy to use and proved to be sufficiently accurate for repeated,
      stall-sided glucose monitoring in neonatal foals.

PMID- 23859300
TI  - Targeting listeria monocytogenes rpoA and rpoD genes using peptide nucleic acids.
AB  - Treating intracellular pathogens remains a considerable medical challenge because
      of the inefficient intracellular delivery of antimicrobials and the frequent
      emergence of bacterial resistance to therapeutic agents deemed the drugs of last
      resort. We investigated the capability of antisense peptide nucleic acids (PNAs)
      conjugated to the (KFF)3K cell penetrating peptide to target RNA polymerase alpha
      subunit (rpoA) and RNA polymerase sigma 70 (rpoD) in the intracellular pathogen
      Listeria monocytogenes. The PNAs tested displayed a concentration dependent
      inhibition of L. monocytogenes growth in pure culture at the micromolar level and
      significantly reduced intracellular L. monocytogenes in infected cell culture and
      Caenorhabditis elegans whole animal model. In vitro, the combined PNAs treatment
      was synergistic resulting in a clearance of L. monocytogenes at 0.5* the
      individual PNA concentration. This study demonstrates the potential of anti-rpoA
      PNA as an antibacterial agent and will provide the basis for improving and
      developing these PNAs to better target intracellular pathogens like Listeria.
      This study also establishes C. elegans as a potential model for the screening of
      PNAs. 

PMID- 23859301
TI  - Inferring relationships between clinical mastitis, productivity and fertility: a
      recursive model application including genetics, farm associated herd management,
      and cow-specific antibiotic treatments.
AB  - A dataset of test-day records, fertility traits, and one health trait including
      1275 Brown Swiss cows kept in 46 small-scale organic farms was used to infer
      relationships among these traits based on recursive Gaussian-threshold models.
      Test-day records included milk yield (MY), protein percentage (PROT-%), fat
      percentage (FAT-%), somatic cell score (SCS), the ratio of FAT-% to PROT-% (FPR),
      lactose percentage (LAC-%), and milk urea nitrogen (MUN). Female fertility traits
      were defined as the interval from calving to first insemination (CTFS) and
      success of a first insemination (SFI), and the health trait was clinical mastitis
      (CM). First, a tri-trait model was used which postulated the recursive effect of
      a test-day observation in the early period of lactation on liability to CM (LCM),
      and further the recursive effect of LCM on the following test-day observation.
      For CM and female fertility traits, a bi-trait recursive Gaussian-threshold model
      was employed to estimate the effects from CM to CTFS and from CM on SFI. The
      recursive effects from CTFS and SFI onto CM were not relevant, because CM was
      recorded prior to the measurements for CTFS and SFI. Results show that the
      posterior heritability for LCM was 0.05, and for all other traits, heritability
      estimates were in reasonable ranges, each with a small posterior SD. Lowest
      heritability estimates were obtained for female reproduction traits, i.e.
      h(2)=0.02 for SFI, and h(2)~0 for CTFS. Posterior estimates of genetic
      correlations between LCM and production traits (MY and MUN), and between LCM and
      somatic cell score (SCS), were large and positive (0.56-0.68). Results confirm
      the genetic antagonism between MY and LCM, and the suitability of SCS as an
      indicator trait for CM. Structural equation coefficients describe the impact of
      one trait on a second trait on the phenotypic pathway. Higher values for FAT-%
      and FPR were associated with a higher LCM. The rate of change in FAT-% and in FPR
      in the ongoing lactation with respect to the previous LCM was close to zero.
      Estimated recursive effects between SCS and CM were positive, implying strong
      phenotypic impacts between both traits. Structural equation coefficients
      explained a detrimental impact of CM on female fertility traits CTFS and SFI. The
      cow-specific CM treatment had no significant impact on performance traits in the
      ongoing lactation. For most treatments, beta-lactam-antibiotics were used, but
      test-day SCS and production traits after the beta-lactam-treatment were
      comparable to those after other antibiotic as well as homeopathic treatments.

PMID- 23859302
TI  - One size fits all: Eurasian lynx females share a common optimal litter size.
AB  - Lack proposed that the average clutch size of altricial species should be
      determined by the average maximum number of young the parents can raise such that
      all females in a given population should share a common optimal clutch size.
      Support for this model remains equivocal and recent studies have suggested that
      intra-population variation in clutch size is adaptive because each female has its
      own optimal clutch size associated with its intrinsic ability to raise offspring.
      Although Lack litter size and condition-dependent litter size are presented as
      two competing models, both are based on the concept of individual optimization.
      We propose a unified optimal litter size model (called 'adaptive litter size')
      and identify a set of conditions under which a common vs. a state-dependent
      optimal litter size should be observed. We test whether females of Eurasian lynx
      (Lynx lynx) have a common optimal litter size, or whether they adjust their
      litter size according to their state. We used a detailed individual-based data
      set collected from contrasting populations of Eurasian lynx in Scandinavia.
      Observed reproductive patterns in female lynx provide strong support for the
      existence of a common optimal litter size. Litter size did not vary according to
      female body mass or reproductive category, or among contrasted populations and
      years. A litter size of 2 was associated with a higher fitness than both smaller
      and larger litters, and thus corresponded to the 'adaptive litter size' for
      female lynx. We suggest that the reproductive pattern of female lynx might
      correspond to a risk avoidance tactic common to all individuals, which has
      evolved in response to strong environmental constraints generated by a highly
      unpredictable food supply during lactation.

PMID- 23859304
TI  - Surgical-site infection after abdominal wall closure with triclosan-impregnated
      polydioxanone sutures: results of a randomized clinical pathway facilitated trial
      (NCT00998907).
AB  - BACKGROUND: Wound infections after abdominal surgery are still frequent types of
      nosocomial infections. Suture materials might serve as a vehicle for mechanical
      transport of bacteria into the surgical wound. To prevent the contamination of
      suture material in surgical wounds, triclosan-coated suture materials with
      antibacterial activity was developed. We here report a prospective randomized
      pathway controlled trial investigating the effect of triclosan impregnation of
      polydioxanone sutures used for abdominal wall closure on the rate of surgical
      site infections. PATIENTS AND METHODS: A total of 856 patients included in this
      trial underwent a standardized clinical pathway documented abdominal wall closure
      after abdominal surgery. Patients were randomized to have the fascia closed with
      either a 2-0 polydioxanone loop or a triclosan impregnated 2-0 polydioxanone
      loop. The primary outcome was the number of wound infections. Risk factors for
      poor wound healing were collected prospectively to compare the two groups.
      RESULTS: When a PDS loop suture for abdominal wall closure was used, 42 (11.3%)
      patients with wound infections were detected. The number of patients with wound
      infections decreased significantly to 31 when the PDS plus for abdominal wall
      closure was used (6.4%, P < .05). Other risk factors for the development of side
      infections were comparably in the two groups. CONCLUSION: This clinical pathway
      facilitated trial shows that triclosan impregnation of a 2-0 polydioxanone
      closing suture can decrease wound infections in patients having a laparotomy for
      general and abdominal vascular procedures.

PMID- 23859303
TI  - The efficacy and safety of fixed-dose combination of amlodipine/benazepril in
      Chinese essential hypertensive patients not adequately controlled with benazepril
      monotherapy: a multicenter, randomized, double-blind, double-dummy, parallel
      group clinical trial.
AB  - This double-blind, double-dummy clinical trial evaluated the efficacy and safety
      of two strengths of fixed-dose combination of amlodipine/benazepril in Chinese
      hypertensive patients not adequately controlled with benazepril. Of 442 patients
      who received treatment with benazepril 10 mg for 4 weeks, 341 patients failed to
      achieve to diastolic blood pressure (DBP) <90 mmHg. These non-responders were
      randomized to receive amlodipine/benazepril 2.5/10 mg, or amlodipine/benazepril
      5/10 mg, or benazepril 10 mg for 8 weeks. BP reductions with
      amodipinel/benazepril 2.5/10 mg (15.2/11.8 mmHg) or amlodipine/benazepril 5/10 mg
      (15.4/12.4 mmHg) were significantly greater than that with benazepril 10 mg
      (9.88/9.46 mmHg) at study end (p < 0.01, combination versus benazepril). BP
      control rate was 83.8% with amlodipine/benazepril 2.5/10 mg, 80.2% with
      amlodipine/benazepril 5/10 mg, 64.9% with benazepril 10 mg at study end (p <
      0.01, combination versus benazepril). Three groups were generally well tolerated.
      Our study indicated that amlodipine/benazepril fixed-dose combination offered
      significant additional BP reductions and BP control rate compared with the
      continuation of benazepril monotherapy. No significant differences were observed
      in both BP reductions and BP control rate between amlodipine/benazepril 2.5/10 mg
      and amlodipine/benazepril 5/10 mg.

PMID- 23859305
TI  - Acidic lactate sequentially induced lymphogenesis, phlebogenesis, and
      arteriogenesis (ALPHA) hypothesis: Lactate-triggered glycolytic vasculogenesis
      that occurs in normoxia or hypoxia and complements the traditional concept of
      hypoxia-based vasculogenesis.
AB  - Our hypothesis, ALPHA (Acidic Lactate sequentially induced Lymphogenesis,
      PHlebogenesis, and Arteriogenesis) proposes that lactate triggers vasculogenesis
      to manage lactate levels and complements the traditional vasculogenesis
      hypothesis. The teleologic basis for glycolytic vasculogenesis is primariy to
      produce drainage vessels, initially lymphatics but subsequently veins. 

PMID- 23859306
TI  - Guanine nucleotide exchange factor-H1 signaling is involved in lipopolysaccharide
      induced endothelial barrier dysfunction.
AB  - BACKGROUND: Gram-negative bacterial lipopolysaccharide (LPS) leads to the
      pathologic increase of vascular leakage under septic conditions. However, the
      mechanisms behind LPS-induced vascular hyperpermeability remain incompletely
      understood. In this study, we tested hypothesis that guanine nucleotide exchange
      factor-H1 (GEF-H1) signaling might be a key pathway involved in endothelial cells
      (ECs) barrier dysfunction. METHODS: The roles of GEF-H1 signaling pathway in LPS
      induced ECs barrier dysfunction were accessed by Evans blue dye-labeled albumin
      (EB-albumin) leak across the human umbilical vein EC (HUVEC) monolayers and
      Western blot assays. Furthermore, the effect of GEF-H1 signaling on LPS-induced
      alteration of cytoskeletal proteins and disruption of cell-cell junctions were
      analyzed by immunofluorescent analysis and Western blot assays, respectively.
      RESULTS: We found that LPS could rapidly activated GEF-H1/RhoA/Rho-associated
      protein kinase (ROCK) signaling pathway in ECs. The LPS-mediated increase in EB
      albumin flux across human HUVECs monolayers could be prevented by GEF-H1
      depletion or ROCK inactivation. ECs permeability is controlled by actin filaments
      and cell-cell contact protein complexes. Actin stress fiber formation and/or cell
      cell contact proteins loss cause vascular barrier disruption. Here, GEF-H1
      knockdown or ROCK inactivation both not only significantly inhibited LPS-induced
      actin stress fiber formation, phosphorylation of myosin light chain, and myosin
      associated phosphatase type 1, but also suppressed LPS-induced loss of occludin,
      claudin-1, and vascular endothelial (VE)-cadherin in ECs, which suggested that
      LPS-induced stress fiber formation and cell-cell junctions disruption were
      closely associated with GEF-H1/RhoA/ROCK signaling activation. CONCLUSION: Our
      findings indicate that GEF-H1/RhoA/ROCK pathway in ECs plays an important role in
      LPS-mediated alteration of cell morphology and disruption of cell-cell junctions,
      consequently regulate LPS-induced vascular permeability dysfunction.

PMID- 23859307
TI  - Efficacy of laparoscopic radiofrequency ablation for the treatment of patients
      with small solitary colorectal liver metastasis.
AB  - BACKGROUND: Although radiofrequency ablation (RFA) has been incorporated to the
      treatment algorithm of patients with unresectable colorectal liver metastasis
      (CLM), its utility in patients with resectable disease has not been well studied.
      The aims of this study were to define the clinical profile of patients with a
      solitary CLM who underwent laparoscopic RFA and to analyze their oncologic
      outcomes. METHODS: Between 2000 and 2011, 44 patients underwent laparoscopic RFA
      and 60 patients resection of solitary CLM <=3 cm. Data were analyzed from a
      prospectively maintained institutional review board-approved database using
      Student's t test, Chi-square, and Kaplan-Meier tests. RESULTS: The indications
      for RFA were patient decision in 61% (n = 27), comorbidities in 34% (n = 15), and
      intraoperative findings in 5% (n = 2). In comparison with the resection group,
      RFA patients had a greater American Society of Anesthesiologists score (3.0 +/-
      0.1 vs 2.6 +/- 0.1, respectively; P = .002), more frequent incidence of
      cardiopulmonary comorbidities (60% vs 38%, respectively; P = .045), and tumors
      located deeper in the liver parenchyma (39% vs 12%) that would have required a
      formal lobectomy. The 2 groups were otherwise similar for age, gender,
      carcinoembrradyogenic antigen, synchronous versus metachronous presentation of
      CLM, tumor size, and tumor and nodal status of primary colorectal cancer. The
      local recurrence rate was 18% after RFA and 4% after resection (P = .012). The
      overall Kaplan-Meier, cancer-specific, 5-year survival was 47% for RFA and 57%
      for resection (P = .464). Median disease-free survival was 25 months after RFA
      and 22 months after resection (P = .973). CONCLUSION: Our results suggest that
      laparoscopic RFA might spare a number of patients at greater risk with a small
      solitary CLM the risk of morbidity from a formal liver resection. Furthermore,
      laparoscopic RFA might also be acceptable as the first line of therapy for
      patients with tumors that otherwise would have required a formal lobectomy or
      open resection. Nevertheless, the local recurrence rate of RFA should be kept in
      mind and the patients followed closely to treat failures promptly.

PMID- 23859308
TI  - Triangulating stapling technique for esophagogastrostomy after minimally invasive
      esophagectomy.
AB  - BACKGROUND: The triangulating stapling technique is one of the reconstruction
      methods used that provides favorable surgical outcomes in several areas of the
      digestive tract. However, the results in the cervical esophagogastric anastomosis
      are not well documented. METHODS: Using a prospectively maintained comprehensive
      database, we reviewed the surgical results of 160 consecutive patients who
      underwent minimally invasive esophagectomy followed by cervical triangulating
      stapling esophagogastrostomy during 2 periods from May 2002 to May 2012 so as to
      determine the efficacy of the triangulating stapling technique using 2 different
      types of stapling devices. RESULTS: The rates of anastomotic leakage and
      stricture in this series were low (1% and 15%, respectively). The rate of
      anastomotic stricture was significantly reduced when a linear stapler with a
      cutting knife was used (9%). A logistic regression analysis showed a reduction of
      anastomotic stricture to be significantly associated with the use of only a
      linear stapler with a cutting knife. CONCLUSION: Cervical esophagogastric
      anastomosis by the triangulating stapling technique is safe and feasible. We
      consider a linear stapling device equipped with a cutting knife to be more
      suitable for performing the triangulating stapling technique.

PMID- 23859309
TI  - C-reactive protein inhibits lymphangiogenesis and resultant lymph node metastasis
      of squamous cell carcinoma in mice.
AB  - BACKGROUND: Lymph node involvement is the most important prognostic factor in
      many solid cancers. Recently, we found that patients with esophageal and lung
      cancer carrying the C-reactive protein (CRP) 1846T/T genotype, which is
      associated with lower serum CRP levels, are more likely to have lymph node
      metastasis. We hypothesized that host CRP directly inhibits lymph node
      metastasis. METHODS: We inoculated NR-S1M metastatic cells subcutaneously into
      the backs of C3H/HeN mice. Concurrently, 1 MUg of recombinant mouse CRP or
      phosphate-buffered saline was injected subcutaneously every 3 days for 5 weeks,
      after which the mice were killed for evaluation. We evaluated lymph node
      metastasis and lymphangiogenesis in the implanted tumor by using
      immunohistochemical analysis with anti-pancytokeratin and antilymphatic vessel
      endothelial hyaluronan receptor-1 antibodies. RESULTS: There was no substantial
      difference in tumor size between the 2 groups but the lymph nodes were smaller in
      the CRP group than the control group (P < .044). Immunohistochemical analysis
      confirmed inguinal lymph node metastasis in 70% (14/20) of control mice, but in
      only 30% (3/10) of mice in the CRP group. Moreover, the metastatic area within
      lymph nodes was less in the CRP group (P < .042) and tumoral lymphangiogenesis
      was decreased in the CRP group (P < .037). CONCLUSION: CRP appears to inhibit
      tumoral lymphangiogenesis and lymph node metastasis in mice. These findings
      suggest that by inhibiting lymph node metastasis, CPR may have therapeutic
      potential for use against cancer.

PMID- 23859310
TI  - Gold(I) or silver catalyzed synthesis of alpha-indolylacrylates.
AB  - Methyl 2-acetamidoacrylate reacted with various 2-substituted indoles in the
      presence of catalytic amounts of AgSbF6 or AuPPh3NTf2 to provide the
      corresponding methyl 2-(2-substituted-1H-indol-3-yl)acrylates. 

PMID- 23859311
TI  - Efficiency of cytogenetic methods in detecting a chromosome rearrangement induced
      by ionizing radiation in a cultivated chili pepper line (Capsicum baccatum var.
      pendulum--Solanaceae).
AB  - PURPOSE: To locate transient chromosome aberrations on a selected pepper cultivar
      and determine the tracing efficiency of different cytogenetic methods. MATERIALS
      AND METHODS: Seeds from Capsicum baccatum var. pendulum cultivar 'Cayenne' were
      treated with an acute dose of X-rays (300 Gy) and chromosome aberrations were
      analysed by different cytogenetic methods [Feulgen, silver staining for nucleolus
      organizer regions (silver positive nucleolus organizing regions or AgNOR),
      fluorescent banding, fluorescence in situ hybridization (FISH) and meiotic
      analysis]. RESULTS: A rearranged chromosome carrying two nucleolus organizing
      regions (NOR) induced by ionizing radiation was detected in the cultivar, with
      the occurrence of a small reciprocal exchange between a chromosome of pair no. 1
      and another chromosome of pair no. 3, both carrying active NOR in short arms and
      associated chromomycin A positive/diamidino-phenylindole negative (CMA+/DAPI-)
      heterochromatin. Meiotic analysis showed a quadrivalent configuration, confirming
      a reciprocal translocation between two chromosomes. CONCLUSIONS: The use of X
      rays in Capsicum allowed us to develop and identify a pepper line with structural
      rearrangements between two NOR-carrying chromosomes. We postulate that all the
      cytological techniques employed in this research were efficient in the search for
      chromosome aberrations. Particularly, Feulgen and AgNOR were the most suitable in
      those cases of transient rearrangements, whereas fluorescent banding and FISH
      were appropriate for intransitive ones.

PMID- 23859312
TI  - Excellent liver retransplantation outcomes in hepatitis C-infected recipients.
AB  - Survival outcomes for liver retransplantation (LRTx) after graft loss in HCV
      patients (HCV-LRTx) are generally considered inferior to those after non-HCV
      LRTx. Between January 1, 2005 and June 30, 2011, our center performed 663 LTx,
      including 116 (17.5%) LRTx, 41 (35.3%) of which were more than 90 d after the
      LTx. Twenty-nine (70.7%) LRTx were performed in HCV antibody-positive
      individuals. We compared patient demographics, baseline characteristics and
      outcomes of our HCV-LRTx group with the HCV-LRTx patients from the most recent
      OPTN database covering the same time period. Our Kaplan-Meier HCV-LRTx one-,
      three-, and five-yr HCV-LRTx patient survival rates were 86.2%, 79.0%, and 72.4%,
      respectively compared with the OPTN one-, three-, and five-yr HCV-LRTx survival
      rates of 73.3%, 59.0%, and 51.3% respectively. Likewise, our graft survival rates
      were higher than OPTN rates at all time points studied. We performed a higher
      percentage of HCV-LRTx as simultaneous liver/kidney transplants (SLK) (37.9% vs.
      21.8%) and recorded shorter warm (30 +/- 4 vs. 45 +/- 23 min) and cold ischemic
      times (5:44 +/- 1:53 vs. 7:36 +/- 3:12 h:min). CONCLUSION: In our experience, HCV
      LRTx patient and graft survival rates are comparable to LTx survival rates and
      are higher than the rates described by OPTN.

PMID- 23859313
TI  - A comparative study of count models: application to pedestrian-vehicle crashes
      along Malaysia federal roads.
AB  - OBJECTIVES: The objective of this study was to examine the effects of various
      roadway characteristics on the incidence of pedestrian-vehicle crashes by
      developing a set of crash prediction models on 543 km of Malaysia federal roads
      over a 4-year time span between 2007 and 2010. METHODS: Four count models
      including the Poisson, negative binomial (NB), hurdle Poisson (HP), and hurdle
      negative binomial (HNB) models were developed and compared to model the number of
      pedestrian crashes. RESULTS AND CONCLUSIONS: The results indicated the presence
      of overdispersion in the pedestrian crashes (PCs) and showed that it is due to
      excess zero rather than variability in the crash data. To handle the issue, the
      hurdle Poisson model was found to be the best model among the considered models
      in terms of comparative measures. Moreover, the variables average daily traffic,
      heavy vehicle traffic, speed limit, land use, and area type were significantly
      associated with PCs.

PMID- 23859314
TI  - Evidence for adaptive phenotypic differentiation in Baltic Sea sticklebacks.
AB  - The evidence for adaptive phenotypic differentiation in mobile marine species
      remains scarce, partly due to the difficulty of obtaining quantitative genetic
      data to demonstrate the genetic basis of the observed phenotypic differentiation.
      Using a combination of phenotypic and molecular genetic approaches, we elucidated
      the relative roles of natural selection and genetic drift in explaining lateral
      plate number differentiation in threespine sticklebacks (Gasterosteus aculeatus)
      across the entire Baltic Sea basin (approximately 392 000 km(2) ). We found that
      phenotypic differentiation (PST  = 0.213) in plate number exceeded that in
      neutral markers (FST  = 0.008), suggesting an adaptive basis for the observed
      differentiation. Because a close correspondence was found between plate phenotype
      and genotype at a quantitative trait loci (QTL; STN381) tightly linked to the
      gene (Ectodysplasin) underlying plate variation, the evidence for adaptive
      differentiation was confirmed by comparison of FST at the QTL (FSTQ  = 0.089)
      with FST at neutral marker loci. Hence, the results provide a comprehensive
      demonstration of adaptive phenotypic differentiation in a high-gene-flow marine
      environment with direct, rather than inferred, verification for the genetic basis
      of this differentiation. In general, the results illustrate the utility of PST 
      FST -FSTQ comparisons in uncovering footprints of natural selection and evolution
      and add to the growing evidence for adaptive genetic differentiation in high-gene
      flow marine environments, including that of the relatively young Baltic Sea. 

PMID- 23859315
TI  - In response to: Regeneration of chronic tympanic membrane perforation using an
      EGF-releasing chitosan patch.

PMID- 23859316
TI  - [The guidelines interpretation for diagnosis and treatment of severe acute
      pancreatitis].

PMID- 23859317
TI  - [The current status and progress on the treatment of spine and spinal cord
      disorders].

PMID- 23859318
TI  - [Individualized treatment of the atlantoaxial dislocation in craniovertebral
      junction abnormalities].
AB  - OBJECTIVES: To analyze the clinical characteristics of the atlantoaxial
      dislocation (AAD) in craniovertebral junction (CVJ) abnormalities and to study
      the setup of its surgery strategy. METHODS: From April 2009 to November 2011, 56
      patients of AAD and CVJ abnormalities including 22 male and 34 female patients
      who had received surgery were analyzed. There were 2 cases of reducible AAD and
      54 cases of irreducible AAD. The age of the patients ranged from 9 to 56 years
      (mean 34 years). Among them, 14 cases achieved reduction/partial reduction via
      direct posterior fixation, 41 cases had transoral anterior deconpression and
      occipito-cervical/C1-C2 fusion and 1 case had the posterior odontoidectomy and
      spinal fusion. RESULTS: Fifty-three cases had a follow-up between 6 months and 36
      months (mean 20 months) and 3 cases lost follow-up (had improvement at
      discharge). Seven cases had complications as follows: 1 case had irreversible
      spinal cord injury and muscle weakness of extremities, 2 cases had cerebrospinal
      leak, 2 cases had pulmonary infection, 1 case had local granuloma hyperplasia and
      1 case had delayed healing of the incision. The later 6 cases all got recovery
      after reasonable treatments. The grades of Nurick at last follow-up were as
      follows: 6 cases (11.3%) improved by 3 grades, 30 cases (56.6%) improved by 2
      grades, 13 cases (24.5%) improved by 1 grade, 3 cases (5.7%) without change, 1
      case (1.9%) get worse. CONCLUSIONS: Reducible AAD could achieve direct reduction
      and fixation via posterior pathways. Irreducible AAD needs individualized
      treatment. To choose the direct reduction and fixation or transoral
      odontoidectomy and posterior fixation and fusion should consider the pathogenetic
      condition, the image data and personal clinical experience.

PMID- 23859319
TI  - [An analysis of surgical outcome and influencing factors in patients of
      congenital basilar invagination with atlantal-axial dislocation: report of 120
      cases].
AB  - OBJECTIVE: To investigate the surgical outcome and its influencing factors in
      patients of congenital basilar invagination (BI) with atlanto-axial dislocation
      (AAD). METHODS: From May 2004 to August 2010, 120 patients who had BI with AAD
      were surgically treated with direct posterior intraoperative distraction
      reduction and fixation technique, 93 patients were successfully followed up by
      means of questionnaire survey, telephone and clinical evaluation. Pre- and
      postoperative dynamic cervical X-rays, computed tomographic scans, 3-dimentional
      reconstruction views and magnetic resonance imaging were performed. Pre- and
      postoperative Japanese Orthopaedic Association (JOA) score, distance between
      odontoid tip and Chamberlain's line and atlantodental interval were measured to
      evaluate the surgical result. Statistical analysis was performed by means of
      paired t test and Pearson Correlation analysis. RESULTS: There were 93 cases were
      followed up for 24-99 months with an average of 46.5 months. Until the final
      follow-up, clinical symptoms were improved in 79 patients (84.9%), and were
      stable in 7 patients (7.5%) and deteriorated in 4 patients (4.3%). Three patients
      died postoperatively (3.2%). Patients without intramedullary signal intensity
      change (ISIC) had better surgical outcome. Patients with compression from
      anterior odontoid tip and posterior bone margin of occipital foramen had the
      worst surgical outcome (F = 3.987, P < 0.01). Overall, good decompression and
      bone fusion were shown on postoperative image in 87 patients (93.5%). There were
      3 deaths in this series because of basilar artery thrombosis, posterior fossa
      hematoma and unknown reasons each. CONCLUSIONS: The direct posterior
      intraoperative distraction-reduction and fixation technique is an effective
      simple and safe method for the treatment of BI with AAD. Anterior compression
      from odontoid tip and posterior compression from bone margin of occipital foramen
      atlantal posterior arch play important roles in its developing mechanism. ISIC on
      MRI is a predictive factor for the worse surgical outcome.

PMID- 23859320
TI  - [Outcome of microsurgical decompression combined with cervical artificial disc
      replacement].
AB  - OBJECTIVE: To study the microsurgical decompression combined with cervical
      artificial disc replacement clinical efficacy for the treatment of cervical
      spondylosis. METHODS: From January 2006 to November 2011, 21 cases of cervical
      spondylosis, totally 23 intervertebral spaces, were under the microscope disc
      decompression and cervical artificial disc replacement. There were 11 male and 10
      female patients; aged from 28 to 60 years, with an average of 46.3 years. The
      diagnosis included 5 cases of nerve root type cervical spondylosis and 16 cases
      of cervical spondylotic myelopathy. Application of Bryan prosthesis treatment of
      9 patients, a total of 10 intervertebral spaces; ProDisc-C prosthesis to treat 12
      patients, a total of 13 intervertebral space. Following-up Japanese Orthopedic
      Association (JOA), neck disability index (NDI) and visual analogue scale (VAS)
      scores were recorded and compared with pre-operative scores by the paired t-test.
      RESULTS: The patients were followed up for 6 to 74 months, with an average of
      27.7 months. Although a patient with spinal bony stenosis symptom improved, but
      not satisfied, and after the posterior decompression, who had a better prognosis.
      The remaining patients during follow-up symptoms were obvious improved, and the
      replacement segments were stable. There was no prosthesis subsidence and
      significantly offset. In 1 month post-operation and last follow-up compared with
      pre-operative scores, JOA (t = 9.195 and 17.070), NDI (t = 7.193 and 14.062) and
      VAS (t = 14.851 and 16.133) scores were significantly different (P < 0.05); and 1
      month post-operation compared with last follow-up, JOA (t = 5.916), NDI (t =
      7.722) and VAS (t = 4.564) scores were significantly different (P < 0.05).
      CONCLUSIONS: Cervical artificial disc replacement combined with microscopic
      decompression surgery can completely remove the oppression of nerve tissue caused
      by pressure, and the efficacy is more secure.

PMID- 23859321
TI  - [Feasibility and efficiency of embolization of spinal dural arteriovenous
      fistula].
AB  - OBJECTIVE: To evaluate the feasibility and efficiency of embolization of spinal
      dural arteriovenous fistula (SDAVF). METHODS: From December 2010 to May 2012,
      there were 104 cases of SDAVF were treated, and 26 cases were selected to be
      treated with embolization. The inclusion criteria was as follows: (1) No anterior
      or posterior spinal artery originated from the fistula segment; (2) The segmental
      artery can be catheterized with guiding or micro catheter; (3) High flow in
      fistula; (4) Patient's situation was not suitable for surgery or general
      anesthesia. Among 26 cases, there were 22 male and 4 female patients, the average
      age was 55.9 years (ranged from 34 to 81 years). The locations of SDAVF were 10
      cases in thoracic, 9 in lumbar and 7 in sacral segment. The main symptoms were
      progressive numbness and weakness in both lower extremities, most cases
      accompanied with difficulties in urination and defecation. The average history
      was 17.1 months (from 1 to 156 months). ONYX-18 liquid embolic agent or Glubran-2
      surgical glue were used as embolic material. The patients not cured with
      embolization were treated with surgery in the following 1 - 2 weeks. Follow-up
      evaluation was done with MRI after 3 months and DSA after 6 months, besides
      physical examination. RESULTS: Fifteen from 26 cases achieved immediate
      angiographic cure results: 14 in 20 cases which embolized with ONYX-18; only 1 in
      6 cases with Glubran-2. Three in 10 cases of thoracic SDAVF and 12 in 16 cases of
      lumbar/sacral SDAVF were cured with embolization. Partially embolized cases were
      treated with surgical obliteration of drainage veins within 2 weeks. Cured
      patients experienced immediate improvement after embolization and kept getting
      better in the follow-up. All the patients had MRI follow-up after 3 months and
      DSA follow-up after 6 months. In 6 month's follow-up, MRI showed the edema and
      flow void signal in the spinal cord disappeared. DSA showed no fistula recurrence
      or remnant. There was no deterioration case in all of the embolized cases.
      CONCLUSIONS: Particular SDAVF is suitable for embolization with ONYX-18. Most
      lesions located in lumbar and sacral segment are good indications for
      embolization.

PMID- 23859322
TI  - [Pancreatic acinar cell carcinoma: diagnostic and surgical treatment strategy].
AB  - OBJECTIVE: To investigate the clinical features, diagnostic and therapeutic
      strategy of pancreatic acinar cell carcinoma. METHODS: The data of pancreatic
      acinar cell carcinoma patients who underwent surgical operations from January
      2002 to January 2012 were retrospectively reviewed. RESULTS: Six cases of
      pancreatic acinar cell carcinoma, identified with pathology were collected,
      including 3 males and 3 females with the average of 47.8 yeas old. Upper
      abdominal pain was present in 5 cases, weight loss was present in 4 cases with
      the average of 12.5 kg. Other symptoms included nausea/vomiting, back pain and
      obstructive jaundice. The serum CA19-9 and CA24-2 level were significantly
      elevated in 2 cases. CT scan, MRI and DSA were the main imaging methods to
      diagnose this disease. However, no case was diagnosed as pancreatic acinar cell
      carcinoma before operation. All cases were confirmed by the pathological
      examination. Relatively high rates of surgical resection, long operative time,
      more blood loss and combined multi-organ resection were the characteristics of
      this disease's operative surgical procedures. The average period of postoperative
      follow-up process was 60 months, and the mean survival time was (32 +/- 8)
      months. CONCLUSIONS: The clinical features and biological behavior of pancreatic
      acinar cell carcinoma are different from those of ductal adenocarcinoma, while
      the relatively specific clinical manifestations and imaging changes will be
      helpful for qualitative diagnosis before operation. As it has high rate of
      resection and better prognosis, more radical surgical strategies should be
      carried out for patients of this disease.

PMID- 23859323
TI  - [The diagnosis, treatment and prognosis evaluation of gastric small cell
      carcinoma: analysis of 41 cases].
AB  - OBJECTIVE: To summarize and analyze the clinical feature, therapeutic methods and
      prognosis of gastric small cell carcinoma (SCC). METHODS: The clinical and
      pathological data of 41 patients diagnosed of gastric SCC were analyzed in this
      research. Also, the factors which may potentially affect the patients' survival
      outcome were evaluated. There were 35 male and 6 female patients. The age at
      diagnosis was 39-84 years, median age was 62 years. The 31 cases (75.6%) of
      gastric SCC patients were involved in the upper third of the stomach, 3 cases
      (7.3%) in the middle, 7 cases (17.1%) in the lower third. RESULTS: The time from
      the event of symptoms to final confirmation was 1 to 13 months, the median time
      was 3 months. The longest diameter of tumors was from 2.5 to 15.0 cm, the average
      was 6.5 cm. The 38 cases (92.7%) chosed surgery as the first treatment, among
      which 25 cases (61.0%) were performed radical tumor resection, 13 cases (31.7%)
      went through palliative resection, and 3 cases (7.3%) just employed chemotherapy.
      The initial II, III, IV stage were 2, 31 and 8 cases, respectively. The overall
      median survival time was 19 months, median disease free survival time was 11
      months, 1-, 2-, 5-years survival rates were 70.7%, 46.3% and 36.6%, respectively.
      In univariate survival analysis, the tumor size (chi2 = 5.565), change of the
      body weight (chi2 = 3.688), type of operation (chi2 = 11.747) and relapse or not
      (chi2 = 17.966) were obviously correlaed with the prognosis (P < 0.05).
      CONCLUSIONS: Gastric SCC is a rare disease of the gastrointestinal tract, the
      misdiagnosis rate is high, and the prognosis is dismal. Muti-modality management,
      with radical surgical resection of the primary lesion followed by standard
      adjuvant-chemotherapy, affords better local disease control and a better survival
      outcome.

PMID- 23859324
TI  - [The prognostic analysis of tumor size in T4a stage gastric cancer].
AB  - OBJECTIVE: To investigate the impact of tumor size in the prognosis of T4a stage
      gastric cancer. METHODS: The best cut-off point depending on tumor size was
      selected by Kaplan-Meier. Compare cliniclopathological characteristics between
      small size gastric cancer (SSG) and large size gastric cancer (LSG). Univariate
      analysis was done by Log-rank test and multivariate analysis was performed using
      the Cox proportional hazard regression model. The independent prognostic factors
      of patients were performed subgroup analysis. RESULTS: Eight centimetre was the
      optimal cut-off of tumor size for T4a stage gastric cancer. There were
      significantly differences between SSG and LSG in tumor location (chi2 = 15.695),
      histological grade (chi2 = 4.393), macroscopic type (chi2 = 5.629) and early
      recurrence (chi2 = 4.292). Univariate analysis showed age (chi2 = 4.463), tumor
      size (chi2 = 9.057), macroscopic type (chi2 = 6.679), histological grade (chi2 =
      5.122), location of tumor (chi2 = 8.707) and N stage (chi2 = 132.954) are related
      to survival (P < 0.05). Among them, tumor size (HR = 1.339), histological grade
      (HR = 1.169) and N stage (HR = 1.876) were independent risk factor for survival
      (P = 0.05). For SSG, N stage (HR = 2.014) and histological grade (HR = 1.192)
      were independent risk factor for survival (P = 0.05), and for LSG, N stage (HR =
      1.876) was independent risk factor for survival (P = 0.000). Further stratified
      analysis indicated that the 5-year survival rate of LSG is significantly lower
      than that of SSG in T4a stage patients of gastric cancer without lymph nodes
      metastasis or poorly differentiated (HR = 0.182 and 0.653, P < 0.01).
      CONCLUSIONS: Tumor size is an independent prognostic factor in patients of T4a
      stage gastric cancer. Tumor size cut-off point of 8 cm can exert significant
      impact on the prognosis of T4a stage gastric cancer without lymph nodes
      metastasis or poorly differentiated.

PMID- 23859325
TI  - [The significance of No.13 lymph node dissection in D2 gastrectomy for lower
      third advanced gastric cancer].
AB  - OBJECTIVE: To evaluate the feasibility and necessity of No.13 lymph node
      dissection in D2 radical gastrectomy for lower-third advanced gastric cancer
      (AGC). METHODS: Data of 379 cases who were diagnosed as TNM II-III stage AGC were
      collected from January 2001 to June 2007. One hundred cases who undergone No.13
      lymph node dissection during D2 gastrectomy for lower-third AGC were selected as
      study group. Other 279 cases (control group) received only D2 gastrectomy. The
      differences in clinicopathologic and intraoperative and postoperative parameters
      and 5-years survival rate were compared using the SPSS 17.0 software. RESULTS:
      There were no significant differences between the two groups in patients' gender,
      age, tumor size, histologic type, Borrmann type, duodenum invasion, tumor depth,
      lymph node metastasis, TNM classification, operative time, blood loss and the
      incidence of postoperative complications (P > 0.05). In the study group, there
      were 9 patients with positive No. 13 lymph node, and its 5-year survival rate
      (46.0%) was higher than the control group (36.5%, chi2 = 4.452, P < 0.05). The
      Univariate analysis showed that age (chi2 = 7.539), No.13 lymph node dissection
      (chi2 = 4.452), tumor size (chi2 = 7.100), duodenum invasion (chi2 = 9.106),
      tumor depth (chi2 = 7.428), lymph node metastasis (chi2 = 45.046), TNM
      classification (chi2 = 57.008) are associated with prognosis of lower-third AGC
      (P < 0.05). Multivariate analysis identified age (HR = 0.500, 95% CI: 0.343 -
      0.730), tumor size (HR = 0.545, 95%CI: 0.339 - 0.876), duodenum invasion (HR =
      5.821, 95%CI: 2.326 - 14.572), and tumor depth (T4: HR = 2.087, 95% CI: 1.283 -
      3.394) as independent prognostic factors (P < 0.05). CONCLUSION: No. 13 lymph
      node dissection for TNM II-III stage lower-third advanced gastric cancer is
      feasible and necessary.

PMID- 23859326
TI  - [Combined iliac artery stenting and open femoral endarterectomy in the treatment
      of multi-level iliac and common femoral occlusive disease].
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of hybrid procedure for the
      treatment of multi-level iliac and common femoral occlusive disease. METHODS:
      From January 2008 to June 2011, 36 lower limbs with sever iliac and common
      femoral occlusive diseases were treated by iliac artery stenting combined with
      open femoral endarterectomy. The mean age of the whole study population was 65
      years (range 49 to 87 years) with a male predominance (26 males, 72.2%). The
      early clinical results were determined by ankle brachial index and intermittent
      claudication distance. Patency analyses were performed using Kaplan-Meier life
      tables. Univariate and multivariate analysis were used to assess the influence of
      various risk factors on primary patency. RESULTS: All lower limbs underwent
      successful hybrid surgical and endovascular therapy. Clinical improvement was
      seen in 94.4% of patients. The mean duration of follow-up was 24.2 months,
      overall, the primary patency rates, primary assisted patency rates and second
      patency rates were 72.2%, 83.3% and 94.4% respectively. The primary patency rate
      for intermittent claudication was significantly higher than that for critical
      limb ischemia (P = 0.041, 0.012). Cox regression analysis did not reveal any
      independent predictor of primary patency. CONCLUSION: Hybrid procedures provided
      an effective treatment management of multilevel iliac-femoral arterial occlusive
      disease.

PMID- 23859327
TI  - [Analysis of cause and treatment of acute limb ischemia complicated in peripheral
      endovascular interventions].
AB  - OBJECTIVE: To discuss the cause and treatment of acute limb ischemia in
      endovascular therapy of the lower extremity arterial occlusive disease. METHODS:
      Clinical data of 54 cases of acute limb ischemia in the endovascular treatment of
      685 cases of lower extremity arterial occlusive disease from June 2003 to April
      2012 was analyzed retrospectively. There were 43 male and 11 female patients,
      with a mean age of 72.3 years (ranging from 56 to 82 years). The major causes
      which resulted in acute limb ischemia included: arterial embolization of 43
      cases, arterial thrombosis of 8 cases, arterial dissection of 3 cases. The acute
      limb ischemia occurred in the process of balloon angioplasty/stent in 36 cases,
      catheter-directed thrombolysis in 17 cases, Silverhawk atherectomy in 1 cases.
      Thirty-two cases were treated by endovascular treatment, 9 cases by surgical
      procedures (bypass or embolectomy), 13 cases by the combination of endovascular
      therapy and surgical procedures. RESULTS: Treatment were successfully
      accomplished in 50 of 54 cases, and failed in 4 cases which had surgical
      amputation. There were no deaths in all the patients. Forty-five of 54 cases were
      followed up for the average of 40.3 months. Six cases had ischemic symptoms
      recurrence in 43 artery embolization patients, in whom 4 cases were cured by
      endovascular treatment, 2 cases were cured by toe amputation. One case of bypass
      anastomotic stenosis and one case of stent restenosis were successfully cured by
      endovascular treatment in 8 arterial thrombosis patients. One cases of below-knee
      artery stent occlusion in 3 arterial dissection patients was cured by medical
      treatment. Four cases of amputation patients were followed up in good condition.
      CONCLUSIONS: Most patients of acute limb ischemia complicated in endovascular
      therapy could be treated by endovascular therapy. Surgical procedures in time is
      still the best choice for the patients in whom the endovascular therapy was not
      satisfied.

PMID- 23859328
TI  - [Comparison of single and double bundle isolate posterior cruciate ligament
      reconstruction with hamstring autograft].
AB  - OBJECTIVE: To determine if double bundle hamstring autograft posterior cruciate
      ligament (PCL) reconstruction could bring better outcomes than single bundle.
      METHODS: From June 2007 to June 2009, there were 22 subjects, including 16 male
      and 6 female patients with an average (37 +/- 13) years old (16-54 years old)
      were reconstructed with single bundle PCL reconstruction (single bundle group),
      24 subjects, including 18 male and 6 female patients with an average (37 +/- 10)
      years old (17 - 52 years old) were reconstructed with double bundle PCL
      reconstruction (double bundle group). There were no differences between the two
      groups on patients' demographics and the duration from the injury to the
      operation (P > 0.05). Clinical outcomes, KT2000 and tunnel placements of all the
      patients were measured and analyzed. RESULTS: The two groups were retrospectively
      studied and compared with a (29 +/- 9) months (24 - 55 months) follow-up.
      Operation duration of double bundle group was (92 +/- 8) minutes which was
      significantly longer than the single bundle group (78 +/- 13) minutes (t = 2.474,
      P < 0.05). IKDC, Lysholm and Tegner scores were all significantly improved at the
      last follow-up of both groups (single bundle group: t = 9.578, 13.115 and 8.165,
      P < 0.01; double bundle group: t = 4.390, 5.522 and 4.313, P < 0.05). Post
      operative KT2000 side-to-side difference of the double bundle group was
      significantly smaller than that of the single bundle group under maximum
      posterior force with the knee in 90 degrees  flexion ((1.5 +/- 1.5) mm vs. (4.0
      +/- 2.9) mm, t = 2.538, P = 0.019). There were 66.7% of the patients of double
      bundle group were normal which was significantly higher than 31.8% of the single
      bundle group on the IKDC knee examination form (chi2 = 5.576, P = 0.018).
      CONCLUSIONS: Single or double bundle PCL reconstruction could restore the knee's
      stability and function satisfied. There are no differences between two groups in
      clinical scores, but double group manifestes a better anterior-posterior
      stability.

PMID- 23859329
TI  - [Minimally invasive aortic valve replacement for isolated aortic valve disease:
      clinical analysis of 101 consecutive patients].
AB  - OBJECTIVE: To review the results for minimally invasive aortic valve replacement
      (AVR) through a 5 cm right anterolateral thoracotomy. METHODS: From July 2009 to
      September 2011, 101 consecutive patients with isolated aortic valve disease
      (degenerative in 37 patients, rheumatic in 21 patients, congenital in 37
      patients, endocarditic in 3 patients and aorta-arteritis in 1 patients) underwent
      AVR through the right anterolateral thoracotomy approach in the third intercostal
      space with a groin incision for femoral connection of cardiopulmonary bypass. The
      mean age was 45.7 years (ranging from 17 to 71 years). Sixty patients were male.
      RESULTS: Operations were successfully performed in all but 1 patient (1.0%) who
      required intraoperative conversion to full sternotomy. Mean duration of
      cardiopulmonary bypass time and aortic cross-clamp time was (88 +/- 24) minutes
      and (55 +/- 18) minutes, respectively. Thirty-day mortality was 1.0% (1/101),
      this patient was found difficult in weaning off cardiopulmonary bypass and
      exhibited severe coronary artery plaque, although bypass graft was carried out
      immediately, the patient died of severe low cardiac output syndrome finally. No
      blood products were needed in 83.2% patients. Follow-up was performed in all
      patients at an average of (16 +/- 7) months postoperatively. A good recovery was
      obtained in all patients except one who died of multiple organ failure caused by
      massive cerebral infarction 38 days after surgery. CONCLUSIONS: Minimally
      invasive aortic valve replacement though the right anterolateral thoracotomy
      approach is safe and feasible, with good cosmetic results and rapid postoperative
      recovery. It is worthy of clinical elective application.

PMID- 23859330
TI  - [Efficacy analysis of three therapeutic modes on clinical stage Ia
      nonseminomatous germ cell testicular tumors].
AB  - OBJECTIVES: To investigate the oncologic outcomes of surveillance,
      retroperitoneal lymph node dissection (RPLND) and primary chemotherapy in
      patients with clinical stage Ia nonseminomatous germ cell testicular tumors (CS
      Ia NSGCT) and to analyze risk factors for relapse. METHODS: Patients with CS Ia
      NSGCT were retrospectively reviewed. Totally 72 patients were enrolled and
      grouped according to three different treatment after orchiectomy, among them 33
      cases in surveillance group, 24 cases in RPLND group and 15 cases in primary
      chemotherapy group. Disease progressive free survival and disease specific
      survival were compared using Kaplan-Meier analysis. Cox regression analysis was
      used to confirm variables those were associated with disease progression.
      RESULTS: All 72 patients were followed-up at mean 62 months (12 - 175 months), 6
      patients had evidence of relapse. Both the 5-year disease specific survival and 5
      year overall survival rate were 100%. For surveillance, chemotherapy and RPLND,
      cumulative 5-year PFS rates were 84.0%, 93.3% and 100%, respectively. Relapse
      rate was higher in surveillance group than in RPLND group (17.8% vs. 0, chi2 =
      3.99, P = 0.04). Patients with the history of cryptorchidism also have higher
      relapse rate than without (37.5% vs. 4.7%, chi2 = 10.02, P = 0.01). In the
      surveillance cohort, relapse rates were significantly higher in patients with a
      predominant component of embryonal carcinoma (3/6 vs. 7.4%, chi2 = 6.93, P =
      0.04) and for those over 13 years of age (23.1% vs. 5.3%, chi2 = 4.33, P = 0.04).
      On multivariate analysis, treatment mode of patients (OR = 0.08, 95% CI: 0.06
      0.36, P = 0.03) and patients with a history of cryptorchidism (OR = 25.3, 95% CI:
      6.57-78.42, P = 0.04) were independent predictors of relapse. CONCLUSIONS:
      Surveillance, RPLND and adjuvant chemotherapy could be reliable strategies in
      compliant stage Ia nonseminoma patients and achieve satisfactory overall
      survival. Relapse rate is relatively higher for patients with surveillance. Those
      who are older or have a history of cryptorchidism experience a higher risk of
      relapse.

PMID- 23859331
TI  - [Molecular mechanism of gamma-aminobutyric acid inhibitory on the growth of
      cholangiocarcinoma QBC939 cell line].
AB  - OBJECTIVE: To explore the molecular mechanism of gamma-aminobutyric acid (GABA)
      inhibitory on the growth of cholangiocarcinoma cell line (QBC939). METHODS:
      QBC939 cells were cultured in different groups and treated with GABA, GABA +
      bicuculine (A receptor antagonist), GABA + phaclofen (B receptor antagonist) for
      48 hours. MTT assay was used to determine the proliferation of QBC939 cells.
      Annexin V-FITC/PI binding assay was used to detect apoptosis in the QBC939 cells.
      Western blot was applied to check the expression of signal transducer and
      activator of transcription 3 (STAT3) and phosphorylation-STAT3 (p-STAT3) proteins
      in different groups of QBC939 cells. Animal models of cholangiocarcinoma bearing
      nude mice were established by subcutaneous injection of QBC939 cells and
      randomized into 2 groups: control and GABA-treated groups. The effect of GABA was
      evaluated after 5 weeks, including the body weight and tumor volume. The
      expression of p-STAT3 was detected by immunohistochemistry and Western blot in
      xenograft tumors. RESULTS: MTT and FCM assays both showed that the effect of GABA
      inhibitory on the proliferation (15.30% +/- 0.80% vs. 2.66% +/- 0.74%, t = 23.15,
      P = 0.00) and induced apoptosis (23.15% +/- 0.21% vs. 4.30% +/- 0.69%, t = 52.40,
      P = 0.00) of QBC939 cells could be antagonized by phaclofen, but not bicuculine.
      The expression of STAT3 and p-STAT3 proteins were all observed in the QBC939
      cells and GABA significantly down-regulated p-STAT3 protein expression (0.77 +/-
      0.00 vs. 0.45 +/- 0.01, t = 63.14, P = 0.00), this action was also antagonized by
      phaclofen (0.45 +/- 0.01 vs. 0.76 +/- 0.01, t = 56.25, P = 0.00). Xenograft tumor
      volume ((0.62 +/- 0.03) cm3 vs. (0.34 +/- 0.03) cm3, t = 13.45, P = 0.00) and the
      expression of p-STAT3 protein were significantly decreased in GABA-treated group
      as compared with control group. CONCLUSIONS: GABA may inhibit the growth of
      cholangiocarcinoma cells QBC939 through GABA(B) receptor, and down-regulation of
      the p-STAT3 expression perhaps is one of its anti-tumor mechanisms.

PMID- 23859332
TI  - [The study of the protective effect and its mechanism of Edaravone to neurons
      with hydrogen peroxide stimulated].
AB  - OBJECTIVES: To prove the protective effect of Edaravone to neurons and to study
      the particular mechanism. METHODS: Neurons were collected from 18-day fetal rat
      brains and a culture of almost pure neurons was obtained after 14-day culture,
      then the cells were randomly assigned to one of the three groups: control group,
      hydrogen peroxide (H2O2)-treated group, and Edaravone-treated group. In H2O2
      treated group, 300 umol/L H2O2 was added to the medium, followed by returning to
      the normal culture for the presupposition of time. In Edaravone-treated group,
      500 umol/L Edaravone was prophylactically added to the medium for 30 minutes
      before the insult. Morphology of mitochondria was visualized by transmission
      electron microscopy. The rate of apoptotic cells was detected by flow cytometry
      analysis. The relationships between the proteins and the key proteins expressions
      were observed by immunoprecipitation and immunoblotting. RESULTS: Compared to the
      Edaravone-treated group, mitochondria in H2O2-treated group displayed more
      vesicular matrix compartments at the same time. Percentage of apoptotic cells in
      H2O2-treated group after 0.5, 2, 6 and 12 h were 14.40% +/- 1.23%, 45.50% +/-
      2.81%, 56.40% +/- 3.53%, 62.50% +/- 4.23%, which were higher than control group
      (F = 274.8, P < 0.01). Edaravone-treated group were 0.90% +/- 0.07%, 1.10% +/-
      0.08%, 3.50% +/- 1.90%, 12.60% +/- 1.10%, which were lower than H2O2-treated
      group (F = 362.7, P < 0.01). After H2O2 stimulation for 0.5 h in H2O2-treated
      group, the levels of p-JNK (Thr183/Tyr185) and cytochrome c in cytosol and BAX in
      heavy membrane were increased significantly at 0.5 h, reaching a peak at 12 h
      after stimulation, In addition, the expressions of p-BAD, BAX, BAD and 14-3-3 of
      cytoplasm decreased, however, these changes were inhibited in the Edaravone
      treated group. CONCLUSIONS: As a free radical scavenger, the Edaravone could
      protect neurons by inhibiting the activity of JNK, the disassociation of BAD from
      14-3-3 and the translocation of BAX from the cytosol to mitochondria.

PMID- 23859333
TI  - Nano-storage wires.
AB  - We report the development of "nano-storage wires" (NSWs), which can store
      chemical species and release them at a desired moment via external electrical
      stimuli. Here, using the electrodeposition process through an anodized aluminum
      oxide template, we fabricated multisegmented nanowires composed of a polypyrrole
      segment containing adenosine triphosphate (ATP) molecules, a ferromagnetic nickel
      segment, and a conductive gold segment. Upon the application of a negative bias
      voltage, the NSWs released ATP molecules for the control of motor protein
      activities. Furthermore, NSWs can be printed onto various substrates including
      flexible or three-dimensional structured substrates by direct writing or magnetic
      manipulation strategies to build versatile chemical storage devices. Since our
      strategy provides a means to store and release chemical species in a controlled
      manner, it should open up various applications such as drug delivery systems and
      biochips for the controlled release of chemicals. 

PMID- 23859334
TI  - Serum PSA as a predictor of testosterone deficiency.
AB  - INTRODUCTION: The relationship between serum prostate-specific antigen (PSA) and
      testosterone (T) levels is still controversial. According to the "saturation
      hypothesis," a significant relationship is apparent only in the low T range. AIM:
      To verify whether, in a large sample of male subjects seeking medical care for
      sexual dysfunction (SD), PSA might represent a reliable marker of T levels.
      METHODS: A consecutive series of 3,156 patients attending our unit for SD was
      studied. Among them, only subjects without history of prostate disease and with
      PSA levels<4 ng/mL (N=2,967) were analyzed. MAIN OUTCOME MEASURES: Several
      hormonal and biochemical parameters were studied, along with structured interview
      on erectile dysfunction (SIEDY), ANDROTEST, and PsychoANDROTEST. RESULTS:
      Receiver operating characteristic curve analysis for predicting severe
      hypogonadism (T<8 nmol/L) showed an accuracy of PSA=0.612+/-0.022 (P<0.0001),
      with the best sensitivity and specificity at PSA<0.65 ng/mL (65.2% and 55.5%,
      respectively). In the entire cohort, 254 subjects (8.6%) showed T<8 nmol/L and,
      among them, more than half (N=141, 4.8%) had PSA<0.65 ng/mL. After adjusting for
      age, low PSA was associated with hypogonadism-related features (i.e., delayed
      puberty, lower testis volume) and associated conditions, such as metabolic
      syndrome (hazard ratio [HR]=1.506 [1.241-1.827]; P<0.0001), type 2 diabetes
      (HR=2.044 [1.675-2.494]; P<0.0001), and cardiovascular diseases (HR=1.275 [1.006
      1.617]; P=0.045). Furthermore, low PSA was associated with impaired sex- and
      sleep-related erections. The association between low PSA and hypogonadal symptoms
      and signs as well as with metabolic syndrome was retained even after adjusting
      for T levels. Sensitivity and positive predictive values of low PSA increased,
      whereas specificity and negative predictive value decreased as a function of age.
      CONCLUSIONS: PSA is a marker of T concentrations and it may represent a new tool
      in confirming hypogonadism. The determination of PSA levels might give insights
      not only on the circulating levels of total T but also on its active fractions.

PMID- 23859335
TI  - Assessment of circulating N-terminal pro B-type natriuretic peptide concentration
      to differentiate between cardiac from noncardiac causes of pleural effusion in
      cats.
AB  - OBJECTIVE: To determine the diagnostic ability of blood N-terminal pro B-type
      natriuretic peptide (NT-proBNP) measurement to differentiate between congestive
      heart failure (CHF) and noncardiogenic causes for moderate to severe pleural
      effusion in cats. DESIGN: Prospective observational study. SETTING: University
      teaching hospital. ANIMALS: Twenty-one cats with moderate to severe pleural
      effusion. INTERVENTIONS: Venous blood sampling for NT-proBNP measurement.
      MEASUREMENT AND RESULTS: According to the results of echocardiographic
      examination, cats were classified in a group with CHF (n = 11) or noncongestive
      heart failure (N-CHF, n = 10). NT-proBNP was measured via a feline-specific test
      in EDTA plasma with protease inhibitor. NT-proBNP was significantly (P < 0.0001)
      higher in the CHF group ( median 982 pmol/L, 355-1,286 pmol/L) than in the N-CHF
      group (median 69 pmol/L, 26 - 160 pmol/L) and discriminated exactly (area under
      the curve = 1.0, 95% confidence interval 1.0-1.0) between both groups. Optimum
      cut-off value considering all samples was 258 pmol/L. CONCLUSION: In this small
      population of cats with pleural effusion, NT-proBNP was able to differentiate
      between cats with cardiogenic and noncardiogenic causes of effusion. With the
      currently recommended method of measurement (ie, EDTA plasma with protease
      inhibitor), a cut-off value of 258 pmol/L discriminates effectively between cats
      with and without CHF.

PMID- 23859336
TI  - Effect of dietary caloric restriction on the nociceptive threshold of rats that
      underwent aerobic and resistance exercise training.
AB  - The purpose of this study was to evaluate the effect that exercise and caloric
      restriction have on the nociceptive threshold of rats. Male Wistar rats were
      divided into two groups: one group that was fed ad libitum (FED) and another
      group that was subjected to dietary caloric restriction (CR). The CR group
      received 50% of the food the FED group received, for 4 weeks. Both groups were
      submitted to aerobic (AE) and resistance (RE) exercise training protocols
      performed in a rodent treadmill and in a weight-lifting exercise model,
      respectively. Mechanical and thermal nociceptive thresholds were measured by tail
      flick and paw-withdrawal tests, respectively. Both exercise protocols produced
      antinociception, but there was no difference found between the FED and CR groups
      after either 1 or 4 weeks. Additionally, although dietary caloric restriction
      alone did not result in antinociception, it did increase the running time of
      animals during aerobic exercise and increased the load lifted in resistance
      exercise after 4 weeks. These results indicate that caloric restriction for 1 or
      4 weeks did not alter the nociceptive threshold, but could play an important role
      in improvement of physical performance. 

PMID- 23859337
TI  - Nikolaus Friedreich and degenerative atrophy of the dorsal columns of the spinal
      cord.
AB  - Nikolaus Friedreich (1825-1882) presented clinical findings in six patients with
      a severe hereditary disorder of the nervous system and secured full autopsies in
      four of them. He was fascinated by the spinal cord lesions in the siblings of two
      unrelated families, and in the first three of his five long articles stressed the
      destruction of the dorsal columns. He recognized the relatively minor symmetrical
      lesions of the anterolateral fasciculi but did not separate dorsal
      spinocerebellar tracts (Flechsig's bundles) and corticospinal tracts. Although he
      studied the dorsal spinal roots in great detail and established their principal
      abnormality, namely, axonal thinning without axonal loss, he reported dorsal root
      ganglia as entirely normal. He made an insightful description of atrophic neurons
      in the gracile nuclei (clavae) but overlooked the invariable atrophy of the
      dentate nuclei. He followed the families over a period of 14 years, but
      acknowledged the hereditary nature of the disease only very late. He proposed a
      developmental defect for the medulla oblongata, retaining his interpretation that
      the spinal lesion was inflammatory. This review honors Friedreich for his insight
      into a 'new' disease in the late 19th century and updates his neuropathological
      findings. It is remarkable that Friedreich also described the abnormal hearts in
      the disease that now bears his name since hypertrophic cardiomyopathy is now
      recognized as the main cause of death in Friedreich's ataxia.

PMID- 23859338
TI  - Prevalence gradients of Friedreich's ataxia and R1b haplotype in Europe co
      localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice
      age refuge.
AB  - Combining data from epidemiological studies in Friedreich's Ataxia (FRDA) and
      patient organization membership lists, shows that FRDA prevalence exhibits large
      regional differences in Europe with a prevalence gradient from west to east.
      Highest levels are observed in northern Spain, south of France and Ireland,
      lowest levels in Scandinavia and Russia. The observed distribution of FRDA in
      Europe co-localizes with the gradient of the chromosomal R1b marker as detected
      within west Europe. This gradient is either derived from Palaeolithic migrations
      out of the Franco-Cantabrian Ice age refuge or from Neolithic migrations entering
      west Europe with the advance of agriculture. FRDA prevalence may have been
      increased in this population anytime after its separation from the closely
      related R1a carrying group. East European populations with a high frequency of
      the R1a marker show 10 fold lower prevalence of FRDA, indicating that the FRDA
      mutation was present in the common ancestor and was increased in the R1b carrying
      group. The FRDA carrying population went through a Palaeolithic population
      bottleneck supporting the view that the observed FRDA distribution and
      potentially the R1b distribution are derived from Palaeolithic migrations out of
      the Franco-Cantabrian ice age refuge. 

PMID- 23859339
TI  - Gene regulation and epigenetics in Friedreich's ataxia.
AB  - This is an exciting time in the study of Friedreich's ataxia. Over the last 10
      years much progress has been made in uncovering the mechanisms, whereby the
      Frataxin gene is silenced by (GAA)n repeat expansions and several of the findings
      are now ripe for testing in the clinic. The discovery that the Frataxin gene is
      heterochromatinised and that this can be antagonised in vivo has led to the
      tantalizing possibility that the disease might be amenable to a more radical
      therapeutic approach involving epigenetic modifiers. Here, we set out to review
      progress in the understanding of the fundamental mechanisms whereby genes are
      regulated at this level and how these findings have been applied to achieve a
      deeper understanding of the dysregulation that occurs as the primary genetic
      lesion in Friedreich's ataxia.

PMID- 23859340
TI  - Frataxin: a protein in search for a function.
AB  - Reduced levels of the protein frataxin cause the neurodegenerative disease
      Friedreich's ataxia. Pathology is associated with disruption of iron-sulfur
      cluster biosynthesis, mitochondrial iron overload, and oxidative stress. Frataxin
      is a highly conserved iron-binding protein present in most organisms. Despite the
      intense interest generated since the determination of its pathology,
      identification of the cellular function of frataxin has so far remained elusive.
      In this review, we revisit the most significant milestones that have led us to
      our current understanding of frataxin and its functions. The picture that emerges
      is that frataxin is a crucial element of one of the most essential cellular
      machines specialized in iron-sulfur cluster biogenesis. Future developments,
      therefore, can be expected from further advancements in our comprehension of this
      machine. 

PMID- 23859341
TI  - Mitochondrial pathophysiology in Friedreich's ataxia.
AB  - Neurological examination indicates that Friedreich's ataxia corresponds to a
      mixed sensory and cerebellar ataxia, which affects the proprioceptive pathways.
      Neuropathology and pathophysiology of Friedreich's ataxia involves the peripheral
      sensory nerves, dorsal root ganglia, posterior columns, the spinocerebellar, and
      corticospinal tracts of the spinal cord, gracile and cuneate nuclei, dorsal
      nuclei of Clarke, and the dentate nucleus. Involvement of the myocardium and
      pancreatic islets of Langerhans indicates that it is also a systemic disease. The
      pathophysiology of the disease is the consequence of frataxin deficiency in the
      mitochondria and cells. Some of the biological consequences are currently
      recognized such as the effects on iron-sulfur cluster biogenesis or the oxidative
      status, but others deserve to be studied in depth. Among physiological aspects of
      mitochondria that have been associated with neurodegeneration and may be
      interesting to investigate in Friedreich's ataxia we can include mitochondrial
      dynamics and movement, communication with other organelles especially the
      endoplasmic reticulum, calcium homeostasis, apoptosis, and mitochondrial
      biogenesis and quality control. Changes in the mitochondrial physiology and
      transport in peripheral and central axons and mitochondrial metabolic functions
      such as bioenergetics and energy delivery in the synapses are also relevant
      functions to be considered. Thus, to understand the general pathophysiology of
      the disease and fundamental pathogenic mechanisms such as dying-back axonopathy,
      and determine molecular, cellular and tissue therapeutic targets, we need to
      discover the effect of frataxin depletion on mitochondrial properties and on
      specific cell susceptibility in the nervous system and other affected organs. 

PMID- 23859342
TI  - Animal and cellular models of Friedreich ataxia.
AB  - The development and use of animal and cellular models of Friedreich ataxia (FRDA)
      are essential requirements for the understanding of FRDA disease mechanisms and
      the investigation of potential FRDA therapeutic strategies. Although animal and
      cellular models of lower organisms have provided valuable information on certain
      aspects of FRDA disease and therapy, it is intuitive that the most useful models
      are those of mammals and mammalian cells, which are the closest in physiological
      terms to FRDA patients. To date, there have been considerable efforts put into
      the development of several different FRDA mouse models and relevant FRDA mouse
      and human cell line systems. We summarize the principal mammalian FRDA models,
      discuss the pros and cons of each system, and describe the ways in which such
      models have been used to address two of the fundamental, as yet unanswered,
      questions regarding FRDA. Namely, what is the exact pathophysiology of FRDA and
      what is the detailed genetic and epigenetic basis of FRDA? 

PMID- 23859343
TI  - Erythropoietin in Friedreich ataxia.
AB  - In Friedreich ataxia (FRDA), several candidate substances including
      erythropoietin (EPO) focus on increase in the amount of frataxin and aim to
      counteract the consequences of frataxin deficiency. Evidence for recombinant
      human erythropoietin (rHuEPO) in FRDA is based on in vitro studies using mouse
      neuronal cell lines, human fibroblasts, cardiomyocytes, and primary lymphocytes
      from FRDA patients or control subjects which showed a dose-dependent increase of
      frataxin after incubation with different erythropoietins. The mechanism by which
      EPO induces frataxin increase remains to be elucidated, but may involve post
      transcriptional and/or post-translational modifications of frataxin or
      alterations in frataxin half-life and metabolism. In vivo data on rHuEPO's
      ability to increase frataxin in FRDA patients is contradictory as studies on the
      effect of EPO derivatives in FRDA differ in treatment regimen, sample size, and
      duration. Open-label studies indicate for sustained frataxin increase, decrease
      of oxidative stress, and clinical improvement in FRDA patients after
      administration of rHuEPO. Two randomized controlled studies found acceptable
      safety and tolerability of EPO derivatives in FRDA. Secondary outcome measures,
      however, such as frataxin up-regulation and clinical efficacy were not met. This
      review will focus on (i) pre-clinical work on erythropoietins in FRDA and (ii)
      clinical studies in FRDA patients exposed to erythropoietins. 

PMID- 23859344
TI  - Cardiomyopathy of Friedreich ataxia.
AB  - Friedreich's ataxia is a rare hereditary, predominantly neurologically defined
      multisystem disorder of mitochondrial function. Although the gene defect has been
      identified, the precise pathophysiology of the deficient mitochondrial protein,
      frataxin, is unknown. Besides the characteristic features of spinocerebellar
      ataxia the heart may also be affected, and patients may experience a hypertrophic
      cardiomyopathy eventually progressing toward heart failure and death. So far,
      research focused on the neurological aspects and little attention has been paid
      to better characterize and understand the cardiac involvement in Friedreich's
      ataxia. For that, a better understanding of longitudinal progression, cardiac
      complications and long-term cardiac outcome is warranted. In addition, the
      clinician should be familiar with the therapeutic option in Friedreich
      cardiomyopathy. This review discusses important clinical and diagnostic features
      of the cardiomyopathy in Friedreich's ataxia and potential therapeutic
      developments. 

PMID- 23859345
TI  - Diabetes in Friedreich ataxia.
AB  - Diabetes is a common metabolic disorder in patients with Friedreich ataxia. In
      this Supplement article, we review the clinical data on diabetes in Friedreich
      ataxia, and the experimental data from rodent and in vitro models of the disease.
      Increased body adiposity and insulin resistance are frequently present in
      Friedreich ataxia, but pancreatic beta cell dysfunction and death are a conditio
      sine qua non for the loss of glucose tolerance and development of diabetes. The
      loss of frataxin function in mitochondria accounts for these pathogenic processes
      in Friedreich ataxia. Mitochondria are essential for the sensing of nutrients by
      the beta cell and for the generation of signals that trigger and amplify insulin
      secretion, known as stimulus-secretion coupling. Moreover, in the intrinsic
      pathway of apoptosis, pro-apoptotic signals converge on mitochondria, resulting
      in mitochondrial Bax translocation, membrane permeabilization, cytochrome c
      release and caspase cleavage. How and at which level frataxin deficiency impacts
      on these processes in beta cells is only partially understood. A better
      understanding of the molecular mechanisms mediating beta cell demise in
      Friedreich ataxia will pave the way for new therapeutic approaches. 

PMID- 23859346
TI  - Clinical features of Friedreich's ataxia: classical and atypical phenotypes.
AB  - One hundred and fifty years since Nikolaus Friedreich's first description of the
      degenerative ataxic syndrome which bears his name, his description remains at the
      core of the classical clinical phenotype of gait and limb ataxia, poor balance
      and coordination, leg weakness, sensory loss, areflexia, impaired walking,
      dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities,
      cardiomyopathy and diabetes. Onset is typically around puberty with slow
      progression and shortened life-span often related to cardiac complications.
      Inheritance is autosomal recessive with the vast majority of cases showing an
      unstable intronic GAA expansion in both alleles of the frataxin gene on
      chromosome 9q13. A small number of cases are caused by a compound heterozygous
      expansion with a point mutation or deletion. Understanding of the underlying
      molecular biology has enabled identification of atypical phenotypes with late
      onset, or atypical features such as retained reflexes. Late-onset cases tend to
      have slower progression and are associated with smaller GAA expansions. Early
      onset cases tend to have more rapid progression and a higher frequency of non
      neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus.
      Compound heterozygotes, including those with large deletions, often have atypical
      features. In this paper, we review the classical and atypical clinical phenotypes
      of Friedreich's ataxia. 

PMID- 23859347
TI  - Monitoring progression in Friedreich ataxia (FRDA): the use of clinical scales.
AB  - Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder associated
      with ataxia, dysarthria, pyramidal tract signs, sensory loss, cardiomyopathy and
      diabetes. There is no cure for FRDA so far. Studies of the natural history of the
      disease and future therapeutic trials require development of appropriate outcome
      markers. Since any therapeutic benefit is expected to modulate deterioration over
      time rather than to reverse disability, potential outcome measures must be
      sensitive instruments carefully analysed for their significance. Clinical scales
      may represent an appropriate measuring tool. Over the last few years the
      construction, evaluation and validation of sensitive clinical scales for the
      assessment of disease severity and progression in ataxia have had considerable
      impact on our understanding of the disease. Currently, there are three different
      scales that are most frequently applied: The International Cooperative Ataxia
      Rating Scale (ICARS), the Friedreich Ataxia Rating Scale (FARS) and the Scale for
      the Assessment and Rating of Ataxia (SARA). All scales have been validated and
      compared with regard to their testing properties. 

PMID- 23859348
TI  - Co-enzyme Q10 and idebenone use in Friedreich's ataxia.
AB  - Friedreich's ataxia is a debilitating progressive neurodegenerative disease
      associated with cardiomyopathy and other features. The underlying cause is a
      deficiency of the mitochondrial protein frataxin which causes mitochondrial iron
      deposition, increased oxidative stress and impaired adenosine triphosphate
      production. Over the last 15 years, multiple clinical trials have assessed the
      efficacy of antioxidant agents in this disease. This article reviews trials of
      the two most important agents, namely co-enzyme Q10 and idebenone.

PMID- 23859349
TI  - Deferiprone for the treatment of Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA) is a neurological disease related to a deficiency of
      the protein frataxin involved in iron-sulfur (Fe-S) cluster biogenesis. This
      leads to an increased cellular iron uptake accumulating in mitochondria, and a
      subsequently disturbed iron homeostasis. The detailed mechanism of iron
      regulation of frataxin expression is yet unknown. Deferiprone, an iron chelator
      that may cross the blood-brain barrier, was shown to shuttle iron between
      subcellular compartments. It could also transfer iron from iron-overloaded cells
      to extracellular apotransferrin and pre-erythroid cells for heme synthesis. Here,
      clinical studies on Deferiprone are reviewed in the context of alternative agents
      such as desferoxamine, with specific regard to its mechanistic and clinical
      implications. 

PMID- 23859351
TI  - Effective Hamiltonian Crystal Field as applied to magnetic exchange parameters in
      MU-oxo-bridged Cr(III) dimers.
AB  - The calculation of the 3d-intrashell excitations in coordination compounds by
      means of the Effective Hamiltonian Crystal Field (EHCF) method is generalized to
      their polynuclear analogues to properly describe several open d-shells and their
      magnetic interactions. This challenge requires improving the precision of ca.
      1000 cm(-1) to ca. 100 cm(-1) characteristic for the spin-reorientation energies.
      The method follows the successful EHCF paradigm, namely, the concerted usage of
      McWeeny's group-function approximation and Lowdin's partitioning technique, for
      an effective description of the multicenter d-systems. The novel approach is
      implemented in the MagAixTic package and validated against a series of binuclear
      complexes of Cr(III) featuring MU-oxygen superexchange paths. The trends in the
      compound series in terms of exchange constants are correctly reproduced, despite
      differing details of composition and structure, and the numerical results agree
      by order of magnitude with available experimental data and other theoretical
      methods.

PMID- 23859350
TI  - Increasing frataxin gene expression with histone deacetylase inhibitors as a
      therapeutic approach for Friedreich's ataxia.
AB  - The genetic defect in Friedreich's ataxia (FRDA) is the expansion of a GAA.TCC
      triplet in the first intron of the FXN gene, which encodes the mitochondrial
      protein frataxin. Previous studies have established that the repeats reduce
      transcription of this essential gene, with a concomitant decrease in frataxin
      protein in affected individuals. As the repeats do not alter the FXN protein
      coding sequence, one therapeutic approach would be to increase transcription of
      pathogenic FXN genes. Histone posttranslational modifications near the expanded
      repeats are consistent with heterochromatin formation and FXN gene silencing. In
      an effort to find small molecules that would reactivate this silent gene, histone
      deacetylase inhibitors were screened for their ability to up-regulate FXN gene
      expression in patient cells and members of the pimelic 2-aminobenzamide family of
      class I histone deacetylase inhibitors were identified as potent inducers of FXN
      gene expression and frataxin protein. Importantly, these molecules up-regulate
      FXN expression in human neuronal cells derived from patient-induced pluripotent
      stem cells and in two mouse models for the disease. Preclinical studies of safety
      and toxicity have been completed for one such compound and a phase I clinical
      trial in FRDA patients has been initiated. Furthermore, medicinal chemistry
      efforts have identified improved compounds with superior pharmacological
      properties. 

PMID- 23859352
TI  - Effects of a Fusarium toxin-contaminated maize treated with sodium
      metabisulphite, methylamine and calcium hydroxide in diets for female piglets.
AB  - Deoxynivalenol (DON) and zearalenone (ZEN) contaminated maize was hydrothermally
      treated in the presence of sodium metabisulphite (SBS), methylamine and calcium
      hydroxide (Ca(OH)2) and included into diets for female piglets to evaluate
      effects on performance, organ weights, development of hyperestrogenism, serum
      biochemical parameters, stimulation of peripheral blood mononuclear cells and
      toxin residues in serum. For this purpose, both uncontaminated maize (CON) and
      Fusarium toxin-contaminated maize (FUS) were included into diets either untreated
      (-) or treated (+) according to a 2 by 2-factorial design. One-hundred female
      weaned piglets were assigned to one of the four treatment groups (n = 25) CON-,
      CON+, FUS- and FUS+ with DON/ZEN concentrations of 0.43/0.03, 0.04/0.0, 3.67/0.32
      and 0.36/0.08 mg per kg diet, respectively. After a feeding period of 27 days, 20
      piglets (n = 5) were slaughtered. Performance parameters such as feed intake,
      live weight gain and feed-to-gain ratio remained unaffected by the treatments.
      Uterus weights were significantly reduced in group FUS+ compared to FUS- (p =
      0.028), while visceral organ weights were not influenced. Vulva width in relation
      to body weight was highest in group FUS- at the end of the trial, while
      hydrothermal treatment significantly reduced the parameter (p < 0.01). The
      highest toxin and toxin metabolite concentrations in serum were detected in group
      FUS-, whereas ingestion of diet FUS+ reduced the concentrations to the level of
      the control groups. Serum biochemical and haematological parameters were mainly
      within the given reference ranges and showed no treatment-related alterations.
      Stimulation of peripheral blood mononuclear cells was not affected. An effective
      detoxification of maize by hydrothermal treatment in the presence of SBS,
      methylamine and Ca(OH)2 could be demonstrated by means of serum toxin analyses.
      No undesired side effects of the treated-feed stuff or the chemicals themselves
      on the health of piglets were detected. 

PMID- 23859353
TI  - Exploring lubrication regimes at the nanoscale: nanotribological characterization
      of silica and polymer brushes in viscous solvents.
AB  - Nanotribological properties of silica surfaces, with and without adsorbed,
      brushlike copolymers of poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG)
      and poly(L-lysine)-graft-dextran (PLL-g-dextran) have been investigated in
      aqueous viscous solvent mixtures by means of colloid-probe lateral force
      microscopy. Lateral forces for PEG/dextran brushes have been measured as a
      function of shear velocity in aqueous mixtures of glycerol and ethylene glycol
      (EG), which are highly miscible with water, but are poor solvents for hydrophilic
      PEG and dextran chains. Prior to the friction measurements on polymer brushes, a
      nanoscale Stribeck curve was obtained on a bare silica surface in the selected
      aqueous cosolvent mixtures. The Stribeck curve for bare surfaces indicates the
      existence of a surface-solvating thin film due to the adsorption of hydrated
      ions, preventing direct silica-silica contact in the boundary-lubrication regime.
      A clear transition to the hydrodynamic regime is seen at high speeds for solvents
      with higher viscosities. The polymer brushes, however, show a shear-thinning
      effect with increasing shear speed and a combined influence of polymer film and
      solvent viscosity on the measured friction forces. The formation of an
      interfacial fluid-film is shown to shift the hydrodynamic regime of hydrated
      brushes to a lower value of Ueta. The correlation between the structural
      configuration and the corresponding frictional properties of the polymer brushes
      upon changing solvent quality is discussed.

PMID- 23859355
TI  - Physiochemical characterization of beta-glucan and in vitro release of
      lactoferrin from beta-glucan microparticles.
AB  - The average molecular mass of beta-glucan was 241,700 g/mol with a polydispersity
      of 1.433. At lower concentrations, gels showed Newtonian flow behaviour and shear
      thinning properties at higher concentrations. There was no effect of pH on the
      flow properties of the beta-glucans at lower concentrations of 1% while at higher
      concentrations of 4% and above viscosity increased with pH 4 or greater. A
      progressive decrease in viscosity with increasing temperature for all
      concentrations of samples tested at a constant shear rate was observed. A set gel
      structure was not formed below 3% beta-glucan so 2% solutions were used to
      incorporate lactoferrin at room temperature prior to film casting and cryomilling
      to prepare microparticles. There was an initial burst lactoferrin release from
      all microparticles, with final amount released after 7 hours only 35 and 32 % for
      beta-glucan alone or with the addition of PEG 2000 respectively. Final
      lactoferrin release after 7 hours was 91% when Kolicoat was added to the
      formulation. Stress studies on beta-glucan indicated that there was no
      degradation of the beta-glucan at gastric conditions of low pH, which suggests
      that beta-glucan might protect fragile molecules under gastric conditions. 

PMID- 23859356
TI  - Solid dispersion in pharmaceutical drug development: from basics to clinical
      applications.
AB  - The solubility of drugs is one of the most challenging aspects in developing
      formulations for novel drug discovery. Myriad of approaches have been developed
      and tested to overcome the associated intricacies involved with poor water
      soluble drugs. Out of the available technologies, solid dispersion (SD) method
      that significantly enhances the solubility and bioavailability by reducing
      particle size to a micro-molecular level is often viewed as a promising strategy.
      Although conceptual basis of manufacturing processes involved in SD method have
      been reported, formulation characteristics addressing solubility issues remains
      yet elusive. The current review portray the historical milestones,
      classification, probable mechanisms for enhancement of solubility, manufacturing
      processes at commercial level along with pioneer breakthroughs in field that
      enunciates the versatile pharmaceutical application for categories including anti
      cancer and anti-retroviral drugs. Besides, our article also highlights the
      translational implications of drug development by SD method hitherto unreported. 

PMID- 23859354
TI  - Computerized assessment of competence-related abilities in living liver donors:
      the Adult-to-Adult Living Donor Liver Transplantation Cohort Study.
AB  - BACKGROUND: Despite its importance, determination of competence to consent to
      organ donation varies widely based on local standards. We piloted a new tool to
      aid transplant centers in donor assessment. METHODS: We assessed competence
      related abilities among potential living liver donors (LDs) in the nine-center
      A2ALL study. Prospective LDs viewed an educational video and were queried to
      assess Understanding, Appreciation, Reasoning, and ability to express a Final
      Choice using the MacArthur Competence Assessment Tool for Clinical Research,
      adapted for computerized administration in LDs ("MacLiver"). Videotaped responses
      were scored by a clinical neuropsychologist (JF). RESULTS: Ninety-three LDs were
      assessed. Mean (standard deviation; domain maximum) scores were as follows:
      Understanding: 18.1 (2.6; max = 22), Appreciation: 5.1 (1.0; max = 6), Reasoning:
      3.1 (0.8; max = 4), and Final Choice: 3.8 (0.5; max = 4). Scores did not differ
      by demographics, relationship to the recipient, eligibility to donate, or
      eventual donation (p > 0.4). Higher education was associated with greater
      Understanding (p = 0.004) and Reasoning (p = 0.03). CONCLUSION: Standardized,
      computerized education with independent ratings of responses may (1) alert the
      clinical staff to potential donors who may not be competent to donate and (2)
      highlight areas needing further assessment and education, leading to better
      informed decision making.

PMID- 23859357
TI  - Development of controlled release osmotic pump tablet of glipizide solid
      dispersion.
AB  - PURPOSE: To develop controlled release osmotic pump tablets (COPT) of glipizide
      (GZ) solid dispersion (SD). METHODS: In elementary osmotic pump (EOP) tablets, an
      osmotic core with the drug is surrounded by a semi-permeable membrane which is
      drilled with a delivery orifice. COPT tablets eliminate the need of drilling
      process as controlled release can be achieved by the presence of osmogen in the
      coating. Poorly water soluble drug molecule cannot give satisfactory drug release
      hence GZ solid dispersion was prepared in the present study. The SDs having
      different ratio of drug to Poloxamer (PXM) 188 were prepared by hot melt method
      and optimized by solubility study, drug content estimation and in vitro
      dissolution study. Effect of two independent variables, amount of osmogen
      (potassium chloride) and hydrophilic polymer (polyethylene oxide WSR 303), were
      investigated using 3(2) factorial design. Core and coated tablets were evaluated
      for pharmacotechnical parameters. In-vitro drug release profiles of COPT tablets
      were compared with marketed with push-pull osmotic pump tablet, Glucotrol XL.
      RESULTS: Prepared core and coated tablets showed acceptable pharmacotechnical
      parameters. Drug release was directly proportional to initial level of
      hydrophilic polymer, but inversely related to the osmogen, confirming osmotic
      mechanism. Zero order drug release pattern was achieved which was comparable to
      marketed product. CONCLUSION: Novel oral controlled release of glipizide was
      successfully achieved by incorporating glipizide solid dispersion into osmotic
      system.

PMID- 23859358
TI  - Glycosylated liposomes with proton sponge capacity: novel hepatocyte- specific
      gene carriers.
AB  - Interest in hepatocyte-directed liposomal gene delivery is driven, in part, by
      the lack of effective treatment for several liver-associated disorders. To impart
      a hepatocyte targeting capability on DNA-lipoplexes, and to promote early release
      of cargo DNA from endosomes, novel glycosylated and imidazolylated cholesteryl
      derivatives have been synthesized and evaluated in vitro. Thus cholesteryl-3beta
      N-[(lactobionyl) amino] carbamate (Chol-LAC) and cholesteryl-3beta-N- [(urocanyl)
      amino] carbamate (Chol-UAC) have been formulated with the cytofectin cholesteryl
      3beta-[(N',N'- dimethylaminopropyl) carbamate (Chol-T) and the neutral co-lipid
      dioleoylphosphatidyl ethanolamine (DOPE). Liposomes, which displayed a buffering
      capability at endosomal pH, effectively bound DNA at a N/P ratio of 0.8:1 and
      offered partial protection against serum nuclease digestion. The MTT cell
      viability assay showed that lipoplexes were well tolerated by human hepatoma
      cells (HepG2), which were efficiently transfected almost exclusively by
      asialoglycoprotein receptor (ASGP-R)-mediation, as demonstrated in competition
      assays. In the ASGP-R-negative human kidney cell line (HEK293) transfection
      levels were considerably lower (P < 0.001). Therefore the combination of Chol-LAC
      and Chol- UAC in cationic liposomal formulations may provide a platform for the
      development of useful hepatotropic gene delivery systems. 

PMID- 23859359
TI  - Ultrasonic vibration-assisted pelleting of wheat straw: a predictive model for
      energy consumption using response surface methodology.
AB  - Cellulosic biomass can be used as a feedstock for biofuel manufacturing.
      Pelleting of cellulosic biomass can increase its bulk density and thus improve
      its storability and reduce the feedstock transportation costs. Ultrasonic
      vibration-assisted (UV-A) pelleting can produce biomass pellets whose density is
      comparable to that processed by traditional pelleting methods (e.g. extruding,
      briquetting, and rolling). This study applied response surface methodology to the
      development of a predictive model for the energy consumption in UV-A pelleting of
      wheat straw. Effects of pelleting pressure, ultrasonic power, sieve size, and
      pellet weight were investigated. This study also optimized the process parameters
      to minimize the energy consumption in UV-A pelleting using response surface
      methodology. Optimal conditions to minimize the energy consumption were the
      following: ultrasonic power at 20%, sieve size at 4 mm, and pellet weight at 1g,
      and the minimum energy consumption was 2.54 Wh.

PMID- 23859360
TI  - The relationship between blood lead levels and morbidities among workers employed
      in a factory manufacturing lead-acid storage battery.
AB  - The present study was carried out to find the relationship between blood lead
      levels (BLLs) and morbidities among 391 male workers employed in a factory
      manufacturing lead-acid storage batteries. A predesigned questionnaire was used
      to collect information on subjective health complaints and clinical observation
      made during a clinical examination. In addition to monitoring of BLL, other
      laboratory parameters investigated included hematological and urine-delta
      aminolevulinic acid levels. Logistic regression method was used to evaluate the
      relationship between BLL and morbidities. The BLL among workers was associated
      with an odd ratio of respiratory, gastrointestinal (GI), and musculoskeletal
      (MSD) morbidities. Mean corpuscular hemoglobin and packed cell volume variables
      were associated with respiratory problems. The variables of alcohol consumption
      and hematological parameters were associated with GI complaints. Systolic blood
      pressure was related to MSD in workers exposed to Pb during the manufacturing
      process. 

PMID- 23859361
TI  - The developmental trajectory of vocal and event-related potential responses to
      frequency-altered auditory feedback.
AB  - Speech motor control develops gradually as the acoustics of speech are mapped
      onto the positions and movements of the articulators. In this event-related
      potential (ERP) study, children and adults aged 4-30 years produced vocalizations
      while exposed to frequency-altered feedback. Vocal pitch variability and the
      latency of vocal responses were found to differ as a function of age. ERP
      responses indexed by the P1-N1-P2 complex were also modulated as a function of
      age. P1 amplitudes decreased with age, whereas N1 and P2 amplitudes increased
      with age. In addition, a correlation between vocal variability and N1 amplitudes
      was found, suggesting a complex interaction between behavioural and neurological
      responses to frequency-altered feedback. These results suggest that the neural
      systems that integrate auditory feedback during vocal motor control undergo
      robust changes with age and physiological development. 

PMID- 23859362
TI  - A study of adult pedestrian head impact conditions and injury risks in passenger
      car collisions based on real-world accident data.
AB  - OBJECTIVE: The aim of the current study was to study the kinematics of adult
      pedestrians and assess head injury risks based on real-world accidents. METHODS:
      A total of 43 passenger car versus pedestrian accidents, in which the
      pedestrian's head impacted the windscreen, were selected from accident databases
      for simulation study. According to real-world accident investigation, accident
      reconstructions were conducted using multibody system (MBS) pedestrian and car
      models under MADYMO environment (Strasbourg University) to calculate head impact
      conditions in terms of head impact velocity, head position, and head orientation.
      Pedestrian head impact conditions from MADYMO simulation results were then used
      to set the initial conditions in a simulation of a head striking a windscreen
      using finite element (FE) approach. RESULTS: The results showed strong
      correlations between vehicle impact velocity and head contact time, throw
      distance, and head impact velocity using a quadratic regression model. In the
      selected samples, the results indicated that Abbreviated Injury Scale (AIS) 2+
      and AIS 3+ severe head injuries with probability of 50 percent were caused by
      head impact velocity at about 33 and 49 km/h, respectively. Further, the
      predicted head linear acceleration (head injury criterion, HIC) value, resultant
      angular velocity, and resultant angular acceleration for 50 percent probability
      of AIS 2+ and AIS 3+ head injury risk were 116 g, 825, 40 rad/s, 11,368 rad/s(2)
      and 162 g, 1442, 55 rad/s, 18,775 rad/s(2), respectively, and the predicted value
      of 50 percent probability of skull fracture was 135 g. CONCLUSIONS: The present
      study provides new insight into pedestrian head impact conditions in terms of
      velocity, angle, and impact location based on a number of real-world cases.
      Therefore, it may perform a critical analysis for current pedestrian head
      standard tests.

PMID- 23859363
TI  - Radioresistant Sf9 insect cells undergo an atypical form of Bax-dependent
      apoptosis at very high doses of gamma-radiation.
AB  - PURPOSE: To investigate the underlying mechanisms of cell-death at extremely high
      doses of radiation in radioresistant Spodoptera frugiperda-9 (Sf9) insect cells.
      MATERIALS AND METHODS: Morphology, cell proliferation and DNA-fragmentation
      analysis was performed at 500-2000 Gy. Changes in intracellular reactive oxygen
      species (ROS), mitochondrial membrane potential (MMP), cardiolipin oxidation and
      Annexin-V externalization were studied using flow-cytometry. Cytochrome-c release
      was measured using immunofluorescence microscopy. Inhibitors of apoptosis, i.e.,
      Bongkrekic acid (BKA), Caspase-9 inhibitor (C9i), 5-(4-fluorosulfonylbenzoyl)
      adenosine hydrochloride (FSBA) and Cyclosporin-A (CsA) were used to dissect
      apoptotic mechanism at many classical steps. Caspase-3 activity was measured
      using a caspase-activity assay kit. RESULTS: A dose-dependent induction of
      typical apoptosis was observed at extremely high doses, marked by extensive
      apoptotic body formation. However, certain atypical responses such as cellular
      hypertrophy and the lack of phosphatidylserine-externalization were observed
      during the initial hours after radiation. Loss of mitochondrial membrane
      potential observed at 48 h following a 2000 Gy dose was accompanied by an
      increase in ROS that caused significant cardiolipin oxidation leading to
      cytochrome-c release, caspase activation and internucleosomal DNA fragmentation.
      Inhibitors of B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax)-mediated
      cytochrome-c release, apoptosome formation and caspase-9 effectively prevented
      radiation-induced apoptosis, strongly suggesting the role of Bax-dependent cell
      death mechanism. CONCLUSIONS: Our study demonstrates that the Sf9 insect cells
      display good homology with human cells in the mitochondria-dependent events
      during radiation-induced apoptosis, although doses eliciting similar responses
      were 50-200 times higher than human cells. Factors upstream to mitochondrial
      damage remain pertinent for a thorough understanding of this extreme
      radioresistance displayed by lepidopteran cells.

PMID- 23859364
TI  - Parallel speciation or long-distance dispersal? Lessons from seaweeds (Fucus) in
      the Baltic Sea.
AB  - Parallel evolution has been invoked as a forceful mechanism of ecotype and
      species formation in many animal taxa. However, parallelism may be difficult to
      separate from recently monophyletically diverged species that are likely to show
      complex genetic relationships as a result of considerable shared ancestral
      variation and secondary hybridization in local areas. Thus, species' degrees of
      reproductive isolation, barriers to dispersal and, in particular, limited
      capacities for long-distance dispersal will affect demographical structures
      underlying mechanisms of divergent evolution. Here, we used nine microsatellite
      DNA markers to study intra- and interspecific genetic diversity of two recently
      diverged species of brown macroalgae, Fucus radicans (L. Bergstrom & L. Kautsky)
      and F. vesiculosus (Linnaeus), in the Baltic Sea. We further performed
      biophysical modelling to identify likely connectivity patterns influencing the
      species' genetic structures. For each species, we found intraspecific contrasting
      patterns of clonality incidence and population structure. In addition, strong
      genetic differentiation between the two species within each locality supported
      the existence of two distinct evolutionary lineages (FST  = 0.15-0.41). However,
      overall genetic clustering analyses across both species' populations revealed
      that all populations from one region (Estonia) were more genetically similar to
      each other than to their own taxon from the other two regions (Sweden and
      Finland). Our data support a hypothesis of parallel speciation. Alternatively,
      Estonia may be the ancestral source of both species, but is presently isolated by
      oceanographic barriers to dispersal. Thus, a limited gene flow in combination
      with genetic drift could have shaped the seemingly parallel structure. 

PMID- 23859365
TI  - Fluorapatite enhances mineralization of mesenchymal/endothelial cocultures.
AB  - In addition to the widely used mesenchymal stem cells (MSCs), endothelial cells
      appear to be a favorable cell source for hard tissue regeneration. Previously,
      fluorapatite was shown to stimulate and enhance mineralization of MSCs. This
      study aims to investigate the growth of endothelial cells on synthesized ordered
      fluorapatite surfaces and their effect on the mineralization of adipose-derived
      stem cells (ASCs) through coculture. Endothelial cells were grown on fluorapatite
      surfaces and characterized by cell counting, flow cytometry, scanning electron
      microscopy, and enzyme-linked immunosorbent assay (ELISA). Cells were then
      cocultured with ASCs and stained for alkaline phosphatase and mineral formation.
      Fibroblast growth factor (FGF) pathway perturbation and basic FGF (bFGF)
      treatment of the ASCs were also conducted to observe their effects on
      differentiation and mineralization of these cells. Fluorapatite surfaces showed
      good biocompatibility in supporting endothelial cells. Without a mineralization
      supplement, coculture with endothelial cells induced osteogenic differentiation
      of ASCs, which was further enhanced by the fluorapatite surfaces. This suggested
      a combined stimulating effect of endothelial cells and fluorapatite surfaces on
      the enhanced mineralization of ASCs. Greater amounts of bFGF release by
      endothelial cells alone or cocultures with ASCs stimulated by fluorapatite
      surfaces, together with FGF pathway perturbation and bFGF treatment results,
      suggested that the FGF signaling pathway may function in this process. 

PMID- 23859379
TI  - Swift nanopattern formation of PS-b-PMMA and PS-b-PDMS block copolymer films
      using a microwave assisted technique.
AB  - Microphase separation of block copolymer (BCPs) thin films has high potential as
      a surface patterning technique. However, the process times (during thermal or
      solvent anneal) can be inordinately long, and for it to be introduced into
      manufacturing, there is a need to reduce these times from hours to minutes. We
      report here BCP self-assembly on two different systems, polystyrene-b
      polymethylmethacrylate (PS-b-PMMA) (lamellar- and cylinder-forming) and
      polystyrene-b-polydimethylsiloxane (PS-b-PDMS) (cylinder-forming) by microwave
      irradiation to achieve ordering in short times. Unlike previous reports of
      microwave assisted microphase segregation, the microwave annealing method
      reported here was undertaken without addition of solvents. Factors such as the
      anneal time and temperature, BCP film thickness, substrate surface type, etc.
      were investigated for their effect of the ordering behavior. The microwave
      technique was found to be compatible with graphoepitaxy, and in the case of the
      PS-b-PDMS system, long-range translational alignment of the BCP domains was
      observed within the topographic patterns. To demonstrate the usefulness of the
      method, the BCP nanopatterns were turned into an 'on-chip' resist by an initial
      plasma etch and these were used to transfer the pattern into the substrate. 

PMID- 23859366
TI  - Mechanistic analysis of challenge-response experiments.
AB  - We present an application of mechanistic modeling and nonlinear longitudinal
      regression in the context of biomedical response-to-challenge experiments, a
      field where these methods are underutilized. In this type of experiment, a system
      is studied by imposing an experimental challenge, and then observing its
      response. The combination of mechanistic modeling and nonlinear longitudinal
      regression has brought new insight, and revealed an unexpected opportunity for
      optimal design. Specifically, the mechanistic aspect of our approach enables the
      optimal design of experimental challenge characteristics (e.g., intensity,
      duration). This article lays some groundwork for this approach. We consider a
      series of experiments wherein an isolated rabbit heart is challenged with
      intermittent anoxia. The heart responds to the challenge onset, and recovers when
      the challenge ends. The mean response is modeled by a system of differential
      equations that describe a candidate mechanism for cardiac response to anoxia
      challenge. The cardiac system behaves more variably when challenged than when at
      rest. Hence, observations arising from this experiment exhibit complex
      heteroscedasticity and sharp changes in central tendency. We present evidence
      that an asymptotic statistical inference strategy may fail to adequately account
      for statistical uncertainty. Two alternative methods are critiqued qualitatively
      (i.e., for utility in the current context), and quantitatively using an
      innovative Monte-Carlo method. We conclude with a discussion of the exciting
      opportunities in optimal design of response-to-challenge experiments. 

PMID- 23859380
TI  - Exploring the nature of facilitating interprofessional learning: findings from an
      exploratory study.
AB  - With the growing complexity in managing multiple disease and illness-related
      problems, increased attention is being paid to the importance of
      interprofessional education (IPE) in preparing students for working
      collaboratively with different professionals. Educational activities for mixed
      groups of health professional students are increasing, and facilitation of
      learning in interprofessional student groups is now acknowledged as an essential
      part of successful interprofessional learning activities. However, little is
      known about the strategies used by facilitators with students from different
      professions, and how they promote learning. Using data obtained through an
      analysis of videos taken as part of a large study of IPE and interprofessional
      practice, this study aimed to identify the pedagogical strategies and behaviours
      of facilitators participating in seven different learning activities with health
      care students from five different professions. The data captured student
      reactions and behaviours and provided insight into the dynamics of the
      interprofessional encounters. The findings showed that facilitating groups
      involved a complex interchange of three types of interaction between facilitators
      and students: facilitator-controlled interaction, facilitator-driven interaction
      and student-driven interactions. The findings also suggest that faculty
      development programs should assist facilitators to re-examine teaching approaches
      and encourage students to assume the responsibility for discussing issues and
      collaborating with others in all their interprofessional contacts. Continuity and
      stability in faculty development activities will better prepare clinical
      educators and young professionals to become interprofessional champions.

PMID- 23859381
TI  - [Push on the research and application in technique of multimodal brain imaging].

PMID- 23859382
TI  - [Assessment of left ventricle volume filling curve with magnetic resonance
      imaging: a preliminary study].
AB  - OBJECTIVE: To conduct a preliminary study on the reliability of left ventricle
      volume filling curve through the commercial medical program Report-Card 4.0.
      METHODS: A total pf 22 normal volunteers underwent the examination. Images of
      standard 2-chamber view and short-axis view were acquired at end-expiration by
      electrocardiography-gated FIESTA CINE sequence. Then one experienced doctor
      manually contoured the endocardium during end-systole and end-diastole phases
      respectively, obtained the results of the volume of end-diastole (EDV) and end
      systole (ESV), ejection fraction (EF), stroke volume (SV) and cardiac output
      (CO), processing time and mean processing time per phase. Papillary muscle was
      not included into left ventricle volume. Another two observers utilized LV
      ANALYSIS of Report-Card, generated the left ventricle volume filling curve and
      recorded the processing time and mean processing time per phase. From the curve,
      EDV, ESV, SV, EF, CO, peak ejecting rate (PER) and peak filling rate (PFR) were
      also acquired. One observer repeated the procedures a week later. RESULTS: The
      difference of results from two methods were insignificant (P > 0.05) and the
      correlation was excellent (EDV 0.963, ESV 0.944). Intra-observer and inter
      observer variability for measurements (EDV, ESV) were assessed by Bland-Altman
      analysis and interclass correlation coefficient (0.985, 0.987, 0.959 and 0.957
      respectively). The mean processing time (179 +/- 51) s by means of manually
      contouring was significantly less than the mean processing time (331 +/- 99) s
      through REPORT-CARD 4.0 (P < 0.001). However, the mean processing time per phase
      (17 +/- 5) s by means of REPORT-CARD 4.0 was significantly less than the mean
      processing time per phase (89 +/- 26) s through manually contouring (P < 0.001).
      CONCLUSION: The reliability of left ventricle volume filling curve generated
      through Report-Card is excellent. Left ventricle volume filling curve may be a
      reliable method of further studying the functions of left ventricle.

PMID- 23859383
TI  - [In vivo labeling of rat neural progenitor cells in subventricular zone with
      superparamagnetic iron oxide for tracking of magnetic resonance imaging].
AB  - OBJECTIVE: To explore the feasibility of in vivo labeling of adult rat neural
      progenitor cells (NPCs) in subventricular zone (SVZ) with superparamagnetic iron
      oxide particles (SPIOs) for tracking of magnetic resonance imaging (MRI).
      METHODS: A total of 7 SD rats were stereotactically injected with 3 ul SPIOs (7
      mg Fe/ml) into anterior horn of right lateral ventricle and then 5-bromo-2'
      deoxyuridine (BrdU) was injected intraperitoneally once daily for 1 week. MRI was
      performed at 1, 3, 7 and 14 days post-injection. After the final MRI scan, all
      rats were transcardially perfused and their brains removed and fixed. The
      sections were processed for Prussian blue iron staining and Prussian blue plus
      BrdU immunohistochemical staining. RESULTS: In all experimental animals, SPIOs
      were predominantly located in the anterior horn of right lateral ventricle and
      partial SPIOs entered the ventricular system. A needle path and a distribution of
      SPIOs along rostral migratory stream (RMS) towards olfactory bulb (OB) were
      depicted at the sagittal view of T2(*)WI, moderate MR artifact was visible and
      SPIOs tracking NPCs were successful (success rate of 100%). The result of
      staining showed SPIOs labeling NPCs were effective. And the labeling rates were
      75.5%, 42.3%, 23.6% in SVZ, RMS and OB respectively. CONCLUSION: Effective in
      vivo labeling of adult rat NPCs in SVZ with SPIOs is feasible. And dynamical
      migration of labeling NPCs along RMS towards OB may be visualized on MRI.

PMID- 23859384
TI  - [Application of magnetic resonance diffusion weighted imaging in early ankylosing
      spondylitis].
AB  - OBJECTIVE: To evaluate the magnetic resonance diffusion-weighted imaging (DWI) in
      the detection of early ankylosing spondylitis and explore the manifestations of
      ankylosing spondylitis on whole body DWI (WB-DWI). METHODS: A total of 16
      patients with early ankylosing spondylitis (AS) and 18 patients with low back
      pain (LBP) were recruited. Subchondral bone marrow apparent diffusion coefficient
      (ADC) in bilateral ilium and sacrum along sacroiliac joints were compared. An
      independent sample t-test (SPSS 16.0, SPSS, Chicago, III) was utilized to analyze
      the ADC value differences between groups. P < 0.05 denoted statistical
      significance. The mean ADC values of focal lesions in AS patients were also
      measured. Whole body diffusion weighted imaging was performed in additional 8
      clinical confirmed AS patients and analyzed with the techniques of maximum
      intensity projection (MIP) and multiplanar reconstruction (MPR) in comparison
      with conventional MRI images to investigate the detectability of AS lesions with
      whole body DWI. RESULTS: Mean ADC values in 16 AS patients were (0.51 +/-
      0.13)*10(-3)mm(2)/s in ilium and (0.49 +/- 0.17)*10(-3)mm(2)/s in sacrum. Mean
      ADC values in 18 LBP patients were (0.32 +/- 0.06)*10(-3)mm(2)/s in ilium and
      (0.31 +/- 0.08)*10(-3)mm(2)/s in sacrum. The ADC value in AS patients were
      statistically significantly greater than those in ilium and sacrum of LBP
      patients. Whole body DWI detected abnormalities in 8 AS patients within bilateral
      sacroiliac joints and other sites corresponding to the clinical symptoms of
      patients. The mean ADC values of focal lesions of this patient cohort were (1.31
      +/- 0.38)*10(-3)mm(2)/s in sacrum and (1.18 +/- 0.27)*10(-3)mm(2)/s in ilium.
      CONCLUSION: Subchondral marrow ADC values along sacroiliac joints allow the
      differentiation of patients with early AS from LBP patients. In conjunctions with
      such post-processing techniques as MIP and MPR, WB-DWI allows a comprehensive
      assessment of AS patients to guide treatment, evaluate prognosis and follow
      therapeutic responses.

PMID- 23859385
TI  - [Normal pneumatization time of paranasal sinuses in 799 children: evaluation with
      magnetic resonance imaging].
AB  - OBJECTIVE: To evaluate the onset of initial pneumatization of paranasal sinuses
      with magnetic resonance imaging (MRI) and provides references in the diagnosis
      and treatment of pediatric paranasal sinuses disease. METHODS: The MRI images of
      paranasal sinuses were retrospectively reviewed for 799 children of 0 month to 15
      years old and the first pneumatization time of paranasal sinuses were analyzed.
      RESULTS: The ethmoidal sinuses was the first pneumatized in 100% (46/46) of
      newborn children. And 45.7% (21/46) of maxillary sinuses showed pneumatization
      during the first month of life and 97.8% (45/46) were pneumatized at 7 - 12
      months. The pneumatized sphenoid sinuses was first identified as early as 4
      months. And 86% (43/50) were pneumatized from 1 to 2 years old. Frontal sinuses
      was the last pneumatized paranasal sinuses. And 8% (4/50) of frontal sinuses were
      pneumatized at 1 - 2 years old and 97.8% (42/43) showed pneumatization at 14 - 15
      years old. CONCLUSION: MRI may be used to observe the pneumatization of paranasal
      sinuses. The initial pneumatization time of paranasal sinuses is earlier than
      previously described.

PMID- 23859386
TI  - [Breast cancer subtypes based on ER/PR and Her2 expression: comparison of MR
      imaging features].
AB  - OBJECTIVE: To evaluate the magnetic resonance (MR) imaging findings of breast
      cancer subtypes based on the profiles of ER/PR and Her2. METHODS: A retrospective
      study was conducted for 267 breast cancer subjects between February 2007 and
      January 2011. Clinicopathologic features and MR imaging findings of four subtypes
      were compared. The Chi-square (chi(2)) test, Fisher's exact test and chi(2)
      section method were employed for categorical variables. RESULTS: MR imaging
      findings:Patients with segment or linear enhancement type accounted for 25.6% in
      ER/PR(+), Her2(+) subtype group and 36.1% in ER/PR(-), Her2(+) subtype, no
      significant difference existed between them (chi(2) = 1.112, P = 0.641). But they
      were significantly higher than ER/PR(+), Her2(-) subtype group and ER/PR(-),
      Her2(-) subtype group (chi(2) = 32.793, P < 0.001; chi(2) = 14.565, P < 0.001).
      ER/PR(-), Her2(-) subtype patients accounted for 14.6% of the total breast cancer
      patients (39/267). Subjects with ER/PR(-), Her2(-) subtype were more likely to
      present unifocal (91.7%, 33/36) and mass type lesion (92.3%, 36/39). The mass
      type lesions in ER/PR(-), Her2(-) subtype group were more likely to showed smooth
      margin [58.3% (21/36), P < 0.001], very high intratumoral signal and peripheral
      hyperintense pattern on fat suppression T2-weighted imaging (P < 0.001) and early
      rim enhancement [81.5% (29/36), P < 0.001]. No significantly difference of four
      subtypes were found on number of mass, mass shape and pattern at dynamic
      enhancement imaging (chi(2) = 1.413, P = 0.713; chi(2) = 8.423, P = 0.204; chi(2)
      = 4.657, P = 0.540). CONCLUSION: Segment or linear enhancement type is
      characterized by MR imaging. Early rim enhanced mass is ER/PR(-), Her2(-) breast
      cancer. The most important characteristics of MR imaging include a smooth edge of
      breast mass, very high intratumoral signal on fat suppression T2-weighted imaging
      and peripheral hyperintense pattern.

PMID- 23859387
TI  - [Preoperative location of major language functional cerebral areas using
      functional magnetic resonance imaging].
AB  - OBJECTIVE: To design a set of functional magnetic resonance imaging (fMRI) tasks
      to activate the major Chinese language functional areas. METHODS: Eight
      volunteers and 3 patients received fMRI studies with the tasks of semantic
      judgment, word reading and listening comprehension. Brain activation map of each
      task was obtained after standard fMRI data processing. RESULTS: The fMRI
      examination with 3 tasks activated middle frontal gyrus (BA 9), Broca area and
      Wernicke area respectively. CONCLUSION: A set of fMRI examinations, including
      semantic judgment, word reading and listening comprehension, can activate the
      major Chinese language functional areas steadily and may be used as a
      preoperative localizer of language areas.

PMID- 23859388
TI  - [Prevalence and risk factors of atherosclerotic renal artery stenosis].
AB  - OBJECTIVE: To explore the prevalence and risk factors of atherosclerotic renal
      artery stenosis (ARAS) in patients undergoing coronary angiography. METHODS: A
      total of 2506 patients with suspected and known coronary heart disease (CAD) at
      our hospital underwent simultaneous coronary and renal angiography. Renal artery
      stenosis was defined as at least one of renal artery stenosis >= 50% narrowing of
      luminal diameter. The prevalence of ARAS was summarized from the results of
      angiography. And single- and multi-variable logistic regression analysis was used
      to assess the relationship between clinical characteristics and ARAS. RESULTS:
      Among them, there were 1479 males and 1027 females with a mean age of 62.7 +/-
      11.4 years. ARAS was detected in 409 patients (16.3%), including 214 (8.5%) with
      significant stenosis (>= 75%); Bilateral ARAS was detected in 98 patients (3.9%),
      including 27 (1.1%) with significant stenosis (>= 75%). Left and right ARAS were
      detected in 162 patients (6.5%) and 148 patients (5.9%) respectively, including
      84 patients (3.4%) with significant stenosis (>= 75%) in left ARAS and 72
      patients (2.9%) in right ARAS. Univariate analysis indicated that age, females,
      diabetes, hypertension, stroke, peripheral artery disease, coronary heart
      disease, renal insufficiency, dyslipidemia and hyperuricemia were the predictor
      for ARAS (P < 0.05 or 0.01). Multivariate regression analysis demonstrated that
      age >= 65 years (P = 0.025, OR = 1.358), females (P < 0.01, OR = 1.678),
      hypertension (P < 0.01, OR = 1.650), peripheral artery disease (P < 0.01, OR =
      14.678), renal insufficiency (P < 0.01, OR = 1.835), coronary heart disease
      including 3-vessel (P < 0.01, OR = 1.746) and left main coronary (P < 0.01, OR =
      3.416)disease were independent risk factors for ARAS. CONCLUSION: Renal
      angiography should be routinely performed in female patients aged >= 65 years
      with hypertension, peripheral artery disease, elevated creatinine and coronary
      heart disease, especially for 3-vessel and left main coronary disease to identify
      ARAS in time.

PMID- 23859389
TI  - [Ketamine inhalation before one-lung ventilation for perioperative lung
      protection in thoracic surgery patients].
AB  - OBJECTIVE: To explore the effects of ketamine inhalation before one-lung
      ventilation (OLV) in patients undergoing transthoracic esophagectomy for
      esophageal cancer. METHODS: Upon the approval of hospital ethic committee, 90
      American Society of Anesthesiologists grade I-II patients scheduled for elective
      trans-left-thoracic esophagectomy for esophageal cancer were randomly and single
      blindly divided into 3 groups. After intravenous anesthesia with double-lumen
      endobronchial intubation, the patients in each group received different therapies
      before OLV, i.e. inhaling ketamine 1 mg/kg in Group Ki, intravenous infusion of
      ketamine 1 mg/kg in Group Kv and inhaling normal saline 10 ml in Group C.
      Arterial blood gas analysis was performed. And (oxygen saturation) SpO2, (partial
      pressure of end-tidal carbon dioxide) PETCO2, (airway pressure) Paw and
      hemodynamic indicators were recorded at these points:before OLV (T1), OLV for 30
      min (T2), OLV for 1 h (T3), OLV for 2 h (T4), OLV ended 5 min (T5) and end of
      surgery (T6). Central venous blood was sampled at T1, T2 and 2 h after surgery
      (T7) for the determination of interleukin-6 (IL-6), interleukin-8 (IL-8) and
      soluble intercellular adhesion molecule-1 (sICAM-1) concentrations by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Serum levels of IL-6, IL-8 and sICAM
      1 in all groups increased significantly than those at previous timepoints. Serum
      levels of IL-6, IL-8 and sICAM-1 in Groups Ki and Kv were significantly lower
      than those in Group C at T7. PaO2 in Groups Ki and Kv was significantly higher
      than that in Group C at T4. Systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) in Group Kv were significantly higher than that in Groups Ki and C
      at T2-T4; HR in Group Kv was significantly higher than that in Group C at T2-T3.
      Paw in Group Kv was significantly higher than that in Group C at T2-T6.
      CONCLUSION: Inhalation and intravenous infusion of ketamine before OLV are
      equally effective in lowering the serum levels of IL-6, IL-8 and sICAM-1. And
      ultrasonic atomizing inhalation of ketamine can avoid adverse effects on airway
      pressure and circulatory system caused by an intravenous infusion of ketamine.

PMID- 23859390
TI  - [Clinical analyses of perinuclear antineutrophil cytoplasmic antibody associated
      hypertrophic pachymeningitis].
AB  - OBJECTIVE: To explore the clinical characteristics, diagnosis, treatment and
      prognosis of perinuclear antineutrophil cytoplasmic antibody (p-ANCA) associated
      hypertrophic pachymeningitis. METHODS: A retrospective study was performed for 6
      inpatients with p-ANCA associated hypertrophic pachymeningitis at our hospital
      from 2005 to 2012. RESULTS: There were 3 males and 3 females with an age range of
      52 - 68 years. The main clinical manifestations included headache and multiple
      cranial neuropathies. Erythrocyte sedimentation rate, C-reactive protein, titer
      of myeloperoxidase (MPO)-ANCA and protein in cerebrospinal fluid were uniformly
      elevated in all 6 patients during active phase while cytoplasmic(c)-ANCA was all
      negative. Head magnetic resonance imaging (MRI) enhancement scan had a high
      diagnostic sensitivity. Different parts of dura were all thickened and obviously
      enhanced. Glucocorticoid was uniformly effective. During the follow-up period, 2
      cases relapsed and received immunosuppressive agents. CONCLUSION: The disease
      should be considered in elderly patients with headache, cranial nerve injury and
      positive p-ANCA. And head MRI enhancement scan is helpful for diagnosis.

PMID- 23859391
TI  - [Pharmacoeconomic evaluation for the treatment of rheumatoid arthritis].
AB  - OBJECTIVE: To conduct pharmacoeconomic evaluations for the two therapies of
      rheumatoid arthritis (RA). METHODS: An expert survey was conducted on the cost
      and effectiveness of two RA therapies of methotrexate (MTX) alone and recombinant
      human tumor necrosis factor-alpha receptor II:IgG Fc fusion protein (rhTNFR:Fc)
      plus MTX, followed by simulation estimates, and cost-effectiveness analysis on
      the basis of pharmacoeconomic Markov model. RESULTS: MTX alone and rhTNFR:Fc plus
      MTX cost RMB 1422 Yuan and RMB13 000 Yuan respectively per treatment cycle (3
      months). Five-year Markov model showed that the incremental cost-effectiveness
      ratio of rhTNFR:Fc plus MTX was RMB 99 662 Yuan per QALY when compared with MTX
      alone. And it was lower than the threshold of willingness to pay. CONCLUSION: The
      patients with RA on the combined treatment of rhTNFR:Fc and MTX may have
      potential long-run economic advantage over those on the treatment of MTX alone.

PMID- 23859392
TI  - [Efficacy evaluation of percutaneous vertebroplasty via an extra-pedicular
      approach for osteoporotic compression fracture].
AB  - OBJECTIVE: To evaluate the effects of relieving pains and restoring vertebral
      heights of percutaneous balloon kyphoplasty by extra-pedicular approach as a
      minimally invasive treatment in patients with painful osteoporotic vertebral
      compressive fractures (OVCF). METHODS: A retrospective analysis was conducted for
      96 consecutive patients. There were 64 females and 32 males with a mean age 67
      years (range: 55 - 82). Symptomatic levels were identified by correlating their
      clinical presentations with the findings of magnetic resonance imaging (MRI). The
      interval between onset of symptoms and surgical intervention ranged from 2 days
      to 4 months. A total of 118 levels (56 thoracic, 62 lumbar) were treated in this
      cohort. Immediate and postoperative 3-month follow-up visits were conducted.
      Visual analog scale (VAS) pain scores, preoperative and postoperative anterior,
      midline vertebral heights for fractured vertebrae were measured on lateral
      radiographs to evaluate the procedural outcomes. RESULTS: There was swift pain
      relief associated with evident augmentation in weight-bearing resistance. Pain
      decreased from 8.1 to 2.1 points. Through kyphoplasty, the anterior, midline
      vertebral heights of 118 fractured vertebral bodies increased up to (75.83 +/-
      19.84)% and (71.23 +/- 21.45)% respectively. None of them had worsening of
      fracture-induced narrowing of spinal canal. No device-related major complications
      occurred. CONCLUSION: Percutaneous kyphoplasty through an extra-pedicular
      approach results in immediate clinical improvement of mobility and pain relief.
      It safely increases vertebral body height and quickly returns geriatric patients
      to higher activity levels, increased independence and better quality-of-life. And
      its short-term outcomes are excellent.

PMID- 23859393
TI  - [Analysis of obstetric outcomes for different types of placenta previa].
AB  - OBJECTIVE: To explore the maternal and perinatal outcomes for different types of
      placenta previa (PP). METHODS: A total of 343 pregnancies with PP from January
      2003 to December 2012 at our hospital were retrospectively reviewed. The general
      profiles, maternal and perinatal outcomes of different types of 325 singleton PP
      were evaluated. RESULTS: Among them, 221 pregnancies were of complete PP. There
      were partial (n = 22) and marginal (n = 82) PP. Proportions of previous vaginal
      and cesarean deliveries in women with complete and partial PP were higher than
      those with marginal PP (P < 0.05). Compared with marginal PP group, ratio of
      placenta in the uterus posterior wall prepartum hemorrhage and probability of
      blood transfusion and neonatal asphyxia were much higher in complete and partial
      PP. The gestational age at delivery and neonatal body weight with complete PP and
      partial PP marginal PP were higher than those of the other two groups (P < 0.05).
      As for the placenta adhesion, placenta accrete or postpartum hemorrhage, no
      difference existed among three groups placenta location. CONCLUSION: The
      gestational age at delivery, prepartum hemorrhage, probability of blood
      transfusion and perinatal outcome in women with PP are related with the type of
      PP. Both complete and partial PP have relatively worse outcomes. The type of PP
      has no effect on placenta adhesion, placenta accrete or postpartum hemorrhage.

PMID- 23859394
TI  - [Study of rat lumbar vertebral endplate via micro computed tomography].
AB  - OBJECTIVE: To reconstruct the 3-dimensional (3D) models of vertebral endplate and
      internal canal structure based upon the micro computed tomography (MicroCT)
      scanning data and clarify the structural characteristics and changes of bone,
      canals and lumbar vertebral endplates with advancing age in SD rats. METHODS:
      Lumbar spines from male SD rats aged 3, 9 and 16 months (n = 15 each) were
      subjected to MicroCT scan. Mimics software was used to reconstruct the 3D models
      of lumbar vertebral endplate and internal canal structure. The bone volume
      fraction (BV/TV) of endplate was measured by CTAn software. RESULTS: The rebuilt
      3D models of vertebral endplate showed that lumbar endplate was a thin layer of
      bone and the canals within vertebral endplate formed a ring-shaped canal network
      after reconstruction. Communicating branches existed between the adjacent canals.
      Every ring-shaped canal connected with trunk canals lying in the ventral and
      dorsal portions of endplate. The BV/TV of endplate in the ventral portion was
      lower than that in dorsal portion (ventral side: 79.9% +/- 7.3%; dorsal side:
      90.6% +/- 6.2%, P < 0.05) and BV/TV increased with advancing age. CONCLUSION: The
      canals within rat lumbar vertebral endplate are not haphazard, but regularly
      arrayed to form a ring-shaped network of many circular canals, communicating
      branches and ventral and dorsal trunk canals. This canal network provides
      channels for blood vessels within endplate. The ratio of older rat canals
      decreases in endplate.

PMID- 23859395
TI  - [Preliminary study of influence of bone tissue from osteonecrosis of femoral head
      on the proliferation and differentiation of canine bone marrow mesenchymal stem
      cells].
AB  - OBJECTIVE: To examine the effects of bone tissue from osteonecrosis of femoral
      head on the proliferation and differentiation of canine bone marrow mesenchymal
      stem cells in vitro culture. METHODS: A canine model of femoral head
      osteonecrosis was induced by liquid nitrogen freezing. BMSC were isolated from
      dog ilium bone marrow by a combination of gradient centrifugation and adherent
      wall culture. Different bone tissues and BMSC were cultivated indirectly in vitro
      by co-cultured in Transwell plate. According to the culture media, 3 groups were
      established: blank group (10%FBS/DMEM), control group (10%FBS/DMEM+ bone tissue
      from natural femoral head) and experimental group (10%FBS/DMEM+ bone tissue from
      osteonecrosis of femoral head). Cell proliferation was measured by methyl-thiazol
      tetrazolium (MTT) method. Cell differentiation was examined by alkaline
      phosphatase (ALP) staining and its concentration examined. Alizarin red staining
      method was used to study the calcification effects and Oil red O staining method
      was used to detect if there was fat emergence. RESULTS: As compared with the
      blank group, the proliferation in the control and experiment groups were
      significantly promoted after culturing for Days 1, 3 and 5 (P < 0.05). The
      proliferation of the experiment group was higher than the control group at Day 5
      and 7 day (P < 0.05). After a 7-day co-culturing, ALP staining was positive in
      the control and experiment groups. At Day 7 and 9, the ALP activity in culture
      fluid was in this order: control group > experiment group > blank group (P <
      0.05). Alizarin red staining show control group had the most calcium nodules
      (12.17 +/- 2.48, P < 0.05) and the number of calcium nodules in the experiment
      group was more than the blank group (P < 0.05). Oil red O staining show there was
      no fat emergence after 21 days in every group. CONCLUSION: Both natural and
      osteonecrotic bone tissue of femoral head could promoted the proliferation of
      canine BMSC and induces them osteogenic differentiation but not lipo
      differentiation, bone tissue from osteonecrosis of the femoral head had more
      competence in promoting proliferation but less capability in inducing osteogenic
      differentiation than natural bone tissue of the femoral head.

PMID- 23859396
TI  - [Act of Arc siRNA via lentivirus on the memory consolidation of amygdala-kindled
      rats].
AB  - OBJECTIVE: To explore the memory consolidation related role of gene Arc in
      amygdala-kindled rats. METHODS: A total of 60 male amygdala-kindled rats were
      divided equally into 3 groups: 0.9% sodium chloride injection, null vector
      lentivirus injection and silencing lentivirus injection. Quantitative polymerase
      chain reaction (qPCR) and Western blot were performed to confirm the silencing
      efficiency of Arc. And the passive avoidance test and Morris' water maze were
      used to test the memory consolidation ability of rats in three groups. RESULTS:
      The memory consolidation ability became significantly impaired in the Arc
      silencing group in both of passive avoidance test and water maze comparing to the
      other groups. And no significant difference existed in memory consolidation
      ability between 0.9% sodium chloride and null vector lentivirus injection groups.
      CONCLUSION: The ability of memory consolidation is impaired in Arc silencing
      amygdala-kindled rats and Arc may play a significant role in the consolidation of
      memory in amygdala-kindled rats.

PMID- 23859397
TI  - [Effects of antagonist and agonist of nicotinic acetylcholine receptors on injury
      of rat neurons induced by amyloid beta-protein].
AB  - OBJECTIVE: To explore the chronic effects of nicotinic antagonist and agonist on
      rat neurons injury induced by beta-amyloid protein. METHODS: The rat model of
      neuron injury was established by the exposure to Abeta25-35 and the intervention
      agent was either methyllycaconitine (MLA) or nicotine (Nic). And the experimental
      groups were control (distilled water), Abeta25-35, MLA (MLA and Abeta25-35) and
      Nic (Nic and Abeta25-35). Cellular viability was detected by methyl thiazolyl
      tetrazolium (MTT) chromatometry while apoptosis and necrosis were detected by
      flow cytometer. RESULTS: Compared with control, cellular viability decreased
      while the apoptotic and necrotic rates increased in Abeta25-35 group(P = 0.00).
      The values of cellular viability at (0.75 +/- 0.02) and (0.75 +/- 0.09) in
      Abeta25-35 and MLA groups respectively were significantly lower than that of Nic
      group (0.81 +/- 0.02, P = 0.01) at Day 3 and 7. No significant differences
      existed in cellular viability between Abeta25-35 and MLA groups. At Day 14, the
      differences of cellular viability were not obvious in all groups. At Day 21, cell
      viability of MLA group (0.64 +/- 0.10) was significantly higher than those of
      Abeta25-35 (0.57 +/- 0.04, P = 0.019) and Nic groups (0.56 +/- 0.04, P = 0.008).
      The apoptotic rate was lower than that of Abeta25-35 group (3.70% +/- 0.20% vs
      4.70% +/- 0.46%, P = 0.008) while the necrotic rate lower than that of Abeta25-35
      group (7.73% +/- 0.86% vs 16.30% +/- 1.05%, P = 0.00) and Nic group (16.03% +/-
      1.53%, P = 0.00). However, no significant differences existed in cellular
      viability or apoptotic and necrotic rate between Abeta25-35 and Nic groups.
      CONCLUSION: With chronic treatment, the protective effect of alpha7 nicotinic
      antagonist methyllycaconitine increases whereas that of nicotinic agonist
      nicotine decreases.

PMID- 23859398
TI  - [Neuroprotective mechanism of hydrogen sulfide after cerebral ischemia
      reperfusion in rats].
AB  - OBJECTIVE: To explore the neuroprotective mechanism of exogenous hydrogen sulfide
      after cerebral ischemia-reperfusion (I/R) in rats. METHODS: A total of 240 male
      Sprague-Dawley rats were randomly divided into 4 groups of sham-operation group
      (I), I/R model group (II), low-dose sodium hydrosulfide (NaHS) group (III) and
      high-dose NaHS group (IV) (n = 60 each). Reversible middle cerebral artery
      occlusion (MCAO) model was established by intraluminal suture. However, the rats
      of group I were operated without a blockage of middle cerebral artery. The
      occlusions in other groups were removed after 2 h. And at 20 min pre-removal,
      normal saline, 50 umol/kg NaHS, and 100 umol/kg NaHS were injected into the
      abdomens of rats in groups II, III and IV respectively. At 6 h, 24 h, 48 h and 7
      d post-reperfusion, behavioral test was performed to evaluate the neurological
      deficiency. And triphenyltetrazolium chloride (TTC) staining was used to observe
      the volume of cerebral infarction. In addition, the protein expressions of tumor
      necrosis factor-alpha (TNF-alpha) and heat shock protein 20 (HSP20) in ischemic
      cortex were measured by immunohistochemistry and Western blot. RESULTS: Compared
      with I/R group, the neurological deficiency scores and volume of cerebral
      infarction of groups III and IV significantly decreased. Furthermore, the protein
      expression of HSP20 was markedly up-regulated in the groups III and IV while
      there was a marked down-regulation of TNF-alpha after reperfusion. CONCLUSION:
      NaHS may exert anti-necrotic and anti-inflammatory function by inducing the
      expression of HSP20, inhibiting the expression of TNF-alpha and reducing the size
      of cerebral infarction so as to protect neurons after I/R injury.

PMID- 23859399
TI  - The integrated management for renal replacement therapy in Portugal.
AB  - Portugal was the first European country to introduce an integrated management of
      end-stage renal disease (IM ESRD). This new program integrates various dialysis
      services and products, which are reimbursed at a fixed rate/patient/week called
      "comprehensive price payment." This initiative restructured the delivery of
      dialysis services, the monitoring of outcomes, and the funding of renal
      replacement therapy. This article described the implementation of a new model of
      comprehensive provision of hemodialysis (HD) services and aimed to assess its
      impact on dialysis care. Quality assessments and reports of patient satisfaction,
      produced by the Ministry of Health since 2008, as well as national registries and
      reports, provided the data for this review. Indicators of HD services in all
      continental facilities show positive results that have successively improved
      along the period of 2009-2011, in spite of an average annual growth of 3% of the
      population under HD treatment. Mortality rates for HD patients were 12.7%, 12%,
      and 11%, respectively in 2009, 2010, and 2011; annual hospitalization rates were
      4.9%, 3.8%, and 4.4% for the same years; key performance indicators showed
      averages above the reference values such as hemoglobin, serum phosphorus, eKt/V,
      water quality, number of days of hospitalization per patient per year, and number
      of weekly dialysis sessions. The financing analysis of IM ESRD demonstrates a
      sustained control of global costs, without compromising quality. The IM ERSD
      program is an innovative and quality-driven approach that benefits both dialysis
      patients and providers, contributing toward the rationalization of service
      provision and the efficient use of resources. 

PMID- 23859400
TI  - Coacervates of lactotransferrin and beta- or kappa-casein: structure determined
      using SAXS.
AB  - Lactotransferrin (LF) is a large globular protein in milk with immune-regulatory
      and bactericidal properties. At pH 6.5, LF (M = 78 kDa) carries a net
      (calculated) charge of +21. beta-Casein (BCN) and kappa-casein (KCN) are part of
      the casein micelle complex in milk. Both BCN and KCN are amphiphillic proteins
      with a molar mass of 24 and 19 kDa and carry net charges of -14 and -4,
      respectively. Both BCN and KCN form soap-like micelles, with 40 and 65 monomers,
      respectively. The net negative charges are located in the corona of the micelles.
      On mixing LF with the caseins, coacervates are formed. We analyzed the structure
      of these coarcervates using SAXS. It was found that LF binds to the corona of the
      micellar structures, at the charge neutrality point. BCN/LF and KCN/LF ratios at
      the charge neutrality point were found to be ~1.2 and ~5, respectively. We think
      that the findings are relevant for the protection mechanism of globular proteins
      in bodily fluids where unstructured proteins are abundant (saliva). The complexes
      will prevent docking of enzymes on specific charged groups on the globular
      protein.

PMID- 23859401
TI  - Covalent bonding: the fundamental role of the kinetic energy.
AB  - This work addresses the continuing disagreement between two prevalent schools of
      thought concerning the mechanism of covalent bonding. According to Hellmann,
      Ruedenberg, and Kutzelnigg, a lowering of the kinetic energy associated with
      electron delocalization is the key stabilization mechanism. The opposing view of
      Slater, Feynman, and Bader has maintained that the source of stabilization is
      electrostatic potential energy lowering due to electron density redistribution to
      binding regions between nuclei. Despite the large body of accurate quantum
      chemical work on a range of molecules, the debate concerning the origin of
      bonding continues unabated, even for H2(+), the simplest of covalently bound
      molecules. We therefore present here a detailed study of H2(+), including its
      formation, that uses a sequence of computational methods designed to reveal the
      relevant contributing mechanisms as well as the spatial density distributions of
      the kinetic and potential energy contributions. We find that the electrostatic
      mechanism fails to provide real insight or explanation of bonding, while the
      kinetic energy mechanism is sound and accurate but complex or even paradoxical to
      those preferring the apparent simplicity of the electrostatic model. We further
      argue that the underlying mechanism of bonding is in fact of dynamical character,
      and analyses that focus on energy do not reveal the origin of covalent bonding in
      full clarity. 

PMID- 23859402
TI  - Molecular biodiversity of mycotoxigenic fungi that threaten food safety.
AB  - Fungal biodiversity is one of the most important contributors to the occurrence
      and severity of mycotoxin contamination of crop plants. Phenotypic and metabolic
      plasticity has enabled mycotoxigenic fungi to colonize a broad range of
      agriculturally important crops and to adapt to a range of environmental
      conditions. New mycotoxin-commodity combinations provide evidence for the ability
      of fungi to adapt to changing conditions and the emergence of genotypes that
      confer enhanced aggressiveness toward plants and/or altered mycotoxin production
      profiles. Perhaps the most important contributor to qualitative differences in
      mycotoxin production among fungi is variation in mycotoxin biosynthetic genes.
      Molecular genetic and biochemical analyses of toxigenic fungi have elucidated
      specific differences in biosynthetic genes that are responsible for intra- and
      inter-specific differences in mycotoxin production. For Aspergillus and Fusarium,
      the mycotoxigenic genera of greatest concern, variation in biosynthetic genes
      responsible for production of individual families of mycotoxins appears to be the
      result of evolutionary adaptation. Examples of such variation have been reported
      for: a) aflatoxin biosynthetic genes in Aspergillus flavus and Aspergillus
      parasiticus; b) trichothecene biosynthetic genes within and among Fusarium
      species; and c) fumonisin biosynthetic genes in Aspergillus and Fusarium species.
      Understanding the variation in these biosynthetic genes and the basis for
      variation in mycotoxin production is important for accurate assessment of the
      risks that fungi pose to food safety and for prevention of mycotoxin
      contamination of crops in the field and in storage. 

PMID- 23859403
TI  - A review on traditional Turkish fermented non-alcoholic beverages: microbiota,
      fermentation process and quality characteristics.
AB  - Shalgam juice, hardaliye, boza, ayran (yoghurt drink) and kefir are the most
      known traditional Turkish fermented non-alcoholic beverages. The first three are
      obtained from vegetables, fruits and cereals, and the last two ones are made of
      milk. Shalgam juice, hardaliye and ayran are produced by lactic acid
      fermentation. Their microbiota is mainly composed of lactic acid bacteria (LAB).
      Lactobacillus plantarum, Lactobacillus brevis and Lactobacillus paracasei subsp.
      paracasei in shalgam fermentation and L. paracasei subsp. paracasei and
      Lactobacillus casei subsp. pseudoplantarum in hardaliye fermentation are
      predominant. Ayran is traditionally prepared by mixing yoghurt with water and
      salt. Yoghurt starter cultures are used in industrial ayran production. On the
      other hand, both alcohol and lactic acid fermentation occur in boza and kefir.
      Boza is prepared by using a mixture of maize, wheat and rice or their flours and
      water. Generally previously produced boza or sourdough/yoghurt are used as
      starter culture which is rich in Lactobacillus spp. and yeasts. Kefir is prepared
      by inoculation of raw milk with kefir grains which consists of different species
      of yeasts, LAB, acetic acid bacteria in a protein and polysaccharide matrix. The
      microbiota of boza and kefir is affected from raw materials, the origin and the
      production methods. In this review, physicochemical properties, manufacturing
      technologies, microbiota and shelf life and spoilage of traditional fermented
      beverages were summarized along with how fermentation conditions could affect
      rheological properties of end product which are important during processing and
      storage. 

PMID- 23859404
TI  - PI3Kgamma contributes to MEK1/2 activation in oxidative glutamate toxicity via
      PDK1.
AB  - The role of phosphoinositide 3-kinase (PI3K) in oxidative glutamate toxicity is
      not clear. Here, we investigate its role in HT22 mouse hippocampal cells and
      primary cortical neuronal cultures, showing that inhibitors of PI3K, LY294002,
      and wortmannin suppress extracellular hydrogen peroxide (H2O2) generation and
      increase cell survival during glutamate toxicity in HT22 cells. The mitogen
      activated protein kinase kinase (MEK) inhibitor U0126 also reduced glutamate
      induced H2O2 generation and inhibited phosphorylation of extracellular signal
      regulated kinase (ERK) 1/2. LY294002 was seen to abolish phosphorylation of both
      ERK1/2 and Akt. A small interfering RNA (siRNA) study showed that PI3Kbeta and
      PI3Kgamma, rather than PI3Kalpha and PI3Kdelta, contribute to glutamate-induced
      H2O2 generation and cell death. PI3Kgamma knockdown also inhibited glutamate
      induced ERK1/2 phosphorylation, whereas transfection with the constitutively
      active form of human PI3Kgamma (PI3Kgamma-CAAX) triggered MEK1/2 and ERK1/2
      phosphorylation and H2O2 generation without glutamate exposure. This H2O2
      generation was reduced by inhibition of MEK. Transfection with kinase-dead 3
      phosphoinositide-dependent protein kinase 1 (PDK1-KD) reduced glutamate-induced
      ERK1/2 phosphorylation and H2O2 generation. Accordingly, cotransfection of cells
      with PDK1-KD and PI3Kgamma-CAAX suppressed PI3Kgamma-CAAX-triggered ERK1/2
      phosphorylation and H2O2 generation. These results suggest that activation of
      PI3Kgamma induces ERK1/2 phosphorylation, leading to extracellular H2O2
      generation via PDK1 in oxidative glutamate toxicity.

PMID- 23859405
TI  - DNA interstrand cross-link repair: understanding role of Fanconi anemia pathway
      and therapeutic implications.
AB  - Interstrand cross-links (ICLs) are extremely toxic DNA lesions that prevent DNA
      double-helix separation due to the irreversible covalent linkage binding of some
      agents on DNA strands. Agents that induce these ICLs are thus widely used as
      chemotherapeutic drugs but may also lead to tumor growth. Fanconi anemia (FA) is
      a rare genetic disorder that leads to ICL sensitivity. This review provides
      update on current understanding of the role of FA proteins in repairing ICLs at
      various stages of cell cycle. We also discuss link between DNA cross-link
      genotoxicity caused by aldehydes in FA pathway. Besides this, we summarize
      various ICL agents that act as drugs to treat different types of tumors and
      highlight strategies for modulating ICL sensitivity for therapeutic interventions
      that may be helpful in controlling cancer and life-threatening disease, FA. 

PMID- 23859406
TI  - Complex interactions between host and environment in allergic diseases and the
      roles of integrative management.

PMID- 23859407
TI  - Moisturizers for patients with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common chronic inflammatory skin disease with
      epidermal barrier defects which leads to dry skin that is easily disturbed by
      external exacerbating factors. It is now well established that moisturizers play
      an important role in preventing skin inflammation in AD, including reducing the
      amount of topical corticosteroid use. Thus, the use of moisturizers is currently
      recognized as one of standard treatment for AD. This review summarizes the role
      and classification of moisturizers. We also review some ingredients that are
      commonly added in moisturizers which are claimed to have an anti-inflammatory
      effects in AD. 

PMID- 23859408
TI  - Influence of cell isolation method on the optimization of CD4+ T cell expansion
      using anti-CD3/CD28 coated beads.
AB  - BACKGROUNDS: Activation of CD4+ T lymphocytes with anti-CD3/CD28 coated magnetic
      beads promotes intrinsic resistance to HIV as well as cell expansion. The propose
      of this study is to define the optimal cell isolation protocol for expansion of
      CD4+ T lymphocytes by using anti-CD3/CD28 coated bead stimulation with an
      ultimate goal of using these cells for adoptive immunotherapy. METHODS: CD4+ T
      cells were isolated from healthy donor blood samples using three different
      methods including immunorosette formation, negative selection and CD8 depletion
      using immunomagnetic beads. These cells were activated with anti-CD3/CD28 coated
      beads at a bead to cell ratio of 1:1 and cell expansion was carried for 3 weeks.
      Cell numbers, cell viability and phenotypic characterization were determined by
      trypan blue exclusion and flow cytometry. RESULTS: Purified CD4+ T lymphocytes
      which were isolated via immunorosette formation can be expanded up to 1000-fold
      within 3 weeks with high viability (90%and high purity of CD4+ T lymphocytes
      (>95%). However, cell expansion from purified CD4+ T lymphocytes which were
      isolated by negative selection and CD8-depletion provided approximately 300-fold
      expansion. CONCLUSIONS: The results demonstrate that purified CD4+ T lymphocytes
      from immunorosette formation provided the highest CD4+ T lymphocyte expansion
      when stimulated with anti-CD3/CD28 coated beads. This method can be used to
      obtain a large number of expanded CD4+ T cells for adoptive immunotherapy.

PMID- 23859409
TI  - Non-encapsulated Trichinella spp., T. papuae, diminishes severity of DSS-induced
      colitis in mice.
AB  - BACKGROUND: Helminths use various mechanisms to avoid host immunity and protect
      themselves from being eliminated. Despite evading host immune responses,
      immunosuppression and regulation mechanisms elicit functions that diminish the
      adverse effects of unrelated inflammatory diseases. OBJECTIVE: We investigated
      whether helminthic infections can ameliorate inflammatory diseases. METHODS: Mice
      were infected with Trichinella papuae and then subjected to induced colitis
      through the oral administration of dextran sulfate sodium (DSS). Macroscopic and
      microscopic examinations measured weight loss, stool consistency, gross bleeding,
      colon length, and tissue inflammation. In addition, cytokine expression was
      observed in colon tissue by SYBR real-time RT-PCR to investigate the Th1, Th2,
      and regulatory cytokines. RESULT: The results showed that T. papuae infection
      decreased the severity of DSS-inducedcolitis, including weight loss, bloody
      diarrhea, shortening of colon, and colon tissue damage in mice (p <0.05). The
      expression level of IL-4 was high in the colons of DSS-treated mice without
      helminthic infection, while infected mice with DSS treatment had lower IL-4
      levels (p <0.05). Uninfected DSS-treated mice failed to produce IL-10 mRNA in
      colon tissue, which may cause more severe colitis. In contrast, prior T. papuae
      infection DSS-treated mice had IL-10 levels in the colon significant lower than
      the normal and infected control groups. CONCLUSION: Our data provide the evidence
      that prior T. papuae infection can ameliorate DSS-induced colitis in mice and may
      be considered for a novel therapeutic strategy against immunological diseases in
      the future.

PMID- 23859410
TI  - Wasp venom allergy: effect of anti-IgE antibody on wasp venom anaphylaxis in a
      mouse model.
AB  - BACKGROUND: Although anti-IgE antibody (Ab) therapy was recently shown to be
      effective in patients with bronchial asthma, no study has reported the effect of
      IgE therapy in the prevention of wasp venom anaphylaxis. In this study, we used a
      mouse model of wasp venom allergy to investigate the effect of anti-IgE Ab on
      wasp venom anaphylaxis. METHODS: We developed a mouse model of wasp venom allergy
      by intraperitoneally (i.p.) injecting wasp venom into BALB/c mice twice on
      experimental day (day) 0 and 7. On day 20, a group of mice received an i.p.
      injection of mouse anti-IgE Ab as a pretreatment, and another group received rat
      anti-IgG1 Ab. On day 21, the animals were challenged by i.p. injection of wasp
      venom, and 30 min later, body temperature was measured and serum levels of
      leukotriene (LT) B4 and LTC4 were determined using enzyme immunoassay. RESULTS:
      The body temperature of mice treated with anti-IgE Ab and controls before and
      after wasp venom challenge was 37.8+/-0.2 vs 37.7+/- 0.3 degrees C before
      challenge and 37.8+/-0.2 vs 37.1+/- 0.3 degrees C after challenge, respectively,
      showing that anti-IgE Ab treatment significantly prevented body temperature from
      falling (p <0.05). Furthermore, anti-IgE Ab treatment reduced total serum IgE
      levels in the treated mice (42.2+/-15.9 pg/ml), compared with controls (105.9+/
      23.1 pg/ml, p <0.05), and inhibited the secretion of LTC4 in the treated mice
      (32.0+/-18.8 pg/ml), but not in the controls (162.4+/-12.4 pg/ml, p <0.05),
      following challenge with wasp venom. CONCLUSION: The results of the present study
      indicate that anti-IgE Ab treatment is an effective preventive measure against
      wasp venom-induced anaphylaxis.

PMID- 23859411
TI  - The study of the ratio and distribution of Th17 cells and Tc17 cells in asthmatic
      patients and the mouse model.
AB  - BACKGROUND: Whether CD8+ IL-17-producing T cells, namely Tc17 cells, play a role
      in asthma has not been determined. The aim of this study was to evaluate and
      compare the frequency of peripheral blood Th17 cells and Tc17 cells in asthmatic
      patients. In addition, the number, ratio and distribution of Th17 cells and Tc17
      cells in the lung tissue and splenocytes of asthmatic mice were also
      investigated. METHODS: Th17 and Tc17 cells in the peripheral blood samples of
      asthmatic patients and in murine spleens were detected by flow cytometric
      analysis. Th17 and Tc17 cells in murine lung tissues were detected by double
      immuno-fluorescence stain. IL-17A levels in murine bronchoalveolar lavage were
      detected by ELISA. RESULTS: The result of the flow cytometric analysis showed the
      percentage of Th17 cells among CD3+ T cell populations in patients with asthma
      was higher than that in healthy controls (P < 0.01), The percentage of Tc17 cells
      was also higher (P < 0.05). The percentages of Th17 and Tc17 cells in asthmatic
      mice were both much higher than that in control animals (P < 0.01). Frozen
      sections of lung tissue showed that the number of Th17 cells and Tc17 cells in
      the asthma group were all significantly higher than in the control group (P <
      0.01). CONCLUSIONS: Our findings suggest a functional disequilibrium of Th17 and
      Tc17 cell subsets in asthma that may contribute to the inflammatory process and
      provide novel insights into a hypothetical driving role of those cells in disease
      pathogenesis.

PMID- 23859412
TI  - CD64 expression on monocytes in children with adenoid hypertrophy.
AB  - OBJECTIVE: Adenoids with obstructive hypertrophy (AH) are considered to be one of
      the most ancient and common problems in Paediatrics. This study aimed at
      investigating the expression of CD 64 on monocytes in children who had to undergo
      adenoidectomy. METHODS: Therefore, 66 children (24 females, 42 males, mean age
      4.9 years), affected by AH and requiring adenoidectomy (54%) or adeno
      tonsillectomy (46%) were consecutively enrolled into the study. Moreover, 30
      healthy children (11 females, 19 males, mean age 11.2 years) were enrolled in
      this study as controls. CD64 expression on monocytes was measured. RESULTS:
      Children with severe AH had higher CD64 values than children with AH size 3 and
      controls. CONCLUSIONS: This preliminary study shows that CD64 expression on
      monocytes may be associated with severe AH, suggesting a more intense immune
      activation in these subjects.

PMID- 23859413
TI  - Factors affecting readmission for acute asthmatic attacks in children.
AB  - BACKGROUND: Readmission following acute asthmatic attack has an impact on
      children's quality of life and the cost of hospitalization. The objective of this
      study was to define the risk factors associated with readmission following acute
      asthmatic attacks in children. METHODS: This is a retrospective case-control
      study in children who were admitted because of acute asthmatic attacks at the
      Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok,
      Thailand. The admissions were classified into 2 groups, admission and readmission
      within one-month to one-year after the first admission. The medical records were
      reviewed and the factors that might affect readmission were evaluated. RESULTS:
      Seventy six children, 49 males and 27 females, were included. There were 56
      children who were admitted only once and 20 children who were readmitted. The 1
      year readmission rate for children with asthma was 26.3 %. The risk factors which
      made readmission more likely were a parental history of allergic disease (Odd
      Ratio, OR, = 3.17; 95% CI 1.10-9.10), a history of Intensive Care Unit (ICU)
      admission (OR 29.62; 95% CI 3.35-262.18), methylprednisolone usage during the 1st
      admission (OR 8.33; 95% CI 2.46-28.19) and the level of asthma control. Increased
      risk of readmission was found in partly controlled asthma (OR 4.83; 95% CI 1.24
      18.88) and uncontrolled asthma (OR 29; 95% CI 2.25-373.77). The factor that
      decreased the chances of readmission was a history of influenza vaccination (OR
      0.24; 95% CI 0.16-0.36). CONCLUSION: A history of ICU admission at the first
      admission and the level of asthma control (partly controlled and uncontrolled
      according to Global of Initiative for Asthma guideline) increased the chances of
      readmission while influenza vaccination reduced the chances of readmission.

PMID- 23859414
TI  - The effect of six-weeks of sauna on treatment autonomic nervous system, peak
      nasal inspiratory flow and lung functions of allergic rhinitis Thai patients.
AB  - BACKGROUND: Allergic rhinitis is a chronic respiratory disease. Sympathetic
      hypofunction has been identified in allergic rhinitis patients. OBJECTIVE: To
      investigate the effects of six weeks of repeated sauna treatment on the autonomic
      nervous system, peak nasal inspiratory flow (PNIF) and lung functions in Thai
      patients with allergic rhinitis. METHODS: Subjects were diagnosed with allergic
      rhinitis clinically by an attending physician based on history, physical
      examination and positive reactions to a skin prick test. Subjects were randomly
      assigned to two groups. Controlsubjects received education and maintained a
      normal life. The sauna group received sauna treatment over a six-week period, 3
      days per week, with 6 sets of 5 minutes per set per day, totaling 30 minutes.
      Each 5 minute set alternated with a 5 minute period of rest. Heart rate
      variability (HRV), peak nasal inspiratory flow and lung function were measured at
      the beginning and after three and six weeks of sauna treatment. The HRV
      measurement is composed of three components, including low frequency (indicating
      sympathetic function in normal units or n.u.), high frequency (indicated
      parasympathetic function in n.u.), and the ratio of LF/HF (indicating the balance
      of the autonomic system). RESULTS: Twenty-six allergic rhinitis patients, 12
      males and 14 females participated in this study, 13 in the control group and 13
      in the sauna treatment group; there were 6 males in each group. Baseline
      characteristics for the control and sauna treatment groups were comparable. There
      were significant changes in the HRV after six weeks of sauna treatment. The high
      frequency component was significantly lower in sauna treatment group (51.8 vs
      35.4), while the low frequency component and LF/HF ratio were significantly
      higher in sauna treatment group than in the control group (48.1 vs 64.5 and 0.9
      vs 2.5, respectively). The PNIF and the forced expiratory volume in one second,
      or FEV1, were also significantly higher in sauna treatment group (103.0 vs 161.9
      and 80.1 vs 95.6, respectively). CONCLUSION: The six weeks of repeated sauna
      treatment can increase sympathetic activity, PNIF, and FEV1 in Thai patients with
      allergic rhinitis.

PMID- 23859415
TI  - Determining factors of patient compliance to treatment in allergic rhinitis.
AB  - BACKGROUND: Compliance with prescribed treatment is essential for reducing costs
      of health care and improving efficacy of treatment in patients with allergic
      rhinitis. OBJECTIVE: To evaluate the extent of compliance and identify predictive
      factors and risk profiles for patient noncompliance with the therapeutic
      regiments of sublingual immunotherapy and H1-antihistamines. METHODS: In this
      retrospective study we analysed data from two non-interventional studies: one
      study with a total of 42,111 patients taking H1-antihistamines and one study with
      354 patients receiving sublingual immunotherapy. Both studies were approved by
      the local ethics committees and competent authorities. By performing univariate
      and multivariate logistic regression analysis we calculated odds ratios with a
      95% confidence interval for given characteristics. RESULTS: There was a
      compliance rate of 79.6% with the administration of sublingual immunotherapy.
      Factors associated with compliance were severe nasal, eye and airways symptoms,
      and strong impairment in social and work life. Compliance with the intake of H1
      antihistamines was 98%. Patients with a concomitant disease, especially with a
      bronchialasthma or a psychiatric disorder had higher odds for being non
      compliant. CONCLUSION: Compliance with intake of sublingual immunotherapy and H1
      antihistamines is high. However, our findings point out that patients with
      characteristics such as a comorbid bronchial asthma or mild symptoms have higher
      odds for noncompliance and require attentive monitoring to reduce healthcare
      costs and morbidity.

PMID- 23859416
TI  - Factors associated with cord blood IgE levels.
AB  - BACKGROUND: The cord blood IgE level is thought to be a predictor of allergic
      disorders in childhood. It is not well understood how this marker is influenced
      by the fetal environment, such as maternal, paternal, placenta, and fetal
      characteristics. OBJECTIVE: We aimed to investigate the association between cord
      blood IgE levels and various genetic and environmental factors. METHODS: This was
      a cross-sectional study including a total of 181 neonates and their mothers. A
      questionnaire asking about demographic data, delivery characteristics, maternal
      past medical history and information on exposure to known environmental allergens
      was distributed to pregnant women. Blood samples from them and neonatal cord
      blood samples were taken at the same time for IgE assay. RESULTS: By univariate
      analysis we found an association between cord blood IgE levels and higher number
      of previous pregnancies, delivery season, type of delivery, history of allergy
      during pregnancy, but not the type of allergic disease and history of allergic
      disease before pregnancy, were associated with elevated cord blood IgElevels. The
      maternal blood level of IgE was correlated with its level in cord blood. By
      multivariate analysis, the number of previous pregnancies, the type and season of
      delivery and a history of allergy during pregnancy and maternal age and blood IgE
      levels were variables which had a significant association with cord blood IgE
      levels. CONCLUSION: Among the evaluated factors, the presence of any kind of
      allergic disorder in the mother or her family and elevated maternal blood IgE
      level are associated with the cord blood IgE of the child. Maternal age and
      smoking, neonatal gender, type of delivery, season of birth and parity are
      probable predictors.

PMID- 23859417
TI  - Rocuronium anaphylaxis in a 3-year-old girl with no previous exposure to
      neuromuscular blocking agents.
AB  - During the perioperative period, anaphylactic reactions rarely occur.
      Neuromuscular blocking agents (NMBAs) are responsible for 60-70% of perioperative
      anaphylactic reactions. This case, we report a case of rocuronium-induced
      anaphylaxis in a 3-year-old girl with no previous exposure to NMBAs. This case
      cautions and informs practitioners that an IgE-mediated anaphylactic reaction
      with rocuronium is possible even in young children with no previous exposure to
      NMBAs. 

PMID- 23859418
TI  - X-linked chronic granulomatous disease in a male child with an X-CGD carrier,
      Klinefelter brother.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary
      immunodeficiency (PID) caused by a dysfunctional respiratory burst enzyme NADPH
      oxidase. The concurrence of Klinefelter's Syndrome (KS) and CGD would be
      extremely rare. OBJECTIVE: We describe the study of a family where the youngest
      male child had X-linked CGD (X-CGD) while his older brother was both an X-CGD
      carrier and a Klinefelter. METHODS: Flow cytometry was used to study respiratory
      burst and gp91-phox expression, while genetic investigation was done by RT-PCR,
      PCR and X-chromosome short tandem repeat (X-STR) analysis. RESULTS: The
      Dihydrorhodamine (DHR) assay showed the patient's neutrophils failed to produce a
      respiratory burst, while both the mother and an older brother showed a bimodal
      response. gp91-phox expression was absent in the patient's neutrophils, and
      bimodal in the mother's and brother's neutrophils. The patient's cDNA showed a
      C>T change at nucleotide 676 of the CYBB gene. The same change was seen in the
      patient's gDNA, while the brother and mother were heterozygous, with C and T, in
      this position. The c.676C>T is a nonsense mutation that leads to premature
      termination of the gp91-phox protein. The brother karyotyped as 47, XXY and X
      chromosome analysis showed that he had inherited both his mother's X chromosomes.
      CONCLUSIONS: This study showed that the patient had gp91-phox deficient CGD while
      his older brother was a CGD carrier and a Klinefelter, who had inherited both his
      mother's X chromosomes. This is the first report of such a concurrence in an
      individual, and argues for family members to be included in PID studies.

PMID- 23859420
TI  - The paradox of the binomial Ixodes ricinus activity and the observed unimodal
      Lyme borreliosis season in Hungary.
AB  - The change of ambient temperature plays a key role in determining the run of the
      annual Lyme season. Our aim was to explain the apparent contradiction between the
      annual unimodal Lyme borreliosis incidence and the bimodal Ixodes ricinus tick
      activity run--both observed in Hungary--by distinguishing the temperature
      dependent seasonal human and tick activity, the temperature-independent factors,
      and the multiplicative effect of human outdoor activity in summer holiday, using
      data from Hungary in the period of 1998-2012. This separation was verified by
      modeling the Lyme incidence based on the separated factors, and comparing the run
      of the observed and modeled incidence. We demonstrated the bimodality of tick
      season by using the originally unimodal Lyme incidence data. To model the outdoor
      human activity, the amount of camping guest nights was used, which showed an
      irregular run from mid-June to September. The human outdoor activity showed a
      similar exponential correlation with ambient temperature to that what the
      relative incidence did. It was proved that summer holiday has great influence on
      Lyme incidence.

PMID- 23859419
TI  - Energy content and amino acid digestibility in hulled and dehulled corn and the
      performance of weanling pigs fed diets containing hulled or dehulled corn.
AB  - Three experiments were conducted to determine the digestible (DE) and
      metabolizable energy (ME) content (Exp. 1), the apparent (AID) and standardised
      ileal digestibility (SID) of amino acids (AA) (Exp. 2) in hulled and dehulled
      corn and the performance of weanling pigs fed diets containing hulled or dehulled
      corn (Exp. 3). In Exp. 1, 18 growing barrows (19.8 +/- 0.9 kg) were fed a rice
      soybean meal basal diet or two experimental diets. The two experimental diets
      were formulated to contain 38.6% hulled or dehulled corn which replaced 40% of
      the energy supplied by rice, soybean meal and lysine to determine the energy
      content as well as the apparent total tract digestibility (ATTD) of nutrients and
      energy of hulled and dehulled corn using the difference method. There were no
      differences in the DE (15.9 MJ/kg vs. 16.3 MJ/kg) and ME (15.6 MJ/kg vs. 15.6
      MJ/kg) content in hulled and dehulled corn, respectively, but the ATTD of dry
      matter (DM; 92.5% vs. 88.9%) and organic matter (OM; 93.9% vs. 89.8%) were higher
      in dehulled corn than hulled corn (p < 0.01). In Exp. 2, 24 growing barrows (28.0
      +/- 1.6 kg) were fitted with a T-cannula in the distal ileum, allotted to one of
      the four diets with six pigs fed each diet. The four diets comprised of the basal
      diet and the two experimental diets from Exp. 1 as well as a nitrogen-free diet
      that was used to measure the basal endogenous losses of crude protein (CP) and
      AA. Results from Exp. 2 indicate that there is no improvement of the AID or SID
      of CP and AA in dehulled corn compared with hulled corn. In Exp. 3, 72 piglets
      weaned at the age of 35 d (8.3 +/- 1.2 kg) were allotted to two diets based on
      hulled or dehulled corn and formulated to contain equal quantities of ME and SID
      of AA. The ATTD of DM, OM and gross energy were higher (p < 0.01) in pigs fed
      diets containing dehulled corn than those fed diets containing hulled corn.
      However, performance of pigs fed diets containing hulled or dehulled corn was not
      different. In conclusion, dehulled corn increased nutrient digestibility, but did
      not improve pig performance. Therefore, there does not appear to be any
      justification for the routine inclusion of dehulled corn in diets fed to weaned
      pigs. 

PMID- 23859421
TI  - Spectral signatures of viewing a needle approaching one's body when anticipating
      pain.
AB  - When viewing the needle of a syringe approaching your skin, anticipation of a
      painful prick may lead to increased arousal. How this anticipation is reflected
      in neural oscillatory activity and how it relates to activity within the
      autonomic nervous system is thus far unknown. Recently, we found that viewing
      needle pricks compared with Q-tip touches increases the pupil dilation response
      (PDR) and perceived unpleasantness of electrical stimuli. Here, we used high
      density electroencephalography to investigate whether anticipatory oscillatory
      activity predicts the unpleasantness of electrical stimuli and PDR while viewing
      a needle approaching a hand that is perceived as one's own. We presented video
      clips of needle pricks and Q-tip touches, and delivered spatiotemporally aligned
      painful and nonpainful intracutaneous electrical stimuli. The perceived
      unpleasantness of electrical stimuli and the PDR were enhanced when participants
      viewed needle pricks compared with Q-tip touches. Source reconstruction using
      linear beamforming revealed reduced alpha-band activity in the posterior
      cingulate cortex (PCC) and fusiform gyrus before the onset of electrical stimuli
      when participants viewed needle pricks compared with Q-tip touches. Moreover,
      alpha-band activity in the PCC predicted PDR on a single trial level. The
      anticipatory reduction of alpha-band activity in the PCC may reflect a neural
      mechanism that serves to protect the body from forthcoming harm by facilitating
      the preparation of adequate defense responses. 

PMID- 23859422
TI  - Crash involvement of motor vehicles in relationship to the number and severity of
      traffic offenses. An exploratory analysis of Dutch traffic offenses and crash
      data.
AB  - OBJECTIVE: To establish the statistical relationship between offenses and crashes
      when the unit of analysis is the vehicle instead of the driver, to show the
      influence of the severity (e.g., minor speed offenses) on this relationship, and
      to research whether the form of this relationship is similar in different
      enforcement contexts. METHODS: An exploratory analysis was conducted using Dutch
      traffic offense and crash data. Crash data included all police-registered crashes
      involving motorized and registered vehicles in 2009; offense data included all
      non-criminal traffic offenses registered during 2005-2009 (mostly camera
      detected). Together these comprise an estimated 97 percent of all traffic
      offenses registered in this period. The analysis was done on a level of
      identified vehicles rather than persons. Vehicles involved in crashes were
      matched to vehicles involved in traffic offenses. The offense frequency
      distributions of registered crash involved vehicles and a random selection of
      vehicles was analyzed. Two comparisons were made: (1) privately owned vehicles
      versus company-owned vehicles and (2) vehicles for which only minor speed
      offenses were registered versus vehicles for which at least one major speed
      offense was registered. RESULTS: An increase in traffic offense frequency
      coincides with a stronger increase in relative crash involvement. This
      relationship was adequately described by a power function. The slightly more than
      linear increase in the crash risk for vehicles with only minor speed offenses
      suggests that minor speed offenses (<10 km/h over the limit) contributed slightly
      to crashes. This relationship was unlikely to be caused by increased distance
      traveled only. For vehicles with at least one or more major speed violation an
      approximately quadratic increase of crash risk with increasing speed offense
      frequency was found. A comparison of Dutch and Canadian data showed a much more
      progressive offense-crash relationship in the Dutch data. CONCLUSION: The crash
      involvement of vehicles increased more than linearly with the number of minor
      traffic violations. Thus, automatic detection of minor offenses bears relevance
      to safety. The substantial increase in crash rates with speed offense frequency
      for vehicles with at least one major speed violation suggests that these vehicles
      represent a specific group with a significantly increased crash risk, especially
      in the case of many minor offenses. The more progressive relationship between
      offenses and crashes in The Netherlands when compared to Canada was hypothesized
      to result from the higher intensity camera enforcement levels and less severe
      consequences in the Dutch enforcement and adjudication system.

PMID- 23859423
TI  - Metallophyte status of violets of the section Melanium.
AB  - Violets from metal-enriched soils have controversially been described as both
      heavy-metal accumulators and excluders in the literature. The present study
      solves the issue for violets of the section Melanium (zinc violets, Viola lutea
      ssp. calaminaria and V. lutea ssp. westfalica; hartsease or wild pansy, Viola
      tricolor; and mountain pansy, V. lutea). The aims were to determine the
      concentrations of heavy metals in the soil and in the roots and shoots of field
      collected plants, to evaluate the potential impact of colonisation by arbuscular
      mycorrhizal fungi on heavy-metal concentrations in the plant tissues, and to
      quantitatively define the localisation of the elements in root cross-sections.
      When these violets grow in low-metal soils, higher concentrations of the heavy
      metals were found in the roots and shoots than in the soil, whereas the opposite
      was seen in samples from high-metal soils. Under all field conditions examined,
      the roots of all of these species were colonised by arbuscular mycorrhizal fungi.
      However, V. tricolor was marginally colonised when the concentrations of Zn and P
      were higher in the soil. Determination of the spatial distribution of the
      elements in root cross-sections of these violets indicates tissue-specific
      deposition of elements within the vascular tissue, the cortex, and the
      rhizodermis. These data indicate that violets of the section Melanium are heavy
      metal excluders. 

PMID- 23859424
TI  - Partial characterization, UV-induction and photoprotective function of sunscreen
      pigment, scytonemin from Rivularia sp. HKAR-4.
AB  - Scytonemin, located in the extracellular polysaccharide sheath of some
      cyanobacterial species is considered an efficient natural photoprotectant against
      lethal doses of ultraviolet (UV) radiations. In the present study, scytonemin
      from the cyanobacterium Rivularia sp. HKAR-4 was partially characterized and
      investigated for its induction by UV radiation as well as its role in
      photoprotection. High-performance liquid chromatography (HPLC) with photodiode
      array detection studies revealed the presence of an UV-absorbing compound with
      absorption maximum at 386 nm. Based on its absorption spectrum and ion trap
      liquid chromatography/mass spectrometry (LC/MS) analysis, the compound was
      confirmed as scytonemin. In comparison to photosynthetically active radiation, a
      significant induction in the synthesis of scytonemin was found under UV-stress.
      Scytonemin also exhibited efficient photoprotective ability by detoxifying the in
      vivo reactive oxygen species (ROS) generated by UV radiation and by reducing the
      formation of thymine dimers. To the best of our knowledge this is the first
      report on the UV-screening effects of scytonemin on in vivo ROS generation and
      thymine dimer formation in any cyanobacterial strain. Based on these findings, we
      conclude that scytonemin may play a vital role in the survival and sustainability
      of cyanobacterial life in adverse environmental conditions such as under high
      solar irradiances.

PMID- 23859425
TI  - Conventional and emerging halogenated flame retardants (HFRs) in sediment of
      Yangtze River Delta (YRD) region, East China.
AB  - The occurrence and distribution of polybrominated diphenyl ethers (PBDEs) and
      eleven non-PBDE halogenated flame retardants (HFRs) were investigated through the
      collection of marine and river sediment from Yangtze River Delta (YRD), East
      China. Among them, PBDEs, decabromodiphenyl ethane (DBDPE) and 1,2-dibromo-4-(1,2
      dibromoethyl)cyclohexane (TBECH) were the three predominant HFRs with the highest
      detection frequencies in the sediment. Significant correlation between PBDEs and
      DBDPE indicated that they may have the similar emission sources. The production
      and use of DBDPE is growing rapidly and comparable concentrations between PBDEs
      and DBDPE in YRD sediment may suggest that DBDPE will likely become one of the
      major HFRs emerging in the environment in China. Of the seven detected non-PBDE
      HFRs, this is the first time that TBECH was reported in the Chinese environment
      and its predominance and prevalence in the YRD may imply its extensive use in
      these areas.

PMID- 23859426
TI  - Polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls, paraffins and
      polybrominated diphenyl ethers in marine fish species from Ebro River Delta
      (Spain).
AB  - The results of a surveillance programme on the determination of polychlorinated
      dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated
      biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and short chain
      chlorinated paraffins (SCCPs) in marine fish and shellfish species which are
      fished, commercialised and consumed in the Ebro River Delta area (NE, Spain) are
      presented. The study included the analysis of five marine fish species (sardine,
      gilthead sea bream, conger, eel and flounder) and three shellfish species (murex,
      carpet shell and mussel) collected in 2012 in five fishing harbours near to this
      area. WHO-TEQ concentrations for PCDD/Fs and dioxin like PCBs (dl-PCBs) ranged
      from 0.03 to 0.31 pg WHO-TEQ2005PCDD/Fg(-1)wetweight (ww) and from 0.02 to 3.15
      pg WHO-TEQ2005PCBg(-1)ww, respectively. All levels were below the maximum
      concentrations established by the EU Regulation. The PCBs and PCDD/Fs
      accumulation pattern found in the samples analysed showed a distribution
      typically reported for marine samples. For marker PCBs and PBDEs, concentration
      levels ranging from 929 to 57494 pg g(-1)ww and from 36.2 to 827 pg g(-1)ww were
      obtained, respectively, meanwhile for SCCPs levels were between 3.1 and 141 ng g(
      1)ww. Finally, the trends in the levels of PCDD/F and dl-PCBs found from 2006 to
      2012 in fish and shellfish species were studied. A slight decrease of PCDD/F and
      dl-PCB concentrations was found since 2006.

PMID- 23859427
TI  - Phenanthrene exposure produces cardiac defects during embryo development of
      zebrafish (Danio rerio) through activation of MMP-9.
AB  - Phenanthrene (Phe) is one of the most abundant polycyclic aromatic hydrocarbons
      in the aquatic environment as a result of human activities. It is widely accepted
      that Phe has cardiotoxic effects. Even so, knowledge concerning the mechanism(s)
      of cardiac development toxicity is still limited. In this study, we exposed
      zebrafish embryos to environmentally relevant concentrations of Phe and then
      investigated its cardiotoxic effects and the mechanism(s) involved. Some cardiac
      morphogenetic defects, which was characterized by an abnormally looped and
      enlarged heart, dilated and thinner ventricular wall, and increased interstitial
      fibrosis, were observed in the Phe treated groups. The mRNA and protein
      expression levels of matrix metalloproteinase-9 (MMP-9), as well as the MMP-9
      activity, were induced. Moreover, during co-treatment of the zebrafish embryos
      with MMP-9 inhibitor, the cardiac defects caused by Phe were attenuated. In
      addition, Phe exposure led to an up-regulation of transforming growth factor beta
      (TGF-beta), which plays a crucial role in mediating cardiac fibrosis. Taken
      together, our data indicated that the exposure to Phe of zebrafish embryos
      disrupted normal cardiac development, and that the cardiac defects induced by Phe
      were mediated by the MMP-9, while TGF-beta was also involved in these cardiac
      defects. 

PMID- 23859428
TI  - Observational follow-up of the PROactive study: a 6-year update.
AB  - AIMS: The PROactive study investigated pioglitazone for secondary prevention of
      macrovascular events in type 2 diabetes mellitus. Pioglitazone showed a 10% (non
      significant) relative risk (RR) reduction for the primary composite endpoint and
      a significant 16% reduction for the main secondary endpoint (death, myocardial
      infarction, stroke) after a mean 34.5 months. There was no difference in
      cumulative malignancy incidence, but an imbalance in bladder malignancies
      (pioglitazone 14, placebo 5). We present a pre-specified 6-year interim analysis
      of a 10-year observational follow-up. METHODS: Any patient completing PROactive
      was eligible. No study treatments were provided. A Cox proportional hazard model
      compared non-adjudicated macrovascular events (same endpoints as PROactive
      excluding acute coronary syndrome) based on original randomization. Malignancies
      were compared using conventional RR ratios. RESULTS: Of 5238 randomized patients,
      3599 (74%) entered the follow-up. For the follow-up (mean 5.8 years) or combined
      double-blind and follow-up periods (<=9.5 years, mean 8.7), there were no
      statistically significant differences in primary or main secondary endpoints. For
      the combined period, a similar percentage of patients had any diagnosed
      malignancy (RR = 1.05, 95% CI [0.89, 1.24]) or bladder malignancy (RR = 1.06, 95%
      CI [0.59, 1.89]) in the pioglitazone and placebo groups. There were fewer cases
      of bladder malignancy with pioglitazone (15 [0.6%] vs. 19 [0.7%] for placebo) for
      the combined period when events diagnosed in the first 365 days were excluded,
      and fewer cases for the follow-up period alone (10 [0.5%] vs. 17 [1.0%] for
      placebo). Further analyses of pioglitazone use (including use during follow-up)
      found no significant difference in bladder malignancies between any and no
      pioglitazone use for the combined period. CONCLUSIONS: These data suggest that
      improved macrovascular outcomes seen with pioglitazone subside without continued
      pioglitazone treatment. The double-blind period bladder cancer imbalance did not
      persist in follow-up.

PMID- 23859430
TI  - Pharmacotherapy of bipolar II disorder during and after pregnancy.
AB  - OBJECTIVES: The objective of this study was to evaluate the pharmacotherapy of
      bipolar II disorder during pregnancy and the postpartum period. METHODS: The use
      of psychotropic drugs and recurrence risk during and after pregnancy was studied
      in a prospective, observational study of 37 women with bipolar II disorder.
      RESULTS: During pregnancy the majority of participants (54.0%) were not on any
      psychotropic medication, approximately one third (32%) received monotherapy, and
      the rest were on combination therapy. In comparison, during the postpartum period
      only 14% of participants were not on any psychotropic medication, approximately
      35% received monotherapy, and over 50% were on combination therapy. While only
      13.5% of participants were on 3 or more psychotropic drugs during pregnancy,
      21.6% required 3 or more psychotropic drugs after childbirth in order to manage
      their symptoms. During pregnancy, 51 % of women had a mood episode compared to a
      recurrence rate of 70% in the postpartum period. LIMITATIONS: Small sample size,
      lack of a control group, and absence of random treatment assignment. CONCLUSIONS:
      The findings of this prospective, observational study indicate that the
      recurrence risk is much higher after childbirth than during pregnancy in spite of
      higher utilization of psychotropic drugs in the postpartum period.

PMID- 23859429
TI  - New diagnostic criteria for common variable immune deficiency (CVID), which may
      assist with decisions to treat with intravenous or subcutaneous immunoglobulin.
AB  - Common variable immune deficiency (CVID) is the most frequent symptomatic primary
      immune deficiency in adults. The standard of care is intravenous immunoglobulin
      (IVIG) or subcutaneous immunoglobulin (scIG) therapy. The cause of CVID is
      currently unknown, and there is no universally accepted definition of CVID. This
      creates problems in determining which patients will benefit from IVIG/scIG
      treatment. In this paper, we review the difficulties with the commonly used
      European Society of Immune Deficiencies (ESID) and the Pan American Group for
      Immune Deficiency (PAGID) definition of CVID. We propose new criteria for the
      diagnosis of CVID, which are based on recent scientific discoveries. Improved
      diagnostic precision will assist with treatment decisions including IVIG/scIG
      replacement. We suggest that asymptomatic patients with mild
      hypogammaglobulinaemia are termed hypogammaglobulinaemia of uncertain
      significance (HGUS). These patients require long-term follow-up, as some will
      evolve into CVID. 

PMID- 23859431
TI  - Safety of inhaled fluticasone propionate therapy for pediatric asthma - a
      systematic review.
AB  - CONTEXT AND AIM: Asthma is a common problem in paediatric population.
      International treatment guidelines recognize the role of inhaled corticosteroids
      for asthma in young children. Inhaled fluticasone propionate is reported to have
      greater systemic effects like other corticosteroids. Limited data is available on
      safety of this drug when used for longer duration. So, we conducted a systematic
      review to study the effect of inhaled fluticasone propionate on adrenal
      suppression, growth and bone mineral density in paediatric patients. DESIGN: A
      systematic review. METHODS: We searched for Randomized controlled trials in
      MEDLINE from January 2000 to December 2012. References of included study were
      hand searched. Information on study design, study population, drugs and dosage
      used, follow up period, measures used to evaluate safety and outcomes was
      abstracted independently by three reviewers. DETAILS OF INCLUDED STUDIES: In all
      included studies, participants were asthmatic children below 18 years and treated
      with fluticasone propionate. Minimum follow up considered was three months and
      should have measured HPA suppression or growth velocity or bone mineral density.
      RESULTS: Total ten studies were included. Studies which had monitored HPA
      function varied in dosage of drug, mode of administration and duration. Inspite
      of that it has been observed that serum cortisol level is affected by fluticasone
      propionate, no significant effect on bone mineral density was reported with
      fluticasone propionate, but the sample size was inadequate and dietary calcium
      intake was not recorded. None of the studies reported any significant reduction
      in growth when inhaled fluticasone propionate was used for the treatment of
      asthma, but the baseline growth and final adult height attained were not
      assessed. LIMITATION: This systematic review included only free full text
      articles published in English. Only randomized controlled trials were included.
      Cohort studies were not included. CONCLUSION: With available evidences, the
      safety of inhaled fluticasone propionate cannot be questioned. This systematic
      review could not derive any significant adverse effect on HPA function, growth
      and bone mineral density in asthmatic children when used for long duration and
      followed for up to three months.

PMID- 23859432
TI  - Electromagnetic field-induced converse cell growth during a long-term
      observation.
AB  - PURPOSE: Professional and public concern about the potential adverse effects of
      man-made electromagnetic fields (EMF) on the human body has dramatically expanded
      in recent years. Despite numerous attempts to investigate this issue, the long
      standing challenge of reproducibility surrounding alternating EMF effects on
      human health remains unresolved. Our chief aim was to investigate a plausible
      mechanism for this phenomenon. MATERIALS AND METHODS: Growth of cultured human
      cancer cells, DU145 and Jurkat, exposed to power frequency magnetic field (MF)
      (60 Hz, 1 mT) for 3 days, was determined using a 2-(4-Iodophenyl)- 3-(4
      nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) assay and a trypan blue
      exclusion assay. This experiment was repeated at incubators long-term monitoring
      period up to 5.3 years. A periodogram analysis was performed to investigate
      periodic patterns in the MF and sham effects on cell growth. RESULTS: Unlike
      conventional assumptions, the MF effect on growth in both cell types was
      promotive or suppressive in a period-dependent manner. The converse cell growth
      induced by the MF was consistent in incubators, with little variation.
      CONCLUSIONS: Spatiotemporal evidence suggests that the period-dependent converse
      cell growth by the MF may contribute to the poor reproducibility and explain the
      adverse effects observed in previous experimental and epidemiological
      investigations. Additionally, the novel approach of this study may be applied to
      design features required to experimentally determine the effects of EMF on living
      organisms in a convincing manner.

PMID- 23859433
TI  - The role of Bh4 in parallel evolution of hull colour in domesticated and weedy
      rice.
AB  - The two independent domestication events in the genus Oryza that led to African
      and Asian rice offer an extremely useful system for studying the genetic basis of
      parallel evolution. This system is also characterized by parallel de
      domestication events, with two genetically distinct weedy rice biotypes in the US
      derived from the Asian domesticate. One important trait that has been altered by
      rice domestication and de-domestication is hull colour. The wild progenitors of
      the two cultivated rice species have predominantly black-coloured hulls, as does
      one of the two U.S. weed biotypes; both cultivated species and one of the US
      weedy biotypes are characterized by straw-coloured hulls. Using Black hull 4
      (Bh4) as a hull colour candidate gene, we examined DNA sequence variation at this
      locus to study the parallel evolution of hull colour variation in the
      domesticated and weedy rice system. We find that independent Bh4-coding mutations
      have arisen in African and Asian rice that are correlated with the straw hull
      phenotype, suggesting that the same gene is responsible for parallel trait
      evolution. For the U.S. weeds, Bh4 haplotype sequences support current hypotheses
      on the phylogenetic relationship between the two biotypes and domesticated Asian
      rice; straw hull weeds are most similar to indica crops, and black hull weeds are
      most similar to aus crops. Tests for selection indicate that Asian crops and
      straw hull weeds deviate from neutrality at this gene, suggesting possible
      selection on Bh4 during both rice domestication and de-domestication. 

PMID- 23859434
TI  - Real-world rates, predictors, and associated costs of hypoglycemia among patients
      with type 2 diabetes mellitus treated with insulin glargine: results of a pooled
      analysis of six retrospective observational studies.
AB  - OBJECTIVE: To evaluate the real-world rates of hypoglycemia and related costs
      among patients with type 2 diabetes mellitus (T2DM) who initiated insulin
      glargine with either a disposable pen or vial-and-syringe. METHODS: Pooled data
      were evaluated from six previously published, retrospective, observational
      studies using US health plan insurance claims databases to investigate adults
      with T2DM who initiated insulin glargine. The current study evaluated baseline
      characteristics, hypoglycemic events, and costs during the 6 months prior to and
      12 months following insulin glargine initiation. Comparisons were made between
      patients initiating treatment with a disposable pen (GLA-P) and vial-and-syringe
      (GLA-V). Multivariate analyses using baseline characteristics as covariates
      determined predictors of hypoglycemia after initiating insulin glargine. RESULTS:
      This study included 23,098 patients (GLA-P: 14,911; GLA-V: 8187). Overall annual
      prevalence of hypoglycemia was low (6.3% overall, 2.2% related to hospital
      admission or emergency department visit). Prevalence was significantly lower with
      GLA-P (5.5% vs 7.7%; p < 0.0001). Furthermore, average glycated hemoglobin HbA1c
      reduction was higher with GLA-P (-1.22% vs -0.86%; p = 0.0012). The average
      annual hypoglycemia-related cost associated with initiating insulin glargine was
      $293, with GLA-P being 46% lower than GLA-V ($225 vs $417; p = 0.001). Patients
      who had already developed microvascular complications at the time of initiating
      insulin therapy were at higher risk for developing hypoglycemia. LIMITATIONS:
      This study is limited by the use of retrospective data and ICD-9-CM codes, which
      are subject to coding error. In addition, this pooled analysis used unmatched
      cohorts, with multivariate regression analyses employed to adjust for between
      group differences. Finally, results describe a managed care sample and cannot be
      generalized to all patients with T2DM. CONCLUSIONS: Patients with T2DM initiating
      insulin glargine treatment showed low rates of hypoglycemia, especially when
      using a disposable pen device. Hypoglycemia-related costs were low, contributing
      a very small proportion to overall diabetes-related healthcare costs.

PMID- 23859435
TI  - A prospective, multicenter, phase I matched-comparison group trial of safety,
      pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic
      spinal cord injury.
AB  - A prospective, multicenter phase I trial was undertaken by the North American
      Clinical Trials Network (NACTN) to investigate the pharmacokinetics and safety
      of, as well as obtain pilot data on, the effects of riluzole on neurological
      outcome in acute spinal cord injury (SCI). Thirty-six patients, with ASIA
      impairment grades A-C (28 cervical and 8 thoracic) were enrolled at 6 NACTN sites
      between April 2010 and June 2011. Patients received 50 mg of riluzole PO/NG twice
      daily, within 12 h of SCI, for 14 days. Peak and trough plasma concentrations
      were quantified on days 3 and 14. Peak plasma concentration (Cmax) and systemic
      exposure to riluzole varied significantly between patients. On the same dose
      basis, Cmax did not reach levels comparable to those in patients with amyotrophic
      lateral sclerosis. Riluzole plasma levels were significantly higher on day 3 than
      on day 14, resulting from a lower clearance and a smaller volume of distribution
      on day 3. Rates of medical complications, adverse events, and progression of
      neurological status were evaluated by comparison with matched patients in the
      NACTN SCI Registry. Medical complications in riluzole-treated patients occurred
      with incidences similar to those in patients in the comparison group. Mild-to
      moderate increase in liver enzyme and bilirubin levels were found in 14-70% of
      patients for different enzymes. Three patients had borderline severe elevations
      of enzymes. No patient had elevated bilirubin on day 14 of administration of
      riluzole. There were no serious adverse events related to riluzole and no deaths.
      The mean motor score of 24 cervical injury riluzole-treated patients gained 31.2
      points from admission to 90 days, compared to 15.7 points for 26 registry
      patients, a 15.5-point difference (p=0.021). Patients with cervical injuries
      treated with riluzole had more-robust conversions of impairment grades to higher
      grades than the comparison group.

PMID- 23859436
TI  - Different oligomeric properties and stability of highly homologous A1 and proto
      oncogenic A2 variants of mammalian translation elongation factor eEF1.
AB  - Translation elongation factor 1A (eEF1A) directs aminoacyl-tRNA to the A site of
      80S ribosomes. In addition, more than 97% homologous variants of eEF1A, A1 and
      A2, whose expression in different tissues is mutually exclusive, may fulfill a
      number of independent moonlighting functions in the cell; for instance, the
      unusual appearance of A2 in an A1-expressing tissue was recently linked to the
      induction of carcinogenesis. The structural background explaining the different
      functional performance of the highly homologous proteins is unclear. Here, the
      main difference in the structural properties of these proteins was revealed to be
      the improved ability of A1 to self-associate, as demonstrated by synchrotron
      small-angle X-ray scattering (SAXS) and analytical ultracentrifugation. Besides,
      the SAXS measurements at different urea concentrations revealed the low
      resistance of the A1 protein to urea. Titration of the proteins by hydrophobic
      dye 8-anilino-1-naphthalenesulfonate showed that the A1 isoform is more
      hydrophobic than A2. As the different association properties, lipophilicity, and
      stability of the highly similar eEF1A variants did not influence considerably
      their translation functions, at least in vitro, we suggest this difference may
      indicate a structural background for isoform-specific moonlighting roles. 

PMID- 23859437
TI  - Spontaneous transition of micelle-vesicle-micelle in a mixture of cationic
      surfactant and anionic surfactant-like ionic liquid: a pure nonlipid small
      unilamellar vesicular template used for solvent and rotational relaxation study.
AB  - The micelle-vesicle-micelle transition in aqueous mixtures of the cationic
      surfactant cetyl trimethyl ammonium bromide (CTAB) and the anionic surfactant
      like ionic liquid 1-butyl-3-methylimidazolium octyl sulfate, [C4mim][C8SO4] has
      been investigated by using dynamic light scattering (DLS), transmission electron
      microscopy (TEM), surface tension, conductivity, and fluorescence anisotropy at
      different volume fractions of surfactant. The surface tension value decreases
      sharply with increasing CTAB concentration up to ~0.38 volume fraction and again
      increases up to ~0.75 volume fraction of CTAB. Depending upon their relative
      amount, these surfactants either mixed together to form vesicles and/or micelles,
      or both of these structures were in equilibrium. Fluorescence anisotropy of 1,6
      diphenyl-1,3,5-hexatriene (DPH), incorporated in this system at different
      composition of surfactant indicates the formation of micelle and vesicle
      structures. The apparent hydrodynamic diameter of these large multilamellar
      vesicles is about ~200 nm-300 nm obtained by DLS measurement and finally
      confirmed by TEM micrographs. The large multilamellar vesicles are transformed
      into small unilamellar ones by sonication using a Lab-line instruments probe
      sonicator with a diameter of ~90-125 nm. To investigate the heterogeneity,
      solvent, and rotational relaxation of coumarin-153 (C-153) have been investigated
      in these unilamellar vesicles by using picosecond time-resolved fluorescence
      spectroscopic technique. The solvation dynamics of C-153 in these vesicles is
      found to be biexponential with average time constant ~580 ps. This indicates the
      slow relaxation of water molecules in the surfactant bilayer. In accordance with
      solvation dynamics, fluorescence anisotropy analysis of C-153 in unilamellar
      vesicles also indicates hindered rotation compared to bulk water. 

PMID- 23859439
TI  - Cooling by H3(+) emission.
AB  - Emission by the H3(+) molecular ion may be important in determining the energy
      balance in astrophysical situations, such as in (exo)planetary atmospheres. Here
      we report the calculation of a new cooling function, based on refitted partition
      functions and a recalculation of the total energy emitted by the molecule. This
      new function gives significantly increased cooling at higher temperatures,
      typical of those found in the atmospheres of gas giants. It is shown that
      nonthermal effects also need to be considered. A link to a web-based code to
      calculate radiative cooling in H2/H3(+) gas mixtures, including the effects of
      departures from equilibrium, is provided. 

PMID- 23859438
TI  - Patients as collaborators: using focus groups and feedback sessions to develop an
      interactive, web-based self-management intervention for chronic pain.
AB  - OBJECTIVES: To describe the development of an interactive, web-based self
      management intervention for opioid-treated, chronic pain patients with aberrant
      drug-related behavior. METHODS: Fifty-three chronic pain patients participated in
      either focus groups (N = 23) or individual feedback sessions (N = 30). Focus
      groups probed interest in and relevance of the planned content and structure of
      the program. Individual session participants reviewed draft program modules and
      provided feedback on acceptability, ease of use, and usefulness. Focus group
      transcripts were thematically analyzed, and summary statistics were performed on
      feedback data. RESULTS: Focus group participants stressed the need for additional
      pain management strategies and emphasized themes consistent with planned program
      content related to: 1) ambivalence about opioids; 2) reciprocal relationships
      among cognition, mood, and pain; 3) importance of recognizing physical
      limitations; and 4) effectiveness of goal setting for increasing motivation and
      functioning. Participants also offered insights on: 5) the loss of identity due
      to chronic pain; and 6) the desire to connect with pain peers to share strategies
      for managing daily life. Feedback session data demonstrate that participants
      believed that a web-based tool would be potentially useful and acceptable, and
      that exposure to program sections significantly increased participants' knowledge
      of key topics related to self-management of chronic pain. CONCLUSIONS: Results
      suggest the potential value of self-management for chronic pain patients and the
      potential acceptability of web-based delivery of intervention content. Focus
      group and feedback methodologies highlight the usefulness of including potential
      program users in intervention development.

PMID- 23859440
TI  - Evolution of a health navigator model of care within a primary care setting: a
      case study.
AB  - OBJECTIVE: Patient navigation originated as an approach for reducing disparities
      in cancer care and consequent health outcomes. Over time navigator models have
      evolved and been used to address various health issues in differing contexts.
      This case study outlines the evolution, purpose and effects of a lay-led health
      navigator model in a deprived, sparsely populated, New Zealand rural setting,
      where primary care services are frequently understaffed and routinely
      overstretched. METHODS: Routinely collected service utilisation data, survey
      results and health navigator interview data were utilised to illustrate the
      client group the service works with, why primary care refer to the service, as
      well as lessons learned from implementation to ongoing service provision.
      RESULTS: Those referred to the navigator service generally represented the most
      vulnerable in the community. Survey respondents, overall, were highly satisfied
      with the service. Navigators identified barriers and facilitators to
      implementation, as well as ongoing obstacles and enablers to service provision.
      CONCLUSIONS: This lay-led navigator service provided support to a group of unwell
      individuals, with few resources and multiple barriers to negotiate, and has
      effectively engaged with health and social care services, while overcoming
      various barriers and obstacles to its establishment and ongoing operation.

PMID- 23859441
TI  - Rapid detection of drugs of abuse in saliva using surface enhanced Raman
      spectroscopy and microfluidics.
AB  - We present a microfluidic device that detects trace concentrations of drugs of
      abuse in saliva within minutes using surface-enhanced Raman spectroscopy (SERS).
      Its operation is demonstrated using methamphetamine. The detection scheme
      exploits concentration gradients of chemicals, fostered by the laminar flow in
      the device, to control the interactions between the analyte, silver nanoparticles
      (Ag-NPs), and a salt. Also, since all species interact while advecting
      downstream, the relevant reaction coordinates occur with respect to the position
      in the channel. The system was designed to allow the analyte first to diffuse
      into the side stream containing the Ag-NPs, on which it is allowed to adsorb,
      before salt ions are introduced, causing the Ag-NPs to aggregate, and so creating
      species with strong SERS signal. The device allows partial separation via
      diffusion of the analyte from the complex mixture. Also, the reproducible salt
      induced NP aggregation decouples the aggregation reaction (necessary for strong
      SERS) from the analyte concentration or charge. This method enables the creation
      of a region where detection of the analyte of interest via SERS is optimal, and
      dramatically extends the classes of molecules and quality of signals that can be
      measured using SERS, compared to bulk solution methods. The spatial distribution
      of the SERS signals was used to map the degree of nanoparticle aggregation and
      species diffusion in the channel, which, together with numerical simulations, was
      used to describe the kinetics of the colloid aggregation reaction, and to
      determine the optimal location in the channel for SERS interrogation. 

PMID- 23859442
TI  - Modeling the concentrations of on-road air pollutants in southern California.
AB  - High concentrations of air pollutants on roadways, relative to ambient
      concentrations, contribute significantly to total personal exposure. Estimation
      of these exposures requires measurements or prediction of roadway concentrations.
      Our study develops, compares, and evaluates linear regression and nonlinear
      generalized additive models (GAMs) to estimate on-road concentrations of four key
      air pollutants, particle-bound polycyclic aromatic hydrocarbons (PB-PAH),
      particle number count (PNC), nitrogen oxides (NOx), and particulate matter with
      diameter <2.5 MUm (PM2.5) using traffic, meteorology, and elevation variables.
      Critical predictors included wind speed and direction for all the pollutants,
      traffic-related variables for PB-PAH, PNC, and NOx, and air temperatures and
      relative humidity for PM2.5. GAMs explained 50%, 55%, 46%, and 71% of the
      variance for log or square-root transformed concentrations of PB-PAH, PNC, NOx,
      and PM2.5, respectively, an improvement of 5% to over 15% over the linear models.
      Accounting for temporal autocorrelation in the GAMs further improved the
      prediction, explaining 57-89% of the variance. We concluded that traffic and
      meteorological data are good predictors in estimating on-road traffic-related air
      pollutant concentrations and GAMs perform better for nonlinear variables, such as
      meteorological parameters. 

PMID- 23859444
TI  - Hydrogen-bonding-facilitated layer-by-layer growth of ultrathin organic
      semiconducting films.
AB  - We demonstrated that the layer-by-layer growth of thin film crystals of
      conjugated organic molecules is facilitated by their hydrogen-bonding
      capabilities. We synthesized bis(3-hydroxypropyl)-sexithiophene (bHP6T), which
      includes two hydroxyalkyl groups that promote interlayer and intermolecular
      molecular interactions during the crystal growth process. Under the optimal
      deposition conditions, the crystals grew in a nearly perfect layer-by-layer mode
      on the solid substrate surfaces, enabling the formation of uniform charge
      transporting films as thin as a few monolayers. A thin film transistor device
      prepared from a bHP6T film only 9 nm thick exhibited a charge carrier mobility
      well above 1 * 10(-2) cm(2)/(V s) and an on/off ratio exceeding 1 * 10(4). These
      properties are better than the properties of other sexithiophene-based devices
      yet reported. The devices exhibited enhanced stability under atmospheric
      conditions, and they functioned properly, even after storage for more than 2
      months. 

PMID- 23859443
TI  - Molecular study of congenital erythrocytosis in 70 unrelated patients revealed a
      potential causal mutation in less than half of the cases (Where is/are the
      missing gene(s)?).
AB  - INTRODUCTION: Congenital erythrocytosis can be classified as primary, when the
      defect is intrinsic to the RBC progenitors and independent of the serum
      erythropoietin (Epo) concentration, or secondary, when the erythrocytosis is the
      result of an upregulation of Epo production. Primary erythrocytosis is associated
      with mutations in the EPOR gene, secondary CE can de due to mutations that
      stabilize the hemoglobin in the oxygenated form or to mutations in the genes that
      control the transcriptional activation of the EPO gene - VHL, EGLN1, EPAS1.
      Chuvash polycythemia, caused by mutations in VHL gene, shares features of both
      primary and secondary erythrocytosis, with increased Epo production but also
      hypersensitivity of progenitors to Epo. MATERIAL AND METHODS: With the main
      objective of describing the etiology and molecular basis of CE, we have studied
      70 consecutive unrelated patients presenting with idiopathic erythrocytosis from
      our hematology clinic or referred from other centers. According to a study
      algorithm, we have sequenced all the genes described as associated with CE.
      RESULTS AND DISCUSSION: Erythrocytosis molecular etiology was identify in 25
      (36%) of the 70 subjects. High-affinity Hb variants were the most common cause,
      present in 20% of the cases. New mutations were identified in the JAK2, EPOR,
      VHL, and EGLN1 genes. CONCLUSIONS: High-affinity hemoglobin variants are a very
      rare cause of secondary CE, but it seems likely that their incidence may be
      underestimated. Our experience shows that in erythrocytosis with a dominant
      inheritance and normal or inappropriate high Epo levels, the HBB and HBA genes
      should be the first to be studied. In spite of the seven genes known to be
      involved in CE, the majority of the cases have unknown etiology.

PMID- 23859445
TI  - Dermatitis herpetiformis - what lies beneath the skin?

PMID- 23859446
TI  - Does dermatitis herpetiformis result in bone loss as coeliac disease does? A
      cross sectional study.
AB  - INTRODUCTION AND OBJECTIVES: coeliac disease (CD) and its cutaneous
      manifestation, dermatitis herpetiformis are both (DH) gluten-sensitive diseases.
      Metabolic bone disease is common among patients with CD, even in asymptomatic
      forms. Data are scarce about bone density in patients with dermatitis
      herpetiformis. The aim of our study was to compare bone mineral density (BMD) of
      celiac and dermatitis herpetiformis patients. METHODS: 34 coeliac patients, 53
      with dermatitis herpetiformis and 42 healthy controls were studied. The mean age
      was 38.0 +/- 12.1, 32.18 +/- 14.95, 35.33 +/- 10.41 years in CD, dermatitis
      herpetiformis, and healthy controls, respectively. Bone mineral density of the
      lumbar spine, the left femoral neck and radius were measured by dual-energy X-ray
      absorptiometry. Low bone density, osteopenia and osteoporosis were defined as a
      body mass density (BMD) T-score between 0 and -1, between -1 and -2.5, and under 
      2.5, respectively. RESULTS: at lumbar region, consisting of dominantly trabecular
      compartment, a decreased BMD was detected in 49 % (n = 26) patients with
      dermatitis herpetiformis, 62 % (n = 21) of CD patients, and 29 % (n = 12) of
      healthy controls, respectively. Lower BMD were measured at the lumbar region in
      dermatitis herpetiformis and CD compared to healthy subjects (0.993 +/- 0.136
      g/cm2 and 0.880 +/- 0.155 g/cm2 vs. 1.056 +/- 0.126 g/cm2; p < 0.01). Density of
      bones consisting of dominantly cortical compartment (femoral neck) did not differ
      in dermatitis herpetiformis and healthy subjects. CONCLUSIONS: our results show
      that a low bone mass is also frequent among patients with dermatitis
      herpetiformis. Bone mineral content in these patients is significantly lower in
      those parts of the skeleton which contain more trabecular than cortical bone.

PMID- 23859447
TI  - The influence of advanced age on the morbi-mortality of gastric cancer after
      curative surgery.
AB  - INTRODUCTION: gastric cancer (GC) is the fourth leading cause of cancer death in
      Spain after lung, colorectal, breast and prostate tumours. Surgery remains the
      only potentially curative treatment in localized gastric cancer. OBJECTIVE: the
      aim of our study is to evaluate and compare the clinical and surgical aspects,
      development of postoperative complications and outcomes of patients over 75 years
      old compared with younger patients in our centre. MATERIAL AND METHODS:
      comparative retrospective study, from March 2003 to June 2011. We diagnosed 166
      cases of GC, 109 (65 %) underwent curative surgery. Two groups were settled:
      group M: < or = 75 years (41 patients) and group m: < 75 years (68 patients). We
      analyzed age, sex, comorbidities, tumour location, clinical stage, perioperative
      chemotherapy, surgical technique, postoperative complications, recurrence and
      mortality from cancer. RESULTS: a more frequent presence of cardiovascular
      comorbidities and a greater postoperative mortality by medical causes were the
      only significant differences between both groups. Also, a lower proportion of
      patients in group M received preoperative chemotherapy and underwent D1
      lymphadenectomy. However, the rate of local and systemic recurrence and overall
      survival were similar in both groups. CONCLUSIONS: age should not be considered a
      contraindication for curative surgery on GC. The general condition and
      comorbidities are more important to contraindicate surgical treatment.

PMID- 23859448
TI  - Histamine intolerance as a cause of chronic digestive complaints in pediatric
      patients.
AB  - INTRODUCTION: histamine intolerance (HI) is a poorly described disease in
      gastroenterology that may present with predominant digestive complaints. The
      goals of this study include a report of two cases diagnosed in a pediatric
      gastroenterology clinic. MATERIAL AND METHODS: observational, retrospective study
      of patients diagnosed with HI from September 2010 to December 2011 at the
      pediatric gastroenterology clinic of a tertiary hospital.They were deemed to have
      a diagnosis of HI in the presence of 2 or more characteristic digestive
      complaints, decreased diamino oxidase (DAO) levels and/or response to a low
      histamine diet with negative IgE-mediated food allergy tests. RESULTS: sixteen
      patients were diagnosed. Males predominated versus females (11/5). Mean age at
      symptom onset was 4 years (6 months vs. 13 years and 6 months) and mean age at
      diagnosis was 6 years and 6 months (17 months vs. 13 years and 11 months), with
      an interval of 2 years and 1 month between symptom onset and diagnosis (5 months
      vs. 4 years). Predominant symptoms included diffuse abdominal pain (16/16),
      intermittent diarrhea (10/16), headache (5/16), intermittent vomiting (4/16), and
      skin rash (2/16). The diagnosis was established by measuring plasma diamino
      oxidase levels, which were below 10 kU/L (normal > 10 kU/L) in 14 cases, and
      symptom clearance on initiating a low histamine diet. In two patients DAO levels
      were above 10 kU/L but responded to diet. Treatment was based on a diet low in
      histamine-contaning food, and antihistamines H1 y H2 had to be added for two
      cases. CONCLUSIONS: histamine intolerance is a little known disease with a
      potentially relevant incidence. Predominant complaints include diffuse abdominal
      pain, diarrhea, headache, and chronic intermittent vomiting. Its diagnosis is
      based on clinical suspicion, plasma DAO measurement, and response to a low
      histamine diet. Management with the latter provides immediate improvement.

PMID- 23859449
TI  - Comparative study of a responsive insertion technology (RIT) colonoscope versus a
      variable-stiffness colonoscope.
AB  - BACKGROUND AND OBJECTIVES: recently, Olympus developed a new prototype (XCF
      Q180AY2L) with responsive insertion technology (RIT), which besides the still
      known variable stiffness technology, included a passive bending section and a new
      high force insertion tube. Our objective was to investigate whether the use of
      this prototype could ease colonoscope insertion, increasing the cecal intubation
      rate, and/or shortening the cecal intubation time. MATERIAL AND METHODS: the
      study was designed as a prospective observational study in 305 consecutive
      patients from a colo-rectal cancer screening program. We compared colonoscopies
      performed with conventional colonoscopes (CFH180AL/CFQ160L) with those performed
      with the prototype XCF-Q180AY2L. End points were mean cecal and terminal ileal
      intubation times, cecum intubation rate, and need for specific maneuvers. All
      colonoscopies were performedunder sedation with intravenous propofol. Finally,
      288 patients were included. RESULTS: no complications were observed. Complete
      cecal intubation rate was 100 % in both groups. The ileum could be reached in
      98.95 % of cases. Mean time required to reach the cecum was shorter in the
      prototype endoscope group (4.31 min, SD 2.63 min) than in the conventional
      endoscope group (4.66 min, SD 2.52 min) (p < 0.05). Compared with the standard
      colonoscope group, we observed in the prototype group less subjective sensation
      of difficultyin the passage of the sigma (p < 0.01), fewer maneuvers when it
      proved necessary to straighten the scope (p < 0.01), and less frequent need to
      modify the stiffness of the endoscope (p < 0.05). CONCLUSION: we concluded that
      the prototype endoscope (XCFQ180AY2L) facilitated colonoscope insertion,
      requiring slightly less time to reach the cecum than a standard colonoscope.

PMID- 23859450
TI  - The role of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) in non
      small cell lung cancer (NSCLC) patients: SEED-SEPD-AEG Joint Guideline.
AB  - Lung cancer is one of the most frequent neoplasms in our environment, and
      represents the first cause of cancer related death in western countries.
      Diagnostic and therapeutic approach to these patients may be complicated, with
      endoscopic ultrasound guided fine needle aspiration (EUS-FNA), classically
      performed by gastroenterologists, playing a very important role. As this disease
      is not closely related to the "digestive tract", gastroenterologists have been
      forced to update their knowledge on this field o adequately diagnose this
      significant group of patients. The recent advent of modern and promising
      techniques like endobronchial ultrasound guided fine needle aspiration (EBUS-FNA)
      have prompted new approaches for diagnosis and staging of this type of patients.
      In this clinical guideline, the "Sociedad Espanola de Endoscopia Digestiva"
      (SEED), "Sociedad Espanola de Patologia Digestiva" (SEPD) and the
      "AsociacionEspanola de Gastroenterologia", have jointed efforts to update the
      existing knowledge on the field and provide their members with evidence based
      recommendations. 

PMID- 23859451
TI  - Loop type cecal volvulus: Multidetector computed tomography (MDCT) findings.

PMID- 23859452
TI  - Morgagni's hernia containing an appendicular mucocele.

PMID- 23859453
TI  - Adult hepatoblastoma.
AB  - Adult hepatoblastoma (AHB) is a very rare tumor, having been described 45 cases
      up to June 2012. In contrast to HB in infancy (IHB), it has poor prognosis. We
      present the case of a 37-year-old asymptomatic woman who consulted for a large 
      12 cm diameter- mass involving segments 5 and 6 of the liver, and alfa
      fetoprotein of 1,556,30 UI/mL. A bisegmentectomy was carried out. The microscopic
      study confirmed the AHB diagnosis, revealing the presence of epithelial cells
      forming clusters, trabecular patterns and tubules. The patient died on the 10th
      postoperative month due to progression disease.The Wnt/Beta-Catenin signaling
      pathway mutation has been reported and associated with a poor prognosis in IHB.
      Due to the AHB poor prognosis, seems reasonable to introduce the therapeutic
      regimens described in children who have a better outcome. 

PMID- 23859454
TI  - Colonic necrosis due to calcium polystyrene sulfonate (Kalimate) not suspended in
      sorbitol.
AB  - Cation-exchange resins are used in the management of hyperkalemia, particularly
      in patients with end-stage renal disease. These resins were associated with
      gastrointestinal tract lesions, especially sodium polystyrene sulfonate
      (Kayexalate) mixed with sorbitol. We present a case of colonic necrosis after the
      administration of calcium polystyrene sulfonate (Kalimate) not suspended in
      sorbitol. 

PMID- 23859455
TI  - [Elastography of the liver (Fibroscan(r)) in hepatology].

PMID- 23859456
TI  - Superior mesenteric artery syndrome: diagnostic and therapeutic considerations.

PMID- 23859457
TI  - Spontaneous omental bursa hemorrhage as the main presentation of a
      gastrointestinal stromal tumor: a case report.

PMID- 23859458
TI  - Hemangioendothelioma and other small bowel tumors as a cause of obscure
      gastrointestinal bleeding.

PMID- 23859459
TI  - Inflammatory cloacogenic polyp: a rare cause of lower gastrointestinal bleeding.

PMID- 23859460
TI  - Value of laparoscopy in the treatment of cecal perforation by a foreign body;
      differential diagnosis of appendicitis.

PMID- 23859461
TI  - Superoxide-dependent uptake of vitamin C in human glioma cells.
AB  - Glioblastomas are lethal brain tumors that resist current cytostatic therapies.
      Vitamin C may antagonize the effects of reactive oxygen species (ROS) generating
      therapies; however, it is often used to reduce therapy-related side effects
      despite its effects on therapy or tumor growth. Because the mechanisms of vitamin
      C uptake in gliomas are currently unknown, we evaluated the expression of the
      sodium-vitamin C cotransporter (SVCT) and facilitative hexose transporter (GLUT)
      families in human glioma cells. In addition, as microglial cells can greatly
      infiltrate high-grade gliomas (constituting up to 45% of cells in glioblastomas),
      the effect of TC620 glioma cell interactions with microglial-like HL60 cells on
      vitamin C uptake (Bystander effect) was determined. Although glioma cells
      expressed high levels of the SVCT isoform-2 (SVCT2), low functional activity,
      intracellular localization and the expression of the dominant-negative isoform
      (dnSVCT2) were observed. The increased glucose metabolic activity of glioma cells
      was evident by the high 2-Deoxy-d-glucose and dehydroascorbic acid (DHA) uptake
      rates through the GLUT isoform-1 (GLUT1), the main DHA transporter in
      glioblastoma. Co-culture of glioma cells and activated microglial-like HL60 cells
      resulted in extracellular ascorbic acid oxidation and high DHA uptake by glioma
      cells. This Bystander effect may explain the high antioxidative potential
      observed in high-grade gliomas. This study strongly suggests that the Bystander
      effect, that is, glioma cell interaction with oxidant-producing microglia, could
      be an important mechanism for glioma vitamin C loading in the absence of
      functional sodium-vitamin C cotransporter 2 (SVCT2) expression. The high cellular
      vitamin C load in glioma cells results from a high uptake of extracellular
      dehydroascorbic acid (DHA) generated by neighboring microglia. This Bystander
      effect may explain the high antioxidative potential observed in high-grade
      gliomas, considering that high-grade gliomas may be the only neoplasm where
      oxidant-producing microglia can almost equal the number of tumor cells. 

PMID- 23859462
TI  - Design, synthesis, and antitumor activity of novel podophyllotoxin derivatives as
      potent anticancer agents.
AB  - In order to find novel synthetic compounds with superior antitumor activity and
      overcome multidrug resistance, a series of novel 4beta-N-substituted
      podophyllotoxin derivatives were synthesized under mild conditions with
      satisfactory yield. Nine novel podophyllotoxin derivatives were synthesized by
      linking 4beta-amino-podophyllotoxin with aldehydes via the formation of a
      Schiff's base, and imines were reducted to secondary amines. These novel
      derivatives have been evaluated for cytotoxicity against human cancer cell lines
      Hela, K562, and K562/AO2. The results indicated that these compounds possess
      superior bioactivity (IC50 values were found at the range of 10(- 6)-10(- 8)
      mol/l) and weak multidrug resistance. 

PMID- 23859464
TI  - Anatomical differences in the human inferior colliculus relate to the perceived
      valence of musical consonance and dissonance.
AB  - Helmholtz himself speculated about a role of the cochlea in the perception of
      musical dissonance. Here we indirectly investigated this issue, assessing the
      valence judgment of musical stimuli with variable consonance/dissonance and
      presented diotically (exactly the same dissonant signal was presented to both
      ears) or dichotically (a consonant signal was presented to each ear--both
      consonant signals were rhythmically identical but differed by a semitone in
      pitch). Differences in brain organisation underlying inter-subject differences in
      the percept of dichotically presented dissonance were determined with voxel-based
      morphometry. Behavioral results showed that diotic dissonant stimuli were
      perceived as more unpleasant than dichotically presented dissonance, indicating
      that interactions within the cochlea modulated the valence percept during
      dissonance. However, the behavioral data also suggested that the dissonance
      percept did not depend crucially on the cochlea, but also occurred as a result of
      binaural integration when listening to dichotic dissonance. These results also
      showed substantial between-participant variations in the valence response to
      dichotic dissonance. These differences were in a voxel-based morphometry analysis
      related to differences in gray matter density in the inferior colliculus, which
      strongly substantiated a key role of the inferior colliculus in
      consonance/dissonance representation in humans.

PMID- 23859463
TI  - A novel long-acting glucose-dependent insulinotropic peptide analogue: enhanced
      efficacy in normal and diabetic rodents.
AB  - AIM: Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone that
      is released from intestinal K cells in response to nutrient ingestion. We aimed
      to investigate the therapeutic potential of the novel N- and C-terminally
      modified GIP analogue AC163794. METHODS: AC163794 was synthesized by solid-phase
      peptide synthesis. Design involved the substitution of the C-terminus tail region
      of the dipeptidyl peptidase IV (DPP-IV)-resistant GIP analogue [d-Ala(2) ]GIP(1
      42) with the unique nine amino acid tail region of exenatide. The functional
      activity and binding of AC163794 to the GIP receptor were evaluated in RIN-m5F
      beta-cells. In vitro metabolic stability was tested in human plasma and kidney
      membrane preparations. Acute insulinotropic effects were investigated in isolated
      mouse islets and during an intravenous glucose tolerance test in normal and
      diabetic Zucker fatty diabetic (ZDF) rats. The biological actions of AC163794
      were comprehensively assessed in normal, ob/ob and high-fat-fed streptozotocin
      (STZ)-induced diabetic mice. Acute glucoregulatory effects of AC163794 were
      tested in diet-induced obese mice treated subchronically with AC3174, the
      exendatide analogue [Leu(14) ] exenatide. Human GIP or [d-Ala(2) ]GIP(1-42) were
      used for comparison. RESULTS: AC163794 exhibited nanomolar functional GIP
      receptor potency in vitro similar to GIP and [d-Ala(2) ]GIP(1-42). AC163794 was
      metabolically more stable in vitro and displayed longer duration of
      insulinotropic action in vivo versus GIP and [d-Ala(2) ]GIP(1-42). In diabetic
      mice, AC163794 improved HbA1c through enhanced insulinotropic action, partial
      restoration of pancreatic insulin content and improved insulin sensitivity with
      no adverse effects on fat storage and metabolism. AC163794 provided additional
      baseline glucose-lowering when injected to mice treated with AC3174. CONCLUSIONS:
      These studies support the potential use of a novel GIP analogue AC163794 for the
      treatment of type 2 diabetes.

PMID- 23859465
TI  - Optimal scanning of all single-point mutants of a protein.
AB  - In protein engineering, useful information may be gained from systematically
      generating and screening all single-point mutants of a given protein. We model
      and analyze an iterative two-stage procedure to generate all these mutants. At
      each position, L variants are generated in the first stage via saturation
      mutagenesis and are sequenced. In the second stage, the missing variants (out of
      the 19 possible single-point substitutions) are produced via site-directed
      mutagenesis. We study the economic tradeoff associated with varying L, and derive
      its optimal value given the experimental parameters.

PMID- 23859466
TI  - Differences in carbon density and soil CH4/N2O flux among remnant and agro
      ecosystems established since European settlement in the Mornington Peninsula,
      Australia.
AB  - National and regional C emissions from historical land use change (LUC) and
      fossil fuel use are proposed as a basis to ascribe 'burden-sharing' for global
      emission reduction targets. Changes in non-CO2 greenhouse gas emissions as a
      result of LUC have not been considered, but may be considerable. We measured soil
      atmosphere exchange of methane (CH4) and nitrous oxide (N2O) in remnant forest,
      pasture and viticulture systems in four seasons, as well as differences in soil C
      density and the C density of remnant forest vegetation. This approach enabled
      comparative assessment of likely changes in ecosystem C density and soil non-CO2
      greenhouse gas exchange along a LUC continuum since European settlement. Soil CH4
      uptake was moderate in forest soil (-27 MUg C m(-2) h(-1)), and significantly
      different to occasionally large CH4 emissions from viticulture and pasture soils.
      Soil N2O emissions were small and did not significantly differ. Soil C density
      increased significantly with conversion from forest (5 kg m(-2)) to pasture (9 kg
      m(-2)), and remained high in viticulture. However, there was a net decrease in
      ecosystem C density with forest conversion to pasture. Concurrently, net soil non
      CO2 emissions (CH4 and N2O combined) increased with conversion from forest to
      pasture. Since European settlement 170 years ago, it was estimated ~8114 Gg CO2-e
      has been released from changes in ecosystem C density in the Mornington
      Peninsula, whereas ~383 Gg CO2-e may have been released from changes in soil non
      CO2 exchange processes. Principally, a switch from soil CH4 uptake to soil CH4
      emission after forest clearing to agro-pastoral systems provided this further ~5%
      contribution to the historical landscape CO2-e source strength. Conserving and
      restoring remnant forests and establishing new tree-based systems will enhance
      landscape C density. Similarly, minimising anaerobic, wet conditions in
      pasture/viticulture soils will help reduce non-CO2 greenhouse gas emissions.

PMID- 23859467
TI  - Injury thresholds of knee ligaments under lateral-medial shear loading: an
      experimental study.
AB  - OBJECTIVE: Knee ligament injuries frequently cause devastating impairment to the
      injured. In car-pedestrian impact accidents, lateral-medial shear displacement is
      one of principal mechanisms of knee ligament injuries. The current study aims to
      investigate injury thresholds of knee ligaments under lateral-medial shear
      loading to improve pedestrian safety. METHODS: Ten isolated human knee joints
      without surrounding muscles were tested under dynamic lateral-medial shear
      loading in 2 groups: 3 left knee joints were tested in the shearing of medial
      tibial translation, and other knee joints were tested in lateral tibial
      translation. Based on combined analysis of experimental videos and force curves,
      the primary failure time of knee ligaments and the corresponding shear
      displacement were determined. RESULTS: Under lateral tibial translation and
      medial tibial translation, both primary injury types of knee ligaments and force
      curves showed essential differences. It appears that the majority of primary
      failure modes were anterior cruciate ligament (ACL) injury when the tibia was
      displaced medially and posterior cruciate ligament (PCL) injury when the tibia
      was displaced laterally. Overall experimental results indicated that the injury
      threshold of the knee joint under lateral-medial shear loading varied from 11.4
      to 17.6 mm, with an average level approximately 14.3 mm. CONCLUSION: Based on the
      bone-ligament-bone complex experiment of the knee, we present injury occurrences
      of the knee joints in lateral and medial shear loading. The testing data provide
      a basis for improving knee injury criteria that regulate passenger cars to reduce
      their aggressiveness to pedestrians.

PMID- 23859468
TI  - Identification of large selective sweeps associated with major genes in cattle.
AB  - Selection for new favorable variants can lead to selective sweeps. However, such
      sweeps might be rare in the evolution of different species for which polygenic
      adaptation or selection on standing variation might be more common. Still, strong
      selective sweeps have been described in domestic species such as chicken lines or
      dog breeds. The goal of our study was to use a panel of individuals from 12
      different cattle breeds genotyped at high density (800K SNPs) to perform a whole
      genome scan for selective sweeps defined as unexpectedly long stretches of
      reduced heterozygosity. To that end, we developed a hidden Markov model in which
      one of the hidden states corresponds to regions of reduced heterozygosity. Some
      unexpectedly long regions were identified. Among those, six contained genes known
      to affect traits with simple genetic architecture such as coat color or horn
      development. However, there was little evidence for sweeps associated with genes
      underlying production traits. 

PMID- 23859469
TI  - Health care provider recommendations for reducing cancer risks among women with a
      BRCA1 or BRCA2 mutation.
AB  - There is a significant variation in the uptake of cancer risk reducing options by
      women with a BRCA1 or BRCA2 mutation. It is currently unclear why these
      differences exist and it is possible that recommendations vary between providers
      and these influence patient decisions. Eligible health care providers who provide
      genetic counseling for hereditary breast and ovarian cancer families in Canada
      were identified. Each provider was asked to complete a study specific
      questionnaire that included their opinion of various cancer risk reduction
      options and their recommendations for specific cases. Respondents recommended
      prophylactic oophorectomy more often than prophylactic mastectomy or tamoxifen
      for women with a BRCA1 or BRCA2 mutation (p < 0.0001). Fewer than half of the
      respondents agreed with the recommendation for prophylactic mastectomy, and a
      minority of the respondents supported the recommendation for tamoxifen for
      chemoprevention. The majority of Canadian genetics health care providers adhere
      to the National Comprehensive Cancer Network (NCCN) Guideline of recommending
      prophylactic oophorectomy to mutation carriers, however, the minority of genetics
      health care providers recommend either prophylactic mastectomy or tamoxifen. 

PMID- 23859470
TI  - Genome damage in testicular seminoma patients seven years after radiotherapy.
AB  - PURPOSE: Testicular seminoma cancer incidence has significantly increased over
      the last few decades, and although it is successfully treated by radiotherapy,
      long-term health risks are still unclear. The aim of the study was to show long
      term genome damage in patients with seminoma after radiotherapy. MATERIALS AND
      METHODS: Chromosome aberration (CA) and micronucleus (MN) assays seven years
      after radiotherapy with a total dose of 25 Gy were conducted in 10 testicular
      seminoma patients aged 23-49 years and results were compared with 10 healthy
      control subjects matched for age and smoking status. RESULTS: Although mean CA
      frequency did not deviate from control values, significantly increased
      frequencies of dicentrics, double minutes, and ring chromosomes were detected in
      seminoma patients. MN frequency in binuclear lymphocytes of patients was similar
      to controls (4.60/1000 vs. 5.82/1000, respectively). Significantly higher MN
      frequency was detected in mononuclear lymphocytes of patients than in controls
      (2.55/1000 vs. 0.73/1000, respectively). Average percentage of centromere
      positive MN was 62.6% in seminoma patients. CONCLUSION: This study shows the
      persistence of unstable CA in seminoma patients seven years after radiotherapy
      and the relevance of long-term follow up. MN frequency in mononuclear lymphocytes
      was shown to be relevant biomarker of long-term genome damage.

PMID- 23859471
TI  - Divergent sexual selection via male competition: ecology is key.
AB  - Sexual selection and ecological differences are important drivers of speciation.
      Much research has focused on female choice, yet the role of male competition in
      ecological speciation has been understudied. Here, we test how mating habitats
      impact sexual selection and speciation through male competition. Using limnetic
      and benthic species of threespine stickleback fish, we find that different mating
      habitats select differently on male traits through male competition. In mixed
      habitat with both vegetated and open areas, selection favours two trait
      combinations of male body size and nuptial colour: large with little colour and
      small with lots of colour. This matches what we see in reproductively isolated
      stickleback species, suggesting male competition could promote trait divergence
      and reproductive isolation. In contrast, when only open habitat exists, selection
      favours one trait combination, large with lots of colour, which would hinder
      trait divergence and reproductive isolation. Other behavioural mechanisms in male
      competition that might promote divergence, such as avoiding aggression with
      heterospecifics, are insufficient to maintain separate species. This work
      highlights the importance of mating habitats in male competition for both sexual
      selection and speciation. 

PMID- 23859472
TI  - A review of the possible mechanisms of action of tocotrienol - a potential
      antiosteoporotic agent.
AB  - Osteoporosis is posing a tremendous healthcare problem globally. Much effort has
      been invested in finding novel antiosteoporotic agents to stop the progression of
      this disease. Tocotrienol, one of the isoforms of vitamin E, is poised as a
      potential antiosteoporotic agent. Previous studies showed that tocotrienol as a
      single isomer or as a mixture demonstrated both anabolic and antiresorptive
      effects in various rodent models of osteoporosis. In vitro experiments further
      demonstrated that tocotrienol could up-regulate genes related to
      osteoblastogenesis and modify receptor activator of nuclear factor kappa B
      signaling against osteoclastogenesis. Additionally, tocotrienol was also shown to
      be a strong 3- hydroxy-3-methyl-glutaryl-CoA reductase down-regulator with a
      mechanism different from that of statins. Inhibition of the mevalonate pathway
      affects both osteoblast and osteoclast formation in favor of the former.
      Tocopherol, a more commonly used isoform of vitamin E does not possess similar
      effects. Tocotrienol is also a potent antioxidant. It can scavenge free radicals
      and prevent oxidative damage on osteoblast thus promoting its survival. It may
      also up-regulate the antioxidant defense network in osteoclast and indirectly act
      against free radical signaling essential in osteoclastogenesis. The effects of
      tocotrienol on Wnt/beta-catenin signaling essential in osteoblastogenesis have
      not been determined. More mechanistic studies need to be conducted to illustrate
      the antiosteoporotic effects of tocotrienol. Clinical trials are also required to
      confirm its effects in humans. In conclusion, tocotrienol demonstrates great
      potential as an antiosteoporotic agent and much research effort should be
      invested to develop it as an agent to curb osteoporosis. 

PMID- 23859473
TI  - Discordant genetic diversity and geographic patterns between Crassicutis
      cichlasomae (Digenea: Apocreadiidae) and its cichlid host, "Cichlasoma"
      urophthalmus (Osteichthyes: Cichlidae), in Middle-America.
AB  - Genetic analyses of hosts and their parasites are key to understand the
      evolutionary patterns and processes that have shaped host-parasite associations.
      We evaluated the genetic structure of the digenean Crassicutis cichlasomae and
      its most common host, the Mayan cichlid "Cichlasoma" urophthalmus, encompassing
      most of their geographical range in Middle-America (river basins in southeastern
      Mexico, Belize, and Guatemala together with the Yucatan Peninsula). Genetic
      diversity and structure analyses were done based on 167 cytochrome c oxidase
      subunit 1 sequences (330 bp) for C. cichlasomae from 21 populations and 161
      cytochrome b sequences (599 bp) for "C." urophthalmus from 26 populations.
      Analyses performed included phylogenetic tree estimation under Bayesian inference
      and maximum likelihood analysis, genetic diversity, distance and structure
      estimates, haplotype networks, and demographic evaluations. Crassicutis
      cichlasomae showed high genetic diversity values and genetic structuring,
      corresponding with 4 groups clearly differentiated and highly divergent.
      Conversely, "C." urophthalmus showed low levels of genetic diversity and genetic
      differentiation, defined as 2 groups with low divergence and with no
      correspondence with geographical distribution. Our results show that species of
      cichlids parasitized by C. cichlasomae other than "C." urophthalmus, along with
      multiple colonization events and subsequent isolation in different basins, are
      likely factors that shaped the genetic structure of the parasite. Meanwhile,
      historical long-distance dispersal and drought periods during the Holocene, with
      significant population size reductions and fragmentations, are factors that could
      have shaped the genetic structure of the Mayan cichlid.

PMID- 23859474
TI  - The C2 domains of otoferlin, dysferlin, and myoferlin alter the packing of lipid
      bilayers.
AB  - Ferlins are large multi-C2 domain membrane proteins involved in membrane fusion
      and fission events. In this study, we investigate the effects of binding of the
      C2 domains of otoferlin, dysferlin, and myoferlin on the structure of lipid
      bilayers. Fluorescence measurements indicate that multi-C2 domain constructs of
      myoferlin, dysferlin, and otoferlin change the lipid packing of both small
      unilamellar vesicles and giant plasma membrane vesicles. The activities of these
      proteins were enhanced in the presence of calcium and required negatively charged
      lipids like phosphatidylserine or phosphatidylglycerol for activity. Experiments
      with individual domains uncovered functional differences between the C2A domain
      of otoferlin and those of dysferlin and myoferlin, and truncation studies suggest
      that the effects of each subsequent C2 domain on lipid ordering appear to be
      additive. Finally, we demonstrate that the activities of these proteins on
      membranes are insensitive to high salt concentrations, suggesting a
      nonelectrostatic component to the interaction between ferlin C2 domains and lipid
      bilayers. Together, the data indicate that dysferlin, otoferlin, and myoferlin do
      not merely passively adsorb to membranes but actively sculpt lipid bilayers,
      which would result in highly curved or distorted membrane regions that could
      facilitate membrane fusion, membrane fission, or recruitment of other membrane
      trafficking proteins. 

PMID- 23859475
TI  - The triple challenge of recruiting older adults with dementia and high medical
      acuity in skilled nursing facilities.
AB  - PURPOSE: To describe strategies, culled from experience, for responding to
      several recruitment challenges in an ongoing randomized clinical trial of
      delirium in persons with dementia. ORGANIZING CONSTRUCT: Delirium in people with
      dementia is common across all cultures. Little research supports the use of
      specific interventions for delirium. Recruitment of an adequate sample is
      critical to the validity of findings from intervention studies that form the
      foundation for evidence-based practice. METHODS: The trial referenced in this
      article tests the efficacy of cognitive stimulation for resolving delirium in
      people with dementia. Participants are recruited at the time of admission to one
      of eight community-based skilled nursing facilities (SNFs). Eligible participants
      are 65 years of age or older and community dwelling, and have a diagnosis of
      dementia and delirium. Recruitment challenges and strategies were identified
      during weekly team meetings over a 2-year period. FINDINGS: Recruitment
      challenges include factors in the external and internal environment and the
      participants and their families. Strategies that address these challenges include
      early site evaluation and strong communication approaches with staff,
      participants, and families. CONCLUSIONS: The recruitment of an adequate sample of
      acutely ill older adults with dementia in SNFs can pose a challenge to
      investigators and threaten the validity of findings. Recruitment strategies that
      help improve the validity of future studies are described. CLINICAL RELEVANCE:
      Worldwide, over 100 million people will have dementia by 2050, placing them at
      increased risk for delirium. Recruitment strategies that improve the quality of
      nursing research and, by extension, the care and prevention of delirium in older
      adults with dementia during rehabilitation in SNFs are greatly needed.

PMID- 23859476
TI  - Probing the interaction of individual amino acids with inorganic surfaces using
      atomic force spectroscopy.
AB  - This article describes single-molecule force spectroscopy measurements of the
      interaction between individual amino acid residues and inorganic surfaces in an
      aqueous solution. In each measurement, there is an amino acid residue, lysine,
      glutamate, phenylalanine, leucine, or glutamine, and each represents a class of
      amino acids (positively or negatively charged, aromatic, nonpolar, and polar).
      Force-distance curves measured the interaction of the individual amino acid bound
      to a silicon atomic force microscope (AFM) tip with a silcon substrate, cut from
      a single-crystal wafer, or mica. Using this method, we were able to measure low
      adhesion forces (below 300 pN) and could clearly determine the strength of
      interactions between the individual amino acid residues and the inorganic
      substrate. In addition, we observed how changes in the pH and ionic strength of
      the solution affected the adsorption of the residues to the substrates. Our
      results pinpoint the important role of hydrophobic interactions among the amino
      acids and the substrate, where hydrophobic phenylalanine exhibited the strongest
      adhesion to a silicon substrate. Additionally, electrostatic interactions also
      contributed to the adsorption of amino acid residues to inorganic substrates. A
      change in the pH or ionic strength values of the buffer altered the strength of
      interactions among the amino acids and the substrate. We concluded that the
      interplay between the hydrophobic forces and electrostatic interactions will
      determine the strength of adsorption among the amino acids and the surface.
      Overall, these results contribute to our understanding of the interaction at the
      organic-inorganic interface. These results may have implications for our
      perception of the specificity of peptide binding to inorganic surfaces.
      Consequently, it would possibly lead to a better design of composite materials
      and devices. 

PMID- 23859477
TI  - F + (H2O)2 reaction: the second water removes the barrier.
AB  - In light of controversy concerning the classical barrier for the F + H2O -> HF +
      OH reaction, higher level theoretical methods are applied. Both aug-cc-pV5Z
      CCSD(T) and cc-pVQZ full CCSDT methods predict a low classical barrier of about 2
      kcal/mol. For the analogous water dimer reaction, the presence of the second
      water molecule erases this barrier entirely. An entrance complex F...(H2O)2 is
      found lying 7.3 kcal/mol below separated F + (H2O)2. A barrier follows this
      complex on the reaction coordinate, but lying 3.1 kcal/mol below the reactants.
      There is also an exit complex HF...H2O3 lying 11.0 kcal/mol below the separated
      products HF + H2O3. Thus the reactions of atomic fluorine with the water monomer
      and dimer are qualitatively different. 

PMID- 23859478
TI  - Anomalous optical phonon splittings in sliding bilayer graphene.
AB  - We study the variations of electron-phonon coupling and their spectroscopic
      consequences in response to the sliding of two layers in bilayer graphene using
      first-principles calculations and a model Hamiltonian. Our study shows that the
      long wavelength optical phonon modes change in a sensitive and unusual way
      depending on the symmetry as well as the parity of sliding atomic structures and
      that, accordingly, Raman- and infrared-active optical phonon modes behave
      differently upon the direction and size of the sliding. The renormalization of
      phonon modes by the interlayer electronic coupling is shown to be crucial to
      explain their anomalous behavior upon the sliding. Also, we show that the crystal
      symmetry change due to the sliding affects the polarized Stokes Raman scattering
      intensity, which can be utilized to detect tiny misalignment of graphene layers
      using spectroscopic tools. 

PMID- 23859479
TI  - Pentose phosphate pathway activity: effect on in vitro maturation and oxidative
      status of bovine oocytes.
AB  - The relationship between pentose phosphate pathway (PPP) activity in cumulus
      oocyte complexes (COCs) and oxidative and mitochondrial activity in bovine
      oocytes was evaluated with the aim of analysing the impact of two inhibitors
      (NADPH and 6-aminonicotinamide (6-AN)) and a stimulator (NADP) of the key enzymes
      of the PPP on the maturation rate, oxidative and mitochondrial activity and the
      mitochondrial distribution in oocytes. The proportion of COCs with measurable PPP
      activity (assessed using brilliant cresyl blue staining), glucose uptake, lactate
      production and meiotic maturation rate diminished when 6-AN (0.1, 1, 5 and 10mM
      for 22h) was added to the maturation medium (P<0.05). The addition of NADPH did
      not modify glucose uptake or lactate production, but reduced PPP activity in COCs
      and meiotic maturation rates (P<0.05). The presence of NADP (0.0125, 0.125, 1.25
      and 12.5mM for 22h of culture) in the maturation medium had no effect on PPP
      activity in COCs, glucose uptake, lactate production and meiotic maturation rate.
      However, in the absence of gonadotropin supplementation, NADP stimulated both
      glucose uptake and lactate production at 12.5mM (the highest concentration
      tested; P<0.05). NADP did not modify cleavage rate, but decreased blastocyst
      production (P<0.05). During IVM, oocyte oxidative and mitochondrial activity was
      observed to increase at 15 and 22h maturation, which was also related to
      progressive mitochondrial migration. Inhibiting the PPP with 6-AN or NADPH led to
      reduced oxidative and mitochondrial activity compared with the respective control
      groups and inhibition of mitochondrial migration (P<0.05). Stimulation of the PPP
      with NADP increased oxidative and mitochondrial activity at 9h maturation
      (P<0.05) and delayed mitochondrial migration. The present study shows the
      significance of altering PPP activity during bovine oocyte IVM, revealing that
      there is a link between the activity of the PPP and the oxidative status of the
      oocyte. 

PMID- 23859480
TI  - Modulating effect of COMT genotype on the brain regions underlying proactive
      control process during inhibition.
AB  - INTRODUCTION: Genetic variability related to the catechol-O-methyltransferase
      (COMT) gene (Val(158)Met polymorphism) has received increasing attention as a
      possible modulator of cognitive control functions. METHODS: In an event-related
      functional magnetic resonance imaging (fMRI) study, a modified version of the
      Stroop task was administered to three groups of 15 young adults according to
      their COMT Val(158)Met genotype [Val/Val (VV), Val/Met (VM) and Met/Met (MM)].
      Based on the theory of dual mechanisms of control (Braver et al., 2007), the
      Stroop task has been built to induce proactive or reactive control processes
      according to the task context. RESULTS: Behavioral results did not show any
      significant group differences for reaction times but Val allele carriers
      individuals are less accurate in the processing of incongruent items. fMRI
      results revealed that proactive control is specifically associated with increased
      activity in the anterior cingulate cortex (ACC) in carriers of the Met allele,
      while increased activity is observed in the middle frontal gyrus (MFG) in
      carriers of the Val allele. CONCLUSION: These observations, in keeping with a
      higher cortical dopamine level in MM individuals, support the hypothesis of a
      COMT Val(158)Met genotype modulation of the brain regions underlying proactive
      control, especially in frontal areas as suggested by Braver et al.

PMID- 23859481
TI  - Karyotyping of diffuse large B-cell lymphomas: loss of 17p is associated with
      poor patient outcome.
AB  - BACKGROUND: Cytogenetic studies of patients with diffuse large B-cell lymphoma
      (DLBCL) have revealed a large spectrum of chromosomal abnormalities, some of
      which may be clinically relevant. We wanted to evaluate possible associations
      between commonly acquired chromosome aberrations and prognosis in a large cohort
      of patients. METHODS: All patients with DLBCL treated at our center during 1999
      2010 with an abnormal G-banding karyotype determined on cells short-term cultured
      from diagnostic biopsies were included. Detailed information on staging,
      treatment, and outcome was available for all patients. RESULTS: Of the 110
      patients available for analysis, there were 48 deaths and 27 relapses after a
      median follow-up of 4.5 yr. Eleven different chromosomal abnormalities were
      detected in more than ten percent of patients. Of those, only loss of 17p,
      including the TP53 tumor suppressor gene, was significantly associated with
      inferior long-term prognosis. Five year overall and progression-free survival
      frequencies were 32% and 27% for patients with loss of 17p and 67% and 59% in
      patients without this abnormality. CONCLUSION: In a relatively large cohort of
      patients with DLBCL analyzed by chromosome banding, loss of 17p was the only
      chromosomal abnormality associated with inferior survival in uni- and
      multivariate analysis.

PMID- 23859482
TI  - Metabolic concentration of lipid soluble organochlorine burdens in the blubber of
      southern hemisphere humpback whales through migration and fasting.
AB  - Southern hemisphere humpback whales undertake the longest migrations and
      associated periods of fasting of any mammal. Fluctuations in lipid energy stores
      are known to profoundly affect the toxicokinetics of lipophilic organochlorine
      compound (OC) burdens. Results from blubber biopsy sampling of adult, male
      humpback whales at two time points of the annual migration journey revealed
      dramatic concentration effects for the majority of OC compounds. The observed
      concentration effect was, however, not linear with measured average blubber lipid
      loss indicating significant redistribution of OCs and hence the importance of
      alternate lipid depots for meeting the energetic demands of the migration
      journey. Applying lipophilic OC burdens as novel tracers of whole-body lipid
      dynamics, the observed average concentration index suggests an average individual
      weight loss of 13% over 4 months of the migration journey. This value is based
      upon lipid derived energy and is in good agreement with previous weight
      prediction formulas. Notably, however, these estimates may greatly underestimate
      individual weight loss if significant protein catabolism occurs. Biomagnification
      factors between migrating southern hemisphere humpback whales and their principal
      prey item, Antarctic krill, closely resembled those of baleen whales feeding on
      herbivorous zooplankton in the Arctic. This study emphasizes the importance of
      considering prolonged periods of food deprivation when assessing chemical risks
      posed to wildlife. This is of particular importance for Polar biota adapted to
      extremes in ecosystem productivity. 

PMID- 23859483
TI  - Are professional soccer players at higher risk for ALS?
AB  - Since the observation of several deaths from amyotrophic lateral sclerosis (ALS)
      among Italian professional soccer players, an association between ALS and soccer
      has been postulated, supported by high rates of morbidity and mortality risks in
      large cohorts of professionals. Several factors may explain this. A history of
      repeated (head) injuries is reported more frequently by ALS patients than by
      individuals with other clinical conditions. An association between exercise and
      ALS has also been suggested, but results in animals and humans are conflicting.
      Some clinical and experimental observations suggest a relation between ALS and
      use of substances such as non-steroidal anti-inflammatory agents, and dietary
      supplements including branched-chain amino acids. Although Italian soccer players
      may be at higher risk of ALS than players in other countries, and higher than
      expected disease frequency seems soccer-specific, increased attention by the
      Italian lay press is an explanation that cannot be excluded. However, growing
      evidence points to the possibility that soccer players with ALS are susceptible
      individuals who develop the disease in response to combinations of environmental
      factors. Only cohort and case-control studies carried out with the same design in
      different European countries can provide a definite answer to this suspected but
      still unconfirmed association.

PMID- 23859484
TI  - Ventral and dorsal visual pathways support auditory motion processing in the
      blind: evidence from electrical neuroimaging.
AB  - Blindness induces processes of neural plasticity, resulting in recruitment of the
      deafferentated visual areas for non-visual sensory functions. These processes are
      related to superior abilities of blind compared with sighted individuals for
      specific auditory and tactile tasks. Recently, an exceptional performance of the
      blind has been demonstrated for auditory motion perception, with a minimum
      audible movement angle that was half that of sighted controls (J. Lewald (2013)
      Neuropsychologia, 51, 181-186). The present study revealed an
      electrophysiological correlate of this finding by analysing the so-called motion
      onset response, a prominent auditory-evoked potential to the onset of motion. The
      cN1 component of this response, appearing about 170 ms after motion onset, was
      two times higher in amplitude for blind compared with matched sighted control
      subjects. At the time of the cN1, electrical neuroimaging using sLORETA revealed
      stronger activation in blind than sighted subjects primarily in ventral visual
      areas (V1v, V2v, VP, V4v) of the right occipital lobe. Activation was also
      obtained in middle temporal area V5. These findings suggest that blindness
      results in stronger involvement of both non-motion areas of the ventral visual
      stream and motion areas of the dorsal visual stream in processing of auditory
      motion at the same point in time after motion onset. This argues against the view
      that visual motion areas, such as area V5, are preferentially recruited for
      auditory motion analysis in the blind. Rather, cross-modal reorganization of
      cortical areas induced by blindness seems to be largely independent of the
      specific visual functions of the same areas in sighted persons. 

PMID- 23859485
TI  - Transient corneal endothelial changes following accelerated collagen cross
      linking for the treatment of progressive keratoconus.
AB  - PURPOSE: To evaluate the corneal endothelial changes following accelerated
      collagen cross-linking (CXL) for the treatment of progressive keratoconus.
      METHODS: Thirty-six consecutive progressive keratoconus patients who received
      accelerated CXL treatment were enrolled in the study. Following de
      epithelization, isoosmolar 0.1% riboflavin solution without dextran was instilled
      every 3 min throughout the 30 min of soaking time before the 5 min of 18 mW/cm(2)
      UVA irradiation and every 2 min during the UVA irradiation. Corneal specular
      microscopy was performed on both treated and fellow eyes of each patient
      preoperatively, in the first week, and in the first, third and sixth month
      postoperatively. RESULTS: There were significant differences in endothelial cell
      density (ECD), percentages of hexagonality (6A) and coefficient of variation of
      endothelial cell area (CV) in the first week and first month postoperatively in
      the treated eyes when compared to their preoperative values and also to the first
      week and first month ECD, 6A and CV values of the non-operative eyes. ECD
      returned to the preoperative values at sixth month whereas 6A and CV returned to
      the preoperative values at third month. CONCLUSION: Our results suggested that
      there may be transient changes in human corneal endothelium following accelerated
      UVA/riboflavin CXL. Resolution of these changes during the follow-up may indicate
      a safe recovery. However, the treatment guidelines for accelerated CXL including
      irradiance level and soaking time should be clearly established to minimize the
      toxic effects of the treatment.

PMID- 23859486
TI  - Consumer perceptions of medication warnings about driving: a comparison of French
      and Australian labels.
AB  - OBJECTIVE: Little research has examined user perceptions of medication warnings
      about driving. Consumer perceptions of the Australian national approach to
      medication warnings about driving are examined. The Australian approach to
      warning presentation is compared with an alternative approach used in France.
      Visual characteristics of the warnings and overall warning readability are
      investigated. Risk perceptions and behavioral intentions associated with the
      warnings are also examined. METHOD: Surveys were conducted with 358 public
      hospital outpatients in Queensland, Australia. Extending this investigation is a
      supplementary comparison study of French hospital outpatients (n = 75). RESULTS:
      The results suggest that the Australian warning approach of using a combination
      of visual characteristics is important for consumers but that the use of a
      pictogram could enhance effects. Significantly higher levels of risk perception
      were found among the sample for the French highest severity label compared to the
      analogous mandatory Australian warning, with a similar trend evident in the
      French study results. The results also indicated that the French label was
      associated with more cautious behavioral intentions. CONCLUSION: The results are
      potentially important for the Australian approach to medication warnings about
      driving impairment. The research contributes practical findings that can be used
      to enhance the effectiveness of warnings and develop countermeasures in this
      area. Hospital pharmacy patients should include persons with the highest level of
      likelihood of knowledge and awareness of medication warning labeling. Even in
      this context it appears that a review of the Australian warning system would be
      useful particularly in the context of increasing evidence relating to associated
      driving risks. Reviewing text size and readability of messages including the
      addition of pictograms, as well as clarifying the importance of potential risk in
      a general community context, is recommended for consideration and further
      research.

PMID- 23859487
TI  - Both red and blond orange juice intake decreases the procoagulant activity of
      whole blood in healthy volunteers.
AB  - AIM: Numerous epidemiological studies suggest that exposure to flavonoid-rich
      fruits has beneficial influence on risk factors for cardiovascular disease. We
      investigated whether intake of orange juice (OJ) could affect whole blood (WB)
      procoagulant activity. METHODS: 17 healthy subjects (aged 31 +/- 1.5 SEM 10
      males) were randomized to receive, according to a cross-over design, either red
      or blond OJ, enriched or free of anthocyanins, respectively. After one week run
      in period on a controlled diet, the subjects were randomly allocated to receive
      either type of OJ for 4 weeks, with a 4-week wash-out period. Venous blood was
      collected on citrate before and at the end of each treatment period. WB was
      incubated with or without an inflammatory stimulus (tumor necrosis factor-alpha
      or bacterial endotoxin LPS). Procoagulant activity was evaluated by a one-stage
      clotting assay. Tissue factor (TF) and TF pathway inhibitor (TFPI) were measured
      in plasma by ELISA. RESULTS: Intake of either type of OJ caused a prolongation of
      unstimulated and stimulated WB clotting times, without any difference between the
      two treatments. Intake of OJ did not modify TF levels. On the contrary, an
      increase in circulating TFPI antigen was detected following either treatment.
      CONCLUSIONS: Orange juice intake by healthy volunteers decreases procoagulant
      activity, possibly through mechanisms independent of its anthocyanin content.

PMID- 23859488
TI  - Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose
      cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment.
AB  - AIMS: Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2)
      inhibitor that inhibits renal glucose reabsorption and is being investigated for
      the treatment of type 2 diabetes mellitus (T2DM). METHODS: In this open-label
      study, the effect of renal impairment on the pharmacokinetics, pharmacodynamics
      and safety of a 50 mg dose of empagliflozin was investigated in 40 subjects,
      grouped according to estimated glomerular filtration rate (eGFR). RESULTS:
      Maximum empagliflozin plasma concentrations were similar in subjects with normal
      renal function and renal impairment. Area under the empagliflozin concentration
      time curve (AUC0 -infinity ) values increased by approximately 18, 20, 66 and 48%
      in subjects with mild, moderate, severe renal impairment and renal failure/end
      stage renal disease (ESRD), respectively, in comparison to healthy subjects. This
      was attributed to decreased renal clearance (CLR ). Urinary glucose excretion
      (UGE) decreased with increasing renal impairment and correlated with decreased
      eGFR and CLR . Empagliflozin was well tolerated, with no increase in adverse
      events associated with renal impairment. CONCLUSIONS: Renal insufficiency
      resulted in decreased CLR of empagliflozin, moderately increased systemic
      exposure and decreased UGE. A single 50 mg dose of empagliflozin was well
      tolerated in subjects with normal renal function and any degree of renal
      impairment. The pharmacokinetic results of this study indicate that no dose
      adjustment of empagliflozin is required in patients with renal impairment.

PMID- 23859489
TI  - Cocrystals of 10-methylphenthiazine and 1,3-dinitrobenzene: implications for the
      optical sensing of TNT-based explosives.
AB  - The evaporation of an ethanol solution containing an equimolar mixture of 10
      methylphenothiazine and 1,3-dinitrobenzene gave red-purple crystals. The diffuse
      reflection spectrum for the cocrystals showed a low reflectance from the UV
      through the visible spectrum until the reflectance increased at the red end of
      the visible spectrum. The crystal structure showed alternating pi stacking of the
      electron-rich 10-methylphenothiazine and the electron-poor 1,3-dinitrobenzene.
      There were also hydrogen bonding interactions between the nitro groups from 1,3
      dinitrobenzene and the aromatic hydrogen atoms from 10-methylphenothiazine. The
      infrared spectrum showed a shift to lower wavenumbers for the symmetric and
      antisymmetric stretching modes for the nitro groups. Thin films containing 10
      methylphenothiazine in polystyrene were exposed to 1,3-dintrobenzene vapor, and
      spectroscopic ellipsometry showed an average increase in the refractive index of
      0.006 through the entire range of wavelengths from 1000 to 300 nm. 

PMID- 23859490
TI  - Purine metabolism during neuronal differentiation: the relevance of purine
      synthesis and recycling.
AB  - Purines are a class of small organic molecules that are essential for all cells.
      They play critical roles in neuronal differentiation and function. Their
      importance is highlighted by several inherited disorders of purine metabolism,
      such as Lesch-Nyhan disease, which is caused by a deficiency of the purine
      salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt). Despite
      the known importance of purines in the nervous system, knowledge regarding their
      metabolism in neurons is limited. In the current studies, purine pools and their
      metabolism were examined in rat PC6-3 cells, a PC12 pheochromocytoma subclone
      that undergoes robust differentiation with nerve growth factor. The results were
      compared with five new independent PC6-3 subclones with defective purine
      recycling because of different mutations affecting HGprt enzyme activity. The
      results demonstrate an increase in most purines and in energy state following
      neuronal differentiation, as well as specific abnormalities when purine recycling
      is lost. The loss of HGprt-mediated purine recycling also is associated with
      significant loss of dopamine and related metabolites in the mutant PC6-3 lines,
      suggesting an important connection between purine and dopamine pathways. These
      results provide insights into how purine pools and metabolism change with
      neuronal differentiation, and how specific enzyme defects may cause neuronal
      dysfunction. Differentiation of dopaminergic PC6-3 cells is accompanied by
      increased purine pools and energy state. The lack of a functional purine
      recycling pathway causes purine limitation in both undifferentiated and
      differentiated cells, as well as profound loss of dopamine content. The results
      imply an unknown mechanism by which intracellular purine levels regulate dopamine
      levels. 

PMID- 23859491
TI  - Patterns of proton pump inhibitor utilization in gastroesophageal reflux disease
      and the effect of restrictions on reimbursement: a nationwide prescription
      database study.
AB  - OBJECTIVE: To assess the drug utilization patterns for proton pump inhibitors
      (PPIs) prescriptions dispensed in periods with and without restrictions on
      reimbursement in a public healthcare system. MATERIAL AND METHODS: Data on all
      PPI prescriptions dispensed for gastroesophageal reflux disease (GERD) was
      retrieved from the Norwegian Prescription Database (NorPD) from 1 January 2004 to
      31 January 2008. PPI utilization patterns were studied in new and current users
      of PPI in periods affected and not affected by a change in prescription policy.
      RESULTS: The policy change resulted in 39% of esomeprazole patients discontinuing
      PPI therapy during a 12-month period while 23% discontinued PPI therapy during a
      period not affected by the policy change. The shift frequency to a different PPI
      was low, 5% and 7% respectively, during periods not affected by policy change.
      Despite a required shift in most esomeprazole patients, 64% still continued on
      esomeprazole. Among the 36% who shifted from esomeprazole to a different PPI, 25%
      subsequently shifted back to esomeprazole. In new PPI users, the proportion of
      esomeprazole users declined from 57% before to 20% after the introduction of the
      policy change. CONCLUSIONS: Despite GERD being a chronic disease in most
      patients, there was a high degree of alteration seen in the utilization patterns
      of PPIs. A high proportion discontinued PPI therapy indicating mild symptoms or
      remission. The switching between different PPIs was low indicating good efficacy
      and tolerability in most patients. The policy change was more effective in new
      PPI users compared with the mandated shift in ongoing esomeprazole users.

PMID- 23859492
TI  - The incidence of acute pancreatitis: impact of social deprivation, alcohol
      consumption, seasonal and demographic factors.
AB  - BACKGROUND: The incidence of acute pancreatitis has increased sharply in many
      European countries and the USA in recent years. AIM: To establish trends in
      incidence and mortality for acute pancreatitis in Wales, UK, and to assess how
      incidence may be linked to factors including social deprivation, seasonal effects
      and alcohol consumption. METHODS: Use of record linked inpatient, mortality and
      primary care data for 10,589 hospitalised cases of acute pancreatitis between
      1999 and 2010. RESULTS: The incidence of acute pancreatitis was 30.0 per 100,000
      population overall, mortality was 6.4% at 60 days. Incidence increased
      significantly from 27.6 per 100,000 in 1999 to 36.4 in 2010 (average annual
      increase = 2.7% per year), there was little trend in mortality (0.2% average
      annual reduction). The largest increases in incidence were among women aged <35
      years (7.9% per year) and men aged 35-44 (5.7%) and 45-54 (5.3%). Incidence was
      1.9 times higher among the most deprived quintile of patients compared with the
      most affluent (3.9 times higher for alcoholic acute pancreatitis and 1.5 for
      gallstone acute pancreatitis). Acute pancreatitis was increased significantly
      during the Christmas and New Year weeks by 48% (95% CI = 24-77%) for alcoholic
      aetiology, but not for gallstone aetiology (9%). Alcoholic admissions were
      increased with higher consumption of spirits and beer, but not wine. CONCLUSIONS:
      The study shows an elevated rate of alcoholic acute pancreatitis during the
      Christmas and New Year period. Acute pancreatitis continues to rise, most rapidly
      for young women, while alcoholic acute pancreatitis is linked strongly with
      social deprivation.

PMID- 23859493
TI  - Performance of transient elastography (TE) and factors associated with
      discordance in non-alcoholic fatty liver disease.
AB  - OBJECTIVE: To determine the accuracy of transient elastography (TE) and factors
      associated with discordance between TE and liver histology in patients with non
      alcoholic fatty liver disease (NAFLD). METHODS: The accuracy of TE was assessed
      and compared with the aspartate aminotransferase-to-platelet ratio index (APRI)
      in patients with histologically proven NAFLD. Factors associated with discordance
      between liver histology and TE were analyzed. RESULTS: Altogether 131 patients
      with a mean age of 49.9 years, including 69 men and 62 women, with NAFLD
      underwent liver stiffness measurement (LSM) by TE. Among all patients, 120
      (91.6%) had a successful LSM with an interquartile to median ratio of 0.15. The
      accuracy of TE in detecting >=F3 and F4 fibrosis, assessed by the area under the
      receiver operating characteristic curve, were 0.77 and 0.95, respectively. The
      sensitivity and specificity of the optimal LSM cut-off values for detecting >=F3
      fibrosis (sensitivity 70.4% and specificity 66.6%) and F4 (sensitivity 87.5% and
      specificity 89.3%) were modest, but better than those of APRI. Discordance
      between TE and histology for fibrosis grading was observed in 22.5% of patients,
      but it could not be explained by body mass index, alanine aminotransferase level,
      the length of the biopsied specimens or the grade of steatosis. CONCLUSION: TE
      plays an important role in the detection of advanced fibrosis and cirrhosis in
      patients with NAFLD and its accuracy does not appear to be influenced by
      components of the disease.

PMID- 23859494
TI  - Reset osmostat in pregnancy: a case report.
AB  - The reset osmostat syndrome, a form of inappropriate antidiuretic hormone
      secretion (SIADH), occurs when the threshold for antidiuretic hormone secretion
      is moved downward. There is evidence to suggest a "reset osmostat phenomenon" in
      normal pregnancies, whereby the average plasma-osmolality is decreased by 5-10
      mOsm/kg. We present a case of a non-physiologic reset osmostat in a pregnant
      patient, thought to be caused by large intracranial arteriovenous malformations
      and intraventricular hemorrhage. The presence of a reset osmostat should be
      suspected in any patient with apparent SIADH who has mild hyponatremia that is
      stable over many days despite variations in sodium and water intake. Therapeutic
      efforts to raise the serum sodium concentration appear to be unnecessary.

PMID- 23859495
TI  - Effect of antioxidant supplementation on digestive enzymes in radiation induced
      intestinal damage in rats.
AB  - PURPOSE: Intestinal mucosa, a rapidly proliferating tissue, is highly sensitive
      to radiation and undergoes apoptosis as a consequence of over generation of
      oxidative free radicals and the lack of the antioxidants. Thus the present study
      was designed to investigate the intestinal damage induced by radiation and to
      study if supplementation of the diet with antioxidant vitamins could ameliorate
      the intestinal damage and its digestive activity, as determined by the expression
      of various border enzymes. MATERIALS AND METHODS: Swiss Albino rats (150-200 g
      body weight) were divided into six groups. Group I: Control untreated; Group II:
      Irradiated; Group III: Irradiated + vitamin A; Group IV: Irradiated + vitamin C;
      Group V: Irradiated + vitamin E; and Group VI: Irradiated + lycopene. Animals
      were exposed to whole body gamma-radiation from (60)Co at the rate of 8 Gy for 15
      min/rat. Intestinal morphology and changes in various digestive enzymes together
      with, DNA damage was studied in six groups and each group consisted of 18
      animals. RESULTS: The gastrointestinal toxicity resulted in malabsorption,
      diarrhoea, weight loss, loss of appetite, abdominal haemorrhage and hair loss.
      The activities of sucrase and alkaline phosphatase were elevated and those of
      lactase, leucine aminopeptidase (LAP) and gamma-glutamyl transpeptidase or
      tranferase (gamma-GTP) were markedly reduced. Antioxidant vitamin A, C or E
      supplementations prevented changes in brush border enzyme activities as compared
      to lycopene administration in rat intestine by radiation exposure. Intestinal
      histology showed that the vitamin supplementation to irradiated rats minimized
      the intestinal damage in rats. CONCLUSION: These findings suggest that the
      epithelial lining of the intestine is highly sensitive to radiation exposure and
      supplementation of antioxidant vitamins is helpful in minimizing the intestinal
      damage and supplementation by vitamin E was most potent in ameliorating the
      intestinal aberrations.

PMID- 23859496
TI  - Isolation and phylogenetic relationships of bat trypanosomes from different
      biomes in Mato Grosso, Brazil.
AB  - In the order Chiroptera, more than 30 trypanosome species belonging to the
      subgenera Herpetosoma, Schizotrypanum, Megatrypanum, and Trypanozoon have been
      described. The species Trypanosoma cruzi , Trypanosoma cruzi marinkellei, and
      Trypanosoma dionisii are the most common in bats and belong to the Schizotrypanum
      subgenus. Bats from 2 different biomes, Pantanal and Amazonia/Cerrado in the
      state of Mato Grosso, Brazil, were evaluated according to the presence of
      trypanosome parasites by means of hemoculture and PCR in primary samples (blood
      samples). A total of 211 bats from 20 different species were caught and the
      trypanosome prevalence, evaluated through hemoculture, was 9.0% (19), 15.5% (13),
      and 4.8% (6) in the municipalities of Confresa (Amazonia/Cerrado biome) and
      Pocone (Pantanal biome). Among the 123 primary samples obtained from the bats,
      only 3 (2.4%) were positive. Phylogenetic analysis using trypanosomatid barcoding
      (V7V8 region of SSU rDNA) identified all the isolates and primary samples as T.
      c. marinkellei. The sequences of the isolates were segregated according to the
      bat host genus or species and suggest that co-evolutionary patterns exist between
      hosts and parasites. Further studies in different Brazilian regions and biomes
      need to be conducted in order to gain real understanding of the diversity of
      trypanosomes in bats.

PMID- 23859497
TI  - Effect of surfactant type and redox polymer type on single-walled carbon nanotube
      modified electrodes.
AB  - Electrodes modified with single-walled carbon nanotubes (SWNTs) offer a number of
      attractive properties for developing novel electrochemical sensors. A common
      method to immobilize SWNTs onto the electrode surface is by placing a droplet of
      a SWNT suspension onto the electrode surface and allowing the solvent to
      evaporate. In order to maximize the properties of individual SWNTs, surfactants
      are normally present in these suspensions to provide stable and homogeneous SWNT
      dispersions. In this study we investigated the effect of different surfactants on
      the electrochemical and enzymatic performance of SWNT modified glassy carbon
      electrodes (GCEs). Amperometic biosensors for glucose were fabricated by a two
      step procedure. In the first step, SWNT films were deposited onto GCEs by
      solution casting suspensions of SWNTs in water, Triton X-100, Tween 20, sodium
      cholate or sodium dodecylbenzenesulfonate (NaDDBS). In the second step, hydrogels
      containing a redox polymer and the enzyme, glucose oxidase (GOX), were deposited
      and cross-linked onto the SWNT-modified GCE. Three different redox polymers were
      tested: 3-ferrocenylpropyl-modified LPEI, (Fc-C3-LPEI), 6-ferrocenylhexyl
      modified LPEI, (Fc-C6-LPEI), and poly[(vinylpyridine)Os(bipyridyl)2Cl](2+/3+)(PVP
      Os). Biosensors constructed with SWNT films from suspensions of Triton X-100 or
      Tween 20 generally produced the highest electrochemical and enzymatic responses,
      with Triton X-100 films producing current densities of ~1.7-2.1 mA/cm(2) for the
      three different redox polymers. In contrast, biosensors constructed with SWNT
      films from sodium cholate suspensions resulted in significant decreases in the
      electrochemical and enzymatic response and in some cases showed no enzymatic
      activity. The results with SWNT films from NaDDBS suspensions were dependent upon
      the specific redox polymer used, but in general gave reduced enzymatic responses
      (~0.05-0.4 mA/cm(2)). These results demonstrate the importance of surfactant type
      in fabricating SWNT-modified electrode films.

PMID- 23859499
TI  - Nonmonotonic size dependence in the hole mobility of methoxide-stabilized PbSe
      quantum dot solids.
AB  - We present a facile procedure to fabricate p-type PbSe-based quantum dot solids
      with mobilities as large as 0.3 cm(2) V(-1)s(-1). Upon partial ligand exchange of
      oleate-capped PbSe quantum dots with the methoxide ion, we observe a pronounced
      red shift in the excitonic transition in conjunction with a large increase in
      conductivity. We show that there is little correlation between these two
      phenomena and that the electronic coupling energy in PbSe quantum dot solids is
      much smaller than often assumed. However, we observe for the first time a
      nonmonotonic size dependence of the hole mobility, illustrating that coupling can
      nonetheless be dominant in determining the transport characteristics. We
      attribute these effects to a decrease in charging energy and interparticle
      spacing, leading to enhanced electronic coupling on one hand and enhanced dipole
      interactions on the other hand, which is held responsible for the majority of the
      red shift.

PMID- 23859498
TI  - Structure of mediator of RhoA-dependent invasion (MRDI) explains its dual
      function as a metabolic enzyme and a mediator of cell invasion.
AB  - Metastatic melanoma is among the most intractable cancers to treat; patients show
      resistance to therapy and limited survival time. A critical step in the
      development of metastatic melanoma is the acquisition of invasion and transition
      from thin to thick tumors on the skin, followed by invasion to lymph nodes. Prior
      studies have shown that metastatic melanoma is associated with dysregulation of
      RhoA and enhanced expression of a protein named "mediator of RhoA-dependent
      invasion (MRDI)". Importantly, MRDI is a "moonlighting" enzyme, with two distinct
      functions in melanoma cells. First, MRDI acts as a methylthioribose-1-phosphate
      (MTR-1-P) isomerase, catalyzing a critical step in methionine salvage. Second,
      MRDI promotes and is necessary for melanoma cell invasion, independent of its
      catalytic activity. This paper demonstrates that MtnA, a bacterial MTR-1-P
      isomerase, rescues the methionine salvage function of MRDI, but is unable to
      rescue its role in invasion. The crystal structure of MRDI was solved to a
      resolution of 2.5 A to identify structural elements important for its invasion
      activity. This structure and its comparison with other MTR-1-P isomerases are
      presented, and mutations within a region separate from the MTR-1-P binding site,
      which interfere with invasion, are identified. Thus, structural elements in MRDI
      distal from the MTR-1-P catalytic site are responsible for the invasion
      phenotype. 

PMID- 23859501
TI  - Formation of H2O2 on Au20 and Au19Pd clusters: understanding the structure effect
      on the atomic level.
AB  - Supported gold nanoparticles are promising catalysts for production of H2O2 from
      O2 and H2. Size, structure, and palladium doping effects play the key role in
      activity and selectivity of a gold catalyst. We performed a study of the
      influence of Au20 and Au19Pd structure features on the main steps of H2O2
      formation on the atomic level, using the DFT/PBE approach with relativistic all
      electron basis set. The top, edge, and facet atoms of the tetrahedral Au20
      cluster as well as a palladium atom of Au19Pd located on the top, edge, and facet
      of a tetrahedron have been considered as active sites of steps involved in H2O2
      synthesis. The thermodynamic and kinetic data including Gibbs free energies and
      the activation Gibbs free energies were calculated for the steps determining the
      formation of H2O2 (H(s) + OOH(s) = H2O(2(s)), H2O(2(s)) = H2O(2(g))) and for one
      step decreasing the selectivity (H2O(2(s)) = OH(s) + OH(s)). Gold tends to have
      low activity and high selectivity in H2O2 synthesis regardless of the structure
      of active site. Low coordinated palladium atoms promote H2O2 formation as well as
      its dissociation. Pd on a facet of a cluster facilitates H2O2 production with
      high activity and selectivity.

PMID- 23859502
TI  - A developmental perspective on bulbar involvement in amyotrophic lateral
      sclerosis.

PMID- 23859503
TI  - [Pasteur Institutes, a worldwide network to fight infectious disease].

PMID- 23859504
TI  - [Cellular protein disposal system assists poxvirus genome uncoating].

PMID- 23859505
TI  - [Dual control of motoneuron excitability by serotonin].

PMID- 23859506
TI  - [The brain functional network of children with autism: redundancy and
      disconnection].

PMID- 23859507
TI  - [PD-1 and PDL-1 expression in cancer: significance and prognostic value].

PMID- 23859508
TI  - [TGFbeta, a troublemaker in the adult neural stem cell niche].

PMID- 23859509
TI  - [MiR-142-3p in leukaemogenesis: tumour suppressor or oncomiR?].

PMID- 23859510
TI  - [Interleukin-22: its role in graft-versus-host-disease unraveled].

PMID- 23859511
TI  - [Pharmacological chaperons: a novel therapeutic approach for genetic diseases].

PMID- 23859512
TI  - [Microbial dysbiosis, a new risk factor in colorectal cancer?].

PMID- 23859513
TI  - [Dysbiosis, a new medical concept].

PMID- 23859514
TI  - [TRPV1 in neuropathic pain: from animal models to therapeutical prospects].
AB  - Since its cloning in 1997, functional and structural studies of TRPV1 have led to
      an improvement in our understanding of the mechanisms that underlie the
      transduction of noxious thermal and mechanical stimuli by sensory neurons.
      Because of its role in inflammatory processes and nociceptive pathways, TRPV1 has
      become an important target for neuropathic pain relief. Models of painful small
      fiber sensory neuropathy were developed and several laboratories have progressed
      in the conception of TRPV1 agonists and antagonists. Patch and cream containing
      capsaicin, the most famous TRPV1 agonist, are commercialized to relieve
      neuropathic pain. Others agonists and TRPV1 antagonists are tested in clinical
      trials and new agents, "TRPV1 modulators", with fewer side effects are currently
      developed in experimental studies. 

PMID- 23859515
TI  - [Pulmonary arterial hypertension: a flavor of autoimmunity].
AB  - It is admitted that autoimmunity results from a combination of risks such as
      genetic background, environmental triggers, and stochastic events. Pulmonary
      arterial hypertension (PAH) shares with the so-called prototypic autoimmune
      diseases, genetic risk factors, female predominance and sex hormone influence,
      association with other chronic inflammatory and autoimmune diseases, defects in
      regulatory T cells function, and presence of autoantibodies. Case reports have
      been published indicating the beneficial effect of some immunosuppressive and
      anti-inflammatory therapies in PAH, supporting the potential role of immune
      mechanisms in the pathophysiology of the disease. In this review, we discuss the
      current knowledge on autoimmune mechanisms operating in PAH, especially mounting
      a local autoimmune response inside the pulmonary tissue, namely pulmonary
      lymphoid neogenesis. A better understanding of the role of autoimmunity in
      pulmonary vascular remodelling may help develop targeted immunomodulatory
      strategies in PAH. 

PMID- 23859516
TI  - [Role of cyclic nucleotide phosphodiesterases type 3 and 4 in cardiac excitation
      contraction coupling and arrhythmias].
AB  - Cyclic nucleotide phosphodiesterases (PDE) represent a superfamily of enzymes
      specialised in the degradation of cAMP and cGMP. In heart, PDE3 and PDE4 are the
      two major families involved in the regulation of cAMP levels and the control of
      inotropism. Both families are encoded by several genes, and the recent analysis
      of the cardiac phenotype of mice lacking these different genes provided new
      insights into the way they regulate excitation-contraction coupling (ECC). In
      particular, these studies emphasize the local character of ECC regulation by PDE,
      as well as the role of these PDE in maintaining calcium homeostasis and
      preventing cardiac arrhythmias. 

PMID- 23859517
TI  - [Application of the musculo-skeletal modelling software lhpFusionBox to a
      paleoanthropological problem: the Spyrou Neandertal moves!].
AB  - LhpFusionBox is a program originally designed for biomechanical and clinical
      studies relating to the musculoskeletal system of anatomically modern humans
      (AMH). The program has recently been adapted for paleontological purposes and
      used to reconstruct and biomechanically analyse a fossil hominid. There is no
      complete Neandertal skeleton in the fossil record. The aim of the study was to
      reconstruct a complete three-dimensional (3D) model of a Neandertal using the
      relatively complete Spy II Neandertal and to conduct biomechanical feasibility
      studies on the knee and hamstring moment arms of the skeleton. Different
      Neandertal specimens were scaled to the size of Spy II to replace incomplete or
      missing bones. Biomechanical feasibility studies performed on the knee seem to
      show that Neandertal and AMHh gait is similar and Neandertals were shown to have
      larger moment arms in the hamstring muscles, which would have given them a
      mechanical advantage. The complete Neandertal was printed in 3D and used as the
      base to create the artistic model of "Spyrou" housed at l'Espace de l'Homme de
      Spy (EHoS) museum. 

PMID- 23859518
TI  - [Gastrointestinal stromal tumors (GIST): at the forefront of targeted therapies].
AB  - Although gastrointestinal stromal tumors (GIST) are the most frequent sarcomas,
      they were usually not diagnosed before 1998. GIST derive from interstitial cells
      of Cajal, and may develop along the digestive tract, mainly from stomach and
      small intestine. GIST are characterized by the expression of KIT (CD117), and
      mutations KIT or PDGFRA are present in 85 % of cases. More than 150 different
      types of mutations have been reported. They are responsible for a constitutive
      activation of these tyrosine kinase receptors, in absence of their specific
      ligand. Detection of these mutations may help to confirm the diagnosis or to
      evaluate the prognosis. The mutations also have a predictive value. Indeed
      patients with metastatic GIST and duplication within exon 9 of KIT deserve to
      receive twice the dose of imatinib, while GIST with PDGFRA p.D842 V mutation are
      resistant to this drug. This review presents the main characteristics of GIST,
      and focus on the important insights of studies on GIST and their cell models in
      the field of oncology. 

PMID- 23859519
TI  - [DNA analysis in the anthropological approach of ancient populations].
AB  - The authors highlight the opportunities to reconstruct the human Eurasian steppe
      migration movements with the analyses of nuclear DNA markers (short tandem
      repeats on autosomal DNA and on the Y chromosome) as well as mitochondrial DNA
      markers. They studied 26 ancient human samples from the Krasnoyarsk area
      (Southern Siberia). The specimens were dated from the middle of the second
      millennium BC to the fourth century AD. The Y chromosome and the mitochondrial
      analyses revealed that few of them seem to be related matrilineally or
      patrilineally, but all subjects belong to Y haplogroup R1a1a-M17 which is known
      as a marker of the eastward migration of the early Indo-Europeans. Their results
      are in accordance with the hypothesis that at the Bronze and Iron Ages south
      Siberia was settled predominantly by European subjects suggesting an eastward
      migration of kurgan people across the Russo-Kazakh steppe. The single nucleotide
      polymorphisms (SNP) analyses on the physical traits indicate that the ancient
      studied specimens were blue or green eyed, fair skinned and light-haired. 

PMID- 23859520
TI  - [The international network of Pasteur Institutes - bringing research at the heart
      of endemic areas].

PMID- 23859521
TI  - [When the East meets the West for a better public health].

PMID- 23859522
TI  - [Plasmodium falciparum susceptibility to antimalarial drugs: global data issued
      from the Pasteur Institutes international network].
AB  - Malaria research units within the Institut Pasteur international network (RIIP
      Palu) located in Africa, in South-East Asia and in South America, work for many
      years in close collaboration with the National malaria control programmes.
      Relying on technical platforms with well-equipped laboratories and scientific
      expertise, they are at the forefront of research on the antimalarial drug
      resistance by working together for training young scientists and developping
      similar protocols allowing comprehensive comparisons. Including fundamental and
      operational researches, they conduct regional and international projects which
      aim (1) to detect the emergence of antimalarial drugs resistant parasites and to
      evaluate their spatio-temporal distribution, (2) to develop in vitro and
      molecular tools, (3) to identify epidemiological factors involved in the
      emergence and the spread of antimalarial drugs resistant parasites and (4) to
      understand the molecular and cellular mechanisms implicated in resistance. In
      this review, will be presented methodological approaches and data obtained since
      2000. 

PMID- 23859523
TI  - [In the era of the Royal Society of Medicine].
AB  - In the May 2013 issue of medecine/sciences, the Rob Laffecteur complained about
      the constraints imposed by the Societe Royale de Medecine in 1779, bearing on the
      labelling of remedies. Though, he did take advantage of the evaluation from an
      advertising point of view; though in this prospect he diverted his evaluation's
      report, in order to present it in a flattering manner. The Societe Royale de
      Medecine was founded in 1778; its mission was to cover everything that had to do
      with public healthcare. Active, age-old and competent, it was submitted to many
      of contemporary issues that we are facing nowadays in the matter of medicines'
      evaluation, which is based on a rigorous scientific evaluation, itself based on
      knowledge's state-of-the-art. 

PMID- 23859524
TI  - [Towards the perfect child].
AB  - Sequencing technology now makes possible non-invasive prenatal diagnosis, and may
      soon allow detailed examination of the embryo genome from analysis of a single
      cell. These positive developments that avoid potentially dangerous procedures
      also raise the possibility of choosing the "best" embryo on potentially frivolous
      criteria. 

PMID- 23859525
TI  - [Update on the use of active anti-cytokine therapies with kinoid vaccines for the
      treatment of inflammatory diseases].

PMID- 23859526
TI  - [Genome sequencing and genetic mapping to dissect the genetic basis of complex
      traits].

PMID- 23859527
TI  - The epidemiology of human T-cell lymphotropic virus types I and II in Canadian
      blood donors.
AB  - OBJECTIVES: Blood donors in Canada have been tested for Human T-Cell Lymphotropic
      Virus (HTLV) since 1990. We report the epidemiology, risk factors and
      lookback/traceback of HTLV-positive donors/recipients. METHODS: The annual HTLV
      rate was calculated from 1990 to 2010. Residual risk was estimated as the product
      of incidence and window period. Twenty-nine HTLV-positive donors and 116 matched
      controls (ratio 1 : 4) were interviewed about risk factors. For HTLV-positive
      donations, lookback investigations involved identification of all previous
      donations, and attempting to locate and test recipients. Traceback was initiated
      when transfusion transmission was queried for HTLV-positive blood recipients. All
      donors of products that the recipient received were identified, with an attempt
      to locate and test them. RESULTS: The HTLV rate decreased from 9.35 per 100,000
      donations in 1990 to 1.11 in 2010. The residual risk of infection was 1 in 7.6
      million donations. In logistic regression birth overseas (OR 18.7), history of
      sexually transmitted diseases (OR 32.9), sex with unknown background (OR 5.4) and
      blood transfusion (OR 8.9) were significant predictors. In the lookback study, of
      109 HTLV-positive donors, 508 components were transfused, of whom 147 recipients
      were tested and 18 (12%) were positive. All were transfused prior to the
      implementation of donor testing. Twenty-three traceback investigations were
      requested involving 324 transfused untested products,of whom 219 (67.6%) of
      donors were tested and 13 (6%) were positive for HTLV. CONCLUSIONS: With testing
      of the blood supply, the risk from HTLV is very low and while most HTLV-positive
      donors have risk factors, deferrable risk is rare.

PMID- 23859528
TI  - Monoclonal gammopathy of undetermined significance: a new proposal of workup.
AB  - OBJECTIVE: Diagnostic criteria for monoclonal gammopathy of undetermined
      significance (MGUS) require quantification of bone marrow plasma cells (BMPCs)
      and skeletal survey to discriminate between MGUS and multiple myeloma (MM). By
      contrast, recent published guidelines suggest that these procedures could be
      avoided in the presence of serum monoclonal spike (M-spike) of small amount
      (<=1.5 g/dL). Aim of this study is to better quantify the risk of missing a
      diagnosis of MM, not performing bone marrow aspirate and skeletal survey in
      patients with M-spike <= 1.5 g/dL asymptomatic for bone pain. METHODS: We
      reviewed data of 2282 patients consecutively observed from January 1974 to
      December 2010 in our single hematology department. We considered eligible for
      this study 1271 patients with grade <2 NCI bone pain, confirmed to have an MGUS
      or an MM after extensive standardized diagnostic workup including bone marrow
      biopsy, skeletal bone survey and laboratory tests. RESULTS: The risk of finding a
      BMPC infiltration >=10% in patients with an M-spike <= 1.5 g/dL was very low
      (7.3%), although significantly different according to IgH isotype (4.7% for IgG
      vs. 20.5% for IgA). The risk of finding bone lesions with M-spike <= 1.5 g/dL was
      negligible (2.5%), regardless of IgH isotype. CONCLUSION: In asymptomatic
      patients with M-spike of small amount (<=1.5 g/dL): (i) BMPC evaluation may be
      reasonably avoided in patients with IgG M-spike, while should always be part of
      diagnostic workup in the presence of IgA M-spike and (ii) skeletal survey, less
      predictive for MM, should not be routinely indicated irrespective of IgH isotype.

PMID- 23859529
TI  - Extensive browsing by a conventional grazer? Stable carbon isotope analysis
      reveals extraordinary dietary flexibility among Sanga cattle of North Central
      Namibia.
AB  - Intraspecies dietary flexibility, such as variable consumption of graze vs.
      browse in herbivores, has received scant attention on a spatial scale despite
      growing evidence of substantial variability within and among populations,
      especially in bovids. Here, we report on extraordinary differences in cattle diet
      among two communal pasture areas across seasons in northern Namibia: King Nehale
      (KN, open grassland) and Okongo (OK, dense woodland). Percentage C3 browse and C4
      grass consumption was determined from delta(13)C values of dung samples, using a
      Bayesian stable-isotope mixing model (SIAR - stable isotope analysis in R).
      During the wet and early dry season, KN cattle consumed 11 and 19% browse,
      respectively, and the OK cattle consumed 84% browse. At the end of the dry
      season, the browse intake of KN cattle increased to 33% while that of OK cattle
      decreased to 55%. Vegetation structure influenced the graze/browse consumption
      strongly in both areas. A better understanding of this extraordinary dietary
      flexibility is imperative as anthropogenically driven habitat change is projected
      to lead to the extinction of perceived grazing specialists. 

PMID- 23859530
TI  - Effect of early adrenal vein ligation on blood pressure and catecholeamine
      fluctuation during laparoscopic adrenalectomy for pheochromocytoma.
AB  - OBJECTIVE: To define whether previous control of the adrenal vein is a crucial
      procedure in laparoscopic adrenalectomy for pheochromocytoma. METHODS: From
      January 2000 to December 2010, 114 patients with pheochromocytoma who underwent
      laparoscopic adrenalectomy through transperitoneal or retroperitoneal approach
      were included. The patients were divided into 2 groups randomly (group 1:
      dissection after ligation; group 2: dissection before ligation). Blood samples
      for the measurement of catecholamines levels using high performance liquid
      chromatography were taken at the following time points: t1, before anesthesia;
      t2, during manipulation-extraction of pheochromocytoma; t3, after removal of
      pheochromocytoma. The blood pressure fluctuation was recorded. RESULTS:
      Laparoscopic adrenalectomy was successfully performed on 113 patients with 1
      elective open conversion because of dense peritumor adhesions. The operating time
      ranged from 80 to 150 minutes (mean 108, 102 in group 1, 110 in group 2). Mean
      blood loss ranged from 20 to 500 mL (mean 120 mL, 110 in group 1, 125 in group
      2). The concentrations of plasma catecholamines between the 2 groups had no
      statistical differences. The blood pressure fluctuation incidence between the 2
      groups had no marked difference. But the incidence increased with high
      functionary grade, and the difference was significant (P = .043). CONCLUSION:
      This study demonstrated that previous control of the adrenal vein was not a
      determinate factor in dealing with dangerous hypertension during laparoscopic
      adrenalectomies.

PMID- 23859531
TI  - Robotic partial adrenalectomy using indocyanine green dye with near-infrared
      imaging: the initial clinical experience.
AB  - OBJECTIVE: To present the initial clinical experience with robot-assisted partial
      adrenalectomy using indocyanine green dye with near-infrared fluorescence (ICG
      NIRF) imaging. METHODS: Three consecutive patients with solitary adrenal masses
      with worrisome features were referred for treatment. The preoperative workup
      included dedicated axial imaging and adrenal function studies. All patients
      underwent purely robotic partial adrenalectomy with ICG-NIRF guidance. Relevant
      steps of the technique included a transperitoneal approach, gross identification
      of the adrenal gland, administration of 5 mg intravenous ICG, and finally, mass
      resection guided by ICG-NIRF and white light visualization in an effort to
      completely excise the mass while sparing uninvolved adrenal tissue. RESULTS:
      Robotic partial adrenalectomy was successfully performed with negative margins in
      all patients. All masses were hypofluorescent relative to normal adrenal tissue
      with ICG-NIRF and included a pheochromocytoma, lipoadenoma, and follicular
      lymphoid hyperplasia. CONCLUSION: Robotic partial adrenalectomy with
      intraoperative ICG-NIRF is safe and feasible. The addition of ICG-NIRF may help
      mass identification, excision, and promote the use adrenal-sparing surgery.

PMID- 23859533
TI  - Graphene and g-C3N4 nanosheets cowrapped elemental alpha-sulfur as a novel metal
      free heterojunction photocatalyst for bacterial inactivation under visible-light.
AB  - A new class of metal-free heterojunction photocatalysts was prepared by wrapping
      reduced graphene oxide (RGO) and g-C3N4 (CN) sheets on crystals of
      cyclooctasulfur (alpha-S8). Two distinctive structures were fabricated by
      wrapping RGO and CN sheets in different orders. The first was RGO sheets
      sandwiched in heterojunction of CN sheets and alpha-S8 (i.e., CNRGOS8), while the
      second structure was the other way around (i.e., RGOCNS8). Both structures
      exhibited antibacterial activity under visible-light irradiation. CNRGOS8 showed
      stronger bacterial inactivation than RGOCNS8 in aerobic conditions. However,
      RGOCNS8 was more active than CNRGOS8 under anaerobic condition. A possible
      mechanism was proposed to explain the differences between photocatalytic
      oxidative inactivation and reductive inactivation. As a proof-of-concept, this
      work could offer new inroads into exploration and utilization of graphene sheets
      and g-C3N4 sheets cowrapped nanocomposites for environmental applications. 

PMID- 23859532
TI  - Laparoscopic and robotic radical prostatectomy outcomes in obese and extremely
      obese men.
AB  - OBJECTIVE: To evaluate the operative and pathologic outcomes of laparoscopic
      radical prostatectomy and robot-assisted radical prostatectomy in men with
      progressive changes in body mass index (BMI) category. MATERIALS AND METHODS: A
      single-surgeon series of 1023 laparoscopic radical prostatectomy and robot
      assisted radical prostatectomy (mostly extraperitoneal) patients was considered.
      Of these patients, 987 were evaluable. Results were stratified by the World
      Health Organization BMI category. Multivariate linear and logistic regression
      analysis was used to model the operating time, length of stay, positive surgical
      margins, and noncurable cancer. RESULTS: Of the 987 patients, 563 (57%) were
      overweight and 193 (19.6%) were obese. Of the 193 obese patients, 152 (15.4%) had
      a BMI of 30 to <35 kg/m(2) (class I obesity), 28 (2.8%) a BMI of 35 to <40
      kg/m(2) (class II), and 13 (1.3%) a BMI of >=40 kg/m(2) (class III). No
      differences were found in the estimated blood loss, complications, PSM,
      pathologic stage, or biochemical recurrence across the BMI categories (6-month
      median follow-up). However, pelvic lymph node dissection was more commonly
      omitted and the nerve-sparing score was inferior in the obese men. On
      multivariate analysis, a higher BMI was a significant predictor of a longer
      operating time. CONCLUSION: Obese men can safely undergo laparoscopic radical
      prostatectomy or robot-assisted radical prostatectomy, although the ability to
      perform excellent nerve sparing appears to decrease with increasing obesity.
      Nevertheless, obese men can expect perioperative and early oncologic outcomes
      comparable to those of normal weight men without an increased risk of
      perioperative complications.

PMID- 23859534
TI  - Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose
      cotransporter 2 inhibitor, in patients with hepatic impairment.
AB  - AIMS: This open-label, parallel-group study investigated the effect of various
      degrees of hepatic impairment on the pharmacokinetics, safety and tolerability of
      the sodium glucose cotransporter 2 inhibitor empagliflozin. METHODS: Thirty-six
      subjects [8 each with mild, moderate or severe hepatic impairment (Child-Pugh
      classification), and 12 matched controls with normal hepatic function] received a
      single 50 mg dose of empagliflozin. RESULTS: Empagliflozin was rapidly absorbed.
      After reaching peak levels, plasma drug concentrations declined in a biphasic
      fashion. Compared with subjects with normal hepatic function, geometric mean
      ratios (90% confidence interval) of AUC(0-infinity) and C(max) were 123.15%
      (98.89-153.36) and 103.81% (82.29-130.95), respectively, in patients with mild
      hepatic impairment, 146.97% (118.02-183.02) and 123.31% (97.74-155.55),
      respectively, in patients with moderate hepatic impairment, and 174.70% (140.29
      217.55) and 148.41% (117.65-187.23), respectively, in patients with severe
      hepatic impairment. Adverse events, all mild or moderate in intensity, were
      reported in three subjects with moderate hepatic impairment, two subjects with
      severe hepatic impairment and six subjects with normal hepatic function.
      CONCLUSIONS: Empagliflozin was well tolerated in subjects with hepatic
      impairment. Increases in empagliflozin exposure were less than twofold in
      patients with hepatic impairment; therefore no dose adjustment of empagliflozin
      is required in patients with hepatic impairment.

PMID- 23859535
TI  - Topical and subconjunctival ranibizumab (lucentis) for corneal neovascularization
      in experimental rat model.
AB  - PURPOSE: To compare the effectiveness of the topical and subconjunctival (SC)
      ranibizumab treatment in experimental corneal neovascularization (NV) model in
      rats. METHODS: A model of NV was generated by cauterizing right corneas of 30
      Sprague-Dawley rats with silver nitrate. The animals were separated into five
      groups randomly. first group (control group) received topical artificial tear
      drops two times daily while second and third groups received topical ranibizumab
      four times daily at concentrations of 5 mg/mL and 10 mg/mL, respectively. Forth
      and fifth groups were given 0.5 mg/0.05 mL and 1 mg/0.1 mL of SC ranibizumab in
      the 1st, 3rd and 7th days. The measurements (percentage of NV area and number of
      vessels) from digital photographs of the corneas were determined and analyzed
      using analysis software (ImageJ, v1.38). The animals were sacrificed on the 10th
      day and their corneas were subjected to hemotoxylin-eosin histopathological
      staining and antisera against CD34 and von-Willebrand factor to evaluate
      microvascular structures immunohistochemically. RESULTS: The percentage of the
      corneal NV area and number of vessels in all treatment groups was found to be
      significantly lower than the control group. There was no significant difference
      in relation to the percentage of NV area and number of vessels in the treatment
      groups. Score of the corneal edema was determined to be significantly less in the
      groups that undertook treatment. Number of vessels and inflammatory cells were
      significantly lower in the histological and immunohistochemical sections in the
      treated groups than in the control group. In all treatment groups, fibroblast
      intensity was significantly lower than the control group (p = 0.005). CONCLUSION:
      Topical or SC administration of ranibizumab seems to be a promising and effective
      medication in the treatment of corneal NV. Further research is recommended to
      assess the potential side effects and effective dose.

PMID- 23859536
TI  - Fluorescence micro-spectroscopy study of individual photosynthetic membrane
      vesicles and light-harvesting complexes.
AB  - Single-molecule spectroscopy, by getting rid of unwanted ensemble averaging
      effects, has proved to be a very valuable tool in the research of individual
      photosynthetic light-harvesting (LH) complexes. However, to learn about real
      photosynthetic processes the minimal unit to study is a single photosynthetic
      membrane complete with all elements of its machinery. In the present work, the
      fluorescence spectra of excitons in lone intracytoplasmic (IC) photosynthetic
      membrane vesicles of the wild type purple bacterium Rhodobacter sphaeroides that
      involve peripheral (LH2) and core (RC-LH1-PufX) antenna pigment-protein complexes
      were investigated at ambient temperature under continuous-wave laser excitation
      into the Q(x) absorption band of the bacteriochlorophyll-a (BChl) chromophores at
      594 nm. In parallel, the spectra of mutant membrane vesicles occupied by just one
      type of complexes (either LH2 or RC-LH1-PufX) and the spectra of individual
      purified LH2 and RC-LH1-PufX complexes were measured. The fluorescence from full
      IC membranes shows a high sensitivity to excitation intensity, being varied over
      more than four orders of magnitude between 0.1 W/cm(2) and 2 kW/cm(2). At low to
      moderate excitation intensities, the spectra of IC membranes could be well
      reproduced by its component spectra, the ratio of the spectra related to
      peripheral and core complexes being the only adjustable parameter. The spectra of
      both intact chromatophores and individual membrane components recorded over 1-50
      s experimental time frames are robust, strongly suggesting that large spectral
      fluctuations hardly play a role in the functional photosynthetic process. The
      significant, up to 14 times, variation of the LH2 and LH1 emission ratio observed
      in individual IC membranes could be related to variations in the stoichiometric
      ratio of the peripheral and core complexes. Evidence was found for the presence
      of LH2 parts that are detached from efficient energy transfer pathways. Upon
      strong and prolonged illumination, the membrane spectra reveal significant
      permanent modifications. These alterations, which mostly concern peripheral
      antenna complexes, were shown to be due to photo-oxidation of various numbers of
      BChl molecules in the B850 compartment of LH2.

PMID- 23859537
TI  - Selective amination reactions of alpha-nitro aryl and heteroaryl enoates.
AB  - Highly functionalized tetrasubstituted alkenes were obtained by an unexpected
      amination reaction promoted by ethyl nosyloxycarbamate on various alpha-nitro
      aryl and heteroaryl enoates. A nitrene is likely the aminating species
      responsible for the observed insertion reaction leading to (E)-beta-amino alpha
      nitro enoates as the major products, regardless of the substrate configuration.
      The compounds, bearing two nitrogenous functional groups in different oxidation
      states, can be regarded as interesting synthons. In contrast, aziridination was
      observed for alpha-nitro alkyl enoates or beta-nitro allylic alcohols. 

PMID- 23859538
TI  - Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat
      model of peritoneal dialysis.
AB  - BACKGROUND/AIMS: The present study investigated whether Rho-kinase inhibition had
      a therapeutic role on the pathogenesis of peritoneal fibrosis and angiogenesis.
      METHODS: A rat model of peritoneal dialysis was induced by a daily
      intraperitoneal infusion of 4.25% Dianeal. Those rats were treated with Rho
      kinase inhibitor, fasudil. Immunofluorescence, Western blot and RT-PCR were used
      to detect the expression of TGF-beta1, Collagen I, alphaSMA and VEGF in each
      group. Microvessel density (MVD) was measured by immunohistochemistry. Rho-kinase
      activity was determined by western immunoblotting. RESULTS: Rho-kinase was
      activated in the peritoneum of the PD group, which was inhibited by fasudil.
      Compared with PD group, the mRNA and protein expressions of TGF-beta1, alphaSMA
      and Collagen I were significantly downregulated in fasudil treatment groups in a
      dose-dependent manner, and the expression of VEGF and peritoneal MVD was also
      significantly downregulated in fasudil treatment groups in a dose-dependent
      manner. CONCLUSION: The Rho-kinase was activated in the peritoneum of the
      peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can
      remarkably decrease peritoneal fibrosis and angiogenesis.

PMID- 23859539
TI  - Rhabdomyolysis and acute kidney injury secondary to interaction between
      simvastatin and cyclosporine.

PMID- 23859540
TI  - Normalization of kidney dysfunction in normotensive, normo-albuminuric type 2
      diabetes.

PMID- 23859541
TI  - An empirical study of the toxic capsule crisis in China: risk perceptions and
      behavioral responses.
AB  - The outbreak of the toxic capsule crisis during April 2012 aroused widespread
      public concern about the risk of chromium-contaminated capsules and drug safety
      in China. In this article, we develop a conceptual model to investigate risk
      perceptions of the pharmaceutical drug capsules and behavioral responses to the
      toxic capsule crisis and the relationship between associated factors and these
      two variables. An online survey was conducted to test the model, including
      questions on the measures of perceived efficacy of the countermeasures, trust in
      the State FDA (Food and Drug Administration), trust in the pharmaceutical
      companies, trust in the pharmaceutical capsule producers, risk perception,
      concern, need for information, information seeking, and risk avoidance. In
      general, participants reported higher levels of risk perception, concern, and
      risk avoidance, and lower levels of trust in the three different stakeholders.
      The results from the structural equation modeling procedure suggest that
      perceived efficacy of the countermeasures is a predictor of each of the three
      trust variables; however, only trust in the State FDA has a dampening impact on
      risk perception. Both risk perception and information seeking are significant
      determinants of risk avoidance. Risk perception is also positively related to
      concern. Information seeking is positively related to both concern and need for
      information. The theoretical and policy implications are also discussed. 

PMID- 23859542
TI  - C-reactive protein: a marker of neonatal stress?
AB  - AIM: To assess whether blood values of C-reactive protein (CRP) in healthy term
      newborns, are influenced by stress. MATERIAL AND METHODS: Since different types
      of delivery (vaginal delivery [VD], emergency C-section [EMCS] and elective C
      section [ELCS]) are notoriously characterized by different levels of stress for
      the baby, these three groups were used as models of different levels of stress.
      The mean CRP values of the three groups obtained in the first hours of life were
      compared. RESULTS: We retrieved 1012 babies. Median values (3rd-97th ct) were:
      0.05 (0.01-0.46), 0.17 (0.02-1.54), 0.30 (0.04-1.77), 0.43 (0.05-1.31), 0.40
      (0.04-1.13) at 12, 24, 48, 72 and 96 h, respectively. Mean values in babies born
      after VD were statistically higher than those born after C-section, and higher
      CRP values were present in EMCS with respect to ELCS. CONCLUSION: This study
      described normal blood CRP values in a wide population of term babies. An
      influence of the type of delivery on blood CRP is evident, and this may be
      explained by the different amount of perinatal stress induced by anyone of the
      three types of delivery we considered.

PMID- 23859543
TI  - Redefining the role of the quaternary shift in Bacillus stearothermophilus
      phosphofructokinase.
AB  - Bacillus stearothermophilus phosphofructokinase (BsPFK) is a homotetramer that is
      allosterically inhibited by phosphoenolpyruvate (PEP), which binds along one
      dimer-dimer interface. The substrate, fructose 6-phosphate (Fru-6-P), binds along
      the other dimer-dimer interface. Evans et al. observed that the structure with
      inhibitor (phosphoglycolate) bound, compared to the structure of wild-type BsPFK
      with substrate and activator bound, exhibits a 7 degrees  rotation about the
      substrate-binding interface, termed the quaternary shift [Schirmer, T., and
      Evans, P. R. (1990) Nature 343, 140-145]. We report that the variant D12A BsPFK
      exhibits a 100-fold increase in its binding affinity for PEP, a 50-fold decrease
      in its binding affinity for Fru-6-P, but an inhibitory coupling comparable to
      that of the wild type. Crystal structures of the apo and PEP-bound forms of D12A
      BsPFK have been determined (Protein Data Bank entries 4I36 and 4I7E ,
      respectively), and both indicate a shifted structure similar to the inhibitor
      bound structure of the wild type. D12 does not directly bind to either substrate
      or inhibitor and is located along the substrate-binding interface. A conserved
      hydrogen bond between D12 and T156 forms across the substrate-binding subunit
      subunit interface in the substrate-bound form of BsPFK. The variant T156A BsPFK,
      when compared to the wild type, shows a 30-fold increase in PEP binding affinity,
      a 17-fold decrease in Fru-6-P binding affinity, and an estimated coupling that is
      also approximately equal to that of the wild type. In addition, the T156A BsPFK
      crystal structure bound to PEP is reported (Protein Data Bank entry 4I4I ), and
      it exhibits a shifted structure similar to that of D12A BsPFK and the inhibitor
      bound structure of the wild type. The results suggest that the main role of the
      quaternary shift may be to influence ligand binding and not to cause the
      heterotropic allosteric inhibition per se. 

PMID- 23859544
TI  - Disruption of zinc neuromodulation by Abeta oligomers: therapeutic implications.
AB  - So far, therapeutics focusing on reducing levels of amyloid beta for treatment of
      Alzheimer's disease have not been successful in completing clinical trials to
      come to market, suggesting the need of a wider perspective and the consideration
      of novel targets of intervention to slow or halt the progression of this disease.
      One such target is soluble amyloid beta in oligomeric forms, which have been
      demonstrated to bind with high affinity to zinc released during synaptic
      activity. This review considers the interaction of AbetaO and zinc and the role
      of zinc in neurotransmission along with possible neurotoxic effects of this
      interaction. Finally, it also discusses recent experimental data in animal models
      that have translated into potential treatments for AD based on the modulation of
      hyperexcitability and zinc homeostasis.

PMID- 23859545
TI  - Soluble beta amyloid in a continuum from physiology to pathology: searching the
      determinants of its effects and designing new pharmacological treatments.

PMID- 23859546
TI  - The effects of soluble Abeta oligomers on neurodegeneration in Alzheimer's
      disease.
AB  - The neurodegenerative process that defines Alzheimer''s disease (AD) is initially
      characterized by synaptic alterations followed by synapse loss and ultimately
      cell death. Decreased synaptic density that precedes neuronal death is the
      strongest pathological correlate of cognitive deficits observed in AD.
      Substantial synapse and neuron loss occur early in disease progression in the
      entorhinal cortex (EC) and the CA1 region of the hippocampus, when memory
      deficits become clinically detectable. Mounting evidence suggests that soluble
      amyloid-beta (Abeta) oligomers trigger synapse dysfunction both in vitro and in
      vivo. However, the neurodegenerative effect of Abeta species observed on neuronal
      culture or organotypic brain slice culture has been more challenging to mimic in
      animal models. While most of the transgenic mice that overexpress Abeta show
      abundant amyloid plaque pathology and early synaptic alterations, these models
      have been less successful in recapitulating the spatiotemporal pattern of cell
      loss observed in AD. Recently we developed a novel animal model that revealed the
      neurodegenerative effect of soluble low-molecular-weight Abeta oligomers in vivo.
      This new approach may now serve to determine the molecular and cellular
      mechanisms linking soluble Abeta species to neurodegeneration in animals. In
      light of the low efficiency of AD therapies based on the amyloid cascade
      hypothesis, a novel framework, the aging factor cascade hypothesis, is proposed
      in an attempt to integrate the new data and concepts that emerged from recent
      research to develop disease modifying therapies.

PMID- 23859547
TI  - The renin-angiotensin system as a target of novel anticancer therapy.
AB  - The role of the renin-angiotensin system (RAS) in the development of various
      malignancies has recently been extensively examined and, since it has been shown
      to significantly influence many aspect of cancer initiation and progression, the
      idea of RAS-targeted anticancer therapy has arisen. This article reviews the
      mechanisms underlying RAS-induced physiological and pathological responses
      related to cancer biology, including tumor growth, cell proliferation, apoptosis,
      angiogenesis, inflammation, and protein degradation, emphasizing the associated
      cellular transduction schemes activated by main RAS effectors. Also the dual
      nature of RAS-dependent effects, resulting from its complex physiology has been
      commented. Finally, based on the available data from clinical trials and
      experimental studies, the possibilities of the introduction of RAS-modulating
      drugs into standard clinical practice in oncology have been discussed with the
      focus on both, positive and negative effects associated with the administration
      of various classes of pharmaceuticals to cancer patients. 

PMID- 23859548
TI  - Heterocycle-thioacetic acid motif: a privileged molecular scaffold with potent,
      broad-ranging pharmacological activities.
AB  - Privileged structures can bind to multiple targets with high affinity, thus
      aiding the discovery of novel bioactive agents. Heterocycle- thioacetic acid
      derivatives, a group of molecules containing a heterocycle core linked with a
      thioacetic acid-derived fragment, represent an important type of "privileged
      scaffold" possessing a wide spectrum of biological properties. Numerous
      encouraging investigations demonstrated that this privileged structure should be
      extensively exploited for the therapeutic benefits. In view of its predominance,
      and on the basis of our research interest involved in this scaffold, an updated
      and detailed account of the pharmacological properties of heterocycle-thioacetic
      acid derivatives is described in this article. 

PMID- 23859549
TI  - Modulatory activity of soluble beta amyloid on HPA axis function in rats.
AB  - Despite the consolidation of the amyloid hypothesis, the main component of senile
      plaques in Alzheimer's disease (AD), recent findings have led to a conceptual
      shift opening new questions about the potential physiological role of this
      peptide. In addition, soluble beta amyloid (sBA), in transgenic AD model,
      resulted to be increased after chronic and acute stress and alterations in
      cortisol levels have been reported in AD. Impaired hypothalamic pituitary adrenal
      (HPA) axis has been linked to depressive state and, consistently, we have
      previously demonstrated that BA is able to provoke depressive-like profile in
      rats. Here we further analysed the effect of the peptide in behavioural paradigms
      used to study emotional and cognitive response, by using the passive avoidance
      task, for cognitive parameters, and the sucrose preference test (SPT), to
      evaluate anhedonia. Moreover, in order to correlate behavioural with
      neurochemical and neuroendocrinal data, we investigated the effects of the
      peptide on noradrenergic system in amygdala (AMY), prefrontal cortex (PFC) and
      hippocampus (HIPP) along with plasmatic corticosterone and hypothalamic
      corticotrophin releasing factor (CRF). We found that BA-treated animals showed an
      impaired memory consolidation of inhibitory avoidance training, while no effect
      was evident in SPT. These results lead us to hypothesize a different response to
      stress coping behaviour in BA treated rats. Moreover, BA caused a significant
      increase in noradrenaline (NA) in PFC and HIPP, while in AMY was decreased.
      Consistently, we found a significant decrease in plasma corticosterone
      concentrations in BA-treated rats. Taken together, our data suggest that BA
      exerts an inhibitory effect on HPA axis activation.

PMID- 23859550
TI  - Dangerous liaisons between beta-amyloid and cholinergic neurotransmission.
AB  - The review examines the multifaceted interactions between cholinergic
      transmission and beta-amyloid suggesting a continuum in the action of the peptide
      that at low concentrations (picomolar-low nanomolar) may directly stimulate
      nicotinic cholinergic receptor while desensitizing them at increasing
      concentrations (high nanomolar-low micromolar). In addition high beta-amyloid
      concentrations may reduce the synaptic release of several neurotransmitters,
      including glutamate, aspartate, GABA, glycine and dopamine, when the release is
      elicited through cholinergic stimulation but not following depolarization. The
      effect of beta-amyloid has been observed both in vitro and in vivo in at least
      three different brain areas (nucleus accumbens, striatum, hippocampus) suggesting
      that the peptide may exert some general effects even if not all the brain areas
      have been evaluated. In turn the activation of cholinergic receptors may affect
      the amyloid precursor protein processing diverting the metabolism toward non
      amyloidogenic products. These actions, dissociated from those described in the
      case of high beta-amyloid concentrations leading to neurotoxic oligomers, may
      participate to cause dysfunctions in the neurotransmitter activity, in turn
      leading, at least from a theoretical point of view, to early neuropsychiatric
      disturbances in the disease. Complexively these observations underscore novel
      relationships between two main players in Alzheimer's disease pathogenesis that
      are beta-amyloid and cholinergic transmission. Also emerges the inherent
      difficulty of targeting beta-amyloid in a context in which the peptide exerts
      several actions beyond neurotoxicity.

PMID- 23859551
TI  - Immunization against active ghrelin using virus-like particles for obesity
      treatment.
AB  - Ghrelin is a gut hormone that stimulates food intake. In physiological
      conditions, ghrelin plasma levels rise with fasting and decrease after meals.
      Obese individuals have low fasting ghrelin levels that rise after food
      restriction, which is pointed out as a reason for the difficulty in maintaining
      weight loss. Some bariatric surgery procedures prevent rise in ghrelin levels
      with weight loss and this has been hypothesised to contribute to the long-term
      success of the treatment. The main goal of this study was to develop a safe and
      effective anti-ghrelin vaccine for obesity, through the chemical conjugation of
      ghrelin with a virus like particle, namely NS1 protein tubules from the
      Bluetongue Virus (BTV) using a hetero-bifunctional cross linker. Male adult
      C57BL/6 mice, with a normal weight and with diet-induced obesity (DIO), were
      randomized into six weight matched groups (n=6/group) and each group of mice
      received three intra-peritoneal injections with two weeks intervals, containing
      either 75 MUg of ghrelin- NS1 immunoconjugate, 75 MUg of NS1 or PBS. Our data
      show that immunized animals present increasing titres of anti-ghrelin antibodies,
      while their cumulative food intake significantly decreased and energy expenditure
      was significantly enhanced, although there were no significative changes in body
      weight.Vaccinated DIO mice also displayed significant decrease of NPY gene
      expression in the basal hypothalamus reflecting a decrease in central orexigenic
      signals. This study suggests that this anti-ghrelin vaccine has a positive impact
      on energy homeostasis and may be an additional therapeutical tool to be used with
      diet and exercise for obesity treatment. 

PMID- 23859553
TI  - In vivo application of beta amyloid oligomers: a simple tool to evaluate
      mechanisms of action and new therapeutic approaches.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      cerebral accumulation of extracellular amyloid beta (Abeta) and neurofibrillary
      tangles made of hyperphosphorylated tau protein, two main lesions which appear
      sequentially during the disease progression. In the last decade numerous studies
      have proposed small soluble aggregates of Abeta, known as oligomers, as the
      species responsible for synaptic dysfunction, memory loss and neurodegeneration
      typical of AD. In vitro and in vivo experiments have identified Abeta oligomers
      as the elements that can alter synaptic function by a reversible mechanism, which
      gradually becomes permanent when exposure is continuous. Here we show that
      intracerebroventricular (ICV) injection in mice of a solution containing
      specifically Abeta1-42 oligomers substantially affects their memory when tested
      in the novel object recognition task. This acute mouse model enabled us to
      distinguish whether oligomers were affecting specific phases of the memory
      processing. A single injection of Abeta1-42 oligomers before memory consolidation
      abolished information processing, leading to memory impairment, whereas no such
      effects were observed when the injection was done once the information had been
      processed, indicating that the oligomers affect memory consolidation rather than
      retrieval. Beside Abeta1-42, Abeta1-40 oligomers also impaired memory, and both
      isoforms were antagonized by the anti-Abeta4G8 monoclonal antibody. This simple
      and reliable paradigm is useful to investigate the mechanisms through which Abeta
      oligomers interfere with neuronal processes and to test the efficacy of new
      therapeutic approaches specifically against these species. We tested several
      molecules by direct coincubation with Abeta oligomers, ICV injections preceding
      Abeta oligomers, and the systemic treatment with drugs that cross the blood brain
      barrier. We also examined the proposed involvement of cellular prion protein as a
      mediator of the oligomer-induced memory impairment.

PMID- 23859554
TI  - Getting rid of intracellular Abeta- loss of cellular degradation leads to
      transfer between connected neurons.
AB  - The sporadic, late onset form of Alzheimer's disease (AD) shares pathological
      hallmarks with the familial form; however, no clear reason for increased beta
      amyloid (Abeta) generation has been found in the former. It has long been
      speculated that the late onset form of AD is caused by reduced degradation and/or
      clearance of Abeta. Indeed, both intracellular degradation systems, the
      proteasomal and lysosomal systems, have been shown to be defective in AD. Reduced
      proteasome activity increases levels of intracellular and secreted Abeta.
      Furthermore, accumulation of improperly degraded Abeta in the lysosomes causes
      lysosomal disruption and cell death. We recently showed that oligomeric Abeta can
      be transmitted from one neuron to another, which causes neurotoxicity. In both
      the donating and receiving cells, Abeta accumulates in the endo-lysosomal
      compartment. It is possible that ineffective degradation of Abeta causes its
      transfer to neighboring neurons, thereby spreading AD pathology. This review
      summarizes the data underlying the idea of reduced Abeta clearance and subsequent
      Abeta spread in AD, and also suggests new therapeutic methods, which are aimed at
      targeting the degradation systems and synaptic transfer. By enhancing degradation
      of intracellular accumulated Abeta, it can be possible to remove it and avoid
      Abeta-induced neurodegeneration without disturbing the endogenously important
      pool of secreted Abeta. Additionally, drugs targeted to inhibit the spread of
      intracellular toxic Abeta aggregates may also be useful in stopping the
      progression of pathology, without affecting the level of Abeta that normally
      occurs in the brain. 

PMID- 23859552
TI  - Soluble amyloid-beta levels and late-life depression.
AB  - Late-Life Major Depression (LLMD) is a complex heterogeneous disorder that has
      multiple pathophysiological mechanisms such as medical comorbidity, vascular
      related factors and Alzheimer's disease (AD). There is an association between
      LLMD and AD, with LLMD possibly being a risk factor for, or early symptom of AD
      and vascular dementia. Whether depression is an etiologic risk factor for
      dementia, or part of the dementia prodrome remains controversial. AD has a long
      prodromal period with the neuropathologic features of the disease preceding the
      onset of clinical symptoms by as much as 15-20 years. Clinicopathological studies
      have provided robust support for the importance of Abeta42 in the pathogenesis of
      AD, but several other risk factors have also been identified. Given the
      relationship between Abeta42 and AD, a potential relationship between Abeta42 and
      LLMD would improve the understanding of the association between LLMD and AD. We
      reviewed 15 studies that analyzed the relationship between soluble Abeta42 and
      LLMD. For studies looking at plasma and/or cerebrospinal fluid (CSF) levels of
      Abeta42, the relationship between LLMD and soluble Abeta42 was equivocal, with
      some studies finding elevated Abeta42 levels associated with LLMD and others
      finding the opposite, decreased levels of Abeta42 associated with LLMD. It may be
      that there is poor reliability in the diagnosis of depression in late life, or
      variability in the criteria and the scales used, or subtypes of depression in
      late life such as early vs. late onset depression, vascular-related depression,
      and preclinical/comorbid depression in AD. The different correlations associated
      with each of these factors would be causing the inconsistent results for soluble
      Abeta42 levels in LLMD, but it is also possible that these patterns derive from
      disease stage-dependent differences in the trajectory of CSF Abeta42 during older
      age, or changes in neuronal activity or the sleep/wake cycle produced by LLMD
      that influence Abeta42 dynamics.

PMID- 23859555
TI  - Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid
      arthritis and related diseases.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the
      progressive destruction of joint causes morbidity. It is also associated with an
      increased risk of atherosclerosis, which can result in cardiovascular disease and
      mortality. The therapeutic goal is to control the systemic inflammation to obtain
      not only the remission of symptoms, but also improve general state of health.
      Although recent biologic immunosuppressive therapies targeting pro-inflammatory
      cytokines have spawned a paradigm shift regarding the prognosis of RA, these
      therapies possess inherent side effects. Also, early diagnosis of the disease
      remains confounded by uncertainty. While the mechanisms responsible for the onset
      of RA remain unclear, reactive oxygen species (ROS) play a significant role in
      the pathogenesis of RA. ROS play a central role both upstream and downstream of
      NF-kappaB and TNFalpha pathways, which are located at the center of the
      inflammatory response. Among the ROS, the hydroxyl radical is the most harmful,
      and molecular hydrogen (H2) is a selective scavenger for this species. Recently,
      it has been shown that H2 is useful when administered along with the conventional
      therapy in RA as it acts to reduce oxidative stress in the patients. Especially
      in the early stage, H2 showed significant therapeutic potential, which also
      seemed to assist diagnosis and treatment decisions of RA. The possible
      expectations regarding the potential benefits of H2 by reducing the oxidative
      stress, resulting from inflammatory factors, are raised and discussed here. They
      include prevention of RA and related atherosclerosis, as well as therapeutic
      validity for RA. 

PMID- 23859556
TI  - Characterization of the effect of a novel gamma-secretase modulator on Abeta: a
      clinically translatable model.
AB  - Alzheimer's disease (AD) is a slowly progressing disease and the evaluation of
      clinical effects of candidate drugs requires large clinical cohorts as well as
      long treatment trials. There is a great need for central biomarkers and
      translatable pre-clinical models to provide early indication of treatment
      effects. We set out to evaluate the guinea pig as a clinically translatable model
      looking at Abeta peptides. Our data demonstrate homology between beta-amyloid
      (Abeta) peptide pattern in cerebrospinal fluid (CSF) from human and guinea pig.
      To further evaluate the model a novel gamma-secretase modulator was used. Dose
      and time response studies confirm the modulatory properties with a statistically
      significant decrease in relative levels of Abeta1-40, Abeta1-42 and increase in
      Abeta1-37 already one hour after administration. We suggest that the guinea pig
      is a compelling pre-clinical model for evaluating and translating central effects
      on Abeta peptides in CSF after treatment. Further quantitative data are needed to
      confirm our data together with data from clinical trials in order to back
      translate and validate our findings. 

PMID- 23859558
TI  - Serosurvey and observational study of US Army Veterinary Corps officers for Q
      fever antibodies from 1989 to 2008.
AB  - Since World War II, the military has experienced outbreaks of Q fever among
      deploying units including recent case reports of Q fever in US military personnel
      returning from serving in the Middle East during Operation Iraqi Freedom and
      Operation Enduring Freedom. Occupational exposure and prevalence of Q fever among
      US Army Veterinary Corps officers have not been examined. A retrospective
      serosurvey and observational study of 500 military veterinarians were conducted
      using archived serum specimens from military veterinarians who entered and served
      between 1989 and 2008 and were tested for exposure to Coxiella burnetii.
      Corresponding longitudinal health-related, demographic, medical and deployment
      data were examined. A total of 69 (13.8%) individuals at military entry and 85
      (17%) had late career positive titres. A total of 18 (3.6%) individuals showed
      seroconversion. Women were more likely to be seropositive after military service
      [prevalence ratio (PR) 1.96; 95% confidence interval (CI) 1.15-3.35] and were
      also more likely to seroconvert (incidence rate ratio 3.55; 95% CI 1.19-12.7).
      Women who deployed to Operation Iraqi Freedom were more likely to be seropositive
      (PR 3.17; 95% CI 1.03-9.71). Veterinarians with field service and pathology
      specialties had the highest incidence rates (7.0/1000 PY; 95% CI 4-12 and 3-19,
      respectively). This is the first report documenting US military veterinarians'
      exposure to C. burnetii. Military veterinarians are at risk prior to service,
      with moderate number of new cases developing during service and most maintaining
      titres for long periods of time. Women consistently demonstrated higher
      seroprevalence and incidence levels. As increasing numbers of women enter the
      veterinary profession and subsequently the US Army, this may warrant close
      monitoring. This study likely underestimates exposure and risk and does not
      address chronic health effects, which may be valuable to explore in future health
      studies.

PMID- 23859559
TI  - Differential stress-response expression of two flavonol synthase genes and
      accumulation of flavonols in tartary buckwheat.
AB  - Flavonoids are ubiquitously present in plants and play important roles in these
      organisms as well as in the human diet. Flavonol synthase (FLS) is a key enzyme
      of the flavonoid biosynthetic pathway, acting at the diverging point into the
      flavonol subclass branch. We isolated and characterized a FLS isoform gene,
      FtFLS2, from tartary buckwheat (Fagopyrum tataricum). FtFLS2 shares 48% identity
      and 67% similarity with the previously reported FtFLS1, whereas both genes share
      47-65% identity and 65-69% similarity with FLSs from other plant species. Using
      quantitative real-time PCR and high-performance liquid chromatography (HPLC), the
      expression of FtFLS1/2 and the production of 3 main flavonols (kaempferol,
      myricetin and quercetin) was detected in roots, leaves, stems, flowers and
      different stages of developing seeds. The relationship between the expression of
      the 2 FLS genes and the accumulation of the 3 basic flavonols was analyzed in 2
      tartary buckwheat cultivars. FtFLS1 and FtFLS2 exhibited differential
      transcriptional levels between the tartary buckwheat cultivars 'Hokkai T10' and
      'Hokkai T8'. Generally, higher transcript levels of FtFLS1 and FtFLS2 and a
      higher amount of flavonols were observed in the 'Hokkai T10' cultivar than
      'Hokkai T8'. The content of flavonols showed tissue-specific accumulation between
      the 2 cultivars. The transcription of FtFLS1 was inhibited by the exogenous
      application of abscisic acid (ABA), salicylic acid (SA) and sodium chloride
      (NaCl), while FtFLS2 was not affected by ABA but up-regulated by SA and NaCl.
      These data indicate that the 2 FtFLS isoforms of buckwheat have different
      functions in the response of buckwheat to environmental stress. 

PMID- 23859560
TI  - Alleviation of salt stress in citrus seedlings inoculated with arbuscular
      mycorrhizal fungi depends on the rootstock salt tolerance.
AB  - Seedlings of Cleopatra mandarin (Citrus reshni Hort. ex Tan.) and Alemow (Citrus
      macrophylla Wester) were inoculated with a mixture of AM fungi (Rhizophagus
      irregularis and Funneliformis mosseae) (+AM), or left non-inoculated (-AM). From
      forty-five days after fungal inoculation onwards, half of +AM or -AM plants were
      irrigated with nutrient solution containing 50 mM NaCl. Three months later, AM
      significantly increased plant growth in both Cleopatra mandarin and Alemow
      rootstocks. Plant growth was higher in salinized +AM plants than in non-salinized
      -AM plants, demonstrating that AM compensates the growth limitations imposed by
      salinity. Whereas AM-inoculated Cleopatra mandarin seedlings had a very good
      response under saline treatment, inoculation in Alemow did not alleviate the
      negative effect of salinity. The beneficial effect of mycorrhization is unrelated
      with protection against the uptake of Na or Cl and the effect of AM on these ions
      did not explain the different response of rootstocks. This response was related
      with the nutritional status since our findings confirm that AM fungi can alter
      host responses to salinity stress, improving more the P, K, Fe and Cu plant
      nutrition in Cleopatra mandarin than in Alemow plants. AM inoculation under
      saline treatments also increased root Mg concentration but it was higher in
      Cleopatra mandarin than in Alemow. This could explain why AM fungus did not
      completely recovered chlorophyll concentrations in Alemow and consequently it had
      lower photosynthesis rate than control plants. AM fungi play an essential role in
      citrus rootstock growth and biomass production although the intensity of this
      response depends on the rootstock salinity tolerance.

PMID- 23859557
TI  - Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by
      "molecular tweezers" - from the test tube to animal models.
AB  - Despite decades of research, therapy for diseases caused by abnormal protein
      folding and aggregation (amyloidoses) is limited to treatment of symptoms and
      provides only temporary and moderate relief to sufferers. The failure in
      developing successful disease-modifying drugs for amyloidoses stems from the
      nature of the targets for such drugs - primarily oligomers of amyloidogenic
      proteins, which are distinct from traditional targets, such as enzymes or
      receptors. The oligomers are metastable, do not have well-defined structures, and
      exist in dynamically changing mixtures. Therefore, inhibiting the formation and
      toxicity of these oligomers likely will require out-of-the-box thinking and novel
      strategies. We review here the development of a strategy based on targeting the
      combination of hydrophobic and electrostatic interactions that are key to the
      assembly and toxicity of amyloidogenic proteins using lysine (K)-specific
      "molecular tweezers" (MTs). Our discussion includes a survey of the literature
      demonstrating the important role of K residues in the assembly and toxicity of
      amyloidogenic proteins and the development of a lead MT derivative called CLR01,
      from an inhibitor of protein aggregation in vitro to a drug candidate showing
      effective amelioration of disease symptoms in animal models of Alzheimer's and
      Parkinson's diseases.

PMID- 23859561
TI  - Methionine elicits H2O2 generation and defense gene expression in grapevine and
      reduces Plasmopara viticola infection.
AB  - Methionine (Met) is a nutritionally essential sulfur-containing amino acid (SAA)
      known for its preponderant role as initiator in protein synthesis. However, other
      functions for Met in plants are not well described. The implication of this SAA
      in oxidative stress tolerance has been recently reported, however the mode of
      action of Met is still poorly understood. Here, we analyzed the elicitor activity
      of Met in grapevine as well as its effect on Plasmopara viticola resistance. The
      results show that Met induces hydrogen peroxide (H2O2) generation, a key element
      in plant defense signaling, and upregulates the expression of a battery of
      defense-related genes. Transcript levels of these genes were not further
      modulated by P. viticola inoculation of Met-pretreated plants, suggesting an
      elicitor role rather than a priming role for Met in grapevine. Met treatment also
      reduces P. viticola development in grapevine plants grown under glasshouse
      controlled-conditions. Fungitoxicity assays revealed that Met possesses a
      moderate antifungal activity compared with cysteine (Cys), another SAA known for
      its toxic effect to a large spectrum of fungi. 

PMID- 23859562
TI  - beta-Amino acid and amino-alcohol conjugation of a nonsteroidal anti-inflammatory
      drug (NSAID) imparts hydrogelation displaying remarkable biostability,
      biocompatibility, and anti-inflammatory properties.
AB  - A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np),
      was conjugated with beta-alanine and various combinations of amino alcohols and l
      alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling
      pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH
      7.4). The hydrogels were characterized by rheology and electron microscopy.
      Hydrogelation was probed by FT-IR and temperature-variable (1)H NMR studies.
      Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator
      in the series established a useful structure-property (gelation) correlation. MTT
      assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed
      excellent biocompatibility. The prostaglandin E2 (PGE2) assay of the
      hydrogelators revealed their anti-inflammatory response, which was comparable to
      that of the parent NSAID naproxen sodium (Ns). 

PMID- 23859563
TI  - Kinetics studies of the reactions of main fourth-period monocations (Ga+, Ge+,
      As+, and Se+) with methyl fluoride.
AB  - Thermodynamics and kinetics theoretical studies on the gas-phase reactions of
      fluoromethane with main fourth-period monocations (Ga(+), Ge(+), As(+), and
      Se(+)) have been carried out. Density functional theory (in particular mPW1K
      functional) was employed in the description of the potential energy surfaces, and
      refinement of the energies were done at the CCSD(T) level. The reaction rate
      constants were estimated using variational/conventional microcanonical transition
      state theory. From a thermodynamic viewpoint, the fluorine abstraction product is
      predicted for Ga(+) and Ge(+), whereas for As(+) and Se(+) the elimination
      product, MCH2(+) (M = As, Se) + HF, is the preferred one. Nevertheless, the most
      favorable channel for the reactions of CH3F with Ga(+) and Se(+) cations present
      a net activation barrier. In the case of Ga(+), the reaction proceeds via an
      addition channel forming the adduct complex, CH3FGa(+), whereas for Se(+) no
      reaction is found, in agreement with the experiments. The predicted reaction rate
      constants are in reasonable good agreement with the experimental values
      available. Apart from the harpoon-like mechanism, our results suggest that an
      oxidative addition mechanism seems to play a relevant role. 

PMID- 23859564
TI  - Incorporating psychiatric pharmacogenetics into family practice.

PMID- 23859565
TI  - A massive open online course on pharmacogenomics: not just disruptive innovation
      but a possible solution.

PMID- 23859566
TI  - Pharmacogenetics in neural toxicities of drugs.

PMID- 23859569
TI  - OCT1 genetic variants influence the pharmacokinetics of morphine in children.
AB  - AIM: Large interindividual variability in morphine disposition could contribute
      to unpredictable variability in morphine analgesia and adverse events. Caucasian
      children have more adverse effects and slower morphine clearance than African
      American children. To study variations in intravenous morphine pharmacokinetics
      in children, we examined the influence of genetic polymorphisms in OCT1. METHODS:
      In 146 children undergoing adenotonsillectomy, 146 concentration-time profiles (2
      4 measurements per patient) were available. Population pharmacokinetic analysis
      characterized the profiles in NONMEM((r)) and tested OCT1 variants as covariates.
      RESULTS: Allometrically scaled post hoc Bayesian morphine clearance in
      homozygotes of loss-of-function OCT1 variants (n = 9, OCT1*2-*5/*2-*5) was
      significantly lower (20%) than in wild-type (n = 85, OCT1*1/*1) and heterozygotes
      (n = 52, OCT1*1/*2-*5; p < 0.05). CONCLUSION: Besides bodyweight, OCT1 genotypes
      play a significant role in intravenous morphine pharmacokinetics. Relatively high
      allelic frequencies of defective OCT1 variants among Caucasians may explain their
      lower morphine clearance and possibly higher frequencies of adverse events
      compared with African-American children. Original submitted 21 December 2012;
      Revision submitted 7 May 2013.

PMID- 23859570
TI  - SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic
      drugs: a multicenter cohort study and meta-analysis.
AB  - AIM: Approximately a third of newly diagnosed epilepsy patients do not respond to
      antiepileptic drugs (AEDs). Evidence suggests that low penetrance variants in the
      genes of drug targets such as voltage-gated sodium channels may be involved in
      drug responsiveness. To examine this hypothesis, we compared data from two
      epilepsy cohorts from Malaysia and Hong Kong, as well as a meta-analysis from
      published data. MATERIALS & METHODS: Genotype analysis of 39 polymorphisms
      located in the SCN1A, SCN2A and SCN3A genes was performed on 1504 epilepsy
      patients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was
      performed for pooled data of SCN1A rs3812718 and rs2298771, and SCN2A rs17183814
      polymorphisms. RESULTS: Our data from the Hong Kong and Malaysia cohorts showed
      no significant allele, genotype and haplotype association of polymorphisms in the
      SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. This finding
      was supported by a meta-analysis for SCN1A rs3812718 and rs2298771, and for SCN2A
      rs17183814 polymorphisms. CONCLUSION: Our comprehensive study suggests that
      common polymorphisms in SCN1A, SCN2A and SCN3A do not play major roles in
      influencing response to AEDs. Original submitted 11 March 2013; Revision
      submitted 31 May 2013.

PMID- 23859571
TI  - Impact of pharmacogenetics on CNS side effects related to efavirenz.
AB  - AIM: This article evaluates which genetic factors are involved in CNS toxicity
      related to long-term treatment with efavirenz (EFV) standard doses and their
      relationship with plasma concentrations. PATIENTS & METHODS: A total of 119 HIV
      positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 EFV
      related adverse effects (AEs) were analyzed. RESULTS: Overall, 32.77% of patients
      reported CNS toxicity and 8.40% had concentrations above the therapeutic range. A
      correlation was mainly found between patients with global CNS AEs and high EFV
      maximum steady-state plasma concentration (p = 1.47 * 10(-6)). A preliminary
      analysis confirmed that CYP2B6*6 (516G>T and 785A>G) was the most highly
      correlated (p = 0.005) with AEs and high plasma concentrations. In a second
      analysis adjusting for maximum steady-state plasma concentration, suggestive
      genetic associations were found between BCRP 421C>A, MRP1 816G>A, 5-HT2A 102C>T
      and different AEs. CONCLUSION: The finding of the involvement of these SNPs in
      EFV toxicity opens the door for further studies to confirm their validity and for
      their application in the future clinical practice. Original submitted 18 February
      2013; Revision submitted 17 May 2013.

PMID- 23859572
TI  - Identification of PEAR1 SNPs and their influences on the variation in prasugrel
      pharmacodynamics.
AB  - AIM: The present study aimed to investigate PEAR1 genetic polymorphisms and
      pharmacogenetic variability in the pharmacodynamics of prasugrel, a new oral
      antiplatelet agent, in healthy Han Chinese subjects. PATIENTS & METHODS: The
      inhibition of adenosine diphosphate-induced platelet aggregation was measured pre
      and post-administration using the VerifyNow((r)) P2Y12 assay. The genetic
      sequence of PEAR1 exons and previously reported SNPs in the PEAR1 gene were
      investigated. RESULTS: A total of 28 variations were identified in PEAR1. The
      SNPs in two regions of the PEAR1 gene, from rs3737224 to rs822442, and from
      rs1214331 to rs12566888, probably play important roles in prasugrel
      pharmacodynamics. CONCLUSION: Further studies with larger sample sizes are
      recommended to explore the clinical importance of PEAR1 SNPs in prasugrel and
      other antiplatelet therapies. Original submitted 18 December 2012; Revision
      submitted 26 April 2013.

PMID- 23859573
TI  - CYP1A2 genetic polymorphisms are associated with early antidepressant
      escitalopram metabolism and adverse reactions.
AB  - AIM: The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT)
      to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This
      study tested whether genetic polymorphisms in the CYP1A2 gene are associated with
      the treatment responses to S-CIT. MATERIALS & METHODS: Ten SNPs in CYP1A2 were
      selected and genotyped in 158 patients under S-CIT treatment. The serum levels of
      S-CIT and its metabolites were measured by HPLC. RESULTS: CYP1A2 SNPs rs2069521,
      rs2069526, rs4646425 and rs4646427 are significantly associated with the
      metabolic ratios of S-DDCIT/S-DCIT (p = 0.002, 0.018, 0.008 and 0.004,
      respectively) at week 2 of treatment. Carriers of the allele types associated
      with higher S-DDCIT/S-DCIT ratios had more severe side effects. CONCLUSION: These
      results suggest that genetic variants in CYP1A2 may be indicators for S-CIT
      metabolism and that the fast metabolizers may experience more severe adverse
      reactions in the early stages of S-CIT treatment. Original submitted 27 December
      2012; Revision submitted 15 May 2013.

PMID- 23859574
TI  - Pharmacodynamic genetic variants related to antipsychotic adverse reactions in
      healthy volunteers.
AB  - AIM: Clinical trials with healthy volunteers are a useful model for evaluating
      safety and tolerability, without the interference of concomitant diseases and
      drugs. The present study aims to improve our understanding of antipsychotic
      related adverse reactions (ARs) and their possible association with common
      genetic variants of pharmacodynamic proteins such as neurotransmitter
      receptors/transporters. MATERIALS & METHODS: A total of eight polymorphisms
      located in seven pharmacodynamic-related genes (SCL6A4, MDR1, 5HT2A, DRD2, DRD3,
      COMT and GRIN2B) were genotyped in a cohort of 211 healthy volunteers who
      received a single dose of risperidone (1 mg), olanzapine (5 mg) or quetiapine (25
      mg). RESULTS: Interestingly, a significant association was found between the
      incidence of neurological ARs and specific polymorphisms in key genes (DRD2 and
      SCL6A4). CONCLUSION: Genetic variants in pharmacodynamic genes could represent
      valuable markers of AR risk and antipsychotic safety. Original submitted 7
      February 2013; Revision submitted 3 June 2013.

PMID- 23859575
TI  - Pharmacogenetics of chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a complex genetic disease that
      develops as a result of the interaction of multiple susceptibility genes and
      environmental factors. Major therapeutic approaches include smoking cessation,
      treatment with bronchodilators and corticosteroid therapy. The goal of
      understanding the genetic defects in patients with COPD will be not only to
      redefine the disease phenotypes based on the genetic information, but also to
      alternatively approach patients based on the understanding of COPD pathogenesis,
      which will lead to improved clinical outcomes. Although there is no single ideal
      phenotype for COPD pharmacogenetic studies, thus far, most pharmacogenetics
      studies have focused on the role of variants in the beta2-adrenergic receptor
      gene on bronchodilator response. The inconclusive results yielded by these
      studies highlight many of the difficulties researchers face in assessing the
      influence of genetic variants and in translating this to clinically relevant
      outcomes. 

PMID- 23859576
TI  - Mobilizing pharmacogenomic analyses during clinical trials in drug development.
AB  - The utilization of pharmacogenomics (PGx) in drug development is increasing as
      pharmaceutical companies and regulatory agencies work to understand variation in
      response to medications. The implementation of PGx in clinical trials requires a
      number of considerations that begin early at the point of program development for
      a compound. This article will discuss the issues involved in mobilizing a PGx
      study during the conduct of a clinical trial, including the development of a PGx
      hypothesis, the identification of genetic markers for analysis, PGx platform
      selection and assay development, as well as challenges that arise in relation to
      global laws and regulations related to genetic research and logistical/timeline
      concerns in the execution of a PGx analysis. 

PMID- 23859578
TI  - History and physical examination plus laboratory testing for the diagnosis of
      adult female urinary tract infection.
AB  - BACKGROUND: Emergency physicians often encounter females presenting with symptoms
      suggestive of urinary tract infections (UTIs). The diagnostic accuracy of
      history, physical examination, and bedside laboratory tests for female UTIs in
      emergency departments (EDs) have not been quantitatively described. OBJECTIVES:
      This was a systematic review to determine the utility of history and physical
      examination (H&P) and urinalysis in diagnosing uncomplicated female UTI in the
      ED. METHODS: The medical literature was searched from January 1965 through
      October 2012 in PUBMED and EMBASE using the following criteria: Patients were
      females greater than 18 years of age in the ED suspected of having UTIs.
      Interventions were H&P and urinalysis used to diagnose a UTI. The comparator was
      UTI confirmed by a positive urine culture. The outcome was operating
      characteristics of the interventions in diagnosing a UTI. Study quality was
      assessed using Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS
      2). Sensitivity, specificity, and likelihood ratios (LRs) were calculated using
      Meta-DiSc. RESULTS: Four studies (pooled n = 948) were included with UTI
      prevalence ranging from 40% to 60%. H&P variables all had positive LRs (+LR,
      range = 0.8 to 2.2) and negative LRs (-LR, range = 0.7 to 1.0) that are
      insufficient to significantly alter pretest probability of UTI. Only a positive
      nitrite reaction (+LR = 7.5 to 24.5) was useful to rule in a UTI. To rule out
      UTI, only a negative leukocyte esterase (LE; -LR = 0.2) or blood reaction on
      urine dipstick (-LR = 0.2) were significantly accurate. Increasing pyuria
      directly correlated with +LR, and moderate pyuria (urine white blood cells [uWBC]
      > 50 colony-forming units [CFUs]/ml) and moderate bacteruria were good predictors
      of UTI (+LR = 6.4 and 15.0, respectively). CONCLUSIONS: No single H&P finding can
      accurately rule in or rule out UTI in symptomatic women. Urinalysis with a
      positive nitrite or moderate pyuria and/or bacteruria are accurate predictors of
      a UTI. If the pretest probability of UTI is sufficiently low, a negative
      urinalysis can accurately rule out the diagnosis.

PMID- 23859580
TI  - Stress markers predict mortality in patients with nonspecific complaints
      presenting to the emergency department and may be a useful risk stratification
      tool to support disposition planning.
AB  - OBJECTIVES: To the authors' knowledge, no prospectively validated, biomarker
      based risk stratification tools exist for elderly patients presenting to the
      emergency department (ED) with nonspecific complaints (NSCs), such as generalized
      weakness, despite the fact that an acute serious disease often underlies
      nonspecific disease presentation. The primary purpose for this study was to
      validate the retrospectively derived model for outcome prediction using copeptin
      and peroxiredoxin 4 (Prx4), in a different group of patients, in a prospective
      fashion, in a multicenter setting. The secondary goals were to evaluate the
      potential contribution of the midregional portion of the precursor of
      adrenomedullin (MR-proADM) for outcome prediction and to investigate whether
      disposition decisions show promise for potential improvement by using biomarker
      levels in addition to a clinical assessment. METHODS: The Basel Nonspecific
      Complaints (BANC) study is a delayed-type cross-sectional diagnostic study,
      carried out in three EDs in Switzerland, with a prospective 30-day follow-up.
      Patients presenting to the ED with NSCs, as defined previously, were included if
      their vital signs were within predefined limits. Measurement of biomarkers was
      performed in serum samples with sandwich immunoluminometric assays. To examine
      the disposition process, the final disposition was compared with a combination of
      the first clinical disposition decision and the risk assessment, which included
      the biomarker MR-proADM in a retrospective simulation. Patients were divided into
      three groups according to MR-proADM concentration, defining three risk classes
      with three disposition possibilities (admission to tertiary care, transfer to
      geriatric hospital, discharge). RESULTS: Thirty-three 30-day nonsurvivors were
      observed from among 504 study patients with NSCs. Biomarker levels were
      significantly greater in nonsurvivors than survivors (p < 0.0001 for all three
      biomarkers). Univariate Cox models reveal a C-index of 0.732 for MR-proADM, 0.719
      for Prx4, and 0.723 for copeptin. The incremental added value for chi-square
      obtained via multivariate modeling showed that models inclusive of MR-proADM,
      copeptin, or Prx4 are superior to and independent of models limited to sex and
      age. The incrementally added chi-square for MR-proADM, beyond the chi-square of a
      base model consisting of age and sex, was 29.79 (p < 0.00001). In a multimarker
      approach, only Prx4 provided additional information to MR-proADM alone (C-index =
      0.77). Applying an algorithm combining physicians' first clinical assessment plus
      biomarker information to derive a modified risk assessment, reassignment would
      lead to a potential decrease of 48 admissions to acute care, seven additional
      transfers to geriatric care, and 41 additional discharges (negative likelihood
      ratio [-LR] = 0.13). Analysis of 30-day mortality reveals that our algorithm is
      not inferior in terms of safety. CONCLUSIONS: In this study the authors confirm
      that these new stress biomarkers permit reliable prognostication of adverse
      outcomes in a heterogeneous group of patients with NSCs. A simulation showed that
      this prognostic information could be useful to enhance the appropriateness of
      disposition decisions of ED patients with NSC. The use of biomarkers for risk
      stratification in this patient group should be evaluated with prospective
      intervention studies.

PMID- 23859579
TI  - Mechanical ventilation and acute lung injury in emergency department patients
      with severe sepsis and septic shock: an observational study.
AB  - OBJECTIVES: The objectives were to characterize the use of mechanical ventilation
      in the emergency department (ED), with respect to ventilator settings,
      monitoring, and titration and to determine the incidence of progression to acute
      lung injury (ALI) after admission, examining the influence of factors present in
      the ED on ALI progression. METHODS: This was a retrospective, observational
      cohort study of mechanically ventilated patients with severe sepsis and septic
      shock (June 2005 to May 2010), presenting to an academic ED with an annual census
      of >95,000 patients. All patients in the study (n = 251) were analyzed for
      characterization of mechanical ventilation use in the ED. The primary outcome
      variable of interest was the incidence of ALI progression after intensive care
      unit (ICU) admission from the ED and risk factors present in the ED associated
      with this outcome. Secondary analyses included ALI present in the ED and clinical
      outcomes comparing all patients progressing to ALI versus no ALI. To assess
      predictors of progression to ALI, significant variables in univariable analyses
      at a p <= 0.10 level were candidates for inclusion in a bidirectional, stepwise,
      multivariable logistic regression analysis. RESULTS: Lung-protective ventilation
      was used in 68 patients (27.1%) and did not differ based on ALI status. Delivered
      tidal volume was highly variable, with a median tidal volume delivered of 8.8
      mL/kg ideal body weight (IBW; interquartile range [IQR] = 7.8 to 10.0) and a
      range of 5.2 to 14.6 mL/kg IBW. Sixty-nine patients (27.5%) in the entire cohort
      progressed to ALI after admission to the hospital, with a mean (+/-SD) onset of
      2.1 (+/-1) days. Multivariable logistic regression analysis demonstrated that a
      higher body mass index (BMI), higher Sequential Organ Failure Assessment (SOFA)
      score, and ED vasopressor use were associated with progression to ALI. There was
      no association between ED ventilator settings and progression to ALI. Compared to
      patients who did not progress to ALI, patients progressing to ALI after admission
      from the ED had an increase in mechanical ventilator duration, vasopressor
      dependence, and hospital length of stay (LOS). CONCLUSIONS: Lung-protective
      ventilation is uncommon in the ED, regardless of ALI status. Given the frequency
      of ALI in the ED, the progression shortly after ICU admission, and the clinical
      consequences of this syndrome, the effect of ED-based interventions aimed at
      reducing the sequelae of ALI should be investigated further.

PMID- 23859581
TI  - Sex preferences in cardiovascular testing: the contribution of the patient
      physician discussion.
AB  - OBJECTIVES: Prior studies suggest that a decreased cardiac catheterization rate
      for women with acute coronary syndrome (ACS) is partially attributed to gender
      differences in patient preferences for testing. The hypothesis was that these
      preferences are influenced by physician recommendations for cardiovascular
      testing. METHODS: This was a cohort study of patients who presented to an
      emergency department (ED) with chest pain. At the time of ED disposition,
      patients were surveyed to assess whether or not the doctor discussed the
      possibility of coronary artery disease (CAD), the physician's recommendations for
      diagnostic testing, and the patient's preferences for further testing. The survey
      was repeated at the time of discharge from the hospital if the patient was
      admitted and again at 30 days for all patients. The main outcome was patient
      reported physician recommendation for testing, and the secondary outcome was
      patient preference for cardiovascular testing. RESULTS: There were 206 patients
      enrolled (118 women, 88 men). Women were less likely than men to receive cardiac
      catheterization as inpatients (9.8% vs. 20.0%, p = 0.04). In the ED, women were
      less likely to be recommended for stress testing (8.5% vs. 19.3%, p = 0.02) or
      cardiac catheterization (4.2% vs. 13.6%, p = 0.02) or to see a cardiologist (8.5%
      vs. 22.7%, p < 0.01). As inpatients, women were more likely to be told that no
      further testing was needed (70.5% vs. 50.0%, p = 0.03). While there was higher
      incidence of prior CAD and myocardial infarction among the men in the study,
      analysis after removal of these patients did not alter results. Physicians were
      less likely to counsel women about diagnostic testing options in the ED (10.1%
      vs. 22.7%, p = 0.03), as inpatients (11.5% vs. 40.0%, p < 0.01), and as
      outpatients (26.1% vs. 48.6%, p = 0.04). No patients in the study refused their
      doctors' recommendations. Women were less likely to prefer catheterization in the
      ED (5.1% vs. 15.9%, p = 0.01) and were more likely to prefer no further testing
      as inpatients (60.7% vs. 40.0%, p = 0.02). CONCLUSIONS: Women who presented to
      the ED with symptoms concerning for ACS reported lower rates of physician
      recommendation for cardiovascular testing, as well as lower rates of counseling
      regarding cardiac etiologies of their chest pain. These findings suggest sex
      differences in preference for cardiovascular testing may be partially explained
      by the discussions between women and their doctors.

PMID- 23859582
TI  - Rising annual costs of dizziness presentations to U.S. emergency departments.
AB  - OBJECTIVES: Dizziness and vertigo account for roughly 4% of chief symptoms in the
      emergency department (ED). Little is known about the aggregate costs of ED
      evaluations for these patients. The authors sought to estimate the annual
      national costs associated with ED visits for dizziness. METHODS: This cost study
      of adult U.S. ED visits presenting with dizziness or vertigo combined public-use
      ED visit data (1995 to 2009) from the National Hospital Ambulatory Medical Care
      Survey (NHAMCS) and cost data (2003 to 2008) from the Medical Expenditure Panel
      Survey (MEPS). We calculated total visits, test utilization, and ED diagnoses
      from NHAMCS. Diagnosis groups were defined using the Healthcare Cost and
      Utilization Project's Clinical Classifications Software (HCUP-CCS). Total visits
      and the proportion undergoing neuroimaging for future years were extrapolated
      using an autoregressive forecasting model. The average ED visit cost-per
      diagnosis-group from MEPS were calculated, adjusting to 2011 dollars using the
      Hospital Personal Health Care Expenditures price index. An overall weighted mean
      across the diagnostic groups was used to estimate total national costs. Year 2011
      data are reported in 2011 dollars. RESULTS: The estimated number of 2011 US ED
      visits for dizziness or vertigo was 3.9 million (95% confidence interval [CI] =
      3.6 to 4.2 million). The proportion undergoing diagnostic imaging by computed
      tomography (CT), magnetic resonance imaging (MRI), or both in 2011 was estimated
      to be 39.9% (39.4% CT, 2.3% MRI). The mean per-ED-dizziness-visit cost was $1,004
      in 2011 dollars. The total extrapolated 2011 national costs were $3.9 billion.
      HCUP-CCS key diagnostic groups for those presenting with dizziness and vertigo
      included the following (fraction of dizziness visits, cost-per-ED-visit,
      attributable annual national costs): otologic/vestibular (25.7%; $768; $757
      million), cardiovascular (16.5%, $1,489; $941 million), and cerebrovascular
      (3.1%; $1059; $127 million). Neuroimaging was estimated to account for about 12%
      of the total costs for dizziness visits in 2011 (CT scans $360 million, MRI scans
      $110 million). CONCLUSIONS: Total U.S. national costs for patients presenting
      with dizziness to the ED are substantial and are estimated to now exceed $4
      billion per year (about 4% of total ED costs). Rising costs over time appear to
      reflect the rising prevalence of ED visits for dizziness and increased rates of
      imaging use. Future economic studies should focus on the specific breakdown of
      total costs, emphasizing areas of high cost and use that might be safely reduced.

PMID- 23859583
TI  - Performance of ultrasound in the diagnosis of appendicitis in children in a
      multicenter cohort.
AB  - OBJECTIVES: The objectives were to assess the test characteristics of ultrasound
      (US) in diagnosing appendicitis in children and to evaluate site-related
      variations based on the frequency of its use. Additionally, the authors assessed
      the test characteristics of US when the appendix was clearly visualized. METHODS:
      This was a secondary analysis of a prospective, 10-center observational study.
      Children aged 3 to 18 years with acute abdominal pain concerning for appendicitis
      were enrolled. US was performed at the discretion of the treating physician.
      RESULTS: Of 2,625 patients enrolled, 965 (36.8%) underwent abdominal US. US had
      an overall sensitivity of 72.5% (95% confidence interval [CI] = 58.8% to 86.3%)
      and specificity 97.0% (95% CI = 96.2% to 97.9%) in diagnosing appendicitis. US
      sensitivity was 77.7% at the three sites (combined) that used it in 90% of cases,
      51.6% at a site that used it in 50% of cases, and 35% at the four remaining sites
      (combined) that used it in 9% of cases. US retained a high specificity of 96% to
      99% at all sites. Of the 469 (48.6%) cases across sites where the appendix was
      clearly visualized on US, its sensitivity was 97.9% (95% CI = 95.2% to 99.9%),
      with a specificity of 91.7% (95% CI = 86.7% to 96.7%). CONCLUSIONS: Ultrasound
      sensitivity and the rate of visualization of the appendix on US varied across
      sites and appeared to improve with more frequent use. US had universally high
      sensitivity and specificity when the appendix was clearly identified. Other
      diagnostic modalities should be considered when the appendix is not definitively
      visualized by US.

PMID- 23859584
TI  - Evaluation of the diagnostic accuracy of plasma markers for early diagnosis in
      patients suspected for acute appendicitis.
AB  - OBJECTIVES: The main objective of this study was to evaluate the diagnostic
      accuracy of two novel biomarkers, calprotectin (CP) and serum amyloid A (SAA),
      along with the more traditional inflammatory markers C-reactive protein (CRP) and
      white blood cell count (WBC), in patients suspected of having acute appendicitis
      (AA). The secondary objective was to compare diagnostic accuracy of these
      biomarkers with a clinical scoring system and radiologic imaging. METHODS: A
      total of 233 patients with suspected AA, presenting to the emergency department
      (ED) between January 2010 and September 2010, and 52 healthy individuals serving
      as controls, were included in the study. Blood was drawn and CP and SAA-1
      concentrations were measured using enzyme-linked immunosorbent assay (ELISA). CRP
      and WBC concentrations were routinely measured and retrospectively abstracted
      from the electronic health record, together with physical examination findings
      and radiologic reports. The Alvarado score was calculated as a clinical scoring
      system for AA. Final diagnosis of AA was based on histopathologic examination.
      The Mann-Whitney U-test was used for between-group comparisons. Receiver
      operating characteristic (ROC) curves were used to measure the diagnostic
      accuracy for the tests and to determine the best cutoff points. RESULTS: Seventy
      seven of 233 patients (33%) had proven AA. Median plasma levels for CP and SAA-1
      were significantly higher in patients with AA than in those with another final
      diagnosis (CP, 320.9 ng/mL vs. 212.9 ng/mL; SAA-1, 30 mg/mL vs. 0.6 mg/mL; p <
      0.001). CRP and WBC were significantly higher in patients with AA as well. The
      Alvarado score was helpful at the extremes (<3 or >7). Ultrasound (US) had a
      sensitivity of 84% and a specificity of 94%. Computed tomography (CT) had a
      sensitivity of 100% and a specificity of 91%. The area under the ROC (95%
      confidence interval [CI]) was 0.67 (95% CI = 0.60 to 0.74) for CP, 0.76 (95% CI =
      0.70 to 0.82) for SAA, 0.71 (95% CI = 0.64 to 0.78) for CRP, and 0.79 (95% CI =
      0.73 to 0.85) for WBC. No cutoff points had high enough sensitivity and
      specificity to accurately diagnose AA. However, a high sensitivity of 97% was
      shown at 7.5 * 10(9) /L for WBC and 0.375 mg/mL for SAA. CONCLUSIONS: CP, SAA-1,
      CRP, and WBC were significantly elevated in patients with AA. None had cutoff
      points that could accurately discriminate between AA and other pathology in
      patients with suspected AA. A WBC < 7.5 * 10(9) /L, with a low level of clinical
      suspicion for AA, can identify a subgroup of patients who may be sent home
      without further evaluation, but who should have available next-day follow-up.

PMID- 23859585
TI  - Emergency physicians accurately interpret video capsule endoscopy findings in
      suspected upper gastrointestinal hemorrhage: a video survey.
AB  - BACKGROUND: Acute upper gastrointestinal (GI) hemorrhage is a common emergency
      department (ED) presentation whose severity ranges from benign to life
      threatening and the best tool to risk stratify the disease is an upper endoscopy,
      either by scope or by capsule, a procedure performed almost exclusively by
      gastroenterologists. Unfortunately, on-call gastroenterology specialists are
      often unavailable, and emergency physicians (EPs) currently lack an alternative
      method to endoscopically visualize a suspected acute upper GI hemorrhage. Recent
      reports have shown that video capsule endoscopy is well tolerated by ED patients
      and has similar sensitivity and specificity to endoscopy for upper GI hemorrhage.
      OBJECTIVES: The study objective was to determine if EPs can detect upper GI
      bleeding on capsule endoscopy after a brief training session. METHODS: A survey
      study was designed to demonstrate video examples of capsule endoscopy to EPs and
      determine if they could detect upper GI bleeding after a brief training session.
      All videos were generated from a prior ED-based study on patients with suspected
      acute upper GI hemorrhage. The training session consisted of less than 10 minutes
      of background information and capsule endoscopy video examples. EPs were
      recruited at the American College of Emergency Physicians Scientific Assembly in
      Denver, Colorado, from October 8, 2012, to October 10, 2012. Inclusion criteria
      included being an ED resident or attending physician and the exclusion criteria
      included any formal endoscopy training. The authors analyzed the agreement
      between the EPs and expert adjudicated capsule endoscopy readings for each
      capsule endoscopy video. For the outcome categories of blood (fresh or coffee
      grounds type) or no blood detected, the sensitivity and specificity were
      calculated. RESULTS: A total of 126 EPs were enrolled. Compared to expert
      gastroenterology-adjudicated interpretation, the sensitivity to detect blood was
      0.94 (95% confidence interval [CI] = 0.91 to 0.96) and specificity was 0.87 (95%
      CI = 0.80 to 0.92). CONCLUSIONS: After brief training, EPs can accurately
      interpret video capsule endoscopy findings of presence of gross blood or no blood
      with high sensitivity and specificity.

PMID- 23859586
TI  - An ethical framework for the management of pain in the emergency department.
AB  - Pain is a ubiquitous problem, affecting more than 100 million individuals in the
      United States chronically and many more in the acute setting. Up to three
      quarters of patients presenting to the emergency department (ED) report pain as a
      key component of their reasons for requiring acute care. While pain management is
      a fundamental component of emergency medicine (EM), there are numerous
      attitudinal and structural barriers that have been identified to effectively
      providing pain control in the ED. Coupled with public demands and administrative
      mandates, concerns surrounding ED pain management have reached a crisis level
      that should be considered an ethical issue in the profession of EM. In this
      article, the authors propose an ethical framework based on a combination of
      virtue, narrative, and relationship theories that can be used to address the
      clinical dilemmas that arise in managing pain in ED patients. 

PMID- 23859587
TI  - The emergency medicine milestones: a validation study.
AB  - OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) and
      the American Board of Medical Specialties sought to define milestones for skill
      and knowledge acquisition during residency training. Milestones are significant
      objective observable events. The milestones are listed within a structure that is
      derived from the ACGME general competencies. Major groups of milestones are
      called "subcompetencies." The original 24 subcompetencies containing 255
      milestones for emergency medicine (EM) were developed through a
      multiorganizational group representing most EM stakeholder groups. To assure that
      the milestones reflected EM resident progress throughout training, the EM
      Milestones Working Group (EM MWG) sought to validate the individual milestones.
      METHODS: A computer-based survey was sent to all EM residency programs. The
      survey period began on April 30, 2012, and concluded on May 15, 2012. Respondents
      were asked to assign each milestone to a specific level of skill or knowledge
      acquisition. These levels ranged from a beginning resident to an accomplished
      clinician. There were two different forms that divided the milestones into two
      groups of 12 subcompetencies each. Surveys were randomly assigned to programs.
      RESULTS: There were five respondents (the program director and four key faculty)
      requested from each of the 159 residences. There were responses from 96 programs
      (60.4%). Of the 795 survey recipients, 28 were excluded due to prior exposure to
      the EM milestones. Of the remaining 767 potential respondents, 281 completed the
      survey (36.6%) within a 16-day period. Based on the survey results, the working
      group adjusted the milestones in the following ways: one entire subcompetency
      (teaching) was eliminated, six new milestones were created, 34 milestones were
      eliminated, 26 milestones were reassigned to a lower level score, and 20 were
      reassigned to a higher level. Nineteen milestones were edited to provide greater
      clarity. The final result was 227 discrete milestones among 23 subcompetencies.
      CONCLUSIONS: The EM milestones were validated through a milestone assignment
      process using a computer-based survey completed by program directors and key
      faculty. Milestones were revised in accordance with the results to better align
      assignment within each performance level.

PMID- 23859588
TI  - How competent are emergency medicine interns for level 1 milestones: who is
      responsible?
AB  - OBJECTIVES: The Next Accreditation System (NAS) of the Accreditation Council for
      Graduate Medical Education (ACGME) includes the implementation of developmental
      milestones for each specialty. The milestones include five progressively
      advancing skill levels, with Level 1 defining the skill level of a medical
      student graduate, and Level 5, that of an attending physician. The goal of this
      study was to query interns on how well they thought their medical school had
      prepared them to meet the proposed emergency medicine (EM) Level 1 milestones.
      METHODS: In July 2012, an electronic survey was distributed to the interns of 13
      EM residency programs, asking interns whether they were taught and assessed on
      the proposed Level 1 milestones. RESULTS: Of possible participants, 113 of 161
      interns responded (70% response rate). The interns represented all four regions
      of the country. The interns responded that the rates of Level 1 milestones they
      had been taught ranged from 61% for ultrasound to 98% for performance of focused
      history and physical examination. A substantial number of interns (up to 39%)
      reported no instruction on milestones such as patient disposition, pain
      management, and vascular access. Graduating medical students were less commonly
      assessed than taught the milestones. Skills with technology, including "explain
      the role of the electronic health record and computerized physician order entry,"
      were assessed for only 39% of interns, and knowledge (USMLE) and history and
      physical were assessed in nearly all interns. Disposition, ultrasound,
      multitasking, and wound management were assessed less than half of the time.
      CONCLUSIONS: Many entering EM interns may not have had either teaching or
      assessment on the knowledge, skills, and behaviors making up the Level 1
      milestones expected for graduating medical students. Thus, there is a potential
      gap in the teaching and assessment of EM interns. Based on these findings, it is
      unclear who will be responsible (medical schools, EM clerkships, or residency
      programs) for ensuring that medical students entering residency have achieved
      Level 1 milestones.

PMID- 23859589
TI  - CORD-AEUS: consensus document for the emergency ultrasound milestone project.
AB  - In 2012, the Accreditation Council for Graduate Medical Education (ACGME)
      designated ultrasound (US) as one of 23 milestone competencies for emergency
      medicine (EM) residency graduates. With increasing scrutiny of medical
      educational programs and their effect on patient safety and health care delivery,
      it is imperative to ensure that US training and competency assessment is
      standardized. In 2011, a multiorganizational committee composed of
      representatives from the Council of Emergency Medicine Residency Directors
      (CORD), the Academy of Emergency Ultrasound of the Society for Academic Emergency
      Medicine (SAEM), the Ultrasound Section of the American College of Emergency
      Physicians (ACEM), and the Emergency Medicine Residents' Association was formed
      to suggest standards for resident emergency ultrasound (EUS) competency
      assessment and to write a document that addresses the ACGME milestones. This
      article contains a historical perspective on resident training in EUS and a table
      of core skills deemed to be a minimum standard for the graduating EM resident. A
      survey summary of focused EUS education in EM residencies is described, as well
      as a suggestion for structuring education in residency. Finally, adjuncts to a
      quantitative measurement of resident competency for EUS are offered. 

PMID- 23859590
TI  - Amyotrophic lateral sclerosis and Huntington's disease: neurodegenerative link or
      coincidence?

PMID- 23859591
TI  - Metallic-like stoichiometric copper sulfide nanocrystals: phase- and shape
      selective synthesis, near-infrared surface plasmon resonance properties, and
      their modeling.
AB  - In the realm of semiconductor nanomaterials, a crystal lattice heavily doped with
      cation/anion vacancies or ionized atomic impurities is considered to be a general
      prerequisite to accommodating excess free carriers that can support localized
      surface plasmon resonance (LSPR). Here, we demonstrate a surfactant-assisted
      nonaqueous route to anisotropic copper sulfide nanocrystals, selectively trapped
      in the covellite phase, which can exhibit intense, size-tunable LSPR at near
      infrared wavelengths despite their stoichiometric, undoped structure.
      Experimental extinction spectra are satisfactorily reproduced by theoretical
      calculations performed by the discrete dipole approximation method within the
      framework of the Drude-Sommerfeld model. The LSPR response of the nanocrystals
      and its geometry dependence are interpreted as arising from the inherent metallic
      like character of covellite, allowed by a significant density of lattice
      constitutional valence-band free holes. As a consequence of the unique electronic
      properties of the nanocrystals and of their monodispersity, coherent excitation
      of symmetric radial breathing modes is observed for the first time in transient
      absorption experiments at LSPR wavelengths. 

PMID- 23859592
TI  - Novel dedicator of cytokinesis 8 mutations identified by multiplex ligation
      dependent probe amplification.
AB  - Dedicator of cytokinesis 8 (DOCK8) deficiency is an innate error of adaptive
      immunity characterized by recurrent infections with viruses, bacteria and fungi,
      very high serum IgE concentrations, and a progressive deterioration of T- and B
      cell-mediated immunity. We studied the genetic and immunological features of two
      sisters (aged 11 and 6 yr). Mutational analysis of genomic DNA and cDNA from the
      patients and their parents, by a combination of PCR and bidirectional targeted
      sequencing, failed to localize the mutation site. However, a multiplex ligation
      dependent probe amplification (MLPA) assay revealed two novel large deletions,
      del1-14 exons and del8-18 exons, of DOCK8 in both patients. Immunoblot analysis
      demonstrated that DOCK8 protein was absent from the peripheral blood lymphocytes
      of both patients. These data suggest that compound heterozygous del1-14 exons and
      del8-18 exons mutations result in a loss of function of DOCK8 protein and a
      typical DOCK8 deficiency phenotype.

PMID- 23859593
TI  - Synthetic ePTFE grafts coated with an anti-CD133 antibody-functionalized
      heparin/collagen multilayer with rapid in vivo endothelialization properties.
AB  - An anti-CD133 antibody multilayer functionalized by heparin/collagen on an
      expanded polytetrafluoroethylene (ePTFE) graft was developed to accelerate early
      endothelialization. The surface modification of ePTFE grafts demonstrated that
      the multilayer is stable in static incubation and shaking conditions and that the
      anti-CD133 antibodies were successfully cross-linked onto the surface. Blood
      compatibility tests revealed that the coimmobilized heparin/collagen films in the
      presence or absence of anti-CD133 antibodies prolonged the blood coagulation time
      and that there was less platelet activation and aggregation, whereas the
      hemolysis rate was comparable with the bare ePTFE grafts. Cellular proliferation
      was not inhibited, as the heparin/collagen synthetic vascular grafts coated with
      CD133 antibody showed little cytotoxicity. The endothelial cells adhered well to
      the modified ePTFE grafts during a cell adhesion assay. A porcine carotid artery
      transplantation model was used to evaluate the modified ePTFE grafts in vivo. The
      results of histopathological staining and scanning electron microscopy indicated
      that the anti-CD133 antibody was able to accelerate the attachment of vascular
      endothelial cells onto the ePTFE grafts, resulting in early rapid
      endothelialization. The success of the anti-CD133 antibody-functionalized
      heparin/collagen multilayer will provide an effective selection system for the
      surface modification of synthetic vascular grafts and improve their use in
      clinical applications. 

PMID- 23859594
TI  - Alterations in frontostriatal pathways in children born very preterm.
AB  - AIM: Children born very preterm (<32wks' gestation) are at risk of white matter
      injury, particularly in frontostriatal pathways that mediate executive
      functioning. However, it is unclear whether very preterm children without
      evidence of neonatal brain injury manifest long-term white matter microstructural
      differences once they reach school age and if this is related to cognitive
      impairments. METHOD: Twenty school-aged children born very preterm (11 males,
      nine females; mean age 8y 6mo, standard error [SE] 1.68mo, range 7y 7mo-9y 6mo;
      gestational age range 24-30wks, mean gestational age 26.9wks, SE 0.4wk;
      birthweight 988 g, SE 46 g, range 570-1424 g) without evidence of neonatal brain
      injury, and 20 sex- and age-matched term-born children (mean age 8y 4.8mo, SE
      1.92mo; range 7y 2mo-9y-10.8mo) underwent neurodevelopmental assessment and
      diffusion tensor imaging. RESULTS: Fractional anisotropy, mean diffusivity, axial
      diffusivity, and radial diffusivity were calculated within all white matter
      pathways and within frontostriatal projections. Children born preterm had
      decreased fractional anisotropy in the territories of the left external capsule,
      superior longitudinal fasciculus, uncinate fasciculus, and inferior fronto
      occipital fasciculus. Measures of intelligence were negatively correlated with
      frontostriatal fractional anisotropy only in males born preterm. INTERPRETATION:
      Results indicate that very preterm-born children exhibit white matter
      disturbances that persist into middle childhood, with potential sex differences
      in the association between these white matter alterations and cognitive function.

PMID- 23859596
TI  - Depolarization-induced suppression of a glycinergic synapse in the superior
      olivary complex by endocannabinoids.
AB  - The neuronal endocannabinoid system is known to depress synaptic inputs
      retrogradely in an activity-dependent manner. This mechanism has been generally
      described for excitatory glutamatergic and inhibitory GABAergic synapses. Here,
      we report that neurones in the auditory brainstem of the Mongolian gerbil
      (Meriones unguiculatus) retrogradely regulate the strength of their inputs via
      the endocannabinoid system. By means of whole-cell patch-clamp recordings, we
      found that retrograde endocannabinoid signalling attenuates both glycinergic and
      glutamatergic post-synaptic currents in the same types of neurones. Accordingly,
      we detected the cannabinoid receptor 1 in excitatory and inhibitory pre-synapses
      as well as the endocannabinoid-synthesising enzymes (diacylglycerol lipase
      alpha/beta, DAGLalpha/beta) post-synaptically through immunohistochemical
      stainings. Our study was performed with animals aged 10-15 days, that is, in the
      time window around the onset of hearing. Therefore, we suggest that retrograde
      endocannabinoid signalling has a role in adapting inputs during the functionally
      important switch from spontaneously generated to sound-related signals.

PMID- 23859597
TI  - Equine glaucoma: a histopathologic retrospective study (1999-2012).
AB  - PURPOSE: To characterize and describe the histopathologic findings in equine
      globes enucleated due to glaucoma. METHODS: Medical records at The Ohio State
      University from 1999 to 2012 were reviewed retrospectively. Signalment, history,
      and treatment data were collected, and histologic slides of enucleated globes
      were examined and lesions recorded. Twenty-three eyes from 23 horses were
      eligible for inclusion in this study. RESULTS: The majority of affected horses
      were > 15 years of age (65%). The ages ranged from 5 to 35 years (mean = 17.4
      years). The left eye was affected in 10 cases (43%) and the right eye in 13 cases
      (57%). There were 13 mares (56%) and 10 geldings (44%). Quarter Horses (30%),
      Appaloosas (26%), and Thoroughbreds (22%) were the most common breeds in the
      study population. The most common histopathologic changes included
      hypercellularity of the optic nerve (93%), retinal atrophy (89%), corneal
      vascularization (83%), descemetization of pectinate ligaments (83%),
      hypercellularity of the anterior corneal stroma (75%), posterior bowing of the
      iris base (74%), ciliary body atrophy (74%), corneal striae (70%), pars plana
      elongation (60%), cataract (53%), and collapsed ciliary cleft/trabecular meshwork
      (52%). Evidence of uveitis (cataract, lymphoplasmacytic infiltration of the uvea,
      and/or anterior or posterior synechiae) was present in 20/23 eyes (87%).
      CONCLUSIONS: Equine glaucoma most commonly occurs secondary to uveitis with
      Appaloosas and older horses predisposed. Histologic changes are comparable to
      prior reports of chronic glaucoma; notable findings not previously described in
      the horse were posterior bowing of the iris base and relative sparing of the
      superior retina from atrophy associated with elevated IOP.

PMID- 23859595
TI  - Ecological speciation in anemone-associated snapping shrimps (Alpheus armatus
      species complex).
AB  - Divergent natural selection driven by competition for limited resources can
      promote speciation, even in the presence of gene flow. Reproductive isolation is
      more likely to result from divergent selection when the partitioned resource is
      closely linked to mating. Obligate symbiosis and host fidelity (mating on or near
      the host) can provide this link, creating ideal conditions for speciation in the
      absence of physical barriers to dispersal. Symbiotic organisms often experience
      competition for hosts, and host fidelity ensures that divergent selection for a
      specific host or host habitat can lead to speciation and strengthen pre-existing
      reproductive barriers. Here, we present evidence that diversification of a
      sympatric species complex occurred despite the potential for gene flow and that
      partitioning of host resources (both by species and by host habitat) has
      contributed to this diversification. Four species of snapping shrimps (Alpheus
      armatus, A. immaculatus, A. polystictus and A. roquensis) are distributed mainly
      sympatrically in the Caribbean, while the fifth species (A. rudolphi) is
      restricted to Brazil. All five species are obligate commensals of sea anemones
      with a high degree of fidelity and ecological specificity for host species and
      habitat. We analysed sequence data from 10 nuclear genes and the mitochondrial
      COI gene in 11-16 individuals from each of the Caribbean taxa and from the only
      available specimen of the Brazilian taxon. Phylogenetic analyses support
      morphology-based species assignments and a well-supported Caribbean clade. The
      Brazilian A. rudolphi is recovered as an outgroup to the Caribbean taxa.
      Isolation-migration coalescent analysis provides evidence for historical gene
      flow among sympatric sister species. Our data suggest that both selection for a
      novel host and selection for host microhabitat may have promoted diversification
      of this complex despite gene flow. 

PMID- 23859599
TI  - Slow aromatic ring flips detected despite near-degenerate NMR frequencies of the
      exchanging nuclei.
AB  - Aromatic ring flips of Phe and Tyr residues are a hallmark of protein dynamics
      with a long history in molecular biophysics. Ring flips lead to symmetric
      exchange of nuclei between sites with distinct magnetic environments, which can
      be probed by NMR spectroscopy. Current knowledge of ring-flip rates originates
      from rare cases in which the chemical shift difference between the two sites is
      sufficiently large and the ring-flip rate sufficiently slow, typically kflip <
      10(3) s(-1), so that separate peaks are observed in the NMR spectrum for the two
      nuclei, enabling direct measurement of the flip rate. By contrast, a great
      majority of aromatic rings show single peaks for each of the pairs of delta or
      epsilon nuclei, which commonly are taken as inferential evidence that the flip
      rate is fast, kflip < 10(3) s(-1), even though rate measurements have not been
      achieved. Here we report a novel approach that makes it possible to identify slow
      ring flips in previously inaccessible cases where only single peaks are observed.
      We demonstrate that Y21 in the bovine pancreatic trypsin inhibitor (BPTI) has a
      slow ring-flip rate, kflip < 100 s(-1), a result that contrasts with previous
      estimates of 10(4)-10(6) s(-1) inferred from the single-peak spectrum of Y21.
      Comparison with a recent 1 ms molecular dynamics trajectory of BPTI shows
      qualitative agreement and highlights the value of accurate aromatic ring flip
      data as an important benchmark for molecular dynamics simulations of proteins
      across wide time scales.

PMID- 23859598
TI  - Deficiency of GRP94 in the hematopoietic system alters proliferation regulators
      in hematopoietic stem cells.
AB  - We have previously reported that acute inducible knockout of the endoplasmic
      reticulum chaperone GRP94 led to an expansion of the hematopoietic stem and
      progenitor cell pool. Here, we investigated the effectors and mechanisms for this
      phenomenon. We observed an increase in AKT activation in freshly isolated GRP94
      null HSC-enriched Lin(-) Sca-1(+) c-Kit(+) (LSK) cells, corresponding with higher
      production of PI(3,4,5)P3, indicative of PI3K activation. Treatment of GRP94-null
      LSK cells with the AKT inhibitor MK2206 compromised cell expansion, suggesting a
      causal relationship between elevated AKT activation and increased proliferation
      in GRP94-null HSCs. Microarray analysis demonstrated a 97% reduction in the
      expression of the hematopoietic cell cycle regulator Ms4a3 in the GRP94-null LSK
      cells, and real-time quantitative PCR confirmed this down-regulation in the LSK
      cells but not in the total bone marrow (BM). A further examination comparing
      freshly isolated BM LSK cells with spleen LSK cells, as well as BM LSK cells
      cultured in vitro, revealed specific down-regulation of Ms4a3 in freshly isolated
      BM GRP94-null LSK cells. On examining cell surface proteins that are known to
      regulate stem cell proliferation, we observed a reduced expression of cell
      surface connexin 32 (Cx32) plaques in GRP94-null LSK cells. However, suppression
      of Cx32 hemichannel activity in wild-type LSK cells through mimetic peptides did
      not lead to increased LSK cell proliferation in vitro. Two other important cell
      surface proteins that mediate HSC-niche interactions, specifically Tie2 and
      CXCR4, were not impaired by Grp94 deletion. Collectively, our study uncovers
      novel and unique roles of GRP94 in regulating HSC proliferation. 

PMID- 23859600
TI  - Determination and characterization of oxy-naphthenic acids in oilfield
      wastewater.
AB  - Oxy-naphthenic acids (oxy-NAs) are one of the major components of NA mixtures in
      wastewaters from petroleum industries. The limited available data indicated that
      oxy-NAs were considered as a potential marker for the degradation of NAs, and
      some oxy-NAs exhibited endocrine disrupting activities. However, the lack of
      information on the structures and occurrences of oxy-NAs in oilfield wastewaters
      limited the interpretations of the biotransformation pathways of NAs and
      structure-specific toxicity. A sensitive method for simultaneous determination of
      oxy-NAs together with NAs was developed by combining MAX extraction column and
      UPLC-ESI(-)-QTOF-MS. The 2000-fold SPE preconcentration step was highly specific
      for acids and the prewash solvent greatly reduced matrix effects in the UPLC-ESI(
      )-QTOF-MS analysis, resulting in an increase in sensitivity down to detection
      limits in the ng/L range. To provide structural information within each oxy-NA
      isomer class, a new method was developed by derivatizing oxy-NAs with dansyl
      chloride by UPLC-ESI(+)-QTOF-MS. The molecular ion dansyl derivatives from the
      corresponding oxy-NAs and characteristic fragmentation ions, not detected before
      derivatization, were observed in the extracts of oilfield wastewater, providing
      evidence that O3-NAs and O4-NAs were mainly composed of OH-NAs and (OH)2-NAs,
      respectively. Semiquantification of oxy-NAs and NAs in various oilfield
      wastewaters revealed NAs, O3-NAs, and O4-NAs present at concentrations of 187
      397, 44-146, and 40-108 MUg/L, respectively. Significantly different profiles of
      NA mixtures were observed in petroleum refinery wastewater and oil sands
      extraction water, but the profile of oxy-NAs was similar to NAs in different
      wastewaters suggesting the existence of biotransformation between NAs and oxy-NAs
      in the environment, and hydroxylation could be one of the major biotransformation
      pathways of NAs. 

PMID- 23859601
TI  - Novel antimicrobial metabolites produced by Sika deer-associated Actinomyces sp.
      JN411010.
AB  - Three novel metabolites (1, 5 and 10) were isolated from a 25-L fermentation
      broth of Actinomyces sp. JN411010 together with 11 related compounds. Their
      structures were determined on the basis of 1D and 2D NMR, as well as HR-ESI-MS
      spectroscopic data analyses. Compounds 1-2, 5-8 and 10 displayed moderate
      antimicrobial activities against Gram-positive and Gram-negative bacteria.
      Biosynthetic pathway of 5 and 10 was proposed to be catalysed by polyketide and
      non-ribosomal peptide gene clusters, respectively. 

PMID- 23859603
TI  - Heterophoria adaptation during the viewing of 3D stereoscopic stimuli.
AB  - PURPOSE: In this experiment two hypotheses were tested. The first hypothesis was
      that viewing 3D stereoscopic stimuli which are located geometrically beyond the
      screen on which the images are displayed would induce exophoric heterophoria
      (phoria) changes (adaptation). The second hypothesis was that participants whose
      phoria changed as a consequence of adaptation during the viewing of the
      stereoscopic stimuli would experience less visual discomfort than people whose
      phoria did not adapt. METHODS: Twenty participants aged between 19 and 45 were
      recruited to play a computer game in 3D and 2D conditions for 20 min each.
      Heterophoria was measured before and after viewing the stimuli, and visual
      discomfort was assessed by questionnaire on both occasions. RESULTS:
      Statistically significant changes in heterophoria were found in the 3D conditions
      (p = 0.007), but not in the 2D conditions (p = 0.16). The difference between the
      two conditions was statistically significant (p = 0.035). On average, there were
      also significant differences in visual discomfort between pre and post viewing,
      for both 2D and 3D conditions, however not everyone reported experiencing
      discomfort. The sample was then divided into groups, those who had reported an
      increase in discomfort whilst viewing 3D stimuli, and those who had not. No
      significant differences in heterophoria, or heterophoria change, were found
      between these two groups. CONCLUSIONS: The present study has shown that
      heterophoria can change as a result of viewing 3D stereoscopic stimuli, a change
      which is similar to prism adaptation. There was appreciable variability in the
      magnitude of this adaptation between individuals, but there was no correlation
      between the heterophoria change and visual discomfort.

PMID- 23859604
TI  - Construction of the tricyclic A-B-C core of the Veratrum alkaloids.
AB  - Organocatalyzed enantioselective allylation of 2-iodocyclohexenone followed by
      methylation and oxy-Cope rearrangement delivered enantiomerically enriched 2
      methyl 3-allyl cyclohexanone, which engaged in acid-catalyzed Robinson annulation
      to give the bicyclic enone. Subsequent elaboration of the pendant allyl group
      into an alpha-diazo beta-keto ester set the stage for Rh-mediated cyclization to
      deliver the tricyclic A-B-C core of the Veratrum alkaloids. 

PMID- 23859602
TI  - Electron flow through nitrotyrosinate in Pseudomonas aeruginosa azurin.
AB  - We have designed ruthenium-modified Pseudomonas aeruginosa azurins that
      incorporate 3-nitrotyrosine (NO2YOH) between Ru(2,2'
      bipyridine)2(imidazole)(histidine) and Cu redox centers in electron transfer (ET)
      pathways. We investigated the structures and reactivities of three different
      systems: RuH107NO2YOH109, RuH124NO2YOH122, and RuH126NO2YOH122. RuH107NO2YOH109,
      unlabeled H124NO2YOH122, and unlabeled H126NO2YOH122 were structurally
      characterized. The pKa's of NO2YOH at positions 122 and 109 are 7.2 and 6.0,
      respectively. Reduction potentials of 3-nitrotyrosinate (NO2YO(-))-modified
      azurins were estimated from cyclic and differential pulse voltammetry data:
      oxidation of NO2YO(-)122 occurs near 1.1 versus NHE; oxidation of NO2YO(-)109 is
      near 1.2 V. Our analysis of transient optical spectroscopic experiments indicates
      that hopping via NO2YO(-) enhances Cu(I) oxidation rates over single-step ET by
      factors of 32 (RuH107NO2YO(-)109), 46 (RuH126NO2YO(-)122), and 13 (RuH124NO2YO(
      )122). 

PMID- 23859605
TI  - Burns due to wet wood ash: three cases.
AB  - Wood ash, a traditional multipurpose agent, is sometimes used under occlusion as
      a folkloric prescription to ease pain and edema. Adding water or oil to ash forms
      a mixture with strong alkaline properties. We present three interesting cases who
      sustained full-thickness burns after application of a poultice of wetted wood ash
      for the treatment of leg pain.

PMID- 23859606
TI  - The antiviral drug acyclovir is a slow-binding inhibitor of (D)-amino acid
      oxidase.
AB  - d-Amino acid oxidase (DAO) is a degradative enzyme that is stereospecific for d
      amino acids, including d-serine and d-alanine, which are believed to be
      coagonists of the N-methyl-d-aspartate (NMDA) receptor. To identify a new class
      of DAO inhibitor(s) that can be used to elucidate the molecular details of the
      active site environment of DAO, manifold biologically active compounds of
      microbial origin and pre-existing drugs were screened for their ability to
      inhibit DAO activity, and several compounds were identified as candidates. One of
      these compounds, acyclovir (ACV), a well-known antiviral drug used for the
      treatment of herpesvirus infections, was characterized and evaluated as a novel
      DAO inhibitor in vitro. Analysis showed that ACV acts on DAO as a reversible slow
      binding inhibitor, and interestingly, the time required to achieve equilibrium
      between DAO, ACV, and the DAO/ACV complex was highly dependent on temperature.
      The binding mechanism of ACV to DAO was investigated in detail by several
      approaches, including kinetic analysis, structural modeling of DAO complexed with
      ACV, and site-specific mutagenesis of an active site residue postulated to be
      involved in the binding of ACV. The results confirm that ACV is a novel, active
      site-directed inhibitor of DAO that can be a valuable tool for investigating the
      structure-function relationships of DAO, including the molecular details of the
      active site environment of DAO. In particular, it appears that ACV can serve as
      an active site probe to study the structural basis of temperature-induced
      conformational changes of DAO. 

PMID- 23859607
TI  - Rabies prevention and management of cats in the context of trap-neuter-vaccinate
      release programmes.
AB  - Domestic cats are an important part of many Americans' lives, but effective
      control of the 60-100 million feral cats living throughout the country remains
      problematic. Although trap-neuter-vaccinate-return (TNVR) programmes are growing
      in popularity as alternatives to euthanizing feral cats, their ability to
      adequately address disease threats and population growth within managed cat
      colonies is dubious. Rabies transmission via feral cats is a particular concern
      as demonstrated by the significant proportion of rabies post-exposure prophylaxis
      associated with exposures involving cats. Moreover, TNVR has not been shown to
      reliably reduce feral cat colony populations because of low implementation rates,
      inconsistent maintenance and immigration of unsterilized cats into colonies. For
      these reasons, TNVR programmes are not effective methods for reducing public
      health concerns or for controlling feral cat populations. Instead, responsible
      pet ownership, universal rabies vaccination of pets and removal of strays remain
      integral components to control rabies and other diseases. 

PMID- 23859608
TI  - Clinical applications and issues of oxygen saturation level measurements obtained
      from peripheral sites.
AB  - Studies have suggested that the saturated oxygen level within one's arterial
      blood can provide crucial information about the status of one's cardiopulmonary
      system. Currently, a popular and convenient approach is to obtain this vital
      physiological sign through non-invasive measurement on suitable peripheral sites
      such as a finger, toe or ear lobe. This measurement is known as the SpO2
      parameter. It has been increasingly adopted in not only clinical settings but
      also remote monitoring purposes. In order to measure this optical based
      parameter, light sources of both the red and infrared wavelengths are required.
      The most recognized waveform feature is the peripheral pulse or its AC component
      which is synchronized to each heartbeat. The AC component is superimposed on a
      constant DC baseline attributed to breathing efforts, sympathetic nervous system
      activities and thermoregulation. The popularity of the SpO2 parameter may be due
      to its viable cost, simplicity to build and portability. Moreover, the basic
      building blocks of a SpO2 based measurement consists of control, filtering and
      amplification functions that can easily be incorporated with an embedded system.
      In this review, a brief description of the SpO2 measurement, its normative values
      and technical issues in its application as a clinical monitor are discussed.

PMID- 23859609
TI  - Prevention of arsenic-mediated reproductive toxicity in adult female rats by high
      protein diet.
AB  - CONTEXT: The detrimental effects of arsenic on female reproductive functions may
      involve overt oxidative stress. Casein and pea [Pisum sativum Linn. (Fabaceae)]
      proteins have antioxidant properties. OBJECTIVE: To investigate the role of
      casein- and pea-supplemented high-protein diet (HPD) in utero-ovarian protection
      from arsenic toxicity. MATERIALS AND METHODS: Adult female Wistar rats were
      orally gavaged with vehicle (Gr-I) or arsenic at 3 ppm/rat/d (Gr-II and Gr-III)
      for 30 consecutive days, when they were maintained on either regular diet
      containing 18% protein (Gr-I and Gr-II), or HPD containing 27% protein in the
      form of casein (20%) and pea (7%) (Gr-III). Reproductive functions were evaluated
      using a battery of biochemical and histological techniques. RESULTS: As compared
      to Gr-I, the Gr-II rats suffered from loss of estrous cyclicity, reduction in
      weight (mg/100 g body weight) of ovary (Gr-I: 54.3 +/- 4.2 versus Gr-II: 35.8 +/-
      1.6; p < 0.001) and uterus (Gr-I: 161.7 +/- 24.6 versus Gr-II: 94.44 +/- 13.2; p
      < 0.05), utero-ovarian degeneration, attenuated ovarian activities (unit/mg
      tissue/h) of Delta(5), 3beta-hydroxysteroid dehydrogenase (Gr-I: 3.41 +/- 0.12
      versus Gr-II: 2.31 +/- 0.09; p < 0.01) and 17beta-hydroxysteroid dehydrogenase
      (Gr-I: 3.82 +/- 0.57 versus Gr-II: 1.24 +/- 0.19; p < 0.001), and decreased serum
      estradiol level (pg/ml) (Gr-I: 61.5 +/- 2.06 versus 34.1 +/- 2.34; p < 0.001).
      Ovarian DNA damage was preponderant with blatant generation of malondialdehyde
      (nM/mg tissue; Gr-I: 15.10 +/- 2.45 versus Gr-II: 29.51 +/- 3.44; p < 0.01) and
      attenuated superoxide dismutase activity (unit/mg tissue) (Gr-I: 2.18 +/- 0.19
      versus Gr-II: 1.33 +/- 0.18; p < 0.05). The Gr-III rats were significantly
      protected from these ill effects of arsenic. DISCUSSION AND CONCLUSION: HPD, by
      way of antioxidant properties, may find prospective role in the protection of
      reproductive damage caused by arsenic.

PMID- 23859611
TI  - A systems biology road map for the discovery of drugs targeting cancer cell
      metabolism.
AB  - Despite their different histological and molecular properties, different types of
      cancers share few essential functional alterations. Some of these cancer
      hallmarks may easily be studied in in vitro cultures, while others are related to
      the way in which tumors grow in vivo. According to the systems biology paradigm,
      complex cellular functions arise as system-level properties from the dynamic
      interaction of a large number of biomolecules. We previously newly defined four
      basic cancer cell properties derived from known cancer hallmarks amenable to
      system-level investigation in cell cultures: enhanced growth, altered response to
      apoptotic cues, genomic instability and inability to enter senescence following
      oncogenic signaling. Here we summarize the major properties of enhanced growth
      that is dependent on metabolism rewiring - in which glucose is mostly used by
      fermentation while glutamine provides nitrogen and carbon atoms for biosyntheses 
      and controlled by oncogene signaling. We then briefly review the major drugs
      used to target signaling pathways in preclinical and clinical studies, whose
      clinical efficacy is unfortunately severely limited by tumor resistance,
      substantially due to signaling cross-talk. We present a systems biology roadmap
      that integrates different types of mathematical models with conventional and post
      genomic biomolecular analyses that will provide a deeper mechanistic
      understanding of the links between metabolism and uncontrolled cancer cell
      growth. This approach is taken to be instrumental both in unraveling cancer's
      first principles and in designing novel drugs able to target one or more control
      or execution steps of the cancer rewired metabolism, in order to achieve
      permanent arrest of tumor development.

PMID- 23859612
TI  - Targeting the metabolism of cancer cells - a foreword.

PMID- 23859610
TI  - Memory decline shows stronger associations with estimated spatial patterns of
      amyloid deposition progression than total amyloid burden.
AB  - The development of amyloid imaging compounds has allowed in vivo imaging of
      amyloid deposition. In this study, we examined the spatial patterns of amyloid
      deposition throughout the brain using Pittsburgh Compound Blue ((11)C-PiB)
      positron emission tomography data from the Baltimore Longitudinal Study of Aging.
      We used a new methodology that allowed us to approximate spatial patterns of the
      temporal progression of amyloid plaque deposition from cross-sectional data. Our
      results are consistent with patterns of progression known from autopsy studies,
      with frontal and precuneus regions affected early and occipital and sensorimotor
      cortices affected later in disease progression--here, disease progression means
      lower-to-higher total amyloid burden. Furthermore, we divided participants into
      subgroups based on longitudinal change in memory performance, and demonstrated
      significantly different spatial patterns of the estimated progression of amyloid
      deposition between these subgroups. Our results indicate that the spatial pattern
      of amyloid deposition is related to cognitive performance and may be more
      informative than a biomarker reflecting total amyloid burden, the use of which is
      the current practice. This finding has broad implications for our understanding
      of the relationship between cognitive decline/resilience and amyloid deposition,
      as well as for the use of amyloid imaging as a biomarker in research and clinical
      applications.

PMID- 23859613
TI  - Glutamine, glucose and other fuels for cancer.
AB  - Tumor cells suffer a metabolic reprogramming which allows them to use metabolic
      fuels (glucose, glutamine, lipids) through anabolic fates to support their
      enhanced proliferation and other carcinogenesis-related features. The present
      review tries to address and summarize the broad and growing information available
      about this reprogramming, whose pieces, put together, make up a complex scheme
      that encompasses different complexity scales, from cells to systemic networks. 

PMID- 23859614
TI  - A dual role for sirtuin 1 in tumorigenesis.
AB  - Sirtuin 1 (SIRT1) is an NAD+-dependent histone deacetylase which regulates many
      normal physiological and pathological processes. In addition to its place in
      cellular energy metabolism, increasing evidence shows a role for SIRT1 in
      tumorigenesis, wherein it can function as either a tumor promoter or suppressor.
      Its function in malignancy varies with concentration, cellular location, temporal
      and spatial distribution, and regulation by upstream and downstream factors. In
      this mini-review, we present the existing data which implicates SIRT1 in
      tumorigenesis. 

PMID- 23859615
TI  - Targeted cancer therapeutics: biosynthetic and energetic pathways characterized
      by metabolomics and the interplay with key cancer regulatory factors.
AB  - Reprogramming of energy metabolism has recently been added to the list of
      hallmarks that define cancer. Cellular metabolism plays a central role in cancer
      initiation and progression to metastatic disease. Genotypic and phenotypic
      metabolic alterations are seen throughout tumourigenesis, allowing cancer cells
      to sustain increased rates of proliferation. Furthermore, this shift fuels
      necessary substrates for nucleotide, protein, and lipid synthesis to support cell
      growth. Beyond the 'Warburg effect', the widely observed increase in the
      glycolytic processing of glucose in cancer cells, numerous other metabolic
      changes have been characterized in cancer. Metabolomics provides a valuable
      platform for the investigation of the metabolic perturbations that occur in
      different disease states using a systems biology approach to determine metabolic
      profiles of biological samples. As cell metabolism is a complex network of
      interdependent pathways, local alterations will have an impact on overall tumor
      metabolism. In this review, we will highlight particular pathways, including
      glycolysis, nucleotide biosynthesis, lipid metabolism, and bioenergetics with an
      eye towards selected metabolic targets that may provide a novel approach to
      therapeutic development. Specific regulatory factors, including Myc, p53, HIF-1
      and mTOR are briefly highlighted, as well as the key signaling pathways that can
      affect cellular metabolism. To demonstrate the powerful utility of high
      throughput metabolite profiling techniques, we present a practical example of the
      metabolomic profiling of metastatic cells derived from a lung cancer metastasis
      model.

PMID- 23859616
TI  - Reprogrammed metabolism of cancer cells as a potential therapeutic target.
AB  - Metabolism in cancer cells is reprogrammed. Cancer cells largely depend on
      glycolysis for ATP production. The metabolic alterations in cancer cells
      facilitate resistance to cell death as well as biosynthesis of nucleotides and
      lipids, building blocks for growth. The reprogrammed metabolism is increasingly
      seen as a target in cancer therapy. This review describes the metabolic
      reprogramming of cancer cells and illustrates how this is related to cell cycle
      and apoptosis resistance. Is also describes various scenarios for targeting
      cancer cell metabolism and highlights options for interventions with nutrition
      and bioactive food components. 

PMID- 23859618
TI  - Pyruvate kinase M2: regulatory circuits and potential for therapeutic
      intervention.
AB  - Cancer cells are characterized by reprogramming of energy metabolism. Over the
      last decade, understanding of the metabolic changes that occur in cancer has
      increased dramatically, with great interest in targeting metabolism for cancer
      therapy. Pyruvate kinase isoenzyme type M2 (abbreviations: PKM2, M2-PK) plays a
      key role in modulating glucose metabolism to support cell proliferation. PKM2,
      like other PK isoforms, catalyzes the last energy-generating step in glycolysis,
      but is unique in its capacity to be regulated. PKM2 is regulated at several
      cellular levels, including gene expression, alternative splicing and post
      translational modification. In addition, PKM2 is regulated by key metabolic
      intermediates and interacts with more than twenty different proteins. Hence, this
      isoenzyme is an important regulator of glycolysis, and additionally functions in
      other novel roles that have recently emerged. Recent evidence indicates that
      intervening with the complex regulatory network of PKM2 has severe consequences
      on tumor cell proliferation, indicating the potential of this enzyme as a target
      for tumor therapy.

PMID- 23859617
TI  - Targeting SREBP-1-driven lipid metabolism to treat cancer.
AB  - Metabolic reprogramming is a hallmark of cancer. Oncogenic growth signaling
      regulates glucose, glutamine and lipid metabolism to meet the bioenergetics and
      biosynthetic demands of rapidly proliferating tumor cells. Emerging evidence
      indicates that sterol regulatory element-binding protein 1 (SREBP-1), a master
      transcription factor that controls lipid metabolism, is a critical link between
      oncogenic signaling and tumor metabolism. We recently demonstrated that SREBP-1
      is required for the survival of mutant EGFR-containing glioblastoma, and that
      this pro-survival metabolic pathway is mediated, in part, by SREBP-1-dependent
      upregulation of the fatty acid synthesis and low density lipoprotein (LDL)
      receptor (LDLR). These results have identified EGFR/PI3K/Akt/SREBP-1 signaling
      pathway that promotes growth and survival in glioblastoma, and potentially other
      cancer types. Here, we summarize recent insights in the understanding of cancer
      lipid metabolism, and discuss the evidence linking SREBP-1 with PI3K/Akt
      signaling-controlled glycolysis and with Myc-regulated glutaminolysis to lipid
      metabolism. We also discuss the development of potential drugs targeting the
      SREBP-1- driven lipid metabolism as anti-cancer agents.

PMID- 23859620
TI  - Acetylation control of cancer cell metabolism.
AB  - Lysine acetylation plays an essential role in metabolism. Five individual studies
      have identified that a large number of cellular proteins are potentially
      acetylated. Notably, almost every enzyme involved in central metabolic pathways
      such as glycolysis, the TCA cycle, fat acid metabolism, urea cycle and glycogen
      metabolism, is acetylated in response to nutrition fluctuations. Metabolic
      reprogramming is a critical hallmark during cancer development. Tumor cells
      preferentially utilize glycolysis instead of oxidative phosphorylation to produce
      more lactate and metabolic intermediates even under normal oxygen pressure, which
      was first noted as the "Warburg Effect". This review focuses on recent advances
      in the acetylation regulation of metabolic enzymes involved in the Warburg
      effect, the dysfunction of acetylation regulation in tumorigenesis and their
      potential role in cancer metabolism therapy. 

PMID- 23859621
TI  - Hand-foot syndrome: common presentation in an uncommon situation.

PMID- 23859622
TI  - Helicobacter pylori susceptible/resistant to antibiotic eradication therapy
      differ in the maturation and activation of dendritic cells.
AB  - BACKGROUND: The natural course of Helicobacter pylori infection, as well as the
      success of antibiotic eradication is determined by the immune response to
      bacteria. The aim of the study is to investigate how different Helicobacter
      pylori isolates influence the dendritic cells maturation and antigen-presenting
      function in order to elucidate the differences between Helicobacter pylori
      strains, isolated from the patients with successful antibiotic eradication
      therapy or repeated eradication failure. MATERIALS AND METHODS: Dendritic cells
      maturation and antigen presentation were monitored by flow cytometry analysis of
      the major histocompatibility complex class II (MHC-II), Toll-like receptor (TLR)
      and costimulatory molecules expression, and by determining cytokine secretion.
      RESULTS: Dendritic cells stimulated with Helicobacter pylori isolated from
      patients with repeated antibiotic eradication failure expressed less human
      leukocyte antigen (HLA-DR), CD86, TLR-2, and interleukin-8 (IL-8) compared to
      Helicobacter pylori strains susceptible to antibiotic therapy; the latter
      expressed lower production of IL-10. Polymyxin B inhibition of lipopolysaccharide
      reduces IL-8 secretion in the group of Helicobacter pylori strains susceptible to
      antibiotic therapy. The differences in IL-8 secretion between both groups are
      lipopolysaccharide dependent, while the differences in secretion of IL-10 remain
      unchanged after lipopolysaccharide inhibition. Inhibitor of cathepsin X Mab 2F12
      reduced the secretion of IL-6, and the secretion was significantly lower in the
      group of Helicobacter pylori strains isolated from patients with repeated
      antibiotic eradication failure. CONCLUSION: Helicobacter pylori strains,
      susceptible/resistant to antibiotic eradication therapy, differ in their
      capability to induce DCs maturation and antigen-presenting function.

PMID- 23859619
TI  - AMPK as a potential anticancer target - friend or foe?
AB  - Adenosine monophosphate-activated protein kinase (AMPK) is a key player in
      maintaining energy homeostasis in response to metabolic stress. Beyond diabetes
      and metabolic syndrome, there is a growing interest in the therapeutic
      exploitation of the AMPK pathway in cancer treatment in light of its unique
      ability to regulate cancer cell proliferation through the reprogramming of cell
      metabolism. Although many studies support the tumor-suppressive role of AMPK,
      emerging evidence suggests that the metabolic checkpoint function of AMPK might
      be overridden by stress or oncogenic signals so that tumor cells use AMPK
      activation as a survival strategy to gain growth advantage. These findings
      underscore the complexity in the cellular function of AMPK in maintaining energy
      homeostasis under physiological versus pathological conditions. Thus, this review
      aims to provide an overview of recent findings on the functional interplay of
      AMPK with different cell metabolic and signaling effectors, particularly histone
      deacetylases, in mediating downstream tumor suppressive or promoting mechanisms
      in different cell systems. Although AMPK activation inhibits tumor growth by
      targeting multiple signaling pathways relevant to tumorigenesis, under certain
      cellular contexts or certain stages of tumor development, AMPK might act as a
      protective response to metabolic stresses, such as nutrient deprivation, low
      oxygen, and low pH, or as downstream effectors of oncogenic proteins, including
      androgen receptor, hypoxia-inducible factor-1alpha, c-Src, and MYC. Thus,
      investigations to define at which stage(s) of tumorigenesis and cancer
      progression or for which genetic aberrations AMPK inhibition might represent a
      more relevant strategy than AMPK activation for cancer treatment are clearly
      warranted. 

PMID- 23859624
TI  - Bonded boojum-colloids in nematic liquid crystals.
AB  - We investigate bonded boojum-colloids in nematic liquid crystals, configurations
      where two colloids with planar degenerate anchoring are double-bonded through
      line defects connecting their surfaces. This bonded structure promotes the
      formation of linear chains aligned with the nematic director. We show that the
      bonded configuration is the global minimum in systems that favor twist
      deformations. In addition, we investigate the influence of confinement on the
      stability of bonded boojum-colloids. Although the unbonded colloid configuration,
      where the colloids bundle at oblique angles, is favored by confinement, the
      bonded configuration is again the global minimum for liquid crystals with
      sufficiently small twist elastic constants. 

PMID- 23859623
TI  - New fluorescent substrate enables quantitative and high-throughput examination of
      vesicular monoamine transporter 2 (VMAT2).
AB  - Vesicular monoamine transporter 2 (VMAT2) is an essential component of the
      monoaminergic neurotransmission system in the brain as it transports monoamine
      neurotransmitters from the neuronal cytosol into the synaptic vesicles and thus
      contributes to modulation of neurotransmitter release. Considering the continuing
      interest in VMAT2 as a drug target, as well as a target for the design of imaging
      probes, we have developed a fluorescent substrate well suited for the study of
      VMAT2 in cell culture. Herein, we report the synthesis and characterization of a
      new fluorescent probe, FFN206, as an excellent VMAT2 substrate capable of
      detecting VMAT2 activity in intact cells using fluorescence microscopy, with
      subcellular localization to VMAT2-expressing acidic compartments without apparent
      labeling of other organelles. VMAT2 activity can also be measured via microplate
      reader. The apparent Km of FFN206 at VMAT2 was found to be 1.16 +/- 0.10 MUM,
      similar to that of dopamine. We further report the development and validation of
      a cell-based fluorescence assay amenable to high-throughput screening (HTS) using
      VMAT2-transfected HEK cells (Z'-factor of 0.7-0.8), enabling rapid identification
      of VMAT2 inhibitors and measurement of their inhibition constants over a broad
      range of affinities. FFN206 thus represents a new tool for optical examination of
      VMAT2 function in cell culture. 

PMID- 23859625
TI  - Manual-guided cognitive-behavioural therapy for insomnia delivered by ordinary
      primary care personnel in general medical practice: a randomized controlled
      effectiveness trial.
AB  - Chronic insomnia is a prevalent problem in primary health care and tends to be
      more serious than insomnia in the general population. These patients often obtain
      little benefit from hypnotics, and are frequently open to exploring various
      options for medical treatment. However, most general practitioners (GPs) are
      unable to provide such options. Several meta-analyses have shown that cognitive
      behavioural therapy (CBT) for insomnia results in solid improvements on sleep
      parameters, and a few studies have demonstrated promising results for nurse
      administered CBT in primary care. The aim of this randomized controlled study was
      to investigate the clinical effectiveness of manual-guided CBT for insomnia
      delivered by ordinary primary care personnel in general medical practice with
      unselected patients. Sixty-six primary care patients with insomnia were
      randomized to CBT or a waiting-list control group. The CBT group improved
      significantly more than the control group using the Insomnia Severity Index as
      the outcome. The effect size was high. Sleep diaries showed a significant, medium
      sized treatment effect for sleep onset latency and wake time after sleep onset.
      However, for all measures there is a marked deterioration at follow-up
      assessments. Almost half of the treated subjects (47%) reported a clinically
      relevant treatment effect directly after treatment. It is concluded that this way
      of delivering treatment may be cost-effective. 

PMID- 23859626
TI  - The disproportionate economic burden associated with severe and complicated
      obesity: a systematic review.
AB  - Burden of disease studies typically classify individuals with a body mass index
      (BMI) >= 30 kg m(-2) as a single group ('obese') and make comparisons to those
      with lower BMIs. Here, we review the literature on the additional economic burden
      associated with severe obesity or classes 3 and 4 obesity (BMI >= 40 kg m(-2) ),
      the fastest growing category of obesity, with the aim of exploring and
      disaggregating differences in resource use as BMI increases beyond 40 kg m(-2) .
      We recognize the importance of comparing classes 3 and 4 obesity to less severe
      obesity (classes 1 and 2) as well as quantifying the single sub-class impacts
      (classes 3 and 4). Although the latter analysis is the aim of this review, we
      include results, where found in the literature, for movement between the
      recognized subclasses and within classes 3 and 4 obesity. Articles presenting
      data on the economic burden associated with severe obesity were identified from a
      search of Ovid MEDLINE, EMBASE, EBSCO CINAHL and Cochrane Library databases. Data
      were extracted on the direct costs, productivity costs and resource use
      associated with severe obesity along with estimates of the multiplier effects
      associated with increasing BMI. Fifteen studies were identified, of which four
      disaggregated resource use for BMI >= 40 kg m(-2) . The multiplier effects
      derived for a variety of different types of costs incurred by the severely obese
      compared with those of normal weight (18.5 kg m(-2)  < BMI < 25 kg m(-2) ) ranged
      from 1.5 to 3.9 for direct costs, and from 1.7 to 8.0 for productivity costs.
      There are few published data on the economic burden of obesity disaggregated by
      BMI >= 40 kg m(-2) . By grouping people homogenously above a threshold of BMI 40
      kg m(-2) , the multiplier effects for those at the highest end of the spectrum
      are likely to be underestimated. This will, in turn, impact on the estimates of
      cost-effectiveness for interventions and policies aimed at the severely obese. 

PMID- 23859627
TI  - Symmetry breaking and hole localization in multiple core electron ionization.
AB  - Motivated by recent opportunitites to study hollow molecules with multiple core
      holes offered by X-ray free electron lasers, we revisit the core-hole
      localization and symmetry breaking problem, now studying ionization of more than
      one core electron. It is shown, using a N2 molecule with one, two, three, and
      four core holes, for example, that in a multiconfigurational determination of the
      core ionization potentials employing a molecular point group with broken
      inversion symmetry, one particular configuration is sufficient to account for the
      symmetry breaking relaxation energy in an independent particle approximation in
      the case of one or three holes, whereas the choice of point group symmetry is
      unessential for two and four holes. The relaxation energy follows a quadratic
      dependence on the number of holes in both representations. 

PMID- 23859628
TI  - A tenuous result: re-analysis of the link between Internet usage and young
      adults' driving license holding. Comments on "Recent changes in the age
      composition of drivers in 15 countries".

PMID- 23859629
TI  - Improving the binding characteristics of tripodal compounds on single layer
      graphene.
AB  - Graphene is an atomically thin, transparent, and conductive electrode material of
      interest for sensors and energy conversion and storage devices, among others.
      Fully realizing its potential will require robust and general methods to anchor
      active functionality onto its pristine basal plane. Such strategies should not
      utilize covalent bond formation, which disrupts the graphene's pi-electron
      system, from which most of its desirable properties arise. We recently introduced
      a tripodal binding motif, which forms robust monolayers on graphene capable of
      immobilizing active proteins and preventing their denaturation. Here we describe
      structure-property relationships for a series of tripod binding groups with
      "feet" of different sizes. Each derivative adsorbs strongly (DeltaGads ~ -39 kJ
      mol(-1)) to graphene's basal plane, yet the resulting monolayers exhibit kinetic
      stabilities that vary over 2 orders of magnitude and molecular densities that
      vary by a factor of 2. This study identifies phenanthrene as a superior anchor
      relative to pyrene on the basis of its increased monolayer density and similar
      kinetic stability. We also demonstrate that varying the length of the methylene
      linkers between the feet and tripodal core does not affect binding substantially.
      These results represent the first demonstration of structure-property
      relationships in the assembly of molecular adsorbates on graphene and provide a
      paradigm for designing effective graphene binding motifs. 

PMID- 23859630
TI  - Metabolomics in cerebrospinal fluid of patients with amyotrophic lateral
      sclerosis: an untargeted approach via high-resolution mass spectrometry.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by the absence of reliable
      diagnostic biomarkers. The aim of the study was to (i) devise an untargeted
      metabolomics methodology that reliably compares cerebrospinal fluid (CSF) from
      ALS patients and controls by liquid chromatography coupled to high-resolution
      mass spectrometry (LC-HRMS); (ii) ascertain a metabolic signature of ALS by use
      of the LC-HRMS platform; (iii) identify metabolites for use as diagnostic or
      pathophysiologic markers. We developed a method to analyze CSF components by UPLC
      coupled with a Q-Exactive mass spectrometer that uses electrospray ionization.
      Metabolomic profiles were created from the CSF obtained at diagnosis from ALS
      patients and patients with other neurological conditions. We performed
      multivariate analyses (OPLS-DA) and univariate analyses to assess the
      contribution of individual metabolites as well as compounds identified in other
      studies. Sixty-six CSF samples from ALS patients and 128 from controls were
      analyzed. Metabolome analysis correctly predicted the diagnosis of ALS in more
      than 80% of cases. OPLS-DA identified four features that discriminated diagnostic
      group (p < 0.004). Our data demonstrate that untargeted metabolomics with LC-HRMS
      is a robust procedure to generate a specific metabolic profile for ALS from CSF
      and could be an important aid to the development of biomarkers for the disease. 

PMID- 23859631
TI  - Culmination of low-dose pesticide effects.
AB  - Pesticides applied in agriculture can affect the structure and function of
      nontarget populations at lower doses and for longer timespans than predicted by
      the current risk assessment frameworks. We identified a mechanism for this
      observation. The populations of an aquatic invertebrate (Culex pipiens) exposed
      over several generations to repeated pulses of low concentrations of the
      neonicotinoid insecticide (thiacloprid) continuously declined and did not recover
      in the presence of a less sensitive competing species (Daphnia magna). By
      contrast, in the absence of a competitor, insecticide effects on the more
      sensitive species were only observed at concentrations 1 order of magnitude
      higher, and the species recovered more rapidly after a contamination event. The
      underlying processes are experimentally identified and reconstructed using a
      simulation model. We conclude that repeated toxicant pulse of populations that
      are challenged with interspecific competition may result in a multigenerational
      culmination of low-dose effects. 

PMID- 23859632
TI  - Cancer stem-like cells and epithelial-mesenchymal transition-utility of
      biomarkers in diagnostic pathology.

PMID- 23859634
TI  - Direct arylation of oligonaphthalenes using PIFA/BF3.Et2O: from double arylation
      to larger oligoarene products.
AB  - Direct dehydrogenative coupling between the linear ter- and quaternaphthalenes
      and substituted benzenes was achieved under the Kita conditions using the
      hypervalent PIFA/BF3 reagent. Products resulting from either the double arylation
      of the naphthalenic substrate or the formal dimerizative arylation have been
      prepared. For example, in the latter mode, ternaphthalene was converted into a
      series of linear octiarenes (counting the capping Ar). The process represents an
      alternative to the cross-coupling methodologies employed in related syntheses and
      proceeds via a selective functionalization of six relatively inert aromatic CH
      bonds. 

PMID- 23859633
TI  - Odontogenic induction of dental stem cells by extracellular matrix-inspired three
      dimensional scaffold.
AB  - Currently, root canal therapy is the only clinical treatment available to treat
      damaged or necrotic dental pulp tissue arising from caries. This treatment
      results in the loss of tooth vitality. Somatic dental stem cell-based tissue
      engineering approaches can alleviate this problem by preserving tooth vitality.
      Dental stem cells are multipotent and under appropriate conditions could be used
      for dental pulp tissue engineering. Successful use of these cells in pulp repair
      requires a combination of growth factors and appropriate scaffolds to induce cell
      differentiation. In this study, we demonstrate the odontogenic differentiation of
      human dental pulp stem cells (DPSCs) and the human periodontal ligament stem
      cells when cultured on a decellularized 3D extracellular matrix (ECM) scaffold
      without the need for exogenous addition of growth factors. Subcutaneous
      implantation of the ECM scaffolds containing DPSCs showed the formation of dental
      pulp-like tissue with cells expressing dentin sialoprotein (DSP) and dentin
      phosphophoryn (DPP). Additionally, we also show that the ECM scaffold can be
      exploited as a tool to study the extracellular function of multifunctional
      proteins. These promising results demonstrate the feasibility of developing these
      biomimetic scaffolds for treatment of dental caries. 

PMID- 23859635
TI  - Correlation between serum 25-hydroxyvitamin D level and plasminogen activator
      inhibitor 1 in type 2 diabetic patients.
AB  - INTRODUCTION: It has been approved that vitamin D deficiency has a role in
      increasing the rate of cardio-vascular diseases in diabetic patients with unknown
      mechanism. The effects of vitamin D on hemostasis and its inflammatory mechanisms
      have been proposed as possible causes of cardio-vascular diseases in these
      patients. Also, high level of plasminogen activator inhibitor- type 1 (PAI-1) has
      been identified as a risk factor for cardio-vascular diseases in diabetic
      patients. The goal of this survey was to investigate the relation between vitamin
      D level and level of PAI-1 as a thrombotic marker. PATIENTS AND METHODS: 180
      patients with type 2 diabetes mellitus enrolled for the study. The serum level of
      PAI-1 was measured by enzyme linked immune-assay and was compared with calcium
      metabolism markers including vitamin D, parathormon hormone, fasting blood sugar,
      calcium, and phosphorous. RESULTS: There was statistically significant relation
      between PAI-1 with fasting blood sugar and high density lipoprotein, but there
      was no significant relation between PAI-1 with vitamin D level and other cardio
      vascular disease variables. DISCUSSION: It seems that serum level of vitamin D
      has no relation with PAI-1 in diabetic patients, although further investigations
      are required to confirm these findings.

PMID- 23859636
TI  - Active immunization against tumor necrosis factor-alpha decreases proinflammatory
      cytokines, oxidative stress mediators and adhesion molecules risk factors in
      streptozotocin-induced diabetic rats.
AB  - Diabetes is now one of the most common un-communicable diseases worldwide. Few
      studies have dealt specifically with the potential therapeutic effect of TNF
      alpha suppressor to decrease oxidative stress markers in patients with diabetes.
      The aim of this study was to investigate the potential therapeutic and toxic
      effect of the direct injection of the anti-TNF-alpha on oxidative stress
      mediators, proinflammatory cytokines and vascular risk factors associated with
      diabetes on diabetic rats. METHODS: diabetes was induced by streptozotocin, three
      weeks after the - induction of diabetes, a polyclonal anti-mouse/rat TNF-alpha
      rabbit serum was injected in the treated group and sacrificed after 4 weeks. The
      expression of TNF-alpha mRNA was measured by RT-PCR. The levels of TNF-alpha,
      VEGF, IL-2, IL- 6, HSP-70, troponin-t, 8-OHdG, ICAM-1 and VCAM-1 were evaluated
      using ELISA. Myeloperoxiase (MPO) and total peroxides (TPs) levels were estimated
      by biochemical reactions. RESULTS: the treatment of diabetic rats with the anti
      TNF-alpha caused a significant decrease in the TNF-alpha mRNA expression, which
      were paralleled with the decreased levels of TNF-alpha, IL-6, MOP, HSP-70, ICAM
      1, VCAM-1, troponin-t and 8-OHdG in the blood serum. On the contrary, all were
      highly expressed in the diabetic group that may be the leading reasons for the
      DNA damage and cell loss. Data revealed that TNF-alpha, HSP-70, IL-6, MPO and
      adhesion molecules when expressed in diabetic rats, collectively induce dramatic
      changes. CONCLUSION: these new findings suggested that targeting TNF-alpha could
      effectively reduce expressions of MCP-1, HSP-70, troponin-t, 8-OHdG and VCAM- 1,
      along with prominent reduction in MPO and IL-6 levels.

PMID- 23859637
TI  - STAR splicing mutations cause the severe phenotype of lipoid congenital adrenal
      hyperplasia: insights from a novel splice mutation and review of reported cases.
AB  - OBJECTIVE: The steroidogenic acute regulatory protein (StAR) transports
      cholesterol to the mitochondria for steroidogenesis. Loss of StAR function causes
      lipoid congenital adrenal hyperplasia (LCAH) which is characterized by impaired
      synthesis of adrenal and gonadal steroids causing adrenal insufficiency, 46,XY
      disorder of sex development (DSD) and failure of pubertal development. Partial
      loss of StAR activity may cause adrenal insufficiency only. PATIENT: A newborn
      girl was admitted for mild dehydration, hyponatremia, hyperkalemia and
      hypoglycaemia and had normal external female genitalia without hyperpigmentation.
      Plasma cortisol, 17OH-progesterone, DHEA-S, androstendione and aldosterone were
      low, while ACTH and plasma renin activity were elevated, consistent with the
      diagnosis of primary adrenal insufficiency. Imaging showed normal adrenals, and
      cytogenetics revealed a 46,XX karyotype. She was treated with fluids,
      hydrocortisone and fludrocortisone. DESIGN, METHODS AND RESULTS: Genetic studies
      revealed a novel homozygous STAR mutation in the 3' acceptor splice site of
      intron 4, c.466-1G>A (IVS4-1G>A). To test whether this mutation would affect
      splicing, we performed a minigene experiment with a plasmid construct containing
      wild-type or mutant StAR gDNA of exons-introns 4-6 in COS-1 cells. The splicing
      was assessed on total RNA using RT-PCR for STAR cDNAs. The mutant STAR minigene
      skipped exon 5 completely and changed the reading frame. Thus, it is predicted to
      produce an aberrant and shorter protein (p.V156GfsX19). Computational analysis
      revealed that this mutant protein lacks wild-type exons 5-7 which are essential
      for StAR-cholesterol interaction. CONCLUSIONS: STAR c.466-1A skips exon 5 and
      causes a dramatic change in the C-terminal sequence of the protein, which is
      essential for StAR-cholesterol interaction. This splicing mutation is a loss-of
      function mutation explaining the severe phenotype of our patient. Thus far, all
      reported splicing mutations of STAR cause a severe impairment of protein function
      and phenotype.

PMID- 23859639
TI  - Development of mucoadhesive floating hollow beads of acyclovir with
      gastroretentive properties.
AB  - This study aimed at improving the oral bioavailability of acyclovir (ACV) through
      incorporating it into gastroretentive dosage form based on floating hollow
      chitosan beads. Hollow chitosan beads were prepared using a solvent free,
      ionotropic gelation method. The effect of formulation parameters, including
      chitosan molecular weight and drug concentration, on bead characteristics was
      studied. The drug containing formulations had yields >70.5 +/- 0.31%. The
      entrapment efficiencies for the medium molecular weight chitosan formulations
      (56.29 +/- 0.94%-62.75 +/- 0.86%) was greater than the high molecular weight
      chitosan formulation (29.21 +/- 0.89%). The density of all formulations was below
      that of gastric fluid, the greatest density observed was 0.60 +/- 0.01 g cm(-3).
      Unsurprisingly, the formulations were immediate bouyant to different degrees in
      both pH 1.2 and pH 6.8 media. In addition, the chitosan beads were all seen to
      swell in pH 1.2 media and demonstrated mucoadhesive properties. A sustained
      release profile was observed from the chitosan beads, the developed formulations
      released drug at slower rates than a marketed ACV oral tablet. The developed
      system has the dual advantages of being gastroretentive, to increase oral
      bioavailability and releasing drug in a controlled manner, to reduce the required
      frequency of administration thereby promoting patient adherence.

PMID- 23859638
TI  - Retention of participants in medication-assisted programs in low- and middle
      income countries: an international systematic review.
AB  - BACKGROUND AND AIMS: Medication-assisted treatment (MAT) is a key component in
      overdose prevention, reducing illicit opiate use and risk of blood-borne virus
      infection. By retaining participants in MAT programs for longer periods of time,
      more noticeable and permanent changes in drug use, risk behavior and quality of
      life can be achieved. Many studies have documented retention in MAT programs in
      high-income countries, using a 50% average 12-month follow-up retention rate as a
      marker for a successful MAT program. This study contributes to a systematic
      understanding of how successful programs have been in retaining participants in
      low- and middle-income countries (LMIC) over time. METHODS: Using Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we
      conducted a systematic literature search to identify MAT program studies that
      documented changes in retention over time for participants in buprenorphine and
      methadone programs in LMIC. Retention was measured for participants by length of
      follow-up, type of MAT and treatment dosage. RESULTS: There were 58 MAT program
      studies, with 27 047 participants eligible for inclusion in the review. Overall
      average retention after 12 months was 54.3% [95% confidence interval (CI) = 46.2,
      63.7%]. Overall average retention was moderately good for both buprenorphine
      (48.3%, 95% CI = 22.1, 74.6%) and methadone (56.6%, 95% CI = 45.9%, 67.3%) after
      12 months of treatment. Among programs using methadone there was no statistically
      significant difference in average retention by dosage level, and the 10 highest
      and lowest dosage programs obtained similar average retention levels after 12
      months. CONCLUSION: Medication-assisted treatment programs in low- and middle
      income countries achieve an average 50% retention rate after 12 months, with wide
      variation across programs but little difference between those using buprenorphine
      versus methadone.

PMID- 23859640
TI  - Synthetically prepared glycooligosaccharides mimicking Candida albicans cell wall
      glycan antigens--novel tools to study host-pathogen interactions.
AB  - The immunobiological efficacy of synthetically prepared mannooligosaccharides and
      a glucooligosaccharide mimicking the structure of Candida albicans cell wall
      glycans was assessed in vivo and in vitro to exploit immune responses. The
      exposure of mice splenocytes to BSA-based conjugates of synthetic oligomannosides
      and oligoglucoside revealed intense influence on T-cell subset polarization. The
      conjugates biased the immune responses towards Th1 and Th17 with respect to the
      prevalence of interferon-gamma (IFN-gamma) and interleukin (IL)-17 (IL-17) over
      IL-4 and IL-10 levels. The inflammatory activity of the conjugates has been
      evaluated based on the induction of pro-inflammatory cytokines. Postvaccination,
      antimannooligosaccharide and antiglucooligosaccharide antisera were subjected to
      an evaluation of the structure-immunomodulation activity relationship. Clinical
      isolates of C. albicans CCY 29-3-32 and C. albicans CCY 29-3-164 were applied to
      study interactions between Candida cells and anti-oligosaccharide antibodies. In
      situ recognition of parietal oligomannosyl and oligoglucosyl sequences in C.
      albicans cell wall by the antisera raised against BSA-based conjugates of
      synthetic oligomannosides and oligoglucoside revealed the effective recognition
      of specific distribution of natural oligosaccharide sequences in the cell wall of
      C. albicans serotype A. With respect to these results, it can be concluded that
      new, synthetically prepared oligosaccharides mimicking Candida cell wall
      structures represent prospective immunobiologically effective components for
      further immunopharmacologically relevant Candida vaccine design. 

PMID- 23859641
TI  - Effects on the quality of the nursing care process through an educational program
      and the use of electronic nursing documentation.
AB  - PURPOSE: To evaluate the effect of the educational program "Guided Clinical
      Reasoning" (GCR) and the introduction of an intelligent electronic nursing
      documentation system (e-doc) on the quality of the nursing process. METHODS:
      Evaluation was conducted at three measurement points and rated with the
      instrument "Quality of Nursing Diagnoses, Interventions and Outcomes" (Q-DIO).
      FINDINGS: GCR showed the best Q-DIO-scores. No long-term effect was found after
      GCR cessation. The e-doc delivered the lowest scores, while showing adequate
      support in using nursing diagnoses. CONCLUSIONS: E-docs can support conducting
      the nursing process, but for meaningful e-doc use, clinical reasoning is
      essential. IMPLICATIONS: High-quality nursing documentation requires recognition
      of factors obstructing or supporting nurses in the use of e-docs while conducting
      the nursing process.

PMID- 23859642
TI  - Brain activation during masked and unmasked semantic priming: commonalities and
      differences.
AB  - Using fMRI during a lexical decision task, we investigated the neural correlates
      of semantic priming under masked and unmasked prime presentation conditions in a
      repeated measurement design of the same group of 24 participants (14 women). The
      task was to discriminate between pseudowords and words. Masked and unmasked prime
      words differed in their degree of semantic relatedness with target stimuli.
      Neural correlates of priming were defined as significantly different neural
      activations upon semantically unrelated minus related trials. Left fusiform
      gyrus, left posterior inferior frontal gyrus, and bilateral pre-SMA showed
      priming effects independent of the masking condition. By contrast, bilateral
      superior temporal gyri, superior parietal lobules, and the SMA proper
      demonstrated greater neural priming in the unmasked compared with the masked
      condition. The inverted contrast (masked priming minus unmasked priming) did not
      show significant differences even at lowered thresholds of significance. The
      conjoint effects of priming in the left fusiform gyrus suggest its involvement as
      a direct consequence of the neural organization of semantic memory. Activity in
      brain regions showing significantly more neural priming in the unmasked condition
      possibly reflected participants' evaluation of the prime-target relationship,
      presumably in the context of semantic matching. The present results therefore
      indicate that masked and unmasked semantic priming partially depend on
      dissociable mechanisms at the neural and most likely also at the functional
      level. 

PMID- 23859643
TI  - Blue light stimulates cognitive brain activity in visually blind individuals.
AB  - Light regulates multiple non-image-forming (or nonvisual) circadian,
      neuroendocrine, and neurobehavioral functions, via outputs from intrinsically
      photosensitive retinal ganglion cells (ipRGCs). Exposure to light directly
      enhances alertness and performance, so light is an important regulator of
      wakefulness and cognition. The roles of rods, cones, and ipRGCs in the impact of
      light on cognitive brain functions remain unclear, however. A small percentage of
      blind individuals retain non-image-forming photoreception and offer a unique
      opportunity to investigate light impacts in the absence of conscious vision,
      presumably through ipRGCs. Here, we show that three such patients were able to
      choose nonrandomly about the presence of light despite their complete lack of
      sight. Furthermore, 2 sec of blue light modified EEG activity when administered
      simultaneously to auditory stimulations. fMRI further showed that, during an
      auditory working memory task, less than a minute of blue light triggered the
      recruitment of supplemental prefrontal and thalamic brain regions involved in
      alertness and cognition regulation as well as key areas of the default mode
      network. These results, which have to be considered as a proof of concept, show
      that non-image-forming photoreception triggers some awareness for light and can
      have a more rapid impact on human cognition than previously understood, if brain
      processing is actively engaged. Furthermore, light stimulates higher cognitive
      brain activity, independently of vision, and engages supplemental brain areas to
      perform an ongoing cognitive process. To our knowledge, our results constitute
      the first indication that ipRGC signaling may rapidly affect fundamental cerebral
      organization, so that it could potentially participate to the regulation of
      numerous aspects of human brain function. 

PMID- 23859644
TI  - Disruption of visual awareness during the attentional blink is reflected by
      selective disruption of late-stage neural processing.
AB  - Any information represented in the brain holds the potential to influence
      behavior. It is therefore of broad interest to determine the extent and quality
      of neural processing of stimulus input that occurs with and without awareness.
      The attentional blink is a useful tool for dissociating neural and behavioral
      measures of perceptual visual processing across conditions of awareness. The
      extent of higher-order visual information beyond basic sensory signaling that is
      processed during the attentional blink remains controversial. To determine what
      neural processing at the level of visual-object categorization occurs in the
      absence of awareness, electrophysiological responses to images of faces and
      houses were recorded both within and outside the attentional blink period during
      a rapid serial visual presentation stream. Electrophysiological results were
      sorted according to behavioral performance (correctly identified targets vs.
      missed targets) within these blink and nonblink periods. An early index of face
      specific processing (the N170, 140- to 220-msec poststimulus) was observed
      regardless of whether the participant demonstrated awareness of the stimulus,
      whereas a later face-specific effect with the same topographic distribution (500-
      to 700-msec poststimulus) was only seen for accurate behavioral discrimination of
      the stimulus content. The present findings suggest a multistage process of object
      category processing, with only the later phase being associated with explicit
      visual awareness. 

PMID- 23859645
TI  - Perceptual sequence learning is more severely impaired than motor sequence
      learning in patients with chronic cerebellar stroke.
AB  - Patients with cerebellar stroke are impaired in procedural learning. Several
      different learning mechanisms contribute to procedural learning in healthy
      individuals. The aim was to compare the relative share of different learning
      mechanisms in patients and healthy controls. Ten patients with cerebellar stroke
      and 12 healthy controls practiced a visuomotor serial reaction time task.
      Learning blocks with high stimulus-response compatibility were exercised
      repeatedly; in between these, participants performed test blocks with the same or
      a different (mirror-inverted or unrelated) stimulus sequence and/or the same or a
      different (mirror-inverted) stimulus-response allocation. This design allowed to
      measure the impact of motor learning and perceptual learning independently and to
      separate both mechanisms from the learning of stimulus-response pairs. Analysis
      of the learning blocks showed that, as expected, both patients and controls
      improved their performance over time, although patients remained significantly
      slower. Analysis of the test blocks revealed that controls showed significant
      motor learning as well as significant visual perceptual learning, whereas
      cerebellar patients showed only significant motor learning. Healthy participants
      were able to use perceptual information for procedural learning even when the
      rule linking stimuli and responses had been changed, whereas patients with
      cerebellar lesions could not recruit this perception-based mechanism. Therefore,
      the cerebellum appears involved in the accurate processing of perceptual
      information independent from prelearned stimulus-response mappings. 

PMID- 23859646
TI  - Going beyond inferior prefrontal involvement in semantic control: evidence for
      the additional contribution of dorsal angular gyrus and posterior middle temporal
      cortex.
AB  - Semantic cognition requires a combination of semantic representations and
      executive control processes to direct activation in a task- and time-appropriate
      fashion [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke
      aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132
      2147, 2006]. We undertook a formal meta-analysis to investigate which regions
      within the large-scale semantic network are specifically associated with the
      executive component of semantic cognition. Previous studies have described in
      detail the role of left ventral pFC in semantic regulation. We examined 53
      studies that contrasted semantic tasks with high > low executive requirements to
      determine whether cortical regions beyond the left pFC show the same response
      profile to executive semantic demands. Our findings revealed that right pFC,
      posterior middle temporal gyrus (pMTG) and dorsal angular gyrus (bordering
      intraparietal sulcus) were also consistently recruited by executively demanding
      semantic tasks, demonstrating patterns of activation that were highly similar to
      the left ventral pFC. These regions overlap with the lesions in aphasic patients
      who exhibit multimodal semantic impairment because of impaired regulatory control
      (semantic aphasia)-providing important convergence between functional
      neuroimaging and neuropsychological studies of semantic cognition. Activation in
      dorsal angular gyrus and left ventral pFC was consistent across all types of
      executive semantic manipulation, regardless of whether the task was receptive or
      expressive, whereas pMTG activation was only observed for manipulation of control
      demands within receptive tasks. Second, we contrasted executively demanding tasks
      tapping semantics and phonology. Our findings revealed substantial overlap
      between the two sets of contrasts within left ventral pFC, suggesting this region
      underpins domain-general control mechanisms. In contrast, we observed relative
      specialization for semantic control within pMTG as well as the most ventral
      aspects of left pFC (BA 47), consistent with our proposal of a distributed
      network underpinning semantic control. 

PMID- 23859647
TI  - Neural and psychological maturation of decision-making in adolescence and young
      adulthood.
AB  - We examined the maturation of decision-making from early adolescence to mid
      adulthood using fMRI of a variant of the Iowa gambling task. We have previously
      shown that performance in this task relies on sensitivity to accumulating
      negative outcomes in ventromedial PFC and dorsolateral PFC. Here, we further
      formalize outcome evaluation (as driven by prediction errors [PE], using a
      reinforcement learning model) and examine its development. Task performance
      improved significantly during adolescence, stabilizing in adulthood. Performance
      relied on greater impact of negative compared with positive PEs, the relative
      impact of which matured from adolescence into adulthood. Adolescents also showed
      increased exploratory behavior, expressed as a propensity to shift responding
      between options independently of outcome quality, whereas adults showed no
      systematic shifting patterns. The correlation between PE representation and
      improved performance strengthened with age for activation in ventral and dorsal
      PFC, ventral striatum, and temporal and parietal cortices. There was a medial
      lateral distinction in the prefrontal substrates of effective PE utilization
      between adults and adolescents: Increased utilization of negative PEs, a hallmark
      of successful performance in the task, was associated with increased activation
      in ventromedial PFC in adults, but decreased activation in ventrolateral PFC and
      striatum in adolescents. These results suggest that adults and adolescents engage
      qualitatively distinct neural and psychological processes during decision-making,
      the development of which is not exclusively dependent on reward-processing
      maturation. 

PMID- 23859648
TI  - What evidence supports special processing for faces? A cautionary tale for fMRI
      interpretation.
AB  - We trained a neurocomputational model on six categories of photographic images
      that were used in a previous fMRI study of object and face processing.
      Multivariate pattern analyses of the activations elicited in the object-encoding
      layer of the model yielded results consistent with two previous, contradictory
      fMRI studies. Findings from one of the studies [Haxby, J. V., Gobbini, M. I.,
      Furey, M. L., Ishai, A., Schouten, J. L., & Pietrini, P. Distributed and
      overlapping representations of faces and objects in ventral temporal cortex.
      Science, 293, 2425-2430, 2001] were interpreted as evidence for the object-form
      topography model. Findings from the other study [Spiridon, M., & Kanwisher, N.
      How distributed is visual category information in human occipito-temporal cortex?
      An fMRI study. Neuron, 35, 1157-1165, 2002] were interpreted as evidence for
      neural processing mechanisms in the fusiform face area that are specialized for
      faces. Because the model contains no special processing mechanism or specialized
      architecture for faces and yet it can reproduce the fMRI findings used to support
      the claim that there are specialized face-processing neurons, we argue that these
      fMRI results do not actually support that claim. Results from our
      neurocomputational model therefore constitute a cautionary tale for the
      interpretation of fMRI data. 

PMID- 23859649
TI  - Development of risk taking: contributions from adolescent testosterone and the
      orbito-frontal cortex.
AB  - The role of puberty in the development of risk taking remains poorly understood.
      Here, in a normative sample of 268 participants between 8 and 25 years old, we
      applied a psycho-endocrine neuroimaging approach to investigate the contribution
      of testosterone levels and OFC morphology to individual differences in risk
      taking. Risk taking was measured with the balloon analogue risk-taking task. We
      found that, corrected for age, higher endogenous testosterone level was related
      to increased risk taking in boys (more explosions) and girls (more money earned).
      In addition, a smaller medial OFC volume in boys and larger OFC surface area in
      girls related to more risk taking. A mediation analysis indicated that OFC
      morphology partly mediates the association between testosterone level and risk
      taking, independent of age. Mediation was found in such a way that a smaller
      medial OFC in boys potentiates the association between testosterone and risk
      taking but suppresses the association in girls. This study provides insights into
      endocrinological and neural underpinnings of normative development of risk
      taking, by indicating that OFC morphology, at least partly, mediates the
      association between testosterone and risk-taking behavior. 

PMID- 23859651
TI  - Recent advances in robotic surgery in female urology.
AB  - Pelvic organ prolapse and lower urinary tract fistulas are two disorders
      frequently managed in female urology. New techniques have been adapted and
      improved to decrease morbidity and improve clinical outcomes of these disorders.
      The adaptation of minimally-invasive approaches for the management of pelvic
      organ prolapse and lower urinary tract fistulas began with laparoscopy. However,
      laparoscopic surgery has not gained widespread popularity as a result of the
      associated technical challenges, such as intracorporeal suturing and pelvic
      dissection. Robotic surgery has been widely carried out in urological oncology
      since 2001, and has been widely adapted because of its advantages over
      conventional laparoscopy for the management of pelvic organ prolapse and lower
      urinary tract fistulas. The current literature has shown the safety, feasibility
      and favorable clinical outcomes of robotic surgery for the treatment of these
      disorders. Robotic surgery in the management of pelvic organ prolapse and lower
      urinary tract fistula repairs might offer a promising advancement and benefits.
      However, further long-term data should be followed to assess the durability of
      this newer, and minimally-invasive approach. 

PMID- 23859650
TI  - Rejection sensitivity polarizes striatal-medial prefrontal activity when
      anticipating social feedback.
AB  - As a social species, humans are acutely aware of cues that signal inclusionary
      status. This study characterizes behavioral and neural responses when individuals
      anticipate social feedback. Across two fMRI studies, participants (n = 42) made
      social judgments about supposed peers and then received feedback from those
      individuals. Of particular interest was the neural activity occurring when
      participants were awaiting social feedback. During this anticipatory period,
      increased neural activity was observed in the ventral striatum, a central
      component of the brain's reward circuitry, and dorsomedial pFC, a brain region
      implicated in mentalizing about others. Individuals high in rejection sensitivity
      exhibited greater responses in both the ventral striatum and dorsomedial pFC when
      anticipating positive feedback. These findings provide initial insight into the
      neural mechanisms involved in anticipating social evaluations as well as the
      cognitive processes that underlie rejection sensitivity. 

PMID- 23859652
TI  - Institutional point-of-care glucometer identifies population trends in blood
      glucose associated with war.
AB  - BACKGROUND: Acute physiological stress has been shown to impair glucose
      homeostasis. War is a period of acute psychological stress, and its effect on
      glucose control is unknown. In this study random point-of-care (POC) glucose
      levels were measured using an automated, institutional glucometer in hospitalized
      adult patients prior to versus during the Israeli Pillar of Defense campaign
      (November 7-10, 2012). SUBJECTS AND METHODS: Random POC glucose values measured
      with the institutional blood glucose monitoring system were obtained 1 week prior
      to the Pillar of Defense campaign (November 7-10, 2012) and compared with values
      to those obtained during the first 4 days of the war (November 14-17, 2012).
      RESULTS: In total, 3,573 POC glucose measures were included: 1,865 during the pre
      war period and 1,708 during the campaign. POC glucose measures were significantly
      higher during the war compared with the week preceding the war: 9.7+/-4.7 versus
      9.3+/-4.2 mmol/L (P=0.02). In a general linear model, period (pre-war vs. during
      war) persisted as a significant predictor of POC glucose even after controlling
      for age, sex, and department type (internal medicine vs. surgical). CONCLUSIONS:
      Acute stress, such as a wartime situation, is associated with a significant
      increase in random blood glucose values in a population of hospitalized adults.
      Long-term follow-up of the individuals hospitalized during these two periods can
      reveal differences in morbidity and mortality trends.

PMID- 23859653
TI  - Improvement in the prehospital recognition of tension pneumothorax: the effect of
      a change to paramedic guidelines and education.
AB  - INTRODUCTION: An audit of ambulance service clinical records from 2001 to 2002 in
      Melbourne, Australia revealed 10 patients with tension pneumothorax on arrival at
      hospital which had been undetected or untreated by paramedics. The clinical
      practice guideline for paramedic recognition of tension pneumothorax was
      subsequently changed to emphasise heightened clinical suspicion of a tension
      pneumothorax in the setting of chest trauma, especially when patients were
      managed with positive pressure ventilation. This study was undertaken to
      determine whether the number of undetected or untreated tension pneumothoraces
      had decreased after the new clinical practice guideline and associated education
      program; if there were unintended consequences arising from earlier paramedic
      intervention; and what effect, if any, this change had on subsequent hospital
      treatment. METHODS: Retrospective case note review of all patients requiring
      intercostal catheter (ICC) insertion at The Alfred Hospital, Melbourne,
      Australia, using records from Ambulance Victoria, the Alfred Trauma Registry and
      the National Coronial Information System. RESULTS: In 2001-2002 paramedics
      treated 22 patients with suspected tension pneumothorax before transport to the
      Alfred Hospital. In 2006-2007 this number had increased to 81. There was a
      decrease from ten to four in the number of unrecognised or untreated tension
      pneumothoraces between the two time periods. No unintended or adverse
      consequences of prehospital needle decompression could be found. However, there
      was an increase in the number of patients who had prehospital needle
      decompression that needed further treatment for tension pneumothorax on arrival
      at hospital. This need for further treatment was associated with use of shorter
      cannulas and unilateral needle decompression by paramedics. CONCLUSION: A small
      change in clinical practice guidelines, supported by an education and audit
      program, led to a reduction in unrecognised untreated tension pneumothoraces by
      paramedics without an increase in complications. Paramedics should be aware that
      a shorter cannula may fail to reach the pleural space and that both sides of the
      chest may require decompression.

PMID- 23859654
TI  - Cys-leukotrienes promote fibrosis in a mouse model of eosinophil-mediated
      respiratory inflammation.
AB  - Leukotrienes (i.e., products of the 5-lipoxygenase pathway) are thought to be
      contributors to lung pathologies. Moreover, eosinophils have been linked with
      pulmonary leukotriene activities both as potential sources of these mediators and
      as responding effector cells. The objective of the present study was to define
      the role(s) of leukotrienes in the lung pathologies accompanying eosinophil
      associated chronic respiratory inflammation. A transgenic mouse model of chronic
      T helper (Th) 2-driven inflammation expressing IL-5 from T cells and human
      eotaxin-2 locally in the lung (I5/hE2) was used to define potential in vivo
      relationships among eosinophils, leukotrienes, and chronic Th2-polarized
      pulmonary inflammation. Airway levels of cys-leukotrienes and leukotriene B4
      (LTB4) are both significantly elevated in I5/hE2 mice. The eosinophil-mediated
      airway hyperresponsiveness (AHR) characteristic of these mice was abolished in
      the absence of leukotrienes (i.e., 5-lipoxygenase-deficient I5/hE2). More
      importantly, the loss of leukotrienes led to an unexpectedly significant decrease
      in collagen deposition (i.e., pulmonary fibrosis) that accompanied elevated
      levels of IL-4/-13 and TGF-beta in the lungs of I5/hE2 mice. Further studies
      using mice deficient for the LTB4 receptor (BLT-1(-/-)/I5/hE2) and I5/hE2 animals
      administered a cys-leukotriene receptor antagonist (montelukast) demonstrated
      that the AHR and the enhanced pulmonary fibrosis characteristic of the I5/hE2
      model were uniquely cys-leukotriene-mediated events. These data demonstrate that,
      similar to allergen challenge models of wild-type mice, cys-leukotrienes underlie
      AHR in this transgenic model of severe pulmonary Th2 inflammation. These data
      also suggest that an underappreciated link exists among eosinophils, cys
      leukotriene-mediated events, and fibrotic remodeling associated with elevated
      levels of IL-4/-13 and TGF-beta. 

PMID- 23859655
TI  - New interfacial microtubule inhibitors of marine origin, PM050489/PM060184, with
      potent antitumor activity and a distinct mechanism.
AB  - We have investigated the target and mechanism of action of a new family of
      cytotoxic small molecules of marine origin. PM050489 and its dechlorinated
      analogue PM060184 inhibit the growth of relevant cancer cell lines at
      subnanomolar concentrations. We found that they are highly potent microtubule
      inhibitors that impair mitosis with a distinct molecular mechanism. They bind
      with nanomolar affinity to unassembled alphabeta-tubulin dimers, and PM050489
      binding is inhibited by known Vinca domain ligands. NMR TR-NOESY data indicated
      that a hydroxyl-containing analogue, PM060327, binds in an extended conformation,
      and STD results define its binding epitopes. Distinctly from vinblastine, these
      ligands only weakly induce tubulin self-association, in a manner more reminiscent
      of isohomohalichondrin B than of eribulin. PM050489, possibly acting like a hinge
      at the association interface between tubulin heterodimers, reshapes Mg(2+)
      induced 42 S tubulin double rings into smaller 19 S single rings made of 7 +/- 1
      alphabeta-tubulin dimers. PM060184-resistant mutants of Aspergillus nidulans map
      to beta-tubulin Asn100, suggesting a new binding site different from that of
      vinblastine at the associating beta-tubulin end. Inhibition of assembly dynamics
      by a few ligand molecules at the microtubule plus end would explain the antitumor
      activity of these compounds, of which PM060184 is undergoing clinical trials. 

PMID- 23859656
TI  - Microstructural constitutive model of active coronary media.
AB  - Although vascular smooth muscle cells (VSMCs) are pivotal in physiology and
      pathology, there is a lack of detailed morphological data on these cells. The
      objective of this study was to determine dimensions (width and length) and
      orientation of swine coronary VSMCs and to develop a microstructural constitutive
      model of active media. The dimensions, spatial aspect ratio and orientation angle
      of VSMCs measured at zero-stress state were found to follow continuous normal (or
      bimodal normal) distributions. The VSMCs aligned off circumferential direction of
      blood vessels with symmetrical polar angles 18.7 degrees  +/- 10.9 degrees , and
      the local VSMC deformation was affine with tissue-level deformation. A
      microstructure-based active constitutive model was developed to predict the
      biaxial vasoactivity of coronary media, based on experimental measurements of
      geometrical and deformation features of VSMCs. The results revealed that the
      axial active response of blood vessels is associated with multi-axial contraction
      as well as oblique VSMC arrangement. The present morphological database is
      essential for developing accurate structural models and is seminal for
      understanding the biomechanics of muscular vessels.

PMID- 23859658
TI  - Bio-orthogonal and combinatorial approaches for the design of binding growth
      factors.
AB  - Merrifield chemistry enables the convenient synthesis of oligonucleotides and
      peptides, while recombinant DNA technology has facilitated protein engineering.
      Recently, protein engineering has been extended into bio-orthogonal protein
      engineering by the development of specific chemical or enzymatic modification
      technologies. The combinatorial approach of molecular evolutionary engineering
      (or in vitro selection) has also provided a new design tool for functional
      peptides. These methodologies have enabled the development of various new
      proteinaceous materials for biological and medical applications. Here, we will
      discuss recent progress in the molecular design of proteins with respect to the
      preparation of binding growth factors, which are of increasing importance in the
      biomaterials field.

PMID- 23859657
TI  - The eradication of breast cancer cells and stem cells by 8-hydroxyquinoline
      loaded hyaluronan modified mesoporous silica nanoparticle-supported lipid
      bilayers containing docetaxel.
AB  - Breast cancer stem cells (BCSCs), which can fully recapitulate the tumor origin
      and are often resistant to chemotherapy and radiotherapy, are currently
      considered as a major obstacle for breast cancer treatment. To achieve the goal
      of both targeting BCSCs and bulk breast cancer cells, we developed 8
      hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticles (MSN)
      supported lipid bilayers (HA-MSS) and docetaxel-loaded MSS. The results showed
      that the size of all the nanoparticles was smaller than 200 nm. BCSCs were
      enriched from MCF-7 cells by a sphere formation method and identified with the
      CD44(+)/CD24(-) phenotype. Quantitative and qualitative analysis demonstrated
      that HA promotes the uptake of HA-MSS in CD44-overexpressing MCF-7 mammospheres,
      revealing the mechanism of receptor-mediated endocytosis. DTX or DTX-loaded MSS
      showed much enhanced cytotoxicity against MCF-7 cells compared with MCF-7
      mammospheres, whereas 8-HQ or 8-HQ-loaded HA-MSS showed much enhanced
      cytotoxicity against MCF-7 mammospheres compared with MCF-7 cells. In the MCF-7
      xenografts in mice, the combination therapy with DTX-loaded MSS plus 8-HQ-loaded
      HA-MSS produced the strongest antitumor efficacy, with little systemic toxicity
      (reflecting by loss of body weight) in mice. Thus, this combination therapy may
      provide a potential strategy to improve the therapy of breast cancer by
      eradication of breast cancer cells together with BCSCs.

PMID- 23859659
TI  - Mechanisms of monoclonal antibody stabilization and release from silk
      biomaterials.
AB  - The availability of stabilization and sustained delivery systems for antibody
      therapeutics remains a major clinical challenge, despite the growing development
      of antibodies for a wide range of therapeutic applications due to their
      specificity and efficacy. A mechanistic understanding of protein-matrix
      interactions is critical for the development of such systems and is currently
      lacking as a mode to guide the field. We report mechanistic insight to address
      this need by using well-defined matrices based on silk gels, in combination with
      a monoclonal antibody. Variables including antibody loading, matrix density,
      charge interactions, hydrophobicity and water access were assessed to clarify
      mechanisms involved in the release of antibody from the biomaterial matrix. The
      results indicate that antibody release is primarily governed by hydrophobic
      interactions and hydration resistance, which are controlled by silk matrix
      chemistry, peptide domain distribution and protein density. Secondary ionic
      repulsions are also critical in antibody stabilization and release. Matrix
      modification by free methionine incorporation was found to be an effective
      strategy for mitigating encapsulation induced antibody oxidation. Additionally,
      these studies highlight a characterization approach to improve the understanding
      and development of other protein sustained delivery systems, with broad
      applicability to the rapidly developing monoclonal antibody field. 

PMID- 23859660
TI  - Graphene oxide covalently grafted upconversion nanoparticles for combined NIR
      mediated imaging and photothermal/photodynamic cancer therapy.
AB  - Theranostics, the integration of diagnostics and therapies, has become a new
      concept in the battles with various major diseases such as cancer. Here, we
      report a multifunctional nanoplatform, which is developed by covalently grafting
      core-shell structured upconversion nanoparticles (UCNPs) with nanographene oxide
      (NGO) via bifunctional polyethylene glycol (PEG), and then loading phthalocyanine
      (ZnPc) on the surface of NGO. The obtained UCNPs-NGO/ZnPc nanocomposites are not
      only be used as upconversion luminescence (UCL) imaging probes of cells and whole
      body animals with high contrast for diagnosis, but also can generate cytotoxic
      singlet oxygen under light excitation for photodynamic therapy (PDT), as well as
      rapidly and efficiently convert the 808 nm laser energy into thermal energy for
      photothermal therapy (PTT). A remarkably improved and synergistic therapeutic
      effect compared to PTT or PDT alone is obtained, providing high therapeutic
      efficiency for cancer treatment. Therefore, benefiting from the unique
      multifunctional hybrid nanostructure, UCNPs-NGO/ZnPc nanocomposites developed
      herein are promising as an integrated theranostic probe for potential UCL image
      guided combinatorial PDT/PTT of cancer.

PMID- 23859661
TI  - Towards the ICD-11: Initiatives taken by the Japanese Society for Psychiatry and
      Neurology to address needs of patients and clinicians.

PMID- 23859662
TI  - Abortion and subsequent mental health: Review of the literature.
AB  - The risk that abortion may be correlated with subsequent mental disorders needs a
      careful assessment, in order to offer women full information when facing a
      difficult pregnancy. All research papers published between 1995 and 2011, were
      examined, to retrieve those assessing any correlation between abortion and
      subsequent mental problems. A total of 36 studies were retrieved, and six of them
      were excluded for methodological bias. Depression, anxiety disorders (e.g. post
      traumatic stress disorder) and substance abuse disorders were the most studied
      outcome. Abortion versus childbirth: 13 studies showed a clear risk for at least
      one of the reported mental problems in the abortion group versus childbirth, five
      papers showed no difference, in particular if women do not consider their
      experience of fetal loss to be difficult, or if after a fetal reduction the
      desired fetus survives. Only one paper reported a worse mental outcome for
      childbearing. Abortion versus unplanned pregnancies ending with childbirth: four
      studies found a higher risk in the abortion groups and three, no difference.
      Abortion versus miscarriage: three studies showed a greater risk of mental
      disorders due to abortion, four found no difference and two found that short-term
      anxiety and depression were higher in the miscarriage group, while long-term
      anxiety and depression were present only in the abortion group. In conclusion,
      fetal loss seems to expose women to a higher risk for mental disorders than
      childbirth; some studies show that abortion can be considered a more relevant
      risk factor than miscarriage; more research is needed in this field. 

PMID- 23859663
TI  - Atypical antipsychotics in the treatment of delirium.
AB  - The aim of this study was to review the efficacy and safety of atypical
      antipsychotics, comparing within class, placebo, or compared to another active
      treatment for delirium. A literature search was conducted using PubMed, EMBASE,
      and the Cochrane database (1 January 1990-5 November 2012). Selection criteria
      for review were prospective, controlled studies (comparison studies), using
      validated delirium rating scales as outcome measures. A total of six prospective,
      randomized controlled studies were included in the review. It was found that
      atypical antipsychotics are effective and safe in treating delirium, even though
      there seemed to be no difference between each agent. In particular, comparison
      studies with haloperidol showed that the efficacy of atypical antipsychotics was
      similar to that of low-dose haloperidol. It was concluded that atypical
      antipsychotics appear to be effective and tolerable in the management of
      delirium, even though the evidence is limited. 

PMID- 23859664
TI  - Prevalence and patterns of psychiatric disorders in referred adolescents with
      Internet addiction.
AB  - AIM: To investigate prevalence and patterns of psychiatric disorders in young
      subjects with Internet addiction (IA). METHODS: Subjects were taken from a sample
      of patients, aged 10-18 years old, referred to Istanbul Medical Faculty, Child
      and Adolescent Psychiatry Department due to a variety of behavioral and emotional
      problems alongside problematic Internet use. Inclusion criteria included IQ >=70
      and score >=80 on Young's Internet Addiction Scale (YIAS). Psychiatric
      comorbidity was assessed using the Turkish version of the Schedule for Affective
      Disorders and Schizophrenia for School Age Children-Present and Lifetime Version.
      RESULTS: Subjects were 45 boys (75%) and 15 girls (25%) with an age range of 10
      18 years old (mean age, 13.38 +/- 1.79 years). A total of 60% (n = 36) had been
      using Internet for >=5 years. Mean hours/week spent on the Internet was 53.7
      (range, 30-105 h) and the average YIAS score was 85. All subjects (100%) had at
      least one and 88.3% (n = 53) had at least two comorbid psychiatric disorders. The
      frequency of diagnostic groups were as follows: behavioral disorder, n = 52
      (86.7%); anxiety disorder, n = 43 (71.7%); mood disorder, n = 23 (38.3%);
      elimination disorder, n = 16 (26.7%); tic disorder, n = 10 (16.7%); and substance
      use disorder, n = 4 (6.7%). The most common psychiatric disorders were attention
      deficit hyperactivity disorder (n = 53; 83.3%), social phobia (n = 21; 35.0%) and
      major depressive disorder (n = 18; 30.0%). CONCLUSION: High rates of psychiatric
      comorbidity, particularly behavioral, anxiety and mood disorders were found in
      young subjects with IA. Because the presence of psychiatric disorders may affect
      the management /prognosis of IA, assessment should include that for other
      psychiatric disorders.

PMID- 23859665
TI  - Plasma brain-derived neurotrophic factor in earthquake survivors with full and
      partial post-traumatic stress disorder.

PMID- 23859666
TI  - Fluvoxamine and celecoxib may have caused adverse events in an elderly patient.

PMID- 23859667
TI  - Antiretroviral agent entecavir exacerbates major depression.

PMID- 23859668
TI  - Reversible skin rash in a bipolar disorder patient on first use of lithium.

PMID- 23859669
TI  - Classification of intellectual disability using the Wechsler Intelligence Scale
      for Children: Full Scale IQ or General Abilities Index?
AB  - AIM: We examined the implications of using the Full Scale IQ (FSIQ) versus the
      General Abilities Index (GAI) for determination of intellectual disability using
      the Wechsler Intelligence Scales for Children, fourth edition (WISC-IV). METHOD:
      Children referred for neuropsychological assessment (543 males, 290 females; mean
      age 10y 5mo, SD 2y 9mo, range 6-16y) were administered the WISC-IV and the
      Adaptive Behavior Assessment System, second edition (ABAS-II). RESULTS: GAI and
      FSIQ were highly correlated; however, fewer children were identified as having
      intellectual disability using GAI (n=159) than when using FSIQ (n=196). Although
      the 44 children classified as having intellectual disability based upon FSIQ (but
      not GAI) had significantly higher adaptive functioning scores than those meeting
      intellectual disability criteria based upon both FSIQ and GAI, mean adaptive
      scores still fell within the impaired range. FSIQ and GAI were comparable in
      predicting impairments in adaptive functioning. INTERPRETATION: Using GAI rather
      than FSIQ in intellectual disability diagnostic decision-making resulted in fewer
      individuals being diagnosed with intellectual disability; however, the mean GAI
      of the disqualified individuals was at the upper end of criteria for intellectual
      impairment (standard score 75), and these individuals remained adaptively
      impaired. As GAI and FSIQ were similarly predictive of overall adaptive
      functioning, the use of GAI for intellectual disability diagnostic decision
      making may be of limited value.

PMID- 23859670
TI  - The effect of group-adapted motivational interviewing on traffic convictions and
      driving behaviors of court-adjudicated youth.
AB  - OBJECTIVE: To evaluate the effect of a 20 hr prevention program (The Reducing
      Dangerous Driving Program, RYDD) in reducing traffic citation recidivism and high
      risk driving behaviors among 16- to 20-year-olds referred by the Rhode Island
      courts for traffic citation events. METHODS: Participants were randomized to
      receive either the Adapted Group Motivational Interviewing (AGMI) or the
      Community Service (CS) arm of the study. Participants completed a survey at
      baseline and at 6 and 12 months post-RYDD completion. Objective court data on
      post-RYDD traffic event citations were also collected. RESULTS: There were no
      significant differences between the groups on measures of high-risk driving
      behaviors and post-RYDD traffic event citation recidivism at the 12-month follow
      up assessment. CONCLUSIONS: There remains a need to develop and test behavioral
      interventions that could address high-risk driving behaviors and associated motor
      vehicle crash (MVC) risk in this population. Further research is needed to
      determine whether group behavioral interventions that use motivational
      interviewing could be a possible mechanism for changing high-risk behaviors,
      traffic citation recidivism, and the associated risks that these pose for MVCs
      among young drivers.

PMID- 23859671
TI  - Asymmetric effect of oxygen adsorption on electron and hole mobilities in bilayer
      graphene: long- and short-range scattering mechanisms.
AB  - We probe electron and hole mobilities in bilayer graphene under exposure to
      molecular oxygen. We find that the adsorbed oxygen reduces electron mobilities
      and increases hole mobilities in a reversible and activated process. Our
      experimental results indicate that hole mobilities increase due to the screening
      of long-range scatterers by oxygen molecules trapped between the graphene and the
      substrate. First principle calculations show that oxygen molecules induce
      resonant states close to the charge neutrality point. Electron coupling with such
      resonant states reduces the electron mobilities, causing a strong asymmetry
      between electron and hole transport. Our work demonstrates the importance of
      short-range scattering due to adsorbed species in the electronic transport in
      bilayer graphene on SiO2 substrates. 

PMID- 23859672
TI  - Plasma and tissue cefazolin concentrations in obese patients undergoing cesarean
      delivery and receiving differing pre-operative doses of drug.
AB  - BACKGROUND: Patients undergoing cesarean delivery typically receive a 1-g to 2-g
      dose of cefazolin as pre-operative antibacterial prophylaxis. This traditional
      dosage may not provide an adequate tissue concentration of cefazolin in obese
      patients during the peri-operative period. This study compared the tissue
      concentrations of prophylactic cefazolin administered as a either a 2-g or a 4-g
      dose prior to cesarean delivery in obese patients. METHODS: Twenty obese patients
      (first trimester body mass index [BMI] >35) who underwent cesarean delivery
      completed this randomized study. Eleven patients received 2 g of cefazolin, and
      nine received 4 g. Blood and subcutaneous tissues were collected at the times of
      the incision and closure. Myometrial biopsies were collected at uterine closure.
      A cefazolin concentration threshold of 4 mcg/g for tissue samples was used as a
      surrogate adequate concentration. Plasma and tissue cefazolin concentrations were
      compared for the two doses. RESULTS: Mean plasma, umbilical cord, and myometrial
      cefazolin concentrations were significantly higher in the 4-g treatment group
      (p<0.05). Subcutaneous incision site tissue obtained at time of incision creation
      also was significantly higher in the 4-g group than in the 2-g group (40.11+/
      24.10 mcg/g vs. 18.36+/-6.68 mcg/g; p=0.0005). Subcutaneous tissue concentrations
      at closure were significantly different in the two dosage groups (34.89+/-17.42
      mcg/g vs. 21.73+/-16.02 mcg/g; p=0.044). All tissue samples were above the target
      of 4 mcg/g. Body morphometry did not correlate with the variability in cefazolin
      tissue concentration. No surgical site infections, endometritis, or other adverse
      effects were observed. CONCLUSIONS: Administering a prophylactic dose of 4 g of
      cefazolin produced blood and tissue cefazolin concentrations that were
      significantly higher than concentrations obtained from a 2-g dose in patients
      with BMIs between 35 and 60 kg/m(2) undergoing cesarean delivery. It is unclear
      if the larger cefazolin dose produces a more protective anti-infective effect
      than that obtained with the more traditional 2-g dose for cesarean delivery in
      obese patients.

PMID- 23859673
TI  - Prospective, randomized, study of ampicillin-sulbactam versus moxifloxacin
      monotherapy for the treatment of community-acquired complicated intra-abdominal
      infections.
AB  - BACKGROUND: The ideal antimicrobial treatment for intra-abdominal infections
      (IAIs) in the setting of fast-paced emergency departments (EDs) should be
      effective, convenient, and of limited resource utilization. Antibiotic
      monotherapy is a feasible option for this. We conducted a study in which we
      compared two regimens for antibiotic monotherapy recommended by published
      guidelines in ED patients with community-acquired, complicated IAIs (cIAIs).
      METHODS: The study was a prospective, randomized, study of ampicillin-sulbactam
      versus moxifloxacin for cIAIs. After the diagnosis of cIAI was established,
      patients were assigned randomly to receive either moxifloxacin 400 mg
      intravenously (IV) qd followed by moxifloxacin 400 mg orally (PO) qd, or
      ampicillin-sulbactam 1.5 g IV qid followed by ampicillin-sulbactam 750 mg PO
      q12h. Source control procedures were used for all patients and all had complete
      follow-up. The primary efficacy variable for the study was the clinical response
      at the test-of-cure visit. RESULTS: A total of 116 patients were enrolled for
      prospective evaluation and randomized assignment to treatment with ampicillin
      sulbactam (n=55) or moxifloxacin (n=61). At the test-of-cure evaluation, the
      overall clinical failure rate was 13.8%. The clinical failure rates in the
      ampicillin-sulbactam and moxifloxacin groups were 16.4% (9/55) and 11.5% (7/61),
      respectively (p=0.446). With regard to infection site, the clinical failure rate
      in cIAIs consisting of lower gastrointestinal (GI) tract infection was
      significantly lower in the moxifloxacin than in the ampicillin-sulbactam group
      (4.3% vs. 19.6%; p=0.024). According to multivariable analysis, independent risk
      factors for treatment failure were the time to ED presentation >24 h (odds ratio
      [OR] 6.8; 95% CI 1.3-36.2; p=0.024) and ampicillin-sulbactam therapy (OR 9.5; 95%
      CI 1.1-76.6; p=0.033). CONCLUSIONS: A significant difference existed in the
      clinical responses of the two groups. As compared with ampicillin-sulbactam,
      moxifloxacin was more effective for the treatment of community-acquired cIAIs of
      the lower GI tract. A higher risk of treatment failure for antibiotic therapy was
      found for patients presenting to the ED with symptoms of cIAIs lasting >24 h.
      Alternative antimicrobial agents should be considered for treating these
      patients.

PMID- 23859674
TI  - Outbreak of infections caused by Group A Streptococcus after modified radical
      mastectomy.
AB  - BACKGROUND: Eight infections occurred after modified radical mastectomies in a
      tertiary-care hospital. Group A streptococci (GAS) were isolated from three of
      the eight patients. METHODS: To control the outbreak, an epidemiologic
      investigation was conducted, and healthcare workers were screened for pathogens.
      Strains isolated from healthcare workers were compared with patient strains by
      emm typing. RESULTS: One surgeon attended one of the eight operations and
      observed the other seven. Streptococcus strains from the hands of this surgeon
      were identical to the patient strains. After the surgeon was suspended from duty
      and underwent eradication treatment, the outbreak was controlled. CONCLUSIONS:
      This outbreak of GAS infection is believed to have occurred by airborne
      transmission. Suspending patient care by healthcare workers who carry the
      causative GAS in a site(s) other than the respiratory tract for only the first 24
      h they are receiving chemoprophylaxis may not be long enough. Sampling of the
      hands of healthcare workers during an investigation of nosocomial GAS infection
      is valuable.

PMID- 23859675
TI  - The impact of linezolid versus vancomycin on surgical interventions for
      complicated skin and skin structure infections caused by methicillin-resistant
      Staphylococcus aureus.
AB  - BACKGROUND: We conducted a study with the primary objective of assessing whether
      a difference existed in the frequency and type of surgical interventions (SIs)
      implemented in patients treated with linezolid versus vancomycin for the
      management of complicated skin and skin structure infections (cSSSIs) caused by
      methicillin-resistant Staphylococcus aureus (MRSA). METHODS: We analyzed data
      from a phase IV clinical trial evaluating the safety and efficacy of linezolid
      and vancomycin, given for 7-14 d, to treat cSSSIs other than cellulitis that were
      caused by MRSA. The study included patients who received >=1 dose of drug, had a
      cSSSI caused by culture-proved MRSA, and underwent >=1 SI after commencement of
      the study. The types and frequencies of SIs were assessed on a per-patient basis
      during the following three time periods: (1) study days 0-3: the estimated time
      to reach steady-state serum drug concentrations; (2) study days 4-14: the drug
      treatment period (days 4-14) during which steady state drug concentrations are
      likely reached; and (3) study days 15-28: the post-treatment period through end
      of the study (EOS). Independent predictors of >=2 SIs during the drug-treatment
      period were identified by logistic regression. Clinical and microbiologic
      outcomes were assessed at the end of treatment (EOT), and at EOS for the SI
      population. RESULTS: The data analysis included 323 patients (linezolid, n=167;
      vancomycin, n=156). The majority of patients (81% in the linezolid group and 83%
      in the vancomycin group) underwent an initial SI or source control procedure
      within 72 h of study initiation. The most common cSSSIs among patients having SIs
      were abscesses (59%) and infected ulcers (20%). Independent predictors of >=2 SIs
      during study days 4-14 included treatment with vancomycin (OR 5.97; 95% CI 1.97
      18.03), polymicrobial infection (OR 2.84; 95% CI 1.13-7.12), and degree of wound
      induration (OR 1.06; 95% CI 1.02-1.10). Clinical success rates in the SI
      population were 88% in the linezolid group and 80% in the vancomycin group
      (p=0.14) at EOT and 80% in the linezolid group and 68% in the vancomycin group
      (p=0.04) at EOS. Microbiologic success rates were 83% in the linezolid group and
      68% in the vancomycin group (p=0.004) at EOT and 71% in the linezolid group and
      60% in the vancomycin group (p=0.05) at EOS. CONCLUSION: Patients who received
      linezolid had a lower probability of undergoing >=2 SIs during drug treatment.
      Type of antibiotic received was the only modifiable predictor of a greater rate
      of SI during the drug-treatment period. In the patient population of the study,
      with cSSSIs other than cellulitis that were caused by MRSA, and in which at least
      one SI per patient was done within 72 h of the commencement of drug treatment,
      linezolid was associated with a higher rate of clinical success at EOS than was
      vancomycin, as well as with a higher rate of microbiologic success at both EOT
      and EOS.

PMID- 23859676
TI  - Incidence of surgical site infection in colon surgery: comparison with regional,
      national Spanish, and United States standards.
AB  - BACKGROUND: The high prevalence of surgical site infection (SSI) in colon
      surgery, and the clinical and economic impacts of such infections, make its
      monitoring and prevention a priority. METHODS: We conducted a prospective cohort
      study to estimate the rate of SSI in colon surgery and the degree of compliance
      with antibiotic prophylaxis and pre-operative preparation protocols. The study
      population comprised patients who underwent colon surgery at the University
      Hospital of the Alcorcon Foundation in Alcorcon, Spain, from October 2007 to
      December 2009. Risk factors, the observance of antibiotic prophylaxis, and
      compliance with pre-operative preparation protocols were monitored; and their
      influence on SSIs was followed for 30 days after surgery. The main outcome
      measure was comparisons of the rates of SSI in patients undergoing colon surgery
      in Madrid and across the whole of Spain and in the United States, as determined
      in accordance with the surveillance parameters of the National Nosocomial
      Infections Surveillance (NNIS) index. RESULTS: Among a total of 132 patients, we
      found a 10.6% rate of SSI. The indirect standardization rate at our hospital was
      1.75-fold for the United States and 0.64-fold and 0.61-fold, respectively, the
      rates for Madrid and all of Spain. The rates of compliance with antibiotic
      prophylaxis and pre-operative preparation protocols were 93.6% and 56.8%,
      respectively. No relation could be established between these data and the rate of
      infection. The risk factors for SSI found in a multivariable analysis were the
      degree of contamination in surgery and the presence of chronic obstructive
      pulmonary disease (COPD; p<0.05). CONCLUSIONS: The rate of SSI in our study
      population was below that for Madrid and Spain but higher than that for the
      United States. Thorough adherence to the monitoring system was essential for
      obtaining these results.

PMID- 23859677
TI  - Sustained reduction in surgical site infection after abdominal hysterectomy.
AB  - BACKGROUND: During a period of five years, the rate of surgical site infection
      (SSI) after abdominal hysterectomy at our institution was >10%. With the
      implementation of a multifaceted intervention designed to reduce this, the rate
      of SSI fell to <2% in the post-intervention period. The pre- and post
      intervention periods were compared to determine which of the interventions in the
      multifaceted array of interventions was most valuable in decreasing SSI. METHODS:
      A retrospective chart review was done to identify: (1) Parameters associated with
      SSI, and (2) parameters that differed in the pre- and post-intervention periods.
      The intervention included providing departmental SSI rates to the gynecology
      faculty, re-educating operating room (OR) staff personnel about appropriate
      perioperative antibiotic choice and timing, and changing the preferred sterile
      preparation for abdominal surgery from 10% povidone-iodine (PI) to 4%
      chlorhexidine gluconate (CHG). The preliminary results of our review also led to
      the suggestion that surgeons use blood products sparingly, although an absolute
      threshold for transfusion was not specified. RESULTS: Twenty-one of 192 patients
      (10.7%) developed an SSI in the pre-intervention period, whereas 1 of 84 patients
      (1.2%) developed an SSI in the post-intervention period (p=0.006). Surgical site
      infection was associated with obesity (a body mass index [BMI] >=30) (11.5% vs.
      4.8%, p=0.04), receipt of a blood transfusion (18.2% vs. 6.6%, p=0.03), and
      abdominal skin preparation with PI as opposed to CHG (10.1% vs. 2.0%, p=0.07).
      Chlorhexidine gluconate was used more commonly for abdominal skin preparation in
      the post- than in the pre-intervention period (6.6% pre-intervention vs. 50.7%
      post-intervention, p <0.0001). CONCLUSIONS: A multifaceted intervention decreased
      dramatically the rate of SSI after abdominal hysterectomy at our institution. No
      single component of the intervention could be identified as most responsible for
      the improvement.

PMID- 23859678
TI  - The registration of surgical site infections: a comparison of two different
      methods in vascular surgery.
AB  - BACKGROUND: Registration of complications of treatment is an important instrument
      for measuring the quality of health care. Reliable registration depends on
      definitions, the case-finding method that is used, and the registration method
      itself. We conducted a comparative study of two different methods of registration
      for the surveillance of surgical site infections (SSIs) in a single hospital.
      METHODS: The study included all patients in both the surgical database and the
      microbiology and infection-prevention database of the hospital who underwent
      surgery on the abdominal aorta or peripheral vascular procedures from March 1,
      2009 to March 1, 2010. The surgical database included positive scores for SSI in
      cases of positive wound swabs, the need for incision drainage, or the need for
      antibiotic treatment. The microbiology and infection-prevention database used
      criteria from the U.S. Centers for Disease Control and Prevention (CDC), and
      based positive scores on redness, heat, swelling, or pain in the area of a
      surgical incision within 30 d after a procedure, and on a positive swab, drainage
      from an incision, or the presence of pus following a diagnostic puncture.
      RESULTS: The surgical complication database included 218 patients, of whom 20
      (9.2%) had a SSI. The microbiology and infection-prevention database included 236
      patients, of whom 33 (14%) had a SSI. The databases were merged and all
      infections were ascertained by an expert team. The surgical database had a
      sensitivity of 57% for SSIs, whereas the microbiology and infection-prevention
      database had a sensitivity of 93% (p<0.05). CONCLUSION: Physicians provided less
      reliable scores for SSI than did trained infection-control practitioners. This
      raises questions about the comparability of rates of SSI in different
      institutions as a means for judging the quality of hospital care.

PMID- 23859679
TI  - Babesia microti infection presenting as acute splenic laceration.
AB  - BACKGROUND: Blunt abdominal trauma leading to splenic injury can cause
      substantial morbidity, particularly in patients with established splenic
      pathology. In such cases, the extant pathology may increase a patient's
      susceptibility to blunt injury, most notably by inducing hypersplenism; Babesia
      microti may create such a condition. METHODS: Case report and English language
      based literature review. RESULTS: Obtaining an appropriate travel history and
      understanding endemic infectious conditions will better enable the clinician to
      establish readily treatable concomitant diagnoses in the setting of injury.
      CONCLUSIONS: Failure to treat such infections may delay solid organ healing,
      leading to the patient being released to unrestricted and therefore risky
      activity with persistently abnormal splenic architecture.

PMID- 23859680
TI  - Facial necrotizing fasciitis.

PMID- 23859681
TI  - Decolonization strategies to control aerobic gram-negative bacillary infections
      in breast implant surgery.

PMID- 23859682
TI  - Bony erosions secondary to osteotuberculosis of the hand.

PMID- 23859683
TI  - Impact of pre-storage and bedside filtered leukocyte-depleted blood transfusions
      on infective morbidity after colorectal resection: a single-center analysis of
      437 patients.
AB  - BACKGROUND: Leukocyte-depleted blood transfusions were introduced to reduce
      transfusion-associated immunomodulation, but the clinical effects of different
      types of leukocyte depletion have been analyzed rarely. The aim of this survey
      was to analyze the clinical impact of pre-storage leukocyte-depleted blood
      transfusions (considered as pre-storage or bedside-filtered) on post-operative
      complications in patients undergoing elective or urgent colorectal resection.
      METHODS: Data were collected retrospectively from the medical records of 437
      consecutive patients who underwent colorectal resection from 2005 to 2010. All
      patients requiring transfusion received pre-storage or bedside-filtered leukocyte
      depleted red blood cell concentrates according to availability at the blood bank.
      The outcomes were measured by the analysis of post-operative morbidity in
      patients receiving the different types of transfusions or having other
      potentially predictive risk factors. RESULTS: The overall morbidity rate,
      infective morbidity rate, and non-infective morbidity rate were, respectively,
      35.6%, 28.1%, and 21.0%. Two hundred five patients (46.9%) received peri
      operative transfusions. On multivariable analysis, leukocyte-depleted transfusion
      (odds ratio [OR] 3.33; 95% confidence interval [CI] 2.14-5.20; p<0.001) and both
      pre-storage (OR 2.82; 95% CI 1.73-4.59; p<0.001) and bedside-filtered (OR 4.69;
      95% CI 2.54-8.67; p<0.001) transfusions were independent factors for post
      operative morbidity. Prolonged operation (p=0.035), American Society of
      Anesthesiologists score>=3 points (p=0.023), diagnosis of cancer rather than
      benign disease (p=0.022), and urgent operation (p=0.020) were other independent
      predictors of post-operative complications. Patients transfused with bedside
      filtered blood showed significantly higher rates of infective complications
      (51.4% vs. 31.8%; p=0.006), but not non-infectious complications (35.7% vs. 32.6;
      p=0.654) than patients who received pre-storage transfusions. CONCLUSIONS:
      Leukocyte-depleted blood transfusions and, in particular, bedside-filtered blood
      have a significant negative effect on infectious complications after colorectal
      resection.

PMID- 23859684
TI  - Surveillance of bacterial colonization in operating rooms.
AB  - BACKGROUND: Surgical site infections (SSIs) continue to occur at an unacceptably
      high rate, incurring direct costs of up to $10 billion per year in the United
      States and far more than that in total economic costs. There is a continued need
      to identify potential sources of microbial contamination that lead to surgical
      infections. METHODS: Using contact culture plates, we randomly took a total of
      517 samples of various surfaces in 33 operating rooms (ORs) over a 6-mo period.
      RESULTS: Flat surfaces treated with decontamination techniques (floors,
      anesthesia carts, operating tables, and other flat surfaces) grew small numbers
      of bacterial colonies, as did other surfaces that were decontaminated less often.
      Personal items, especially the tops of shoes and personal hats, had much higher
      contamination than the surfaces just described, which in the case of these two
      items averaged 50-60 CFU/20 cm(2). The outsides of face masks contained slightly
      more organisms than did floors, but the insides had almost 100 times more
      organisms, which was of concern because of high leakage rates at the mask-face
      interface. CONCLUSIONS: The culture system used in our study can be used as a
      simplified and cost-effective method of identifying the comparative densities of
      organisms on different surfaces for surveillance of microbial contamination in
      the OR. To reduce bacterial contamination, shoe covers and disposable hair
      coverings should be worn at every operation in which there are substantial risks
      of SSI. Masks that reduce leakage at the mask-face interface should be worn and
      discarded after each operation.

PMID- 23859685
TI  - Outpatient antibiotic use and the incidence of acute appendicitis in Finland: a
      nationwide study from 1990-2008.
AB  - BACKGROUND: The incidence of acute appendicitis (AA) has decreased in Finland. We
      hypothesized that changing trends in outpatient antibiotic use might explain at
      least part of this declining incidence of AA. METHODS: The number of all patients
      with AA in Finland was extracted from the national data base from 1990 to 2008.
      For comparison, the incidence of acute diverticulitis of the colon (AD) was also
      recorded. All outpatient prescriptions of antibiotics belonging to the major
      groups of these drugs were also recorded. We used unit root and co-integration
      analyses for statistical analysis of the data in the study. RESULTS: The
      incidence of AA in Finland declined from 14.5 to 9.8 per 10,000 inhabitants (32%)
      and the incidence of AD increased by 47% between 1993 and 2007. The total
      outpatient use of antibiotics did not increase during this same period, but the
      use of antibiotics effective widely against colonic pathogens (macrolides,
      fluoroquinolones, and cephalosporins) increased significantly. No correlation was
      found between the incidence of AA, that of AD, and the use of different groups of
      antibiotics. CONCLUSIONS: Our nationwide registry study indicated that changes in
      outpatient antibiotic use do not explain the decreasing trend in AA in Finland.
      Other factors, such as improved diagnosis of AA, may have some role in the
      decreasing incidence of AA.

PMID- 23859686
TI  - Perinephric abscess due to Achromobacter xylosoxidans following de-roofing of
      renal cyst.

PMID- 23859687
TI  - Emphysematous cholecystitis.

PMID- 23859688
TI  - Contained cecal perforation within a strangulated scrotal hernia.

PMID- 23859689
TI  - Thoracic vertebral osteomyelitis caused by Burkholderia cepacia in an
      immunocompetent adult.

PMID- 23859690
TI  - Extrahepatic primary adrenal alveolar echinococcosis: a review.
AB  - BACKGROUND: Primary echinococcosis, and especially primary alveolar
      echinococcosis (AE) is rare among adrenal lesions. METHODS: We report a case of
      primary AE in a 28-year-old male with low backache and occasional upper limb pain
      lasting for six months, and review the pertinent but sparse literature on this
      disorder. RESULTS: Evaluation of the patient revealed an abdominal mass as right
      adrenal AE. The adrenal gland is a rare extrahepatic site of occurrence of
      echinococcosis, and particularly of AE. Patients with adrenal echinococcosis
      usually have nonspecific clinical symptoms. Imaging examinations revealed clearly
      the features of AE and its surrounding pathology. Alveolar echinococcosis was
      seen as an inhomogeneous pseudotumor with irregular boundaries, an irregular
      central pseudocystic appearance, and infiltration into surrounding structures. On
      contrast-enhanced computed tomography, the periphery of the mass in AE may be
      enhanced and multicentric vesicles may be seen. Magnetic resonance imaging may
      show the multivesicular morphology of lesions. The definitive diagnosis of AE
      should be confirmed by pathologic or serologic examination. Radical surgical
      resection of the removable parasitic lesion, followed by anti-infective therapy
      with benzimidazoles, is the primary method for treating AE. CONCLUSION: Although
      primary adrenal AE is rare, it should be included in the differential diagnosis
      of adrenal masses, especially in regions where AE is endemic.

PMID- 23859691
TI  - Hemoptysis as an early symptom of abdominal actinomycosis with thoracic extension
      ten years after cholecystectomy with retained gallstone.
AB  - BACKGROUND: Thoracoabdominal actinomycosis is rare, especially in the context of
      readily available medical facilities. METHODS: Case report and review of the
      literature. CASE REPORT: A 54-year-old male patient was admitted because of
      hemoptysis and a pulmonary infiltrate in the left lower lobe. His history was
      unremarkable except for chronic gastritis and an elective laparoscopic
      cholecystectomy performed 10 years earlier. Following persistent hemoptysis,
      elevated inflammatory markers, and a non-revealing bronchoscopy, a computed
      tomography scan of the thorax and upper abdomen revealed a tumor in the upper
      part of the left kidney spreading directly to the adjacent diaphragm and left
      lower lobe. Laparotomy revealed a granulomatous mass containing a gallstone, as
      well as orange granular content. The treatment involved surgical removal of the
      mass, splenectomy, excision of the infiltrated part of the left hemidiaphragm,
      and decortication of the left lower lobe. Because of a prolonged post-operative
      low-grade fever and radiologically confirmed encapsulation in the lingula, the
      patient was given ceftriaxone. Repeat bronchoscopy revealed Actinomyces meyeri.
      The initial antibiotic therapy was replaced with amoxicillin-clavulanic acid,
      after which the patient's health improved. CONCLUSION: Actinomycosis is still a
      highly intriguing disease, as initial symptoms often mislead clinicians. It is
      important to consider the disease whenever we are challenged diagnostically or
      when risk factors are present.

PMID- 23859692
TI  - Self-assembling peptides improve the stability of glucagon-like peptide-1 by
      forming a stable and sustained complex.
AB  - The multiple physiological characterizations of glucagon-like peptide-1 (GLP-1)
      make it a promising drug candidate for the treatment of T2DM. However, the short
      half-life of GLP-1 limits its clinical utility. Self-assembling peptides are
      presumed to wrap GLP-1 peptide, and this helps to prolong the stability of GLP-1
      consequently. The aim of this study was to investigate whether self-assembling
      peptides could be applied to prolong the half-life of GLP-1 as sustained release
      preparations. In this study, five different self-assembling peptides were
      employed. The formation of the complexes was monitored using gel filtration and
      mass spectrometry and was simulated by Molecular Dynamics. Stabilization, insulin
      secretion stimulation, and glucose tolerance tests were performed to investigate
      the physiological characteristics retained by GLP-1 following complex formation
      with self-assembling peptides. Our findings revealed that, among the five
      different self-assembling peptides tested, complex of Pep-1 and GLP-1 exhibited a
      remarkable extension in the half-life of GLP-1. In addition, the experimental
      animals treated with a GLP-1/Pep-1 complex exhibited better blood glucose
      clearance activity over a greater duration of time than the animals treated with
      GLP-1 alone. Based on our results, an adjustment of the Pep-1 and GLP-1 ratios is
      presumed to be able to control the half-life of GLP-1 (e.g., medium-acting and
      long-acting). Collectively, the findings in this study suggest that the self
      assembling peptide Pep-1 could serve as a powerful drug preparation tool to
      extend the short half-life of therapeutic peptides. 

PMID- 23859693
TI  - Predictors of antenatal alcohol use among Australian women: a prospective cohort
      study.
AB  - OBJECTIVE: To identify predictors of antenatal alcohol consumption among women
      who usually consume alcohol. DESIGN: Prospective cohort study. SETTING:
      Australian Longitudinal Study on Women's Health (ALSWH). POPULATION OR SAMPLE: A
      total of 1969 women sampled from the ALSWH 1973-78 cohort. METHODS: Women were
      included if they were pregnant in 2000, 2003, 2006 or 2009. The relationship
      between antenatal alcohol consumption and sociodemographics, reproductive health,
      mental health, physical health, health behaviours, alcohol guidelines and
      healthcare factors was investigated using a multivariate logistic regression
      model. MAIN OUTCOME MEASURES: Alcohol use during pregnancy. RESULTS: Most (82.0%)
      women continued to drink alcohol during pregnancy. Women were more likely to
      drink alcohol during pregnancy if they had consumed alcohol on a weekly basis
      before pregnancy (odds ratio [OR] 1.47; 95% confidence interval [95% CI] 1.13
      1.90), binge drank before pregnancy (OR 2.28; 95% CI 1.76-2.94), or if they were
      pregnant while alcohol guidelines recommended low alcohol versus abstinence (OR
      1.60; 95% CI 1.26-2.03). Drinking during pregnancy was less likely if women had a
      Health Care Card (OR 0.63; 95% CI 0.45-0.88) or if they had ever had fertility
      problems (OR 0.64; 95% CI 0.48-0.86). CONCLUSIONS: Most Australian women who
      drank alcohol continued to do so during pregnancy. Prepregnancy alcohol
      consumption was one of the main predictors of antenatal alcohol use. Alcohol
      guidelines, fertility problems and Health Care Card status also impacted
      antenatal alcohol consumption.

PMID- 23859694
TI  - A diruthenium complex of a "Nindigo" ligand.
AB  - The compound {(MU-Nindigo)[Ru(acac)2]2} = 1, H2(Nindigo) = indigo-N,N'
      diphenylimine and acac(-) = 2,4-pentanedionate, has been structurally
      characterized in the rac form, which exhibits two edge-sharing six-membered
      chelate rings involving ruthenium, and the former beta-diketiminato functions
      with a twist angle of 33.9 degrees  around the central C-C bond. The metric
      parameters suggest a neutral pi acceptor bridge containing coupled s-trans
      configurated alpha-diimines, which are coordinated by two ruthenium(II) centers.
      DFT calculations confirm the experimental structure and oxidation state
      assignment of the rac form; both diastereoisomers are present in solution
      according to (1)H NMR spectroscopy. A very intense long-wavelength MLCT
      absorption at 630 nm (epsilon = 66 800 M(-1) cm(-1)) and a weaker near-IR band at
      1120 nm (epsilon = 3000 M(-1) cm(-1)) are observed for the CH3CN solution.
      Reversible one-electron reduction and oxidation steps were studied by cyclic
      voltammetry, differential pulse voltammetry, EPR, and UV-vis-NIR
      spectroelectrochemistry to exhibit metal-centered oxidation and mixed
      metal/ligand-centered reduction. These results are supported by TD-DFT
      calculations of the species rac- or meso-1(n), n = 3+, 2+, +, 0, -, 2-. 

PMID- 23859695
TI  - Current opinion on 3-[2-[(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-
      4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid, an investigational drug
      targeting caspases and caspase-like proteases: the clinical trials in sight and
      recent anti-inflammatory advances.
AB  - Caspases, or cysteinyl-aspartate specific proteases, are major contributing
      enzymes in inflammation. Caspases are highly specific cysteine proteases closely
      involved in inflammatory responses that are associated with programmed cell
      death, or apoptosis. Inappropriate regulation of cell death, therefore,
      substantially results in a wide array of diseases including, but not limiting to,
      neurodegenerative disorders, ischemic disorders, and cancer. The key molecular
      genes that control cell death are those cell death effectors (pro-apoptosis) of
      the caspase family, on one hand, and the cell death inhibitors (anti-apoptosis)
      of the Bcl-2 family, on the other hand. This unequivocal and unprecedented
      equilibrium between caspases and Bcl-2-related molecules essentially controls
      cells' final demise. Caspases and related proteases are potential therapeutic
      targets in a variety of acute and chronic diseases. Current design of
      biologically active molecules in recent technology is dependent on DNA-based
      scanning of the genome to engineer a variety of molecules such as apoptosis
      inhibitors, caspase regulators and caspase activators, and cytokines involved in
      caspase signaling. This synopsis aims to review relevant patents and to unravel
      the discovery of small-molecule caspase protease inhibitors and their clinical
      ramifications, and further sheds light on recent experimental and clinical
      trials, emphasizing a small molecule dubbed 3-[2-[(2- tert-butyl
      phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)
      pentanoic acid (IDN- 6556/PF-03491390). Current opinion on investigational drugs
      targeting caspases and caspase-like proteases bears the significance of
      understanding the mechanisms of alleviating inflammatory-related acute and
      chronic conditions and their biomedical applications and repercussions.

PMID- 23859696
TI  - Randomized trial of nicotine replacement therapy (NRT), bupropion and NRT plus
      bupropion for smoking cessation: effectiveness in clinical practice.
AB  - BACKGROUND AND AIMS: Bupropion was introduced for smoking cessation following a
      pivotal trial showing that it gave improved efficacy over the nicotine patch and
      also suggesting combination treatment was beneficial. We tested in clinical
      practice for an effectiveness difference between bupropion and nicotine
      replacement therapy (NRT), whether the combination improves effectiveness and
      whether either treatment might be more beneficial for certain subgroups of
      smokers. DESIGN: Open-label randomized controlled trial with 6-month follow-up.
      SETTING: Four UK National Health Service (NHS) smoking cessation clinics.
      PARTICIPANTS: Smokers (n = 1071) received seven weekly behavioural support
      sessions and were randomized to an NRT product of their choice (n = 418),
      bupropion (n = 409) or NRT plus bupropion (n = 244). MEASURES: The primary
      outcome was self-reported cessation over 6 months, with biochemical verification
      at 1 and 6 months. Also measured were baseline demographics, health history,
      smoking characteristics and unwanted events during treatment. FINDINGS:
      Abstinence rates for bupropion (27.9%) and NRT (24.2%) were not significantly
      different (odds ratio = 1.21, 95% confidence interval = 0.883-1.67), and the
      combination rate (24.2%) was similar to that for either treatment alone. There
      was some evidence that the relative effectiveness of bupropion and NRT differed
      according to depression (chi(2) = 2.86, P = 0.091), with bupropion appearing more
      beneficial than NRT in those with a history of depression (29.8 versus 18.5%).
      Several unwanted symptoms were more common with bupropion. CONCLUSION: There is
      no difference in smoking cessation effectiveness among bupropion, nicotine
      replacement therapy and their combination when used with behavioural support in
      clinical practice. There is some evidence that bupropion is more beneficial than
      nicotine replacement therapy for smokers with a history of depression.

PMID- 23859697
TI  - Interleukin-6 and lung inflammation: evidence for a causative role in inducing
      respiratory system resistance increments.
AB  - Interleukin-6 is a multifunctional cytokine that has been shown to be increased
      in some pathological conditions involving the respiratory system such as those
      experimentally induced in animals or spontaneously occurring in humans.
      Experimental data demonstrating that interleukin-6 plays a significant role in
      commonly occurring respiratory system inflammatory diseases are reviewed here.
      Those diseases, i.e. asthma and chronic obstructive pulmonary disease, are
      characterised by mechanical derangements of the respiratory system, for the most
      part due to increased elastance and airway resistance. Recent findings showing
      that interleukin-6 has a causative role in determining an increase in airway
      resistance are reviewed. The end-inflation occlusion method was used to study the
      mechanical properties of the respiratory system before and after interleukin-6
      administration. The cytokine was shown to induce significant, dose-dependent
      increments in both the resistive pressure dissipation due to frictional forces
      opposing the airflow in the airway (ohmic resistance) and the additional
      resistive pressure dissipation due to the visco-elastic properties of the system,
      i.e. stress relaxation (visco-elastic resistance). There were no alterations in
      respiratory system elastance. Even when administered to healthy mammals,
      interleukin-6 determines a significant effect on respiratory system resistance
      causing an increase in the mechanical work of breathing during inspiration. IL-6
      hypothetically plays an active role in the pathogenesis of respiratory system
      diseases and the mechanisms that may be involved are discussed here. 

PMID- 23859698
TI  - Bioadhesive polymers: novel tool for drug delivery.
AB  - Mucoadhesive drug delivery systems came into picture in the early 1980s and are
      one of the most studied novel delivery systems. Several researchers have focused
      on the investigations of the interfacial phenomena of mucoadhesion with the
      mucus. Mucoadhesion can be defined as a state in which two components, of which
      one is of biological origin, are held together for an extended period of time by
      the help of interfacial forces. A number of polymers have shown characteristics
      of bioadhesion and have been used in the formulation of various conventional and
      novel drug delivery systems. Studies demonstrated that these carriers not only
      increase the local therapeutic activity, but also increase the systemic
      availability of the drugs by increasing the residence time at the site of
      application. The current review is an attempt to throw some light on the basics
      of the mucoadhesion: the mechanism of bioadhesion and the polymers that are used
      in the design of the bioadhesive delivery system with their properties that
      affect the bioadhesion.

PMID- 23859700
TI  - Sialolith of a minor salivary gland.

PMID- 23859701
TI  - It's more than you know.

PMID- 23859702
TI  - Comparison of premedication with buprenorphine or methadone with meloxicam for
      postoperative analgesia in dogs undergoing orthopaedic surgery.
AB  - OBJECTIVES: To determine whether methadone, administered before orthopaedic
      surgery, results in improved postoperative analgesia compared to buprenorphine.
      METHODS: Thirty-eight dogs undergoing orthopaedic surgeries (the majority being
      tibial tuberosity advancement or elbow arthrotomy) were premedicated with 0 . 03
      mg/kg acepromazine and either 20 ug/kg buprenorphine or 0 . 5 mg/kg methadone,
      intramuscularly, allocated randomly. Anaesthesia was induced with propofol
      intravenously to effect and maintained with isoflurane in oxygen. 0 . 2 mg/kg
      meloxicam was administered at anaesthetic induction. Sedation was assessed by
      means of a dynamic interactive visual analogue and simple descriptive scales and
      pain by dynamic interactive visual analogue and the short form Glasgow composite
      pain scales, by a single observer blinded to treatment group at intervals for 8
      hours following premedication. RESULTS: Sedation scores were higher than baseline
      in both groups following premedication until the end of the assessment period (P
      = 0 . 0001), with no differences between groups. Pain scores were lower overall
      in dogs premedicated with methadone (dynamic interactive visual analogue scale P
      = 0 . 048; short form Glasgow composite pain scale P = 0 . 0045), and these dogs
      required less additional analgesia (42%, compared to 79% premedicated with
      buprenorphine, P = 0 . 045). CLINICAL SIGNIFICANCE: At the doses investigated,
      methadone produced superior analgesia to buprenorphine for 8 hours
      postoperatively in dogs undergoing orthopaedic surgery.

PMID- 23859703
TI  - Preparation and characterization of self-assembled chitosan nanoparticles for the
      sustained delivery of streptokinase: an in vivo study.
AB  - Chitosan (CS) nanoparticles have been extensively studied as carriers for
      therapeutic proteins in recent years. In this study, streptokinase loaded-CS
      nanoparticles were prepared and the pharmacokinetic parameters of streptokinase
      were compared with those of naked streptokinase. The preparation method included
      stirring the protein with the CS solution. The optimized combination was used for
      animal experiments to determine the streptokinase activity in rat plasma. Blood
      samples were collected at specified intervals and the activity assay was
      performed based on amidolysis activity of the chromogenic substrate, S2251, by
      streptokinase-plasminogen activator complex. The results demonstrated that
      streptokinase-loaded CS nanoparticles have more prolonged amidolytic activity in
      vivo compared to the naked one.

PMID- 23859704
TI  - Epigenetic therapy in non-small-cell lung cancer: targeting DNA
      methyltransferases and histone deacetylases.
AB  - INTRODUCTION: Epigenetics refers to heritable modifications of DNA and associated
      chromatin components that influence gene expression without altering DNA coding
      sequence. Epigenetic dysregulation is a central contributor to oncogenesis and is
      increasingly a focus of interest in cancer therapeutic research. Two key levels
      of aberrant epigenetic control are DNA methylation and histone acetylation.
      Primary regulators of these epigenetic changes include DNA methyltransferases
      (DNMTs) and histone deacetylases (HDACs). AREAS COVERED: This review focuses on
      epigenetic changes in non-small-cell lung cancer and recent preclinical and
      clinical studies targeting these changes. DNMT inhibitors were previously
      explored at or near maximally tolerated doses, levels at which these agents are
      cytotoxic but have suboptimal effects on DNA methylation. Use of these inhibitors
      at substantially lower doses, in combination with HDAC inhibitors, can promote re
      expression of silenced tumor suppressor genes, can result in major clinical
      responses and may alter tumor responsiveness to subsequent cytotoxic therapies.
      EXPERT OPINION: Combinatorial epigenetic therapy has demonstrated encouraging
      clinical activity, but many relevant questions remain. Global strategies
      influencing the epigenome may have both positive and potential negative long-term
      effects on cancer progression. Further clinical investigation of this approach,
      including exploratory studies to define predictive biomarkers, is warranted.

PMID- 23859705
TI  - Women's ability to self-screen for contraindications to combined oral
      contraceptive pills in Tanzanian drug shops.
AB  - OBJECTIVE: To estimate the accuracy of self-screening for contraindications to
      combined oral contraceptive pills (COCs) and to estimate the proportion of women
      with contraindications to hormonal methods among those using drug shops in
      Tanzania. METHODS: Trained nurses interviewed 1651 women aged 18-39 years who
      self-screened for contraindications to COCs with the help of a poster at drug
      shops in Tanzania. Nurse assessment of the women served as the gold standard for
      comparison with self-assessment. Blood pressure was also measured onsite.
      RESULTS: Nurses reported that 437 (26.5%) women were not eligible to use COCs,
      compared with 485 (29.4%) according to self-report. Overall, 133 (8.1%) women who
      said that they were eligible were deemed ineligible by nurses. The rate of
      ineligibility was artificially high owing to participant and nurse assessments
      that were incorrectly based on adverse effects of pill use and cultural reasons,
      and because of the sampling procedure, which intercepted women regardless of
      their reasons for visiting the drug shop. Adjusted rates of ineligibility were
      8.6% and 12.7%, respectively, according to nurse and participant assessment. Both
      nurses and women underestimated the prevalence of hypertension in the present
      group. CONCLUSION: Self-screening among women in rural and peri-urban Tanzania
      with regard to contraindications to COC use was comparable to assessment by
      trained nurses.

PMID- 23859706
TI  - Atom transfer radical polymerization preparation and photophysical properties of
      polypyridylruthenium derivatized polystyrenes.
AB  - A ruthenium containing polymer featuring a short carbonyl-amino-methylene linker
      has been prepared by atom transfer radical polymerization (ATRP). The polymer was
      derived from ATRP of the N-hydroxysuccinimide (NHS) derivative of p-vinylbenzoic
      acid, followed by an amide coupling reaction of the NHS-polystyrene with Ru(II)
      complexes derivatized with aminomethyl groups (i.e., [Ru(bpy)2(CH3-bpy
      CH2NH2)](2+) where bpy is 2,2'-bipyridine, and CH3-bpy-CH2NH2 is 4-methyl-4'
      aminomethyl-2,2'-bipyridine). The Ru-functionalized polymer structure was
      confirmed by using nuclear magnetic resonance and infrared spectroscopy, and the
      results suggest that a high loading ratio of polypyridylruthenium chromophores on
      the polystyrene backbone was achieved. The photophysical properties of the
      polymer were characterized in solution and in rigid ethylene glycol glasses. In
      solution, emission quantum yield and lifetime studies reveal that the polymer's
      metal-to-ligand charge transfer (MLCT) excited states are quenched relative to a
      model Ru complex chromophore. In rigid media, the MLCT-ground state band gap and
      lifetime are both increased relative to solution with time-resolved emission
      measurements revealing fast energy transfer hopping within the polymer. Molecular
      dynamics studies of the polymer synthesized here as well as similar model systems
      with various spatial arrangements of the pendant Ru complex chromophores suggest
      that the carbonyl-amino-methylene linker probed in our target polymer provides
      shorter Ru-Ru nearest-neighbor distances leading to an increased Ru*-Ru energy
      hopping rate, compared to those with longer linkers in counterpart polymers. 

PMID- 23859707
TI  - Pre-eclampsia is associated with, and preceded by, hypertriglyceridaemia: a meta
      analysis.
AB  - BACKGROUND: Elevated triglycerides are a feature of the metabolic syndrome,
      maternal obesity, maternal vasculitis (i.e. systemic lupus erythematosus) and
      diabetes mellitus. These conditions are all known risk factors for pre-eclampsia.
      Hypertriglyceridaemia therefore may be associated with pre-eclampsia and indeed
      this may precede the presence of overt disease. OBJECTIVE: In this study we
      determine the association between hypertriglyceridaemia and pre-eclampsia in
      pregnant women. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Web of Science,
      Excerpta Medica Database, ISI Web of Knowledge, Cumulative Index to Nursing and
      Allied Health Literature, Cochrane Library from inception until June 2012 and
      reference lists of relevant studies. SELECTION CRITERIA: Two reviewers
      independently selected studies on pregnant women where triglycerides were
      measured and women were followed up until the development of pre-eclampsia or
      selected on the basis of presence of pre-eclampsia and compared with controls.
      DATA COLLECTION AND ANALYSIS: We collected and meta-analysed the weighted mean
      differences (WMDs) of triglyceride levels from individual studies using a random
      effects model. MAIN RESULTS: We found strong evidence from meta-analysis of 24
      case-control studies (2720 women) that pre-eclampsia is associated with higher
      levels of serum triglycerides (WMD 0.78 mmol/l, 95% confidence interval 0.6-0.96,
      P < 0.00001). This finding is also confirmed in five cohort studies, that
      recruited 3147 women in the second trimester before the onset of pre-eclampsia,
      which proves that hypertriglyceridaemia precedes the onset of pre-eclampsia (WMD
      0.24 mmol/l, 95% confidence interval 0.13-0.34, P < 0.0001). AUTHOR'S
      CONCLUSIONS: Hypertriglyceridaemia is associated with and precedes the onset of
      pre-eclampsia. Further research should focus on defining the prognostic accuracy
      of this test to identify women at risk and the beneficial effect of triglyceride
      lowering therapies in pregnancy.

PMID- 23859709
TI  - Role of dopants in long-range charge carrier transport for p-type and n-type
      graphene transparent conducting thin films.
AB  - Monolayer to few-layer graphene thin films have several attractive properties
      such as high transparency, exceptional electronic transport, mechanical
      durability, and environmental stability, which are required in transparent
      conducting electrodes (TCs). The successful incorporation of graphene TCs into
      demanding applications such as thin film photovoltaics requires a detailed
      understanding of the factors controlling long-range charge transport. In this
      study, we use spectroscopic and electrical transport measurements to provide a
      self-consistent understanding of the macroscopic (centimeter, many-grain scale)
      transport properties of chemically doped p-type and n-type graphene TCs. We
      demonstrate the first large-area n-type graphene TCs through the use of hydrazine
      or polyethyleneimine as dopants. The n-type graphene TCs utilizing PEI, either as
      the sole dopant or as an overcoat, have good stability in air compared to TCs
      only doped with hydrazine. We demonstrate a shift in Fermi energy of well over 1
      V between the n- and p-type graphene TCs and a sheet resistance of ~50 Omega/sq
      at 89% visible transmittance. The carrier density is increased by 2 orders of
      magnitude in heavily doped graphene TCs, while the mobility is reduced by a
      factor of ~7 due to charged impurity scattering. Temperature-dependent
      measurements demonstrate that the molecular dopants also help to suppress
      processes associated with carrier localization that may limit the potential of
      intrinsic graphene TCs. These results suggest that properly doped graphene TCs
      may be well-suited as anodes or cathodes for a variety of opto-electronic
      applications.

PMID- 23859708
TI  - Epigenetic repression of bone morphogenetic protein receptor II expression in
      scleroderma.
AB  - Germline mutations in the bone morphogenetic protein type II receptor (BMPRII)
      gene play an essential role in the pathogenesis of familial pulmonary arterial
      hypertension (FPAH). In view of the histological similarities between scleroderma
      (SSc) and FPAH arterial lesion, we examined the expression levels of BMPRII in
      SSc microvascular endothelial cells (MVEC). Oxidative stress and serum starvation
      were used to examine apoptotic responses of MVECs. BMPRII expression levels were
      determined by RT-PCR and by Western blot. Epigenetic regulation of BMPRII
      expression was examined by the addition of epigenetic inhibitors to MVECs
      cultures, by methylation-specific PCR, and by sequence analysis of DNA
      methylation pattern of the BMPRII promotor region. SSc-MVECs were more sensitive
      to apoptotic signals than were normal-MVECs. A significant decrease in BMPRII
      expression levels in SSc-MVECs was noted, whereas no significant differences in
      the expression levels of BMPRIA and BMPRIB were observed. Similar reduction in
      expression levels was noted in SSc skin biopsies. The expression level of BMPRII
      in SSc-MVECs was normalized by the addition of 2-deoxy-5-azacytidine and
      trichostatin A to cell cultures. Extensive CpG sites methylation in the BMPRII
      promoter region was noted in SSc-MVECs with no detectable site methylation in
      control-MVECs. SSc-MVECs are more sensitive to apoptotic triggers than are
      control-MVECs. The enhanced apoptosis may be related to epigenetic repression of
      BMPRII expression as apoptosis of control-MVECs can be augmented by knocking down
      BMPRII expression. The role of BMPRII underexpression in the pathogenesis of SSc
      vasculopathy is suggested and should be investigated further. 

PMID- 23859710
TI  - Tuning chemical and physical cross-links in silk electrogels for morphological
      analysis and mechanical reinforcement.
AB  - Electrochemically controlled, reversible assembly of biopolymers into hydrogel
      structures is a promising technique for on-demand cell or drug encapsulation and
      release systems. An electrochemically sol-gel transition has been demonstrated in
      regenerated Bombyx mori silk fibroin, offering a controllable way to generate
      biocompatible and reversible adhesives and other biomedical materials. Despite
      the involvement of an electrochemically triggered electrophoretic migration of
      the silk molecules, the mechanism of the reversible electrogelation remains
      unclear. It is, however, known that the freshly prepared silk electrogels (e
      gels) adopt a predominantly random coil conformation, indicating a lack of cross
      linking as well as thermal, mechanical, and morphological stabilities. In the
      present work, the tuning of covalent and physical beta-sheet cross-links in silk
      hydrogels was studied for programming the structural properties. Scanning
      electron microscopy (SEM) revealed delicate morphology, including locally aligned
      fibrillar structures, in silk e-gels, preserved by combining glutaraldehyde-cross
      linking and ethanol dehydration. Fourier transform infrared (FTIR) spectroscopic
      analysis of either electrogelled, vortex-induced or spontaneously formed silk
      hydrogels showed that the secondary structure of silk e-gels was tunable between
      non-beta-sheet-dominated and beta-sheet-dominated states. Dynamic oscillatory
      rheology confirmed the mechanical reinforcement of silk e-gels provided by
      controlled chemical and physical cross-links. The selective incorporation of
      either chemical or physical or both cross-links into the electrochemically
      responsive, originally unstructured silk e-gel should help in the design for
      electrochemically responsive protein polymers.

PMID- 23859711
TI  - Genetic associations with hypertension: meta-analyses of six candidate genetic
      variants.
AB  - AIMS: The aim of this study was to perform combined analyses of six genetic
      variants for the risk of hypertension. METHODS: After a comprehensive literature
      search for genetic variants involved with the association study of hypertension,
      we harvested a total of five genes (six variants) for the current meta-analyses.
      These genes consisted of CYP4A11 (T8590C), RGS2 (1891-1892del TC and G638A),
      HTR2A (T102C), GNAS (T393C), and HSD3B1 (T->C Leu338). RESULTS: A total of 20
      studies among 13,816 cases and 19,248 controls were retrieved for the meta
      analyses of six genetic variants. It was shown that the RGS2 1891-1892del TC
      (OR=1.10, 95% CI=1.02-1.19, p=0.02) polymorphism and the CYP4A11 T8590C (OR=1.19,
      95% CI=1.00-1.41, p=0.05) polymorphism were significantly associated with
      increased risk of hypertension. No association was found between the other four
      variants and the risk of hypertension. CONCLUSION: This meta-analysis revealed
      that the RGS2 1891-1892del TC polymorphism and CYP4A11 T8590C polymorphism were
      associated with hypertension risk. However, HSD3B1 T->C Leu338, HTR2A T102C, GNAS
      T393C, and RGS2 G638A polymorphisms were not associated with hypertension risk.

PMID- 23859712
TI  - Oligodeoxynucleotides containing multiple thiophene-modified isomorphic
      fluorescent nucleosides.
AB  - 5-(Thien-2-yl)-2'-deoxyuridine, an isomorphic fluorescent nucleoside analogue,
      was incorporated into multiple positions within single stranded
      oligodeoxynucleotides. With minimal impact on duplex stability and overall
      structure, oligonucleotides containing three identical isomorphic fluorescent
      nucleosides in alternating or neighboring positions display enhanced, sequence
      dependent on-signals for either duplex formation or dissociation. 

PMID- 23859713
TI  - Perspectives on the reduction in cardiovascular mortality with oral appliance
      therapy for patients with severe obstructive sleep apnoea intolerant to
      continuous positive airway pressure.

PMID- 23859714
TI  - Subcapsular liver hematoma after colonoscopy diagnosed by emergency department
      bedside ultrasonography.
AB  - BACKGROUND: Hepatic subcapsular hematoma is an uncommon cause of right upper
      quadrant pain in the Emergency Department. It must be recognized early, as large
      volumes of acute blood loss and rupture into the peritoneum carry significant
      morbidity and mortality. In the absence of gallbladder disease, the differential
      diagnosis should include liver pathology. Bedside ultrasonography can be used to
      identify such lesions. OBJECTIVES: To discuss the presentation, evaluation, and
      management options of hepatic subcapsular hematoma. CASE REPORT: We report a case
      of a 30-year-old woman who presented with the chief complaint of right upper
      quadrant pain radiating to the right scapula 6 h after a screening colonoscopy
      for intestinal polyps. Emergency physician-performed bedside ultrasound revealed
      a large hyperechoic mass in the right lobe of the liver. Radiology-performed
      comprehensive ultrasound and subsequent computed tomography scan of her abdomen
      and pelvis revealed a subcapsular hematoma without intestinal perforation.
      CONCLUSION: In a patient with undifferentiated right upper quadrant abdominal
      pain, bedside ultrasonography is a rapid and effective modality in the diagnosis
      of liver masses, including subcapsular hematoma.

PMID- 23859715
TI  - Simulation of the cavity-binding site of three bacterial multicopper oxidases
      upon complex stabilization: interactional profile and electron transference
      pathways.
AB  - Previous studies have shown that multicopper oxidases (MCOs) oxidize organic and
      inorganic compounds through oxidation-reduction reactions in which three
      structurally and functionally arranged copper centers coordinate the uptake of an
      electron from a reduced substrate. Structural comparisons among three bacterial
      MCOs, with high structural homology and available three-dimensional information,
      reveal that the primary structural differences between these MCOs are located
      near the mononuclear copper center (T1Cu), where substrate oxidation occurs, as
      opposed to where the reduction of oxygen to water occurs at the trinuclear
      center. Nevertheless, this substrate oxidation is achieved through an outer
      sphere electron transfer mechanism that does not generate a stable substrate
      enzyme complex. In this study, MCOs from Thermus thermophilus (Tth-MCO), Bacillus
      subtilis (CotA), and Escherichia coli (CueO), which have been previously
      determined through X-ray crystallography, were used as models to analyze the
      binding modes of these MCOs to three organic molecules, with specific interest in
      the substrate-binding site. The binding mode of the electron-donor molecule to
      the electron transfer binding site was primarily attributed to hydrophobic
      contacts, which likely play an important role in the determination of substrate
      specificity. Some complexes generated in this study showed an electron donor
      molecule conformation in which an electron could be directly transferred to the
      histidines coordinating T1Cu, while for others additional electron transference
      pathways were also possible through the participation of charged residues during
      electron transfer. 

PMID- 23859716
TI  - Toward understanding the recent large reductions in the proportion of young
      persons with a driver's license: a response to Le Vine et al. (2013).

PMID- 23859717
TI  - Inheritance and Myelodysplasia progression.

PMID- 23859718
TI  - Ineffective breathing pattern: defining characteristics in children with acute
      respiratory infection.
AB  - PURPOSE: To determine the accuracy of NANDA-I defining characteristics for the
      nursing diagnosis, ineffective breathing pattern, in children with acute
      respiratory infection. METHODS: This was a prospective cohort study in 136
      children. Measures of accuracy were calculated for the defining characteristics.
      FINDINGS: Use of accessory muscles to breathe presented the best measure of
      accuracy. Alterations in depth of breathing presented a high value of
      sensitivity. Altered chest excursion and orthopnea presented high values of
      specificity. CONCLUSIONS: Use of accessory muscles to breathe showed the best
      predictive capacity for ineffective breathing pattern. IMPLICATIONS FOR NURSING
      PRACTICE: Measures of accuracy can contribute to an accurate diagnostic inference
      process, improving patient assessment and facilitating rapid, accurate diagnosis.

PMID- 23859719
TI  - Changes in anthropometry and mortality in maintenance hemodialysis patients in
      the HEMO Study.
AB  - BACKGROUND: Poor nutritional status has been associated with worse patient
      survival in maintenance hemodialysis patients. Anthropometric values are
      important nutritional measures, incorporating muscle and fat mass. However, the
      association of changes in anthropometry, including midarm circumference (MAC) and
      skinfold measurements, with mortality in hemodialysis patients remains unknown.
      Accordingly, we explored this association in the Hemodialysis (HEMO) Study. STUDY
      DESIGN: Post hoc analysis of cohort data from a clinical trial. SETTING &
      PARTICIPANTS: 1,846 hemodialysis patients enrolled in the HEMO Study. PREDICTORS:
      MAC and skinfold measurements. OUTCOMES: Longitudinal changes in MAC and
      skinfolds were jointly modeled using repeated measures and survival modeling.
      Time-to-event outcomes were all-cause mortality, cardiac death and
      hospitalization, and infection-related death. RESULTS: Mean MAC was 30.1 cm, and
      mean baseline sum of subscapular, biceps, and triceps skinfolds was 42.4 mm.
      During a median follow-up of 2.5 years, there were 845 deaths. During follow-up,
      MAC and the skinfold measurement declined 0.26 cm and 1.1 mm per year,
      respectively. Declines in MAC (per cm) and skinfold (per mm) measurements were
      associated with higher all-cause mortality (HRs of 1.58 [95% CI, 1.29-1.94; P <
      0.001] and 1.06 [95% CI, 0.99-1.13; P = 0.09], respectively), poorer cardiac
      outcomes (HRs of 1.49 [95% CI, 1.23-1.81; P < 0.001] and 1.05 [95% CI, 0.99-1.10;
      P = 0.09], respectively), and higher infection-related hospitalization (HRs of
      2.45 [95% CI, 1.55-3.88; P < 0.001] and 1.16 [95% CI, 0.98-1.37; P = 0.08],
      respectively). The association between declining MAC and skinfold with patient
      survival was most notable for those with body mass index (BMI) <=25 kg/m2 (HRs of
      2.41 [95% CI, 1.81-3.19; P < 0.001] and 1.22 [95% CI, 1.10-1.35; P < 0.001],
      respectively). LIMITATIONS: Prevalent dialysis patients only, excluding
      individuals weighing >85 kg. CONCLUSIONS: Declines in skinfold thickness were not
      associated significantly with outcomes except for participants with BMI <=25
      kg/m2. Declines in MAC are associated significantly with all-cause mortality and
      cardiac outcomes in hemodialysis patients, most notably in those with BMI <=25
      kg/m2.

PMID- 23859721
TI  - Interdevice baseline signal magnitude variability of the ActivPAL3 activity
      monitor.
AB  - The aim of this study was to evaluate the interdevice variability in baseline
      signal magnitude of the ActivPAL3 (PALTechnologies, Glasgow, UK) activity
      monitor. Twenty consecutively numbered ActivPAL3 triaxial physical activity
      monitors were assessed for baseline signal magnitudes oriented in the X (vertical
      standing), Y (side lying), and Z (lying flat) planes. Data was recorded for 60s
      in each orientation and the three orthogonal axes were analysed for baseline
      signal magnitude each orientation. Our batch of devices demonstrated
      approximately 6.6% difference in raw acceleration calibration values compared to
      manufacturer specifications. Analysis of interdevice variability revealed three
      devices which exhibited baseline signal variability greater than 1.96 SD of the
      group mean. The impact of interdevice variability in baseline signal magnitude on
      data collection is unknown, however, supports the argument in the literature for
      the systematic checking of interdevice variability as routine maintenance.

PMID- 23859720
TI  - Using glycosaminoglycan/chemokine interactions for the long-term delivery of 5P12
      RANTES in HIV prevention.
AB  - 5P12-RANTES is a recently developed chemokine analogue that has shown high level
      protection from SHIV infection in macaques. However, the feasibility of using
      5P12-RANTES as a long-term HIV prevention agent has not been explored partially
      due to the lack of available delivery devices that can easily be modified for
      long-term release profiles. Glycosaminoglycans (GAGs) have been known for their
      affinity for various cytokines and chemokines, including native RANTES, or CCL5.
      In this work, we investigated used of GAGs in generating a chemokine drug
      delivery device. Initial studies used surface plasmon resonance analysis to
      characterize and compare the affinities of different GAGs to 5P12-RANTES. These
      different GAGs were then incorporated into drug delivery polymeric hydrogels to
      engineer sustained release of the chemokines. In vitro release studies of 5P12
      RANTES from the resulting polymers were performed, and we found that 5P12-RANTES
      release from these polymers can be controlled by the amount and type of GAG
      incorporated. Polymer disks containing GAGs with stronger affinity to 5P12-RANTES
      resulted in more sustained and longer term release than did polymer disks
      containing GAGs with weaker 5P12-RANTES affinity. Similar trends were observed by
      varying the amount of GAGs incorporated into the delivery system. 5P12-RANTES
      released from these polymers demonstrated good levels of CCR5 blocking, retaining
      activity even after 30 days of incubation. 

PMID- 23859722
TI  - Survey of South African fruit juices using a fast screening HILIC-MS method.
AB  - Adulteration of fruit juices--by the addition of sugar or other less expensive
      fruit juices as well as preservatives, artificial sweeteners and colours--was
      tested for by using a developed screening method. The method employs hydrophilic
      interaction liquid chromatography-mass spectrometry (HILIC-MS) using electrospray
      ionisation in the negative mode and ultraviolet light detection. Different fruit
      juices can be differentiated by the content of marker compounds like sorbitol,
      certain phenolic molecules and their saccharide profile. This method was used to
      test 46 fruit juice samples from the retail market as well as 12 control samples.
      The study focused on the main types of fruit juices consumed on the South African
      market including apple, orange, grape and blends of these juices with other
      fruits like mango, pear and guava. Overall, the 46 samples tested mostly agreed
      with label claims. One grape juice sample was adulterated, probably with apple
      juice. Natamycin above the legal limits was found in two samples. In addition,
      two samples contained natamycin and one sample benzoate without it being
      indicated on the label. The method is well suited as a quick screening method for
      fruit juice adulteration and if used routinely would reduce fruit juice
      adulteration without the cost of the current array of tests needed for
      authenticity testing.

PMID- 23859723
TI  - Institutional isolation and crime: The mediating effect of disengaged youth on
      levels of crime.
AB  - We propose that structural resource deprivation and a weak civic participatory
      culture foster institutional isolation among youth, which, in turn, elevates
      rates of crime. Robust institutional attachments are essential to mainstream
      cultural learning, the internalization of mainstream values, the development of
      local network ties, and pro-social behavior. Communities that fail to embed
      residents, particularly youth, within a conventional institutional framework are
      ill-equipped for concerted action and unable to defend community interest and
      solve common problems, including crime. Using county-level census data we
      identify a group of youth who are simultaneously disengaged from a wide swath of
      mainstream social institutions, those we term "floaters." Analyses of aggregate
      levels of homicide, aggravated assault, robbery, and burglary around 2000 offer
      strong support for a mediation model indicating that structural deprivation and a
      weak civic participatory culture increase the presence of floaters which, in
      turn, raises levels of violent and property crime. We discuss the implications of
      our findings. 

PMID- 23859724
TI  - Does it matter if teachers and schools match the student? Racial and ethnic
      disparities in problem behaviors.
AB  - Black youth often lag behind their non-Hispanic white peers in educational
      outcomes, including teacher-evaluated school performance. Using data from four
      waves of the Early Childhood Longitudinal Study-Kindergarten Cohort, the analyses
      presented here identify the extent to which children receive different
      evaluations from their teachers depending on the racial/ethnic match of teachers
      and students. This study is distinct from previous work because we examine the
      assessment of an individual child by multiple teachers. The results indicate that
      Black children receive worse assessments of their externalizing behaviors (e.g.
      arguing in class and disrupting instruction) when they have a non-Hispanic white
      teacher than when they have a Black teacher. Further, these results exist net of
      school context and the teacher's own ratings of the behavior of the class
      overall. 

PMID- 23859725
TI  - A double standard for "Hooking Up": How far have we come toward gender equality?
AB  - While sexual attitudes have liberalized in the past half century, research is
      mixed as to whether attitudes have become less gendered over time. Recent studies
      on college students' sexual and romantic relationships suggest that a sexual
      double standard continues to organize sexuality on many campuses. Data from the
      Online College Social Life Survey shed light on students' evaluation of casual
      sex, or "hooking up." In addition to exploring gendered attitudinal patterns, we
      use gender structure theory to explore how individual characteristics and
      normative expectations of campus group affiliations shape attitudes. While three
      quarters of students do not hold different standards for men and women's hooking
      up, attitudes are more conservative than liberal, with almost half of students
      losing respect for men and women who hook up "a lot." However, men are more
      likely to hold a traditional double standard, while women are more likely to
      espouse egalitarian conservative attitudes. Individual characteristics, including
      age, religion, race, social class and sexual orientation are frequently related
      to sexual attitudes, as are number of hook ups, fraternity/sorority affiliation
      and varsity athletic participation. 

PMID- 23859726
TI  - Structural bias in the sentencing of felony defendants.
AB  - As incarceration rates have risen in the US, so has the overrepresentation of
      African Americans and Latinos among prison inmates. Whether and to what degree
      these disparities are due to bias in the criminal courts remains a contentious
      issue. This article pursues two lines of argument toward a structural account of
      bias in the criminal law, focusing on (1) cumulative disadvantages that may
      accrue over successive stages of the criminal justice process, and (2) the
      contexts of racial disadvantage in which courts are embedded. These arguments are
      tested using case-level data on male defendants charged with felony crimes in
      urban US counties in 2000. Multilevel binary and ordinal logit models are used to
      estimate contextual effects on pretrial detention, guilty pleas, and sentence
      severity, and cumulative effects are estimated as conditional probabilities that
      are allowed to vary by race across all three outcomes. Results yield strong, but
      qualified, evidence of cumulative disadvantage accruing to black and Latino
      defendants, but do not support the contextual hypotheses. When the cumulative
      effects of bias are taken into account, the estimated probability of the average
      African American or Latino felon going to prison is 26% higher than that of the
      average Anglo. 

PMID- 23859727
TI  - There's no place like home: Examining the emotional consequences of Hurricane
      Katrina on the displaced residents of New Orleans.
AB  - Using survey data from the Displaced New Orleans Residents Pilot Study (DNORPS),
      I examine the emotional consequences of Hurricane Katrina on the displaced
      residents of New Orleans. First, I employ an established framework within
      disaster research to investigate whether the stress level of displaced residents
      varies by race, income, and gender. As the residents in this dataset remained
      uprooted from their homes, I also examine three housing variables, including
      homeownership status, house type, and four levels of home damage. Contrary to
      previous research, home damage and homeownership status are significant
      predictors of displaced residents' emotional distress while the effect of race
      disappears. These findings suggest that future research on the mental health of
      disaster survivors, especially for displaced residents, expand the traditional
      analytical framework to consistently include housing variables, especially
      different categories of home damage, in addition to race, income, and gender. 

PMID- 23859728
TI  - Categorical sources of varieties of network inequalities.
AB  - Dominant gender and ethnic groups do have more social capital than their less
      dominant counterparts, but there are variations in the types of social capital to
      which they have access. This study of Singapore finds that men have greater
      access than women to forms of social capital such as ties to men, weak ties, and
      non-kin. By contrast, Chinese Singaporeans have greater access to forms of social
      capital such as ties to university graduates, private housing dwellers, Chinese,
      and weak ties, than do other ethnicities. These distinctive patterns of network
      inequalities are bound up with distinctive patterns of access to organizations
      such as schools, workplaces, and voluntary associations. The paper finds that
      network inequalities among gender and ethnic groups have more to do with barriers
      of entry to those organizations and less to do with social capital being added
      more efficaciously for some members. The paper underscores a need to better
      understand the complex intersections between ascriptive social categories,
      organizations, and social capital. 

PMID- 23859729
TI  - Dropping out of high school: Effects of close and distant friendships.
AB  - Prior research highlights the role of friends in influencing whether a student
      completes high school. Students who drop out tend to have fewer friends, as well
      as friends who are less oriented toward school success. We distinguish between
      close and distant friendships by developing a theoretical framework which
      predicts close and distant friends likely have distinct effects on dropping out.
      Close friendships provide valuable emotional support, and forging numerous close
      friendships at school should decrease one's risk of dropping out. In contrast,
      the characteristics of distant friends help shape students' social identities and
      beliefs about "what's normative." Our analyses of the Add Health data set confirm
      our expectations. Students with more close friendships are less likely to drop
      out, but close friends' characteristics are unrelated to dropping out. Distant
      relationships (as measured by affect and regularity of interaction) with friends
      who have a high risk of dropping out significantly increase a student's own risk
      of dropping out. 

PMID- 23859730
TI  - How do sexual harassment policies shape gender beliefs? An exploration of the
      moderating effects of norm adherence and gender.
AB  - Sexual harassment laws have led to important organizational changes in the
      workplace yet research continues to document resistance to their implementation
      and backlash against the people who mobilize such laws. Employing experimental
      research methods, this study proposes and tests a theory specifying the
      mechanisms through which sexual harassment policies affect gender beliefs. The
      findings show evidence that sexual harassment policies strengthen unequal gender
      beliefs among men and women most committed to traditional gender interaction
      norms. I also find that men and women's different structural locations in the
      status hierarchy lead to different, but related sets of concerns about the status
      threats posed by sexual harassment policies. By specifying the social
      psychological processes through which sexual harassment law affects beliefs about
      men and women, this study sets the stage for investigating ways to make laws
      designed to reduce inequality between social groups more effective. 

PMID- 23859731
TI  - Pathways of children's long-term living arrangements: A latent class analysis.
AB  - This study employed latent class analysis to create children's family structure
      trajectories from birth through adolescence using merged mother and child data
      from the National Longitudinal Survey of Youth (N=1870). Input variables
      distinguished between biological fathers and stepfathers as well as mother's
      marriages and cohabitations. The best-fitting model revealed five latent
      trajectories of children's long-term family structure: continuously married
      biological parents (55%), long-term single mothers (18%), married biological
      parents who divorce (12%), a highly unstable trajectory distinguished by gaining
      at least one stepfather (11%), and cohabiting biological parents who either marry
      or break up (4%). Multinomial logistic regression indicated that mother's
      education, race, teen birth status, and family of origin characteristics were
      important predictors of the long-term family trajectories in which their children
      grew up. These findings suggest that latent class analysis is a valuable
      statistical tool for understanding children's complete family structure
      experiences. 

PMID- 23859733
TI  - Domestic outsourcing and multitasking: How much do they really contribute?
AB  - The bulk of responsibility for domestic work and childcare in heterosexual
      couples falls on women. But the means they find to cope with this load, and how
      these means relate to the factors underpinning the division of labor are not
      often studied. Two much-cited ways of reducing overall work time are purchasing
      domestic assistance (outsourcing) and the multitasking of domestic/caring tasks.
      Using UK 2000/2001 time-use data (N=4196 couples), we find domestic outsourcing
      is related to having dependent children and to partners' resources, but has
      little impact on the total domestic/caring workload of either partner. Nor can
      outsourcing account for the reduction in women's unpaid labor with increasing
      economic resources. Wives spend more time multitasking than husbands, but their
      proportion of multitasked domestic time is similar, and is not affected by
      resources or dependent children. Domestic multitasking seems to be more related
      to opportunity (time at home) than to time pressure. 

PMID- 23859732
TI  - The differential contributions of teen drinking homophily to new and existing
      friendships: An empirical assessment of assortative and proximity selection
      mechanisms.
AB  - Alcohol use is pervasive in adolescence. Though most research is concerned with
      how friends influence drinking, alcohol is also important for connecting teens to
      one another. Prior studies have not distinguished between new friendship
      creation, and existing friendship durability, however. We argue that accounting
      for distinctions in creation-durability processes is critical for understanding
      the selection mechanisms drawing drinkers into homophilous friendships, and the
      social integration that results. In order to address these issues, we
      appliedstochastic actor based models of network dynamics to National Longitudinal
      Study of Adolescent Health data. Adolescents only modestly prefer new friendships
      with others who drinker similarly, but greatly prefer friends who indirectly
      connect them to homophilous drinkers. These indirect homophilous drinker
      relationships are shorter lived, however, and suggest that drinking is a social
      focus that connects adolescents via proximity, rather than assortativity. These
      findings suggest that drinking leads to more situational and superficial social
      integration. 

PMID- 23859734
TI  - Gender and migration on the labour market: Additive or interacting disadvantages
      in Germany?
AB  - Despite substantial differences in labour market attainment according to gender
      and migration status, gender and ethnic differences in labour market behaviour
      are most often studied separately. In contrast, this study describes and analyses
      interactions between gender, ethnic background and immigrant generation with
      regard to labour market participation, part-time work, and occupational status.
      The double comparison aims to reveal whether gender gaps in these labour market
      outcomes among the majority population generalise to ethnic minorities. Moreover,
      we ask whether variation in gender gaps in labour market behaviour follows the
      patterns in migrants' origin countries, and whether gender gaps show signs of
      intergenerational assimilation. Our heterogeneous choice and OLS regressions of
      2009 German Microcensus data reveal considerable variation in gender gaps in
      labour market behaviour between East and West Germany, across ethnic groups and
      across generations. Intergenerational comparisons show that most ethnic
      minorities assimilate towards German patterns of gendered labour market
      attainment. 

PMID- 23859735
TI  - Predicting social influence with faction sizes and relative status.
AB  - Building on a recent theoretical development in the field of sociological social
      psychology, we develop a formal mathematical model of social influence processes.
      The extant theoretical literature implies that factions and status should have
      non-linear effects on social influence, and yet these theories have been
      evaluated using standard linear statistical models. Our formal model of influence
      includes these non-linearities, as specified by the theories. We evaluate the fit
      of the formal model using experimental data. Our results indicate that a one
      parameter mathematical model fits the experimental data. We conclude with the
      implications of our research and a discussion of how it may be used as an impetus
      for further work on social influence processes. 

PMID- 23859736
TI  - New evidence on racial and ethnic disparities in homeownership in the United
      States from 2001 to 2010.
AB  - Using 2001-2010 homeownership data for the United States we analyze changes in
      racial and ethnic disparities between whites and blacks, Asians, Mexicans,
      Cubans, Puerto Ricans and other Hispanics. We employ Integrated Public Use
      Microdata (IPUMS) combined with local credit scores and house price to income
      ratios. Controlling for demographic, income, wealth, employment, and housing
      characteristics, we find no significant differences between whites and Asians,
      Mexicans, or Cubans. Conversely, blacks and Puerto Ricans remain substantially
      disadvantaged. We conduct further analysis for the 2001-2003, 2004-2007, and 2008
      2010 periods of the housing boom and collapse. Blacks and Puerto Ricans
      experienced decreased disparities during the peak years of the boom. Puerto Rican
      parity with whites continued to improve during the crash while gains among blacks
      eroded. The results suggest the homeownership differences between whites, Asians,
      Mexicans, and Cubans are apparently explained by socioeconomic status while
      racial disparities among blacks and Puerto Ricans evolved but continue to
      persist. 

PMID- 23859737
TI  - Immigrant and native financial well-being: The roles of place of education and
      race/ethnicity.
AB  - Immigrants' integration into U.S. society has occupied the interest of both
      scholars and the general public throughout the nation's history. This paper draws
      on and refines dominance-differentiation theory to explore how immigrants' place
      of education (whether they completed their education in the United States or
      abroad) and racial/ethnic status differentially affect their ability to integrate
      into U.S. society. Using the Survey of Income and Program Participation and
      wealth attainment as an indicator of economic integration, this paper finds mixed
      evidence for dominance-differentiation theory. Foreign education is associated
      with lower wealth attainment and race/ethnicity serves as an important
      stratifying factor for blacks and Latinos; however, there is little support for
      the theory when comparing the wealth attainment of immigrants with their same
      race/co-ethnic native-born peers. This paper concludes with a discussion of why
      place of education matters for wealth attainment in the United States and
      explores its implications for both educational and racial/ethnic stratification
      among U.S. immigrants. 

PMID- 23859738
TI  - Exploring the spatial wage penalty for women: Does it matter where you live?
AB  - Inequality between men and women has decreased over the past four decades in the
      US, but wage inequality among groups of women has increased. As metropolitan
      women's earnings grew by 25% over the past four decades, nonmetropolitan women's
      earnings only grew by 15%. In the current study we draw on data from the Current
      Population Survey to analyze the spatial wage gap among women. We explore
      differences in the spatial wage gap by education, occupation, and industry.
      Regression models that control for marriage, motherhood, race, education, region,
      age, and work hours indicate that metropolitan women earn 17% more per hour than
      nonmetropolitan women. Nonmetropolitan women earn less than metropolitan women
      who live in central cities and outside central cities. The gap in metropolitan
      nonmetropolitan wages is higher for more educated women than for less educated
      women. The wage gap is only 5% for women without a high school degree, but it is
      15% for women with a college degree and 26% for women with an advanced degree.
      Nonmetropolitan college graduates are overrepresented in lower-paying occupations
      and industries. Metropolitan college graduates, however, are overrepresented in
      higher-paying occupations and industries, such as professional services and
      finance. 

PMID- 23859739
TI  - New strategies for biosample collection in population-based social research.
AB  - This paper aims to increase understanding of the methodological issues involved
      in adding biomeasures to social research by investigating the potential of an
      event-triggered, self-collection technique for monitoring biological response to
      social events. We use data from the Relationship Dynamics and Social Life (RDSL)
      study, which collected saliva samples triggered by a life event important to the
      aims of the study - the end of a romantic relationship. Our investigation found
      little evidence that those who complied in the biosample collection were
      different from those who did not comply in terms of key study measures and
      sociodemographic characteristics. We also found no evidence that the biosample
      collection had adverse consequences for subsequent panel participation. We did
      find that prior cooperation in the study was an important predictor of biosample
      cooperation, which is important information in developing biosample collection
      strategies. As demand for biological samples directly linked to social data
      continues to grow, effective low-cost collection methods will become increasingly
      valuable. The evidence here indicates that self-collected biosamples may offer
      tremendous potential to meet this demand. 

PMID- 23859740
TI  - Effect of applied moment on resistance to sliding among esthetic self-ligating
      brackets.
AB  - OBJECTIVE: To determine the effect of mode of ligation and bracket material on
      resistance to sliding (RS) by comparing various esthetic brackets of
      conventionally ligated and self-ligating (SL) designs under an increasing applied
      moment in the second-order dimension. MATERIALS AND METHODS: Eight different
      commercially available esthetic brackets of SL and conventional elastomeric
      ligated (CL) designs were mounted on a testing apparatus to simulate canine
      retraction using sliding mechanics and the application of a moment on
      0.019"*0.025" stainless steel archwire. The samples examined were the CL brackets
      ClarityTM, Inspire IceTM, SpiritMBTM, and MystiqueTM, and the SL brackets
      ClaritySLTM, In-OvationCTM, In-OvationRTM, and SmartclipTM. The RS at calculated
      moments of 2000 g-mm and 4000 g-mm was determined and compared between the
      various brackets. Descriptive measures and one-way analysis of variance were used
      to calculate means and statistical differences among the bracket types. RESULTS:
      The CL monocrystalline bracket displayed significantly greater (P < .05) RS than
      all other brackets tested. Among the other brackets, the range of RS values was
      145.8-191.7 g and 291.9-389.2 g at moments of 2000 g-mm and 4000 g-mm,
      respectfully, though these differences were not significant (P < .05). All
      brackets tested displayed greater levels of RS (P < .05) at 4000 g-mm than at
      2000 g-mm. CONCLUSION: With the exception of the CL monocrystalline bracket, all
      brackets displayed comparable amounts of RS regardless of mode of ligation or
      bracket slot material.

PMID- 23859741
TI  - Laparoscopic antireflux surgery in infants with single ventricle physiology: a
      review.
AB  - Laparoscopic fundoplication and gastrostomy tube placement have grown in
      popularity within the pediatric population for treatment of gastroesophageal
      reflux disease and failure to thrive, respectively. One population that has an
      increased need for gastric surgery in infancy is patients with congenital heart
      defects, especially those with "single ventricle physiology." The most common
      defect included in this population is hypoplastic left heart syndrome (HLHS).
      Because of the abnormal physiology present in this condition, there are concerns
      with regard to the use of laparoscopic procedures for gastric surgery in patients
      treated with a three-staged reconstruction. We review the staged reconstruction
      of infants with HLHS, address safety concerns of interstage noncardiac procedures
      on this patient population, and review the current literature regarding outcomes
      of laparoscopic gastric surgery on patients with single ventricle physiology.

PMID- 23859742
TI  - Complete thoracoscopic versus video-assisted thoracoscopic resection of
      congenital lung lesions.
AB  - BACKGROUND: Minimally invasive surgery is recognized as a safe and feasible
      technique for resecting congenital lung lesions. In our hospital, video-assisted
      thoracoscopic surgery (VATS) was initially performed through a 5-6-cm incision
      with several trocars under differential lung ventilation (assisted-VATS).
      Complete thoracoscopic surgery (complete-VATS) with artificial pneumothorax was
      introduced in 2009 and allowed surgery in smaller infants. The aim of this study
      was to compare the outcomes of complete-VATS and assisted-VATS for congenital
      lung lesions. PATIENTS AND METHODS: Between January 2004 and October 2012, 22
      children underwent pulmonary lobectomy by complete-VATS or assisted-VATS at our
      hospital. We retrospectively reviewed the intraoperative and early postoperative
      results of these patients. RESULTS: Of the 22 children, 10 underwent assisted
      VATS, and 12 underwent complete-VATS to treat various diseases, including
      congenital cystic adenomatous malformation, sequestration, and bronchial atresia.
      The age, body weight, and mean operative time were not significantly different
      between the two groups. Four patients in the complete-VATS group, but none in the
      assisted-VATS group, weighed <10 kg. Intraoperative bleeding was significantly
      less, and hospital stay was significantly shorter, in the complete-VATS group.
      One patient in the assisted-VATS group had intraoperative bleeding and required
      conversion to open surgery. Postoperative complications included transient
      paralysis of the affected arm and transient atelectasis in 1 patient each in the
      complete-VATS group. CONCLUSIONS: Complete-VATS can be safely performed with less
      bleeding and shorter hospital stay than assisted-VATS. As differential lung
      ventilation is not essential during complete-VATS, complete-VATS can be performed
      in small infants.

PMID- 23859743
TI  - Safety and efficacy of barbed suture for gastrointestinal suture: a prospective
      and randomized study on obese patients undergoing gastric bypass.
AB  - BACKGROUND: Laparoscopic intracorporeal suturing and knot tying for anastomosis
      are considered the most difficult laparoscopic skills to master. The aim of this
      study was to establish the safety and efficacy of barbed suture for intestinal
      sutures to close the gastrojejunal anastomosis in obese patients undergoing
      gastric bypass. STUDY DESIGN: All consecutive patients undergoing gastric bypass
      were screened for enrollment in our study. Patients were randomly allocated to
      undergo knotless anastomosis with barbed suture (V-LocTM 180; Covidien,
      Mansfield, MA) (case group) or knot-tying anastomosis with 3/0 polyglactin
      sutures (Polysorb((r)); Covidien) (control group). The primary outcome was the
      time needed for the gastrojejunal anastomosis and the operative time. The
      secondary outcomes were the incidence of leak, bleeding, and stenosis and the
      evaluation of the cost of the different procedures evaluated. RESULTS: Among the
      60 consecutive patients enrolled in our study, 30 underwent knot-tying
      anastomosis, and 30 underwent knotless anastomosis. The time needed for the
      anastomosis was significantly less (P<.001) in the knotless group, whereas no
      significant differences were found between the two groups for operative time
      (P=.151). We recorded one leak in the control group and one leak in the case
      group (P=1.000). One bleeding in the case group (P=1.000) and no stenosis in
      either group was recorded. Finally, in our experience, the knotless anastomosis
      was cheaper than the knot-tying anastomosis (P<.001). CONCLUSIONS: Our study
      appears to be encouraging to suggest the use of barbed suture for
      gastrointestinal anastomosis.

PMID- 23859744
TI  - Surgical re-interventions following colorectal surgery: open versus laparoscopic
      management of anastomotic leakage.
AB  - BACKGROUND: Increasing numbers of colorectal resections are performed
      laparoscopically each year. In 2010, 42% of all colorectal procedures in The
      Netherlands were performed laparoscopically. Although the anastomotic leakage
      rate is 3%-19% of all patients, little is known about laparoscopic options for re
      intervention. Our study aims to evaluate the safety and feasibility of
      laparoscopic re-intervention compared with open surgery following colorectal
      surgery. PATIENTS AND METHODS: All patients who required a surgical re
      intervention for an anastomotic leak, bowel perforation, or abscess after
      laparoscopic colorectal surgery between January 2008 and June 2012 were analyzed
      retrospectively. Demographic data, operative management, morbidity, hospital
      stay, and mortality were collected and analyzed for each patient. RESULTS: Fifty
      six patients were included. Eighteen patients had a laparotomy following
      laparoscopy, and 38 patients had a laparoscopic re-intervention following
      laparoscopy. The median age was 65 years, with a median body mass index of 26
      kg/m(2). Four patients had a previous laparotomy, and 73% had surgery for
      malignant colorectal disease. The length of hospital stay was 20 days in the
      laparoscopic group versus 31 days in the open group (P=.044). Six out of 38
      versus 7 out of 18 patients required an additional re-intervention (P=.056).
      Fewer patients developed fascial dehiscence in the laparoscopic group (P=.033).
      In-hospital mortality was 4 out of 18 in the open group compared with 2 out of 38
      in the laparoscopic group (P=.077). CONCLUSIONS: Laparoscopic re-intervention
      could be a safe and feasible treatment for anastomotic leakage after laparoscopic
      colorectal surgery. These promising results need to be further investigated in a
      prospective study to reduce uncertainty in the patient's condition and
      perioperative findings.

PMID- 23859745
TI  - Feasibility of transumbilical lung wedge resection in a canine model.
AB  - BACKGROUND: Chronic wound discomfort and intercostal neuralgia are well-known
      postoperative complications of video-assisted thoracoscopic surgery (VATS). To
      explore the possibility of a surgical platform that would cause less
      postoperative discomfort and avoid these complications, this study evaluated the
      feasibility of transumbilical lung wedge resection in a canine model. MATERIALS
      AND METHODS: Twelve dogs (4 in the nonsurvival group and 8 in the survival group)
      were used in this study. Transumbilical thoracoscopy was performed using a
      homemade metallic tube via umbilical and diaphragmatic incisions with the animal
      in a supine position. After thoracic exploration, wedge resection was performed
      on the lung using an endoscopic stapling device placed through the transumbilical
      and transdiaphragmatic incisions under direct bronchoscopic guidance. The animals
      were sacrificed 30 minutes after the procedure (nonsurvival group) or 14 days
      postsurgery (survival group) for necropsy and histological evaluations. RESULTS:
      Eleven preplanned lung wedge resections were completed in a median time of 101
      minutes (range, 65-175 minutes) with one exception due to inadequate stapling in
      the early phase of the experiment. There was one death directly related to
      postoperative massive airleaks and sepsis in the survival group. The other 7
      animals had an uneventful postoperative period. Necropsies at 2 weeks after
      surgery confirmed successful lung resections and revealed no evidence of vital
      organ injury. Two animals exhibited complete healing of the diaphragmatic
      incision. Liver herniation was identified in 1 of 5 animals with partial wound
      healing. CONCLUSIONS: This preliminary animal study demonstrates that large lung
      wedge resection can be performed with mechanical staplers via a single
      transumbilical incision. Future studies will investigate the cardiopulmonary and
      immunologic effects of transumbilical VATS compared with conventional VATS.

PMID- 23859746
TI  - Laparoscopy-assisted vaginal cornual resection for the treatment of large
      interstitial pregnancy.
AB  - PURPOSE: To present the experience of laparoscopy-assisted vaginal cornual
      resection for the treatment of two cases of large interstitial pregnancy.
      SUBJECTS AND METHODS: Surgeons performed laparoscopic cornual resection initially
      for the first case but encountered torrential hemorrhage, which was controlled
      immediately by conversion to the vaginal approach. Following this experience,
      laparoscopy-assisted vaginal cornual resection was performed directly after
      laparoscopic inspection for the second case. RESULTS: Both cases were treated
      successfully by laparoscopy-assisted vaginal cornual resection. Hemostasis and
      uterine repair seem to be easier by the laparoscopy-assisted vaginal route than
      by the purely laparoscopic approach. No similar case has been reported in the
      literature. CONCLUSIONS: Our experience suggests that laparoscopy-assisted
      vaginal cornual resection may be a preferable alternative to laparoscopy in
      treating a large interstitial pregnancy. More studies are needed to confirm this
      finding.

PMID- 23859747
TI  - Urine concentrations of xanthine, hypoxanthine and uric acid in UK Cavalier King
      Charles spaniels.
AB  - OBJECTIVES: Xanthine urolithiasis and asymptomatic xanthinuria have been
      diagnosed in Cavalier King Charles spaniel dogs suggesting that primary
      xanthinuria may be a breed-related disorder, although its prevalence remains
      unclear. The hypothesis of this study was that asymptomatic xanthinuria is common
      in Cavalier King Charles spaniel dogs. METHODS: Free catch urine samples were
      collected from 35 client-owned Cavalier King Charles spaniel dogs and from 24
      dogs of other breeds. The purine metabolites were measured by high-performance
      liquid chromatography. The urine ratios of xanthine/creatinine and
      hypoxanthine/creatinine were calculated and compared between the two groups of
      dogs. RESULTS: The urine concentrations of purine metabolites were not
      significantly different between the two groups and were very low in both. The
      urine concentrations of xanthine in all 35 Cavalier King Charles spaniel were
      markedly lower than in the previously reported case of xanthine urolithiasis in a
      UK Cavalier King Charles spaniel dog. CLINICAL SIGNIFICANCE: Asymptomatic
      xanthinuria was not detected in this UK Cavalier King Charles spaniel population.
      This data may be used as a reference for urinary purine metabolite concentrations
      in the dog.

PMID- 23859748
TI  - Obstructive sleep apnea and autoimmune rheumatic disease: is there any link?
AB  - The association between autoimmune rheumatic diseases and obstructive sleep apnea
      (OSA) is complex. Systemic inflammation secondary to OSA may underlie this
      association. It is possible that OSA-related inflammation may trigger the
      occurrence of autoimmune rheumatic disease in genetically susceptible
      individuals. On the other hand, autoimmune rheumatic diseases can lead to OSA or
      worsen preexisting OSA. Temporomandibular joint destruction, cervical spine
      subluxation and brainstem compression are the factors responsible for the above
      observation. Future studies are needed to clarify whether OSA is an independent
      risk factor for the development of autoimmune disease and whether OSA management
      will lead to a reduction in the incidence of autoimmune disease. On the other
      hand, it is important to treat autoimmune rheumatic disease promptly, to reduce
      the risk of complications, with OSA being one of these. 

PMID- 23859749
TI  - Effect of Nd:YAG laser bleaching and antioxidizing agents on the shear bond
      strength of brackets.
AB  - OBJECTIVE: The aims of this study were to evaluate the effect of hydrogen
      peroxide bleaching agents, both nonactivated and activated by a neodymium:yttrium
      aluminum-garnet (Nd:YAG) laser, and of antioxidant treatment on the shear bond
      strength (SBS) of orthodontic brackets. BACKGROUND DATA: Nd:YAG laser activation
      is expected to accelerate the bleaching therapy without decrease shear bond
      strength. MATERIALS AND METHODS: Ninety extracted maxillary central incisors were
      divided into two experimental groups and a control group. Group I was the control
      group, Group II was bleached with 35% hydrogen peroxide and had no
      photoactivation, and Group III was bleached with 35% hydrogen peroxide with
      activation by a Nd:YAG laser (4.0 W, 60 Hz frequency, 1 mm distance, 20 sec).
      Each group was divided into two subgroups: Subgroup A was immersed in artificial
      saliva for 2 weeks, and then bonded using the total etch system, whereas subgroup
      B was treated with an antioxidant agent (10% sodium ascorbate) and then bonded
      using the same system. The samples were stored in water for 24 h at 37 degrees C,
      and thermocycled. The SBS in megapascals (MPa) was determined by a shear test
      with 1 mm/min crosshead speed, and failure types were classified with modified
      adhesive remnant index scores. The data were analyzed with two way analyses of
      variance, Tukey, and chi(2) tests at the alpha = 0.05 level. RESULTS: In both
      Groups II and III, the SBSs of brackets bonded after bleaching (Group II 15.16,
      Group III 17.50 MPa) were significantly lower than those of brackets in the
      bonded unbleached group (Group I 22.13 MPa); however, sodium ascorbate treatment
      significantly increased the SBSs of brackets in the bleached groups (Group II
      21.52, Group III 22.43 MPa), but had an insignificant effect on the SBS of the
      control group (Group I 23.66MPa). CONCLUSIONS: Hydrogen peroxide bleaching agents
      reduce the SBSs both with and without Nd:YAG laser activation; however, treatment
      of the bleached enamel surface with 10% sodium ascorbate prior to bonding negates
      the effect.

PMID- 23859750
TI  - Photodynamic therapy: occupational hazards and preventative recommendations for
      clinical administration by healthcare providers.
AB  - OBJECTIVE: Photodynamic therapy (PDT) as a medical treatment for cancers is an
      increasing practice in clinical settings, as new photosensitizing chemicals and
      light source technologies are developed and applied. PDT involves dosing patients
      with photosensitizing drugs, and then exposing them to light using a directed
      energy device in order to manifest a therapeutic effect. Healthcare professionals
      providing PDT should be aware of potential occupational health and safety hazards
      posed by these treatment devices and photosensitizing agents administered to
      patients. MATERIALS AND METHODS: Here we outline and identify pertinent health
      and safety considerations to be taken by healthcare staff during PDT procedures.
      RESULTS: Physical hazards (for example, non-ionizing radiation generated by the
      light-emitting device, with potential for skin and eye exposure) and chemical
      hazards (including the photosensitizing agents administered to patients that have
      the potential for exposure via skin, subcutaneous, ingestion, or inhalation
      routes) must be considered for safe use of PDT by the healthcare professional.
      CONCLUSIONS: Engineering, administrative, and personal protective equipment
      controls are recommendations for the safe use and handling of PDT agents and
      light-emitting technologies.

PMID- 23859751
TI  - Morphological analysis of the resin-dentin interface in cavities prepared with
      Er,Cr:YSGG laser or bur in primary teeth.
AB  - OBJECTIVE: The purpose of this study was to analyze the resin-dentin interface in
      cavities prepared with laser or bur in primary teeth. BACKGROUND DATA: Erbium,
      chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser was expected to be an
      alternative cavity preparation method, enhancing surface alterations and
      producing morphological changes. METHODS: Twenty extracted primary molar teeth
      were divided to four groups according to one of four cavity preparation and
      pretreatment regimens: Er,Cr:YSGG laser (G1), Er,Cr:YSGG laser+acid-etching (G2),
      bur (G3), and bur+acid-etching (G4). After applying composite resin to the
      cavities, the teeth were sectioned. The resin-dentin interface was analyzed under
      scanning electron microscopy (SEM) and ion analysis was performed with SEM-energy
      dispersive X-ray spectroscopy (EDX) after immersion in ammoniacal silver nitrate
      solution. RESULTS: In G1 and 2, the surfaces were wavy, and in G3 and 4, the
      surfaces were smooth. Microcracks were seen in some of the lased cavities. In G1
      and 2, dentin tubules were exposed and there was lack of a smear layer. In G3,
      there were gaps and a smear layer in the resin-dentin interface, but no gaps or
      smear layer were observed in G4. In G2, the resin tags were increased, and some
      resin tags were broken in cavities, which were prepared with laser (G1 and 2).
      CONCLUSIONS: According to the results of this study, acid-etching was recommended
      after laser preparations, to have a better adhesion.

PMID- 23859752
TI  - Biaxial mechanical properties of the inferior vena cava in C57BL/6 and CB-17
      SCID/bg mice.
AB  - Multiple murine models have proven useful in studying the natural history of
      neovessel development in the tissue engineering of vascular grafts. Nevertheless,
      to better understand longitudinal changes in the biomechanics of such neovessels,
      we must first quantify native tissue structure and properties. In this paper, we
      present the first biaxial mechanical data for, and nonlinear constitutive
      modeling of, &QJ;the inferior vena cava from two models used in tissue
      engineering: wild-type C57BL/6 and immunodeficient CB-17 SCID/bg mice. Results
      show that inferior vena cava from the latter are significantly stiffer in the
      circumferential direction, both materially (as assessed by a stored energy
      function) and structurally (as assessed by the compliance), despite a lower
      intramural content of fibrillar collagen and similar wall thickness. Quantifying
      the natural history of neovessel development in different hosts could lead to
      increased insight into the mechanisms by which cells fashion and maintain
      extracellular matrix in order to match best the host stiffness while ensuring
      sufficient vascular integrity. 

PMID- 23859753
TI  - Optimizing treatment for patients with irritable bowel syndrome with
      constipation.

PMID- 23859754
TI  - Perspectives on irritable bowel syndrome: where have we been? Where are we now?
AB  - Irritable bowel syndrome is a chronic functional disorder with a complex etiology
      and multiple overlapping symptoms. Irritable bowel syndrome is characterized by
      long-lasting abdominal pain or discomfort, abnormal bowel habits and typically
      inadequate response to many of the available therapies. 

PMID- 23859755
TI  - Management of irritable bowel syndrome with constipation: a flexible approach to
      treating a complex condition with multiple symptoms.
AB  - Irritable bowel syndrome is a heterogeneous disease with a complex underlying
      pathophysiology and multiple symptoms - that is, clinical manifestation patterns.
      As such, management of irritable bowel syndrome requires a flexible approach
      tailored to the individual patient. This article reviews rational, evidence-based
      management strategy and treatment options for this variable condition. 

PMID- 23859756
TI  - Emerging receptor target in the pharmacotherapy of irritable bowel syndrome with
      constipation.
AB  - Preclinical experiments in rodent models have recently provided new information
      on the mechanisms underlying pain sensation in chronic visceral hypersensitivity,
      as well as insights into the mechanism of action of new drugs targeting abdominal
      pain in irritable bowel syndrome (IBS). This article describes the evidence base
      supporting the role of guanylate cyclase C (GC-C) activation in the modulation of
      gastrointestinal transit and, in particular, in visceral hypersensitivity. We
      propose that GC-C activation represents an important emerging target for
      pharmacotherapy in IBS with constipation (IBS-C), particularly given the recent
      regulatory approval of the GC-C agonist linaclotide as a treatment for IBS-C.
      More specifically, we address the following questions: "How is pain transmitted
      from the colon?"; "How is abdominal pain increased in IBS-C?"; "How can we reduce
      IBS-related abdominal pain - what drugs have been developed?"; "Does linaclotide
      reduce abdominal pain in animals and humans?"; and "How does linaclotide reduce
      abdominal pain?".

PMID- 23859757
TI  - How can we achieve relief of bowel and abdominal symptoms for patients with
      irritable bowel syndrome with constipation?
AB  - Current interventions for irritable bowel syndrome with constipation tend to
      target single symptoms of the disorder, with multiple symptom relief only
      achieved through the use of combinations of therapies. Hence, there remains an
      unmet need for well-tolerated and effective treatments for irritable bowel
      syndrome with constipation that target abdominal symptoms, including abdominal
      pain and bowel symptoms. 

PMID- 23859758
TI  - Genetic and cellular mechanisms regulating plant responses to necrotrophic
      pathogens.
AB  - Necrotrophs are plant pathogens that kill host cells and proliferate on nutrients
      from dead or dying tissues causing devastating diseases of horticultural and
      agronomic crops. Their interactions with plants involve a complex network of
      pathogen disease factors and corresponding plant immune response regulators.
      Mechanisms of quantitative resistance and the major regulators intersect
      regardless of pathogen life style. By contrast, some plant immune responses, such
      as effector-triggered immunity (ETI), a major source of qualitative resistance to
      biotrophs, are co-opted by necrotrophs to promote disease, which highlights the
      disparate plant immunity systems. Advances towards understanding mechanisms and
      processes underlying host responses to necrotrophs are summarized. 

PMID- 23859759
TI  - Angiopoietins in inflammation and their implication in the development of
      inflammatory bowel disease. A review.
AB  - BACKGROUND: Angiopoietins are essential angiogenic mediators. Since inflammatory
      bowel disease (IBD) involves inflammation, ulceration and regeneration of the
      intestinal mucosa, the angiopoietin system has been proposed as a factor to
      maintain pathological angiogenesis during the development of the IBD. AIM: To
      review the potential role of angiopoietins in the inflammation driven by
      angiogenesis during the course of the IBD. METHODS: Publications were identified
      by PubMed searches using the following key words: angiopoietin; Tie-2 receptor;
      angiogenesis; inflammatory bowel disease and inflammation, in various
      combinations. RESULTS: Angiopoietin-1 acts as a regulator of blood vessel
      maturation and has anti-inflammatory properties, whereas angiopoietin-2 marks the
      onset of angiogenesis and is required for normal formation of lymph vessels. Both
      angiopoietins make use of their angiogenic regulatory effects via the
      angiopoietin tyrosine-kinase receptor (Tie-2). While angiogenesis has been shown
      to promote and sustain many events of inflammation, the involvement of the
      angiopoietin system in IBD has been reported in few studies. It is not clear
      whether the angiopoietins' role in the development of intestinal inflammation is
      due to an imbalance in the levels of these proteins or this system exerts its pro
      angiogenic properties through a different mechanism during the close-loop
      relationship between angiogenesis and inflammation. CONCLUSIONS: Angiopoietins
      have key functions in the angiogenic process, and their abnormal activation might
      depend on their surrounding inflamed environment. The determination of these
      angiogenic factors in serum and tissue could be useful for monitoring IBD
      progression.

PMID- 23859760
TI  - Cellular uptake and transport of zein nanoparticles: effects of sodium caseinate.
AB  - Cellular evaluation of zein nanoparticles has not been studied systematically due
      to their poor redispersibility. Caseinate (CAS)-stabilized zein nanoparticles
      have been recently developed with better redispersibility in salt solutions. In
      this study, zein-CAS nanoparticles were prepared with different zein/CAS mass
      ratios. The prepared nanoparticles demonstrated good stabilities to maintain
      particle size (120-140 nm) in cell culture medium and HBSS buffer at 37  degrees
      C. The nanoparticles showed no cytotoxicity for Caco-2 cells for 72 h. CAS not
      only significantly enhanced cell uptake of zein nanoparticles in a concentration-
      and time-dependent manner but also remarkably improved epithelial transport
      through Caco-2 cell monolayer. The cell uptake of zein-CAS nanoparticles
      indicated an energy-dependent endocytosis process as evidenced by cell uptake
      under blocking conditions, that is, 4  degrees C, sodium azide, and colchicine.
      Fluorescent microscopy clearly showed the internalization of zein-CAS
      nanoparticles. This study may shed some light on the cellular evaluations of
      hydrophobic protein nanoparticles. 

PMID- 23859761
TI  - Amphiphilic oligoethyleneimine-beta-cyclodextrin "click" clusters for enhanced
      DNA delivery.
AB  - Monodisperse amphiphilic oligoethyleneimine (OEI)-beta-cyclodextrin (betaCD)
      clusters have been prepared, and their potential as gene delivery systems has
      been evaluated in comparison with a nonamphiphilic congener. The general
      prototype incorporates tetraethyleneimine segments linked to the primary rim of
      betaCD through either triazolyl or thioureidocysteaminyl connectors. Transfection
      efficiency data for the corresponding CD:pDNA nanocomplexes (CDplexes) in BNL-CL2
      murine hepatocytes evidenced the strong beneficial effect of facial
      amphiphilicity. 

PMID- 23859762
TI  - A new high affinity variant Hb Aurillac (beta141Leu->Val).
AB  - Hemoglobin (Hb) variant beta141(H19)Leu->Val (HBB:c.424C>G), one of the two
      mutations defining Hb Kochi [the other one being beta144(HC1)Lys-Tyr-His->0
      (HBB:c.433A>T)], was found as an isolated mutation. In contrast to what was
      suggested for Hb Kochi, the new variant was not clinically silent. It displayed
      increased oxygen affinity and was associated with mild erythrocytosis. 

PMID- 23859763
TI  - Effects of radiation on the incidence of prostate cancer among Nagasaki atomic
      bomb survivors.
AB  - Atomic bomb survivors have been reported to have an increased risk of some
      cancers, especially leukemia. However, the risk of prostate cancer in atomic bomb
      survivors is not known to have been examined previously. This study examined the
      association between atomic bomb radiation and the incidence of prostate cancer
      among male Nagasaki atomic bomb survivors. The subjects were classified by
      distance from the hypocenter into a proximal group (<2 km), a distal group (>=2
      km), and an early entrance group (those who entered the region <2 km from the
      hypocenter within 2 weeks after the explosion). Between 1996 and 2009, 631 new
      cases of prostate cancer were identified among approximately 18 400 male Nagasaki
      atomic bomb survivors who were alive in 1996. The Cox proportional hazard model
      was used to estimate the risk of prostate cancer development, with adjustment for
      age at atomic bomb explosion, attained age, smoking status, and alcohol
      consumption. Compared with the distal group, the proximal group had significant
      increased risks of total, localized, and high-grade prostate cancer (relative
      risk and 95% confidence interval: 1.51 [1.21-1.89]; 1.80 [1.26-2.57]; and 1.88
      [1.20-2.94], respectively). This report is the first known to reveal a
      significant relationship between atomic bomb radiation and prostate cancer.

PMID- 23859764
TI  - Muscle activity influence on the kinematics of the cervical spine in frontal
      tests.
AB  - OBJECTIVE: The question of muscle activity influence on the cervical spine
      kinematics during rear-end and frontal crash events has been discussed. Less data
      are available concerning frontal collisions. Therefore, the objective of this
      study was to investigate the influence of the ventral and dorsal neck muscles on
      the cervical spine kinematics during simulated frontal sled collisions. METHODS:
      A frontal collision with a velocity change (delta V) of 10.2 km/h was simulated
      in a sled test with 10 healthy subjects (7 female; 3 male). A high-speed camera
      and accelerometers recorded the motion and acceleration data. The activity of the
      sternocleidomastoid muscles was recorded with surface electrodes. To avoid cross
      talk, an intramuscular recording of the semispinalis capitis muscles was
      performed with fine-wire electrodes. RESULTS: The sequence of both muscle
      activities was reproducible in all subjects. The maximal force of the
      sternocleidomastoid muscle was observed after a median of 152 ms, with 0 defining
      the time of the trigger signal. With earlier onset of muscle force, maximal
      dorsal horizontal acceleration of the head (r = -0.600) was reached later and the
      ventral translation (r = -0.733) and flexion movement (r = -0.755) set in
      earlier. The maximal force of the semispinalis capitis muscle was observed after
      a median of 160 ms. If the duration of muscle force was longer, the maximal head
      flexion (r = 0.685) and the maximal ventral head translation (r = 0.738) were
      reached later. CONCLUSIONS: The sternocleidomastoid muscle force is mainly
      associated with the horizontal head acceleration and influences the onset of the
      flexion and translation motion. To summarize, these temporal correlations allow
      the conclusion that the semispinalis capitis muscle force is mainly associated
      with the angular head acceleration and influences the duration of the flexion and
      translation motion.

PMID- 23859765
TI  - A new impact factor and new directions for ACS Chemical Neuroscience.

PMID- 23859766
TI  - Apelin administration ameliorates high fat diet-induced cardiac hypertrophy and
      contractile dysfunction.
AB  - Apelin has been recognized as an adipokine that plays an important role in
      regulating energy metabolism and is credited with antiobesity and antidiabetic
      properties. This study was designed to examine the effect of exogenous apelin on
      obesity-associated cardiac dysfunction. Oral glucose tolerance test,
      echocardiography, cardiomyocyte contractile and intracellular Ca(2+) properties
      were assessed in adult C57BL/6J mice fed - low or a - high-fat diet for 24weeks
      followed by apelin treatment (100nmol/kg, i.p. for 2weeks). High-fat diet
      resulted in increased left ventricular diastolic and systolic diameters, and wall
      thickness, compromised fractional shortening, impaired cardiomyocyte mechanics
      (peak-shortening, maximal velocity of shortening/relengthening, and duration of
      shortening and relengthening) and compromised intracellular Ca(2+) handling, all
      of which were reconciled by apelin. Apelin treatment also reversed high fat diet
      induced changes in intracellular Ca(2+) regulatory proteins, ER stress, and
      autophagy. In addition, microRNAs (miR) -133a, miR-208 and miR-1 which were
      elevated following high-fat feeding were attenuated by apelin treatment. In
      cultured cardiomyocytes apelin reconciled palmitic acid-induced cardiomyocyte
      contractile anomalies. Collectively, these data depict a pivotal role of apelin
      in obesity-associated cardiac contractile dysfunction, suggesting a therapeutic
      potential of apelin in the management of cardiac dysfunction associated with
      obesity. 

PMID- 23859767
TI  - Untangling regulatory networks to spot drivers and modulators of cardiac disease.

PMID- 23859768
TI  - A brief intervention affects parents' attitudes toward using less physical
      punishment.
AB  - Consecutive English and Spanish speaking caregivers of 6-24 month old children
      were randomly assigned to either a control or intervention group. Parents in the
      intervention group were instructed to view at least 4 options to discipline a
      child in an interactive multimedia program. The control group participants
      received routine primary care with their resident physician. After the clinic
      visit, all parents were invited to participate in a research study; the
      participation rate was 98% (258/263). The key measure was the Attitudes Toward
      Spanking (ATS) scale. The ATS is correlated with parents' actual use of physical
      punishment. Parents with higher scores are more likely to use physical punishment
      to discipline their children. Parents in the intervention group had an ATS score
      that was significantly lower than the ATS score of parents in the control group
      (median=24.0, vs. median=30; p=0.043). Parents in the control group were 2 times
      more likely to report that they would spank a child who was misbehaving compared
      with parents in the intervention group (16.9% vs. 7.0%, p=0.015). In the short
      term, a brief intervention, integrated into the primary care visit, can affect
      parents' attitudes toward using less physical punishment. It may be feasible to
      teach parents to not use physical punishment using a population-based approach.
      The findings have implications for how to improve primary care services and the
      prevention of violence. 

PMID- 23859769
TI  - An ounce of prevention or two... providing anticipatory guidance regarding
      personal space and privacy. A commentary.

PMID- 23859770
TI  - Influence of sleep deprivation on expression of MKK4 and c-fos in the mandibular
      condylar cartilage of rats.
AB  - The aim of this study was to investigate the changes in expression of mitogen
      activated protein kinase kinase 4 (MKK4) and c-fos in the mandibular condylar
      cartilage of rats that had been subjected to sleep deprivation. One hundred and
      twenty female Wistar rats were randomly divided into 6 groups with 20 in each:
      sleep deprivation for 2 days, 4 days, 6 days, and 8 days, large-platform
      controls, and cage controls. After sleep deprivation by the modified multiple
      platform method the sleep-deprived rats were killed. The large-platform and cage
      control rats were killed at the same time as the rats deprived of sleep for 8
      days. Haematoxylin and eosin were used to record the morphological changes in
      cartilage, and immunohistochemistry and real-time quantitative polymerase chain
      reaction (PCR) were used to detect the expression of MKK4 and c-fos. Pathological
      alterations were apparent after 6 and 8 days of sleep deprivation. Compared with
      control groups, the expression of MKK4 in the sleep-deprived groups was lower,
      while that of c-fos was higher. As the duration of sleep deprivation increased,
      the expression of MKK4 decreased. These results indicate that the variation in
      expression of MKK4 and c-fos may be correlated with pathological changes induced
      by sleep deprivation in mandibular condylar cartilage in rats. 

PMID- 23859771
TI  - Clinical validation of nursing diagnosis "parental role conflict" in mothers of
      hospitalized newborns.
AB  - OBJECTIVE: To clinically validate the nursing diagnosis, parental role conflict,
      in mothers of hospitalized newborns. METHOD: Fehring's Clinical Validation Model
      was used, focusing on mothers, using a sample of 83. Major defining
      characteristics have been defined as the main indicators of the presence of a
      diagnosis, whereas minor are secondary indicators. RESULTS: Four minor defining
      characteristics were identified: (a) "anxiety," (b) "expresses concerns about
      changes in maternal role," (c) "expresses concerns about family," and (d) "fear."
      Major defining characteristics did not occur. CONCLUSION: Mothers who spent less
      time with their infants were the ones that presented a major number of defining
      characteristics; therefore, they should have more opportunities for being with
      their babies. Other studies on subjective phenomena are needed.

PMID- 23859773
TI  - Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in
      Alzheimer's disease brains.
AB  - There is a high demand for the development of an imaging agent for
      neurofibrillary tangles (NFTs) detection in Alzheimer's diagnosis. In the present
      study, a series of rhodanine-3-acetic acids was synthesized and evaluated for
      fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven
      probes have shown excellent binding affinity to NFTs over amyloid plaques in the
      Thiazine red R displacement assay. However, the selectivity in this in vitro
      assay is not confirmed by the histopathological evaluation, which indicates
      significant differences in the binding sites in the assays. Probe 6 showed
      binding affinity (IC50=19nM) to tau aggregates which is the highest among this
      series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100nM to tau
      aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these
      five probes with human liver carcinoma cells revealed that these compounds excert
      negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed
      negligible cytotoxicity at 24 and 72h post fertilization. 

PMID- 23859772
TI  - Molecular tension sensors report forces generated by single integrin molecules in
      living cells.
AB  - Living cells are exquisitely responsive to mechanical cues, yet how cells produce
      and detect mechanical force remains poorly understood due to a lack of methods
      that visualize cell-generated forces at the molecular scale. Here we describe
      Forster resonance energy transfer (FRET)-based molecular tension sensors that
      allow us to directly visualize cell-generated forces with single-molecule
      sensitivity. We apply these sensors to determine the distribution of forces
      generated by individual integrins, a class of cell adhesion molecules with
      prominent roles throughout cell and developmental biology. We observe strikingly
      complex distributions of tensions within individual focal adhesions. FRET values
      measured for single probe molecules suggest that relatively modest tensions at
      the molecular level are sufficient to drive robust cellular adhesion. 

PMID- 23859774
TI  - 5-Substituted-(1,2,3-triazol-4-yl)thiophene-2-sulfonamides strongly inhibit human
      carbonic anhydrases I, II, IX and XII: solution and X-ray crystallographic
      studies.
AB  - We report here a series of 2-thiophene-sulfonamides incorporating 1-substituted
      aryl-1,2,3-triazolyl moieties, prepared by click chemistry from 5
      ethynylthiophene-2-sulfonamide and substituted aryl azides. The new sulfonamides
      were investigated as inhibitors of the zinc metalloenzyme CA (EC 4.2.1.1), and
      more specifically against the human (h) cytosolic isoforms hCA I and II and the
      transmembrane, tumor-associated ones hCA IX and XII: The new compounds were
      medium-weak hCA I inhibitors (KIs in the range of 224-7544nM), but were
      compactly, highly effective, low nanomolar hCA II inhibitors (KIs of 2.2-7.7nM).
      The tumor-associated hCA IX was inhibited with KIs ranging between 5.4 and 811nM,
      whereas hCA XII with inhibition constants in the range of 3.4-239nM. The X-ray
      crystal structure of the adducts of two such compounds bound to hCA II (one
      incorporating 1-naphthyl, the other one 3-cyanophenyl moieties) evidenced the
      reasons of the high affinity for hCA II. Highly favorable, predominantly
      hydrophobic interactions between the sulfonamide scaffold and the hCA II active
      site were responsible for the binding, in addition to the coordination of the
      sulfamoyl moiety to the zinc ion. The tails of the two inhibitors adopted very
      diverse orientations when bound to the active site, with the naphthyltriazolyl
      moiety orientated towards the hydrophobic half of the active site, and the 3
      cyanophenyl one pointing towards the hydrophilic half. These data may be used for
      the structure-based drug design of even more effective hCA II inhibitors, with
      potential use as antiglaucoma agents or as diuretics. 

PMID- 23859775
TI  - Liver-targeting of primaquine-(poly-gamma-glutamic acid) and its degradation in
      rat hepatocytes.
AB  - We have synthesized poly-gamma-glutamic acid (PGA) modified with a synthetic
      trivalent glyco-ligand (TriGalNAc) for the hepatocyte asialoglycoprotein receptor
      (ASGP-R). We investigated in vivo distribution of unmodified PGA and TriGalNAc
      modified PGA (TriGalNAc-PGA) in mice after intravenous injection. Most of
      unmodified PGA administered was transported to the bladder over 20-80min,
      suggesting a rapid excretion of unmodified PGA into urine. In contrast, TriGalNAc
      PGA was found exclusively in the liver over the same period of time. We further
      synthesized TriGalNAc-PGA-primaquine conjugate (TriGalNAc-PGA-PQ), and
      investigated binding, uptake, and catabolism of the conjugate by rat hepatocytes.
      Our studies indicated that approximately 250ng per million cells of the conjugate
      bound to one million rat hepatocytes at 0 degrees C, and approximately 2MUg per
      million cells of the conjugate was taken up over 7h incubation at 37 degrees C.
      Furthermore, our results suggested that TriGalNAc-PGA-PQ was almost completely
      degraded over 24h, and small degradation products were secreted into cell culture
      medium. The results described in this report suggest that the TriGalNAc ligand
      can serve as an excellent targeting device for delivery of PGA-conjugates to the
      liver hepatocytes, and rat hepatocytes possess sufficient capacity to digest PGA
      even modified with other substituents. 

PMID- 23859776
TI  - Improved synthesis of 17beta-hydroxy-16alpha-iodo-wortmannin, 17beta-hydroxy
      16alpha-iodoPX866, and the [(131)I] analogue as useful PET tracers for PI3
      kinase.
AB  - An improved method for the synthesis of 17beta-hydroxy-16alpha-iodo-wortmannin
      along with the first synthesis of 17beta-hydroxy-16alpha-iodoPX866 and [(131)I]
      radiolabeled 17beta-hydroxy-16alpha-[(131)I]iodo-wortmannin, as potential PET
      tracers for PI3K was also described. The differences between wortmannin and its
      iodo analogue were compared by covalently docking each structure to L833 in PI3K.

PMID- 23859777
TI  - Synthesis and biological evaluation of novobiocin analogues as potential heat
      shock protein 90 inhibitors.
AB  - Recent studies have shown that novobiocin (NB), a member of the coumermycin (CA)
      family of antibiotics with demonstrated DNA gyrase inhibitory activity, inhibits
      Heat shock protein 90 (HSP90) by binding weakly to a putative ATP-binding site
      within its C-terminus. To develop more potent HSP90 inhibitors that target this
      site and to define structure-activity relationships (SARs) for this class of
      compounds, we have synthesized twenty seven 3-amido-7-noviosylcoumarin analogues
      starting from NB and CA. These were evaluated for evidence of HSP90 inhibition
      using several biological assays including inhibition of cell proliferation and
      cell cycle arrest, induction of the heat shock response, inhibition of luciferase
      refolding in vitro, and depletion of the HSP90 client protein c-erbB-2/HER-2/neu
      (HER2). This SAR study revealed that a substantial increase in biological
      activity can be achieved by introduction of an indole-2-carboxamide group in
      place of 4-hydroxy-isopentylbenzamido group at C-3 of NB in addition to
      removal/derivatization of the 4-hydroxyl group from the coumarin ring.
      Methylation of the 4-hydroxyl group in the coumarin moiety moderately increased
      biological activity as shown by compounds 11 and 13. Our most potent new analogue
      19 demonstrated biological activities consistent with known HSP90-binding agents,
      but with greater potency than NB. 

PMID- 23859778
TI  - 2-Substituted 4-hydroxybutanamides as potential inhibitors of gamma-aminobutyric
      acid transporters mGAT1-mGAT4: synthesis and biological evaluation.
AB  - A series of 2-substituted 4-hydroxybutanamide derivatives has been synthesized by
      the aminolysis of appropriate 2-substituted dihydrofuran-2(3H)-one derivatives
      with various substituted benzylamines. The final compounds have been evaluated
      for their capability of inhibiting the GABA transport proteins GAT1-4 stably
      expressed in HEK-239 cell lines. The pIC50 values determined were in the range
      4.21-5.14. Two compounds (16a and 16d), which displayed the most interesting
      profiles in in vitro tests, have also been subjected to further preliminary
      behavioral studies, evaluating their antinociceptive activity in hot-plate,
      writhing, and formalin tests. Their influence on motor coordination has also been
      assessed. 

PMID- 23859779
TI  - Synthesis and initial in vitro biological evaluation of two new zinc-chelating
      compounds: comparison with TPEN and PAC-1.
AB  - The lipophilic, cell-penetrating zinc chelator N,N,N',N',-tetrakis(2
      pyridylmethyl) ethylenediamine (TPEN, 1) and the zinc chelating procaspase
      activating compound PAC-1 (2) both have been reported to induce apoptosis in
      various cell types. The relationship between apoptosis-inducing ability and zinc
      affinity (Kd), have been investigated with two new model compounds, ZnA-DPA (3)
      and ZnA-Pyr (4), and compared to that of TPEN and PAC-1. The zinc-chelating o
      hydroxybenzylidene moiety in PAC-1 was replaced with a 2,2'-dipicoylamine (DPA)
      unit (ZnA-DPA, 3) and a 4-pyridoxyl unit (ZnA-Pyr, 4), rendering an order of zinc
      affinity TPEN>ZnA-Pyr>ZnA-DPA>PAC-1. The compounds were incubated with the rat
      pheochromocytoma cell line PC12 and cell death was measured in combination with
      ZnSO4, a caspase-3 inhibitor, or a ROS scavenger. The model compounds ZnA-DPA (3)
      and ZnA-Pyr (4) induced cell death at higher concentrations as compared to PAC-1
      and TPEN, reflecting differences in lipophilicity and thereby cell-penetrating
      ability. Addition of ZnSO4 reduced cell death induced by ZnA-Pyr (4) more than
      for ZnA-DPA (3). The ability to induce cell death could be reversed for all
      compounds using a caspase-3-inhibitor, and most so for TPEN (1) and ZnA-Pyr (4).
      Reactive oxygen species (ROS), as monitored using dihydro-rhodamine (DHR), were
      involved in cell death induced by all compounds. These results indicate that the
      Zn-chelators ZnA-DPA (3) and ZnA-Pyr (4) exercise their apoptosis-inducing effect
      by mechanisms similar to TPEN (1) and PAC-1 (2), by chelation of zinc, caspase-3
      activation, and ROS production. 

PMID- 23859780
TI  - Cembrane diterpenoids from the soft coral Sarcophyton trocheliophorum Marenzeller
      as a new class of PTP1B inhibitors.
AB  - A detailed investigation of the South China Sea soft coral Sarcophyton
      trocheliophorum Marenzeller yielded, along with six known terpenes (6-11), the
      new sarcophytonolides N-R (1-5), whose structures have been elucidated by
      detailed spectroscopic analysis. Sarcophytonolides N-R are mono- or bicyclic
      cembranoids characterized by the presence of three/four double bonds and oxidized
      methyl groups. Some of the isolated compounds showed significant inhibitory
      activity against human protein tyrosine phosphatase 1B (PTP1B) enzyme, a key
      target for the treatment of type-II diabetes and obesity, and some preliminary
      structure-activity relationships have been drawn. This is the first report on the
      anti-PTP1B activity of cembrane diterpenoids. 

PMID- 23859781
TI  - Uptake of arsenic species by turnip (Brassica rapa L.) and lettuce (Lactuca
      sativa L.) treated with roxarsone and its metabolites in chicken manure.
AB  - Roxarsone is an organoarsenic feed additive that can be metabolised to other
      higher toxic arsenic (As) species in animal manure such as arsenate, arsenite,
      monomethylarsonic acid, dimethylarsinic acid, 3-amino-4-hydroxyphenylarsonic acid
      and other unknown As species. The accumulation, transport and distribution of As
      species in turnip (Brassica rapa L.) and lettuce (Lactuca sativa L.) amended with
      roxarsone and its metabolites in chicken manure were investigated. Results showed
      arsenite was the predominant As form, followed by arsenate in turnip and lettuce
      plants, and a low content of dimethylarsinic acid was detected only in lettuce
      roots. Compared with the control plants treated with chicken manure without
      roxarsone and its metabolites, the treatments containing roxarsone and its
      metabolites increased arsenite content by 2.0-3.2% in turnip shoots, by 6.6-6.7%
      in lettuce shoots, by 11-44% in turnip tubers and by 18-20% in lettuce roots at
      two growth stages. The enhanced proportion of arsenate content in turnip shoots,
      turnip tubers and lettuce roots was 4.3-14%, 20-35% and 70%, respectively, while
      dimethylarsinic acid content in lettuce roots increased 2.4 times. Results showed
      that the occurrence of dimethylarsinic acid in lettuce roots might be converted
      from the inorganic As species and the uptake of both inorganic and organic As
      compounds in turnip and lettuce plants would be enhanced by roxarsone and its
      metabolites in chicken manure. The pathway of roxarsone metabolites introduced
      into the human body via roxarsone -> animal -> manure -> soil -> crop was
      indicated. 

PMID- 23859782
TI  - The expression and localization of LRF in the female reproductive tract of
      cycling mice throughout the estrous cycle.
AB  - In this article, the expression patterns of LRF in the mouse oviduct, uterus, and
      ovary were checked during estrous cycle. The expression of LRF mRNA and protein
      were remarkably changed in the ovary, oviduct, and uterus at four phases. LRF
      immunostaining was detected in the follicle from primary to antral follicle,
      luminal and glandular epithelial cells of the uterus, and cilia of the ciliated
      cells of the oviduct at all phase. Our findings suggested that LRF may be related
      to the processes of development and maturation of oocyte, gamete transport, and
      the development of early embryo. 

PMID- 23859783
TI  - Antibody labeling with Remazol Brilliant Violet 5R, a vinylsulphonic reactive
      dye.
AB  - Colloidal gold is the first choice for labeling antibodies to be used in Point Of
      Care Testing. However, there are some recent reports on a family of textile dyes
      named "reactive dyes"-being suitable for protein labeling. In the present
      article, protein labeling conditions were optimized for Remazol Brilliant Violet
      5R, and the sensitivity of the labeled antibodies was assessed and compared with
      that of colloidal-gold labeled antibodies. Also, the accelerated stability was
      explored. Optimal conditions were pH 10.95, dye:Ab molar ratio of 264 and an
      incubation time of 132 min. Labeled antibodies were stable, and could be
      successfully used in a slot blot assay, detecting as low as 400 ng/mL. Therefore,
      the present work demonstrates that vinylsulphonic reactive dyes can be
      successfully used to label antibodies, and are excellent candidates for the
      construction of a new generation of Point of Care Testing kits.

PMID- 23859784
TI  - Differential modulation of phenotypic composition of HIV-infected and -uninfected
      PBMCs during cryopreservation.
AB  - This article was designed to determine variations in phenotypic composition of
      fresh and frozen PBMCs for assessing utility of cryopreserved PBMCs for
      phenotypic assays. Relative percentages of effector memory cells increased
      significantly as against percentages of naive cells which showed significant
      decrease after cryopreservation in HIV-uninfected samples. These differences were
      not significant in HIV-infected individuals. There was no significant difference
      in the expression of activation markers in fresh and frozen PBMCs except the HLA
      DR expression on CD8 cells in HIV-infected individuals, which was significantly
      decreased in frozen PBMCs. Thus, cryopreservation resulted in differential effect
      on phenotypic composition of PBMCs in HIV-infected and -uninfected individuals. 

PMID- 23859785
TI  - Detection of anti-SP100 antibodies in primary biliary cirrhosis. Comparison of
      ELISA and immunofluorescence.
AB  - Primary biliary cirrhosis (PBC) is, which a chronic, autoimmune liver disease.
      Some patients have antinuclear antibodies anti-Sp100, which are considered to be
      disease-specific. We compared an enzyme-linked immunosorbent assay (ELISA) and
      indirect immunofluorescence (IIF) for detection of anti-Sp100. The sensitivity of
      anti-Sp100 determined by ELISA and IIF was 44% and 34%, respectively. Specificity
      was 99% for ELISA and 98% for IIF, respectively. The positive and negative
      predictive value (PPV, NPV) for anti-Sp100 determined by ELISA were 98%, 60% and
      95%, 56% for IIF respectively. IIF required substantial experience in
      interpreting subjective patterns, whereas ELISA was more sensitive, cheaper, less
      time consuming, and produced clear-cut quantitative results. 

PMID- 23859786
TI  - The presence of RANKL-OPG complex in human osteosarcoma U2OS.
AB  - A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for the human
      receptor activator of nuclear factor kappaB (RANKL)-osteoprotegerin (OPG) complex
      was developed by utilizing a monoclonal antibody that recognizes human soluble
      RANKL as an immobilized capture component and biotinylated human OPG polyclonal
      antibody. We could quantify the RANKL-OPG complex level (detection limit: 100
      pg/mL). Employing this assay system, we demonstrated that the RANKL-OPG complex
      was constitutively present in the conditioned medium of human osteoblastic
      sarcoma U2OS, although the complex was not detectable in other human osteoblastic
      sarcoma cell line, MG-63, HOS, and SaOS-2. 

PMID- 23859787
TI  - A sensitive time-resolved fluoroimmunoassay for determination of median levels of
      pregnancy-associated plasma protein a in pregnant women in China.
AB  - Pregnancy-associated plasma protein A (PAPP-A) is an important serum marker for
      first trimester screening. Its weekly median value varies with ethnicity. A one
      step time-resolved fluoroimmunoassay (TRFIA) using two monoclonal antibodies
      against PAPP-A with Eu(3+) chelates as labels has been developed. Using the assay
      described here, we evaluated 5,301 normal serum samples from Chinese women at 7
      13 weeks of gestation. The detection limit using this assay was 1.2 mIU/L, and
      the maximum detection range was up to 10,000 mIU/L. The intra-assay and inter
      assay coefficients of variation were <3.0% and <5.0%, respectively, and the mean
      recovery rate was 98.0%. PAPP-A concentrations measured in 516 maternal serum
      samples correlated well with those obtained by Dissociation-Enhanced Lanthanide
      Fluorescent Immunoassay (DELFIA) PAPP-A assay (r=0.988, P<0.001). The medians for
      7-13 weeks of maternal serum PAPP-A were higher in the women from China compared
      to reports from other countries. The present assay possesses accuracy and high
      sensitivity and exhibits great potential for the clinical analysis of PAPP-A. Our
      investigation on the median concentrations of PAPP-A will help establish
      reference values that are specific for China and study the importance of ethnic
      factors in biochemical screening.

PMID- 23859788
TI  - Peroxidase-linked assay for detection of antibodies against bovine leukosis
      virus.
AB  - A peroxidase linked assay (PLA) was designed to screen bovine sera for the
      presence of specific antibodies against bovine leukosis virus (BLV). Out of 201
      samples of bovine sera analyzed, 52.2% were considered positive by PLA, 26.4% by
      AGID, and 38.9% by ELISA. Western blotting analyses excluded 27 samples found to
      be positive by PLA. PLA showed 100% of sensitivity when compared with AGID and
      ELISA. Specificity was 64.8% and 78%, respectively (kappa coefficients were 0.70
      and 0.83). These findings indicate that PLA can be used as an alternative method
      for the diagnosis of BLV infection in cattle. 

PMID- 23859789
TI  - Detection of antibodies to the 20s proteasome by ELISA.
AB  - The presence of antibodies against the 20S proteasome has been correlated with
      diseases like multiple sclerosis (MS) and systemic lupus erythematosus (SLE) but
      no definite association has been established. In order to investigate this
      further, we optimized an ELISA for proteasome antibodies and applied it to test a
      total of 324 serum and plasma samples from MS patients, SLE patients, and healthy
      controls. Our results yield a functional and reliable assay but no correlation
      between the amount of proteasome antibodies present and the development of MS or
      SLE could be established. 

PMID- 23859790
TI  - Enzyme-linked Fab' fragment based competitive immunoassay for ovalbumin in hot
      processed food.
AB  - A hen's egg is one of the most common causes of food allergy. The allergen
      quantitation in hot-processed food is always a difficult task, because the
      protein in these samples will be denatured, insoluble, and degraded. This article
      presents a competitive enzyme linked immunosorbent assay (ELISA) for the
      quantitation of ovalbumin in hot-processed food. Its recovery was improved nearly
      two times by the assay method as compared with previous sandwich ELISA. The heat
      and DL-Dithiothreitol treated ovalbumin was used as antigen for monoclonal
      antibody preparation. A smaller labeled antibody molecule, horseradish peroxidase
      (HRP) labeled Fab' fragment, was used to replace IgG in ELISA for improving
      sensitivity and analytical speed of the method. A binding site protection
      procedure was developed for Fab' fragment labeling with HRP, which prevented
      damage to the Fab' binding site. The combination and separation steps were
      efficiently completed in an affinity spin column. Based on the optimized ELISA
      condition, the IC50 was 1.2 ug/mL and the coefficients of variation were less
      than 10%.

PMID- 23859791
TI  - Comparative evaluation of ELISA and dot-blot for the diagnosis of tuberculous
      meningitis.
AB  - Tuberculous meningitis is a central nervous system tuberculosis caused by M.
      tuberculosis. It causes high mortality if delayed in diagnosis and treatment. In
      this comparative study, Cerebrospinal fluid from TBM and non TBM patients were
      analyzed by ELISA and Dot-blot for anti-tuberculous antibodies. About 70% of the
      TBM samples showed positivity by Dot-blot and 72.5% by ELISA. Among the non TBM
      controls, 2.9% showed positivity by Dot-blot and 4.4% by ELISA. Both methods did
      not differ significantly as seen by Fisher's exact test (p = 0.50). Thus, Dot
      blot could be an easy alternative to ELISA for quick diagnosis of TBM.

PMID- 23859792
TI  - Monoclonal antibodies requiring coating buffer with low pH for efficient antigen
      capture in sandwich ELISA: the rarities or practically important phenomena?
AB  - This article reexamines some opinions concerning pH requirements for optimal
      immobilization of monoclonal antibodies (mAbs) by passive adsorption in antigen
      capture ELISA. It was discovered that substitution of "classical" sodium
      phosphate (pH 7.5) and carbonate (pH 9.5) coating solutions by acid (pH 2.8)
      buffers maximized antigen capture 4 out of 10 different tested anti-HBsAg mAbs,
      resulting in a 1.5-2.5 increase of binding curve coefficients. By measuring both
      mAbs amounts and functionality, the enhancement effect was attributed to the
      better preservation of solid phase antibodies activity. 

PMID- 23859793
TI  - Establishment of a competitive ELISA for detection of florfenicol antibiotic in
      food of animal origin.
AB  - Florfenicol (FF) is a synthetic antibiotic with a broad antibacterial spectrum
      and the high therapeutic effectiveness that has been developed specifically for
      veterinary use. Obviously, FF adulterated in animal supplies is one of essential
      global concerns. A competitive ELISA for the detection of florfenicol in food of
      animal origin (swine, chicken, and fish) is described. Influence of
      immunoconjugate structure on the assay sensitivity and specificity was
      investigated. The new ELISA showed much lower than the MRPLs for FF at 100-3,000
      mg kg(-1) in the European Communities and the sensitivity of our ELISA method was
      superior to that described in other reports. According to the test preparation
      record, the limit of detection of the developed ELISA performed on meat species
      was 0.3 ug kg(-1) (IC50 value 1.9 ug kg(-1)). The method developed permits FF
      concentrations to be determined in the range 0.3-24.3 ug kg(-1). A low cross
      reactivity with florfenicol amine (FFA), thiamphenicol (TAP), and chloramphenicol
      (CAP) was displayed (16.2%, 9.5%, and 9.4%, respectively). Recovery in different
      food samples (swine, chicken, and fish) averages between 87-115%. The method can
      be applied for inspection of animal supplies for trace florfenicol residues.

PMID- 23859795
TI  - Statement of removal.

PMID- 23859796
TI  - Factors influencing the separation of oligonucleotides using reversed-phase/ion
      exchange mixed-mode high performance liquid chromatography columns.
AB  - New mixed-mode columns consisting of reversed-phase and ion-exchange separation
      modes were evaluated for the analysis of short RNA oligonucleotides (~20mers).
      Conventional analysis for these samples typically involves using two
      complementary methods: strong anion-exchange liquid chromatography (SAX-LC) for
      separation based on charge, and ion-pair reversed-phase liquid chromatography (IP
      RPLC) for separation based on hydrophobicity. Recently introduced mixed-mode high
      performance liquid chromatography (HPLC) columns combine both reversed-phase and
      ion-exchange modes, potentially offering a simpler analysis by combining the
      benefits of both separation modes into a single method. Analysis of a variety of
      RNA oligonucleotide samples using three different mixed-mode stationary phases
      showed some distinct benefits for oligonucleotide separation and analysis. When
      using these mixed-mode columns with typical IP-RPLC mobile phase conditions, such
      as ammonium acetate or triethylammonium acetate as the primary ion-pair reagent,
      the separation was mainly based on the IP-RPLC mode. However, when changing the
      mobile phase conditions to those more typical for SAX-LC, such as salt gradients
      with NaCl or NaBr, very different separation patterns were observed due to mixed
      mode interactions. In addition, the Scherzo SW-C18 and SM-C18 columns with sodium
      chloride or sodium bromide salt gradients also showed significant improvements in
      peak shape. 

PMID- 23859797
TI  - Thermal desorption-gas chromatography-mass spectrometry method to determine
      phthalate and organophosphate esters from air samples.
AB  - A method based on thermal desorption-gas chromatography-mass spectrometry (TD-GC
      MS) has been developed to determine four organophosphate esters, seven phthalate
      esters, and bis(2-ethylhexyl) adipate in the gas phase from harbour and urban air
      samples. The method involves the sampling of 1.5L of air in a Tenax TA sorbent
      tube followed by thermal desorption (using a Tenax TA cryogenic trap) coupled to
      gas chromatography-mass spectrometry. The repeatability of the method expressed
      as %RSD (n=3) is less than 15% and the MQLs are between 0.007MUgm(-3) (DMP, TBP,
      BBP, TPP and DnOP) and 6.7MUgm(-3) (DEHP). The method was successfully applied in
      two areas (urban and harbour) testing two and three points in each one,
      respectively. Some of these compounds were found in both urban and harbour
      samples. Di-(2-ethylhexyl)phthalate was the most abundant compound found in both
      areas at concentration levels between 6.7MUgm(-3) and 136.4MUgm(-3). This study
      demonstrates that thermal desorption is an efficient method for the determination
      of these semi-volatile compounds in the gas phase fraction of air samples. 

PMID- 23859798
TI  - Characterization of a large glycoprotein proteoglycan by size-exclusion
      chromatography combined with light and X-ray scattering methods.
AB  - The molecular weight and chain conformation of a proteoglycan derived from shark
      cartilage in solution were characterized by size-exclusion chromatography
      combined with low-angle laser light scattering and small-angle X-ray scattering
      methods. The total molecular weight of the proteoglycan was 3.9+/-0.2 million and
      the molecular weight of the main component was about 2.0+/-0.2 million. The X-ray
      scattering data revealed that the main components of the proteoglycan are nearly
      equal to a chain with excluded volume and their persistence lengths range from
      13.5 to 16.4nm. These results show that size-exclusion chromatography combined
      with low-angle laser light scattering and small-angle X-ray scattering
      measurements are complementarily useful for characterization of large biopolymers
      in solution. 

PMID- 23859800
TI  - Physiology of incretins and loss of incretin effect in type 2 diabetes and
      obesity.
AB  - An important role in the regulation of glucose homeostasis is played by
      incretins, which are gut-derived hormones released in response to nutrient
      ingestion. In humans, the major incretin hormones are glucagon-like peptide (GLP)
      1 and glucose-dependent insulinotropic polypeptide (GIP), and together they fully
      account for the incretin effect (that is, higher insulin release in response to
      an oral glucose challenge compared to an equal intravenous glucose load). Studies
      have shown that GLP-1 and GIP levels and actions may be perturbed in disease
      states, and the loss of incretin effect is likely to contribute importantly to
      the postprandial hyperglycaemia in type 2 diabetes. However, the specific cause
      effect relationship between disease and incretins is still unclear. This review
      focuses on several key studies elucidating the association of defective incretin
      action with obesity and T2DM and the effects of metformin and other anti-diabetic
      agents on the incretin system.

PMID- 23859799
TI  - Proximal inhibition of p38 MAPK stress signaling prevents distal axonopathy.
AB  - The p38 mitogen-activated protein kinase (MAPK) isoforms are phosphorylated by a
      variety of stress stimuli in neurodegenerative disease and act as upstream
      activators of myriad pathogenic processes. Thus, p38 MAPK inhibitors are of
      growing interest as possible therapeutic interventions. Axonal dysfunction is an
      early component of most neurodegenerative disorders, including the most prevalent
      optic neuropathy, glaucoma. Sensitivity to intraocular pressure at an early stage
      disrupts anterograde transport along retinal ganglion cell (RGC) axons to
      projection targets in the brain with subsequent degeneration of the axons
      themselves; RGC body loss is much later. Here we show that elevated ocular
      pressure in rats increases p38 MAPK activation in retina, especially in RGC
      bodies. Topical eye-drop application of a potent and selective inhibitor of the
      p38 MAPK catalytic domain (Ro3206145) prevented both the degradation of
      anterograde transport to the brain and degeneration of axons in the optic nerve.
      Ro3206145 reduced in the retina phosphorylation of tau and heat-shock protein 27,
      both down-stream targets of p38 MAPK activation implicated in glaucoma, as well
      as expression of two inflammatory responses. We also observed increased p38 MAPK
      activation in mouse models. Thus, inhibition of p38 MAPK signaling in the retina
      may represent a therapeutic target for preventing early pathogenesis in optic
      neuropathies. 

PMID- 23859801
TI  - Development of lacosamide for the treatment of partial-onset seizures.
AB  - Lacosamide is an antiepileptic drug (AED) available in multiple formulations that
      was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS)
      in adults. Unlike traditional sodium channel blockers affecting fast
      inactivation, lacosamide selectively enhances sodium channel slow inactivation.
      This mechanism of action results in stabilization of hyperexcitable neuronal
      membranes, inhibition of neuronal firing, and reduction in long-term channel
      availability without affecting physiological function. Lacosamide has a well
      characterized and favorable pharmacokinetic profile, including a fast absorption
      rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low
      potential for drug-drug interactions. Lacosamide clinical development included
      three placebo-controlled, double-blind, randomized trials conducted in more than
      1300 patients, each demonstrating safety and efficacy of lacosamide compared to
      placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide
      may broaden, pending results of trials evaluating its use as monotherapy for POS
      in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive
      treatment for uncontrolled primary generalized tonic-clonic seizures in those
      with idiopathic generalized epilepsy. 

PMID- 23859802
TI  - Development of boceprevir: a first-in-class direct antiviral treatment for
      chronic hepatitis C infection.
AB  - The identification of hepatitis C virus (HCV) as the causative agent of non-A and
      non-B hepatitis, over 20 years ago, fueled an intensive effort to develop direct
      acting antivirals targeting the viral polymerase and protease, two key proteins
      critical for HCV replication. However, it took more than two decades for these
      efforts to be realized with boceprevir, one of the two HCV protease inhibitors
      approved for treatment of HCV infection in 2011. The development of boceprevir is
      a major advancement in the ability to treat HCV infection and a significant step
      toward the long-term goal of eradicating chronic HCV infection. Both as a first
      in-class agent and an entirely new modality for treating HCV infection, many
      challenges were encountered during the discovery and development of this
      compound. The lessons learned in overcoming these obstacles offer insights and
      pave the way for the newly emerging field of HCV antiviral therapeutics. This
      paper will describe the discovery and development of a first-in-class direct
      antiviral treatment for chronic hepatitis C infection, boceprevir, marketed
      around the world as VictrelisTM.

PMID- 23859803
TI  - Conversion of cornstalk to bio-oil in hot-compressed water: effects of ultrasonic
      pretreatment on the yield and chemical composition of bio-oil, carbon balance,
      and energy recovery.
AB  - An ultrasonic pretreatment method was developed to enhance the yield of bio-oil
      obtained from the liquefaction of cornstalks in hot-compressed water at different
      reaction temperatures (260-340  degrees C) and residence times (0-40 min).
      Influences of ultrasonic pretreatment on the physicochemical properties of
      cornstalks and bio-oil yields were investigated. The results show that ultrasonic
      pretreatment obviously increases surface areas of cornstalks, decreases
      crystallinities, and erodes the structures of lignin, leading to more exposure of
      cellulose and hemicellulose. The yield of bio-oil was increased remarkably by
      10.1% for 40 min sonicated cornstalks under the optimum liquefied conditions (300
      degrees C for 0 min of residence time). Carbon balance indicates that ultrasonic
      pretreatment increases the carbon conversion of cornstalks to heavy oil and water
      soluble oil. Energy balance indicates that the sonicated cornstalks have positive
      energy efficiencies. GC-MS analyses demonstrate ultrasonic pretreatment increases
      the contents of the phenols in heavy oil and water-soluble oil. 

PMID- 23859804
TI  - Excess of O-linked N-acetylglucosamine modifies human pluripotent stem cell
      differentiation.
AB  - O-linked-N-acetylglucosamine (O-GlcNAc), a post translational modification, has
      emerged as an important cue in controlling key cell mechanisms. Here, we
      investigate O-GlcNAc's role in the maintenance and differentiation of human
      pluripotent stem cells (hPSC). We reveal that protein expression of O-GlcNAc
      transferase and hydrolase both decreases during hPSC differentiation.
      Upregulating O-GlcNAc with O-GlcNAc hydrolase inhibitors has no significant
      effect on either the maintenance of pluripotency in hPSC culture, or the loss of
      pluripotency in differentiating hPSC. However, in spontaneously differentiating
      hPSC, excess O-GlcNAc alters the expression of specific lineage markers: decrease
      of ectoderm markers (PAX6 by 53-88%, MSX1 by 26-49%) and increase of adipose
      related mesoderm markers (PPARgamma by 28-100%, C/EBPalpha by 46-135%). All other
      lineage markers tested (cardiac, visceral-endoderm, trophectoderm) remain
      minimally affected by upregulated O-GlcNAc. Interestingly, we also show that
      excess O-GlcNAc triggers a feedback mechanism that increases O-GlcNAc hydrolase
      expression by 29-91%. To the best of our knowledge, this is the first report
      demonstrating that excess O-GlcNAc does not affect hPSC pluripotency in
      undifferentiated maintenance cultures; instead, it restricts the hPSC
      differentiation towards specific cell lineages. These data will be useful for
      developing targeted differentiation protocols and aid in understanding the
      effects of O-GlcNAc on hPSC differentiation. 

PMID- 23859806
TI  - Psychosocial factors associated with male sexual difficulties.
AB  - The role of medical conditions, childhood experiences, and psychological and
      relationship factors in the development and maintenance of male sexual
      difficulties is not well understood. Using self-report questionnaires, the
      current study examined how these factors are associated with male sexual
      difficulties overall, as well as for each of four separate problems (low sexual
      desire, erectile difficulties, premature ejaculation, delayed ejaculation). The
      participants for the study were 331 Australian men from the general population,
      all of whom were in cohabiting heterosexual relationships and had experienced one
      or more of the aforementioned sexual problems. Data were collected via an online
      survey between January 2010 and April 2011. The results demonstrated that medical
      factors as well as current psychological factors (e.g., performance anxiety) were
      most likely associated with each male sexual difficulty. These findings are in
      contrast to those obtained with women, where relationship factors are strongly
      related to female sexual problems. They would suggest that the targets for sex
      therapy may be different for men and women, with medical problems and performance
      anxiety being the primary targets for men. 

PMID- 23859805
TI  - Loss of androgen receptor promotes adipogenesis but suppresses osteogenesis in
      bone marrow stromal cells.
AB  - Gender differences have been described in osteoporosis with females having a
      higher risk of osteoporosis than males. The differentiation of bone marrow
      stromal cells (BMSCs) into bone or fat is a critical step for osteoporosis. Here
      we demonstrated that loss of the androgen receptor (AR) in BMSCs suppressed
      osteogenesis but promoted adipogenesis. The mechanism dissection studies revealed
      that AR deficiency suppressed osteogenesis-related genes to inhibit osteoblast
      differentiation from BMSCs. Knockout of AR promoted adipogenesis of BMSCs via Akt
      activation through IGFBP3-mediated IGF signaling, and the 5' promoter assay and
      chromatin immunoprecipitation assays further proved that AR could modulate IGFBP3
      expression at the transcriptional level. Finally, addition of IGF inhibitors
      successfully masked the AR deficiency-induced Akt activation, and inhibitions of
      Akt, IGF1, and IGF2 pathways reversed the AR depletion effects on the
      adipogenesis process. These results suggested that AR-mediated changes in IGFBP3
      might modulate the IGF-Akt axis to regulate adipogenesis in BMSCs. 

PMID- 23859807
TI  - First do no harm: pressing concerns regarding euthanasia in Belgium.
AB  - This article is concerned with the practice of euthanasia in Belgium. Background
      information is provided; then major developments that have taken place since the
      enactment of the Belgian Act on Euthanasia are analysed. Concerns are raised
      about (1) the changing role of physicians and imposition on nurses to perform
      euthanasia; (2) the physicians' confusion and lack of understanding of the Act on
      Euthanasia; (3) inadequate consultation with an independent expert; (4) lack of
      notification of euthanasia cases, and (5) organ transplantations of euthanized
      patients. Some suggestions designed to improve the situation and prevent abuse
      are offered. 

PMID- 23859808
TI  - Diabetes mellitus and risk of cancer in Takayama: a population-based prospective
      cohort study in Japan.
AB  - Diabetes mellitus (DM) has been reported to be associated with an increased risk
      of site-specific cancers; however, few studies have assessed associations of DM
      with both total and site-specific cancers in Japan. We examined the association
      of a history of DM with cancer incidence in a population-based prospective cohort
      study in Japan. A total of 14 173 men and 16 547 women over 35 years old, who
      completed a self-administered baseline questionnaire in 1992, were followed up
      for cancer incidence from September 1992 to March 2008. At baseline, 6.3% men and
      2.9% women had a history of diabetes. A total of 1974 men and 1514 women were
      identified as newly diagnosed with cancer. Hazard ratios (HR) and 95% confidence
      intervals (CI) were determined using Cox proportional hazards models. After
      controlling for potential confounders, men with DM had a modest risk increase of
      total cancer occurrence compared with those without DM (HR, 1.09; 95% CI, 0.93
      1.29). Increased risk of cancer of the liver (HR, 2.18; 95% CI, 1.27-3.74), bile
      duct (HR, 2.17; 95% CI, 1.01-4.66), and larynx (HR, 3.61; 95% CI, 1.16-11.2) in
      diabetic men were observed. In women, significant increased risk of total cancer
      (HR, 1.35; 95% CI, 1.06-1.73) and stomach cancer (HR, 2.15; 95% CI, 1.30-3.54)
      were observed among diabetic subjects. These data suggest that people with DM may
      be at increased risk of both total and some site-specific cancers.

PMID- 23859809
TI  - Transplantation of mesenchymal stem cells into the skeletal muscle induces
      cytokine generation.
AB  - Mesenchymal stem cells due to the high proliferative potential, capacity of
      multilineage differentiation became a hope of regenerative medicine. However, the
      organism's response to the transplantation of MSCs is not fully elucidated. The
      aim of the present study was to evaluate the acute local tissue response to
      syngeneic MSCs administration into the muscle. Rat syngeneic MSCs were
      transplanted into the skeletal muscle and the tissue surrounding the injection
      site was collected after 24h. Analogous samples from untreated and PBS treated
      muscles served as controls. The analysis of genes expression using real-time PCR
      revealed significant up-regulation of proinflammatory cytokines: IL-1alpha, IL
      1beta, IL-6 in MSCs treated muscles in comparison to the PBS group. The
      evaluation of protein concentration (ELISA) in collected samples showed that
      injection of MSCs caused significant elevation of IL-1beta. Immunofluorescent
      assessment of the tissue revealed infiltration of leukocytes and macrophages.
      Quantitative analysis of the samples immunostained for CD68 and CD43 antigens
      revealed that the number of phagocytes was significantly higher in MSC treated
      muscle when compared to the samples from PBS group. To conclude, the
      administration of mesenchymal stem cells into the muscle in syngeneic model
      induces the features of acute inflammation that affects cell engraftment.

PMID- 23859811
TI  - Surface charge and interfacial potential of titanium dioxide nanoparticles:
      experimental and theoretical investigations.
AB  - Size dependent surface charging and interfacial potential of titanium dioxide
      (TiO2) nanoparticles are investigated by experimental and theoretical methods.
      Commercially available TiO2 (P25) nanoparticles were used for surface charge
      determinations by potentiometric titrations. Anatase particles, 10 and 22 nm in
      diameter, were synthesized by controlled hydrolysis of TiCl4, and electrophoretic
      mobilities were determined at a fixed pH but at increasing salt concentrations.
      Corrected Debye-Huckel theory of surface complexation (CDH-SC) was modified to
      model the size dependent surface charging behavior of TiO2 nanoparticles.
      Experimentally determined surface charge densities of rutile and P25
      nanoparticles in different electrolytes were accurately modeled by the CDH-SC
      theory. Stern layer capacitances calculated by the CDH-SC theory were in good
      agreement with the values found by the classical surface complexation approach,
      and the interaction of protons with OH groups is found to be less exothermic than
      for iron oxide surfaces. Moreover, the CDH-SC theory predicts that the surface
      charge density of TiO2 nanoparticles of diameter <10nm is considerably higher
      than for larger particles, and pH at the point of zero charge (pHPZC) shifts to
      higher pH values as the particle size decreases. The importance of including the
      particle size in calculating the zeta potentials from mobilities is demonstrated.
      Smoluchowski theory showed that 10nm particles had lower zeta potential than 22
      nm particles, whereas a reverse trend was seen when zeta potentials were
      calculated by Ohshima's theory in which particle size is included. Electrokinetic
      charge densities calculated from zeta potentials were found to be only one third
      of the true surface charge densities.

PMID- 23859810
TI  - Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential
      regulation by key cytokines implicated in atherosclerosis and novel synergism
      between TL1A and IL-17.
AB  - Atherosclerosis is an inflammatory disease of the vasculature regulated by
      cytokines. Macrophages play a crucial role at all stages of this disease,
      including regulation of foam cell formation, the inflammatory response and
      stability of atherosclerotic plaques. For example, matrix metalloproteinases
      produced by macrophages play an important role in modulating plaque stability.
      More recently, the ADAMTS proteases, which are known to play a key role in the
      control of cartilage degradation during arthritis, have been found to be
      expressed in atherosclerotic lesions and suggested to have potentially important
      functions in the control of plaque stability. Unfortunately, the action of
      cytokines on the expression of ADAMTS family in macrophages is poorly understood.
      We have investigated the effect of classical cytokines (IFN-gamma and TGF-beta)
      and those that have been recently identified (TL1A and IL-17) on the expression
      of ADAMTS-1, -4 and -5 in human macrophages. The expression of all three ADAMTS
      members was induced during differentiation of monocytes into macrophages. TGF
      beta had a differential action with induction of ADAMTS-1 and -5 expression and
      attenuation in the levels of ADAMTS-4. In contrast, IFN-gamma suppressed the
      expression of ADAMTS-1 without having an effect on ADAMTS-4 and -5. Although TL
      1A or IL-17A alone had little effect on the expression of all the members, they
      induced their expression synergistically when present together. These studies
      provide new insight into the regulation of key ADAMTS family members in human
      macrophages by major cytokines in relation to atherosclerosis.

PMID- 23859812
TI  - Towards the synthesis of hydroxyapatite/protein scaffolds with controlled
      porosities: bulk and interfacial shear rheology of a hydroxyapatite suspension
      with protein additives.
AB  - The synthesis of porous hydroxyapatite scaffolds is essential for biomedical
      applications such as bone tissue engineering and replacement. One way to induce
      macroporosity, which is needed to support bone in-growth, is to use protein
      additives as foaming agents. Another reason to use protein additives is the
      potential to introduce a specific biofunctionality to the synthesized scaffolds.
      In this work, we study the rheological properties of a hydroxyapatite suspension
      system with additions of the proteins bovine serum albumin (BSA), lysozyme (LSZ)
      and fibrinogen (FIB). Both the rheology of the bulk phase as well as the
      interfacial shear rheology are studied. The bulk rheological data provides
      important information on the setting behavior of the thixotropic suspension,
      which we find to be faster with the addition of FIB and LSZ and much slower with
      BSA. Foam bubble stabilization mechanisms can be rationalized via interfacial
      shear rheology and we show that it depends on the growth of interfacial films at
      the suspension/air interface. These interfacial films support the stabilization
      of bubbles within the ceramic matrix and thereby introduce macropores. Due to the
      weak interaction of the protein molecules with the hydroxyapatite particles of
      the suspension, we find that BSA forms the most stable interfacial films,
      followed by FIB. LSZ strongly interacts with the hydroxyapatite particles and
      thus only forms thin films with very low elastic moduli. In summary, our study
      provides fundamental rheological insights which are essential for tailoring
      hydroxyapatite/protein suspensions in order to synthesize scaffolds with
      controlled porosities. 

PMID- 23859813
TI  - Numerical study of active control of mixing in electro-osmotic flows by
      temperature difference using lattice Boltzmann methods.
AB  - In this paper, the effect of temperature difference between inlet flow and walls
      on the electro-osmotic flow through a two-dimensional microchannel is
      investigated. The main objective is to study the effect of temperature variations
      on the distribution of ions and consequently internal electric potential field,
      electric body force, and velocity fields in an electro-osmotic flow. We assume
      constant temperature and zeta potential on walls and use the mean temperature of
      each cross section to characterize the Boltzmann ion distribution across the
      channel. Based on these assumptions, the multiphysical transports are still able
      to be described by the classical Poisson-Boltzmann model. In this work, the
      Navier-Stokes equation for fluid flow, the Poisson-Boltzmann equation for ion
      distribution, and the energy equation for heat transfer are solved by a couple
      lattice Boltzmann method. The modeling results indicate that the temperature
      difference between walls and the inlet solution may lead to two symmetrical
      vortices at the entrance region of the microchannel which is appropriate for
      mixing enhancements. The advantage of this phenomenon for active control of
      mixing in electro-osmotic flow is the manageability of the vortex scale without
      extra efforts. For instance, the effective domain of this pattern could broaden
      by the following modulations: decreasing the external electric potential field,
      decreasing the electric double layer thickness, or increasing the temperature
      difference between inlet flow and walls. This work may provide a novel strategy
      for design or optimization of microsystems. 

PMID- 23859814
TI  - Design of a viscose based solid amine fiber: effect of its chemical structure on
      adsorption properties for carbon dioxide.
AB  - A solid amine fiber VF-AM-TETA was designed with viscose (VF) substrate for
      efficient CO2 capture, where its hydroxyl groups could serve synergizing effect
      in CO2-amine reaction. When grafting modification and subsequent amination were
      applied to VF, effect of structures of grafting monomers as well as amines on its
      CO2 adsorption properties was taken into account. Amines with different 1 degrees
      and 2 degrees  amine ratios were investigated as amination agents in terms of
      amine efficiency, so as to afford the fibrous adsorbent with maximum effective
      reactive amine sites for CO2 capturing. Results suggested that higher content in
      primary amine can facilitate CO2 adsorption onto the fiber by stronger basicity
      and smaller steric hindrance. Consequently, optimal chemical structure provided
      VF-AM-TETA with satisfactory adsorption capacity of 4.08 mmol/g when amine
      content was 8.74 mmol/g. Constant adsorption behavior within 6 adsorption
      desorption cycles indicated its desirable regeneration performance in practical
      use due to excellent mechanical properties of VF-AM-TETA.

PMID- 23859815
TI  - Self-suspended permanent magnetic FePt ferrofluids.
AB  - We present the synthesis and characterization of a new class of self-suspended
      ferrofluids that exhibit remanent magnetization at room temperature. Our system
      relies on the chemisorption of a thiol-terminated ionic liquid with very low
      melting point on the surface of L10 FePt nanoparticles. In contrast, all types of
      ferrofluids previously reported employ either volatile solvents as the suspending
      media or superparamagnetic iron oxide nanoparticles (that lacks permanent
      magnetization) as the inorganic component. The ferrofluids do not show any sign
      of flocculation or phase separation, despite the strong interactions between the
      magnetic nanoparticles due to the strong chemisorption of the ionic liquid as
      evidenced by Raman spectroscopy and thermal analysis. Composites with high FePt
      loading (40 and 70 wt%) exhibit a pseudo solid-like rheological behavior and high
      remanent magnetization values (10.1 and 12.8 emu/g respectively). At lower FePt
      loading (12 wt%) a liquid like behavior is observed and the remanent and
      saturation magnetization values are 3.5 and 6.2 emu/g, respectively. The magnetic
      and flow properties of the materials can be easily fine tuned by controlling the
      type and amount of FePt nanoparticles used.

PMID- 23859816
TI  - Interactions of Pluronic block copolymers with lipid monolayers studied by epi
      fluorescence microscopy and by adsorption experiments.
AB  - The interactions of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene
      oxide) (PEO-PPO-PEO) triblock copolymers, i.e. Pluronics F87, F88 and F127, with
      monolayers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were investigated with
      different monolayer techniques. Surface pressure-area isotherms were recorded of
      co-spread Pluronic/lipid mixtures with different Pluronic content to determine
      the influence of the polymers on the monolayer phase transitions. The squeeze-out
      pressure of the polymers upon film compression was dependent on the PPO block
      length. The monolayer compression experiments were coupled with fluorescence
      microscopy to visualize the phase separation into polymer-rich and lipid-rich
      domains and to monitor morphological changes of the lipid domains in the
      monolayer. Extensive phase separation was observed in the coexistence region
      between liquid-expanded (LE) and liquid-condensed (LC) lipid phases, where pure
      polymer domains coexisting with round LE-domains containing polymer, and polymer
      free LC-domains were seen. We also investigated the adsorption of Pluronics to a
      lipid monolayer after injecting a polymer solution underneath a pre-formed lipid
      monolayer by following the change in pressure at constant area. The results show
      that polymer adsorption is a superposition of two individual processes with
      different kinetics. Pluronics with a higher hydrophobicity and with a smaller
      molecular weight adsorb faster and the type and phase state of the lipid
      determines the surface pressure where no further Pluronic molecules adsorb to the
      interface. This critical surface pressure depends on the PPO block length,
      whereas the strength of the interaction with the lipids is determined by the
      relative PEO content. This indicates that also interactions between the PEO
      blocks and the lipid headgroup region are occurring. The interactions with the
      unsaturated lipid POPC in the liquid-expanded phase turn out to be stronger than
      for lipids in the liquid-condensed phase, where the polymers are excluded. 

PMID- 23859817
TI  - X-ray computed microtomography for drop shape analysis and contact angle
      measurement.
AB  - The interaction between an atomized fluid and a solid surface has a great
      importance in many fields, both in adiabatic conditions and when heat transfer is
      involved. To investigate the behavior of many drops in contact with a surface,
      the first step is to study a single one of them and in that, surface wettability
      is key parameter. Wettability analyses are usually performed by contact angle
      measurement, in most cases using the sessile drop or captive bubble techniques.
      Such techniques require optical acquisition of a side view of the drop or bubble,
      with a series of drawbacks when conventional optics are used, in particular for
      not uniform, not planar or rough base surfaces. X-ray micro-computed tomography
      is therefore used to acquire a 3D scan of a drop gently deposited on a surface,
      with the aim to reconstruct the drop surface and to perform contact angle
      measurements on true cross-sections of the drop-surface couple. Comparison with
      contact angle measurements performed on conventional images is performed. The
      results evidence that the proposed technique is very promising for surface
      characterization and to get more accurate and detailed information about
      wettability characteristics. 

PMID- 23859818
TI  - Removal of fluoride ions from drinking water and fluoride solutions by aluminum
      modified iron oxides in a column system.
AB  - The purpose of this work was to evaluate the potential of aluminum modified iron
      oxides, in a continuous flow for removal of fluoride ions from aqueous solutions
      and drinking water. The breakthrough curves obtained for fluoride ions adsorption
      from aqueous solutions and drinking water were fitted to Thomas, Bohart-Adams,
      and bed depth service time model (BDST). Adsorption capacities at the
      breakthroughs, Thomas model constant, kinetic constant and the saturation
      concentration were determined. The results show that in general, the adsorption
      efficiency decreases as the bed depth increases, and this behavior shows that the
      adsorption is controlled by the mass transport resistance. The adsorption
      capacity for fluoride ions by CP-Al is higher for fluoride aqueous solutions than
      drinking water. 

PMID- 23859819
TI  - The pharmacokinetics of methocarbamol and guaifenesin after single intravenous
      and multiple-dose oral administration of methocarbamol in the horse.
AB  - A simple LC/MSMS method has been developed and fully validated to determine
      concentrations and characterize the concentration vs. time course of
      methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous
      dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred
      horses. The plasma concentration-time profiles for MCBL after a single
      intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment
      model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (+/- 5.93)
      MUg/mL. Terminal half-life, volume of distribution at steady-state, mean
      residence time, and systemic clearance were characterized by a median (range) of
      2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68
      10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median
      (range) terminal half-life, mean transit time, mean absorption time, and apparent
      oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h,
      and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was
      characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma
      concentrations were below the limit of detection in all samples collected after
      the single intravenous dose of MCBL whereas they were detected for up to 24 h
      after the last dose of the multiple-dose oral regimen. This difference may be
      attributed to first-pass metabolism of MCBL to GGE after oral administration and
      may provide a means of differentiating the two routes of administration.

PMID- 23859820
TI  - Palladium(II)-catalyzed synthesis of 2H,3'H-spiro[benzofuran-3,2'
      naphthoquinones].
AB  - 2H,3'H-Spiro[benzofuran-3,2'-naphthoquinones], constituting a new
      spiroheterocyclic skeleton, were synthesized starting from 2-aryloxymethyl-1,4
      naphthoquinones by means of a palladium(II)-catalyzed reaction, which is a new
      spirocyclic transformation. Under optimal conditions, i.e. 10 mol % of
      palladium(II) acetate, 15 mol % of 3,5-dichloropyridine, and 5 mol % of
      trifluoroacetic acid in acetic acid at 110  degrees C, various 2H,3'H
      spiro[benzofuran-3,2'-naphthoquinones] were synthesized in yields strongly
      dependent on the substitution pattern of the aryloxy group. Unsubstituted or
      ortho-substituted 2-aryloxymethyl-1,4-quinones were found to rearrange toward the
      corresponding 2-(4-hydroxyaryl)-1,4-quinones upon treatment with trifluoroacetic
      acid. 

PMID- 23859822
TI  - The standard lateral gene transfer model is statistically consistent for
      pectinate four-taxon trees.
AB  - Evolutionary events such as incomplete lineage sorting and lateral gene transfers
      constitute major problems for inferring species trees from gene trees, as they
      can sometimes lead to gene trees which conflict with the underlying species tree.
      One particularly simple and efficient way to infer species trees from gene trees
      under such conditions is to combine three-taxon analyses for several genes using
      a majority vote approach. For incomplete lineage sorting this method is known to
      be statistically consistent; however, for lateral gene transfers it was recently
      shown that a zone of inconsistency exists for a specific four-taxon tree
      topology, and it was posed as an open question whether inconsistencies could
      exist for other four-taxon tree topologies? In this letter we analyze all
      remaining four-taxon topologies and show that no other inconsistencies exist. 

PMID- 23859821
TI  - Occurrence of selected perfluorinated alkyl acids in lunch meals served at school
      canteens in Italy and their relevance for children's intake.
AB  - Ready-to-eat servings may be more contaminated with perfluorinated alkyl acids
      (PFAAs) than the corresponding unprocessed foods due to the presence of PFAAs in
      and transfer from food contact materials (FCM) and cookware. Therefore, the
      presence of selected PFAAs in meals served weekly at lunch time in six Italian
      school canteens was assessed. Five towns were selected representing different
      areas with local water and food supply. Daily lunch menus were sampled and pooled
      to form a composite. Analyses were carried out on the weekly composite from each
      canteen. UPLC-MS/MS quantification limits were in the 6.0-12 pg g-1 range for the
      selected PFAAs (PFHxA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, branched and non-branched
      PFOS). Non-branched PFOS was quantified in four out of six composites, with
      levels ranging from 14 to 25 pg g-1, while PFOA and PFDA were determined in two
      out of six in the range 6.5-8.2 pg g-1. Theoretical estimates and analytical
      results in the same order of magnitude indicate a negligible contribution from
      food processing and serving to meal contamination. When composite analytical data
      are transposed into dietary estimates, it is shown that Italian school-age
      children have intakes in the range of 0.3-1.1 and 0.5-1.4 ng kg-1 bw day-1 for
      PFOA and PFOS respectively, well below the corresponding tolerable daily intakes
      (TDIs).

PMID- 23859823
TI  - Dysregulated glutamate uptake by astrocytes causes oligodendroglia death in
      hypoxic perventricular white matter damage.
AB  - Excess glutamate mediates damage to oligodendroglia, resulting in myelination
      disturbances characteristic of hypoxic periventricular white matter (PWM) damage.
      We sought to examine if hypoxia altered the expression of astroglial excitatory
      amino acid transporters (EAAT1, EAAT2 and EAAT3) in the PWM, and, if so, whether
      it activated astroglial N-methyl D-aspartate receptors (NMDAR) which might lead
      to apoptosis of oligodendroglia. EAAT expression in the PWM of neonatal rats was
      measured at different time points after hypoxic exposure; it was attenuated at 7
      and 14 d following hypoxia. Hypoxia prevented the uptake of glutamate by
      astroglial EAATs causing increased levels of extracellular glutamate. Excess
      glutamate augmented the expression of functional astroglial NMDAR. Following
      hypoxia, an increase in gap junction proteins between astroglia and
      oligodendroglia aided in the spreading of NMDAR-mediated excitotoxic calcium
      signals into the latter cell type triggering its apoptosis. Hence, dysregulated
      glutamate homeostasis is believed to contribute to hypoxia-induced death of
      oligodendroglia leading to neonatal PWM damage.

PMID- 23859824
TI  - C-terminal binding proteins are essential pro-survival factors that undergo
      caspase-dependent downregulation during neuronal apoptosis.
AB  - C-terminal binding proteins (CtBPs) are transcriptional co-repressors that are
      subject to proteasome-dependent downregulation during apoptosis. Alternative
      mechanisms that regulate CtBP expression are currently under investigation and
      the role of CtBPs in neuronal survival is largely unexplored. Here, we show that
      CtBPs are downregulated in cerebellar granule neurons (CGNs) induced to undergo
      apoptosis by a variety of stressors. Moreover, antisense-mediated downregulation
      of CtBP1 is sufficient to cause CGN apoptosis. Similarly, the CtBP inhibitor, 4
      methylthio-2-oxobutyric acid, induces expression of the CtBP target Noxa and
      causes actinomycin-sensitive CGN apoptosis. Unexpectedly, we found that the
      mechanism of CtBP downregulation in CGNs undergoing apoptosis varies in a
      stimulus-specific manner involving either the proteasome or caspases. In the case
      of CGNs deprived of depolarizing potassium (5K apoptotic condition), caspases
      appear to play a dominant role in CtBP downregulation. However, incubation in 5K
      does not enhance the kinetics of CtBP1 degradation and recombinant CtBP1 is not
      cleaved in vitro by caspase-3. In addition, 5K has no significant effect on CtBP
      transcript expression. Finally, mouse embryonic stem cells display caspase
      dependent downregulation of CtBP1 following exposure to staurosporine, an effect
      that is not observed in DGCR8 knockout cells which are deficient in miRNA
      processing. These data identify caspase-dependent downregulation of CtBPs as an
      alternative mechanism to the proteasome for regulation of these transcriptional
      co-repressors in neurons undergoing apoptosis. Moreover, caspases appear to
      regulate CtBP expression indirectly, at a post-transcriptional level, and via a
      mechanism that is dependent upon miRNA processing. We conclude that CtBPs are
      essential pro-survival proteins in neurons and their downregulation contributes
      significantly to neuronal apoptosis via the de-repression of pro-apoptotic genes.

PMID- 23859825
TI  - Pulsatile and steady-state hemodynamics of the human patella bone by diffuse
      optical spectroscopy.
AB  - The cardiac cycle related pulsatile behavior of the absorption and scattering
      coefficients of diffuse light and the corresponding alterations in hemoglobin
      concentrations in the human patella was studied. The pulsations in scattering is
      considerably smaller than absorption. The difference in amplitude of absorption
      coefficient pulsations for different wavelengths was translated to pulsations in
      oxygenated and deoxygenated hemoglobin, which leads to strong pulsations in the
      total hemoglobin concentration and oxygen saturation. The physiological origin of
      the observed signals was confirmed by applying a thigh-cuff. Moreover, we have
      investigated the optical and physiological properties of the patella bone and
      their changes in response to arterial cuff occlusion. 

PMID- 23859826
TI  - Social support and parenting self-efficacy among Chinese women in the perinatal
      period.
AB  - OBJECTIVE: to examine the changes in and relationship between perceived social
      support and parenting self-efficacy in the perinatal period among pregnant women
      in mainland China. DESIGN AND SETTING: this was a secondary analysis with data
      from part of an experimental study of the effects of an interpersonal
      psychotherapy-oriented childbirth psychoeducation programme on maternal
      adaptation. A longitudinal design was employed in the present study. The study
      was carried out from July 2008 to May 2009 in one general hospital in Guangzhou,
      China. PARTICIPANTS: a convenience sample of 68 first-time mothers in mainland
      China completed measurement of social support and parenting self-efficacy during
      pregnancy and at six weeks and three months post partum. FINDINGS: perceived
      social support and parenting self-efficacy declined during early motherhood.
      Parenting self-efficacy increased from six weeks post partum to three months post
      partum. Perceived social support positively correlated with parenting self
      efficacy. CONCLUSION: culturally competent health-care intervention should be
      developed during early motherhood to promote perceived social support and
      parenting self-efficacy for the new mothers.

PMID- 23859827
TI  - Determination of arsenic species in rice from Thailand and other Asian countries
      using simple extraction and HPLC-ICP-MS analysis.
AB  - Human exposure to arsenic (As) via rice consumption is of increasing concern. In
      the present study, the extraction and HPLC-ICP-MS analysis for As speciation in
      rice were investigated. A simple extraction with water and digestion with alpha
      amylase followed by the analysis using ion-paring mode HPLC separation was
      developed. The method showed good extraction efficiencies (generally >80%) and
      column efficiencies (>90%) for rice samples. The optimization of mobile phase
      showed well separated peaks of As species. The limits of quantification (LOQ) of
      As(III), As(V), MMA, and DMA that were calculated based on sample mass were 1.6,
      2.0, 2.0, and 1.6 MUg kg(-1), respectively. A total of 185 rice samples (various
      types of rice) collected from different four regions in Thailand and some other
      Asian countries were analyzed. The total As and inorganic As in rice samples were
      in the ranges of 22.51-375.39 and 13.89-232.62 MUg kg(-1), respectively. The
      estimated weekly intake of inorganic As from rice by Thai people accounted for
      13.91-29.22% of the provisional tolerable weekly intake (PTWI). 

PMID- 23859828
TI  - Information estimators for weighted observations.
AB  - The Shannon information content is a valuable numerical characteristic of
      probability distributions. The problem of estimating the information content from
      an observed dataset is very important in the fields of statistics, information
      theory, and machine learning. The contribution of the present paper is in
      proposing information estimators, and showing some of their applications. When
      the given data are associated with weights, each datum contributes differently to
      the empirical average of statistics. The proposed estimators can deal with this
      kind of weighted data. Similar to other conventional methods, the proposed
      information estimator contains a parameter to be tuned, and is computationally
      expensive. To overcome these problems, the proposed estimator is further modified
      so that it is more computationally efficient and has no tuning parameter. The
      proposed methods are also extended so as to estimate the cross-entropy, entropy,
      and Kullback-Leibler divergence. Simple numerical experiments show that the
      information estimators work properly. Then, the estimators are applied to two
      specific problems, distribution-preserving data compression, and weight
      optimization for ensemble regression. 

PMID- 23859829
TI  - Acne cosmetica revisited: a case-control study shows a dose-dependent inverse
      association between overall cosmetic use and post-adolescent acne.
AB  - BACKGROUND: Case-control studies to support the concept of acne cosmetica are
      lacking. OBJECTIVE: To examine the association of post-adolescent acne with the
      use of cosmetics and cosmetic procedures. METHODS: 910 post-adolescent patients
      with acne and an equal number of matched controls were studied for exposure to
      cosmetics and cosmetic procedures. A cumulative cosmetic exposure index was
      stratified into four quarters of increasing exposure. RESULTS: Comparison of
      different cumulative exposure categories with the lowest exposure category
      (multivariate analysis, logistic regression) showed that the odds ratios, which
      were always <1, progressively declined as cosmetic exposure increased [odds
      ratios (95% confidence intervals): 0.679 (0.501-0.922), 0.355 (0.258-0.487),
      0.307 (0.217-0.433)]. However, some individual cosmetics had odds ratios >1.
      CONCLUSION: Overall cosmetic use was negatively associated with post-adolescent
      acne. The term 'acne cosmetica' is appropriate in the sense that some cosmetics
      may cause acne.

PMID- 23859830
TI  - A family of hydroxypyrone ligands designed and synthesized as iron chelators.
AB  - The use of chelating agents for iron and aluminum in different clinical
      applications has found increasing attention in the last thirty years. Desferal,
      deferiprone and deferasirox, chelating agents nowadays in use, are based on
      hydroxamic groups, hydroxyl-substituted pyridinones or aromatic ring systems.
      With the aim of designing new chelators, we synthesized a series of kojic acid
      derivatives composed by two kojic units joined by linkers variously substituted.
      The huge advantages of these molecules are that they are easy and cheap to
      produce. Preliminary works on complex formation equilibria of the first group of
      ligands with iron and aluminium highlighted extremely good pMe values and gave
      evidence of the ability to scavenge iron from inside cells. On these bases a
      second set of bis-kojic ligands, whose linkers between the kojic chelating
      moieties are differentiated both in terms of type and size, has been designed,
      synthesized and characterized. The structural characterization of these new
      ligands is presented, and the protonation and iron(III) complex formation
      equilibria studied by potentiometry, UV-Visible spectrophotometry, electrospray
      ionization mass (ESI-MS) and (1)H NMR spectroscopy will be described and
      discussed. 

PMID- 23859831
TI  - Does existing research inform policies authorizing abortion for mental health
      reasons?

PMID- 23859833
TI  - A social cognitive perspective on 'understanding' and 'explaining'.
AB  - One essential methodological dichotomy introduced by Karl Jaspers into the field
      of psychopathology is the difference between 'understanding' ('Verstehen') and
      'explaining' ('Erklaren'). Jaspers emphasizes a critical epistemological divide
      between both methods: whereas 'explaining' relates to the attempt to consider
      mental disorders as consequences of impersonal natural laws, 'understanding'
      refers to the empathic appreciation of conflicts, hopes, and desires of an
      individual person. This distinction is related to the difference between
      'persons' and 'things' according to Fritz Heider, founder of the so-called
      'attribution theory' in social psychology that deals with our ability to ascribe
      mental states to others. Whereas the behavior of persons is based on
      psychological rules that are inherently characterized by ambiguity and
      uncertainty and are thus only partly predictable, the behavior of things is based
      on natural laws and is therefore fully predictable. This suggests a close
      resemblance of both accounts where 'understanding' is related to the domain of
      persons and 'explaining' is related to the domain of things or physical objects.
      Recently, understanding others has also become a central topic of modern
      cognitive neuroscience, constituting 'social neuroscience' targeted at explaining
      our human capacity of ascribing mental states to others. This shows that this
      distinction introduced by Jaspers still is an important and fundamental
      differentiation for various research fields dealing with communication and
      interaction between persons.

PMID- 23859834
TI  - A pluralist challenge to "integrative medicine": Feyerabend and Popper on the
      cognitive value of alternative medicine.
AB  - This paper is a critique of 'integrative medicine' as an ideal of medical
      progress on the grounds that it fails to realise the cognitive value of
      alternative medicine. After a brief account of the cognitive value of alternative
      medicine, I outline the form of 'integrative medicine' defended by the late
      Stephen Straus, former director of the US National Centre for Complementary and
      Alternative Medicine. Straus' account is then considered in the light of Zuzana
      Parusnikova's recent criticism of 'integrative medicine' and her distinction
      between 'cognitive' and 'opportunistic' engagement with alternative medicine.
      Parusnikova warns that the medical establishment is guilty of 'dogmatism' and
      proposes that one can usefully invoke Karl Popper's 'critical rationalism' as an
      antidote. Using the example of Straus, I argue that an appeal to Popper is
      insufficient, on the grounds that 'integrative medicine' can class as a form of
      cognitively-productive, critical engagement. I suggest that Parusnikova's appeal
      to Popper should be augmented with Paul Feyerabend's emphasis upon the role of
      'radical alternatives' in maximising criticism. 'Integrative medicine' fails to
      maximise criticism because it 'translates' alternative medicine into the theories
      and terminology of allopathic medicine and so erodes its capacity to provide
      cognitively-valuable 'radical alternatives'. These claims are then illustrated
      with a discussion of 'traditional' and 'medical' acupuncture. I conclude that
      'integrative medicine' fails to exploit the cognitive value of alternative
      medicine and so should be rejected as an ideal of medical progress. 

PMID- 23859832
TI  - Modeling anesthetic developmental neurotoxicity using human stem cells.
AB  - Mounting preclinical evidence in rodents and nonhuman primates has demonstrated
      that prolonged exposure of developing animals to general anesthetics can induce
      widespread neuronal cell death followed by long-term memory and learning
      disabilities. In vitro experimental evidence from cultured neonatal animal
      neurons confirmed the in vivo findings. However, there is no direct clinical
      evidence of the detrimental effects of anesthetics in human fetuses, infants, or
      children. Development of an in vitro neurogenesis system using human stem cells
      has opened up avenues of research for advancing our understanding of human brain
      development and the issues relevant to anesthetic-induced developmental toxicity
      in human neuronal lineages. Recent studies from our group, as well as other
      groups, showed that isoflurane influences human neural stem cell proliferation
      and neurogenesis, whereas ketamine induces neuroapoptosis. Application of this
      high throughput in vitro stem cell neurogenesis approach is a major stride toward
      ensuring the safety of anesthetic agents in young children. This in vitro human
      model allows us to (1) screen the toxic effects of various anesthetics under
      controlled conditions during intense neuronal growth, (2) find the trigger for
      the anesthetic-induced catastrophic chain of toxic events, and (3) develop
      prevention strategies to avoid this toxic effect. In this article, we reviewed
      the current findings in anesthetic-induced neurotoxicity studies, specifically
      focusing on the in vitro human stem cell model. 

PMID- 23859835
TI  - A novel multi-commutated method for the determination of hydroxytyrosol in
      enriched foods using mercaptopropionic acid-capped CdTe quantum dots.
AB  - Hydroxytyrosol (HXT) has been reported to have beneficial effects for human
      health, such as antioxidant and antimicrobial properties and an important
      contribution to the prevention of cardiovascular disease. Hence, exhaustive
      research is currently being performed to prepare functional foods, such as tomato
      juice or milk, with HXT. This paper presents a multi-commutated flow method based
      on the quenching effect that HXT has on the fluorescence of water-soluble
      mercaptopropionic acid-capped CdTe quantum dots. Under optimal conditions a
      linear working range was obtained for concentrations between 10 and 250 ng ul-1.
      In order to demonstrate the suitability of the proposed method for the
      determination of HXT, HXT-enriched samples were prepared. Using a QuEChERS
      (quick, easy, cheap, effective, rugged and safe) procedure for extraction, HXT
      was determined in the prepared functional foods (milk, infant formula, tomato
      juice and tomato soup). Recoveries of 100% +/- 8%, relative standard deviations
      (RSDs) lower than 5% and high sample throughput of 70 samples per h show the
      potential of the system for the analysis of HXT in food samples.

PMID- 23859836
TI  - Spot signs in intracerebral hemorrhage: useful for identifying patients at risk
      for hematoma enlargement?
AB  - BACKGROUND: Prognostic signs for the identification of patients with acute
      spontaneous intracerebral hemorrhage (SICH) prone to hematoma expansion are
      limited. Contrast extravasation (spot signs, SpS) on computed tomographic
      angiography (CTA) may be a promising method to predict hematoma expansion in
      acute SICH. However, prospective data on the predictive value of the SpS on
      hematoma expansion and clinical outcome are still limited. We aimed to
      investigate associations between the presence of SpS, hematoma expansion, and
      clinical outcome in acute SICH. METHODS: A prospective observational study was
      performed between 08/2008 and 08/2011. Patients with SICH presenting within 6 h
      of symptom onset were included. Patients with secondary hematomas, purely
      intraventricular hematomas, incomplete CT evaluation, hematoma evacuation prior
      to follow-up brain imaging, and incomplete follow-up data and those who refused
      to give consent for data analysis were excluded. CT and CTA brain imaging were
      carried out in all patients at baseline. After 24 h, follow-up brain imaging was
      performed. Hematoma location, hematoma volume, and substantial hematoma expansion
      were documented. CTA images were evaluated by two investigators for the presence
      of SpS. In all positive SpS cases, images were additionally reviewed by a third
      rater to achieve consensus for interpretating contrast extravasation. Clinical
      outcome was measured by the modified Rankin Scale (mRS) at discharge and at 3
      months. RESULTS: In total, 101 patients [median age 73 years (interquartile range
      60-79); male 61.4%] were included in the analysis. Median time from onset to CTA
      was 128 min (interquartile range 90-209 min); median initial National Institute
      of Health Stroke Scale score was 16 (8-21). SpS were detected in 27 patients
      (26.7%). Cohen's kappa for the presence of SpS was 0.606, indicating moderate
      agreement. SpS patients had significantly higher initial hematoma volumes than
      patients without SpS (36.0 vs. 14.39 ml, p = 0.005). Hematoma expansion was
      significantly more frequent in SpS patients (59.3 vs. 21.6%, p < 0.001) and
      associated with the presence of SpS in the univariate analysis (OR 5.273; 95% CI
      2.047-13.584, p = 0.001) and in multivariable analysis adjusted for the initial
      hematoma volume (OR 4.678, 95% CI 1.781-12.288, p = 0.002). Sensitivity of SpS to
      predict hematoma expansion was 0.5, specificity was 0.84. The positive likelihood
      ratio for SpS to predict hematoma expansion was 3.136 (95% CI 1.649-5.967), the
      negative likelihood ratio was 0.595 (95% CI 0.414-0.854). No difference in 3
      month clinical outcome was observed between patients with and without SpS (median
      mRS score 4 and 4, p = 0.457). CONCLUSIONS: The clinical value of SpS needs to be
      further explored. Future studies should particularly focus on structured training
      procedures to identify SpS and measure the time needed to precisely assess the
      presence of SpS and on the prevalence of SpS in consecutive intracerebral
      hemorrhage populations.

PMID- 23859837
TI  - Novel structural labeling method using cryo-electron tomography and biotin
      streptavidin system.
AB  - There are a number of large macromolecular complexes that play important roles in
      the cell, and identifying the positions of their components is a key step to
      understanding their structure and function. Several structural labeling methods
      have been applied to electron microscopy in order to locate a specific component
      within a macromolecular complex, but each method is associated with problems in
      specificity, occupancy, signal intensity or precision. Here, we report a novel
      method for identifying the 3D locations of proteins using biotin-streptavidin
      labeling and cryo-electron tomography. We labeled a biotinylation-tagged
      intermediate chain of an axonemal dynein by streptavidin within the Chlamydomonas
      axoneme and visualized the 3D positions of the labels using subtomogram
      averaging. Increase of the density attributed to the bound streptavidin was
      validated by Student's t-test. In conclusion, the combination of the biotin
      streptavidin system and cryo-electron tomography is a powerful method to
      investigate the structure of large macromolecular complexes. 

PMID- 23859838
TI  - Folic acid attenuates hyperhomocysteinemia-induced glomerular damage in rats.
AB  - The present study investigated whether lowering plasma homocysteine (Hcy) with
      folic acid (FA) could attenuate hyperhomocysteinemia (HHcy)-associated glomerular
      damage and possible mechanisms. The HHcy animal model was established by
      intragastric administration with l-methionine in rats. FA was also given
      intragastrically. Plasma Hcy and creatinine and urinary albumin were measured.
      Histological and ultrastructural changes were observed by light and electron
      microscopes. The expression of alpha-smooth muscle actin (alpha-SMA),
      proliferating cell nuclear antigen (PCNA) and transforming growth factor-beta1
      (TGF-beta1) in the kidney was examined by immunohistochemical staining and
      western blot analysis. The administration of l-methionine induced HHcy in rats.
      The HHcy rats developed glomerulosclerosis and fibrosis. Plasma creatinine
      concentration and urinary albumin excretion were also significantly increased in
      HHcy rats. Effacement and extensively fusion of podocyte foot process was
      observed in HHcy rats, which was associated with decreased expression of nephrin
      protein in renal cortex of HHcy rats. Supplementation with FA lowered plasma Hcy
      significantly. Plasma creatinine concentration and urinary albumin excretion were
      also significantly attenuated by FA. Morphologically, HHcy-associated
      glomerulosclerosis, fibrosis, podocyte foot process effacement and loss of
      podocyte nephrin, were significantly improved by FA. The expressions of alpha
      SMA, PCNA and TGF-beta1 were increased in renal cortex of HHcy rats, and which
      were also partially reversed by FA. These data suggest that elevated plasma Hcy
      is an important pathogenic factor for glomerular damage. Lowering plasma Hcy by
      FA can inhibit TGF-beta1 expression and attenuate HHcy-induced glomerular damage.

PMID- 23859839
TI  - A systematic review of interventions for reducing parental vaccine refusal and
      vaccine hesitancy.
AB  - Unvaccinated individuals pose a public health threat to communities. Research has
      identified many factors associated with parental vaccine refusal and hesitancy
      toward childhood and adolescent immunizations. However, data on the effectiveness
      of interventions to address parental refusal are limited. We conducted a
      systematic review of four online databases to identify interventional studies. We
      used criteria recommended by the WHO's Strategic Advisory Group of Experts on
      immunization (SAGE) for the quality assessment of studies. Intervention
      categories and outcomes were evaluated for each body of evidence and confidence
      in overall estimates of effect was determined. There is limited evidence to guide
      implementation of effective strategies to deal with the emerging threat of
      parental vaccine refusal. There is a need for appropriately designed, executed
      and evaluated intervention studies to address this gap in knowledge. 

PMID- 23859840
TI  - Behavioral risk assessment in HIV Vaccine Trials Network (HVTN) clinical trials:
      a qualitative study exploring HVTN staff perspectives.
AB  - In HIV vaccine trials, the collection and analysis of participant behavior data
      associated with risk of acquiring HIV-infection is important for a number of
      reasons. Although the rationale for behavioral risk assessment in HIV vaccine
      clinical trials is clear, consistent collection of behavioral data over time and
      across protocols has been challenging for the HIV Vaccine Trials Network (HVTN).
      Integrating biomedical and behavioral research within the same preventive vaccine
      clinical trial has proven difficult. The HVTN conducted an internal landscape
      analysis to: (1) evaluate the challenges of behavioral risk assessment in HIV
      vaccine trials and observational studies; (2) explore the impact of the Step
      Study on behavioral risk assessment measures; and (3) identify strategies to
      overcome existing challenges and improve the quality of data resulting from
      behavioral risk analysis. These analyses of behavioral risk within the HVTN
      revealed several challenges and recommendations for improved behavioral risk data
      collection in future protocols. The recommendations for improvement include: (1)
      establishment of protocol-specific behavioral risk working groups that include
      social and behavioral experts; (2) provision of behavioral rationale and
      objectives to the development team; (3) creation of a template for geographic-
      and population-specific assessment of low and high risk behaviors; and (4) pilot
      testing of behavioral risk assessments. Results also underscored the need for
      routinely conducted analyses of behavioral data. 

PMID- 23859841
TI  - Delivery of synthetic RNA can enhance the immunogenicity of vaccines against foot
      and-mouth disease virus (FMDV) in mice.
AB  - We have recently described the antiviral effect in mice of in vitro-transcribed
      RNAs mimicking structural domains in the non-coding regions of the foot-and-mouth
      disease virus (FMDV) genome RNA. These small, synthetic and non-infectious RNA
      molecules (ncRNAs) are potent type-I interferon (IFN) inducers in vivo. In this
      work, the immunomodulatory effect of the ncRNA corresponding to the internal
      ribosome entry site (IRES) on immunization with two different FMD vaccine
      formulations, both based on inactivated virus, including or not a commercial
      adjuvant, was analyzed in the mice model. The effect of the time interval between
      RNA inoculation and immunization was also studied. RNA delivery consistently
      increased the titers of specific anti-FMDV antibodies, including neutralizing
      antibodies, elicited after vaccination. Moreover, at day 2 after immunization,
      significant differences in mean antibody titers could be detected between the
      groups of mice receiving either vaccine co-administered with the RNA and the
      control group, unlike those immunized with the vaccine alone. When vaccinated
      mice were challenged with FMDV, the mean values of viral load were lower in the
      groups receiving the RNA together with the vaccine. Our results show the
      enhancing effect of the IRES RNA on the immune response elicited after
      vaccination and suggest the potential of this molecule as an adjuvant for new FMD
      vaccine design. 

PMID- 23859842
TI  - Seroepidemiology of diphtheria and tetanus among children and young adults in
      Tajikistan: nationwide population-based survey, 2010.
AB  - BACKGROUND: Tajikistan had a major diphtheria outbreak (~ 10,000 cases) in the
      1990 s, which was controlled after nationwide immunization campaigns with
      diphtheria-tetanus toxoid in 1995 and 1996. Since 2000, only 52 diphtheria cases
      have been reported. However, in coverage surveys conducted in 2000 and 2005,
      diphtheria-tetanus-pertussis vaccine coverage was lower than administratively
      reported estimates raising concerns about potential immunity gaps. To further
      assess population immunity to diphtheria in Tajikistan, diphtheria antibody
      testing was included in a large-scale nationwide serosurvey for vaccine
      preventable diseases conducted in connection with a poliomyelitis outbreak in
      2010. In addition, the serosurvey provided an opportunity to assess population
      immunity to tetanus. METHODS: Residents of all regions of Tajikistan aged 1-24
      years were included in the serosurvey implemented during September-October 2010.
      Participants were selected through stratified cluster sampling. Specimens were
      tested for diphtheria antibodies using a Vero cell neutralization assay and for
      tetanus antibodies using an anti-tetanus IgG ELISA. Antibody concentrations >=
      0.1 IU/mL were considered seropositive. RESULTS: Overall, 51.4% (95% CI, 47.1%
      55.6%) of participants were seropositive for diphtheria and 78.9% (95% CI, 74.7%
      82.5%) were seropositive for tetanus. The lowest percentages of seropositivity
      for both diseases were observed among persons aged 10-19 years: diphtheria
      seropositivity was 37.1% (95% CI, 31.0%-43.7%) among 10-14 year-olds, and 35.3%
      (95% CI, 29.9%-41.1%) among 15-19 year-olds; tetanus seropositivity in respective
      age groups was 65.3% (95% CI, 58.4%-71.6%) and 70.1% (95% CI, 64.5%-75.2%).
      CONCLUSIONS: Population immunity for diphtheria in Tajikistan is low,
      particularly among 10-19 year-olds. Population immunity to tetanus is generally
      higher than for diphtheria, but is suboptimal among 10-19 year-olds. These
      findings highlight the need to improve routine immunization service delivery, and
      support a one-time supplementary immunization campaign with diphtheria-tetanus
      toxoid among birth cohorts aged 1-19 years in 2010 (3-21 years in 2012) to close
      immunity gaps and prevent diphtheria outbreaks.

PMID- 23859843
TI  - Uptake and effectiveness of monovalent influenza A (H1N1) pandemic 2009 vaccine
      among healthcare personnel in Kenya, 2010.
AB  - INTRODUCTION: During April-June 2010, the Kenya Ministry of Public Health and
      Sanitation distributed free monovalent influenza A(H1N1)pdm09 vaccines to health
      care personnel (HCP) and other vulnerable groups. We conducted a prospective,
      cohort study among HCP to characterize influenza A(H1N1)pdm09 vaccine uptake, and
      to assess influenza A(H1N1)pdm09 vaccine effectiveness. METHODS: We enrolled HCP
      from 5 hospitals and followed them for 6 months. At enrollment, we asked HCP if
      they had received the influenza A(H1N1)pdm09 vaccine and their reasons for their
      decision. We administered weekly questionnaires to participants about respiratory
      symptoms suffered during the previous week. Participants who had acute
      respiratory illness were asked to contact our surveillance clinician, and
      nasopharyngeal and oropharyngeal specimens were collected and later tested for
      influenza by real-time reverse-transcriptase polymerase-chain-reaction. Vaccine
      effectiveness was estimated by comparing the incidence of acute respiratory
      illness, absenteeism from work due to respiratory illness and laboratory
      confirmed influenza among vaccinated and unvaccinated HCP. RESULTS: We enrolled
      3803 HCP from the five hospitals; 64% received influenza vaccine. Vaccinated HCP
      were more likely to develop acute respiratory illness (ARI) and more likely to
      report missed days of work due to respiratory illness compared to non-vaccinated
      HCP (adjusted incidence rate ratio (aIRR) 1.50, 95% confidence intervals (CI):
      1.33-1.70) and (aIRR 2.02, 95% CI: 1.41-2.88), respectively. Of 531 samples
      collected from vaccinated and non-vaccinated HCP, 30 were influenza A and 3 were
      influenza B. Two influenza A(H1N1)pdm09 subtypes were isolated; one from
      vaccinated and the other from non-vaccinated HCP. DISCUSSION AND CONCLUSIONS: A
      majority of Kenyan HCP surveyed reported receiving the influenza A(H1N1)pdm09
      vaccine. Because of low circulation of influenza A(H1N1)pdm09 virus during the
      study period, vaccine effectiveness could not be determined. The findings of
      increased ARI events and missed days of work among vaccinated HCP were likely
      confounded by vaccine-seeking behavioral factors.

PMID- 23859844
TI  - Intra-arterial chemotherapy is not superior to intravenous chemotherapy for
      malignant gliomas: a systematic review and meta-analysis.
AB  - The efficacy and safety of intra-arterial (IA) chemotherapy versus intravenous
      (IV) chemotherapy for malignant gliomas were studied. We searched eight
      electronic databases to identify relevant randomized controlled trials that
      compared IA chemotherapy with IV chemotherapy in patients with malignant gliomas.
      This study was conducted in compliance with the Quality of Reporting of Meta
      analysis (QUORUM) guidelines. The quality of data was assessed using the Grades
      of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. Four
      eligible randomized controlled trials including 460 patients were retrieved.
      Comparing IA chemotherapy and IV chemotherapy for malignant gliomas, disease
      control rate, efficacy rate, 1-year, 2-year, and 3-year overall survival as well
      as grade 3/4 leukocytopenia, thrombocytopenia, and anemia were not statistically
      different. In conclusion, IA chemotherapy is not superior to IV chemotherapy in
      terms of efficacy and overall survival as a treatment for malignant gliomas. 

PMID- 23859845
TI  - Influence of age, sex and breeding status on mercury accumulation patterns in the
      wandering albatross Diomedea exulans.
AB  - Although mercury bio-amplifies through the food chain and accumulates in top
      predators, mercury concentrations in tissues of the wandering albatross are
      greater than in any other vertebrate, including closely related species. In order
      to explore the alternative explanations for this pattern, we measured total
      mercury concentrations in feathers, plasma and blood cells of wandering
      albatrosses of known age, sex and breeding status sampled at South Georgia.
      Mercury concentrations were low in feathers and blood components of chicks, and
      higher in the feathers of young pre-breeders than in feathers or blood of older
      pre-breeders and breeding adults. There was no effect of sex on mercury
      concentrations in the feathers of pre-breeders or breeding adults, whereas levels
      were significantly higher in blood cells of breeding females than males. The high
      feather mercury concentrations of young pre-breeders compared with older birds
      suggest an increase in moult frequency as birds approach maturity.

PMID- 23859846
TI  - Degradation of multiwall carbon nanotubes by bacteria.
AB  - Understanding the environmental transformation of multiwall carbon nanotubes
      (MWCNTs) is important to their life cycle assessment and potential environmental
      impacts. We report that a bacterial community is capable of degrading (14)C
      labeled MWCNTs into (14)CO2 in the presence of an external carbon source via co
      metabolism. Multiple intermediate products were detected, and genotypic
      characterization revealed three possible microbial degraders: Burkholderia
      kururiensis, Delftia acidovorans, and Stenotrophomonas maltophilia. This result
      suggests that microbe/MWCNTs interaction may impact the long-term fate of MWCNTs.

PMID- 23859847
TI  - Activatable oligomerizable imaging agents for photoacoustic imaging of furin-like
      activity in living subjects.
AB  - Photoacoustic (PA) imaging is continuing to be applied for physiological imaging
      and more recently for molecular imaging of living subjects. Owing to its high
      spatial resolution in deep tissues, PA imaging holds great potential for
      biomedical applications and molecular diagnostics. There is however a lack of
      probes for targeted PA imaging, especially in the area of enzyme-activatable
      probes. Here we introduce a molecular probe, which upon proteolytic processing is
      retained at the site of enzyme activity and provides PA contrast. The probe
      oligomerizes via a condensation reaction and accumulates in cells and tumors that
      express the protease. We demonstrate that this probe reports furin and furin-like
      activity in cells and tumor models by generating a significantly higher PA signal
      relative to furin-deficient and nontarget controls. This probe could report
      enzyme activity in living subjects at depths significantly greater than
      fluorescence imaging probes and has potential for molecular imaging in deep
      tumors. 

PMID- 23859848
TI  - Validation of a spectroscopic sensor for the continuous, noninvasive measurement
      of muscle oxygen saturation and pH.
AB  - New patient monitoring technologies can noninvasively and directly provide an
      assessment of the adequacy of tissue perfusion through the simultaneous
      determination of muscle oxygen saturation (SmO2) and muscle pH (pHm). Non
      pulsatile near infrared spectroscopy is used to determine these microvascular
      parameters. Two separate studies were conducted using an isolated perfused swine
      limb preparation to widely vary venous blood oxygen saturation (SviO2) and pH
      (pHvi) to assess the accuracy of a noninvasive sensor with the capability to
      simultaneously measure both parameters. The isolated limb model is necessary to
      establish equilibrium between the venous output of the perfusion circuit and the
      venule measurement of the spectroscopic sensor. The average absolute difference
      between SmO2 and SviO2 determined over 50 conditions of SviO2 between 13% and 83%
      on 3 pig limbs was 3.8% and the coefficient of determination (R(2)) was 0.95. The
      average absolute difference between pHm and pHvi determined over 69 conditions of
      pHvi between pHvi 6.9 and pHvi 7.5 on 3 pig limbs was 0.045 pH units with an R(2)
      of 0.92. Measured accuracy was acceptable to support clinically relevant decision
      making for the assessment of impaired tissue perfusion and acidosis. Sensors were
      also evaluated on human subjects. There was no statistical difference in SmO2 by
      gender or location when multiple sensors were evaluated on the right and left
      calf, deltoid, and thigh of resting men and women (N = 33). SmO2 precision for
      subjects at rest was 5.6% over the six locations with four different sensors. 

PMID- 23859849
TI  - Cost-effectiveness analysis of MMR immunization in health care workers.
AB  - BACKGROUND: Assessment of measles, mumps and rubella (MMR) status is an essential
      part of occupational health clearance for new health care workers (HCWs). At the
      time of this study the policy at Sheffield Occupational Health Service (SOHS) was
      to perform serological testing of HCWs without evidence of previous immunization
      prior to MMR vaccination. AIMS: To identify the cost implications of changing
      policy to offer vaccination without prior serological testing to HCWs without
      evidence of previous immunization. METHODS: A retrospective cohort analysis of
      all MMR serological results from individuals attending SOHS for pre-placement
      assessment between 1 April 2010 and 31 March 2012. RESULTS: Seven thousand five
      hundred and sixty-nine individuals attended SOHS for pre-placement screening. Of
      these, 52% (3921) had no evidence of prior vaccination to at least one MMR
      disease and underwent serological testing. Thirty-three per cent (1204) of these
      HCWs were sero-negative to at least one condition requiring vaccination. With the
      suggested change in policy, our data indicate a cost-saving of over L105 000 per
      year may currently be achieved at SOHS. CONCLUSIONS: Our findings highlight
      significant savings through offering vaccination without prior serology for HCWs
      with no evidence of prior immunization to MMR. An awareness of costs associated
      with serology, vaccination and staff clinics, as well as the wider impact of
      population vaccination campaigns, are important factors determining the most cost
      effective strategy in this area.

PMID- 23859850
TI  - Prevalence of upper limb disorders among female librarians.
AB  - BACKGROUND: Work as a librarian involves exposure to potential risk factors for
      developing upper limb disorders. The prevalence of upper limb symptoms has,
      however, not previously been assessed in this occupational group. AIMS: To
      estimate the 7-day and annual prevalence of self-reported neck and upper limb
      symptoms in librarians and to examine associations with specific tasks and
      ergonomic risk factors. METHODS: A cross-sectional study using components of the
      standardized Nordic questionnaire. The study population consisted of librarians
      employed by a large local authority, and data collection was by means of a self
      administered questionnaire. RESULTS: from studies on keyboard workers and on the
      general population were used as comparators. RESULTS: The 7-day prevalence of
      self-reported neck and upper limb pain in female librarians was 42% (95%
      confidence interval (CI) 33.7-50.5) and the annual prevalence was 65% (95% CI
      56.6-72.8). The prevalence of reported wrist and hand pain increased with
      increased working involving a wide thumb-index span (P < 0.05) with a significant
      linear trend in prevalence with increasing exposure (P < 0.01). There was a
      strong association between reporting hand and/or wrist pain and awareness of work
      related upper limb disorder (P < 0.05). CONCLUSIONS: The annual prevalence of
      self-reported upper limb symptoms among female librarians was high, but there was
      insufficient evidence to confirm whether the prevalence was higher than in the
      general population or among keyboard workers. Working with a wide thumb-index
      span was associated with reporting upper limb symptoms.

PMID- 23859851
TI  - A new look for Pediatric Neurology.

PMID- 23859852
TI  - Focal cortical dysplasia.
AB  - Focal cortical dysplasias are among the most common causes of intractable
      epilepsy in children. As the neuropathology of these conditions has been better
      clarified, the nomenclature has undergone numerous revisions. Their recognition
      has grown with the use of neuroimaging, and recent advances in imaging technology
      will further improve detection. Clinical, electroencephalographic, and imaging
      findings are often diagnostic, so it is imperative for the clinician to recognize
      the characteristic patterns. Treatment for developmental and behavioral
      disability remains largely symptomatic, and epilepsy medications are often
      ineffective. Epilepsy surgery, however, can be successful in selected patients.
      The basic science underlying the development of focal cortical dysplasias may
      lead to novel therapeutic approaches in the future. 

PMID- 23859853
TI  - Antecedents of perinatal cerebral white matter damage with and without
      intraventricular hemorrhage in very preterm newborns.
AB  - BACKGROUND: Isolated periventricular leukomalacia, defined as periventricular
      leukomalacia unaccompanied by intraventricular hemorrhage, is reportedly
      increased in newborns with systemic hypotension and in infants who received
      treatment for systemic hypotension or a patent ductus arteriosus. METHODS: This
      study sought to determine if the risk profile of one or more hypoechoic lesions
      unaccompanied by intraventricular hemorrhage, our surrogate for isolated
      periventricular leukomalacia, differs from that of one or more hypoechoic lesions
      preceded or accompanied by intraventricular hemorrhage. We compared extremely
      preterm infants (i.e., gestation 23-27 weeks) with each of these entities to 885
      extremely preterm infants who had neither an isolated hypoechoic lesion nor a
      hypoechoic lesion preceded or accompanied by intraventricular hemorrhage.
      RESULTS: The risk of a hypoechoic lesion with intraventricular hemorrhage (N =
      61) was associated with gestation <25 weeks, high Score for Acute Neonatal
      Physiology, early recurrent or prolonged acidemia, analgesic exposure, and
      mechanical ventilation 1 week after birth. CONCLUSIONS: In this large,
      multicenter sample of extremely low gestational age newborns, the risk profile of
      a hypoechoic lesion unaccompanied by intraventricular hemorrhage differed from
      that of a hypoechoic lesion with intraventricular hemorrhage. This suggests that
      hypoechoic lesions accompanied or preceded by intraventricular hemorrhage (our
      surrogate for periventricular hemorrhagic infarction) may have a different causal
      pathway than hypoechoic lesions without intraventricular hemorrhage, our
      surrogate for periventricular leukomalacia.

PMID- 23859854
TI  - Neurological and muscular manifestations associated with influenza B infection in
      children.
AB  - BACKGROUND: Influenza viruses have been associated with various neurological and
      muscular symptoms. The aim of this study was to evaluate the pediatric
      neurological and muscular manifestations of influenza B during a 5-month epidemic
      at a single center. METHODS: We retrospectively reviewed the medical records of
      355 pediatric patients with laboratory-confirmed influenza B infection. RESULTS:
      Neurological and muscular symptoms were exhibited by 28 patients (7.9%). The mean
      age was 48.7 +/- 25.2 months. The mean time between respiratory symptoms and
      neurological symptoms was 2.2 +/- 1.5 days. The most common symptom was seizure
      (19/28, 67.9%), followed by myositis (5/28, 17.9%), increased intracerebral
      pressure (1/28, 3.6%), delirium (1/28, 3.6%), and severe headache (1/28, 3.6%).
      There was one severe case of meningitis with myocarditis (1/28, 3.6%). All
      seizures were febrile: 15 simple febrile seizures (78.9%), three complex febrile
      seizures (15.8%), and one febrile status epilepticus (5.3%). The mean age of nine
      patients with their first seizures was 37.9 +/- 22.2 months, which was older than
      the typical age of onset for febrile seizure. All the patients, except one, were
      treated with oseltamivir. There were no deaths or chronic debilitating sequelae.
      CONCLUSIONS: The neurological and muscular complications of influenza B infection
      in children are relatively mild, and febrile seizure is the most common. However,
      clinicians should be alert to the possibility of rare severe complications during
      influenza B outbreaks.

PMID- 23859855
TI  - Amplitude electroencephalogram characterization in preterm infants undergoing
      patent ductus arteriosus ligation.
AB  - BACKGROUND: Recent studies suggest an increased risk of neurodevelopmental
      impairment following patent ductus arteriosus surgical ligation. The mechanisms
      are unclear, but intraoperative stress or pain may contribute. The objectives of
      this study were to determine if pain, evidenced by an increase in heart rate and
      blood pressure, during patent ductus arteriosus ligation would be accompanied by
      an increase in amplitude-integrated electroencephalogram (aEEG) voltage. METHODS:
      This was an observational, pilot study of infants born at 22.6-35.1 weeks with
      patent ductus arteriosus requiring surgical ligation. The aEEG was recorded prior
      to, during surgery, and for 2 hours following surgery. Mean heart rate, blood
      pressure, and aEEG voltage were analyzed for each recording period. RESULTS:
      Seventeen preterm infants were studied at a mean postmenstrual age of 26.6 weeks.
      Following anesthetic induction, aEEG became suppressed and remained suppressed
      during the postoperative period. Heart rate and blood pressure increased
      significantly intraoperatively. The aEEG voltage did not increase with an
      increase in heart rate. Infants received between 3.7-47 MUg/kg of fentanyl.
      CONCLUSIONS: There was no correlation between aEEG voltage and vital sign
      changes. aEEG is not a useful tool as a marker of pain during patent ductus
      arteriosus ligation, rather a more standardized approach to pain management
      should be considered.

PMID- 23859856
TI  - Corpus callosum measurements correlate with developmental delay in Smith-Lemli
      Opitz syndrome.
AB  - BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation,
      neurodevelopmental disorder of cholesterol metabolism caused by mutations in 7
      dehydrocholesterol reductase. Corpus callosum (CC) malformations and
      developmental delay are common, but the relation between the two has not been
      evaluated. This study hypothesizes shorter callosal length and smaller area
      correlate with higher serum 7-dehydrocholesterol and increased severity of
      neurodevelopmental delay in SLOS. METHODS: Thirty-six individuals with SLOS
      (18M/18F) between 0.20 and 12.5 years (mean = 3.9, SD = 3.6) and 36 typically
      developing controls (18 boys and 18 girls) between 0.12 and 12.8 years (mean =
      4.0, SD = 3.6) were each imaged once on a 1.5T scanner. One midsagittal image per
      study was selected for manual CC measurement. Gross motor, fine motor, and
      language developmental quotients; anatomical severity score; and serum sterol
      levels were assessed. RESULTS: Shorter CC length and smaller area correlated with
      a lower developmental quotient in gross motor and language domains. Furthermore,
      length and area negatively correlated with a serum sterol precursors and severity
      score, and positively correlated with total cholesterol. Degree of developmental
      delay ranged from mild to severe, involving all domains. CONCLUSIONS: For
      individuals with SLOS, smaller callosal area and length are associated with
      higher 7-dehydrocholesterol, severity scores, and developmental delay. The
      relationship between callosal development and biochemical abnormalities in this
      cohort may lead to further studies supporting imaging biomarkers.

PMID- 23859857
TI  - Cerebral magnetic resonance imaging findings in children born extremely preterm,
      very preterm, and at term.
AB  - BACKGROUND: The aim of this study was to compare findings on cerebral MRI scans
      of infants born extremely preterm (i.e., gestation < 28 weeks, very preterm;
      gestation 28-31 weeks) and at term. METHODS: MRI scans obtained in a cohort of 29
      extremely preterm children at 11 years, 51 very preterm young adults at 19 years,
      and respective term-born controls were scored according to presence and degree of
      MRI pathology. RESULTS: MRI pathology was found in 76% of the extremely preterm
      children vs 31% of their controls (odds ratio 4.3; 95% confidence interval, 1.5
      137.5) and in 55% of the very preterm group vs 19% of their controls (odds ratio
      5.2; 95% confidence interval, 2.5-10.9). The distribution of moderate and severe
      pathology did not differ among the groups. CONCLUSIONS: The extremely preterm,
      very preterm, and term subjects shared the same morphological pathology,
      revealing no specific preterm MRI pattern, but both premature cohorts had higher
      frequencies. Differences were mainly limited to mild pathology. Whether MRI
      lesions were more common in the extremely preterm than in the very preterm group
      is uncertain as the difference in frequency was similar in the two control
      groups, suggesting a lack of objective criteria for differentiating mild
      pathology from normality or that MRI scans normally differ at 11 and 19 years of
      age.

PMID- 23859858
TI  - Five novel mutations in ARG1 gene in Chinese patients of argininemia.
AB  - BACKGROUND: Argininemia is an autosomal recessive genetic disorder caused by
      hepatocyte arginase deficiency. It could be detected by blood amino acids
      analysis (high arginine) and confirmed by molecular diagnosis. The clinical
      manifestations in patients are similar to cerebral palsy so the diagnosis is
      usually much delayed. Reports of argininemia from mainland China are few, and
      genetic analyses have not been reported. PATIENTS AND METHODS: Five Chinese
      patients with argininemia were investigated. They had progressive spastic
      tetraplegia, poor physical growth from 1 month to 4 years. When argininemia was
      found at the ages of 4 to 12 years, four of patients had mental retardation, and
      three had seizures. RESULTS: Elevated blood arginine and significantly decreased
      erythrocyte arginase activity in five patients confirmed the diagnosis of
      arginase deficiency. Liver dysfunction was found in four patients, two of whom
      had mildly elevated blood ammonia levels. Cranial magnetic resonance imaging
      showed progressive cerebral atrophy in three patients. Six mutations in the ARG1
      gene were identified, of which only one (c.703 G>A, p.G235R) in exon 7 has been
      reported before; c.34 G>T (p.G12X) in exon 1, c.67delG (p.G23fsX31) in exon 2,
      c.539G>C (p.R180 T) in exon 5, c.374C>T (p.A125 V) in exon 4, and c.646-649del
      CTCA (p.T215fsX219) in exon 6 were novel mutations. CONCLUSIONS: Argininemia is
      one of the few treatable causes of pediatric spastic paraparesis. Early metabolic
      investigation is very important to reach a diagnosis and better outcome. Five
      Chinese patients with late-diagnosed argininemia were reported. The mutation
      spectrum of ARG1 gene should be different from other populations.

PMID- 23859859
TI  - Atypical features in MECP2 P152R-associated Rett syndrome.
AB  - BACKGROUND: Rett syndrome is a neurodevelopmental disorder that occurs in
      individuals with a mutation in the X-linked methyl-CpG-binding protein 2 (2MECP2)
      gene. 2MECP2 mutations produce a high degree of variability in the clinical
      phenotypes including the classic Rett features of head growth deceleration,
      psychomotor regression, deviant communicative ability, hand stereotypes,
      autonomic dysfunction, and seizures. Atypical forms of Rett such as those with
      preserved speech do not follow these characteristics. PATIENT: We report a 9-year
      old girl with atypical Rett (macrocephaly, preserved speech, and psychiatric
      manifestations) with a 2MECP2 (P152R) mutation that generally is not associated
      with these clinical signs. CONCLUSION: This case broadens the genotype-phenotype
      correlation between the P152R mutation 2MECP2-associated Rett syndrome.

PMID- 23859860
TI  - Sequential MR angiography in childhood primary angiitis of the CNS.
AB  - Central nervous system (CNS) vasculitis is rare in childhood. Diagnosis is
      sometimes difficult, and imaging methods range from MRI to MRA to conventional
      angiography. In doubtful cases a brain biopsy is necessary for diagnostic
      purposes. We describe a 6-year old child affected with primary angiitis of the
      CNS who was treated successfully with corticosteroids and mycophenolate mofetil
      and who was followed with MRI and MRA, which guided treatment decisions
      throughout the disease course. Sequential images are shown. 

PMID- 23859861
TI  - Call-Fleming syndrome: headache in a 16-year-old girl.
AB  - BACKGROUND: Call-Fleming syndrome, also known as reversible cerebral
      vasoconstriction syndrome, is an important cause of severe headache characterized
      by segmental constriction of cerebral arteries in multiple vascular
      distributions. It is commonly described in adults, with a female predominance.
      PATIENT: We report a case of a 16-year-old girl with history of anxiety,
      attention deficit hyperactivity disorder, and migraines on several medications
      presenting with 2 weeks of worsening headaches. RESULTS: Cranial computed
      tomography was normal, but magnetic resonance imaging revealed cortical
      subarachnoid hemorrhage. Follow-up imaging demonstrated extensive
      vasoconstriction of small- to medium-sized cerebral arteries. Sertraline and
      methylphenidate were discontinued, and nifedipine was started. Symptoms rapidly
      improved, and repeat angiography at 2 months showed no vasoconstriction.
      CONCLUSIONS: Call-Fleming syndrome is an important cause of thunderclap headache
      and should be considered in the pediatric population, especially in the setting
      of certain medication usage and other known risk factors.

PMID- 23859862
TI  - Arrhythmogenic channelopathy syndromes presenting as refractory epilepsy.
AB  - BACKGROUND: Children and young adults with potentially lethal cardiac
      channelopathies often present to medical care with a history of syncope or
      seizures due to episodic ventricular arrhythmias and associated cerebral
      hypoperfusion. METHODS: Two important types of genetic arrhythmia syndromes-long
      QT syndrome and catecholaminergic polymorphic ventricular tachycardia-are
      discussed using relevant case examples. The pathophysiology and distinguishing
      clinical features of these conditions are reviewed. RESULTS: The patients in each
      case were ultimately diagnosed with a cardiac channelopathy as the cause for
      their syncope and refractory seizures. With appropriate medical management, no
      further events have occurred to date. CONCLUSIONS: Cardiac channelopathies can be
      misdiagnosed as refractory epilepsy when in fact these events represent
      convulsive syncopes. Knowledge of and suspicion for these arrhythmogenic
      conditions may expedite diagnosis and improve outcomes.

PMID- 23859863
TI  - Central retinal artery occlusion in a 13-year-old child as a presenting sign of
      hyperhomocysteinemia together with high lipoprotein(a) level.
AB  - BACKGROUND: We describe a child with central retinal artery occlusion and
      hyperhomocysteinemia. METHODS: A 13-year-old girl developed sudden vision loss
      and was hospitalized for diagnosis and treatment. RESULTS: Her physical
      examination was normal except for her ophthalmologic examination. Her serum
      homocysteine level and lipoprotein(a) were elevated to 45.27 MUmol/L and 61 mg/dL
      0-29 mg/dL, respectively. A homozygous mutation was identified for
      methylenetetrahydrofolate reductase at position C677T. CONCLUSION: This report
      documents central retinal artery occlusion associated with the risk factors of
      hyperhomocysteinemia caused by methylenetetrahydrofolate reductase C677 T
      mutation and high lipoprotein(a) level in a child. Retinal artery occlusion is
      rare in children. This patient emphasizes the need for a systemic evaluation for
      hyperhomocysteinemia and lipoprotein(a) levels in children with retinal vascular
      occlusion of uncertain etiology.

PMID- 23859864
TI  - Butterfly hemorrhage across the corpus callosum.

PMID- 23859865
TI  - Head turning associated with involuntary gaze deviation.

PMID- 23859866
TI  - Phenytoin-induced stuttering: an extremely rare association.

PMID- 23859867
TI  - A novel mutation in HPRT1 gene causing variant form of Lesch-Nyhan disease.

PMID- 23859868
TI  - Impact of sickle cell disease and thalassemias in infants on birth outcomes.
AB  - OBJECTIVE: The contribution of sickle cell disease (SCD) and other common
      thalassemias in infants to adverse birth outcomes is under-studied. We therefore
      sought to compare adverse birth outcomes in infants with and without
      hemoglobinopathy. STUDY DESIGN: Retrospective cohort study utilizing a population
      based dataset from Florida (1998-2007, n=1,564,038). The primary outcomes were
      low birthweight (LBW), very low birthweight (VLBW), preterm birth (PTB), very
      preterm birth (VPTB) and small for gestational age (SGA). We used propensity
      scores to match infants with hemoglobinopathy to those without hemoglobinopathy
      on selected variables. To approximate relative risks, we generated adjusted odds
      ratios (AOR) and 95% confidence intervals (CI) from logistic regression models
      and accounted for the matched design using generalized estimating equations
      framework. RESULTS: Infants with SCD or thalassemia had a heightened risk for LBW
      (AOR=1.58, 95% CI: 1.29-1.93), VLBW (AOR=3.01, 95% CI: 2.12-4.25), PTB (AOR=1.36,
      95% CI: 1.12-1.65), VPTB (AOR=2.70, 95% CI: 1.93-3.78), and neurological
      conditions (AOR=2.04, 95% CI: 1.48-2.81) compared to infants without
      hemoglobinopathy. CONCLUSION: Infants with SCD or thalassemia experience
      considerably higher risks for multiple infant morbidities. Our findings are
      potentially important in prenatal counseling, as well as for targeted care of
      affected pregnancies in the prenatal period.

PMID- 23859870
TI  - Geniposide inhibits airway inflammation and hyperresponsiveness in a mouse model
      of asthma.
AB  - Our group recently reported the strong anti-inflammatory effects of geniposide
      (Gen), a bioactive iridoid glucoside derived from gardenia jasminoides, in a
      mouse acute lung injury model. Herein, we hypothesized that Gen might also have
      potential therapeutic benefits in treatment of asthma, which was tested in a
      mouse model of ovalbumin (Ova)-induced allergic airway inflammation. Ova
      sensitized and -challenged BALB/c mice, as compared with control animals,
      displayed airway hyperresponsiveness (AHR), bronchoalveolar lavage eosinophilia,
      mucus hypersecretion, and increased T help 2 (Th2)-associated cytokine and
      chemokine amounts, as well as serum Ova-specific immunoglobulin E (IgE) level.
      Being compared with the Ova-induced hallmarks of asthma, intraperitoneal Gen
      treatment prevented eosinophilic pulmonary infiltration, attenuated the increases
      in interleukin (IL)-4, IL-5, and IL-13, and reduced eotaxin and vascular cell
      adhesion molecule 1 (VCAM-1) expression. Also, Gen significantly ameliorated the
      Ova-driven airway hyperresponsiveness, mucus hypersecretion, and allergen
      specific IgE level, which are the cardinal pathophysiological symptoms in
      allergic airway diseases. In addition, the efficacy of Gen was comparable to that
      of dexamethasone (Dex), a currently available anti-asthmatic drug. Collectively,
      our findings reveal that the development of immunoregulatory strategies based on
      Gen may be considered as an effective adjuvant therapy for allergic asthma. 

PMID- 23859869
TI  - Mycoepoxydiene inhibits antigen-stimulated activation of mast cells and
      suppresses IgE-mediated anaphylaxis in mice.
AB  - Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated
      with mangrove forest. It has been shown that MED has many kinds of effects such
      as anti-cancer and anti-inflammatory activities. However, its effects on
      anaphylaxis are still unknown. Mast cells play a pivotal role in IgE-mediated
      allergic response. Aggregation of the high affinity IgE receptor (FcepsilonRI) on
      the surface of mast cell activates a cascade of signaling events leading to the
      degranulation and cytokine production in mast cells. Our study showed that MED
      could significantly suppress antigen-stimulated degranulation and cytokine
      production in mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in
      mice. Furthermore, we found that MED suppressed antigen-induced activation of
      Syk, and subsequently inhibited the phosphorylation of PLCgamma1, Akt, and MAPKs
      such as extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase
      (JNK), and p38 in mast cells. Collectively, our study demonstrates that MED can
      inhibit the activation of mast cells and protect mice from mast cell-mediated
      allergic response through inhibiting the activation of Syk. These results suggest
      that MED is a potential compound for developing a promising anti-anaphylaxis
      drug. 

PMID- 23859871
TI  - Schizandrin C exerts anti-neuroinflammatory effects by upregulating phase II
      detoxifying/antioxidant enzymes in microglia.
AB  - We investigated the anti-neuroinflammatory properties of schizandrin C by
      focusing on its roles in the induction of phase II detoxifying/antioxidant
      enzymes and in the modulation of upstream signaling pathways. Schizandrin C
      induced expression of phase II detoxifying/antioxidant enzymes including heme
      oxygenase-1 (HO-1) and NADPH dehydrogenase quinone-1 (NQO-1). Activation of
      upstream signaling pathways, such as the cAMP/protein kinase A/cAMP response
      element-binding protein (cAMP/PKA/CREB) and erythroid-specific nuclear factor
      regulated factor 2 (Nrf-2) pathways, significantly increased following treatment
      with schizandrin C. In addition, expressions of schizandrin C-mediated phase II
      detoxifying/antioxidant enzymes were completely attenuated by adenylyl cyclase
      inhibitor (ddAdo) and protein kinase A (PKA) inhibitor (H-89). In microglia,
      schizandrin C significantly inhibited lipoteichoic acid (LTA)-stimulated pro
      inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide
      (NO), and reactive oxygen species (ROS) production, and inducible nitric oxide
      synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metallopeptidase-9 (MMP-9)
      protein expressions. Moreover, schizandrin C suppressed LTA-induced nuclear
      factor-kappa B (NF-kappaB), activator protein-1 (AP-1), janus-kinase/signal
      transducer and activator of transcription (JAK-STATs), and mitogen-activated
      protein kinase (MAPK) activation. Schizandrin C also effectively suppressed ROS
      generation and NO production, as well as iNOS promoter activity in LTA-stimulated
      microglia. This suppressive effect was reversed by transfection with Nrf-2 and HO
      1 siRNA and co-treatment with inhibitors ddAdo and H-89. Our results indicate
      that schizandrin C isolated from Schisandra chinensis could be used as a natural
      anti-neuroinflammatory agent, inducing phase II detoxifying/antioxidant enzymes
      via cAMP/PKA/CREB and Nrf-2 signaling. 

PMID- 23859872
TI  - Indeterminate pediatric thyroid fine needle aspirations: a study of 68 cases.
AB  - OBJECTIVE: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)
      provides a reporting scheme for thyroid fine needle aspiration (FNA) and includes
      three indeterminate categories with different management strategies. This study
      analyzes indeterminate thyroid FNAs in children, and correlates these findings
      with the histological features. METHODS: A total of 179 thyroid FNA specimens
      were retrieved from children. Cases were categorized by TBSRTC. Only cases
      diagnosed as atypia (AUS)/follicular lesion of undetermined significance (FLUS),
      suspicious for follicular or oncocytic neoplasm (SFON), or suspicious for
      malignancy (SM) were selected and correlated with the nodule size and
      histological follow-up. RESULTS: Sixty-eight cases were identified, including 43
      (63%) AUS/FLUS diagnoses, 19 (28%) SFON, and 6 (9%) SM. On follow-up, 48% were
      malignant, including 28% AUS/FLUS cases, 58% SFON, and 100% SM. The average size
      of the malignant lesions diagnosed preoperatively as AUS/FLUS was 1.5 cm (range
      0.7-4.5), compared to 3.3 cm (range 1.2-6.6) in SFON and 2.8 cm (range 0.7-3.8)
      in SM. Malignancies included 92% papillary thyroid carcinoma (PTC), 77% of which
      were the follicular variant of PTC (FVPTC) and 8% follicular carcinomas. The
      AUS/FLUS cases were largely due to compromised specimens (49%) and the highest
      malignancy rate occurred in those with cytological atypia (50%). CONCLUSIONS:
      This study shows an incremental risk of malignancy within the indeterminate
      categories using TBSRTC in children. Malignant nodules with a preoperative
      AUS/FLUS diagnosis tended to be smaller than those with a SFON or SM diagnosis,
      and the vast majority of malignancies were PTC, with a high proportion being
      FVPTC.

PMID- 23859873
TI  - Toxicokinetic model assessment on the dechlorination of dietary toxaphene CHB-62
      into CHB-44 in Atlantic salmon (Salmo salar L.).
AB  - European Union legislation on the upper limits of toxaphene in feed and food
      include the congeners CHB-26, CHB-62 and CHB-50 and is set at 50 ug kg-1 feed for
      the sum of these three congeners. However, due to their elevated presence in
      fish, the congeners CHB-40 and CHB-41, CHB-44, and CHB-42 should also be included
      according to the European Food Safety Authority (EFSA) in 2005. Earlier trials
      with model zebra fish have shown in vivo dechlorination of dietary CHB-62 to CHB
      44 and, to a lesser degree, of CHB-50 to CHB-40. Biomagnification patterns of
      Atlantic salmon, fed with technical toxaphene-enriched feeds, indicated that
      Atlantic salmon have a similar dechlorination. In the present study, a serial one
      compartment physiological kinetic model, which includes differentiated growth of
      body components, is used to quantify the contribution of dechlorination to the
      congener-specific fillet accumulation of a mixture of dietary toxaphene congeners
      in Atlantic salmon. The model is assessed from experimental uptake and
      elimination kinetics of Atlantic salmon smolt fed with technical toxaphene for
      122 days followed by a depuration period of 75 days in which the fish were fed
      toxaphene-free control feed. The serial one-compartment model shows that about
      31% of CHB-44 that accumulated in the fillet originated from dietary CHB-62. In
      contrast, dechlorination of CHB-50 into CHB-40 is not significant. The results
      show that previously demonstrated in vivo dechlorination of CHB-62 into CHB-44 in
      zebra fish also occurs in the farmed fish species Atlantic salmon. This
      dechlorination can at least partly explain the relatively elevated CHB-44
      observed in toxaphene fish surveys.

PMID- 23859874
TI  - Synthesis and one-pot tethering of hydroxyl-capped phosphorylcholine onto
      cellulose membrane for improving hemocompatibility and antibiofouling property.
AB  - Tethering of biomimetic phosphorylcholine derivative onto the surface of
      biomedical devices is an effective method for improving hemocompatibility and
      antibiofouling property. Herein, series of novel hydroxyl-capped
      phosphorylcholines (HOPC) with different carbon spacer lengths were first
      synthesized and characterized with element analysis (EA), Fourier transform
      infrared spectroscopy(FTIR), and nuclear magnetic resonance spectroscopy (NMR).
      Then, HOPC (n=5, 2a) was one-pot tethered onto cellulose membrane with
      hexamethylene diisocyanate (HDI) as a coupling agent. The existence of
      phosphorylcholine was demonstrated by water contact angle measurement, attenuated
      total reflection Fourier transform infrared spectroscopy (ATR-FTIR), atomic force
      microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). The
      hemocompatibility and antibiofouling property were evaluated by hemolytic test,
      platelet adhesion, protein adsorption, and Escherichia coli adhesion test. The
      results showed that cellulose membranes tethered with HOPC exhibited excellent
      hemocompatibility featured by low platelet adhesion and fibrinogen adsorption as
      well as antibiofouling property with bacterial adhesion resistance. 

PMID- 23859875
TI  - Properties of amphiphilic oligonucleotide films at the air/water interface and
      after film transfer.
AB  - The self-assembly of amphiphilic hybrid materials containing an oligonucleotide
      sequence at the air/water interface was investigated by means of pressure
      molecular area (Pi-A) isotherms. In addition, films were transferred onto solid
      substrates and imaged using scanning force microscopy. We used oligonucleotide
      molecules with lipid tails, which consisted of a single stranded oligonucleotide
      11 mer containing two hydrophobically modified 5-(dodec-1-ynyl)uracil nucleobases
      (dU11) at the 5'-end of the oligonucleotide sequence. The air/water interface was
      used as confinement for the self-assembling process of dU11. Scanning force
      microscopy of films transferred via Langmuir-Blodgett technique revealed mono-,
      bi- (Pi >= 2 mN/m) and multilayer formation (Pi >= 30 mN/m). The first layer was
      1.6 +/- 0.1 nm thick. It was oriented with the hydrophilic oligonucleotide moiety
      facing the hydrophilic substrate while the hydrophobic alkyl chains faced air. In
      the second layer the oligonucleotide moiety was found to face the air. The second
      layer was found to cover up to 95% of the sample area. Our measurements indicated
      that the rearrangement of the molecules into bi- and multiple bilayers happened
      already at the air/water interface. Similar results were obtained with a second
      type of oligonucleotide amphiphile, an oligonucleotide block copolymer, which was
      composed of an oligonucleotide 11 mer covalently attached at the terminus to
      polypropyleneoxide (PPO).

PMID- 23859876
TI  - Delayed neurovascular dysfunction is alleviated by hydrogen in asphyxiated
      newborn pigs.
AB  - BACKGROUND: The neurovascular unit encompasses the functional interactions of
      cerebrovascular and brain parenchymal cells necessary for the metabolic
      homeostasis of neurons. Previous studies indicated marked but only transient (1-4
      h) reactive oxygen species-dependent neurovascular dysfunction in newborn pigs
      after severe hypoxic/ischemic (H/I) stress contributing to the neuronal injury
      after birth asphyxia. OBJECTIVES: Our major purpose was to determine if
      neurovascular dysfunction would also occur later, at 24 h after a milder H/I
      stress. We also tested if the putative hydroxyl radical scavenger hydrogen (H2)
      exerted neurovascular protection. METHODS: Anesthetized, ventilated piglets were
      assigned to three groups of 9 animals: time control, asphyxia/reventilation with
      air, and asphyxia/reventilation with air +2.1% H2 for 4 h. Asphyxia was induced
      by suspending ventilation for 8 min. Cerebrovascular reactivity (CR) of pial
      arterioles was determined using closed cranial window/intravital microscopy 24 h
      after asphyxia to the endothelium-dependent cerebrovascular stimulus hypercapnia,
      the neuronal function-dependent stimulus N-methyl-D-aspartate (NMDA),
      norepinephrine, and sodium nitroprusside. The brains were subjected to
      histopathology. RESULTS: Hemodynamic parameters, blood gases, and core
      temperature did not differ significantly among the experimental groups. In the
      early reventilation period, the recovery of electroencephalographic activity was
      significantly better in H2-treated animals. Asphyxia/reventilation severely
      attenuated CR to hypercapnia and NMDA; however, reactivity to norepinephrine and
      sodium nitroprusside were unaltered. H2 fully or partially preserved CR to
      hypercapnia or NMDA, respectively. Histopathology revealed modest neuroprotection
      afforded by H2. CONCLUSIONS: Severe stimulus-selective delayed neurovascular
      dysfunction develops and persists even after mild H/I stress. H2 alleviates this
      delayed neurovascular dysfunction that can contribute to its neuroprotective
      effect.

PMID- 23859877
TI  - Effects of harmful dinoflagellate Ostreopsis cf. ovata exposure on immunological,
      histological and oxidative responses of mussels Mytilus galloprovincialis.
AB  - In the last decade massive blooms of the Ostreopsis cf. ovata have occurred in
      the Mediterranean basin, posing great concern to both environmental and human
      health. Biotoxicological and chemical studies demonstrated that O. cf. ovata
      produces palytoxin and ovatoxins; besides direct respiratory effects on humans
      due to inhalation of marine toxic aerosols, O. cf. ovata blooms can cause adverse
      effects on benthic invertebrates. The main aim of this study was to highlight the
      role of immunological, cellular and oxidative mechanisms in modulating the
      toxicity induced by O. cf. ovata in mussels Mytilus galloprovincialis. Organisms
      were exposed in laboratory condition to O. cf. ovata and analysed after 7 and 14
      days of exposure. Obtained results demonstrated a clear involvement of the immune
      system with a significant decrement of granulocytes respect to the hyalinocytes
      type cells, a diminished phagocytosis activity and a reduced lysosomal membrane
      stability in haemocytes, after both 7 and 14 days of exposure. Histological
      analyses showed a decrease of the digestive gland wall thickness, dilatation of
      the tubules, haemocytes infiltration into the digestive gland and a decrement of
      neutral lipid levels in exposed mussels; similar results suggest a possible
      inhibition of the feeding activity, with a consequent induction of authophagic
      phenomena and utilization of stored reserve products such as neutral lipids.
      Antioxidant parameters revealed a limited role of O. cf. ovata to induce
      oxidative stress in mussels exposed under laboratory conditions excepting for a
      certain increase of catalase, glutathione reductase and glutathione peroxidases
      activities, and a significantly higher capability to neutralize peroxyl radicals
      in mussels exposed for 14 days. Although the obtained results suggest a non
      specific response of mussels to the O. cf. ovata exposure, observed effects on
      the general health status of exposed mussels should be adequately considered when
      assessing the ecological relevance of these algal blooms.

PMID- 23859878
TI  - A comparative study: In vitro effects of EPA and DHA on immune functions of head
      kidney macrophages isolated from large yellow croaker (Larmichthys crocea).
AB  - Comparative effects of different concentrations of eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA) on immune responses of head-kidney macrophages
      isolated from large yellow croaker were studied in vitro. After exposing to serum
      free medium for 1 day, cultured cells were incubated in medium supplemented with
      graded levels of EPA or DHA (0, 5, 25, 100, 200 and 1000 MUM, respectively) in
      the form of fatty acid bovine serum albumin (FA-BSA) complex for 12 h, 24 h and
      36 h, respectively. Control samples were incubated in the absence of EPA or DHA
      (2% bovine serum albumin, BSA). Following stimulation, cell viability, lipid
      peroxidation, secretary phopholipase A2 (sPLA2) and prostaglandin E2 (PGE2)
      production as well as some immune parameters including phagocytosis, respiratory
      burst activity and interleukin 1beta (IL-1beta) production were determined.
      Results showed that EPA and DHA affected cell viability in dose-dependent and
      time-dependent manners. In particular, cell viability was significantly decreased
      after 24 h and 36 h incubation with 1000 MUM EPA or DHA (P < 0.05). Higher levels
      of EPA (200 and 1000 MUM) caused a significant increase in the production of
      malondialdehyde (MDA) (P < 0.05), while DHA did not significantly affect the MDA
      production. EPA significantly increased the intracellular superoxide anion
      synthesis which, on the contrary, was significantly reduced by DHA. Phagocytosis
      percentage (PP) values were significantly higher in treatments with 5 MUM DHA (P
      < 0.05), but significantly decreased by 200 and 1000 MUM EPA and DHA compared to
      the control group (P < 0.05). Decreased PGE2 production was produced by cells
      treated with relatively low doses of EPA or DHA. When high levels of stimulants
      (1000 MUM EPA or DHA) were used, PGE2 levels were elevated and reached a
      significant level (P < 0.05). Both EPA and DHA significantly inhibited the
      production of sPLA2, where DHA exerted the more potent inhibitory effects than
      EPA. No pronounced effect was observed on IL-1beta production among all the
      treatments, and IL-1beta level in cell culture supernatant was fairly low (only
      approximately 6 pg/ml). Those findings suggested that EPA and DHA could influence
      the immunity and physiological conditions of macrophages from head kidney of
      large yellow croaker in vitro.

PMID- 23859879
TI  - Kazal-type proteinase inhibitor from disk abalone (Haliotis discus discus):
      molecular characterization and transcriptional response upon immune stimulation.
AB  - Proteinases and proteinase inhibitors are involved in several biological and
      physiological processes in all multicellular organisms. Proteinase inhibitors
      play a key role in regulating the activity of the respective proteinases. Among
      serine proteinase inhibitors, kazal-type proteinase inhibitors (KPIs) are widely
      found in mammals, avians, and a variety of invertebrates. In this study, we
      describe the identification of a kazal-type serine proteinase inhibitor (Ab-KPI)
      from the disk abalone, Haliotis discus discus, which is presumably involved in
      innate immunity. The full-length cDNA of Ab-KPI includes 600 bp nucleotides with
      an open reading frame (ORF) encoding a polypeptide of 143 amino acids. The
      deduced amino acid sequence of Ab-KPI contains a putative 17-amino acid signal
      peptide and two tandem kazal domains with high similarity to other kazal-type
      SPIs. Each kazal domain consists of reactive site (P1) residue containing a
      leucine (L), and a threonine (T) located in the second amino acid position after
      the second conserved cysteine of each domain. Temporal expression of Ab-KPI was
      assessed by real time quantitative PCR in hemocytes and mantle tissue following
      bacterial and viral hemorrhagic septicemia virus (VHSV) challenge, and tissue
      injury. At 6 h post-bacterial and -VHSV challenge, Ab-KPI expression in hemocytes
      was increased 14-fold and 4-fold, respectively, compared to control samples. The
      highest up-regulations upon tissue injury were shown at 9 h and 12 h in hemocytes
      and mantle, respectively. The transcriptional modulation of Ab-KPI following
      bacterial and viral challenges and tissue injury indicates that it might be
      involved in immune defense as well as wound healing process in abalone.

PMID- 23859880
TI  - Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal
      phenotypes in rats and mice.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      which plays a role in the development of multiple tissues and is activated by a
      large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In
      order to examine the roles of the AHR in both normal biological development and
      response to environmental chemicals, an AHR knockout (AHR-KO) rat model was
      created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either
      2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague
      Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats
      harboring either mutation type lacked expression of AHR protein in the liver. AHR
      KO rats were also insensitive to thymic involution, increased hepatic weight and
      the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following
      acute exposure to 25 MUg/kg TCDD. AHR-KO rats had lower basal expression of
      transcripts for these genes and also accumulated ~30-45-fold less TCDD in the
      liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO
      rats, had alterations in serum analytes indicative of compromised hepatic
      function, patent ductus venosus of the liver and persistent hyaloid arteries in
      the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to
      the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary
      tubular and uroepithelial degenerative changes and bilateral ureter dilation
      (hydroureter). The present data indicate that the AHR may play significantly
      different roles in tissue development and homeostasis and toxicity across rodent
      species.

PMID- 23859882
TI  - Ruptured cerebral aneurysm and acute bilateral carotid artery dissection in a
      patient with polycystic kidney disease and polycystic liver disease.

PMID- 23859881
TI  - In utero and early life arsenic exposure in relation to long-term health and
      disease.
AB  - BACKGROUND: There is a growing body of evidence that prenatal and early childhood
      exposure to arsenic from drinking water can have serious long-term health
      implications. OBJECTIVES: Our goal was to understand the potential long-term
      health and disease risks associated with in utero and early life exposure to
      arsenic, as well as to examine parallels between findings from epidemiological
      studies with those from experimental animal models. METHODS: We examined the
      current literature and identified relevant studies through PubMed by using
      combinations of the search terms "arsenic", "in utero", "transplacental",
      "prenatal" and "fetal". DISCUSSION: Ecological studies have indicated
      associations between in utero and/or early life exposure to arsenic at high
      levels and increases in mortality from cancer, cardiovascular disease and
      respiratory disease. Additional data from epidemiologic studies suggest
      intermediate effects in early life that are related to risk of these and other
      outcomes in adulthood. Experimental animal studies largely support studies in
      humans, with strong evidence of transplacental carcinogenesis, atherosclerosis
      and respiratory disease, as well as insight into potential underlying mechanisms
      of arsenic's health effects. CONCLUSIONS: As millions worldwide are exposed to
      arsenic and evidence continues to support a role for in utero arsenic exposure in
      the development of a range of later life diseases, there is a need for more
      prospective studies examining arsenic's relation to early indicators of disease
      and at lower exposure levels.

PMID- 23859883
TI  - Overturning established chemoselectivities: selective reduction of arenes over
      malonates and cyanoacetates by photoactivated organic electron donors.
AB  - The prevalence of metal-based reducing reagents, including metals, metal
      complexes, and metal salts, has produced an empirical order of reactivity that
      governs our approach to chemical synthesis. However, this reactivity may be
      influenced by stabilization of transition states, intermediates, and products
      through substrate-metal bonding. This article reports that in the absence of such
      stabilizing interactions, established chemoselectivities can be overthrown. Thus,
      photoactivation of the recently developed neutral organic superelectron donor 5
      selectively reduces alkyl-substituted benzene rings in the presence of activated
      esters and nitriles, in direct contrast to metal-based reductions, opening a new
      perspective on reactivity. The altered outcomes arising from the organic electron
      donors are attributed to selective interactions between the neutral organic
      donors and the arene rings of the substrates. 

PMID- 23859884
TI  - Online prevention aimed at lifestyle behaviors: a systematic review of reviews.
AB  - BACKGROUND: Interventions aimed at behavior change are increasingly being
      delivered over the Internet. Although research on intervention effectiveness has
      been widely conducted, their true public health impact as indicated by reach,
      effectiveness, and use is unclear. OBJECTIVE: The aim of this paper is to (1)
      review the current literature on online prevention aimed at lifestyle behaviors,
      and (2) identify research gaps regarding reach, effectiveness, and use. METHODS:
      A systematic search in PubMed revealed relevant literature published between 2005
      and 2012 on Internet-delivered behavior change interventions aimed at dietary
      behaviors, physical activity, alcohol use, smoking, and condom use. Our search
      yielded 41 eligible reviews, which were analyzed in terms of reach,
      effectiveness, and use according to the RE-AIM framework. RESULTS: According to
      health priorities, interventions are largely targeted at weight-related
      behaviors, such as physical activity and dietary behavior. Evaluations are
      predominantly effect-focused and overall effects are small, variable, and not
      sustainable. Determinants of effectiveness are unclear; effectiveness cannot yet
      be unambiguously attributed to isolated elements. Actual reach of interventions
      is undiversified, mostly reaching participants who are female, highly educated,
      white, and living in high-income countries. One of the most substantial problems
      in online prevention is the low use of the interventions, a phenomenon seen
      across all behavior domains. CONCLUSIONS: More research is needed on effective
      elements instead of effective interventions, with special attention to long-term
      effectiveness. The reach and use of interventions need more scientific input to
      increase the public health impact of Internet-delivered interventions.

PMID- 23859885
TI  - Does gender influence participation? Predictors of participation in a community
      health worker diabetes management intervention with African American and Latino
      adults.
AB  - PURPOSE: The purpose of the study was to determine the effects of gender on
      participation in a community-based, culturally tailored diabetes lifestyle
      intervention, led by trained community health workers (CHW) and conducted with
      African Americans and Latinos with type 2 diabetes. METHODS: This study utilized
      data collected from 180 participants. Multivariable binary and cumulative
      logistic regression models were used to analyze associations between gender and
      race/ethnicity with study completion and participation in 3 aspects of the
      intervention: group classes, CHW home visits, and CHW-accompanied doctor visits.
      RESULTS: Among Latinos, men were less likely than women to complete the study,
      attend group classes, and complete CHW home visits. There were no gender
      differences in participation seen among African Americans. CONCLUSIONS: Diabetes
      management interventions may need to adapt their designs to optimize retention
      and participation of Latino men. Among African American men, the CHW model may be
      promising. Reasons for low participation among Latino men should receive more
      study. Future studies should assess whether similar findings apply in other
      communities and populations.

PMID- 23859886
TI  - The "squeeze and wheeze" sign: a useful clinical sign in lung sounds analysis of
      children with acute cough.

PMID- 23859887
TI  - Face, content and concurrent validity of the Mimic(r) dV-Trainer for robot
      assisted endoscopic surgery: a prospective study.
AB  - OBJECTIVE: The aim of this study was to determine whether any correlation exists
      between the performance of the Mimic(r) dV-Trainer (Mimic Technologies, Seattle,
      Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale,
      Calif., USA). METHODS: Twelve participants were recruited, ranging from residents
      to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg
      Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the
      Mimic dV-Trainer. The performance of the participants was recorded and measured.
      Additionally, we prepared the same tasks for the da Vinci Surgical System. All
      participants completed the tasks using the da Vinci Surgical System and were
      assessed according to time, the Objective Structured Assessment of Technical
      Skill checklist and the global rating score for endoscopic suturing assessed by
      two independent blinded observers. After performing these tasks, the participants
      completed a questionnaire that evaluated the Mimic dV-Trainer's face and content
      validity. The final results for each participant for the Mimic dV-Trainer and the
      da Vinci Surgical System were compared. RESULTS: All participants ranked the
      Mimic dV-Trainer as a realistic training platform that is useful for residency
      training. There was a significant relationship between the Mimic dV-Trainer and
      the da Vinci Surgical System in all four tasks. We verified the reliability of
      the assessment of the checklist and the global rating scores for endoscopic
      suturing assessed by the two blinded observers using Cronbach's alpha test (r =
      0.803, 0.891). CONCLUSIONS: We evaluated the concurrent validity of the Mimic dV
      Trainer and the da Vinci Surgical System. Our results suggest the possibility
      that training using the Mimic dV-Trainer may therefore be able to improve the
      operator's performance during live robot-assisted surgery.

PMID- 23859888
TI  - Effects of cold-pressor and mental arithmetic on pupillary light reflex.
AB  - Dynamic pupillary light reflex (PLR) is a simple neurological test that can be
      useful for assessment of autonomic disorders. In this study, we investigated the
      changes in PLR induced by mental arithmetic task and cold pressor trials which
      are often applied in research as model systems to elicit autonomic responses. PLR
      was recorded before, during and after mental arithmetic and cold pressor tasks in
      20 healthy adults (ten males and ten females). Stress-induced sympathetic
      activation was evident as shown in the increased blood pressure during both
      tasks. Although the pupillary constriction amplitude did not show significant
      changes, both constriction time and redilation time changed during the tasks. A
      significant gender effect was observed in cold pressor that suggested more
      sympathetic activation in males and faster parasympathetic activation in females
      in response to light stimulation under cold pressor. 

PMID- 23859889
TI  - Effects of coupled upper limbs movements on postural stabilisation.
AB  - The preference for in-phase association of coupled cyclic limbs movements is well
      described (mirror-symmetrical patterns) and this is demonstrated by the ease of
      performing in-phase movements compared to anti-phase ones. The hypothesis of this
      study is that the easiest movement patterns are those with minor postural
      activity. The aim of this study was to describe postural activity in standing
      subjects in the sagittal and frontal planes during the execution of three upper
      limbs tasks (single arm, in-phase, anti-phase) at four different frequencies
      (from 0.6 to 1.2Hz). We employed six infrared cameras for recording kinematics
      information, a force platform for measuring forces exerted on the ground, and a
      system for surface electromyography (SEMG). Outcome measures were: upper limb
      range of movement and relative-phase, centre of pressure displacement (COP),
      screw torque (Tz) exerted on the ground, and SEMG recordings of postural muscles
      (adductor longus, gluteus medius, rectus femoris, and biceps femoris). Our
      results show that in both the planes the in-phase task resulted in less COP
      displacement, torque production, and postural muscles involvement than the anti
      phase and single arm tasks. This reduced need of postural control could explain
      the ease of performing in-phase coupled limb movements compared with anti-phase
      movements. 

PMID- 23859891
TI  - Prediction of alcohol and gambling problems in young adults by using a measure of
      decision making.
AB  - OBJECTIVES: Individuals who regularly gamble, regularly consume alcohol, or meet
      criteria for an alcohol-use disorder or pathological gambling may make riskier
      decisions on cognitive tasks. What remains unclear in the literature is whether
      these decision-making deficits precede or result from these addictive behaviors.
      This study aimed to determine whether risky decision making on a cognitive task
      is predictive of increasing gambling behaviors and alcohol use. METHODS: Fifty
      eight young adults (aged 18-29 years) free from Axis I disorders and reporting no
      symptoms of at-risk gambling behavior or alcohol consumption, who were
      participating in a longitudinal study of impulsivity, were grouped as either high
      risk decision makers (n = 29) or low-risk decision makers (n = 29) by using the
      Cambridge Gamble Task. Subjects were assessed at 1-year follow-up to examine
      gambling frequency, alcohol consumption, at-risk alcohol-use criteria, alcohol
      use disorder criteria, at-risk gambling criteria, and pathological gambling
      criteria. RESULTS: High-risk decision makers were found to be more likely to meet
      at-risk criteria for alcohol use after 1 year. Decision-making group membership
      was not significantly correlated with frequency of gambling or development of
      pathological gambling or alcohol-use disorder over 1 year. CONCLUSIONS: A
      variable measuring risky decision making on the Cambridge Gambling Task may be
      able to predict who is more likely to increase alcohol use per session later in
      life.

PMID- 23859892
TI  - Quantum dynamics with sparse grids: a combination of Smolyak scheme and cubature.
      Application to methanol in full dimensionality.
AB  - Quantum dynamical approaches based on product-grids are limited to the studies of
      molecular systems with few degrees of freedom, typically less than ten. Recently,
      Avila et al. [G. Avila, T. Carrington, J. Chem. Phys., 131 (2009) 174103] have
      introduced the Smolyak scheme [S.A. Smolyak, Sov. Math. Dokl., 4 (1963) 240],
      which considerably reduces the size of the grids. This approach has pushed back
      the present calculation limits on the vibrational spectra of polyatomic
      molecules. In the present study, we have developed an extension of the standard
      Smolyak scheme in which this scheme is combined with multidimensional grids, such
      as cubatures, to obtain new sparse grids. This scheme has been applied to the
      study of the torsional energy levels of methanol in full dimensionality (12D). 

PMID- 23859890
TI  - Colonize, evade, flourish: how glyco-conjugates promote virulence of Helicobacter
      pylori.
AB  - Helicobacter pylori is an adapted gastric pathogen that colonizes the human
      stomach, causing severe gastritis and gastric cancer. A hallmark of infection is
      the ability of this organism to evade detection by the human immune system. H.
      pylori has evolved a number of features to achieve this, many of which involve
      glyco-conjugates including the lipopolysaccharide, peptidoglycan layer,
      glycoproteins, and glucosylated cholesterol. These major bacterial components
      possess unique features from those of other gram-negative organisms, including
      differences in structure, assembly, and modification. These defining
      characteristics of H. pylori glycobiology help the pathogen establish a long
      lived infection by providing camouflage, modulating the host immune response, and
      promoting virulence mechanisms. In this way, glyco-conjugates are essential for
      H. pylori pathogenicity and survival, allowing it to carve out a niche in the
      formidable environment of the human stomach. 

PMID- 23859893
TI  - A survival benefit of major hepatectomy for hepatocellular carcinoma identified
      by preoperative [18F] fluorodeoxyglucose positron emission tomography in patients
      with well-preserved hepatic function.
AB  - AIMS: Hepatic resection can cure hepatocellular carcinoma (HCC). However, the
      optimal extent of resection remains controversial. Major hepatectomy could
      minimize a tumor recurrence, but it is harmful due to decreased hepatic
      functional reserve. [18F] fluorodeoxyglucose positron emission tomography (FDG
      PET) scans are known as their reflection tumor differentiation and biological
      activity in HCC. To evaluate a benefit of major hepatectomy for HCC, we performed
      this retrospective analysis in patients with well-preserved hepatic function, and
      further analyzed in the subset identified by preoperative FDG-PET. METHODS: We
      reviewed the medical records of 189 patients with HCC who underwent curative
      resection between August 2004 and December 2010 at two institutes. All patients
      underwent anatomical resection, either by major or minor hepatectomy. RESULTS:
      Median overall survival did not differ significantly between the major and minor
      hepatectomy groups (29.4 versus 26.3 months, p = 0.269). However, the major
      hepatectomy group had a better recurrence-free survival (24.5 versus 19.9 months,
      p = 0.004). On multivariate analysis, the presence of intrahepatic metastasis
      independently predicted overall survival (p = 0.009), but other examined
      variables did not. Overall survival and recurrence-free survival were
      significantly better following major hepatectomy rather than minor hepatectomy in
      patients whose preoperative FDG-PET indicated that the maximum standardized
      uptake value of the tumor (SUVtumor) was >=4 and the tumor-to-nontumor SUV ratio
      (TNR) was >=1.5. CONCLUSIONS: Our findings suggest that preoperative FDG-PET may
      be useful in identifying patients with favorable hepatic reserve who are most
      likely to benefit from major rather than minor hepatectomy.

PMID- 23859894
TI  - Urinary retention: benefit of gradual bladder decompression - myth or truth? A
      randomized controlled trial.
AB  - INTRODUCTION: Urinary retention is a common emergency requiring immediate
      catheterization. Gradual decompression (GD) of the extended bladder is believed
      to minimize the risk of complications such as bleeding or circulatory collapse,
      but to date it has not been compared with rapid decompression (RD) in controlled
      trials. MATERIALS AND METHODS: Male patients presenting with urinary retention (n
      = 294) were randomized to rapid or gradual catheterization. For the latter, the
      transurethral catheter was clamped for 5 min after every 200-ml outflow until the
      bladder was completely empty. Patients were monitored for at least 30 min
      thereafter with regular checks of vital signs and presence of macroscopic
      hematuria. RESULTS: Of 294 patients, 142 (48.3%) were randomized to the GD and
      152 (51.7%) to the RD group. Both groups showed no statistically significant
      difference with regard to age, anticoagulation treatment, catheter size and
      material, or volume retained. Hematuria occurred in 16 (11.3%) of the GD and 16
      (10.5%) of the RD group; 6 patients in the former and 4 in the latter required
      further treatment. No circulatory collapse occurred. We noted a decrease in the
      previously raised blood pressure and heart rate in both groups, although without
      clinical significance. CONCLUSION: In this first randomized trial, no
      statistically significant difference was noted between gradual and rapid emptying
      of the bladder for urinary retention. Gradual emptying did not reduce the risk of
      hematuria or circulatory collapse. Therefore, there is no need to prefer gradual
      over rapid emptying, which is both easy and safe.

PMID- 23859895
TI  - Evaluation of ultrasound combined with chitosan for the control of weight and
      local fat in mice.
AB  - Ultrasound (US) has recently been used to reduce localized adiposity in humans.
      The study described here evaluated the combined use of chitosan, which is used to
      treat hyperlipidemic diseases and fatty liver, and US to control weight and local
      fat deposition in normal mice over a 5-wk experimental period. Female ICR mice
      were randomly divided into four groups (n = 5 animals per group): (1) control,
      (2) US only, (3) chitosan only and (4) chitosan + US. Body weight, epididymal fat
      pad and intra-abdominal fat thickness (via US imaging) and plasma concentrations
      of high-density lipoprotein cholesterol, triglycerides and low-density
      lipoprotein cholesterol were measured in all mice before and after the 5-wk
      treatment period. After the 5-wk treatment period, weight had decreased
      significantly in the chitosan + US group (-11.2%) compared with the US only (
      5.8%) and chitosan only (-9.3%) groups (p < 0.05). The reduction in epididymal
      fat pad thickness was significantly more marked in the chitosan + US group
      (28.2%) than in the other groups (p < 0.05). Furthermore, in the chitosan + US
      group, plasma levels of triglycerides and low-density lipoprotein cholesterol
      significantly decreased by 51.5% and 26%, respectively. This is the first report
      of effective control of weight and local fat by a combination of ultrasound and a
      putative fat-reducing dietary supplement in mice. The described method
      significantly decreases local fat pad deposition, weight and plasma lipid levels.

PMID- 23859896
TI  - CREANUIS: a non-linear radiofrequency ultrasound image simulator.
AB  - Nonlinear ultrasound methods are widely used in clinical applications for tissue
      or contrast harmonic imaging. Accurate non-linear imaging simulation tools are
      required in research studies for the development of new methods. However, in
      existing simulators, the possible inhomogeneity of the coefficient of non
      linearity, which is generally observed in tissue and in particular when contrast
      agents are involved, has not yet been implemented. This article describes a new
      ultrasound simulator, called CREANUIS, devoted to the computation of B-mode
      images where both linear and non-linear propagation in media is considered, with
      a possible inhomogeneous coefficient of non-linearity. The resulting fundamental
      images, based on a spatially variant and non-linear point spread function, are in
      accordance with those obtained through the reference linear FieldII simulator,
      with computation time reduced by a factor of at least 1.8. Non-linear images of
      media exhibiting inhomogeneous coefficients of non-linearity are also provided.
      The simulation software can be freely downloaded from our website.

PMID- 23859897
TI  - Validation of quantitative structure-activity relationship models to predict
      water-solubility of organic compounds.
AB  - Water-solubility is an important physicochemical property in pharmaceutical and
      environmental studies. We assessed the performance of five predictive computer
      models: ACD/PhysChem History, ADMET Predictor, T.E.S.T., EPI Suite-WSKOWWIN and
      EPI Suite-WATERNT; two of them are commercial, the others are free. We used more
      than 4000 compounds with experimental values to evaluate the models, considering
      the chemicals inside and outside the applicability domain of the models, those
      used to build up the model (training set) and those not present in it (prediction
      set). We also evaluated their ability to predict continuous solubility values,
      and solubility classes. Overall, considering the whole data set, some models gave
      a good statistical performance, with R(2) up to 0.88. 

PMID- 23859898
TI  - Chemical-based risk assessment and in vitro models of human health effects
      induced by organic pollutants in soils from the Olona Valley.
AB  - Risk assessment of soils is usually based on chemical measurements and assuming
      accidental soil ingestion and evaluating induced toxic and carcinogenic effects.
      Recently biological tools have been coupled to chemical-based risk assessment
      since they integrate the biological effects of all xenobiotics in soils. We
      employed integrated monitoring of soils based on chemical analyses, risk
      assessment and in vitro models in the highly urbanized semirural area of the
      Olona Valley in northern Italy. Chemical characterization of the soils indicated
      low levels of toxic and carcinogenic pollutants such as PAHs, PCDD/Fs, PCBs and
      HCB and human risk assessment did not give any significant alerts. HepG2 and
      BALB/c 3T3 cells were used as a model for the human liver and as a tool for the
      evaluation of carcinogenic potential. Cells were treated with soil extractable
      organic matters (EOMs) and the MTS assay, LDH release and morphological
      transformation were selected as endpoints for toxicity and carcinogenicity. Soil
      EOMs induced dose-dependent inhibition of cell growth at low doses and
      cytotoxicity after exposure to higher doses. This might be the result of block of
      cell cycle progression to repair DNA damage caused by oxidative stress; if this
      DNA damage cannot be repaired, cells die. No significant inductions of foci were
      recorded after exposure to EOMs. These results indicate that, although the
      extracts contain compounds with proven carcinogenic potential, the levels of
      these pollutants in the analyzed soils were too low to induce carcinogenesis in
      our experimental conditions. In this proposed case study, HepG2 cells were found
      an appropriate tool to assess the potential harm caused by the ingestion of
      contaminated soil as they were able to detect differences in the toxicity of soil
      EOMs. Moreover, the cell transformation assay strengthened the combined approach
      giving useful information on carcinogenic potential of mixtures. 

PMID- 23859899
TI  - Modifying the Soil and Water Assessment Tool to simulate cropland carbon flux:
      model development and initial evaluation.
AB  - Climate change is one of the most compelling modern issues and has important
      implications for almost every aspect of natural and human systems. The Soil and
      Water Assessment Tool (SWAT) model has been applied worldwide to support
      sustainable land and water management in a changing climate. However, the
      inadequacies of the existing carbon algorithm in SWAT limit its application in
      assessing impacts of human activities on CO2 emission, one important source of
      greenhouse gasses (GHGs) that traps heat in the earth system and results in
      global warming. In this research, we incorporate a revised version of the CENTURY
      carbon model into SWAT to describe dynamics of soil organic matter (SOM)-residue
      and simulate land-atmosphere carbon exchange. We test this new SWAT-C model with
      daily eddy covariance (EC) observations of net ecosystem exchange (NEE) and
      evapotranspiration (ET) and annual crop yield at six sites across the U.S.
      Midwest. Results show that SWAT-C simulates well multi-year average NEE and ET
      across the spatially distributed sites and capture the majority of temporal
      variation of these two variables at a daily time scale at each site. Our analyses
      also reveal that performance of SWAT-C is influenced by multiple factors, such as
      crop management practices (irrigated vs. rainfed), completeness and accuracy of
      input data, crop species, and initialization of state variables. Overall, the new
      SWAT-C demonstrates favorable performance for simulating land-atmosphere carbon
      exchange across agricultural sites with different soils, climate, and management
      practices. SWAT-C is expected to serve as a useful tool for including carbon flux
      into consideration in sustainable watershed management under a changing climate.
      We also note that extensive assessment of SWAT-C with field observations is
      required for further improving the model and understanding potential
      uncertainties of applying it across large regions with complex landscapes. 

PMID- 23859900
TI  - Yeast and bacterial diversity along a transect in an acidic, As-Fe rich
      environment revealed by cultural approaches.
AB  - Acid mine drainages (AMDs) are often thought to harbour low biodiversity, yet
      little is known about the diversity distribution along the drainages. Using
      culture-dependent approaches, the microbial diversity from the Carnoules AMD
      sediment was investigated for the first time along a transect showing progressive
      environmental stringency decrease. In total, 20 bacterial genera were detected,
      highlighting a higher bacterial diversity than previously thought. Moreover, this
      approach led to the discovery of 16 yeast species, demonstrating for the first
      time the presence of this important phylogenetic group in this AMD. All in all,
      the location of the microbes along the transect helps to better understand their
      distribution in a pollution gradient. 

PMID- 23859901
TI  - Dominant form of congenital hyperinsulinism maps to HK1 region on 10q.
AB  - BACKGROUND/AIMS: In a family with congenital hyperinsulinism (HI), first
      described in the 1950s by McQuarrie, we examined the genetic locus and clinical
      phenotype of a novel form of dominant HI. METHODS: We surveyed 25 affected
      individuals, 7 of whom participated in tests of insulin dysregulation (24-hour
      fasting, oral glucose and protein tolerance tests). To identify the disease locus
      and potential disease-associated mutations we performed linkage analysis, whole
      transcriptome sequencing, whole genome sequencing, gene capture, and next
      generation sequencing. RESULTS: Most affecteds were diagnosed with HI before age
      one and 40% presented with a seizure. All affecteds responded well to diazoxide.
      Affecteds failed to adequately suppress insulin secretion following oral glucose
      tolerance test or prolonged fasting; none had protein-sensitive hypoglycemia.
      Linkage analysis mapped the HI locus to Chr10q21-22, a region containing 48
      genes. Three novel noncoding variants were found in hexokinase 1 (HK1) and one
      missense variant in the coding region of DNA2. CONCLUSION: Dominant, diazoxide
      responsive HI in this family maps to a novel locus on Chr10q21-22. HK1 is the
      more attractive disease gene candidate since a mutation interfering with the
      normal suppression of HK1 expression in beta-cells could readily explain the
      hypoglycemia phenotype of this pedigree.

PMID- 23859902
TI  - Breeding aflatoxin-resistant maize lines using recent advances in technologies -
      a review.
AB  - Aflatoxin contamination caused by Aspergillus flavus infection of corn is a
      significant and chronic threat to corn being used as food or feed. Contamination
      of crops at levels of 20 ng g(-1) or higher (as regulated by the USFDA) by this
      toxin and potent carcinogen makes the crop unsalable, resulting in a significant
      economic burden on the producer. This review focuses on elimination of this
      contamination in corn which is a major US crop and the basis of many products.
      Corn is also "nature's example" of a crop containing heritable resistance to
      aflatoxin contamination, thereby serving as a model for achieving resistance to
      aflatoxin contamination in other crops as well. This crop is the largest
      production grain crop worldwide, providing food for billions of people and
      livestock and critical feedstock for production of biofuels. In 2011, the
      economic value of the US corn crop was US$76 billion, with US growers producing
      an estimated 12 billion bushels, more than one-third of the world's supply. Thus,
      the economics and significance of corn as a food crop and the threat to food
      safety due to aflatoxin contamination of this major food crop have prompted the
      many research efforts in many parts of the world to identify resistance in corn
      to aflatoxin contamination. Plant breeding and varietal selection has been used
      as a tool to develop varieties resistance to disease. This methodology has been
      employed in defining a few corn lines that show resistance to A. flavus invasion;
      however, no commercial lines have been marketed. With the new tools of proteomics
      and genomics, identification of resistance mechanisms, and rapid resistance
      marker selection methodologies, there is an increasing possibility of finding
      significant resistance in corn, and in understanding the mechanism of this
      resistance. 

PMID- 23859903
TI  - Health technology assessment of computer-assisted pap test screening in Italy.
AB  - OBJECTIVE: To assess the introduction of computer-assisted Pap test screening in
      cervical cancer screening. Various scenarios are considered: conventional and
      liquid-based cytology (LBC) slides, fully automatic instrumentation (Becton
      Dickinson FocalPointTM Slide Profiler and Hologic ThinPrep(r) Imaging System),
      and semiautomatic scanner (Hologic Integrated Imager I-Squared). METHODS: A
      working group was formed that included researchers from the largest centers
      already using instrumentation. A questionnaire on laboratory management and on
      social/ethical issues and annual workload was proposed. Prices for the technology
      were obtained directly from the producers; costs were calculated from observed
      and literature data. The scope of the report and final draft were submitted to a
      consulting committee of stakeholders. RESULTS: The break-even point was found to
      be 49,000 cases/year, if conventional slides were used, while it was near the
      theoretical maximum capacity, 70,000 cases/year, with LBC slides. Efficiency
      increased with the volume of slides. Screening time decreased by two thirds for
      conventional slides and by less than half for LBC slides. Acceptance of the
      instrumentation by the users was good. CONCLUSIONS: Computer-assisted screening
      may increase productivity even if in most situations it will mean additional
      costs. Furthermore, primary screening with human papillomavirus tests will
      drastically reduce the need for Pap test reading.

PMID- 23859904
TI  - Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in
      Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic
      associations.
AB  - Fusion genes involved in acute lymphoblastic leukemia (ALL) occur mostly due to
      genetic and environmental factors, and only a limited number of studies have
      reported any ethnic influence. This study assesses whether an ethnic influence
      has an effect on the frequency of any of the four fusion genes: BCR-ABL1, ETV6
      RUNX1, TCF3-PBX1, and MLL-AFF1 found in ALL. To study this ethnic influence,
      mononuclear cells were obtained from bone marrow samples from 143 patients with
      ALL. We performed RNA extraction and reverse transcription, then assessed the
      quality of the cDNA by amplifying the ABL1 control gene, and finally evaluated
      the presence of the four transcripts by multiplex polymerase chain reaction. We
      found 10 patients who had the BCR-ABL1 fusion gene (7%); 3 patients (2%) were
      TCF3-PBX1 positive; and 6 patients (4.5%) were ETV6-RUNX1 positive. The incidence
      of this last fusion gene is quite low when compared to the values reported in
      most countries. The low incidence of the ETV6-RUNX1 fusion gene found in
      Guatemala matches the incidence rates that have been reported in Spain and Indian
      Romani. Since it is known that an ethnic resemblance exists among these three
      populations, as shown by ancestral marker studies, the ALL data suggests an
      ethnic influence on the occurrence and frequency of this particular fusion gene. 

PMID- 23859905
TI  - Urethral lymphogranuloma venereum infections in men with anorectal
      lymphogranuloma venereum and their partners: the missing link in the current
      epidemic?
AB  - Urethral lymphogranuloma venereum (LGV) is not screened routinely. We found that
      in 341 men having sex with men with anorectal LGV, 7 (2.1%) had concurrent
      urethral LGV. Among 59 partners, 4 (6.8%) had urethral LGV infections. Urethral
      LGV is common, probably key in transmission, and missed in current routine LGV
      screening algorithms. 

PMID- 23859906
TI  - Lymphogranuloma venereum in men who have sex in men: are we missing a reservoir
      of infection?

PMID- 23859907
TI  - Prevalence, clearance, and incidence of human papillomavirus type-specific
      infection at the anal and penile site of HIV-infected men.
AB  - BACKGROUND: We studied the type-specific infection of human papillomavirus (HPV)
      at the anal canal and penile site in a cohort of HIV-infected men. METHODS:
      Prevalence, clearance, and incidence of specific HPV types in the anal canal and
      penis were determined in 733 HIV-infected men from the Spanish CAn Ruti HIV+ Men
      ([CARH*MEN]) cohort (538 men who have sex with men [MSM] and 195 heterosexual
      men). RESULTS: In both groups, the most prevalent high-risk type was HPV-16 (anal
      canal [31.6% MSM; 6.8% heterosexual] and penis [4.8% MSM; 6.8% heterosexual]).
      The most prevalent low-risk type was HPV-6 (anal canal [23.2% MSM; 12.8%
      heterosexual], penis [8.1% MSM; 8.9% heterosexual]). Anal prevalence was
      significantly higher in MSM, as was incidence, except for HPV-16, which was
      similar between male groups (5.9 new cases per 1000 person-months [95% confidence
      interval, 4.3-7.9] in MSM; 4.4 [95% confidence interval, 2.5-7.2] in heterosexual
      men; P > 0.05). The anal clearance rate of the different HPV types and retention
      time of infection were similar in both groups, as well as the HPV infection of
      the penis. CONCLUSIONS: HIV-infected MSM had a high prevalence of HPV infection
      at the anal canal; however, heterosexual HIV-infected men were also at risk for
      acquiring and sustaining persistent high-risk HPV types at the anal and penile
      site and are at risk for developing dysplasia in the future. All HIV-infected men
      should be recommended for routinely anal HPV screening.

PMID- 23859908
TI  - Analysis of HIV testing acceptance and risk factors of an adolescent cohort using
      emergency department-based multimedia HIV testing and counseling.
AB  - BACKGROUND: The social environment in the Bronx, NY, has led to HIV infection
      rates among young people that are much higher than the national average. METHODS:
      A prospective observational study on a convenience sample of medically stable
      emergency department (ED) patients was conducted from October 1, 2005, to August
      31, 2012. Acceptability of the tested model was determined by assessing the
      number of patients tested and identified HIV infections. Data were compared with
      data from the rest of the ED that tested for HIV. RESULTS: A total of 10,149
      adolescents were approached during this period, of which 9.5% refused or were
      ineligible to test. Of those approached, 38.9% of patients were male, 59.7% were
      Hispanic, and 33.6% were black. The mean age was 19.4 +/- 1.4 years, and 8.2% of
      patients were men who have sex with men. For risk behavior profiles, 24.3% never
      used condoms in the past 3 months. Incidence of HIV was less than 1%, and 92.6%
      of HIV-positive patients were linked to care. Of the patients who completed a
      postsatisfaction survey, 82.4% felt influenced to change their sexual practices.
      A smaller percentage of adolescent had tested previously for HIV compared with
      nonadolescents (67.7% vs. 80.6%). There was a slightly larger percentage of
      adolescents that accepted HIV testing compared with nonadolescents (95.4% vs.
      90.8%). Adolescents who were positive for HIV were tested earlier in the
      progression of the disease, with higher median CD4 cell counts and lower viral
      loads compared with nonadolescents. CONCLUSIONS: Adolescents were highly
      receptive to a multimedia-integrated ED-based HIV testing program, as indicated
      by their high uptake of testing.

PMID- 23859909
TI  - Methamphetamine use among women attending sexually transmitted disease clinics in
      Los Angeles County.
AB  - BACKGROUND: Methamphetamine (meth) use is a continuing problem in the United
      States and is associated with increased risk of HIV and sexually transmitted
      infections (STIs). However, few studies have examined the meth use/STI risk
      association among women. METHODS: We conducted a cross-sectional study of women
      attending public sexually transmitted disease clinics in Los Angeles County,
      California, from 2009 to 2010. Routinely collected clinic intake data were used
      to compare the prevalence of meth use among women with different
      demographics/sexual behaviors. Multivariable logistic regression was used to
      identify predictors of meth use. RESULTS: There were 1.4% (n = 277) women who
      reported meth use, with a mean age of 29 years. Prevalence was highest among
      Whites and those reporting both male and female partners. Most women who reported
      meth use also reported polysubstance use. In a multivariable model controlling
      for age, race/ethnicity, condom use, having a new sex partner, and other illicit
      substance use, women who reported sex with an injection drug user were nearly 10
      times more likely to report meth use as compared with those who did not (adjusted
      odds ratio [AOR], 9.90; 95% confidence interval [CI], 5.86-16.75). Other factors
      associated with meth use included sex with a recently incarcerated partner (AOR,
      3.24; 95% CI, 2.16-4.86), anonymous partner (AOR, 2.49; 95% CI, 1.54-4.04), and
      transactional sex (AOR, 3.26; 95% CI, 1.69-6.32). Women who tested positive for
      chlamydia/gonorrhea were 1.48 times more likely to use meth as compared with
      those who did not. CONCLUSIONS: Female meth users have high-risk behaviors that
      could increase their risk for STIs/HIV.

PMID- 23859910
TI  - Low prevalence of ciprofloxacin-resistant Neisseria gonorrhoeae in Nuuk,
      Greenland.
AB  - During a 35-day period, 32 isolates of Neisseria gonorrhoeae strains were
      collected by culture from patients with positive nucleic acid amplification test
      results in Nuuk, Greenland, where ciprofloxacin is the preferred treatment. All
      isolates were quinolone susceptible, suggesting that resistance is rare. Sampling
      patients for culture before treatment may prove useful in reestablishing
      surveillance. 

PMID- 23859911
TI  - Molecular subtyping of Treponema pallidum in Paris, France.
AB  - Two major Treponema pallidum subtypes, 14 d/g and 14 d/f, were identified in a
      population of 119 patients with syphilis in Paris, France, characterized by a
      high proportion of men who have sex with men. A new subtype named 11 q/j was
      characterized, and a reinfection case was determined in 1 patient having
      consecuitve syphilis infection at 19-month interval. 

PMID- 23859912
TI  - Polyostotic osteitis in secondary syphilis in an HIV-infected patient.
AB  - We herein describe a case of secondary syphilis in a patient with HIV infection
      that presented with an unusually diffuse polyostotic osteitis with skull
      involvement. Syphilis has to be added to the differential diagnosis of extensive
      inflammatory bone pain in patients at risk, especially if pain worsens at night. 

PMID- 23859913
TI  - High-resolution typing reveals distinct Chlamydia trachomatis strains in an at
      risk population in Nanjing, China.
AB  - We investigated Chlamydia trachomatis strains from Nanjing, China, and whether
      these strains differed from Amsterdam, the Netherlands. C. trachomatis type was
      determined with multilocus sequence typing. Most strains were specific to
      Nanjing, but some clustered with strains from Amsterdam. This demonstrates a
      geographical variation in C. trachomatis previously left undetected. 

PMID- 23859914
TI  - Thirty-two-year-old man with osteolytic skull lesion.

PMID- 23859915
TI  - Prevalence of Mycoplasma genitalium among HIV-infected women, Agence Nationale de
      Recherches sur le SIDA et les hepatites virales CO3 Aquitaine Cohort, France.

PMID- 23859916
TI  - Structural interventions for sexually transmitted infection prevention and sexual
      health.

PMID- 23859917
TI  - The legal aspects of expedited partner therapy practice: do state laws and
      policies really matter?
AB  - BACKGROUND: Expedited partner therapy (EPT) is a potential partner treatment
      strategy. Significant efforts have been devoted to policies intended to
      facilitate its practice. However, few studies have attempted to evaluate these
      policies. METHODS: We used data on interviewed gonorrhea cases from 12 sites in
      the STD Surveillance Network in 2010 (n = 3404). Patients reported whether they
      had received EPT. We coded state laws relevant to EPT for gonorrhea using Westlaw
      legal research database and the general legal status of EPT in STD Surveillance
      Network sites from Centers for Disease Control and Prevention's Web site in 2010.
      We also coded policy statements by medical and other boards. We used chi tests to
      compare receipt of EPT by legal/policy variables, patient characteristics, and
      provider type. Variables significant at P < 0.10 in bivariate analyses were
      included in a logistic regression model. RESULTS: Overall, 9.5% of 2564
      interviewed patients with gonorrhea reported receiving EPT for their partners.
      Receipt of EPT was significantly higher where laws and policies authorizing EPT
      existed. Where EPT laws for gonorrhea existed and EPT was permissible, 13.3% of
      patients reported receiving EPT as compared with 5.4% where there were no EPT
      laws and EPT was permissible, and 1.0% where there were no EPT laws and EPT was
      potentially allowable (P < 0.01). Expedited partner therapy was higher where
      professional boards had policy statements supporting EPT (P < 0.01). Receipt of
      EPT did not differ by most patient characteristics or provider type. Policy
      related findings were similar in adjusted analyses. CONCLUSIONS: Expedited
      partner therapy laws and policies were associated with higher reports of receipt
      of EPT among interviewed gonorrhea cases.

PMID- 23859919
TI  - Program collaboration and service integration: implementation successes and
      challenges.

PMID- 23859918
TI  - Enhancing HIV/AIDS, viral hepatitis, sexually transmitted disease, and
      tuberculosis prevention in the United States through program collaboration and
      service integration: the case for broader implementation.
AB  - HIV infection, viral hepatitis, sexually transmitted diseases, and tuberculosis
      in the United States remain major public health concerns. The current disease
      specific prevention approach oftentimes has led to narrow success and missed
      opportunities for increasing program capacity, leveraging resources, addressing
      social and structural determinants, and accelerating health impact-suggesting a
      need for greater innovation to prevent related diseases. The National Center for
      HIV/AIDS, Viral Hepatitis, STD, and TB Prevention's Program Collaboration and
      Service Integration (PCSI) strategic priority aims to strengthen collaborative
      engagement across these disease areas and to integrate services at the client
      level. In this review, we articulate the 5 principles of PCSI-appropriateness,
      effectiveness, flexibility, accountability, and acceptability. Drawing upon these
      principles and published literature, we discuss the case for change that
      underlies PCSI, summarize advances in the field since 2007, and articulate key
      next steps. Although formal evaluation is needed to fully assess the health
      impact of PCSI, available evidence suggests that this approach is a promising
      tool to advance prevention goals. 

PMID- 23859920
TI  - A very low potential electrochemical detection of L-cysteine based on a glassy
      carbon electrode modified with multi-walled carbon nanotubes/gold nanorods.
AB  - A nanohybrid platform built with multi-walled carbon nanotubes and gold nanorods,
      prepared via a cationic surfactant-containing seed-mediated sequential growth
      process, in aqueous solution, on a glassy carbon substrate has been successfully
      developed to be used in the electrocatalytic oxidation of L-cysteine (Cys). The
      nanohybrid was characterized by transmission electron microscopy, Raman
      spectroscopy and electrochemical measurements. Cyclic voltammetry results had
      shown that the modified electrode allows the oxidation of Cys at a very low
      anodic potential (0.00 V vs. Ag/AgCl). The kinetic constant kcat for the
      catalytic oxidation of Cys was evaluated by chronoamperometry and provided a
      value of 5.6*10(4) L mol(-1) s(-1). The sensor presents a linear response range
      from 5.0 up to 200.0 umol L(-1), detection limit of 8.25 nmol L(-1) and a
      sensitivity of 120 nA L umol(-1).

PMID- 23859921
TI  - Conformational switch for cisplatin with hemin/G-quadruplex DNAzyme supersandwich
      structure.
AB  - Cisplatin is a representative of cytotoxic and antineoplastic metallodrugs used
      for the treatment of various malignancies. In this paper, an enzyme-free
      amplification platform involving an autonomous target triggered process that
      yields the formation of the hemin/G-quadruplex DNAzyme wires was designed for the
      detection of cisplatin. Given the virtue of hemin/G-quadruplex DNAzyme wires
      (supersandwich DNAzyme structure) containing many units of hemin/G-quadruplex
      DNAzyme, an amplified electrochemical signal was achieved. Based on the
      combination of cisplatin with the guanine of the designed hemin/G-quadruplex
      DNAzyme supersandwich DNA structure, changing this structure and decreasing its
      catalytic effect on H2O2, it was used for the study on the analysis of cisplatin.
      With the concentration of the cisplatin increasing, the conformational change of
      the supersandwich DNA structure changed gradually. Then a relationship between
      the concentration of the cisplatin and the obtained electrochemical signal can be
      established. The detection concentration range of cisplatin was from 0.05 to 5
      MUM with a low detection limit of 20 nM using a signal three-fold the background
      noise and the correlation coefficient is 0.9993. The proposed approach is able to
      provide unique opportunities as simplicity in design and easy operations.
      Therefore, the proposed sensor presents remarkably high sensitivity and
      selectivity.

PMID- 23859922
TI  - Depth-compensated diffuse optical tomography enhanced by general linear model
      analysis and an anatomical atlas of human head.
AB  - One of the main challenges in functional diffuse optical tomography (DOT) is to
      accurately recover the depth of brain activation, which is even more essential
      when differentiating true brain signals from task-evoked artifacts in the scalp.
      Recently, we developed a depth-compensated algorithm (DCA) to minimize the depth
      localization error in DOT. However, the semi-infinite model that was used in DCA
      deviated significantly from the realistic human head anatomy. In the present
      work, we incorporated depth-compensated DOT (DC-DOT) with a standard anatomical
      atlas of human head. Computer simulations and human measurements of sensorimotor
      activation were conducted to examine and prove the depth specificity and
      quantification accuracy of brain atlas-based DC-DOT. In addition, node-wise
      statistical analysis based on the general linear model (GLM) was also implemented
      and performed in this study, showing the robustness of DC-DOT that can accurately
      identify brain activation at the correct depth for functional brain imaging, even
      when co-existing with superficial artifacts. 

PMID- 23859923
TI  - The current state-of-the-art of spinal cord imaging: applications.
AB  - A first-ever spinal cord imaging meeting was sponsored by the International
      Spinal Research Trust and the Wings for Life Foundation with the aim of
      identifying the current state-of-the-art of spinal cord imaging, the current
      greatest challenges, and greatest needs for future development. This meeting was
      attended by a small group of invited experts spanning all aspects of spinal cord
      imaging from basic research to clinical practice. The greatest current challenges
      for spinal cord imaging were identified as arising from the imaging environment
      itself; difficult imaging environment created by the bone surrounding the spinal
      canal, physiological motion of the cord and adjacent tissues, and small
      crosssectional dimensions of the spinal cord, exacerbated by metallic implants
      often present in injured patients. Challenges were also identified as a result of
      a lack of "critical mass" of researchers taking on the development of spinal cord
      imaging, affecting both the rate of progress in the field, and the demand for
      equipment and software to manufacturers to produce the necessary tools. Here we
      define the current state-of-the-art of spinal cord imaging, discuss the
      underlying theory and challenges, and present the evidence for the current and
      potential power of these methods. In two review papers (part I and part II), we
      propose that the challenges can be overcome with advances in methods, improving
      availability and effectiveness of methods, and linking existing researchers to
      create the necessary scientific and clinical network to advance the rate of
      progress and impact of the research. 

PMID- 23859924
TI  - Single-trial decoding of auditory novelty responses facilitates the detection of
      residual consciousness.
AB  - Detecting residual consciousness in unresponsive patients is a major clinical
      concern and a challenge for theoretical neuroscience. To tackle this issue, we
      recently designed a paradigm that dissociates two electro-encephalographic (EEG)
      responses to auditory novelty. Whereas a local change in pitch automatically
      elicits a mismatch negativity (MMN), a change in global sound sequence leads to a
      late P300b response. The latter component is thought to be present only when
      subjects consciously perceive the global novelty. Unfortunately, it can be
      difficult to detect because individual variability is high, especially in
      clinical recordings. Here, we show that multivariate pattern classifiers can
      extract subject-specific EEG patterns and predict single-trial local or global
      novelty responses. We first validate our method with 38 high-density EEG, MEG and
      intracranial EEG recordings. We empirically demonstrate that our approach
      circumvents the issues associated with multiple comparisons and individual
      variability while improving the statistics. Moreover, we confirm in control
      subjects that local responses are robust to distraction whereas global responses
      depend on attention. We then investigate 104 vegetative state (VS), minimally
      conscious state (MCS) and conscious state (CS) patients recorded with high
      density EEG. For the local response, the proportion of significant decoding
      scores (M=60%) does not vary with the state of consciousness. By contrast, for
      the global response, only 14% of the VS patients' EEG recordings presented a
      significant effect, compared to 31% in MCS patients' and 52% in CS patients'. In
      conclusion, single-trial multivariate decoding of novelty responses provides
      valuable information in non-communicating patients and paves the way towards real
      time monitoring of the state of consciousness. 

PMID- 23859925
TI  - Simultaneous quantitative assessment of cerebral physiology using respiratory
      calibrated MRI and near-infrared spectroscopy in healthy adults.
AB  - BACKGROUND: Functional near-infrared spectroscopy (fNIRS) and functional MRI
      (fMRI) are non-invasive techniques used to relate activity in different brain
      regions to certain tasks. Respiratory calibration of the blood oxygen level
      dependent (BOLD) signal, and combined fNIRS-fMRI approaches have been used to
      quantify physiological subcomponents giving rise to the BOLD signal. A comparison
      of absolute oxygen metabolism parameters between MRI and NIRS, using spatially
      resolved (SRS) NIRS and respiratory calibrated MRI, could yield additional
      insight in the physiology underlying activation. MATERIALS AND METHODS: Changes
      in the BOLD signal, cerebral blood flow (CBF), and oxygen saturation (SO2) were
      derived from a single MRI sequence during a respiratory challenge in healthy
      volunteers. These changes were compared to SO2 obtained by a single probe SRS
      NIRS setup. In addition, concentration changes in oxygenated (O2Hb), deoxygenated
      (HHb), and total haemoglobin (tHb), obtained by NIRS, were compared to the
      parameters obtained by MRI. RESULTS: NIRS SO2 correlated with end-tidal CO2
      (0.83, p<0.0001), the BOLD signal (0.82, p<0.0001), CBF (0.85, p<0.0001), and
      also MRI SO2 (0.82, p<0.0001). The BOLD signal correlated with NIRS HHb (-0.76,
      p<0.0001), O2Hb (0.41, p=0.001), and tHb (r=0.32, p=0.01). CONCLUSIONS: Good
      correlations show that changes in cerebral physiology, following a respiratory
      challenge, go hand in hand with changes in the BOLD signal, CBF, O2Hb, HHb, NIRS
      SO2, and MRI SO2. Out of all NIRS derived parameters, the SO2 showed the best
      correlation with the BOLD signal.

PMID- 23859926
TI  - A traffic light food labeling intervention increases consumer awareness of health
      and healthy choices at the point-of-purchase.
AB  - OBJECTIVE: We surveyed customers in a hospital cafeteria in Boston, Massachusetts
      before and after implementation of traffic light food labeling to determine the
      effect of labels on customers' awareness and purchase of healthy foods. METHODS:
      Cafeteria items were identified as red (unhealthy), yellow (less healthy), or
      green (healthy). Customers were interviewed before (N=166) and after (N=223)
      labeling was implemented. Each respondent was linked to cash register data to
      determine the proportion of red, yellow, and green items purchased. Data were
      collected from February-April 2010. We compared responses to survey questions and
      mean proportion of red, yellow, and green items per transaction between customers
      interviewed during baseline and customers interviewed during the intervention.
      Survey response rate was 60%. RESULTS: Comparing responses during labeling
      intervention to baseline, more respondents identified health/nutrition as an
      important factor in their purchase (61% vs. 46%, p=0.004) and reported looking at
      nutrition information (33% vs. 15%, p<0.001). Respondents who noticed labels
      during the intervention and reported that labels influenced their purchases were
      more likely to purchase healthier items than respondents who did not notice
      labels (p<0.001 for both). CONCLUSION: Traffic light food labels prompted
      individuals to consider their health and to make healthier choices at point-of
      purchase.

PMID- 23859927
TI  - Receipt of human papillomavirus vaccine among privately insured adult women in a
      U.S. Midwestern Health Maintenance Organization.
AB  - OBJECTIVES: To describe human papillomavirus (HPV) vaccine coverage among adult
      privately insured women including variation in coverage by race/ethnicity.
      METHODS: This cross-sectional, observational study included women 18-26 years of
      age with continuous enrollment in a U.S. Midwestern health insurance plan and at
      least one visit to a plan affiliated practice. Vaccination data came from
      insurance claims and the electronic medical record. Primary outcomes were:
      receipt of at least 1 HPV vaccine (HPV1) and completion of the 3-dose HPV vaccine
      series (HPV3). Coverage was described for the entire cohort and stratified by
      race/ethnicity. For a subset of women, automated data was compared to personal
      recall. RESULTS: As of June 2010, among 2546 privately insured women 18-26 years,
      72.7% had received their first HPV vaccine and 57.9% completed the 3-dose series.
      Compared to white women, African American and Asian women had significantly lower
      coverage for HPV1 and HPV3. There was 94.5% (95% CI: 88.5-100%) agreement between
      personal recall and claims/EMR for receiving HPV1. CONCLUSIONS: In this cohort of
      privately insured women, a majority received HPV1 and more than half completed
      the 3-dose vaccine series. Marked disparities in receipt of HPV vaccine by
      race/ethnicity were observed.

PMID- 23859930
TI  - A spatial analysis of the association between restaurant density and body mass
      index in Canadian adults.
AB  - OBJECTIVE: To investigate the association between fast-food restaurant density
      and adult body mass index (BMI) in Canada. METHODS: Individual-level BMI and
      confounding variables were obtained from the 2007-2008 Canadian Community Health
      Survey master file. Locations of the fast-food and full-service chain restaurants
      and other non-chain restaurants were obtained from the 2008 Infogroup Canada
      business database. Food outlet density (fast-food, full-service and other) per
      10,000 population was calculated for each Forward Sortation Area (FSA). Global
      (Moran's I) and local indicators of spatial autocorrelation of BMI were assessed.
      Ordinary least squares (OLS) and spatial auto-regressive error (SARE) methods
      were used to assess the association between local food environment and adult BMI
      in Canada. RESULTS: Global and local spatial autocorrelation of BMI were found in
      our univariate analysis. We found that OLS and SARE estimates were very similar
      in our multivariate models. An additional fast-food restaurant per 10,000 people
      at the FSA-level is associated with a 0.022kg/m(2) increase in BMI. On the other
      hand, other restaurant density is negatively related to BMI. CONCLUSIONS: Fast
      food restaurant density is positively associated with BMI in Canada. Results
      suggest that restricting availability of fast-food in local neighborhoods may
      play a role in obesity prevention.

PMID- 23859928
TI  - Alcohol consumption and risk of stroke and coronary heart disease among Japanese
      women: the Japan Public Health Center-based prospective study.
AB  - OBJECTIVE: The study aims to examine the association between a wide range of
      alcohol consumption and risk of stroke and coronary heart disease. METHODS: The
      Japan Public Health Center-based prospective study was initiated in 1990 in
      Cohort I and in 1993 in Cohort II, with follow-up until 2009. The sample
      consisted of 47,100 women aged 40-69 years. RESULTS: During an average of 16.7
      years, the incidence of 1846 strokes and 292 coronary heart diseases was
      observed. Heavy drinking (>= 300 gethanol/week) was associated with increased
      risk of total stroke. The multivariable hazard ratios for heavy versus occasional
      drinkers were 2.19 (95% confidence interval: 1.45-3.30) for total stroke, 2.25
      (1.29-3.91) for hemorrhagic stroke, 2.24 (1.05-4.76) for intraparenchymal
      hemorrhage, 2.26 (1.01-5.09) for subarachnoid hemorrhage and 2.04 (1.09-3.82) for
      ischemic stroke. In the exposure-updated analysis, the positive association
      between heavy drinking and risks of total stroke, hemorrhagic stroke and
      intraparenchymal hemorrhage became more evident. Light drinking (<150
      gethanol/week) was not associated with risk of ischemic stroke. There was also no
      association between alcohol consumption and risk of coronary heart disease.
      CONCLUSION: Heavy drinking was associated with increased risk of hemorrhagic and
      ischemic strokes among Japanese women.

PMID- 23859929
TI  - Weight and metabolic effects of dietary weight loss and exercise interventions in
      postmenopausal antidepressant medication users and non-users: a randomized
      controlled trial.
AB  - OBJECTIVE: Antidepressants may attenuate the effects of diet and exercise
      programs. We compared adherence and changes in body measures and biomarkers of
      glucose metabolism and inflammation between antidepressant users and non-users in
      a 12-month randomized controlled trial. METHODS: Overweight or obese,
      postmenopausal women were assigned to: diet (10% weight loss goal, N=118);
      moderate-to-vigorous aerobic exercise (225 min/week, N=117); diet+exercise
      (N=117); and control (N=87) in Seattle, WA 2005-2009. Women using antidepressants
      at baseline were classified as users (N=109). ANCOVA and generalized estimating
      equation approaches, respectively, were used to compare adherence (exercise
      amount, diet session attendance, and changes in percent calorie intake from fat,
      cardiopulmonary fitness, and pedometer steps) and changes in body measures
      (weight, waist and percent body fat) and serum biomarkers (glucose, insulin,
      homeostasis assessment-insulin resistance, and high-sensitivity C-reactive
      protein) between users and non-users. An interaction term
      (intervention*antidepressant use) tested effect modification. RESULTS: There were
      no differences in adherence except that diet session attendance was lower among
      users in the diet+exercise group (P<0.05 vs. non-users). Changes in body measures
      and serum biomarkers did not differ by antidepressant use (Pinteraction>0.05).
      CONCLUSION: Dietary weight loss and exercise improved body measures and
      biomarkers of glucose metabolism and inflammation independent of antidepressant
      use.

PMID- 23859931
TI  - Crime, physical activity and outdoor recreation among Latino adolescents in
      Chicago.
AB  - PURPOSE: The purpose was to examine how fear of crime, crime victimization, and
      perceived level of community incivilities are related to physical activity
      participation and outdoor recreation among Latino adolescents. METHOD: The study
      utilized a mixed methods approach that included 25 qualitative interviews and 390
      school-based surveys collected from youth across three schools in Little Village,
      Chicago, Illinois. RESULTS: Results showed that Latino adolescents who expressed
      greater fear of crime also engaged in less physical activity and outdoor
      recreation. There was no association between crime victimization and physical
      activity and outdoor recreation. Those who perceived greater levels of community
      incivilities also engaged in less outdoor recreation, but perception of
      incivilities had no significant association with physical activity levels.
      Interview data revealed most of the children believed crime was a serious problem
      in their neighborhood and it impacted their ability to be physically active and
      play outside. CONCLUSIONS: Fear of crime was related to lower physical activity
      and outdoor recreation. It is imperative that communities provide safe
      environments for children to be active. Increasing police and adult presence in
      parks and school grounds is recommended. Moreover, efforts must be made to reduce
      the gang problems in Latino communities.

PMID- 23859933
TI  - Who uses new walking and cycling infrastructure and how? Longitudinal results
      from the UK iConnect study.
AB  - OBJECTIVE: To examine how adults use new local walking and cycling routes, and
      what characteristics predict use. METHODS: 1849 adults completed questionnaires
      in 2010 and 2011, before and after the construction of walking and cycling
      infrastructure in three UK municipalities. 1510 adults completed questionnaires
      in 2010 and 2012. The 2010 questionnaire measured baseline characteristics; the
      follow-up questionnaires captured infrastructure use. RESULTS: 32% of
      participants reported using the new infrastructure in 2011, and 38% in 2012.
      Walking for recreation was by far the most common use. In both follow-up waves,
      use was independently predicted by higher baseline walking and cycling (e.g. 2012
      adjusted rate ratio 2.09 (95% CI 1.55, 2.81) for >450 min/week vs. none).
      Moreover, there was strong specificity by mode and purpose, e.g. baseline walking
      for recreation specifically predicted walking for recreation on the
      infrastructure. Other independent predictors included living near the
      infrastructure, better general health and higher education or income.
      CONCLUSIONS: The new infrastructure was well-used by local adults, and this was
      sustained over two years. Thus far, however, the infrastructure may primarily
      have attracted existing walkers and cyclists, and may have catered more to the
      socio-economically advantaged. This may limit its impacts on population health
      and health equity.

PMID- 23859932
TI  - Mapping the development of research on physical activity and the built
      environment.
AB  - OBJECTIVE: The importance of the built environment for physical activity has been
      recognized in recent decades, resulting in new research. This study aims to
      understand the current structure of physical activity and built environment
      (PABE) research and identify gaps to address as the field continues to rapidly
      develop. METHODS: Key PABE articles were nominated by top scholars and a snowball
      sample of 2764 articles was collected in 2013 using citation network links.
      Article abstracts were examined to determine research focus and network analysis
      was used to examine the evolution of scholarship. RESULTS: The network included
      318 PABE articles. Of these, 191 were discovery-focused, examining the
      relationship between physical activity and built environment; 79 were reviews
      summarizing previous PABE work; 38 focused on theory and methods for studying
      PABE; six were delivery-focused, examining PABE interventions; and four addressed
      other topics. CONCLUSIONS: Network composition suggested that PABE is in the
      discovery phase, although may be transitioning given the large number and central
      position of review documents that summarize existing literature. The small amount
      of delivery research was not well integrated into the field. PABE delivery
      researchers may wish to make explicit connections to the discovery literature in
      order to better integrate the field.

PMID- 23859934
TI  - Effects of a physical activity and healthy eating intervention to reduce stroke
      risk factors in older adults.
AB  - OBJECTIVE: To evaluate the effects of a theory-based physical activity and
      healthy eating intervention aimed at reducing stroke risk factors among
      overweight/obese and sedentary older adults. METHODS: Between 12/2009-1/2011,
      participants (n=69) were randomly assigned to an 8-week group motivational
      intervention or biweekly newsletters by mail. Physical activity (blinded
      pedometer, 7-day recall) body composition, theoretical mediator, and dietary (24
      hour recall) variables were measured at pre-test and post-test. The physical
      activity and dietary outcomes are reported. RESULTS: For outcome measures, the
      follow-up was 90% for the intervention group (n=29) and 91% for the control group
      (n=34) for this sample. Statistically significant differences in the 7-day
      physical activity self-report were noted at post-test in the intervention group.
      The dietary measures were not statistically significant at post-test; however,
      the intervention group increased the quantity of vegetable servings. CONCLUSION:
      Limited efficacy testing was supported for a combined physical activity-dietary
      intervention, framed by a wellness-motivation theory, and designed to reduce
      stroke risk factors in older adults who are sedentary and overweight/obese.
      Limitations were identified and recommendations for additional research provided.

PMID- 23859935
TI  - Inflammatory activation after experimental cardiac tamponade.
AB  - BACKGROUND/PURPOSE: Cardiac tamponade is a medical emergency situation associated
      with a high rate of life-threatening complications, even after immediate
      interventions. Our aim was to characterize the acute inflammatory consequences of
      this event in a clinically relevant large animal model. METHODS: Cardiac
      tamponade was induced for 60 min in anesthetized, ventilated and thoracotomized
      minipigs by intrapericardial fluid administration, the mean arterial pressure
      (MAP) being maintained in the interval of 40-45 mm Hg (n = 8). A further group (n
      = 7) served as sham-operated control. The global macrohemodynamics, including the
      right- and left-heart end-diastolic volumes (RHEDV and LHEDV), the pulmonary
      vascular resistance index (PVRI) and the superior mesenteric artery (SMA) flow,
      were monitored for 240 min, and the intestinal microcirculatory changes (pCO2
      gap) were evaluated by indirect tonometry. Blood samples were taken for the
      determination of cardiac troponin T and vasoactive inflammatory mediators,
      including histamine, nitrite/nitrate, big-endothelin, superoxide and high
      mobility group box protein-1 levels in association with intestinal leukocyte and
      complement activation. RESULTS: The cardiac tamponade induced significant
      decreases in MAP, cardiac output, LHEDV and SMA flow, while the PVRI and the pCO2
      gap increased significantly. After the removal of fluid from the pericardial sac,
      the MAP and the LHEDV were decreased, while the PVRI and the pCO2 gap remained
      elevated when compared with those in the sham-operated group. In the
      posttamponade period, the abrupt release of inflammatory mediators was
      accompanied by a significant splanchnic leukocyte accumulation and complement
      activation. CONCLUSIONS: The macrocirculatory and splanchnic microcirculatory
      disturbances were accompanied by a significant proinflammatory reaction;
      endothelin and the complement system may be significant components of the
      inflammatory cascade that is activated in this porcine model of pericardial
      tamponade.

PMID- 23859936
TI  - Anterior inferior cerebellar artery territorial infarction caused by vertebral
      artery dissection.

PMID- 23859937
TI  - Anti-c-Met antibodies recognising a temperature sensitive epitope, inhibit cell
      growth.
AB  - c-Met is a tyrosine receptor kinase which is activated by its ligand, the
      hepatocyte growth factor. Activation of c-Met leads to a wide spectrum of
      biological activities such as motility, angiogenesis, morphogenesis, cell
      survival and cell regeneration. c-Met is abnormally activated in many tumour
      types. Aberrant c-Met activation was found to induce tumour development, tumour
      cell migration and invasion, and the worst and final step in cancer progression,
      metastasis. In addition, c-Met activation in cells was also shown to confer
      resistance to apoptosis induced by UV damage or chemotherapeutic drugs. This
      study describes the development of monoclonal antibodies against c-Met as
      therapeutic molecules in cancer treatment/diagnostics. A panel of c-Met
      monoclonal antibodies was developed and characterised by epitope mapping, Western
      blotting, immunoprecipitation, agonist/antagonist effect in cell scatter assays
      and for their ability to recognise native c-Met by flow cytometry. We refer to
      these antibodies as Specifically Engaging Extracellular c-Met (seeMet). seeMet 2
      and 13 bound strongly to native c-Met in flow cytometry and reduced SNU-5 cell
      growth. Interestingly, seeMet 2 binding was strongly reduced at 4oC when compared
      to 37oC. Detail mapping of the seeMet 2 epitope indicated a cryptic binding site
      hidden within the c-Met alpha-chain. 

PMID- 23859938
TI  - Cardiovascular coupling analysis with high-resolution joint symbolic dynamics in
      patients suffering from acute schizophrenia.
AB  - Besides the well-known cardiac risk factors for schizophrenia, increasing
      concerns have been raised regarding the cardiac side-effects of antipsychotic
      medications. A bivariate analysis of autonomic regulation, based on
      cardiovascular coupling, can provide additional information about heart rate (HR)
      and blood pressure regulatory patterns within the complex interactions of the
      cardiovascular system. We introduce a new high-resolution coupling analysis
      method (HRJSD) based on joint symbolic dynamics (JSD), which is characterized by
      three symbols, a threshold (individual dynamic variability, physiological) for
      time series transformation and eight coupling pattern families. This is based on
      a redundancy reduction strategy used to quantify and characterize cardiovascular
      couplings. In this study, short-term (30 min) HR and systolic blood pressure (SP)
      time series of 42 unmedicated (UNMED) and 42 medicated patients (MED) suffering
      from acute schizophrenia were analysed to establish the suitability of the new
      method for quantifying the effects of antipsychotics on cardiovascular couplings.
      We were able to demonstrate that HRJSD, applying the threshold based on
      spontaneous baroreflex sensitivity (BRS) estimation, revealed eight significant
      pattern families that were able to quantify the anti-cholinergic effects of
      antipsychotics and the related changes of cardiovascular regulation (coupling) in
      MED in comparison to UNMED. This was in contrast to the simple JSD, BRS (sequence
      method) and only partly to standard linear HR variability indices. HRJSD provides
      strong evidence that autonomic regulation in MED seems to be, to some extent,
      predominated by invariable HR responses in combination with alternating SP values
      in contrast to UNMED, indicating an impairment of the baroreflex control feedback
      loop in MED. Surrogate data analysis was applied to test for the significance and
      nonlinearity of cardiovascular couplings in the original data due to medical
      treatment with antipsychotic drugs in MED. In conclusion, the application of
      HRJSD revealed detailed information about short-term nonlinear cardiovascular
      couplings and cardiovascular physiological regulatory mechanisms (patterns) of
      autonomic function due to the anti-cholinergic effects of antipsychotics in
      patients with acute schizophrenia. 

PMID- 23859939
TI  - Permutation entropy of scalp EEG: a tool to investigate epilepsies: suggestions
      from absence epilepsies.
AB  - OBJECTIVE: We used permutation entropy (PE) to disclose abnormalities of cerebral
      activity in patients with typical absences (TAs). METHODS: We evaluated 24 EEG of
      TA patients and 40 EEG of healthy subjects. PE was estimated channel by channel,
      with electrodes being divided into high-PE cluster (high randomness), low-PE
      cluster (low randomness), and neutral cluster. We compared PE between EEG of
      patients and controls, and between interictal and ictal EEG of patients. RESULTS:
      Patients showed a recurrent behavior of PE topography, with anterior brain
      regions constantly associated to high PE levels and posterior brain regions
      constantly associated to low PE levels, during both interictal and ictal phases.
      On the contrary, healthy controls had a random distribution of PE topography.
      CONCLUSIONS: In patients with TAs, a higher randomness in fronto-temporal areas
      and a lower randomness in posterior areas occur during both interictal and ictal
      phases. Such abnormalities are in keeping with evidences from different
      morphological and functional studies showing multifocal brain changes in TA
      patients. SIGNIFICANCE: PE seems to be a useful tool to disclose abnormalities of
      cerebral electric activity not revealed by conventional EEG recordings, opening
      interesting prospective for future studies.

PMID- 23859940
TI  - Hepatic gene expression in herbivores on diets with natural and novel plant
      secondary compounds.
AB  - Herbivores are predicted to evolve appropriate mechanisms to process the plant
      secondary compounds (PSCs) in their diet, and these mechanisms are likely
      specific to particular suites of PSCs. Changes in diet composition over
      evolutionary time should select for appropriate alterations in metabolism of the
      more recent dietary components. We investigated differences in gene expression
      profiles in the liver with respect to prior ecological and evolutionary
      experience with PSCs in the desert woodrat, Neotoma lepida. This woodrat species
      has populations in the Mojave Desert that have switched from feeding on juniper
      to feeding on creosote at the end of the Holocene as well as populations in the
      Great Basin Desert that still feed on the ancestral diet of juniper and are naive
      to creosote. Juniper and creosote have notable differences in secondary
      chemistry. Woodrats from the Mojave and Great Basin Deserts were subjected to a
      fully crossed feeding trial on diets of juniper and creosote after which their
      livers were analyzed for gene expression. Hybridization of hepatic mRNAs to
      laboratory rat microarrays resulted in a total of 20,031 genes that met quality
      control standards. We analyzed differences in large-scale patterns of liver gene
      expression with respect to GO term enrichment. Diet had a larger effect on gene
      expression than population membership. However, woodrats with no prior
      evolutionary experience to the diet upregulated a greater proportion of genes
      indicative of physiological stress compared with those on their natural diet.
      This pattern may be the result of a naive animal's attempting to mitigate
      physiological damage caused by novel PSCs. 

PMID- 23859942
TI  - Evidence of elevated levels of polychlorinated biphenyl congeners in commonly
      consumed fish from Eleyele Reservoir, Southwestern Nigeria.
AB  - Environmental pollution of water, which is a source of cheap and affordable
      protein in the form of fish on which the population depends on, is of great
      concern globally. The present study assesses the levels of polychlorinated
      biphenyls (PCBs) congeners in sediments and six commonly consumed cichlid species
      from Eleyele Reservoir, Southwestern Nigeria. The results indicate that the
      concentrations of heavier PCB congeners are higher than the lighter congeners in
      both sediment and fish tissue. The predominant PCB congeners in the sediment
      samples from this site were PCBs 8, 44, 114, 101, 189, 196, 206 and 209. The
      concentration of PCB congeners increased with increasing molecular weight from
      hepta-PCB to deca-PCB in all fish species. The trend in accumulation of total
      PCBs in fish was as follows: Tilapia guineensis (2,531.1 +/- 74.6 ng/g) >
      Sarotherodon galilaeus (1178.7 +/- 68.5 ng/g) > Oreochromis niloticus > (891.8 +/
      49.6 ng/g) > Tilapia zillii (832.8 +/- 38.2 ng/g) > Hemichromis fasciatus (475.7
      +/- 28.5 ng/g) > Sarotherodon melanotheron (333.2 +/- 26.1 ng/g). In summary,
      data from this study shows that the levels of PCBs in cichlid species from
      Eleyele Reservoir are higher than the threshold level of 0.023-0.047 ng g(-1)
      recommended by United States Environmental Protection Agency. Such elevated PCB
      levels present significant health implications for human consumers and a threat
      to the resident fish communities.

PMID- 23859941
TI  - Taste dysfunction in BTBR mice due to a mutation of Itpr3, the inositol
      triphosphate receptor 3 gene.
AB  - The BTBR T+ tf/J (BTBR) mouse strain is indifferent to exemplars of sweet,
      Polycose, umami, bitter, and calcium tastes, which share in common transduction
      by G protein-coupled receptors (GPCRs). To investigate the genetic basis for this
      taste dysfunction, we screened 610 BTBR*NZW/LacJ F2 hybrids, identified a potent
      QTL on chromosome 17, and isolated this in a congenic strain. Mice carrying the
      BTBR/BTBR haplotype in the 0.8-Mb (21-gene) congenic region were indifferent to
      sweet, Polycose, umami, bitter, and calcium tastes. To assess the contribution of
      a likely causative culprit, Itpr3, the inositol triphosphate receptor 3 gene, we
      produced and tested Itpr3 knockout mice. These were also indifferent to GPCR
      mediated taste compounds. Sequencing the BTBR form of Itpr3 revealed a unique 12
      bp deletion in Exon 23 (Chr 17: 27238069; Build 37). We conclude that a
      spontaneous mutation of Itpr3 in a progenitor of the BTBR strain produced a
      heretofore unrecognized dysfunction of GPCR-mediated taste transduction.

PMID- 23859943
TI  - Sphingomicrobium marinum sp. nov. and Sphingomicrobium flavum sp. nov., isolated
      from surface seawater, and emended description of the genus Sphingomicrobium.
AB  - Two Gram-staining-negative, yellow-pigmented, rod-shaped, strictly aerobic, non
      flagellated and non-spore-forming amylolytic marine bacterial strains, designated
      CC-AMZ-30M(T) and CC-AMZ-30N(T), were isolated from coastal surface seawater in
      Taiwan. Strain CC-AMZ-30M(T) shared pairwise 16S rRNA gene sequence similarities
      of 95.8, 95.0 and <94.0 % to Sphingomicrobium lutaoense CC-TBT-3(T),
      Sphingomicrobium astaxanthinifaciens CC-AMO-30B(T) and other sphingomonads,
      respectively. Strain CC-AMZ-30N(T) shared 97.0, 96.7, 95.0 and <95.1 %
      similarities to strain CC-AMZ-30M(T), Sphingomicrobium lutaoense CC-TBT-3(T),
      Sphingomicrobium astaxanthinifaciens CC-AMO-30B(T) and other sphingomonads,
      respectively. The common polar lipids of the two strains include a signature
      glycolipid (GL2), diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and sphingoglycolipid in major amounts besides moderate
      to-trace amounts of an unidentified aminolipid and several unidentified
      glycolipids. Both strains contained C18 : 1omega7c/C18 : 1omega6c, C16 :
      1omega7c/C16 : 1omega6c, C16 : 0 and C18 : 1 2-OH as major (>5 % of the total)
      fatty acids. Strains CC-AMZ-30M(T) and CC-AMZ-30N(T) had DNA G+C contents of 64.2
      and 65.2 mol%, respectively. The major polyamine was spermidine in strain CC-AMZ
      30M(T) and triamine sym-homospermidine in strain CC-AMZ-30N(T). Both strains
      contained ubiquinone Q-10 as the predominant respiratory quinone. Differential
      phylogenetic and chemotaxonomic evidence including the presence of characteristic
      GL2, C18 : 1 2-OH and several other phenotypic features supported the
      classification of strains CC-AMZ-30M(T) and CC-AMZ-30N(T) as two novel species of
      the genus Sphingomicrobium, for which we propose the names Sphingomicrobium
      marinum sp. nov. and Sphingomicrobium flavum sp. nov., respectively;
      corresponding type strains are Sphingomicrobium marinum CC-AMZ-30M(T) ( = JCM
      18554(T) = BCRC 80466(T)) and Sphingomicrobium flavum CC-AMZ-30N(T) ( = JCM
      18555(T) = BCRC 80467(T)). An emended description of the genus Sphingomicrobium
      is also proposed. 

PMID- 23859944
TI  - Sphingobacterium changzhouense sp. nov., a bacterium isolated from a rice field.
AB  - A Gram-stain-negative, yellow, non-spore-forming, rod-shaped bacterium,
      designated N7(T), was isolated from a soil sample collected from a rice field in
      Jiangsu, China, and was characterized using a polyphasic taxonomic approach.
      Strain N7(T) grew optimally at 25-30  degrees C, pH 6.0-8.0, and in the presence
      of 1 % NaCl (w/v). 16S rRNA gene sequence analysis indicated that strain N7(T)
      was a member of the genus Sphingobacterium and was closely related to
      Sphingobacterium multivorum IAM14316(T) (97.49 %) and Sphingobacterium canadense
      CR11(T) (97.11 %), sharing less than 97 % sequence similarities with other
      species of the genus Sphingobacterium. The predominant respiratory quinone of
      strain N7(T) was MK-7 and major fatty acids were summed features 3 (C16 :
      1omega6c and/or C16 : 1omega7c), iso-C15 : 0, C16 : 0 and iso-C17 : 0 3-OH. The
      G+C content of the DNA was 40.9+/-0.5 mol%. The levels of DNA-DNA relatedness
      between strain N7(T) and the most closely related species S. multivorum IAM
      14316(T) and S. canadense CR11(T) were 21 % and 15 %, respectively. Based on
      these results, strain N7(T) is proposed to represent a separate species within
      the genus Sphingobacterium. The name Sphingobacterium changzhouense sp. nov. is
      suggested and the type strain is N7(T) ( = CCTCC AB 2012100(T) = KACC 16854(T)). 

PMID- 23859945
TI  - Lacibacter daechungensis sp. nov., isolated from deep freshwater of a reservoir.
AB  - A Gram-stain-negative, aerobic, motile by gliding, non-spore-forming, rod-shaped,
      orange-pigmented bacterium, designated strain H32-4(T), was isolated from 32 m
      deep water of Daechung reservoir in Daejeon, Republic of Korea. Based on the
      nucleotide sequence of the 16S rRNA gene, the closest neighbouring type strain
      was Lacibacter cauensis NJ-8(T) with which strain H32-4(T) shared 98.9% sequence
      similarity. The most abundant fatty acids in whole cells of strain H32-4(T) were
      C15 : 0 iso (40.6 %), C17 : 0 iso 3-OH (22.4%), summed feature 3 (C16:1omega7c
      and/or C16:1omega6c; 9.3%) and C15:0 (6.6 %). The predominant menaquinone was MK
      7. The G+C content of the genomic DNA of strain H32-4(T) was 45.7 mol%. Thus,
      these combined genotypic and phenotypic data supported the conclusion that strain
      H32-4(T) represents a novel species of the genus Lacibacter, for which the name
      Lacibacter daechungensis sp. nov. is proposed. The type strain is H32-4(T) ( =
      KCTC 32395(T) = JCM 19172(T)).

PMID- 23859946
TI  - Natranaerobaculum magadiense gen. nov., sp. nov., an anaerobic,
      alkalithermophilic bacterium from soda lake sediment.
AB  - An obligately alkaliphilic, anaerobic, thermo- and halotolerant, spore-forming
      bacterium was isolated from sediments of soda lake Magadi (Kenya) and designated
      strain Z-1001(T). Cells of strain Z-1001(T) were straight, Gram-positive rods,
      slowly motile. Strain Z-1001(T) was found to be an obligate anaerobe. It grew
      within a pH range from 7.5 to 10.7 with an optimum at 9.25-9.5 (at 40  degrees
      C), a temperature range from 20 to 57  degrees C with an optimum at 45-50 
      degrees C, and a NaCl concentration range from 0 to 1.55 M with an optimum at 1.2
      1.4 M. Peptides, such as meat and yeast extracts, peptone and tryptone, were
      fermented by Z-1001(T). Carbohydrates did not support growth. With yeast extract
      as an electron donor, strain Z-1001(T) reduced S(2)O(3)(2-), NO(-)(3), AsO(3
      )(4), Fe(III) citrate and anthraquinone-2,6-disulfonate (AQDS) as electron
      acceptors. The isolate was able to grow oligotrophically with a very small amount
      of yeast extract: 0.03 g l(-1). The main fatty acids were C16 : 0, C16 :
      1omega7c, C18 : 0 and C18 : 1omega9. The DNA G+C content of the isolate was 35.6
      mol%. 16S rRNA gene sequence analysis showed that strain Z-1001(T) is a member of
      family Natranaerobiaceae, clustering with the type strain of Natranaerobius
      thermophilus (95.8-96.0 % sequence similarity). On the basis of physiological and
      phylogenetic data it is proposed that strain Z-1001(T) ( = DSM 24923(T) = VKM B
      2666(T)) represents a novel genus and species, Natranaerobaculum magadiense gen.
      nov., sp. nov.

PMID- 23859947
TI  - Morphology and small-subunit rRNA gene sequences of two novel marine ciliates,
      Metanophrys orientalis spec. nov. and Uronemella sinensis spec. nov. (Protista,
      Ciliophora, Scuticociliatia), with an improved diagnosis of the genus Uronemella.
AB  - The morphology and infraciliature of two novel marine scuticociliates,
      Metanophrys orientalis spec. nov. and Uronemella sinensis spec. nov., collected
      from sandy beaches at Qingdao, China, were investigated using live observation
      and protargol-staining methods. Metanophrys orientalis spec. nov. is
      distinguished by the following characteristics: marine habitat and a slender to
      elongate oval body with pointed anterior end and rounded caudal end, in vivo
      about 25-50 um long; buccal field about a quarter to a third of body length; nine
      or ten somatic kineties with dikinetids approximately in anterior half of body,
      monokinetids in posterior half; membranelles 1 and 2 almost equal in length and
      composed of two and three longitudinal rows of kinetids respectively; paroral
      membrane with zigzag structure extending anteriorly to middle portion of
      membranelle 2; contractile vacuole pore located at posterior end of somatic
      kinety 1. The genus Uronemella is redefined as follows: marine form with an
      elongate-elliptical or inverted pear-shaped body; apical plate conspicuous;
      buccal field about two-thirds of body length, cytostome subequatorially located;
      oral apparatus Uronema-like; somatic kineties comprising a mixture of dikinetids
      and monokinetids. Uronemella sinensis spec. nov. is recognized by having an
      elongate-elliptical body with truncated apical frontal plate, size in vivo about
      25-35 * 15-20 um, nine or ten somatic kineties, membranelle 1 consisting of two
      or three basal bodies, contractile vacuole pore at posterior end of somatic
      kinety 1. This study also compared the small-subunit rRNA gene sequences of these
      two species with other closely related species to show the sequence divergence,
      which ranged from 3.53 to 9.60%. Phylogenetic analyses support the contention
      that the genus Uronemella is monophyletic, while Metanophrys is non-monophyletic.

PMID- 23859948
TI  - Flaviramulus ichthyoenteri sp. nov., an N-acylhomoserine lactone-degrading
      bacterium isolated from the intestine of a flounder (Paralichthys olivaceus), and
      emended descriptions of the genus Flaviramulus and Flaviramulus basaltis.
AB  - A Gram-stain-negative, strictly aerobic, yellow-pigmented, rod-shaped and N
      acylhomoserine lactone-degrading bacterium, designated strain Th78(T), was
      isolated from the intestine of a cultured flounder (Paralichthys olivaceus).
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain
      Th78(T) belonged to the genus Flaviramulus (family Flavobacteriaceae) and showed
      the highest 16S rRNA gene sequence similarity to Flaviramulus basaltis H35(T)
      (96.70 %). Optimal growth occurred in the presence of 2-3 % (w/v) NaCl, at pH 7.0
      8.0 and at 28  degrees C. The major fatty acids were iso-C15 : 0 3-OH, iso-C15 :
      1 G and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine,
      one unidentified aminolipid and three unidentified polar lipids. Menaquinone 6
      (MK-6) was the only respiratory quinone. The DNA G+C content of strain Th78(T)
      was 31.5 mol%. On the basis of polyphasic analysis, strain Th78(T) is considered
      to represent a novel species of the genus Flaviramulus, for which the name
      Flaviramulus ichthyoenteri sp. nov. is proposed. The type strain is Th78(T) ( =
      JCM 18634(T) = KCTC 32142(T) = DSM 26285(T)). Emended descriptions of the genus
      Flaviramulus and Flaviramulus basaltis are also proposed. 

PMID- 23859949
TI  - No evidence from controlled trials to support the hypothesis that slow feeding
      advancement in preterm infants reduces the risk of necrotizing enterocolitis.
      Reply to the letter to the editor by S. Meyer and M. Butte: feeding regimens and
      necrotising enterocolitis [neonatology 2013;103:233-234].

PMID- 23859950
TI  - Occurrence of slipped capital femoral epiphysis in children undergoing
      gonadotropin-releasing hormone agonist therapy for the treatment of central
      precocious puberty.
AB  - BACKGROUND: Obesity, age and hormone imbalances including hypothyroidism and
      growth hormone deficiency and therapy, but not gonadotropin-releasing hormone
      agonist (GnRHa) therapy, have been identified as risk factors for slipped capital
      femoral epiphysis (SCFE). Five of 7 reported cases describe SCFE in children
      shortly after GnRHa therapy cessation. METHODS: We report 3 cases of SCFE that
      occurred in children on GnRHa therapy for the treatment of central precocious
      puberty (CPP) and discuss possible promoting factors. RESULTS: An otherwise
      healthy 8.75-year-old girl [body mass index (BMI) Z score +1.75] developed SCFE
      6.75 years into GnRHa therapy for idiopathic CPP. A second girl (with a history
      of acute lymphoblastic leukemia requiring total body irradiation) was 10.6 years
      old (BMI Z score +1.06) when she developed SCFE 3.3 years into GnRHa therapy. The
      third case was an 8.75-year-old female with CPP secondary to a hypothalamic
      hamartoma (BMI Z score +1.65) who developed bilateral SCFE 5.6 years into
      therapy. CONCLUSION: Increasing evidence suggests an association between GnRHa
      therapy for CPP and the occurrence of SCFE. We suggest that a lack of adequate
      sex hormone exposure at a 'critical period' of bone formation may result in a
      weakened epiphysis that becomes susceptible to slipping. (c) 2013 S. Karger AG,
      Basel.

PMID- 23859951
TI  - Viral hepatitis C gets personal--the value of human genomics to public health.
AB  - About 180 million people worldwide are chronically infected with hepatitis C
      virus (HCV), with 3-4 million newly infected each year. Only 15-25% of acute HCV
      infections clear spontaneously, and the remainder persists as chronic HCV
      infection. More than 350,000 people die every year from hepatitis C-related liver
      failure and cancer. There is currently no vaccine and the standard-of-care
      therapies--peg-interferon alpha (pegIFN) plus ribavirin (RBV)--are expensive and
      have serious side effects. Also, they may be effective in only 40-50% of patients
      infected with HCV genotype 1, the most common HCV genotype in the US. Interleukin
      28B (IL28B) genotype was recently and convincingly associated with response to
      pegIFN and RBV therapy. It has emerged as a robust pretreatment predictor of
      sustained virological response (SVR, i.e. virologic clearance) to pegIFN and RBV
      as well as to new triple therapy regimens that include a direct-acting antiviral
      agent with pegIFN and RBV and increase SVR rates as much as 75% in patients
      infected with HCV genotype 1. Testing for IL28B genotype may contribute to
      clinical decision-making and could inform clinical guidelines and public health
      policies.

PMID- 23859952
TI  - Androgen receptors in hormone-dependent and castration-resistant prostate cancer.
AB  - In the United States, prostate cancer (PCa) is the most commonly diagnosed non
      cutaneous cancer in males and the second leading cause of cancer-related death
      for men. The prostate is an androgen-dependent organ and PCa is an androgen
      dependent disease. Androgen action is mediated by the androgen receptor (AR), a
      hormone activated transcription factor. The primary treatment for metastatic PCa
      is androgen deprivation therapy (ADT). For the most part, tumors respond to ADT,
      but most become resistant to therapy within two years. There is persuasive
      evidence that castration resistant (also termed castration recurrent) PCa (CRPC)
      remains AR dependent. Recent studies have shown that there are numerous factors
      that contribute to AR reactivation despite castrate serum levels of androgens.
      These include changes in AR expression and structure through gene amplification,
      mutation, and alternative splicing. Changes in steroid metabolism, cell
      signaling, and coregulator proteins are also important contributors to AR
      reactivation in CRPC. Most AR targeted therapies have been directed at the
      hormone binding domain. The finding that constitutively active AR splice variants
      that lack the hormone binding domain are frequently expressed in CRPC highlights
      the need to develop therapies that target other portions of AR. In this review,
      the role of AR in normal prostate, in PCa, and particularly the mechanisms for
      its reactivation subsequent to ADT are summarized. In addition, recent clinical
      trials and novel approaches to target AR are discussed. 

PMID- 23859954
TI  - "Ligamentization" in hamstring tendon grafts after anterior cruciate ligament
      reconstruction: a systematic review of the literature and a glimpse into the
      future.
AB  - PURPOSE: The aims of this study were to provide a systematic review of the
      literature on "ligamentization" in hamstring tendon (HT) grafts after anterior
      cruciate ligament (ACL) reconstruction and analyze the postoperative remodeling
      process in human patients and animal models. METHODS: We performed a search in
      the Medline, PubMed, Embase and The Cochrane Library databases, followed by a
      manual search of reference lists to identify relevant articles. Only studies that
      investigated the ligamentization of hamstring grafts by histologic examination
      and comprehensively reported on the remodeling process were deemed eligible for
      review. RESULTS: A total of 4 studies were determined appropriate for systematic
      review: 2 of the included studies investigated human ACL grafts and 2 were
      performed in animal models. The studies included the examination of 79 human
      hamstring graft biopsy specimens and grafts of 27 skeletally mature sheep. To
      verify the remodeling process, authors reported on various aspects of
      cellularity, vascularity, and collagen organization. None of the included studies
      reached a level of evidence higher than 3. CONCLUSIONS: A postoperative
      ligamentization process can be found in HT grafts after ACL reconstruction and
      shows a typical progression through 3 distinguishable remodeling phases in humans
      and in animal models, whereas the progression and intensity of remodeling is
      distinctly increased in animals. CLINICAL RELEVANCE: Because postoperative
      remodeling influences biomechanical properties of hamstring grafts, a better
      understanding of this process and its timing could lead to substantial
      improvements in postoperative care strategies and indirectly to the optimization
      of surgical techniques.

PMID- 23859953
TI  - Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases:
      possible therapeutic targets?
AB  - Nitric oxide (NO) is synthetized enzymatically from l-arginine (l-Arg) by three
      NO synthase isoforms, iNOS, eNOS and nNOS. The synthesis of NO is selectively
      inhibited by guanidino-substituted analogs of l-Arg or methylarginines such as
      asymmetric dimethylarginine (ADMA), which results from protein degradation in
      cells. Many disease states, including cardiovascular diseases and diabetes, are
      associated with increased plasma levels of ADMA. The N-terminal catalytic domain
      of these NOS isoforms binds the heme prosthetic group as well as the redox
      cofactor, tetrahydrobiopterin (BH(4)) associated with a regulatory protein,
      calmodulin (CaM). The enzymatic activity of NOS depends on substrate and cofactor
      availability. The importance of BH(4) as a critical regulator of eNOS function
      suggests that BH(4) may be a rational therapeutic target in vascular disease
      states. BH(4) oxidation appears to be a major contributor to vascular dysfunction
      associated with hypertension, ischemia/reperfusion injury, diabetes and other
      cardiovascular diseases as it leads to the increased formation of oxygen-derived
      radicals due to NOS uncoupling rather than NO. Accordingly, abnormalities in
      vascular NO production and transport result in endothelial dysfunction leading to
      various cardiovascular disorders. However, some disorders including a wide range
      of functions in the neuronal, immune and cardiovascular system were associated
      with the over-production of NO. Inhibition of the enzyme should be a useful
      approach to treat these pathologies. Therefore, it appears that both a lack and
      excess of NO production in diseases can have various important pathological
      implications. In this context, NOS modulators (exogenous and endogenous) and
      their therapeutic effects are discussed.

PMID- 23859955
TI  - Psychosocial pathways to sexually transmitted infection risk among youth
      transitioning out of foster care: evidence from a longitudinal cohort study.
AB  - PURPOSE: To test the fit of a theoretically driven conceptual model of pathways
      to sexually transmitted infection (STI) risk among foster youth transitioning to
      adulthood. The model included (1) historical abuse and foster care experiences;
      (2) mental health and attachment style in late adolescence; and (3) STI risk in
      young adulthood. METHODS: We used path analysis to analyze data from a
      longitudinal study of 732 youth transitioning out of foster care. Covariates
      included gender, race, and an inverse probability weight. We also performed
      moderation analyses comparing models constrained and unconstrained by gender.
      RESULTS: Thirty percent reported they or a partner had been diagnosed with an
      STI. Probability of other measured STI risk behaviors ranged from 9% (having sex
      for money) to 79% (inconsistent condom use). Overall model fit was good
      (Standardized Root Mean Square Residual of .026). Increased risk of
      oppositional/delinquent behaviors mediated an association between abuse history
      and STI risk, via increased inconsistent condom use. There was also a borderline
      association with having greater than five partners. Having a very close
      relationship with a caregiver and remaining in foster care beyond age 18 years
      decreased STI risk. Moderation analysis revealed better model fit when
      coefficients were allowed to vary by gender versus a constrained model, but few
      significant differences in individual path coefficients were found between male
      and female-only models. CONCLUSIONS: Interventions/policies that (1) address
      externalizing trauma sequelae; (2) promote close, stable substitute caregiver
      relationships; and (3) extend care to age 21 years have the potential to decrease
      STI risk in this population.

PMID- 23859956
TI  - Assessment of DNA damage and lipid peroxidation in diabetic mice: effects of
      propolis and epigallocatechin gallate (EGCG).
AB  - There is growing recognition that polyphenolic compounds present in many plants
      and natural products may have beneficial effects on human health. Propolis - a
      substance produced by honeybees - and catechins in tea, in particular (-)
      epigallocatechin gallate (EGCG), are strong antioxidants that appear to have anti
      obesity and anti-diabetic effects. The present study was designed to elucidate
      the anti-diabetic effect of the water-soluble derivative of propolis (WSDP),
      which contains phenolic acids as the main compounds, and EGCG in alloxan-induced
      (75mg/kg, iv) diabetes in mice. Intraperitoneal administration of EGCG or
      propolis at doses of 50mg/kg body weight (bw) to diabetic mice for a period of 7
      days resulted in a significant increase in body weight and in
      haematological/immunological blood parameters, as well as in 100% survival of the
      mice. A significant decrease in lipid peroxidation in liver, kidney and brain
      tissue was also observed in diabetic mice treated with these two agents.
      Additionally, EGCG and propolis clearly reduced DNA damage in peripheral
      lymphocytes of diabetic mice. Our studies demonstrate the anti-oxidative and anti
      inflammatory potential of WSDP and EGCG, which could exert beneficial effects
      against diabetes and the associated consequences of free-radical formation in
      kidney, liver, spleen and brain tissue. The results suggest that dietary
      supplementation with WSDP or EGCG could potentially contribute to nutritional
      strategies for the prevention and treatment of diabetes mellitus. 

PMID- 23859957
TI  - Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs
      sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a
      cross-sectional, observational pilot study.
AB  - This cross-sectional, observational pilot study was designed to investigate the
      frequency of different endpoints of genotoxicity (sister-chromatid exchange,
      total chromosome aberrations, and micronucleus formation) and cytotoxicity
      (mitotic index, replication index, and nuclear division index) in the peripheral
      lymphocytes of patients with type-2 diabetes treated with different oral anti
      diabetic agents for 6 months. A total of 104 patients who met the American
      Diabetes Association criteria for type-2 diabetes were enrolled in the study. Of
      the 104 patients, 33 were being treated with sitagliptin (100mg/day), 25 with
      pioglitazone (30mg/day), 22 with rosiglitazone (4mg/day), and 24 with medical
      nutrition therapy (control group). The results for all the genotoxicity endpoints
      were significantly different across the four study groups. Post hoc analysis
      revealed that the genotoxicity observed in the sitagliptin group was
      significantly higher than that observed in the medical nutrition therapy group,
      but lower than that occurring in subjects who received thiazolidinediones. All of
      the three cytotoxicity endpoints were significantly lower in patients treated by
      oral anti-diabetic agents compared with those who received medical nutrition
      therapy. However, the three indexes did not differ significantly in the
      sitagliptin, rosiglitazone, and pioglitazone groups. Taken together, these pilot
      data indicate that sitagliptin and thiazolidinediones may exert genotoxic and
      cytotoxic effects in patients with type-2 diabetes. Further investigations are
      necessary to clarify the possible long-term differences between oral anti
      diabetic drugs in terms of genotoxicity and cytotoxicity, and how these can
      modulate the risk of developing diabetic complications in general and cancer in
      particular. 

PMID- 23859958
TI  - Mechanisms of functional recovery after stroke.
AB  - Stroke is a leading cause of disability. After initial stabilization, neurologic
      recovery takes place even in the acute phase. Well-known recovery mechanisms from
      stroke deficits are improvement from diaschisis, or functional reorganization of
      the ipsilesional or contralesional cortex with involvement of uncrossed
      corticospinal tract fibers. The importance of coactivation of the perilesional or
      contralesional cortex is unknown; however, neuronal plasticity plays an important
      role in neurologic recovery. With the recent advancements in knowledge regarding
      underlying mechanisms of neuronal plasticity, various functional modulating
      methods have been developed and studied in humans. In this review, basic
      mechanisms of functional recovery and potential targets for future research will
      be discussed. 

PMID- 23859959
TI  - Diagnostic approach to functional recovery: functional magnetic resonance imaging
      after stroke.
AB  - Stroke remains the most frequent cause of handicap in adult life and according to
      the WHO the second cause of death in the Western world. In the peracute phase,
      intravenous thrombolysis and in some cases endovascular therapy may induce early
      revascularization and hereby improve prognosis. However, only up to 20-25% of
      patients are eligible to causal treatment. Further, care in a specialized stroke
      unit improves prognosis in all patients independent of age and stroke severity.
      Even when it is not possible to prevent tissue loss, the surviving brain areas of
      functional brain networks have a substantial capacity to reorganize after a focal
      ischemic (or hemorrhagic) brain lesion. This functional reorganization
      contributes to functional recovery after stroke. Functional magnetic resonance
      imaging (fMRI) provides a valuable tool to capture the spatial and temporal
      activity changes in response to an acute ischemic lesion. Task-related as well as
      resting-state fMRI have been successfully applied to elucidate post-stroke
      remodeling of functional brain networks. This includes regional changes in
      neuronal activation as well as distributed changes in functional brain
      connectivity. Since fMRI is readily available and does not pose any adverse
      effects, repeated fMRI measurements provide unprecedented possibilities to
      prospectively assess the time course of reorganization in functional neural
      networks after stroke and relate the temporospatial dynamics of reorganization at
      the systems level to functional recovery. Here we review the current status and
      future perspectives of fMRI as a means of studying functional brain
      reorganization after stroke. We summarize (a) how fMRI has advanced our knowledge
      regarding the recovery mechanisms after stroke, and (b) how fMRI has been applied
      to document the effects of therapeutical interventions on post-stroke functional
      reorganization. 

PMID- 23859960
TI  - Diagnostic approach to functional recovery: diffusion-weighted imaging and
      tractography.
AB  - There is evidence showing that white matter changes are clinically relevant and
      can be associated with cognitive disorders, slower mental processing speed or
      motor impairment. The complex structural organization of the white matter can be
      depicted in vivo in great detail with advanced diffusion-weighted imaging (DWI).
      From the simplest and most commonly used technique (e.g. the mapping of apparent
      diffusion coefficient values) to more advanced techniques (e.g. diffusion tensor
      imaging), it is now possible to visualize white matter fibers of the brain in a
      noninvasive way. This chapter will first provide a basic understanding of the
      principles of these techniques and describe the current clinical applications of
      DWI and tractography in two common brain diseases, stroke and traumatic brain
      injury. We will emphasise on what these techniques may add to our understanding
      of the natural course of the pathology and especially, how they can help in
      predicting the outcomes of the rehabilitation phase. We will discuss how DWI and
      tractography techniques can shed light on possible compensatory disease
      mechanisms and propose future developments of these techniques in a clinical
      setting. 

PMID- 23859961
TI  - Compensatory contribution of the contralateral pyramidal tract after experimental
      cerebral ischemia.
AB  - Many people escape sudden death from ischemic brain stroke, but suffer from
      severe disabilities such as aphasia and/or paralysis. These survivors of focal
      brain injury need chronic care to recover from and/or compensate for the impaired
      sensory and motor functions previously controlled by the focal ischemic core.
      Functional compensation not only involves the remaining brain areas around the
      infarction but also the areas contralateral to the stroke lesion, with the need
      for remodeling of neuronal circuits in some cases. In this review, recent human
      and animal studies are presented to aid in the understanding of such plasticity
      in areas contralateral to the stroke lesion providing a new model for
      rehabilitation. It is well known in the medical field that the intact
      contralateral hemisphere is recruited for functional remodeling of modalities
      such as speech. However, the detailed mechanisms underlying these phenomena are
      less clear. In rodents, in vivo imaging techniques combined with other
      traditional techniques such as electrophysiology and behavior have revealed that
      functional recovery is achieved by specific synaptic (neuronal circuit)
      remodeling of the contralateral area in the 1st week after a focal stroke. The
      intact contralateral hemisphere can therefore potentially adopt a bilateral
      function, even in adults, following proper remodeling of neuronal circuits. These
      recent results suggest a possible new pathway using the intact hemisphere's
      function to recover lost functions stroke patients. 

PMID- 23859962
TI  - Compensatory contribution of the contralateral pyramidal tract after stroke.
AB  - Stroke is a leading cause of long-term disability with early accelerated followed
      by gradual recovery during the first 6 months after the ictus. The most important
      mechanism concerning early recovery is thought to be brain plasticity provided by
      anatomical and functional reorganization of the central nervous system after
      injury. Recent advances in noninvasive, functional brain imaging techniques
      provided some insight indicating the contribution of ipsilateral uncrossed
      corticospinal tracts in motor recovery after stroke. Since motor tracts vary
      considerably among subjects, the ratio of contralateral corticospinal tract
      fibers and their interhemispheric control versus the amount and function of
      ipsilateral corticospinal tract fibers may affect the scale of motor recovery
      after stroke. Further studies are needed to clarify the mechanisms of motor
      recovery after stroke in humans. 

PMID- 23859963
TI  - Regeneration of neuronal cells following cerebral injury.
AB  - Stem cells possess a definitive role in neuronal rejuvenation following a
      cerebral injury. Whether endogenous, from the neurogenic niches of the
      subventricular zone and subgranular zone, or recruited from the bone marrow
      through peripheral circulation, accumulating evidence demonstrates that stem
      cells ameliorate the consequences of cerebrovascular events, particularly
      cerebral ischemia. In this chapter, we review milestone studies implicating the
      role of stem cells in response to disease. Furthermore, we outline specific
      mechanisms of action along with their clinical potential as therapeutic
      treatments for ischemic stroke. 

PMID- 23859964
TI  - Translational challenge for bone marrow stroma cell therapy after stroke.
AB  - There is increasing evidence that the transplanted bone marrow stromal cells
      (BMSC) significantly promote functional recovery after central nervous system
      (CNS) damage in the animal models of various kinds of CNS disorders, including
      cerebral infarct. However, there remain several challenges before considering
      BMSC transplantation for patients with ischemic stroke. In this review,
      therefore, the authors discuss what should be clarified to establish cell
      transplantation therapy in the clinical setting and describe their scientific
      contributions in this matter. The BMSC have the ability to alter their gene
      expression profile and phenotype in response to the surrounding environment and
      to protect the neurons by producing certain neurotrophic factors. They also
      promote neurite extension and rebuild the neural circuits in the injured CNS. The
      BMSC can be expanded in vitro using the animal serum-free medium. Pharmacological
      modulation may accelerate the in vitro proliferation of the BMSC. Using in vivo
      optical imaging technique and MRI, the transplanted BMSC can noninvasively be
      tracked in the living animal for at least 8 weeks after transplantation. It is
      urgent to develop a clinical imaging technique to track the transplanted cells in
      the CNS and evaluate the therapeutic significance of BMSC transplantation in
      order to establish it as a definite therapeutic strategy in the clinical setting
      in the future. 

PMID- 23859965
TI  - Experimental evidence and early translational steps using bone marrow derived
      stem cells after human stroke.
AB  - Neurogenesis is principally restricted to the subventricular zone of the lateral
      ventricle wall and the subgranular zone of the hippocampal dentate gyrus in
      physiological situations. However, neuronal stem cells are known to be mobilized
      into the post- and peristroke area and we have demonstrated that appropriate
      support of these stem cells, achieved by therapeutic angiogenesis, enhances
      neuroregeneration followed by neuronal functional recovery in an experimental
      stroke model. We also found that neural stem cells are mobilized in patients
      after stroke, as well as in animal models. Based on these observations, we have
      started cell-based therapy using autologous bone marrow-derived stem/progenitor
      cells in patients after stroke. This review summarizes the findings of recent
      experimental and clinical studies that have focused on neurogenesis in the
      injured brain after cerebral infarction. We also refer to the challenges for
      future cell-based therapy, including regeneration of the aged brain. 

PMID- 23859966
TI  - Therapeutic drug approach to stimulate clinical recovery after brain injury.
AB  - The identification of strategies by which the central nervous system (CNS) can
      transform itself in response to injury has incited the systematic exploration of
      methods to enhance neurological recovery after CNS injury. Several
      pharmaceuticals have been shown to promote such recovery; however, more rigorous
      clinical trials are necessary to establish their clinical relevance. The major
      impediment for these strategies in the clinical arena is the astounding
      heterogeneity surrounding neuroplasticity and regeneration. Tolerance to injury
      and varied rates of recovery are likely governed by genetic and environmental
      factors that remain largely elusive. The extraordinary complexity of the neural
      networks in the CNS impedes the assessment of 'plain' pharmacological
      interventions in therapeutic trials. 'Proof-of-principle' studies of
      pharmacological interventions enhancing neuroplasticity or regeneration may
      therefore at first focus on surrogate markers, such as functional MRI,
      magnetoencephalography and diffusion tensor imaging, or investigate seemingly
      more uniform systems, such as spinal cord injuries. The discovery that
      experimental adult CNS lesions can essentially regenerate has rejected the
      conviction that adult axon injury is always permanent and spurred research into
      determining whether the circumstances under which such regeneration occurs can be
      created in human CNS injury. The hostility of the microenvironment preventing
      axonal regrowth has been linked to key molecular targets involving myelin
      associated factors and glial scar components. While the mechanisms involved are
      better understood now and potential therapeutic targets are identified, the
      crucial question whether manipulating the molecular regulation of axonal repair
      is feasible and will benefit patients remains uncertain. While factual repair of
      brain tissue may still be years away, research into the mechanisms of adaptation
      after brain injury offers more tangible return on the short run. 

PMID- 23859967
TI  - Rehabilitation and plasticity.
AB  - Therapies for effective neurorehabiltiation are in part based on brain mechanism
      commonly described as neuroplasticity. These therapeutic approaches emphasize the
      re-learning of functionality that was lost due to the injury through
      reorganization of neural circuits in the remaining intact tissue. Important
      elements of these therapies are intensive and repetitive training, motivation and
      potentially interactive devices (therapy "robots") and supportive therapies such
      as brain stimulation or plasticity inducing medications. Because neuroplasticity
      based interventions are complex and multifactorial optimized treatment protocols
      have to be developed before large clinical trials can provide the evidence of
      efficacy. 

PMID- 23859968
TI  - A brain-computer interface to support functional recovery.
AB  - Brain-computer interfaces (BCI) register changes in brain activity and utilize
      this to control computers. The most widely used method is based on registration
      of electrical signals from the cerebral cortex using extracranially placed
      electrodes also called electroencephalography (EEG). The features extracted from
      the EEG may, besides controlling the computer, also be fed back to the patient
      for instance as visual input. This facilitates a learning process. BCI allow us
      to utilize brain activity in the rehabilitation of patients after stroke. The
      activity of the cerebral cortex varies with the type of movement we imagine, and
      by letting the patient know the type of brain activity best associated with the
      intended movement the rehabilitation process may be faster and more efficient.
      The focus of BCI utilization in medicine has changed in recent years. While we
      previously focused on devices facilitating communication in the rather few
      patients with locked-in syndrome, much interest is now devoted to the therapeutic
      use of BCI in rehabilitation. For this latter group of patients, the device is
      not intended to be a lifelong assistive companion but rather a 'teacher' during
      the rehabilitation period. 

PMID- 23859969
TI  - Novel methods to study aphasia recovery after stroke.
AB  - The neural mechanisms that support aphasia recovery are not yet fully understood.
      It has been argued that the functional reorganization of language networks after
      left-hemisphere stroke may engage perilesional left brain areas as well as
      homologous right-hemisphere regions. In this chapter, we summarize how
      noninvasive brain stimulation can be used to elucidate mechanisms of plasticity
      in language networks and enhance language recovery after stroke. We first outline
      some basic principles of transcranial magnetic stimulation (TMS) and transcranial
      direct current stimulation (tDCS). We then present evidence from studies in
      healthy volunteers for a causal role of the right hemisphere in different
      language functions. Finally, we review recent studies that used TMS or tDCS to
      promote language recovery after stroke. Most of these studies applied noninvasive
      brain stimulation over contralateral right-hemisphere areas to suppress
      maladaptive plasticity. However, some studies also suggest that right-hemisphere
      regions may beneficially contribute to recovery in some patients. More recently,
      some investigators have targeted perilesional brain regions to promote
      neurorehabilitation. In sum, these studies indicate that language recovery after
      stroke may integrate left- as well as right-hemisphere brain regions to a
      different degree over the time course of recovery. Although the results of these
      preliminary studies provide some evidence that noninvasive brain stimulation may
      promote aphasia recovery, the reported effect sizes are not striking. Future
      studies on larger patient collectives are needed to explore whether noninvasive
      brain stimulation can enhance language functions at a level that is clinically
      relevant. 

PMID- 23859970
TI  - Role of repetitive transcranial magnetic stimulation in stroke rehabilitation.
AB  - In recent years, efforts have focused on investigating the neurophysiological
      changes that occur in the brain after stroke, and on developing novel strategies
      such as additional brain stimulation to enhance sensorimotor and cognitive
      recovery. In the 1990s, repetitive transcranial magnetic stimulation (rTMS) was
      introduced as a therapeutic tool for improving the efficacy of rehabilitation for
      recovery after stroke. It is evident that disturbances of interhemispheric
      processes after stroke result in a pathological hyperactivity of the intact
      hemisphere. The rationale of using rTMS as a complementary therapy is mainly to
      decrease the cortical excitability in regions that are presumed to hinder optimal
      recovery by low-frequency rTMS delivered to the unaffected hemisphere, while high
      frequency rTMS delivered to the affected hemisphere facilitates cortical
      excitability. However, the exact mechanisms of how rTMS works are still under
      investigation. There is a growing body of research in stroke patients
      investigating the effect of rTMS on facilitating recovery by modifying cortical
      and subcortical networks. Clinical trials applying rTMS already yielded promising
      results in improving recovery of sensorimotor and cognitive functions.
      Altogether, in combination with conventional therapeutic approaches, rTMS has a
      potential to become a complementary strategy to enhance stroke recovery by
      modulating the excitability of targeted brain areas. In future studies, emphasis
      should be placed on selecting patient populations to determine whether treatment
      response depends on age, lesion acuteness, or stroke severity. Furthermore, it is
      important to identify parameters optimizing the beneficial effects of rTMS on
      stroke recovery, and to monitor their long-term effects. 

PMID- 23859971
TI  - Influence of therapeutic hypothermia on regeneration after cerebral ischemia.
AB  - The protective effect of therapeutic hypothermia in cerebral ischemia is well
      accepted in experimental models, and some clinical studies show that there is
      benefit in humans as well. Long-term observations in animal and clinical studies
      have documented recovery of neurological function following hypothermia
      treatment. Diminished damage by hypothermic protection should contribute to the
      recovery in many ways, but hypothermia appears to enhance regeneration of brain
      tissue as well. Since regeneration of the brain after damage initiates within
      hours and is active days and weeks after stroke, prolonged hypothermia might
      affect regenerative processes which have been documented to occur in these time
      frames. As there is a lack of data at the basic and clinical levels, the
      mechanism of neuroregeneration by hypothermia is unclear. Yet, we speculate that
      hypothermia enhances regeneration by positively influencing neurogenesis,
      angiogenesis, gliogenesis and synapse/circuit formation after stroke. In this
      chapter, we will provide up-to-date data from experimental studies and clinical
      reports on the effect of therapeutic hypothermia on neuroregeneration, with
      perspectives on future research. 

PMID- 23859972
TI  - High voltage electric potentials to enhance brain-derived neurotrophic factor
      levels in the brain.
AB  - Development of a safe method to increase brain-derived neurotrophic factor (BDNF)
      levels in the brain is expected to enhance learning and memory, induce tolerance
      to cerebral infarction or tolerance to depressive state, improve glucose
      metabolism, and suppress appetite and body weight. We have shown that repetitive
      applications of high-voltage electric potential (HELP) to the body increase BDNF
      levels in the brain, improving learning and memory in mice. Here, we investigated
      the effects of HELP treatment for a chronic period on the BDNF levels in the
      mouse brain, and on body weight in mice and humans. Adult mice were exposed to
      3.1 or 5.4 kV HELP (on the body), 5 h a day for 24 weeks, and BDNF levels in the
      brain and alterations in body weight were analyzed. Humans [age, 53.2 +/- 15.5
      years old; BMI, 27.8 +/- 5.6 (mean +/- SD, n = 6)] were exposed to 3.9 kV HELP
      (on the body) for 1 h a day, continuing for 33 months (2.8 years) under the
      monitor of body weight. In mice, the HELP application elevated BDNF levels in the
      brain at least temporarily, affecting body weight in a voltage- and time
      dependent manner. In humans, the HELP treatment reduced body weight compared to
      the pretreated initial values without any aversive effects (p < 0.002, one-way
      ANOVA with the post hoc Holm-Sidak test). The results in mice indicated that 3.1
      kV HELP was considered insufficient for a continuous elevation of intracerebral
      BDNF, and 5.4 kV HELP was considered as excessive. HELP with an appropriate
      voltage can be utilized to increase BDNF levels in the brain for a prolonged
      period. We anticipate further investigations to clarify the effect of the optimal
      leveled HELP therapy on memory disturbances, neurological deficits after stroke,
      depression, diabetes, obesity and metabolic syndrome. 

PMID- 23859973
TI  - Prevention of post-stroke disuse muscle atrophy with a free radical scavenger.
AB  - In spite of appropriate treatment in the acute phase of stroke, quite a few
      patients with hemiparetic stroke become disabled and stay in a wheelchair or
      bedridden state in the chronic phase. In stroke patients, gait dysfunction
      results mainly from severe hemiparesis due to ischemic damage to the motor neuron
      tract and partly from disuse muscle atrophy in paretic and nonparetic legs.
      Disuse muscle atrophy occurs even in healthy subjects as early as 4 days after
      bed rest immobilization and progresses further correlating with the duration of
      immobilization. Although detailed mechanisms of disuse muscle atrophy remain
      unclear, free radical scavengers are known to play an important role in the
      development of disuse muscle atrophy. One of the neuroprotective agents,
      edaravone, a free radical scavenger, succeeded in proving clinical usefulness in
      a phase III clinical trial in Japan. In this trial, stroke patients were
      administered edaravone for 14 days consecutively. The results of the edaravone
      trial are taken to indicate that long-term administration of a free radical
      scavenger may prevent disuse atrophy thereby improving functional outcome. We
      performed a randomized pilot study in hemiparetic stroke patients to test the
      validity of this view. Acute stroke patients were randomly allocated to two
      groups, one receiving edaravone for 3 days (short-term group) and the other for
      10-14 days (long-term group). At 3 months after stroke, the grade of femoral
      muscle atrophy was significantly milder and the maximum walking speed was
      significantly faster in the long-term group than in the short-term group. The
      study suggests that long-term administration of a free radical scavenger may
      prevent the development of leg disuse atrophy thereby ameliorating locomotor
      function. Attention should be paid to myoprotective drug therapy in acute stroke,
      since it may be easier and clinically more effective than neuroprotective therapy
      from the viewpoint of functional prognosis. 

PMID- 23859975
TI  - Clinical recovery from CNS damage. Preface.

PMID- 23859976
TI  - Absorption in self-selected activities is associated with lower ambulatory blood
      pressure but not for high trait ruminators.
AB  - BACKGROUND: A range of nonpharmacological interventions (e.g., meditation) have
      positive effects on blood pressure (BP) but tend to have poor adherence. These
      interventions may lower BP partly by absorbing and directing attention away from
      one's negative thoughts. We hypothesized that recurring self-selected activities
      (SSAs) that are attentionally absorbing may similarly lower BP. We examined the
      effect of reported engagement in SSAs during the previous month prior to
      participation on ambulatory BP (ABP) and whether those prone to rumination were
      less likely to show these effects. METHODS: Participants (n = 38) reported
      engagement in SSAs and how absorbing they were, responded to trait rumination and
      perceived stress questionnaires, wore an ABP monitor for 24 hours, and at each
      ABP measurement answered electronic diary questions assessing activity levels,
      affect, social interactions, and caffeine and tobacco use. RESULTS: Regression
      analyses tested whether the reported absorption of SSAs, trait rumination, and
      their interaction predicted daytime and nighttime systolic and diastolic ABP.
      Greater absorption predicted lower daytime and nighttime ABP (bs = -18.83 to 
      8.79; Ps < .05), but this relationship was moderated by trait rumination (bs =
      3.72 to 9.97; Ps < .05). Follow-up analyses revealed that absorption was
      unrelated to ABP for those with high trait rumination but that more absorption
      predicted lower ABP for those less prone to rumination. CONCLUSIONS: Our results
      suggest that regular engagement in absorbing SSAs is related to lower ABP. These
      findings have implications for the development of nonpharmacological
      interventions and suggest SSAs may serve as an adjuvant intervention strategy to
      lower BP.

PMID- 23859977
TI  - Catatonia after deep brain stimulation successfully treated with lorazepam and
      right unilateral electroconvulsive therapy: a case report.
AB  - OBJECTIVES: The presence of a deep brain stimulator (DBS) in a patient who
      develops neuropsychiatric symptoms poses unique diagnostic challenges and
      questions for the treating psychiatrist. Catatonia has been described only once,
      during DBS implantation, but has not been reported in a successfully implanted
      DBS patient. METHODS: We present a case of a patient with bipolar disorder and
      renal transplant who developed catatonia after DBS for essential tremor. RESULTS:
      The patient was successfully treated for catatonia with lorazepam and
      electroconvulsive therapy after careful diagnostic workup. Electroconvulsive
      therapy has been successfully used with DBS in a handful of cases, and certain
      precautions may help reduce potential risk. CONCLUSIONS: Catatonia is a rare
      occurrence after DBS but when present may be safely treated with standard
      therapies such as lorazepam and electroconvulsive therapy.

PMID- 23859978
TI  - Successful use of right unilateral ECT for catatonia: a case series.
AB  - Catatonia is a neuropsychiatric syndrome involving motor signs in association
      with disorders of mood, behavior, or thought. Bitemporal electrode placement
      electroconvulsive therapy (ECT) is a proven effective treatment for catatonia,
      and this mode of ECT delivery is the preferred method of treatment in this
      condition. Studies in major depressive disorder have demonstrated that
      suprathreshold, nondominant (right) hemisphere, unilateral electrode placement
      ECT has fewer adverse effects, especially cognitive adverse effects, than
      bitemporal ECT. This case series describes the use of right unilateral (RUL) ECT
      in 5 patients with catatonia. Before ECT, all 5 patients in this series initially
      failed therapy with benzodiazepines and psychotropic medications. Each catatonic
      patient received a series of 8 to 12 RUL ECT in an every-other-day series. After
      ECT, 4 of the 5 patients had a full recovery from catatonia. One patient achieved
      only partial response to RUL ECT, and no additional benefit was obtained with
      bitemporal ECT. All patients in this case series tolerated RUL ECT without major
      adverse effects. This case series illustrates successful use of RUL ECT in
      patients with catatonia and adds to the early literature demonstrating its
      effective use in treating this complex condition. 

PMID- 23859979
TI  - Does comorbid alcohol and substance abuse affect electroconvulsive therapy
      outcome in the treatment of mood disorders?
AB  - INTRODUCTION: Antidepressant medications remain the principal agents used to
      treat patients with mood disorders, although 30% to 40% of these patients do not
      improve. One of the factors associated with poor medication response is alcohol
      and substance abuse. Persons with mood disorders are at the greatest risk for
      suicide, and alcoholism is a significant additional risk factor.
      Electroconvulsive therapy (ECT) is shown to be the most effective treatment for
      major depression especially when associated with psychosis, catatonia, and
      suicide intent. However, similar to most antidepressant trials, patients with
      depression and comorbid alcohol and substance abuse are excluded from ECT
      efficacy studies. METHOD: Through a retrospective chart review, we compared
      response to ECT in patients with mood disorder and comorbid alcohol and drug
      abuse to those with mood disorder only. From 2004 to 2010, 80 patients with mood
      disorder received ECT. Fifty of these had comorbid alcohol or drug abuse. Using a
      10-item psychopathology scale, we compared pre- and post-ECT symptom severity
      between the 2 groups. Outcome was determined by measuring a decrease in the pre
      ECT and post-ECT score using Wilcoxon rank tests, with statistical significance
      at P = 0.05. RESULTS: There was no difference between the 2 groups in most
      demographics, ECT medication, or seizure quality. There was no difference in ECT
      outcome between those with comorbid alcohol abuse and those without based on
      percent decrease in pre- and post-ECT symptom scores (abuse: mean [SD], 0.89
      [0.2] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 1332; P = 0.086). When we
      compared those who met the criteria for alcohol or drug dependence (19 patients)
      with those with no abuse, there was a trend for the dependence group to not do as
      well (dependence: mean [SD], 0.83 [0.25] vs nonabuse: mean [SD], 0.93 [0.16];
      Wilcoxon, 405; P = 0.053). Those with combined drug and alcohol abuse (18
      patients) did have a significantly worse outcome (combined: mean [SD], 0.82
      [0.25] vs nonabuse: mean [SD], 0.93 [0.16]; Wilcoxon, 372; P = 0.033).
      CONCLUSION: Our results indicate that comorbid alcohol and drug abuse may
      influence the response to ECT in the treatment of mood disorders. Based on our
      results, patients with comorbid dependence and combined drug and alcohol abuse
      showed symptom improvement but did not do as well as those with nonabuse.

PMID- 23859980
TI  - Antipsychotic polypharmacy in a treatment-refractory schizophrenia population
      receiving adjunctive treatment with electroconvulsive therapy.
AB  - BACKGROUND: Antipsychotic polypharmacy (APP) is frequent, but its pattern is
      unknown in treatment-refractory schizophrenia-spectrum patients receiving
      electroconvulsive therapy (ECT). METHODS: We performed a retrospective chart
      review of ECT-treated inpatients hospitalized at 2 Danish University hospitals
      from 2003 to 2008, focusing on APP patterns in patients with schizophrenia
      spectrum disorders (n = 79, 13.2%). In addition to univariate analyses, a
      multivariate logistic regression analysis was performed to identify independent
      predictors of APP. RESULTS: Of 79 antipsychotic-treated patients (aged 48.6 +/-
      14.2 years; illness duration, 18.3 +/- 10.6 years) ultimately treated with ECT,
      86.1% received 2 or more psychotropic medications, including mood stabilizers
      (19.0%), antidepressants (32.9%), and APP (72.2%; 2 antipsychotics = 41.8%, 3 =
      21.5%, 4-5 = 7.6%). Most patients received first-generation antipsychotic (FGA) +
      second-generation antipsychotic (SGA) (48.1%), followed by SGA + SGA (24.1%), SGA
      monotherapy (22.8%), and FGA monotherapy (5.1%). Individual antipsychotics
      included olanzapine (44.3%), risperidone (26.6%), clozapine (26.6%), quetiapine
      (22.1%), ziprasidone (13.9%), aripiprazole (10.1%), and sertindole (3.8%).
      Antipsychotic polypharmacy was associated with a greater number of FGAs (0.8 +/-
      0.7 vs 0.1 +/- 0.4, P < 0.0001) and SGAs (1.7 +/- 0.8 vs 0.8 +/- 0.4, P <
      0.0001), zuclopenthixol use (31.6% vs 0%, P = 0.0019), olanzapine use (52.6% vs
      22.7%, P = 0.017), less serotonin-noradrenaline reuptake inhibitor use (3.5% vs
      18.2%, P = 0.027), and a trend toward more good to excellent ECT response (86.0%
      vs 68.2%, P = 0.071). In the logistic regression analysis, APP was independently
      associated with a higher number of FGAs (P = 0.0002) and olanzapine use (P =
      0.0098) (r = 0.314, P < 0.0001). DISCUSSION: Only 22.6% of this treatment
      refractory population received clozapine, yet 72.4% received APP. Following the
      results from our study as well as the general level of evidence, patients with
      refractory schizophrenia-spectrum disorder should receive clozapine or ECT before
      being tried on APP.

PMID- 23859982
TI  - Reply to John Samuel Banerji's letter to the editor re: Constantijn H.J.
      Muselaers, Otto C. Boerman, Egbert Oosterwijk, Johannes F. Langenhuijsen, Wim
      J.G. Oyen, Peter F.A. Mulders. Indium-111-labeled girentuximab immunoSPECT as a
      diagnostic tool in clear cell renal cell carcinoma. Eur Urol 2013;63:1101-6.

PMID- 23859983
TI  - Microwave-assisted hydrolysis of polysaccharides over polyoxometalate clusters.
AB  - Polyoxometalate (POM) clusters were utilized as recyclable acid catalysts and
      microwave-absorbing agents for the microwave-assisted hydrolysis of corn starch
      and crystalline cellulose. Phosphotungstic (PW) and silicotungstic (SiW) acids
      showed high hydrolyzing activity, while phosphomolybdic acid (PMo) showed lower
      glucose stability. The PW catalyst could be recycled by ether extraction at least
      4 times without changing its catalytic activity. The addition of PW could reduce
      the energy demand required for running the hydrolysis by 17-23%. The dielectric
      property of the aqueous PW solution was important for increasing the microwave
      absorption capability of the reaction system and reducing the energy consumption.

PMID- 23859984
TI  - Analysis of oxygen reduction and microbial community of air-diffusion biocathode
      in microbial fuel cells.
AB  - Microbes play irreplaceable role in oxygen reduction reaction of biocathode in
      microbial fuel cells (MFCs). In this study, air-diffusion biocathode MFCs were
      set up for accelerating oxygen reduction and microbial community analysis. Linear
      sweep voltammetry and Tafel curve confirmed the function of cathode biofilm to
      catalyze oxygen reduction. Microbial community analysis revealed higher diversity
      and richness of community in plankton than in biofilm. Proteobacteria was the
      shared predominant phylum in both biofilm and plankton (39.9% and 49.8%) followed
      by Planctomycetes (29.9%) and Bacteroidetes (13.3%) in biofilm, while
      Bacteroidetes (28.2%) in plankton. Minor fraction (534, 16.4%) of the total
      operational taxonomic units (3252) was overlapped demonstrating the
      disproportionation of bacterial distribution in biofilm and plankton.
      Pseudomonadales, Rhizobiales and Sphingobacteriales were exoelectrogenic orders
      in the present study. The research obtained deep insight of microbial community
      and provided more comprehensive information on uncultured rare bacteria. 

PMID- 23859985
TI  - Electricity generation from food wastes and microbial community structure in
      microbial fuel cells.
AB  - Microbial fuel cell (MFC) was studied as an alternate and a novel way to dispose
      food wastes (FWs) in a waste-to-energy form. Different organic loading rate
      obviously affected the performance of MFCs fed with FWs. The maximum power
      density of ~18 W/m(3) (~556 mW/m(2)) was obtained at COD of 3200+/-400 mg/L and
      the maximum coulombic efficiency (CE) was ~27.0% at COD of 4900+/-350 mg/L. The
      maximum removals of COD, total carbohydrate (TC) and total nitrogen (TN) were
      ~86.4%, ~95.9% and ~16.1%, respectively. Microbial community analysis using 454
      pyrosequencing of 16S rRNA gene demonstrated the combination of the dominant
      genera of the exoelectrogenic Geobacter and fermentative Bacteroides effectively
      drove highly efficient and reliable MFC systems with functions of organic matters
      degradation and electricity generation.

PMID- 23859986
TI  - Analysis of the stability of high-solids anaerobic digestion of agro-industrial
      waste and sewage sludge.
AB  - The pilot-scale high-solids anaerobic digestion (HS-AD) of agro-industrial wastes
      and sewage sludge was analysed in terms of stability by monitoring the most
      common parameters used to check the performance of anaerobic digesters, i.e.
      Volatile Fatty Acids (VFA), ammonia nitrogen, pH, alkalinity and methane
      production. The results reflected similar evolution for the parameters analysed,
      except for an experiment that presented an unsuccessful start-up. The rest of the
      experiments ran successfully, although the threshold values proposed in the
      literature for the detection of an imbalance in wet processes were exceeded,
      proving the versatility of HS-AD to treat different wastes. The results evidence
      the need for understanding the dynamics of a high-solids system so as to detect
      periods of imbalance and to determine inhibitory levels for different compounds
      formed during anaerobic decomposition. Moreover, the findings presented here
      could be useful in developing an experimental basis to construct new control
      strategies for HS-AD. 

PMID- 23859987
TI  - Sewage sludge biochar as an efficient catalyst for oxygen reduction reaction in
      an microbial fuel cell.
AB  - Sewage sludge (SS) biochars have been prepared under an inert atmosphere at
      different temperatures. Morphologic and chemical analyses reveal that the surface
      of the biochar carbonized at 900 degrees C (SS900) has more abundant micropores,
      and higher nitrogen and iron contents as compared to those carbonized at 500
      (SS500) and 700 degrees C (SS700). The electrochemical analyses display that the
      prepared biochars are active for catalyzing oxygen reduction reaction (ORR).
      However, more positive peak potential and larger peak current of ORR are found
      using the SS900 as compared to the SS500 and SS700. In MFCs, the maximum power
      density of 500+/-17 mW m(-2) was obtained from the SS900 cathode, which is
      comparable to the Pt cathode. The proposed cathode exhibited good stability and
      great tolerance to methanol. Given these results, it is expected that the SS
      derived biochar cathode can find application in fuel cell systems.

PMID- 23859988
TI  - Removal of chromium and lead by a sulfate-reducing consortium using peat moss as
      carbon source.
AB  - The effect of pre-treated peat moss on the ability of a sulfate-reducing
      microbial consortium to remove chromium and lead in solution was evaluated. The
      most active bacterial community (235.7 mmol H2S/g VSS) was selected from among
      eight consortia. The peat moss was pre-treated with different HCl concentrations
      and contact times. The best combination of treatments was 20% HCl for 10 min. The
      constant substrate affinity Ks was 740 mg COD/L and the ratio COD/SO4(2-) was
      0.71. At pH 5, higher production of biogenic sulfide was observed. The up
      flowpacked bed bioreactor operated at a flow of 8.3 mL/min for 180 h to obtain
      removal efficiency (by sulfate-reducing activity) of 90% lead and 65% chromium.
      It is important to consider that peat moss is a natural adsorbent that further
      influences the removal efficiency of metal ions.

PMID- 23859990
TI  - The Central Society for Clinical and Translational Research: more than just a
      name change.

PMID- 23859989
TI  - MicroRNA regulation of integrins.
AB  - MicroRNAs (miRNAs) are a family of small RNAs that are ~20 nucleotides in length
      and are nontranslated. To date, more than 700 miRNAs have been identified, and
      their involvement in many essential cellular processes is now apparent. By
      binding with target messenger RNAs (mRNA), miRNAs are able to regulate both mRNA
      stability and mRNA translational efficiency. Integrins are a family of
      transmembrane proteins that both regulate cell matrix interactions and serve as
      receptors that mediate intracellular signaling and a variety of cellular
      processes, including inflammatory responses, immunoresponses, and tumorigenesis.
      Integrin expression may also be regulated by miRNAs, which can also modulate
      integrin signaling and function. Integrins are heterodimer adhesion proteins
      comprised of an alpha and a beta subunit. Cumulatively, there are 18 alpha
      subunits and 8 beta subunits that can combine to form 24 distinct alphabeta
      receptor complexes. In addition, each integrin can be classified into 1 of 4
      groups based on its extracellular binding ligand: collagen, laminin, RGD (Arg-Gly
      Asp) or leukocyte-specific receptors. Collagen ligand integrins include integrins
      alpha1 and alpha2 subunits, known to be regulated by specific miRNAs. Among the
      laminin ligand integrins, there are no integrin alpha subunits known to be
      regulated by miRNA. As for the RGD ligand integrins, integrin alpha5 is the only
      alpha subunit found to be regulated by miRNAs (miR-31, miR-17-92 cluster, and miR
      148 b). Finally, among the alpha subunits that comprise the leukocyte-specific
      receptor ligand integrins, integrins alphaD, alphaL, alphaM, and alphaX have
      shown regulation by different miRNAs. As for the integrin beta subunits,
      regulation by miRNAs has been reported for all but beta5 and beta6 to date.
      However, computational predictions suggest that numerous miRNAs potentially
      regulate a variety of target integrins. These predictions will undoubtedly guide
      future investigations of mechanisms underlying integrin expression mechanism and
      may ultimately yield new therapeutic tools.

PMID- 23859991
TI  - Comment on 'accuracy of segmental multi-frequency bioelectrical impedance
      analysis for assessing whole-body and appendicular fat mass and lean soft tissue
      mass in frail women aged 75 years and older'.

PMID- 23859992
TI  - Morbid obesity after spinal cord injury: an ailment not to be treated?
AB  - A 28-year-old man with a T12 incomplete paraplegia after a spinal cord injury
      (SCI) was referred for weight management in October 2011. He reported a weight
      gain from about 120 to 180.3 kg since his SCI. He put on a further 11.4 kg in
      January 2012 despite intensive dietetic treatment, including very low-caloric
      diet, anti obesity medication and active physiotherapy programme. He had
      undergone an uncomplicated laparoscopic Roux-en-Y gastric bypass successfully in
      March 2012. For the first 7 months after surgery, his total weight loss was 32.4
      kg. He has shown functional improvement (6 min walking distance and Berg balance
      score). There were important improvements in body mass index; waist
      circumference; mid-upper arm circumference; triceps-skinfold thickness; mid-arm
      muscle circumference; total cholesterol; high-density lipoprotein-cholesterol;
      and low-density lipoprotein-cholesterol and triglycerides. This report describes
      the first UK morbidly obese SCI patient who has undergone gastric bypass surgery
      and highlights the provision of bariatric surgery as an option to consider if all
      nonsurgical interventions have been tried. 

PMID- 23859993
TI  - Consumption of coffee, not green tea, is inversely associated with arterial
      stiffness in Japanese men.
AB  - BACKGROUND/OBJECTIVES: Studies on the associations between coffee and green tea
      consumption and arterial stiffness are rare. This study evaluated the possible
      relationships between coffee and green tea consumption and brachial-ankle pulse
      wave velocity (ba-PWV) values in Japanese men. SUBJECTS/METHODS: In total, 540
      eligible men who enrolled in the baseline survey of a cohort study in Tokushima
      Prefecture, Japan, and who underwent ba-PWV measurement were analyzed.
      Information about lifestyle characteristics including coffee and green tea intake
      were obtained from a structural self-administered questionnaire. Multiple linear
      regression analyses were used to evaluate the associations between coffee and
      green tea consumption and ba-PWV. RESULTS: Subjects with greater coffee
      consumption were younger and showed higher proportions of current smoking and
      alcohol consumption. Subjects with greater green tea consumption were older and
      showed lower proportions of current smoking and alcohol consumption. Greater
      coffee consumption was significantly inversely associated with ba-PWV after the
      adjustment for probable covariates, including serum low-density lipoprotein
      cholesterol and high-density lipoprotein cholesterol (P for trend =0.031). After
      additional adjustment for serum triglycerides, this inverse association
      persisted, but was somewhat attenuated (P for trend =0.050). In contrast, green
      tea consumption was not associated with ba-PWV. CONCLUSIONS: Coffee consumption
      was inversely associated with arterial stiffness independent of known
      atherosclerotic risk factors, and this association was partly mediated by reduced
      circulating triglycerides. Further prospective or interventional studies are
      needed to confirm the causal association.

PMID- 23859994
TI  - The effect of acute moderate-intensity exercise on the accuracy of air
      displacement plethysmography in young adults.
AB  - BACKGROUND/OBJECTIVES: Air-displacement plethysmography (ADP) body composition
      systems utilize a precise pre-test protocol that must be followed for each trial.
      Previous research has shown that body temperature changes influence the results
      when using ADP as a measurement. The objective of this study is to determine the
      effect of post-exercise body temperature changes on body composition results
      using ADP. SUBJECTS/METHODS: Forty young adults (18-30 years) participated in the
      study (23 females, 17 males). Resting heart rate was measured to calculate
      exercise intensity. First, an ADP test was done according to the instructions
      outlined by the manufacturer. Upon completion of the ADP test, the subject
      exercised on a treadmill at moderate intensity (~65% heart rate reserve) for 30 
      min to increase body temperature. Another ADP measurement followed the physical
      activity. Chamber temperature (CT) was measured during each of the trials using a
      thermistor to assess changes. Fat mass (FM), fat-free mass (FFM), percentage body
      fat (%BF) and CT were compared pre- and post exercise. RESULTS: Paired sample t
      tests revealed significant differences (P<0.05) between pre-exercise %BF and post
      exercise %BF (21.3 +/- 9.8% vs 19.6 +/- 10.2%), pre-exercise CT and post-exercise
      CT (22.7 +/- 1.2 vs 23.0 +/- 1.1  degrees C), and pre-exercise FM and post
      exercise FM (14.9 +/- 7.9 vs 13.8 +/- 8.0 kg). FFM showed no significant
      difference. CONCLUSION: This investigation demonstrates the importance of
      following the manufacturer's recommended pre-test protocol as the accuracy of the
      ADP testing may be compromised, resulting in lower FM and %BF estimations.

PMID- 23859995
TI  - Linear response of IGF-1 and FT3 to parenteral nutrition: results of an
      observational study.

PMID- 23859997
TI  - Delirium as a result of vitamin B12 deficiency in a vegetarian female patient.
AB  - Vitamin B12 deficiency can manifest with haematological, gastrointestinal and
      neuropsychiatric signs. The neuropsychiatric symptoms may be concurrent or
      precede the other symptoms. The reported case is a clinical case of delirium due
      to vitamin B12 deficiency in a female vegetarian patient. The patient was treated
      with vitamin B12 supplementation. Initially, it was difficult to diagnose this
      patient, who presented with delirium that could have been due to multiple causes.
      The finding underlines the importance of conducting a complete laboratory test
      panel for delirium, including the blood levels of vitamin B12. 

PMID- 23859996
TI  - Established dietary estimates of net acid production do not predict measured net
      acid excretion in patients with Type 2 diabetes on Paleolithic-Hunter-Gatherer
      type diets.
AB  - BACKGROUND/OBJECTIVES: Formulas developed to estimate diet-dependent net acid
      excretion (NAE) generally agree with measured values for typical Western diets.
      Whether they can also appropriately predict NAE for 'Paleolithic-type' (Paleo)
      diets-which contain very high amounts of fruits and vegetables (F&V) and
      concurrent high amounts of protein is unknown. Here, we compare measured NAEs
      with established NAE estimates in subjects with Type 2 diabetes (T2D).
      SUBJECTS/METHODS: Thirteen subjects with well-controlled T2D were randomized to
      either a Paleo or American Diabetes Association (ADA) diet for 14 days. Twenty
      four hour urine collections were performed at baseline and end of the diet
      period, and analyzed for titratable acid, bicarbonate and ammonium to calculate
      measured NAE. Three formulas for estimating NAE from dietary intake were used;
      two (NAE_diet R or L) that include dietary mineral intake and sulfate- and
      organic acid (OA) production, and one that is empirically derived (NAE_diet F)
      only considering potassium and protein intake. RESULTS: Measured NAE on the Paleo
      diet was significantly lower than on the ADA-diet (+31+/-22 vs 112+/-52 mEq/day,
      P=0.002). Although all formula estimates showed similar and reasonable
      correlations (r=0.52-0.76) with measured NAE, each one underestimated measured
      values. The formula with the best correlation did not contain an estimate of
      dietary OA production. CONCLUSIONS: Paleo-diets are lower in NAE than typical
      Western diets. However, commonly used formulas clearly underestimate NAE,
      especially for diets with very high F&V (as the Paleo diet), and in subjects with
      T2D. This may be due to an inappropriate estimation of proton loads stemming from
      OAs, underlining the necessity for improved measures of OA-related proton
      sources.

PMID- 23859998
TI  - Adiposity rebound is misclassified by BMI rebound.
AB  - BACKGROUND/OBJECTIVES: Adiposity rebound (AR) is defined as the nadir or the
      inflexion point of body mass index (BMI) percentiles between the age of 3 and 7
      years. An early rebound is seen as a risk of obesity and, thus, AR is considered
      as a suitable time period for prevention. As BMI does not reflect body
      composition, we aimed to examine the rebounds of fat mass index (FMI) and fat
      free mass index (FFMI) together with BMI. SUBJECTS/METHODS: Cross-sectional data
      of 19 264 children aged 3-11 years were pooled from three German studies (Kiel
      Obesity Prevention Study, the project 'Better diet. More exercise. KINDERLEICHT
      REGIONS' and regular examinations of Jena children). Height and weight were
      measured. Fat mass (FM) and fat-free mass (FFM) were obtained from bioelectrical
      impedance analysis and analysed using a population-specific algorithm.
      Percentiles of BMI, FMI and FFMI were constructed by the LMS method. RESULTS:
      Both BMI and FMI percentiles showed a rebound, whereas FFMI percentiles steadily
      increased with age. On P90, FMI rebound was about 1.6-1.8 years later compared
      with that of BMI, that is, at ages 4.2 years (BMI) and 5.8 years (FMI) in boys
      and at 4.2 years (BMI) and 6.0 years (FMI) in girls. At AR, the slope of the BMI
      P90 was explained by increases in FFMI rather than FMI. By contrast, at FMI
      rebound, the slope of BMI was strongly related to FMI. CONCLUSIONS: BMI rebound
      does not equal the rebound of FM. At AR, the slope in BMI is determined by the
      increase in FFMI. AR should be defined as FMI rebound rather than BMI rebound.

PMID- 23859999
TI  - Olive oil has a beneficial effect on impaired glucose regulation and other
      cardiometabolic risk factors. Di@bet.es study.
AB  - BACKGROUND: Despite the marked increase in cardiovascular risk factors in Spain
      in recent years, the prevalence and incidence of cardiovascular diseases have not
      risen as expected. Our objective is to examine the association between
      consumption of olive oil and the presence of cardiometabolic risk factors in the
      context of a large study representative of the Spanish population. SUBJECTS AND
      METHODS: A population-based, cross-sectional, cluster sampling study was
      conducted. The target population was the whole Spanish population. A total of
      4572 individuals aged >= 18 years in 100 clusters (health centers) were randomly
      selected with a probability proportional to population size. The main outcome
      measures were clinical and demographic structured survey, lifestyle survey,
      physical examination (weight, height, body mass index, waist, hip and blood
      pressure) and oral glucose tolerance test (OGTT) (75 g). RESULTS: Around 90% of
      the Spanish population use olive oil, at least for dressing, and slightly fewer
      for cooking or frying. The preference for olive oil is related to age,
      educational level, alcohol intake, body mass index and serum glucose, insulin and
      lipids. People who consume olive oil (vs sunflower oil) had a lower risk of
      obesity (odds ratio (OR)=0.62 (95% confidence interval (CI)=0.41-0.93, P=0.02)),
      impaired glucose regulation (OR=0.49 (95% CI=0.28-0.86, P=0.04)),
      hypertriglyceridemia (OR=0.53 (95% CI=0.33-0.84, P=0.03)) and low HDL cholesterol
      levels (OR=0.40 (95% CI=0.26-0.59, P=0.0001)). CONCLUSIONS: The results show that
      consumption of olive oil has a beneficial effect on different cardiovascular risk
      factors, particularly in the presence of obesity, impaired glucose tolerance or a
      sedentary lifestyle.

PMID- 23860001
TI  - The efficacy of protected mealtimes in reducing mealtime interruptions and
      improving mealtime assistance in adult inpatients in an Australian hospital.
AB  - BACKGROUND/OBJECTIVES: A Protected Mealtimes Programme (PMP) encourages staff,
      volunteers and visitors to assist patients and cease non-urgent clinical activity
      during mealtimes. Given the limited evidence available establishing the efficacy
      of PMP, we compared mealtime interruptions, mealtime assistance received and
      nutrient intakes before and after PMP implementation in adult inpatients on acute
      wards. SUBJECTS/METHODS: Data collected on patients at main meals before and
      after PMP implementation included the following: diet code, level of assistance
      required and received and by whom, time available to consume the meal, position
      of the patient and tray during eating, type of interruption and by whom and
      proportion of foods and drinks consumed. Outcomes pre- and post-PMP
      implementation were compared using chi(2), independent samples t-tests and
      logistic regression analyses. RESULTS: Over two years, 1632 inpatient mealtime
      observations were conducted (65 (18) years, 51% M). Similar proportions of
      patients received mealtime assistance when required (~84%, P=0.928). Feeding
      assistance nearly doubled post-PMP implementation (15-29%, P=0.002).
      Interruptions by nursing staff increased by 8% post-PMP implementation (P<0.001)
      and represented 61% of all interruptions. Interruptions were less likely to occur
      pre-PMP implementation (odds ratio, 0.403, 95% confidence interval, 0.301-0.539).
      Mealtime energy and protein intakes were not changed post-PMP (P=0.979, P=0.482,
      respectively). CONCLUSIONS: The PMP increased nursing staff availability at
      mealtimes and feeding assistance, but also increased mealtime interruptions. This
      may explain the lack of change in patient energy and protein consumption.
      Strategies promoting adherence with PMP implementation, such as nurse ward
      champions or nursing staff driving PMP implementation, may be required to
      maximise the benefits of protected mealtimes.

PMID- 23860000
TI  - Drinking water contributes to excessive iodine intake among children in Hebei,
      China.
AB  - BACKGROUND/OBJECTIVES: In Hebei province, China, over six million people are
      potentially exposed to excessive iodine through consumption of high iodine
      underground drinking water and consumption of iodized salt. The aim of this study
      is to evaluate the contributions of drinking water and iodized salt on children's
      iodine nutrition in one area of Hebei province in order to refine strategies to
      correct the excessive iodine intake in these areas. SUBJECTS/METHODS: To
      investigate the relationships between iodine content in water, iodized salt and
      urinary iodine content (UIC) in children (8-10 years), we randomly sampled three
      towns with a known median water iodine (MWI) of 150-300 MUg/l in Hengshui City,
      Hebei province and collected water, salt and urine samples. RESULTS: The median
      UIC was 518.1 MUg/l, the overall MWI was 247.0 MUg/l, and 83% of children sampled
      were found to have urinary iodine concentrations higher than the WHO criterion of
      300 MUg/l. There was a significant and positive correlation between the median
      UIC of the children and the MWI in the 12 villages where the children lived
      (Spearman R=0.79, P=0.002), but the UIC was not significantly correlated with the
      median salt intake (MSI) (Spearman R=-0.17, P=0.6). A multiple linear regression
      analysis indicated that 68.7% of the variability in median UIC is associated with
      variability in MWI in the 12 villages. CONCLUSIONS: Iodine in drinking water was
      identified to be the key contributor to this excessive iodine in children
      indicating that in these areas, intervention should focus on providing
      alternative drinking water supplies.

PMID- 23860002
TI  - Interactions of actinomyces -like organisms with host cells: light microscopic
      examination.
AB  - OBJECTIVE: To determine the interactions of Actinomyces-like organisms (ALOs)
      with host cells, including vaginal epithelial cells, polymorphonuclear leukocytes
      (PMNLs) and erythrocytes, using Pap smear microscopy and based on their light
      microscopic appearances. STUDY DESIGN: Cervicovaginal samples obtained from 200
      patients were examined by both Pap smear microscopy and anaerobic culturing.
      Since the results obtained by these methods were not concordant for diagnosis of
      genital Actinomyces, the results of Pap smear microscopy were used as a
      reference, and the smears with ALOs were carefully screened with regard to
      interactions of ALOs with host cells. RESULTS: ALOs were detected as attached to
      vaginal epithelial cells, PMNLs and erythrocytes via their filament-like
      structures. At some attachment sites, the epithelial cell membrane and filaments
      of ALOs were almost fused with each other. A group of PMNLs surrounded the ALOs.
      However, ALOs were observed to form colonies to evade phagocytosis by PMNLs. At
      the connection points between erythrocytes and ALOs, the findings of interest
      were the changes in the shapes of the erythrocytes and filament-like structures
      of the ALOs on the erythrocyte membrane. CONCLUSIONS: The adhesiveness of ALOs
      can be observed in routine Papanicolaou-stained cervicovaginal smears at light
      microscopic level.

PMID- 23860003
TI  - Achieving self-sufficiency of red blood cells based on universal voluntary blood
      donation in Latin America. The case of Nicaragua.
AB  - In 2007, the blood collection rate in Nicaragua was 106.6 units per 10,000
      inhabitants. Voluntary donation was 39%. The health authorities decided to pursue
      self sufficiency of blood by eliminating replacement donation and consolidating
      blood processing in two centers. Replacement donation was terminated in 2009,
      voluntary donation reached 100% in 2010, and the blood collection rate increased
      to 125.9 in 2011. The rate of red blood cell transfusion improved from 96.0 to
      119.1 units per 10,000 during the 4-year period. The political will of the
      government, pertinent technical leadership, and a country-wide approach were
      essential for attaining those goals. 

PMID- 23860004
TI  - COL4A1 mutation revealed by an isolated brain hemorrhage.

PMID- 23860005
TI  - A respiratory monitoring device based on clavicular motion.
AB  - Respiratory rate is one of the key vital signs yet unlike temperature, heart rate
      or blood pressure, there is no simple and low cost measurement device for medical
      use. Here we discuss the development of a respiratory sensor based upon
      clavicular motion and the findings of a pilot study comparing respiratory rate
      readings derived from clavicular and thoracic motion with an expiratory breath
      flow reference sensor. Simultaneously sampled data from resting volunteers (n =
      8) was analysed to determine the location of individual breaths in the data set
      and from these, breath periods and frequency were calculated. Clavicular sensor
      waveforms were found to be more consistent and of greater amplitude than those
      from the thoracic device, demonstrating good alignment with the reference
      waveform. On comparing breath by breath periods a close agreement was observed
      with the reference, with mean clavicular respiratory rate R(2) values of 0.89
      (lateral) and 0.98 (longitudinal-axis). This pilot study demonstrates the
      viability of clavicular respiratory sensing. The sensor is unobtrusive,
      unaffected by bioelectrical or electrode problems and easier to determine and
      more consistent than thoracic motion sensing. With relatively basic signal
      conditioning and processing requirements, it could provide an ideal platform for
      a low-cost respiratory monitor. 

PMID- 23860006
TI  - Validation of RiskCheck Bladder Cancer (c), version 5.0 for risk-adapted
      screening of bladder cancer.
AB  - INTRODUCTION: The aim of the study was to assess the strength of the online tool
      RiskCheck Bladder Cancer(c), version 5.0 (RCBC) for early detection of bladder
      cancer (BC). MATERIALS AND METHODS: RCBC was evaluated retrospectively based on
      the data of 241 patients, of which 141 were suffering from BC. Statistical
      analysis was performed by descriptive statistics, nonparametric group comparison,
      classification tree analysis and ROC analysis. RESULTS: ROC analysis of the risk
      classification showed a sensitivity of 71.6%, a specificity of 56.5%, a positive
      predictive value of 67.8%, a negative predictive value of 52% and an accuracy of
      63.5%. BC risk factors ranked by importance are time of smoking (p < 0.0001),
      gender (within the nonsmoking group: p < 0.009), occupational toxin exposure
      (within the group <35 years of smoking: p < 0.048) and amount of consumed
      cigarettes resulting in a 95% association with BC (within the group >35 years of
      smoking: p < 0.0001). CONCLUSIONS: The high predictive power of RCBC for the
      identification of asymptomatic patients living under risk could be demonstrated.

PMID- 23860008
TI  - Models and strategies in the development of antiobesity drugs.
AB  - Obesity is a leading cause of morbidity and mortality worldwide. There is still a
      wide disparity between the necessity and availability of safe and effective
      antiobesity pharmacotherapies. Current drugs are associated with adverse effects
      and are limited in their efficacy. There is thus an urgent need for new
      antiobesity agents. Animal models are critical to the study of the biological
      mechanisms underpinning energy homeostasis and obesity and provide useful tools
      for the development of novel antiobesity agents. Our understanding of the complex
      neuronal and hormonal systems that regulate appetite and body weight has largely
      been based on studies in animals. This review describes the physiological basis
      of appetite, rodent models used in the development of antiobesity drugs, and
      potential future targets for novel antiobesity agents.

PMID- 23860007
TI  - Erlotinib and radiation therapy for elderly patients with esophageal cancer -
      clinical and correlative results from a prospective multicenter phase 2 trial.
AB  - PURPOSE: Elderly patients with esophageal cancer who are not candidates for
      chemoradiation may benefit from targeted agents; hence erlotinib combined with
      radiotherapy was evaluated in this trial. MATERIALS AND METHODS: Patients >65
      years with carcinoma of the thoracic esophagus or gastroesophageal junction who
      were not eligible for platinum-based treatment received erlotinib daily for 1
      year starting on day 1 of radiotherapy [50.4 Gy days 1-28 (Mon-Fri) at 1.8 Gy per
      fraction]. Response was assessed by endoscopy and computed tomography. The
      primary endpoint was overall survival (OS), and secondary endpoints were complete
      response, progression-free survival (PFS) and toxicity. RESULTS: The ECOG
      performance status in the 17 study patients was 0,1 and 2 in 2, 12 and 3
      patients, respectively; 1, 5, 7 and 4 patients were in stage I, II, III and IV,
      respectively; adenocarcinoma was noted in 16 patients and squamous cell carcinoma
      in 1; there were 3 current, 12 past and 2 never smokers. Median OS was 7.3 months
      (95% confidence interval, CI: 3.8-22.3) with 14 deaths. There were 2 mucosal
      complete responses, 1 residual carcinoma in situ and 3 partial endoscopic
      responses in 9 patients who had endoscopy after radiotherapy. Estimated PFS was
      4.5 months (95% CI: 2.4-7.3). Progression was distant (n = 3), locoregional (n =
      6), unknown (n = 5) and too early (n = 3). Estimated 1-year survival was 29% (95%
      CI: 11-51%), 5 patients lived >12 months. Treatment-related toxicities of grade 3
      4 occurred in 5 patients. Patients with epidermal growth factor receptor
      amplification and never smokers had the longest OS (22.3 and 16.6 months,
      respectively). CONCLUSIONS: Erlotinib with radiotherapy is tolerable and warrants
      further biomarker-driven evaluation in this population.

PMID- 23860009
TI  - Visual outcomes and patient satisfaction in 9366 eyes using a refractive
      segmented multifocal intraocular lens.
AB  - PURPOSE: To report the effectiveness, patient satisfaction, and complication rate
      with a zonal refractive intraocular lens (IOL) in a high volume of patients.
      SETTING: Private clinic, London, United Kingdom. DESIGN: Case series. METHODS:
      Retrospective data of patients with binocular Lentis Mplus IOLs were analyzed.
      The main outcome measures were uncorrected distance visual acuity (UDVA),
      uncorrected near visual acuity (UNVA), corrected distance visual acuity, manifest
      refraction, patient satisfaction, and complications. One-month, 3-month, and 6
      month data were analyzed. RESULTS: The study comprised 9366 eyes of 4683
      patients. The mean spherical equivalent changed from +1.73 diopters (D) +/- 3.37
      (SD) preoperatively to -0.02 +/- 0.60 D at 3 months and +0.03 +/- 0.60 D at 6
      months. Ninety-five percent of patients achieved a binocular UDVA of 6/7.5 (0.1
      logMAR) or better 3 months postoperatively. The mean binocular UNVA was 0.155 +/-
      0.144 logMAR and 0.159 +/- 0.143 logMAR at 3 months and 6 months, respectively.
      Severe dysphotopsia requiring an IOL exchange occurred in 55 eyes. Patient
      satisfaction was high, with 97.5% of patients willing to recommend the procedure.
      CONCLUSIONS: The zonal refractive IOL provided excellent distance and near visual
      acuity. The postoperative complication rate was clinically acceptable, and
      patient satisfaction high. FINANCIAL DISCLOSURE: Dr. Schallhorn is a consultant
      to Abbott Medical Optics, Inc. No author has a financial or proprietary interest
      in any material or method mentioned.

PMID- 23860010
TI  - Repeatability, reproducibility, and agreement of corneal power measurements
      obtained with a new corneal topographer.
AB  - PURPOSE: To study the repeatability and reproducibility of corneal power
      measurements obtained with a new corneal topographer (Keratograph 4) and assess
      their agreement with those obtained by a rotating Scheimpflug camera (Pentacam
      HR) and an automated keratometer (IOLMaster). SETTING: Eye Hospital, Wenzhou
      Medical University, Wenzhou, China. DESIGN: Observational cross-sectional study.
      METHODS: One eye of normal subjects was measured 3 times using all devices.
      Another operator performed an additional 3 consecutive scans using the corneal
      topographer. One week later, the first operator repeated the corneal power
      measurements using the corneal topographer. Parameters were flat meridian power,
      steep meridian power, average power, J0, and J45. The repeatability and
      reproducibility of measurements were assessed by the within-subject standard
      deviation (Sw), repeatability (2.77 Sw), coefficient of variation (CoV), and
      intraclass correlation coefficient (ICC). Agreement between devices was assessed
      using 95% limits of agreement (LoA). RESULTS: Intraoperator repeatability and
      interoperator and intersession reproducibility of all measured parameters showed
      a CoV of less than 0.3%, a 2.77 Sw of 0.32 diopter or less, and an ICC of more
      than 0.97. No significant differences in the parameters were noted between the
      corneal topographer and Scheimpflug camera. Statistically significant differences
      existed between the parameters analyzed by the corneal topographer and the
      automated keratometer, except J45. The mean differences between the corneal
      topographer and the other 2 devices were small, and the 95% LoA were narrow for
      all measurements. CONCLUSION: The new corneal topographer had excellent
      reliability and high agreement with the other 2 devices in corneal power
      measurements in normal subjects. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 23860011
TI  - Clinical results of using a high-repetition-rate excimer laser with an optimized
      ablation profile for myopic correction in 10 235 eyes.
AB  - PURPOSE: To evaluate the visual outcomes, safety, stability, efficacy, and
      predictability of laser in situ keratomileusis (LASIK) to correct myopia using a
      high-repetition-rate excimer laser with an optimized ablation profile. SETTING:
      Private clinic, Tokyo, Japan. DESIGN: Retrospective noncomparative study.
      METHODS: In this study, patients had LASIK using the Schwind Amaris excimer laser
      for myopic correction. RESULTS: The study comprised 10  235 eyes of 5191
      patients. The patients' mean age was 33.9 years +/- 7.84 (SD) (range 18 to 56
      years). The mean preoperative manifest refraction spherical equivalent (MRSE) was
      -5.02 +/- 2.17 diopters (D) (range -2.75 to -11.50 D). Three months
      postoperatively, 82.0% of patients achieved an uncorrected distance visual acuity
      of -0.18 logMAR or better and 96.9% achieved 0.00 logMAR or better. The MRSE was
      within +/-0.50 D of the intended refractive target in 88.4% of eyes and within +/
      1.00 D in 98.8%. Despite using the profile designed to minimize postoperative
      aberrations, the postoperative corneal and ocular higher-order aberrations
      increased. CONCLUSION: Laser in situ keratomileusis using a high-repetition-rate
      excimer laser was a safe and effective procedure, yielding predictable results
      for a wide range of myopic patients. FINANCIAL DISCLOSURE: Mr. Magnago is an
      employee of Schwind Eye-Tech Solutions GmbH & Co. KG. No other author has a
      financial or proprietary interest in any material or method mentioned.

PMID- 23860012
TI  - Comparison of intraocular lens power calculation methods after myopic laser
      refractive surgery without previous refractive surgery data.
AB  - PURPOSE: To compare the accuracy of intraocular lens (IOL) power calculation
      methods for post-myopic excimer laser surgery patients without previous
      refractive surgery data using the Holladay IOL Consultant Program and the
      American Society of Cataract and Refractive Surgery (ASCRS) IOL Power Calculator.
      SETTING: Wang Vision Cataract and LASIK Center, Nashville, Tennessee, USA.
      DESIGN: Case series. METHODS: Eight methods were used to calculate IOL power:
      Holladay 2 partial coherence interferometry (PCI)-K, Holladay 2 FlatK, Wang-Koch
      Maloney, Shammas No-History, Haigis-L, ASCRS-Average, ASCRS-Min, and ASCRS-Max.
      The optimum IOL power corresponding to the target refraction was back-calculated
      using the stable post-cataract surgery refraction and implanted IOL power. Using
      the optimum IOL power, the predicted IOL power error and the resultant refractive
      error with each method were calculated and compared. RESULTS: The Holladay 2
      FlatK method was most accurate for IOL power calculation, followed by the
      Holladay 2 PCI-K, ASCRS-Min, Wang-Koch-Maloney, ASCRS-Average, Shammas No
      History, Haigis-L, and ASCRS-Max. Statistically significant differences were
      observed between Holladay 2 FlatK and Holladay 2 PCI-K (P<.05), Wang-Koch-Maloney
      and ASCRS-Average (P<.05), and Haigis-L and ASCRS-Max (P<.01). No statistically
      significant differences were observed between the Holladay 2 PCI-K, ASCRS-Min,
      and Wang-Koch-Maloney or between the ASCRS-Average, Shammas No-History, and
      Haigis-L (both P>.05). CONCLUSIONS: The Holladay 2 FlatK method provided the most
      accurate IOL power in eyes without previous myopic laser surgery data. If the
      Holladay IOL Consultant Program is unavailable, the ASCRS methods can be used;
      the ASCRS-Min represents the most accurate method.

PMID- 23860014
TI  - Correlative analysis of social support with anxiety and depression in men
      undergoing in vitro fertilization embryo transfer for the first time.
AB  - OBJECTIVE: To explore the correlation between the level of social support and the
      extent of anxiety and depression in Chinese men undergoing in vitro fertilization
      embryo transfer (IVF-ET) for the first time, in order to provide a basis for male
      mental health counselling. METHODS: Self-administered questionnaires covering
      general health status, anxiety (self-rating anxiety scale), depression (self
      rating depression scale) and social support (social support rating scale) were
      completed by men undergoing their first round of IVF-ET. RESULTS: A total of 502
      completed questionnaires were considered valid and were analysed. The anxiety,
      depression and social support scores for men undergoing their first round of IVF
      ET were significantly higher than those for Chinese normative data. Social
      support was inversely correlated with anxiety and depression. CONCLUSIONS: These
      findings suggest that health care professionals should provide specific
      psychological counselling to Chinese men undergoing their first round of IVF-ET,
      in order to improve their psychological health and to facilitate increased levels
      of social support.

PMID- 23860013
TI  - The antimicrobial agent C31G is effective for therapy for HSV-1 ocular keratitis
      in the rabbit eye model.
AB  - The amphoteric C31G solution contains equimolar alkyl dimethlyglycine and alkyl
      dimethyl amine oxide buffered with citric acid. C31G acts as a broad spectrum
      antiviral and an antibacterial. No previous in vivo studies have been done to
      test C31G in an animal model of HSV-1 ocular keratitis. We assessed the anti
      herpetic activity of C31G in the rabbit eye model using three treatment groups:
      (1) 1% trifluorothymidine (TFT); (2) 0.25% C31G plus 0.5% hydroxypropyl
      methylcellulose (HPMC); and (3) vehicle, 0.5% HPMC. Scarified rabbit corneas were
      inoculated with the HSV-1 strain McKrae. On post inoculation (PI) day 3, rabbits
      were placed in three balanced groups based on slit-lamp examination (SLE) scores.
      Treatment began on PI day 3, five times a day for five consecutive days. In
      addition to the daily, masked SLE scoring, the eyes were assessed daily for
      stromal opacity, scleral inflammation, neovascularization, eyelid inflammation,
      inflammatory discharge, and epiphora. C31G and TFT were very effective in
      reducing the lesions and pathogenesis associated with HSV-1 ocular keratitis. The
      vehicle control scores were significantly higher and did not effectively treat
      HSV-1 keratitis. C31G has the potential to be used to treat herpetic keratitis as
      well as other herpetic topical lesions in humans. 

PMID- 23860015
TI  - Reliability and validity of a self-reported measure of medication adherence in
      patients with type 2 diabetes mellitus in Korea.
AB  - OBJECTIVE: This study examined the psychometric properties of the Korean version
      of the eight-item Morisky Medication Adherence Scale (MMAS-8) to measure
      adherence to diabetes medication in patients with type 2 diabetes mellitus.
      METHODS: The English version of the MMAS-8 was translated into Korean and
      administered to patient with type 2 diabetes mellitus via face-to-face
      interviews, conducted by an independent interviewer. Patient characteristics and
      glycosylated haemoglobin (HbA1c) levels were assessed at the same clinic visit. A
      proportion of patients was randomly selected for 2-week test-retest reliability
      via telephone interviews. Convergent validity of the MMAS-8 against a four-item
      MMAS, correlations with HbA1c levels and construct validity of the MMAS-8 were
      evaluated. RESULTS: In total, 317 patients were included; 70 completed the 2-week
      test-retest interview. Internal consistency reliability was moderate and test
      retest reliability of the MMAS-8 was excellent, although a ceiling effect was
      detected. Good convergent validity was shown by the high correlation of the new
      scale scores with the original MMAS-4. A significant association was found
      between MMAS-8 scores and HbA1c levels. Using glycaemic control as a gold
      standard, sensitivity was 74.1% and specificity was 38.3%. Explanatory factor
      analysis identified three dimensions of the scale. CONCLUSIONS: In light of
      acceptable reliability and validity, the MMAS-8 is a simple and quick method for
      the assessment of medication adherence among patient with type 2 diabetes
      mellitus, in a busy clinic setting.

PMID- 23860016
TI  - Association of angiotensinogen gene polymorphisms and angiogenic factors with
      preeclampsia in Chinese women.
AB  - OBJECTIVE: To investigate the association of angiotensinogen (AGT) gene
      polymorphisms and angiogenic factors with preeclampsia (PE) in Chinese women.
      METHODS: A study on Chinese women was performed. Detection of the M235T
      polymorphism of AGT gene was carried out by PCR. Using a chi2 test, genotype and
      allele frequencies were compared in all groups. Maternal serum levels of vascular
      endothelial growth factor (VEGF) and placental growth factor (PlGF) and soluble
      fms-like tyrosine kinase 1 (sFlt1) at gestation were compared between 92 women
      with PE and 100 controls by ELISA. RESULTS: Compared to the controls, the AGT
      homozygous of TT genotype in PE occurred significantly more frequently and the T
      allele was observed to occur more frequently than the M allele (p < 0.05). sFlt1
      was present in high quantities in the serum of women with PE and was associated
      with low levels of free VEGF and PlGF (p < 0.05). Plasma sFlt1 levels are higher
      in PE patients with TT heterozygotes compared with MM homozygotes, but PIGF is
      lower (p < 0.05). Plasma VEGF concentrations showed no significant difference.
      CONCLUSIONS: Our study showed that AGT M235T polymorphism is associated with PE
      in Chinese women. Furthermore, the gene polymorphism of the components of the
      renin-angiotensin system may contribute to the concentration alterations of
      sFlt1, VEGF, and PlGF in maternal serum, which causes disordered vasculogenesis
      contributing to PE.

PMID- 23860017
TI  - Imaging local sphingomyelin-rich domains in the plasma membrane using specific
      probes and advanced microscopy.
AB  - Sphingomyelin (SM) is one of the major lipids in the mammalian plasma membrane.
      Multiple lines of evidence suggest that SM plays at least two functional roles in
      the cell, as a reservoir of lipid second messengers and as a platform for
      signaling molecules. To understand the molecular organization and dynamics of the
      SM-rich membrane domains, new approaches have been developed utilizing newly
      characterized specific SM-binding probes and state-of-the-art microscopy
      techniques. The toxic protein from the sea anemone, equinatoxin II, has been
      characterized as a specific probe for SM. The cytolytic protein from the
      earthworm, lysenin, has also been used as a SM-specific probe for the analysis of
      the heterogeneity of SM-rich membrane domains. Recently, using a non-toxic form
      of lysenin, we showed the spatial and temporal localization of SM in the plasma
      membrane by confocal and super-resolution microscopy. New microscopy techniques
      have also been introduced by other groups to help visualize membrane lipid
      domains. Here we review the most recent studies on imaging the SM-rich domains in
      biological membranes. This article is part of a Special Issue entitled New
      Frontiers in Sphingolipid Biology. 

PMID- 23860018
TI  - Science-based yoga - stretching mind, body, and soul.

PMID- 23860019
TI  - Professional kinesiology practice for chronic low back pain: single-blind,
      randomised controlled pilot study.
AB  - BACKGROUND: Chronic low back pain is a highly prevalent condition with no
      definitive treatment. Professional Kinesiology Practice (PKP) is a little known
      complementary medicine technique using non-standard muscle testing; no previous
      effectiveness studies have been performed. METHODS: This is an exploratory,
      pragmatic single-blind, 3-arm randomised sham-controlled pilot study with waiting
      list control (WLC) in private practice UK (2007-2009). 70 participants scoring
      >=4 on the Roland and Morris Disability Questionnaire (RMDQ) were randomised to
      real or sham PKP receiving 1 treatment weekly for 5 weeks or a WLC. WLC's were re
      randomised to real or sham after 6 weeks. The main outcome was a change in RMDQ
      from baseline to end of 5 weeks of real or sham PKP. RESULTS: With an effect size
      of 0.7 real treatment was significantly different to sham (mean difference RMDQ
      score = -2.9, p = 0.04, 95% CI -5.8 to -0.1). Compared to WLC, real and sham
      groups had significant RMDQ improvements (real -9.0, p < 0.01, 95% CI -12.1 to 
      5.8; effect size 2.1; sham -6.1, p < 0.01, 95% CI -9.1 to -3.1; effect size 1.4).
      Practitioner empathy (CARE) and patient enablement (PEI) did not predict outcome;
      holistic health beliefs (CAMBI) did, though. The sham treatment appeared
      credible; patients did not guess treatment allocation. 3 patients reported minor
      adverse reactions. CONCLUSIONS: Real treatment was significantly different from
      sham demonstrating a moderate specific effect of PKP; both were better than WLC
      indicating a substantial non-specific and contextual treatment effect. A larger
      definitive study would be appropriate with nested qualitative work to help
      understand the mechanisms involved in PKP.

PMID- 23860020
TI  - Efficacy of a novel herbal multicomponent traditional Chinese medicine therapy
      approach in patients with atopic dermatitis.
AB  - BACKGROUND: In Western medicine, the application of topical steroids and oral
      antihistaminic or antiallergic agents is the main treatment option for atopic
      dermatitis (AD). However, instead of these therapies the disease may remain
      intractable in some patients, resulting in long-term exposure to these chemical
      agents and consequently leading to concerns about possible adverse drug
      reactions. METHODS: In the present open-label clinical study, the efficacy and
      safety of a novel multi component TCM therapy approach for AD was investigated.
      Therefore, 94 patients received the formula I (10 crude drugs) orally, combined
      with both the lotion II (7 crude drugs), and the ointment III (8 crude drugs).
      Each crude drug was extracted with boiling water in a defined manner,
      concentrated, and reworked into the preparations. Standardized scores were used
      for evaluating the severities of AD (clinical severity 0-4) and pruritus
      (pruritus score 0-4). RESULTS: Both scores had significantly improved at the end
      of a 12 month treatment (P<0.001). Eosinophil ratio and serum IgE levels, which
      were elevated in AD patients, were significantly reduced at the end of therapy
      (P<0.01). In 32 of 94 treated patients the condition markedly improved, in 59
      cases AD improved, and in 3 patients there was a slight improvement with no case
      of ineffective treatment. There was no hint of renal or hepatic toxicity or any
      other adverse effects. CONCLUSION: The present study confirms that the 3 newly
      developed herbal TCM combination preparations are clinically efficacious on AD,
      accomplishing a significant reduction in both clinical and pruritus scores as
      well as in eosinophil ratios and serum IgE levels.

PMID- 23860021
TI  - Relationship between adiponectin and leptin, and blood lipids in hyperlipidemia
      patients treated with red yeast rice.
AB  - BACKGROUND: This study aimed to investigate the possible relationships between
      adiponectin and leptin, blood lipids such as total cholesterol, high-density
      lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and
      triglycerides (TG) as well as other clinical biomarkers in hyperlipidemia
      patients treated with red yeast rice. METHODS: 30 patients with primary
      hyperlipidemia were recruited, treated with red rice yeast capsules 600 mg twice
      a day for 8 weeks, and followed up for 4 weeks. The primary endpoint was the mean
      difference in LDL-C from baseline to week 8, while the secondary endpoints were
      the mean percentage changes from baseline of total cholesterol, TG, HDL-C,
      adiponectin, and leptin. RESULTS: At week 8, the decrease in LDL-C and total
      cholesterol was -38.11 +/- 30.90 mg/dl (p < 0.0001) and -44.54 +/- 27.46 mg/dl (p
      < 0.0001), respectively, and the increase in adiponectin was 35.83 +/- 67.85
      MUg/ml (p = 0.017) as compared to baseline. Adiponectin also correlated
      positively with HDL-C (r2 = 0.39; p = 0.001). Serum leptin correlated negatively
      with TG (r2 = 0.19; p = 0.035), and there was a trend of correlation between
      leptin and HDL-C, but this was not statistically significant (r2 = 0.16; p =
      0.052). CONCLUSION: Red yeast rice can significantly increase adiponectin and can
      significantly lower LDL-C and total cholesterol levels. Adiponectin correlates
      positively with HDL-C while serum leptin correlates negatively with TG. Red yeast
      rice has a potentially protective effect in obesity-related and cardiovascular
      diseases.

PMID- 23860022
TI  - The treatment experience questionnaire: development and validation of a
      questionnaire assessing the individual's emotional, perceptual, and cognitive
      reactions to alternative, physical, and dental treatments.
AB  - BACKGROUND: The aim of this study was to develop and validate a questionnaire
      designed to assess the patient's affective, cognitive, and perceptual state
      during treatment administration. METHODS: 362 individuals (214 females, 148
      males, mean age 54.6 years) with predominantly musculoskeletal or dental problems
      participated in the study. Patients responded to the questionnaire immediately
      following a treatment. The questionnaire included items of 9 proposed scales
      devised to assess mood, psychological tension, sleepiness, mental absorption,
      treatment appraisal, perceived cooperation during treatment administration,
      perceived somatosensory intensity of treatment as well as negative and positive
      bodily sensations during treatment. Treatments were administered in 2 spa
      centers, a clinic for physical medicine and rehabilitation and a clinic for
      dentistry. Treatments investigated were among others dental treatment, massage,
      packs, baths, relaxation training, exercise, and acupuncture. RESULTS: The
      proposed scales were confirmed. Scales had adequate to good reliability and
      validity. All scales significantly distinguished between treatments. CONCLUSION:
      The devised questionnaire has adequate properties to assess patients' experiences
      during treatment administration.

PMID- 23860023
TI  - [Clinical aspects of phytosterols in human nutrition].
AB  - The research focuses on effective supply of phytosterols in human nutrition.
      Their beneficial influence concerning the lowering effect on the concentration of
      LDL cholesterol is underlined and the occurring changes in serum concentrations
      of the fractions related to cholesterol absorption and synthesis are pointed out.
      It seems that the use of phytosterols in human nutrition may be the factor
      playing an important role in preventing the development of dyslipidemia.

PMID- 23860024
TI  - Naturopathic reflex therapies for the treatment of chronic back and neck pain -
      Part 1: Neurobiological foundations.
AB  - Evidence from recent RCT's has shown that naturopathic reflex therapies such as
      massage, Gua Sha massage, cupping, wet packs, or rhythmic embrocation etc. are
      helpful in reducing symptoms of chronic pain. These bodily oriented therapies are
      likely able to influence chronic pain not only through brain mechanisms such as
      expectation or the feeling of well-being, but also through mechanisms at the
      level of the peripheral nociceptor and the spinal cord. However, the
      neurobiological basis of these effects has rarely been investigated even though
      the accumulating knowledge of the pathophysiology of chronic pain syndromes
      allows for developing specific hypotheses. This essay discusses specific reflex
      therapies (cupping, Gua Sha massage, classical massage, and rhythmic embrocation)
      and their possible mechanisms of action via ascending pathways to the brain.

PMID- 23860025
TI  - Naturopathic reflex therapies for the treatment of chronic pain - Part 2:
      Quantitative sensory testing as a translational tool.
AB  - Naturopathic reflex therapies such as massage, Gua Sha massage, cupping, wet
      packs etc. are likely able to influence chronic pain at different levels of the
      nociceptive system. Since naturopathic reflex therapies have been shown to reduce
      symptoms of chronic pain and often utilize intense manipulation of the
      environment of the nociceptor (e.g. Gua Sha massage or cupping), it can be
      hypothesized that they unfold part of their effect at the level of the peripheral
      nociceptor and the spinal cord. However, these hypotheses have to date not been
      tested systematically. Standardized sensory testing, e.g., as performed by
      'quantitative sensory testing' (QST), a comprehensive battery of tests for
      clinical trials, may offer additional information about the mechanisms of
      naturopathic reflex therapies since it provides a measure for the mechanisms of
      nociceptive pain on all levels of the pain processing system. This method paper
      describes the potential role of QST in research on the neurobiological mechanisms
      of naturopathic reflex therapies.

PMID- 23860026
TI  - Electroporation as a method to induce myofiber regeneration and increase the
      engraftment of myogenic cells in skeletal muscles of primates.
AB  - Engraftment of intramuscularly transplanted myogenic cells in mice can be
      optimized after induction of massive myofiber damage that triggers myofiber
      regeneration and recruitment of grafted cells; this generally involves either
      myotoxin injection or cryodamage. There are no effective methods to produce a
      similar process in the muscles of large mammals such as primates. In this study,
      we tested the use of intramuscular electroporation for this purpose in 11
      macaques. The test sites were 1 cm of skeletal muscle. Each site was treated with
      3 penetrations of a 2-needle electrode with 1 cm spacing, applying 3 pulses of
      400 V/cm, for a duration of 5 milliseconds and a delay of 200 milliseconds during
      each penetration. Transplantation of beta-galactosidase-labeled myoblasts was
      done in electroporated and nonelectroporated sites. Electroporation induced
      massive myofiber necrosis that was followed by efficient muscle regeneration.
      Myoblast engraftment was substantially increased in electroporated compared with
      nonelectroporated sites. This suggests that electroporation may be a useful tool
      to study muscle regeneration in primates and other large mammals and as a method
      for increasing the engraftment of myoblasts and other myogenic cells in
      intramuscular transplantation. 

PMID- 23860027
TI  - Amyloid-beta inhibits thrombospondin 1 release from cultured astrocytes: effects
      on synaptic protein expression.
AB  - Among the consequences of Alzheimer disease are disturbances in synaptic
      integrity that ultimately lead to impaired cognitive functions. Thrombospondins
      are extracellular matrix proteins that, in the CNS, are predominantly produced by
      astrocytes and have been implicated in synaptogenesis. This study examined the
      effects of amyloid-beta (Abeta(1-42); Abeta) peptide on intracellular and
      extracellular levels of thrombospondin 1 (TSP-1) in cultured astrocytes. Amyloid
      beta caused a significant (1- to 3-fold) increase in astrocytic intracellular
      levels of TSP-1 (increased retention) that was associated with a reduction of its
      release from astrocytes. Because Abeta is known to induce oxidative stress in
      astrocytes, we examined the effects of the antioxidants tempol and apocynin on
      astrocytic TSP-1 levels and release. Treatment of Abeta-exposed astrocyte
      cultures with antioxidants significantly diminished its cellular retention and
      stimulated its release. Furthermore, the addition of conditioned media derived
      from Abeta-treated cultured astrocytes that contained a reduced TSP-1 content
      resulted in a significant loss of synaptophysin and PSD95 in cultured neurons.
      These findings suggest that Abeta-mediated reduction in astrocytic TSP-1 release,
      possibly related to oxidative stress, contributes to the loss of synaptophysin in
      neurons. Strategies aimed at enhancing the astrocytic release of TSP-1 may have a
      therapeutic benefit in Alzheimer disease.

PMID- 23860028
TI  - Calcium influx and calpain activation mediate preclinical retinal
      neurodegeneration in autoimmune optic neuritis.
AB  - Optic neuritis is a common manifestation of multiple sclerosis, an inflammatory
      demyelinating disease of the CNS. Recently, the neurodegenerative component of
      multiple sclerosis has come under focus particularly because permanent disability
      in patients correlates well with neurodegeneration; and observations in both
      humans and multiple sclerosis animal models highlight neurodegeneration of
      retinal ganglion cells as an early event. After myelin oligodendrocyte
      glycoprotein immunization of Brown Norway rats, significant retinal ganglion cell
      loss precedes the onset of pathologically defined autoimmune optic neuritis. To
      study the role calcium and calpain activation may play in mediating early
      degeneration, manganese-enhanced magnetic resonance imaging was used to monitor
      preclinical calcium elevations in the retina and optic nerve of myelin
      oligodendrocyte glycoprotein-immunized Brown Norway rats. Calcium elevation
      correlated with an increase in calpain activation during the induction phase of
      optic neuritis, as revealed by increased calpain-specific cleavage of spectrin.
      The relevance of early calpain activation to neurodegeneration during disease
      induction was addressed by performing treatment studies with the calpain
      inhibitor calpeptin. Treatment not only reduced calpain activity but also
      protected retinal ganglion cells from preclinical degeneration. These data
      indicate that elevation of retinal calcium levels and calpain activation are
      early events in autoimmune optic neuritis, providing a potential therapeutic
      target for neuroprotection. 

PMID- 23860029
TI  - Filtration of protein aggregates increases the accuracy for diagnosing prion
      diseases in brain biopsies.
AB  - In brain biopsies taken from patients with rapidly progressive dementia, the
      first differential diagnoses to be ruled out are prion diseases. For safe
      diagnostic processing of tissue and instruments, a rapid, highly sensitive, and
      specific analysis for prion aggregates is necessary. Here, we examined 16 brain
      biopsies and brain samples (frontal cortex and cerebellum) from 65 autopsies by
      Western blot, paraffin-embedded tissue (PET) blot, immunohistochemistry, and the
      recently described membrane adsorption assay (MAA) for their suitability to
      detect pathologic prion protein. In our hands, the PET blot method provided the
      highest sensitivity in prion detection (biopsies, 100%; all autopsy sections,
      96.3%), closely followed by the MAA (biopsies, 100%; all autopsy samples, 96%)
      and Western blot analysis (biopsies, 100%; all autopsy samples, 92%).
      Conventional immunohistochemistry is the least sensitive method (biopsies, 50%;
      all autopsy sections, 80%) and also gave 1 false-positive biopsy result.
      Consequently, our standard diagnostic protocol is to use the MAA as a first step
      for detecting or excluding a prion disease, followed by the PET blot for the
      prion deposition pattern, Western blotting for prion typing, and
      immunohistochemistry for differential diagnoses. With this standard and the
      availability of unfixed tissue, a diagnosis was possible in all 16 biopsies
      examined. 

PMID- 23860030
TI  - Diffuse traumatic axonal injury in the optic nerve does not elicit retinal
      ganglion cell loss.
AB  - Much of the morbidity after traumatic brain injury (TBI) is associated with
      traumatic axonal injury (TAI). Although most TAI studies focus on corpus callosum
      white matter, the visual system has received increased interest. To assess visual
      system TAI, we developed a mouse model of optic nerve TAI. It is unknown,
      however, whether this TAI causes retinal ganglion cell (RGC) death. To address
      this issue, YFP (yellow fluorescent protein)-16 transgenic mice were subjected to
      mild TBI and followed from 2 to 28 days. Neither TUNEL (terminal deoxynucleotidyl
      transferase dUTP nick end labeling)-positive or cleaved caspase-3-immunoreactive
      RGCs were observed from 2 to 28 days after TBI. Quantification of
      immunoreactivity of Brn3a, an RGC marker, demonstrated no RGC loss; parallel
      electron microscopic analysis confirmed RGC viability. Persistent RGC survival
      was also consistent with the finding of reorganization in the proximal axonal
      segments after TAI, wherein microglia/macrophages remained inactive. In contrast,
      activated microglia/macrophages closely enveloped the distal disconnected,
      degenerating axonal segments at 7 to 28 days after injury, thereby confirming
      that this model consistently evoked TAI followed by disconnection. Collectively,
      these data provide novel insight into the evolving pathobiology associated with
      TAI that will form a foundation for future studies exploring TAI therapy and its
      downstream consequences. 

PMID- 23860032
TI  - Rd8 mutation in the Crb1 gene of CD11c-eYFP transgenic reporter mice results in
      abnormal numbers of CD11c-positive cells in the retina.
AB  - There has been considerable debate about whether dendritic cells (DCs), which are
      potent antigen-presenting cells pivotal to adaptive immune responses, are present
      in CNS parenchyma. In studies aimed at answering this issue, we discovered that
      while the neural retina of young naive transgenic C57BL/6 CD11c-eYFP reporter
      mice contained more than 800 CD11c-positive cells/retina, these cells were
      virtually absent in C57BL/6 CD11c-DTR/GFP mice. Clinical fundus examination,
      confocal imaging of retinal whole mounts, and sections revealed colocalization of
      CD11c-positive cells with classic mild to severe retinal dystrophic lesions.
      Immunophenotypic analysis revealed that CD11c-positive cells in the neural retina
      of these mice had the characteristic profile of activated microglia and not DCs.
      Genotypic analysis confirmed that the cause of the retinal dystrophic lesions in
      CD11c-eYFP transgenic mice was the occurrence of the Crb1(rd8) mutation, which
      affects all mice of the C57BL/6N strain but not the C57BL/6J strain. Comparison
      of 2 different types of CD11c reporter transgenic mice revealed that a mutation
      in the Crb1 gene leads to retinal degeneration resulting in the activation of
      large numbers of local microglia that could be readily mistaken for CD11c
      positive putative DCs.

PMID- 23860031
TI  - MicroRNAs in cerebral ischemia-induced neurogenesis.
AB  - Cerebral ischemia induces neurogenesis, including proliferation and
      differentiation of neural progenitor cells and migration of newly generated
      neuroblasts. MicroRNAs (miRNAs) are small noncoding RNAs that decrease gene
      expression through mRNA destabilization and/or translational repression. Emerging
      data indicate that miRNAs have a role in mediating processes of proliferation and
      differentiation of adult neural progenitor cells. This article reviews recent
      findings on miRNA profile changes in neural progenitor cells after cerebral
      infarction and the contributions of miRNAs to their ischemia-induced
      proliferation and differentiation. We highlight interactions between the miR-124
      and the miR17-92 cluster and the Notch and Sonic hedgehog signaling pathways in
      mediating stroke-induced neurogenesis. 

PMID- 23860034
TI  - Rehydration of Air-Dried Smears versus Wet Fixation: A Cross-Sectional Study.
AB  - BACKGROUND: The Papanicolaou (Pap) smear is an effective method for early
      detection of cervical cancer. The routine practice of staining is to immediately
      fix the cervical smear in 95% ethyl alcohol. An alternative method of rehydrating
      the air-dried cervical smears followed by fixation and conventional staining
      method can overcome most of the problems associated with short supply and storage
      of alcohol, wet fixing of slides and transporting them to the cytology centre if
      the Pap smears are prepared at a peripheral centre. There are only few studies
      regarding rehydration of cervical smears as a substitute for wet fixation. AIM:
      The current study was undertaken to assess this technique as an alternative
      method for conventional wet-fixed smears. MATERIAL AND METHODS: This study was
      done over a period of 15 months in a tertiary care setup. Two sets of 461
      cervical smears were examined; the smears in the first set were fixed in 95%
      ethyl alcohol and the other set of 461 smears was air dried, rehydrated and then
      fixed in 95% ethyl alcohol. Both the smears were stained with Pap stain, examined
      for preservation of cytomorphological features and evaluated using the
      modification of parameters given by Ng et al. [Acta Cytologica 1994;38:56-64].
      RESULTS AND ANALYSIS: Two sets of 461 smears each, one air dried and rehydrated
      and the other wet fixed in alcohol, were evaluated for cytomorphological
      preservation, and comparison was done. In wet-fixed smears, morphology was
      excellent in the majority of cases (80.7%). Cytomorphology was optimal in 18% and
      suboptimal in 1.3% of the cases. The air-dried and rehydrated smears showed
      excellent morphological preservation in 67%, followed by 29.9% optimal and 2.8%
      suboptimal preservation. The p value was >0.05, which was not significant.
      CONCLUSION: Rehydration, followed by fixation of air-dried smears, is a simple,
      feasible, applicable and reliable fixation technique which is comparable to the
      wet-fixed conventional technique used for cervical smears and can be applied for
      evaluation on a routine basis.

PMID- 23860035
TI  - Glucose utilization, lipid metabolism and BMP-Smad signaling pathway of porcine
      intramuscular preadipocytes compared with subcutaneous preadipocytes.
AB  - BACKGROUND/AIMS: We previously reported that porcine intramuscular (i.m.)
      preadipocytes were different from subcutaneous (s.c.) preadipocytes on cell
      differentiation and lipid accumulation, but the underlying mechanisms remained
      unknown. The paper aims to investigate the underlying mechanisms by comparing the
      differences between i.m. and s.c. preadipocytes in glucose utilization, lipid
      metabolism, and the role of BMP signaling pathway. METHODS: Experiments were
      performed in porcine primary i.m. and s.c. preadipocytes in culture. The mRNA and
      protein expression patterns were determined respectively by Quantitative real
      time PCR and Western blot. Cytosolic triglycerides were examined by triglyceride
      assay. RESULTS: The i.m. preadipocytes consumed more glucose by expression of
      GLUT1 and s.c. preadipocytes mainly utilized exogenic fatty acids for lipid
      synthesis by expression of LPL and FAT. Meanwhile, the expression of genes
      related to lipogenesis and lipolysis in s.c. preadipocytes increased more quickly
      than those in i.m. preadipocytes. The expression patterns of the genes involved
      in BMP-Smad signaling pathway were consistent with those of the genes
      participated in adipocytes differentiation in both i.m. and s.c. preadipocytes.
      Exogenous BMP2 significantly increased, whereas Noggin and Compound C, remarkably
      decreased the triglycerides content in i.m. preadipocytes, without affecting s.c.
      preadipocytes. BMP2 shRNA significantly reduced the mRNA levels of the downstream
      genes of BMP-Smad signaling pathway and PPARgamma in both i.m. and s.c.
      preadipocytes. CONCLUSION: These findings suggested that the differentiation and
      lipid accumulation differences between i.m. and s.c. preadipocytes might be
      caused by the different manners of glucose utilization, lipid metabolism and the
      BMP-Smad signaling pathway. The special feature of i.m. adipocytes implied that
      these cells might be a potential target for treatment of diabetes.

PMID- 23860033
TI  - Dendritic spine density, morphology, and fibrillar actin content surrounding
      amyloid-beta plaques in a mouse model of amyloid-beta deposition.
AB  - Dendritic spines are the site of most excitatory synapses, the loss of which
      correlates with cognitive impairment in patients with Alzheimer disease.
      Substantial evidence indicates that amyloid-beta (Abeta) peptide, either
      insoluble fibrillar Abeta deposited into plaques or soluble nonfibrillar Abeta
      species, can cause spine loss but the concurrent contributions of fibrillar Abeta
      and nonfibrillar Abeta to spine loss has not been previously assessed. We used
      multiple-label immunohistochemistry to measure spine density, size, and F-actin
      content surrounding plaques in the cerebral cortex in the PSAPP mouse model of
      Abeta deposition. Our approach allowed us to measure fibrillar Abeta plaque
      content and an index of nonfibrillar Abeta species concurrently. We found that
      spine density was reduced within 6 MUm of the plaque perimeter, remaining spines
      were more compact, and F-actin content per spine was increased. Measures of
      fibrillar Abeta plaque content were associated with reduced spine density near
      plaques, whereas measures of nonfibrillar Abeta species were associated with
      reduced spine density and size but not altered F-actin content. These findings
      suggest that strategies to preserve dendritic spines in AD patients may need to
      address both nonfibrillar and fibrillar forms of Abeta and that nonfibrillar
      Abeta may exert spine toxicity through pathways not mediated by depolymerization
      of F-actin. 

PMID- 23860036
TI  - MicroRNA-22 downregulation by atorvastatin in a mouse model of cardiac
      hypertrophy: a new mechanism for antihypertrophic intervention.
AB  - BACKGROUND: Growing evidence shows that microRNAs (miRNAs) are involved in
      various cardiac processes including cardiac hypertrophy. However, the modulation
      of miRNA by pharmacological intervention in cardiomyocyte hypertrophy has not
      been disclosed yet. methods: We constructed neonatal rat cardiomyocyte
      hypertrophy induced by angiotensin II stimulation and subjected to cardiomyocyte
      immunochemistry, qRT-PCR and immunoblotting analysis. In addition, we constructed
      the mouse cardiac hypertrophy using angomir-22 stimulation and demonstrated the
      potential antihypertrophic mechnism of atorvastatin. RESULTS: The results showed
      that a collection of miRNAs were aberrantly expressed in hypertrophic
      cardiomyocytes induced by angiotensin II stimulation. In addition, overexpression
      of miR-22 was found in angiotensin II-induced hypertrophic cardiomyocytes,
      whereas administration of atorvastatin could reverse the upregulation of miRNA-22
      nearly back to the control level. Furthermore, up-regulation of miRNA-22 in
      cardiomyocytes in vitro and in vivo could induce cardiac hypertrophy, which could
      suppress the protein level of phosphatase and tensin homolog deleted on
      chromosome ten (PTEN). Concomitantly, the production of ANP, BNP and beta-MHC was
      enhanced and cardiomyocyte size was increased. However, atorvastatin could
      markedly knockdown miRNA-22 expression and reverse these changes in
      cardiomyocytes. These results suggest that the contribution of atrovastatin to
      cardiomyocyte hypertrophy may be involved in downregulation of miRNA-22
      expression, which modulates the activity of PTEN in cardiomyocyte hypertrophy.
      conclusion: This study demonstrates for the first time the modulation of miRNA-22
      can be achieved by pharmacological intervention. The data generated from this
      study provides a rationale for the development of miRNA-based strategies for
      antihypertrophic treatment.

PMID- 23860037
TI  - Autosomal recessive Adams-Oliver syndrome caused by homozygous mutation in EOGT,
      encoding an EGF domain-specific O-GlcNAc transferase.
AB  - Autosomal recessive Adams-Oliver syndrome was diagnosed in three remotely related
      Bedouin consanguineous families. Genome-wide linkage analysis ruled out
      association with known Adams-Oliver syndrome genes, identifying a single
      homozygosity ~1.8-Mb novel locus common to affected individuals (LOD score 3.37).
      Whole-exome sequencing followed by Sanger sequencing identified only a single
      mutation within this locus, shared by all affected individuals and found in
      patients from five additional apparently unrelated Bedouin families: a 1-bp
      deletion mutation in a predicted alternative splice variant of EOGT, leading to a
      putative truncated protein. RT-PCR demonstrated that the EOGT-predicted
      alternative splice variant is ubiquitously expressed. EOGT encodes EGF-domain
      specific O-linked N-acetylglucosamine transferase, responsible for extracellular
      O-GlcNAcylation of epidermal growth factor-like domain-containing proteins, and
      is essential for epithelial cell-matrix interactions. F-actin staining in
      diseased fibroblasts showed apparently intact cell cytoskeleton and morphology,
      suggesting the EOGT mutation acts not through perturbation of cytoskeleton but
      through other mechanisms yet to be elucidated. 

PMID- 23860038
TI  - Comment on Gialluisi et al.

PMID- 23860039
TI  - Testing personalized medicine: patient and physician expectations of next
      generation genomic sequencing in late-stage cancer care.
AB  - Developments in genomics, including next-generation sequencing technologies, are
      expected to enable a more personalized approach to clinical care, with improved
      risk stratification and treatment selection. In oncology, personalized medicine
      is particularly advanced and increasingly used to identify oncogenic variants in
      tumor tissue that predict responsiveness to specific drugs. Yet, the
      translational research needed to validate these technologies will be conducted in
      patients with late-stage cancer and is expected to produce results of variable
      clinical significance and incidentally identify genetic risks. To explore the
      experiential context in which much of personalized cancer care will be developed
      and evaluated, we conducted a qualitative interview study alongside a pilot
      feasibility study of targeted DNA sequencing of metastatic tumor biopsies in
      adult patients with advanced solid malignancies. We recruited 29/73 patients and
      14/17 physicians; transcripts from semi-structured interviews were analyzed for
      thematic patterns using an interpretive descriptive approach. Patient hopes of
      benefit from research participation were enhanced by the promise of novel and
      targeted treatment but challenged by non-findings or by limited access to
      relevant trials. Family obligations informed a willingness to receive genetic
      information, which was perceived as burdensome given disease stage or as
      inconsequential given faced challenges. Physicians were optimistic about long
      term potential but conservative about immediate benefits and mindful of elevated
      patient expectations; consent and counseling processes were expected to mitigate
      challenges from incidental findings. These findings suggest the need for
      information and decision tools to support physicians in communicating realistic
      prospects of benefit, and for cautious approaches to the generation of incidental
      genetic information. 

PMID- 23860040
TI  - Experiences of predictive testing in young people at risk of Huntington's
      disease, familial cardiomyopathy or hereditary breast and ovarian cancer.
AB  - While debate has focused on whether testing of minors for late onset genetic
      disorders should be carried out if there is no medical benefit, less is known
      about the impact on young people (<25 years) who have had predictive testing
      often many years before the likely onset of symptoms. We looked at the
      experiences of young people who had had predictive testing for a range of
      conditions with variable ages at onset and options for screening and treatment. A
      consecutive series of 61 young people who had a predictive test aged 15-25 years
      at the Clinical Genetic Service, Manchester, for HD, HBOC (BrCa 1 or 2) or FCM
      (Hypertrophic Cardiomyopathy or Dilated Cardiomyopathy), were invited to
      participate. Thirty-six (36/61; 59%) agreed to participate (10 HD, 16 HBOC and 10
      FCM) and telephone interviews were audiotaped, transcribed and analysed using
      Interpretative Phenomenological Analysis. None of the participants expressed
      regret at having the test at a young age. Participants saw the value of pretest
      counselling not in facilitating a decision, but rather as a source of information
      and support. Differences emerged among the three groups in parent/family
      involvement in the decision to be tested. Parents in FCM families were a strong
      influence in favour of testing, in HBOC the decision was autonomous but usually
      congruent with the views of parents, whereas in HD the decision was autonomous
      and sometimes went against the opinions of parents/grandparents. Participants
      from all three groups proposed more tailoring of predictive test counselling to
      the needs of young people. 

PMID- 23860041
TI  - The Moroccan Genetic Disease Database (MGDD): a database for DNA variations
      related to inherited disorders and disease susceptibility.
AB  - National and ethnic mutation databases provide comprehensive information about
      genetic variations reported in a population or an ethnic group. In this paper, we
      present the Moroccan Genetic Disease Database (MGDD), a catalogue of genetic data
      related to diseases identified in the Moroccan population. We used the PubMed,
      Web of Science and Google Scholar databases to identify available articles
      published until April 2013. The Database is designed and implemented on a three
      tier model using Mysql relational database and the PHP programming language. To
      date, the database contains 425 mutations and 208 polymorphisms found in 301
      genes and 259 diseases. Most Mendelian diseases in the Moroccan population follow
      autosomal recessive mode of inheritance (74.17%) and affect endocrine,
      nutritional and metabolic physiology. The MGDD database provides reference
      information for researchers, clinicians and health professionals through a user
      friendly Web interface. Its content should be useful to improve researches in
      human molecular genetics, disease diagnoses and design of association studies.
      MGDD can be publicly accessed at http://mgdd.pasteur.ma. 

PMID- 23860042
TI  - A homozygous 237-kb deletion at 1p31 identified as the locus for midline cleft of
      the upper and lower lip in a consanguineous family.
AB  - Orofacial clefts are congenital defects that vary widely in type and severity,
      and can occur in isolation or in association with a variety of other defects.
      Herein, we describe a consanguineous family afflicted with a unique form of
      orofacial clefting manifesting as a facial midline defect that also involves
      mandibular and maxillary structures. All four affected sibs had median clefts of
      the upper and lower lips, tooth misalignment, and poor oral hygiene. Linkage
      analysis of 17 family members identified a 15.3-Mb pair recessive locus at 1p31
      with a LOD score of 3.63. To the best of our knowledge, this is, to date, the
      first locus reported for facial midline clefting and the first recessive locus
      for an isolated orofacial defect. The locus harboured a novel intergenic deletion
      of 273 164 bp, for which all fully affected sibs were homozygous. We did not note
      any potentially pathogenic gene variant at the 1p31 locus via exome-sequencing
      analysis. The identified deletion could be harbouring a regulatory element for
      the gene associated with the orofacial defect. The best candidate for the
      putative target gene is LHX8, located 49 149 bp upstream of the deletion. The
      gene is known to be associated with facial development in several animals. Four
      other family members had a subclinical phenotype--a simple notch in the lower lip
      or an increase in the interdental distance between the lower incisors--indicative
      of very low-level expression of the trait.

PMID- 23860043
TI  - Reply to ten Kate et al.

PMID- 23860044
TI  - The strength of combined cytogenetic and mate-pair sequencing techniques
      illustrated by a germline chromothripsis rearrangement involving FOXP2.
AB  - Next-generation mate-pair sequencing (MPS) has revealed that many constitutional
      complex chromosomal rearrangements (CCRs) are associated with local shattering of
      chromosomal regions (chromothripsis). Although MPS promises to identify the
      molecular basis of the abnormal phenotypes associated with many CCRs, none of the
      reported mate-pair sequenced complex rearrangements have been simultaneously
      studied with state-of-the art molecular cytogenetic techniques. Here, we studied
      chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with
      global developmental and psychomotor delay and severe speech disorder. We
      identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of
      FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for
      the global developmental and psychomotor delay. Our study confirmes the power of
      MPS for detecting breakpoints and truncated genes at near nucleotide resolution
      in chromothripsis. However, only by combining MPS data with conventional G
      banding and extensive fluorescence in situ hybridizations could we delineate the
      precise structure of the derivative chromosomes. 

PMID- 23860045
TI  - An efficient method for long-term room temperature storage of RNA.
AB  - RNA is a tool used in many fields, from molecular and cellular biology to
      medicine and nanotechnology. For most of these uses, the integrity of RNA is
      required and must be maintained during storage. Even though freezing is currently
      the storage method of choice, the increasing number of samples to be stored and
      the costly use of a cold chain have highlighted the need for room temperature
      preservation methods. Here, we report a new room temperature technology that
      consists in drying RNA samples in the presence of a stabilizer in stainless steel
      minicapsules. These air- and water-tight capsules isolate RNA from the atmosphere
      and maintain an anhydrous and anoxic environment. Through the evaluation of RNA
      integrity over time at room temperature or 90  degrees C, we identified
      atmospheric humidity as a major deleterious factor. The degradation rate
      dependence in temperature fitted an Arrhenius model, with an activation energy of
      28.5 kcal/mol and an extrapolated room temperature degradation rate of 3.2 10(
      13)/nt/s (95% confidence interval: 2.3-4.2/nt/s). In these conditions, it is
      expected that an RNA molecule will be subjected to 0.7-1.3 cut every 1000
      nucleotides per century. In addition, we showed that stored RNA is compatible for
      further analyses, such as reverse transcription-quantitative PCR. No significant
      change in the Cq values was observed over a simulated period of several decades.
      At last, our data are consistent with a sequence-independent degradation rate of
      RNA in the solid state. 

PMID- 23860047
TI  - An unusual clinical severity of 16p11.2 deletion syndrome caused by unmasked
      recessive mutation of CLN3.
AB  - With the introduction of array comparative genomic hybridization (aCGH)
      techniques in the diagnostic setting of patients with developmental delay and
      congenital malformations, many new microdeletion syndromes have been recognized.
      One of these recently recognized microdeletion syndromes is the 16p11.2 deletion
      syndrome, associated with variable clinical outcomes including developmental
      delay, autism spectrum disorder, epilepsy, and obesity, but also apparently
      normal phenotype. We report on a 16-year-old patient with developmental delay,
      exhibiting retinis pigmentosa with progressive visual failure from the age of 9
      years, ataxia, and peripheral neuropathy. Chromosomal microarray analysis
      identified a 1.7-Mb 16p11.2 deletion encompassing the 593-kb common deletion
      (~29.5 to ~30.1 Mb; Hg18) and the 220-kb distal deletion (~28.74 to ~28.95 Mb;
      Hg18) that partially included the CLN3 gene. As the patient's clinical findings
      were different from usual 16p11.2 microdeletion phenotypes and showed some
      features reminiscent of juvenile neuronal ceroid-lipofuscinosis (JNCL, Batten
      disease, OMIM 204200), we suspected and confirmed a mutation of the remaining
      CLN3 allele. This case further illustrates that unmasking of hemizygous recessive
      mutations by chromosomal deletion represents one explanation for the phenotypic
      variability observed in chromosomal deletion disorders. 

PMID- 23860046
TI  - Genome-wide estimates of inbreeding in unrelated individuals and their
      association with cognitive ability.
AB  - The consequence of reduced cognitive ability from inbreeding has long been
      investigated, mainly restricted to cousin-cousin marriages. Molecular genetic
      techniques now allow us to test the relationship between increased ancestral
      inbreeding and cognitive ability in a population of traditionally unrelated
      individuals. In a representative UK sample of 2329 individuals, we used genome
      wide SNP data to estimate the percentage of the genome covered by runs of
      homozygous SNPs (ROH). This was tested for association with general cognitive
      ability, as well as measures of verbal and non-verbal ability. Further,
      association was tested between these traits and specific ROH. Burden of ROH was
      not associated with cognitive ability after correction for multiple testing,
      although burden of ROH was nominally associated with increased non-verbal
      cognitive ability (P=0.03). Moreover, although no individual ROH was
      significantly associated with cognitive ability, there was a significant bias
      towards increased cognitive ability in carriers of ROH (P=0.002). A potential
      explanation for these results is increased positive assortative mating in spouses
      with higher cognitive ability, although we found no evidence in support of this
      hypothesis in a separate sample. Reduced minor allele frequency across the genome
      was associated with higher cognitive ability, which could contribute to an
      apparent increase in ROH. This may reflect minor alleles being more likely to be
      deleterious. 

PMID- 23860048
TI  - Histopathological review of breast tumours in children and adolescents in Delta
      State Nigeria.
AB  - BACKGROUND: Breast swellings in children and adolescents may be overlooked on
      assumption that they are physiological enlargement. Pathologic swellings
      including cancers have however been encountered in this age group. This study
      highlighted the spectrum of tumours in childhood and adolescents. MATERIALS AND
      METHODS: This was a 7 year retrospective analysis of all histologically diagnosed
      breast tumours in people aged 0 - 19 years. RESULTS: There were 134 breast tumour
      diagnoses occurring in 133 females and 1 male (gynaecomastia). One hundred and
      nineteen cases (88.8%) were recorded in the 10 - 14 year age group and 15 cases
      (11.2%) in the 15 - 19 year age group. No case was found in children aged less
      than 10 years. The most common tumour was fibroadenoma accounting for 75.4% (n =
      101) of all tumours followed by tubular adenoma (n = 11; 8.2%) and adenosis (n =
      10; 7.4%). No case of malignancy was recorded in this study. CONCLUSION:
      Fibroadenoma is the most common breast tumour in children and adolescents in our
      environment.

PMID- 23860049
TI  - Do we need imaging to diagnose appendicitis in children?
AB  - BACKGROUND: To evaluate the role of clinical assessment with selective use of
      imaging studies in the management of suspected acute appendicitis in children.
      PATIENTS AND METHODS: Medical records of children referred to Emergency Room in
      2010 for suspected appendicitis were retrospectively reviewed. Diagnostic
      investigations divided by age and sex were related to pathological findings.
      Negative appendectomy and complication rates were calculated. RESULTS: 923
      children needed surgical assessment : In 75.7% of them surgical indication was
      excluded and 24.3% were admitted to surgical ward for observation. Appendectomy
      was eventually performed in 137 patients (61.9%), 82.4% of them without any
      preoperative imaging while 17.6% underwent selective studies, mainly abdominal
      ultrasonography (14.6%). Imaging was requested twice as frequently in not
      operated admitted children (39.3%) than in the operated ones (17.5%, P < 0.001).
      Overall complicated appendicitis rate (peritonitis and abscess) resulted 26.4%
      and negative appendectomy rate 8.8%. Females older than 10 years presented
      histologically not-confirmed appendicitis in 22.2% of cases, while the younger
      ones presented more frequently complicated appendicitis (29.3%). CONCLUSIONS:
      Clinical assessment is the key to diagnose appendicitis. Nevertheless, in girls
      older than 10 years, selected use of imaging should be implemented to avoid
      unnecessary appendectomies. Imaging of choice in equivocal cases should be
      ultrasonography.

PMID- 23860050
TI  - The comparative study of the outcomes of early and late oral feeding in
      intestinal anastomosis surgeries in children.
AB  - BACKGROUND: A leakage of intestinal anastomosis is typically regarded as a
      devastating post-operative complication. Traditionally its believed that long
      fasting after intestinal surgery protect anastomosis site and most surgeons
      applied this method. Post-operative long fasting has many physical and mental
      adverse effects, especially in children, but its benefit has not proven yet. This
      study aimed to compare the outcomes of early and late oral feeding in intestinal
      resection and anastomosis surgery in children. PATIENTS AND METHODS: This
      randomized, double-blind controlled trial evaluated the outcome of early-feeding
      following in children aged 1 month to 12 years who underwent intestinal resection
      and anastomosis and compared the results with those who had late-feeding. The
      results were anlysed for fever, nausea and vomiting, abdominal distension, first
      passage of gas and stool were also evaluated hospital stay time, major post
      operative complications such as anastomosis leakage, wound infection or
      dehiscence, intra-abdominal abscess between the two groups. RESULTS: The mean
      time of first oral feeding in the early feeding group (study group) was 2.5 +/-
      0.7 days but it was 5.3 +/- 0.6 days in the late feeding group (control group).
      There was no mortality in both groups. There was no difference in major
      complications in both groups (anastomosis leakage). In the study group, first
      defecation time was shorter than the control group (3.7 days v. 4.4 days) and
      they had less hospital stay also (5.2 days vs. 8.3 days) and lower cost of
      hospitalization. CONCLUSION: Early oral feeding after intestinal resection and
      anastomosis in children is a safe method, it has many benefits and does not
      increase the major or minor post-operative complications (anastomosis leakage)
      long time fasting is not necessary and has not any beneficial effect and early
      feeding increases satisfaction of the parents and children, and reduce hospital
      stay and costs.

PMID- 23860051
TI  - Anterior sagittal anorectoplasty: An alternative to posterior approach in
      management of congenital vestibular fistula.
AB  - BACKGROUND: Better exposure, possibility of extension if needed and precise
      placement of the anal canal within the external sphincter complex have made the
      posterior and anterior sagittal approaches more popular and established for the
      correction of anovestibular fistula. The mini posterior sagittal anorectoplasty
      (PSARP) was the procedure of choice for female ARM at our center till date. As an
      alternative surgical option, we performed anterior sagittal anorectoplasty
      (ASARP) in 15 cases of anovestibular fistula and compared them with 12 cases of
      vestibular fistula operated by PSARP technique. PATIENTS AND METHODS: Fifteen
      female infants with vestibular fistula who had anterior sagittal anorectoplasty
      (ASARP) procedure were reviewed. The procedure and its outcome were evaluated.
      RESULTS: The manoeuvering during anesthesia and operative access were quite
      easier in ASARP compared to PSARP. Delineation of plane in ASARP between rectum
      and vagina was easier and clearer in comparison to PSARP. Rent occurred in the
      posterior vaginal wall in three cases of ASARP and two cases of PSARP. There were
      two cases of wound infection in each group. Three cases of PSARP group developed
      anal stenosis and constipation while one in the ASARP group developed
      constipation. CONCLUSION: Anesthesia and access in ASARP makes it an easier
      alternative option to PSARP in the management of anovestibular fistula in girls.

PMID- 23860052
TI  - Primary duodenal tuberculosis presenting as gastric-outlet obstruction: Its
      diagnosis.
AB  - INTRODUCTION: Gastrointestinal tuberculosis often involves the ileocecal region.
      Duodenal and gastric tuberculosis found in only 1% of patients suffering from
      pulmonary tuberculosis with associated HIV infection in non-endemic areas.
      Duodenal obstruction due to tuberculosis is very rare and needs high index of
      suspicions for diagnosis. Mostly this entity is suspected on intraoperative
      findings. In this manuscript we emphasized on ways and means for establishing
      histopathological diagnosis before starting anti-tubercular treatment in such
      cases. METHOD AND MATERIAL: All patients of suspected gastroduodenal tuberculosis
      presented with feature of gastric-outlet obstruction managed during Jan 2009 to
      June 2011 were included in the study. After proper evaluation (routine
      hematological and biochemical examination, microbiological examination,
      serological and endoscopic evaluation) exploratory laparotomy was done and if
      there is no mesenteric lymphadenopathy or it is not safe to take biopsy form the
      diseased duodenum, multiple FNAC were taken from the diseased portion for
      histopathological and microbiological diagnosis. RESULT: A total of five patients
      were treated during this period. The most common presentation was vomiting
      followed by failure to thrive and weight loss; two patients had abdominal pain.
      Biopsy of mesenteric lymph node was possible in two cases. FNAC from diseases
      portion was taken in all cases. FNAC showed granulomas in four cases. Cases where
      even FNAC finding was non-conclusive on HPE/Microbiology was not subjected to
      antitubercular drug. CONCLUSION: Multiple intra-operative FNAC may be taken from
      the diseased portion of the duodenum to establish the histopathological diagnosis
      if diagnosis is not established by any other mean.

PMID- 23860053
TI  - Intussusception in children: Comparison between ultrasound diagnosis and
      operation findings in a tropical developing country.
AB  - BACKGROUND: Intussusception is one of the more common causes of intestinal
      obstruction in children. The diagnosis may be based mainly on clinical features;
      however, there are no classic signs and symptoms that are common to all cases.
      This study reports our experience at US diagnosis and operation findings of
      children with intussusceptions in a tropical developing economy. MATERIALS AND
      METHODS: This was an 8 years retrospective review of intussusceptions in children
      in a tertiary health facility in a tropical developing country from January 2004
      to December 2011. RESULTS: Twenty-five out of 41 children (M:F = 2.2:1) admitted
      with intussusceptions within the period were studied. The median age was 6.0 +/-
      5.57 months (range 3 months- 7 years). US positively diagnosed intussusceptions
      in 20 (80%) cases. CONCLUSION: US can increase diagnostic confidence in
      intussusceptions.

PMID- 23860054
TI  - The comparison of the intestinal adaptation effects of subcutaneous and oral
      insulin in a rats with short bowel syndrome.
AB  - AIM: Insulin has been reported to have positive effects on intestinal adaptation
      after short bowel syndrome when applicated oral or subcutaneously. The purpose of
      this study is to compare the intestinal adaptation effects of subcutaneous and
      oral routes of insulin in rats with short bowel syndrome. MATERIALS AND METHODS:
      The short bowel syndrome (SBS) was performed through 70-75% of small intestinal
      resection and an end-to-end anastomosis. The control group rats underwent SBS
      only. In the second group, oral insulin (1 U/ml) was administrated twice-daily.
      In the last group, the insulin was administrated subcutaneously (1 U/kg) as in
      the control group. All rats were killed on day 15. Outcome parameters were weight
      of small intestine, the crypt length, villous depth, the blood levels of vascular
      endothelial growth factor (VEGF), and granolocyt-monocyst colony-stimulating
      factor (GMCSF). RESULTS: Intestinal weight was significantly more in oral insulin
      group and subcutaneous insulin group than in the control group (72.6 +/- 4.3,
      78.6 +/- 4.8 and 59.7 +/- 4.8) (P < 0.05). There was no difference between the
      groups according to villus length, crypt depth, and villous/crypt ratio both in
      proximal and distal parts of the resected bowel (P > 0.05). VEGF values were not
      statistically significant between the groups (200.3 +/- 41.6, 178.9 +/- 30.7 and
      184.3 +/- 52.2) (P > 0.05). GMCSF was statistically higher in the control group
      than in other groups (3.34 +/- 1.34, 1.56 +/- 0.44 and 1.56 +/- 0.44) (P < 0.05).
      CONCLUSION: Insulin has positive effects on intestinal adaptation in short bowel
      syndrome. Subcutaneous administration is slightly more effective than the oral
      route.

PMID- 23860055
TI  - Paediatric laparoscopic hernia repair: Ex vivo skills in the reduced training
      era.
AB  - INTRODUCTION: Changes to surgical working hours have resulted in shorter training
      times and fewer learning opportunities. Tools that develop surgical skills ex
      vivo are of particular interest in this era. Laparoscopic skills are regarded as
      essential by many for modern paediatric surgery practice. Several generic skills
      models have been reported and validated. However, there is limited evidence
      regarding the role of procedure specific models. Here, a laparoscopic paediatric
      hernia repair model is trialled with surgical trainees and their competence
      compared with consultant colleagues. PATIENTS AND METHODS: An ex-vivo paediatric
      inguinal hernia repair model was devised. Surgical trainees from 5 specialist
      centres were recruited and performed multiple standardised repairs. RESULTS: 23
      trainees performed 192 repairs. Experts performed 10 repairs for comparison.
      Trainees were timed performing the repair and their accuracy measured. With
      repeated attempts trainee's timings and accuracy improved until by the 10 th
      repair they were no different from benchmark consultant scores. CONCLUSION: A
      simple, procedure specific ex-vivo training model has been evaluated for
      laparoscopic hernia training in paediatric surgery. The results suggest
      improvements in competence with repetition. Trainee and benchmark consultant
      scores are no different by the 10 th trainee attempt. We conclude that this model
      may have a valuable role in the training and assessment of future paediatric
      surgeons.

PMID- 23860056
TI  - Clinico-pathological patterns of a rare presentation of abdominal neuroblastoma
      in children.
AB  - BACKGROUND: To study the diagnosis, management, and outcome of abdominal
      neuroblastoma (NBL) in infants and children and also the behavior of some rare
      types. PATIENTS AND METHODS: This is a retrospective review of 46 infants and
      children having abdominal NBL at King Abdulaziz University Hospital, Jeddah,
      Kingdom of Saudi Arabia and Tanta University Hospital, Tanta, Egypt (a joint
      study) between February 2008 and January 2012. The patients' medical records were
      reviewed for demographic details, clinical presentations, histopathology,
      radiological diagnosis, management, and outcome. RESULTS: Of the 46 patients, 5
      (10.7%), three males and two females, aged 1.5-6.5 years (mean: 4.5 years) had
      rare types of NBL (one bilateral NBL, one pelvic NBL, one pelvic-abdominal, and
      there were two cases of ganglioneuroblastoma). Three patients (two
      ganglioneuroblastoma and one pelvic) underwent complete surgical removal of the
      tumor with a good disease survival, whereas the other two patients (two bilateral
      and one pelviabdominal) had advanced disease and received palliative
      chemoradiotherapy. The remaining 41 patients, 23 males (56.1%) and 18 females
      (43.9%), with mean age 3.9 years (range: 1-7 years), had unilateral abdominal
      NBL. Twelve of them had resectable tumor and underwent primary surgical removal
      of the tumor, whereas the remaining 29 patients had unresectable tumor and
      received pre-operative chemotherapy with good response of the tumor in seven
      patients and no response in the remaining 22 patients. CONCLUSION: Primary
      complete surgical removal of tumor is advisable in localized NBL with a good
      outcome, whereas in advanced cases, it is better to start with pre-operative
      chemotherapy to downsize the tumour mass and safe delayed surgical excision. An
      increase in patient's age is associated with advanced stage of NBL and poor
      prognosis except in ganglioneuroblastoma cases due to maturation of tumor cells.

PMID- 23860057
TI  - Acute cholecystitis from typhic origin in children.
AB  - BACKGROUND: To evaluate the particularities of typhoid cholecystitis in children.
      MATERIALS AND METHODS: This was a 5-year prospective study of typhoid
      cholecystitis in children under 15 years old at Djougou and Sylvanus Olympio
      teaching hospital. The diagnosis of typhoid cholecystitis was based on clinical
      and investigation findings, confirmed by operative findings at cholecystectomy.
      RESULTS: Six children with typhoid acalculous cholecystitis were treated over a
      five-year period (4 males and 2 females). Their ages ranged from five to 13 years
      (median 8.8 years). The mean duration of symptoms was six to 21 days. The
      clinical signs were fever, abdominal pain, which predominated at the right upper
      abdominal quadrant, and type II Hackett splenomegaly. The diagnosis was confirmed
      by a positive Widal's test and Salmonella typhi isolation from the culture in all
      patients; four patients had ultrasound evidence of acalculous cholecystitis. Open
      cholecystectomy was successful in the six cases. The operative findings were
      gangrene (3), perforation (2) and empyema (1). All the patients made an
      uneventful recovery, and have remained symptom free one and three months on
      follow-up. CONCLUSION: Typhoid acalculous cholecystitis is a frequent
      complication in children. Late presentation and diagnosis is associated with
      complications. Cholecystectomy in association with antibiotic is the treatment of
      choice.

PMID- 23860058
TI  - Spontaneous biliary peritonitis: Is bed side diagnosis possible?
AB  - BACKGROUND: Spontaneous biliary peritonitis is a rare cause of acute abdomen. In
      spontaneous biliary peritonitis there is perforation in the wall of the extra
      hepatic or intra-hepatic duct occurs without any traumatic or iatrogenic injury
      and have been described more often in neonates. The symptoms may be acute or
      insidious delaying the diagnosis. Present manuscript deals with diagnosis and
      management of these cases. MATERIALS AND METHODS: This is a prospective study and
      all patients of suspected biliary peritonitis presented during Dec 2010 to Feb
      2012 were included in the study. After preliminary investigations in all patients
      abdominal paracentesis was done and in cases where intra-abdominal fluid
      bilirubin level was several fold higher than serum bilirubin level were subjected
      to exploratory laparotomy. Further investigation like T-tube cholangiogram and
      magnetic resonance cholangiopancreatography (MRCP) was done to rule out
      choledochal cyst before leveling these cases as SPBD. RESULTS: A total of 6
      patients were included in present series commonest presenting symptom was
      progressive abdominal distension without signs of overt peritonitis followed by
      progressive jaundice, fever and abdominal pain. On exploration site of
      perforation was observed in 50% of cases and in 50% of cases bile duct was not
      dilated. Second surgery was not required in 34% of cases. There was no mortality
      or significant morbidity in our series. CONCLUSION: Spontaneous perforation of
      bile duct is rare disease and high index of suspicion is required for diagnosis.
      Simple bed side test can help in diagnosis but T tube cholangiogram or MRCP are
      must to rule out choledochal cyst.

PMID- 23860059
TI  - Paediatric laparoscopic orchidopexy as a novel mentorship: Training model.
AB  - BACKGROUND: Although Laparoscopy is becoming a standard procedure in management
      of pediatric urology disorders, but its widespread use still limited. This can be
      attributed mainly to difficulty in acquiring such specialized technique,
      especially by post graduate practicing urologist. Thus, we herein evaluate the
      impact of condensed laparoscopic training programme in children hospital with the
      aim to analyze the feasibility and safety of laparoscopic orchidopexy in training
      basic laparoscopic skills. The aim of this study was to review experience as a
      mentor in training laparoscopic skills through condensed training programme based
      on high volume low risk procedure of pediatric laparoscopic orchidopexy.
      MATERIALS AND METHODS: In order to implement a condensed laparoscopic curriculum
      in a short period of time while maintaining utmost patient safety, laparoscopic
      orchidopexy was used as the technique of choice. The course was conducted over a
      period of 5 days starting from 1 st November 2010 in a tertiary pediatric
      surgical center under guidance of an expert mentor. A total of 30 testicular
      units in 27 pediatric patients of different age group diagnosed with impalpable
      undescended testis underwent laparoscopic intervention. The course was conducted
      in three stages with the aim to deliver laparoscopic skills to trainee. In stage
      one out of eight cases operated by mentor with assistance of trainee six were
      operated on day 1 and two cases were operated on second day. The trainee
      performed 12 cases of laparoscopy independently with assistance of mentor in
      stage two which was carried out on day 2, 3 and 4. Finally all 7 cases including
      two second stage laparoscopic orchidopexy procedures were carried out
      independently by trainee under observer ship of mentor in stage three during day
      4 and 5 of training programme. The feasibility and efficacy of laparoscopic
      orchidopexy in training laparoscopic skills through condensed training programme
      was assessed through analysis of mentorship experience.

PMID- 23860060
TI  - Outcome of tube thoracostomy in paediatric non-traumatic pleural fluid
      collections.
AB  - OBJECTIVE: Management of pleural fluid collection not due to trauma increases
      workload of the paediatric thoracic surgeons, while delay or inappropriate
      treatment worsens the prognosis of the disease. This study aimed at assessing the
      outcome of therapeutic tube thoracostomy in non-traumatic paediatric pleural
      fluid collections and identifying factors responsible for treatment failure with
      tube thoracostomy. DESIGN: Prospective analysis of socio-demographic
      characteristics, clinical features, clinical diagnosis, radiological diagnosis,
      and bacteriological diagnosis including bacteria cultured with sensitivity
      pattern, also treatment offered including tube thoracostomy with duration of tube
      thoracostomy and length of hospitalisation, indication for additional surgical
      procedure with type, and outcome of treatment of 30 paediatric patients with non
      traumatic pleural fluid collection. RESULTS: Thirty paediatric patients with
      various causes of non-traumatic pleural fluid collection in 34 pleural spaces
      were analysed. Their ages ranged between six months and 16 years (mean = 6.5
      years) and M:F ratio of 2:1. Pleural effusion and empyema thoracis accounted for
      46% and 40% with staphylococcus aureus and streptococcus pneumoniae cultured in
      10% each and a high negative culture rate of 46%, which was higher with age. The
      parents of 40% of the patients belonged to social class 3. Success rate of tube
      thoracostomy was 86% in unilateral cases, 50% in bilateral cases and 81% in all
      cases. Alternative treatment with thoracotomy and decortications gave a success
      rate of 100%. CONCLUSION: Thoracotomy with decortication is superior to tube
      thoracostomy in paediatric non-traumatic pleural fluid collection and should be
      chosen as the primary treatment option when there is bilateral disease,
      chronicity, loculated effusion, thickened pleural membranes or trapped lung.

PMID- 23860061
TI  - Diagnostic value of high resolution ultrasound in localisation of the undescended
      testis in children.
AB  - BACKGROUND: The use of ultrasonography in the pre-operative localisation of
      undescended testes has become controversial due to fears about its accuracy. This
      study was designed to ascertain the accuracy, sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of ultrasonography in
      the localisation of the undescended testes in children. PATIENTS AND METHODS: A
      prospective evaluation of all boys undergoing operation for undescended testes at
      the Lagos University Teaching Hospital, Idi-Araba, Lagos, over a 12 month period
      was performed. The pre-operative clinical and ultrasound findings were compared
      with the findings on surgical exploration. RESULTS: Forty boys with 52
      undescended testes were studied. The mean age of the boys at the time of surgery
      was 4.0 +/- 0 years (range 1-11 years). Forty-six (88.5%) testes were localised
      pre-operatively by ultrasound- 20 of 22 (90.9%) palpable testes and 26 of 30
      (86.7%) non-palpable testes. Intra-operatively, 49 (94.2%) of the undescended
      testes were found while 3 (5.8%) were absent/vanishing testes. Ultrasound
      evaluation had an accuracy of 86.5%, sensitivity of 89.8%, and specificity of
      33.3%, PPV of 95.7% and a NPV of 16.7%. CONCLUSION: Ultrasound assessment is
      beneficial in pre-operative evaluation of children with undescended testes.

PMID- 23860062
TI  - Superior repair: A useful approach for some anatomic variants of total anomalous
      pulmonary venous connection.
AB  - BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) occurs when all
      the four pulmonary veins drain to the right atrium or to tributaries of the
      systemic veins. There have been various published techniques for the repair but
      none has been agreed on for the different anatomical variants that may be
      encountered during surgery. PATIENTS AND METHODS: Between January 2005 and June
      2010 the data of 6 of 18 patients who had surgical repair using the superior
      approach were retrospectively reviewed.Three patients had long narrow venous
      stalk connecting the coronary sinus to venous confluence; two had the right
      pulmonary veins draining to superior vena cava (SVC) and left pulmonary veins to
      left lateral wall of SVC and one had an obstruction at entrance of Pulmonary Vein
      into venous confluence. RESULTS: Five patients initially had the superior
      approach while one had transatrial with unroofing of the coronary sinus. Two had
      a concomitant Wardens procedure. The mean aortic cross clamping was 87.5 (60-125)
      min, the mean cardiopulmonary bypass time should have min as unit of 127.8 (100
      180), the mean Intensive Care Unit (ICU) stay of 2.5 (2-4) days and the mean
      hospital stay 8.2 (7-9) days. One patient died at early post-operation from low
      cardiac outputand five had an uneventful post-operative course and had remained
      stable until date. CONCLUSION: In our experience, the superior approach was an
      effective alternative approach for some anatomic variants of TAPVC that may be
      unexpectedly encountered during operation and also useful surgical approach for
      older children.

PMID- 23860063
TI  - Paediatric urologic pathologies at the national teaching hospital in Cotonou: A
      etiological and therapeutic aspects.
AB  - BACKGROUND: Urological pathologies of children are dominated by congenital
      malformations of the kidneys and urinary tract. Their management is often
      surgical. The objective of this survey was to study etiological and therapeutic
      aspects of urological presentations in children. PATIENTS AND METHODS: Data for
      aetiology, treatment, and results in children hospitalized at the Paediatric
      Surgery service of National Teaching Hospital (CNHU) in Cotonou were
      retrospectively analyzed from January 1999 to December 2008. RESULTS: A total of
      214 patients with complete data were evaluated. Urological pathologies
      represented 4.8% of the hospitalizations in paediatric surgery, with an incidence
      of 21 cases per year. The mean age was 4.9 +/- 3.2 years (age 1 week to 14
      years). The male to female ratio was 14:14. Cryptorchidism, hydrocele,
      nephroblastoma, the posterior urethral valves, ureteropelvic junction
      obstructions, post-circumcision haemorrhage and hypospadias were the most
      frequent pathologies. Congenital urological malformations represented 81.3%,
      followed neoplastic pathologies (7.9%), traumatic pathologies (6.1%) and others
      (4.7%). The disorders of male genitalia were more frequent and constituted 68.2%
      of the cases. The anomalies of the urinary tract were 30.8% and intersex
      disorders were 0.9%. The average age of the children urological pathologies at
      the time of consultation was 8.85 +/- 4.6 years. The treatment was often surgical
      with a mortality of 2.8%.

PMID- 23860064
TI  - Hydatid cyst in children: A 10-year experience from Iran.
AB  - BACKGROUND: Hydatid disease is one of the major world-wide health problems
      especially in endemic countries. Due to lack of statistics about this disease,
      various aspects of hydatidosis in children in North-West of Iran have been
      studied in this study. MATERIALS AND METHODS: We studied 59 children with
      hydatidosis referring Tabriz Children Hospital, Tabriz, Iran from 2001 up to
      2011. We surveyed chief complaint of patients, number, size and location of cysts
      in children and also we studied cysts as if they are infected or ruptured or not.
      RESULTS: Average age of 59 patients (32 [54.2%] males and 27 [45.8%] females) was
      7.93 +/- 3.0. The most common chief complaints were cough and pain. Number of
      cysts was higher in females (2.00 +/- 2.8 vs. 1.52 +/- 1.0). The most common
      locations of cysts are lung and liver (52 patients); however, other organs had
      been also affected. CONCLUSIONS: Lung hydatidosis is more common than hepatic
      hydatidosis in children than adults and it is more frequent in males. Hydatid
      disease should be considered in differential diagnoses of liver and lung cystic
      lesions in children.

PMID- 23860065
TI  - Utilization of banked blood in pediatric surgical procedures in Calabar, Nigeria.
AB  - BACKGROUND: Performing major surgery in a child demands that blood is cross
      matched and saved to be transfused as indicated. Because the cost of cross
      matching and donation of blood can be enormous and may equal or surpass the cost
      of surgery in our setting, it is pertinent to evaluate its utilization. The aim
      of this study was to determine how banked blood meant for pediatric surgical
      procedures was utilized with the hope of streamlining our blood requisition
      policy. This may be useful to pediatric and other surgeons involved in the
      operative care of children in similar settings. MATERIALS AND METHODS: This was a
      prospective study of all children who had ELECTIVE or EMERGENCY surgical
      procedures between January 2009 and June 2010. The age, sex, nature of surgery,
      blood loss, banked units of blood and amount transfused were collected and
      analyzed. RESULTS: Eighty two patients had 81 units of blood banked for them.
      Forty - eight and half units (59.9%) of the banked blood were for the emergency
      group but only 18 units (22.2%) were actually transfused at the end (P = 0.044)
      leading to inadequate use of the product. CONCLUSION: Banking large quantities of
      blood but utilizing only little is tantamount to inadequate use and delays
      surgical intervention. Indirectly, it increases cost of surgery. There is need to
      rationalize our blood ordering habits without causing harm to patients.

PMID- 23860066
TI  - Tonsillectomy: Vasoconstrictive hydrolytic cold dissection method.
AB  - BACKGROUND: Tonsillectomy, a common paediatric otolaryngology procedure, has
      undergone several evolutionary trends in the surgical techniques aimed at
      minimizing complications and improving patients' satisfaction. Despite the
      technological advancements in this respect, search for an ideal method is still
      ongoing, and some authorities are reverting back to the conventional methods. We
      wish to introduce the "Vasoconstrictive hydrolytic cold dissection" (VHCD)
      method. PATIENTS AND METHODS: The VHCD method was described, and the outcome
      measures in one hundred and thirty-five patients who had the procedures were
      presented in . Data entrance was done with SPSS 14. RESULTS: A total 135 patients
      comprising of 107 children aged 1-12 years and 28 adolescents/adults aged 14-52
      years were operated upon using the VHCD between March 2009 and July 2012 by the
      same teams of Surgeons and Anaesthetists. The average surgical time and blood
      volume losses were 15 minutes and 5 mls for children and 12 mins and 10 mls for
      adults/adolescents, respectively. There was a single case (0.7%) of post
      tonsillar bleed (reactionary haemorrhage). The rest (99.3%) recorded nil
      haemorrhage within and beyond first 2 weeks post-surgery. CONCLUSIONS: Surgeons
      used to other techniques of tonsillectomies may not revert to the cold steel;
      however, those practicing CSM will benefit from VHCD. We hereby recommend this
      simple, cost-effective modification of the cold steel tonsillectomy, which
      appears to have made dissection easier and also minimizes haemorrhage, a common
      complication of tonsillectomy surgery. It is timely in the advent of increased
      advocacy towards reversal to the conventional method of tonsillectomy. A
      randomized control trial is required for further evaluation of this method.

PMID- 23860067
TI  - Traumatic brain injuries in children: A hospital-based study in Nigeria.
AB  - BACKGROUND: Traumatic Brain Injury (TBI) is a significant cause of morbidity and
      mortality worldwide. Our previous studies showed a high frequency of motor
      vehicle accidents among neurosurgical patients. However, there is a dearth of
      data on head injuries in children in Nigeria. AIMS: To determine the epidemiology
      of paediatric traumatic brain injuries. SETTING AND DESIGN: This is a prospective
      analysis of paediatric head trauma at the University of Benin Teaching Hospital,
      a major referral centre for all traumatic brain injuries in Nigeria between
      October 2006 and September 2011. MATERIALS AND METHODS: We studied the
      demographic, clinical and radiological data and treatment outcomes. Data was
      analysed using statistical package for the social sciences (SPSS) 16.0. RESULTS:
      We managed 127 cases of paediatric head injuries, 65 boys and 62 girls
      representing 13% of all head injuries managed over the 5-year period. They were
      aged 3 months to 17 years. The mean age was 7.4 years (median 7 years) with peak
      incidence occurring at 6-8 years i.e. 31 (24.4%) cases. Motor vehicle accidents
      resulted in 67.7%, falls 14% and violence 7%. The most frequent computed
      tomography finding was intracerebral haemorrhage. Mean duration of
      hospitalization was 18 days (median 11 days). Eleven patients died, mortality
      correlating well with severity and the presence of intracerebral haematoma.
      CONCLUSION: Head injuries in children are due to motor vehicle and motor vehicle
      related accidents. Hence, rational priorities for prevention of head injuries in
      children should include prevention of vehicular, especially pedestrian, accidents
      in developing countries.

PMID- 23860068
TI  - Management of congenital bladder diverticulum in children: A report of seven
      cases.
AB  - BACKGROUND: The purpose of the study is to present the author's experience with
      congenital bladder diverticula in seven pediatric patients at a developing world
      tertiary care center. MATERIALS AND METHODS: Records of seven patients diagnosed
      and treated as congenital bladder diverticulum, from January 1998 to December
      2009 were retrospectively reviewed for age, sex, clinical symptoms, investigative
      work-up, operative notes, and postoperative follow-up. RESULTS: All patients were
      males. Age at presentation ranged from six months to six years (mean three years
      and six months). All were manifested postnatally by urinary tract infection in
      four cases, bladder retention in three cases and abdominal pain in two cases.
      Diagnosis was suggested by ultrasound and confirmed by voiding cystourethrography
      (VCUG) in all cases and urethrocystoscopy in three cases. Open surgical excision
      of diverticulum was done in all the patients associated with ureteral
      reimplantation in four patients with VCUG-documented high-grade vesicoureteral
      reflux (VUR). Average follow-up was four years; there is a resolution of symptoms
      and no diverticulum recurrence at the defined mean follow-up. CONCLUSION:
      Recurrent urinary tract infections and voiding dysfunction in pediatric
      population should always be evaluated for congenital bladder diverticulum.
      Investigations such as abdominal ultrasound, VCUG and nuclear renal scanning,
      form an important part of preoperative diagnostic work-up and postoperative
      follow up. Diverticulectomy with ureteral reimplantation in case of high-grade
      reflux, provides good results without recurrence.

PMID- 23860069
TI  - Histopathological examination of the prepuce after circumcision: Is it a waste of
      resources?
AB  - BACKGROUND: The aim of this article is to evaluate the histopathological findings
      of foreskin after circumcision for medical indications and to find out if
      analyzing the biopsy is a waste of resources. MATERIAL AND METHODS: This
      retrospective analysis was carried out of the medical records and
      histopathological findings of 112 boys who underwent circumcision from June 2002
      to June 2005. The study group consisted of 52 boys that were circumcised for
      medical indications, while the control group consisted of 60 boys who underwent
      circumcision for religious belief. RESULTS: The mean (range) age of children in
      the study group was six (2-12) years. 36 boys had phimosis, 15 had recurrent
      balanoposthitis and one had paraphimosis as an indication for circumcision.
      Balanitis xerotica obliterans (BXO) was diagnosed in eight out of 52 biopsies
      (15%). In five of the eight BXO, the histopathological examination revealed focal
      lichenoid infiltrate which was considered as early form of BXO. There was no
      suspicion of BXO in the physical examination of those five patients. Chronic
      inflammation was reported in seven patients, while minor changes in the form of
      minimal inflammation and oedema were found in another 15 patients. The rest of
      the biopsies (22 patients) showed normal preputial pathology. The
      histopathological examinations of the control group revealed chronic inflammation
      in three patients and acute inflammation with cellular oedema in another three
      patients. CONCLUSIONS: There is a place for routine biopsy after circumcision for
      medical indications. The clinical examination failed to suspect 5 of the 8 cases
      of BXO that were diagnosed by histopathology.

PMID- 23860070
TI  - Single-layer closure of typhoid enteric perforation: Our experience.
AB  - BACKGROUND: Typhoid enteritis is rare in developed countries. The increasing
      prevalence of typhoid fever with enteric perforation in our environment is
      alarming. Peritonitis follows enteric perforation due to typhoid enteritis.
      Surgical treatments and repair of the perforated areas due to typhoid enteritis
      varies between institutions with high mortality and morbidity. MATERIALS AND
      METHODS: We retrospectively studied the effects of single versus double layer
      intestinal closure after typhoid enteric perforation with peritonitis in 902
      pediatric patients from September 2007 to April 2012. All the patients underwent
      laparotomy after resuscitation and antibiotic cover. The patients were divided
      into two groups: group A (n = 454) double layer closure and group B (n = 448)
      single layer closure. RESULTS: There were 554 males and 348 females with male to
      female ratio 1.6:1. Ages of the patients were three years to 14 years with mean
      age at eight years and mode at nine years. The following clinical outcomes were
      recorded: burst abdomen 38 (8.3%) vs 3 (0.6%), enterocutaneous fistula formation
      52 (11.4%) vs 8 (1.7%), superficial wound infection 215 (47.3%) vs 91 (20.3%),
      ligature fistula 13 (2.8%) vs 7 (1.5%), mean length of 29.4 +/- 7.8 vs 45.3 +/-
      11.6. CONCLUSION: Our results showed that single layer closure of the perforated
      ileum due to typhoid enteric perforation with peritonitis in children was
      effective by reducing complication rates.

PMID- 23860071
TI  - Pattern of paediatric trauma in Sokoto, North West Nigeria.
AB  - BACKGROUND: Paediatric trauma has become a major cause of mortality, disability
      and socioeconomic burden in developing countries and the World Health
      Organization (WHO) projects that by 2020 it will be the leading disease globally.
      This study described the pattern of paediatric injuries seen at a regional trauma
      center in North West, Nigeria. SETTINGS AND DESIGN: Trauma centre of a tertiary
      hospital in North-Western Nigeria. MATERIALS AND METHODS: A retrospective look at
      the trauma register for records of paediatric trauma from January to December
      2010 was performed. Information obtained include age and sex, causes and pattern
      of injury. The limit of 16 years was set for paediatric in our centre. RESULTS:
      The numbers of paediatric trauma seen over the 12-month period were 567 out of a
      total of 3984 trauma cases representing 14.2%. The number of males was 407(71.8%)
      and females were 160(28.2%) with M: F ratio of 2.5:1. The mean age was 7.77 and
      standard deviation of 0.19. Road Traffic Accidents (RTA) and Domestic injuries
      representing 44.8 and 42.0%, respectively, were the commonest causes of injuries.
      Laceration and bruises, head injuries including extremities were the commonest
      types of injuries seen. CONCLUSION: Road traffic accidents and domestic injuries
      as common causes of paediatric trauma need to be 'addressed by the authorities'
      so as to reduce the burden of trauma on the vulnerable children in our society.

PMID- 23860072
TI  - Testicular tumours in prepubertal children: About eight cases.
AB  - BACKGROUND: To analyze the spectrum of testicular tumors in prepubertal children
      and the therapeutic resultants in an unselected population. MATERIALS AND
      METHODS: Our hospital database was analyzed for testicular tumors from January
      1995 to December 2010 concerning clinical presentation, treatment and therapeutic
      results. RESULTS: Eight patients were operated on because of testicular tumors.
      In six cases (75%) the tumor was benign: benign teratoma (four cases), epidermoid
      cyst (one case) and immature teratoma (one case). Two patients (25%) had a
      malignant tumour: yolk-sac tumour (two cases). All this children underwent
      surgery. Radical inguinal orchidectomy was performed in six cases and
      conservative surgery was performed in two cases. One patient has received
      adjuvant chemotherapy. Follow-up was uneventfully three years after primary
      surgery. CONCLUSION: In prepubertal children, most testicular tumours are benign.
      If tumour markers were negative testis-preserving surgery can be proposed,
      complete excision of the tumour should be ascertained. In the case of testicular
      teratoma, the possibility of contralateral tumour should be considered in the
      follow-up.

PMID- 23860073
TI  - Omental cyst presenting with profound anaemia.
AB  - A male infant presented acutely with profound anaemia and abdominal distension.
      At laparotomy, a huge omental cyst was found. We reviewed our experience of this
      rare cause of abdominal pathology identifying five further cases since 2005, with
      a variety of presentations. The optimal treatment, complete resection, is
      associated with a low morbidity. The presentation with profound anaemia and shock
      due to haemorrhage into the cyst is unusual. 

PMID- 23860074
TI  - Unusual case of congenital/infantile fibrosarcoma in a new born.
AB  - Congenital infantile fibrosarcoma (CIFS) is a rare mesenchymal tumor that is
      primarily developed in the soft tissue of distal extremities and occasionally in
      unusual locations such as the lung and retroperitoneum. It occurs mainly in
      children below the age of 5 years. About 200 cases have been reported in the
      literature so far, very few of them in new-borns. The prognosis of this tumor is
      relatively good compared to adult forms. We report an unusual case of CIFS
      occurring in new-born mimicking an hemangioma and causing hemorrhage in the
      neonatal period. The tumor is located in the left arm and axilla and associated
      with a hand malformation. A shoulder amputation is performed after chemotherapy
      failure. The infant is now two-years old with no recurrence. 

PMID- 23860075
TI  - Early abdomino-perineal pull-through vaginoplasty.
AB  - Vaginal agenesis is known as one of the Mullerian anomalies. Mullerian anomalies
      occur during gonadal development and differentiation, and may lead to complex
      outcomes. McKusick-Kaufman syndrome (MKS) is an autosomal recessive multiple
      malformation syndrome characterized by Mullerian anomalies with hydrometrocolpos
      (HMC) and postaxial polydactyly (PAP). We report a case of a female newborn that
      developed hydronephrosis and respiratory distress due to compression of the
      cystic mass and underwent surgery on postpartum day 3. Pull-through vaginoplasty
      was performed with an abdomino-perineal approach. We report the unique treatment
      approach in this case.

PMID- 23860076
TI  - Pyloric atresia: A report of ten patients.
AB  - Pyloric atresia (PA) is uncommon. It occurs in 1:100000 live births. Neonates
      usually present soon after birth with copious non-bilious vomiting. The treatment
      is surgical and its prognosis is poor, especially, when it is associated with
      epidermolysis bullosa (EB). The aim of this study was to evaluate the clinical
      presentation, diagnosis, operative management, post-operative courses, and
      outcome in infant with PA, based in our cases and literature review. Charts of 10
      patients who underwent surgery for PA in the department of paediatric surgery in
      a Teaching Hospital in Tunisia (Monastir) between 1990 and 2012 were reviewed.
      Data were analysed for demographic, clinical, therapeutic, and prognostic
      characteristics. The average of age at presentation was 2 days and there were six
      males and four females. The main presenting symptoms were non-bilious vomiting in
      90% of cases. Abdominal X-ray showed gastric dilatation with an absence of gas in
      the rest of the intestinal tract in 90%, and a pneumoperitoneum in one. The
      surgical approach was laparotomy in all cases. Gastric perforation was observed
      in one patient and was completely repaired. The distribution of the anatomic
      variations was type A in nine cases and type B in one. Five patients underwent
      excision of the diaphragm and Heineke-Mikulicz pyloroplasty and
      gastroduodenostomy in the other five cases. Identified associated anomalies were
      Down's syndrome in one and EB in 2 (20%), one family has three affected sibling.
      Post-operative mortality rate was 70%. No standard surgical approach can be
      adopted a better management of PA or the associated anomalies depends on an early
      diagnosis and the availability of neonatal intensive care unit. 

PMID- 23860077
TI  - Uncorrectable coagulopathy due to intestinal obstruction: A clinical dilemma of
      competing priorities in a child.
AB  - Disseminated intravascular coagulation (DIC) is a contraindication for major
      surgical operations. However, if surgery is required to correct the underlying
      cause of DIC, a clinical conflict is created. In such complex scenario, standard
      resources such as textbooks and journals offer very little guidance. In this
      communication, we report a 22-month-old boy who developed sepsis-induced DIC
      following intestinal obstruction. Pre-operative attempts to normalize coagulation
      parameters failed. Damage control laparotomy was undertaken as it was considered
      essential to control the underlying cause of DIC. His abnormal coagulation status
      reverted quickly after surgical relief of intestinal obstruction. Paradoxically
      intraoperative blood loss was less than anticipated amount. There are a few case
      reports of adult patients who have successfully undergone major surgery despite
      the presence of abnormal coagulation. However, this appears to be the first
      paediatric report of successful surgery in DIC status. Lessons learnt from this
      case and hypothetical speculations of clinical paradoxes are discussed. 

PMID- 23860078
TI  - Repair of isolated double-chambered right ventricle.
AB  - The finding of a double-chambered right ventricle (DCRV) is exceptionally rare as
      an isolated anomaly. It is a congenital cardiac anomaly in which the right
      ventricle is separated into two chambers, a proximal high-pressure chamber and a
      distal low-pressure chamber, by anomalous muscles or fibrous tissues in the right
      ventricular cavity. We report the case of a 6-year-old infant who was admitted
      for growth retardation. The patient was diagnosed with an isolated DCRV without
      any other associated congenital anomalies. The patient underwent a successful
      cardiac surgical procedure of enlargement repair; he was discharged in good
      clinical condition with a normal cardiac function. 

PMID- 23860079
TI  - Looking beyond an abscess.

PMID- 23860080
TI  - The disorders of sex development and the problems of their management in Togo.

PMID- 23860081
TI  - Evaluation of electrospun bioresorbable scaffolds for tissue-engineered urinary
      bladder augmentation.
AB  - Tissue engineering represents a potential and valuable approach for the treatment
      of urologic pathologies. Bioresorbable polymeric scaffolds can be regarded as
      effective platforms to surgically treat bladder diseases and subsequently guide
      the formation of novel tissue after implantation. To this aim, the evaluation of
      electrospun scaffolds made up of poly(epsilon-caprolactone) blended with poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) is presented here. Firstly, the
      microstructure and the viscoelastic/mechanical properties of the electrospun
      fabrics were investigated. Then, the in vivo response was assessed by performing
      a urinary bladder augmentation using female Wistar rats as an animal model. 15
      days after the surgical procedure, the scaffolds were covered by regenerative
      urothelium up to 50%, which increased to 50-100% after 30 days. These encouraging
      results, collected in the 90-day follow-up, clearly showed the potential
      applications of tissue engineering in the urologic field. A longer in vivo
      evaluation is currently underway.

PMID- 23860083
TI  - Failure of neonatal B-cell tolerance induction by ABO-incompatible kidney grafts
      in piglets.
AB  - BACKGROUND: ABO-incompatible (ABOi) infant heart transplantation results in B
      cell tolerance to graft A/B antigens, confirming human susceptibility to acquired
      immunologic or "neonatal" tolerance as described originally in murine models.
      Starting with this clinical observation, we sought to model neonatal ABOi organ
      transplantation to allow mechanistic studies of tolerance. METHODS: Plasma anti
      A/B antibodies were measured over time in piglets to establish developmental
      antibody kinetics. Blood group O piglets received kidney allografts from group A
      (AO-incompatible) or group O (AO-compatible) donors under cyclosporine
      immunosuppression. Anti-A antibodies were measured serially after
      transplantation; A/H antigen expression and allograft rejection were assessed in
      graft biopsies. RESULTS: Anti-A antibodies developed in naive piglets in a
      kinetic pattern analogous to human infants; anti-B remained low. After
      transplantation, anti-A antibodies developed similarly in AO-incompatible and AO
      compatible groups and were not suppressed by cyclosporine. A/H antigen expression
      was persistent in all graft biopsies; however, A/H antigens were not detected in
      vascular endothelium. Cellular and antibody-mediated rejection was absent or
      minimal in early and late biopsies in both groups, with one exception.
      CONCLUSIONS: Naturally delayed isohemagglutinin production in piglets is
      analogous to the developmental kinetics in human infants. However, in contrast to
      deficient anti-A antibody production as seen long-term after "A-into-O" infant
      heart transplant recipients, normal anti-A antibody production after "A-into-O"
      piglet kidney transplantation indicates that tolerance did not develop despite
      graft A antigen persistence. These findings suggest that the impact on the host
      immune system of exposure to nonself ABH antigens during early life in human
      heart versus porcine kidney grafts may depend on expression in vascular
      endothelium.

PMID- 23860082
TI  - Efficacy of DHMEQ, a NF-kappaB inhibitor, in islet transplantation: II. Induction
      DHMEQ treatment ameliorates subsequent alloimmune responses and permits long-term
      islet allograft acceptance.
AB  - BACKGROUND: Long-term graft deterioration remains a major obstacle in the success
      of pancreatic islet transplantation (PITx). Antigen-independent inflammatory and
      innate immune responses strengthen subsequent antigen-dependent immunity;
      further, activation of nuclear factor (NF)-kappaB plays a key role during these
      responses. In this study, we tested our hypothesis that, by the inhibition of NF
      kappaB activation, the suppression of these early responses after PITx could
      facilitate graft acceptance. METHODS: Full major histocompatibility complex (MHC)
      mismatched BALB/c (H-2) mice islets were transplanted into streptozotocin-induced
      diabetic C57BL/6 (B6: H-2) mice. The NF-kappaB inhibitor
      dehydroxymethylepoxyquinomicin (DHMEQ) was administered for either 3 or 14 days
      after PITx. To some PITx recipients, tacrolimus was also administered. Islet
      allograft survival, alloimmune responses, and in vitro effects of DHMEQ on
      dendritic cells (DCs) were assessed. RESULTS: With a vehicle treatment, 600 islet
      allografts were promptly rejected after PITx. In contrast, 3-day treatment with
      DHMEQ, followed by 2-week treatment with tacrolimus, allowed permanent acceptance
      of islet allografts. The endogenous danger-signaling molecule high mobility group
      complex 1 (HMGB1) was elevated in sera shortly after PITx, whereas DHMEQ
      administration abolished this elevation. DHMEQ suppressed HMGB1-driven cellular
      activation and proinflammatory cytokine secretion in mouse bone marrow-derived
      DCs and significantly reduced the capacity of DCs to prime allogeneic T-cell
      proliferation in vitro. Finally, the DHMEQ plus tacrolimus regimen reverted the
      diabetic state with only 300 islet allografts. CONCLUSIONS: Inhibition of NF
      kappaB activation by DHMEQ shortly after PITx suppresses HMGB1, which activates
      DCs and strengthens the magnitude of alloimmune responses; this permits long-term
      islet allograft acceptance, even in case of fewer islet allografts.

PMID- 23860084
TI  - Revised Cardiac Risk Index (RCRI) is a useful tool for evaluation of
      perioperative cardiac morbidity in kidney transplant recipients.
AB  - BACKGROUND: We evaluated a published Revised Cardiac Risk Index (RCRI) to
      determine if this preoperative cardiovascular risk stratification tool would be
      useful in the kidney transplant recipient population. METHODS: We identified all
      kidney transplants from 2005 to 2009 (n=1652) at our institution. We performed a
      detailed retrospective chart review of (a) all recipients who underwent
      preoperative coronary angiography (n=169) and (b) an age-matched and
      transplantation year-matched group who did not undergo coronary angiography
      (n=156). Charts were reviewed for the presence of specific preoperative
      cardiovascular risk factors and perioperative cardiovascular complications (as
      defined by RCRI plus elevation of troponin) from time of surgery to hospital
      discharge. The total number of risk factors for each patient was compared with
      the occurrence of postoperative cardiac complications to identify a possible
      association. RESULTS: The number of risk factors was highly predictive of
      cardiovascular complications (receiver operating characteristic area, 0.77;
      P<0.0001). History of coronary artery disease was most strongly associated (odds
      ratio, 20.59; confidence interval, 4.73-89.53; P=0.0001) and history of
      congestive heart failure was also significantly associated with cardiac
      complications (odds ratio, 2.95; confidence interval, 1.01-8.59; P=0.0475).
      CONCLUSION: The RCRI is a useful tool for cardiac risk stratification in kidney
      transplantation and could be used to develop protocols for intraoperative and
      postoperative care to minimize complications.

PMID- 23860085
TI  - Prophylactic ciprofloxacin for kidney transplant recipients--to add or not to
      add.

PMID- 23860086
TI  - ABO-incompatible matching significantly enhances transplant rates in kidney
      paired donation.
AB  - BACKGROUND: Although preformed donor-specific anti-human leukocyte antigen
      antibodies (DSA) can be overcome by plasmapheresis-based strategies with some
      success in renal transplantation, kidney paired donation (KPD) is a more
      effective strategy to avoid DSA. In contrast, ABO incompatibility can be crossed
      with outcomes equivalent to ABO-compatible transplantation. Here, we report the
      ability of accepting human leukocyte antigen-compatible but ABO-incompatible
      donors to increase the number of exchanges in a KPD program. METHODS: In the
      Australian KPD program, virtual crossmatch is used to allocate suitable donors to
      recipients. Acceptance of ABO-incompatible donors is allowed in cases where anti
      blood group antibody titres are deemed amenable to removal by apheresis or
      immunoabsorption. The number of matched recipients, identified chains, and
      transplants performed with and without acceptance of ABO incompatibility was
      analyzed. RESULTS: In 2 years, 115 pairs were included in nine quarterly match
      runs. Incompatibility due to DSA accounted for 86% of the listed pairs and 52%
      were also blood group incompatible to their coregistered donor. Median calculated
      panel-reactive antibody in registered recipients was 83% (mean, 67%+/-37%). ABO
      incompatible donors were accepted for 36 patients. Two waitlist recipients and 48
      KPD candidates were matched and transplanted. Ten recipients (20%) of an ABO
      incompatible donor kidney were distributed across 8 chains that resulted in 21
      recipients being transplanted. Thus, without ABO-incompatible matching, only 27
      recipients in 12 chains would have been transplanted. CONCLUSION: Acceptance of
      blood group-incompatible donors for patients with low to moderate anti-blood
      group antibody significantly increases transplant rates for highly sensitized
      recipients.

PMID- 23860087
TI  - Extrarenal factors influencing resistance index in stable kidney transplant
      recipients.
AB  - BACKGROUND: Increased intrarenal resistance index (RI) has been associated with
      decreased long-term allograft and patient survival in kidney transplant
      recipients. Taking into account the potential role of endothelial dysfunction,
      systemic inflammation, arteriosclerotic lesions, and left ventricle remodeling,
      we performed a cross-sectional study that aimed to evaluate extrarenal factors
      that may have influence on kidney graft RI in a large cohort of stable kidney
      transplant recipients. METHODS: One hundred seventy-four kidney transplant
      recipients were enrolled into the study. Mean time after transplantation was
      8.4+/-1.8 years. Echocardiography, carotid ultrasound (intima-media thickness),
      pulse wave velocity, and Doppler examination of kidney graft were performed. The
      inflammatory markers, adhesion molecules, and plasma N-terminal prohormone of
      brain natriuretic peptide concentrations were also measured. Patients were
      divided into quartile subgroups based on RI value (Q1: RI<=0.68, Q2: RI=0.69
      0.72, Q3: RI=0.73-0.76, and Q4: RI>=0.77). RESULTS: The analyzed subgroups were
      comparable with respect to demographics (except age) and anthropometric
      parameters as well as comorbidities. The values of age, serum phosphate, pulse
      wave velocity, left ventricular mass (LVM), and LVM index (LVMI) increased in
      subsequent RI quartile subgroups. The strongest correlation was found between RI
      and age, LVM, LVMI, and plasma parathormone concentration and was negative with
      estimated glomerular filtration rate. In backward stepwise multivariate
      regression analysis, the RI variability was explained by age, LVMI, and serum
      phosphate concentration. CONCLUSION: Arterial stiffness and left ventricular
      hypertrophy may significantly influence the intrarenal vascular resistance
      measured using Doppler sonography in stable kidney transplant recipients.

PMID- 23860088
TI  - Quality of life of elderly live kidney donors.
AB  - BACKGROUND: Expanding the use of elderly live donors may help meet the demand for
      kidney transplants. The aim of this study was to quantify the effect of the
      surgical procedure on the quality of life (QOL) of elderly donors compared with
      younger donors. METHODS: Alongside three prospective studies (two randomized)
      running between May 2001 and October 2010, we asked 501 live donors to fill out
      the Short Form-36 questionnaire preoperatively and at 1, 3, 6, and 12 months
      postoperatively. We defined live donors 60 years or older as elderly. Between
      group analyses regarding QOL were adjusted for baseline values and gender.
      RESULTS: One hundred thirty-five donors were older and 366 donors were younger
      than 60 years. The response rate was high, with 87% at 12 months postoperatively.
      Elderly donors less often scored as American Society of Anaesthesiology
      classification 1 (60% vs. 81%; P<0.001) indicating a higher rate of minor
      comorbidity. At 1 month postoperatively, between-group analysis showed a
      significant advantage in QOL in favor of the elderly group regarding the
      dimensions "bodily pain" (7 points; P=0.001), "role physical" (18 points;
      P<0.001), and "vitality" (5 points; P=0.008). At 3 months, "bodily pain" (3
      points, P=0.04) and "role physical" (8 points, P=0.02) were still in favor of the
      older group. At 6 and 12 months, "physical function" was in favor of the younger
      group (3 and 5 points, respectively; P=0.04 and P<0.001). CONCLUSIONS: This study
      demonstrates that elderly donors recover relatively fast. The perspective of
      excellent postoperative QOL may help convince elderly individuals to donate.

PMID- 23860089
TI  - Blockade of NKG2D synergized with CTLA4-Ig in promoting long-term graft survival
      in murine models of cardiac transplantation: retraction.

PMID- 23860090
TI  - Companion diagnostics in oncology - current status and future aspects.
AB  - A large number of targeted anticancer drugs are currently under development and
      most of them will have a companion diagnostic linked to their use. If a
      diagnostic assay is developed in conjunction with a targeted anticancer drug,
      such an assay will later end up determining the conditions for the use of the
      drug after its approval. The assay then becomes a kind of 'gatekeeper' in
      relation to which patients should be treated with the drug in question. This
      'gatekeeper' role implies that companion diagnostic assays must live up to the
      same regulatory standards and requirements known from drug development. The
      assays must have proven to be analytically robust and reliable and to have
      demonstrated clinical utility before they are routinely used in the clinic. In
      the drug-diagnostic codevelopment model, several 'traditional' study designs have
      been used to demonstrate clinical utility. However, if we are to benefit from the
      increasing knowledge provided by molecular oncology, new ways should be developed
      to demonstrate the clinical utility of drug-diagnostic combinations. The
      development of such an approach will require a rethinking at different levels and
      is likely to include a number of ethical, regulatory and practical challenges. 

PMID- 23860091
TI  - The echocardiography "boot camp": a novel approach in pediatric cardiovascular
      imaging education.
AB  - BACKGROUND: Dynamic training schedules introduce novel challenges to medical
      specialty training programs that require manual dexterity. The aim of this study
      was to examine the effect of a 3-day, intensive pediatric echocardiography course
      ("boot camp") on trainee self-efficacy and on the acquisition and short-term
      retention of basic echocardiographic knowledge and skills for first-year
      pediatric cardiology fellows (CFs). METHODS: The boot camp consisted of hands-on
      structured practice guided by sonographers and cardiology faculty members,
      didactic lectures, and reading. Pre-boot camp experience was assessed using an
      experience score. Outcome measures included written precamp and postcamp
      examinations, a performance-based test, precamp and postcamp self-efficacy
      assessments, and the number and quality of echocardiographic examinations
      performed in the first 3 months of fellowship. RESULTS: Six CFs completed the
      boot camp. Two of the six CFs reported experience scores of 2 out of 10, whereas
      the remainder reported experience scores of 0 out of 10. Performance-based test
      scores ranged from 68 to 99 out of 147. All six CFs reported precamp self
      efficacy scores of 21 (the minimum score), compared with median postcamp scores
      of 82 (range, 49-94) (P = .01). Scores on the written examination improved from
      median of 16 (range, 11-18) to 23.5 (range, 22-28) (P = .01). CFs who completed
      the boot camp completed 28 independent echocardiographic examinations (median, 4
      per CF) during the first 3 months of fellowship, an increase from six independent
      examinations (median, 1 per CF) by CFs during the year before institution of the
      boot camp (P = .030). Echocardiograms obtained by CFs who had completed the boot
      camp scored higher on total quality (P = .004), overall two-dimensional image
      quality (P = .011), functional assessments (P = .015), and assessment for
      pericardial effusion (P = .031). CONCLUSIONS: The echocardiography boot camp
      improves self-efficacy in performing an echocardiographic examination and the
      acquisition and short-term retention of skills and knowledge required to perform
      pediatric echocardiography.

PMID- 23860092
TI  - Noninvasive assessment of pulmonary vascular resistance by Doppler
      echocardiography.
AB  - BACKGROUND: The ratio of tricuspid regurgitation velocity (TRV) to the time
      velocity integral of the right ventricular outflow tract (TVIRVOT) has been
      studied as a reliable measure to distinguish elevated from normal pulmonary
      vascular resistance (PVR). The equation TRV/TVIRVOT * 10 + 0.16 (PVRecho) has
      been shown to provide a good noninvasive estimate of PVR. However, its role in
      patients with significantly elevated PVR (> 6 Wood units [WU]) has not been
      conclusively evaluated. The aim of this study was to establish the validity of
      the TRV/TVIRVOT ratio as a correlate of PVR. The role of TRV/TVIRVOT was also
      compared with that of a new ratio, TRV(2)/TVIRVOT, in patients with markedly
      elevated PVR (>6 WU). METHODS: Data from five validation studies using
      TRV/TVIRVOT as an estimate of PVR were compared with invasive PVR measurements
      (PVRcath). Multiple linear regression analyses were generated between PVRcath and
      both TRV/TVIRVOT and TRV(2)/TVIRVOT. Both PVRecho and a new derived regression
      equation based on TRV(2)/TVIRVOT: 5.19 * TRV(2)/TVIRVOT - 0.4 (PVRecho2) were
      compared with PVRcath using Bland-Altman analysis. Logistic models were
      generated, and cutoff values for both TRV/TVIRVOT and TRV(2)/TVIRVOT were
      obtained to predict PVR > 6 WU. RESULTS: One hundred fifty patients remained in
      the final analysis. Linear regression analysis between PVRcath and TRV/TVIRVOT
      revealed a good correlation (r = 0.76, P < .0001, Z = 0.92). There was a better
      correlation between PVRcath and TRV(2)/TVIRVOT (r = 0.79, P < .0001, Z = -0.01)
      in the entire cohort as well as in patients with PVR > 6 WU. Moreover, PVRecho2
      compared better with PVRcath than PVRecho using Bland-Altman analysis in the
      entire cohort and in patients with PVR > 6 WU. TRV(2)/TVIRVOT and TRV/TVIRVOT
      both predicted PVR > 6 WU with good sensitivity and specificity. CONCLUSIONS:
      TRV/TVIRVOT is a reliable method to identify patients with elevated PVR. In
      patients with TRV/TVIRVOT > 0.275, PVR is likely > 6 WU, and PVRecho2 derived
      from TRV(2)/TVIRVOT provides an improved noninvasive estimate of PVR compared
      with PVRecho.

PMID- 23860093
TI  - Impact of telemedicine on hospital transport, length of stay, and medical
      outcomes in infants with suspected heart disease: a multicenter study.
AB  - BACKGROUND: Previous single-center studies have shown that telemedicine improves
      care in newborns with suspected heart disease. The aim of this study was to test
      the hypothesis that telemedicine would shorten time to diagnosis, prevent
      unnecessary transports, reduce length of stay, and decrease exposure to invasive
      treatments. METHODS: Nine pediatric cardiology centers entered data prospectively
      on patients aged <6 weeks, matched by gestational age, weight, and diagnosis.
      Subjects born at hospitals with and without access to telemedicine constituted
      the study group and control groups, respectively. Data from patients with mild or
      no heart disease were analyzed. RESULTS: Data were obtained for 337 matched pairs
      with mild or no heart disease. Transport to a tertiary care center (4% [n = 15]
      vs 10% [n = 32], P = .01), mean time to diagnosis (100 vs 147 min, P < .001),
      mean length of stay (1.0 vs 26 days, P = .005) and length of intensive care unit
      stay (0.96 vs 2.5 days, P = .024) were significantly less in the telemedicine
      group. Telemedicine patients were significantly farther from tertiary care
      hospitals than control subjects. The use of inotropic support and indomethacin
      was significantly less in the telemedicine group. By multivariate analysis,
      telemedicine patients were less likely to be transported (odds ratio, 0.44; 95%
      confidence interval, 0.23-0.83) and less likely to be placed on inotropic support
      (odds ratio, 0.16; 95% confidence interval, 0.10-0.28). CONCLUSIONS: Telemedicine
      shortened the time to diagnosis and significantly decreased the need for
      transport of infants with mild or no heart disease. The length of hospitalization
      and intensive care stay and use of indomethacin and inotropic support were less
      in telemedicine patients.

PMID- 23860094
TI  - Proximal isovelocity surface area by single-beat three-dimensional color Doppler
      echocardiography applied for tricuspid regurgitation quantification.
AB  - BACKGROUND: The two-dimensional (2D) proximal isovelocity surface area (PISA)
      method has known technical limitations, mainly the geometric assumptions of PISA
      shape required to calculate effective regurgitant orifice area (EROA). Recently
      developed single-beat real-time three-dimensional (3D) color Doppler imaging
      allows the direct measurement of PISA without geometric assumptions and has
      already been validated for mitral regurgitation assessment. The aim of this study
      was to apply this novel method in patients with chronic tricuspid regurgitation
      (TR). METHODS: Ninety patients with chronic TR were enrolled. EROA and
      regurgitant volume (Rvol) were assessed using transthoracic 2D and 3D PISA
      methods. Quantitative Doppler and 3D transthoracic planimetry of EROA were used
      as reference methods. RESULTS: Both EROA and Rvol assessed using the 3D PISA
      method had better correlations with the reference methods than using conventional
      2D PISA, particularly in the assessment of eccentric jets. On the basis of 3D
      planimetry-derived EROA, 35 patients had severe TR (EROA >= 0.4 cm(2)). Among
      these 35 patients, 25.7% (n = 9) were underestimated as having nonsevere TR (EROA
      <= 0.4 cm(2)) using the 2D PISA method. In contrast, the 3D PISA method had 94.3%
      agreement (33 of 35) with 3D planimetry in classifying severe TR. Good
      intraobserver and interobserver agreement for 3D PISA measurements was observed,
      with intraclass correlation coefficients of 0.92 and 0.88 respectively.
      CONCLUSIONS: TR quantification using PISA by single-beat real-time 3D color
      Doppler echocardiography is feasible in the clinical setting and more accurate
      than the conventional 2D PISA method.

PMID- 23860095
TI  - Strain analysis during exercise in patients with left ventricular hypertrophy:
      impact of etiology.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) and aortic stenosis (AS) may
      influence left ventricular (LV) systolic function, despite preservation of LV
      ejection fraction. The aim of this study was to determine the relative importance
      of cardiac afterload and myocardial hypertrophy in the potential dysfunction of
      myocardial deformation, at rest and during standardized exercise. METHODS:
      Patients with moderate to severe (<= 1.5 cm(2)) asymptomatic AS and patients with
      HCM in sinus rhythm were prospectively studied using resting and exercise
      echocardiography during submaximal exercise. Myocardial deformations were
      assessed using two-dimensional strain. Exclusion criteria were altered LV
      ejection fraction (<50%), coronary artery disease, intra-LV obstruction > 30 mm
      Hg at rest, diastolic LV thickness >= 30 mm, and New York Heart Association class
      > II. Thus, 50 patients (25 with AS, 25 with HCM) were selected and matched for
      age, sex, rest and exercise blood pressure, degree of LV hypertrophy (defined by
      maximal wall thickness), and LV ejection fraction. RESULTS: Mean resting global
      longitudinal strain (GLS) was -14.9 +/- 4.7% in patients with AS and -16.1 +/-
      3.9% in those with HCM (P = .30). During exercise (mean heart rate, 110 +/- 10
      beats/min), mean GLS was -13.9 +/- 4.2% in patients with AS and -18.1 +/- 5.4% in
      those with HCM (P = .004). GLS decreased in patients with AS but increased in
      those with HCM (DeltaGLS, 0.9 +/- 3.1% and -1.9 +/- 3.2%, respectively, P =
      .003). The same results were observed for global circumferential strain. Mean
      resting global circumferential strain was -16.4 +/- 5.8% in patients with AS and 
      17.9 +/- 4.5% in those with HCM (P = .36). During exercise, mean global
      circumferential strain was -13.8 +/- 4.1% in patients with AS and -18.6 +/- 5.3%
      in those with HCM (P = .011). Afterload was higher, particularly during exercise,
      in patients with AS than in those with HCM. CONCLUSIONS: Longitudinal and
      circumferential LV deformation during exercise was lower in patients with AS
      compared with those with HCM, despite similar resting characteristics. The
      greater afterload observed in patients with AS led to reduced contractile
      reserve.

PMID- 23860096
TI  - Left atrial function by two-dimensional speckle-tracking echocardiography in
      patients with severe organic mitral regurgitation: association with guidelines
      based surgical indication and postoperative (long-term) survival.
AB  - BACKGROUND: Left atrial (LA) mechanics in patients with severe mitral
      regurgitation (MR) remain largely unexplored. The aim of the present evaluation
      was to assess the effect of severe MR on LA function, its potential relation with
      conventional surgical indications, and long-term postoperative survival. METHODS:
      Two-dimensional speckle-tracking strain and volumetric indices of LA reservoir,
      conduit, and contractile function were assessed in 121 patients with severe MR
      and 70 controls. Patients were divided according to the presence (n = 46) or
      absence (n = 75) of one or more guidelines-based criteria for mitral surgery
      (symptoms, left ventricular ejection fraction <= 60%, left ventricular end
      systolic diameter >= 40 mm, atrial fibrillation, or systolic pulmonary arterial
      pressure >50 mm Hg). RESULTS: In patients with severe MR compared with controls,
      significant LA reservoir and contractile dysfunction was observed, which was more
      pronounced in patients with mitral surgery indication (P < .05 for all strain and
      volumetric indices). Of all indices of LA function, LA reservoir strain was an
      independent predictor (odds ratio, 0.88; 95% confidence interval, 0.82-0.94; P <
      .001) and had the highest accuracy to identify patients with indications for
      mitral surgery (area under the receiver operating characteristic curve, 0.8; 95%
      confidence interval, 0.72-0.87). A total of 117 patients underwent mitral valve
      surgery. Patients with LA reservoir strain <=24% showed worse survival at a
      median of 6.4 years (interquartile range, 4.7-8.7 years) after mitral surgery (P
      = .02), regardless the symptomatic status before surgery. LA reservoir strain, on
      top of mitral surgery indications, provided incremental predictive value for
      postoperative survival. CONCLUSIONS: Impaired LA reservoir strain in patients
      with severe organic MR relates to long-term survival after mitral valve surgery,
      independently of and incremental to current guidelines-based indications for
      mitral surgery.

PMID- 23860097
TI  - Noninvasive assessment of vascular function and hydraulic power and efficiency in
      pediatric Fontan patients.
AB  - BACKGROUND: Invasive studies have shown that children with Fontan palliation have
      abnormal arterial stiffness, impedance, and hydraulic power and efficiency. The
      aim of this study was to assess these indexes noninvasively in a cohort of
      children with Fontan circulation using Doppler echocardiography and compare their
      results with those of healthy peers. METHODS: This was a case-control study of 22
      Fontan patients and 31 healthy control children. Using standard two-dimensional,
      M-mode, and Doppler echocardiographic imaging and carotid artery applanation
      tonometry, aortic flows, dimensions, and pulse-wave velocity were measured, and
      vascular impedance and arterial stiffness were calculated. Hydraulic power and
      efficiency were calculated from standard fluid dynamics formulae. RESULTS: The
      median age was similar between groups. Stroke volume index (39 vs 39 mL/min/m(2))
      and cardiac index (2.6 vs 2.5 L/min/m(2)) were similar. Aortic cross-sectional
      area (3.3 vs 2.8 cm(2)), peak aortic flow (302 vs 261 cm(3)/sec), and myocardial
      performance index (0.47 vs 0.25) were higher and ejection fraction (50% vs 66%)
      was lower in Fontan patients. Input impedance (61 vs 83 dyne . sec/cm(5)/m(2))
      was lower in Fontan patients. Pulse-wave velocity (488 vs 364 cm/sec), elastic
      pressure-strain modulus (305 vs 263 torr), and stiffness index (4.15 vs 3.04)
      were higher in Fontan patients. Total arterial compliance (1.29 vs 1.32
      mL/torr/m(2)) and mean power (606 vs 527 mW/m(2)) were similar and total
      hydraulic power (716 vs 627 mW/m(2)) was higher in Fontan patients. Efficiency
      and the power cost per unit of forward flow were similar. CONCLUSIONS: Despite
      stiffer aortas, Fontan patients generate more hydraulic power associated with
      decreased ventricular function to achieve a similar hydraulic efficiency. In
      Fontan patients, therapy that is given to improve ventricular function may need
      to target vascular stiffness as well. This technique may be used to monitor the
      efficacy of therapeutic interventions.

PMID- 23860098
TI  - Noninvasive evaluation of right atrial pressure.
AB  - In current practice, right atrial pressure (RAP) is an essential component in the
      hemodynamic assessment of patients and a requisite for the noninvasive estimation
      of the pulmonary artery pressures. RAP provides an estimation of intravascular
      volume, which is a critical component for optimal patient care and management.
      Increased RAP is associated with adverse outcomes and is independently related to
      all-cause mortality in patients with cardiovascular disease. Although the gold
      standard for RAP evaluation is invasive monitoring, various techniques are
      available for the noninvasive evaluation of RAP. Various echocardiographic
      methods have been suggested for the evaluation of RAP, consisting of indices
      obtained from the inferior vena cava, systemic and hepatic veins, tissue Doppler
      parameters, and right atrial dimensions. Because the noninvasive evaluation of
      RAP involves indirect measurements, multiple factors must be taken into account
      to provide the most accurate estimate of RAP. The authors review the data
      supporting current guidelines, identifying areas of agreement, conflict,
      limitation, and uncertainty. 

PMID- 23860100
TI  - Family child care providers' self-perceived role in obesity prevention: working
      with children, parents, and external influences.
AB  - OBJECTIVE: To describe the perspective and strategies of family child care
      providers (FCCPs) to reduce children's suboptimal weight trajectories. DESIGN: In
      person, in-depth interviews with FCCPs. SETTING: Family child care homes.
      PARTICIPANTS: Seventeen FCCPs caring for children 6 weeks to 9 years old; 94%
      caring for children paying with a state subsidy. PHENOMENON OF INTEREST:
      Strategies of FCCP to reduce children's suboptimal weight trajectories. ANALYSIS:
      Constant comparative method of qualitative data analysis. RESULTS: Family child
      care providers described 3 core strategies: (1) improving children's behavior,
      (2) engaging and educating parents, and (3) leveraging influences external to
      their relationship with parents to effect positive change and to avoid parental
      conflict. These strategies were framed within their knowledge of child
      development, parental communication, and community services. CONCLUSIONS AND
      IMPLICATIONS: The findings suggest that FCCPs' role in obesity prevention may be
      framed within knowledge that may be commonly expected of a child care provider.
      Partnerships between public health policy makers and FCCP may reduce obesigenic
      environments by employing training and resources that link obesity prevention and
      child care provider expertise.

PMID- 23860099
TI  - Structural modulation of gut microbiota in life-long calorie-restricted mice.
AB  - Calorie restriction has been regarded as the only experimental regimen that can
      effectively lengthen lifespan in various animal models, but the actual mechanism
      remains controversial. The gut microbiota has been shown to have a pivotal role
      in host health, and its structure is mostly shaped by diet. Here we show that
      life-long calorie restriction on both high-fat or low-fat diet, but not voluntary
      exercise, significantly changes the overall structure of the gut microbiota of
      C57BL/6 J mice. Calorie restriction enriches phylotypes positively correlated
      with lifespan, for example, the genus Lactobacillus on low-fat diet, and reduces
      phylotypes negatively correlated with lifespan. These calorie restriction-induced
      changes in the gut microbiota are concomitant with significantly reduced serum
      levels of lipopolysaccharide-binding protein, suggesting that animals under
      calorie restriction can establish a structurally balanced architecture of gut
      microbiota that may exert a health benefit to the host via reduction of antigen
      load from the gut. 

PMID- 23860101
TI  - Feeding style differences in food parenting practices associated with fruit and
      vegetable intake in children from low-income families.
AB  - OBJECTIVE: To examine the moderating effects of feeding styles on the
      relationship between food parenting practices and fruit and vegetable (F & V)
      intake in low-income families with preschool-aged children. DESIGN: Focus group
      meetings with Head Start parents were conducted by using the nominal group
      technique. Parents completed information on food parenting practices and feeding
      styles. Three dietary recalls were collected on each child. SETTING: Parents
      completed measures in Head Start centers and/or over the telephone. PARTICIPANTS:
      667 parents of preschool-aged children participated. OUTCOMES: Food parenting
      practices and F & V intake. ANALYSIS: Mean differences in the food parenting
      practices across the 4 feeding styles were established through multivariate
      general linear modeling using MANOVA. Moderated multiple regression analysis was
      conducted to examine the moderating role of feeding style on food parenting
      practices and child F & V intake. RESULTS: The indulgent feeding style moderated
      the relationship between food parenting practices and child F & V intake.
      CONCLUSIONS AND IMPLICATIONS: This study indicates that parents' feeding styles
      have a moderating effect on the relationship between the food parenting practices
      and children's F & V intake. This finding can facilitate the development of
      interventions aimed at reducing childhood overweight.

PMID- 23860102
TI  - Healthy characters? An investigation of marketing practices in children's food
      advertising.
AB  - OBJECTIVE: To determine the nutritional quality of foods advertised with familiar
      children's characters and health-related messages. DESIGN: Children's programming
      aired on the most popular broadcast and cable channels during 2011 was sampled to
      form a composite weekday and weekend day. All food advertisements (ads) included
      in this programming were content analyzed. PARTICIPANTS: Five hundred seventy
      seven food ads. VARIABLES MEASURED: Familiar characters promoting products were
      either trade or licensed characters. A product's nutritional quality was
      determined using the United States Department of Health and Human Services'
      categorizations, based on the frequency foods should be consumed. Health cues
      were present when a food was claimed to be healthy, physical activity was
      depicted, or the product was associated with fruit. ANALYSIS: Frequencies and chi
      square analyses were conducted; P < .05. RESULTS: Nearly three quarters (73%) of
      food ads targeting children use a familiar character. The majority of these ads
      (72%) promote foods of low nutritional quality, yet 53% employ a health-related
      message. CONCLUSIONS AND IMPLICATIONS: Familiar characters proliferate in food
      advertising to children, yet marketers do not adhere to recommendations that
      characters promote strictly healthy foods. Future research is needed to
      investigate effects and inform policy decisions in this realm.

PMID- 23860103
TI  - A novel plantar stimulation technology for improving protective sensation and
      postural control in patients with diabetic peripheral neuropathy: a double
      blinded, randomized study.
AB  - BACKGROUND: Many diabetes-related peripheral neuropathy (DPN) patients also
      experience postural instability. OBJECTIVE: This study examined the effect of
      electrical stimulation therapy on DPN patients' postural control as well as
      recovery of plantar sensation. METHODS: 54 patients with mild to moderate DPN
      were enrolled into this study evaluating treatment of DPN with electrical
      stimulation provided via aqueous solution. The subjects were randomized into
      either sham or active stimulation. Treatments were administered 5 times per week
      for 6 weeks. Changes in neuropathy severity were assessed via Semmes-Weinstein
      monofilament tests and vibration perception threshold (VPT) tests. The potential
      benefit in postural control was assessed in a subsample of 13 subjects by
      measuring the area of center of mass (COM) sway. RESULTS: The active group saw a
      significant (p < 0.05) improvement in VPT at treatment week 6 in comparison to
      the sham group. The difference did not remain significant at follow-up visits.
      There were no significant differences between groups for the Semmes-Weinstein
      monofilament test. However, time was a significant main effect, with both groups
      improving over the course of the study. The area of COM sway was significantly
      reduced on average by 36% at treatment week 2 compared to the baseline. Although
      at treatment week 6 an additional 7% reduction in COM sway was observed compared
      to treatment week 2, the improvement from treatment week 2 to treatment week 6
      was not significant (p > 0.6). Interestingly, no significant difference was
      observed in the sham group during the study (p > 0.7). CONCLUSION: This
      randomized pilot study provides preliminary data on the potential of electrical
      stimulation via aqueous solution to improve protective sensation and postural
      stability in DPN patients.

PMID- 23860104
TI  - [Multimorbidity and multi-target therapy in phytotherapy].

PMID- 23860105
TI  - The Tibetan herbal formula Padma Digestin in functional dyspepsia: an open-label
      study.
AB  - BACKGROUND: The etiology of functional dyspepsia (FD) is multi-factorial. Its
      prevalence is high and it considerably impairs the patients' quality of life. The
      treatment options are limited. Padma Digestin, a multi-herbal formula from
      Tibetan Medicine, is traditionally used in malabsorption and dyspeptic symptoms
      as they do occur in FD, but as yet no clinical data exist on the formula. The aim
      of this study was to evaluate the safety, tolerability, and efficacy of Padma
      Digestin in patients with FD in a prospective, open, clinical phase III trial.
      PATIENTS AND METHODS: Patients were recruited by general practitioners,
      internists, and gastroenterologists and treated with 2 * 3 capsules of Padma
      Digestin daily for 6 weeks. Dyspeptic symptoms were analyzed using the
      Domestic/International Gastroenterology Surveillance Study (DIGEST) questionnaire
      extended by the 2 symptoms stomach cramps and lack of appetite. The quality of
      life was assessed using the Psychological General Well-Being Index (PGWBI-S)
      questionnaire (short version). RESULTS: 37 patients were admitted and efficacy
      could be assessed in 31. In the overall efficacy assessment, the Padma Digestin
      treatment led to a statistically highly significant reduction of the respective
      most bothersome symptom scores regarding frequency, severity, and impairment of
      daily activities (p < 0.01). The treatment also led to significant improvements
      of the individual symptoms of postprandial fullness, nausea, localized and
      diffuse epigastric pain, stomach cramps, and lack of appetite. The onset of
      improvement was after a median of 7 days; time until disappearance of the
      symptoms was after a median of 22 days. The global efficacy and tolerability were
      rated as good or very good by the doctors and the patients in 84% and 78%,
      respectively. The PGWBI-S increased from 55 +/- 19.5% to 70.5 +/- 15.5%, which is
      nearly the normal value (73.5 +/- 15.4%). As for safety, 11 patients reported a
      total of 17 adverse events (AE), 1 of which was serious but unrelated to the
      study medication. The AE were mild or moderate. The safety laboratory data showed
      no statistically significant or otherwise relevant changes. CONCLUSIONS: The
      results show that the formula Padma Digestin has a high tolerability and efficacy
      in FD symptoms and positively influences psychological well-being and thus
      quality of life. It therefore represents a much needed extension of the
      therapeutic repertoire in FD.

PMID- 23860106
TI  - [The Tibetan formula Padma Lax in medical practice: a retrospective case series
      study in constipation including 174 patients].
AB  - BACKGROUND: The Tibetan Medicine Padma Lax has been approved in Switzerland for
      the treatment of constipation and bloating for over 40 years. In this study, data
      on the application in medical practice, as well as on effectiveness in various
      constipation-related symptoms and on safety and tolerability, were collected and
      assessed. MATERIAL AND METHODS: Physicians practicing in Switzerland documented
      retrospectively the course of treatment for chronic constipation, using an
      especially developed questionnaire. In addition to defecation frequency, data on
      the intensity of 12 specific symptoms of constipation were collected. RESULTS: 17
      participating physicians provided data from a total of 174 patient cases, about
      30% of which originated from gynecological practices. Among others, lifestyle
      factors and various underlying diseases, e.g. neurological or hormonal
      disturbances, were indicated as causes of the constipation. Safety and
      tolerability were very good; only 1 adverse event (a worsening of flatulence) was
      reported. The frequency of defecation increased significantly during treatment
      and 97% reached a frequency of >2 per week. On average, the frequency and
      intensity of all symptoms decreased, with the exception of the symptom soft/loose
      stools, which increased in as many patients as it decreased. The overall
      intensity of all symptoms decreased from a mean of 15.8 by 63% to 5.8. The
      proportion of patients with severe complaints (overall intensity score >20)
      decreased from 20.1% to 1.7%, and as a result, the group with hardly any
      complaints (overall intensity score <= 5) rose from 1.2% to 57%. 86% of the
      physicians and the patients rated the efficacy as good. CONCLUSIONS: Padma Lax
      was used in constipation of different causes and in a broad spectrum of patients.
      Efficacy and safety were assessed as good or very good. In spite of the
      limitation of the retrospective study design, the data indicate that Padma Lax is
      an effective and well-tolerated treatment option for chronic constipation from
      different causes, especially also in gynecological practice, in geriatric
      patients, and in patients with neurogenic constipation.

PMID- 23860107
TI  - [Special aspects of quality of Tibetan medicines--insights from over 40 years of
      manufacturing experience in Switzerland].
AB  - Tibetan recipes are complex formulas from plant and mineral ingredients. Padma
      Inc. has been producing selected formulas from Tibetan Medicine in Switzerland
      since more than 40 years. Modern quality standards and Good Manufacturing
      Practice (GMP) guidelines are followed, ensuring the quality of the raw materials
      through the manufacturing processes to the finished product. The aim is to
      provide these valuable formulas to people in the West in a consistently high
      quality 'made in Switzerland'. The production according to modern quality
      standards is challenging, draws on many resources, and requires specialized
      expertise, e.g. in the procurement of raw materials and the quality analysis
      including pharmacognostic and botanical knowledge.

PMID- 23860108
TI  - [Clinical studies in peripheral arterial occlusive disease: update from the
      aspects of a meta-narrative review].
AB  - BACKGROUND: Atherosclerosis is a systemic disease. Its association with the
      metabolic syndrome requires a multimodal therapy setting, to alleviate symptoms
      and for primary and secondary prevention. In the planning of the therapy,
      information about evidence of the interventions and a rationale for reasonable
      combinations are important. METHOD: For compiling a meta-narrative review (MNR)
      on the evidence of complementary and conventional pharmaco-therapy in peripheral
      arterial occlusive disease (PAOD), the literature was searched for meta-analyses
      of randomized controlled trials (RCTs). These were evaluated taking into account
      network-pharmacological aspects and research parameters. RESULTS: 4 suitable meta
      analyses were found. In comparison to placebo, treatments with verum showed a
      significant improvement of the maximum walking distance of 63.5 m (95% confidence
      interval (CI) 27.11-99.91 m; Padma 28, Tibetan Formula), 41.3 m (95% CI -7.1-89.7
      m; cilostazol, phosphodiesterase IIl inhibitor), 43.8 m (95% CI 14.1-73.6 m;
      pentoxifylline, rheological drug), and 71.2 m (95% CI 13.3-129.0 m;
      naftidrofuryl, rheological drug). Only for Padma 28, clinical relevance, defined
      as an increase of the maximum walking distance by >100 m, was analyzed and
      reached by 18.2% of the verum and 2.1% of the placebo patients (odds ratio 10;
      95% CI 3.03-33.33). 1 conventional and 1 complementary drug additionally showed
      to have significant pleiotropic effects (Padma 28 and cilostazol (e.g. reduction
      of triglycerides)). CONCLUSIONS: According to meta-analytic evidence,
      naftidrofuryl and Padma 28 show clinically relevant efficacy for the treatment of
      early stages of PAOD. The extent to which the theoretically possible combination
      of different drugs contributes to improve the systemic disease under a network
      pharmacological rationale remains to be shown in a multi-armed RCT.

PMID- 23860109
TI  - [Padma 28--a useful supplement in the treatment of peripheral arterial occlusive
      disease in the stages IIa and IIb].
AB  - Peripheral arterial occlusive disease (PAOD) is in about 90% of the cases caused
      by atherosclerosis. Since this can affect all arteries of the body, PAOD is
      considered an important indicator of cardiovascular events such as heart attack
      or stroke, and thus of the leading cause of death in the Western world. With the
      measurement of the ankle/brachial pressure index (ABI), a practicable method is
      available to diagnose the disease in routine practice. Besides lifestyle
      modifications, the mainstay of treatment of atherosclerosis includes also drug
      treatment of known risk factors. In case of a severe circulatory disorder with
      critical ischemia, a revascularization by angioplasty or surgical methods is
      imperative. If the walking distance is limited due to PAOD, we speak of
      intermittent claudication. Here, in addition to the interventional treatment
      (percutaneous transluminal angioplasty (PTA) / surgery), a conservative walking
      exercise can be performed. The supportive use of Padma 28 in the conservative
      treatment has a measurable effect with a significant extension of the maximum
      walking distance and poses an additive treatment option.

PMID- 23860110
TI  - Clinical studies on the efficacy and safety of Padma 28, a complex herbal
      formulation from Tibetan medicine: an overview.
AB  - BACKGROUND: Padma 28 is an herbal formula from Tibetan Medicine, which since 35
      years has been registered in Switzerland as a drug for the symptoms of
      circulatory disorders. Over this time, a large body of scientific literature has
      accumulated. The aim of this article was to give an overview of the clinical
      studies. METHODS: A systematic literature search was done in PubMed, EMBASE, and
      the Cochrane Central Register of Controlled Trials (CCRCT). The clinical trials
      found were assessed regarding fields of application, efficacy, and safety, as
      well as methodological quality and level of evidence. RESULTS: 29 trials (1 meta
      analysis, 21 controlled trials, 7 open trials) and 3 retrospective case studies
      were found. They deal with different indications and include a total of 1,704
      verum (of these, 697 children), 333 placebo, and 394 untreated or healthy
      patients. Dropouts and withdrawals were 2.5 and 3.5 times higher in the placebo
      than in the verum group, respectively. The highest level of evidence for the use
      of Padma 28 was found in the indication of intermittent claudication (11 trials).
      Indications of efficacy were also found in other vascular (6 trials) and
      different inflammatory diseases (12 trials). CONCLUSIONS: The results suggest a
      favorable safety profile for Padma 28, also in the children examined (41% of the
      study population). Furthermore, the results show a broad field of applications.
      According to clinical evidence, Padma 28 has shown to be a safe and effective
      symptomatic treatment option for atherosclerosis-related diseases such as
      intermittent claudication. It also seems to have a potential for application in
      certain chronic inflammatory diseases such as recurrent respiratory tract
      infections, viral hepatitis, and multiple sclerosis. However, further randomized
      controlled trials (RCT) are needed to confirm these findings.

PMID- 23860111
TI  - [Periodontitis from a systemic point of view: an advanced treatment concept with
      Padma Circosan].
AB  - BACKGROUND: Periodontitis is a chronic inflammation of the periodontium, with the
      formation of bacterial biofilms in the gingival pockets. The inflammatory cascade
      is difficult to interrupt and leads to a destruction of the periodontium and bone
      loss as well as to a systemic inflammatory state. This may promote diseases such
      as atherosclerosis, diabetes, endothelial dysfunction, and cardiovascular events.
      CASE REPORT: An integrative treatment approach includes not only the treatment of
      the periodontitis (in our practice, following the Wurzburg concept) but also an
      anti-inflammatory therapy. The evaluation of data from 10 patients with chronic
      periodontitis who were additionally treated with the Tibetan Medicine Padma
      Circosan showed, after 6 months, a significant reduction in the sites with a
      probing depth of >= 4 mm (-64%) and in bleeding on probing (-87%). CONCLUSION:
      Due to its anti-inflammatory, antioxidant, and circulation-promoting effects,
      Padma Circosan is well suited for the additive treatment of periodontitis in an
      integrative therapy concept.

PMID- 23860112
TI  - [Padma 28 in cytostatic-induced dysesthesia and edema of the hands--a case from
      practice].
AB  - BACKGROUND: The herbal complex formula Padma 28 is mostly used in circulation
      induced paresthesia, in feelings of heaviness and tension in the legs and arms,
      and in numbness of the hands and feet. CASE REPORT: In the case presented here of
      a patient with breast cancer, status after full mastectomy, severe cytostatic
      induced edema, and dysesthesia occurred on both hands, which made simple, daily
      tasks impossible. Treatment with high doses of vitamin B6 was unsuccessful. Padma
      28 was given under the rationale to improve the microcirculation and thus to
      protect the delicate nerve endings. Despite ongoing chemotherapy, this treatment
      led to an improvement of the dysesthesia after 2 weeks, and after 5 weeks, the
      sensory disturbances and edema of the hands had completely disappeared.
      CONCLUSION: Padma 28 seems therefore suitable for adjuvant use in paresthesia and
      swelling caused by cytotoxic drugs during chemotherapy.

PMID- 23860113
TI  - [Tibetan formulas as pleiotropic signatures--application of network medicines in
      multimorbidity].
AB  - In the context of the network model of the organism, multimorbid states (>= 2
      chronic diseases at the same time) can be considered as a complex disease pattern
      which can be mapped as characteristic signatures. From the perspective of system
      theory, living systems such as the human body are viewed as networks of
      interacting parts. These in turn can themselves be subnetworks assigned to
      different complexity levels. They range, e.g., from the gene to the
      transcriptome, proteome, metabolome, and epigenome up to the network of the
      entire molecular interactions, the so-called interactome. In multimorbidity, the
      disease signature affects different networks at all levels, e.g., cell systems,
      organs, and functional systems. Based on this semiotics, certain signatures of
      effectiveness and profiles of action can be assigned to each drug. A drug
      signature represents the physicochemical stimuli that cause a reaction by the
      system, as well as the cross-links by which the entire connected system is
      affected at all levels. Phytotherapeutics, which chemically represent multi
      component mixtures, have especially complex signatures. As multi-target medicines
      with a pleiotropic effect profile, they therapeutically affect different levels
      of the network, which is why they are also referred to as network medicines.
      Herbal formulas from traditional medicine systems such as Tibetan Medicine are an
      example for phytotherapeutics with a particularly complex pleiotropic signature.
      Also from the traditional point of view, a disease signature is set in relation
      with a corresponding drug signature. However, in this case, it is based on the
      traditional energetic understanding of diseases. Modern research results clearly
      indicate a widely diversified signature range of Tibetan Medicines and thus
      provide a rationale for their use in integrative treatment approaches for
      diseases with complex signatures, e.g. in multimorbidity. The system-theoretical
      approach discussed here represents a method to enable a connectivity of
      traditional methods from complementary and alternative medicine to the other
      disciplines of modern medicine.

PMID- 23860114
TI  - [New approaches to elucidate the activities of botanical multi-component
      mixtures].
AB  - Although the major activities of traditional remedies have mostly been known
      since ancient times, their molecular mechanisms of action have usually not been
      investigated in much detail. The pharmaceutically relevant activities of
      botanical therapeutics frequently result from additive or synergistic effects of
      a multitude of components. Several studies have been published that analyze the
      effects of complex preparations on selected in vitro model cell systems by using
      gene expression analysis. Herein, the examples referred to include
      transcriptional studies with extracts from Ginkgo biloba and Echinacea as well as
      the Tibetan Formula Padma 28. Transcriptional profiles can be used to deduce key
      molecules and pathways affected upon treatment. Differentially expressed gene
      sets can further be integrated with information derived from interaction
      databases, thus giving a more comprehensive view of activated biological
      processes. Transcriptomics, by using microarray technology, is used as a tool in
      different fields of natural product research, ranging from activity monitoring to
      toxicity profiling.

PMID- 23860115
TI  - Clinical and histopathologic study of benign lichenoid keratosis on the face.
AB  - Benign lichenoid keratosis is a cutaneous entity that consists of a nonpruritic
      papule or slightly indurated plaque that is histologically characterized by a
      band-like inflammatory infiltrate with interface involvement. The purpose of this
      study was to investigate the clinical and histopathologic features of benign
      lichenoid keratosis localized on the face. Fourteen benign lichenoid keratosis
      patients diagnosed clinically and histopathologically in our clinic during the 10
      year period from 2002 to 2012 were studied. Thirteen female and 1 male patients
      were included. The mean age at diagnosis was 46.5 years. The color of most of the
      lesions was brown (10 cases, 71%). The cheek was the most commonly involved area
      (10 cases, 71%). All of the lesions were single. There were 9 (64%) flat lesion
      cases and 5 (36%) raised lesion cases. Most patients denied having any symptoms;
      3 had mild pruritus. The histopathological findings indicated that all the cases
      exhibited lichenoid inflammatory infiltrate obscuring the dermal-epidermal
      junction and vacuolar alteration of basal cell layer. The lesions showed focal
      parakeratosis (79%), melanophages (79%), hyperkeratosis (71%), and necrotic
      keratinocytes (71%). Solar elastosis (50%) and acanthosis (43%) were also seen
      frequently. Diagnosis of benign lichenoid keratosis should be made by a
      combination of clinical manifestations and histopathological findings. In
      particular, benign lichenoid keratosis should be considered if a middle-aged
      patient presents a solitary asymptomatic brown lesion on the face. We think
      benign lichenoid keratosis may be a specific disorder rather than the
      inflammatory stage of regressing solar lentigines, large cell acanthoma or
      reticulated seborrheic keratosis.

PMID- 23860116
TI  - Histopathologic evaluation of the sentinel lymph node for malignant melanoma: the
      unstandardized process.
AB  - Metastasis from malignant melanoma (MM) usually first presents in the draining
      lymph node basin and thus sentinel lymph node (SLN) biopsy is a staging tool used
      to predict risk of metastases and death in higher risk tumors and has become the
      standard of care. Differences in the processing and methods used in the
      histopathological examination of SLNs can affect the positivity rate for
      metastatic MM because isolated MM deposits may be small and variably distributed
      in the SLN. The examination of SLNs is not standardized. The authors surveyed
      institutions across the United States who process SLNs for MM to better
      characterize the current methods used and to suggest a standardized approach to
      improve the reliability of the SLN biopsy. A survey of 142 academic institutions
      in the United States regarding the methods used in the evaluation of the SLN
      biopsy for MM was conducted. Thirty-two institutions responded. Eighty-one
      percent of the institutions (26 of 32) had a protocol that they used for SLN
      examination. In regards to gross dissection, 28% of the responders (9 of 32)
      initially bivalve (cut the SLN in half), whereas 59% (19 of 32) use a bread loaf
      technique, cutting the SLN at even intervals without specifically commenting
      about orientation to the hilum. The number of levels initially cut from the SLN
      block varied from 1 to 8 levels per block. Thirty-nine percent of the respondents
      (12 of 31) routinely order immunohistochemistry before evaluation of the initial
      hematoxylin- and eosin-stained sections. Eighty percent of the respondents (24 of
      30) report the maximum dimension of the metastatic tumor deposit. The response
      rate was low (22%), and most respondents did not indicate how many SLN accessions
      were performed at their institution each year. Histologic protocols for
      processing SLNs for MM vary among institutions. Different methods of handling
      SLNs result in varying sensitivities for detection of metastases. Data derived
      from these varied approaches to develop and determine prognostic and staging
      categories may be inconsistent. A standardized yet practical approach is needed
      to provide reliable information on which prognosis can be determined and
      therapeutic guidelines can be based. The hope is for dermatologists and those
      treating patients with MM to understand the intricacies and inconsistencies
      involved in performance and interpretation of this key staging tool.

PMID- 23860117
TI  - Cystic verruciform xanthoma of the breast: an undescribed location of an uncommon
      lesion.

PMID- 23860118
TI  - Brain activity in using heuristic prototype to solve insightful problems.
AB  - When confronted with a real-world problem, heuristic knowledge and experience can
      guide the solution of a specific technical problem as the key step toward
      innovation. In particular, a heuristic prototype must be used correctly to cue
      the technical problem that exists in a particular situation. The present study
      selected an innovative paradigm and scientific innovation materials to
      investigate the neural basis of insight induced by heuristic prototypes using
      event-related functional magnetic resonance imaging (fMRI). The day prior to
      undergoing fMRI scanning, participants were asked to solve 42 difficult technical
      problems that scientists might have already encountered but were unknown to the
      participants. In the subsequent fMRI experiment, the same participants were
      randomly presented with 84 prototypes classified into two types: related
      prototypes (RPs), which were useful for solving previously encountered problems,
      and unrelated prototypes (UPs), which sometimes did not contribute to problem
      solving. While being scanned, participants were asked to assess whether a
      prototype is relevant to any of the technical problems. This study comprised two
      conditions: solving technical problems when presented with a related heuristic
      prototype and failing to solve technical problems using unrelated heuristic
      prototypes. The authors assumed that the regions significantly activated by the
      RP condition, compared with the UP condition, reflected brain activity related to
      the role of heuristic prototypes in scientific insight. fMRI data showed that the
      left dorsolateral prefrontal gyrus (left DLFPC, BA9) and the left angular gyrus
      (left AG, BA39) were more significantly activated when presented with RPs than
      with UPs. The results suggest that the DLPFC may be involved in the automatic
      retrieval of technical problems and breaking of mental sets. Moreover, the left
      AG may be involved in forming novel associations between technical problems and
      related prototypes. 

PMID- 23860119
TI  - Environmental enrichment in female rodents: considerations in the effects on
      behavior and biochemical markers.
AB  - Environmental enrichment (EE) exposes laboratory animals to novelty and
      complexity through alterations in the physical and social environment, which lead
      to enhanced sensory, cognitive and physical stimulation. Housing rodents in an EE
      is a highly recommended practice by governing bodies regulating animal welfare
      due to a growing body of evidence suggesting its benefits on rodents' wellbeing
      and the more naturalistic environment that such housing conditions provide.
      However, most paradigms and hypotheses rely on information currently available
      from studies performed on male subjects and the information regarding the effects
      of EE on female rodents' behavior and physiology is limited. Given the variety of
      EE paradigms described, it is increasingly difficult to ascertain the benefits or
      possible consequences of enriched housing strategies in females, let alone aid at
      establishing standardized environments in rodents. This review evaluates the
      female rodent literature that has examined the outcome of EE on behavior and
      neurochemistry and aims at identifying key elements to be addressed by future
      studies. Specifically, results from cognitive behavioral tests as well as
      commonly used tests of emotionality will be discussed, while also evaluating
      their relation to changes in neurochemistry and hormones brought on by various EE
      paradigms. Lastly, the impact of maternal enrichment on both offspring and
      maternal behavior and physiology will be reviewed. 

PMID- 23860120
TI  - Effect of insular cortex inactivation on autonomic and behavioral responses to
      acute hypoxia in conscious rats.
AB  - The present work was aimed to evaluate the contribution of interoception to the
      autonomic and behavioral responses to hypoxia. To address this issue, we studied
      whether the inactivation of the primary interoceptive posterior insular cortex
      (pIC) may disrupt the autonomic and behavioral effects of hypoxia in conscious
      rats. Rats were implanted with telemetric transmitters and microinjection
      cannulae placed bilaterally in the pIC. After one week, rats were injected with
      bupivacaine (26.5MUM 1MUL/side) and saline (1MUL/side) into the pIC, and exposed
      to hypoxia (~6% O2) for 150s, and autonomic and behavioral responses were
      recorded. Hypoxia produces hypertension, tachycardia followed by bradycardia, and
      hypothermia. When O2 dropped to ~8%, rats showed escape behavior. Baseline
      cardiovascular variables and the pattern of hypoxia-induced autonomic and
      behavioral responses were not disrupted by pIC inactivation. However, pIC
      inactivation produced a modest but significant temperature decrease, higher
      bradycardic and hypertensive responses to hypoxia, and a minimal delay in escape
      onset. In addition, we measured the hypoxia-induced Fos activation in the nucleus
      tractus solitarius (NTS), the periaqueductal gray matter (PAG) and the pIC, which
      are key components of the interoceptive pathway. Hypoxia increased the number of
      Fos-positive neurons in the NTS and PAG, but not in the pIC. Present results
      suggest that pIC is not involved in the hypoxia-induced behavioral response,
      which seems to be processed in the NTS and PAG, but has a role in the efferent
      control of autonomic changes coping with hypoxia. 

PMID- 23860121
TI  - Sgk1-dependent stimulation of cardiac Na+/H+ exchanger Nhe1 by dexamethasone.
AB  - BACKGROUND/AIMS: The serum- and glucocorticoid-inducible kinase Sgk1 contributes
      to cardiac remodeling and development of heart failure, which is paralelled by
      Sgk1-dependent stimulation of the cardiac Na(+)/H(+) exchanger Nhe1.
      Glucocorticoids are powerful stimulators of Sgk1 expression and influence cardiac
      remodeling. The present study thus explored whether the glucocorticoid receptor
      agonist dexamethasone influenced cardiac Sgk1 expression, as well as activity,
      expression and phosphorylation at Ser(703) of the cardiac Na(+)/H(+) exchanger
      Nhe1. METHODS: Experiments were performed in HL-1 cardiomyocytes and gene
      targeted mice lacking functional Sgk1 (sgk1(-/-)) and respective wild type mice
      (sgk1(+/+)). Gene expression was determined by quantitative RT-PCR and Nhe1
      phosphorylation was determined utilizing a specific antibody against a 14-3-3
      binding motif at P-Ser(703), which represents a putative phosphorylation site
      recognition motif for Sgk1 and is involved in Nhe1 activation. Cytosolic pH (pHi)
      was determined utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein
      (BCECF) fluorescence and Nhe activity by the Na(+)-dependent realkalinization
      after an ammonium pulse. RESULTS: Treatment of HL-1 cardiomyocytes with
      dexamethasone was followed by a significant increase in Sgk1 mRNA expression,
      parallelled by increased Na(+)/H(+) exchanger activity. Furthermore,
      dexamethasone significantly increased Nhe1 and Spp1 mRNA expression. The effects
      of dexamethasone were blunted by cotreatment of HL-1 cardiomyocytes with the Sgk1
      inhibitor EMD638683. Cotreatment with Nhe1 inhibitor cariporide similarly
      prevented dexamethasone-stimulated Spp1 mRNA expression. In sgk1(+/+) mice,
      dexamethasone significantly increased cardiac Sgk1 mRNA levels. In sgk1(+/+)
      mice, but not in sgk1(-/-) mice, dexamethasone significantly increased cardiac
      Nhe1 mRNA expression and Nhe1 phosphorylation at Ser(703). Furthermore, cardiac
      Spp1, Ctgf, Nppa and Nppb mRNA levels were significantly increased in
      dexamethasone treated sgk1(+/+) mice, effects significantly blunted in sgk1(-/-)
      mice. CONCLUSIONS: Sgk1 is critically involved in the phosphorylation and
      activation of the cardiac Na(+)/H(+) exchanger Nhe1.

PMID- 23860122
TI  - MLK3 promotes metabolic dysfunction induced by saturated fatty acid-enriched
      diet.
AB  - Saturated fatty acids activate the c-Jun NH2-terminal kinase (JNK) pathway,
      resulting in chronic low-grade inflammation and the development of insulin
      resistance. Mixed-lineage kinase 3 (MLK3) is a mitogen-activated protein kinase
      kinase kinase (MAP3K) that mediates JNK activation in response to saturated fatty
      acids in vitro; however, the exact mechanism for diet-induced JNK activation in
      vivo is not known. Here, we have used MLK3-deficient mice to examine the role of
      MLK3 in a saturated-fat diet model of obesity. MLK3-KO mice fed a high-fat diet
      enriched in medium-chain saturated fatty acids for 16 wk had decreased body fat
      compared with wild-type (WT) mice due to increased energy expenditure
      independently of food consumption and physical activity. Moreover, MLK3
      deficiency attenuated palmitate-induced JNK activation and M1 polarization in
      bone marrow-derived macrophages in vitro, and obesity induced JNK activation,
      macrophage infiltration into adipose tissue, and expression of proinflammatory
      cytokines in vivo. In addition, loss of MLK3 improved insulin resistance and
      decreased hepatic steatosis. Together, these data demonstrate that MLK3 promotes
      saturated fatty acid-induced JNK activation in vivo and diet-induced metabolic
      dysfunction.

PMID- 23860124
TI  - Molecular epidemiology and virulence markers of Salmonella Infantis isolated over
      25 years in Sao Paulo State, Brazil.
AB  - Infection of humans and animals caused by Salmonella is a major public health
      problem worldwide. Among the more than 2500 serovars, S. Infantis has been one of
      the 15 most isolated serovars in the world. Despite its clinical importance,
      little is known about the molecular characteristics of S. Infantis strains from
      Brazil. The aims of this study were to type S. Infantis isolates of this country
      and to assess their pathogenic potential. The molecular epidemiology of 35 S.
      Infantis strains, isolated from human sources (25) and food items (10) between
      1984 and 2009 in Sao Paulo State, Brazil, were investigated using ERIC-PCR, PFGE
      and MLST. Furthermore, the presence of some virulence markers from Salmonella
      pathogenicity islands (SPIs) SPI-1 and SPI-2 and from the virulence plasmid was
      assessed by PCR. Using ERIC-PCR, 34 S. Infantis strains exhibited a high genetic
      similarity (>= 93.7%) and using PFGE, 32 strains exhibited a similarity >= 80.6%.
      Additionally, MLST showed a high clonal similarity among strains that all
      presented the same ST32. Thirty-two isolates under investigation contained the
      virulence markers invA, sopB, sopD, sipA, sipD, ssaR, sifA, flgK, fljB and flgL.
      In conclusion, the S. Infantis strains studied were genetically similar,
      suggesting that a prevalent subtype has been causing disease and food
      contamination during a 25year period in Sao Paulo State, an important
      metropolitan region in Brazil. Furthermore, the contamination between strains
      from food items and sick humans indicates that better control measures for S.
      Infantis may be needed in this country.

PMID- 23860123
TI  - Tcf19 is a novel islet factor necessary for proliferation and survival in the INS
      1 beta-cell line.
AB  - Recently, a novel type 1 diabetes association locus was identified at human
      chromosome 6p31.3, and transcription factor 19 (TCF19) is a likely causal gene.
      Little is known about Tcf19, and we now show that it plays a role in both
      proliferation and apoptosis in insulinoma cells. Tcf19 is expressed in mouse and
      human islets, with increasing mRNA expression in nondiabetic obesity. The
      expression of Tcf19 is correlated with beta-cell mass expansion, suggesting that
      it may be a transcriptional regulator of beta-cell mass. Increasing proliferation
      and decreasing apoptotic cell death are two strategies to increase pancreatic
      beta-cell mass and prevent or delay diabetes. siRNA-mediated knockdown of Tcf19
      in the INS-1 insulinoma cell line, a beta-cell model, results in a decrease in
      proliferation and an increase in apoptosis. There was a significant reduction in
      the expression of numerous cell cycle genes from the late G1 phase through the M
      phase, and cells were arrested at the G1/S checkpoint. We also observed increased
      apoptosis and susceptibility to endoplasmic reticulum (ER) stress after Tcf19
      knockdown. There was a reduction in expression of genes important for the
      maintenance of ER homeostasis (Bip, p58(IPK), Edem1, and calreticulin) and an
      increase in proapoptotic genes (Bim, Bid, Nix, Gadd34, and Pdia2). Therefore,
      Tcf19 is necessary for both proliferation and survival and is a novel regulator
      of these pathways.

PMID- 23860126
TI  - Liquid-based cytology of the breast: pitfalls unrecognized before specific liquid
      based cytology training - proposal for a modification of the diagnostic criteria.
AB  - OBJECTIVES: To describe the pitfalls encountered in switching over from
      conventional smears (CSm) to liquid-based cytology (LBC). To explore
      modifications of our usual diagnostic criteria. STUDY DESIGN: 190 ThinPrep breast
      samples with paired biopsies were retrospectively evaluated by two breast
      cytopathologists experienced only in CSm. They were again studied after LBC
      training. The diagnostic performances were compared. In additional calculations
      we included those C4/suspicious samples containing 70% high-grade nuclei and up
      to 30% nonmalignant cells in the C5/positive category, simulating that they
      harbored a malignant one-cell population. We prospectively validated this
      modification of our diagnostic criteria. RESULTS: Training resulted in higher
      complete sensitivity: 94 versus 86% (p value 0.003) and lower false negative
      ratio: 4 versus 12% (p value 0.003). Training generated higher complete
      sensitivity than collaboration without training: 94 versus 89% (p value 0.008).
      In the simulation, the modified criteria increased absolute sensitivity to 74%
      with a 0.6% false positive rate. In the validation series, they generated up to
      91% absolute sensitivity, 12% suspicious rate and no false negative and false
      positive diagnoses. CONCLUSION: Training in breast LBC may increase diagnostic
      performance. Samples containing 70% high-grade nuclei or more can be categorized
      as malignant.

PMID- 23860125
TI  - Developmental methamphetamine exposure results in short- and long-term
      alterations in hypothalamic-pituitary-adrenal-axis-associated proteins.
AB  - Developmental exposure to methamphetamine (MA) causes long-term behavioral and
      cognitive deficits. One pathway through which MA might induce these deficits is
      by elevating glucocorticoid levels. Glucocorticoid overexposure during brain
      development can lead to long-term disruptions in the hypothalamic-pituitary
      adrenal (HPA) axis. These disruptions affect the regulation of stress responses
      and may contribute to behavioral and cognitive deficits reported following
      developmental MA exposure. Furthermore, alterations in proteins associated with
      the HPA axis, including vasopressin, oxytocin, and glucocorticoid receptors (GR),
      are correlated with disruptions in mood and cognition. We therefore hypothesized
      that early MA exposure will result in short- and long-term alterations in the
      expression of HPA axis-associated proteins. Male mice were treated with MA (5
      mg/kg daily) or saline from postnatal day (P) 11 to P20. At P20 and P90, mice
      were perfused and their brains processed for vasopressin, oxytocin, and GR
      immunoreactivity within HPA axis-associated regions. At P20, there was a
      significant decrease in the number of vasopressin-immunoreactive cells and the
      area occupied by vasopressin immunoreactivity in the paraventricular nucleus
      (PVN) of MA-treated mice, but no difference in oxytocin immunoreactivity in the
      PVN, or GR immunoreactivity in the hippocampus or PVN. In the central nucleus of
      the amygdala, the area occupied by GR immunoreactivity was decreased by MA. At
      P90, the number of vasopressin-immunoreactive cells was still decreased, but the
      area occupied by vasopressin immunoreactivity no longer differed from saline
      controls. No effects of MA were found on oxytocin or GR immunoreactivity at P90.
      Thus developmental MA exposure has short- and long-term effects on vasopressin
      immunoreactivity and short-term effects on GR immunoreactivity. 

PMID- 23860127
TI  - A container closure system that allows for greater recovery of radiolabeled
      peptide compared to the standard borosilicate glass system.
AB  - OBJECTIVES: Often peptides used in synthesis of radiopharmaceutical PET tracers
      are lipophilic and adhere to the walls of container closure systems (CCS) such
      that costly peptide and product are not fully recoverable after synthesis occurs.
      This investigation compares a standard United States Pharmacopeia (USP) Type I
      borosilicate glass CCS to a cyclic polyolefin copolymer Crystal Zenith((r)) (CZ)
      CCS, for (68)Ga-chloride and (68)Ga-DOTATOC ([(68)Ga] Ga-DOTA-D-Phe1-Tyr3
      octreotide) retention in the reaction vial after labeling. METHODS: (68)Gallium
      labeling of DOTATOC was conducted by adding (68)Ga-chloride, 2M HEPES (4-(2
      hydroxyethyl)piperazine-1-ethanesulfonic acid) or 0.75 M sodium acetate, and 1-30
      ug of DOTATOC into the CZ or glass CCS. The reaction mixture was heated for 15
      min and cooled to room temperature. The crude reaction mixture was then withdrawn
      via syringe, for final processing. The CCS was then assayed using a dose
      calibrator to determine the amount of retained (68)Ga-DOTATOC. Statistical
      significance was assessed using an unpaired Student's t-test. RESULTS: In all
      experiments (n=72) with various amounts of peptide and different buffering
      systems, the CZ CCS retained less activity than the glass CCS. Using 2 M HEPES
      and 15 ug or 30 ug of DOTATOC, the CZ CCS retained approximately 10% less of the
      labeled DOTATOC compared to the glass CCS (p<0.05). Utilizing either a sodium
      acetate or a HEPES buffering system with 15 ug or 30 ug of DOTATOC, the CZ CCS
      retained approximately 2.5% less of the total reaction activity compared to the
      glass CCS (p<0.05). Product yield was equivalent in glass and CZ CCS under the
      same reaction conditions. Both the CZ and glass vials showed no retention of
      (68)Ga-chloride. CONCLUSION: For applications involving the labeling of peptides
      such as (68)Ga-DOTATOC, the CZ CCS compared to the glass CCS, results in an
      improved recovery of product.

PMID- 23860129
TI  - Ageing of the heart reversed by youthful systemic factors!
AB  - Age-associated changes in tissue maintenance and repair have severe consequences
      to human physiology. The signals and mechanisms that cause age-related tissue
      demise are unclear. A recently published study in Cell (Loffredo et al, 2013)
      proposes that blood-borne factors in the adult systemic environment are lost
      during ageing, which leads to cardiac hypertrophy. One such factor is GDF11.
      Exposure of aged mice to youthful systemic factors or GDF11 decreases cardiac
      hypertrophy of the heart.

PMID- 23860130
TI  - Foot and ankle function after tibial overlengthening.
AB  - Lengthening the tibia more than 25% of its original length can be indicated for
      proximal femoral deficiency, poliomyelitis, or femoral infected nonunion. Such
      lengthening of the tibia can adversely affect the ankle or foot shape and
      function. The present study aimed to assess the effect of tibial lengthening of
      more than 25% of its original length on the foot and ankle shape and function
      compared with the preoperative condition. This was a retrospective study of 13
      children with severe proximal focal femoral deficiency, Aitken classification
      type D, who had undergone limb lengthening from June 2000 to June 2008 using
      Ilizarov external fixators. The techniques used in tibial lengthening included
      lengthening without intramedullary rodding and lengthening over a nail. The foot
      assessment was done preoperatively, at fixator removal, and then annually for 3
      years, documenting the range of motion and deformity of the ankle and subtalar
      joints and big toe and the navicular height, calcaneal pitch angle, and talo
      first metatarsal angle. At fixator removal, all cases showed equinocavovarus
      deformity, with decreased ankle, subtalar, and big toe motion. The mean American
      Orthopedic Foot and Ankle Society score was significantly reduced. During follow
      up, the range of motion, foot deformity, and American Orthopedic Foot and Ankle
      Society score improved, reaching nearly to the preoperative condition by 2 years
      of follow-up. The results of our study have shown that tibial overlengthening has
      an adverse effect on foot and ankle function. This effect was reversible in the
      patients included in the present study. Lengthening of more than 25% can be
      safely done after careful discussion with the patients and their families about
      the probable effects of lengthening on foot and ankle function. 

PMID- 23860128
TI  - A miR-34a-SIRT6 axis in the squamous cell differentiation network.
AB  - Squamous cell carcinomas (SCCs) are highly heterogeneous tumours, resulting from
      deranged expression of genes involved in squamous cell differentiation. Here we
      report that microRNA-34a (miR-34a) functions as a novel node in the squamous cell
      differentiation network, with SIRT6 as a critical target. miR-34a expression
      increases with keratinocyte differentiation, while it is suppressed in skin and
      oral SCCs, SCC cell lines, and aberrantly differentiating primary human
      keratinocytes (HKCs). Expression of this miRNA is restored in SCC cells, in
      parallel with differentiation, by reversion of genomic DNA methylation or wild
      type p53 expression. In normal HKCs, the pro-differentiation effects of increased
      p53 activity or UVB exposure are miR-34a-dependent, and increased miR-34a levels
      are sufficient to induce differentiation of these cells both in vitro and in
      vivo. SIRT6, a sirtuin family member not previously connected with miR-34a
      function, is a direct target of this miRNA in HKCs, and SIRT6 down-modulation is
      sufficient to reproduce the miR-34a pro-differentiation effects. The findings are
      of likely biological significance, as SIRT6 is oppositely expressed to miR-34a in
      normal keratinocytes and keratinocyte-derived tumours. 

PMID- 23860131
TI  - Glomus tumor of the great toe.
AB  - Glomus tumor is a rare mesenchymal neoplasm composed of cells that resemble the
      modified perivascular smooth muscle cells (glomus cells) of the normal glomus
      body. A glomus tumor can appear in any part of the body, although it mostly
      appears in the extremities, especially in the subungual area of the hand. It has
      been less commonly reported in the foot. A case of glomus tumor of the pulp of
      the hallux is described in the present report. 

PMID- 23860132
TI  - Locked plating of comminuted distal femur fractures: does unlocked screw
      placement affect stability and failure?
AB  - OBJECTIVES: Locked plates provide greater stiffness, possibly at the expense of
      fracture healing. The purpose of this study is to evaluate construct stiffness of
      distal femur plates as a function of unlocked screw position in cadaveric distal
      femur fractures. METHODS: Osteoporotic cadaveric femurs were used. Four
      diaphyseal bridge plate constructs were created using 13-hole distal femur
      locking plates, all with identical condylar fixation. Constructs included all
      locked (AL), all unlocked (AUL), proximal unlocked (PUL), and distally unlocked
      (DUL) groups. Constructs underwent cyclic axial loading with increasing force per
      interval. Data were gathered on axial stiffness, torsional stiffness, maximum
      torque required for 5-degree external rotation, and axial force to failure.
      RESULTS: Twenty-one specimens were divided into AL, AUL, PUL, and DUL groups.
      Axial stiffness was not significantly different between the constructs. AL and
      PUL demonstrated greater torsional stiffness, maximum torque, and force to
      failure than AUL and AL showed greater final torsional stiffness and failure
      force than DUL (P < 0.05). AL and PUL had similar axial, torsion, and failure
      measures, as did AUL and DUL constructs. All but 2 specimens fractured before
      medial gap closure during failure tests. Drop-offs on load-displacement curves
      confirmed all failures. CONCLUSIONS: Only the screw nearest the gap had
      significant effect on torsional and failure stiffness but not axial stiffness.
      Construct mechanics depended on the type of screw placed in this position. This
      screw nearest the fracture dictates working length stiffness when the working
      length itself is constant and in turn determines overall construct stiffness in
      osteoporotic bone.

PMID- 23860133
TI  - Biomechanical evaluation of interlocking lag screw design in intramedullary
      nailing of unstable pertrochanteric fractures.
AB  - OBJECTIVES: Intramedullary nails with special lag screw designs may provide
      improved mechanical performance and alleviate clinical problems. We hypothesize
      that the proximal design of trochanteric nails affects mechanical performance.
      METHODS: Ten pairs of human cadaveric femora were implanted with 2 different
      short intramedullary nails without (Gamma3) and with an interlocking lag screw
      (Intertan). An unstable, multifragmentary, pertrochanteric fracture was created.
      Bones were tested in a cyclic testing protocol with increasing loads until
      failure simulating 1 leg stance. Stiffness, failure load, cycles to failure, and
      fracture gap movements were measured. RESULTS: Initially stiffness of the
      interlocking lag screw nail was almost 40% larger (P = 0.005) compared with the
      noninterlocking nail. During the test, the difference in stiffness gradually
      decreased. Failure load (13%, P = 0.02) and cycles to failure (18%, P = 0.02)
      were larger for the interlocking nail construct. Rotation and varus collapse of
      the head were initially up to 84% lower (P = 0.013) for the interlocking
      technique. During the test, the rate of rotational instability gradually
      increased for both techniques. CONCLUSIONS: The interlocking lag screw design
      reduced movement of the femoral head and relative movement between fracture
      fragments. Beyond that the trapezoidal nail design of the Intertan reduced
      toggling within the trochanteric area and prolonged survival. Although this study
      showed a decrease in the retention of stability over time, failure did not occur
      until the equivalent of 2-3 months of reduced physical activity in which healing
      may have occurred under normal clinical conditions.

PMID- 23860134
TI  - Osteosynthesis of unstable intracapsular femoral neck fracture by dynamic locking
      plate or screw fixation: early results.
AB  - OBJECTIVES: The purpose of this study was to compare the postoperative radiologic
      and clinical outcomes of telescopic femur neck screws and small locking plate
      device (Targon FN) (group 1) with multiple cancellous screws (group 2) for
      displaced intracapsular femoral neck fractures. DESIGN: Comparison of a
      prospective collected data to a historical control group (retrospective).
      SETTING: One community teaching hospital. PATIENTS: Seventy-eight patients (group
      1, 31; group 2, 47) underwent reduction and internal fixation of displaced
      intracapsular femoral neck fractures with either Targon FN device or multiple
      cancellous screws from March 2000 to July 2010. Their mean age was 53.7 years
      (SD: 16.4), and the mean follow-up period was 28.6 months. MAIN OUTCOME MEASURES:
      Treatment failure was considered to be either a nonunion, osteonecrosis, or
      revision surgery of any type. Treatment was regarded as successful in patients
      who did not show failure and had at least 1-year follow-up. RESULTS: One patient
      in group 1 (3.2%) and 22 (46.8%) in group 2 had a nonunion (P = 0.0001). Four
      (12.9%) group 1 patients and 16 (34.0%) group 2 patients underwent revision
      surgery (P = 0.036). Four (12.9%) patients in group 1 and 4 (8.5%) group 2
      patients had osteonecrosis of the femoral head (P = 0.531). Multivariate logistic
      regression showed that internal fixation by the fixed-angle fixation device
      decreased the odds ratio for overall complication by a factor of 0.23, for
      example, by 77% (P = 0.018). CONCLUSIONS: Performing internal fixation by a fixed
      angle fixation device decreased nonunion rates and revision rates. It did not
      affect the rate of osteonecrosis. LEVEL OF EVIDENCE: Therapeutic level III. See
      instructions for authors for a complete description of levels of evidence.

PMID- 23860135
TI  - Early versus delayed operative intervention in displaced clavicle fractures.
AB  - OBJECTIVES: Recent evidence to suggest that fixation of clavicle fractures yields
      better outcomes than conservative treatments has led to an increasing trend
      toward operative management. There is no evidence, however, to compare early
      fixation with delayed fixation for symptomatic patients before union. DESIGN:
      Prospective comparative case series. SETTING: Level 1 regional trauma center.
      PATIENTS: Displaced clavicle fractures treated operatively in our institution
      during a 4-year period. Ninety-seven patients were included: 68 with early
      fixation and 29 delayed. Radiographic and clinical outcomes were available for
      all patients and scores were available for 62. INTERVENTION: Early plate fixation
      (within 3 weeks) of displaced clavicle fractures compared with delayed (3-12
      weeks) fixation of displaced clavicle fractures. OUTCOMES: Radiographic union,
      Oxford Shoulder Score, QuickDASH, EQ5D, and a patient interview. Mean follow-up
      was to 30 months. RESULTS: There were no statistically significant differences in
      age (P > 0.05), sex (P > 0.05), and energy of injury (P > 0.05) between the 2
      groups. The mean QuickDASH was 8.9 early and 9.1 delayed (P < 0.05) and the
      Oxford Shoulder Score was 44.2 early and 43.9 delayed (P < 0.05). In the early
      fixation group, there were 5 wound healing complications, and 8 went on
      subsequently to have removal of prominent metalwork. In the delayed fixation
      group, 2 had wound healing complications and 4 required removal of prominent
      metalwork. There were no statistically significant differences in the EQ5D
      scores. CONCLUSION: Our series supports delayed fixation of symptomatic clavicle
      fractures as results do not differ from early fixation. LEVEL OF EVIDENCE:
      Therapeutic Level II. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 23860137
TI  - Cerebral cavernomas and intractable epilepsy: What should be the extent of
      resection for optimal seizure outcome?

PMID- 23860136
TI  - RGD-bearing peptide-amphiphile-hydroxyapatite nanocomposite bone scaffold: an in
      vitro study.
AB  - In this study, a fibrous nanocomposite scaffold was developed by combining
      hydroxyapatite (HA) fibers produced by electrospinning method and arginine
      glycine-aspartic acid (RGD)-bearing peptide-amphiphile (PA) gel (PA-RGD) produced
      by self-assembly and gelation induced by calcium ions. Scanning electron
      microscope, transmission electron microscope and atomic force microscopy imaging
      confirmed the successful production of inorganic and organic components of this
      nanocomposite material. Within the HA, the presence of a CaCO3 phase, improving
      biodegradation, was shown by x-ray diffraction analysis. The in vitro
      effectiveness of the PA-RGD/HA scaffold was determined on MC3T3-E1 preosteoblast
      cultures in comparison with HA matrix and PA-RGD gel. The highest cellular
      proliferation was obtained on PA-RGD gel, however, alkaline phosphatase activity
      results denoted that osteogenic differentiation of the cells is more favorable on
      HA containing matrices with respect to PA-RGD itself. Microscopic observations
      revealed that all three matrices support cell attachment and proliferation.
      Moreover, cells form bridges between the HA and PA-RGD components of the
      nanocomposite scaffold, indicating the integrity of the biphasic components.
      According to the real time-polymerase chain reaction (RT-PCR) analyses, MC3T3-E1
      cells expressed significantly higher osteocalcin on all matrices. Bone
      sialoprotein (BSP) expression level is ten-fold higher on PA-RGD/HA nanocomposite
      scaffolds than that of HA and PA-RGD scaffolds and the elevated expression of BSP
      on PA-RGD/HA nanocomposite scaffolds suggested higher mineralized matrix on this
      novel scaffold. Based on the results obtained in this study, the combination of
      HA nanofibers and PA-RGD gel takes advantage of good structural integrity during
      the cell culture, besides the osteoinductive and osteoconductive properties of
      the nanofibrous scaffold.

PMID- 23860138
TI  - Complication avoidance and its management in endoscopic neurosurgery.
AB  - Endoscopic techniques are increasingly being used in recent times for various
      spinal and brain pathologies. Although endoscopic neurosurgical technique holds
      the potential for reducing morbidity, it is also associated with limitations such
      as steep learning curve, obstruction in manipulation of instruments by telescope
      in an already limited exposure, proximal blind spot, visual obscuration,
      disorientation, loss of stereoscopic image and others. Neuroendoscopy is distinct
      from micro-surgery and a thorough understanding of the technique and its
      limitations is required to get maximal benefit. Difficulties in controlling
      bleeding, longer operative time are common obstacles with this technique,
      especially in early learning curve. Higher complication rate during initial
      learning curve can be reduced by attending live workshops, practice on models and
      hands on cadaveric workshops. Large vascular lesions should be avoided and a
      thorough knowledge of possible complications and techniques to avoid such
      complications can improve results in endoscopic surgery. 

PMID- 23860139
TI  - Gluten ataxia of sporadic and hereditary cerebellar ataxia in patients from
      mainland China.
AB  - BACKGROUND: Gluten sensitivity (GS) is a spectrum of disorders with diverse
      manifestations. Recent evidence suggests that ataxia may be the only
      manifestation of GS and that it may be one of the causes of sporadic ataxia. AIM:
      To investigate the prevalence of gluten ataxia among patients with ataxia in
      China. MATERIALS AND METHODS: Serum levels of anti-gliadin, anti-transglutaminase
      2 (TG2), and anti-transglutaminase 6 (TG6) antibodies measured in 125 patients
      with ataxia (100 patients with sporadic ataxia and 25 patients with hereditary
      ataxia) and 51 healthy controls by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The serum concentrations of anti-gliadin, anti-TG2 IgG, IgA, and TG6-IgG
      antibodies were elevated in ataxia patients, but the increase was not
      statistically significant. However, TG6-IgA serum levels were significantly
      higher in sporadic ataxia as compared to those in healthy controls (P < 0.05).
      CONCLUSIONS: These results provide evidence that sporadic ataxia in a subgroup of
      patients may be due to gluten ataxia in mainland China. Measurement of serum anti
      TG6 antibodies along with anti-TG2 and anti-gliadin antibodies may be useful for
      diagnosing gluten ataxia.

PMID- 23860140
TI  - Prognostic value of magnetic resonance imaging in patients with clinically
      isolated syndrome conversion to multiple sclerosis: a meta-analysis.
AB  - BACKGROUND: Numerous studies have investigated the associations of brain or
      spinal cord MRI with the risk of developing Multiple Sclerosis (MS) in people
      with Clinically Isolated Syndrome (CIS), however, the findings are uncertain.
      Therefore, we performed a meta-analysis based on 24 publications to
      comprehensively evaluate such associations. MATERIALS AND METHODS: The databases
      of EMBASE and MEDLINE (January 1980-August 2011) were searched electronically for
      all relevant studies. Data were extracted from each study independently by both
      reviewers using a predefined structured spreadsheet. The quality of each study
      was assessed independently by two reviewers according to Newcastle-Ottawa Scale
      for reading cohort study proposed by Deeks et al. The meta-analysis including 24
      qualified studies was performed by using the Cochrane Collaborations RevMan5.0
      software. RESULTS: Twenty-four identified studies met the inclusion criteria and
      minimum quality threshold. A meta-analysis of cohort studies indicated that the
      CISs having MRI lesions did have significantly increased risk for MS (risk ratio
      [RR] = 3.71, 95% confidence interval [CI], 3.27-4.21, P < 0.00001). In the
      subgroup analysis (according to the number of T2 lesions at baseline), the risk
      of developing MS in CIS patients with the medium MRI burden (4-9 lesions) was
      higher than with the low MRI burden (1-3 lesions) (RR = 0.66,95% CI, 0.45-0.95, P
      < 0.00001). While, no correlation was found in group between the medium MRI
      burden and the high MRI burden(>9 lesions) (RR = 0.97, 95% CI, 0.82-1.15, P =
      0.72). Meanwhile, the CIS patients with abnormal baseline MRI, especially with
      infratentorial lesions, had a high risk of conversion to MS compared to patients
      without the such infratentorial lesions (RR = 1.37, % CI, 1.09-1.73, P = 0.0008).
      CONCLUSIONS: Despite some limitations, this meta-analysis established solid
      statistical evidence for an association between the presence or absence of MRI
      lesions within the brain or spinal cord MRI and the risk of developing MS,
      particularly for studies with large sample size. The CIS patients with abnormal
      baseline MRI, especially with infratentorial lesions, had a high risk of
      conversion to MS. However, this association warrants additional validation in
      larger and well designed studies.

PMID- 23860141
TI  - Are syncopes in sitting and supine positions different? Body positions and
      syncope: a study of 111 patients.
AB  - CONTEXT: Syncope is a common cause of transient loss of consciousness. In the
      analysis of patients having syncope, body position has not been systematically
      studied and correlated with triggers, prodromal symptoms and circumstances. This
      correlation is important in differentiating syncope from its mimics. AIMS: To
      study syncope with respect to body positions, triggers, prodromal symptoms and
      circumstances. SETTINGS AND DESIGN: Prospective study set in Neurology Department
      of Tertiary Care Center. MATERIALS AND METHODS: Patients fulfilling guidelines
      set by The Task Force for the Diagnosis and Management of Syncope of the European
      Society of Cardiology (ESC) were recruited. Detailed clinical history,
      examination and investigations (ECG, 2D-ECHO, Head Up Tilt Test, Holter monitor,
      EEG, MRI Brain) were carried out. RESULTS: Out of the 111 recruited patients, 67
      developed syncope in standing, 16 in sitting, 23 in both standing and sitting, 1
      in both sitting and supine and 4 in all three positions. Prodromal symptoms were
      present in 81% while triggers in 42% and circumstances in 41% of patients. Black
      out, sweating, dizziness and headache were most common prodromal symptoms.
      Intense pain, smell and fear were most common triggers while prolonged standing,
      hot crowded room and fasting were most common circumstances associated with
      syncope. CONCLUSIONS: Against common belief, syncope can occur in sitting as well
      as in supine position. Emotional triggers were commoner in patients with syncope
      in supine and sitting positions while prodromal symptoms and circumstances were
      similar for all positions. Syncope should be considered in body positions other
      than standing.

PMID- 23860142
TI  - A prospective study of in-hospital mortality and discharge outcome in spontaneous
      intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is associated with high mortality and
      morbidity. Various clinical and imaging predictors of mortality have been
      observed in previous studies. AIMS: To study factors associated with in-hospital
      mortality in patients with ICH and observe the disability status of patients
      [assessed by modified Rankin scale (mRS)] at the time of discharge. DESIGN:
      Prospective observational study. MATERIALS AND METHODS: All consecutive patients
      with acute hypertensive ICH admitted during the study period were enrolled. Data
      recorded included: Demographics, clinical, biochemical and cranial computed
      tomography (CT) findings. Primary outcome was defined as either death or survival
      within the hospital. mRS was used to assess outcome at discharge. RESULTS: Of the
      total 214 patients with ICH (193 supratentorial and 21 infratentorial), 70
      (32.7%) patients died during the hospital stay. On bivariate analysis, low
      Glasgow Coma Scale (GCS) score, ventilatory assistance, higher hematoma volume,
      midline shift, hydrocephalus and intraventricular hematoma (IVH) were associated
      with mortality. ICH grading scale (ICH-GS) and ICH scores were higher in patients
      who died (P < 0.0001). Ninety-five (44.6%) patients underwent a neurosurgical
      intervention; 66 (45.8%) patients among the survivors compared with 29 (41.4%)
      among those who died (P = 0.54, Odds Ratio (OR) 0.83, 95% Confidence Interval
      (CI) 0.46-1.48). Independent predictors of mortality included a higher baseline
      hematoma volume ( P = 0.04 OR 1.01, 95% CI 1.00-1.02), lower GCS ( P = 0.01 OR
      2.57, 95%CI 1.25-5.29), intraventricular extension of hematoma ( P = 0.007 OR
      2.66, 95% CI 1.26-5.56) and ventilatory requirement (P < 0.0001 OR 8.34, 95%CI
      2.75-25.38). Among survivors (n = 144), most were disabled [mRS 0-3, 7 (4.8%) and
      mRS 4-5, 137 (95.13%)] at discharge. CONCLUSIONS: Low GCS, higher baseline ICH
      volume, presence of IVH and need for ventilatory assistance are independent
      predictors of mortality. Most of the patients at discharge were disabled. Surgery
      did not improve mortality or outcome.

PMID- 23860143
TI  - Adiponectin receptor 1 expression is associated with carotid plaque stability.
AB  - BACKGROUND: Adiponectin is a hormone secreted exclusively by adipose tissue, and
      is important in the regulation of tissue inflammation and insulin sensitivity.
      Adiponectin exerts its effects through two cell-surface receptors: Adiponectin
      receptor 1 (ADR1) and ADR2. However, the relationship between ADR1/2 expression
      and progression of atherosclerosis or plaque vulnerability remains unclear. AIMS:
      To investigate the relationship between ADR1/2 expression and plaque
      characteristics in patients with carotid artery atherosclerosis. MATERIALS AND
      METHODS: Forty-three patients who underwent carotid endarterectomy for treatment
      of carotid artery stenosis were reviewed. Immunohistochemical staining for ADR1
      and ADR2 was performed in the specimens of carotid plaque. The relationships
      between ADR1/2 expression and clinical characteristics were analyzed
      statistically. RESULTS: Plaque was stable in 7 patients and vulnerable in 36
      patients. ADR1 expression was considered weak in 29 patients and strong in 14
      patients. The formation of vulnerable plaques was significantly correlated with
      weak ADR1 expression (P < 0.003). ADR2 expression was considered weak in 14
      patients and strong in 29 patients. Rates of formation of vulnerable plaque did
      not differ between patients with weak and strong ADR2 expression. CONCLUSIONS:
      Based on previous and the present results, ADR1 may be strongly related to the
      stabilization of established atherosclerotic plaques via inactivating
      macrophages. Enhancement of ADR1 expression could serve as a therapeutic target
      for the prevention of the formation of vulnerable plaque.

PMID- 23860144
TI  - Spectrum of congenital myopathies: a single centre experience.
AB  - BACKGROUND: Congenital myopathies (CMs) are rare and they are clinically and
      genetically heterogeneous. Muscle biopsy is characterized by structural
      abnormality that is diagnostic. There are few studies from India. MATERIALS AND
      METHODS: This is a retrospective study of 12 years. The demographic data,
      clinical features and laboratory data of patients diagnosed as CMs on muscle
      biopsy were retrieved from medical records. The slides were reviewed for
      morphological and structural abnormalities using the following stains hematoxylin
      and eosin, modified Gomori trichrome, masson trichrome, periodic acid schiff,
      adenosine triphosphatase preincubated at pH 9.4, 4.6 and 4.3, nicotinamide
      adenine dinucleotide tetrazolium reductase, succinic dehydrogenase and cytochrome
      c oxidase. Immunohistochemistry was performed with dystrophin, sarcoglycans and
      desmin wherever necessary. RESULTS: There were 50 patients with CMs:
      Centronuclear myopathy (23), myotubular myopathy (3) and central core disease
      (CCD) (8), nemaline myopathy (5), congenital fiber type proportion (10) and
      desmin related myopathy with arrythmogenic right ventricular cardiomyopathy
      (ARVD) (1). Of the 50 patients, 30 (60%) presented in the first decade of life.
      Proximal muscle weakness and hypotonia were the common presenting features. Type
      1 atrophy and predominance were seen in most cases on muscle biopsy. CCD had one
      patient with high creatine phosphokinase levels, biopsy in one patient showed
      both rods and cores, in the other limb girdle muscular dystrophy like picture and
      one biopsy showed uniform type 1 fibers. There was one desmin related myopathy
      with ARVD, who had cardiac transplantation and both skeletal and cardiac muscle
      showed characteristic rimmed vacuoles and inclusions positive for desmin.
      CONCLUSION: CMs are rare and the diagnosis can only be established on muscle
      biopsy. Defining the specific CMs helps the clinician in counseling the patient
      and family.

PMID- 23860145
TI  - Phase II trial of temozolomide plus concurrent whole-brain radiation followed by
      TNV regimen as adjuvant therapy for patients with newly diagnosed primary CNS
      lymphoma.
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive
      extranodal non-Hodgkin's lymphoma limited to the CNS. Treatment of PCNSL with
      high-dose methotrexate (HD-MTX)-based chemotherapy and whole-brain radiotherapy
      (WBRT) is associated with high rates of relapse and severe treatment-related
      neurotoxicity. AIM: To report our experience of treating newly diagnosed PCNSL
      with temozolomide, nedaplatin, and vincristine (TNV), as the replacement of HD
      MTX, in combination with concurrent chemoradiotherapy. MATERIALS AND METHODS:
      Newly diagnosed PCNSL patients were given concurrent temozolomide (75 mg/m 2 ,
      orally) daily during WBRT. Then, the TNV regimen was given after four weeks. The
      TNV regimen consisted of temozolomide (200 mg/m 2 orally: Days 1-5), nedaplatin
      (80 mg/m 2 intravenous: Day 1), and vincristine (1.4 mg/m 2 intravenous: Day 1).
      Each cycle was of a duration of four weeks and a maximum of six cycles were
      applied. The primary end point was response to treatment obtained by magnetic
      resonance imaging (MRI). Secondary end points were progression-free survival
      (PFS) and fewer toxic effects. RESULTS: The study subjects included 14 patients
      (median age: 53.5, median Karnofsky Performance Scale (KPS): 75). The median
      number of TNV cycles given was five. RESPONSE TO TREATMENT: Complete response in
      12 (85.7%) patients, partial response in 2 (14.3%) patients, and none with
      progressive disease. The objective response rate was 100%, and median PFS was
      21.4 months. Toxicity was relatively mild, which mainly included nausea in six
      and fatigue in five, grade 3-4 hematotoxicity in one, and abnormal liver
      functions in five patients. No neurotoxicity has been observed till date.
      CONCLUSION: The efficacy outcomes in this study are comparable to other reported
      HD-MTX-based regimens plus WBRT, with an added favorable toxicity profile.
      Prospective, randomized controlled trials are warranted to confirm such results.

PMID- 23860146
TI  - Parent artery occlusion with Onyx for distal aneurysms of posterior inferior
      cerebellar artery: a single-centre experience in a series of 15 patients.
AB  - BACKGROUND: Aneurysms located at distal posterior inferior cerebellar artery
      (PICA) are rare. These aneurysms are difficult for surgical or endovascular
      treatment, especially for ruptured aneurysms. AIMS: To investigate the clinical
      and radiologic efficacy of parent artery occlusion (PAO) with embolic agent Onyx
      in the treatment of distal PICA aneurysm. MATERIALS AND METHODS: Case records of
      15 consecutive patients with 15 ruptured distal PICA aneurysms treated with Onyx
      embolization were reviewed retrospectively. The follow-up ranged between 6 and 52
      months. Cerebral angiography or cerebra computed tomography-angiogram (CTA) was
      performed for follow-up radiological study. Two aneurysms had origin from
      tonsillomedullary segment, nine from telovelotonsillar segments, and four from
      cortical segments. All patients were treated with Onyx to occlude aneurysm and
      proximal portion of vessel in front of aneurysm via endovascular approach.
      RESULTS: Aneurysm was occluded completely in every patient. One patient died
      because of intra-procedure haemorrhage. Fourteen patients had good recovery and
      the last follow-up Glasgow outcome scale was 5. Head CT scan was performed in
      every survived patient before discharge. CT in 3 patients revealed cerebellar
      infarctions but without any neurological deficits. None of the 14 patients had
      rebleeding or fresh neurologic deficits during the follow-up period. Aneurysmal
      recanalization had not been observed in any of the survived patients.
      CONCLUSIONS: Onyx occlusion of proximal parent artery and aneurysm in the
      treatment of distal PICA aneurysm is safe and effective according to this study.
      Morphology and location of aneurysm are important to decide the therapeutic
      strategy.

PMID- 23860147
TI  - Unruptured intracranial aneurysms: comparison of perioperative complications,
      discharge disposition, outcome, and effect of calcification, between clipping and
      coiling: a single institution experience.
AB  - OBJECTIVE: The aim of the study was to compare the perioperative complications,
      obliteration rates, discharge dispositions, clinic-radiological outcomes, and the
      role of calcification between the microsurgical and endovascular treatment of
      unruptured intracranial aneurysms. MATERIALS AND METHODS: Retrospective data of
      the patients treated with microsurgical clipping and those treated by
      endovascular coiling from January 2007 to August 2012 was collected from the
      database. RESULTS: Intraoperative rupture was not different in both the treatment
      groups (4.05% vs. 1.5% clip vs. coil). A total of 9.4% of the patients in the
      clipping group and 4.5% of the patients in the coiling group suffered
      postoperative stroke. At last follow up, 89% of the patients in the clipping
      group and 93% of the patients in the coiling group had favorable outcomes. The
      mean length of stay was more in clipping group (6.1 vs. 2.7, clip vs. coil, P <
      0.05). Patients discharged to home without assistance/rehabilitation services
      were more in coiling ( P = 0.001). A total of 28.4% (23/81) of the coiled
      aneurysms were found to have residue neck on postoperative angiograms as compared
      with 12.6% (10/79) of the clipped aneurysms ( P = 0.01). Calcification within the
      aneurysm was strongly correlated to the size, perioperative complications, and
      the outcome ( P < 0.05). However, on excluding the calcified cases the size and
      outcome do not show a significant correlation. CONCLUSION: With appropriate
      patient selection, the majority of the UIAs can be managed by either of the
      treatment modalities with very low mortality and morbidity. Both the treatment
      modalities should be employed synergistically.

PMID- 23860148
TI  - Frame-based radiosurgery: Is it relevant in the era of IGRT?
AB  - PURPOSE: To assess the setup errors and intrafraction motion in patients treated
      with frame-based and frameless stereotactic radiosurgery (SRS). MATERIALS AND
      METHODS: Ten patients treated with frame-based and six patients treated with
      frameless radiosurgery were prospectively enrolled in the study. Leksell frame
      was used for frame-based and a customized uniframe orfit cast for frameless
      techniques. Cone beam computed tomography (CBCT) scans were taken immediately
      before and after each treatment to evaluate the positional accuracy and
      corrections applied with the use of hexapod couch for both groups. RESULTS: The
      mean translational shifts with frame-based SRS were 1.00 +/- 0.30 mm in the
      lateral direction (X), 0.20 +/- 1.20 mm in craniocaudal direction (Y) and -0.10
      +/- 0.31 mm in the anteroposterior direction (Z). The rotational shifts for frame
      based treatments were as follows: roll 0.32 +/- 0.70, pitch 0.44 +/- 0.66 and yaw
      0.20 +/- 0.4. For frameless SRS, translational shifts were -0.40 +/- 0.90, 1.10
      +/- 1.10, and 0.50 +/- 1.30 mm in X, Y, and Z directions, respectively, and
      rotational shifts were -0.11 +/- 0.78, 0.20 +/- 0.44, and 0.29 +/- 0.35 in roll,
      pitch, and yaw, respectively. Intrafraction shifts with frame-based SRS were: X =
      0.60 +/- 1.80 mm, Y = 0.20 +/- 0.60 mm, and Z = 0.00 +/- 0.05 mm; and rotational
      shifts were: roll 0.01 +/- 0.27, pitch 0.06 +/- 0.15, and yaw 0.01 +/- 0.09. For
      frameless SRS, these were: X = 0.11 +/- 0.20 mm, Y = 0.20 +/- 0.40 mm, and Z =
      0.20 +/- 0.20 mm and rotational shifts were: roll 0.09 +/- 0.23, pitch 0.00 +/-
      0.12, and yaw 0.00 +/- 0.09. CONCLUSIONS: In our experience, set up accuracy of
      frameless SRS is as good as frame-based SRS. With availability of verification
      methods such as CBCT and hexapod couch, an accurate and precise treatment
      delivery is feasible with frameless techniques.

PMID- 23860149
TI  - Treatment of a canine carotid artery aneurysm model with a biodegradable
      nanofiber-covered stent: a prospective pilot study.
AB  - AIM: To evaluate the use of a biodegradable nanofiber-covered stent (BDNCS) in
      the treatment of a canine carotid artery aneurysm. MATERIALS AND METHODS:
      Seventeen beagle dogs, each with one lateral saccular aneurysm created using a
      venous pouch, were selected to test the BDNCS. The BDNCS consists of three parts:
      A bare stent, a biodegradable nanofiber membrane, and a balloon catheter. The
      bare stent was sculpted by a laser from a cobalt chromium superalloy, and the
      biodegradable nanofiber membrane was constructed from polylactic acid (PLA) and
      polycaprolactone [PCL, P (LLA-CL)] by the electro-spinning method. The
      biodegradable nanofiber stent was premounted on a balloon catheter to form a
      BDNCS. Angiographic assessments were categorized as complete or incomplete
      occlusion. Data regarding technical success, initial and final angiographic
      results, mortality and morbidity were collected, and follow-up was performed at 1
      and 3 months after the procedure. RESULTS: BDNCS placement was successful in 17
      canines with 17 aneurysms. The initial angiographies showed that a complete
      occlusion was achieved in 13 canines (76.5%) and an incomplete occlusion in 4
      (23.5%). One canine died 1 week later. The angiographies obtained at 3-month
      follow-up exhibited complete occlusion in 14 canines (87.5%) and an incomplete
      occlusion in 2 canines, with mild in-stent stenosis in 5 canines. CONCLUSIONS:
      Our results suggest that BDNCS may be a feasible approach for aneurysm occlusion,
      although the occurrence of mild in-stent stenosis was relatively high. Longer
      term follow-up investigations are needed to validate these findings.

PMID- 23860150
TI  - Extended resection of hemosiderin fringe is better for seizure outcome: a study
      in patients with cavernous malformation associated with refractory epilepsy.
AB  - BACKGROUND: Cerebral cavernous malformation (CCM) is frequently associated with
      intractable focal epilepsy. Epileptogenicity is usually attributed to the
      hemosiderin deposits. Extent of resection is a crucial issue for achieving good
      seizure outcome. AIM: To assess whether seizure outcome is related to the
      extended resection (ER) of surrounding hemosiderin fringe brain tissue. MATERIALS
      AND METHODS: Between April 2000 and April 2008, 132 patients with CCM and
      refractory epilepsy were scheduled for surgery based on the high-resolution
      magnetic resonance imaging (MRI) findings and intensive video
      electroencephalogram (EEG) monitoring. All patients underwent pre- and post
      operative MRI. Based on MRI findings patients were grouped into: ER group (ER,
      hemosiderin completely removed) and lesionectomy group (LE, hemosiderin
      not/partially removed). Post-operative seizure outcome was compared between the
      two groups based on Engel and the International League Against Epilepsy outcome
      scales. RESULTS: At 1-year follow-up of the 86 patients in the ER group, 54
      (74.4%) achieved seizure free outcome and in the LE group of the 46 patients, 20
      (59.5%) achieved seizure-free outcome. At 5-year follow-up, 59.5% (25/42) of
      patients in ER group and 27.8% (5/18) of patients in LE group achieved seizure
      free outcome. ER was not associated with increased neurological morbidity.
      CONCLUSIONS: Our study suggests that complete removal of hemosiderin fringe brain
      tissue surrounding CCMs may improve short-term and long-term seizure outcome.

PMID- 23860151
TI  - The angiotensin converting enzyme insertion/deletion polymorphism and
      intracranial aneurysm: a meta-analysis of case-control studies.
AB  - CONTEXT: Previous studies investigating the association between angiotensin
      converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and intracranial
      aneurysm (IA) have provided inconsistent results and no large systematic review
      or meta-analyses have been conducted regarding this issue. AIM: To confirm
      whether the ACE I/D polymorphism correlates with risk of IA. SETTINGS AND DESIGN:
      We conducted a meta-analysis to increase the statistical power by using all the
      available published data. MATERIALS AND METHODS: Two investigators independently
      searched the PubMed, Medline, Embase, China National Knowledge Infrastructure and
      Chinese Biomedicine Databases for studies published before December 2012. For
      included studies, we performed meta-analyses using the Cochrane RevMan software.
      STATISTICAL ANALYSIS: Summary odds ratios (ORs) and 95% confidence intervals
      (CIs) for ACE I/D polymorphisms and IA were calculated in a fixed-effects model
      or a random-effects model when appropriate. We used Cochran's Q statistic and the
      I 2 statistic to assess heterogeneity and funnel plot to assess potential
      publication bias. We also carried out stratified analyses and sensitivity
      analyses by ethnicity, country and source of control group, sample size and Hardy
      Weinberg equilibrium (HWE) in controls. RESULTS: Six eligible studies were
      reviewed and analyzed, involving 854 cases and 1280 controls. Overall, compared
      with D allele, there was a close relationship between I allele and IA risk (OR:
      1.21, 95% CI: 1.07-1.37, P = 0.003; P(heterogeneity) = 0.56; I2 = 0%). ACE I+
      (I/I and I/D) genotype had significantly increased risk for IA (OR: 1.27, 95% CI:
      1.03-1.57, P = 0.03; P(heterogeneity) = 0.14; I2 = 40%). This association
      remained consistently strong when analyses were limited to studies, in which
      genotype frequencies were in HWE. No publication bias was found in the present
      study. CONCLUSIONS: Our meta-analysis suggests, there is a close relationship
      between ACE I/D polymorphism and IA risk. Since limited studies and subjects were
      included, it is critical that larger and especially well-designed multicentric
      studies, which based on interactions of ACE and different confounding factors
      should be performed to re-evaluate the association.

PMID- 23860152
TI  - Morvan syndrome: after scrotal sac drainage and chemical instillation in
      hydrocele.
AB  - We have described the occurrence of Morvan syndrome (MoS) after scrotal tap and
      injection of sclerosing agent for the treatment of hydrocele in 5 male. The mean
      age was 43.2 years, and the gap between the procedure and development of clinical
      features suggestive of MoS was 1.5-3 months. The neurophysiology studies
      demonstrated hyper excitability of peripheral nerves. In addition, autonomic
      dysfunction, severe insomnia, and neuropsychiatric features were observed.
      Significant VGKC-complex/CASPR-2 antibodies titer were present in all cases.
      Symptoms resolved spontaneously within 6 months of onset. 

PMID- 23860153
TI  - Cervical extradural and extraspinal ependymoma mimicking dumb-bell schwannoma: an
      unusual tumor.
AB  - Ependymomas are common in intramedullary location and extradural location of the
      spinal cord is very rare. A few cases in the lumbosacral region have been
      reported. This report presents a cervical dumb-bell ependymoma with a small
      intraspinal extradural component and a large extraspinal component in the
      posterior triangle of the neck. The tumor was excised in two stages. This is
      probably the first such case report in the cervical region in the world
      literature. Possible histogenesis of ependymoma in this location is also
      discussed. 

PMID- 23860154
TI  - Vagus nerve stimulation for drug-resistant epilepsy in a patient with Mowat
      Wilson syndrome.

PMID- 23860155
TI  - Partial hypopituitarism: a sequel of extrapontine myelinosis.

PMID- 23860156
TI  - Intraventricular hemorrhage in a patient with chronic myeloid leukemia and
      anterior communicating artery aneurysm.

PMID- 23860157
TI  - Hypopitutarism secondary to snake envenomation.

PMID- 23860158
TI  - Transligamentous thenar branch of the median nerve: the million dollar nerve.

PMID- 23860159
TI  - Temporal evolution of hypertrophied vasa vasorum of common carotid artery
      triggered by cerebral ischemia: a serial angiographic investigation.

PMID- 23860160
TI  - Pneumocephalus as uncommon presentation of pneumococcal meningitis.

PMID- 23860161
TI  - Trilobulated fusiform aneurysm from proximal fenestrated segment of dominant A1
      causing subarachnoid hemorrhage.

PMID- 23860162
TI  - Dengue infection presenting as ischemic stroke: an uncommon neurological
      manifestation.

PMID- 23860163
TI  - Y-sign and other diagnostic findings in idiopathic spinal epidural lipomatosis.

PMID- 23860164
TI  - Unusual presentation of hyperphagia after surgery for fourth ventricular
      ependymoma: accessory satiety center or hypothalamic seedlings?

PMID- 23860165
TI  - Brainstem transient ischemic attacks due to compression of pons from a persistent
      primitive trigeminal artery.

PMID- 23860166
TI  - Metachronous occurrence of an intramedullary abscess following radical excision
      of a cervical intramedullary pilocytic astrocytoma.

PMID- 23860167
TI  - Hypoglossal schwannoma presenting as hemi-atrophy of the tongue.

PMID- 23860168
TI  - Glioblastoma multiforme presenting as a fungating mass extending through previous
      craniotomy site.

PMID- 23860169
TI  - Pure sensory deficit at the T3 sensory level as an isolated manifestation of
      lateral medullary infarction.

PMID- 23860170
TI  - Aneurysm of torcula.

PMID- 23860171
TI  - Hemorrhage in meningioma: an unwanted outcome of pregnancy.

PMID- 23860172
TI  - Primary fourth ventricular solitary schwannoma: case report and review of the
      literature.

PMID- 23860173
TI  - Rescuing the falling head.

PMID- 23860174
TI  - A case of primary skull lymphoma: review of literature.

PMID- 23860175
TI  - Carrot stick fracture of cervical spine in ankylosing spondylitis.

PMID- 23860176
TI  - Intra-extradural dumbbell-shaped hemangioblastoma of the cauda equina mimicking
      schwannoma.

PMID- 23860177
TI  - Incidence of malignancies in biopsy-proven inflammatory myopathy: comment and
      erratum.

PMID- 23860178
TI  - Health shocks in the family: gender differences in smoking changes.
AB  - OBJECTIVE: This study estimates the likelihood of starting and stopping smoking
      when respondents and their partners report new chronic illnesses. METHOD:
      Analysis of longitudinal data from the Health and Retirement Study tests whether
      starting or stopping smoking is more likely when (a) the respondent, (b) their
      partner, (c) or both report a new chronic condition, and whether these patterns
      differ by gender. RESULTS: Both men and women are more likely to quit smoking
      when reporting a new chronic condition, relative to when reporting none. However
      only women are more likely to quit smoking when their partners fall ill. Women
      are also more likely than men to start smoking at this time. DISCUSSION: Among
      older couples, women's smoking changes are more sensitive to health shocks in the
      partnership. Interventions aimed at preventing unhealthy behaviors should pay
      attention to how each partner deals with the stress of health shocks.

PMID- 23860179
TI  - Factors related to positive mental health in a stigmatized minority: an
      investigation of older gay men.
AB  - OBJECTIVES: This study investigates factors related to the positive mental health
      of older Australian gay men, who are challenged by both age- and sexuality
      related stigma. METHODS: A national online survey was conducted among 422 gay
      identified men aged 40 years and older. Positive mental health was measured using
      the Short Warwick-Edinburgh Mental Well-being Scale (SWEMWBS). RESULTS:
      Regression analyses revealed men were psychologically healthier if they were
      employed full-time, had a higher income, were in a relationship, received greater
      social support, had many close friends, felt connected to the gay community,
      believed the public felt positively toward their group, and had not experienced
      discrimination in the past year. A multivariate linear regression found social
      support to be the most important of all these factors, with support from friends
      particularly critical. DISCUSSION: These findings provide new guidance to health
      agencies that seek to improve the mental health and well-being of older gay men.

PMID- 23860180
TI  - Platelet-derived growth factor receptor beta serum concentrations during first
      line therapy in ovarian cancer.
AB  - OBJECTIVES: Angiogenesis plays an important role in ovarian cancer. The
      interaction of platelet-derived growth factor receptor-beta (PDGFR-beta) with
      vascular endothelial growth factor (VEGF) in the process of angiogenesis may
      represent an essential feature in the progression of the disease. METHODS:
      Patients with epithelial ovarian cancer, who underwent primary surgery and
      platinum-based first-line chemotherapy, were included. A total of 133 serum
      samples from 39 patients were analyzed. Samples were prospectively collected at 4
      time points: (1) before surgery, (2) after surgery and before chemotherapy, (3)
      during chemotherapy and (4) after chemotherapy. Serum PDGFR-beta was quantified
      by ELISA. We analyzed the correlation of serum levels to chemotherapy response,
      progression-free and overall survival (PFS and OS) and the serum markers CA-125
      and VEGF-165. RESULTS: Serum concentration of PDGFR-beta ranged between 4 and 72
      ng/ml and increased significantly during first-line chemotherapy (p = 0.019).
      PDGFR-beta serum concentrations showed an inverse correlation with CA-125 and
      VEGF-165 after chemotherapy (r = -0.495, p = 0.003 and r = -0.345, p = 0.04,
      respectively). Increased PDGFR-beta serum levels after chemotherapy were
      significantly correlated with better PFS (p = 0.026) and OS (p = 0.013) in a
      univariate analysis. CONCLUSION: PDGFR-beta might be a useful biomarker in terms
      of prognosis and could be important as antiangiogenic agents become a component
      of standard treatment in ovarian cancer.

PMID- 23860181
TI  - Ovicidal activity of three insect growth regulators against Aedes and Culex
      mosquitoes.
AB  - Interspecific variations in the susceptibility of freshly and embryonated eggs of
      Aedes albopictus, Ae. aegypti, Ae. atropalpus and Culex pipiens were tested
      against three classes of insect growth regulators (IGRs) including ecdysone
      agonist (azadirachtin), chitin synthesis inhibitor (diflubenzuron) and juvenile
      hormone analog (pyriproxyfen) at 0.001, 0.01, 0.1 and 1.0ppm concentrations. Egg
      hatching inhibition was dose dependent, the highest being at 1.0ppm concentration
      for freshly laid eggs of Ae. albopictus (pyriproxyfen: 80.6%, azadirachtin: 42.9%
      and diflubenzuron: 35.8%). Aedes aegypti showed lower egg hatching inhibition
      when exposed to pyriproxyfen (47.3%), azadirachtin (15.7%) and diflubenzuron
      (25.5%). Freshly laid eggs of Cx. pipiens were most susceptible to diflubenzuron.
      Aedes atropalpus eggs were tolerant to all three classes of IGRs. Embryonated
      eggs of Ae. albopictus, Ae. aegypti, Ae. atropalpus and Cx. pipiens were
      resistant to pyriproxyfen, azadirachtin and diflubenzuron than freshly laid eggs.
      The median desiccation time (DT50) of Ae. atropalpus eggs was maximum (5.1h) as
      compared to Ae. aegypti (4.9h), Ae. albopictus (3.9h) or Cx. pipiens (1.7h) eggs.
      Insignificant relationship between the rates of desiccation and egg hatching
      inhibition suggests other factors than physical providing eggs the ability to
      tolerate exposures to various IGRs. Egg hatching inhibition was due to the
      alteration in embryonic development caused by IGRs. Changes in the egg shell
      morphology and abnormal egg hatching from the side of the egg wall instead of
      operculum, was observed at higher concentrations of diflubenzuron. Morphological
      and physiological variations in eggs may be the key factor to influence the
      ovicidal efficacy of IGRs. The present data provide a base line for the
      improvement of the ovicidal efficacy of the insecticide and its formulation. 

PMID- 23860182
TI  - Development of a cell line from Echinococcus granulosus germinal layer.
AB  - In vitro culture of parasitic helminths provides an important tool to study cell
      regeneration and physiology, as well as for molecular biology and genetic
      engineering studies. In the present study, we established in vitro propagation of
      cells from Echinococcus granulosus germinal cyst layer. E. granulosus germinal
      cells grew beyond 100 passages and showed no signs of reduced proliferation
      capacity. Microscopic analysis revealed that cells grew both attached to the
      substrate and in suspension, forming three-dimensional structures like mammalian
      stem cell aggregates. Examination of the chromosome number of attached germinal
      cells showed a high degree of heteroploidy, suggesting the occurrence of
      transformation during culture. Monolayer cells survived cryopreservation and were
      able to proliferate after thawing. Based on the characteristics displayed by E.
      granulosus germinal cells, we establish a cell line from the E. granulosus
      germinal layer. Furthermore, we propose that this cell line could be useful for
      drug screening and for obtaining parasite material. 

PMID- 23860183
TI  - Assessing the impact of a school intervention to promote students' knowledge and
      practices on correct antibiotic use.
AB  - The clinical efficacy of antibiotics depends on their correct use. Widespread
      ignorance and inappropriate attitudes to antibiotic use have been identified
      among consumers. In order to improve the knowledge of middle-school students on
      antibiotics and their correct use, 82 ninth-grade students were enrolled in a
      teaching activity. The teaching activity consisted of a slide show presentation
      followed by discussion in a regular class. To evaluate the impact of the teaching
      activity the students were asked to answer a questionnaire before and after the
      activity. This study aimed: (1) to evaluate knowledge on the use of antibiotics
      in students of two schools in the north of Portugal and (2) to evaluate the
      efficacy of the school intervention in improving students' knowledge on correct
      antibiotic use. We found lack of knowledge among students regarding antibiotic
      spectra and indications and incorrect attitudes in the pre-test. Significant
      increases in knowledge were observed after implementation of the teaching
      activity. Knowledge of the correct use of antibiotics for bacterial diseases
      rather than viral diseases rose from 43% to 76% in the post-test (p < 0.01).
      Knowledge of the risk of bacterial resistance to antibiotics from their incorrect
      use rose from 48% to 74% in the post-test (p < 0.05). We believe that it is
      important to reinforce the teaching activities on microbiology and antibiotic use
      at the middle school level. 

PMID- 23860184
TI  - Retroperitoneal hemorrhage after cardiac catheterization and percutaneous
      coronary interventions.

PMID- 23860185
TI  - Agreement between self-reports and medical records of cardiovascular disease in
      octogenarians.
AB  - OBJECTIVE: Self-reported health and disease status is a common method used in
      epidemiologic studies and surveys involving younger populations, but its
      reliability in octogenarians is unknown. The objective of the present study was
      to examine the level of agreement between self-reports and medical records on
      specific cardiovascular diagnoses. STUDY DESIGN AND SETTING: The Life and Living
      to Advanced Age: a Cohort Study in New Zealand recruited 937 octogenarians in New
      Zealand. Standardized questionnaires were administered to determine
      sociodemographic status and medical history. Diagnoses of myocardial infarction
      (MI), stroke, congestive heart failure (CHF), and hypertension were compared
      between self-reports and two combined sources of medical records. RESULTS: There
      were moderate levels of agreement between self-reports and medical records for
      MI, stroke, and hypertension (kappa = 0.43-0.45) and low levels for CHF (kappa =
      0.19). The proportion of discordance for MI, stroke, CHF, and hypertension was
      16%, 12%, 22%, and 27%, respectively. Adjusting for socioeconomic-demographic
      status and cognitive function, the number of comorbidities is highly associated
      with agreement between self-reports and medical records (P < 0.01). Gender,
      socioeconomic status, and cognitive function were also related to agreement
      between self-reports and medical records, but the strength of association was
      ethnic specific. CONCLUSION: Self-reported information on specific cardiovascular
      conditions has only modest reliability in octogenarians and is associated with
      number of comorbidities.

PMID- 23860186
TI  - The nanoparticulation by octaarginine-modified liposome improves alpha
      galactosylceramide-mediated antitumor therapy via systemic administration.
AB  - Alpha-galactosylceramide (alphaGC), a lipid antigen present on CD1d molecules, is
      predicted to have clinical applications as a new class of adjuvant, because
      alphaGC strongly activates natural killer T (NKT) cells which produce large
      amounts of IFN-gamma. Here, we incorporated alphaGC into stearylated octaarginine
      modified liposomes (R8-Lip), our original delivery system developed for vaccines,
      and investigated the effect of nanoparticulation. Unexpectedly, the systemic
      administered R8-Lip incorporating alphaGC (alphaGC/R8-Lip) failed to improve the
      immune responses mediated by alphaGC compared with soluble alphaGC in vivo,
      although alphaGC/R8-Lip drastically enhanced alphaGC presentation on CD1d in
      antigen presenting cells in vitro. Thus, we optimized the alphaGC/R8-Lip in vivo
      to overcome this inverse correlation. In optimization in vivo, we found that size
      control of liposome and R8-modification were critical for enhancing the
      production of IFN-gamma. The optimization led to the accumulation of alphaGC/R8
      Lip in the spleen and a positive therapeutic effect against highly malignant B16
      melanoma cells. The optimized alphaGC/R8-Lip also enhanced alphaGC presentation
      on CD1d in antigen presenting cells and resulted in an expansion in the
      population of NKT cells. Herein, we show that R8-Lip is a potent delivery system,
      and size control and R8-modification in liposomal construction are promising
      techniques for achieving systemic alphaGC therapy. 

PMID- 23860187
TI  - Tumor-targeting nanogel that can function independently for both photodynamic and
      photothermal therapy and its synergy from the procedure of PDT followed by PTT.
AB  - A dual-function nano-system for synergistic photodynamic therapy (PDT) and
      photothermal therapy (PTT) was constructed. Gold nanorods (GNRs) as a PTT agent
      and chlorin e6 (Ce6) as a photosensitizer (PS) for PDT were loaded into a
      chitosan-functionalized, Pluronic-based nanogel that was proven to be an
      efficient delivery vehicle to the tumor site in vivo. Previously reported
      combined therapy systems relied on quenching and de-quenching of PS for PDT upon
      thermo-impact of PTT, thus only PTT followed by PDT procedure was possible. In
      contrast, the present dual-acting system has no quenching between PS and GNRs by
      preventing direct contact and self-aggregation of photo-sensitizers, allowing
      independent PDT or PTT procedure. In both in vitro cell culture and in vivo tumor
      bearing mice experiments, a remarkably enhanced tumor ablation compared to the
      treatment of PDT or PTT only was observed by the treatment of PDT followed by
      PTT, but not significantly by the treatment of PTT followed by PDT. Thus, the
      present study demonstrated the synergistic effect of PDT and PTT in a sequence
      dependent manner, and our system is a promising dual function nano system to
      achieve the enhanced phototherapy in vivo. 

PMID- 23860188
TI  - CCR5 and FPR1 mediate neutrophil recruitment in endotoxin-induced lung injury.
AB  - Recruitment of neutrophils, regarded as a key mechanism in acute lung injury
      (ALI), is orchestrated by cell adhesion molecules and chemokines. While the
      importance of cell adhesion molecules has been carefully investigated, little is
      known about the importance of chemokines and their receptors in the recruitment
      of neutrophils in models of ALI. Wild-type Ccr2(-/-), Ccr5(-/-), Fpr1(-/-) or
      Fpr2(-/-) mice were exposed to aerosolized lipopolysaccharide and the number of
      neutrophils in the lung tissue (intravascular, interstitial) and in the
      bronchoalveolar lavage was quantified. Lack of CCR5 or FPR1, but not CCR2 or
      FPR2, significantly reduced lung neutrophil infiltration in all compartments.
      Similarly, blockade of CCR5 or FPR1 with specific antagonists reduced counts of
      alveolar, interstitial and intravascular neutrophils. Such treatments also
      inhibited lung edema formation and histological lung tissue alterations, thus
      underscoring the protective role of CCR5 and FPR1 neutralizing strategies in ALI.

PMID- 23860189
TI  - The role of miRNA in inflammation and autoimmunity.
AB  - miRNAs are small non-coding RNA molecules that modulate the expression of
      multiple protein-encoding genes at the post-transcriptional level. They have
      recently been recognized as powerful regulators of numerous genes and pathways in
      the pathogenesis of inflammatory and autoimmune diseases. The targets of most
      miRNAs remain unknown and their roles in biological processes such as cell
      differentiation, proliferation, and death (apoptosis) are not clearly understood.
      In this review we will discuss how certain candidate miRNAs affect inflammatory
      and immune mediated diseases by regulating their cellular and molecular targets.
      We focused the influence of gender and sex hormones on miRNA. We believe that
      understanding the role of miRNAs could shed light on the cause and progression of
      many inflammatory and autoimmune diseases and eventually lay the groundwork for
      therapeutic options. 

PMID- 23860190
TI  - Diagnostic usefulness of MUC1 and MUC4 for distinguishing between metastatic
      adenocarcinoma cells and reactive mesothelial cells in effusion cell blocks.
AB  - OBJECTIVE: The aim of our study was to determine the diagnostic value of MUC1 and
      MUC4 for distinguishing between metastatic adenocarcinoma cells (MAC) and
      reactive mesothelial cells (RMC) in effusion fluids. STUDY DESIGN: A total of 237
      cell block specimens from pleural and peritoneal effusions, including 196
      malignant effusions with MAC and 41 benign effusions with RMC, were stained with
      antibodies against MUC1 and MUC4. Membranous staining with or without cytoplasmic
      staining was considered to be positive. RESULTS: MUC1 immunoreactivity was
      observed in 194 (99.0%) of 196 cases of MAC and in 20 (48.8%) of 41 cases of RMC.
      MUC4 immunoreactivity was observed in 174 (88.8%) of 196 cases of MAC and in 4
      (9.8%) of 41 cases of RMC. For distinguishing MAC from RMC, the MUC1 reactivity
      was found to be 99.0% sensitive and 51.2% specific with a positive predictive
      value of 90.7% and a negative predictive value of 91.3%. The sensitivity of MUC4
      for MAC was 88.8%, the specificity was 90.2%, the negative predictive value was
      62.7%, and the positive predictive value was 97.8%. CONCLUSION: Our data suggest
      that MUC4 appears to be a sensitive and specific marker for differentiating
      between MAC and RMC.

PMID- 23860191
TI  - Plasmapheresis as an alternative to high-dose intravenous immunoglobulin in the
      prevention of gestational alloimmune liver disease.
AB  - Gestational alloimmune liver disease occurs due to trans-placental passage of
      maternal antibodies to a fetal hepatocyte antigen that produces complement
      mediated hepatocyte injury. High-dose intravenous immunoglobulin therapy during
      gestation is highly effective at decreasing the risk to the neonate but treatment
      is expensive. This case presents for the first time the use of plasmapheresis as
      a potential cheaper alternative when treatment with immunoglobulins is
      unavailable. 

PMID- 23860192
TI  - The effect of involuntary motor activity on myoelectric pattern recognition: a
      case study with chronic stroke patients.
AB  - OBJECTIVE: This study investigates the effect of the involuntary motor activity
      of paretic-spastic muscles on the classification of surface electromyography
      (EMG) signals. APPROACH: Two data collection sessions were designed for 8 stroke
      subjects to voluntarily perform 11 functional movements using their affected
      forearm and hand at relatively slow and fast speeds. For each stroke subject, the
      degree of involuntary motor activity present in the voluntary surface EMG
      recordings was qualitatively described from such slow and fast experimental
      protocols. Myoelectric pattern recognition analysis was performed using different
      combinations of voluntary surface EMG data recorded from the slow and fast
      sessions. MAIN RESULTS: Across all tested stroke subjects, our results revealed
      that when involuntary surface EMG is absent or present in both the training and
      testing datasets, high accuracies (>96%, >98%, respectively, averaged over all
      the subjects) can be achieved in the classification of different movements using
      surface EMG signals from paretic muscles. When involuntary surface EMG was solely
      involved in either the training or testing datasets, the classification
      accuracies were dramatically reduced (<89%, <85%, respectively). However, if both
      the training and testing datasets contained EMG signals with the presence and
      absence of involuntary EMG interference, high accuracies were still achieved
      (>97%). SIGNIFICANCE: The findings of this study can be used to guide the
      appropriate design and implementation of myoelectric pattern recognition based
      systems or devices toward promoting robot-aided therapy for stroke
      rehabilitation.

PMID- 23860193
TI  - A new, evidence-based estimate of patient harms associated with hospital care.
AB  - OBJECTIVES: Based on 1984 data developed from reviews of medical records of
      patients treated in New York hospitals, the Institute of Medicine estimated that
      up to 98,000 Americans die each year from medical errors. The basis of this
      estimate is nearly 3 decades old; herein, an updated estimate is developed from
      modern studies published from 2008 to 2011. METHODS: A literature review
      identified 4 limited studies that used primarily the Global Trigger Tool to flag
      specific evidence in medical records, such as medication stop orders or abnormal
      laboratory results, which point to an adverse event that may have harmed a
      patient. Ultimately, a physician must concur on the findings of an adverse event
      and then classify the severity of patient harm. RESULTS: Using a weighted average
      of the 4 studies, a lower limit of 210,000 deaths per year was associated with
      preventable harm in hospitals. Given limitations in the search capability of the
      Global Trigger Tool and the incompleteness of medical records on which the Tool
      depends, the true number of premature deaths associated with preventable harm to
      patients was estimated at more than 400,000 per year. Serious harm seems to be 10
      to 20-fold more common than lethal harm. CONCLUSIONS: The epidemic of patient
      harm in hospitals must be taken more seriously if it is to be curtailed. Fully
      engaging patients and their advocates during hospital care, systematically
      seeking the patients' voice in identifying harms, transparent accountability for
      harm, and intentional correction of root causes of harm will be necessary to
      accomplish this goal.

PMID- 23860194
TI  - Use of failure modes, effects, and criticality analysis to compare the
      vulnerabilities of laparoscopic versus open appendectomy.
AB  - PURPOSE: To measure the feasibility of using FMECA applied to the surgery and
      then compare the vulnerabilities of laparoscopic versus open appendectomy by
      using FMECA. METHODS: The FMECA study was performed on each single selected phase
      of appendectomy and on complication-related data during the period January 1,
      2009, to December 31, 2010. The risk analysis phase was completed by evaluation
      of the criticality index (CI) of each appendectomy-related failure mode (FM). The
      CI is calculated by multiplying the estimated frequency of occurrence (O) of the
      FM, by the expected severity of the injury to the patient (S), and the
      detectability (D) of the FM. RESULTS: In the first year of analysis (2009), 177
      appendectomies were performed, 110 open and 67 laparoscopic. Eleven adverse
      events were related to the open appendectomy: 1 bleeding (CI: 8) and 10
      postoperative infections (CI: 32). Three adverse events related to the
      laparoscopic approach were recorded: 1 postoperative infection (CI: 8) and 2
      incorrect extractions of the appendix through the umbilical port (CI: 6). In the
      second year of analysis (2010), 158 appendectomies were performed, 69 open and 89
      laparoscopic. Four adverse events were related to the open appendectomy: 1
      incorrect management of the histological specimen (CI: 2), 1 dehiscence of the
      surgical wound (CI: 6), and 2 infections (CI: 6). No adverse events were recorded
      in laparoscopic approach. CONCLUSION: FMECA helped the staff compare the 2
      approaches through an accurate step-by-step analysis, highlighting that
      laparoscopic appendectomy is feasible and safe, associated with a lower incidence
      of infection and other complications, reduced length of hospital stay, and an
      apparent lower procedure-related risk.

PMID- 23860195
TI  - The relationship between nurse staffing and failure to rescue: where does it
      matter most?
AB  - OBJECTIVES: This study further expands on the relationship between nurse staffing
      levels and patient outcomes, in particular, failure to rescue. Many studies are
      based on single-site hospitals or single-year data, thus limiting the
      generalizations of the findings. The purpose was to evaluate in a multisite
      multiyear study the relationship between unit-level nurse staffing and FTR
      mortality, for ICU and non-ICU patients. METHODS: Using administrative and actual
      unit level nurse staffing data, we used AHRQ 2003 Patient Safety Indicator (2003)
      software and matched those with the patient's discharge month. Fixed effects
      multilevel logistic analyses were used to take into account the hierarchical
      structure of the database and patient clustering within units. We controlled for
      patient demographics, clinical conditions, and CCS categories. RESULTS: The
      majority (94%) of cases were discharged from general care units, ICUs reported
      higher nurse staffing levels based on patient complexity. Expired cases were 3
      years older, male, and nonwhite. For general care discharges, the relationship
      between RN level HPPD approached significance (P = 0.07), suggesting increased
      odds of higher FTR mortality with higher staffing levels. CONCLUSIONS: We did not
      observe any of the expected associations between the nurse staffing variables and
      FTR for either general care unit or ICU discharges. The comprehensive risk
      adjustments provided adequate "leveling of the playing field" to evaluate the
      impact of unit-based nurse staffing levels on FTR mortality. Future studies
      should evaluate the influence of unit environment and patient risk.

PMID- 23860196
TI  - Avoidable iatrogenic hypoglycemia in patients on peritoneal dialysis: the risks
      of nonspecific glucose monitoring devices and drug-device interaction.
AB  - BACKGROUND AND OBJECTIVES: Health care professionals (HCPs) depend upon "point-of
      care" (POC) glucometers to provide appropriate treatment in emergency and
      hospital environments. Most devices located in these settings use nonspecific
      test strip methodology (NSTSM), which is unable to distinguish glucose from
      nonglucose sugars, including maltose. This flaw can result in erroneous
      administration of insulin and harm to patients. Icodextrin is a colloidal osmotic
      agent used in peritoneal dialysis (PD) solutions to augment ultrafiltration and
      waste removal. The main metabolite of icodextrin is maltose. DESIGN, SETTING,
      PARTICIPANTS, AND MEASUREMENTS: Three representative case reports of
      inappropriate medical action related to in-hospital use of NSTSM monitoring in PD
      patients using icodextrin are provided to emphasize importance of this
      interaction and HCP awareness. RESULTS: PD patients using icodextrin before
      hospitalization exhibited marked discrepancy between blood glucose (BG)
      measurements obtained from POC-NSTSM glucometers and those obtained by glucose
      specific methods in clinical chemistry laboratories leading to inappropriate
      administration of insulin by HCPs and symptomatic hypoglycemia in all patients.
      None of the patients received icodextrin during hospitalization. CONCLUSIONS: Non
      nephrology HCPs are unaware that POC glucometers are nonglucose specific and do
      not possess comprehensive knowledge of drug metabolism, particularly for
      uncommonly seen agents. The case reports highlight the absolute need for use of
      glucose-specific assays in BG determinations for patients using icodextrin within
      2 weeks of hospitalization. To avoid future devastating consequences including
      severe hypoglycemia, coma, or death related to the drug-device interaction
      described, hospital protocols should require that all PD patients' BGs are
      measured in central chemistry laboratories.

PMID- 23860197
TI  - Rapid diagnosis and staging of colorectal cancer via high-resolution magic angle
      spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy of intact tissue
      biopsies.
AB  - OBJECTIVE: To develop novel metabolite-based models for diagnosis and staging in
      colorectal cancer (CRC) using high-resolution magic angle spinning nuclear
      magnetic resonance (HR-MAS NMR) spectroscopy. BACKGROUND: Previous studies have
      demonstrated that cancer cells harbor unique metabolic characteristics relative
      to healthy counterparts. This study sought to characterize metabolic properties
      in CRC using HR-MAS NMR spectroscopy. METHODS: Between November 2010 and January
      2012, 44 consecutive patients with confirmed CRC were recruited to a prospective
      observational study. Fresh tissue samples were obtained from center of tumor and
      5 cm from tumor margin from surgical resection specimens. Samples were run in
      duplicate where tissue volume permitted to compensate for anticipated sample
      heterogeneity. Samples were subjected to HR-MAS NMR spectroscopic profiling and
      acquired spectral data were imported into SIMCA and MATLAB statistical software
      packages for unsupervised and supervised multivariate analysis. RESULTS: A total
      of 171 spectra were acquired (center of tumor, n = 88; 5 cm from tumor margin, n
      = 83). Cancer tissue contained significantly increased levels of lactate (P <
      0.005), taurine (P < 0.005), and isoglutamine (P < 0.005) and decreased levels of
      lipids/triglycerides (P < 0.005) relative to healthy mucosa (R2Y = 0.94; Q2Y =
      0.72; area under the curve, 0.98). Colon cancer samples (n = 49) contained higher
      levels of acetate (P < 0.005) and arginine (P < 0.005) and lower levels of
      lactate (P < 0.005) relative to rectal cancer samples (n = 39). In addition
      unique metabolic profiles were observed for tumors of differing T-stage.
      CONCLUSIONS: HR-MAS NMR profiling demonstrates cancer-specific metabolic
      signatures in CRC and reveals metabolic differences between colonic and rectal
      cancers. In addition, this approach reveals that tumor metabolism undergoes
      modification during local tumor advancement, offering potential in future staging
      and therapeutic approaches.

PMID- 23860198
TI  - The balance of risk score for allocation in liver transplantation.

PMID- 23860199
TI  - Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary
      gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial.
AB  - OBJECTIVE: To conduct the first adjuvant trial of imatinib mesylate for treatment
      of gastrointestinal stromal tumor (GIST). BACKGROUND: GIST is the most common
      sarcoma. Although surgical resection has been the mainstay of therapy for
      localized, primary GIST, postoperative tumor recurrence is common. The KIT
      protooncogene or, less frequently, platelet-derived growth factor receptor alpha
      is mutated in GIST; the gene products of both are inhibited by imatinib mesylate.
      METHODS: This was a phase II, intergroup trial led by the American College of
      Surgeons Oncology Group, registered at ClinicalTrials.gov as NCT00025246. From
      September 2001 to September 2003, we accrued 106 patients who had undergone
      complete gross tumor removal but were deemed at high risk for recurrence.
      Patients were prescribed imatinib 400 mg per day for 1 year and followed with
      serial radiologic evaluation. The primary endpoint was overall survival (OS).
      RESULTS: After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rates
      were 99%, 97%, and 83%, which compared favorably with a historical 5-year OS rate
      of 35%. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 96%,
      60%, and 40%. On univariable analysis, age and mitotic rate were associated with
      OS. On multivariable analysis, the RFS rate was lower with increasing tumor size,
      small bowel site, KIT exon 9 mutation, high mitotic rate, and older age.
      CONCLUSIONS: Adjuvant imatinib in patients with primary GIST who are at high risk
      of recurrence prolongs OS compared with that of historical controls. Optimal
      duration of adjuvant therapy remains undefined. (NCT00025246).

PMID- 23860200
TI  - Defining "the elderly" undergoing major gastrointestinal resections: receiver
      operating characteristic analysis of a large ACS-NSQIP cohort.
AB  - OBJECTIVE: "The elderly" is an often used but poorly defined descriptor of
      surgical patients. Investigators have used varying subjectively determined age
      cutoffs to report outcomes in the elderly. We set out to use objective outcomes
      data to determine the "at-risk" elderly population. METHODS:  PATIENTS: 129,331
      patients identified from the ACS-NSQIP database (2005-2010) undergoing major
      gastrointestinal resections. OUTCOME: Mortality. STATISTICAL METHODS: Locally
      weighted regression was used to fit the trend line of mortality over age.
      Receiver operating characteristic analysis was used to identify the "predictive
      age" for mortality. RESULTS: Mortality steadily increases with age. On receiver
      operating characteristic analysis, there is a nonlinear transition zone (50-75
      years of age) flanked by 2 linear zones on either end. The younger linear zone
      showed a low mortality increase (0.5% per decade). Larger mortality increase with
      age (5.3% per decade) was observed at the older age end. Similar patterns were
      observed for large-volume surgical subtypes, with clustering of a "critical age"
      beyond which mortality increases dramatically at 75 +/- 2 years. Receiver
      operating characteristic analysis identified the "optimum age" for mortality
      being 68.5 years (area under the curve = 0.72, sensitivity = 66.6%, and
      specificity = 65.5%). CONCLUSIONS: Mortality risk for major gastrointestinal
      surgical resections starts increasing at 50 years of age, and at 75 years of age,
      it starts increasing very rapidly. The optimum age of 68.5 years predicts
      mortality with the best combination of sensitivity and specificity. These ages
      should be used to standardize outcome data and focus perioperative resources to
      improve outcomes.

PMID- 23860201
TI  - The challenges for cardiac vascular precursor cell therapy: lessons from a very
      elusive precursor.
AB  - There is compelling evidence that cardiovascular disorders arise and/or progress
      due mainly to endothelial dysfunction. Novel therapeutic strategies aim to
      generate new myocardial tissue using cells with regenerative potential, either
      alone or in combination with biomaterials, cytokines and advanced monitoring
      devices. Among the human adult progenitor cells used in such methods, those
      historically termed 'endothelial progenitor cells' show promise for vascular
      growth and repair. Asahara et al. [Science 1997;275:964-967] initially described
      putative endothelial cell precursors in 1997. Subsequently, distinct cell
      populations termed endothelial colony-forming units-Hill, circulating angiogenic
      cells and endothelial colony-forming cells were identified that varied in terms
      of phenotype, vascular homeostasis contribution and purity. Notably, most of
      these cells are not genuine vascular precursor cells belonging to the endothelial
      lineage. This review provides a broad overview of the main properties of the
      endothelium, focusing on the basis governing its growth and repair. We discuss
      efforts to identify true vascular precursors, a matter of debate for the past 15
      years, as well as recent methodological advances in identifying new hierarchies
      of more homogeneous, clonogenic and proliferative vascular endothelial-lineage
      precursors. Consideration of these issues provides insights that may help develop
      more effective therapies against human diseases that involve vascular deficits. 

PMID- 23860202
TI  - Erythropoiesis stimulating agents: a personal journey.

PMID- 23860203
TI  - Epoetin alfa: to give or not to give.

PMID- 23860204
TI  - Adding epoetin alfa to intense dose-dense adjuvant chemotherapy for breast
      cancer: randomized clinical trial.
AB  - BACKGROUND: The AGO-ETC trial compared 5-year relapse-free survival of intense
      dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and
      cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled
      epirubicin/cyclophosphamide followed by paclitaxel (EC->T) (every 3 weeks) as
      adjuvant treatment in high-risk breast cancer patients. The objective of this
      study was to evaluate the safety and efficacy of epoetin alfa in a second
      randomization of the intense dose-dense arm. METHODS: One thousand two hundred
      eighty-four patients were enrolled; 658 patients were randomly assigned to the
      IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further
      randomly assigned to the epoetin alfa group, and 319 were randomly assigned to
      the non-erythropoiesis-stimulating agent (ESA) control group. Primary efficacy
      endpoints included change in hemoglobin level from baseline to Cycle 9 and the
      percentage of subjects requiring red blood cell transfusion. Relapse-free
      survival, overall survival, and intramammary relapse were secondary endpoints
      estimated with Kaplan-Meier and Cox regression methods. Except for the primary
      hypothesis, all statistical tests were two-sided. RESULTS: Epoetin alfa avoided
      the decrease in hemoglobin level (no decrease in the epoetin alfa group vs 
      2.20g/dL change for the control group; P < .001) and statistically significantly
      reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs
      28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa
      arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa
      treatment did not affect overall survival, relapse-free survival, or intramammary
      relapse. CONCLUSIONS: Epoetin alfa resulted in improved hemoglobin levels and
      decreased transfusions without an impact on relapse-free or overall survival.
      However, epoetin alfa had an adverse effect, resulting in increased thrombosis.

PMID- 23860205
TI  - Association between phosphorylated AMP-activated protein kinase and MAPK3/1
      expression and prognosis for patients with gastric cancer.
AB  - OBJECTIVES: Phosphorylated AMP-activated protein kinase (pAMPK) plays a central
      role in cellular metabolic sensing and energy balance homeostasis, and interacts
      with various pathways [e.g., TP53, mTOR, NUAK2 (sucrose nonfermenting-like
      kinase), MAPK3/1 (ERK) and PDK]. Therefore, the present study analyzed the
      expression of pAMPK, NUAK2, MAPK3/1 and PDK-1 and their effect on the survival of
      patients with resected gastric cancer. METHODS: A total of 621 patients with
      gastric adenocarcinoma surgically resected with curative intent were enrolled in
      the study. Immunohistochemical staining for pAMPK, NUAK2, MAPK3/1 and PDK-1 was
      performed using tissue microarrays of surgical specimens of gastric cancer
      tissue. RESULTS: Positive pAMPK, NUAK2, MAPK3/1 and PDK-1 expression was observed
      in 379 (61.0%), 257 (41.4%), 327 (52.7%) and 67 (10.8%) cases, respectively.
      Multivariate survival analysis showed a significantly better survival for the
      patients with positive pAMPK or MAPK3/1 expression than for the patients with a
      negative expression [pAMPK: disease-free survival (DFS), hazard ratio (HR) =
      0.750, 95% confidence interval (CI) = 0.568-0.970, p = 0.030; MAPK3/1: DFS, HR =
      0.692, 95% CI = 0.720-0.974, p = 0.021), while NUAK2 or PDK-1 expression had no
      effect on survival. CONCLUSION: pAMPK or MAPK3/1 expression was found to be an
      independent prognostic marker for patients with resected gastric cancer.

PMID- 23860206
TI  - Enhanced development of azoxymethane-induced colonic preneoplastic lesions in
      hypertensive rats.
AB  - Metabolic syndrome is associated with an increased risk of colorectal cancer.
      This study investigated the impact of hypertension, a component of metabolic
      syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm
      (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF)
      diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non
      diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly
      intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the
      last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared
      to the control WKY rats. Serum levels of angiotensin-II, the active product of
      the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but
      only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and
      hyperleptinemia and exhibited an increase in adipose tissue. The development of
      AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was
      significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared
      to WKY normotensive rats. Furthermore, induction of oxidative stress and
      exacerbation of inflammation were observed in the colonic mucosa and systemically
      in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role
      in the early stage of colorectal carcinogenesis by inducing oxidative stress and
      chronic inflammation, which might be associated with activation of the renin
      angiotensin system. 

PMID- 23860207
TI  - The role of microRNAs in breast cancer stem cells.
AB  - The concept of the existence of a subset of cancer cells with stem cell-like
      properties, which are thought to play a significant role in tumor formation,
      metastasis, resistance to anticancer therapies and cancer recurrence, has gained
      tremendous attraction within the last decade. These cancer stem cells (CSCs) are
      relatively rare and have been described by different molecular markers and
      cellular features in different types of cancers. Ten years ago, a novel class of
      molecules, small non-protein-coding RNAs, was found to be involved in
      carcinogenesis. These small RNAs, which are called microRNAs (miRNAs), act as
      endogenous suppressors of gene expression that exert their effect by binding to
      the 3'-untranslated region (UTR) of large target messenger RNAs (mRNAs).
      MicroRNAs trigger either translational repression or mRNA cleavage of target
      mRNAs. Some studies have shown that putative breast cancer stem cells (BCSCs)
      exhibit a distinct miRNA expression profile compared to non-tumorigenic breast
      cancer cells. The deregulated miRNAs may contribute to carcinogenesis and self
      renewal of BCSCs via several different pathways and can act either as oncomirs or
      as tumor suppressive miRNAs. It has also been demonstrated that certain miRNAs
      play an essential role in regulating the stem cell-like phenotype of BCSCs. Some
      miRNAs control clonal expansion or maintain the self-renewal and anti-apoptotic
      features of BCSCs. Others are targeting the specific mRNA of their target genes
      and thereby contribute to the formation and self-renewal process of BCSCs.
      Several miRNAs are involved in epithelial to mesenchymal transition, which is
      often implicated in the process of formation of CSCs. Other miRNAs were shown to
      be involved in the increased chemotherapeutic resistance of BCSCs. This review
      highlights the recent findings and crucial role of miRNAs in the maintenance,
      growth and behavior of BCSCs, thus indicating the potential for novel diagnostic,
      prognostic and therapeutic miRNA-based strategies. 

PMID- 23860208
TI  - Effect of amphipathic HIV fusion inhibitor peptides on POPC and POPC/cholesterol
      membrane properties: a molecular simulation study.
AB  - T-20 and T-1249 fusion inhibitor peptides were shown to interact with 1-palmitoyl
      2-oleyl-phosphatidylcholine (POPC) (liquid disordered, ld) and POPC/cholesterol
      (1:1) (POPC/Chol) (liquid ordered, lo) bilayers, and they do so to different
      extents. Although they both possess a tryptophan-rich domain (TRD), T-20 lacks a
      pocket binding domain (PBD), which is present in T-1249. It has been postulated
      that the PBD domain enhances FI interaction with HIV gp41 protein and with model
      membranes. Interaction of these fusion inhibitor peptides with both the cell
      membrane and the viral envelope membrane is important for function, i.e.,
      inhibition of the fusion process. We address this problem with a molecular
      dynamics approach focusing on lipid properties, trying to ascertain the
      consequences and the differences in the interaction of T-20 and T-1249 with ld
      and lo model membranes. T-20 and T-1249 interactions with model membranes are
      shown to have measurable and different effects on bilayer structural and
      dynamical parameters. T-1249's adsorption to the membrane surface has generally a
      stronger influence in the measured parameters. The presence of both binding
      domains in T-1249 appears to be paramount to its stronger interaction, and is
      shown to have a definite importance in membrane properties upon peptide
      adsorption. 

PMID- 23860210
TI  - Risk factors for maternal and fetal outcome in pregnancy complicated by Ebstein
      anomaly.
AB  - OBJECTIVE: The goal of the study was to examine risks in pregnancy in patients
      with Ebstein anomaly. STUDY DESIGN: Data were examined retrospectively for 13
      patients (27 pregnancies, 21 live births) with Ebstein anomaly during pregnancy
      who were treated at our institution from 1985 to 2011. The associated anomalies
      in these patients were atrial septal defect (ASD) (n = 4) and the Wolff-Parkinson
      White syndrome (n = 6). RESULTS: Before pregnancy, 2 patients underwent ASD
      closure and 1 received tricuspid valve replacement (TVR). In all patients, the
      cardiothoracic ratio increased from 55.1 at conception to 57.0 during pregnancy
      and 58.0 postpartum (P < .05). Cesarean sections were performed in 3 cases: 1
      with ventricular tachycardia and orthopnea (New York Heart Association [NYHA]
      III) preterm; at full term, and the third in a patient with a mechanical
      tricuspid valve who developed maternal cerebellum hemorrhage at 27 weeks. The
      baby died of prematurity in the third case. In all other cases (20 of 21),
      neonatal prognoses were good without congenital heart diseases. There were 6
      spontaneous abortions. Recurrent paroxysmal supraventricular tachycardia occurred
      during pregnancy in 2 cases and was treated with adenosine triphosphate or
      verapamil. In 17 pregnancies, NYHA remained in class I and all had full-term
      vaginal delivery. CONCLUSION: Maternal and fetal outcomes are good in patients
      with Ebstein anomaly and NYHA class I. However, pregnancy in Ebstein anomaly can
      be complicated with tachyarrhythmia or cardiac failure. In post-TVR cases,
      meticulous care is required for these complications during pregnancy and
      delivery.

PMID- 23860212
TI  - Acute fatty liver of pregnancy: clinical outcomes and expected duration of
      recovery.
AB  - OBJECTIVE: Our aim was to provide a description of clinical and laboratory
      finding: pregnancy outcomes in women with acute fatty liver of pregnancy (AFLP).
      We also characterize the duration of recovery of multiorgan system dysfunction
      that begins after delivery. STUDY DESIGN: All women who were admitted to Parkland
      Hospital with AFLP were identified; their clinical and laboratory findings,
      pregnancy outcomes, and postpartum resolution of AFLP were reviewed. RESULTS:
      Between 1975 and 2012, there were 51 women who were identified to have AFLP. The
      most common complaints were persistent nausea and vomiting (57%), hypertension
      (57%), and abdominal pain (53%). More than 90% of these women had at least 1 of
      these findings or combinations thereof. A combination of hepatic and renal
      dysfunction was nearly universal, but with variable severity. Procoagulant
      synthesis was impaired in more than three-fourths of the women, which served to
      intensify obstetric hemorrhage for which 50% of the 51 women received blood and
      component transfusions. The stillbirth rate was 120 of 1000 pregnancies, and
      there were 2 maternal deaths. Composite recovery times of various markers of
      hepatic and renal function indicated normalization of most laboratory values
      within 7-10 days after delivery. CONCLUSION: The clinical features and laboratory
      findings of women with AFLP derive from the central pathologic process: liver
      failure. After delivery, clinical recovery typically is seen within 3-4 days;
      however, laboratory abnormalities can persist for much longer.

PMID- 23860211
TI  - Laparoendoscopic single-site versus conventional laparoscopic gynecologic
      surgery: a metaanalysis of randomized controlled trials.
AB  - OBJECTIVE: To assess the current evidence regarding the efficiency, safety, and
      potential advantages of laparoendoscopic single-site surgery (LESS) for treating
      gynecologic diseases. STUDY DESIGN: We comprehensively searched PubMed, Embase,
      and the Cochrane Library from their inception to December 2012. Two authors
      screened out duplicates and independently reviewed eligibility of each study. We
      included randomized controlled trials comparing LESS with conventional
      laparoscopy (CL) for treating gynecologic diseases. The primary outcomes were
      perioperative complication rate, conversion rate, postoperative pain, and
      cosmetic satisfaction. RESULTS: We included 6 randomized controlled trials with
      439 participants in the final analysis. There were no significant differences
      between LESS and CL in terms of perioperative complication rate (15.5% and 14.3%;
      risk ratio, 1.11; 95% confidence interval [CI], 0.74-1.67; P = .61), conversion
      rate (3.8% and 1.1%; risk ratio, 2.75; 95% CI, 0.73-10.33; P = .13),
      postoperative pain (weighted mean difference [WMD], -0.22; 95% CI, -1.29 to 0.85;
      P = .68), analgesic requirement (WMD, 0.41; 95% CI, -1.69 to 2.51; P = .70), and
      cosmetic satisfaction (WMD, 0.19; 95% CI, -0.30 to 0.68; P = .46). There were
      also no differences in terms of operative time (P = .65), hemoglobin change (P =
      .23), time to first flatus (P = .17), and length of hospital stay (P = .99)
      between both techniques. CONCLUSION: This metaanalysis provides evidence that
      LESS is comparable in the efficacy and safety, but does not offer potential
      advantage such as better cosmesis and lesser pain compared with CL for treating
      gynecologic diseases.

PMID- 23860209
TI  - Long and short non-coding RNAs as regulators of hematopoietic differentiation.
AB  - Genomic analyses estimated that the proportion of the genome encoding proteins
      corresponds to approximately 1.5%, while at least 66% are transcribed, suggesting
      that many non-coding DNA-regions generate non-coding RNAs (ncRNAs). The relevance
      of these ncRNAs in biological, physiological as well as in pathological processes
      increased over the last two decades with the understanding of their implication
      in complex regulatory networks. This review particularly focuses on the
      involvement of two large families of ncRNAs, namely microRNAs (miRNAs) and long
      non-coding RNAs (lncRNAs) in the regulation of hematopoiesis. To date, miRNAs
      have been widely studied, leading to a wealth of data about processing,
      regulation and mechanisms of action and more specifically, their involvement in
      hematopoietic differentiation. Notably, the interaction of miRNAs with the
      regulatory network of transcription factors is well documented whereas roles,
      regulation and mechanisms of lncRNAs remain largely unexplored in hematopoiesis;
      this review gathers current data about lncRNAs as well as both potential and
      confirmed roles in normal and pathological hematopoiesis. 

PMID- 23860213
TI  - Pre-hospital cardiac arrest in acute coronary syndromes: insights from the global
      registry of acute coronary events and the canadian registry of acute coronary
      events.
AB  - OBJECTIVES: Cardiac arrest in acute coronary syndromes (ACS) is associated with
      high morbidity and mortality. We examined the clinical characteristics,
      contemporary management patterns and outcomes of ACS patients with pre-hospital
      cardiac arrest. METHODS: The Global Registry of Acute Coronary Events and the
      Canadian Registry of Acute Coronary Events enrolled 14,010 ACS patients in 1999
      2008. We compared the clinical characteristics, in-hospital treatment and
      outcomes between patients with and without pre-hospital cardiac arrest. RESULTS:
      Overall, 206 (1.4%) patients had cardiac arrest prior to hospital presentation.
      ACS patients with pre-hospital cardiac arrest were less frequently treated with
      aspirin, beta-blocker, angiotensin-converting enzyme inhibitors, and statins
      within the first 24 h of presentation, but the use of cardiac procedures was
      similar compared to the group without cardiac arrest. Patients with pre-hospital
      cardiac arrest had significantly higher rates of in-hospital adverse events.
      Factors independently associated with pre-hospital cardiac arrest included male
      gender, current smoker status, tachycardia, higher Killip class and ST-segment
      deviation. CONCLUSION: ACS patients with pre-hospital cardiac arrest continue to
      have more in-hospital complications and higher mortality. Their use of evidence
      based medical therapies was lower but the use of cardiac procedures was similar
      compared to the group without cardiac arrest. Better utilization of evidence
      based therapies in these patients may translate into improved outcomes.

PMID- 23860215
TI  - Big data and disruptive innovation in wound care.

PMID- 23860218
TI  - Alliance of wound care stakeholders.

PMID- 23860219
TI  - 2013 "Heads-up": detailed written orders and face-to-face encounters for certain
      durable medical equipment.

PMID- 23860220
TI  - Improvement of periulcer skin condition in venous leg ulcer patients:
      prospective, randomized, controlled, single-blinded clinical trial comparing a
      biosynthetic cellulose dressing with a foam dressing.
AB  - OBJECTIVES: The aim of this study was to investigate the influence of a
      biosynthetic cellulose wound dressing (BWD) to stimulate wound healing in
      patients with a venous leg ulcer on periulcer skin condition when compared with
      standard care using a foam dressing. METHODS: Each patient with a venous ulcer
      received compression therapy with a short stretch bandage system and either a BWD
      + foam (study group [SG]) or foam (control group [CG]). Periulcer skin condition
      was compared with the untreated lower leg skin and the forearm skin, using
      noninvasive parameters, comparing day 0 versus day 28 results. Ulcers were
      further evaluated for healing rate. The study period was 28 days, and the follow
      up period was 12 weeks. Fifty patients were recruited to the study, of which N =
      46 (SG, n = 26; CG, n = 20) completed the 28-day study period and were included
      in the analysis. RESULTS: The BWD showed a more improved periulcer skin condition
      versus the CG. Transepidermal water loss was significantly less in the SG (P =
      .003), as well as the results shown with the chromatometer (P =. 05). Ulcer
      healing rate was also statistically significant in favor of the SG (P = .0001).
      CONCLUSION: Treatment for the BWD + foam group was shown to be safe and
      significantly improved periwound skin condition, leading to more expeditious
      wound healing than treatment with foam alone.

PMID- 23860221
TI  - Reliability and validity of the revised photographic wound assessment tool on
      digital images taken of various types of chronic wounds.
AB  - OBJECTIVE: The objective of this study was to examine the validity and
      reliability of the revised Photographic Wound Assessment Tool (revPWAT) on
      digital images taken of various types of chronic, healing wounds. SETTING: This
      multicenter trial was performed in a variety of settings where chronic wounds are
      assessed. PARTICIPANTS: A total of 206 different photographs taken of 68
      individuals with 95 chronic wounds of various etiologies were reviewed in this
      study. Wound etiologies included people with venous/arterial leg wounds (n = 13),
      diabetic foot wounds (n = 18), pressure ulcers (n = 32), and wounds of other
      etiologies (n = 5). MAIN OUTCOME MEASURES: An initial wound assessment using the
      revPWAT was performed at the bedside, and 3 digital photographs were taken-2
      within 72 hours when no change had occurred, and a third was taken 3.5 to 6 weeks
      later. MAIN RESULTS: The revPWAT scores derived from photographs assessed by the
      same rater on different occasions and by different raters showed moderate to
      excellent intrarater intraclass correlation coefficients (ICCs) (ICC = 0.52
      0.93), as well as test-retest (ICC = 0.86-0.90) and interrater (ICC = 0.71)
      reliability. There was excellent agreement between bedside assessments and
      assessments using photographs (ICC = 0.89). CONCLUSION: The revPWAT is a valid
      and reliable tool to assess chronic wounds of various etiologies where digital
      images are viewed.

PMID- 23860222
TI  - Pressure ulcer-related pain in nursing home residents with cognitive impairment.
AB  - PURPOSE: To enhance the learner's competence by providing research about pressure
      ulcer-related pain in nursing home residents with cognitive impairment. TARGET
      AUDIENCE: This continuing education activity is intended for physicians and
      nurses with an interest in skin and wound care. OBJECTIVES: After participating
      in this educational activity, the participant should be better able to:1. Explain
      this study's methodology and tools.2. Predict levels of pressure ulcer pain in a
      nursing home population with dementia. ABSTRACT OBJECTIVE: The objective of this
      study was to examine how pain is reported in cognitively impaired nursing home
      residents with pressure ulcers using the Minimum Data Set 2.0 data set. The study
      design was cross-sectional, comparative stratified by 3 levels of cognitive
      impairment and 4 stages of PrUs. PARTICIPANTS: There were 56,577 participants in
      the study.

PMID- 23860223
TI  - Pressure ulcer evidence-based treatment pathway integrated with evidence-based
      decisions: part 2.

PMID- 23860224
TI  - High-throughput screening normalized to biological response: application to
      antiviral drug discovery.
AB  - The process of conducting cell-based phenotypic screens can result in data sets
      from small libraries or portions of large libraries, making accurate hit picking
      from multiple data sets important for efficient drug discovery. Here, we describe
      a screen design and data analysis approach that allow for normalization not only
      between quadrants and plates but also between screens or batches in a robust,
      quantitative fashion, enabling hit selection from multiple data sets. We
      independently screened the MicroSource Spectrum and NCI Diversity Set II
      libraries using a cell-based phenotypic high-throughput screening (HTS) assay
      that uses an interferon-stimulated response element (ISRE)-driven luciferase
      reporter assay to identify interferon (IFN) signal enhancers. Inclusion of a per
      plate, per-quadrant IFN dose-response standard curve enabled conversion of ISRE
      activity to effective IFN concentrations. We identified 45 hits based on a
      combined z score >=2.5 from the two libraries, and 25 of 35 available hits were
      validated in a compound concentration-response assay when tested using fresh
      compound. The results provide a basis for further analysis of chemical structure
      in relation to biological function. Together, the results establish an HTS method
      that can be extended to screening for any class of compounds that influence a
      quantifiable biological response for which a standard is available. 

PMID- 23860225
TI  - Nuclear expression of glioma-associated oncogene homolog 1 and nuclear factor
      kappaB is associated with a poor prognosis of pancreatic cancer.
AB  - OBJECTIVE: We investigated the association of the hedgehog pathway with nuclear
      factor (NF)-kappaB and clinical outcomes in pancreatic cancer patients. METHODS:
      We analyzed tissue samples for the expression of NF-kappaB (RelA/p65), sonic
      hedgehog (Shh) and glioma-associated oncogene homolog 1 (Gli1) by
      immunohistochemistry and investigated their expression in association with
      clinical outcomes. RESULTS: Eighty-one patients with pancreatic cancer were
      investigated. Expression of Shh and nuclear expression of Gli1 and NF-kappaB were
      found in 63 of 66 (96%), 28 of 68 (41%) and 22 of 68 cases (32%), respectively.
      Nuclear Gli1 expression was closely associated with nuclear expression of NF
      kappaB (p < 0.001). Patients with nuclear Gli1 had significantly worse prognoses
      than those without (median survival 7.9 vs. 13.9 months; p = 0.009). Similarly,
      patients with nuclear expression of NF-kappaB had shorter overall survival than
      those with negative or cytoplasmic expression of NF-kappaB (median survival 5.5
      vs. 13.9 months; p < 0.001). Shh expression had no prognostic significance. In
      the multivariate analysis, NF-kappaB nuclear expression was closely associated
      with unfavorable overall survival (p = 0.02). CONCLUSION: Our results indicate
      that nuclear expression of Gli1 or NF-kappaB is a strong predictor of poor
      prognosis in pancreatic cancer. Additional investigation of the biologic
      significance of this association is warranted.

PMID- 23860226
TI  - A carbon-fiber electrode array for long-term neural recording.
AB  - OBJECTIVE: Chronic neural recording in behaving animals is an essential method
      for studies of neural circuit function. However, stable recordings from small,
      densely packed neurons remains challenging, particularly over time-scales
      relevant for learning. APPROACH: We describe an assembly method for a 16-channel
      electrode array consisting of carbon fibers (<5 um diameter) individually
      insulated with Parylene-C and fire-sharpened. The diameter of the array is
      approximately 26 um along the full extent of the implant. MAIN RESULTS: Carbon
      fiber arrays were tested in HVC (used as a proper name), a song motor nucleus, of
      singing zebra finches where individual neurons discharge with temporally precise
      patterns. Previous reports of activity in this population of neurons have
      required the use of high impedance electrodes on movable microdrives. Here, the
      carbon fiber electrodes provided stable multi-unit recordings over time-scales of
      months. Spike-sorting indicated that the multi-unit signals were dominated by
      one, or a small number of cells. Stable firing patterns during singing confirmed
      the stability of these clusters over time-scales of months. In addition, from a
      total of 10 surgeries, 16 projection neurons were found. This cell type is
      characterized by sparse stereotyped firing patterns, providing unambiguous
      confirmation of single cell recordings. SIGNIFICANCE: Carbon fiber electrode
      bundles may provide a scalable solution for long-term neural recordings of
      densely packed neurons.

PMID- 23860227
TI  - How experience shapes memory for faces: an event-related potential study on the
      own-age bias.
AB  - Young adults more accurately remember own-age than older faces. We tested whether
      this own-age bias (OAB) is reduced by increased experience. Young experts
      (geriatric nurses) and controls performed a recognition experiment with young and
      old faces. Critically, while control participants demonstrated better memory for
      young faces, no OAB was observed in the experts. Event-related potentials
      revealed larger N170 and P2 amplitudes for young than old faces in both groups,
      suggesting no group differences during early perceptual processing. At test, N250
      repetition effects were more anteriorily distributed for own- than other-age
      faces in control participants, whereas experts showed no corresponding effects. A
      larger late positive component (LPC) for old than young faces was observed in
      controls, but not in experts. Larger LPCs may reflect prolonged stimulus
      processing compromising memory retrieval. In sum, experience with other-age faces
      does not affect early perceptual processing, but modulates later stages related
      to memory retrieval. 

PMID- 23860228
TI  - Laparoscopic ventral hernia repair in obese patients under spinal anesthesia.
AB  - PURPOSE: The aim of the present study was to evaluate the feasibility and
      efficacy of laparoscopic ventral hernia repair under spinal anesthesia in obese
      patients (BMI > 30 kg/m(2)). METHODS: From January 2007 to February 2010, 23
      obese patients had their elective laparoscopic ventral hernia repair under spinal
      anesthesia. We looked primarily for intra-operative incidences as well as
      immediate postoperative complications. Long term results and especially
      recurrences were also to be evaluated. RESULTS: Median operative time was 55 min
      (range 20-100). Intraoperatively, six patients (26%) complained of shoulder pain,
      three patients (13%) developed bradycardia and two (8.7%) hypotension.
      Postoperatively, nausea and/or vomiting were recorded in four patients (17.4%),
      four patients (17.4%) experienced urinary retention and one patient developed
      wound infection. Median pain score at 4th, 8th and 24th postoperative hour was
      0.5 (0-5), 1.5 (0-6), and 1.5 (0-5) respectively. The median length of hospital
      stay was one day (1-2). At a median follow up of 39 months, one patient was
      diagnosed with a recurrence. CONCLUSION: Spinal anesthesia for LVHR in obese
      patients (BMI > 30 kg/m(2)) proved an efficient and safe alternative to general
      anesthesia in the given patient sample.

PMID- 23860229
TI  - Analysis of transcript and metabolite levels in Italian rice (Oryza sativa L.)
      cultivars subjected to osmotic stress or benzothiadiazole treatment.
AB  - One of the major objectives of rice (Oryza sativa L.) breeding programs is the
      development of new varieties with higher tolerance/resistance to both abiotic and
      biotic stresses. In this study, Italian rice cultivars were subjected to osmotic
      stress or benzothiadiazole (BTH) treatments. An analysis of the expression of
      selected genes known to be involved in the stress response and (1)H nuclear
      magnetic resonance ((1)H NMR) metabolic profiling were combined with multivariate
      statistical analyses to elucidate potential correlations between gene expression
      or metabolite content and observed tolerant/resistant phenotypes. We observed
      that the expression of three chosen genes (two WRKY genes and one peroxidase
      encoding gene) differed between susceptible and resistant cultivars in response
      to BTH treatments. Moreover, the analysis of metabolite content, in particular in
      the osmotic stress experiment, enabled discrimination between selected cultivars
      based on differences in the accumulation of some primary metabolites, primarily
      sugars. This research highlights the potential usefulness of this approach to
      characterise rice varieties based on transcriptional or metabolic changes due to
      adverse environmental conditions.

PMID- 23860231
TI  - Cloning and expression analysis of transketolase gene in Cucumis sativus L.
AB  - Transketolase (TK, EC 2.2.1.1) is a key enzyme in the photosynthetic carbon
      reduction cycle (Calvin cycle). A full-length cDNA encoding transketolase (TK,
      designated as CsTK) was isolated from cucumber leaves (Cucumis sativa L. cv
      'Jinyou 3') by RT-PCR and RACE. The cDNA contained 2368 nucleotides with a
      complete open reading frame (ORF) of 2229 nucleotides, which was predicted to
      encode a peptide of 742 amino acids. Expression analysis by real-time PCR and
      western blot revealed that TK mRNA was abundant in cucumber leaves and detectable
      in stems, fruits and roots. TK activity and the gene expression at the mRNA and
      protein levels was higher in mid-position leaves (4th apical leaves) than in
      upper position leaves (1st) and base position leaves (12th). The diurnal
      variation of CsTK expression and TK activity in the optimal functional leaf (4th
      leaf) was a single-peak curve, and the peak appeared at 14:00 on a sunny day. Low
      temperature (5  degrees C) and low light (100 MUmol m(-2) s(-1)) induced CsTK
      expression, but the expression level decreased after 24 h of chilling stress.
      Over-expression of CsTK increased the TK activity, mRNA abundance and activities
      of other main enzymes in Calvin cycle, and net photosynthetic rate (Pn) in
      transgenic cucumber leaves. Transgenic plants showed a higher ratio of female
      flower and yield relative to the wild type (WT) plants. The decreases in Pn and
      carboxylation efficiency (CE) were less in transgenic plants than that in WT
      during low temperature and low light intensity. 

PMID- 23860230
TI  - Up-regulation and interaction of the plasma membrane H(+)-ATPase and the 14-3-3
      protein are involved in the regulation of citrate exudation from the broad bean
      (Vicia faba L.) under Al stress.
AB  - Our previous study showed that citrate excretion coupled with a concomitant
      release of protons was involved in aluminum (Al) resistance in the broad bean.
      Furthermore, genes encoding plasma membrane (PM) H(+)-ATPase (vha2) and the 14-3
      3 protein (vf14-3-3b) were up-regulated by Al in Al-resistant (YD) broad bean
      roots. In this study, the roles of PM H(+)-ATPase (E.C. 3.6.3.6) and the 14-3-3
      protein in the regulation of citrate secretion were further investigated in Al
      resistant (YD) and Al-sensitive (AD) broad bean cultivars under Al stress. The
      results showed that greater citrate exudation was positively correlated with
      higher activities of PM H(+)-ATPase in roots of YD than AD. Real-time RT-PCR
      analysis revealed that vha2 was clearly up-regulated by Al in YD but not in AD
      roots, whereas the transcription levels of vf14-3-3b were elevated in a time
      dependent manner in both YD and AD roots. Immunoprecipitation and Western
      analysis suggested that phosphorylation and interaction with the vf14-3-3b
      protein of the VHA2 were enhanced in YD roots but not in AD roots with increasing
      Al treatment time. Fusicoccin or adenosine 5'-monophosphate increased or
      decreased the interaction between the phosphorylated VHA2 and the vf14-3-3b
      protein, followed by an enhancement or reduction of the PM H(+)-ATPase activity
      and citrate exudation in both cultivars under Al stress conditions, respectively.
      Taken together, these results suggested that Al enhanced the expression and
      interaction of the PM H(+)-ATPase and the 14-3-3 protein, which thereby led to
      higher activity of the PM H(+)-ATPase and more citrate exudation from YD plants. 

PMID- 23860232
TI  - Postzygotic isolation involves strong mitochondrial and sex-specific effects in
      Tigriopus californicus, a species lacking heteromorphic sex chromosomes.
AB  - Detailed studies of the genetics of speciation have focused on a few model
      systems, particularly Drosophila. The copepod Tigriopus californicus offers an
      alternative that differs from standard animal models in that it lacks
      heteromorphic chromosomes (instead, sex determination is polygenic) and has
      reduced opportunities for sexual conflict, because females mate only once.
      Quantitative trait loci (QTL) mapping was conducted on reciprocal F2 hybrids
      between two strongly differentiated populations, using a saturated linkage map
      spanning all 12 autosomes and the mitochondrion. By comparing sexes, a possible
      sex ratio distorter was found but no sex chromosomes. Although studies of
      standard models often find an excess of hybrid male sterility factors, we found
      no QTL for sterility and multiple QTL for hybrid viability (indicated by non
      Mendelian adult ratios) and other characters. Viability problems were found to be
      stronger in males, but the usual explanations for weaker hybrid males (sex
      chromosomes, sensitivity of spermatogenesis, sexual selection) cannot fully
      account for these male viability problems. Instead, higher metabolic rates may
      amplify deleterious effects in males. Although many studies of standard
      speciation models find the strongest genetic incompatibilities to be nuclear
      nuclear (specifically X chromosome-autosome), we found the strongest deleterious
      interaction in this system was mito-nuclear. Consistent with the snowball theory
      of incompatibility accumulation, we found that trigenic interactions in this
      highly divergent cross were substantially more frequent (>6*) than digenic
      interactions. This alternative system thus allows important comparisons to
      studies of the genetics of reproductive isolation in more standard model systems.

PMID- 23860233
TI  - Genetic connectivity and diversity in inselberg populations of Acacia
      woodmaniorum, a rare endemic of the Yilgarn Craton banded iron formations.
AB  - Historically rare plant species with disjunct population distributions and small
      population sizes might be expected to show significant genetic structure and low
      levels of genetic diversity because of the effects of inbreeding and genetic
      drift. Across the globe, terrestrial inselbergs are habitat for rich, often rare
      and endemic flora and are valuable systems for investigating evolutionary
      processes that shape patterns of genetic structure and levels of genetic
      diversity at the landscape scale. We assessed genetic structure and levels of
      genetic diversity across the range of the historically rare inselberg endemic
      Acacia woodmaniorum. Phylogeographic and genetic structure indicates that
      connectivity is not sufficient to produce a panmictic population across the
      limited geographic range of the species. However, historical levels of gene flow
      are sufficient to maintain a high degree of adaptive connectivity across the
      landscape. Genetic diversity indicates gene flow is sufficient to largely
      counteract any negative genetic effects of inbreeding and random genetic drift in
      even the most disjunct or smallest populations. Phylogeographic and genetic
      structure, a signal of isolation by distance and a lack of evidence of recent
      genetic bottlenecks suggest long-term stability of contemporary population
      distributions and population sizes. There is some evidence that genetic
      connectivity among disjunct outcrops may be facilitated by the occasional long
      distance dispersal of Acacia polyads carried by insect pollinators moved by
      prevailing winds. 

PMID- 23860234
TI  - Admixture mapping of quantitative traits in Populus hybrid zones: power and
      limitations.
AB  - Uncovering the genetic architecture of species differences is of central
      importance for understanding the origin and maintenance of biological diversity.
      Admixture mapping can be used to identify the number and effect sizes of genes
      that contribute to the divergence of ecologically important traits, even in taxa
      that are not amenable to laboratory crosses because of their long generation time
      or other limitations. Here, we apply admixture mapping to naturally occurring
      hybrids between two ecologically divergent Populus species. We map quantitative
      trait loci for eight leaf morphological traits using 77 mapped microsatellite
      markers from all 19 chromosomes of Populus. We apply multivariate linear
      regression analysis allowing the modeling of additive and non-additive gene
      action and identify several candidate genomic regions associated with leaf
      morphology using an information-theoretic approach. We perform simulation studies
      to assess the power and limitations of admixture mapping of quantitative traits
      in natural hybrid populations for a variety of genetic architectures and modes of
      gene action. Our results indicate that (1) admixture mapping has considerable
      power to identify the genetic architecture of species differences if sample sizes
      and marker densities are sufficiently high, (2) modeling of non-additive gene
      action can help to elucidate the discrepancy between genotype and phenotype
      sometimes seen in interspecific hybrids, and (3) the genetic architecture of leaf
      morphological traits in the studied Populus species involves complementary and
      overdominant gene action, providing the basis for rapid adaptation of these
      ecologically important forest trees. 

PMID- 23860235
TI  - Unravelling stem cell dynamics by lineage tracing.
AB  - During embryonic and postnatal development, the different cells types that form
      adult tissues must be generated and specified in a precise temporal manner.
      During adult life, most tissues undergo constant renewal to maintain homeostasis.
      Lineage-tracing and genetic labelling technologies are beginning to shed light on
      the mechanisms and dynamics of stem and progenitor cell fate determination during
      development, tissue maintenance and repair, as well as their dysregulation in
      tumour formation. Statistical approaches, based on proliferation assays and
      clonal fate analyses, provide quantitative insights into cell kinetics and fate
      behaviour. These are powerful techniques to address new questions and paradigms
      in transgenic mouse models and other model systems. 

PMID- 23860237
TI  - Cell signalling: EGF signalling--it's all in SHC1's timing.

PMID- 23860238
TI  - Differential diagnosis of reactive mesothelial cells and malignant mesothelioma
      cells using the cell proliferation markers minichromosome maintenance protein 7,
      geminin, topoisomerase II alpha and Ki-67.
AB  - OBJECTIVE: The aim of this study was to evaluate whether the immunocytochemical
      expression of cell proliferation markers, such as minichromosome maintenance
      protein 7 (MCM 7), geminin, topoisomerase II alpha (topo IIalpha) and Ki-67,
      which are different types of cell proliferation markers, could be useful for
      their differential diagnosis in reactive mesothelial cells and malignant
      mesothelioma cells obtained from body cavity fluids. STUDY DESIGN: Samples
      diagnosed and later histologically confirmed as reactive mesothelial cells (39
      cases) or malignant mesothelioma (32 cases) in body cavity fluids were examined.
      Immunocytochemical staining of MCM 7, geminin, topo IIalpha and Ki-67 was
      performed with the immunoperoxidase polymer method. RESULTS: Labeling indices
      (LIs) of MCM 7 (cutoff value 20.0%; sensitivity 100%; specificity 100%), geminin
      (cutoff value 4.5%; sensitivity 88.0%; specificity 70.0%), topo IIalpha (cutoff
      value 11.0%; sensitivity 88.0%; specificity 92.0%) and Ki-67 (cutoff value 15.3%;
      sensitivity 78.0%; specificity 79.0%) of malignant mesothelioma cells were
      significantly higher than those of reactive mesothelial cells. CONCLUSION: LIs of
      MCM 7, geminin and topo IIalpha can be reliable tools for the differential
      diagnosis of reactive mesothelial cells and malignant mesothelioma cells.

PMID- 23860236
TI  - Talins and kindlins: partners in integrin-mediated adhesion.
AB  - Integrin receptors provide a dynamic, tightly-regulated link between the
      extracellular matrix (or cellular counter-receptors) and intracellular
      cytoskeletal and signalling networks, enabling cells to sense and respond to
      their chemical and physical environment. Talins and kindlins, two families of
      FERM-domain proteins, bind the cytoplasmic tail of integrins, recruit
      cytoskeletal and signalling proteins involved in mechanotransduction and
      synergize to activate integrin binding to extracellular ligands. New data reveal
      the domain structure of full-length talin, provide insights into talin-mediated
      integrin activation and show that RIAM recruits talin to the plasma membrane,
      whereas vinculin stabilizes talin in cell-matrix junctions. How kindlins act is
      less well-defined, but disease-causing mutations show that kindlins are also
      essential for integrin activation, adhesion, cell spreading and signalling. 

PMID- 23860239
TI  - Antimetastatic effect of halichondramide, a trisoxazole macrolide from the marine
      sponge Chondrosia corticata, on human prostate cancer cells via modulation of
      epithelial-to-mesenchymal transition.
AB  - Halichondramide (HCA), a trisoxazole-containing macrolide isolated from the
      marine sponge Chondrosia corticata has been shown to exhibit cytotoxicity and
      antifungal activities. In our previous study, HCA was also found to exhibit
      antiproliferative activity against a variety of cancer cells. However, the
      precise mechanism of action of HCA in the antitumor activity remains to be
      elucidated. In the present study, we identified the antimetastatic activity of
      HCA in the highly metastatic PC3 human prostate cancer cells. HCA showed potent
      growth inhibitory activity of the PC3 cells with an IC50 value of 0.81 uM.
      Further analysis revealed that HCA suppressed the expression of a potential
      metastatic biomarker, phosphatase of regenerating liver-3 (PRL-3), in PC3 cells.
      The suppression of PRL-3 by HCA sequentially down-regulates the expression of
      phosphoinositide 3-kinase (PI3K) subunits p85 and p110. The antimetastatic effect
      of HCA was also correlated with the down-regulation of matrix metalloproteases
      (MMPs) and the modulation of cadherin switches N-cadherin and E-cadherin. In
      addition, HCA also effectively suppressed the migration and invasion of PC3
      cells. These findings suggest that halichondramide might serve as a potential
      inhibitor of tumor cell metastasis with the modulation of PRL-3. 

PMID- 23860240
TI  - Effect of grazing-mediated dimethyl sulfide (DMS) production on the swimming
      behavior of the copepod Calanus helgolandicus.
AB  - Chemical interactions play a fundamental role in the ecology of marine foodwebs.
      Dimethyl sulfide (DMS) is a ubiquitous marine trace gas that acts as a bioactive
      compound by eliciting foraging behavior in a range of marine taxa including the
      copepod Temora longicornis. Production of DMS can rapidly increase following
      microzooplankton grazing on phytoplankton. Here, we investigated whether grazing
      induced DMS elicits an increase in foraging behavior in the copepod Calanus
      helgolandicus. We developed a semi-automated method to quantify the effect of
      grazing-mediated DMS on the proportion of the time budget tethered females
      allocate towards slow swimming, typically associated with feeding. The pooled
      data showed no differences in the proportion of the 25 min time budget allocated
      towards slow swimming between high (23.6 +/- 9.74%) and low (29.1 +/- 18.33%) DMS
      treatments. However, there was a high degree of variability between behavioral
      responses of individual copepods. We discuss the need for more detailed species
      specific studies of individual level responses of copepods to chemical signals at
      different spatial scales to improve our understanding of chemical interactions
      between copepods and their prey. 

PMID- 23860241
TI  - Parathyrsoidins A-D, four new sesquiterpenoids from the soft coral Paralemnalia
      thyrsoides.
AB  - Four new nardosinane-type sesquiterpenoids, parathyrsoidins A-D (1-4) were
      isolated from the soft coral Paralemnalia thyrsoides. The structures of
      parathyrsoidins A-D (1-4) were determined by extensive spectral analysis and
      their cytotoxicity against selected cancer cell lines as well as antiviral
      activity against human cytomegalovirus (HCMV) were evaluated in vitro. 

PMID- 23860242
TI  - Clinical management of autoimmune biliary diseases.
AB  - Autoimmune biliary disease is an umbrella term that encompasses several distinct
      entities such as primary sclerosing cholangitis, primary biliary cirrhosis,
      autoimmune hepatitis and overlap syndromes. The general approach to the diagnosis
      of these disorders involves investigating symptomatic patients presenting with a
      cholestatic biochemical profile. Asymptomatic patients are often diagnosed during
      investigation of other accompanying or discrete diseases. The distinction between
      the various entities is necessary for directing clinical management in this group
      of patients with an underlying autoimmune pathophysiology. Goals of management
      comprise treating symptoms, preventing complications and suppressing the
      underlying pathogenetic processes. Liver transplantation plays a vital role in
      the management of this group of patients and has shown a dramatic improvement in
      outcomes. Medical therapies such as ursodeoxycholic acid have shown mixed effects
      with excellent outcomes in primary biliary cirrhosis and less impressive results
      in primary sclerosing cholangitis. In this manuscript we aim to discuss in detail
      the management of these autoimmune biliary disorders and describe the effects of
      different therapies on outcomes on the different subsets of patients. 

PMID- 23860244
TI  - Large agminated cellular 'plaque-type' blue nevus surrounding the ear: a case and
      review.
AB  - Large or giant cellular blue nevi are usually congenital and represent a
      challenge for the physician. Close anatomic structures may be altered by the size
      of the moles. In this article, we report the case of an uncommon large,
      agminated, cellular blue nevus of the 'plaque type' in a 42-year-old female. Due
      to the risks of malignant melanoma development on a large or giant blue nevus, we
      highlight the importance of proper histopathological diagnosis. Furthermore,
      because of the possibility that the nevus may invade the bone and cerebral
      tissues, we discuss the indication of a radiological diagnosis. The accurate
      correlation to clinical and histopathological findings and appropriate
      multidisciplinary management can save the lives of patients.

PMID- 23860243
TI  - Inhibition of peroxisomal hydroxypyruvate reductase (HPR1) by tyrosine nitration.
AB  - BACKGROUND: Protein tyrosine nitration is a post-translational modification (PTM)
      mediated by nitric oxide-derived molecules. Peroxisomes are oxidative organelles
      in which the presence of nitric oxide (NO) has been reported. METHODS: We studied
      peroxisomal nitroproteome of pea leaves by high-performance liquid chromatography
      with tandem mass spectrometry (LC-MS/MS) and proteomic approaches. RESULTS:
      Proteomic analysis of peroxisomes from pea leaves detected a total of four nitro
      tyrosine immunopositive proteins by using an antibody against nitrotyrosine. One
      of these proteins was found to be the NADH-dependent hydroxypyruvate reductase
      (HPR). The in vitro nitration of peroxisomal samples caused a 65% inhibition of
      HPR activity. Analysis of recombinant peroxisomal NADH-dependent HPR1 activity
      from Arabidopsis in the presence of H2O2, NO, GSH and peroxynitrite showed that
      the ONOO(-) molecule caused the highest inhibition of activity (51% at 5mM SIN
      1), with 5mM H2O2 having no inhibitory effect. Mass spectrometric analysis of the
      nitrated recombinant HPR1 enabled us to determine that, among the eleven tyrosine
      present in this enzyme, only Tyr-97, Tyr-108 and Tyr-198 were exclusively
      nitrated to 3-nitrotyrosine by peroxynitrite. Site-directed mutagenesis confirmed
      Tyr198 as the primary site of nitration responsible for the inhibition on the
      enzymatic activity by peroxynitrite. CONCLUSION: These findings suggest that
      peroxisomal HPR is a target of peroxynitrite which provokes a loss of function.
      GENERAL SIGNIFICANCE: This is the first report demonstrating the peroxisomal NADH
      dependent HPR activity involved in the photorespiration pathway is regulated by
      tyrosine nitration, indicating that peroxisomal NO metabolism may contribute to
      the regulation of physiological processes under no-stress conditions.

PMID- 23860245
TI  - Understanding hospital cafeterias: results from cafeteria manager interviews.
AB  - OBJECTIVE: To describe the characteristics, nutrition-related knowledge,
      practices, and attitudes of staff managing cafeterias in New York City (NYC)
      hospitals. METHODS: An in-person survey was administered over 7 months to
      cafeteria managers from hospitals participating in the NYC Department of Health
      and Mental Hygiene's Healthy Hospital Food Initiative. The survey assessed
      nutrition knowledge and attitudes; hospital cafeteria practices; and nutrition
      standards and policies. The majority of questions required a yes or no response,
      followed by an open-ended request for details related to the response. Other
      questions were multiple choice or used 5-point Likert scales to measure
      respondent perceptions. RESULTS: Seventeen cafeteria managers completed the
      survey. Less than a third of respondents had training in nutrition, and less than
      a quarter of hospitals followed nutrition standards for food offered in the
      cafeteria. Most respondents thought cafeterias could play a role in reducing
      sodium consumption, yet less than half correctly identified the largest sources
      of sodium in the average diet. The most commonly cited limitation to making
      healthy changes in the cafeteria was perceived lack of demand for healthy
      foods/customer support. CONCLUSION: Characteristics, nutrition knowledge,
      practices, and attitudes of hospital cafeteria managers vary. Communication with
      consumers and education of staff who lack training and experience in nutrition
      may be important focus areas for hospitals looking to improve their food
      environment.

PMID- 23860246
TI  - Gastrointestinal adverse events after dual antiplatelet therapy: clopidogrel is
      safer than ticagrelor, but prasugrel data are lacking or inconclusive.
AB  - Current guidelines offer a choice of P2Y12 receptor antagonist among clopidogrel,
      prasugrel or ticagrelor on top of aspirin (ASA) for dual antiplatelet therapy
      (DAPT) in patients after acute coronary syndromes (ACS). However, the comparative
      risks of gastrointestinal (GI) adverse events during DAPT are not clear. Two
      large ACS trials (TRITON and PLATO) provide a valuable opportunity to directly
      match the risks of GI complications among current antiplatelet regimens. We
      compared the rates of GI adverse events after prasugrel and ticagrelor versus
      clopidogrel based on the Food and Drug Administration (FDA) clinical safety
      reviews. When compared with ticagrelor, clopidogrel is safer with regard to GI
      related risks including fewer overall GI/anal bleeding events and spontaneous GI
      hemorrhagic episodes, less nausea, vomiting, dyspepsia and diarrhea, and a lower
      rate of presence of Helicobacter pylori. Among GI symptoms, only constipation was
      more common after clopidogrel than following ticagrelor. There were extrahepatic
      risks observed with ticagrelor but not with prasugrel when compared to
      clopidogrel. Prasugrel unquestionably caused more bleeding from the GI tract and
      GI malignancies than clopidogrel. However, the entire spectrum of GI effects of
      prasugrel is much less well known and mostly based on sponsor analysis rather
      than FDA-verified numbers. Among 3 DAPT options on top of ASA, clopidogrel seems
      to represent the safest alternative, although comprehensive data on direct
      prasugrel-associated GI effects are lacking or inconclusive. 

PMID- 23860247
TI  - Impact of early parenteral nutrition on muscle and adipose tissue compartments
      during critical illness.
AB  - OBJECTIVE: The goal of enhanced nutrition in critically ill patients is to
      improve outcome by reducing lean tissue wasting. However, such effect has not
      been proven. This study aimed to assess the effect of early administration of
      parenteral nutrition on muscle volume and composition by repeated quantitative
      CT. DESIGN: A preplanned substudy of a randomized controlled trial (Early
      Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill
      Patients [EPaNIC]), which compared early initiation of parenteral nutrition when
      enteral nutrition was insufficient (early parenteral nutrition) with tolerating a
      pronounced nutritional deficit for 1 week in ICU (late parenteral nutrition).
      Late parenteral nutrition prevented infections and accelerated recovery. SETTING:
      University hospital. PATIENTS: Fifteen EPaNIC study neurosurgical patients
      requiring prescheduled repeated follow-up CT scans and six healthy volunteers
      matched for age, gender, and body mass index. INTERVENTION: Repeated abdominal
      and femoral quantitative CT images were obtained in a standardized manner on
      median ICU day 2 (interquartile range, 2-3) and day 9 (interquartile range, 8
      10). Intramuscular, subcutaneous, and visceral fat compartments were delineated
      manually. Muscle and adipose tissue volume and composition were quantified using
      standard Hounsfield Unit ranges. MEASUREMENTS AND MAIN RESULTS: Critical illness
      evoked substantial loss of femoral muscle volume in 1 week's time, irrespective
      of the nutritional regimen. Early parenteral nutrition reduced the quality of the
      muscle tissue, as reflected by the attenuation, revealing increased intramuscular
      water/lipid content. Early parenteral nutrition also increased the volume of
      adipose tissue islets within the femoral muscle compartment. These changes in
      skeletal muscle quality correlated with caloric intake. In the abdominal muscle
      compartments, changes were similar, albeit smaller. Femoral and abdominal
      subcutaneous adipose tissue compartments were unaffected by disease and
      nutritional strategy. CONCLUSIONS: Early parenteral nutrition did not prevent the
      pronounced wasting of skeletal muscle observed over the first week of critical
      illness. Furthermore, early parenteral nutrition increased the amount of adipose
      tissue within the muscle compartments.

PMID- 23860248
TI  - Blood purification and mortality in sepsis: a meta-analysis of randomized trials.
AB  - OBJECTIVES: Although blood purification improves outcomes in animal studies of
      sepsis, results of clinical trials have been mixed. We conducted a systematic
      review and meta-analysis of randomized trials to determine the association
      between various blood purification techniques and all-cause mortality in humans
      with sepsis. DATA SOURCES: We searched for relevant studies in MEDLINE, EMBASE,
      and the Cochrane Library database from January 1966 to May 2012. STUDY SELECTION:
      Inclusion required a diagnosis of sepsis and comparison of blood purification
      techniques including hemofiltration, hemoperfusion, plasma exchange, or
      hemodialysis with no blood purification (control group). DATA EXTRACTION: Two
      authors independently selected studies and extracted data. Summary statistics,
      risk ratios, and CIs were calculated using random-effects modeling. Study quality
      was assessed using Jadad score, and publication bias was assessed using funnel
      plots and Egger's statistic. DATA SYNTHESIS: Overall, blood purification
      decreased mortality compared with no blood purification (35.7% vs 50.1%; risk
      ratio, 0.69 [95% CI, 0.56-0.84]; p<0.001; 16 trials, n=827). However, these
      results were driven mainly by hemoperfusion (risk ratio, 0.63 [95% CI, 0.50
      0.80]; p<0.001; 10 trials, n=557) and plasma exchange (risk ratio, 0.63 [95% CI,
      0.42-0.96]; p=0.03; two trials, n=128). Pooling of all trials of blood
      purification for treatment of sepsis was no longer associated with lower
      mortality (risk ratio, 0.89 [95% CI, 0.71-1.13]; p=0.36; eight trials, n=457)
      after excluding trials using polymyxin B hemoperfusion. CONCLUSIONS: Blood
      purification techniques including hemoperfusion, plasma exchange, and
      hemofiltration with hemoperfusion were associated with lower mortality in
      patients with sepsis. These results were mainly influenced by studies using
      polymyxin B hemoperfusion from Japan.

PMID- 23860250
TI  - Design of novel Geldanamycin analogue hsp90 alpha-inhibitor in silico for breast
      cancer therapy.
AB  - BACKGROUND: Geldanamycin, which is one of the most potent and effective hsp90
      alpha inhibitor until date, is normally used to target breast cancer. Inhibition
      of hsp90 alpha leads to the degradation of client proteins involved in the
      initiation and progress of breast cancer pathogenesis. Hence, Geldanamycin has
      been widely pursued as a treatment option for breast cancer. However, it failed
      to move into the clinics due to the toxicity associated with its solubility.
      Geldanamycin was modified chemically to develop 17-N-allylamino-17
      demethoxygeldanamycin (17-AAG) and later 17-Dimethylaminoethylamino-17
      demethoxygeldanamycin (17-DMAG), which have higher solubility and lesser
      toxicity. Nonetheless, in order to achieve highest efficacy against breast
      cancer, a more potent, soluble and least toxic hsp90 alpha inhibitors need to be
      developed. HYPOTHESIS: We hypothesize that designing a novel Geldanamycin
      analogue with increased affinity and efficacy would provide a probability of
      having less toxic effect in the therapy of breast cancer. We also hypothesize
      that hsp90 alpha forms a multi-chaperone complex with hsp70 and hsp40 and thus
      assist the folding and maturation of number of client proteins including cellular
      p53. We further hypothesize that the higher binding affinity of the novel
      Geldanamycin analogue for hsp90 alpha triggers the degradation of nonfunctional
      mutant p53 by cellular proteasomes. EXPERIMENTAL DESIGN: Ten different
      Geldanamycin analogues were designed using Marvinsketch software. Binding
      affinity of hsp90 alpha and its complex (hsp70, hsp40) with wild type p53 and
      mutant p53 were determined using Hex 6.3. Binding affinities of ten different
      analogues for hsp90 alpha were determined by estimating binding energies of
      molecules using Hex 6.3 and Autodock 4.0 softwares. RESULTS: The estimation of
      molecular docking energies using Hex 6.3 and Autodock 4.0 software proved that
      Analogue 9 was the best hsp90 alpha inhibitor among all ten analogues designed
      and the existing inhibitors. Following hsp90 alpha inhibition using Analogue 9
      and subsequent docking results using Hex 6.3 software showed less binding
      affinity of Analogue 9 for mutant p53 than the wild version, suggesting the
      increased chance of the degradation of mutant p53 by cellular machines.
      CONCLUSIONS: Based on our findings, we propose Analogue 9 to be the more
      efficient hsp90 alpha inhibitor than existing inhibitors. Furthermore, the
      chemical synthesis of Analogue 9 at the laboratory scale and successful in vitro
      and in vivo studies in breast cancer model would lead the compound into the
      clinical stage.

PMID- 23860251
TI  - Empathy as a sense of autonomy.
AB  - In this paper, we examine Jaspers' ambiguous approach to empathy. We start by
      situating Jaspers' notion of empathic understanding in the context of
      contemporary philosophical discussions of empathy. We distinguish a
      phenomenological approach to interpersonal understanding from two influential
      accounts of other minds, namely, theory-theory and simulation-theory, and then we
      contrast Jaspers' notion of empathic understanding with a phenomenological
      approach. We distinguish two basic kinds of empathy, a prereflective nonconative
      kind and a more reflective conative kind. Then we argue that Jaspers'
      philosophical conception of human nature as restless and undefinable autonomy
      makes him reject any kind of comprehensive attempt to understand other people. We
      try to make sense of this rejection by discussing the epistemological and ethical
      nature of his notorious 'theorem of incomprehensibility'. This eventually leads
      us, by way of conclusion, to sketch a method required for making sense of those
      experiences that cannot be understood via ordinary empathy. The key notion of
      this method is called 'second-order empathy'.

PMID- 23860249
TI  - From endoplasmic reticulum to mitochondria: absence of the Arabidopsis ATP
      antiporter endoplasmic Reticulum Adenylate Transporter1 perturbs
      photorespiration.
AB  - The carrier Endoplasmic Reticulum Adenylate Transporter1 (ER-ANT1) resides in the
      endoplasmic reticulum (ER) membrane and acts as an ATP/ADP antiporter. Mutant
      plants lacking ER-ANT1 exhibit a dwarf phenotype and their seeds contain reduced
      protein and lipid contents. In this study, we describe a further surprising
      metabolic peculiarity of the er-ant1 mutants. Interestingly, Gly levels in leaves
      are immensely enhanced (26*) when compared with that of wild-type plants. Gly
      accumulation is caused by significantly decreased mitochondrial glycine
      decarboxylase (GDC) activity. Reduced GDC activity in mutant plants was
      attributed to oxidative posttranslational protein modification induced by
      elevated levels of reactive oxygen species (ROS). GDC activity is crucial for
      photorespiration; accordingly, morphological and physiological defects in er-ant1
      plants were nearly completely abolished by application of high environmental
      CO(2) concentrations. The latter observation demonstrates that the absence of ER
      ANT1 activity mainly affects photorespiration (maybe solely GDC), whereas basic
      cellular metabolism remains largely unchanged. Since ER-ANT1 homologs are
      restricted to higher plants, it is tempting to speculate that this carrier
      fulfils a plant-specific function directly or indirectly controlling cellular ROS
      production. The observation that ER-ANT1 activity is associated with cellular ROS
      levels reveals an unexpected and critical physiological connection between the ER
      and other organelles in plants.

PMID- 23860252
TI  - Propensity-based matching between esophagogastric cancer patients who had surgery
      and who declined surgery after preoperative chemoradiation.
AB  - BACKGROUND: Trimodality therapy (TMT; chemoradiation plus surgery) has level-1
      evidence for survival advantage for TMT-eligible esophagogastric cancer patients.
      Some patients, however, decline surgery after preoperative chemoradiation. The
      question of which patient should have esophagectomy and which one should not is
      unlikely to be answered by a prospective comparison; therefore, we matched the
      clinical covariates of several patients who had surgery with those who declined
      surgery (DS). METHODS: Between 2002 and 2011, we identified 623 patients in our
      databases. Of 623 patients, 244 patients had TMT and 61 TMT-eligible patients
      were in the DS group. Using the propensity-score method, we matched 16 covariates
      between 36 DS patients and 36 TMT patients. RESULTS: Baseline characteristics
      between the two groups were balanced (p = NS). The median overall survival times
      were: 57.9 months (95% CI: 27.7 to not applicable, NA) for the DS group and 50.8
      months (95% CI: 30.7 to NA) for the TMT group (p = 0.28). The median relapse-free
      survival times were: 18.5 (95% CI: 11.5-30.4) for the DS group and 26.5 months
      (95% CI: 15.5-NA) for the TMT group (p = 0.45). Eleven (31%) of 36 patients in
      the DS group had salvage surgery. CONCLUSIONS: Our results are intriguing but
      skewed by the patients who had salvage surgery in the DS group. Until highly
      reliable predictive models are developed for esophageal preservation, TMT must be
      encouraged for all TMT-eligible gastroesophageal cancer patients.

PMID- 23860253
TI  - The calcium feedback loop and T cell activation: how cytoskeleton networks
      control intracellular calcium flux.
AB  - During T cell activation, the engagement of a T cell with an antigen-presenting
      cell (APC) results in rapid cytoskeletal rearrangements and a dramatic increase
      of intracellular calcium (Ca(2+)) concentration, downstream to T cell antigen
      receptor (TCR) ligation. These events facilitate the organization of an
      immunological synapse (IS), which supports the redistribution of receptors,
      signaling molecules and organelles towards the T cell-APC interface to induce
      downstream signaling events, ultimately supporting T cell effector functions.
      Thus, Ca(2+) signaling and cytoskeleton rearrangements are essential for T cell
      activation and T cell-dependent immune response. Rapid release of Ca(2+) from
      intracellular stores, e.g. the endoplasmic reticulum (ER), triggers the opening
      of Ca(2+) release-activated Ca(2+) (CRAC) channels, residing in the plasma
      membrane. These channels facilitate a sustained influx of extracellular Ca(2+)
      across the plasma membrane in a process termed store-operated Ca(2+) entry
      (SOCE). Because CRAC channels are themselves inhibited by Ca(2+) ions, additional
      factors are suggested to enable the sustained Ca(2+) influx required for T cell
      function. Among these factors, we focus here on the contribution of the actin and
      microtubule cytoskeleton. The TCR-mediated increase in intracellular Ca(2+)
      evokes a rapid cytoskeleton-dependent polarization, which involves actin
      cytoskeleton rearrangements and microtubule-organizing center (MTOC)
      reorientation. Here, we review the molecular mechanisms of Ca(2+) flux and
      cytoskeletal rearrangements, and further describe the way by which the
      cytoskeletal networks feedback to Ca(2+) signaling by controlling the spatial and
      temporal distribution of Ca(2+) sources and sinks, modulating TCR-dependent
      Ca(2+) signals, which are required for an appropriate T cell response. This
      article is part of a Special Issue entitled: Reciprocal influences between cell
      cytoskeleton and membrane channels, receptors and transporters. Guest Editor:
      Jean Claude Herve. 

PMID- 23860254
TI  - Alamethicin in bicelles: orientation, aggregation, and bilayer modification as a
      function of peptide concentration.
AB  - Alamethicin is a 19-amino-acid residue hydrophobic peptide of the peptaibol
      family that has been the object of numerous studies for its ability to produce
      voltage-dependent ion channels in membranes. In this work, for the first time
      electron paramagnetic resonance spectroscopy was applied to study the interaction
      of alamethicin with oriented bicelles. We highlighted the effects of increasing
      peptide concentrations on both the peptide and the membrane in identical
      conditions, by adopting a twofold spin labeling approach, placing a nitroxide
      moiety either on the peptide or on the phospholipids. The employment of bicelles
      affords additional spectral resolution, thanks to the formation of a
      macroscopically oriented phase that allows to gain information on alamethicin
      orientation and dynamics. Moreover, the high viscosity of the bicellar solution
      permits the investigation of the peptide aggregation properties at physiological
      temperature. We observed that, at 35 degrees C, alamethicin adopts a
      transmembrane orientation with the peptide axis forming an average angle of 25
      degrees  with respect to the bilayer normal. Moreover, alamethicin maintains its
      dynamics and helical tilt constant at all concentrations studied. On the other
      hand, by increasing the peptide concentration, the bilayer experiences an
      exponential decrease of the order parameter, but does not undergo micellization,
      even at the highest peptide to lipid ratio studied (1:20). Finally, the
      aggregation of the peptide at physiological temperature shows that the peptide is
      monomeric at peptide to lipid ratios lower than 1:50, then it aggregates with a
      rather broad distribution in the number of peptides (from 6 to 8) per oligomer. 

PMID- 23860255
TI  - The physiological role of cardiac cytoskeleton and its alterations in heart
      failure.
AB  - Cardiac muscle cells are equipped with specialized biochemical machineries for
      the rapid generation of force and movement central to the work generated by the
      heart. During each heart beat cardiac muscle cells perceive and experience
      changes in length and load, which reflect one of the fundamental principles of
      physiology known as the Frank-Starling law of the heart. Cardiac muscle cells are
      unique mechanical stretch sensors that allow the heart to increase cardiac
      output, and adjust it to new physiological and pathological situations. In the
      present review we discuss the mechano-sensory role of the cytoskeletal proteins
      with respect to their tight interaction with the sarcolemma and extracellular
      matrix. The role of contractile thick and thin filament proteins, the elastic
      protein titin, and their anchorage at the Z-disc and M-band, with associated
      proteins are reviewed in physiologic and pathologic conditions leading to heart
      failure. This article is part of a Special Issue entitled: Reciprocal influences
      between cell cytoskeleton and membrane channels, receptors and transporters.
      Guest Editor: Jean Claude Herve 

PMID- 23860257
TI  - A finite rate of innovation algorithm for fast and accurate spike detection from
      two-photon calcium imaging.
AB  - OBJECTIVE: Inferring the times of sequences of action potentials (APs) (spike
      trains) from neurophysiological data is a key problem in computational
      neuroscience. The detection of APs from two-photon imaging of calcium signals
      offers certain advantages over traditional electrophysiological approaches, as up
      to thousands of spatially and immunohistochemically defined neurons can be
      recorded simultaneously. However, due to noise, dye buffering and the limited
      sampling rates in common microscopy configurations, accurate detection of APs
      from calcium time series has proved to be a difficult problem. APPROACH: Here we
      introduce a novel approach to the problem making use of finite rate of innovation
      (FRI) theory (Vetterli et al 2002 IEEE Trans. SIGNAL PROCESS: 50 1417-28). For
      calcium transients well fit by a single exponential, the problem is reduced to
      reconstructing a stream of decaying exponentials. Signals made of a combination
      of exponentially decaying functions with different onset times are a subclass of
      FRI signals, for which much theory has recently been developed by the signal
      processing community. Main results. We demonstrate for the first time the use of
      FRI theory to retrieve the timing of APs from calcium transient time series. The
      final algorithm is fast, non-iterative and parallelizable. Spike inference can be
      performed in real-time for a population of neurons and does not require any
      training phase or learning to initialize parameters. SIGNIFICANCE: The algorithm
      has been tested with both real data (obtained by simultaneous electrophysiology
      and multiphoton imaging of calcium signals in cerebellar Purkinje cell
      dendrites), and surrogate data, and outperforms several recently proposed methods
      for spike train inference from calcium imaging data.

PMID- 23860256
TI  - Membrane protein structure determination - the next generation.
AB  - The field of Membrane Protein Structural Biology has grown significantly since
      its first landmark in 1985 with the first three-dimensional atomic resolution
      structure of a membrane protein. Nearly twenty-six years later, the crystal
      structure of the beta2 adrenergic receptor in complex with G protein has
      contributed to another landmark in the field leading to the 2012 Nobel Prize in
      Chemistry. At present, more than 350 unique membrane protein structures solved by
      X-ray crystallography (http://blanco.biomol.uci.edu/mpstruc/exp/list, Stephen
      White Lab at UC Irvine) are available in the Protein Data Bank. The advent of
      genomics and proteomics initiatives combined with high-throughput technologies,
      such as automation, miniaturization, integration and third-generation
      synchrotrons, has enhanced membrane protein structure determination rate. X-ray
      crystallography is still the only method capable of providing detailed
      information on how ligands, cofactors, and ions interact with proteins, and is
      therefore a powerful tool in biochemistry and drug discovery. Yet the growth of
      membrane protein crystals suitable for X-ray diffraction studies amazingly
      remains a fine art and a major bottleneck in the field. It is often necessary to
      apply as many innovative approaches as possible. In this review we draw attention
      to the latest methods and strategies for the production of suitable crystals for
      membrane protein structure determination. In addition we also highlight the
      impact that third-generation synchrotron radiation has made in the field,
      summarizing the latest strategies used at synchrotron beamlines for screening and
      data collection from such demanding crystals. This article is part of a Special
      Issue entitled: Structural and biophysical characterisation of membrane protein
      ligand binding. 

PMID- 23860258
TI  - Surfactant protein D, soluble intercellular adhesion molecule-1 and high
      sensitivity C-reactive protein as biomarkers of chronic obstructive pulmonary
      disease.
AB  - OBJECTIVE: The aim of this study was to estimate the serum levels of surfactant
      protein D (SP-D), soluble intercellular adhesion molecule-1 (sICAM-1), and high
      sensitivity C-reactive protein (hs-CRP) in patients with chronic obstructive
      pulmonary disease (COPD) and to assess the correlation of these indices with COPD
      severity. SUBJECTS AND METHODS: This analytic cross-sectional study was carried
      out on 64 COPD male patients, and 26 apparently healthy age-matched males as a
      control. Chest X-ray, spirometry and arterial blood gases were done for only COPD
      patients. Serum levels of SP-D, sICAM-1 and hs-CRP were determined by enzyme
      linked immunosorbent assay in both patient and control groups. RESULTS: The serum
      levels of SP-D, sICAM-1 and hs-CRP were significantly higher in COPD patients
      than controls (p < 0.001 for each). Also, these biomarkers were significantly
      higher in stages III and IV compared to either stage I or II (p < 0.01 for each).
      SP-D was significantly positively correlated with sICAM-1 and hs-CRP (r = 515, p
      < 0.001; r = 501, p < 0.001, respectively) and negatively correlated with PaO2 (r
      = -0.651, p < 0.001) and all parameters of spirometry. CONCLUSION: SP-D, sICAM
      and hs-CRP were significantly higher in COPD patients in comparison with
      controls. Moreover, SP-D, sICAM-1, and hs-CRP were significantly negatively
      correlated with FEV1%. Accordingly, estimation of these biochemical indices may
      be used as biomarkers for assessment of COPD severity.

PMID- 23860260
TI  - Hmgb1 can facilitate activation of the matrilin-1 gene promoter by Sox9 and L
      Sox5/Sox6 in early steps of chondrogenesis.
AB  - The architectural high mobility group box 1 (Hmgb1) protein acts as both a
      nuclear and an extracellular regulator of various biological processes, including
      skeletogenesis. Here we report its contribution to the evolutionarily conserved,
      distinctive regulation of the matrilin-1 gene (Matn1) expression in amniotes. We
      previously demonstrated that uniquely assembled proximal promoter elements
      restrict Matn1 expression to specific growth plate cartilage zones by allowing
      varying doses of L-Sox5/Sox6 and Nfi proteins to fine-tune their Sox9-mediated
      transactivation. Here, we dissected the regulatory mechanisms underlying the
      activity of a conserved distal promoter element 1. We show that this element
      carries three Sox-binding sites, works as an enhancer in vivo, and allows
      promoter activation by the Sox5/6/9 chondrogenic trio. In early steps of
      chondrogenesis, declining Hmgb1 expression overlaps with the onset of Sox9
      expression. Unlike repression in late steps, Hmgb1 overexpression in early
      chondrogenesis increases Matn1 promoter activation by the Sox trio, and forced
      Hmgb1 expression in COS-7 cells facilitates induction of Matn1 expression by the
      Sox trio. The conserved Matn1 control elements bind Hmgb1 and SOX9 with opposite
      efficiency in vitro. They show higher HMGB1 than SOX trio occupancy in
      established chondrogenic cell lines, and HMGB1 silencing greatly increases MATN1
      and COL2A1 expression. Together, these data thus suggest a model whereby Hmgb1
      helps recruit the Sox trio to the Matn1 promoter and thereby facilitates
      activation of the gene in early chondrogenesis. We anticipate that Hmgb1 may
      similarly affect transcription of other cartilage-specific genes. 

PMID- 23860261
TI  - GAGA factor repression of transcription is a rare event but the negative
      regulation of Trl is conserved in Drosophila species.
AB  - GAGA is a highly conserved Drosophila transcription factor encoded by the
      Trithorax-like (Trl) gene. While GAGA usually activates transcription, it
      represses its own promoter. Here we show that GAGA-mediated repression of Trl is
      conserved between two distant Drosophila species. A detailed promoter study
      showed that GAGA repressive activity can't be attributed to any discrete element
      in the Trl promoter. Genome-wide analysis of the transcriptome in S2 cells
      indicated that repression of Trl is very likely unique, being GAGA factor a
      transactivator for all the other promoters. Taken together, our results suggest a
      new mechanism to explain GAGA-mediated repression that involves a dose-dependent
      change in the architecture of the Trl promoter. 

PMID- 23860259
TI  - Peptidylarginine deiminases in citrullination, gene regulation, health and
      pathogenesis.
AB  - Peptidylarginine deiminases are a family of enzymes that mediate post
      translational modifications of protein arginine residues by deimination or
      demethylimination to produce citrulline. In vitro, the activity of PADs is
      dependent on calcium and reductive reagents carrying a free sulfhydryl group. The
      discovery that PAD4 can target both arginine and methyl-arginine for
      citrullination about 10years ago renewed our interest in studying this family of
      enzymes in gene regulation and their physiological functions. The deregulation of
      PADs is involved in the etiology of multiple human diseases, including cancers
      and autoimmune disorders. There is a growing effort to develop isoform specific
      PAD inhibitors for disease treatment. However, the regulation of the activity of
      PADs in vivo remains largely elusive, and we expect that much will be learned
      about the role of these enzymes in a normal life cycle and under pathology
      conditions. 

PMID- 23860262
TI  - Longitudinal course and risk factors for fatigue in adolescents: the mediating
      role of sleep disturbances.
AB  - OBJECTIVES: This study (1) examines fatigue over 1 year in adolescents with
      chronic pain (n = 61) and depressive disorders (n = 51) compared with healthy
      adolescents (n = 60), (2) identifies longitudinal risk factors, and (3) tests
      sleep disturbances as a mediator between depression and fatigue. METHODS:
      Adolescents completed questionnaires at baseline, 6, and 12 months. Mixed effects
      models examined associations between risk factors and fatigue; structural
      equation modeling assessed contemporaneous and longitudinal mediation. RESULTS:
      Results revealed fatigue persisted at 1 year follow-up, with adolescents in the
      clinical samples experiencing greater fatigue than healthy youth at all time
      points (ps < .001). Age, baseline depression, and baseline sleep disturbances
      predicted longitudinal fatigue for the total sample (ps < .05), with variation in
      predictors by subgroup. Sleep quality mediated the contemporaneous effects of
      depression on fatigue in the clinical samples (ps < .05). CONCLUSIONS: Findings
      underscore the longitudinal course of fatigue and suggest that improving sleep
      disturbances may reduce fatigue in clinical samples.

PMID- 23860263
TI  - Growth temperature-induced changes in biomass accumulation, photosynthesis and
      glutathione redox homeostasis as influenced by hydrogen peroxide in cucumber.
AB  - Hydrogen peroxide (H2O2) and glutathione (GSH) are involved in the stress
      response in plants. To elucidate the role of H2O2 in the acclimation of CO2
      assimilation under sub- or supra-optimal growth temperatures, we examined the
      effect and interaction of H2O2 manipulation on the photosynthetic metabolism of
      cucumber plants (Cucumis sativus L.) grown under five temperature regimes
      spanning above and below the optimal growth temperature; 11/9, 18/15, 25/20,
      32/27, and 39/33  degrees C (day/night), with or without dimethylthiourea (DMTU)
      or H2O2 treatment. As expected, exposure to sub- or supra-optimal growth
      temperatures resulted in decreased plant growth, associated with a decline in CO2
      assimilation (Asat), Rubisco content, and activities of enzymes involved in the
      CO2 assimilation, as well as a decrease in the ratio of reduced (GSH) to oxidized
      (GSSG) glutathione (GSH/GSSG). Foliar application of H2O2 promoted, whilst DMTU
      retarded the capacity of plants to acclimate to non-optimal growth temperatures;
      this was consistently shown in altered activity of redox-sensitive enzymes
      involved in CO2 assimilation. These results strongly suggest that the influence
      of growth temperature on CO2 assimilation was primarily targeted at the
      activities of the redox-sensitive enzymes of CO2 assimilation. Meanwhile, the
      data suggest that the cellular H2O2 level is an important signal for the
      glutathione-dependent regulation of redox-sensitive enzymes of CO2 assimilation
      in cucumber plants.

PMID- 23860264
TI  - Factors associated with remaining in a skilled nursing facility for over 90 days
      from admission: residents' participation in therapy and desire to return to the
      community.
AB  - BACKGROUND: To identify the factors associated with stay in a skilled nursing
      facility (SNF) among new enrollees who did not fully participate in therapy
      sessions. METHODS: Data (n = 36,133) were obtained from the Minimum Data Set
      version 2.0 in the state of Michigan in 2009. Study participants were new SNF
      enrollees (n = 699) who did not fully participate in therapy sessions despite
      their desire to return to the community. Multivariate logistic regressions were
      performed to identify factors contributing to remaining in a nursing home for 91
      days or longer. RESULTS: New SNF enrollees were more likely to remain in nursing
      home when they were depressed (odds ratio [OR] = 1.41; 95% confidence interval
      [CI], 1.09-2.08; P = .01), experiencing delirium (OR = 3.20; 95% CI, 1.48-5.92; P
      < .001), were not in pain (OR = 0.83; 95% CI, 0.60-0.95; P = .03), or in less
      complex care (OR = 0.57; 95% CI, 0.44-0.81; P < .01). CONCLUSIONS: A higher
      number of new SNF enrollees than previously reported were likely to stay in
      nursing homes (28.0%). Depression and delirium were associated with stay in an
      SNF, while pain and higher complexity of care were associated with returning to
      the community.

PMID- 23860265
TI  - Exercise for falls and fracture prevention in long term care facilities: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The overall effect of exercise on falls and fracture prevention in
      long term care facilities remains controversial. In this study, we aimed to
      analyze the impact and the characteristics of the most effective physical
      exercise regime to prevent falls and fractures in this particular setting.
      METHODS: Our search looked for randomized controlled trials published in English
      language between January 1974 and June 2012 in electronic databases including
      MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials,
      Physiotherapy Evidence Database, Allied and Complementary Medicine, and
      Occupational Therapy Seeker that specifically tested the effect of exercise on
      falls and/or fractures in long term care residents. Two investigators
      independently extracted data and assessed study quality. The Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was applied
      throughout the systematic review and meta-analysis. RESULTS: Twelve studies were
      selected that included 1292 participants. Most of the participants were women
      (68%) with a mean age of 83.9 +/- 9 years. The intervention period was between 3
      and 24 months, and the most commonly performed intervention were balance and
      resistance training exercises. Meta-analysis showed that exercise has a
      preventive effect on falls (risk ratio [RR] = 0.77, 95% confidence interval [CI],
      0.64-0.92; I(2) = 72.18, P < .001). This effect was stronger when mixing several
      types of exercises (RR = 0.71, 95% CI, 0.55-0.90; I(2) = 72.07, P < .001), for at
      least 1-3 months (RR = 0.65, 95% CI, 0.43-0.98; I(2) = 61.821; P < .001) or for
      more than 6 months (RR = 0.70, 95% CI, 0.56-0.87; I(2) = 68.407; P < .001), with
      a frequency of at least 2-3 times per week (RR = 0.74, 95% CI, 0.60-0.91; I(2) =
      68.092; P < .001). Physical exercise did not show any effect on fracture
      prevention (RR = 0.57, 95% CI, 0.21-1.57; I(2) = 48.805). CONCLUSIONS: Combined,
      frequent and long-term exercise programs are effective to prevent falls in long
      term care facilities. No effect of exercise on fracture prevention was observed
      in this population.

PMID- 23860266
TI  - Using mPINC data to measure breastfeeding support for hospital employees.
AB  - BACKGROUND: Employer support is important for mothers, as returning to work is a
      common reason for discontinuing breastfeeding. This article explores support
      available to breastfeeding employees of hospitals that provide maternity care.
      OBJECTIVES: This study aimed to describe the prevalence of 7 different types of
      worksite support and changes in these supports available to breastfeeding
      employees at hospitals that provide maternity care from 2007 to 2011. METHODS:
      Hospital data from the 2007, 2009, and 2011 Centers for Disease Control and
      Prevention Survey on Maternity Practices in Infant Nutrition and Care (mPINC)
      were analyzed. Survey respondents were asked if the hospital provides any of the
      following supports to hospital staff: (1) a designated room to express milk, (2)
      on-site child care, (3) an electric breast pump, (4) permission to use existing
      work breaks to express milk, (5) a breastfeeding support group, (6) lactation
      consultant/specialist available for consult, and (7) paid maternity leave other
      than accrued vacation or sick leave. This study was exempt from ethical approval
      because it was a secondary analysis of a publicly available dataset. RESULTS: Of
      the 7 worksite supports in hospitals measured, 6 increased and 1 decreased from
      2007 to 2011. Across all survey years, more than 70% of hospitals provided
      supports for expressing breast milk, whereas less than 15% provided direct access
      to the breastfeeding child through on-site child care, and less than 35% offered
      paid maternity leave. Results differed by region and hospital size and type. In
      2011, only 2% of maternity hospitals provided all 7 worksite supports; 40%
      provided 5 or more. CONCLUSION: The majority of maternity care hospitals (> 70%)
      offer breastfeeding supports that allow employees to express breast milk.
      Supports that provide direct access to the breastfeeding child, which would allow
      employees to breastfeed at the breast, and access to breastfeeding support groups
      are much less frequent than other supports, suggesting opportunities for
      improvement.

PMID- 23860267
TI  - A case study of a late preterm infant's transition to full at-breast feedings at
      4 months of age.
AB  - Breast milk intake is recommended for late preterm infants. Many mothers provide
      expressed breast milk during hospitalization and anticipate transitioning their
      late preterm infant to full feedings at-breast after discharge. However, some
      infants take months to transition to full feedings at-breast. This article
      describes the case of a mother and her 35-week infant who transitioned to full
      feeding at-breast at 4 months after discharge. The clinical strategies to
      maintain maternal milk supply, use of hospital-grade scale, and importance of
      professional and community lactation support are discussed. 

PMID- 23860268
TI  - WITHDRAWN: Identification of meteorin and metrnl as two novel pro-differentiative
      adipokines: Possible roles in controlling adipogenesis and insulin sensitivity.
AB  - BBRC has been targeted by a scheme to defraud our editors, reviewers and readers
      with submission of a manuscript with falsified author and institutional
      information and therefore wholly unverifiable scientific claims. The manuscript
      has been withdrawn. We consider such abuse of the editorial and peer review
      system with the submission of fictional content unethical and it wastes the
      valuable time of all those who contributed to the evaluation of this manuscript.
      We are currently exploring which local authorities would have jurisdiction, and
      will with such authorities explore the question of whether this also constitutes
      a criminal case of internet fraud and we anticipate turning over to them all of
      the information we have been able to attain from EES regarding the source of the
      fraudulent submission.

PMID- 23860269
TI  - SUMOylation of damaged DNA-binding protein DDB2.
AB  - Damaged DNA-binding protein (DDB) is a heterodimer composed of two subunits, p127
      and p48, which have been designated DDB1 and DDB2, respectively. DDB2 recognizes
      and binds to UV-damaged DNA during nucleotide excision repair. Here, we
      demonstrated that DDB2 was SUMOylated in a UV-dependent manner, and its major
      SUMO E3 ligase was PIASy as determined by RNA interference-mediated knockdown.
      The UV-induced physical interaction between DDB2 and PIASy supported this notion.
      PIASy knockdown reduced the removal of cyclobutane pyrimidine dimers (CPDs) from
      total genomic DNA, but did not affect that of 6-4 pyrimidine pyrimidone
      photoproducts (6-4PPs). Thus, DDB2 plays an indispensable role in CPD repair, but
      not in 6-4PP repair, which is consistent with the observation that DDB2 was
      SUMOylated by PIASy. These results suggest that the SUMOylation of DDB2
      facilitates CPD repair. 

PMID- 23860270
TI  - Activation of Aro80 transcription factor by heat-induced aromatic amino acid
      influx in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, transcription of ARO9 and ARO10 genes, involved in
      the catabolism of aromatic amino acids, is activated by Aro80 transcription
      factor in response to aromatic amino acids. Here we show that the transcription
      of ARO9 and ARO10 is also induced by heat shock in an Aro80-dependent manner.
      However, heat shock-related signaling pathways including PKA, PKC, and HOG
      pathways are not involved in the heat shock activation of Aro80. We elucidate
      that heat-induced increase in aromatic amino acid influx can lead to the inducer
      dependent activation of Aro80 upon heat shock. Known aromatic amino acid
      permeases play an insignificant role in the heat-induced expression of ARO9 and
      ARO10, suggesting that an increase in plasma membrane fluidity might be
      responsible for the influx of aromatic amino acids during heat shock stress. 

PMID- 23860271
TI  - Effect of lameness and lesion specific causes of lameness on time budgets of
      dairy cows at pasture and when housed.
AB  - The aim of the study was to investigate the effect of lameness and specific
      causes of lameness on standing time, number of lying bouts and test day yield
      (TDY) in cows at pasture and cows which were housed. Data were collected from 200
      cows from 10 farms where cows were at pasture and 200 cows from 10 farms where
      they were housed. Each farm was visited twice over 3 days between May and August
      (autumn and winter) of 2009. At the first visit, 10 lame cows, all with
      locomotion score (LS) 3, and 10 non-lame cows, all with LS 1, were selected per
      farm. Electronic data loggers were positioned on one hind leg of each cow to
      record standing time and transitions. These were removed 3 days later at the
      second visit. There was no significant difference in standing time between housed
      and pasture-based cows but lame cows stood for a mean 1.75 (SE 0.36) h/day less
      than non-lame cows in both systems. Cows with sole damage, wall damage, misshapen
      feet and infectious lameness all stood for less time than non-lame cows. Housed
      cows had a mean 1.4 more lying bouts per day than cows at pasture. Lame cows at
      pasture had 1.2 more lying bouts per day than non-lame cows but housed lame
      cattle had 0.8 fewer lying bouts than non-lame housed cattle, so overall the
      number of lying bouts in lame cows, housed or at pasture, was similar. The only
      lesion associated with a change in the number of lying bouts was sole damage with
      a mean 1.1 more lying bouts per day across systems than non-lame cows. Lame cows
      had lower TDY than non-lame cows and TDY was reduced more in lame cows when TDY
      was greater. In conclusion, standing times were similar in cows at pasture and in
      housed cows, but lying bouts were different. However, given the associations
      between standing time, lying bouts and TDY the results might be most strongly
      influenced by TDY, rather than system. Future studies investigating the impact of
      lameness on cow behaviour by system in cows with similar and a range of TDY would
      be informative.

PMID- 23860272
TI  - The effect of Amifostine prophylaxis on bone densitometry, biomechanical strength
      and union in mandibular pathologic fracture repair.
AB  - BACKGROUND: Pathologic fractures (Fx) of the mandibles are severely debilitating
      consequences of radiation (XRT) in the treatment of craniofacial malignancy. We
      have previously demonstrated Amifostine's effect (AMF) in the remediation of
      radiation-induced cellular damage. We posit that AMF prophylaxis will preserve
      bone strength and drastically reverse radiotherapy-induced non-union in a murine
      mandibular model of pathologic fracture repair. MATERIALS AND METHODS: Twenty
      nine rats were randomized into 3 groups: Fx, XRT/Fx, and AMF/XRT/Fx. A
      fractionated human equivalent dose of radiation was delivered to the left
      hemimandibles of XRT/Fx and AMF/XRT/Fx. AMF/XRT/Fx was pre-treated with AMF. All
      groups underwent left mandibular osteotomy with external fixation and setting of
      a 2.1mm fracture gap post-operatively. Utilizing micro-computed tomography and
      biomechanical testing, the healed fracture was evaluated for strength. RESULTS:
      All radiomorphometrics and biomechanical properties were significantly diminished
      in XRT/Fx compared to both Fx and AMF/XRT/Fx. No difference was demonstrated
      between Fx and AMF/XRT/Fx in both outcomes. CONCLUSION: Our investigation
      establishes the significant and substantial capability of AMF prophylaxis to
      preserve and enhance bone union, quality and strength in the setting of human
      equivalent radiotherapy. Such novel discoveries establish the true potential to
      utilize pharmacotherapy to prevent and improve the treatment outcomes of
      radiation-induced late pathologic fractures.

PMID- 23860273
TI  - Trial design and rationale of TY-51924 as a novel Na+/H+ exchanger inhibitor in
      patients with ST-elevation acute myocardial infarction undergoing percutaneous
      coronary intervention.
AB  - BACKGROUND: Reperfusion therapy limits infarct size and improves survival in
      patients with ST-elevation myocardial infarction (STEMI). However, reperfusion
      itself may, in some cases, deteriorate myocardial damage, causing the so-called
      ischemia-reperfusion injury. Activation of the Na(+)/H(+) exchanger (NHE) at the
      time of reperfusion plays an important role in ischemia-reperfusion injury. We
      designed a Phase IIa proof of concept clinical trial to evaluate the potential of
      TY-51924, an NHE inhibitor, as adjunctive therapy to primary percutaneous
      coronary intervention (pPCI) for patients with STEMI. METHODS: This is a
      multicenter, randomized, double-blind, placebo-controlled clinical trial designed
      to evaluate the efficacy and the safety of TY-51924 in patients with first
      anterior STEMI who are undergoing pPCI. Immediately before pPCI, a bolus
      intravenous injection followed by infusion of TY-51924 (up to 30 mg/kg) or
      placebo was administered. Primary endpoints were myocardial salvage index (MSI)
      determined by (201)Tl/(123)I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP)
      dual-isotope single photon emission computed tomography (SPECT) performed 3-5
      days after pPCI, and safety up to 7 days. Secondary endpoints were the degree of
      myocardial injury based on cardiac enzyme release and QRS score by
      electrocardiogram (ECG), cardiac functions determined by SPECT or magnetic
      resonance imaging (MRI), and safety up to 3 months following pPCI. Furthermore,
      MRI studies were also performed where possible 3-7 days and 3 months after pPCI.
      DISCUSSION: The appropriateness of assessing safety and efficacy of TY-51924 as
      adjunctive therapy to pPCI for patients with STEMI will be discussed in this
      study plan.

PMID- 23860274
TI  - Morphology and metal binding characteristics of a natural polymer-kondagogu
      (Cochlospermum gossypium) gum.
AB  - Kondagogu (Cochlospermum gossypium) gum (KG), a natural tree exudate, was
      investigated for its morphological, adsorption and metal interaction behavior
      with various toxic heavy metals (Pb, Cd, Ni, Cr and Fe). SEM, AFM and TEM
      techniques were used to study the morphological changes occurring after metal
      adsorption onto the biopolymer structure. The degree of biosorption of metals on
      KG biopolymer surfaces was assessed by small-angle X-ray scattering analysis.
      EDXA spectrum revealed that the ion-exchange mechanism plays a major role in the
      binding process between KG and metal ions. The higher electron density observed
      in the KG-Cd complex suggests that Cd is strongly bound to KG compared to the
      other metals. This work provides a potential platform for developing a
      hydrocolloid-based nanogel for bioremediation of environmental contaminants. 

PMID- 23860275
TI  - Differential growth inhibitory effects of highly oxygenated guaianolides isolated
      from the Middle Eastern indigenous plant Achillea falcata in HCT-116 colorectal
      cancer cells.
AB  - Medicinal plants play a crucial role in traditional medicine and in the
      maintenance of human health worldwide. Sesquiterpene lactones represent an
      interesting group of plant-derived compounds that are currently being tested as
      lead drugs in cancer clinical trials. Achillea falcata is a medicinal plant
      indigenous to the Middle Eastern region and belongs to the Asteraceae family,
      which is known to be rich in sesquiterpene lactones. We subjected Achillea
      falcata extracts to bioassay-guided fractionation against the growth of HCT-116
      colorectal cancer cells and identified four secotanapartholides, namely 3-beta
      methoxy-isosecotanapartholide (1), isosecotanapartholide (2), tanaphallin (3),
      and 8-hydroxy-3-methoxyisosecotanapartholide (4). Three highly oxygenated
      guaianolides were isolated for the first time from Achillea falcata, namely rupin
      A (5), chrysartemin B (6), and 1beta, 2beta-epoxy-3beta,4alpha,10alpha
      trihydroxyguaian-6alpha,12-olide (7). These sesquiterpene lactones showed no or
      minor cytotoxicity while exhibiting promising anticancer effects against HCT-116
      cells. Further structure-activity relationship studies related the bioactivity of
      the tested compounds to their skeleton, their lipophilicity, and to the type of
      functional groups neighboring the main alkylating center of the molecule.

PMID- 23860276
TI  - Enhanced stability of CaO and/or La2O3 promoted Pd/Al2O3 egg-shell catalysts in
      partial oxidation of methane to syngas.
AB  - An egg-shell Pd/Al2O3 catalyst showed higher activity than a regular Pd/Al2O3
      catalyst in the partial oxidation of methane to syngas, but a common problem of
      this reaction is the catalyst deactivation on stream. We attempted to modify the
      egg-shell catalyst via impregnation with some metal oxide additives. Although the
      addition of MgO did not show any beneficial effect, the addition of CaO and/or
      La2O3 significantly improved the stability due to the suppression of carbon
      deposition and phase transformation of the Al2O3 support. The catalysts were
      characterized by X-ray diffraction (XRD), N2 adsorption-desorption, and
      thermogravimetric analysis (TGA). 

PMID- 23860277
TI  - The genus Gnaphalium L. (Compositae): phytochemical and pharmacological
      characteristics.
AB  - The genus Gnaphalium, a herb distributed worldwide, comprises approximately 200
      species of the Compositae (Asteraceae) family that belongs to the tribe
      Gnaphalieae. Some species are traditionally used as wild vegetables and in folk
      medicine. This review focuses on the phytochemical investigations and biological
      studies of plants from the genus Gnaphalium over the past few decades. More than
      125 chemical constituents have been isolated from the genus Gnaphalium, including
      flavonoids, sesquiterpenes, diterpenes, triterpenes, phytosterols,
      anthraquinones, caffeoylquinic acid derivatives, and other compounds. The
      extracts of this genus, as well as compounds isolated from it, have been
      demonstrated to possess multiple pharmacological activities such as antioxidant,
      antibacterial and antifungal, anti-complement, antitussive and expectorant,
      insect antifeedant, cytotoxic, anti-inflammatory, antidiabetic and
      antihypouricemic properties. The present review compiles the information
      available on this genus because of its relevance to food and ethnopharmacology
      and the potential therapeutic uses of these species. 

PMID- 23860278
TI  - Colour preferences in nest-building zebra finches.
AB  - Some bird species are selective in the materials they choose for nest building,
      preferring, for example, materials of one colour to others. However, in many
      cases the cause of these preferences is not clear. One of those species is the
      zebra finch, which exhibits strong preferences for particular colours of nest
      material. In an attempt to determine why these birds strongly prefer one colour
      of material over another, we compared the preferences of paired male zebra
      finches for nest material colour with their preferences for food of the same
      colours. We found that birds did indeed prefer particular colours of nest
      material (in most cases blue) but that they did not generally prefer food of one
      colour over the other colours. It appears, then, that a preference for one colour
      or another of nest material is specific to the nest-building context. This
      article is part of a Special Issue entitled: insert SI title. 

PMID- 23860279
TI  - The role of pregnenolone sulphate in spatial orientation-acquisition and
      retention: an interplay between cognitive potentiation and mood regulation.
AB  - Neurosteroids can alter neuronal excitability interacting with specific
      neurotransmitter receptors, thus affecting several functions such as cognition
      and emotionality. In this study, we investigated, in adult male rats, the effects
      of the acute administration of pregnenolone-sulfate (PREGS) (10 mg/Kg, s.c.) on
      cognitive processes using the Can test, a non aversive spatial/visual task which
      allows the assessment of spatial information-acquisition during the baseline
      training, and of memory retention in the longitudinal study. Furthermore, on the
      basis of PREGS pharmacological profile, the modulation of depressive-like
      behaviour was also evaluated in the forced swim test (FST). Our results indicate
      that acute PREGS induces: an improvement in spatial orientation-acquisition and
      in reference memory, during the baseline training; a strengthening effect on
      reference and working memory during the longitudinal study. A decrease in
      immobility time in the FST has also been recorded. In conclusion, PREGS exerts
      enhancing properties on acquisition, consolidation and retrieval of spatial
      information, probably due of improved hippocampal-dependent memory processes. The
      additional antidepressant effect observed in the FST can provide further evidence
      in support of the potential of PREGS as a therapeutic tool for the treatment of
      cognitive deficits associated with mood disorders. This article is part of a
      Special Issue entitled: insert SI title.

PMID- 23860280
TI  - The effect of opponent type on human performance in a three-alternative choice
      task.
AB  - Adult participants played computerised games of "Paper Scissors Rock".
      Participants in one group were told that they were playing against the computer,
      and those in the other group were told that they were playing against another
      participant in the adjacent room. The participant who won the most games would
      receive a $50 prize. For both groups however, the opponent's responses (paper,
      scissors, or rock) were generated by the computer, and the distribution of these
      responses was varied across four blocks of 126 trials. Results were analysed
      using the generalised matching law for the three possible pairs of alternatives
      (paper vs. scissors, paper vs. rock, and scissors vs. rock) across all
      participants in each group. Overall, significantly higher estimates of
      sensitivity to the distribution of opponent's responses were obtained from
      participants who were told their opponent was a computer compared to participants
      who were told their opponent was another participant. While adding to the
      existing literature showing that the generalised matching law is an adequate
      descriptor of human three-alternative choice behaviour, these findings show that
      external factors such as perceived opponent type can affect the efficacy of
      reinforcer contingencies on human behaviour. This suggests that generalising the
      results from tasks performed against a computer to real-life human-to-human
      interactions warrants some caution. 

PMID- 23860281
TI  - Differences in responses to repeated fear-relevant stimuli between Nagoya and
      White Leghorn chicks.
AB  - Freezing responses to fearful stimuli are crucial for survival among all animal
      species within a prey-predator system. Generally, the degree of fearfulness
      correlates with intensity, duration, and frequency of freezing behaviours in
      response to fear-relevant stimuli. The present study examines innate fear
      responses to human handling in 144 newly hatched chicks through a tonic
      immobility (TI) test. Two fear responses-freezing duration and number of TI
      inductions-were examined. Individual variations in innate fear were investigated
      in chicks 1-2 days post-hatching when the restraint procedure was successively
      repeated 3 times within each day. Chicks showed sensitivity to fearful stimuli
      and considerable inter-individual variation in freezing duration and number of
      attempts required to induce TI. Moreover, differences were observed between
      breeds; White Leghorn chicks showed relatively low fear levels with gradual
      increases in TI duration, whereas Nagoya chicks showed extended TI duration and
      habituation to fearful stimuli. Our results suggest that TI reactions among newly
      hatched chicks are an innately determined behaviour specific to a breed or strain
      of chicken. Further, fearful responses among newborn chicks are not simple, but
      complex behaviours that involve multiple factors, such as breed-specific
      contextual fear learning and habituation/sensitisation processes. 

PMID- 23860282
TI  - Survival of Vibrio parahaemolyticus and Aeromonas hydrophila in sea bream (Sparus
      aurata) fillets packaged under enriched CO(2) modified atmospheres.
AB  - The ability to survive of two pathogens (Vibrio parahaemolyticus and Aeromonas
      hydrophila) spread over sea bream fillets packaged under different modified
      atmospheres (MAPs) was studied at 0 degrees C and 4 degrees C under refrigerated
      storage. The atmospheres used were 60% CO2/40% N2, 70% CO2/30% N2 and 80% CO2/20%
      N2 and a control batch packaged in air. Head space gas analyses, microbial counts
      and confirming test of pathogenic bacteria were carried out during 16days. The
      results obtained showed that all the modified atmospheres studied were effective
      to reduce the microbial load of sea bream fillets when compared with air packaged
      samples although small differences were found among MAPs. Temperature storage was
      the main factor to reduce microbial growth. V. parahaemolyticus was unable to
      grow at both temperatures, 0 degrees C and 4 degrees C (except air batches) while
      A. hydrophila showed significant growth at 4 degrees C and microbial inactivation
      at 0 degrees C. 

PMID- 23860283
TI  - A pilot study evaluating liquid-based fine needle aspiration cytology of breast
      lesions: a cytomorphological comparison of SurePath(r) liquid-based preparations
      and conventional smears.
AB  - OBJECTIVE: Fine needle aspiration cytology (FNAC) is recommended by the World
      Health Organization as a diagnostic method for breast lesions. The morphological
      interpretation of liquid-based preparations (LBPs) remains a diagnostic challenge
      due to considerably altered cytomorphology. The aim of the current study was to
      compare cytomorphological characteristics of SurePath(r) (SP)-based LBP and
      conventional smear (CS) in breast FNACs. STUDY DESIGN: The study included 77
      benign and 60 malignant breast FNACs obtained by both SP and CS, all with tissue
      confirmation. Cases analyzed with both preparations were reviewed and compared,
      focusing on 10 cytomorphological features. RESULTS: SP aspirates demonstrated
      notable cytomorphological alterations. Among them, a prominent three-dimensional
      configuration of cell clusters and frequent and conspicuous nucleoli were the
      most prominent characteristics of SP compared with CS. Overall diagnostic
      performances were comparable but were slightly lower for SP than CS (diagnostic
      accuracy of two reviewers; 87.6 and 90.5% for SP vs. 91.2 and 92.7% for CS,
      respectively). CONCLUSION: Although the reviewer should be aware of distinctive
      cytomorphological alterations, the SP technique is reliable for the evaluation of
      breast lesions with the advantage of easy interpretation and a diagnostic
      accuracy equivalent to CS.

PMID- 23860284
TI  - Possibility of stretch-shortening cycle movement training using a jump rope.
AB  - Although jumping rope has been said to be a typical stretch-shortening cycle
      movement (SSC) from the dynamic analysis of muscle contraction, there are few
      research reports that focus on this point. Recently, the function of SSC of the
      legs with respect to the jumping movement has been evaluated using the rebound
      jump index (RJ-index). This study aimed to examine the possibility of using rope
      jumping in SSC training by comparing the RJ-index of the rebound jump (standard
      value) and the 2 different methods of rope jumping. The subjects included 76
      healthy young men. Most subjects were involved in routine sports training 2-3
      times per week. They performed the rebound jump (5 consecutive vertical jumps)
      and both a basic and a double-under jump with the jump rope, according to each
      participant's individual style (rhythm or timing). The RJ-index was calculated
      using the ground contact time and the jump height. The reliabilities of the RJ
      index in the basic (intraclass correlation coefficient: 0.85) and double-under
      jump (0.92) were high, and the RJ-index of the latter (1.34 +/- 0.24) was
      significantly higher than that of the former (0.60 +/- 0.21). In the case of a
      group with inferior SSC ability, the RJ-index of the rebound jump only showed a
      significant correlation with the double-under but not with the basic jump. When
      using the RJ-index (1.97 +/- 0.38) of the rebound jump as a criterion, the double
      under-using about 70% of the SSC ability-may be effective for reinforcement of
      SSC ability.

PMID- 23860285
TI  - Kansas squat test: a reliable indicator of short-term anaerobic power.
AB  - The purposes of this study were to establish stability reliability of a measure
      of lower-body anaerobic power, the Kansas squat test (KST), and to compare the
      KST with the commonly used Wingate anaerobic test (WAnT) for lower-body power.
      Fourteen resistance-trained men (mean +/- SD; age = 24.2 +/- 3.6 years) performed
      both the KST and the WAnT twice on separate occasions. The KST consisted of using
      an external dynamometer to measure mean repetition power while performing 15
      repetitions of speed squats using 70% of 1 repetition maximum system mass
      (barbell + body mass), initiating each repetition at 6-second intervals.
      Repetition power, mean power for all 15 repetitions, and % fatigue for the KST
      were all reliable (intraclass correlation coefficient = 0.754-0.937; p <= 0.05).
      There were no differences between tests for the mean power for all repetitions or
      relative fatigue (p <= 0.05) and no significant differences between tests for any
      individual repetition (test * repetition interaction, p < 0.05). Although
      absolute values were different (p > 0.05), significant correlations were found
      between the KST and WAnT for mean (r = 0.752) and maximum (r = 0.775) test powers
      but not for relative fatigue (r = 0.174). Lactate (HLa) responses were greater
      for the WAnT compared with the KST. These data indicate that the KST is reliable
      for resistance-trained men, and that measures of maximum and mean test powers for
      the KST are highly correlated to those values for the WAnT, but fatigue rates and
      HLa responses were not correlated. It appears that the KST is a lifting-specific
      anaerobic power and power endurance test that emphasizes phosphagen metabolism
      and may be used to assess training-induced changes in lower-body power.

PMID- 23860286
TI  - Concurrent validity of the Armour39 heart rate monitor strap.
AB  - New technology offers potential advantages in physically demanding environments
      where convenience and comfort are important and accurate and reliable data
      collection is challenging. Nevertheless, it is important to validate the accuracy
      and reliability of such biological monitoring systems (BMS) before they are
      adopted. The purpose of this investigation was to assess the concurrent validity
      of a new heart rate monitor across a range of exercise intensities and with a
      large and diverse group of male subjects in a large cohort with diverse physical
      fitness characteristics. Seventy-five men (age, 23 +/- 4 years; height, 181 +/- 8
      cm; body mass, 83 +/- 12 kg; estimated V[Combining Dot Above]O2peak, 3.16 +/-
      0.63 [L.min]) volunteered and completed a graded cycle ergometer exercise
      protocol while heart rate was continuously monitored before, during, and after
      exercise with the new device (Armour39) and the gold standard
      (electrocardiogram). The 2-minute stages included sitting, standing, and cycling
      with 35 W increments until volitional fatigue. The coefficient of determination
      between mean heart rate values at each stage was R = 0.99, whereas Pearson
      correlations (r) at each stage were >= 0.99. Heart rates during exercise were
      typically within 1 beat of each other. The Armour39 BMS, therefore, is an
      acceptable means for the valid and reliable determination of heart rate under
      various bodily positions and levels of exertion, including maximal exercise
      intensity.

PMID- 23860287
TI  - Mixed maximal and explosive strength training in recreational endurance runners.
AB  - Supervised periodized mixed maximal and explosive strength training added to
      endurance training in recreational endurance runners was examined during an 8
      week intervention preceded by an 8-week preparatory strength training period.
      Thirty-four subjects (21-45 years) were divided into experimental groups: men (M,
      n = 9), women (W, n = 9), and control groups: men (MC, n = 7), women (WC, n = 9).
      The experimental groups performed mixed maximal and explosive exercises, whereas
      control subjects performed circuit training with body weight. Endurance training
      included running at an intensity below lactate threshold. Strength, power,
      endurance performance characteristics, and hormones were monitored throughout the
      study. Significance was set at p <= 0.05. Increases were observed in both
      experimental groups that were more systematic than in the control groups in
      explosive strength (12 and 13% in men and women, respectively), muscle
      activation, maximal strength (6 and 13%), and peak running speed (14.9 +/- 1.2 to
      15.6 +/- 1.2 and 12.9 +/- 0.9 to 13.5 +/- 0.8 km L h). The control groups showed
      significant improvements in maximal and explosive strength, but Speak increased
      only in MC. Submaximal running characteristics (blood lactate and heart rate)
      improved in all groups. Serum hormones fluctuated significantly in men
      (testosterone) and in women (thyroid stimulating hormone) but returned to
      baseline by the end of the study. Mixed strength training combined with endurance
      training may be more effective than circuit training in recreational endurance
      runners to benefit overall fitness that may be important for other adaptive
      processes and larger training loads associated with, e.g., marathon training.

PMID- 23860288
TI  - Effect of carbohydrate supplementation on the physiological and perceptual
      responses to prolonged tennis match play.
AB  - Carbohydrate supplementation is a popular nutritional practice used in tennis to
      enhance physical capacities, motor-skill performance, and delay fatigue. However,
      the effects of carbohydrate supplementation on physiological and perceptual
      responses during tennis match play are not established. This double blind,
      randomized, placebo (PLA)-controlled crossover study was designed to determine
      the influence of carbohydrate supplementation (0.5 g.kg.h) on glycemia, salivary
      hormones (cortisol and testosterone) concentration, salivary immunoglobulin A
      (IgA) concentration, and rating of perceived exertion (RPE) during 3 hours of
      tennis match play in 12 well-trained tennis players. The only significant
      difference between the 2 conditions was a lower salivary cortisol concentration
      postmatch in the carbohydrate trial (p < 0.05); however, there was a trend for
      higher glucose concentration (p = 0.06) and lower session-RPE (p = 0.08) after
      tennis match play in the carbohydrate condition, which may have some practical
      implications. There was no change in salivary testosterone, salivary IgA, and RPE
      responses during tennis match play between conditions (p > 0.05). These data
      indicate that carbohydrate ingestion during 3 hours of competitive tennis match
      play helps to maintain glycemia and attenuates the increase in salivary cortisol
      concentration compared with PLA.

PMID- 23860289
TI  - The Relationship of Foot Strike Pattern, Shoe Type, and Performance in a 50-km
      Trail Race.
AB  - Recent "in-race" studies have observed the foot strike patterns of runners in
      traditional road marathon races. However, similar studies have not been conducted
      for trail runners, which have been estimated to account for 11% of all runners.
      The purpose of this study was to (a) determine the rear-foot strike (RFS)
      prevalence in a 50-km trail race and compare with traditional road marathon
      races; (b) determine if there is a relationship between foot strike and sex in a
      50-km trail race; and (c) determine if there is a relationship between foot
      strike, shoe type, and performance in a 50-km trail race. One hundred sixty-five
      runners were videotaped at the 8.1-km mark of the 2012 Ice Age Trail 50-km race.
      Foot strike analysis revealed RFS prevalence of 85.1%, less than previously
      reported in traditional road marathon races. There was no relationship found
      between sex and foot strike (p = 0.60). A significant effect of shoe type on foot
      strike (RFS was less common among runners in minimalist shoes, p < 0.01) and
      performance (faster runners were more likely to be wearing minimalist shoes, p <
      0.01) was observed; however, no association between foot strike and performance
      was observed (p = 0.83). This study suggests that most trail runners, albeit less
      than road runners, prefer an RFS pattern, which is accompanied by biomechanical
      consequences unique from a non-RFS pattern and, therefore, likely carries a
      unique injury profile. In addition, the findings in this study suggest that
      minimalist shoes may represent a reasonable training modification to improve
      performance.

PMID- 23860290
TI  - Body composition changes among female NCAA division 1 athletes across the
      competitive season and over a multiyear time frame.
AB  - Body composition can affect athletic performance. Numerous studies have
      documented changes in body composition in female collegiate athletes from pre- to
      postseason; however, longitudinal studies examining changes across years are
      scarce. Therefore, the primary purpose of this study was to assess longitudinal
      body composition changes among female collegiate athletes across 3 years. Two
      hundred twelve female athletes from basketball (BB; n = 38), soccer (SOC; n =
      47), swimming (SW; n = 52), track (sprinters and jumpers; TR; n = 49), and
      volleyball (VB; n = 26) with an initial mean age of 19.2 +/- 1.2 years, height of
      172.4 +/- 8.9 cm, and total mass of 66.9 +/- 9.0 kg had body composition
      assessments using dual-energy x-ray absorptiometry pre- and postseason over 3
      years. A restricted maximum-likelihood linear mixed model regression analysis
      examined body composition differences by sport and year. Changes (p < 0.05) over
      3 years included the following: Lean mass increased in VB from year 1 to 2 (0.7
      kg), year 2 to 3 (1.1 kg), and year 1 to 3 (1.8 kg) and in SW from year 1 to 3
      (0.6 kg); and percent body fat (%BF) increased in BB from year 1 to 3 (1.7%).
      There were no changes in SOC or TR. These results indicate that during their
      college careers, female collegiate athletes can be expected to maintain their %BF
      and athletes in sports like SW and VB can anticipate an increase in lean mass,
      but the increases may be less than many athletes, coaches, and trainers envision.

PMID- 23860291
TI  - Changes in gait during constant pace treadmill running.
AB  - Treadmills are often used by runners when weather conditions are adverse or a
      specific training effect is desired. Athletes might respond to fatigue
      differently when running on a treadmill compared with overground conditions,
      where pace is typically more variable. The purpose of this study was to measure
      changes in gait parameters over the course of a 10-km treadmill run. Fifteen male
      competitive runners ran at a constant pace for 10 km at 103% of season's best
      time on an instrumented treadmill with in-dwelling force plates, and data were
      analyzed at 5 distances. Kinematic data were derived from high-speed videography
      and results compared between the early and late stages. Before halfway, step
      length increased and cadence decreased, whereas during the latter stages, there
      were significant decreases in impulse and maximum force. Contact time decreased
      and flight time increased continually, but otherwise most gait variables did not
      change. The changes in contact and flight times suggested that athletes altered
      their gait so that more time was spent airborne to allow the treadmill to pass
      under them. In general, however, the runners maintained their techniques
      throughout the run. Constant pace treadmill running might therefore be useful
      with the aim of running for a particular distance and speed with a consistent
      technique unaffected by factors such as gradient or fatigue. However, the
      increase in flight time might have aided the runners because of the nature of
      treadmill running, and athletes and coaches should note that this training effect
      is impractical during overground running.

PMID- 23860292
TI  - Variability of objective and subjective intensities during ball drills in youth
      soccer players.
AB  - The aim of this study was to examine the intrasubject (intraclass coefficient
      correlation [ICC]) and intersubject variability (coefficient of variation [CV])
      of soccer ball drills (BD) involving or not opposition in male youth soccer. For
      this purpose, a collective ball dribbling (DB) exercise and a 7-a-side ball game
      without coach encouragements were considered. Exercise intensity was assessed as
      heart rate (HR), training load (TL), and perceived exertion scales. Fourteen U-14
      male soccer players (age, 14.79 +/- 0.43 years and experience, 6.5 years) of a
      Spanish First Division club academy participated in the study. Ball drills were
      examined for variability over 5 successive training sessions in similar field
      conditions. Results showed that 7-a-side was significantly (p = 0.000) more
      demanding than DB. Indeed the TL, HRmax, HRmean, overall perceived exertion, and
      leg muscular perceived exertion (MPE) resulted 141, 8.7, 11, 56, and 72%, higher
      in 7-a-side than in DB, respectively. In the 7-a-side condition, good
      intersubject (CV < 10%) and low intrasubject (ICC < 0.7) variability were
      observed. In the DB condition, CVs were below 10% CV only for HR variables and
      the ICC values were higher than 0.7 only for MPE. Despite the moderate
      reproducibility of BD not considering opponents, this condition did not reveal to
      induce homogeneous physiological responses in young soccer players. Therefore,
      the use of this kind of drills may be questionable when considered as alternative
      of moderate intensity generic aerobic training. Despite the higher interaction
      between players variability in the opposition drills resulted lower, this
      suggests their use as a specific conditioning exercise.

PMID- 23860293
TI  - The effect of an intervention program on functional movement screen test scores
      in mixed martial arts athletes.
AB  - This study assessed the basic fundamental movements of mixed martial arts (MMA)
      athletes using the functional movement screen (FMS) assessment and determined if
      an intervention program was successful at improving results. Participants were
      placed into 1 of the 2 groups: intervention and control groups. The intervention
      group was required to complete a corrective exercise program 4 times per week,
      and all participants were asked to continue their usual MMA training routine. A
      mid-intervention FMS test was included to examine if successful results were
      noticed sooner than the 8-week period. Results highlighted differences in FMS
      test scores between the control group and intervention group (p = 0.006). Post
      hoc testing revealed a significant increase in the FMS score of the intervention
      group between weeks 0 and 8 (p = 0.00) and weeks 0 and 4 (p = 0.00) and no
      significant increase between weeks 4 and 8 (p = 1.00). A chi analysis revealed
      that the intervention group participants were more likely to have an FMS score
      >14 than participants in the control group at week 4 (chi = 7.29, p < 0.01) and
      week 8 (chi = 5.2, p <= 0.05). Finally, a greater number of participants in the
      intervention group were free from asymmetry at week 4 and week 8 compared with
      the initial test period. The results of the study suggested that a 4-week
      intervention program was sufficient at improving FMS scores. Most if not all, the
      movements covered on the FMS relate to many aspects of MMA training. The
      knowledge that the FMS can identify movement dysfunctions and, furthermore, the
      fact that the issues can be improved through a standardized intervention program
      could be advantageous to MMA coaches, thus, providing the opportunity to adapt
      and implement new additions to training programs.

PMID- 23860294
TI  - Match intensity and pacing strategies in rugby league: an examination of whole
      game and interchanged players, and winning and losing teams.
AB  - There is currently limited information on whether pacing occurs during rugby
      league match play. In addition, to date no research has investigated whether
      pacing strategies differ between winning and losing teams. This study
      investigated the pacing strategies of whole-game and interchanged rugby league
      players. Furthermore, we investigated the pacing strategies of winning and losing
      teams. Fifty-two rugby league players, from a sample of 11 teams competing in a
      semi-elite competition, underwent global positioning system analysis.
      Performances were divided into match quartiles for whole-game and interchanged
      players. Total distance, including low- and high-speed distances, and repeated
      high-intensity effort bouts were recorded. The total distance and low-speed
      distance covered across all quartiles of the match, but specifically quartiles 1
      and 8, were greater for interchanged players than whole-game players. The match
      outcome differentially affected the pacing strategies of whole-game and
      interchanged players. Whole-game players from winning teams set a higher pacing
      strategy than whole-game players from losing teams (effect size [ES] = 1.03 +/-
      0.77, 96%, very likely), whereas interchanged players from losing teams
      demonstrated a greater "end-spurt" than interchanged players from winning teams
      (ES = 0.60 +/- 0.52, 96%, very likely). The pacing strategies of interchanged
      players were higher than whole-game players, irrespective of playing position.
      The results of this study suggest that pacing strategies differ between
      interchanged and whole-game rugby league players. Furthermore, our results
      demonstrate a different pacing strategy between winning and losing teams. These
      findings suggest that physical preparation for rugby league matches, and recovery
      from these matches, should be individualized for whole-game and interchanged
      players. Finally, performing physically intense training on a regular basis is
      likely to develop the physical and mental qualities required to regularly compete
      at higher playing intensities.

PMID- 23860295
TI  - Effects of bronchodilators on regional lung sound distribution in patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Bronchodilators have been reported to influence regional lung
      ventilation in patients with chronic obstructive pulmonary disease (COPD), which
      may change regional lung sound distribution. Vibration response imaging (VRI) is
      a lung imaging system for the assessment of breath sounds. OBJECTIVE: To evaluate
      the effects of a short-acting beta2-agonist (SABA) on the regional distribution
      of lung sounds in COPD patients. METHODS: A double-blind crossover trial was
      performed to compare the treatment of COPD patients with an SABA (20 ug of
      inhaled procaterol) versus a placebo. The percentage of regional lung sound
      energy [quantitative lung data (QLD)] was evaluated with VRI. VRI, spirometry,
      and impulse oscillometry (IOS) were performed immediately before and 30 min after
      SABA administration. RESULTS: Ten male patients (69.6 +/- 14.2 years of age,
      percentage predicted forced expiratory volume in 1 s: 43.8 +/- 16.9%) were
      evaluated. The use of an SABA produced significant functional improvements in the
      spirometric and IOS measurements. Among the homogeneous emphysema patients (n =
      7), the upper-lung QLD decreased (from 24.2 +/- 5.8 to 18.8 +/- 6.1%, p < 0.05)
      and the lower-lung QLD increased (from 37.9 +/- 12.7 to 46.1 +/- 14.3%, p < 0.05)
      following SABA inhalation. However, the significant redistribution of the
      regional lung QLD to the lower-lung field was not observed in 2 of the 3
      inhomogeneous emphysema patients. CONCLUSION: The additional use of an SABA by
      COPD patients improved their pulmonary function, which was accompanied by changes
      in regional lung air flow. The distribution of emphysematous lesions and the
      bronchial reactivity to SABA appeared to affect the redistribution of the lung
      sounds following bronchodilator administration.

PMID- 23860296
TI  - Cerebellar atrophy in childhood arterial ischemic stroke: acute diffusion MRI
      biomarkers.
AB  - BACKGROUND AND PURPOSE: Crossed cerebellar atrophy is uncommon in childhood
      arterial ischemic stroke. Acute corticospinal tract diffusion-weighted imaging
      (CST-DWI) changes occur in stroke of all ages. Contralateral CST-DWI is
      unexplained but approximates corticopontocerebellar pathways. We hypothesized
      that cerebellar atrophy can be quantified on clinical neuroimaging in childhood
      arterial ischemic stroke and is predicted by contralesional CST-DWI. METHODS:
      Consecutive children (>28 days-18 years) were included with the following
      features: (1) acute, unilateral, middle cerebral artery arterial ischemic stroke,
      (2) DWI <14 days from stroke onset, (3) anatomic T1 MRI >6 months, and (4)
      Pediatric Stroke Outcome Measure >12 months. Blinded scorers measured cerebellar
      volumes (left/right/hemisphere/vermis/total) using Osirix software. Cerebellar
      volumes ratios (nonstroke/stroke) were expressed as asymmetry indices (AI), with
      chronic/acute ratio <1.0 suggesting crossed atrophy. Acute brain stem and
      cerebellum (peduncle, hemisphere) DWI ratios were scored. Software measures were
      compared with visual inspection. Associations between AI, motor outcome
      (good/poor), and contralesional CST-DWI were sought. Rater reliabilities were
      assessed. RESULTS: Twenty-three children were studied (median age, 6.3+/-4.4
      years; 62% male). Baseline cerebellar volumes were comparable (right=56.9 cm(3),
      left=57.1 cm(3)). Cerebellar atrophy was suggested across the sample with overall
      AI <1.0 (0.973+/-0.05; P=0.009). Visual atrophy detection was specific (~100%)
      but insensitive (54%). Children with poor motor outcome did not have lower AI
      (0.983+/-0.027 versus 0.965+/-0.068; P=0.40); however, children with acute
      contralesional CST-DWI did (0.928+/-0.078 versus 986+/-0.040; P=0.03). Acute
      cerebellar DWI did not predict atrophy. Rater reliabilities were excellent
      (>0.92). CONCLUSIONS: Cerebellar atrophy can be demonstrated on MRI in childhood
      arterial ischemic stroke. Association with acute contralesional pontine DWI
      signal suggests early degeneration of corticopontocerebellar connections. The
      clinical significance of cerebellar atrophy in childhood stroke remains to be
      determined.

PMID- 23860297
TI  - Letter by Gaillard et al regarding article, "Thrombolysis despite recent stroke:
      a case series".

PMID- 23860299
TI  - Response to letter by Gaillard et al regarding article, "Thrombolysis despite
      recent stroke: a case series".

PMID- 23860300
TI  - Overlap of diseases underlying ischemic stroke: the ASCOD phenotyping.
AB  - BACKGROUND AND PURPOSE: ASCOD phenotyping (A, atherosclerosis; S, small vessel
      disease; C, cardiac pathology; O, other causes; and D, dissection) assigns a
      degree of likelihood to every potential cause (1 for potentially causal, 2 for
      causality is uncertain, 3 for unlikely causal but disease is present, 0 for
      absence of disease, and 9 for insufficient workup to rule out the disease)
      commonly encountered in ischemic stroke. We used ASCOD to investigate the overlap
      of underlying vascular diseases and their prognostic implication. METHODS: A
      single rater applied ASCOD in 405 patients enrolled in the Asymptomatic
      Myocardial Ischemia in Stroke and Atherosclerotic Disease study. RESULTS: A was
      present in 90% of patients (A1=43% and A2=15%), C in 52% (C1=23% and C2=14%), and
      S in 66% (S1=11% and S2=2%). On the basis of grades 1 and 2, 25% of patients had
      multiple underlying diseases, and 80% when all 3 grades were considered. The main
      overlap was found between A and C; among C1 patients, A was present in 92% of
      cases (A1=28%, A2=20%, and A3=44%). Conversely, among A1 patients, C was present
      in 47% of cases (C1=15%, C2=15%, and C3=17%). Grades for C were associated with
      gradual increase in the 3-year risk of vascular events, whereas risks were
      similar across A grades, meaning that the mere presence of atherosclerotic
      disease qualifies for high risk, regardless the degree of likelihood for A.
      CONCLUSIONS: ASCOD phenotyping shows that the large overlap among the 3 main
      diseases, and the high prevalence of any form of atherosclerotic disease,
      reinforces the need to systematically control atherosclerotic risk factors in all
      ischemic strokes.

PMID- 23860301
TI  - New oral anticoagulants: great promise for therapeutic advance but great
      knowledge gaps remain to be filled.

PMID- 23860298
TI  - Acute Stroke Imaging Research Roadmap II.

PMID- 23860302
TI  - The role of metacognition in prospective memory: anticipated task demands
      influence attention allocation strategies.
AB  - The present study investigates how individuals distribute their attentional
      resources between a prospective memory task and an ongoing task. Therefore,
      metacognitive expectations about the attentional demands of the prospective
      memory task were manipulated while the factual demands were held constant. In
      Experiments 1a and 1b, we found attentional costs from a prospective-memory task
      with low factual demands to be significantly reduced when information about the
      low to-be-expected demands were provided, while prospective-memory performance
      remained largely unaffected. In Experiment 2, attentional monitoring in a more
      demanding prospective-memory task also varied with information about the to-be
      expected demands (high vs. low) and again there were no equivalent changes in
      prospective-memory performance. These findings suggest that attention-allocation
      strategies of prospective memory rely on metacognitive expectations about
      prospective-memory task demands. Furthermore, the results suggest that
      attentional monitoring is only functional for prospective memory to the extent to
      which anticipated task demands reflect objective task demands. 

PMID- 23860303
TI  - Synesthetic grapheme-color percepts exist for newly encountered Hebrew,
      Devanagari, Armenian and Cyrillic graphemes.
AB  - Grapheme-color synesthetes experience color, not physically present, when viewing
      symbols. Synesthetes cannot remember learning these associations. Must
      synesthetic percepts be formed during a sensitive period? Can they form later and
      be consistent? What determines their nature? We tested grapheme-color synesthete,
      MC2, before, during and after she studied Hindi abroad. We investigated whether
      novel graphemes elicited synesthetic percepts, changed with familiarity, and/or
      benefited from phonemic information. MC2 reported color percepts to novel
      Devanagari and Hebrew graphemes. MC2 monitored these percepts over 6months in a
      Hindi-speaking environment. MC2 and synesthete DN, reported synesthetic percepts
      for Armenian graphemes, or Cyrillic graphemes+phonemes over time. Synesthetes,
      not controls, reported color percepts for novel graphemes that gained consistency
      over time. Phonemic information did not enhance consistency. Thus, synesthetes
      can form and consolidate percepts to novel graphemes as adults. These percepts
      may depend on pre-existing grapheme-color relationships but they can flexibly
      shift with familiarity. 

PMID- 23860304
TI  - Transient charge and energy balance in graphene induced by ultrafast
      photoexcitation.
AB  - Ultrafast optical pump-probe spectroscopy measurements on monolayer graphene
      reveal significant optical nonlinearities. We show that strongly photoexcited
      graphene monolayers with 35 fs pulses quasi-instantaneously build up a broadband,
      inverted Dirac-fermion population. Optical gain emerges and directly manifests
      itself via a negative conductivity at the near-infrared region for the first 200
      fs, where stimulated emission completely compensates for absorption loss in the
      graphene layer. To quantitatively investigate this transient, extremely dense
      photoexcited Dirac-fermion state, we construct a two-chemical-potential model, in
      addition to a time-dependent transient carrier temperature above the lattice
      temperature, to describe the population inverted electronic state metastable on
      the time scale of tens of femtoseconds generated by a strong exciting pulse. The
      calculated transient optical conductivity reveals a complete bleaching of
      absorption, which sets the saturation density during the pulse propagation. In
      particular, the model calculation reproduces the negative optical conductivity at
      lower frequencies in the states close to saturation, corroborating the observed
      femtosecond stimulated emission and optical gain in the wide near-infrared
      window.

PMID- 23860306
TI  - Vemurafenib-induced eccrine squamous syringometaplasia.
AB  - We report herein a patient treated with vemurafenib for a stage IV melanoma who
      developed an eruption related to eccrine squamous syringometaplasia (ESS). This
      entity is a well-described side effect of cytostatic therapies used for malignant
      neoplasia and is clinically characterized by a symmetric cutaneous eruption
      composed of papules and vesicles preferentially located on fold and
      intertriginous areas. It is histologically defined by a squamous metaplasia of
      eccrine ductal epithelium. ESS represents another skin eruption to be added to
      the list of cutaneous adverse events associated with vemurafenib, a selective
      BRAF inhibitor used to treat patients with metastatic melanoma harboring the
      V600E mutation. The discussion focuses on the pathogenesis of ESS secondary to
      vemurafenib and on alternative diagnoses.

PMID- 23860305
TI  - Building a better analgesic: multifunctional compounds that address injury
      induced pathology to enhance analgesic efficacy while eliminating unwanted side
      effects.
AB  - The most highly abused prescription drugs are opioids used for the treatment of
      pain. Physician-reported drug-seeking behavior has resulted in a significant
      health concern among doctors trying to adequately treat pain while limiting the
      misuse or diversion of pain medications. In addition to abuse liability, opioid
      use is associated with unwanted side effects that complicate pain management,
      including opioid-induced emesis and constipation. This has resulted in
      restricting long-term doses of opioids and inadequate treatment of both acute and
      chronic debilitating pain, demonstrating a compelling need for novel analgesics.
      Recent reports indicate that adaptations in endogenous substance P/neurokinin-1
      receptor (NK1) are induced by chronic pain and sustained opioid exposure, and
      these changes may contribute to processes responsible for opioid abuse liability,
      emesis, and analgesic tolerance. Here, we describe a multifunctional mu-/delta
      opioid agonist/NK1 antagonist compound [Tyr-d-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH
      Bn(CF3)2 (TY027)] that has a preclinical profile of excellent antinociceptive
      efficacy, low abuse liability, and no opioid-related emesis or constipation. In
      rodent models of acute and neuropathic pain, TY027 demonstrates analgesic
      efficacy following central or systemic administration with a plasma half-life of
      more than 4 hours and central nervous system penetration. These data demonstrate
      that an innovative opioid designed to contest the pathology created by chronic
      pain and sustained opioids results in antinociceptive efficacy in rodent models,
      with significantly fewer side effects than morphine. Such rationally designed,
      multitargeted compounds are a promising therapeutic approach in treating patients
      who suffer from acute and chronic pain. 

PMID- 23860307
TI  - Simultaneous modified Camitz opponensplasty using a pulley at the radial side of
      the flexor retinaculum in severe carpal tunnel syndrome.
AB  - Camitz opponensplasty using the palmaris longus has been used in patients
      undergoing open carpal tunnel release. It is considered to have several
      advantages over other opponensplasty techniques, but it provides weak flexion and
      pronation, which are prerequisites for opposition. To address this shortcoming,
      we have used a modified Camitz procedure with a pulley at the radial side of the
      dissected flexor retinaculum and have assessed the results in comparison with the
      conventional Camitz procedure. Both procedures provided significant improvements
      in palmar abduction and Disabilities of the Arm, Shoulder, and Hand and Kapandji
      scores at 3 months post-operatively, but patients who underwent the modified
      Camitz procedure showed better improvement in pulp pinch, palmar abduction, and
      thumb pronation. 

PMID- 23860308
TI  - Karl Jaspers' multiperspectivalism.
AB  - In later editions of his General Psychopathology, Karl Jaspers prescribes many
      different methods and theoretical points of view for psychopathologists to
      utilize. Each of these perspectives on the subject matter of psychopathology,
      however, gives the investigator access to only one dimension of the patient's
      being. Hence, Jaspers insists that several different perspectives must be
      employed in order to avoid a one-sided and partial comprehension of the patient
      and his or her problem. He advocates a multiperspectival approach in
      psychopathology. Nevertheless, Jaspers remains aware that the patient is a
      unified whole. This unified whole, however, is not knowable as such, but can
      rather be approached only under the guidance of an 'idea' of the whole. Jaspers
      takes the basic notion of 'idea' (Idee) from Kant, but he modifies and uses it
      for his own purposes. Jaspers' multiperspectivalism may seem to invite charges of
      relativism because it leaves the psychopathologist to 'pick and choose' any
      method or theory he or she prefers. This charge is addressed by admitting that
      there does exist a certain relativism in Jaspers' position in that any one
      perspective does provide only one approach to the reality of the patient and that
      other equally useful perspectives could have been chosen. However, each
      perspective itself can be subjected to test by evidence, and in such tests,
      claims made from that perspective can be found to be true or false. Helen
      Longino's theory of scientific knowledge helps support such a thesis.

PMID- 23860309
TI  - Medical errors in laboratory medicine: pathways to improvement.

PMID- 23860310
TI  - Newborn screening and diagnosis of mucopolysaccharidoses.
AB  - Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme
      activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched
      polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin
      sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS),
      and hyaluronan. Their catabolism may be blocked singly or in combination
      depending on the specific enzyme deficiency. There are 11 known enzyme
      deficiencies, resulting in seven distinct forms of MPS with a collective
      incidence of higher than 1 in 25,000 live births. Accumulation of undegraded
      metabolites in lysosomes gives rise to distinct clinical syndromes. Generally,
      the clinical conditions progress if untreated, leading to developmental delay,
      systemic skeletal deformities, and early death. MPS disorders are potentially
      treatable with enzyme replacement therapy or hematopoietic stem cell
      transplantation. For maximum benefit of available therapies, early detection and
      intervention are critical. We recently developed a novel high-throughput
      multiplex method to assay DS, HS, and KS simultaneously in blood samples by using
      high performance liquid chromatography/tandem mass spectrometry for MPS. The
      overall performance metrics of HS and DS values on MPS I, II, and VII patients
      vs. healthy controls at newborns were as follows using a given set of cut-off
      values: sensitivity, 100%; specificity, 98.5-99.4%; positive predictive value,
      54.5-75%; false positive rate, 0.62-1.54%; and false negative rate, 0%. These
      findings show that the combined measurements of these three GAGs are sensitive
      and specific for detecting all types of MPS with acceptable false
      negative/positive rates. In addition, this method will also be used for
      monitoring therapeutic efficacy. We review the history of GAG assay and
      application to diagnosis for MPS. 

PMID- 23860313
TI  - Learning and memory: locating lost memories.

PMID- 23860311
TI  - The effect of neonatal gene therapy with a gamma retroviral vector on cardiac
      valve disease in mucopolysaccharidosis VII dogs after a decade.
AB  - Mucopolysaccharidosis VII (MPS VII) is due to deficient activity of the lysosomal
      enzyme beta-glucuronidase (GUSB) and results in the accumulation of
      glycosaminoglycans (GAGs). This study determined the long-term effect of neonatal
      intravenous injection of a gamma retroviral vector (RV) on cardiac valve disease
      in MPS VII dogs. Transduced hepatocytes secreted GUSB into the blood for up to 11
      years at levels similar to or greater than those achieved with enzyme replacement
      therapy (ERT). Valve regurgitation and thickening were scored from 0 (normal) to
      +4 (severely abnormal). At 1 year, untreated MPS VII dogs had mitral
      regurgitation, mitral valve thickening, aortic regurgitation, and aortic valve
      thickening scores of 2.3 +/- 0.7, 2.3 +/- 0.6, 1.8 +/- 0.5, and 1.6 +/- 0.7,
      respectively, which were higher than the values of 0.6 +/- 0.1, 0.1 +/- 0.4, 0.3
      +/- 0.8, and 0.1 +/- 0.4, respectively, in treated MPS VII dogs. Treated MPS VII
      dogs maintained low aortic regurgitation and aortic valve thickening scores in
      their lifetime. Although mitral regurgitation and mitral valve thickening scores
      increased to 2.0 at >= 8 years of age in the treated MPS VII dogs, older normal
      dogs from the colony had similar scores, making it difficult to assess mitral
      valve disease. Older treated dogs had calcification within the mitral and the
      aortic valve annulus, while GUSB staining demonstrated enzyme activity within the
      mitral valve. We conclude that neonatal RV-mediated gene therapy reduced cardiac
      valve disease in MPS VII dogs for up to 11 years, and propose that neonatal
      initiation of ERT should have a similar effect.

PMID- 23860312
TI  - Hypnotic suggestion: opportunities for cognitive neuroscience.
AB  - Hypnosis uses the powerful effects of attention and suggestion to produce, modify
      and enhance a broad range of subjectively compelling experiences and behaviours.
      For more than a century, hypnotic suggestion has been used successfully as an
      adjunctive procedure to treat a wide range of clinical conditions. More recently,
      hypnosis has attracted a growing interest from a cognitive neuroscience
      perspective. Recent studies using hypnotic suggestion show how manipulating
      subjective awareness in the laboratory can provide insights into brain mechanisms
      involved in attention, motor control, pain perception, beliefs and volition.
      Moreover, they indicate that hypnotic suggestion can create informative analogues
      of clinical conditions that may be useful for understanding these conditions and
      their treatments.

PMID- 23860314
TI  - Attention: fine-tuning the synaptic signal.

PMID- 23860315
TI  - Cytologic features during intraoperative assessment of central neurocytoma: a
      report of three cases and review of the literature.
AB  - BACKGROUND: Central neurocytomas (CNs) are infrequent intraventricular tumors
      with features of neuronal differentiation that affect young adults and have an
      excellent prognosis after total resection. The main differential intraoperative
      diagnoses are oligodendrogliomas, ependymomas and non-Hodgkin's lymphomas;
      therefore, an accurate and precise intraoperative diagnosis is essential, making
      the cytologic features the hallmark for cytopathologists, surgical pathologists
      and neurosurgeons alike. Seven previous reports have described 18 cases of CNs
      and have addressed the cytodiagnostic criteria during intraoperative assessment
      in the English medical literature. CASES: Three patients (23 years old/male, 29
      years old/female and 28 years old/male) were evaluated during intraoperative
      assessment as CNs. They showed intraventricular tumors that measured 6.5, 3.5 and
      6.6 cm, respectively. The cytologic features common in these cases were: (1)
      monotonous or isomorphic round cells, (2) small nuclei with stippled or granular
      chromatin, and (3) acellular fibrillary areas or neuropil (islands). Other
      cytologic features often encountered were: rosette-like structures,
      micronucleoli, perinuclear haloes, well-formed capillary-sized vessels and
      calcifications. CONCLUSION: Differential diagnosis of CNs can be a diagnostic
      challenge. The integration of radiologic imaging and touch preparations taking
      into account specific cytologic features and frozen sections is necessary for an
      optimal intraoperative assessment.

PMID- 23860316
TI  - Ultra-precision measurement and control of angle motion in piezo-based platforms
      using strain gauge sensors and a robust composite controller.
AB  - The measurement and control strategy of a piezo-based platform by using strain
      gauge sensors (SGS) and a robust composite controller is investigated in this
      paper. First, the experimental setup is constructed by using a piezo-based
      platform, SGS sensors, an AD5435 platform and two voltage amplifiers. Then, the
      measurement strategy to measure the tip/tilt angles accurately in the order of
      sub-MUrad is presented. A comprehensive composite control strategy design to
      enhance the tracking accuracy with a novel driving principle is also proposed.
      Finally, an experiment is presented to validate the measurement and control
      strategy. The experimental results demonstrate that the proposed measurement and
      control strategy provides accurate angle motion with a root mean square (RMS)
      error of 0.21 MUrad, which is approximately equal to the noise level. 

PMID- 23860317
TI  - An integrative structural health monitoring system for the local/global responses
      of a large-scale irregular building under construction.
AB  - In this study, a practical and integrative SHM system was developed and applied
      to a large-scale irregular building under construction, where many challenging
      issues exist. In the proposed sensor network, customized energy-efficient
      wireless sensing units (sensor nodes, repeater nodes, and master nodes) were
      employed and comprehensive communications from the sensor node to the remote
      monitoring server were conducted through wireless communications. The long-term
      (13-month) monitoring results recorded from a large number of sensors (75
      vibrating wire strain gauges, 10 inclinometers, and three laser displacement
      sensors) indicated that the construction event exhibiting the largest influence
      on structural behavior was the removal of bents that were temporarily installed
      to support the free end of the cantilevered members during their construction.
      The safety of each member could be confirmed based on the quantitative evaluation
      of each response. Furthermore, it was also confirmed that the relation between
      these responses (i.e., deflection, strain, and inclination) can provide
      information about the global behavior of structures induced from specific events.
      Analysis of the measurement results demonstrates the proposed sensor network
      system is capable of automatic and real-time monitoring and can be applied and
      utilized for both the safety evaluation and precise implementation of buildings
      under construction. 

PMID- 23860318
TI  - A distal estrogen responsive element upstream the cap site of human transthyretin
      gene is an enhancer-like element upon ERalpha and/or ERbeta transactivation.
AB  - Previous studies reported that 17 beta-estradiol (E2) is responsible for the up
      regulation of transthyretin (TTR) expression via an estrogen receptor (ER)
      dependent pathway in rat choroid plexus (CP) and liver. A computer-assisted
      homology search identified a putative estrogen-responsive element (ERE) in the 5'
      flanking region of the human TTR (hTTR) gene (ERETTR), with the sequence
      aAGTCAAAGTGACCa, between -3406 and -3392 bp. Luciferase reporter assays and
      electrophoretic mobility shift (EMSA) and supershift analysis were carried out to
      investigate if E2 regulates TTR transcription via this putative ERE. Luciferase
      reporter assays in COS-7 cells were carried out with a plasmid construction where
      the TTR fragment containing the putative ERETTR was cloned in pGL2-promoter
      vector (pGL2-P) (pGL2-P/TTR), co-transfected with estrogen receptor alpha
      (ERalpha) and/or estrogen receptor beta (ERbeta) expression vectors. These assays
      demonstrated that, upon incubation with E2, one or both ERs (alpha and/or beta)
      transactivate the reporter gene. The pGL2-P/TTR showed a significant
      transactivation of up to 6.8-fold, by E2, when co-transfected with ERbeta, and up
      to 4-fold with ERalpha. Specific binding of ER (alpha and/or beta) to ERETTR was
      demonstrated by EMSA and supershift assays confirmed the binding to ERalpha
      and/or ERbeta. Our findings further suggest a mechanism underlying the regulation
      of TTR expression through the identification of a novel ERE in the TTR gene,
      which functions as an E2-dependent enhancer-like element.

PMID- 23860319
TI  - Molecular regulation of santalol biosynthesis in Santalum album L.
AB  - Santalum album L. commonly known as East-Indian sandal or chandan is a
      hemiparasitic tree of family santalaceae. Santalol is a bioprospecting molecule
      present in sandalwood and any effort towards metabolic engineering of this
      important moiety would require knowledge on gene regulation. Santalol is a
      sesquiterpene synthesized through mevalonate or non-mevalonate pathways. First
      step of santalol biosynthesis involves head to tail condensation of isopentenyl
      pyrophosphate (IPP) with its allylic co-substrate dimethyl allyl pyrophosphate
      (DMAPP) to produce geranyl pyrophosphate (GPP; C10 - a monoterpene). GPP upon one
      additional condensation with IPP produces farnesyl pyrophosphate (FPP; C15 - an
      open chain sesquiterpene). Both the reactions are catalyzed by farnesyl
      diphosphate synthase (FDS). Santalene synthase (SS), a terpene cyclase catalyzes
      cyclization of open ring FPP into a mixture of cyclic sesquiterpenes such as
      alpha-santalene, epi-beta-santalene, beta-santalene and exo bergamotene, the main
      constituents of sandal oil. The objective of the present work was to generate a
      comprehensive knowledge on the genes involved in santalol production and study
      their molecular regulation. To achieve this, sequences encoding farnesyl
      diphosphate synthase and santalene synthase were isolated from sandalwood using
      suppression subtraction hybridization and 2D gel electrophoresis technology.
      Functional characterization of both the genes was done through enzyme assays and
      tissue-specific expression of both the genes was studied. To our knowledge, this
      is the first report on studies on molecular regulation, and tissue-specific
      expression of the genes involved in santalol biosynthesis.

PMID- 23860321
TI  - A potentially functional polymorphism in the regulatory region of let-7a-2 is
      associated with an increased risk for diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is a major diabetic complication. However, the
      initiating molecular events triggering DN are unknown. MicroRNAs (miRNAs) have
      recently been identified as regulators that modulate the target gene expression
      and are involved in DN. However, the evidence of the mechanism is still
      insufficient in human samples. In this study, microRNA microarray assay was used
      to study gene differential expression profiles in DN and diabetes mellitus (DM)
      patients. One of the specific differentially expressed microRNAs, let-7a, was
      down-expressed in DN. Additionally, the expression of let-7a was also decreased
      in DN by real-time RT PCR in the patients' samples. Moreover, single nucleotide
      polymorphism (SNP) analysis was used to evaluate the relationship between three
      SNPs in the regulatory region of let-7a-2 gene and the risk of DN in the Chinese
      Han population by means of PCR-restriction fragment length polymorphism (RFLP
      PCR). Also, the genotype and allele frequencies of let-7a-2 polymorphism were
      tested in 274 individuals, including 108 DN, 104 DM patients and 62 health
      control individuals (CON). It was found that a variant rs1143770 and the
      distributions of CT/TT genotypes were significantly different in three groups,
      and the CT+TT genotypes frequencies were significantly higher in DN and DM groups
      than that in CON group. In conclusion, let-7a-2 might participate in the
      regulation of the occurrence of DN, and a potential variant rs1143770 was
      significantly associated with the increased risk for DN.

PMID- 23860320
TI  - Resistin disrupts glycogen synthesis under high insulin and high glucose levels
      by down-regulating the hepatic levels of GSK3beta.
AB  - The effect of mouse resistin on hepatic insulin resistance in vivo and in vitro,
      and its possible molecular mechanism were examined. Focusing on liver glycogen
      metabolism and gluconeogenesis, which are important parts of glucose metabolism,
      in primary cultures of rat hepatocytes we found that glycogen content was
      significantly lower (P<0.05) after treatment with recombinant murine resistin
      only in the presence of insulin plus glucose stimulation. Protein levels of
      factors in the insulin signaling pathway involved in glycogen synthesis were
      examined by Western blot analysis, with the only significant change observed
      being the level of phosphorylated (at Ser 9) glycogen synthase kinase-3beta (GSK
      3beta) (P<0.001). No differences in the protein levels for the insulin receptor
      beta (IRbeta), insulin receptor substrates (IRS1 and IRS2), phosphatidylinositol
      3-kinase (PI3K), protein kinase B (Akt) or their phosphorylated forms were
      observed between control and resistin treated primary rat hepatocytes. In a mouse
      model with high liver-specific expression of resistin, fasting blood glucose
      levels and liver glycogen content changed. Fasting blood glucose levels were
      significantly higher (P<0.001) in the model mice, compared to the control mice,
      while the glycogen content of the liver tissue was about 60% of that of the
      control mice (P<0.05). The gluconeogenic response was not altered between the
      experimental and control mice. The level of phosphorylated GSK-3beta in the liver
      tissue was also decreased (P<0.05) in the model mice, consistent with the results
      from the primary rat hepatocytes. Our results suggest that resistin reduces the
      levels of GSK-3beta phosphorylated at Ser 9 leading to impaired hepatic insulin
      action in primary rat hepatocytes and in a mouse model with high liver-specific
      expression of resistin.

PMID- 23860322
TI  - Polymorphisms in STK17A gene are associated with systemic lupus erythematosus and
      its clinical manifestations.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disorder with several
      clinical manifestations. SLE etiology has a strong genetic component, which plays
      a key role in disease's predisposition, as well as participation of environmental
      factors, such and UV light exposure. In this regard, we investigated whether
      polymorphisms in STK17A, a DNA repair related gene, encoding for serine/threonine
      protein kinase 17A, are associated with SLE susceptibility. A total of 143 SLE
      patients and 177 healthy controls from Southern Brazil were genotyped for five
      STK17A TagSNPs. Our results indicated association of rs7805969 SNP (A and G/A
      genotype, OR=1.40 and OR=1.73, respectively) with SLE predisposition and the
      following clinical manifestations: arthritis, cutaneous and immunological
      alterations. When analyzing haplotypes distribution, we found association between
      TGGTC, TAGTC and AAGAT haplotypes and risk to develop SLE. When considering
      clinical manifestations, the haplotypes TGGTT and TAGTC were associated with
      protection against cutaneous alterations and the haplotype TAGTC to hematological
      alterations. We also observed association between SLE clinical manifestations and
      ethnicity, with the European-derived patients being more susceptible to cutaneous
      and hematological alterations. 

PMID- 23860323
TI  - Regulation of fibrillin-1 gene expression by Sp1.
AB  - Mutations in the fibrillin-1 gene (FBN1) cause Marfan Syndrome (MFS), a
      hereditary disorder of connective tissue. The transcription of FBN1 has been
      reported to be driven by a short ultraconserved region (SUPR) in the 5'
      untranslated exon A of FBN1, but the nature of other factors involved in FBN1
      gene regulation has not been clarified. In this study, we characterized the
      transcription factors involved in FBN1 gene regulation. The results show that Sp1
      protein binds to two putative binding sites in the promoter of FBN1.
      Overexpression of Sp1 resulted in a significant increase in both promoter
      activity and FBN1 mRNA level in HEK 293 cells, whereas inhibition or knockdown of
      Sp1 decreased FBN1 gene expression. In addition, we found that Poly [ADP-ribose]
      polymerase 1 (PARP1) binds to the palindromic sequence TCTCGCGAGA in the
      ultraconserved region of the FBN1 promoter and that the regulation of FBN1
      expression by PARP1 is dependent on Sp1. These results indicate that both Sp1 and
      PARP1 contribute to FBN1 gene expression. These observations add to our
      understanding of the transcriptional regulation of FBN1 gene expression.

PMID- 23860324
TI  - Regulation of cell proliferation and migration in gallbladder cancer by zinc
      finger X-chromosomal protein.
AB  - Gallbladder carcinoma (GBC) is one of the mostly aggressive and fatal
      malignancies. However, little is known about the oncogenic genes that contributed
      to the development of GBC. Zinc finger X-chromosomal protein (ZFX) was a novel
      member of the Krueppel C2H2-type zinc-finger protein family and its down
      regulation led to impaired cell growth in human laryngeal squamous cell
      carcinoma. Here, we aim to investigate the function of ZFX in GBC cell
      proliferation and migration. Loss of function analysis was performed on GBC cell
      line (GBC-SD) using lentivirus-mediated siRNA against ZFX. The proliferation, in
      vitro tumorigenesis (colony-formation) ability as well as cell migration was
      significantly suppressed after GBC-SD cells which were infected with ZFX-siRNA
      expressing lentivirus (Lv-shZFX). Our finding suggested that ZFX promoted the
      growth and migration of GBC cells and could present a potential molecular target
      for gene therapy of GBC.

PMID- 23860325
TI  - Polymorphisms in FTO and near TMEM18 associate with type 2 diabetes and
      predispose to younger age at diagnosis of diabetes.
AB  - Variations in the FTO gene and near the TMEM18 gene are risk factors for common
      form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim
      was to investigate the contribution of these variants to risk of T2D in a
      population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and
      fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987
      patients with T2D and 1080 controls selected from the Latvian Genome Data Base
      (LGDB). We confirmed association of SNPs in the first intron (rs11642015,
      rs62048402 and rs9939609) of FTO and rs7561317 representing the TMEM18 locus with
      T2D. Association between SNP in FTO and T2D remained significant after correction
      for body mass index (BMI). The rs57103849 located in the fourth intron of FTO and
      rs7561317 in TMEM18 showed BMI independent association with younger age at
      diagnosis of T2D. Our results add to the evidence that BMI related variants in
      and near FTO and TMEM18 may increase the risk for T2D not only through secondary
      effects of obesity. The influence of variants in the fourth intron of the FTO
      gene on development of T2D may be mediated by mechanisms other than those
      manifested by SNPs in the first intron of the same gene.

PMID- 23860326
TI  - Genes alternations with exposure time of environmental factors.
AB  - A theoretical model discussing the environmental factors (EFs) effect of exposure
      time on genes, which leads to human diseases, is presented using multi-logistic
      model. The advantages and limitations of this model are discussed in terms of its
      usefulness for simulating genetic samples. It has been shown that EFs affect
      genes with the same degree both at high exposure level, low exposure time and at
      low exposure level, high exposure time. 

PMID- 23860327
TI  - Effect of genetic variations within the SH2B2 gene on the growth of Chinese
      cattle.
AB  - As an adaptor protein, apart from potentiating Janus kinase 2 (JAK2) activation
      and promoting the insulin signaling pathway, Src homology 2 B 2 (SH2B2)
      indirectly takes part in the regulation of glucose uptake through the c
      Cb1/CAP/TC10 pathway, which can in turn affect growth. In this study, we
      identified a 4bp indel mutation and three single nucleotide polymorphisms (SNPs)
      within the SH2B2 gene in 959 individuals from five Chinese cattle breeds by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and
      sequencing. Based on the four variations, 12 haplotypes were identified.
      Additionally, there was a tendency that in every population pair-wise linkages
      increased progressively from V1-V2 to V3-V4. By association analysis, positive
      effects of genotypes CC and CT (snp1220 locus), DI (4bp indel locus), and CC
      (snp21049 locus) on growth traits were obtained. Furthermore, when combined,
      individuals with the combination CCDITTCC showed the best performance at an early
      age. These results were suggestive of an association of snp1220, 4bp indel and
      snp12049 with growth performance in Nanyang cattle, indicating possibly the
      candidate role of the SH2B2 gene in marker assisted selection in a beef cattle
      breeding program.

PMID- 23860328
TI  - In vitro self-assembly of human pericyte-supported endothelial microvessels in
      three-dimensional coculture: a simple model for interrogating endothelial
      pericyte interactions.
AB  - We describe a method for coculture of macro- or microvascular human endothelial
      cells (ECs) and pericytes (PCs) within a 3-dimensional (3-D) protein matrix
      resulting in lumenized EC cords invested by PCs. To prevent apoptotic cell death
      of ECs in 3-D culture, human umbilical vein or dermal microvascular ECs were
      transduced to express the antiapoptotic protein Bcl-2. To prevent PC-mediated gel
      contraction, the collagen-fibronectin gel was polymerized within a polyglycolic
      acid nonwoven matrix. Over the first 24-48 h, EC-only gels spontaneously formed
      cords that developed lumens via vacuolization; such vascular networks were
      maintained for up to 7 days. In EC-PC cocultures, PCs were recruited to the EC
      networks. PC investment of EC cords both limited the lumen diameter and increased
      the degree of vascular network arborization. Peg and socket junctions formed
      between ECs and PCs in this system, but dye transfer, indicative of gap junction
      formation, was not observed. This simple system can be used to analyze
      bidirectional signals between ECs and PCs in a 3-D geometry.

PMID- 23860329
TI  - CB1 agonists, locally applied to the cortico-thalamic circuit of rats with
      genetic absence epilepsy, reduce epileptic manifestations.
AB  - Drugs that modulate the endocannabinoid system and endocannabinoids typically
      play an anticonvulsant role although some proconvulsant effects have been
      reported both in humans and animal models. Moreover, no evidence for a role of
      the cannabinoid system in human absence epilepsy has been found although limited
      evidence of efficacy in relevant experimental animal models has been documented.
      This study aims to characterize the role of cannabinoids in specific areas of the
      cortico-thalamic network involved in oscillations that underlie seizures in a
      genetic animal model of absence epilepsy, the WAG/Rij rat. We assessed the
      effects of focal injection of the endogenous cannabinoid, anandamide (AEA), a non
      selective CB receptor agonist (WIN55,212) and a selective CB1 receptor
      antagonist/inverse agonist (SR141716A) into thalamic nuclei and primary
      somatosensory cortex (S1po) of the cortico-thalamic network. AEA and WIN both
      reduced absence seizures independently from the brain focal site of infusion
      while, conversely, rimonabant increased absence seizures but only when focally
      administered to the ventroposteromedial thalamic nucleus (VPM). These results,
      together with previous reports, support therapeutic potential for endocannabinoid
      system modulators in absence epilepsy and highlight that attenuated
      endocannabinergic function may contribute to the generation and maintenance of
      seizures. Furthermore, the entire cortico-thalamic network responds to
      cannabinoid treatment, indicating that in all areas considered, CB receptor
      activation inhibits the pathological synchronization that subserves absence
      seizures. In conclusion, our result might be useful for the identification of
      future drug therapies in absence epilepsy.

PMID- 23860330
TI  - Metoprolol-mediated amelioration of sympathetic nerve sprouting after myocardial
      infarction.
AB  - OBJECTIVES: Systemic or local inflammation causes cardiac nerve sprouting and
      consequent arrhythmia. Metoprolol can prevent sympathetic nerve remodeling after
      myocardial infarction (MI), but the underlying mechanism is unclear. In this
      study, we evaluated the role of metoprolol in ameliorating sympathetic sprouting.
      METHODS: Rabbits underwent ligation of the coronary artery for MI. MI rabbits
      received metoprolol or saline for 7 days. Immunohistochemistry was used to
      measure cardiac nerve sprouting and sympathetic innervations. Nuclear factor
      kappaB (NF-kappaB) DNA binding activity was analyzed by electrophoretic mobility
      shift assay. The protein levels of NF-kappaB p65, inhibitor kappaBalpha
      (IkappaBalpha) and nerve growth factor (NGF) were detected by Western blot
      analysis. The mRNA levels of NGF, interleukin-1beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha) were examined by quantitative real-time PCR. RESULTS: MI
      rabbits showed nerve sprouting and sympathetic hyperinnervation. In MI rabbits,
      as compared with saline treatment, metoprolol reduced NF-kappaB DNA binding
      activity and NF-kappaB p65 level, and increased IkappaBalpha level. Moreover,
      metoprolol downregulated IL-1beta, TNF-alpha and NGF levels, and reduced the
      density of sympathetic nerve fibers. CONCLUSIONS: Metoprolol ameliorates
      sympathetic nerve sprouting in rabbits after MI and is associated in part with
      inhibiting NF-kappaB activity.

PMID- 23860331
TI  - Phosphodiesterase V inhibition reduces airway responsiveness, but does not
      improve the beneficial effect of deep inspiration.
AB  - BACKGROUND: Deep inspirations (DIs) can prevent (bronchoprotection; BP) and
      reverse (bronchodilation; BD) methacholine (Mch)-induced bronchoconstriction, but
      this effect is reduced or absent in people with asthma or airways
      hyperresponsiveness (AHR). The mechanisms of this defect are unknown. OBJECTIVE:
      To indirectly examine the role of guanosine 3',5'-cyclic monophosphate (cGMP) by
      testing the hypothesis that the phosphodiesterase (PDE) V inhibitor, sildenafil,
      would improve DI-induced BP in individuals with AHR. METHODS: Thirty-two
      individuals were screened and 15 met all the inclusion/exclusion criteria (7
      subjects with AHR and 8 healthy subjects). A single-dose Mch challenge inducing a
      20% reduction in FEV1 in the absence of DIs was first identified. Thereafter,
      every study participant had 4 pairs of visits, each pair testing DI-induced BP
      and BD against the single-dose Mch, with no drug, or pretreatment with 25, 50 and
      100 mg of sildenafil, respectively, in consecutive order. RESULTS: Sildenafil did
      not influence baseline lung function. However, in the absence of DIs, the drug
      caused a dose-dependent attenuation of the Mch-induced decrease in FEV1 by 17%
      (median value; 25th percentile: 1, 75th percentile: 16), 35% (-3, 61) and 37%
      (13, 79) for the 25-, 50- and 100-mg doses, respectively (p = 0.0004). No
      differences between the two participant groups were found. There were no effects
      of sildenafil on DI-induced BP or BD. CONCLUSION: We infer from these results
      that the mechanism responsible for the defective ability of DIs to protect the
      airways from bronchoconstriction is unlikely to be due to dysregulation of cGMP.
      Of importance, a potential role for PDE V inhibition as a bronchoprotector
      treatment needs to be explored.

PMID- 23860332
TI  - Activation of Gq proteins coupled with 5-HT2 receptors in rat cerebral cortical
      membranes assessed by antibody-capture scintillation proximity assay/[S]GTPgammaS
      binding.
AB  - BACKGROUND/AIMS: Functional activation of Gq coupled with 5-HT2 receptors was
      investigated in rat cerebral cortical membranes. METHODS: Antibody-capture
      scintillation proximity assay (SPA)/[(35)S]GTPgammaS binding with anti-Galphaq
      antibody was performed. RESULTS: The specific [(35)S]GTPgammaS binding to Galphaq
      was increased by 5-hydroxytryptamine (5-HT) in a concentration-dependent but
      unsaturable manner. The increase elicited by micromolar concentrations of 5-HT
      was inhibited completely by ketanserin, whereas it inhibited the response by
      submillimolar to millimolar concentrations of 5-HT only partially. Analysis of
      the concentration-dependent increases by 5-HT in the absence and presence of
      ketanserin, methiothepin, WAY100635, and pirenzepine clearly indicates that there
      are two distinct components of 5-HT-stimulated [(35)S]GTPgammaS binding, one of
      which is a pharmacologically relevant increase elicited by lower concentrations (
      30 MUmol/l) of 5-HT mediated through 5-HT2 receptors and the other is
      pharmacologically undefined stimulation by higher concentrations of 5-HT. When 5
      HT and carbachol were added simultaneously, there was apparently lack of
      additivity. CONCLUSION: It is concluded that by means of antibody-capture
      SPA/[(35)S]GTPgammaS binding it is possible to detect two distinct components of
      5-HT-elicited activation of Gq shared by M1 muscarinic receptors, one of which is
      mediated through 5-HT2 receptors and the other is derived from unknown origin in
      rat cerebral cortical membranes.

PMID- 23860333
TI  - The use of "mixing" procedure of mixed methods in health services research.
AB  - BACKGROUND: Mixed methods research has emerged alongside qualitative and
      quantitative approaches as an important tool for health services researchers.
      Despite growing interest, among health services researchers, in using mixed
      methods designs, little has been done to identify the procedural aspects of doing
      so. PURPOSE: To describe how mixed methods researchers mix the qualitative and
      quantitative aspects of their studies in health services research. DATA SOURCE:
      We searched the PubMed for articles, using mixed methods in health services
      research, published between January 1, 2006 and December 30, 2010. STUDY
      SELECTION: We identified and reviewed 30 published health services research
      articles on studies in which mixed methods had been used. We selected 3 articles
      as illustrations to help health services researcher conceptualize the type of
      mixing procedures that they were using. RESULTS: Three main "mixing" procedures
      have been applied within these studies: (1) the researchers analyzed the 2 types
      of data at the same time but separately and integrated the results during
      interpretation; (2) the researchers connected the qualitative and quantitative
      portions in phases in such a way that 1 approach was built upon the findings of
      the other approach; and (3) the researchers mixed the 2 data types by embedding
      the analysis of 1 data type within the other. CONCLUSIONS: "Mixing" in mixed
      methods is more than just the combination of 2 independent components of the
      quantitative and qualitative data. The use of "mixing" procedure in health
      services research involves the integration, connection, and embedding of these 2
      data components.

PMID- 23860334
TI  - Neurotensin agonists in the regulation of food intake.

PMID- 23860335
TI  - Maternal prepregnancy weight status and associations with children's development
      and disabilities at kindergarten.
AB  - OBJECTIVE: Obesity is prevalent among women of reproductive age, and
      developmental disabilities in children continue to increase. We examined
      associations between mother's prepregnancy body mass index (BMI) and physical and
      developmental disabilities, and objective measures of reading and math skills and
      fine and gross motor function in children. METHODS: We used the Early Childhood
      Longitudinal Study-Birth Cohort (ECLS-B; n=5200), a cohort of children born in
      2001 and followed until kindergarten. Children were classified according to
      maternal prepregnancy BMI (in kg per m(2)): underweight (BMI <18.5), normal
      weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese class I (BMI 30.0-34.9)
      and obese class II/III (BMI >= 35.0). Parent reports of doctor-diagnosed
      disabilities were collected up to kindergarten and classified as learning and
      behavioral or physical. Children's reading and math and fine and gross motor
      function were assessed at kindergarten according to standardized tests. Linear
      and modified logistic regression models were adjusted for maternal
      sociodemographic variables, family enrichment variables, and children's sex, age
      and year of kindergarten entry. Additional adjustment for current child BMI was
      performed in separate models. All data are weighted to be nationally
      representative of the children born in 2001. RESULTS: Compared with children of
      normal-weight mothers, children born to obese class II/III mothers had an
      increased risk of learning or behavioral (risk ratio 1.67; 95% confidence
      interval 1.27, 2.21)), but not physical disabilities (risk ratio 0.57; 95%
      confidence interval 0.27, 1.22). Gross (P<0.001), but not fine (P=0.06) motor
      function was significantly associated with maternal BMI, but gross motor function
      was attenuated after adjustment for current child BMI (P=0.05). Children's
      reading scores (P=0.01) but not math scores (P=0.11) were significantly
      associated with maternal BMI. CONCLUSIONS: In this nationally representative US
      cohort, children born to severely obese mothers had an increased risk for
      diagnosed learning and behavioral but not physical disabilities by kindergarten.

PMID- 23860336
TI  - Pelvic floor dysfunction--does menopause duration matter?
AB  - OBJECTIVE: To explore the effect of menopause and hormone replacement therapy on
      pelvic organ prolapse and pelvic floor muscle function. METHODS: The records of
      patients who attended a tertiary urogynaecological center were reviewed
      retrospectively. A standardised interview included menopausal age, i.e. years
      since last period or onset of menopausal symptoms, current or previous hormone
      use. The clinical examination included prolapse assessment (POP-Q) and palpation
      of the levator ani muscle. 4D transperineal ultrasound, supine and after voiding,
      was performed in all patients. Volume data sets were analysed for pelvic organ
      descent and measures of contractility and distensibility of the pelvic floor at a
      later date, blinded to all clinical data. RESULTS: Of 311 women seen during the
      inclusion period, 65% were postmenopausal. Current systemic or local hormone use
      was reported by 7% and 6%, respectively. 163 women (52%) reported prolapse
      symptoms with a mean bother of 5.7/10. Significant pelvic organ prolapse was
      found on clinical examination (POP-Q stage>=2) in 77%, and diagnosed on
      ultrasound in 61%. On multivariate analysis, controlling for calendaric age,
      parity and levator avulsion, there was no evidence for menopausal age as an
      independent predictor of any symptom and sign of pelvic organ prolapse and pelvic
      floor muscle function. Local oestrogen use and past or present hormone
      replacement therapy had no detectable effect on any pelvic floor parameter.
      CONCLUSIONS: Hormone deficiency following menopause is unlikely to play a major
      role in pelvic organ support and levator ani function. Hence, both do not appear
      to be substantially influenced by local or systemic hormone replacement therapy.

PMID- 23860337
TI  - The centennial of Karl Jaspers'.

PMID- 23860338
TI  - Monitoring of plasma cell-free DNA in predicting postoperative recurrence of
      clear cell renal cell carcinoma.
AB  - BACKGROUND: Circulating cell-free DNA (cfDNA) mostly originates from tumors and
      its level correlates with treatment. We assessed whether the level of plasma
      cfDNA could help monitor recurrence after nephrectomy. METHODS: This study
      included 92 patients with clear cell renal cell carcinoma (cRCC). Quantitative
      real-time PCR was used to measure the level of plasma cfDNA before and after
      nephrectomy. RESULTS: The pretreatment level of plasma cfDNA in patients with
      metastatic cRCC (6.04 +/- 0.72) was significantly higher than in those with
      localized cRCC (5.29 +/- 0.53, p = 0.017) or controls (0.65 +/- 0.29, p < 0.001).
      Of patients with localized cRCC, those with recurrence had a significantly higher
      plasma cfDNA level than those without (p = 0.024). The patients with a high
      plasma cfDNA level had a significantly higher recurrence rate than those with a
      low plasma cfDNA level before and after nephrectomy (p = 0.018). CONCLUSION: The
      level of plasma cfDNA may be useful as a tool to monitor patients during follow
      up and guide further diagnostic work-up for the detection of recurrence.

PMID- 23860339
TI  - Dosimetric consequences of prostate-based couch shifts on the precision of dose
      delivery during simultaneous IMRT irradiation of the prostate, seminal vesicles
      and pelvic lymph nodes.
AB  - INTRODUCTION: To evaluate the impact interfraction prostate (CTV1) motion
      corrections on doses delivered to seminal vesicles (CTV2) and lymph nodes (CTV3),
      and to determine ideal planning target volume (PTV) margins for these targets
      with prostate-based position verification. MATERIAL AND METHODS: Retrospective
      analysis based on 253 cone beam computed tomography (CBCT) studies of 28
      patients. The isocenter-shift method was used to estimate the interfraction
      prostate and bony shift effects on the original plan coverage. Friedman's test
      was used to assess statistical significance between dose-volume histogram (DVH)
      parameters which were calculated for prostate-based sum plans, bony-based sum
      plans and original treatment plans. The van Herk formula was used to determine
      the set-up margin size for prostate-based verification. RESULTS: The tracked
      shifts influenced the minimum, maximum and mean CTV2 and CTV3 doses, with a range
      differential of 0.17%-2.63% (prostate shifts) and 0.13%-1.92% (bony shifts)
      compared to the corresponding original parameters. Friedman's test revealed
      significant differences in the minimum doses to the CTV3 and maximum doses to
      both the CTV2 and CTV3. The calculated set-up margins of 1.22 cm (vertical), 0.19
      cm (longitudinal) and 0.39 cm (lateral) should be added to CTV3 while performing
      prostate-based positioning. CONCLUSION: To avoid geographical miss during
      simultaneous irradiation of independently moving targets (CTV1-3) appropriate
      margins should be used in accordance with the position verification method used.
      Based on our findings the following margin sizes should be used: 0.7 cm for the
      CTV1, 0.8-0.9 cm for the CTV2 , and asymmetric 1.0 cm (vertically) and 0.5 cm
      (other axes) for the CTV3.

PMID- 23860340
TI  - GET-SERF, a new gradient encoded SERF experiment for the trivial edition of 1H
      19F couplings.
AB  - A new spatially encoded heteronuclear (1)H-(19)F selective refocusing NMR
      experiment (GET-SERF) is proposed. This sequence allows editing in one single 2D
      experiment all couplings between a selected fluorine site and all the proton
      nuclei of the molecule. Its efficiency is illustrated in the case of diflunisal,
      a difluorinated anti-inflammatory drug, in isotropic and anisotropic media. 

PMID- 23860341
TI  - British Thoracic Society guideline for diagnostic flexible bronchoscopy in
      adults: accredited by NICE.

PMID- 23860342
TI  - 75As NMR study of overdoped CeFeAsO0.8F0.2.
AB  - We report on the results from a (75)As nuclear magnetic resonance (NMR) study of
      the overdoped iron pnictide superconductor CeFeAsO0.8F0.2. We find two As sites
      with different shifts at temperatures as high as 100 K, which is above the
      superconducting transition temperature of 39 K, and hence they cannot be
      attributed to the effect of vortices in the superconducting state as previously
      suggested (Ghoshray et al 2009 Phys. Rev. B 79 144512). The much larger spin
      lattice relaxation rate compared with that found in other pnictides without
      magnetic rare earth ions, and the temperature dependence of the (75)As NMR shifts
      for the two central lines, are consistent with the hyperfine coupling from
      magnetic Ce to As. The low temperature spectra indicate that there are As ions
      with two different quadrupole splittings. Our findings appear to be consistent
      with an electronic phase segregation into regions with two different F dopings or
      the presence of a correlated spatial charge and spin density variations.

PMID- 23860343
TI  - N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson
      diseases.
AB  - OBJECTIVE: This study aimed to determine if the antioxidant N-acetylcysteine
      (NAC) is able to alter peripheral and central redox capabilities in patients with
      Parkinson disease (PD) or Gaucher disease (GD). METHODS: The study included
      nondemented adult subjects: 3 with PD, 3 with GD, and 3 healthy controls.
      Baseline brain glutathione (GSH) concentrations were measured using 7-T magnetic
      resonance spectroscopy (MRS). Baseline blood reduced-to-oxidized GSH ratios were
      determined for each subject. Brain GSH concentrations and blood redox ratios were
      then determined during and at specified time points after a single, 150-mg/kg NAC
      infusion. RESULTS: N-acetylcysteine increased blood GSH redox ratios in those
      with PD and GD and healthy controls, which was followed by an increase in brain
      GSH concentrations in all subjects. CONCLUSIONS: This is the first demonstration
      that with MRS, it is possible to directly measure and monitor increases in brain
      GSH levels in the human brain in response to a single, intravenous administration
      of NAC. This work shows the potential utility of MRS monitoring, which could
      assist in determining dosing regimens for clinical trials of this potentially
      useful antioxidant therapy for PD disease, GD, and other neurodegenerative
      disorders.

PMID- 23860344
TI  - Adverse effects of antiepileptic drugs in North Indian pediatric outpatients.
AB  - PURPOSE: The present study investigates the pattern and predictors of treatment
      emergent adverse drug reactions (ADRs) in children diagnosed with epilepsy.
      METHODS: We conducted prospective observational study in a tertiary care teaching
      hospital on 277 epileptic children. Antiepileptic drug (AED)-associated ADRs,
      demographic and clinical characteristics, AED regimen, and so on were recorded.
      Causality, severity, and preventability were performed by World Health
      Organization-Uppsala Monitoring Center scale, Hartwig's severity scale, and
      Schumock and Thornton questionnaire, respectively. RESULTS: Of the enrolled
      population, 53% children had symptomatic epilepsy, and 51% were in 5- to 10-year
      age group. More than two-thirds of children were on monotherapy, with phenytoin
      (n = 176, 63.5%) being the most common AED. Three hundred fifty-three AED-related
      ADRs were recorded in 175 children (63.2%). Poor scholastic performance (19%) was
      the most common ADR, followed by gum hypertrophy (13.3%), headache (10.2%),
      behavioral problems (5.7%), drowsiness (5.7%), and others. Two hundred sixteen
      ADRs were probable, and 126 ADRs were possible. Severe ADRs were noted in 6
      children. Girls (odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.07
      3.45; P = 0.03), children with secondary epilepsy (OR, 3.31; 95% CI, 1.76-6.23; P
      <= 0.001), children older than 5 years (5-10 years; OR, 6.28; 95% CI, 2.79-14.12;
      P <= 0.001), and those older than 10 years (OR, 9.04; 95% CI, 3.69-22.17; P <=
      0.001) were found to be at higher risk of experiencing ADRs. CONCLUSIONS:
      Monotherapy was the preferred treatment. Phenytoin was the most common ADR
      causative agent. Female sex, symptomatic epilepsy, and older age (> 5 years) were
      found to be associated with higher probability of ADR development.

PMID- 23860345
TI  - Extended-release dexmethylphenidate 30 mg/d versus 20 mg/d: duration of
      attention, behavior, and performance benefits in children with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: This study aimed to compare the effects of dexmethylphenidate (D-MPH)
      extended-release (ER) 30 mg and D-MPH-ER 20 mg on attention, behavior, and
      performance in children with attention-deficit/hyperactivity disorder. METHODS:
      In a randomized, double-blind, 3-period-by-3-treatment, crossover study, children
      aged 6 to 12 years with attention-deficit/hyperactivity disorder stabilized on
      methylphenidate (40-60 mg/d) or D-MPH (20-30 mg/d) received D-MPH-ER 20 mg/d, 30
      mg/d, and placebo for 7 days each (final dose of each treatment period
      administered in a laboratory classroom). Swanson, Kotkin, Agler, M-Flynn, and
      Pelham (SKAMP) Combined (Attention and Deportment) rating scale and Permanent
      Product Measure of Performance (PERMP) math test assessments were conducted at
      baseline and 3, 6, 9, 10, 11, and 12 hours postdose. RESULTS: A total of 165
      children (94 boys; mean age, 9.6 years) were randomized (162 included in intent
      to-treat analyses). Significant improvements were noted for D-MPH-ER 30 mg over D
      MPH-ER 20 mg at various late time points on the SKAMP scales (Combined scores at
      9, 10, 11, and 12 hours postdose; Attention scores at 10, 11, and 12 hours
      postdose; deportment scores at 9 and 12 hours postdose). The PERMP math test
      attempted and -correct scores (change from predose) were significantly higher
      with D-MPH-ER 30 mg than with D-MPH-ER 20 mg at 10, 11, and 12 hours postdose.
      Both D-MPH-ER doses were superior to placebo at all time points. CONCLUSIONS: D
      MPH-ER 30 mg was superior to D-MPH-ER 20 mg at later time points in the day,
      suggesting that higher doses of D-MPH-ER may be more effective later in the day.

PMID- 23860346
TI  - Covert dyskinesia associated with aripiprazole: a case report and review of the
      literature.
AB  - The atypical antipsychotic agents are felt by many to have a lower risk of
      inducing the development of dyskinetic movements than the conventional
      antipsychotic agents agents such as haloperidol and fluphenazine. However, that
      does not mean that treatment with the atypical antipsychotic agents carries no
      risk of developing dyskinesias. To the contrary, all of the atypical
      antipsychotic agents, including aripiprazole, have been associated with the
      induction of dyskinetic movements. We will present the case of a patient who
      developed a covert dyskinesia that manifested shortly after the discontinuation
      of aripiprazole. We will review the use of aripiprazole and the adverse effects
      most commonly associated with its use. We will also discuss the risk factors
      associated with the development of tardive dyskinesia and review the different
      clinical variations (withdrawal dyskinesia, covert dyskinesia, tardive
      diskinesia) of medication-induced dyskinesias. 

PMID- 23860347
TI  - Single-dose oral lacosamide in refractory simple partial status epilepticus: case
      report and review.
AB  - OBJECTIVES: This study aimed to present 2 patients with simple partial refractory
      status epilepticus (RSE) treated with a single oral lacosamide (LCM) dose and to
      review the literature on this topic. METHOD: A retrospective description of 2
      patients with simple partial RSE treated with 300 mg of LCM per os (p.o.) and a
      literature review were done. RESULTS: Both patients responded to single-dose oral
      LCM treatment with seizure cessation after 30 minutes. CONCLUSIONS: This is the
      first report on successful treatment of simple partial RSE with a single-dose of
      LCM p.o.. Oral LCM might represent an option for treatment of patients presenting
      with simple partial RSE.

PMID- 23860349
TI  - Fine-needle aspiration of primary Langerhans cell histiocytosis of the thyroid
      gland, a potential mimic of papillary thyroid carcinoma.
AB  - BACKGROUND: The clinical presentation of Langerhans cell histiocytosis (LCH) as a
      primary solitary nodule in the thyroid gland is rare. As a result, there are few
      reports of its cytologic features in thyroid aspirates where it can pose a
      diagnostic pitfall. CASE AND CONCLUSION: To foster familiarity with its
      cytomorphology, we report the fine-needle aspiration biopsy (FNAB) findings of 3
      specimens from 2 patients with LCH presenting as a solitary thyroid nodule. All
      aspirates contained numerous dispersed cells with prominent nuclear grooves, and
      the background showed a mixed pattern of chronic inflammation including scattered
      eosinophils. The aspirate from patient 1 raised a differential diagnosis that
      included chronic lymphocytic thyroiditis and a thyroglossal duct cyst, while the
      aspirate from patient 2 was interpreted as 'suspicious for papillary thyroid
      carcinoma'. The diagnosis of LCH was confirmed in both patients after lobectomy
      and immunohistochemical studies that revealed positive reactivity for CD1a and S
      100. LCH of the thyroid gland is rare and can pose significant diagnostic
      challenges, but increased familiarity with its characteristic cytomorphology can
      help in avoiding diagnostic pitfalls.

PMID- 23860348
TI  - Plant calcium-permeable channels.

PMID- 23860352
TI  - Changing radiology in the changing hospital environment.

PMID- 23860350
TI  - Fluoxetine induced suicidal erythrocyte death.
AB  - The antidepressant fluoxetine inhibits ceramide producing acid sphingomyelinase.
      Ceramide is in turn known to trigger eryptosis the suicidal death of erythrocytes
      characterized by cell shrinkage and exposure of phosphatidylserine at the
      erythrocyte surface. Ceramide is effective through sensitizing the erythrocytes
      to the pro-eryptotic effect of increased cytosolic Ca2+ activity ([Ca2+]i). In
      nucleated cells, fluoxetine could either inhibit or stimulate suicidal death or
      apoptosis. The present study tested whether fluoxetine influences eryptosis. To
      this end cell volume was estimated from forward scatter, phosphatidylserine
      exposure from annexin V binding, hemolysis from hemoglobin release and [Ca2+]i
      from Fluo-3 fluorescence intensity. As a result, a 48 h exposure of erythrocytes
      to fluoxetine (>=25 uM) significantly decreased forward scatter, increased
      annexin V binding and enhanced [Ca2+]i. The effect on annexin V binding was
      significantly blunted, but not abolished, in the absence of extracellular Ca2+.
      In conclusion, fluoxetine stimulates eryptosis, an effect at least in part due to
      increase of cytosolic Ca2+ activity. 

PMID- 23860353
TI  - MR siting: improving efficiency and safety.

PMID- 23860354
TI  - Evaluation of the cerebrospinal fluid amyloid-beta1-42/amyloid-beta1-40 ratio
      measured by alpha-LISA to distinguish Alzheimer's disease from other dementia
      disorders.
AB  - BACKGROUND: The well-established core biomarkers used to identify Alzheimer's
      disease (AD) overlap with other dementia disorders such as dementia with Lewy
      bodies (DLB) and Parkinson's disease with dementia (PDD). This study aimed to
      evaluate whether the cerebrospinal fluid (CSF) amyloid-beta (Abeta)1-42/Abeta1-40
      ratio, measured by a novel method, could improve the differential diagnosis of
      AD, DLB and PDD. METHOD: CSF levels of Abeta1-40 and Abeta1-42 in patients with
      PDD, DLB, AD, Parkinson's disease and controls were analyzed using an amplified
      luminescent proximity homogenous immunoassay along with conventional
      immunoassays. RESULTS: The CSF Abeta1-42/Abeta1-40 ratio increased discrimination
      of AD from PDD and DLB compared with either of the two Abeta biomarkers
      individually. CONCLUSION: The use of the Abeta1-42/Abeta1-40 ratio could improve
      the differentiation of AD from PDD and DLB.

PMID- 23860351
TI  - Mini-review: novel therapeutic strategies to blunt actions of pneumolysin in the
      lungs.
AB  - Severe pneumonia is the main single cause of death worldwide in children under
      five years of age. The main etiological agent of pneumonia is the G+ bacterium
      Streptococcus pneumoniae, which accounts for up to 45% of all cases.
      Intriguingly, patients can still die days after commencing antibiotic treatment
      due to the development of permeability edema, although the pathogen was
      successfully cleared from their lungs. This condition is characterized by a
      dramatically impaired alveolar epithelial-capillary barrier function and a
      dysfunction of the sodium transporters required for edema reabsorption, including
      the apically expressed epithelial sodium channel (ENaC) and the basolaterally
      expressed sodium potassium pump (Na+-K+-ATPase). The main agent inducing this
      edema formation is the virulence factor pneumolysin, a cholesterol-binding pore
      forming toxin, released in the alveolar compartment of the lungs when pneumococci
      are being lysed by antibiotic treatment or upon autolysis. Sub-lytic
      concentrations of pneumolysin can cause endothelial barrier dysfunction and can
      impair ENaC-mediated sodium uptake in type II alveolar epithelial cells. These
      events significantly contribute to the formation of permeability edema, for which
      currently no standard therapy is available. This review focuses on discussing
      some recent developments in the search for the novel therapeutic agents able to
      improve lung function despite the presence of pore-forming toxins. Such
      treatments could reduce the potentially lethal complications occurring after
      antibiotic treatment of patients with severe pneumonia. 

PMID- 23860355
TI  - Effects of the angiotensin-(1-7) receptor Mas on cell proliferation and on the
      population of doublecortin positive cells within the dentate gyrus and the
      piriform cortex.
AB  - Aside 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 G protein-coupled receptor being essential for angiotensin-(1
      7) signaling. Mas is not only expressed in the periphery but also within the
      brain, e.g. in the dentate gyrus (DG) and the piriform cortex (PC). Since the DG
      is capable of adult neurogenesis, we examined the impact of a deletion of Mas
      upon adult neurogenesis. Deletion of Mas did not alter cell proliferation in the
      adult DG (as monitored with phosphohistone H3) and did not alter cell death (as
      monitored with activated Caspase 3). However, Mas deficiency resulted in an
      increase in the number of doublecortin (DCX) positive cells, indicating that lack
      of Mas increases the number of this cell population. Concerning the PC, it is
      discussed whether adult neurogenesis occurs under physiological conditions in
      this area. We could demonstrate that Mas deficiency has an impact on cell
      division and on the population of DCX-positive cells within the PC. Since Mas is
      not expressed before birth within the brain, our data may suggest that adult
      hippocampal neurogenesis and neurogenesis occurring during prenatal development
      share several common mechanisms, but are, at least in part, differentially
      regulated. Moreover, since deficiency for Mas increases the numbers of DCX
      positive young neurons, blockage of Mas might be beneficial in stimulating
      neurogenesis in adults. 

PMID- 23860356
TI  - Schizophrenia and dopamine receptors.
AB  - Schizophrenia patients are behaviorally supersensitive to dopamine-like drugs
      such as amphetamine or methylphenidate, meaning that patients respond to such
      drugs with increased psychotic symptoms, as compared to control subjects. A basis
      of such supersensitivity may be an increased pre-synaptic release of dopamine or
      a post-synaptic elevation of D2 receptors or of D2High receptors in active stages
      of schizophrenia. While the pre-synaptic release of dopamine is normal in stable
      patients with schizophrenia, brain imaging studies find that D2 receptors are
      increased by an average of 5.8% in antipsychotic-free schizophrenia patients. It
      is possible that the behavioral supersensitivity may stem from more D2High
      receptors in schizophrenia. Although the antipsychotic/dopamine D2 receptor can
      exist in vitro in a state of high affinity for dopamine (as D2High), or in a
      state of low affinity for dopamine (as D2Low), there is no clear evidence that
      D2High states can be selectively labeled or stably exist in vivo. Nevertheless,
      two studies revealed an 80% increase in apparent D2High receptors in
      schizophrenia patients after reducing endogenous dopamine. The elevation in
      apparent D2High receptors in vivo in schizophrenia matches the elevation in
      D2High receptors in vitro in animal models of psychosis, including dopamine
      supersensitive animals pretreated with amphetamine, marijuana, or phencyclidine,
      or animals with gene knockouts in various neurotransmitter pathways, including
      those for glutamate receptors. The elevation of D2High receptors in vitro and the
      increased apparent D2High receptors in vivo is consistent with behavioral
      dopamine supersensitivity in schizophrenia patients.

PMID- 23860357
TI  - Long-term remodeling of rat pial microcirculation after transient middle cerebral
      artery occlusion and reperfusion.
AB  - OBJECTIVE: The aim of this study was to assess the in vivo structural and
      functional remodeling of pial arteriolar networks in the ischemic area of rats
      submitted to transient middle cerebral artery occlusion (MCAO) and different time
      intervals of reperfusion. METHODS AND RESULTS: Two closed cranial windows were
      implanted above the left and right parietal cortex to observe pial
      microcirculation by fluorescence microscopy. The geometric characteristics of
      pial arteriolar networks, permeability increase, leukocyte adhesion and capillary
      density were analyzed after 1 h or 1, 7, 14 or 28 days of reperfusion. MCAO and 1
      hour reperfusion caused marked microvascular changes in pial networks. The
      necrotic core was devoid of vessels, while the penumbra area presented a few
      arterioles, capillaries and venules with severe neuronal damage. Penumbra
      microvascular permeability and leukocyte adhesion were pronounced. At 7 days of
      reperfusion, new pial arterioles were organized in anastomotic vessels,
      overlapping the ischemic core and in penetrating pial arterioles. Vascular
      remodeling caused different arteriolar rearrangement up to 28 days of reperfusion
      and animals gradually regained their motor and sensory functions. CONCLUSIONS:
      Transient MCAO-induced pial-network remodeling is characterized by arteriolar
      anastomotic arcades. Remodeling mechanisms appear to be accompanied by an
      increased expression of nitric oxide synthases.

PMID- 23860358
TI  - Nature and severity of menopausal symptoms and their impact on quality of life
      and sexual function in cancer survivors compared with women without a cancer
      history.
AB  - OBJECTIVE: After cancer treatment, troublesome menopausal symptoms are common but
      poorly understood. Using standardized instruments, we measured differences in
      symptom nature, severity, impact on quality of life, and sexual function between
      cancer survivors and noncancer participants. METHODS: The Menopause Symptoms
      After Cancer Clinic operates within the general menopause service in a large
      women's hospital, providing menopause advice and management to women with
      menopausal symptoms and a cancer history. Menopausal symptoms were recorded using
      the Greene Climacteric Scale, past-week symptoms were recorded using the
      Functional Assessment of Cancer Therapy breast cancer subscale and endocrine
      symptom subscale, and sexual symptoms were recorded using Fallowfield's Sexual
      Activity Questionnaire. RESULTS: Cancer survivors (n = 934) and noncancer
      participants (n = 155) did not significantly differ by age at menopause (46 y) or
      age at first clinic visit (51 y). Cancer survivors were more likely than
      noncancer participants to be severely troubled by vasomotor symptoms (hot flushes
      and night sweats; odds ratio, 1.71; 95% CI, 1.06-2.74) and reported more frequent
      (6.0 vs 3.1 in 24 h; P < 0.001) and more severe (P = 0.008) hot flushes. In
      contrast, cancer survivors were significantly less troubled by psychological and
      somatic symptoms and reported better quality of life than noncancer participants.
      Groups did not differ significantly in physical or functional well-being,
      gynecologic symptom severity, or sexual function. CONCLUSIONS: Cancer survivors
      are more troubled by vasomotor symptoms than noncancer participants, but
      noncancer participants report greater psychological symptoms. Sexual function
      does not differ. An improved understanding of the nature and impact of menopause
      on cancer survivors can be used to direct management protocols.

PMID- 23860359
TI  - The trouble with trabeculation.

PMID- 23860360
TI  - An unusual cause of urinary retention in a young female: a case report.
AB  - Inflammatory myofibroblastic tumors are commonly seen in young adults and
      adolescents and commonly present with painless hematuria. We report a case of a
      38-year-old woman who presented to us with urinary retention due to a prolapsing
      tumor mass from the urethra, which was discovered to be an inflammatory
      myofibroblastic tumor arising from the bladder base and involving the bladder
      neck. The patient underwent a successful transurethral resection of the tumor and
      at 6-month follow-up was continent and symptom-free.

PMID- 23860361
TI  - Bioactive insulin microparticles produced by supercritical fluid assisted
      atomization with an enhanced mixer.
AB  - Supercritical fluid assisted atomization introduced by a hydrodynamic cavitation
      mixer (SAA-HCM) was used to micronize insulin from aqueous solution without use
      of any organic solvents. Insulin microparticles produced under different
      operating conditions including solution type, solution concentration and
      precipitator temperature presented distinct morphologies such as highly folded,
      partly deflated, corrugated or smooth hollow spherical shape. Solution
      concentration had a striking influence on particle size, and insulin
      microparticles produced from acidic solution had mean diameters increasing from
      1.4 MUm to 2.7 MUm when protein concentration increased from 3g/L to 50 g/L. HPLC
      chromatograms showed no degradation of insulin after SAA-HCM processing and FTIR,
      CD and fluorescence data further confirmed the structural stability. TGA analysis
      revealed that insulin microparticles remained moderate moisture content compared
      with raw material. In vivo study showed that insulin processed by SAA-HCM from
      acidic solution retained identical bioactivity. SAA-HCM is demonstrated to be a
      very promising process for insulin inhaled formulation development.

PMID- 23860362
TI  - Warkmycin, a novel angucycline antibiotic produced by Streptomyces sp. Acta
      2930*.
AB  - A novel angucycline-type antibiotic, warkmycin, was isolated from the culture
      filtrate of Streptomyces strain Acta 2930. Its chemical structure was elucidated
      by HR-MS, one-dimensional and 2D NMR experiments. The compound inhibits the
      growth of Gram-positive bacteria and shows a strong antiproliferative activity
      against mouse fibroblast cell line NIH-3T3 and human cancer cell lines HepG2 and
      HT29. 

PMID- 23860363
TI  - New phenethylamine derivatives from Arenibacter nanhaiticus sp. nov. NH36A(T) and
      their antimicrobial activity.
AB  - Five new phenethylamine (PEA) derivatives (1-5) were isolated from the strain of
      Arenibacter nanhaiticus sp. nov. NH36A(T) derived from the marine sediment of the
      South China Sea by bioassay-guided fractionation. Their structures were
      elucidated by spectroscopic methods including UV, IR, HR-MS and NMR.
      Interestingly, compounds 1-4 existed as enantiomers, which were resolved by
      chiral liquid chromatography. The resolved configuration of each enantiomer was
      assigned by the Marfey's method. Of these compounds, 5 showed weak antimicrobial
      activity against Staphylococcus aureus and Bacillus subtilis with MIC values of
      0.50 and 0.25 mg ml(-1), respectively.

PMID- 23860364
TI  - Ruptured dissecting vertebrobasilar aneurysm in childhood: what is the
      therapeutic strategy?
AB  - BACKGROUND/AIMS: Pediatric aneurysms are rare, accounting for 0.5-4.6% of all
      intracranial aneurysms. Dissecting vertebrobasilar aneurysms (DVBA) are more
      frequently observed among children than adults. Cases acutely presenting with
      subarachnoid hemorrhage need a prompt treatment because of the higher mortality
      related to untreated cases. Options for an active DVBA management depend on the
      features of the malformation and include endovascular and surgical approaches.
      METHODS: We refer to an 8-year-old healthy female, who presented with a sudden
      severe headache and vomit, followed by a half-hour loss of consciousness. A CT
      scan revealed subarachnoid hemorrhage, and brain MR angiography showed a lesion
      with mass effect on bulbar structures, suggestive of an aneurysm of the
      vertebrobasilar junction. The intracranial angiography confirmed this diagnosis
      and showed a relevant revascularization coming from the anterior cerebral
      circulation. RESULTS: Endovascular treatment was considered as a suitable option
      and occlusion of both vertebral arteries, saving the left posterior inferior
      cerebellar artery, was performed. No neurological deficits appeared after
      embolization, and the patient was clinically stable at 18 months of follow-up.
      CONCLUSION: In the 'stent era', parent vessel deconstruction throughout
      endovascular balloon or coil occlusion could be considered in patients with a
      sound collateral circulation and when cerebellar hemisphere and encephalic trunk
      feeding is not compromised.

PMID- 23860365
TI  - Cholesteatoma of the hypotympanum in a patient with Treacher Collins syndrome.
AB  - In the present article we report a cholesteatoma of the hypotympanum extending to
      the jugular foramen in a 16-year-old male with Treacher Collins syndrome.
      Preoperative imaging excluded jugular paraganglioma and set the diagnosis of
      cholesteatoma. We discuss the operative treatment via a large hypotympanotomy and
      creation of an open hypotympanic cavity. To the authors' knowledge this is the
      first description of hypotympanal cholesteatoma with such an extension, being
      treated through this approach. 

PMID- 23860367
TI  - Tips for a physician in getting the right job, part II: the curriculum vitae,
      cover letter, and personal statement.
AB  - It is very important that a job seeker prepares an excellent curriculum vitae
      (CV) and cover letter. Often a personal statement is also needed. If these are
      not done well, often an interview is not granted. There are different formats and
      headings for the CV, depending on the type of job sought and the institution the
      job is located in. There are also some differences in how this is done between
      different countries. However, there are also many common elements of a proper CV.

PMID- 23860366
TI  - Baseline IGF-I levels determine insulin secretion and insulin sensitivity during
      the first year on growth hormone therapy in children born small for gestational
      age. Results from a North European Multicentre Study (NESGAS).
AB  - OBJECTIVE: Developmental programming alters growth and metabolic outcome in
      children born small for gestational age (SGA). We explored insulin and glucose
      metabolism in SGA children treated with a fixed GH dose over 1 year. METHODS: In
      the North European Small for Gestational Age Study (NESGAS), 110 short SGA
      children received GH at 67 ug/kg/day for 1 year. Insulin secretion was assessed
      by acute insulin response (AIR), insulin sensitivity (IS) by HOMA and disposition
      index (DI) by insulin secretion adjusted for IS. RESULTS: First-year GH therapy
      led to increases in height and IGF-I standard deviation score (SDS), and
      reductions in IS (p < 0.0001). Compensatory increases in AIR (p < 0.0001) were
      insufficient and resulted in reduced DI (p = 0.032). Children in the highest IGF
      I SDS tertile at baseline were the least insulin sensitive at baseline (p =
      0.024) and 1 year (p = 0.006). IGF-I responses after 1 year were positively
      related to AIR (r = 0.30, p = 0.007) and DI (r = 0.29, p = 0.005). CONCLUSION: In
      SGA children treated with a high GH dose for 1 year, baseline IGF-I levels were
      related to IS whilst gains in height and IGF-I responses were associated with
      insulin secretion. Defining heterogeneity in IGF-I in SGA children may be useful
      in predicting growth and metabolic response.

PMID- 23860368
TI  - Dynamic optimization of walker-assisted FES-activated paraplegic walking:
      simulation and experimental studies.
AB  - In this paper, we propose a musculoskeletal model of walker-assisted FES
      activated paraplegic walking for the generation of muscle stimulation patterns
      and characterization of the causal relationships between muscle excitations,
      multi-joint movement, and handle reaction force (HRF). The model consists of the
      lower extremities, trunk, hands, and a walker. The simulation of walking is
      performed using particle swarm optimization to minimize the tracking errors from
      the desired trajectories for the lower extremity joints, to reduce the
      stimulations of the muscle groups acting around the hip, knee, and ankle joints,
      and to minimize the HRF. The results of the simulation studies using data
      recorded from healthy subjects performing walker-assisted walking indicate that
      the model-generated muscle stimulation patterns are in agreement with the EMG
      patterns that have been reported in the literature. The experimental results on
      two paraplegic subjects demonstrate that the proposed methodology can improve
      walking performance, reduce HRF, and increase walking speed when compared to the
      conventional FES-activated paraplegic walking. 

PMID- 23860369
TI  - Investigation of an acoustic-mechanical method to detect implant loosening.
AB  - Precise diagnosis of loosening of endoprosthetic implants plays an important role
      in timely, adequate treatment. However, today's diagnostic tools, mainly
      radiological evaluation, do not yield satisfactory results. Therefore, a new
      approach based on the transmission of an internally generated combined acoustic
      and vibration signal, was investigated. For signal generation, a magnetic
      oscillator which impinges inside an implant component, can be used. The signal
      can be detected by an external accelerometer being positioned on the skin
      surface. Differences in the signal generated result from varying degrees of
      implant fixation. This principle was tested in seven porcine foreleg specimens
      with a custom implant. Influence of the measurement location at the porcine skin
      and different levels of fixation were investigated (pressfit, slight loosening,
      advanced loosening), with regard to the pull-out strength. Evaluation of
      different parameters, especially the frequency spectrum resulted in differences
      of up to 12% for the comparison between pressfit and slight loosening, and 30%
      between pressfit and advanced loosening. A significant correlation between the
      measured frequency and the pull-out strength for different levels of fixation was
      found. Thus, the novel diagnostic method shows potential for the precise
      detection of implant loosening. Further work is required to determine the
      sensitivity and specificity of the proposed system in animal experiments. 

PMID- 23860370
TI  - Current challenges in leprosy research.

PMID- 23860371
TI  - Human mobility and the worldwide impact of intentional localized highly
      pathogenic virus release.
AB  - The threat of bioterrorism and the possibility of accidental release have spawned
      a growth of interest in modeling the course of the release of a highly pathogenic
      agent. Studies focused on strategies to contain local outbreaks after their
      detection show that timely interventions with vaccination and contact tracing are
      able to halt transmission. However, such studies do not consider the effects of
      human mobility patterns. Using a large-scale structured metapopulation model to
      simulate the global spread of smallpox after an intentional release event, we
      show that index cases and potential outbreaks can occur in different continents
      even before the detection of the pathogen release. These results have two major
      implications: i) intentional release of a highly pathogenic agent within a
      country will have global effects; ii) the release event may trigger outbreaks in
      countries lacking the health infrastructure necessary for effective containment.
      The presented study provides data with potential uses in defining contingency
      plans at the National and International level. 

PMID- 23860372
TI  - An effective fitting scheme for the dynamic structure of pure liquids.
AB  - A scheme of analysis for the dynamic structure functions in pure liquids is
      presented which can be implemented with both experimental and simulation data.
      Expressions for contributions of relaxing and propagating modes proposed earlier
      in the framework of the generalized collective modes approach are optimized in
      order to strictly fulfil three among the required sum-rules. The method is
      applied to simulation data for liquid cesium, the description of which appears to
      only require one relaxing and one propagating mode in the investigated wavevector
      range. These expressions are able to account for the dynamics in both the
      hydrodynamic and the kinetic regimes, being quantitatively accurate up to the
      onset of the first peak of the static structure factor and qualitatively beyond.
      Features of the modes can thus be obtained easily, without resorting to heavy
      formalism. The scheme of analysis can be straightforwardly extended to account
      for a higher number of relaxing and propagating modes. 

PMID- 23860373
TI  - Adenosine A2A receptor contributes to ischemic brain damage in newborn piglet.
AB  - Pharmacologic inactivation or genetic deletion of adenosine A2A receptors
      protects ischemic neurons in adult animals, but studies in neonatal hypoxia
      ischemia (H-I) are inconclusive. The present study in neonatal piglets examined
      the hypothesis that A2A receptor signaling after reoxygenation from global H-I
      contributes to injury in highly vulnerable striatal neurons where A2A receptors
      are enriched. A2A receptor immunoreactivity was detected in striatopallidal
      neurons. In nonischemic piglets, direct infusion of the selective A2A receptor
      agonist CGS 21680 through microdialysis probes into putamen increased
      phosphorylation of N-methyl-D-aspartic acid (NMDA) receptor NR1 subunit and
      Na(+),K(+)-ATPase selectively at protein kinase A (PKA)-sensitive sites. In
      ischemic piglets, posttreatment with SCH 58261, a selective A2A receptor
      antagonist, improved early neurologic recovery and preferentially protected
      striatopallidal neurons. SCH 58261 selectively inhibited the ischemia-induced
      phosphorylation of NR1, Na(+),K(+)-ATPase, and cAMP-regulated phosphoprotein 32
      KDa (DARPP32) at PKA-sensitive sites at 3 hours of recovery and improved
      Na(+),K(+)-ATPase activity. SCH 58261 also suppressed ischemia-induced protein
      nitration and oxidation. Thus, A2A receptor activation during reoxygenation
      contributes to the loss of a subpopulation of neonatal putamen neurons after H-I.
      Its toxic signaling may be related to DARPP32-dependent phosphorylation of PKA
      sensitive sites on NR1 and Na(+),K(+)-ATPase, thereby augmenting excitotoxicity
      induced oxidative stress after reoxygenation.

PMID- 23860374
TI  - TNF-alpha induces phenotypic modulation in cerebral vascular smooth muscle cells:
      implications for cerebral aneurysm pathology.
AB  - Little is known about vascular smooth muscle cell (SMC) phenotypic modulation in
      the cerebral circulation or pathogenesis of intracranial aneurysms. Tumor
      necrosis factor-alpha (TNF-alpha) has been associated with aneurysms, but
      potential mechanisms are unclear. Cultured rat cerebral SMCs overexpressing
      myocardin induced expression of key SMC contractile genes (SM-alpha-actin, SM
      22alpha, smooth muscle myosin heavy chain), while dominant-negative cells
      suppressed expression. Tumor necrosis factor-alpha treatment inhibited this
      contractile phenotype and induced pro-inflammatory/matrix-remodeling genes
      (monocyte chemoattractant protein-1, matrix metalloproteinase-3, matrix
      metalloproteinase-9, vascular cell adhesion molecule-1, interleukin-1 beta).
      Tumor necrosis factor-alpha increased expression of KLF4, a known regulator of
      SMC differentiation. Kruppel-like transcription factor 4 (KLF4) small interfering
      RNA abrogated TNF-alpha activation of inflammatory genes and suppression of
      contractile genes. These mechanisms were confirmed in vivo after exposure of rat
      carotid arteries to TNF-alpha and early on in a model of cerebral aneurysm
      formation. Treatment with the synthesized TNF-alpha inhibitor 3,6
      dithiothalidomide reversed pathologic vessel wall alterations after induced
      hypertension and hemodynamic stress. Chromatin immunoprecipitation assays in vivo
      and in vitro demonstrated that TNF-alpha promotes epigenetic changes through KLF4
      dependent alterations in promoter regions of myocardin, SMCs, and inflammatory
      genes. In conclusion, TNF-alpha induces phenotypic modulation of cerebral SMCs
      through myocardin and KLF4-regulated pathways. These results demonstrate a novel
      role for TNF-alpha in promoting a pro-inflammatory/matrix-remodeling phenotype,
      which has important implications for the mechanisms behind intracranial aneurysm
      formation. 

PMID- 23860375
TI  - The effects of focal epileptic activity on regional sensory-evoked neurovascular
      coupling and postictal modulation of bilateral sensory processing.
AB  - While it is known that cortical sensory dysfunction may occur in focal
      neocortical epilepsy, it is unknown whether sensory-evoked neurovascular coupling
      is also disrupted during epileptiform activity. Addressing this open question may
      help to elucidate both the effects of focal neocortical epilepsy on sensory
      responses and the neurovascular characteristics of epileptogenic regions in
      sensory cortex. We therefore examined bilateral sensory-evoked neurovascular
      responses before, during, and after 4-aminopyridine (4-AP, 15 mmol/L, 1 MUL)
      induced focal neocortical seizures in right vibrissal cortex of the rat.
      Stimulation consisted of electrical pulse trains (16 seconds, 5 Hz, 1.2 mA)
      presented to the mystacial pad. Consequent current-source density neural
      responses and epileptic activity in both cortices and across laminae were
      recorded via two 16-channel microelectrodes bilaterally implanted in vibrissal
      cortices. Concurrent two-dimensional optical imaging spectroscopy was used to
      produce spatiotemporal maps of total, oxy-, and deoxy-hemoglobin concentration.
      Compared with control, sensory-evoked neurovascular coupling was altered during
      ictal activity, but conserved postictally in both ipsilateral and contralateral
      vibrissal cortices, despite neurovascular responses being significantly reduced
      in the former, and enhanced in the latter. Our results provide insights into
      sensory-evoked neurovascular dynamics and coupling in epilepsy, and may have
      implications for the localization of epileptogenic foci and neighboring eloquent
      cortex.

PMID- 23860377
TI  - The effect of (NH4)2Sx passivation on the (311)A GaAs surface and its use in
      AlGaAs/GaAs heterostructure devices.
AB  - We have studied the efficacy of (NH4)2Sx surface passivation on the (311)A GaAs
      surface. We report XPS studies of simultaneously-grown (311)A and (100)
      heterostructures showing that the (NH4)2Sx solution removes surface oxide and
      sulfidizes both surfaces. Passivation is often characterized using
      photoluminescence measurements; we show that while (NH4)2Sx treatment gives a 40
      60 *  increase in photoluminescence intensity for the (100) surface, an increase
      of only 2-3 *  is obtained for the (311)A surface. A corresponding lack of
      reproducible improvement in the gate hysteresis of (311)A heterostructure
      transistor devices made with the passivation treatment performed immediately
      prior to gate deposition is also found. We discuss possible reasons why sulfur
      passivation is ineffective for (311)A GaAs, and propose alternative strategies
      for passivation of this surface. 

PMID- 23860376
TI  - Serum microRNA-21 and microRNA-221 as potential biomarkers for cerebrovascular
      disease.
AB  - BACKGROUND/AIMS: MicroRNA miR-21, miR-221 and miR-145 have been implicated in the
      cardiovascular system. We aimed to compare the serum levels of the three
      microRNAs (miRNAs) in different severities of cerebrovascular diseases and
      evaluate the feasibility of using these miRNAs as biomarkers for stroke. METHODS:
      We enrolled 167 subjects with ischemic stroke, 66 atherosclerosis subjects with
      any carotid plaque score and 157 healthy controls. These three types of subjects
      represent three levels of severity in cerebrovascular diseases. Analysis of
      covariance was used to evaluate the relationship between miRNAs and disease
      severity with adjustment for conventional risk factors. To test the prediction
      for stroke, we built regression models containing the serum miRNA levels and risk
      factors. Prediction capabilities were compared by the receiver operating
      characteristic curves. RESULTS: Stroke patients and atherosclerosis subjects had
      significantly higher miR-21 and lower miR-221 serum levels than healthy controls,
      while the miR-145 expression was too low to provide useful information in this
      regard. The best model showed that miR-21 and miR-221 were independent
      predictors. There was a 6.2-fold increase for stroke risk when miR-21 levels
      increase by log102(-DeltaCt) = 1, while a 10.4-fold increase was observed as miR
      221 decreases by log102(-DeltaCt) = 1. CONCLUSIONS: Serum miR-145 was not
      detected in over 50% of the patients and it may not be an ideal marker to predict
      stroke. MiR-21 and miR-221 are novel biomarkers for atherosclerosis and stroke.

PMID- 23860379
TI  - Participatory research towards co-management: lessons from artisanal fisheries in
      coastal Uruguay.
AB  - Participatory research has become increasingly common in natural resources
      management. Even though participatory research is considered a strategy to
      facilitate co-management, there is little empirical evidence supporting this. The
      objective of the present paper is to analyze the contributions of participatory
      research to help encourage the emergence of co-management, based on a case study
      in Piriapolis artisanal fishery in coastal Uruguay (where management has been top
      down). We argue that participatory research involving artisanal fishers,
      government, and other stakeholders (university scientists and NGOs) can be a key
      stimulus towards co-management. We build this argument by considering "seven
      faces" by which co-management can be analyzed: (1) as power sharing; (2) as
      institution building; (3) as trust building; (4) as process; (5) as learning and
      knowledge co-production; (6) as problem solving; and (7) as governance. Our
      findings show that participatory research had an impact on these various faces:
      (1) power was shared when making research decisions; (2) a multi-stakeholder
      group (POPA), with a common vision and goals, was created; (3) trust among
      participants increased; (4) the process of group formation was valued by
      participants; (5) stakeholders learned skills for participation; (6) two problem
      solving exercises were conducted; and (7) a diversity of stakeholders of the
      initial problem identified by fishers (sea lions' impact on long-line fishery)
      participated in the process. The case shows that participatory research functions
      as a platform which enhances learning and knowledge co-production among
      stakeholders, paving the way towards future co-management. 

PMID- 23860380
TI  - Habitat monitoring in the wider countryside: a case study on the pursuit of
      innovation in red deer management.
AB  - Policy frameworks for protected areas, such as the EU habitats directive, ensure
      that environmental monitoring takes place to assess the condition of these sites.
      However, this monitoring rarely extends to the wider countryside, and there is no
      obligation for private landowners to detect trends in habitat condition. Using
      the diffusion of innovations model as an analytical framework we conducted a
      series of semi-structured interviews to consider the uptake of habitat impact
      assessment methods throughout a community involved in private land use pursuits
      in Scotland. It was found that although the community as a whole recognises the
      benefits of habitat impact assessments there are a number of barriers to their
      uptake, including the complexity of data gathering and interpretation, and
      uncertainty around who should be responsible for the conduct of assessments.
      Analysing the uptake of an innovation at an early stage, rather than
      retrospectively as is commonly done, highlights the potential for non-adoption
      and could therefore inform the reinvention of the innovation. In this instance
      reinvention could lead to more appropriate monitoring methods, which, if taken
      up, could reduce the need for legislative intervention in situations where both
      public and private interests need to be considered. 

PMID- 23860378
TI  - Oncogenes and inflammation rewire host energy metabolism in the tumor
      microenvironment: RAS and NFkappaB target stromal MCT4.
AB  - Here, we developed a model system to evaluate the metabolic effects of
      oncogene(s) on the host microenvironment. A matched set of "normal" and
      oncogenically transformed epithelial cell lines were co-cultured with human
      fibroblasts, to determine the "bystander" effects of oncogenes on stromal cells.
      ROS production and glucose uptake were measured by FACS analysis. In addition,
      expression of a panel of metabolic protein biomarkers (Caveolin-1, MCT1, and
      MCT4) was analyzed in parallel. Interestingly, oncogene activation in cancer
      cells was sufficient to induce the metabolic reprogramming of cancer-associated
      fibroblasts toward glycolysis, via oxidative stress. Evidence for "metabolic
      symbiosis" between oxidative cancer cells and glycolytic fibroblasts was provided
      by MCT1/4 immunostaining. As such, oncogenes drive the establishment of a stromal
      epithelial "lactate-shuttle", to fuel the anabolic growth of cancer cells.
      Similar results were obtained with two divergent oncogenes (RAS and NFkappaB),
      indicating that ROS production and inflammation metabolically converge on the
      tumor stroma, driving glycolysis and upregulation of MCT4. These findings make
      stromal MCT4 an attractive target for new drug discovery, as MCT4 is a shared
      endpoint for the metabolic effects of many oncogenic stimuli. Thus, diverse
      oncogenes stimulate a common metabolic response in the tumor stroma. Conversely,
      we also show that fibroblasts protect cancer cells against oncogenic stress and
      senescence by reducing ROS production in tumor cells. Ras-transformed cells were
      also able to metabolically reprogram normal adjacent epithelia, indicating that
      cancer cells can use either fibroblasts or epithelial cells as "partners" for
      metabolic symbiosis. The antioxidant N-acetyl-cysteine (NAC) selectively halted
      mitochondrial biogenesis in Ras-transformed cells, but not in normal epithelia.
      NAC also blocked stromal induction of MCT4, indicating that NAC effectively
      functions as an "MCT4 inhibitor". Taken together, our data provide new strategies
      for achieving more effective anticancer therapy. We conclude that oncogenes
      enable cancer cells to behave as selfish "metabolic parasites", like foreign
      organisms (bacteria, fungi, viruses). Thus, we should consider treating cancer
      like an infectious disease, with new classes of metabolically targeted
      "antibiotics" to selectively starve cancer cells. Our results provide new support
      for the "seed and soil" hypothesis, which was first proposed in 1889 by the
      English surgeon, Stephen Paget.

PMID- 23860381
TI  - Lead sorption onto acrylamide modified titanium nanocomposite from aqueous media.
AB  - The purpose of this study was to investigate the adsorption of lead (Pb(II)) onto
      acrylamide (AM) doped TiO2 nanocomposites (Ti-AM) using batch techniques for
      evaluation of isothermal and kinetic properties. Chemical, structural and
      textural characteristics of the material were determined by FTIR, XPS, XRD, SEM
      and EDAX analysis. XPS results showed that a change in oxidation state occurred
      due to lead adsorption. The adsorption conditions for the adsorbent were
      optimized by varying several experimental parameters, i.e., contact time, initial
      lead concentration, adsorbent dose, pH, and electrolyte amount of the solution.
      The adsorption data were modeled using both the Langmuir and Freundlich
      isotherms. The maximum adsorption capacity using Langmuir isotherm (qmax) for the
      nanocomposite was found to be 476.19 mg g(-1). Adsorption showed pseudo-second
      order kinetics with a rate constant of 8.7 * 10(-4) and 1.2 * 10(-4) g mg(-1)min(
      1) at 100 and 500 mg L(-1) initial Pb(II) concentrations, respectively.
      Acrylamide concentration in nanocomposite synthesis up to 1 g had greater
      influence on the sorption of lead. The most favorable pH for the adsorption was
      pH 5.5. With increasing concentrations of three electrolytes (NaCl, Na2SO4 and
      Na2CO3) from 0.01 to 1.0 M Pb(II), the lead removal decreases from 76.3 to 32.8
      mg g(-1), from 97.4 to 68.7 mg g(-1), and from 98.8 to 72.5 mg g(-1),
      respectively. Further, the Ti-AM nanocomposite is amenable to efficient
      regeneration by a 0.05 N HCl solution for repeated (up to six cycles) use without
      any significant capacity loss, making this approach very economical. 

PMID- 23860383
TI  - Fine-needle aspiration cytology of breast lesions with spontaneous infarction: a
      five-year study.
AB  - OBJECTIVE: To put forth the cytological features and diagnostic pitfalls of
      spontaneously infarcted breast lesions on fine-needle aspiration cytology (FNAC).
      STUDY DESIGN: We present 19 cases of spontaneously infarcted breast lesions
      encountered on FNAC over a 5-year period. Histological follow-up was correlated
      wherever available. RESULTS: The majority of cases were seen in the second decade
      of life. The smears in all 19 cases were cellular. The cytomorphologic findings
      were scattered dyscohesive cells (n = 16), ghost cells (n = 11) and necrosis (n =
      10). The dyscohesive cells were small and had a normal nuclear cytoplasmic ratio
      with pyknotic nuclei. The presence of viable epithelial cells or stromal
      fragments helped in the diagnosis of the primary breast lesion and was seen in
      all 19 cases. Cytology diagnoses were infarcted fibroadenoma (n = 11), infarcted
      breast lesion (n = 3), Phyllodes tumor (n = 2), papillary lesion (n = 2) and
      infarcted benign breast lesion (n = 1). Histopathology was available in 13 cases,
      12 were concordant and 1 was inadequate for primary diagnosis. CONCLUSION: An
      infarcted breast lesion poses diagnostic difficulties on cytology. It needs to be
      differentiated from inflammatory lesions and malignancy. A cytopathologist should
      be aware of the entity and recognize its cytomorphologic features.

PMID- 23860382
TI  - Oncogenes induce the cancer-associated fibroblast phenotype: metabolic symbiosis
      and "fibroblast addiction" are new therapeutic targets for drug discovery.
AB  - Metabolic coupling, between mitochondria in cancer cells and catabolism in
      stromal fibroblasts, promotes tumor growth, recurrence, metastasis, and predicts
      anticancer drug resistance. Catabolic fibroblasts donate the necessary fuels
      (such as L-lactate, ketones, glutamine, other amino acids, and fatty acids) to
      anabolic cancer cells, to metabolize via their TCA cycle and oxidative
      phosphorylation (OXPHOS). This provides a simple mechanism by which metabolic
      energy and biomass are transferred from the host microenvironment to cancer
      cells. Recently, we showed that catabolic metabolism and "glycolytic
      reprogramming" in the tumor microenvironment are orchestrated by oncogene
      activation and inflammation, which originates in epithelial cancer cells.
      Oncogenes drive the onset of the cancer-associated fibroblast phenotype in
      adjacent normal fibroblasts via paracrine oxidative stress. This oncogene-induced
      transition to malignancy is "mirrored" by a loss of caveolin-1 (Cav-1) and an
      increase in MCT4 in adjacent stromal fibroblasts, functionally reflecting
      catabolic metabolism in the tumor microenvironment. Virtually identical findings
      were obtained using BRCA1-deficient breast and ovarian cancer cells. Thus,
      oncogene activation (RAS, NFkB, TGF-beta) and/or tumor suppressor loss (BRCA1)
      have similar functional effects on adjacent stromal fibroblasts, initiating
      "metabolic symbiosis" and the cancer-associated fibroblast phenotype. New
      therapeutic strategies that metabolically uncouple oxidative cancer cells from
      their glycolytic stroma or modulate oxidative stress could be used to target this
      lethal subtype of cancers. Targeting "fibroblast addiction" in primary and
      metastatic tumor cells may expose a critical Achilles' heel, leading to disease
      regression in both sporadic and familial cancers. 

PMID- 23860384
TI  - Development of a magnetic electrochemical bar code array for point mutation
      detection in the H5N1 neuraminidase gene.
AB  - Since its first official detection in the Guangdong province of China in 1996,
      the highly pathogenic avian influenza virus of H5N1 subtype (HPAI H5N1) has
      reportedly been the cause of outbreaks in birds in more than 60 countries, 24 of
      which were European. The main issue is still to develop effective antiviral
      drugs. In this case, single point mutation in the neuraminidase gene, which
      causes resistance to antiviral drug and is, therefore, subjected to many studies
      including ours, was observed. In this study, we developed magnetic
      electrochemical bar code array for detection of single point mutations
      (mismatches in up to four nucleotides) in H5N1 neuraminidase gene. Paramagnetic
      particles Dynabeads(r) with covalently bound oligo (dT)25 were used as a tool for
      isolation of complementary H5N1 chains (H5N1 Zhejin, China and Aichi). For
      detection of H5N1 chains, oligonucleotide chains of lengths of 12 (+5 adenine) or
      28 (+5 adenine) bp labeled with quantum dots (CdS, ZnS and/or PbS) were used.
      Individual probes hybridized to target molecules specifically with efficiency
      higher than 60%. The obtained signals identified mutations present in the
      sequence. Suggested experimental procedure allows obtaining further information
      from the redox signals of nucleic acids. Moreover, the used biosensor exhibits
      sequence specificity and low limits of detection of subnanogram quantities of
      target nucleic acids.

PMID- 23860386
TI  - Nucleated red blood cell counts: an early predictor of brain injury and 2-year
      outcome in neonates with hypoxic-ischemic encephalopathy in the era of cooling
      based treatment.
AB  - BACKGROUND: Raised nucleated red blood cell (NRBC) counts in neonates may
      indicate in utero hypoxia and brain damage. OBJECTIVE: The study aimed to examine
      the use of NRBC counts as a predictor of brain injury and neurodevelopmental
      outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated under
      current cooling-based strategy. METHODS: Forty-three neonates with asphyxia
      between 2004 and 2010 were retrospectively investigated. Twenty neonates with
      moderate/severe HIE underwent hypothermia (HT), and 23 with mild HIE were treated
      in normothermia (NT). Neonates were divided into groups according to the presence
      of cerebral parenchymal lesions on magnetic resonance imaging (MRI) at 2 weeks
      after birth. All patients were followed-up neurologically for ? 24 months. NRBC
      counts during the first 3 days were compared between groups. RESULTS: Eleven HT
      (HT-N) and 21 NT (NT-N) neonates had normal MRI, and 9 HT (HT-L) and 2 NT (NT-L)
      neonates had parenchymal lesions. NRBC counts, both absolute and /100 white blood
      cells (WBC) counts, during the first 3 days in HT-L and NT-L were significantly
      higher than those in HT-N and NT-N, particularly within 6 hours after birth (HT
      N: 502 [0-3060]/mm(3) vs HT-L: 2765 [496-6192]; 0 [0-3417] vs NT-L: 4384 [3978
      4789], median [range]). Neonates with /100 white blood cells ? 6/mm(3) and
      absolute NRBC counts ? 1324/mm(3) within 6 hours of birth had high risks of
      abnormal MRIs and 2-year outcomes. CONCLUSIONS: NRBC counts can predict brain
      injury and neurological outcomes in cooled and non-cooled asphyxiated neonates.

PMID- 23860385
TI  - Role of polycomb proteins in regulating HSV-1 latency.
AB  - Herpes simplex virus (HSV) establishes a latent infection within sensory neurons
      of humans. Latency is characterized by the transcriptional repression of lytic
      genes by the condensation of lytic gene regions into heterochromatin. Recent data
      suggest that facultative heterochromatin predominates, and that cellular Polycomb
      proteins are involved in the establishment and maintenance of transcriptional
      repression during latency. This review summarizes these data and discusses the
      implication of viral and cellular factors in regulating heterochromatin
      composition. 

PMID- 23860387
TI  - Calorie restriction and resveratrol supplementation prevent age-related DNA and
      RNA oxidative damage in a non-human primate.
AB  - Oxidative stress is a key factor in the aging process and in the development of
      age-related diseases. Because nutritional interventions such as caloric
      restriction (CR) delay the onset of age-related diseases and increase the
      lifespan of many species, the impact of a moderate CR was tested on male grey
      mouse lemur (Microcebus murinus), which have a median survival time of 5.7 years
      in captivity. The effects of CR on these lemurs were compared with a potential
      mimetic, resveratrol (RSV), a polyphenol naturally found in grapes. We
      hypothesized that both CR and RSV impact oxidative DNA and RNA damage compared to
      standard-fed control (CTL) animals. Adult (3-4 years old) male mouse lemurs were
      assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer
      calories than the CTL and a RSV group receiving the CTL diet supplemented with
      RSV (200 mg.day(-1).kg(-1)). Oxidative stress was estimated after 3, 9, 15 and 21
      months of treatment using the measurement of oxidized nucleosides in urine
      samples by mass spectrometry. The resting metabolic rate, adjusted for changes in
      body composition, was also measured to assess the potential relationship between
      oxygen consumption and oxidative damage markers. This study provides evidence for
      oxidative stress accumulation with age in grey mouse lemur. Dietary interventions
      resulted in a short-term increase in oxidative stress levels followed by reduced
      levels with increasing age. Moreover, in this photoperiod-dependent heterotherm
      primate, seasonal variations in oxidative stress were observed, which was likely
      due to a season-dependent, cost-benefit trade-off between torpor use and
      oxidative stress.

PMID- 23860388
TI  - Chicken MDA5 senses short double-stranded RNA with implications for antiviral
      response against avian influenza viruses in chicken.
AB  - Mammalian melanoma differentiation-associated gene-5 (MDA5) and retinoic acid
      inducible gene-I (RIG-I) selectively sense double-stranded RNA (dsRNA) according
      to length, as well as various RNA viruses to induce an antiviral response. RIG-I,
      which plays a predominant role in the induction of antiviral responses against
      influenza virus infection, has been considered to be lacking in chicken, putting
      the function of chicken MDA5 (chMDA5) under the spotlight. Here, we show that
      chMDA5, unlike mammalian MDA5, preferentially senses shorter dsRNA synthetic
      analogues, poly(I:C), in chicken DF-1 fibroblasts. A requirement for caspase
      activation and recruitment domains for chMDA5-mediated chicken interferon beta
      (chIFNbeta) induction and its interaction with mitochondrial antiviral signaling
      proteins were demonstrated. We also found that chMDA5 is involved in chIFNbeta
      induction against avian influenza virus infection. Our findings imply that chMDA5
      compensates in part the function of RIG-I in chicken, and highlights the
      importance of chMDA5 in the innate immune response in chicken.

PMID- 23860389
TI  - Prevalence of dementia in Japan: a systematic review.
AB  - BACKGROUND/AIMS: The actual prevalence of dementia in Japan as well as the
      changes in the prevalence are not well known. Therefore, we undertook a
      systematic review to collect evidence regarding the prevalence of dementia in
      Japan. METHODS: For this systematic review, we searched 2 electronic databases to
      identify cross-sectional or repeated cross-sectional studies with data regarding
      the study population, study location, diagnostic criteria, and prevalence of
      dementia. RESULTS: Twenty-one studies were selected from 782 references. Sixteen
      studies surveyed individuals living at home; of these, 5 studies also included
      hospitalized or institutionalized patients. Most of the studies were conducted
      using a two-phase survey (phase I: screening, phase II: diagnosis of dementia).
      The clinical diagnosis of dementia was made based on the guidelines of the
      Diagnostic and Statistical Manual of Mental Disorders (DSM) in a majority of the
      studies. The prevalence of all types of dementia ranged from 2.9 to 12.5% and has
      been gradually increasing over the past few years. CONCLUSION: The results of
      this systematic review suggest that the prevalence of dementia has recently
      increased. However, further well-designed studies taking into account factors
      that affect the prevalence of dementia are needed to clarify the actual
      prevalence.

PMID- 23860390
TI  - Team Physician Consensus Statement: 2013 update.

PMID- 23860391
TI  - Doppler ultrasound and X-ray-guided percutaneous nephrolithotomy with one-step
      balloon dilation for complex renal stones.
AB  - OBJECTIVES: To assess the safety and efficacy of combining Doppler ultrasound
      with X-ray-guided percutaneous nephrolithotomy (PCNL) with one-step balloon
      dilation for management of complex renal stones. MATERIAL AND METHODS: We
      retrospectively analyzed 85 renal stone patients who underwent 89 PCNLs from
      January 2011 to May 2012. Doppler ultrasound with X-ray-guided PCNL with one-step
      balloon dilation was finished on the Fluoroscopic Table (Siemens, Berlin,
      Germany) with the patient under general anesthesia. RESULTS: The study included
      85 patients (49 male and 36 female) with a mean age of 42.5 +/- 16.4 years. All
      patients underwent 89 PCNLs (4 patients had bilateral stones). The mean operative
      time was 72.8 min (range: 35-140). The average fluoroscopic screening time was
      5.55 +/- 1.81 s (range: 4-12). Successful access to the collecting system was
      98.9% (88/89). Although most of the cases (85/89) were managed satisfactorily by
      a single tract, a second tract was used in 4 cases. No severe complications
      occurred. The stone-free rate of PCNL monotherapy was 77.5% (69/89). At 3 months,
      the stone-free rate increased to 89.9% (80/89) after shock wave lithotripsy.
      CONCLUSIONS: PCNL with one-step balloon dilation for the management of complex
      renal stones under the guidance of combining Doppler ultrasound with X-ray is
      safe and effective because of its high stone-free rate and low operative time.

PMID- 23860392
TI  - Breast lesion co-localisation between X-ray and MR images using finite element
      modelling.
AB  - This paper presents a novel X-ray and MR image registration technique based on
      individual-specific biomechanical finite element (FE) models of the breasts.
      Information from 3D magnetic resonance (MR) images was registered to X-ray
      mammographic images using non-linear FE models subject to contact mechanics
      constraints to simulate the large compressive deformations between the two
      imaging modalities. A physics-based perspective ray-casting algorithm was used to
      generate 2D pseudo-X-ray projections of the FE-warped 3D MR images. Unknown input
      parameters to the FE models, such as the location and orientation of the
      compression plates, were optimised to provide the best match between the pseudo
      and clinical X-ray images. The methods were validated using images taken before
      and during compression of a breast-shaped phantom, for which 12 inclusions were
      tracked between imaging modalities. These methods were then applied to X-ray and
      MR images from six breast cancer patients. Error measures (such as centroid and
      surface distances) of segmented tumours in simulated and actual X-ray mammograms
      were used to assess the accuracy of the methods. Sensitivity analysis of the
      lesion co-localisation accuracy to rotation about the anterior-posterior axis was
      then performed. For 10 of the 12 X-ray mammograms, lesion localisation accuracies
      of 14 mm and less were achieved. This analysis on the rotation about the anterior
      posterior axis indicated that, in cases where the lesion lies in the plane
      parallel to the mammographic compression plates, that cuts through the nipple,
      such rotations have relatively minor effects.This has important implications for
      clinical applicability of this multi-modality lesion registration technique,
      which will aid in the diagnosis and treatment of breast cancer.

PMID- 23860393
TI  - Symptom occurrence and severity on the therapy-related symptom checklist for
      children among Hispanic pediatric oncology outpatients.
AB  - BACKGROUND: A calibrated easy-to-use symptom checklist for children who are under
      treatment for cancer had been developed and reported in Cancer Nursing. The 30
      item Therapy-Related Symptom Checklist for Children (TRSC-C) has good measurement
      and psychometric properties and uses "kid-friendly" terms to monitor symptom
      occurrence and severity during oncology treatment. A secondary analysis is
      reported using participants who self-identified as Hispanic. OBJECTIVE: The
      objective of this study was to examine among Hispanic pediatric oncology
      outpatients (a) occurrence and (b) severity of symptoms reported on the TRSC-C,
      (c) relationships of symptoms to gender and age (<12 vs >=12), and (d)
      differences in summated TRSC-C symptom scores between patients with acute
      lymphoblastic leukemia (ALL) and other diagnoses. METHOD: This was a cross
      sectional analysis using secondary data and descriptive statistics. SAMPLE: The
      sample was composed of 79 children (55% male) aged 5 to 17 years (mean, 10.3
      years) with diagnosis of ALL (52%) or other (48%). Instrument used was TRSC-C by
      patient/parent report (Cronbach's alpha = .91). RESULTS: (a) Symptom occurrence:
      15 symptoms on the TRSC-C were reported by 40% or greater. (b) Severity means on
      11 symptoms were greater than "a little bit." (c) No gender or age differences
      were found on mean TRSC-C summated scores. (d) Mean TRSC-C scores (symptom
      occurrence and severity) were slightly lower but not significantly different (t =
      1.71) between ALL (13.71 [SD, 8.06]) and other diagnoses (15.71 [SD, 7.01]).
      CONCLUSION: Symptom occurrence and severity reported on the TRSC-C by this
      Hispanic subsample are consistent with findings in the calibration study and with
      those of another Hispanic group and other ethnicities. IMPLICATIONS FOR PRACTICE:
      Use of the TRSC-C is appropriate during pediatric oncology treatment and
      diagnoses of Hispanic populations.

PMID- 23860394
TI  - Translation and linguistic validation of the Pediatric Patient-Reported Outcomes
      Measurement Information System measures into simplified Chinese using cognitive
      interviewing methodology.
AB  - BACKGROUND: The Pediatric Patient-Reported Outcomes Measurement Information
      System (PROMIS) measures were developed using modern measurement theory and
      tested in a variety of settings to assess the quality of life, function, and
      symptoms of children and adolescents experiencing a chronic illness and its
      treatment. Developed in English, this set of measures had not been translated
      into Chinese. OBJECTIVE: The objective of this study was to develop the Chinese
      version of the Pediatric PROMIS measures (C-Ped-PROMIS), specifically 8 short
      forms, and to pretest the translated measures in children and adolescents through
      cognitive interviewing methodology. METHODS: The C-Ped-PROMIS was developed
      following the standard Functional Assessment of Chronic Illness Therapy
      Translation Methodology. Bilingual teams from the United States and China
      reviewed the translation to develop a provisional version, which was then
      pretested with cognitive interview by probing 10 native Chinese-speaking children
      aged 8 to 17 years in China. RESULTS: The translation was finalized by the
      bilingual teams. Most items, response options, and instructions were well
      understood by the children, and some revisions were made to address patient's
      comments during the cognitive interview. CONCLUSIONS: The results indicated that
      the C-Ped-PROMIS items were semantically and conceptually equivalent to the
      original. Children aged 8 to 17 years in China were able to comprehend these
      measures and express their experience and feelings about illness or their life.
      IMPLICATIONS FOR PRACTICE: The C-Ped-PROMIS is available for psychometric
      validation. Future work will be directed at translating the rest of the item
      banks, calibrating them and creating a Chinese final version of the short forms.

PMID- 23860395
TI  - Participating in life again: a mixed-method study on a goal-orientated
      rehabilitation program for young adult cancer survivors.
AB  - BACKGROUND: Young adult cancer survivors (18-35 years old) are at risk of
      lifelong threats to physical and psychosocial health and decreased life
      participation. Research indicates lack of information about the late effects and
      health risks and limited follow-up and rehabilitation. OBJECTIVE: The objectives
      of this study were to examine whether a goal-oriented rehabilitation program
      increased young adult cancer survivors' participation and explore the
      participants' descriptions and experience of the process. METHODS: We used a
      convergent parallel design combining quantitative and qualitative methods.
      Sixteen young adult cancer survivors (aged 24-35 years), with different cancer
      diagnoses, were allocated to a 6-month rehabilitation program. RESULTS: The
      Canadian Occupational Performance Measure showed significant (P < .001) change in
      both performance and satisfaction from the start (T1) to the end (T4) of the
      program. Qualitative results indicated that increased participation was depended
      on building capacity and finding the balance, gaining new insight, and follow-up.
      Important factors of the rehabilitation program seemed to be physical activity,
      psychoeducation, peer-to-peer support, and follow-up over time. CONCLUSIONS:
      Results indicate that a goal-oriented rehabilitation program may increase
      participation by young adult cancer survivors. The goal-oriented process is not
      straightforward and depends on experience of coping and control, finding a
      balance between the different areas of life and follow-up over time. IMPLICATIONS
      FOR PRACTICE: Health professionals should play an important role in the
      rehabilitation of young adult cancer survivors by promoting empowerment and
      follow-up over time. The Canadian Occupational Performance Measure seems to be a
      valuable instrument for setting goals and thus helps facilitate participation.

PMID- 23860396
TI  - Sequential effects of spadetail, one-eyed pinhead and no tail on midline
      convergence of nephric primordia during zebrafish embryogenesis.
AB  - Midline convergence of organ primordia is an important mechanism that shapes the
      vertebrate body plan. Here, we focus on the morphogenetic movements of pronephric
      glomerular primordia (PGP) occurring during zebrafish embryonic kidney
      development. To characterize the process of PGP midline convergence, we used
      Wilms' tumour 1a (wt1a) as a marker to label kidney primordia, and performed
      quantitative analyses of the migration of the bilateral PGP. The PGP initially
      are approximately 350 MUm apart in a wild type embryo at 10h post fertilization
      (hpf). The inter-PGP distance decreases exponentially between 10 and 48 hpf,
      while the anterior-posterior (A-P) dimension of each PGP increases linearly
      between 10 and 12 hpf, then decreases substantially between 12 and 24 hpf. Using
      mutants in the Nodal receptor cofactor one-eyed pinhead (oep) and the T-box
      transcription factors spadetail (spt) and no tail (ntl), we were able to define
      distinctive regulation underlying these sequential phases of PGP midline
      migration. Zygotic oep mutants (Zoep(-/-)) exhibited defects in midline
      convergence after 16 hpf. Spt is necessary for PGP convergence from 10 hpf,
      whereas ntl's effect on convergence does not begin until 24 hpf. Notably, we
      observed normal cardiac convergence in spt(-/-) and ntl(-/-) embryos implying
      that these novel roles of spt and ntl in PGP migration cannot be explained simply
      by generalised effects on midline convergence. These findings demonstrate that
      quantitative approaches to developmental migration allow the parsing of early
      patterning events, and in this instance suggest that the zebrafish may offer
      insights into midline urogenital migration anomalies in humans.

PMID- 23860397
TI  - Association between infection of virulence cagA gene Helicobacter pylori and
      laryngeal squamous cell carcinoma.
AB  - BACKGROUND: The aim of the study was to evaluate the presence of cagA gene
      Helicobacter pylori in etiopathogenesis of initiation and development of larynx
      squamous cell carcinoma (LSCC) and its predictable role as a prognostic factor.
      MATERIAL AND METHODS: The prospective, controlled study involved a series of 75
      patients (65 male, 10 female, mean age 59.1 years, range 43 to 79 years) with
      larynx cancer. Samples of larynx cancerous tissue, each of 10-15 mg, were
      obtained from fresh tissues and were used for nucleic acid purification. DNA was
      extracted from 225 samples (larynx tumor - I (75), margin of tumor and normal
      tissue - II (75) and normal larynx tissue from opposite side to the tumor - III).
      All samples were subjected to H. pylori ureA detection by the PCR H. pylori
      diagnostic test. Samples that were positive for ureA H. pylori gene were
      evaluated for cagA H. pylori gene. RESULTS: Presence of H. pylori cagA gene was
      identified in 46,7% to 49,3% of 75 H. pylori ureA gene-positive larynx cancer
      depending of tissue location. There was a correlation of high incidence of
      positive cagA gene in larynx cancer tissue in supraglottic versus subglottic and
      glottic location. We observed a predominance of cagA gene in LSCC in patients
      with positive cervical lymph nodes and clinical stage T3 and T4. CONCLUSIONS: H.
      pylori is present in larynx tissue and may be a possible carcinogen or co
      carcinogen in LSCC development, but that must be addressed by future
      investigations. The presence of cagA gene in larynx cancer tissues significantly
      decreases survival rate and increases the disease recurrence possibilities.

PMID- 23860398
TI  - Point defect-grain boundary interactions in MgO: an atomistic study.
AB  - The way in which point defects interact with grain boundaries in oxides is
      important for understanding radiation damage evolution, sintering, and many other
      technologically important applications. Here, we examine how vacancies interact
      with three different grain boundaries in MgO, chosen as a model oxide ceramic.
      Further, we compare the vacancy interaction with both pristine (as constructed)
      and 'damaged' boundaries, in which excess interstitials are placed in the
      boundary plane to mimic the structure after a damage event. We find that the
      excess interstitials significantly change the interaction of the vacancies with
      the boundaries and that this change is sensitive to the atomic structure of the
      boundary. We further observe that complex electrostatic effects arise that can
      dominate the interaction. These results show that, as boundaries absorb defects,
      their interaction with other defects will change dramatically. 

PMID- 23860399
TI  - Airborne manufactured nano-objects released from commercially available spray
      products: temporal and spatial influences.
AB  - This paper reports a study of the dispersion of manufactured nano-objects (MNOs)
      through the air, both in time and space, during the use of two commercially
      available nano-spray products and comparable products without MNOs. The main
      objective was to identify whether personal exposure can occur at a greater
      distance than the immediate proximity of the source (>1 m from the source), that
      is, in the "far field" (bystanders), or at a period after the emission occurred
      (re-entry). The spray experiments were conducted in an experimental room with
      well-controlled environmental and ventilation conditions (19.5 m(3)). The
      concentration of MNOs was investigated by measuring real-time size distribution,
      number, and active surface area concentration. For off-line analysis of the
      particles in the air, samples for scanning/transmission electron microscopy and
      elemental analysis were collected. The release of MNOs was measured at ~30 and
      290 cm from the source ("near field" and "far field", respectively). For all four
      spray products, the maximum number and surface area concentrations in the "near
      field" exceeded the maximum concentrations reached in the "far field". At 2 min
      after the emission occurred, the concentration in both the "near field" and "far
      field" reached a comparable steady-state level above background level. These
      steady-state concentrations remained elevated above background concentration
      throughout the entire measurement period (12 min). The results of the real-time
      measurement devices mainly reflect the liquid aerosols emitted by the spray
      process itself rather than only the MNO, which hampers the interpretation of the
      results. However, the combination of the off-line analysis and the results of the
      real-time devices indicates that after the use of nano-spray products, personal
      exposure to MNOs can occur not only in the near field, but also at a greater
      distance than the immediate proximity of the source and at a period after
      emission occurred. 

PMID- 23860401
TI  - Simulating real-world exposures during emergency events: studying effects of
      indoor and outdoor releases in the Urban Dispersion Program in upper Manhattan,
      NY.
AB  - A prospective personal exposure study, involving indoor and outdoor releases, was
      conducted in upper Midtown Manhattan in New York City as part of the Urban
      Dispersion Program (UDP) focusing on atmospheric dispersion of chemicals in
      complex urban settings. The UDP experiments involved releases of very low levels
      of perfluorocarbon tracers (PFTs) in Midtown Manhattan at separate locations,
      during two seasons in 2005. The study presented here includes both outdoor and
      indoor releases of the tracers, and realistic scripted activities for
      characterizing near source and neighborhood-scale exposures using 1-min and 10
      min duration samples, respectively. Results showed that distributions of
      individual tracers and exposures to them within the study area were significantly
      influenced by surface winds, urban terrain, and movements of people typical of
      urban centers. Although in general, PFT levels returned quickly to zero in
      general after cessation of the emissions, in some cases, the concentrations
      stayed at higher levels after the releases stopped. This is likely due to
      accumulation of the PFTs in some buildings, which then serve as "secondary
      sources" when outside levels are lower than indoor levels. Measurements of
      neighborhood-scale PFT concentrations (up to distances of several blocks away
      from the release points) provided information needed to establish a baseline for
      determining how different types of releases could affect exposures both to the
      general public and to emergency responders. These data highlight the factors
      impacting the toxic threat levels following releases of hazardous chemicals and
      provide supporting information for evaluating and refining protocols for
      emergency event response. 

PMID- 23860400
TI  - Contribution of diet to aggregate arsenic exposures-an analysis across
      populations.
AB  - The relative contribution of dietary arsenic (As) to aggregate daily exposure has
      not been well-characterized, especially in relation to the current EPA maximum
      contaminant level (MCL) of 10 p.p.b. for As in drinking water. Our objectives
      were to: (1) model exposure to inorganic and total As among non-seafood eaters
      using subject-specific data, (2) compare the contribution of food, drinking and
      cooking water to estimated aggregate exposure in households with variable
      background tap water As levels, and (3) describe the upper distribution of
      potential dose at different thresholds of tap water As. Dietary As intake was
      modeled in regional study populations and NHANES 2003-2004 using dietary records
      in conjunction with published food As residue data. Water As was measured in the
      regional studies. Among subjects exposed to tap water As >10 p.p.b., aggregate
      inorganic exposure was 24.5-26.1 MUg/day, with approximately 30% of intake from
      food. Among subjects living in homes with tap water As <=10, 5 or 3 p.p.b.,
      aggregate inorganic As exposure was 8.6-11.8 MUg/day, with 54-85% of intake from
      food. Median inorganic As potential dose was 0.42-0.50 MUg/kg BW/day in subjects
      exposed to tap water As >10 p.p.b. and less than half that among subjects exposed
      to tap water As <=10 p.p.b. The majority of inorganic and total As exposure is
      attributable to diet in subjects with tap water As <MCL. Further research is
      needed to determine the potential toxicity and need for regulation of As in
      foods. 

PMID- 23860402
TI  - Green synthesis of silver nanoparticles from Gloriosa superba L. leaf extract and
      their catalytic activity.
AB  - The present work focuses the use of aqueous extract of Gloriosa superba Linn.
      (Glory Lily) for producing silver nanoparticles (AgNPs) from silver nitrate
      aqueous solution. Phytochemical analysis of the extract revealed the presence of
      alkaloid, amino acids, carbohydrates and proteins in the extract and they serve
      as effective reducing and capping agents for converting silver nitrate to silver
      nanoparticles. The nanoparticles were characterised by UV (Ultra violet), FT-IR
      (Fourier Transform Infrared), XRD (X-ray diffraction), TEM (Transmission Electron
      Microscope) SEM-EDX (Scanning Electron Microscopy-Energy Dispersive X-ray), and
      PL (Photoluminescence) studies. Moreover, the catalytic activity of synthesized
      AgNPs in the reduction of methylene blue was studied by UV-vis spectrophotometer.
      The synthesized AgNPs are observed to have a good catalytic activity on the
      reduction of methylene blue by G. superba extract which is confirmed by the
      decrease in absorbance maximum values of methylene blue with respect to time
      using UV-vis spectrophotometer. 

PMID- 23860403
TI  - A 4-(o-chlorophenyl)-2-aminothiazole: microwave assisted synthesis, spectral,
      thermal, XRD and biological studies.
AB  - A 4-(o-chlorophenyl)-2-aminothiazole (CPAT) has been synthesized by reacting o
      chloroacetophenone, iodine and thiourea under microwave irradiation as a green
      chemistry approach. The reactions proceed selectively and within a couple of
      minutes giving high yields of the products. The compound was characterized by
      elemental, spectral (UV-visible, IR, NMR and GC-MS), XRD and thermal analyses.
      The TG curve of the compound was analyzed to calculate various kinetic parameters
      (n, E, Z, DeltaS and DeltaG) by using Coats-Redfern (C.R.), MacCallum-Tanner
      (M.T.) and Horowitz-Metzger (H.M.) method. The compound was tested for the
      evaluation of antibacterial activity against B. subtilis and E. coli and
      antifungal activity against A. niger and C. albicans. The compound was evaluated
      for their in vitro nematicidal activity on plant parasitic nematode Meloidogyne
      javanica and molluscicidal activity on fresh water helminthiasis vector snail
      Lymnea auricularia. The compound is biologically active in very low
      concentration. X-ray diffraction study suggests a triclinic crystal system for
      the compound. 

PMID- 23860404
TI  - Binary and ternary copper(II) complexes of a tridentate ONS ligand derived from 2
      aminochromone-3 carboxaldehyde and thiosemicarbazide: synthesis, spectral studies
      and antimicrobial activity.
AB  - A tridentate ONS donor ligand, HL, was synthesized by the condensation of 2
      aminochromone-3-carboxaldehyde with thiosemicarbazide. The structure of the
      ligand was elucidated by elemental analyses, IR, (1)H and (13)C NMR, electronic
      and mass spectra. Reaction of the ligand with several copper(II) salts, including
      AcO(-), NO3(-), SO4(2-), Cl(-), Br(-) and ClO4(-) afforded different metal
      complexes that reflect the non-coordinating or weakly coordinating power of the
      ClO4(-) and Br(-) anions as compared to the strongly coordinating power of AcO(
      ), SO4(2-), Cl(-) and NO3(-) anions. Also, the ligand was allowed to react with
      Cu(II) ion in the presence of a secondary ligand (L') [N,O-donor; 8
      hydroxyquinoline or N,N-donor; 1,10-phenanthroline]. Characterization and
      structure elucidation of the prepared complexes were achieved by elemental and
      thermal analyses, IR, electronic, mass and EPR spectra as well as conductivity
      and magnetic susceptibility measurements. The EPR spin Hamiltonian parameters of
      some complexes were calculated. The metal complexes exhibited octahedral and
      square planar geometrical arrangements depending on the nature of the anion. The
      ligand and most of its metal complexes showed antibacterial activity towards Gram
      positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative
      bacteria (Salmonella typhimurium and Escherichia coli), yeast (Candida albicans)
      and fungus (Aspergillus fumigatus). 

PMID- 23860405
TI  - Endothelial cell activation and proliferation modulate NKG2D activity by
      regulating MICA expression and shedding.
AB  - MICA are major histocompatibility complex class I-related molecules, expressed by
      endothelial cells (ECs), that may be targets for alloantibodies and NKG2D
      expressing natural killer (NK) and T effector cells in organ allografts. This
      study shows that basal levels of MICA expressed on vascular ECs is sufficient to
      functionally modulate the expression and activity of the immunoreceptor NKG2D in
      allogeneic NK cells. We found that MICA expression is differentially regulated at
      the EC surface in response to cytokines. TNFalpha upregulates MICA while IFNgamma
      significantly decreases MICA at the EC surface. Both cytokines induce the release
      of soluble MICA by ECs. Modulation of NKG2D correlates with the MICA level on the
      EC surface. Glycosylation and metalloproteinase activities account for major post
      transcriptional mechanisms controlling MICA level and the function in ECs. Our
      results indicate that, in addition to the NFkappaB pathway, the mitogen-activated
      protein kinase pathways JNK, ERK1/2 and p38 are key signaling pathways in the
      control of MICA by the cytokines. Finally, we show that EC proliferation mediated
      by FGF-2 or wound healing increases the MICA level. Together, our data suggest
      that inflammation and proliferation regulate endothelial MICA expression and
      shedding, enabling ECs to modulate NKG2D activity on effector NK and T cells, and
      provide further evidence of a role for ECs in immunoregulation.

PMID- 23860406
TI  - Increased anxiety induced by listening to unpleasant music during stress exposure
      is associated with reduced blood pressure and ACTH responses in healthy men.
AB  - The relationship between anxiety and the neuroendocrine response to stress
      stimuli is still not fully understood. The aim of this study was to evaluate the
      contribution of an acute increase in state anxiety to neuroendocrine activation
      under stress conditions. To do so, it was necessary to find a stress condition of
      the same character and intensity with and without a rise in state anxiety. We
      decided to examine the effects of listening to music on anxiety and to apply a
      new methodological approach. A group of 14 healthy volunteers participated in a
      counterbalanced crossover design study. The stress procedure consisted of mental
      (Stroop test, mental arithmetic) and physical (handgrip exercise) tasks combined
      with listening to music played forward (pleasant) or backwards (unpleasant). The
      results confirmed our hypothesis, namely the condition with listening to
      unpleasant music was anxiogenic, while the other was not. In case of increased
      state anxiety, the rise in ACTH concentrations in response to mental challenge
      and the increase in systolic blood pressure induced by handgrip exercise was
      reduced compared to the situation with unchanged anxiety. Concentrations of
      testosterone, oxytocin, vasopressin and aldosterone were slightly increased in
      response to the stress paradigm accompanied with increased anxiety. In
      conclusion, the present data demonstrate that an acute increase in state anxiety
      contributes to neuroendocrine activation under stress conditions. Moreover, the
      results show that listening to music may both positively and negatively influence
      the perception of stress and the level of anxiety, which might have functional
      consequences. 

PMID- 23860407
TI  - Adenocarcinoma of the lung with scattered consolidation: radiological
      pathological correlation and prognosis.
AB  - PURPOSE: To investigate the clinicopathological features and prognosis in
      patients with adenocarcinoma of the lung with scattered consolidation (ALSC).
      MATERIALS AND METHODS: Between January 2006 and March 2010, 139 consecutive
      patients with lung adenocarcinoma of <=3 cm, who underwent pulmonary resection
      for lung cancer, were investigated retrospectively. Radiologic classification was
      based on the findings of thin-section CT such as the presence of consolidation or
      ground-glass opacity (GGO). Type I (n=15) and Type II (n=14), showed a pure GGO
      and a mixed GGO with consolidation <50%, respectively. Type IV (n=38) and Type V
      (n=52) showed a mixed GGO with consolidation >=50% and a pure consolidation,
      respectively. Type III (n=20) was the adenocarcinoma of the lung with scattered
      consolidation (ALSC). The clinicopathological features and prognosis of ALSC was
      investigated with comparative analysis and survival analysis. RESULTS: Because of
      the similar recurrence rate for Type I and Type II (P=1.000), Type IV and Type V
      (P=0.343), we merged Type I and Type II as Type I+II, Type IV and Type V as Type
      IV+V, respectively. In the 20 (14.4%) patients with ALSC, lymph node metastasis
      was not observed, and it was rare in lymphatic invasion and vascular invasion. On
      the basis of IASLC/ATS/ERS 2011 classification, 80% of the ALSC were preinvasive
      lesions. In Noguchi classification, there was no significant difference between
      Type I+II and ALSC (P=0.260). The prognosis of ALSC was similar to Type I+II
      (P=0.408), but better than Type IV+V (P=0.040). CONCLUSION: Adenocarcinoma of the
      lung with scattered consolidation (ALSC) on thin-section CT was a relatively
      favorable prognostic factor.

PMID- 23860408
TI  - Key concepts behind forming-free resistive switching incorporated with rectifying
      transport properties.
AB  - This work reports the effect of Ti diffusion on the bipolar resistive switching
      in Au/BiFeO3/Pt/Ti capacitor-like structures. Polycrystalline BiFeO3 thin films
      are deposited by pulsed laser deposition at different temperatures on
      Pt/Ti/SiO2/Si substrates. From the energy filtered transmission electron
      microscopy and Rutherford backscattering spectrometry it is observed that Ti
      diffusion occurs if the deposition temperature is above 600 degrees C. The
      current-voltage (I-V) curves indicate that resistive switching can only be
      achieved in Au/BiFeO3/Pt/Ti capacitor-like structures where this Ti diffusion
      occurs. The effect of Ti diffusion is confirmed by the BiFeO3 thin films
      deposited on Pt/sapphire and Pt/Ti/sapphire substrates. The resistive switching
      needs no electroforming process, and is incorporated with rectifying properties
      which is potentially useful to suppress the sneak current in a crossbar
      architecture. Those specific features open a promising alternative concept for
      nonvolatile memory devices as well as for other memristive devices like synapses
      in neuromorphic circuits. 

PMID- 23860409
TI  - Revealing the anti-tumoral effect of Algerian Glaucium flavum roots against human
      cancer cells.
AB  - Glaucium flavum (G. flavum) is a plant from the Papaveraceae family native to
      Algeria where it is used in local traditional medicine to treat warts. G. flavum
      root crude alkaloid extract inhibited breast cancer cell proliferation and
      induced G2/M phase cycle arrest and apoptosis without affecting normal cells,
      which is a highly awaited feature of potential anti-cancer agents. G. flavum
      significantly reduced growth and vascularization of human glioma tumors on
      chicken chorioallantoic membrane (CAM) in vivo. The chromatographic profile of
      the dichloromethane extract of G. flavum root showed the presence of different
      constituents including the isoquinoline alkaloid protopine, as the major
      compound. We report for the first time that G. flavum extract may represent a new
      promising agent for cancer chemotherapy. 

PMID- 23860410
TI  - Notch signaling downregulates MUC5AC expression in airway epithelial cells
      through Hes1-dependent mechanisms.
AB  - BACKGROUND: Mucus overproduction is one of the major pathological features of
      asthma, and MUC5AC is the major mucin component of airway mucus. However, whether
      Notch signaling is implicated in the regulation of MUC5AC expression in airway
      secretary cells is still undetermined. OBJECTIVE: The aim of this study is to
      examine whether Notch signaling can regulate MUC5AC expression and explore the
      molecular mechanisms. METHODS: Mouse mtCC1-2 cells and human NCI-H292 cells were
      transfected with NIC, and MUC5AC expression was examined. Using gene reporter
      assays, site-directed mutagenesis, and ChIP assays, the activity of both mouse
      and human MUC5AC promoter was analyzed. RESULTS: Notch signaling regulated MUC5AC
      expression both in mouse mtCC1-2 cells and in human NCI-H292 cells. Several Hes
      binding site N-boxes were identified in the 5' region of both mouse and human
      MUC5AC promoters. Overexpression of NIC resulted in activation of the MUC5AC
      promoter. Site-directed mutagenesis report assays revealed that Hes proteins
      might repress both mouse and human MUC5AC promoter activity. Furthermore, ChIP
      assays confirmed that Hes1 binds to the MUC5AC promoter both in mouse mtCC1-2
      cells and in human NCI-H292 cells. CONCLUSIONS: Notch signaling can directly
      downregulate MUC5AC promoter activity through Hes1-dependent mechanisms, which
      may be identified as possible targets for pharmacotherapy of airway mucus
      hypersecretion in asthma.

PMID- 23860411
TI  - Metastatic renal cell carcinoma to the pancreas: diagnostic significance of fine
      needle aspiration cytology.
AB  - BACKGROUND: Renal cell carcinoma rarely metastasizes to the pancreas. Diagnosing
      a neoplasm that is metastatic to the pancreas by fine-needle aspiration (FNA)
      cytology is often challenging. A detailed clinical history may prove to be
      beneficial. CASE REPORTS: A total of 729 pancreatic FNAs were performed from
      January 2005 through August 2012 at our institution. Among these, we found 3
      patients with a prior history of a malignant renal neoplasm who presented with a
      pancreatic mass: 2 in the tail and 1 in the head. Radiographically, they ranged
      in size from 2.5 to 7.0 cm. Microscopic evaluation of cytologic material obtained
      during endoscopic ultrasound-guided FNA (EUS-FNA) revealed cohesive clusters of
      atypical cells with clear cytoplasm and prominent nucleoli surrounded by a thin
      capillary network. The neoplastic cells were immunoreactive with CD10 (cases 2
      and 3). A diagnosis of metastatic clear cell renal cell carcinoma was rendered
      for each case based on the morphologic features and immunohistochemical staining
      pattern of the neoplastic cells. Histologic comparison with the available slides
      of the corresponding primary renal neoplasm confirmed the diagnosis. CONCLUSION:
      We conclude that EUS-FNA of pancreatic masses is an important, effective, and
      accurate diagnostic modality for early diagnosis of both primary and metastatic
      neoplasms of the pancreas.

PMID- 23860412
TI  - Frequent nocturnal hemodialysis associates with improvement of prolonged QTc
      intervals.
AB  - BACKGROUND/AIMS: Sudden cardiac death remains the leading cause of death in
      hemodialysis (HD) patients. Prolongation of QTc intervals (as measured by the
      tangent method) increases sudden cardiac death risk in populations without kidney
      disease. METHODS: We performed a retrospective electrocardiograph (ECG) and chart
      review of HD patients. Our objectives were (1) to establish the effect of one of
      four different dialysis modalities on interdialytic QTc intervals, (2) to
      determine the effect of dialysis frequency and time on QTc interval and on the
      prevalence of borderline or prolonged QTc intervals, and (3) to determine if
      changes in QTc interval were simultaneous to changes in electrocardiographic left
      ventricular mass. RESULTS: Frequent nocturnal HD was associated with a decrease
      in QTc interval for all patients (from 436.5 to 421.3 ms, p = 0.0187) and for
      patients who initiated dialysis with prolonged QTc (468.2 to 438.2 ms, p =
      0.0134). This change happened before changes in left ventricular mass were
      evident. Dialysis duration predicted a decrease in QTc better than dialysis
      frequency (R(2) 6.50 vs. 3.00%, p = 0.023 vs. 0.102). Prevalence of borderline or
      prolonged QTc increased in patients dialyzed <4 h/session (12/39 to 22/39, p =
      0.039). CONCLUSIONS: Frequent nocturnal HD may be the ideal modality to initiate
      HD in end-stage kidney disease patients with prolonged QTc.

PMID- 23860413
TI  - Production of hydroxy fatty acids by microbial fatty acid-hydroxylation enzymes.
AB  - Hydroxy fatty acids are widely used in chemical, food, and cosmetic industries as
      starting materials for the synthesis of polymers and as additives for the
      manufacture of lubricants, emulsifiers, and stabilizers. They have antibiotic,
      anti-inflammatory, and anticancer activities and therefore can be applied for
      medicinal uses. Microbial fatty acid-hydroxylation enzymes, including P450,
      lipoxygenase, hydratase, 12-hydroxylase, and diol synthase, synthesize regio
      specific hydroxy fatty acids. In this article, microbial fatty acid-hydroxylation
      enzymes, with a focus on region-specificity and diversity, are summarized and the
      production of mono-, di-, and tri-hydroxy fatty acids is introduced. Finally, the
      production methods of regio-specific and diverse hydroxy fatty acids, such as
      gene screening, protein engineering, metabolic engineering, and combinatory
      biosynthesis, are suggested. 

PMID- 23860414
TI  - Change in physical activity after a diabetes diagnosis: opportunity for
      intervention.
AB  - INTRODUCTION: Moderate-intensity physical activity is recommended for individuals
      with diabetes to control glucose and prevent diabetes-related complications. The
      extent to which a diabetes diagnosis motivates patients to increase physical
      activity is unclear. This study used data from the Women's Health Initiative
      Observational Study (baseline data collected from 1993 to 1998) to examine change
      in physical activity and sedentary behavior in women who reported a diabetes
      diagnosis compared with women who did not report diabetes during 7 yr of follow
      up (up to 2005). METHODS: Participants (n = 84,300) were postmenopausal women who
      did not report diabetes at baseline (mean +/- SD; age = 63.49 +/- 7.34 yr; body
      mass index = 26.98 +/- 5.67 kg.m). Linear mixed-model analyses were conducted
      adjusting for study year, age, race/ethnicity, body mass index, education, family
      history of diabetes, physical functioning, pain, energy/fatigue, social
      functioning, depression, number of chronic diseases, and vigorous exercise at age
      18 yr. Analyses were completed in August 2012. RESULTS: Participants who reported
      a diabetes diagnosis during follow-up were more likely to report increasing their
      total physical activity (P = 0.002), walking (P < 0.001), and number of physical
      activity episodes (P < 0.001) compared with participants who did not report a
      diabetes diagnosis. On average, participants reporting a diabetes diagnosis
      reported increasing their total physical activity by 0.49 MET.h.wk, their walking
      by 0.033 MET.h.wk, and their number of physical activity episodes by 0.19
      MET.h.wk. No differences in reported sedentary behavior change were observed (P =
      0.48). CONCLUSIONS: A diabetes diagnosis may prompt patients to increase physical
      activity. Healthcare professionals should consider how best to capitalize on this
      opportunity to encourage increased physical activity and maintenance.

PMID- 23860415
TI  - A method to estimate free-living active and sedentary behavior from an
      accelerometer.
AB  - INTRODUCTION: Methods to estimate physical activity (PA) and sedentary behavior
      (SB) from wearable monitors need to be validated in free-living settings.
      PURPOSE: The purpose of this study was to develop and validate two novel machine
      learning methods (Sojourn-1 Axis [soj-1x] and Sojourn-3 Axis [soj-3x]) in a free
      living setting. METHODS: Participants were directly observed in their natural
      environment for 10 consecutive hours on three separate occasions. Physical
      activity and SB estimated from soj-1x, soj-3x, and a neural network previously
      calibrated in the laboratory (lab-nnet) were compared with direct observation.
      RESULTS: Compared with lab-nnet, soj-1x and soj-3x improved estimates of MET
      hours (lab-nnet: % bias [95% confidence interval] = 33.1 [25.9 to 40.4], root
      mean-square error [RMSE] = 5.4 [4.6-6.2]; soj-1x: % bias = 1.9 [-2.0 to 5.9],
      RMSE = 1.0 [0.6 to 1.3]; soj-3x: % bias = 3.4 [0.0 to 6.7], RMSE = 1.0 [0.6 to
      1.5]) and minutes in different intensity categories {lab-nnet: % bias = -8.2
      (sedentary), -8.2 (light), and 72.8 (moderate-to-vigorous PA [MVPA]); soj-1x: %
      bias = 8.8 (sedentary), -18.5 (light), and -1.0 (MVPA); soj-3x: % bias = 0.5
      (sedentary), -0.8 (light), and -1.0 (MVPA)}. Soj-1x and soj-3x also produced
      accurate estimates of guideline minutes and breaks from sedentary time.
      CONCLUSIONS: Compared with the lab-nnet algorithm, soj-1x and soj-3x improved the
      accuracy and precision in estimating free-living MET-hours, sedentary time, and
      time spent in light-intensity activity and MVPA. In addition, soj-3x is superior
      to soj-1x in differentiating SB from light-intensity activity.

PMID- 23860416
TI  - Are there negative responders to exercise training among heart failure patients?
AB  - PURPOSE: Aerobic exercise training has been used in patients with stable heart
      failure (HF) to reduce the risk of clinical events. However, due to patient
      heterogeneity, some patients may experience a decrease in functional capacity due
      to such training. The purpose of this study was to estimate the proportion of HF
      patients participating in a training program who had negative responses to such
      therapy and to compare them with a concurrent control group. METHODS: Baseline
      and 3-month peak VO2 measurements were obtained on 1870 HF subjects who were
      randomized to receive either an exercise training program or a control program of
      usual care without exercise training. The exercise program consisted of
      supervised walking or stationary cycling 3 d.wk(-1) for 12 wk as well as a 2
      d.wk(-1) home exercise program after completing 18 supervised sessions. A
      negative response was defined as a baseline-to-3-month decrease in peak VO2 of at
      least 5 mL.kg(-1) min(-1), which was two times the SD of the control group's
      change in peak VO2. RESULTS: The mean +/- SD change in peak VO2 in the exercise
      group and control group was 0.8 +/- 2.5 mL.kg(-1)min(-1) and 0.2 +/- 2.5 mL.kg(
      1)min(-1), respectively (P < 0.001). The percentage of negative responders in the
      exercise and control groups was 0.9% and 2.3% (P = 0.02). CONCLUSIONS: The low
      negative response rate in the exercise group combined with the slightly higher
      rate in the control group and equal variability in the exercise and control
      groups suggests that few if any subjects had training-related negative peak VO2
      responses. These findings support current exercise recommendations for HF
      patients.

PMID- 23860417
TI  - Physical activity, sedentary behavior, and C-reactive protein in pregnancy.
AB  - INTRODUCTION: Elevated C-reactive protein (CRP) is associated with adverse
      pregnancy outcomes. In nonpregnant populations, physical activity has been
      inversely associated with CRP, but this association has not been evaluated during
      pregnancy. The purpose of this study was to evaluate the association between
      objectively measured physical activity, sedentary behavior, and CRP by pregnancy
      trimester. METHODS: We evaluated this association among 294 pregnant participants
      in the National Health and Nutrition Examination Survey (2003-2004 and 2005
      2006). Physical activity (min.d(-1)) was assessed via accelerometer using
      established cut points. CRP (mg.L(-1)) was measured using a high sensitivity
      assay. Multivariable linear regression was used to determine the relationship
      between physical activity, sedentary behavior, and CRP by trimester of pregnancy.
      RESULTS: Among women in the second trimester, after adjusting for age, body mass
      index, smoking status, and history of adverse pregnancy outcomes, light-intensity
      physical activity was associated with lower CRP (beta = -0.002, P = 0.05). In
      unadjusted models, sedentary time and proportion of wear time spent sedentary
      were positively associated with CRP (beta = 0.048, P = 0.02 and beta = 2.36, P =
      0.03, respectively); however, the relationship was no longer statistically
      significant in multivariable models (beta = 0.33, P = 0.2 and beta = 1.96, P =
      0.08, respectively). Neither physical activity nor sedentary behavior was
      associated with CRP among women in the first or third trimester. CONCLUSIONS:
      Objectively measured light-intensity physical activity had a protective effect on
      CRP among women in the second trimester of pregnancy. Findings highlight the need
      for longitudinal studies of pregnancy physical activity and CRP with careful
      control for clinical characteristics of the current pregnancy.

PMID- 23860418
TI  - Efficient fabrication of nanoporous si and Si/Ge enabled by a heat scavenger in
      magnesiothermic reactions.
AB  - Magnesiothermic reduction can directly convert SiO2 into Si nanostructures.
      Despite intense efforts, efficient fabrication of highly nanoporous silicon by Mg
      still remains a significant challenge due to the exothermic reaction nature. By
      employing table salt (NaCl) as a heat scavenger for the magnesiothermic
      reduction, we demonstrate an effective route to convert diatom (SiO2) and
      SiO2/GeO2 into nanoporous Si and Si/Ge composite, respectively. Fusion of NaCl
      during the reaction consumes a large amount of heat that otherwise collapses the
      nano-porosity of products and agglomerates silicon domains into large crystals.
      Our methodology is potentially competitive for a practical production of
      nanoporous Si-based materials. 

PMID- 23860419
TI  - Task- and age-dependent effects of visual stimulus properties on children's
      explicit numerosity judgments.
AB  - Researchers investigating numerosity processing manipulate the visual stimulus
      properties (e.g., surface). This is done to control for the confound between
      numerosity and its visual properties and should allow the examination of pure
      number processes. Nevertheless, several studies have shown that, despite
      different visual controls, visual cues remained to exert their influence on
      numerosity judgments. This study, therefore, investigated whether the impact of
      the visual stimulus manipulations on numerosity judgments is dependent on the
      task at hand (comparison task vs. same-different task) and whether this impact
      changes throughout development. In addition, we examined whether the influence of
      visual stimulus manipulations on numerosity judgments plays a role in the
      relation between performance on numerosity tasks and mathematics achievement. Our
      findings confirmed that the visual stimulus manipulations affect numerosity
      judgments; more important, we found that these influences changed with increasing
      age and differed between the comparison and the same-different tasks.
      Consequently, direct comparisons between numerosity studies using different tasks
      and age groups are difficult. No meaningful relationship between the performance
      on the comparison and same-different tasks and mathematics achievement was found
      in typically developing children, nor did we find consistent differences between
      children with and without mathematical learning disability (MLD). 

PMID- 23860420
TI  - Carbon materials as new nanovehicles in hot-melt drug deposition.
AB  - The application of commercially available carbon materials (nanotubes and porous
      carbons) for the preparation of drug delivery systems is studied. We used two
      types of carbon nanotubes (CNT) and two activated carbons as potential materials
      in so-called hot-melt drug deposition (HMDD). The materials were first studied
      using Raman spectroscopy. Paracetamol was chosen as a model drug. The performed
      thermal analysis, kinetics, and adsorption-desorption studies revealed that
      nanoaggregates are formed between carbon nanotubes. In contrast, in pores of
      activated carbon we do not observe this process and the drug adsorption
      phenomenon mechanism is simply the filling of small pores. The formation of
      nanoaggregates was confirmed by the results of GCMC (grand canonical Monte Carlo)
      simulations and the study of the surface area on nitrogen adsorption-desorption
      isotherms. The application of carbon nanotubes in HMDD offers the possibility of
      controlling the rate of drug delivery. Performed MTT tests of nanotubes and drug
      loaded nanotubes show that the observed decrease in cell viability number is
      caused by the influence of the cytostatic properties of nanotubes-they inhibit
      the proliferation of cells. The carbon nanotubes studied in this paper are
      essentially nontoxic. 

PMID- 23860421
TI  - The effect of a flexible pylon system on functional mobility of transtibial
      amputees. A prospective randomized study.
AB  - BACKGROUND: Prosthetic component selection strongly influences the functional
      mobility of transtibial amputees. Until now, little attention has been paid to
      the connection between the prosthetic socket and the foot component. AIM AND
      DESIGN: Aim of this study was to compare a novel flexible with a conventional
      rigid pylon system in a prospective randomized trial in transtibial amputees to
      determine effects on gait and mobility. SETTING: The study was performed in a
      rehabilitation centre for geriatric amputees. POPULATION: Twenty-eight geriatric
      unilateral transtibial amputees (8 female, 20 male) with low degree of mobility
      were included. METHODS: At admission to the rehabilitation centre objective and
      subjective parameters were assessed including demographic data and levels of
      daily activity using standardized questionnaires. Three months after prosthetic
      fitting a follow-up was performed and additional parameters such as walking
      speed, step length and vertical ground reaction forces were examined using a
      dynamic gait analysis. RESULTS: The study revealed a significant improvement in
      step length (P=0.03), in using mobility aids (P=0.04) and benefits concerning the
      self-selected gait speed, the mobility and gait disorders using the flexible
      device. CONCLUSION: The results demonstrate advantages for the flexible system,
      resulting in a positive effect on the patient's gait accomplishments in a
      geriatric population. CLINICAL REHABILITATION IMPACT: The advantages of the
      dynamic pylon may improve clinical rehabilitation, especially for geriatric
      patients with vascular disorders, as it provides comfort and better prosthetic
      performance during gait as a short-term benefit and thus gives a better quality
      of life in the long-term.

PMID- 23860423
TI  - Characteristics of flexed knee gait and functional outcome of a patient who
      underwent knee reconstruction with a hingeless prosthesis for bone tumor
      resection: a case report with gait analysis and comparison with healthy subjects.
AB  - We report on a patient after knee reconstruction for osteosarcoma in the distal
      femur using a hingeless prosthesis K-MAX KNEE system K-5 who walked without
      ipsilateral knee extension in the latter half of the stance phase (flexed knee
      gait). We evaluated the patient using three-dimensional gait analysis and
      isokinetic knee strength measurement, and compared the patient with five healthy
      subjects. The Musculoskeletal Tumor Society (MSTS) score was also used for
      evaluation. The patient kept his operated knee flexed during mid stance. The
      maximal ankle plantarflexion internal moment was lower on the ipsilateral side
      than on the contralateral side, and lower than in the healthy subjects. The
      negative ankle power during the stance phase was generally stronger on the
      ipsilateral side than on the contralateral side, and also in the healthy
      subjects. Unusual contralateral hip flexion occurred after the initial contact,
      indicating increased joint load on the ipsilateral ankle and the contralateral
      hip. The ratios of the peak knee extension/flexion torque were 0.7 on the
      ipsilateral side, 1.9 on the contralateral side, and 1.7 in the healthy subjects.
      The MSTS score of the patient was 23/30 (76.6%). Flexed knee gait might account
      for the reduction of ipsilateral hip flexion and ankle plantarflexion moment
      during the late stance phase. These results suggest the importance of focusing
      more on the ipsilateral ankle joint and the contralateral hip joint to maintain
      the function of the entire limb joints of the patients with flexed knee gait.

PMID- 23860422
TI  - Alpha lipoic acid and superoxide dismutase in the treatment of chronic low back
      pain.
AB  - BACKGROUND: Neuropathic mechanisms largely contribute to low back pain (LBP) and
      oxidative stress is acknowledged as one of the causes of nerve damage typical of
      neuropathic pain: antioxidant agents may be a useful choice in the multimodal
      treatment strategy for chronic LBP patients. AIM: The aim of this study was to
      detect changes in perceived pain, functional activity and in the assumption of
      analgesics in patients with chronic LBP treated with a combination of alpha
      lipoic acid (ALA) and superoxide dismutase (SOD). DESIGN: Prospective non
      randomized open-label study. SETTING: Outpatient at TAMMEF (Therapeutic
      Application of Musically Modulated Electromagnetic Fields) Centre of the
      University of Siena. POPULATION: The study enrolled 98 adult patients with
      chronic (>=12 weeks) LBP with or without radiculopathy and without neoplastic or
      inflammatory pathologies. METHODS: Patients were treated for 60 days with 600 mg
      ALA and 140 UI SOD/die. The Roland Morris Disability Questionnaire and Pain
      Rating Scale were used and concomitant use of medications (with particular
      attention to analgesics) and adverse events (toxicity) were recorded during
      treatment. Differences between all the study time points were calculated for the
      scores of the two tools and for the need of concomitant treatment with
      analgesics. RESULTS: At the end of the study only 8% of patients still used
      analgesics versus 73.5% registered at baseline (P<0.01). Regarding self-reported
      tools, a statistically significant improvement both for perceived pain and
      functional disabilities occurred: pain ameliorated after 40 days of therapy and
      the improvement was significant both statistically (P<0.05) and clinically. Only
      4 patients stopped the treatment due to unacceptable pain (not related to the
      treatment). CONCLUSION: Oral treatment with ALA and SOD improves functionality
      and reduces the use of analgesics in chronic LBP patients. CLINICAL
      REHABILITATION IMPACT: Oral combination of ALA and SOD may be a powerful adjuvant
      in multimodal therapy of chronic LBP patients.

PMID- 23860424
TI  - Graphene oxide: efficiency of reducing agents.
AB  - The efficiency of reducing agents for the reduction of graphene oxide (GO) could
      be probed by scanning Raman spectroscopy. A film of graphene flakes derived from
      GO was probed to be graphene like. We also focus on the surface quality of
      reduced GO (rGO). 

PMID- 23860425
TI  - Securing the anterior chamber in penetrating keratoplasty: an innovative surgical
      technique.
AB  - PURPOSE: Conventional penetrating keratoplasty (PK) is an open-sky procedure,
      carrying a worrisome risk of expulsive suprachoroidal hemorrhage and vitreous
      prolapse in high-risk cases. The authors propose an innovative surgical technique
      that secures the intraoperative anterior chamber and should reduce the risk of
      vitreous complications. METHODS: In the new stabilized procedure, a deep anterior
      corneal lamella is excised. A small puncture is made in each quadrant along the
      groove of the stromal bed, and the anterior chamber is maintained by viscoelastic
      injection. The viscoelastic-coated graft is sutured near the 4 puncture sites.
      After sequential cutting of the stromal bed and suturing of the graft, the
      residual stromal bed is excised and drawn out before the last suture is placed.
      Fifteen PK patients have undergone this procedure without complications. RESULTS:
      Satisfactory vision recovery was achieved in all 15 of the stabilized PK eyes,
      and the mean postoperative endothelial cell loss was comparable to studies
      performed for open PK. CONCLUSIONS: The authors believe that the reduced risks
      and limited endothelial cell loss verify the significance and practicability of
      the stabilized PK. This innovative new technique adds security for keratoplasty
      candidates who are at high risk for vitreous prolapse or suprachoroidal
      hemorrhage.

PMID- 23860426
TI  - Changes in corneal sensation, epithelial damage, and tear function after descemet
      stripping automated endothelial keratoplasty.
AB  - PURPOSE: To study the ocular surface changes in eyes after Descemet stripping
      automated endothelial keratoplasty (DSAEK) compared with those after penetrating
      keratoplasty (PKP). METHODS: This prospective study compared the changes in 31
      eyes of 28 patients who underwent DSAEK (DSAEK group) with those in 15 disease
      matched eyes of 15 patients who underwent PKP (PKP group). Corneal epithelial
      integrity was evaluated using a fluorescein staining score. Corneal sensation was
      measured with a Cochet-Bonnet esthesiometer. Tear function was evaluated using
      the Schirmer test, tear clearance test, tear function index, and tear break-up
      time. RESULTS: The postoperative fluorescein staining score was significantly
      higher in the PKP group than in the DSAEK group (P = 0.02). Postoperative corneal
      sensation was significantly better in the DSAEK group than in the PKP group (P <
      0.01). Corneal sensation after DSAEK was significantly better than the
      preoperative value (P = 0.02). There were no statistically significant changes in
      the Schirmer test, tear clearance test, tear function index, or break-up time
      before and after the surgery in both the DSAEK and PKP groups. No significant
      differences were observed between the DSAEK and PKP groups after the surgery.
      CONCLUSIONS: Corneal sensation was preserved, and epithelial damage was less
      severe after DSAEK compared with PKP. Preservation of corneal sensation may
      contribute to the early recovery of visual function and long-term maintenance of
      ocular surface health after DSAEK.

PMID- 23860427
TI  - Scanning electron microscopy applied to impression cytology for conjunctival
      damage from glaucoma therapy.
AB  - PURPOSE: To apply scanning electron microscopy to impression cytology (IC) to
      evaluate conjunctival damage in patients undergoing topical glaucoma therapy.
      METHODS: All patients undergoing glaucoma therapy and without ocular surface
      disorders between September 2012 and January 2013 were enrolled. An age- and
      gender-matched group without glaucoma served as the control group. Conjunctival
      epithelium was evaluated with the ferning test (FT), impression cytology with
      light optic microscopy (ICOM), and impression cytology with scanning electron
      microscopy (ICSEM). RESULTS: Twenty patients (40 eyes; 11 men and 9 women, mean
      age 59.9 +/- 11 years) constituted the treated group. The mean duration of
      glaucoma therapy was 25.5 +/- 13.8 months (range, 6-48 months). The mean FT,
      ICOM, and ICSEM grades were 2.52 +/- 0.5, 2.52 +/- 0.6, and 2.55 +/- 0.7,
      respectively. Treatment duration was not significantly correlated with FT/IC
      grade (P = 0.1), whereas it was significantly correlated with microvilli count at
      ICSEM (P = 0.01). The mean FT, ICOM, and ICSEM grades were significantly lower in
      the control group (40 eyes; 11 men and 9 women, mean age 61.1 +/- 7.12 years)
      than in the treated group (1.22 +/- 0.4, 1.25 +/- 0.4 and 1.15 +/- 0.3,
      respectively, P < 0.001). CONCLUSIONS: The FT, ICOM, and ICSEM grades were lower
      in eyes undergoing glaucoma therapy than in control eyes. Treatment duration was
      significantly associated with a reduced microvilli count at ICSEM, but not with
      FT or ICOM grades. Reduction of microvilli could be the first sign of cellular
      damage during chronic glaucoma therapy.

PMID- 23860428
TI  - Comparison of synthetic glues and 10-0 nylon in rabbit lamellar keratoplasty.
AB  - PURPOSES: To evaluate changes in mean keratometry and to compare wound repair
      with corneal lamellar grafts in rabbit eyes using human synthetic tissue
      adhesives and 10-0 nylon. METHODS: Corneal grafts were made using a 6.0-mm
      diameter trephine and blades in the eyes of 15 New Zealand white rabbits. Human
      fibrin tissue adhesive (Tisseel) was used in group 1, human fibrin tissue
      adhesive (Beriplast P) was used in group 2, polyethylene glycol adhesive (Coseal)
      was used in group 3, and 8 bite sutures with 10-0 nylon were used in group 4
      (control) for lamellar keratoplasty. Four bite sutures were made with 10-0 nylon
      in groups 1, 2, and 3. Slit-lamp microscopy and keratometry were performed at 3
      days and 1, 2, and 4 weeks after the surgery. Histopathologic and
      electromicroscopic examinations were performed 4 weeks after the surgery.
      RESULTS: No inflammation or corneal toxicity was seen in groups 1 and 2.
      Histologically, a few inflammatory cells were seen in groups 3 and 4. Groups 1,
      2, and 3 showed no statistically significant changes in mean keratometry at 4
      weeks postoperatively compared with preoperative mean keratometry (Wilcoxon
      signed-rank test, P = 0.178, 0.208, and 0.889, respectively). The control group
      showed significant changes in mean keratometry at 4 weeks postoperatively
      (Wilcoxon signed-rank test, P = 0.018). CONCLUSIONS: Human fibrin tissue
      adhesives were well tolerated in rabbit eyes, with no apparent corneal toxicity.
      Polyethylene glycol adhesive showed more inflammation and insufficient wound
      repair compared with human fibrin tissue adhesives. Therefore, human fibrin
      tissue adhesives can be used as an alternative to sutures in lamellar
      keratoplasty.

PMID- 23860429
TI  - Plug surface defects as a late complication of silicone punctal plugs.
AB  - PURPOSE: To report 3 cases of punctal plug surface defects as a cause of
      irritation complicating punctal plug therapy. METHODS: Interventional case series
      and scanning electron microscopy (SEM) of punctal plugs. RESULTS: Three patients
      were found to have punctal plug surface defects and local irritation of
      conjunctiva and inferonasal cornea 9, 40, and 69 months after placement of
      AquaFlo silicone punctal plugs for the treatment of dry eyes. SEM of the
      explanted plugs confirmed a defective collarette surface. In addition, unused
      AquaFlo plugs from different lots examined by SEM showed a rough irregular
      collarette surface that was not seen in unused plugs of Parasol silicone punctal
      plugs. DISCUSSION: AquaFlo punctal plugs inherently have surface irregularities
      when compared with similar plug brands, which we suggest may predispose to plug
      breakdown over time, leading to mechanical irritation of the adjacent conjunctiva
      and cornea. This report highlights the local complications by AquaFlo punctal
      plugs associated with plug surface defects as a complication of punctal plug
      therapy.

PMID- 23860430
TI  - Detection of herpes simplex virus type 1 in failed descemet stripping automated
      endothelial keratoplasty grafts.
AB  - PURPOSE: To determine the prevalence of herpes simplex virus type 1 (HSV-1) DNA
      in failed Descemet membrane stripping automated endothelial keratoplasty (DSAEK)
      grafts. METHODS: A retrospective interventional case series of patients with
      DSAEK graft failure treated at the New York Eye and Ear Infirmary between January
      2009 and July 2012 was performed. Repeat DSAEK, penetrating keratoplasty, or
      keratoprosthesis procedure was subsequently performed on eyes with failed grafts.
      All failed grafts were examined immunohistochemically and with qualitative real
      time polymerase chain reaction for HSV-1 DNA. In HSV-1-positive cases,
      corneoscleral donor rims from the original DSAEK procedures were also examined
      immunohistochemically and with polymerase chain reaction. RESULTS: Fifty-one
      failed DSAEK grafts from 50 eyes of 49 patients were identified. Indications for
      DSAEK were pseudophakic bullous keratopathy (28/51, 55%), Fuchs corneal
      endothelial dystrophy (12/51, 23%), failed penetrating keratoplasty (7/51, 14%),
      corneal decompensation from glaucoma (2/51, 4%), herpetic endotheliitis (1/51,
      2%), and failed DSAEK (1/51, 2%). Forty-three grafts (83%) were primary DSAEK
      graft failure. HSV-1 DNA was isolated from 2 of 51 failed DSAEK grafts (4.0%).
      The corresponding corneoscleral donor rims did not demonstrate the presence of
      HSV-1. CONCLUSIONS: Based on our results, HSV-1 infection plays a minor role in
      DSAEK graft failure. The data suggest that recipient reactivation, rather than
      donor transmission, plays a role in HSV infection.

PMID- 23860431
TI  - In vitro efficacy of ocular surface lubricants against dehydration.
AB  - PURPOSE: To compare 3 ocular lubricants containing sodium hyaluronate (SH),
      carboxymethylcellulose (CMC), and hydroxypropyl methylcellulose (HPMC) for their
      ability to enhance water retention and to protect human corneal epithelial cells
      (HCECs) from dehydration. METHODS: Experiments were performed using 0.1% and 0.3%
      solutions of the 3 lubricants diluted in Milli-Q water for the water retention
      assays and in DMEM/F12 culture medium for the cell viability assays. Five
      milliliters of each of the lubricants was dropped onto a filter paper, and the
      paper was kept in an open container at 25 degrees C and a humidity of 36% to 38%.
      The weight of the paper was measured hourly for 4 hours. In the second set of
      experiment, cultured HCECs were exposed to the test lubricants for 60 minutes,
      and the lubricants were removed. Cells were then exposed to room air for up to 60
      minutes. Cells were then incubated with a vital dye, and the absorption of the
      reduced form of the dye was measured. The cell survival rate was compared for the
      3 lubricants. RESULTS: Filter papers moistened with both 0.1% and 0.3% SH were
      significantly heavier than those moistened with CMC and HPMC at all time points.
      The survival rate of HCECs was significantly higher at most times with 0.1% and
      0.3% SH than with CMC and HPMC solutions. The effects of CMC were not
      significantly different from those of HPMC. CONCLUSIONS: These findings indicate
      that SH is significantly better for water retention and protection of HCECs from
      dehydration than HPMC and CMC.

PMID- 23860433
TI  - The sensitivity and specificity of subjective memory complaints and the
      subjective memory rating scale, deterioration cognitive observee, mini-mental
      state examination, six-item screener and clock drawing test in dementia
      screening.
AB  - BACKGROUND: The effectiveness of dementia screening depends on the availability
      of suitable screening tools with good sensitivity and specificity to confidently
      distinguish normal age-related cognitive decline from dementia. The aim of this
      study was to evaluate the discriminant validity of 7 screening measures for
      dementia. METHODS: A sample of 140 participants aged >=60 years living in a
      residential facility for the aged were assessed clinically and assigned caseness
      for dementia using the Diagnostic and Statistical Manual of Mental Disorders, 4th
      edition, text revised diagnostic criteria. Sensitivity and specificity of a
      selection of the following screening measures were tested using receiver
      operating characteristic (ROC) analysis for individual and combined tests: the
      Mini-Mental State Examination (MMSE), Six-Item Screener (SIS), Subjective Memory
      Complaint, Subjective Memory Complaint Clinical (SMCC), Subjective Memory Rating
      Scale (SMRS), Deterioration Cognitive Observee (DECO) and the Clock Drawing Test
      (CDT). RESULTS: Using ROC analyses, the SMCC, MMSE and CDT were found to be
      'moderately accurate' in screening for dementia with an area under the curve
      (AUC) >0.70. The AUCs for the SIS (0.526), SMRS (0.661) and DECO (0.687)
      classified these measures as being 'less accurate'. At recommended cutoff scores,
      the SMCC had a sensitivity of 90.9% and specificity of 45.7%; the MMSE had a
      sensitivity of 63.6% and a specificity of 76.0%, and the CDT had a sensitivity of
      44.4% and a specificity of 88.9%. Combining the SMCC and MMSE did not improve
      their predictive power except for a modest increase when using the sequential
      rule. CONCLUSION: The SMCC is composed of valid screening questions that have
      high sensitivity, are simple to administer and ideal for administration at the
      community or primary health care level as a first level of 'rule-out' screening.
      The MMSE can be included at a second stage of screening at the general hospital
      level and the CDT in specialist clinical settings. Sequential use of the SMCC and
      MMSE will improve the specificity of the former and the sensitivity of the
      latter.

PMID- 23860434
TI  - Farewell message.

PMID- 23860432
TI  - Adiponectin receptor 1 C-terminus interacts with PDZ-domain proteins such as
      syntrophins.
AB  - Adiponectin receptor 1 (AdipoR1) is one of the two signaling receptors of
      adiponectin with multiple beneficial effects in metabolic diseases. AdipoR1 C
      terminal peptide is concordant with the consensus sequence of class I PSD-95,
      disc large, ZO-1 (PDZ) proteins, and screening of a liver yeast two hybrid
      library identified binding to beta2-syntrophin (SNTB2). Hybridization of a PDZ
      domain array with AdipoR1 C-terminal peptide shows association with PDZ-domains
      of further proteins including beta1- and alpha-syntrophin (SNTA). Interaction of
      PDZ proteins and C-terminal peptides requires a free carboxy terminus next to the
      PDZ-binding region and is blocked by carboxy terminal added tags. N-terminal
      tagged AdipoR1 is more highly expressed than C-terminal tagged receptor
      suggesting that the free carboxy terminus may form a complex with PDZ proteins to
      regulate cellular AdipoR1 levels. The C- and N-terminal tagged AdipoR1 proteins
      are mainly localized in the cytoplasma. N-terminal but not C-terminal tagged
      AdipoR1 colocalizes with syntrophins in adiponectin incubated Huh7 cells.
      Adiponectin induced hepatic phosphorylation of AMPK and p38 MAPK which are
      targets of AdipoR1 is, however, not blocked in SNTA and SNTB2 deficient mice.
      Further, AdipoR1 protein is similarly abundant in the liver of knock-out and wild
      type mice when kept on a standard chow or a high fat diet. In summary these data
      suggest that AdipoR1 protein levels are regulated by so far uncharacterized class
      I PDZ proteins which are distinct from SNTA and SNTB2.

PMID- 23860435
TI  - Safe introduction of robot-assisted radical prostatectomy after a training
      program in a high-volume robotic centre.
AB  - INTRODUCTION: Localized prostate cancer is increasingly treated by robot-assisted
      radical prostatectomy (RARP). We evaluated the introduction of RARP following a
      training program at a high-volume robotic center. MATERIALS AND METHODS: Before
      starting RARP, a young urologist followed a 6-month training program. The outcome
      of his first 50 RARPs was compared with the last 50 open radical prostatectomies
      (ORPs) performed by an experienced urologist at the same institution. Tumor
      characteristics were similar in both groups. Median follow-up was 12 (RARP) and
      31 (ORP) months (p < 0.001). RESULTS: RARP was associated with more nerve sparing
      (82 vs. ORP 46%, p < 0.001), longer operation time [median 205 (range 120-310)
      vs. ORP 180 (85-280) min, p = 0.001], lower decline of postoperative hemoglobin
      [RARP -2.1 (0.1-4.5) vs. ORP -4.0 (1.0-7.0) g/dl, p < 0.001] and shorter catheter
      stay [6 (5-47) vs. ORP 14 (9-43) days, p < 0.001]. Complication rates were
      similar. Overall and pT2-positive surgical margin rate was 8 vs. 24% (p = 0.054)
      and 0 vs. 11.8% (p = 0.114) for RARP vs. ORP, respectively. One-year urinary
      continence rate was 76.7 (RARP) and 75.8% (ORP, p = 0.833). CONCLUSIONS: RARP was
      safely introduced after a training program in a high-volume robotic center, both
      surgically, oncologically and functionally.

PMID- 23860436
TI  - Orientation dependent thermal conductance in single-layer MoS2.
AB  - We investigate the thermal conductivity in the armchair and zigzag MoS2
      nanoribbons, by combining the non-equilibrium Green's function approach and the
      first-principles method. A strong orientation dependence is observed in the
      thermal conductivity. Particularly, the thermal conductivity for the armchair
      MoS2 nanoribbon is about 673.6 Wm(-1) K(-1) in the armchair nanoribbon, and 841.1
      Wm(-1) K(-1) in the zigzag nanoribbon at room temperature. By calculating the
      Caroli transmission, we disclose the underlying mechanism for this strong
      orientation dependence to be the fewer phonon transport channels in the armchair
      MoS2 nanoribbon in the frequency range of [150, 200] cm(-1). Through the scaling
      of the phonon dispersion, we further illustrate that the thermal conductivity
      calculated for the MoS2 nanoribbon is esentially in consistent with the superior
      thermal conductivity found for graphene. 

PMID- 23860437
TI  - Growth hormone treatment adherence in prepubertal and pubertal children with
      different growth disorders.
AB  - BACKGROUND/AIMS: Treatment of children with growth disorders with recombinant
      human growth hormone is necessary for improved outcomes, including final height.
      METHODS: Adherence data from the Observational Study Saizen(r)-online, recorded
      with the easypodTM device collected between October 2009 and May 2011, were
      analyzed in pediatric patients receiving recombinant human growth hormone
      treatment for a variety of growth disorders. RESULTS: Data from 75 children (46
      boys, 29 girls) with different growth disorders were analyzed over a period of
      343 +/- 201 (SD) days. Boys and girls showed similar mean +/- SD adherence rates
      of 90.5 +/- 3.1% and 92.2 +/- 10.7%, respectively. Pubertal children (n = 41) had
      a significantly lower adherence rate (89.1 +/- 13.7%) than prepubertal children
      (n = 29) (96.5 +/- 3.9%; p < 0.005). There were nonsignificant differences in
      adherence rates according to diagnosis: growth hormone deficiency (n = 48) 91.4
      +/- 11.0%, small for gestational age (n = 18) 91.1 +/- 15.3%, Turner syndrome (n
      = 6) 86.0 +/- 14.5%, and chronic renal failure (n = 3) 99.3 +/- 1.0%, although
      the latter two groups were small. CONCLUSION: Our data indicate that only a small
      number of pediatric patients using the easypod device had poor adherence to
      treatment. Further reliable adherence data are required to identify factors
      affecting long-term adherence in this population.

PMID- 23860438
TI  - Short repeats in the spa gene of Staphylococcus aureus are prone to nonsense
      mutations: stop codons can be found in strains isolated from patients with
      generalized infection.
AB  - Fifteen sequences with stop codons have been obtained in the course of standard
      methicillin-resistant Staphylococcus aureus (MRSA) spa typing. In nine of those
      sequences, stop codons occurred due to nonsense G-T and A-T transversions. G-T
      transversions would appear to be frequent in the spa gene, mostly due to
      symmetric mutational AT-pressure in the whole S. aureus genome and due to
      replication-associated mutational pressure characteristic of lagging strands of
      the "chromosome". A-T transversions would appear to be frequent in the spa gene
      mostly due to transcription-associated mutational pressure. Relative to other S.
      aureus genes, short repeats in spa are enriched by nonsense sites for G-T and A-T
      transversions; the probability of being nonsense for A-T transversion is high in
      that part of spa coding region. 13 out of 15 (87%) of the sequences with stop
      codons were obtained from strains isolated from patients with generalized S.
      aureus infection. Truncation of spa at its C-terminus is predicted to result in a
      protein that possesses functional IgG binding domains unable to be linked to the
      cell wall. This is discussed in light of the known fact that extracellular spa is
      a strong virulence factor involved in immune evasion. 

PMID- 23860439
TI  - Mechanical forces and feedbacks in cell motility.
AB  - Cell movement is driven by a self-organized assembly of numerous actin polymers
      and accessory proteins surrounded by a flexible membrane. While the identity of
      the molecular components involved is largely known, we are still far from
      understanding how this enormous ensemble of molecules self-organizes into a
      dynamic motile cell. A great deal of work in the field has focused on the role of
      biochemical signaling in establishing and maintaining cellular organization. More
      recently, mechanical forces and feedbacks have emerged as equally important
      contributors to the large-scale organization of motile cells. Here we review
      recent progress in the field, focusing on processes related to the actin
      cytoskeleton and its interplay with the cell membrane. 

PMID- 23860440
TI  - Inflammatory and immunological biomarkers are not related to survival in adults
      with Cystic Fibrosis.
AB  - BACKGROUND: Chronic Pseudomonas aeruginosa pulmonary infection is associated with
      a decline in lung function and reduced survival in people with Cystic Fibrosis
      (CF). Damaging inflammatory and immunological mediators released in the lungs can
      be used as markers of chronic infection, inflammation and lung tissue damage.
      METHODS: Clinical samples were collected from CF patients and healthy controls.
      Serum IgG and IgA anti-Pseudomonas antibodies, sputum IL-8 and TNFalpha, plasma
      IL-6 and urine TNFr1 were measured by ELISA. Sputum neutrophil elastase (NE),
      cathepsin S and cathepsin B were measured by spectrophotometric and fluorogenic
      assays. The relationship between IgG and IgA, inflammatory mediators and long
      term survival was determined. RESULTS: IgG and IL-6 positively correlated with
      mortality. However, multivariate analysis demonstrated that after adjusting for
      FEV(1), IgG was not independently related to mortality. A relationship was
      observed between IgG and IL-6, TNFalpha, TNFr1 and between IgA and IL8, cathepsin
      S and cathepsin B. CONCLUSIONS: These data indicate that biomarkers of
      inflammation are not independent predictors of survival in people with CF.

PMID- 23860442
TI  - Validation of visual analogue scale for anxiety (VAS-A) in preanesthesia
      evaluation.
AB  - BACKGROUND: Anxiety is a relevant but still underscored perioperative problem.
      The Visual Analogue Scale for Anxiety (VAS-A) seems to be effective, fast and
      manageable, but has not been fully validated yet. The aim of this study is to
      validate VAS-A comparing it to, Corah's Dental Anxiety Scale (CDAS) Spielberger's
      State Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI).
      METHODS: One hundred consecutive patients (38 males and 62 females, median age 49
      years) submitted to oral surgery filled out the VAS-A, CDAS, STAI forms Y1 and
      Y2, and BDI at preoperative examination; the order of administration of tests was
      randomized. RESULTS: VAS-A score was significantly correlated to CDAS (P<0.0001),
      STAI-Y1 (P<0.0001), STAI-Y2 (P<0.002) but not to BDI (P=0.18). ROC curve analysis
      suggested VAS-A equal to 46 mm as threshold for anxiety when using STAI Y1 equal
      to 40 as reference cutoff. CONCLUSION: Our study confirms that VAS-A is a
      reliable indicator of preoperative anxiety and may detect patients with
      depressive symptoms also. Values of VAS-A around 50 mm are a reliable threshold
      for a clinically meaningful level of preoperative anxiety.

PMID- 23860443
TI  - Indeterminate and erroneous fine-needle aspirates of breast with focus on the
      'true gray zone': a review.
AB  - OBJECTIVE: To review our experience and the literature on inconclusive/erroneous
      fine-needle aspirates (FNAs) of breast with the focus on the 'true gray zone'. To
      describe the cytology, differential diagnosis, pitfalls and limitations of common
      and rare lesions. STUDY DESIGN: We conducted a literature search focusing on
      breast FNAs with statistical data of C3 and C4 categories including false
      positive and false-negative cases. Similar data from 2003 to 2009 was obtained
      from our institution. RESULTS: C3 and C4 categories account for 3-17% of breast
      FNAs. Contributing factors are technical difficulties, inexperienced pathologists
      interpreting FNAs of breast and overlap of cytologic features of certain benign
      and malignant conditions; this last, 'true gray zone' accounts for 2% of cases.
      Fibroadenoma, proliferative breast lesions, gynecomastia, infiltrating and in
      situ low-grade adenocarcinomas and tubular, cribriform, lobular and mucinous
      carcinomas are the most common problematic lesions. Granular cell tumor,
      adenomyoepithelioma, pregnancy-related lesions, fat necrosis, inflammatory and
      radiation changes, adenoid cystic carcinoma, spindle-cell lesions and Phyllodes
      tumor are less common. CONCLUSION: Inconclusive/erroneous FNAs of breast due to
      the 'true gray zone' are rare. Most are due to the overlapping cytologic features
      of some benign and malignant conditions. Practical features that may help arrive
      at the correct diagnoses are elucidated.

PMID- 23860441
TI  - High population frequencies of APOL1 risk variants are associated with increased
      prevalence of non-diabetic chronic kidney disease in the Igbo people from south
      eastern Nigeria.
AB  - BACKGROUND: Continental Africa is facing an epidemic of chronic kidney disease
      (CKD). APOL1 risk variants have been shown to be strongly associated with an
      increased risk for non-diabetic kidney disease including HIV nephropathy, primary
      non-monogenic focal and segmental glomerulosclerosis, and hypertension-attributed
      nephropathy among African ancestry populations in the USA. The world's highest
      frequencies of APOL1 risk alleles have been reported in West African nations,
      overlapping regions with a high incidence of CKD and hypertension. One such
      region is south-eastern Nigeria, and therefore we sought to quantify the
      association of APOL1 risk alleles with CKD in this region. METHODS: APOL1 risk
      variants were genotyped in a case-control sample set consisting of non-diabetic,
      CKD patients (n = 44) and control individuals (n = 43) from Enugu and Abakaliki,
      Nigeria. RESULTS: We found a high frequency of two APOL1 risk alleles in the
      general population of Igbo people of south-eastern Nigeria (23.3%). The two APOL1
      risk allele frequency in the CKD patient group was 66%. Logistic regression
      analysis under a recessive inheritance model showed a strong and significant
      association of APOL1 two-risk alleles with CKD, yielding an odds ratio of 6.4
      (unadjusted p = 1.2E-4); following correction for age, gender, HIV and BMI, the
      odds ratio was 4.8 (adjusted p = 5.1E-03). CONCLUSION: APOL1 risk variants are
      common in the Igbo population of south-eastern Nigeria, and are also highly
      associated with non-diabetic CKD in this area. APOL1 may explain the increased
      prevalence of CKD in this region.

PMID- 23860444
TI  - Spontaneous hydromyelic cavity in two unrelated patients with late-onset pompe
      disease: is this a fortuitous association?

PMID- 23860445
TI  - DNA photoreacts by nucleobase ring cleavage to form labile isocyanates.
AB  - Differential infrared absorption spectroscopy was used to study the formation of
      isocyanates and further photo-products in the oligonucleotides dG10, dC10 and
      dT10 and in their mononucleosides by ultraviolet light at 266 nm. We find that
      alpha-cleavage takes place in oligonucleotides and mononucleosides both in films
      and in solution. The very intense and spectrally isolated isocyanate (N=C=O)
      asymmetric stretch vibration at 2277 cm(-1) is used as a spectroscopic marker for
      detection of the photo-product. The band disappears upon reaction with small
      amounts of water vapour as expected for isocyanates. Quantum yields for
      isocyanate formation by nucleobase ring cleavage in the alpha-position to the
      carbonyl group are ~5 * 10(-5) in the mononucleosides and up to 5 * 10(-4) in the
      oligonucleotides. In the mixed oligonucleotides dG10/dC10 and dA10/dT10 the
      quantum yield of alpha-cleavage drops by a factor of 10 compared to the single
      oligonucleotides. Implications for DNA repair and photo-induced DNA-protein cross
      linking via isocyanate reaction with NH2 groups of amino acids are discussed.

PMID- 23860446
TI  - Chromatin dynamics at the hTERT promoter during transcriptional activation and
      repression by c-Myc and Mnt in Xenopus leavis oocytes.
AB  - The transcription factors c-Myc and Mnt regulate gene expression through
      dimerization with Max and binding to E-boxes in target genes. While c-Myc
      activates gene expression via recruitment of histone modifying complexes, Mnt
      acts as a transcriptional repressor. Here, we used the Xenopus leavis oocyte
      system to address the effect of c-Myc and Mnt on transcription and chromatin
      remodeling over the E-box region in the human telomerase reverse transcriptase
      (hTERT) promoter. As expected we found elevated and decreased levels of hTERT
      transcription upon exogenously expressed c-Myc/Max and Mnt/Max, respectively. In
      addition, we confirmed binding of these heterodimers to both E-boxes already
      enriched with H3K9ac and H4K16ac. These chromatin marks were further enhanced
      upon c-Myc/Max binding followed by increased DNA accessibility in the E-box
      region. In contrast, Mnt/Max inhibited Myc-induced transcription and mediated
      repression through complete chromatin condensation and deacetylation of H3K9 and
      H4K16 across the E-box region. Importantly, Mnt was able to counteract c-Myc
      mediated activation even when expressed at low levels, suggesting Mnt to act as a
      strong repressor by closing the chromatin structure. Collectively our data
      demonstrate that the balance between c-Myc and Mnt activity determines the
      transcriptional outcome of the hTERT promoter by modulation of the chromatin
      architecture. 

PMID- 23860447
TI  - Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic
      leukemia (CLL): a study on 852 patients.

PMID- 23860448
TI  - Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in
      multiple myeloma. A comparative analysis with flow cytometry.
AB  - We have analyzed the applicability, sensitivity and prognostic value of allele
      specific oligonucleotide real-time quantitative PCR (ASO RQ-PCR) as a method for
      minimal residual disease (MRD) assessment in patients with multiple myeloma (MM),
      comparing the results with those of multiparameter flow cytometry (MFC). A total
      of 170 patients enrolled in three consecutive Spanish trials achieving at least
      partial response after treatment were included. Lack of clonality detection
      (n=31), unsuccessful sequencing (n=17) and suboptimal ASO performance (n=51)
      limited the applicability of PCR to 42% of cases. MRD was finally investigated in
      103 patients (including 32 previously studied) with persistent disease identified
      by PCR and MFC in 54% and 46% of cases, respectively. A significant correlation
      in MRD quantitation by both the techniques was noted (r=0.881, P<0.001), being
      reflective of treatment intensity. Patients with <10(-4) residual tumor cells
      showed longer progression-free survival (PFS) compared with the rest (not reached
      (NR) vs 31 months, P=0.002), with similar results observed with MFC. Among
      complete responders (n=62), PCR discriminated two risk groups with different PFS
      (49 vs 26 months, P=0.001) and overall survival (NR vs 60 months, P=0.008). Thus,
      although less applicable than MFC, ASO RQ-PCR is a powerful technique to assess
      treatment efficacy and risk stratification in MM. 

PMID- 23860449
TI  - The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14)
      multiple myeloma.

PMID- 23860451
TI  - Prescribing controlled substances.

PMID- 23860452
TI  - Herpes zoster in older adults.

PMID- 23860453
TI  - Radiation, contrast media, and the pregnant patient.

PMID- 23860450
TI  - Establishing optimal quantitative-polymerase chain reaction assays for routine
      diagnosis and tracking of minimal residual disease in JAK2-V617F-associated
      myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST
      action BM0902) study.
AB  - Reliable detection of JAK2-V617F is critical for accurate diagnosis of
      myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific
      assays can be applied to monitor disease response. However, there has been no
      consistent approach to JAK2-V617F detection, with assays varying markedly in
      performance, affecting clinical utility. Therefore, we established a network of
      12 laboratories from seven countries to systematically evaluate nine different
      DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical
      use. Seven quality control rounds involving over 21,500 qPCR reactions were
      undertaken using centrally distributed cell line dilutions and plasmid controls.
      The two best-performing assays were tested on normal blood samples (n=100) to
      evaluate assay specificity, followed by analysis of serial samples from 28
      patients transplanted for JAK2-V617F-positive disease. The most sensitive assay,
      which performed consistently across a range of qPCR platforms, predicted outcome
      following transplant, with the mutant allele detected a median of 22 weeks (range
      6-85 weeks) before relapse. Four of seven patients achieved molecular remission
      following donor lymphocyte infusion, indicative of a graft vs MPN effect. This
      study has established a robust, reliable assay for sensitive JAK2-V617F
      detection, suitable for assessing response in clinical trials, predicting outcome
      and guiding management of patients undergoing allogeneic transplant.

PMID- 23860454
TI  - Minimizing legal risks when prescribing.

PMID- 23860455
TI  - Constipation in older adults.
AB  - Constipation is a common complaint in the general population, particularly among
      older adults. Patients present with infrequent bowel movements or difficulty
      passing stools. Management of this uncomfortable condition involves diet, fluid
      intake, and medications. 

PMID- 23860458
TI  - 2013 National Conference for Nurse Practitioners.

PMID- 23860459
TI  - Talking about CAMs for menopause.
AB  - This article discusses the integration of complementary and alternative medicine
      therapies as part of the healthcare decision-making dialogue between nurse
      practitioners and patients seeking relief of menopause-related symptoms. 

PMID- 23860461
TI  - Desymmetrization of 4,6-diprotected myo-inositol.
AB  - The asymmetric desymmetrization of 4,6-diprotected myo-inositol derivatives was
      achieved by using a bifunctional, readily available nucleophilic catalyst. The
      orthogonally protected products were obtained in 80-99% yield with 90-99% ee.
      Such structures serve as potential enantiopure building blocks for the synthesis
      of myo-inositol phosphates. 

PMID- 23860462
TI  - Activation of eosinophils is more closely linked with interleukin-5 and nitric
      oxide production than tumor necrosis factor-alpha and immunoglobulin E levels.

PMID- 23860463
TI  - Discovery of a kernel for controlling biomolecular regulatory networks.
AB  - Cellular behavior is determined not by a single molecule but by many molecules
      that interact strongly with one another and form a complex network. It is unclear
      whether cellular behavior can be controlled by regulating certain molecular
      components in the network. By analyzing a variety of biomolecular regulatory
      networks, we discovered that only a small fraction of the network components need
      to be regulated to govern the network dynamics and control cellular behavior. We
      defined a minimal set of network components that must be regulated to make the
      cell reach a desired stable state as the control kernel and developed a general
      algorithm for identifying it. We found that the size of the control kernel was
      related to both the topological and logical characteristics of a network.
      Intriguingly, the control kernel of the human signaling network included many
      drug targets and chemical-binding interactions, suggesting therapeutic
      application of the control kernel. 

PMID- 23860465
TI  - Evaluation of a novel endobronchial ultrasound-guided lymph node forceps in
      enlarged mediastinal lymph nodes.
AB  - BACKGROUND: Endobronchial ultrasound-transbronchial nee dle aspiration (EBUS
      TBNA) is a useful technique for cytological assessment of enlarged mediastinal
      lymph nodes with a high diagnostic yield for lung cancer. However, the small
      sample volume can be problematic in diagnosing benign diseases and for molecular
      analysis of malignant tumours. OBJECTIVES: The aim of the study was to evaluate a
      novel lymph node forceps for EBUS-guided lymph node biopsy (EBUS-transbronchial
      forceps biopsy; EBUS-TBFB) in malignant and benign conditions concerning safety,
      feasibility, and diagnostic yield. METHODS: Patients with enlarged mediastinal or
      hilar lymph nodes were included. EBUS-TBNA was performed followed by EBUS-guided
      TBFB with the lymph node forceps. Three biopsy specimens were obtained. The
      diagnostic yields of EBUS-TBFB, EBUS-TBNA, and the combination of both sampling
      techniques were compared. Complications were systematically recorded. RESULTS:
      Fifty-five patients with enlarged mediastinal nodes were enrolled into this
      study. Specimens adequate for histological analysis were obtained in all but one
      case using EBUS-TBFB. EBUS-TBFB increased the diagnostic yield of EBUS-TBNA from
      64 to 93% in benign conditions. The overall diagnostic yield was higher compared
      to EBUS-TBNA alone. EGFR mutation analysis could be achieved in the forceps
      biopsy samples as needed. No complications were observed. CONCLUSIONS: EBUS-TBFB
      with a novel lymph node forceps is safe and provides adequate histological
      specimens of enlarged mediastinal lymph nodes. EBUS-TBFB increases the diagnostic
      yield in benign conditions and may add value in molecular analysis of non-small
      cell lung cancer.

PMID- 23860466
TI  - Local dynamics in decision making: The evolution of preference within and across
      decisions.
AB  - Within decisions, perceived alternatives compete until one is preferred. Across
      decisions, the playing field on which these alternatives compete evolves to favor
      certain alternatives. Mouse cursor trajectories provide rich continuous
      information related to such cognitive processes during decision making. In three
      experiments, participants learned to choose symbols to earn points in a
      discrimination learning paradigm and the cursor trajectories of their responses
      were recorded. Decisions between two choices that earned equally high-point
      rewards exhibited far less competition than decisions between choices that earned
      equally low-point rewards. Using positional coordinates in the trajectories, it
      was possible to infer a potential field in which the choice locations occupied
      areas of minimal potential. These decision spaces evolved through the
      experiments, as participants learned which options to choose. This visualisation
      approach provides a potential framework for the analysis of local dynamics in
      decision-making that could help mitigate both theoretical disputes and disparate
      empirical results. 

PMID- 23860467
TI  - Anti-aquaporin-4 antibody positivity in neuromyelitis optica is associated with
      lesion activity.
AB  - AIMS: To assess the demographic, clinical and spinal cord MRI characteristics of
      clinically definite neuromyelitis optica (NMO) patients for association with anti
      aquaporin-4 (AQP4) antibody positivity in Chinese patients. METHODS: We recruited
      72 consecutive patients with NMO. The clinical assessments, sera and spinal MRI
      scans were obtained within 1 week after the onset of symptoms of acute myelitis.
      The statistical significance of potential differences in demographic, clinical
      and spinal MRI lesion characteristics between the two groups (anti-AQP4 antibody
      positive vs. negative) was determined using the two-sample t test or Fisher's
      exact test. RESULTS: Forty-nine patients (49/72, 68.1%) were anti-AQP4 antibody
      positive and 23 patients (23/72, 31.9%) were anti-AQP4 antibody negative. The
      only characteristic that was significantly different between the groups was the
      presence of an enhancing spinal cord lesion (p < 0.001). CONCLUSION: We found a
      strong association between serum anti-AQP4 antibody positivity and lesional
      gadolinium enhancement in patients with clinically definite NMO. These findings
      support prior evidence that anti-AQP4 antibody could be pathogenic in NMO lesion
      development.

PMID- 23860468
TI  - Subjectivity and schizophrenia: another look at incomprehensibility and treatment
      nonadherence.
AB  - Psychiatry is in a time of crisis. The absence of significant breakthroughs to
      actionable etiological knowledge has left the discipline in a state of
      uncertainty and worries are being voiced about its status and future. In our
      view, the stagnation can be, at least in part, ascribed to an excessive,
      behaviorist-oriented, epistemological, and ontological simplification of
      psychopathology. The aim of this phenomenological study is to articulate the
      notion of the 'disordered self' in schizophrenia, a notion that we believe
      constitutes an important step forward in grasping its essential pathogenetic
      structures. Through the framework of self-disorders, we analyze two domains of
      the psychopathology of schizophrenia, seeking to recast their puzzling nature
      into more useful clinical and scientific terms. First, we examine the so-called
      schizophrenic incomprehensibility (bizarre gestalt, bizarre delusions, and 'crazy
      actions') and argue that grasping the altered framework for experiencing,
      associated with the disordered self, makes these phenomena appear comprehensible
      to a considerable extent. Second, we explore the issue of treatment noncompliance
      and provide a novel account of 'poor insight' into illness. We propose that poor
      insight into schizophrenia is not simply a problem of insufficient self-
      reflection due to psychological defenses or impaired metacognition, but rather
      that it is intrinsically expressive of the severity and nature of self-disorders.
      The instabilities of the first-person perspective throw the patient into a
      different, often quasisolipsistic, ontological-existential framework. We argue
      that interventions seeking to optimize the patients' compliance might prove more
      efficient if they take the alterations of the patients' ontological-existential
      framework into account.

PMID- 23860470
TI  - The impact of compulsory drug detention exposure on the avoidance of healthcare
      among injection drug users in Thailand.
AB  - BACKGROUND: Although Thailand has relied on the use of compulsory drug detention
      centres as a strategy to try to address problematic drug use, little is known
      about the effects of exposure to these centres on people who inject drugs (IDU).
      Therefore, we undertook this study to explore whether exposure to compulsory drug
      detention was associated with avoiding healthcare among Thai IDU. METHODS: Using
      Poisson regression analyses, we examined the relationship between compulsory drug
      detention exposure and avoiding healthcare among participants in the Mitsampan
      Community Research Project based in Bangkok. RESULTS: 435 IDU participated in
      this study, including 111 (25.5%) participants who reported avoiding healthcare.
      In multivariate analyses, avoiding healthcare was positively associated with
      exposure to compulsory drug detention (adjusted prevalence ratio [APR]=1.60; 95%
      confidence interval [CI]: 1.16-2.21), having been refused healthcare (APR=3.46;
      95% CI: 2.61-4.60), and experiencing shame associated with one's drug use
      (APR=1.93; 95% CI: 1.21-3.09). CONCLUSION: Exposure to compulsory drug detention
      was associated with avoiding healthcare among Thai IDU, suggesting that this
      system of detention may be contributing to the burden of preventable morbidity
      among IDU in this setting. Although further research is needed to confirm these
      findings, the results of this study reinforce previous calls to replace the
      system of compulsory drug detention with evidence-based public health
      interventions for IDU.

PMID- 23860471
TI  - "It gives me a sense of belonging": providing integrated health care and
      treatment to people with HCV engaged in a psycho-educational support group.
AB  - BACKGROUND: Injection drug use (IDU) increases the risk of contracting hepatitis
      C virus (HCV) yet very few people living with HCV access effective, and
      potentially curative, treatments. The East Toronto Hepatitis C Program (ETHCP)
      was developed in 2006 and provides health care, treatment and support to people
      living with HCV who have complex mental health, physical health and psychosocial
      needs. The program is anchored in a 16-18 week psychosocial support group located
      within one of the 3 participating community-based health clinics. The objective
      of this study was to explore the experiences of individuals engaged in the ETHCP
      psycho-educational group. METHODS: This phenomenological qualitative study
      consisted of semi-structured in-depth interviews with twenty randomly selected
      program participants. RESULTS: The three dominant themes that emerged from the
      analysis were program structure, group cohesion and group as agent for change.
      The ETHCP "one-stop shopping" model provided a stable foundation allowing for the
      development of group cohesion. Group cohesion was marked by the formation of
      intense relationships creating a safe and non-judgmental environment where
      participants could self-reflect, make social connections and feel cared for and
      accepted. Three types of relationships characterized group cohesion: relationship
      to self, relationships with individual group members and relationship to group as
      a whole. Within the nurturing group environment, participants could challenge
      themselves and others, ultimately enabling change. CONCLUSION: The results of our
      qualitative study suggest that it is the formation of strong group cohesion that
      facilitated participants' behavioural change, regardless of their level of
      substance use. The structure of the group provided stability and was
      characterized by consistent weekly meetings, knowledge exchange and the provision
      of multiple services in one location. The support from peers and staff allowed
      participants to develop personal goals. Participants began to see themselves in a
      new and changed way; expressing this change in a variety of positive behaviours.

PMID- 23860472
TI  - Spiritual/religious coping in patients with epilepsy: relationship with
      sociodemographic and clinical aspects and quality of life.
AB  - One hundred and ten patients with epilepsy with a mean age of 45.9 were assessed
      by a clinical-neurological evaluation, Quality of Life in Epilepsy Inventory-31
      (QOLIE-31), and the Spiritual/Religious Coping (SRCOPE) Scale. The objective of
      this study was to evaluate if patients with epilepsy used positive and/or
      negative spiritual/religious coping and the relationships between this type of
      coping and the sociodemographic and clinical aspects of epilepsy and the QOLIE
      31. A greater use of positive coping (3.0+/-0.7) than negative coping (2.3+/-0.7)
      was found. The use of the positive factor was greater in mesial temporal lobe
      epilepsy (MTLE) than in other types of epilepsy. The ratio of negative/positive
      coping was associated with lower scores in the QOLIE-31 (-0.222; p=0.036).
      Patients with epilepsy appear to use spiritual/religious coping, especially those
      with MTLE, and a predominance of negative coping was associated with a reduced
      quality of life. Future studies should evaluate interventions considering the
      knowledge of spiritual/religious strategies by the patients. 

PMID- 23860473
TI  - Obesity in adults with epilepsy.
AB  - Sixty-eight percent of the US adult population is overweight, and 35% is obese.
      The rate of obesity in patients with epilepsy is unknown. Its determination was
      the goal of the present study. Weight and height were measured, and body mass
      index (BMI) was calculated in all newly evaluated patients with epilepsy at a
      single epilepsy center between 2003 and 2009. Five hundred fifty-four patients
      aged >=16-87years were included (62.7% were women, 12.6% with primary generalized
      epilepsy, and 86.4% with localization-related epilepsy). Three hundred six
      (55.2%) patients were overweight or obese (BMI>25kg/m(2)) (95% confidence
      interval [CI]: 51.1%-59.3%), 173 (31.2%) were obese (BMI>30kg/m(2)) (95% CI:
      27.5%-35.2%), and 24 (4.3%) were morbidly obese (BMI>40kg/m(2)).
      Overweight/obesity combined was more common in men (65.4% [95% CI: 58.8%-71.5%])
      than in women (49% women [95% CI: 43.3%-54.3%]) (p<=0.001). The rate of
      overweight/obesity combined trended to be greater in blacks (67.9%) than in
      whites (51.9%). Obesity alone was more common in blacks (46.4%) than in whites
      (29.4%), with too few Hispanics and Asians to allow a comparison.
      Overweight/obesity and obesity rates were higher in patients with refractory than
      nonrefractory epilepsy (60.4% vs. 49.2% overweight, 36.9% vs.24.6% obesity).
      Obesity was more common in patients treated with polytherapy than those treated
      with monotherapy (37.7% vs. 25%). There were no associations between obesity and
      other disease characteristics such as epilepsy type, duration, or etiology.
      Obesity is common in patients with epilepsy, similar to the general population. 

PMID- 23860474
TI  - Fine needle aspiration cytopathology of liver masses: 101 cases with cyto
      /histopathological analysis.
AB  - OBJECTIVE: Appropriate clinical management of a hepatic mass depends on its
      accurate diagnosis. We aimed to evaluate sensitivity, specificity and accuracy of
      percutaneous fine needle aspiration cytopathology (FNAC) in the diagnosis of
      suspicious liver masses in our center. STUDY DESIGN: Cytopathology and
      histopathology databases were searched for patients undergoing combined, image
      guided percutaneous FNAC and biopsy sampling of liver mass lesions in 2006-2011.
      All patients had one or more radiologically detected lesion and clinical
      suspicion of neoplastic disease. Sensitivity, specificity and accuracy of FNAC in
      the diagnosis of liver lesions were determined using histopathological diagnoses
      on liver biopsy as a gold standard. RESULTS: Of 101 patients, cytopathological
      diagnoses were nonneoplastic in 10 cases while 10 cases were suspicious for
      neoplasms and 71 were malignant. In 10 patients (9.9%), FNA samples were
      inadequate for assessment. Final histopathological diagnoses were nonneoplastic
      in 7 cases, benign tumoral in 5 and malignant in 89 cases (88.1%). Of the
      malignancies, 22 (24.7%) were hepatocellular carcinomas (HCC) and 60 (67.4%) were
      metastatic tumors on final clinicohistopathological analysis. The remaining 7
      (7.8%) patients had other primary hepatic malignancies. Fifteen of the 22 (68.2%)
      HCC cases were specifically diagnosed by FNAC. In 28 of the metastatic tumors,
      the primary organ site was unknown, followed by gastrointestinal malignancies in
      17 cases. Overall, sensitivity, specificity, accuracy, and positive and negative
      predictive values of FNAC in the diagnosis of neoplastic lesions were 96.3, 90.0,
      95.6, 98.7 and 75.0%, respectively. Discrepancy in cyto-/histopathological data
      was mainly seen in nonrepresentative FNAC cases. CONCLUSION: FNAC of liver masses
      is a highly accurate technique that can be used to identify the majority of
      primary/metastatic hepatic neoplasias with high specificity. A combined cyto
      /histopathological approach provides higher accuracy in the diagnosis and typing
      of hepatic tumors, which may affect therapeutic decisions. Correlation of
      cytopathology with clinicoradiological findings is helpful to increase overall
      accuracy of the procedure.

PMID- 23860475
TI  - Multifunctional biohybrid hydrogels for cell culture and controlled drug release.
AB  - Here we reported a novel biohybrid hydrogel system with the potential for cell
      culture and controlled drug release. 

PMID- 23860476
TI  - Ovarian steroid hormones: effects on immune responses and Chlamydia trachomatis
      infections of the female genital tract.
AB  - Female sex hormones are known to regulate the adaptive and innate immune
      functions of the female reproductive tract. This review aims to update our
      current knowledge of the effects of the sex hormones estradiol and progesterone
      in the female reproductive tract on innate immunity, antigen presentation,
      specific immune responses, antibody secretion, genital tract infections caused by
      Chlamydia trachomatis, and vaccine-induced immunity. 

PMID- 23860477
TI  - What do parents have to do with my cognitive reserve? Life course perspectives on
      twelve-year cognitive decline.
AB  - BACKGROUND/AIMS: To examine the cognitive reserve hypothesis by comparing the
      contribution of early childhood and life course factors related to cognitive
      functioning in a nationally representative sample of older Americans. METHODS: We
      examined a prospective, national probability cohort study (Health and Retirement
      Study; 1998-2010) of older adults (n=8,833) in the contiguous 48 United States.
      The main cognitive functioning outcome was a 35-point composite of memory
      (recall), mental status, and working memory tests. The main predictors were
      childhood socioeconomic position (SEP) and health, and individual-level adult
      achievement and health. RESULTS: Individual-level achievement indicators (i.e.,
      education, income, and wealth) were positively and significantly associated with
      baseline cognitive function, while adult health was negatively associated with
      cognitive function. Controlling for individual-level adult achievement and other
      model covariates, childhood health presented a relatively small negative, but
      statistically significant association with initial cognitive function. Neither
      individual achievement nor childhood SEP was statistically linked to decline over
      time. CONCLUSIONS: Cognitive reserve purportedly acquired through learning and
      mental stimulation across the life course was associated with higher initial
      global cognitive functioning over the 12-year period in this nationally
      representative study of older Americans. We found little supporting evidence that
      childhood economic conditions were negatively associated with cognitive function
      and change, particularly when individual-level achievement is considered.

PMID- 23860478
TI  - The prognostic impact of absolute lymphocyte and monocyte counts at diagnosis of
      diffuse large B-cell lymphoma in the rituximab era.
AB  - BACKGROUND: A recent report showed that the combination of the absolute
      lymphocyte count (ALC) and the absolute monocyte count (AMC) at diagnosis gave a
      prognostic score in diffuse large B-cell lymphoma (DLBCL). However, this model
      requires validation in other patient cohorts. METHODS: We retrospectively
      evaluated the prognostic impact of the combination of the ALC and the AMC at
      diagnosis in a cohort of 299 DLBCL patients who were treated in the rituximab era
      at a single institution. RESULTS: In univariate analyses, an ALC <=1.0 * 10(9)/l
      [4-year overall survival (OS) rate 47.0 vs. 79.4%; p < 0.001] and an AMC >=0.63 *
      10(9)/l (4-year OS rate 52.4 vs. 75.6%; p < 0.001) were associated with inferior
      OS, respectively. In multivariate analyses, an ALC <=1.0 * 10(9)/l and an AMC
      >=0.63 * 10(9)/l were significantly associated with inferior OS independently of
      the International Prognostic Index. Furthermore, the combination of ALC and AMC
      could identify patients with the dismal prognosis; the 4-year OS rates for
      patients with ALC <=1.0 * 10(9)/l and AMC >=0.63 * 10(9)/l were 18.8%.
      CONCLUSIONS: The combination of ALC and AMC at diagnosis may be useful for the
      prognostic stratification of patients with DLBCL.

PMID- 23860479
TI  - Acute otitis media otopathogens during 2008 to 2010 in Rochester, New York.
AB  - BACKGROUND: The otopathogen distribution colonizing the nasopharynx (NP) and
      causing acute otitis media (AOM) is in flux following the introduction of
      pneumococcal conjugate vaccine 7 (PCV7) and will continue to change. METHODS: Two
      hundred seventy-seven children were followed prospectively; tympanocentesis was
      performed during AOM and 208 NP samples were collected to compare with middle ear
      fluid (MEF) isolates. Eight hundred sixty-three NP samples were collected at 7
      healthy visits between 6 and 30 months of age. All children received PCV7 until
      April 2010 when it was substituted by PCV13. Multilocus sequence typing was used
      to speciate Streptococcus pneumoniae. RESULTS: The distribution of otopathogens
      in the MEF during the study time frame was stable. PCV7 serotypes of pneumococci
      were virtually absent. The frequency of isolation of S. pneumoniae was 26-36%
      compared with 28-34% for nontypeable Haemophilus influenzae. Moraxella
      catarrhalis isolation was less common, 7-18%. The proportion of S. pneumoniae
      that were penicillin nonsusceptible was stable during the 3 years, 40-52%. All M.
      catarrhalis and 34% of nontypeable H. influenzae were beta-lactamase producing.
      NP isolates of otopathogens at onset of AOM included the isolate from the MEF and
      was dissimilar from the distribution at times of health. Sequence types 320 and
      199 of S. pneumoniae expressing serotypes 19A and 15 most often caused AOM.
      CONCLUSIONS: The otopathogen distribution, antibiotic susceptibility and the
      diversity of strains within the S. pneumoniae species during 2008 through late
      2010 were stable. NP isolation of otopathogens at onset of AOM better reflected,
      albeit incompletely, likely MEF isolates compared with NP isolates at times of
      health.

PMID- 23860481
TI  - Poor early virologic performance and durability of abacavir-based first-line
      regimens for HIV-infected children.
AB  - BACKGROUND: Concerns about stavudine (d4T) toxicity have led to increased use of
      abacavir (ABC) in first-line pediatric antiretroviral treatment (ART) regimens.
      Field experience with ABC in ART-naive children is limited. METHODS: Deidentified
      demographic, clinical and laboratory data on HIV-infected children initiating ART
      between 2004 and 2011 in a large pediatric HIV treatment program in Johannesburg,
      South Africa, were used to compare viral suppression at 6 and 12 months by
      initial treatment regimen, time to suppression (<400 copies/mL) and rebound
      (>1000 copies/mL after initial suppression). Adjusted logistic regression was
      used to investigate confounders and calendar effects. RESULTS: Two thousand
      thirty-six children initiated either d4T/3TC- or ABC/3TC-based first-line
      regimens in combination with either boosted lopinavir (LPV/r) or efavirenz (EFV).
      1634 received d4T regimens (LPV/r n = 672; EFV n = 962) and 402 ABC regimens
      (LPV/r n = 192; EFV n = 210). At 6 and 12 months on ART, viral suppression rate
      was poorer in ABC versus d4T groups within both the LPV/r and EFV groups (P <
      0.0001 for all points). In ABC groups, time to suppression was significantly
      slower (log-rank P < 0.0001 and P = 0.0092 for LPV/r- and EFV-based,
      respectively) and time to rebound after suppression significantly faster (log
      rank P = 0.014 and P = 0.0001 for LPV/r- and EFV-based, respectively). Logistic
      regression confirmed the worse outcomes in the ABC groups even after adjustment
      for confounders. CONCLUSION: Data from this urban pediatric ART service program
      show significantly poorer virological performance of ABC compared with d4T-based
      regimens, a signal that urgently warrants further investigation.

PMID- 23860480
TI  - Undervaccination of perinatally HIV-infected and HIV-exposed uninfected children
      in Latin America and the Caribbean.
AB  - BACKGROUND: Perinatally HIV-infected (PHIV) children may be at risk of
      undervaccination. Vaccination coverage rates among PHIV and HIV-exposed
      uninfected (HEU) children in Latin America and the Caribbean were compared.
      METHODS: All PHIV and HEU children born from 2002 to 2007 who were enrolled in a
      multisite observational study conducted in Latin America and the Caribbean were
      included in this analysis. Children were classified as up to date if they had
      received the recommended number of doses of each vaccine at the appropriate
      intervals by 12 and 24 months of age. Fisher's exact test was used to analyze the
      data. Covariates potentially associated with a child's HIV status were considered
      in multivariable logistic regression modeling. RESULTS: Of 1156 eligible
      children, 768 (66.4%) were HEU and 388 (33.6%) were PHIV. HEU children were
      significantly (P < 0.01) more likely to be up to date by 12 and 24 months of age
      for all vaccines examined. Statistically significant differences persisted when
      the analyses were limited to children enrolled before 12 months of age.
      Controlling for birth weight, sex, primary caregiver education and any use of
      tobacco, alcohol or illegal drugs during pregnancy did not contribute
      significantly to the logistic regression models. CONCLUSIONS: PHIV children were
      significantly less likely than HEU children to be up to date for their childhood
      vaccinations at 12 and 24 months of age, even when limited to children enrolled
      before 12 months of age. Strategies to increase vaccination rates in PHIV are
      needed.

PMID- 23860482
TI  - Cerebrospinal Abeta11-x and 17-x levels as indicators of mild cognitive
      impairment and patients' stratification in Alzheimer's disease.
AB  - In the present work, the concentrations of Abeta11-x and Abeta17-x peptides (x=40
      or 42), which result from the combined cleavages of beta-amyloid precursor
      protein (AbetaPP) by beta'/alpha or alpha/gamma-secretases, respectively, were
      assessed in cerebrospinal fluid (CSF) samples from patients with Alzheimer's
      disease (AD) or mild cognitive impairment (MCI). Specific multiplexed assays were
      set up using new anti-40 and anti-42 monoclonal antibodies (mAbs) for the capture
      of these N-truncated Abeta peptides and anti-11 or anti-17 mAbs for their
      detection. The specificity, sensitivity and reproducibility of such assays were
      assessed using synthetic peptides and human cell models. Abeta11-x and Abeta17-x
      were then measured in CSF samples from patients with AD (n=23), MCI (n=23) and
      controls with normal cognition (n=21). Abeta11-x levels were significantly lower
      in patients with MCI than in controls. Compared with the combined quantification
      of Abeta1-42, total Tau (T-Tau) and phosphorylated Tau (P-Tau; AlzBio3,
      Innogenetics), the association of Abeta11-40, Abeta17-40 and T-Tau improved the
      discrimination between MCI and controls. Furthermore, when patients with MCI were
      classified into two subgroups (MCI <=1.5 or >=2 based on their CDR-SB (Cognitive
      Dementia Rating-Sum of Boxes) score), the CSF Abeta17-40/Abeta11-40 ratio was
      significantly higher in patients with CDR-SB <=1.5 than in controls, whereas
      neither Abeta1-42, T-Tau nor P-Tau allowed the detection of this subpopulation.
      These results need to be confirmed in a larger clinical prospective cohort.

PMID- 23860485
TI  - A rare case of congenital distal renal tubular acidosis combined with medullary
      sponge kidney.
AB  - Distal renal tubular acidosis combined with medullary sponge kidney (MSK) is not
      uncommon in adults, but is rare in infants. We report a 13-month-old boy with MSK
      who had features of distal renal tubular acidosis (nephrocalcinosis,
      hypercalciuria, hypocitraturia) and failed to thrive. Renal ultrasound revealed
      bilateral increased medullary echogenicity and nephrocalcinosis. Bilateral
      medullary nephrocalcinosis in the ultrasound was the first sign that alerted our
      pediatrician to the presence of MSK in infants. Earlier treatment may increase
      efficacy.

PMID- 23860484
TI  - Human amygdala volume is predicted by common DNA variation in the stathmin and
      serotonin transporter genes.
AB  - Despite the relevance of changes in amygdala volume to psychiatric illnesses and
      its heritability in both health and disease, the influence of common genetic
      variation on amygdala morphology remains largely unexplored. In the present
      study, we investigated the influence of a number of novel genetic variants on
      amygdala volume in 139 neurologically healthy individuals of European descent.
      Amygdala volume was significantly associated with allelic variation in the
      stathmin (STMN1) and serotonin transporter (SLC6A4) genes, which have been linked
      to healthy and disordered affective processing. These results were replicated
      across both manual and automated methods of amygdala parcellation, although
      manual tracing showed stronger effects, providing a cautionary note to studies
      relying on automated parcellation methods. Future studies will need to determine
      whether amygdala volume mediates the impact of stathmin and serotonin transporter
      gene variants on normal and dysfunctional emotion processing.

PMID- 23860483
TI  - Use of functional imaging across clinical phases in CNS drug development.
AB  - The use of novel brain biomarkers using nuclear magnetic resonance imaging holds
      potential of making central nervous system (CNS) drug development more efficient.
      By evaluating changes in brain function in the disease state or drug effects on
      brain function, the technology opens up the possibility of obtaining objective
      data on drug effects in the living awake brain. By providing objective data,
      imaging may improve the probability of success of identifying useful drugs to
      treat CNS diseases across all clinical phases (I-IV) of drug development. The
      evolution of functional imaging and the promise it holds to contribute to drug
      development will require the development of standards (including good imaging
      practice), but, if well integrated into drug development, functional imaging can
      define markers of CNS penetration, drug dosing and target engagement (even for
      drugs that are not amenable to positron emission tomography imaging) in phase I;
      differentiate objective measures of efficacy and side effects and responders vs
      non-responders in phase II, evaluate differences between placebo and drug in
      phase III trials and provide insights into disease modification in phase IV
      trials. 

PMID- 23860486
TI  - The crystal structure of an isopenicillin N synthase complex with an ethereal
      substrate analogue reveals water in the oxygen binding site.
AB  - Isopenicillin N synthase (IPNS) is a non-heme iron oxidase central to the
      biosynthesis of beta-lactam antibiotics. IPNS converts the tripeptide delta-(L
      alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N while reducing
      molecular oxygen to water. The substrate analogue delta-(L-alpha-aminoadipoyl)-L
      cysteinyl-O-methyl-D-threonine (ACmT) is not turned over by IPNS. Epimeric delta
      (L-alpha-aminoadipoyl)-L-cysteinyl-O-methyl-D-allo-threonine (ACmaT) is converted
      to a bioactive penam product. ACmT and ACmaT differ from each other only in the
      stereochemistry at the beta-carbon atom of their third residue. These substrates
      both contain a methyl ether in place of the isopropyl group of ACV. We report an
      X-ray crystal structure for the anaerobic IPNS:Fe(II):ACmT complex. This
      structure reveals an additional water molecule bound to the active site metal,
      held by hydrogen-bonding to the ether oxygen atom of the substrate analogue.

PMID- 23860487
TI  - Existential vulnerability: toward a psychopathology of limit situations.
AB  - Jaspers' concept of limit situations seems particularly appropriate not only to
      elucidate outstanding existential situations in general, but also basic
      preconditions for the occurrence of mental disorders. For this purpose, the
      concept is first explained in Jaspers' sense and then related to an 'existential
      vulnerability' of mentally ill persons that makes them experience even
      inconspicuous events as distressing limit situations. In such situations, an
      otherwise hidden fundamental condition of existence becomes manifest for them,
      e.g. the fragility of one's own body, the inevitability of freedom, or the
      finiteness of life. This fundamental condition is found unbearable and, as a
      reaction, gives rise to mental illness. This concept of existential vulnerability
      is illustrated by some psychopathological examples.

PMID- 23860488
TI  - Quantum internet using code division multiple access.
AB  - A crucial open problem inS large-scale quantum networks is how to efficiently
      transmit quantum data among many pairs of users via a common data-transmission
      medium. We propose a solution by developing a quantum code division multiple
      access (q-CDMA) approach in which quantum information is chaotically encoded to
      spread its spectral content, and then decoded via chaos synchronization to
      separate different sender-receiver pairs. In comparison to other existing
      approaches, such as frequency division multiple access (FDMA), the proposed q
      CDMA can greatly increase the information rates per channel used, especially for
      very noisy quantum channels. 

PMID- 23860489
TI  - Recovery of African horse sickness virus from synthetic RNA.
AB  - African horse sickness virus (AHSV) is an insect-vectored emerging pathogen of
      equine species. AHSV (nine serotypes) is a member of the genus Orbivirus, with a
      morphology and coding strategy similar to that of the type member, bluetongue
      virus. However, these viruses are distinct at the genetic level, in the proteins
      they encode and in their pathobiology. AHSV infection of horses is highly
      virulent with a mortality rate of up to 90 %. AHSV is transmitted by Culicoides,
      a common European insect, and has the potential to emerge in Europe from endemic
      countries of Africa. As a result, a safe and effective vaccine is sought
      urgently. As part of a programme to generate a designed highly attenuated
      vaccine, we report here the recovery of AHSV from a complete set of RNA
      transcripts synthesized in vitro from cDNA clones. We have demonstrated the
      generation of mutant and reassortant AHSV genomes, their recovery, stable
      passage, and characterization. Our findings provide a new approach to investigate
      AHSV replication, to design AHSV vaccines and to aid diagnosis. 

PMID- 23860492
TI  - Effect of water and ammonia on surface species formed during NO(x) storage
      reduction cycles over Pt-K/Al2O3 and Pt-Ba/Al2O3 catalysts.
AB  - The effect of water, in the temperature range 25-350  degrees C, and ammonia at
      RT on two different surface species formed on Pt-K/Al2O3 and Pt-Ba/Al2O3 NSR
      catalysts during NO(x) storage-reduction cycles was investigated. The surface
      species involved are nitrates, formed during the NO(x) storage step, and
      isocyanates, which are found to be intermediates in N2 production during
      reduction by CO. FT-IR experiments demonstrate that the dissociative
      chemisorption of water and ammonia causes the transformation of the bidentate
      nitrates and linearly bonded NCO(-) species into more symmetric species that we
      call ionic species. In the case of water, the effect on nitrates is observable at
      all the temperatures studied; however, the extent of the transformation decreases
      upon increasing temperature, consistent with the decreased extent of
      dissociatively adsorbed water. It was possible to hypothesize that the
      dissociative chemisorption of water and ammonia takes place in a competitive way
      on surface sites able to give bidentate nitrates and linearly bonded NCO(-) that
      are dislocated, remaining on the surface as ionic species.

PMID- 23860490
TI  - Phylogenetic and histological variation in avipoxviruses isolated in South
      Africa.
AB  - Thirteen novel avipoxviruses were isolated from birds from different regions of
      South Africa. These viruses could be divided into six groups, according to gross
      pathology and pock appearance on chick chorioallantoic membranes (CAMs).
      Histopathology revealed distinct differences in epidermal and mesodermal cell
      proliferation, as well as immune cell infiltration, caused by the different
      avipoxviruses, even within groups of viruses causing similar CAM gross pathology.
      In order to determine the genetic relationships among the viruses, several
      conserved poxvirus genetic regions, corresponding to vaccinia virus (VACV) A3L
      (fpv167 locus, VACV P4b), G8R (fpv126 locus, VLTF-1), H3L (fpv140 locus, VACV
      H3L) and A11R-A12L (fpv175-176 locus) were analysed phylogenetically. The South
      African avipoxvirus isolates in this study all grouped in clade A, in either
      subclade A2 or A3 of the genus Avipoxvirus and differ from the commercial fowlpox
      vaccines (subclade A1) in use in the South African poultry industry. Analysis of
      different loci resulted in different branching patterns. There was no correlation
      between gross morphology, histopathology, pock morphology and phylogenetic
      grouping. There was also no correlation between geographical distribution and
      virus phenotype or genotype. 

PMID- 23860493
TI  - Central adiposity and mortality after first-ever acute ischemic stroke.
AB  - BACKGROUND: The waist-to-height ratio (WHtR) may be a better adiposity measure
      than the body mass index (BMI). We evaluated the prognostic performance of WHtR
      in patients with acute ischemic stroke (AIS). METHODS: First, we compared WHtR
      and BMI as adiposity measures in 712 healthy adults by tetrapolar bioimpedance
      analysis. Thereafter, baseline WHtR was analyzed as predictor of 12-month all
      cause mortality in 821 Mexican mestizo adults with first-ever AIS by a Cox
      proportional hazards model adjusted for baseline predictors. RESULTS: In healthy
      individuals, WHtR correlated higher than BMI with total fat mass and showed a
      higher accuracy in identifying a high percentage of body fat (p < 0.01). In AIS
      patients a U-shaped relationship was observed between baseline WHtR and mortality
      (fatality rate 29.1%). On multivariate analysis, baseline WHtR <= 0.300 or >0.800
      independently predicted 12-month all-cause mortality (hazard ratio 1.91, 95%
      confidence interval 1.04-3.51). BMI was not associated with mortality, tested
      either as continuous, binomial or stratified variable. CONCLUSION: WHtR is a
      modifiable risk factor that accurately demonstrates body fat excess. Extreme WHtR
      values were associated with increased 12-month all-cause mortality in Mexican
      mestizo patients with AIS. No survival advantage was found with high WHtR as the
      pragmatic indicator of obesity in this population.

PMID- 23860494
TI  - BRAF test and cytological diagnosis with a single fine needle cytology sample.
AB  - OBJECTIVE: Recently, fine needle cytology (FNC) of the thyroid has been combined
      with biomolecular analysis. In particular, there has been detailed study of the
      V600E-BRAF mutation. The aim of our study is to demonstrate that with a single
      thyroid sample it is possible to obtain enough cellular material for both
      cytological diagnosis and a V600E-BRAF molecular test. STUDY DESIGN: FNC was
      carried out under ultrasound guidance aided by an echographist and
      cytopathologist. We acquired one biopsy for each nodule with a 23-gauge needle
      without suction. The preparations were smeared by the pathologist onto one glass
      slide, air dried and stained with Diff-Quick. Cell adequacy was evaluated for
      each patient. The needle was washed by aspirating 2 ml of physiologic solution
      which was collected into a tube. The material was collected for molecular
      testing. RESULTS: The following cytological diagnoses were made: not neoplastic,
      Tir2 (n = 227); indeterminate, Tir3 (n = 15); suspicious, Tir4 (n = 4), and
      malignancy, Tir5 (n = 12). The V600E-BRAF mutation was found in 0 of 227 Tir2
      specimens, 2 of 15 (13.3%) Tir3 specimens, 2 of 4 (50%) Tir4 specimens and 9 of
      12 (75%) Tir5 specimens. CONCLUSIONS: Our data showed that, in a routine clinical
      setting, FNC specimens can be handled properly to provide both morphological and
      molecular information. In fact, our tests show that with a single specimen it is
      possible to set up a slide for the cytological diagnosis and to obtain enough
      residual cellular material for DNA extraction (>70 ng) and for the identification
      of the V600E-BRAF mutation.

PMID- 23860495
TI  - A red fluorescent turn-on probe for hydrogen sulfide and its application in
      living cells.
AB  - A novel selective fluorescent chemosensor has been synthesized with a
      phenanthrene-fused dipyrromethene structure. Selective binding of Cu(2+) by
      results in a complex that displays high selectivity and sensitivity for H2S. The
      signal transduction occurs via reversible formation-separation of the complex and
      CuS. Its potential utility for biological applications was confirmed by
      fluorescence imaging of H2S in live cells. 

PMID- 23860496
TI  - Medium to long term results following single stage Snodgrass hypospadias repair.
AB  - INTRODUCTION: The Snodgrass technique for primary hypospadias repair was
      described in 1994 and involves dorsal incision and tubularisation of the urethral
      plate distal to the meatus. While the advantages of good short-term outcome and
      good cosmesis have been reported, there is little data on long-term results in
      patients who have undergone a Snodgrass repair as a primary procedure for
      hypospadias. Our aim is to retrospectively review our medium to long-term results
      of primary tubularised incised-plate urethroplasty for hypospadias repair over a
      two-year period with up to eight-year follow-up. PATIENTS AND METHODS: We
      conducted a case note review of 74 patients who had undergone single-stage
      Snodgrass hypospadias repair, performed by a single surgeon (AB), from April 2000
      to January 2003. RESULTS: The mean documented follow up was 56 months (3-103
      months). The mean age of patients at time of surgery was three and a half years.
      95% (70) of patients had a distal (glanular, coronal, sub-coronal, distal shaft)
      meatus and 5% (4) had a proximal (mid-shaft) meatus. The overall complication
      rate was 7% (5). Two patients developed fistulae, which was noted and repaired at
      six months post-op with no further surgical intervention required. One patient
      underwent an EUA and meatal advancement glansplasty at 6 months for mild glanular
      dehiscence. Two further patients required EUA and dilatation procedures at two
      and three years respectively, both for mild meatal stenosis. Again, no further
      intervention was required. From a cosmetic perspective, two patients were noted
      to have some residual bulkiness of the skin around the corona and a further two
      patients were noted to have a small meatus, but with no functional symptoms.
      CONCLUSION: Our study has shown a low long-term complication rate in patients
      undergoing Snodgrass repair as a primary procedure for distal and midshaft
      hypospadias repair. This supports the results of earlier studies that have shown
      good functional and cosmetic outcome in the short-term for this procedure which
      persists into the medium/long term.

PMID- 23860497
TI  - Effect of composting on the Cd, Zn and Mn content and fractionation in feedstock
      mixtures with wood chips from a short-rotation coppice and bark.
AB  - Micronutrient content and availability in composts may be affected by the
      addition of wood chips or tree bark as a bulking agent in the compost feedstock.
      In the first part of this study, micronutrient levels were assessed in bark and
      wood of poplar and willow clones in a short-rotation coppice. Large differences
      between species were observed in bark concentrations for Cd, Zn and Mn. In the
      second part of the study, we aimed to determine the effect of feedstock
      composition and composting on Cd, Zn and Mn concentrations and availability. By
      means of three composting experiments we examined the effect of (a) bark of
      different tree species, (b) the amount of bark, and (c) the use of bark versus
      wood chips. In general, compost characteristics such as pH, organic matter and
      nutrient content varied due to differences in feedstock mixture and composting
      process. During the composting process, the availability of Cd, Zn and Mn
      decreased, although the use of willow and poplar bark or wood chips resulted in
      elevated total Cd, Zn or Mn concentrations in the compost. Cd concentrations in
      some composts even exceeded legal criteria. Cd and Zn were mainly bound in the
      reducible fraction extracted with 0.5M NH2OH?HCl. A higher acid-extractable
      fraction for Mn than for Cd and Zn was found. Higher Cd concentrations in the
      compost due to the use of bark or wood chips did not result in higher risk of Cd
      leaching. The results of the pH-stat experiment with gradual acidification of
      composts illustrated that only a strong pH decline in the compost results in
      higher availability of Cd, Zn and Mn. 

PMID- 23860498
TI  - Targeted proteomics reveals strain-specific changes in the mouse insulin and
      central metabolic pathways after a sustained high-fat diet.
AB  - The metabolic syndrome is a collection of risk factors including obesity, insulin
      resistance and hepatic steatosis, which occur together and increase the risk of
      diseases such as diabetes, cardiovascular disease and cancer. In spite of intense
      research, the complex etiology of insulin resistance and its association with the
      accumulation of triacylglycerides in the liver and with hepatic steatosis remains
      not completely understood. Here, we performed quantitative measurements of 144
      proteins involved in the insulin-signaling pathway and central metabolism in
      liver homogenates of two genetically well-defined mouse strains C57BL/6J and
      129Sv that were subjected to a sustained high-fat diet. We used targeted mass
      spectrometry by selected reaction monitoring (SRM) to generate accurate and
      reproducible quantitation of the targeted proteins across 36 different samples
      (12 conditions and 3 biological replicates), generating one of the largest
      quantitative targeted proteomics data sets in mammalian tissues. Our results
      revealed rapid response to high-fat diet that diverged early in the feeding
      regimen, and evidenced a response to high-fat diet dominated by the activation of
      peroxisomal beta-oxidation in C57BL/6J and by lipogenesis in 129Sv mice. 

PMID- 23860499
TI  - Central nervous system lymphoma newly developed 12 years after remission of an
      ocular adnexal lymphoma.
AB  - Recurrence of non-Hodgkin's lymphoma more than 5 years after the initial
      diagnosis is rare. When late relapse occurs, it is difficult to determine whether
      it is a true recurrence or a new lesion. We experienced a case of an 81-year-old
      woman who developed central nervous system (CNS) lymphoma 12 years after
      remission of ocular adnexal lymphoma. Both showed the histology of diffuse large
      B-cell lymphoma. To elucidate whether the CNS lymphoma was clonally related to
      the first lymphoma, rearrangement of the immunoglobulin heavy chain genes of each
      lymphoma was studied using a polymerase chain reaction-based method. The results
      revealed that the sizes of the amplified products of the rearranged regions from
      the two lymphomas were different. This suggested different clonal origins of the
      lymphomas. It is clinically important to determine the origin of a second
      neoplasm because patients with a clonally related second lymphoma are usually
      treated with more intensive regimens, while those with a clonally unrelated
      lymphoma receive standard first-line therapy. The present case shows that, in the
      case of recurrent non-Hodgkin's lymphoma, not only histological confirmation but
      also genetic assessment is important to clarify the origin of the second
      lymphoma. 

PMID- 23860500
TI  - Endothelial PAS domain protein 1 activates the inflammatory response in the
      intestinal epithelium to promote colitis in mice.
AB  - BACKGROUND & AIMS: Hypoxic inflammation (decreased oxygen tension at sites of
      inflammation) is a feature of inflammatory bowel disease (IBD). The hypoxia
      response is mediated by the transcription factors hypoxia-inducible factor (HIF)
      1alpha and endothelial PAS domain protein 1 (EPAS1 or HIF2alpha), which are
      induced in intestinal tissues of patients with IBD. HIF1alpha limits intestinal
      barrier dysfunction, but the role of EPAS1 has not been assessed under conditions
      of hypoxic inflammation or in models of IBD. METHODS: Acute colitis was induced
      by administration of Citrobacter rodentium or dextran sulfate sodium (DSS) to
      transgenic hypoxia reporter mice (oxygen-dependent degradation-luciferase), mice
      with conditional overexpression of Epas1 (Epas1(LSL/LSL)), mice with intestinal
      epithelium-specific deletion of Epas1 (Epas1(DeltaIE) ), or wild-type littermates
      (controls). Colon tissues from these mice and from patients with ulcerative
      colitis or Crohn's disease were assessed by histologic and immunoblot analyses,
      immunohistochemistry, and quantitative polymerase chain reaction. RESULTS: Levels
      of hypoxia and EPAS1 were increased in colon tissues of mice after induction of
      colitis and patients with ulcerative colitis or Crohn's disease compared with
      controls. Epas1(DeltaIE) mice had attenuated colonic inflammation and were
      protected from DSS-induced colitis. Intestine-specific overexpression of EPAS1,
      but not HIF-1alpha, led to spontaneous colitis, increased susceptibility to
      induction of colitis by C rodentium or DSS, and reduced survival times compared
      with controls. Disruption of intestinal epithelial EPAS1 attenuated the
      inflammatory response after administration of DSS or C rodentium, and intestine
      specific overexpression of EPAS1 increased this response. We found EPAS1 to be a
      positive regulator of tumor necrosis factor-alpha production by the intestinal
      epithelium. Blocking tumor necrosis factor-alpha completely reduced hypoxia
      induced intestinal inflammation. CONCLUSIONS: EPAS1 is a transcription factor
      that activates mediators of inflammation, such as tumor necrosis factor-alpha, in
      the intestinal epithelium and promotes development of colitis in mice.

PMID- 23860501
TI  - Dual oxidases control release of hydrogen peroxide by the gastric epithelium to
      prevent Helicobacter felis infection and inflammation in mice.
AB  - BACKGROUND & AIMS: Dual oxidases (DUOX) are conserved reduced nicotinamide
      adenine dinucleotide phosphate oxidases that produce H2O2 at the epithelial cell
      surface. The DUOX enzyme comprises the DUOX and DUOX maturation factor (DUOXA)
      subunits. Mammalian genomes encode 2 DUOX isoenzymes (DUOX1/DUOXA1 and
      DUOX2/DUOXA2). Expression of these genes is up-regulated during bacterial
      infections and chronic inflammatory diseases of the luminal gastrointestinal
      tract. The roles of DUOX in cellular interactions with microbes have not been
      determined in higher vertebrates. METHODS: Mice with disruptions of Duoxa1 and
      Duoxa2 genes (Duoxa(-/-) mice) and control mice were infected with Helicobacter
      felis to create a model of Helicobacter pylori infection--the most common human
      chronic infection. RESULTS: Infection with H. felis induced expression of Duox2
      and Duoxa2 in the stomachs of wild-type mice, and DUOX protein specifically
      localized to the apical surface of epithelial cells. H. felis colonized the mucus
      layer in the stomachs of Duoxa(-/-) mice to a greater extent than in control
      mice. The increased colonization persisted into the chronic phase of infection
      and correlated with an increased, yet ineffective, inflammatory response. H.
      felis colonization also was increased in Duoxa(+/-) mice, compared with controls.
      We observed reduced expression of the H2O2-inducible katA gene in H. felis that
      colonized Duoxa(-/-) mice, compared with that found in controls (P = .0002),
      indicating that Duox causes oxidative stress in these bacteria. In vitro,
      induction of oxidative defense by H. felis failed to prevent a direct
      bacteriostatic effect at sustained levels of H2O2 as low as 30 MUmol/L.
      CONCLUSIONS: Based on studies of Duoxa(-/-) mice, the DUOX enzyme complex
      prevents gastric colonization by H. felis and the inflammatory response. These
      findings indicate the nonredundant function of epithelial production of H2O2 in
      restricting microbial colonization.

PMID- 23860502
TI  - Simple noninvasive systems predict long-term outcomes of patients with
      nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Some patients with nonalcoholic fatty liver disease (NAFLD)
      develop liver-related complications and have higher mortality than other patients
      with NAFLD. We determined the accuracy of simple, noninvasive scoring systems in
      identification of patients at increased risk for liver-related complications or
      death. METHODS: We performed a retrospective, international, multicenter cohort
      study of 320 patients diagnosed with NAFLD, based on liver biopsy analysis
      through 2002 and followed through 2011. Patients were assigned to mild-,
      intermediate-, or high-risk groups based on cutoff values for 2 of the following:
      NAFLD fibrosis score, aspartate aminotransferase/platelet ratio index, FIB-4
      score, and BARD score. Outcomes included liver-related complications and death or
      liver transplantation. We used multivariate Cox proportional hazard regression
      analysis to adjust for relevant variables and calculate adjusted hazard ratios
      (aHRs). RESULTS: During a median follow-up period of 104.8 months (range, 3-317
      months), 14% of patients developed liver-related events and 13% died or underwent
      liver transplantation. The aHRs for liver-related events in the intermediate-risk
      and high-risk groups, compared with the low-risk group, were 7.7 (95% confidence
      interval [CI]: 1.4-42.7) and 34.2 (95% CI: 6.5-180.1), respectively, based on
      NAFLD fibrosis score; 8.8 (95% CI: 1.1-67.3) and 20.9 (95% CI: 2.6-165.3) based
      on the aspartate aminotransferase/platelet ratio index; and 6.2 (95% CI: 1.4
      27.2) and 6.6 (95% CI: 1.4-31.1) based on the BARD score. The aHRs for death or
      liver transplantation in the intermediate-risk and high-risk groups compared with
      the low-risk group were 4.2 (95% CI: 1.3-13.8) and 9.8 (95% CI: 2.7-35.3),
      respectively, based on the NAFLD fibrosis scores. Based on aspartate
      aminotransferase/platelet ratio index and FIB-4 score, only the high-risk group
      had a greater risk of death or liver transplantation (aHR = 3.1; 95% CI: 1.1-8.4
      and aHR = 6.6; 95% CI: 2.3-20.4, respectively). CONCLUSIONS: Simple noninvasive
      scoring systems help identify patients with NAFLD who are at increased risk for
      liver-related complications or death. NAFLD fibrosis score appears to be the best
      indicator of patients at risk, based on HRs. The results of this study require
      external validation.

PMID- 23860503
TI  - Analysis and detection of the chemical constituents of Radix Polygalae and their
      metabolites in rats after oral administration by ultra high-performance liquid
      chromatography coupled with electrospray ionization quadrupole time-of-flight
      tandem mass spectrometry.
AB  - Radix Polygalae (RP), the dried root of Polygala tenuifolia Willd., is a well
      known traditional Chinese medicine to mediate sedative, antipsychotic, cognitive
      improving, neuroprotective, and anti-inflammatory therapeutic effects on the
      central nervous system. In this work, ultra high-performance liquid
      chromatography coupled with electrospray ionization quadrupole time-of-flight
      tandem mass spectrometry (UHPLC/ESI-Q-TOF-MS/MS) was established for the
      separation and characterization of the chemical constituents in Radix Polygalae
      and their metabolites in rat plasma and urine after oral administration. Samples
      were separated on an Agilent Zorbax Eclipse Plus-C18 column (100mm*2.1mm, 1.8MUm)
      with 0.1% formic acid aqueous solution and acetonitrile as the mobile phase under
      gradient conditions. Overall, 50 compounds were characterized from the RP, 9 of
      which are to our knowledge reported for the first time. In vivo, 10 components
      and 2 metabolites were observed in rat plasma, and 27 components and 7
      metabolites were detected in rat urine. The results from this work improve our
      understanding on the chemical constituents of RP and their metabolic profiling. 

PMID- 23860504
TI  - When do essential tremor patients develop head tremor? Influences of age and
      duration and evidence of a biological clock.
AB  - BACKGROUND: Essential tremor (ET) is a chronic, progressive neurological disease.
      Head (neck) tremor may eventually develop in as many as 30-60% of patients, yet
      it is unclear why. Is its appearance merely a function of advancing disease
      duration? Alternatively, is patient age a primary factor? The latter would argue
      for the presence of a biological clock that is important for the expression of
      this clinical feature of ET. METHODS: A total of 363 ET patients were enrolled in
      a cross-sectional, clinical-epidemiological study. Each ET patient underwent a 20
      min videotaped neurological examination which included an assessment of the
      presence/absence of head tremor. RESULTS: Head tremor was present on examination
      in 140 (38.6%) patients. Young patients, even with longer-duration tremor, rarely
      had head tremor: 2/27 (7.4%) patients<40 years old with tremor duration>=10 years
      had head tremor versus 121/283 (42.8%) older patients (>60 years old) with tremor
      duration>=10 years (p<0.001). In a multivariate logistic regression analysis,
      while head tremor was associated with age (p<0.001) it was not independently
      associated with tremor duration (p=0.26); interestingly, it was associated with
      gender in that model (p<0.001). With the exception of 1 patient, head tremor did
      not begin before the age of 36. CONCLUSIONS: Data suggest that the appearance of
      head tremor in ET depends on a biological factor that is intrinsic to the patient
      (i.e. age) and is not a clear consequence of advancing disease duration.

PMID- 23860505
TI  - Nature of spatial coupling in children with and without developmental
      coordination disorder in ball catching.
AB  - The nature of intra- and interlimb (bimanual) coordination was examined in ten
      boys with (M = 10.5 years, SD = 1.0) and without DCD (M = 10.8 years, SD = .9) in
      a two-handed catching task. Children with developmental coordination disorder
      (DCD) caught significantly fewer balls (MDCD = 56%, SD = 17.6 vs. MnoDCD = 93%,
      SD = 7.5), and both groups solved the "degrees of freedom problem" differently at
      intralimb level of coordination. Typically developing children coupled and
      decoupled the respective spatial relations, whereas the majority of children with
      DCD segmented their actions. At interlimb level, both groups exhibited a
      comparable degree of spatial symmetry. However, individual profiles also showed
      that children with varying degrees of movement issues exhibited movement patterns
      that were qualitatively and functionally diverse. Overall, in the context of
      previous research on interlimb coordination it appears that spatial, in addition
      to temporal organization, may be jeopardized in at least some children with DCD. 

PMID- 23860506
TI  - Young Athletes program: impact on motor development.
AB  - This study examined the effectiveness of the Young Athletes program to promote
      motor development in preschool-aged children with disabilities. In the study, 233
      children were randomly assigned to a control group or the Young Athletes (YA)
      intervention group which consisted of 24 motor skill lessons delivered 3 times
      per week for 8 weeks. Hierarchical Linear Modeling (HLM) showed that children who
      participated in the YA intervention exhibited mean gains of 7-9 months on the
      Peabody Developmental Motor Subscales (PDMS) compared with mean gains of 3-5
      months for the control group. Children in the YA intervention also exhibited
      significant gains on the gross motor subscale of the Vineland Teacher Rating Form
      (VTRF). Teachers and parents reported benefits for children not only in specific
      motor skills, but also kindergarten readiness skills and social/play skills. The
      necessity for direct and intentional instruction of motor skills, as well as the
      challenges of involving families in the YA program, are discussed. 

PMID- 23860507
TI  - Three frameworks to predict physical activity behavior in middle school inclusive
      physical education: a multilevel analysis.
AB  - The purpose of this study was to examine three frameworks, (a) process-product,
      (b) student mediation, and (c) classroom ecology, to understand physical activity
      (PA) behavior of adolescents with and without disabilities in middle school
      inclusive physical education (PE). A total of 13 physical educators teaching
      inclusive PE and their 503 students, including 22 students with different
      disabilities, participated in this study. A series of multilevel regression
      analyses indicated that physical educators' teaching behavior and students'
      implementation intentions play important roles in promoting the students' PA in
      middle school inclusive PE settings when gender, disability, lesson content,
      instructional model, and class location are considered simultaneously. The
      findings suggest that the ecological framework should be considered to
      effectively promote PA of adolescents with and without disabilities in middle
      school PE classes. 

PMID- 23860508
TI  - The relationship of motor skills and social communicative skills in school-aged
      children with autism spectrum disorder.
AB  - Motor skill deficits are present and persist in school-aged children with autism
      spectrum disorder (ASD; Staples & Reid, 2010). Yet the focus of intervention is
      on core impairments, which are part of the diagnostic criteria for ASD, deficits
      in social communication skills. The purpose of this study is to determine whether
      the functional motor skills, of 6- to 15-year-old children with high-functioning
      ASD, predict success in standardized social communicative skills. It is
      hypothesized that children with better motor skills will have better social
      communicative skills. A total of 35 children with ASD between the ages of 6-15
      years participated in this study. The univariate GLM (general linear model)
      tested the relationship of motor skills on social communicative skills holding
      constant age, IQ, ethnicity, gender, and clinical ASD diagnosis. Object-control
      motor skills significantly predicted calibrated ASD severity (p < .05). Children
      with weaker motor skills have greater social communicative skill deficits. How
      this relationship exists behaviorally, needs to be explored further. 

PMID- 23860509
TI  - Public scholarship and the role for injury practitioners.

PMID- 23860510
TI  - Exploring the limits of community detection strategies in complex networks.
AB  - The characterization of network community structure has profound implications in
      several scientific areas. Therefore, testing the algorithms developed to
      establish the optimal division of a network into communities is a fundamental
      problem in the field. We performed here a highly detailed evaluation of community
      detection algorithms, which has two main novelties: 1) using complex closed
      benchmarks, which provide precise ways to assess whether the solutions generated
      by the algorithms are optimal; and, 2) A novel type of analysis, based on
      hierarchically clustering the solutions suggested by multiple community detection
      algorithms, which allows to easily visualize how different are those solutions.
      Surprise, a global parameter that evaluates the quality of a partition, confirms
      the power of these analyses. We show that none of the community detection
      algorithms tested provide consistently optimal results in all networks and that
      Surprise maximization, obtained by combining multiple algorithms, obtains quasi
      optimal performances in these difficult benchmarks. 

PMID- 23860511
TI  - Labware, lab supplies, and microplates.

PMID- 23860513
TI  - [Recommendations for the treatment of heart failure : What's new?].
AB  - Treatment escalation of chronic systolic heart failure depends on left
      ventricular function and symptoms of the patients. In symptomatic patients with
      severely reduced left ventricular function (ejection fraction <= 30 %), the
      following therapeutic approaches are recommended: (1) angiotensin-converting
      enzyme (ACE) inhibitors (angiotensin receptor blocker in case of ACE inhibitor
      intolerance); (2) beta-blockers; (3) mineralocorticoid receptor antagonists; (4)
      diuretics in case of signs and symptoms of congestion; (5) digitalis, in
      particular in patients with atrial fibrillation; (6) ivabradine in patients with
      sinus rhythm and a heart rate >= 75/min; (7) an implantable cardioverter
      defibrillator (ICD); (8) in case of left bundle branch block or wide QRS complex,
      cardiac resynchronization therapy (CRT; in most cases in combination with an
      implantable cardioverter defibrillator); (9) intravenous administration of iron
      in case of iron deficiency; (10) exercise training should be strongly recommended
      in patients with stable heart failure. 

PMID- 23860514
TI  - [Multiple myeloma].
AB  - Multiple myeloma (MM) is a cancer originating from terminally differentiated B
      lymphocytes, the plasma cells and is classified as a B cell non-Hodgkin lymphoma.
      As clonal plasma cells secrete immunoglobulin molecules (lacking antigenic
      specificity), an "M component" can incidentally be detected. Besides intact
      immunoglobulin molecules, free light chains can be produced. Although there is no
      specific treatment for monoclonal gammopathy of undetermined significance (MGUS),
      which is the defined as the presence of clonal bone marrow plasma cells and low
      levels (serum and/or urine) of the M component, it should be followed up in
      affected individuals. The symptoms of MM are numerous and often nonspecific.
      Diagnosis includes the quantification of monoclonal proteins in serum and urine,
      blood count, electrolytes and renal function, imaging of the skeleton and bone
      marrow puncture. The cornerstone of therapy includes melphalan- or
      cyclophosphamide-based regimens incorporating one of the "novel drugs" (i.e.
      bortezomib, thalidomide, or lenalidomide). 

PMID- 23860515
TI  - Differential effects of professional leaders on health care teams in chronic
      disease management groups.
AB  - BACKGROUND: Leadership by health care professionals is likely to vary because of
      differences in the social contexts within which they are situated, socialization
      processes and societal expectations, education and training, and the way their
      professions define and operationalize key concepts such as teamwork,
      collaboration, and partnership. This research examines the effect of the nurse
      and physician leaders on interdependence and encounter preparedness in chronic
      disease management practice groups. PURPOSE: The aim of this study was to examine
      the effect of complementary leadership by nurses and physicians involved in
      jointly producing a health care service on care team functioning. METHODOLOGY:
      The design is a retrospective observational study based on survey data. The unit
      of analysis is heart failure care groups in U.S. Veterans Health Administration
      medical centers. Survey and administrative data were collected in 2009 from 68
      Veterans Health Administration medical centers. Key variables include nurse and
      physician leadership, interdependence, psychological safety, coordination, and
      encounter preparedness. Reliability and validity of survey measures were assessed
      with exploratory factor analysis and Cronbach alphas. Multivariate analyses
      tested hypotheses. FINDINGS: Professional leadership by nurses and physicians is
      related to encounter preparedness by different paths. Nurse leadership is
      associated with greater team interdependence, and interdependence is positively
      associated with respect. Physician leadership is positively associated with
      greater psychological safety, respect, and shared goals but is not associated
      with interdependence. Respect is associated with involvement in learning
      activities, and shared goals are associated with coordination. Coordination and
      involvement in learning activities are positively associated with encounter
      preparedness. PRACTICE IMPLICATIONS: By focusing on increasing interdependence
      and a constructive climate, nurse and physician leaders have the opportunity to
      increase care coordination and involvement in learning activities.

PMID- 23860518
TI  - TiO2/graphene sandwich paper as an anisotropic electrode for high rate lithium
      ion batteries.
AB  - We designed an anisotropic electrode, in which Li(+) ion insertion and diffusion
      are anisotropic, by controlled growth of TiO2 nanosheets parallel to the surface
      of graphene paper. The anisotropic electrode gives a gravimetric capacity of 112
      mA h g(-1) at an ultra-high rate of 100 C (corresponding to 36 s of charge
      discharge), 3 times higher than that of a referenced isotropic electrode. The
      results indicate that such an anisotropic electrode can be useful in the search
      for high-power lithium ion batteries. 

PMID- 23860519
TI  - The NQO1 polymorphism C609T (Pro187Ser) and cancer susceptibility: a
      comprehensive meta-analysis.
AB  - BACKGROUND: Evidence is increasingly emerging about multiple roles for the
      NAD(P)H quinone oxidoreductase 1 enzyme in cancer. The C609T (rs1800566,
      Pro187Ser) null polymorphism of the NQO1 gene contributes significantly to the
      variation in enzymatic activity across different populations. NQO1 C609T
      polymorphism was thoroughly investigated with respect to cancer susceptibility.
      The results were inconsistent partly due to low sample sizes. The aim of the
      present work was to perform a meta-analysis to assess association for all common
      cancer sites separately and in combination. METHODS: Our meta-analysis involved
      92 studies including 21,178 cases and 25,157 controls. Statistical analysis
      involved individual cancer sites and the combined cancer risk. Association was
      tested under different genetic models. RESULTS: We found a statistically
      significant association between the variant T allele and overall cancer risk in
      the worldwide population (for the TT vs CC model, OR=1.18 (1.07-1.31), P=0.002,
      I2=36%). Stratified analysis revealed that this association was largely
      attributed to the Caucasian ethnicity (for the TT vs CC model, OR=1.28 (1.12
      1.46), P=0.0002, I2=1%). Stratification by tumour site showed significant
      association for bladder cancer in the worldwide population (for the TT vs CC
      model, OR=1.70 (1.17-2.46), P=0.005, I2=0%), and in the Asian population (for the
      TT vs CC model, 1.48 (1.14-1.93), P=0.003, I2=16%). Positive association was also
      found for gastric cancer in the worldwide population under the dominant model
      (OR=1.34 (1.09-1.65), P=0.006, I2=15%). CONCLUSION: Our results indicate that the
      C609T polymorphism of the NQO1 gene is an important genetic risk factor in
      cancer.

PMID- 23860520
TI  - Combined effects of goserelin and tamoxifen on estradiol level, breast density,
      and endometrial thickness in premenopausal and perimenopausal women with early
      stage hormone receptor-positive breast cancer: a randomised controlled clinical
      trial.
AB  - BACKGROUND: This study is to investigate the effects of geserelin+tamoxifen (TAM)
      on estradiol level, breast density (BD), endometrial thickness (ET), and blood
      lipids in premenopausal and perimenopausal women with hormone receptor-positive
      early-stage breast cancer. METHODS: This study recruited 110 premenopausal and
      perimenopausal patients with hormone receptor-positive early-stage breast cancer
      between 22 June 2008 and 31 December 2009 and randomly assigned them to receive
      either goserelin plus TAM or TAM alone for 1.5 years. Blood levels of sex
      hormones and lipids and ET were determined at 0, 3, 6, 12, and 18 months.
      Contralateral BD was also measured at 0, 12, and 18 months. RESULTS: Five
      participants dropped out of the goserelin plus TAM group, and two participants
      dropped out of the TAM-alone group before initiation of endocrine therapy. The
      rest of patients received scheduled treatment and 3 years of median follow-up. No
      serious adverse effects were observed, and only two local recurrences have been
      observed in these patients. Estradiol level and BD were lower in the goserelin
      plus TAM group than in the TAM-alone group (P<0.05). The endometrium in the
      goserelin plus TAM group was significantly thinner than that in the TAM-alone
      group (P<0.05), and women in the TAM-alone group exhibited endometrial thickening
      over the course of the study. Furthermore, no significant differences in blood
      lipid levels were reported between the two groups. CONCLUSION: The data from the
      current study demonstrated that the addition of goserelin to TAM results in
      downregulation of estradiol level, followed by significant reduction in BD and ET
      in premenopausal and perimenopausal women with hormone receptor-positive breast
      cancer, which may eventually lead to better outcome in these patients.

PMID- 23860521
TI  - Inversion-mediated gene fusions involving NAB2-STAT6 in an unusual malignant
      meningioma.
AB  - BACKGROUND: Meningiomas are the most common primary intracranial tumours, with
      ~3% meeting current histopathologic criteria for malignancy. METHODS: In this
      study, we explored the transcriptome of meningiomas using RNA-Seq. RESULTS:
      Inversion-mediated fusions between two adjacent genes, NAB2 and STAT6, were
      detected in one malignant tumour, creating two novel in-frame transcripts that
      were validated by RT-PCR and Sanger sequencing. CONCLUSION: Gene fusions of NAB2
      STAT6 were recently implicated in the pathogenesis of solitary fibrous tumours;
      our study suggested that similar fusions may also have a role in a malignant
      meningioma with unusual histopathologic features.

PMID- 23860522
TI  - Pigmentation-related phenotypes and risk of prostate cancer.
AB  - BACKGROUND: Solar ultraviolet radiation exposure has been inversely related to
      prostate cancer incidence and mortality, possibly mediated through vitamin D
      status. Pigmentation-related traits influence endogenous vitamin D synthesis and
      may alter risk of prostate cancer. METHODS: We examined prostate cancer in
      relation to hair and eye colour, and skin phototype in the Alpha-Tocopherol, Beta
      Carotene Cancer Prevention Study cohort. Incident cancer was diagnosed in 1982
      out of 20 863 men. Multivariable hazard ratios (HRs) and 95% confidence intervals
      (CIs) were estimated from Cox proportional hazards models. RESULTS: Prostate
      cancer risk did not differ by eye colour or skin phototype. Men with naturally
      red hair were significantly less likely to develop prostate cancer (HR=0.46, 95%
      CI 0.24-0.89) than men with light brown hair (reference). CONCLUSION: The red
      hair phenotype, which results from polymorphisms in the melanocortin-1-receptor
      (MC1R) gene, is associated with lower risk of prostate cancer. This pigmentation
      related trait may influence prostate cancer development either directly, through
      genetic effects or regulatory mechanisms related to MC1R, another nearby gene, or
      other pigmentation genes, or indirectly, through associations with other
      exposures such as sunlight or vitamin D status.

PMID- 23860523
TI  - Do metastatic colorectal cancer patients who present with late relapse after
      curative surgery have a better survival?
AB  - BACKGROUND: Patients who relapse after potentially curative surgery for
      colorectal cancer tend to relapse within 5 years. There is, however, a group of
      patients who relapse beyond 5 years after resection and this late relapsing group
      may have a different behaviour and prognosis. METHODS: We analysed data from a
      prospective population-based registry to compare the characteristics and survival
      of relapsed patients with metachronous mCRC. Patients were categorised into
      relapse at <2, 2-5 and >5 years following their initial surgery. Univariate log
      rank tests and multivariate Cox regression was performed to determine whether
      time to relapse (TTR) and other factors were associated with overall survival
      (OS). RESULTS: A total of 750 metachronous mCRC patients were identified. In all,
      56% relapsed <=2 years, 32.4% at 2-5 years and 11.6% >5 years. Median survival
      time from the time of diagnosis of mCRC for the three groups was 17.6, 26.1 and
      27.5 months, respectively. Short TTR (<2 years) was significantly associated with
      survival (HR=0.75, 95% confidence interval (CI)=0.60-0.93 and HR=0.73, 95%
      CI=0.53-1.01, respectively, for 2-5 and >5 years vs <2 years, P<0.05). However,
      there was no significant difference in survival between patients who relapsed at
      5 years or later compared with those who relapsed between 2 and 5 years (HR=0.98,
      95% CI=0.69-1.38, P=0.90). CONCLUSION: TTR within 2 years is an independent
      predictor of shorter survival time for mCRC patients who experience a relapse.
      These data do not support the hypothesis that patients who have late relapse late
      (>5 years) have a 'better' biology or survival compared with patients with a TTR
      of 2-5 years.

PMID- 23860524
TI  - Anthropometric measures and epithelial ovarian cancer risk among Chinese women:
      results from the Shanghai Women's Health Study.
AB  - BACKGROUND: Studies of anthropometric measures and ovarian cancer risk have
      predominantly included women of European descent with mixed findings. METHODS:
      Data from the prospective Shanghai Women's Health Study (SWHS) were used to
      evaluate associations between anthropometric measures and risk of epithelial
      ovarian cancer (EOC). Hazard ratios (HRs) and 95% confidence intervals (CIs) were
      estimated by Cox proportional hazards regression. RESULTS: A total of 152 EOC
      cases occurred among 70 258 women. Increasing quartiles of weight, hip
      circumference, and weight gain during adulthood were associated with
      significantly increased EOC risks. Body mass index (BMI) was also associated;
      overweight (25BMI<29.99) and obese women (BMI?30.0) had significantly increased
      risks (HR: 1.49, 95% CI: 1.05, 2.13, and HR: 2.42, 95% CI: 1.37, 4.28,
      respectively). No significant associations were observed for height, waist
      circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHER).
      CONCLUSION: Results from this large prospective study of Chinese women support
      the hypothesis that general adiposity contributes to the aetiology of ovarian
      cancer.

PMID- 23860525
TI  - Long-term and baseline recreational physical activity and risk of endometrial
      cancer: the California Teachers Study.
AB  - BACKGROUND: Physical activity may be associated with decreasing endometrial
      cancer risk; it remains unclear whether the association is modified by body size.
      METHODS: Among 93 888 eligible California Teachers Study participants, 976 were
      diagnosed with incident endometrial cancer between 1995-1996 and 2007. Cox
      proportional hazards regression methods were used to estimate relative risks
      (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with
      long-term (high school through age 54 years) and baseline (3 years prior to
      joining the cohort) strenuous and moderate recreational physical activity,
      overall and by body size. RESULTS: Increased baseline strenuous recreational
      physical activity was associated with decreased endometrial cancer risk
      (Ptrend=0.006) with approximately 25% lower risk among women exercising >3 h per
      week per year than among those exercising <1/2 h per week per year (RR, 0.76; 95%
      CI, 0.63-0.92). This inverse association was observed among overweight/obese
      women (body mass index >=25 kg m(-2); Ptrend=0.006), but not among thinner women
      (Ptrend=0.12). Baseline moderate activity was associated with lower risk among
      overweight/obese women. CONCLUSION: Increasing physical activity, particularly
      strenuous activity, may be a lifestyle change that overweight and obese women can
      implement to reduce their endometrial cancer risk.

PMID- 23860526
TI  - VEGF-A polymorphisms predict progression-free survival among advanced castration
      resistant prostate cancer patients treated with metronomic cyclophosphamide.
AB  - BACKGROUND: No data are available on the pharmacogenetics of metronomic
      chemotherapy in prostate cancer. The aim of this study was to evaluate the
      association between VEGF-A sequence variants and prostate-specific antigen (PSA)
      progression, progression-free survival (PFS) and overall survival (OS), in
      advanced castration-resistant prostate cancer patients treated with metronomic
      cyclophosphamide (CTX), celecoxib and dexamethasone. METHODS: Forty-three
      patients were enrolled, and genomic DNA was extracted. VEGF-A gene SNPs (
      2578A/C, -634C/G, +936C/T) were analysed using TaqMan PCR assays. Hardy-Weinberg
      equilibrium was tested for each SNP, and genetic effects were evaluated by
      Fisher's exact test. PFS and OS were analysed with GraphPad Prism software, using
      the product limit method of Kaplan and Meier, and comparing survival curves using
      both the log-rank test and the Gehan-Wilcoxon test. We used Bonferroni correction
      to account for multiple testing, and a two-tailed P-value of <0.017 was
      considered statistically significant. RESULTS: Overall, 20 patients (46%)
      experienced a reduction in PSA levels from baseline and, among them, 14 (32%)
      showed a confirmed PSA >=50% decrease. In non-responders, the -2578CC genotype
      was more frequent (18.60% vs 2.33% in responders; P=0.0212) whereas the -634CC
      genotype frequency was 22.73% vs 0% in responders (P=0.0485). With regard to PFS,
      patients harbouring the -634CC genotype had a median PFS of 2.2 months whereas
      patients with the genotype -634CG/GG had a median PFS of 6.25 months (P=0.0042).
      CONCLUSION: The -634CC genotype is significantly associated with a shorter PFS in
      patients treated with a metronomic CTX schedule.

PMID- 23860527
TI  - Sequelae and survivorship in patients treated with (131)I-MIBG therapy.
AB  - BACKGROUND: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) has been in therapeutic
      use since 1980s. Newer treatment modalities are emerging for neuroendocrine
      tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet
      have adequate long-term follow-up to determine their longer term efficacy and
      sequelae. METHODS: Fifty-eight patients with metastatic NETs and CCTs who had
      received (131)I-MIBG therapy between 2000 and 2011 were analysed. Survival and
      any long-term haematological or renal sequelae were investigated. RESULTS: In the
      NET group, the overall median survival and median survival following the
      diagnosis of metastatic disease was 124 months. The median survival following the
      commencement of (131)I-MIBG was 66 months. For the CCT group, median survival had
      not been reached. The 5-year survival from diagnosis and following the diagnosis
      of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5
      year survival following the commencement of (131)I-MIBG therapy was 68%. Thirty
      two patients had long-term haematological sequelae: 5 of these 32 patients
      developed haematological malignancies. Two patients developed a mild
      deterioration in renal function. CONCLUSION: Long follow up of (131)I-MIBG
      therapy reveals a noteable rate of bone marrow toxicities and malignancy and long
      term review of all patients receiving radionuclide therapies is recommended.

PMID- 23860528
TI  - Cancer of unknown primary: a population-based analysis of temporal change and
      socioeconomic disparities.
AB  - BACKGROUND: Cancer of unknown primary (CUP) is the fourth most common cause of
      cancer death. With advanced diagnostics and treatments, we investigated the
      proportion of cancers diagnosed as CUP, treatment outcomes and association with
      socioeconomic disparities. METHODS: We analysed trends in CUP diagnosis and
      outcome within the Surveillance, Epidemiology, and End Results registry between
      1973 and 2008. RESULTS: The percentage of all cancers diagnosed as CUP has
      decreased over time comprising <2% of cancers since 2007. A higher proportion of
      CUP was diagnosed in the elderly, females, blacks and residents of less affluent
      or less educated counties. Median survival of all CUP patients was 3 months, with
      no improvement over time. The 5-year survival significantly improved in those
      with squamous histology (squamous cell carcinoma; SCC) but only marginally in non
      SCC. Factors associated with a longer survival on multivariate analysis included
      white race; female; <65 years old; most recent decade at diagnosis; SCC; married;
      a histological diagnosis; and treatment with radiotherapy (all P<0.001). Despite
      the improvement in survival with radiotherapy, its use was less frequent in
      females and blacks. CONCLUSION: The percentage of cancers diagnosed as CUP is
      decreasing but prognosis remains poor, particularly in non-SCC CUP. However,
      significant socioeconomic disparities exist in diagnosis and survival, suggesting
      inequalities in access to diagnostic investigations and treatment.

PMID- 23860529
TI  - Development of an imaging-guided CEA-pretargeted radionuclide treatment of
      advanced colorectal cancer: first clinical results.
AB  - BACKGROUND: Radiolabelled antibody targeting of cancer is limited by slow blood
      clearance. Pretargeting with a non-radiolabelled bispecific monoclonal antibody
      (bsMAb) followed by a rapidly clearing radiolabelled hapten peptide improves
      tumour localisation. The primary goals of this first pretargeting study in
      patients with the anti-CEACAM5 * anti-hapten (HSG) bsMAb, TF2, and the
      radiolabelled hapten-peptide, IMP288, were to assess optimal pretargeting
      conditions and safety in patients with metastatic colorectal cancer (CRC).
      METHODS: Different dose schedules were studied in four cohorts of five patients:
      (1) shortening the interval between the bsMAb and peptide administration (5 days
      vs 1 day), (2) escalating the TF2 dose (from 75 to 150 mg), and (3) reducing the
      peptide dose (from 100 to 25 MUg). After confirmation of tumour targeting by
      (111)In-IMP288, patients were treated with a bsMAb/(177)Lu-IMP288 cycle. RESULTS:
      Rapid and selective tumour targeting of the radiolabelled peptide was visualised
      within 1 h, with high tumour-to-tissue ratios (>20 at 24 h). Improved tumour
      targeting was achieved with a 1-day interval between the administration of the
      bsMAb and the peptide and with the 25-MUg peptide dose. High (177)Lu-IMP288 doses
      (2.5-7.4 GBq) were well tolerated, with some manageable TF2 infusion reactions,
      and transient grades 3-4 thrombocytopaenia in 10% of the patients who received
      (177)Lu-IMP288. CONCLUSION: This phase I study demonstrates for the first time
      that pretargeting with bsMAb TF2 and radiolabelled IMP288 in patients with CEA
      expressing CRC is feasible and safe. With this pretargeting method, tumours are
      specifically and rapidly targeted.

PMID- 23860530
TI  - A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking
      women younger than 70 years receiving moderately emetogenic chemotherapy.
AB  - BACKGROUND: We evaluated the efficacy of aprepitant plus granisetron and an
      increased dose of dexamethasone in selected patients undergoing moderately
      emetogenic chemotherapy (MEC). METHODS: Nondrinking women <70 years undergoing
      MEC were randomly assigned to aprepitant (day 1, 125 mg; days 2 and 3, 80 mg) or
      placebo. Dexamethasone on days 1-3 was 12, 4, and 4 mg with aprepitant and 20, 8,
      and 8 mg with placebo. The primary end point was complete response (CR; no emesis
      or rescue therapy) during 120 h of the first cycle. Logistic regression analysis
      was performed to identify predictors of overall CR. RESULTS: Of the 94 patients
      enrolled, 91 were assessable. Most received carboplatin-based chemotherapy. In
      the aprepitant (n=45) and placebo (n=46) groups, the overall, acute (day 1), and
      delayed (days 2-5) CR rates were 62% and 52%, 98% and 96%, and 62% and 52%,
      respectively. Although not statistically significant, the overall CR rate was 10%
      higher in the aprepitant group. Both regimens were well tolerated. On
      multivariate analysis, advanced ovarian cancer (OR, 0.26 (0.10-0.72)) was
      independently associated with a lower CR. CONCLUSION: Even with an increased dose
      of dexamethasone, aprepitant seemed more effective than placebo in these selected
      patients undergoing MEC; however, delayed phase management remains a significant
      problem.

PMID- 23860531
TI  - Increased risk of second malignancies in chronic lymphocytic leukaemia patients
      as compared with follicular lymphoma patients: a Canadian population-based study.
AB  - BACKGROUND: Chronic lymphocytic leukaemia (CLL) patients have an increased risk
      of other malignancies. This may be due to surveillance bias, treatment or
      immunosuppression. METHODS: Cohort study of 612 consecutively diagnosed CLL
      patients in a Canadian province, with comparisons to follicular lymphoma (FL)
      patients. RESULTS: Treated CLL patients had a 1.7-fold increased risk of second
      cancers compared with untreated CLL patients. As compared with untreated FL
      patients, untreated CLL patients had a two-fold increased incidence of second
      malignancies. CONCLUSION: Chronic lymphocytic leukaemia patients have an inherent
      predisposition to second cancers and the incidence is further increased by
      treatment.

PMID- 23860532
TI  - KIT, NRAS and BRAF mutations in sinonasal mucosal melanoma: a study of 56 cases.
AB  - BACKGROUND: Mucosal melanomas in the head and neck region are most frequently
      located in the nasal cavity and paranasal sinuses. Sinonasal mucosal melanoma
      (SNMM) comprises <1% of all melanomas. The aim was to determine the KIT, NRAS and
      BRAF mutation frequencies in a large series of primary SNMMs. METHODS: Laser
      capture microdissection was used to isolate tumour cells from 56 formalin-fixed
      paraffin-embedded tumours. The tumour cells were screened for KIT, NRAS and BRAF
      mutations by direct sequencing. RESULTS: Overall, 21% (12 out of 56) of SNMMs
      harboured KIT, NRAS or BRAF mutations. Mutations in these oncogenes occurred in a
      mutually exclusive manner. Both KIT and BRAF mutations were identified at a
      similar frequency of 4% each (2 out of 56), whereas NRAS mutations were detected
      in 14% (8 out of 56) of the SNMMs. Four of the NRAS mutations were located in
      exon 1. Mutations in these oncogenes were significantly more common in melanomas
      located in the paranasal sinuses than in nasal cavity (P=0.045). In a
      multivariate analysis, patients with melanomas in the nasal cavity had a
      significantly better overall survival than those with tumours in the paranasal
      sinuses (P=0.027). CONCLUSION: Our findings show that KIT and BRAF mutations,
      which are accessible for present targeted therapies, are only rarely present in
      SNMMs, whereas NRAS mutations seem to be relatively more frequent. The data show
      that majority of SNMMs harbour alterations in genes other than KIT, NRAS and
      BRAF.

PMID- 23860533
TI  - Patients' and urologists' preferences for prostate cancer treatment: a discrete
      choice experiment.
AB  - BACKGROUND: Patients' preferences are important for shared decision making.
      Therefore, we investigated patients' and urologists' preferences for treatment
      alternatives for early prostate cancer (PC). METHODS: A discrete choice
      experiment was conducted among 150 patients who were waiting for their biopsy
      results, and 150 urologists. Regression analysis was used to determine patients'
      and urologists' stated preferences using scenarios based on PC treatment modality
      (radiotherapy, surgery, and active surveillance (AS)), and risks of urinary
      incontinence and erectile dysfunction. RESULTS: The response rate was 110 out of
      150 (73%) for patients and 50 out of 150 (33%) for urologists. Risk of urinary
      incontinence was an important determinant of both patients' and urologists'
      stated preferences for PC treatment (P<0.05). Treatment modality also influenced
      patients' stated preferences (P<0.05), whereas the risk of erectile dysfunction
      due to radiotherapy was mainly important to urologists (P<0.05). Both patients
      and urologists preferred AS to radical treatment, with the exception of patients
      with anxious/depressed feelings who preferred radical treatment to AS.
      CONCLUSION: Although patients and urologists generally may prefer similar
      treatments for PC, they showed different trade-offs between various specific
      treatment aspects. This implies that urologists need to be aware of potential
      differences compared with the patient's perspective on treatment decisions in
      shared decision making on PC treatment.

PMID- 23860534
TI  - Individual risk profiling for breast cancer recurrence: towards tailored follow
      up schemes.
AB  - BACKGROUND: Breast cancer follow-up is not tailored to the risk of locoregional
      recurrences (LRRs) in individual patients or as a function of time. The objective
      of this study was to identify prognostic factors and to estimate individual and
      time-dependent LRR risk rates. METHODS: Prognostic factors for LRR were
      identified by a scoping literature review, expert consultation, and stepwise
      multivariate regression analysis based on 5 years of data from women diagnosed
      with breast cancer in the Netherlands in 2005 or 2006 (n=17,762). Inter-patient
      variability was elucidated by examples of 5-year risk profiles of average-,
      medium-, and high-risk patients, whereby 6-month interval risks were derived from
      regression estimates. RESULTS: Eight prognostic factors were identified: age,
      tumour size, multifocality, gradation, adjuvant chemo-, adjuvant radiation-,
      hormonal therapy, and triple-negative receptor status. Risk profiles of the low-,
      average-, and high-risk example patients showed non-uniform distribution of
      recurrence risks (2.9, 7.6, and 9.2%, respectively, over a 5-year period).
      CONCLUSION: Individual risk profiles differ substantially in subgroups of
      patients defined by prognostic factors for recurrence and over time as defined in
      6-month time intervals. To tailor follow-up schedules and to optimise allocation
      of scarce resources, risk factors, frequency, and duration of follow-up should be
      taken into account.

PMID- 23860535
TI  - Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line
      therapy in malignant pleural mesothelioma.
AB  - BACKGROUND: The aim of this open label phase II study (NCT00407459) was to assess
      the activity of the vascular endothelial growth factor (VEGF) inhibitor
      bevacizumab combined with pemetrexed and carboplatin in patients with previously
      untreated, unresectable malignant pleural mesothelioma (MPM). METHODS: Eligible
      patients received pemetrexed 500 mg m(-2), carboplatin area under the plasma
      concentration-time curve (AUC) 5 mg ml(-1) per minute and bevacizumab 15 mg kg(
      1), administered intravenously every 21 days for six cycles, followed by
      maintenance bevacizumab. The primary end point of the study was progression-free
      survival (PFS). A 50% improvement in median PFS in comparison with standard
      pemetrexed/platinum combinations (from 6 to 9 months) was postulated. RESULTS:
      Seventy-six patients were evaluable for analysis. A partial response was achieved
      in 26 cases (34.2%, 95% CI 23.7-46.0%). Forty-four (57.9%, 95% CI 46.0-69.1%) had
      stable disease. Median PFS and overall survival were 6.9 and 15.3 months,
      respectively. Haematological and non-haematological toxicities were generally
      mild; however, some severe adverse events were reported, including grade 3-4
      fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths
      occurred. CONCLUSION: The primary end point of the trial was not reached.
      However, due to the limitation of a non-randomised phase II design, further data
      are needed before drawing any definite conclusion on the role of bevacizumab in
      MPM.

PMID- 23860537
TI  - Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients
      with non-small-cell lung cancer.
AB  - BACKGROUND: This dose-finding study evaluated lenvatinib, an oral multitargeted
      receptor tyrosine kinase inhibitor, in combination with carboplatin/paclitaxel in
      chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND
      METHODS: Patients received lenvatinib twice daily (BID) with carboplatin (area
      under the curve 6 mg ml(-1) min(-1), day 1)/paclitaxel (200 mg m(-2), day 1)
      every 3 weeks. The initial dose of lenvatinib was 6 mg BID. The primary end point
      was maximum tolerated dose (MTD) of lenvatinib. At the MTD, the cohort was
      expanded by 16 patients. Safety, pharmacokinetics, pharmacodynamics, and
      antitumor effects were evaluated. RESULTS: Twenty-eight patients were treated. At
      6 mg BID, dose-limiting toxicities (DLTs) included febrile neutropenia/gingival
      infection (n=2). No DLTs occurred with 4 mg BID, the recommended MTD for the
      expansion. Common grade 3/4 toxicities included neutropenia, leukopenia,
      hypertension, and thrombocytopenia. The combination had no significant impact on
      individual drug pharmacokinetics. Response rate and median progression-free
      survival were 68% and 9.0 months, respectively, with 4 mg BID. In the plasma
      biomarker analysis, stromal cell-derived factor 1alpha, stem cell factor, and
      granulocyte colony-stimulating factor correlated with antitumor activity.
      CONCLUSION: The MTD for lenvatinib with carboplatin/paclitaxel is 4 mg BID in
      advanced NSCLC patients. This regimen demonstrated manageable tolerability and
      encouraging antitumor activity.

PMID- 23860536
TI  - Targeting tumour energy metabolism potentiates the cytotoxicity of 5
      aminolevulinic acid photodynamic therapy.
AB  - BACKGROUND: Cancerous cells usually exhibit increased aerobic glycolysis,
      compared with normal tissue (the Warburg effect), making this pathway an
      attractive therapeutic target. METHODS: Cell viability, cell number, clonogenic
      assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour
      cells and corresponding primary human mammary epithelial cells (HMEC). RESULTS:
      Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180 mM) or lonidamine
      (300 MUM) with 10 J cm(-2) 5-aminolevulinic acid (ALA) photodynamic therapy (PDT)
      increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24 h, and by 10-fold
      in 9-day clonogenic assays). However, glycolysis inhibition only slightly
      increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of
      9% death after 24 h). The potentiation of PDT cytotoxicity only occurred if the
      glycolysis inhibitors were added after ALA incubation, as they inhibited
      intracellular accumulation of photosensitiser if coincubated with ALA.
      CONCLUSION: As 2DG and lonidamine are already used as cancer chemotherapeutic
      agents, our results are directly translatable to combination therapies with
      existing topical PDT.

PMID- 23860539
TI  - Embedding an electron donor or acceptor into naphtho[2,1-b:3,4-b']dithiophene
      based organic sensitizers for dye-sensitized solar cells.
AB  - An electron donor and acceptor, respectively, is embedded into naphtho[2,1-b:3,4
      b']dithiophene based organic sensitizers to tune their optoelectronic properties.
      The DSSC based on FNE52 containing an auxiliary electron acceptor displays a
      maximum power conversion efficiency of 8.2% and good long-term stability. 

PMID- 23860538
TI  - The evolutionary histories of clinical and environmental SHV beta-lactamases are
      intertwined.
AB  - The rise of antibiotic-resistant pathogens focuses our attention on the source of
      antibiotic resistance genes, on the existence of these genes in environments
      exposed to little or no antibiotics, and on the relationship between resistance
      genes found in the clinic and those encountered in non-clinical settings. Here,
      we address the evolutionary history of a class of resistance genes, the SHV beta
      lactamases. We focus on bla SHV genes isolated both from clinical and non
      clinical sources and show that clinically important resistance determinants arise
      repeatedly from within a diverse pool of bla SHV genes present in the
      environment. While our results argue against the notion of a single common origin
      for all clinically derived bla SHV genes, we detect a characteristic selective
      signature shaping this protein in clinical environments. This clinical signature
      reveals the joint action of purifying and positive selection on specific
      residues, including those known to confer extended-spectrum activity.
      Surprisingly, antibiotic resistance genes isolated from non-clinical-and
      presumably antibiotic-free-settings also experience the joint action of purifying
      and positive selection. The picture that emerges undercuts the notion of a
      separate reservoir of antibiotic resistance genes confined only to clinical
      settings. Instead, we argue for the presence of a single extensive and variable
      pool of antibiotic resistance genes present in the environment. 

PMID- 23860540
TI  - Effect of ceria structural properties on the catalytic activity of Au-CeO2
      catalysts for WGS reaction.
AB  - Two gold based catalysts supported on ceria prepared by different methods (urea
      gelation coprecipitation, UGC, and coprecipitation, CP) have been synthesized and
      tested in the WGS reaction, showing quite different catalytic behaviors.
      Interestingly, the two catalysts have the same gold loading (3 wt% Au was
      inserted by deposition-precipitation) and the FTIR spectroscopy of the adsorbed
      CO revealed the same amount of gold exposed sites. With the aim to elucidate how
      the preparation method affects the properties of the support, a morphological,
      structural and textural characterization has been performed by HRTEM, XRD, BET
      and Raman analyses, as well as FTIR spectroscopy to probe both the Au and the
      support exposed sites. It was found that the UGC method gave rise to an
      enhancement of the defectivity of ceria and to an increase of the reactivity
      under reductive treatment. Further FTIR measurements of adsorbed acetone
      demonstrated the presence of two kinds of Ce(4+) sites with different
      coordination, (CUS) Ce(4+) A and (CUS) Ce(4+) B, on the UGC sample. Such sites
      can influence the catalytic activity, possibly favoring the water dissociation,
      making ceria prepared by UGC a better support for Au catalysts than the CP
      prepared one. 

PMID- 23860541
TI  - Rare occurrence of the JAK1 mutation in acute promyelocytic leukemia patients.

PMID- 23860542
TI  - On dermal exposure assessment.
AB  - Hazardous chemicals may enter the body by inhalation, ingestion, injection or
      dermal absorption. These exposure routes constitute the overall exposure burden
      on the body. Most occupational exposure studies have focused on measurement of
      the concentration of air-borne contaminants and other possible routes of exposure
      are often overlooked.Several studies have already highlighted the importance of
      dermal absorption. However, less development occurred in the assessment of dermal
      exposures to occupational and environmental contaminants compared to air sampling
      techniques.This paper intends to highlight the importance of dermal exposure and
      looks at the methods currently used for its assessment. Advantages and
      disadvantages of each method in the context of occupational dermal exposure
      assessment are also outlined. Dermal exposure models, as an easy-to-use and low
      cost tool to predict dermal uptake, especially when few or no actual data are
      available, are also included in this review. 

PMID- 23860543
TI  - Lung cancer mortality among uranium gaseous diffusion plant workers: a cohort
      study 1952-2004.
AB  - BACKGROUND: 9%-15% of all lung cancers are attributable to occupational
      exposures. Reports are disparate regarding elevated lung cancer mortality risk
      among workers employed at uranium gaseous diffusion plants. OBJECTIVE: To
      investigate whether external radiation exposure is associated with lung cancer
      mortality risk among uranium gaseous diffusion workers. METHODS: A cohort of 6820
      nuclear industry workers employed from 1952 to 2003 at the Paducah uranium
      gaseous diffusion plant (PGDP) was assembled. A job-specific exposure matrix
      (JEM) was used to determine likely toxic metal exposure categories. In addition,
      radiation film badge dosimeters were used to monitor cumulative external ionizing
      radiation exposure. International Classification for Disease (ICD) codes 9 and 10
      were used to identify 147 lung cancer deaths. Logistic and proportional hazards
      regression were used to estimate lung cancer mortality risk. RESULTS: Lung cancer
      mortality risk was elevated among workers who experienced external radiation >3.5
      mrem and employment duration >12 years. CONCLUSION: Employees of uranium gaseous
      diffusion plants carry a higher risk of lung cancer mortality; the mortality is
      associated with increased radiation exposure and duration of employment.

PMID- 23860544
TI  - Teaching emotional intelligence to intensive care unit nurses and their general
      health: a randomized clinical trial.
AB  - BACKGROUND: Emotion and how people manage it is an important part of personality
      that would immensely affect their health. Investigations showed that emotional
      intelligence is significantly related to and can predict psychological health.
      OBJECTIVE: To determine the effect of teaching emotional intelligence to
      intensive care unit nurses on their general health. METHODS: This randomized
      clinical trial (registered as IRCT201208022812N9) was conducted on 52 of 200 in
      intensive care unit nurses affiliated to Shiraz University of Medical Sciences.
      They were recruited through purposeful convenience sampling and then randomly
      categorized into two groups. The intervention group members were trained in
      emotional intelligence. Bar-on emotional intelligence and Goldberg's general
      health questionnaires were administered to each participant before, immediately
      after, and one month after the intervention. RESULTS: While the mean score of
      general health for the intervention group decreased from 25.4 before the
      intervention, to 18.1 immediately after the intervention and to 14.6 one month
      later, for the control group, it increased from 22.0, to 24.2 and to 26.5,
      respectively (p<0.001). CONCLUSION: Teaching emotional intelligence improved the
      general health of intensive care unit nurses.

PMID- 23860545
TI  - Occupational exposure to mercury among workers in a fluorescent lamp factory,
      Quisna Industrial Zone, Egypt.
AB  - BACKGROUND: With the fast growth in the market of fluorescent lamps, particularly
      compact fluorescent light, the associated risk of mercury exposure, which is an
      essential component in all types of fluorescent lamps, has received increasing
      public attention worldwide. Even low doses of mercury are toxic. OBJECTIVE: To
      study the health consequences of occupational exposure to mercury in workers of a
      fluorescent lamp factory. METHODS: In a cross-sectional study 138 workers of a
      fluorescent lamp factory and 151 people who had no occupational exposure to
      mercury (the comparison group) were studied. Environmental study of mercury and
      noise levels was done. For all participants a neurobehavioral test battery was
      administered, spirometry was performed and air conduction audiometry was done.
      Urinary mercury level was also measured for all participants. RESULTS: Prominent
      symptoms among workers exposed to mercury included tremors, emotional lability,
      memory changes, neuromuscular changes, and performance deficits in tests of
      cognitive function. Among the exposed group, the mean urinary mercury level was
      significantly higher in those who had personality changes or had manifestations
      of mercury toxicity. With increasing duration of employment and urinary mercury
      level, the performance of participants in neurobehavioral test battery and
      spirometric parameters deteriorated. CONCLUSION: Neurobehavioral test battery
      must be used for studying subclinical central nervous system dysfunction in those
      with chronic exposure to mercury. The test is especially useful for evaluating
      the severity of mercury effects in epidemiological studies. This study also
      reinforces the need for effective preventive programs for fluorescent lamp
      industry workplaces especially in developing countries with the lowest unhygienic
      work conditions.

PMID- 23860546
TI  - Fitness-for-work assessment of train drivers of Yazd railway, central Iran.
AB  - BACKGROUND: National Transport Commission (NTC) classifies train driving as a
      high-level safety critical job. OBJECTIVE: To assess fitness-for-work among train
      drivers in Yazd, central Iran. METHODS: We evaluated 152 train drivers for their
      fitness for duty. The results were then compared with NTC guidelines. RESULTS:
      63.8% of subjects were fit for duty, 34.2% fit subject to review, and 2.0% were
      temporarily unfit. The most common reason for fit subject to review was a Kessler
      score >19. The prevalence of overweight and obesity was 48.0% and 15.0%,
      respectively. The prevalence of dyslipidemia was 69.7%, diabetes 10.0%, impaired
      fasting glucose 36.0%, and hypertension was 19.0%, respectively. CONCLUSION: Most
      studied train drivers can continue their work safely. The prevalence of some risk
      factors such as overweight and dyslipidemia were high among train drivers. This
      warrants further evaluation and establishment of control programs.

PMID- 23860547
TI  - Intestinal obstruction in acute inhalational toluene 2,4-diisocyanate gas
      toxicity.
AB  - The isocyanates are widely used as precursors of polyurethane products, as well
      as carbamate insecticides. Toluene 2,4-diisocyanate (TDI) is one of the most
      important commercially used isocyanates. Humans may be exposed to TDI by
      inhalation, ingestion, dermal and eye contact. TDI is a powerful irritant to the
      mucosal membranes of the gastrointestinal and respiratory tracts, eyes and the
      skin. Pulmonary manifestations, especially occupational asthma, are the
      predominant manifestations after TDI toxicity. Herein, we present intestinal
      obstruction as an extraordinary manifestation of acute TDI toxicity after
      occupational exposure. TDI toxicity may cause intestinal obstruction. 

PMID- 23860548
TI  - Methyl isocyanate exposure and atypical lymphocytes.

PMID- 23860549
TI  - Assessment of interfractional prostate motion in patients immobilized in the
      prone position using a thermoplastic shell.
AB  - The aim of this study was to evaluate the interfractional prostate motion of
      patients immobilized in the prone position using a thermoplastic shell. A total
      of 24 patients with prostate calcifications detectable using a kilo-voltage X-ray
      image-guidance system (ExacTrac X-ray system) were examined. Daily displacements
      of the calcification within the prostate relative to pelvic bony structures were
      calculated by the ExacTrac X-ray system. The average displacement and standard
      deviation (SD) in each of the left-right (LR), anterior-posterior (AP), and
      superior-inferior (SI) directions were calculated for each patient. Based on the
      results of interfractional prostate motion, we also calculated planning target
      volume (PTV) margins using the van Herk formula and examined the validity of the
      PTV margin of our institute (a 9-mm margin everywhere except posteriorly, where a
      6-mm margin was applied). In total, 899 data measurements from 24 patients were
      obtained. The average prostate displacements +/- SD relative to bony structures
      were 2.8 +/- 3.3, -2.0 +/- 2.0 and 0.2 +/- 0.4 mm, in the SI, AP and LR
      directions, respectively. The required PTV margins were 9.7, 6.1 and 1.4 mm in
      the SI, AP and LR directions, respectively. The clinical target volumes of 21
      patients (87.5%) were located within the PTV for 90% or more of all treatment
      sessions. Interfractional prostate motion in the prone position with a
      thermoplastic shell was equivalent to that reported for the supine position. The
      PTV margin of our institute is considered appropriate for alignment, based on
      bony structures. 

PMID- 23860550
TI  - Adeno-associated Virus-mediated, Mifepristone-regulated Transgene Expression in
      the Brain.
AB  - Gene therapy, in its current configuration, is irreversible and does not allow
      control over transgene expression in case of side effects. Only few regulated
      vector systems are available, and none of these has reached clinical
      applicability yet. The mifepristone (Mfp)-regulated Gene Switch (GS) system is
      characterized by promising features such as being composed of mainly human
      components and an approved small-molecule drug as an inducer. However, it has not
      yet been evaluated in adeno-associated virus (AAV) vectors, neither has it been
      tested for applicability in viral vectors in the central nervous system (CNS).
      Here, we demonstrate that the GS system can be used successfully in AAV vectors
      in the brain, and that short-term induced glial cell line-derived neurotrophic
      factor (GDNF) expression prevented neurodegeneration in a rodent model of
      Parkinson's disease (PD). We also demonstrate repeated responsiveness to the
      inducer Mfp and absence of immunological tissue reactions in the rat brain. Human
      equivalent dosages of Mfp used in this study were lower than those used safely
      for treatment of psychiatric threats, indicating that the inducer could be safely
      applied in patients. Our results suggest that the GS system in AAV vectors is
      well suited for further development towards clinical applicability.Molecular
      Therapy-Nucleic Acids (2013) 2, e106; doi:10.1038/mtna.2013.35; published online
      16 July 2013. 

PMID- 23860551
TI  - Dimeric DNA Aptamer Complexes for High-capacity-targeted Drug Delivery Using pH
      sensitive Covalent Linkages.
AB  - Treatment with doxorubicin (Dox) results in serious systemic toxicities that
      limit effectiveness for cancer treatment and cause long-term health issues for
      cancer patients. We identified a new DNA aptamer to prostate-specific membrane
      antigen (PSMA) using fixed sequences to promote Dox binding and developed dimeric
      aptamer complexes (DACs) for specific delivery of Dox to PSMA(+) cancer cells.
      DACs are stable under physiological conditions and are internalized specifically
      into PSMA(+) C4-2 cells with minimal uptake into PSMA-null PC3 cells. Cellular
      internalization of DAC was demonstrated by confocal microscopy and flow
      cytometry. Covalent modification of DAC with Dox (DAC-D) resulted in a complex
      with stoichiometry ~4:1. Dox was covalently bound in DAC-D using a reversible
      linker that promotes covalent attachment of Dox to genomic DNA following cell
      internalization. Dox was released from the DAC-D under physiological conditions
      with a half-life of 8 hours, sufficient for in vivo targeting. DAC-D was used to
      selectively deliver Dox to C4-2 cells with endosomal release and nuclear
      localization of Dox. DAC-D was selectively cytotoxic to C4-2 cells with similar
      cytotoxicity as the molar equivalent of free-Dox. In contrast, DAC-D displayed
      minimal cytotoxicity to PC3 cells, demonstrating the complex displays a high
      degree of selectivity for PSMA(+) cells. DAC-D displays specificity and stability
      features that may be useful for improved delivery of Dox selectively to malignant
      tissue in vivo.Molecular Therapy-Nucleic Acids (2013) 2, e107;
      doi:10.1038/mtna.2013.37; published online 16 July 2013. 

PMID- 23860553
TI  - The intensity of chair-assisted exercises in cognitively healthy older adults.
AB  - INTRODUCTION: The American College of Sports Medicine prescribes regular
      performance of at least moderate-intensity physical activity for healthy aging.
      This study examined whether 1 session of 30 min of chair-assisted exercises for
      the elderly meets this intensity criterion. METHOD: This cross-sectional study
      included 47 cognitively healthy volunteers (mean age 84 years). During the
      performance of 30 min of chair-assisted exercises the authors determined oxygen
      uptake (VO2), carbon dioxide production, heart rate (HR), and rating of perceived
      exertion (RPE). These measures were expressed as a percentage of the estimated
      maximal VO2 (VO2max) and the estimated maximal HR (HRmax) and estimated as
      metabolic equivalent units (METs). RESULTS: Participants performed chair-assisted
      exercises at 61.0% +/- 14.7% of VO2max, 67.6% +/- 11.3% HRmax, 3.9 +/- 0.9 METs,
      and 13.1 +/- 2.1 RPE. CONCLUSIONS: The intensity of these chair-assisted
      exercises is at least moderate for older adults, which is necessary for healthy
      aging.

PMID- 23860559
TI  - Development of a magnetic biocatalyst useful for the synthesis of ethyloleate.
AB  - Candida antarctica Lipase B was successfully immobilized on magnetite (Fe3O4)
      nanoparticles functionalized with chitosan and glutaraldehyde. The obtained
      magnetic catalyst was characterized and its performance was evaluated in solvent
      free synthesis of ethyl oleate at room temperature. The performance of this
      biocatalyst was compared with the commercial Novozym 435, as a tool to estimate
      the efficiency of immobilization. It was found that using 33 mg of the
      biocatalyst it was possible to reach almost the same activity that was obtained
      using 12 mg of Novozym 435. Furthermore, this new biocatalyst presents the
      advantages of not being degraded by short alcohols, being easily recovered from
      the reaction media by magnetic decantation, and low fabrication cost. The
      possibility of reutilization was also studied, keeping a significant activity up
      to eight cycles. A special sampling protocol was also developed for the
      multiphasic reaction system, to assure accurate results. This novel biocatalyst
      is an interesting alternative for potential industrial applications, considering
      the above-mentioned advantages. 

PMID- 23860560
TI  - Intrasurgical dynamics of macular hole surgery: an assessment of surgery-induced
      ultrastructural alterations with intraoperative optical coherence tomography.
AB  - PURPOSE: To evaluate the intrasurgical retinal architectural and macular hole
      (MH) geometric alterations that occur during surgical MH repair using
      intraoperative optical coherence tomography. METHODS: A retrospective,
      multisurgeon, single-center, consecutive case series of 21 eyes undergoing
      surgical repair for MH with concurrent intraoperative optical coherence
      tomography using a custom microscope-mounted optical coherence tomography system
      was performed. All patients underwent surgical repair with pars plana vitrectomy,
      membrane peel, and gas tamponade. A novel three-dimensional segmentation
      algorithm was used for volumetric analysis of intrasurgical changes of MH
      geometry after surgical repair. Intraoperative optical coherence tomographic
      characteristics analyzed included MH volume, minimum diameter, base area, and
      hole height. Outer retinal architecture changes were analyzed both quantitatively
      and qualitatively. RESULTS: All 21 eyes were successfully imaged with
      intraoperative optical coherence tomography. Nineteen of 21 eyes had images of
      sufficient signal strength to allow for quantitative analysis. Significant
      changes were noted in MH geometry after internal limiting membrane peeling
      including increased MH volume, increased base area, and decreased top area (all P
      < 0.03). Additionally, increased subretinal hyporeflectance was noted by
      expansion of the height between the inner segment/outer segment and retinal
      pigment epithelium bands (P = 0.008). Peeling methods and surgeon experience did
      not correlate with the magnitude of architectural alterations. Macular hole
      algorithm measurements and alterations were associated with visual outcome and MH
      closure. CONCLUSION: Significant alterations occur in MH geometry and outer
      retinal structure after internal limiting membrane peeling. These changes are
      subclinical and unable to be appreciated with en face surgical microscope viewing
      and require intraoperative optical coherence tomography for visualization.
      Preliminary analysis of these measurements identified an association with visual
      outcome and successful MH closure. The functional significance of these changes
      deserves further study.

PMID- 23860561
TI  - Spectral domain optical coherence tomography findings in patients with acute
      syphilitic posterior placoid chorioretinopathy.
AB  - PURPOSE: To describe the appearance of acute syphilitic posterior placoid
      chorioretinitis, a rare ocular manifestation of syphilis, on spectral domain
      optical coherence tomography (SD OCT) both before and after treatment. METHODS:
      Ophthalmic examination and imaging studies of 30 eyes of 19 confirmed cases were
      analyzed both at the time of presentation and at each follow-up visit. Patients
      with SD OCT and fluorescein angiography at the time of presentation, and at least
      three documented follow-up visits after initiation of therapy, were included in
      the study. Standard treatment of neurosyphilis was given to each patient,
      including 4 million units of penicillin G administered intravenously every 4
      hours for 14 days. RESULTS: Fundus examination and imaging studies were
      consistent with previous reports and confirmed the diagnosis of acute syphilitic
      posterior placoid chorioretinitis. In 13 eyes (43.3%), baseline SD OCT scans were
      performed within 1 to 2 days of presentation and revealed a small amount of
      subretinal fluid, disruption of the inner segment/outer segment junction, and
      hyperreflective thickening of the retinal pigment epithelium (RPE). All 30 eyes
      were again scanned between Days 7 and 9 after presentation and revealed loss of
      the inner segment/outer segment and OS/RPE bands, and irregular hyperreflectivity
      of the RPE with prominent nodular elevations but without subretinal fluid. Early
      disruption of the external limiting membrane and punctate choroidal
      hyperreflectivity were seen in 1 of the 30 eyes (3.3%) and 14 of the 30 eyes
      (46.6%), respectively. Vision improved and the outer retinal abnormalities
      normalized in 28 of the 30 eyes (93.3%) after the treatment of neurosyphilis. The
      external limiting membrane, inner segment/outer segment band, and/or linear outer
      segment/RPE junction remained substantially abnormal despite treatment in 2 eyes
      left with 20/200 vision. CONCLUSION: Patients with acute syphilitic posterior
      placoid chorioretinitis show characteristic outer retinal abnormalities on SD OCT
      imaging, including disruption of the inner segment/outer segment band, nodular
      thickening of the RPE with loss of the linear outer segment/RPE junction, and, in
      some cases, loss of the external limiting membrane, accumulation of subretinal
      fluid, and punctate hyperreflectivity in the choroid. Vision improved and these
      abnormalities reversed after treatment of neurosyphilis in most of the patients.
      Persistently, poor vision despite treatment was associated with long-term loss or
      disruption of outer retinal anatomy on SD OCT.

PMID- 23860564
TI  - Identification, characterization, and application of a virulence factor (EfEstA)
      from Enterococcus faecalis.
AB  - Although virulence factors from pathogenic bacteria have been proposed as
      promising industrial enzymes, characterization and application of these enzymes
      have been still unexplored. The objective of this study was to identify and
      characterize virulence factors from pathogenic bacteria for industrial
      applications. Here, a virulence factor (EfEstA) from Enterococcus faecalis was
      identified and characterized using SDS-PAGE, enzyme assays, and molecular
      modeling. In addition, it has been shown that cross-linked enzyme aggregates
      (CLEAs) of EfEstA exhibited improved stabilities and high recycling activities
      compared to free EfEstA. These characteristics of EfEstA shed light on the design
      of new lipase-based systems for industrial applications. 

PMID- 23860563
TI  - Measuring treatment coverage for neglected tropical disease control programs:
      analysis of a survey design.
AB  - Monitoring of treatment coverage following mass drug administration is essential
      to ensure program success. Coverage results reported by drug administrators are
      often validated by using population surveys. This study evaluates the design of a
      multistage cluster sample survey conducted in 2007-2008 and implemented at the
      district level to assess drug coverage in the 4 African countries of Burkina
      Faso, Ghana, Niger, and Uganda. Estimates of precision of coverage were
      calculated, and factors contributing to the observed variance were analyzed.
      Precision of +/-5 percentage points was obtained in 39% (n = 12) of cases, and
      precision of +/-10 percentage points was obtained in 77% (n = 24) of cases. The
      factor having the largest impact on the actual precision obtained in these
      surveys was the high level of clustering, the impact of which is incorporated in
      the design effect. Key recommendations are made for the design and analysis of
      future surveys; guidelines are presented for thinking through the number of
      clusters that should be selected and how a cluster should be designed.

PMID- 23860565
TI  - The timing of tremor: a biological clock in essential tremor?

PMID- 23860566
TI  - Management of the elderly patients with inflammatory bowel disease: practical
      considerations.
AB  - The aging U.S. population will approach 20% of the total population by 2030. The
      number of older patients with inflammatory bowel disease is anticipated to
      increase accordingly bringing the burden of multiple comorbidities, polypharmacy
      with drug interactions, the aging immune system, and extended social and
      financial issues to overall management of an already challenging management of
      these patients. Each of these concerns is measured by the metric of
      distinguishing the "fit versus frail" elderly and will be discussed in this
      review with an emphasis on a practical guide to therapy.

PMID- 23860567
TI  - Infliximab reduces hospitalizations and surgery interventions in patients with
      inflammatory bowel disease: a systematic review and meta-analysis.
AB  - BACKGROUND: We systematically reviewed infliximab benefit in reducing
      hospitalizations and/or major surgery rates in patients with inflammatory bowel
      disease (IBD). METHODS: A literature search to May 2012 was performed to identify
      all studies (experimental and observational) evaluating patients with IBD treated
      with infliximab and providing data on hospitalizations and/or major surgery
      rates. Three reviewers independently performed studies' selection, quality
      assessment, and data extraction. Analyses were carried according to study design
      (randomized clinical trials [RCTs] and observational studies) and IBD type
      (Crohn's disease [CD] and ulcerative colitis [UC]). Random-effects meta-analysis
      was used to derive pooled and 95% confidence intervals (CIs) estimates of odds
      ratios (OR). Heterogeneity was assessed with I test. RESULTS: Twenty-seven
      eligible studies were included (9 RCTs and 18 observational studies). Infliximab
      reduced hospitalization risk, both in pooled RCTs (OR, 0.51; 95% CI 0.40-0.65; I
      = 0%) and results of observational studies (OR, 0.29, 95% CI, 0.19-0.43; I =
      87%), without differences between CD and UC. Infliximab reduced surgery risk in
      pooled RCTs results, both in CD (OR, 0.31; 95% CI, 0.15-0.64; I = 0%) and UC (OR,
      0.57; 95% CI, 0.37-0.88; I = 0%). Pooled estimate from observational studies
      favored infliximab for patients with CD (OR, 0.32; 95% CI, 0.21-0.49; I = 77%),
      but not for patients with UC. CONCLUSIONS: The best evidence available points
      toward a reduction of the risk of hospitalization and major surgery requirement
      in patients with IBD treated with infliximab. This impact is clinically and
      economically relevant because hospitalization and surgery are considered to be
      markers of disease severity and significantly contribute to the total direct
      costs associated with IBD.

PMID- 23860568
TI  - Fluoxetine treatment promotes functional recovery in a rat model of cervical
      spinal cord injury.
AB  - Spinal cord injury (SCI) is a severe condition leading to enduring motor
      deficits. When lesions are incomplete, promoting spinal cord plasticity might be
      a useful strategy to elicit functional recovery. Here we investigated whether
      long-term fluoxetine administration in the drinking water, a treatment recently
      demonstrated to optimize brain plasticity in several pathological conditions,
      promotes motor recovery in rats that received a C4 dorsal funiculus crush. We
      show that fluoxetine administration markedly improved motor functions compared to
      controls in several behavioral paradigms. The improved functional effects
      correlated positively with significant sprouting of intact corticospinal fibers
      and a modulation of the excitation/inhibition balance. Our results suggest a
      potential application of fluoxetine treatment as a non invasive therapeutic
      strategy for SCI-associated neuropathologies. 

PMID- 23860569
TI  - Modeling the mechanism of glycosylation reactions between ethanol, 1,2-ethanediol
      and methoxymethanol.
AB  - The mechanism of the S(N)2 model glycosylation reaction between ethanol, 1,2
      ethanediol and methoxymethanol has been studied theoretically at the B3LYP/6
      311+G(d,p) computational level. Three different types of reactions have been
      explored: (i) the exchange of hydroxyl groups between these model systems; (ii)
      the basic catalysis reactions by combination of the substrates as glycosyl donors
      (neutral species) and acceptors (enolate species); and (iii) the effect on the
      reaction profile of an explicit H2O molecule in the reactions considered in (ii).
      The reaction force, the electronic chemical potential and the reaction electronic
      flux have been characterized for the reaction path in each case. Energy
      calculations show that methoxymethanol is the worst glycosyl donor model among
      the ones studied here, while 1,2-ethanediol is the best, having the lowest
      activation barrier of 74.7 kJ mol(-1) for the reaction between this one and the
      ethanolate as the glycosyl acceptor model. In general, the presence of direct
      interactions between the atoms involved in the penta-coordinated TS increases the
      activation energies of the processes.

PMID- 23860571
TI  - Brown fat in a protoendothermic mammal fuels eutherian evolution.
AB  - Endothermy has facilitated mammalian species radiation, but the sequence of
      events leading to sustained thermogenesis is debated in multiple evolutionary
      models. Here we study the Lesser hedgehog tenrec (Echinops telfairi), a
      phylogenetically ancient, 'protoendothermic' eutherian mammal, in which
      constantly high body temperatures are reported only during reproduction. Evidence
      for nonshivering thermogenesis is found in vivo during periodic ectothermic
      endothermic transitions. Anatomical studies reveal large brown fat-like
      structures in the proximity of the reproductive organs, suggesting physiological
      significance for parental care. Biochemical analysis demonstrates high
      mitochondrial proton leak catalysed by an uncoupling protein 1 ortholog.
      Strikingly, bioenergetic profiling of tenrec uncoupling protein 1 reveals similar
      thermogenic potency as modern mouse uncoupling protein 1, despite the large
      phylogenetic distance. The discovery of functional brown adipose tissue in this
      'protoendothermic' mammal links nonshivering thermogenesis directly to the roots
      of eutherian evolution, suggesting physiological importance prior to sustained
      body temperatures and migration to the cold. 

PMID- 23860572
TI  - Rasburicase causing severe oxidative hemolysis and methemoglobinemia in a patient
      with previously unrecognized glucose-6-phosphate dehydrogenase deficiency.
AB  - Rasburicase is frequently used in tumor lysis syndrome (TLS). Although it is very
      well tolerated, it can cause severe oxidative hemolytic anemia and
      methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD)
      deficiency. We report another case of rasburicase-induced methemoglobinemia in a
      patient with previously unrecognized G6PD deficiency and review the cases of
      methemoglobinemia and oxidative hemolysis reported in the literature to date.
      Patients from ethnicities in which G6PD deficiency is prevalent at high risk of
      TLS should be screened for G6PD deficiency prior to administration of rasburicase
      where practical. Asymptomatic decrease in oxygen saturation by oximetry and
      cyanosis are signs of methemoglobinemia; patients recover with conservative
      measures including supplemental oxygen and packed red cell transfusion. 

PMID- 23860573
TI  - Na2Ti6O13: a potential anode for grid-storage sodium-ion batteries.
AB  - The ultra-fast (30C or 2 min) rate capability and impressive long cycle life
      (>5000 cycles) of Na2Ti6O13 are reported. A stable 2.5 V sodium-ion battery full
      cell is demonstrated. In addition, the sodium storage mechanism and thermal
      stability of Na2Ti6O13 are discussed.

PMID- 23852273
TI  - Twitter as a sentinel in emergency situations: lessons from the Boston marathon
      explosions.
AB  - Immediately following the Boston Marathon attacks, individuals near the scene
      posted a deluge of data to social media sites. Previous work has shown that these
      data can be leveraged to provide rapid insight during natural disasters, disease
      outbreaks and ongoing conflicts that can assist in the public health and medical
      response. Here, we examine and discuss the social media messages posted
      immediately after and around the Boston Marathon bombings, and find that specific
      keywords appear frequently prior to official public safety and news media
      reports. Individuals immediately adjacent to the explosions posted messages
      within minutes via Twitter which identify the location and specifics of events,
      demonstrating a role for social media in the early recognition and
      characterization of emergency events. *Christopher Cassa and Rumi Chunara
      contributed equally to this work. 

PMID- 23860575
TI  - Exposure and effects of perfluoroalkyl substances in tree swallows nesting in
      Minnesota and Wisconsin, USA.
AB  - The exposure and effects of perfluoroalkyl substances (PFASs) were studied at
      eight locations in Minnesota and Wisconsin between 2007 and 2011 using tree
      swallows (Tachycineta bicolor). Concentrations of PFASs were quantified as were
      reproductive success end points. The sample egg method was used wherein an egg
      sample is collected, and the hatching success of the remaining eggs in the nest
      is assessed. The association between PFAS exposure and reproductive success was
      assessed by site comparisons, logistic regression analysis, and multistate
      modeling, a technique not previously used in this context. There was a negative
      association between concentrations of perfluorooctane sulfonate (PFOS) in eggs
      and hatching success. The concentration at which effects became evident (150-200
      ng/g wet weight) was far lower than effect levels found in laboratory feeding
      trials or egg-injection studies of other avian species. This discrepancy was
      likely because behavioral effects and other extrinsic factors are not accounted
      for in these laboratory studies and the possibility that tree swallows are
      unusually sensitive to PFASs. The results from multistate modeling and simple
      logistic regression analyses were nearly identical. Multistate modeling provides
      a better method to examine possible effects of additional covariates and
      assessment of models using Akaike information criteria analyses. There was a
      credible association between PFOS concentrations in plasma and eggs, so
      extrapolation between these two commonly sampled tissues can be performed. 

PMID- 23860576
TI  - Selective sensing of saccharides using simple boronic acids and their aggregates.
AB  - The reversible boronic acid-diol interaction empowers boronic acid receptors'
      saccharide binding capacities, rendering them a class of lectin mimetic, termed
      "boronlectins". Boronic acids follow lectin functions not just in being able to
      bind saccharides, but in multivalent saccharide binding that enhances both
      affinity and selectivity. For almost a decade, efforts have been made to achieve
      and improve selectivity for given saccharide targets, most notably glucose, by
      using properly positioned boronic acids, offering multivalent interactions.
      Incorporation of several boronic acid groups into a covalent framework or non
      covalent assembly of boronic acid are two general methods used to create such
      smart sensors, of which the latter resembles lectin oligomerisation that affords
      multivalent saccharide-binding architectures. In this review, we discuss
      supramolecular selective sensing of saccharides by using simple boronic acids in
      their aggregate forms, after a brief survey of the general aspects of boronic
      acid-based saccharide sensing. 

PMID- 23860578
TI  - [Shoulder].

PMID- 23860577
TI  - Characterization of the Zhikong scallop (Chlamys farreri) mantle transcriptome
      and identification of biomineralization-related genes.
AB  - Chlamys farreri is a significant species in aquaculture and fishery in East Asia.
      A deep understanding of its shell formation by studying the transcriptome of the
      mantle, a key organ in shell formation, could provide important guidance for its
      culture. Thus, we sequenced and analyzed the mantle transcriptome of C. farreri.
      The 77,975 unigenes were generated after Illumina sequencing and de novo
      assembly. The unigenes were annotated using authoritative databases (non
      redundant (NR), COG, Gene Ontology (GO), and KEGG) to obtain functional
      information. BLASTX alignment was performed between unigenes and reported
      proteins related to biomineralization. The results identified 53 homologous genes
      representing 17 matrix proteins, most of which are involved in calcite formation,
      and 171 homologies with 26 proteins related to general processes of
      biomineralization. The discovery and unusually high expression of MSP-1 suggested
      its importance in scallops. Homologous unigenes with aragonite-formation-related
      matrix proteins were much fewer compared with those related to calcite formation.
      The results implied that, in C. farreri, the number and proportion of matrix
      proteins related to aragonite formation is much lower than those related to
      calcite formation, which was consistent with the proportions of aragonite and
      calcite in C. farreri shells. Thus, the formation of different polymorphs of
      calcium carbonate (calcite and aragonite) in molluskan shells is regulated by
      different groups of proteins. Moreover, 17 candidate unigenes, which are probably
      involved in biomineralization, were predicted by screening for gene products with
      secreted domains and tandem-arranged repeat units. Our results contribute to the
      understanding of biomineralization processes and the evolution of shell
      formation. 

PMID- 23860579
TI  - [Non-unions. From diagnosis to healing].
AB  - Non-unions are a relevant medical and socio-economic problem. Hyper-, oligo- and
      atrophic non-unions as well as septic and aseptic non-unions are differentiated.
      Correct classification is essential for the selected therapy. The "diamond
      concept" describes five pillars, on which bone healing is based and that have to
      be considered in the treatment of non-unions: osteogenic cells (mesenchymal stem
      cells), osteoinduction (growth factors), osteoconduction (scaffolds), mechanical
      stability, and vascularization. Factors that predispose to non-union also
      influence fracture healing. The gold standard of therapy are still resection of
      the non-union, decortication and autologous bone grafting. No advantage could be
      proven for any of the numerous procedures in monotherapy. But the combination of
      various procedures - polytherapy - seems to be promising. The aim is to optimize
      these concepts. 

PMID- 23860580
TI  - What's new in shock? August 2013.

PMID- 23860581
TI  - Perturbed mononuclear phagocyte system in severely burned and septic patients.
AB  - Burn is one of the most common and devastating forms of trauma. Major burn injury
      disturbs the immune system, resulting in marked alterations in bone marrow
      hematopoiesis and a progressive suppression of the immune response, which are
      thought to contribute to increased susceptibility to secondary infections and the
      development of sepsis. Immunosuppression in patients with severe burn and sepsis
      leads to high morbidity and mortality in these patients. mononuclear phagocytes
      system (MPS) is a critical component of the innate immune response and plays key
      roles in burn immunity. These phagocytes are the first cellular responders to
      severe burn injury after acute disruption of the skin barrier. They are not only
      able to internalize and digest bacteria and dead cells and scavenge toxic
      compounds produced by metabolism, but also able to initiate an adaptive immune
      response. Severe burn and sepsis profoundly inhibit the functions of dendritic
      cells, monocytes, and macrophages. Adoptive transfer of MPS or stem cells to
      patients with severe burn and sepsis that aim to restore MPS function is
      promising. A better understanding of the roles played by MPS in the
      pathophysiology of severe burn and sepsis will guarantee a more rational and
      effective immunotherapy of patients with severe burn and sepsis. 

PMID- 23860582
TI  - Monocyte human leukocyte antigen-DR expression-a tool to distinguish intestinal
      bacterial infections from inflammatory bowel disease?
AB  - BACKGROUND: We sought to determine the quantitative expression of human leukocyte
      antigen-DR (HLA-DR) on monocytes in patients with acute intestinal bacterial
      infections and inflammatory bowel disease (IBD). METHODS: The quantitative
      expression of HLA-DR on monocytes was determined by fluorescence-activated cell
      sorting analysis in patients with IBD, patients with acute intestinal bacterial
      infections (bact.), and healthy subjects (contr.). RESULTS: The quantitative
      expression of HLA-DR in patients with bact. (n = 20; 90,000 molecules per
      monocyte; confidence interval [CI], 79,000-102,000) was significantly higher than
      that in patients with ulcerative colitis (n = 40, 30,000; CI, 30,000-38,000; P <
      0.0001), Crohn disease (n = 80, 31,000; CI, 32,000-39,000; P < 0.0001), or in
      contr. (n = 28, 39,000; CI, 36,000-46,000; P < 0.0001). In patients with
      ulcerative colitis and Crohn disease, HLA-DR expression was significantly
      decreased, as compared with contr. (P < 0.05 and P < 0.01, respectively). With a
      cutoff point of 50,000, HLA-DR showed a sensitivity of 95% and a specificity of
      92% in discriminating between bact. and active IBD. CONCLUSION: The quantitative
      measurement of HLA-DR expression could serve as a valuable tool to discriminate
      between bact. and active IBD.

PMID- 23860583
TI  - Vagus nerve stimulation attenuates intestinal epithelial tight junctions
      disruption in endotoxemic mice through alpha7 nicotinic acetylcholine receptors.
AB  - We tested the effect of vagus nerve stimulation in endotoxin-induced intestinal
      tight junction injury in mice challenged with lipopolysaccharide (LPS) and
      examined the role of alpha7 nicotinic acetylcholine receptors (alpha7nAchR) in
      this process. Endotoxemia was induced by intraperitoneal injection of LPS (10
      mg/kg) in male Balb/c mice. Samples were collected 12 h after LPS treatment.
      Endotoxemia was associated with intestinal barrier dysfunction, as evidenced by
      increased amount of fluorescein isothiocyanate-dextran in circulation. Western
      blot and immunofluorescence was performed, and the results demonstrated decreased
      expression of occludin and zonula occludens 1 along intestinal epithelium in
      endotoxemic mice. The ultrastructure of tight junction was disrupted as shown by
      transmission electron microscopy, which was associated with increased intestinal
      permeability. Stimulation of the right cervical vagus nerve ameliorated the
      damage of tight junction ultrastructure, which was consistent with decreased
      permeability to fluorescein isothiocyanate-dextran, and also reversed the
      decreased expression of tight junction proteins occludin and zonula occludens 1.
      Vagus nerve stimulation inhibited the upregulated activity of myosin light chain
      kinase and nuclear factor kappaB. In contrast, alpha-bungarotoxin (a specific
      alpha7nAchR antagonist, 0.1 MUg/mouse) administered before vagus nerve
      stimulation significantly abolished these protective effects of vagus nerve
      stimulation. Our results for the first time confirmed that vagus nerve
      stimulation attenuated the disruption of tight junction in intestinal epithelium
      in endotoxemic mice, which was mediated through suppressing translocation of
      nuclear factor kappaB p65, downregulating myosin light chain kinase, and the
      alpha7nAchR may play an important role in this process. 

PMID- 23860584
TI  - Tranexamic acid and trauma: current status and knowledge gaps with recommended
      research priorities.

PMID- 23860585
TI  - An observational study of adults with Down syndrome eating independently.
AB  - This study examined the oral feeding in a group of adults with Down syndrome.
      None of the 23 participants in the study had reported oral feeding difficulties,
      and all independently ate a full oral diet (food and liquids). Observations were
      made during the consumption of one meal and one drink. The eating and drinking
      behaviours observed included eating rate and ability to keep food in the mouth,
      and these were considered in conjunction with oral and pharyngeal phase skills
      and difficulties. Coughing, an overt sign of possible aspiration with its
      attendant risk of upper respiratory tract infection, was seen in 56.5 % of
      participants. In addition, several of the observed oral feeding behaviours of
      this group of individuals may be socially unacceptable and therefore likely to
      compromise quality of life. A number of behaviours with implications for both
      health and quality of life may be amenable to simple behaviour modification or to
      changes to the environment. Further study into the causes of these oral feeding
      difficulties, their implications for social integration, and their potential
      remediation is required. 

PMID- 23860586
TI  - Overexpression of suppressor of cytokine signaling 3 in the arcuate nucleus of
      juvenile Phodopus sungorus alters seasonal body weight changes.
AB  - The profound seasonal cycle in body weight exhibited by the Djungarian hamster
      (Phodopus sungorus) is associated with the development of hypothalamic leptin
      resistance during long day photoperiod (LD, 16:8 h light dark cycle), when body
      weight is elevated relative to short day photoperiod (SD, 8:16 h light dark
      cycle). We previously have shown that this seasonal change in physiology is
      associated with higher levels of mRNA for the potent inhibitor of leptin
      signaling, suppressor of cytokine signaling-3 (SOCS3), in the arcuate nucleus
      (ARC) of LD hamsters relative to hamsters in SD. The alteration in SOCS3 gene
      expression preceded the body weight change suggesting that SOCS3 might be the
      molecular switch of seasonal body weight changes. To functionally characterize
      the role of SOCS3 in seasonal body weight regulation, we injected SOCS3
      expressing recombinant adeno-associated virus type-2 (rAAV2-SOCS3) constructs
      into the ARC of leptin sensitive SD hamsters immediately after weaning. Hamsters
      that received rAAV2 expressing enhanced green fluorescent protein (rAAV2-EGFP)
      served as controls. ARC-directed SOCS3 overexpression led to a significant
      increase in body weight over a period of 12 weeks without fully restoring the LD
      phenotype. This increase was partially due to elevated brown and white adipose
      tissue mass. Gene expression of pro-opiomelanocortin was increased while thyroid
      hormone converting enzyme DIO3 mRNA levels were reduced in SD hamsters with SOCS3
      overexpression. In conclusion, our data suggest that ARC-directed SOCS3
      overexpression partially overcomes the profound seasonal body weight cycle
      exhibited by the hamster which is associated with altered pro-opiomelanocortin
      and DIO3 gene expression. 

PMID- 23860587
TI  - Oxidative dehydrogenation of a new tetra-amine N4-donor macrocycle tunes the
      nickel(II) spin state from high spin to low spin.
AB  - The nickel(II) spin state in a series of N4-donor macrocycles differing in the
      number of imine bonds is tuned from low spin (2 imines) to low or high spin (1
      imine; non- or coordinating co-ligand) to high spin (no imines).

PMID- 23860589
TI  - Convenient synthesis of heterobifunctional poly(ethylene glycol) suitable for the
      functionalization of iron oxide nanoparticles for biomedical applications.
AB  - A straightforward route is proposed for the multi-gram scale synthesis of
      heterobifunctional poly(ethylene glycol) (PEG) oligomers containing combination
      of triethyloxysilane extremity for surface modification of metal oxides and amino
      or azido active end groups for further functionalization. The suitability of
      these PEG derivatives to be conjugated to nanomaterials was shown by pegylation
      of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs), followed
      by functionalization with small peptide ligands for biomedical applications. 

PMID- 23860588
TI  - Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the
      published literature.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is relatively rare, yet the
      economic and social burden is substantial. Having accurate incidence and
      prevalence estimates would facilitate efficient allocation of healthcare
      resources. OBJECTIVE: To provide a comprehensive and critical review of the
      epidemiological literature on ALS. METHODS: MEDLINE and EMBASE (1995-2011)
      databases of population-based studies on ALS incidence and prevalence reporting
      quantitative data were analyzed. Data extracted included study location and time,
      design and data sources, case ascertainment methods and incidence and/or
      prevalence rates. Medians and interquartile ranges (IQRs) were calculated, and
      ALS case estimates were derived using 2010 population estimates. RESULTS: In all,
      37 articles met the inclusion criteria. In Europe, the median incidence rate
      (/100,000 population) was 2.08 (IQR 1.47-2.43), corresponding to an estimated
      15,355 (10,852-17,938) cases. Median prevalence (/100,000 population) was 5.40
      (IQR 4.06-7.89), or 39,863 (29,971-58,244) prevalent cases. CONCLUSIONS:
      Disparity in rates among ALS incidence and prevalence studies may be due to
      differences in study design or true variations in population demographics such as
      age and geography, including environmental factors and genetic predisposition.
      Additional large-scale studies that use standardized case ascertainment methods
      are needed to more accurately assess the true global burden of ALS.

PMID- 23860590
TI  - Synthesis and cytotoxic activity evaluation of 2,3-thiazolidin-4-one derivatives
      on human breast cancer cell lines.
AB  - It is well known that resveratrol (RSV) displayed cancer-preventing and
      anticancer properties but its clinical application is limited because of a low
      bioavailability and a rapid clearance from the circulation. Aim of this work was
      to synthesize pharmacologically active resveratrol analogs with an enhanced
      structural rigidity and bioavailability. In particular, we have synthesized a
      library of 2,3-thiazolidin-4-one derivatives in which a thiazolidinone nucleus
      connects two aromatic rings. Some of these compounds showed strong inhibitory
      effects on breast cancer cell growth. Our results indicate that some of
      thiazolidin-based resveratrol derivatives may become a new potent alternative
      tool for the treatment of human breast cancer. 

PMID- 23860591
TI  - Selected furanochalcones as inhibitors of monoamine oxidase.
AB  - The validity of the chalcone scaffold for the design of inhibitors of monoamine
      oxidase has previously been illustrated. In a systematic attempt to investigate
      the effect of heterocyclic substitution on the monoamine oxidase inhibitory
      properties of this versatile scaffold, a series of furanochalcones were
      synthesized. The results demonstrate that these furan substituted
      phenylpropenones exhibited moderate to good inhibitory activities towards MAO-B,
      but showed weak or no inhibition of the MAO-A enzyme. The most active compound,
      2E-3-(5-chlorofuran-2-yl)-1-(3-chlorophenyl)prop-2-en-1-one, exhibited an IC50
      value of 0.174 MUM for the inhibition of MAO-B and 28.6 MUM for the inhibition of
      MAO-A. Interestingly, contrary to data previously reported for chalcones, these
      furan substituted derivatives acted as reversible inhibitors, while kinetic
      analysis revealed a competitive mode of binding.

PMID- 23860592
TI  - Design, synthesis and biological evaluation of novel triaryl (Z)-olefins as
      tamoxifen analogues.
AB  - Tamoxifen (TAM) is used for the treatment and prevention of estrogen receptor
      positive breast cancer. However, the limited activity, toxicity and the
      development of resistance raised the current need for new potent nontoxic
      antiestrogen. Six novel TAM analogues 5a-f were synthesized using McMurry
      olefination reaction. Replacement of the dimethylamino group in TAM by
      piperidino, piperazino or N-methyl piperazino, substituting the phenyl ring with
      florine atom at p-position and changing the ethyl group by methyl, afforded
      compounds showing comparable activity to TAM (1). Compounds 5c and 5e showed
      significant increase in antiproliferative activity in two breast cancer cell
      lines (MCF-7 and MDA-MB-231) compared to tamoxifen, while other compounds showed
      similar activity. The increased anticancer activity of compounds 5c and 5e was
      attributed to their ability to induce ER-independent cell death. 

PMID- 23860593
TI  - Novel beta-dicarbonyl derivatives as inhibitors of aminopeptidase N (APN).
AB  - Most zinc metalloproteases are over-expressed in tumor cells and play a critical
      role in the genesis, development, and metastasis of tumors. Novel zinc binding
      groups (ZBGs) represent a novel strategy to obtain optimal potency and
      selectivity for zinc metalloproteases inhibitors. Here we described the design,
      synthesis, and biological studies of novel beta-dicarbonyl derivatives as
      aminopeptidase N (APN/CD13) inhibitors. The results demonstrated that some
      compounds exhibited moderate to good inhibitory activities against APN with
      compound 5c being the most potent, suggesting that 5c could serve as new lead for
      the future APN inhibitor development. The results further confirm our design
      rationale of beta-dicarbonyl moiety as a new ZBG, which may provide a new
      direction for the design and discovery of zinc metalloproteases inhibitors as new
      anti-tumor agents. 

PMID- 23860594
TI  - Forecasting large aftershocks within one day after the main shock.
AB  - Forecasting the aftershock probability has been performed by the authorities to
      mitigate hazards in the disaster area after a main shock. However, despite the
      fact that most of large aftershocks occur within a day from the main shock, the
      operational forecasting has been very difficult during this time-period due to
      incomplete recording of early aftershocks. Here we propose a real-time method for
      efficiently forecasting the occurrence rates of potential aftershocks using
      systematically incomplete observations that are available in a few hours after
      the main shocks. We demonstrate the method's utility by retrospective early
      forecasting of the aftershock activity of the 2011 Tohoku-Oki Earthquake of M9.0
      in Japan. Furthermore, we compare the results by the real-time data with the
      compiled preliminary data to examine robustness of the present method for the
      aftershocks of a recent inland earthquake in Japan. 

PMID- 23860595
TI  - New genetic discoveries and primary immune deficiencies.
AB  - The field of immunology has undergone recent discoveries of genetic causes for
      many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has
      led to increased understanding behind the pathophysiology of these diseases.
      Since these diseases are rare, the patients are frequently misdiagnosed early in
      the presentation of their illnesses. The identification of new genes has
      increased our opportunities for recognizing and making the diagnosis in patients
      with PIDD before they succumb to infections that may result secondary to their
      PIDD. Some mutations lead to a variety of presentations of severe combined
      immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead
      to SCID phenotypes have been identified in recent years. Other mutations
      associated with some genetic syndromes have associated immunodeficiency and are
      important for making the diagnosis of primary immunodeficiency in patients with
      some syndromes, who may otherwise be missed within the larger context of their
      syndromes. A variety of mutations also lead to increased susceptibility to
      infections due to particular organisms. These patterns of infections due to
      specific organisms are important keys in properly identifying the part of the
      immune system which is affected in these patients. This review will discuss
      recent genetic discoveries that enhance our understanding of these complex
      diseases. 

PMID- 23860596
TI  - A nanocarrier based on a genetically engineered protein cage to deliver
      doxorubicin to human hepatocellular carcinoma cells.
AB  - Herein, we report the preparation of genetically engineered protein cages
      (HspG41C-SP94), taken up selectively by human hepatocellular carcinoma (HCC)
      cells. An engineered protein cage-doxorubicin (DOX) conjugate was as cytotoxic as
      free DOX against HCC cells but much less cytotoxic against normal hepatocytes.

PMID- 23860597
TI  - Effects of diethylphthalate and di-(2-ethyl)hexylphthalate on the physiology and
      ultrastructure of cucumber seedlings.
AB  - Phthalic acid esters (PAEs) are one kind of persistent organic pollutants. This
      study was conducted to investigate the effects of diethylphthalate (DEP) and di(2
      ethyl)hexylphthalate (DEHP) with different concentrations (0, 30, 50, 100, and
      200 mg L(-1)) on early seedling growth of Cucumis sativus L. Physiological,
      biochemical, and ultrastructure of seedling leaves were examined for 7-day
      exposure. The three antioxidant enzymes' activities was stimulated at low-DEP
      treatments and decreased under higher levels (>200 mg L(-1)) compared to the
      controls. Furthermore, MDA and H2O2 gradually enhanced with the elevation of DEP
      and DEHP concentration. Significant impact on the chloroplast and mitochondrion
      was visible, possibly as a consequence of free radical generation. DEP induced
      bigger and more starch grains in chloroplasts than DEHP. This study concluded
      that the effects of DEP and DEHP on cucumber seedlings represented the adverse
      impacts of DEP and DEHP on the ecosystem and agricultural production. The
      environmental harm caused by DEP was severer than DEHP. 

PMID- 23860598
TI  - Evaluation of growth and biochemical indicators of Salvinia natans exposed to
      zinc oxide nanoparticles and zinc accumulation in plants.
AB  - The adverse effects of zinc oxide nanoparticles (ZnO NPs) with an average
      diameter of 25 nm on the aquatic plant Salvinia natans (L.) All. were determined.
      Growth, superoxide dismutase (SOD) activity, catalase (CAT) activity, peroxidase
      activity, and chlorophyll content of the plants were measured after 7 days of
      exposure to different concentrations of ZnO NPs (1 to 50 mg L(-1)). The particle
      distribution in the culture medium (without plants) during the first 24 h was
      determined using a Nanotrac 250 particle analyzer. We also investigated the zinc
      accumulation in leaves and roots of the plant after 7 days of exposure. Exposure
      to 50 mg L(-1) ZnO NPs significantly increased SOD and CAT activities (P < 0.05)
      and significantly depressed photosynthetic pigments (P < 0.05). However, plant
      growth was not significantly affected (P > 0.05). NPs completely precipitated at
      the bottom of the container at 8 h except for the portions of dissolution and
      aggregation on the roots. ZnO NPs at a concentration of 50 mg L(-1) can adversely
      affect S. natans, and their stress is affected by their aggregation and
      dissolution. 

PMID- 23860599
TI  - Mass-encoded, synthetic biomarkers and multiplexed urinary monitoring: new
      frontiers in disease monitoring.

PMID- 23860600
TI  - Focal uncaging of GABA reveals a temporally defined role for GABAergic inhibition
      during appetitive associative olfactory conditioning in honeybees.
AB  - Throughout the animal kingdom, the inhibitory neurotransmitter gamma-aminobutyric
      acid (GABA) is a key modulator of physiological processes including learning.
      With respect to associative learning, the exact time in which GABA interferes
      with the molecular events of learning has not yet been clearly defined. To
      address this issue, we used two different approaches to activate GABA receptors
      during appetitive olfactory conditioning in the honeybee. Injection of GABA-A
      receptor agonist muscimol 20 min before but not 20 min after associative
      conditioning affects memory performance. These memory deficits were attenuated by
      additional training sessions. Muscimol has no effect on sensory perception, odor
      generalization, and nonassociative learning, indicating a specific role of GABA
      during associative conditioning. We used photolytic uncaging of GABA to identify
      the GABA-sensitive time window during the short pairing of the conditioned
      stimulus (CS) and the unconditioned stimulus (US) that lasts only seconds. Either
      uncaging of GABA in the antennal lobes or the mushroom bodies during the CS
      presentation of the CS-US pairing impairs memory formation, while uncaging GABA
      during the US phase has no effect on memory. Uncaging GABA during the CS
      presentation in memory retrieval also has no effect. Thus, in honeybee appetitive
      olfactory learning GABA specifically interferes with the integration of CS and US
      during associative conditioning and exerts a modulatory role in memory formation
      depending on the training strength. 

PMID- 23860601
TI  - Sucrose responsiveness, learning success, and task specialization in ants.
AB  - Social insects possess remarkable learning capabilities, which are crucial for
      their ecological success. They also exhibit interindividual differences in
      responsiveness to environmental stimuli, which underlie task specialization and
      division of labor. Here we investigated for the first time the relationships
      between sucrose responsiveness, behavioral specialization, and appetitive
      olfactory learning in ants, including reproductive castes. We show that castes of
      the ant Camponotus aethiops differ in their responsiveness to sucrose and in
      their learning success in olfactory conditioning experiments in which sucrose is
      used as reward. Olfactory learning was better in foragers than in nurses, in
      agreement with their higher sucrose responsiveness. Interindividual variation in
      stimulus responsiveness and in learning may be, therefore, a crucial factor for
      division of labor in social insects. 

PMID- 23860602
TI  - The effect of pre-adapting light intensity on dark adaptation in early age
      related macular degeneration.
AB  - BACKGROUND: This study aimed to identify the pre-adapting light intensity that
      generated the maximum separation in the parameters of dark adaptation between
      participants with early age-related macular degeneration (AMD) and healthy
      control participants in the minimum recording time. METHODS: Cone dark adaptation
      was monitored in 10 participants with early AMD and 10 age-matched controls after
      exposure to three pre-adapting light intensities, using an achromatic annulus (12
      degrees  radius) centred on the fovea. Threshold recovery data were modelled, and
      the time constant of cone recovery (tau), final cone threshold, and time to rod
      cone-break (RCB) were determined. The diagnostic potential of these parameters at
      all pre-adapting intensities was evaluated by constructing receiver operating
      characteristic (ROC) curves. RESULTS: There were significant differences between
      those with early AMD and healthy controls in cone tau and time to RCB (p < 0.05)
      at all pre-adapting 'bleaching' intensities. ROC curves showed that the
      diagnostic potential of dark adaptometry was high following exposure to all three
      pre-adapting intensities, generating an area under the curve in excess of 0.87 +/
      0.08 for cone tau and time to RCB for all conditions. CONCLUSIONS: Dark
      adaptation was shown to be highly diagnostic for early AMD across a range of pre
      adapting light intensities, and therefore, the lower pre-adapting intensities
      evaluated in this study may be used to expedite dark adaptation measurement in
      the clinic without compromising the integrity of the data obtained. This study
      reinforces the suggestion that cone and rod dark adaptation are good candidate
      biomarkers for early AMD.

PMID- 23860603
TI  - Remnant liver volume-based predictors of postoperative liver dysfunction after
      hepatectomy: analysis of 625 consecutive patients from a single institution.
AB  - BACKGROUND: During hepatic resection, accurate estimation of remnant liver volume
      and hepatic function is crucial for avoiding postoperative liver failure. The
      purpose of this study was to identify preoperative factors related to
      postoperative liver dysfunction according to the percentage of future liver
      remnant volume (%FLR). METHODS: A total of 625 patients who underwent hepatectomy
      were enrolled in this study. Total bilirubin level >50 MUmol/L and/or prothrombin
      time index <50 % on postoperative day 5 were used as criteria for postoperative
      liver dysfunction (PLD). Patients were classified into 3 groups according to the
      %FLR: 35-60 (n = 116), 60-80 (n = 157), and >80 (n = 351). Multivariate logistic
      regression analysis was performed to identify factors related to postoperative
      liver dysfunction in each group. RESULTS: Among the patients with 35-80 %FLR, the
      morbidity and mortality rates were significantly higher in patients with PLD than
      in patients without PLD. There was no postoperative death in patients with >80
      %FLR . Multivariate analysis showed that PLD was associated with receptor index
      (LHL15) <=0.93 (odds ratio [OR] = 7.96) in patients with 35-60 %FLR. The
      sensitivity and specificity for PLD were 87.5 and 96.1 %, respectively. In
      patients with 60-80 %FLR, PLD was associated with platelet count <10.0 * 10(4)/mL
      (OR = 6.12). The sensitivity and specificity for PLD were 73.3 and 96.2 %,
      respectively. CONCLUSION: LHL15 <=0.93 and platelet count <10.0 * 10(4)/mL are
      pivotal indicators for predicting PLD in patients with 35-60 %FLR and 60-80 %FLR,
      respectively.

PMID- 23860604
TI  - MRI T2 hypointensity of metastatic brain tumors from gastric and colonic cancers.
AB  - BACKGROUND: Metastatic brain tumors from gastric and colon cancers are frequently
      revealed by hypointensity on T2-weighted magnetic resonance images (MRIs).
      However, the reason for this T2 hypointensity has yet to be clarified. We
      hypothesize that it is due to collagen deposition within the tissues. METHODS:
      Seven metastatic brain tumors, from 3 gastric cancers and 4 colon cancers were
      investigated. The degree of hypointensity of these tumors in T2-weighted images
      was quantitatively assessed as the ratio of gray-scale densities of tumor to
      brain using ImageJ. The result was compared with the amount of collagen in the
      resected specimens, which was quantified by ImageJ analysis software, utilizing
      the colour deconvolution method following Azan-Mallory staining. The degree of
      hypointensity was also compared with the ratio of viable epithelial component
      area/whole tissue area. Additionally, collagen distribution was studied by
      immunohistochemical staining. RESULTS: There was a clear negative correlation
      between intensity in T2-weighted images of these metastatic tumors and the amount
      of collagen they contained (R (2) = 0.766). However, there was no significant
      correlation between the T2 intensity and the ratio of viable epithelial
      component. Immunohistochemical analysis revealed that collagen types I, III, VII,
      X, and XI were expressed in the epithelial components and types IV, V, and VI
      were expressed in the stromal areas of the metastatic tumors. Collagen deposition
      was observed not only in stromal fibrous areas, but also in cytoplasmic areas in
      these metastatic tumors. CONCLUSIONS: Hypointensity of metastatic brain tumors
      arising from gastric and colonic cancers may be due to the accumulation of
      collagen in the tissues.

PMID- 23860605
TI  - Laparoscopic resection of paraaortic or paracaval lesions: feasibility and
      outcome.
AB  - BACKGROUND: Laparoscopic retroperitoneal lymph node dissection of paraaortic and
      paracaval lymph nodes is used to stage nonseminomatous germ cell tumors. Primary
      tumors can arise from the retroperitoneum, and tumors from nonurologic malignancy
      also may metastasize to retroperitoneal lymph nodes. This study aimed to describe
      the authors' experience with laparoscopic resection of these lesions. METHODS: A
      consecutive series of patients between January 2007 and June 2011 with
      paraaortic, aortocaval, or paracaval tumors with a maximum diameter smaller than
      10 cm and confined to the abdomen were considered for laparoscopic resection.
      Data were collected on size and pathology of the lesions, anesthesia time,
      postoperative stay, and postoperative morbidity and mortality. RESULTS: In this
      study, 25 patients with a median age of 49 years were assessed for laparoscopic
      resection. Eight patients were considered unsuitable for a laparoscopic approach
      because of tumor location (n = 5), previous retroperitoneal surgery (n = 1),
      stoma (n = 1), or lesion not clearly visible on computed tomography (n = 1). Of
      the 17 patients undergoing laparoscopic resection, 1 was found to have diffuse
      peritoneal disease at laparoscopy, whereas another was converted to an open
      procedure due to bleeding. All the laparoscopic patients had an R0 resection. The
      median hospital stay was significantly shorter in the laparoscopic group (2 days)
      than in the open group (6 days) (P = 0.009). One patient in the laparoscopic
      group with a functioning paraganglioma and advanced cardiac disease died on
      postoperative day 7. CONCLUSION: Laparoscopic paraaortic and paracaval surgery
      for primary and recurrent tumors of the retroperitoneum is feasible, with clear
      resection margin rates similar to that observed for open surgery.

PMID- 23860606
TI  - Rationale for the fundamental use of surgical EnergyTM (FUSE) curriculum
      assessment: focus on safety.
AB  - BACKGROUND: Almost all surgical procedures involve the use of devices that apply
      energy to tissue. Adverse events can occur if the devices are not used
      appropriately. The SAGES' Fundamental Use of Surgical EnergyTM (FUSE) program
      will include a curriculum and certification examination to address this safety
      issue. The aim of this study was to determine the self-perceived knowledge of
      practicing surgeons related to energy-based devices and identify areas to
      emphasize in the assessment component of FUSE. METHODS: Psychometric experts led
      the test development process. During a 2-day retreat, a multidisciplinary group
      defined 63 test objectives assessing the knowledge and skills required to use
      energy-based surgical instruments safely (job task analysis). A survey was sent
      to a sample of 103 SAGES leaders and others in the test target audience to
      determine the number of items to use for the certification examination.
      Participants rated each objective for frequency, relevance, and importance on a 1
      7 scale with the means used to create a weighted scale. The survey also included
      five self-assessment questions. RESULTS: Fifty surveys were completed; only 28 %
      of respondents considered themselves "experts." The most common source of
      knowledge was "industry sales representative or course" (42 %). The highest
      weighted topic was "Prevention of Adverse Events with Electrosurgery." The
      highest-rated objectives (>6 out of 7) were "Identify various mechanisms whereby
      electrosurgical injuries may occur," "Identify patient protection measures for
      setup and settings for the electrosurgical unit," and "Identify circumstances,
      mechanisms, and prevention of dispersive electrodes-related injury." CONCLUSIONS:
      Although basic and advanced energy-based devices are commonly used, training has
      been largely dependent upon industry representatives or industry-sponsored
      courses. Few surgeons consider themselves experts in the mechanisms of action and
      the appropriate and safe use of energy-based surgical devices. Competencies that
      emphasize electrosurgical safety were viewed as most important for the FUSE
      certification examination.

PMID- 23860607
TI  - Simulated Colonoscopy Objective Performance Evaluation (SCOPE): a non-computer
      based tool for assessment of endoscopic skills.
AB  - BACKGROUND: The Simulated Colonoscopy Objective Performance Evaluation (SCOPE)
      was developed to fill the need for a lower-cost, non-virtual-reality (VR)-based
      assessment tool. This study aimed to evaluate the ability of SCOPE to assess
      endoscopic skills objectively. METHODS: Four tasks were created using the Kyoto
      Kagaku colonoscopy model (Kyoto Kagaku Co., Ltd., Kyoto, Japan). The SCOPE tasks
      included Scope Manipulation (SM) requiring torque and tip deflection to align a
      shape in the colon with a matching shape on the monitor; Tool Targeting (TT)
      requiring coordination with biopsy forceps to contact a metal target; Loop
      Management (LM) requiring prevention, recognition, and reduction of a redundant
      sigmoid colon with navigation to the cecum; and Mucosal Inspection (MI) requiring
      identification of simulated polyps during withdrawal and retroflexion. Key
      performance metrics were identified, and a normalized scoring system was
      developed. For the study, 35 subjects were stratified into three cohorts based on
      colonoscopy experience: novice (0-50 colonoscopies; n = 11), intermediate (51-139
      colonoscopies; n = 13), and experienced (>140 colonoscopies; n = 11). The
      subjects performed two trials of all four tasks. RESULTS: Across all four tasks,
      the experienced endoscopists (E) consistently outperformed the intermediates (I),
      who in turn outperformed the novices (N). The mean normalized scores with 95 %
      confidence intervals (CI) are as follows: SM: N (54; range, 26-82), I (92; range,
      79-106), E (106; range, 93-118) (p = 0.0006). TT: N (40; range, 24-55), I (77;
      range, 63-91), E (88; range, 72-105) (p < 0.0001). LM: N (51; range, 24-79), I
      (80; range, 59-101), E (101; range, 98-105) (p = 0.003). MI: N (73; range, 53
      92), I (85; range, 76-95), E (100; range, 91-108) (p = 0.013). Total score: N
      (218; range, 155-280), I (335; range, 299-371), E (395; range, 371-419) (p <
      0.0001). The test-retest reliability (0.6) for the expert total score was
      respectable. CONCLUSIONS: The validity evidence from this study shows that scores
      on SCOPE tasks can differentiate between groups expected to have different levels
      of technical skill. This model shows promise as a low-technology tool for
      objective assessment or training of endoscopic skills.

PMID- 23860608
TI  - Current national practice patterns for inpatient management of ventral abdominal
      wall hernia in the United States.
AB  - BACKGROUND: The health-care burden related to ventral hernia management is
      substantial, with more than 3 billion dollars in expenditures annually in the US.
      Previous studies have suggested that the utilization of laparoscopic repair
      remains relatively low although national volume estimates have not been reported.
      We sought to estimate the inpatient national volume of elective ventral hernia
      surgery and characterize the proportion of laparoscopic versus open operations.
      METHODS: We analyzed data from the Nationwide Inpatient Sample to identify adults
      with a diagnosis of an umbilical, incisional, or ventral hernia who underwent an
      elective inpatient repair between 2009 and 2010. Cases that involved other major
      abdominal or pelvic operations were excluded. Covariates included patient
      demographics, surgical approach, and use of mesh. National surgical volume
      estimates were generated and length of stay and total hospital charges were
      compared for laparoscopic versus open repairs. RESULTS: A total of 112,070
      ventral hernia repairs were included in the analysis: 72.1 % (n = 80,793) were
      incisional hernia repairs, while umbilical hernia repairs comprised only 6.9 % (n
      = 7,788). Laparoscopy was utilized in 26.6 % (n = 29,870) of cases. Mesh was
      placed in 85.8 % (n = 96,265) of cases, including 49.3 % (n = 3,841) of umbilical
      hernia repairs and 90.1 % (n = 72,973) of incisional hernia repairs. Length of
      stay and total hospital charges were significantly lower for laparoscopic
      umbilical, incisional, and "other" ventral hernia repairs (p values all <0.001).
      Total hospital charges during this 2-year period approached 4 billion dollars
      ($746 million for laparoscopic repair; $3 billion for open repair). CONCLUSIONS:
      Utilization of laparoscopy for elective abdominal wall hernia repair remains
      relatively low in the US despite its excellent outcomes. Given the substantial
      financial burden associated with these hernias, future research focused on
      preventing the development and optimizing the surgical treatment of ventral
      abdominal wall hernias is warranted.

PMID- 23860609
TI  - Does prophylactic stent insertion to the common bile duct during endoscopic
      retrograde cholangiopancreatography (ERCP) before cholecystectomy have any impact
      on the rate of biliary complications?
AB  - BACKGROUND: Patients with choledochocystolithiasis generally undergo endoscopic
      sphincterotomy (ES) followed by elective cholecystectomy. They can experience the
      development of recurrent biliary events while waiting for their scheduled
      surgery. AIM: This study investigated whether stent insertion before
      cholecystectomy influences the rate of complications. METHODS: The study compared
      retrospective and prospective groups of patients with choledochocystolithiasis
      who underwent ES with or without prophylactic common bile duct stent insertion
      before cholecystectomy. The rate of emergency cholecystectomies and biliary
      complications during the waiting period before the elective procedure was
      analyzed. RESULTS: For the study, 162 patients with choledochocystolithiasis who
      underwent endoscopic retrograde cholangiopancreatography (ERCP) with ES were
      divided to two subgroups. Group A included 52 patients with stent insertion (mean
      age, 58.3 +/- 19.4 years), and group B included 110 patients with no stent
      insertion (mean age, 61.4 +/- 17.7 years) (p = 0.32). Males made up 33.3% of
      group A and 53.7% of group B (p = 0.018). The median time to elective
      cholecystectomy (open or laparoscopic) was 41.5 days for the patients without
      bile duct stent insertion before cholecystectomy and 53.5 days for the patients
      who had the stent insertion before cholecystectomy (p = 0.63). Repeat emergency
      ERCP due to acute cholangitis was 5.6% in group A and 1.0% in group B (p = 0.43).
      Emergency cholecystectomy rates due to acute cholecystitis after ES were 15.4% in
      group A and 14.5% in group B (p = 1.00). No mortality occurred. CONCLUSIONS:
      According to the study findings, prophylactic stent insertion during ERCP before
      cholecystectomy has no impact on biliary complications.

PMID- 23860611
TI  - Learning lessons for the future: assessments of demand and benefit are required
      in addition to training in single incision laparoscopic surgery. Response letter
      to: Pucher PH, Sodergren MH, Singh P, Darzi A, Parakseva P. Have we learned from
      lessons of the past? A systematic review of training for single incision
      laparoscopic surgery. Surg Endosc (2013) 27:1478-1484.

PMID- 23860610
TI  - Laparoscopic reversal of Roux-en-Y gastric bypass into normal anatomy with or
      without sleeve gastrectomy.
AB  - OBJECTIVE: This study was designed to describe and analyze the outcomes after
      laparoscopic reversal to normal anatomy (NA) with or without concomitant "sleeve
      gastrectomy" (SG), after Roux-en-Y gastric bypass (RYGB). Reversal has been
      proposed as corrective strategy after RYGB. METHODS: We propose a retrospective
      analysis of a prospectively kept database. RESULTS: From January 2005 to October
      2012, 20 female patients underwent laparoscopic reversal after RYGB for one or
      more of the following conditions: hypoglycaemic syndrome (nine patients), weight
      regain (six patients), severe dumping (six patients), and cachexia (two
      patients). Preoperative BMI was 28.0 (19.2-40.3) kg/m2. Reversal was performed to
      NA in ten patients and included a SG procedure in another ten. Postoperative
      complications included one bleeding and three leaks (15%; all in SG patients).
      Mean hospital stay was 7 days. Mortality was 0. With a mean follow-up of 11.5
      months, all but one patient recovered from their initial condition. However,
      three developed severe gastroesophageal reflux disease (GERD) symptoms and three
      had chronic diarrhoea. CONCLUSIONS: Outcomes of laparoscopic reversal of RYGB are
      good, but complications may occur when SG is added. The surgical alterations
      caused by the reversal may explain the GERD or diarrhoea experienced by some
      patients.

PMID- 23860612
TI  - Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ
      cell tumors: long-term efficacy and safety outcomes.
AB  - BACKGROUND: Since 1985, we introduced a modified combination of etoposide,
      ifosfamide, and cisplatin (PEI) as second-line therapy of adult male germ cell
      tumors with the aim to reduce toxic effect while maintaining efficacy over the
      original regimen. PATIENTS AND METHODS: Patients received four cycles of
      ifosfamide at 2.5 g/m(2) on days 1-2, etoposide, and cisplatin at 100 and 33
      mg/m(2), respectively, on days 3-5 every 21 days, followed by surgery. Results
      were stratified according to the International Germ Cell Consensus Classification
      Group-2 (IGCCCG-2). RESULTS: From February 1985 to January 2012, 189 patients
      were treated. 72.6% were IGCCCG-2 intermediate-to-very high risk. Thirty-five
      patients (18.5%) had a complete response, 67 (35.4%) a marker normalization (PRm
      ). Median follow-up was 122.1 months (inter-quartile range [IQR]: 71.4-232.0).
      Two-year progression-free and 5-year overall survival were 34.3% [95% confidence
      interval (CI) 28.1% to 41.9%] and 42.1% (95% CI 35.3% to 50.2%), respectively.
      Survival estimates compared favorably with those obtained by conventional dose
      chemotherapy (CDCT) regimens in each prognostic category. 70.4% of grade 3-4
      neutropenia (25.5% febrile neutropenia), 48.1% thrombocytopenia, 21.2% anemia,
      3.2% neurotoxic effect, and no severe renal toxic effect were recorded.
      CONCLUSION: Dose-modified Italian PEI should be considered as an appropriate
      benchmark for CDCT in the first salvage setting.

PMID- 23860613
TI  - Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical
      Practice Guidelines for diagnosis, treatment and follow-up.

PMID- 23860614
TI  - Transcatheter closure of patent ductus arteriosus and atrial septal defect
      without on-site surgical backup: a two-year experience in an African community.
AB  - Congenital heart disease contributes significantly to the health burden of
      children in Nigeria. Interventions for congenital heart disease have been
      available in the developed world since the first report on device closure of
      patent ductus arteriosus (PDA) in 1967 by Porstmann. However, this did not start
      in Nigeria until October 2010. This study aimed to document the profiles of the
      patients who had undergone interventions for congenital heart diseases since the
      availability of the procedure, the challenges encountered, and the prospects
      associated with the interventions at the study site. All the patients referred to
      undergo interventions for congenital heart disease at the study center between
      October 2010 and 2012 were studied. The profile of the patient, including
      diagnosis at referral, indication for interventions, and interventions performed,
      were documented. The patients ranged in age from 3 to 62 years (mean age, 13.54
      +/- 17.7 years), and the male-to-female ratio was 1:3. The diagnosis at referral
      included PDA in 10 (83 %) of the 12 patients and secundum atrial septal defect in
      2 patients (17 %). They all had transcatheter closure of the defects.
      Interventional procedures for congenital heart diseases currently are available
      locally, but the high degree of manpower training required, the cost, and the
      local availability of consumables are major factors limiting their use. Regional
      and international collaboration could be mutually beneficial. 

PMID- 23860617
TI  - Boronic acid-containing hydrogels: synthesis and their applications.
AB  - Boronic acid-containing hydrogels are important intelligent materials. With the
      introduction of boronic acid functionality, these hydrogels exhibit a lot of
      interesting properties, such as glucose-sensitivity, reversibility and self
      healing. These materials have found important applications in many areas,
      especially in biomedical areas. This paper aims to provide an overview of the
      current state of the art of the study in this area. We review the synthesis and
      properties of various boronic acid-containing hydrogels, including macroscopic
      hydrogels, microgels and layer-by-layer self-assembled films. Their applications
      were described, with an emphasis on the design of various glucose sensors and
      self-regulated insulin delivery devices. New development in this area was
      highlighted. Problems and the new directions were discussed. 

PMID- 23860616
TI  - On-Q (r) pain pump versus epidural for postoperative analgesia in children.
AB  - PURPOSE: The On-Q((r)) pain pump provides a continuous infusion of local
      anesthesia for management of postoperative pain. The objective of this study was
      to assess the efficacy and outcomes of the On-Q((r)) pump compared to continuous
      epidural in children postoperatively. METHODS: We performed a retrospective
      review of patients in our hospital who received a postoperative epidural or On
      Q((r)) pump from 2005 to 2008. Patients were sub-categorized by incision type.
      RESULTS: Seventy patients received epidural and 66 On-Q((r)). On-Q((r)) therapy
      was longer by 1 day (p < 0.0001), but did not affect postoperative length of
      stay. Patients with On-Q((r)) pumps had a decreased rate of Foley catheter
      placement (p = 0.002) and shorter duration of catheter use by more than a day (p
      < 0.001). Moderate to severe pain was similar in the two groups on postoperative
      days 0-5. Supplemental narcotic use was higher in the On-Q((r)) group only on
      postoperative day 1 (p = 0.005) and in patients with midline and transverse
      abdominal incisions. No differences were seen in time to ambulation or recovery
      of postoperative ileus. CONCLUSION: The On-Q((r)) pain pump is an effective
      method for postoperative pain control, without the inherent risks of epidural
      catheters.

PMID- 23860618
TI  - Changes in the diagnosis of autism: how parents and professionals act and react
      in France.
AB  - The category of autism has undergone huge changes over the past 20 years. This
      study was undertaken to analyze the changes and how parents have experienced the
      diagnostic process in France. Data were obtained from in-depth interviews with
      parents and psychiatrists, and from 248 questionnaires with open-ended questions
      filled in by parents. We compared the experiences of parents with adult autistic
      children to those of parents with young autistic children. Progressively earlier
      age at diagnosis was evidenced. These changes occurred later than in North
      America and the UK, due to the reluctance of French professionals to adopt the
      new classifications of diseases which they viewed as undervaluing both the
      physician's holistic clinical skills, and psychoanalytical interpretations.
      Parents' experiences and interviews with psychiatrists were analyzed in order to
      document changes over time in the diagnostic process following tensions between
      parents and professionals, and intra-professional debates in psychiatry. Our data
      support the notion that the diagnosis of autism is historically and nationally
      contingent. The interactions between changes in the diagnostic process, policy,
      and parental experiences have led to changes in the way autism is defined,
      understood, and experienced.

PMID- 23860619
TI  - Putative factors associated with molar incisor hypomineralisation: an
      epidemiological study.
AB  - AIM: The aim of the study was to examine the aetiological factors involved in the
      development of molar incisor hypomineralisation (MIH). METHODS: The study
      population comprised 4,049 children (2,029 girls, 2020 boys) aged 7-12 years.
      Children were examined for MIH in the school environment. Putative aetiological
      factors were evaluated using a questionnaire sent to children's families. The
      questionnaire included questions on prenatal, perinatal, and postnatal systemic
      conditions. Multivariate analysis was performed using multiple logistic
      regression, and Pearson's Chi-square test was used to evaluate nominal or ordinal
      variables with Fisher's exact test used in cases of small sample sizes. A level
      of p < 0.05 was considered statistically significant. RESULTS: MIH was observed
      in 7.7 % of the study population. A total of 3,827 completed questionnaires were
      returned, yielding a response rate of 95.3 %. MIH was found to be associated with
      prematurity (7 %), gastrointestinal problems (3.9 %), pneumonia (6.3 %), frequent
      fever (26.1 %), measles (14.7 %), and chickenpox (29.3 %) before age 4 years.
      STATISTICS: Prevalence did not vary significantly between girls and boys (p >
      0.05). Prematurity, gastrointestinal problems, pneumonia, frequent high fever,
      measles, and chickenpox before age 4 years were found to be significantly related
      with MIH (p < 0.05). CONCLUSIONS: The aetiology of MIH is not clear yet, and the
      results of this study support the results of previous studies regarding the
      putative causal effect of several factors.

PMID- 23860620
TI  - Ankyloglossia and tongue mobility.
AB  - AIM: Ankyloglossia or tongue-tie is a congenital condition of newborns when the
      inferior lingual fraenulum is too short and is attached to the tip of the tongue
      limiting its movement. The aim of this study was to evaluate the relationship
      between ankyloglossia classification and tongue mobility. In addition, the
      prevalence of ankyloglossia among males and females was assessed. METHODS: 300
      subjects (150 boys and 150 girls) with an age range of 7-12 years were randomly
      selected from different schools. The distance between the uppermost point of
      lingual fraenulum and its insertion into the oral floor was measured in the
      subjects. The subjects were categorised from having no ankyloglossia to severe
      tongue-tie based on the measurements. RESULTS AND CONCLUSION: This study showed
      that ankyloglossia was more common in males. It also showed that only subjects
      with a lingual fraenulum of <1.5 cm suffered from inadequate tongue movement.

PMID- 23860621
TI  - Molar-incisor hypomineralisation: a prevalence study amongst primary
      schoolchildren of Shiraz, Iran.
AB  - AIM: To investigate the prevalence of molar-incisor hypomineralisation (MIH)
      amongst primary schoolchildren of Shiraz, Iran, taking into account the possible
      influence of biographic and socio-demographic parameters. STUDY DESIGN AND
      METHODS: A randomised cluster sample of 9- to 11-year-old children (N = 810) had
      their first permanent molars and incisors (index teeth) evaluated using the
      European Academy of Paediatric Dentistry criteria for MIH. The examinations were
      conducted at schools by a calibrated examiner. Prevalence of MIH was assessed
      based on biographic and socio-demographic parameters including area of residency,
      school type, father's level of education, weight-for-age and height-for-age.
      RESULTS AND STATISTICS: Of the children examined, 164/810 (20.2%) had MIH and
      53.7% of them presented with MIH lesions in all first molars. Mild defects
      represented by demarcated yellow brown opacities comprised 35.5% of the total MIH
      lesions. The prevalence of MIH was significantly greater in girls, children with
      healthy body weight and height, those whose fathers did not have a tertiary
      education and from families of low socio-economic status. Regression analyses
      indicated that none of the biographic and socio-demographic variables represented
      a significant risk factor in the occurrence of MIH except for body weight.
      Obesity was negatively correlated to MIH (OR = 0.45; 95% CI 0.25-0.82).
      CONCLUSIONS: The prevalence of MIH in a group of Iranian children was 20.2%.
      Biographic and socio-demographic parameters appeared to have no significant
      correlation with MIH except body weight, which warrants further research.

PMID- 23860622
TI  - The CTLA4 +49A/G polymorphism is associated with an increased risk of Hashimoto's
      thyroiditis in Asian but not Caucasian populations: an updated meta-analysis.
AB  - The polymorphism +49A/G in the cytotoxic T lymphocyte-associated antigen 4 (CTLA
      4) gene has been implicated in susceptibility to Hashimoto's thyroiditis (HT),
      but the findings are not clear-cut. This study aimed to investigate the
      association between CTLA-4 polymorphisms and HT risk using an updated meta
      analysis. A meta-analysis was carried out of 14 previous studies that
      investigated the CTLA-4 +49A/G polymorphism and HT risk. +49A/G was associated
      with a significantly increased HT risk in both allele analysis and all genetic
      models (allele analysis: G vs. A: P < 0.001, OR = 1.379, 95 % CI = 1.244-1.529).
      Subgroup analysis by ethnicity showed a significantly increased HT risk with the
      G allele and all other genetic models in the Asian subgroup (P < 0.001). In the
      Caucasian subgroup, no significant association was detected between the CTLA-4
      +49 G allele and HT, or in the genetic model analysis (P = 0.05). This gene-based
      analysis indicates that the cumulative effect of the +49A/G polymorphism in CTLA
      4 is associated with HT in Asians, but appears to have no effect on HT in
      Caucasians.

PMID- 23860623
TI  - Expression of hedgehog signalling pathway in anaplastic thyroid cancer.
AB  - The purpose of this work is to study the activation of the hedgehog signalling
      pathway is associated with tumour progression in various types of cancer, hence
      the development of specific antagonists raises hope for new therapeutic
      strategies. Therefore, the expression of hedgehog pathway components in
      anaplastic thyroid cancer (ATC) and effects of the hedgehog inhibitor Cyclopamine
      on ATC cells were investigated in this study. Expression of the ligand Sonic
      Hedgehog (SHh), the transmembrane protein Smoothened (Smo), the receptor Patched
      (Ptc) and the target gene Gli-1 was evaluated in two ATC cell lines (Hth 74,
      C643) by RT-PCR and in tumour specimens by immunohistochemistry. The
      corresponding gene products were examined by western blotting analysis. After
      treatment with different concentrations of Cyclopamine the time-dependent course
      of cell viability in ATC cell lines was evaluated by MTT assay. SHh, Smo, Ptc and
      Gli were clearly expressed on mRNA and protein levels in both cell lines and in
      tumour samples (41 %SHh, 65 %Smo, 65 %Ptc and 65 %Gli). Treatment with
      Cyclopamine showed a time- and dose-dependent inhibition of cell numbers with
      IC50 values between 1 and 4 MUM in both cell lines, comparable to other types of
      cancer. In conclusion, we believe that the hedgehog pathway is expressed in
      anaplastic thyroid carcinoma specimens and proliferation of ATC cell lines can be
      influenced by the Hh inhibitor Cyclopamine. Aberrant activation of this pathway
      might be involved in the aggressive biology of anaplastic cancer and further
      evaluation regarding a possible clinical impact of pathway inhibition is
      warranted.

PMID- 23860624
TI  - An age-tailored intervention sustains physical activity changes in older adults:
      a randomized controlled trial.
AB  - BACKGROUND: A randomized controlled trial compared an age-tailored intervention
      to increase physical activity levels in older adults to an age-neutral
      intervention. PURPOSE: Both interventions communicated activity planning
      strategies and messages to improve self-efficacy. On top of this, the age
      tailored intervention also included two lifespan components that targeted present
      orientation and emotional focus, and fostered strategies of selection,
      optimization, and compensation. METHOD: A total of 386 German older adults (aged
      60-95 years) were randomized to receive either the age-tailored intervention (age
      specific strategy training and short-term emotional focus) or the age-neutral
      intervention. Physical activity was measured by questionnaires at baseline (T1)
      and at 6-month (T2) and 12-month follow-ups (T3). Latent true change modeling was
      applied by creating latent change scores (T2 - T1 and T3 - T2). RESULTS: After
      controlling for gender, age, and physical and mental health, allocation to the
      age-tailored intervention predicted a latent physical activity difference at T3 -
      T2, but not at T2 - T1. CONCLUSION: Compared to the age-neutral intervention, the
      age-tailored intervention led to superior maintenance of physical activity within
      these older adults.

PMID- 23860625
TI  - Floquet bound states in the continuum.
AB  - Quantum mechanics predicts that certain stationary potentials can sustain bound
      states with an energy buried in the continuous spectrum of scattered states, the
      so-called bound states in the continuum (BIC). Originally regarded as
      mathematical curiosities, BIC have found an increasing interest in recent years,
      particularly in quantum and classical transport of matter and optical waves in
      mesoscopic and photonic systems where the underlying potential can be judiciously
      tailored. Most of our knowledge of BIC is so far restricted to static potentials.
      Here we introduce a new kind of BIC, referred to as Floquet BIC, which
      corresponds to a normalizable Floquet state of a time-periodic Hamiltonian with a
      quasienergy embedded into the spectrum of Floquet scattered states. We discuss
      the appearance of Floquet BIC states in a tight-binding lattice model driven by
      an ac field in the proximity of the dynamic localization regime. 

PMID- 23860626
TI  - [Mechanical recanalization. There is one last chance! For].

PMID- 23860627
TI  - [Mechanical recanalization. There is one last chance! Against].

PMID- 23860629
TI  - Can postoperative complications be predicted by a routine CT scan on day 5? A
      study of 78 laparoscopic colorectal resections.
AB  - BACKGROUND: Postoperative computed tomography (CT) scan patterns after colorectal
      resection are difficult to analyze for both clinicians and radiologists. This
      study aimed to assess the role of single CT scan on postoperative day 5 in
      predicting postoperative morbidity. METHODS: From October 2007 to August 2009, 78
      patients undergoing laparoscopic colorectal resection were enrolled in a research
      study involving a routine contrast-enhanced multi-detector CT scan on
      postoperative day 5. Two groups were defined: patients with intra-abdominal
      postoperative morbidity requiring specific management, i.e., surgical or
      radiological procedure, and/or antibiotic therapy ("complications" group), and
      patients with uneventful postoperative outcome ("uneventful" group). CT findings
      were compared between the two groups with Fisher's exact test or chi-square test.
      RESULTS: Postoperative abdominal complications occurred in 16 patients (21 %). Of
      the CT findings on day 5, pneumonia, pulmonary embolism, portal or mesenteric
      thrombosis, operative area fat infiltration, peritoneal effusion,
      pneumoperitoneum, intra-abdominal collection, parietal inflammation or
      collection, and subcutaneous emphysema were observed in both groups without any
      significant difference. Only small bowel distension [25 % (4/16) in the
      "complications" group vs. 5 % (3/62) in the "uneventful" group; p = 0.029] and
      pleural effusion [81 % (13/16) vs. 48 % (30/62); p = 0.024, respectively] were
      observed significantly more often in the "complications" group. CONCLUSIONS: This
      study suggested that abdominal complications cannot be predicted by a CT scan on
      day 5 after laparoscopic colorectal resection. Thus, it cannot be recommended for
      routine use.

PMID- 23860630
TI  - Brain tumor detection and segmentation in a CRF (conditional random fields)
      framework with pixel-pairwise affinity and superpixel-level features.
AB  - PURPOSE: Detection and segmentation of a brain tumor such as glioblastoma
      multiforme (GBM) in magnetic resonance (MR) images are often challenging due to
      its intrinsically heterogeneous signal characteristics. A robust segmentation
      method for brain tumor MRI scans was developed and tested. METHODS: Simple
      thresholds and statistical methods are unable to adequately segment the various
      elements of the GBM, such as local contrast enhancement, necrosis, and edema.
      Most voxel-based methods cannot achieve satisfactory results in larger data sets,
      and the methods based on generative or discriminative models have intrinsic
      limitations during application, such as small sample set learning and transfer. A
      new method was developed to overcome these challenges. Multimodal MR images are
      segmented into superpixels using algorithms to alleviate the sampling issue and
      to improve the sample representativeness. Next, features were extracted from the
      superpixels using multi-level Gabor wavelet filters. Based on the features, a
      support vector machine (SVM) model and an affinity metric model for tumors were
      trained to overcome the limitations of previous generative models. Based on the
      output of the SVM and spatial affinity models, conditional random fields theory
      was applied to segment the tumor in a maximum a posteriori fashion given the
      smoothness prior defined by our affinity model. Finally, labeling noise was
      removed using "structural knowledge" such as the symmetrical and continuous
      characteristics of the tumor in spatial domain. RESULTS: The system was evaluated
      with 20 GBM cases and the BraTS challenge data set. Dice coefficients were
      computed, and the results were highly consistent with those reported by Zikic et
      al. (MICCAI 2012, Lecture notes in computer science. vol 7512, pp 369-376, 2012).
      CONCLUSION: A brain tumor segmentation method using model-aware affinity
      demonstrates comparable performance with other state-of-the art algorithms.

PMID- 23860631
TI  - [Spinal cord stimulation in 1974 in Germany: Innovation in pain therapy and
      primer for the "German-speaking chapter" of the IASP].

PMID- 23860632
TI  - [Self-rated pain sensitivity and postoperative pain].
AB  - OBJECTIVES: Pain sensitivity is a risk factor for postoperative pain and is
      usually determined by experimental pain stimulation. Ruscheweyh et al. (Pain
      146:65-74, 2009) developed the pain sensitivity questionnaire (PSQ) which
      assesses general pain sensitivity by self-rating without using extensive and
      painful experimental stimulation. The objective of this study was to examine
      whether subjective pain sensitivity affects postoperative pain intensity and can
      be considered as a risk factor for postoperative pain. MATERIALS AND METHODS:
      After obtaining informed consent 162 patients were enrolled in the study.
      Subjective pain sensitivity was assessed prior to surgery by using the PSQ. With
      respect to the results patients were classified into one of three groups (low,
      medium and high pain sensitivity). Primary outcome was postoperative pain
      intensity measured by numerical rating scales (NRS) on the first and second days
      after surgery. Other variables concerned administration of analgesics and patient
      satisfaction. The psychological control variables stress coping (SVF-48) as well
      as depression and anxiety (HADS-D) were also examined using the appropriate
      questionnaire. RESULTS: Patients with high pain sensitivity reported
      significantly higher postoperative pain than patients with low pain sensitivity.
      This result remained significant considering negative coping styles as a
      covariate. Patients with high pain sensitivity reported a stronger increase of
      pain intensity from resting in bed to moving in bed (effect size= 1.17) as
      compared to patients with low pain sensitivity (effect size= 0.77). Stronger pain
      (NRS > 4) was reported significantly more often by patients with high pain
      sensitivity. Furthermore, the patient group with low pain sensitivity reported
      the highest satisfaction with their own health recovery. CONCLUSIONS: Subjective
      pain sensitivity can easily be measured by the PSQ and is a risk factor for
      postoperative pain intensity.

PMID- 23860633
TI  - [Administrative prevalence, treatment and costs of somatoform pain disorder.
      Analysis of data of the BARMER GEK for the years 2008-2010].
AB  - INTRODUCTION: Data on administrative prevalence, types of treatment and disease
      costs of patients diagnosed with somatoform pain disorder (according to ICD 10)
      in Germany were not previously available. MATERIALS AND METHODS: We analysed
      health insurance data from 2008-2010 of 8.5 million people of the German
      statutory health insurance company BARMER GEK on administrative prevalence of
      insurants with at least one billing code F 45.4x in 2009 and at least one second
      billing code F 45.4x in the time period 2008-2010 stratified by age and gender,
      different professions being involved in treatment, diagnostics and treatment
      methods applied. The types and costs of out-patient treatment and of in-patient
      treatment in case of any discharge with diagnosis of F45.4 were analysed.
      RESULTS: The administrative prevalence doubled from 2008 to 2010 after the
      separation of the previous code F45.4 into F45.40 and F45.41. In 2009, 0.5 % of
      the insurants were diagnosed with F 45.4, whereby F 45.4 was diagnosed 2.3-fold
      more often in women than in men. Family practitioners (41 %) and
      anaesthesiologists (28 %) were the leading specialties in the care of chronic
      patients. In 2009, 54 % of patients underwent x-ray examination, 25 % magnetic
      resonance imaging and 11 % computed tomography. In all, 66 % of the chronic
      patients received basic psychosomatic care, 38 % were prescribed opioids, 12 %
      underwent spinal nerve anaesthesia and 14 % received psychotherapy. In 2009, the
      average direct and indirect treatment costs per patient with somatoform pain
      disorder were 5500 <euro>. CONCLUSION: Insurants diagnosed with somatoform pain
      disorder were probably overtreated with radiology and invasive procedures and
      with opioids.

PMID- 23860634
TI  - [Cross-sectional field 14 pain medicine. Implementation of the German Pain
      Society (DGSS) core curriculum in the model study course MaReCuM].
AB  - BACKGROUND: The recent introduction of amendments to the medical licensure laws
      led to the introduction of the field of pain medicine into the study program
      "Human Medicine". The implementation has to be completed by all medical faculties
      before 2016. MATERIAL AND METHODS: Pain medicine was implemented into the model
      study course"MaReCuM" at the medical faculty in Manheim as a compulsory subject
      in the year 2010. It is structured into five sections in a longitudinal manner.
      The core section is the "pain awareness week" in the fifth academic year of the
      medical studies. The content and structure is based on the German Pain Society
      (DGSS) curriculum. For the purpose of this study the examination results and the
      student evaluation forms from the academic years 2010/2011 and 2011/2012 were
      analyzed. RESULTS: The students regarded pain medicine as being highly relevant
      concerning its impact on the professional activities. The competence to develop a
      specific and individual therapy was of special interest. A good coordination of
      the contents of teaching between preclinical and clinical teaching was considered
      to be of major importance. CONCLUSIONS: The DGSS curriculum is a useful tool for
      the implementation of pain medicine in a study program. In order to improve
      access to basic pain medicine in general, a combined teaching program consisting
      of pain medicine and general medicine could be helpful. Pain medicine could be
      used as a guide for teaching contents of outpatient medicine.

PMID- 23860635
TI  - Discordant radiologic and histological dimensions of the zone of provisional
      calcification in fetal piglets.
AB  - BACKGROUND: Studies have shown that the fracture plane of the classic metaphyseal
      lesion (CML) of infant abuse occurs in the region of the primary spongiosa,
      encompassing a radiodense fracture fragment customarily referred to as the "zone
      of provisional calcification" or ZPC. However, the zone of provisional
      calcification is defined differently in the pathology and the imaging literature,
      potentially impeding efforts to understand the fundamental morphological features
      of the classic metaphyseal lesion. OBJECTIVE: We systematically correlated micro
      CT data with histology in piglets to explore the differing definitions of the
      zone of provisional calcification and to elucidate the anatomical basis for
      divergent definitions. MATERIALS AND METHODS: The distal tibias of five normal
      fetal piglets were studied postmortem. The specimens were resected and imaged
      with digital radiography (50 MUm resolution) and micro-CT (45 MUm(3) isotropic
      resolution). Image processing techniques were applied to the micro-CT data for
      visualization and data analysis. The resected tissue specimens were then
      processed routinely and the light microscopic features were correlated with the
      imaging findings. RESULTS: The longitudinal dimension of the radiologic zone of
      provisional calcification is greater than the histological ZPC, and these
      dimensions are statistically distinct (P < 0.0002). The radiologic zone of
      provisional calcification consists of two adjoining mineralized discoid regions
      that span the chondro-osseous junction-a thick discoid region that encompasses
      the densest region of the primary spongiosa, and a thin discoid region
      (corresponding to the histological ZPC) that is situated in the base of the
      physis adjacent to the metaphysis. CONCLUSION: The correlation of the normal
      histology and micro-CT appearance of this dynamic and complex region provides an
      anatomical foundation upon which a deeper appreciation of the morphology of the
      classic metaphyseal lesion can be built.

PMID- 23860636
TI  - Renal Doppler evaluation in the child with hypertension: a reasonable screening
      discriminator?
AB  - BACKGROUND: Hypertension is diagnosed in 1-5% of children, and 5-10% of those
      hypertensive children have renovascular disease. The gold standard for a
      diagnosis of renal artery stenosis is arteriography, and Doppler ultrasound
      (Doppler US) continues to be advocated as a useful screening test. OBJECTIVE: The
      purpose of this study was to determine the utility of Doppler US in children as a
      screening tool and to better define clinical features of children in whom
      arteriography should be performed. MATERIALS AND METHODS: This retrospective
      study evaluated the imaging and clinical parameters for all children who had a
      renal US with Doppler followed by a diagnostic arteriogram for the evaluation of
      hypertension during a 12-year period at a tertiary children's hospital. Sixty-two
      children were included. We evaluated each child's clinical parameters and placed
      each child into one of three categories of hypertension: mild, moderate or
      severe. RESULTS: Eleven of 17 kidneys with proven renal artery stenosis were
      detected with Doppler US (sensitivity 64%). Six children with renal artery
      stenosis were missed by Doppler US, four of whom had segmental artery lesions. Of
      the children with positive renal artery stenosis on arteriography, all but three
      (79%) were classified as having moderate to severe hypertension. CONCLUSION:
      Doppler US is a useful screening examination when evaluating children with
      hypertension, detecting renal artery stenosis in most affected children. The
      clinical risk classifications are helpful in guiding which children should
      proceed with arteriography regardless of the Doppler US results.

PMID- 23860637
TI  - Secondary synovial osteochondromatosis of the ankle in a child.
AB  - We describe a case of a large intra-articular ossifying mass of the ankle joint
      in a 12-year-old boy who sustained a severe ankle twisting injury at 6 years of
      age. The mass is presumed to be the result of secondary synovial
      osteochondromatosis originated from a fractured osteochondral fragment of the
      medial tubercle of the posterior process of the talus. The mass could be
      differentiated from os trigonum syndrome, Trevor disease and primary synovial
      osteochondromatosis based on its location, size and radiologic and histological
      features. 

PMID- 23860638
TI  - Poly(2-oxazoline) functionalized surfaces: from modification to application.
AB  - Poly(2-oxazoline)s (POxs) are a versatile class of biocompatible polymers, which
      have been investigated as poly(ethylene glycol) (PEG) alternatives. In recent
      years, POxs have drawn significant attention as coatings for antifouling
      applications. In this tutorial review different approaches to immobilize POxs on
      surfaces as well as properties and applications of POx coated surfaces will be
      presented. 

PMID- 23860640
TI  - Problems with using mechanisms to solve the problem of extrapolation.
AB  - Proponents of evidence-based medicine and some philosophers of science seem to
      agree that knowledge of mechanisms can help solve the problem of applying results
      of controlled studies to target populations ('the problem of extrapolation'). We
      describe the problem of extrapolation, characterize mechanisms, and outline how
      mechanistic knowledge might be used to solve the problem. Our main thesis is that
      there are four often overlooked problems with using mechanistic knowledge to
      solve the problem of extrapolation. First, our understanding of mechanisms is
      often (and arguably, likely to remain) incomplete. Secondly, knowledge of
      mechanisms is not always applicable outside the tightly controlled laboratory
      conditions in which it is gained. Thirdly, mechanisms can behave paradoxically.
      Fourthly, as Daniel Steel points out, using mechanistic knowledge faces the
      problem of the 'extrapolator's circle'. At the same time, when the problems with
      mechanistic knowledge have been addressed, such knowledge can and should be used
      to mitigate (nothing can entirely solve) the problem of extrapolation. 

PMID- 23860639
TI  - Innovative pharmaceutical development based on unique properties of nanoscale
      delivery formulation.
AB  - The advent of nanotechnology has reignited interest in the field of
      pharmaceutical science for the development of nanomedicine. Nanomedicinal
      formulations are nanometer-sized carrier materials designed for increasing the
      drug tissue bioavailability, thereby improving the treatment of systemically
      applied chemotherapeutic drugs. Nanomedicine is a new approach to deliver the
      pharmaceuticals through different routes of administration with safer and more
      effective therapies compared to conventional methods. To date, various kinds of
      nanomaterials have been developed over the years to make delivery systems more
      effective for the treatment of various diseases. Even though nanomaterials have
      significant advantages due to their unique nanoscale properties, there are still
      significant challenges in the improvement and development of nanoformulations
      with composites and other materials. Here in this review, we highlight the
      nanomedicinal formulations aiming to improve the balance between the efficacy and
      the toxicity of therapeutic interventions through different routes of
      administration and how to design nanomedicine for safer and more effective ways
      to improve the treatment quality. We also emphasize the environmental and health
      prospects of nanomaterials for human health care. 

PMID- 23860641
TI  - A phase Ib combination study of RO4929097, a gamma-secretase inhibitor, and
      temsirolimus in patients with advanced solid tumors.
AB  - BACKGROUND: To determine the recommended phase II dose (RP2D) and assess the
      safety, pharmacokinetics (PKs) and pharmacodynamics of RO4929097in combination
      with temsirolimus. METHODS: Escalating doses of RO4929097 and temsirolimus were
      administered at three dose levels. Patients received once daily oral RO4929097 on
      a 3 days on/4 days off schedule every week, and weekly intravenous temsirolimus.
      Blood samples were collected for PK analysis. Archival tissue specimens were
      collected for Notch pathway biomarker analysis and genotyping of frequent
      oncogenic mutations. RESULTS: Seventeen patients with refractory advanced solid
      tumors were enrolled in three dose levels (DLs): DL1 (RO4929097 10 mg;
      Temsirolimus 25 mg), DL2 (RO4929097 20 mg; Temsirolimus 25 mg), and DL3
      (RO4929097 20 mg; Temsirolimus 37.5 mg). The most common toxicities related to
      the study drug combination included: fatigue (82 %; grade 3 6 %), mucositis, (71
      %; grade 3 6 %), neutropenia (59 %; grade 3 12 %), anemia (59 %; grade 3 0 %),
      and hypertriglyceridemia (59 %; grade 3 0 %). Two dose-limiting toxicities, grade
      3 rash and grade 3 mucositis, were observed in the same patient in the first dose
      level prompting dose expansion. Eleven patients (73 %) had stable disease as
      their best response. Co-administration of RO4929097 was associated with increased
      clearance and reduced exposure to temsirolimus, suggestive of drug-drug
      interaction via CYP3A4 induction. No correlation between the expression of Notch
      pathway biomarkers or genotype and time to progression was noted. CONCLUSIONS:
      RO4929097 can be safely combined with temsirolimus in patients with advanced
      solid tumors. The RP2D was established at 20 mg of RO4929097 combined with 37.5
      mg of temsirolimus.

PMID- 23860642
TI  - A phase I study of AT-101 with cisplatin and etoposide in patients with advanced
      solid tumors with an expanded cohort in extensive-stage small cell lung cancer.
AB  - BACKGROUND: A phase I, dose-escalation study of AT-101 with cisplatin and
      etoposide was conducted to determine the maximum tolerated dose (MTD)/recommended
      phase 2 dose (RP2D), safety and pharmacokinetics in patients with advanced solid
      tumors, with an expanded cohort in patients with extensive-stage small cell lung
      cancer (ES-SCLC) to assess preliminary activity. METHODS: In the dose escalation
      portion, increasing doses of AT-101 were administered orally BID on days 1-3
      along with cisplatin on day 1 and etoposide on days 1-3 of a 21 day cycle. At the
      RP2D, an additional 7 patients with untreated ES-SCLC were enrolled. RESULTS:
      Twenty patients were enrolled in the dose-escalation cohort, and 7 patients with
      ES-SCLC were enrolled in the expanded cohort. The MTD/RP2D was established at AT
      101 40 mg BID days 1-3 with cisplatin 60 mg/m2 and etoposide 120 mg/m2 on day 1
      of a 21 day cycle with pegfilgrastim support. Two DLTs of neutropenic fever were
      seen at dose level 1. After the addition of pegfilgrastim, no additional DLTs
      were observed. Grade 3/4 treatment-related toxicities included: diarrhea,
      increased AST, neutropenia, hypophosphatemia, hyponatremia, myocardial infarction
      and pulmonary embolism. No apparent PK interactions were observed between the
      agents. Preliminary activity was observed with PRs in patients with ES-SCLC, high
      grade neuroendocrine tumor, esophageal cancer and NSCLC. CONCLUSIONS: AT-101 with
      cisplatin and etoposide is well tolerated with growth factor support. Anti-tumor
      activity was observed in a variety of cancers including ES-SCLC, supporting
      further investigation with BH-3 mimetics in combination with standard
      chemotherapy for ES-SCLC.

PMID- 23860644
TI  - Chemical probe development versus drug development.
AB  - Phosphatases as a class of proteins have recently attracted significant attention
      from the pharmaceutical industry. As our knowledge of this diverse family of
      proteins has grown, the relationship between phosphatases and human disease has
      clearly been established, with model systems proving much validation for the
      potential of some members of this family to be candidate drug targets. This,
      coupled with the fact that there have been a flood of successful drug development
      efforts over the past 10 years targeting protein kinases, has led some to propose
      that phosphatases as a class of enzymes might be equally as rich a source of drug
      targets as kinases. However to date there remain relatively few molecules
      targeting protein phosphatases in clinical development. This is less a reflection
      of their importance in key processes associated with disease, but rather seems to
      reflect inherent issues with developing drugs for many members of this family.
      This seems especially so for intracellular phosphatases where the development of
      selective, potent cell penetrant molecules with good drug-like properties has
      proven a formidable challenge. This chapter provides a brief outline of the two
      major processes that have resulted in the existing armament of chemical
      modulators of protein phosphatases, namely, chemical probe development and drug
      development. These two processes initially seem to be rather similar and while
      they do overlap, the stated goals of the two approaches at project initiation are
      distinct.

PMID- 23860645
TI  - Phosphatase high-throughput screening assay design and selection.
AB  - Phosphatases are a heterogeneous group of enzymes catalyzing dephosphorylation of
      diverse substrates ranging from small organic molecules to large phosphorylated
      multiprotein complexes. A wide variety of biochemical approaches for measuring
      phosphatase activity exists. Spectrophotometric methods utilizing artificial
      chromogenic, fluorogenic, and luminogenic substrates and taking advantage of the
      optical properties of dephosphorylated products are broadly used by research
      community. Another major assay type is based on quantitation of the second
      product of any phosphatase reactions, inorganic phosphate, using a variety of
      phosphate detection methods. Although, in theory, compatible with any phosphatase
      substrate, these assays often are unable to provide acceptable high-throughput
      screening adaptations of native phosphatase reactions. Conversely, phosphatase
      assays with artificial substrates frequently are incapable to mirror the
      intricacies of substrate binding and catalysis of the native reaction and, as a
      result, unable to deliver biologically relevant phosphatase modulators.
      Utilization of comprehensive phosphatase assay panels, employing honed
      biochemical assays and cell-based model systems, in conjunction with novel
      approaches for screening phosphatases may aid in identification of potent,
      selective, and biologically active phosphatase modulators. 

PMID- 23860646
TI  - Multisystemic functions of alkaline phosphatases.
AB  - Human and mouse alkaline phosphatases (AP) are encoded by a multigene family
      expressed ubiquitously in multiple tissues. Gene knockout (KO) findings have
      helped define some of the precise exocytic functions of individual isozymes in
      bone, teeth, the central nervous system, and in the gut. For instance, deficiency
      in tissue-nonspecific alkaline phosphatase (TNAP) in mice (Alpl (-/-) mice) and
      humans leads to hypophosphatasia (HPP), an inborn error of metabolism
      characterized by epileptic seizures in the most severe cases, caused by abnormal
      metabolism of pyridoxal-5'-phosphate (the predominant form of vitamin B6) and by
      hypomineralization of the skeleton and teeth featuring rickets and early loss of
      teeth in children or osteomalacia and dental problems in adults caused by
      accumulation of inorganic pyrophosphate (PPi). Enzyme replacement therapy with
      mineral-targeting TNAP prevented all the manifestations of HPP in mice, and
      clinical trials with this protein therapeutic are showing promising results in
      rescuing life-threatening HPP in infants. Conversely, TNAP induction in the
      vasculature during generalized arterial calcification of infancy (GACI), type II
      diabetes, obesity, and aging can cause medial vascular calcification. TNAP
      inhibitors, discussed extensively in this book, are in development to prevent
      pathological arterial calcification. The brush border enzyme intestinal alkaline
      phosphatase (IAP) plays an important role in fatty acid (FA) absorption, in
      protecting gut barrier function, and in determining the composition of the gut
      microbiota via its ability to dephosphorylate lipopolysaccharide (LPS). Knockout
      mice (Akp3 (-/-)) deficient in duodenal-specific IAP (dIAP) become obese, and
      develop hyperlipidemia and hepatic steatosis when fed a high-fat diet (HFD).
      These changes are accompanied by upregulation in the jejunal-ileal expression of
      the Akp6 IAP isozyme (global IAP, or gIAP) and concomitant upregulation of
      FAT/CD36, a phosphorylated fatty acid translocase thought to play a role in
      facilitating the transport of long-chain fatty acids into cells. gIAP, but not
      dIAP, is able to modulate the phosphorylation status of FAT/CD36. dIAP, even
      though it is expressed in the duodenum, is shed into the gut lumen and is active
      in LPS dephosphorylation throughout the gut lumen and in the feces. Akp3 (-/-)
      mice display gut dysbiosis and are more prone to dextran sodium sulfate-induced
      colitis than wild-type mice. Of relevance, oral administration of recombinant
      calf IAP prevents the dysbiosis and protects the gut from chronic colitis.
      Analogous to the role of IAP in the gut, TNAP expression in the liver may have a
      proactive role from bacterial endotoxin insult. Finally, more recent studies
      suggest that neuronal death in Alzheimer's disease may also be associated with
      TNAP function on certain brain-specific phosphoproteins. This review recounts the
      established roles of TNAP and IAP and briefly discusses new areas of
      investigation related to multisystemic functions of these isozymes.

PMID- 23860647
TI  - Robotic implementation of assays: tissue-nonspecific alkaline phosphatase (TNAP)
      case study.
AB  - Laboratory automation and robotics have "industrialized" the execution and
      completion of large-scale, enabling high-capacity and high-throughput (100 K-1
      MM/day) screening (HTS) campaigns of large "libraries" of compounds (>200 K-2 MM)
      to complete in a few days or weeks. Critical to the success these HTS campaigns
      is the ability of a competent assay development team to convert a validated
      research-grade laboratory "benchtop" assay suitable for manual or semi-automated
      operations on a few hundreds of compounds into a robust miniaturized (384- or
      1,536-well format), well-engineered, scalable, industrialized assay that can be
      seamlessly implemented on a fully automated, fully integrated robotic screening
      platform for cost-effective screening of hundreds of thousands of compounds.
      Here, we provide a review of the theoretical guiding principles and practical
      considerations necessary to reduce often complex research biology into a "lean
      manufacturing" engineering endeavor comprising adaption, automation, and
      implementation of HTS. Furthermore we provide a detailed example specifically for
      a cell-free in vitro biochemical, enzymatic phosphatase assay for tissue
      nonspecific alkaline phosphatase that illustrates these principles and
      considerations. 

PMID- 23860648
TI  - Inhibitors of tissue-nonspecific alkaline phosphatase (TNAP): from hits to leads.
AB  - The optimization of active hits, commonly derived from high-throughput screening
      campaigns (see Chapters 2 and 4), into promising small-molecule lead compounds is
      one of the fundamental steps in early drug discovery. Directions taken during
      this stage can have important consequences reaching through lead optimization
      into preclinical development and beyond. Considering the ever-increasing costs of
      preclinical as well as clinical development phases (DiMasi et al., J Health Econ
      22:151-185, 2003) the choices made at the early stages of drug discovery can have
      a real impact on the likelihood of the best lead becoming a viable candidate
      (Bleicher et al., Nat Rev Drug Discov 2:369-378, 2003). Thus it is important to
      utilize proven and robust methodologies to turn promising hits into suitable lead
      series with propitious characteristics. Here, we describe such an approach using
      the example of a tissue-nonspecific alkaline phosphatase (see Chapter 3)
      inhibitor developed in our group (Sidique et al., Bioorg Med Chem Lett 19:222
      225, 2009). 

PMID- 23860649
TI  - A method for direct assessment of tissue-nonspecific alkaline phosphatase (TNAP)
      inhibitors in blood samples.
AB  - Tissue nonspecific alkaline phosphatase (TNAP) is one of four human alkaline
      phosphatases (AP), a family of exocytic enzymes that catalyze hydrolysis of
      phospho-monoesters in bone, liver, kidney, and various other tissues.
      Overexpression of TNAP gives rise to excessive bone and soft tissue
      mineralization, including blood vessel calcification. Our prior screening
      campaigns have found several leads against this attractive therapeutic target
      using in vitro assay with a recombinant enzyme; these compounds were further
      optimized using medicinal chemistry approaches. To prioritize compounds for their
      use in animal models, we have designed and developed a biomarker assay for in
      situ detection of TNAP activity within human and mouse blood samples at
      physiological pH. This assay is suitable for screening compounds in 1,536-well
      plates using blood plasma from different mammalian species. The user may choose
      from two different substrates based on the need for greater assay simplicity or
      sensitivity. 

PMID- 23860650
TI  - Isolation and characteristics of matrix vesicles.
AB  - Mineralizing matrix vesicles (MVs) are extracellular organelles produced by
      chondrocytes, osteoblasts, and odontoblasts under physiological conditions and by
      vascular smooth muscle cells under pathological conditions. MVs are involved in
      the early stage of mineralization allowing calcium and phosphate to accumulate,
      and therefore providing an optimal environment facilitating hydroxyapatite
      formation. Here, we describe the isolation of MVs from osteoblasts and
      chondrocytes and present their main characteristics. 

PMID- 23860651
TI  - The use of tissue-nonspecific alkaline phosphatase (TNAP) and PHOSPHO1 inhibitors
      to affect mineralization by cultured cells.
AB  - Here, we describe methods to evaluate the ability of small molecules inhibitors
      of TNAP and PHOSPHO1 in preventing mineralization of primary cultures of murine
      vascular smooth muscle cells. The procedures are also applicable to primary
      cultures of calvarial osteoblasts. These cell-based assays are used to complement
      kinetic testing during structure-activity relationship studies aimed at improving
      scaffolds in the generation of pharmaceuticals for the treatment for medial
      vascular calcification. 

PMID- 23860652
TI  - Modulators of intestinal alkaline phosphatase.
AB  - Small molecule modulators of phosphatases can lead to clinically useful drugs and
      serve as invaluable tools to study functional roles of various phosphatases in
      vivo. Here, we describe lead discovery strategies for identification of
      inhibitors and activators of intestinal alkaline phosphatases. To identify
      isozyme-selective inhibitors and activators of the human and mouse intestinal
      alkaline phosphatases, ultrahigh throughput chemiluminescent assays, utilizing
      CDP-Star as a substrate, were developed for murine intestinal alkaline
      phosphatase (mIAP), human intestinal alkaline phosphatase (hIAP), human placental
      alkaline phosphatase (PLAP), and human tissue-nonspecific alkaline phosphatase
      (TNAP) isozymes. Using these 1,536-well assays, concurrent HTS screens of the
      MLSMR library of 323,000 compounds were conducted for human and mouse IAP
      isozymes monitoring both inhibition and activation. This parallel screening
      approach led to identification of a novel inhibitory scaffold selective for
      murine intestinal alkaline phosphatase. SAR efforts based on parallel testing of
      analogs against different AP isozymes generated a potent inhibitor of the murine
      IAP with IC50 of 540 nM, at least 65-fold selectivity against human TNAP, and
      >185 selectivity against human PLAP. 

PMID- 23860653
TI  - New activity assays for ENPP1 with physiological substrates ATP and ADP.
AB  - Existing assays monitoring ENPP1 activity are either not physiologically relevant
      or not suitable for high-throughput screening (HTS). Here, we describe the
      development and implementation of two new ENPP1 activity assays that address
      these drawbacks. These assays employ physiological substrates of ENPP1, ATP and
      ADP. They rely on detection of inorganic phosphate using a special modification
      of the malachite green-molybdate colorimetric procedure that ensures stability of
      acid-labile compounds, such as the ones containing phosphodiester bonds. The
      pyrophosphate generated in ENPP1 reaction is converted to inorganic phosphate in
      the presence of inorganic phosphatase; whereas, omission of this coupling enzyme
      enables detection of the inorganic phosphate generated by ENPP1. These new ENPP1
      assays were miniaturized into high-density microplate formats. With minimal
      requirement for ENPP1 enzyme, low micromolar phosphate detection sensitivity, and
      simple protocol involving three to four simple liquid handling steps, these
      robust assays are suitable for HTS. 

PMID- 23860654
TI  - Structure of Acid phosphatases.
AB  - Acid phosphatases are enzymes that have been studied extensively due to the fact
      that their dysregulation is associated with pathophysiological conditions. This
      characteristic has been exploited for the development of diagnostic and
      therapeutic methods. As an example, prostatic acid phosphatase was the first
      marker for metastatic prostate cancer diagnosis and the dysregulation of tartrate
      resistant acid phosphatase is associated with abnormal bone resorption linked to
      osteoporosis. The pioneering crystallization studies on prostatic acid
      phosphatase and mammalian tartrate-resistant acid phosphatase conformed
      significant milestones towards the elucidation of the mechanisms followed by
      these enzymes (Schneider et al., EMBO J 12:2609-2615, 1993). Acid phosphatases
      are also found in nonmammalian species such as bacteria, fungi, parasites, and
      plants, and most of them share structural similarities with mammalian acid
      phosphatase enzymes. Acid phosphatase (EC 3.1.3.2) enzymes catalyze the
      hydrolysis of phosphate monoesters following the general equation. Phosphate
      monoester + H2O -->/<-- alcohol + phosphate. The general classification "acid
      phosphatase" relies only on the optimum acidic pH for the enzymatic activity in
      assay conditions using non-physiological substrates. These enzymes accept a wide
      range of substrates in vitro, ranging from small organic molecules to
      phosphoproteins, constituting a heterogeneous group of enzymes from the
      structural point of view. These structural differences account for the divergence
      in cofactor dependences and behavior against substrates, inhibitors, and
      activators. In this group only the tartrate-resistant acid phosphatase is a
      metallo-enzyme whereas the other members do not require metal-ion binding for
      their catalytic activity. In addition, tartrate-resistant acid phosphatase and
      erythrocytic acid phosphatase are not inhibited by L-(+)-tartrate ion while the
      prostatic acid phosphatase is tartrate-sensitive. This is an important difference
      that can be exploited in in vitro assays to differentiate between different kinds
      of phosphatase activity. The search for more sensitive and specific methods of
      detection in clinical laboratory applications led to the development of
      radioimmunoassays (RIA) for determination of prostatic acid phosphatase in serum.
      These methods permit the direct quantification of the enzyme regardless of its
      activity status. Therefore, an independent structural classification exists that
      helps to group these enzymes according to their structural features and
      mechanisms. Based on this we can distinguish the histidine acid phosphatases (Van
      Etten, Ann N Y Acad Sci 390:27-51, 1982), the low molecular weight protein
      tyrosine acid phosphatases and the metal-ion dependent phosphatases. A note of
      caution is worthwhile mentioning here. The nomenclature of acid phosphatases has
      not been particularly easy for those new to the subject. Unfortunately, the
      acronym PAP is very common in the literature about purple acid phosphatases and
      prostatic acid phosphatase. In addition, LPAP is the acronym chosen to refer to
      the lysophosphatidic acid phosphatase which is a different enzyme. It is
      important to bear in mind this distinction while reviewing the literature to
      avoid confusion.

PMID- 23860655
TI  - Purification of prostatic acid phosphatase (PAP) for structural and functional
      studies.
AB  - High-scale purification methods are required for several protein studies such as
      crystallography, mass spectrometry, circular dichroism, and function. Here we
      describe a purification method for PAP based on anion exchange, L-(+)-tartrate
      affinity, and gel filtration chromatographies. Acid phosphatase activity and
      protein concentration were measured for each purification step, and to collect
      the fractions with the highest acid phosphatase activity the p-nitrophenyl
      phosphate method was used. The purified protein obtained by the procedure
      described here was used for the determination of the first reported three
      dimensional structure of prostatic acid phosphatase. 

PMID- 23860656
TI  - Protein tyrosine phosphatases: structure, function, and implication in human
      disease.
AB  - Protein tyrosine phosphorylation is a key regulatory mechanism in eukaryotic cell
      physiology. Aberrant expression or function of protein tyrosine kinases and
      protein tyrosine phosphatases can lead to serious human diseases, including
      cancer, diabetes, as well as cardiovascular, infectious, autoimmune, and
      neuropsychiatric disorders. Here, we give an overview of the protein tyrosine
      phosphatase superfamily with its over 100 members in humans. We review their
      structure, function, and implications in human diseases, and discuss their
      potential as novel drug targets, as well as current challenges and possible
      solutions to developing therapeutics based on these enzymes. 

PMID- 23860657
TI  - High-throughput screening for protein tyrosine phosphatase activity modulators.
AB  - Reversible phosphorylation of proteins, principally on serine, threonine, or
      tyrosine residues, is central to the regulation of most aspects of eukaryotic
      cell function. Dysregulation of protein kinases and protein phosphatases is
      linked to numerous human diseases. Consequently, many efforts have been made to
      target these enzymes with small molecules in order to develop new therapeutic
      agents. While protein kinase inhibitors have been successfully brought to the
      market, the development of specific protein phosphatase inhibitors is still in
      its infancy. The largest and most diverse protein phosphatase superfamily in
      humans is comprised by the protein tyrosine phosphatases, a group of over 100
      enzymes. Here, we describe high-throughput screening methods to search for
      protein tyrosine phosphatase activity modulators. We illustrate the
      implementation of relatively simple phosphatase assays, using generic absorbance-
      or fluorescence-based substrates, in 384- or 1536-well microtiter plates. We
      discuss steps to optimize HTS assay quality and performance, and describe several
      PTP screening methods on the basis of previously performed successful HTS
      campaigns. Finally, we discuss how to confirm, follow up, and prioritize hit
      compounds, and point out a number of common pitfalls that are encountered in this
      process. 

PMID- 23860658
TI  - Evaluating effects of tyrosine phosphatase inhibitors on T cell receptor
      signaling.
AB  - The importance of tyrosine phosphorylation in normal cell physiology is well
      established, highlighted by the many human diseases that stem from abnormalities
      in protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) function.
      Contrary to earlier assumptions, it is now clear that both PTKs and PTPs are
      highly specific, non-redundant, and tightly regulated enzymes. Hematopoietic
      cells express particularly high numbers of PTKs and PTPs, and aberrant function
      of these proteins have been linked to many hematopoietic disorders. While PTK
      inhibitors are among FDA approved drugs for the treatment of leukemia and other
      cancers, efforts to develop therapeutics that target specific PTPs are still in
      its infancy. Here, we describe methods on how to evaluate effects of PTP
      inhibitors on T cell receptor signaling. Moreover, we provide a comprehensive
      strategy for compound prioritization, applicable to any drug discovery project
      involving T cells. We present a testing funnel that starts with relatively high
      throughput luciferase reporter assays, followed by immunoblot, calcium flux, flow
      cytometry, and proliferation assays, continues with cytokine bead arrays, and
      finishes with specificity assays that involve RNA interference. We provide
      protocols for experiments in the Jurkat T cell line, but more importantly give
      detailed instructions, paired with numerous tips, on how to prepare and work with
      primary human T cells. 

PMID- 23860659
TI  - Interactor-guided dephosphorylation by protein phosphatase-1.
AB  - Protein phosphatase-1 (PP1) is an essential enzyme for every eukaryotic cell and
      catalyzes more than half of all protein dephosphorylations at serine and
      threonine residues. The free catalytic subunit of PP1 shows little substrate
      selectivity but is tightly regulated in vivo by a large variety of structurally
      unrelated PP1-interacting proteins (PIPs). PIPs form highly specific dimeric or
      trimeric PP1 holoenzymes by acting as substrates, inhibitors, and/or substrate
      specifiers. The surface of PP1 contains many binding sites for short PP1-docking
      motifs that are combined by PIPs to create a PP1-binding code that is universal,
      specific, degenerate, nonexclusive, and dynamic. These properties of the PP1
      binding code can be used for the rational design of small molecules that disrupt
      subsets of PP1 holoenzymes and have a therapeutic potential. 

PMID- 23860660
TI  - Structure, regulation, and pharmacological modulation of PP2A phosphatases.
AB  - Protein phosphatases of the type 2A family (PP2A) represent a major fraction of
      cellular Ser/Thr phosphatase activity in any given human tissue. In this review,
      we describe how the holoenzymic nature of PP2A and the existence of several
      distinct PP2A composing subunits allow for the generation of multiple
      structurally and functionally different PP2A complexes, explaining why PP2A is
      involved in the regulation of so many diverse cell biological and physiological
      processes. Moreover, in human disease, most notably in several cancers and
      Alzheimer's Disease, PP2A expression and/or activity have been found
      significantly decreased, underscoring its important functions as a major tumor
      suppressor and tau phosphatase. Hence, several recent preclinical studies have
      demonstrated that pharmacological restoration of PP2A activity, as well as
      pharmacological PP2A inhibition, under certain conditions, may be of significant
      future therapeutic value. 

PMID- 23860661
TI  - Toll-like receptor 2 controls acute immune complex-driven arthritis in mice by
      regulating the inhibitory Fcgamma receptor IIB.
AB  - OBJECTIVE: Previous studies have demonstrated a protective role of Toll-like
      receptor 2 (TLR-2) and a proinflammatory function of TLR-4 during chronic T cell
      driven arthritis. The involvement of TLRs in T cell-independent arthritic
      processes, however, remains unclear. This study was undertaken to determine the
      functional significance of TLR-2 and TLR-4 in T cell-independent immune complex
      driven arthritis. METHODS: Serum-transfer arthritis was induced in wild-type and
      TLR-deficient mice by intraperitoneal injections of arthritogenic K/BxN mouse
      serum. Arthritis was assessed macroscopically and by histologic analysis. The
      influence of TLR-2 on macrophage cytokine profile, Fcgamma receptor (FcgammaR)
      expression, and response to immune complexes was determined. RESULTS: While TLR
      4, unexpectedly, did not play any significant role, TLR-2 deficiency accelerated
      the onset and markedly increased the severity of acute immune complex-driven
      arthritis in mice. TLR-2 deficiency resulted in a substantial increase in joint
      inflammation, bone erosion, and cartilage pathology, indicating a protective
      function of TLR-2 in passive FcgammaR-driven disease. Ex vivo study of the
      macrophage inflammatory phenotype revealed increased production of tumor necrosis
      factor alpha (TNFalpha) and interleukin-6 (IL-6) despite similar levels of IL-10,
      along with a significant increase in FcgammaR-specific response, in TLR-2-/-
      mouse macrophages early in the disease. Although distinct FcgammaR messenger RNA
      expression was not affected, cell surface protein expression of the inhibitory
      FcgammaRIIB in TLR-2-/- naive primary macrophages was specifically diminished,
      resulting in a higher proinflammatory response. Accordingly, TLR-2 stimulation
      specifically up-regulated FcgammaRIIB, but not the activating FcgammaR, on
      macrophages. CONCLUSION: TLR-2 regulates acute immune complex-driven arthritis by
      controlling macrophage FcgammaR response. Our findings indicate that the
      protective role of TLR-2 is extended beyond its previously described role in
      promoting Treg cells during T cell-mediated arthritis.

PMID- 23860663
TI  - Enabling light-driven water oxidation via a low-energy RuIV=O intermediate.
AB  - The discovery of catalysts capable of driving water oxidation at relatively low
      overpotential is a key challenge for efficient photoinduced water oxidation. The
      mononuclear Ru(II) polypyridyl complex (1) [Ru(NPM)(H2O)(pic)2](2+) (NPM = 4-tert
      butyl-2,6-di-(1',8'-naphthyrid-2'-yl)-pyridine, pic = 4-picoline) has been
      examined as a catalyst for visible-light-driven water oxidation in a three
      component homogeneous system containing [Ru(bpy)3](2+) as a photosensitizer,
      persulfate as a sacrificial electron acceptor and catalyst 1. In contrast to the
      well-established water oxidation mechanism via the nucleophilic attack of a water
      molecule on the high-energy [Ru(V)=O](3+) species, a lower-energy "direct
      pathway" for O-O bond formation via a [Ru(IV)=O](2+) intermediate was proposed
      for the first time for the catalyst 1 (Polyansky et al., J. Am. Chem. Soc., 2011,
      133, 14649). In this report we successfully demonstrate that this unique proton
      coupled low-energy pathway actually takes place with the use of a mild oxidant
      such as the photogenerated [Ru(bpy)3](3+) (1.26 V vs. NHE) to drive water
      oxidation. The overall quantum yield of 9%, TOF of 0.12 s(-1) and TON of 103
      (limited solely by a drop in pH) were found for photochemical water oxidation
      with 1 using [Ru(bpy)3](2+) as a photosensitizer and [S2O8](2-) as a sacrificial
      electron acceptor. These values render catalyst 1 as one of the most active
      mononuclear ruthenium-based catalysts for light-driven water oxidation in a
      homogeneous system. The utilization of a pH-dependent pathway for water oxidation
      is a new and promising direction as a low-energy pathway. Furthermore, the
      detailed analysis of individual photochemical steps leading to O2 evolution
      provides benchmarks for future mechanistic studies of photo-induced water
      oxidation catalysis.

PMID- 23860664
TI  - Infarct volume predicts delayed recovery in patients with subarachnoid hemorrhage
      and severe neurological deficits.
AB  - BACKGROUND: Recovery is common after subarachnoid hemorrhage (SAH), even in
      patients who are severely disabled at hospital discharge. Little is known about
      predictors of late recovery in such patients, even though such knowledge may
      influence treatment decisions. We hypothesized that cerebral infarction volume
      would be associated with 3 months outcomes in patients who are severely disabled
      at 14 days. METHODS: We prospectively identified consecutive aneurysmal SAH
      patients, documented the development of cerebral infarction, and ascertained the
      modified Rankin Scale (mRS) at 14 days and 3 months. We included patients with
      mRS 4 or 5 and NIH Stroke Scale (NIHSS) at least 8 on hospital day 14 (i.e.,
      severe neurologic impairment) and calculated infarct volume in a semi-automated
      fashion using CT imaging. We explored outcome determinants with ordinal
      regression. RESULTS: At 14 days, 66 patients were severely disabled, 65 (98.5 %)
      of whom had mRS of 5; the median NIHSS was 21 [14-24]. At 3 months, 20 (32.8 %)
      of the 61 patients with known outcomes were independent. Larger infarction
      volumes were associated with death (20.4 vs. 0.85 mL, P = 0.02). In ordinal
      regression, increased infarct volume was associated with the worse mRS after
      correction for WFNS grade, age, and withdrawal of life support (OR 1.01 per mL of
      infarct, 95 % CI 1.01-1.03, P = 0.01). CONCLUSIONS: After SAH, even with severe
      neurological injury at 14 days, good recovery is frequent and is associated with
      lower infarction volume. These data may help clinicians inform surrogate decision
      makers as they plan the future care of such severely disabled patients.

PMID- 23860666
TI  - QTc-prolongation in posterior circulation stroke.
AB  - BACKGROUND AND PURPOSE: To evaluate the relationship between infarct location and
      QTc-prolongation in patients with posterior circulation strokes. METHODS:
      Admission electrocardiograms (ECG) of 131 patients among a prospective sample of
      407 consecutive adult patients in the New England Medical Center Posterior
      Circulation Registry were retrospectively analyzed. The QT interval (ms) was
      measured and corrected using Bazett's formula (QTcBazett) as well as linear
      regression functions (QTcLinear). QTcBazett > 440 ms and QTcLinear >= 450 ms for
      men (>=460 ms for women) were considered prolonged. Multivariable linear and
      logistic regression analyses were used to identify independent predictors of the
      QTc. RESULTS: Overall, 34% of patients had a prolonged QTcBazett and 7% had a
      prolonged QTcLinear noted on the admission ECG. There was a significant
      association between temporal lobe infarction and QTcBazett and QTcLinear (p <
      0.001 for both) in multivariable linear regression analyses adjusting for
      demographics, ECG parameters, and preadmission medication use. In multivariable
      logistic regression analysis, temporal lobe infarction emerged as an independent
      predictor of prolonged QTcBazett (p = 0.009) and QTcLinear (p = 0.008),
      respectively. Sensitivity analyses excluding patients with transient ischemic
      attack yielded similar results. Exploratory analyses indicated that patients with
      temporal lobe infarction had worse functional 30-day outcomes in multivariable
      logistic regression (p = 0.022). However, there was no significant association
      between QTc and 30-day functional outcome. CONCLUSIONS: QTc-prolongation is
      common after posterior circulation stroke and associated with temporal lobe
      infarction. Prospective studies are needed to confirm these preliminary findings
      and to examine potential long-term consequences.

PMID- 23860665
TI  - Unexpected recovery of function after severe traumatic brain injury: the limits
      of early neuroimaging-based outcome prediction.
AB  - BACKGROUND: Prognostication in the early stage of traumatic coma is a common
      challenge in the neuro-intensive care unit. We report the unexpected recovery of
      functional milestones (i.e., consciousness, communication, and community
      reintegration) in a 19-year-old man who sustained a severe traumatic brain
      injury. The early magnetic resonance imaging (MRI) findings, at the time,
      suggested a poor prognosis. METHODS: During the first year of the patient's
      recovery, MRI with diffusion tensor imaging and T2*-weighted imaging was
      performed on day 8 (coma), day 44 (minimally conscious state), day 198 (post
      traumatic confusional state), and day 366 (community reintegration). Mean
      apparent diffusion coefficient (ADC) and fractional anisotropy values in the
      corpus callosum, cerebral hemispheric white matter, and thalamus were compared
      with clinical assessments using the Disability Rating Scale (DRS). RESULTS:
      Extensive diffusion restriction in the corpus callosum and bihemispheric white
      matter was observed on day 8, with ADC values in a range typically associated
      with neurotoxic injury (230-400 * 10(-6 )mm(2)/s). T2*-weighted MRI revealed
      widespread hemorrhagic axonal injury in the cerebral hemispheres, corpus
      callosum, and brainstem. Despite the presence of severe axonal injury on early
      MRI, the patient regained the ability to communicate and perform activities of
      daily living independently at 1 year post-injury (DRS = 8). CONCLUSIONS: MRI data
      should be interpreted with caution when prognosticating for patients in traumatic
      coma. Recovery of consciousness and community reintegration are possible even
      when extensive traumatic axonal injury is demonstrated by early MRI.

PMID- 23860667
TI  - Serum S100B protein could help to detect cerebral complications associated with
      extracorporeal membrane oxygenation (ECMO).
AB  - BACKGROUND: To investigate if serum S100B protein levels could early detect
      cerebral complications under treatment extracorporeal membrane oxygenation
      (ECMO). METHODS: Serum S100B levels were measured over 5 days in 32 patients with
      cardiogenic and septic shock, including 15 patients who treated by ECMO and 17
      who did not. Cerebral complications included hemorrhage, stroke, encephalopathy
      with myoclonus, and brain death. Delirium was identified by the positive
      Confusion Assessment Method in the ICU. RESULTS: S100B levels were elevated in
      24/32 patients (75 %) at ICU admission. Five patients developed cerebral
      complications (2 hemorrhages with 1 brain death, 1 encephalopathy with myoclonus
      in the ECMO group and 2 strokes in the non-ECMO group). At day 5, S100B levels
      were higher in the 5 patients with cerebral complications than in the 27 without
      cerebral complications, regardless of ECMO (0.426 [0.421, 0.652] vs. 0.102
      [0.085, 0.135] MUg/L, p = 0.011). S100B levels were also more elevated in 3
      patients with than in 12 without cerebral complications associated with ECMO
      (0.799 [0.325, 0.965] vs. 0.102 [0.09, 0.607] MUg/L, p = 0.033). S100B levels
      were not associated with delirium after sedation withdrawal. CONCLUSIONS:
      Measurement serum S100B could be useful to detect cerebral complications in
      deeply sedated patients associated with ECMO but not for monitoring delirium
      after sedation withdrawal.

PMID- 23860668
TI  - Bedside diagnosis of mitochondrial dysfunction after malignant middle cerebral
      artery infarction.
AB  - BACKGROUND: The study explores whether the cerebral biochemical pattern in
      patients treated with hemicraniectomy after large middle cerebral artery infarcts
      reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. METHODS: The
      study includes 44 patients treated with decompressive hemicraniectomy (DCH) due
      to malignant middle cerebral artery infarctions. Chemical variables related to
      energy metabolism obtained by microdialysis were analyzed in the infarcted tissue
      and in the contralateral hemisphere from the time of DCH until 96 h after DCH.
      RESULTS: Reperfusion of the infarcted tissue was documented in a previous report.
      Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in
      the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12
      to 96 h after DCH the pyruvate level was significantly higher in the infarcted
      tissue than in the non-infarcted hemisphere (p < 0.05). CONCLUSION: After a
      prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows
      signs of protracted mitochondrial dysfunction, characterized by a marked increase
      in cerebral lactate level with a normal or increased cerebral pyruvate level
      resulting in an increased LP-ratio. This biochemical pattern contrasts to
      cerebral ischemia, which is characterized by a marked decrease in cerebral
      pyruvate. The study supports the hypothesis that it is possible to diagnose
      cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by
      microdialysis and bed-side biochemical analysis.

PMID- 23860669
TI  - Branches and arterial supply of the recurrent artery of Heubner.
AB  - The aim of this study was to describe the branches and arterial supply of the
      recurrent artery of Heubner (RAH) in order to provide detailed information to
      neurosurgeons operating in this area of the brain. A total of 70 human brains (39
      male and 31 female) obtained from cadavers (aged 31-75 years) during routine
      autopsies were examined; brains from individuals who died due to neurological
      disorders were not included in the study. Immediately after dissection the
      arteries were perfused with acrylic paint emulsion through the circle of Willis
      or electively through the RAH. Brains were fixed in a 10 % solution of
      formaldehyde and sectioned; the sections were analyzed under a stereoscopic light
      microscope (magnification 2-40*). The RAH was present in 138 hemispheres with a
      mean of 1.99 per hemisphere. Mean RAH length was 25.2 mm and the mean diameter,
      in its place of origin, was 1 mm. Between two and 30 (mean 9.4) branches
      originated from the stem of the RAH. Each branch then divided into 2-40 smaller
      branches (mean 19). Primary branches were divided and named in accordance with
      their course and arterial supply. Primary RAH branches include the anterior
      perforating substance, sylvian fissure, olfactory, frontal, hypothalamic, optic
      tract and connecting branches. Left and right hemispheres were asymmetrically
      supplied by RAH branches, but none of these discrepancies were of statistical
      significance. 

PMID- 23860670
TI  - [Calyceal stones].
AB  - The natural course of untreated, asymptomatic calyceal calculi has not yet been
      clearly defined regarding disease progression and risk of surgical interventions.
      The decision for an active treatment of calyceal calculi is based on stone
      composition, stone size and symptoms. Extracorporeal shockwave lithotripsy (ESWL)
      has a low complication rate and is recommended by the current guidelines of the
      German (DGU) and European (EAU) Associations of Urology as a first-line therapy
      for the treatment of calyceal stones <2 cm in diameter. However, immediate
      removal of stones is not achieved with ESWL. The primary stone-free rates (SFR)
      after ESWL depend on stone location and stone composition and can show remarkable
      differences. Minimally invasive procedures, such as percutaneous
      nephrolitholapaxy and ureteroscopy are alternatives for the treatment of calyceal
      stones which have low morbidity and high primary SFR when performed in centres of
      excellence.

PMID- 23860671
TI  - Understanding osteoporosis and fractures: an introduction to the use of
      qualitative research.
AB  - BACKGROUND: Qualitative research has been recognized in recent years as a field
      of inquiry used to understand people's beliefs, attitudes, behaviors, culture or
      lifestyle. While quantitative results are challenging to apply in everyday
      practice, the qualitative paradigm can be useful to fill in a research context
      that is poorly understood or ill-defined. It can provide an in-depth study of
      interactions, a way to incorporate context, and a means to hear the voices of
      participants. Understanding experiences, motivation, and beliefs can have a
      profound effect on the interpretation of quantitative research and generating
      hypotheses. In this paper, we will review different qualitative approaches that
      healthcare providers and researchers may find useful to implement in future study
      designs, specifically in the context of osteoporosis and fracture. METHODS: We
      will provide insight into the qualitative paradigm gained from the osteoporosis
      literature on fractures using examples from the database Scopus. Five prominent
      qualitative techniques (narratives, phenomenology, grounded theory, ethnography,
      and case study) can be used to generate meanings of the social and clinical
      world. DISCUSSION AND CONCLUSION: We have highlighted how these strategies are
      implemented in qualitative research on osteoporosis and fractures and are
      anchored to specific methodological practices. We focus on studies that explore
      patient psychosocial experiences of diagnosis and treatment, cultural boundaries,
      and interprofessional communication. After reviewing the research, we believe
      that action research, that is not frequently used, could also effectively be used
      by many professions to improve programs and policies affecting those dealing with
      osteoporosis issues.

PMID- 23860672
TI  - Does laminoplasty really improve neurological status in patients with cervical
      spinal cord injury without bone and disc injury? A prospective study about
      neurological recovery and early complications.
AB  - PURPOSE: Cervical spinal cord injury without bone and disc injury in patients
      with spinal cord compression is a fairly common problem in Japan. Because elderly
      Japanese population tend to have cervical spinal canal stenosis. However, there
      has been no consensus in the treatment of these patients. We conducted a
      prospective study to evaluate treatment outcomes and complications of these
      patients. METHODS: Twenty-five patients had been enrolled in this study. Patients
      who had paralysis of ASIA impairment scale (AIS) A, B or C were included. With
      each new patient, we alternated whether he/she received surgical treatment (group
      S) or conservative treatment (group C). Eleven patients were assigned to each
      group. We compared the two groups' courses of treatment and complications by
      evaluating their neurological symptoms using the AIS and ASIA motor score (MS)
      documenting them at the time of injury and 3 months later. RESULTS: The majority
      of clinical paralysis was found at the C3/4 level for both the groups. According
      to complications, there were seven urinary tract infections and four pneumonias
      in group S and one urinary tract infection and three pneumonias in group C. Both
      groups had an average MS of 42 at the time of injury. Three months later, the
      average MSs were 59 points in group S and 65 points in group C. CONCLUSIONS: In
      the present study, we found no significant difference in paralysis improvement
      between surgical and conservative treatment, although we observed a higher
      frequency of complications with surgery.

PMID- 23860673
TI  - Surgical treatment of thoracic spinal tuberculosis with adjacent segments lesion
      via one-stage transpedicular debridement, posterior instrumentation and combined
      interbody and posterior fusion, a clinical study.
AB  - PURPOSE: To investigate the clinical efficacy and feasibility of one-stage
      surgical treatment for thoracic spinal tuberculosis with adjacent segments lesion
      by internal fixation, transpedicular debridement, and combined interbody and
      posterior fusion via a posterior-only approach. MATERIALS AND METHODS: Twenty-one
      patients (thirteen males, eight females) with thoracic tuberculosis whose lesions
      were confined to two adjacent segments were studied retrospectively. All patients
      were treated with one-stage surgical treatment by internal fixation,
      transpedicular debridement, and combined interbody and posterior fusion via a
      posterior-only approach. The American Spinal Injury Association (ASIA) impairment
      scale was used to assess neurological function. Thoracic Cobb angle was used to
      assess thoracic kyphosis. Operating time, blood loss, complications, neurological
      function, deformity correction and interbody fusion were investigated. RESULTS:
      Average mean operating time was 231.4 +/- 31.9 min, and evaluated blood loss
      during operation was 880.2 +/- 112.7 ml. All patients were followed up for 22-41
      months postoperatively (average 29.8 +/- 5.4 months). All patients had
      significant postoperative improvement in ASIA classification scores. The thoracic
      kyphotic angles were significantly decreased to 9 degrees -25 degrees 
      postoperatively (average 16.7 degrees  +/- 4.4 degrees ), and at final follow-up
      were 10 degrees -27 degrees (average 17.7 degrees  +/- 4.4 degrees ). No severe
      complications or spinal cord injury occurred. The erythrocyte sedimentation rate
      recovered to normal within 3 months postoperatively in all patients. All patients
      got bony fusion within 6-9 months after surgery. CONCLUSIONS: One-stage
      transpedicular debridement, posterior instrumentation and combined interbody and
      posterior fusion via a posterior-only approach can be an effective and feasible
      treatment method for thoracic spinal tuberculosis.

PMID- 23860674
TI  - Early conversion to below-elbow cast for non-reduced diaphyseal both-bone forearm
      fractures in children is safe: preliminary results of a multicentre randomised
      controlled trial.
AB  - INTRODUCTION: This multicentre randomised controlled trial was designed to
      explore whether 6 weeks above-elbow cast (AEC) or 3 weeks AEC followed by 3 weeks
      below-elbow cast (BEC) cause similar limitation of pronation and supination in
      non-reduced diaphyseal both-bone forearm fractures in children. MATERIALS AND
      METHODS: Children were randomly allocated to 6 weeks AEC or to 3 weeks AEC
      followed by 3 weeks BEC. The primary outcome was limitation of pronation and
      supination after 6 months. The secondary outcomes were re-displacement of the
      fracture, complication rate, limitation of flexion and extension of wrist and
      elbow, cast comfort, cosmetics, complaints in daily life and assessment of
      radiographs. RESULTS: A group of 23 children was treated with 6 weeks AEC and 24
      children with 3 weeks AEC and 3 weeks BEC. The follow-up rate was 98 % with a
      mean follow-up of 7.0 months. The mean limitation of pronation and supination was
      23.3 +/- 22.0 for children treated with AEC and 18.0 +/- 16.9 for children
      treated with AEC and BEC. The other study outcomes were similar in both groups.
      CONCLUSIONS: Early conversion to BEC is safe in the treatment of non-reduced
      diaphyseal both-bone forearm fractures in children. LEVEL OF EVIDENCE:
      Multicentre randomised controlled trial, Level II.

PMID- 23860675
TI  - The assessment of neutrophil CD64 count as an early warning marker of joint
      replacement infection.
AB  - 120,000 hip and knee replacements are performed each year in the UK and more than
      1 % of these require revision surgery due to infection. Current diagnostic tests
      used to diagnose infection of joint replacements, including the current gold
      standard C-reactive protein, which offers poor specificity when diagnosing
      infection in the post-operative period. In the post-operative period these tests
      are unable to differentiate between physiological inflammation and infection of
      the replacement. Early treatment through antibiotic and washout therapy is
      essential to eradicate infection, saving the patient and the NHS the stress of
      revision surgery, which offers a much poorer prognosis than the original
      operative procedure. Thus, a superior marker is required and CD64 has been
      proposed to fulfil the necessary requirements of an effective marker. Data from
      several studies utilising a flow cytometer support the view that CD64 is firstly,
      a good marker of systemic infection and secondly, when studied in conjunction
      with musculoskeletal infections alone, is a sensitive and specific marker of this
      type of infection. However, meta-analysis of studies in this field concludes that
      more highly powered studies are needed before definite conclusions can be drawn.
      Despite this, the studies do portray a strong case for CD64 being the future of
      diagnosis of post-operative infection. 

PMID- 23860676
TI  - Current evidence in gastrointestinal surgery: natural orifice translumenal
      endoscopic surgery (NOTES).
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is a
      technique that uses transvisceral access to perform surgical procedures entirely
      through a natural orifice. Despite the increasing awareness of NOTES, there
      remain obstacles to its technical feasibility and widespread acceptance.
      Furthermore, with the paucity of high-level supporting evidence, NOTES currently
      remains an experimental technique. OBJECTIVE: This article reviews the goals,
      applications, technical and practical challenges, and future direction of NOTES
      in gastrointestinal surgery.

PMID- 23860677
TI  - Sphincter of Oddi dysfunction: how is it diagnosed? How is it classified? How do
      we treat it medically, endoscopically, and surgically?

PMID- 23860678
TI  - [Is an age-adjusted D-dimer cut-off value more accurate?--Age-adjusted D-dimer
      cut-off values clearly increase specificity].

PMID- 23860679
TI  - [Correlation of patients age on length of stay and admission rate in a German
      emergency department].
AB  - BACKGROUND: This study aimed to examine correlations between patient age, length
      of-stay (LOS) in the emergency department (ED), admission rate for various
      medical disciplines and probabilities of admission in a German interdisciplinary
      ED. PATIENTS AND METHODS: In a retrospective cohort analysis, 7937 patients of
      the ED were evaluated for age, gender, ED-LOS and admission rate. Rank
      correlation coefficients were calculated in order to analyze the influence of
      patient age for each discipline. Statistical tests were performed to evaluate
      explorative hypotheses on specific discipline influence of patient age. RESULTS:
      Patients age significantly differed between the disciplines. There was a strong
      correlation between patient age and LOS for trauma surgery, visceral surgery and
      ophthalmology. The correlation between patient age and admission rate was highest
      in patients with problems regarding internal medicine, trauma surgery and
      neurology. CONCLUSION: There is a correlation between patients age, LOS and
      admission rate in the ED.

PMID- 23860680
TI  - [Arthropathia ochronotica: a rare cause of early joint degeneration].
AB  - HISTORY AND ADMISSION FINDINGS: A 70-year-old deaf-mute women suffered from
      progressive chronic pain of the right hip joint caused by destructive
      osteoarthritis of the hip. INVESTIGATIONS: In addition to painfully restricted
      range of motion of the right hip joint the clinical examination showed a bluish
      black pigmentation of the ear-cartilage and the sclera. TREATMENT AND COURSE: A
      total endoprosthetic replacement of the right hip joint was performed. During
      surgery, blackening of the hip joint capsule and cartilage was found.
      Histological, the diagnosis of an ochronosis was confirmed. Discoloration after
      exposure of urine to air supported the diagnosis. Based on extensive internal
      medical examination relevant cardiac changes were excluded. CONCLUSION:
      Ochronosis (arthropathia ochronotica) is a rare entity which can be identified by
      a visual diagnosis. Early diagnosis can provide crucial information for the
      prognosis. Additionally, an interdisciplinary treatment concept should be
      established because of the early onset of degenerative changes at the skeletal
      system and pathological changes at internal organs. With suspicion on an
      ochronosis extended internal examinations are recommended in order to avoid
      complications.

PMID- 23860681
TI  - [56-year-old patient with angina pectoris and progressive shortness of breath].

PMID- 23860682
TI  - [Glomerulonephritis].
AB  - Glomerulonephritides represent a heterogenous group of diseases with different
      pathophysiology. A definitive diagnosis requires a renal biopsy. The
      differentiation between a primary or secondary glomerulonephritis is of major
      clinical relevance, because most secondary forms resolve once the primary cause
      is treated properly. Assessing the individual prognosis of a patient is of
      central importance in choosing the best therapeutic regimen. By optimizing the so
      called supportive therapy with the control of blood pressure, reduction of
      proteinuria, cessation of smoking and dietary measures the loss of kidney
      function can often be slowed down or even stopped. The most common types of
      glomerulonephritis in Western Europe comprise IgA-nephropathy, membranous
      glomerulonephritis and rapidly progressive glomerulonephritis (RPGN). 

PMID- 23860683
TI  - [Autonomic neuropathies--diagnosis and evidence based treatment].
AB  - Among the few well-established techniques to diagnose autonomic dysfunction are
      head-up-tilt table testing, heart rate variability measurement and axon-reflex
      based sudomotor testing. Recent research focused on the development of novel
      techniques to assess autonomic function based on axon-reflex testing in both
      vasomotor and pilomotor nerve fibers. However, these techniques are clinically
      not widely used due to technical limitations and the lack of data on their
      utility to detect autonomic dysfunction in patients with neuropathy. The
      treatment of autonomic neuropathies should focus on the management of the
      underlying disease. In addition, symptomatic treatment of autonomic dysfunction
      should be provided in an individual patient-centered multimodal regimen that may
      incorporate both pharmacological and non-pharmacological strategies. The use of
      medication in autonomic dysfunction requires a careful risk-benefit assessment
      and should be individually adjusted based on both therapeutic success and
      occurrence of adverse effects. 

PMID- 23860684
TI  - [Cryptococcosis: case reports, epidemiology and treatment options].
AB  - Cryptococcosis is a fungal infection that is usually caused by Cryptococcus
      neoformans. Given the decreasing number of cases in HIV-infected patients in
      developed countries, infections in other patient populations, such as solid organ
      transplant recipients, patients with chronic organ diseases or even patients
      without immunodeficiency gain more attention. Due to a possible involvement of
      many organs, the clinical presentation varies from localized infections of the
      respiratory tract and the skin, to the characteristic meningoencephalitis or
      other organs after hematogenous dissemination. Sensitive laboratory tests allow a
      rapid diagnosis in patients with disseminated infection. Crucial therapeutic
      decisions depend on the underlying patient condition and the particular organ
      involvement. The induction therapy of disseminated infections or severe localised
      infections is based on amphotericin B in combination with 5-flucytosine. In non
      severe localised infections and after induction therapy, antifungal treatment
      with fluconazole is indicated. Echinocandins are not effective in cryptococcosis.

PMID- 23860685
TI  - Magnetostrictive thin films for microwave spintronics.
AB  - Multiferroic composite materials, consisting of coupled ferromagnetic and
      piezoelectric phases, are of great importance in the drive towards creating
      faster, smaller and more energy efficient devices for information and
      communications technologies. Such devices require thin ferromagnetic films with
      large magnetostriction and narrow microwave resonance linewidths. Both properties
      are often degraded, compared to bulk materials, due to structural imperfections
      and interface effects in the thin films. We report the development of epitaxial
      thin films of Galfenol (Fe81Ga19) with magnetostriction as large as the best
      reported values for bulk material. This allows the magnetic anisotropy and
      microwave resonant frequency to be tuned by voltage-induced strain, with a larger
      magnetoelectric response and a narrower linewidth than any previously reported
      Galfenol thin films. The combination of these properties make epitaxial thin
      films excellent candidates for developing tunable devices for magnetic
      information storage, processing and microwave communications. 

PMID- 23860686
TI  - An additional substrate binding site in a bacterial phenylalanine hydroxylase.
AB  - Phenylalanine hydroxylase (PAH) is a non-heme iron enzyme that catalyzes
      oxidation of phenylalanine to tyrosine, a reaction that must be kept under tight
      regulatory control. Mammalian PAH has a regulatory domain in which binding of the
      substrate leads to allosteric activation of the enzyme. However, the existence of
      PAH regulation in evolutionarily distant organisms, for example some bacteria in
      which it occurs, has so far been underappreciated. In an attempt to
      crystallographically characterize substrate binding by PAH from Chromobacterium
      violaceum, a single-domain monomeric enzyme, electron density for phenylalanine
      was observed at a distal site 15.7 A from the active site. Isothermal titration
      calorimetry (ITC) experiments revealed a dissociation constant of 24 +/- 1.1 MUM
      for phenylalanine. Under the same conditions, ITC revealed no detectable binding
      for alanine, tyrosine, or isoleucine, indicating the distal site may be selective
      for phenylalanine. Point mutations of amino acid residues in the distal site that
      contact phenylalanine (F258A, Y155A, T254A) led to impaired binding, consistent
      with the presence of distal site binding in solution. Although kinetic analysis
      revealed that the distal site mutants suffer discernible loss of their catalytic
      activity, X-ray crystallographic analysis of Y155A and F258A, the two mutants
      with the most noticeable decrease in activity, revealed no discernible change in
      the structure of their active sites, suggesting that the effect of distal binding
      may result from protein dynamics in solution. 

PMID- 23860687
TI  - Genetic association analysis of ITGB3 polymorphisms with age at onset of
      schizophrenia.
AB  - Schizophrenia (SCZ) is a debilitating disorder with a prevalence of approximately
      1 % worldwide. SCZ is known to have a high degree of genetic and clinical
      heterogeneity and is a major health problem worldwide. The integrin-beta 3
      subunit gene (ITGB3) gene at 17q21.32 has been implicated in psychiatric
      disorders. We therefore hypothesized that ITGB3 gene polymorphisms might also
      play a role in SCZ and age at onset (AAO) of SCZ. We investigated the genetic
      associations of 23 single-nucleotide polymorphisms (SNPs) of the ITGB3 gene with
      AAO in SCZ in two Caucasian samples (2,166 cases and 2,525 controls) using linear
      regression analysis and meta-analysis. We observed four ITGB3-SNPs associated
      with AAO in SCZ in a non-Genetic Association Information Network (GAIN) sample (p
      < 10(-3)). Three of these four SNPs were replicated in the GAIN sample. The SNP
      rs16941771 was most significantly associated with AAO (p = 7.47 * 10(-5)). Meta
      analysis showed that 6 of 23 SNPs were associated with AAO. The haplotype
      analysis also supports the association of ITGB3 with AAO. Three disease
      associated SNPs were located at species-conserved regions, indicating functional
      importance. This is the first report which shows that ITGB3 variants are
      associated with AAO in SCZ, providing direct evidence of the use of AAO as an
      intermediate phenotype to dissect the complex genetics of SCZ.

PMID- 23860688
TI  - FOXO3a involvement in the release of TNF-alpha stimulated by ATP in spinal cord
      astrocytes.
AB  - Spinal cord injury is characterized by an inflammatory response that includes the
      increased expression of several cytokines and chemokines. Extracellular adenosine
      triphosphate (ATP) acts as a critical endogenous signaling molecule in
      inflammation and immunity. However, the molecular and cellular mechanisms of the
      proinflammatory cytokines stimulated by ATP are poorly understood. Mammalian
      forkhead members of the class O (FOXO) are involved in a variety of signaling
      pathways. In this study, we have found that ATP could selectively decrease the
      expression of FOXO1 and FOXO3a via the phosphorylation of epidermal growth factor
      receptor (EGFR) and Akt in spinal cord astrocytes. However, ATP had no effect on
      the expression of FOXO4 and FOXO6, and EGFR, Akt, and ERK1/2 all involve in the
      release of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) induced
      by ATP. In addition, we have researched that the overexpressed FOXO3a could
      specially inhibit the release of TNF-alpha increased by ATP, but the level of IL
      6 induced by ATP was not decreased. Meanwhile, there was no change in the release
      of IL-6 and TNF-alpha after FOXO1 was overexpressed. Understanding the critical
      role of FOXO3a in astrocytes stimulated by ATP may provide a potential target for
      therapeutic intervention after spinal cord injury. 

PMID- 23860690
TI  - Neck of femur fractures in the over 90s: a select group of patients who require
      prompt surgical intervention for optimal results.
AB  - BACKGROUND: Patients in the extremes of old age with a femoral neck fracture
      represent a challenging subgroup, and are thought to be associated with poorer
      outcomes due to increased numbers of comorbidities. Whilst many studies are aimed
      at determining the optimum time for surgical fixation, there is no agreed
      consensus for those over 90. The aim of this study is to report the surgical
      outcome of this population, to understand the role surgical timing may have on
      operative outcomes using the orthopaedic POSSUM scoring system and to identify
      whether medical optimization occurs during the period of admission before
      surgery. MATERIALS AND METHODS: We conducted a prospective observational study;
      data was collected from two district general hospitals over 32 consecutive
      months. All patients aged 90 and above who were deemed suitable for surgical
      fixation were included. Each one had their orthopaedic POSSUM score calculated at
      admission and at surgery, using their computerised and paper medical records.
      Assessment of outcome was based on morbidity and mortality at 30 days. RESULTS: A
      total of 146 consecutive patients above the age of 90 underwent surgery and were
      followed. The average age of the patients was 93 years, 123 (84 %) were female
      and 23 (16%) male. Sixty-one patients were operated on within 24 h from
      admission, 52 patients within 24 and 48 h and 33 had surgery after 48 h from
      admission. In total, 21 deaths (14.4%) were recorded and 81 patients (55.5%) had
      a post-operative complication within 30 days. The orthopaedic POSSUM scoring
      system predicted 30-day mortality in 23 patients and morbidity in 83 patients.
      This gave observed to predicted ratios of 0.91 and 0.98 respectively. Overall,
      there was a small improvement in physiological scores taken just prior to surgery
      compared to those at admission. Mortality and morbidity rates were higher for
      those operated on or after 24 and 48-h cutoffs compared to those proceeding to
      surgery within 24 h (P = 0.071 and P = 0.021 respectively and P = 0.048 and P =
      0.00011 respectively). When stratified according to their POSSUM scores, patients
      with scores of 41+ and surgery after 48 h had a significantly higher mortality
      rate than if they had surgery earlier (P = 0.038). Morbidity rates rose after 24
      h of surgical delay (P = 0.026). Patients with a total POSSUM score between 33
      and 40 exhibited a higher morbidity after a 24-h delay to surgery (P = 0.0064).
      CONCLUSION: As life expectancy increases, older patients are becoming commoner in
      our hospital systems. We believe the orthopaedic POSSUM scoring system can be
      used as an adjuvant tool in prioritising surgical need, and allow for a more
      impartial evaluation when changes to practice are made. Our findings show that
      timing of surgery has an important bearing on mortality and morbidity after hip
      surgery, and older patients with higher orthopaedic POSSUM scores are sensitive
      to delays in surgery.

PMID- 23860689
TI  - On the origins of the androgen receptor low molecular weight species.
AB  - Prostate cancer (CaP), a commonly diagnosed malignancy, is readily treated by
      androgen ablation. This treatment temporarily halts the disease, but castration
      resistant neoplasms that are refractory to current therapies emerge. While these
      neoplasms are no longer dependent on physiological levels of androgens, they
      remain reliant on the expression of the androgen receptor (AR). There are
      multiple mechanisms by which CaP cells circumvent androgen ablation therapies.
      These include AR mutations that broaden ligand specificity, AR overexpression, AR
      activation by growth factors and cytokines, overexpression of AR co-activators,
      altered steroid metabolism, and a locus-wide histone transcriptional activation
      of some AR targets. This review focuses on a more recently described mechanism:
      the expression of low molecular weight AR species that are missing the ligand
      binding domain and function independently of ligand to drive proliferation. The
      etiology, biological activity, unique features, predictive value, and therapeutic
      implication of these androgen receptor isoforms are discussed in depth. 

PMID- 23860691
TI  - Guest editorial: Organ trafficking and transplant tourism: a call for
      international collaboration.

PMID- 23860692
TI  - Work-life balance of German gynecologists: a web-based survey on satisfaction
      with work and private life.
AB  - PURPOSE: Work-life balance is an upcoming issue for physicians. The working group
      "Family and Career" of the German Society for Gynecology and Obstetrics (DGGG)
      designed a survey to reflect the present work-life balance of female and male
      gynecologists in Germany. METHODS: The 74-item, web-based survey "Profession
      Family-Career" was sent to all members of the DGGG (n = 4,564). In total, there
      were 1,036 replies (23%) from 75% female gynecologists (n = 775) aged 38 +/- 7
      (mean +/- standard deviation [SD]) years and 25% male (n = 261) gynecologists
      aged 48 +/- 11 years. Statistical analyses were performed using the mean and SD
      for descriptive analysis. Regression models were performed considering an effect
      of p <= 0.05 as statistically significant. RESULTS: 47% women and 46% men
      reported satisfaction with their current work-life balance independent of gender
      (p(gender) = 0.15). 70% women and 75 % men answered that work life and private
      life were equally important to them (p(gender) = 0.12). While 39% women versus
      11% men worked part-time (p gender < 0.0001), men reported more overtime work
      than women (p(gender) < 0.0001). 75 % physicians were not satisfied with their
      salary independent of gender (p(gender) = 0.057). Work life affected private life
      of men and women in a similar way (all p(gender) > 0.05). At least 37% women and
      men neglected both their partner and their children very often due to their work.
      CONCLUSIONS: Female physicians often described their work situation similar to
      male physicians, although important differences regarding total work time,
      overtime work and appreciation by supervisors were reported. Work life affected
      private life of women and men in a similar way.

PMID- 23860693
TI  - Elevated diastolic blood pressure in insulin-resistant polycystic ovarian
      syndrome patients.
AB  - OBJECTIVE: The purpose of this study was to further understand interrelationships
      between insulin resistance in PCOS and elevated diastolic blood pressure. DESIGN:
      A prospective case control study. PARTICIPANTS: Fifty normal women and 43 PCOS
      patients, 16 of them with insulin resistance. SETTING: Academic Institution.
      INTERVENTIONS: Clinical, anthropometric and ultrasonographic features of PCOS
      were assessed, as were blood levels for luteinizing hormone, follicle-stimulating
      hormone, androstenedione, DHEAS, and basal insulin. A lipid profile and an oral
      glucose tolerance test (OGTT) were also performed. MAIN OUTCOME MEASURES: To
      demonstrate the effect of insulin resistance on blood pressure in patients with
      PCOS. RESULTS: Patients with PCOS and those with PCOS plus insulin resistance
      (IR) had significantly elevated levels of plasma androgen but only those with IR
      showed greater body mass index and waist: hip ratios than PCOS or control. PCOS
      plus IR differed significantly in their response to OGTT when compared to PCOS or
      control. Alterations in lipid profile were shown to be atherogenic. Patients with
      PCOS plus IR demonstrated a significant elevation of diastolic blood pressure
      when compared to PCOS alone or controls. CONCLUSIONS: We hypothesize that
      hyperlipidemia and IR may be involved in the pathophysiologic features of the
      elevated diastolic blood pressure in PCOS patients.

PMID- 23860694
TI  - A new model using platelet indices to predict liver fibrosis in patients with
      chronic hepatitis B infection.
AB  - BACKGROUND: We aimed to investigate whether mean platelet volume (MPV) and
      platelet distribution width (PDW) are variables determining the severity of liver
      fibrosis in patients with chronic HBV infection. METHODS: Patients were divided
      into two groups with fibrosis scores of 0-2 and 3-6 (according to Ishac scoring
      system). Whether MPV and PDW were independent variables determining the severity
      of liver fibrosis score or not was investigated by comparing these groups.
      RESULTS: Of the 111 cases, 74 (66.7 %) were male (mean age 37.7 +/- 11.6 years).
      Twenty-two of the cases (19.8 %) were HBeAg-positive. Fibrosis scores of 42 cases
      (37.8 %) were >= 3 and the remaining 69 cases had fibrosis scores < 3 (62.2 %).
      Independent variables determining the severity of fibrosis score were low levels
      of albumin and mean platelet volume, and high levels of prothrombin time and PDW
      (Odds ratio (95 % confidence interval) and p values were 0.105 (0.018-0.605) and
      0.012 for albumin, 0.402 (0.234-0.692) and 0.001 for mean platelet volume, 1.529
      (1.183-1.975) and 0.001 for PDW, and 0.924 (0.875-0.976) and 0.005 for
      prothrombin time, respectively). The sensitivity, specificity, positive
      predictive value and negative predictive value of regression model that is
      established using above mentioned parameters were 88.1, 75.3, 68.5, and 91.7 %,
      respectively (AUC = 0.886, p = 0.0001). CONCLUSIONS: MPV and PDW are independent
      variables determining the severity of liver fibrosis, and the regression model
      that is established using these parameters along with other markers, may give
      more information about the severity of liver fibrosis.

PMID- 23860695
TI  - Effects of sevoflurane and desflurane on oxidative stress during general
      anesthesia for elective cesarean section.
AB  - BACKGROUND: Anesthetic agents might considerably influence maternal-fetal
      oxidative stress and antioxidants during cesarean section (CS). The aim of this
      study was to investigate the effects of desflurane and sevoflurane on oxidative
      stress parameters both in mothers and newborns undergoing elective CS. MATERIALS
      AND METHODS: Eighty ASA physical status I-II, term parturients undergoing
      elective CS under general anesthesia were randomized to desflurane (Group D) and
      sevoflurane (Group S) groups. Blood samples were collected from mothers before
      operation and postoperatively and umbilical artery samples were obtained at
      delivery. Total oxidant status (TOS), total antioxidant capacity (TAC) status,
      lipid hydroperoxide (LOOH), and free sulfhydryl (-SH) levels were measured and
      oxidative stress index was calculated. Secondary outcomes included maternal
      hemodynamics. RESULTS: Preoperative LOOH, TOS, OSI, TAC, and -SH levels were
      similar among groups. Postoperative maternal serum LOOH, TOS, and OSI levels were
      significantly increased in Group D compared to Group S (p = 0.003, p = 0.005, p =
      0.04; respectively). Postoperative umbilical artery LOOH, TOS, OSI levels were
      also significantly increased in Group D compared to Group S (p = 0.04, p = 0.02,
      p = 0.01; respectively). Postoperative TOS (p = 0.001, < 0.001 respectively) and
      OSI (p = 0.003, < 0.001 respectively) levels in both Group D and Group S were
      statistically significantly decreased compared to preoperative levels.
      Postoperative LOOH and -SH levels in Group S (p = 0.04, 0.029 respectively) were
      statistically significantly decreased compared to preoperative levels. There were
      no significant differences in TAC and -SH levels among groups (p = nonsignificant
      [n.s.]). Maternal perioperative mean blood pressure and heart rate were similar
      among groups (p = n.s.). CONCLUSION: Oxidative stress indices might be modified
      with preferred anesthetic agent and sevoflurane showed more favorable effects
      than desflurane in view of oxidative stress.

PMID- 23860696
TI  - A rare cause of acute coronary syndrome: electrical shock.
AB  - Electrical shock can cause death, disability, and any degree of damage to various
      organs and systems. Coronary angiography (CA) could help us for underlying
      condition, and for treatment choice. Herein, we reported electrical shock
      insulted patient whose electrocardiography showed anterior ST elevation, such as
      myocardial infarction electrocardiographic findings with angiographically normal
      coronary arteries. 

PMID- 23860697
TI  - Unmeasured anions are associated with short-term mortality in patients with
      hypoxic hepatitis.
AB  - OBJECTIVE: Hypoxic hepatitis is a common cause of hepatic impairment in
      critically ill patients and is an independent risk factor for mortality. An
      elevated level of unmeasured anions is another unfavourable prognostic marker in
      many disease entities. While the biochemical nature of unmeasured anions is
      unknown, data suggest that they may be released from the liver. Therefore, the
      purpose of this study was to determine whether the strong ion gap-the gold
      standard for estimation of unmeasured anions-is elevated and associated with
      outcome in patients with hypoxic hepatitis. METHODS: One hundred and five
      consecutive patients with hypoxic hepatitis admitted to the (intensive care unit)
      ICU of a university hospital were prospectively included in the study and
      compared with 15 healthy controls. RESULTS: Compared with the controls, patients
      with hypoxic hepatitis had an elevated strong ion gap (4.0 +/- 2.6 vs. 7.8 +/-
      4.0 mmol/L; p = 0.0002) that contributed to metabolic acidosis. Patients dying
      within 5 days had a larger strong ion gap upon admission than did patients
      surviving beyond 5 days. The mean strong ion gap (SIG) over the course of the
      first 5 days after admission to the ICU was 1.3 mmol/L (0.3-2.3 mmol/L) larger in
      patients who died compared with patients who survived, p = 0.008. In multivariate
      Cox-regression, larger strong ion gaps were associated with shorter survival
      time. The SIG correlated positively with both AST and ALT. CONCLUSIONS:
      Unmeasured anions are elevated in patients with hypoxic hepatitis, contribute to
      metabolic acidosis and are associated with mortality. The liver is a possible
      source of the unmeasured anions, which may represent markers of tissue damage in
      hypoxic hepatitis.

PMID- 23860698
TI  - A hand surgeon's advanced experience with thoracic outlet compression syndrome.
AB  - Although hand surgeons may often see patients with arm and hand pain, numbness
      and tingling in their practice, the possibility of the presence of thoracic
      outlet compression syndrome (TOCS) is not often considered. In our practice
      almost half of newly referred patients have the complaint of upper extremity
      pain, numbness and tingling. In approximately 50% of these patients detailed
      history and physical examination are suggestive of TOCS. For this reason it is
      quite important to recognize the possibility of the existence of this condition.
      Very often in the past, and occasionally today, this condition has been
      considered a controversial subject by numerous physicians because of the absence
      of objective findings in many patients. For several years it has been very well
      known that the objective findings are present in about 10% of patients and the
      remaining 90% of patients have subjective complaints. For this reason it has been
      one of the most commonly underrated, overlooked, and misdiagnosed conditions.
      During the last 22 years our experience with combined surgical approach for this
      condition (transaxillary first rib resection with immediate transcervical
      anterior and middle scalenectomy) has been quite satisfactory. During these years
      over 850 of these procedures were performed. Between 1989 and 2002 (13 years) 532
      patients from a wide geographic area had this combined approach procedure. We
      were able to locate 358 of these patients for follow-up and of those only 102
      responded to our questionnaire. Of the 102 who responded, 95 reported improvement
      of their symptoms. From 2003 to the middle of 2012, 350 patients from a wide
      region had this combined procedure. We sent a questionnaire to these patients and
      had only 57 to respond. Of those who responded, there were 19 bilateral
      interventions performed a few months apart, with a total of 76 procedures
      performed. Results based on these 76 procedures revealed 95% improvement of their
      symptoms. This combined approach for TOCS is the most complete intervention with
      high rate of improvement and low rate of recurrences. 

PMID- 23860699
TI  - [Comment on the manuscript "A hand surgeon's advanced experience with thoracic
      outlet compression syndrome", by Erdogan Atasoy].

PMID- 23860700
TI  - [Malignant bone tumors of the hand].
AB  - Malignant bone tumors are very rare entities in the bones of the hand. The
      histologic subtypes (chondrosarcoma, osteosarcoma, Ewing-sarcoma) preferentially
      manifest in varying regions of the skeleton. Chondrosarcomas are the most
      frequent malignant bone tumor type in the hand. Cardinal symptoms of malignant
      bone tumors in the hand and in general are a new swelling and pain in the
      affected bones. The primary diagnostic tools are radiologic techniques (x-ray,
      CT, MRI) for assessment of local tumor growth and the oncologic staging. A
      definitive treatment of malignant bone tumors should be carried out in
      specialized centers, as these tumors are rare. Surgical therapy is completed by
      chemo- or radiotherapy, if required because of histologic subtype and local or
      systemic spreading. Safe margins of tumor resection should be preferred to
      function-preserving treatment for tumors of the hand while the preservation of
      functional units should be pursued whenever possible. 

PMID- 23860701
TI  - [Comment on overview "Malignant bone tumors of the hand"].

PMID- 23860702
TI  - [Arterialized venous free flaps for resurfacing hand and finger defects].
AB  - BACKGROUND: Soft tissue defects on the hand and on the fingers with exposed
      functional structures require a thin and sturdy closure. If skin grafts or local
      flaps are not possible the arterialized venous free flaps represent a good
      alternative. PATIENTS AND METHODS: This retrospective study included all
      arterialized venous free flaps used for hand and finger defects since 2005. We
      evaluated type and technique (for example antegrade vs. retrograde arterial
      inflow and the number of veins) and size of the flaps. Flap harvesting time was
      also examined. RESULTS: 11 venous flaps were used for resurfacing hand and finger
      defects. Most of them were retrogradely arterialized. 10 of 11 flaps healed
      uneventfully. Due to a thrombosis in an outflowing vein one flap was lost at the
      sixth postoperative day. Median size of the arterialized flaps was 6*4 cm and the
      median time for flap harvest was 38 (27-51) min. The donor site was primarily
      closed in 2 cases and in 9 cases with a skin graft. CONCLUSION: Arterialized
      venous free flaps represent a reliable and safe option for resurfacing hand and
      finger defects. Easy and fast harvesting due to the visible venous vascular
      system is an advantage. The flaps are thin, pliable and can be easily adjusted to
      the needs of the defect. Using conservative measures it is possible to control
      side effects like venous pooling, swelling and purplish discoloration. With
      arterialized venous free flaps early hand therapy is possible, in contrast to
      heterodigital and local flaps. In comparison to other free flaps it is not
      necessary to sacrifice an artery at the donor site.

PMID- 23860703
TI  - [Early functional treatment of intra-articular fractures of the proximal
      interphalangeal joint of the finger using a modified traction device].
AB  - INTRODUCTION: Treatment of intra-articular fractures of the middle phalanx is
      both difficult and controversial. We report our experience of using a modified
      dynamic traction device (mTD) utilizing only one pin in the head of the middle
      phalanx and thus facilitating further open reconstructive surgery at the proximal
      interphalangeal joint (PIP). The pin does not necessarily have to be inserted in
      the movement axis of the joint. AIM OF THE STUDY: The aim of the study was to a)
      determine the effectiveness of the mTD, particularly in comparison with other
      distraction systems used in the treatment of middle phalanx fractures as
      described in the literature, and b) compare the results of patients treated using
      an mTD only with the results of those treated with an mTD in combination with
      additional open reconstructive surgery. PATIENTS AND METHODS: 26 patients with a
      mean age of 37 years were treated for intra-articular fractures of the base of
      the middle phalanx using an mTD in the period between 2007 and 2011. 13 of these
      patients also underwent additional open reconstructive surgery. 18 of the 26
      patients (69%) were reevaluated after 33 months (range 9-44 months); 10 of these
      had undergone additional open reconstructive surgery. Follow-up of 14 of the
      patients included their completion of a structured questionnaire and calculation
      of their DASH scores as well as radiological and clinical examinations. 4
      patients completed the questionnaire and had their DASH score calculated.
      Measurement of range of motion was performed by the treating general
      practitioner. Patient records were analysed with a particular focus on
      complications and duration of therapy. RESULTS: The mTD was used for an average
      of 34 days (range 8-53 days) and overall treatment took an average of 74 days
      (range 66-154 days). 4 pin tract infections were reported. The mean DASH score
      was 6.4. The mean range of motion in the PIP joint was 70 degrees  (range 30-110
      degrees ). The range of motion of the PIP and DIP joints (61o) was significantly
      poorer in patients with additional surgery than that (82o) in patients with sole
      mTD treatment. Treatment with the mTD gave results similar to those obtained with
      other distraction devices with good subjective evaluation by the patients.
      CONCLUSION: Dynamic traction with the help of the modified traction devices is
      suitable for treating intra-articular fractures of the proximal interphalangeal
      joint, as demonstrated by a comparison with the literature. Patients who
      underwent additional open surgery showed less favorable results. The present
      method has the advantage that only one wire needs to be inserted subcapitaly at a
      distance from the fracture in the middle finger and this facilitates further
      surgical interventions.

PMID- 23860704
TI  - [Psammomatous tenosynovialitis of hand and forearm - three new cases].
AB  - We report about three new observations of psammomatous tenosynovialitis on hand
      and forearm and performed a review of literature. To the best of our knowledge
      cases 7, 8 and 9 in the medical literature are now published. 

PMID- 23860705
TI  - [Relapse of a parosteal osteochondromateous proliferation (Nora's lesion) of the
      distal thumb].
AB  - We report the case of a 29-year-old female patient with a relapse of a Nora
      lesion in an atypic location. The literature for this rare benign lesion is
      reviewed and etiology, diagnostics and therapy are discussed.

PMID- 23860706
TI  - [Spontaneous fixation of MP-joint of the index finger in flexion].
AB  - Spontaneous fixations of MP-joints of fingers and thumbs are rare and are often a
      challenging task for hand surgeons. We present a 25-year-old female office
      employee with a fixed painless MP-joint of the left index finger in 90 degrees 
      flexion with normal PIP- und DIP-joint range of motion. Using the palmar approach
      to the MP-joint the entrapped accessory collateral ligament which was constrained
      by a prominent radial condylus could be identified. Operative removal of the
      prominence has released the joint. An uncomplicated wound healing has followed
      with completely unrestricted range of motion. If a closed reduction should be
      considered, it ought to be done cautiously without anaesthetics. A failed 
      reduction entails an operative revision using the palmar approach. 

PMID- 23860707
TI  - Chronic, refractory CRPS involving 3 limbs: a case report.
AB  - We report the case of a 26-year-old woman with CRPS involving consecutively 3
      extremities during 8 years. None of the treatments used was effective and each
      CRPS episode resulted in persistence and chronification of the disease. We
      suggest that this patient presents a specific subtype of the disease, called
      "chronic, refractory CRPS" which is extremely severe, disabling and resistant to
      treatment. 

PMID- 23860708
TI  - Serum calcium and the calcium-sensing receptor polymorphism rs17251221 in
      relation to coronary heart disease, type 2 diabetes, cancer and mortality: the
      Tromso Study.
AB  - Serum calcium measured in 27,158 subjects in 1994 and the calcium-sensing
      receptor polymorphism rs17251221 genotyped in 9,404 subjects were related to
      cardiovascular risk factors, incident myocardial infarction (MI), type 2 diabetes
      (T2DM), cancer and death during follow-up until 2008-2010. In a Cox regression
      model with adjustment for age, gender, smoking and body mass index, subjects with
      serum calcium 2.50-2.60 mmol/L had a significantly increased risk of incident MI
      [n = 1,802, hazards ratio (HR) 1.40, 95 % confidence interval (CI) 1.18, 1.66]
      and T2DM (n = 705, HR 1.49, 95 % CI 1.15, 1.94) and a significantly reduced risk
      of cancer (n = 2,222, HR 0.73, 95 % CI 0.62, 0.86) as compared to subjects with
      serum calcium 2.20-2.29 mmol/L. For rs17251221 there was a mean difference in
      serum calcium of 0.05 mmol/L between major and minor homozygote genotypes. No
      consistent, significant relation between rs17251221 and risk factors or the major
      hard endpoints were found. The minor homozygote genotype (high serum calcium) had
      a significant twofold increased risk (HR 2.32, 95 % CI 1.24, 4.36) for prostate
      cancer, as compared to the major homozygote. This may be clinically important if
      confirmed in other cohorts. 

PMID- 23860709
TI  - Better risk assessment with glycated hemoglobin instead of cholesterol in CVD
      risk prediction charts.
AB  - Traditional risk charts for the prediction of cardiovascular disease (CVD)
      include cholesterol parameters. We evaluated how models predict fatal CVD when
      cholesterol is replaced by glucose parameters. We used data from NHANES III, a US
      survey conducted 1988-1994 (follow-up until 2006); 15,454 participants (1,716 CVD
      deaths) were included. Based on the ESC SCORE method, we used age, sex, blood
      pressure, smoking and either of the following: (1) total cholesterol, (2) total
      to-HDL-cholesterol, (3) glucose, (4) glycated hemoglobin (A1C). Scaled Brier
      score (BS), Nagelkerke's R(2) (NR) and integrated discrimination improvement
      (IDI) were used for model comparison. The ranking (best to worst) was: A1C (BS =
      11.62 %; NR = 0.0865; IDI = 0.0091), glucose (11.16 %; 0.0734; 0.0067), total-to
      HDL-cholesterol (9.97 %; 0.0547; 0.0010), cholesterol (9.75 %; 0.0484; 0,
      reference). Differences between models with cholesterol and glucose or A1C were
      statistically significant. This study suggests the use of A1C instead of
      cholesterol parameters in charts to assess CVD risk. 

PMID- 23860711
TI  - Use of an in vitro flat-bed biofilm model to measure biologically active anti
      odour compounds.
AB  - The objective of this study was to demonstrate the utility of a modified flat-bed
      perfusion biofilm matrix system for testing toothpaste formulations directly,
      without dilution, as a layer in direct contact with the biofilm matrix surface.
      Final biofilm yields and volatile sulphur compounds (VSC) biogenesis were
      measured to show the relative efficacy of toothpaste formulations. Diffusion
      characteristics of the flat-bed system to exposure with Meridol(r) tooth and
      tongue gel (TTG; 1,400 ppm F(-) from amine fluoride/stannous fluoride, 0.5 % zinc
      lactate, oral malodour counteractives) was assessed using a bioluminescent target
      species Escherichia coli Nissle 1917/pGLITE coupled with a low-light photon
      camera to visualise the kill kinetics. Tongue-flora derived, mixed culture
      biofilms (n = 4) received 5, 15 and 30 min treatment with TTG, respectively, to
      determine the optimum time of exposure. VSC biogenesis was measured from
      headspace samples by gas chromatography prior to and following treatment of two
      daily applications for 4 days of treatment (TTG), positive control (CHX gel) and
      negative controls (placebo and sham treatment). Viable counts were performed at
      the end of experiments by destructive sampling of the biofilms and plating onto
      selective and non-selective agar. Following a single treatment with TTG, the E.
      coli biofilm with lux target gave >50 % reduction of luminescence within 2 to 3 h
      before recovering to a steady state over 10 h, suggesting biofilm cidal activity
      rather biostasis. For mixed culture biofilms, 15- and 30-min treatment exposure
      with TTG gave almost identical reductions in final biofilm yields. For comparing
      efficacy of treatments, biofilms treated with TTG gave greatest reductions in
      both pre-post levels of H2S (P < 0.01) and CH3SH (P < 0.05) and population yields
      at the end of the experiments (P < 0.001) compared to placebo and positive
      control. The in vitro flat-bed perfusion model may be used to replicate many of
      the activities and reactions believed to be occurring by the tongue biofilm
      microflora within a real mouth, including VSC biogenesis and its inhibition by
      exposure to active agents as components of toothpastes and gels applied in direct
      contact with the biofilm. 

PMID- 23860712
TI  - Trp358 is a key residue for the multiple catalytic activities of multifunctional
      amylase OPMA-N from Bacillus sp. ZW2531-1.
AB  - The oligosaccharide-producing multifunctional amylase-N (OPMA-N) is a novel
      multifunctional amylase and exhibits both hydrolytic and transglycosyl
      activities, but the molecular mechanism for its multiple catalytic activities is
      still unknown. Our research investigates the possible catalytic roles of a Trp
      residue in OPMA-N (Trp358) which is not only near the catalytic site Glu356 but
      also highly conserved in glycoside hydrolase subfamily 20 (the neopullulanase
      subfamily). Site-directed mutageneses at this site reveal that the size and
      charge of the occupying amino acid directly affect substrate binding, orientation
      of other crucial catalytic residues, the catalytic specificity, the oligomer
      formation, as well as the thermal stability of the enzyme. These findings may be
      useful in elucidating the different mechanisms of the multiple catalytic
      activities of multifunctional amylase OPMA-N and hence for developing an improved
      multifunctional amylase for the preparation of isomaltooligosaccharides. 

PMID- 23860713
TI  - Identification of microorganisms by FTIR spectroscopy: perspectives and
      limitations of the method.
AB  - Fourier transform infrared (FTIR) spectroscopy was introduced in 1991 as a
      technique to identify and classify microbes. Since then, it has gained growing
      interest and has undergone a remarkable evolution. Highly sophisticated
      spectrometers have been developed, enabling a high sample throughput. Today, the
      generation of high-quality data in a short time and the application of the
      technique for rapid and reliable identification of microbes to the species level
      are well documented. What makes FTIR spectroscopy even more attractive is the
      fact that spectral information can also be exploited for strain typing purposes,
      which is particularly important for epidemiological analyses and some
      technological applications. Accordingly, in recent years, FTIR spectroscopy has
      been increasingly used for typing and classifying microorganisms below the
      species level. The intention of this review is to give an overview over current
      knowledge and strategies of using FTIR spectroscopy for species identification
      and to describe different approaches for strain typing. 

PMID- 23860715
TI  - Experimental violation and reformulation of the Heisenberg's error-disturbance
      uncertainty relation.
AB  - The uncertainty principle formulated by Heisenberg in 1927 describes a trade-off
      between the error of a measurement of one observable and the disturbance caused
      on another complementary observable such that their product should be no less
      than the limit set by Planck's constant. However, Ozawa in 1988 showed a model of
      position measurement that breaks Heisenberg's relation and in 2003 revealed an
      alternative relation for error and disturbance to be proven universally valid.
      Here, we report an experimental test of Ozawa's relation for a single-photon
      polarization qubit, exploiting a more general class of quantum measurements than
      the class of projective measurements. The test is carried out by linear optical
      devices and realizes an indirect measurement model that breaks Heisenberg's
      relation throughout the range of our experimental parameter and yet validates
      Ozawa's relation. 

PMID- 23860716
TI  - Assessing association between protein truncating variants and quantitative
      traits.
AB  - MOTIVATION: In sequencing studies of common diseases and quantitative traits,
      power to test rare and low frequency variants individually is weak. To improve
      power, a common approach is to combine statistical evidence from several genetic
      variants in a region. Major challenges are how to do the combining and which
      statistical framework to use. General approaches for testing association between
      rare variants and quantitative traits include aggregating genotypes and trait
      values, referred to as 'collapsing', or using a score-based variance component
      test. However, little attention has been paid to alternative models tailored for
      protein truncating variants. Recent studies have highlighted the important role
      that protein truncating variants, commonly referred to as 'loss of function'
      variants, may have on disease susceptibility and quantitative levels of
      biomarkers. We propose a Bayesian modelling framework for the analysis of protein
      truncating variants and quantitative traits. RESULTS: Our simulation results show
      that our models have an advantage over the commonly used methods. We apply our
      models to sequence and exome-array data and discover strong evidence of
      association between low plasma triglyceride levels and protein truncating
      variants at APOC3 (Apolipoprotein C3). AVAILABILITY: Software is available from
      http://www.well.ox.ac.uk/~rivas/mamba

PMID- 23860718
TI  - Intestinal bacteria modify lymphoma incidence and latency by affecting systemic
      inflammatory state, oxidative stress, and leukocyte genotoxicity.
AB  - Ataxia-telangiectasia is a genetic disorder associated with high incidence of B
      cell lymphoma. Using an ataxia-telangiectasia mouse model, we compared lymphoma
      incidence in several isogenic mouse colonies harboring different bacterial
      communities, finding that intestinal microbiota are a major contributor to
      disease penetrance and latency, lifespan, molecular oxidative stress, and
      systemic leukocyte genotoxicity. High-throughput sequence analysis of rRNA genes
      identified mucosa-associated bacterial phylotypes that were colony-specific.
      Lactobacillus johnsonii, which was deficient in the more cancer-prone mouse
      colony, was causally tested for its capacity to confer reduced genotoxicity when
      restored by short-term oral transfer. This intervention decreased systemic
      genotoxicity, a response associated with reduced basal leukocytes and the
      cytokine-mediated inflammatory state, and mechanistically linked to the host cell
      biology of systemic genotoxicity. Our results suggest that intestinal microbiota
      are a potentially modifiable trait for translational intervention in individuals
      at risk for B-cell lymphoma, or for other diseases that are driven by
      genotoxicity or the molecular response to oxidative stress.

PMID- 23860719
TI  - Logical regulation of the enzyme-like activity of gold nanoparticles by using
      heavy metal ions.
AB  - In this study we employed self-deposition and competitive or synergistic
      interactions between metal ions and gold nanoparticles (Au NPs) to develop OR,
      AND, INHIBIT, and XOR logic gates through regulation of the enzyme-like activity
      of Au NPs. In the presence of various metal ions (Ag(+), Bi(3+), Pb(2+), Pt(4+),
      and Hg(2+)), we found that Au NPs (13 nm) exhibited peroxidase-, oxidase-, or
      catalase-like activity. After Ag(+), Bi(3+), or Pb(2+) ions had been deposited on
      the Au NPs, the particles displayed strong peroxidase-like activity; on the other
      hand, they exhibited strong oxidase- and catalase-like activities after reactions
      with Ag(+)/Hg(2+) and Hg(2+)/Bi(3+) ions, respectively. The catalytic activities
      of these Au NPs arose mainly from the various oxidation states of the surface
      metal atoms/ions. Taking advantage of this behavior, we constructed multiplex
      logic operations-OR, AND, INHIBIT, and XOR logic gates-through regulation of the
      enzyme-like activity after the introduction of metal ions into the Au NP
      solution. When we deposited Hg(2+) and/or Bi(3+) ions onto the Au NPs, the
      catalase-like activities of the Au NPs were strongly enhanced (>100-fold).
      Therefore, we could construct an OR logic gate by using Hg(2+)/Bi(3+) as inputs
      and the catalase-like activity of the Au NPs as the output. Likewise, we
      constructed an AND logic gate by using Pt(4+) and Hg(2+) as inputs and the
      oxidase-like activity of the Au NPs as the output; the co-deposition of Pt and Hg
      atoms/ions on the Au NPs was responsible for this oxidase-like activity.
      Competition between Pb(2+) and Hg(2+) ions for the Au NPs allowed us to develop
      an INHIBIT logic gate-using Pb(2+) and Hg(2+) as inputs and the peroxidase-like
      activity of the Au NPs as the output. Finally, regulation of the peroxidase-like
      activity of the Au NPs through the two inputs Ag(+) and Bi(3+) enabled us to
      construct an XOR logic gate. 

PMID- 23860720
TI  - A leathery lining.

PMID- 23860721
TI  - Capsule commentary on Long and Stavert, portfolios of biomedical HIV
      interventions in South Africa: a cost-effectiveness analysis.

PMID- 23860722
TI  - Early response to preventive strategies in the Diabetes Prevention Program.
AB  - BACKGROUND: Recommendations for diabetes prevention in patients with prediabetes
      include lifestyle modification and metformin. However, the significance of early
      weight loss and glucose measurements when monitoring response to these proven
      interventions is unknown. OBJECTIVE: To quantify the relationship between early
      measures of weight and glucose and subsequent diabetes in patients undergoing
      diabetes prevention interventions. DESIGN: Analysis of results from a randomized
      controlled trial in 27 academic medical centers in the United States.
      PARTICIPANTS/INTERVENTIONS: 3,041 adults with hyperglycemia randomized to
      lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete
      follow-up in The Diabetes Prevention Program. MAIN MEASURES: Independent
      variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months;
      hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main
      outcome was time to diabetes diagnosis. KEY RESULTS: After 6 months, 604
      participants developed diabetes in the lifestyle (n = 140), metformin (n = 206),
      and placebo (n = 258) arms over 2.7 years. In the lifestyle arm, 6-month weight
      loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI)
      0.65 (0.35-1.22), 0.62 (0.33-1.18), 0.46 (0.24-0.87), 0.34 (0.18-0.64), and 0.15
      (0.07-0.30) for 0-<3 %, 3-<5 %, 5-<7 %, 7-<10 %, and >=10 % weight loss,
      respectively (reference: weight gain). Attainment of optimal 6-month FG and HbA1c
      and 12-month post-load glucose predicted >60 % lower diabetes risk across arms.
      We found a significant interaction between 6-month weight loss and FG in the
      lifestyle arm (P = 0.038). CONCLUSION: Weight and glucose at 6 and 12 months
      strongly predict lower subsequent diabetes risk with a lifestyle intervention;
      lower FG predicts lower risk even with substantial weight loss. Early reduction
      in glycemia is a stronger predictor of future diabetes risk than weight loss for
      metformin. We offer the first evidence to guide clinicians in making interval
      management decisions for high-risk patients undertaking measures to prevent
      diabetes.

PMID- 23860723
TI  - High-density genotyping: an overkill for QTL mapping? Lessons learned from a case
      study in maize and simulations.
AB  - High-density genotyping is extensively exploited in genome-wide association
      mapping studies and genomic selection in maize. By contrast, linkage mapping
      studies were until now mostly based on low-density genetic maps and theoretical
      results suggested this to be sufficient. This raises the question, if an increase
      in marker density would be an overkill for linkage mapping in biparental
      populations, or if important QTL mapping parameters would benefit from it. In
      this study, we addressed this question using experimental data and a simulation
      based on linkage maps with marker densities of 1, 2, and 5 cM. QTL mapping was
      performed for six diverse traits in a biparental population with 204 doubled
      haploid maize lines and in a simulation study with varying QTL effects and
      closely linked QTL for different population sizes. Our results showed that high
      density maps neither improved the QTL detection power nor the predictive power
      for the proportion of explained genotypic variance. By contrast, the precision of
      QTL localization, the precision of effect estimates of detected QTL, especially
      for small and medium sized QTL, as well as the power to resolve closely linked
      QTL profited from an increase in marker density from 5 to 1 cM. In conclusion,
      the higher costs for high-density genotyping are compensated for by more precise
      estimates of parameters relevant for knowledge-based breeding, thus making an
      increase in marker density for linkage mapping attractive. 

PMID- 23860724
TI  - Prediction of inclusion body solubilization from shaken to stirred reactors.
AB  - Inclusion bodies (IBs) were solubilized in a u-scale system using shaking
      microtiter plates or a stirred tank reactor in a laboratory setting.
      Characteristic dimensionless numbers for mixing, the Phase number Ph and Reynolds
      number Re did not correlate with the kinetics and equilibrium of protein
      solubilization. The solubilization kinetics was independent of the mixing system,
      stirring or shaking rate, shaking diameter, and energy input. Good agreement was
      observed between the solubilization kinetics and yield on the u-scale and
      laboratory setting. We show that the IB solubilization process is controlled
      predominantly by pore diffusion. Thus, for the process it is sufficient to keep
      the IBs homogeneously suspended, and additional power input will not improve the
      process. The high-throughput system developed on the u-scale can predict
      solubilization in stirred reactors up to a factor of 500 and can therefore be
      used to determine optimal solubilization conditions on laboratory and industrial
      scale.

PMID- 23860725
TI  - Combined preoperative CEA and CD44v6 improves prognostic value in patients with
      stage I and stage II colorectal cancer.
AB  - AIM: Combination of biomarkers may improve diagnosis and have better prognostic
      value than single markers. The purpose of this study was to investigate whether
      combined CEA and CD44v6 improves prognostic value in stage I and stage II (stage
      I/II) colorectal cancer (CRC). METHODS: Preoperative serum CEA level and the
      expression of CD44v6 in CRC tissues were examined by electrochemiluminescence
      immunoassay and immunohistochemistry, respectively. The association of CEA and
      CD44v6 with clinicopathological features and their possible prognostic values was
      analyzed. RESULTS: The preoperative elevated serum CEA level and positive CD44v6
      expression were detected in 30.1 % (52/173) serum samples and 60.5 % (101/167)
      CRC tissues, respectively. Patients with an elevated-CEA level or a CD44v6
      negative tumor had a worse disease-specific survival (DSS) than those with a
      normal-CEA level or CD44v6-positive tumor (P = 0.024, P = 0.012, respectively).
      Moreover, CD44v6 expression could be used in discriminating patients from good to
      poor prognosis in normal-CEA subgroup (P = 0.043), but not in elevated-CEA
      subgroup (P = 0.563). Multivariate analysis revealed that combined CEA and CD44v6
      was an independent prognostic factor for patients with stage I/II CRC (P =
      0.023). However, serum CEA level only retained a borderline significance for
      correlation with a worse DSS (P = 0.059), and CD44v6 expression alone was not an
      independent prognostic factor for DSS in multivariate analysis (P = 0.123).
      CONCLUSION: These results suggested that combined CEA/CD44v6 had better
      prognostic value than CEA or CD44v6 alone for patients with stage I/II CRC.

PMID- 23860726
TI  - Changes in the immune cell population and cell proliferation in peripheral blood
      after gemcitabine-based chemotherapy for pancreatic cancer.
AB  - PURPOSE: Regulatory T cells (Tregs) play a role in the immunosuppressive state in
      pancreatic cancer patients. We aimed to evaluate the changes of immune cells
      population including Tregs caused by gemcitabine (GEM)-based chemotherapy.
      METHODS: Fifty-three patients with pancreatic cancer were enrolled in this study,
      of which 32 received GEM- based chemotherapy. Blood samples were collected before
      and at least 2 weeks after the last dose of chemotherapy. The peripheral blood
      mononuclear cells (PBMCs) were subjected to flow cytometry analysis after
      labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Other lymphocytes
      and NK cell markers were also measured. The proliferative capacity of PBMCs
      stimulated with anti-CD3 was analyzed using H(3) thymidine. RESULTS: The
      percentage and number of Tregs were significantly decreased after chemotherapy (p
      = 0.032, p = 0.003, respectively). The other immune cells and the proliferative
      capacity did not change. CONCLUSION: This study showed that GEM-based
      chemotherapy produced an immunomodulatory effect via the depletion of Tregs.

PMID- 23860727
TI  - Can mu-opioid receptor A118G gene polymorphism be predictive of acute poisoning
      severity in the emergency department?

PMID- 23860728
TI  - On the role of genetic testing for personalized drug overdose management.

PMID- 23860729
TI  - The interactions of methyl tert-butyl ether on high silica zeolites: a combined
      experimental and computational study.
AB  - In this work, the interactions of methyl tert-butyl ether (MTBE) on different
      dealuminated high silica zeolites were studied by means of both experimental and
      computational approaches. Zeolites with different textural and surface features
      were selected as adsorbents and the effect of their physico-chemical properties
      (i.e. pore size architecture and type and amount of surface OH sites) on sorption
      capacity were studied. High silica mordenite (MOR) and Y zeolites (both with a
      SiO2/Al2O3 ratio of 200) and ZSM-5 solid (SiO2/Al2O3 ratio of 500) were selected
      as model sorbents. By combining FTIR and SS-NMR (both (1)H and (13)C CPMAS NMR)
      spectroscopy it was possible to follow accurately the MTBE adsorption process on
      highly defective MOR characterized by a high concentration of surface SiOH
      groups. The adsorption process is found to occur in different steps and to
      involve isolated silanol sites, weakly interacting silanols, and the siloxane
      network of the zeolite, respectively. H-bonding and van der Waals interactions
      occurring between the mordenite surface and MTBE molecules were modeled by DFT
      calculations using a large cluster of the MOR structure where two adjacent side
      pockets were fused in a large micropore to simulate a dealumination process
      leading to silanol groups. This is the locus where MTBE molecules are more
      strongly bound and stabilized. FTIR spectroscopy and gravimetric measurements
      allowed determination of the interaction strength and sorption capacities of all
      three zeolites. In the case of both Y and MOR zeolites, medium-weak H-bonding
      with isolated silanols (both on internal and external zeolite surfaces) and van
      der Waals interactions are responsible for MTBE adsorption, whereas ZSM-5, in
      which a negligible amount of surface silanol species is present, displays a much
      lower amount of adsorbed MTBE retained mainly through van der Waals interactions
      with zeolite siloxane network. 

PMID- 23860730
TI  - Dialkylcyanamides are more reactive substrates toward metal-mediated nucleophilic
      addition than alkylcyanides.
AB  - The dialkylcyanamide complexes Q[PtCl3(NCNR2)] (Q = Ph3PCH2Ph, R2 = Me21, Et22,
      C5H103, C4H8O 4; Q = NMe4, R2 = Me25; Q = NEt4, R2 = Me26) were synthesized
      either by dissolving Q2[Pt2(MU-Cl)2Cl4] in neat NCNR2 (1-4) or by substitution of
      a NCNR2 ligand with Cl(-) in [PtCl2(NCNR2)2] by its treatment with QCl (5, 6).
      Nucleophilic addition of dibenzylhydroxylamine, HON(CH2Ph)2, to 1-6 results in
      the formation of the complexes Q[PtCl3{NHC(NR2)ON(CH2Ph)2}] (Q = Ph3PCH2Ph, R2 =
      Me2, 7; Et2, 8; C5H10, 9; C4H8O, 10; Q = Me4N, R2 = Me211; Q = Et4N, R2 = Me2,
      12) that further convert at room temperature in the solid state (1-24 h) or in a
      solution (0.5-2 h) to the imine complexes Q[PtCl3{N(CH2Ph)=C(H)Ph}] (Q =
      Ph3PCH2Ph, 13; Me4N, 14; Et4N, 15) and the corresponding dialkylureas
      H2NC(=O)NR2. The competitive reactivity study of the nucleophilic addition of
      HON(CH2Ph)2 to (Ph3PCH2Ph)[PtCl3(NCR')] (R' = Ph, NR2, CH2Ph) indicated that the
      reactivity of the coordinated NCNR2 is comparable to NCPh, while NCCH2Ph appeared
      to be much less reactive than the former two ligands. Compounds 1-6 and 13 were
      fully characterized by elemental analyses (C, H, N), high resolution ESI-MS, IR,
      and (1)H and (13)C{(1)H} NMR spectroscopy. The structure of 1 was additionally
      verified by a single-crystal X-ray diffraction.

PMID- 23860731
TI  - Bifunctional polypyridyl-Ru(II) complex grafted onto gadolinium-based
      nanoparticles for MR-imaging and photodynamic therapy.
AB  - The synthesis, optical properties and efficiency of new multifunctional
      nanoparticles as theranostic (fluorescence/MRI/PDT) agents are described. They
      are based on a polysiloxane network and surrounded by gadolinium(III) chelates
      and ruthenium(II) complexes. The size of the nanoparticles is maintained under 5
      nm in order to permit their efficient elimination from the body. Their potential
      use as a theranostic agent (PDT/MRI) is described. The magnetic properties of the
      nanoparticles are studied by relaxometry (r1 = 9.21 mM(-1) s(-1) at 40 MHz; r2/r1
      = 1.14) and the signal enhancement is validated by the acquisition of phantoms on
      a 3 T MRI imager. The therapeutic potential for photodynamic therapy of the
      nanoparticles has been studied in vitro on HEK293 cells and an effective quantum
      yield of 0.33 for (1)O2 production has been determined in deuterated water.

PMID- 23860732
TI  - Quantification of ions with identical mass-to-charge (m/z) ratios by velocity-map
      imaging mass spectrometry.
AB  - By integrating a velocity-map imaging lens and position sensitive detector into
      an electron-impact time-of-flight mass spectrometer, it becomes possible to
      record ion kinetic energy release (KER) distributions for each fragment ion
      alongside the time-of-flight mass spectrum. The KER distributions allow ions of
      identical mass-to-charge ratio to be distinguished and quantified. 

PMID- 23860733
TI  - Fine tuning and orientation control of surface Cu complexes on TiO2(110)
      premodified with mercapto compounds: the effect of different mercapto group
      positions.
AB  - Three-dimensional structures of vacuum-deposited Cu species formed on TiO2(110)
      surfaces premodified with three mercaptobenzoic acid (MBA) isomers were studied
      using polarization-dependent total reflection fluorescence X-ray absorption fine
      structure (PTRF-XAFS). We explored the possibility of fine tuning and orientation
      control of the surface Cu structures, including their coordination and
      configuration against the surface, according to the different mercapto group
      positions of the three MBA isomers (o-, m-, and p-MBA). Almost linear S-Cu-O
      (lattice O of TiO2) surface compounds were formed on the three MBA-modified
      TiO2(110) surfaces; however, the orientation of the Cu species on the o- and m
      MBA-modified TiO2(110) surfaces (40-45 degrees  inclined from the surface normal)
      was different from that on the p-MBA-modified TiO2(110) surface (60 degrees  from
      the surface normal). This work suggests that the selection of a different MBA
      isomer for premodification of a single crystal TiO2(110) surface enables fine
      tuning and orientation control of surface Cu complexes. 

PMID- 23860734
TI  - The influence of shell thickness of Au@TiO2 core-shell nanoparticles on the
      plasmonic enhancement effect in dye-sensitized solar cells.
AB  - Plasmonic core-shell nanoparticles (PCSNPs) can function as nanoantennas and
      improve the efficiency of dye-sensitized solar cells (DSSCs). To achieve maximum
      enhancement, the morphology of PCSNPs needs to be optimized. Here we precisely
      control the morphology of Au@TiO2 PCSNPs and systematically study its influence
      on the plasmonic enhancement effect. The enhancement mechanism was found to vary
      with the thickness of the TiO2 shell. PCSNPs with a thinner shell mainly enhance
      the current, whereas particles with a thicker shell improve the voltage. While
      pronounced plasmonic enhancement was found in the near infrared regime,
      wavelength-independent enhancement in the visible range was observed and
      attributed to the plasmonic heating effect. Emission lifetime measurement
      confirms that N719 molecules neighboring nanoparticles with TiO2 shells exhibit a
      longer lifetime than those in contact with metal cores. Overall, PCSNPs with a 5
      nm shell give the highest efficiency enhancement of 23%. Our work provides a new
      synthesis route for well-controlled Au@TiO2 core-shell nanoparticles and gains
      insight into the plasmonic enhancement in DSSCs. 

PMID- 23860735
TI  - Genetic variation near interleukin 28B and the risk of hepatocellular carcinoma
      in patients with chronic hepatitis C.
AB  - BACKGROUND: We aimed to clarify the association between single nucleotide
      polymorphism (SNP) located near interleukin 28B and hepatocellular carcinoma
      (HCC). METHODS: A cohort comprising 792 patients treated with interferon for
      chronic hepatitis C was investigated. SNPs at rs8099917 and rs12979860 were
      determined. Cumulative incidence and HCC risk were analyzed by Kaplan-Meier and
      Cox proportional hazard analyses for a mean follow-up period of 4.9 years.
      Fibrosis progression rate (FPR) was determined in these patients with a known
      time of infection (n = 294). RESULTS: Cumulative HCC incidence was significantly
      higher in rs8099917 nonTT (minor homozygote or heterozygote) patients than in
      rs8099917 TT (major homozygote) patients (20.8 vs. 10.5% over 10 years, logrank
      test, p = 0.002). This difference was notable in patients infected with genotype
      1 and those treated with pegylated interferon and ribavirin. Among nonSVRs,
      interferon had a limited effect in suppressing alanine aminotransferase (ALT)
      and/or alpha-fetoprotein (AFP) levels in nonTT patients. The suppression of these
      values after interferon therapy was associated with a lower incidence of HCC. FPR
      were similar in TT and nonTT patients. CONCLUSIONS: rs8099917 nonTT is related to
      higher HCC development in patients with HCV genotype 1 and those treated with
      pegylated interferon and ribavirin. Higher HCC incidence observed in nonTT
      patients partly results from the limited suppression of ALT and/or AFP by
      interferon in these patients.

PMID- 23860736
TI  - Persistence of physical activity in middle age: a nonlinear dynamic panel
      approach.
AB  - No prior investigation has considered the effects of state dependence and
      unobserved heterogeneity on the relationship between regular physical activity
      (RPA) and latent health stock (LHS). Accounting for state dependence corrects the
      possible overestimation of the impact of socioeconomic factors. We estimated the
      degree of the state dependence of RPA and LHS among middle-aged Japanese workers.
      The 5 years' longitudinal data used in this study were taken from the
      Longitudinal Survey of Middle and Elderly Persons. Individual heterogeneity was
      found for both RPA and LHS, and the dynamic random-effects probit model provided
      the best specification. A smoking habit, low educational attainment, longer work
      hours, and longer commuting time had negative effects on RPA participation. RPA
      had positive effects on LHS, taking into consideration the possibility of
      confounding with other lifestyle variables. The degree of state dependence of LHS
      was positive and significant. Increasing the intensity of RPA had positive
      effects on LHS and caused individuals with RPA to exhibit greater persistence of
      LHS compared to individuals without RPA. This result implies that policy
      interventions that promote RPA, such as smoking cessation, have lasting
      consequences. We concluded that smoking cessation is an important health policy
      to increase both the participation in RPA and LHS. 

PMID- 23860737
TI  - Correlation between radioactivity levels and heavy metal content in the soils of
      the North Kosovska Mitrovica environment.
AB  - This paper reports the results of radioactivity concentrations and heavy metal
      content in soil samples collected from non-agricultural areas in the municipality
      and vicinity of North Kosovska Mitrovica, formerly the most important mining area
      in Europe. The estimated average activity concentrations of (226)Ra, (232)Th,
      (40)K and (137)Cs are 40.6 +/- 19, 48 +/- 25.4, 743.2 +/- 200.5 and 81 +/- 119 Bq
      kg(-1), respectively. The estimated average absorbed dose rate in the air and the
      annual effective dose are 78.7 nGy h(-1) and 96.6 MUSv, respectively. The radium
      equivalent activity and external hazard index were also calculated. High contents
      of Pb, Zn, Cu, Cd, As and Ni were found in the analyzed soil samples, thus
      indicating pollution of the environment. Most metals have a wide range of values
      spanning 2 to 3 orders of magnitude, which is particularly evident for Pb and Zn.
      Correlations between the activity concentrations of the radionuclides, the heavy
      metal content in soil and the basic soil properties were determined by means of
      the Pearson linear coefficient. Strong positive correlations between the
      naturally occurring radionuclides, and also among Pb, Zn, Cu and Cd were found. 

PMID- 23860738
TI  - Positron emission tomography based in-vivo imaging of early phase stem cell
      retention after intramyocardial delivery in the mouse model.
AB  - PURPOSE: To establish PET as a tool for in-vivo quantification and monitoring of
      intramyocardially transplanted stem cells after labelling with FDG in mice with
      induced myocardial infarction. METHODS: After inducing myocardial infarction in
      C57BL/6 mice, murine embryonic stem cells were labelled with FDG and transplanted
      into the border zone of the infarction. Dynamic PET scans were acquired from 25
      to 120 min after transplantation, followed by a scan with 20 MBq FDG administered
      intravenously for anatomical landmarking. All images were reconstructed using the
      OSEM 3D and MAP reconstruction algorithms. FDG data were corrected for cellular
      tracer efflux and used as marker for cellular retention. FACS analysis of
      transplanted cells expressing enhanced green fluorescent protein was performed to
      validate the PET data. RESULTS: We observed a rapid loss of cells from the site
      of transplantation, followed by stable retention over 120 min. Amounts of
      retention were 5.3 +/- 1.1 % at 25 min, 5.0 +/- 0.9 % at 60 min and 5.7 +/- 1.2 %
      at 120 min. FACS analysis showed a high correlation without significant
      differences between the groups (P > 0.05). FDG labelling did not have any adverse
      effects on cell proliferation or differentiation. CONCLUSION: Up-to-date imaging
      is a powerful method for tracking and quantifying intramyocardially transplanted
      stem cells in vivo in the mouse model. This revealed a massive cell loss within
      minutes, and thereafter a relatively stable amount of about 5 % remaining cells
      was observed. Our method may become crucial for further optimization of cardiac
      cell therapy in the widely used mouse model of infarction.

PMID- 23860739
TI  - A large retrospective single-centre study to define the best image acquisition
      protocols and interpretation criteria for white blood cell scintigraphy with
      99mTc-HMPAO-labelled leucocytes in musculoskeletal infections.
AB  - PURPOSE: The diagnosis of infection is often based on clinical, pathological and
      microbiological results. However, these investigations lack specificity. White
      blood cell (WBC) scintigraphy is considered the gold standard nuclear imaging
      technique for diagnosing infections in bone and soft tissues (except
      spondylodiscitis). However, image acquisition and interpretation criteria differ
      amongst centres throughout the world, leading to differences in reported results.
      The aim of this study was to identify the most accurate WBC scintigraphy
      acquisition and interpretation protocols for diagnosis of bone and soft tissue
      infections. METHODS: Included in this retrospective study were 297 patients with
      suspected bone or soft tissue infection who underwent WBC scintigraphy with
      (99m)Tc-HMPAO-labelled leucocytes between 2009 and 2012. Sensitivity,
      specificity, accuracy, and positive and negative predictive values of WBC
      scintigraphy were determined for two different dual time point acquisition
      protocols (fixed-time acquisition and time decay-corrected acquisition) and five
      image interpretation methods (visual and semiquantitative with four different
      reference regions of interest). Final diagnosis was based on pathological and
      microbiological reports, and when these were not available, on clinical follow-up
      of at least 6 months. RESULTS: The best acquisition protocol was 4 h and 20 - 24
      h dual time-point acquisition with time decay-corrected acquisition. When using
      this acquisition protocol, visual qualitative interpretation led to a sensitivity
      of 85.1 %, a specificity of 97.1 %, a diagnostic accuracy of 94.5 %, a positive
      predictive value of 88.8 % and a negative predictive value of 95.9 %. For
      semiquantitative analysis, the best results were found when lesion-to-reference
      ratios were calculated with the contralateral side as the reference tissue,
      except for osteomyelitis and infected osteosynthesis, for which the contralateral
      bone marrow was found to be the best reference tissue. Results of the
      semiquantitative analyses per se were not better than for visual analysis. In the
      optimal analysis protocol, scans are first visually evaluated, and if this gives
      equivocal results, semiquantitative analysis is performed. This strategy resulted
      in an improved sensitivity of 97.9 %, a specificity of 91.8 % and a diagnostic
      accuracy of 93.1 %. CONCLUSION: WBC scintigraphy for bone and soft-tissue
      infection is best performed using a dual acquisition protocol at 4 h and at 20-24
      h after injection, in which the acquisition time of the scans is corrected for
      decay. In most patients, visual analysis is sufficient and leads to high
      diagnostic accuracy. When interpretation by visual analysis is inconclusive,
      semiquantitative analysis adds accuracy. Based on our results, we propose a flow
      chart for analysing WBC scintigraphy in musculoskeletal infections.

PMID- 23860740
TI  - Three dimensions of oppositionality in autism spectrum disorder.
AB  - In autism spectrum disorder (ASD), symptoms of oppositional defiant disorder
      (ODD) are common but poorly understood. DSM-5 has adopted a tripartite model of
      ODD, parsing its features into 'angry and irritable symptoms' (AIS),
      'argumentative and defiant behavior' (ADB) and 'vindictiveness'. This was based
      on findings in non-autistic populations that each of these dimensions of
      oppositionality has a distinct constellation of associations with internalising
      and externalising psychopathology. We applied the tripartite DSM-5 ODD model to
      ASD to test its generalisability beyond non-ASD populations; and to elucidate the
      nature of ODD symptoms in ASD. Participants were 216 verbally-fluent young people
      (mean age = 9.6 years, range 3.0 to 16.2 years, 82 % male) with ASD. Cross
      sectional parent-and teacher-report data were analysed using bootstrap multiple
      regression to test the following predictions, derived from studies of non-ASD
      young people: (1) AIS will be the main predictor of internalising problems; (2)
      ADB will be the main predictor of ADHD symptoms; (3) all ODD traits will
      independently predict conduct disorder symptoms; (4) vindictiveness will be the
      main predictor of aggressive conduct problems. Our findings using both parent and
      teacher data were consistent with the non-ASD ODD literature. AIS were associated
      with internalising but not externalising problems; ADB and vindictiveness were
      associated with externalising but not internalising problems; and vindictiveness
      was the main predictor of aggression. The DSM-5 tripartite model of ODD appears
      to be generalisable to ASD: for people with an autistic disorder, AIS, ADB and
      vindictive dimensions of oppositionality have distinct associations with
      concurrent psychopathology, suggesting the need to assess them as separate
      constructs.

PMID- 23860741
TI  - The ratio of ICRP103 to ICRP60 calculated effective doses from CT: Monte Carlo
      calculations with the ADELAIDE voxel paediatric model and comparisons with
      published values.
AB  - The ADELAIDE voxel model of paediatric anatomy was used with the EGSnrc Monte
      Carlo code to compare effective dose from computed tomography (CT) calculated
      with both the ICRP103 and ICRP60 definitions which are different in their tissue
      weighting factors and in the included tissues. The new tissue weighting factors
      resulted in a lower effective dose for pelvis CT (than if calculated using ICRP60
      tissue weighting factors), by 6.5% but higher effective doses for all other
      examinations. ICRP103 calculated effective dose for CT abdomen + pelvis was
      higher by 4.6%, for CT abdomen (by 9.5%), for CT chest + abdomen + pelvis (by
      6%), for CT chest + abdomen (by 9.6%), for CT chest (by 10.1%) and for cardiac CT
      (by 11.5%). These values, along with published values of effective dose from CT
      that were calculated for both sets of tissue weighting factors were used to
      determine single values for the ratio ICRP103:ICRP60 calculated effective doses
      from CT, for seven CT examinations. The following values for ICRP103:ICRP60 are
      suggested for use to convert ICRP60 calculated effective dose to ICRP103
      calculated effective dose for the following CT examinations: Pelvis CT, 0.75; for
      abdomen CT, abdomen + pelvis CT, chest + abdomen + pelvis CT, 1.00; for chest +
      abdomen CT, and for chest CT. 1.15; for cardiac CT 1.25.

PMID- 23860742
TI  - Characterization of primary human skeletal muscle cells from multiple commercial
      sources.
AB  - There is a significant unmet need for safe, anabolic muscle therapies to treat
      diseases and conditions associated with severe muscle weakness and frailty. The
      identification of such therapies requires appropriate cell-based screening assays
      to select compounds for further development using animal models. Primary human
      skeletal muscle cells have recently become available from a number of commercial
      vendors. Such cells may be valuable for studying the mechanisms that direct
      muscle differentiation, and for identifying and characterizing novel therapeutic
      approaches for the treatment of age- and injury-induced muscle disorders.
      However, only limited characterization of these cells has been reported to date.
      Therefore, we have examined four primary human muscle cell preparations from
      three different vendors for their capacity to differentiate into multinucleated
      myotubes. Two of the preparations demonstrated robust myotube formation and
      expressed characteristic markers of muscle differentiation. Furthermore, these
      myotubes could be induced to undergo morphological atrophy- and hypertrophy-like
      responses, and atrophy could be blocked with an inhibitor of myostatin signaling,
      a pathway that is known to negatively regulate muscle mass. Finally, the myotubes
      were efficiently infected with recombinant adenovirus, providing a tool for
      genetic modification. Taken together, our results indicate that primary human
      muscle cells can be a useful system for studying muscle differentiation, and may
      also provide tools for studying new therapeutic molecules for the treatment of
      muscle disease. 

PMID- 23860743
TI  - Effects of pH, temperature, and osmolarity on the morphology and survival rate of
      primary hemocyte cultures from the mitten crab, Eriocheir sinensis.
AB  - Hemocytes are the main immune defense cells in crustacean, and its in vitro
      culture can be a useful tool for the study of host and pathogen interaction. In
      the present study, the primary hemocyte culture of Chinese mitten crab (Eriocheir
      sinensis), including mixed and single hemocyte, was set up for the first time. In
      this study, different pH (6.4, 6.8, 7.2, 7.6, and 8.0), temperature (26, 28, and
      30 degrees C), and osmolarity (500, 700, 900, 1,100, and 1,300 mOsm kg(-1))
      values were tested. Moreover, the effects of two types of medium (1* L-15 and 3*
      L-15) with the same osmolarity on hemocyte culture were evaluated. After
      incubation at different culture conditions, the morphological changes
      (degranulation, lysis, shrinkage, and detachment) and survival rate of hemocytes
      were taken into account in order to evaluate the culture condition effect. Our
      results showed that the total hemocyte counts of Chinese mitten crab were about
      2.5 * 10(7) cells ml(-1), and three subpopulations of hemocytes were
      distinguished as granulocytes (43.46 +/- 4.98%), semigranulocytes (31.04 +/-
      1.95%), and hyalinocytes (25.50 +/- 4.89%). The optimal culture condition for
      primary hemocytes of Chinese mitten crab was 3* L-15 medium, 1,100 mOsm kg(-1),
      pH 6.8 at 28 degrees C. Hemocytes at optimal culture condition could retain a
      better morphology and higher survival rate: hemocytes retained a survival rate
      >60% after 5 d and >40% after 7 d. Furthermore, the hemocyte subpopulations were
      isolated by Percoll step gradient centrifugation and cultured in optimized
      hemocyte culture conditions. The results showed that hyalinocytes and
      semigranulocytes could maintain a survival rate of >50% after 15 d, while
      granulocytes only retained a survival rate of 26% after 5 d.

PMID- 23860744
TI  - Social relationships and quality of life moderate distress associated with
      delusional ideation.
AB  - PURPOSE: In a previous study, individuals who followed a particular new religious
      movement (NRM) reported significantly less distress even though they reported
      similar levels of delusional ideation when compared with individuals diagnosed
      with psychotic disorders. Protective factors such as social relationship quality
      and quality of life (QOL) were hypothesized to explain attenuated distress
      associated with delusional ideation. METHODS: NRM individuals (n = 29),
      individuals diagnosed with psychotic disorders (n = 25), and control individuals
      (n = 63) were recruited. Psychotic symptoms, delusion-proneness, and facets of
      social relationships quality and QOL were examined across group. Potential
      moderators of the relationship between group membership and distress were further
      examined in multiple regression models. RESULTS: NRM participants reported more
      social relationships that were of higher quality (as demonstrated by more crisis
      supports, unique and overlap supports, more helpful supports and more
      reciprocated supports) than individuals with psychotic disorders. NRM
      participants also reported significantly higher QOL than individuals with
      psychotic disorders. Furthermore, NRM participants reported more distinct and
      less reciprocated supports, and significantly higher psychological,
      environmental, and total QOL, when compared with control participants. The
      relationship between group membership, delusional ideation, and distress was
      moderated by relationship reciprocity as well as by total QOL. CONCLUSIONS:
      Findings highlight the importance of establishing healthy reciprocal social
      relationships and improving QOL in people diagnosed with psychotic disorders, as
      these factors may act as a buffer against distress associated with delusional
      beliefs.

PMID- 23860745
TI  - Quality by design approach for viral clearance by protein a chromatography.
AB  - Protein A chromatography is widely used as a capture step in monoclonal antibody
      (mAb) purification processes. Antibodies and Fc fusion proteins can be
      efficiently purified from the majority of other complex components in harvested
      cell culture fluid (HCCF). Protein A chromatography is also capable of removing
      modest levels of viruses and is often validated for viral clearance. Historical
      data mining of Genentech and FDA/CDER databases systematically evaluated the
      removal of model viruses by Protein A chromatography. First, we found that for
      each model virus, removal by Protein A chromatography varies significantly across
      mAbs, while remains consistent within a specific mAb product, even across the
      acceptable ranges of the process parameters. In addition, our analysis revealed a
      correlation between retrovirus and parvovirus removal, with retrovirus data
      generally possessing a greater clearance factor. Finally, we describe a
      multivariate approach used to evaluate process parameter impacts on viral
      clearance, based on the levels of retrovirus-like particles (RVLP) present among
      process characterization study samples. It was shown that RVLP removal by Protein
      A is robust, that is, parameter effects were not observed across the ranges
      tested. Robustness of RVLP removal by Protein A also correlates with that for
      other model viruses such as X-MuLV, MMV, and SV40. The data supports that
      evaluating RVLP removal using process characterization study samples can
      establish multivariate acceptable ranges for virus removal by the protein A step
      for QbD. By measuring RVLP instead of a model retrovirus, it may alleviate some
      of the technical and economic challenges associated with performing large, design
      of-experiment (DoE)-type virus spiking studies. This approach could also serve to
      provide useful insight when designing strategies to ensure viral safety in the
      manufacturing of a biopharmaceutical product.

PMID- 23860746
TI  - Supramolecular BODIPY-Zn(II)-bisporphyrin dyad and trinitrofluorenone
      encapsulated triad as models of antenna-reaction center: synthesis, structure and
      photophysical properties.
AB  - We describe the synthesis, characterization and photophysical properties of the
      dyads Zn2DEP.TNF (1) and Zn2DEP.2Py-BDP (2) and triad Zn2DEP.2Py-BDP.TNF (3),
      which enable us to investigate the changes in the spectroscopic properties upon
      the axial coordination of pyridine substituted bodipy (Py-BDP) to Zn2DEP in the
      dyads and the further encapsulation of TNF in the triad. Zn2DEP.TNF (1) is
      structurally characterized while the other compounds, Py-BDP, 2 and 3, are
      geometrically optimized using DFT in the absence of X-ray crystallography. It has
      been found that the encapsulated TNF guest within the bisporphyrin cavity is
      involved in strong pi-pi interactions with the host resulting in robust host
      guest assemblies that also retain the structural integrity in solution for a long
      time. The association constants, K, between the host and guests are calculated at
      298 K by measuring the change in the fluorescence emission in solution and are
      found to be 1.0 * 10(7) M(-2) for the 1 : 2 binding in 2 and 1.2 * 10(3) M(-1)
      for the 1 : 1 binding in 3. The solution (1)H NMR spectrum of the supramolecular
      dyad 2 shows an upfield shift of the Py-BDP protons due to the strong ring
      current of the porphyrin rings. Similarly, upon the encapsulation of TNF in triad
      3, the guest protons undergo an upfield shift owing to the ring current effect.
      Electrochemical studies of dyad 2 indicate that the Py-BDP and Zn-bisporphyrin
      subunits in the dyads interact very weakly. The negative and positive shifts of
      the reduction and oxidation potentials indicate that it is difficult to
      reduce/oxidize the encapsulated complex 3. The steady state emission spectrum
      shows that the fluorescence intensity of the axially coordinated Py-BDP in 2
      (excited at 500 nm) is remarkably quenched in comparison to free Py-BDP due to
      efficient photoinduced intramolecular singlet-to-singlet energy transfer from the
      excited state of Py-BDP to the zinc-bisporphyrin in 2. The remarkable quenching
      of the fluorescence intensity of Py-BDP upon excitation at 500 nm in 3 is due to
      photoinduced electron transfer from the excited states of Py-BDP to TNF, which is
      also thermodynamically favorable. The location of the electron densities on the
      HOMO and LUMO further support the formation of a charge-separated state in which
      the zinc-bisporphyrin acts as an electron donor whilst TNF acts as an electron
      acceptor in the supramolecular triad 3. The electrochemically evaluated HOMO-LUMO
      gap also maintains a good agreement with the computed HOMO-LUMO gap. 

PMID- 23860747
TI  - Immunization in practice - clearing the cobwebs: correspondence.

PMID- 23860748
TI  - Immunization in practice - clearing the cobwebs: author's reply.

PMID- 23860749
TI  - To assess the changes of tracheal cuff pressure after a calibrating orogastric
      tube insertion.
AB  - Insertion of a medical instrument into the esophagus may affect tracheal tube
      pressure. This study evaluated the potential effect of a calibrating orogastric
      tube insertion on tracheal cuff pressure in patients undergoing laparoscopic
      bariatric surgery. Adult patients who were scheduled for elective bariatric
      surgery requiring insertion of a calibrating orogastric tube were assessed for
      eligibility for this study. After successful tracheal intubation, the tracheal
      tube with a high-volume, low-pressure cuff was adjusted to range from 25 to 30
      cmH2O using a manometer. Tracheal cuff pressure was monitored continuously while
      the calibrating orogastric tube was being advanced. The change of tracheal cuff
      pressure was recorded after the calibrating orogastric tube had been left in situ
      for 3 min. After insertion of the calibrating orogastric tube, the median
      tracheal cuff pressure increased from 28 [27-28 (25-30)] to 36 [30-42 (26-64)]
      cmH2O (P < 0.001) and was greater than 35 cmH2O in 30 of 60 patients (50 %). Our
      results suggest that the tracheal cuff pressure should be routinely monitored in
      patients undergoing laparoscopic bariatric surgery requiring insertion of a
      calibrating orogastric tube.

PMID- 23860750
TI  - A genome-wide supported variant in CACNA1C influences hippocampal activation
      during episodic memory encoding and retrieval.
AB  - The alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene
      is one of the best replicated susceptibility loci for bipolar disorder,
      schizophrenia and major depression. It is involved in learning, memory and brain
      plasticity. Genetic studies using functional magnetic resonance imaging (fMRI)
      reported evidence of association with the CACNA1C single nucleotide polymorphism
      rs1006737 with functional correlates of episodic memory encoding and retrieval,
      especially activations in the hippocampus. These results, however, are
      inconsistent with regard to the magnitude and directionality of effect. In the
      present study, brain activation was measured with fMRI during an episodic memory
      encoding and retrieval task using neutral faces in two independent samples of 94
      and 111 healthy subjects, respectively. Within whole brain analyses, a main
      effect of genotype emerged mainly in the right hippocampus during encoding as
      well as retrieval within the first sample: Carriers of the minor allele (A)
      exhibited lower activations compared to G/G allele carriers. This effect could be
      replicated within the second sample, however, only for the retrieval condition.
      The results strengthen findings that rs1006737 is associated with neural systems
      related to memory processes in hippocampal regions which are detectable in
      healthy subjects. 

PMID- 23860751
TI  - Symmetry of the pupillary light reflex and its relationship to retinal nerve
      fiber layer thickness and visual field defect.
AB  - PURPOSE: To assess the relationship between the pupillary light reflex (PLR) and
      visual field (VF) mean deviation (MD) and retinal nerve fiber layer (RNFL)
      thickness. METHODS: A total of 148 patients with glaucoma (mean age 67 +/- 11,
      49% female) and 71 controls (mean age 60 +/- 10, 69% female) were included in
      this study. Using a pupillometer, we recorded and analyzed pupillary responses at
      varied stimulus patterns (full field, superonasal and inferonasal quadrant arcs).
      We compared the responses between the two eyes, compared responses to stimuli in
      the superonasal and inferonasal fields within each eye, and calculated the
      absolute PLR value of each individual eye. We assessed the relationship among
      PLR, MD, and RNFL thickness using the Pearson correlation coefficient. For
      analyses performed at the level of individual eyes, we used multilevel modeling
      to account for between-eye correlations within individuals. RESULTS: For every
      0.3 log unit difference in between-eye asymmetry of PLR, there was an average 2.6
      dB difference in visual field MD (correlation coefficient R = 0.83, P < 0.001)
      and a 3.2-MUm difference in RNFL thickness between the two eyes (R = 0.67, P <
      0.001). Greater VF damage and thinner RNFL for each individual eye were
      associated with smaller response amplitude, slower velocity, and longer time to
      peak constriction and dilation after adjusting for age and sex (all P < 0.001).
      However, within-eye asymmetry of PLR between superonasal and inferonasal
      stimulation was not associated with corresponding within-eye differences in VF or
      RNFL. CONCLUSIONS: As measured by this particular device, the PLR is strongly
      correlated with VF functional testing and measurements of RNFL thickness.

PMID- 23860752
TI  - In vivo morphology of the limbal palisades of vogt correlates with progressive
      stem cell deficiency in aniridia-related keratopathy.
AB  - PURPOSE: To investigate morphologic alterations in the limbal palisades of Vogt
      in a progressive form of limbal stem cell deficiency. METHODS: Twenty Norwegian
      subjects (40 eyes) with congenital aniridia and 9 healthy family members (18
      eyes) without aniridia were examined. Clinical grade of aniridia-related
      keratopathy (ARK) was assessed by slit-lamp biomicroscopy, and tear production
      and quality, corneal thickness, and sensitivity were additionally measured. The
      superior and inferior limbal palisades of Vogt and central cornea were examined
      by laser scanning in vivo confocal microscopy (IVCM). RESULTS: In an aniridia
      patient with grade 0 ARK, a transparent cornea and normal limbal palisade
      morphology were found. In grade 1 ARK, 5 of 12 eyes had degraded palisade
      structures. In the remaining grade 1 eyes and in all 20 eyes with stage 2, 3, and
      4 ARK, palisade structures were absent by IVCM. Increasing ARK grade
      significantly correlated with reduced visual acuity and corneal sensitivity,
      increased corneal thickness, degree of degradation of superior and inferior
      palisade structures, reduced peripheral nerves, increased inflammatory cell
      invasion, and reduced density of basal epithelial cells and central subbasal
      nerves. Moreover, limbal basal epithelial cell density and central corneal
      subbasal nerve density were both significantly reduced in aniridia compared to
      healthy corneas (P = 0.002 and 0.003, respectively). CONCLUSIONS: Progression of
      limbal stem cell deficiency in aniridia correlates with degradation of palisade
      structures, gradual transformation of epithelial phenotype, onset of
      inflammation, and a corneal nerve deficit. IVCM can be useful in monitoring early
      to late-stage degenerative changes in stem cell-deficient patients.

PMID- 23860753
TI  - Correlation between reflectivity of subretinal fluid in OCT images and
      concentration of intravitreal VEGF in eyes with diabetic macular edema.
AB  - PURPOSE: The reflectivity of optical coherence tomographic (OCT) images has been
      used to evaluate retinal diseases. The purpose of our study was to determine
      whether a significant correlation exists between the reflectivity of the
      subretinal fluid (SRF) and the concentration of intravitreal cytokines in eyes
      with diabetic macular edema (DME). METHODS: A retrospective comparative study was
      done of eyes with DME with SRF before vitrectomy. The reflectivity of the SRF was
      determined from the OCT images. Vitreous samples were collected during
      vitrectomy, and analyzed for the concentrations of VEGF, IL-6, and IL-8. To
      determine the factors in the SRF that could affect the reflectivity, the aqueous
      humor of isolated swine eyes was replaced by saline with plasma, albumin, or
      fibrinogen, and the reflectivity of the anterior chamber was determined by
      anterior segment OCT. RESULTS: The average OCT reflectivity of the SRF was 3.52
      arbitrary units (AU; 15 eyes; range, 0.01-20.7 AU). The average concentration of
      VEGF was 870.1 pg/mL, that of IL-6 was 131.7 pg/mL, and that of IL-8 was 224.1
      pg/mL. The degree of OCT reflectivity was correlated significantly with the
      intravitreal VEGF concentration (r = 0.516, P = 0.049, Spearman's rank
      correlation coefficient), but not with IL-6 or IL-8. In the swine eyes, the
      presence of plasma, bilirubin, and fibrinogen in the anterior chamber led to
      significant increases in the reflectivity. CONCLUSIONS: The significant
      correlation between the reflectivity of SRF and intravitreal VEGF indicates that
      OCT can be used to monitor the level of VEGF in eyes with DME.

PMID- 23860755
TI  - Population-based assessment of prevalence and risk factors for pterygium in the
      South Indian state of Andhra Pradesh: the Andhra Pradesh Eye Disease Study.
AB  - PURPOSE: To describe the prevalence and risk factors for pterygium in a
      population-based sample of individuals aged 30 years and older in South Indian
      state of Andhra Pradesh. METHODS: A cross-sectional study was conducted in one
      urban and three rural locations in which 10,293 subjects were examined. All the
      subjects underwent comprehensive eye examination and a detailed interview by
      trained professionals. Pterygium was defined as fleshy fibro vascular growth,
      crossing the limbus, and typically seen on the nasal conjunctiva in either eye.
      RESULTS: Data were analyzed for 5586 subjects who were aged 30 years and older at
      the time of participation. The mean age of the participants was 47.5 years (SD 13
      years; range 30-102 years). In total, 46.4% were male, 56.7% had no education,
      52.2% of them were involved in outdoor occupations, and 25% belonged to urban
      area. The prevalence of pterygium was 11.7% (95% confidence interval [CI]: 10.9
      12.6). The multiple logistic regression analysis revealed significantly higher
      odds of pterygium among older age groups, rural residents (odds ratio [OR]: 1.8;
      95% CI: 1.4-2.4; P > 0.01), and those involved in outdoor occupations (OR: 1.8;
      95% CI: 1.5-2.2, P < 0.001). Education had a protective effect (OR: 0.6; 95% CI:
      0.5-0.7; P < 0.001). CONCLUSIONS: Pterygium is common in the South Indian state
      of Andhra Pradesh. Exposure to sunlight is a significant modifiable risk factor.
      Protecting the eyes from sunlight may decrease the risk of pterygium. However,
      the important public health challenge is to encourage the use of this protection
      as a routine in developing countries such as India.

PMID- 23860754
TI  - Substratum compliance modulates corneal fibroblast to myofibroblast
      transformation.
AB  - PURPOSE: The transformation of fibroblasts to myofibroblasts is critical to
      corneal wound healing, stromal haze formation, and scarring. It has recently been
      demonstrated that the provision of biomimetic substratum topographic cues
      inhibits the progression toward the myofibroblast phenotype under the influence
      of transforming growth factor beta1 (TGF-beta1). The objective of this study was
      to determine the effect of another fundamental biophysical cue, substrate
      compliance, on TGF-beta1-induced myofibroblast transformation of primary corneal
      cells isolated from human and rabbit corneas. METHODS: Human and rabbit corneal
      fibroblasts were cultured on surfaces of varying substrate compliance (4-71 kPa)
      and tissue culture plastic (TCP) (> 1 gigapascal [GPa]). Cells were cultured in
      media containing TGF-beta1 at concentrations of 0, 1, or 10 ng/mL for 72 hours.
      RNA and protein were collected from cells cultured on polyacrylamide gels and TCP
      and were analyzed for the expression of alpha-smooth muscle actin (alpha-SMA), a
      key marker of myofibroblast transformation, using quantitative PCR,
      immunocytochemistry, and Western blot. RESULTS: Cells grown on more compliant
      substrates demonstrated significantly reduced amounts of alpha-SMA mRNA compared
      with TCP. Immunocytochemistry and Western blot analysis determining the presence
      of alpha-SMA corroborated this finding, thus confirming a reduced transformation
      to the myofibroblast phenotype on more compliant substrates compared with cells
      on TCP in the presence of TGF-beta1. CONCLUSIONS: These data indicate that
      substrate compliance modulates TGF-beta1-induced expression of alpha-SMA and thus
      influences myofibroblast transformation in the corneal stroma. This provides
      further evidence that biomimetic biophysical cues inhibit myofibroblast
      transformation and participate in stabilizing the native cellular phenotype.

PMID- 23860756
TI  - Clinical and immunological characterization of paraneoplastic retinopathy.
AB  - PURPOSE: To report the clinical and immunological characterization of
      paraneoplastic retinopathy (PR) and to investigate the association between
      spectral-domain optical coherence tomography (SDOCT) findings and the targets of
      autoantibodies in PR. METHODS: We retrospectively enrolled eight patients (age
      range, 57-85 years; four men and four women) suspected of having PR. All patients
      underwent comprehensive ophthalmic examinations, including best-corrected visual
      acuity (BCVA) measurement, slitlamp examinations, kinetic visual field testing
      with Goldmann perimetry, electroretinography (ERG), fundus photography,
      fluorescein angiography, fundus autofluorescence (FAF), SDOCT, and serum sample
      tests (Western blot analysis and immunohistochemistry [IHC]). RESULTS: Three
      patients had a history of malignant tumors, and four patients were newly
      diagnosed as having neoplastic tumors (small cell lung carcinoma [SCLC], thymoma,
      pancreatic neuroendocrine neoplasm, and colon cancer). Another de novo malignancy
      (SCLC) was detected in a patient with a history of malignancy (bladder cancer and
      liposarcoma). The BCVA in these patients ranged from hand motion to 1.5. Goldmann
      perimetry revealed island, ring-shaped, concentric, or central scotoma. All
      patients showed nonrecordable or reduced amplitude results on ERG. Fluorescein
      leakage was detected in five patients. Hyperautofluorescence and/or
      hypoautofluorescence on FAF was detected in six patients. The serum sample tests
      identified anti-retinal antibodies in all patients. Patients whose serum
      contained anti-photoreceptor or anti-retinal pigment epithelium antibody on IHC
      showed damage of the outer retina on SDOCT. CONCLUSIONS: In this case series, PR
      was associated with a variety of neoplasms and autoantibodies. Spectral-domain
      OCT can be used to characterize morphologic changes, and the changes were
      associated with the targets of autoantibodies.

PMID- 23860758
TI  - Elevated levels of multiple biomarkers of Alzheimer's disease in the aqueous
      humor of eyes with open-angle glaucoma.
AB  - PURPOSE: To investigate levels of biomarkers of Alzheimer's disease in the
      aqueous humor in patients with open-angle glaucoma (OAG). METHODS: Aqueous humor
      samples were collected from 38 patients with cataracts, 20 patients with POAG,
      and 32 patients with exfoliation glaucoma. Aqueous levels of apolipoprotein (Apo)
      AI, ApoCIII, ApoE, transthyretin (TTR), complement factor H, complement C3, and
      alpha2-macroglobulin (alpha2M) were determined by multiplex bead immunoassay.
      Clinical data were obtained from medical charts. RESULTS: Age and sex did not
      differ significantly among groups. POAG patients had significantly higher aqueous
      levels of Apo AI, ApoCIII, ApoE, TTR, and alpha2M compared with cataract patients
      (P < 0.001, P = 0.036, P < 0.001, P < 0.001, and P < 0.001, respectively).
      Corresponding values for exfoliation glaucoma patients were also significantly
      higher compared with those for cataract patients (P = 0.003, P = 0.009, P <
      0.001, P < 0.001, and P < 0.001), and those levels correlated positively with
      each other in eyes with OAG (P < 0.001 for all combinations). Complement factor H
      and complement C3 levels did not differ among groups. Mean deviation values for
      the Humphrey visual field test correlated positively with levels of Apo AI, ApoE,
      TTR, and complement factor H in OAG patients (P = 0.026, 0.012, 0.008, and 0.027,
      respectively), but age and IOP values were not correlated with protein levels.
      CONCLUSIONS: OAG patients had elevated levels of multiple biomarkers of
      Alzheimer's disease in the aqueous humor.

PMID- 23860757
TI  - Quantitative fundus autofluorescence in healthy eyes.
AB  - PURPOSE: Fundus autofluorescence was quantified (qAF) in subjects with healthy
      retinae using a standardized approach. The objective was to establish normative
      data and identify factors that influence the accumulation of RPE lipofuscin
      and/or modulate the observed AF signal in fundus images. METHODS: AF images were
      acquired from 277 healthy subjects (age range: 5-60 years) by employing a
      Spectralis confocal scanning laser ophthalmoscope (cSLO; 488-nm excitation; 30
      degrees ) equipped with an internal fluorescent reference. For each image, mean
      gray level was calculated as the average of eight preset regions, and was
      calibrated to the reference, zero-laser light, magnification, and optical media
      density from normative data on lens transmission spectra. Relationships between
      qAF and age, sex, race/ethnicity, eye color, refraction/axial length, and smoking
      status were evaluated as was measurement repeatability and the qAF spatial
      distribution. RESULTS: qAF levels exhibited a significant increase with age. qAF
      increased with increasing eccentricity up to 10 degrees  to 15 degrees  from the
      fovea and was highest superotemporally. qAF values were significantly greater in
      females, and, compared with Hispanics, qAF was significantly higher in whites and
      lower in blacks and Asians. No associations with axial length and smoking were
      observed. For two operators, between-session repeatability was +/- 9% and +/-
      12%. Agreement between the operators was +/- 13%. CONCLUSIONS: Normative qAF data
      are a reference tool essential to the interpretation of qAF measurements in
      ocular disease.

PMID- 23860759
TI  - Wide-field laser ophthalmoscopy for mice: a novel evaluation system for
      retinal/choroidal angiogenesis in mice.
AB  - PURPOSE: The purpose of this study was to investigate the application of wide
      field laser ophthalmoscopy (Optos) for the evaluation of established models of
      angiogenesis and the healthy retina in mice. METHODS: To investigate whether
      angiogenesis and leakage in the retina and choroid can be evaluated with Optos,
      we used two models of angiogenesis: oxygen-induced retinopathy (OIR) and laser
      induced choroidal neovascularization (CNV). Fundus imaging and fluorescein
      angiography (FAG) were performed with the Optos system without a contact lens.
      Furthermore, to evaluate in vivo leukocyte infiltration in these models, we
      injected acridine orange (AO) and performed imaging using Optos. RESULTS: In vivo
      fundus imaging with Optos did not require any additional optical device.
      Additionally, Optos enabled us to repeatedly obtain high-resolution color images
      and FAG images in the OIR model as well as in the CNV model in mice. Through a
      combination of Optos imaging and AO fluorography, the number and location of the
      infiltrating leukocytes could be identified in these models. CONCLUSIONS: Optos
      is a wide-viewing imaging tool for the noninvasive in vivo evaluation of common
      angiogenesis models, oxygen-induced retinopathy and laser-induced choroidal
      neovascularization, as well as the healthy retina in mice.

PMID- 23860760
TI  - Familial correlation of retinal vascular caliber in Singapore Chinese.
AB  - PURPOSE: Our study aimed to explore the heritability of retinal vascular caliber
      among Singapore Chinese families. METHODS: In the Strabismus, Amblyopia, and
      Refractive Error Study in Singaporean Chinese Preschoolers (STARS) family study
      conducted from 2008 to 2010, a total of 727 participants (304 parent-child pairs,
      83 sibling pairs, and 87 spouse pairs) were included in the analysis. According
      to standardized protocols, retinal photography, blood pressure measurements,
      anthropometric measurements, and interviews were performed at clinic. Retinal
      vascular caliber was assessed by a computer-assisted imaging program (IVAN).
      Familial correlation of retinal vascular caliber among family pairs was
      calculated by the FCOR procedure with S.A.G.E. computer software program package
      and heritability was double the value of the familial correlation. RESULTS: Mean
      age was 8.59 years in 304 children and 39.90 years in 423 parents. Mean CRAE and
      CRVE were 157.09 and 220.80 MUm in children, and 150.29 and 220.70 MUm in
      parents, respectively. In multivariate analysis, familial correlation of CRVE was
      0.36 (P < 0.001) among parent-child pairs and 0.28 (P < 0.05) among sibling
      pairs, respectively. Heritability of CRVE was 0.72 and 0.56 among parent-child
      pairs and sibling pairs, respectively. Family correlation and heritability of
      CRAE were not significant. CONCLUSIONS: This familial correlation study showed a
      strong correlation of retinal venular caliber in Singapore Chinese families among
      parent-child pairs and sibling pairs, independent of age, sex, blood pressure,
      and BMI. Our findings provide further evidence on substantial heritability of the
      microvasculature.

PMID- 23860761
TI  - Handheld shape discrimination hyperacuity test on a mobile device for remote
      monitoring of visual function in maculopathy.
AB  - PURPOSE: Frequency monitoring of age-related macular degeneration (AMD) and
      diabetic retinopathy (DR) is crucial for timely intervention. This study
      evaluated a handheld shape discrimination hyperacuity (hSDH) test iPhone app
      designed for visual function self-monitoring in patients with AMD and DR.
      METHODS: One hundred subjects (27 visually normal, 37 with AMD, and 36 with DR)
      were included based on clinical documentation and visual acuity of 20/100 or
      better. The hSDH test was implemented on the iOS platform. A cross-sectional
      study was conducted to compare the hSDH test with a previously established
      desktop SDH (dSDH) test and to assess the effect of disease severity on the hSDH
      test. A user survey was also conducted to assess the usability of the hSDH test
      on the mobile device. RESULTS: The hSDH test and dSDH test were highly correlated
      (r = 0.88, P < 0.0001). Bland-Altman analysis indicated no significant difference
      in hSDH and dSDH measurements. One-way ANOVA indicated that the mean hSDH
      measurement of the eyes with advanced AMD (n = 16) or with severe to very severe
      nonproliferative DR (NPDR) (n = 12) was significantly worse than that of the eyes
      with intermediate AMD (n = 11) or with mild to moderate NPDR (n = 11) (P <
      0.0001). Ninety-eight percent of 46 patients (10 with AMD and 36 with DR) who
      completed the usability survey reported that the hSDH test was easy to use.
      CONCLUSIONS: This study demonstrated that the hSDH test on a mobile device is
      comparable to PC-based testing methods. As a mobile app, it is intuitive to use,
      readily accessible, and sensitive to the severity of maculopathy. It has the
      potential to provide patients having maculopathy with a new tool to monitor their
      vision at home.

PMID- 23860762
TI  - Effect of cataract surgery on optical coherence tomography measurements and
      repeatability in patients with non-insulin-dependent diabetes mellitus.
AB  - PURPOSE: To evaluate the effect of uncomplicated cataract phacoemulsification on
      macular and retinal nerve fiber layer (RNFL) thickness using two spectral-domain
      optical coherence tomography (OCT) instruments, Cirrus OCT and Spectralis OCT, in
      patients having non-insulin-dependent diabetes mellitus (NIDDM) without
      retinopathy, and to assess the reliability of the OCT measurements before and
      after cataract surgery. METHODS: The study included 35 eyes of 35 patients having
      NIDDM without retinopathy (20 men and 15 women, mean age 69.8 years, range, 48-80
      years) who underwent cataract phacoemulsification. One month before and 1 month
      after surgery, visual acuity and three repetitions of scans using the RNFL and
      macular analysis protocols of the Cirrus and Spectralis OCT instruments were
      performed. The differences between the two visits were analyzed by Student's t
      test for paired samples. Repeatability of OCT measurements was evaluated by
      calculating the coefficients of variation for each of the parameters recorded and
      for each visit. RESULTS: RNFL thicknesses provided by Cirrus and Spectralis OCT
      and macular measurements provided by Cirrus OCT differed significantly between
      the two visits. Macular thicknesses provided by Spectralis OCT before and after
      surgery were not significantly different. OCT repeatability was better after
      surgery with lower coefficients of variation for scans performed after surgical
      removal of the cataract. CONCLUSIONS: The presence of cataracts affects RNFL and
      macular measurements performed with OCT in NIDDM patients without retinopathy.
      The repeatability of the images significantly improved after cataract
      phacoemulsification.

PMID- 23860763
TI  - [Electropathology in Vienna, an exhibition on accident prevention].
AB  - Since 1906, there is, apart from the period 2000-2009, in Vienna, a collection
      about the processes and consequences of accidents involving electricity. The
      purpose of this collection is to raise awareness of the dangers, and the
      presentation of appropriate safety devices. Both in the case of industrial
      accidents and leisure accidents, the risk source of electrical power is not
      negligible. Due to the different vulnerable groups, the availability of
      prevention work is difficult. The concept of the electro-pathological collection
      in Vienna has taken this into account. 

PMID- 23860764
TI  - Insulin resistance induced by zymosan as a new animal model in mice.
AB  - Insulin resistance (IR) is known as a main problem in diabetic disorders. Some
      animal models for research in IR have been mentioned. Each model shows merit with
      some disadvantages. Thus, a new animal model for IR is required. The present
      study used zymosan, a mixture of cell-wall particles from the yeast named
      Saccharomyces cerevisiae, to establish a new model of IR in mice. Also, we
      compared the difference of this model with fructose-rich chow-induced model and
      found some merits of this model. Moreover, we identified that this model induced
      by zymosan is reversible and IR can be reversed gradually after termination of
      treatment. Taken together, we suggest zymosan as a useful agent to induce IR
      through inflammatory pathway in mice. 

PMID- 23860765
TI  - Loss of very-long O-antigen chains optimizes capsule-mediated immune evasion by
      Salmonella enterica serovar Typhi.
AB  - Expression of capsular polysaccharides is a variable trait often associated with
      more-virulent forms of a bacterial species. For example, typhoid fever is caused
      by the capsulated Salmonella enterica serovar Typhi, while nontyphoidal
      Salmonella serovars associated with gastroenteritis are noncapsulated. Here we
      show that optimization of the immune evasive properties conferred by the
      virulence-associated (Vi) capsular polysaccharide involved an additional
      alteration to the cell envelope of S. Typhi, namely inactivation of the fepE
      gene, encoding the regulator of very-long O-antigen chains. Introduction of the
      capsule-encoding viaB locus into the nontyphoidal S. enterica serovar Typhimurium
      reduced complement deposition in vitro and intestinal inflammation in a mouse
      colitis model. However, both phenotypes were markedly enhanced when the viaB
      locus was introduced into an S. Typhimurium fepE mutant, which lacks very-long O
      antigen chains. Collectively, these data suggest that during the evolution of the
      S. Typhi lineage, loss of very-long O-antigen chains by pseudogene formation was
      an adaptation to maximize the anti-inflammatory properties of the Vi capsular
      polysaccharide. IMPORTANCE: Genomic comparison illustrates that acquisition of
      virulence factors by horizontal gene transfer is an important contributor to the
      evolution of enteric pathogens. Acquisition of complex virulence traits commonly
      involves horizontal transfer of a large gene cluster, and integration of the gene
      cluster into the host genome results in the formation of a pathogenicity island.
      Acquisition of the virulence-associated (Vi) capsular polysaccharide encoded by
      SPI7 (Salmonella pathogenicity island 7) was accompanied in the human-adapted
      Salmonella enterica serovar Typhi by inactivation of the fepE gene, encoding the
      regulator of very-long O-antigen chains. We show that the resulting loss of very
      long O-antigen chains was an important mechanism for maximizing immune evasion
      mediated by the Vi capsular polysaccharide. These data suggest that successful
      incorporation of a capsular polysaccharide requires changes in the cell envelope
      of the hosting pathogen.

PMID- 23860766
TI  - Influenza viruses: breaking all the rules.
AB  - Influenza A viruses (IAV) are significant pathogens able to repeatedly switch
      hosts to infect multiple avian and mammalian species, including humans. The
      unpredictability of IAV evolution and interspecies movement creates continual
      public health challenges, such as the emergence of the 2009 pandemic H1N1 virus
      from swine, as well as pandemic threats from the ongoing H5N1 and the recent H7N9
      epizootics. In the last decade there has been increased concern about the "dual
      use" nature of microbiology, and a set of guidelines covering "dual use research
      of concern" includes seven categories of potentially problematic scientific
      experiments. In this Perspective, we consider how in nature IAV continually
      undergo "dual use experiments" as a matter of evolution and selection, and we
      conclude that studying these properties of IAV is critical for mitigating and
      preventing future epidemics and pandemics.

PMID- 23860767
TI  - Within-host evolution of Burkholderia pseudomallei over a twelve-year chronic
      carriage infection.
AB  - Burkholderia pseudomallei causes the potentially fatal disease melioidosis. It is
      generally accepted that B. pseudomallei is a noncommensal bacterium and that any
      culture-positive clinical specimen denotes disease requiring treatment. Over a 23
      year study of melioidosis cases in Darwin, Australia, just one patient from 707
      survivors has developed persistent asymptomatic B. pseudomallei carriage. To
      better understand the mechanisms behind this unique scenario, we performed whole
      genome analysis of two strains isolated 139 months apart. During this period, B.
      pseudomallei underwent several adaptive changes. Of 23 point mutations, 78% were
      nonsynonymous and 43% were predicted to be deleterious to gene function,
      demonstrating a strong propensity for positive selection. Notably, a nonsense
      mutation inactivated the universal stress response sigma factor RpoS, with
      pleiotropic implications. The genome underwent substantial reduction, with four
      deletions in chromosome 2 resulting in the loss of 221 genes. The deleted loci
      included genes involved in secondary metabolism, environmental survival, and
      pathogenesis. Of 14 indels, 11 occurred in coding regions and 9 resulted in
      frameshift mutations that dramatically affected predicted gene products.
      Disproportionately, four indels affected lipopolysaccharide biosynthesis and
      modification. Finally, we identified a frameshift mutation in both P314 isolates
      within wcbR, an important component of the capsular polysaccharide I locus,
      suggesting virulence attenuation early in infection. Our study illustrates a
      unique clinical case that contrasts a high-consequence infectious agent with a
      long-term commensal infection and provides further insights into bacterial
      evolution within the human host. IMPORTANCE: Some bacterial pathogens establish
      long-term infections that are difficult or impossible to eradicate with current
      treatments. Rapid advances in genome sequencing technologies provide a powerful
      tool for understanding bacterial persistence within the human host. Burkholderia
      pseudomallei is considered a highly pathogenic bacterium because infection is
      commonly fatal. Here, we document within-host evolution of B. pseudomallei in a
      unique case of human infection with ongoing chronic carriage. Genomic comparison
      of isolates obtained 139 months (11.5 years) apart showed a strong signal of
      adaptation within the human host, including inactivation of virulence and
      immunogenic factors, and deletion of pathways involved in environmental survival.
      Two global regulatory genes were mutated in the 139-month isolate, indicating
      extensive regulatory changes favoring bacterial persistence. Our study provides
      insights into B. pseudomallei pathogenesis and, more broadly, identifies parallel
      evolutionary mechanisms that underlie chronic persistence of all bacterial
      pathogens.

PMID- 23860768
TI  - Resistance to neuraminidase inhibitors conferred by an R292K mutation in a human
      influenza virus H7N9 isolate can be masked by a mixed R/K viral population.
AB  - We characterized the A/Shanghai/1/2013 virus isolated from the first confirmed
      human case of A/H7N9 disease in China. The A/Shanghai/1/2013 isolate contained a
      mixed population of R (65%; 15/23 clones) and K (35%; 8/23 clones) at
      neuraminidase (NA) residue 292, as determined by clonal sequencing.
      A/Shanghai/1/2013 with mixed R/K at residue 292 exhibited a phenotype that is
      sensitive to zanamivir and oseltamivir carboxylate by the enzyme-based NA
      inhibition assay. The plaque-purified A/Shanghai/1/2013 with dominant K292 (94%;
      15/16 clones) showed sensitivity to zanamivir that had decreased by >30-fold and
      to oseltamivir carboxylate that had decreased by >100-fold compared to its plaque
      purified wild-type counterpart possessing dominant R292 (93%, 14/15 clones). In
      Madin-Darby canine kidney (MDCK) cells, the plaque-purified A/Shanghai/1/2013
      NAK292 virus exhibited no reduction in viral titer under conditions of increasing
      concentrations of oseltamivir carboxylate (range, 0 to 1,000 uM) whereas the
      replication of the plaque-purified A/Shanghai/1/2013-NAR292 and the
      A/Shanghai/2/2013 viruses was completely inhibited at 250 uM and 31.25 uM of
      oseltamivir carboxylate, respectively. Although the plaque-purified
      A/Shanghai/1/2013-NAK292 virus exhibited lower NA enzyme activity and a higher Km
      for 2'-(4-methylumbelliferryl)-alpha-d-N-acetylneuraminic acid than the wild-type
      A/Shanghai/1/2013-NAR292 virus, the A/Shanghai/1/2013-NAK292 virus formed large
      plaques and replicated efficiently in vitro. Our results confirmed that the NA
      R292K mutation confers resistance to oseltamivir, peramivir, and zanamivir in the
      novel human H7N9 viruses. Importantly, detection of the resistance phenotype may
      be masked in the clinical samples containing a mixed population of R/K at NA
      residue 292 in the enzyme-based NA inhibition assay. IMPORTANCE: The
      neuraminidase (NA) inhibitors oseltamivir and zanamivir are currently the front
      line therapeutic options against the novel H7N9 influenza viruses, which possess
      an S31N mutation that confers resistance to the M2 ion channel blockers. It is
      therefore important to evaluate the sensitivity of the clinical isolates to NA
      inhibitors and to monitor for the emergence of resistant variants. We
      characterized the A/Shanghai/1/2013 (H7N9) isolate which contained a mixed
      population of R/K at NA residue 292. While the clinical isolate exhibited a
      phenotype of sensitivity to NA inhibitors using the enzyme-based NA inhibition
      assay, the plaque-purified A/Shanghai/1/2013 virus with dominant K292 was
      resistant to zanamivir, peramivir, and oseltamivir. Resistance to NA inhibitors
      conferred by the R292K mutation in a human influenza virus H7N9 isolate can be
      masked by a mixed R/K viral population, and this should be taken into
      consideration while monitoring antiviral resistance in patients with H7N9
      infection.

PMID- 23860769
TI  - Involvement of FtsE ATPase and FtsX extracellular loops 1 and 2 in FtsEX-PcsB
      complex function in cell division of Streptococcus pneumoniae D39.
AB  - The FtsEX protein complex has recently been proposed to play a major role in
      coordinating peptidoglycan (PG) remodeling by hydrolases with the division of
      bacterial cells. According to this model, cytoplasmic FtsE ATPase interacts with
      the FtsZ divisome and FtsX integral membrane protein and powers allosteric
      activation of an extracellular hydrolase interacting with FtsX. In the major
      human respiratory pathogen Streptococcus pneumoniae (pneumococcus), a large
      extracellular-loop domain of FtsX (ECL1FtsX) is thought to interact with the
      coiled-coil domain of the PcsB protein, which likely functions as a PG amidase or
      endopeptidase required for normal cell division. This paper provides evidence for
      two key tenets of this model. First, we show that FtsE protein is essential, that
      depletion of FtsE phenocopies cell defects caused by depletion of FtsX or PcsB,
      and that changes of conserved amino acids in the FtsE ATPase active site are not
      tolerated. Second, we show that temperature-sensitive (Ts) pcsB mutations
      resulting in amino acid changes in the PcsB coiled-coil domain (CCPcsB) are
      suppressed by ftsX mutations resulting in amino acid changes in the distal part
      of ECL1FtsX or in a second, small extracellular-loop domain (ECL2FtsX). Some FtsX
      suppressors are allele specific for changes in CCPcsB, and no FtsX suppressors
      were found for amino acid changes in the catalytic PcsB CHAP domain (CHAPPcsB).
      These results strongly support roles for both ECL1FtsX and ECL2FtsX in signal
      transduction to the coiled-coil domain of PcsB. Finally, we found that pcsBCC(Ts)
      mutants (Ts mutants carrying mutations in the region of pcsB corresponding to the
      coiled-coil domain) unexpectedly exhibit delayed stationary-phase autolysis at a
      permissive growth temperature. IMPORTANCE: Little is known about how FtsX
      interacts with cognate PG hydrolases in any bacterium, besides that ECL1FtsX
      domains somehow interact with coiled-coil domains. This work used powerful
      genetic approaches to implicate a specific region of pneumococcal ECL1FtsX and
      the small ECL2FtsX in the interaction with CCPcsB. These findings identify amino
      acids important for in vivo signal transduction between FtsX and PcsB for the
      first time. This paper also supports the central hypothesis that signal
      transduction between pneumococcal FtsX and PcsB is linked to ATP hydrolysis by
      essential FtsE, which couples PG hydrolysis to cell division. The classical
      genetic approaches used here can be applied to dissect interactions of other
      integral membrane proteins involved in PG biosynthesis. Finally, delayed
      autolysis of the pcsBCC(Ts) mutants suggests that the FtsEX-PcsB PG hydrolase may
      generate a signal in the PG necessary for activation of the major LytA autolysin
      as pneumococcal cells enter stationary phase.

PMID- 23860771
TI  - TRUS-MRI image registration: a paradigm shift in the diagnosis of significant
      prostate cancer.
AB  - Accuracy of multiparametric MRI has greatly improved the ability of localizing
      tumor foci of prostate cancer. This property can be used to perform a TRUS-MR
      image registration, new technological advance, which allows for an overlay of an
      MRI onto a TRUS image to target a prostate biopsy toward a suspicious area Three
      types of registration have been developed: cognitive-based, sensor-based, and
      organ-based registration. Cognitive registration consists of aiming a suspicious
      area during biopsy with the knowledge of the lesion location identified on
      multiparametric MRI. Sensor-based registration consists of tracking in real time
      the TRUS probe with a magnetic device, achieving a global positioning system
      which overlays in real-time prostate image on both modalities. Its main
      limitation is that it does not take into account prostate and patient motion
      during biopsy. Two systems (Artemis and Uronav) have been developed to partially
      circumvent this drawback. Organ-based registration (Koelis) does not aim to track
      the TRUS probe, but the prostate itself to compute in a 3D acquisition the TRUS
      prostate shape, allowing for a registration with the corresponding 3D MRI shape.
      This system is not limited by prostate/patient motion and allows for a
      deformation of the organ during registration. Pros and cons of each technique and
      the rationale for a targeted biopsy only policy are discussed. 

PMID- 23860770
TI  - A mouse model for human norovirus.
AB  - Human noroviruses (HuNoVs) cause significant morbidity and mortality worldwide.
      However, despite substantial efforts, a small-animal model for HuNoV has not been
      described to date. Since "humanized" mice have been successfully used to study
      human-tropic pathogens in the past, we challenged BALB/c mice deficient in
      recombination activation gene (Rag) 1 or 2 and common gamma chain (gammac) (Rag
      gammac) engrafted with human CD34+ hematopoietic stem cells, nonengrafted
      siblings, and immunocompetent wild-type controls with pooled stool isolates from
      patients positive for HuNoV. Surprisingly, both humanized and nonhumanized BALB/c
      Rag-gammac-deficient mice supported replication of a GII.4 strain of HuNoV, as
      indicated by increased viral loads over input. In contrast, immunocompetent wild
      type BALB/c mice were not infected. An intraperitoneal route of infection and the
      BALB/c genetic background were important for facilitating a subclinical HuNoV
      infection of Rag-gammac-deficient mice. Expression of structural and
      nonstructural proteins was detected in cells with macrophage-like morphology in
      the spleens and livers of BALB/c Rag-gammac-deficient mice, confirming the
      ability of HuNoV to replicate in a mouse model. In summary, HuNoV replication in
      BALB/c Rag-gammac-deficient mice is dependent on the immune-deficient status of
      the host but not on the presence of human immune cells and provides the first
      genetically manipulable small-animal model for studying HuNoV infection.
      IMPORTANCE: Human noroviruses are a significant cause of viral gastroenteritis
      worldwide, resulting in significant morbidity and mortality. Antivirals and
      vaccines are currently not available, in part due to the inability to study these
      viruses in a genetically manipulable, small-animal model. Herein, we report the
      first mouse model for human noroviruses. This model will accelerate our
      understanding of human norovirus biology and provide a useful resource for
      evaluating antiviral therapies.

PMID- 23860772
TI  - Microfluidic technique to measure intratumoral transport and calculate drug
      efficacy shows that binding is essential for doxorubicin and release hampers
      Doxil.
AB  - Intratumoral transport and binding are important mechanisms that determine the
      efficacy of cancer drugs. Current drug screening methods rely heavily on
      monolayers of cancer cells, which overlook the contribution of tissue-level
      transport and binding. To quantify these factors, we developed a method that
      couples an in vitro, drug-delivery device containing a three-dimensional cell
      mass and a mathematical model of drug diffusion, binding to DNA, release from
      carriers, and clearance. Spheroids derived from LS174T human colon carcinoma
      cells were inserted into rectangular chambers to form rectangular cell masses
      (tissue) and subjected to continuous medium perfusion. To simulate drug delivery
      and clearance, the tissues were treated with doxorubicin followed by drug-free
      medium. To evaluate the effect of liposome encapsulation, tissues were treated
      with liposome-encapsulated doxorubicin (Doxil). Spatiotemporal dynamics of drug
      distribution and apoptosis was measured by fluorescence microscopy. The
      diffusivity and DNA binding constant of doxorubicin were determined by fitting
      experimental data to the mathematical model. Results show that an ideal
      combination of diffusivity, binding constant, clearance rate, and cytotoxicity
      contribute to the high therapeutic efficacy of doxorubicin. There was no
      detectable release of doxorubicin from Doxil in the tissues. The rate of
      doxorubicin release, evaluated by fitting experimental data to the mathematical
      model, was below therapeutically effective levels. These results show that
      despite enhanced systemic circulation obtained by liposome encapsulation, the
      therapeutic effect of Doxil is limited by slow intratumoral drug release. The
      experimental and computational methods developed here to calculate drug efficacy
      provide mechanisms to explain poor performance of drug candidates, and enable
      design of more successful cancer drugs.

PMID- 23860773
TI  - P53 codon 72 Arg/Pro polymorphism and glioma risk: an updated meta-analysis.
AB  - P53 codon 72 Arg/Pro is a C/G variation upstream of the p53 gene on human
      chromosome 17p13. Many case-control studies have investigated the association
      between p53 codon 72 Arg/Pro polymorphism and glioma risk but provided
      inconsistent findings. To better understand the pathogenesis of glioma, we
      performed the current meta-analysis by pooling data from all available individual
      studies. According to the inclusion criteria, ten independent publications with
      11 case-control studies were included into this meta-analysis. The pooled odds
      ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the
      effect of p53 codon 72 Arg/Pro variant on the development of glioma. Overall, no
      appreciable correlation was observed among the total studies in all gene models
      (ORPro allele vs. Arg allele = 1.04, 95 % CI = 0.90-1.20, P OR = 0.581; ORPro/Pro
      vs. Arg/Arg = 0.95, 95 % CI = 0.80-1.14, P OR = 0.614; ORPro/Arg vs. Arg/Arg =
      1.01, 95 % CI = 0.79-1.29, P OR = 0.993; ORPro/Arg + Pro/Pro vs. Arg/Arg = 1.03,
      95 % CI = 0.82-1.29, P OR = 0.799; ORPro/Pro vs. Arg/Arg + Pro/Arg = 1.02, 95 %
      CI = 0.86-1.22, P OR = 0.785). In stratified analyses by ethnicity, source of
      controls, and glioma subtypes, the p53 codon 72 Arg/Pro polymorphism did not
      alter the risk for glioma in population-based, hospital-based, astrocytoma, and
      oligodendroglioma studies among Caucasian. Interestingly, the Pro/Pro genotype
      seemed to be negatively associated with the glioma risk among patients with
      glioblastoma (ORPro/Pro vs. Arg/Arg = 0.68, 95 % CI = 0.48-0.95, P OR = 0.026).
      Our study suggests that the polymorphism of p53 codon 72 Arg/Pro may play a
      protective role in the development of glioblastoma. The relationship of p53 codon
      72 Arg/Pro polymorphism with the susceptibility to glioma needs further
      estimation by more individual studies with high quality across ethnicities.

PMID- 23860774
TI  - Quantitative assessment of the association between CYP1A1 A4889G polymorphism and
      endometrial cancer risk.
AB  - Cytochrome P450 1A1 (CYP1A1) A4889G polymorphism was supposed to be associated
      with endometrial cancer risk, but previous studies reported conflicting results.
      We therefore performed a meta-analysis of all relevant studies to get a
      comprehensive assessment of the association between CYP1A1 A4889G polymorphism
      and endometrial cancer risk. The pooled odds ratios (OR) with the corresponding
      95% confidence interval (95% CI) was calculated to assess the association.
      Finally, ten studies with a total of 1,682 endometrial cancer cases and 2,510
      controls were finally included into the meta-analysis. Meta-analysis of the total
      ten studies showed that CYP1A1 A4889G polymorphism was not associated with
      endometrial cancer risk (ORG versus A = 1.14, 95% CI 0.83-1.57, P OR = 0.417;
      ORGG versus AA = 1.23, 95% CI 0.70-2.18, P OR = 0.470; ORGG versus AA/AG = 1.03,
      95% CI 0.59-1.81, P OR = 0.919; ORGG/AG versus AA = 1.22, 95% CI 0.82-1.81, P OR
      = 0.336). Subgroup analyses by ethnicity further showed that there was also no
      obvious association between CYP1A1 A4889G polymorphism and endometrial cancer
      risk in both Caucasians and Asians. Sensitivity analysis by excluding single
      study in turns showed that the pooled estimations were not stable. Therefore,
      evidence for currently available data suggests that CYP1A1 A4889G polymorphism is
      not associated with endometrial cancer risk. However, more studies with large
      number of participants are needed to further assess the association precisely.

PMID- 23860775
TI  - MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1
      deficiency.
AB  - Breast cancer is a complex disease; the molecular mechanisms involved in sporadic
      breast carcinogenesis remain to be elucidated. The present study aimed to explore
      the deficiency of breast cancer susceptibility gene 1 (BRCA1), including protein
      loss expression, promoter hypermethylation and gene copy deletion, its
      correlationship with other tumor markers expression (TP53, MYC, etc.), and
      clinical significance in sporadic breast cancer. BRCA1 protein expression was
      negative in 226 of 374 (60.4%) cases of this study. Cases negative for BRCA1
      protein were more often with pathological tumor-node-metastasis stage III,
      positive for lymph node metastasis and MYC overexpression than BRCA1-positive
      tumors. BRCA1 hypermethylation was detected in 16.4% (31 of 189) breast cancers,
      which correlated with BRCA1 negative, ER negative, MYC overexpression, and triple
      negative phenotype. In addition, the percentage of cells with BRCA1 gene copy
      deletion was significantly increased in BRCA1-methylated tumors. Kaplan-Meier
      survival analysis showed that patients with BRCA1-negative expression showed a
      worse overall survival (OS) than those with BRCA1-positive expression, and
      patients with BRCA1-methylated tumors had a significantly worse disease-free
      survival than did patients with unmethylated tumors. Furthermore, BRCA1
      hypermethylation showed an inverse association with OS in LN-positive or p53
      negative subgroup patients. Importantly, uni- and multivariate Cox regression
      analyses revealed that BRCA1 was an independent prognostic indicator of OS in
      sporadic breast cancer. Thus, we found MYC overexpression and poor prognosis in
      sporadic breast cancer with BRCA1 deficiency. The targeting of BRCA1 deficiency
      in combination with MYC-pathways inhibitors may provide a promising strategy for
      sporadic breast cancer care, the triple-negative subtype in particular.

PMID- 23860776
TI  - Raman spectroscopy-based approach to detect aging-related oxidative damage in the
      mouse oocyte.
AB  - PURPOSE: Detection of chemical modifications induced by aging-related oxidative
      damage in mouse metaphase II (MII) oocytes by Raman microspectroscopy. METHODS:
      CD-1 mice at the age of 4-8 weeks (young mice) and 48-52 weeks (old mice), were
      superovulated and oocytes at metaphase II stage were recovered from oviducts. MII
      oocytes from young animals were divided into three groups: A) young oocytes,
      processed immediately after collection; B) in vitro aged oocytes, cultured in
      vitro for 10 h before processing; C) oxidative-stressed oocytes, exposed to 10 mM
      hydrogen peroxide for 2 min before processing. Oocytes from reproductively old
      mice were referred to as old oocytes (D). All the oocytes were analyzed by
      confocal Raman microspectroscopy. The spectra were statistically analyzed using
      Principal Component Analysis (PCA). RESULTS: PCA evidenced that spectra from
      young oocytes (A) were clearly distinguishable from those obtained from in vitro
      aged, oxidative-damaged and old oocytes (B, C, D) and presented significant
      differences in the bands attributable to lipid components (C = C stretching,
      1,659 cm-1; CH2 bending, 1,450 cm-1; CH3 deformation,1,345 cm-1; OH bending, C-N
      stretching, 1,211 cm-1) and protein components (amide I band,1,659 cm-1; CH2
      bending modes and CH3 deformation, 1,450 cm-1; C-N and C-C stretching vibrations,
      1,132 cm-1; phenylalanine's vibration, 1,035 cm-1) CONCLUSIONS: Raman
      spectroscopy is a valuable non-invasive tool for the identification of
      biochemical markers of oxidative damage and could represent a highly informative
      method of investigation to evaluate the oocyte quality.

PMID- 23860777
TI  - The divergence and natural selection of autocatalytic primordial metabolic
      systems.
AB  - The diversity of the central metabolism of modern organisms is caused by the
      existence of a few metabolic modules, combination of which produces multiple
      metabolic pathways. This paper analyzes biomimetically reconstructed coupled
      autocatalytic cycles as the basis of ancestral metabolic systems. The mechanism
      for natural selection and evolution in autocatalytic chemical systems may be
      affected by natural homeostatic parameters such as ambient chemical potentials,
      temperature, and pressure. Competition between separate parts of an autocatalytic
      network with positive-plus-negative feedback resulted in the formation of
      primordial autotrophic, mixotrophic, and heterotrophic metabolic systems. This
      work examined the last common ancestor of a set of coupled metabolic cycles in a
      population of protocells. Physical-chemical properties of these cycles determined
      the main principles of natural selection for the ancestral Bacteria and Archaea
      taxa. 

PMID- 23860779
TI  - Answer to the Letter to the Editor of I. Berg et al. concerning "Adolescent
      idiopathic scoliosis treated with posteromedial translation: radiologic
      evaluation with a 3D low-dose system" by B. Ilharreborde, G. Sebag, W. Skalli and
      K. Mazda; Eur Spine J (2013) Apr 12 [doi:10.1007/s00586-013-2902-6].

PMID- 23860778
TI  - Correction of pelvic obliquity in neuromuscular spinal deformities using the "T
      construct": results and complications in a prospective series of 60 patients.
AB  - BACKGROUND: We present the results of a prospective series of 60 patients treated
      for neuromuscular spinal deformities with an original spinopelvic construct using
      two sacral screws and two iliac screws. Clinical and radiological results
      obtained with this new surgical technique were studied and discussed according to
      the epidemiological data and relevant literature. METHODS: From January 2008 to
      June 2010, the clinical data of every patient who underwent spinopelvic fixation
      for treatment of a neuromuscular spinal deformity were recorded prospectively.
      RESULTS: Sixty patients were operated on during the study period. Spinal
      correction and fusion was performed by posterior approach. In six patients with a
      residual spinopelvic imbalance more than 15 degrees  on lateral preoperative
      bending films, an anterior release of the thoracolumbar junction was performed on
      the same day, before posterior correction. Preoperative pelvic obliquity (PO)
      ranged from 4 degrees  to 44 degrees  (mean 21.6 degrees ). Postoperative pelvic
      obliquity ranged from 0 degrees  to 14 (mean 4.6 degrees ). No significant loss
      of correction was noted at the last follow-up. One patient died 3 months after
      the initial procedure due to respiratory compromise. 11 patients had early
      postoperative infections of the posterior approach. CONCLUSIONS: Despite a high
      rate of infectious complications, optimal correction of pelvic obliquity requires
      extension of spinal instrumentation to the pelvis. Spinopelvic fixation remains a
      difficult challenge in neurological patients with hypotrophy. We think that
      pelvic fixation with the "T construct" did provide effective and improved spinal
      stabilization in these patients, while reducing the need for a postoperative cast
      or brace. As a result, patients had a favourable postoperative course with early
      mobilization and return to a comfortable sitting position.

PMID- 23860780
TI  - Combined C-H functionalization/O-H insertion reaction to form tertiary beta
      alkoxy substituted beta-aminophosphonates catalyzed by [Cu(MeCN)4]PF6.
AB  - The copper-catalyzed C-H functionalization/O-H insertion reaction of alpha
      diazophosphonates with alcohols has been developed with iodine as an additive. In
      order to understand this reaction, we present here a possible mechanism for the
      combined reaction. This process provides straightforward access to tertiary beta
      alkoxy substituted beta-aminophosphonate derivatives with moderate to good
      yields. 

PMID- 23860781
TI  - Maintenance therapy with pegaptanib sodium for neovascular age-related macular
      degeneration: an exploratory study in Japanese patients (LEVEL-J study).
AB  - PURPOSE: To explore the efficacy and safety of pegaptanib sodium as maintenance
      therapy in Japanese patients with neovascular, age-related macular degeneration
      (AMD) after induction therapy (LEVEL-J study). METHODS: A multi-center,
      prospective study was conducted at 21 medical institutions between 2009 and 2011.
      Of Japanese neovascular AMD patients with choroidal neovascularization who showed
      improvement in visual acuity (VA) with induction therapy, those who were
      scheduled for intravitreal injections of pegaptanib as maintenance therapy were
      recruited. LogMAR VA was assessed. Booster treatment (unscheduled treatment with
      other agents) was allowed during the study period if symptoms were judged to have
      worsened. Safety was assessed by monitoring adverse events and intraocular
      pressure (IOP). RESULTS: Of 75 patients included in the analysis, 80 % completed
      the 54-week study period. Their mean age was 74.7 +/- 6.9 years, and 54 patients
      (72.0 %) were men. The mean number of pegaptanib injections was 5.7 +/- 2.6.
      Booster treatment was not required in 40 eyes (53.3 %). Mean logMAR VA was 0.61
      +/- 0.31 before induction therapy, 0.26 +/- 0.24 before maintenance therapy, and
      0.29 +/- 0.28 at 54 weeks. No notable change in VA was observed during
      maintenance therapy. Adverse events were reported in 4 patients (5.3 %),
      including increased intraocular pressure, cancer, gallstones and recurrence of
      breast cancer, but mean IOP remained stable during maintenance therapy.
      CONCLUSIONS: The results of this exploratory study suggest that maintenance
      therapy with pegaptanib is potentially an effective and well-tolerated option in
      Japanese patients with neovascular AMD in whom induction therapy has been
      successful.

PMID- 23860782
TI  - Prognostic factors predicting the surgical outcome of bilateral lateral rectus
      recession surgery for patients with infantile exotropia.
AB  - PURPOSE: To determine the presurgery factors affecting early and long-term
      favorable outcomes of bilateral lateral rectus recession surgery for infantile
      exotropia. PATIENTS AND METHODS: A retrospective study of 50 patients with
      infantile exotropia (both constant-type and intermittent-type exotropia with
      onset before 1 year of age) who had bilateral lateral rectus recession surgery
      correction with more than 1 year follow up. Presurgery data were obtained and
      evaluated by use of multiple regression analysis. RESULTS: Smaller presurgery
      distance deviation (p = 0.042), older age at surgery (p = 0.025), longer interval
      between onset and surgery (p = 0.020), and more myopic refractive error (p =
      0.007) were associated with successful outcome at 6 weeks, but none was
      correlated with successful outcome at 1 year. Among all data, presurgery distance
      deviation was the only significant determinant (multiple regression analysis, p =
      0.021) for successful outcome at 6 weeks. Presurgery distance deviation (beta =
      0.952, p < 0.001) was correlated with the distant angle of deviation 6 weeks
      (beta = 0.952, p < 0.001) and 1 year (beta = 0.394, p = 0.006) postsurgery.
      CONCLUSIONS: Smaller presurgery deviation was found to be associated with more
      favorable surgical outcome.

PMID- 23860783
TI  - Immunizations and the power of school nursing.

PMID- 23860784
TI  - Presidential inaugural address: school nursing into the future, supporting
      education, advancing student health.

PMID- 23860785
TI  - [The Konigsteiner Empfehlung of 2012 - essential alterations and modifications].
AB  - BACKGROUND: Since 1974, the recommendation for assessment of hearing impairment
      caused by noise - formerly known as "Konigsteiner Merkblatt" (now: "Konigsteiner
      Empfehlung") - has been representing the state of the art for the assessment of
      the occupational disease BK-No. 2301. It was updated several times, the last time
      in 2012. It provides a summary of the current medical knowledge. A new
      measurement for the entire working life - the Effective Noise Dose by Liedtke -
      was introduced. Otoacoustic emissions (OAE) are now the crucial tests in order to
      detect a hair cell dysfunction. As from now the tinnitus has to be put under a
      more comprehensive examination. On the strength of post experience the previous
      speech audiometry (Freiburger Test) is reliable, it was retrained. In future the
      indication for hearing aids will be oriented towards the aid guidelines of the
      legal health insurance. The questionnaire for the expert opinion was revised and
      the fee was adapted.

PMID- 23860786
TI  - Development and characterization of AND-gate dynamic controllers with a modular
      synthetic GAL1 core promoter in Saccharomyces cerevisiae.
AB  - Expression of heterologous proteins in metabolic engineering endeavors can be
      detrimental to host cells due to increased usage of cellular resources. Dynamic
      controls, where protein expression can be triggered on-demand, are effective for
      the engineering and optimization of bio-catalysts towards robust cell growth and
      enhanced biochemical productivity. Here, we describe the development and
      characterization of AND-gate dynamic controllers in Saccharomyces cerevisiae
      which combine two dynamic control strategies, inducible promoters and sensing
      regulation. These dynamic controllers were constructed based on synthetic hybrid
      promoters. Promoter enhancer sequences were fused to a synthetic GAL1 core
      promoter containing DNA binding sites for the binding of a repressor that reduced
      DNA affinity upon interaction with key intermediates in a biochemical pathway. As
      fatty acids are key intermediates for production of fatty alcohols, fatty acid
      esters, alkenes, and alkanes, which are advanced biofuels, we used the fatty acid
      responsive FadR repressor and its operator sequence to demonstrate the
      functionality of the dynamic controllers. We established that the synthetic GAL1
      core promoter can be used as a modular promoter part for constructing synthetic
      hybrid promoters and conferring fatty acid inducibility. We further showed the
      performance of the AND-gate dynamic controllers, where two inputs (fatty acid and
      copper presence/phosphate starvation) were required to switch the AND-gate ON.
      This work provides a convenient platform for constructing AND-gate dynamic
      controllers, that is, promoters that combine inducible functionality with
      regulation of protein expression levels upon detection of key intermediates
      towards the engineering and optimization of bio-catalytic yeast cells.

PMID- 23860787
TI  - S-osteotomy with lengthening and then nailing compared with traditional Ilizarov
      method.
AB  - PURPOSE: The purpose of this study was to explore the clinical effect of the
      novel method combined longitudinal S-osteotomy and Lengthen And Then Nail (LATN)
      technique for leg lengthening and compare with the classic Ilizarov method.
      METHODS: This retrospective study was performed from March 2008 to April 2012. A
      total of 176 leg lengthenings (88 consecutive patients) were performed at our
      institution. The mean duration of follow-up was 2.2 years (range, one to four
      years). In group A, 78 tibial lengthenings were performed with longitudinal S
      osteotomy and LATN technique. In group B, 98 tibial lengthenings were performed
      with the classic method. The final gain in length, mean surgical time for
      bilateral tibial osteotomy, the external fixation index and the radiographic
      consolidation index were calculated and compared. The complications encountered
      during operation and follow-up were documented. RESULTS: There was no significant
      difference in the final gain in length between the two groups. Mean surgical time
      in group A (130.05 +/- 6.60 min) was significantly longer than that in group B
      (91.4 +/- 6.61 min; P < 0.05). External fixation index in group A (21.02 +/- 3.16
      days/cm) was significantly lower than that in group B (76.19 +/- 8.32 days/cm; P
      < 0.05). Consolidation index was significantly lower (more rapid healing) in
      group A (43.38 +/- 5.35 days/cm) than that in group B (76.19 +/- 8.32 days/cm; P
      < 0.05). There was a significant difference in pin-tract problems and axial
      deviation between the two groups. CONCLUSION: The novel method combined
      longitudinal S-corticotomy and LATN technique safely reduces the consolidation
      time, rate of pin-tract problems and axial deviation during leg lengthening,
      compared with the classic Ilizarov method.

PMID- 23860788
TI  - Avulsion fracture of the supinator crest of the proximal ulna in the context of
      elbow joint injuries.
AB  - PURPOSE: While performing CT examinations of the elbow, we frequently observed a
      previously undescribed fracture fragment of the supinator crest of the ulna.
      According to the anatomy of the lateral collateral ligament complex, this
      fracture might be an avulsion fracture of the annular ligament and/or the lateral
      ulnar collateral ligament. The aim of this study was to further characterize
      these fragments and document their associated injuries. METHODS: Retrospective
      evaluation of CT scans of the elbow was performed. Conventional X-ray and CT
      diagnoses were used to systematically document any associated injuries. RESULTS:
      A total of 152 CT scans were evaluated. The fragment in question was discovered
      in 17 patients (11.2%). The average age of the patients was 40 years (+/-14.9; 9
      71 years). The fragment size varied between a few millimetres and 2.4 cm.
      Multifragmented fractures were observed. In 82.3% of the cases, associated radial
      head fractures were diagnosed. In 29.4%, a coronoid process fracture was present.
      Distal humerus fractures were found in 23.5%. Instability in the medial
      collateral ligament and an Osborne-Cotterill lesion were found in 11.8% of the
      patients, respectively. CONCLUSIONS: In a significant percentage of the
      population, a previously undescribed fracture fragment of the supinator crest of
      the ulna could be detected. The most frequently occurring associated injuries
      were fractures of the radial head, the coronoid process, and the distal humerus.
      The aetiology of these lesions is unknown; however, bony avulsion of the annular
      or the lateral ulnar collateral ligament seems to be the most likely cause. If
      this fragment is to be diagnosed by CT, the possibility of lateral or
      posterolateral instability should be considered.

PMID- 23860789
TI  - Bony impingement depends on the bone morphology of the hip after total hip
      arthroplasty.
AB  - PURPOSE: The purpose of this study was to evaluate whether the bone morphology of
      the hip affects the range of motion (ROM) in total hip arthroplasty (THA).
      METHODS: Using the CT data of 63 patients who underwent THA, we calculated the
      ROM of flexion (Flex), internal rotation (Int-R) and external rotation (Ext-R)
      using 3D dynamic analysis software. We measured the distance between the anterior
      surface of the stem and anterior aspect of the greater trochanter (GTa length) at
      the cutting point and between the tip of the antero-inferior iliac spine (AIIS)
      and coronal plane of both femoral heads (AIIS length), as a parameter of the
      femur and pelvis, respectively. The relationship between the ROM, bone anatomy
      and impingement site was evaluated. RESULTS: We found a significant decrease in
      the ROM of Flex and the Int-R to be inversely proportional to the GTa and AIIS
      length. In Flex and Int-R, the anterior intertrochanteric region often impinges
      on the AIIS in patients with larger bone anatomy. CONCLUSIONS: We demonstrated
      that the bone morphology of the hip substantially affects the ROM of Flex and Int
      R, especially in patients with large bone anatomy. For these patients we should
      consider bony impingement in THA.

PMID- 23860790
TI  - Impact of preoperative myocardial infarction on surgical outcomes in inpatient
      orthopaedic surgery.
AB  - PURPOSE: The purpose of this study was to evaluate the impact of a preoperative
      myocardial infarction (MI) on outcomes of inpatient orthopaedic operations.
      METHODS: The National Surgical Quality Improvement Program database was used to
      identify patients who underwent common orthopaedic operations from 2006 to 2010.
      Patient demographic data, comorbidities, complications, and lengths of stay were
      collected. Multivariate logistic regression and linear regression models were
      used to compare outcomes for patients with and without a history of MI in the six
      months prior to surgery. RESULTS: Of the 32,462 patients identified, 86 had
      sustained an MI in the six months prior to surgery. The MI cohort had no cardiac
      complications but had increased incidences of superficial surgical site
      infection, unplanned re-intubation, ventilator-assisted respiration for more than
      48 hours, pneumonia, sepsis or septic shock, and postoperative mortality within
      30 days of surgery, as well as prolonged lengths of stay. Following logistic
      regression to adjust for baseline differences, a history of MI showed no
      association with cardiac complications and was significantly associated with
      superficial surgical site infection (OR 3.6, 95% CI 1.1-11.8), ventilator
      dependence for over 48 hours (OR 4.0, 95% CI 1.1-14.0), and extended length of
      stay (median with interquartile range 4 [4-4] vs. 5 [5-5] days). CONCLUSIONS: A
      myocardial infarction within six months prior to orthopaedic surgery is not
      associated with a higher risk of 30-day perioperative cardiac complications;
      however, it is associated with increased rates of surgical site infection,
      prolonged ventilator dependence, and longer hospital stay.

PMID- 23860791
TI  - Arthroscopic synovectomy in pigmented villonodular synovitis of the knee:
      clinical series and outcome.
AB  - PURPOSE: The aim of this study was to evaluate the long-term results of
      arthroscopic excision of pigmented villonodular synovitis (PVNS) of the knee
      joint. METHODS: We retrospectively assessed the results of arthroscopic excision
      of PVNS done in 40 patients from 1987 to 2012 by the senior author (JVS). No
      radiotherapy was given to any patient. All patients were followed for a mean of
      seven years. At follow-up functional assessment was done using the Lysholm score.
      Recurrence-free survival and recurrence-free survival probability were
      calculated. RESULTS: No recurrence was noted in the localised variety. In the
      diffuse variety the five year recurrence-free survival probability was 57%.
      Twelve patients developed recurrences between three months and two years. No
      recurrence was noted after two years. The mean recurrence interval was 6.25
      months. CONCLUSIONS: We concluded from this series that arthroscopic excision is
      an effective treatment for localised as well as diffuse PVNS. Recurrences can
      also be successfully dealt with by arthroscopic excision with excellent
      functional outcome.

PMID- 23860792
TI  - Influence of cryopreservation, cultivation time and patient's age on gene
      expression in Hyalograft(r) C cartilage transplants.
AB  - PURPOSE: Our aim was to evaluate the impact of cryopreservation, cultivation time
      and patient's age on the expression of specific chondrogenic markers in
      Hyalograft(r) C transplants. METHODS: Gene expression of chondrocyte markers
      [collagen type I (COL1A1), COL2A1, aggrecan, versican, melanoma inhibitory
      activity (MIA) and interleukin (IL)-1beta] was analysed in cartilage biopsies (n
      = 17) and Hyalograft(r) C transplant samples (non-cryopreserved = 78,
      cryopreserved = 13) by quantitative real-time polymerase chain reaction (PCR).
      Correlation analyses were performed to evaluate the influence of the above-named
      parameters on the level of gene expression. RESULTS: Cryopreservation of cells
      was found to decrease COL2A1 and MIA significantly (4.6-fold, p < 0.01 and 2
      fold, p < 0.045, respectively). The duration of cryopreservation had no further
      influence on the expression of these factors. No correlation was detected between
      cultivation time (75 +/- 31 days) and the expression level of any gene. Cartilage
      transplants from older patients (>35 years) exhibited a significantly higher IL
      1beta expression (3.7-fold, p < 0.039) than transplants from younger patients (<=
      35 years). CONCLUSIONS: Our data demonstrate that cryopreservation has a profound
      impact on chondrocyte metabolic activity by decreasing the expression of COL2A1
      and MIA in Hyalograft(r) C transplants, independent of the duration of
      cryopreservation.

PMID- 23860793
TI  - Metal hypersensitivity and metal ion levels in patients with coated or uncoated
      total knee arthroplasty: a randomised controlled study.
AB  - PURPOSE: Metal ion release by orthopaedic implants may cause local and systemic
      effects and induce hypersensitivity reactions. Coated implants have been
      developed to prevent or reduce these effects. This study was initiated to
      investigate the safety of a novel coating for total knee arthroplasty (TKA)
      implants. METHODS: A total of 120 patients undergoing primary TKA with no history
      of hypersensitivity and no other metal implant were randomised to receive either
      a coated or uncoated implant. Chromium (Cr), cobalt (Co), molybdenum (Mb) and
      nickel (Ni) hypersensitivity patch testing and plasma ion concentrations were
      evaluated pre-operatively and one year post-operatively. RESULTS: At the one year
      follow-up both groups demonstrated significant improvement in knee function and
      quality of life. One new weakly positive reaction to Co in the TKA group with
      coated implant and two doubtful skin reactions to Ni (one in each group) were
      noted. Even with sensitisation to implant materials no skin reactions were
      observed. Plasma metal ion concentrations did not increase and were not elevated
      at the one year follow-up in either group. CONCLUSIONS: Sensitisation after TKA
      was rare and had no influence on clinical results. TKA with coated implant and
      standard TKA demonstrated no plasma metal ion elevation.

PMID- 23860794
TI  - Genome-wide annotation of genes and noncoding RNAs of foxtail millet in response
      to simulated drought stress by deep sequencing.
AB  - Drought is a major abiotic stress that affects plant growth, production, and
      survival. Plants have evolved sophisticated and highly complex reactions to
      drought stress, including large-scale transcriptome reconfiguration. Foxtail
      millet (Setaria italica) is a member of the Poaceae family. Because of its
      outstanding tolerance to drought stress foxtail millet has the potential to
      become a new model organism. To enrich our knowledge of the processes that
      contribute to drought resistance, we have used a deep sequencing approach to
      generate a genome-wide transcriptome of foxtail millet after exposure to
      simulated drought stress. A large number of differentially expressed genes were
      characterized; in particular, we examined the roles of small interfering RNAs
      (siRNAs) and long noncoding RNAs (lncRNAs) in response to a water-deficit
      condition. These RNAs have remained largely unexplored in previous studies of
      stress-induced transcriptomes. We found that the reduced levels of 24-nt siRNA
      flanking genes were associated, for the most part, with proximal up-regulated
      genes, indicating a potential effect of 24-nt siRNAs on drought-regulated gene
      expression. Several lncRNAs that responded to the simulated drought stress were
      also identified, and we found that one of them shared sequence conservation and
      colinearity with its counterpart in sorghum (Sorghum bicolor). Our findings
      provide new insights into drought-induced changes in the foxtail millet
      transcriptome. 

PMID- 23860795
TI  - Functional evolution of cis-regulatory modules of STMADS11 superclade MADS-box
      genes.
AB  - Evolution of phenotypic morphologies is closely associated with modular
      organization of cis-regulatory elements underlying expression divergence. The
      MADS-box gene family is the subject of extensive studies that try to unscramble
      the structural complexity of flowering plants. This study is envisaged to explore
      the potential of CRMs in highly constrained non-coding elements of
      STMADS11superclade MADS-box genes in expression divergence. Phylogenetic
      reconstruction differentiated the STMADS11 genes into SVP-like, ZMM19-like, MPF1
      like and MPF2-like clades. Differential gene expression in vegetative and floral
      organs was evident within the clades as well as at inter-clade level. The genomic
      DNA search for clusters of short motifs and sequence conservation of the -2 kb
      promoter region of particularly, MPF2-like clade permitted to establish three
      well defined CRMs where transcription factors bind, being CRM1 the activator,
      CRM2 the repressor, and CRM3 the enhancer element. Similar clusters were also
      mapped in the large 1st introns in the coding region. Within these CRMs many
      transcription factor-binding sites, particularly the hotspots for MADS-domain TF
      binding elements--CArG-boxes, directing sepal specific expression in Arabidopsis-
      were accrued in the CRM1 of MPF2-like promoters. Site-directed mutagenesis and
      motif swapping through reporter assays allude towards their implication as
      functionally active elements. In terms of directional evolution of MPF2-like
      promoters, CRMs are significantly more conserved than flanking regions, hence,
      bearing the signatures for purifying selection. Thus, CRMs are the pervasive
      feature of STMADS11 genes and mutations and/or appearance of new transcription
      factor binding sites and position of the CRMs are responsible for the divergence
      in expression patterns in this clade. These results have implications in
      understanding functional evolution of cis-regulatory modules in plants.

PMID- 23860796
TI  - Sexual dimorphic floral development in dioecious plants revealed by
      transcriptome, phytohormone, and DNA methylation analysis in Populus tomentosa.
AB  - Dioecious plants have evolved sex-specific floral development mechanisms.
      However, the precise gene expression patterns in dioecious plant flower
      development remain unclear. Here, we used andromonoecious poplar, an exceptional
      model system, to eliminate the confounding effects of genetic background of
      dioecious plants. Comparative transcriptome and physiological analysis allowed us
      to characterize sex-specific development of female and male flowers.
      Transcriptome analysis identified genes significantly differentially expressed
      between the sexes, including genes related to floral development, phytohormone
      synthesis and metabolism, and DNA methylation. Correlation analysis revealed a
      significant correlation between phytohormone signaling and gene expression,
      identifying specific phytohormone-responsive genes and their cis-regulatory
      elements. Two genes related to DNA methylation, METHYLTRANSFERASE1 (MET1) and
      DECREASED DNA METHYLATION 1 (DDM1), which are located in the sex determination
      region of Chromosome XIX, have differential expression between female and male
      flowers. A time-course analysis revealed that MET1 and DDM1 expression may
      produce different DNA methylation levels in female and male flowers.
      Understanding the interactions of phytohormone signaling, DNA methylation and
      target gene expression should lead to a better understanding of sexual
      differences in floral development. Thus, this study identifies a set of candidate
      genes for further studies of poplar sexual dimorphism and relates sex-specific
      floral development to physiological and epigenetic changes. 

PMID- 23860797
TI  - Plant biotechnology for food security and bioeconomy.
AB  - This year is a special year for plant biotechnology. It was 30 years ago, on
      January 18 1983, one of the most important dates in the history of plant
      biotechnology, that three independent groups described Agrobacterium tumefaciens
      mediated genetic transformation at the Miami Winter Symposium, leading to the
      production of normal, fertile transgenic plants (Bevan et al. in Nature 304:184
      187, 1983; Fraley et al. in Proc Natl Acad Sci USA 80:4803-4807, 1983; Herrera
      Estrella et al. in EMBO J 2:987-995, 1983; Vasil in Plant Cell Rep 27:1432-1440,
      2008). Since then, plant biotechnology has rapidly advanced into a useful and
      valuable tool and has made a significant impact on crop production, development
      of a biotech industry and the bio-based economy worldwide. 

PMID- 23860798
TI  - Patient preference of ranibizumab treatment regimen for neovascular age-related
      macular degeneration - monthly injections versus pro re nata.
AB  - PURPOSE: To identify preference of treatment regimen in patients with anti-VEGF
      therapy for neovascular age-related macular degeneration (AMD) in real life.
      METHODS: A cross-sectional study was conducted in 200 patients receiving
      ranibizumab therapy on a pro re nata regimen with monthly controls. One hundred
      and twenty-four patients were recruited in a tertiary health care clinic, and 76
      patients were recruited in a private practice. Patients were asked to respond to
      a 14-item questionnaire covering items such as treatment burden and preference
      for treatment: either monthly injections or pro re nata. RESULTS: Mean time under
      anti-VEGF treatment was 33.7 months, and the mean number of intravitreal
      injections was 17.7. Despite a high treatment burden in 60.3 % of patients, there
      was an acceptance rate for monthly examinations or injections of 93 %. The
      proportion of patients who favoured a PRN regimen was 53.0 %, whereas 37.9 % of
      patients favoured continuous injections. Major concern was recurrent disease
      activity in 54.5 %. CONCLUSION: We identified two groups of patients of
      considerable size who would prefer either monthly injections or as-required.
      Overall, there was a high acceptance rate despite a high treatment burden.
      Nevertheless, efforts should be undertaken to improve examination and injection
      procedures and to consider the patient's preference for a treatment regimen.

PMID- 23860799
TI  - Fasting therapy in China: modification and future development.

PMID- 23860800
TI  - Glucan HBP-A increase type II collagen expression of chondrocytes in vitro and
      tissue engineered cartilage in vivo.
AB  - OBJECTIVE: Although chondroprotective activities have been documented for
      polysaccharides, the potential target of different polysaccharide may differ. The
      study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer
      culture and chondrocytes-alginate hydrogel constructs in vivo, especially on the
      expression of type II collagen. METHODS: Chondrocytes isolated from rabbit
      articular cartilage were cultured and verified by immunocytochemical staining of
      type II collagen. Chondrocyte viability was assessed after being treated with HBP
      A in different concentrations. Morphological status of chondrocytes-alginate
      hydrogel constructs in vitro was observed by scanning electron microscope (SEM).
      The constructs were treated with HBP-A and then injected to nude mice
      subcutaneously. Six weeks after transplantation, the specimens were observed
      through transmission electron microscopy (TEM). The mRNA expressions of
      disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTs-5),
      aggrecan and type II collagen in both monolayer culture and constructs were
      determined by real time polymerase chain reaction (PCR). The expression of type
      II collagen and matrix metalloproteinases-3 (MMP-3) in chondrocyte monolayer
      culture was also tested through Western blot and enzyme linked immunosorbent
      assay (ELISA), respectively. RESULTS: MMP-3 secretion and ADAMTs-5 mRNA
      expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration. In
      morphological study, there were significant appearance of collagen in those
      constructs treated by HBP-A. Accordingly, in both chondrocyte monolayer culture
      and chondrocytes-alginate hydrogel constructs, the expression of type II collagen
      was increased significantly in HBP-A group when compared with control group
      (P<0.001). CONCLUSIONS: The study documented that the potential pharmacological
      target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered
      cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP
      3, ADAMTs-5, and increasing of type II collagen expression.

PMID- 23860801
TI  - Percutaneous management of postoperative bile leaks with an ethylene vinyl
      alcohol copolymer (Onyx).
AB  - PURPOSE: The management of postoperative bile leakage is challenging especially
      if the leak rises from the cut surface of the liver and endoscopic treatment
      fails. Percutaneous transhepatic treatment of bile leaks with biliary drainage is
      accepted but often requires long-term placement of the drains and is associated
      with treatment failures. This series evaluates selective embolization of bile
      ducts with an ethylene vinyl alcohol copolymer (Onyx) in patients with
      postoperative bile leaks as an alternative treatment option. MATERIALS AND
      METHODS: Between January and September 2012, five consecutive patients with
      persistent postoperative bile leaks underwent percutaneous transhepatic Onyx
      application and were analyzed regarding procedural management, complications and
      success rates. RESULTS: The persistent bile leaks were situated at the cystic
      stump (after cholecystectomy, n = 2), at the cut surface of the liver (after
      extended liver resection, n = 2) and at the surface of the liver after surgical
      exploration and perihepatic abscess (n = 1). Bile drainage alone (endoscopic or
      percutaneous) failed in all patients and open redo-surgery was deemed potentially
      harmful. Bilomas were externally drained in all patients before Onyx application.
      For the closure of bile leaks, Onyx was injected through a microcatheter in a
      previously built coil nest to keep Onyx in place. All bile leaks were initially
      closed immediately. In the 2nd week after Onyx embolization, 2 patients showed
      recurrent small bile leaks without clinical symptoms. In the 4th week after Onyx
      application, all leaks were closed. No complications occurred. CONCLUSION: All
      leaking bile ducts were initially closed immediately after Onyx application. In
      the 2nd week after Onyx application, 2 patients showed small bile leaks without
      clinical symptoms. All leaks were closed in the 4th week after Onyx application.

PMID- 23860802
TI  - Correlation of the apparent diffusion coefficient (ADC) with the standardized
      uptake value (SUV) in hybrid 18F-FDG PET/MRI in non-small cell lung cancer
      (NSCLC) lesions: initial results.
AB  - PURPOSE: To compare the apparent diffusion coefficient (ADC) in non-small cell
      lung cancer lesions with standardized uptake values (SUV) derived from combined
      18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging
      (FDG-PET/MRI) and those derived from FDG-PET/CT. MATERIALS AND METHODS: In 18
      consecutive patients with histologically proven NSCLC (17 men, 1 woman; mean age,
      61 +/- 12 years), whole-body FDG-PET/MRI was performed after whole-body FDG
      PET/CT. Regions of interest (ROI) encompassing the entire primary tumor were
      drawn into FDG-PET/CT and FDG-PET/MR images to determine the maximum and mean
      standardized uptake value (SUVmax; SUVmean) and into ADC parameter maps to assess
      mean ADC values. Pearson's correlation coefficients were calculated to compare
      SUV and ADC values. RESULTS: The SUVmax of NSCLC was 12.3 +/- 4.8 [mean +/-SD],
      and the SUVmean was 7.2 +/- 2.8 as assessed by FDG-PET/MRI. The SUVmax and
      SUVmean derived from FDG-PET/CT and FDG-PET/MRI correlated well (R = 0.93; p <
      0.001 and R = 0.92; p < 0.001, respectively). The ADCmean of the pulmonary tumors
      was 187.9 +/- 88.8 * 10-5 mm2/s [mean +/- SD]. The ADCmean exhibited a
      significant inverse correlation with the SUVmax (R = -0.72; p < 0.001) as well as
      with the SUVmean assessed by FDG-PET/MRI (R = -0.71; p < 0.001). CONCLUSION: This
      simultaneous PET/MRI study corroborates the assumed significant inverse
      correlation between increased metabolic activity on FDG-PET and restricted
      diffusion on DWI in NSCLC.Citation Format:

PMID- 23860803
TI  - Synthesis and biological activity of divalent ligands based on 3-deoxy-4
      thiolactose, an isosteric analogue of lactose.
AB  - We report here the synthesis of divalent ligands containing 3-deoxy-4
      thiolactose. This thiodisaccharide has been synthesized using the Michael
      addition of beta-1-thiogalactose to the alpha,beta-unsaturated system of sugar
      derived dihydropyranones, followed by the reduction of the remaining carbonyl
      group. We were able to control the configuration (S) of the stereocenter linked
      to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high
      temperature or by isomerization during the reduction of the 2-ulose
      thiodisaccharide with NaBH4/THF. The energy profile for this reaction on a model
      compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was
      functionalized with a terminal alkyne, which was coupled to azide-containing
      sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The
      final products were competitive inhibitors of E. coli beta-galactosidase in the
      micromolar range. Their binding affinities to peanut agglutinin (PNA) were
      determined by isothermal calorimetry, which showed a clear decrease in the Ka
      values for monovalent derivatives compared to lactose. This report contributes to
      establishing the role of a particular hydroxyl group of lactose in sugar-protein
      recognition processes. 

PMID- 23860805
TI  - An opportunity to ensure high-quality melanoma care through the use of a
      preoperative treatment algorithm.
AB  - BACKGROUND: Studies have demonstrated variable adherence to published melanoma
      treatment guidelines. Payers have used algorithms to preapprove certain tests and
      treatments. Our objective was to develop a preoperative treatment assessment
      algorithm to ensure patients with melanoma receive recommended care. METHODS: A
      treatment algorithm was developed using existing guidelines. Records of patients
      presenting with melanoma between September 2010 and May 2012 were reviewed.
      Surgical care was classified as having been adherent or nonadherent with the
      guideline-based algorithm. The algorithm was incorporated into a Web site for
      preoperative treatment verification. RESULTS: A treatment algorithm was developed
      on the basis of three critical pieces of preoperative data: Breslow thickness,
      presence of adverse primary tumor prognostic factors, and regional lymph node
      metastases. Treatment options included wide local excision (WLE), sentinel lymph
      node biopsy (SLNB), and completion/formal lymph node dissection. Of 328 patients
      evaluated, 316 (96%) were treated according to the guideline-based algorithm.
      Causes of variation from predicted treatment included patient preference, severe
      comorbidities, difficult tumor location, and uncertain depth. All departures (n =
      12) were in clinically node-negative patients: six patients did not undergo SLNB
      as indicated, and six underwent SLNB that was not concordant with the algorithm.
      An algorithm-embedded Web site was designed for preoperative verification of
      planned procedures. CONCLUSIONS: As a proof of principle, an algorithm was
      developed to preoperatively verify that proposed melanoma treatments are
      concordant with established guidelines. These three pieces of information could
      be required during precertification, and nonconcordant treatment plans could
      prompt a peer-to-peer discussion. After additional pilot testing, the algorithm
      could offer a novel approach for quality improvement and provide a preoperative,
      prospective safeguard to ensure high-quality care for melanoma patients.

PMID- 23860807
TI  - Highlighting the important effect of systemic lupus erythematosus on platelet
      count of critically ill patients.

PMID- 23860806
TI  - Prevalence and prognostic value of acute cor pulmonale and patent foramen ovale
      in ventilated patients with early acute respiratory distress syndrome: a
      multicenter study.
AB  - PURPOSE: We sought to determine the prevalence of and factors associated with
      acute cor pulmonale (ACP) and patent foramen ovale (PFO) at the early phase of
      acute respiratory distress syndrome (ARDS), and to assess their relation with
      mortality. METHODS: In this prospective multicenter study, 200 patients submitted
      to protective ventilation for early moderate to severe ARDS [PaO2/F(I)O2: 115 +/-
      39 with F(I)O2: 1; positive end-expiratory pressure (PEEP): 10.6 +/- 3.1 cmH2O]
      underwent transthoracic (TTE) and transesophageal echocardiography (TEE) <48 h
      after admission. Echocardiograms were independently interpreted by two experts.
      Factors associated with ACP, PFO, and 28-day mortality were identified using
      multivariate regression analysis. RESULTS: TEE depicted ACP in 45/200 patients
      [22.5%; 95% confidence interval (CI) 16.9-28.9%], PFO in 31 patients (15.5%; 95%
      CI 10.8-21.3%), and both ACP and PFO in 9 patients (4.5%; 95% CI 2.1-8.4%). PFO
      shunting was small and intermittent in 27 patients, moderate and consistent in 4
      patients, and large or extensive in no instances. PaCO2 >60 mmHg was strongly
      associated with ACP [odds ratio (OR) 3.70; 95% CI 1.32-10.38; p = 0.01]. No
      factor was independently associated with PFO, with only a trend for age (OR 2.07;
      95% CI 0.91-4.72; p = 0.08). Twenty-eight-day mortality was 23%. Plateau pressure
      (OR 1.15; 95% CI 1.05-1.26; p < 0.01) and air leaks (OR 5.48; 95% CI 1.30-22.99;
      p = 0.02), but neither ACP nor PFO, were independently associated with outcome.
      CONCLUSIONS: TEE screening allowed identification of ACP in one-fourth of
      patients submitted to protective ventilation for early moderate to severe ARDS.
      PFO shunting was less frequent and never large or extensive. ACP and PFO were not
      related to outcome.

PMID- 23860808
TI  - Complications of operative treatment of clavicle fractures in a Level I Trauma
      Center.
AB  - Traditionally, the belief is that the clavicle heals readily and with
      nonoperative treatment. Since evidence suggests that many clavicles benefit from
      operative care, the aim of this study was to find the incidence of complications
      after operative treatment of clavicle fractures. This retrospective study
      includes 56 patients (41 male and 15 female) who were treated operatively for
      clavicle fractures between 2010 and 2012. The indications were displacement more
      than 20 mm, comminution, tenting of the skin, floating shoulder, and open
      fractures. Seventy-five percent of the fractures occurred in the midshaft and 25
      % in the lateral third of the clavicle. There were no fractures of the medial
      third. The midshaft fractures were either plated with 3.5 mm reconstruction
      plates or anatomical locking plates. For internal fixation of the lateral
      fractures, we used acromioclavicular hook plates. The mean follow-up period was
      4.6 months (range 1.0-28.0). Three patients did not participate in the follow-up.
      There were 12 patients with complications (21 %). Five of them required
      reoperations. Two patients were reoperated due to clavicle nonunions, two
      patients due to traumatic refracture of the plated clavicle, and one because of
      pain caused by the plate. Four cases developed superficial infections, and there
      was one patient with a deep tissue infection. None of the patients showed signs
      of neurovascular impairment postoperatively. None of the patients complained
      about decreased range of motion or loss of muscle strength postoperatively.
      Plating of clavicle fractures is a procedure that results in lower rates of
      malunion, nonunion, and functional impairment compared with nonoperative
      treatment. Nonetheless, one case in ten has a complicated course. Attention to
      technique and careful follow-up may prevent these problems. 

PMID- 23860810
TI  - Surgical options for lumbosacral fusion: biomechanical stability, advantage,
      disadvantage and affecting factors in selecting options.
AB  - PURPOSE: Numerous surgical procedures and instrumentation techniques for
      lumbosacral fusion (LSF) have been developed. This is probably because of its
      high mechanical demand and unique anatomy. Surgical options include anterior
      column support (ACS) and posterior stabilization procedures. Biomechanical
      studies have been performed to verify the stability of those options. The options
      have their own advantage but also disadvantage aspects. This review article
      reports the surgical options for lumbosacral fusion, their biomechanical
      stability, advantages/disadvantages, and affecting factors in option selection.
      METHODS: Review of literature. CONCLUSION: LSF has lots of options both for ACS
      and posterior stabilization procedures. Combination of posterior stabilization
      procedures is an option. Furthermore, combinations of ACS and posterior
      stabilization procedures are other options. It is difficult to make a
      recommendation or treatment algorithm of LSF from the current literature.
      However, it is important to know all aspects of the options and decision-making
      of surgical options for LSF needs to be tailored for each patient, considering
      factors such as biomechanical stress and osteoporosis.

PMID- 23860809
TI  - Trabecular metal screw implanted for avascular necrosis of the femoral head may
      complicate subsequent arthroplasty surgery.
AB  - A trabecular metal screw has been suggested to treat avascular osteonecrosis of
      the femoral head. Non-surgical management with partial weight bearing can only be
      selected for early stages and very small lesions. Even in such cases, it has been
      proven to be ineffective in 80-90 % of patients. Conversely, the results with
      trabecular metal implants are not always clinically satisfactory, and some
      patients can show emerging pain and activity limitations that could require
      conversion to a total hip arthroplasty. Hereby we report the results of 6
      patients who underwent this implant and describe the histopathology of the bone
      at the femoral neck and to speculate on the causes of complications encountered
      during arthroplasty surgery. The necrosis was stopped in 1 case, and 5 hips
      showed disease progression. Two protrusions of the screw apex were observed. In
      one case, rupture of the greater trochanter during prosthesis implant occurred.
      After trabecular metal implants for avascular osteonecrosis, some patients can
      require conversion to a total hip arthroplasty. Two patients had an
      intraoperative fracture with detachment of the greater trochanter that required
      wiring. Complications related to implant removal can be encountered, and the
      orthopedic surgeon should be aware of removal techniques.

PMID- 23860811
TI  - Interaction of the heart and its close and distant neighbours: report of the
      Meeting of the ESC Working Groups Myocardial Function and Cellular Biology.

PMID- 23860813
TI  - Complications from laser-assisted liposuction performed by noncore practitioners.
AB  - Liposuction is one of the most commonly performed aesthetic surgery procedures in
      the United States, and most plastic surgeons perform suction-assisted, ultrasound
      assisted, or power-assisted liposuction. The past decade has seen a growing
      interest in laser-assisted liposuction (LAL) and the proposed advantages of
      traditional liposuction methods. However, it is performed by a minority of
      plastic surgeons. In fact, many LAL providers are not trained in aesthetic
      practice, and many offer LAL as their only body-contouring procedure. When only
      one method of body contouring is available to a provider, it may lead to
      inappropriate patient selection with associated poor outcomes. This report
      discusses the use of laser liposuction in body contouring and the demographics of
      those performing liposuction, including LAL. Complications from laser-assisted
      liposuction performed by noncore practitioners are illustrated.

PMID- 23860812
TI  - Critical roles of junctophilin-2 in T-tubule and excitation-contraction coupling
      maturation during postnatal development.
AB  - AIMS: Emerging evidence indicates a critical role for junctophilin-2 (JP2) in T
      tubule integrity and assembly of cardiac dyads in adult ventricular myocytes. In
      the postnatal stage, one of the critical features of myocyte maturation is
      development of the T-tubule system, though the mechanisms remain poorly
      understood. In this study, we aim to determine whether JP2 is required for normal
      cardiac T-tubule maturation. METHODS AND RESULTS: Using in situ confocal imaging
      of intact murine hearts, we found T-tubules were absent in both left- and right
      ventricular myocytes at postnatal Day 8 and did not appear until Day 10.
      Quantification of T-tubule structural integrity using the T-tubule power
      (TT(power)) index revealed a progressive increase in TT(power) between postnatal
      Days 10 and 19. By postnatal Day 19, TT(power) was similar to that in adult
      murine cardiomyocytes, indicative of a nearly matured T-tubule network. JP2
      levels increased dramatically during development, reaching levels observed in
      adult hearts by postnatal Day 14. Deficiency of JP2, using a mouse model in which
      a JP2-specific shRNA is expressed during embryonic development, severely impaired
      T-tubule maturation, with equivalent decreases in the left- and right-ventricular
      TT(power). We also detected a gradual increase in the density of transverse but
      not longitudinal tubules during development, and JP2 deficiency abolished the
      increase in the density of transverse elements. Alterations in T-tubules caused
      significant reduction in Ca(2+) transient amplitude and marked increase in Ca(2+)
      release dyssynchrony, Ca(2+) alternans, and spontaneous Ca(2+) waves, leading to
      contractile failure. CONCLUSION: Our data identify a critical role for JP2 in T
      tubule and excitation-contraction coupling maturation during development.

PMID- 23860814
TI  - Reduction of antitragal projection as an adjunct to correction of prominent ears.

PMID- 23860815
TI  - Poly Implant Prothese (PIP) incidence of device failure and capsular contracture:
      a retrospective comparative analysis.
AB  - BACKGROUND: The Medicine and Healthcare Products Regulatory Agency in the United
      Kingdom issued a Medical Device Alert (MDA/2010/025) through a press release on
      31 March 2010 for clinicians not to use the Poly Implant Prothese (PIP) implant.
      METHODS: Data were collected to analyze PIP and non-PIP implant failures as well
      as rates of capsular contracture between August 2008 and August 2012. Relevant
      data were retrieved for 143 patients with PIP (group A) and non-PIP (group B)
      implants. RESULTS: Group A (PIP): A total of 65 patients had PIP implants
      removed. The mean patient age was 37.1 +/- 8.1 years (range 24-53 years). The
      mean duration of the implant was 7.2 +/- 2.5 years (range 2-12 years), and the
      mean preoperative implant size was 327.1 +/- 69.6 ml (range 255-495 ml). Of the
      implants in 65 patients, 18 (27.7 %) were damaged, and of the 64 patients with
      recorded capsular contractures, 16 (25 %) presented with grades 3 and 4 capsular
      contractures. Group B (non-PIP): A total of 79 patients had non-PIP implants
      removed. The mean patient age was 34.4 +/- 8.0 years (range 19-54 years). The
      mean implantation time was 5.8 +/- 3.9 years (range 0.2-26 years), and the mean
      preoperative implant size was 348.2 +/- 79.0 ml (range 175-555 ml). Of the 79
      patients, 6 had ruptured implants (7.6 %) and 21 (26.6 %) presented with grades 3
      and 4 capsular contractures. There were no statistically significant differences
      in mean patient age (p = 0.046), preoperative size of the implants (p = 0.095),
      duration of the implantation (p = 0.08), or grades 3 and 4 capsular contractures
      (p = 0.830). The incidence of implant rupture was significantly higher with the
      PIP implants than with the non-PIP implants (p = 0.01). CONCLUSION: The PIP
      implants were more prone to rupture than the other implants, although the
      incidence of clinical capsular contracture (grades 3 and 4) was not increased.

PMID- 23860816
TI  - The use of synthetic mesh in reconstructive, revision, and cosmetic breast
      surgery.
AB  - BACKGROUND: Recent evidence suggests that the use of acellular dermal matrices in
      prosthetic breast reconstruction, revision, or augmentation may be associated
      with an increased risk of complications. In this article we report our results of
      a potential alternative, using a new long-term resorbable synthetic matrix in
      these cases. METHODS: A retrospective study was performed evaluating 11 primary
      breast reconstructions (19 breasts), 43 secondary reconstructions (77 breasts), 3
      augmentation/augmentation mastopexys (6 breasts), and 5 mastopexys (10 breasts)
      in 62 patients using TIGR((r)) Matrix Surgical Mesh. RESULTS: Follow-up ranged
      from 9.4 to 26.1 months with an average follow-up of 16.5 months. Average age was
      54 years. The number of patients who had prior radiation was 9 (14.5 %). Four
      patients (6.5 %) were smokers. Postoperative breast complications included
      necrosis of two flaps (1.8 %), two seromas requiring drainage (1.8 %), four
      infection/extrusions (3.6 %), two relapses of inframammary fold/malposition (1.8
      %), and two with rippling (1.8 %). Other complications included six cases of
      asymmetry that required a corrective procedure. In a variety of breast surgery
      cases very good aesthetic results were achieved. CONCLUSION: The long-term
      absorbable synthetic matrix, TIGR((r)) Matrix Surgical Mesh, shows potential when
      used as temporary reinforcement in patients undergoing breast reconstruction or
      breast surgery revisions and in primary aesthetic procedures, and it appears to
      be a viable alternative to the use of acellular dermal matrices.

PMID- 23860817
TI  - Use of osseocartilaginous paste graft for refinement of the nasal dorsum in
      rhinoplasty.
AB  - In both primary and secondary rhinoplasty, establishment or refinement of nasal
      dorsal aesthetic lines is of paramount importance. Many different techniques used
      to create a cosmetically acceptable nasal dorsum have been published. The
      material to be used in nasal dorsal contouring should create a harmonic contour
      and should be easily shaped, long-lasting, and resistant to infection. Resection
      of the hump yields an osseocartilaginous complex as a single unit when an
      osteotome is used. Use of a rasp gives a good amount of fragmented material
      comprising bone, cartilage, soft tissues, and blood. The authors used this
      material as a paste graft to refine the nasal dorsum in rhinoplasty and
      retrospectively evaluated the outcomes. A retrospective chart review of 77
      patients who underwent this procedure between 2003 and 2009 was performed. The
      follow-up period ranged from 22 to 40 months (median, 28 months). The
      postoperative evaluations included clinical examination and digital photographic
      documentation. The satisfaction of each patient was assessed with a questionnaire
      completed at the 12th postoperative month. The described graft, which combines
      the advantages of cartilage and bone, was shown to be clinically durable. This
      combination also results in an ideal texture and consistency for molding due to
      its diced form. The texture of this graft enables the surgeon to give a final
      shape to the nasal dorsum bimanually. In this study, a paste graft was shown to
      be a versatile and reliable composite material for nasal dorsal contouring and
      refinement.

PMID- 23860818
TI  - Device-assisted transepidermal delivery of cosmeceuticals: a new way to enhance
      aesthetic procedures?

PMID- 23860819
TI  - Discussion: tuberous breast: revised classification and a new hypothesis for its
      development.

PMID- 23860820
TI  - Interlocking circumareolar suture with undyed polyamide thread: a personal
      experience.
AB  - In plastic breast surgery, the interlocking areolar suture has gained wide
      popularity since its introduction in 2007 by Hammond and colleagues. The
      interlocking circumareolar suture plays its role in the setting of circumareolar
      excisions to achieve a durable areola shaping and to prevent scar
      widening/hypertrophy and areola spreading/distortion. This study retrospectively
      reviewed 49 breasts that underwent interlocking suture after July 2011 for both
      aesthetic and reconstructive indications. For the suturing, 3-0 undyed polyamide
      thread with a straight cutting needle (Dafilon; B. Braun Melsungen AG, Melsungen,
      Germany) was used. This suture material was preferred to Gore-Tex reported by
      Hammond and colleagues because it is undyed without any microporous
      configuration, more wieldy, and less expensive. All 49 breasts showed good
      results in terms of areola shaping and diameter control as well as good scar
      quality during a mean follow-up period of 12 months (range 2-18 months) (Fig. 2).
      No infection, suture extrusion, skin fistula, or granuloma were experienced. The
      suture was not visible at all, and the patients did not report its palpability.
      However, at careful examination, the thread resulted slightly palpable.

PMID- 23860821
TI  - One-staged silicone implant breast reconstruction following bilateral nipple
      sparing prophylactic mastectomy in patients at high risk for breast cancer.

PMID- 23860822
TI  - Management of prepubertal gynecomastia in two monozygotic twins with Peutz
      Jeghers syndrome: from aromatase inhibitors to subcutaneous mastectomy.
AB  - BACKGROUND: Prepubertal gynecomastia is characterized by the presence of palpable
      uni- or bilateral breast tissue in boys without other signs of sexual maturation.
      It may be the endocrine expression of rare syndromes such as Peutz-Jeghers
      syndrome (PJS). This study aimed to evaluate the effectiveness of anastrozole and
      to describe an innovative surgical approach. METHODS: This report presents twins
      with PJS, bilateral prepubertal gynecomastia, and testicular multifocal
      calcifications. Both twins were treated with anastrozole for 2 years. After
      finishing treatment, both were followed before subcutaneous mastectomy was
      performed by the "modified" Webster technique. RESULTS: Growth velocity decreased
      and gynecomastia diminished during anastrozole treatment. After discontinuation
      of therapy due to a sharp reduction in growth velocity, both twins showed
      regrowth of gynecomastia, with painful and strained breasts. A significant
      reduction in breast volume with glandular removal was achieved. CONCLUSIONS: The
      findings of this study showed a multidisciplinary approach to prepubertal
      gynecomastia due to the synergy of pediatricians, radiologists, and plastic
      surgeons. The follow-up evaluation after the anastrozole treatment showed it to
      be an efficacious medical treatment, as an alternative to orchidectomy, to
      control the effects of circulating estrogens. Moreover, the results observed in
      the patients confirmed the validity and feasibility of the "modified" Webster
      technique in terms of aesthetic and functional results, patient satisfaction, and
      absence of complications.

PMID- 23860823
TI  - Safety and effectiveness of biphasic insulin aspart 30 in different age-groups:
      a1chieve sub-analysis.
AB  - INTRODUCTION: Effective management of type 2 diabetes requires sustained glycemic
      control over many years, which can be particularly challenging for elderly
      people. This sub-analysis of the A1chieve study evaluated the clinical safety and
      effectiveness of biphasic insulin aspart 30 in 3 age-groups (<=40, >40-65, and
      >65 years) of previously insulin-experienced and insulin-naive people with type 2
      diabetes. METHODS: A1chieve was an international, multicenter, prospective, open
      label, non-interventional, 24-week study in people with type 2 diabetes who had
      been receiving anti-diabetes medication before starting, or switching to, therapy
      with biphasic insulin aspart 30, insulin detemir or insulin aspart (alone or in
      combination) in routine clinical practice. This sub-analysis evaluated clinical
      safety and effectiveness of biphasic insulin aspart 30 (+/-oral glucose-lowering
      drugs) in different age-groups. RESULTS: Data on 40,122 participants were
      included. In all age-groups, the proportion of participants experiencing any
      hypoglycemia, major hypoglycemia or nocturnal hypoglycemia was significantly
      reduced from baseline, except for the following in insulin-naive patients: a
      significant increase in any hypoglycemia in patients aged >65 years; no change in
      any hypoglycemia, major hypoglycemia, and nocturnal hypoglycemia in patients aged
      >40-65, <=40, and >65 years, respectively. Significant improvements at 24 weeks
      vs. baseline were observed in insulin-experienced and insulin-naive participants
      for: glycated hemoglobin (change from baseline ranged from -1.8% to -2.4%);
      fasting plasma glucose (from -3.0 to -4.3 mmol/l); post-breakfast post-prandial
      plasma glucose (from -4.1 to -6.5 mmol/l); and health-related quality of life
      (HRQoL). Sixteen serious adverse drug reactions were reported. CONCLUSION: After
      24-week treatment with biphasic insulin aspart 30, all age-groups of insulin
      experienced and insulin-naive patients experienced significantly improved
      glycemic control and HRQoL; incidence of hypoglycemia was generally reduced. The
      tolerability and effectiveness of biphasic insulin aspart 30 may benefit all age
      groups.

PMID- 23860825
TI  - Mid-term follow-up of stenting in chronic mesenteric ischaemia: a review of six
      cases.
AB  - BACKGROUND: Chronic mesenteric angina is a rare condition with high morbidity and
      mortality, which occurs due to stenosis or occlusion in the mesenteric vessels
      commonly due to atherosclerosis. Typically, patients present with worsening
      postprandial abdominal pain, chronic weight loss and fear of food. The condition
      can be treated by surgical bypass, but also by percutaneous transluminal
      angioplasty and stenting of the affected mesenteric arteries. AIM: To assess the
      mid-term outcomes in patients treated by endovascular stenting for chronic
      mesenteric ischaemia (CMI). METHODS: Six patients were treated for symptomatic
      CMI. In total, six severely stenosed vessels were stented including the superior
      mesenteric artery (n = 5) and coeliac artery (n = 1). A retrospective review of
      these patients was performed with end points including symptom recurrence, major
      morbidity and mortality. The mean follow-up was 16.5 months (range 5-28 months).
      RESULTS: Initial clinical success was observed in all six patients. Four patients
      were clinically asymptomatic, but died within 18 months after the procedure from
      other conditions. One patient suffered from recurrence of symptoms. Only one
      patient died as a consequence of mesenteric artery re-stenosis. CONCLUSION:
      Stenting of mesenteric vessels has shown excellent early and mid-term clinical
      success in selected patients. Though no direct comparison with open
      revascularization surgery was performed in this case series, technical and mid
      term clinical success is promising.

PMID- 23860826
TI  - Acquisition technology research of EEG and related physiological signals under
      +Gz acceleration.
AB  - BACKGROUND: With the continuous improvement of maneuvering performance of modern
      high-performance aircraft, the protection problem of flight personnel under high
      G acceleration, the development as well as research on monitoring system and the
      equipment for human physiological signals processing which include
      electroencephalogram (EEG) have become more and more important. Due to the
      particularity of +Gz experimental conditions, the high-risk of human experiments
      and the great difficulty of dynamic measurement, there is little research on the
      synchronous acquisition technology of EEG and related physiological signals under
      +Gz acceleration environment. METHODS: We propose a framework to execute human
      experiments using the three-axial high-performance human centrifuge, develop
      reasonable operation mode and design a new experimental research method for EEG
      signal acquisition and variation characteristics on three-axial high-performance
      human centrifuge under the environment of +Gz acceleration. We also propose to
      build the synchronous real-time acquisition plan of EEG, electrocardiogram, brain
      blood pressure, ear pulse and related physiological signals under centrifuge +Gz
      acceleration with different equipments and methods. RESULTS: The good profiles of
      EEG, heart rate, brain blood pressure and ear pulse are obtained and analyzed
      comparatively. In addition, the FMS hop-by-hop continuous blood pressure and
      hemodynamic measurement system Portapres are successfully applied to the
      ambulatory blood pressure measure under centrifuge +Gz acceleration environment.
      CONCLUSIONS: The proposed methods establish the basis and have an important
      guiding significance for follow-up experiment development, EEG features spectral
      analysis and correlation research of all signals.

PMID- 23860827
TI  - Continuous ECS-indicated recording of the proton-motive charge flux in leaves.
AB  - Technical features and examples of application of a special emitter-detector
      module for highly sensitive measurements of the electrochromic pigment absorbance
      shift (ECS) via dual-wavelength (550-520 nm) transmittance changes (P515) are
      described. This device, which has been introduced as an accessory of the
      standard, commercially available Dual-PAM-100 measuring system, not only allows
      steady-state assessment of the proton motive force (pmf) and its partitioning
      into DeltapH and DeltaPsi components, but also continuous recording of the
      overall charge flux driven by photosynthetic light reactions. The new approach
      employs a double-modulation technique to derive a continuous signal from the
      light/dark modulation amplitude of the P515 signal. This new, continuously
      measured signal primarily reflects the rate of proton efflux via the ATP
      synthase, which under quasi-stationary conditions corresponds to the overall rate
      of proton influx driven by coupled electron transport. Simultaneous measurements
      of charge flux and CO2 uptake as a function of light intensity indicated a close
      to linear relationship in the light-limited range. A linear relationship between
      these two signals was also found for different internal CO2 concentrations,
      except for very low CO2, where the rate of charge flux distinctly exceeded the
      rate of CO2 uptake. Parallel oscillations in CO2 uptake and charge flux were
      induced by high CO2 and O2. The new device may contribute to the elucidation of
      complex regulatory mechanisms in intact leaves. 

PMID- 23860829
TI  - Construction of a controllable beta-carotene biosynthetic pathway by
      decentralized assembly strategy in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae is an important platform organism for the synthesis of a
      great number of natural products. However, the assembly of controllable and
      genetically stable heterogeneous biosynthetic pathways in S. cerevisiae still
      remains a significant challenge. Here, we present a strategy for reconstructing
      controllable multi-gene pathways by employing the GAL regulatory system. A set of
      marker recyclable integrative plasmids (pMRI) was designed for decentralized
      assembly of pathways. As proof-of-principle, a controllable beta-carotene
      biosynthesis pathway (~16 kb) was reconstructed and optimized by repeatedly using
      GAL10-GAL1 bidirectional promoters with high efficiency (80-100%). By controling
      the switch time of the pathway, production of 11 mg/g DCW of total carotenoids
      (72.57 mg/L) and 7.41 mg/g DCW of beta-carotene was achieved in shake-flask
      culture. In addition, the engineered yeast strain exhibited high genetic
      stability after 20 generations of subculture. The results demonstrated a
      controllable and genetically stable biosynthetic pathway capable of increasing
      the yield of target products. Furthermore, the strategy presented in this study
      could be extended to construct other pathways in S. cerevisisae.

PMID- 23860828
TI  - Photosynthetic electron transport and specific photoprotective responses in wheat
      leaves under drought stress.
AB  - The photosynthetic responses of wheat (Triticum aestivum L.) leaves to different
      levels of drought stress were analyzed in potted plants cultivated in growth
      chamber under moderate light. Low-to-medium drought stress was induced by
      limiting irrigation, maintaining 20 % of soil water holding capacity for 14 days
      followed by 3 days without water supply to induce severe stress. Measurements of
      CO2 exchange and photosystem II (PSII) yield (by chlorophyll fluorescence) were
      followed by simultaneous measurements of yield of PSI (by P700 absorbance
      changes) and that of PSII. Drought stress gradually decreased PSII electron
      transport, but the capacity for nonphotochemical quenching increased more slowly
      until there was a large decrease in leaf relative water content (where the
      photosynthetic rate had decreased by half or more). We identified a substantial
      part of PSII electron transport, which was not used by carbon assimilation or by
      photorespiration, which clearly indicates activities of alternative electron
      sinks. Decreasing the fraction of light absorbed by PSII and increasing the
      fraction absorbed by PSI with increasing drought stress (rather than assuming
      equal absorption by the two photosystems) support a proposed function of PSI
      cyclic electron flow to generate a proton-motive force to activate
      nonphotochemical dissipation of energy, and it is consistent with the observed
      accumulation of oxidized P700 which causes a decrease in PSI electron acceptors.
      Our results support the roles of alternative electron sinks (either from PSII or
      PSI) and cyclic electron flow in photoprotection of PSII and PSI in drought
      stress conditions. In future studies on plant stress, analyses of the
      partitioning of absorbed energy between photosystems are needed for interpreting
      flux through linear electron flow, PSI cyclic electron flow, along with
      alternative electron sinks. 

PMID- 23860830
TI  - [Parkour--"art of movement" and its injury risk].
AB  - INTRODUCTION: Parkour sport is the playfully breaching of obstacles originally
      not created to get from A to B in the fastest manner. There have been only few
      publications on injuries in this young and trendy sport mainly performed in urban
      areas. The aim of this study is to analyse parkour-related acute injuries and
      their factors. METHODS: For the retrospective cross-sectional study, a total of n
      = 266 traceurs (m: n = 255, w: n = 11) completed anonymized online
      questionnaires. RESULTS: On average, each traceur sustained 1.9 injuries per
      sport career/year, or 5.5 injuries/1000 h training, respectively. The upper
      extremity was the most affected body region (58 %), followed by the lower
      extremity (27 %), head and the back. An increase of injuries from proximal to
      distal was observed in the upper extremity. However, for the lower extremity it
      was the opposite. Of all injuries, the most common were skin abrasions (70.3 %).
      Muscle injuries were observed in 13.1 % of the traceurs, followed by dislocations
      (6.1 %), and soft tissue (e. g., ligaments, tendons) injuries (5.3 %). Passive
      precautionary measures were abandoned by the majority of the traceurs (88 %).
      Landing belonged to the movement elements resulting in most of the injuries (61
      %), followed by supportive and static efforts of the arms (10.7 %).
      Overestimation (23 %) as well as misjudging the situation (20 %) were the most
      common causes. CONCLUSION: Other than expected, parkour is an urban movement
      style with most of the injuries being neither severe nor common despite the lack
      of precautionary measures. Localisation and type of injuries reflect the
      characteristic movement elements. There is a need for further investigations to
      allow a more differentiated analysis in order to develop injury prevention
      concepts.

PMID- 23860831
TI  - Anomalies in the motion dynamics of long-flagella mutants of Chlamydomonas
      reinhardtii.
AB  - Chlamydomonas reinhardtii has long been used as a model organism in studies of
      cell motility and flagellar dynamics. The motility of the well-conserved '9+2'
      axoneme in its flagella remains a subject of immense curiosity. Using high-speed
      videography and morphological analyses, we have characterized long-flagella
      mutants (lf1, lf2-1, lf2-5, lf3-2, and lf4) of C. reinhardtii for biophysical
      parameters such as swimming velocities, waveforms, beat frequencies, and swimming
      trajectories. These mutants are aberrant in proteins involved in the regulation
      of flagellar length and bring about a phenotypic increase in this length. Our
      results reveal that the flagellar beat frequency and swimming velocity are
      negatively correlated with the length of the flagella. When compared to the wild
      type, any increase in the flagellar length reduces both the swimming velocities
      (by 26-57%) and beat frequencies (by 8-16%). We demonstrate that with no apparent
      aberrations/ultrastructural deformities in the mutant axonemes, it is this
      increased length that has a critical role to play in the motion dynamics of C.
      reinhardtii cells, and, provided there are no significant changes in their
      flagellar proteome, any increase in this length compromises the swimming velocity
      either by reduction of the beat frequency or by an alteration in the waveform of
      the flagella. 

PMID- 23860833
TI  - Stage-structured cannibalism with delay in maturation and harvesting of an adult
      predator.
AB  - A three-dimensional stage-structured predator-prey model is proposed and analyzed
      to study the effect of predation and cannibalism of the organisms at the highest
      trophic level with non-constant harvesting. Time lag in maturation of the
      predator is introduced in the system and conditions for local asymptotic
      stability of steady states are derived. The length of the delay preserving the
      stability is also estimated. Moreover, it is shown that the system undergoes a
      supercritical Hopf bifurcation when the maturation time lag crosses a certain
      critical value. Computer simulations have been carried out to illustrate various
      analytical results. 

PMID- 23860832
TI  - Nano breathers and molecular dynamics simulations in hydrogen-bonded chains.
AB  - Non-linear localization phenomena in biological lattices have attracted a
      steadily growing interest and their existence has been predicted in a wide range
      of physical settings. We investigate the non-linear proton dynamics of a hydrogen
      bonded chain in a semi-classical limit using the coherent state method combined
      with a Holstein-Primakoff bosonic representation. We demonstrate that even a weak
      inherent discreteness in the hydrogen-bonded (HB) chain may drastically modify
      the dynamics of the non-linear system, leading to instabilities that have no
      analog in the continuum limit. We suggest a possible localization mechanism of
      polarization oscillations of protons in a hydrogen-bonded chain through
      modulational instability analysis. This mechanism arises due to the neighboring
      proton-proton interaction and coherent tunneling of protons along hydrogen bonds
      and/or around heavy atoms. We present a detailed analysis of modulational
      instability, and highlight the role of the interaction strength of neighboring
      protons in the process of bioenergy localization. We perform molecular dynamics
      simulations and demonstrate the existence of nanoscale discrete breather (DB)
      modes in the hydrogen-bonded chain. These highly localized and long-lived non
      linear breather modes may play a functional role in targeted energy transfer in
      biological systems. 

PMID- 23860834
TI  - Attraction and repulsion of spiral waves by inhomogeneity of conduction
      anisotropy--a model of spiral wave interaction with electrical remodeling of
      heart tissue.
AB  - Various forms of heart disease are associated with remodeling of the heart
      muscle, which results in a perturbation of cell-to-cell electrical coupling.
      These perturbations may alter the trajectory of spiral wave drift in the heart
      muscle. We investigate the effect of spatially extended inhomogeneity of
      transverse cell coupling on the spiral wave trajectory using a simple active
      media model. The spiral wave was either attracted or repelled from the center of
      inhomogeneity as a function of cell excitability and gradient of the cell
      coupling. High levels of excitability resulted in an attraction of the wave to
      the center of inhomogeneity, whereas low levels resulted in an escape and
      termination of the spiral wave. The spiral wave drift velocity was related to the
      gradient of the coupling and the initial position of the wave. In a diseased
      heart, a region of altered transverse coupling corresponds with local gap
      junction remodeling that may be responsible for stabilization-destabilization of
      spiral waves and hence reflect potentially important targets in the treatment of
      heart arrhythmias. 

PMID- 23860836
TI  - Analysis of recruitment and industrial human resources management for optimal
      productivity in the presence of the HIV/AIDS epidemic.
AB  - The aim of this paper is to analyze the recruitment effects of susceptible and
      infected individuals in order to assess the productivity of an organizational
      labor force in the presence of HIV/AIDS with preventive and HAART treatment
      measures in enhancing the workforce output. We consider constant controls as well
      as time-dependent controls. In the constant control case, we calculate the basic
      reproduction number and investigate the existence and stability of equilibria.
      The model is found to exhibit backward and Hopf bifurcations, implying that for
      the disease to be eradicated, the basic reproductive number must be below a
      critical value of less than one. We also investigate, by calculating sensitivity
      indices, the sensitivity of the basic reproductive number to the model's
      parameters. In the time-dependent control case, we use Pontryagin's maximum
      principle to derive necessary conditions for the optimal control of the disease.
      Finally, numerical simulations are performed to illustrate the analytical
      results. The cost-effectiveness analysis results show that optimal efforts on
      recruitment (HIV screening of applicants, etc.) is not the most cost-effective
      strategy to enhance productivity in the organizational labor force. Hence, to
      enhance employees' productivity, effective education programs and strict
      adherence to preventive measures should be promoted. 

PMID- 23860835
TI  - Intrinsic microtubule GTP-cap dynamics in semi-confined systems: kinetochore
      microtubule interface.
AB  - In order to quantify the intrinsic dynamics associated with the tip of a GTP-cap
      under semi-confined conditions, such as those within a neuronal cone and at a
      kinetochore-microtubule interface, we propose a novel quantitative concept of
      critical nano local GTP-tubulin concentration (CNLC). A simulation of a rate
      constant of GTP-tubulin hydrolysis, under varying conditions based on this
      concept, generates results in the range of 0-420 s(-1). These results are in
      agreement with published experimental data, validating our model. The major
      outcome of this model is the prediction of 11 random and distinct outbursts of
      GTP hydrolysis per single layer of a GTP-cap. GTP hydrolysis is accompanied by an
      energy release and the formation of discrete expanding zones, built by less
      stable, skewed GDP-tubulin subunits. We suggest that the front of these expanding
      zones within the walls of the microtubule represent soliton-like movements of
      local deformation triggered by energy released from an outburst of hydrolysis. We
      propose that these solitons might be helpful in addressing a long-standing
      question relating to the mechanism underlying how GTP-tubulin hydrolysis controls
      dynamic instability. This result strongly supports the prediction that large
      conformational movements in tubulin subunits, termed dynamic transitions, occur
      as a result of the conversion of chemical energy that is triggered by GTP
      hydrolysis (Sataric et al., Electromagn Biol Med 24:255-264, 2005). Although
      simple, the concept of CNLC enables the formulation of a rationale to explain the
      intrinsic nature of the "push-and-pull" mechanism associated with a kinetochore
      microtubule complex. In addition, the capacity of the microtubule wall to produce
      and mediate localized spatio-temporal excitations, i.e., soliton-like bursts of
      energy coupled with an abundance of microtubules in dendritic spines supports the
      hypothesis that microtubule dynamics may underlie neural information processing
      including neurocomputation (Hameroff, J Biol Phys 36:71-93, 2010; Hameroff,
      Cognit Sci 31:1035-1045, 2007; Hameroff and Watt, J Theor Biol 98:549-561, 1982).

PMID- 23860837
TI  - Analysis of tissue condition based on interaction between inorganic and organic
      matter in cuttlefish bone.
AB  - The absorption properties of an inner layer of cuttlefish bone were measured
      using a transmission terahertz time-domain spectrometer in a band from
      approximately 0.1 to 4 THz. For oriented samples, an absorption peak related to
      the behavior of calcium carbonate appeared at approximately 2 THz. The peak
      magnitude and frequency depended on the direction of the incident terahertz
      electric field, indicating that calcium carbonate crystals constituting the inner
      layer were oriented in a certain direction. The absorbance of a sample heated to
      350  degrees C for 0 to 2 h to remove organic matter tended to decrease with
      heating time in the oriented direction, while the peak frequency shifted to
      higher frequencies. Furthermore, we showed that the peak frequency depended on
      the interaction area within the unheated sample and we thus obtained a two
      dimensional image reflecting crystal regularity inside the cuttlefish bone from
      the spectral data at each position. 

PMID- 23860838
TI  - Effects of a type I antifreeze protein (AFP) on the melting of frozen AFP and
      AFP+solute aqueous solutions studied by NMR microimaging experiment.
AB  - The effects of a type I AFP on the bulk melting of frozen AFP solutions and
      frozen AFP+solute solutions were studied through an NMR microimaging experiment.
      The solutes studied include sodium chloride and glucose and the amino acids
      alanine, threonine, arginine, and aspartic acid. We found that the AFP is able to
      induce the bulk melting of the frozen AFP solutions at temperatures lower than 0 
      degrees C and can also keep the ice melted at higher temperatures in the
      AFP+solute solutions than those in the corresponding solute solutions. The latter
      shows that the ice phases were in super-heated states in the frozen AFP+solute
      solutions. We have tried to understand the first experimental phenomenon via the
      recent theoretical prediction that type I AFP can induce the local melting of ice
      upon adsorption to ice surfaces. The latter experimental phenomenon was explained
      with the hypothesis that the adsorption of AFP to ice surfaces introduces a less
      hydrophilic water-AFP-ice interfacial region, which repels the ionic/hydrophilic
      solutes. Thus, this interfacial region formed an intermediate chemical potential
      layer between the water phase and the ice phase, which prevented the transfer of
      water from the ice phase to the water phase. We have also attempted to understand
      the significance of the observed melting phenomena to the survival of organisms
      that express AFPs over cold winters. 

PMID- 23860839
TI  - Modeling transport of a pulse of radiolabeled organelles in a Drosophila unipolar
      motor neuron.
AB  - Based on published experimental evidence, this paper develops a model for the
      transport of a pulse of radiolabeled organelles in a unipolar Drosophila motor
      neuron. In particular, since published data indicate that no microtubules (MTs)
      travel from the primary neurite into the dendrite, it is investigated how
      organelles are transported into the dendrite. Analytical solutions describing
      concentrations of kinesin- and dynein-driven organelles in the primary neurite,
      axon, and dendrite are obtained. The effects of increasing the width of the pulse
      and increasing the rate of organelle transition rate from the kinesin-driven to
      the dynein-driven state are investigated. 

PMID- 23860842
TI  - Effects of aerobic exercise training on large-conductance Ca(2+)-activated K (+)
      channels in rat cerebral artery smooth muscle cells.
AB  - PURPOSE: Large-conductance Ca(2+)-activated K(+) (BKCa) channels provide a
      negative feedback that regulates vascular tone in the brain circulation. This
      study investigated the effects of aerobic exercise on gating properties of BKCa
      channels in rat cerebral artery. METHODS: Rats were subjected to moderate
      intensity exercise at low (EX-3d/w) and high (EX-5d/w) training volume on a motor
      driven treadmill, and compared with age-matched sedentary animals (SED). Inside
      out (I/O) patch clamp recording was performed to measure gating properties of the
      BKCa channel. RESULTS: Aerobic exercise induced a reduction in heart rate and
      body weight in both training groups. Exercise increased the channel activity,
      which was more pronounced in EX-5d/w than that in EX-3d/w group. Kinetic analysis
      revealed that (1) the contribution of short open states was elevated and the
      duration of both short and long open states were extended by exercising in EX
      3d/w; (2) Ex-3d/w had no significant change on conformation of close states; (3)
      EX-3d/w increased the mean open time without changing mean closed time; (4) EX
      5d/w increased both the contribution and duration of long open states; (5) EX
      5d/w increased channel mean open time while decreased mean closed time.
      CONCLUSION: The results suggest that regular aerobic exercise may enhance BKCa
      channel activity in cerebral arterial myocytes by changing its biophysical
      properties, and the electrical remolding induced by exercise may be training
      volume-dependent.

PMID- 23860843
TI  - beta(3R3)-Peptides: design and synthesis of novel peptidomimetics and their self
      assembling properties at the air-water interface.
AB  - In this study we present the design and synthesis of a novel class of
      peptidomimetics, the beta(3R3)-peptides. Via alternating directions of the amide
      bonds along beta-peptide sequences, beta(3R3)-peptides can potentially extend the
      structural space available to beta-peptidic foldamers. Detailed analysis at the
      air-water interface shows strand conformations and the formation of sheet
      assemblies with different degrees of crystallinity. Furthermore beta(3R3)
      peptides exhibit a high proteolytic stability thus making them an interesting new
      class of peptidomimetics for biomedical applications. 

PMID- 23860841
TI  - Blood pressure regulation VIII: resistance vessel tone and implications for a pro
      atherogenic conduit artery endothelial cell phenotype.
AB  - Dysfunction of the endothelium is proposed as the primary initiator of
      atherosclerotic peripheral artery disease, which occurs mainly in medium- to
      large-sized conduit arteries of the lower extremities (e.g., iliac, femoral,
      popliteal arteries). In this review article, we propose the novel concept that
      conduit artery endothelial cell phenotype is determined, in part, by
      microvascular tone in skeletal muscle resistance arteries through both changes in
      arterial blood pressure as well as upstream conduit artery shear stress patterns.
      First, we summarize the literature supporting the involvement of sympathetic
      nerve activity (SNA) and nitric oxide (NO) in the modulation of microvascular
      tone and arterial blood pressure. We then focus on the role of elevated blood
      pressure and shear stress profiles in modulating conduit artery endothelial cell
      phenotype. Last, we discuss findings from classic and emerging studies indicating
      that increased vascular resistance, as it occurs in the context of increased SNA
      and/or reduced NO bioavailability, is associated with greater oscillatory shear
      stress (e.g., increased retrograde shear) in upstream conduit arteries. The ideas
      put forth in this review set the stage for a new paradigm concerning the
      mechanistic link between increased microvascular tone and development of conduit
      artery endothelial dysfunction and thus increased risk for peripheral artery
      disease. Indeed, a vast amount of evidence supports the notion that excessive
      blood pressure and oscillatory shear stress are potent pro-atherogenic signals to
      the endothelium. 

PMID- 23860845
TI  - Biocatalysts for cascade reaction: porcine pancreas lipase (PPL)-catalyzed
      synthesis of bis(indolyl)alkanes.
AB  - A cascade reaction between aldehydes and indole catalyzed by lipase from porcine
      pancreas Type II (PPL) in solvent mixture at 50  degrees C was reported for the
      first time. Some control experiments had been designed to demonstrate that the
      PPL was responsible for the cascade reaction. After the optimization of the
      stepwise process, a series of bis(indolyl)alkanes were prepared in moderate to
      excellent yields under the catalysis of PPL. 

PMID- 23860846
TI  - Innovative approaches to the use of polyamines for DNA nanoparticle preparation
      for gene therapy.
AB  - Advances in genomic technologies, such as next generation sequencing and disease
      specific gene targeting through anti-sense, anti-gene, siRNA and microRNA
      approaches require the transport of nucleic acid drugs through the cell membrane.
      Membrane transport of DNA/RNA drugs is an inefficient process, and the
      mechanism(s) by which this process occurs is not clear. A pre-requisite for
      effective transport of DNA and RNA in cells is their condensation to
      nanoparticles of ~100 nm size. Although viral vectors are effective in gene
      therapy, the immune response elicited by viral proteins poses a major challenge.
      Multivalent cations, such as natural polyamines are excellent promoters of
      DNA/RNA condensation to nanoparticles. During the past 20 years, our laboratory
      has synthesized and tested several analogs of the natural polyamine, spermine,
      for their efficacy to provoke DNA condensation to nanoparticles. We determined
      the thermodynamics of polyamine-mediated DNA condensation, measured the
      structural specificity effects of polyamine analogs in facilitating the cellular
      uptake of oligonucleotides, and evaluated the gene silencing activity of DNA
      nanoparticles in breast cancer cells. Polyamine-complexed oligonucleotides showed
      a synergistic effect on target gene inhibition at the mRNA level compared to the
      use of polyamines and oligonucleotides as single agents. Ionic and structural
      specificity effects were evident in DNA condensation and cellular transportation
      effects of polyamines. In condensed DNA structures, correlation exists between
      the attractive and repulsive forces with structurally different polyamines and
      cobalt hexamine, indicating the existence of a common force in stabilizing the
      condensed structures. Future studies aimed at defining the mechanism(s) of DNA
      compaction and structural features of DNA nanoparticles might aid in the
      development of novel gene delivery vehicles.

PMID- 23860844
TI  - Assessing biological aging: the origin of deficit accumulation.
AB  - The health of individuals is highly heterogeneous, as is the rate at which they
      age. To account for such heterogeneity, we have suggested that an individual's
      health status can be represented by the number of health deficits (broadly
      defined by biological and clinical characteristics) that they accumulate. This
      allows health to be expressed in a single number: the frailty index (FI) is the
      ratio of the deficits present in a person to the total number of deficits
      considered (e.g. in a given database or experimental procedure). Changes in the
      FI characterize the rate of individual aging. The behavior of the FI is highly
      characteristic: it shows an age specific, nonlinear increase, (similar to
      Gompertz law), higher values in females, strong associations with adverse
      outcomes (e.g., mortality), and a universal limit to its increase (at FI ~0.7).
      These features have been demonstrated in dozens of studies. Even so, little is
      known about the origin of deficit accumulation. Here, we apply a stochastic
      dynamics framework to illustrate that the average number of deficits present in
      an individual is the product of the average intensity of the environmental
      stresses and the average recovery time. The age-associated increase in recovery
      time results in the accumulation of deficits. This not only explains why the
      number of deficits can be used to estimate individual differences in aging rates,
      but also suggests that targeting the recovery rate (e.g. by preventive or
      therapeutic interventions) will decrease the number of deficits that individuals
      accumulate and thereby benefit life expectancy. 

PMID- 23860847
TI  - Foldamers of beta-peptides: conformational preference of peptides formed by rigid
      building blocks. The first MI-IR spectra of a triamide nanosystem.
AB  - To determine local chirality driven conformational preferences of small
      aminocyclobutane-1-carboxylic acid derivatives, X-(ACBA) n -Y, their matrix
      isolation IR spectra were recorded and analyzed. For the very first time model
      systems of this kind were deposited in a frozen (~10 K) noble gas matrix to
      reduce line width and thus, the recorded sharp vibrational lines were analyzed in
      details. For cis-(S,R)-1 monomer two "zigzag" conformers composed of either a six
      or an eight-membered H-bonded pseudo ring was identified. For trans-(S,S)-2
      stereoisomer a zigzag of an eight-membered pseudo ring and a helical building
      unit were determined. Both findings are fully consistent with our computational
      results, even though the relative conformational ratios were found to vary with
      respect to measurements. For the dimers (S,R,S,S)-3 and (S,S,S,R)-4 as many as
      four different cis,trans and three different trans,cis conformers were localized
      in their matrix-isolation IR (MI-IR) spectra. These foldamers not only agree with
      the previous computational and NMR results, but also unambiguously show for the
      first time the presence of a structure made of a cis,trans conformer which links
      a "zigzag" and a helical foldamer via a bifurcated H-bond. The present work
      underlines the importance of MI-IR spectroscopy, applied for the first time for
      triamides to analyze the conformational pool of small biomolecules. We have shown
      that the local chirality of a beta-amino acid can fully control its backbone
      folding preferences. Unlike proteogenic alpha-peptides, beta- and especially
      (ACBA) n type oligopeptides could thus be used to rationally design and influence
      foldamer's structural preferences. 

PMID- 23860849
TI  - Transglutaminase-mediated macromolecular assembly: production of conjugates for
      food and pharmaceutical applications.
AB  - Various strategies have been explored in the last 20 years to modify the
      functional properties of proteins and, among these, protein/polymer conjugation
      resulted one of the most successful approaches. Thus, the surface modification of
      polypeptides of potential industrial interest by covalent attachment of different
      macromolecules is nowadays regarded as an extremely valuable technique to
      manipulate protein activities. Protein derivatives with a number of either
      natural or synthetic polymers, like different polysaccharides or polyethylene
      glycol, have been obtained by both chemical and enzymatic treatments, and in this
      context, the crosslinking enzyme transglutaminase is attracting an increasing
      attention as a simple and safe means for protein processing in vitro. In this
      short review, we summarized the most significant experimental findings
      demonstrating that a microbial form of the enzyme is an effective tool to obtain
      several biopolymer-based conjugates potentially useful for both food and
      pharmaceutical applications.

PMID- 23860850
TI  - Sleep characteristics and health-related quality of life among a national sample
      of American young adults: assessment of possible health disparities.
AB  - PURPOSE: The aim of the study is to examine the associations of sleep
      characteristics with health-related quality of life (HRQOL) and sleep health
      disparities among US young adults using national survey data. METHODS: The study
      sample consisted of 2,391 young adults aged 20-39 years from the National Health
      and Nutrition Examination Survey 2005-2008. HRQOL was assessed using the Centers
      for Disease Control and Prevention's HRQOL-4 scale. Multivariable logistic
      regression models were applied to evaluate the sleep-HRQOL associations.
      Stratified analyses were conducted to examine whether the associations varied by
      sociodemographic characteristics. RESULTS: Approximately 35.6 % of young adults
      slept <7 h, 41.9 % had insomnia, 4.4 % had sleep disorder, and 8.5 % had sleep
      apnea. More females had insomnia than males (48.6 vs. 35.9 %, P < 0.001). US-born
      young adults had more sleep disturbances than their foreign-born counterparts.
      Compared with those sleeping 7-8 h, the adjusted odds ratio of poor general
      health was 1.60 (95 % confidence interval, 1.08-2.35) for individuals sleeping 6
      7 h and 1.88 (1.23-2.86) for those sleeping <6 h. Similar results were found for
      low mental HRQOL and overall HRQOL. Insomnia, long sleep latency, troubling
      falling asleep, daytime sleepiness, and frequent sleeping pill use were
      significantly associated with low mental HRQOL and overall HRQOL. The
      associations between sleep disturbances and low HRQOL varied little by sex,
      race/ethnicity, and country of birth. CONCLUSIONS: Sleep disturbances are common
      among US young adults and are significantly associated with low HRQOL. Objective
      measures of sleep are warranted to confirm our findings.

PMID- 23860851
TI  - Individuality Normalization when Labeling with Isotopic Glycan Hydrazide Tags
      (INLIGHT): a novel glycan-relative quantification strategy.
AB  - The Individuality Normalization when Labeling with Isotopic Glycan Hydrazide Tags
      (INLIGHT) strategy for the sample preparation, data analysis, and relative
      quantification of N-linked glycans is presented. Glycans are derivatized with
      either natural (L) or stable-isotope labeled (H) hydrazide reagents and analyzed
      using reversed phase liquid chromatography coupled online to a Q Exactive mass
      spectrometer. A simple glycan ladder, maltodextrin, is first used to demonstrate
      the relative quantification strategy in samples with negligible analytical and
      biological variability. It is shown that after a molecular weight correction
      attributable to isotopic overlap and a post-acquisition normalization of the data
      to account for any systematic bias, a plot of the experimental H:L ratio versus
      the calculated H:L ratio exhibits a correlation of unity for maltodextrin samples
      mixed in different ratios. We also demonstrate that the INLIGHT approach can
      quantify species over four orders of magnitude in ion abundance. The INLIGHT
      strategy is further demonstrated in pooled human plasma, where it is shown that
      the post-acquisition normalization is more effective than using a single spiked
      in internal standard. Finally, changes in glycosylation are able to be detected
      in complex biological matrices, when spiked with a glycoprotein. The ability to
      spike in a glycoprotein and detect change at the glycan level validates both the
      sample preparation and data analysis strategy, making INLIGHT an invaluable
      relative quantification strategy for the field of glycomics. 

PMID- 23860852
TI  - Role of cationization and multimers formation for diastereomers differentiation
      by ion mobility-mass spectrometry.
AB  - Stereochemistry plays an important role in biochemistry, particularly in
      therapeutic applications. Indeed, enantiomers have different biological
      activities, which can have important consequences. Many analytical techniques
      have been developed in order to allow the identification and the separation of
      stereoisomers. Here, we focused our work on the study of small diastereomers
      using the coupling of traveling wave ion mobility and mass spectrometry (TWIMS
      MS) as a new alternative for stereochemistry study. In order to optimize the
      separation, the formation of adducts between diastereomers (M) and different
      alkali cations (X) was carried out. Thus, monomers [M + X](+) and multimers [2M +
      X](+) and [3M + X](+) ions have been studied from both experimental and
      theoretical viewpoints. Moreover, it has been shown that the study of the
      multimer [2Y + M + Li](+) ion, in which Y is an auxiliary diastereomeric ligand,
      allows the diastereomers separation. The combination of cationization, multimers
      ions formation, and IM-MS is a novel and powerful approach for the diastereomers
      identification. Thus, by this technique, diastereomers can be identified although
      they present very close conformations in gaseous phase. This work presents the
      first TWIMS-MS separation of diastereomers, which present very close collision
      cross section thanks to the formation of multimers and the use of an auxiliary
      diastereomeric ligand. 

PMID- 23860854
TI  - Pattern transfer during deposition and fixation of oligomeric bisphenol A on pre
      structured copper surfaces.
AB  - Pattern transfer during deposition of oligomeric bisphenol A (OBA) on pre
      structured Cu surfaces is investigated by means of a combined experimental
      computational approach. Aiming for quantitative prediction of experiments, as
      characterized by atomic force microscopy (AFM), we explore the capabilities of
      stochastic rate equations to quantitatively account for the spatio-temporal
      evolution of surface topography. While surface diffusion and deposition noise
      constitute the main mechanisms, pattern transfer is affected by the inclusion of
      retardation in the interface potential, which appears to be necessary beyond a
      critical initial surface slope. In addition, routes for successful surface
      fixation by cross-linking are also demonstrated, which may pave the way for
      further technological use. 

PMID- 23860855
TI  - Sparganosis of upper extremity in subcutaneous and intramuscular layers.

PMID- 23860856
TI  - Ultrasound emissions: thermal and mechanical indices.

PMID- 23860857
TI  - Ultrasonographic assessment of tendon thickness, Doppler activity and bony spurs
      of the elbow in patients with lateral epicondylitis and healthy subjects: a
      reliability and agreement study.
AB  - PURPOSE: Tennis elbow, also known as lateral epicondylitis (LE), is a common
      disorder often assessed by ultrasound. The aim of this study was to evaluate the
      ultrasonographic outcomes and methods used in LE research and clinical practice.
      MATERIALS AND METHODS: This study was designed as an intra- and interobserver
      reliability and agreement study. Ultrasonographic examination of the common
      extensor tendon of the elbow was performed. The intraobserver study examined
      tendon thickness twice in 20 right elbows from 20 healthy individuals at an
      interval of 7 to 12 days. The interobserver study examined tendon thickness,
      color Doppler activity, and bony spurs in 18 right elbows in 9 healthy
      individuals and 9 patients with LE. Two trained rheumatologists performed the
      interobserver examinations with the same scanner on the same day. The main
      outcomes were intra- and interclass correlation (ICC) and agreement. RESULTS: In
      the intraobserver study, the ICC with regard to tendon thickness ranged from 0.76
      to 0.81, depending on the measurement techniques used. The agreement ranged from
      0.06 to 0.13 mm. In the interobserver study, the tendon thickness ICC ranged from
      0.45 to 0.65 and the agreement ranged from -0.17 to 0.13 mm. The ICC for color
      Doppler activity was 0.93, with agreement in 14/18 (78 %) of the cases. A perfect
      reliability was demonstrated for bony spurs, with an ICC of 1 and exact agreement
      in 18/18 (100 %) of the cases. CONCLUSION: Good to excellent reliability was
      obtained for all measurements. The ultrasonographic techniques evaluated in this
      trial can be recommended for use in both research and clinical practice.

PMID- 23860858
TI  - Potential use of contrast-enhanced ultrasound (CEUS) in the detection of
      metastatic superficial lymph nodes in melanoma patients.
AB  - PURPOSE: Malignant melanoma represents a significant and growing public health
      burden worldwide. Ultrasonography is the most useful diagnostic modality for
      regional lymph nodal staging. Because any focal areas of cortical lobulation or
      thickening-swelling should also be considered as a sign of metastases, we are
      going to report the usefulness of contrast-enhanced ultrasonography (CEUS) in the
      differential diagnosis of benign or malignant lymph nodes in patients with
      malignant melanoma based on blood stream patterns and investigate the diagnostic
      capability. PATIENTS AND METHODS: After the excision of cutaneous melanoma with
      positive excision margins but with negative sentinel lymph node, 540 patients
      underwent US of superficial lymph nodes. The inclusion criteria for CEUS
      consisted of both major signs (absence of the echogenic hilus, round shape, and
      peripheral capsular vascularity) and minor ones (the presence of focal cortical
      thickening). The diagnostic capability was evaluated by comparing the cytological
      findings with the enhancement pattern on CEUS.  RESULTS: US in combination with
      CEUS correctly classified 534/540 patients. CEUS applied to lymph nodes with
      focal cortical thickening on grayscale US confirmed great sensitivity (0.98) and
      specificity (0.99) but above all, it showed a markedly improved accuracy of 0.99.
      The likelihood ratios confirmed the good performance of the methods used.
      CONCLUSION: CEUS increases the diagnostic accuracy of US in the differential
      diagnosis of benign and malignant LNs but it also allows us, when possible, to
      avoid unnecessary invasive operations such as LN FNAC. Moreover, CEUS may guide
      FNAC in the case of focal cortical thickening on the basis of hypoperfusion, with
      a reduction in the number of false negatives and much earlier detection of nodal
      metastatic foci.

PMID- 23860859
TI  - Multidisciplinary management of recurrent chordomas.
AB  - OPINION STATEMENT: The management of recurrent chordomas are clinically
      challenging because of its relentless nature. Local therapy, whether surgery or
      radiation, are important considerations since local progression of disease
      results in significant morbidity and locally aggressive treatment is often
      required. Stereotactic radiosurgery, shown to be very effective for
      radioresistant histologies, may be an important radiotherapeutic approach for
      recurrent tumors. Ultimately, the treatment of recurrent chordoma is palliative
      in intent, thus, enthusiasm for improving local control must be tempered against
      the possible impact of treatment on quality of life. Judicious use of
      radiotherapy and surgery can often provide meaningful palliation and local
      control of recurrences. Systemic treatment options, particularly with targeted
      molecules have great potential for chordomas in the recurrent setting, as the
      risk of disseminated disease is higher. The development of tools to help assess
      potential targets for drug therapy will be crucial. The incorporation of locally
      aggressive therapy and effective systemic therapy will be critical for the
      successful management of recurrent chordomas. At present, there is a paucity of
      published data regarding salvage therapy. Nonetheless, advances in surgical,
      medical, and radiation oncology are providing new avenues of research and
      potentially may have significant impact upon successful salvage treatment.

PMID- 23860861
TI  - Novel insights on magadiite disaggregation: a multitechnique study on thermal
      stability.
AB  - Disaggregated magadiite was obtained through ion-exchange in acidic media from
      magadiite intercalated in the synthesis with cetyltrimethylamonium cations. The
      combination of Soxhlet extraction and ultrasound during the procedure resulted in
      different morphology and different properties when compared with the pristine
      material, as observed by SEM. Thermal and surface properties studies performed by
      VT-XRD, TG, VT-FTIR, HETCOR SS-NMR, and N2 physisorption show that disaggregated
      magadiite presents a basal space of 1.35 nm and that [SiO4] entities of adjacent
      magadiite silicate layers connect during ion-exchange under ultrasound. Despite
      these bonding events, the surface area increased from 20-26 m(2) g(-1) in CTA
      magadiite to 55-72 m(2) g(-1) in disaggregated magadiite. 

PMID- 23860860
TI  - Design of short membrane selective antimicrobial peptides containing tryptophan
      and arginine residues for improved activity, salt-resistance, and
      biocompatibility.
AB  - Antimicrobial peptides (AMPs) kill microbes by non-specific membrane
      permeabilization, making them ideal templates for designing novel peptide-based
      antibiotics that can combat multi-drug resistant pathogens. For maximum efficacy
      in vivo and in vitro, AMPs must be biocompatible, salt-tolerant and possess broad
      spectrum antimicrobial activity. These attributes can be obtained by rational
      design of peptides guided by good understanding of peptide structure-function.
      Toward this end, this study investigates the influence of charge and
      hydrophobicity on the activity of tryptophan and arginine rich decamer peptides
      engineered from a salt resistant human beta-defensin-28 variant. Mechanistic
      investigations of the decamers with detergents mimicking the composition of
      bacterial and mammalian membrane, reveal a correlation between improved
      antibacterial activity and the increase in tryptophan and positive residue
      content, while keeping hemolysis low. The potent antimicrobial activity and high
      cell membrane selective behavior of the two most active decamers, D5 and D6, are
      attributed to an optimum peptide charge to hydrophobic ratio bestowed by
      systematic arginine and tryptophan substitution. D5 and D6 show surface
      localization behavior with binding constants of 1.86 * 10(8) and 2.6 * 10(8)  M(
      1) , respectively, as determined by isothermal calorimetry measurements. NMR
      derived structures of D5 and D6 in SDS detergent micelles revealed proximity of
      Trp and Arg residues in an extended structural scaffold. Such potential cation-pi
      interactions may be critical in cell permeabilization of the AMPs. The
      fundamental characterization of the engineered decamers provided in this study
      improves the understanding of structure-activity relationship of short arginine
      tryptophan rich AMPs, which will pave the way for future de novo design of potent
      AMPs for therapeutic and biomedical applications.

PMID- 23860862
TI  - 3D pure inorganic framework based on polymolybdovanadate possessing photoelectric
      properties.
AB  - The first 3D pure inorganic framework based on heteropolymolybdate anion
      [V2Mo16O58](10-) has been synthesized and its photoelectric properties
      demonstrated. 

PMID- 23860863
TI  - Spectroscopic properties of electrochemically populated electronic states in
      nanostructured TiO2 films: anatase versus rutile.
AB  - A thorough characterization of nanostructured materials under application
      relevant conditions is a prerequisite for elucidating the interplay between their
      physicochemical nature and their functional properties in practical applications.
      Here, we use a spectroelectrochemical approach to study the population of
      electronic states in different types of nanostructured anatase and rutile TiO2
      films in contact with an aqueous electrolyte. The spectroscopic properties of the
      two polymorphs were addressed under Fermi level control in the energy range
      between the fundamental absorption threshold and the onset of lattice absorption
      (3.3-0.1 eV). The results evidence the establishment of an equilibrium between
      localized Ti(3+) centers absorbing in the vis/NIR and shallow (e(-))(H(+)) traps
      absorbing in the MIR upon electron accumulation in anatase electrodes. The
      absence of the MIR-active (e(-))(H(+)) traps on all rutile electrodes points to a
      crystal structure-dependent electron population in the films. 

PMID- 23860864
TI  - Electromagnetic navigation provides high accuracy for transcoracoid
      transclavicular drilling.
AB  - PURPOSE: A novel radiation-free electromagnetic navigation system (ENS)-based
      method was developed, and its feasibility and accuracy for transclavicular
      transcoracoid drilling procedures were evaluated in an experimental setting.
      METHODS: Sixteen arthroscopically assisted electromagnetic navigated
      transcoracoid-transclavicular drilling procedures with subsequent TightRope
      device implantation were performed on eight human cadavers. Post-operative
      fluoroscopy and CT-scan analysis were acquired to determine tunnel placement
      accuracy. Optimal tunnel placement was defined as both the coracoid entry and
      exit point of the tunnel localized in the centre position of the coracoid base
      without cortical breach or fracture. RESULTS: Successful tunnel placement was
      accomplished in all 16 cases. The mean overall operation time was 30.3 +/- 5.0
      min. Regarding the coracoid exit point, 15 of 16 tunnels (93.8%) were localized
      in the desired base-centre position. During the navigated drilling procedure, no
      misguidance of the drill requiring directional readjustments or restarts
      occurred. No cortical breach, no fractures and no complications occurred.
      CONCLUSIONS: The electromagnetically navigated transcoracoid-transclavicular
      drilling procedure used in this study demonstrated high targeting accuracy,
      required no intraoperative radiographs, was associated with no complications and
      provided user-friendliness.

PMID- 23860865
TI  - Special issue on physical virology.

PMID- 23860866
TI  - The icosahedral RNA virus as a grotto: organizing the genome into stalagmites and
      stalactites.
AB  - There are two important problems in the assembly of small, icosahedral RNA
      viruses. First, how does the capsid protein select the viral RNA for packaging,
      when there are so many other candidate RNA molecules available? Second, what is
      the mechanism of assembly? With regard to the first question, there are a number
      of cases where a particular RNA sequence or structure--often one or more stem
      loops--either promotes assembly or is required for assembly, but there are others
      where specific packaging signals are apparently not required. With regard to the
      assembly pathway, in those cases where stem-loops are involved, the first step is
      generally believed to be binding of the capsid proteins to these "fingers" of the
      RNA secondary structure. In the mature virus, the core of the RNA would then
      occupy the center of the viral particle, and the stem-loops would reach outward,
      towards the capsid, like stalagmites reaching up from the floor of a grotto
      towards the ceiling. Those viruses whose assembly does not depend on protein
      binding to stem-loops could have a different structure, with the core of the RNA
      lying just under the capsid, and the fingers reaching down into the interior of
      the virus, like stalactites. We review the literature on these alternative
      structures, focusing on RNA selectivity and the assembly mechanism, and we
      propose experiments aimed at determining, in a given virus, which of the two
      structures actually occurs.

PMID- 23860867
TI  - Evolution of nanoparticle-induced distortion on viral polyhedra.
AB  - Morphological changes in the polyhedra of the Bombyx mori L. nuclear polyhedrosis
      virus (BmNPV), a baculovirus causing the deadly grasserie disease in silkworms,
      brought about by mixing with lipophilically capped amorphous silica nanoparticles
      (LASN, average size 10 +/- 2 nm) were studied with scanning electron microscopy
      (SEM) and Fourier transform infrared (FTIR) spectroscopy. SEM shows that the
      regular octagonal polyhedra facets are replaced by a larger number of newly
      formed irregular ones. The average number of facets reveals a nonlinear growth
      pattern with nanoparticle (NP) concentration, where an initial linear region ends
      in a plateau. IR bands corresponding to vibration modes of the capping show (a) a
      saturation of the area under the band with NP concentration, indicating a
      correlation with attachment to viral polyhedra and (b) a narrowing of the band
      per NP from the linear to the plateau portions of the distortion curve,
      suggesting non-equilibrium and equilibrium situations, respectively.

PMID- 23860868
TI  - Modeling and simulation of the mechanical response from nanoindentation test of
      DNA-filled viral capsids.
AB  - Viruses can be described as biological objects composed mainly of two parts: a
      stiff protein shell called a capsid, and a core inside the capsid containing the
      nucleic acid and liquid. In many double-stranded DNA bacterial viruses (aka
      phage), the volume ratio between the liquid and the encapsidated DNA is
      approximately 1:1. Due to the dominant DNA hydration force, water strongly
      mediates the interaction between the packaged DNA strands. Therefore, water that
      hydrates the DNA plays an important role in nanoindentation experiments of DNA
      filled viral capsids. Nanoindentation measurements allow us to gain further
      insight into the nature of the hydration and electrostatic interactions between
      the DNA strands. With this motivation, a continuum-based numerical model for
      simulating the nanoindentation response of DNA-filled viral capsids is proposed
      here. The viral capsid is modeled as large- strain isotropic hyper-elastic
      material, whereas porous elasticity is adopted to capture the mechanical response
      of the filled viral capsid. The voids inside the viral capsid are assumed to be
      filled with liquid, which is modeled as a homogenous incompressible fluid. The
      motion of a fluid flowing through the porous medium upon capsid indentation is
      modeled using Darcy's law, describing the flow of fluid through a porous medium.
      The nanoindentation response is simulated using three-dimensional finite element
      analysis and the simulations are performed using the finite element code Abaqus.
      Force-indentation curves for empty, partially and completely DNA-filled capsids
      are directly compared to the experimental data for bacteriophage lambda. Material
      parameters such as Young's modulus, shear modulus, and bulk modulus are
      determined by comparing computed force-indentation curves to the data from the
      atomic force microscopy (AFM) experiments. Predictions are made for pressure
      distribution inside the capsid, as well as the fluid volume ratio variation
      during the indentation test. 

PMID- 23860869
TI  - Polymorphism of DNA conformation inside the bacteriophage capsid.
AB  - Double-stranded DNA bacteriophage genomes are packaged into their icosahedral
      capsids at the highest densities known so far (about 50 % w:v). How the molecule
      is folded at such density and how its conformation changes upon ejection or
      packaging are fascinating questions still largely open. We review cryo-TEM
      analyses of DNA conformation inside partially filled capsids as a function of the
      physico-chemical environment (ions, osmotic pressure, temperature). We show that
      there exists a wide variety of DNA conformations. Strikingly, the different
      observed structures can be described by some of the different models proposed
      over the years for DNA organisation inside bacteriophage capsids: either spool
      like structures with axial or concentric symmetries, or liquid crystalline
      structures characterised by a DNA homogeneous density. The relevance of these
      conformations for the understanding of DNA folding and unfolding upon ejection
      and packaging in vivo is discussed.

PMID- 23860870
TI  - Statistical analysis of sizes and shapes of virus capsids and their resulting
      elastic properties.
AB  - From the analysis of sizes of approximately 130 small icosahedral viruses we find
      that there is a typical structural capsid protein, having a mean diameter of 5 nm
      and a mean thickness of 3 nm, with more than two thirds of the analyzed capsid
      proteins having thicknesses between 2 nm and 4 nm. To investigate whether, in
      addition to the fairly conserved geometry, capsid proteins show similarities in
      the way they interact with one another, we examined the shapes of the capsids in
      detail. We classified them numerically according to their similarity to sphere
      and icosahedron and an interpolating set of shapes in between, all of them
      obtained from the theory of elasticity of shells. In order to make a unique and
      straightforward connection between an idealized, numerically calculated shape of
      an elastic shell and a capsid, we devised a special shape fitting procedure, the
      outcome of which is the idealized elastic shape fitting the capsid best. Using
      such a procedure we performed statistical analysis of a series of virus shapes
      and we found similarities between the capsid elastic properties of even very
      different viruses. As we explain in the paper, there are both structural and
      functional reasons for the convergence of protein sizes and capsid elastic
      properties. Our work presents a specific quantitative scheme to estimate
      relatedness between different proteins based on the details of the (quaternary)
      shape they form (capsid). As such, it may provide an information complementary to
      the one obtained from the studies of other types of protein similarity, such as
      the overall composition of structural elements, topology of the folded protein
      backbone, and sequence similarity.

PMID- 23860871
TI  - Langevin dynamics simulation of DNA ejection from a phage.
AB  - We have performed Langevin dynamics simulations of a coarse-grained model of
      ejection of dsDNA from Phi29 phage. Our simulation results show significant
      variations in the local ejection speed, consistent with experimental observations
      reported in the literature for both in vivo and in vitro systems. In efforts to
      understand the origin of such variations in the local speed of ejection, we have
      investigated the correlations between the local ejection kinetics and the
      packaged structures created at various motor forces and chain flexibility. At
      lower motor forces, the packaged DNA length is shorter with better organization.
      On the other hand, at higher motor forces typical of realistic situations, the
      DNA organization inside the capsid suffers from significant orientational
      disorder, but yet with long orientational correlation times. This in turn leads
      to lack of registry between the direction of the DNA segments just to be ejected
      and the direction of exit. As a result, a significant amount of momentum transfer
      is required locally for successful exit. Consequently, the DNA ejection
      temporarily slows down exhibiting pauses. This slowing down occurs at random
      times during the ejection process, completely determined by the particular
      starting conformation created by prescribed motor forces. In order to augment our
      inference, we have additionally investigated the ejection of chains with
      deliberately changed persistence length. For less inflexible chains, the demand
      on the occurrence of large momentum transfer for successful ejection is weaker,
      resulting in more uniform ejection kinetics. While being consistent with
      experimental observations, our results show the nonergodic nature of the ejection
      kinetics and call for better theoretical models to portray the kinetics of genome
      ejection from phages. 

PMID- 23860872
TI  - Strongly correlated electrostatics of viral genome packaging.
AB  - The problem of viral packaging (condensation) and ejection from viral capsid in
      the presence of multivalent counterions is considered. Experiments show divalent
      counterions strongly influence the amount of DNA ejected from bacteriophage. In
      this paper, the strong electrostatic interactions between DNA molecules in the
      presence of multivalent counterions is investigated. It is shown that experiment
      results agree reasonably well with the phenomenon of DNA reentrant condensation.
      This phenomenon is known to cause DNA condensation in the presence of tri- or
      tetra-valent counterions. For divalent counterions, the viral capsid confinement
      strongly suppresses DNA configurational entropy, therefore the correlation
      between divalent counterions is strongly enhanced causing similar effect.
      Computational studies also agree well with theoretical calculations. 

PMID- 23860873
TI  - Knotting of linear DNA in nano-slits and nano-channels: a numerical study.
AB  - The amount and type of self-entanglement of DNA filaments is significantly
      affected by spatial confinement, which is ubiquitous in biological systems.
      Motivated by recent advancements in single DNA molecule experiments based on
      nanofluidic devices and by the introduction of algorithms capable of detecting
      knots in open chains, we investigate numerically the entanglement of linear, open
      DNA chains confined inside nano-slits. The results regard the abundance, type,
      and length of occurring knots and are compared with recent findings for DNA
      inside nano-channels. In both cases, the width of the confining region, D, spans
      the 30 nm-1 MUm range and the confined DNA chains are 1-4 MUm long. It is found
      that the knotting probability is maximum for slit widths in the 70-100 nm range.
      However, over the considered DNA contour lengths, the maximum incidence of knots
      remains below 20%, while for channel confinement it tops 50%. Further differences
      of the entanglement are seen for the average contour length of the knotted
      region, which drops significantly below D ~100 nm for channel-confinement, while
      it stays approximately constant for slit-like confinement. These properties ought
      to reverberate in different kinetic properties of linear DNA depending on
      confinement and could be detectable experimentally or exploitable in nano
      technological applications. 

PMID- 23860874
TI  - Impact of the topology of viral RNAs on their encapsulation by virus coat
      proteins.
AB  - Single-stranded RNAs of simple viruses seem to be topologically more compact than
      other types of single-stranded RNA. It has been suggested that this has an
      evolutionary purpose: more compact structures are more easily encapsulated in the
      limited space that the cavity of the virus capsid offers. We employ a simple
      Flory theory to calculate the optimal amount of polymers confined in a viral
      shell. We find that the free energy gain or more specifically the efficiency of
      RNA encapsidation increases substantially with topological compactness. We also
      find that the optimal length of RNA encapsidated in a capsid increases with the
      degree of branching of the genome even though this effect is very weak. Further,
      we show that if the structure of the branching of the polymer is allowed to
      anneal, the optimal loading increases substantially. 

PMID- 23860876
TI  - Complex dynamics of defective interfering baculoviruses during serial passage in
      insect cells.
AB  - Defective interfering (DI) viruses are thought to cause oscillations in virus
      levels, known as the 'Von Magnus effect'. Interference by DI viruses has been
      proposed to underlie these dynamics, although experimental tests of this idea
      have not been forthcoming. For the baculoviruses, insect viruses commonly used
      for the expression of heterologous proteins in insect cells, the molecular
      mechanisms underlying DI generation have been investigated. However, the dynamics
      of baculovirus populations harboring DIs have not been studied in detail. In
      order to address this issue, we used quantitative real-time PCR to determine the
      levels of helper and DI viruses during 50 serial passages of Autographa
      californica multiple nucleopolyhedrovirus (AcMNPV) in Sf21 cells. Unexpectedly,
      the helper and DI viruses changed levels largely in phase, and oscillations were
      highly irregular, suggesting the presence of chaos. We therefore developed a
      simple mathematical model of baculovirus-DI dynamics. This theoretical model
      reproduced patterns qualitatively similar to the experimental data. Although we
      cannot exclude that experimental variation (noise) plays an important role in
      generating the observed patterns, the presence of chaos in the model dynamics was
      confirmed with the computation of the maximal Lyapunov exponent, and a Ruelle
      Takens-Newhouse route to chaos was identified at decreasing production of DI
      viruses, using mutation as a control parameter. Our results contribute to a
      better understanding of the dynamics of DI baculoviruses, and suggest that
      changes in virus levels over passages may exhibit chaos. 

PMID- 23860875
TI  - Design rules for nanomedical engineering: from physical virology to the
      applications of virus-based materials in medicine.
AB  - Physical virology seeks to define the principles of physics underlying viral
      infections, traditionally focusing on the fundamental processes governing virus
      assembly, maturation, and disassembly. A detailed understanding of virus
      structure and assembly has facilitated the development and analysis of virus
      based materials for medical applications. In this Physical Virology review
      article, we discuss the recent developments in nanomedicine that help us to
      understand how physical properties affect the in vivo fate and clinical impact of
      (virus-based) nanoparticles. We summarize and discuss the design rules that need
      to be considered for the successful development and translation of virus-based
      nanomaterials from bench to bedside. 

PMID- 23860877
TI  - Anti-TCR gamma antibody in celiac disease: the value of count on formalin-fixed
      paraffin-embedded biopsies.
AB  - Small bowel intraepithelial lymphocytosis (IL) may depend from different causes,
      including celiac disease (CD). Demonstration of increased number of duodenal T
      cell receptor gamma-delta (TCRgammadelta) positive intraepithelial lymphocytes
      (IELs) has been used to support CD diagnosis on frozen material. This work
      evaluates a new commercially available anti-TCRgamma antibody on formalin-fixed
      paraffin embedded (FFPE) small bowel biopsies. Anti-CD3 and anti-TCR CgammaM1
      (clone gamma3.20) from Thermo Scientific were applied by immunohistochemistry on
      59 FFPE biopsies from 18 cases of CD with mild/severe atrophy, 19 cases of IL in
      CD patients on gluten-free diet (IL-GFD), 14 cases of IL (6/14 with positive CD
      related serology), and 8 controls (CTR) with mild duodenitis and negative CD
      serology and genotyping. IELs/100 epithelial cells were counted in at least six
      high power fields. CD3+ and TCRgamma+ IELs were significantly higher in CD, IL
      GFD, and IL compared with CTR, but in contrast to CD3+ IELs, TCRgamma+ IELs were
      significantly increased in CD and IL-GFD compared with IL. Furthermore, TCRgamma+
      IELs discriminated between IL with negative and positive CD-related serology (p =
      0.02). TCRgamma+ IELs can be identified on FFPE samples and their evaluation adds
      useful information for the work-up of small bowel biopsies in CD diagnosis. In
      fact, TCRgamma staining coupled with CD3, may represent an additional tool to
      recognize cases of latent/potential CD when serology and clinical data are not
      conclusive or when the histological diagnosis remains equivocal. 

PMID- 23860878
TI  - Surgeon elective abdominal aortic aneurysm repair volume and outcomes of ruptured
      abdominal aortic aneurysm repair: a 12-year nationwide study.
AB  - BACKGROUND: The purpose of the present study was to examine the effects of
      surgeon elective abdominal aortic aneurysm repair volume on outcomes after
      ruptured abdominal aortic aneurysm (rAAA) repair. METHODS: A nationwide claims
      database was used to identify patients who underwent rAAA repair from 1998 to
      2009. Surgeon elective open abdominal aortic aneurysm repair (EAR) volume was
      classified as low, medium, or high. Associations between surgeon EAR volume and
      in-hospital mortality, overall survival, and complications after open rAAA repair
      (RAR) were compared with multivariate analysis. Associations between surgeon
      elective endovascular abdominal aortic aneurysm repair (EER) volume and outcomes
      after endovascular rAAA repair (RER) were also analyzed. RESULTS: A total of 537
      patients who underwent rAAA repair were identified, including 498 who underwent
      RAR and 39 who underwent RER. In-hospital mortality rates after RAR were 49, 38,
      and 24 % in the low, medium, and high EAR volume groups, respectively (p <
      0.001). Patients in the low surgeon EAR volume group had higher in-hospital
      mortality than those in the high surgeon EAR volume group [odds ratio 3.39, 95 %
      confidence interval (CI) 1.52, 7.59; p = 0.003]. Patients in the low surgeon EAR
      volume group also had higher long-term mortality (hazard ratio 1.86, 95 % CI
      1.21, 2.85; p = 0.005). There were no significant differences in complication
      rates among the surgeon EAR volume groups or in-hospital mortality after RER
      among the surgeon EER volume groups. CONCLUSIONS: Surgeon EAR volume is
      associated with in-hospital mortality and long-term survival after RAR.

PMID- 23860879
TI  - Stapleless laparoscopic splenectomy with individual vessel dissection in patients
      with splenomegaly.
AB  - BACKGROUND: Mechanical stapling devices have been established as a mainstay in
      laparoscopic splenectomy (LS), but limited data are available regarding
      stapleless LS for splenomegaly with individual vessel dissection (IVD). This
      study aimed to investigate the feasibility of stapleless LS for splenomegaly and
      its potential advantage over staple-based LS. METHODS: A total of 51 patients
      with splenomegaly underwent stapleless LS and were subsequently reviewed. The
      data collected include the patients' demographics, operative outcomes, and the
      rates of conversion to open surgery, complications, and mortality. Multiple
      linear and logistic regression analyses were used to assess the impact of the
      primary diagnosis, body mass index (BMI), and massive splenomegaly on the
      perioperative conversion rate. RESULTS: There were no deaths. The mean for
      various parameters are as follows: spleen length 21.6 cm; spleen weight 1,184 g,
      operating time 148 min, hospital stay 5.2 days, estimated blood loss 245 ml. The
      total conversion rate was 9.8 % (including one reoperation for bleeding). The
      presence of a BMI >30 % and hematologic malignancy-cofactors of portal
      hypertension (PH)-and a spleen weight >1,000 g were independent predictors of
      conversion to open surgery. CONCLUSIONS: Stapleless LS for splenomegaly is
      feasible and safe in selected patients. It has advantages over traditional
      procedures using staples, at least in patients with benign splenomegaly. Patients
      with hematologic malignancy, BMI >30 %, coexistence of PH, and spleen weight
      >1,000 g are susceptible to bleeding during dissection of the splenic hilum, with
      use of IVD being relatively limited.

PMID- 23860882
TI  - Funding opportunities for clinical investigators in the early stages of career
      development in cardiovascular research.
AB  - Contemporary cardiovascular research offers junior investigators the opportunity
      to explore the gamut of biomedical questions. Despite the recent reduction in the
      availability of funding mechanisms that have historically served as the primary
      pathways for investigators in the early stages of career development, there
      remain numerous traditional and non-traditional funding opportunities. This
      article highlights these opportunities in order to assist early career
      investigators in the development of a personalized research trajectory, which
      optimizes the potential for career success. 

PMID- 23860881
TI  - Autoantibodies to phosphorylcholine and cardiovascular outcomes in patients with
      acute coronary syndromes in the ATLAS ACS-TIMI 46 trial.
AB  - Atherogenesis is a complex inflammatory process stemming from the accumulation
      and oxidation of low density lipoproteins (LDL). IgM autoantibodies against
      phosphorylcholine (anti-PC) bind to the PC epitope on oxidized LDL (OxLDL),
      inhibiting the uptake of oxLDL by macrophages in atherosclerotic lesions. Anti-PC
      autoantibodies have been reported to be protective against atherothrombosis. We
      investigated the relationship of anti-PC concentrations with cardiovascular
      outcomes in patients with acute coronary syndromes (ACS). We measured anti-PC
      levels within 7 days of an ACS in 3,356 patients enrolled in the ATLAS ACS-TIMI
      46 trial, a randomized dose ranging study of rivaroxaban versus placebo. The
      primary endpoint was death, myocardial infarction (MI), stroke, or severe
      recurrent ischemia (SRI) requiring revascularization during 6 months. The median
      baseline anti-PC concentration was 40.9 U/mL (25th, 75th percentiles: 25.4,
      67.4). There was no significant association between anti-PC levels and the
      primary endpoint (Q1: 6.8 %, Q2: 4.2 %, Q3: 7.8 %, Q4: 5.4 %, p-trend = 0.87),
      all-cause mortality (Q1: 1.4 %, Q2: 0.7 %, Q3: 2.4 %, Q4: 0.9 %, p-trend = 0.
      96), or any of the other individual endpoint components (MI: p-trend = 0.87,
      Stroke: p-trend = 0.43, SRI: p-trend = 0.66). Using the previously reported anti
      PC cutpoint of 17 U/mL did not reveal a significant relationship between anti-PC
      concentrations and cardiovascular outcomes (<17 U/mL: 8.1 % vs. >=17 U/mL: 5.8 %;
      p = 0.11). Similarly, evaluation of anti-PC as a continuous variable did not
      reveal a significant association (p = 0.30). In this study of patients early
      after ACS undergoing intensive secondary preventive therapy, IgM anti-PC titers
      did not exhibit a significant relationship with cardiovascular outcomes. 

PMID- 23860883
TI  - Use of ticagrelor in patients with ST-elevation myocardial infarction undergoing
      thrombolysis.

PMID- 23860880
TI  - The pharmacology of novel oral anticoagulants.
AB  - Anticoagulation for the prevention of stroke is an important aspect of the
      management of atrial fibrillation. Novel anticoagulants including oral factor Xa
      inhibitors rivaroxaban and apixaban and the direct thrombin inhibitor dabigatran
      have emerged as important therapeutic treatment options for prevention of stroke
      in non-valvular atrial fibrillation. These agents offer practical advantages over
      traditional vitamin K antagonists, however an understanding of their individual
      pharmacokinetic and other agent-specific differences is essential for identifying
      appropriate candidates for therapy, and for selecting the appropriate agent that
      will be effective and safe. Here, we review the pharmacokinetic process of oral
      medication use, summarize the newer anticoagulants, their pharmacology,
      individual pharmacokinetic features, and explore possible explanations for the
      differences in bleeding outcomes observed in the clinical trials. 

PMID- 23860884
TI  - Islamic medical ethics a thousand years ago.

PMID- 23860885
TI  - Tuberculosis infection during Hajj pilgrimage. The risk to pilgrims and their
      communities.
AB  - Millions of Muslims travel to Makkah every year to perform Hajj. Many pilgrims
      come from countries with a high incidence of tuberculosis (TB). Over-crowding,
      physical exhaustion, heat, and co-morbid conditions of mostly middle-aged and
      elderly pilgrims make them susceptible to infection, or reactivation of latent
      TB. Evidence from previous reports indicated a significant risk of acquiring
      infection during Hajj. Pilgrims infected in Makkah may spread the infection to
      contacts in their countries. Spread of multi-drug resistant TB is a real concern.
      Control efforts are required to reduce the risk of infection and transmission.
      Screening of pilgrims from high burden countries before travel with chest x-ray
      will help to detect and treat active TB, and prevent infection of others. Low
      incidence countries may consider carrying out tuberculin skin test or Quanti
      FERON TB assay for pilgrims before and after Hajj, to identify and treat recent
      converters. National and international coordinated efforts are essential for
      successful implementation of control measures to prevent the spread of the
      disease. 

PMID- 23860886
TI  - Breast cancer awareness and breast self-examination in Northern Saudi Arabia. A
      preliminary survey.
AB  - OBJECTIVE: To elicit knowledge of breast cancer, perception of occurrence, and
      behavior in relation to breast self-examination (BSE). METHODS: A cross-sectional
      survey was carried out at the Department of Pathology, Medical College,
      University of Hail, Hail, Kingdom of Saudi Arabia for local occupants from Hail
      city and its rural neighborhood between September 2010 and February 2012. A
      personal interview-administered descriptive questionnaire and both descriptive
      and inferential statistics were used. RESULTS: A total of 1000 participants
      agreed to be involved, out of which 87.7% were females, 7.2% were males and 5.1%
      had undisclosed gender. The age range for participants was 12-66 years. Out of
      all participants, 44% did not know that breast cancer is an abnormal growth and
      78% failed to recognise its multi-factorial nature, with Increased age being the
      least recognised single risk factor 4.8%. Scores showed that 61.5% had a low
      level of breast cancer related knowledge. Out of the participants who knew of
      someone who had breast cancer 73%, 50.1% said the disease was discovered at a
      Late stage mainly by Chance. Data for BSE indicated that 50.1% of female
      participants >16 years old did not practice BSE, and Fear was the main declared
      perceived reason. CONCLUSION: This study demonstrates a low level of fundamental
      knowledge of breast cancer and fear to practice BSE.

PMID- 23860887
TI  - The role of interleukin-6 promoter polymorphism -174G/C in Saudi women with
      hypertensive disorders of pregnancy.
AB  - OBJECTIVE: To study the relationship between -174 GC interleukin-6 single
      nucleotide polymorphism and hypertensive disorders of pregnancy (HDP) in Saudi
      women. METHODS: In this case-control study, 109 HDP patients and 100 women with
      normal pregnancy as a control group were studied. The HDP study group constituted
      of 60 women with gestational hypertension (GH) and 49 women with preeclampsia
      (PE). All women were randomly selected from the antenatal clinic and the prenatal
      and postnatal wards at the Antenatal Clinic and the Obstetric Ward of King Khalid
      University Hospital, Riyadh, Kingdom of Saudi Arabia from April 2010 to December
      2011. The -174 GC of IL-6 SNP was determined using real time polymerase chain
      reaction, allele discrimination technique. RESULTS: Distribution of -174 GC of IL
      6 genotype in HDP patients was GG (58.5%), GC (31.1%), and CC (10.4%), while in
      the control group was GG (67%), GC (30.9%), and CC (2.1%). The CC homozygosity
      was significantly associated with HDP (odds ratio [OR] = 5.76; 95% confidence
      interval [CI] 1.23-27.06, p=0.03). This association only manifested with GH (OR =
      7.65; 95% CI = 1.54-38.03, p=0.01). However, no significant association was found
      with PE (OR = 3.48; 95% CI = 0.55-21.99, p=0.19). CONCLUSION: The results
      indicate a positive association between -174 GC of IL-6 genotype and the risk of
      HDP. Genotypes CC and GC are associated with increased risk of GH but not with
      PE, suggesting that they are of differing genetic predisposition/pathophysiology.

PMID- 23860888
TI  - Percutaneous endoscopic gastrostomy tube placement in children with
      neurodevelopmental disabilities. Parents' perspectives.
AB  - OBJECTIVE: To study the attitudes of parents toward percutaneous endoscopic
      gastrostomy (PEG) tube placement and identify contributing factors to their
      negative attitudes. METHODS: Thirty consecutive parents were included
      retrospectively through a single endoscopy unit at the King Abdulaziz University
      Hospital, Jeddah, Kingdom of Saudi Arabia from January to July 2012. A structured
      25-item questionnaire was designed to examine their demographics, attitudes, and
      experience with the PEG procedure. RESULTS: Patients' ages were 3-19 years (mean:
      10.2), mostly with severe cerebral palsy (77%). Their PEG tubes were inserted 2
      144 months (mean: 39) prior to the encounter. Only 43% of the parents felt
      informed and most (73%) had negative attitudes toward the procedure, which was
      associated with significant delays (p=0.016). After the procedure, most parents
      (67%) reported a better-than-expected experience, which was associated with their
      information levels (p=0.03). Most parents (80%) regretted not having the PEG tube
      placed earlier. This depended on their information level, as those who were not
      informed were more likely to have strong regrets when compared to those informed
      (82% versus 42%, p=0.008). CONCLUSION: Most parents are not well-informed
      regarding the PEG procedure, which affects their expectations and experiences.
      Most parents found the experience better than what they expected and regretted
      not having carried it out earlier.

PMID- 23860889
TI  - Melatonin attenuates hippocampal neuron apoptosis and oxidative stress during
      chronic intermittent hypoxia via up-regulating B-cell lymphoma-2 and down
      regulating B-cell lymphoma-2-associated X protein.
AB  - OBJECTIVE: To investigate the neuroprotective effect of melatonin against chronic
      intermittent hypoxia (CIH), the major pathophysiologic features of obstructive
      sleep apnea syndrome. METHODS: This study was conducted between January 2011 and
      September 2012 in Tongji Hospital, Huazhong University of Science and Technology,
      Wuhan, China. Thirty 8-week Wistar rats were randomly divided into 3 groups (10
      each): a control group, a vehicle-treated CIH group; and a melatonin-treated (10
      mg/kg) CIH group. Rats were exposed to either intermittent hypoxia (IH) (oxygen
      concentration changing periodically from 21.78+/-0.65 to 6.57+/-0.57%), or air
      air cycling at a rate of 30 cycles/hour, 8 hour/day for 4 weeks. RESULTS: The CIH
      exposure led to a significant decrease in superoxide dismutase (SOD) activity and
      anti-apoptotic protein B-cell lymphoma-2 (BCL-2) expression in the hippocampus of
      CIH group rats compared with that of the control group and melatonin-treated CIH
      group. In contrast, hippocampal neuronal apoptosis increased significantly in
      parallel to an augment in 3,4-methylenedioxyamphetamine (MDA) content and pro
      apoptotic protein Bcl-2-associated X protein (BAX) expression in CIH group than
      the other 2 groups. Melatonin administration abrogated the increase in MDA
      activity, as well as BAX expression, and restored SOD activity and BCL-2
      expression to nearly their normal levels. CONCLUSION: These results indicate
      melatonin can inhibit hippocampal neuron apoptosis following CIH by scavenging
      reactive oxygen species, up-regulating anti-apoptotic protein BCL-2 and down
      regulating pro-apoptotic protein BAX, and thus, alleviate CIH-induced oxidative
      stress injury and produce neuroprotection effects.

PMID- 23860890
TI  - Blood loss closely correlates with body mass index in total hip arthroplasty
      performed through direct lateral approach.
AB  - OBJECTIVE: To investigate total blood loss (TBL), intraoperative blood loss
      (IBL), post-operative drainage (POD), and other related variables in total hip
      arthroplasty (THA) performed through direct lateral approach. METHODS: This study
      was completed in Shanghai Sixth People's Hospital, Shanghai, China, between
      January and December 2010. We analyzed 113 patients treated by THA through direct
      lateral approach. Recordable blood loss (RBL) was measured and TBL was calculated
      according to the Gross formula. Ordinal logistic regression analysis was used for
      TBL, IBL, and POD, with gender, age, body mass index (BMI), disease duration, and
      operative time as independent variables. RESULTS: The average operative time was
      51.5 +/- 10.4 (range: 35-70) minutes, with an average RBL of 454 +/- 144 (range:
      150-180) ml. Average TBL was significantly higher (975 +/- 355, range: 430-2020
      ml; p<0.001). In the analysis of variables, BMI closely correlated with TBL, IBL,
      and POD, with odds ratios of 4.80 (95% CI: 2.63-8.78 [TBL]), 5.39 (95% CI: 2.84
      10.25 [IBL]), and 4.37 (95% CI: 2.43-7.89 [POD]). Moreover, TBL (54.172), IBL
      (55.198), and POD (39.139) correlated with trend test BMI. CONCLUSION: The TBL,
      IBL, and POD closely correlate with BMI in patients undergoing THA through direct
      lateral approach.

PMID- 23860891
TI  - Investigation of intestinal parasites in dialysis patients.
AB  - OBJECTIVE: To search for the opportunistic and other pathogenic intestinal
      parasites in dialysis patients, and to compare the methods used for diagnosis.
      METHODS: This is a randomized study, which recruited participants from the
      dialysis patients. The study was carried out in the Department of Microbiology,
      Research Hospital, School of Medicine in Kocaeli University, Kocaeli, Turkey
      between June 2012 and March 2013. One hundred and forty-two patients were
      diagnosed with an end-stage renal failure, which underwent dialysis, and 150
      healthy volunteers were enrolled in the study. Native-lugol, formol ethyl acetate
      sedimentation method, trichrome, modified trichrome, acid fast, and Calcofluor
      staining methods were applied to the stool samples. For the diagnosis of
      Cryptosporidium spp., Giardia intestinalis (G. intestinalis), and Entamoeba
      histolytica (E. histolytica), commercially available ELISA kits were used, which
      detect antigen in the stool. RESULTS: Parasites were found in 62 of the dialysis
      patients (43.7%) and 19 of the control group (12.7%). The most encountered
      parasitic agents in the dialysis patients were Blastocystis spp. (23.9%), G.
      intestinalis (8.5%), E. histolytica (2.1%), Microsporidia spp. (2.1%), and
      Cryptosporidium spp. (2.1%). The parasite detection rate of the formol ethyl
      acetate sedimentation method was found to be higher than native-lugol (p<0.05).
      CONCLUSION: To protect the dialysis patients with diarrhea from parasitic
      infections, it is important to carry out interval stool examinations with
      trichrome, modified trichrome, acid fast, and Calcofluor staining methods, and
      the ELISA method, which detects antigen in the stool.

PMID- 23860892
TI  - Prognostic value of late gadolinium enhancement in dilated cardiomyopathy
      patients. A meta-analysis.
AB  - OBJECTIVE: To evaluate the prognostic value of late gadolinium enhancement (LGE)
      in dilated cardiomyopathy (DCM) patients. METHODS: We searched PubMed, MEDLINE,
      the Cochrane library and EMBASE databases from September to December 2012 in the
      Renmin Hospital of Wuhan University, Wuhan, China for studies of LGE in DCM
      patients. We extracted the clinical outcomes (all-cause mortality, cardiovascular
      mortality, sudden cardiac death [SCD], aborted SCD, heart failure
      hospitalization) after carefully reviewed. A meta-analysis was performed to
      calculate pooled odds ratios (OR) with 95% confidence intervals (CIs) for
      prognostic outcomes in LGE positive versus LGE negative patients with DCM.
      RESULTS: Five studies for 545 DCM patients were contained in this meta-analysis.
      The results showed LGE positive patients was significantly associated with higher
      cardiovascular mortality (pooled OR: 2.67; 95% CI: 1.12-6.35; p=0.03), aborted
      SCD (pooled OR: 5.26; 95% CI: 1.57-17.55; p=0.007), and heart failure
      hospitalization (pooled OR: 3.91; 95% CI: 1.99-7.69; p<0.001). CONCLUSION: Late
      gadolinium enhancement during cardiac MRI is significantly associated with
      cardiovascular mortality, aborted SCD and heart failure hospitalization in DCM
      patients. The LGE can be a potential stratification tool to predict the risk of
      cardiac events among patients with DCM.

PMID- 23860893
TI  - The role of Acacia Arabica extract as an antidiabetic, antihyperlipidemic, and
      antioxidant in streptozotocin-induced diabetic rats.
AB  - OBJECTIVE: To investigate the role of Acacia Arabica extract as a hypoglycemic,
      antihyperlipidemic, and antioxidant agent in streptozotocin-induced diabetic
      rats. METHODS: This is an animal experimental study conducted in King Fahd
      Research Center, King Abdulaziz University (KAU), Jeddah, Kingdom of Saudi Arabia
      from December 2012 to January 2013. Thirty-six female albino rats were divided
      into 2 equal groups; the first served as control, and the second was the
      streptozotocin-induced diabetic group. Each group was subdivided into 3
      subgroups, each of 6 rats; the first was left untreated, the second and the third
      were treated with Acacia Arabica extract orally for 21 days (100 mg/kg for the
      second group and 200 mg/kg for the third group). On the twenty-first day, blood
      samples were withdrawn through the retro-orbital plexus of overnight fasted rats
      under light ether anesthesia for determination of serum glucose, insulin, total
      cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL
      C), low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and
      coenzyme Q10 (Co-Q10). RESULTS: A significant decrease in levels of serum
      glucose, insulin resistance, TC, TG, LDL-C, MDA and a significant increase in HDL
      C and Co-Q10 was observed in the treated diabetic groups when compared to the
      untreated diabetic group. The changes were dose dependent. CONCLUSION: The
      results found in this study indicate that Acacia Arabica extract has
      hypoglycemic, hypolipidemic, and antioxidant properties, therefore, it can be
      investigated for its efficacy in the treatment of diabetes in humans.

PMID- 23860894
TI  - Effects of green tea and vitamin E in the testicular tissue of streptozotocin
      induced diabetic rats.
AB  - OBJECTIVE: To investigate the possible therapeutic or protective effects of green
      tea in diabetic rat's testicular tissue, either as a single agent, or together
      with vitamin E. METHODS: The present study was carried out at the Faculty of
      Medicine, Gazi University, Ankara, Turkey from May to August 2011 for 10 weeks.
      Forty-eight adult male Wistar albino rats, weighting 250-300 g, were divided into
      8 groups: control; nondiabetic vitamin E (0.4 mg/kg/NG); nondiabetic green tea
      (300 mg/kg/NG); nondiabetic vitamin E plus green tea administered groups;
      diabetic group (60 mg/kg/IV streptozotocin); diabetic vitamin E; diabetic green
      tea; and diabetic vitamin E plus green tea administered groups. Proliferative and
      apoptotic indexes were determined using anti-PCNA antibody immunohistochemistry
      and TUNEL assays respectively. Tubule degeneration was evaluated using the
      Johnson's score and also seminiferous tubules diameters, epithelial thickness
      were measured. RESULTS: Histopathological examination in diabetic group revealed
      degenerative changes in the seminiferous tubules together with a statistically
      significant decrease in PCNA positive cells, in epithelial thickness, diameter of
      the tubules and in Johnson's score, while exhibited an increase in the number of
      apoptotic cells. When all these findings are considered together, the most
      successful protective effects in diabetes were obtained in the combined
      antioxidant group. CONCLUSION: Combined therapy of vitamin E and green tea in
      diabetes was more effective than monotherapy. Therefore, these antioxidants may
      be use as a supporting therapy for reproductive dysfunction.

PMID- 23860895
TI  - Dental caries. A meta analysis on a Saudi population.
AB  - OBJECTIVE: To determine the prevalence of caries in the primary and permanent
      teeth in a Saudi population. METHODS: This study was conducted at the College of
      Dentistry, University of Dammam, Dammam, Kingdom of Saudi Arabia. In June 2010, a
      literature search was started and found all studies conducted in Saudi Arabia on
      dental caries from 1999 to 2008. Sixty articles were found on PubMed, which had
      been published during the considered time period. Sixteen studies were passed
      through inclusion criteria and included in analysis. A 2 to 12-year-old Saudi
      population was included to determine the prevalence of caries in primary teeth,
      and for permanent teeth, the age range was 6-18 years. RESULTS: The prevalence of
      caries in primary and permanent teeth were analyzed separately. Forest plot and
      Chi-square test revealed considerable heterogeneity. A random effect model was
      used to find caries prevalence in primary and permanent teeth. The mean decayed,
      missing, and filled teeth (dmft) was 5.38 (95% CI: 4.314 - 6.436), and in the
      permanent teeth the DMFT was 3.34 (95% CI: 1.97 - 4.75). Publication bias
      diagnostics suggested possible overestimation of caries prevalence in permanent
      teeth but not in primary teeth. CONCLUSION: The results in this study present a
      high decayed, missing, and filled teeth score in the adult and young population
      of Saudi Arabia, however, more published data is required as the results obtained
      from this meta analysis may not give a true picture, and reality may be worse.

PMID- 23860896
TI  - Giant pedunculated esophageal liposarcoma associated with Hurthle cell thyroid
      neoplasia.
AB  - Giant pedunculated liposarcoma of the esophagus is considered a rare entity. They
      impose difficulties in management, especially the surgical approach. We report a
      case of giant pedunculated liposarcoma of the esophagus in a 62-year-old male who
      underwent cervical excision of this large tumor, and made a full recovery.
      Hurthle cell thyroid cancer was found during the work-up, which was managed
      accordingly. 

PMID- 23860897
TI  - Placenta percreta and uterine rupture at 16 weeks.
AB  - Placenta percreta is a complication of pregnancy with significant morbidity and
      mortality rates. Spontaneous uterine rupture in early pregnancy due to placenta
      percreta is rare. We report a case of this life-threatening complication
      occurring at the sixteenth week of gestation. The patient presented with signs of
      shock, acute abdomen, and evidence of hemoperitoneum. The pregnancy was viable
      with a normal ultrasound appearance that created some confusion and there was a
      dilemma in the diagnosis of this case. Various obstetric and surgical causes were
      taken into consideration. The patient was taken to the operating room immediately
      for exploratory laparotomy. She was found to have fundal uterine rupture, which
      was managed by uterine repair. This patient had prior cesarean section and
      dilatation and curettage; factors well known to predispose for placenta percreta.
      Here, we emphasize the importance of a fast decision and surgical intervention to
      save a patient's life in cases of uterine rupture. 

PMID- 23860898
TI  - Effects of a 12-week aerobic training on glycemic control in type 2 diabetes
      mellitus male patients.

PMID- 23860899
TI  - Is focal segmental glomerulosclerosis common among the elderly? Geriatric biopsy
      results.

PMID- 23860900
TI  - Catalytic and regulatory roles of species involved in metal-nucleotide
      equilibriums in human pyridoxal kinase.
AB  - Pyridoxal 5'-phosphate is the active form of vitamin B6 and its deficiency is
      directly related with several human disorders, which make human pyridoxal kinase
      (hPLK) an important pharmacologic target. In spite of this, a carefully kinetic
      characterization of hPLK including the main species that regulates the enzymatic
      activity is at date missing. Here we analyse the catalytic and regulatory
      mechanisms of hPLK as a function of a precise determination of the species
      involved in metal-nucleotide equilibriums and describe new regulatory mechanisms
      for this enzyme. hPLK activity is supported by several metals, being Zn(2+) the
      most effective, although the magnitude of the effect observed is highly dependent
      on the relative concentrations of metal and nucleotide used. The true substrate
      for the reaction catalyzed by hPLK is the metal nucleotide complex, while ATP(4-)
      and HATP(3-) did not affect the activity. The enzyme presents substrate
      inhibition by both pyridoxal (PL) and ZnATP(2-), although the latter behaves as a
      weakly inhibitor. Our study also established, for the first time, a dual role for
      free Zn(2+); as an activator at low concentrations (19 MUM optimal concentration)
      and as a potent inhibitor with a IC50 of 37 MUM. These results highlighted the
      importance of an accurate estimation of the actual concentration of the species
      involved in metal-nucleotide equilibriums in order to obtain reliable values for
      the kinetic parameters, and for determine the true regulators of the PLK
      activity. They also help to explain the dissimilar kinetic parameters reported in
      the literature for this enzyme.

PMID- 23860902
TI  - Influence of bone insertion level of the implant on the fracture strength of
      different connection designs: an in vitro study.
AB  - OBJECTIVE: The aim of the present in vitro study was to assess resistance to
      static fatigue of implants with different connections at various insertion
      levels. MATERIALS AND METHODS: Sixty implants and abutments were used with the
      smallest diameter of each model. Four groups (n = 15) were created on the basis
      of the implant design and connection: cylindrical external hexagon O3.30 mm
      (group 1), cylindrical internal hexagon O3.30 mm (group 2), conical internal
      hexagon O3.50 mm (group 3), and conical Morse taper O3.50 mm (group 4). Three
      insertion levels in resin were tested, 0 mm at the platform level (l1), 3 mm
      (l2), and 5 mm (l3) above the platform of the resin. All groups were subjected to
      quasi-static loading at 30 degrees  to the implant axis in a universal machine.
      RESULTS: The mean fracture strengths for group 1 were 1,991 N (l1), 1,020 N (l2),
      and 767 N (l3); for group 2: 2,119 N (l1), 1,034 N (l2), and 903 N (l3); for
      group 3: 2,373 N (l1), 1,407 N (l2), and 929 N (l3); and for group 4: 1,710 N
      (l1), 1,680 N (l2), and 1,182 N (l3). CONCLUSIONS: Resistance to loading
      decreases significantly with the loss of insertion, and the connection design
      between the implants and abutments can change the performance and resistance of
      the system. CLINICAL RELEVANCE: When implants are used in areas where there is a
      possibility of bone loss, the selection of a connection type is an important
      consideration for the longevity of the system.

PMID- 23860901
TI  - Natural compounds containing mouthrinses in the management of dental plaque and
      gingivitis: a systematic review.
AB  - OBJECTIVES: To evaluate the effectiveness of natural compounds containing
      mouthrinse (NCCM) as an adjunct to unsupervised oral hygiene in the management of
      dental plaque and gingivitis. MATERIALS AND METHODS: An electronic search for
      clinical studies of NCCMs was conducted in Medline-PubMed, the Cochrane Central
      Register of Controlled Trials and EMBASE for a period spanning from the earliest
      available date in each database up to February 2013. Plaque index, gingival
      index, and gingival bleeding index were selected as primary outcomes. The
      methodological quality of the studies was assessed according to the "Levels of
      Evidence" outlined by the Center of Evidence-Based Medicine, and to the Jadad
      scale. RESULTS: The screen yielded 2,236 titles and abstracts that met the
      inclusion criteria. These identified 11 clinical trials testing 13 different
      NCCMs, and were used for data extraction. Heterogeneity and the limited number of
      studies on any individual NCCM precluded a formal meta-analysis. Of the 13 NCCMs
      tested, eight demonstrated positive results, and few reported any adverse effects
      or events. CONCLUSIONS: Evidence proving the effectiveness of NCCM as an adjunct
      to unsupervised oral hygiene for plaque and gingivitis control is still
      insufficient. However, some natural products (compounds) may have oral health
      benefits, so further high-quality study is warranted. CLINICAL RELEVANCE: This
      review provides an overview of the strength of clinical evidence regarding the
      effectiveness of natural compounds containing mouthrinses in promoting gingival
      health.

PMID- 23860903
TI  - Primary migration of a mini-implant under a functional orthodontic loading.
AB  - OBJECTIVES: The objective of this study was to examine whether cortical bone
      thickness and bone mineral density (BMD) can explain the primary migration of a
      mini-implant under a functional orthodontic tangential loading at the early stage
      following implantation. MATERIALS AND METHODS: Mini-implants were installed in
      human mandibular sections. A constant tangential load (2 N) was applied to the
      mini-implant under hydration. Creep, which is a time-dependent viscoelastic
      displacement in the bone surrounding the mini-implant, was assessed as the change
      in displacement during 2 h of loading. The total migration was measured as a
      maximum displacement that combined an initial elastic displacement and creep.
      After removal of the mini-implant, all specimens were scanned together by cone
      beam computed tomography. Cortical bone thickness and BMD were measured for the
      bone voxels surrounding the implant site. RESULTS: BMD had significant
      correlations with the displacement parameters (p < 0.019), but the cortical bone
      thickness did not (p > 0.272). Permanent bone deformation adjacent to the implant
      was observed to be resulting from substantial creep development under the
      orthodontic functional loading level. CONCLUSIONS: BMD controls the primary
      migration of the mini-implant system in mandibular bone. Viscoelastic creep can
      develop at a small constant functional loading level, leading to migration of the
      mini-implant. CLINICAL RELEVANCE: The current results indicated that mini-implant
      migration can develop under the small level of functional orthodontic load used
      in clinic. If the active bone remodeling around the mini-implant accelerates the
      migration, the risk of causing damage in vital organs next to the mini-implant
      increases.

PMID- 23860904
TI  - Emerging applications of conjugated polymers in molecular imaging.
AB  - In recent years, conjugated polymers have attracted considerable attention from
      the imaging community as a new class of contrast agent due to their intriguing
      structural, chemical, and optical properties. Their size and emission wavelength
      tunability, brightness, photostability, and low toxicity have been demonstrated
      in a wide range of in vitro sensing and cellular imaging applications, and have
      just begun to show impact in in vivo settings. In this Perspective, we summarize
      recent advances in engineering conjugated polymers as imaging contrast agents,
      their emerging applications in molecular imaging (referred to as in vivo uses in
      this paper), as well as our perspectives on future research. 

PMID- 23860905
TI  - Cationic gold(I) heteroleptic complexes bearing a pyrazole-derived N-heterocyclic
      carbene: syntheses, characterizations, and cytotoxic activities.
AB  - A series of cationic gold(I) heteroleptic complexes bearing the pyrazole-derived
      N-heterocyclic carbene (NHC) FPyr (1,2,3,4,6,7,8,9-octahydropyridazino[1,2
      a]indazolin-11-ylidene), and either a 1,3-disubstituted benzimidazole-derived NHC
      of the type RR'-bimy (3: R = R' = CHPh2; 4: R = CHPh2, R' = (i)Pr; 5: R = R' =
      CH2Ph; 6: R = R' = (i)Bu; 7: R = R' = n-Pr; 8: R = R' = Et; 9: R = R' = 2
      propenyl) or a non-NHC co-ligand L (10: L = PPh3; 11: L = P(OPh)3; 12: L = DMAP)
      (DMAP = 4-dimethylaminopyridine) have been synthesized from [AuCl(FPyr)] (1).
      Complexes 3-12 have been characterized using multinuclei NMR spectroscopies, ESI
      mass spectrometry, and elemental analysis. X-ray diffraction analyses have been
      performed on complexes 5, 6, and 9-11. To the best of our knowledge, 11
      represents the first gold-NHC complex to bear the P(OPh)3 ligand. The cytotoxic
      activities of complexes 3-12 have been studied in vitro with the NCI-H1666 non
      small cell lung cancer cell line.

PMID- 23860906
TI  - Non-stationary (13)C-metabolic flux ratio analysis.
AB  - (13)C-metabolic flux analysis ((13)C-MFA) has become a key method for metabolic
      engineering and systems biology. In the most common methodology, fluxes are
      calculated by global isotopomer balancing and iterative fitting to stationary
      (13)C-labeling data. This approach requires a closed carbon balance, long-lasting
      metabolic steady state, and the detection of (13)C-patterns in a large number of
      metabolites. These restrictions mostly reduced the application of (13)C-MFA to
      the central carbon metabolism of well-studied model organisms grown in minimal
      media with a single carbon source. Here we introduce non-stationary (13)C
      metabolic flux ratio analysis as a novel method for (13)C-MFA to allow estimating
      local, relative fluxes from ultra-short (13)C-labeling experiments and without
      the need for global isotopomer balancing. The approach relies on the acquisition
      of non-stationary (13)C-labeling data exclusively for metabolites in the
      proximity of a node of converging fluxes and a local parameter estimation with a
      system of ordinary differential equations. We developed a generalized workflow
      that takes into account reaction types and the availability of mass spectrometric
      data on molecular ions or fragments for data processing, modeling, parameter and
      error estimation. We demonstrated the approach by analyzing three key nodes of
      converging fluxes in central metabolism of Bacillus subtilis. We obtained flux
      estimates that are in agreement with published results obtained from steady state
      experiments, but reduced the duration of the necessary (13)C-labeling experiment
      to less than a minute. These results show that our strategy enables to formally
      estimate relative pathway fluxes on extremely short time scale, neglecting
      cellular carbon balancing. Hence this approach paves the road to targeted (13)C
      MFA in dynamic systems with multiple carbon sources and towards rich media.

PMID- 23860908
TI  - Synthesis of binuclear phenoxyimino organoaluminum complexes and their use as the
      catalyst precursors for efficient ring-opening polymerisation of epsilon
      caprolactone.
AB  - A series of novel binuclear phenoxyimino organoaluminum complexes of the type
      [(RN=CH)C6H3OAlMe2]2 [R = C6H5 (2a), 2,6-(i)Pr2C6H3 (2b), 2,6-Ph2C6H3 (2c),
      adamantyl (2d), (t)Bu (2e)] have been prepared in high yields, and these
      complexes were identified by (1)H, (13)C NMR and elemental analysis. Structural
      analysis for 2a-e revealed that these complexes have a distorted tetrahedral
      geometry around Al and both the Al-O and the Al-N bond distances were
      considerably influenced by substituents in the imino groups. The complexes were
      tested as catalyst precursors for ring-opening polymerisation (ROP) of epsilon
      caprolactone (CL) in the presence of BnOH, and their catalytic activities were
      strongly affected by the catalyst structures and polymerisation conditions. An
      efficient living ROP has been achieved using the 2b/BnOH system.

PMID- 23860907
TI  - Spelling well despite developmental language disorder: what makes it possible?
AB  - The goal of the study was to investigate the overlap between developmental
      language disorder (DLD) and developmental dyslexia, identified through spelling
      difficulties (SD), in Russian-speaking children. In particular, we studied the
      role of phoneme awareness (PA), rapid automatized naming (RAN), pseudoword
      repetition (PWR), morphological (MA), and orthographic awareness (OA) in
      differentiating between children with DLD who have SD from children with DLD who
      are average spellers by comparing the two groups to each other, to typically
      developing children as well as children with SD but without spoken language
      deficits. One hundred forty-nine children, aged 10.40 to 14.00 years,
      participated in the study. The results indicated that the SD, DLD, and DLD/SD
      groups did not differ from each other on PA and RAN Letters and underperformed in
      comparison to the control groups. However, whereas the children with written
      language deficits (SD and DLD/SD groups) underperformed on RAN Objects and
      Digits, PWR, OA, and MA, the children with DLD and no SD performed similarly to
      the children from the control groups on these measures. In contrast, the two
      groups with spoken language deficits (DLD and DLD/SD) underperformed on RAN
      Colors in comparison to the control groups and the group of children with SD
      only. The results support the notion that those children with DLD who have
      unimpaired PWR and RAN skills are able to overcome their weaknesses in spoken
      language and PA and acquire basic literacy on a par with their age peers with
      typical language. We also argue that our findings support a multifactorial model
      of DLD. 

PMID- 23860909
TI  - Alpha-fetoprotein-producing clear cell carcinoma of the gallbladder with
      neuroendocrine differentiation.
AB  - An uncommon case of alpha-fetoprotein (AFP) producing clear cell carcinoma of the
      gallbladder with neuroendocrine differentiation in a 78-year-old Japanese woman,
      who complained of epigastralgia, is reported. Macroscopically, the nodular
      infiltrative type of tumor, measuring approximately 4.5 * 3.5 cm in size, was
      located in the fundus of the gallbladder. Histologically, the tumor was composed
      of clear cell carcinoma with AFP production, non-clear cell adenocarcinoma with
      neuroendocrine differentiation, and poorly or undifferentiated carcinoma with
      extensive ulceration. Carcinoma in situ was found in the surrounding gallbladder
      epithelium. Her postoperative laboratory tests showed a decrease in AFP levels to
      normal. The clinical and pathologic significance of AFP production or
      neuroendocrine differentiation in the gallbladder carcinomas have thus far
      remained completely obscure. However, we should recognize the entity of this
      tumor because the accurate diagnosis of primary clear cell carcinoma of the
      gallbladder may have important therapeutic implications. 

PMID- 23860910
TI  - Expression of the Ly-6 family proteins Lynx1 and Ly6H in the rat brain is
      compartmentalized, cell-type specific, and developmentally regulated.
AB  - The Ly-6 superfamily of proteins, which affects diverse processes in the immune
      system, has attracted renewed attention due to the ability of some Ly-6 proteins
      to bind to and modulate the function of neuronal nicotinic acetylcholine
      receptors (nAChRs). However, there is a scarcity of knowledge regarding the
      distribution and developmental regulation of these proteins in the brain. We use
      protein cross-linking and synaptosomal fractions to demonstrate that the Ly-6
      proteins Lynx1 and Ly6H are membrane-bound proteins in the brain, which are
      present on the cell surface and localize to synaptic compartments. We further
      estimate the amount of Lynx1 in the rat cortex using known amounts of a
      heterologously expressed soluble Lynx1 variant (ws-Lynx1) to be approximately 8.6
      ng/MUg total protein, which is in line with the concentrations of ws-Lynx1
      required to affect nAChR function. In addition, we demonstrate that Lynx1 and
      Ly6H are expressed in cultured neurons, but not cultured micro- or astroglial
      cultures. In addition, Lynx1, but not Ly6H was detected in the CSF. Finally, we
      show that the Ly-6 proteins Lynx1, Lynx2, Ly6H, and PSCA, display distinct
      expression patterns during postnatal development in the rat frontal cortex and
      hippocampus at the mRNA and protein level, and that this is paralleled to some
      degree by the expression of the nAChR subunits alpha2, alpha4, alpha7 and beta2.
      Our results demonstrate a developmental pattern, localization, and concentration
      of Ly-6 proteins in the brain, which support a role for these proteins in the
      modulation of signaling at synaptic membranes. 

PMID- 23860911
TI  - Combining sperm plug genotyping and coat color chimerism predicts germline
      transmission.
AB  - There has been a significant increase in the use of C57BL/6N-derived ES cells for
      the production of gene knockout mice. However, the potential for germline
      transmission (GLT) from chimeras on this genetic background has been observed to
      be highly variable. Using coat color as an indicator of somatic chimerism to
      infer the extent of chimeric contribution to the germ cell population, even
      highly agouti C57BL/6N-derived chimeras can fail to achieve GLT. We investigated
      the extent to which quantitative PCR genotyping for a marker gene expressed in
      gene targeted ES cells can be performed on DNA extracted from sperm present in
      copulatory plugs to determine the contribution of ES cells to the germ cells. We
      found that an objective assessment of sperm DNA from copulatory plugs combined
      with a subjective assessment of coat color chimerism can be used to accurately
      inform the selection of chimeras for breeding that are likely to achieve GLT.
      These results indicate that, compared to random selection of chimeras, including
      an analysis of copulatory plugs to set chimeras for breeding can help to reduce
      costs, minimize time, and facilitate research for projects requiring the
      production, selection, breeding, and testing of chimeras to generate gene
      targeted mice. 

PMID- 23860913
TI  - Conformational properties of interacting neurofilaments: Monte Carlo simulations
      of cylindrically grafted apposing neurofilament brushes.
AB  - Neurofilaments are essential cytoskeletal filaments that impart mechanical
      stability to axons. They are mostly assembled from three neurofilament proteins
      that form the core of the filament and its sidearms. Adjacent neurofilaments
      interact with each other through their apposing sidearms and attain unique
      conformations depending on the ionic condition, phosphorylation state, and
      interfilament separations. To understand the conformational properties of
      apposing sidearms under various conditions and gain insight into interfilament
      interactions, we performed Monte Carlo simulations of neurofilament pairs. We
      employed a sequence-based coarse-grained model of apposing NF sidearms that are
      end-tethered to cylindrical geometries according to the stoichiometry of the
      three neurofilament subunits. Monte Carlo simulations were conducted under
      different conditions such as phosphorylation state, ionic condition, and
      interfilament separations. Under salt-free conditions, apposing sidearms are
      found to adopt mutually excluding stretched but bent away conformations that are
      reminiscent of a repulsive type of interaction. Under physiological conditions,
      apposing sidearms are found to be in a coiled conformation, suggesting a short
      range steric repulsive type of interaction. Increased sidearm mutual
      interpenetration and a simultaneous decrease in the individual brush heights were
      observed as the interfilament separation was reduced from 60 to 40 nm. The
      observed conformations suggest entropic interaction as a likely mechanism for
      sidearm-mediated interfilament interactions under physiological conditions. 

PMID- 23860914
TI  - Structure-driven homology pairing of chromatin fibers: the role of electrostatics
      and protein-induced bridging.
AB  - Chromatin domains formed in vivo are characterized by different types of 3D
      organization of interconnected nucleosomes and architectural proteins. Here, we
      quantitatively test a hypothesis that the similarities in the structure of
      chromatin fibers (which we call "structural homology") can affect their mutual
      electrostatic and protein-mediated bridging interactions. For example, highly
      repetitive DNA sequences in heterochromatic regions can position nucleosomes so
      that preferred inter-nucleosomal distances are preserved on the surfaces of
      neighboring fibers. On the contrary, the segments of chromatin fiber formed on
      unrelated DNA sequences have different geometrical parameters and lack structural
      complementarity pivotal for stable association and cohesion. Furthermore,
      specific functional elements such as insulator regions, transcription start and
      termination sites, and replication origins are characterized by strong nucleosome
      ordering that might induce structure-driven iterations of chromatin fibers. We
      propose that shape-specific protein-bridging interactions facilitate long-range
      pairing of chromatin fragments, while for closely-juxtaposed fibers electrostatic
      forces can in addition yield fine-tuned structure-specific recognition and
      pairing. These pairing effects can account for some features observed for mitotic
      and inter-phase chromatins. 

PMID- 23860915
TI  - Development of a DNA sensor using a molecular logic gate.
AB  - This communication reports the increase in fluorescence resonance energy transfer
      (FRET) efficiency between two laser dyes in the presence of deoxyribonucleic acid
      (DNA). Two types of molecular logic gates have been designed where DNA acts as
      input signal and fluorescence intensity of different bands are taken as output
      signal. Use of these logic gates as a DNA sensor has been demonstrated. 

PMID- 23860916
TI  - The influence of millimeter waves on the physical properties of large and giant
      unilamellar vesicles.
AB  - Exposure of cell membranes to an electromagnetic field (EMF) in the millimeter
      wave band (30-300 GHz) can produce a variety of responses. Further, many of the
      vibrational modes in complex biomolecules fall in the 1-100 GHz range. In
      addition to fundamental scientific interest, this may have applications in the
      development of diagnostic and therapeutic medical applications. In the present
      work, lipid vesicles of different size were used to study the effects of exposure
      to radiation at 52-72 GHz, with incident power densities (IPD) of 0.0035-0.010
      mW/cm(2), on the chemical-physical properties of cell membranes. Large
      unilamellar vesicles (LUVs) were used to study the effect of the radiation on the
      physical stability of vesicles by dynamic light scattering. An inhibition of the
      aging processes (Ostwald ripening), which usually occur in these vesicles because
      of their thermodynamic instability, resulted. Giant unilamellar vesicles (GUVs)
      were used to study the effect of the radiation on membrane water permeability
      under osmotic stress by phase contrast microscopy. In this case, a decrease in
      the water membrane permeability of the irradiated samples was observed. We
      advance the hypothesis that both the above effects may be explained in terms of a
      change of the polarization states of water induced by the radiation, which causes
      a partial dehydration of the membrane and consequently a greater packing density
      (increased membrane rigidity).

PMID- 23860917
TI  - The effect of body temperature on the dynamic respiratory system compliance
      breathing frequency relationship in the rat.
AB  - The mechanical inhomogeneity of the respiratory system is frequently investigated
      by measuring the frequency dependence of dynamic compliance, but no data are
      currently available describing the effects of body temperature variations. The
      aim of the present report was to study those effects in vivo. Peak airway
      pressure was measured during positive pressure ventilation in eight anesthetized
      rats while breathing frequency (but not tidal volume) was altered. Dynamic
      compliance was calculated as the tidal volume/peak airway pressure, and
      measurements were taken in basal conditions (mean rectal temperature 37.3 
      degrees C) as well as after total body warming (mean rectal temperature 39.7 
      degrees C). Due to parenchymal mechanical inhomogeneity and stress relaxation
      linked effects, the normal rat respiratory system exhibited frequency dependence
      of dynamic lung compliance. Even moderate body temperature increments
      significantly reduced the decrements in dynamic compliance linked to breathing
      rate increments. The results were analyzed using Student's and Wilcoxon's tests,
      which yielded the same results (p < 0.05). Body temperature variations are known
      to influence respiratory mechanics. The frequency dependence of dynamic
      compliance was found, in the experiments described, to be temperature-dependent
      as temperature variations affected parenchymal mechanical inhomogeneity and
      stress relaxation. These results suggest that body temperature variations should
      be taken into consideration when the dynamic compliance-breathing frequency
      relationship is being examined during clinical assessment of inhomogeneity of
      lung parenchyma in patients.

PMID- 23860918
TI  - Pyrazolo[3,4-d]pyrimidines as inhibitor of anti-coagulation and inflammation
      activities of phospholipase A 2 : insight from molecular docking studies.
AB  - Phospholipase A2 (PLA2), isolated from Daboia russelli pulchella (Russell's
      viper), is enzymatically active as well as induces several pharmacological
      disorders including neurotoxicity, myotoxicity, cardiotoxicity, anti-coagulant,
      hemolytic, and platelet effects. Indomethacin reduces the effects of anti
      coagulant and pro-inflammatory actions of PLA2. Pyrazolo[3,4-d]pyrimidines
      constitute a class of naturally occurring fused uracils that posses diverse
      biological activities. The in-silico docking studies of nine pyrazolo[3,4
      d]pyrimidine molecules have been carried out with the X-ray crystal structure of
      Russell's viper PLA2 (PDB ID: 3H1X) to predict the binding affinity, molecular
      recognition, and to explicate the binding modes, using AUTODOCK and GLIDE
      (Standard precision and Extra precision) modules, respectively. Docking results
      through each method make obvious that pyrazolo[3,4-d]pyrimidine molecules with
      trimethylene linker can bind with both anti-coagulation and enzymatic regions of
      PLA2. 

PMID- 23860919
TI  - A modified active Brownian dynamics model using asymmetric energy conversion and
      its application to the molecular motor system.
AB  - We consider a modified energy depot model in the overdamped limit using an
      asymmetric energy conversion rate, which consists of linear and quadratic terms
      in an active particle's velocity. In order to analyze our model, we adopt a
      system of molecular motors on a microtubule and employ a flashing ratchet
      potential synchronized to a stochastic energy supply. By performing an active
      Brownian dynamics simulation, we investigate effects of the active force, thermal
      noise, external load, and energy-supply rate. Our model yields the stepping and
      stalling behaviors of the conventional molecular motor. The active force is found
      to facilitate the forwardly processive stepping motion, while the thermal noise
      reduces the stall force by enhancing relatively the backward stepping motion
      under external loads. The stall force in our model decreases as the energy-supply
      rate is decreased. Hence, assuming the Michaelis-Menten relation between the
      energy-supply rate and the an ATP concentration, our model describes ATP
      dependent stall force in contrast to kinesin-1. 

PMID- 23860920
TI  - Maximum sustainable yield and species extinction in a prey-predator system: some
      new results.
AB  - Though the maximum sustainable yield (MSY) approach has been legally adopted for
      the management of world fisheries, it does not provide any guarantee against from
      species extinction in multispecies communities. In the present article, we
      describe the appropriateness of the MSY policy in a Holling-Tanner prey-predator
      system with different types of functional responses. It is observed that for both
      type I and type II functional responses, harvesting of either prey or predator
      species at the MSY level is a sustainable fishing policy. In the case of combined
      harvesting, both the species coexist at the maximum sustainable total yield
      (MSTY) level if the biotic potential of the prey species is greater than a
      threshold value. Further, increase of the biotic potential beyond the threshold
      value affects the persistence of the system. 

PMID- 23860921
TI  - Mathematical modeling of cascading migration in a tri-trophic food-chain system.
AB  - Diel vertical migration is a behavioral antipredator defense that is shaped by a
      trade-off between higher predation risk in surface waters and reduced growth in
      deeper waters. The strength of migration of zooplankton increases with a rise in
      the abundance of predators and their exudates (kairomone). Recent studies span
      multiple trophic levels, which lead to the concept of coupled vertical migration.
      The migrations that occur at one trophic level can affect the vertical migration
      of the next lower trophic level, and so on, throughout the food chain. This is
      called cascading migration. In this paper, we introduce cascading migration in a
      well-known model (Hastings and Powell, Ecology 73:896-903, 1991). We represent
      the dynamics of the system as proposed by Hastings and Powell as a phytoplankton
      zooplankton-fish (prey-middle predator-top predator) model where fish affect the
      migrations of zooplankton, which in turn affect the migrations of motile
      phytoplankton. The system under cascading migration enhances system stability and
      population coexistence. It is also observed that for a higher rate of cascading
      migration, the system shows chaotic behavior. We conclude that the observations
      of Hastings and Powell remain true if the cascading migration rate is high
      enough. 

PMID- 23860922
TI  - Modeling epidemic spread with awareness and heterogeneous transmission rates in
      networks.
AB  - During an epidemic outbreak in a human population, susceptibility to infection
      can be reduced by raising awareness of the disease. In this paper, we investigate
      the effects of three forms of awareness (i.e., contact, local, and global) on the
      spread of a disease in a random network. Connectivity-correlated transmission
      rates are assumed. By using the mean-field theory and numerical simulation, we
      show that both local and contact awareness can raise the epidemic thresholds
      while the global awareness cannot, which mirrors the recent results of Wu et al.
      The obtained results point out that individual behaviors in the presence of an
      infectious disease has a great influence on the epidemic dynamics. Our method
      enriches mean-field analysis in epidemic models. 

PMID- 23860923
TI  - Spatial pattern characterization of linear polarization-sensitive backscattering
      Mueller matrix elements of human serum albumin sphere suspension.
AB  - Human serum albumin (HSA) nanometer or micron particles represent promising drug
      carrier systems. The azimuthal and radial variations of a linear polarization
      sensitive backscattering Mueller matrix were experimentally studied in two cases:
      the scattering particle was smaller or larger in size to the probing wavelength
      of 780 nm. The results show that the twofold and fourfold structures are
      characteristic of small particle size suspension, whereas the eightfold structure
      is characteristic of large particle size suspension. Moreover, for both particle
      size suspensions, the element patterns have strong radial dependence when the
      suspension concentration and the incident power of laser change. In addition, for
      both particle size suspensions, the rotational symmetry of each element is lost
      in the case of oblique incidence but the multifold structure is maintained. Some
      suggestions for applications of Mueller matrix imaging in biomedical optics are
      provided.

PMID- 23860924
TI  - Computer model of unstirred layer and intracellular pH changes. Determinants of
      unstirred layer pH.
AB  - Transmembrane acid-base fluxes affect the intracellular pH and unstirred layer pH
      around a superfused biological preparation. In this paper the factors influencing
      the unstirred layer pH and its gradient are studied. An analytical expression of
      the unstirred layer pH gradient in steady state is derived as a function of
      simultaneous transmembrane fluxes of (weak) acids and bases with the dehydration
      reaction of carbonic acid in equilibrium. Also a multicompartment computer model
      is described consisting of the extracellular bulk compartment, different
      unstirred layer compartments and the intracellular compartment. With this model
      also transient changes and the influence of carbonic anhydrase (CA) can be
      studied. The analytical expression and simulations with the multicompartment
      model demonstrate that in steady state the unstirred layer pH and its gradient
      are influenced by the size and type of transmembrane flux of acids and bases,
      their dissociation constant and diffusion coefficient, the concentration,
      diffusion coefficient and type of mobile buffers and the activity and location of
      CA. Similar principles contribute to the amplitude of the unstirred layer pH
      transients. According to these models an immobile buffer does not influence the
      steady-state pH, but reduces the amplitude of pH transients especially when these
      are fast. The unstirred layer pH provides useful information about transmembrane
      acid-base fluxes. This paper gives more insight how the unstirred layer pH and
      its transients can be interpreted. Methodological issues are discussed. 

PMID- 23860925
TI  - Proteins searching for their target on DNA by one-dimensional diffusion:
      overcoming the "speed-stability" paradox.
AB  - The sequence dependence of DNA-protein interactions that allows proteins to find
      the correct reaction site also slows down the 1D diffusion of the protein along
      the DNA molecule, leading to the so-called "speed-stability paradox," wherein
      fast diffusion along the DNA molecule is seemingly incompatible with stable
      targeting of the reaction site. Here, we develop diffusion-reaction models that
      use discrete and continuous Gaussian random 1D diffusion landscapes with or
      without a high-energy cut-off, and two-state models with a transition to and from
      a "searching" mode in which the protein diffuses rapidly without recognizing the
      target. We show the conditions under which such considerations lead to a
      predicted speed-up of the targeting process, and under which the presence of a
      "searching" mode in a two-state model is nearly equivalent to the existence of a
      high-energy cut-off in a one-state model. We also determine the conditions under
      which the search is either diffusion-limited or reaction-limited, and develop
      quantitative expressions for the rate of successful targeting as a function of
      the site-specific reaction rate, the roughness of the DNA-protein interaction
      potential, and the presence of a "searching" mode. In general, we find that a
      rough landscape is compatible with a fast search if the highest energy barriers
      can be avoided by "hopping" or by the protein transitioning to a lower-energy
      "searching" mode. We validate these predictions with the results of Brownian
      dynamics, kinetic Metropolis, and kinetic Monte Carlo simulations of the
      diffusion and targeting process, and apply these concepts to the case of T7 RNA
      polymerase searching for its target site on T7 DNA. 

PMID- 23860926
TI  - Five or more years of adjuvant endocrine therapy in breast cancer: a meta
      analysis of published randomised trials.
AB  - Five years of adjuvant hormonal therapy is the standard of care in early breast
      cancer (BC) expressing oestrogen receptors (ER+). Prolonged duration of adjuvant
      endocrine therapy is implemented to prevent recurrence and death; in particular,
      its carryover effect may prevent very late events. This meta-analysis compares
      the efficacy of 5 years of hormonal therapy alone with that of additional years
      of hormonal therapy, in patients with early BC. Randomised trials comparing 5
      years versus more than 5 years of hormonal therapy in BC were identified by
      electronic searches of PubMed, EMBASE, ISI Web of Science and the Cochrane
      Central Register of Controlled Trials. Meta-analysis was performed using the
      fixed- or random-effects models. The primary endpoints were overall survival
      (OS), BC-specific survival (BCSS) and relapse-free survival (RFS) reported as
      odds ratios (ORs) and 95 % confidence interval (CI). Eight trials, including
      29,138 patients, were identified. Overall, in ER+ BCs, extended endocrine therapy
      beyond 5 years of tamoxifen significantly improved OS (OR, 0.89; 95 % CI 0.80
      0.99; P = 0.03), BCSS (OR, 0.78; 95 % CI 0.69-0.9; P = 0.0003) and RFS (OR 0.72;
      95 % CI 0.56-0.92; P = 0.01) compared with 5 years of hormonal therapy alone.
      Loco-regional and distant relapses were reduced by 36 and 13 %, respectively.
      Compared with 5 years of tamoxifen, additional adjuvant endocrine therapy reduced
      risk of death and relapse of ER+ BC by ~10 and 30 %, respectively. This strategy
      should be considered in patients free of disease after 5 years of hormonal
      therapy. 

PMID- 23860927
TI  - Lack of circadian variation and reduction of heart rate variability in women with
      breast cancer undergoing lumpectomy: a descriptive study.
AB  - Changes in the autonomic nervous system with increased sympathetic tone may be a
      cause of postoperative short-, and long-term cardiovascular complications. Heart
      rate variability (HRV) is assessed by Holter monitoring as a measure of autonomic
      tone and has not been investigated in patients with breast cancer undergoing
      surgery. We aimed to investigate evening- and night-time HRV after lumpectomy.
      Twelve patients were included in this descriptive study. HRV was measured the
      night before surgery (PREOP), the night after surgery (PO1) and 14 days after
      surgery (PO14) from 1900 to 0700 h. For calculation of HRV, time domain
      parameters (SDNN-standard deviation of all normal-to-normal (NN) intervals around
      the mean NN for the period of measurement, pNN50-percentage of beats where the
      change from one beat to the next is more than 50 ms, rMSSD-root mean square of
      successive differences) were used. We analyzed the variation of the overall time
      period and the circadian variation between evening and night (sympathetic vs.
      parasympathetic tonus). Mean heart rate increased from PREOP to PO1 (p < 0.001)
      and also increased between PREOP and PO14 (p < 0.05). SDNN (p < 0.001) and PNN50
      (p < 0.001) decreased from PREOP to PO1. There was also a significant decrease
      between PREOP and PO14 for both parameters (p < 0.005 and p = 0.05 respectively).
      SDNN increased from PO1 to PO14 (p < 0.005). rMSSD decreased from PREOP to PO1 (p
      < 0.001). A circadian variation was found in the mean heart rate for all three
      monitoring periods (p < 0.005). Circadian variation was also present on PREOP for
      pNN50 (p <= 0.05) and rMSSD (p < 0.05). This variation was missing for both PO1
      and PO14. Patients had a shift of autonomic tone with reduced parasympathetic
      activity and lack of circadian variation 14 days after lumpectomy. 

PMID- 23860928
TI  - Increased expression of mitotic arrest deficient-like 1 (MAD1L1) is associated
      with poor prognosis and insensitive to Taxol treatment in breast cancer.
AB  - Aneuploidy is a characteristic of human cancers, and recent studies have
      suggested that defects of mitotic checkpoints play a role in carcinogenesis.
      Mitotic Arrest Deficient-Like 1 (MAD1L1), whose altered expression is associated
      with chromosomal instability, is a checkpoint gene. We examined MAD1L1 protein
      expression from 461 breast cancer tissues and patients' normal breast tissues by
      tissue microarray to study the correlation between the MAD1L1 expression and the
      clinicopathological features. MAD1L1 protein expression was significantly
      increased in the nuclei of cancer cells (28.4 %) compared with that in normal
      mammary cells (2.2 %), and was correlated with Her-2 status, cancer subtypes, p53
      status, and age. High level of MAD1L1 expression in nuclei was associated with
      worse OS (p = 0.018). Furthermore, patients with high level of MAD1L1 expression
      (in nuclei) and undergone Taxol chemotherapy treatment have shorter overall
      survival than ones without Taxol treatment in this study (p = 0.026). In
      conclusion, our data demonstrated a significant correlation between nuclear
      expression of MAD1L1 protein and adverse prognosis in breast cancer. MAD1L1 might
      be used as a prognostic biomarker for breast cancer and expression of MAD1L1 in
      nuclei is also a predict biomarker of contraindication to pacilitaxel treatment
      in breast cancer. 

PMID- 23860929
TI  - Molecular imaging with a fluorescent antibody targeting carbonic anhydrase IX can
      successfully detect hypoxic ductal carcinoma in situ of the breast.
AB  - Ductal carcinoma in situ (DCIS) of the breast is difficult to remove completely
      during surgery as it is not palpable and can therefore require re-excision. Real
      time visualization of DCIS using near-infrared fluorescent probes could help the
      surgeon during surgery as well as the pathologist post-operatively to distinguish
      the tumor from healthy tissue. As hypoxia-induced necrosis is a common phenomenon
      in DCIS, we investigated the molecular imaging of DCIS using a fluorescent
      antibody targeting a hypoxia marker, carbonic anhydrase IX (CAIX), in a
      preclinical mouse model. A monoclonal antibody against human CAIX was
      fluorescently labeled with the near-infrared dye IRDye800CW and characterized in
      vitro. An in vivo study was performed in SCID/Beige mice that were orthotopically
      transplanted with human breast cancer cells mimicking human DCIS (MCF10DCIS) and
      MCF10DCIS stably expressing CAIX. A clinically approved fluorescence imaging
      system was used to monitor probe uptake and to determine tumor-to-normal tissue
      ratios (TNR). Mean in vivo TNR of CAIX-transduced (CAIX+) tumors was 7.5 +/- 0.5.
      Mean in vivo TNR of DCIS tumors with hypoxic areas reached a plateau level at 48
      h after injection of 2.1 +/- 0.1 (mean +/- SEM) compared to 1.7 +/- 0.1 in DCIS
      without hypoxic areas. Mean intra-operative TNR of DCIS tumors with necrotic
      regions was higher than that of DCIS tumors without necrotic regions 96 h after
      injection-2.9 +/- 0.1 and 1.5 +/- 0.1, respectively-while the TNR of CAIX+ tumors
      was 11.2 +/- 1.0. Specific tumor uptake of MabCAIX-IRDye800CW was confirmed by a
      biodistribution assay, and immunofluorescence imaging on tumor sections showed
      specific uptake in hypoxic tumor regions, with higher contrast than conventional
      chromagen-based immunohistochemistry. Molecular fluorescence imaging with MabCAIX
      IRDye800CW can be successfully used to detect hypoxic DCIS before and during
      surgery to facilitate radical resection. Furthermore, it allows for sensitive
      CAIX-specific immunofluorescence microscopy of tumor sections, thereby
      introducing the concept of molecular fluorescence pathology. 

PMID- 23860930
TI  - The silicone ring tourniquet in orthopaedic operations of the extremities.
AB  - Tourniquets provide a bloodless field in limb operations and their introduction
      in orthopaedic operative technique has been considered as a landmark. A new
      tourniquet device, a silicone ring tourniquet (SRT) (HemaClear or S-MART, OHK
      Medical Devices, Haifa, Israel), was introduced into clinical practice a few
      years ago. A few clinical studies as well as comparative studies in volunteers
      have reported its use in a relatively small number of cases. The aim of this
      prospective study is to report the clinical use of this device in a large number
      of patients, including all possible applications of a tourniquet. The SRT was
      used in 536 cases including 337 male and 119 female patients with a mean age of
      43.7 years (range 6 to 87 years). The average tourniquet time was 58.5 minutes
      (range 6 to 180 minutes). It was applied in 362 (67.5%) elective and in 174
      (32.5%) trauma cases including fractures (n:109, 62.6%) and soft-tissue injuries
      (n:65, 37.4%). The most frequent application site was the femur (n:255, 47.6%),
      followed by the forearm (n:154, 28.7%), humerus (n:65, 12.1%), and calf (n:62,
      11.6%). Because the device is sterile it was possible to use it in operations in
      which the pneumatic tourniquet cannot be used, such as open reduction and
      internal fixation of humeral shaft and femoral supracondylar fractures. In 14
      patients (2.6%), the tourniquet failed intraoperatively, and the cause was an
      unexpected raised blood pressure. The SRT - with a pre-set pressure according to
      the size and the tension model - is easy to apply. It is sterile, and occupies a
      narrow area of the limb. Its application combines three functions at the same
      time: exsanguination, tourniquet, and stockinet application. Although it cannot
      entirely replace the classic pneumatic tourniquet, it is a safe and useful device
      in orthopaedic operations because of its advantages. 

PMID- 23860932
TI  - A new minimally invasive treatment option for stress urinary incontinence in
      women: TVT Abbrevo, a shorter sling with an inside-out transobturator approach.
AB  - The aim of this article is to present a new, modified shorter obturator sling
      with an inside-out transobturator trajectory for the treatment of female stress
      urinary incontinence (SUI). It is a method that proves efficient, is
      reproducible, and is associated with less postoperative pain when compared with
      the conventional method. The modified procedure involves the use of less tape and
      reduced dissection in the obturator space, while pursuing a more medial approach.
      Tape length was shortened, with placement of non-absorbable suture loops at
      either end to adjust the sling. At the mid-portion of the sling, a removable loop
      suture ensures equidistance. This is the only mini-sling that can be adjusted
      allowing one to modify terminal placement along an anterior/posterior axis. The
      incidence of immediate postoperative groin pain was reduced by 35% in the
      modified technique as compared with the original inside-out transobturator
      approach. There was also reduction of immediate pain severity by +/- 50%. In
      addition, the modified approach required less analgesics, less time in the
      operating room, and a shortened time until discharge home. 

PMID- 23860931
TI  - Vagus nerve stimulation for standardized monitoring: technical notes for
      conventional and endoscopic thyroidectomy.
AB  - Standardization of the intraoperative neuromonitoring (IONM) technique is an
      essential aspect of modern monitored thyroid surgery. The standardized technique
      involves vagal nerve stimulation. VN stimulation is useful for technical problem
      solving, detecting non-recurrent laryngeal nerve (non-RLN), recognizing any
      recurrent laryngeal nerve (RLN) lesions, and precisely predicting RLN
      postoperative function. Herein, we present technical notes for the VN
      identification to achieve the critical view of safety of the VN stimulation with
      or without dissection. 

PMID- 23860933
TI  - A newly developed oval-shaped port device (E*Z ACCESS Oval type) for use in
      reduced port surgery: initial clinical experiences with cholecystectomy.
AB  - We recently developed an oval-shaped E*Z Access device designed exclusively for
      use with the LAP PROTECTORTM Oval type device (Hakko Co. Ltd., Tokyo, Japan). The
      transverse abdominal opening diameter made by round-shaped (Alexis(r) Wound
      Retractor, Applied Medical, Rancho Santa Margarita, CA; and LAP PROTECTORTM Round
      type) and oval-shaped (LAP PROTECTORTM Oval type) wound retractors was measured
      and compared in 5 patients with cholecystolithiasis. Each device was placed
      through a single 25-mm longitudinal umbilical incision, and the length of trocar
      separation was compared. LESS cholecystectomy was then performed using the oval
      shaped E*Z ACCESS/LAP PROTECTORTM. The transverse abdominal opening diameter was
      maximized with the LAP PROTECTORTM Oval type device. The average distance between
      the working-ports for the glove method, round-shaped, and oval-shaped E*Z
      ACCESS/LAP PROTECTORTM devices in the 25-mm umbilical incisions were 20 +/- 0.8
      mm, 24 +/- 1.5 mm, and 35 +/- 0.8 mm, respectively. Wider trocar separation was
      achieved using the oval-shaped device, making the surgical procedures easier to
      perform. No perioperative port-related or surgical complications were observed.
      LESS cholecystectomy using the E*Z ACCESS Oval type device was found to be
      technically feasible. The Oval type device appears to allow for wider trocar
      separation, thereby reducing stress on the surgeon, ensuring patient safety, and
      providing cosmetic benefits. 

PMID- 23860934
TI  - Primary total hip arthroplasty with a tapered Trabecular MetalTM coated femoral
      component: experience with a minimum 24-month follow-up.
AB  - We prospectively reviewed the clinical and radiological outcome of the first 32
      patients (32 hips) undergoing primary total hip arthroplasty using a Trabecular
      MetalTM coated tapered femoral component. Seventeen males and 15 females were
      included. Average age was 71.6 years (range 61.5-85 years). Mean duration of
      follow-up was 34 months (range 24-48 months) Average preoperative Oxford, Harris,
      and WOMAC scores were 34, 51, and 44, respectively. Mean postoperative scores
      were 18, 82, and 11, respectively (P < 0.001 for all scores). All patients
      reported relief of preoperative pain. There were no revisions. These results
      suggest that the Trabecular MetalTM taper femoral component successfully relieves
      pain and leads to a significant functional improvement in patients with
      symptomatic hip arthritis in the early postoperative period. 

PMID- 23860935
TI  - Comparison between unidirectional barbed and polyglactin 910 suture in vaginal
      cuff closure in patients undergoing total laparoscopic hysterectomy.
AB  - The aim of the study was to compare the efficacy and safety of barbed
      unidirectional vs. polyglactin 910 suture in vaginal cuff closure on patients
      submitted to total laparoscopic hysterectomy. From November 2011 until March
      2012, a prolective, comparative, longitudinal, non-randomized study was performed
      on patients submitted to total laparoscopic hysterectomy (TLH). On entry,
      patients were assigned to two different groups, Group 1: Vaginal cuff closure
      with unidirectional #00 (n = 25) barbed suture, and Group 2: Vaginal cuff closure
      with polyglactin 910 #1 suture. The length of closure time and the frequency of
      dehiscence in vaginal vault were measured on the 14th postoperative day. We did
      not find significant differences between the groups on the general characteristic
      analysis. However, significant differences were found (P = .029) in the average
      vaginal cuff closure time (12.7 +/- 3.1 min. for barbed suture group vs. 20.4 +/-
      7.1 min. for polyglactin 910 group). No dehiscence case was found in any group.
      Based on the results of this study, we can conclude that unidirectional barbed
      suture reduces the surgical time for vaginal cuff closure during total
      laparoscopic hysterectomy and doesn't increase the vaginal cuff dehiscence risk. 

PMID- 23860936
TI  - Management of patient and staff radiation dose in interventional radiology:
      current concepts.
AB  - The increasing complexity and numbers of interventional fluoroscopy procedures
      have led to increasing patient doses of radiation and to increasing concern over
      staff doses. Hybrid rooms incorporate multiple imaging modalities and are used by
      multidisciplinary teams in interventional fluoroscopy suites and operating
      theaters. These rooms present additional radiation protection challenges. The new
      low annual exposure limit for the lens of the eye also requires specific measures
      to prevent cataracts in operators. The traditional attitude of radiation
      protection must be changed to one of proactive management of radiation dose and
      image quality. Incorporation of a comprehensive dose management program into the
      departmental quality assurance program is now essential. Physicians,
      radiographers, and medical physicists play an essential role in the safe use of
      fluoroscopy in medical practice. Efficient use of all imaging modalities (e.g.,
      fluoroscopy, digital subtraction angiography, cone-beam CT) requires knowledge of
      the effects of different equipment settings on patient and staff doses as well as
      the skill and competence to optimize these settings for each procedure and
      patient. Updates and recommendations on radiation protection and dose management
      programs, including aspects of education and training, are presented. 

PMID- 23860937
TI  - Ultrasound-assisted thrombolysis in submassive and massive pulmonary embolism:
      assessment of lung obstruction before and after catheter-directed therapy.
AB  - PURPOSE: New treatment guidelines support the use of catheter-directed therapy
      for both massive and submassive pulmonary embolism (PE). This study examines the
      safety and effectiveness of ultrasound-accelerated (UA) thrombolysis, for which
      prompt treatment is warranted to rapidly resolve thrombus and restore
      cardiopulmonary function. MATERIALS AND METHODS: We retrospectively reviewed ten
      consecutive, acute submassive/massive PE patients. All patients exhibited acute
      symptoms and computed tomography evidence of large thrombus burden and evidence
      of right-ventricular (RV) dysfunction and/or failure. Patients were followed-up
      with posttreatment echocardiography (n = 7) and CT (n = 9) to evaluate right
      heart dysfunction and thrombus burden, respectively. Thrombolytic treatment was
      performed in all patients using the EkoSonic Endovascular system. Clinical
      outcomes and complications, RV pressures, and thrombus removal were evaluated.
      Paired Wilcoxon signed-rank tests were performed to analyze the pretreatment and
      posttreatment measures; p < 0.05 was considered significant. RESULTS: Median
      thrombolytic dose was 18.0 mg tissue plasminogen activator infused over 20.8 h.
      There was a significant decrease in pretreatment and posttreatment RV pressures
      (52.0-30.0; p < 0.01); there was a significant decrease in pretreatment and
      posttreatment Mastora obstructive indices (74-43; p < 0.01). All patients
      improved clinically shortly after treatment onset. All ten patients survived to
      discharge with a median intensive care (ICU) stay of 4 days and 14 hospital days.
      CONCLUSION: UA thrombolysis is promising in massive and submassive PE treatment
      and shows safe results. Patients showed improved thrombus burden, and rapid
      improvement in right cardiac function, whereas minimizing bleeding risk and ICU
      time were minimized. This results of this study provide the foundation for future
      comparative studies in treatment of large PEs.

PMID- 23860938
TI  - Transjugular intrahepatic portosystemic shunt for the treatment of Budd-Chiari
      syndrome patients: results from a single center.
AB  - PURPOSE: To evaluate the outcome of transjugular intrahepatic portosystemic shunt
      (TIPS) in patients with Budd-Chiari syndrome (BCS). PATIENTS AND METHODS:
      Fourteen patients (11 female, mean age 45.8 years), with symptomatic BCS
      refractory to conventional therapy, were treated with TIPS placement in our
      department within a period of 9 years. Stent grafts were primarily used in 12
      patients. Mean follow-up time was 38.1 +/- 36.1 months (range 7-114). Model for
      end-stage liver disease (MELD) score, BCS Rotterdam index, and Child-Pugh score
      were calculated for all patients. In addition, the recently suggested BCS-TIPS
      prognostic index score (BSC-TIPS PI) was applied. RESULTS: BCS-TIPS PI score was
      <=7 in all patients. Most of our patients (12 of 14) had good or intermediate
      prognosis according to MELD, Rotterdam and Child-Pugh scores. Technical success
      was achieved in all 14 patients and was accompanied by complete resolution of the
      symptoms. In 3 patients, the procedure was complicated by hemoperitoneum, which
      was successfully treated in two patients with coils or stent-graft placement,
      whereas 1 patient was managed in the operating room. Thirteen patients are
      symptom and orthotopic liver transplantation-free. Primary patency was 92.8,
      84.7, and 58.7 % at 6, 12, and 24 months, respectively. Secondary patency was
      100, 100 and 84.6 % at 6, 12, and 24 months respectively. CONCLUSION: In
      symptomatic BCS patients with moderate prognosis according to MELD, Child-Pugh,
      and BCS Rotterdam scores, as well as BCS-TIPS PI score <=7, TIPS has high
      clinical success, low morbidity, and no mortality, and it offers durable mid-term
      resolution of the symptoms and OLT-free survival.

PMID- 23860939
TI  - The suitability of three Galia melon cultivars and different types of cuts for
      the fresh-cut industry.
AB  - BACKGROUND: Melons (Cucumis melo L.) are widely cultivated in Mediterranean
      countries. For fresh-cut melon elaboration, factors such as type of cultivar and
      cut have a significant impact on final product quality. The quality parameters
      from long, medium and short shelf-life Galia melon cultivars, cut into different
      shapes such as slices, trapezoids and cylinders and stored up to 10 days at 5 
      degrees C, were evaluated in order to learn the suitability of these cultivars
      and type of cut for minimal processing. RESULTS: In general, long-life melon
      cultivar had a low respiration rate and ethylene emissions, and high tissue
      firmness, but low levels of glucose, fructose, vitamin C and flavor rating by
      consumers. However, despite having higher metabolic activity and susceptibility
      to microbial spoilage, the short shelf-life cultivar melon had higher firmness
      retention. This cultivar was characterized by its richness in glucose, fructose
      and vitamin C, and its sensory quality (flavor) was highly valued. In general,
      the medium cultivar had an intermediate behavior between long and short cultivars
      but without their positive attributes. As a consequence of the most intense
      damage, the cylindrical shape had higher metabolic activity, susceptibility to
      microbial spoilage and reduced appearance. CONCLUSIONS: In the long and medium
      life cultivars studied, low flavor was the limiting factor to extend the shelf
      life of fresh-cut melon while for the short-life cultivar the limiting factor was
      its susceptibility to bacterial growth. Cut types such as cylinders should be
      avoided.

PMID- 23860940
TI  - A flexible Eu(III)-based metal-organic framework: turn-off luminescent sensor for
      the detection of Fe(III) and picric acid.
AB  - A metal-organic framework (MOF) {[Eu2(MFDA)2(HCOO)2(H2O)6].H2O}n (1) (H2MFDA =
      9,9-dimethylfluorene-2,7-dicarboxylic acid) has been solvothermally synthesized
      and structurally characterized. 1 possesses the three-dimensional pcu type rod
      packing structure with one-dimensional rhombic channels. The framework of 1 can
      reversibly shrink/swell along the c axis upon partial/full release of the water
      molecules. Correspondingly, the rhombic channels become narrow/large and 1
      transforms to narrow-pore 1a/large-pore 1b. 1, 1a and 1b have almost the same
      excitation and emission spectra with the strong characteristic red-light-emission
      of Eu(III). A high photoluminescence quantum yield of 77% and long luminescence
      lifetime of around 1.1 ms was observed for 1. The potential of 1b for Fe(3+) ions
      and PA sensing was studied in DMF through the luminescence quenching experiments,
      which show 1b is a potential turn-off luminescent sensory material for the
      selective detection of Fe(3+) ions and PA with detection limits of around 10(-7)
      M for both of them. The fluorescence quenching mechanism for Fe(3+) ions and PA
      was also investigated.

PMID- 23860941
TI  - Preparation of reusable bioreactors using reversible immobilization of enzyme on
      monolithic porous polymer support with attached gold nanoparticles.
AB  - Porcine lipase has been reversibly immobilized on a monolithic polymer support
      containing thiol functionalities prepared within confines of a fused silica
      capillary and functionalized with gold nanoparticles. Use of gold nanoparticles
      enabled rejuvenation of the activity of the deactivated reactor simply by
      stripping the inactive enzyme from the nanoparticles using 2-mercaptoethanol and
      subsequent immobilization of fresh lipase. This flow through enzymatic reactor
      was then used to catalyze the hydrolysis of glyceryl tributyrate (tributyrin).
      The highest activity was found within a temperature range of 37-40 degrees C. The
      reaction kinetics is characterized by Michaelis-Menten constant, Km  = 10.9
      mmol/L, and maximum reaction rate, Vmax  = 5.0 mmol/L min. The maximum reaction
      rate for the immobilized enzyme is 1,000 times faster compared to lipase in
      solution. The fast reaction rate enabled to achieve 86.7% conversion of
      tributyrin in mere 2.5 min and an almost complete conversion in 10 min. The
      reactor lost only less than 10% of its activity even after continuous pumping
      through it a solution of substrate equaling 1,760 reactor volumes. Finally,
      potential application of this enzymatic reactor was demonstrated with the
      transesterification of triacylglycerides from kitchen oil to fatty acid methyl
      esters thus demonstrating the ability of the reactor to produce biodiesel.

PMID- 23860942
TI  - Impact of menopausal status on the outcome of pelvic floor physiotherapy in women
      with urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to evaluate the
      effectiveness of pelvic floor muscle training in pre- and postmenopausal women
      using a quality-of-life questionnaire. METHODS: We retrospectively reviewed the
      medical records of 96 patients with urinary incontinence who participated in a
      pelvic floor muscle-training (PFMT) program at the Physiotherapy Department in a
      London University Hospital between January 2010 and August 2011. RESULTS: A
      period of supervised PFMT resulted in significant improvement in symptoms of
      stress urinary incontinence, urge urinary incontinence, urgency, frequency, and
      nocturia, irrespective of menopausal status. CONCLUSIONS: Pre- and postmenopausal
      women experience similar outcomes in relation to urinary symptoms following a
      short-term supervised PFMT.

PMID- 23860943
TI  - Terahertz spectroscopy for the assessment of burn injuries in vivo.
AB  - A diagnosis criterion is proposed for noninvasive grading of burn injuries using
      terahertz radiation. Experimental results are presented from in vivo terahertz
      time-domain spectroscopy of second- and third-degree wounds, which are obtained
      in a 72-hour animal study. During this period, the change in the spectroscopic
      response of the burned tissue is studied. It is shown that terahertz waves are
      sensitive not only to the postburn formation of interstitial edema, but also to
      the density of skin structures derived from image processing analysis of
      histological sections. Based on these preliminary results, it is suggested that
      the combination of these two effects, as probed by terahertz spectroscopy of the
      tissue, may ultimately be used to differentiate partial-thickness burns that will
      naturally heal from those that will require surgical intervention.

PMID- 23860944
TI  - HIV and neurocognitive dysfunction.
AB  - The spectrum of HIV-associated neurocognitive disorder (HAND) has been
      dramatically altered in the setting of widely available effective antiretroviral
      therapy (ART). Once culminating in dementia in many individuals infected with
      HIV, HAND now typically manifests as more subtle, though still morbid, forms of
      cognitive impairment in persons surviving long-term with treated HIV infection.
      Despite the substantial improvement in severity of this disorder, the fact that
      neurologic injury persists despite ART remains a challenge to the community of
      patients, providers and investigators aiming to optimize quality of life for
      those living with HIV. Cognitive dysfunction in treated HIV may reflect early
      irreversible CNS injury accrued before ART is typically initiated, ongoing low
      level CNS infection and progressive injury in the setting of ART, or
      comborbidities including effects of treatment which may confound the beneficial
      reduction in viral replication and immune activation effected by ART. 

PMID- 23860945
TI  - Singing can facilitate foreign language learning.
AB  - This study presents the first experimental evidence that singing can facilitate
      short-term paired-associate phrase learning in an unfamiliar language
      (Hungarian). Sixty adult participants were randomly assigned to one of three
      "listen-and-repeat" learning conditions: speaking, rhythmic speaking, or singing.
      Participants in the singing condition showed superior overall performance on a
      collection of Hungarian language tests after a 15-min learning period, as
      compared with participants in the speaking and rhythmic speaking conditions. This
      superior performance was statistically significant (p < .05) for the two tests
      that required participants to recall and produce spoken Hungarian phrases. The
      differences in performance were not explained by potentially influencing factors
      such as age, gender, mood, phonological working memory ability, or musical
      ability and training. These results suggest that a "listen-and-sing" learning
      method can facilitate verbatim memory for spoken foreign language phrases. 

PMID- 23860946
TI  - Isolation, sequence characterization, and tissue transcription profiles of two
      novel buffalo genes: INSIG1 and INSIG2.
AB  - Insulin-induced genes (INSIGs) are recently discovered genes that are involved in
      the metabolism of cholesterol and lipogenesis in animal tissues. In this study,
      two INSIG genes (INSIG1 and INSIG2) were isolated and characterized in 11
      buffalo. The full-length coding sequence (CDS) of the buffalo INSIG1 consists of
      831 bp which encodes a 276 amino acid protein with molecular mass 29.55 kD. And
      the INSIG2 CDS is 678 bp in length which encodes a 225 amino acid protein with
      molecular mass 24.87 kD. No polymorphisms were found in the CDSs of the buffalo
      INSIGs, but seven and two nucleotide differences were found in the CDSs between
      buffalo and other bovine species. Phylogenetic analyses based on the INSIG amino
      acid sequences showed that buffalo was grouped with other members in the Bovidae
      family. Four types of putative modification sites were detected in buffalo INSIG
      proteins. And two predicted microRNA target sites were found respectively in the
      CDSs of buffalo INSIG1 and INSIG2. The tissue expression analyses by quantitative
      PCR (qPCR) revealed that the buffalo INSIG1 was expressed in ten tissues tested.
      Among these tissues, the liver and mammary gland showed high expression levels.
      And the INSIG2 was only expressed in the brain, mammary glands, pituitary,
      abomasum, heart, and liver. Among these tissues, the mammary gland, brain, and
      pituitary demonstrated a high expression levels. These data provide the primary
      foundation for further insights into the buffalo INSIG genes. 

PMID- 23860947
TI  - Antioxidant activities of some new chromonyl-2,4-thiazolidinediones and chromonyl
      2,4-imidazolidinediones having chromone cores.
AB  - The antioxidant properties of 11 new synthesized chromonyl-2,4-thiazolidinediones
      and chromonyl-2,4-imidazolidinediones (CBs) were investigated. The antioxidant
      activities and mechanisms of the CBs interaction with reactive oxygen species
      (ROS) were clarified using various in vitro antioxidant assay methods including
      superoxide anion radical (O2(*-)), hydroxyl radical (HO(*)), 1,1-diphenyl-2
      picryl-hydrazyl free radical (DPPH(*)) scavenging activity and the iron (II)
      ferrozine complex formation. The potassium superoxide/18-crown-6 ether dissolved
      in dimethylsulfoxide (DMSO) was applied as a source of superoxide anion radical.
      Hydroxyl radicals were produced in the Fenton-like reaction Fe(II)+H2O2.
      Chemiluminescence, spectrophotometry, and electron paramagnetic resonance (EPR)
      spectroscopy using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as spin trap were
      applied as the measurement techniques. The CBs examined that exhibited good free
      radical scavenging activity also showed strong total antioxidant power capacity.
      Possible mechanisms of antioxidation are proposed to explain the differences in
      the experimental results between the chromone derivatives with imidazolidine-2,4
      dione ring and those with thiazolidine-2,4-dione ring. In conclusion, some of the
      new CBs are promising to be applied as inhibitors of free radicals.

PMID- 23860949
TI  - Morphometric study of uninvolved rectal mucosa 10 cm and 20 cm away from the
      malignant tumor.
AB  - Recently, many details of the interplay between tumor cells and tumor-associated
      stromal elements leading to the progression of malignant disease were elucidated.
      In contrast, little is known about the role of uninvolved stromal tissue in the
      remote surrounding of the malignant tumor. Therefore, we performed a computer
      aided morphometric study of rectal mucosa in samples taken 10 cm and 20 cm away
      from the malignant tumor during endoscopic examination of 23 patients older than
      60 years. The samples of rectal mucosa from 10 healthy persons of corresponding
      age subjected to diagnostic rectoscopy during active screening for asymptomatic
      cancer were used as control. All structural elements of the rectal mucosa were
      studied and the number of nucleated cells in the lamina propria per 0.1 mm2 of
      tissue was assessed. Our study revealed a reduced number of cells in the lamina
      propria of the rectal mucosa 10 cm and 20 cm away from the tumor lesion in both
      male and female patients. The decreased mucosal height and increased crypt number
      were registered in female patients 10 cm away from the tumor. The connective
      tissue of lamina propria showed a disorderly organization: the collagen fibers
      were frail, loosely arranged and signs of tissue edema were present. Small blood
      vessels and capillaries were much more frequently seen than in healthy tissue.
      Our results demonstrate the complex interactions between the cancer and remote
      mucosal tissue of the affected organ.

PMID- 23860950
TI  - Exercise after diagnosis and metabolic syndrome among breast cancer survivors: a
      report from the Shanghai Breast Cancer Survival Study.
AB  - Metabolic syndrome (MetS) is an established risk factor for cardiovascular
      diseases and mortality. Limited data are available on the prevalence of MetS and
      its association with exercise among breast cancer survivors. The present study
      included 1,696 breast cancer survivors from the Shanghai Breast Cancer Survival
      Study, a population-based prospective cohort study conducted between April 2002
      and October 2011 in Shanghai, China. All women had a physical examination taken
      at study clinic approximately 60 months post-diagnosis. Exercise was assessed at
      approximately 6, 18, 36, and 60 months post-diagnosis. Information on medical
      history, tumor characteristics, cancer treatment, anthropometrics, and lifestyle
      was collected at study enrollment. Associations between exercise and MetS at 60
      months post-diagnosis were evaluated with multivariable logistic regression
      models. The mean age of the study population was 56.68 at 60-month survey, and
      the mean follow-up since cancer diagnosis was 63.66 months. The prevalence of
      MetS using National Cholesterol Education Program Adult Treatment Panel III
      criteria at approximately 60 months after diagnosis was 33.14%. Among overweight
      and obesity breast cancer survivors (body mass index (BMI) >= 25 kg/m(2) at
      baseline), the prevalence was 55.18%. The most common type of exercise in this
      population was walking (45.40%) at baseline. Exercise participation between 6 and
      60 months post-diagnosis was inversely associated with the prevalence of MetS
      with the adjusted odds ratio (OR) for exercise participation of >= 3.5 h/week (30
      min/day) being 0.69 (95% confidence interval (CI) 0.48-0.98). In addition
      consistent exercise participation reduced the prevalence of MetS (adjusted OR
      0.70 (95% CI 0.50-1.00). Associations of exercise with MetS were not modified by
      baseline waist circumference, BMI, comorbidity, baseline menopausal status, TNM
      stage, cancer treatment, or ER/PR status (p interactions > 0.05). Regular and
      persistent exercise after cancer diagnosis, even at low-to-moderate intensity
      level, decreases the prevalence of MetS among long-term breast cancer survivors.

PMID- 23860951
TI  - The protective effect of coffee consumption on cutaneous melanoma risk and the
      role of GSTM1 and GSTT1 polymorphisms.
AB  - PURPOSES: The authors examined the association between coffee consumption and
      cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms. METHODS:
      A hospital-based case-control study was conducted in the inpatient wards of IDI
      San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305
      controls. Information on socio-demographic characteristics, medical history,
      smoking, sun exposure, pigmentary characteristics and diet was collected for all
      subjects. Within the study, individual patterns at two polymorphic genes (GSTM1
      and GSTT1) belonging to glutathione S-transferases family were investigated in
      188 cases of cutaneous melanoma and 152 controls. Logistic regression was the
      method used to estimate odds ratio and 95 % confidence intervals. RESULTS: High
      frequency of coffee drinking (>once daily), compared with low-frequency
      consumption of coffee (<=7 times weekly) was associated with a protective effect
      for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age,
      education, hair colour, common nevi, skin phototype, and sunburn episodes in
      childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of
      coffee was extremely high for subjects with both GSTM1 and GSTT1 null
      polymorphisms (OR 0.01; 95 % CI 0.0003-0.54). CONCLUSIONS: Our results show a
      protective effect of coffee consumption for cutaneous melanoma, in particular for
      those with homozygous deletion for GSTM1 and GSTT1.

PMID- 23860952
TI  - Diabetes and prostate cancer screening in black and white men.
AB  - PURPOSE: Prior studies conducted primarily among white men find a reduced risk of
      prostate cancer associated with time since developing diabetes. While biologic
      explanations are plausible, the association may in part arise from more frequent
      prostate cancer screening among those with a diabetes diagnosis. The purpose of
      the present study was to investigate the association between diabetes and
      prostate cancer screening. METHODS: We examined differences in prostate cancer
      screening (prostate-specific antigen and/or digital rectal examination) testing
      practices after a diabetes diagnosis among lower-income persons living in the
      southeastern United States and enrolled in the Southern Community Cohort Study
      between 2002 and 2009. Baseline in-person interviews collected information on
      history of diabetes and prostate cancer screening from 18,809 black and 6,404
      white men aged 40-79 years. RESULTS: After adjustment for confounding, diabetic
      black [odds ratio (OR) 1.12, 95 % confidence interval (CI) 1.01-1.25] and white
      (OR 1.25, 95 % CI 1.03-1.51) men were more likely to undergo recent prostate
      cancer screening compared to non-diabetic men of the same race. The increased
      risk for prostate cancer screening, however, occurred primarily within the first
      12 months after diabetes diagnosis. CONCLUSIONS: Our results suggest that a
      diabetes diagnosis modestly increases the likelihood of having a prostate cancer
      screening test for both black and white men. The prevalence of screening was
      higher nearer to the time of diabetes diagnosis, which may contribute to an early
      increase in prostate cancer detection followed by lower prostate cancer detection
      after an extended time.

PMID- 23860953
TI  - Psychosocial stress and cigarette smoking persistence, cessation, and relapse
      over 9-10 years: a prospective study of middle-aged adults in the United States.
AB  - PURPOSE: Year-to-year decreases in smoking in the US have been observed only
      sporadically in recent years, which suggest a need for intensified efforts to
      identify those at risk for persistent smoking. To address this need, we examined
      the association between a variety of psychosocial stressors and smoking
      persistence, cessation, and relapse over 9-10 years among adults in the United
      States (n = 4,938, ages 25-74). METHODS: Using information provided at baseline
      and follow-up, participants were categorized as non-smokers, persistent smokers,
      ex-smokers, and relapsed smokers. Stressors related to relationships, finances,
      work-family conflict, perceived inequality, neighborhood, discrimination, and
      past-year family problems were assessed at baseline and follow-up. RESULTS: High
      stress at both assessments was associated with greater odds of persistent smoking
      for stressors related to relationships, finances, work, perceived inequality,
      past-year family problems, and a summary score. Among respondents who were
      smokers at baseline, high stress at both time points for relationship stress,
      perceived inequality, and past-year family problems was associated with nearly
      double the odds of failure to quit. CONCLUSIONS: Interventions to address
      psychosocial stress may be important components within smoking cessation efforts.

PMID- 23860955
TI  - Renal cyst completely filled with milk of calcium on CT appears as a simple cyst
      on sonography.
AB  - Milk of calcium within a renal cyst typically layers in the dependent aspect of
      the cyst and appears echogenic with posterior shadowing and reverberation echoes
      on sonography. We present a rare case of a renal cyst completely filled with milk
      of calcium, which appeared sonolucent with enhanced through transmission.

PMID- 23860956
TI  - Applicability of homeostasis model assessment of insulin resistance to patients
      with hyperglycemia.

PMID- 23860957
TI  - Applicability of homeostasis model assessment of insulin resistance to patients
      with hyperglycemia: reply to Kawada.

PMID- 23860959
TI  - Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class
      dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors.
AB  - PURPOSE: RO5126766, a highly selective dual Raf and MEK inhibitor, is a first-in
      class tandem mitogen-activated protein kinase signaling pathway inhibitor. The
      objectives of this phase I study were to determine maximum-tolerated dose (MTD)
      and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti
      tumor activity of RO5126766 in Japanese patients with advanced solid tumors.
      METHODS: Patients received a single oral dose of RO5126766 (0.8, 1.2, 1.8, or
      2.25 mg) followed by continuous once-daily dosing at the same dosage in 28-day
      cycles. A 3 + 3 dose-escalation design was used. PD was evaluated by pMEK and
      pERK inhibition in peripheral blood mononuclear cells (PBMCs). RESULTS: A total
      of 12 patients were enrolled in cohorts of 0.8, 1.2, 1.8, and 2.25 mg/day. In the
      dose range tested, no dose-limiting toxicity was observed, and therefore, MTD was
      not defined. Main adverse events included acneiform dermatitis, creatine
      phosphokinase elevation, and ocular disorders. The plasma exposure of RO5126766
      appeared to increase in a dose-proportional manner with a long plasma half-life
      (t 1/2) of 45.8-93.7 h. Following multiple dose administration, a steady-state
      condition was reached by Cycle 1 Day 8 (240 h). The inhibitory effects of
      RO5126766 on both pERK and pMEK in PBMCs increased in a dose-dependent manner.
      Five out of 12 patients achieved stable diseases, including a melanoma case with
      over 20 % shrinkage. CONCLUSIONS: RO5126766 has a manageable safety profile up to
      2.25 mg/day once daily with a favorable PK/PD profile in Japanese patients with
      advanced solid tumors.

PMID- 23860958
TI  - Compatibility of intravenous fosaprepitant with intravenous 5-HT3 antagonists and
      corticosteroids.
AB  - PURPOSE: Fosaprepitant dimeglumine for injection is the water-soluble
      phosphorylated prodrug of the neurokinin-1 receptor antagonist aprepitant. Both
      agents are approved (in combination with a 5-HT3 antagonist and a corticosteroid)
      for prevention of chemotherapy-induced nausea and vomiting. Because fosaprepitant
      is likely to be combined and stored in the same intravenous (IV) bag with 5-HT3
      antagonists and corticosteroids, the in vitro compatibility of fosaprepitant with
      these agents and other IV diluents was assessed. METHODS: Fosaprepitant (1 mg/mL
      in 0.9 % sodium chloride injection solution) was combined in binary or tertiary
      fashion with therapeutic-dose preparations of a 5-HT3 antagonist (ondansetron,
      granisetron, palonosetron, or tropisetron) and/or a corticosteroid (dexamethasone
      sodium phosphate or methylprednisolone sodium succinate). For diluent
      compatibility assessment, fosaprepitant was also prepared 1 mg/mL in 0.9 % sodium
      chloride injection solution, water for injection, or 5 % dextrose injection
      solution. After 24-h storage under ambient conditions, samples were assayed for
      degradation. RESULTS: Fosaprepitant demonstrated compatibility when combined in
      the same IV infusion bag with common 5-HT3 antagonists and corticosteroids for
      storage and IV coadministration, with the exception of palonosetron (incompatible
      under all experimental conditions) and tropisetron (incompatible unless combined
      with a corticosteroid). No incompatibility was observed between fosaprepitant and
      any of the 3 diluents tested. CONCLUSIONS: Use of fosaprepitant in combination
      with other antiemetics may provide a flexible option for administration of
      antiemetics to patients receiving moderately or highly emetogenic chemotherapy.

PMID- 23860960
TI  - Development of strategies for screening, predicting, and diagnosing intrauterine
      HBV infection in infants born to HBsAg positive mothers.
AB  - This study aimed at developing strategies for screening, predicting, and
      diagnosing intrauterine HBV infection in infants born to HBsAg positive mothers.
      A total of 1,360 infants born to 1,355 HBsAg positive mothers were followed for 1
      year. All newborn infants received active and passive immunization within 24 hr
      after birth. Maternal and infant blood samples were collected and tested for the
      status of serum HBsAg, HBeAg, and HBV DNA positivity. The accuracy of infant
      HBsAg positivity, HBV DNA positivity, HBsAg and HBV DNA double positivity, and
      HBsAg and/or HBV DNA positivity at birth in the diagnosis of intrauterine HBV
      infection was evaluated by receiver operating characteristic curve analysis. Of
      1,360 infants, 145 tested positive for HBsAg and/or HBV DNA at birth. Twenty-one
      (1.5%) infants, who were diagnosed with intrauterine HBV infection, showed HBsAg
      positivity from birth to 7 and 12 months of age. Infant HBsAg positivity at birth
      had the highest sensitivity in predicting intrauterine HBV infection, while
      neonatal HBsAg and HBV DNA double positivity had the highest specificity. These
      findings suggest that infants, who were born to HBsAg positive mothers and were
      positive for both HBsAg and HBV DNA at birth, may be at a higher risk for
      intrauterine HBV infection. HBsAg positivity at birth may be a good marker for
      screening intrauterine HBV infection. Infant HBsAg positivity both at birth and 7
      months of age may be used as a diagnostic criterion to simplify diagnostic
      procedures and improve diagnostic efficiency.

PMID- 23860961
TI  - Alprostadil plays a protective role in contrast-induced nephropathy in the
      elderly.
AB  - PURPOSE: To evaluate the protective effects of alprostadil on contrast-induced
      nephropathy (CIN) in elderly patients. METHODS: We randomized 370 patients into
      the control or alprostadil group. The patients in the control group were injected
      with 100 ml sterile saline and the patients in the alprostadil group with
      alprostadil (0.4 MUg/kg/day) in 100 ml sterile saline before and after iohexol
      enhanced (100 ml) computed tomography (CT). Serum creatinine (Scr), blood urea
      nitrogen (BUN), cystatin C (CysC), and creatinine clearance (Ccr) were analyzed
      or calculated. DeltaScr and DeltaCysC were determined by the changes between
      baseline and highest Scr and CysC levels. The standard for CIN was a postdose Scr
      increase >44.2 MUmol/l or >25 % over baseline. RESULTS: In the control group,
      peak Scr (P < 0.05) and DeltaScr (P < 0.01) were higher than those in the
      alprostadil group. The postdose CysC at 24 h (P < 0.05), 48 h (P < 0.05), and 72
      h (P < 0.05), peak CysC (P < 0.01), and DeltaCysC (P < 0.05) in the control group
      were higher than those in the alprostadil group. The incidence of CIN in the
      control group was 22.2 %, which was higher than in the alprostadil group (9.1 %,
      P < 0.01). Subgroup analyses in patients with advanced age (>= 80 years),
      concomitant hypertension or diabetes, and abnormal baseline renal function (Ccr
      <= 60 ml/min) showed that the alprostadil group had lower DeltaScr and DeltaCysC
      than the control group after contrast-enhanced CT examination in all four
      subgroups (P < 0.05 or P < 0.01). CONCLUSIONS: In this cohort of older patients
      undergoing contrast CT, the use of alprostadil reduced the incidence of CIN.

PMID- 23860962
TI  - Pseudomonas luteola peritonitis with favorable outcome in continuous peritoneal
      dialysis.

PMID- 23860963
TI  - Ferroportin in monocytes of hemodialysis patients and its associations with
      hepcidin, inflammation, markers of iron status and resistance to erythropoietin.
AB  - PURPOSE: Disturbed iron homeostasis contributes to resistance to recombinant
      human erythropoietin (rHuEpo) in hemodialysis (HD) patients. Increased hepcidin,
      which downregulates the iron exporter ferroportin, has been incriminated.
      However, other factors also control ferroportin expression in mononuclear
      phagocyte system. Ferroportin in monocytes, as well as serum hepcidin,
      interleukin-6 (IL-6) and common markers of iron status were measured and
      correlations with rHuEpo resistance index (ERI) were evaluated. METHODS: After a
      4-week washout period from iron treatment, 34 HD patients and 20 healthy
      volunteers enrolled in the study. Ferroportin was assessed by means of western
      blotting, whereas hepcidin and IL-6 with enzyme-linked immunosorbent assay.
      Hemoglobin, serum iron, ferritin and transferrin saturation (TSAT) were also
      measured. RESULTS: Ferroportin in monocytes of HD patients was decreased. Serum
      hepcidin and IL-6 were increased, whereas serum iron and TSAT were decreased. ERI
      was negatively correlated with ferroportin and all the markers of iron adequacy,
      but not with hepcidin. CONCLUSION: Decreased ferroportin in monocytes of HD
      patients accompanies increased hepcidin, inflammation, decreased iron
      availability and is correlated with resistance to rHuEpo treatment.

PMID- 23860964
TI  - Unrelated allogeneic bone marrow-derived mesenchymal stem cells for steroid
      refractory acute graft-versus-host disease: a phase I/II study.
AB  - We conducted a multicenter phase I/II study using mesenchymal stem cells (MSCs)
      manufactured from the bone marrow of healthy unrelated volunteers to treat
      steroid-refractory acute graft-versus-host disease (aGVHD). Fourteen patients
      with hematological malignancies who suffered from grade II (9 patients) or III
      aGVHD (5) were treated. Affected organs were gut (10 patients), skin (9
      patients), and liver (3 patients). Seven patients had two involved organs. The
      median age was 52. No other second-line agents were given. MSCs were given at a
      dose of 2 * 10(6) cells/kg for each infusion twice a week for 4 weeks. If needed,
      patients were continuously given MSCs weekly for an additional 4 weeks. By week
      4, 13 of 14 patients (92.9 %) had responded to MSC therapy with a complete
      response (CR; n = 8) or partial response (PR; n = 5). At 24 weeks, 11 patients
      (10 with CR and 1 with PR) were alive. At 96 weeks, 8 patients were alive in CR.
      A total of 6 patients died, attributable to the following: underlying disease
      relapse (2 patients), breast cancer relapse (1), veno-occlusive disease (1),
      ischemic cholangiopathy (1), and pneumonia (1). No clear adverse effects
      associated with MSC infusion were observed. Third party-derived bone marrow MSCs
      may be safe and effective for patients with steroid-refractory aGVHD. 

PMID- 23860965
TI  - Breakage of transgenic tobacco roots for monoclonal antibody release in an ultra
      scale down shearing device.
AB  - Transgenic tobacco roots offer a potential alternative to leaves for monoclonal
      antibody (MAb) production. A possible method for extraction of MAbs from roots is
      by homogenization, breaking the roots into fragments to release the antibody.
      This process was assessed by shearing 10 mm root sections ("roots") in a 24 mL
      ultra-scale down shearing device, including an impeller with serrated blade
      edges, intended to mimic the action of a large-scale homogenizer. Size
      distributions of the remaining intact roots and root fragments were obtained as a
      function of shearing time. The data suggest that about 36% of the roots could not
      be broken under the prevailing conditions and, beyond these unbreakable roots,
      the fragmentation was approximately first order with respect to intact root
      number. It was postulated that root breakage in such a high shearing device was
      due to root-impeller collisions and the particle size data suggest that roots
      colliding with the impeller were completely fragmented into debris particles of
      the order of 0.1 mm in length. IgG release normalized to release by grinding
      appeared to lag behind the number of roots that had fragmented, suggesting that a
      process of leakage followed fragmentation in the ultra-scale down shearing
      device.

PMID- 23860969
TI  - Juan de Pareja: Diego Rodriguez de Silva y Velazquez.

PMID- 23860970
TI  - Panel recommends easing restrictions on rosiglitazone despite concerns about
      cardiovascular safety.

PMID- 23860966
TI  - Fabry disease practice guidelines: recommendations of the National Society of
      Genetic Counselors.
AB  - Identification and comprehensive care of individuals who have Fabry disease (FD)
      requires a multidisciplinary approach inclusive of genetic testing, test
      interpretation, genetic counseling, long term disease symptom monitoring,
      treatment recommendations, and coordination of therapy. The purpose of this
      document is to provide health care professionals with guidelines for testing,
      care coordination, identification of psychosocial issues, and to facilitate a
      better understanding of disease treatment expert recommendations for patients
      with Fabry disease. These recommendations are the opinions of a multicenter
      working group of genetic counselors, medical geneticists, and other health
      professionals with expertise in Fabry disease counseling, as well as
      representatives/founders of the two United States based Fabry disease patient
      advocacy groups who are themselves affected by Fabry disease. The recommendations
      are U.S. Preventive Task Force Class III, and they are based on clinical
      experience, a review of pertinent English-language articles, and reports of
      expert committees. This document reviews the genetics of Fabry disease, the
      indications for genetic testing, interpretation of results, psychosocial
      considerations, and references to professional and patient resources. 

PMID- 23860971
TI  - FDA: Thrombosis risk with immune globulin products.

PMID- 23860972
TI  - Alliance aims for standardized, shareable genomic data.

PMID- 23860981
TI  - The international registry infrastructure for cardiovascular device evaluation
      and surveillance.

PMID- 23860982
TI  - New incentive-based programs: Maryland's health disparities initiatives.

PMID- 23860983
TI  - A piece of my mind. Interpreters or teachers?

PMID- 23860984
TI  - West Nile virus: too important to forget.

PMID- 23860985
TI  - Vasopressin, steroids, and epinephrine and neurologically favorable survival
      after in-hospital cardiac arrest: a randomized clinical trial.
AB  - IMPORTANCE: Among patients with cardiac arrest, preliminary data have shown
      improved return of spontaneous circulation and survival to hospital discharge
      with the vasopressin-steroids-epinephrine (VSE) combination. OBJECTIVE: To
      determine whether combined vasopressin-epinephrine during cardiopulmonary
      resuscitation (CPR) and corticosteroid supplementation during and after CPR
      improve survival to hospital discharge with a Cerebral Performance Category (CPC)
      score of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest. DESIGN,
      SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel
      group trial performed from September 1, 2008, to October 1, 2010, in 3 Greek
      tertiary care centers (2400 beds) with 268 consecutive patients with cardiac
      arrest requiring epinephrine according to resuscitation guidelines (from 364
      patients assessed for eligibility). INTERVENTIONS: Patients received either
      vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration
      approximately 3 minutes) (VSE group, n = 130) or saline placebo plus epinephrine
      (1 mg/CPR cycle; cycle duration approximately 3 minutes) (control group, n = 138)
      for the first 5 CPR cycles after randomization, followed by additional
      epinephrine if needed. During the first CPR cycle after randomization, patients
      in the VSE group received methylprednisolone (40 mg) and patients in the control
      group received saline placebo. Shock after resuscitation was treated with stress
      dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE
      group, n = 76) or saline placebo (control group, n = 73). MAIN OUTCOMES AND
      MEASURES: Return of spontaneous circulation (ROSC) for 20 minutes or longer and
      survival to hospital discharge with a CPC score of 1 or 2. RESULTS: Follow-up was
      completed in all resuscitated patients. Patients in the VSE group vs patients in
      the control group had higher probability for ROSC of 20 minutes or longer
      (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio [OR], 2.98; 95% CI, 1.39-6.40; P =
      .005) and survival to hospital discharge with CPC score of 1 or 2 (18/130 [13.9%]
      vs 7/138 [5.1%]; OR, 3.28; 95% CI, 1.17-9.20; P = .02). Patients in the VSE group
      with postresuscitation shock vs corresponding patients in the control group had
      higher probability for survival to hospital discharge with CPC scores of 1 or 2
      (16/76 [21.1%] vs 6/73 [8.2%]; OR, 3.74; 95% CI, 1.20-11.62; P = .02), improved
      hemodynamics and central venous oxygen saturation, and less organ dysfunction.
      Adverse event rates were similar in the 2 groups. CONCLUSION AND RELEVANCE: Among
      patients with cardiac arrest requiring vasopressors, combined vasopressin
      epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in
      postresuscitation shock, compared with epinephrine/saline placebo, resulted in
      improved survival to hospital discharge with favorable neurological status. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00729794.

PMID- 23860986
TI  - Association between duration of overall and abdominal obesity beginning in young
      adulthood and coronary artery calcification in middle age.
AB  - IMPORTANCE: Younger individuals are experiencing a greater cumulative exposure to
      excess adiposity over their lifetime. However, few studies have determined the
      consequences of long-term obesity. OBJECTIVE: To examine whether the duration of
      overall and abdominal obesity was associated with the presence and 10-year
      progression of coronary artery calcification (CAC), a subclinical predictor of
      coronary heart disease. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of
      3275 white and black adults aged 18 to 30 years at baseline in 1985-1986 who did
      not initially have overall obesity (body mass index [BMI] >=30) or abdominal
      obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the
      multicenter, community-based Coronary Artery Risk Development in Young Adults
      (CARDIA) study. Participants completed computed tomography scanning for the
      presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration
      of overall and abdominal obesity was calculated using repeat measurements of BMI
      and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline.
      MAIN OUTCOMES AND MEASURES: Presence of CAC was measured by computed tomography
      at the year 15 (2000-2001), year 20 (2005-2006), or year 25 (2010-2011) follow-up
      examinations. Ten-year progression of CAC (2000-2001 to 2010-2011) was defined as
      incident CAC in 2010-2011 or an increase in CAC score of 20 Agatston units or
      greater. RESULTS: During follow-up, 40.4% and 41.0% developed overall and
      abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher
      for those who experienced more than 20 years vs 0 years of overall obesity (16.0
      vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2%
      and 27.7% of those with more than 20 years of overall and abdominal obesity,
      respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0
      years. After adjustment for BMI or WC and potential confounders, the hazard
      ratios for CAC for each additional year of overall or abdominal obesity were 1.02
      (95% CI, 1.01-1.03) and 1.03 (95% CI, 1.02-1.05), respectively. The adjusted odds
      ratios for CAC progression were 1.04 (95% CI, 1.01-1.06) and 1.04 (95% CI, 1.01
      1.07), respectively. Associations were attenuated but largely persisted following
      additional adjustment for potential intermediate metabolic factors during follow
      up. CONCLUSIONS AND RELEVANCE: Longer duration of overall and abdominal obesity
      was associated with subclinical coronary heart disease and its progression
      through midlife independent of the degree of adiposity. Preventing or at least
      delaying the onset of obesity in young adulthood may lower the risk of developing
      atherosclerosis through middle age.

PMID- 23860987
TI  - Androgen deprivation therapy and risk of acute kidney injury in patients with
      prostate cancer.
AB  - IMPORTANCE: The use of androgen deprivation therapy (ADT) in the treatment of
      advanced prostate cancer has been shown to delay the clinical progression of the
      disease. However, the testosterone suppression associated with this therapy may
      lead to a hypogonadal condition that can have detrimental effects on renal
      function, thus raising the hypothesis that ADT-induced hypogonadism could
      potentially lead to acute kidney injury (AKI). OBJECTIVE: To determine whether
      the use of ADT is associated with an increased risk of AKI in patients newly
      diagnosed with prostate cancer. DESIGN AND SETTING: A nested case-control
      analysis using medical information extracted from the UK Clinical Practice
      Research Datalink linked to the Hospital Episodes Statistics database.
      PARTICIPANTS: Men newly diagnosed with nonmetastatic prostate cancer between
      January 1, 1997, and December 31, 2008, were selected and followed up until
      December 31, 2009. Cases were patients with incident AKI during follow-up who
      were randomly matched with up to 20 controls on age, calendar year of prostate
      cancer diagnosis, and duration of follow-up. MAIN OUTCOMES AND MEASURES:
      Conditional logistic regression was used to estimate odds ratios (ORs) with 95%
      CIs of AKI associated with the use of ADT. ADT was categorized into 1 of 6
      mutually exclusive groups: gonadotropin-releasing hormone agonists, oral
      antiandrogens, combined androgen blockade, bilateral orchiectomy, estrogens, and
      combination of the above. RESULTS A total of 10,250 patients met the study
      inclusion criteria. During a mean follow-up of 4.1 (SD, 2.9) years, 232 incident
      cases of AKI were identified (rate, 5.5/1000 person-years). Overall, current use
      of any ADT was associated with an increased risk of AKI when compared with never
      use (OR, 2.48 [95% CI, 1.61-3.82]), generating a rate difference of 4.43/1000
      persons per year (95% CI, 1.54-7.33). This association was mainly driven by a
      combined androgen blockade consisting of gonadotropin-releasing hormone agonists
      with oral antiandrogens (OR, 4.50 [95% CI, 2.61-7.78]), estrogens (OR, 4.00 [95%
      CI, 1.06-15.03]), other combination therapies (OR, 4.04 [95% CI, 1.88-8.69]), and
      gonadotropin-releasing hormone agonists (OR, 1.93 [95% CI, 1.20-3.10]).
      CONCLUSIONS AND RELEVANCE: In a cohort of patients with newly diagnosed
      nonmetastatic prostate cancer, the use of ADT was significantly associated with
      an increased risk of AKI. These findings require replication in other well
      designed studies as well as further investigation of their clinical importance.

PMID- 23860988
TI  - The 2012 West Nile encephalitis epidemic in Dallas, Texas.
AB  - IMPORTANCE: After progressive declines over recent years, in 2012 West Nile virus
      epidemics resurged nationwide, with the greatest number of cases centered in
      Dallas County, Texas. OBJECTIVE: To analyze the epidemiologic, meteorologic, and
      geospatial features of the 2012 Dallas West Nile virus epidemic to guide future
      prevention efforts. DESIGN, SETTING, AND PATIENTS: Public health surveillance of
      Dallas County, an area of 2257 km2 and population of 2.4 million. Surveillance
      data included numbers of residents diagnosed with West Nile virus infection
      between May 30, 2012, and December 3, 2012; mosquito trap results; weather data;
      and syndromic surveillance from area emergency departments. MAIN OUTCOMES AND
      MEASURES: Incidence and age-adjusted incidence rates of West Nile neuroinvasive
      disease (WNND), daily prevalence of emergency department visits for asthma and
      skin rash, and Culex quinquefasciatus species-specific vector index (an estimate
      of the average number of West Nile virus-infected mosquitoes per trap-night).
      RESULTS: The investigation identified 173 cases of WNND, 225 of West Nile fever,
      17 West Nile virus-positive blood donors, and 19 deaths in 2012. The incidence
      rate for WNND was 7.30 per 100,000 residents in 2012, compared with 2.91 per
      100,000 in 2006, the largest previous Dallas County outbreak. An unusually rapid
      and early escalation of large numbers of human cases closely followed increasing
      infection trends in mosquitoes. The Cx quinquefasciatus species-specific vector
      index predicted the onset of symptoms among WNND cases 1 to 2 weeks later (count
      regression beta = 2.97 [95% CI, 2.34 to 3.60]; P < .001). Although initially
      widely distributed, WNND cases soon clustered in neighborhoods with high housing
      density in the north central area of the county, reflecting higher vector indices
      and following geospatial patterns of West Nile virus in prior years. During the
      11 years since West Nile virus was first identified in Dallas, the log
      transformed annual prevalence of WNND was inversely associated with the number of
      days with low temperatures below 28 degrees F (-2.2 degrees C) in December
      through February (beta = -0.29 [95% CI, -0.36 to -0.21]; P < .001). Aerial
      insecticide spraying was not associated with increases in emergency department
      visits for respiratory symptoms (beta = -4.03 [95% CI, -13.76 to 5.70]; P = .42)
      or skin rash (beta = -1.00 [95% CI, -6.92 to 4.92]; P = .74). CONCLUSIONS AND
      RELEVANCE: Large West Nile virus epidemics in Dallas County begin early after
      unusually warm winters, revisit similar geographical distributions, and are
      strongly predicted by the mosquito vector index. Consideration of weather
      patterns and historical geographical hot spots and acting on the vector index may
      help prevent West Nile virus-associated illness.

PMID- 23860990
TI  - Does rigorous quality process reporting guarantee superior-quality health care?

PMID- 23860989
TI  - West Nile virus: review of the literature.
AB  - IMPORTANCE: Since its introduction in North America in 1999, West Nile virus has
      produced the 3 largest arboviral neuroinvasive disease outbreaks ever recorded in
      the United States. OBJECTIVE: To review the ecology, virology, epidemiology,
      clinical characteristics, diagnosis, prevention, and control of West Nile virus,
      with an emphasis on North America. EVIDENCE REVIEW: PubMed electronic database
      was searched through February 5, 2013. United States national surveillance data
      were gathered from the Centers for Disease Control and Prevention. FINDINGS: West
      Nile virus is now endemic throughout the contiguous United States, with 16,196
      human neuroinvasive disease cases and 1549 deaths reported since 1999. More than
      780,000 illnesses have likely occurred. To date, incidence is highest in the
      Midwest from mid-July to early September. West Nile fever develops in
      approximately 25% of those infected, varies greatly in clinical severity, and
      symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute
      flaccid paralysis) develops in less than 1% but carries a fatality rate of
      approximately 10%. Encephalitis has a highly variable clinical course but often
      is associated with considerable long-term morbidity. Approximately two-thirds of
      those with paralysis remain with significant weakness in affected limbs.
      Diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal
      fluid. Treatment is supportive; no licensed human vaccine exists. Prevention uses
      an integrated pest management approach, which focuses on surveillance,
      elimination of mosquito breeding sites, and larval and adult mosquito management
      using pesticides to keep mosquito populations low. During outbreaks or impending
      outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the
      abundance of infected, biting mosquitoes. Pesticide exposure and adverse human
      health events following adult mosquito control operations for West Nile virus
      appear negligible. CONCLUSIONS AND RELEVANCE: In North America, West Nile virus
      has and will remain a formidable clinical and public health problem for years to
      come.

PMID- 23860991
TI  - Survival after multiple hospitalizations for infections and dehydration in
      nursing home residents with advanced cognitive impairment.

PMID- 23860992
TI  - Long-term follow-up of young adults with stroke.

PMID- 23860993
TI  - Long-term follow-up of young adults with stroke.

PMID- 23860994
TI  - Long-term follow-up of young adults with stroke--reply.

PMID- 23860995
TI  - Smoking cessation, weight change, and risk of cardiovascular disease.

PMID- 23860996
TI  - Population health and accountable care organizations.

PMID- 23860997
TI  - Smoking cessation, weight change, and risk of cardiovascular disease--reply.

PMID- 23861000
TI  - Population health and accountable care organizations--reply.

PMID- 23861002
TI  - Comparative mortality of married and single persons.

PMID- 23861003
TI  - JAMA patient page. Safety of aerial pesticide spraying for mosquitoes.

PMID- 23861004
TI  - Memory suppression can help people "unlearn" behavioral responses--but only for
      nonemotional memories.
AB  - When encountering reminders of memories that we prefer not to think about, we
      often try to exclude those memories from awareness. Past studies have revealed
      that such suppression attempts can reduce the subsequent recollection of unwanted
      memories. In the present study, we examined whether the inhibitory effects extend
      even to associated behavioral responses. Participants learned cue-target pairs
      for emotional and nonemotional targets and were additionally trained in
      behavioral responses for each cue. Afterward, they were shown the cues and
      instructed either to think or to avoid thinking about the targets without
      performing any behaviors. In a final test phase, behavioral performance was
      tested for all of the cues. When the targets were neutral, participants' attempts
      to avoid retrieval reduced accuracy and increased reaction times in generating
      behavioral responses associated with cues. By contrast, behavioral performance
      was not affected by suppression attempts when the targets were emotional. These
      results indicate that controlling unwanted recollection is powerful enough to
      inhibit associated behavioral responses-but only for nonemotional memories. 

PMID- 23861007
TI  - Metal nanoparticles for nano-imaging and nano-analysis.
AB  - Metal nanoparticles have recently emerged as ubiquitous surface-enhanced Raman
      scattering (SERS) agents for nano-imaging and nano-analysis. These applications
      make use of the unique optical properties of metal nanoparticles to enhance the
      efficiency of Raman scattering, whereas the small size of the nanoparticles
      localizes the enhanced Raman scattering at the nanoscale. In this perspective, we
      review the recent progress in SERS nano-imaging and nano-spectroscopy using metal
      nanoparticles applied especially to biological samples and nanomaterials. For
      biosamples, the highly sensitive molecular SERS detection capability of metal
      nanoparticles is used to analyze intracellular molecules. For analysis of
      nanomaterials, an innovative approach called tip-enhanced Raman scattering (TERS)
      microscopy, where metal nanoparticles are used with an AFM cantilever, has proven
      to be extremely powerful for nano-imaging. The precise control and analysis of
      the interaction between the metal and the sample are thus the key to overcome the
      limitations of current microscopic and spectroscopic techniques, and to guide
      future developments. 

PMID- 23861008
TI  - Modulation of protein stability and aggregation properties by surface charge
      engineering.
AB  - An attempt to alter protein surface charges through traditional protein
      engineering approaches often affects the native protein structure significantly
      and induces misfolding. This limitation is a major hindrance in modulating
      protein properties through surface charge variations. In this study, as a
      strategy to overcome such a limitation, we attempted to co-introduce stabilizing
      mutations that can neutralize the destabilizing effect of protein surface charge
      variation. Two sets of rational mutations were designed; one to increase the
      number of surface charged amino acids and the other to decrease the number of
      surface charged amino acids by mutating surface polar uncharged amino acids and
      charged amino acids, respectively. These two sets of mutations were introduced
      into Green Fluorescent Protein (GFP) together with or without stabilizing
      mutations. The co-introduction of stabilizing mutations along with mutations for
      surface charge modification allowed us to obtain functionally active protein
      variants (s-GFP(+15-17) and s-GFP(+5-6)). When the protein properties such as
      fluorescent activity, folding rate and kinetic stability were assessed, we found
      the possibility that the protein stability can be modulated independently of
      activity and folding by engineering protein surface charges. The aggregation
      properties of GFP could also be altered through the surface charge engineering. 

PMID- 23861009
TI  - Preparation, characterization, and insecticidal activity evaluation of three
      different formulations of Beauveria bassiana against Musca domestica.
AB  - Three formulations; bait, encapsulation, and emulsion of Beauveria bassiana were
      prepared and evaluated for their insecticidal activity in simulated field
      settings. Tea waste-based bait formulation of B. bassiana showed 100% mortality
      (within 72 h) in lab assay against adult houseflies. In field assay using traps,
      65% relative entrapment and 100 % mortality (within 60 h) of entrapped flies was
      observed. Although the bait formulation was low cost and easy to prepare and
      transport, its storage ability was limited. Hence, more advanced formulations in
      form of encapsulation and emulsion was attempted. Encapsulated B. bassiana
      conidia (using skimmed milk powder, polyvinyl pyrrolidone K-90 and glucose as
      additives) showed 100% conidial germination and retained 78% conidial viability,
      even after storage for 12 months at 30  degrees C. Encapsulated product showed
      54.8% (freshly prepared) and 30.6 % (after 12-months storage) mortality of
      housefly larvae in a simulated field condition. Emulsion formulation was prepared
      by using Tween 20 as surfactant with seven vegetable oils: soybean, rapeseed,
      sunflower, olive, castor, til, and linseed. Emulsion with linseed oil showing
      maximum conidial germination (94%) was evaluated for shelf life and pathogenecity
      against housefly larvae. Shelf life analysis of emulsion revealed 28% conidial
      germination and 19.9% housefly larval mortality after 12 months of storage as
      opposed to 94% conidial germination and 51.7% of larval mortality with fresh
      product. Significant increase in shelf * targeted application of formulation is
      expected to increase its mass applicability for housefly control. Also, the
      variability among products presents diverse opportunities for commercialization.

PMID- 23861010
TI  - Robust k-mer frequency estimation using gapped k-mers.
AB  - Oligomers of fixed length, k, commonly known as k-mers, are often used as
      fundamental elements in the description of DNA sequence features of diverse
      biological function, or as intermediate elements in the constuction of more
      complex descriptors of sequence features such as position weight matrices. k-mers
      are very useful as general sequence features because they constitute a complete
      and unbiased feature set, and do not require parameterization based on incomplete
      knowledge of biological mechanisms. However, a fundamental limitation in the use
      of k-mers as sequence features is that as k is increased, larger spatial
      correlations in DNA sequence elements can be described, but the frequency of
      observing any specific k-mer becomes very small, and rapidly approaches a sparse
      matrix of binary counts. Thus any statistical learning approach using k-mers will
      be susceptible to noisy estimation of k-mer frequencies once k becomes large.
      Because all molecular DNA interactions have limited spatial extent, gapped k-mers
      often carry the relevant biological signal. Here we use gapped k-mer counts to
      more robustly estimate the ungapped k-mer frequencies, by deriving an equation
      for the minimum norm estimate of k-mer frequencies given an observed set of
      gapped k-mer frequencies. We demonstrate that this approach provides a more
      accurate estimate of the k-mer frequencies in real biological sequences using a
      sample of CTCF binding sites in the human genome.

PMID- 23861011
TI  - Myxoid liposarcoma of the spermatic cord: US and MR imaging findings.
AB  - We report a patient with myxoid liposarcoma of the spermatic cord in whom
      combined use of both ultrasound (US) and MRI helped to suggest the diagnosis. The
      lesion was solid at US and vascularized at color Doppler. T1-weighted MRI did not
      show fat within it; on T2-weighted images it had high signal intensity, with a
      cyst-like appearance. It is known that fat-poor myxoid liposarcomas with high
      water content may mimic a cystic lesion on non-contrast-enhanced MR; then, a
      combination of MRI findings, suggesting a cyst, and of US findings, showing the
      mass was actually solid and vascularized, allowed preoperatively the diagnosis of
      fat-poor myxoid liposarcoma.

PMID- 23861012
TI  - Erroneous gambling-related beliefs as illusions of primary and secondary control:
      a confirmatory factor analysis.
AB  - Different classification systems for erroneous beliefs about gambling have been
      proposed, consistently alluding to 'illusion of control' and 'gambler's fallacy'
      categories. None of these classification systems have, however, considered the
      how the illusion of control and the gambler's fallacy might be interrelated. In
      this paper, we report the findings of a confirmatory factor analysis that
      examines the proposal that most erroneous gambling-related beliefs can be defined
      in terms of Rothbaum et al.'s (J Pers Soc Psychol, doi: 10.1037/0022-3514.42.1.5
      , 1982) distinction between 'primary' and 'secondary' illusory control, with the
      former being driven to a large extent by the well-known gambler's fallacy and the
      latter being driven by a complex of beliefs about supernatural forces such as God
      and luck. A survey consisting of 100 items derived from existing instruments was
      administered to 329 participants. The analysis confirmed the existence of two
      latent structures (beliefs in primary and secondary control), while also offering
      support to the idea that gambler's fallacy-style reasoning may underlie both
      perceived primary control and beliefs about the cyclical nature of luck, a form
      of perceived secondary control. The results suggest the need for a greater focus
      on the role of underlying processes or belief structures as factors that foster
      susceptibility to specific beliefs in gambling situations. Addressing and
      recognising the importance of these underlying factors may also have implications
      for cognitive therapy treatments for problem gambling. 

PMID- 23861013
TI  - Novel deletion in glycoprotein G forms a cluster and causes epidemiologic spread
      of herpes simplex virus type 2 infection.
AB  - The herpes simplex virus type 2 (HSV-2) glycoprotein G (gG-2) gene of 106
      clinical isolates was analyzed and six isolates were identified with 63
      nucleotides comprising 21 amino acids (aa) deleted in the immunodominant region.
      Compared with strain HG52, variations in the gG-2 gene were found at 276 and 27
      sites in nucleotide and aa sequences, respectively, in the 106 strains.
      Significant variations in both nucleotides and aa were accumulated in the
      immunodominant region rather than in the other regions (P < 0.001), indicating
      that the immunodominant region might be indispensable in vivo and a hot spot for
      variation. The frequency of 21 aa-deleted strains (HSVDelta21/gG-2) among
      clinical isolates was 5%, indicating the advantage of this deletion of gG-2 for
      epidemiological expansion. Phylogenetic analysis of the 106 strains indicated
      that the HSVDelta21/gG-2 strains formed a cluster among the various variations
      but that their genomes showed different endonuclease digestion patterns. The
      antibody titers to total HSV antigens of patients infected with wild HSV-2 and
      HSVDelta21/gG-2 were similar, but patients with HSVDelta21/gG-2 had a lower
      antibody titer to gG-2 than those with wild HSV-2 (P < 0.001). HSVDelta21/gG-2
      might be less immnunogenic and reduce antibody production to gG-2, while its
      pathogenicity in humans was not distinguished in its clinical manifestations.
      Thus, infection with HSVDelta21/gG-2 caused genital lesions similar to wild HSV-2
      infection, but evaded the immune response to gG-2 to allow epidemiological
      spread, indicating the importance of this deletion in the immunodominant region
      of gG-2 in the pathogenesis and transmission of genital herpes.

PMID- 23861014
TI  - H2 interaction with divalent cations in isostructural MOFs: a key study for
      variable temperature infrared spectroscopy.
AB  - Systematic studies of H2 adsorption by variable temperature infrared (VTIR)
      spectroscopy have added value in the characterization of hydrogen storage
      materials. As a key study to describe the potential of the method, here we report
      VTIR spectroscopy results of H2 adsorption at isostructural MOFs CPO-27-M (M =
      Mg, Mn, Co, Ni, Zn). The strongest perturbation of H2 vibrational frequency is
      due to the interaction with an open metal site. Although ionic radius is an
      empirical value, the direct correlation between ionic radii of the metal cation
      and H2 interaction energy is found in MOFs of the same topology. The highest
      enthalpy of hydrogen adsorption 15 +/- 1 kJ mol(-1) was found for Ni(2+). VTIR
      results of H2 adsorption at isostructural MOFs CPO-27-M (M = Mg, Mn, Co, Ni, Zn)
      were compared with data obtained from analogous studies performed on a large
      variety of microporous materials (MOFs and zeolites), underlining the relevance
      of the approach to get reliable energetic and entropic (DeltaH(0) and DeltaS(0))
      values to be compared with computational data and isosteric heats. 

PMID- 23861015
TI  - Padma 28 for intermittent claudication.
AB  - BACKGROUND: Intermittent claudication is pain caused by chronic occlusive
      arterial disease that develops in a limb during exercise and is relieved with
      rest. Most drug treatments of intermittent claudication have a limited effect in
      improving walking distance. Padma 28, a Tibetan herbal preparation, has been used
      to treat intermittent claudication, but there is debate as to whether Padma 28
      produces a clinical benefit beyond the placebo effect. OBJECTIVES: To determine
      whether Padma 28 is effective, compared with placebo or other medications, in
      increasing pain-free and maximum walking distance for patients with intermittent
      claudication. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group
      Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched
      April 2013), CENTRAL (2013, Issue 3) and clinical trials databases. In addition,
      a pharmaceutical company was contacted. SELECTION CRITERIA: Randomised controlled
      trials of Padma 28 compared with placebo or other pharmacological treatments in
      people suffering from intermittent claudication. DATA COLLECTION AND ANALYSIS:
      All review authors independently assessed the selected studies and extracted the
      data. Risk of bias was evaluated independently by two review authors. Depending
      on the data provided in the individual trials, we extracted mean or median
      walking distance at the end of the trial, or change in walking distance over the
      course of the trial, or both. Where not provided, and whenever possible, the
      statistical significance of differences in these parameters between treatment and
      placebo groups in individual trials was calculated. Where possible, data were
      combined by meta-analysis. MAIN RESULTS: Five trials involving 365 participants
      were identified. All trials compared Padma 28 with placebo for at least 16 weeks
      of follow-up. Pain-free and maximum walking distances both increased
      significantly in the groups treated with Padma 28, with no significant change in
      the placebo group. In general, the studies presented results comparing the
      treatment arms before and after treatment but made no comparisons between the
      Padma 28 and placebo groups. Pooled data of maximum walking distance after
      treatment with Padma 28 and placebo from two studies indicated a statistically
      significant difference in maximum walking distance (mean difference (MD) 95.97 m,
      95% confidence interval (CI) 79.07 m to 112.88 m, P < 0.00001). The clinical
      importance of these observed changes in walking distance is unclear as no quality
      of life data were reported. There was no effect on ankle brachial index. Mild
      side effects, especially gastrointestinal discomfort, tiredness and skin
      eruption, were reported but this outcome was not statistically significantly
      different between the groups (odds ratio (OR) 1.09, 95% CI 0.42 to 2.83, P =
      0.86). AUTHORS' CONCLUSIONS: Some evidence exists from individual trials to
      suggest that Padma 28 may be effective in increasing walking distances, at least
      in the short term (four months), in people with intermittent claudication. Side
      effects do not appear to be a problem. However, the longer term effects of
      treatment are unknown and the clinical significance of the improvements in
      walking distance are questionable. Moreover, the quality of the evidence is
      limited by the small sample size of the available trials, lack of detail on key
      elements required to assess sources of bias, such as around randomisation and
      blinding, limited reporting of statistical analyses that compared treatment
      groups, and relatively high withdrawal rates that were linked to the outcome that
      is patients were withdrawn if they failed to improve walking distance. There was
      also evidence of publication bias. We therefore feel there is currently
      insufficient evidence to support the use of Padma 28 in the routine management of
      intermittent claudication. Further well-designed research would be required to
      determine the true effects of this herbal preparation.

PMID- 23861016
TI  - Matching tumor risk with aggressiveness of treatment in men with multiple
      comorbidities and early-stage prostate cancer.
AB  - BACKGROUND: Men with multiple comorbidities are often overtreated for low-risk
      prostate cancer, but it is unclear whether they are undertreated for high-risk
      cancer, which has appreciable short-term prostate cancer-specific mortality. This
      study characterized the impact of comorbidity on treatment and survival in men
      with differing tumor risks. METHODS: The researchers sampled 1482 men with
      nonmetastatic prostate cancer at 2 Veterans Affairs hospitals between 1998 and
      2004, using multivariate probit regression to determine probabilities of
      aggressive treatment among men with differing Charlson comorbidity scores within
      D'Amico tumor risk strata. Using competing-risks regression, a comparison was
      made of 8-year cancer-specific mortality for men treated aggressively and
      nonaggressively among Charlson score-tumor risk pairs. RESULTS: The study sample
      comprised 516 men (36%) with low-risk, 475 men (33%) with intermediate-risk, and
      432 men (30%) with high-risk prostate cancer. Men with high-risk disease tended
      to have lower probability of aggressive treatment than other risk strata,
      regardless of comorbidity. Among men with Charlson scores 3+, probabilities of
      aggressive treatment did not increase with higher tumor risk (0.48, 0.61, 0.49
      for low-, intermediate-, and high-risk disease, respectively). In competing-risks
      analysis, aggressive treatment was not associated with cancer-specific survival
      benefit in men with multiple comorbidities (Charlson scores of 2 or 3+) and low-
      and intermediate-risk disease, but there was a strong trend toward survival
      advantage in such men with high-risk disease. CONCLUSIONS: Aggressiveness of
      treatment is poorly matched with tumor risk in men with significant comorbidity.
      Men with major comorbidities should consider conservative management for low- and
      intermediate-risk disease and aggressive treatment for high-risk disease.

PMID- 23861017
TI  - Expression of chicken parvovirus VP2 in chicken embryo fibroblasts requires codon
      optimization for production of naked DNA and vectored meleagrid herpesvirus type
      1 vaccines.
AB  - Meleagrid herpesvirus type 1 (MeHV-1) is an ideal vector for the expression of
      antigens from pathogenic avian organisms in order to generate vaccines. Chicken
      parvovirus (ChPV) is a widespread infectious virus that causes serious disease in
      chickens. It is one of the etiological agents largely suspected in causing
      Runting Stunting Syndrome (RSS) in chickens. Initial attempts to express the wild
      type gene encoding the capsid protein VP2 of ChPV by insertion into the thymidine
      kinase gene of MeHV-1 were unsuccessful. However, transient expression of a codon
      optimized synthetic VP2 gene cloned into the bicistronic vector pIRES2-Ds-Red2,
      could be demonstrated by immunocytochemical staining of transfected chicken
      embryo fibroblasts (CEFs). Red fluorescence could also be detected in these
      transfected cells since the red fluorescent protein gene is downstream from the
      internal ribosome entry site (IRES). Strikingly, fluorescence could not be
      demonstrated in cells transiently transfected with the bicistronic vector
      containing the wild-type or non-codon-optimized VP2 gene. Immunocytochemical
      staining of these cells also failed to demonstrate expression of wild-type VP2,
      indicating that the lack of expression was at the RNA level and the VP2 protein
      was not toxic to CEFs. Chickens vaccinated with a DNA vaccine consisting of the
      bicistronic vector containing the codon-optimized VP2 elicited a humoral immune
      response as measured by a VP2-specific ELISA. This VP2 codon-optimized
      bicistronic cassette was rescued into the MeHV-1 genome generating a vectored
      vaccine against ChPV disease. 

PMID- 23861019
TI  - Is There a Role for Menopausal Hormone Therapy (MHT) for Cardiovascular Disease
      Prevention in Select Postmenopausal Women?
AB  - OPINION STATEMENT: Although the US Preventive Services Task Force and other
      contemporary guidelines recommend that Menopausal Hormone Therapy (MHT) not be
      used for prevention of chronic conditions, its use for prevention of
      cardiovascular disease remains controversial. The Women's Health Initiative and
      the Heart and Estrogen/progestin Replacement Study explored the benefits and
      risks of MHT for cardiovascular disease, primary and secondary prevention
      respectively, but challenges to these data include suboptimal hormone therapy
      adherence and the advanced age of the women at initiation of MHT. Here we discuss
      the recent literature impacting MHT management of the peri- and post-menopausal
      women who are concerned about cardiovascular disease risk.

PMID- 23861020
TI  - Cardiac magnetic resonance-derived right ventricular outflow tract systolic flow
      acceleration: a novel index of right ventricular function and prognosis in
      patients with pulmonary arterial hypertension.
AB  - To validate the right ventricular outflow tract systolic flow acceleration
      (RVOTACC; peak flow velocity/time-to-peak velocity) measured by phase-contrast
      (PC)-cardiovascular magnetic resonance (CMR) as a novel index of right
      ventricular (RV) function, and to investigate its clinical implications in
      patients with pulmonary arterial hypertension (PAH). Thirty (38% male, 43 +/- 15
      years old) out of 55 consecutive patients who were initially diagnosed with PAH
      at the referral center were prospectively enrolled between March 2009 and July
      2010 and were followed for PAH-related cardiovascular events for 2 years. The
      invasively measured maximum dP/dt (dP/dtmax) was used as an index of RV
      contractility. The PC-CMR-derived RVOTACC was compared with well-known prognostic
      parameters. The PC-CMR-derived RVOTACC correlated strongly with the dP/dtmax and
      estimated RV function more accurately than the CMR-derived RV ejection fraction.
      The CMR-derived RVOTACC level (HR = 0.87, 95% CI 0.78-0.98, p = 0.038) could be
      another powerful prognostic index compared with the functional capacity (hazard
      ratio [HR] = 0.88, 95% confidence interval [CI] 0.78-0.97, p = 0.035) and REVEAL
      Registry risk score (HR = 0.83, CI 0.56-0.95, p = 0.012). Furthermore, receiver
      operating characteristic analysis identified >=0.4 m/s2 as the optimal RVOTACC
      cut-off for predicting subsequent cardiovascular events. PC-CMR-derived RVOTACC
      is a promising non-invasively measured index of RV function and prognosis in
      patients with PAH.

PMID- 23861021
TI  - Rapidly constructed scaffold-free embryonic stem cell sheets for ocular surface
      reconstruction.
AB  - This study is an extension of our previously published work demonstrating the
      generation of corneal epithelial sheets using optimal centrifugation procedure.
      In this study, we investigated the therapeutic potential of embryonic stem cells
      (ESCs) for ocular surface reconstruction in rabbits with limbal stem cell
      deficiency (LSCD) using the centrifugation method. Rabbits with LSCD were
      assigned to two groups: 30 LSCD rabbits were treated with scaffold-free embryonic
      stem cells sheets (SESCS) and six LSCD rabbits received no treatment (control
      group). The two groups were followed up for 15 days using slit lamp observation.
      Cytokeratin K3, mucin 5AC, and OCT-4 were used to evaluate the re
      epithelialization of the cornea. Fluorescent DiIC18(3)-DS dye was used to trace
      the transplanted cells. Atomic force microscopy (AFM) was used to investigate the
      cultured epithelial cells of the SESCS-treated group. The SESCS transplant
      facilitated the reconstruction of the ocular surface in 75% of the treated
      animals. Conjunctivalization and neovascularization were observed in the control
      group. The SESCS group was K3 positive and MUC5AC negative, and OCT-4 was
      observed on the re-epithelialized corneal epithelium. Labeled SESCS cells were
      detected in vivo at 15 days post-transplant. Using AFM, three different types of
      cultured cells were identified in the rabbit corneal epithelium of the SESCS
      treatment group. The SESCS were demonstrated to reconstruct the ocular surface in
      rabbits with LSCD. ES cells differentiated into corneal epithelial cells when in
      direct contact with the stroma and thus can serve as a cell source in corneal
      tissue engineering.

PMID- 23861018
TI  - The genetic and antigenic diversity of avian influenza viruses isolated from
      domestic ducks, muscovy ducks, and chickens in northern and southern Vietnam,
      2010-2012.
AB  - To estimate the prevalence of avian influenza virus infection in Vietnam,
      surveillance was conducted in domestic and wild birds from households, live-bird
      markets, slaughtering sites, and bird sanctuaries in Vietnam between October 2010
      and October 2012. Of the 4,550 samples collected, 226 influenza A virus isolates
      were obtained from domestic ducks, muscovy ducks, and chickens. Of these, 25 and
      22 H5N1 highly pathogenic avian influenza viruses (HPAIVs) were isolated from
      apparently healthy domestic ducks in live-bird markets and slaughtering sites in
      northern and southern Vietnam, respectively. The HA genes of H5 viruses isolated
      from birds in northern Vietnam phylogenetically belonged to the genetic clade
      2.3.2.1 and those in southern Vietnam belonged to the genetic clade 1.1. In
      addition, 39 H3, 12 H4, 1 H5, 93 H6, 2 H7, 18 H9, 3 H10, and 11 H11 viruses were
      isolated. Phylogenetic and antigenic analyses of the H6 and H9 viruses revealed
      that they were closely related to the isolates obtained from domestic poultry in
      China. Phylogenetic analyses of internal gene segments of these isolates revealed
      that these viruses were circulating in both domestic and wild birds in Asia and
      reassortment events had occurred frequently. Therefore, it will be important to
      continue the surveillance and strict controls over the movement and trade of
      poultry and poultry products in order to eradicate H5N1 HPAIV from Asia. 

PMID- 23861022
TI  - Quantification of swelling and erosion in the controlled release of a poorly
      water-soluble drug using synchrotron X-ray computed microtomography.
AB  - The hydration layer plays a key role in the controlled drug release of gel
      forming matrix tablets. For poorly water-soluble drugs, matrix erosion is
      considered as the rate limiting step for drug release. However, few
      investigations have reported on the quantification of the relative importance of
      swelling and erosion in the release of poorly soluble drugs, and three
      dimensional (3D) structures of the hydration layer are poorly understood. Here,
      we employed synchrotron radiation X-ray computed microtomography with 9-MUm
      resolution to investigate the hydration dynamics and to quantify the relative
      importance of swelling and erosion on felodipine release by a statistical model.
      The 3D structures of the hydration layer were revealed by the reconstructed 3D
      rendering of tablets. Twenty-three structural parameters related to the volume,
      the surface area (SA), and the specific surface area (SSA) for the hydration
      layer and the tablet core were calculated. Three dominating parameters, including
      SA and SSA of the hydration layer (SA hydration layer and SSA hydration layer )
      and SA of the glassy core (SA glassy core ), were identified to establish the
      statistical model. The significance order of independent variables was SA
      hydration layer > SSA hydration layer > SA glassy core , which quantitatively
      indicated that the release of felodipine was dominated by a combination of
      erosion and swelling. The 3D reconstruction and structural parameter calculation
      methods in our study, which are not available from conventional methods, are
      efficient tools to quantify the relative importance of swelling and erosion in
      the controlled release of poorly soluble drugs from a structural point of view. 

PMID- 23861023
TI  - The Xer/dif site-specific recombination system of Campylobacter jejuni.
AB  - Chromosome dimers, which form during the bacterial life cycle, represent a
      problem that must be solved by the bacterial cell machinery so that chromosome
      segregation can occur effectively. The Xer/dif site-specific recombination
      system, utilized by most bacteria, resolves chromosome dimers into monomers using
      two tyrosine recombinases, XerC and XerD, to perform the recombination reaction
      at the dif site which consists of 28-30 bp. However, single Xer recombinase
      systems have been recently discovered in several bacterial species. In
      Streptococci and Lactococci a single recombinase, XerS, is capable of completing
      the monomerisation reaction by acting at an atypical dif site called dif SL (31
      bp). It was recently shown that a subgroup of epsilon-proteobacteria including
      Campylobacter spp. and Helicobacter spp. had a phylogenetically distinct Xer/dif
      recombination system with only one recombinase (XerH) and an atypical dif motif
      (difH). In order to biochemically characterize this system in greater detail,
      Campylobacter jejuni XerH was purified and its DNA-binding activity was
      characterized. The protein showed specific binding to the complete difH site and
      to both halves separately. It was also shown to form covalent complexes with difH
      suicide substrates. In addition, XerH was able to catalyse recombination between
      two difH sites located on a plasmid in Escherichia coli in vivo. This indicates
      that this XerH protein performs a similar function as the related XerS protein,
      but shows significantly different binding characteristics. 

PMID- 23861024
TI  - Gene replacement therapy for retinal CNG channelopathies.
AB  - Visual phototransduction relies on the function of cyclic nucleotide-gated
      channels in the rod and cone photoreceptor outer segment plasma membranes. The
      role of these ion channels is to translate light-triggered changes in the second
      messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal
      that is further processed within the retinal network and then sent to higher
      visual centers. Rod and cone photoreceptors express distinct CNG channels. The
      rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits,
      whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits.
      Mutations in any of these channel subunits result in severe and currently
      untreatable retinal degenerative diseases like retinitis pigmentosa or
      achromatopsia. In this review, we provide an overview of the human diseases and
      relevant animal models of CNG channelopathies. Furthermore, we summarize recent
      results from preclinical gene therapy studies using adeno-associated viral
      vectors and discuss the efficacy and translational potential of these gene
      therapeutic approaches. 

PMID- 23861026
TI  - Factors that determine body composition of female systemic lupus erythematosus
      (SLE) patients in Sri Lanka: a comparative study using dual-energy x-ray
      absorptiometry.
AB  - Studies on body composition and its determinants among SLE patients are limited.
      Estimation of body composition, analysis of determinants and associations of
      different body compartments are important in planning long-term care of these
      patients. The aim of the study was to identify the changes in body composition
      among SLE patients and assess the effect of corticosteroid use, patient and
      disease-related variables on body composition. We compared lean mass, fat mass,
      bone mineral density (BMD), and bone mineral content (BMC) determined by dual
      energy x-ray absorptiometry technology, in a group of premenopausal women with
      SLE (n = 27) and an age-matched healthy group of women (n = 27). The median (IQR)
      duration of SLE was 3 (2-5) years while median (IQR) duration and dose of
      prednisolone therapy were 108 (88 - 172) weeks and 9730 (6160-15360) mg,
      respectively. No significant difference was observed in body mass index (BMI) or
      total fat mass between the two groups. SLE patients, however, had significantly
      lower lean mass (p < 0.001), BMD (p < 0.001) and BMC (p < 0.005) than healthy
      controls. Among cases, compared with lean mass, total body fat content showed
      stronger associations with total body BMD (r = 0.49, p < 0.01) and total body BMC
      (r = 0.63, p < 0.01). When a stepwise regression model was fitted, lean mass
      among controls and total fat mass among cases emerged as the best predictors of
      BMC/BMD. No significant correlations were found between the disease duration or
      cumulative glucocorticosteroid dose and total body BMD, total body BMC, lean mass
      or total fat content in SLE patients. 

PMID- 23861025
TI  - Group 1 LEA proteins, an ancestral plant protein group, are also present in other
      eukaryotes, and in the archeae and bacteria domains.
AB  - Water is an essential element for living organisms, such that various responses
      have evolved to withstand water deficit in all living species. The study of these
      responses in plants has had particular relevance given the negative impact of
      water scarcity on agriculture. Among the molecules highly associated with plant
      responses to water limitation are the so-called late embryogenesis abundant (LEA)
      proteins. These proteins are ubiquitous in the plant kingdom and accumulate
      during the late phase of embryogenesis and in vegetative tissues in response to
      water deficit. To know about the evolution of these proteins, we have studied the
      distribution of group 1 LEA proteins, a set that has also been found beyond the
      plant kingdom, in Bacillus subtilis and Artemia franciscana. Here, we report the
      presence of group 1 LEA proteins in green algae (Chlorophyita and Streptophyta),
      suggesting that these group of proteins emerged before plant land colonization.
      By sequence analysis of public genomic databases, we also show that 34 prokaryote
      genomes encode group 1 LEA-like proteins; two of them belong to Archaea domain
      and 32 to bacterial phyla. Most of these microbes live in soil-associated
      habitats suggesting horizontal transfer from plants to bacteria; however, our
      phylogenetic analysis points to convergent evolution. Furthermore, we present
      data showing that bacterial group 1 LEA proteins are able to prevent enzyme
      inactivation upon freeze-thaw treatments in vitro, suggesting that they have
      analogous functions to plant LEA proteins. Overall, data in this work indicate
      that LEA1 proteins' properties might be relevant to cope with water deficit in
      different organisms. 

PMID- 23861027
TI  - A Japanese pediatric patient with coexisting systemic lupus erythematosus and
      familial Mediterranean fever.
AB  - This case report describes a Japanese girl with systemic lupus erythematosus who
      had recurrent fevers and erythema nodosum. She was later found to carry the
      complex allele E148Q/R202Q/P369S/R408Q of MEFV, the gene responsible for familial
      Mediterranean fever.

PMID- 23861028
TI  - Overexpression of methyl-CpG-binding protein 2 and autoimmunity: evidence from
      MECP2 duplication syndrome, lupus, MECP2 transgenic and Mecp2 deficient mice.

PMID- 23861030
TI  - ZincExplorer: an accurate hybrid method to improve the prediction of zinc-binding
      sites from protein sequences.
AB  - As one of the most important trace elements within an organism, zinc has been
      shown to be involved in numerous biological processes and closely implicated in
      various diseases. The zinc ion is important for proteins to perform their
      functional roles. To provide in-depth functional annotation of zinc-binding
      proteins, an initial but crucial step is the accurate recognition of zinc-binding
      sites. Motivated by the biological importance of zinc, we propose a new method
      called ZincExplorer to predict zinc-binding sites from protein sequences.
      ZincExplorer is a hybrid method that can accurately predict zinc-binding sites
      from protein sequences. It integrates the outputs of three different types of
      predictors, namely, SVM-, cluster- and template-based predictors. Four types of
      zinc-binding amino acids CHEDs (i.e. CYS, HIS, ASP and GLU) could be predicted
      using ZincExplorer. It achieved a high AURPC (Area Under Recall-Precision Curve)
      of 0.851, and a precision of 85.6% (specificity = 98.4%, MCC = 0.747) at the
      70.0% recall for the CHEDs on the 5-fold cross-validation test. When tested on an
      independent dataset containing 2023 zinc-binding CHEDs and 14,493 non-zinc
      binding CHEDs, it achieved about 3-8% higher AURPC in comparison to two other
      sequence-based predictors. Moreover, ZincExplorer could also identify the
      interdependent relationships (IRs) of the predicted zinc-binding sites bound to
      the same zinc ion, which makes it a useful tool for providing in-depth zinc
      binding site annotation.

PMID- 23861029
TI  - Invasive fungal infections in Argentine patients with systemic lupus
      erythematosus.
AB  - INTRODUCTION: Infections are the leading cause of morbidity and mortality in
      patients with systemic lupus erythematosus (SLE). Invasive fungal infections
      (IFI) comprise a group of diseases caused by Cryptococcus, Histoplasma,
      Aspergillus and Candida. Few studies of IFI have been published in patients with
      SLE and associated factors have not been completely defined. OBJECTIVES: The
      objectives of this paper are to estimate the frequency of IFI in admitted
      patients with SLE in our hospital, to determine the risk factors associated with
      IFI in our patients with SLE, and to compare IFI group with a control group (SLE
      without IFI). METHODS: The medical charts of patients with IFI (EORTC/MSG, 2008)
      and SLE (ACR, 1997) admitted to our hospital from June 2001 until June 2012 were
      reviewed. To identify factors associated with IFI, we developed a case-control
      study (SLE + IFI vs SLE alone) in a one to three ratio adjusted for sex and age
      and hospitalization for other reasons. Comparison was made of demographic
      characteristics, duration of disease and disease activity previous to IFI
      diagnosis, especially three months before fungal infection. We defined severe
      activity as SLEDAI >= 8. Infection by fungi of the genus Candida was considered
      only in its disseminated form. RESULTS: Ten cases of IFI were identified in 208
      patients with SLE admitted between June 2001 and June 2012. We included 40
      patients with SLE (10 with IFI and 30 controls). Of the SLE-IFI patients, eight
      were women and the average age was 27.5 years (range, 19-42 years). Fungal
      isolation: eight Cryptococcus neoformans, one Histoplasma capsulatum and one
      Candida albicans. Sites affected: five in peripheral blood, five in central
      nervous system (CNS), four in skin/soft tissue and one in pleura. Mortality was
      40% (p = 0.002), with Cryptococcus neoformans being the most common fungus. The
      SLE disease activity was severe in 70% of infected patients and no significant
      difference with the control group was found (p = 0.195). We also found no
      association with leukopenia, lymphopenia, hypocomplementemia,
      hypogammaglobulinemia or anti-DNA positivity; neither with meprednisone doses >20
      mg/day or intravenous methylprednisolone pulse therapy before fungal infection.
      The use of immunosuppressive therapy with azathioprine showed a significant
      association (p = 0.017). Cyclophosphamide (p = 0.100) or mycophenolate mofetil (p
      = 0.256) did not show similar results. CONCLUSION: The frequency of IFI in
      hospitalized SLE patients in our hospital was 4.8%. Cryptococcus neoformans was
      the most common etiologic agent and was primarily responsible for the deaths in
      this cohort. These data are consistent with publications in East Asia rather than
      North America where Candida spp. is more common. Unlike other publications,
      previous immunosuppression with azathioprine was the only risk factor associated
      with the development of the infection. Invasive fungal infection should be
      suspected in hospitalized patients with SLE and immunosuppression with CNS or
      atypical cutaneous manifestation of SLE in order to start appropriate treatment
      early and obtain better outcome.

PMID- 23861031
TI  - Behind bullying and defending: same-sex and other-sex relations and their
      associations with acceptance and rejection.
AB  - Relatively little is known about bullying and defending behaviors of children in
      early elementary school. However, this period is crucial for children's
      development as at this age they start to participate in a stable peer group, and
      difficulties in social interactions can be detected early by professionals. An
      interactive animated web-based computer program was used in this study to assess
      peer relationships among young children. The computerized assessment was
      conducted among 2,135 children in grades 1-2 from 22 elementary schools to
      examine the association of bullying, victimization, and defending with being
      accepted or rejected. Same-sex and other-sex peer relations were distinguished
      using dyadic data. Both boys and girls were more likely to accept same-sex
      classmates than other-sex classmates, and boys were more often nominated than
      girls as perpetrators of bullying against both boys and girls. It was found that
      bullies were rejected by those for whom they posed a potential threat, and that
      defenders were preferred by those classmates for whom they were a potential
      source of protection. Bullies chose victims who were rejected by significant
      others, but contrary to expectations, children who bullied boys scored low on
      peer affection. It is possible that these bullies were not strategic enough to
      select the "right" targets. Overall, the current findings provide evidence for
      strategies involved in bullying and defending at early age.

PMID- 23861032
TI  - Primary prevention for resettled refugees from Burma: where to begin?
AB  - Developing effective primary prevention initiatives may help recently arrived
      refugees retain some of their own healthy cultural habits and reduce the tendency
      to adopt detrimental ones. This research explores recent arrivals' knowledge
      regarding eating behaviors, physical activity and sleep habits. Working
      collaboratively with community members, a healthy living curriculum was adapted
      and pilot tested in focus groups. A community-engaged approach to revising and
      implementing a health promotion tool was effective in beginning dialogue about
      primary prevention among a group of recently arrived refugees from Burma. Seven
      themes were identified as particularly relevant: food choices, living
      environment, health information, financial stress, mobility/transportation,
      social interaction and recreation, and hopes and dreams. Refugees desire more
      specific information about nutrition and exercise, and they find community health
      workers an effective medium for delivering this information. The outcomes of this
      study may inform future targeted interventions for health promotion with refugees
      from Burma. 

PMID- 23861033
TI  - Local smoke-free policy experiences in Appalachian communities.
AB  - In Appalachian areas, strong tobacco control policies are not in place, so
      residents are not adequately protected from secondhand smoke exposure. This area
      is predominantly rural, and residents experience a high burden of tobacco-related
      illnesses. There has been limited examination of elements that hinder smoke-free
      policy adoption in these vulnerable communities. Key informant interviews were
      conducted with individuals identified as being knowledgeable about local tobacco
      control policy activities within a random selection of Appalachian communities
      within 6 states with (n = 15) and without (n = 12) local smoke-free policies.
      Five key themes emerged from the qualitative interviews: (1) opposition to
      tobacco control, (2) need for local involvement, (3) role of community
      coalitions, (4) leveraging outside advocates, and (5) working with decision
      makers. In Appalachian communities, the local context and locally-based
      coalitions were critical to promote the adoption of smoke-free policies. 

PMID- 23861034
TI  - Prevalence of hepatitis A antibodies in Eastern Bolivia: a population-based
      study.
AB  - The seroprevalence of hepatitis A virus (HAV) is changing from high to
      intermediate endemicity in several Latin American countries, but the pattern in
      the Andean Latin American countries is unknown. A seroepidemiological survey (n =
      436) of HAV in schoolchildren living in the Cochabamba region of Bolivia was
      conducted in 2010. A questionnaire was completed by parents to obtain
      demographic, socio-economic, and housing data, and blood samples were collected.
      The overall prevalence of HAV IgG was 95.4% (95% CI 93.5-97.4). The prevalence
      was higher in children aged 5-10 years (97%) and pre-adolescents aged 10-13 years
      (97.9%). The prevalence was also higher in subjects whose parents had a low level
      of education (99.4-99.5%), who lived in rural areas (98.7%), lived in
      municipalities with low urban development (99.1-100%), had water delivered at
      home from a tanker (99.4%), and spoke Quechua at home (99.5%). The descriptive
      and bivariate analysis suggested that no change in HAV epidemiology has occurred
      in Cochabamba.

PMID- 23861035
TI  - Interventions for implementation of thromboprophylaxis in hospitalized medical
      and surgical patients at risk for venous thromboembolism.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a leading cause of morbidity and
      mortality in hospitalized patients. Numerous randomized controlled trials (RCTs)
      show that using thromboprophylaxis in hospitalized patients at risk for VTE is
      safe, effective and cost-effective. Despite this, prophylactic therapies for VTE
      are underutilized. System-wide interventions may be more effective to improve the
      use of VTE prophylaxis than relying on individual providers' prescribing
      behaviors. OBJECTIVES: To assess the effects of interventions designed to
      increase the implementation of thromboprophylaxis in hospitalized adult medical
      and surgical patients at risk for venous thromboembolism (VTE), assessed in terms
      of: 1. Increase in the proportion of patients who receive prophylaxis and
      appropriate prophylaxis 2. Reduction in risk of symptomatic VTE3. Reduction in
      risk of asymptomatic VTE4. Safety of the intervention. SEARCH METHODS: The
      Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC)
      searched the Group's Specialised Register (last searched July 2010) and the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library)
      2010, Issue 3. We searched the PubMed, EMBASE, and SCOPUS databases (19 April
      2010) as well as the reference lists of relevant review articles. SELECTION
      CRITERIA: We included all studies whose interventions aimed to increase the use
      of prophylaxis and/or appropriate prophylaxis, decrease the proportion of
      symptomatic VTE, or decrease the proportion of asymptomatic VTE in hospitalized
      adult patients. We excluded studies that simply distributed published guidelines
      and studies whose interventions were not clearly described. DATA COLLECTION AND
      ANALYSIS: We collected the following outcomes: the proportion of patients who
      received prophylaxis (RP), the proportion of patients who received appropriate
      prophylaxis (RAP) (primary outcomes), and the occurrence of symptomatic VTE,
      asymptomatic VTE, and safety outcomes such as bleeding. We categorized
      interventions into education, alerts, and multifaceted interventions. We meta
      analyzed RCTs and non-randomized studies (NRS) separately by random effects meta
      analysis, and assessed heterogeneity using the I(2)statistic and subgroup
      analyses. Before analysis, we decided that results would be pooled if three or
      more studies were available for a particular intervention. We assessed
      publication bias using funnel plots and cumulative meta-analysis. MAIN RESULTS:
      We included a total of 55 studies. One of these reported data in patient-days and
      could not be quantitatively analyzed with the others. The 54 remaining studies (8
      RCTs and 46 NRS) eligible for inclusion in our quantitative synthesis enrolled a
      total of 78,343 participants. Among RCTs, there were sufficient data to pool
      results for one primary outcome (received prophylaxis) for the 'alert'
      intervention. Alerts, such as computerized reminders or stickers on patients'
      charts, were associated with a risk difference (RD) of 13%, signifying an
      increase in the proportion of patients who received prophylaxis (95% confidence
      interval (CI) 1% to 25%). Among NRS, there were sufficient data to pool both
      primary outcomes for each intervention type. Pooled risk differences for received
      prophylaxis ranged from 8% to 17%, and for received appropriate prophylaxis
      ranged from 11% to 19%. Education and alerts were associated with statistically
      significant increases in prescription of appropriate prophylaxis, and
      multifaceted interventions were associated with statistically significant
      increases in prescription of any prophylaxis and appropriate prophylaxis.
      Multifaceted interventions had the largest pooled effects. I(2) results showed
      substantial statistical heterogeneity which was in part explained by patient
      types and type of hospital. A subgroup analysis showed that multifaceted
      interventions which included an alert may be more effective at improving rates of
      prophylaxis and appropriate prophylaxis than those without an alert. Results for
      VTE and safety outcomes did not show substantial benefits or harms, although most
      studies were underpowered to assess these outcomes. AUTHORS' CONCLUSIONS: We
      reviewed a large number of studies which implemented a variety of system-wide
      strategies aimed to improve thromboprophylaxis rates in many settings and patient
      populations. We found statistically significant improvements in prescription of
      prophylaxis associated with alerts (RCTs) and multifaceted interventions (RCTs
      and NRS), and improvements in prescription of appropriate prophylaxis in NRS with
      the use of education, alerts and multifaceted interventions. Multifaceted
      interventions with an alert component may be the most effective. Demonstrated
      sources of heterogeneity included patient types and type of hospital. The results
      of our review will help physicians, nurses, pharmacists, hospital administrators
      and policy makers make practical decisions about local adoption of specific
      system-wide measures to improve prevention of VTE, an important public health
      issue. We did not find a significant benefit for VTE outcomes; however, earlier
      RCTs assessing the efficacy of thromboprophylaxis which were powered to address
      these outcomes have demonstrated the benefit of prophylactic therapies and a
      favourable balance of benefits versus the increased risk of bleeding events.

PMID- 23861036
TI  - B-cell receptor configuration and mutational analysis of patients with chronic
      lymphocytic leukaemia and trisomy 12 reveal recurrent molecular abnormalities.
AB  - Trisomy 12 (+12) is the third most frequent cytogenetic aberration in chronic
      lymphocytic leukaemia (CLL) retrievable both as the sole chromosomal abnormality
      or in association with additional alterations. NOTCH1 mutations are known to be
      more prevalent among +12 patients, whereas mutations of FBXW7, a gene involved in
      NOTCH1 degradation, that lead to the constitutional activation of NOTCH1 have not
      been investigated in this setting. We analyzed a unicentric cohort of 44 +12
      patients with CLL for mutations of TP53, NOTCH1 and FBXW7 genes, and we
      correlated them with B-cell receptor (BCR) configurations. FBXW7, TP53 and NOTCH1
      mutations were identified in 4.5%, 6.8% and 18.2% of patients, respectively.
      FBXW7 and NOTCH1 mutations appeared in a mutually exclusive fashion, suggesting
      that both aberrations might affect the same biological pathway. We found that
      44.1% of +12 CLL patients had stereotyped B-cell receptors, which is
      significantly higher than that observed in patients with CLL and no +12 (27%, p =
      0.01). Subsets #1, #8, #10, #28 and #59 were the most represented stereotyped
      patterns, and IGHV4-39*01 was the gene configuration most commonly used. There
      was a significantly higher risk for Richter's syndrome (RS) transformation in
      patients with NOTCH1 or FBXW7 mutations, with four of the seven (57%) patients
      developing RS and characterized at least by one of the two abnormalities. These
      observations suggest that, similarly to the aberrations of NOTCH1, FBXW7 gene
      mutations may also result in cell proliferation and evasion from apoptosis in
      patients with +12 CLL. Together with the extremely high frequency of stereotyped
      BCRs and RS transformation, these abnormalities appear to cluster in these CLL
      patients with additional chromosome 12, suggesting a connection with the
      prognosis of the disease.

PMID- 23861037
TI  - Long-term prognosis and risk factors among patients with HPV-associated
      oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: A subset of patients with human papillomavirus (HPV)-associated
      oropharyngeal squamous cell carcinoma (HPV-OSCC) experience poor clinical
      outcomes. The authors of this report explored prognostic risk factors for overall
      survival (OS) and recurrence-free survival (RFS). METHODS: Patients with incident
      HPV-OSCC who received treatment at the Johns Hopkins Hospital between 1997 and
      2008 and who had tissue available for HPV testing as well as demographic and
      clinicopathologic information (N = 176) were included. Tissue was tested for HPV
      by in situ hybridization (ISH) and/or p16 immunohistochemistry. Demographic and
      clinicopathologic information was extracted from medical records. RESULTS: In
      total, 157 of 176 patients (90%) with OSCC had HPV-associated disease (HPV-OSCC).
      In the patients with HPV-OSCC, the 3-year and 5-year OS rates were 93% (95%
      confidence interval [CI], 88%-98%) and 89% (95% CI, 81%-97%), respectively.
      Shorter survival was observed among older patients (hazard ratio [HR], 2.33 per
      10-year increase; 95% CI, 1.05-5.16 per 10-year increase; P = .038), patients
      with advanced clinical T classification (HR, 5.78; 95% CI, 1.60-20.8; P = .007),
      and patients who were currently using tobacco (HR, 4.38; 95% CI, 1.07-18.0; P =
      .04). Disease recurrence was associated with advanced clinical T-classification
      (HR, 8.32; 95% CI, 3.06-23; P < .0001), current/former alcohol use (HR, 13; 95%
      CI, 1.33-120; P = .03), and unmarried status (HR, 3.28; 95% CI, 1.20-9.00; P =
      .02). Patients who remained recurrence free for 5 years had an 8.6% chance of
      recurrence by 10 years (1-sided 95% CI upper bound, 19%; P = .088). CONCLUSIONS:
      In this study, prognostic risk factors were identified for patients with HPV
      OSCC. The observed recurrence rates between 5 years and 10 years after definitive
      therapy need to be validated in additional studies to determine whether extended
      cancer surveillance is warranted in this cancer population. Cancer 2013;119:3462
      3471.. (c) 2013 American Cancer Society.

PMID- 23861038
TI  - Diversity and symbiotic effectiveness of beta-rhizobia isolated from sub-tropical
      legumes of a Brazilian Araucaria Forest.
AB  - While the occurrence of Betaproteobacteria occupying the nodules of tropical
      legumes has been shown, little is known about subtropical areas. Araucaria Forest
      is a subtropical endangered ecosystem, and a better understanding of the legume
      rhizobial symbionts may allow their use in land reclamation. The 16S rRNA gene of
      bacteria isolated from nine leguminous species was sequenced and their nodulation
      tested in Mimosa scabrella and Phaseolus vulgaris. 196 isolates were identified
      as eight genotypes: Pantoea, Pseudomonas, Bradyrhizobium sp1-2, Rhizobium, and
      Burkholderia sp1-3. The majority of the isolates from native plants (87 %) were
      taxonomically related to beta-rhizobia, namely Burkholderia, however the legumes
      Galactia crassifolia and Collea speciosa were nodulated by both alpha and beta
      rhizobia, and Acacia dealbata, an exotic plant, only by alpha-rhizobia. The nifH
      genes of some isolates were sequenced and N-fixing potential shown by the
      acetylene reduction test. Most of the isolates nodulated the test plants, some
      were effective in M. scabrella, but all presented low efficiency in the exotic
      promiscuous legume P. vulgaris. Pantoea and Pseudomonas did not nodulate and
      probably are endophytic bacteria. The presented data shows diversity of alpha,
      beta and gamma-Proteobacteria in nodules of subtropical legumes, and suggests
      host specificity with beta-rhizobia. Potential isolates were found for M.
      scabrella, indicating that a high N-fixing strain may be further inoculated in
      plants for use in reforestation. 

PMID- 23861039
TI  - Responses of antioxidant defenses and membrane damage to drought stress in fruit
      bodies of Auricularia auricula-judae.
AB  - Fruit bodies of Auricularia auricula-judae are often subjected to drought stress
      and became dormant. The responses of antioxidant defenses and membrane damage to
      drought stress were investigated in this study. Picked fruit bodies were exposed
      to sunlight and dehydrated naturally and samples were collected at different
      levels of water loss (0, 10, 30, 50, and 70%) for determination of electrolyte
      leakage (EL); contents of malondialdehyde (MDA), ascorbic acid (AsA) and reduced
      glutathione (GSH); and activities of superoxide dismutase (SOD), catalase (CAT)
      and peroxidase (POD). Results showed that membrane permeability (assessed by EL)
      and membrane lipid peroxidation (MDA content) remained unchanged at all levels of
      water loss studied. Contents of AsA and GSH showed no change at 0, 10 and 30% of
      water loss, however, both of them increased significantly at 50 and 70% of water
      loss. SOD activity significantly increased with the rising of water loss from 0
      to 30%, reached the peak at 30 and 50% of water loss, and then significantly
      decreased at 70% of water loss. A gradual increase in POD and CAT activities was
      observed when water loss rose from 0 to 50%. As water loss went up to 70%, POD
      activity remained the same as that at 50%, but CAT activity decreased. The
      results indicate that the increased activities of enzymatic antioxidants (SOD,
      CAT and POD) and contents of non-enzymatic antioxidants (AsA and GSH) in fruit
      bodies of A. auricula-judae can effectively scavenge reactive oxygen species,
      cause no damage to cell membranes as demonstrated by the unchanged EL and MDA
      content, and contribute to dormancy under drought stress.

PMID- 23861040
TI  - Induction of laccases in Trametes versicolor by aqueous wood extracts.
AB  - The induction of laccase isoforms in Trametes versicolor HEMIM-9 by aqueous
      extracts (AE) from softwood and hardwood was studied. Samples of sawdust of Pinus
      sp., Cedrela sp., and Quercus sp. were boiled in water to obtain AE. Different
      volumes of each AE were added to fungal cultures to determine the amount of AE
      needed for the induction experiments. Laccase activity was assayed every 24 h for
      15 days. The addition of each AE (50 to 150 MUl) to the fungal cultures increased
      laccase production compared to the control (0.42 +/- 0.01 U ml(-1)). The highest
      laccase activities detected were 1.92 +/- 0.15 U ml(-1) (pine), 1.87 +/- 0.26 U
      ml(-1) (cedar), and 1.56 +/- 0.34 U ml(-1) (oak); laccase productivities were
      also significantly increased. Larger volumes of any AE inhibited mycelial growth.
      Electrophoretic analysis revealed two laccase bands (lcc1 and lcc2) for all the
      treatments. However, when lcc2 was analyzed by isoelectric focusing, inducer
      dependent isoform patterns composed of three (pine AE), four (oak AE), and six
      laccase bands (cedar AE) were observed. Thus, AE from softwood and hardwood had
      induction effects in T. versicolor HEMIM-9, as indicated by the increase in
      laccase activity and different isoform patterns. All of the enzymatic extracts
      were able to decolorize the dye Orange II. Dye decolorization was mainly
      influenced by pH. The optimum pH for decolorization was pH 5 (85%), followed by
      pH 7 (50%) and pH 3 (15%). No significant differences in the dye decolorizing
      capacity were detected between the control and the differentially induced laccase
      extracts (oak, pine and cedar). This could be due to the catalytic activities of
      isoforms with pI 5.4 and 5.8, which were detected under all induction conditions.

PMID- 23861041
TI  - Temperature influences beta-carotene production in recombinant Saccharomyces
      cerevisiae expressing carotenogenic genes from Phaffia rhodozyma.
AB  - Red yeast Phaffia rhodozyma is a prominent microorganism able to synthesize
      carotenoid. Here, three carotenogenic cDNAs of P. rhodozyma CGMCC 2.1557, crtE,
      crtYB and crtI, were cloned and introduced into Saccharomyces cerevisiae INVSc1.
      The recombinant Sc-EYBI cells could synthesize 258.8 +/- 43.8 MUg g(-1) dry cell
      weight (DCW) of beta-carotene when growing at 20  degrees C, about 59-fold higher
      than in those growing at 30  degrees C. Additional expression of the catalytic
      domain of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from S. cerevisiae (Sc
      EYBIH) increased the beta-carotene level to 528.8 +/- 13.3 MUg g(-1) DCW as cells
      growing at 20  degrees C, 27-fold higher than cells growing at 30  degrees C,
      although cells grew faster at 30  degrees C than at 20  degrees C. Consistent
      with the much higher beta-carotene level in cells growing at 20  degrees C,
      transcription level of three crt genes and cHMG1 gene in cells growing at 20 
      degrees C was a little higher than in those growing at 30  degrees C. Meanwhile,
      expression of three carotenogenic genes and accumulation of beta-carotene
      promoted cell growth. These results reveal the influence of temperature on beta
      carotene biosynthesis and may be helpful for improving beta-carotene production
      in recombinant S. cerevisiae.

PMID- 23861043
TI  - Effects of different influent C/N ratios on the performance of various earthworm
      eco-filter systems: nutrient removal and greenhouse gas emission.
AB  - In this study, we sought to identify influent carbon-to-nitrogen (C/N) ratios
      that yield relatively high nutrient removal efficiency with relatively low
      greenhouse gas (GHG) emissions. The earthworm eco-filter (EE) system, which is
      composed of earthworms and plants (EP group), was found to be optimal for
      maximizing nutrient removal while reducing GHG emissions. In this EE system, the
      optimal influent C/N ratio for nutrient removal and GHG emission under C2N
      treatment conditions. Nutrient removal efficiency under this condition was 85.19
      +/- 6.40% chemical oxygen demand, 71.99 +/- 11.28% total nitrogen, and 77.91 +/-
      8.51% total phosphorus, while the CO2 emission rate was 678.89 +/- 201.87 mg m(
      2) h(-1). Moreover, the highest nutrient removal and GHG emission rates were both
      achieved in late summer (August). Thus, carbon variation, season, system
      variation, as well as synergistic interaction between system variations and
      seasons, significantly affect nutrient removal efficiencies and GHG emissions.

PMID- 23861042
TI  - Investigation on the mechanisms for biotransformation of saponins to diosgenin.
AB  - In order to improve the efficiency of biotransformation of saponins in Dioscorea
      zingiberensis to diosgenin, a new enzymatic model was developed to investigate
      the mechanism of the metabolic systems. Four main saponin hydrolases (E1, E2, E3
      and E4) were purified from Trichoderma reesei. Using progracillin as substrate,
      the enzymatic hydrolysis experiments with E1, E2, E3 and E4 were carried out
      respectively. Saponin concentrations during each biotransformation reaction were
      constructed with a kinetic model consisting of a few Michaelis-Menten equations.
      During biotransformation, C-26 glycoside and C-3 terminal glycoside were cleaved
      sequentially from saponins by E1, E2, E3 and E4. Then C-3 terminal rhamnoside and
      C-3 glycoside were released from the aglycone stepwisely by E2 and E3, to yield
      diosgenin. E2 and E3 were the key enzymes in the system, and cleavage of the C-3
      glycoside from saponins was the rate-limiting step in the biotransformation
      process. The proposed enzymatic model might be used to analyze the mechanism for
      biotransformation of saponins to diosgenin. 

PMID- 23861044
TI  - Comparative studies to assess bacterial communities on the clover phylloplane
      using MLST, DGGE and T-RFLP.
AB  - Denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment
      length polymorphism (T-RFLP) were used to characterise the changes that occurred
      in Bacillus cereus group strains present in the phylloplane of clover Trifolium
      hybridum over 4 months. These strains had previously been analysed by multiple
      locus sequence typing (MLST). DGGE displayed many equally intense bands which
      indicated many equally abundant ribotypes. The bacterial community composition
      was variable and the leaves sampled as little as a week apart were found to have
      some temporal variability, indicating that diverse phylloplane bacterial
      communities follow sequential patterns from time to time. The B. cereus group
      community clearly clustered into early, mid and late branches, possibly due to
      multiple successional sequences occurring during growing seasons. The
      functionally and phylogenetically diverse microbial communities appeared to
      exhibit predictable successional patterns over shorter time scales. DGGE analysis
      with the molecular marker rpoB gave better resolution than 16S rRNA amplicons.
      There were no strong similarities between the dendrograms produced by DGGE, MLST
      and T-RFLP and the clustering produced by the automated T-RFLP method was
      variable even between the three restriction enzymes used. The DGGE-MLST method
      emerged as a superior method to T-RFLP-MLST for rapid typing of bacterial
      communities. 

PMID- 23861045
TI  - The application of genetics and nutritional genomics in practice: an
      international survey of knowledge, involvement and confidence among dietitians in
      the US, Australia and the UK.
AB  - As a result of expanding scientific understanding of the interplay between
      genetics and dietary risk factors, those involved in nutritional management need
      to understand genetics and nutritional genomics in order to inform management of
      individuals and groups. The aim of this study was to measure and determine
      factors affecting dietitians' knowledge, involvement and confidence in genetics
      and nutritional genomics across the US, Australia and the UK. A cross-sectional
      study was undertaken using an online questionnaire that measured knowledge and
      current involvement and confidence in genetics and nutritional genomics. The
      questionnaire was distributed to dietitians in the US, Australia and the UK using
      email lists from the relevant professional associations. Data were collected from
      1,844 dietitians who had practiced in the previous 6 months. The main outcomes
      were knowledge of genetics and nutritional genomics and involvement and
      confidence in undertaking clinical and educational activities related to genetics
      and nutritional genomics. Mean scores for knowledge, involvement and confidence
      were calculated. Analysis of variance and chi (2) analysis were used to compare
      scores and frequencies. Multivariate linear regression was used to determine
      predictors of high scores. The results demonstrated significant differences in
      involvement (p < 0.001) and confidence (p < 0.001) but not knowledge scores (p =
      0.119) between countries. Overall, dietitians reported low levels of knowledge
      (mean knowledge score 56.3 %), involvement (mean number of activities undertaken
      20.0-22.7 %) and confidence (mean confidence score 25.8-29.7 %). Significant
      relationships between confidence, involvement and knowledge were observed.
      Variables relating to education, experience, sector of employment and attitudes
      were also significantly associated with knowledge, involvement and confidence.
      Dietitians' knowledge, involvement and confidence relating to genetics and
      nutritional genomics remain low and further investigation into factors
      contributing to this is required. 

PMID- 23861046
TI  - Genetic susceptibility to obesity and diet intakes: association and interaction
      analyses in the Malmo Diet and Cancer Study.
AB  - Gene-environment interactions need to be studied to better understand the
      obesity. We aimed at determining whether genetic susceptibility to obesity
      associates with diet intake levels and whether diet intakes modify the genetic
      susceptibility. In 29,480 subjects of the population-based Malmo Diet and Cancer
      Study (MDCS), we first assessed association between 16 genome-wide association
      studies identified obesity-related single-nucleotide polymorphisms (SNPs) with
      body mass index (BMI) and associated traits. We then conducted association
      analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and
      the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein,
      fiber and total energy intake, as well as interaction analyses on BMI and
      associated traits among 26,107 nondiabetic MDCS participants. GRS associated
      strongly with increased BMI (P = 3.6 * 10(-34)), fat mass (P = 6.3 * 10(-28)) and
      fat-free mass (P = 1.3 * 10(-24)). Higher GRS associated with lower total energy
      intake (P = 0.001) and higher intake of fiber (P = 2.3 * 10(-4)). No significant
      interactions were observed between GRS and the studied dietary intakes on BMI or
      related traits. Of the individual SNPs, after correcting for multiple
      comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461
      showed interaction with protein intake on BMI. In conclusion, our study does not
      provide evidence for a major role for macronutrient-, fiber- or total energy
      intake levels in modifying genetic susceptibility to obesity measured as GRS.
      However, our data suggest that the number of risk alleles as well as some of the
      individual obesity loci may have a role in regulation of food and energy intake
      and that some individual loci may interact with diet. 

PMID- 23861047
TI  - Short-term wear evaluation of thin acetabular liners on 36-mm femoral heads.
AB  - BACKGROUND: Dislocation remains the leading cause of revision THA. One approach
      to decreasing prosthetic dislocation risk has been the use of larger femoral head
      component sizes. The upper limit of head size in metal-on-polyethylene hip
      arthroplasty has historically been limited because of concerns about increased
      wear on thin polyethylene components. It is not known to what degree this concern
      should apply to more wear-resistant polyethylene components. QUESTIONS/PURPOSES:
      We therefore determined (1) in vitro wear rates of polyethylene liners of varying
      thicknesses, (2) whether there were differences in the microscopic wear
      characteristics as a function of polyethylene thickness, and (3) whether thin
      polyethylene components resulted in early catastrophic failures. METHODS: We used
      a hip wear simulator to compare the wear performance of 12 highly crosslinked
      polyethylene acetabular inserts. The internal diameter of all components was 36
      mm, and there were three samples tested of each thickness (1.9, 3.9, 5.9, or 7.9
      mm). Testing was conducted for 2.4 million cycles. Gravimetric mass loss was
      converted to volumetric loss, which was subsequently converted to theoretical
      linear penetration rates. RESULTS: Wear rates decreased with increasing
      polyethylene thickness. Mean +/- SD wear rates for the 1.9-, 3.9-, 5.9-, and 7.9
      mm groups were 5.0 +/- 0.5, 3.2 +/- 0.3, 2.5 +/- 1.1, and 2.2 +/- 1.3
      mm(3)/million cycles, respectively (p < 0.016). Calculated penetration rates were
      0.015, 0.012, 0.011, and 0.010 mm/million cycles, respectively (p < 0.016). There
      were no catastrophic failures in any group. CONCLUSIONS: Thinner polyethylene
      components demonstrated higher wear rates, although even the highest wear rate
      observed in the thinnest polyethylene specimen was lower than that commonly
      reported for noncrosslinked polyethylene components. While encouraging, these
      findings should be validated in vivo before clinical recommendations can be made.

PMID- 23861048
TI  - Image guided core needle biopsy of musculoskeletal lesions: are nondiagnostic
      results clinically useful?
AB  - BACKGROUND: The clinical utility of nondiagnostic core needle biopsies is not
      fully understood. Understanding the clinical and radiologic factors associated
      with nondiagnostic core needle biopsies may help determine the utility of these
      nondiagnostic biopsies and guide clinical decision making. QUESTIONS/PURPOSES: We
      asked (1) whether benign or malignant bone and soft tissue lesions have a higher
      rate of nondiagnostic core needle biopsy results, and which diagnoses have the
      lowest diagnostic yield; (2) how often nondiagnostic results affected clinical
      decision-making; and (3) what clinical factors are associated with nondiagnostic
      but useful core needle biopsies. METHODS: A retrospective study was performed of
      778 consecutive image-guided core needle biopsies of bone and soft tissue lesions
      referred to the musculoskeletal radiology department at a single institution. The
      reference standard was (1) the final diagnosis at surgery or (2) clinical
      followup. Diagnostic yield was calculated for the most common diagnoses. Clinical
      and imaging features related to each nondiagnostic core needle biopsy were
      assessed for their association with clinical usefulness. Useful nondiagnostic
      biopsies were defined as those that help guide treatment. Each lesion was
      assessed before biopsy by the orthopaedic oncologist as (1) "likely to be benign"
      or (2) "suspicious for malignancy." The overall diagnostic yield was 74%.
      RESULTS: Malignant lesions had higher diagnostic yield than benign lesions: 94%
      (323 of 345) versus 58% (252 of 433), yielding a relative risk (RR) of 1.61 and
      95% CI of 1.48 to 1.75. Soft tissue lesions had a higher diagnostic yield than
      bone lesions: 82% (291 of 355) versus 67% (284 of 423); RR, 1.22; 95% CI, 1.22
      (1.12-1.33). Ganglion cyst (36%, four of 11), myositis ossificans (40%, two of
      five), Langerhans cell histiocytosis (0%, 0 of four), and simple bone cyst 0%, 0
      of six) had the lowest diagnostic yield. Of the nondiagnostic biopsies assessed
      for clinical usefulness by the orthopaedic oncologist, 60% (85 of 142) of the
      biopsies were useful in guiding clinical decision making. Useful nondiagnostic
      core needle biopsy results occurred more often in painless, nonaggressive
      lesions, assessed as "likely to be benign" before biopsy. CONCLUSIONS:
      Nondiagnostic core needle biopsy results in musculoskeletal lesions are not
      entirely useless. At times, they can be supportive of benign processes and can
      help avert unnecessary surgical procedures.

PMID- 23861049
TI  - CORR Insights (r): Adverse local tissue reaction associated with a modular hip
      hemiarthroplasty.

PMID- 23861056
TI  - The mechanical control of nervous system development.
AB  - The development of the nervous system has so far, to a large extent, been
      considered in the context of biochemistry, molecular biology and genetics.
      However, there is growing evidence that many biological systems also integrate
      mechanical information when making decisions during differentiation, growth,
      proliferation, migration and general function. Based on recent findings, I
      hypothesize that several steps during nervous system development, including
      neural progenitor cell differentiation, neuronal migration, axon extension and
      the folding of the brain, rely on or are even driven by mechanical cues and
      forces. 

PMID- 23861057
TI  - Cdks, cyclins and CKIs: roles beyond cell cycle regulation.
AB  - Cyclin-dependent kinases (Cdks) are serine/threonine kinases and their catalytic
      activities are modulated by interactions with cyclins and Cdk inhibitors (CKIs).
      Close cooperation between this trio is necessary for ensuring orderly progression
      through the cell cycle. In addition to their well-established function in cell
      cycle control, it is becoming increasingly apparent that mammalian Cdks, cyclins
      and CKIs play indispensable roles in processes such as transcription, epigenetic
      regulation, metabolism, stem cell self-renewal, neuronal functions and
      spermatogenesis. Even more remarkably, they can accomplish some of these tasks
      individually, without the need for Cdk/cyclin complex formation or kinase
      activity. In this Review, we discuss the latest revelations about Cdks, cyclins
      and CKIs with the goal of showcasing their functional diversity beyond cell cycle
      regulation and their impact on development and disease in mammals. 

PMID- 23861058
TI  - RhoA and Cdc42 are required in pre-migratory progenitors of the medial ganglionic
      eminence ventricular zone for proper cortical interneuron migration.
AB  - Cortical interneurons arise from the ganglionic eminences in the ventral
      telencephalon and migrate tangentially to the cortex. Although RhoA and Cdc42,
      members of the Rho family of small GTPases, have been implicated in regulating
      neuronal migration, their respective roles in the tangential migration of
      cortical interneurons remain unknown. Here we show that loss of RhoA and Cdc42 in
      the ventricular zone (VZ) of the medial ganglionic eminence (MGE) using Olig2-Cre
      mice causes moderate or severe defects in the migration of cortical interneurons,
      respectively. Furthermore, RhoA- or Cdc42-deleted MGE cells exhibit impaired
      migration in vitro. To determine whether RhoA and Cdc42 directly regulate the
      motility of cortical interneurons during migration, we deleted RhoA and Cdc42 in
      the subventricular zone (SVZ), where more fate-restricted progenitors are located
      within the ganglionic eminences, using Dlx5/6-Cre-ires-EGFP (Dlx5/6-CIE) mice.
      Deletion of either gene within the SVZ does not cause any obvious defects in
      cortical interneuron migration, indicating that cell motility is not dependent
      upon RhoA or Cdc42. These findings provide genetic evidence that RhoA and Cdc42
      are required in progenitors of the MGE in the VZ, but not the SVZ, for proper
      cortical interneuron migration. 

PMID- 23861059
TI  - Cell and tissue dynamics during Tribolium embryogenesis revealed by versatile
      fluorescence labeling approaches.
AB  - Studies on new arthropod models such as the beetle Tribolium castaneum are
      shifting our knowledge of embryonic patterning and morphogenesis beyond the
      Drosophila paradigm. In contrast to Drosophila, Tribolium embryos exhibit the
      short-germ type of development and become enveloped by extensive extra-embryonic
      membranes, the amnion and serosa. The genetic basis of these processes has been
      the focus of active research. Here, we complement genetic approaches with live
      fluorescence imaging of Tribolium embryos to make the link between gene function
      and morphogenetic cell behaviors during blastoderm formation and differentiation,
      germband condensation and elongation, and extra-embryonic development. We first
      show that transient labeling methods result in strong, homogeneous and persistent
      expression of fluorescent markers in Tribolium embryos, labeling the chromatin,
      membrane, cytoskeleton or combinations thereof. We then use co-injection of
      fluorescent markers with dsRNA for live imaging of embryos with disrupted caudal
      gene function caused by RNA interference. Using these approaches, we describe and
      compare cell and tissue dynamics in Tribolium embryos with wild-type and altered
      fate maps. We find that Tribolium germband condensation is effected by cell
      contraction and intercalation, with the latter being dependent on the anterior
      posterior patterning system. We propose that germband condensation drives
      initiation of amnion folding, whereas expansion of the amniotic fold and closure
      of the amniotic cavity are likely driven by contraction of an actomyosin cable at
      the boundary between the amnion and serosa. Our methodology provides a
      comprehensive framework for testing quantitative models of patterning, growth and
      morphogenetic mechanisms in Tribolium and other arthropod species. 

PMID- 23861060
TI  - Phagocytic receptor signaling regulates clathrin and epsin-mediated cytoskeletal
      remodeling during apoptotic cell engulfment in C. elegans.
AB  - The engulfment and subsequent degradation of apoptotic cells by phagocytes is an
      evolutionarily conserved process that efficiently removes dying cells from animal
      bodies during development. Here, we report that clathrin heavy chain (CHC-1), a
      membrane coat protein well known for its role in receptor-mediated endocytosis,
      and its adaptor epsin (EPN-1) play crucial roles in removing apoptotic cells in
      Caenorhabditis elegans. Inactivating epn-1 or chc-1 disrupts engulfment by
      impairing actin polymerization. This defect is partially suppressed by
      inactivating UNC-60, a cofilin ortholog and actin server/depolymerization
      protein, further indicating that EPN-1 and CHC-1 regulate actin assembly during
      pseudopod extension. CHC-1 is enriched on extending pseudopods together with EPN
      1, in an EPN-1-dependent manner. Epistasis analysis places epn-1 and chc-1 in the
      same cell-corpse engulfment pathway as ced-1, ced-6 and dyn-1. CED-1 signaling is
      necessary for the pseudopod enrichment of EPN-1 and CHC-1. CED-1, CED-6 and DYN
      1, like EPN-1 and CHC-1, are essential for the assembly and stability of F-actin
      underneath pseudopods. We propose that in response to CED-1 signaling, CHC-1 is
      recruited to the phagocytic cup through EPN-1 and acts as a scaffold protein to
      organize actin remodeling. Our work reveals novel roles of clathrin and epsin in
      apoptotic-cell internalization, suggests a Hip1/R-independent mechanism linking
      clathrin to actin assembly, and ties the CED-1 pathway to cytoskeleton
      remodeling. 

PMID- 23861061
TI  - Short-lived Her proteins drive robust synchronized oscillations in the zebrafish
      segmentation clock.
AB  - Oscillations are prevalent in natural systems. A gene expression oscillator,
      called the segmentation clock, controls segmentation of precursors of the
      vertebral column. Genes belonging to the Hes/her family encode the only conserved
      oscillating genes in all analyzed vertebrate species. Hes/Her proteins form
      dimers and negatively autoregulate their own transcription. Here, we developed a
      stochastic two-dimensional multicellular computational model to elucidate how the
      dynamics, i.e. period, amplitude and synchronization, of the segmentation clock
      are regulated. We performed parameter searches to demonstrate that autoregulatory
      negative-feedback loops of the redundant repressor Her dimers can generate
      synchronized gene expression oscillations in wild-type embryos and reproduce the
      dynamics of the segmentation oscillator in different mutant conditions. Our model
      also predicts that synchronized oscillations can be robustly generated as long as
      the half-lives of the repressor dimers are shorter than 6 minutes. We validated
      this prediction by measuring, for the first time, the half-life of Her7 protein
      as 3.5 minutes. These results demonstrate the importance of building biologically
      realistic stochastic models to test biological models more stringently and make
      predictions for future experimental studies. 

PMID- 23861062
TI  - Pdgfra protects against ethanol-induced craniofacial defects in a zebrafish model
      of FASD.
AB  - Human birth defects are highly variable and this phenotypic variability can be
      influenced by both the environment and genetics. However, the synergistic
      interactions between these two variables are not well understood. Fetal alcohol
      spectrum disorders (FASD) is the umbrella term used to describe the wide range of
      deleterious outcomes following prenatal alcohol exposure. Although FASD are
      caused by prenatal ethanol exposure, FASD are thought to be genetically
      modulated, although the genes regulating sensitivity to ethanol teratogenesis are
      largely unknown. To identify potential ethanol-sensitive genes, we tested five
      known craniofacial mutants for ethanol sensitivity: cyp26b1, gata3, pdgfra, smad5
      and smoothened. We found that only platelet-derived growth factor receptor alpha
      (pdgfra) interacted with ethanol during zebrafish craniofacial development.
      Analysis of the PDGF family in a human FASD genome-wide dataset links PDGFRA to
      craniofacial phenotypes in FASD, prompting a mechanistic understanding of this
      interaction. In zebrafish, untreated pdgfra mutants have cleft palate due to
      defective neural crest cell migration, whereas pdgfra heterozygotes develop
      normally. Ethanol-exposed pdgfra mutants have profound craniofacial defects that
      include the loss of the palatal skeleton and hypoplasia of the pharyngeal
      skeleton. Furthermore, ethanol treatment revealed latent haploinsufficiency,
      causing palatal defects in ~62% of pdgfra heterozygotes. Neural crest apoptosis
      partially underlies these ethanol-induced defects in pdgfra mutants,
      demonstrating a protective role for Pdgfra. This protective role is mediated by
      the PI3K/mTOR pathway. Collectively, our results suggest a model where combined
      genetic and environmental inhibition of PI3K/mTOR signaling leads to variability
      within FASD. 

PMID- 23861063
TI  - Systematic quantification of developmental phenotypes at single-cell resolution
      during embryogenesis.
AB  - Current imaging technology provides an experimental platform in which complex
      developmental processes can be observed at cellular resolution over an extended
      time frame. New computational tools are essential to achieve a systems-level
      understanding of this high-content information. We have devised a structured
      approach to systematically analyze complex in vivo phenotypes at cellular
      resolution, which divides the task into a panel of statistical measurements of
      each cell in terms of cell differentiation, proliferation and morphogenesis,
      followed by their spatial and temporal organization in groups and the cohesion
      within the whole specimen. We demonstrate the approach to C. elegans
      embryogenesis with in toto imaging and automated cell lineage tracing. We define
      statistical distributions of the wild-type developmental behaviors at single-cell
      resolution based on over 50 embryos, cumulating in over 4000 distinct,
      developmentally based measurements per embryo. These methods enable statistical
      quantification of abnormalities in mutant or RNAi-treated embryos and a rigorous
      comparison of embryos by testing each measurement for the probability that it
      would occur in a wild-type embryo. We demonstrate the power of this structured
      approach by uncovering quantitative properties including subtle phenotypes in
      both wild-type and perturbed embryos, transient behaviors that lead to new
      insights into gene function and a previously undetected source of developmental
      noise and its subsequent correction. 

PMID- 23861064
TI  - Three-dimensional culture and cAMP signaling promote the maturation of human
      pluripotent stem cell-derived hepatocytes.
AB  - Human pluripotent stem cells (hPSCs) represent a novel source of hepatocytes for
      drug metabolism studies and cell-based therapy for the treatment of liver
      diseases. These applications are, however, dependent on the ability to generate
      mature metabolically functional cells from the hPSCs. Reproducible and efficient
      generation of such cells has been challenging to date, owing to the fact that the
      regulatory pathways that control hepatocyte maturation are poorly understood.
      Here, we show that the combination of three-dimensional cell aggregation and cAMP
      signaling enhance the maturation of hPSC-derived hepatoblasts to a hepatocyte
      like population that displays expression profiles and metabolic enzyme levels
      comparable to those of primary human hepatocytes. Importantly, we also
      demonstrate that generation of the hepatoblast population capable of responding
      to cAMP is dependent on appropriate activin/nodal signaling in the definitive
      endoderm at early stages of differentiation. Together, these findings provide new
      insights into the pathways that regulate maturation of hPSC-derived hepatocytes
      and in doing so provide a simple and reproducible approach for generating
      metabolically functional cell populations. 

PMID- 23861065
TI  - Neuroimaging of resilience to stress: current state of affairs.
AB  - Resilience is defined as a dynamic, multidimensional process encompassing
      positive adaptation within the context of significant adversity. The complex
      nature of this construct makes it a difficult topic to study in neuroimaging
      research; however, in this article, we propose ways to operationalize resilience.
      The limited amount of structural and functional neuroimaging studies specifically
      designed to examine resilience have mainly focused on investigating alterations
      in regions of the brain involved in emotion and stress regulation circuitry. In
      the future, neuroimaging of resilience is expected to benefit from functional and
      structural connectivity approaches and the use of novel imaging task paradigms.

PMID- 23861066
TI  - CD4+ T cell count, HIV-1 viral loads and demographic variables of newly
      identified patients with HIV infection in Wuhan, China.
AB  - In China, the rate of human immunodeficiency virus (HIV) testing is increasing
      among men who have sex with men. The purpose of the present study was to describe
      HIV-related biomarkers and selected demographic variables of persons with newly
      diagnosed HIV/AIDS, among men who have sex with men in particular, in Wuhan
      China. Demographic indicators, and CD4+ T cell counts and HIV-1 viral load were
      collected from individuals newly identified as HIV-1 antibody positive during
      2011. Of 176 enrolled patients, 132 (75.0%) were men who have sex with men. This
      group was significantly younger and had higher CD4+ T cell counts than patients
      who were likely infected through heterosexual contact. Most men who have sex with
      men (56.6%) were discovered by initiative investigation. Among heterosexual
      patients CD4+ T cell counts and HIV-1 viral load were significantly correlated;
      among the group of men who have sex with men, no such association was found.

PMID- 23861068
TI  - High throughput strategies for probing the different organizational levels of
      protein interaction networks.
AB  - Most proteins do not exist as isolated molecules in the cell, but instead serve
      as nodes of protein interaction networks. A number of techniques have been
      developed in the last two decades to study protein interaction networks at
      different levels of detail. Here we describe some of the techniques for
      characterizing protein interactions and protein complexes on a system-wide scale,
      focusing especially on newly emerging techniques that use co-migration. These
      newer approaches have the advantage that no genetic manipulation is necessary,
      thereby allowing investigation of protein complexes at their endogenous levels in
      the correct cellular context. Finally, we discuss different approaches for
      measuring large-scale temporal changes to protein interaction networks, an area
      that we believe will be one of the frontiers in systems biology in the coming
      years. 

PMID- 23861067
TI  - Fluphenazine (oral) versus placebo for schizophrenia.
AB  - BACKGROUND: Fluphenazine is one of the first drugs to be classed as an
      'antipsychotic' and has been widely available for five decades. OBJECTIVES: To
      compare the effects of oral fluphenazine with placebo for the treatment of
      schizophrenia. SEARCH METHODS: We updated searches of the Cochrane Schizophrenia
      Group's trials register, which includes relevant randomised controlled trials
      from the bibliographic databases Biological Abstracts, CINAHL, The Central
      Register of Controlled Trials in The Cochrane Library, EMBASE, MEDLINE, PsycLIT,
      LILACS, PSYNDEX, Sociological Abstracts and Sociofile, 15 May, 2012. References
      of all identified studies were searched for further trial citations. SELECTION
      CRITERIA: We sought all randomised controlled trials comparing oral fluphenazine
      with placebo relevant to people with schizophrenia. Primary outcomes of interest
      were global state and adverse effects. DATA COLLECTION AND ANALYSIS: We inspected
      citations and abstracts independently, ordered papers and re-inspected and
      quality assessed trials. We extracted data independently. Dichotomous data were
      analysed using fixed-effect risk ratio (RR) and the 95% confidence interval (CI).
      Continuous data were excluded if more than 50% of people were lost to follow-up,
      but, where possible, mean differences (MD) were calculated. MAIN RESULTS: From
      over 1200 electronic records of 415 studies identified by our initial search and
      this updated search, we excluded 48 potentially relevant studies and included
      seven trials published between 1964 and 1999 that randomised 439 (mostly adult
      participants). No new included trials were identified for this review update.
      Compared with placebo, global state outcomes of 'not improved or worsened' were
      not significantly different in the medium term in one small study (n = 50, 1 RCT,
      RR 1.12 CI 0.79 to 1.58, very low quality of evidence). The risk of relapse in
      the long term was greater in two small studies in people receiving placebo (n =
      86, 2 RCTs, RR 0.39 CI 0.05 to 3.31, very low quality of evidence), however with
      high degree of heterogeneity in the results. Only one person allocated
      fluphenazine was reported in the same small study to have died on long-term
      follow-up (n = 50, 1 RCT, RR 2.38 CI 0.10 to 55.72, low quality of evidence).
      Short-term extrapyramidal adverse effects were significantly more frequent with
      fluphenazine compared to placebo in two other studies for the outcomes of
      akathisia (n = 227, 2 RCTs, RR 3.43 CI 1.23 to 9.56, moderate quality of
      evidence) and rigidity (n = 227, 2 RCTs, RR 3.54 CI 1.76 to 7.14, moderate
      quality of evidence). AUTHORS' CONCLUSIONS: The findings in this review confirm
      much that clinicians and recipients of care already know, but they provide
      quantification to support clinical impression. Fluphenazine's global position as
      an effective treatment for psychoses is not threatened by the outcome of this
      review. However, fluphenazine is an imperfect treatment and if accessible, other
      inexpensive drugs less associated with adverse effects may be an equally
      effective choice for people with schizophrenia.

PMID- 23861069
TI  - Attitudes and beliefs regarding cardiovascular risk factors among Bangladeshi
      immigrants in the US.
AB  - The US has increasingly growing Bangladeshi population, a South Asian sub-ethnic
      group with a high prevalence of cardiovascular disease (CVD). We conducted a
      qualitative study using individual in-depth interviews to explore attitudes
      towards and difficulties with modifying CVD related behaviors among a Bangladeshi
      cohort. We interviewed 55 patients before reaching data saturation. Bangladeshis
      discussed the meaning of health and heart disease in the context of how disease
      can potentially impact their ability to care for their family. Behavioral and
      psychological factors were discussed as the causes of CVD. Internal forces and
      external forces were brought up to explain difficulties addressing the causes of
      CVD. Bangladeshi individuals in our study were aware of CVD, but felt unable to
      address behavioral risk factors. They cite a combination of internal and external
      factors as barriers to lifestyle modification. Interventions to address these
      barriers must simultaneously addressing self-efficacy and work-life balance. 

PMID- 23861070
TI  - Bax phosphorylation association with nucleus and oligomerization after neonatal
      hypoxia-ischemia.
AB  - Neonatal hypoxia-ischemia (HI) is a common occurrence in preterm and low-birth
      weight infants, and the incidence of low-birth-weight and preterm births is
      increasing. Characterization of brain injury after HI is of critical importance
      in developing new treatments that more accurately target the injury. After severe
      HI, neuronal cells undergo necrosis and secondary apoptosis of the surrounding
      cells as a result of neuroinflammation. We sought to characterize the biochemical
      pathways associated with cell death after HI. Bax, a cell death signaling
      protein, is activated after HI and translocates to the nucleus, endoplasmic
      reticulum, and mitochondria. The translocation patterns of Bax affect the
      resultant cell death phenotype (necrotic or apoptotic) observed. Although Bax is
      known to oligomerize once it is activated, less is known about the factors that
      control its translocation and oligomerization. We hypothesize that Bax kinase
      specific phosphorylation determines its oligomerization and intracellular
      localization. Using well-established in vivo and in vitro models of neonatal HI,
      we characterized Bax oligomerization and multiorganelle translocation. We found
      that HI-dependent phosphorylation of Bax determines its oligomerization status
      and multiorganelle localization, and, ultimately, the cell death phenotype
      observed. Understanding the mechanisms of Bax translocation will aid in the
      rational design of therapeutic strategies that decrease the trauma resulting from
      HI-associated inflammation.

PMID- 23861071
TI  - Increased neuronal survival in the brainstem during liver injury: role of gamma
      aminobutyric acid and serotonin chitosan nanoparticles.
AB  - gamma-Aminobutyric acid (GABA)- and serotonin (5-HT)-mediated cell signaling,
      neuronal survival enhancement, and reduced neuronal death in brainstem during
      liver injury followed by active liver regeneration have a critical role in
      maintaining routine bodily functions. In the present study, GABAB and 5-HT2A
      receptor functional regulation, interrelated actions of neuronal survival
      factors, and expression of apoptotic factors in the brainstem during GABA and 5
      HT chitosan nanoparticles-induced active liver regeneration in partially
      hepatectomized rats were evaluated. Partially hepatectomized rats were treated
      with the nanoparticles, and receptor assays and confocal microscopic studies of
      GABAB and 5-HT2A receptors, gene expression studies of GABAB and 5-HT2A
      receptors, nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF
      alpha), Akt-1, phospholipase C, Bax, and caspase-8 were performed with the
      brainstems of experimental animals. A significant decrease in GABAB and 5-HT2A
      receptor numbers and gene expressions denoted a homeostatic adjustment by the
      brain to trigger the sympathetic innervations during elevated DNA synthesis in
      the liver. The neuronal apoptosis resulting from the loss of liver function after
      partial hepatectomy was minimized by nanoparticle treatment in rats compared with
      rats with no treatment during regeneration. This was confirmed from the gene
      expression patterns of NF-kappaB, TNF-alpha, Akt-1, phospholipase C, Bax, and
      caspase-8. The present study revealed the potential of GABA and 5-HT chitosan
      nanoparticles for increasing neuronal survival in the brainstem during liver
      injury following regeneration, which avoids many neuropsychiatric problems.

PMID- 23861072
TI  - Methyl 3,4-dihydroxybenzoate protects primary cortical neurons against Abeta25-35
      induced neurotoxicity through mitochondria pathway.
AB  - Amyloid-beta peptides (Abeta), which can aggregate into oligomers or fibrils in
      neurons, play a critical role in the pathogenesis of Alzheimer's disease (AD).
      Methyl 3,4-dihydroxybenzoate (MDHB), a phenolic acid compound, has been reported
      to have antioxidative and neurotrophic effects. The present study investigated
      the neuroprotective effects of MDHB against Abeta-induced apoptosis in rat
      primary cortical neutons. The primary cortical neurons were pretreated with
      different concentrations of MDHB for 24 hr, then incubated with 10 MUM Abeta25-35
      for 24 hr. The results showed that Abeta25-35 could induce neurotoxicity as
      evidenced by the decreased cell viability and the increased apoptotic rate. In
      parallel, Abeta25-35 significantly increased the reactive oxygen species
      accumulation and decreased mitochondrial membrane potential. However,
      pretreatment of the primary cortical neurons with MDHB could effectively suppress
      these cellular events caused by Abeta25-35 exposure. In addition, MDHB could
      increase the level of Bcl-2, decrease the level of Bax, and inhibit the
      activation of caspase-9 and caspase-3 in Abeta25-35 -treated primary cortical
      neurons. All these results were beneficial in their protective effect against
      Abeta-induced neurotoxicity. Our results suggest that MDHB has a neuroprotective
      effect that provides a pharmacological basis for its clinical use in the
      treatment of AD.

PMID- 23861073
TI  - Chryseobacterium indologenes catheter-related meningitis in an elderly patient
      after intracranial aneurysm clipping surgery.

PMID- 23861074
TI  - Hippocampal expression of aryl hydrocarbon receptor nuclear translocator 2 and
      neuronal PAS domain protein 4 in a rat model of depression.
AB  - The transcription factors aryl hydrocarbon receptor nuclear translocator 2
      (ARNT2) and neuronal PAS domain protein 4 (NPAS4) may influence emotion and
      cognitive function by regulating brain-derived neurotrophic factor expression in
      the hippocampus. We estimated hippocampal ARNT2 and NPAS4 expression in chronic
      unexpected mild stress (CUMS) rat model. The possible association was
      investigated between expression of these transcription factors and depressive
      behaviors. Behavioral tests were conducted before, during, and after 28 days of
      group housing or isolation plus CUMS. The sucrose solution consumption test was
      used to assess changes in interest and pleasure-seeking, and the open field test
      (OFT) was conducted to measure spontaneous activity and exploratory behavior.
      Expression levels of ARNT2 and NPAS4 were estimated by semiquantitative reverse
      transcription-polymerase chain reaction (RT-PCR). Compared to controls, rats
      subjected to isolation plus CUMS exhibited significantly reduced weight gain (t =
      9.317, P = 0.000), sucrose consumption (t = 3.756, P = 0.003), horizontal
      ambulation (t = 2.362, P = 0.041), and number of rearings (vertical motion) (t =
      2.268, P = 0.040). Relative hippocampal NPAS4 expression was significantly lower
      in depression model rats compared to controls (t = 2.995, P = 0.010) but there
      was no significant difference in hippocampal ARNT2 expression between groups (t =
      0.091, P = 0.929). The relationship between the CUMS model of depression and
      NPAS4 expression requires further exploration.

PMID- 23861076
TI  - In vitro pituitary and thyroid cell proliferation assays and their relevance as
      alternatives to animal testing.
AB  - This study investigates the in vitro effect of eleven thyroid-active compounds
      known to affect pituitary and/or thyroid weights in vivo, using the proliferation
      of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid
      cells in a newly developed test denoted "TSH-screen" to gain insight into the
      relative value of these in vitro proliferation tests for an integrated testing
      strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen
      was stimulated by three out of eleven tested compounds, namely thyrotropin
      releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three
      compounds, only T4 causes an increase in relative pituitary weight, and thus T4
      was the only compound for which the effect in the in vitro assay correlated with
      a reported in vivo effect. As to the newly developed TSH-screen, two compounds
      had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4
      antagonized FRTL-5 cell proliferation. These effects correlated with in vivo
      changes induced by these compounds on thyroid weight. Altogether, the results
      indicate that most of the selected compounds affect pituitary and thyroid weights
      by modes of action different from a direct thyroid hormone receptor (THR) or TSH
      receptor (TSHR)-mediated effect, and point to the need for additional in vitro
      tests for an ITS. Additional analysis of the T-screen revealed a positive
      correlation between the THR-mediated effects of the tested compounds in vitro and
      their effects on relative heart weight in vivo, suggesting that the T-screen may
      directly predict this THR-mediated in vivo adverse effect.

PMID- 23861077
TI  - Predictive value of cell assays for developmental toxicity and embryotoxicity of
      conazole fungicides.
AB  - This paper evaluates in vivo predictability of a battery of in vitro tests
      covering developmental toxicity and embryotoxicity of five widely used conazole
      fungicides. The conazoles were investigated in the embryonic stem cell test, and
      data were compared to in vivo embryotoxicity data. The same conazoles were
      evaluated on the basis of data from a battery of cell assays for endocrine
      activity, including assays for AR, ER, AhR, and sex hormone synthesis, and data
      were compared to in vivo developmental toxicity data. Overall, the ranking of the
      five conazole fungicides based on in vitro data were in reasonably good agreement
      with available in vivo effects. Ketoconazole and epoxiconazole are the most
      potent embryotoxic compounds, whereas prochloraz belongs to the most potent
      developmental toxicants. In conclusion, a rough prediction of the ranking of
      these conazole fungicides for in vivo toxicity data was possible by a holistic
      evaluation of data from a panel of cell-based assays.

PMID- 23861075
TI  - Look back in anger - what clinical studies tell us about preclinical work.
AB  - Misled by animal studies and basic research? Whenever we take a closer look at
      the outcome of clinical trials in a field such as, most recently, stroke or
      septic shock, we see how limited the value of our preclinical models was. For all
      indications, 95% of drugs that enter clinical trials do not make it to the
      market, despite all promise of the (animal) models used to develop them. Drug
      development has started already to decrease its reliance on animal models: In
      Europe, for example, despite increasing R&D expenditure, animal use by
      pharmaceutical companies dropped by more than 25% from 2005 to 2008. In vitro
      studies are likewise limited: questionable cell authenticity, over-passaging,
      mycoplasma infections, and lack of differentiation as well as non-homeostatic and
      non-physiologic culture conditions endanger the relevance of these models. The
      standards of statistics and reporting often are poor, further impairing
      reliability. Alarming studies from industry show miserable reproducibility of
      landmark studies. This paper discusses factors contributing to the lack of
      reproducibility and relevance of pre-clinical research. THE CONCLUSION: Publish
      less but of better quality and do not rely on the face value of animal studies.

PMID- 23861078
TI  - In vitro metabolism and bioavailability tests for endocrine active substances:
      what is needed next for regulatory purposes?
AB  - Legislation and prospective legislative proposals internationally (may) require
      that chemicals be tested for their ability to disrupt the hormonal systems of
      mammals. Chemicals found to test positive in vitro are considered to be endocrine
      active substances (EAS) and may be putative endocrine disruptors (EDs) in vivo.
      While there is a growing body of international in vitro test guidelines
      addressing EAS mechanisms and modes of action, to date there are still few or no
      standardized methods to incorporate metabolic and toxicokinetic aspects into
      these in vitro tests for EAS. In vitro assays for EAS should incorporate
      metabolic enzyme systems to better address the relevance of EAS tests to in vivo
      adverse outcome pathways, and a previous OECD review paper indicated how this
      could be done. This paper revisits those recommendations, addressing where
      research and funding efforts are needed to expedite the development of suitable
      in vitro metabolism systems to improve the accuracy of in vitro assays for
      identifying EAS and EDs. Recommendations are made for projects to support short,
      medium, and long-term goals. The complexity of in vivo metabolism presents major
      challenges for the development of predictive models suitable for the
      extrapolation of data from in silico/in vitro approaches to models that can occur
      in vivo. Therefore, the long-term recommendations are intended to foster an
      international harmonization of databases, delineation of metabolic pathways, and
      development of predictive tools that will provide a fundamental understanding of
      the processes by which metabolism occurs, increasing the predictive accuracy of
      in silico/in vitro methods.

PMID- 23861079
TI  - In vitro testicular toxicity models: opportunities for advancement via biomedical
      engineering techniques.
AB  - To address the pressing need for better in vitro testicular toxicity models, a
      workshop sponsored by the International Life Sciences Institute (ILSI), the
      Health and Environmental Science Institute (HESI), and the Johns Hopkins Center
      for Alternatives to Animal Testing (CAAT), was held at the Mt. Washington
      Conference Center in Baltimore, MD, USA on October 26-27, 2011. At this workshop,
      experts in testis physiology, toxicology, and tissue engineering discussed
      approaches for creating improved in vitro environments that would be more
      conducive to maintaining spermatogenesis and steroidogenesis and could provide
      more predictive models for testicular toxicity testing. This workshop report is
      intended to provide scientists with a broad overview of relevant testicular
      toxicity literature and to suggest opportunities where bioengineering principles
      and techniques could be used to build improved in vitro testicular models for
      safety evaluation. Tissue engineering techniques could, conceivably, be
      immediately implemented to improve existing models. However, it is likely that in
      vitro testis models that use single or multiple cell types will be needed to
      address such endpoints as accurate prediction of chemically induced testicular
      toxicity in humans, elucidation of mechanisms of toxicity, and identification of
      possible biomarkers of testicular toxicity.

PMID- 23861080
TI  - Alternative methods: 3Rs, research and regulatory aspects.

PMID- 23861081
TI  - Bayesian network integrated testing strategy and beyond.
AB  - In a recent series of papers written by Jaworska with different coauthors,
      compelling reasons for adopting a probabilistic approach to Integrated Testing
      Strategies were detailed. In a case study on skin sensitization, a Bayesian
      Network proved to be effective in adapting testing strategies to the available
      evidence. There is no doubt that probabilistic Integrated Testing Strategies are
      one way to pursue the goals of 3Rs effectively; nevertheless, some issues deserve
      further comment to pinpoint statistical criticalities and to widen the
      methodological perspective towards Bayesian graphical models.

PMID- 23861082
TI  - Reply to: Bayesian network integrated testing strategy and beyond.

PMID- 23861084
TI  - Scientifically unfounded precaution drives European Commission's recommendations
      on EDC regulation, while defying common sense, well-established science and risk
      assessment principles.

PMID- 23861085
TI  - In vitro to human in vivo translation - pharmacokinetics and pharmacodynamics of
      quinidine.
AB  - The translational sciences aim to transfer results from basic research to the
      treatment of animals or patients. One of the approaches that could be utilized to
      achieve this goal is the in vitro-in vivo extrapolation (IVIVE) of
      pharmacokinetic (PK) and pharmacodynamic (PD) properties using in silico methods.
      Such methodology, if properly applied, could help substantially reduce the use of
      animals in pre-clinical research. Here, quinidine was chosen as an example of a
      drug with cardiac effects and results of nine published clinical studies
      describing its PK (plasma concentration) and PD (QTcB/?QTcB) effects were
      mimicked by combination of the IVIVE platform Simcyp (pharmacokinetics
      prediction) with the ToxComp (cardiac effect prediction) system, based
      exclusively on in vitro data. The results show that reliable QT prediction is
      possible using the mechanistic IVIVE of the PK and PD effects. This can be
      considered a proof-of-concept that also could be applied as a drug safety
      evaluation procedure.

PMID- 23861086
TI  - A comparative study of the speeds attained by captive cheetahs during the
      enrichment practice of the "cheetah run".
AB  - The enrichment practice of the "cheetah run" is becoming increasingly popular
      within zoological institutions as a method to enrich captive cheetahs. A lure
      moving at speed represents an artificial prey item that the cursorial cheetah can
      pursue, therefore allowing it to perform an important hunting behavior within a
      captive setting. This study was conducted in order to highlight how employing
      different forms of this type of enrichment may influence its efficacy. This is
      important in relation to the future development of an optimum type of "cheetah
      run" enrichment which maximizes the potential beneficial effects and therefore
      positively impacts upon cheetah welfare in captivity. Video recordings were
      carried out at three separate institutions (Fota Wildlife Park, Ireland; Ann van
      Dyk Cheetah Centre, South Africa; Cheetah Conservation Fund, Namibia).
      Randomization tests were carried out to compare the highest speeds attained
      between males and females, trained and untrained cheetahs and also between the
      three institutions. Females and trained individuals reached significantly higher
      speeds compared with males and untrained individuals, respectively. The only
      significant difference between the three institutions was between the Ann van Dyk
      Cheetah Centre and the Cheetah Conservation Fund, where cheetahs at the Ann van
      Dyk center reached significantly higher speeds. The current study represents the
      first detailed study of any aspect of the "cheetah run" across multiple
      institutions. It also includes the first quantification of the speed of cheetahs
      in captivity in relation to differing enrichment practices.

PMID- 23861087
TI  - Development of a simple pressure and heat stimulator for intra- and interdigit
      functional magnetic resonance imaging.
AB  - For this study, we developed a simple pressure and heat stimulator that can
      quantitatively control pressure and provide heat stimulation to intra- and
      interdigit areas. The developed stimulator consists of a control unit, drive
      units, and tactors. The control unit controls the stimulation parameters, such as
      stimulation types, intensity, time, and channel, and transmits a created signal
      of stimulation to the drive units. The drive units operate pressure and heat
      tactors in response to commands from the control unit. The pressure and heat
      tactors can display various stimulation intensities quantitatively, apply
      stimulation continuously, and adjust the stimulation areas. Additionally, they
      can easily be attached to and detached from the digits. The developed pressure
      and heat stimulator is small in total size, easy to install, and inexpensive to
      manufacture. The new stimulator operated stably in a magnetic resonance imaging
      (MRI) environment without affecting the obtained images. A preliminary functional
      magnetic resonance imaging (fMRI) experiment confirmed that differences in
      activation of somatosensory areas were induced from the pressure and heat
      stimulation. The developed pressure and heat stimulator is expected to be
      utilized for future intra- and interdigit fMRI studies on pressure and heat
      stimulation. 

PMID- 23861088
TI  - A pilot study of triple therapy with telaprevir, peginterferon and ribavirin for
      elderly patients with genotype 1 chronic hepatitis C.
AB  - The prevalence of hepatitis C virus (HCV) infection in elderly patients has been
      increasing in Japan. However, there are no reports on the safety and efficacy of
      the triple therapy of telaprevir, peginterferon, and ribavirin for elderly
      patients with chronic HCV infection. This study evaluated the safety and efficacy
      of triple therapy [12 weeks of telaprevir 1,500 mg/day, reduction dose, and 24
      weeks of peginterferon and ribavirin] in 18 elderly Japanese patients aged >65
      years, with chronic infection with HCV genotype 1b. Four patients received triple
      therapy with telaprevir 2,250 mg/day and the other 14 patients received
      telaprevir 1,500 mg/day. Sustained virological response-12 (HCV RNA negativity at
      12 weeks after completion of therapy) was 50% (9 of 18 patients); while 4 of 18
      (22%) patients discontinued triple therapy due to adverse events (skin rashes,
      anemia, poor appetite). The dose of telaprevir did not affect HCV RNA clearance
      rates. Regardless of the dose, 50% of the treated patients achieved sustained
      virological response-12, evaluated by intention-to-treat analysis. Furthermore,
      the fall in hemoglobin and the rise in serum creatinine were significantly milder
      in the telaprevir 1,500 mg group than the telaprevir 2,250 mg/day group. Further
      analysis showed that 67% (6 of 9 elderly patients) with IL28B gene (rs8099917)
      genotype TT, treated with telaprevir 1,500 mg, achieved sustained virological
      response-12. These results suggest that 24-week triple therapy with telaprevir
      1,500 mg seems safe and efficacious for elderly Japanese patients infected with
      HCV genotype 1b.

PMID- 23861089
TI  - Local synchronization and amplitude of the fluctuation of spontaneous brain
      activity in attention-deficit/hyperactivity disorder: a resting-state fMRI study.
AB  - Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF)
      are two approaches to depicting different regional characteristics of resting
      state functional magnetic resonance imaging (RS-fMRI) data. Whether they can
      complementarily reveal brain regional functional abnormalities in attention
      deficit/hyperactivity disorder (ADHD) remains unknown. In this study, we applied
      ReHo and ALFF to 23 medication-naive boys diagnosed with ADHD and 25 age-matched
      healthy male controls using whole-brain voxel-wise analysis. Correlation analyses
      were conducted in the ADHD group to investigate the relationship between the
      regional spontaneous brain activity measured by the two approaches and the
      clinical symptoms of ADHD. We found that the ReHo method showed widely
      distributed differences between the two groups in the fronto-cingulo-occipito
      cerebellar circuitry, while the ALFF method showed a difference only in the right
      occipital area. When a larger smoothing kernel and a more lenient threshold were
      used for ALFF, more overlapped regions were found between ALFF and ReHo, and ALFF
      even found some new regions with group differences. The ADHD symptom scores were
      correlated with the ReHo values in the right cerebellum, dorsal anterior
      cingulate cortex and left lingual gyrus in the ADHD group, while no correlation
      was detected between ALFF and ADHD symptoms. In conclusion, ReHo may be more
      sensitive to regional abnormalities, at least in boys with ADHD, than ALFF. And
      ALFF may be complementary to ReHo in measuring local spontaneous activity.
      Combination of the two may yield a more comprehensive pathophy-siological
      framework for ADHD. 

PMID- 23861091
TI  - Trends in the occurrence of high-grade anal intraepithelial neoplasia in San
      Francisco: 2000-2009.
AB  - BACKGROUND: Although screening of human immunodeficiency virus (HIV)-positive
      individuals for anal intraepithelial neoplasia (AIN; a precursor of anal cancer)
      has been practiced in San Francisco among HIV health care providers since the
      early 1990s, to the authors' knowledge no study to date has focused on evaluating
      recent AIN trends. METHODS: Cases of high-grade AIN 3 and invasive anal cancer
      from 2000 to 2009 were obtained from the San Francisco/Oakland Surveillance,
      Epidemiology, and End Results (SEER) population-based cancer registry. Age
      standardized rates of AIN 3 and anal cancer were calculated overall and by
      demographic characteristics (sex, race, and age group). Log-linear regression
      calculated annual percent change in rates during 2000 to 2009, and rate ratios
      (RRs) and 95% confidence intervals (95% CIs), evaluated differences in rates
      during 2000 through 2004 and 2005 through 2009. RESULTS: During 2000 through
      2009, the majority of AIN 3 cases occurred among men (1152 of 1320 men; 87.3%).
      Rates of AIN 3 during the corresponding period increased by 11.48% per year (P <
      .05) among men and were stable among women. Comparing rates among men during 2000
      to 2004 with those during 2005 to 2009, the largest increases were noted among
      those aged 50 years to 64 years (RR, 2.47; 95% CI, 1.93-3.17) and among black
      individuals (RR, 3.49; 95% CI, 2.14-5.85). During the same period, anal cancer
      rates were stable among men and women. CONCLUSIONS: Rates of AIN 3 increased in
      San Francisco during 2000 through 2009, in conjunction with an anal cytology
      screening program for high-risk groups, whereas rates of invasive anal cancer
      were unchanged. Continued surveillance is necessary to evaluate the impact of
      screening and human papillomavirus vaccination on the prevention of human
      papillomavirus-related AIN and anal cancer.

PMID- 23861092
TI  - Differential regulation of defense-related gene expression in response to red rot
      pathogen Colletotrichum falcatum infection in sugarcane.
AB  - Red rot is a serious disease of sugarcane caused by the fungus Colletotrichum
      falcatum imposing a considerable economic loss annually in all sugarcane
      producing countries. In this study, we analyzed the early resistance response of
      sugarcane to red rot fungus by comparing the differences between control and
      inoculated stalk tissues. Differential display reverse transcription polymerase
      chain reaction (DD-RT-PCR) was employed to identify altered expression of genes
      in disease-resistant cv Co 93009, in response to pathogen infection. DD-RT-PCR
      identified 300 differentially expressed transcripts of which 112 were selected
      for further analysis. Cloning and sequence analysis of the isolated cDNA
      fragments resulted in functional categorization of these clones into five
      categories, of which the defense/stress/signaling group was the largest, with
      clones homologous to genes known to be actively involved in various pathogenesis
      related functions in plant species. This group showed overexpression of several
      transcripts related to ethylene-mediated and jasmonic acid pathway of plant
      defense mechanisms. Of the 112 expressed sequence tags, validation of expression
      was carried out for five important genes whose role in plant defense mechanisms
      is well established. This is the first report of Colletotrichum-mediated gene
      regulation in sugarcane which has provided a set of candidate genes for detailed
      molecular dissection of signaling and defense responses in tropical sugarcane
      during the onset of red rot resistance. 

PMID- 23861090
TI  - The glial scar in spinal cord injury and repair.
AB  - Glial scarring following severe tissue damage and inflammation after spinal cord
      injury (SCI) is due to an extreme, uncontrolled form of reactive astrogliosis
      that typically occurs around the injury site. The scarring process includes the
      misalignment of activated astrocytes and the deposition of inhibitory chondroitin
      sulfate proteoglycans. Here, we first discuss recent developments in the
      molecular and cellular features of glial scar formation, with special focus on
      the potential cellular origin of scar-forming cells and the molecular mechanisms
      underlying glial scar formation after SCI. Second, we discuss the role of glial
      scar formation in the regulation of axonal regeneration and the cascades of neuro
      inflammation. Last, we summarize the physical and pharmacological approaches
      targeting the modulation of glial scarring to better understand the role of glial
      scar formation in the repair of SCI. 

PMID- 23861093
TI  - Parent-therapist alliance in Family-Based Treatment for adolescents with anorexia
      nervosa.
AB  - OBJECTIVE: This study aimed to describe the role of parent alliance in Family
      Based Treatment (FBT) for adolescents with anorexia nervosa (AN). Differences
      between parent and child alliance with the therapist, mothers' and fathers'
      alliance, and their relationship to outcome were examined. METHOD: Independent
      observers rated audiotapes of early therapy sessions to assess the therapeutic
      alliance of parents and adolescents with AN in FBT. Outcome was defined using a
      previously established cut-point for recovery from AN. RESULTS: Mothers' and
      fathers' alliance scores with the therapist were similar and significantly higher
      than adolescent alliance scores early in treatment. Combined parent alliance did
      not predict recovery at the end of treatment. Difference in alliance scores
      between mothers and fathers, and parents and their child also did not predict
      recovery at the end of treatment. CONCLUSIONS: In FBT, parents developed a strong
      alliance with the therapist early in treatment. These scores were consistent with
      the focus in FBT on parental management of eating disorder symptoms, as was the
      fact that alliance between adolescents and therapists was lower. Although
      parental therapeutic alliance was likely important in FBT, its role in treatment
      response remains uncertain.

PMID- 23861094
TI  - Effectiveness of a workplace training programme in improving social,
      communication and emotional skills for adults with autism and intellectual
      disability in Hong Kong--a pilot study.
AB  - This pilot study explored the effectiveness of workplace training programme that
      aimed to enhance the work-related behaviours in individuals with autism and
      intellectual disabilities. Fourteen participants with autism and mild to moderate
      intellectual disability (mean age = 24.6 years) were recruited. The workplace
      training programme included practices in work context and group educational
      sessions. A pre-test-post-test design was used with the Work Personality Profile,
      the Scale of Independent Behaviour Revised and the Observational Emotional
      Inventory Revised to evaluate the targeted behaviours. Improvement in social and
      communication skills specific to the workplace was achieved. For emotional
      control, participants became less confused and had a better self-concept.
      However, improvement in other general emotional behaviours, such as impulse
      control, was limited. The results indicated that a structured workplace training
      programme aimed at improving social, communication and emotional behaviours can
      be helpful for people with autism and intellectual disability. Further study with
      a larger sample size and a control group is recommended. The development of
      specific programme to cater for the emotional control needs at workplace for
      people with autism is also suggested.

PMID- 23861096
TI  - Motion for debate: osteoarthritis clinical trials have not identified efficacious
      therapies because traditional imaging outcome measures are inadequate.

PMID- 23861097
TI  - Dating violence experiences of lesbian, gay, bisexual, and transgender youth.
AB  - Media attention and the literature on lesbian, gay, and bisexual youth
      overwhelmingly focus on violence involving hate crimes and bullying, while
      ignoring the fact that vulnerable youth also may be at increased risk of violence
      in their dating relationships. In this study, we examine physical, psychological,
      sexual, and cyber dating violence experiences among lesbian, gay, and bisexual
      youth--as compared to those of heterosexual youth, and we explore variations in
      the likelihood of help-seeking behavior and the presence of particular risk
      factors among both types of dating violence victims. A total of 5,647 youth (51 %
      female, 74 % White) from 10 schools participated in a cross-sectional anonymous
      survey, of which 3,745 reported currently being in a dating relationship or
      having been in one during the prior year. Results indicated that lesbian, gay,
      and bisexual youth are at higher risk for all types of dating violence
      victimization (and nearly all types of dating violence perpetration), compared to
      heterosexual youth. Further, when looking at gender identity, transgender and
      female youth are at highest risk of most types of victimization, and are the most
      likely perpetrators of all forms of dating violence but sexual coercion, which
      begs further exploration. The findings support the development of dating violence
      prevention programs that specifically target the needs and vulnerabilities of
      lesbian, gay, and bisexual youth, in addition to those of female and transgender
      youth.

PMID- 23861098
TI  - Tissue aluminum concentration does not affect the genomic stability of ERBB2, C
      MYC, and CCND1 genes in breast cancer.
AB  - It has long been hypothesized that body tissue uptake of aluminum may have
      biological implications in breast cancer. In vitro and in vivo studies have shown
      that aluminum may trigger genomic instability by interfering with DNA strands.
      The objective of this study was to examine the relationship between aluminum
      concentrations in the peripheral and central areas of breast tumors with the
      instability of three key genes in breast cancer, ERBB2, C-MYC, and CCND1 and
      aneuploidy of the chromosomes harboring these genes. Tissue samples of 118 women
      treated for breast cancer were obtained. Evaluation of aluminum content was
      carried out using graphite furnace atomic absorption spectrometry. A tissue
      microarray slide containing the tumor samples was used in FISH assays to assess
      ERBB2, C-MYC, and CCND1 expressions as well as the statuses of their respective
      chromosomes 17, 8, and 11. Clinicopathological data were obtained from patient's
      records. Aluminum levels of >2.0 mg/kg were found in 20.3 and 22.1% of the
      central and peripheral breast tumor areas, respectively. Amplification and/or
      aneuploid-positive statuses for ERBB2/CEP17, C-MYC/CEP8, and CCND1/CEP11 were
      detected in 24, 36.7, and 29.3% of the tumors, respectively. We found that
      aluminum concentration was not related to these altered gene statuses. Our
      findings suggest that aluminum concentration does not affect genomic stability in
      breast tissues. Tissue microenvironment modifications, due to the presence of
      aluminum compounds, seem more appealing as a possible target for future studies
      to determine the implications of aluminum in breast carcinogenesis.

PMID- 23861099
TI  - Correlation between endodontic broken instrument and nickel level in urine.
AB  - This study aims to evaluate the correlation between the presences of separated
      endodontic instrument inside the dental canal and the nickel (Ni) level in the
      urine samples of subjected patients. Same-gendered and near-aged participants
      were selected and were instructed to collect their urine in sterile nickel-free
      plastic containers. The procedures were carried out in the office, and samples
      were stored in low-temperature cooler for 1 day and then they were transferred to
      the laboratory for electrothermal atomic absorption spectrometry. The level of Ni
      was measured and the correlation coefficient was calculated. Data were analyzed
      using t tests, Pearson's correlation coefficients, and linear regression
      analysis, at a level of significance P < 0.05. The statistical analysis has
      showed significant difference in Ni level between endodontic and control groups
      (P < 0.05). There was no correlation between Ni level in urine and the age or
      time period of broken instrument inside the canal; however, Ni level of urine and
      the age of participants in experimental group has demonstrated a positive
      correlation. The amount of Ni element can be increased in the urine of patients
      who have experienced broken endodontic instrument inside the dental canal.
      However, there is no positive correlation between the remaining pieces of
      instruments inside the canal and the elevation of nickel amount in urine during
      the tested time period. This issue suggested that the aging of remaining broken
      instrument inside the canal does not show any remarkable concern regarding the Ni
      elevation in the urine excreted by an individual.

PMID- 23861102
TI  - Antioxidant and anticancer activity of 3,5-dihydroxy-4-isopropylstilbene produced
      by Bacillus sp. N strain isolated from entomopathogenic nematode.
AB  - 3,5-Dihydroxy-4-isopropylstilbene is a natural phytoalexin and was first
      identified as bacterial secondary metabolites. The aim of this study is to
      investigate in vitro antioxidant and anticancer activity of 3,5-dihydroxy-4
      isopropystilbene purified from the cell free culture filtrate of Bacillus sp. N
      strain associated with rhabditid entomopathogenic nematode. Antioxidant activity
      was evaluated by five separate methods: free radical scavenging, reducing power
      assay, chelating effects on ferrous ions, NBT superoxide radical scavenging assay
      and hydroxyl radical scavenging activity. The stilbene recorded powerful
      antioxidant activity at various antioxidant systems in vitro. The superoxide
      radical scavenging (92.1 %) and hydroxyl radical scavenging (83.4 %) activities
      of the stilbenes at 100 MUg/ml were higher than the butylated hydroxyanisole, the
      known antioxidant agent. Anticancer activity of stilbene was tested against
      breast cancer (MDAM B-231), cervical cancer (HeLa), lung cancer (A 549), colon
      cancer (HTL 116) cell lines using MTT method. The induction of apoptosis was
      studied by morphological analysis, apoptotic cell staining, caspase 3 activation
      assay and cell cycle analysis using flow cytometry. Stilbene induced significant
      morphological changes and DNA fragmentation associated with apoptosis in HeLa
      cells. Acridine orange/ethidium bromide stained cells indicated apoptosis
      induction by stilbene. Up-regulation of caspase 3 activity was also found in
      cells treated with stilbene. Flow cytometry analysis showed an increase in the
      percentage of apoptotic cells in sub G0 phase (2.4 % in control plates to 11.4 %
      in 25 MUg/ml of stilbene) confirming the stilbene induced apoptosis. The results
      of the present study showed that stilbene demonstrated a strong antioxidant and
      anticancer effects. These suggest that stilbene may be used as possible natural
      antioxidant and anticancer agents to control various human diseases.

PMID- 23861100
TI  - Distribution of genital wart human papillomavirus genotypes in China: a multi
      center study.
AB  - Although it is understood that low-risk human papillomavirus (HPV) genotypes are
      associated with genital warts, there have been very few published studies
      reporting the genotype-specific prevalence of HPV among Chinese population. The
      aim of the study was to assess the prevalence of HPV genotypes in genital warts
      across China, and thus to evaluate the potential benefit of a quadrivalent HPV
      vaccine in this population. The tissue samples of a total of 1,005 genital warts
      cases were collected from seven geographical regions of China. HPV genotypes were
      analyzed using the general primer PCR and sequence-based typing method.
      Prevalence differences between sexes, geographical regions and age groups were
      assessed. The overall prevalence of HPV DNA in genital warts patients was 88.7%
      (891/1,005). Low-risk genotypes predominated, with a prevalence of 78.1%
      (785/1,005). The most prevalent genotypes were HPV-6 (41.3%), HPV-11 (37.6%) and
      HPV-16 (10.4%). Among HPV positive patients, single infections were more frequent
      (866/891, 97.2%) than co-infections (25/891, 2.8%). Both the overall prevalence
      of HPV DNA and that of HPV-6/-11/-16 (positive for any of the three types)
      decreased with age (P-trend = 0.010 and P-trend = 0.025, respectively). The
      prevalence of HPV-6/-11 (positive for either HPV type) and HPV-16 varied by
      geographic region (P = 0.003 and P <= 0.001, respectively). The prevalence of HPV
      16 in female patients between urban and rural areas showed a marginally
      significant difference (P = 0.05). In sum, the results provide strong evidence
      that, in China, the most prevalent HPV genotypes in genital warts are HPV-6, HPV
      11 and HPV-16. This indicates that a quadrivalent HPV vaccine may decrease the
      incidence of genital warts in the future.

PMID- 23861104
TI  - Prevalence of type 2 diabetes in Argentina 1979-2012.
AB  - The objective of this review was to revise the existing information regarding
      type 2 diabetes (T2D) prevalence in the Argentine population during the past 30
      years and to see whether the available data and methodology of the studies
      conducted allow analysis of time trends. The PubMED and LILACS databases were
      searched using the search terms "diabetes prevalence" and "Argentina". A total of
      301 studies were identified and 19 of them remained in the review after applying
      the inclusion and exclusion criteria. The studies reviewed covered a time period
      of 30 years (1979-2012). The studies conducted in Argentina during the last 30
      years assessing the prevalence of T2D are very heterogeneous. The majority of the
      studies were conducted in the province of Buenos Aires. As the assessment of T2D
      varied between the studies in respect of diagnostic criteria and diagnostic tests
      for T2D, meaningful comparisons are difficult to make, not to mention an analysis
      of time trends. All in all, the T2D prevalence seems to be at least 10% in the
      Argentina population. However, the latest large population surveys conducted in
      Argentina is promising and may offer the most reliable estimates of the T2D
      prevalence even though the diagnosis of T2D was based on participant self-report.
      This article is protected by copyright. All rights reserved.

PMID- 23861103
TI  - Noggin resistance contributes to the potent osteogenic capability of BMP9 in
      mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitors and can differentiate
      into osteogenic, chondrogenic, and adipogenic lineages. Bone morphogenetic
      proteins (BMPs) play important roles in stem cell proliferation and
      differentiation. We recently demonstrated that BMP9 is a potent but less
      understood osteogenic factor. We previously found that BMP9-induced ectopic bone
      formation is not inhibited by BMP3. Here, we investigate the effect of BMP
      antagonist noggin on BMP9-induced osteogenic differentiation. BMP antagonists
      noggin, chording, gremlin, follistatin, and BMP3 are highly expressed in MSCs,
      while noggin and follistatin are lowly expressed in more differentiated pre
      osteoblast C2C12 cells. BMP9-induced osteogenic markers and matrix mineralization
      are not inhibited by noggin, while noggin blunts BMP2, BMP4, BMP6, and BMP7
      induced osteogenic markers and mineralization. Likewise, ectopic bone formation
      by MSCs transduced with BMP9, but not the other four BMPs, is resistant to noggin
      inhibition. BMP9-induced nuclear translocation of Smad1/5/8 is not affected by
      noggin, while noggin blocks BMP2-induced activation of Smad1/5/8 in MSCs. Noggin
      fails to inhibit BMP9-induced expression of downstream targets in MSCs. Thus, our
      results strongly suggest that BMP9 may effectively overcome noggin inhibition,
      which should at least in part contribute to BMP9's potent osteogenic capability
      in MSCs.

PMID- 23861105
TI  - Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome
      and its stability during disease progression.
AB  - We aimed to analyze clinical impacts of the U2AF1 mutation on patients with
      myelodysplastic syndrome (MDS) and its stability during disease progression. We
      checked mutation status of the U2AF1 by direct sequencing in 478 de novo MDS
      patients and correlated with the clinical characteristics and outcomes. We also
      sequentially analyzed the U2AF1 mutation in 421 samples from 142 patients to
      determine its stability during the disease courses. Thirty-six patients (7.5%)
      were found to have U2AF1 mutations, which occurred more frequently in younger
      patients (P = 0.033). U2AF1 mutation was an independent poor-risk factor for
      overall survival (OS) in all patients (P = 0.030) and younger patients (P =
      0.041). U2AF1 mutation could also predict shorter time-to-leukemia transformation
      (TTL) in younger patients (P = 0.020). In addition, U2AF1 mutation was associated
      with shorter TTL in lower-risk MDS patients. Sequential analyses showed all
      original U2AF1 mutations in U2AF1-mutated patients were retained during follow
      ups unless complete remission was achieved, whereas none of the U2AF1-wild
      patients acquired a novel mutation during disease evolution. U2AF1 mutation is
      more prevalent in younger MDS patients and associated with inferior outcomes
      although it is stable during the clinical course. The mutation may be used as a
      biomarker for risk stratification.

PMID- 23861106
TI  - Differential remodeling of cadherins and intermediate cytoskeletal filaments
      influence microenvironment of solid and ascitic sarcoma.
AB  - Different forms of sarcoma (solid or ascitic) often pose a critical medical
      situation for pediatric or adolescent group of patients. To date, predisposed
      genetic anomalies and related changes in protein expression are thought to be
      responsible for sarcoma development. However, in spite of genetic abnormality,
      role of tumor microenvironment is also indispensable for the evolving neoplasm.
      In our present study, we characterized the deferentially remodeled
      microenvironment in solid and ascitic tumors by sequential immunohistochemistry
      and flowcytometric analysis of E-cdaherin, N-cadherin, vimentin, and cytokeratin
      along with angiogenesis and metastasis. In addition, we considered flowcytometric
      apoptosis and CD133 positive cancer stem cell analysis. Comparative hemogram was
      also considered as a part. Our investigation revealed that both types of tumor
      promoted neovascularization over time with sign of local inflammation. Invasion
      of neighboring skeletal muscle by solid sarcoma was more frequent than its
      ascitic counterpart. In contrary, rapid and earlier cadherin switching (E
      cadherin to N-cadherin) in ascitic sarcoma made them more aggressive than that of
      solid sarcoma and helped to early metastasize distant tissue like liver through
      the hematogenous route. Differential cadherin switching and infidelity of
      cytokeratin expression in Vimentin positive sarcoma also influenced the behavior
      of ascitic CD133+ cancer initiating cell pool with respect to CD133+ cells housed
      in solid sarcoma. Therefore our study concludes that differential cadherin
      switching program and infidelity of intermediate filaments in part, sharply
      discriminate the severity and metastatic potentiality of either type of sarcoma
      accompanying with CD133+ cellular repertoire. Besides, tumor phenotype-based
      dichotomous cadherin switching program could be exploited as a future drug target
      to manage decompensated malignant ascitic and solid sarcoma. 

PMID- 23861109
TI  - Increased pulse wave velocity in patients with ulcerative colitis.

PMID- 23861108
TI  - Betaine protects against high-fat-diet-induced liver injury by inhibition of high
      mobility group box 1 and Toll-like receptor 4 expression in rats.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have shown that betaine prevents
      alcohol-induced liver injury and improves liver function. The purpose of this
      study was to investigate the hepatoprotective effects of betaine on nonalcoholic
      fatty liver disease (NAFLD) and to observe changes of HMGB1/TLR4 signaling.
      METHODS: Thirty rats were randomly divided into control, model, and betaine
      groups. The rats in the model and betaine groups were fed a high-fat diet for 12
      weeks to induce an animal model of NAFLD. The rats in the betaine group were then
      intragastrically administered betaine solution at a dose of 400 mg/kg per day for
      four weeks. Liver histology was examined. Serum levels of ALT, AST, TC, TG, HDL
      C, LDL-C, FFA, HMGB1, NF-kappaB, TLR4, and tHcy were determined and intrahepatic
      TC, TG, and Hcy levels were assayed. mRNA expression and protein levels of HMGB1,
      NF-kappaB, and TLR4 in liver tissue were also determined. RESULTS: Compared with
      the control group, rats in the model group developed severe liver injury,
      accompanied by significant increases in serum levels of ALT, AST, TC, TG, LDL-C,
      FFA, HMGB1, NF-kappaB, and TLR4, intrahepatic TC, TG, and Hcy content,
      histological scores for steatosis, inflammation, and necrosis, and mRNA
      expression and protein levels of HMGB1, NF-kappaB, and TLR4, and a significant
      decrease in serum HDL-C (P < 0.05). Compared with the model group, all these
      indicators were significantly improved by administration of betaine (P < 0.05).
      CONCLUSIONS: Betaine effectively protects against high-fat-diet-induced NAFLD and
      improves liver function; the mechanism is probably related to inhibition of
      HMGB1/TLR4 signaling pathways.

PMID- 23861110
TI  - A case of primary malignant melanoma of the esophagus.

PMID- 23861111
TI  - Percutaneous transhepatic treatment using retrievable covered stents in patients
      with benign biliary strictures: mid-term outcomes in 68 patients.
AB  - BACKGROUND: Percutaneous balloon dilation of benign biliary stricture has been
      the most widely used alternative to endoscopic treatment; however, the rate of
      recurrence has varied from 15 to 44 %. Recently, several investigators have
      reported that percutaneous transhepatic placement of retrievable covered stents
      is feasible for the treatment of benign biliary strictures. However, these
      studies had only a small number of patients and had short follow-up periods. AIM:
      The purpose of this study was to investigate the mid-term outcomes of a
      retrievable covered stent for treatment of benign biliary strictures. METHODS: We
      retrospectively assessed 68 patients who underwent percutaneous transhepatic
      placement and removal of a retrievable covered stent between March 2007 and
      November 2012, for treatment of benign biliary strictures. Forty-two patients had
      not previously undergone interventional treatment, whereas 26 had recurrent or
      refractory strictures despite previous percutaneous procedures. RESULTS:
      Placement of the retrievable covered stents was technically successful in all
      patients. Stent migration occurred in 11 (16.2 %) patients. The mean indwelling
      period of drainage catheter and stent were 5.8 months (range, 3-22.5 months) and
      3 months (range, 2-6.5 months), respectively. Clinical success was achieved in 59
      (86.8 %) patients. During the mean follow-up of 36 months (range, 8.5-65 months),
      12 (20 %) of 60 patients had recurrence of clinically significant strictures. The
      primary patency rates at 1, 2, 3, 4, and 5 years were 91, 89, 76, 68, and 68 %,
      respectively. CONCLUSION: Mid-term outcomes suggested that percutaneous treatment
      of benign biliary strictures using a retrievable covered stent was a clinically
      effective method.

PMID- 23861112
TI  - Covered self-expandable metal stents for the treatment of benign biliary
      strictures after liver transplantation: when and how?

PMID- 23861113
TI  - "Too hot" or "too cold": effects of meal temperature on gastric function.

PMID- 23861114
TI  - Clinical significance and long-term outcome of incidentally found bile duct
      dilatation.
AB  - BACKGROUND AND AIM: The significance of incidentally detected bile duct
      dilatation has not yet been elucidated and there are only a few studies on
      asymptomatic patients with a dilated bile duct. This study aimed to investigate
      the causes and natural course of bile duct dilatation in asymptomatic patients.
      METHODS: A retrospective review of medical records was conducted for individuals
      in whom bile duct dilatation was detected by routine screening abdominal
      ultrasound at a health promotion center in Samsung Medical Center from January
      2005 to April 2008. RESULTS: A total of 514 patients were included; the mean age
      was 60.1 +/- 9.9 and the median follow-up period was 72 (interquartile range 56
      85) months. Thirty-eight individuals who had a definite cause or biliary disease
      requiring treatment at the time of detection of bile duct dilatation were
      compared with 476 individuals who did not have a definitive cause or who did not
      need treatment. Both common bile duct (CBD) dilatation and intrahepatic bile duct
      (IHBD) dilatation were significantly related to the presence of a definitive
      causative lesion (OR 3.95; 95 % CI 1.77-8.82; p = 0.001). In the IHBD dilatation
      group, the severity of dilatation was also associated with the presence of a
      definitive causative lesion (OR 5.77; 95 % CI 1.32-25.26; p = 0.020). CONCLUSION:
      Incidentally found biliary dilatation could be a prodrome of significant biliary
      tree disease. Therefore, further evaluation and regular follow up should be
      considered especially for marked IHBD dilatation or concomitant dilatation of CBD
      and IHBD detected on ultrasound.

PMID- 23861117
TI  - Growing patient safety through ERM.

PMID- 23861115
TI  - The role of Fas expression on the occurrence of immunosuppression in severe acute
      pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis (SAP) is a dangerous illness with high
      mortality where most patients do not die of excessive inflammation, but die of
      immunosuppression and multiple infections at a later stage. The mechanism of
      immunosuppression in SAP is unknown. AIM: The purpose of this study was to
      analyze the role of Fas expression on the occurrence of immunosuppression in
      patients with SAP. METHODS: Forty-eight patients with pancreatitis were divided
      into two groups: 20 cases with SAP (7 cases with sepsis, 13 cases without sepsis)
      and 28 cases with mild acute pancreatitis (MAP). Twenty-eight healthy volunteers
      were selected as controls. Fas mRNA expression in peripheral blood was detected
      by qPCR and Fas protein of lymphocyte membranes; T lymphocyte subsets and
      expression of monocyte Human leukocyte antigen DR (HLA-DR) in peripheral blood
      were detected by flow cytometry. RESULTS: Compared with MAP and control groups,
      expression level of Fas mRNA and lymphocyte Fas protein in peripheral blood were
      significantly increased in the SAP group (all P < 0.01). There was a further
      significant increase in the SAP group with sepsis compared to those without
      sepsis (all P < 0.01). The CD4(+) T cell ratio, CD4(+)/CD8(+) ratio and monocyte
      HLA-DR expression in the SAP group were decreased significantly compared with MAP
      and control groups (all P < 0.01). Significant negative relationships were
      observed between Fas mRNA expression and CD4(+) T-cell ratio, CD4(+)/CD8(+)
      ratio, and monocyte HLA-DR expression in SAP patients with sepsis (all P < 0.05).
      CONCLUSIONS: The results suggest that expression level of Fas is related to
      severity and immune status of pancreatitis. Overexpression of Fas may lead to the
      occurrence of immunosuppression and sepsis.

PMID- 23861118
TI  - Communicate, don't litigate: The Schwartz Center Connections Program.
AB  - Little is known about effective educational approaches intended to reduce
      malpractice risk by improving communication with patients and among
      multidisciplinary teams in outpatient settings in order to prevent diagnostic
      delays and errors. This article discusses a prospective, controlled educational
      intervention that aimed to open lines of communication among teams in two
      disciplines: identifying how and why communication lapses occur between
      disciplines and with patients, and articulating strategies to avert them. 

PMID- 23861119
TI  - Automated, wireless, continuous, intelligent, and noninvasive systems for risk
      management and performance improvement in vital signs monitoring.
AB  - Few health professionals need to stay up-to-date on as many different problems
      and solutions as risk managers do. Consequently, a single solution that resolves
      several problems at once is really helpful for job performance, especially when
      it doesn't require duplicating effort in multiple areas. This article summarizes
      current literature about one such technology that helps risk managers address 3
      of today's biggest challenges for healthcare delivery organizations: reducing
      costs, improving quality, and preventing harm across the continuum of clinical
      care; ensuring valid and reliable data for healthcare clinical and managerial
      decision makers; and adopting technologies that improve the medical marketplace. 

PMID- 23861120
TI  - Why are autopsy rates low in Japan? Views of ordinary citizens and doctors in the
      case of unexpected patient death and medical error.
AB  - This article examines what could account for the low autopsy rate in Japan based
      on the findings from an anonymous, self-administered, structured questionnaire
      that was given to a sample population of the general public and physicians in
      Japan. The general public and physicians indicated that autopsy may not be
      carried out because: (1) conducting an autopsy might result in the accusation
      that patient death was caused by a medical error even when there was no error
      (50.4% vs. 13.1%, respectively), (2) suggesting an autopsy makes the families
      suspicious of a medical error even when there was none (61.0% vs. 19.1%,
      respectively), (3) families do not want the body to be damaged by autopsy (81.6%
      vs. 87.3%, respectively), and (4) families do not want to make the patient suffer
      any more in addition to what he/she has already endured (61.8% vs. 87.1%,
      respectively). 

PMID- 23861121
TI  - Sociocultural differences, medicolegal implications, and risk management issues
      in the medical care of an elderly Chinese woman.
AB  - Large urban hospitals and their physicians confronted with unanticipated
      admissions involving international patients may often experience cross-cultural
      conflicts arising in the course of a patient's medical care. Conflicts of this
      nature can place the healthcare team, the patient, and the family at odds due to
      their respective traditions and the laws, regulations, and guidelines upheld and
      followed in the United States. The following is a complicated case illustrating a
      variety of legal, ethical, and clinical issues for Patient XX, an international
      patient emergently presenting to a large US medical health system for diagnosis
      and treatment. 

PMID- 23861122
TI  - Anticoagulant medication errors in nursing homes: characteristics, causes,
      outcomes, and association with patient harm.
AB  - Appropriate and safe use of medications is an important aspect of quality of care
      in nursing home patients. Because of their complex medication use process,
      anticoagulants are prone to medication errors in the frail elderly. Therefore, we
      designed this study to characterize anticoagulant medication errors and to
      evaluate their association with patient harm using individual medication error
      incidents reported by all North Carolina nursing homes to the Medication Error
      Quality Initiative (MEQI) during fiscal years 2010-2011. Characteristics, causes,
      and specific outcomes of harmful anticoagulant medication errors were reported as
      frequencies and proportions and compared between anticoagulant errors and other
      medication errors using chi-square tests. A multivariate logistic regression
      model explored the relationship between anticoagulant medication errors and
      patient harm, controlling for patient- and error-related factors. 

PMID- 23861123
TI  - Healthcare risk management challenges created by federal regulation of electronic
      medical records and care management.
AB  - Health information technology (HIT) continues to evolve at an ever accelerating
      pace. Recent federal legislation has encouraged the widespread adoption of
      electronic record systems in the healthcare environment.(1) The federal
      government recognizes that advanced electronic health record (EHR) systems with
      clinical decision support (CDS) functionalities have the potential to offer
      numerous benefits to the quality of patient care.(2.) 

PMID- 23861124
TI  - Case law update. Legal liability in emergency medicine and risk management
      considerations.

PMID- 23861125
TI  - Right hand knob infarction.

PMID- 23861126
TI  - Evidence for two phylogenetic clusters within hepatitis C virus (HCV) genotype 2
      inferred from analysis of complete coding sequences of 15 HCV strains.
AB  - The aim of this study was to gain further insight into the evolution and
      classification of hepatitis C virus (HCV) by assessing the subtype distribution
      of 273 genotype 2 strains isolated from French blood donors from 1990 to 2010 and
      by determining complete coding sequences in subtype 2 strains. These classified
      into 7 of the established subtypes and into 15 additional lineages not yet
      assigned to a known subtype. Phylogenetic tree construction showed two well
      supported clusters. Cluster 1 included most subtype 2 strains while cluster 2
      included subtype 2l and one unassigned subtype 2. Full genome sequencing was
      performed on 15 genotype 2 strains belonging to both clusters, that is, one
      subtype 2b, two subtype 2c, three subtype 2i, two subtype 2j, one subtype 2k, two
      subtype 2l, and four unassigned strains. Genomes included a 9042- to 9108-nucleic
      acid open reading frame coding for a polyprotein comprising 3014-3036 amino
      acids. Mean nucleotide distances between subtypes belonging to the first cluster
      was 20.2 +/- 1.4% while the mean distance between the two clusters was 25.9 +/-
      0.3%. Analysis indicated that the bifurcation between subtype 2l and other
      subtype 2 strains occurred early in the evolutionary process. Subtype 2l retained
      a genomic feature characteristic of non-genotype 2, that is, absence of the 60
      nucleotide insertion in the NS5A region. This finding suggests that appearance
      and fixation of this insertion occurred late in the evolutionary history of HCV
      type 2 and that its absence is an ancestral feature of HCV.

PMID- 23861127
TI  - Transcatheter closure of a large patent ductus arteriosus with severe pulmonary
      arterial hypertension in a child.

PMID- 23861128
TI  - Intravenous leiomyomatosis extending to the heart: a multimodality imaging
      approach.

PMID- 23861129
TI  - Percutaneous edge-to-edge mitral valve repair. Current clinical evidence with the
      MitraClip System.
AB  - In the past few years, a myriad of technologies have been developed for
      percutaneous repair of the mitral valve for patients with severe mitral
      regurgitation (MR) and at high risk for traditional open-heart mitral valve
      surgery. Among them, MitraClip has emerged as the only clinically safe and
      effective method for percutaneous mitral valve repair. This device mimics the
      surgical edge-to-edge mitral valve repair initially described by Dr. Alfieri. In
      this article, we review the current clinical evidence on the use of the MitraClip
      -from the randomized control trial EVEREST II to the information derived from
      expert high-volume centers.

PMID- 23861131
TI  - Huge leiomyosarcoma in the left atrium.

PMID- 23861130
TI  - A single coronary artery with a right ventricular fistula: unique therapy with
      covered-stent implantation.

PMID- 23861132
TI  - The role of bilirubin and its protective function against coronary heart disease.
AB  - BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of
      morbidity and mortality both in industrialized and developing countries.
      Atherosclerosis is a chronic inflammatory disease of the arterial wall, which
      also involves deposition and peroxidation of lipids. Bilirubin, an important
      endogenous antioxidant, may limit lipid peroxidation and retard the progression
      of atherosclerosis. Previous studies have reported an inverse relationship
      between serum bilirubin levels and the risk of coronary artery disease (CAD).
      Taking into account that atherosclerosis is a complex process that is initiated
      and accelerated by diverse risk factors, we aimed to test the antiatherosclerotic
      effects of bilirubin in a population with multiple risk factors for CAD. METHODS:
      The study included 221 patients who underwent coronary angiography owing to
      symptoms suggestive of ischemia and/or positive noninvasive stress test results.
      Of the patients, 76 had normal coronary angiograms and served as the control
      group. The remaining 145 patients with documented CAD and two or more
      cardiovascular risk factors constituted the study group. The study group (n=145)
      was further classified according to the Gensini score as follows: group 1 if
      Gensini score was 1-19 (minimal CAD, n=82), and group 2 if Gensini score was 20
      or higher (significant CAD, n=63). Biochemical assessments including total and
      direct serum bilirubin levels were carried out using standard methods in
      automated systems. RESULTS: All of the cardiovascular risk factors were found
      significantly more frequently in the study group (groups 1 and 2) than in the
      control group. Total and direct serum bilirubin levels did not differ
      significantly between the control group, group 1, and group 2. There was a
      moderate and significant positive correlation between direct bilirubin levels and
      the Gensini score (r = 0.158, p = 0.019). There was no significant correlation
      between total bilirubin levels and the Gensini score. CONCLUSION: In conclusion,
      our findings suggest that in the presence of multiple risk factors, similar
      concentrations of serum bilirubin may not confer the same level of protection
      against CAD as in an individual with a more favorable risk profile. The
      relationship between direct bilirubin levels and the Gensini score is unlikely to
      be causative, given the established antiatherosclerotic effects of bilirubin.

PMID- 23861133
TI  - Dilated cardiomyopathy in a postpartum hypocalcemic patient.

PMID- 23861134
TI  - Noninvasive assessment of subclinical atherosclerosis in normotensive gravidae
      with gestational diabetes.
AB  - AIM: Carotid artery intima-media thickness (CIMT), hyperhomocysteinemia,
      microalbuminuria, and nitric oxide reflect subclinical atherosclerosis and
      predict the risk of future cardiovascular events. We aimed to evaluate the
      presence of subclinical atherosclerosis and endothelial dysfunction in
      normotensive patients with gestational diabetes mellitus (GDM) noninvasively.
      PATIENTS AND METHODS: We enrolled 41 normotensive patients with GDM and 44
      healthy gravidae in the study. Serum homocysteine and nitric oxide levels,
      urinary albumin excretion (microalbuminuria), and CIMT were evaluated along with
      lipid parameters and anthropometric measurements. RESULTS: Patients with GDM had
      significantly higher levels of serum homocysteine, urinary albumin excretion, and
      increased CIMT (p < 0.001, p=0.005, and p < 0.001, respectively). Nitric oxide
      levels were significantly reduced in the patient group (p < 0.001). There was a
      significant difference between groups in terms of low-density lipoprotein (LDL)
      but not of high-density lipoprotein (HDL) and triglyceride levels. A significant
      correlation was observed between CIMT and serum LDL, HDL, homocysteine, nitric
      oxide levels, and urinary albumin excretion. Microalbuminuria was significantly
      correlated with serum homocysteine levels (p=0.03) but not with nitric oxide.
      CONCLUSION: Independent of elevated blood pressure, subclinical atherosclerosis
      and endothelial dysfunction exist in normotensive patients with GDM. Further
      studies with a large number of participants are required to clarify these data.

PMID- 23861136
TI  - Studies on correlation between single-nucleotide polymorphisms of tumor necrosis
      factor gene and different stages of ankylosing spondylitis.
AB  - To examine if there is any correlation between ankylosing spondylitis (AS) and
      TNF-alpha gene promoter single-nucleotide polymorphisms (SNP) and their
      associated haplotypes. Using restriction fragment length polymorphism-polymerase
      chain reaction method, the polymorphism of TNF-alpha-238, -308, -850, -857, -863
      locus, and TNF-beta +252 were analyzed in patients with progressive AS, stable AS
      and control. (1) Neither the genotypes nor the allele frequencies of TNF-alpha (
      308), (-238), (-863), and TNF-beta +252 showed differences in each group. TNF
      alpha (-850) CC genotype and C allele frequency distribution was significantly
      higher in healthy controls group than in the stable and progressive groups. TNF
      alpha (-857) CT, CC genotype, and C, T allele frequency showed differences in all
      groups. (2) Polymorphism linkage equilibrium test revealed that association of
      six TNF-alpha, beta gene SNPs with haplotype GACTCG in progressive group is
      significantly higher than in the stable group and healthy control group (P <
      0.05). TNF-alpha (-857), (-850) gene polymorphism may increase the susceptibility
      to AS, but do not reflect the disease active state. The CC genotype and C allele
      may play a protective role in the pathogenesis of AS. TNF-alpha (-308) may be a
      weak indicator reflecting the active state of AS. Haplotype GACTCG may indicate
      both the susceptibility and the activity of AS.

PMID- 23861135
TI  - Transthoracic echocardiographic and cardiopulmonary exercise testing parameters
      in Eisenmenger's syndrome. Association with six-minute walk test distance.
AB  - OBJECTIVE: The six-minute walk test (6MWT) evaluates the functional exercise
      capacity in patients with cardiopulmonary disease. We aimed to investigate the
      association between 6MWT distance and transthoracic echocardiographic (TTE)
      findings as well as cardiopulmonary exercise testing (CPET) parameters in
      Eisenmenger's syndrome (ES) patients waiting for heart-lung transplantation on
      their initial admission to our center. PATIENTS AND METHODS: A total of 23
      patients with ES (12 women, 11 men; mean age, 28.2 +/- 8.1 years) were included
      in the study. The correlation between 6MWT distance and CPET and TTE findings was
      retrospectively analyzed. RESULTS: The most frequent underlying heart diseases
      were ventricular septal defect (VSD) with complex congenital heart disease (n =
      10, 43 %) and isolated VSD (n = 7, 30 %). The 6MWT distance was 349.7 +/- 77.4 m
      in the study group. An inverse correlation was found between 6MWT distance and
      systolic pulmonary arterial pressure (SPAP) measured with TTE (r = - 0.445; p =
      0.03). All patients underwent CPET at the first visit. Mean VO2 max was 14.9 +/-
      3.3 ml/kg/min and the VE/VCO2 rate was 50.4 +/- 9.2 %. No significant correlation
      was observed between 6MWT and CPET findings. SPAP, which did not display any
      correlation with CPET findings, was the only independent predictor of 6MWT
      distance. CONCLUSION: We suggest that 6MWT distance may be more suitable than
      CPET in the follow-up of ES patients. Further prospective, randomized, controlled
      trials are necessary to make more robust interpretations of this issue.

PMID- 23861137
TI  - Prognostic impact of the activation status of the Akt/mTOR pathway in synovial
      sarcoma.
AB  - BACKGROUND: The Akt/mammalian target of rapamycin (mTOR) pathway, downstream from
      phosphatidylinositol 3-kinase (PI3K), mediates cell survival and proliferation.
      Although this pathway reportedly contributes to the progression of synovial
      sarcoma, its prognostic impact has not been clarified. METHODS: The authors
      analyzed clinicopathologic data and phosphorylation status of Akt (a
      serine/threonine kinase also known as protein kinase B), mTOR, the eukaryotic
      translation initiation factor 4E binding protein (4E-BP1), and the S6 ribosomal
      protein by immunohistochemical analysis of 120 formalin-fixed, paraffin-embedded
      samples and by Western blot analysis of 24 frozen samples from 112 patients with
      synovial sarcoma. RESULTS: Akt, mTOR, 4E-BP1, and S6 were activated in 76.5%,
      67.6%, 59.6%, and 42.6% of samples, respectively. Immunohistochemically positive
      phosphorylated (p) mTOR (pmTOR) and p4E-BP1 results were correlated with higher
      mitotic activity, and positive p4E-BP1 results were correlated with greater
      necrosis. No mutations around the hot spots in the PI3K catalytic subunit alpha
      (PI3KCA) and Akt1 genes were observed. In multivariate analysis of
      clinicopathologic parameters, frequent mitosis was a risk factor for shorter
      overall survival; and male sex, visceral location, larger tumor size, and
      frequent mitosis were identified as risk factors for shorter event-free survival.
      Positive pmTOR and p4E-BP1 results were correlated significantly with shorter
      overall survival, and positive p4E-BP1 results were correlated with shorter event
      free survival in univariate analysis. Positive pAkt results were associated
      significantly with shorter event-free survival in multivariate analysis.
      CONCLUSIONS: In this study, the Akt/mTOR pathway was activated and was associated
      with worse clinical and pathologic behavior in patients with synovial sarcoma.
      The authors propose that this pathway may have potential as a therapeutic target.

PMID- 23861138
TI  - Concurrent detection of other respiratory viruses in children shedding viable
      human respiratory syncytial virus.
AB  - Human respiratory syncytial virus (HRSV) is an important cause of respiratory
      disease. The majority of studies addressing the importance of virus co-infections
      to the HRSV-disease have been based on the detection of HRSV by RT-PCR, which may
      not distinguish current replication from prolonged shedding of remnant RNA from
      previous HRSV infections. To assess whether co-detections of other common
      respiratory viruses are associated with increased severity of HRSV illnesses from
      patients who were shedding viable-HRSV, nasopharyngeal aspirates from children
      younger than 5 years who sought medical care for respiratory infections in
      Ribeirao Preto (Brazil) were tested for HRSV by immunofluorescence, RT-PCR and
      virus isolation in cell culture. All samples with viable-HRSV were tested further
      by PCR for other respiratory viruses. HRSV-disease severity was assessed by a
      clinical score scale. A total of 266 samples from 247 children were collected and
      111 (42%) were HRSV-positive. HRSV was isolated from 70 (63%), and 52 (74%) of
      them were positive for at least one additional virus. HRSV-positive diseases were
      more severe than HRSV-negative ones, but there was no difference in disease
      severity between patients with viable-HRSV and those HRSV-positives by RT-PCR. Co
      detection of other viruses did not correlate with increased disease severity.
      HRSV isolation in cell culture does not seem to be superior to RT-PCR to
      distinguish infections associated with HRSV replication in studies of clinical
      impact of HRSV. A high rate of co-detection of other respiratory viruses was
      found in samples with viable-HRSV, but this was not associated with more severe
      HRSV infection.

PMID- 23861139
TI  - Attitudes of Australian chiropractic students toward whole body donation: a cross
      sectional study.
AB  - Cadavers play an important role in anatomy education. In Australia, bodies for
      anatomy education are acquired only through donations. To gain insight into
      educational dynamics in an anatomy laboratory as well as to facilitate body
      donation programs and thanksgiving ceremonies, it is important to understand
      students' attitudes toward body donation. In this cross-sectional study, the
      attitudes of Macquarie University's first, second, and fifth year chiropractic
      students toward body donation were investigated. Macquarie University
      chiropractic students have a four semester long anatomy program, which includes
      cadaver-based instruction on prosected specimens. A questionnaire was used to
      record respondents' demographics and attitudes toward body donation: personal, by
      a relative, and by a stranger. It was found that ethnicity and religion affect
      attitudes toward body donation, with Australian students being more willing to
      donate a stranger's body and atheists and agnostics being more willing to donate
      in general. Furthermore, willingness to donate one's own or a family member's
      body decreases as year of study increases, suggesting a possible negative impact
      of exposure to cadavers in the anatomy laboratory. This was only true, however,
      after controlling for age. Thus, the impact of viewing and handling prosected
      specimens, which is the norm in anatomy classes in Australia, may not be as
      strong as dissecting cadavers. It is suggested that anatomists and educators
      prepare students for cadaver-based instruction as well as exhibit sensitivity to
      cultural differences in how students approach working with cadavers, when
      informing different communities about body donation programs and in devising
      thanksgiving ceremonies.

PMID- 23861140
TI  - Infection risk after orthopedic surgery in patients with inflammatory rheumatic
      diseases treated with immunosuppressive drugs.
AB  - OBJECTIVE: The influence of specific medications on the risk of postoperative
      infection in patients with rheumatoid arthritis and other inflammatory rheumatic
      diseases (IRDs) remains unclear. This retrospective study examined the risk of
      postoperative infection at the site of surgery in patients treated with
      immunosuppressive drugs (including biologic agents) undergoing different types of
      orthopedic surgery. METHODS: The study included 50,359 cases of orthopedic
      surgery performed in our hospital between 2000 and 2008. The primary outcome was
      operation-related infection. IRD patients were compared with those with
      degenerative or posttraumatic disorders, and in IRD patients, the effect of
      immunosuppressive medication, specifically tumor necrosis factor alpha (TNFalpha)
      inhibitors and their preoperative management, was examined. RESULTS: There were
      373 operation-related infections (0.8%) of 47,887 cases in the
      degenerative/posttraumatic group and 49 (2.0%) of 2,472 in the IRD group (higher
      infection rate in the IRD group; odds ratio [OR] 2.58 [95% confidence interval
      (95% CI) 1.91-3.48], P < 0.001). In the IRD group, elbow and foot surgery had the
      highest infection rates. The risk of infection was significantly increased in
      patients taking multiple conventional disease-modifying antirheumatic drugs
      (DMARDs; OR 2.49 [95% CI 1.06-5.84], P = 0.036) or TNFalpha inhibitors (OR 2.54
      [95% CI 1.08-5.97], P = 0.032). The risk was especially high (6 [12%] of 49) if
      the last dose of TNFalpha inhibitor was given <1 administration interval before
      surgery. CONCLUSION: The risk of postoperative infection was elevated in patients
      with IRDs, especially those taking >1 conventional DMARD or TNFalpha inhibitors.
      It may be advisable to consider stopping TNFalpha inhibitors >=1 administration
      interval before surgery, since the risk of postoperative infection appears to be
      higher if the operation occurs within this period.

PMID- 23861141
TI  - Molecular epidemiology of rubella viruses involved in congenital rubella
      infections in Sao Paulo, Brazil, between 1996 and 2009.
AB  - Rubella virus (RV) infection during the early stages of pregnancy can lead to
      serious birth defects, known as congenital rubella syndrome (CRS). This
      retrospective study was conducted between 1996 and 2009 with surveillance
      specimens collected from patients suspected of congenital rubella infection (CRI)
      and CRS. The clinical samples (nine amminiotic fluid, eight urine, eight blood,
      one conception product, and one placenta) were sent for viral isolation and
      genotyping. Twenty-seven sequences were analysed and four genotypes (1a, 1B, 1G,
      and 2B) were identified in Sao Paulo that were involved in congenital infection.
      To our knowledge, this study is the first report that describes genetic diversity
      of the circulating rubella strains involved in CRI.

PMID- 23861142
TI  - Smad-interacting protein 1 affects acute and tonic, but not chronic pain.
AB  - BACKGROUND: Smad-interacting protein 1 (also named Zeb2 and Zfhx1b) is a
      transcription factor that plays an important role in neuronal development and,
      when mutated, causes Mowat-Wilson syndrome (MWS). A corresponding mouse model
      carrying a heterozygous Zeb2 deletion was comprehensively analysed in the German
      Mouse Clinic. The most prominent phenotype was the reduced pain sensitivity. In
      this study, we investigated the role of Zeb2 in inflammatory and neuropathic
      pain. METHODS: For this, we tested mutant Zeb2 animals in different models of
      inflammatory pain like abdominal constriction, formalin and carrageenan test.
      Furthermore, we studied the pain reactivity of the mice after peripheral nerve
      ligation. To examine the nociceptive transmission of primary sensory dorsal root
      ganglia (DRG) neurons, we determined the neuronal activity in the spinal dorsal
      horn after the formalin test using staining of c-Fos. Next, we characterized the
      neuronal cell population in the DRGs and in the sciatic nerve to study the effect
      of the Zeb2 mutation on peripheral nerve morphology. RESULTS: The present data
      show that Zeb2 is involved in the development of primary sensory DRG neurons,
      especially of C- and Adelta fibres. These alterations contribute to a hypoalgesic
      phenotype in inflammatory but not in neuropathic pain in these Zeb2(+/-) mice.
      CONCLUSION: Our data suggest that the under-reaction to pain observed in MWS
      patients results from a reduced responsivity to nociceptive stimulation rather
      than an inability to communicate discomfort.

PMID- 23861143
TI  - GPU-accelerated molecular mechanics computations.
AB  - In this article, we describe an improved cell-list approach designed to match the
      Kepler architecture of General-purpose graphics processing units (GPGPU). We
      explain how our approach improves load balancing for the above algorithm and how
      warp intrinsics are used to implement Newton's third law for the nonbonded force
      calculations. We also talk through our approach to exclusions handling together
      with a method to calculate bonded forces and 1-4 electrostatic scaling using a
      single Cuda kernel. Performance benchmarks are included in the last sections to
      show the linear scaling of our implementation using a step minimization method.
      In addition, multiple performance benchmarks demonstrate the contribution of
      various optimizations we used for our implementations. (c) 2013 Wiley
      Periodicals, Inc. 

PMID- 23861144
TI  - Mimivirus is not a frequent cause of ventilator-associated pneumonia in
      critically ill patients.
AB  - Acanthamoeba polyphaga mimivirus (APMV) belongs to the amoebae-associated
      microorganisms. Antibodies to APMV have been found in patients with pneumonia
      suggesting a potential role as a respiratory pathogen. In addition, positive
      serology for APMV was associated with an increased duration of mechanical
      ventilation and intensive care unit stay in patients with ventilator-associated
      pneumonia. The aim of the present study was to assess the presence of APMV in
      bronchoalveolar lavage fluid samples of critically ill patients suspected of
      ventilator-associated pneumonia. The study was conducted in the intensive care
      unit of the Maastricht University Medical Centre. All consecutive bronchoalveolar
      lavage fluid samples obtained between January 2005 and October 2009 from patients
      suspected of ventilator-associated pneumonia were eligible for inclusion. All
      samples were analyzed by real-time PCR targeting the APMV. A total of 260
      bronchoalveolar lavage fluid samples from 214 patients (139 male, 75 female) were
      included. Bacterial ventilator-associated pneumonia was confirmed
      microbiologically in 105 out of 260 (40%) suspected episodes of ventilator
      associated pneumonia (86 patients). The presence of APMV DNA could not be
      demonstrated in the bacterial ventilator-associated pneumonia positive or in the
      bacterial ventilator-associated pneumonia negative bronchoalveolar lavage fluid
      samples. Although suspected, APMV appeared not to be present in critically ill
      patients suspected of ventilator-associated pneumonia, and APMV does not seem to
      be a frequent cause of ventilator-associated pneumonia.

PMID- 23861146
TI  - Varying accuracy of myocardial perfusion SPECT and perfusion cardiac MRI for the
      detection of critical LMS coronary disease.

PMID- 23861147
TI  - Comparative study of nickel resistance of pure culture and co-culture of
      Acidithiobacillus thiooxidans and Leptospirillum ferriphilum.
AB  - The effect of Ni2+ on the growth and functional gene expression of the pure
      culture and co-culture of Acidithiobacillus thiooxidans and Leptospirillum
      ferriphilum has been studied. Compared with the pure culture, the co-culture
      showed a stronger sulfur and ferrous ion oxidation activity. At 100 mM, A.
      thiooxidans in co-culture grew faster and had 48 h shorter lag phases. The cell
      number of A. thiooxidans in co-culture was about 5 times higher than that in pure
      culture. The existence of A. thiooxidans in co-culture activated the expression
      of some metal resistance genes in L. ferriphilum at least 16 h in advance. A.
      thiooxidans in co-culture tends to chose more efficient pathways to transport
      nickel ion, ensuring the export of heavy metal was faster and more effective than
      that in pure culture. All the data indicated that there were synergetic
      interactions between iron- and sulfur-oxidizing bacteria under the stress of
      Ni2+.

PMID- 23861145
TI  - Birthdating of myenteric neuron subtypes in the small intestine of the mouse.
AB  - There are many different types of enteric neurons. Previous studies have
      identified the time at which some enteric neuron subtypes are born (exit the cell
      cycle) in the mouse, but the birthdates of some major enteric neuron subtypes are
      still incompletely characterized or unknown. We combined 5-ethynynl-2'
      deoxyuridine (EdU) labeling with antibody markers that identify myenteric neuron
      subtypes to determine when neuron subtypes are born in the mouse small intestine.
      We found that different neurochemical classes of enteric neuron differed in their
      birthdates; serotonin neurons were born first with peak cell cycle exit at E11.5,
      followed by neurofilament-M neurons, calcitonin gene-related peptide neurons
      (peak cell cycle exit for both at embryonic day [E]12.5-E13.5), tyrosine
      hydroxylase neurons (E15.5), nitric oxide synthase 1 (NOS1) neurons (E15.5), and
      calretinin neurons (postnatal day [P]0). The vast majority of myenteric neurons
      had exited the cell cycle by P10. We did not observe any EdU+/NOS1+ myenteric
      neurons in the small intestine of adult mice following EdU injection at E10.5 or
      E11.5, which was unexpected, as previous studies have shown that NOS1 neurons are
      present in E11.5 mice. Studies using the proliferation marker Ki67 revealed that
      very few NOS1 neurons in the E11.5 and E12.5 gut were proliferating. However, Cre
      lox-based genetic fate-mapping revealed a small subpopulation of myenteric
      neurons that appears to express NOS1 only transiently. Together, our results
      confirm a relationship between enteric neuron subtype and birthdate, and suggest
      that some enteric neurons exhibit neurochemical phenotypes during development
      that are different from their mature phenotype.

PMID- 23861148
TI  - Genetic and functional diversity among root-associated psychrotrophic
      Pseudomonad's isolated from the Himalayan plants.
AB  - Out of 534 psychrotrophic bacteria, 12 bacteria were selected on the basis of
      plant growth promoting activities at 4  degrees C and identified as Pseudomonas
      genus. These strains showed high level of genetic polymorphisms based on RAPD and
      rep-PCR fingerprinting. This genetic variability revealed that isolates belonging
      to same species were as high as the variability among different species. Further
      inoculation of these Pseudomonas strains significantly improves root/shoot
      biomass and nutrients uptake of lentil plant as compared to non-bacterized
      control after 40 days of seed showing. Agglomerative hierarchical clustering
      analysis of pot assay results revealed that genetically diverse strains showing
      the same prototype in functional parameter and representing diverse blueprint of
      plant growth promoting attributes. Results of present findings explain the huge
      beneficial microbial resources from root zone of hilly crops of Himalayan region
      that could be effectively exploited as bio-inoculums for cold climatic condition.

PMID- 23861149
TI  - The tyrosine recombinase MrpA and its target sequence: a mutational analysis of
      the recombination site mrpS resulting in a new left element/right element (LE/RE)
      deletion system.
AB  - MrpA is the multimer resolution protein of the Streptomyces coelicolor A3(2)
      plasmid SCP2*. Previously, MrpA was found to be a site-specific tyrosine
      recombinase that acts with the 36-bp recombination site mrpS. The present report
      gives a comprehensive characterization of the composition as well as the position
      of the spacer and MrpA binding sites within mrpS. Experiments revealed a spacer
      consisting of 6 remarkably variable nucleotides in the middle of the mrpS-site. A
      reduction in the spacer to 5 nucleotides abolished recombination. Investigation
      of the MrpA binding sites showed the importance of its 15 nucleotides on an
      effective recombination. Among almost randomly exchangeable nucleotides, two
      nucleotides were identified as essential for MrpA binding. Alteration of either
      of these nucleotides led to a reduction in MrpA binding down to 2 % or even to no
      binding. Based on these results, a new left element/right element (LE/RE)
      deletion system was developed. The constructed heteromeric mrpS-sites are
      efficiently resolved by MrpA. The resulting double mutated (LE/RE) site can no
      longer be used as a recombination site by MrpA. The system has been successfully
      applied for the generation of multiple-targeted deletions in the genome of E.
      coli. 

PMID- 23861150
TI  - Fluorescent epibiotic microbial community on the carapace of a Bahamian ostracod.
AB  - Ostracods collected from shallow coral reefs in the Bahamas were found to exhibit
      blue light-stimulated orange fluorescence at night. Fluorescent spectra revealed
      the presence of orange fluorescence with a maximum emission at ~595 nm on the
      carapace of these ostracods, while scanning electron microscopy revealed a
      morphologically diverse microbial community covering the entire carapace of these
      ostracods. Pyrosequencing and cyanobacterial-specific 16S rRNA sequencing reveals
      that this epibiont community is highly diverse and highly variable between
      individual ostracods. Many species of Cyanobacteria in the orders Oscillatoriales
      and Chroococcales, as well as other Proteobacteria and diatom chloroplast
      sequences, were identified using the cyanobacterial-specific primers. While no
      fluorescent proteins or phycoerythrin were detected in these ostracods, it is
      possible that the observed orange fluorescence is the result of carotenoid
      fluorescence from Cyanobacteria. The microbial consortium forms an epibiotic
      biofilm on the carapace of these ostracods whose functions are unknown. 

PMID- 23861151
TI  - Aspirin desensitization for aspirin-exacerbated respiratory disease (Samter's
      Triad): a systematic review of the literature.
AB  - OBJECTIVES: To critically review the current literature regarding aspirin
      desensitization treatment for nasal polyposis in patients with Aspirin
      Exacerbated Respiratory Disease (AERD). STUDY DESIGN: Systematic review of the
      literature. METHODS: All English literature published between January 1995 and
      February 2013 reporting specifically nasal outcomes following aspirin
      desensitization in AERD patients were eligible for inclusion. Exclusion criteria
      were non-investigative, non-human, and ex-vivo studies. Studies were categorized
      by level of evidence and evaluated for quality using the Downs and Black scale.
      RESULTS: A total of 614 citations were retrieved and eleven studies met the
      criteria for analysis. Outcome measurements included self-reported symptom
      scores, amount of corticosteroid use, rate of revision surgery, and quantitative
      measurements such as rhinomanometry. Overall, most studies reported a significant
      improvement in symptom scores, decrease in corticosteroid use, and decrease in
      revision surgery. A few studies showed promising results with quantitative
      outcomes. However, most studies were of Level 2 evidence with small samples
      sizes. Rates of adverse events ranged from 12.5% to 23%. CONCLUSIONS: Unlike
      traditional treatments for nasal polyposis, aspirin desensitization targets AERD
      etiology rather than phenotype and can be an effective therapeutic option. While
      the current literature shows encouraging results, additional studies are needed
      to better define clinical benefits.

PMID- 23861152
TI  - Fibroblast growth factor 2 is of prognostic value for patients with locally
      advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND AND PURPOSE: Patients with locally advanced SCCHN have a poor
      prognosis. This study investigated the prognostic value of the tumor cell
      expression of the fibroblast growth factor 2 (FGF-2) in patients treated with
      surgery followed by radiotherapy. PATIENTS AND METHODS: The impact of FGF-2
      expression and 11 additional potential prognostic factors on loco-regional
      control (LRC), metastases-free survival (MFS), and overall survival (OS) was
      retrospectively evaluated in 146 patients. Additional factors included age,
      gender, performance status, pre-radiotherapy hemoglobin levels, tumor site,
      histologic grade, T-category, N-category, human papilloma virus (HPV) status,
      extent of resection, and chemotherapy. Univariate analyses were performed with
      the Kaplan-Meier method and the log-rank test, multivariate analyses with the Cox
      proportional hazard model. RESULTS: On multivariate analysis, improved LRC was
      significantly associated with FGF-2-negativity [risk ratio (RR): 7.33; 95%
      confidence interval (CI): 2.88-19.05; p<0.001], lower T-category (RR: 2.42; 95%
      CI: 1.47-4.33; p<0.001), lower N-category (RR: 12.36; 95%-CI: 3.48-78.91;
      p<0.001), and pre-radiotherapy hemoglobin levels >= 12 g/dl (RR: 4.18; 95%-CI:
      1.73-10.53; p=0.002). No factor was significantly associated with improved MFS.
      Lower T-category showed a trend (RR: 1.59; 95%-CI: 0.97-2.82; p=0.069). Better OS
      was significantly associated with FGF-2-negativity (RR: 5.10; 2.22-11.80;
      p<0.001), lower T-category (RR: 2.17; 95%-CI: 1.38-3.68; p < 0.001), lower N
      category (RR: 3.86; 95%-CI: 1.60-10.85; p=0.002), and pre-radiotherapy hemoglobin
      levels >= 12 g/dl (RR: 3.20; 95%-CI: 1.46-7.30; p=0.004). HPV-positivity showed a
      trend (RR: 2.36; 95%-CI: n.a.; p=0.054). CONCLUSIONS: Tumor cell expression of
      FGF-2 proved to be an independent prognostic factor for LRC and OS. This factor
      can help personalize treatment and stratify patients in future trials.

PMID- 23861153
TI  - A survival score for patients with brain metastases from less radiosensitive
      tumors treated with whole-brain radiotherapy alone.
AB  - BACKGROUND AND PURPOSE: This study aimed to develop and validate a scoring system
      to predict the survival of patients receiving whole-brain radiotherapy (WBRT)
      alone for brain metastases from less radiosensitive tumors. PATIENTS AND METHODS:
      The study included data from 176 patients with brain metastasis from renal cell
      carcinoma, malignant melanoma or colorectal cancer. Patients were divided into a
      test group (N=88) and a validation group (N=88). In the multivariate analysis of
      the test group, age, Karnofsky Performance Status and extracranial metastasis
      were significantly associated with survival. These three factors were included in
      the scoring system. The score for each factor was determined by dividing the 6
      month survival rate (in %) by 10. The total score represented the sum of the
      three scores. According to the total scores-which ranged from 5 to 14 points
      three prognostic groups were created. RESULTS: The 6-month survival rates in the
      test group were 11% for 5-8 points (N=47, group A), 38% for 9-11 points (N=29,
      group B) and 83% for 12-14 points (N=12, group C). In the validation group the 6
      month survival rates were 12, 31 and 75%, respectively. Comparisons between the
      prognostic groups A, B and C of the test group with those of the validation group
      did not reveal any significant differences. CONCLUSION: The new scoring system
      based on three independent prognostic factors can help to estimate the survival
      of patients with brain metastases from a less radiosensitive tumor. The score
      appears to be valid and reproducible.

PMID- 23861155
TI  - [In Process Citation].

PMID- 23861154
TI  - Reirradiation plus EGFR inhibition in locally recurrent and unresectable head and
      neck cancer: final results from a single institution.
AB  - PURPOSE: For some patients with recurrent, unresectable, and previously
      irradiated head and neck squamous cell carcinoma (HNSCC), reirradiation (re-RT)
      may be a curative option. Chemotherapy with epidermal growth factor receptor
      (EGFR) inhibition is established as palliative management. This retrospective
      single-institutional study investigates feasibility, toxicity, and outcome of
      reirradiation (re-RT) combined with EGFR blockade for these patients. PATIENTS
      AND METHODS: Between June 2008 and June 2012, 23 patients with inoperable and
      previously irradiated HNSCC were reirradiated. Concomitant EGFR blockade
      (cetuximab) was given initially at 400 mg/m2 two days prior to re-RT and weekly
      (250 mg/m2) thereafter. PET/CT imaging was fused with planning CT in 8 patients.
      RESULTS: One patient died of anaphylactic shock during the first cetuximab
      administration; two discontinued treatment on their own request. In all, 20
      patients completed re-RT (50.4-66.6 Gy) and received cetuximab as prescribed.
      Grade 3 acute side effects were documented for dermatitis (35%), dysphagia (30%),
      acneiform rash (30%), and mucositis (15%). The 1-year overall survival rate was
      34.8% Median overall and progression-free survival times were 9 and 4.3 months,
      respectively. A multivariable analysis using the Cox regression model showed
      significant positive impact of acneiform rash (hazard ratio [HR] 0.1531, 95%
      confidence interval [CI] 0.0383-0.6111), while a period from first radiation to
      re-RT longer than 120 months negatively (HR 0.1633, 95% CI 0.0305-0.8734)
      influenced patient survival. CONCLUSION: re-RT with concurrent cetuximab was
      feasible. Compared to platinum-based chemotherapy with fluorouracil and
      cetuximab, this therapeutic approach did not demonstrate survival benefit.
      Prolonged intervals from first treatment to re-RT seem to be unfavorable.

PMID- 23861156
TI  - [In Process Citation].

PMID- 23861157
TI  - [In Process Citation].

PMID- 23861159
TI  - Efficacy of alogliptin, a dipeptidyl peptidase-4 inhibitor, on glucose
      parameters, the activity of the advanced glycation end product (AGE) - receptor
      for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes.
AB  - BACKGROUND: To examine the effects of alogliptin, a dipeptidyl peptidase-4
      inhibitor, on glucose parameters, the advanced glycation end product (AGE)
      receptor for AGE (RAGE) axis and albuminuria in Japanese type 2 diabetes
      patients. METHODS: Sixty-one patients whose HbAlc  >= 6.1% (mean age 64.7 years;
      67% men; mean HbAlc 7.4%; 57% were pharmacologically treated) underwent blood and
      urine sampling and analysis before and after 12 weeks of treatment with
      alogliptin (25 mg once daily). RESULTS: Alogliptin treatment significantly
      reduced fasting glucose (160.3 mg/dL at baseline versus 138.0 mg/dL at 12 weeks),
      glycoalbumin (21.1% at baseline versus 18.9% at 12 weeks), HbAlc (7.4% at
      baseline versus 6.9% at 12 weeks), circulating soluble form of RAGE
      concentrations (847.3 pg/mL at baseline versus 791.4 pg/mL at 12 weeks) and urine
      albumin to creatinine ratio (31.6 mg/g Cr at baseline versus 26.5 mg/g Cr at 12
      weeks), whereas 1,5-anhydroglucitol concentrations were significantly increased
      (7.5 ug/mL at baseline versus 11.6 ug/mL at 12 weeks; all P < 0.05). Circulating
      AGEs concentrations were reduced only in patients with baseline AGEs >=7 U/mL (n
      = 33, from 8.2 U/mL to 7.2U /mL; p < 0.01) after alogliptin treatment. The
      treatment-induced change of soluble form of sRAGE concentrations was associated
      with changes of 1,5-anhydroglucitol and HbAlc concentrations (rho = -0.32 and
      0.29, respectively). Meanwhile, the treatment-induced change of urine albumin to
      creatinine ratio was associated with a change in the fasting glucose
      concentration (rho = 0.25; all p < 0.05). During the intervention, alogliptin
      treatment was well tolerated without any hypoglycemia or side effects.
      CONCLUSION: Alogliptin treatment improved the AGE-RAGE axis and reduced
      albuminuria in Japanese type 2 diabetes patients.

PMID- 23861158
TI  - Impact of hemochromatosis gene mutations on cardiac status in doxorubicin-treated
      survivors of childhood high-risk leukemia.
AB  - BACKGROUND: Doxorubicin is associated with progressive cardiac dysfunction,
      possibly through the formation of doxorubicin-iron complexes leading to free
      radical injury. The authors determined the frequency of hemochromatosis (HFE)
      gene mutations associated with hereditary hemochromatosis and their relationship
      with doxorubicin-associated cardiotoxicity in survivors of childhood high-risk
      acute lymphoblastic leukemia. METHODS: Peripheral blood was tested for 2 common
      HFE allelic variants: C282Y and H63D. Serum cardiac troponin-T (cTnT) and N
      terminal pro-brain natriuretic peptide (NT-proBNP), which are biomarkers of
      cardiac injury and cardiomyopathy, respectively, were assayed during therapy.
      Left ventricular (LV) structure and function were assessed with echocardiography.
      RESULTS: A total of 184 patients had DNA results for at least 1 variant, and 167
      had DNA results for both: 24% carried H63D and 10% carried C282Y. Heterozygous
      C282Y genotype was associated with multiple elevations in cTnT concentrations (P
      = .039), but not NT-proBNP. At a median of 2.2 years (range, 1.0 years-3.6 years)
      after diagnosis, the mean Z-scores for LV fractional shortening (-0.71 [standard
      error (SE), 0.25]; P = .008), mass (-0.84 [SE, 0.17]; P < .001), and end-systolic
      (-4.36 [SE, 0.26], P < .001) and end-diastolic (-0.68 [SE, 0.25]; P = .01)
      posterior wall thickness were found to be abnormal in children with either allele
      (n = 32). Noncarriers (n = 63) also were found to have below-normal LV mass (
      0.45 [SE, 0.15]; P = .006) and end-systolic posterior wall thickness (-4.06 [SE,
      0.17]; P < .001). Later follow-up demonstrated similar results. CONCLUSIONS:
      Doxorubicin-associated myocardial injury was associated with C282Y HFE carriers.
      Although LV mass and wall thickness were found to be abnormally low overall, they
      were even lower in HFE carriers, who also had reduced LV function. Screening
      newly diagnosed cancer patients for HFE mutations may identify those at risk for
      doxorubicin-induced cardiotoxicity.

PMID- 23861160
TI  - Cervical disc deformation during flexion-extension in asymptomatic controls and
      single-level arthrodesis patients.
AB  - The aim of this study was to characterize cervical disc deformation in
      asymptomatic subjects and single-level arthrodesis patients during in vivo
      functional motion. A validated model-based tracking technique determined
      vertebral motion from biplane radiographs collected during dynamic flexion
      extension. Level-dependent differences in disc compression-distraction and shear
      deformation were identified within the anterior and posterior annulus (PA) and
      the nucleus of 20 asymptomatic subjects and 15 arthrodesis patients using a mixed
      model statistical analysis. In asymptomatic subjects, disc compression and shear
      deformation per degree of flexion-extension progressively decreased from C23 to
      C67. The anterior and PA experienced compression-distraction deformation of up to
      20%, while the nucleus region was compressed between 0% (C67) and 12% (C23). Peak
      shear deformation ranged from 16% (at C67) to 33% (at C45). In the C5-C6
      arthrodesis group, C45 discs were significantly less compressed than in the
      control group in all disc regions (all p <= 0.026). In the C6-C7 arthrodesis
      group, C56 discs were significantly less compressed than the control group in the
      nucleus (p = 0.023) and PA (p = 0.014), but not the anterior annulus (AA; p =
      0.137). These results indicate in vivo disc deformation is level-dependent, and
      single-level anterior arthrodesis alters the compression-distraction deformation
      in the disc immediately superior to the arthrodesis.

PMID- 23861161
TI  - Validation of quality indicators for the organization of palliative care: a
      modified RAND Delphi study in seven European countries (the Europall project).
AB  - BACKGROUND: Validated quality indicators can help health-care professionals to
      evaluate their medical practices in a comparative manner to deliver optimal
      clinical care. No international set of quality indicators to measure the
      organizational aspects of palliative care settings exists. AIM: To develop and
      validate a set of structure and process indicators for palliative care settings
      in Europe. DESIGN: A two-round modified RAND Delphi process was conducted to rate
      clarity and usefulness of a previously developed set of 110 quality indicators.
      SETTING/PARTICIPANTS: In total, 20 multi-professional palliative care teams of
      centers of excellence from seven European countries. RESULTS: In total, 56
      quality indicators were rated as useful. These valid quality indicators concerned
      the following domains: the definition of a palliative care service (2 quality
      indicators), accessibility to palliative care (16 quality indicators), specific
      infrastructure to deliver palliative care (8 quality indicators), symptom
      assessment tools (1 quality indicator), specific personnel in palliative care
      services (9 quality indicators), documentation methodology of clinical data (14
      quality indicators), evaluation of quality and safety procedures (1 quality
      indicator), reporting of clinical activities (1 quality indicator), and education
      in palliative care (4 quality indicator). CONCLUSION: The modified RAND Delphi
      process resulted in 56 international face-validated quality indicators to measure
      and compare organizational aspects of palliative care. These quality indicators,
      aimed to assess and improve the organization of palliative care, will be pilot
      tested in palliative care settings all over Europe and be used in the EU FP7
      funded IMPACT project.

PMID- 23861162
TI  - [Resistance to medicinal tumor therapy. Current status].
AB  - In the past multiple mechanisms could be identified that are involved in
      anticancer drug resistance; however, diagnostic assays for prediction of therapy
      response to classical cytostatic drugs did not enter routine clinical
      diagnostics. Only when new targeted drugs, e.g. tyrosine kinase inhibitors or
      therapeutic antibodies, were introduced in oncology were diagnostics for
      prediction of therapy response routinely preformed. First and foremost this was
      the result of the development of highly standardized techniques, i.e. exact
      mutation analysis in functional relevant codons of genes encoding signal proteins
      of cancer-related signal transduction pathways targeted by the new drugs. Due to
      increasing costs of health systems, in the future predictive diagnostics will
      probably become more and more important. Therefore, it will be necessary to
      develop improved diagnostic assays for prediction of individual therapy response.

PMID- 23861163
TI  - First-year radiographic progression as a predictor of further progression in
      early arthritis: results of a large national French cohort.
AB  - OBJECTIVE: A major goal in the treatment of recent arthritis is the prevention of
      joint destruction. The value of radiographic progression in the first year for
      predicting further radiographic progression has not been evaluated comparatively
      with conventional predictive factors. METHODS: Patients with arthritis of <6
      months' duration were included in the prospective French ESPOIR cohort.
      Radiographs were obtained and modified Sharp scores were determined by a blinded
      reader. The rate of progression was determined over the first year, then over the
      second and third years. Rapid progression was defined as a >5-point annual
      increase in the total Sharp score. RESULTS: In total, 500 patients had complete
      data available after 3 years and were included. The total Sharp score indicated
      rapid progression in 123 patients (25%) in year 1 and 92 patients (18%) in years
      2/3. By logistic regression, the variables independently associated with rapid
      progression in years 2/3 were year 1 rapid progression of the erosion and total
      Sharp scores, baseline erosion Sharp score, the serologic American College of
      Rheumatology/European League Against Rheumatism criterion, and interleukin-6
      level. When these variables were combined, year 1 rapid progression made the
      largest contribution to predicting years 2/3 rapid progression. CONCLUSION: First
      year radiologic progression is the best independent predictor of further rapid
      progression in early arthritis.

PMID- 23861164
TI  - SPE-HPLC-MS/MS method for the trace analysis of tobacco-specific N-nitrosamines
      and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in rabbit plasma using
      tetraazacalix[2]arene[2]triazine-modified silica as a sorbent.
AB  - Tobacco-specific N-nitrosamines (TSNAs), including N'-nitrosonornicotine, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone, N'-nitrosoanatabine, and N'
      nitrosoanabasine, have been implicated as a source of carcinogenicity in tobacco
      and cigarette smoke. We present a rapid and effective method comprising SPE based
      on tetraazacalix[2]arene[2]triazine-modified silica as sorbent and analysis with
      HPLC-MS/MS for the determination of TSNAs and 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanol (NNAL), a metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone,
      in rabbit plasma. The linear dynamic ranges were 10-2000 pg/mL for NNAL and 4
      2000 pg/mL for the four TSNAs with good correlation coefficients (>0.9965). The
      LODs were in the range of 0.9-3.7 pg/mL, and the LOQs were between 2.9 and 12.3
      pg/mL. The accuracies of the method were also evaluated and found to be in the
      range of 90.1-113.3%. This method is promising to be applied to the
      preconcentration and determination of TSNAs and NNAL in smoke and human body
      fluids. 

PMID- 23861166
TI  - Evaluation of residual viremia and quantitation of soluble CD14 in a large cohort
      of HIV-infected adults on a long-term non-nucleoside reverse transcriptase
      inhibitor-based regimen.
AB  - Beyond virological suppression and immunologic recovery, the objective of long
      term antiretroviral therapy is to suppress maximally viremia and to control for
      persistent immune activation. Non-nucleoside reverse transcriptase inhibitor
      (NNRTI)-containing regimens are associated with lower residual viremia. The
      objective of the study was to evaluate the impact of long term NNRTI-containing
      treatment on residual viremia and on monocyte activation in a cohort of patients
      infected with HIV-1. To identify factors associated with residual viremia, adult
      patients infected with HIV on nevirapine or efavirenz-based therapy with viral
      load <50 copies/ml for >6 months were included. Residual plasma viremia was
      quantified using an adapted Cobas/Taqman HIV-1 assay. Viral loads with no
      detected signal were considered as <1 copy/ml. Monocyte activation was evaluated
      by quantitation of plasma sCD14 by ELISA assay at the time of residual viremia
      measurement. Logistic regression was used to determine factors associated with
      residual viremia <1 copy/ml. In this cohort of 421 patients on long-term NNRTI
      regimen, three quarters had a residual viremia <1 copy/ml. In multivariate
      analysis, duration of plasma viral load below 50 copies/ml was the only factor
      associated with residual viremia <1 copy/ml. Soluble CD14 was in the normal range
      although treatment with nevirapine was associated with a significant lower level
      of sCD14 compared to efavirenz. Residual viremia <1 copy/ml was frequent in this
      cohort of patients with long term virological control and confirmed the results
      of previous studies. Apart from its antiviral effect, nevirapine as well as
      efavirenz could decrease monocyte activation.

PMID- 23861165
TI  - Enduring influence of early temperament on neural mechanisms mediating attention
      emotion conflict in adults.
AB  - BACKGROUND: Behavioral inhibition, a temperament identified in early childhood,
      is often associated with dysregulated attention and affective processing,
      particularly in response to threat. Longitudinal studies find that the
      manifestation of perturbed attention and affective processing often dissipates
      with age. Yet, childhood behavioral inhibition continues to predict perturbed
      brain function into adulthood. This suggests that adults with childhood
      behavioral inhibition may engage compensatory processes to effectively regulate
      emotion-related attention. However, it is unknown whether perturbations in brain
      function reflect compensation for attention bias to emotional stimuli generally,
      or to threatening contexts more specifically. The present study tests these
      possibilities. METHODS: Adults with and without a history of stable childhood
      behavioral inhibition completed an attention-control task in the context of
      threatening and nonthreatening stimuli while undergoing functional magnetic
      resonance imaging. Participants were asked to identify the gender of fearful
      (threatening) and happy (nonthreatening) faces, while ignoring both the face
      emotion and overlaid congruent (low attention control, LAC) or incongruent (high
      attention control, HAC) gender words. RESULTS: When fearful faces were present,
      adults with stable childhood behavioral inhibition exhibited more activity in
      striatum, cingulate, and dorsolateral prefrontal cortex for HAC trials compared
      with LAC trials, relative to those without behavioral inhibition. When happy
      faces were present, the opposite activation pattern emerged. No group differences
      in behavior were observed. CONCLUSIONS: Among adults, stable childhood behavioral
      inhibition predicts neural, but not behavioral, responding when attention control
      is engaged in discrete emotional contexts. This suggests a mechanism by which
      adults may compensate for the behavioral manifestation of threat-based attention
      biases.

PMID- 23861167
TI  - Identifying youth at risk for difficulties following a traumatic event: pre-event
      factors are associated with acute symptomatology.
AB  - This study examined factors related to children's acute symptoms following a
      potentially traumatic event (PTE) to more clearly identify domains that should be
      included in screenings of youth exposed to a PTE. In particular, the authors
      examined whether trauma category (i.e., sexual abuse/disclosure of abuse,
      intentionally perpetrated traumas other than sexual abuse, and unintentional
      traumas) was related to symptoms after controlling for other relevant factors.
      Participants were 112 youth presenting for clinical evaluation within a month of
      a PTE and their nonoffending caregivers. Using data from baseline assessments
      collected as part of a randomized controlled trial of a secondary prevention
      program, the following factors were tested in 3 hierarchical regression models:
      index PTE category, history of traumatic exposure, preindex event functioning,
      and parenting behaviors. Prior trauma exposure, preindex event functioning, and
      hostile parenting were uniquely related to children's symptoms in the acute
      posttraumatic period after controlling for time since the event and child age,
      but trauma category was not. Implications for identifying and referring children
      at high risk for poor outcomes in the early aftermath of a PTE are discussed. An
      exclusive focus on the event is insufficient and more comprehensive understanding
      of the child and family is required. 

PMID- 23861168
TI  - In vitro and mouse in vivo characterization of the potent free fatty acid 1
      receptor agonist TUG-469.
AB  - Activation of the G protein-coupled free fatty acid receptor 1 (FFA1; formerly
      known as GPR40) leads to an enhancement of glucose-stimulated insulin secretion
      from pancreatic beta-cells. TUG-469 has previously been reported as a potent FFA1
      agonist. This study was performed to confirm the higher in vitro potency of TUG
      469 compared to the reference FFA1 agonist GW9508 and to prove in vivo activity
      in a pre-diabetic mouse model. The in vitro pharmacology of TUG-469 was studied
      using Ca(2+)-, cAMP-, and impedance-based assays at recombinant FFA1 and free
      fatty acid receptor 4, formerly known as GPR120 (FFA4) expressing 1321N1 cells
      and the rat insulinoma cell line INS-1. Furthermore, we investigated the systemic
      effect of TUG-469 on glucose tolerance in pre-diabetic New Zealand obese (NZO)
      mice performing a glucose tolerance test after intraperitoneal administration of
      5 mg/kg TUG-469. In comparison to GW9508, TUG-469 showed a 1.7- to 3.0-times
      higher potency in vitro at 1321N1 cells recombinantly expressing FFA1. Both
      compounds increased insulin secretion from rat insulinoma INS-1 cells. TUG-469 is
      > 200-fold selective for FFA1 over FFA4. Finally, a single dose of 5 mg/kg TUG
      469 significantly improved glucose tolerance in pre-diabetic NZO mice. TUG-469
      turned out as a promising candidate for further drug development of FFA1 agonists
      for treatment of type 2 diabetes mellitus.

PMID- 23861169
TI  - Are physician recommendations for BRCA1/2 testing in patients with breast cancer
      appropriate? A population-based study.
AB  - BACKGROUND: To the best of the authors' knowledge, few population-based studies
      to date have examined the use of BRCA1/2 testing or patterns of physician
      recommendations for genetic testing among women diagnosed with breast cancer. The
      objective of the current study was to evaluate the rates and predictors of
      physician recommendation for BRCA1/2 testing among patients with breast cancer.
      METHODS: Women aged 18 years to 64 years who were diagnosed with invasive breast
      cancer in 2007 were identified from the Pennsylvania Cancer Registry and mailed a
      survey regarding their family history of cancer, physician treatment
      recommendations, and BRCA1/2 testing. Of the 4009 women who were sent surveys,
      2258 responded (56%). Based on age at diagnosis and family history, women were
      categorized as being at high, moderate, or low risk of BRCA1/2 mutations.
      RESULTS: Nearly 25% of the participants were classified as being at high risk of
      carrying a BRCA1/2 mutation based on their age at the time of breast cancer
      diagnosis and family history of breast and/or ovarian cancer. Physician
      recommendations for BRCA1/2 testing were found to be strongly associated with
      risk of carrying a mutation, with 53% of high-risk women reporting a testing
      recommendation compared with 9% of low-risk women. In addition, physician
      recommendations were strongly correlated with the use of testing in all risk
      groups. Among high-risk women, the lack of a recommendation for BRCA1/2 testing
      was more common among older, low-income, and employed women. CONCLUSIONS:
      Although BRCA1/2 testing recommendations appear to be appropriately correlated
      with mutation risk, a significant percentage of patients with breast cancer who
      meet criteria for BRCA1/2 testing may not receive a recommendation for such
      testing from their health care providers.

PMID- 23861171
TI  - Impact of disease-modifying therapies on the survival of patients with multiple
      sclerosis in Taiwan, 1997-2008.
AB  - BACKGROUND: Little is known about the impact of disease-modifying therapies
      (DMTs) on the survival of patients with multiple sclerosis (MS) throughout the
      world. OBJECTIVE: We conducted this study to investigate the association between
      DMTs and the survival of patients with MS in Taiwan. METHODS: A total of 1,240
      individuals who had a primary diagnosis of MS and a seriously disabling disease
      certificate in Taiwan between 1 January 1997 and 1 December 2008 were followed up
      until 31 December 2009 to check what medical services were provided to them and
      whether they had a date of death recorded in the national mortality database.
      Disease-modifying therapies, including interferon beta 1-a, interferon beta 1-b
      and glatiramer acetate, were included in the analysis. Follow-up information was
      available on all individuals; the mean follow-up time was 54.3 months (standard
      deviation [SD] 38.8 months). A Cox regression model was utilized to reveal the
      effect of DMTs on MS mortality by controlling for sex, age, residence, insurance
      amount and geographic region. RESULTS: Eighty-eight of the 1,240 individuals (7.1
      %) died. The risk of mortality in the first year showed a 7-fold age- and sex
      standardized mortality rate increase over that of the general population in
      Taiwan. In the fully adjusted model, the final independent risk factors were
      older age, rural residence, lower economic status and lower adherence to DMTs.
      CONCLUSION: The results of this study support the notion that DMTs can improve
      the survival of patients with MS, and show that individuals with the risk factors
      of older age, rural residence and lower economic status had a higher MS-related
      mortality risk in Taiwan.

PMID- 23861170
TI  - Adipose tissue insulin resistance in adolescents with and without type 2
      diabetes.
AB  - BACKGROUND: The incidence of type 2 diabetes mellitus (T2D) is increasing in
      youth, yet little is known about the underlying pathophysiology. Decreased
      insulin suppression of lipolysis and elevated non-esterified free fatty acid
      (NEFA) concentrations are known to be associated with insulin resistance and T2D
      in adults, but less is known about the relationship in adolescents. OBJECTIVES:
      This study aimed to assess adipose tissue insulin resistance (IR; insulin
      suppression of lipolysis) and its metabolic correlates in lean, obese and T2D
      adolescents. METHODS: Forty-seven lean, obese and T2D youth underwent
      hyperinsulinaemic (80 mU*m(-2) *min(-1)) euglycaemic clamps. NEFAs were measured
      at baseline and during steady state. Insulin-mediated suppression of lipolysis
      (%NEFA suppression from baseline) was calculated, and metabolic risk factors were
      assessed by %NEFA suppression tertile. RESULTS: There was expected variability in
      %NEFA suppression within obese and T2D youth, but a subset had significantly
      reduced suppression of lipolysis. NEFA suppression tertile was significantly
      inversely associated with fasting triglycerides (P = 0.0001), log alanine
      aminotransferase (ALT; P = 0.02) and low-density lipoprotein cholesterol (P =
      0.0002). CONCLUSIONS: Marked adipose tissue IR occurs in some obese and T2D
      adolescents, which may result in release of triglycerides into the circulation
      and liver deposition of fatty acids, as evidenced by higher ALT in poor NEFA
      suppressors.

PMID- 23861172
TI  - [Individualization of guidelines. Approach for rectal cancer in UICC stages II
      and III].
AB  - BACKGROUND: The German guidelines for the therapy of rectal carcinoma in Union
      Internationale Contre le Cancer (UICC) stages II and III raise questions of
      overtherapy. This is why we have individualized the therapy in suitable isolated
      cases (localization in the upper third of the rectum and wider safety margins in
      cases of small T3). MATERIAL AND METHODS: All 131 patients with rectal cancer
      stages II and III, who were operated on within a time period of 4 years were
      retrospectively included in the study. In 30 favorable cases no radiotherapy was
      given and in 15 of these no chemotherapy. After an average of 57 months follow-up
      the course of the disease could be clarified in 95 % of the patients. RESULTS:
      The 5-year survival rate in the whole group was 81.5 % with a local recurrence
      rate of 8 %. Of the patients with no additional therapy (or only adjuvant
      chemotherapy), 30 had a 5-year survival rate of 100 % (86.7 %) and a local
      recurrence rate of 6.7 % (6.7 %). CONCLUSIONS: In this study it could be shown
      that an individualization of guidelines in special cases does not lead to a
      higher mortality rate or to a higher rate of local recurrence. The study
      highlights that chemotherapy and radiotherapy with all the negative consequences
      could be avoided for several patients.

PMID- 23861173
TI  - Continuous rise of insulin resistance before and after the onset of puberty in
      children at increased risk for type 1 diabetes - a cross-sectional analysis.
AB  - BACKGROUND: Insulin resistance has been postulated to be linked to the frequent
      onset of type 1 diabetes (T1D) during puberty. Very few studies have investigated
      the time course of insulin resistance in childhood. To address the question of
      how insulin resistance develops with age and how this is related to puberty
      onset, we examined insulin resistance and pubertal development over time in
      children at increased risk for T1D. METHODS: Homeostasis model assessment of
      insulin resistance (HOMA-IR) was measured in 1848 fasting samples of 1177
      children (aged 5-15 years) in a cross-sectional analysis. All children had a
      first degree relative with T1D, 120 developed islet autoantibodies. Pubertal
      development was determined by Tanner staging. RESULTS: Insulin resistance rose
      continuously from age 5 to 13 years in girls and from age 5 to 14 years in boys
      with an average increase of 0.09 (95 % confidence interval [CI]: 0.08-0.10) per
      year for girls and 0.07 (95 % CI: 0.06-0.08) for boys. The rise preceded the
      onset of puberty (Tanner stage 2), which was reported between 10 and 12 years of
      age in 80.4 % of the children (mean age: 11.2 +/- 0.06 years). No difference was
      seen between children with or without islet autoantibodies. CONCLUSIONS: There
      was a constant age-dependent rise of insulin resistance during childhood without
      observed associations to the onset of puberty or the presence of islet
      autoimmunity in children at increased risk for T1D. Our data show that insulin
      resistance emerges well before the initiation of physical changes of puberty.

PMID- 23861174
TI  - Histologic and functional outcomes of nerve defects treated with acellular
      allograft versus cabled autograft in a rat model.
AB  - PURPOSE: Acellular nerve allograft is a new option for bridging nerve defects
      that allows appropriate diameter matching. The aim of the study was to compare
      the histologic and functional recovery of nerve defects treated with acellular
      nerve allograft versus cabled sural nerve autograft. METHOD: Fifty-four Sprague
      Dawley rats were divided into one of three experimental groups. A unilateral 10
      mm sciatic nerve defect was created and repaired with an acellular nerve
      allograft (Group A), three cabled sural nerve autografts in antidromic
      orientation (Group B), and the newly created segmental defect in antidromic
      orientation (reversed autograft) (Group C). Two rats in each group we evaluated
      histologically at 6 weeks while the rest of the groups were tested histologically
      and functionally at 12 weeks. RESULTS: There were no differences in
      histomorphometry between the groups at 6 weeks, but at 12 weeks at mid-graft
      there were differences. Group C had the highest fiber count which was
      statistically greater when compared to Group A (P = 0.023) and when compared to
      Group B (P = 0.001). The average normalized maximum isometric tetanic force (ITF)
      was 52 +/- 2.9% for Group A, 34.1 +/- 4.2% for Group B, and 51.3 +/- 3.3% for
      Group C at 12 weeks. There was no statistical difference between Groups A and C,
      but Group A was statistically greater when compared to B, and when Group C was
      compared to B. CONCLUSION: In conclusion, acellular nerve allograft demonstrated
      equal functional recovery when compared to reversed autograft (control), and
      superior recovery compared to the cabled nerve autograft.

PMID- 23861175
TI  - Raft localization of type I Fcepsilon receptor and degranulation of RBL-2H3 cells
      exposed to decavanadate, a structural model for V2O5.
AB  - Vanadium oxides (VOs) have been identified as low molecular weight sensitizing
      agents associated with occupational asthma and compromised pulmonary
      immunocompetence. Symptoms of adult onset asthma result, in part, from increased
      signal transduction by Type I Fcepsilon receptors (FcepsilonRI) leading to
      release of vasoactive compounds including histamine from mast cells. Exposure to
      (VOs) typically occurs in the form of particles which are insoluble. Upon contact
      with water or biological fluids, (VOs) form a series of soluble oxoanions, one of
      which is decavanadate, V10O28(6-) abbreviated V10, which is structurally related
      to a common vanadium oxide, that is vanadium pentoxide, V2O5. Here we investigate
      whether V10 may be initiating plasma membrane events associated with activation
      of FcepsilonRI signal transduction. We show that exposure of RBL-2H3 cells to V10
      causes a concentration-dependent increase in degranulation of RBL-2H3 and, in
      addition, an increase in plasma membrane lipid packing as measured by the
      fluorescent probe, di-4-ANEPPDHQ. V10 also increases FcepsilonRI accumulation in
      low-density membrane fragments, i.e., lipid rafts, which may facilitate
      FcepsilonRI signaling. To determine whether V10 effects on plasma membrane lipid
      packing were similarly observed in Langmuir monolayers formed from
      dipalmitoylphosphatidylcholine (DPPC), the extent of lipid packing in the
      presence and absence of V10 and vanadate was compared. V10 increased the surface
      area of DPPC Langmuir monolayers by 6% and vanadate decreased the surface area by
      4%. These results are consistent with V10 interacting with this class of membrane
      lipids and altering DPPC packing. 

PMID- 23861177
TI  - Water oxidation catalysis via immobilization of the dimanganese complex [Mn2(MU
      O)2Cl(MU-O2CCH3)(bpy)2(H2O)](NO3)2 onto silica.
AB  - Adsorption of a dinuclear MU-oxo bridged Mn complex onto mesoporous silica was
      observed when SBA15 was treated with an acetonitrile solution of [Mn2(MU-O)2Cl(MU
      O2CCH3)(H2O)(bpy)2](NO3)2 (1). This complex was immobilized via the displacement
      of NO3(-) into solution, and characterization by spectroscopic (DRIFTS and DRUV
      vis) and magnetic data indicates that the intact dication is electrostatically
      bound to the silica surface. Loadings of up to 4.1% by weight of [Mn2(MU-O)2Cl(MU
      O2CCH3)(H2O)(bpy)2](2+) were achieved. TEM images of the grafted material
      revealed retention of the mesoporous structure of SBA15, and no clusters of
      manganese greater than ca. 10 nm were observed. The SBA15-supported dimanganese
      complex functions as a catalyst for the oxidation of H2O with (NH4)2Ce(NO3)6 as
      stoichiometric oxidant. In contrast, homogenous aqueous solutions of 1 do not
      evolve oxygen upon treatment with (NH4)2Ce(NO3)6. Labeling studies with H2(18)O
      confirm that the oxygen formed in this catalysis is derived from water.
      Monitoring the O2 evolution allowed determination of an initial rate for the
      catalysis (TOFi = 1.1 * 10(-3) s(-1)). These studies also reveal a first order
      dependence on manganese surface concentration, and a zero order rate dependence
      for (NH4)Ce(NO3)6. Spectroscopic investigations were employed to investigate the
      difference in activities between dissolved and supported dimanganese complexes. 

PMID- 23861176
TI  - Association of planus foot posture and pronated foot function with foot pain: the
      Framingham foot study.
AB  - OBJECTIVE: To examine the associations of foot posture and foot function to foot
      pain. METHODS: Data were collected on 3,378 members of the Framingham Study
      cohort who completed foot examinations in 2002-2008. Foot pain (generalized and
      at 6 locations) was based on the response to the following question: "On most
      days, do you have pain, aching or stiffness in either foot?" Foot posture was
      categorized as normal, planus, or cavus using static pressure measurements of the
      arch index. Foot function was categorized as normal, pronated, or supinated using
      the center of pressure excursion index from dynamic pressure measurements. Sex
      specific multivariate logistic regression models were used to examine the effect
      of foot posture and function on generalized and location-specific foot pain,
      adjusting for age and weight. RESULTS: Planus foot posture was significantly
      associated with an increased likelihood of arch pain in men (odds ratio [OR]
      1.38, 95% confidence interval [95% CI] 1.01-1.90), while cavus foot posture was
      protective against ball of foot pain (OR 0.74, 95% CI 0.55-1.00) and arch pain
      (OR 0.64, 95% CI 0.48-0.85) in women. Pronated foot function was significantly
      associated with an increased likelihood of generalized foot pain (OR 1.28, 95% CI
      1.04-1.56) and heel pain (OR 1.54, 95% CI 1.04-2.27) in men, while supinated foot
      function was protective against hindfoot pain in women (OR 0.74, 95% CI 0.55
      1.00). CONCLUSION: Planus foot posture and pronated foot function are associated
      with foot symptoms. Interventions that modify abnormal foot posture and function
      may therefore have a role in the prevention and treatment of foot pain.

PMID- 23861178
TI  - Dissolution of prednisone tablets in the presence of an arch-shaped fiber optic
      probe in a USP dissolution testing apparatus 2.
AB  - During dissolution testing of solid dosage forms in the United States
      Pharmacopoeia (USP) Apparatus 2, samples are manually withdrawn from the medium
      in the vessel prior to the analysis. Probes permanently inserted in the medium
      can automate the sampling process but can also alter the system's hydrodynamics,
      possibly resulting in different dissolution-testing results. In this work,
      dissolution tests were conducted in a USP Apparatus 2 with and without an arch
      shaped fiber optic probe using prednisone tablets fixed at nine different
      locations on the vessel bottom. The resulting dissolution profiles were compared
      using statistical tools. Dissolution rates obtained with the probe were typically
      higher than those obtained without the probe. The magnitude of the difference
      between dissolution profiles depended on the tablet location: Larger differences
      were observed with tablets located immediately downstream of the probe. The
      differences in dissolution profiles were generally small enough to satisfy the US
      Food and Drug Administration criteria (f1 and f2 values), although a paired t
      test [P(t-test)] indicated that most of the profiles were statistically different
      [P(t-test) <0.05]. The hydrodynamic effects generated by the arch-shaped fiber
      optic probe resulted in detectable differences in the dissolution profiles,
      which, although limited, were clearly measurable and could introduce variations
      in test results.

PMID- 23861179
TI  - Application of anion-exchange imidazolium silica for the multiphase dispersive
      extraction of phenolic acids.
AB  - This paper reports the application of a multiphase dispersive extraction method
      to the extraction, separation, and determination of the phenolic acids from
      Salicornia herbacea L. using silica-confined ionic liquids as sorbents. A
      suitable sorbent for phenolic acid extraction and separation was first identified
      based on the adsorption behavior of the phenolic acids on different silica
      confined ionic liquids. The sample was then mixed with the optimized sorbent and
      solvent to achieve multiphase dispersive extraction. The sample/sorbent ratio was
      optimized using theoretical calculations from the adsorption isotherm and
      experiments. After transferring the supernatant to an empty cartridge, an SPE
      process was used to separate the three phenolic acids from the other
      interference. Through systematic optimization, the optimal conditions produced
      high recovery rates of protocatechuic acid (91.20%), caffeic acid (94.03%), and
      ferulic acid (91.33%). Overall, the proposed method is expected to have wide
      applicability. 

PMID- 23861181
TI  - Gender differences in subjective sleep after trauma and the development of
      posttraumatic stress disorder symptoms: a pilot study.
AB  - Women are at higher risk than men for developing posttraumatic stress disorder
      (PTSD) following certain types of trauma such as accidents and assaults. Sleep
      disturbances have been implicated in the development of PTSD. Although gender
      differences in objective sleep soon after trauma have been found in a prior
      polysomnographic study, gender differences in subjective sleep soon after trauma
      and their associations to the development of PTSD have not been examined. This
      pilot study prospectively examined whether gender moderated the relationship
      between subjective sleep soon after trauma and PTSD symptom development. Injury
      patients (17 women, 28 men) completed a sleep questionnaire and a 1-week sleep
      diary 2 weeks after their injuries, and the Clinician Administered PTSD Scale at
      7-weeks postinjury. Results showed that women reported greater frequency of
      nightmares and disruptive nocturnal behaviors (e.g., hot flashes,
      memories/nightmares about trauma) following the trauma and more severe PTSD
      symptoms at 7 weeks. Further, gender moderated the relationship between sleep
      onset latency and PTSD symptom severity, such that longer sleep-onset latency
      predicted more severe PTSD symptoms in men, but less severe PTSD symptoms in
      women. These findings suggest that gender-specific mechanisms may underlie the
      relationship between sleep impairment and the development of PTSD. 

PMID- 23861180
TI  - Patient-reported outcomes of quality of life, functioning, and depressive symptom
      severity in major depressive disorder comorbid with panic disorder before and
      after SSRI treatment in the star*d trial.
AB  - BACKGROUND: Panic disorder (PD) is highly comorbid with major depressive disorder
      (MDD) with potential impact on patient-reported outcomes of quality of life
      (QOL), functioning, and depressive symptom severity. METHODS: Using data from the
      sequenced treatment alternatives to relieve depression (STAR*D) trial, we
      compared entry and post-SSRI-treatment QOL, functioning, and depressive symptom
      severity scores in MDD patients with comorbid PD (MDD+PD) to MDD patients without
      PD (MDDnoPD). We also compared pre- and posttreatment proportions of patients
      with severe impairments in quality of life and functioning. RESULTS: MDD+PD
      patients experienced significantly lower QOL and functioning and more severe
      depressive symptoms than MDDnoPD patients at entry. Following treatment with
      citalopram, both groups showed significant improvements, however, nearly 30-60%
      of patients still suffered from severe quality of life and functioning
      impairments. MDD+PD patients exited with lower QOL and functioning than MDDnoPD
      patients, a difference that became statistically insignificant after adjusting
      for baseline measures of depressive symptom severity, functioning, and QOL,
      comorbid anxiety disorders (PTSD, GAD, social, and specific phobias), age, and
      college education. CONCLUSIONS: Functional outcomes using QOL and functioning
      measures should be utilized in treating and researching MDD so that shortfalls in
      traditional treatment can be identified and additional interventions can be
      designed to address severe baseline QOL and functioning deficits in MDD comorbid
      with PD.

PMID- 23861182
TI  - Structural characterization of electrochemically and in vitro biologically
      generated oxidation products of atorvastatin using UHPLC/MS/MS.
AB  - Ultrahigh-performance liquid chromatography coupled with high-mass-accuracy
      tandem mass spectrometry (UHPLC-MS-MS) has been used for elucidation of the
      structures of oxidation products of atorvastatin (AT), one of the most popular
      commercially available drugs. The purpose of the study was identification of AT
      metabolites in rat hepatocytes and comparison with electrochemically generated
      oxidation products. AT was incubated with rat hepatocytes for 24 h.
      Electrochemical oxidation of AT was performed by use of a three-electrode off
      line system with a glassy carbon working electrode. Three supporting electrolytes
      (0.1 mol L(-1) H2SO4, 0.1 mol L(-1) HCl, and 0.1 mol L(-1) NaCl) were tested, and
      dependence on pH was also investigated. AT undergoes oxidation by a single
      irreversible process at approximately +1.0 V vs. Ag/AgCl electrode. The results
      obtained revealed a simple and relatively fast way of determining the type of
      oxidation and its position, on the basis of characteristic neutral losses (NLs)
      and fragment ions. Unfortunately, different products were obtained by
      electrochemical oxidation and biotransformation of AT. High-mass-accuracy
      measurement combined with different UHPLC-MS-MS scans, for example reconstructed
      ion-current chromatograms, constant neutral loss chromatograms, or exact mass
      filtering, enable rapid identification of drug-related compounds. beta-Oxidation,
      aromatic hydroxylation of the phenylaminocarbonyl group, sulfation, AT lactone
      and glycol formation were observed in rat biotransformation samples. In contrast,
      a variety of oxidation reactions on the conjugated skeleton of isopropyl
      substituent of AT were identified as products of electrolysis. 

PMID- 23861183
TI  - Determination of heavy polycyclic aromatic hydrocarbons of concern in edible oils
      via excitation-emission fluorescence spectroscopy on nylon membranes coupled to
      unfolded partial least-squares/residual bilinearization.
AB  - Seven heavy polycyclic aromatic hydrocarbons (PAHs) of concern on the US
      Environmental Protection Agency priority pollutant list (benzo[a]anthracene,
      benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene,
      dibenz[a,h]anthracene, benzo[g,h,i]perylene, and indeno[1,2,3-c,d]-pyrene) were
      simultaneously analyzed in extra virgin olive oil. The analysis is based on the
      measurement of excitation-emission matrices on nylon membrane and processing of
      data using unfolded partial least-squares regression with residual
      bilinearization (U-PLS/RBL). The conditions needed to retain the PAHs present in
      the oil matrix on the nylon membrane were evaluated. The limit of detection for
      the proposed method ranged from 0.29 to 1.0 MUg kg(-1), with recoveries between
      64 and 78 %. The predicted U-PLS/RBL concentrations compared favorably with those
      measured using high-performance liquid chromatography with fluorescence
      detection. The proposed method was applied to ten samples of edible oil, two of
      which presented PAHs ranging from 0.35 to 0.63 MUg kg(-1). The principal
      advantages of the proposed analytical method are that it provides a significant
      reduction in time and solvent consumption with a similar limit of detection as
      compared with chromatography. 

PMID- 23861184
TI  - Solid-phase extraction method for the isolation of plant thionins from European
      mistletoe, wheat and barley using zirconium silicate embedded in poly(styrene-co
      divinylbenzene) hollow-monoliths.
AB  - Thionins are cysteine-rich, biologically active small (~5 kDa) and basic proteins
      occurring ubiquitously in the plant kingdom. This study describes an efficient
      solid-phase extraction (SPE) method for the selective isolation of these
      pharmacologically active proteins. Hollow-monolithic extraction tips based on
      poly(styrene-co-divinylbenzene) with embedded zirconium silicate nano-powder were
      designed, which showed an excellent selectivity for sulphur-rich proteins owing
      to strong co-ordination between zirconium and the sulphur atoms from the thiol
      group of cysteine. The sorbent provides a combination of strong hydrophobic and
      electrostatic interactions which may help in targeted separation of certain
      classes of proteins in a complex mixture based upon the binding strength of
      different proteins. European mistletoe, wheat and barley samples were used for
      selective isolation of viscotoxins, purothionins and hordothionins, respectively.
      The enriched fractions were subjected to analysis by matrix-assisted laser
      desorption/ionisation-time-of-flight mass spectrometer to prove the selectivity
      of the SPE method towards thionins. For peptide mass-fingerprint analysis,
      tryptic digests of SPE eluates were examined. Reversed-phase high-performance
      liquid chromatography hyphenated to diode-array detection was employed for the
      purification of individual isoforms. The developed method was found to be highly
      specific for the isolation and purification of thionins. 

PMID- 23861185
TI  - Fiberoptic microneedle device facilitates volumetric infusate dispersion during
      convection-enhanced delivery in the brain.
AB  - BACKGROUND AND OBJECTIVES: A fiberoptic microneedle device (FMD) was designed and
      fabricated for the purpose of enhancing the volumetric dispersal of
      macromolecules delivered to the brain through convection-enhanced delivery (CED)
      by concurrent delivery of sub-lethal photothermal hyperthermia. This study's
      objective was to demonstrate enhanced dispersal of fluid tracer molecules through
      co-delivery of 1,064  nm laser energy in an in vivo rodent model. MATERIALS AND
      METHODS: FMDs capable of co-delivering fluids and laser energy through a single
      light-guiding capillary tube were fabricated. FMDs were stereotactically inserted
      symmetrically into both cerebral hemispheres of 16 anesthetized rats to a depth
      of 1.5  mm. Laser irradiation (1,064 nm) at 0 (control), 100, and 200 mW was
      administered concurrently with CED infusions of liposomal rhodamine (LR) or
      gadolinium-Evans blue-serum albumin conjugated complex (Gd-EBA) at a flow rate of
      0.1 ul/min for 1 hour. Line pressures were monitored during the infusions.
      Rodents were sacrificed immediately following infusion and their brains were
      harvested, frozen, and serially cryosectioned for histopathologic and volumetric
      analyses. RESULTS: Analysis by ANOVA methods demonstrated that co-delivery
      enhanced volumetric dispersal significantly, with measured volumes of 15.8  +/- 
      0.6 mm(3) for 100 mW compared to 10.0  +/-  0.4 mm(3) for its fluid only control
      and 18.0  +/-  0.3 mm(3) for 200 mW compared to 10.3  +/-  0.7 mm(3) for its
      fluid only control. Brains treated with 200 mW co-delivery exhibited thermal
      lesions, while 100 mW co-deliveries were associated with preservation of brain
      cytoarchitecture. CONCLUSION: Both lethal and sub-lethal photothermal
      hyperthermia substantially increase the rate of volumetric dispersal in a 1 hour
      CED infusion. This suggests that the FMD co-delivery method could reduce infusion
      times and the number of catheter insertions into the brain during CED procedures.

PMID- 23861186
TI  - A review of propeller flaps for distal lower extremity soft tissue
      reconstruction: Is flap loss too high?
AB  - Soft tissue coverage in the distal lower extremity remains a significant
      challenge. While free flaps are often utilized for larger defects, local
      perforator-based propeller flaps may be ideal for smaller wounds requiring
      coverage. Propeller flaps can provide excellent form and function for both
      traumatic and atraumatic defects with minimal donor site morbidity but can have
      concerning rates of flap loss. We reviewed the literature, identifying 21 studies
      presenting 310 propeller flaps for distal lower extremity reconstruction. Total
      flap necrosis was noted in 5.5% of flaps, with partial necrosis in 11.6%. While
      these flaps do enable transfer of local, healthy tissue to the defect site
      without the need for a microsurgical anastomosis, this rate of flap loss is
      concerning and appropriate patient selection is crucial. This review provides a
      brief history and overview of the clinical application and research into distal
      lower extremity perforator propeller flaps to place this technique into a
      clinical context.

PMID- 23861188
TI  - Characterization of macrolide resistance of Mycoplasma pneumoniae in children in
      Shenzhen, China.
AB  - Macrolide-resistant Mycoplasma pneumoniae (MR-M. pneumoniae) was isolated from
      clinical specimens in Shenzhen, China from November 2010 to July 2011. A
      comparative study was conducted to determine whether macrolides are effective in
      treating patients infected with MR-M. pneumoniae. Of 57 M. pneumoniae strains, 36
      harbored point mutations on A2063G in the 23S ribosomal RNA gene. A total of 36
      (63%) strains were classified as MR-M. pneumonia and 21 (37%) as macrolide
      susceptible M. pneumoniae (MS-M. pneumoniae). The clinical courses of MR-M.
      pneumoniae-infected patients (MR patients) treated with macrolides were compared
      with those of MS-M. pneumoniae-infected patients (MS patients). The patient
      demographics (sex, age), most laboratory findings, and diagnosis did not show
      significant differences between the two groups. The MR patients had higher mean
      total febrile days compared with MS patients (6.56 +/- 6.17 days vs. 3.57 +/-
      3.80 days, P = 0.05). The MR patients were more likely to be have levels of high
      sensitivity C-reactive protein than MS patients (42% (15/36) vs. 14% (3/21), P =
      0.03). Although the febrile period was prolonged in MR patients treated with
      macrolides, the fever resolved even when the initial prescription was unchanged.
      Therefore, these results suggest that macrolides are less effective in MR
      patients than in MS patients.

PMID- 23861187
TI  - Subcutaneous immunoglobulin for primary and secondary immunodeficiencies: an
      evidence-based review.
AB  - BACKGROUND: Substitution with immunoglobulin can be administered intravenously
      (IV) or subcutaneously (SC) to patients with immunodeficiency, but it is not
      clear which route is to be preferred. OBJECTIVE: The aim of this study was to
      compare IV and SC administration of immunoglobulin regarding efficacy, safety,
      health-related quality of life and health economics in patients with primary or
      secondary immunodeficiency. METHOD: PubMed and other databases were searched.
      Reference lists of retrieved articles were scanned and major immunoglobulin
      producers were contacted for additional articles. Randomized and non-randomized
      clinical studies that compared SC with IV immunoglobulin substitution in patients
      with immunodeficiency were included. The validity of the findings in the included
      studies was evaluated and summarized in accordance with the GRADE approach.
      RESULTS: Twenty-five studies were included; two randomized and 17 non-randomized
      studies of patients with primary immunodeficiency, one non-randomized study of
      patients with secondary immunodeficiency and five studies of health economics.
      The quality of evidence as assessed by the GRADE score was found to be moderate
      or low for all outcomes. Both IV and SC administration of immunoglobulin was
      found to be highly effective in preventing serious bacterial infections. IgG
      trough levels were higher with SC immunoglobulin substitution. Both therapy forms
      were concluded to be safe, as no serious adverse event was reported. Minor
      adverse events, consisting of local symptoms that were usually mild, were more
      frequent with SC immunoglobulin substitution. Health-related quality of life
      improved when patients switched from hospital-based IV immunoglobulin
      substitution to SC immunoglobulin substitution at home. The studies that
      evaluated health economics all found that SC administration was considerably more
      cost effective in comparison with IV immunoglobulin substitution. The main
      difference was that the number of lost work or school days was lower in patients
      with SC administration. CONCLUSION: Both SC and IV immunoglobulin substitution
      offer protection from serious bacterial infections and have good safety. On the
      basis of available studies it is not possible to rate one of the two substitution
      modes as superior to the other, at least not regarding efficacy and safety.
      Improvement of health-related quality of life with SC immunoglobulin substitution
      largely seems to be related to home therapy. Studies including patients with
      secondary immunodeficiency were few, as were randomized studies of patients with
      primary immunodeficiency.

PMID- 23861189
TI  - Intrauterine red cell transfusion for anti-Kell isoimmunization in a fetus with
      Glanzmann's thrombasthenia.

PMID- 23861190
TI  - Utility of multi-channel surface electromyography in assessment of focal hand
      dystonia.
AB  - INTRODUCTION: Surface electromyography (SEMG) allows objective assessment and
      guides selection of appropriate treatment in focal hand dystonia (FHD). METHODS:
      Sixteen-channel SEMG obtained during different phases of a writing task was used
      to study timing, activation patterns, and spread of muscle contractions in FHD
      compared with normal controls. Customized software was developed to acquire and
      analyze EMG signals. RESULTS: SEMG of FHD subjects (20) showed "early onset"
      during motor imagery, rapid proximal muscle recruitment, agonist-antagonist co
      contraction involving proximal muscle groups, "delayed offset" after stopping
      writing, higher rectified mean amplitudes, and mirror activity in contralateral
      limb compared with controls (16). Muscle activation latencies were heterogenous
      in FHD. CONCLUSIONS: Anticipation, delayed relaxation, and mirror EMG activation
      were noted in FHD. A clear pattern of muscle activation cannot be ascertained.
      Multi-channel SEMG can aid in objective assessment of temporal-spatial
      distribution of activity and can refine targeted therapies like chemodenervation
      and biofeedback.

PMID- 23861192
TI  - Synthesis, structure and photoluminescence properties of europium-, terbium-, and
      thulium-doped Ca3Bi(PO4)3 phosphors.
AB  - A series of Eu(3+), Tb(3+), Tm(3+) singly and triply doped Ca3Bi(PO4)3 (CBP)
      phosphors were synthesized by solid-state reaction. Their structure and
      photoluminescence (PL) properties were first investigated in detail. Rietveld
      refinement analysis confirmed that the CBP has a cubic unit cell. Its space group
      was determined to be I4[combining macron]3d with cell parameters a = b = c =
      9.941 A and Z = 4. In addition, the Ca3Bi(PO4)3 shows both cation disorder and
      oxygen sublattice disorder. For the CBP:Eu(3+) phosphor, the charge transfer
      bands in the PLE spectra were different at 293 K and 4.3 K, and a model was
      presented to give a possible explanation for this phenomenon. CBP:Eu(3+) shows
      intense red emission due to (5)D0-(7)F2 transition and its integral emission
      intensity and quantum efficiency are higher than the commercial Y2O3:Eu(3+)
      phosphor under irradiation of 397 nm, indicating that the CBP:Eu(3+) phosphor
      might have potential application in the NUV range for solid-state lighting. The
      CBP:Tb(3+) and CBP:Tm(3+) phosphors show intense green and blue emission due to
      (5)D4-(7)F2 transition of the Tb(3+) ions and the (1)D2-(3)F4 transition of the
      Tm(3+) ions, respectively. The energy transfer from the Tb(3+) to Eu(3+) ions was
      also validated by the spectra and decay curves of the Tb(3+) ions. Tunable
      emission colors were obtained by triply doping Eu(3+), Tb(3+) and Tm(3+)
      activators in a single host and adjusting their relative ratio. 

PMID- 23861193
TI  - Journees Andre Collet de la Chiralite (JACC 2012).

PMID- 23861191
TI  - Insula and anterior cingulate GABA levels in posttraumatic stress disorder:
      preliminary findings using magnetic resonance spectroscopy.
AB  - BACKGROUND: Increased reactivity of the insular cortex and decreased activity of
      the dorsal anterior cingulate cortex (ACC) are seen in functional imaging studies
      of posttraumatic stress disorder (PTSD), and may partly explain the persistent
      fear and anxiety proneness that characterize the disorder. A possible
      neurochemical correlate is altered function of the inhibitory neurotransmitter
      gamma-aminobutyric acid (GABA). We report results from what we believe is the
      first study applying proton magnetic resonance spectroscopy ((1) H-MRS) to
      measure brain GABA in PTSD. METHODS: Thirteen adults with DSM-IV PTSD and 13
      matched healthy control subjects underwent single voxel (1) H-MRS at 4 Tesla.
      GABA was measured in the right anterior insula and dorsal ACC, using Mescher
      Garwood Point-Resolved Echo Spectroscopy Sequence (MEGAPRESS) spectral editing.
      Subjects were interviewed with the Structured Clinical Interview for DSM-IV and
      the Clinician Administered PTSD Scale, and also completed the State and Trait
      Anxiety Inventory. RESULTS: Insula GABA was significantly lower in PTSD subjects
      than in controls, and dorsal ACC GABA did not differ significantly between the
      groups. Insula GABA was not significantly associated with severity of PTSD
      symptoms. However, lower insula GABA was associated with significantly higher
      state and trait anxiety in the subject sample as a whole. CONCLUSIONS: PTSD is
      associated with reduced GABA in the right anterior insula. This preliminary
      evidence of the (1) H-MRS GABA metabolite as a possible biomarker of PTSD
      encourages replication in larger samples and examination of relations with
      symptom dimensions. Future studies also should examine whether insula GABA is a
      marker of anxiety proneness, cutting across clinical diagnostic categories.

PMID- 23861194
TI  - Chiroptical properties of carbo[6]helicene derivatives bearing extended pi
      conjugated cyano substituents.
AB  - New carbo[6]helicene derivatives grafted with pi-conjugated cyano-phenyl arms
      were synthesized in enantiopure forms and their pi-conjugation examined by UV-vis
      spectroscopy. The influence of the pi-conjugation on the circular dichroism
      spectra and molar rotations is discussed based on comparing experimental data
      with results from quantum-chemical calculations. The results highlight the fact
      that increasing the spatial extension of the pi-system in a helicene molecule is
      an efficient way of increasing its molar rotation.

PMID- 23861196
TI  - Trends in post-mastectomy reconstruction: a SEER database analysis.
AB  - BACKGROUND AND OBJECTIVES: This study was performed to investigate recent trends
      and factors associated with immediate breast reconstruction (IBR) using a large
      population-based registry. We hypothesized that rates of IBR have increased since
      passage of the Women's Health and Cancer Rights Act of 1998. METHODS: The SEER
      (surveillance, epidemiology and end results) database was used to evaluate Stage
      I-III breast cancer (BC) patients who underwent total mastectomy from 1998 to
      2008. Univariate and multivariate analyses were performed to study predictors of
      IBR. RESULTS: Of 112,348 patients with BC treated by mastectomy 18,001 (16%) had
      IBR. Rates of IBR increased significantly from 1998 to 2008 (P < 0.0001). Use of
      IBR significantly decreased as patient age increased (P < 0.0001), as stage
      increased (P < 0.0001), and as the number of positive lymph nodes increased (P <
      0.0001). Estrogen receptor+/progesterone receptor+ (ER+/PR+) patients had
      significantly higher IBR rates than ER-/PR-patients (P < 0.0001). IBR was used in
      3,615 of 25,823 (14.0%) of patients having post-mastectomy radiation (XRT) and in
      14,188 of 86,513 (16.4%) of those not having XRT (P < 0.0001). CONCLUSIONS: The
      utilization of IBR has increased significantly over the last decade. IBR was
      found to be significantly associated with age, race, geographical region, stage,
      ER, grade, LN status, and XRT (P < 0.0001).

PMID- 23861198
TI  - A trial of proficiency of nerve conduction: greater standardization still needed.
AB  - INTRODUCTION: The aim of this study was to test the proficiency (accuracy among
      evaluators) of measured attributes of nerve conduction (NC). METHODS: Expert
      clinical neurophysiologists, without instruction or consensus development, from 4
      different medical centers, independently assessed 8 attributes of NC in 24
      patients with diabetes mellitus (DM) on consecutive days. RESULTS: No significant
      intraobserver differences between days 1 and 2 were found, but significant
      interobserver differences were seen. Use of standard reference values did not
      correct for these observed differences. CONCLUSIONS: Interobserver variability
      was attributed to differences in performance of NC. It was of sufficient
      magnitude that it is of concern for the conduct of therapeutic trials. To deal
      with interrater variability in therapeutic trials, the same electromyographers
      should perform all NC assessments of individual patients or, preferably, NC
      procedures should be more standardized. A further trial is needed to test whether
      such standardization would eliminate interobserver variability.

PMID- 23861199
TI  - Interaction study of acetylcholinestrase inhibitors on pharmacokinetics of
      memantine in rat plasma by HPLC-fluorescence method.
AB  - The present study aims to investigate the possibility of interaction of donepezil
      (DP) and galantamine (GAL) as acetylcholinestrase inhibitors, on memantine (MT)
      hydrochloride in rat plasma by HPLC-fluorescence detection. The separation of MT
      was achieved within 12 min without interference of DP and GAL on the
      chromatogram. MT levels in rat plasma with a single administration of MT (2.5
      mg/kg, i.p.) and those with a co-administration of DP (5.0 mg/kg, i.p.) and GAL
      (3 mg/kg, i.p.) were monitored. MT concentrations determined in rat plasma ranged
      from 10.0 to 245.6 ng/mL. Significant difference was observed in the behavior of
      MT with a co-administration of DP, while no significant difference was observed
      with a co-administration of GAL.

PMID- 23861200
TI  - Does experience matter in sarcoma surgery?

PMID- 23861201
TI  - Never let them see you cry: self-presentation as a moderator of the relationship
      between exclusion and self-esteem.
AB  - A debate exists concerning whether exclusion harms self-esteem. We hypothesized
      that social exclusion does harm self-esteem, but that this effect is evident only
      when self-presentational concerns to "appear fine" are minimal or people are
      unable to alter their report of self-esteem. In the first three studies,
      participants' explicit and implicit self-esteem were measured following an
      exclusion or comparison condition where self-presentational pressures were likely
      high. Because respondents can easily control their reports on explicit measures,
      but not on implicit ones, we hypothesized that exclusion would result in lower
      self-esteem only when implicit measures were used. Results confirmed this
      hypothesis. In the final study, self-presentational concerns were directly
      manipulated. When self-presentational concerns were high, only implicit self
      esteem was lowered by exclusion. But, when such concerns were low, this impact on
      self-esteem was seen on implicit and explicit measures. Implications for the
      sociometer hypothesis and the recent self-esteem debate are discussed. 

PMID- 23861202
TI  - Leaving a legacy neutralizes negative effects of death anxiety on creativity.
AB  - Mortality salience (MS) can lead to a paralyzing terror, and to cope with this,
      people strive for literal or symbolic immortality. As MS leads to conformity and
      narrow-mindedness, we predicted that MS would lead to lower creativity, unless
      creativity itself could lead to leaving a legacy and thus symbolic immortality.
      We show that this pattern holds (Experiment 1), but only when creativity is
      socially valued (Experiment 2). Finally, especially individualistic people are
      more creative under MS when they can leave a legacy than when they cannot, and
      high originality predicts subsequent accessibility of death thoughts (Experiment
      3). Implications are discussed. 

PMID- 23861203
TI  - Variation in chitotriosidase values measured on simultaneous samples by two
      commercial laboratories.

PMID- 23861204
TI  - User cost of Caesarean section: case study of Bunia, Democratic Republic of
      Congo.
AB  - The study estimated the user cost of Caesarean section (CS), a major component of
      emergency obstetric care (EmOC), in a post conflict situation in Bunia, DR Congo,
      2008. A case control study used a structured questionnaire to compare women who
      had a CS (cases) with women who had a vaginal delivery (controls). Service
      information was recorded in 20 facilities providing obstetric care. Maternal and
      perinatal deaths, including those outside health facilities, were recorded and
      verified. The user cost of CS was estimated at four hospitals, one of them
      managed by an international non-governmental organization offering EmOC free of
      charge, compared to the user cost of women who had a vaginal delivery. Among
      paying users, the mean healthcare cost was $US68.0 for CS and $US12.1 for vaginal
      delivery; mean transport cost to and from the hospital was $US11.7 for cases and
      $US3.2 for controls. The mean monthly family income was $US75.5. The user cost of
      CS placed an important financial burden on patients and their families. During
      transition from humanitarian to developmental assistance, donors and the State
      should shore up the EmOC budget to avoid an increase in maternal and perinatal
      mortality.

PMID- 23861205
TI  - Enantioselective synthesis and antimicrobial activities of tetrahydro-beta
      carboline diketopiperazines.
AB  - A series of single isomers tetrahydro-beta-carboline diketopiperazines were
      stereoselectively synthesized starting from l-tryptophan methyl ester
      hydrochloride and six aldehydes through a four-step reaction including Pictet
      Spengler reaction, crystallization-induced asymmetric transformations (CIAT),
      Schotten-Baumann reaction, and intramolecular ester amidation. The chemical
      structures were characterized by nuclear magnetic resonance (NMR) and elemental
      analysis, among which two compounds were determined by x-ray single crystal
      diffraction. Moreover, antimicrobial activities of all the compounds were also
      tested.

PMID- 23861206
TI  - Triple A syndrome in Japan.
AB  - INTRODUCTION: Triple A syndrome is an autosomal recessive disease, characterized
      by esophageal achalasia, alacrima, and adrenal insufficiency, as well as
      involvement of the central, peripheral, and autonomic nervous systems. This
      disease mimics amyotrophic lateral sclerosis in some patients. The causative gene
      encodes ALADIN, a nuclear pore complex (NPC) component. Only 5 patients have been
      reported in Japan. METHODS: We conducted the first nationwide survey of triple A
      syndrome. Identified mutants were expressed as GFP-fusion proteins in cultured
      cells. RESULTS: Two new patients were identified, and 1 had a novel mutation
      (p.Ser182fsX19). All mutant proteins tested were mislocalized from NPC to
      cytoplasm. CONCLUSIONS: The most consistent neurological manifestation of triple
      A syndrome in Japanese patients was progressive bulbospinal muscular atrophy with
      both upper and lower motor neuron involvement, which mimicked motor neuron
      disease, similar to that seen in patients in Western countries. The
      identification of the new patients suggests that more cases are undiagnosed in
      Japan.

PMID- 23861207
TI  - Early expression of the type III secretion system of Parachlamydia acanthamoebae
      during a replicative cycle within its natural host cell Acanthamoeba castellanii.
AB  - The type three secretion system (T3SS) operons of Chlamydiales bacteria are
      distributed in different clusters along their chromosomes and are conserved at
      both the level of sequence and genetic organization. A complete characterization
      of the temporal expression of multiple T3SS components at the transcriptional and
      protein levels has been performed in Parachlamydia acanthamoebae, replicating in
      its natural host cell Acanthamoeba castellanii. The T3SS components were
      classified in four different temporal clusters depending on their pattern of
      expression during the early, mid- and late phases of the infectious cycle. The
      putative T3SS transcription units predicted in Parachlamydia are similar to those
      described in Chlamydia trachomatis, suggesting that T3SS units of transcriptional
      expression are highly conserved among Chlamydiales bacteria. The maximal
      expression and activation of the T3SS of Parachlamydia occurred during the early
      to mid-phase of the infectious cycle corresponding to a critical phase during
      which the intracellular bacterium has (1) to evade and/or block the lytic pathway
      of the amoeba, (2) to differentiate from elementary bodies (EBs) to reticulate
      bodies (RBs), and (3) to modulate the maturation of its vacuole to create a
      replicative niche able to sustain efficient bacterial growth. 

PMID- 23861210
TI  - Arthur H. Whiteley (1916-2013).

PMID- 23861212
TI  - Mannose binding lectin and mannose binding lectin-associated serine protease-2
      genes polymorphisms in human T-lymphotropic virus infection.
AB  - Variations in genes involved in the immune response pathways may influence the
      interaction between viruses (such as Human T-lymphotropic virus, HTLV-1) and the
      host. The mannose binding lectin (MBL) and its associated serine protease type 2
      (MASP-2) promote the activation of the lectin pathway of the complement system.
      As the interaction of complement system with HTLV-1 is not well understood, the
      MBL2 promoter/exon 1 polymorphisms and a MASP2 missense polymorphism were
      examined in a Northeast Brazilian population, looking for a possible relationship
      between these variations and the susceptibility to HTLV-1 infection. The present
      study describes an association between a polymorphism in the MASP2 gene and
      susceptibility to HTLV-1 infection, and provides further evidence of an
      association between the MBL2 gene and HTLV-1 infection. These findings suggest an
      important role of the complement system activation, via the lectin pathway, in
      the susceptibility to HTLV-1 infection.

PMID- 23861213
TI  - Stent-assisted embolization of recurrent or residual intracranial aneurysms.
AB  - INTRODUCTION: Intracranial stents have theoretical advantages in the treatment of
      wide-necked intracranial aneurysms, but the usability of intracranial stents in
      the retreatment of recurrent intracranial aneurysms is relatively unknown. In
      this study, we aim to evaluate the safety and efficacy of stent-assisted
      embolization in the retreatment of recurrent or residual intracranial aneurysms.
      METHODS: Retrospective evaluation was carried out for 55 consecutive patients (17
      men and 38 women; mean age 51.5 years), with 56 recurrent or residual
      intracranial aneurysms electively retreated with stent-assisted embolization.
      RESULTS: The technical success rate was 91% (50/55 patients). Procedural
      complications were encountered with six patients (11%). Angiographic and clinical
      follow-up data were available for 51 patients (93%), with a mean follow-up period
      of 28.1 months. No rebleedings were encountered during the study period. The
      clinical outcome was favorable in 50 patients (91%), with a Glasgow Outcome Score
      of 4 (N = 14) or 5 (N = 36) at the end of the study period. Poor clinical outcome
      correlated with very large (>2 cm) total aneurysm size (P = 0.002), large (>10
      mm) recurrent aneurysm size (P = 0.011), and occurrence of periprocedural
      complications (P < 0.001). CONCLUSION: Stent-assisted coil embolization is
      beneficial for the retreatment of wide-necked recurrent or residual intracranial
      aneurysms, but stability and permanent occlusion of the recurrent aneurysm is
      unlikely if the aneurysm exceeds 2 cm in diameter, the recurrent diameter of the
      aneurysm exceeds 10 mm, or if mass effect is present with the recurrent aneurysm.

PMID- 23861214
TI  - Decreased expression of microRNA-625 is associated with tumor metastasis and poor
      prognosis in patients with colorectal cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) play an essential role in colorectal cancer (CRC)
      development and progression. Aberrant miR-625 expression has been reported in
      several cancers. However, the clinical significance of miR-625 in human CRC has
      not been addressed. METHODS: miR-625 expression was determined in 96 pairs of
      primary CRC and their corresponding adjacent nontumor tissues by quantitative
      reverse transcriptase-polymerase chain reaction. Associations of miR-625
      expression with demographic and clinicopathologic features were determined.
      Additionally, the effects of ectopic expression of miR-625 on cell migration and
      invasion were investigated in vitro and in vivo. RESULTS: miR-625 was
      significantly downregulated in CRC tissues and cell lines. In addition, the
      decreased expression of miR-625 was positively associated with advanced lymph
      node metastasis (P = 0.038), liver metastasis (P = 0.031), poor overall survival
      (P = 0.002), and an unfavorable prognosis for CRC patients, as determined through
      a multivariate analysis (P = 0.034). Moreover, functional assays demonstrated
      that ectopic miR-625 expression inhibits the invasion and migration of HCT116 CRC
      cells both in vitro and in vivo. CONCLUSIONS: Our results suggest that miR-625
      may serve as an efficient clinical biomarker and a therapeutic tool for the
      inhibition of metastasis in CRC.

PMID- 23861215
TI  - Cortico-limbic responses to masked affective faces across ptsd, panic disorder,
      and specific phobia.
AB  - BACKGROUND: Exaggerated amygdala and reduced ventromedial prefrontal cortex
      (vmPFC) responsiveness during emotional processing have been reported in studies
      examining individual anxiety disorders. Studies are needed, however, which
      directly compare activation of amygdalo-cortical circuitry across multiple
      anxiety disorders within the same study. Here we compared cortico-limbic
      neurocircuitry across three different anxiety disorders using a well-validated
      emotional probe task. METHODS: Sixty-five adult volunteers, including 22 healthy
      controls (HC) and participants meeting DSM-IV criteria for either posttraumatic
      stress disorder (14 PTSD), panic disorder (14 PD), or specific animal phobia (15
      SP), underwent functional magnetic resonance imaging (fMRI) at 3 T while
      passively viewing backward-masked images of faces expressing fear, happy, and
      neutral emotions. RESULTS: A group comprising all three anxiety disorders showed
      greater activation within the left amygdala and reduced activation within the
      vmPFC compared to the HC group during the masked fear versus neutral condition.
      Pairwise group comparisons showed that amygdala activation only reached
      significance for the PTSD versus HCs, whereas decreased vmPFC was only evident
      for SP and PD groups versus the HC group. Furthermore, activation did not differ
      among the anxiety groups when contrasted directly with one another. A similar
      pattern was observed for masked happy versus neutral faces. CONCLUSIONS:
      Exclusive of specific diagnostic category, anxiety disorders were generally
      associated with increased activation of the amygdala and reduced activation
      within vmPFC. Categorical distinctions were generally weak or not observed and
      suggest that functional differences may reflect the magnitude of responses within
      a common neurocircuitry across disorders rather than activation of distinct
      systems.

PMID- 23861216
TI  - Tissue iron evaluation in chronically transfused children shows significant
      levels of iron loading at a very young age.
AB  - Chronic blood transfusions start at a very young age in subjects with transfusion
      dependent anemias, the majority of whom have hereditary anemias. To understand
      how rapidly iron overload develops, we retrospectively reviewed 308 MRIs for
      evaluation of liver, pancreatic, or cardiac iron in 125 subjects less than 10
      years old. Median age at first MRI evaluation was 6.0 years. Median liver iron
      concentrations in patients less than 3.5 years old were 14 and 13 mg/g dry weight
      in thalassemia major (TM) and Diamond-Blackfan anemia (DBA) patients,
      respectively. At time of first MRI, pancreatic iron was markedly elevated (> 100
      Hz) in DBA patients, and cardiac iron ( R2* >50 Hz) was present in 5/112 subjects
      (4.5%), including a 2.5 years old subject with DBA. Five of 14 patients (38%)
      with congenital dyserythropoietic anemia (CDA) developed excess cardiac iron
      before their 10th birthday. Thus, clinically significant hepatic and cardiac iron
      accumulation occurs at an early age in patients on chronic transfusions,
      particularly in those with ineffective or absent erythropoiesis, such as DBA,
      CDA, and TM, who are at higher risk for iron cardiomyopathy. Performing MRI for
      iron evaluation in the liver, heart, and pancreas as early as feasible,
      particularly in those conditions in which there is suppressed bone marrow
      activity is very important in the management of iron loaded children in order to
      prescribe appropriate chelation to prevent long-term sequelae. .

PMID- 23861217
TI  - Cultural camouflage--a critical study of how artefacts are camouflaged and mental
      health policy subverted.
AB  - This study identifies hidden artefacts in a public organisation. In contrast to
      earlier studies, it focuses on artefacts as concealing rather than conveying
      meaning. Negligent behaviour caused by an unpopular culture was recognised in
      five psychiatric wards at a Swedish university hospital. Data comprising
      observations (87 h) and interviews (n = 60) were collected over a period of 48
      months (2008-2011). Four different items used in everyday work representing a
      deeper meaning of the organisation were identified during the observations. The
      items selected were work attire, nametags, keys and restraint beds. These were
      considered particularly promising when it came to the aim of the study, namely,
      to find out how artefacts are camouflaged. The observations and the interviews
      revealed that these were controversial and contested artefacts in the
      organisation. The study uses the term 'cultural camouflage' for behaviour that
      ignores and consciously conceals symbols that have negative values. This concept
      contrasts with previous research that shows how artefacts are emphasised and how
      they contribute to the character of the activity in a transparent way.
      Conservative and backward-looking behaviour among staff provided one explanation
      as to why artefacts were concealed. Another was the need to establish harmonious
      internal interactions.

PMID- 23861218
TI  - Genetic variations in the PRKAA1 and ZBTB20 genes and gastric cancer
      susceptibility in a Korean population.
AB  - A recent genome-wide association study (GWAS) identified new susceptibility
      single-nucleotide polymorphisms (SNPs) rs13361707 (PRKAA1 and PTGER4 gene on
      5p13.1) and rs9841504 (ZBTB20 gene on 3q13.31) that were significantly associated
      with non-cardia gastric cancer. The aim of this study was to determine whether
      rs13361707 and rs9841504 polymorphisms are associated with the risk of gastric
      cancer in a Korean population. We conducted a large-scale case-control study of
      3245 gastric cancer patients and 1700 controls. The allele frequencies for
      rs13361707 C and rs9841504 G were 53.5% and 18.3% among gastric cancer cases,
      compared with 47.1% and 17.2% among controls, respectively. We found that
      rs13361707 TC and CC genotypes were associated with increased risk for gastric
      cancer (odds ratios [OR] = 1.29; 95% confidence interval [CI] = 1.11-1.51 for TC
      vs. TT and 1.68; 1.41-2.01 for CC vs. TT). However, we found no significant
      association between rs9841504 and gastric cancer risk (OR = 1.11; 0.97-1.28 for
      CG vs. CC; OR = 1.09; 0.77-1.53 for GG vs. CC). We observed no significant
      interactions between rs13361707 and rs9841504 polymorphisms and age, gender,
      smoking habit, alcohol consumption, and clinicopathologic characteristics such as
      anatomical tumor location and histological type. Our study showed that the
      rs13361707 polymorphism was associated with increased risk of gastric cancer in a
      Korean population. This finding provides further evidence that genetic variant of
      PRKAA1 and PTGER4 genes may contribute to the gastric carcinogenesis. However, we
      found no association between rs9841504 and gastric cancer risk.

PMID- 23861219
TI  - Motor unit potential change with contraction level: a concentric macro
      electromyography study.
AB  - INTRODUCTION: Motor unit action potential (MUAP) reference values are usually
      given per muscle and age group. Our aim was to evaluate the change in MUAP size
      at different contraction levels using the concentric macro (ConMac) EMG
      technique. METHODS: ConMac needles were used to record the electrode cannula MUAP
      and measure its amplitude and area during weak, moderate, and strong muscle
      contractions. RESULTS: MUAP area and amplitude gradually increased from weak to
      strong contraction levels in all muscles studied. MUAP amplitudes were larger in
      distal than in proximal muscles, likely because of a higher fiber density
      distally. CONCLUSIONS: MUAP normal values in the literature per muscle do not
      take into account the contraction level at which they were recorded and can
      misrepresent the interpretation of normal. Concentric macro EMG is a simple and
      useful complement to routine EMG studies and yields additional information on
      MUAP neurophysiology.

PMID- 23861220
TI  - Hepatitis C virus genotype 4 in Southern and Central Spain does not originate
      from recent foreign migration waves.
AB  - Hepatitis C virus genotype 4 (HCV-4) is highly prevalent in Spain, but the
      information on the molecular characterization of HCV-4 in this region is scarce.
      Due to this, the molecular characteristics and the evolution of HCV-4 infection
      in Seville were analyzed (Southern Spain) and compared them with samples from
      Madrid. HCV genotype was determined by LIPA 2.0 assay and confirmed by sequence
      analysis of NS5B. Phylogenetic tree was estimated by MEGA 5.10. Bayesian
      coalescent-based methods were used to estimate the substitution rate and the age
      of the most recent common ancestor (MRCA). In the phylogenetic analysis of 50
      NS5B HCV-4 from Seville and 11 from Madrid, 2 clusters were distinguished: The
      first cluster (HCV-4a) included 48% of the sequences from Seville and 9% of
      sequences from Madrid. The second cluster included the remaining sequences
      belonging to HCV-4d. The mean estimated substitution rate was 2.39 * 10(-3) for
      HCV-4a and 1.81 * 10(-3) for HCV-4d for Seville and 2.32 * 10(-3) for HCV-4d from
      Madrid. The date for MRCA was estimated to be around 1981-1984 for HCV-4 from
      Seville. The dates for MRCA were dated before the recent flow of immigration in
      Spain. Therefore, the results presented in this study argues against the
      possibility of a foreign introduction of the HCV-4 from other regions with high
      prevalence, at least during the last two, decades in which there was a great flow
      of immigrants. Additionally, an unusual high prevalence of subtype 4a was
      observed in Seville.

PMID- 23861221
TI  - Estimated frequency of antiphospholipid antibodies in patients with pregnancy
      morbidity, stroke, myocardial infarction, and deep vein thrombosis: a critical
      review of the literature.
AB  - OBJECTIVE: Antiphospholipid Syndrome Alliance For Clinical Trials and
      International Networking (APS ACTION) is an international research network
      devoted to conducting well-designed clinical trials in persistently
      antiphospholipid antibody (aPL)-positive patients. One of the first needs of APS
      ACTION was to know the true aPL frequency in patients with pregnancy morbidity
      (PM), stroke (ST), myocardial infarction (MI), and deep venous thrombosis (DVT).
      METHODS: The search for "aPL" and multiple keywords regarding the outcomes of
      interest was completed in PubMed. The median frequency for positive aPL tests
      (lupus anticoagulant, antibody against cardiolipin [aCL], and antibody against
      beta(2)-glycoprotein I [anti-beta(2)GPI]) was calculated for each outcome and was
      used to estimate the overall aPL frequency. RESULTS: Based on the analysis of 120
      full-text papers, the overall aPL frequency was estimated as 6% for PM, 13.5% for
      ST, 11% for MI, and 9.5% for DVT. Limitations of the literature were that 60% of
      the papers were published before 2000, all 3 criteria aPL tests were performed in
      only 11% of the papers, 36% of papers used a low-titer aCL cutoff, anti
      beta(2)GPI cutoff was quite heterogeneous, aPL confirmation was performed in only
      one-fifth of papers, and the study design was retrospective in nearly half of the
      papers. CONCLUSION: It is difficult to determine the frequency of a "clinically
      significant aPL profile" in patients with aPL-related clinical outcomes due to
      the lack of robust data. Our best estimates of the incidence of aPL-associated
      events should be confirmed with appropriately designed population studies.

PMID- 23861222
TI  - Inhibitions of epithelial to mesenchymal transition and cancer stem cells-like
      properties are involved in miR-148a-mediated anti-metastasis of hepatocellular
      carcinoma.
AB  - The epithelial-mesenchymal transition (EMT) and acquisition of cancer stem cells
      (CSCs)-like properties are essential steps in the metastasis and postsurgical
      recurrence of hepatocellular carcinomas (HCCs). The molecular mechanisms
      involved, however, remain obscure. As determined by an miRNA microarray analysis,
      there was lower expression of miR-148a in poorly differentiated HCC tissues
      relative to well-differentiated HCC tissues. MHCC97H and MHCC97L (HCC cells with
      migratory capacity) and HCC tissues with various differentiation status were
      selected for further investigation. The results showed that miR-148a levels
      inversely correlated with the differentiation status of HCC tissues. In MHCC97H
      and MHCC97L cells, over-expression of miR-148a blocked the EMT process,
      attenuated the expression of CD90 and CD44 (biomarkers for liver cancer stem
      cells), and inhibited their migratory capacity. Via TargetScan and microRNA.org
      algorithms, miR-148a was predicted to bind to the Wnt1 mRNA 3'-UTR. Wnt1 was
      confirmed as a target gene of miR-148a in HCC cells, and the Wnt signal pathway
      was determined to be involved in the miR-148a-mediated inhibition of EMT and CSCs
      like properties of MHCC97H cells. Moreover, the expression of miR-148a in
      nonmetastatic HCC tissues was higher than that in metastatic HCC tissues. The
      results suggest that miR-148a inhibits the metastasis of HCCs by blocking EMT and
      CSCs-like properties through effects on the Wnt signaling pathway.

PMID- 23861223
TI  - Genome wide SNP array identified multiple mechanisms of genetic changes in
      Waldenstrom macroglobulinemia.
AB  - SNP array (SNPa) was developed to detect copy number alteration (CNA) and loss of
      heterozygosity (LOH) without copy number changes, CN-LOH. We aimed to identify
      novel genomic aberrations using SNPa in 31 WM with paired samples. Methylation
      status and mutation were analyzed on target genes. A total of 61 genetic
      aberrations were observed, 58 CNA (33 gains, 25 losses) in 58% of patients and CN
      LOH in 6% of patients. The CNA were widely distributed throughout the genome,
      including 12 recurrent regions and identified new cryptic clonal chromosomal
      lesions that were mapped. Gene set expression analysis demonstrated a
      relationship between either deletion 6q or gain of chromosome 4 and alteration of
      gene expression profiling. We then studied methylation status and sought for
      mutations in altered regions on target genes. We observed methylation of DLEU7 on
      chromosome 13 in all patients (n = 12) with WM, and mutations of CD79B/CD79A
      genes (17q region), a key component of the BCR pathway, in 15% of cases. Most
      importantly, higher frequency of >=3 CNA was observed in symptomatic WM. In
      conclusion, this study expands the view of the genomic complexity of WM,
      especially in symptomatic WM, including a potentially new mechanism of gene
      dysfunction, acquired uniparental disomy/CN-LOH. Finally, we have identified new
      potential target genes in WM, such as DLEU7 and CD79A/B.

PMID- 23861224
TI  - Role of allelic variants of FK506-binding protein 51 (FKBP5) gene in the
      development of anxiety disorders.
AB  - BACKGROUND: Anxiety disorders exhibit remarkably high rates of comorbidity with
      major depressive disorder (MDD). Mood and anxiety disorders are considered stress
      related diseases. Genetic variations in the co-chaperone FK506-binding protein
      51, FKBP5, which modulates the function of glucocorticoid receptors, have been
      associated with an increased risk for the development of posttraumatic stress
      disorder, but data regarding its role in MDD are controversial. The aims of this
      study were to clarify the role of the FKBP5 gene in depression and anxiety
      disorders through a case-control study and an association study with personality
      traits using the Temperament and Character Inventory (TCI) in healthy subjects.
      METHODS: Six hundred fifty-seven MDD patients, with or without an anxiety
      disorder in comorbidity, and 462 healthy volunteers were enrolled in the study.
      Two hundred fifty-six controls agreed to fill out the TCI. RESULTS: The results
      showed that the T allele of rs1360780 was more frequent among the patients
      affected by MDD with a comorbidity of anxiety disorders, compared to those
      without (P < .001). Among the controls, we found that the T allele more often
      exhibited personality traits associated with an increased vulnerability to
      anxiety. CONCLUSIONS: These results support the hypothesis that allelic variants
      of FKBP5 are a risk factor for anxiety disorders. The identification of genetic
      variants involved in anxiety may have implications for the optimization of
      therapeutic interventions.

PMID- 23861225
TI  - The impact factor.

PMID- 23861227
TI  - beta-Carotene, alpha-tocopherol and ascorbic acid: differential profile of
      antioxidant, inflammatory status and regulation of gene expression in human
      mononuclear cells of diabetic donors.
AB  - BACKGROUND: Diabetic patients are exposed to increased oxidative stress due to
      several mechanisms, mainly hyperglycaemia. Pathological processes, such as those
      in type 1 diabetes, include diminished activity of the antioxidant defense
      system(s) or excessive oxidative generation resulting in an oxidative/antioxidant
      imbalance and development of oxidative stress. METHODS: The purpose of this study
      was to evaluate the production of reactive oxygen species (ROS)
      (chemiluminescence) and reduction capacity (MTT dye reduction), the expression of
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, superoxide
      dismutase and catalase using quantitative reverse-transcriptase polymerase chain
      reaction, and the levels of cytokines [interleukin (IL)-6, tumour necrosis factor
      alpha, IL-8, IL-10 and IL-4] by sandwich enzyme-linked immunosorbent assay in
      mononuclear cells from non-diabetic and diabetic donors treated with a vitamin
      complex (ascorbic acid, beta-carotene and alpha-tocopherol) in two different
      concentrations ([A] = ascorbic acid = 0.08 uM, alpha-tocopherol = 0.04 uM, beta
      carotene = 0.0008 uM and [20A] = ascorbic acid = 1.6 uM, alpha-tocopherol = 0.82
      uM, beta-carotene = 0.016 uM). RESULTS: Concentration [A] was antioxidant
      reducing ROS production, expression of NADPH oxidase subunits and pro
      inflammatory cytokines while raising the expression of antioxidant enzymes and
      reducing pro-inflammatory cytokines in both groups. Concentration [20A] was pro
      oxidant by raising ROS production, NADPH oxidase subunits and pro-inflammatory
      cytokines and reducing antioxidant enzymes and anti-inflammatory cytokines in the
      non-diabetic group but antioxidant in cells of type 1 diabetic patients by
      raising antioxidant enzymes and anti-inflammatory cytokines and reducing pro
      inflammatory cytokines. CONCLUSION: The vitamin complex has a dual effect, pro
      oxidant and antioxidant, being also dose dependent with different profiles of
      cells of non-diabetic and type 1 diabetic patients.

PMID- 23861228
TI  - Calcium-mediated secondary cross-linking of bisphosphonated oligo(poly(ethylene
      glycol) fumarate) hydrogels.
AB  - This study demonstrates, for the first time, that synthetic PEG-based hydrogels
      can be cross-linked reversibly by calcium upon functionalization of the polymer
      backbone with bisphosphonate groups (BPs) that allow for the formation of strong
      coordination bonds with divalent metal ions such as Mg(2+) and Ca(2+). More
      specifically, it is shown that BP-functionalized hydrogels can be shaped by
      providing calcium ions as reversible physical cross-linkers.

PMID- 23861229
TI  - Statistical analysis of human papillomavirus in a subset of upper aerodigestive
      tract tumors.
AB  - Human papilloma virus (HPV) has been detected in some upper aerodigestive tract
      tumors, but the correlation between HPV and these tumors is not well understood.
      There is also some controversy regarding this correlation because a large
      variation in the prevalence of HPV in these tumors has been reported. To discuss
      the impact of HPV infection on upper aerodigestive tract tumors, this review
      estimated systematically the prevalence and risk of HPV in upper aerodigestive
      tract tumors from studies published between 1982 and 2012. In total, 418 articles
      were selected, which included 273 studies on the head and neck and 145 studies on
      esophageal squamous cell carcinoma. The overall prevalence of HPV in the 5,467
      head and neck squamous cell carcinoma specimens was 36.3%. HPV was detected more
      frequently in the Americas (40%), than in Asia (38.6%), Europe (32%), or others
      regions (30.5%). The prevalence of HPV was significantly higher in oropharyngeal
      (48.5%) than in oral (32.5%), laryngeal (30.7%), and unselected head and neck
      squamous cell carcinoma (33.3%) (P < 0.001). The pooled prevalence of HPV in the
      6,912 esophageal squamous cell carcinoma cases was 38.9% and it was significantly
      higher in China (44%) versus other regions (31.3%) (P < 0.05). Meta-analysis
      showed that head and neck and esophageal squamous cell carcinoma are associated
      with HPV infection (combined OR: 3.58, OR for head and neck and esophageal
      squamous cell carcinoma: 4.20). These findings suggest that HPV might be linked
      etiologically to the development of some upper aerodigestive tract tumors.

PMID- 23861230
TI  - Early changes of muscle insulin-like growth factor-1 and myostatin gene
      expression in gastric cancer patients.
AB  - INTRODUCTION: Cachexia increases morbidity and mortality of cancer patients. The
      progressive loss of muscle mass negatively affects physical function and quality
      of life. We previously showed reduced muscle insulin-like growth factor-1 (IGF-1)
      expression and enhanced myostatin signaling in tumor-bearing animals. This study
      was aimed at investigating whether similar perturbations occur in gastric cancer
      patients. METHODS: Early perturbations of myostatin and IGF-1 signaling
      (including the expression of muscle-specific ubiquitin ligases) were investigated
      in 16 gastric cancer patients and in 6 controls by analyzing muscle mRNA
      expression with semiquantitative reverse transcriptase polymerase chain reaction
      (PCR) and real-time PCR. RESULTS: In gastric cancer patients, muscle mRNA levels
      for IGF-1, myostatin, and atrogin-1 were reduced irrespective of weight loss
      (<=5% or >5%), whereas MuRF1 expression was unchanged. CONCLUSIONS: IGF-1 and
      myostatin mRNA levels are downregulated in gastric cancer patients who have
      minimal or no weight loss. These early alterations are particularly relevant in
      order to devise preventive and therapeutic strategies for cancer cachexia.

PMID- 23861231
TI  - Alkyne phosphonites for sequential azide-azide couplings.

PMID- 23861232
TI  - Clinical and health care use characteristics of patients newly starting
      allopurinol, febuxostat, and colchicine for the treatment of gout.
AB  - OBJECTIVE: Gout is a common form of inflammatory arthritis with an increasing
      prevalence in developed countries. It is well known that many patients with gout
      have significant comorbidities and high health care utilization. We aimed to
      describe the clinical characteristics and health care utilization patterns in
      patients with gout who were newly prescribed allopurinol, febuxostat, or
      colchicine. METHODS: We used US insurance claims data (2009-2011) to conduct a
      population-based cohort study. RESULTS: There were 25,051 allopurinol, 4,288
      febuxostat, and 6,238 colchicine initiators. The mean age was 53 years and 83-87%
      were men. More than one-half of the patients had hypertension and hyperlipidemia,
      20% had diabetes mellitus, and 10% had cardiovascular disease. The mean uric acid
      level was similar across the groups at baseline, ranging from 8.1-8.5 mg/dl.
      Compared with allopurinol or colchicine initiators, febuxostat initiators had
      more comorbidities and greater health care utilization, including outpatient,
      inpatient, or emergency room visits, both at baseline and during followup. Use of
      gout-related drugs such as opioids, steroids, and nonsteroidal antiinflammatory
      drugs was most common in febuxostat initiators and least common in colchicine
      initiators. The median daily doses at both the start and end of treatment were
      300 mg for allopurinol, 40 mg for febuxostat, and 1.2 mg for colchicine. The
      doses of allopurinol and febuxostat were rarely increased during followup.
      CONCLUSION: Patients who started allopurinol, febuxostat, or colchicine for gout
      generally had hyperuricemia and multiple comorbidities. Febuxostat initiators had
      more comorbidities and greater use of health care resources and gout-related
      drugs than the other groups. Overall, the doses of allopurinol or febuxostat
      remained unchanged over time.

PMID- 23861233
TI  - The demographic and contextual correlates of work-related repetitive strain
      injuries among Canadian men and women.
AB  - BACKGROUND: The study sought to identify gender differences in work-related
      repetitive strain injuries (RSI), as well as examine the degree to which non-work
      factors such as family roles interact with gender to modify RSI risk. Another aim
      is to examine whether there are potential provincial differences in work-related
      RSI risk. METHODS: The 2003/2005 Canadian Community Health Survey included over
      89,000 respondents who reported working in the past 12 months. Separate multi
      level models for men and women were used to identify the correlates of work
      related RSIs. RESULTS: Women reported sustaining more work-related RSIs than men.
      Also, having one or more children in the household was associated with lower work
      related RSI risk for females. Both men and women in British Columbia reported
      higher work-related RSI rates than in Ontario. CONCLUSIONS: Gender contributes to
      RSI risk in multiple and diverse ways based on labor market segregation, non-work
      exposures, and possibly biological vulnerability, which suggests more tailored
      interventions. Also, the provincial differences indicate that monitoring and
      surveillance of work injury across jurisdictions can assist in province-wide
      prevention and occupational health and safety evaluation.

PMID- 23861234
TI  - Bendamustine in chronic lymphocytic leukemia: outcome according to different
      clinical and biological prognostic factors in the everyday clinical practice.
AB  - Bendamustine proved to be effective for the treatment of chronic lymphocytic
      leukemia (CLL). However, the relationship between its activity with clinico
      biological prognosticators has been addressed only in few studies. We
      retrospectively evaluated the efficacy of bendamustine, in a real-life contest,
      on 142 patients, median age 70 years, median number of previous regimens 2 (0-8,
      13% previously untreated). Bendamustine was administered for a median number of 4
      cycles, in 84% of cases with rituximab. Overall (ORR) and complete response (CRR)
      rates were 68 and 16.5%, respectively. Multivariate analysis demonstrated a
      relationship between ORR and number of prior treatments (OR 0.25, 95% CI 0.08
      0.71; P = 0.009), del(17p) (OR 0.10, 95% CI 0.03-0.32; P < 0.001) and concomitant
      rituximab (OR 4.37, 95% CI 1.12-17.04; P = 0.033). The estimated 1- and 2-years
      overall survival (OS) and progression free survival (PFS) rates were 76, 61, 51,
      and 26%, respectively. Previous sensitivity to fludarabine (HR 0.36, 95% CI 0.16
      0.82), response to bendamustine (HR 0.21, 95% CI 0.10-0.45), and del(17p) (HR
      2.18, 95% CI 1.002-4.74) had a prognostic significance in multivariate analysis
      for PFS, while the number of previous therapies (HR 3.48, 95% CI 1.29-9.38; P =
      0.014), concomitant use of rituximab (HR 0.32, 95% CI 0.11-0.93) and response to
      bendamustine (HR 0.22, 95% CI 0.07-0.66) were significant for OS. Side effects
      included grade 3-4 neutropenia, infections, thrombocytopenia and anemia which
      occurred in 40, 14, 14, and 10% of patients, respectively. These results confirm
      the activity and safety of bendamustine and rituximab combination even in
      patients with unfavorable clinical and biological features excluding del(17p).

PMID- 23861235
TI  - Bio-inspired high-performance and recyclable cross-linked polymers.
AB  - Bio-inspired molecular design and synthesis of high-performance and recyclable
      cross-linked polymers is reported. Reversible cross-links between hard segments
      are incorporated into linear segmented polyurethane via Diels-Alder reaction
      between maleimide pendant group and furan cross-linker. The materials form
      hierarchical structure and exhibit excellent properties with high stiffness,
      strength and toughness, and can be easily thermally reshaped and re-mended. 

PMID- 23861236
TI  - Autoantibodies against zinc transporter 8 are related to age, metabolic state and
      HLA DR genotype in children with newly diagnosed type 1 diabetes.
AB  - BACKGROUND: We set out to define the characteristics of humoral autoimmunity
      against ZnT8 in children and adolescents with newly diagnosed T1D in relation to
      age and metabolic status at diagnosis, human leucocyte antigen (HLA) genotype and
      family history of T1D. METHODS: A total of 2115 subjects <15 years of age were
      analysed for antibodies against zinc transporter 8, ICA, GADA, IAA, IA-2A, HLA DR
      DQ genotype, blood pH, plasma glucose and beta-hydroxybutyrate concentrations.
      Their family history of T1D was also recorded. RESULTS: Zinc transporter 8
      antibodies (ZnT8A) were detected in 63% of the cases. ZnT8A positivity was
      associated with older age at diagnosis (mean 8.2 years versus 7.5 years, p <
      0.001). Seven subjects (0.3%) had ZnT8A as their single autoantibody. Diabetic
      ketoacidosis at diagnosis was less common among subjects with ZnT8A than among
      those without (16% versus 20%, p = 0.012). The prevalence of ZnT8A was decreased
      in DR3/DR4 heterozygotes when compared with those with other DR combinations (p <
      0.001). Subjects with the neutral DR13-DQB1*0604 haplotype tested more frequently
      positive for ZnT8A than the rest of the population (p < 0.001). A positive family
      history of T1D showed no association with ZnT8A prevalence or levels.
      CONCLUSIONS: Antibodies for ZnT8 is related to age and metabolic status at
      diagnosis as well as HLA genotype but does not significantly improve the
      detection rate of beta-cell autoimmunity in Finnish children and adolescents
      affected by T1D.

PMID- 23861237
TI  - Work-related injuries among union drywall carpenters in Washington State, 1989
      2008.
AB  - BACKGROUND: Drywall installers are at high-risk of work-related injury.
      Comprehensive descriptive epidemiology of injuries among drywall installers,
      particularly over time, is lacking. METHODS: We identified worker-hours and
      reported and accepted workers' compensation (WC) claims for a 20-year (1989-2008)
      cohort of 24,830 Washington State union carpenters. Stratified by predominant
      type of work (drywall installation, other carpentry), work-related injury rates
      were examined over calendar time and by worker characteristics. Expert interviews
      provided contextual details. RESULTS: Drywall installers' injury rates, higher
      than those of other carpenters, declined substantially over this period by 73.6%.
      Common injury mechanisms were struck by/against, overexertion and falls. Drywall
      material was considered a contributing factor in 19.7% of injuries. One-third of
      these drywall material-related injuries resulted in paid lost time, compared to
      19.4% of injuries from other sources. Rates of injury were particularly high
      among workers with 2 to <4 years in the union. Notable declines over time in
      rates of overexertion injury in which drywall material was a contributing factor
      were still observed after controlling for secular temporal trends. Experts
      highlighted changes over the past 20 years that improved both work safety and, in
      some cases, production. CONCLUSIONS: Declines in drywall installers' injury rates
      over time likely reflect, in part, enhanced workplace safety, including efforts
      to reduce overexertion hazards associated with handling drywall. Continued injury
      prevention efforts are needed, particularly for less tenured workers. Given the
      potential for under-reporting to WC, additional sources of health outcomes data
      may provide a more complete picture of workers' health.

PMID- 23861238
TI  - In-situ formation and assembly of gold nanoparticles by gum arabic as efficient
      photothermal agent for killing cancer cells.
AB  - Gold nanoparticles (AuNPs) have been established to sufficiently eradicate tumors
      by means of heat production for photothermal therapy. However, the translation of
      the AuNPs from bench to the clinic still remains to be solved until realizing
      high bioclearance after treatment. Herein, we developed a simple strategy for
      simultaneous formation and assembly of small-size gold nanoparticles (Au-SNPs) to
      form a novel nanocomposite in the presence of gum arabic (GA) by synchrotron X
      ray irradiation in an aqueous solution within 5 min. GA, a porous polysaccharide,
      can not only provide a confined space in which to produce uniform Au-SNPs (1.6 +/
      0.7 nm in diameter), but can also facilitate the formation of Au-SNPs@GA
      (diameter ~ 40 nm) after irradiating synchrotron X-rays. Specifically, the Au
      SNPs@GA possesses high thermal stability and a strong photothermal effect for
      killing cancer cells. Importantly, a bioclearance study demonstrated that the Au
      SNPs@GA can be gradually excreted by the renal and hepatobiliary system, which
      might be due to the breakdown and oxidation of GA under irradiating synchrotron X
      rays. Thus, the novel gold nanocomposite can be promising photothermal agents for
      cancer treatment at the therapeutic level, minimizing toxicity concerns regarding
      long-term accumulation in vivo. 

PMID- 23861239
TI  - Association of HPV types 6, 11, 16, and 18 DNA detection and serological response
      in unvaccinated adolescent women.
AB  - Antibodies directed against the human papillomavirus (HPV) L1 protein are
      detected in approximately 70% of individuals with HPV infections. The factors
      associated with a serological response are not characterized. It is hypothesized
      that the HPV viral load, duration of detection, or both would be associated with
      seropositivity in adolescent women. Adolescent women (n = 117), ages 15-17 at
      enrolment were followed for a mean of 6.2 years. Quarterly vaginal swabs (mean 22
      per participant) were used to identify HPV 6, 11, 16, or 18 DNA (Roche PCR/Linear
      Array). Type-specific HPV infection was defined as >=2 positive assays. To
      approximate viral load, Roche PCR/Linear Array test strips were scored visually
      based on the strength of signal relative to beta-globin controls. Sera collected
      near the end of study were tested by cLIA. Regression models were fit to assess
      associations between strength of signal (as represented by mean and cumulative
      strength of signal), duration of HPV detection, seropositivity, and serotiter.
      Detection of HPV DNA was associated with seropositivity for four types combined
      and for types 6, 16, and 18. Overall, 70.1% of DNA positive episodes were
      associated with type-specific seropositivity. The cumulative HPV DNA signal
      strength during periods of HPV detection for types 6, 11, 16, and 18 combined was
      associated with seropositivity (OR = 1.21, 95% CI 1.02-1.44 P = 0.026). No other
      HPV DNA predictors were found to be associated with seropositivity or serotiter.

PMID- 23861240
TI  - Physician response to pay-for-performance: evidence from a natural experiment.
AB  - This study exploits a natural experiment in the province of Ontario, Canada, to
      identify the impact of pay-for-performance (P4P) incentives on the provision of
      targeted primary care services and whether physicians' responses differ by age,
      size of patient population, and baseline compliance level. We use administrative
      data that cover the full population of Ontario and nearly all the services
      provided by primary care physicians. We employ a difference-in-differences
      approach that controls for selection on observables and selection on
      unobservables that may cause estimation bias. We implement a set of robustness
      checks to control for confounding from other contemporaneous interventions of the
      primary care reform in Ontario. The results indicate that responses were modest
      and that physicians responded to the financial incentives for some services but
      not others. The results provide a cautionary message regarding the effectiveness
      of employing P4P to increase the quality of health care.

PMID- 23861241
TI  - Improvement in health and possible reduction in disease activity using endurance
      exercise in patients with established polymyositis and dermatomyositis: a
      multicenter randomized controlled trial with a 1-year open extension followup.
AB  - OBJECTIVE: To determine the effects of a 12-week endurance exercise program on
      health, disability, VO2 max, and disease activity in a multicenter randomized
      controlled trial in patients with established polymyositis (PM) and
      dermatomyositis (DM), and to evaluate health and disability in a 1-year open
      extension study. METHODS: Patients were randomized into a 12-week endurance
      exercise program group (EG; n = 11) or a control group (CG; n = 10). Assessments
      of health (Short Form 36 [SF-36]), muscle performance (5 voluntary repetition
      maximum [5 VRM]), activities of daily living (ADL), patient preference (McMaster
      Toronto Arthritis Patient Preference Disability Questionnaire), VO2 max, and
      disease activity (International Myositis Assessment and Clinical Studies criteria
      of improvement of the 6-item core set) were performed at 0 and 12 weeks.
      Disability assessments were performed again at 52 weeks in an open extension
      period. All assessments were performed by blinded observers. RESULTS: The EG
      improved compared to the CG in SF-36 physical function and vitality (P = 0.010
      and P = 0.046, respectively), ADL score (P = 0.035), 5 VRM (P = 0.026), and VO2
      max (P = 0.010). More patients in the EG (7 of 11) were responders with reduced
      disease activity compared to none in the CG (P = 0.002). Correlations between VO2
      max and SF-36 physical function were 0.90 and 0.91 at 0 and 12 weeks,
      respectively (P < 0.05). The EG improvement in 5 VRM was sustained up to 52 weeks
      compared to baseline (5.7 kg; P < 0.001), but not in ADL score or SF-36.
      CONCLUSIONS: Endurance exercise improves health and may reduce disease activity
      in patients with established PM/DM. This potentially could be mediated through
      improved aerobic fitness. The results also indicate sustained muscle strength up
      to 1 year after a supervised program.

PMID- 23861243
TI  - Catalysis with Gold Complexes Immobilised on Carbon Nanotubes by pi-pi Stacking
      Interactions: Heterogeneous Catalysis versus the Boomerang Effect.
AB  - A new pyrene-tagged gold(I) complex has been synthesised and tested as a
      homogeneous catalyst. First, a simple 1,6-enyne was chosen as a model substrate
      for cyclisation by using different solvents to optimise the reaction conditions.
      The non-covalent immobilisation of our pyrene-tagged gold complex onto multi
      walled carbon nanotubes through pi-pi stacking interactions was then explored to
      obtain a supported homogeneous catalyst. The heterogenised catalyst and its
      homogeneous counterpart exhibited similar activity in a range of enyne
      cyclisation reactions. Bearing in mind that pi-pi interactions are affected by
      temperature and solvent polarity, the reuse and robustness of the supported
      homogeneous catalyst was tested to explore the scope and limitations of the
      recyclability of this catalyst. Under the optimised conditions, recyclability was
      observed by using the concept of the boomerang effect. 

PMID- 23861244
TI  - Do we need research ethics committees?

PMID- 23861245
TI  - Thinking harder about nudges.

PMID- 23861242
TI  - Pain and other non-neurological adverse events in children with sickle cell
      anemia and previous stroke who received hydroxyurea and phlebotomy or chronic
      transfusions and chelation: results from the SWiTCH clinical trial.
AB  - To compare the non-neurological events in children with sickle cell anemia (SCA)
      and previous stroke enrolled in SWiTCH. The NHLBI-sponsored Phase III multicenter
      randomized clinical trial stroke with transfusions changing to hydroxyurea
      (SWiTCH) (ClinicalTrials.gov NCT00122980) compared continuation of chronic blood
      transfusion/iron chelation to switching to hydroxyurea/phlebotomy for secondary
      stroke prevention and management of iron overload. All randomized children were
      included in the analysis (intention to treat). The Fisher's Exact test was used
      to compare the frequency of subjects who experienced at least one SCA-related
      adverse event (AE) or serious adverse event (SAE) in each arm and to compare
      event rates. One hundred and thirty three subjects, mean age 13 +/- 3.9 years
      (range 5.2-19.0 years) and mean time of 7 years on chronic transfusion at study
      entry, were randomized and treated. Numbers of subjects experiencing non
      neurological AEs were similar in the two treatment arms, including SCA-related
      events, SCA pain events, and low rates of acute chest syndrome and infection.
      However, fewer children continuing transfusion/chelation experienced SAEs (P =
      0.012), SCA-related SAEs (P = 0.003), and SCA pain SAEs (P = 0.016) as compared
      to children on the hydroxyurea/phlebotomy arm. The timing of phlebotomy did not
      influence SAEs. Older age at baseline predicted having at least 1 SCA pain event.
      Patients with recurrent neurological events during SWiTCH were not more likely to
      experience pain. In children with SCA and prior stroke, monthly transfusions and
      daily iron chelation provided superior protection against acute vaso-occlusive
      pain SAEs when compared to hydroxyurea and monthly phlebotomy.

PMID- 23861246
TI  - Mer receptor tyrosine kinase is a therapeutic target in pre-B-cell acute
      lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is currently treated with an intense regimen
      of chemotherapy yielding cure rates near 85%. However, alterations to treatment
      strategies using available drugs are unlikely to provide significant improvement
      in survival or decrease therapy-associated toxicities. Here, we report ectopic
      expression of the Mer receptor tyrosine kinase in pre-B-cell ALL (B-ALL) cell
      lines and pediatric patient samples. Inhibition of Mer in B-ALL cell lines
      decreased activation of AKT and MAPKs and led to transcriptional changes,
      including decreased expression of antiapoptotic PRKCB gene and increase in
      proapoptotic BAX and BBC3 genes. Further, Mer inhibition promoted
      chemosensitization, decreased colony-forming potential in clonogenic assays, and
      delayed disease onset in a mouse xenograft model of leukemia. Our results
      identify Mer as a potential therapeutic target in B-ALL and suggest that
      inhibitors of Mer may potentiate lymphoblast killing when used in combination
      with chemotherapy. This strategy could reduce minimal residual disease and/or
      allow for chemotherapy dose reduction, thereby leading to improved event-free
      survival and reduced therapy-associated toxicity for patients with B-ALL.
      Additionally, Mer is aberrantly expressed in numerous other malignancies
      suggesting that this approach may have broad applications. 

PMID- 23861247
TI  - Expression profiling of TCR-engineered T cells demonstrates overexpression of
      multiple inhibitory receptors in persisting lymphocytes.
AB  - Despite significant progress in the development of adoptive cell-transfer
      therapies (ACTs) using gene-engineered T cells, little is known about the fate of
      cells following infusion. To address that, we performed a comparative analysis of
      gene expression between T-cell receptor-engineered lymphocytes persisting in the
      circulation 1 month after administration and the product that was infused. We
      observed that 156 genes related to immune function were differentially expressed,
      including underexpression of stimulators of lymphocyte function and
      overexpression of inhibitory genes in postinfusion cells. Of genes overexpressed
      postinfusion, the product of programmed cell death 1 (PDCD1), coinhibitory
      receptor PD-1, was expressed at a higher percentage in postinfusion lymphocytes
      than in the infusion product. This was associated with a higher sensitivity to
      inhibition of cytokine production by interaction with its ligand PD-L1.
      Coinhibitory receptor CD160 was also overexpressed in persisting cells, and its
      expression was associated with decreased reactivity, which surprisingly was found
      to be ligand-independent. These results contribute to a deeper understanding of
      the properties of transgenic lymphocytes used to treat human malignancies and may
      provide a rationale for the development of combination therapies as a method to
      improve ACT.

PMID- 23861248
TI  - Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after
      allogeneic peripheral blood stem cell transplantation: results of a phase 2
      trial.
AB  - B cells are implicated in the pathophysiology of chronic graft-vs-host disease
      (GVHD), and phase 2 trials suggest that B cell depletion can treat established
      chronic GVHD. We hypothesized that posttransplantation B cell depletion could
      prevent the occurrence of chronic GVHD. We performed a 65-patient phase 2 trial
      of rituximab (375 mg/m(2) IV), administered at 3, 6, 9, and 12 months after
      transplantation. Rituximab administration was safe without severe infusional
      adverse events. The cumulative incidences of chronic GVHD and systemic
      corticosteroid-requiring chronic GVHD at 2 years from transplantation were 48%
      and 31%, respectively, both lower than the corresponding rates in a concurrent
      control cohort (60%, P = .1, and 48.5%, P = .015). There was no difference in
      relapse incidence, but treatment-related mortality at 4 years from
      transplantation was significantly lower in treated subjects when compared with
      controls (5% vs 19%, P = .02), and overall survival was superior at 4 years (71%
      vs 56%, P = .05). At 2 years from transplantation, the B-cell activating factor/B
      cell ratio was significantly higher in subjects who developed chronic GVHD in
      comparison with those without chronic GVHD (P = .039). Rituximab can prevent
      systemic corticosteroid-requiring chronic GVHD after peripheral blood stem cell
      transplantation and should be tested in a prospective randomized trial.

PMID- 23861249
TI  - An evolutionarily conserved program of B-cell development and activation in
      zebrafish.
AB  - Teleost fish are among the most ancient vertebrates possessing an adaptive immune
      system with B and T lymphocytes that produce memory responses to pathogens. Most
      bony fish, however, have only 2 types of B lymphocytes, in contrast to the 4
      types available to mammals. To better understand the evolution of adaptive
      immunity, we generated transgenic zebrafish in which the major immunoglobulin M
      (IgM(+)) B-cell subset expresses green fluorescence protein (GFP) (IgM1:eGFP). We
      discovered that the earliest IgM(+) B cells appear between the dorsal aorta and
      posterior cardinal vein and also in the kidney around 20 days postfertilization.
      We also examined B-cell ontogeny in adult IgM1:eGFP;rag2:DsRed animals, where we
      defined pro-B, pre-B, and immature/mature B cells in the adult kidney. Sites of B
      cell development that shift between the embryo and adult have previously been
      described in birds and mammals. Our results suggest that this developmental shift
      occurs in all jawed vertebrates. Finally, we used IgM1:eGFP and
      cd45DsRed;blimp1:eGFP zebrafish to characterize plasma B cells and investigate B
      cell function. The IgM1:eGFP reporter fish are the first nonmammalian B-cell
      reporter animals to be described. They will be important for further
      investigation of immune cell evolution and development and host-pathogen
      interactions in zebrafish. 

PMID- 23861250
TI  - Defective tubulin organization and proplatelet formation in murine megakaryocytes
      lacking Rac1 and Cdc42.
AB  - Blood platelets are anuclear cell fragments that are essential for blood
      clotting. Platelets are produced by bone marrow megakaryocytes (MKs), which
      extend protrusions, or so-called proplatelets, into bone marrow sinusoids.
      Proplatelet formation requires a profound reorganization of the MK actin and
      tubulin cytoskeleton. Rho GTPases, such as RhoA, Rac1, and Cdc42, are important
      regulators of cytoskeletal rearrangements in platelets; however, the specific
      roles of these proteins during platelet production have not been established.
      Using conditional knockout mice, we show here that Rac1 and Cdc42 possess
      redundant functions in platelet production and function. In contrast to a single
      deficiency of either protein, a double-deficiency of Rac1 and Cdc42 in MKs
      resulted in macrothrombocytopenia, abnormal platelet morphology, and impaired
      platelet function. Double-deficient bone marrow MKs matured normally in vivo but
      displayed highly abnormal morphology and uncontrolled fragmentation.
      Consistently, a lack of Rac1/Cdc42 virtually abrogated proplatelet formation in
      vitro. Strikingly, this phenotype was associated with severely defective tubulin
      organization, whereas actin assembly and structure were barely affected.
      Together, these results suggest that the combined action of Rac1 and Cdc42 is
      crucial for platelet production, particularly by regulating microtubule dynamics.

PMID- 23861252
TI  - Relationships between organizational workplace characteristics and perceived
      workplace strain in call-centers in France.
AB  - BACKGROUND: Our objective was to study the associations between organizational
      workplace characteristics (OC) reported by call-center (CC) managers and
      workplace stressors reported by call-handlers. METHODS: The managers of 107 CCs
      were interviewed by their occupational physicians using a questionnaire designed
      to specifically explore OC in the CCs. Four thousand two call-handlers from these
      CCs completed a self-report questionnaire including the Karasek and Siegrist work
      stressor questionnaires and two specific items on other workplace stressors.
      RESULTS: Around one-third of the OC examined were associated with the
      demand/control ratio, the perception of demanding work and ethical conflicts,
      however, far fewer OC were associated with the effort/reward ratio. Most OC were
      associated with higher levels of job stressors. Some had strong, systematic
      negative associations with stressors (e.g., highly formatted instructions for the
      client relationship). CONCLUSIONS: These findings could help in targeting job
      stressor prevention and health improvement strategies in CCs.

PMID- 23861253
TI  - When do fat taxes increase consumer welfare? Reply to Neill.

PMID- 23861251
TI  - Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice.
AB  - Gray platelet syndrome (GPS) is an inherited bleeding disorder associated with
      macrothrombocytopenia and alpha-granule-deficient platelets. GPS has been linked
      to loss of function mutations in NEABL2 (neurobeachin-like 2), and we describe
      here a murine GPS model, the Nbeal2(-/-) mouse. As in GPS, Nbeal2(-/-) mice
      exhibit splenomegaly, macrothrombocytopenia, and a deficiency of platelet alpha
      granules and their cargo, including von Willebrand factor (VWF), thrombospondin
      1, and platelet factor 4. The platelet alpha-granule membrane protein P-selectin
      is expressed at 48% of wild-type levels and externalized upon platelet
      activation. The presence of P-selectin and normal levels of VPS33B and VPS16B in
      Nbeal2(-/-) platelets suggests that NBEAL2 acts independently of VPS33B/VPS16B at
      a later stage of alpha-granule biogenesis. Impaired Nbeal2(-/-) platelet function
      was shown by flow cytometry, platelet aggregometry, bleeding assays, and
      intravital imaging of laser-induced arterial thrombus formation. Microscopic
      analysis detected marked abnormalities in Nbeal2(-/-) bone marrow megakaryocytes,
      which when cultured showed delayed maturation, decreased survival, decreased
      ploidy, and developmental abnormalities, including abnormal extracellular
      distribution of VWF. Our results confirm that alpha-granule secretion plays a
      significant role in platelet function, and they also indicate that abnormal alpha
      granule formation in Nbeal2(-/-) mice has deleterious effects on megakaryocyte
      survival, development, and platelet production. 

PMID- 23861254
TI  - A base-stabilized sila-beta-lactone and a donor/acceptor-stabilized silanoic
      acid.

PMID- 23861255
TI  - Integrative effect of defective interfering RNA accumulation and helper virus
      attenuation is responsible for the persistent infection of Japanese encephalitis
      virus in BHK-21 cells.
AB  - Persistence of RNA viruses is often, but not always, associated with the
      production of defective interfering (DI) particles. To investigate possible roles
      of DI particles and helper viruses in RNA virus persistence, persistent infection
      with Japanese encephalitis virus (JEV) was established in baby hamster kidney
      (BHK-21) cells. At the 6th and 7th serial undiluted passages of JEV on BHK-21
      cells, viral persistence was established spontaneously with DI RNA generation.
      Seven cell clones exhibiting persistent infection were obtained from the initial
      BHK-21 cell batches exhibiting JEV persistence, and maintained for over 400 days.
      Most cell clones produced infectious particles (10(1) -10(5)  PFU/ml)
      continuously, expressed viral proteins, and resisted homologous superinfection.
      Two helper viruses, chvBS6-3 and chvBS7-1, were isolated from two of the seven
      cell clones, and characterized to investigate their roles in JEV persistence.
      While chvBS6-3 was restored to its full cytopathicity in the absence of DI RNA,
      chvBS7-1 exhibited almost no cytopathicity, regardless of DI RNA co-replication.
      Attenuation of chvBS7-1 did not appear to be due to inadequate adsorption or
      genome replication, but due to inefficient egress of the assembled progeny
      virions, suggesting altered helper virus emergence during JEV persistence in BHK
      21 cells. These observations suggest that at least two mechanisms are involved in
      JEV persistence; a DI RNA-dependent mechanism, where DI RNA co-replication
      nullifies the helper virus's cytopathicity, or a DI RNA-independent mechanism,
      where the helper virus is self-attenuated. This study provides a useful in vitro
      tool for understanding the mechanisms underlying RNA virus persistent infections.

PMID- 23861256
TI  - Enhanced adhesion of preosteoblasts inside 3D PCL scaffolds by polydopamine
      coating and mineralization.
AB  - In tissue engineering, fabrication of 3D scaffolds with well-defined, inter
      connected pores followed by culture of mammalian cells is a typical approach. In
      practice, however, hydrophobicity of scaffold surfaces is not suitable for cells
      to be adhered because of poor wettability. Especially, infiltration followed by
      adhesion of cells inside hydrophobic scaffolds remains as a challenge. Thus,
      hydrophilic conversions of the surfaces regardless of surface location are
      critical for success. Herein, a method to enhance infiltration and adhesion of
      preosteoblasts inside hydrophobic poly(epsilon-caprolactone) (PCL) scaffolds by a
      bio-inspired, hydroxyapatite formation is demonstrated. The approach can be a
      general method for controlling hydrophilicity of inner surfaces of scaffolds. 

PMID- 23861257
TI  - Silicon-based material with spiro-annulated fluorene/triphenylamine as host and
      exciton-blocking layer for blue electrophosphorescent devices.
AB  - A novel silicon-based compound, 10-phenyl-2'-(triphenylsilyl)-10H-spiro[acridine
      9,9'-fluorene] (SSTF), with spiro structure has been designed, synthesized, and
      characterized. Its thermal, electronic absorption, and photoluminescence
      properties were studied. Its energy levels make it suitable as a host material or
      exciton-blocking material in blue phosphorescent organic light-emitting diodes
      (PhOLEDs). Accordingly, blue-emitting devices with iridium(III) bis[(4,6
      difluorophenyl)-pyridinato-N,C(2)']picolinate (FIrpic) as phosphorescent dopant
      have been fabricated and show high efficiency with low roll-off. In particular,
      44.0 cd A(-1) (41.3 lm W(-1)) at 100 cd m(-2) and 41.9 cd A(-1) (32.9 lm W(-1))
      at 1000 cd m(-2) were achieved when SSTF was used as host material; 28.1 lm W(-1)
      at 100 cd m(-2) and 20.6 lm W(-1) at 1000 cd m(-2) were achieved when SSTF was
      used as exciton-blocking layer. All of the results are superior to those of the
      reference devices and show the potential applicability and versatility of SSTF in
      blue PhOLEDs.

PMID- 23861258
TI  - What is a promonocyte?

PMID- 23861259
TI  - Illness perceptions and fatigue in systemic vasculitis.
AB  - OBJECTIVE: To compare illness perceptions among patients with different forms of
      vasculitis, identify risk factors for negative illness perceptions, and determine
      the association between illness perceptions and fatigue. METHODS: Participants
      were recruited from an online vasculitis registry to complete the revised Illness
      Perception Questionnaire (IPQ-R). The mean scores on each IPQ-R dimension were
      compared across different types of vasculitis. Cluster analysis and stepwise
      regression identified predictors of negative illness perception. Fatigue was
      measured using the general subscale of the Multidimensional Fatigue Inventory
      (MFI-20). Patient-reported measures of disease activity and IPQ-R dimensions were
      assessed in relation to MFI-20 scores using linear regression in sequential,
      additive models with model-fit comparisons. RESULTS: In total, 692 participants
      with 9 types of vasculitis completed the IPQ-R. For 6 of the 8 IPQ-R dimensions,
      there were no significant differences in mean scores between the different
      vasculitides. Scores in the identity and cyclical dimensions were significantly
      higher in Behcet's disease compared with other types of vasculitis (13.5 versus
      10.7 for identity and 4.0 versus 3.2 for cyclical [P < 0.05]). Younger age (odds
      ratio [OR] 1.04, 95% confidence interval [95% CI]1.02-1.06), depression (OR 4.94,
      95% CI 2.90-8.41), active disease status (OR 2.05, 95% CI 1.27-3.29), and poor
      overall health (OR 3.92, 95% CI 0.88-17.56) were associated with negative illness
      perceptions. The sequential models demonstrated that the IPQ-R dimensions
      explained an equivalent proportion of variability in fatigue scores compared with
      measures of disease activity. CONCLUSION: Illness perceptions are similar across
      different types of vasculitis, and younger age is a risk factor for negative
      illness perceptions. Illness perceptions explain differences in fatigue scores
      beyond what can be explained by measures of disease activity.

PMID- 23861260
TI  - Reirradiation of canine nasal carcinomas treated with coarsely fractionated
      radiation protocols: 37 cases.
AB  - Data from 37 dogs with nasal carcinomas treated with two or more coarsely
      fractionated courses of radiation therapy (RT) were retrospectively reviewed. The
      median radiation dose for the first course of RT was 24 Gray (Gy). All dogs
      clinically responded, and 11 had complete resolution of signs for a median of 114
      days. Dogs were retreated at relapse, with a median dose of 20 Gy, and 26 of 37
      dogs (70%) had clinical responses. The second course of RT was initiated at a
      median of 150 days following completion of the first course. Side effects were
      mild: four dogs had chronic ocular conditions necessitating medication, one of
      which required enucleation. Median survival time (ST) from the first dose of RT
      was 453 days and 180 days from the first dose of the second course of RT. The
      following factors were examined but were not significant for survival: total RT
      dose, dose of the first course of RT, complete resolution of clinical signs, use
      of either chemotherapy or nonsteroidal anti-inflammatory drugs (NSAIDs), and
      stage (T1/T2 versus T3/T4). Dogs responded well to reirradiation with a subset
      experiencing chronic ocular side effects. 

PMID- 23861261
TI  - Liver failure in a dog following suspected ingestion of blue-green algae
      (Microcystis spp.): a case report and review of the toxin.
AB  - A 2.5 yr old spayed female Weimaraner presented after ingestion of blue-green
      algae (Microcystis spp.). One day prior to presentation, the patient was swimming
      at a local lake known to be contaminated with high levels of blue-green algae
      that was responsible for deaths of several other dogs the same summer. The
      patient presented 24 hr after exposure with vomiting, inappetence, weakness, and
      lethargy. Blood work at the time of admission was consistent with acute hepatic
      failure, characteristic findings of intoxication by Microcystis spp. Diagnosis
      was suspected by analyzing a water sample from the location where the patient was
      swimming. Supportive care including fluids, fresh frozen plasma, whole blood,
      vitamin K, B complex vitamins, S-adenosyl methionine, and Silybum marianum were
      started. The patient was discharged on supportive medications, and follow-up
      blood work showed continued improvement. Ingestion is typically fatal for most
      patients. This is the first canine to be reported in the literature to survive
      treatment after known exposure. 

PMID- 23861262
TI  - Brainstem oligodendroglioma in a puppy.
AB  - A 5 mo old male golden retriever presented for evaluation of an acute onset,
      progressive neurologic disease. Although computed tomography (CT) was
      unremarkable, MRI identified an ill-defined mass located in the medulla, which
      was considered likely responsible for the clinical signs. The imaging features
      closely resembled the classic features of human brainstem gliomas in the
      pediatric population. Histopathologic examination confirmed the lesion to be an
      anaplastic oligodendroglioma. 

PMID- 23861263
TI  - Comparison of gravity collection versus suction collection for transfusion
      purposes in dogs.
AB  - Blood donation is an essential step in transfusion medicine that must take into
      account the donor's welfare, collection effectiveness, and blood product quality.
      This prospective study enrolled 13 canine blood donors, each subjected to both
      gravity and suction collection methods, in a randomized order. Clinical
      parameters, including heart rate (HR), respiratory rate (RR), systolic blood
      pressure (SBP), and rectal temperature (RT), were evaluated at four time points,
      including when the donor was on the floor and on the collection table, and before
      and after blood donation. The number of times the donor and needle required
      repositioning, the duration of the donation, the noise created by the apparatus,
      and the presence of a hematoma were evaluated. The weight, index of hemolysis,
      and hematocrit of each unit of blood were recorded. There was no significant
      difference between collection methods for either the clinical parameters at each
      time point or the prevalence of hematoma formation, the frequency of needle
      repositioning, the hemolysis index, or hematocrit. Collection by suction was
      noisier (P < 0.0001), faster (P = 0.004), and associated with significantly less
      donor repositioning (P = 0.007). Suction appears to be a safe and cost-effective
      method that should be considered to optimize blood donation. 

PMID- 23861264
TI  - Use of MRI for the early diagnosis of masticatory muscle myositis.
AB  - The medical records of two dogs that were diagnosed with masticatory muscle
      myositis (MMM) were reviewed. The reported clinical signs included intense pain
      when opening the mouth and restricted jaw movement. MRI detected widespread,
      symmetrical, and inhomogeneously hyperintense areas in the masticatory muscle.
      Electromyography (EMG) demonstrated severe and spontaneous pathologic activity in
      the temporal and masseter muscles. With early therapeutic treatment, remission of
      symptoms occurred within 2 mo, and no relapses were observed for the subsequent 2
      yr. The gold standard for the diagnosis of MMM is the 2M antibody test, but the
      purpose of this study was to evaluate the use of MRI as an accurate and efficient
      diagnostic tool for the initiation of early therapy for the treatment of muscle
      myositis. 

PMID- 23861265
TI  - Evaluation of a gelatin matrix as a topical hemostatic agent for hepatic bleeding
      in the dog.
AB  - New generation topical hemostatic agents containing thrombin have been developed
      for use in surgical procedures when control of bleeding by conventional methods
      is either ineffective or impractical. The authors compared the safety, hemostatic
      efficacy, and handling characteristics of a thrombin-containing topical surgical
      hemostatic agent (a gelatin matrix) to a hemostatic gelatin sponge for treatment
      of parenchymal bleeding after liver biopsy. Fourteen dogs were enrolled in this
      prospective clinical study. Paired 1.5 cm * 1.5 cm and 0.5 cm deep liver biopsies
      were obtained via laparotomy for each dog. One bleeding liver biopsy lesion was
      treated with the gelatin matrix and the other with a gelatin sponge. The treated
      liver biopsy sites were compared for bleeding severity, time to hemostasis,
      cumulative blood loss, and hemostatic agent handling characteristics. Median time
      to hemostasis was significantly shorter (P = 0.034) and median cumulative blood
      loss was significantly lower (P = 0.033) for the lesions treated with the gelatin
      matrix than the gelatin sponge. Adverse reactions were not observed within the
      first 24 hr postoperatively. When used to control parenchymal bleeding from liver
      biopsy sites in the dog, the evaluated gelatin matrix was safe and more effective
      than the gelatin sponge. 

PMID- 23861266
TI  - Hypercalcemia of malignancy associated with renal cell carcinoma in a dog.
AB  - A 10 yr old castrated male Siberian husky was evaluated for polyuria, polydipsia,
      a retroperitoneal mass, and urolithiasis. A marked elevation in Ca was noted on
      initial blood work, and results of additional testing were consistent with
      hypercalcemia of malignancy, including an elevated parathyroid hormone-related
      peptide (PTHrp) value. Based on clinical signs, blood work, diagnostic imaging,
      and cytology results, unilateral renal neoplasia was suspected. Following a
      complete right nephrectomy and cystotomy, histopathologic examination confirmed a
      diagnosis of renal cell carcinoma (RCC). Five days postoperatively, the
      hypercalcemia had nearly resolved and the PTHrp was zero. This is the first
      reported case of hypercalcemia of malignancy associated with RCC in a dog. 

PMID- 23861267
TI  - Zygomatic salivary gland diseases in the dog: three cases diagnosed by MRI.
AB  - This article describes three original cases of zygomatic gland disease in the dog
      diagnosed by low-field MRI and treated by a modified lateral orbitotomy with
      zygomatic osteotomy. Presenting complaints included exophthalmia, protrusion of
      the third eyelid, and periorbital swelling without any history of trauma. Low
      field MRI allowed for adequate diagnosis of zygomatic gland disease in all cases
      and provided detailed information about both the specific tissue characteristics
      of each lesion and extension into surrounding structures. MRI findings were also
      helpful for surgical planning and dictated the choice of a modified lateral
      orbitotomy without removal of the orbital ligament. Histopathologic diagnosis for
      each of the three dogs was a mucocele, a malignant mixed salivary tumor, and
      sialadenitis. 

PMID- 23861268
TI  - Effects of ampicillin/sulbactam and enrofloxacin on the blood pressure of
      isoflurane anesthetized dogs.
AB  - A blinded, prospective, randomized crossover study was performed to determine the
      effects of ampicillin Na/sulbactam Na and enrofloxacin on the blood pressure (BP)
      of healthy anesthetized dogs. Eight dogs were anesthetized three different times.
      They randomly received enrofloxacin, ampicillin Na/sulbactam Na, and saline.
      Systolic, diastolic, and mean arterial BPs (SAP, DAP, and MAP, respectively),
      heart rate (HR), O2 saturation of hemoglobin, end-tidal CO2 (ETCO2)
      concentration, inspired isoflurane concentration, end-tidal isoflurane (ETiso)
      concentration, respiratory rate, electrocardiogram, and body temperature were
      measured for 20 min prior to administration of treatment, during administration
      over 30 min, and for 30 min after administration. There was no significant
      difference in the SAP or ETiso. There was no significant change in the arterial
      pressure values over time in the enrofloxacin and ampicillin Na/sulbactam Na
      groups. The control group's MAP increased over time and was increased compared
      with the enrofloxacin group at times 25, 35, 45, and 55. The statistical
      difference between the enrofloxacin and the control groups was due to an increase
      in the MAP in the control group, not a decrease in the enrofloxacin group's BP.
      Neither enrofloxacin nor ampicillin Na/sulbactam Na caused hypotension in healthy
      dogs anesthetized with isoflurane and fentanyl. 

PMID- 23861269
TI  - Supernumerary kidney with ipsilateral cryptorchidism in a cat.
AB  - An 8 wk old male domestic longhair was presented with an abdominal mass and
      cryptorchidism. A 2 cm mass was palpable in the midabdomen. Ultrasonography
      confirmed a complex, septated, cystic mass adjacent and caudal to the right
      kidney. A normally appearing left kidney was present. Pathologic examination of
      the excised abdominal mass revealed it to be a kidney with an attached, normal
      caliber ureter. At surgery, this kidney was separate from the parenchyma of the
      second, cranial, right kidney. Subsequently, the second right kidney became
      hydronephrotic and was removed together with the cryptorchid testis and an
      apparently hypoplastic ureter. This is the first report of a supernumerary kidney
      in a cat, adding it to the differential diagnoses of abdominal masses. 

PMID- 23861270
TI  - Assurance calculations for planning clinical trials with time-to-event outcomes.
AB  - We consider the use of the assurance method in clinical trial planning. In the
      assurance method, which is an alternative to a power calculation, we calculate
      the probability of a clinical trial resulting in a successful outcome, via
      eliciting a prior probability distribution about the relevant treatment effect.
      This is typically a hybrid Bayesian-frequentist procedure, in that it is usually
      assumed that the trial data will be analysed using a frequentist hypothesis test,
      so that the prior distribution is only used to calculate the probability of
      observing the desired outcome in the frequentist test. We argue that assessing
      the probability of a successful clinical trial is a useful part of the trial
      planning process. We develop assurance methods to accommodate survival outcome
      measures, assuming both parametric and nonparametric models. We also develop
      prior elicitation procedures for each survival model so that the assurance
      calculations can be performed more easily and reliably. We have made free
      software available for implementing our methods.

PMID- 23861273
TI  - Spine and scapular pain: an unusual presentation of colon adenocarcinoma.
AB  - We are presenting an elderly Caucasian woman who was admitted to our hospital for
      severe lower back pain and scapular pain for 8 days. She had a history of spinal
      stenosis and we believed this was the aetiology of her pain. However, her pain
      was not subsiding and hence an MRI spine was performed. It revealed spinal
      stenosis and abnormal signal in the lower thoracic and lumbar vertebrae. Hence a
      bone biopsy was performed that came back as metastatic adenocarcinoma. She
      underwent a bone scan and revealed diffuse disease in thoracic, lumbar, sacral
      spine as well as third and 10th ribs. Her CT chest/abdomen/pelvis revealed no
      primary tumour. A mass was detected on her colonscopy, and pathology revealed
      adenocarcinoma. She underwent palliative radiation and one cycle of chemotherapy.
      She was discharged to home hospice care. It is very rare to have osseous
      metastases as the only manifestation of colon cancer. 

PMID- 23861274
TI  - Fountain of steroid from an ectopic ACTH-producing tumour.
AB  - This case is of a 39-year-old Filipino woman who within 2 months developed,
      Cushing's features she had no known comorbidities and no history of steroid
      intake. The patient also presented with hyperpigmentation of knuckles and toes,
      metabolic alkalosis and persistent hypokalaemia noted as proximal muscle
      weakness. The patient was referred to our institution for acutely worsening
      behavioural and psychiatric changes. Work-up for endogenous Cushing's syndrome
      revealed a significant adrenocorticotropic hormone production from an ectopic
      source. Further imaging was requested to locate the tumour, but the patient
      eventually succumbed to the drastic complications of hypercortisolism. On
      autopsy, the patient was found to have an ectopic well-differentiated
      neuroendocrine tumour located at the pancreatic head with metastasis to the right
      hepatic lobe. 

PMID- 23861275
TI  - Aspiration of a speaking valve.
AB  - Foreign body aspiration (FBA) is a relatively common and serious condition that
      can result in a spectrum of presentations ranging from incidental to acutely life
      threatening. Described here is a case of aspiration of a tracheo-oesophageal
      speaking valve through a permanent tracheostomy that went unnoticed for a number
      of years, and an overview of the technique used for its removal. A 70-year-old ex
      heavy smoker with a permanent tracheo-oesophageal fistula presented with a
      relatively recent history of increasing shortness of breath, sputum purulence and
      haemoptysis. Further investigation with a CT scan and bronchoscopy revealed the
      presence of a foreign body within his right lower lobe bronchus which was later
      removed by advancing a flexible bronchoscope over a rigid one. 

PMID- 23861276
TI  - Sepsis mimicking thyroid storm in a patient with methimazole-induced
      agranulocytosis.
AB  - Agranulocytosis is a rare yet life-threatening complication of methimazole
      therapy for hyperthyroidism. We present the case of a 37-year-old female recently
      started on methimazole for hyperthyroidism who presented to our facility for
      evaluation of suspected thyroid storm. In addition to having abnormal thyroid
      indices, she was noted to have an odontogenic abscess, and was septic with
      profound neutropenia. Her symptoms resolved quickly following incision and
      drainage of her abscess and treatment with broad-spectrum antibiotics. Her
      neutrophil count improved significantly following cessation of methimazole and
      administration of granulocyte colony-stimulating factor. Diagnosis was initially
      confounded by the similarity between symptoms of early sepsis and those of
      thyroid storm. This case report discusses the factors leading to diagnostic delay
      and highlights the dangerous manifestations of neutropenia in patients on
      methimazole therapy. 

PMID- 23861277
TI  - Gelatinous bone marrow transformation secondary to unusual eating habits and
      drastic weight loss.
AB  - Gelatinous bone marrow transformation (GMT), also known as starvation bone
      marrow, has been reported in a number of chronic illnesses, eating disorders
      (anorexia nervosa) and malignancies. We report the case of a 37-year-old man with
      a history of bipolar disorder and obesity (weighing >300 pounds) who presented
      due to recently developing a deep yellow colour to his skin. Over the past 2
      years, through diet and exercise, he lost over 150 pounds. He reported running 6
      8 miles per day and eating 'lots of squash'. We made the diagnosis of starvation
      hepatitis and bone marrow degeneration, and referred the patient to a dietician
      and haematologist/oncologist, where improvements were observed at 4 weeks follow
      up. 

PMID- 23861278
TI  - Unusual cause of menorrhagia.

PMID- 23861279
TI  - Rotavirus-infected children with clinically mild encephalopathy with a reversible
      splenial lesion (MERS).

PMID- 23861280
TI  - High dose thiamine improves fatigue in multiple sclerosis.
AB  - The majority of the patients with multiple sclerosis (MS) experience fatigue.
      Some observations indicate that fatigue and related manifestations concomitant
      with MS could be associated with an intracellular mild thiamine deficiency. We
      recruited 15 patients with MS who also experience fatigue and assessed the
      severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine
      and thiamine pyrophosphate levels were within normal limit in all the patients,
      high-dose thiamine therapy administered orally or parenterally led to an
      appreciable improvement of the fatigue. The absence of apparent decrease in blood
      thiamine despite the presence of symptoms referable to a mild thiamine deficiency
      suggests that these patients may have a dysfunction of the mechanisms of
      intracellular transport or structural enzymatic abnormalities. The administration
      of large quantities of thiamine was effective in reversing the fatigue in MS,
      suggesting that the abnormalities in thiamine-dependent processes could be
      overcome by diffusion-mediated transport at supranormal thiamine concentrations. 

PMID- 23861281
TI  - A simple and inexpensive retainer for overdenture prosthesis.
AB  - This article describes a clinical case report of a 65-year-old male patient in
      which an overdenture was fabricated by using a simple, logical and inexpensive
      means of retentive device. The described mandibular overdenture involves a simple
      modification in the coping design and a wire lock mechanism which was fabricated
      during denture processing. The problems associated with copings were overcome by
      putting the patient on a regimen wherein topical fluoride was applied every week
      on the abutment. The denture, fabricated involving a wire lock mechanism, was
      highly retentive and stable. Patient was highly satisfied with the outcome of the
      treatment. 

PMID- 23861282
TI  - Catastrophic antiphospholipid syndrome in childhood: presentation with an
      inferior caval vein mass.
AB  - Venous thromboembolism remains one of the important causes of pulmonary
      hypertension in children. The causes of venous thromboembolism are varied and
      include antiphospholipid antibody syndrome (APS). Catastrophic APS (CAPS) is a
      severe variant of APS characterised by disseminated thrombosis and
      microangiopathy resulting in multiorgan failure. CAPS can occur independently
      (primary APS) but mainly occurs in association with systemic lupus erythematosus
      including the paediatric population. We report a young girl with primary CAPS who
      presented with pulmonary hypertension and an inferior vena cava mass masquerading
      as a tumour. 

PMID- 23861283
TI  - Speech aid prosthesis.
AB  - Velopharyngeal defects are common problem encountered in dentistry, different
      prosthetic designs can be used; however, the prosthesis should be comfortable and
      function properly. Surgical treatment is the treatment of choice, but there are
      few patients who are not able to receive the surgical intervention; in such cases
      prosthetic management is considered using speech bulb prosthesis to overcome
      nasal twang and nasal regurgitation. 

PMID- 23861284
TI  - Laughter-induced syncope.
AB  - This case report describes a 58-year-old man who is otherwise healthy but has
      periodic episodes of syncope which only happen when he laughs vigorously. This
      occurs suddenly with no prodrome, so the patient has no time to react and is
      unable to brace himself when he falls. The case is one of the very few described
      in the medical literature, most of which have similar presentations and findings
      on subsequent investigation. Recognition of the typical presentation, in the
      absence of more serious causes of syncope, may avoid extensive and expensive
      evaluation. 

PMID- 23861286
TI  - Light activation for the versatile and accurate kinetic analysis of disassembly
      of self-immolative spacers.
AB  - Three procedures that rely on photoactivation are introduced to accurately
      analyze the disassembly kinetics of a collection of self-immolative spacer groups
      within the window 10(-2)-10(3) s. Our results are relevant for deriving
      quantitative structure-property relationships. In particular, we have been able
      to access 20 ms temporal resolution, which made possible the measurement of the
      shortest ever reported disassembly time for an activated self-immolative spacer.

PMID- 23861285
TI  - Multifunctional polyelectrolyte microparticles for oral insulin delivery.
AB  - Multicomponent insulin-containing microparticles are prepared by layer-by-layer
      assembly of dextran sulfate and chitosan on the core of protein-polyanion complex
      with or without protease inhibitors. Oral bioavailability of the encapsulated
      insulin is improved due to the cumulative effect of each component. A physico
      chemical study shows that the particle design allows adjustment of the pH
      dependent profile of the insulin release, as well as mucoadhesive properties and
      Ca(2+) binding ability of the microparticles. Supplementing the microparticles
      with 2-3% protease inhibitors fully prevents proteolysis of human insulin. The
      pharmacological effect of microencapsulated insulin in doses 50-100 IU kg(-1) is
      demonstrated in chronic experiments after oral administration to diabetic rats
      fed ad libitum. 

PMID- 23861287
TI  - Porphyrins for probing electrical potential across lipid bilayer membranes by
      second harmonic generation.

PMID- 23861289
TI  - Distribution of mercury and selenium in blood compartments of bottlenose dolphins
      (Tursiops truncatus) from Sarasota Bay, Florida.
AB  - Total mercury and selenium concentrations ([THg], [Se]) in serum, plasma, whole
      blood, and packed cells were examined in a resident population of free-ranging
      bottlenose dolphins (Tursiops truncatus) from Sarasota Bay, Florida, USA. The
      authors determined how these elements partition in blood and assess compartment
      specific associations. Determining the distribution of Se and THg can provide
      physiologic insight into potential association of Hg with selenol-containing
      biomolecules (e.g., antioxidants) in blood compartments. Concentrations of THg
      were ranked serum < plasma < whole blood < packed cells; whereas for Se
      concentrations, plasma < serum < whole blood < packed cells. The Se:THg molar
      ratio was greater than 1 in all compartments, with the higher ratios found in
      serum and plasma (plasma < serum) and the lower in whole blood and packed cells
      (packed cells < whole blood). Age was positively correlated with [THg] in all
      blood compartments and with [Se] in serum, plasma, and whole blood. Age was
      negatively correlated with Se:THg molar ratios in all blood compartments, driven
      by low [THg] in young animals. Although [THg] was highly correlated among all
      blood compartments, this was not the case for [Se]. The feasibility of
      calculating packed cell [THg], [Se], and Se:THg molar ratios using hematocrit
      measurements in combination with whole blood and plasma [THg] and [Se] was
      validated, allowing routine assessment of compartmentalization within
      erythrocytes using standard clinical measurements.

PMID- 23861290
TI  - Tuning excited state isomerization dynamics through ground state structural
      changes in analogous ruthenium and osmium sulfoxide complexes.
AB  - The complexes [Ru(bpy)2(pyESO)](PF6)2 and [Os(bpy)2(pyESO)](PF6)2, in which bpy
      is 2,2'-bipyridine and pyESO is 2-((isopropylsulfinyl)ethyl)pyridine, were
      prepared and studied by (1)H NMR, UV-visible and ultrafast transient absorption
      spectroscopy, as well as by electrochemical methods. Crystals suitable for X-ray
      structural analysis were grown for [Ru(bpy)2(pyESO)](PF6)2. Cyclic voltammograms
      of both complexes provide evidence for S->O and O->S isomerization as these
      voltammograms are described by an ECEC (electrochemical-chemical electrochemical
      chemical) mechanism in which isomerization follows Ru(2+) oxidation and Ru(3+)
      reduction. The S- and O-bonded Ru(3+/2+) couples appear at 1.30 and 0.76 V versus
      Ag/AgCl in propylene carbonate. For [Os(bpy)2(pyESO)](PF6)2, these couples appear
      at 0.97 and 0.32 V versus Ag/AgCl in acetonitrile, respectively. Charge-transfer
      excitation of [Ru(bpy)2(pyESO)](PF6)2 results in a significant change in the
      absorption spectrum. The S-bonded isomer of [Ru(bpy)2(pyESO)](2+) features a
      lowest energy absorption maximum at 390 nm and the O-bonded isomer absorbs at 480
      nm. The quantum yield of isomerization in [Ru(bpy)2(pyESO)](2+) was found to be
      0.58 in propylene carbonate and 0.86 in dichloroethane solution. Femtosecond
      transient absorption spectroscopic measurements were collected for both
      complexes, revealing time constants of isomerizations of 81 ps (propylene
      carbonate) and 47 ps (dichloroethane) in [Ru(bpy)2(pyESO)](2+). These data and a
      model for the isomerizing complex are presented. A striking conclusion from this
      analysis is that expansion of the chelate ring by a single methylene leads to an
      increase in the isomerization time constant by nearly two orders of magnitude.

PMID- 23861288
TI  - Psychological profiles and pain characteristics of older adults with knee
      osteoarthritis.
AB  - OBJECTIVE: To identify psychological profiles in persons with knee osteoarthritis
      (OA) and to determine the relationship between these profiles and specific pain
      and sensory characteristics, including temporal summation and conditioned pain
      modulation. METHODS: Individuals with knee OA (n = 194) completed psychological,
      health, and sensory assessments. Hierarchical cluster analysis was used to derive
      psychological profiles that were compared across several clinical pain/disability
      and experimental pain responses. RESULTS: Cluster 1 had high optimism with low
      negative affect, pain vigilance, anger, and depression, along with the lowest
      self-reported pain/disability and the lowest sensitivity to mechanical, pressure,
      and thermal pain (P < 0.01 for all). Cluster 2 had low positive affect with high
      somatic reactivity, while cluster 3 showed high pain vigilance with low optimism.
      Clusters 2 and 3 had intermediate levels of self-reported pain/disability and
      cluster 3 experienced central sensitization to mechanical stimuli. Participants
      in cluster 3 also displayed significant pain facilitation (P < 0.05). Cluster 4
      exhibited the highest pain vigilance, reactivity, negative affect, anger, and
      depression. These individuals experienced the highest self-reported
      pain/disability, including widespread pain (P < 0.001 for all). Cluster 4 was
      most sensitive to mechanical, pressure, and thermal stimuli, and showed
      significant central sensitization to mechanical and thermal stimuli (P < 0.001
      for all). CONCLUSION: Our findings demonstrate the existence of homogeneous
      psychological profiles displaying unique sets of clinical and somatosensory
      characteristics. Multidisciplinary treatment approaches consistent with the
      biopsychosocial model of pain should provide significant advantages if targeted
      to profiles such as those in our OA sample.

PMID- 23861292
TI  - An unusual porous metal-organic framework that demonstrates the highly efficient
      exchange of metal ions and the reversible adsorption of iodine.
AB  - An exceedingly rare porous metal-organic framework that is based on cadmium ions
      and multi carboxylate ligands, namely, Na(0.25)[(CH3)2NH2](1.75)[Cd(L)2].x
      solvent (1, H2L=2-hydroxymethyl-4,6-bi(2'-methoxyl-4'-(2''-1''-carboxyl)-ethlene)
      1,3,5-mesitylene), has been successfully synthesized under solvothermal
      conditions. Compound 1 exhibits a 2D network that is constructed from left- and
      right-handed helical chains. Furthermore, neighboring 2D layers are stacked to
      give a porous motif. Strikingly, compound 1 exhibits the highly efficient
      exchange of metal ions from the main framework components whilst maintaining the
      structural integrity and the crystallinity of the network. In addition, Compound
      1 also shows outstanding performance in the reversible adsorption of iodine.

PMID- 23861291
TI  - Clinical characteristics and medication uses among fibromyalgia patients newly
      prescribed amitriptyline, duloxetine, gabapentin, or pregabalin.
AB  - OBJECTIVE: Fibromyalgia is a common chronic pain disorder with unclear etiology.
      No definitive treatment is available for fibromyalgia, and treatment with
      antidepressants or antiepileptics is often used for symptom management. METHODS:
      Using US health care utilization data, a large population-based cohort study was
      conducted to describe clinical characteristics and medication use patterns in
      patients diagnosed with fibromyalgia who newly started amitriptyline, duloxetine,
      gabapentin, or pregabalin. RESULTS: There were 13,404 amitriptyline starters,
      18,420 duloxetine starters, 23,268 gabapentin starters, and 19,286 pregabalin
      starters. The mean age ranged from 48-51 years and 72-84% in each group were
      women. Back pain was the most frequent comorbidity in all 4 groups (range 48-64%)
      and hypertension, headache, depression, and sleep disorder were also common. The
      median daily dose at the start of followup was 25 mg for amitriptyline, 60 mg for
      duloxetine, 300 mg for gabapentin, and 75 mg for pregabalin, and >60% of patients
      remained on the same dose throughout the follow up period. Only one-fifth of
      patients continued the treatment started for >=1 year. The mean number of
      different prescription drugs at baseline ranged from 8-10 across the groups. More
      than one-half of patients took opioids and one-third took benzodiazepines, sleep
      disorder drugs, and muscle relaxants. CONCLUSION: Patients who started 1 of the 4
      common drugs for fibromyalgia similarly had multiple comorbidities and other
      fibromyalgia-related medication use, but continued the treatment only for a short
      time. The dose of the 4 drugs was not increased in most patients during the
      followup period.

PMID- 23861293
TI  - No effect of exercise on urinary 6-sulfatoxymelatonin and catecholamines in young
      women participating in a 16-week randomized controlled trial.
AB  - BACKGROUND: Women with breast cancer have decreased levels of melatonin or its
      metabolite in plasma and/or urine. METHODS: We measured serum melatonin, urinary
      6-sulfatoxymelatonin, catecholamines, and cortisol in 141 sedentary young female
      participants in a clinical trial comparing 150 min/wk aerobic exercise for 4
      months to no-exercise controls. Demographics, health surveys, body composition,
      sleep quality, fitness levels, and blood and urine samples were obtained at
      baseline and 16 weeks. RESULTS: There were no differences between groups at
      baseline in demographics, exercise, sleep habits, or study hormones. There were
      also no significant differences between groups in any of the hormones at 16
      weeks. CONCLUSION: Sixteen weeks of exercise had minimal effects on melatonin
      secretion of young women. IMPACT: There is convincing evidence that exercise
      protects against breast cancer, but this does not appear to occur through changes
      in melatonin secretion.

PMID- 23861294
TI  - Synthesis of ent-kaurane and beyerane diterpenoids by controlled fragmentations
      of overbred intermediates.

PMID- 23861295
TI  - Intrauterine infection and post-partum bacteraemia due to Streptococcus
      gallolyticus subsp. pasteurianus.
AB  - The case is presented of a woman with intrauterine infection and post-partum
      bacteraemia due to Streptococcus gallolyticus subsp. pasteurianus, who delivered
      an infant via Caesarean section. Furthermore, we comment on the possibility of
      vaginal colonization of this organism as a portal of entry in cases of maternal
      and neonatal infections. 

PMID- 23861296
TI  - Composition of Escherichia coli population in the neonatal gut: phylogroups and
      virulence determinants.
AB  - The composition of Escherichia coli in the neonatal gut has rarely been studied
      in developing countries. To gain insight into the composition of E. coli in the
      neonatal gut and to assess factors that could influence colonization by E. coli,
      analysis of the phylogenetic groups and virulence determinants of E. coli
      isolated from the guts of neonates in a tertiary care hospital was carried out.
      The distribution of the phylogroups of 124 E. coli isolates recovered showed that
      phylogroups A (23 %) and B1 (49 %) accounted for 72 % of the isolates. Isolates
      of the phylogenetic group B2 were rare (8 %). Virulence factors were also rare
      with the exception of aerobactin (iucC), which was detected in 45 % of the
      isolates and was significantly associated with phylogroup B1. Multinomial
      logistic regression established that colonization with phylogroup B1 was
      associated with a stay in the neonatal intensive care unit; phylogroup A was
      associated with a stay on the ward; and phylogroups B2 and D were associated with
      neonates delivered vaginally. Evaluation of the effect of different E. coli
      phylogroups, with and without identified virulence determinants, on the gut of
      neonatal mice showed histopathological changes in the mucosa. The severity of the
      changes could be correlated with the presence of virulence determinants,
      irrespective of the phylogroup. 

PMID- 23861297
TI  - Staphylococcus epidermidis with the icaA-/icaD-/IS256- genotype and protein or
      protein/extracellular-DNA biofilm is frequent in ocular infections.
AB  - In ocular infections (OIs) caused by Staphylococcus epidermidis, biofilms
      composed mainly of poly-N-acetylglucosamine (PNAG) have been widely studied, but
      PNAG-independent biofilms have not. Therefore, we searched for a relationship
      between the ica operon (involved in PNAG-biofilm) and the biochemical composition
      of biofilms in isolates from OI. Isolates from OI (n = 62), from healthy
      conjunctiva (HC; n = 45) and from healthy skin (HS; n = 53), were used to detect
      icaA and icaD genes, and the insertion sequence 256 (IS256) using PCR. The
      compositions of the biofilms were determined by treatment with NaIO4, proteinase
      K and DNase I. Multilocus sequence typing (MLST) was performed to characterize
      the isolates, and the expression of aap and embp genes was determined by real
      time qPCR. A strong relationship between the icaA(-)/icaD(-)/IS256(-) genotype
      and protein- or protein/extracellular DNA (eDNA)-biofilm composition was found in
      the isolates from OI (53.6%), whereas the icaA(+)/icaD(+)/IS256(-) genotype and
      carbohydrate-biofilm was most prevalent in isolates from HC (25%) and HS (25%).
      Isolates with an icaA(-)/icaD(-)/IS256(-) genotype and protein-biofilm phenotype
      were predominantly of the ST2 lineage, while carbohydrate-biofilm-producing
      strains were mainly of the ST9 lineage. The protein-biofilm-producing strains had
      higher expression levels of aap gene than carbohydrate-biofilm-producing strains;
      while embp gene did not have the same pattern of expression. These results
      suggest that S. epidermidis strains with icaA(-)/icaD(-)/IS256(-) genotype and
      protein- or protein/eDNA-biofilms have a stronger ability to establish in the eye
      than S. epidermidis strains with icaA(+)/icaD(+)/IS256(-) genotype and PNAG
      biofilms.

PMID- 23861298
TI  - Antimicrobial susceptibility of animal and human isolates of Clostridium
      difficile by broth microdilution.
AB  - A total of 188 human (n = 92) and animal (n = 96) isolates of Clostridium
      difficile of different PCR ribotypes were screened for susceptibility to 30
      antimicrobials using broth microdilution. When comparing the prevalence of
      antimicrobial resistance, the isolates of animal origin were significantly more
      often resistant to oxacillin, gentamicin and trimethoprim/sulfamethoxazole
      (P<0.01). The most significant difference between the animal and human
      populations (P = 0.0006) was found in the level of imipenem resistance, with a
      prevalence of 53.3 % in isolates of human origin and 28.1 % in isolates of animal
      origin. Overall, the results show similar MICs for the majority of tested
      antimicrobials for isolates from human and animal sources, which were collected
      from the same geographical region and in the same time interval. This supports
      the hypothesis that C. difficile could be transmissible between human and animal
      hosts. Resistant isolates have been found in all animal species tested, including
      food and companion animals, and also among non-toxigenic isolates. The isolates
      of the most prevalent PCR ribotype 014/020 had low resistance rates for
      moxifloxacin, erythromycin, rifampicin and daptomycin, but a high resistance rate
      for imipenem. Multiresistant strains were found in animals and humans, belonging
      to PCR ribotypes 012, 017, 027, 045, 046, 078 and 150, and also to non-toxigenic
      strains of PCR ribotypes 010 and SLO 080.

PMID- 23861299
TI  - Mapping SAGE questionnaire to the International Classification of Functioning,
      Disability and Health (ICF).
AB  - The collaborative research on ageing in Europe protocol was based on that of the
      World Health Organization Study on global AGEing and adult health (SAGE) project
      that investigated the relationship between health and well-being and provided a
      set of instruments that can be used across countries to monitor health and health
      related outcomes of older populations as well as the strategies for addressing
      issues concerning the ageing process. To evaluate the degree to which SAGE
      protocol covered the spectrum of disability given the scope of the World Health
      Organization International Classification of Functioning, Disability and Health
      (ICF), a mapping exercise was performed with SAGE protocol. Results show that the
      SAGE protocol covers ICF domains in a non-uniform way, with environmental factors
      categories being underrepresented, whereas mental, cardiovascular, sensory
      functions and mobility were overrepresented. To overcome this partial coverage of
      ICF functioning categories, new assessment instruments have been developed.
      PRACTITIONER MESSAGE: Mapping exercises are valid procedures to understand the
      extent to which a survey protocol covers the spectrum of functioning. The mapping
      exercise with SAGE protocol shows that it provides only a partial representation
      of body functions and activities and participation domains, and the coverage of
      environmental factors is poor. New instruments are therefore needed for
      researchers to properly understand the health and disability of ageing
      populations.

PMID- 23861300
TI  - Plasma concentrations of organohalogenated pollutants in predatory bird
      nestlings: associations to growth rate and dietary tracers.
AB  - The extent to which persistent organic pollutants (POPs) with different
      physicochemical properties originated from the food (dietary input) was assessed
      in raptor nestlings. Lipophilic polychlorinated biphenyl (PCB) 153, 1-dichloro
      2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), and hexachlorobenzene (HCB), and
      protein-bound perfluorooctane sulfonate (PFOS), were measured repeatedly in blood
      plasma of individual goshawk (Accipiter gentilis) and white-tailed eagle
      (Haliaeetus albicilla) nestlings, 1 to 3 wk after hatching and near fledging.
      Maternally derived POPs dilute as nestlings grow (growth dilution), and
      increasing plasma concentrations would indicate dietary input. First, plasma
      concentrations given no dietary input were estimated, and concentrations of p,p'
      DDE, HCB, and notably PFOS were significantly higher than predicted from a growth
      dilution scenario (approximately 1.5-fold to 2.5-fold higher; p < 0.001). In
      contrast, PCB 153 declined in both species, although concentrations were still
      higher than predicted in white-tailed eagle nestlings (p < 0.05). Second, the
      relationships between plasma POP concentrations and trophic position (delta(15)
      N) and dietary carbon source (delta(13) C) were analyzed, controlling for growth
      rate. Both delta(15) N and delta(13) C (measured in body feathers) were
      significantly associated to the accumulation of most POPs, except PFOS. In
      conclusion, pollutant data acquired in plasma of nestling raptors should be
      interpreted and further investigated in the light of individual feeding ecology,
      and the use of raptor nestlings as sentinels for POP monitoring could be
      optimized by correcting for different factors such as body condition, brood size,
      and age.

PMID- 23861301
TI  - Endogenous morphine-6-glucuronide (M6G) is present in the plasma of patients:
      validation of a specific anti-M6G antibody for clinical and basic research.
AB  - Endogenous morphine and its derivatives (morphine-6-glucuronide [M6G]; morphine-3
      glucuronide [M3G]) are formed by mammalian cells from dopamine. Changes in the
      concentrations of endogenous morphine have been demonstrated in several
      pathologies (sepsis, Parkinson's disease, etc.), and they might be relevant as
      pathological markers. While endogenous morphine levels are detectable using
      enzyme-linked immunosorbant assay (ELISA), mass spectrometry (MS) analysis was,
      so far, the only approach to detect and quantify M6G. This study describes the
      preparation of a specific anti-M6G rabbit polyclonal antibody and its validation.
      The specificity of this antibody was assessed against 30 morphine-related
      compounds. Then, a M6G-specific ELISA-assay was tested to quantify M6G in the
      plasma of healthy donors, morphine-treated, and critically ill patients. The
      antibody raised against M6G displays a strong affinity for M6G, codeine-6
      glucuronide, and morphine-3-6-glucuronide, whereas only weak cross-reactivities
      were observed for the other compounds. Both M6G-ELISA and LC-MS/MS approaches
      revealed the absence of M6G in the plasma of healthy donors (controls, n = 8). In
      all positive donors treated with morphine-patch (n = 5), M6G was detected using
      both M6G-ELISA and LC-MS/MS analysis. Finally, in a study on critically ill
      patients with circulating endogenous morphine (n = 26), LC-MS/MS analysis
      revealed that 73% of the positive-patients (19 of 26), corresponding to high M6G
      levels in M6G-ELISA, contained M6G. In conclusion, we show that endogenous M6G
      can be found at higher levels than morphine in the blood of morphine-naive
      patients. With respect to the interest of measuring endogenous M6G in
      pathologies, we provide evidences that our ELISA procedure represents a powerful
      tool as it can easily and specifically detect endogenous M6G levels.

PMID- 23861302
TI  - 3D-ultramicroscopy utilizing aspheric optics.
AB  - Using a combination of achromatic aspheric optical elements and achromatic
      cylindrical lenses, we developed an improved laser light sheet generator for two
      side illumination ultramicroscopy. This light sheet generator has a much longer
      Rayleigh range, a more uniform spatial intensity distribution along x -, y - and
      z-axis, and reduced aberrations than the standard system consisting of a slit
      aperture and a single cylindrical lens, which is commonly used in light sheet
      microscopy. As there is no truncation of the beam by a slit aperture in our
      design the laser energy is used more efficiently. Applying this light sheet
      generator to ultramicroscopy of chemically cleared biological samples, such as
      Drosophila, dissected mouse hippocampi, and entire mouse brains, we achieved a
      markedly improved resolution of fine details.

PMID- 23861304
TI  - Isolation of neutral mono- and dinuclear gold complexes of cyclic
      (alkyl)(amino)carbenes.

PMID- 23861303
TI  - Golimumab, a human anti-tumor necrosis factor monoclonal antibody, injected
      subcutaneously every 4 weeks in patients with active rheumatoid arthritis who had
      never taken methotrexate: 1-year and 2-year clinical, radiologic, and physical
      function findings of a phase III, multicenter, randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: To assess 2-year golimumab efficacy/safety in patients with active
      rheumatoid arthritis (RA) who had never taken methotrexate (MTX). METHODS: RA
      patients who had never taken MTX (n = 637) were randomized (1:1:1:1) to placebo +
      MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group
      3), or golimumab 100 mg + MTX (group 4) every 4 weeks. Nonresponders based on
      week 28 swollen/tender joint counts changed treatment as follows: group 1 added
      golimumab 50 mg, group 2 added MTX, group 3 increased golimumab to 100 mg, and
      group 4 had no change. Most group 1 patients (85%) initiated golimumab 50 mg +
      MTX at week 28 or subsequently at week 52. After the last patient completed week
      52 and blinding was broken, the investigator could escalate golimumab to 100 mg
      and/or adjust MTX. The co-primary end points (week 24 American College of
      Rheumatology criteria for 50% improvement [ACR50] response and week 52 change in
      Sharp/van der Heijde score [SHS]) have been published previously. We now detail
      week 52 major secondary end points (Health Assessment Questionnaire [HAQ]
      disability index [DI] scores and SHS among patients with a baseline C-reactive
      protein [CRP] level >1.0 mg/dl) and week 104 findings. RESULTS: At week 52 for
      combined groups 3 and 4 versus group 1, the respective proportions of patients
      achieving ACR20 and ACR50 responses were 63.2% versus 51.9% (P = 0.017) and 45.3%
      versus 35.6% (P = 0.044). Respective week 52 mean HAQ DI improvements were 0.70
      versus 0.58 (P = 0.053); mean SHS changes were 0.41 versus 1.37 (P = 0.006) among
      all patients and 0.74 versus 2.16 (P = 0.003) in patients with a CRP level >1.0
      mg/dl. Improvements were maintained through week 104. Golimumab + MTX for 2 years
      yielded statistically less radiographic progression than initial MTX or golimumab
      100 mg monotherapy. Golimumab safety profiles through weeks 24, 52, and 104 were
      generally consistent with those observed in other golimumab studies. CONCLUSION:
      In RA patients who had never taken MTX, up to 2 years of golimumab + MTX yielded
      sustained improvements in clinical signs/symptoms, physical function, and
      radiographic progression.

PMID- 23861305
TI  - Design, synthesis and bioactivity evaluation of novel benzophenone hydrazone
      derivatives.
AB  - BACKGROUND: Benzophenone hydrazone derivatives are among the most important
      classes of synthetic insecticides. In an effort to discover new molecules with
      good insecticidal/acaricidal activities, a series of novel benzophenone hydrazone
      N-acylated thiourea and urea derivatives was synthesized and bioassayed. RESULTS:
      All of these compounds exhibited excellent bioactivities against T. cinnabarinus
      and B. brassicae, especially towards T. cinnabarinus with LC50 values ranging
      from 0.305 to 2.036 mmol L(-1). Moreover, the acaricidal activities against T.
      cinnabarinus of compounds 8a-i, 12b-f and 12h were 2.5-5.5-fold that of parent
      molecule 3 based on the LC50 value. CONCLUSION: Based on the observed
      bioactivities, the structure-activity relationship of these analogs was also
      discussed. Structure-activity relationships provided information that could
      direct further investigation on structure modification. Our studies indicated
      that benzophenone hydrazone N-acylated thiourea and urea derivatives could be
      used as potential lead compounds for developing novel acaricides and
      insecticides.

PMID- 23861306
TI  - Validation of the COURAGE Built Environment Self-Reported Questionnaire.
AB  - The built environment (BE) impacts on people's disability and health, in terms of
      overweight, depression, alcohol abuse, poor self-rated health and presence of
      psychological symptoms; it is reasonable to assume that BE also impacts on
      participation levels. This paper presents the validation of the COURAGE Built
      Environment Self-Reported Questionnaire (CBE-SR), an instrument designed to
      evaluate BE in the context of health and disability. Subjects participating to
      COURAGE, a cross-sectional study conducted on 10,800 citizens of Poland, Finland
      and Spain, completed a protocol inclusive of the CBE-SR. Psychometric properties
      and factor structure were analysed, and factor scores created. Gender
      differences, differences between persons from different age groups and persons
      reporting the environment as facilitating, hindering or neutral were calculated.
      Eight items were deleted so that the final version of CBE-SR comprises 19 items.
      Cronbach's alpha ranged from 0.743 to 0.906, and test-retest stability was
      demonstrated for the majority of items. Four subscales were identified: Usability
      of the neighbourhood environment; Hindrance of walkable environment; Easiness of
      use of public buildings, places and facilities; and Risk of accidents and
      usability of the living place. Younger respondents reported their neighbourhood
      as more usable but perceived walkways as more hindering and public buildings as
      less easy to use; gender differences were almost inexistent. The CBE-SR is a four
      scale instrument with good psychometric properties that measures the person
      environment interaction. It is sensitive across age groups and is consistent with
      the subject's overall judgement of the degree to which the environment is
      facilitating or hindering. KEY PRACTITIONER MESSAGE: Poor built environments have
      a negative impact on the level of a person's participation. However, instruments
      measuring the person-environment interaction are lacking. The CBE-SR is a valid
      and reliable instrument that researchers can use to assess the relationships
      between the intrinsic health state and the objective features of the environment.
      Understanding this relationship would provide further insight into the need of
      addressing the individual's functioning either by means of interventions directed
      to the individual or by making changes to the individual's environment.

PMID- 23861307
TI  - Physiology and transcriptome of the polycyclic aromatic hydrocarbon-degrading
      Sphingomonas sp. LH128 after long-term starvation.
AB  - The survival, physiology and gene expression profile of the phenanthrene
      degrading Sphingomonas sp. LH128 was examined after an extended period of
      complete nutrient starvation and compared with a non-starved population that had
      been harvested in exponential phase. After 6 months of starvation in an isotonic
      solution, only 5 % of the initial population formed culturable cells. Microscopic
      observation of GFP fluorescent cells, however, suggested that a larger fraction
      of cells (up to 80 %) were still alive and apparently had entered a viable but
      non-culturable (VBNC) state. The strain displayed several cellular and genetic
      adaptive strategies to survive long-term starvation. Flow cytometry, microscopic
      observation and fatty acid methyl ester (FAME) analysis showed a reduction in
      cell size, a change in cell shape and an increase in the degree of membrane fatty
      acid saturation. Transcriptome analysis showed decreased expression of genes
      involved in ribosomal protein biosynthesis, chromosomal replication, cell
      division and aromatic catabolism, increased expression of genes involved in
      regulation of gene expression and efflux systems, genetic translocations, and
      degradation of rRNA and fatty acids. Those phenotypic and transcriptomic changes
      were not observed after 4 h of starvation. Despite the starvation situation, the
      polycyclic aromatic hydrocarbon (PAH) catabolic activity was immediate upon
      exposure to phenanthrene. We conclude that a large fraction of cells maintain
      viability after an extended period of starvation apparently due to tuning the
      expression of a wide variety of cellular processes. Due to these survival
      attributes, bacteria of the genus Sphingomonas, like strain LH128, could be
      considered as suitable targets for use in remediation of nutrient-poor PAH
      contaminated environments. 

PMID- 23861308
TI  - Effect of drug treatment options on the mobility and expression of blaKPC.
AB  - OBJECTIVES: Both transposition and increases in gene expression have been
      implicated in the success of KPC-producing pathogens, but the stimulus required
      for these phenomena are unknown. It is possible that exposure to antimicrobials
      during patient treatment increases bla(KPC) expression or induces Tn4401
      transposition. The purpose of this study was to determine if exposure to
      carbapenems or other antimicrobial drug classes could stimulate expression of
      bla(KPC) or the in vitro transposition of Tn4401. METHODS: Five KPC-producing
      clinical isolates were evaluated in this study. Gene expression of RNA from each
      isolate exposed to subinhibitory, MIC or suprainhibitory levels of antibiotics
      was evaluated using real-time RT-PCR. Southern blots were performed on plasmids
      from isolates exposed to subinhibitory levels of antibiotics. RESULTS: There were
      subtle changes in bla(KPC) RNA expression following antibiotic exposure that were
      both strain and drug dependent. Multiple plasmids ranging from ~8 to >200 kb were
      observed for the Enterobacteriaceae isolates, whereas the Pseudomonas aeruginosa
      isolate had one ~55 kb plasmid. No changes in hybridization patterns or binding
      intensity for the bla(KPC) probe were observed after antibiotic exposure.
      CONCLUSIONS: While the changes in bla(KPC) RNA expression are subtle, the
      different responses observed suggest both strain- and genera-specific variations
      in response to different antibiotic treatments.

PMID- 23861309
TI  - In vivo selection of a complex mutant TEM (CMT) from an inhibitor-resistant TEM
      (IRT) during ceftazidime therapy.
AB  - OBJECTIVES: A relapse from Escherichia coli bloodstream infection was observed in
      a patient with acute leukaemia treated with ceftazidime for 7 days for febrile
      neutropenia. Whereas the original E. coli isolate was resistant to beta
      lactam/beta-lactamase inhibitor combinations (EC1), the relapse E. coli isolate
      showed a similar phenotype but with resistance extended to ceftazidime (EC2). We
      investigated the molecular mechanisms of beta-lactam resistance and sought if EC2
      could have been selected in vivo from EC1. METHODS: EC1 and EC2 isolates were
      compared for antibiotic MICs, plasmid content, genotyping, beta-lactamase genes
      and their environment. Both isolates were conjugated with E. coli JW4111DeltaampC
      and MICs determined for transconjugants. In addition, ceftazidime-resistant
      mutants were selected in vitro from EC1. RESULTS: EC1 and EC2 showed identical
      patterns for genotyping and resistance plasmids. PCR sequencing of blaTEM in EC1
      showed the mutations M69L and N276D corresponding to TEM-35, also called
      inhibitor-resistant TEM (IRT)-4. In EC2, the TEM allele showed an additional
      mutation, R164S, known to confer resistance to ceftazidime. The combination of
      these three mutations was previously reported in TEM-158, described as the
      complex mutant TEM (CMT)-9, associated with resistance to beta-lactamase
      inhibitors and third-generation cephalosporins. In vitro selection of ceftazidime
      resistant mutants from EC1 yielded six different CMT alleles, including TEM-158
      containing the R164S mutation. CONCLUSIONS: This first known report of in vivo
      selection of CMT from IRT, reproduced in vitro, shows how the evolution of beta
      lactamase enzymes is easily driven by antibiotic pressure, even during a short
      antibiotic therapy.

PMID- 23861310
TI  - Spread of multidrug-resistant Enterococcus to animals and humans: an
      underestimated role for the pig farm environment.
AB  - OBJECTIVES: The aim of this study was to discover the potential role of the pig
      farm environment in the spread of multidrug-resistant (MDR) Enterococcus strains,
      including high-risk clones, to animals and humans. METHODS: Enterococcus isolates
      were recovered from a variety of samples (n = 82; swine,
      feed/medicines/antiseptics and pig farm facilities) from six Portuguese farms,
      most using antibiotics. Antimicrobial susceptibility/conjugation assays were
      performed by standard procedures, bacterial identification/screening of
      antibiotic resistance genes were performed by PCR and clonality was determined
      using PFGE/multilocus sequence typing. RESULTS: Enterococcus isolates resistant
      to antibiotics (n= 473) were recovered from samples of different origin (swine,
      feed/antiseptics, animal residues and pig farm facilities), but only the
      clinically relevant species Enterococcus faecium (n = 171) and Enterococcus
      faecalis (n = 78) were included for further comprehensive molecular analysis.
      Isolates resistant to vancomycin, ampicillin, tetracyclines, erythromycin and
      aminoglycosides were better recovered in Slanetz-Bartley medium with these
      antibiotics present than in media not supplemented with antibiotics (P < 0.05).
      E. faecium was more frequently resistant to ampicillin, ciprofloxacin or
      nitrofurantoin and E. faecalis to tetracyclines, chloramphenicol or
      aminoglycosides (P < 0.05). Glycopeptide and erythromycin resistance rates were
      similar in both species. The transfer of resistance to several antibiotics,
      including vancomycin and ampicillin, was demonstrated. Clones associated with
      human infections were detected in different samples from the same farm [E.
      faecium from sequence type (ST) 78 lineage and E. faecalis ST16; manure, waste
      lagoons, faeces and drinking water] and in geographically distant farms [E.
      faecium clonal complex (CC) 5; E. faecalis CC21 and ST16]. CONCLUSIONS: The pig
      farm environment has an underestimated potential role in the transmission of MDR
      Enterococcus to animals and, possibly, to humans. The continuous contact of swine
      with MDR Enterococcus by different routes (e.g. feed, dust, air and rooms) might
      decrease the impact of restrictive antibiotic use policies and reinforces the
      need for different and preliminary interventions at the husbandry management
      level.

PMID- 23861311
TI  - In vitro activity of miltefosine as a single agent and in combination with
      voriconazole or posaconazole against uncommon filamentous fungal pathogens.
AB  - OBJECTIVES: Antifungal treatment of uncommon filamentous fungal infections is
      problematic. This study determined the in vitro susceptibility of miltefosine, as
      a single agent and in combination with posaconazole or voriconazole, against
      these pathogens. METHODS: Susceptibility to miltefosine of 34 uncommon
      filamentous fungi was tested using CLSI broth microdilution M38-A2 methodology.
      Twenty isolates were studied for potential synergy using miltefosine/posaconazole
      and miltefosine/voriconazole combinations and the chequerboard microdilution
      assay. RESULTS: MICs of miltefosine were high (in general, >8 mg/L) for most
      isolates compared with amphotericin B, echinocandins and the azoles. Miltefosine
      had greatest activity against Scedosporium spp., Lichtheimia corymbifera and
      Rhizomucor sp. (MICs <= 4 mg/L). Miltefosine in combination either with
      posaconazole or voriconazole demonstrated synergy [fractional inhibitory
      concentration index (FICI) <= 0.5] in 12 instances (11 isolates):
      miltefosine/posaconazole combinations were synergistic against 3 of 4 Fusarium
      oxysporum strains (FICI range 0.37-0.5) and 5 of 10 mucormycete strains (FICI
      range 0.06-0.5). The combination of voriconazole with miltefosine showed synergy
      against one Scedosporium prolificans isolate and three mucormycetes-a single
      strain each of L. corymbifera, Rhizopus oryzae and Rhizomucor sp. No antagonism
      was observed. CONCLUSIONS: Miltefosine demonstrated synergy in 8/20 (40%) and
      4/20 (20%) instances when combined with posaconazole and voriconazole,
      respectively. Synergy was most often observed against F. oxysporum and the
      mucormycetes. Study of miltefosine/azole combinations as a novel antifungal
      approach is indicated.

PMID- 23861312
TI  - Do preoperative urodynamics still have a role in female stress urinary
      incontinence? Re: van Leijsen SA, Kluivers KB, Mol BW, et al. Can preoperative
      urodynamic investigation be omitted in women with stress urinary incontinence? A
      non-inferiority randomized controlled trial. Neurourol Urodyn 2012;31:1118-23.

PMID- 23861313
TI  - Characterization of collagen and cholesterol deposition in atherosclerotic
      arterial tissue using non-linear microscopy.
AB  - Atherosclerosis is characterized by the accumulation of lipids within the
      arterial wall and is commonly diagnosed using standard histology. Non-linear
      microscopy represents a possible label-free alternative to standard diagnostic
      methods for imaging various tissue components. Here we employ SHG and CARS
      microscopy for imaging thin cross-sections of atherosclerotic arterial tissue,
      demonstrating that both cholesterol deposition in the lumen and collagen in the
      normal arterial wall can be imaged and discriminated using SHG and CARS
      microscopy. A simultaneous detection of both forward and backward scattered SHG
      signals allows distinguishing collagen fibres from cholesterol. Further analysis,
      based on image pattern evaluation algorithms, is used to characterize collagen
      organization in the healthy arterial wall against collagen found within plaques.
      Different values of fibre mean size, distribution and anisotropy are calculated
      for lumen and media prospectively allowing for automated classification of
      atherosclerotic lesions. The presented method represents a promising diagnostic
      tool for evaluating atherosclerotic tissue.

PMID- 23861314
TI  - Differential effects of resveratrol and its natural analogs, piceatannol and
      3,5,4'-trans-trimethoxystilbene, on anti-inflammatory heme oxigenase-1 expression
      in RAW264.7 macrophages.
AB  - Resveratrol (Res) and its two natural analogs that are also related to Res
      metabolism, piceatannol (Pic) and 3,5,4'-trans-trimethoxystilbene (TMS), were
      compared in their ability to suppress lipopolysaccharide (LPS)-induced production
      of proinflammatory tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta
      (IL-1beta) and to induce anti-inflammatory heme oxygenase-1 (HO-1) expression in
      RAW264.7 macrophages. At non-cytotoxic concentrations, they differentially
      suppressed LPS-induced production of TNF-alpha and IL-1beta; the relative potency
      for suppression of TNF-alpha and IL-1beta production was Pic > Res > TMS. Res and
      Pic differentially induced HO-1 expression; Pic, which possesses four hydroxyl
      groups, was more active in inducing HO-1 expression than Res that contains three
      hydroxyl groups. TMS, which has none of hydroxyl groups, failed to induce HO-1
      expression. These findings suggest that the hydroxyl groups of Res analogs are
      important for suppression of TNF-alpha and IL-1beta production and HO-1
      expression. Interestingly, protoporphyrin-IX, a competitive inhibitor of HO-1
      activity, partly attenuated the inhibitory effects of Res and Pic (but not TMS)
      on TNF-alpha and IL-1beta production, suggesting that suppression of TNF-alpha
      and IL-1beta production correlates at least in part with HO-1 expression.
      Overall, the ability of Res analogs to induce HO-1 expression may provide one of
      possible mechanisms of their anti-inflammatory action.

PMID- 23861315
TI  - "Somebody to say 'come on we can sort this'": a qualitative study of primary care
      consultation among older adults with symptomatic foot osteoarthritis.
AB  - OBJECTIVE: To examine the experiences of primary care consultation among older
      adults with symptomatic foot osteoarthritis (OA). METHODS: Eleven participants (6
      women and 5 men) ages 56-80 years who had radiographically confirmed symptomatic
      foot OA and consulted a general practitioner in the last 12 months for foot pain
      were purposively sampled. Semistructured interviews explored the nature of the
      foot problem, help-seeking behaviors, and consultation experiences. Verbatim
      transcripts were analyzed using interpretative phenomenological analysis.
      RESULTS: The decision to consult a physician was often the outcome of a complex
      process influenced by quantitative and qualitative changes in symptoms,
      difficulty maintaining day-to-day roles and responsibilities and the effect this
      had on family and work colleagues, and a reluctance to present a fragile or aging
      self to the outside world. Self-management was commonly negotiated alongside
      multimorbidities. Upon seeking help, participants often believed they received
      limited information, they were given a brief or even cursory assessment, and that
      treatment was focused on the prescription of analgesic drugs. CONCLUSION: This is
      the first qualitative study of primary care experiences among patients with
      symptomatic foot OA. The experience of primary care seldom appeared to move
      beyond a label of arthritis and an unwelcome emphasis on pharmacologic treatment.

PMID- 23861316
TI  - Acaricidal activities of beta-caryophyllene oxide and structural analogues
      derived from Psidium cattleianum oil against house dust mites.
AB  - BACKGROUND: This study was to evaluate the acaricidal activities of an active
      compound isolated from Psidium cattleianum and structural analogues against
      Dermatophagoides farinae and D. pteronyssinus. beta-Caryophyllene oxide was
      isolated using chromatographic techniques. RESULTS: Based on the 50% lethal
      concentration (LD50) values against D. farinae using the fumigant method, beta
      caryophyllene oxide (1.36 ug cm(-2)) was ~ 7.52 times more toxic than benzyl
      benzoate (10.23 ug cm(-2)), followed by alpha-caryophyllene (1.75 ug cm(-2)) and
      beta-caryophyllene (3.13 ug cm(-2)). Against D. pteronyssinus, beta-caryophyllene
      oxide (1.38 ug cm(-2)) was ~ 7.22 times more toxic than benzyl benzoate (9.96 ug
      cm(-2)), followed by alpha-caryophyllene (1.71 ug cm(-2)) and beta-caryophyllene
      (3.58 ug cm(-2)). In the contact toxicity method against D. farinae, beta
      caryophyllene oxide (0.44 ug cm(-2)) was ~ 17.27 times more active than benzyl
      benzoate (7.60 ug cm(-2)), followed by alpha-caryophyllene (0.67 ug cm(-2)) and
      beta-caryophyllene (0.91 ug cm(-2)). Against D. pteronyssinus, beta-caryophyllene
      oxide (0.47 ug cm(-2)) was ~ 13.06 times more effective than benzyl benzoate
      (6.14 ug cm(-2)), followed by alpha-caryophyllene (1.71 ug cm(-2)) and beta
      caryophyllene (3.58 ug cm(-2)). CONCLUSION: beta-Caryophyllene oxide and
      structural analogues have potential for development as preventive agents for the
      control of house dust mites.

PMID- 23861317
TI  - Cobalt-catalyzed intramolecular olefin hydroarylation leading to
      dihydropyrroloindoles and tetrahydropyridoindoles.

PMID- 23861318
TI  - Spatiotemporal brain dynamics of emotional face processing modulations induced by
      the serotonin 1A/2A receptor agonist psilocybin.
AB  - Emotional face processing is critically modulated by the serotonergic system. For
      instance, emotional face processing is impaired by acute psilocybin
      administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the
      spatiotemporal brain mechanisms underlying these modulations are poorly
      understood. Here, we investigated the spatiotemporal brain dynamics underlying
      psilocybin-induced modulations during emotional face processing. Electrical
      neuroimaging analyses were applied to visual evoked potentials in response to
      emotional faces, following psilocybin and placebo administration. Our results
      indicate a first time period of strength (i.e., Global Field Power) modulation
      over the 168-189 ms poststimulus interval, induced by psilocybin. A second time
      period of strength modulation was identified over the 211-242 ms poststimulus
      interval. Source estimations over these 2 time periods further revealed decreased
      activity in response to both neutral and fearful faces within limbic areas,
      including amygdala and parahippocampal gyrus, and the right temporal cortex over
      the 168-189 ms interval, and reduced activity in response to happy faces within
      limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our
      results indicate a selective and temporally dissociable effect of psilocybin on
      the neuronal correlates of emotional face processing, consistent with a
      modulation of the top-down control. 

PMID- 23861319
TI  - The neural correlates of upper limb motor blocks in Parkinson's disease and their
      relation to freezing of gait.
AB  - Due to basal ganglia dysfunction, bimanual motor performance in Parkinson
      patients reportedly relies on compensatory brain activation in premotor-parietal
      cerebellar circuitries. A subgroup of Parkinson's disease (PD) patients with
      freezing of gait (FOG) may exhibit greater bimanual impairments up to the point
      that motor blocks occur. This study investigated the neural mechanisms of upper
      limb motor blocks and explored their relation with FOG. Brain activation was
      measured using functional magnetic resonance imaging during bilateral finger
      movements in 16 PD with FOG, 16 without FOG (PD + FOG and PD - FOG), and 16
      controls. During successful movement, PD + FOG showed decreased activation in
      right dorsolateral prefrontal cortex (PFC), left dorsal premotor cortex (PMd), as
      well as left M1 and bilaterally increased activation in dorsal putamen, pallidum,
      as well as subthalamic nucleus compared with PD - FOG and controls. On the
      contrary, upper limb motor blocks were associated with increased activation in
      right M1, PMd, supplementary motor area, and left PFC compared with successful
      movement, whereas bilateral pallidum and putamen activity was decreased. Complex
      striatofrontal activation changes may be involved in the difficulties of PD + FOG
      to perform bimanual movements, or sequential movements in general. These novel
      results suggest that, whatever the exact underlying cause, PD + FOG seem to have
      reached a saturation point of normal neural compensation and respond belatedly to
      actual movement breakdown. 

PMID- 23861320
TI  - Large, male germ cell-specific hypomethylated DNA domains with unique genomic and
      epigenomic features on the mouse X chromosome.
AB  - To understand the epigenetic regulation required for germ cell-specific gene
      expression in the mouse, we analysed DNA methylation profiles of developing germ
      cells using a microarray-based assay adapted for a small number of cells. The
      analysis revealed differentially methylated sites between cell types tested.
      Here, we focused on a group of genomic sequences hypomethylated specifically in
      germline cells as candidate regions involved in the epigenetic regulation of
      germline gene expression. These hypomethylated sequences tend to be clustered,
      forming large (10 kb to ~9 Mb) genomic domains, particularly on the X chromosome
      of male germ cells. Most of these regions, designated here as large
      hypomethylated domains (LoDs), correspond to segmentally duplicated regions that
      contain gene families showing germ cell- or testis-specific expression, including
      cancer testis antigen genes. We found an inverse correlation between DNA
      methylation level and expression of genes in these domains. Most LoDs appear to
      be enriched with H3 lysine 9 dimethylation, usually regarded as a repressive
      histone modification, although some LoD genes can be expressed in male germ
      cells. It thus appears that such a unique epigenomic state associated with the
      LoDs may constitute a basis for the specific expression of genes contained in
      these genomic domains.

PMID- 23861321
TI  - Increased bioplastic production with an RNA polymerase sigma factor SigE during
      nitrogen starvation in Synechocystis sp. PCC 6803.
AB  - Because cyanobacteria directly harvest CO2 and light energy, their carbon
      metabolism is important for both basic and applied sciences. Here, we show that
      overexpression of the sigma factor sigE in Synechocystis sp. PCC 6803 widely
      changes sugar catabolism and increases production of the biodegradable polyester
      polyhydroxybutyrate (PHB) during nitrogen starvation. sigE overexpression
      elevates the levels of proteins implicated in glycogen catabolism, the oxidative
      pentose phosphate pathway, and polyhydroxyalkanoate biosynthesis. PHB
      accumulation is enhanced by sigE overexpression under nitrogen-limited
      conditions, yet the molecular weights of PHBs synthesized by the parental glucose
      tolerant and sigE overexpression strain are similar. Although gene expression
      induced by nitrogen starvation is changed and other metabolites (such as GDP
      mannose and citrate) accumulate under sigE overexpression, genetic engineering of
      this sigma factor altered the metabolic pathway from glycogen to PHB during
      nitrogen starvation. 

PMID- 23861323
TI  - Exercise/physical activity and weight management efforts in Canadians with self
      reported arthritis.
AB  - OBJECTIVE: To describe the exercise/physical activity and weight management
      efforts of Canadians with self-reported arthritis, to examine factors associated
      with their engagement in these strategies to help manage their arthritis, and to
      explore reasons for lack of engagement. METHODS: Data were from the arthritis
      component of the 2009 Survey on Living with Chronic Diseases in Canada. The
      responses (78% response rate; n = 4,565) were weighted to be representative of
      Canadians (ages >=20 years) with arthritis. Logistic regression analyses were
      used to examine factors associated with engaging in exercise/physical activity
      and weight control/loss (among overweight/obese respondents) for arthritis
      management purposes. RESULTS: Individuals with arthritis were mostly women (63%),
      ages >=45 years (89%), overweight/obese (67%), married (68%), and white (87%),
      with postsecondary education (69%). Sixty-three percent were exercising and of
      those who were overweight or obese, 68% were trying to control/lose weight; only
      46% were engaged in both. Having received a clinical recommendation was the
      factor most strongly associated with engaging in exercise/physical activity
      and/or controlling/losing weight. The most common reason for not exercising was a
      coexisting health condition/problem (22%), while the most common reason for not
      controlling/losing weight among those who were overweight/obese was that it was
      felt not to be necessary (51%). CONCLUSION: The provision of clinical
      recommendations from a health professional, providing advice on safe and suitable
      exercises/physical activities, as well as addressing misperceptions of the need
      to lose weight among the overweight/obese, may facilitate engagement in these
      health behaviors and ultimately reduce the consequences of arthritis.

PMID- 23861322
TI  - The pathobiology of collagens in glioma.
AB  - Malignant gliomas are characterized by a diffuse infiltration into the
      surrounding brain parenchyma. Infiltrating glioma cells exist in close proximity
      with components of the tumor microenvironment, including the extracellular matrix
      (ECM). Whereas levels of collagens in the normal adult brain are low, in glioma,
      collagen levels are elevated and play a vital role in driving tumor progression.
      This article provides a comprehensive overview of the nature of collagens found
      in gliomas and offers unique insight into the mechanisms by which cancer cells
      interact with this ECM via cellular factors such as integrins, discoidin domain
      receptors, and mannose receptors. Also discussed are the major remodeling
      pathways of brain tumor collagen, mediated primarily by matrix
      metalloproteinases, and the reciprocal relationship between these enzymes and the
      collagen receptors. Finally, a concluding perspective is offered on how the
      biophysical properties of the collagen ECM, in particular, mechanical stiffness
      and compliance, influence malignant outcome. A better understanding of the
      complex molecular interactions between glioma cells and the collagen ECM will
      provide new avenues to combat the rampant tumor progression and chemoresistance
      in brain cancer patients.

PMID- 23861324
TI  - Pelvic floor muscle training in women with stress urinary incontinence causes
      hypertrophy of the urethral sphincters and reduces bladder neck mobility during
      coughing.
AB  - AIMS: The purpose of this study was to determine the effect of a 12-week pelvic
      floor muscle (PFM) training program on urethral morphology and mobility in women
      with stress urinary incontinence (SUI). METHODS: Forty women with SUI were
      randomly assigned to one of two groups: the treatment group received 12 weekly
      physiotherapy sessions during which they learned how to properly contract their
      pelvic floor muscles (PFMs) and a home exercise program was prescribed, reviewed,
      and progressed; the control group received no treatment. Before and after the 12
      week study period, ultrasound imaging was used to evaluate bladder neck position
      and mobility during coughing and Valsalva maneuver in supine and in standing, as
      well as urethral morphology. Secondary outcome measures included a 3-day bladder
      diary, 30-min pad test, the Incontinence Impact Questionnaire (IIQ-7) and the
      Urogenital Distress Inventory (UDI-6). RESULTS: The women in the treatment group
      demonstrated reduced bladder neck mobility during coughing and increased cross
      sectional area of their urethra after as compared to before the training. These
      changes were not evident in the control group. No differences in the resting
      position of the bladder neck or in bladder neck excursion during Valsalva
      maneuver were noted in either group. Concomitantly the women in the treatment
      group demonstrated significant improvements in the 3-day bladder diary and IIQ-7
      after the PFM training and improved significantly more than the control group.
      CONCLUSION: Physiotherapist-supervised PFM training reduces bladder neck motion
      during coughing, and results in hypertrophy of the urethral sphincter in women
      who present with SUI.

PMID- 23861325
TI  - Glucose transporter 1 protein detected by enzyme-linked immunosorbent assay and
      immunocytochemistry: a useful diagnostic tool for malignant pleural effusions.
AB  - BACKGROUND: Glucose transporter 1 (GLUT1) is a hallmark of metabolic change in
      cancer cells. The objective of this study was to determine the role of GLUT1
      protein in diagnosing malignant pleural effusions by enzyme-linked immunosorbent
      assay (ELISA) and immunocytochemistry. METHODS: In total, 82 pleural effusions
      were collected and classified as benign (n = 42), atypical (n = 8), or malignant
      (n = 32) based on cytologic diagnosis and etiology. GLUT1 protein levels in
      effusions were measured by ELISA. GLUT1 expression also was determined by
      immunocytochemistry using cell blocks. RESULTS: GLUT1 levels were significantly
      higher in the malignant group compared with the benign group. Receiver operating
      characteristic curve analysis of benign and malignant pleural effusions for GLUT1
      yielded an area under the curve of 0.77, with a value of 1355.87 pg/dL as the
      optimal threshold for distinguishing benign from malignant effusions. With the
      ELISA method, the sensitivity, specificity, and accuracy were 78.1%, 69%, and
      73%, respectively. Malignant effusion cell blocks were positive for GLUT1
      expression in 84.4% of cases with 100% specificity and 93.2% accuracy. With the
      combination of high GLUT1 protein levels (>10,000 pg/dL) and immunocytochemistry
      to detect malignant pleural effusions, the sensitivity and accuracy increased to
      93.8% and 94.6%, respectively. The GLUT1 level measured by ELISA and the GLUT1
      expression detected by immunocytochemistry were positively correlated. In
      atypical effusions, 3 cases (37.5%) had GLUT1 levels higher than the cutoff
      value. CONCLUSIONS: The detection of GLUT1 protein by ELISA and
      immunocytochemistry may have utility in the diagnosis of malignant pleural
      effusions.

PMID- 23861326
TI  - An isotopically tagged azobenzene-based cleavable linker for quantitative
      proteomics.
AB  - Putting a number on it: Cleavable linkers are widely utilized in proteomics
      applications. In particular, the azobenzene-based linker cleaves under mild
      conditions that are mass-spectrometry-compatible. Here, we adapt this linker for
      quantitative proteomic applications by incorporating an isotopic label. These
      light- and heavy-tagged linkers enable the identification and quantitation of
      labeled peptides from multiple proteomes. 

PMID- 23861327
TI  - Wearing-off phenomena and levodopa-induced dyskinesias in posttraumatic
      hemiparkinsonism.

PMID- 23861328
TI  - Adherence to antihypertensive therapy prior to the first presentation of stroke
      in hypertensive adults: population-based study.
AB  - AIMS: Antihypertensive drug therapy is a major strategy of stroke prevention
      among hypertensive patients. The aim of this study was to estimate the excess
      risk of stroke associated with non-adherence to antihypertensive drug therapy
      among hypertensive patients. METHODS AND RESULTS: We conducted a population-based
      study using records from Finnish national registers for 1 January 1995 to 31
      December 2007. Of the 73 527 hypertensive patients aged 30 years or older and
      without pre-existing stroke or cardiovascular disease, 2144 died from stroke and
      24 560 were hospitalized due to stroke during the follow-up. At the 2- and 10
      year follow-up after the start of continuous antihypertensive medication, non
      adherent patients had 3.81 [95% confidence interval (CI) 2.85-5.10] and 3.01 (95%
      CI: 2.37-3.83) times higher odds of stroke death when compared with the adherent
      patients. The corresponding odds ratio (OR) for stroke hospitalization was 2.74
      (95% CI: 2.35-3.20) at Year 2 and 1.71 (95% CI: 1.49-1.96) at Year 10. In the
      stroke-event year, the ORs were higher, 5.68 (95% CI: 5.05-6.39) for stroke death
      and 1.87 (95% CI: 1.72-2.03) for hospitalization. Among those using agents acting
      on the renin-angiotensin system combined with diuretics or beta-blockers, these
      ORs were 7.49 (95% CI: 5.62-9.98) and 3.91 (95% CI: 3.23-4.75), respectively. The
      associations between non-adherence and stroke followed a dose-response pattern-
      the poorer the adherence, the greater the risk of death and hospitalization due
      to stroke. CONCLUSION: These data suggest that poor adherence to antihypertensive
      therapy substantially increases near- and long-term risk of stroke among
      hypertensive patients.

PMID- 23861329
TI  - Urodynamic effects of dutasteride add-on therapy to alpha-adrenergic antagonist
      for patients with benign prostatic enlargement: prospective pressure-flow study.
AB  - AIMS: We prospectively investigated the effect of dutasteride on clinical and
      urodynamic parameters in patients with benign prostatic enlargement (BPE).
      MATERIALS AND METHODS: A prospective study was conducted in consecutive 52
      patients with BPE who had not been satisfied with alpha-adrenergic antagonist
      monotherapy. Inclusion criteria were prostate volume (PV) >=30 ml and the
      International Prostate Symptom Score (IPSS) >=8 or QOL index >=3 under
      administration of an alpha-adrenergic antagonist without anticholinergic agent.
      Before and 24 weeks after dutasteride (0.5 mg daily) add-on treatment with
      preceding alpha-adrenergic antagonist, we assessed IPSS, uroflowmetry (UFM),
      filling cystometry, and pressure-flow study (PFS). RESULTS: Dutasteride add-on
      treatment significantly improved IPSS (from 18.4 +/- 7.5 to 13.8 +/- 7.3) and
      maximum flow rate (from 11.4 +/- 5.6 to 13.0 +/- 6.8 ml/sec). Maximum cystometric
      capacity on filling cystometry did not change significantly by dutasteride add-on
      treatment (221 +/- 97 and 240 +/- 104 ml before and after dutasteride add-on,
      respectively). All of the 41 patients with detrusor overactivity (DO) before
      dutasteride add-on treatment showed apparent reduction in the amplitude of
      involuntary detrusor contraction after dutasteride add-on treatment, including
      seven in whom DO disappeared. Dutasteride significantly reduced PV from 66.4 +/-
      31.9 to 47.6 +/- 26.1 ml. In PFS, detrusor pressure at maximum flow rate
      (PdetQmax) significantly decreased from 71.5 +/- 30.1 to 59.1 +/- 24.9 cmH2O
      after dutasteride add-on treatment. Bladder outlet obstruction index (BOOI) also
      decreased significantly from 55.2 +/- 31.9 to 42.3 +/- 27.9, and obstruction
      grade assessed by the Schafer nomogram significantly improved. CONCLUSIONS:
      Dutasteride can improve lower urinary tract symptoms by improving storage bladder
      function and relieving obstruction.

PMID- 23861330
TI  - Cytopathology fellowship outcomes assessment: milestones and evaluation
      toolboxes.

PMID- 23861331
TI  - A comparison of test statistics for the recovery of rapid growth-based
      enumeration tests.
AB  - This paper considers five test statistics for comparing the recovery of a rapid
      growth-based enumeration test with respect to the compendial microbiological
      method using a specific nonserial dilution experiment. The finite sample
      distributions of these test statistics are unknown, because they are functions of
      correlated count data. A simulation study is conducted to investigate the type I
      and type II error rates. For a balanced experimental design, the likelihood ratio
      test and the main effects analysis of variance (ANOVA) test for microbiological
      methods demonstrated nominal values for the type I error rate and provided the
      highest power compared with a test on weighted averages and two other ANOVA
      tests. The likelihood ratio test is preferred because it can also be used for
      unbalanced designs. It is demonstrated that an increase in power can only be
      achieved by an increase in the spiked number of organisms used in the experiment.
      The power is surprisingly not affected by the number of dilutions or the number
      of test samples. A real case study is provided to illustrate the theory.

PMID- 23861333
TI  - Editorial comment on: Boyle et al. Pelvic floor muscle training for prevention
      and treatment of urinary and fecal incontinence in antenatal and postnatal women:
      a short version Cochrane review. Neurourol Urodyn 2014;33:269-276.

PMID- 23861332
TI  - '...I've found once the weight had gone off, i've had a few twinges, but nothing
      like before'. Exploring weight and self-management of knee pain.
AB  - OBJECTIVES: Being overweight or obese is a key risk factor for the onset and
      exacerbation of knee pain. Policy and clinical guidelines encourage lifestyle
      changes as part of prevention or supported self-management. The present study
      explores how people who have not consulted for knee pain understand weight in
      relation to joint pain, if and how they self-manage and potential barriers to
      doing so. METHODS: A qualitative investigation was undertaken using repeat in
      depth semi-structured interviews and diary study. Thirteen participants who self
      reported moderate to severe pain and had not recently consulted their general
      practitioner for knee pain were recruited to the study. Thematic analysis of data
      was conducted. RESULTS: Participants did not recognize the association between
      being overweight and the onset of joint pain. The findings illuminate
      understandings of the effect of weight on joint pain, rationales and strategies
      for losing weight, and how participants' position responsibility for weight gain
      and loss. DISCUSSION: The present study suggests that clinicians need to account
      for existing understandings and actions of individuals in relation to weight and
      joint pain. Supported self-management and public health interventions need to be
      individually tailored accordingly.

PMID- 23861334
TI  - Comprehensive morphometry of subcortical grey matter structures in early-stage
      Parkinson's disease.
AB  - Previous imaging studies that investigated morphometric group differences of
      subcortical regions outside the substantia nigra between non-demented Parkinson's
      patients and controls either did not find any significant differences, or
      reported contradictory results. Here, we performed a comprehensive morphometric
      analysis of 20 cognitively normal, early-stage PD patients and 19 matched control
      subjects. In addition to relatively standard analyses of whole-brain grey matter
      volume and overall regional volumes, we examined subtle localized surface shape
      differences in striatal and limbic grey matter structures and tested their
      utility as a diagnostic marker. Voxel-based morphometry and volumetric
      comparisons did not reveal significant group differences. Shape analysis, on the
      other hand, demonstrated significant between-group shape differences for the
      right pallidum. Careful diffusion tractography analysis showed that the affected
      parts of the pallidum are connected subcortically with the subthalamic nucleus,
      the pedunculopontine nucleus, and the thalamus and cortically with the frontal
      lobe. Additionally, microstructural measurements along these pathways, but not
      along other pallidal connections, were significantly different between the two
      groups. Vertex-wise linear discriminant analysis, however, revealed limited
      accuracy of pallidal shape for the discrimination between patients and controls.
      We conclude that localized disease-related changes in the right pallidum in early
      Parkinson's disease, undetectable using standard voxel-based morphometry or
      volumetry, are evident using sensitive shape analysis. However, the subtle nature
      of these changes makes it unlikely that shape analysis alone will be useful for
      early diagnosis.

PMID- 23861335
TI  - Measurement of costs and scales for outcome evaluation in health economic studies
      of Parkinson's disease.
AB  - Health economic studies in Parkinson's disease (PD) have become increasingly
      common in recent years. Because several methodologies and instruments have been
      used to assess cost and outcomes in PD, the Movement Disorder Society (MDS)
      commissioned a Task Force to assess their properties and make recommendations
      regarding their use. A systematic literature review was conducted to explore the
      use of those instruments in PD and to determine which should be selected for this
      review. We assessed approaches to evaluate cost of illness (COI), cost
      effectiveness, and cost utilities, which include the use of direct (standard
      gamble, time trade-off. and visual analogue scales) and indirect instruments to
      measure health status and utilities. No validated instruments/models were
      identified for the evaluation of COI or cost-effectiveness in patients with PD;
      therefore, no instruments in this group are recommended. Among utility
      instruments, only a few of these outcome instruments have been used in the PD
      population, and only limited psychometric data are available for these
      instruments with respect to PD. Because psychometric data for further utility
      instruments in conditions other than PD already exist, the standard gamble and
      time trade-off methods and the EQ-5D (a European quality-of-life health states
      instrument) and Health Utility Index instruments met the criteria for scales that
      are "recommended (with limitations)," but only the EQ-5D has been assessed in
      detail in PD patients. The MDS Task Force recommends further study of these
      instruments in the PD population to establish core psychometric properties. For
      the assessment of COI, the Task Force considers the development of a COI
      instrument specifically for PD, like that available for Alzheimer's disease.

PMID- 23861336
TI  - Using the ASC:SIL ratio, human papillomavirus, and interobserver variability to
      assess and monitor cytopathology fellow training performance.
AB  - BACKGROUND: The goal of this study was to assess objective measurements of
      cytopathology fellow performance during their training. METHODS: The authors
      examined cytopathology performance characteristics (the ratio of atypical
      squamous cells to squamous intraepithelial lesions [ASC:SIL], interobserver
      variability [IOV], high-risk human papillomavirus [hr-HPV]-positive atypical
      squamous cells of undetermined significance [ASC-US]) of cytopathology fellows
      and assessed whether they could be used as tools to further their education.
      RESULTS: The ASC:SIL ratio, the proportion of hr-HPV-positive ASC-US, and IOV
      were calculated for 5 consecutive cytopathology fellows. The average ASC:SIL
      ratio for the fellows was 1.15. The overall average Cohen kappa-coefficient
      (kappa-value) between fellow and cytopathologist interpretation was 0.75
      (substantial agreement). The conditional kappa-value for ASC-US only was higher
      for cases the fellows called ASC-US (0.70) than for cases the cytopathologist
      called ASC-US (0.60). Of the cases that were diagnosed as "negative for
      intraepithelial lesion or malignancy" (NILM) by the fellow and ASC-US by the
      pathologist, 33.2% were positive for hr-HPV. This was higher than the expected
      frequency of hr-HPV-positive results in the NILM population, suggesting that the
      fellows were over-interpreting NILM in hr-HPV-positive cases that had cytologic
      features sufficient for an ASC-US interpretation. CONCLUSIONS: In this study,
      agreement was compared between trainee and cytopathologist to determine where a
      fellow's interpretation differed. With the use of IOV, the ASC:SIL ratio, and the
      percentage of hr-HPV-positive results in the NILM, ASC-US, and low-grade SIL
      categories, the authors attempted to outline objective assessments and areas of
      improvement for fellows before they enter independent practice.

PMID- 23861337
TI  - Oral administration of the flavonoid myricitrin prevents dextran sulfate sodium
      induced experimental colitis in mice through modulation of PI3K/Akt signaling
      pathway.
AB  - SCOPE: We investigated the protective effect of the flavonoid myricitrin in
      dextran sulfate sodium (DSS) induced colitis as promising candidate for the
      treatment of ulcerative colitis which is considered an important worldwide public
      health problem. METHODS AND RESULTS: Male CD1 mice were provided with a solution
      of filtered water containing 3% w/v DSS ad libitum over a 5-day period followed
      by 2 days with normal drinking water. Myricitrin was administered orally, once a
      day, at the doses 1, 3, and 10 mg/kg of body weight. At the end of day 7th, the
      animals were euthanized and the colonic tissue was collected to be analyzed by RT
      PCR, immunohistochemistry and Western blot. Our results showed that oral
      treatment with myricitrin exerts consistent anti-inflammatory action in DSS
      induced acute colitis in mice by the inhibition of the Akt/phosphatidylinositol-3
      kinase-dependent phosphorylation. Consequently, the phosphorylation of mitogen
      activated protein kinases (MAPK) p38, extracellular signal-regulated protein
      kinase (ERK1/2), and c-Jun N-terminal kinase and of the nuclear factor B (NF
      kappaB) was reduced and prevented an increase in the cytokines/chemokines levels.
      CONCLUSION: Together, these data reveal that the anti-inflammatory effect of
      myricitrin in DSS-induced colitis in mice is likely associated with its ability
      to prevent the activation of upstream kinases, such as phosphatidylinositol-3
      kinase-dependent Akt, NF-kappaB, and mitogen-activated protein kinase.

PMID- 23861338
TI  - Four fatalities involving 5-IT.
AB  - The new designer drug 5-(2-aminopropyl)indole (5-IT) is an indole derivative with
      stimulant properties. Its synthesis was first described by Albert Hofmann and
      Franz Troxler in 1962. We report four deaths associated with 5-IT and a validated
      high-performance liquid chromatography method for quantitation of the drug. In
      all four deaths, an autopsy was performed, and femoral venous blood, heart blood,
      urine and vitreous humor were submitted for toxicological analysis. The blood
      specimens were subjected to comprehensive testing that included alcohol analysis
      by headspace gas chromatography (GC-FID), acidic/neutral, basic drug and opiates
      screening by liquid chromatography-mass spectrometry (LC-MS-MS), and
      acidic/neutral, basic and acidic drugs screening by HPLC. In Case 1, a 25-year
      old male, 3,4-methylenedioxymethamphetamine (MDMA; <0.08 mg/L) and 5-IT
      (preserved femoral blood 1.2 mg/L; unpreserved femoral blood 0.8 mg/L; cardiac
      blood 1.2 mg/L; vitreous 0.8 mg/L and urine >10 mg/L) were detected, and death
      was attributed to the toxic effects of 5-IT. In Case 2, a 25-year-old female, 3,4
      methylenedioxy-N-methylcathinone (methylone, not quantitated), 6-(2
      aminopropyl)benzofuran (6-APB; femoral blood <0.08 mg/L) and 5-IT (preserved
      femoral blood 1.0 mg/L; unpreserved femoral blood 0.9 mg/L; cardiac blood 2.6
      mg/L; vitreous 1.4 mg/L and urine >10 mg/L) were detected, and death was
      attributed to the toxic 'cocktail effects' of the drugs. In Case 3, a 22-year-old
      male with a history of epilepsy, 5-IT (0.5 mg/L femoral blood) and 6-APB (0.2
      mg/L femoral blood) were detected, and death was attributed to the toxic effects
      of the drugs, with the role of epilepsy being indeterminate. In Case 4, a 25-year
      old female, 5-IT (0.4 mg/L femoral blood), amphetamine (0.4 mg/L femoral blood),
      MDMA (1.5 mg/L femoral blood), 4-methyl-N-ethylcathione, 3,4
      methylenedioxyamphetamine HCl (MDA), benzylpiperazine and 6-APB were detected,
      and death was attributed to the 'cocktail effect' of the drugs.

PMID- 23861339
TI  - Stability of 3,4-methylenedioxymethampetamine (MDMA), 4-methylmethcathinone
      (mephedrone) and 3-trifluromethylphenylpiperazine (3-TFMPP) in formalin solution.
AB  - Occasionally, the only postmortem samples available for analysis are contaminated
      with formaldehyde, either due to embalming prior to sampling or because analysis
      is carried out only when formalin-fixed tissues retained for histological study
      are available. Formaldehyde reacts with several drugs of forensic interest that
      contain either a primary or a secondary amine group to form their N-methyl
      derivatives. We investigated the stability of 3,4-methylenedioxymethampetamine
      (MDMA), 4-methylmethcathinone (mephedrone) and 3-trifluromethylphenylpiperazine
      (3-TFMPP) in formalin solutions using three different formaldehyde concentrations
      (5, 10 and 20%) and three different pHs (3.0, 7.0 and 9.5). Analysis was
      performed using high-performance liquid chromatography with diode array detection
      to determine the percentage degradation of each drug over time, up to 60 days.
      MDMA, mephedrone and 3-TFMPP are unstable in formalin solutions, with the
      degradation rate increasing with increasing pH. After 28 days in 20% formalin, pH
      9.5, there remained 57% of the initial 3-TFMPP concentration, 11% of the initial
      MDMA concentration and 4% of the initial mephedrone concentration. Forensic
      toxicologists should be aware that, when analyzing for these drugs in an embalmed
      body or in tissues stored in formalin solutions, the methylated form of the
      secondary amine-containing drug could be a more useful analyte than the parent
      drug.

PMID- 23861340
TI  - Diagnostic analysis of veterinary dried blood spots for toxic heavy metals
      exposure.
AB  - Dried blood spots (DBS) on filter paper have been used in human medicine since
      the 1960s, predominantly for screening in-borne metabolic disorders and more
      recently, for toxicology. Despite its 50-year existence, this technology has not
      been adopted by veterinarians for routine diagnoses and research. We have
      validated a novel DBS analytical procedure for the routine measurement of toxic
      heavy metals using 50 uL of whole blood on a single DBS by inductively coupled
      plasma mass spectrometry (ICP-MS). Targeted heavy metals are arsenic, cadmium,
      mercury, lead, selenium and thallium. The limits of quantitation (LOQ) on DBS
      are: arsenic 1.7 ug/L, cadmium 4.0 ug/L, mercury 13.7 ug/L, lead 13.3 ug/L,
      selenium 6.3 ug/L and thallium 1.5 ug/L. These LOQs suffice for routine diagnoses
      of heavy metal intoxication in domesticated and wildlife species as well as for
      basic, applied and epidemiological studies. The technique is ideal for population
      studies involving investigations of wildlife exposure to heavy metals and other
      environmental pollutants. The small blood volume involved (50 uL) makes it
      feasible to study small animals (birds, reptiles, amphibians and small mammals)
      that were previously excluded, or difficult to study due to the relatively large
      sample volumes required by current gold standard blood collection techniques.

PMID- 23861341
TI  - The effect of the 5-HT7 serotonin receptor agonist, LP44, on micturition in rats
      with chronic spinal cord injury.
AB  - AIMS: To better understand the effects of the selective 5-HT7 receptor agonist 4
      [2-(Methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1
      piperazinehexanamide hydrochloride (LP44) on micturition in spinal cord injury
      (SCI) rats. METHODS: Female Sprague-Dawley rats weighing 200-275 g were used. SCI
      was produced in 8 of the 16 rats by transection at the T10 level; cystometric
      study occurred 8-12 weeks post-transection. Intravesical pressure was monitored
      in urethane-anesthetized animals via a transvesical catheter. The selective 5-HT7
      antagonist (R)-3-[2-[2-(4-Methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]
      phenol hydrochloride (SB-269970) was administered after each LP44 dose-response
      curve (all drugs were administered intravenously, i.v). RESULTS: Compared to
      controls, SCI rats had a higher bladder capacity and residual volume, and a lower
      voiding efficiency. In SCI rats, LP44 (0.003-0.3 mg/kg, i.v) induced significant
      dose-dependent increases in micturition volume, significant dose-dependent
      decreases in residual volume, resulting in significant increases in voiding
      efficiency. CMG measurements showed a dose-dependent increase of the high
      frequency oscillation (HFO) activity, including the number of small oscillation
      per voiding. This was correlated with the improved voiding efficiency. SB-269970
      (0.1 mg/kg, i.v) partially or completely reversed all LP44-induced changes.
      CONCLUSIONS: HFOs seems to be correlated with external urethral sphincter (EUS)
      bursting activity during voiding. Both the bladder voiding efficiency and the
      periodic EUS activity were decreased in SCI rats. 5-HT7 receptor agonist can
      enhance HFO activity, thereby improving voiding efficiency. Whether or not these
      results may have implications for the future treatment of voiding dysfunction in
      SCI patients remains to be studied.

PMID- 23861342
TI  - Subthalamus deep brain stimulation for primary dystonia patients: a long-term
      follow-up study.
AB  - BACKGROUND: Deep brain stimulation has generated sustained improvement in motor
      function for patients with dystonia, but the long-term impact of subthalamic
      nucleus stimulation on dystonia has not been elucidated. METHODS: Patients with
      primary dystonia underwent bilateral subthalamic nucleus stimulation and were
      evaluated with the Burke-Fahn-Marsden dystonia rating scale and the Medical
      Outcomes Study 36-item Short-Form General Health Survey at baseline and 1 month,
      1 year, and 3 to 10 years postoperatively. RESULTS: Improvements in motor
      function according to the Burke-Fahn-Marsden dystonia rating scale at 1 month, 1
      year, and 3 to 10 years of stimulation were 55%, 77%, and 79%, respectively. The
      quality of life improved after 1 month of stimulation (P < 0.001), progressed
      within 1 year (P < 0.001), and then remained stable. Disease duration was
      negatively correlated with an improvement in motor function. CONCLUSIONS: Our
      results demonstrate that the subthalamus is an alternative to the globus pallidus
      internus as a target for deep brain stimulation to treat primary dystonia.

PMID- 23861343
TI  - Statistical improvements in functional magnetic resonance imaging analyses
      produced by censoring high-motion data points.
AB  - Subject motion degrades the quality of task functional magnetic resonance imaging
      (fMRI) data. Here, we test two classes of methods to counteract the effects of
      motion in task fMRI data: (1) a variety of motion regressions and (2) motion
      censoring ("motion scrubbing"). In motion regression, various regressors based on
      realignment estimates were included as nuisance regressors in general linear
      model (GLM) estimation. In motion censoring, volumes in which head motion
      exceeded a threshold were withheld from GLM estimation. The effects of each
      method were explored in several task fMRI data sets and compared using indicators
      of data quality and signal-to-noise ratio. Motion censoring decreased variance in
      parameter estimates within- and across-subjects, reduced residual error in GLM
      estimation, and increased the magnitude of statistical effects. Motion censoring
      performed better than all forms of motion regression and also performed well
      across a variety of parameter spaces, in GLMs with assumed or unassumed response
      shapes. We conclude that motion censoring improves the quality of task fMRI data
      and can be a valuable processing step in studies involving populations with even
      mild amounts of head movement.

PMID- 23861344
TI  - A facile method for preparation of tailored scaffolds for DNA-origami.
AB  - A convenient PCR cloning strategy allows one to prepare hundreds of picomoles of
      circular single-stranded DNA molecules, which are suitable as scaffolds for the
      assembly of DNA origami structures. The method is based on a combination of site
      directed mutagenesis and site- and ligation-independent cloning protocols, with
      simultaneous insertion of a nicking endonuclease restriction site on a double
      stranded plasmid of desired length and sequence. 

PMID- 23861345
TI  - BCL-2 hypermethylation is a potential biomarker of sensitivity to antimitotic
      chemotherapy in endocrine-resistant breast cancer.
AB  - Overexpression of the antiapoptotic factor BCL-2 is a frequent feature of
      malignant disease and is commonly associated with poor prognosis and resistance
      to conventional chemotherapy. In breast cancer, however, high BCL-2 expression is
      associated with favorable prognosis, estrogen receptor (ER) positivity, and low
      tumor grade, whereas low expression is included in several molecular signatures
      associated with resistance to endocrine therapy. In the present study, we
      correlate BCL-2 expression and DNA methylation profiles in human breast cancer
      and in multiple cell models of acquired endocrine resistance to determine whether
      BCL-2 hypermethylation could provide a useful biomarker of response to cytotoxic
      therapy. In human disease, diminished expression of BCL-2 was associated with
      hypermethylation of the second exon, in a region that overlapped a CpG island and
      an ER-binding site. Hypermethylation of this region, which occurred in 10% of
      primary tumors, provided a stronger predictor of patient survival (P = 0.019)
      when compared with gene expression (n = 522). In multiple cell models of acquired
      endocrine resistance, BCL-2 expression was significantly reduced in parallel with
      increased DNA methylation of the exon 2 region. The reduction of BCL-2 expression
      in endocrine-resistant cells lowered their apoptotic threshold to antimitotic
      agents: nocodazole, paclitaxel, and the PLK1 inhibitor BI2536. This phenomenon
      could be reversed with ectopic expression of BCL-2, and rescued with the BCL-2
      inhibitor ABT-737. Collectively, these data imply that BCL-2 hypermethylation
      provides a robust biomarker of response to current and next-generation cytotoxic
      agents in endocrine-resistant breast cancer, which may prove beneficial in
      directing therapeutic strategy for patients with nonresectable, metastatic
      disease.

PMID- 23861346
TI  - Inhibition of ABCB1 expression overcomes acquired docetaxel resistance in
      prostate cancer.
AB  - Docetaxel is the first-line standard treatment for castration-resistant prostate
      cancer. However, relapse eventually occurs due to the development of resistance
      to docetaxel. To unravel the mechanism of acquired docetaxel resistance, we
      established docetaxel-resistant prostate cancer cells, TaxR, from castration
      resistant C4-2B prostate cancer cells. The IC50 for docetaxel in TaxR cells was
      about 70-fold higher than parental C4-2B cells. Global gene expression analysis
      revealed alteration of expression of a total of 1,604 genes, with 52% being
      upregulated and 48% downregulated. ABCB1, which belongs to the ATP-binding
      cassette (ABC) transporter family, was identified among the top upregulated genes
      in TaxR cells. The role of ABCB1 in the development of docetaxel resistance was
      examined. Knockdown of ABCB1 expression by its specific shRNA or inhibitor
      resensitized docetaxel-resistant TaxR cells to docetaxel treatment by enhancing
      apoptotic cell death. Furthermore, we identified that apigenin, a natural product
      of the flavone family, inhibits ABCB1 expression and resensitizes docetaxel
      resistant prostate cancer cells to docetaxel treatment. Collectively, these
      results suggest that overexpression of ABCB1 mediates acquired docetaxel
      resistance and targeting ABCB1 expression could be a potential approach to
      resensitize docetaxel-resistant prostate cancer cells to docetaxel treatment.

PMID- 23861347
TI  - AZD3514: a small molecule that modulates androgen receptor signaling and function
      in vitro and in vivo.
AB  - Continued androgen receptor (AR) expression and signaling is a key driver in
      castration-resistant prostate cancer (CRPC) after classical androgen ablation
      therapies have failed, and therefore remains a target for the treatment of
      progressive disease. Here, we describe the biological characterization of
      AZD3514, an orally bioavailable drug that inhibits androgen-dependent and 
      independent AR signaling. AZD3514 modulates AR signaling through two distinct
      mechanisms, an inhibition of ligand-driven nuclear translocation of AR and a
      downregulation of receptor levels, both of which were observed in vitro and in
      vivo. AZD3514 inhibited testosterone-driven seminal vesicle development in
      juvenile male rats and the growth of androgen-dependent Dunning R3327H prostate
      tumors in adult rats. Furthermore, this class of compound showed antitumor
      activity in the HID28 mouse model of CRPC in vivo. AZD3514 is currently in phase
      I clinical evaluation.

PMID- 23861348
TI  - Midlife measurements of white matter microstructure predict subsequent regional
      white matter atrophy in healthy adults.
AB  - OBJECTIVES: Although age-related brain changes are becoming better understood,
      midlife patterns of change are still in need of characterization, and
      longitudinal studies are lacking. The aim of this study was to determine if
      baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI)
      predicts volume change over a 4-year interval. EXPERIMENTAL DESIGN: Forty-four
      cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1
      weighted magnetic resonance imaging. Tensor-based morphometry methods were used
      to evaluate volume change over time. FA values were extracted from regions of
      interest that included the cingulum, entorhinal white matter, and the genu and
      splenium of the corpus callosum. Baseline FA was used as a predictor variable,
      whereas gray and white matter atrophy rates as indexed by Tensor-based
      morphometry were the dependent variables. PRINCIPAL OBSERVATIONS: Over a 4-year
      period, participants showed significant contraction of white matter, especially
      in frontal, temporal, and cerebellar regions (P < 0.05, corrected for multiple
      comparisons). Baseline FA in entorhinal white matter, genu, and splenium was
      associated with longitudinal rates of atrophy in regions that included the
      superior longitudinal fasciculus, anterior corona radiata, temporal stem, and
      white matter of the inferior temporal gyrus (P < 0.001, uncorrected for multiple
      comparisons). CONCLUSIONS: Brain change with aging is characterized by extensive
      shrinkage of white matter. Baseline white matter microstructure as indexed by DTI
      was associated with some of the observed regional volume loss. The findings
      suggest that both white matter volume loss and microstructural alterations should
      be considered more prominently in models of aging and neurodegenerative diseases.

PMID- 23861349
TI  - Sensorimotor adaptation of speech in Parkinson's disease.
AB  - The basal ganglia are involved in establishing motor plans for a wide range of
      behaviors. Parkinson's disease (PD) is a manifestation of basal ganglia
      dysfunction associated with a deficit in sensorimotor integration and difficulty
      in acquiring new motor sequences, thereby affecting motor learning. Previous
      studies of sensorimotor integration and sensorimotor adaptation in PD have
      focused on limb movements using visual and force-field alterations. Here, we
      report the results from a sensorimotor adaptation experiment investigating the
      ability of PD patients to make speech motor adjustments to a constant and
      predictable auditory feedback manipulation. Participants produced speech while
      their auditory feedback was altered and maintained in a manner consistent with a
      change in tongue position. The degree of adaptation was associated with the
      severity of motor symptoms. The patients with PD exhibited adaptation to the
      induced sensory error; however, the degree of adaptation was reduced compared
      with healthy, age-matched control participants. The reduced capacity to adapt to
      a change in auditory feedback is consistent with reduced gain in the sensorimotor
      system for speech and with previous studies demonstrating limitations in the
      adaptation of limb movements after changes in visual feedback among patients with
      PD.

PMID- 23861351
TI  - Potential-dependent surface-enhanced resonance Raman spectroscopy at
      nanostructured TiO2 : a case study on cytochrome b5.
AB  - Nanostructured titanium dioxide (TiO2 ) electrodes, prepared by anodization of
      titanium, are employed to probe the electron-transfer process of cytochrome b5
      (cyt b5 ) by surface-enhanced resonance Raman (SERR) spectroscopy. Concomitant
      with the increased nanoscopic surface roughness of TiO2 , achieved by raising the
      anodization voltage from 10 to 20 V, the enhancement factor increases from 2.4 to
      8.6, which is rationalized by calculations of the electric field enhancement. Cyt
      b5 is immobilized on TiO2 under preservation of its native structure but it
      displays a non-ideal redox behavior due to the limited conductivity of the
      electrode material. The electron-transfer efficiency which depends on the
      crystalline phase of TiO2 has to be improved by appropriate doping for
      applications in bioelectrochemistry. 

PMID- 23861352
TI  - Mapping the moral maps: from alternate taxonomies to competing predictions.
AB  - The Model of Moral Motives will be of great value to moral psychology, both for
      its conceptualization of the provide/protect distinction at different levels of
      analysis (intrapersonal, interpersonal, intragroup, intergroup) and for its
      usefulness in integrating multiple theoretical perspectives on morality. To the
      latter end, this commentary makes three suggestions for improvements to the model
      and its integration with Moral Foundations Theory: (a) clarify what the columns
      of the model represent, (b) modify the one-to-one mapping of moral foundations
      onto the cells of the model, and (c) specify testable predictions uniquely
      generated by the model. Possibilities for future empirical tests of competing
      predictions are discussed, with the long-term aim of adjudicating between
      different theoretical accounts of ideological differences and the moral domain. 

PMID- 23861353
TI  - Moral context matters: a reply to Graham.
AB  - In response to Graham's comments, we attempt to clarify aspects of the Model of
      Moral Motives (MMM). The columns of our model represent three primary contexts
      for morality, involving behaviors focused on the self, another person, and one's
      group. The rows of MMM represent proscriptive morality and prescriptive morality,
      which broadly reflect motives to protect (from harm) and provide (help); these
      general motives have distinct manifestations depending on context (i.e., the
      columns of MMM). The article addresses misunderstandings in Graham's
      interpretation of MMM and includes discussions of criteria for categorizing
      prescriptive versus proscriptive moral motives, the central role of
      restrictiveness in proscriptive moral regulation, an inconsistency that provides
      support for the inclusion of group-based Social Justice, and further distinctions
      between Social Order and Social Justice informed by recent cross-cultural
      research. 

PMID- 23861354
TI  - Targeting the good target: an integrative review of the characteristics and
      consequences of being accurately perceived.
AB  - A person's judgeability, or the extent to which a person is easy to understand,
      plays an important role in how accurately a target will be perceived by others.
      Research on this topic, however, has not been systematic or well-integrated. The
      current review begins to remedy this by integrating the available research on
      judgeability from the fields of personality perception, nonverbal communication,
      and social cognition. Specifically, this review summarizes the characteristics
      that are likely to promote judgeability and explores its potential consequences.
      A diverse range of characteristics are identified as predictors of judgeability,
      all relating to three broader categories: psychological adjustment, social
      status, and socialization. Furthermore, being judgeable has a variety of
      potential, largely positive, consequences for the target, leaving good targets
      poised for greater personal and interpersonal well-being. Nevertheless, many
      questions on this topic remain and it is crucial for this relatively understudied
      topic to receive more systematic empirical attention. 

PMID- 23861355
TI  - Action, outcome, and value: a dual-system framework for morality.
AB  - Dual-system approaches to psychology explain the fundamental properties of human
      judgment, decision making, and behavior across diverse domains. Yet, the
      appropriate characterization of each system is a source of debate. For instance,
      a large body of research on moral psychology makes use of the contrast between
      "emotional" and "rational/cognitive" processes, yet even the chief proponents of
      this division recognize its shortcomings. Largely independently, research in the
      computational neurosciences has identified a broad division between two
      algorithms for learning and choice derived from formal models of reinforcement
      learning. One assigns value to actions intrinsically based on past experience,
      while another derives representations of value from an internally represented
      causal model of the world. This division between action- and outcome-based value
      representation provides an ideal framework for a dual-system theory in the moral
      domain. 

PMID- 23861356
TI  - Abnormalities of cortical thickness, subcortical shapes, and white matter
      integrity in subcortical vascular cognitive impairment.
AB  - Subcortical vascular cognitive impairment (sVCI) is caused by lacunar infarcts or
      extensive and/or diffuse lesions in the white matter that may disrupt the white
      matter circuitry connecting cortical and subcortical regions and result in the
      degeneration of neurons in these regions. This study used structural magnetic
      resonance imaging (MRI) and high angular resolution diffusion imaging (HARDI)
      techniques to examine cortical thickness, subcortical shapes, and white matter
      integrity in mild vascular cognitive impairment no dementia (VCIND Mild) and
      moderate-to-severe VCI (MSVCI). Our study found that compared to controls (n =
      25), VCIND Mild (n = 25), and MSVCI (n = 30) showed thinner cortex predominantly
      in the frontal cortex. The cortex in MSVCI was thinner in the parietal and
      lateral temporal cortices than that in VCIND Mild. Moreover, compared to
      controls, VCIND Mild and MSVCI showed smaller shapes (i.e., volume reduction) in
      the thalamus, putamen, and globus pallidus and ventricular enlargement. Finally,
      compared to controls, VCIND Mild, and MSVCI showed an increased mean diffusivity
      in the white matter, while decreased generalized fractional anisotropy was only
      found in the MSVCI subjects. The major axonal bundles involved in the white
      matter abnormalities were mainly toward the frontal regions, including the
      internal capsule/corona radiata, uncinate fasciculus, and anterior section of the
      inferior fronto-occipital fasciculus, and were anatomically connected to the
      affected cortical and subcortical structures. Our findings suggest that
      abnormalities in cortical, subcortical, and white matter morphology in sVCI occur
      in anatomically connected structures, and that abnormalities progress along a
      similar trajectory from the mild to moderate and severe conditions.

PMID- 23861357
TI  - Future refinement of methotrexate treatment in rheumatoid arthritis: comment on
      the article by Yazdany et al.

PMID- 23861358
TI  - Photonic crystal encoded microcarriers for biomaterial evaluation.
AB  - Photonic crystal encoded biomaterials microcarriers made from silica-hybrid
      photonic crystal beads are reported. The characteristic reflection peak
      originating from the physical periodic structure is used as the code of the
      microcarriers. They are stable during cell adhesion and culture on their surface.
      Based on this method, Different biomaterials are incorporated into different PCBs
      and used as encoded microcarriers for the multiplex evaluation of the interaction
      of cells and materials in a single culture experiment. These encoded
      microcarriers are ideal for multiplex bioevaluation of biomaterials or drug
      applications. 

PMID- 23861359
TI  - Treating patients with the best drugs.

PMID- 23861360
TI  - Reply to Parra-Ruiz.

PMID- 23861361
TI  - Case definitions, diagnostic algorithms, and priorities in encephalitis:
      consensus statement of the international encephalitis consortium.
AB  - BACKGROUND: Encephalitis continues to result in substantial morbidity and
      mortality worldwide. Advances in diagnosis and management have been limited, in
      part, by a lack of consensus on case definitions, standardized diagnostic
      approaches, and priorities for research. METHODS: In March 2012, the
      International Encephalitis Consortium, a committee begun in 2010 with members
      worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis
      and to set priorities for future study. RESULTS: We present a consensus document
      that proposes a standardized case definition and diagnostic guidelines for
      evaluation of adults and children with suspected encephalitis. In addition, areas
      of research priority, including host genetics and selected emerging infections,
      are discussed. CONCLUSIONS: We anticipate that this document, representing a
      synthesis of our discussions and supported by literature, will serve as a
      practical aid to clinicians evaluating patients with suspected encephalitis and
      will identify key areas and approaches to advance our knowledge of encephalitis.

PMID- 23861362
TI  - Interpreting secondary cardiac disease variants in an exome cohort.
AB  - BACKGROUND: Massively parallel sequencing to identify rare variants is widely
      practiced in medical research and in the clinic. Genome and exome sequencing can
      identify the genetic cause of a disease (primary results), but it can also
      identify pathogenic variants underlying diseases that are not being sought
      (secondary or incidental results). A major controversy has developed surrounding
      the return of secondary results to research participants. We have piloted a
      method to analyze exomes to identify participants at risk for cardiac
      arrhythmias, cardiomyopathies, or sudden death. METHODS AND RESULTS: Exome
      sequencing was performed on 870 participants not selected for arrhythmia,
      cardiomyopathy, or a family history of sudden death. Exome data from 22 cardiac
      arrhythmia- and 41 cardiomyopathy-associated genes were analyzed using an
      algorithm that filtered results on genotype quality, frequency, and database
      information. We identified 1367 variants in the cardiomyopathy genes and 360
      variants in the arrhythmia genes. Six participants had pathogenic variants
      associated with dilated cardiomyopathy (n=1), hypertrophic cardiomyopathy (n=2),
      left ventricular noncompaction (n=1), or long-QT syndrome (n=2). Two of these
      participants had evidence of cardiomyopathy and 1 had left ventricular
      noncompaction on echocardiogram. Three participants with likely pathogenic
      variants had prolonged QTc. Family history included unexplained sudden death
      among relatives. CONCLUSIONS: Approximately 0.5% of participants in this study
      had pathogenic variants in known cardiomyopathy or arrhythmia genes. This high
      frequency may be due to self-selection, false positives, or underestimation of
      the prevalence of these conditions. We conclude that clinically important
      cardiomyopathy and dysrhythmia secondary variants can be identified in unselected
      exomes.

PMID- 23861363
TI  - Whole exome sequencing identifies a causal RBM20 mutation in a large pedigree
      with familial dilated cardiomyopathy.
AB  - BACKGROUND: Whole exome sequencing is a powerful technique for Mendelian disease
      gene discovery. However, variant prioritization remains a challenge. We applied
      whole exome sequencing to identify the causal variant in a large family with
      familial dilated cardiomyopathy of unknown pathogenesis. METHODS AND RESULTS: A
      large family with autosomal dominant, familial dilated cardiomyopathy was
      identified. Exome capture and sequencing were performed in 3 remotely related,
      affected subjects predicted to share <0.1% of their genomes by descent. Shared
      variants were filtered for rarity, evolutionary conservation, and predicted
      functional significance, and remaining variants were filtered against 71 locally
      generated exomes. Variants were also prioritized using the Variant Annotation
      Analysis and Search Tool. Final candidates were validated by Sanger sequencing
      and tested for segregation. There were 664 shared heterozygous nonsense,
      missense, or splice site variants, of which 26 were rare (minor allele frequency
      <=0.001 or not reported) in 2 public databases. Filtering against internal exomes
      reduced the number of candidates to 2, and of these, a single variant (c.1907
      G>A) in RBM20, segregated with disease status and was absent in unaffected
      internal reference exomes. Bioinformatic prioritization with Variant Annotation
      Analysis and Search Tool supported this result. CONCLUSIONS: Whole exome
      sequencing of remotely related dilated cardiomyopathy subjects from a large,
      multiplex family, followed by systematic filtering, identified a causal RBM20
      mutation without the need for linkage analysis.

PMID- 23861365
TI  - "Occam's razor" and identical twins with discordant Parkinson's Disease.

PMID- 23861364
TI  - Do genetic modifiers of high-density lipoprotein cholesterol and triglyceride
      levels also modify their response to a lifestyle intervention in the setting of
      obesity and type-2 diabetes mellitus?: The Action for Health in Diabetes (Look
      AHEAD) study.
AB  - BACKGROUND: High-density lipoprotein cholesterol (HDL-C) and triglycerides are
      cardiovascular risk factors susceptible to lifestyle behavior modification and
      genetics. We hypothesized that genetic variants identified by genome-wide
      association studies as associated with HDL-C or triglyceride levels modify 1-year
      treatment response to an intensive lifestyle intervention, relative to a usual
      care of diabetes mellitus support and education. METHODS AND RESULTS: We
      evaluated 82 single-nucleotide polymorphisms, which represent 31 loci
      demonstrated by genome-wide association studies to be associated with HDL-C and
      triglycerides, in 3561 participants who consented for genetic studies and met
      eligibility criteria. Variants associated with higher baseline HDL-C levels,
      cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC)
      rs8034802, were found to be associated with HDL-C increases with intensive
      lifestyle intervention (P=0.0038 and 0.013, respectively) and had nominally
      significant treatment interactions (P=0.047 and 0.046, respectively). The fatty
      acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (P=0.017),
      was associated with HDL-C increases with intensive lifestyle intervention
      (0.0037) and had a nominal treatment interaction (P=0.035). Apolipoprotein B
      (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally
      significant associations with HDL-C and triglyceride changes with intensive
      lifestyle intervention and a treatment interaction (P<0.05).
      Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms
      (rs4082919) showed the most significant triglyceride treatment interaction in the
      full cohort (P=0.0009). CONCLUSIONS: This is the first study to identify genetic
      variants modifying lipid responses to a randomized lifestyle behavior
      intervention in overweight or obese individuals with diabetes mellitus. The
      effects of genetic factors on lipid changes may differ from the effects on
      baseline lipids and are modifiable by behavioral intervention.

PMID- 23861366
TI  - Acute complications of movement disorders surgery: effects of age and
      comorbidities.
AB  - The most common indication for movement disorder surgery is Parkinson's disease
      (PD), and the incidence of PD increases with age. The analysis reported here was
      undertaken with the primary goal of examining whether there is a relationship
      between peri-operative complications and age. The Nationwide Inpatient Sample
      (Agency for Healthcare Research and Quality, Rockville, MD, USA) was queried for
      10 years beginning in 1999 for patients undergoing deep brain stimulator
      insertion, pallidotomy, and thalamotomy for treatment of PD, essential tremor,
      and dystonia. Inpatient complications, including death, stroke (both ischemic and
      hemorrhagic), and other overall complications were examined. The relative risks
      associated with advanced age; primary diagnosis; treatment modality; the
      diagnoses of hypertension, diabetes, and nicotinism; and the cumulative number of
      comorbidities were examined. There were 5464 patients who met inclusion criteria,
      including 4145 patients treated for PD and 4961 patients treated with deep brain
      stimulation (DBS). Overall in-hospital mortality was 0.26%, with 0.15% related to
      surgical factors. There was a correlation between in-hospital mortality,
      increasing age, and number of medical comorbidities. After multivariate
      regression no factor remained predictive of mortality. Having more than 1 medical
      comorbidity or PD increased the risk of in-hospital complications. Patients with
      PD were more likely to suffer hemorrhage or stroke. Hypertension, diabetes,
      nicotinism, and modality of treatment were not associated with increased
      mortality, hemorrhage or stroke risk, or in-hospital mortality in univariate or
      multivariate analysis. Both age and medical comorbidity are correlated with in
      hospital complications, but age appears to serve as a surrogate for comorbidity.
      Surgery for PD appears to carry an increased risk of hemorrhage or stroke and in
      hospital complications.

PMID- 23861367
TI  - Patterns of atypical antipsychotic therapy use in adults with bipolar I disorder
      in the USA.
AB  - OBJECTIVES: This study aims to describe the utilization patterns of atypical
      antipsychotics (AA) among insured patients with bipolar I disorder in the USA.
      METHODS: We studied patients with bipolar I disorder who newly initiated an oral
      AA between 2002 and 2008. Utilization measures included adherence [medication
      possession ratio (MPR) >=80%], persistence (gaps <=15 days between refills and an
      absence of >=30 days of continuous concomitant non-index AA use), non-compliance
      (16-29 day gaps with no evidence of switch/augmentation), and discontinuation of
      the index AA (>=30 days without index AA, no evidence of switch/augmentation).
      RESULTS: The study included 16 807 patients: mean age 43.3 years, 67.7% female.
      Overall, adherence to the index AA was low (8.3%; mean MPR = 0.2). Only 10.5% of
      the patients were persistent to index AA, another 13.6% were non-compliant, and
      63.4% discontinued index AA with an average time to discontinuation of 66 days. A
      majority (69.5%) of the discontinued patients did not resume any antipsychotic
      therapy. Results were similar across insurance types and index AA. CONCLUSION:
      Adherence to and persistence with AA treatment were low in new users with bipolar
      I disorder. Most patients discontinued the index AA and did not restart any
      antipsychotic treatment. Future study should distinguish physician-directed
      discontinuation versus patient non-adherence.

PMID- 23861368
TI  - Hexarelin treatment in male ghrelin knockout mice after myocardial infarction.
AB  - Both ghrelin and the synthetic analog hexarelin are reported to possess
      cardioprotective actions that are mainly exerted through different receptors.
      However, their effects on acute myocardial infarction have not been compared in
      vivo. This study aimed to clarify whether hexarelin treatment can compensate for
      ghrelin deficiency in ghrelin-knockout mice and to compare the effects of
      hexarelin (400 nmol/kg/d, sc) and equimolar ghrelin treatment after myocardial
      infarction. Myocardial infarction was produced by left coronary artery ligation
      in male ghrelin-knockout mice, which then received ghrelin, hexarelin, or vehicle
      treatment for 2 weeks. The mortality within 2 weeks was significantly lower in
      the hexarelin group (6.7%) and ghrelin group (14.3%) than in the vehicle group
      (50%) (P < .05). A comparison of cardiac function 2 weeks after infarction showed
      that in the ghrelin and hexarelin treatment groups, cardiac output was greater,
      whereas systolic function, represented by ejection fraction, and diastolic
      function, represented by dP/dt min (peak rate of pressure decline), were
      significantly superior compared with the vehicle group (P < .05). Hexarelin
      treatment was more effective than ghrelin treatment, as indicated by the ejection
      fraction, dP/dt max (peak rate of pressure rise), and dP/dt min. Telemetry
      recording and heart rate variability analysis demonstrated that sympathetic
      nervous activity was clearly suppressed in the hexarelin and ghrelin groups
      relative to the vehicle group. Our data demonstrated that hexarelin treatment can
      result in better heart function than ghrelin treatment 2 weeks after myocardial
      infarction in ghrelin-knockout mice, although both hormones have similar effects
      on heart rate variability and mortality. 

PMID- 23861369
TI  - A novel experimental strategy to assess the metabolic effects of selective
      activation of a G(q)-coupled receptor in hepatocytes in vivo.
AB  - Increased hepatic glucose production is a key pathophysiological feature of type
      2 diabetes. Like all other cell types, hepatocytes express many G protein-coupled
      receptors (GPCRs) that are linked to different functional classes of
      heterotrimeric G proteins. The important physiological functions mediated by G(s)
      coupled hepatic glucagon receptors are well-documented. In contrast, little is
      known about the in vivo physiological roles of hepatocyte GPCRs that are linked
      to G proteins of the G(q) family. To address this issue, we established a
      transgenic mouse line (Hep-Rq mice) that expressed a G(q)-linked designer
      receptor (Rq) in a hepatocyte-selective fashion. Importantly, Rq could no longer
      bind endogenous ligands but could be selectively activated by a synthetic drug,
      clozapine-N-oxide. Clozapine-N-oxide treatment of Hep-Rq mice enabled us to
      determine the metabolic consequences caused by selective activation of a G(q)
      coupled GPCR in hepatocytes in vivo. We found that acute Rq activation in vivo
      led to pronounced increases in blood glucose levels, resulting from increased
      rates of glycogen breakdown and gluconeogenesis. We also demonstrated that the
      expression of the V(1b) vasopressin receptor, a G(q)-coupled receptor expressed
      by hepatocytes, was drastically increased in livers of ob/ob mice, a mouse model
      of diabetes. Strikingly, treatment of ob/ob mice with a selective V(1b) receptor
      antagonist led to reduced glucose excursions in a pyruvate challenge test. Taken
      together, these findings underscore the importance of G(q)-coupled receptors in
      regulating hepatic glucose fluxes and suggest novel receptor targets for the
      treatment of type 2 diabetes.

PMID- 23861370
TI  - Autocrine and paracrine mechanisms of prostaglandin E2 action on
      trophoblast/conceptus cells through the prostaglandin E2 receptor (PTGER2) during
      implantation.
AB  - The conceptus and endometrium secrete large amounts of prostaglandin E2 (PGE2)
      into the porcine uterine lumen during the periimplantation period. We
      hypothesized that PGE2 acts on conceptus/trophoblast cells through auto- and
      paracrine mechanisms. Real-time RT-PCR analysis revealed that PGE2 receptor
      (PTGER)2 mRNA was 14-fold greater in conceptuses/trophoblasts on days 14-25
      (implantation and early placentation period) vs preimplantation day 10-13
      conceptuses (P < .05). Similarly, expression of PTGER2 protein increased during
      implantation. Conceptus expression of PTGER4 mRNA and protein did not differ on
      days 10-19. PGE2 stimulated PTGER2 mRNA expression in day 15 trophoblast cells
      through PTGER2 receptor signaling. PGE2 elevated aromatase expression and
      estradiol-17beta secretion by trophoblast cells. Moreover, PGE2 and the PTGER2
      agonist, butaprost, increased the adhesive capacity of both human HTR-8/SVneo
      trophoblast and primary porcine trophoblast cells to extracellular matrix. This
      PGE2-induced alteration in trophoblast cell adhesion to extracellular matrix was
      abolished by incubation of these cells with AH6809 (PTGER2 antagonist), ITGAVB3
      directed tetrapeptide arg-gly-asp-ser or integrin ITGAVB3 antibody. PGE2
      stimulated adhesion of porcine trophoblast cells via the estrogen receptor and
      MEK/MAPK signaling pathway. PGE2 induced phosphorylation of MAPK1/MAPK3 through
      PTGER2 and up-regulated expression of cell adhesion proteins such as focal
      adhesion kinase and intercellular adhesion molecule-1. Our study indicates that
      elevated PGE2 in the periimplantation uterine lumen stimulates conceptus PTGER2
      expression, which in turn promotes trophoblast adhesion via integrins, and
      synthesis and secretion of the porcine embryonic signal estradiol-17beta.
      Moreover, the mechanism through which PGE2 increases trophoblast adhesion is not
      species specific because it is PTGER2- and integrin-dependent in both porcine and
      human trophoblast cells.

PMID- 23861371
TI  - The hepatic orosomucoid/alpha1-acid glycoprotein gene cluster is regulated by the
      nuclear bile acid receptor FXR.
AB  - The alpha-1-acid glycoprotein/orosomucoids (ORMs) are members of the lipocalin
      protein family. Encoded by 3 polymorphic genes in mouse (2 in man, 1 in rat),
      ORMs are expressed in hepatocytes and function as acute-phase proteins secreted
      in plasma under stressful conditions. In addition to their role of nanocarrier,
      ORMs are involved in several pathophysiological processes such as
      immunosuppression, cardioprotection, and inflammatory bowel disease. The nuclear
      bile acid receptor farnesoid X receptor (FXR) regulates bile acid homeostasis and
      lipid and glucose metabolism and is an important modulator of enterohepatic
      functions. Here we report that hepatic FXR deletion in mice affects the
      expression of several members of the lipocalin family, among which ORMs are
      identified as direct FXR target genes. Indeed, a FXR response element upstream of
      the mouse Orm1 promoter was identified to which hepatic, but not ileal, FXR can
      bind and activate ORM expression in vitro and in vivo. However, ORMs are
      regulated in a species-specific manner because the ORM cluster is regulated by
      FXR neither in human nor rat cell lines. Consistent with these data, chromatin
      immunoprecipitation sequencing analysis of the FXR genomic binding sites did not
      detect any FXR response element in the vicinity of the human or rat ORM gene
      cluster. Thus, bile acids and their cognate nuclear receptor, FXR, are regulators
      of ORM expression, with potential implications for the species-specific metabolic
      and inflammation control by FXR because the expression of the proinflammatory
      genes in epididymal white adipose tissue was dependent on liver FXR activation. 

PMID- 23861373
TI  - Dim light at night exaggerates weight gain and inflammation associated with a
      high-fat diet in male mice.
AB  - Elevated nighttime light exposure is associated with symptoms of metabolic
      syndrome. In industrialized societies, high-fat diet (HFD) and exposure to light
      at night (LAN) often cooccur and may contribute to the increasing obesity
      epidemic. Thus, we hypothesized that dim LAN (dLAN) would provoke additional and
      sustained body mass gain in mice on a HFD. Male mice were housed in either a
      standard light/dark cycle or dLAN and fed either chow or HFD. Exposure to dLAN
      and HFD increase weight gain, reduce glucose tolerance, and alter insulin
      secretion as compared with light/dark cycle and chow, respectively. The effects
      of dLAN and HFD appear additive, because mice exposed to dLAN that were fed HFD
      display the greatest increases in body mass. Exposure to both dLAN and HFD also
      change the timing of food intake and increase TNFalpha and MAC1 gene expression
      in white adipose tissue after 4 experimental weeks. Changes in MAC1 gene
      expression occur more rapidly due to HFD as compared with dLAN; after 5 days of
      experimental conditions, mice fed HFD already increase MAC1 gene expression in
      white adipose tissue. HFD also elevates microglia activation in the arcuate
      nucleus of the hypothalamus and hypothalamic TNFalpha, IL-6, and Ikbkb gene
      expression. Microglia activation is increased by dLAN, but only among chow-fed
      mice and dLAN does not affect inflammatory gene expression. These results suggest
      that dLAN exaggerates weight gain and peripheral inflammation associated with
      HFD. 

PMID- 23861372
TI  - Precocious puberty and Leydig cell hyperplasia in male mice with a gain of
      function mutation in the LH receptor gene.
AB  - The LH receptor (LHR) is critical for steroidogenesis and gametogenesis. Its
      essential role is underscored by the developmental and reproductive abnormalities
      that occur due to genetic mutations identified in the human LHR. In males,
      activating mutations are associated with precocious puberty and Leydig cell
      hyperplasia. To generate a mouse model for the human disease, we have introduced
      an aspartic acid to glycine mutation in amino acid residue 582 (D582G) of the
      mouse LHR gene corresponding to the most common D578G mutation found in boys with
      familial male-limited precocious puberty (FMPP). In transfected cells, mouse
      D582G mLHR exhibited constitutive activity with a 23-fold increase in basal cAMP
      levels compared with the wild-type receptor. A temporal study of male mice from 7
      days to 24 weeks indicated that the knock-in mice with the mutated receptor
      (KiLHR(D582G)) exhibited precocious puberty with elevated testosterone levels as
      early as 7 days of age and through adulthood. Leydig cell-specific genes encoding
      LHR and several steroidogenic enzymes were up-regulated in KiLHR(D582G) testis.
      Leydig cell hyperplasia was detected at all ages, whereas Sertoli and germ cell
      development appeared normal. A novel finding from our studies, not previously
      reported in the FMPP cases, is that extensive hyperplasia is commonly found
      around the periphery of the testis. We further demonstrate that the hyperplasia
      is due to premature proliferation and precocious differentiation of adult Leydig
      cells in the KiLHR(D582G) testis. The KiLHR(D582G) mice provide a mouse model for
      FMPP, and we suggest that it is a useful model for studying pathologies
      associated with altered LHR signaling. 

PMID- 23861376
TI  - The orexigenic effect of orexin-A revisited: dependence of an intact growth
      hormone axis.
AB  - Fifteen years ago orexins were identified as central regulators of energy
      homeostasis. Since then, that concept has evolved considerably and orexins are
      currently considered, besides orexigenic neuropeptides, key modulators of sleep
      wake cycle and neuroendocrine function. Little is known, however, about the
      effect of the neuroendocrine milieu on orexins' effects on energy balance. We
      therefore investigated whether hypothalamic-pituitary axes have a role in the
      central orexigenic action of orexin A (OX-A) by centrally injecting
      hypophysectomized, adrenalectomized, gonadectomized (male and female),
      hypothyroid, and GH-deficient dwarf rats with OX-A. Our data showed that the
      orexigenic effect of OX-A is fully maintained in adrenalectomized and
      gonadectomized (females and males) rats, slightly reduced in hypothyroid rats,
      and totally abolished in hypophysectomized and dwarf rats when compared with
      their respective vehicle-treated controls. Of note, loss of the OX-A effect on
      feeding was associated with a blunted OX-A-induced increase in the expression of
      either neuropeptide Y or its putative regulator, the transcription factor cAMP
      response-element binding protein, as well as its phosphorylated form, in the
      arcuate nucleus of the hypothalamus of hypophysectomized and dwarf rats. Overall,
      this evidence suggests that the orexigenic action of OX-A depends on an intact GH
      axis and that this neuroendocrine feedback loop may be of interest in the
      understanding of orexins action on energy balance and GH deficiency. 

PMID- 23861375
TI  - High-fat intake during pregnancy and lactation exacerbates high-fat diet-induced
      complications in male offspring in mice.
AB  - Altered fetal environments, such as a high-fat milieu, induce metabolic
      abnormalities in offspring. Different postnatal environments reveal the
      predisposition for adult diseases that occur during the fetal period. This study
      investigates the ability of a maternal high-fat diet (HFD) to program metabolic
      responses to HFD reexposure in offspring after consuming normal chow for 23 weeks
      after weaning. Wild-type CD1 females were fed a HFD (H) or control (C) chow
      during pregnancy and lactation. At 26 weeks of age, offspring were either
      reexposed (H-C-H) or newly exposed (C-C-H) to the HFD for 19 weeks. Body weight
      was measured weekly, and glucose and insulin tolerance were measured after 10 and
      18 weeks on the HFD. The metabolic profile of offspring on a HFD or C diet during
      pregnancy and lactation and weaned onto a low-fat diet was similar at 26 weeks. H
      C-H offspring gained more weight and developed larger adipocytes after being
      reintroduced to the HFD later in life than C-C-H. H-C-H mice were glucose and
      insulin intolerant and showed reduced gene expression of cox6a2 and atp5i in
      muscle, indicating mitochondrial dysfunction. In adipocytes, the expression of
      slc2a4, srebf1, and adipoq genes was decreased in H-C-H mice compared with C-C-C,
      indicating insulin resistance. H-C-H showed extensive hepatosteatosis,
      accompanied by increased gene expression for cd36 and serpin1, compared with C-C
      H. Perinatal exposure to a HFD programs a more deleterious response to a HFD
      challenge later in life even after an interval of normal diet in mice. 

PMID- 23861374
TI  - Cardiac expression of human type 2 iodothyronine deiodinase increases glucose
      metabolism and protects against doxorubicin-induced cardiac dysfunction in male
      mice.
AB  - Altered glucose metabolism in the heart is an important characteristic of
      cardiovascular and metabolic disease. Because thyroid hormones have major effects
      on peripheral metabolism, we examined the metabolic effects of heart-selective
      increase in T3 using transgenic mice expressing human type 2 iodothyronine
      deiodinase (D2) under the control of the alpha-myosin heavy chain promoter (MHC
      D2). Hyperinsulinemic-euglycemic clamps showed normal whole-body glucose disposal
      but increased hepatic insulin action in MHC-D2 mice as compared to wild-type (WT)
      littermates. Insulin-stimulated glucose uptake in heart was not altered, but
      basal myocardial glucose metabolism was increased by more than two-fold in MHC-D2
      mice. Myocardial lipid levels were also elevated in MHC-D2 mice, suggesting an
      overall up-regulation of cardiac metabolism in these mice. The effects of
      doxorubicin (DOX) treatment on cardiac function and structure were examined using
      M-mode echocardiography. DOX treatment caused a significant reduction in
      ventricular fractional shortening and resulted in more than 50% death in WT mice.
      In contrast, MHC-D2 mice showed increased survival rate after DOX treatment, and
      this was associated with a six-fold increase in myocardial glucose metabolism and
      improved cardiac function. Myocardial activity and expression of AMPK, GLUT1, and
      Akt were also elevated in MHC-D2 and WT mice following DOX treatment. Thus, our
      findings indicate an important role of thyroid hormone in cardiac metabolism and
      further suggest a protective role of glucose utilization in DOX-mediated cardiac
      dysfunction. 

PMID- 23861377
TI  - Deletion of growth hormone receptors in postnatal skeletal muscle of male mice
      does not alter muscle mass and response to pathological injury.
AB  - In this study, we investigated whether loss of GH receptor (GHR) signaling in
      postnatal skeletal muscle alters muscle mass and regenerative ability in adult
      mice and whether this was dependent on IGF-1 receptor (IGF-1R) signaling. To do
      so, we used mouse models with skeletal muscle-specific loss of GHR signaling
      (mGHRKO), IGF-1R and insulin receptor signaling (MKR), or both GHR and IGF
      1R/insulin receptor signaling (mGHRKO/MKR). We did not find a reduction in muscle
      cross-sectional area, fiber type composition, or response to pathological muscle
      injury in male mGHRKO and mGHRKO/MKR mice when compared with control and MKR
      mice, respectively. This could potentially be explained by unchanged skeletal
      muscle Igf-1 expression in mGHRKO and mGHRKO/MKR mice relative to control and MKR
      mice, respectively. Furthermore, MKR and mGHRKO/MKR mice, but not mGHRKO mice,
      demonstrated reduced fiber fusion after cardiotoxin injection, suggesting that
      IGF-1, and not GH, promotes fiber fusion in adult mice. In summary, our data
      suggest that GHR signaling in postnatal skeletal muscle does not play a
      significant role in regulating muscle mass or muscle regeneration. Additionally,
      in our model, muscle Igf-1 expression is not dependent on GHR signaling in
      postnatal skeletal muscle. 

PMID- 23861378
TI  - Neural growth hormone implicated in body weight sex differences.
AB  - As for many human diseases, the incidence of obesity and its associated health
      risks are sexually dimorphic: worldwide the rate of obesity is higher in women.
      Sex differences in metabolism, appetite, body composition, and fat deposition are
      contributing biological factors. Gonadal hormones regulate the development of
      many sexually dimorphic traits in humans and animals, and, in addition, studies
      in mice indicate a role for direct genetic effects of sex chromosome dosage on
      body weight, deposition of fat, and circadian timing of feeding behavior.
      Specifically, mice of either sex with 2 X chromosomes, typical of normal females,
      have heavier body weights, gain more weight, and eat more food during the light
      portion of the day than mice of either sex with a single X chromosome. Here we
      test the effects of X chromosome dosage on body weight and report that gonadal
      females with 2 X chromosomes express higher levels of GH gene (Gh) mRNA in the
      preoptic area (POA) of the hypothalamus than females with 1 X chromosome and
      males. Furthermore, Gh expression in the POA of the hypothalamus of mice with 2 X
      chromosomes correlated with body weight; GH is known to have orexigenic
      properties. Acute infusion of GH into the POA increased immediate food intake in
      normal (XY) males. We propose that X inactivation-escaping genes modulate Gh
      expression and food intake, and this is part of the mechanism by which
      individuals with 2 X chromosomes are heavier than individuals with a single X
      chromosome. 

PMID- 23861379
TI  - TGF-beta induces Wnt10b in osteoclasts from female mice to enhance coupling to
      osteoblasts.
AB  - In young adults, bone lost through osteoclast-mediated resorption is precisely
      replaced in both location and amount. Understanding how these two processes are
      coupled is crucial to advancing treatments for osteoporosis, a disease that
      progresses when the processes become uncoupled. We documented that osteoclasts
      secrete the mammalian integration 1 gene that is the homolog of Drosophila
      Wngless (Wnt) 10b, bone morphogenetic protein 6 (BMP6), and the chemokine
      sphingosin 1 phosphate (S1P) to promote mesenchymal cell mineralization in vitro.
      During bone resorption, TGF-beta1 is released from the bone extracellular matrix
      and activated by osteoclasts. Thus, TGF-beta1 levels are elevated during the
      resorption phase of bone turnover. We therefore investigated the influences of
      TGF-beta1 on osteoclast-mediated support of mineralization. TGF-beta1 increased
      osteoclast production of Wnt10b, but not BMP6 or S1P. Blocking Wnt10b activity
      with the Wnt signaling inhibitor Dickkoph-related protein 1 suppressed the
      ability of TGF-beta-treated osteoclast-conditioned media to promote osteoblast
      mineralization. Examination of TGF-beta signaling in osteoclasts revealed that
      induction of Wnt10b expression was dependent on Smad2/3 activation and
      independent from TGF-beta1 stimulation of protein kinase B (AKT) or MAPK kinase.
      TGF-beta1-treated osteoclast-conditioned media from cells with blocked Smad
      signaling exhibited a reduced ability to support mineralization, demonstrating
      the importance of Smad signaling in this response. Parallel cultures with
      suppressed TGF-beta activation of AKT or MAPK kinase signaling retained their
      ability to elevate mineralization. These results demonstrate that TGF-beta1
      stimulates Wnt10b production in osteoclasts, which may enhance restoration of the
      bone lost during the resorptive phase of bone turnover. 

PMID- 23861380
TI  - Safety of non-therapeutic atomoxetine exposures--a national poison data system
      study.
AB  - AIMS: This study's objective is to assess the safety of non-therapeutic
      atomoxetine exposures reported to the US National Poison Database System (NPDS).
      METHODS: This is a retrospective database study of non-therapeutic single agent
      ingestions of atomoxetine in children and adults reported to the NPDS between
      2002 and 2010. RESULTS: A total of 20 032 atomoxetine exposures were reported
      during the study period, and 12 370 of these were single agent exposures. The
      median age was 9 years (interquartile range 3, 14), and 7380 were male (59.7%).
      Of the single agent exposures, 8813 (71.2%) were acute exposures, 3315 (26.8%)
      were acute-on-chronic, and 166 (1.3%) were chronic. In 10 608 (85.8%) cases,
      exposure was unintentional, in 1079 (8.7%) suicide attempts, and in 629 (5.1%)
      cases abuse. Of these cases, 3633 (29.4 %) were managed at health-care
      facilities. Acute-on-chronic exposure was associated with an increased risk of a
      suicidal reason for exposure compared with acute ingestions (odds ratio 1.44, 95%
      confidence interval 1.26-1.65). Most common clinical effects were drowsiness or
      lethargy (709 cases; 5.7%), tachycardia (555; 4.5%), and nausea (388; 3.1%).
      Major toxicity was observed in 21 cases (seizures in nine (42.9%), tachycardia in
      eight (38.1%), coma in six (28.6%), and ventricular dysrhythmia in one case
      (4.8%)). CONCLUSIONS: Non-therapeutic atomoxetine exposures were largely safe,
      but seizures were rarely observed.

PMID- 23861381
TI  - Exercise capacity and N-terminal pro-brain natriuretic peptide levels with
      biventricular vs. right ventricular pacing for atrioventricular block: results
      from the PREVENT-HF German Substudy.
AB  - AIMS: Previous studies showed unfavourable effects of right ventricular (RV)
      pacing. Ventricular pacing (VP), however, is required in many patients with
      atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV)
      remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced
      heart failure. The pre-specified PREVENT-HF German Substudy examined exercise
      capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND
      RESULTS: Patients with expected VP >=80% were randomized to RV or BIV pacing.
      Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic
      threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP.
      Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses
      of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19),
      and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis
      revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min,
      confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14
      mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to
      -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2
      persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV
      pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI
      -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90).
      CONCLUSION: Our study suggests that BIV pacing produces better exercise capacity
      over 1 year compared with RV pacing in patients without advanced heart failure
      and AV block. In contrast, we observed no significant changes of NT-proBNP.
      Larger trials will allow appraising the clinical usefulness of BIV pacing in AV
      block. ClinicalTrials.gov Identifier: NCT00170326.

PMID- 23861382
TI  - Estimating and interpreting FST: the impact of rare variants.
AB  - In a pair of seminal papers, Sewall Wright and Gustave Malecot introduced FST as
      a measure of structure in natural populations. In the decades that followed, a
      number of papers provided differing definitions, estimation methods, and
      interpretations beyond Wright's. While this diversity in methods has enabled many
      studies in genetics, it has also introduced confusion regarding how to estimate
      FST from available data. Considering this confusion, wide variation in published
      estimates of FST for pairs of HapMap populations is a cause for concern. These
      estimates changed-in some cases more than twofold-when comparing estimates from
      genotyping arrays to those from sequence data. Indeed, changes in FST from
      sequencing data might be expected due to population genetic factors affecting
      rare variants. While rare variants do influence the result, we show that this is
      largely through differences in estimation methods. Correcting for this yields
      estimates of FST that are much more concordant between sequence and genotype
      data. These differences relate to three specific issues: (1) estimating FST for a
      single SNP, (2) combining estimates of FST across multiple SNPs, and (3)
      selecting the set of SNPs used in the computation. Changes in each of these
      aspects of estimation may result in FST estimates that are highly divergent from
      one another. Here, we clarify these issues and propose solutions. 

PMID- 23861383
TI  - Bubble-seq analysis of the human genome reveals distinct chromatin-mediated
      mechanisms for regulating early- and late-firing origins.
AB  - We have devised a method for isolating virtually pure and comprehensive libraries
      of restriction fragments that contained replication initiation sites (bubbles) in
      vivo. We have now sequenced and mapped the bubble-containing fragments from
      GM06990, a near-normal EBV-transformed lymphoblastoid cell line, and have
      compared origin distributions with a comprehensive replication timing study
      recently published for this cell line. We find that early-firing origins, which
      represent ~32% of all origins, overwhelmingly represent zones, associate only
      marginally with active transcription units, are localized within large domains of
      open chromatin, and are significantly associated with DNase I hypersensitivity.
      Origin "density" falls from early- to mid-S-phase, but rises again in late S
      phase to levels only 17% lower than in early S-phase. Unexpectedly, late origin
      density calculated on the 1-Mb scale increases as a function of increasing
      chromatin compaction. Furthermore, the median efficiency of origins in late
      replicating, heterochromatic domains is only 25% lower than in early-replicating
      euchromatic loci. Thus, the activation of early- and late-firing origins must be
      regulated by quintessentially different mechanisms. The aggregate data can be
      unified into a model in which initiation site selection is driven almost entirely
      by epigenetic factors that fashion both the long-range and local chromatin
      environments, with underlying DNA sequence and local transcriptional activity
      playing only minor roles. Importantly, the comprehensive origin map we have
      prepared for GM06990 overlaps moderately well with origin maps recently reported
      for the genomes of four different human cell lines based on the distributions of
      small nascent strands. 

PMID- 23861384
TI  - Meta-analyses of studies of the human microbiota.
AB  - Our body habitat-associated microbial communities are of intense research
      interest because of their influence on human health. Because many studies of the
      microbiota are based on the same bacterial 16S ribosomal RNA (rRNA) gene target,
      they can, in principle, be compared to determine the relative importance of
      different disease/physiologic/developmental states. However, differences in
      experimental protocols used may produce variation that outweighs biological
      differences. By comparing 16S rRNA gene sequences generated from diverse studies
      of the human microbiota using the QIIME database, we found that variation in
      composition of the microbiota across different body sites was consistently larger
      than technical variability across studies. However, samples from different
      studies of the Western adult fecal microbiota generally clustered by study, and
      the 16S rRNA target region, DNA extraction technique, and sequencing platform
      produced systematic biases in observed diversity that could obscure biologically
      meaningful compositional differences. In contrast, systematic compositional
      differences in the fecal microbiota that occurred with age and between Western
      and more agrarian cultures were great enough to outweigh technical variation.
      Furthermore, individuals with ileal Crohn's disease and in their third trimester
      of pregnancy often resembled infants from different studies more than controls
      from the same study, indicating parallel compositional attributes of these
      distinct developmental/physiological/disease states. Together, these results show
      that cross-study comparisons of human microbiota are valuable when the studied
      parameter has a large effect size, but studies of more subtle effects on the
      human microbiota require carefully selected control populations and standardized
      protocols. 

PMID- 23861385
TI  - Lamin A/C-promoter interactions specify chromatin state-dependent transcription
      outcomes.
AB  - The nuclear lamina is implicated in the organization of the eukaryotic nucleus.
      Association of nuclear lamins with the genome occurs through large chromatin
      domains including mostly, but not exclusively, repressed genes. How lamin
      interactions with regulatory elements modulate gene expression in different
      cellular contexts is unknown. We show here that in human adipose tissue stem
      cells, lamin A/C interacts with distinct spatially restricted subpromoter
      regions, both within and outside peripheral and intra-nuclear lamin-rich domains.
      These localized interactions are associated with distinct transcriptional
      outcomes in a manner dependent on local chromatin modifications. Down-regulation
      of lamin A/C leads to dissociation of lamin A/C from promoters and remodels
      repressive and permissive histone modifications by enhancing transcriptional
      permissiveness, but is not sufficient to elicit gene activation. Adipogenic
      differentiation resets a large number of lamin-genome associations globally and
      at subpromoter levels and redefines associated transcription outputs. We propose
      that lamin A/C acts as a modulator of local gene expression outcome through
      interaction with adjustable sites on promoters, and that these position-dependent
      transcriptional readouts may be reset upon differentiation. 

PMID- 23861386
TI  - Modulation of endogenous antioxidant activity by resveratrol and exercise in
      mouse liver is age dependent.
AB  - Aging is a multifactorial process in which oxidative damage plays an important
      role. Resveratrol (RSV) and exercise delay some of the damages occurring during
      aging and increase life span and health span. We treated mice at different ages
      with RSV during 6 months and trained them during the last 6 weeks to determine if
      RSV and exercise induce changes in endogenous antioxidant activities in liver and
      if their effects depend on the age of the animal at the beginning of the
      intervention. Aging was accompanied by the increase in oxidative damage in liver
      especially affecting the glutathione-dependent system. Both RSV and exercise
      reversed the effect of aging and maintained high activities of glutathione,
      glutathione peroxidase, and glutathione transferase activities in old animals.
      NAD(P)H: quinone acceptor oxidoreductase activity was also increased. Modulation
      of antioxidant activities was not completely accompanied by changes at the
      protein level. Whereas glutathione peroxidase 1 protein increased in parallel to
      the higher activity in old animals, NAD(P)H: quinone acceptor oxidoreductase
      protein decreased by RSV although the activity was enhanced. Our results indicate
      that RSV and exercise revert the effect of aging in liver of old animals
      maintaining higher antioxidant activities and decreasing oxidative damage. Short
      term interventions are enough to produce beneficial effects of RSV or exercise at
      later ages.

PMID- 23861388
TI  - Calcium ions promote superoxide dismutase 1 (SOD1) aggregation into non-fibrillar
      amyloid: a link to toxic effects of calcium overload in amyotrophic lateral
      sclerosis (ALS)?
AB  - Imbalance in metal ion homeostasis is a hallmark in neurodegenerative conditions
      involving protein deposition, and amyotrophic lateral sclerosis (ALS) is no
      exception. In particular, Ca(2+) dysregulation has been shown to correlate with
      superoxide dismutase-1 (SOD1) aggregation in a cellular model of ALS. Here we
      present evidence that SOD1 aggregation is enhanced and modulated by Ca(2+). We
      show that at physiological pH, Ca(2+) induces conformational changes that
      increase SOD1 beta-sheet content, as probed by far UV CD and attenuated total
      reflectance-FTIR, and enhances SOD1 hydrophobicity, as probed by ANS fluorescence
      emission. Moreover, dynamic light scattering analysis showed that Ca(2+) boosts
      the onset of SOD1 aggregation. In agreement, Ca(2+) decreases SOD1 critical
      concentration and nucleation time during aggregation kinetics, as evidenced by
      thioflavin T fluorescence emission. Attenuated total reflectance FTIR analysis
      showed that Ca(2+) induced aggregates consisting preferentially of antiparallel
      beta-sheets, thus suggesting a modulation effect on the aggregation pathway.
      Transmission electron microscopy and analysis with conformational anti-fibril and
      anti-oligomer antibodies showed that oligomers and amyloidogenic aggregates
      constitute the prevalent morphology of Ca(2+)-induced aggregates, thus indicating
      that Ca(2+) diverts SOD1 aggregation from fibrils toward amorphous aggregates.
      Interestingly, the same heterogeneity of conformations is found in ALS-derived
      protein inclusions. We thus hypothesize that transient variations and
      dysregulation of cellular Ca(2+) levels contribute to the formation of SOD1
      aggregates in ALS patients. In this scenario, Ca(2+) may be considered as a
      pathogenic effector in the formation of ALS proteinaceous inclusions. 

PMID- 23861389
TI  - Benzalkonium chloride accelerates the formation of the amyloid fibrils of corneal
      dystrophy-associated peptides.
AB  - Corneal dystrophies are genetic disorders resulting in progressive corneal
      clouding due to the deposition of amyloid fibrils derived from keratoepithelin,
      also called transforming growth factor beta-induced protein (TGFBI). The
      formation of amyloid fibrils is often accelerated by surfactants such as sodium
      dodecyl sulfate (SDS). Most eye drops contain benzalkonium chloride (BAC), a
      cationic surfactant, as a preservative substance. In the present study, we aimed
      to reveal the role of BAC in the amyloid fibrillation of keratoepithelin-derived
      peptides in vitro. We used three types of 22-residue synthetic peptides covering
      Leu110-Glu131 of the keratoepithelin sequence: an R-type peptide with wild-type
      R124, a C-type peptide with C124 associated with lattice corneal dystrophy type
      I, and a H-type peptide with H124 associated with granular corneal dystrophy type
      II. The time courses of spontaneous amyloid fibrillation and seed-dependent
      fibril elongation were monitored in the presence of various concentrations of BAC
      or SDS using thioflavin T fluorescence. BAC and SDS accelerated the fibrillation
      of all synthetic peptides in the absence and presence of seeds. Optimal
      acceleration occurred near the CMC, which suggests that the unstable and dynamic
      interactions of keratoepithelin peptides with amphipathic surfactants led to the
      formation of fibrils. These results suggest that eye drops containing BAC may
      deteriorate corneal dystrophies and that those without BAC are preferred
      especially for patients with corneal dystrophies. 

PMID- 23861390
TI  - Peroxynitrite, a stealthy biological oxidant.
AB  - Peroxynitrite is the product of the diffusion-controlled reaction of nitric oxide
      and superoxide radicals. Peroxynitrite, a reactive short-lived peroxide with a
      pKa of 6.8, is a good oxidant and nucleophile. It also yields secondary free
      radical intermediates such as nitrogen dioxide and carbonate radicals. Much of
      nitric oxide- and superoxide-dependent cytotoxicity resides on peroxynitrite,
      which affects mitochondrial function and triggers cell death via oxidation and
      nitration reactions. Peroxynitrite is an endogenous toxicant but is also a
      cytotoxic effector against invading pathogens. The biological chemistry of
      peroxynitrite is modulated by endogenous antioxidant mechanisms and neutralized
      by synthetic compounds with peroxynitrite-scavenging capacity. 

PMID- 23861391
TI  - SH3-binding protein 5 mediates the neuroprotective effect of the secreted
      bioactive peptide humanin by inhibiting c-Jun NH2-terminal kinase.
AB  - Humanin is a secreted bioactive peptide that suppresses cell toxicity caused by a
      variety of insults. The neuroprotective effect of Humanin against Alzheimer
      disease (AD)-related death is mediated by the binding of Humanin to its
      heterotrimeric Humanin receptor composed of ciliary neurotrophic receptor alpha,
      WSX-1, and gp130, as well as the activation of intracellular signaling pathways
      including a JAK2 and STAT3 signaling axis. Despite the elucidation of the
      signaling pathways by which Humanin mediates its neuroprotection, the
      transcriptional targets of Humanin that behaves as effectors of Humanin remains
      undefined. In the present study, Humanin increased the mRNA and protein
      expression of SH3 domain-binding protein 5 (SH3BP5), which has been known to be a
      JNK interactor, in neuronal cells. Similar to Humanin treatment, overexpression
      of SH3BP5 inhibited AD-related neuronal death, while siRNA-mediated knockdown of
      endogenous SH3BP5 expression attenuated the neuroprotective effect of Humanin.
      These results indicate that SH3BP5 is a downstream effector of Humanin.
      Furthermore, biochemical analysis has revealed that SH3BP5 binds to JNK and
      directly inhibits JNK through its two putative mitogen-activated protein kinase
      interaction motifs (KIMs). 

PMID- 23861392
TI  - Mediator of ERBB2-driven cell motility (MEMO) promotes extranuclear estrogen
      receptor signaling involving the growth factor receptors IGF1R and ERBB2.
AB  - In addition to nuclear estrogen receptor (ER) acting as a transcription factor,
      extranuclear ER also plays an important role in cancer cell growth regulation
      through activation of kinase cascades. However, the molecular mechanisms by which
      extranuclear ER exerts its function are still poorly understood. Here, we report
      that mediator of ERBB2-driven cell motility (MEMO) regulates extranuclear
      functions of ER. MEMO physically and functionally interacted with ER. Through its
      interaction with the growth factor receptors IGF1R and ERBB2, MEMO mediated
      extranuclear functions of ER, including activation of mitogen-activated protein
      kinase (MAPK) and protein kinase B/AKT, two important growth regulatory protein
      kinases, and integration of function with nuclear ER. Activation of MAPK and AKT
      was responsible for MEMO modulation of ER phosphorylation and estrogen-responsive
      gene expression. Moreover, MEMO increased anchorage-dependent and -independent
      growth of ER-positive breast cancer cells in vitro and was required for estrogen
      induced breast tumor growth in nude mice. Together, our studies identified MEMO
      as a new component of extranuclear ER signalosome and suggest an essential role
      for MEMO in the regulation of ER-positive breast cancer cell growth. 

PMID- 23861394
TI  - Lipid segregation and membrane budding induced by the peripheral membrane binding
      protein annexin A2.
AB  - The formation of dynamic membrane microdomains is an important phenomenon in many
      signal transduction and membrane trafficking events. It is driven by intrinsic
      properties of membrane lipids and integral as well as membrane-associated
      proteins. Here we analyzed the ability of one peripherally associated membrane
      protein, annexin A2 (AnxA2), to induce the formation of phosphatidylinositol 4,5
      bisphosphate (PI(4,5)P2)-rich domains in giant unilamellar vesicles (GUVs) of
      complex lipid composition. AnxA2 is a cytosolic protein that can bind PI(4,5)P2
      and other acidic phospholipids in a Ca(2+)-dependent manner and that has been
      implicated in cellular membrane dynamics in endocytosis and exocytosis. We show
      that AnxA2 binding to GUVs induces lipid phase separation and the recruitment of
      PI(4,5)P2, cholesterol and glycosphingolipids into larger clusters. This property
      is observed for the full-length monomeric protein, a mutant derivative comprising
      the C-terminal protein core domain and for AnxA2 residing in a heterotetrameric
      complex with its intracellular binding partner S100A10. All AnxA2 derivatives
      inducing PI(4,5)P2 clustering are also capable of forming interconnections
      between PI(4,5)P2-rich microdomains of adjacent GUVs. Furthermore, they can
      induce membrane indentations rich in PI(4,5)P2 and inward budding of these
      membrane domains into the lumen of GUVs. This inward vesiculation is specific for
      AnxA2 and not shared with other PI(4,5)P2-binding proteins such as the pleckstrin
      homology (PH) domain of phospholipase Cdelta1. Together our results indicate that
      annexins such as AnxA2 can efficiently induce membrane deformations after lipid
      segregation, a mechanism possibly underlying annexin functions in membrane
      trafficking. 

PMID- 23861393
TI  - Regulation of protein function and signaling by reversible cysteine S
      nitrosylation.
AB  - NO is a versatile free radical that mediates numerous biological functions within
      every major organ system. A molecular pathway by which NO accomplishes functional
      diversity is the selective modification of protein cysteine residues to form S
      nitrosocysteine. This post-translational modification, S-nitrosylation, impacts
      protein function, stability, and location. Despite considerable advances with
      individual proteins, the in vivo biological chemistry, the structural elements
      that govern the selective S-nitrosylation of cysteine residues, and the potential
      overlap with other redox modifications are unknown. In this minireview, we
      explore the functional features of S-nitrosylation at the proteome level and the
      structural diversity of endogenously modified residues, and we discuss the
      potential overlap and complementation that may exist with other cysteine
      modifications. 

PMID- 23861396
TI  - Structural basis of a physical blockage mechanism for the interaction of response
      regulator PmrA with connector protein PmrD from Klebsiella pneumoniae.
AB  - In bacteria, the two-component system is the most prevalent for sensing and
      transducing environmental signals into the cell. The PmrA-PmrB two-component
      system, responsible for sensing external stimuli of high Fe(3+) and mild acidic
      conditions, can control the genes involved in lipopolysaccharide modification and
      polymyxin resistance in pathogens. In Klebsiella pneumoniae, the small basic
      connector protein PmrD protects phospho-PmrA and prolongs the expression of PmrA
      activated genes. We previously determined the phospho-PmrA recognition mode of
      PmrD. However, how PmrA interacts with PmrD and prevents its dephosphorylation
      remains unknown. To address this question, we solved the x-ray crystal structure
      of the N-terminal receiver domain of BeF3(-)-activated PmrA (PmrA(N)) at 1.70 A.
      With this structure, we applied the data-driven docking method based on NMR
      chemical shift perturbation to generate the complex model of PmrD-PmrA(N), which
      was further validated by site-directed spin labeling experiments. In the complex
      model, PmrD may act as a blockade to prevent phosphatase from contacting with the
      phosphorylation site on PmrA.

PMID- 23861395
TI  - Oxidant sensing by reversible disulfide bond formation.
AB  - Maintenance of the cellular redox balance is crucial for cell survival. An
      increase in reactive oxygen, nitrogen, or chlorine species can lead to oxidative
      stress conditions, potentially damaging DNA, lipids, and proteins. Proteins are
      very sensitive to oxidative modifications, particularly methionine and cysteine
      residues. The reversibility of some of these oxidative protein modifications
      makes them ideally suited to take on regulatory roles in protein function. This
      is especially true for disulfide bond formation, which has the potential to
      mediate extensive yet fully reversible structural and functional changes, rapidly
      adjusting the protein's activity to the prevailing oxidant levels. 

PMID- 23861397
TI  - Dual role of BAR domain-containing proteins in regulating vesicle release
      catalyzed by the GTPase, dynamin-2.
AB  - Dynamin-2 (Dyn2) is ubiquitously expressed and catalyzes membrane fission during
      clathrin-mediated endocytosis in nonneuronal cells. We have previously shown that
      Dyn2 inefficiently generates membrane curvature and only mediates fission of
      highly curved membranes. This led to the hypothesis that other endocytic
      accessory proteins (EAPs) generate curvature needed to sculpt a sufficiently
      narrow neck to trigger Dyn2 assembly and fission. Candidates for this activity
      are EAPs that bind to the dynamin proline/arginine-rich domain (PRD) through
      their SH3 (src homology-3) domains and also encode curvature-generating BAR
      (Bin/Amphiphysin/Rvs) domains. We show that at low concentrations, amphiphysin
      and endophilin, but not SNX9 or the curvature-generating epsin N-terminal
      homology (ENTH) domain, are able to generate tubules from planar membrane
      templates and to synergize with Dyn2DeltaPRD to catalyze vesicle release.
      Unexpectedly, SH3-PRD interactions were inhibitory and reciprocally regulate
      scaffold assembly. Of the three proteins studied, only full-length amphiphysin
      functions synergistically with full-length Dyn2 to catalyze vesicle release. The
      differential activity of these proteins correlates with the relative potency of
      their positive, curvature-generating activity, and the negative regulatory
      effects mediated by SH3 domain interactions. Our findings reveal opportunities
      for the spatio-temporal coordination of membrane curvature generation, dynamin
      assembly, and fission during clathrin-mediated endocytosis. 

PMID- 23861398
TI  - beta-Transducin repeat-containing protein 1 (beta-TrCP1)-mediated silencing
      mediator of retinoic acid and thyroid hormone receptor (SMRT) protein degradation
      promotes tumor necrosis factor alpha (TNFalpha)-induced inflammatory gene
      expression.
AB  - Cytokine modulation of the endothelium is considered an important contributor to
      the inflammation response. TNFalpha is an early response gene during the
      initiation of inflammation. However, the detailed mechanism by which TNFalpha
      induces proinflammatory gene expression is not completely understood. In this
      report, we demonstrate that silencing mediator of retinoic acid and thyroid
      hormone receptor (SMRT) represses the expression of a subset of TNFalpha target
      genes in human umbilical vein endothelial cells. Upon TNFalpha stimulation, we
      observed an increase in the E3 ubiquitin ligase beta-TrCP1 and a decrease in SMRT
      protein levels. We show that beta-TrCP1 interacts with SMRT in a phosphorylation
      independent manner and cooperates with the E2 ubiquitin-conjugating enzyme E2D2
      to promote ubiquitination-dependent SMRT degradation. Knockdown of beta-TrCP1
      increases SMRT protein accumulation, increases SMRT association with its targeted
      promoters, and decreases SMRT target gene expression. Taken together, our results
      support a model in which TNFalpha-induced beta-TrCP1 accumulation promotes SMRT
      degradation and the subsequent induction of proinflammatory gene expression. 

PMID- 23861400
TI  - Modulation of GluK2a subunit-containing kainate receptors by 14-3-3 proteins.
AB  - Kainate receptors (KARs) are one of the ionotropic glutamate receptors that
      mediate excitatory postsynaptic currents (EPSCs) with characteristically slow
      kinetics. Although mechanisms for the slow kinetics of KAR-EPSCs are not totally
      understood, recent evidence has implicated a regulatory role of KAR-associated
      proteins. Here, we report that decay kinetics of GluK2a-containing receptors is
      modulated by closely associated 14-3-3 proteins. 14-3-3 binding requires PKC
      dependent phosphorylation of serine residues localized in the carboxyl tail of
      the GluK2a subunit. In transfected cells, 14-3-3 binding to GluK2a slows
      desensitization kinetics of both homomeric GluK2a and heteromeric GluK2a/GluK5
      receptors. Moreover, KAR-EPSCs at mossy fiber-CA3 synapses decay significantly
      faster in the 14-3-3 functional knock-out mice. Collectively, these results
      demonstrate that 14-3-3 proteins are an important regulator of GluK2a-containing
      KARs and may contribute to the slow decay kinetics of native KAR-EPSCs. 

PMID- 23861401
TI  - Posttranslational modifications in type I collagen from different tissues
      extracted from wild type and prolyl 3-hydroxylase 1 null mice.
AB  - Type I collagen extracted from tendon, skin, and bone of wild type and prolyl 3
      hydroxylase 1 (P3H1) null mice shows distinct patterns of 3-hydroxylation and
      glycosylation of hydroxylysine residues. The A1 site (Pro-986) in the alpha1
      chain of type I collagen is almost completely 3-hydroxylated in every tissue of
      the wild type mice. In contrast, no 3-hydroxylation of this proline residue was
      found in P3H1 null mice. Partial 3-hydroxylation of the A3 site (Pro-707) was
      present in tendon and bone, but absent in skin in both alpha-chains of the wild
      type animals. Type I collagen extracted from bone of P3H1 null mice shows a large
      reduction in 3-hydroxylation of the A3 site in both alpha-chains, whereas type I
      collagen extracted from tendon of P3H1 null mice shows little difference as
      compared with wild type. These results demonstrate that the A1 site in type I
      collagen is exclusively 3-hydroxylated by P3H1, and presumably, this enzyme is
      required for the 3-hydroxylation of the A3 site of both alpha-chains in bone but
      not in tendon. The increase in glycosylation of hydroxylysine in P3H1 null mice
      in bone was found to be due to an increased occupancy of normally glycosylated
      sites. Despite the severe disorganization of collagen fibrils in adult tissues,
      the D-period of the fibrils is unchanged. Tendon fibrils of newborn P3H1 null
      mice are well organized with only a slight increase in diameter. The absence of 3
      hydroxyproline and/or the increased glycosylation of hydroxylysine in type I
      collagen disturbs the lateral growth of the fibrils. 

PMID- 23861399
TI  - Causes and consequences of cysteine S-glutathionylation.
AB  - Post-translational S-glutathionylation occurs through the reversible addition of
      a proximal donor of glutathione to thiolate anions of cysteines in target
      proteins, where the modification alters molecular mass, charge, and
      structure/function and/or prevents degradation from sulfhydryl overoxidation or
      proteolysis. Catalysis of both the forward (glutathione S-transferase P) and
      reverse (glutaredoxin) reactions creates a functional cycle that can also
      regulate certain protein functional clusters, including those involved in redox
      dependent cell signaling events. For translational application, S
      glutathionylated serum proteins may be useful as biomarkers in individuals (who
      may also have polymorphic expression of glutathione S-transferase P) exposed to
      agents that cause oxidative or nitrosative stress. 

PMID- 23861402
TI  - Introduction to the thematic minireview series on redox-active protein
      modifications and signaling.
AB  - The dynamics of redox metabolism necessitate cellular strategies for sensing
      redox changes and for responding to them. A common mechanism for receiving and
      transmitting redox changes is via reversible modifications of protein cysteine
      residues. A plethora of cysteine modifications have been described, including
      sulfenylation, glutathionylation, and disulfide formation. These post
      translational modifications have the potential to alter protein structure and/or
      function and to modulate cellular processes ranging from division to death and
      from circadian rhythms to secretion. The focus of this thematic minireview series
      is cysteine modifications in response to reactive oxygen and nitrogen species. 

PMID- 23861403
TI  - A Ca2+-dependent mechanism of neuronal survival mediated by the microtubule
      associated protein p600.
AB  - In acute and chronic neurodegeneration, Ca(2+) mishandling and disruption of the
      cytoskeleton compromise neuronal integrity, yet abnormalities in the signaling
      roles of cytoskeletal proteins remain largely unexplored. We now report that the
      microtubule-associated protein p600 (also known as UBR4) promotes neuronal
      survival. Following depletion of p600, glutamate-induced Ca(2+) influx through
      NMDA receptors, but not AMPA receptors, initiates a degenerative process
      characterized by endoplasmic reticulum fragmentation and endoplasmic reticulum
      Ca(2+) release via inositol 1,4,5-trisphosphate receptors. Downstream of NMDA
      receptors, p600 associates with the calmodulin.calmodulin-dependent protein
      kinase IIalpha complex. A direct and atypical p600/calmodulin interaction is
      required for neuronal survival. Thus, p600 counteracts specific Ca(2+)-induced
      death pathways through regulation of Ca(2+) homeostasis and signaling. 

PMID- 23861406
TI  - A multimodal examination of sexual interest in children: a comparison of sex
      offenders and nonsex offenders.
AB  - Research and theoretical models have consistently identified sexual interest in
      children as a key factor involved in child sexual offending. However, there is
      only moderate agreement in the diagnosis of pedophilia and different assessment
      methods identify different offenders as pedophiles. The current study examined
      the discriminative and convergent validity of three different measures of sexual
      interest in children. Participants included sex offenders and nonsex offenders
      recruited from federal prisons (i.e., offenders serving sentences of more than 2
      years) in Ontario, Canada. Child molesters' responses (n = 35) were not
      significantly different from nonsex offenders (n = 21) on an implicit measure of
      sexual interest in children (Sexual Attraction to Children Implicit Association
      Test [SAC-IAT] d = 0.44, 95% CI [-0.11, 0.99]), but differed on the self-report
      (Sexual Interest Profiling System; d = 0.83, 95% CI [0.27, 1.39]) and viewing
      time (d = 1.15, 95% CI [0.54, 1.75]) measures. Findings did not provide clear
      support for the superiority of a multimodal approach, possibly due to the
      relatively small sample. More often than not, convergence between the three
      measures was observed (n = 74). Findings from the present study are an important
      step toward understanding the relationship between different measures of sexual
      interest in children and establishing their validity. 

PMID- 23861404
TI  - BBA70 of Borrelia burgdorferi is a novel plasminogen-binding protein.
AB  - The Lyme disease spirochete Borrelia burgdorferi lacks endogenous, surface
      exposed proteases. In order to efficiently disseminate throughout the host and
      penetrate tissue barriers, borreliae rely on recruitment of host proteases, such
      as plasmin(ogen). Here we report the identification of a novel plasminogen
      binding protein, BBA70. Binding of plasminogen is dose-dependent and is affected
      by ionic strength. The BBA70-plasminogen interaction is mediated by lysine
      residues, primarily located in a putative C-terminal alpha-helix of BBA70. These
      lysine residues appear to interact with the lysine-binding sites in plasminogen
      kringle domain 4 because a deletion mutant of plasminogen lacking that domain was
      unable to bind to BBA70. Bound to BBA70, plasminogen activated by urokinase-type
      plasminogen activator was able to degrade both a synthetic chromogenic substrate
      and the natural substrate fibrinogen. Furthermore, BBA70-bound plasmin was able
      to degrade the central complement proteins C3b and C5 and inhibited the
      bacteriolytic effects of complement. Consistent with these functional activities,
      BBA70 is located on the borrelial outer surface. Additionally, serological
      evidence demonstrated that BBA70 is produced during mammalian infection. Taken
      together, recruitment and activation of plasminogen could play a beneficial role
      in dissemination of B. burgdorferi in the human host and may possibly aid the
      spirochete in escaping the defense mechanisms of innate immunity. 

PMID- 23861405
TI  - The redox biochemistry of protein sulfenylation and sulfinylation.
AB  - Controlled generation of reactive oxygen species orchestrates numerous
      physiological signaling events (Finkel, T. (2011) Signal transduction by reactive
      oxygen species. J. Cell Biol. 194, 7-15). A major cellular target of reactive
      oxygen species is the thiol side chain (RSH) of Cys, which may assume a wide
      range of oxidation states (i.e. -2 to +4). Within this context, Cys sulfenic (Cys
      SOH) and sulfinic (Cys-SO2H) acids have emerged as important mechanisms for
      regulation of protein function. Although this area has been under investigation
      for over a decade, the scope and biological role of sulfenic/sulfinic acid
      modifications have been recently expanded with the introduction of new tools for
      monitoring cysteine oxidation in vitro and directly in cells. This minireview
      discusses selected recent examples of protein sulfenylation and sulfinylation
      from the literature, highlighting the role of these post-translational
      modifications in cell signaling. 

PMID- 23861407
TI  - Web based surveillance systems could improve disease detection and the response
      to emerging disease events.

PMID- 23861408
TI  - Starting vocational rehabilitation early after stroke.

PMID- 23861409
TI  - Discontinue treatment with nicorandil associated with ulceration to avoid major
      reconstructive surgery.

PMID- 23861410
TI  - Transfusing blood safely and appropriately.

PMID- 23861411
TI  - Involving patients in drug licensing decisions.

PMID- 23861412
TI  - Providing balanced information where uncertainty exists.

PMID- 23861415
TI  - Please give more details in the Minerva case of nicorandil induced perianal
      ulceration.

PMID- 23861416
TI  - Authors' reply to Herxheimer.

PMID- 23861417
TI  - Dancer makes unjustified leaps.

PMID- 23861418
TI  - Time to put our coats back on and be counted.

PMID- 23861419
TI  - Importance of visual impairment after stroke not recognised yet again.

PMID- 23861420
TI  - What will follow the millennium development goals?

PMID- 23861421
TI  - Don't forget about constipation with opioid treatment of chronic non-cancer pain.

PMID- 23861422
TI  - Prescribe opioids for chronic non-cancer pain with care for the sake of patients
      and the community.

PMID- 23861423
TI  - Might pelvic examination be helpful in first trimester miscarriage?

PMID- 23861424
TI  - Author's reply to Vaughan.

PMID- 23861425
TI  - Act now to prevent re-emergence of congenital rubella.

PMID- 23861427
TI  - Let's hope that the pendulum swings back to white coat and formal attire.

PMID- 23861426
TI  - The next step in controlling HBV in China.

PMID- 23861428
TI  - "Scrubs" are no answer.

PMID- 23861429
TI  - Involving patients in setting the research agenda in drug addiction.

PMID- 23861430
TI  - Has the Data Protection Act been misused as a fig leaf for medical secrecy?

PMID- 23861431
TI  - Dietary fats and breast cancer risk.

PMID- 23861432
TI  - Higher drug prices will boost development of personalised medicine, says new
      report.

PMID- 23861433
TI  - Doctors object to bill that would allow force feeding of hunger striking
      prisoners.

PMID- 23861434
TI  - Liverpool care pathway is scrapped after review finds it was not well used.

PMID- 23861435
TI  - Regulator says Tameside must make urgent improvements.

PMID- 23861436
TI  - Regulation of circadian clocks by redox homeostasis.
AB  - Living organisms possess biological clocks that resonate with environmental
      cycles in light, temperature, and food availability. Recently, circadian
      oscillations in the redox state of peroxiredoxin have been described as an
      additional non-transcriptional timekeeping mechanism. Of note, this redox cycle
      is conserved in both prokaryotes and eukaryotes. How the classical "transcription
      translation feedback loop" model and this redox oscillation are related is still
      poorly understood. In this minireview, we describe the most recent evidence
      pointing to cross-talk between the circadian clock and the redox status of the
      cell. 

PMID- 23861438
TI  - Ireland's parliament votes to allow "life saving" abortion.

PMID- 23861439
TI  - Texas governor promises to sign abortion law that will close most clinics.

PMID- 23861437
TI  - The redox proteome.
AB  - The redox proteome consists of reversible and irreversible covalent modifications
      that link redox metabolism to biologic structure and function. These
      modifications, especially of Cys, function at the molecular level in protein
      folding and maturation, catalytic activity, signaling, and macromolecular
      interactions and at the macroscopic level in control of secretion and cell shape.
      Interaction of the redox proteome with redox-active chemicals is central to
      macromolecular structure, regulation, and signaling during the life cycle and has
      a central role in the tolerance and adaptability to diet and environmental
      challenges. 

PMID- 23861440
TI  - Public health body quits responsibility deal over government's failure to act on
      tobacco and alcohol.

PMID- 23861441
TI  - Comparing hormone therapy effects in two RCTs and two large observational studies
      that used similar methods for comprehensive data collection and outcome
      assessment.
AB  - OBJECTIVES: Prospective observational studies (OSs) that collect adequate
      information about confounders can validly assess treatment consequences. However,
      what constitutes adequate information is unknown. This study investigated whether
      the extensive information collected by the Women's Health Initiative (WHI) in two
      OSs and two randomised controlled trials (RCTs) was adequate. DESIGN: Secondary
      analysis of WHI data. Cox regression was used to select from all baseline risk
      factors those that best predicted outcome. Cox regression that included these
      risk factors was used for two types of analyses: (1) comparing RCT and OS
      assessments of the effects of hormone therapy on outcome for participants with
      specific characteristics and (2) evaluating whether adjustment for measured
      confounders could eliminate outcome differences among datasets. SETTING: The WHI
      included more than 800 baseline risk factors and outcomes during a median follow
      up of 8 years. PARTICIPANTS: 151 870 postmenopausal women ages 50-79. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Myocardial infarction and stroke. RESULTS: RCT and OS
      results differed for the association of hormone therapy with outcome after
      adjusting for confounding factors and stratifying on factors that were
      hypothesised to modulate the effects of hormone therapy (eg, age and time since
      menopause) or that empirically modulated the effects of hormone therapy in this
      dataset (eg, blood pressure, previous coronary revascularisation and private
      medical insurance). Some of the four WHI datasets had significantly worse
      outcomes than others even after adjusting for risk and stratifying by type of
      hormone therapy, for example, the risk-adjusted HR for myocardial infarction was
      1.37 (p<0.0001) in an RCT placebo group compared with an OS group not taking
      hormone therapy. CONCLUSIONS: Apparently the WHI did not collect sufficient
      information to give reliable assessments of treatment effects. If the WHI did not
      collect sufficient data, it is likely that few OSs collect sufficient
      information.

PMID- 23861442
TI  - An intronic structure enabled by a long-distance interaction serves as a novel
      target for splicing correction in spinal muscular atrophy.
AB  - Here, we report a long-distance interaction (LDI) as a critical regulator of
      alternative splicing of Survival Motor Neuron 2 (SMN2) exon 7, skipping of which
      is linked to spinal muscular atrophy (SMA), a leading genetic disease of children
      and infants. We show that this LDI is linked to a unique intra-intronic structure
      that we term internal stem through LDI-1 (ISTL1). We used site-specific mutations
      and Selective 2'-Hydroxyl Acylation analyzed by Primer Extension to confirm the
      formation and functional significance of ISTL1. We demonstrate that the
      inhibitory effect of ISTL1 is independent of hnRNP A1/A2B1 and PTB1 previously
      implicated in SMN2 exon 7 splicing. We show that an antisense oligonucleotide
      mediated sequestration of the 3' strand of ISTL1 fully corrects SMN2 exon 7
      splicing and restores high levels of SMN and Gemin2, a SMN-interacting protein,
      in SMA patient cells. Our results also reveal that the 3' strand of ISTL1 and
      upstream sequences constitute an inhibitory region that we term intronic splicing
      silencer N2 (ISS-N2). This is the first report to demonstrate a critical role of
      a structure-associated LDI in splicing regulation of an essential gene linked to
      a genetic disease. Our findings expand the repertoire of potential targets for an
      antisense oligonucleotide-mediated therapy of SMA. 

PMID- 23861443
TI  - Dystrophin rescue by trans-splicing: a strategy for DMD genotypes not eligible
      for exon skipping approaches.
AB  - RNA-based therapeutic approaches using splice-switching oligonucleotides have
      been successfully applied to rescue dystrophin in Duchenne muscular dystrophy
      (DMD) preclinical models and are currently being evaluated in DMD patients.
      Although the modular structure of dystrophin protein tolerates internal
      deletions, many mutations that affect nondispensable domains of the protein
      require further strategies. Among these, trans-splicing technology is
      particularly attractive, as it allows the replacement of any mutated exon by its
      normal version as well as introducing missing exons or correcting duplication
      mutations. We have applied such a strategy in vitro by using cotransfection of
      pre-trans-splicing molecule (PTM) constructs along with a reporter minigene
      containing part of the dystrophin gene harboring the stop-codon mutation found in
      the mdx mouse model of DMD. Optimization of the different functional domains of
      the PTMs allowed achieving accurate and efficient trans-splicing of up to 30% of
      the transcript encoded by the cotransfected minigene. Optimized parameters
      included mRNA stabilization, choice of splice site sequence, inclusion of exon
      splice enhancers and artificial intronic sequence. Intramuscular delivery of
      adeno-associated virus vectors expressing PTMs allowed detectable levels of
      dystrophin in mdx and mdx4Cv, illustrating that a given PTM can be suitable for a
      variety of mutations. 

PMID- 23861444
TI  - A versatile microsatellite instability reporter system in human cells.
AB  - Here, we report the investigation of microsatellite instability (MSI) in human
      cells with a newly developed reporter system based on fluorescence. We composed a
      vector into which microsatellites of different lengths and nucleotide composition
      can be introduced between a functional copy of the fluorescent protein mCherry
      and an out-of-frame copy of EGFP; in vivo frameshifting will lead to EGFP
      expression, which can be quantified by fluorescence activated cell sorting
      (FACS). Via targeted recombineering, single copy reporters were introduced in
      HEK293 and MCF-7 cells. We found predominantly -1 and +1 base pair frameshifts,
      the levels of which are kept in tune by mismatch repair. We show that tract
      length and composition greatly influences MSI. In contrast, a tracts' potential
      to form a G-quadruplex structure, its strand orientation or its transcriptional
      status is not affecting MSI. We further validated the functionality of the
      reporter system for screening microsatellite mutagenicity of compounds and for
      identifying modifiers of MSI: using a retroviral miRNA expression library, we
      identified miR-21, which targets MSH2, as a miRNA that induces MSI when
      overexpressed. Our data also provide proof of principle for the strategy of
      combining fluorescent reporters with next-generation sequencing technology to
      identify genetic factors in specific pathways. 

PMID- 23861445
TI  - Genome-wide hydroxymethylation tested using the HELP-GT assay shows
      redistribution in cancer.
AB  - 5-hydroxymethylcytosine (5-hmC) is a recently discovered epigenetic modification
      that is altered in cancers. Genome-wide assays for 5-hmC determination are needed
      as many of the techniques for 5-methylcytosine (5-mC) determination, including
      methyl-sensitive restriction digestion and bisulfite sequencing cannot
      distinguish between 5-mC and 5-hmC. Glycosylation of 5-hmC residues by beta
      glucosyl transferase (beta-GT) can make CCGG residues insensitive to digestion by
      MspI. Restriction digestion by HpaII, MspI or MspI after beta-GT conversion,
      followed by adapter ligation, massive parallel sequencing and custom
      bioinformatic analysis allowed us determine distribution of 5-mC and 5-hmC at
      single base pair resolution at MspI restriction sites. The resulting HpaII tiny
      fragment Enrichment by Ligation-mediated PCR with beta-GT (HELP-GT) assay
      identified 5-hmC loci that were validated at global level by liquid
      chromatography-mass spectrometry (LC-MS) and the locus-specific level by
      quantitative reverse transcriptase polymerase chain reaction of 5-hmC pull-down
      DNA. Hydroxymethylation at both promoter and intragenic locations correlated
      positively with gene expression. Analysis of pancreatic cancer samples revealed
      striking redistribution of 5-hmC sites in cancer cells and demonstrated
      enrichment of this modification at many oncogenic promoters such as GATA6. The
      HELP-GT assay allowed global determination of 5-hmC and 5-mC from low amounts of
      DNA and with the use of modest sequencing resources. Redistribution of 5-hmC seen
      in cancer highlights the importance of determination of this modification in
      conjugation with conventional methylome analysis. 

PMID- 23861446
TI  - miR-7a alleviates the maintenance of neuropathic pain through regulation of
      neuronal excitability.
AB  - Neuronal damage in the somatosensory system causes intractable chronic
      neuropathic pain. Plastic changes in sensory neuron excitability are considered
      the cellular basis of persistent pain. Non-coding microRNAs modulate specific
      gene translation to impact on diverse cellular functions and their dysregulation
      causes various diseases. However, their significance in adult neuronal functions
      and disorders is still poorly understood. Here, we show that miR-7a is a key
      functional RNA sustaining the late phase of neuropathic pain through regulation
      of neuronal excitability in rats. In the late phase of neuropathic pain,
      microarray analysis identified miR-7a as the most robustly decreased microRNA in
      the injured dorsal root ganglion. Moreover, local induction of miR-7a, using an
      adeno-associated virus vector, in sensory neurons of injured dorsal root
      ganglion, suppressed established neuropathic pain. In contrast, miR-7a
      overexpression had no effect on acute physiological or inflammatory pain.
      Furthermore, miR-7a downregulation was sufficient to cause pain-related
      behaviours in intact rats. miR-7a targeted the beta2 subunit of the voltage-gated
      sodium channel, and decreased miR-7a associated with neuropathic pain caused
      increased beta2 subunit protein expression, independent of messenger RNA levels.
      Consistently, miR-7a overexpression in primary sensory neurons of injured dorsal
      root ganglion suppressed increased beta2 subunit expression and normalized long
      lasting hyperexcitability of nociceptive neurons. These findings demonstrate miR
      7a downregulation is causally involved in maintenance of neuropathic pain through
      regulation of neuronal excitability, and miR-7a replenishment offers a novel
      therapeutic strategy specific for chronic neuropathic pain. 

PMID- 23861447
TI  - Editor's note.

PMID- 23861448
TI  - Coronary artery calcium scores using nongated computed tomography: what to do
      with incidental results?

PMID- 23861449
TI  - Net reclassification improvement and integrated discrimination improvement: new
      standards for evaluating the incremental value of stress imaging for risk
      assessment.

PMID- 23861450
TI  - Dynamic assessment of stenotic valvular heart disease by stress echocardiography.

PMID- 23861451
TI  - Use of cardiac magnetic resonance and echocardiography in population-based
      studies: why, where, and when?

PMID- 23861452
TI  - Computed tomographic imaging of transcatheter aortic valve replacement for
      prediction and prevention of procedural complications.

PMID- 23861453
TI  - Increased metabolic activity highlighted by positron emission tomography/computed
      tomography in the wall of the dissected ascending aorta in a patient with Horton
      disease.

PMID- 23861454
TI  - Letter by Kharabish and Fratz regarding article, "Implications of early aortic
      stiffening in patients with transposition of the great arteries after arterial
      switch operation".

PMID- 23861455
TI  - Response to letter regarding article, "Implications of early aortic stiffening in
      patients with transposition of the great arteries after arterial switch
      operation".

PMID- 23861456
TI  - Letter by Iles and Taylor regarding article, "Comprehensive validation of
      cardiovascular magnetic resonance techniques for the assessment of myocardial
      extracellular volume".

PMID- 23861457
TI  - Response to letter regarding article, "Comprehensive validation of cardiovascular
      magnetic resonance techniques for the assessment of myocardial extracellular
      volume".

PMID- 23861458
TI  - Neurodevelopmental and body composition outcomes in children with congenital
      hypothyroidism treated with high-dose initial replacement and close monitoring.
AB  - BACKGROUND: Despite newborn screening and early levothyroxine replacement, there
      are continued reports of mild neurocognitive impairment in children with
      congenital hypothyroidism (CHT). In Auckland, New Zealand, cases are identified
      by a neonatal screening program with rapid institution of high-dose levothyroxine
      replacement (10-15 MUg/kg.d), producing prompt normalization of thyroid function.
      Subsequently, frequent monitoring and dose alterations are performed for 2 years.
      We aimed to assess whether the Auckland treatment strategy prevents impairment of
      intellectual and motor development. METHODS: This study encompassed all children
      with CHT born in 1993-2006 in Auckland and their siblings. Neurocognitive
      assessments included the following: 1) intelligence quotient via Weschler
      Preschool and Primary Scale of Intelligence III or Weschler Intelligence Scale
      for Children IV; 2) Movement Assessment Battery for Children; and 3) Beery
      Developmental Test of Visual-Motor Integration. Body composition was assessed by
      dual-energy x-ray absorptiometry. RESULTS: Forty-four CHT cases and 53 sibling
      controls aged 9.6 +/- 3.9 years were studied. Overall intelligence quotient was
      similar among CHT cases and controls (95.2 vs 98.6; P = .20), and there were also
      no differences in motor function. Severity of CHT did not influence outcome, but
      greater time to normalize free T4 was associated with worse motor balance. There
      were no differences in anthropometry or body composition between groups.
      CONCLUSIONS: These findings suggest that a strategy of rapidly identifying and
      treating infants with CHT using high-dose levothyroxine replacement is associated
      with normal intellectual and motor development. The subtle negative impact on
      motor function associated with time to normalize free T4 levels is consistent
      with benefit from rapid initial correction.

PMID- 23861459
TI  - Unusual case of solitary functioning bone metastasis from a "parathyroid
      adenoma": imagiologic diagnosis and treatment with percutaneous vertebroplasty-
      case report and literature review.
AB  - BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy that accounts
      for a small percentage of patients with primary hyperparathyroidism. Here, an
      unusual patient with parathyroid carcinoma misdiagnosed as a parathyroid adenoma
      was reported. A solitary L4 vertebral metastasis, which was localized by
      technetium-99m-labelled methoxyisobutyl isonitrile ((99m)Tc-MIBI) single photon
      emission computed tomography (SPECT)/computed tomography (CT) fusing images, was
      successfully treated with percutaneous vertebroplasty (PVP) for the first time.
      PATIENT AND METHODS: A 53-year-old man with primary hyperparathyroidism and a
      palpable mass in the right neck was referred. A right unilateral
      parathyroidectomy was performed. A pathological diagnosis of parathyroid adenoma
      was made; however, hyperparathyroidism persisted with a serum calcium of 4.51
      mmol/L and a PTH of 3235 pg/mL. Early and delayed images of the (99m)Tc-MIBI
      whole-body scan revealed abnormal (99m)Tc-uptake in the lower abdomen. The
      delayed (99m)Tc-MIBI SPECT/CT fusion images found that the lower abnormal (99m)Tc
      MIBI uptake was located in the area of osteolytic destruction of the L4 vertebra.
      A bone metastasis from parathyroid carcinoma was diagnosed based on
      histopathological evaluation and immunohistochemical staining. PVP was performed
      to treat the osteolytic destruction of the L4 vertebra. The PTH level decreased
      to normal within 1 week after PVP. CONCLUSION: (99m)Tc-MIBI SPECT/CT scan may be
      a useful and suitable method by which to localize functioning distant metastases
      from the parathyroid cancer when serum PTH and calcium levels remain greatly
      elevated after parathyroidectomy. PVP may be an effective procedure in
      eliminating cancer cells, reducing serum PTH levels, preventing bone fractures,
      and improving the quality of life of patients.

PMID- 23861460
TI  - Improved insulin secretion following intrapancreatic UCB transplantation in
      patients with T2DM.
AB  - CONTEXT: Transplantation with stem cells has been reported as a potential
      treatment for diabetes. However, there are few reports examining transplantation
      with umbilical cord blood (UCB) in type 2 diabetes (T2DM). OBJECTIVE: The aim of
      the study was to evaluate the efficacy of intrapancreatic UCB transplantation in
      patients with T2DM. DESIGN AND SETTING: Three patients were enrolled in the
      study, which was performed in a hospital setting from 2010 to 2012, and the
      duration of follow-up was approximately 6 months. PATIENTS AND INTERVENTIONS: UCB
      cells were infused by microcatheter into the dorsal pancreatic artery in 3 T2DM
      patients with different diabetic histories. MAIN OUTCOME MEASURES: Blood glucose
      (including 72-h continuous blood glucose), C-peptide, hemoglobin A1c, the
      requirement for insulin, and transplant complications were monitored before and
      after transplantation. RESULTS: After the transplantation, C-peptide levels had
      increased in all of the patients. In addition, the 72-hour continuous blood
      glucose monitoring results obtained after transplantation revealed that levels
      were more stable than before transplantation for all of the patients (P < .05).
      In addition, the requirements of insulin were reduced in all patients after
      transplantation. CONCLUSION: UCB transplantation may be an approach that could
      somewhat improve C-peptide levels in patients with T2DM.

PMID- 23861461
TI  - Cortisol response to operative stress with anesthesia in healthy children.
AB  - BACKGROUND: Supraphysiological "stress dosing" is generally given to adrenally
      insufficient patients undergoing operative procedures and/or general anesthesia.
      However, the normal responses of cortisol to surgery are poorly documented,
      especially in small children. Recent studies in adults suggest that massive
      glucocorticoid dosing is not needed, especially in minimally invasive surgery.
      OBJECTIVE: We sought to characterize the normal cortisol secretion rate in
      healthy children undergoing minimally and moderately invasive urological
      procedures. DESIGN AND SETTING: This was a prospective observational study
      conducted at a tertiary referral center. PATIENTS: Thirty healthy children, ages
      5 months to 6 years, were studied undergoing elective urological procedures.
      METHODS: Procedures were performed by a single surgeon; anesthesia was by a
      standard protocol. Sera were obtained at 5 points: iv catheter placement,
      intubation, 50% completion of surgery, anesthesia reversal, and 1 hour
      postoperative. Cortisol and cortisone were quantitated by liquid chromatography
      tandem mass spectrometry. RESULTS: Group mean cortisol values ranged from 4.21 to
      5.71 MUg/dL across the 5 time points; none of these mean values differed
      significantly (P < .05). There were no differences according to age, time of
      procedure, caudal anesthesia, and moderate vs minimally invasive procedures; 3
      patients had higher values. There was a modest diminution in cortisone across the
      5 time points. CONCLUSIONS: Minimal and moderately invasive urological procedures
      do not result in a cortisol stress response in healthy children. Peak cortisol
      levels were seen 1 hour postoperatively. These data suggest that current
      guidelines for stress dosing in adrenally insufficient patients substantially
      exceed physiological requirements during minimally invasive procedures.

PMID- 23861462
TI  - Variants in SULT2A1 affect the DHEA sulphate to DHEA ratio in patients with
      polycystic ovary syndrome but not the hyperandrogenic phenotype.
AB  - CONTEXT: Because of the elevated dehydroepiandrosterone sulfate (DHEAS) levels in
      polycystic ovary syndrome (PCOS) and the heritability of DHEAS serum levels,
      genes encoding the enzymes that control the sulfation of dehydroepiandrosterone
      (DHEA) to DHEAS and vice versa are obvious candidate genes to explain part of the
      heritability of PCOS. OBJECTIVE: The objective of the study was to determine the
      role of genetic variants in sulfotransferase (SULT2A1), 3-phosphoadenosine 5
      phosphosulfate synthase isoform 2 (PAPSS2), and steroid sulfatase (STS) in PCOS
      and in hormone levels related to the hyperandrogenic phenotype of PCOS. DESIGN:
      This was a candidate-gene study. PATIENTS: The discovery set consisted of 582
      patients and 2017 controls. MAIN OUTCOME MEASURES: A pruned subset of 28 single
      nucleotide polymorphisms (SNPs) in SULT2A1, PAPSS2, and STS was generated based
      on pairwise genotypic correlation. Association with PCOS was tested, and we
      studied whether the SNPs modulate DHEAS levels, DHEA levels, and their ratio in
      PCOS. Significant SNPs were replicated in an independent sample of patients.
      RESULTS: None of the SNPs in SULT2A1, PAPSS2, and STS constituted risk alleles
      for PCOS. SNP rs2910397 in SULT2A1 decreased the DHEAS to DHEA ratio in PCOS by
      5% in the discovery sample. Meta-analysis of discovery and replication sample
      resulted in a combined effect of -0.095 (P = .027). However, carrying the minor T
      allele did not contribute to differences in the hyperandrogenic phenotype,
      including the levels of T and androstenedione, of PCOS patients. CONCLUSIONS:
      Genetic variants in SULT2A1, PAPSS2, and STS do not predispose to PCOS. Although
      a variant in SULT2A1 decreased the DHEAS to DHEA ratio, no changes in other
      androgenic hormone levels were observed.

PMID- 23861463
TI  - Medullary thyroid cancer secreting carbohydrate antigen 19-9 (Ca 19-9): a fatal
      case report.
AB  - BACKGROUND: During follow-up for patients with medullary thyroid cancer (MTC),
      the levels of serum calcitonin and carcinoembryonic antigen are important, and
      the doubling time of these biomarkers significantly correlates with disease
      progression. Other antigens are present in tumor tissue and the sera of patients
      with MTC, but there are scarce published data on the serum levels of carbohydrate
      antigen 19-9 (Ca 19-9), a tumor marker primarily used for the diagnosis and
      follow-up of pancreatic and gastrointestinal neoplasias. Recently, the case of a
      56-year-old woman with multiple endocrine neoplasia type 2B with high serum
      levels of Ca 19-9 was reported; this patient experienced rapid disease
      progression that led to her death. CASE PRESENTATION: A 28-year-old man was
      referred to the Department of Endocrinology of the University Hospital of Pisa
      with suspected MTC with laterocervical lymph node metastasis, a single liver
      lesion (10 mm), several bone metastases, and bilateral pheochromocytomas. RET
      genetic testing revealed a germline Cys634Arg mutation. During the
      hospitalization, the carcinoembryonic antigen and Ca 19-9 levels increased while
      the calcitonin concentration remained stable; despite the apparent stability of
      the lesions, the condition of the patient worsened rapidly and resulted in death.
      CONCLUSIONS: High levels of serum Ca 19-9 could be considered a marker of the
      dedifferentiation of MTC and disease aggressiveness, but additional data on the
      association between Ca 19-9 and advanced MTC are required to confirm this
      hypothesis.

PMID- 23861465
TI  - Bypassing the emergency department and time to reperfusion in patients with
      prehospital ST-segment-elevation: findings from the reperfusion in acute
      myocardial infarction in Carolina Emergency Departments project.
AB  - BACKGROUND: Among patients identified prehospital with ST-segment-elevation
      myocardial infarction, emergency medical service transport from the field
      directly to the catheterization laboratory, thereby bypassing the emergency
      department (ED), may shorten time to reperfusion. METHODS AND RESULTS: We studied
      1687 patients identified prehospital with ST-segment-elevation myocardial
      infarction from the Reperfusion in Acute Myocardial Infarction in Carolina
      Emergency Departments (RACE) project, transported via emergency medical service
      directly to 21 North Carolina hospitals for primary percutaneous coronary
      intervention between July 2008 and December 2009. Treatment time intervals were
      compared between patients evaluated in the ED (ED evaluation) and those
      transported directly to the catheterization laboratory (ED bypass). Emergency
      medical service transported 1401 (83.0%) patients to the ED, whereas the ED was
      bypassed for 286 (17.0%) patients. Overall, first medical contact to device
      activation within 90 minutes was achieved in 913 (54.1%) patients. Among patients
      evaluated in the ED, median time (25th-75th percentiles) from ED arrival to
      catheterization laboratory arrival was 30 (20-41) minutes. First medical contact
      to device activation occurred faster (75 [59-93] versus 90 [76-109] minutes;
      P<0.001) and was more frequently achieved within 90 minutes (74.1% versus 50.1%;
      P<0.001) among ED bypass patients. CONCLUSIONS: Among patients identified
      prehospital with ST-segment-elevation myocardial infarction and transported
      directly to a percutaneous coronary intervention hospital, only 1 in 2 achieve
      device activation within 90 minutes. A median of 30 minutes is spent in the ED,
      contributing significantly to the failure to achieve timely reperfusion. The
      strategy to bypass the ED is used infrequently and represents a potential
      opportunity to improve reperfusion times.

PMID- 23861464
TI  - SF3B1 mutations are associated with alternative splicing in uveal melanoma.
AB  - Uveal melanoma, the most common eye malignancy, causes severe visual morbidity
      and is fatal in approximately 50% of patients. Primary uveal melanoma can be
      cured by surgery or radiotherapy, but the metastatic disease is treatment
      refractory. To understand comprehensively uveal melanoma genetics, we conducted
      single-nucleotide polymorphism arrays and whole-genome sequencing on 12 primary
      uveal melanomas. We observed only approximately 2,000 predicted somatic single
      nucleotide variants per tumor and low levels of aneuploidy. We did not observe an
      ultraviolet radiation DNA damage signature, but identified SF3B1 mutations in
      three samples and a further 15 mutations in an extension cohort of 105 samples.
      SF3B1 mutations were associated with good prognosis and were rarely coincident
      with BAP1 mutations. SF3B1 encodes a component of the spliceosome, and RNA
      sequencing revealed that SF3B1 mutations were associated with differential
      alternative splicing of protein coding genes, including ABCC5 and UQCC, and of
      the long noncoding RNA CRNDE. SIGNIFICANCE: Our data show that despite its dismal
      prognosis, uveal melanoma is a relatively simple genetic disease characterized by
      recurrent chromosomal losses and gains and a low mutational burden. We show that
      SF3B1 is recurrently mutated in uveal melanoma, and the mutations are associated
      with aberrant alternative splicing.

PMID- 23861467
TI  - Cost of renal replacement therapy.

PMID- 23861466
TI  - Is genetic rescue of cystinosis an achievable treatment goal?
AB  - Cystinosis is an autosomal recessive metabolic disease that belongs to the family
      of lysosomal storage disorders. The defective gene is CTNS, which encodes the
      lysosomal cystine transporter, cystinosin. Cystine accumulates in all tissues and
      leads to organ damage including end-stage renal disease. In this review, we
      outline the studies that support that genetic rescue of cystinosis could be an
      achievable goal, even though cystinosis is a multi-compartmental disease and
      cystinosin an intracellular transmembrane protein. Using the mouse model of
      cystinosis, the Ctns(-/-) mice, we showed that transplanted hematopoietic stem
      cells (HSCs) were able to act as vehicles for the delivery of a functional Ctns
      gene to the different organs and led to the significant decrease of the tissue
      cystine content and tissue preservation. Ex vivo gene-modified Ctns(-/-) HSC
      transplantation using a lentiviral vector containing CTNS complementary DNA
      (cDNA) was also successful in the Ctns(-/-) mice and built the foundations for a
      clinical trial for autologous HSC transplantation for cystinosis. The capacity of
      HSCs for rescuing non-hematopoietic disease is controversial, and new insights
      into regenerative medicine could be gained from unraveling the underlying
      mechanism of action. 

PMID- 23861468
TI  - Longer interdialytic interval and cause-specific hospitalization in children
      receiving chronic dialysis.
AB  - BACKGROUND: Previous studies have demonstrated a relationship between longer
      interdialytic intervals and hospitalization for cardiovascular causes in adults
      maintained on hemodialysis (HD). This association has not been previously
      demonstrated in children. We hypothesized that the risk of hospitalization for
      hypertension (HTN), fluid overload or electrolyte abnormalities would be
      increased on the days following a longer interdialytic interval in children.
      METHODS: We queried the Pediatric Hospital Information System for all admissions
      of patients with chronic kidney disease stage V or V-D who received dialysis
      during the hospitalization. Admissions were divided into two categories:
      admissions for HTN, fluid overload or electrolyte abnormalities and admissions
      for all other causes. We assumed that HD patients did not receive dialysis on
      weekends, and therefore any admission on Monday occurred following a longer
      interval from the last dialysis. We assumed that all peritoneal dialysis (PD)
      patients received dialysis on a daily basis. We used mixed effects logistic
      regression, clustering by patient within each hospital, to assess the increased
      odds for cause-specific admission on Monday versus other days of the week. We
      stratified the analysis by dialysis modality, HD or PD. RESULTS: Among HD
      patients, the odds ratio of admission for HTN, fluid overload or electrolyte
      abnormalities was 2.6 (95% CI = 1.4-4.7, P = 0.003) if the admission occurred on
      a Monday versus other days of the week. The odds of cause-specific admission
      among PD patients was not significantly different on Monday compared with other
      days of the week (95% CI =0.5-1.3, P = 0.8). CONCLUSION: Children receiving
      chronic HD are more likely to be hospitalized for HTN, fluid overload or
      electrolyte abnormalities following a longer interdialytic interval. Changes to
      the frequency of outpatient dialysis treatments may decrease admissions in this
      population and decrease resource utilization in this high-risk population.

PMID- 23861469
TI  - EPR oxygen images predict tumor control by a 50% tumor control radiation dose.
AB  - Clinical trials to ameliorate hypoxia as a strategy to relieve the radiation
      resistance it causes have prompted a need to assay the precise extent and
      location of hypoxia in tumors. Electron paramagnetic resonance oxygen imaging
      (EPR O2 imaging) provides a noninvasive means to address this need. To obtain a
      preclinical proof-of-principle that EPR O2 images could predict radiation
      control, we treated mouse tumors at or near doses required to achieve 50% control
      (TCD50). Mice with FSa fibrosarcoma or MCa4 carcinoma were subjected to EPR O2
      imaging and immediately radiated to a TCD50 or TCD50 +/- 10 Gy. Statistical
      analysis was permitted by collection of approximately 1,300 tumor pO2 image
      voxels, including the fraction of tumor voxels with pO2 less than 10 mm Hg
      (HF10). Tumors were followed for 90 days (FSa) or 120 days (MCa4) to determine
      local control or failure. HF10 obtained from EPR images showed statistically
      significant differences between tumors that were controlled by the TCD50 and
      those that were not controlled for both FSa and MCa4. Kaplan-Meier analysis of
      both types of tumors showed that approximately 90% of mildly hypoxic tumors were
      controlled (HF10%< 10%), and only 37% (FSA) and 23% (MCa4) tumors controlled if
      hypoxic. EPR pO2 image voxel distributions in these approximately 0.5 mL tumors
      provide a prediction of radiation curability independent of radiation dose. These
      data confirm the significance of EPR pO2 hypoxic fractions. The 90% control of
      low HF10 tumors argue that 0.5 mL subvolumes of tumors may be more sensitive to
      radiation and may need less radiation for high tumor control rates. Cancer Res;
      73(17); 5328-35. (c)2013 AACR. 

PMID- 23861470
TI  - Co-polysomy of chromosome 1q and 19p predicts worse prognosis in 1p/19q codeleted
      oligodendroglial tumors: FISH analysis of 148 consecutive cases.
AB  - BACKGROUND: This study aimed to evaluate the prognostic significance of co
      polsomy of chromosome 1q and 19p in 1p/19q codeleted oligodendroglial tumors
      (ODGs). METHODS: In a series of 148 ODGs with 1p/19q deletion, co-polysomy of 1q
      and 19p was detected by fluorescence in situ hybridization (FISH). Log-rank
      analysis and Cox regression methods were used to compare Kaplan-Meier plots and
      identify factors associated with worse prognosis. RESULTS: There were 104 (70.3%)
      low-grade ODGs and 44 (29.7%) high-grade ODGs. Co-polysomy was independently
      associated with shorter progression-free survival and overall survival in 1p/19q
      codeleted ODGs, irrespective of tumor grades. The odds ratio of without and with
      co-polysomy was 0.263 (95% confidence interval [CI], 0.089-0.771; P = .015) for
      progression-free survival and 0.213 (95% CI, 0.060-0.756; P = .017) for overall
      survival. Subgroup analysis confirmed this trend in both low-grade and high-grade
      ODGs, although the P value for high-grade ODGs was marginally significant.
      CONCLUSIONS: Co-polysomy of 1q and 19p could be used as a marker to independently
      predict worse prognoses and guide individual therapy in 1p/19q codeleted ODGs.

PMID- 23861478
TI  - Associations between tobacco control policy awareness, social acceptability of
      smoking and smoking cessation. Findings from the International Tobacco Control
      (ITC) Europe Surveys.
AB  - This study examined whether awareness of tobacco control policies was associated
      with social unacceptability of smoking and whether social unacceptability had an
      effect on smoking cessation in three European countries. Representative samples
      (n = 3865) of adult smokers in France, the Netherlands and Germany were used from
      two survey waves of the longitudinal International Tobacco Control Europe
      Surveys. Associations were examined of aspects of social unacceptability of
      smoking (i.e. feeling uncomfortable, important people disapproval and societal
      disapproval) with tobacco policy awareness (i.e. awareness of warning labels,
      anti-tobacco information and smoking restrictions at work) and smoking cessation.
      Only the positive association of awareness of anti-tobacco information with
      feeling uncomfortable about smoking was significant in each of the three
      countries. Important people disapproval predicted whether smokers attempted to
      quit, although this did not reach significance in the French and German samples
      in multivariate analyses. Our findings suggest that anti-tobacco information
      campaigns about the dangers of second-hand smoke in France and about smoking
      cessation in the Netherlands and Germany might have reduced the social
      acceptability of smoking in these countries. However, campaigns that influence
      the perceived disapproval of smoking by important people may be needed to
      ultimately increase attempts to quit smoking. 

PMID- 23861479
TI  - Barriers and facilitators to the promotion of healthy eating lifestyles among
      adolescents at school: the views of school health coordinators.
AB  - This study evaluates the perceptions of teachers in charge of coordinating health
      education in schools: the School Health Coordinators (SHCs). It addresses the
      success and barriers of the development and implementation regarding the first
      year of healthy eating programmes in their schools. This research is based on 16
      face-to-face semi-structured interviews with SHCs from Portuguese public schools
      offering from fifth to ninth grades. A thematic analysis was performed and themes
      were identified, taking into consideration similarities and differences among the
      participants' opinions. The results showed that the schools in this study often
      involved a set of separate healthy diet promotion activities with a low level of
      joint effort from all members of the school. Nevertheless, in Portugal, health
      education is based on the broad concept that school health promotion is
      compulsory for all schools. Two main barriers were identified in order to explain
      this divergence: structural and political idiosyncrasies among schools and the
      food environment inside and outside the schools. The results are discussed
      considering the wide range of factors influencing young people's eating
      behaviours and recommendations are made for the different agents interacting with
      them in order to promote appropriate eating habits. 

PMID- 23861480
TI  - An exploratory investigation amongst Australian mothers regarding pharmacies and
      opportunities for nutrition promotion.
AB  - The early years life-stage (1 year either side of childbirth) is an important
      period for preventive action focusing on optimizing nutritional health for
      mothers and babies. Community pharmacy is a much utilized, easily accessed
      setting for health promotion and exposure to the primary health care system. The
      literature suggests that there has been limited exploration of pharmacy
      utilization by mothers, particularly in the context of nutrition focused health
      promotion. This study aimed to explore mothers' expectations and experiences of
      pharmacy based health care and to explore mothers' attitudes and opinions
      regarding opportunities and scope for nutrition-related health promotion in
      pharmacy. Qualitative semi-structured telephone interviews were conducted amongst
      a purposive sample of 28 mothers from across Queensland, Australia. Interviews
      were transcribed and analysed thematically using an iterative approach.
      Participants as relatively frequent users of pharmacy services accessed pharmacy
      for medicines or product related concerns but expected information and health
      advice to be available. Opportunities for nutrition promotion in pharmacy,
      identified by participants, related primarily to addressing their personal needs
      for information, advice and support during this life-stage. Improving and
      reorienting pharmacy staff practices may contribute to more supportive guidance
      being provided to mothers in this setting. 

PMID- 23861481
TI  - Accessing sexual health information online: use, motivations and consequences for
      youth with different sexual orientations.
AB  - We examine reasons why youth of different sexual orientations look for sexual
      health information online, and what, if anything, they do with it. The Teen
      Health and Technology study involved online surveys of 5542 Internet users, ages
      13 through 18 in the United States. Searching for sexual health information
      online was reported frequently and varied significantly by sexual orientation:
      from 19% of heterosexual youth to 78% of gay/lesbian/queer youth. The most common
      reasons youth look for sexual health information is for privacy and curiosity.
      Sexual minority youth are more likely than heterosexual youth to report that they
      looked for information online because they did not have anyone to ask. Once youth
      have the information, no differences by sexual orientation were noted as to what
      they did with it. Instead, seeking out the information for privacy-related
      reasons and having no one to ask were related to taking some action on the
      information received. Findings indicate that online information is most valuable
      to those youth who lack alternatives. Care needs to be taken to help ensure that
      the sexual health information online is accurate and includes topics specific to
      sexual minority youth. 

PMID- 23861482
TI  - Alterations in the frequency of trinucleotide repeat dynamic mutations in
      offspring conceived through assisted reproductive technology.
AB  - STUDY QUESTION: How does the frequency of trinucleotide repeat dynamic mutations
      in offspring conceived through assisted reproductive technology (ART) compare
      with the frequency of these mutations in control offspring conceived from
      spontaneous pregnancies? SUMMARY ANSWER: There is a slight increase in dynamic
      mutation instability in offspring conceived through ART compared with the
      naturally conceived offspring. WHAT IS KNOWN ALREADY: There is evidence to
      suggest that ART can increase the risk of birth defects and karyotypic
      abnormalities. However, the accumulating evidence of an association between ART
      and de novo genetic aberrations is controversial. STUDY DESIGN, SIZE, DURATION: A
      prospective clinical observational study was performed on 246 families recruited
      from an in vitro fertilisation (IVF) centre at a tertiary-care, university
      affiliated teaching hospital from 2008 to 2012. The study included 147 ART
      families [75 IVF and 72 intracytoplasmic sperm injection (ICSI)] in the study
      group and 99 natural-conception families in the control group. PARTICIPANTS,
      SETTING, METHODS: Parental, umbilical cord and infant peripheral blood samples
      were collected, and the trinucleotide repeats of the ATN1, AR, ATXN1, ATXN3,
      Huntington, DMPK and FMR-1 genes were investigated between the generations; these
      genes were chosen due to their ability to undergo dynamic mutation. The
      frequencies and sizes of the mutational repeats, as well as the intergenerational
      instability, were measured. MAIN RESULTS AND THE ROLE OF CHANCE: In 2466
      transmissions identified in the ART offspring, 2.11% (n = 52/2466) of the alleles
      were unstable upon transmission, while in the control group offspring, the
      frequency of dynamic mutation was 0.77% (n = 10/1300); this difference was
      statistically significant (P < 0.01). The unstable transmission alleles were
      detected in 32 (2.48%) of the 1288 alleles from the IVF offspring and in 20
      (1.70%) of the 1178 alleles from the ICSI offspring; both of these frequencies
      were significantly different from that of naturally conceived offspring (0.77%)
      (P < 0.01 and P < 0.05, respectively). However, there were no significant
      differences in the sizes of the mutational repeats or in the rates of expansion
      or contraction among the three groups (P > 0.05). The repeat copy numbers of the
      examined genes were found to be within the normal ranges in all parents and
      infants. LIMITATIONS, REASONS FOR CAUTION: One strength of our study is the
      relatively large sample size; we were able to detect mutations in seven common
      dynamic genes, and this large sample size allowed us to detect unstable alleles.
      Although we observed a clear alteration in the frequency of dynamic mutation in
      the ART offspring compared with controls, further studies are urgently needed to
      confirm this observation and determine the cause of this phenomenon. WIDER
      IMPLICATIONS OF THE FINDINGS: DNA microsatellite analysis provides an important
      tool to assess genomic instability. In this study, we report an association
      between ART and the frequency of dynamic mutation. The instability could be a
      reflection of the core infertility problem, the controlled ovarian
      hyperstimulation and/or the in vitro culture conditions.

PMID- 23861483
TI  - Hospital strategies associated with 30-day readmission rates for patients with
      heart failure.
AB  - BACKGROUND: Reducing hospital readmission rates is a national priority; however,
      evidence about hospital strategies that are associated with lower readmission
      rates is limited. We sought to identify hospital strategies that were associated
      with lower readmission rates for patients with heart failure. METHODS AND
      RESULTS: Using data from a Web-based survey of hospitals participating in
      national quality initiatives to reduce readmission (n=599; 91% response rate)
      during 2010-2011, we constructed a multivariable linear regression model,
      weighted by hospital volume, to determine strategies independently associated
      with risk-standardized 30-day readmission rates (RSRRs) adjusted for hospital
      teaching status, geographic location, and number of staffed beds. Strategies that
      were associated with lower hospital RSRRs included the following: (1) partnering
      with community physicians or physician groups to reduce readmission (0.33%
      percentage point lower RSRRs; P=0.017), (2) partnering with local hospitals to
      reduce readmissions (0.34 percentage point; P=0.020), (3) having nurses
      responsible for medication reconciliation (0.18 percentage point; P=0.002), (4)
      arranging follow-up appointments before discharge (0.19 percentage point;
      P=0.037), (5) having a process in place to send all discharge paper or electronic
      summaries directly to the patient's primary physician (0.21 percentage point;
      P=0.004), and (6) assigning staff to follow up on test results that return after
      the patient is discharged (0.26 percentage point; P=0.049). Although
      statistically significant, the magnitude of the effects was modest with
      individual strategies associated with less than half a percentage point reduction
      in RSRRs; however, hospitals that implemented more strategies had significantly
      lower RSRRs (reduction of 0.34 percentage point for each additional strategy).
      CONCLUSIONS: Several strategies were associated with lower hospital RSRRs for
      patients with heart failure.

PMID- 23861485
TI  - Cardiac insulin-resistance and decreased mitochondrial energy production precede
      the development of systolic heart failure after pressure-overload hypertrophy.
AB  - BACKGROUND: Cardiac hypertrophy is accompanied by significant alterations in
      energy metabolism. Whether these changes in energy metabolism precede and
      contribute to the development of heart failure in the hypertrophied heart is not
      clear. METHODS AND RESULTS: Mice were subjected to cardiac hypertrophy secondary
      to pressure-overload as a result of an abdominal aortic constriction (AAC). The
      rates of energy substrate metabolism were assessed in isolated working hearts
      obtained 1, 2, and 3 weeks after AAC. Mice subjected to AAC demonstrated a
      progressive development of cardiac hypertrophy. In vivo assessment of cardiac
      function (via echocardiography) demonstrated diastolic dysfunction by 2 weeks
      (20% increase in E/E'), and systolic dysfunction by 3 weeks (16% decrease in %
      ejection fraction). Marked cardiac insulin-resistance by 2 weeks post-AAC was
      evidenced by a significant decrease in insulin-stimulated rates of glycolysis and
      glucose oxidation, and plasma membrane translocation of glucose transporter 4.
      Overall ATP production rates were decreased at 2 and 3 weeks post-AAC (by 37% and
      47%, respectively) because of a reduction in mitochondrial oxidation of glucose,
      lactate, and fatty acids that was not accompanied by an increase in myocardial
      glycolysis rates. Reduced mitochondrial complex V activity was evident at 3 weeks
      post-AAC, concomitant with a reduction in the ratio of phosphocreatine to ATP.
      CONCLUSIONS: The development of cardiac insulin-resistance and decreased
      mitochondrial oxidative metabolism are early metabolic changes in the development
      of cardiac hypertrophy, which create an energy deficit that may contribute to the
      progression from hypertrophy to heart failure.

PMID- 23861484
TI  - Ceruloplasmin and heart failure in the Atherosclerosis Risk in Communities study.
AB  - BACKGROUND: Ceruloplasmin (Cp) decreases nitric oxide bioavailability in blood
      and has been associated with cardiovascular disease (CVD) in clinical studies. We
      assessed the associations between Cp and incident heart failure (HF), death, and
      CVD in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS:
      Cp was measured at ARIC visit 4 (1996-1998). We studied 9240 individuals without
      HF or CVD at ARIC visit 4 and followed them for a mean of 10.5 years. Genome-wide
      association study was performed to identify genetic determinants of Cp levels and
      evaluate their association with incident HF in ARIC participants. Cp levels
      (mean+/-SD) were higher in women versus men (335+/-79 versus 258+/-44 mg/L;
      P<0.0001), women on versus not on hormone-replacement therapy (398+/-89 versus
      291+/-60 mg/L; P<0.0001), and African Americans versus whites (299+/-63 versus
      293+/-74 mg/L; P=0.0005). After adjusting for traditional risk factors, high
      sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and
      high-sensitivity cardiac troponin T, higher levels of Cp were associated with HF
      (hazard ratio, 1.44; 95% confidence interval, 1.13-1.83) and mortality (hazard
      ratio, 1.38; 95% confidence interval, 1.11-1.63). A locus on the ceruloplasmin
      gene on chromosome 3 was significantly associated with Cp levels (normal 295.56+/
      77.60 mg/L; heterozygote 316.72+/-88.02 mg/L; homozygote 331.04+/-85.40 mg/L;
      P=8.3*10(-13)) but not with incident HF. After adjustment for traditional risk
      factors, Cp levels were also weekly associated with CVD. CONCLUSIONS: Cp was
      associated with incident HF, mortality, and CVD in the ARIC population. A single
      locus on chromosome 3 was associated with Cp levels but not with HF.

PMID- 23861486
TI  - Angiotensin II-converting enzyme inhibition improves survival, ventricular
      remodeling, and myocardial energetics in experimental aortic regurgitation.
AB  - BACKGROUND: Aortic valve regurgitation (AR) is a volume-overload disease causing
      severe eccentric left ventricular (LV) hypertrophy and eventually heart failure.
      There is currently no approved drug to treat patients with AR. Many vasodilators
      including angiotensin-converting enzyme inhibitors have been evaluated in
      clinical trials, but although some results were promising, others were
      inconclusive. Overall, no drug has yet been able to improve clinical outcome in
      AR and the controversy remains. We have previously shown in an animal model that
      captopril (Cpt) reduced LV hypertrophy and protected LV systolic function, but we
      had not evaluated the clinical outcome. This protocol was designed to evaluate
      the effects of a long-term Cpt treatment on survival in the same animal model of
      severe aortic valve regurgitation. METHODS AND RESULTS: Forty Wistar rats with AR
      were treated or untreated with Cpt (1 g/L in drinking water) for a period of 7
      months to evaluate survival, myocardial remodeling, and function by
      echocardiography as well as myocardial metabolism by u positron emission
      tomography scan. Survival was significantly improved in Cpt-treated animals with
      a survival benefit visible as soon as after 4 months of treatment. Cpt reduced LV
      dilatation and LV hypertrophy. It also significantly improved the myocardial
      metabolic profile by restoring the level of fatty acids metabolic enzymes and
      use. CONCLUSIONS: In a controlled animal model of pure severe aortic valve
      regurgitation, Cpt treatment reduced LV remodeling and LV hypertrophy and
      improved myocardial metabolic profile and survival. These results support the
      need to reevaluate the role of angiotensin-converting enzyme inhibitors in humans
      with AR in a large, carefully designed prospective clinical trial.

PMID- 23861487
TI  - Gravitational lensing.

PMID- 23861490
TI  - Nuclear dynamics in a fungal chimera.
AB  - A fungal colony is a syncytium composed of a branched and interconnected network
      of cells. Chimerism endows colonies with increased virulence and ability to
      exploit nutritionally complex substrates. Moreover, chimera formation may be a
      driver for diversification at the species level by allowing lateral gene transfer
      between strains that are too distantly related to hybridize sexually. However,
      the processes by which genomic diversity develops and is maintained within a
      single colony are little understood. In particular, both theory and experiments
      show that genetically diverse colonies may be unstable and spontaneously
      segregate into genetically homogenous sectors. By directly measuring patterns of
      nuclear movement in the model ascomycete fungus Neurospora crassa, we show that
      genetic diversity is maintained by complex mixing flows of nuclei at all length
      scales within the hyphal network. Mathematical modeling and experiments in a
      morphological mutant reveal some of the exquisite hydraulic engineering necessary
      to create the mixing flows. In addition to illuminating multinucleate and
      multigenomic lifestyles, the adaptation of a hyphal network for mixing nuclear
      material provides a previously unexamined organizing principle for understanding
      morphological diversity in the more-than-a-million species of filamentous fungi. 

PMID- 23861489
TI  - Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening.
AB  - Voltage-gated ion channels generate dynamic ionic currents that are vital to the
      physiological functions of many tissues. These proteins contain separate voltage
      sensing domains, which detect changes in transmembrane voltage, and pore domains,
      which conduct ions. Coupling of voltage sensing and pore opening is critical to
      the channel function and has been modeled as a protein-protein interaction
      between the two domains. Here, we show that coupling in Kv7.1 channels requires
      the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). We found that voltage
      sensing domain activation failed to open the pore in the absence of PIP2. This
      result is due to loss of coupling because PIP2 was also required for pore opening
      to affect voltage-sensing domain activation. We identified a critical site for
      PIP2-dependent coupling at the interface between the voltage-sensing domain and
      the pore domain. This site is actually a conserved lipid-binding site among
      different K(+) channels, suggesting that lipids play an important role in
      coupling in many ion channels. 

PMID- 23861491
TI  - Lariat sequencing in a unicellular yeast identifies regulated alternative
      splicing of exons that are evolutionarily conserved with humans.
AB  - Alternative splicing is a potent regulator of gene expression that vastly
      increases proteomic diversity in multicellular eukaryotes and is associated with
      organismal complexity. Although alternative splicing is widespread in
      vertebrates, little is known about the evolutionary origins of this process, in
      part because of the absence of phylogenetically conserved events that cross major
      eukaryotic clades. Here we describe a lariat-sequencing approach, which offers
      high sensitivity for detecting splicing events, and its application to the
      unicellular fungus, Schizosaccharomyces pombe, an organism that shares many of
      the hallmarks of alternative splicing in mammalian systems but for which no
      previous examples of exon-skipping had been demonstrated. Over 200 previously
      unannotated splicing events were identified, including examples of regulated
      alternative splicing. Remarkably, an evolutionary analysis of four of the exons
      identified here as subject to skipping in S. pombe reveals high sequence
      conservation and perfect length conservation with their homologs in scores of
      plants, animals, and fungi. Moreover, alternative splicing of two of these exons
      have been documented in multiple vertebrate organisms, making these the first
      demonstrations of identical alternative-splicing patterns in species that are
      separated by over 1 billion y of evolution. 

PMID- 23861492
TI  - Patterns of new versus recycled primary production in the terrestrial biosphere.
AB  - Nitrogen (N) and phosphorus (P) availability regulate plant productivity
      throughout the terrestrial biosphere, influencing the patterns and magnitude of
      net primary production (NPP) by land plants both now and into the future. These
      nutrients enter ecosystems via geologic and atmospheric pathways and are recycled
      to varying degrees through the plant-soil-microbe system via organic matter decay
      processes. However, the proportion of global NPP that can be attributed to new
      nutrient inputs versus recycled nutrients is unresolved, as are the large-scale
      patterns of variation across terrestrial ecosystems. Here, we combined satellite
      imagery, biogeochemical modeling, and empirical observations to identify
      previously unrecognized patterns of new versus recycled nutrient (N and P)
      productivity on land. Our analysis points to tropical forests as a hotspot of new
      NPP fueled by new N (accounting for 45% of total new NPP globally), much higher
      than previous estimates from temperate and high-latitude regions. The large
      fraction of tropical forest NPP resulting from new N is driven by the high
      capacity for N fixation, although this varies considerably within this diverse
      biome; N deposition explains a much smaller proportion of new NPP. By contrast,
      the contribution of new N to primary productivity is lower outside the tropics,
      and worldwide, new P inputs are uniformly low relative to plant demands. These
      results imply that new N inputs have the greatest capacity to fuel additional NPP
      by terrestrial plants, whereas low P availability may ultimately constrain NPP
      across much of the terrestrial biosphere. 

PMID- 23861493
TI  - Generation of functionally competent and durable engineered blood vessels from
      human induced pluripotent stem cells.
AB  - Efficient generation of competent vasculogenic cells is a critical challenge of
      human induced pluripotent stem (hiPS) cell-based regenerative medicine.
      Biologically relevant systems to assess functionality of the engineered vessels
      in vivo are equally important for such development. Here, we report a unique
      approach for the derivation of endothelial precursor cells from hiPS cells using
      a triple combination of selection markers--CD34, neuropilin 1, and human kinase
      insert domain-containing receptor--and an efficient 2D culture system for hiPS
      cell-derived endothelial precursor cell expansion. With these methods, we
      successfully generated endothelial cells (ECs) from hiPS cells obtained from
      healthy donors and formed stable functional blood vessels in vivo, lasting for
      280 d in mice. In addition, we developed an approach to generate mesenchymal
      precursor cells (MPCs) from hiPS cells in parallel. Moreover, we successfully
      generated functional blood vessels in vivo using these ECs and MPCs derived from
      the same hiPS cell line. These data provide proof of the principle that
      autologous hiPS cell-derived vascular precursors can be used for in vivo
      applications, once safety and immunological issues of hiPS-based cellular therapy
      have been resolved. Additionally, the durability of hiPS-derived blood vessels in
      vivo demonstrates a potential translation of this approach in long-term
      vascularization for tissue engineering and treatment of vascular diseases. Of
      note, we have also successfully generated ECs and MPCs from type 1 diabetic
      patient-derived hiPS cell lines and use them to generate blood vessels in vivo,
      which is an important milestone toward clinical translation of this approach.

PMID- 23861494
TI  - Induction of human cardiomyocyte-like cells from fibroblasts by defined factors.
AB  - Heart disease remains a leading cause of death worldwide. Owing to the limited
      regenerative capacity of heart tissue, cardiac regenerative therapy has emerged
      as an attractive approach. Direct reprogramming of human cardiac fibroblasts
      (HCFs) into cardiomyocytes may hold great potential for this purpose. We reported
      previously that induced cardiomyocyte-like cells (iCMs) can be directly generated
      from mouse cardiac fibroblasts in vitro and vivo by transduction of three
      transcription factors: Gata4, Mef2c, and Tbx5, collectively termed GMT. In the
      present study, we sought to determine whether human fibroblasts also could be
      converted to iCMs by defined factors. Our initial finding that GMT was not
      sufficient for cardiac induction in HCFs prompted us to screen for additional
      factors to promote cardiac reprogramming by analyzing multiple cardiac-specific
      gene induction with quantitative RT-PCR. The addition of Mesp1 and Myocd to GMT
      up-regulated a broader spectrum of cardiac genes in HCFs more efficiently
      compared with GMT alone. The HCFs and human dermal fibroblasts transduced with
      GMT, Mesp1, and Myocd (GMTMM) changed the cell morphology from a spindle shape to
      a rod-like or polygonal shape, expressed multiple cardiac-specific proteins,
      increased a broad range of cardiac genes and concomitantly suppressed fibroblast
      genes, and exhibited spontaneous Ca(2+) oscillations. Moreover, the cells matured
      to exhibit action potentials and contract synchronously in coculture with murine
      cardiomyocytes. A 5-ethynyl-2'-deoxyuridine assay revealed that the iCMs thus
      generated do not pass through a mitotic cell state. These findings demonstrate
      that human fibroblasts can be directly converted to iCMs by defined factors,
      which may facilitate future applications in regenerative medicine. 

PMID- 23861495
TI  - A cantilever-free approach to dot-matrix nanoprinting.
AB  - Scanning probe lithography (SPL) is a promising candidate approach for desktop
      nanofabrication, but trade-offs in throughput, cost, and resolution have limited
      its application. The recent development of cantilever-free scanning probe arrays
      has allowed researchers to define nanoscale patterns in a low-cost and high
      resolution format, but with the limitation that these are duplication tools where
      each probe in the array creates a copy of a single pattern. Here, we report a
      cantilever-free SPL architecture that can generate 100 nanometer-scale molecular
      features using a 2D array of independently actuated probes. To physically actuate
      a probe, local heating is used to thermally expand the elastomeric film beneath a
      single probe, bringing it into contact with the patterning surface. Not only is
      this architecture simple and scalable, but it addresses fundamental limitations
      of 2D SPL by allowing one to compensate for unavoidable imperfections in the
      system. This cantilever-free dot-matrix nanoprinting will enable the construction
      of surfaces with chemical functionality that is tuned across the nano- and
      macroscales. 

PMID- 23861496
TI  - Crystal structure of a GroEL-ADP complex in the relaxed allosteric state at 2.7 A
      resolution.
AB  - The chaperonin proteins GroEL and GroES are cellular nanomachines driven by the
      hydrolysis of ATP that facilitate the folding of structurally diverse substrate
      proteins. In response to ligand binding, the subunits of a ring cycle in a
      concerted manner through a series of allosteric states (T, R, and R"), enabling
      work to be performed on the substrate protein. Removing two salt bridges that
      ordinarily break during the allosteric transitions of the WT permitted the
      structure of GroEL-ADP in the R state to be solved to 2.7 A resolution. Whereas
      the equatorial domain displays almost perfect sevenfold symmetry, the apical
      domains, to which substrate proteins bind, and to a lesser extent, the
      intermediate domains display a remarkable asymmetry. Freed of intersubunit
      contacts, the apical domain of each subunit adopts a different conformation,
      suggesting a flexibility that permits interaction with diverse substrate
      proteins. This result contrasts with a previous cryo-EM study of a related
      allosteric ATP-bound state at lower resolution. After artificially imposing
      sevenfold symmetry it was concluded that a GroEL ring in the R-ATP state existed
      in six homogeneous but slightly different states. By imposing sevenfold symmetry
      on each of the subunits of the crystal structure of GroEL-ADP, we showed that the
      synthetic rings of (X-ray) GroEL-ADP and (cryo-EM) GroEL-ATP are structurally
      closely related. A deterministic model, the click stop mechanism, that implied
      temporal transitions between these states was proposed. Here, however, these
      conformational states are shown to exist as a structurally heterogeneous ensemble
      within a single ring. 

PMID- 23861497
TI  - Is adolescent endometriosis a progressive disease that needs to be diagnosed and
      treated?

PMID- 23861498
TI  - Rupture of the left atrial roof due to blunt trauma.
AB  - Cardiac rupture after blunt trauma is rare and associated with high mortality.
      The anatomic pattern of blunt cardiac rupture has been demonstrated with the
      right cardiac chambers more frequently affected than the left. Furthermore, left
      atrial injury is usually restricted to the atrial appendage and the pulmonary
      vein-atrial junction. Herein, we report the first case of a 61-year old man with
      a rupture of the left atrial roof after blunt trauma with minimal thoracic
      injury. 

PMID- 23861500
TI  - Emerging concepts in the management of acute retinal necrosis.
AB  - Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon
      condition caused by infection of the retina by one of the herpes family of
      viruses, most typically varicella zoster virus or herpes simplex virus and less
      commonly cytomegalovirus. Clinical diagnosis can be challenging and is often
      aided by PCR-based analysis of ocular fluids. Treatment typically involves
      extended use of one or more antiviral agents. Long term retinal detachment risk
      is high. We review the literature on ARN and present an approach to the diagnosis
      and management of this serious condition.

PMID- 23861501
TI  - Opium.

PMID- 23861502
TI  - Ectopic and serum lipid levels are positively associated with bone marrow fat in
      obesity.
AB  - PURPOSE: To investigate the associations between ectopic and serum lipid levels
      and bone marrow fat, as a marker of stem cell differentiation, in young obese men
      and women, with the hypothesis that ectopic and serum lipid levels would be
      positively associated with bone marrow fat. MATERIALS AND METHODS: The study was
      institutional review board approved and complied with HIPAA guidelines. Written
      informed consent was obtained. The study group comprised 106 healthy young men
      and women (mean age, 33.7 years +/- 6.8 [standard deviation]; range, 19-45 years;
      mean body mass index (BMI), 33.1 kg/m(2) +/- 7.1; range, 18.1-48.8 kg/m(2)) who
      underwent hydrogen 1((1)H) magnetic resonance (MR) spectroscopy by using a point
      resolved spatially localized spectroscopy sequence at 3.0 T of L4 for bone marrow
      fat content, of soleus muscle for intramyocellular lipids (IMCL), and liver for
      intrahepatic lipids (IHL), serum cholesterol level, serum triglyceride level, and
      measures of insulin resistance (IR). Exercise status was assessed with the
      Paffenbarger activity questionnaire. RESULTS: There was a positive correlation
      between bone marrow fat and IHL (r = 0.21, P = .048), IMCL (r = 0.27, P = .02),
      and serum triglyceride level (r = 0.33, P = .001), independent of BMI, age, IR,
      and exercise status (P < .05). High-density lipoprotein cholesterol levels were
      inversely associated with bone marrow fat content, independent of BMI, age, IR,
      and exercise status (r = -0.21, P = .019). CONCLUSION: Results of this study
      suggest that ectopic and serum lipid levels are positively associated with bone
      marrow fat in obese men and women.

PMID- 23861503
TI  - Identifying heart failure hospitalizations: can an automated algorithm become a
      gold standard?

PMID- 23861504
TI  - Mitral regurgitation: has another magic bullet bitten the dust?

PMID- 23861506
TI  - Is there a rationale for antiplatelet therapy in acute heart failure?

PMID- 23861507
TI  - Percutaneous intervention for recurrent aortic insufficiency in a patient with a
      left ventricular assist device and a centrally oversewn aortic valve.

PMID- 23861508
TI  - Apical sparing of longitudinal strain, left ventricular rotational abnormalities,
      and short-axis dysfunction in primary hyperoxaluria type 1.

PMID- 23861505
TI  - Xanthine oxidase inhibition for hyperuricemic heart failure patients: design and
      rationale of the EXACT-HF study.

PMID- 23861510
TI  - Letter by Maini regarding article, "percutaneous left-ventricular support with
      the impella-2.5-assist device in acute cardiogenic shock: results of the impella
      EUROSHOCK-registry".

PMID- 23861511
TI  - Letter by Januzzi regarding article, "galectin-3 and cardiac function in
      survivors of acute myocardial infarction".

PMID- 23861513
TI  - Antithrombotic therapy for patients with atrial fibrillation and atherothrombotic
      vascular disease: striking the right balance between efficacy and safety.

PMID- 23861512
TI  - Use and associated risks of concomitant aspirin therapy with oral anticoagulation
      in patients with atrial fibrillation: insights from the Outcomes Registry for
      Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry.
AB  - BACKGROUND: The role of concomitant aspirin (ASA) therapy in patients with atrial
      fibrillation (AF) receiving oral anticoagulation (OAC) is unclear. We assessed
      concomitant ASA use and its association with clinical outcomes among AF patients
      treated with OAC. METHODS AND RESULTS: The Outcomes Registry for Better Informed
      Treatment of Atrial Fibrillation (ORBIT-AF) registry enrolled 10 126 AF patients
      from 176 US practices from June 2010 through August 2011. The study population
      was limited to those on OAC (n=7347). Hierarchical multivariable logistic
      regression models were used to assess factors associated with concomitant ASA
      therapy. Primary outcomes were 6-month bleeding, hospitalization, ischemic
      events, and mortality. Overall, 35% of AF patients (n=2543) on OAC also received
      ASA (OAC+ASA). Patients receiving OAC+ASA were more likely to be male (66% versus
      53%; P<0.0001) and had more comorbid illness than those on OAC alone. More than
      one third of patients (39%) receiving OAC+ASA did not have a history of
      atherosclerotic disease, yet 17% had elevated Anticoagulation and Risk Factors in
      Atrial Fibrillation (ATRIA) bleeding risk scores (>=5). Major bleeding (adjusted
      hazard ratio, 1.53; 95% confidence interval, 1.20-1.96) and bleeding
      hospitalizations (adjusted hazard ratio, 1.52; 95% confidence interval, 1.17
      1.97) were significantly higher in those on OAC+ASA compared with those on OAC
      alone. Rates of ischemic events were low. CONCLUSIONS: Patients with AF receiving
      OAC are often treated with concomitant ASA, even when they do not have
      cardiovascular disease. Use of OAC+ASA was associated with significantly
      increased risk for bleeding, emphasizing the need to carefully determine if and
      when the benefits of concomitant ASA outweigh the risks in AF patients already on
      OAC. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE
      IDENTIFIER: NCT01165710.

PMID- 23861514
TI  - Radiotherapy of human sarcoma promotes an intratumoral immune effector signature.
AB  - PURPOSE: The tumor immune microenvironment plays a crucial role in the
      development and progression of cancer. Sarcomas are a group of heterogeneous soft
      tissue malignancies that are often treated with radiotherapy as a part of the
      treatment concept. There is increasing evidence that radiotherapy leads to
      alterations in the tumor microenvironment, particularly with respect to the
      immune infiltrate. This study has been carried out to develop a better
      understanding of such changes following radiotherapy. EXPERIMENTAL DESIGN: We
      retrospectively analyzed the expression of 35 immune response-related genes by
      quantitative reverse transcription PCR analysis and immunohistochemistry on
      paired formalin-fixed paraffin-embedded tumor samples from 38 sarcoma patients
      before and after radiotherapy. RESULTS: We observed that radiotherapy results in
      a significant upregulation of several immune effectors and cancer-testis antigens
      and a concomitant downregulation of immune suppressors, indicating that
      radiotherapy may support the immune defense in sarcomas. CONCLUSIONS: These novel
      findings may have implications for the design of therapeutic regimens which
      exploite the immune system in sarcoma patients by combining standard radiotherapy
      with immunotherapeutic strategies.

PMID- 23861515
TI  - Case report: Multimodality imaging of a cystic nephroma.
AB  - Cystic nephroma is a rare, benign, cystic neoplasm of the kidney. Its defining
      features include a discrete, complex cystic mass with multiple thin septations.
      Cystic nephroma often is confused with many different complex cystic masses of
      the kidney such as mixed epithelial stromal tumors, Wilms tumors, and cystic
      renal cell carcinoma. Patients typically do not present with symptoms, and it is
      often an incidental finding on imaging procedures for other diagnoses. Treatment
      for cystic nephroma can vary from frequent follow-up to nephrectomy or kidney
      sparing surgery. 

PMID- 23861516
TI  - Computed tomography x-ray tube life analysis: a multiyear study.
AB  - PURPOSE: To assess and compare actual computed tomography (CT) x-ray tube life
      with manufacturer warranty coverage limits because prolonging the tube life helps
      to lower operating costs. METHODS: Ten GE LightSpeed CT scanners with 40
      Performix Ultra tube changes and 3 GE VCT scanners with 10 Performix Pro tube
      changes were followed for 6 years. CT x-ray tube life measurements were performed
      by analyzing log files of the units after a tube change. RESULTS: The Ultra tubes
      warranty coverage limit is 70 kAs or 12 months, whichever comes first. For Pro
      tubes, it is 6000 examinations or 12 months, whichever comes first. Measurements
      for the Performix Ultra CT x-ray tubes showed a range of 7 to 48 months and 16.7
      to 239.9 kAs. Mean values for the Ultra CT x-ray tubes were 19.2 +/- 12.5 months
      and 81.0 +/- 45.4 kAs. Seven Ultra CT x-ray tubes did not meet the warranty
      coverage limits, with an average life of 8 months and 48.1 kAs. For the Pro CT x
      ray tubes, the measured logs indicated 22.4 +/- 9.6 months of CT x-ray tube life.
      All 10 Pro CT x-ray tubes exceeded company warranty coverage limits. DISCUSSION:
      Although Pro tubes lasted longer, they acquired fewer scans than did Ultra tubes.
      A similar result was shown for current output. CONCLUSION: Because the clinical
      demand for a CT scanner varies, it is difficult to determine the reason for the
      failed tubes. Mechanical, environmental, and usage factors can reduce the life
      expectancy of an x-ray tube.

PMID- 23861517
TI  - Mullerian duct anomalies and a case study of unicornuate uterus.
AB  - Early in pregnancy, the female embryo's reproductive system begins developing
      from the mullerian ducts. When development fails to progress normally, various
      anomalies of the uterus, vagina, and urinary system can result. In some cases,
      these anomalies cause infertility and other reproductive problems. This
      literature review discusses the 6 classes of mullerian duct anomalies, the
      complications associated with each, and the imaging examinations used to diagnose
      them and further evaluate uterine anatomy. In addition, a case study of a class
      II anomaly, known as unicornuate uterus, is presented. As reproductive medicine
      advances and more women seek diagnosis of and treatment for fertility problems,
      radiologic technologists need to be aware of duct anomalies and their appearance
      with various imaging modalities, including ultrasonography,
      hysterosalpingography, and magnetic resonance imaging. In addition, technologists
      must be sensitive to the emotional needs of patients with mullerian duct
      anomalies. 

PMID- 23861518
TI  - Alcoholic liver disease.
AB  - In the United States, approximately 100,000 deaths are attributed to alcohol
      abuse each year. In 2009, the World Health Organization listed alcohol use as one
      of the leading causes of the global burden of disease and injury. Alcoholic liver
      disease, a direct result of chronic alcohol abuse, insidiously destroys the
      normal functions of the liver. The end result of the disease, cirrhosis,
      culminates in a dysfunctional and diffusely scarred liver. This article discusses
      the clinical manifestations, imaging considerations, and treatment of alcoholic
      liver disease and cirrhosis. Normal liver function, liver hemodynamics, the
      disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

PMID- 23861519
TI  - Elbow disorders and injuries.
AB  - The elbow is a complex joint that supports forearm movement and consequently is
      at risk for various injuries and disorders. Elbow disorders can range from
      chronic to acute problems, many of which can be debilitating. This article
      explains the functional anatomy of the elbow joint and discusses the most common
      elbow disorders and injuries. It also presents the most common diagnostic imaging
      choices, along with typical acquisition methods. 

PMID- 23861520
TI  - Lateral positioning of the nasal bones using digital radiography.

PMID- 23861521
TI  - How do I get a case study published?

PMID- 23861522
TI  - Making assessment matter.

PMID- 23861523
TI  - VoiceThread: learning beyond the classroom walls.

PMID- 23861524
TI  - The mysterious island.

PMID- 23861525
TI  - Computed tomography of celiac disease.
AB  - Celiac disease is an autoimmune disorder that causes inflammation and destruction
      in the small intestine in response to the ingestion of gluten and related
      proteins. Although long considered a pediatric condition, it is now recognized as
      a condition that affects all ages, with significant complications if it goes
      untreated. Adults are most likely to present for imaging without a diagnosis for
      unspecified abdominal symptoms. Imaging the small intestine is complicated.
      Although the advent of multidetector computed tomography (CT) helps, the relative
      newness of its use, combined with the relative scarcity of imaging studies of
      celiac disease, make CT imaging of celiac disease a constantly evolving arena. 

PMID- 23861526
TI  - Quantum mottle and exposure indices.

PMID- 23861531
TI  - When should we do joint replacements? Early or late?

PMID- 23861532
TI  - Undifferentiated spondyloarthritis vs ankylosing spondylitis and psoriatic
      arthritis: a real-life prospective cohort study of clinical presentation and
      response to treatment.
AB  - OBJECTIVE: SpA is a phenotypically heterogeneous disease, with AS and PsA as its
      best studied subtypes. This study aimed to investigate whether, despite a
      different phenotypic presentation, patients with undifferentiated SpA (uSpA) have
      similar disease activity and response to treatment to those with AS and PsA.
      METHODS: 175 patients presenting at a dedicated SpA outpatient clinic were
      recruited in a real-life prospective cohort with follow-up every 3 months.
      Clinical characteristics, disease activity at presentation and response to
      treatment of uSpA were compared with AS and PsA. RESULTS: Twenty-three per cent
      (n = 40) of the patients were classified as uSpA. These patients were younger and
      tended to have a shorter disease duration than AS and PsA patients. uSpA patients
      exhibited a mixed axial (inflammatory back pain in 87.5%) and peripheral
      (peripheral arthritis in 62.5%) phenotype, with almost half of the patients
      having low-grade sacroiliitis on conventional X-ray. The overall disease activity
      in uSpA was similar to AS and higher than in PsA, also when analysing only anti
      TNF naive patients. Initiation of TNF blockade significantly decreased disease
      activity in uSpA, with a similar amplitude to that in AS and PsA. CONCLUSION:
      uSpA is a frequent, severe and anti-TNF-responsive phenotypic subtype of SpA. In
      agreement with the new ASAS classification criteria for axial and peripheral SpA
      and emerging data on TNF blockade in non-radiographic axial SpA and peripheral
      uSpA, these data emphasize the need for early diagnosis and optimal treatment of
      not only AS and PsA but also other SpA subforms.

PMID- 23861533
TI  - Functional disability in patients with rheumatoid arthritis admitted for
      multidisciplinary rehabilitation from 1992 to 2009.
AB  - OBJECTIVE: Advances in pharmacological care for RA have in general reduced
      functional disability. However, subgroups of patients may need treatment by a
      multidisciplinary team. This study aimed to describe the levels of functional
      ability and outcomes of patients with RA admitted for multidisciplinary
      rehabilitation in the past 20 years. METHODS: Data from three observational
      studies including four cohorts (1, 1992; 2a, 2001; 2b, 2003 and 3, 2008) on
      outcomes of multidisciplinary rehabilitation for RA patients conducted in one
      Dutch rheumatology clinic were used. Baseline and change scores of the HAQ were
      compared using a one-way analysis of variance with post hoc multiple comparisons
      (Bonferroni correction). RESULTS: The mean HAQ scores were 1.94 (s.d. 0.74) for
      cohort 1, 1.40 (0.74) and 1.39 (0.66) for cohorts 2a and 2b, respectively, and
      1.49 (0.59) for cohort 3, with the difference between cohort 1 on the one side
      and cohorts 2a/2b and 3 on the other side being statistically significant (P <
      0.01). The mean changes in HAQ score between admission and discharge were 0.24
      (s.d. 0.50) for cohort 1, 0.17 (0.49) for cohort 2a, 0.15 (0.37) for cohort 2b
      and 0.25 (0.46) for cohort 3. CONCLUSION: The level of functional disability of
      RA patients admitted for multidisciplinary rehabilitation decreased between 1992
      and 2001. The magnitude of improvement in functional ability during admission was
      in the same range in all three periods. These results suggest that in the era of
      MTX and biologics there are patients with RA who have considerable disability and
      benefit from multidisciplinary rehabilitation.

PMID- 23861534
TI  - Inhibition of spleen tyrosine kinase in the treatment of rheumatoid arthritis.
AB  - The pathogenesis of RA is a complex and ever-changing landscape but amid the
      chaos of the disease process we have found effective treatment regimes. However,
      our current therapeutics, although targeting various components of both the
      innate and adaptive immune response, do not result in disease remission. Protein
      kinase inhibitors are attractive targets due to their ability to influence
      downstream signalling and their oral bioavailability. Fostamatinib (R788)
      inhibits spleen tyrosine kinase (Syk) and has been in clinical trials involving
      both MTX inadequate responders (MTX-IRs) and biologic inadequate responders.
      Studies on the MTX-IR population revealed ACR20 responses of 67-72% at higher
      doses (150 mg bd and 100 mg bd), ACR50 responses of 43-57% and ACR70 responses of
      28-40%. The trial in the biologic non-responder population showed no efficacy,
      however, post hoc analyses of the data suggested that a further trial in this
      population is warranted. The most common adverse events included gastrointestinal
      effects, hypertension, neutropenia and transaminitis. Many adverse effects were
      dose responsive and hypertension was amenable to treatment. Upper respiratory
      tract infections were more likely at higher doses, but no serious infections with
      tuberculosis, fungi or opportunistic infections were reported. The oral
      availability of these agents makes them attractive treatment options for our
      patients, although the literature from the oncology field suggests that patients
      will only choose the oral route if efficacy is equivalent. Long-term follow-up
      studies are ongoing and will be critical for rare side effects. The role of these
      agents in our current arsenal is unclear and economic analyses are awaited. 

PMID- 23861537
TI  - Radiofrequency radiation leakage from microwave ovens.
AB  - This work presents data on the amount of radiation leakage from 117 microwave
      ovens in domestic and restaurant use in the West Bank, Palestine. The study of
      leakage is based on the measurements of radiation emissions from the oven in real
      life conditions by using a frequency selective field strength measuring system.
      The power density from individual ovens was measured at a distance of 1 m and at
      the height of centre of door screen. The tested ovens were of different types,
      models with operating powers between 1000 and 1600 W and ages ranging from 1
      month to >20 y, including 16 ovens with unknown ages. The amount of radiation
      leakage at a distance of 1 m was found to vary from 0.43 to 16.4 MUW cm(-2) with
      an average value equalling 3.64 MUW cm(-2). Leakages from all tested microwave
      ovens except for seven ovens (~6 % of the total) were below 10 MUW cm(-2). The
      highest radiation leakage from any tested oven was ~16.4 MUW cm(-2), and found in
      two cases only. In no case did the leakage exceed the limit of 1 mW cm(-2)
      recommended by the ICNIRP for 2.45-GHz radiofrequency. This study confirms a
      linear correlation between the amount of leakage and both oven age and operating
      power, with a stronger dependence of leakage on age.

PMID- 23861536
TI  - An innate twist between Crick's wobble and Watson-Crick base pairs.
AB  - Non-Watson-Crick pairs like the G.U wobble are frequent in RNA duplexes. Their
      geometric dissimilarity (nonisostericity) with the Watson-Crick base pairs and
      among themselves imparts structural variations decisive for biological functions.
      Through a novel circular representation of base pairs, a simple and general
      metric scheme for quantification of base-pair nonisostericity, in terms of
      residual twist and radial difference that can also envisage its mechanistic
      effect, is proposed. The scheme is exemplified by G.U and U.G wobble pairs, and
      their predicable local effects on helical twist angle are validated by MD
      simulations. New insights into a possible rationale for contextual occurrence of
      G.U and other non-WC pairs, as well as the influence of a G.U pair on other non
      Watson-Crick pair neighborhood and RNA-protein interactions are obtained from
      analysis of crystal structure data. A few instances of RNA-protein interactions
      along the major groove are documented in addition to the well-recognized
      interaction of the G.U pair along the minor groove. The nonisostericity-mediated
      influence of wobble pairs for facilitating helical packing through long-range
      interactions in ribosomal RNAs is also reviewed. 

PMID- 23861538
TI  - Intermittent drug techniques for schizophrenia.
AB  - Intermittent drug techniques refer to the "use of medication only during periods
      of incipient relapse or symptom exacerbation rather than continuously." The aim
      is to reduce the risk of adverse effects of antipsychotics by "reducing long-term
      medication exposure for patients who are receiving maintenance treatment while
      limiting risk of relapse," with a further goal of improving social functioning
      resulting from the reduction of antipsychotic-induced side effects. We reviewed
      the effects of different intermittent drug techniques compared with maintenance
      treatment in people with schizophrenia or related disorders. We searched The
      Cochrane Schizophrenia Group Trials Register (April 2012) and supplemented this
      by contacting relevant study authors and manually searching reference lists. All
      relevant randomized controlled trials (RCTs) were included.Of 241 records
      retrieved by the search, 17 trials were included. Homogenous data demonstrated
      that instances of relapse were significantly higher in people receiving any
      intermittent drug treatment in the long term (n=436, 7 RCTs, RR=2.46, 95% CI=1.70
      to 3.54). Intermittent treatment was shown to be more effective than placebo,
      however, and demonstrated that significantly less people receiving intermittent
      antipsychotics experienced full relapse by medium term (n=290, 2 RCTs, RR=0.37,
      95% CI=0.24-0.58). Intermittent antipsychotic treatment is not as effective as
      continuous, maintained antipsychotic therapy for preventing relapse in people
      with schizophrenia. It does seem, however, significantly better than no
      treatment. 

PMID- 23861535
TI  - Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal
      development, function, and dysfunction.
AB  - Precise control of messenger RNA (mRNA) processing and abundance are increasingly
      being recognized as critical for proper spatiotemporal gene expression,
      particularly in neurons. These regulatory events are governed by a large number
      of trans-acting factors found in neurons, most notably RNA-binding proteins
      (RBPs) and micro-RNAs (miRs), which bind to specific cis-acting elements or
      structures within mRNAs. Through this binding mechanism, trans-acting factors,
      particularly RBPs, control all aspects of mRNA metabolism, ranging from altering
      the transcription rate to mediating mRNA degradation. In this context the best
      characterized neuronal RBP, the Hu/ELAVl family member HuD, is emerging as a key
      component in multiple regulatory processes--including pre-mRNA processing, mRNA
      stability, and translation--governing the fate of a substantial amount of
      neuronal mRNAs. Through its ability to regulate mRNA metabolism of diverse groups
      of functionally similar genes, HuD plays important roles in neuronal development
      and function. Furthermore, compelling evidence indicates supplementary roles for
      HuD in neuronal plasticity, in particular, recovery from axonal injury, learning
      and memory, and multiple neurological diseases. The purpose of this review is to
      provide a detailed overview of the current knowledge surrounding the expression
      and roles of HuD in the nervous system. Additionally, we outline the present
      understanding of the molecular mechanisms presiding over the localization,
      abundance, and function of HuD in neurons.

PMID- 23861539
TI  - Altered striatal functional connectivity in subjects with an at-risk mental state
      for psychosis.
AB  - Recent functional imaging work in individuals experiencing an at-risk mental
      state (ARMS) for psychosis has implicated dorsal striatal abnormalities in the
      emergence of psychotic symptoms, contrasting with earlier findings implicating
      the ventral striatum. Our aims here were to characterize putative dorsal and
      ventral striatal circuit-level abnormalities in ARMS individuals using resting
      state functional magnetic resonance imaging (fMRI) and to investigate their
      relationship to positive psychotic symptoms. Resting-state fMRI was acquired in
      74 ARMS subjects and 35 matched healthy controls. An established method for
      mapping ventral and dorsal striatal functional connectivity was used to examine
      corticostriatal functional integrity. Positive psychotic symptoms were assessed
      using the Comprehensive Assessment of At-Risk Mental State and the Positive and
      Negative Syndrome Scale. Compared with healthy controls, ARMS subjects showed
      reductions in functional connectivity between the dorsal caudate and right
      dorsolateral prefrontal cortex, left rostral medial prefrontal cortex, and
      thalamus, and between the dorsal putamen and left thalamic and lenticular nuclei.
      ARMS subjects also showed increased functional connectivity between the ventral
      putamen and the insula, frontal operculum, and superior temporal gyrus
      bilaterally. No differences in ventral striatal (ie, nucleus accumbens)
      functional connectivity were found. Altered functional connectivity in
      corticostriatal circuits were significantly correlated with positive psychotic
      symptoms. Together, these results suggest that risk for psychosis is mediated by
      a complex interplay of alterations in both dorsal and ventral corticostriatal
      systems. 

PMID- 23861540
TI  - Receptor tyrosine kinases fall into distinct classes based on their inferred
      signaling networks.
AB  - Although many anticancer drugs that target receptor tyrosine kinases (RTKs)
      provide clinical benefit, their long-term use is limited by resistance that is
      often attributed to increased abundance or activation of another RTK that
      compensates for the inhibited receptor. To uncover common and unique features in
      the signaling networks of RTKs, we measured time-dependent signaling in six
      isogenic cell lines, each expressing a different RTK as downstream proteins were
      systematically perturbed by RNA interference. Network models inferred from the
      data revealed a conserved set of signaling pathways and RTK-specific features
      that grouped the RTKs into three distinct classes: (i) an EGFR/FGFR1/c-Met class
      constituting epidermal growth factor receptor, fibroblast growth factor receptor
      1, and the hepatocyte growth factor receptor c-Met; (ii) an IGF-1R/NTRK2 class
      constituting insulin-like growth factor 1 receptor and neurotrophic tyrosine
      receptor kinase 2; and (iii) a PDGFRbeta class constituting platelet-derived
      growth factor receptor beta. Analysis of cancer cell line data showed that many
      RTKs of the same class were coexpressed and that increased abundance of an RTK or
      its cognate ligand frequently correlated with resistance to a drug targeting
      another RTK of the same class. In contrast, abundance of an RTK or ligand of one
      class generally did not affect sensitivity to a drug targeting an RTK of a
      different class. Thus, classifying RTKs by their inferred networks and then
      therapeutically targeting multiple receptors within a class may delay or prevent
      the onset of resistance. 

PMID- 23861541
TI  - CCAAT/enhancer binding protein delta in macrophages contributes to
      immunosuppression and inhibits phagocytosis in nasopharyngeal carcinoma.
AB  - Although tumors tend to be associated with immune cells and inflammation, this
      immune response often fails to eliminate the cancer and instead promotes cancer
      progression. Tumor-associated macrophages (TAMs) fail to phagocytose tumor cells,
      and they also produce signals that suppress the adaptive immune response. We
      showed that immunosuppressive prostaglandin E2 (PGE2) led to the production and
      activity of the transcription factor CCAAT/enhancer binding protein delta
      (C/EBPdelta) by stimulating the nucleocytoplasmic shuttling of the RNA binding
      protein Hu antigen R (HuR), which bound to and stabilized CEBPD mRNA in
      macrophages. An increase in C/EBPdelta abundance in macrophages in response to
      PGE2 resulted in enhanced production of the immunosuppressive cytokine
      interleukin-10 (IL-10) and of pentraxin 3 (PTX3), which suppresses the ability of
      macrophages to phagocytose tumor cells. Furthermore, conditioned medium from
      C/EBPdelta-replete, but not C/EBPdelta-deficient, macrophages inhibited the
      phagocytosis of tumor cells by macrophages, suggesting an autocrine mode of
      regulation. Immunohistochemical analysis demonstrated that the amount of
      cytosolic HuR protein correlated with increased C/EBPdelta abundance in TAMs in
      malignant nasopharyngeal carcinoma. Together, these data suggest that the
      inflammatory PGE2-HuR-C/EBPdelta axis in macrophages promotes tumor progression
      by preventing the phagocytosis of tumor cells and inducing immunosuppressive
      cytokine production.

PMID- 23861544
TI  - Photo quiz: positive blood culture in a patient with sickle cell crisis. Answer:
      Klebsiella pneumoniae bacteremia showing filamentous forms and spheroplasts due
      to the presence of subinhibitory concentrations of beta-lactams.

PMID- 23861543
TI  - When and how should physicians determine the need for palliative and hospice care
      for patients with end-stage liver disease?: an experience in Taiwan.
AB  - We analyzed one case of end-stage liver disease and discussed whether the
      palliative care should be considered for this case. The medical record of a 56
      year-old woman with alcoholic liver cirrhosis admitted to our hospital due to
      hypovolemic shock and esophageal varices (EV) was reviewed. The EV with active
      bleeding were arrested by panendoscopic intervention. However, repeat surgery
      revealed transmural laceration over the cardia, and immediate surgery and
      splenectomy were needed. The patient died postoperatively in the surgical
      intensive care unit due to bleeding tendency and hypovolemic shock. We suggest
      that palliative care and/or hospice care should have been considered for this
      patient before the crisis developed and that physicians require education about
      timely palliative and hospice care for patients with end-stage nonmalignant
      disease. 

PMID- 23861547
TI  - Root hairs improve root penetration, root-soil contact, and phosphorus
      acquisition in soils of different strength.
AB  - Root hairs are a key trait for improving the acquisition of phosphorus (P) by
      plants. However, it is not known whether root hairs provide significant advantage
      for plant growth under combined soil stresses, particularly under conditions that
      are known to restrict root hair initiation or elongation (e.g. compacted or high
      strength soils). To investigate this, the root growth and P uptake of root hair
      genotypes of barley, Hordeum vulgare L. (i.e. genotypes with and without root
      hairs), were assessed under combinations of P deficiency and high soil strength.
      Genotypes with root hairs were found to have an advantage for root penetration
      into high-strength layers relative to root hairless genotypes. In P-deficient
      soils, despite a 20% reduction in root hair length under high-strength
      conditions, genotypes with root hairs were also found to have an advantage for P
      uptake. However, in fertilized soils, root hairs conferred an advantage for P
      uptake in low-strength soil but not in high-strength soil. Improved root-soil
      contact, coupled with an increased supply of P to the root, may decrease the
      value of root hairs for P acquisition in high-strength, high-P soils.
      Nevertheless, this work demonstrates that root hairs are a valuable trait for
      plant growth and nutrient acquisition under combined soil stresses. Selecting
      plants with superior root hair traits is important for improving P uptake
      efficiency and hence the sustainability of agricultural systems. 

PMID- 23861542
TI  - Release of nonmuscle myosin II from the cytosolic domain of tumor necrosis factor
      receptor 2 is required for target gene expression.
AB  - Tumor necrosis factor-alpha (TNF-alpha) elicits its biological activities through
      activation of TNF receptor 1 (TNFR1, also known as p55) and TNFR2 (also known as
      p75). The activities of both receptors are required for the TNF-alpha-induced
      proinflammatory response. The adaptor protein TNFR-associated factor 2 (TRAF2) is
      critical for either p55- or p75-mediated activation of nuclear factor kappaB (NF
      kappaB) and mitogen-activated protein kinase (MAPK) signaling, as well as for
      target gene expression. We identified nonmuscle myosin II (myosin) as a binding
      partner of p75. TNF-alpha-dependent signaling by p75 and induction of target gene
      expression persisted substantially longer in cells deficient in myosin regulatory
      light chain (MRLC; a component of myosin) than in cells replete in myosin. In
      resting endothelial cells, myosin was bound constitutively to the intracellular
      region of p75, a region that overlaps with the TRAF2-binding domain, and TNF
      alpha caused the rapid dissociation of myosin from p75. At early time points
      after exposure to TNF-alpha, p75 activated Rho-associated kinase 1 (ROCK1).
      Inhibition of ROCK1 activity blocked TNF-alpha-dependent phosphorylation of MRLC
      and the dissociation of myosin from p75. ROCK1-dependent release of myosin was
      necessary for the TNF-alpha-dependent recruitment of TRAF2 to p75 and for p75
      specific activation of NF-kappaB and MAPK signaling. Thus, our findings have
      revealed a previously uncharacterized, noncanonical regulatory function of myosin
      in cytokine signaling. 

PMID- 23861548
TI  - Colonization and persistence of urban ant populations as revealed by joint
      estimation of kinship and population genetic parameters.
AB  - The decrease in biodiversity due to increasing urbanization has been well
      documented, but the processes of colonization and maintenance of wildlife
      populations in urban areas remain poorly understood. We address this issue using
      462 individuals from 10 urban populations of the ant Formica japonica in Kobe
      City, Japan. We sampled workers regardless of colony identity, genotyped them
      using 6 microsatellite loci, and estimated allele frequencies and genotypes of
      reproductive individuals, together with other population genetic parameters, by
      estimating kinship structure using a likelihood method. Estimated genetic
      diversity and effective size of populations were not associated with
      environmental parameters, suggesting that populations are unaffected by
      urbanization. However, effective population sizes were small, and frequent
      population bottlenecks were detected. These results suggest that urban F.
      japonica populations are unstable, and the possibility of frequent extinctions
      and recolonizations in urban habitats. Populations were moderately differentiated
      without isolation by distance, suggesting a strong dispersal ability that enables
      colonization of urban habitats. Dispersal was male biased. Collectively, F.
      japonica was regarded as an urban adapter, which can colonize urban habitats by
      virtue of its preference for open ground and high dispersal ability but can
      persist in urban populations for only a short time, showing a tendency as a
      temporary urban inhabitant. 

PMID- 23861549
TI  - Biogeographic determinants of genetic diversification in the mouse opossum
      Gracilinanus agilis (Didelphimorphia: Didelphidae).
AB  - The genetic variation of Brazilian populations of the mouse opossum Gracilinanus
      agilis was analyzed on the basis of the mitochondrial Cytochrome b gene (mt-Cytb)
      and the exon 28 of the nuclear Von Willenbrand factor (e28-vWF). The radiation of
      Gracilinanus was dated at 4.80 Ma, with the appearance of G. agilis around 1.93
      Ma. Gracilinanus aceramarcae appeared as the first offshoot of the genus,
      followed by Gracilinanus emiliae and Gracilinanus microtarsus, which composed a
      sister clade of G. agilis. Phylogeographic analyses and genetic distance
      estimates indicate G. agilis as a single species, with haplotypes grouping in
      three well-supported clades, one from midwestern Brazil, a second one from
      northeastern Brazil, and a third one from eastern Brazil. Phylogeographic
      patterns in G. agilis were interpreted in search for congruence between genetic
      breaks and historic geomorphologic events documented for the region stretching
      northeastern to central-western of the Brazilian shield. The Rio Sao Francisco
      and the Serra Geral de Goias were found to represent relevant geographic barriers
      to gene flow for G. agilis populations as well as for populations of several
      other widespread taxa. 

PMID- 23861550
TI  - Plasmacytoid dendritic cells and CD8 T cells from pregnant women show altered
      phenotype and function following H1N1/09 infection.
AB  - BACKGROUND: Pregnant women are a high-risk group during influenza pandemics. In
      this study we determined whether plasmacytoid dendritic cells (pDCs) and CD8 T
      cells from pregnant women display altered activity following in vitro infection
      with 2009 pandemic swine influenza (H1N1/09). METHODS: Peripheral blood
      mononuclear cells (PBMCs) were isolated from pregnant (n = 26) and nonpregnant (n
      = 28) women. DC subtypes were enumerated from PBMCs. PBMCs were infected with
      H1N1/09 and CD86, human leukocyte antigen-DR (HLA-DR), and programmed death
      ligand 1/2 (PDL1/2) measured on pDCs. PD receptor 1 (PD1) was measured on CD8 T
      cells. Interferon-alpha (IFN-alpha), interleukin-2 (IL-2), tumor necrosis factor
      alpha (TNFalpha), and IFN-gamma were measured from culture supernatant. RESULTS:
      pDC (ie, CD303(+)/CD1c(-) PBMCs) percentages were lower in pregnant compared with
      nonpregnant women (P < .05). Following H1N1/09 infection, pDCs from pregnant
      women showed higher expression of CD86 (P < .01), HLA-DR (P < .001), and PDL1 (P
      < .001) compared with nonpregnant women. Expression of PD1 on CD8 T cells was
      higher during pregnancy (P < .05). Following H1N1/09 infection, PBMCs from
      pregnant women displayed reduced IFN-alpha (P < .01), IL-2 (P < .01), and IFN
      gamma (P < .01) compared with nonpregnant women. Blocking PDL1 during H1N1/09
      infection increased these cytokines during pregnancy (P < .05). CONCLUSION:
      Altered maternal cellular antiviral activity is implicated in the increased
      morbidity during pregnancy following influenza pandemics.

PMID- 23861551
TI  - Route of sexual exposure is independently associated with seropositivity to HPV
      16 and HPV-18 among clients of an STI clinic in the Netherlands.
AB  - We investigated the route of sexual exposure as a determinant for human
      papillomavirus (HPV)-16 and HPV-18 seropositivity. At the Amsterdam sexually
      transmitted infections clinic we recruited 4 risk groups: (1) men who have sex
      with women only (MSW; n = 751); (2) women who have sex with men (WSM; n = 749);
      (3) men who have sex with men (MSM) reporting insertive anal sex only (insMSM; n
      = 156); and (4) MSM reporting receptive anal sex (recMSM; n = 415). In
      multivariable analyses, HPV-16 seropositivity was significantly more common in
      WSM vs MSW, recMSM vs MSW, and recMSM vs insMSM. HPV-18 results were similar.
      Route of sexual exposure is independently associated with HPV seropositivity. 

PMID- 23861552
TI  - Kruppel-like factor 2 promotes liver steatosis through upregulation of CD36.
AB  - The Kruppel-like factor (KLF) family of transcription factors regulates diverse
      biological processes that include proliferation, differentiation, apoptosis,
      development, and responses to external stress. In the present study, we aim to
      investigate the roles of KLF2 in hepatic steatosis. Our results showed that mRNA
      and protein levels of KLF2 were significantly elevated in livers from obese mice.
      Adenoviruses-mediated overexpression of KLF2 induced accumulation of
      triglycerides in C57BL/6 mice, whereas KLF2 silencing ameliorates hepatosteatosis
      in ob/ob mice. At the molecular level, our data established CD36 as a novel
      transcriptional target of KLF2. KLF2 upregulated CD36 expression through a
      consensus binding site on its proximal promoter region. Additionally, the
      steatotic effect of KLF2 was dramatically inhibited in CD36-null mice. Therefore,
      our study reveals a novel link between KLF2-induced hepatic triglyceride
      accumulation and the expression of CD36. 

PMID- 23861553
TI  - Phenotypic and functional characteristic of a newly identified CD8+ Foxp3- CD103+
      regulatory T cells.
AB  - TGF-beta and Foxp3 expressions are crucial for the induction and functional
      activity of CD4(+)Foxp3(+) regulatory T (iTreg) cells. Here, we demonstrate that
      although TGF-beta-primed CD8(+) cells display much lower Foxp3 expression, their
      suppressive capacity is equivalent to that of CD4(+) iTreg cells, and both Foxp3(
      ) and Foxp3(+) CD8+ subsets have suppressive activities in vitro and in vivo.
      CD8(+)Foxp3(-) iTreg cells produce little IFN-gamma but almost no IL-2, and
      display a typical anergic phenotype. Among phenotypic markers expressed in
      CD8(+)Foxp3(-) cells, we identify CD103 expression particularly crucial for the
      generation and function of this subset. Moreover, IL-10 and TGF-beta signals
      rather than cytotoxicity mediate the suppressive effect of this novel Treg
      population. Therefore, TGF-beta can induce both CD8(+)Foxp3(-) and CD8(+)Foxp3(+)
      iTreg subsets, which may represent the unique immunoregulatory means to treat
      autoimmune and inflammatory diseases. 

PMID- 23861554
TI  - C60/N,N'-bis(1-naphthyl)-N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine:MoO3 as the
      interconnection layer for high efficient tandem blue fluorescent organic light
      emitting diodes.
AB  - The high efficient tandem blue fluorescent organic light emitting diodes (OLEDs)
      with the transparent interconnection layer (ICL) of fullerence (C60)/Molybdenum
      oxide (MoO3)-doped N,N'-bis(1-naphthyl)-N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine
      (NPB) were presented. A stack consisting of 0.5 nm of LiF and 1 nm of Ca, which
      is located from C60 to adjacent electron transporting layer is used as an
      electron injection layer. The experiment results indicate that the luminance of
      the tandem device is basically equal to that of the traditional single-unit
      device, but the current density of the tandem device is much less than that of
      the single-unit device under a same luminance. The current efficiency and the
      maximal power efficiency of tandem device with LiF/Ca/C60/NPB:MoO3/MoO3-based
      interconnection layer have been approximately enhanced by 250% and 126%,
      respectively. In addition, we also analyze that the mechanism of the efficiency
      enhancement is ascribed to the effective charge separation and transport of the
      ICL in tandem OLEDs.

PMID- 23861555
TI  - Spatiotemporal quantile regression for detecting distributional changes in
      environmental processes.
AB  - Climate change may lead to changes in several aspects of the distribution of
      climate variables, including changes in the mean, increased variability, and
      severity of extreme events. In this paper, we propose using spatiotemporal
      quantile regression as a flexible and interpretable method for simultaneously
      detecting changes in several features of the distribution of climate variables.
      The spatiotemporal quantile regression model assumes that each quantile level
      changes linearly in time, permitting straight-forward inference on the time trend
      for each quantile level. Unlike classical quantile regression which uses model
      free methods to analyze a single quantile or several quantiles separately, we
      take a model-based approach which jointly models all quantiles, and thus the
      entire response distribution. In the spatiotemporal quantile regression model,
      each spatial location has its own quantile function that evolves over time, and
      the quantile functions are smoothed spatially using Gaussian process priors. We
      propose a basis expansion for the quantile function that permits a closed-form
      for the likelihood, and allows for residual correlation modeling via a Gaussian
      spatial copula. We illustrate the methods using temperature data for the
      southeast US from the years 1931-2009. For these data, borrowing information
      across space identifies more significant time trends than classical non-spatial
      quantile regression. We find a decreasing time trend for much of the spatial
      domain for monthly mean and maximum temperatures. For the lower quantiles of
      monthly minimum temperature, we find a decrease in Georgia and Florida, and an
      increase in Virginia and the Carolinas.

PMID- 23861556
TI  - Prognostic impact of preoperative imaging parameters on resectability of hilar
      cholangiocarcinoma.
AB  - Objectives. To evaluate, in hilar cholangiocarcinoma (HCCA), the prognostic
      impact of specific preoperative radiologic parameters on resectability,
      metastases, and yield of laparoscopy, and to evaluate the currently used staging
      systems. Methods. Consecutive patients with HCCA presenting in our center from
      January 2003 through August 2010 were evaluated. Suspicion on lymph node
      metastasis, portal vein and hepatic artery involvement, lobar atrophy, and
      proximal extent of ductal invasion was scored. The prognostic value of these
      parameters for predicting resectability, yield of diagnostic laparoscopy,
      likelihood of metastatic disease, R0 resection, and survival was assessed. The
      Bismuth-Corlette classification and MSKCC staging system were evaluated. Results.
      Of all 289 evaluated patients, 158 patients (55%) had unresectable disease based
      on cross-sectional imaging studies or diagnostic laparoscopy; 131 patients (45%)
      underwent exploration. 83 patients (64%) underwent resection, of whom 67 (87%)
      had a radical (R0) resection. Suspicious lymph nodes and involvement of the
      hepatic artery were important prognostic factors for resectability. Predictive
      power of the evaluated staging systems was limited. Conclusions. Current staging
      systems predict resectability, but there is room for improvement. Hepatic artery
      involvement and nodal status might be important factors for prediction of
      resectability and should be considered in future staging systems. 

PMID- 23861557
TI  - Cone directionality from laser ray tracing in normal and LASIK patients.
AB  - Laser ray tracing, a technique originally developed to measure ocular aberrations
      from the deviations of the local ray aberrations as a function of entry pupil,
      was used to assess cone directionality in 29 normal eyes (seven of which
      underwent LASIK surgery) and seven eyes after LASIK corneal refractive surgery
      for myopia. The total intensity of the retinal aerial images was computed as a
      function of the entry location of the illuminated beam. The measured intensity
      distribution was fit to a two-dimensional Gaussian function plus a constant
      background. The maximum of the distribution represents the pupillary location
      toward which the cone photoreceptors are oriented (peak of the optical Stiles
      Crawford, SCE, function). We found the average SCE peak location was located 0.43
      +/- 0.96mm nasally and 0.60 +/- 0.87mm inferiorly to the center of the pupil. In
      general, there was not a relation between the pupillary area of best quality and
      SCE peak location, either pre-operatively or post-operatively. The cone
      directionality shape factor was also unchanged by surgery. However, in two eyes,
      pre- and post-operative SCE peak location changed significantly. LASIK refractive
      surgery decreased the MTF in all eyes, even when the actual SCE directionality of
      the subject is considered. In the two eyes that showed significantly different
      SCE peak location, the apodized post-operative MTF with the post-operative SCE
      peak exceeded the simulated post-operative MTF assuming no shift in the SCE peak.
      However, the statistical power of these two cases is low, and the general
      findings are consistent with the hypothesis that differences in optical quality
      are not a major driving mechanism for cone orientation.

PMID- 23861559
TI  - High sugar intake and development of skeletal muscle insulin resistance and
      inflammation in mice: a protective role for PPAR- delta agonism.
AB  - Peroxisome Proliferator Activated Receptor (PPAR)- delta agonists may serve for
      treating metabolic diseases. However, the effects of PPAR- delta agonism within
      the skeletal muscle, which plays a key role in whole-body glucose metabolism,
      remain unclear. This study aimed to investigate the signaling pathways activated
      in the gastrocnemius muscle by chronic administration of the selective PPAR-
      delta agonist, GW0742 (1 mg/kg/day for 16 weeks), in male C57Bl6/J mice treated
      for 30 weeks with high-fructose corn syrup (HFCS), the major sweetener in foods
      and soft-drinks (15% wt/vol in drinking water). Mice fed with the HFCS diet
      exhibited hyperlipidemia, hyperinsulinemia, hyperleptinemia, and
      hypoadiponectinemia. In the gastrocnemius muscle, HFCS impaired insulin and AMP
      activated protein kinase signaling pathways and reduced GLUT-4 and GLUT-5
      expression and membrane translocation. GW0742 administration induced PPAR- delta
      upregulation and improvement in glucose and lipid metabolism. Diet-induced
      activation of nuclear factor-kappaB and expression of inducible-nitric-oxide
      synthase and intercellular-adhesion-molecule-1 were attenuated by drug treatment.
      These effects were accompanied by reduction in the serum concentration of
      interleukin-6 and increase in muscular expression of fibroblast growth factor-21.
      Overall, here we show that PPAR- delta activation protects the skeletal muscle
      against the metabolic abnormalities caused by chronic HFCS exposure by affecting
      multiple levels of the insulin and inflammatory cascades.

PMID- 23861560
TI  - Low-density lipoproteins oxidation and endometriosis.
AB  - The etiopathogenesis of endometriosis still remains unknown. Recent data provide
      new valuable information concerning the role of oxidative stress in the
      pathophysiology of the disease. It has been proved that levels of different lipid
      peroxidation end products are increased in both peritoneal fluid (PF) and serum
      of endometriotic patients. We assessed the concentration of oxidized low-density
      lipoproteins (oxLDL) in PF of 110 women with different stages of endometriosis
      and 119 women with serous (n = 78) or dermoid (n = 41) ovarian cysts, as the
      reference groups. PF oxLDL levels were evaluated by ELISA. We found that
      concentrations of oxLDL in PF of endometriotic women were significantly higher
      compared to women with serous but not dermoid ovarian cysts. Interestingly, by
      analyzing concentrations of oxLDL in women with different stages of the disease,
      it was noted that they are significantly higher only in the subgroup of patients
      with stage IV endometriosis as compared to women with ovarian serous cysts. In
      case of minimal, mild, and moderate disease, PF oxLDL levels were similar to
      those noted in reference groups. Our results indicate that disrupted oxidative
      status in the peritoneal cavity of women with endometriosis may play a role in
      the pathogenesis of advanced stages of the disease. 

PMID- 23861558
TI  - Adipo-myokines: two sides of the same coin--mediators of inflammation and
      mediators of exercise.
AB  - This review summarizes the current literature regarding the most discussed
      contraction-regulated moykines like IL-6, IL-15, irisin, BDNF, ANGPTL4, FGF21,
      myonectin and MCP-1. It is suggested that the term myokine is restricted to
      proteins secreted from skeletal muscle cells, excluding proteins that are
      secreted by other cell types in skeletal muscle tissue and excluding proteins
      which are only described on the mRNA level. Interestingly, many of the
      contraction-regulated myokines described in the literature are additionally known
      to be secreted by adipocytes. We termed these proteins adipo-myokines. Within
      this review, we try to elaborate on the question why pro-inflammatory adipokines
      on the one hand are upregulated in the obese state, and have beneficial effects
      after exercise on the other hand. Both, adipokines and myokines do have autocrine
      effects within their corresponding tissues. In addition, they are involved in an
      endocrine crosstalk with other tissues. Depending on the extent and the kinetics
      of adipo-myokines in serum, these molecules seem to have a beneficial or an
      adverse effect on the target tissue. 

PMID- 23861561
TI  - Minimally modified LDL upregulates endothelin type A receptors in rat coronary
      arterial smooth muscle cells.
AB  - Minimally modified low-density lipoprotein (mmLDL) is a risk factor for
      cardiovascular disease. The present study investigated the effects of mmLDL on
      the expression of endothelin type A (ET(A)) receptors in coronary arteries. Rat
      coronary arteries were organ-cultured for 24 h. The contractile responses were
      recorded using a myographic system. ET(A) receptor mRNA and protein expressions
      were determined using real-time PCR and western blotting, respectively. The
      results showed that organ-culturing in the presence of mmLDL enhanced the
      arterial contractility mediated by the ET(A) receptor in a concentration
      dependent and time-dependent manner. Culturing with mmLDL (10  MU g/mL) for 24 h
      shifted the concentration-contractile curves toward the left significantly with
      increased E(max) of 228% +/- 20% from control of 100% +/- 10% and significantly
      increased ET(A) receptor mRNA and protein levels. Inhibition of the protein
      kinase C, extracellular signal-related kinases 1 and 2 (ERK1/2), or NF- kappa B
      activities significantly attenuated the effects of mmLDL. The c-Jun N-terminal
      kinase inhibitor or the p38 pathway inhibitor, however, had no such effects. The
      results indicate that mmLDL upregulates the ETA receptors in rat coronary
      arterial smooth muscle cells mainly via activating protein kinase C, ERK1/2, and
      the downstream transcriptional factor, NF- kappa B.

PMID- 23861562
TI  - Association of serum myeloid cells of soluble triggering receptor-1 level with
      myocardial dysfunction in patients with severe sepsis.
AB  - OBJECTIVE: To investigate the association of serum sTREM-1 with myocardial
      dysfunction in patients with severe sepsis. METHODS: A total of 85 patients with
      severe sepsis were divided into severe sepsis group (n = 40) and septic shock
      group (n = 45). Serum levels of sTREM-1, NT-proBNP, APACHE II score, SOFA score,
      cardiac index, cardiac function index, global ejection fraction, and left
      ventricular contractility index were measured on days 1, 3, and 7 after admission
      to ICU. RESULTS: Serum sTREM-1 levels of patients with septic shock were
      significantly higher than those with severe sepsis on days 1, 3, and 7. Serum
      sTREM-1 was positively correlated with APACHE II scores, SOFA scores, and NT
      proBNP. However, The sTREM-1 level was markedly negatively correlated with CI,
      CFI, GEF, and dP/dt max, respectively. Multiple logistic regression analysis
      showed that sTREM-1 was independent risk factor to NT-proBNP increasing. The
      optimal cut-off point of sTREM-1 for detecting patients with myocardial
      dysfunction was 468.05 ng/mL with sensitivity (80.6%) and specificity (75.7%).
      There is no difference in TREM-1-mRNA expression between the two groups.
      CONCLUSIONS: Serum sTREM-1 is significantly associated with myocardial
      dysfunction and may be a valuable tool for determining the presence of myocardial
      dysfunction in patients with severe sepsis.

PMID- 23861564
TI  - An alignment-free domain architecture similarity search (ADASS) algorithm for
      inferring homology between multi-domain proteins.
AB  - Annotations of the genes and their products are largely guided by inferring
      homology. Sequence similarity is the primary measure used for annotation purpose
      however, the domain content and order were given less importance albeit the fact
      that domain insertion, deletion, positional changes can bring in functional
      varieties. Of late, several methods developed quantify domain architecture
      similarity depending on alignments of their sequences and are focused on only
      homologous proteins. We present an alignment-free domain architecture-similarity
      search (ADASS) algorithm that identifies proteins that share very poor sequence
      similarity yet having similar domain architectures. We introduce a "singlet
      matching-triplet comparison" method in ADASS, wherein triplet of domains is
      compared with other triplets in a pair-wise comparison of two domain
      architectures. Different events in the triplet comparison are scored as per a
      scoring scheme and an average pairwise distance score (Domain Architecture
      Distance score - DAD Score) is calculated between protein domains architectures.
      We use domain architectures of a selected domain termed as centric domain and
      cluster them based on DAD score. The algorithm has high Positive Prediction Value
      (PPV) with respect to the clustering of the sequences of selected domain
      architectures. A comparison of domain architecture based dendrograms using ADASS
      method and an existing method revealed that ADASS can classify proteins depending
      on the extent of domain architecture level similarity. ADASS is more relevant in
      cases of proteins with tiny domains having little contribution to the overall
      sequence similarity but contributing significantly to the overall function. 

PMID- 23861563
TI  - Therapeutic effects of the superoxide dismutase mimetic compound MnIIMe2DO2A on
      experimental articular pain in rats.
AB  - Superoxide anion (O(2) (*-)) is overproduced in joint inflammation, rheumatoid
      arthritis, and osteoarthritis. Increased O(2) (*-) production leads to tissue
      damage, articular degeneration, and pain. In these conditions, the physiological
      defense against O(2) (*-), superoxide dismutases (SOD) are decreased. The Mn(II)
      complex MnL4 is a potent SOD mimetic, and in this study it was tested in
      inflammatory and osteoarticular rat pain models. In vivo protocols were approved
      by the animal Ethical Committee of the University of Florence. Pain was measured
      by paw pressure and hind limb weight bearing alterations tests. MnL4 (15 mg kg(
      1)) acutely administered, significantly reduced pain induced by carrageenan,
      complete Freund's adjuvant (CFA), and sodium monoiodoacetate (MIA). In CFA and
      MIA protocols, it ameliorated the alteration of postural equilibrium. When
      administered by osmotic pump in the MIA osteoarthritis, MnL4 reduced pain,
      articular derangement, plasma TNF alpha levels, and protein carbonylation. The
      scaffold ring was ineffective. MnL4 (10(-7) M) prevented the lipid peroxidation
      of isolated human chondrocytes when O(2) (*-) was produced by RAW 264.7. MnL4
      behaves as a potent pain reliever in acute inflammatory and chronic articular
      pain, being its efficacy related to antioxidant property. Therefore MnL4 appears
      as a novel protective compound potentially suitable for the treatment of joint
      diseases.

PMID- 23861565
TI  - SVM based model generation for binding site prediction on helix turn helix motif
      type of transcription factors in eukaryotes.
AB  - Support vector machine is a class of machine learning algorithms which uses a set
      of related supervised learning methods for classification and regression.
      Nowadays this method is vividly applied to many detection problems related with
      secondary structure, tumor cell and binding residue prediction. In this work,
      support vector machines (SVMs) have been trained on 90 sequences of transcription
      factors with HTH motif. Four sequence features were used as attribute for the
      prediction of interaction site in HTH motif. A web page was also developed so
      that user can easily enter the protein sequence and receive the output as
      interaction site predicted or not predicted. The generated model shows a very
      high amount of accuracy, sensitivity and specificity which proves to be a good
      model for the selected case. 

PMID- 23861566
TI  - In silico synteny based comparative genomics approach for identification and
      characterization of novel therapeutic targets in Chlamydophila pneumoniae.
AB  - Chlamydophila pneumoniae is one of the most important and well studied gram
      negative bacterial strain with respect to community acquired pneumonia and other
      respiratory diseases like Chronic obstructive pulmonary disease (COPD), Chronic
      asthma, Alzheimer's disease, Atherosclerosis and Multisclerosis which have a
      great potential to infect humans and many other mammals. According to WHO
      prediction, COPD is to become the third leading cause of death by 2030.
      Unfortunately, the molecular mechanisms leading to chronic infections are poorly
      understood and the difficulty in culturing C pneumoniae in experimental
      conditions and lack of entirely satisfactory serological methods for diagnosis is
      also a hurdle for drug discovery and development. We have performed an insilico
      synteny based comparative genomics analysis of C pneumoniae and other eight
      Chlamydial organisms to know the potential of C pneumoniae which cause COPD but
      other Chlamydial organisms lack in potential to cause COPD though some are
      involved in human pathogenesis. We have identified total 354 protein sequences as
      non-orthologous to other Chlamydial organisms, except hypothetical proteins 70
      were found functional out of which 60 are non homologous to Homo sapiens proteome
      and among them 18 protein sequences are found to be essential for survival of the
      C pneumoniae based on BLASTP search against DEG database of essential genes.
      CELLO analysis results showed that about 80% proteins are found to be
      cytoplasmic, Among which 5 were found as bacterial exotoxins and 2 as bacterial
      endotoxins, remaining 11 proteins were found to be involved in DNA binding, RNA
      binding, catalytic activity, ATP binding, oxidoreductase activity, hydrolase
      activity and proteolysis activity. It is expected that our data will facilitate
      selection of C pneumoniae proteins for successful entry into drug design
      pipelines. 

PMID- 23861567
TI  - Sequences encoding identical peptides for the analysis and manipulation of coding
      DNA.
AB  - The use of sequences encoding identical peptides (SEIP) for the in silico
      analysis of coding DNA from different species has not been reported; the study of
      such sequences could directly reveal properties of coding DNA that are
      independent of peptide sequences. For practical purposes SEIP might also be
      manipulated for e.g. heterologous protein expression. We extracted 1,551 SEIP
      from human and E. coli and 2,631 SEIP from human and D. melanogaster. We then
      analyzed codon usage and intercodon dinucleotide tendencies and found differences
      in both, with more conspicuous disparities between human and E. coli than between
      human and D. melanogaster. We also briefly manipulated SEIP to find out if they
      could be used to create new coding sequences. We hence attempted replacement of
      human by E. coli codons via dicodon exchange but found that full replacement was
      not possible, this indicated robust species-specific dicodon tendencies. To test
      another form of codon replacement we isolated SEIP from human and the jellyfish
      green fluorescent protein (GFP) and we then re-constructed the GFP coding DNA
      with human tetra-peptide-coding sequences. Results provide proof-of-principle
      that SEIP may be used to reveal differences in the properties of coding DNA and
      to reconstruct in pieces a protein coding DNA with sequences from a different
      organism, the latter might be exploited in heterologous protein expression. 

PMID- 23861568
TI  - in Silico analysis of Escherichia coli polyphosphate kinase (PPK) as a novel
      antimicrobial drug target and its high throughput virtual screening against
      PubChem library.
AB  - Multiple drug resistance (MDR) in bacteria is a global health challenge that
      needs urgent attention. The 2011 outbreak caused by Escherichia coli O104:H4 in
      Europe has exposed the inability of present antibiotic arsenal to tackle the
      problem of antimicrobial infections. It has further posed a tremendous burden on
      entire pharmaceutical industry to find novel drugs and/or drug targets.
      Polyphosphate kinase (PPK) in bacteria plays a crucial role in helping latter to
      adapt to stringent conditions of low nutritional availability thus making it a
      good target for antibacterials. In spite of this critical role, to best of our
      knowledge no in-silico work has been carried out to develop PPK as an antibiotic
      target. In the present study, virtual screening of PPK was carried out against
      all the 3D compounds with pharmacological action present in PubChem database. Our
      screening results were further refined by interaction maps to eliminate the false
      positive data respectively. From our results, compound number 5281927 (PubChem
      ID) has been found to have significant affinity towards affinity towards PPK
      active ATP-binding site indicating its therapeutic relevance. 

PMID- 23861569
TI  - Search for signatures in miRNAs associated with cancer.
AB  - Since the first discovery in the early 1990's, the predicted and validated
      population of microRNAs (miRNAs or miRs) has grown significantly. These small
      (~22 nucleotides long) regulators of gene expression have been implicated and
      associated with several genes in the cancer pathway as well. Globally, the
      identification and verification of microRNAs as biomarkers for cancer cell types
      has been the area of thrust for most miRNA biologists. However, there has been a
      noticeable vacuum when it comes to identifying a common signature or trademark
      that could be used to demarcate a miR to be associated with the development or
      suppression of cancer. To answer these queries, we report an in silico study
      involving the identification of global signatures in experimentally validated
      microRNAs which have been associated with cancer. This study has thrown light on
      the presence of significant common signatures, viz., - sequential and
      hybridization, which may distinguish a miR to be associated with cancer. Based on
      our analysis, we suggest the utility of such signatures in the design and
      development of algorithms for prediction of miRs involved in the cancer pathway. 

PMID- 23861570
TI  - Genome sequence and comparative analysis of Avibacterium paragallinarum.
AB  - BACKGROUND: Avibacterium paragallinarum, the causative agent of infectious
      coryza, is a highly contagious respiratory acute disease of poultry, which
      affects commercial chickens, laying hens and broilers worldwide. METHODOLOGY: In
      this study, we performed the whole genome sequencing, assembly and annotation of
      a Peruvian isolate of A. paragallinarum. Genome was sequenced in a 454 GS FLX
      Titanium system. De novo assembly was performed and annotation was completed with
      GS De Novo Assembler 2.6 using the H. influenzae str. F3031 gene model. Manual
      curation of the genome was performed with Artemis. Putative function of genes was
      predicted with Blast2GO. Virulence factors were identified by comparison with the
      Virulence Factor Database. RESULTS: The genome obtained has a length of 2.47 Mb
      with 40.66% of GC content. Seventy five large contigs (>500 nt) were obtained,
      which comprised 1,204 predicted genes. All the contigs are available in Genbank
      [GenBank: PRJNA64665]. A total of 103 virulence factors, reported in the
      Virulence Factor Database, were found in A. paragallinarum. Forty four of them
      are present in 7 species of Haemophilus, which are related with pathogenesis,
      virulence and host immune system evasion. A tetracycline-resistance associated
      transposon (Tn10), was found in A. paragallinarum, possibly acting as a defense
      mechanism. DISCUSSION AND CONCLUSION: The availability of A. paragallinarum
      genome represents an important source of information for the development of
      diagnostic tests, genotyping, and novel antigens for potential vaccines against
      infectious coryza. Identification of virulence factors contributes to better
      understanding the pathogenesis, and planning efforts for prevention and control
      of the disease.

PMID- 23861571
TI  - Development of web based database on biochemical characteristics of rapeseed
      mustard.
AB  - Rapeseed-mustard oil is an essential dietary component, in India. The
      modification of rapeseed- mustard for fatty acid composition of seed oil to
      develop new genotypes having alternative oil and meal characteristics has been an
      important objective in quality breeding. Moreover, Breeding efforts in India are
      in progress to develop double low varieties to meet the internationally
      acceptable standards of oil and seed meal. So, information on the nutritional and
      anti-nutritional make-up of rapeseed-mustard oil and seed meal of the existing
      germplasm would be quite useful for the researchers especially breeders involved
      in the quality improvement programmes. In the present study database on
      biochemical characteristics of rapeseed-mustard has been developed using open
      source technology LAMP. The database provides the information on 14 important
      biochemical characters such as oil, saturated fatty acids, oleic, linoleic,
      linolenic, eicosenoic, erucic acid, monounsaturated fatty acids (MUFA),
      polyunsaturated fatty acids (PUFA), omega6/omega3 ratio, protein, glucosinolate,
      phenol, and fiber content. It offers web interface to submit and search data in
      the database. The database presently comprises biochemical characteristics of
      germplasm accessions, advance breeding lines and notified varieties of rapeseed
      mustard. The database developed will be useful to the breeders in the selection
      of desired genotype with specific traits. 

PMID- 23861572
TI  - GMATo: A novel tool for the identification and analysis of microsatellites in
      large genomes.
AB  - Simple Sequence Repeats (SSR), also called microsatellite, is very useful for
      genetic marker development and genome application. The increasing whole sequences
      of more and more large genomes provide sources for SSR mining in silico. However
      currently existing SSR mining tools can't process large genomes efficiently and
      generate no or poor statistics. Genome-wide Microsatellite Analyzing Tool (GMATo)
      is a novel tool for SSR mining and statistics at genome aspects. It is faster and
      more accurate than existed tools SSR Locator and MISA. If a DNA sequence was too
      long, it was chunked to short segments at several Mb followed by motifs
      generation and searching using Perl powerful pattern match function. Matched loci
      data from each chunk were then merged to produce final SSR loci information. Only
      one input file is required which contains raw fasta DNA sequences and output
      files in tabular format list all SSR loci information and statistical
      distribution at four classifications. GMATo was programmed in Java and Perl with
      both graphic and command line interface, either executable alone in platform
      independent manner with full parameters control. Software GMATo is a powerful
      tool for complete SSR characterization in genomes at any size. AVAILABILITY: The
      soft GMATo is freely available at
      http://sourceforge.net/projects/gmato/files/?source=navbar or on contact.

PMID- 23861573
TI  - SpecP: A tool for spectral partitioning of protein contact graph.
AB  - SpecP is an open-source Python module that performs Spectral Partitioning on
      Protein Contact Graphs. Protein Contact Graphs are graph theory based
      representation of the protein structure, where each amino acid forms a 'vertex'
      and spatial contact of any two amino acids is an 'edge' between them. Spectral
      partitioning is carried out in SpecP based on the second smallest spectral value
      (eigen value) of the Protein Contact Graph. The eigen vector corresponding to the
      second smallest spectral value are partitioned into two clusters based on the
      sign of the corresponding vector entry. Spectral Partitioning algorithm is
      repeatedly carried out until the desired numbers of partitions are obtained.
      SpecP visualizes the spectrally partitioned clusters of protein structure along
      with the Protein Contact Map and Protein Contact Graph which can be saved for
      later use. It also possesses an interactive mode whereby the user has the ability
      to zoom, pan, resize and save these raster images in various image formats (.eps,
      .jpg, .png) manually. SpecP is a stand-alone extensible tool useful for
      structural analysis of proteins. 

PMID- 23861574
TI  - Vaginal colonization by papG allele II+ Escherichia coli isolates from pregnant
      and nonpregnant women as predisposing factor to pyelonephritis.
AB  - Vaginal (61) and fecal (61) Escherichia coli isolates from pregnant and
      nonpregnant women (18-45 years old) were surveyed for papG alleles by PCR
      technique. papG allele II was the most prevalent among both vaginal (32.7%) and
      fecal (3.2%) isolates, whereas other alleles were found only among vaginal
      isolates (1.6% for alleles I and III and 3.2% for alleles II + III). papG(+)
      pregnant women's isolates did not differ significantly from those of nonpregnant
      in possession of papG allele II (90% versus 73.3%), whereas both (32.7%) differed
      significantly (P <= 0.05) in comparison with fecal isolates (3.2%). The vast
      majority of papG allele II(+) vaginal isolates were clustered in group B2 (81.8%)
      and much less in group D (18.1%). Also, most of them were positive for fimH
      (100%), papC (100%), iucC (90.9%), and hly (72.7%), and about half of them were
      positive for sfa/foc (45.4%). In addition, the mean of VFs' gene possession was
      3.5 (range from 2 to 5). It can be concluded that vaginal colonization by papG
      allele II(+) E. coli is possibly one of the predisposing factors of both pregnant
      and nonpregnant women to pyelonephritis, but its potential may be modified by
      other factors especially host factors.

PMID- 23861575
TI  - Non-arteritic anterior ischemic optic neuropathy secondary to acute primary-angle
      closure.
AB  - PURPOSE: To describe a case of non-arteritic ischemic optic neuropathy (NAION)
      secondary to acute primary-angle closure (APAC). METHODS: Case report. RESULTS: A
      50-year-old woman with painful visual loss in the right eye was found to be in
      APAC with a right afferent pupillary defect. Laser peripheral iridotomy relieved
      pain but did not improve vision. Diffuse optic disc edema in the right eye and a
      small cup-to-disc ratio in the left eye were evident. Magnetic resonance imaging
      was normal. The patient was diagnosed with non-arteritic ischemic optic
      neuropathy (NAION) secondary to APAC, a rare clinical entity which can result in
      markedly decreased visual acuity. CONCLUSION: NAION secondary to APAC is a rare
      clinical entity that can result in severe vision loss.

PMID- 23861576
TI  - Lymphocyte infiltration in CAPN5 autosomal dominant neovascular inflammatory
      vitreoretinopathy.
AB  - PURPOSE: To describe immunohistopathological findings in autosomal dominant
      neovascular inflammatory vitreoretinopathy (ADNIV). METHODS: An enucleated eye
      specimen from a patient with Stage V ADNIV was examined using standard
      histopathological methods and lymphocyte markers. RESULTS: A c.731T>C CAPN5
      mutation resulted in a p.Leu244Pro substitution in calpain-5. The eye showed
      exudative retinal detachment and neovascularization, intraocular fibrosis, and
      features of phthisis bulbi. Chronic inflammatory CD3-positive cell infiltrates
      were identified throughout the uvea, vitreous and retina, consistent with chronic
      uveitis. CONCLUSION: Mutations in CAPN5 trigger autoimmune uveitis characterized
      by inflammatory T-cells and severe neovascularization.

PMID- 23861577
TI  - Choroidal neovascularization after blunt ocular trauma in angioid streaks.
AB  - BACKGROUND: Patients with angioid streaks are prone to develop a subretinal
      hemorrhage after ocular injury, due to fragility of Bruch's membrane. OBJECTIVE:
      The purpose of this study was to report a patient with angioid streaks in whom
      subfoveal choroidal neovascularization (CNV) developed after blunt ocular trauma.
      CASE REPORT: A 60-year-old man was accidentally struck in the left eye with a
      crowbar handle while engaged in the demolition of wooden building materials in
      May 2011 and was initially evaluated at our hospital. Corrected visual acuity was
      0.3 in the right and 1.2 in the left eye, and relative afferent pupillary defect
      was negative. Funduscopy revealed choroidal atrophy around the optic papillae and
      angioid streaks radiating from around the optic discs in both eyes. In the right
      eye, there was macular atrophy. In the left eye, there was a subretinal
      hemorrhage around the macular region. Fluorescein angiography of the left eye
      showed a blockage due to subretinal hemorrhage and increasing hyperfluorescent
      spots superior to the fovea, suggestive of extrafoveal CNV. Spectral-domain
      optical coherence tomography showed macular thinning in the right eye and no
      obvious abnormalities near the subfoveal region in the left eye. Two months
      later, the patient noticed decreased visual acuity in the left eye and was
      reevaluated. Visual acuity had decreased to 0.7, and well-defined CNV, one disc
      diameter in size, was presenting slightly superior to the macula, including the
      subfoveal region. Two weeks later, anti-vascular endothelial growth factor (anti
      VEGF) antibody (bevacizumab) was injected intravitreally; the CNV then regressed,
      and visual acuity improved to 1.2. CONCLUSION: Marked improvement in visual
      acuity with early treatment has not been reported in angioid streaks with
      subfoveal CNV after ocular injury. Intravitreal injection of an anti-VEGF
      antibody should be considered early after the diagnosis of CNV.

PMID- 23861578
TI  - Non-Descemet's stripping automated endothelial keratoplasty for bullous
      keratopathy secondary to iridoschisis.
AB  - PURPOSE: To report a case of bullous keratopathy secondary to iridoschisis
      treated by non-Descemet's stripping automated endothelial keratoplasty (nDSAEK).
      CASE REPORT: A 79-year-old woman was referred to our hospital with loss of vision
      in the left eye. Slit lamp examination of her left eye showed a shallow anterior
      chamber with cataract and schisis in the inferior quadrant of iris stroma.
      Bullous keratopathy secondary to iridoschisis was diagnosed. Cataract surgery
      with iridectomy succeeded to deepen the anterior chamber and remove the floating
      iris leaf, although corneal edema remained. Four days later, nDSAEK was
      performed, which resolved corneal edema and restored visual acuity. CONCLUSION:
      The two-step surgery of cataract surgery plus iridectomy followed by nDSAEK may
      be an effective strategy for treating bullous keratopathy secondary to
      iridoschisis.

PMID- 23861579
TI  - Twelve months of follow-up after intravitreal injection of ranibizumab for the
      treatment of idiopathic parafoveal telangiectasia.
AB  - AIMS: To report the anatomic and functional outcomes of intravitreal ranibizumab
      in idiopathic parafoveal telangiectasia (IPT). MATERIAL AND METHODS: Four eyes of
      three patients were included in this interventional case series. One patient (two
      eyes) had bilateral IPT (type 2) and two patients (two eyes) had unilateral (type
      1) IPT. Retreatment was scheduled in case of leakage persistence in combination
      with visual acuity (VA) deterioration. Fluorescein angiography and optical
      coherence tomography were performed together with a full ophthalmic examination
      at baseline, 1, 3, 6, 9, and 12 months after injection. RESULTS: One intravitreal
      injection of ranibizumab was performed in all four eyes. Complete cessation of
      leakage was documented postintervention in three eyes and partial cessation in
      one eye, followed by improvement of best corrected VA in one of them. In all
      eyes, structural changes of the photoreceptor layer were detected in tomography
      and were responsible for visual loss, which was in most cases, refractory to the
      applied therapy. CONCLUSION: Use of ranibizumab might be efficient in eliminating
      leakage activity in the macular region in patients with IPT. Nevertheless,
      improvement in VA was infrequent. Preexisting early photoreceptor alteration in
      IPT might render such patients unable to improve VA.

PMID- 23861580
TI  - Complex sleep apnea syndrome.
AB  - Complex sleep apnea syndrome (CompSAS) is a distinct form of sleep-disordered
      breathing characterized as central sleep apnea (CSA), and presents in obstructive
      sleep apnea (OSA) patients during initial treatment with a continuous positive
      airway pressure (CPAP) device. The mechanisms of why CompSAS occurs are not well
      understood, though we have a high loop gain theory that may help to explain it.
      It is still controversial regarding the prevalence and the clinical significance
      of CompSAS. Patients with CompSAS have clinical features similar to OSA, but they
      do exhibit breathing patterns like CSA. In most CompSAS cases, CSA events during
      initial CPAP titration are transient and they may disappear after continued CPAP
      use for 4~8 weeks or even longer. However, the poor initial experience of CompSAS
      patients with CPAP may not be avoided, and nonadherence with continued therapy
      may often result. Treatment options like adaptive servo-ventilation are available
      now that may rapidly resolve the disorder and relieve the symptoms of this
      disease with the potential of increasing early adherence to therapy. But these
      approaches are associated with more expensive and complicated devices. In this
      review, the definition, potential plausible mechanisms, clinical characteristics,
      and treatment approaches of CompSAS will be summarized. 

PMID- 23861581
TI  - Short- and long-term mortality in males and females with fragility hip fracture
      in Norway. A population-based study.
AB  - BACKGROUND: Hip fracture patients have, in several studies, been shown to have
      excessive mortality. There is, however, a lack of mortality data, in comparison
      to incidence data, from the last decade in particular. OBJECTIVE: To study short-
      and long-term mortality in a population-based cohort of hip fracture patients
      over the last decade and compare it to the background population. PATIENTS AND
      METHODS: Fragility hip fracture patients in the two most southern counties in
      Norway who experienced fractures in 2004 and 2005 were studied. For each patient,
      three controls were randomly recruited from the background population matched for
      age, sex, and residency. Overall, age-, gender-, and group-specific mortality
      rates were calculated. RESULTS: A total of 942 (267 male and 675 female) patients
      with a fragility hip fracture were identified. In the hip fracture patients,
      overall mortality rate after 1 year was 21.3% (males 30.7% and females 19.1%, P <
      0.005) and, after 5 years, 59.0% (males 70.0% and females 54.6%, P < 0.005). The
      corresponding figures for matched controls were 5.6% (males 5.9%, females 5.4%, P
      = 0.6) and 24.9% (males 25.9%, females 24.5%, P = 0.4), respectively. A
      statistically significant difference was seen in the log-rank statistical
      analysis between hip fracture patients and controls, both in males (P < 0.0005)
      and females (P < 0.0005), and for age groups 50-80 years (P < 0.0005) and 80
      years and older (P < 0.0005). CONCLUSION: Mortality in males and females with hip
      fractures is high not only in the first year after fracture, but remains higher
      than in the background population during 5 years of follow-up. The high mortality
      in hip fracture patients remains a challenge both in middle-aged and elderly
      individuals. Optimization of post-fracture treatment and care could reduce
      mortality of hip fracture in middle-aged and elderly individuals.

PMID- 23861582
TI  - Response to vitamin D and depression in geriatric primary care patients.

PMID- 23861583
TI  - Chrysopogon zizanioides aqueous extract mediated synthesis, characterization of
      crystalline silver and gold nanoparticles for biomedical applications.
AB  - The exploitation of various plant materials for the biosynthesis of nanoparticles
      is considered a green technology as it does not involve any harmful chemicals.
      The aim of this study was to develop a simple biological method for the synthesis
      of silver and gold nanoparticles using Chrysopogon zizanioides. To exploit
      various plant materials for the biosynthesis of nanoparticles was considered a
      green technology. An aqueous leaf extract of C. zizanioides was used to
      synthesize silver and gold nanoparticles by the bioreduction of silver nitrate
      (AgNO3) and chloroauric acid (HAuCl4) respectively. Water-soluble organics
      present in the plant materials were mainly responsible for reducing silver or
      gold ions to nanosized Ag or Au particles. The synthesized silver and gold
      nanoparticles were characterized by ultraviolet (UV)-visible spectroscopy,
      scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX),
      Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD)
      analysis. The kinetics decline reactions of aqueous silver/gold ion with the C.
      zizanioides crude extract were determined by UV-visible spectroscopy. SEM
      analysis showed that aqueous gold ions, when exposed to the extract were reduced
      and resulted in the biosynthesis of gold nanoparticles in the size range 20-50
      nm. This eco-friendly approach for the synthesis of nanoparticles is simple, can
      be scaled up for large-scale production with powerful bioactivity as demonstrated
      by the synthesized silver nanoparticles. The synthesized nanoparticles can have
      clinical use as antibacterial, antioxidant, as well as cytotoxic agents and can
      be used for biomedical applications. 

PMID- 23861584
TI  - Lyophilized phytosomal nanocarriers as platforms for enhanced diosmin delivery:
      optimization and ex vivo permeation.
AB  - Diosmin (DSN) is an outstanding phlebotonic flavonoid with a tolerable potential
      for the treatment of colon and hepatocellular carcinoma. Being highly insoluble,
      DSN bioavailability suffers from high inter-subject variation due to variable
      degrees of permeation. This work endeavored to develop novel DSN loaded
      phytosomes in order to improve drug dissolution and intestinal permeability.
      Three preparation methods (solvent evaporation, salting out, and lyophilization)
      were compared. Nanocarrier optimization encompassed different soybean
      phospholipid (SPC) types, different solvents, and different DSN:SPC molar ratios
      (1:1, 1:2, and 1:4). In vitro appraisal encompassed differential scanning
      calorimetry, infrared spectroscopy, particle size, zeta potential, polydispersity
      index, transmission electron microscopy, drug content, and in vitro stability.
      Comparative dissolution studies were performed under sink versus non-sink
      conditions. Ex vivo intestinal permeation studies were performed on rats
      utilizing noneverted sac technique and high-performance liquid chromatography
      analysis. The results revealed lyophilization as the optimum preparation
      technique using SPC and solvent mixture (Dimethyl sulphoxide:t-butylalchol) in a
      1:2 ratio. Complex formation was contended by differential scanning calorimetry
      and infrared data. Optimal lyophilized phytosomal nanocarriers (LPNs) exhibited
      the lowest particle size (316 nm), adequate zeta-potential (-27 mV), and good in
      vitro stability. Well formed, discrete vesicles were revealed by transmission
      electron microscopy, drug content, and in vitro stability. Comparative
      dissolution studies were performed. LPNs demonstrated significant enhancement in
      DSN dissolution compared to crude drug, physical mixture, and generic and brand
      DSN products. Permeation studies revealed 80% DSN permeated from LPNs via
      oxygenated rat intestine compared to non-detectable amounts from suspension. In
      this study, LPNs (99% drug loading) could be successfully tailored for DSN with
      improved dissolution and permeation characteristics, which is promising for
      lowering the influence of exogenous factors and increasing drug delivery. 

PMID- 23861585
TI  - Hyaluronan-cisplatin conjugate nanoparticles embedded in Eudragit S100-coated
      pectin/alginate microbeads for colon drug delivery.
AB  - Hyaluronan-cisplatin conjugate nanoparticles (HCNPs) were chosen as colon
      targeting drug-delivery carriers due to the observation that a variety of
      malignant tumors overexpress hyaluronan receptors. HCNPs were prepared by mixing
      cisplatin with a hyaluronan solution, followed by dialysis to remove trace
      elements. The cells treated with HCNPs showed significantly lower viability than
      those treated with cisplatin alone. HCNPs were entrapped in Eudragit S100-coated
      pectinate/alginate microbeads (PAMs) by using an electrospray method and a
      polyelectrolyte multilayer-coating technique in aqueous solution. The release
      profile of HCNPs from Eudragit S100-coated HCNP-PAMs was pH-dependent. The
      percentage of 24-hour drug release was approximately 25.1% and 39.7% in pH 1.2
      and pH 4.5 media, respectively. However, the percentage of drug released quickly
      rose to 75.6% at pH 7.4. Moreover, the result of an in vivo nephrotoxicity study
      demonstrated that Eudragit S100-coated HCNP-PAMs treatment could mitigate the
      nephrotoxicity that resulted from cisplatin. From these results, it can be
      concluded that Eudragit S100-coated HCNP-PAMs are promising carriers for colon
      specific drug delivery.

PMID- 23861587
TI  - Nigerian medical students' opinions about individuals who use and abuse
      psychoactive substances.
AB  - Substance use disorders are prevalent in Nigeria. The number of available
      specialist health providers is inadequate to fill the treatment gap.
      Interventions can be provided by nonspecialist health providers and have been
      found to be beneficial. However, attitudes toward substance misuse and misusers
      can impede the provision of this service. We aimed to determine attitudes of
      medical trainees toward substance use by utilizing a modified form of the
      Substance Abuse Attitude Scale (SAAS). Medical students (n = 200) had positive
      attitudes toward individuals who misuse psychoactive substances. The medial
      students, however, preferred treatment to be offered by trained specialists and
      held restrictive views regarding cannabis and alcohol use. More positive
      attitudes were expressed by participants who were male or had a lifetime history
      of psychoactive substance use. The role of personal and family-related
      psychoactive substance use factors are probably associated with attitudinal
      responses and would require further exploration. 

PMID- 23861586
TI  - Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles
      in mice.
AB  - Gold nanoparticles have received wide interest in disease diagnosis and therapy,
      but one of the important issues is their toxicological effects in vivo. Sex
      differences in the toxicity of gold nanoparticles are not clear. In this work,
      body weight, organ weight, hematology, and biochemistry were used to evaluate sex
      differences in immune response and liver and kidney damage. Pathology was used to
      observe the general toxicity of reproductive organs. The immune response was
      influenced significantly in female mice, with obvious changes in spleen and
      thymus index. Hematology results showed that male mice treated with 22.5 nm gold
      nanoparticles received more significant infection and inflammation than female
      mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold
      nanoparticles caused more significant liver damage in male mice than female mice,
      while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney
      damage in female mice than male mice. No significant toxicological response was
      found in the reproductive system for female or male mice. It was found that gold
      nanoparticles caused more serious liver toxicity and infection in male mice than
      female mice. These findings indicated that sex differences may be one of the
      important elements for in vivo toxicity of gold nanoparticles. 

PMID- 23861588
TI  - Trace amine associated receptor 1 modulates behavioral effects of ethanol.
AB  - BACKGROUND: Few treatment options for alcohol use disorders (AUDs) exist and more
      are critically needed. Here, we assessed whether trace amine associated receptor
      1 (TAAR1), a modulator of brain monoamine systems, is involved in the behavioral
      and reinforcement-related effects of ethanol and whether it could potentially
      serve as a therapeutic target. METHODS: Wild-type (WT) and TAAR1 knockout (KO)
      mice (75% C57J/BL6 and 25% 129S1/Sv background) were compared in tests of ethanol
      consumption (two-bottle choice [TBC]), motor impairment (loss of righting reflex,
      [LORR], locomotor activity) and ethanol clearance (blood ethanol level [BEL]).
      RESULTS: As compared with WT mice, KO mice displayed (1) significantly greater
      preference for and consumption of ethanol in a TBC paradigm (3%-11% vol/vol
      escalating over 10 weeks), with no significant difference observed in TBC with
      sucrose (1%-3%); (2) significantly greater sedative-like effects of acute ethanol
      (2.0 or 2.5 g/kg, intraperitoneal [i.p.]) manifested as LORR observed at a lower
      dose and for longer time, with similar BELs and rates of ethanol clearance; and
      (3) lower cumulative locomotor activity over 60 minutes in response to an acute
      ethanol challenge (1.0-2.5 g/kg, i.p.). CONCLUSIONS: The present findings are the
      first to implicate TAAR1 in the behavioral and reinforcement-related effects of
      ethanol and raise the question of whether specific drugs that target TAAR1 could
      potentially reduce alcohol consumption in humans with AUDs.

PMID- 23861589
TI  - Clinical significance of the thymidylate synthase, dihydropyrimidine
      dehydrogenase, and thymidine phosphorylase mRNA expressions in hepatocellular
      carcinoma patients receiving 5-fluorouracil-based transarterial chemoembolization
      treatment.
AB  - PURPOSE: To determine whether 5-fluorouracil (5-FU) sensitivity is associated
      with the mRNA expressions of thymidylate synthase (TS), dihydropyrimidine
      dehydrogenase (DPD), and thymidine phosphorylase (TP) in patients with
      hepatocellular carcinoma (HCC) treated with 5-FU-based transarterial
      chemoembolization (TACE). METHODS: Formalin-fixed, paraffin-embedded tumor
      specimens from 40 patients treated with 5-FU-based TACE were selected for the
      examination of TS, DPD, and TP expression level by a quantitative real-time
      reverse transcription- polymerase chain reaction (PCR) technique. Patients were
      categorized into high and low expression groups according to the median
      expression level of each enzyme. Associations between the mRNA expression levels
      of TS, DPD, and TP and clinical parameters including treatment efficacies,
      clinicopathological factors, and prognosis were assessed. RESULTS: High DPD
      expression was associated with worse treatment outcome, including intrahepatic
      disease progression rate (hazard ratio [HR] for high DPD versus low DPD, 2.212;
      95% confidence interval [CI], 1.030-4.753; P = 0.042), extrahepatic disease
      progression rate (HR for high versus low DPD, 3.171; 95% CI, 1.003-10.023; P =
      0.049), and progression-free survival (HR for high versus low DPD, 2.308; 95% CI,
      1.102-4.836; P = 0.027). No correlation was found between the mRNA expression of
      TS/TP and treatment outcome. CONCLUSION: DPD mRNA expression level was negatively
      correlated with the clinical outcomes of HCC patients treated with 5-FU-based
      TACE. These results provide indirect evidence that high DPD mRNA expression is a
      predictive marker of treatment resistance for 5-FU.

PMID- 23861590
TI  - A cost-of-illness study of spina bifida in Italy.
AB  - INTRODUCTION: Spina bifida (SB) is a congenital malformation of the spinal cord,
      nerves, and adjacent covering structures, with different levels of severity and
      functional disability. The economic cost of spina bifida and its prevention using
      folic acid have never been estimated in Italy. This study was conducted to define
      the cost of illness of SB in Italy. METHODS: A retrospective multicenter
      observational study on the social cost of patients with SB was carried out in
      three SB centers in Italy. Cost data were collected relating to the 12 months
      preceding the enrollment time (T0), and subsequently 3 months after the T0 time
      (+/-20 days) through a case report form designed to collect the relevant
      information on the costs incurred during the period considered. The data for all
      patients were analyzed through multivariate analysis on the main parameters.
      RESULTS: We enrolled 128 patients equally divided between males and females, with
      a mean age of 13 years (minimum, 0; maximum, 29). Diagnosis was mostly postnatal,
      with 64 cases diagnosed at birth and 33 cases diagnosed subsequently. The lesion
      severity levels, as defined in the inclusion criteria, were walking (52
      patients); walking with simple orthoses (33 patients); walking with complex
      orthoses (16 patients); and nonwalking, (25 patients). The anatomic type
      identified is open SB in most cases (84 patients), followed by closed SB (37
      patients) and SB occulta (3 patients). The most significant cost per year was for
      assistive devices, for a total of 4307.00 ?, followed by hospitalization (907.00
      ?), examinations (592.00 ?), and drug therapy (328.00 ?). Cost breakdown by age
      range shows that the highest costs are incurred in the 0-4 age range. The highest
      cost was for cases of open SB (12,103.00 ?). The cost/degree of severity ratio
      showed that the highest cost was for nonwalking patients (14,323.00 ?), followed
      by patients walking with complex orthoses (13,799.00 ?). CONCLUSION: The data
      from this study show that the mean total cost for a patient with SB was 11,351.00
      ? per year. Based on data provided by the Italian Institute of Health, we can
      estimate a total annual social cost of about 60 million Euros per year for SB in
      Italy. Cost of illness was correlated with age and degree of severity of SB.

PMID- 23861591
TI  - The GAy MEn Sex StudieS: erectile dysfunction among Belgian gay men.
AB  - AIM: To determine the prevalence of erectile dysfunction (ED) in a sample of the
      Belgian men who have sex with men (MSM) population, and to assess the relevance
      of major predictors such as age, relationship, and education. We investigated the
      use of phosphodiesterase type 5 (PDE5) inhibitors among Belgian MSM. METHODS: An
      internet-based survey on sexual behavior and sexual dysfunctions, called GAy MEn
      Sex StudieS (GAMESSS), was administered to MSM, aged 18 years or older, between
      the months of April and December 2008. The questionnaire used was a compilation
      of the Kinsey's Heterosexual-Homosexual Rating Scale, Erection Quality Scale
      (EQS), and the shortened version of the International Index of Erectile Function
      (IIEF-5). RESULTS: Of the 1752 participants, 45% indicated having some problems
      getting an erection. In this group of MSM, 71% reported mild ED; 22% mild to
      moderate ED; 6% moderate ED; and 2% severe ED. Independent predictors for the
      presence of ED were: age (odds ratio [OR] = 1.04, P < 0.0001), having a steady
      relationship (OR = 0.59, P < 0.0001), frequency of sex with their partner (OR =
      1.22, P < 0.0001), versatile sex role (OR = 1.58, P = 0.016), passive sex role
      (OR = 3.12, P < 0.0001), problems with libido (OR = 1.15, P = 0.011), ejaculation
      problems (OR = 1.33, P < 0.0001), and anodyspareunia (OR = 0.87, P < 0.0001). Ten
      percent of the Belgian MSM used a PDE5 inhibitor (age 43 +/- 11 years; mean +/-
      standard deviation) and 83% of them were satisfied with the effects. "Street
      drugs" were used by 43% of MSM to improve ED. CONCLUSION: Forty-five percent of
      participating Belgian MSM reported some degree of ED and 10% used a PDE5
      inhibitor to improve erections. Older MSM reported more ED. MSM, who were in a
      steady relationship or frequently had sex with a partner, reported less ED. MSM
      with ejaculation problems indicated having more ED.

PMID- 23861592
TI  - Lithium intoxication and nephrogenic diabetes insipidus: a case report and review
      of literature.
AB  - Lithium is one of the drugs used widely in the treatment of mood disorders.
      However, it has a very narrow therapeutic index and side effects can be seen in
      many organ systems, one of which affects the kidneys. We can see varying degrees
      of renal damage associated with acute or chronic lithium use. Lithium
      intoxication is diagnosed by a rise in the serum lithium concentration, but it
      must be remembered that serum levels and clinical findings do not always overlap.
      Treatment of lithium intoxication varies according to the clinical findings.
      There are various ways of treating lithium intoxication, but there is no specific
      antidote. The purpose of treatment is to remove the toxin from the body. Here we
      report a patient who was treated for lithium intoxication and developed diabetes
      insipidus during follow-up, and discuss the relevant literature. 

PMID- 23861593
TI  - Two-dimensional and Doppler echocardiographic evaluation of patients presenting
      at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria: a
      prospective study of 2501 subjects.
AB  - BACKGROUND: Echocardiography remains a key noninvasive cardiac investigative tool
      in the management of patients, especially in a developing economy like Nigeria.
      In this study, we investigated the indications for transthoracic echocardiography
      and spectrum of cardiac disease found in patients referred to our cardiac unit
      for echocardiography. METHODS: A prospective two-dimensional, pulsed, continuous,
      and color-flow Doppler echocardiographic evaluation was done using the
      transthoracic approach in 2501 patients over an eight-year period. Univariate
      data analysis was performed for mean age, gender, clinical indications, and
      diagnoses. RESULTS: The subject age range was less than 12 months to 97 years
      (mean 52.39 years). There were 1352 (54.06%) males and 1149 (45.94%) females. The
      most common indication for echocardiography was hypertension (52.1%) followed by
      congestive cardiac failure (13.9%). Others were for screening (6.1%), arrhythmias
      (5%), cerebrovascular disease (5%), chest pain (3.3%), chronic kidney disease
      (3.2%), congenital heart disease (2.6%), cardiomyopathy (1.8%), rheumatic heart
      disease (1.7%), diabetes mellitus (1.3%), thyrocardiac disease (1.2%), ischemic
      heart disease (1.2%), and pericardial disease (1.1%). The echocardiographic
      diagnosis was hypertensive heart disease in 59.4% of subjects and normal in
      14.1%. Other echocardiographic diagnoses included rheumatic heart disease (3.1%),
      congenital heart disease (2.1%), cardiomyopathy (1.7%), pericardial disease
      (1.1%), and ischemic heart disease (0.1%). CONCLUSION: Hypertension and its
      cardiac complications is the most common echocardiographic indication and
      diagnosis at our unit.

PMID- 23861594
TI  - Cryptogenic transient ischemic attack after nose blowing: association of huge
      atrial septal aneurysm with patent foramen ovale as potential cause.
AB  - Association of atrial septal aneurysm (ASA) with patent foramen ovale (PFO) is
      considered an important risk factor for cardioembolism frequently forwarding
      paradoxical embolism in patients with cryptogenic or unexplained cerebral
      ischemic events. We herein describe the case of a 69-year-old male patient
      reporting uncontrolled movements of the right arm due to a muscle weakness,
      slurred speech, and paresthesia in the oral region some seconds after he had
      blown his nose. These neurological symptoms had improved dramatically within a
      few minutes and were completely regressive at admission to our hospital about two
      hours later. On transesophageal echocardiography (TEE) a huge ASA associated with
      PFO was detected. Diagnosis of the large-sized ASA was also confirmed by cardiac
      magnetic resonance imaging. Due to the early complete recovery from his
      neurological symptoms, the patient was diagnosed with a transient ischemic attack
      (TIA). After nine days he was discharged in a good clinical condition under the
      treatment with oral anticoagulation. It is concluded that in cryptogenic or
      unexplained stroke or TIA TEE should always be performed to rule out ASA and PFO
      as potential sources for paradoxical embolism in those inconclusive clinical
      situations. 

PMID- 23861595
TI  - Ultrasound-guided transversus abdominis plane injection with computed tomography
      correlation: a cadaveric study.
AB  - BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) injections are
      increasingly being used as an alternative to traditional perioperative analgesia
      in the abdominal region. With the use of a "blind" TAP block technique, these
      procedures have had variable success in cadaver and in vivo studies. For more
      accurate injection with the intended medication, ultrasound guidance allows
      visualization of the correct layer of the abdominal wall planes in which the
      thoracolumbar nerves reside. OBJECTIVE: To assess the spread of various volumes
      of contrast placed under live ultrasound guidance into the TAP using computed
      tomography (CT). METHODS: Four TAP blocks were performed on 2 fresh frozen
      cadaver torsos with predetermined contrast volumes of 5, 10, 15, or 20 mL. A CT
      scan of the cadaver was then performed and interpreted by a musculoskeletal
      radiologist. This cadaver study was carried out at a tertiary care academic
      medical center. RESULTS: Cranial-caudal spread of injected contrast correlated
      with increasing injectate volume and was roughly 1 vertebral level (end plate to
      end plate) for the 5 mL injection and 2 vertebral levels for the 10, 15, and 20
      mL injections. However, the degree of injectate spread may be different for live
      patients than for cadavers. CONCLUSION: This study helps further the
      understanding of injectate spread following ultrasound-guided TAP injections.
      Specifically, it suggests that 15 mL provides additional cranial-caudal spread
      and may be an optimal volume of anesthesia.

PMID- 23861596
TI  - Safety and efficacy of an add-on therapy with curcumin phytosome and piperine
      and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated
      with dexibuprofen.
AB  - We conducted an 8-week, open, randomized controlled clinical trial on 141
      subjects affected by neuropathic pain to investigate the role of an adjunctive
      therapy added to the administration of dexibuprofen (400 mg twice a day) and
      based on a multi-ingredient formula (Lipicur), consisting of lipoic acid plus
      curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica,
      lumbar disk herniation, and/or lumbar canal stenosis (96 subjects), or with
      carpal tunnel syndrome (45 subjects). A total of 135 participants completed the
      study. Treatment with the multi-ingredient formula (Lipicur) reduced neuropathic
      pain by more than 66% in both conditions (subjects with lumbar sciatica and with
      carpal tunnel syndrome), and these reductions were statistically significant.
      Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy
      with only lipoic acid has not shown any significant results. On the basis of its
      safety and efficacy, Lipicur could be considered an effective complementary
      therapy to be added to conventional treatments to achieve better efficacy in
      reducing neuropathic pain. 

PMID- 23861597
TI  - Serous endometrial intraepithelial carcinoma: a case series and literature
      review.
AB  - BACKGROUND: Minimal uterine serous cancer (MUSC) or serous endometrial
      intraepithelial carcinoma (EIC) has been described by many different names since
      1998. There have been very few cases reported in literature since EIC/MUSC was
      recognized as a separate entity. The World health Organization (WHO)
      Classification favors the term serous EIC. Although serous EIC is confined to the
      uterine endometrium at initial histology diagnosis, a significant number of
      patients could have distal metastasis at diagnosis, without symptoms. Serous EIC
      is considered as being the precursor of uterine serous cancer (USC), but pure
      serous EIC also has an aggressive behavior similar to USC. It is therefore
      prudent to have an accurate diagnosis and appropriate surgical staging. There are
      very few published articles in literature that discuss the pure form of serous
      EIC. The aim of this series is to share our experience and review evidence for
      optimum management of serous EIC. PATIENTS AND METHODS: We report a series of
      five women treated in our institute in the last 3 years. We reviewed the relevant
      literature on serous EIC and various management strategies, to recommend best
      clinical practice. CONCLUSION: Pure serous EIC is a difficult histopathological
      diagnosis, which requires ancillary immunohistochemical staining. It can have an
      aggressive clinical behavior with early recurrence and poor survival. Optimum
      surgical staging, with appropriate adjuvant treatment, should be discussed when
      treating these patients.

PMID- 23861599
TI  - Concepts of comorbidities, multiple morbidities, complications, and their
      clinical epidemiologic analogs.
AB  - The proportion of older people in the world population is expected to increase
      rapidly during the upcoming decades. Consequently, the number of patients with
      multimorbidity will increase dramatically. In epidemiologic research, the
      concepts of multimorbidity, comorbidity, and complications have been confusing,
      and some of these concepts are used interchangeably. In this commentary, the
      authors propose a clear terminology for clinical concepts describing different
      aspects of multimorbidity and elucidate the relationship between these clinical
      concepts and their epidemiologic analogs. Depending on whether a study uses
      causal or predictive models, a proper distinction between concepts of
      multimorbidity is important. It can be very difficult to separate complications
      of the index disease under study from comorbidity. In this context, use of
      comorbidity indices as confounding scores should be done with caution. Other
      methodologic issues are type, duration, severity, and number of comorbidities
      included in the ascertainment methods, as well as sources included in the
      research. Studies that recognize these challenges have the potential to yield
      valid estimates of the comorbidity burden and results that can be compared with
      other studies. 

PMID- 23861598
TI  - When to perform positron emission tomography/computed tomography or radionuclide
      bone scan in patients with recently diagnosed prostate cancer.
AB  - Skeletal metastases are very common in prostate cancer and represent the main
      metastatic site in about 80% of prostate cancer patients, with a significant
      impact in patients' prognosis. Early detection of bone metastases is critical in
      the management of patients with recently diagnosed high-risk prostate cancer:
      radical treatment is recommended in case of localized disease; systemic therapy
      should be preferred in patients with distant secondary disease. Bone scintigraphy
      using radiolabeled bisphosphonates is of great importance in the management of
      these patients; however, its main drawback is its low overall accuracy, due to
      the nonspecific uptake in sites of increased bone turnover. Positron-emitting
      radiopharmaceuticals, such as fluorine-18-fluorodeoxyglucose, choline-derived
      drugs (fluorine-18-fluorocholine and carbon-11-choline) and sodium fluorine-18
      fluoride, are increasingly used in clinical practice to detect metastatic spread,
      and particularly bone involvement, in patients with prostate cancer, to reinforce
      or substitute information provided by bone scan. Each radiopharmaceutical has a
      specific mechanism of uptake; therefore, diagnostic performances may differ from
      one radiopharmaceutical to another on the same lesions, as demonstrated in the
      literature, with variable sensitivity, specificity, and overall accuracy values
      in the same patients. Whether bone scintigraphy can be substituted by these new
      methods is a matter of debate. However, greater radiobiological burden, higher
      costs, and the necessity of an in-site cyclotron limit the use of these positron
      emission tomography methods as first-line investigations in patients with
      prostate cancer: bone scintigraphy remains the mainstay for the detection of bone
      metastases in current clinical practice. 

PMID- 23861601
TI  - Patient considerations in the use of tapentadol for moderate to severe pain.
AB  - Poorly controlled acute and chronic pain can increase morbidity, impair quality
      of life and prolong disability. Over 80 percent of post surgical patients report
      moderate to severe uncontrolled postoperative pain. Over-reliance on potent
      opioid agonists can lead to several opioid related side effects such as
      gastrointestinal intolerability, respiratory depression and cognitive impairment.
      A recently approved dual acting central analgesic tapentadol may offer improved
      tolerability over traditional opioid agonists while having multimodal opioid and
      nonopioid analgesic benefits. Tapentadol, classified by the US Food and Drug
      Administration as a class 2 opioid, is currently marketed in the United States as
      immediate release (IR) NUCYNTA(r) for moderate to severe acute pain in tablets of
      50 mg, 75 mg, and 100 mg, and as extended release (ER) NUCYNTA ER(r) for the
      treatment of chronic moderate to severe pain in tablets of 50 mg, 100 mg, 150 mg,
      200 mg, and 250 mg. Tapentadol is a low affinity mu opioid receptor agonist and a
      norepinephrine reuptake inhibitor. Tapentadol has no active metabolites and this
      property makes it useful in patients with hepatic and renal failure. Clinical
      trials with tapentadol IR showed that there was improved gastrointestinal
      tolerability and similar pain relief as compared to oxycodone IR. Tapentadol ER
      allows for twice daily dosing. Clinical trials showed that tapentadol ER could
      effectively relieve moderate to severe chronic pain and was associated with
      significantly fewer gastrointestinal adverse effects as compared to oxycodone
      controlled release. Tapentadol ER is indicated and has Food and Drug
      Administration approval for the treatment of chronic painful diabetic neuropathy.
      The most common side effects of tapentadol are nausea (30%), vomiting (18%),
      dizziness (24%), and somnolence (15%). Tapentadol, due to its potential
      synergistic effects on norepinephrine levels, is contraindicated in patients who
      have taken monoamine oxidase inhibitors within the last 14 days. Caution has to
      be exercised with the use of tapentadol IR and tapentadol ER in the presence of
      other central nervous system depressants such as neuroleptics, opioids, illicit
      drugs, muscle relaxants, sedatives, and anxiolytics. 

PMID- 23861602
TI  - HPV prevalence at enrollment and baseline results from the Carolina Women's Care
      Study, a longitudinal study of HPV persistence in women of college age.
AB  - BACKGROUND: Cervical cancer, a rare outcome of high-risk human papillomavirus
      (HPV) infection, disproportionately affects African American women, who are about
      twice more likely than European American women to die of the disease. Most
      cervical HPV infections clear in about one year. However, in some women HPV
      persists, posing a greater risk for cervical dysplasia and cancer. The Carolina
      Women's Care Study (CWCS) was conducted to explore the biological, genetic, and
      lifestyle determinants of persistent HPV infection in college-aged European
      American and African American women. This paper presents the initial results of
      the CWCS, based upon data obtained at enrollment. METHODS: Freshman female
      students attending the University of South Carolina were enrolled in the CWCS and
      followed until graduation with biannual visits, including two Papanicolaou tests,
      cervical mucus collection, and a questionnaire assessing lifestyle factors. We
      recruited 467 women, 293 of whom completed four or more visits for a total of
      2274 visits. RESULTS AND CONCLUSION: CWCS participants were 70% European
      American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment,
      32% tested positive for any HPV. HPV16 infection was the most common (18% of
      infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV
      infections. Sixty-four percent of all HPV-positive samples contained more than
      one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We
      found differences between African American and European American women in the
      prevalence of HPV infection (38.1% African American, 30.7% European American) and
      abnormal Papanicolaou test results (9.8% African-American, 5.8% European
      American). While these differences did not reach statistical significance at
      enrollment, as the longitudinal data of this cohort are analyzed, the sample size
      will allow us to confirm these results and compare the natural history of HPV
      infection in college-aged African American and European American women.

PMID- 23861600
TI  - Improved understanding of factors driving methicillin-resistant Staphylococcus
      aureus epidemic waves.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most
      important causes of nosocomial infections worldwide. Since the global spread of
      MRSA in the 1960s, MRSA strains have evolved with increased pathogenic potential.
      Notably, some strains are now capable of causing persistent infections not only
      in hospitalized patients but also in healthy individuals in the community.
      Furthermore, MRSA is increasingly associated with infections among livestock
      associated workers, primarily because of transmission from animals to humans.
      Moreover, many MRSA strains have gained resistance to most available antibiotics.
      In this review, we will present current knowledge on MRSA epidemiology and
      discuss new endeavors being undertaken to understand better the molecular and
      epidemiological underpinnings of MRSA outbreaks. 

PMID- 23861603
TI  - Exercise in obese pregnant women: positive impacts and current perceptions.
AB  - Overweight and obesity have significant implications during pregnancy and
      childbirth. The objective of this review was to provide a comprehensive overview
      of the effect of physical activity on pregnancy outcomes, the change of physical
      activity during pregnancy, and women's perception of being physically active
      during pregnancy, with a particular focus on women who are overweight or obese.
      Many studies have investigated the beneficial effect of exercise during
      pregnancy, including reduced risk of gestational diabetes, preeclampsia, and
      operative birth, in addition to improved cardiovascular function, overall
      fitness, psychological well-being, and mood stability. Benefits for the infant
      include reduced risks of prematurity and improved fetal growth, although there is
      more limited information about longer-term health benefits for both women and
      infants. The existing literature examining physical activity patterns during
      pregnancy has generally focused on women of all body mass index categories,
      consistently indicating a reduction in activity over the course of pregnancy.
      However, the available literature evaluating physical activity during pregnancy
      among women who are overweight or obese is more limited and contradictory. A
      number of studies identified barriers preventing women from being active during
      pregnancy, including pregnancy symptoms, lack of time, access to child care, and
      concerns about their safety and that of their unborn baby. Conversely,
      significant enablers included positive psychological feelings, family influence,
      and receiving advice from health professionals. Very few studies have provided
      insights about perceptions of being active during pregnancy in the overweight and
      obese population. There is a need for a detailed description of physical activity
      patterns during pregnancy in women who are overweight or obese, and more
      randomized trials evaluating exercise interventions for women who are overweight
      or obese, with a focus on clinical outcomes. 

PMID- 23861605
TI  - Introductory editorial.

PMID- 23861604
TI  - Impact of denosumab on bone mass in cancer patients.
AB  - Cancer therapy-induced bone loss (CTIBL) is a form of secondary osteoporosis
      associated with systemic chemotherapy and hormonal ablation therapy. The
      monitoring and treatment of CTIBL is an important component of comprehensive
      cancer care, especially for patients with curable disease and long life
      expectancies. Whereas oral bisphosphonates remain the most commonly used
      therapeutic option for CTIBL, additional treatment options may be required for
      patients who do not respond adequately or are intolerant to bisphosphonates, have
      renal insufficiency, or are receiving treatment with nephrotoxic medications. For
      these patients, denosumab, a monoclonal antibody targeting the receptor activator
      of nuclear factor-kappaB ligand (RANKL), offers an effective and well-tolerated
      alternative. Several recent randomized trials have examined the use of denosumab
      as treatment for CTIBL associated with hormone ablation therapy for breast and
      prostate cancer. Recent data suggest a possible role for RANKL inhibitors in both
      chemoprevention and the prevention of cancer recurrence through direct effects on
      breast tissue and breast cancer stem cells. The outcomes of several international
      Phase III clinical trials currently underway will help clarify the role of
      denosumab in patients undergoing cancer therapy. 

PMID- 23861606
TI  - The effects of fetal surgery on retinopathy of prematurity development.
AB  - BACKGROUND: Fetal surgery is selectively offered for severe or life-threatening
      fetal malformations. These infants are often born prematurely and are thus at
      risk for retinopathy of prematurity (ROP). It is not known whether fetal surgery
      confers an increased risk of developing severe ROP relative to published rates in
      standard premature populations <=37 weeks of age grouped by birth weight (<1500
      grams or >=1500 grams). DESIGN: This is a retrospective chart review. METHODS: We
      reviewed the charts of 137 patients who underwent open fetal/fetoscopic surgery
      from 1996-2004. Surgical indications included twin-twin transfusion syndrome
      (TTTS), myelomeningocele (MMC), congenital diaphragmatic hernia (CDH),
      sacrococcygeal teratoma (SCT), cystic adenomatoid malformation of the lung
      (CCAM), and twin reversed arterial perfusion sequence (TRAP). Of these, 17
      patients had local ROP examination data. Binomial tests were performed to assess
      whether rates of ROP in our fetal/fetoscopic surgery cohort were significantly
      different from published rates. RESULTS: There were 5 patients each with an
      underlying diagnosis of TTTS and MMC, 2 patients each with CDH and TRAP, and 1
      patient each with SCT, CCAM, and mediastinal teratoma. The mean gestational age
      at surgery was 23(4)/7 +/- 2(3)/7 weeks, mean gestational age at birth was 30 +/-
      2(5)/7 weeks, and mean birth weight was 1449 +/- 510 grams (610-2485). Compared
      to published rates of ROP and threshold ROP, our fetal surgery patients had
      significantly higher rates of ROP and threshold ROP in both the <1500 grams and
      the >=1500 grams group (all p-values < 0.05). CONCLUSIONS: Fetal/fetoscopic
      surgery appears to significantly increase the rate of ROP and threshold ROP
      development. Greater numbers are needed to confirm these observations.

PMID- 23861607
TI  - Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following
      Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal
      Uptake of Acyclovir Following Oral Dosing.
AB  - OBJECTIVE: To delineate the plasma pharmacokinetics and determine the corneal
      uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in
      rats. METHODS: Male Sprague-Dawley rats were used for the study. Pharmacokinetics
      of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D
      valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were
      administered intravenously as a bolus via jugular vein cannula and orally by
      gavage. Samples were purified by protein precipitation method and analyzed by LC
      MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin.
      Corneal uptake studies of LDACV and LACV were studied following oral
      administration. RESULTS: Following i.v. administration, the area under the curve
      (AUC) in MUM*min of generated ACV was in the order of LACV > LDACV > DLACV
      indicating their rate of metabolism. The AUC values of total drug obtained in the
      systemic circulation after oral administration LACV and LDACV were 1077.93 +/-
      236.09 and 1141.76 +/- 73.67 MUM*min, respectively. DLACV exhibited poor oral
      absorption. Cmax (MUM) and AUC of the intact prodrug obtained in the systemic
      circulation following oral administration of LDACV were almost 4-5 times higher
      than LACV. Moreover, concentrations achieved in the cornea after oral
      administration of LDACV were almost two times of LACV. CONCLUSIONS: LDACV
      increased both the oral bioavailability and subsequent in vivo corneal uptake of
      ACV. Hence, LDACV can be considered as the most promising drug candidate for
      delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis
      after oral administration.

PMID- 23861608
TI  - Anterior Chamber-Associated Immune Deviation (ACAID): An Acute Response to Ocular
      Insult Protects from Future Immune-Mediated Damage?
AB  - The "immune privilege" that inhibits immune defense mechanisms that could lead to
      damage to sensitive ocular tissue is based on the expression of immunosuppressive
      factors on ocular tissue and in ocular fluids. In addition to this environmental
      protection, the injection of antigen into the anterior chamber or infection in
      the anterior chamber induces a systemic suppression of potentially damaging cell
      mediated and humoral responses to the antigen. Here we discuss evidence that
      suggests that Anterior Chamber-Associated Immune Deviation (ACAID)(a) is
      initiated by an ocular response to moderate inflammation that leads to a systemic
      immunoregulatory response. Injection into the anterior chamber induces a rise in
      TNF-alpha and MCP-1 in aqueous humor and an infiltration of circulating F4/80(+)
      monocytes that home to the iris. The induction of ACAID is dependent on this
      infiltration of circulating monocytes that eventually emigrate to the thymus and
      spleen where they induce regulatory T cells that inhibit the inductive or
      effector phases of a cell-mediated immune response. ACAID therefore protects the
      eye from the collateral damage of an immune response to infection by suppressing
      a future potentially damaging response to infection. 

PMID- 23861609
TI  - Retinal ganglion cell loss in diabetes associated with elevated homocysteine.
AB  - A number of studies have suggested that homocysteine may be a contributing factor
      to development of retinopathy in diabetic patients based on observed correlations
      between elevated homocysteine levels and the presence of retinopathy. The
      significance of such a correlation remains to be determined, and potential
      mechanisms by which homocysteine might induce retinopathy have not been well
      characterized. Ganapathy and colleagues1 used mutant mice that have endogenously
      elevated homocysteine levels due to heterozygous deletion of the cystathionine
      beta-synthase gene to examine changes in retinal pathology following induction of
      diabetes. Their finding that elevated homocysteine levels hastens loss of cells
      in the retinal ganglion cell layer suggests that toxicity to ganglion cells may
      warrant further investigation as a potential mechanism of homocysteine enhanced
      susceptibility to diabetic retinopathy. 

PMID- 23861610
TI  - Spectral Domain OCT Documented Resolution of Pseudophakic Cystoid Macular Edema
      after Intravitreal Triamcinolone.
AB  - Cystoid macular edema (CME) is an important cause of visual loss after cataract
      surgery. Treatment is usually with topical anti-inflammatory agents, with anti
      vascular endothelial growth factor agents and steroids used intravitreally in
      resistant cases. Even though time-domain Stratus OCT can quantify the macular
      thickness, it cannot prognosticate visual outcomes due to the poor resolution of
      images, especially the outer segment-inner segment junction. Spectral-domain OCT
      (SD-OCT) by its ability to acquire large number of images in a short span of time
      provides high resolution cross-sectional images of the retina, which not only
      highlights the underlying pathological changes, but in addition can prognosticate
      visual recovery. We describe pre and post SD-OCT features of a case of refractory
      CME who was treated with intravitreal triamcinolone actetonide. 

PMID- 23861611
TI  - The use of topical tacrolimus 0.1% skin ointment for anterior segment conditions:
      a case series.
AB  - Tacrolimus (FK 506) is a macrolactam derivative with immunomodulatory and anti
      inflammatory activity. Topical tacrolimus 0.03% has been used for inflammatory
      conditions of the anterior segment. This article adds to the literature on the
      off-license application of tacrolimus ointment, by describing the safe and
      effective use of the higher strength of 0.1% topical tacrolimus skin ointment in
      four patients. To our knowledge this is the first report of topical tacrolimus
      0.1% ointment applied to the conjunctival sac for the treatment of atopic
      keratoconjunctivitis, vernal keratoconjunctivitis and the post-operative
      management of trabeculectomy and graft rejection in steroid responders. 

PMID- 23861612
TI  - Anti-inflammatory and Antihistaminic Study of a Unani Eye Drop Formulation.
AB  - The Unani eye drop is an ophthalmic formulation prepared for its beneficial
      effects in the inflammatory and allergic conditions of the eyes. In the present
      study, the Unani eye drop formulation was prepared and investigated for its anti
      inflammatory and antihistaminic activity, using in vivo and in vitro experimental
      models respectively. The Unani eye drop formulation exhibited significant anti
      inflammatory activity in turpentine liniment-induced ocular inflammation in
      rabbits. The preparation also showed antihistaminic activity in isolated guinea
      pig ileum. The anti-inflammatory and antihistaminic activity of eye drop may be
      due to presence of active ingredients in the formulation. Although there are many
      drugs in Unani repository which are mentioned in classical books or used in Unani
      clinical practice effectively in treatment of eye diseases by various Unani
      physicians. Inspite of the availability of vast literature, there is a dearth of
      commercial Unani ocular preparations. So, keeping this in mind, the eye drop
      formulation was prepared and its anti-inflammatory and antihistaminic activity
      was carried out in animal models. Thus, in view of the importance of alternative
      anti-inflammatory and antiallergic drugs, it becomes imperative to bring these
      indigenous drugs to the front foot and evaluate their activities. 

PMID- 23861613
TI  - Small Neutral Amino Acid Ester Prodrugs of Acyclovir Targeting Amino Acid
      Transporters on the Cornea: Possible Antiviral Agents Against Ocular HSV-1
      Infections.
AB  - The aim of this study was to characterize the affinity and permeability patterns
      of the amino acid ester prodrugs of acyclovir (ACV), L-alanine-ACV (AACV), L
      serine-ACV (SACV), L-serine-succinate-ACV (SSACV) and L-cysteine-ACV (CACV) on
      rabbit primary corneal epithelial cell culture (rPCEC) and on rabbit cornea.
      Amino acid prodrugs of acyclovir, AACV, SACV, SSACV and CACV were synthesized in
      our laboratory. Chemical hydrolysis in aqueous buffer, enzymatic hydrolysis in
      corneal homogenates and transport across freshly excised rabbit cornea of these
      prodrugs were studied. SSACV inhibited the uptake of [(3)H] L-alanine on rPCEC
      and across the intact rabbit cornea. Lineweaver-Burk plot transformation revealed
      competitive inhibition between L-alanine and SSACV. In corneal tissue homogenate,
      the half lives of SSACV, SACV and CACV (t1/2) were observed to be 3.5 +/- 0.4,
      9.2 +/- 0.6 and 1.8 +/- 0.1 hr respectively, whereas AACV was readily converted
      to the active parent drug acyclovir exhibiting complete degradation before 5 min.
      Interestingly translocation of SACV across cornea was inhibited in the presence
      of 5 mM arginine (~51%), a specific substrate for cationic transport system and
      in presence of BCH (~38%), a substrate specific for large neutral amino acid
      transport system (LAT) or cationic and neutral amino acid transport system
      (B(0,+)). SACV exhibited higher permeability across cornea along with excellent
      antiviral activity against herpes simplex virus (HSV-1) and varicella-zoster
      virus (VZV) in comparison to ACV. Recognition by multiple transporters, stability
      in corneal homogenate and changes in physico-chemical properties contributed to
      the increased permeability of SACV across cornea. 

PMID- 23861614
TI  - The Induction of Circulating, ACAID-Inducing Monocytes Requires CCR2/CCL2
      Dependent Migration of Circulating F4/80(+) Cells into the Anterior Chamber.
AB  - To determine the origin of peripheral blood mononulclear cells (PBMC) that
      activate regulatory T cells in anterior chamber-associated immune deviation
      (ACAID), fluorescein-labeled PBMC were intravenously injected into mice before
      the mice received an intracameral injection of antigen. Six-24 hr after
      intracameral injection, fluorescein-labeled PBMC increased in the iris. Twenty
      four-48 hr labeled cells decreased in the iris and increased in the thymus and
      spleen. The entry of the labeled PBMC into the anterior chamber and subsequent
      production of PBMC that transfer ACAID required the expression of CCR2 by the
      PBMC and the production of the chemokine CCL2 by the recipient of the PBMC. The
      results suggest that the intracameral injection of antigen induces i) the
      infiltration of F4/80(+) PBMC into the AC, ii) where these PBMC are converted to
      a regulatory phenotype, and iii) recirculate to activate T cells that suppress
      cell-mediated immunity. 

PMID- 23861615
TI  - Isolated bilateral trigeminal neuropathy in sarcoidosis presenting with
      neurotrophic corneal ulcers.
AB  - Sarcoidosis is a multisystem granulomatous disease that may affect various
      organs. Nevertheless, involvement of the trigeminal nerve is exceedingly
      uncommon. This report presents a rare case of isolated bilateral trigeminal
      neuropathy presenting with neurotrophic corneal ulcers. The patient was treated
      with topical chloramphenicol and lubricants, as well as botulinum toxin injection
      to the upper eyelid to induce ptosis. Our case illustrates the importance of
      recognizing that bilateral corneal ulceration might be a manifestation of
      sarcoidosis. Physicians should be aware of this rare association, when treating
      sarcoidosis patients with eye related symptoms. 

PMID- 23861616
TI  - Bevasiranib for the treatment of wet, age-related macular degeneration.
AB  - Age- related Macular Degeneration (AMD) is the leading cause of severe visual
      impairment in people 65 years and older in industrialized nations. Exudative, or
      "wet", AMD is a late form of AMD (as distinguished from atrophic, so-called dry,
      AMD) and is responsible for over 60% of all cases of blindness due to AMD. It is
      widely accepted that vascular endothelial growth factor (VEGF) is a key component
      in the pathogenesis of choroidal neo-vascularization (CNV), which is a precursor
      to wet AMD. The current gold-standard for treating wet AMD is the monoclonal
      antibody fragment ranibizumab (trade name Lucentis), which targets VEGF. Other
      agents used to treat wet AMD include pegaptanib (Macugen), bevacizumab (Avastin;
      off-label use), and several other experimental agents. The advent of small
      interfering RNA (siRNA) has presented a whole new approach to inhibiting VEGF.
      This article reviews the status of a novel siRNA-based therapeutic, bevasiranib,
      for the treatment of wet AMD. Bevasiranib is believed to work by down regulating
      VEGF production in the retina. Studies in human cell-lines and animal models have
      shown that VEGF siRNAs are effective in inhibiting VEGF production. Although
      there is a lack of sufficient published data on human studies supporting the use
      of bevasiranib for wet AMD, available data indicates that due to its unique
      mechanism of action, bevasiranib might hold some promise as a primary or adjunct
      treatment for wet AMD. 

PMID- 23861617
TI  - Phototherapeutic keratectomy outcomes in superficial corneal opacities.
AB  - PURPOSE: COMPARE THE EFFECTIVENESS OF PHOTOTHERAPEUTIC KERATECTOMY (PTK) IN
      TREATMENT CORNEAL DYSTROPHIES VERSUS SUPERFICIAL CORNEAL SCARS: visual outcomes,
      recurrence rate and safety profile. METHODS: PTK was performed in 51 eyes of 51
      patients. Data regarding the indications for PTK, ablation depth, symptomatic
      relief, pre-and postoperative best spectacle-corrected visual acuity (BSCVA),
      spherical equivalent changes, recurrence and complications were analyzed. The
      indications for PTK in our study were classified into two categories - group A:
      patients with corneal dystrophies (n = 23) and the other group B (n = 28) with
      other indications. RESULTS: The average age of the patients was 47 years (+/
      16.4). The mean follow up period was 15.16 months (+/-10.01 months). Post
      operatively, there were no significant complications. While the overall BSCVA in
      the patients improved from 20/41 (0.484) to 20/32 (0.645), group A showed
      improvement from 20/35 (0.561) to 20/29 (0.687), as compared to group B in which
      BSCVA improved from 20/47 (0.421) to 20/33 (0.611). The most common indication in
      group A was granular corneal dystrophy (n = 10) and the most common indication in
      group B was post traumatic/infectious corneal scar or opacity (n = 10). Eighty
      six percent (n = 44) of all patients had alleviation of symptoms. Recurrence of
      symptoms was seen in 3 eyes of recurrent corneal erosions which required
      retreatment. CONCLUSION: PTK is a safe and effective procedure. The outcome of
      this study suggests that PTK improves BSCVA. PTK appears to improve ocular
      surface health. Furthermore, PTK can be recommended to most patients with corneal
      dystrophies as a treatment modality prior to other more invasive procedure (viz.
      penetrating keratoplasty).

PMID- 23861618
TI  - Besifloxacin ophthalmic suspension: emerging evidence of its therapeutic value in
      bacterial conjunctivitis.
AB  - OBJECTIVE: To outline the pharmacodynamics, efficacy and safety of besifloxacin
      ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis. QUALITY
      OF EVIDENCE: MEDLINE database was searched to review recent pharmacodynamic and
      clinical studies evaluating besifloxacin and comparing besifloxacin to other
      topical antibiotics for ophthalmic use. Findings were limited to full-text
      articles from clinical journals in the English language. MAIN MESSAGE: Bacterial
      resistance is a common source for treatment failure in bacterial conjunctivis.
      Besifloxacin, a novel fourth generation synthetic fluoroquinolone is likely to
      show lower resistance rates due to its mechanism of action and its short-term use
      for ocular infections only (decreased systemic exposure). Besifloxacin displays
      improved pharmacodynamic properties compared to other commonly used
      fluoroquinolones and has shown to be efficacious and safe in clinical studies.
      CONCLUSION: Besifloxacin ophthalmic suspension 0.6% provides safe and efficacious
      treatment for bacterial conjunctivitis. The factors leading to bacterial
      resistance are diminished, which allows besifloxacin to be a favorable treatment
      option.

PMID- 23861619
TI  - Tafluprost for the reduction of interocular pressure in open angle glaucoma and
      ocular hypertension.
AB  - Tafluprost is an FP receptor antagonist that has been shown in clinical studies
      in Europe and Japan to be extremely useful in treating elevated intraocular
      pressure and glaucoma. The drug is well tolerated and appears to be at least
      equal in effectiveness and perhaps superior to other protanoids for routine use
      comparison to be superior to other treatments for the elevated IOP as the side
      effects and other related symptomology appear to be less, while maintaining a
      level of pressure control for prolonged periods. 

PMID- 23861620
TI  - Central corneal melting associated with reformulated generic diclofenac in a
      patient with inferior fornix foreshortening.
AB  - PURPOSE: To report a case of corneal melting in a patient with fornix
      foreshortening being treated with reformulated generic diclofenac. METHODS: Case
      report. RESULTS: An asymptomatic 76-year old man presented with central corneal
      melting while being treated with reformulated generic diclofenac. This
      formulation did not contain the vitamin E derivative, tocophersolan, which has
      been felt to contribute to corneal melting associated with generic diclofenac in
      the past. Other factors for corneal melting included multiple medication use and
      altered forniceal architecture, but did not include previous corneal or cataract
      surgery. Following discontinuation of the topical medications and temporary
      tarsorrhapy, the defect reepithelialized. CONCLUSION: In patients with a
      compromised ocular surface, reformulated generic diclofenac has the potential to
      cause corneal melting without prior cataract or refractive surgery. Use should
      not be indiscriminate or without close supervision.

PMID- 23861621
TI  - Severe acute endogenous endophthalmitis with Staphylococcus epidermidis in a
      systemically well patient.
AB  - Endogenous endophthalmitis is a devastating intraocular infection caused by
      haematogenous spread of bacteria or fungi, usually in people with immune
      deficiency. This case report is unusual as a systemically well patient with
      normal immune function and no identifiable locus of infection rapidly developed a
      fulminant endogenous endophthalmitis from an organism which does not usually
      produce aggressive virulence determinants. Endogenous bacterial endophthalmitis
      is an ongoing diagnostic and therapeutic dilemma for ophthalmologists as it is
      relatively rare, often initially presents as uveitis, and requires a high index
      of suspicion for prompt diagnosis and treatment. The treatment of endogenous
      endophthalmitis is still controversial due to a lack of clinical trials.
      Potential treatments include systemic antibiotics, peri-ocular injections,
      intravitreal injection of antibiotics and possibly corticosteroids, pars plana
      vitrectomy, or a combination of some of these. 

PMID- 23861623
TI  - Circulating reactive oxidant causes apoptosis of retinal pigment epithelium and
      cone photoreceptors in the mouse central retina.
AB  - Reactive oxidants damage the retinal pigment epithelium (RPE), which is required
      for viability of overlying photoreceptors. Smoking which leads to chronic
      accumulation of reactive oxidants in the circulation is linked to age-related
      macular degeneration (AMD) where RPE death is seen along with photoreceptor loss
      in the central macular region of the retina. It is unclear why this damage is
      concentrated in the central retina. We asked whether circulating oxidant might
      specifically target the central retina. Mice were administered the classic
      reactive oxidant iodate through tail vein injection, and visual acuity was
      followed by optokinetic response. Histology and apoptosis was examined by H&E and
      immunostaining. Iodate indeed selectively damaged the central retina, and this
      damage was highlighted by early apoptosis of RPE in the central retina followed
      by apoptosis of photoreceptors adjacent to the region of RPE loss-cones were lost
      preferentially. The pattern and extent of this damage was independent of exposure
      to light. We then conclude that circulating oxidant is sufficient to selectively
      damage the central retina highlighted by sequential apoptosis of RPE and
      photoreceptors, with cones being the most sensitivity to this RPE loss. 

PMID- 23861622
TI  - A European perspective on topical ophthalmic antibiotics: current and evolving
      options.
AB  - BACKGROUND: Eye infections can be vision-threatening and must be treated
      effectively by appropriate and safe use of topical ophthalmic anti-infectives.
      This review will essentially consider the current and evolving treatment options
      for the various types of bacterial eye infections. Ocular surface bacterial
      infections affect subjects of all ages with a high frequency in newborns and
      children. METHODS: This article presents a review of the peer-reviewed published
      scientific literature in order to define the well-established uses of anti
      infective eye drops in the field of ocular infections. A comprehensive search of
      the recent published literature including topical ophthalmic anti-infectives
      effective in bacterial ocular infections was performed. Clinical studies provide
      relevant data concerning the characteristics and clinical efficacy of
      antibacterial eye drops in ocular anterior segment infections or for
      perioperative prophylaxis. Publications were included to cover the current
      options of antibacterial eye drops available in Europe. RESULTS: Several recent
      publications identified effective topical ocular antibacterials requiring a
      reduced dose regimen and a short treatment course. Additional literature reviewed
      included data on novel perioperative prophylaxis, indications for topical
      fortified antibiotics and innovative research including the risk of resistance.
      CONCLUSIONS: Safe and effective topical antibiotic eye drops for the treatment
      and prevention of ocular infections must be adapted to the type of bacteria
      suspected. Usual topical antimicrobials should be replaced by more recent and
      more effective treatments. The use of highly effective fluoroquinolones should be
      reserved for the most severe cases to avoid resistance. Short treatment courses,
      such as azithromycin, can be easily used in children, thereby improving quality
      of life.

PMID- 23861624
TI  - Radiographic and histological findings in an atypical orbital myxoma.
AB  - Myxomas are rare neoplasms of mesenchymal origin. Diagnostic evaluation requires
      histopathological confirmation. We report a rare case of atypical orbital myxoma
      with radiographic and histopathological correlation. 

PMID- 23861625
TI  - Low Bone Mass is Associated with Increased Carotid Intima Media Thickness in Men
      with Type 2 Diabetes Mellitus.
AB  - Osteoporosis and atherosclerosis share common risk factors and the association of
      low bone mass with increased cardiovascular morbidity and mortality has been
      demonstrated in some studies. Nevertheless, most studies have been focused on
      women and only a few on individuals with type 2 diabetes mellitus (T2DM). The
      measurement of carotid intimal-medial thickness (CIMT) is able to detect early
      atherosclerotic changes and is a predictive marker of cardiovascular events. The
      aim of this study was to assess the CIMT and its relationship with bone mineral
      density (BMD) (in the femoral neck (FN) and lumbar spine (LS)) in men with T2DM.
      We conducted a cross-sectional study with 24 men with T2DM (aged 61 +/- 6.4
      years) and evaluated metabolic factors, bone densitometry values, and CIMT
      measured using B-mode Logic-E ultrasound machine. More than 5 years since the
      diagnosis of T2DM had passed in 75% of the patients, 41.6% were in statin use,
      mean body mass index (BMI) was 28.1 +/- 3.4 kg/m(2), abdominal circumference (AC)
      97.8 +/- 8.4 cm, systolic blood pressure (SBP) 143.8 +/- 18.3 mmHg, diastolic
      blood pressure (DBP) 85.8 +/- 12.3 mmHg, HbA1C 7.5% +/- 1.3%, Triglycerides 141.7
      +/- 73 mg/dL, LDL-cholesterol 103.3 +/- 35.9 mg/dL, HDL-cholesterol 41.6 +/- 11.6
      mg/dL. The patients were stratified into groups according to BMD. The group with
      normal BMD at FN had mean CIMT of 0.7 mm and the group with low bone mass
      (osteopenia or osteoporosis) had CIMT of 0.86 mm (P = 0.007). In addition, there
      were no significant differences between groups regarding age, duration of T2DM,
      BMI, AC, SBP, DBP, statin use, smoking, HbA1C, cholesterol, or triglycerides. Our
      data demonstrate a negative association between BMD at the FN and CIMT in type 2
      diabetic men, which was unrelated to the traditional risk factors for
      atherosclerotic disease and degree of diabetes control. 

PMID- 23861626
TI  - Nursing Roles within a Stroke Telemedicine Network.
AB  - Time sensitive acute stroke treatments and the growing shortage of vascular
      neurologists compound to create a gap in the delivery of care to meet the
      American Stroke Association guidelines in underserviced regions. Audio/video
      consultation (telemedicine), which has been evolving since the late 1990's, is a
      putative solution. While telemedicine can serve as a valuable facilitative tool,
      the telestroke consultation is only one piece of a complex collaboration between
      hub and spoke environments and clinical personnel. The growing use of
      telemedicine in stroke offers more opportunities for all nurses to participate in
      the continuum of cerebrovascular disease care. A review of this collaboration
      will include but will not be limited to: algorithms of the acute stroke
      evaluation, hub and spoke staff meetings, stroke education for spoke staff, and
      patient follow-up post acute treatment. Our team's telemedicine experience,
      utilizing research, education, and clinical practice, will be described. 

PMID- 23861627
TI  - Decreased Serum Cu/Zn SOD Associated with High Copper in Children with Attention
      Deficit Hyperactivity Disorder (ADHD).
AB  - AIM: To assess serum Cu/Zn SOD (Superoxide Dismutase) concentration in children
      with ADHD and evaluate its possible relationship to Cu and Zn levels. SUBJECTS
      AND METHODS: Serum from 22 children with ADHD and 20 healthy control children
      without ADHD and 19 autistic children without ADHD were tested for Cu/Zn SOD
      using ELISAs and levels of serum Cu and Zn using inductively-coupled plasma-mass
      spectrometry. RESULTS: Serum Cu/Zn SOD levels of ADHD children were significantly
      lower than age and gender matched healthy non-ADHD controls (P < 0.001). Serum
      Cu/Zn SOD of ADHD children was significantly lower in individuals with high serum
      copper (P = 0.024). There was no significant correlation between Cu/Zn SOD levels
      and Zinc or Cu/Zn in ADHD individuals. DISCUSSION: These results suggest an
      association between Cu/Zn SOD serum levels and ADHD, particularly ADHD children
      with high serum copper.

PMID- 23861628
TI  - The safety and efficacy of methylphenidate and dexmethylphenidate in adults with
      attention deficit/hyperactivity disorder.
AB  - OBJECTIVE: To review the literature on the safety and efficacy of
      methylphenidate, OROS-methylphenidate, methylphenidate ER, and dexmethylphenidate
      in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). To analyze the
      effects of different doses of methylphenidate, it's various formulations, and
      methylphenidate on efficacy and safety in this population. DATA SOURCES:
      Literature retrieval was performed through Pubmed/MEDLINE (Up to May 2010) using
      the terms methylphenidate, dexmethylphenidate, and attention-deficit
      hyperactivity disorder. In addition, reference citations from publications
      identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Double-blinded,
      placebo-controlled clinical trials, as well as crossover and open-label trials
      found using the search criteria listed above were included for review. Case
      reports were not included in this review. DATA SYNTHESIS: Attention
      deficit/hyperactivity disorder (ADHD) is a psychiatric condition that is commonly
      seen in children and adolescents, that persists into adulthood for about 50% of
      patients. Methylphenidate and dexmethylphenidate are often prescribed to treat
      the symptoms associated with ADHD. The literature validating the safety and
      efficacy of methylphenidate and dexmethylphenidate in children and adolescents
      with ADHD is substantial. However, the literature specifically addressing the
      safety and efficacy of these medications in the adult population is less
      extensive and prescribing is often anecdotal based on child and adolescent data.
      Understanding the literature regarding methylphenidate and dexmethylphenidate and
      its effects in adults can enhance evidence-based medicine (EBM) and improve
      treatment outcomes. CONCLUSION: Methylphenidate and dexmethylphenidate are safe
      and effective medications to treat the symptoms of ADHD in adults. Based on the
      literature, increased doses are associated with better treatment response with
      moderate safety concerns. The different dosage forms available enable
      individualization of treatment.

PMID- 23861629
TI  - Is persistent visual neglect associated with poor survival?
AB  - BACKGROUND: The association of visual neglect with survival after right
      hemisphere (RH) stroke has received only limited attention. OBJECTIVE: This study
      explores the relationship of visual neglect and its spontaneous recovery to
      survival in a homogenous patient group with first-ever RH stroke. METHODS: Fifty
      one RH stroke patients who suffered an infarct between 1994 and 1997 were
      retrospectively followed for survival until August 31, 2009. Acute-phase
      neurological, neuropsychological and neuroradiological data were studied to
      identify predictors of survival. RESULTS: Twenty-eight patients died during the
      follow-up. Age, education, and poor recovery of visual neglect emerged as
      significant single predictors of death. The best set of predictors for poor
      survival in the multivariate model was poor recovery of visual neglect and low
      education. CONCLUSIONS: Poor recovery of visual neglect is associated with long
      term mortality in RH infarct patients. The follow-up of RH patients'
      neuropsychological performance gives additional information about the prognosis.

PMID- 23861631
TI  - Gabapentin enacarbil: pharmacotherapy of restless legs syndrome.
AB  - Restless Legs Syndrome (RLS) is a prevalent sleep-associated movement disorder
      greatly affecting patients' quality of life (QoL). Several drugs can be used to
      control this condition although the first-line dopamine agents often cause
      adverse effects. Non-dopaminergic drugs such as oral gabapentin (GBP) have been
      more recently advocated. Despite ameliorating RLS symptoms, GBP's pharmacokinetic
      limitations restrict its overall effectiveness. A novel specifically designed
      prodrug, gabapentin enacarbil (GE), has demonstrated successful RLS alleviation
      with a superior pharmacokinetic profile. This review aims to examine the efficacy
      and tolerability of both GBP and GE as pharmacotherapy for RLS. Despite some
      heterogeneity and limitations across research methodologies, GE appears to be a
      potential RLS therapy superior to GBP and other dopaminergic agents. 

PMID- 23861630
TI  - Animal models of autism: an epigenetic and environmental viewpoint.
AB  - Autism is a neurodevelopmental disorder of social behavior, which is more common
      in males than in females. The causes of autism are unknown; there is evidence for
      a substantial genetic component, but it is likely that a combination of genetic,
      environmental and epigenetic factors contribute to its complex pathogenesis.
      Rodent models that mimic the behavioral deficits of autism can be useful tools
      for dissecting both the etiology and molecular mechanisms. This review discusses
      animal models of autism generated by prenatal or neonatal environmental
      challenges, including virus infection and exposure to valproic acid (VPA) or
      stress. Studies of viral infection models suggest that interleukin-6 can
      influence fetal development and programming. Prenatal exposure to the histone
      deacetylase inhibitor VPA has been linked to autism in children, and male VPA
      exposed rats exhibit a spectrum of autistic-like behaviors. The experience of
      prenatal stress produces male-specific behavioral abnormalities in rats. These
      effects may be mediated by epigenetic modifications such as DNA methylation and
      histone acetylation resulting in alterations to the transcriptome. 

PMID- 23861632
TI  - Duloxetine: a review of its safety and efficacy in the management of fibromyalgia
      syndrome.
AB  - Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and
      other associated symptoms including fatigue, insomnia, cognitive/memory problems,
      and even psychological distress. Duloxetine is one of three FDA approved
      medications (the other two being milnacipran and pregabalin) for the treatment of
      FM. It has been demonstrated that FM patients possess low central nervous system
      levels of serotonin and norepinephrine. Duloxetine, which is classified
      pharmacologically as a serotonin-norepinephrine reuptake inhibitor (SNRI), may be
      beneficial for FM patients by increasing these levels. This review will touch
      briefly upon the pathophysiology of FM, diagnostic tools, currently available
      therapeutic options (both pharmacologic and non-pharmacologic), as well as the
      pharmacokinetic/pharmacodynamic properties of duloxetine. In addition, the
      efficacy and safety/tolerability of duloxetine exclusively in FM will be assessed
      through examination of 5 randomized controlled trials, as well as pooled analyses
      of current data. Suggestions for a therapeutic niche for duloxetine in FM are
      discussed based on a presentation of the characteristics of duloxetine. 

PMID- 23861633
TI  - Predictors of discharge to home after thrombolytic treatment in right hemisphere
      infarct patients.
AB  - BACKGROUND: The aim of the study was to assess the association between
      thrombolysis and length of hospital stay after right hemisphere (RH) infarct, and
      to identify which cognitive functions were predictive of discharge. METHODS: The
      study group consisted of 75 acute RH patients. Thirty-three patients had
      thrombolysis. Neuropsychological examinations were performed within 11 days of
      stroke onset. The cognitive predictors were visual neglect, visual memory, visual
      search and reasoning and visuoconstructive abilities. The outcome variable was
      time from stroke to discharge to home. RESULTS: Thrombolysis emerged as a
      statistically significant predictor of discharge time in patients with
      moderate/severe stroke (NIHSS >=5). In the total series of patients and in
      patients with mild stroke (NIHSS <5), thrombolysis was not significantly
      associated with discharge time. Milder visuoconstructive defects shortened the
      hospital stay of the whole patient group and of patients with moderate/severe
      stroke. In all patient groups, independence in activities of daily living (ADL)
      was a significant single predictor of a shorter hospital stay. The best
      combination of predictors for discharge was independence in ADL in the total
      series of patients and in patients with mild stroke, and thrombolysis and
      independence in ADL in patients with moderate/severe stroke. CONCLUSIONS:
      Thrombolytic treatment was a significant predictor of earlier discharge to home
      in patients with moderate/severe RH infarct, while cognitive functions had less
      predictive power.

PMID- 23861634
TI  - Ziprasidone hydrocloride: what role in the management of schizophrenia?
AB  - BACKGROUND: Since schizophrenia is considered one of the top ten causes of
      disease-related disability in the world, the development of second-generation
      (atypical) antipsychotics (SGAs) has increased the hopes of psychiatrists. SGAs,
      however, cannot be considered a unique pharmacological class since each SGA has
      many complex pharmacologic actions, only some of which are shared with other
      SGAs. Even though manyantipsychotics have similar efficacy on average,
      prescribers may be able to achieve better than average results by considering
      differences in selecting a specific drug for a specific patient. Clinicians know
      that each patient is unique. In order to achieve best outcomes for the individual
      patient, the better therapy is the therapy tailored for the single patient.
      OBJECTIVES: With this article, we provide information on a relatively new
      antipsychotic ziprasidone released in 2001 by Pfizer for the treatment of
      schizophrenia. Compared with other first line atypical antipsychotics ziprasidone
      has a unique profile due to potent interaction with serotonergic receptors and
      lesser action upon alpha1 adrenergic, H1 and M1 antagonist activities. This paper
      describes the development of ziprasidone, its unique properties and its
      metabolically-friendly profile including its receptor binding affinities,
      pharmacokinetics, CNS activity results of clinical efficacy and relevant clinical
      trials. Safety, efficacy and patient preference are also examined. The available
      literature on ziprasidone of the last five years is reviewed.

PMID- 23861635
TI  - Levetiracetam Extended Release as Adjuvant Therapy for the Control of Partial
      onset Seizures.
AB  - Extended release (XR) formulation of levetiracetam (LEV) is approved by the Food
      and Drug Administration as an add-on to other antiepileptic drugs (AEDs) for
      adults with partial onset seizures. This is based on class-I evidence
      demonstrating significant seizure reduction in once daily dosing. Keppra-XR is
      marketed with the brand name of Keppra XR since 2008 (UCB Pharma). Its original
      immediate release (IR) formulation has been in the market since 2000. LEV has a
      unique molecular structure which is chemically unrelated to existing AEDs. The
      precise mechanism of action is unknown. Animal studies showed binding to synaptic
      vesicle protein SV2A, thought to be involved in modulating synaptic
      neurotransmitter release. LEV-IR is proven effective as adjunctive therapy for
      partial-onset seizures, primary generalized tonic-clonic seizures and myoclonic
      seizures. It was shown to be equivalent to carbamazepine as first-line treatment
      for partial-onset seizures. The extended release formulation added advantages
      such as better tolerance and increased compliance. 

PMID- 23861636
TI  - Safety and efficacy of paliperidone extended-release in acute and maintenance
      treatment of schizophrenia.
AB  - Paliperidone, the major active metabolite of risperidone, is a second-generation
      antipsychotic that has been developed as an extended-release (ER) tablet
      formulation that minimizes peak-trough fluctuations in plasma concentrations,
      allowing once-daily administration and constant drug delivery. Paliperidone ER
      has demonstrated efficacy in the reduction of acute schizophrenia symptoms in 6
      week, placebo-controlled, double-blind trials and clinical benefits were
      maintained in the longer-term according to extension studies of up to 52 weeks in
      duration. Compared with quetiapine, paliperidone ER was associated with a more
      rapid symptom improvement. In addition, it was more effective than placebo in the
      prevention of symptom recurrence. Paliperidone ER is generally well tolerated
      with a predictable adverse event profile. Like risperidone, it is associated with
      a dose-dependent risk of extrapyramidal symptoms and prolactin elevation. Short-
      and longer-term studies have indicated a low liability for paliperidone ER to
      cause metabolic (ie, weight gain, hyperglycaemia and lipid dysregulation) or
      cardiovascular adverse effects. Available safety data from elderly patients
      appear to be promising. Due to negligible hepatic biotransformation, paliperidone
      ER is unlikely to be involved in clinically significant metabolic drug-drug
      interactions. Additional active comparator trials evaluating efficacy,
      tolerability and cost-effectiveness are required to better define the role of
      paliperidone ER in the treatment of schizophrenia in relation to other currently
      available second-generation antipsychotics, particularly risperidone. 

PMID- 23861637
TI  - Safety and efficacy of fingolimod in treatment-naive multiple sclerosis patients.
AB  - Fingolimod was recently approved for use in the United States after two phase III
      trials confirmed its effectiveness in reducing disease activity in relapsing
      remitting multiple sclerosis. These positive results, coupled with the important
      fact that this is the first oral disease-modifying therapy, has lead to
      considerable enthusiasm amongst physicians and patients. However, fingolimod is
      associated with rare but serious adverse events. In addition, unlike conventional
      disease-modifying therapies, cardiopulmonary, ophthalmological and dermatological
      safety monitoring unfamiliar to both neurologists and patients is required before
      and during treatment. This paper will discuss these issues from the perspective
      of using fingolimod as a first-line disease-modifying therapy in treatment-naive
      relapsing-remitting multiple sclerosis patients. 

PMID- 23861638
TI  - Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical
      applications.
AB  - Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on
      MT1 and MT2 melatonin receptors. Ramelteon is the first melatonin receptor
      agonist approved by the Food and Drug Administration (FDA) for the treatment of
      insomnia characterized by sleep onset difficulties. Ramelteon is both a
      chronobiotic and a hypnotic that has been shown to promote sleep initiation and
      maintenance in various preclinical and in clinical trials. The efficacy and
      safety of ramelteon in patients with chronic insomnia was initially confirmed in
      short-term placebo-controlled trials. These showed little evidence of next-day
      residual effects, withdrawal symptoms or rebound insomnia. Other studies
      indicated that ramelteon lacked abuse potential and had a minimal risk of
      producing dependence or adverse effects on cognitive or psychomotor performance.
      A 6-month placebo-controlled international study and a 1-year open-label study in
      the USA demonstrated that ramelteon was effective and well tolerated. Other
      potential off-label uses of ramelteon include circadian rhythm sleep disorders
      such as shift-work and jet lag. At the present time the drug should be cautiously
      prescribed for short-term treatment only. 

PMID- 23861639
TI  - Alzheimers disease: review of emerging treatment role for intravenous
      immunoglobulins.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder. Currently
      available therapies are symptomatic but do not alter underlying disease
      progression. Immunotherapeutic approaches such as anti Abeta peptide active
      vaccination trials have had limited success to date. Intravenous immunoblobulin
      (IVIg) is widely used in immune-mediated neurological disorders such myasthenia
      gravis and Guillain-Barre syndrome. These preparations have been obtained from
      the pooled plasma of healthy human donors and contain natural anti-amyloid
      antibodies and are well tolerated. A small pilot study of passive immunotherapy
      using IVIg has suggested cognitive improvement. A multicenter phase III trial is
      ongoing and will determine whether or not this treatment can ameliorate cognitive
      deficits in mild-to-moderate AD. Here, we briefly review the pathogenic role of
      amyloid and tau in AD, as well as immunotherapeutic efforts to date. We also
      summarize what is known about naturally occurring anti-Abeta and tau antibodies
      in IVIg with a view toward explaining potential mechanisms underlying their
      therapeutic effects. 

PMID- 23861640
TI  - Sertindole in the management of schizophrenia.
AB  - Nowadays, new schizophrenia treatments are more ambitious than ever, aiming not
      only to improve psychotic symptoms, but also quality of life and social
      reinsertion. Our objective is to briefly but critically review the diagnosis of
      schizophrenia, the atypical antipsychotics sertindole's pharmacology, safety and
      status, and mainly evaluate the effects of sertindole compared with other second
      generation antipsychotics for people with schizophrenia and schizophrenia-like
      psychosis. In vitro studies showed that sertindole exerts a potent antagonism at
      serotonin 5-HT2A, 5-HT2C, dopamine D2, and alphal adrenergic receptors.
      Sertindole offers an alternative treatment option for refractory patients given
      its good EPS profile, favorable metabolic profile, and comparable efficacy to
      risperidone. Due to cardiovascular safety concerns, sertindole is available as a
      second-line choice for patients intolerant to other antipsychotic agents. Further
      clinical studies, mainly comparisons with other second-generation antipsychotic
      agents, are needed to define the role of sertindole in the treatment of
      schizophrenia. 

PMID- 23861641
TI  - Dalfampridine: review of its efficacy in improving gait in patients with multiple
      sclerosis.
AB  - Multiple sclerosis (MS) is a progressive immune-mediated neurodegenerative
      disease of human central nervous system (CNS), which causes irreversible
      disability in young adults. The cause and cure for MS remain unknown.
      Pathophysiology of MS includes two arms: inflammatory demyelination and
      neurodegeneration. The inflammatory demyelination of MS which is mainly promoted
      by a massive activation of the immune system against putative CNS antigen(s)
      leads to loss of oligodendrocyte/myelin complex which slows down or halts impulse
      conduction in denuded axons. Practically, loss of myelin significantly reduces
      signal conduction along the demyelinated axons through alterations in the
      distribution of axonal ion channels. Dalfampridine (4-aminopyridine or 4-AP) is
      an oral potassium channel blocker, which was recently approved by FDA for
      symptomatic treatment of MS. Dalfampridine, which acts at the central and
      peripheral nervous systems, enhances conduction in demyelinated axons and
      improves walking ability of MS patients. A number of clinical trials have
      evaluated the safety and efficacy of fampridine in MS patients with the degree of
      gait improvement as the main outcome. The objective of this manuscript is to
      provide an overview of the pharmacology, pharmacokinetics, clinical trials, side
      effects and interactions of dalfampridine used in treatment of MS patients. 

PMID- 23861642
TI  - Risperidone long-acting injection: safety and efficacy in elderly patients with
      schizophrenia.
AB  - Antipsychotic medication is considered the cornerstone of the treatment in
      elderly patients with schizophrenia. Long acting risperidone injection was the
      first antipsychotic available for use in this group of patients. Current
      scientific literature revealed that long-acting risperidone is effective in
      treating the positive and negative symptoms of schizophrenia and some
      improvements in cognition and functioning have also been found. In terms of
      efficacy, there is a paucity of randomized trials but the studies suggest that
      long-acting risperidone is efficient in the long-term management of
      schizophrenia, with a safety profile similar to that of oral risperidone. It
      seems that patient acceptance of treatment is greater when patients are switched
      from a traditional oral medication to depot risperidone and some improvements in
      cognition and functioning might be related. Further long-term comparisons with
      other oral and long-acting antipsychotic medications are needed. These studies
      should include cost-effectiveness data. Research into metabolic side effects is
      also needed. 

PMID- 23861644
TI  - Aripiprazole: a review of its use in the treatment of irritability associated
      with autistic disorder patients aged 6-17.
AB  - A systematic review and meta-analysis were performed examining the efficacy of
      aripiprazole for the treatment of irritability associated with autistic disorder
      in children and adolescents. Aripiprazole was found to be more effective in
      reducing irritability compared with placebo at 8 weeks, SMD -0.64 [-0.90 to 
      0.39, P < 0.00001] as determined by the Aberrant Behaviour Checklist irritability
      subscale (ABC-I). Pooled data from two eight week trials show that sedation is
      the most commonly reported adverse event. Statistically significant weight gain
      was also associated with aripiprazole, but there was a decrease in serum
      prolactin. Most adverse effects were deemed to be mild to moderate in severity.
      Four open trials and three case series all show support for aripiprazole in
      reducing the behavioural symptoms of autism. Long-term studies are required to
      determine the efficacy and safety of aripiprazole in autistic disorder in
      children. 

PMID- 23861645
TI  - Topiramate: safety and efficacy of its use in the prevention and treatment of
      migraine.
AB  - Migraine headaches are typically episodic in nature and may affect nearly 10% of
      the population. In addition to treatment, prevention of subsequent episodes or
      progression to a chronic migraine state is an important therapeutic area.
      Topiramate is a centrally acting medication approved for both the prevention of
      seizures and migraine headache. At this time, the exact mechanism of how
      topiramate assists in migraine prevention is unknown. Several large randomized,
      controlled trials have aided in establishing topiramate's role in migraine
      prevention. Despite a favorable pharmacokinetic and adverse effect profile
      established in clinical trials, several additional studies, case reports and
      toxicology reports have demonstrated topiramate as a cause of cognitive and
      behavioural changes. The use of topiramate in migraine prevention can improve a
      patient's quality of life and is a cost-effective option for migraine prevention.

PMID- 23861643
TI  - Evidence-based pharmacotherapy for pediatric obsessive-compulsive disorder and
      chronic tic disorders.
AB  - In recent years, much progress has been made in pharmacotherapy for pediatric
      obsessive-compulsive disorder (OCD) and chronic tic disorders (CTDs). What were
      previously considered relatively intractable conditions now have an array of
      efficacious medicinal (and psychosocial) interventions available at clinicians'
      disposal, including selective serotonin reuptake inhibitors, atypical
      antipsychotics, and alpha-2 agonists. The purpose of this review is to discuss
      the evidence base for pharmacotherapy with pediatric OCD and CTDs with regard to
      efficacy, tolerability, and safety, and to put this evidence in the context of
      clinical management in integrated behavioral healthcare. While there is no single
      panacea for these disorders, there are a variety of medications that provide
      considerable relief for children with these disabling conditions. 

PMID- 23861646
TI  - Pramipexole and its extended release formulation for Parkinson's disease.
AB  - Pramipexole has been a widely used dopamine agonist for the last decade. Recently
      an extended release formulation of pramipexole has been introduced as both
      monotherapy for patients with early Parkinson's disease as well as for patients
      with more advanced disease, as an adjunct to L-DOPA. Along with the enhanced
      patient compliance seen with once a day dosing, there are other potential
      advantages of extended release preparations of dopamine agonists. Patients
      initiated on pramipexole have a lower incidence of developing motor fluctuations
      including dyskinesia than those initiated on L-DOPA. Pramipexole requires a
      prolonged dose titration compared to L-DOPA, and generally does not have the
      efficacy of L-DOPA. The extended release form of pramipexole shows comparable
      mean and peak serum levels with once a day dosing as seen with three times a day
      dosing of the immediate release preparation. The extended release preparation has
      been studied in randomized multicenter clinical trial against both placebo and
      the immediate release preparation in the setting of early Parkinson's disease as
      monotherapy and in more advanced patients with motor fluctuations on L-DOPA. In
      both settings the extended release preparation was superior to placebo and
      comparable to the immediate release form in efficacy with a similar side effect
      profile including nausea, sleepiness, leg edema, dyskinesias, hallucinations and
      impulse control disorders. 

PMID- 23861647
TI  - A review of eslicarbazepine acetate for the adjunctive treatment of partial-onset
      epilepsy.
AB  - Eslicarbazepine acetate (ESL) is a novel antiepileptic drug indicated for the
      treatment of partial-onset seizures. Structurally, it belongs to the
      dibenzazepine family and is closely related to carbamazepine and oxcarbazepine.
      Its main mechanism of action is by blocking the voltage-gated sodium channel. ESL
      is a pro-drug that is rapidly metabolized almost exclusively into S
      licarbazepine, the biologically active drug. It has a favorable pharmacokinetic
      and drug-drug interaction profile. However, it may induce the metabolism of oral
      contraceptives and should be used with caution in females of child-bearing age.
      In the pre-marketing placebo-controlled clinical trials ESL has proven effective
      as adjunctive therapy in adult patients with refractory of partial-onset
      seizures. Best results were observed on a single daily dose between 800 and 1200
      mg. In general, ESL was well tolerated, with most common dose-related side
      effects including dizziness, somnolence, headache, nausea and vomiting.
      Hyponatremia has been observed (0.6%-1.3%), but the incidence appears to be lower
      than with the use of oxcarbazepine. There is very limited information on the use
      of ESL in children or as monotherapy. 

PMID- 23861649
TI  - Safety and efficacy of vigabatrin for the treatment of infantile spasms.
AB  - In 2009, vigabatrin became the first FDA approved medication for the treatment of
      infantile spasms in the United States. There are few well-designed prospective
      studies comparing the drug to placebo or other modalities used in the treatment
      of infantile spasms. The available data have demonstrated that vigabatrin is
      efficacious in the treatment of infantile spasms regardless of underlying
      etiology, but that it is particularly beneficial in patients with a diagnosis of
      tuberous sclerosis. Adrenocorticotropic hormone (ACTH), the only other medication
      with robust efficacy data, has been used as first line therapy for infantile
      spasms associated with other etiologies, and in general controls spasms sooner
      than vigabatrin, though relapse is common with both therapies. Vigabatrin is
      generally well tolerated. However, use has been associated with permanent loss of
      peripheral vision in some patients. In children with tuberous sclerosis,
      vigabatrin should be considered as initial therapy for infantile spasms. It is a
      viable alternative for patients with suboptimal response, contraindications or
      intolerance to ACTH. 

PMID- 23861648
TI  - Current and emerging therapies for the management of bipolar disorders.
AB  - Bipolar disorder is a complex condition to treat because agents that may be
      effective for a specific phase may not be effective for other phases, or may even
      worsen the overall course of the illness. Over the last decade there has been an
      increase in research activity in the treatment of bipolar illness. There are now
      several agents that are well established for the treatment of acute mania
      (lithium, divalproex, carbamazepine, nearly all antipsychotics), acute bipolar
      depression (lamotrigine, quetiapine, olanzapine/fluoxetine combination), and
      relapse prevention (lithium, lamotrigine, divalproex, most second generation
      antipsychotics). There are also novel treatments that are being studied for all
      three phases. These include eslicarbazepine, cariprazine, MEM-1003, memantine,
      tamoxifen and pentazocine for acute mania; pramipexole, modafinil, armodafinil,
      divalproex, lurasidone, agomelatine, cariprazine, lisedexamfetamine, riluzole, RG
      2417, bifeprunox, ropinirole, GSK1014802, and magnetic stimulation for bipolar
      depression; and asenapine, lurasidone, and cariprazine for relapse prevention.
      Additionally, there are accumulating data that antidepressants, particularly
      serotoninergic ones, are not particularly effective in acute bipolar depression
      and may worsen the course of the illness. 

PMID- 23861650
TI  - Atomoxetine in children and adolescents with attention-deficit/hyperactivity
      disorder. Systematic review of review papers 2009-2011. An update for clinicians.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a common disorder and a
      plethora of new data has been published from clinical trials and national
      epidemiological databases in the last three years. In the United Kingdom
      Atomoxetine is currently the only licensed non-stimulant medication. As part of a
      systematic review of atomoxetine data Jan 2009-June 2011 formal searches found
      750 citations. From these 13 met criteria for either review or systematic review
      papers and contained clinical data synthesis on atomoxetine. No individual review
      paper alone would be sufficient for clinicians to be updated at that time on all
      clinical aspects of atomoxetine data. The crucial data relating to clinical
      parity of atomoxetine and methylphenidate in trials and meta-analysis where
      relevant confounding biases are removed are not often discussed. Systematic
      review of complex data is critical for ADHD clinicians and will need regular
      updating due to the large volume of new data. 

PMID- 23861651
TI  - Monitor, a vibrotactile aid for environmental perception: a field evaluation by
      four people with severe hearing and vision impairment.
AB  - Monitor is a portable vibrotactile aid to improve the ability of people with
      severe hearing impairment or deafblindness to detect, identify, and recognize the
      direction of sound-producing events. It transforms and adapts sounds to the
      frequency sensitivity range of the skin. The aid was evaluated in the field. Four
      females (44-54 years) with Usher Syndrome I (three with tunnel vision and one
      with only light perception) tested the aid at home and in traffic in three
      different field studies: without Monitor, with Monitor with an omnidirectional
      microphone, and with Monitor with a directional microphone. The tests were video
      documented, and the two field studies with Monitor were initiated after five
      weeks of training. The detection scores with omnidirectional and directional
      microphones were 100% for three participants and above 57% for one, both in their
      home and traffic environments. In the home environment the identification scores
      with the omnidirectional microphone were 70%-97% and 58%-95% with the directional
      microphone. The corresponding values in traffic were 29%-100% and 65%-100%,
      respectively. Their direction perception was improved to some extent by both
      microphones. Monitor improved the ability of people with deafblindness to detect,
      identify, and recognize the direction of events producing sounds. 

PMID- 23861652
TI  - Multilevel tunnelling systems and fractal clustering in the low-temperature mixed
      alkali-silicate glasses.
AB  - The thermal and dielectric anomalies of window-type glasses at low temperatures
      (T < 1 K) are rather successfully explained by the two-level systems (2LS)
      standard tunneling model (STM). However, the magnetic effects discovered in the
      multisilicate glasses in recent times, magnetic effects in the organic glasses,
      and also some older data from mixed (SiO2)(1-x) (K2O)(x) and (SiO2)(1-x)
      (Na2O)(x) glasses indicate the need for a suitable extension of the 2LS-STM. We
      show that--not only for the magnetic effects, but also for the mixed glasses in
      the absence of a field--the right extension of the 2LS-STM is provided by the
      (anomalous) multilevel tunnelling systems (ATS) proposed by one of us for
      multicomponent amorphous solids. Though a secondary type of TS, different from
      the standard 2LS, was invoked long ago already, we clarify their physical origin
      and mathematical description and show that their contribution considerably
      improves the agreement with the experimental data. In spite of dealing with low
      temperature properties, our work impinges on the structure and statistical
      physics of glasses at all temperatures.

PMID- 23861653
TI  - Effluents of shrimp farms and its influence on the coastal ecosystems of Bahia de
      Kino, Mexico.
AB  - The impact on coastal ecosystems of suspended solids, organic matter, and
      bacteria in shrimp farm effluents is presented. Sites around Bahia de Kino were
      selected for comparative evaluation. Effluent entering Bahia Kino (1) enters
      Laguna La Cruz (2). A control site (3) was outside the influence of effluents.
      Water quality samples were collected every two weeks during the shrimp culture
      period. Our data show that the material load in shrimp farm effluents changes
      biogeochemical processes and aquatic health of the coastal ecosystem.
      Specifically, the suspended solids, particulate organic matter, chlorophyll a,
      viable heterotrophic bacteria, and Vibrio-like bacteria in the bay and lagoon
      were two- to three-fold higher than the control site. This can be mitigated by
      improvements in the management of aquaculture systems. 

PMID- 23861654
TI  - Petrography and physicomechanical properties of rocks from the Ambela granitic
      complex, NW Pakistan.
AB  - Petrography and physicomechanical properties of alkali granites, alkali quartz
      syenite, and nepheline syenite from Ambela, NW Pakistan, have been investigated.
      Whereas the alkali quartz syenite and most of the alkali granites are
      megaporphyritic, the nepheline syenite and some of the alkali granites are
      microporphyritic. Their phenocryst shape and size and abundance of groundmass are
      also different. The values of unconfined compressive strength (UCS) are the
      lowest and highest for megaporphyritic alkali granite and alkali quartz syenite,
      respectively. However, all the four rock types are moderately strong.
      Correspondingly, their specific gravity and water absorption values are within
      the permissible range for use as construction material. The UCS for the alkali
      quartz syenite is the highest, most probably because (i) it has roughly equal
      amounts of phenocryst and groundmass, (ii) it displays maximum size contrast
      between phenocryst and groundmass, (iii) its phenocrysts are highly irregular,
      and (iv) it contains substantial amounts of quartz. 

PMID- 23861655
TI  - An approach to self-assembling swarm robots using multitree genetic programming.
AB  - In recent days, self-assembling swarm robots have been studied by a number of
      researchers due to their advantages such as high efficiency, stability, and
      scalability. However, there are still critical issues in applying them to
      practical problems in the real world. The main objective of this study is to
      develop a novel self-assembling swarm robot algorithm that overcomes the
      limitations of existing approaches. To this end, multitree genetic programming is
      newly designed to efficiently discover a set of patterns necessary to carry out
      the mission of the self-assembling swarm robots. The obtained patterns are then
      incorporated into their corresponding robot modules. The computational
      experiments prove the effectiveness of the proposed approach. 

PMID- 23861656
TI  - Targeting the vasculature of colorectal carcinoma with a fused protein of (RGD)3
      tTF.
AB  - PURPOSE: Truncated tissue factor (tTF) fusion protein targeting tumor vasculature
      can induce tumor vascular thrombosis and necrosis. Here, we generated (RGD)3-tTF
      in which three arginine-glycine-aspartic (RGD) targeting integrin alpha(v)beta3
      and tTF induce blood coagulation in tumor vessels. METHODS: The bioactivities of
      (RGD)3-tTF including coagulation activity, FX activation, and binding with
      integrin alpha(v)beta3 were performed. The fluorescent labeled (RGD)3-tTF was
      intravenously injected into tumor-bearing mice and traced in vivo. The tumor
      growth, volume, blood vessel thrombosis, tumor necrosis, and survival time of
      mice treated with (RGD)3-tTF were evaluated. RESULTS: The clotting time and FX
      activation of (RGD)3-tTF were similar to that of TF (P > 0.05) but different with
      that of RGD (P < 0.05). (RGD)3-tTF presented a higher binding with alpha(v)beta3
      than that of RGD and TF at the concentration of 0.2 MUmol/L (P < 0.05). (RGD)3
      tTF could specifically assemble in tumor and be effective in reducing tumor
      growth by selectively inducing tumor blood vessels thrombosis and tumor necrosis
      which were absent in mice treated with RGD or TF. The survival time of mice
      treated with (RGD)3-tTF was higher than that of mice treated with TF or RGD (P <
      0.05). CONCLUSION: (RGD)3-tTF may be a promising strategy for the treatment of
      colorectal cancer.

PMID- 23861657
TI  - Investigation of the effects of length to depth ratio on open supersonic cavities
      using CFD and proper orthogonal decomposition.
AB  - Simulations of supersonic turbulent flow over an open rectangular cavity are
      performed to observe the effects of length to depth ratio (L/D) of the cavity on
      the flow structure. Two-dimensional compressible time-dependent Reynolds-averaged
      Navier-Stokes equations with k-omega turbulence model are solved. A reduced order
      modeling approach, Proper Orthogonal Decomposition (POD) method, is used to
      further analyze the flow. Results are obtained for cavities with several L/D
      ratios at a Mach number of 1.5. Mostly, sound pressure levels (SPL) are used for
      comparison. After a reduced order modeling approach, the number of modes
      necessary to represent the systems is observed for each case. The necessary
      minimum number of modes to define the system increases as the flow becomes more
      complex with the increase in the L/D ratio. This study provides a basis for the
      control of flow over supersonic open cavities by providing a reduced order model
      for flow control, and it also gives an insight to cavity flow physics by
      comparing several simulation results with different length to depth ratios. 

PMID- 23861658
TI  - Research on hysteresis of piezoceramic actuator based on the Duhem model.
AB  - To improve the modeling accuracy of piezoceramic actuator in the precision
      positioning system, the Duhem hysteretic model of the piezoceramic actuator was
      proposed. The paper used the polynomial function to approach the piecewise
      continuous function and f(v) and g(v) in the Duhem model, adopted recursive least
      squares algorithm and gradient correction algorithm to identify parameter alpha ,
      polynomial coefficients of f and g in the Duhem model, and established the
      nonlinear parametric model of the piezoceramic actuator. Contrasting the
      simulation results of recursive least squares algorithm and gradient correction
      algorithm, the modeling accuracy is 0.24% when adopting the recursive least
      squares algorithm, and the modeling accuracy is 0.11% when adopting the gradient
      correction method. The result showed that the gradient correction algorithm could
      meet the modeling accuracy better, and the structure of the algorithm is simple,
      adaptable, and easy to implement. 

PMID- 23861659
TI  - Effect of Glu-B3 allelic variation on sodium dodecyl sulfate sedimentation volume
      in common wheat (Triticum aestivum L.).
AB  - Sodium dodecyl sulfate (SDS) sedimentation volume has long been used to
      characterize wheat flours and meals with the aim of predicting processing and end
      product qualities. In order to survey the influence of low-molecular-weight
      glutenin subunits (LMW-GSs) at Glu-B3 locus on wheat SDS sedimentation volume, a
      total of 283 wheat (Triticum aestivum L.) varieties including landraces and
      improved and introduced cultivars were analyzed using 10 allele-specific PCR
      markers at the Glu-B3 locus. The highest allele frequency observed in the tested
      varieties was Glu-B3i with 21.9% in all varieties, 21.1% in landraces, 25.5% in
      improved cultivars, and 12% in introduced cultivars. Glu-B3 locus represented
      8.6% of the variance in wheat SDS sedimentation volume, and Glu-B3b, Glu-B3g, and
      Glu-B3h significantly heightened the SDS sedimentation volume, but Glu-B3a, Glu
      B3c, and Glu-B3j significantly lowered the SDS sedimentation volume. For the
      bread-making quality, the most desirable alleles Glu-B3b and Glu-B3g become more
      and more popular and the least desirable alleles Glu-B3a and Glu-B3c got less and
      less in modern improved cultivars, suggesting that wheat grain quality in China
      has been significantly improved through breeding effort. 

PMID- 23861660
TI  - Interaction of motility, directional sensing, and polarity modules recreates the
      behaviors of chemotaxing cells.
AB  - Chemotaxis involves the coordinated action of separable but interrelated
      processes: motility, gradient sensing, and polarization. We have hypothesized
      that these are mediated by separate modules that account for these processes
      individually and that, when combined, recreate most of the behaviors of
      chemotactic cells. Here, we describe a mathematical model where the modules are
      implemented in terms of reaction-diffusion equations. Migration and the
      accompanying changes in cellular morphology are demonstrated in simulations using
      a mechanical model of the cell cortex implemented in the level set framework. The
      central module is an excitable network that accounts for random migration. The
      response to combinations of uniform stimuli and gradients is mediated by a local
      excitation, global inhibition module that biases the direction in which
      excitability is directed. A polarization module linked to the excitable network
      through the cytoskeleton allows unstimulated cells to move persistently and, for
      cells in gradients, to gradually acquire distinct sensitivity between front and
      back. Finally, by varying the strengths of various feedback loops in the model we
      obtain cellular behaviors that mirror those of genetically altered cell lines.

PMID- 23861661
TI  - Predicting network activity from high throughput metabolomics.
AB  - The functional interpretation of high throughput metabolomics by mass
      spectrometry is hindered by the identification of metabolites, a tedious and
      challenging task. We present a set of computational algorithms which, by
      leveraging the collective power of metabolic pathways and networks, predict
      functional activity directly from spectral feature tables without a priori
      identification of metabolites. The algorithms were experimentally validated on
      the activation of innate immune cells. 

PMID- 23861662
TI  - Pathway-based screening strategy for multitarget inhibitors of diverse proteins
      in metabolic pathways.
AB  - Many virtual screening methods have been developed for identifying single-target
      inhibitors based on the strategy of "one-disease, one-target, one-drug". The hit
      rates of these methods are often low because they cannot capture the features
      that play key roles in the biological functions of the target protein.
      Furthermore, single-target inhibitors are often susceptible to drug resistance
      and are ineffective for complex diseases such as cancers. Therefore, a new
      strategy is required for enriching the hit rate and identifying multitarget
      inhibitors. To address these issues, we propose the pathway-based screening
      strategy (called PathSiMMap) to derive binding mechanisms for increasing the hit
      rate and discovering multitarget inhibitors using site-moiety maps. This strategy
      simultaneously screens multiple target proteins in the same pathway; these
      proteins bind intermediates with common substructures. These proteins possess
      similar conserved binding environments (pathway anchors) when the product of one
      protein is the substrate of the next protein in the pathway despite their low
      sequence identity and structure similarity. We successfully discovered two
      multitarget inhibitors with IC50 of <10 uM for shikimate dehydrogenase and
      shikimate kinase in the shikimate pathway of Helicobacter pylori. Furthermore, we
      found two selective inhibitors (IC50 of <10 uM) for shikimate dehydrogenase using
      the specific anchors derived by our method. Our experimental results reveal that
      this strategy can enhance the hit rates and the pathway anchors are highly
      conserved and important for biological functions. We believe that our strategy
      provides a great value for elucidating protein binding mechanisms and discovering
      multitarget inhibitors. 

PMID- 23861663
TI  - Engineering a more thermostable blue light photo receptor Bacillus subtilis YtvA
      LOV domain by a computer aided rational design method.
AB  - The ability to design thermostable proteins offers enormous potential for the
      development of novel protein bioreagents. In this work, a combined computational
      and experimental method was developed to increase the T m of the flavin
      mononucleotide based fluorescent protein Bacillus Subtilis YtvA LOV domain by 31
      Celsius, thus extending its applicability in thermophilic systems. Briefly, the
      method includes five steps, the single mutant computer screening to identify
      thermostable mutant candidates, the experimental evaluation to confirm the
      positive selections, the computational redesign around the thermostable mutation
      regions, the experimental reevaluation and finally the multiple mutations
      combination. The adopted method is simple and effective, can be applied to other
      important proteins where other methods have difficulties, and therefore provides
      a new tool to improve protein thermostability. 

PMID- 23861664
TI  - Predictors of hepatitis B cure using gene therapy to deliver DNA cleavage
      enzymes: a mathematical modeling approach.
AB  - Most chronic viral infections are managed with small molecule therapies that
      inhibit replication but are not curative because non-replicating viral forms can
      persist despite decades of suppressive treatment. There are therefore numerous
      strategies in development to eradicate all non-replicating viruses from the body.
      We are currently engineering DNA cleavage enzymes that specifically target
      hepatitis B virus covalently closed circular DNA (HBV cccDNA), the episomal form
      of the virus that persists despite potent antiviral therapies. DNA cleavage
      enzymes, including homing endonucleases or meganucleases, zinc-finger nucleases
      (ZFNs), TAL effector nucleases (TALENs), and CRISPR-associated system 9 (Cas9)
      proteins, can disrupt specific regions of viral DNA. Because DNA repair is error
      prone, the virus can be neutralized after repeated cleavage events when a target
      sequence becomes mutated. DNA cleavage enzymes will be delivered as genes within
      viral vectors that enter hepatocytes. Here we develop mathematical models that
      describe the delivery and intracellular activity of DNA cleavage enzymes. Model
      simulations predict that high vector to target cell ratio, limited removal of
      delivery vectors by humoral immunity, and avid binding between enzyme and its DNA
      target will promote the highest level of cccDNA disruption. Development of de
      novo resistance to cleavage enzymes may occur if DNA cleavage and error prone
      repair does not render the viral episome replication incompetent: our model
      predicts that concurrent delivery of multiple enzymes which target different
      vital cccDNA regions, or sequential delivery of different enzymes, are both
      potentially useful strategies for avoiding multi-enzyme resistance. The
      underlying dynamics of cccDNA persistence are unlikely to impact the probability
      of cure provided that antiviral therapy is given concurrently during eradication
      trials. We conclude by describing experiments that can be used to validate the
      model, which will in turn provide vital information for dose selection for
      potential curative trials in animals and ultimately humans. 

PMID- 23861665
TI  - Budding yeast greatwall and endosulfines control activity and spatial regulation
      of PP2A(Cdc55) for timely mitotic progression.
AB  - Entry into mitosis is triggered by cyclinB/Cdk1, whose activity is abruptly
      raised by a positive feedback loop. The Greatwall kinase phosphorylates proteins
      of the endosulfine family and allows them to bind and inhibit the main Cdk1
      counteracting PP2A-B55 phosphatase, thereby promoting mitotic entry. In contrast
      to most eukaryotic systems, Cdc14 is the main Cdk1-antagonizing phosphatase in
      budding yeast, while the PP2A(Cdc55) phosphatase promotes, instead of preventing,
      mitotic entry by participating to the positive feedback loop of Cdk1 activation.
      Here we show that budding yeast endosulfines (Igo1 and Igo2) bind to PP2A(Cdc55)
      in a cell cycle-regulated manner upon Greatwall (Rim15)-dependent
      phosphorylation. Phosphorylated Igo1 inhibits PP2A(Cdc55) activity in vitro and
      induces mitotic entry in Xenopus egg extracts, indicating that it bears a
      conserved PP2A-binding and -inhibitory activity. Surprisingly, deletion of IGO1
      and IGO2 in yeast cells leads to a decrease in PP2A phosphatase activity,
      suggesting that endosulfines act also as positive regulators of PP2A in yeast.
      Consistently, RIM15 and IGO1/2 promote, like PP2A(Cdc55), timely entry into
      mitosis under temperature-stress, owing to the accumulation of Tyr-phosphorylated
      Cdk1. In addition, they contribute to the nuclear export of PP2A(Cdc55), which
      has recently been proposed to promote mitotic entry. Altogether, our data
      indicate that Igo proteins participate in the positive feedback loop for Cdk1
      activation. We conclude that Greatwall, endosulfines, and PP2A are part of a
      regulatory module that has been conserved during evolution irrespective of PP2A
      function in the control of mitosis. However, this conserved module is adapted to
      account for differences in the regulation of mitotic entry in different
      organisms. 

PMID- 23861666
TI  - Mapping of PARK2 and PACRG overlapping regulatory region reveals LD structure and
      functional variants in association with leprosy in unrelated indian population
      groups.
AB  - Leprosy is a chronic infectious disease caused by Mycobacterium Leprae, where the
      host genetic background plays an important role toward the disease pathogenesis.
      Various studies have identified a number of human genes in association with
      leprosy or its clinical forms. However, non-replication of results has hinted at
      the heterogeneity among associations between different population groups, which
      could be due to differently evolved LD structures and differential frequencies of
      SNPs within the studied regions of the genome. A need for systematic and
      saturated mapping of the associated regions with the disease is warranted to
      unravel the observed heterogeneity in different populations. Mapping of the PARK2
      and PACRG gene regulatory region with 96 SNPs, with a resolution of 1 SNP per 1
      Kb for PARK2 gene regulatory region in a North Indian population, showed an
      involvement of 11 SNPs in determining the susceptibility towards leprosy. The
      association was replicated in a geographically distinct and unrelated population
      from Orissa in eastern India. In vitro reporter assays revealed that the two
      significantly associated SNPs, located 63.8 kb upstream of PARK2 gene and
      represented in a single BIN of 8 SNPs, influenced the gene expression. A
      comparison of BINs between Indian and Vietnamese populations revealed differences
      in the BIN structures, explaining the heterogeneity and also the reason for non
      replication of the associated genomic region in different populations. 

PMID- 23861667
TI  - Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell
      functions through trans-regulation of gene networks.
AB  - The chromosome 9p21 (Chr9p21) locus of coronary artery disease has been
      identified in the first surge of genome-wide association and is the strongest
      genetic factor of atherosclerosis known today. Chr9p21 encodes the long non
      coding RNA (ncRNA) antisense non-coding RNA in the INK4 locus (ANRIL). ANRIL
      expression is associated with the Chr9p21 genotype and correlated with
      atherosclerosis severity. Here, we report on the molecular mechanisms through
      which ANRIL regulates target-genes in trans, leading to increased cell
      proliferation, increased cell adhesion and decreased apoptosis, which are all
      essential mechanisms of atherogenesis. Importantly, trans-regulation was
      dependent on Alu motifs, which marked the promoters of ANRIL target genes and
      were mirrored in ANRIL RNA transcripts. ANRIL bound Polycomb group proteins that
      were highly enriched in the proximity of Alu motifs across the genome and were
      recruited to promoters of target genes upon ANRIL over-expression. The functional
      relevance of Alu motifs in ANRIL was confirmed by deletion and mutagenesis,
      reversing trans-regulation and atherogenic cell functions. ANRIL-regulated
      networks were confirmed in 2280 individuals with and without coronary artery
      disease and functionally validated in primary cells from patients carrying the
      Chr9p21 risk allele. Our study provides a molecular mechanism for pro-atherogenic
      effects of ANRIL at Chr9p21 and suggests a novel role for Alu elements in
      epigenetic gene regulation by long ncRNAs. 

PMID- 23861668
TI  - Effective blocking of the white enhancer requires cooperation between two main
      mechanisms suggested for the insulator function.
AB  - Chromatin insulators block the action of transcriptional enhancers when
      interposed between an enhancer and a promoter. In this study, we examined the
      role of chromatin loops formed by two unrelated insulators, gypsy and Fab-7, in
      their enhancer-blocking activity. To test for this activity, we selected the
      white reporter gene that is activated by the eye-specific enhancer. The results
      showed that one copy of the gypsy or Fab-7 insulator failed to block the eye
      enhancer in most of genomic sites, whereas a chromatin loop formed by two gypsy
      insulators flanking either the eye enhancer or the reporter completely blocked
      white stimulation by the enhancer. However, strong enhancer blocking was achieved
      due not only to chromatin loop formation but also to the direct interaction of
      the gypsy insulator with the eye enhancer, which was confirmed by the 3C assay.
      In particular, it was observed that Mod(mdg4)-67.2, a component of the gypsy
      insulator, interacted with the Zeste protein, which is critical for the eye
      enhancer-white promoter communication. These results suggest that efficient
      enhancer blocking depends on the combination of two factors: chromatin loop
      formation by paired insulators, which generates physical constraints for enhancer
      promoter communication, and the direct interaction of proteins recruited to an
      insulator and to the enhancer-promoter pair. 

PMID- 23861669
TI  - Monopolin subunit Csm1 associates with MIND complex to establish monopolar
      attachment of sister kinetochores at meiosis I.
AB  - Sexually reproducing organisms halve their cellular ploidy during gametogenesis
      by undergoing a specialized form of cell division known as meiosis. During
      meiosis, a single round of DNA replication is followed by two rounds of nuclear
      divisions (referred to as meiosis I and II). While sister kinetochores bind to
      microtubules emanating from opposite spindle poles during mitosis, they bind to
      microtubules originating from the same spindle pole during meiosis I. This
      phenomenon is referred to as mono-orientation and is essential for setting up the
      reductional mode of chromosome segregation during meiosis I. In budding yeast,
      mono-orientation depends on a four component protein complex referred to as
      monopolin which consists of two nucleolar proteins Csm1 and Lrs4, meiosis
      specific protein Mam1 of unknown function and casein kinase Hrr25. Monopolin
      complex binds to kinetochores during meiosis I and prevents bipolar attachments.
      Although monopolin associates with kinetochores during meiosis I, its binding
      site(s) on the kinetochore is not known and its mechanism of action has not been
      established. By carrying out an imaging-based screen we have found that the MIND
      complex, a component of the central kinetochore, is required for monopolin
      association with kinetochores during meiosis. Furthermore, we demonstrate that
      interaction of monopolin subunit Csm1 with the N-terminal domain of MIND complex
      subunit Dsn1, is essential for both the association of monopolin with
      kinetochores and for monopolar attachment of sister kinetochores during meiosis
      I. As such this provides the first functional evidence for a monopolin-binding
      site at the kinetochore. 

PMID- 23861670
TI  - Histone methyltransferase DOT1L drives recovery of gene expression after a
      genotoxic attack.
AB  - UV-induced DNA damage causes repression of RNA synthesis. Following the removal
      of DNA lesions, transcription recovery operates through a process that is not
      understood yet. Here we show that knocking-out of the histone methyltransferase
      DOT1L in mouse embryonic fibroblasts (MEF(DOT1L)) leads to a UV hypersensitivity
      coupled to a deficient recovery of transcription initiation after UV irradiation.
      However, DOT1L is not implicated in the removal of the UV-induced DNA damage by
      the nucleotide excision repair pathway. Using FRAP and ChIP experiments we
      established that DOT1L promotes the formation of the pre-initiation complex on
      the promoters of UV-repressed genes and the appearance of transcriptionally
      active chromatin marks. Treatment with Trichostatin A, relaxing chromatin,
      recovers both transcription initiation and UV-survival. Our data suggest that
      DOT1L secures an open chromatin structure in order to reactivate RNA Pol II
      transcription initiation after a genotoxic attack. 

PMID- 23861671
TI  - Accuracy of the Charlson index comorbidities derived from a hospital electronic
      database in a teaching hospital in Saudi Arabia.
AB  - Hospital management and researchers are increasingly using electronic databases
      to study utilization, effectiveness, and outcomes of healthcare provision.
      Although several studies have examined the accuracy of electronic databases
      developed for general administrative purposes, few studies have examined
      electronic databases created to document the care provided by individual
      hospitals. In this study, we assessed the accuracy of an electronic database in a
      major teaching hospital in Eastern Province, Saudi Arabia, in documenting the 17
      comorbidities constituting the Charlson index as recorded in paper charts by care
      providers. Using the hospital electronic database, the researchers randomly
      selected the data for 1,019 patients admitted to the hospital and compared the
      data for accuracy with the corresponding paper charts. Compared with the paper
      charts, the hospital electronic database did not differ significantly in
      prevalence for 9 conditions but differed from the paper charts for 8 conditions.
      The kappa (K) values of agreement ranged from a high of 0.91 to a low of 0.09. Of
      the 17 comorbidities, the electronic database had substantial or excellent
      agreement for 10 comorbidities relative to paper chart data, and only one showed
      poor agreement. Sensitivity ranged from a high of 100.0 percent to a low of 6.0
      percent. Specificity for all comorbidities was greater than 93 percent. The
      results suggest that the hospital electronic database reasonably agrees with
      patient chart data and can have a role in healthcare planning and research. The
      analysis conducted in this study could be performed in individual institutions to
      assess the accuracy of an electronic database before deciding on its utility in
      planning or research. 

PMID- 23861672
TI  - Flexible approaches for teaching computational genomics in a health information
      management program.
AB  - The astonishing improvement of high-throughput biotechnologies in recent years
      makes it possible to access a huge amount of genomic data. The association
      between genomic data and genetic disease has already been and will continue to be
      applied to personalized healthcare. Health information management (HIM)
      professionals are the ones who will handle personal genetic information and
      provide solid evidence to support physicians' diagnoses and personalized
      treatment strategies, and therefore they will need to have the knowledge and
      skills to process genomic data. In this paper, we describe flexible approaches
      for teaching a computational genomics course in the HIM program at the University
      of Pittsburgh. HIM programs at other universities may choose an appropriate
      approach to fit into their own curriculum. 

PMID- 23861674
TI  - From novice to expert: problem solving in ICD-10-PCS procedural coding.
AB  - The benefits of converting to ICD-10-CM/PCS have been well documented in recent
      years. One of the greatest challenges in the conversion, however, is how to train
      the workforce in the code sets. The International Classification of Diseases,
      Tenth Revision, Procedure Coding System (ICD-10-PCS) has been described as a
      language requiring higher-level reasoning skills because of the system's
      increased granularity. Training and problem-solving strategies required for
      correct procedural coding are unclear. The objective of this article is to
      propose that the acquisition of rule-based logic will need to be augmented with
      self-evaluative and critical thinking. Awareness of how this process works is
      helpful for established coders as well as for a new generation of coders who will
      master the complexities of the system. 

PMID- 23861673
TI  - Implementing an online reporting system in the anatomical pathology department of
      a tertiary care teaching hospital in India: a case study.
AB  - This article presents a case study in designing, developing, and implementing a
      web-enabled reporting application for the anatomical pathology (histopathology)
      department of a tertiary care teaching hospital in India. The article describes
      workflows, requirements assessment, and implementation methods that the
      investigators adopted for deploying the solution. The primary focus of the study
      was to demonstrate the requirements assessment performed, the strategies adopted,
      and the challenges encountered during the development and implementation. The
      study demonstrates a successful deployment as well as successful adoption of
      healthcare information technology by the end users. Factors that played a crucial
      role in adoption included the combination of people, processes, and technology.
      The lessons learned from this study would help application developers design
      efficient systems that suit the requirements of the end users while keeping in
      mind the ever-changing need for workflows and scalability in a developing
      country. 

PMID- 23861675
TI  - Use of structured and unstructured data to identify contraceptive use in women
      veterans.
AB  - Contraceptive use among women Veterans may not be adequately captured using
      administrative and pharmacy codes. Clinical progress notes may provide a useful
      alternative. The objectives of this study were to validate the use of
      administrative and pharmacy codes to identify contraceptive use in Veterans
      Health Administration data, and to determine the feasibility and validity of
      identifying contraceptive use in clinical progress notes. The study included
      women Veterans who participated in the Women Veterans Cohort Study, enrolled in
      the Veterans Affairs Connecticut Health Care System, completed a baseline survey,
      and had clinical progress notes from one year prior to survey completion.
      Contraceptive ICD-9-CM codes, V-codes, CPT codes, and pharmacy codes were
      identified. Progress notes were annotated to identify contraceptive use. Self
      reported contraceptive use was identified from a baseline survey of health habits
      and healthcare practices and utilization. Sensitivity, specificity, and positive
      predictive value were calculated comparing administrative and pharmacy
      contraceptive codes and progress note-based contraceptive information to self
      report survey data. Results showed that administrative and pharmacy codes were
      specific but not sensitive for identifying contraceptive use. For example, oral
      contraceptive pill codes were highly specific (1.00) but not sensitive (0.41).
      Data from clinical progress notes demonstrated greater sensitivity and comparable
      specificity. For example, for oral contraceptive pills, progress notes were both
      specific (0.85) and sensitive (0.73). Results suggest that the best approach for
      identifying contraceptive use, through either administrative codes or progress
      notes, depends on the research question. 

PMID- 23861676
TI  - Telepsychiatry in the 21(st) century: transforming healthcare with technology.
AB  - This article describes the benefits and constraints of telemedicine, focusing
      primarily on the field of psychiatry in the United States with the current system
      of healthcare. Telepsychiatry is believed to provide better access and higher
      quality care to patients who need psychiatric care and cost savings to providers
      of such care. Telemedicine has been successfully integrated into psychiatric
      facilities reaching rural areas, prisons, and urban facilities. It has increased
      the volume of patients that physicians can reach and diagnose, as well as
      allowing them to treat patients with limitations in mobility. While
      telepsychiatry has been shown to be beneficial, this technology does have some
      limitations. Concerns about reimbursement, licensure, privacy, security, patient
      safety, and interoperability have been identified and present current challenges
      that providers using telepsychiatry must overcome in order to provide the most
      effective patient care. As more insurance companies start to reimburse for
      telepsychiatry treatments at the same rate as for face-to-face visits, this
      evolving medical field has the potential to grow exponentially. 

PMID- 23861677
TI  - ICD-10-CM/PCS: transferring knowledge from ICD-9-CM.
AB  - The transition to ICD-10-CM/PCS has expanded educational opportunities for
      educators and trainers who are taking on the responsibility of training coders on
      the new system. Coding education currently faces multiple challenges in the areas
      of how to train the new workforce, what might be the most efficient method of
      providing that training, how much retraining of the current workforce with ICD-9
      CM training will be required, and how to meet the national implementation
      deadline of 2014 in the most efficacious manner. This research sought to identify
      if there was a difference between a group of participants with no knowledge of
      ICD-9-CM and those with some knowledge of ICD-9-CM in scores on an ICD-10-CM/PCS
      quiz. Results indicate a difference, supporting the idea of knowledge transfer
      between the systems and providing additional insight into coding education. 

PMID- 23861678
TI  - Multiobjective optimization of evacuation routes in stadium using superposed
      potential field network based ACO.
AB  - Multiobjective evacuation routes optimization problem is defined to find out
      optimal evacuation routes for a group of evacuees under multiple evacuation
      objectives. For improving the evacuation efficiency, we abstracted the evacuation
      zone as a superposed potential field network (SPFN), and we presented SPFN-based
      ACO algorithm (SPFN-ACO) to solve this problem based on the proposed model. In
      Wuhan Sports Center case, we compared SPFN-ACO algorithm with HMERP-ACO algorithm
      and traditional ACO algorithm under three evacuation objectives, namely, total
      evacuation time, total evacuation route length, and cumulative congestion degree.
      The experimental results show that SPFN-ACO algorithm has a better performance
      while comparing with HMERP-ACO algorithm and traditional ACO algorithm for
      solving multi-objective evacuation routes optimization problem. 

PMID- 23861679
TI  - Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary
      Syndrome.
AB  - Background. We previously found that expression of SET gene was up-regulated in
      polycystic ovaries by using microarray. It suggested that SET may be an
      attractive candidate regulator involved in the pathophysiology of polycystic
      ovary syndrome (PCOS). In this study, expression and cellular localization of SET
      protein were investigated in human polycystic and normal ovaries. Method. Ovarian
      tissues, six normal ovaries and six polycystic ovaries, were collected during
      transsexual operation and surgical treatment with the signed consent form. The
      cellular localization of SET protein was observed by immunohistochemistry. The
      expression levels of SET protein were analyzed by Western Blot. Result. SET
      protein was expressed predominantly in the theca cells and oocytes of human
      ovarian follicles in both PCOS ovarian tissues and normal ovarian tissues. The
      level of SET protein expression in polycystic ovaries was triple higher than that
      in normal ovaries (P < 0.05). Conclusion. SET was overexpressed in polycystic
      ovaries more than that in normal ovaries. Combined with its localization in theca
      cells, SET may participate in regulating ovarian androgen biosynthesis and the
      pathophysiology of hyperandrogenism in PCOS. 

PMID- 23861680
TI  - Seeking out high risk population: the prevalence characteristics and outcome of
      diabetic patients of arab ethnicity hospitalized in internal medical and acute
      coronary units in Israel.
AB  - Aims. To seek high risk population for diabetes and to improve their health care
      by investigating the characteristics and outcome of hospitalization in hospitals
      with predominant Arab patients in Northern Israel. Methods. Retrospective
      analysis of the prevalence of diabetes and the outcome of diabetic in comparison
      to nondiabetic patients hospitalized in the internal medicine and intensive
      cardiac units in two major hospitals with one-year postdischarge data between
      1.1.2009 and 31.12.2009. Results. Thirty-nine percent of the patients were
      diagnosed with diabetes. The preponderance of women in the diabetes group was
      noted. Diabetic patients had an increase in the duration of hospitalization (P =
      0.0008), with one hospital having a high readmission rate for the diabetic
      patients. The average glycemia during hospitalization exceeded the recommended
      threshold of 180 mg% without major changes in the therapeutic regimens in
      comparison to preadmission regimens. Conclusions. Arab populations, women in
      particular, in westernizing societies are at high risk for diabetes which
      exemplifies as high rate of patients with diabetes among hospitalized patients.
      Areas for intervention during hospitalization and at predischarge have been
      identified to improve health outcomes and prevent readmissions. 

PMID- 23861681
TI  - Relation of visceral and subcutaneous adipose tissue to bone mineral density in
      chinese women.
AB  - The relationship between adipose and bone tissues is still being debated. The
      purpose of our study was to evaluate whether the distribution and volume of
      abdomen adipose tissue are correlated to trabecular bone mineral density in the
      lumbar spine. In this cross-sectional study, 320 Chinese women, being divided
      into two groups according to age >=55 years and <55 years, were evaluated with
      quantitative computed tomography (QCT) of the spine to simultaneously evaluate
      the average trabecular BMD of L2-L4, VAT, and SAT. Possible covariates of height,
      weight, age, and comorbidities were considered. In the <55-year-old sample,
      multiple linear regression analyses indicated that VAT volume was negatively
      correlated to trabecular BMD (P value = 0.0003) and SAT volume had no correlation
      to trabecular BMD. In contrast, there was no significant correlation between VAT
      or SAT and BMD in the >=55-year-old sample. Our results indicate that high VAT
      volume is associated with low BMD in Chinese women aged <55 years and SAT has no
      relation with BMD. 

PMID- 23861682
TI  - Mechanism of body weight reducing effect of oral boric Acid intake.
AB  - Objective. The effect of oral boric acid intake on reducing body weight has been
      previously demonstrated although the mechanism has been unclear. This research
      study reveals the mechanism. Subjects. Twelve mice were used, in groups of six
      each in the control and study groups. For five days, control group mice drank
      standard tap water while during the same time period the study group mice drank
      tap water which contains 0.28 mg/250 mL boric acid. After a 5-day period, gene
      expression levels for uncoupling proteins (UCPs) in the white adipose tissue
      (WAT), brown adipose tissue (BAT), and skeletal muscle tissue (SMT) and total
      body weight changes were analyzed. Results. Real time PCR analysis revealed no
      significant change in UCP3 expressions, but UCP2 in WAT (P: 0.0317), BAT (P:
      0.014), and SMT (P: 0.0159) and UCP1 in BAT (P: 0.026) were overexpressed in the
      boric acid group. In addition, mice in the boric acid group lost body weight
      (mean 28.1%) while mice in the control group experienced no weight loss but a
      slight weight gain (mean 0.09%, P < 0.001). Conclusion. Oral boric acid intake
      causes overexpression of thermogenic proteins in the adipose and skeletal muscle
      tissues. Increasing thermogenesis through UCP protein pathway results in the
      accelerated lipolysis and body weight loss. 

PMID- 23861683
TI  - Parameters That May Be Used for Predicting Failure during Endoscopic Retrograde
      Cholangiopancreatography.
AB  - Aim. Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used for
      the diagnosis and treatment of hepatic, biliary tract, and pancreatic disorders.
      However, failure during cannulation necessitates other interventions. The aim of
      this study was to establish parameters that can be used to predict failure during
      ERCP. Methods. A total of 5884 ERCP procedures performed on 5079 patients,
      between 1991 and 2006, were retrospectively evaluated. Results. Cannulation was
      possible in 4482 (88.2%) patients. For each one-year increase in age, the
      cannulation failure rate increased by 1.01-fold (P = 0.002). A history of
      previous hepatic biliary tract surgery caused the cannulation failure rate to
      decrease by 0.487-fold (P < 0.001). A tumor infiltrating the ampulla, the
      presence of pathology obstructing the gastrointestinal passage, and peptic ulcer
      increased the failure rate by 78-, 28-, and 3.47-fold, respectively (P < 0.001).
      Conclusions.Patient gender and duodenal diverticula do not influence the success
      of cannulation during ERCP. Billroth II and Roux-en-Y gastrojejunostomy
      surgeries, a benign or malignant obstruction of the gastrointestinal system, and
      duodenal ulcers decrease the cannulation success rate, whereas a history of
      previous hepatic biliary tract surgery increases it. Although all endoscopists
      had equal levels of experience, statistically significant differences were
      detected among them. 

PMID- 23861684
TI  - Dental treatment needs in vancouver inner-city elementary school-aged children.
AB  - Aims. To examine the dental treatment needs of inner-city Vancouver elementary
      school-aged children and relate them to sociodemographic characteristics.
      Methods. A census sampling comprising 562 children from six out of eight eligible
      schools was chosen (response rate was 65.4%). Dental treatment needs were
      assessed based on criteria from the World Health Organization. Results. Every
      third child examined needed at least one restorative treatment. A higher
      proportion of children born outside Canada were in need of more extensive dental
      treatments such as pulp care and extractions compared to the children born in
      Canada. There were no statistically significant differences in dental treatment
      needs between age, gender, or income groups or between children with or without
      dental insurance (Chi Squared P > 0.05). The best significant predictors (Linear
      Multiple Regression, P > 0.05) of higher dental treatment needs were being born
      outside Canada, gender, time of last dental visit, and family income. Having
      dental insurance did not associate with needing less treatment. Conclusion. A
      high level of unmet dental treatment needs (32%) was found in inner-city
      Vancouver elementary school-aged children. Children born outside Canada,
      particularly the ones who recently arrived to Canada, needed more extensive
      dental treatments than children born in Canada. 

PMID- 23861685
TI  - Cholestatic hepatitis with small duct injury associated with celecoxib.
AB  - Drug-induced liver injury (DILI) is a common clinical entity but is underreported
      due to various reasons. Cyclooxygenase-2 inhibitors like Celecoxib have been
      proven to be associated with lesser incidence of adverse drug reactions compared
      to other nonsteroidal anti-inflammatory drugs (NSAID). However, Celecoxib has
      been rarely reported to be associated with cholestasis and hepatitis. We present
      a young Hispanic female presented with cholestatic liver chemistries who has been
      taking Celecoxib for 3 weeks. Extensive workup did not support diagnosis of
      viral, autoimmune, or metabolic liver diseases. Liver biopsy revealed findings
      suggestive of secondary sclerosing cholangitis. Imaging studies were negative for
      large duct involvement, and endoscopy ruled out inflammatory bowel disease. Liver
      chemistries normalized after cessation of medication. We recommend that physician
      should be aware of this rare complication when prescribing Celecoxib. 

PMID- 23861686
TI  - Alport's Syndrome in Pregnancy.
AB  - Background. Alport's syndrome is an X-linked hereditary disorder affecting the
      glomerular basement membrane associated with ocular and hearing defects. In
      women, the disease is much less severe compared to that in men. However, women
      with Alport's syndrome can have an accelerated form of their disease during
      pregnancy with worsening of kidney function and can also develop preeclampsia.
      There are only four described cases of Alport's syndrome in pregnancy. Case
      Presentation. 20-year-old woman with a history of Alport's syndrome, which during
      pregnancy worsened resulting in hypertension, proteinuria, and acute kidney
      injury. Fortunately, there was complete resolution of the proteinuria and kidney
      injury with delivery, and the patient did not require any renal replacement
      therapy. Conclusion. One of the four reported cases had an accelerated form of
      the disease during pregnancy with rapid progression of kidney injury and end
      stage renal disease. There are no definite guidelines to monitor these patients
      during pregnancy. Further studies are required to understand the exact
      pathophysiology of kidney damage that occurs in pregnant women with Alport's
      syndrome. This may give us some insight into the prognostic predictors, so that
      we can monitor these women more thoroughly and prevent adverse outcomes. 

PMID- 23861687
TI  - Irregular Migration as a Potential Source of Malaria Reintroduction in Sri Lanka
      and Use of Malaria Rapid Diagnostic Tests at Point-of-Entry Screening.
AB  - Background. We describe an irregular migrant who returned to Sri Lanka after a
      failed people smuggling operation from West Africa. Results. On-arrival screening
      by Anti-Malaria Campaign (AMC) officers using a rapid diagnostic test (RDT)
      (CareStart Malaria HRP2/PLDH) indicated a negative result. On day 3 after
      arrival, he presented with fever and chills but was managed as dengue (which is
      hyperendemic in Sri Lanka). Only on day 7, diagnosis of Plasmodium falciparum
      malaria was made by microcopy and CareStart RDT. The initially negative RDT was
      ascribed to a low parasite density. Irregular migration may be an unrecognized
      source of malaria reintroduction. Despite some limitations in detection, RDTs
      form an important point-of-entry assessment. As a consequence of this case, the
      AMC is now focused on repeat testing and close monitoring of all irregular
      migrants from malaria-endemic zones. Conclusion. The present case study
      highlights the effective collaboration and coordination between inter
      governmental agencies such as IOM and the Ministry of Health towards the goals of
      malaria elimination in Sri Lanka. 

PMID- 23861688
TI  - Hepatocyte growth factor-loaded biomaterials for mesenchymal stem cell
      recruitment.
AB  - Human adult mesenchymal stem cells (MSC) can be readily harvested from bone
      marrow through aspiration. MSC are involved in tissue regeneration and repair,
      particularly in wound healing. Due to their high self-renewal capacity and
      excellent differentiation potential in vitro, MSC are ideally suited for
      regenerative medicine. The complex interactions of MSC with their environment and
      their influence on the molecular and functional levels are widely studied but not
      completely understood. MSC secrete, for example, hepatocyte growth factor (HGF),
      whose concentration is enhanced in wounded areas and which is shown to act as a
      chemoattractant for MSC. We produced HGF-loaded biomaterials based on collagen
      and fibrin gels to develop a recruitment system for endogenous MSC to improve
      wound healing. Here, we report that HGF incorporated into collagen or fibrin gels
      leads to enhanced and directed MSC migration in vitro. HGF-loaded biomaterials
      might be potentially used as in vivo wound dressings to recruit endogenous MSC
      from tissue-specific niches towards the wounded area. This novel approach may
      help to reduce costly multistep procedures of cell isolation, in vitro culture,
      and transplantation usually used in tissue engineering. 

PMID- 23861689
TI  - Maternal BMI, IGF-I Levels, and Birth Weight in African American and White
      Infants.
AB  - At birth, elevated IGF-I levels have been linked to birth weight extremes; high
      birth weight and low birth weight are risk factors for adult-onset chronic
      diseases including obesity, cardiovascular disease, and type 2 diabetes. We
      examined associations between plasma IGF-I levels and birth weight among infants
      born to African American and White obese and nonobese women. Prepregnancy weight
      and height were assessed among 251 pregnant women and anthropometric measurements
      of full term infants (>=37 weeks of gestation) were taken at birth. Circulating
      IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression
      models were utilized to examine associations between birth weight and high IGF-I,
      using the bottom two tertiles as referents. Compared with infants with lower IGF
      I levels (<=3rd tertile), those with higher IGF-I levels (>3rd tertile) were 130
      g heavier at birth, (beta-coefficient = 230, se = 58.0, P = 0.0001), after
      adjusting for gender, race/ethnicity, gestational age, delivery route, maternal
      BMI and smoking. Stratified analyses suggested that these associations are more
      pronounced in infants born to African American women and women with BMI >=30
      kg/m(2); the cross product term for IGF-I and maternal BMI was statistically
      significant (P <= 0.0004). Our findings suggest that the association between IGF
      I levels and birth weight depends more on maternal obesity than African American
      race/ethnicity. 

PMID- 23861690
TI  - Impact of adiponectin overexpression on allergic airways responses in mice.
AB  - Obesity is an important risk factor for asthma. Obese individuals have decreased
      circulating adiponectin, an adipose-derived hormone with anti-inflammatory
      properties. We hypothesized that transgenic overexpression of adiponectin would
      attenuate allergic airways inflammation and mucous hyperplasia in mice. To test
      this hypothesis, we used mice overexpressing adiponectin (Adipo Tg). Adipo Tg
      mice had marked increases in both serum adiponectin and bronchoalveolar lavage
      (BAL) fluid adiponectin. Both acute and chronic ovalbumin (OVA) sensitization and
      challenge protocols were used. In both protocols, OVA-induced increases in total
      BAL cells were attenuated in Adipo Tg versus WT mice. In the acute protocol, OVA
      induced increases in several IL-13 dependent genes were attenuated in Adipo Tg
      versus WT mice, even though IL-13 per se was not affected. With chronic exposure,
      though OVA-induced increases in goblet cells numbers per millimeter of basement
      membrane were greater in Adipo Tg versus WT mice, mRNA abundance of mucous genes
      in lungs was not different. Also, adiponectin overexpression did not induce M2
      polarization in alveolar macrophages. Our results indicate that adiponectin
      protects against allergen-induced inflammatory cell recruitment to the airspaces,
      but not development of goblet cell hyperplasia. 

PMID- 23861691
TI  - Effect of the environmental stimuli upon the human body in winter outdoor thermal
      environment.
AB  - In order to manage the outdoor thermal environment with regard to human health
      and the environmental impact of waste heat, quantitative evaluations are
      indispensable. It is necessary to use a thermal environment evaluation index. The
      purpose of this paper is to clarify the relationship between the psychological
      thermal responses of the human body and winter outdoor thermal environment
      variables. Subjective experiments were conducted in the winter outdoor
      environment. Environmental factors and human psychological responses were
      measured. The relationship between the psychological thermal responses of the
      human body and the outdoor thermal environment index ETFe (enhanced conduction
      corrected modified effective temperature) in winter was shown. The variables
      which influence the thermal sensation vote of the human body are air temperature,
      long-wave thermal radiation and short-wave solar radiation. The variables that
      influence the thermal comfort vote of the human body are air temperature,
      humidity, short-wave solar radiation, long-wave thermal radiation, and heat
      conduction. Short-wave solar radiation, and heat conduction are among the winter
      outdoor thermal environment variables that affect psychological responses to
      heat. The use of thermal environment evaluation indices that comprise short-wave
      solar radiation and heat conduction in winter outdoor spaces is a valid approach.

PMID- 23861692
TI  - A human/murine chimeric fab antibody neutralizes anthrax lethal toxin in vitro.
AB  - Human anthrax infection caused by exposure to Bacillus anthracis cannot always be
      treated by antibiotics. This is mostly because of the effect of the remaining
      anthrax toxin in the body. Lethal factor (LF) is a component of lethal toxin
      (LeTx), which is the major virulence of anthrax toxin. A murine IgG monoclonal
      antibody (mAb) against LF with blocking activity (coded LF8) was produced in a
      previous study. In this report, a human/murine chimeric Fab mAb (coded LF8-Fab)
      was developed from LF8 by inserting murine variable regions into human constant
      regions using antibody engineering to reduce the incompatibility of the murine
      antibody for human use. The LF8-Fab expressed in Escherichia coli could
      specifically identify LF with an affinity of 3.46 * 10(7) L/mol and could
      neutralize LeTx with an EC50 of 85  MU g/mL. Even after LeTx challenge at various
      time points, the LF8-Fab demonstrated protection of J774A.1 cells in vitro. The
      results suggest that the LF8-Fab might be further characterized and potentially
      be used for clinical applications against anthrax infection. 

PMID- 23861693
TI  - New insights into the role of the immune microenvironment in breast carcinoma.
AB  - Recently, immune edition has been recognized as a new hallmark of cancer. In this
      respect, some clinical trials in breast cancer have reported imppressive outcomes
      related to laboratory immune findings, especially in the neoadjuvant and
      metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and
      their subtypes, tumor-associated macrophages (TAM) and myeloid-derived
      suppressive cells (MDSC) seem bona fide prognostic and even predictive
      biomarkers, that will eventually be incorporated into diagnostic and therapeutic
      algorithms of breast cancer. In addition, the complex interaction of
      costimulatory and coinhibitory molecules on the immune synapse and the different
      signals that they may exert represent another exciting field to explore. In this
      review we try to summarize and elucidate these new concepts and knowledge from a
      translational perspective focusing on breast cancer, paying special attention to
      those aspects that might have more significance in clinical practice and could be
      useful to design successful therapeutic strategies in the future. 

PMID- 23861695
TI  - A systematic review and meta-analysis of buyang huanwu decoction in animal model
      of focal cerebral ischemia.
AB  - Buyang Huanwu Decoction (BHD) is a well-known Chinese herbal prescription for
      ischemic stroke. The objective of this systematic review and meta-analysis is to
      provide the current evidence for neuroprotective effects of BHD and its possible
      mechanisms in animal models of focal ischemia. A systematic literature search,
      through October 2012, was performed using six databases. The outcome measures
      assessed were infarct size and/or neurological score. Fifty-six studies with 1270
      animals that met the inclusion criteria were identified. The median score for
      methodological quality was 3 with a range of 2 to 6. Compared with vehicle or no
      treatment controls, BHD gave a 37% improvement in outcome for all doses ranging
      from 1.0 g/kg to 60 g/kg at each time point that BHD was administered (P < 0.01).
      Efficacy was higher in mouse models that utilized suture occlusion and temporary
      ischemia. The neuroprotective effects of BHD are involved in multiple mechanisms
      and act upon multiple cell types. In conclusion, BHD possesses substantial
      neuroprotective effects in experimental stroke probably as a result of the
      multitarget therapy strategy typically utilized in traditional Chinese medicine.
      Future research should examine the presence of possible experimental bias and an
      in-depth study of herbal compound preparations. 

PMID- 23861694
TI  - Respiratory-related hospitalizations following prophylaxis in the Canadian
      registry for palivizumab (2005-2012) compared to other international registries.
AB  - Respiratory syncytial virus (RSV) infection occurs commonly in infants aged <=2
      years, and severe infection results in hospitalization with accompanying
      morbidity and mortality. Palivizumab has been available for prophylaxis for the
      past 15 years. Prospective data on patients who received palivizumab from 2005 to
      2012 has been assembled in the Canadian registry (CARESS) to document
      utilization, compliance, and health outcomes in both hospital and community
      settings. Long-term data is necessary to evaluate the impact of palivizumab on
      the incidence of RSV infections, minimize healthcare resources, and identify
      which infant subpopulations are receiving prophylaxis. A database search was also
      conducted for similar information from published registries, and hospitalization
      rates were compared to results from randomized clinical trials (RCTs).Overall
      hospitalization rates (percent; range) for respiratory-related illnesses and RSV
      specific infection in infants who meet standard indications for prophylaxis were
      6.6 (3.3-7.7) and 1.55 (0.3-2.06), respectively, in CARESS, which closely aligns
      with registry data from 4 other countries, despite the former comprising the
      largest cohort of complex patients internationally. Overall RSV-related
      hospitalization rates were lower across registries compared to equivalent
      patients in RCTs. Registry data provides valuable information regarding real
      world experience with palivizumab, while facilitating the genesis of new research
      themes. 

PMID- 23861696
TI  - Efficacy and safety of medicinal plants or related natural products for
      fibromyalgia: a systematic review.
AB  - To assess the effects of medicinal plants (MPs) or related natural products
      (RNPs) on fibromyalgia (FM) patients, we evaluate the possible benefits and
      advantages of MP or RNP for the treatment of FM based on eight randomized placebo
      controlled trials (RCTs) involving 475 patients. The methodological quality of
      all studies included was determined according to JADAD and "Risk of Bias" with
      the criteria in the Cochrane Handbook for Systematic Reviews of Interventions
      5.1.0. Evidence suggests significant benefits of MP or RNP in sleep disruption,
      pain, depression, joint stiffness, anxiety, physical function, and quality of
      life. Our results demonstrated that MP or RNP had significant effects on
      improving the symptoms of FM compared to conventional drug or placebo; longer
      tests are required to determine the duration of the treatment and characterize
      the long-term safety of using MP, thus suggesting effective alternative therapies
      in the treatment of pain with minimized side effects. 

PMID- 23861697
TI  - Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana.
AB  - Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate
      parasites of the genus Leishmania. In the search for more effective agents
      against these parasites, the identification of molecular targets has been
      attempted to ensure the efficiency of drugs and to avoid collateral damages on
      the host's cells. In this work, we have investigated some of the mechanisms of
      action of a group of natural sesquiterpene lactones that are effective against
      Leishmania mexicana mexicana promastigotes. We first observed that the
      antiproliferative effect of mexicanin I (Mxc), dehydroleucodine (DhL),
      psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by
      1.5 mM reduced glutathione. The reducing agent was also able to reverse the early
      effect of the compounds, suggesting that lactones may react with intracellular
      sulfhydryl groups. Moreover, we have shown that all the sesquiterpene lactones,
      except Psi C, significantly decreased the endogenous concentration of glutathione
      within the parasite. Consistent with these findings, the active sesquiterpene
      lactones increased between 2.7 and 5.4 times the generation of ROS by parasites.
      These results indicate that the induction of oxidative stress is at least one of
      the mechanisms of action of DhL, Mxc, and Psi on parasites while Psi C would act
      by another mechanism. 

PMID- 23861698
TI  - Evaluating meridian-sinew release therapy for the treatment of knee
      osteoarthritis.
AB  - Objective. In recent years, public health experts have concluded that the impact
      of osteoarthritis is equal in magnitude to that of cardiovascular disease.
      Osteoarthritis of the knee is prevalent in the elderly population; however, there
      are currently no effective treatments for this condition. In this study, we
      investigated the efficacy of "meridian-sinew release," a newly developed
      technique which entails using a meridian-sinew scope and a meridian-sinew knife
      to treat osteoarthritis of the knee. Methods. Patients (N = 90) with knee
      osteoarthritis were prospectively randomized to meridian-sinew release therapy,
      acupuncture therapy, or drug therapy groups, respectively. Outcome evaluation
      included pain, stiffness, physiological function, total symptom score, and
      overall changes in the condition. Results. After 12 weeks, patients' general
      assessment (GA) and doctors' general assessment (GA) of the condition were not
      significantly different among the three groups. However, significant differences
      in primary endpoint pain, joint stiffness, and total symptom score were found
      between the meridian-sinew group and the acupuncture group and between the
      meridian-sinew group and the control group (P < 0.05). No adverse events occurred
      during the trial. Conclusion. Our study suggests that meridian-sinew release
      therapy can improve knee osteoarthritis, alleviate joint pain, and improve
      functional movement disorder. It is a safe and effective treatment for knee
      osteoarthritis. 

PMID- 23861699
TI  - Influence of the toothpaste with brazilian ethanol extract propolis on the oral
      cavity health.
AB  - Propolis-based therapeutic agents represent this potential for the development of
      new drugs in dental care. The aim of a clinical-cohort study was to determine the
      influence of application of toothpaste enriched with Brazilian extract of
      propolis (EEP) on health status of oral cavity. Laboratory analysis was conducted
      in order to assess the chemical composition of EEP including total phenolic
      compounds, the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity,
      ABTS radical cation scavenging activity, and FRAP assay. Clinical research
      involved two groups of subjects comprising 32 adult patients, with assessment
      based on the preliminary evaluation of the state of their marginal periodontium.
      The investigation of oral health indices API, OHI, and SBI and microbiological
      examination of oral microflora were also carried out. Results obtained indicated
      time-dependent microbial action of EEP at 50 mg/L concentration, with
      antimicrobial activity against Gram-positive bacteria. The total decrease of API,
      OHI, and SBI mean values was observed. Hygienic preparations with 3% content of
      Brazilian ethanol extract of green propolis (EEP) efficiently support removal of
      dental plaque and improve the state of marginal periodontium. 

PMID- 23861700
TI  - Therapeutic effects of saireito (chai-ling-tang), a traditional Japanese herbal
      medicine, on lymphedema caused by radiotherapy: a case series study.
AB  - Despite the development of radiotherapy machines and technologies, a proportion
      of patients suffer from radiation-induced lymphedema. Saireito (SRT) is a
      traditional Japanese herbal medicine that has been used for treating edema and
      inflammation in conditions such as nephritic disease. This study investigated the
      effect of SRT on lymphedema caused by radiotherapy. Four patients were treated
      with SRT at a dose of 9 g/day. The severity of lymphedema was evaluated using the
      Common Terminology Criteria for Adverse Events version 4 and Numerical Rating
      Scale before and after SRT treatment. After the treatment with SRT, 2 of 4
      patients (50%) showed apparent improvement in lymphedema. One of the cases had
      difficulty in wearing the custom-made thermoplastic cast, but after SRT
      administration, he could wear the mask easily. One case decided to stop taking
      SRT 3 days after initiation because cough and fever appeared. In conclusion, it
      is important to control the side effects of radiotherapy, which leads to improved
      tumor control rates. Prospective randomized studies are necessary to confirm the
      findings of this case series study. 

PMID- 23861701
TI  - The Phytochemical Shikonin Stimulates Epithelial-Mesenchymal Transition (EMT) in
      Skin Wound Healing.
AB  - Although various pharmacological activities of the shikonins have been
      documented, understanding the hierarchical regulation of these diverse
      bioactivities at the genome level is unsubstantiated. In this study, through
      cross examination between transcriptome and microRNA array analyses, we predicted
      that topical treatment of shikonin in vivo affects epithelial-mesenchymal
      transition (EMT) and the expression of related microRNAs, including 200a, 200b,
      200c, 141, 205, and 429 microRNAs, in mouse skin tissues. In situ
      immunohistological analyses further demonstrated that specific EMT regulatory
      molecules are enhanced in shikonin-treated epidermal tissues. RT-PCR analyses
      subsequently confirmed that shikonin treatment downregulated expression of
      microRNA-205 and other members of the 200 family microRNAs. Further, expression
      of two RNA targets of the 200 family microRNAs in EMT regulation, Sip1 (Zeb2) and
      Tcf8 (Zeb1), was consistently upregulated by shikonin treatment. Enhancement of
      these EMT activities was also detected in shikonin-treated wounds, which repaired
      faster than controls. These results suggest that topical treatment with shikonin
      can confer a potent stimulatory effect on EMT and suppress the expression of the
      associated microRNAs in skin wound healing. Collectively, these cellular and
      molecular data provide further evidence in support of our previous findings on
      the specific pharmacological effects of shikonin in wound healing and immune
      modulation. 

PMID- 23861702
TI  - The Effects of Banha-sasim-tang on Dyspeptic Symptoms and Gastric Motility in
      Cases of Functional Dyspepsia: A Randomized, Double-Blind, Placebo-Controlled,
      and Two-Center Trial.
AB  - Introduction. Functional dyspepsia (FD) is highly prevalent, and no standard
      treatments exist for this condition. Herbal prescriptions are widely used to
      treat FD. In traditional Korean medicine, Banha-sasim-tang (BST) is a famous
      herbal prescription for dyspepsia. This study aimed to evaluate the efficacy of
      BST and to examine the relationship between gastric slow waves and dyspeptic
      symptoms. Materials and Methods. In total, 100 FD patients were recruited; BST or
      placebo was administered for 6 weeks. The gastrointestinal symptom scale, FD
      related quality of life scale, and frequency or power variables regarding gastric
      slow waves were measured at 0, 6, and 14 weeks. Results. There were no
      significant differences in the overall dyspeptic symptoms or quality of life
      between the BST and placebo groups. However, early satiety was significantly
      improved in the BST group (P = 0.009, at 6 weeks by intention-to-treat analysis).
      Abnormal gastric dysrhythmias and power ratios were also significantly improved
      by BST. Conclusion. BST had no significant effects on FD. However, early satiety
      appeared to improve after BST administration. Electrogastrography may be a useful
      technique for assessing changes in gastric motility dysfunction after
      interventions for FD. Further investigation focused on specific symptoms or
      subtypes of FD is required. 

PMID- 23861703
TI  - ATP release from mast cells by physical stimulation: a putative early step in
      activation of acupuncture points.
AB  - In Chinese medicine acupuncture points are treated by physical stimuli to
      counteract various diseases. These stimuli include mechanical stress as applied
      during the needle manipulation or tuina, high temperatures as applied during
      moxibustion, and red laser light applied during laser acupuncture. This study
      aimed to investigate cellular responses to stimuli that might occur in the tissue
      of acupuncture points. Since they have a characteristically high density of mast
      cells that degranulate in response to acupuncture, we asked whether these
      processes lead to ATP release. We tested in in vitro experiments on mast cells of
      the human mast-cell line HMC-1 the effects of the physical stimuli; mechanical
      stress was applied by superfusion of the cells with hypotonic solution, heat was
      applied by incubation of the cells at 52 degrees C, and red laser light of 657 nm
      was used for irradiation. We demonstrate that all the stimuli induce ATP release
      from model human mast HMC-1 cells, and this release is associated with an
      intracellular free Ca(2+) rise. We hypothesize that ATP released from mast cells
      supplements the already known release of ATP from keratinocytes and, by acting on
      P2X receptors, it may serve as initial mediator of acupuncture-induced analgesia.

PMID- 23861704
TI  - A Comparison Study of Growth Factor Expression following Treatment with
      Transcutaneous Electrical Nerve Stimulation, Saline Solution, Povidone-Iodine,
      and Lavender Oil in Wounds Healing.
AB  - This study compared the effects of transcutaneous electrical nerve stimulation
      (TENS), saline solution (SS), povidone-iodine (PI), and lavender oil (Lavandula
      angustifolia) through expression of growth factors in a rat model of wound
      healing. Six experimental groups were established, each containing 8 rats: a
      healthy group with no incision wounds, an incision-control group, an incision and
      TENS group, an incision and SS group, an incision and PI group, and an incision
      and lavender oil group. Experiments continued for 5 days, after which the skin in
      the excision area was removed. Tissue concentrations of epidermal growth factor
      (EGF) and platelet-derived growth factor (PDGF)-A were measured using enzyme
      linked immunosorbent assay (ELISA). Tissue expressions of EGF, PDGF-A, and
      fibroblast growth factor (FGF)-2 were determined using immunohistochemistry.
      Wound closure progressed more rapidly in the TENS and lavender oil groups than in
      the control and other study groups. In particular, PDGF-A expressions in the
      dermis and EGF expression in the epidermis were significantly intense in the TENS
      group (P < 0.05). In addition, ELISA levels of growth factors such as PDGF-A and
      EGF were significantly higher in TENS group compared to the control group (P <
      0.05). These immunohistochemical and ELISA results suggest that TENS may improve
      wound healing through increasing growth factors in the dermis and epidermis more
      than other topical applications. 

PMID- 23861705
TI  - Laser Acupuncture: Two Acupoints (Baihui, Neiguan) and Two Modalities of Laser
      (658 nm, 405 nm) Induce Different Effects in Neurovegetative Parameters.
AB  - There are only few scientific publications dealing with the basic investigation
      of the effects of only one or two acupoints or comparing one single point with
      another single point, using different stimulation methods in the same persons.
      The aim of this needle-controlled, randomized crossover study was to investigate
      the neurovegetative parameters heart rate (HR) and heart rate variability (HRV)
      using two different acupoints, Baihui (GV20) and Neiguan (PC6), in separate
      sessions. We investigated 11 healthy volunteers (3 m, 8 f) with a mean age +/- SD
      of 22.9 +/- 2.8 years. The two acupoints were stimulated for 10 minutes each with
      manual needle acupuncture, red laser acupuncture (658 nm), and violet laser
      acupuncture (405 nm), in randomized order. Needle and red laser stimulation of
      the Baihui acupoint decreased HR significantly. Only violet laser stimulation at
      the Neiguan acupoint induced a significant increase of total HRV. Further studies
      using other neurovegetative parameters and more volunteers are necessary to
      confirm the preliminary results. 

PMID- 23861706
TI  - The neuroprotective effect of gugijihwang-tang on trimethyltin-induced memory
      dysfunction in the rat.
AB  - Gugijihwang-Tang (the herbal formula PM012), a decoction consisting of several
      herbs including Rehmanniae Radix Preparata, has been widely used as herbal
      treatment for dementia. In order to investigate the neuroprotective action of
      this prescription, we examined the effect of Gugijihwang-Tang on learning and
      memory using the Morris water maze and [F-18]FDG micro PET neuroimaging
      technique. After injection of trimethyltin (TMT, 8.0 mg/kg, i.p.), which is a
      potent toxicant that selectively kills cells in the central nervous system, rats
      were administered Gugijihwang-Tang (100 mg/kg, p.o.) daily for two weeks,
      followed by the Morris water maze tasks and [F-18]FDG micro PET neuroimaging. In
      Gugijihwang-Tang administered TMT-treated rats, they showed improved learning and
      memory abilities in water maze tasks and glucose metabolism, suggesting that
      Gugijihwang-Tang plays effectively positive role in the improvement of brain
      function including learning and memory after TMT-induced neurodegeneration. Taken
      together, our results suggested that the Gugijihwang-Tang should be useful for
      developing strategies protecting nervous system and improving brain function. 

PMID- 23861707
TI  - Virgin coconut oil prevents blood pressure elevation and improves endothelial
      functions in rats fed with repeatedly heated palm oil.
AB  - This study was performed to explore the effects of virgin coconut oil (VCO) in
      male rats that were fed with repeatedly heated palm oil on blood pressure, plasma
      nitric oxide level, and vascular reactivity. Thirty-two male Sprague-Dawley rats
      were divided into four groups: (i) control (basal diet), (ii) VCO (1.42 mL/kg,
      oral), (iii) five-times-heated palm oil (15%) (5HPO), and (iv) five-times-heated
      palm oil (15%) and VCO (1.42 mL/kg, oral) (5HPO + VCO). Blood pressure was
      significantly increased in the group that was given the 5HPO diet compared to the
      control group. Blood pressure in the 5HPO + VCO group was significantly lower
      than the 5HPO group. Plasma nitric oxide (NO) level in the 5HPO group was
      significantly lower compared to the control group, whereas in the 5HPO + VCO
      group, the plasma NO level was significantly higher compared to the 5HPO group.
      Aortic rings from the 5HPO group exhibited attenuated relaxation in response to
      acetylcholine and sodium nitroprusside as well as increased vasoconstriction to
      phenylephrine compared to the control group. Aortic rings from the 5HPO + VCO
      group showed only attenuated vasoconstriction to phenylephrine compared to the
      5HPO group. In conclusion, VCO prevents blood pressure elevation and improves
      endothelial functions in rats fed with repeatedly heated palm oil. 

PMID- 23861708
TI  - Historical Review about Research on "Bonghan System" in China.
AB  - The meridian-collateral theory is the theoretical basis of acupuncture
      moxibustion therapy. Professor Bonghan Kim, a professor of the Pyongyang Medical
      University of the Democratic People's Republic of Korea, claimed that he found
      the anatomical structure of meridian-collaterals, named Bonghan corpuscles (BHCs)
      and Bonghan ducts (BHDs) system or primo vascular system (PVS), in 1962. From
      1963 to 1965, researchers from our institute conducted a series of comparative
      anatomical experiments, trying to reproduce the so-called BHC- and BHD-like
      structures in different strains of animals. In the present paper, the authors
      introduced their research findings about BHC- and BHD-like structures in the
      young rabbit's umbilicus including its external appearance, ectoplasm and
      endoplasm, and about strip-like and node-like objects in the blood vessels and
      lymph vessels near the larger abdominal and cervical blood vessels and chromaffin
      tissue in the back wall of the rabbit's abdominal cavity and between the
      bilateral kidneys. In spite of existence of the BHC- and BHD-like structures in
      the rabbit, there has been no proved evidence for their association with the
      meridian-collateral system described in acupuncture medicine. In the present
      historical review, the authors also make a discussion about the significance of
      those findings. 

PMID- 23861709
TI  - Garlic-Derived S-Allylmercaptocysteine Ameliorates Nonalcoholic Fatty Liver
      Disease in a Rat Model through Inhibition of Apoptosis and Enhancing Autophagy.
AB  - Our previous study demonstrated that administration of garlic-derived antioxidant
      S-allylmercaptocysteine (SAMC) ameliorated hepatic injury in a nonalcoholic fatty
      liver disease (NAFLD) rat model. Our present study aimed to investigate the
      mechanism of SAMC on NAFLD-induced hepatic apoptosis and autophagy. Adult female
      rats were fed with a high-fat diet for 8 weeks to develop NAFLD with or without
      intraperitoneal injection of 200 mg/kg SAMC for three times per week. During
      NAFLD development, increased apoptotic cells and caspase-3 activation were
      observed in the liver. Increased apoptosis was modulated through both intrinsic
      and extrinsic apoptotic pathways. NAFLD treatment also enhanced the expression of
      key autophagic markers in the liver with reduced activity of LKB1/AMPK and
      PI3K/Akt pathways. Increased expression of proapoptotic regulator p53 and
      decreased activity of antiautophagic regulator mTOR were also observed.
      Administration of SAMC reduced the number of apoptotic cells through
      downregulation of both intrinsic and extrinsic apoptotic mechanisms. SAMC also
      counteracted the effects of NAFLD on LKB1/AMPK and PI3K/Akt pathways. Treatment
      with SAMC further enhanced hepatic autophagy by regulating autophagic markers and
      mTOR activity. In conclusion, administration of SAMC during NAFLD development in
      rats protects the liver from chronic injury by reducing apoptosis and enhancing
      autophagy. 

PMID- 23861710
TI  - The characteristics of action potentials in primo vessels and the effects of
      acetylcholine injection to the action potentials.
AB  - In a previous study, we found that Primo vessels generate different action
      potentials in smooth muscles, but this study compared the pulse shape to
      distinguish the two tissues. Thus, a more sophisticated extracellular experiment
      was performed in this study using an acetylcholine injection; we then observed
      changes in the amplitude, FWHM (full width at half maximum), and period to
      explore Primo vessel function. A third type of pulse was recorded for Primo
      vessels. We observed fast depolarizing and repolarizing phases for this pulse.
      Further, its FWHM was 30 ms between smooth muscles and neurons. Acetylcholine
      affected only the period. The amplitude and FWHM were consistent after injection.
      Primo-vessels generated action potentials at twice the frequency after injection.
      From the results, we speculate that Primo-vessels perform a role in transferring
      signals in a different manner, which may be relevant for acupuncture treatment. 

PMID- 23861711
TI  - Inhibition of Metastatic Potential in Breast Carcinoma In Vivo and In Vitro
      through Targeting VEGFRs and FGFRs.
AB  - Angiogenesis and lymphangiogenesis are considered to play key roles in tumor
      metastasis. Targeting receptor tyrosine kinases essentially involved in the
      angiogenesis and lymphangiogenesis would theoretically prevent cancer metastasis.
      However, the optimal multikinase inhibitor for metastasis suppression has yet to
      be developed. In this study, we evaluated the effect of NSTPBP 0100194-A (194-A),
      a multikinase inhibitor of vascular endothelial growth factor receptors
      (VEGFRs)/fibroblast growth factor receptors (FGFRs), on lymphangiogenesis and
      angiogenesis in a mammary fat pad xenograft model of the highly invasive breast
      cancer cell line 4T1-Luc(+). We investigated the biologic effect of 194-A on
      various invasive breast cancer cell lines as well as endothelial and lymphatic
      endothelial cells. Intriguingly, we found that 194-A drastically reduced the
      formation of lung, liver, and lymph node metastasis of 4T1-Luc(+) and decreased
      primary tumor growth. This was associated with significant reductions in
      intratumoral lymphatic vessel length (LVL) and microvessel density (MVD). 194-A
      blocked VEGFRs mediated signaling on both endothelial and lymphatic endothelial
      cells. Moreover, 194-A significantly inhibited the invasive capacity induced by
      VEGF-C or FGF-2 in vitro in both 4T1 and MDA-MB231 cells. In conclusion, these
      experimental results demonstrate that simultaneous inhibition of VEGFRs/FGFRs
      kinases may be a promising strategy to prevent breast cancer metastasis. 

PMID- 23861712
TI  - Significance of Kampo, traditional Japanese medicine, in supportive care of
      cancer patients.
AB  - The current standard treatment for cancer is a multidisciplinary therapy whereby
      various types of treatment are properly combined. Chemotherapy with multiple
      anticancer drugs is now common, and traditional, complementary, and alternative
      therapies are adopted as supportive measures. Medical care in Japan is
      distinguished by the ability for patients to access both Western and Kampo
      medical cares at the same time. There is a high degree of trust in the safety of
      Kampo therapies because they are practiced by medical doctors who are educated
      with fundamental diagnosis of Western medicine. Highly reliable clinical studies
      are being published, demonstrating that palliative or supportive care for cancer
      patients using Kampo preparations alleviates adverse effects of chemotherapy or
      radiotherapy. This paper reports the circumstances around cancer care in Japan
      where traditional therapeutic Kampo formulas are used for patients undergoing
      cancer treatment with cutting-edge chemotherapy, specifically to alleviate
      adverse effects of anticancer drugs. 

PMID- 23861713
TI  - Effect of Angelica sinensis Polysaccharides on Osteoarthritis In Vivo and In
      Vitro: A Possible Mechanism to Promote Proteoglycans Synthesis.
AB  - This study investigated the effect of Angelica sinensis polysaccharides (APS-3c)
      on rat osteoarthritis (OA) model in vivo and rat interleukin-1-beta- (IL-1 beta 
      ) stimulated chondrocytes in vitro. APS-3c was administrated into rat OA knee
      joints and had protective effects on rat OA cartilage in vivo. Primary rat
      articular chondrocytes were cotreated with APS-3c and IL-1 beta   in vitro. 2~50 
      MU g/mL APS-3c had no effect on chondrocytes viability, whereas it increased the
      proteoglycans (PGs) synthesis inhibited by IL-1 beta . Microarray analysis showed
      that the significant changes were concentrated in the genes which were involved
      in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA
      expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1 beta but
      did not affect the mRNA expression of matrix-degrading enzymes. These results
      indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA model in
      vivo and IL-1 beta -stimulated chondrocytes in vitro, which is due to the
      promotion of the expression of aggrecan and GTs involved in PGs synthesis but not
      the inhibition of the expression of matrix-degrading enzymes. Our findings
      suggest the clinical relevance of APS-3c in the prospective of future alternative
      medical treatment for OA. 

PMID- 23861714
TI  - Integration of Different "-omics" Technologies Identifies Inhibition of the IGF1R
      Akt-mTOR Signaling Cascade Involved in the Cytotoxic Effect of Shikonin against
      Leukemia Cells.
AB  - Hematological malignancies frequently have a poor prognosis and often remain
      incurable. Drug resistance, severe side effects, and relapse are major problems
      of currently used drugs, and new candidate compounds are required for improvement
      of therapy success. The naphthoquinone shikonin derived from the Chinese
      medicinal herb, Lithospermum erythrorhizon, is a promising candidate for the next
      generation of chemotherapy. The basal cellular mechanism of shikonin is the
      direct targeting of mitochondria. Cytotoxicity screenings showed that the
      compound is particularly effective against leukemia cells suggesting an
      additional cellular mechanism. mRNA and miRNA microarrays were used to analyze
      changes in gene expression in leukemia cells after shikonin treatment and
      combined with stable-isotope dimethyl labeling for quantitative proteomics. The
      integration of bioinformatics and the three "-omics" assays showed that the PI3K
      Akt-mTOR pathway was affected by shikonin. Deregulations of this pathway are
      frequently associated with cancerogenesis, especially in a wide range of
      hematological malignancies. The effect on the PI3K-Akt-mTOR axis was validated by
      demonstrating a decreased phosphorylation of Akt and a direct inhibition of the
      IGF1R kinase activity after shikonin treatment. Our results indicate that
      inhibiting the IGF1R-Akt-mTOR signaling cascade is a new cellular mechanism of
      shikonin strengthening its potential for the treatment of hematological
      malignancies. 

PMID- 23861715
TI  - QSYQ Attenuates Oxidative Stress and Apoptosis Induced Heart Remodeling Rats
      through Different Subtypes of NADPH-Oxidase.
AB  - We aim to investigate the therapeutic effects of QSYQ, a drug of heart failure
      (HF) in clinical practice in China, on a rat heart failure (HF) model. 3 groups
      were divided: HF model group (LAD ligation), QSYQ group (LAD ligation and treated
      with QSYQ), and sham-operated group. After 4 weeks, rats were sacrificed for
      cardiac injury measurements. Rats with HF showed obvious histological changes
      including necrosis and inflammation foci, elevated ventricular remodeling markers
      levels(matrix metalloproteinases-2, MMP-2), deregulated ejection fraction (EF)
      value, increased formation of oxidative stress (Malondialdehyde, MDA), and up
      regulated levels of apoptotic cells (caspase-3, p53 and tunnel) in myocardial
      tissue. Treatment of QSYQ improved cardiac remodeling through counter-acting
      those events. The improvement of QSYQ was accompanied with a restoration of NADPH
      oxidase 4 (NOX4) and NADPH oxidase 2 (NOX2) pathways in different patterns.
      Administration of QSYQ could attenuate LAD-induced HF, and AngII-NOX2-ROS-MMPs
      pathway seemed to be the critical potential targets for QSYQ to reduce the
      remodeling. Moreover, NOX4 was another key targets to inhibit the p53 and
      Caspase3, thus to reduce the hypertrophy and apoptosis, and eventually provide a
      synergetic cardiac protective effect. 

PMID- 23861716
TI  - Total Phenolics and Total Flavonoids Contents and Hypnotic Effect in Mice of
      Ziziphus mauritiana Lam. Seed Extract.
AB  - The seeds of Ziziphus mauritiana Lam. have been traditionally used for treatment
      of various complications including insomnia and anxiety. They are popularly used
      as sedative and hypnotic drugs in China, Korea, Myanmar, Vietnam, and other Asian
      countries. However, no scientific proof on hypnotic activity of Z. mauritiana
      seeds (ZMS) was reported. In this study, the hypnotic activity of 50% ethanolic
      extract from ZMS was observed on the loss of righting reflex in mice using
      pentobarbital-induced sleep mice method. The contents of total phenolics and
      total flavonoids in the extract were also determined. The results showed that the
      50% ethanolic extract from ZMS contained total phenolics 27.62 +/- 1.43 mg gallic
      acid equivalent (GAE)/g extract and total flavonoids 0.74 +/- 0.03 mg quercetin
      equivalent (QE)/g extract. Oral administration of the extract at the dose of 200
      mg/kg significantly increased the sleeping time in mice intraperitoneally
      administered with sodium pentobarbital (50 mg/kg body weight). These results
      supported the traditional use of ZMS for the treatment of insomnia. The seeds of
      Z. mauritiana should be further developed as an alternative sedative and/or
      hypnotic product. 

PMID- 23861717
TI  - Evaluation of Antidiabetic Activity and Associated Toxicity of Artemisia afra
      Aqueous Extract in Wistar Rats.
AB  - Artemisia afra Jacq. ex Willd. is a widely used medicinal plant in South Africa
      for the treatment of diabetes. This study aimed to evaluate the hypoglycemic
      activity and possible toxicity effect of aqueous leaf extract of the herb
      administered at different dosages for 15 days in streptozotocin-induced diabetic
      rats. Administration of the extract at 50, 100, and 200 mg/kg body weight
      significantly (P < 0.05) increased body weight, decreased blood glucose levels,
      increased glucose tolerance, and improved imbalance in lipid metabolism in
      diabetic rats. These are indications of antidiabetic property of A. afra with 200
      mg/kg body weight of the extract showing the best hypoglycemic action by
      comparing favourably well with glibenclamide, a standard hypoglycemic drug. The
      extract at all dosages tested also restored liver function indices and
      haematological parameters to normal control levels in the diabetic rats, whereas
      the kidney function indices were only normalized in the diabetic animals
      administered with 50 mg/kg body weight of the extract. This investigation clearly
      showed that in addition to its hypoglycemic activity, A. afra may also protect
      the liver and blood against impairment due to diabetes. However, some kidney
      functions may be compromised at high dosages of the extract. 

PMID- 23861718
TI  - Auricular acupuncture at the "shenmen" and "point zero" points induced
      parasympathetic activation.
AB  - Purpose. Since auricular acupuncture is a diagnostic and treatment system based
      on normalizing the body's dysfunction, auricular acupuncture has been applied for
      pain relief, relaxation, and so on. These techniques would modulate the autonomic
      nerve system, thereby inducing the above-mentioned effects. The aim was to see
      the effect of auricular acupuncture applied to the "Shenmen" and "Point Zero"
      points on the postoperative heart rate variability (HRV). Methods. Twenty-six
      patients who underwent hemicolectomy under general anesthesia were randomized
      into the control or the acupuncture group. After the operation and before
      emergence, the acupuncture group received auricular acupuncture. An
      electrocardiographic unit was placed for recording the autonomic nervous
      activities. Results. The low frequency (LF)/high frequency (HF) ratio of HRV
      increased (P = 0.0007) in the control, but the ratio in the acupuncture did not
      change. There were significant differences between the ratios of the two groups
      at 3 : 00, 4 : 00, and 5 : 00. HF of the acupuncture group tended to be higher.
      HFs of the acupuncture group were significantly higher than those of the control
      group at 3 : 00, 4 : 00, and 5 : 00. Conclusion. Auricular acupuncture kept the
      LF/HF ratio at lower levels and HF at higher levels during postoperative period
      in the patients who had undergone hemicolectomy. 

PMID- 23861719
TI  - Higenamine Combined with [6]-Gingerol Suppresses Doxorubicin-Triggered Oxidative
      Stress and Apoptosis in Cardiomyocytes via Upregulation of PI3K/Akt Pathway.
AB  - Sini decoction is a well-known formula of traditional Chinese medicine, which has
      been used to treat cardiovascular disease for many years. Previously, we
      demonstrated that Sini decoction prevented doxorubicin-induced heart failure in
      vivo. However, its active components are still unclear. Thus, we investigated the
      active components of Sini decoction and their cardioprotective mechanisms in the
      in vitro neonatal rat cardiomyocytes and H9c2 cell line models of doxorubicin
      induced cytotoxicity. Our results demonstrated that treatment with higenamine or
      [6]-gingerol increased viability of doxorubicine-injured cardiomyocytes.
      Moreover, combined use of higenamine and [6]-gingerol exerted more profound
      protective effects than either drug as a single agent, with effects similar to
      those of dexrazoxane, a clinically approved cardiac protective agent. In
      addition, we found that treatment with doxorubicin reduced SOD activity,
      increased ROS generation, enhanced MDA formation, induced release of LDH, and
      triggered the intrinsic mitochondria-dependent apoptotic pathway in
      cardiomyocytes, which was inhibited by cotreatment of higenamine and [6]
      gingerol. Most importantly, the cytoprotection of higenamine plus [6]-gingerol
      could be abrogated by LY294002, a PI3K inhibitor. In conclusion, combination of
      higenamine and [6]-gingerol exerts cardioprotective effect against doxorubicin
      induced cardiotoxicity through activating the PI3K/Akt signaling pathway.
      Higenamine and [6]-gingerol may be the active components of Sini decoction. 

PMID- 23861720
TI  - Evidence-based chinese medicine for hypertension.
AB  - Hypertension is an important worldwide public -health challenge with high
      mortality and disability. Due to the limitations and concerns with current
      available hypertension treatments, many hypertensive patients, especially in
      Asia, have turned to Chinese medicine (CM). Although hypertension is not a CM
      term, physicians who practice CM in China attempt to treat the disease using CM
      principles. A variety of approaches for treating hypertension have been taken in
      CM. For seeking the best evidence of CM in making decisions for hypertensive
      patients, a number of clinical studies have been conducted in China, which has
      paved the evidence-based way. After literature searching and analyzing, it
      appeared that CM was effective for hypertension in clinical use, such as Chinese
      herbal medicine, acupuncture, moxibustion, cupping, qigong, and Tai Chi. However,
      due to the poor quality of primary studies, clinical evidence is still weak. The
      potential benefits and safety of CM for hypertension still need to be confirmed
      in the future with well-designed RCTs of more persuasive primary endpoints and
      high-quality SRs. Evidence-based Chinese medicine for hypertension still has a
      long way to go. 

PMID- 23861721
TI  - Particle system based adaptive sampling on spherical parameter space to improve
      the MDL method for construction of statistical shape models.
AB  - Minimum description length (MDL) based group-wise registration was a state-of-the
      art method to determine the corresponding points of 3D shapes for the
      construction of statistical shape models (SSMs). However, it suffered from the
      problem that determined corresponding points did not uniformly spread on original
      shapes, since corresponding points were obtained by uniformly sampling the
      aligned shape on the parameterized space of unit sphere. We proposed a particle
      system based method to obtain adaptive sampling positions on the unit sphere to
      resolve this problem. Here, a set of particles was placed on the unit sphere to
      construct a particle system whose energy was related to the distortions of
      parameterized meshes. By minimizing this energy, each particle was moved on the
      unit sphere. When the system became steady, particles were treated as vertices to
      build a spherical mesh, which was then relaxed to slightly adjust vertices to
      obtain optimal sampling-positions. We used 47 cases of (left and right) lungs and
      50 cases of livers, (left and right) kidneys, and spleens for evaluations.
      Experiments showed that the proposed method was able to resolve the problem of
      the original MDL method, and the proposed method performed better in the
      generalization and specificity tests. 

PMID- 23861722
TI  - Comparative evaluation of osseointegrated dental implants based on platform
      switching concept: influence of diameter, length, thread shape, and in-bone
      positioning depth on stress-based performance.
AB  - This study aimed to investigate the influence of implant design (in terms of
      diameter, length, and thread shape), in-bone positioning depth, and bone
      posthealing crestal morphology on load transfer mechanisms of osseointegrated
      dental implants based on platform-switching concept. In order to perform an
      effective multiparametric comparative analysis, 11 implants different in
      dimensions and in thread features were analyzed by a linearly elastic 3
      dimensional finite element approach, under a static load. Implant models were
      integrated with the detailed model of a maxillary premolar bone segment.
      Different implant in-bone positioning levels were modeled, considering also
      different posthealing crestal bone morphologies. Bone overloading risk was
      quantified by introducing proper local stress measures, highlighting that implant
      diameter is a more effective design parameter than the implant length, as well as
      that thread shape and thread details can significantly affect stresses at peri
      implant bone, especially for short implants. Numerical simulations revealed that
      the optimal in-bone positioning depth results from the balance of 2 counteracting
      effects: cratering phenomena and bone apposition induced by platform-switching
      configuration. Proposed results contribute to identify the mutual influence of a
      number of factors affecting the bone-implant loading transfer mechanisms,
      furnishing useful insights and indications for choosing and/or designing threaded
      osseointegrated implants. 

PMID- 23861723
TI  - Effect of Pilates training on alpha rhythm.
AB  - In this study, the effect of Pilates training on the brain function was
      investigated through five case studies. Alpha rhythm changes during the Pilates
      training over the different regions and the whole brain were mainly analyzed,
      including power spectral density and global synchronization index (GSI). It was
      found that the neural network of the brain was more active, and the
      synchronization strength reduced in the frontal and temporal regions due to the
      Pilates training. These results supported that the Pilates training is very
      beneficial for improving brain function or intelligence. These findings maybe
      give us some line evidence to suggest that the Pilates training is very helpful
      for the intervention of brain degenerative diseases and cogitative dysfunction
      rehabilitation. 

PMID- 23861724
TI  - Segmentation of the striatum from MR brain images to calculate the 99mTc-TRODAT-1
      binding ratio in SPECT images.
AB  - Quantification of regional (99m)Tc-TRODAT-1 binding ratio in the striatum regions
      in SPECT images is essential for differential diagnosis between Alzheimer's and
      Parkinson's diseases. Defining the region of the striatum in the SPECT image is
      the first step toward success in the quantification of the TRODAT-1 binding
      ratio. However, because SPECT images reveal insufficient information regarding
      the anatomical structure of the brain, correct delineation of the striatum
      directly from the SPECT image is almost impossible. We present a method
      integrating the active contour model and the hybrid registration technique to
      extract regions from MR T1-weighted images and map them into the corresponding
      SPECT images. Results from three normal subjects suggest that the segmentation
      accuracy using the proposed method was compatible with the expert decision but
      has a higher efficiency and reproducibility than manual delineation. The binding
      ratio derived by this method correlated well (R (2) = 0.76) with those values
      calculated by commercial software, suggesting the feasibility of the proposed
      method. 

PMID- 23861725
TI  - Implementation of predictive data mining techniques for identifying risk factors
      of early AVF failure in hemodialysis patients.
AB  - Arteriovenous fistula (AVF) is an important vascular access for hemodialysis (HD)
      treatment but has 20-60% rate of early failure. Detecting association between
      patient's parameters and early AVF failure is important for reducing its
      prevalence and relevant costs. Also predicting incidence of this complication in
      new patients is a beneficial controlling procedure. Patient safety and
      preservation of early AVF failure is the ultimate goal. Our research society is
      Hasheminejad Kidney Center (HKC) of Tehran, which is one of Iran's largest renal
      hospitals. We analyzed data of 193 HD patients using supervised techniques of
      data mining approach. There were 137 male (70.98%) and 56 female (29.02%)
      patients introduced into this study. The average of age for all the patients was
      53.87 +/- 17.47 years. Twenty eight patients had smoked and the number of
      diabetic patients and nondiabetics was 87 and 106, respectively. A significant
      relationship was found between "diabetes mellitus," "smoking," and "hypertension"
      with early AVF failure in this study. We have found that these mentioned risk
      factors have important roles in outcome of vascular surgery, versus other
      parameters such as "age." Then we predicted this complication in future AVF
      surgeries and evaluated our designed prediction methods with accuracy rates of
      61.66%-75.13%. 

PMID- 23861726
TI  - An expert system based on Fisher score and LS-SVM for cardiac arrhythmia
      diagnosis.
AB  - An expert system having two stages is proposed for cardiac arrhythmia diagnosis.
      In the first stage, Fisher score is used for feature selection to reduce the
      feature space dimension of a data set. The second stage is classification stage
      in which least squares support vector machines classifier is performed by using
      the feature subset selected in the first stage to diagnose cardiac arrhythmia.
      Performance of the proposed expert system is evaluated by using an arrhythmia
      data set which is taken from UCI machine learning repository. 

PMID- 23861727
TI  - Epitope mapping of metuximab on CD147 using phage display and molecular docking.
AB  - Metuximab is the generic name of Licartin, a new drug for radioimmunotherapy of
      hepatocellular carcinoma. Although it is known to be a mouse monoclonal antibody
      against CD147, the complete epitope mediating the binding of metuximab to CD147
      remains unknown. We panned the Ph.D.-12 phage display peptide library against
      metuximab and got six mimotopes. The following bioinformatics analysis based on
      mimotopes suggested that metuximab recognizes a conformational epitope composed
      of more than 20 residues. The residues of its epitope may include T28, V30, K36,
      L38, K57, F74, D77, S78, D79, D80, Q81, G83, S86, N98, Q100, L101, H102, G103,
      P104, V131, P132, and K191. The homology modeling of metuximab and the docking of
      CD147 to metuximab were also performed. Based on the top one docking model, the
      epitope was predicted to contain 28 residues: AGTVFTTV (23-30), I37, D45, E84,
      V88, EPMGTANIQLH (92-102), VPP (131-133), Q164, and K191. Almost half of the
      residues predicted on the basis of mimotope analysis also appear in the docking
      result, indicating that both results are reliable. As the predicted epitopes of
      metuximab largely overlap with interfaces of CD147-CD147 interactions, a
      structural mechanism of metuximab is proposed as blocking the formation of CD147
      dimer. 

PMID- 23861728
TI  - Highlights from the Third International Central Nervous System Germ Cell Tumour
      symposium: laying the foundations for future consensus.
AB  - The Third International Central Nervous System (CNS) Germ Cell Tumour (GCT)
      Symposium brought together over 100 delegates from all over the world to learn
      about the latest developments in these tumours and discuss future strategies for
      their management. Some areas of consensus were agreed upon, and controversies
      were discussed. Among these, the classification of GCTs and the surgical approach
      to their management were among the greatest areas of difference between different
      parts of the world. The need for radiotherapy (RT) as a part of standard first
      line management for all malignant CNS GCTs was agreed, as well as the need for
      additional chemotherapy to maximise the cure in nongerminomatous malignant GCTs;
      the benefit of the addition of chemotherapy in localised germinoma to reduce the
      RT burden was also accepted as a good practice. The potential of biological
      parameters to assist the future diagnosis, treatment stratification, and disease
      monitoring for CNS GCTs was discussed. Such biological parameters may also
      represent targets for the development of novel therapies. The need for further
      collaboration between groups engaged in biological studies was agreed. The merits
      of proton beam RT were debated, and the importance of mitigating the long-term
      side effects of the treatment was underlined by a session on late effects. 

PMID- 23861729
TI  - Nematode-derived proteins suppress proliferation and cytokine production of
      antigen-specific T cells via induction of cell death.
AB  - In order to establish long-lasting infections in their mammalian host, filarial
      nematodes have developed sophisticated strategies to dampen their host's immune
      response. Proteins that are actively secreted by the parasites have been shown to
      induce the expansion of regulatory T cells and to directly interfere with
      effector T cell function. Here, we analyze the suppressive capacity of
      Onchocercavolvulus-derived excreted/secreted proteins. Addition of two
      recombinant O. volvulus proteins, abundant larval transcript-2 (OvALT-2) and
      novel larval transcript-1 (OvNLT-1) to cell cultures of T cell receptor
      transgenic CD4(+) and CD8(+) T cells suppressed antigen-specific stimulation in
      vitro. Ovalbumin-specific CD4(+) DO11.10 and OT-II T cells that had been
      stimulated with their cognate antigen in the presence of OvALT-2 or OvNLT-1
      displayed reduced DNA synthesis quantified by (3)H-thymidine incorporation and
      reduced cell division quantified by CFSE dilution. Furthermore, the IL-2 and IFN
      gamma response of ovalbumin-specific CD8(+) OT-I T cells was suppressed by OvALT
      2 and OvNLT-1. In contrast, another recombinant O. volvulus protein,
      microfilariae surface-associated antigen (Ov103), did not modulate T cell
      activation, thus serving as internal control for non-ESP-mediated artifacts.
      Suppressive capacity of the identified ESP was associated with induction of
      apoptosis in T cells demonstrated by increased exposure of phosphatidylserine on
      the plasma membrane. Of note, the digestion of recombinant proteins with
      proteinase K did not abolish the suppression of antigen-specific proliferation
      although the suppressive capacity of the identified excreted/secreted products
      was not mediated by low molecular weight contaminants in the undigested
      preparations. In summary, we identified two suppressive excreted/secreted
      products from O. volvulus, which interfere with the function of antigen-specific
      T cells in vitro. 

PMID- 23861731
TI  - A liver-specific defect of Acyl-CoA degradation produces hyperammonemia,
      hypoglycemia and a distinct hepatic Acyl-CoA pattern.
AB  - Most conditions detected by expanded newborn screening result from deficiency of
      one of the enzymes that degrade acyl-coenzyme A (CoA) esters in mitochondria. The
      role of acyl-CoAs in the pathophysiology of these disorders is poorly understood,
      in part because CoA esters are intracellular and samples are not generally
      available from human patients. We created a mouse model of one such condition,
      deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase (HL), in liver (HLLKO mice).
      HL catalyses a reaction of ketone body synthesis and of leucine degradation.
      Chronic HL deficiency and acute crises each produced distinct abnormal liver acyl
      CoA patterns, which would not be predictable from levels of urine organic acids
      and plasma acylcarnitines. In HLLKO hepatocytes, ketogenesis was undetectable.
      Carboxylation of [2-(14)C] pyruvate diminished following incubation of HLLKO
      hepatocytes with the leucine metabolite 2-ketoisocaproate (KIC). HLLKO mice also
      had suppression of the normal hyperglycemic response to a systemic pyruvate load,
      a measure of gluconeogenesis. Hyperammonemia and hypoglycemia, cardinal features
      of many inborn errors of acyl-CoA metabolism, occurred spontaneously in some
      HLLKO mice and were inducible by administering KIC. KIC loading also increased
      levels of several leucine-related acyl-CoAs and reduced acetyl-CoA levels.
      Ultrastructurally, hepatocyte mitochondria of KIC-treated HLLKO mice show marked
      swelling. KIC-induced hyperammonemia improved following administration of
      carglumate (N-carbamyl-L-glutamic acid), which substitutes for the product of an
      acetyl-CoA-dependent reaction essential for urea cycle function, demonstrating an
      acyl-CoA-related mechanism for this complication. 

PMID- 23861732
TI  - Host-parasite incongruences in rodent Eimeria suggest significant role of
      adaptation rather than cophylogeny in maintenance of host specificity.
AB  - The degree of host specificity, its phylogenetic conservativeness and origin are
      virtually unknown in Eimeria. This situation is largely due to the inadequate
      sample of eimerian molecular data available for reliable phylogenetic analyses.
      In this study, we extend the data set by adding 71 new sequences of coccidia
      infecting 16 small-mammal genera, mostly rodents. According to the respective
      feasibility of PCR gene amplification, the new samples are represented by one or
      more of the following genes: nuclear 18S rRNA, plastid ORF 470, and mitochondrial
      COI. Phylogenetic analyses of these sequences confirm the previous hypothesis
      that Eimeria, in its current morphology-based delimitation, is not a monophyletic
      group. Several samples of coccidia corresponding morphologically to other genera
      are scattered among the Eimeria lineages. More importantly, the distribution of
      eimerians from different hosts indicates that the clustering of eimerian species
      is influenced by their host specificity, but does not arise from a
      cophylogenetic/cospeciation process; while several clusters are specific to a
      particular host group, inner topologies within these clusters do not reflect host
      phylogeny. This observation suggests that the host specificity of Eimeria is
      caused by adaptive rather than cophylogenetic processes. 

PMID- 23861733
TI  - Live imaging of whole mouse embryos during gastrulation: migration analyses of
      epiblast and mesodermal cells.
AB  - During gastrulation in the mouse embryo, dynamic cell movements including
      epiblast invagination and mesodermal layer expansion lead to the establishment of
      the three-layered body plan. The precise details of these movements, however, are
      sometimes elusive, because of the limitations in live imaging. To overcome this
      problem, we developed techniques to enable observation of living mouse embryos
      with digital scanned light sheet microscope (DSLM). The achieved deep and high
      time-resolution images of GFP-expressing nuclei and following 3D tracking
      analysis revealed the following findings: (i) Interkinetic nuclear migration
      (INM) occurs in the epiblast at embryonic day (E)6 and 6.5. (ii) INM-like
      migration occurs in the E5.5 embryo, when the epiblast is a monolayer and not yet
      pseudostratified. (iii) Primary driving force for INM at E6.5 is not pressure
      from neighboring nuclei. (iv) Mesodermal cells migrate not as a sheet but as
      individual cells without coordination. 

PMID- 23861734
TI  - Physical proximity may promote lateral acquisition of bacterial symbionts in
      vesicomyid clams.
AB  - Vesicomyid clams harbor intracellular sulfur-oxidizing bacteria that are
      predominantly maternally inherited and co-speciate with their hosts. Genome
      recombination and the occurrence of non-parental strains were recently
      demonstrated in symbionts. However, mechanisms favoring such events remain to be
      identified. In this study, we investigated symbionts in two phylogenetically
      distant vesicomyid species, Christineconcha regab and Laubiericoncha chuni, which
      sometimes co-occur at a cold-seep site in the Gulf of Guinea. We showed that each
      of the two species harbored a single dominant bacterial symbiont strain. However,
      for both vesicomyid species, the symbiont from the other species was occasionally
      detected in the gills using fluorescence in situ hybridization and gene sequences
      analyses based on six symbiont marker genes. Symbiont strains co-occurred within
      a single host only at sites where both host species were found; whereas one
      single symbiont strain was detected in C. regab specimens from a site where no L.
      chuni individuals had been observed. These results suggest that physical
      proximity favored the acquisition of non-parental symbiont strains in
      Vesicomyidae. Over evolutionary time, this could potentially lead to genetic
      exchanges among symbiont species and eventually symbiont displacement. Symbiont
      densities estimated using 3D fluorescence in situ hybridization varied among host
      species and sites, suggesting flexibility in the association despite the fact
      that a similar type of metabolism is expected in all symbionts. 

PMID- 23861735
TI  - Processing irrelevant location information: practice and transfer effects in a
      Simon task.
AB  - How humans produce cognitively driven fine motor movements is a question of
      fundamental importance in how we interact with the world around us. For example,
      we are exposed to a constant stream of information and we must select the
      information that is most relevant by which to guide our actions. In the present
      study, we employed a well-known behavioral assay called the Simon task to better
      understand how humans are able to learn to filter out irrelevant information. We
      trained subjects for four days with a visual stimulus presented, alternately, in
      central and lateral locations. Subjects responded with one hand moving a joystick
      in either the left or right direction. They were instructed to ignore the
      irrelevant location information and respond based on color (e.g. red to the right
      and green to the left). On the fifth day, an additional testing session was
      conducted where the task changed and the subjects had to respond by shape (e.g.
      triangle to the right and rectangle to the left). They were instructed to ignore
      the color and location, and respond based solely on the task relevant shape. We
      found that the magnitude of the Simon effect decreases with training, however it
      returns in the first few trials after a break. Furthermore, task-defined
      associations between response direction and color did not significantly affect
      the Simon effect based on shape, and no significant associative learning from the
      specific stimulus-response features was found for the centrally located stimuli.
      We discuss how these results are consistent with a model involving route
      suppression/gating of the irrelevant location information. Much of the learning
      seems to be driven by subjects learning to suppress irrelevant location
      information, however, this seems to be an active inhibition process that requires
      a few trials of experience to engage. 

PMID- 23861736
TI  - Subspace identification and classification of healthy human gait.
AB  - PURPOSE: The classification between different gait patterns is a frequent task in
      gait assessment. The base vectors were usually found using principal component
      analysis (PCA) is replaced by an iterative application of the support vector
      machine (SVM). The aim was to use classifyability instead of variability to build
      a subspace (SVM space) that contains the information about classifiable aspects
      of a movement. The first discriminant of the SVM space will be compared to a
      discriminant found by an independent component analysis (ICA) in the SVM space.
      METHODS: Eleven runners ran using shoes with different midsoles. Kinematic data,
      representing the movements during stance phase when wearing the two shoes, was
      used as input to a PCA and SVM. The data space was decomposed by an iterative
      application of the SVM into orthogonal discriminants that were able to classify
      the two movements. The orthogonal discriminants spanned a subspace, the SVM
      space. It represents the part of the movement that allowed classifying the two
      conditions. The data in the SVM space was reconstructed for a visual assessment
      of the movement difference. An ICA was applied to the data in the SVM space to
      obtain a single discriminant. Cohen's d effect size was used to rank the PCA
      vectors that could be used to classify the data, the first SVM discriminant or
      the ICA discriminant. RESULTS: The SVM base contains all the information that
      discriminates the movement of the two shod conditions. It was shown that the SVM
      base contains some redundancy and a single ICA discriminant was found by applying
      an ICA in the SVM space. CONCLUSIONS: A combination of PCA, SVM and ICA is best
      suited to extract all parts of the gait pattern that discriminates between the
      two movements and to find a discriminant for the classification of dichotomous
      kinematic data.

PMID- 23861737
TI  - A unified framework for association analysis with multiple related phenotypes.
AB  - We consider the problem of assessing associations between multiple related
      outcome variables, and a single explanatory variable of interest. This problem
      arises in many settings, including genetic association studies, where the
      explanatory variable is genotype at a genetic variant. We outline a framework for
      conducting this type of analysis, based on Bayesian model comparison and model
      averaging for multivariate regressions. This framework unifies several common
      approaches to this problem, and includes both standard univariate and standard
      multivariate association tests as special cases. The framework also unifies the
      problems of testing for associations and explaining associations - that is,
      identifying which outcome variables are associated with genotype. This provides
      an alternative to the usual, but conceptually unsatisfying, approach of resorting
      to univariate tests when explaining and interpreting significant multivariate
      findings. The method is computationally tractable genome-wide for modest numbers
      of phenotypes (e.g. 5-10), and can be applied to summary data, without access to
      raw genotype and phenotype data. We illustrate the methods on both simulated
      examples, and to a genome-wide association study of blood lipid traits where we
      identify 18 potential novel genetic associations that were not identified by
      univariate analyses of the same data. 

PMID- 23861738
TI  - A new method for the detection of neutralizing antibodies against mumps virus.
AB  - Neutralization test is the most reliable method of evaluating immunity against
      viral diseases but there is no standard procedure for mumps virus, with tests
      differing in the infectivity of the challenge virus, 50% plaque reduction or
      complete inhibition of cytopathic effects (CPE), and usage of complement. A
      reliable, easy, and simple neutralization test for mumps virus was developed in
      this study. A recombinant mumps virus expressing GFP was generated as a challenge
      virus. Complement was added to the neutralizing mixture at 1?200 when stocked
      serum samples were used. Neutralizing antibody titers were expressed as the
      reciprocal of the highest dilution that did not exceed two-fold of FU values (GFP
      expression) of the cell control wells. A total of 1,452 serum samples were
      assayed by inhibition of GFP expression in comparison with those examined by
      conventional 100% inhibition of CPE. 1,367 (94.1%) showed similar neutralizing
      antibody titers when examined by both methods. The GFP expression inhibition
      assay, using a recombinant mumps virus expressing GFP, is a simple and time-
      saving method. 

PMID- 23861740
TI  - Patterns of risk of cancer in patients with metal-on-metal hip replacements
      versus other bearing surface types: a record linkage study between a prospective
      joint registry and general practice electronic health records in England.
AB  - BACKGROUND: There are concerns that metal-on-metal hip implants may cause cancer.
      The objective of this study was to evaluate patterns and timing of risk of cancer
      in patients with metal-on-metal total hip replacements (THR). METHODS: In a
      linkage study between the English National Joint Registry (NJR) and the Clinical
      Practice Research Datalink (CPRD), we selected all THR surgeries (NJR) between
      2003 and 2010 (n = 11,540). THR patients were stratified by type of bearing
      surface. Patients were followed up for cancer and Poisson regression was used to
      derive adjusted relative rates (RR). RESULTS: The risk of cancer was similar in
      patients with hip resurfacing (RR 0.69; 95% Confidence Interval [CI] 0.39-1.22)
      or other types of bearing surfaces (RR 0.96; 95% CI 0.64-1.43) compared to
      individuals with stemmed metal-on-metal THR. The pattern of cancer risk over time
      did not support a detrimental effect of metal hip implants. There was substantial
      confounding: patients with metal-on-metal THRs used fewer drugs and had less
      comorbidity. CONCLUSIONS: Metal-on-metal THRs were not associated with an
      increased risk of cancer. There were substantial baseline differences between the
      different hip implants, indicating possibility of confounding in the comparisons
      between different types of THR implants.

PMID- 23861741
TI  - Global transcriptomic analysis of human neuroblastoma cells in response to
      enterovirus type 71 infection.
AB  - Human enterovirus type 71 (EV71) is the major pathogen of hand-foot-and-mouth
      disease (HFMD) and has been associated with severe neurological disease and even
      death in infants and young children. The pathogenesis of EV71 infection in the
      human central nervous system remains unclear. In this study, human whole genome
      microarray was employed to perform transcriptome profiling in SH-SY5Y human
      neuroblastoma cells infected with EV71. The results indicated that EV71 infection
      lead to altered expression of 161 human mRNAs, including 74 up-regulated genes
      and 87 down-regulated genes. Bioinformatics analysis indicated the possible roles
      of the differentially regulated mRNAs in selected pathways, including cell
      cycle/proliferation, apoptosis, and cytokine/chemokine responses. Finally, the
      microarray results were validated using real-time RT-PCR with high identity.
      Overall, our results provided fundamental information regarding the host response
      to EV71 infection in human neuroblastoma cells, and this finding will help
      explain the pathogenesis of EV71 infection and virus-host interaction. 

PMID- 23861742
TI  - Molecular analysis of non-specific protection against murine malaria induced by
      BCG vaccination.
AB  - Although the effectiveness of BCG vaccination in preventing adult pulmonary
      tuberculosis (TB) has been highly variable, epidemiologic studies have suggested
      that BCG provides other general health benefits to vaccinees including reducing
      the impact of asthma, leprosy, and possibly malaria. To further evaluate whether
      BCG immunization protects against malarial parasitemia and to define molecular
      correlates of this non-specific immunity, mice were vaccinated with BCG and then
      challenged 2 months later with asexual blood stage Plasmodium yoelii 17XNL (PyNL)
      parasites. Following challenge with PyNL, significant decreases in parasitemia
      were observed in BCG vaccinated mice relative to naive controls. To identify
      immune molecules that may be associated with the BCG-induced protection, gene
      expression was evaluated by RT-PCR in i) naive controls, ii) BCG-vaccinated mice,
      iii) PyNL infected mice and iv) BCG vaccinated/PyNL infected mice at 0, 1, 5, and
      9 days after the P. yoelii infection. The expression results showed that i) BCG
      immunization induces the expression of at least 18 genes including the anti
      microbial molecules lactoferrin, eosinophil peroxidase, eosinophil major basic
      protein and the cathelicidin-related antimicrobial peptide (CRAMP); ii) an active
      PyNL infection suppresses the expression of important immune response molecules;
      and iii) the extent of PyNL-induced suppression of specific genes is reduced in
      BCG-vaccinated/PyNL infected mice. To validate the gene expression data, we
      demonstrated that pre-treatment of malaria parasites with lactoferrin or the
      cathelicidin LL-37 peptide decreases the level of PyNL parasitemias in mice.
      Overall, our study suggests that BCG vaccination induces the expression of non
      specific immune molecules including antimicrobial peptides which may provide an
      overall benefit to vaccinees by limiting infections of unrelated pathogens such
      as Plasmodium parasites. 

PMID- 23861743
TI  - A DNA-based registry for all animal species: the barcode index number (BIN)
      system.
AB  - Because many animal species are undescribed, and because the identification of
      known species is often difficult, interim taxonomic nomenclature has often been
      used in biodiversity analysis. By assigning individuals to presumptive species,
      called operational taxonomic units (OTUs), these systems speed investigations
      into the patterning of biodiversity and enable studies that would otherwise be
      impossible. Although OTUs have conventionally been separated through their
      morphological divergence, DNA-based delineations are not only feasible, but have
      important advantages. OTU designation can be automated, data can be readily
      archived, and results can be easily compared among investigations. This study
      exploits these attributes to develop a persistent, species-level taxonomic
      registry for the animal kingdom based on the analysis of patterns of nucleotide
      variation in the barcode region of the cytochrome c oxidase I (COI) gene. It
      begins by examining the correspondence between groups of specimens identified to
      a species through prior taxonomic work and those inferred from the analysis of
      COI sequence variation using one new (RESL) and four established (ABGD, CROP,
      GMYC, jMOTU) algorithms. It subsequently describes the implementation, and
      structural attributes of the Barcode Index Number (BIN) system. Aside from a
      pragmatic role in biodiversity assessments, BINs will aid revisionary taxonomy by
      flagging possible cases of synonymy, and by collating geographical information,
      descriptive metadata, and images for specimens that are likely to belong to the
      same species, even if it is undescribed. More than 274,000 BIN web pages are now
      available, creating a biodiversity resource that is positioned for rapid growth. 

PMID- 23861744
TI  - Modes of action of ADP-ribosylated elongation factor 2 in inhibiting the
      polypeptide elongation cycle: a modeling study.
AB  - Despite the fact that ADP-ribosylation of eukaryotic elongation factor 2 (EF2)
      leads to inhibition of protein synthesis, the mechanism by which ADP-ribosylated
      EF2 (ADPR*EF2) causes this inhibition remains controversial. Here, we applied
      modeling approaches to investigate the consequences of various modes of ADPR*EF2
      inhibitory actions on the two coupled processes, the polypeptide chain elongation
      and ADP-ribosylation of EF2. Modeling of experimental data indicates that
      ADPR*EF2 fully blocks the late-phase translocation of tRNAs; but the impairment
      in the translocation upstream process, mainly the GTP-dependent factor binding
      with the pretranslocation ribosome and/or the guanine nucleotide exchange in EF2,
      is responsible for the overall inhibition kinetics. The reduced ADPR*EF2-ribosome
      association spares the ribosome to bind and shield native EF2 against toxin
      attack, thereby deferring the inhibition of protein synthesis inhibition and
      inactivation of EF2. Minimum association with the ribosome also keeps ADPR*EF2 in
      an accessible state for toxins to catalyze the reverse reaction when nicotinamide
      becomes available. Our work underscores the importance of unveiling the
      interactions between ADPR*EF2 and the ribosome, and argues against that toxins
      inhibit protein synthesis through converting native EF2 to a competitive
      inhibitor to actively disable the ribosome. 

PMID- 23861745
TI  - Characterization of DNA binding property of the HIV-1 host factor and tumor
      suppressor protein Integrase Interactor 1 (INI1/hSNF5).
AB  - Integrase Interactor 1 (INI1/hSNF5) is a component of the hSWI/SNF chromatin
      remodeling complex. The INI1 gene is either deleted or mutated in rhabdoid
      cancers like ATRT (Atypical terratoid and rhabdoid tumor). INI1 is also a host
      factor for HIV-1 replication. INI1 binds DNA non-specifically. However, the
      mechanism of DNA binding and its biological role are unknown. From agarose gel
      retardation assay (AGRA), Ni-NTA pull-down and atomic force microscopy (AFM)
      studies we show that amino acids 105-183 of INI1 comprise the minimal DNA binding
      domain (DBD). The INI1 DBD is absent in plants and in yeast SNF5. It is present
      in Caenorhabditis elegans SNF5, Drosophila melanogaster homologue SNR1 and is a
      highly conserved domain in vertebrates. The DNA binding property of this domain
      in SNR1, that is only 58% identical to INI1/hSNF5, is conserved. Analytical
      ultracentrifugation studies of INI1 DBD and INI1 DBD:DNA complexes at different
      concentrations show that the DBD exists as a monomer at low protein concentration
      and two molecules of monomer binds one molecule of DNA. At high protein
      concentration, it exists as a dimer and binds two DNA molecules. Furthermore,
      isothermal calorimetry (ITC) experiments demonstrate that the DBD monomer binds
      DNA with a stoichiometry (N) of ~0.5 and Kd  = 0.94 uM whereas the DBD dimer
      binds two DNA molecules sequentially with K'd1 = 222 uM and K'd2 = 1.16 uM.
      Monomeric DBD binding to DNA is enthalpy driven (DeltaH = -29.9 KJ/mole). Dimeric
      DBD binding to DNA is sequential with the first binding event driven by positive
      entropy (DeltaH'1 = 115.7 KJ/mole, TDeltaS'1 = 136.8 KJ/mole) and the second
      binding event driven by negative enthalpy (DeltaH'2 = -106.3 KJ/mole, TDeltaS'2 =
      -75.7 KJ/mole). Our model for INI1 DBD binding to DNA provides new insights into
      the mechanism of DNA binding by INI1. 

PMID- 23861746
TI  - Enpp1: a potential facilitator of breast cancer bone metastasis.
AB  - Bone is the most common site of breast cancer metastasis and once established, it
      is frequently incurable. Critical to our ability to prevent and treat bone
      metastasis is the identification of the key factors mediating its establishment
      and understanding their biological function. To address this issue we previously
      carried out an in vivo selection process to isolate murine mammary tumor sublines
      possessing an enhanced ability to colonize the bone. A comparison of gene
      expression between parental cells and sublines by genome-wide cDNA microarray
      analysis revealed several potential mediators of bone metastasis, including the
      pyrophosphate-generating ectoenzyme Enpp1. By qRT-PCR and Western analysis we
      found that expression of Enpp1 was elevated in human breast cancer cell lines
      known to produce bone metastasis in animal models compared to non-metastatic and
      normal mammary epithelial cell lines. Further, in clinical specimens, levels of
      Enpp1 were significantly elevated in human primary breast tumors relative to
      normal mammary epithelium, with highest levels observed in breast-bone metastasis
      as determined by qRT-PCR and immunohistochemical analysis. To examine the
      potential role of Enpp1 in the development of bone metastasis, Enpp1 expression
      was stably increased in the breast cancer cell line MDA-MB-231 and the ability to
      colonize the bone following intracardiac and direct intratibial injection of
      athymic nude mice was determined. By both routes of administration, increased
      expression of Enpp1 enhanced the ability of MDA-MB-231 cells to form tumors in
      the bone relative to cells expressing vector alone, as determined by digital
      radiography and histological analysis. Taken together, these data suggest a
      potential role for Enpp1 in the development of breast cancer bone metastasis. 

PMID- 23861739
TI  - Fine-scale patterns of population stratification confound rare variant
      association tests.
AB  - Advances in next-generation sequencing technology have enabled systematic
      exploration of the contribution of rare variation to Mendelian and complex
      diseases. Although it is well known that population stratification can generate
      spurious associations with common alleles, its impact on rare variant association
      methods remains poorly understood. Here, we performed exhaustive coalescent
      simulations with demographic parameters calibrated from exome sequence data to
      evaluate the performance of nine rare variant association methods in the presence
      of fine-scale population structure. We find that all methods have an inflated
      spurious association rate for parameter values that are consistent with levels of
      differentiation typical of European populations. For example, at a nominal
      significance level of 5%, some test statistics have a spurious association rate
      as high as 40%. Finally, we empirically assess the impact of population
      stratification in a large data set of 4,298 European American exomes. Our results
      have important implications for the design, analysis, and interpretation of rare
      variant genome-wide association studies. 

PMID- 23861747
TI  - Prospective validation of candidate SNPs of VEGF/VEGFR pathway in metastatic
      colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab.
AB  - PURPOSE: The potential impact of different SNPs of VEGF/VEGFR pathway on the
      clinical outcome of mCRC patients receiving bev-containing regimens has been
      investigated in retrospective experiences with contrasting results. We previously
      reported the association of VEGFA rs833061 C/T variants with PFS in metastatic
      colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab. The
      primary objective of this work was to prospectively validate that retrospective
      finding. A confirmatory analysis of other SNPs of VEGF/VEGFR pathway genes was
      included. EXPERIMENTAL DESIGN: To detect a HR for PFS of 1.7 for VEGFA rs833061
      T/T compared to C- variants in metastatic colorectal cancer patients treated with
      first-line FOLFIRI plus bevacizumab, setting two-sided alpha = 0.05 and beta =
      0.20, 199 events were required. VEGFA rs699946 A/G, rs699947 A/C, VEGFR1
      rs9582036 A/C and rs7993418 A/G, VEGFR2 rs11133360 C/T, rs12505758 C/T and
      rs2305948 C/T and EPAS1 rs4145836 A/G were also tested. Germ-line DNA was
      extracted from peripheral blood. SNPs were analyzed by PCR and sequencing.
      RESULTS: Four-hundred-twenty-four pts were included. At the univariate analysis,
      no differences according to VEGFA rs833061 C/T variants were observed in PFS (p =
      0.38) or OS (p = 0.95). Among analyzed SNPs, only VEGFR2 rs12505758 C- variants,
      compared to T/T, were associated to shorter PFS (HR: 1.36 [1.05-1.75], p = 0.015,
      dominant genetic model) and OS, with a trend toward significance (HR: 1.34 [0.95
      1.88], p = 0.088). In the multivariate model, this association retained
      significance (HR: 1.405 [1.082-1.825], p = 0.012) in PFS, that was lost by
      applying multiple testing correction (p = 0.14). CONCLUSION: This prospective
      experience failed to validate the hypothesized predictive impact of VEGFA
      rs833061 variants. Retrospective findings on different candidate SNPs were not
      confirmed. Only VEGFR2 rs12505758 variants, whose prognostic and not predictive
      impact was previously reported, correlated with PFS. Given the complexity of
      angiogenesis, it is rather unlike that a single germ-line SNP might be a good
      predictor of benefit from bevacizumab.

PMID- 23861748
TI  - Screening for distress in routine oncological care-a survey in 520 melanoma
      patients.
AB  - INTRODUCTION: Despite the increasing incidence of melanoma little is known about
      patients' emotional distress associated with this disease. Supplemented by the
      problem list (PL), the distress thermometer (DT) is a recommended screening
      instrument to measure psychosocial distress in cancer patients. Our objective was
      to explore the acceptance and the feasibility of the DT and PL as a concise
      screening tool in an ambulatory setting for routine care and to elucidate
      determinants of distress in melanoma patients with regard to sociodemographic and
      clinical variables. METHODS: Consecutive melanoma outpatients were asked to
      complete the DT with the PL prior to their scheduled consultation. Demographic
      and clinical data were obtained from the patients' charts. Clinical data included
      melanoma stage, time since diagnosis, previous treatment, current treatment, and
      other cancer disease. RESULTS: Out of 734 patients recruited into the study, 520
      patients (71%) completed both the DT and the PL. Forty-seven percent met the >=5
      cut-off score for distress. Younger and employed patients reported higher
      distress than older and retired patients. A cut-off score of >=5 was closely
      associated with self-reported emotional sources of distress, with practical
      problems, especially at work, family problems (dealing with the partner), and
      physical problems like pain, appearance, getting around, and nausea. Apart from
      higher distress under current systemic treatment, no associations were found
      between distress and clinical data. CONCLUSION: The DT together with the PL seems
      to be an economically reasonable screening tool to measure psychosocial distress
      in melanoma patients. In particular, younger melanoma patients who are currently
      employed are prone to experience distress at some point after diagnosis, but
      there appears to be almost no association between clinical data and the extent of
      distress. To characterize the impact of distress on disease outcome and quality
      of life in melanoma patients, further research is needed.

PMID- 23861749
TI  - Systematic review of the empirical evidence of study publication bias and outcome
      reporting bias - an updated review.
AB  - BACKGROUND: The increased use of meta-analysis in systematic reviews of
      healthcare interventions has highlighted several types of bias that can arise
      during the completion of a randomised controlled trial. Study publication bias
      and outcome reporting bias have been recognised as a potential threat to the
      validity of meta-analysis and can make the readily available evidence unreliable
      for decision making. METHODOLOGY/PRINCIPAL FINDINGS: In this update, we review
      and summarise the evidence from cohort studies that have assessed study
      publication bias or outcome reporting bias in randomised controlled trials.
      Twenty studies were eligible of which four were newly identified in this update.
      Only two followed the cohort all the way through from protocol approval to
      information regarding publication of outcomes. Fifteen of the studies
      investigated study publication bias and five investigated outcome reporting bias.
      Three studies have found that statistically significant outcomes had a higher
      odds of being fully reported compared to non-significant outcomes (range of odds
      ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that
      40-62% of studies had at least one primary outcome that was changed, introduced,
      or omitted. We decided not to undertake meta-analysis due to the differences
      between studies. CONCLUSIONS: This update does not change the conclusions of the
      review in which 16 studies were included. Direct empirical evidence for the
      existence of study publication bias and outcome reporting bias is shown. There is
      strong evidence of an association between significant results and publication;
      studies that report positive or significant results are more likely to be
      published and outcomes that are statistically significant have higher odds of
      being fully reported. Publications have been found to be inconsistent with their
      protocols. Researchers need to be aware of the problems of both types of bias and
      efforts should be concentrated on improving the reporting of trials.

PMID- 23861750
TI  - Label free fragment screening using surface plasmon resonance as a tool for
      fragment finding - analyzing parkin, a difficult CNS target.
AB  - Surface Plasmon Resonance (SPR) is rarely used as a primary High-throughput
      Screening (HTS) tool in fragment-based approaches. With SPR instruments becoming
      increasingly high-throughput it is now possible to use SPR as a primary tool for
      fragment finding. SPR becomes, therefore, a valuable tool in the screening of
      difficult targets such as the ubiquitin E3 ligase Parkin. As a prerequisite for
      the screen, a large number of SPR tests were performed to characterize and
      validate the active form of Parkin. A set of compounds was designed and used to
      define optimal SPR assay conditions for this fragment screen. Using these
      conditions, more than 5000 pre-selected fragments from our in-house library were
      screened for binding to Parkin. Additionally, all fragments were simultaneously
      screened for binding to two off target proteins to exclude promiscuous binding
      compounds. A low hit rate was observed that is in line with hit rates usually
      obtained by other HTS screening assays. All hits were further tested in dose
      responses on the target protein by SPR for confirmation before channeling the
      hits into Nuclear Magnetic Resonance (NMR) and other hit-confirmation assays. 

PMID- 23861751
TI  - Regular moderate or intense exercise prevents depression-like behavior without
      change of hippocampal tryptophan content in chronically tryptophan-deficient and
      stressed mice.
AB  - Regular exercise has an antidepressant effect in human subjects. Studies using
      animals have suggested that the antidepressant effect of exercise is attributable
      to an increase of brain 5-hydroxytryptamine (5-HT); however, the precise
      mechanism underlying the antidepressant action via exercise is unclear. In
      contrast, the effect of 5-HT on antidepressant activity has not been clarified,
      in part because the therapeutic response to antidepressant drugs has a time lag
      in spite of the rapid increase of brain 5-HT upon administration of these drugs.
      This study was designed to investigate the contribution of brain 5-HT to the
      antidepressant effect of exercise. Mice were fed a tryptophan-deficient diet and
      stressed using chronic unpredictable stress (CUS) for 4 weeks with or without the
      performance of either moderate or intense exercise on a treadmill 3 days per
      week. The findings demonstrated that the onset of depression-like behavior is
      attributable not to chronic reduction of 5-HT but to chronic stress. Regular
      exercise, whether moderate or intense, prevents depression-like behavior with an
      improvement of adult hippocampal cell proliferation and survival and without the
      recovery of 5-HT. Concomitantly, the mice that exercised showed increased
      hippocampal noradrenaline. Regular exercise prevents the impairment of not long
      term memory but short-term memory in a 5-HT-reduced state. Together, these
      findings suggest that: (1) chronic reduction of brain 5-HT may not contribute to
      the onset of depression-like behavior; (2) regular exercise, whether moderate or
      intense, prevents the onset of chronic stress-induced depression-like behavior
      independent of brain 5-HT and dependent on brain adrenaline; and (3) regular
      exercise prevents chronic tryptophan reduction-induced impairment of not long
      term but short-term memory. 

PMID- 23861752
TI  - Costly advertising and the evolution of cooperation.
AB  - In this paper, I investigate the co-evolution of fast and slow strategy spread
      and game strategies in populations of spatially distributed agents engaged in a
      one off evolutionary dilemma game. Agents are characterized by a pair of traits,
      a game strategy (cooperate or defect) and a binary 'advertising' strategy
      (advertise or don't advertise). Advertising, which comes at a cost [Formula: see
      text], allows investment into faster propagation of the agents' traits to
      adjacent individuals. Importantly, game strategy and advertising strategy are
      subject to the same evolutionary mechanism. Via analytical reasoning and
      numerical simulations I demonstrate that a range of advertising costs exists,
      such that the prevalence of cooperation is significantly enhanced through co
      evolution. Linking costly replication to the success of cooperators exposes a
      novel co-evolutionary mechanism that might contribute towards a better
      understanding of the origins of cooperation-supporting heterogeneity in agent
      populations. 

PMID- 23861753
TI  - Cry1Ab treatment has no effects on viability of cultured porcine intestinal
      cells, but triggers Hsp70 expression.
AB  - In vitro testing can contribute to reduce the risk that the use of genetically
      modified (GM) crops and their proteins show unintended toxic effects. Here we
      introduce a porcine intestinal cell culture (IPEC-J2) as appropriate in vitro
      model and tested the possible toxic potential of Cry1Ab protein, commonly
      expressed in GM-maize. For comprehensive risk assessment we used WST-1 conversion
      and ATP content as metabolic markers for proliferation, lactate dehydrogenase
      release as indicator for cells with compromised membrane and transepithelial
      electrical resistance as parameter indicating membrane barrier function. The
      results were compared to the effects of valinomycin, a potassium ionophore, known
      to induce cytotoxic effects in most mammalian cell types. Whereas no toxicity was
      observed after Cry1Ab treatment, valinomycin induced a decrease in IPEC-J2
      viability. This was confirmed by dynamic monitoring of cellular responses.
      Additionally, two dimensional differential in-gel electrophoresis was performed.
      Only three proteins were differentially expressed. The functions of these
      proteins were associated with responses to stress. The up-regulation of heat
      shock protein Hsp70 was verified by Western blotting as well as by enzyme-linked
      immunosorbent assay and may be related to a protective function. These findings
      suggest that the combination of in vitro testing and proteomic analysis may serve
      as a promising tool for mechanism based safety assessment. 

PMID- 23861754
TI  - Transcriptional activation of c3 and hsp70 as part of the immune response of
      Acropora millepora to bacterial challenges.
AB  - The impact of disease outbreaks on coral physiology represents an increasing
      concern for the fitness and resilience of reef ecosystems. Predicting the
      tolerance of corals to disease relies on an understanding of the coral immune
      response to pathogenic interactions. This study explored the transcriptional
      response of two putative immune genes (c3 and c-type lectin) and one stress
      response gene (hsp70) in the reef building coral, Acropora millepora challenged
      for 48 hours with bacterial strains, Vibrio coralliilyticus and Alteromonas sp.
      at concentrations of 10(6) cells ml(-1). Coral fragments challenged with V.
      coralliilyticus appeared healthy while fragments challenged with Alteromonas sp.
      showed signs of tissue lesions after 48 hr. Coral-associated bacterial community
      profiles assessed using denaturing gradient gel electrophoresis changed after
      challenge by both bacterial strains with the Alteromonas sp. treatment
      demonstrating the greatest community shift. Transcriptional profiles of c3 and
      hsp70 increased at 24 hours and correlated with disease signs in the Alteromonas
      sp. treatment. The expression of hsp70 also showed a significant increase in V.
      coralliilyticus inoculated corals at 24 h suggesting that even in the absence of
      disease signs, the microbial inoculum activated a stress response in the coral. C
      type lectin did not show a response to any of the bacterial treatments. Increase
      in gene expression of c3 and hsp70 in corals showing signs of disease indicates
      their potential involvement in immune and stress response to microbial
      challenges. 

PMID- 23861755
TI  - The profile and treatment outcomes of the older (aged 60 years and above)
      tuberculosis patients in Tamilnadu, South India.
AB  - BACKGROUND: With changing demographic patterns in the context of a high
      tuberculosis (TB) burden country, like India, there is very little information on
      the clinical and demographic factors associated with poor treatment outcome in
      the sub-group of older TB patients. The study aimed to assess the proportion of
      older TB patients (60 years of age and more), to compare the type of TB and
      treatment outcomes between older TB patients and other TB patients (less than 60
      years of age) and to describe the demographic and clinical characteristics of
      older TB patients and assess any associations with TB treatment outcomes.
      METHODS: A retrospective cohort study involving a review of records from April to
      June 2011 in the 12 selected districts of Tamilnadu, India. Demographic, clinical
      and WHO defined disease classifications and treatment outcomes of all TB patients
      aged 60 years and above were extracted from TB registers maintained routinely by
      Revised National TB Control Program (RNTCP). RESULTS: Older TB patients accounted
      for 14% of all TB patients, of whom 47% were new sputum positive. They had 38%
      higher risk of unfavourable treatment outcomes as compared to all other TB
      patients (Relative risk (RR)-1.4, 95% CI 1.2-1.6). Among older TB patients, the
      risk for unfavourable treatment outcomes was higher for those aged 70 years and
      more (RR 1.5, 95% CI 1.2-1.9), males (RR 1.5, 95% CI 1.0-2.1), re-treatment
      patients (RR 2.5, 95% CI 1.9-3.2) and those who received community-based Direct
      Observed Treatment (RR 1.4, 95% CI 1.1-1.9). CONCLUSION: Treatment outcomes were
      poor in older TB patients warranting special attention to this group - including
      routine assessment and recording of co-morbidities, a dedicated recording,
      reporting and monitoring of outcomes for this age-group and collaboration with
      National programme of non-communicable diseases for comprehensive management of
      co-morbidities.

PMID- 23861757
TI  - Metabolic engineering of Escherichia coli for the production of xylonate.
AB  - Xylonate is a valuable chemical for versatile applications. Although the chemical
      synthesis route and microbial conversion pathway were established decades ago, no
      commercial production of xylonate has been obtained so far. In this study, the
      industrially important microorganism Escherichia coli was engineered to produce
      xylonate from xylose. Through the coexpression of a xylose dehydrogenase (xdh)
      and a xylonolactonase (xylC) from Caulobacter crescentus, the recombinant strain
      could convert 1 g/L xylose to 0.84 g/L xylonate and 0.10 g/L xylonolactone after
      being induced for 12 h. Furthermore, the competitive pathway for xylose
      catabolism in E. coli was blocked by disrupting two genes (xylA and xylB)
      encoding xylose isomerase and xylulose kinase. Under fed-batch conditions, the
      finally engineered strain produced up to 27.3 g/L xylonate and 1.7 g/L
      xylonolactone from 30 g/L xylose, about 88% of the theoretical yield. These
      results suggest that the engineered E. coli strain has a promising perspective
      for large-scale production of xylonate. 

PMID- 23861756
TI  - High risk sexual behaviors for HIV among the in-school youth in Swaziland: a
      structural equation modeling approach.
AB  - BACKGROUND: Global efforts in response to the increased prevalence of the human
      immunodeficiency virus (HIV) are mainly aimed at reducing high risk sexual
      behaviors among young people. However, knowledge regarding intentions of young
      people to engage in protective sexual behaviors is still lacking in many
      countries around the world, especially in Sub-Saharan Africa where prevalence of
      human immunodeficiency virus is the highest. The objective of this study was to
      test the theory of planned behavior (TPB) for predicting factors associated with
      protective sexual behaviors, including sexual abstinence and condom use, among in
      school youths aged between 15 and 19 years in Swaziland. METHODS: This cross
      sectional survey was conducted using a anonymous questionnaire. A two-stage
      stratified and cluster random sampling method was used. Approximately one hundred
      pupils from each of four schools agreed to participate in the study, providing a
      total sample size of 403 pupils of which 369 were ultimately included for data
      analysis. The response rate was 98%. Structural equation modeling was used to
      analyse hypothesized paths. RESULTS: The TPB model used in this study was
      effective in predicting protective sexual behavior among Swazi in-school youths,
      as shown by model fit indices. All hypothesized constructs significantly
      predicted intentions for abstinence and condom use, except perceived abstinence
      controls. Subjective norms were the strongest predictors of intention for
      premarital sexual abstinence; however, perceived controls for condom use were the
      strongest predictors of intention for condom use. CONCLUSIONS: Our findings
      support application of the model in predicting determinants of condom use and
      abstinence intentions among Swazi in-school youths.

PMID- 23861758
TI  - 3-dimensional diffusion tensor imaging (DTI) atlas of the rat brain.
AB  - Anatomical atlases play an important role in the analysis of neuroimaging data in
      rodent neuroimaging studies. Having a high resolution, detailed atlas not only
      can expand understanding of rodent brain anatomy, but also enables automatic
      segmentation of new images, thus greatly increasing the efficiency of future
      analysis when applied to new data. These atlases can be used to analyze new scans
      of individual cases using a variety of automated segmentation methods. This
      project seeks to develop a set of detailed 3D anatomical atlases of the brain at
      postnatal day 5 (P5), 14 (P14), and adults (P72) in Sprague-Dawley rats. Our
      methods consisted of first creating a template image based on fixed scans of
      control rats, then manually segmenting various individual brain regions on the
      template. Using itk-SNAP software, subcortical and cortical regions, including
      both white matter and gray matter structures, were manually segmented in the
      axial, sagittal, and coronal planes. The P5, P14, and P72 atlases had 39, 45, and
      29 regions segmented, respectively. These atlases have been made available to the
      broader research community. 

PMID- 23861760
TI  - Risk models to predict hypertension: a systematic review.
AB  - BACKGROUND: As well as being a risk factor for cardiovascular disease,
      hypertension is also a health condition in its own right. Risk prediction models
      may be of value in identifying those individuals at risk of developing
      hypertension who are likely to benefit most from interventions. METHODS AND
      FINDINGS: To synthesize existing evidence on the performance of these models, we
      searched MEDLINE and EMBASE; examined bibliographies of retrieved articles;
      contacted experts in the field; and searched our own files. Dual review of
      identified studies was conducted. Included studies had to report on the
      development, validation, or impact analysis of a hypertension risk prediction
      model. For each publication, information was extracted on study design and
      characteristics, predictors, model discrimination, calibration and
      reclassification ability, validation and impact analysis. Eleven studies
      reporting on 15 different hypertension prediction risk models were identified.
      Age, sex, body mass index, diabetes status, and blood pressure variables were the
      most common predictor variables included in models. Most risk models had
      acceptable-to-good discriminatory ability (C-statistic>0.70) in the derivation
      sample. Calibration was less commonly assessed, but overall acceptable. Two
      hypertension risk models, the Framingham and Hopkins, have been externally
      validated, displaying acceptable-to-good discrimination, and C-statistic ranging
      from 0.71 to 0.81. Lack of individual-level data precluded analyses of the risk
      models in subgroups. CONCLUSIONS: The discrimination ability of existing
      hypertension risk prediction tools is acceptable, but the impact of using these
      tools on prescriptions and outcomes of hypertension prevention is unclear.

PMID- 23861761
TI  - A community of strangers: the dis-embedding of social ties.
AB  - In this paper we explore two contrasting perspectives on individuals'
      participation in associations. On the one hand, some have considered
      participation the byproduct of pre-existing friendship ties--the more friends one
      already has in the association, the more likely he or she is to participate. On
      the other hand, some have considered participation to be driven by the
      association's capacity to form new identities--the more new friends one meets in
      the association, the more likely he or she is to participate. We use detailed
      temporal data from an online association to adjudicate between these two
      mechanisms and explore their interplay. Our results show a significant impact of
      new friendship ties on participation, compared to a negligible impact of pre
      existing friends, defined here as ties to other members formed outside of the
      organization's context. We relate this finding to the sociological literature on
      participation and we explore its implications in the discussion.

PMID- 23861759
TI  - Prenatal loud music and noise: differential impact on physiological arousal,
      hippocampal synaptogenesis and spatial behavior in one day-old chicks.
AB  - Prenatal auditory stimulation in chicks with species-specific sound and music at
      65 dB facilitates spatial orientation and learning and is associated with
      significant morphological and biochemical changes in the hippocampus and
      brainstem auditory nuclei. Increased noradrenaline level due to physiological
      arousal is suggested as a possible mediator for the observed beneficial effects
      following patterned and rhythmic sound exposure. However, studies regarding the
      effects of prenatal high decibel sound (110 dB; music and noise) exposure on the
      plasma noradrenaline level, synaptic protein expression in the hippocampus and
      spatial behavior of neonatal chicks remained unexplored. Here, we report that
      high decibel music stimulation moderately increases plasma noradrenaline level
      and positively modulates spatial orientation, learning and memory of one day-old
      chicks. In contrast, noise at the same sound pressure level results in excessive
      increase of plasma noradrenaline level and impairs the spatial behavior. Further,
      to assess the changes at the molecular level, we have quantified the expression
      of functional synapse markers: synaptophysin and PSD-95 in the hippocampus.
      Compared to the controls, both proteins show significantly increased expressions
      in the music stimulated group but decrease in expressions in the noise group. We
      propose that the differential increase of plasma noradrenaline level and altered
      expression of synaptic proteins in the hippocampus are responsible for the
      observed behavioral consequences following prenatal 110 dB music and noise
      stimulation. 

PMID- 23861762
TI  - Elucidation of miRNAs-mediated responses to low nitrogen stress by deep
      sequencing of two soybean genotypes.
AB  - Nitrogen (N) is a major limiting factor in crop production, and plant adaptive
      responses to low N are involved in many post-transcriptional regulation. Recent
      studies indicate that miRNAs play important roles in adaptive responses. However,
      miRNAs in soybean adaptive responses to N limitation have been not reported. We
      constructed sixteen libraries to identify low N-responsive miRNAs on a genome
      wide scale using samples from 2 different genotypes (low N sensitive and low N
      tolerant) subjected to various periods of low nitrogen stress. Using high
      throughput sequencing technology (Illumina-Solexa), we identified 362 known
      miRNAs variants belonging to 158 families and 90 new miRNAs belonging to 55
      families. Among these known miRNAs variants, almost 50% were not different from
      annotated miRNAs in miRBase. Analyses of their expression patterns showed 150
      known miRNAs variants as well as 2 novel miRNAs with differential expressions.
      These differentially expressed miRNAs between the two soybean genotypes were
      compared and classified into three groups based on their expression patterns.
      Predicted targets of these miRNAs were involved in various metabolic and
      regulatory pathways such as protein degradation, carbohydrate metabolism, hormone
      signaling pathway, and cellular transport. These findings suggest that miRNAs
      play important roles in soybean response to low N and contribute to the
      understanding of the genetic basis of differences in adaptive responses to N
      limitation between the two soybean genotypes. Our study provides basis for
      expounding the complex gene regulatory network of these miRNAs. 

PMID- 23861763
TI  - Is Granger causality a viable technique for analyzing fMRI data?
AB  - Multivariate neural data provide the basis for assessing interactions in brain
      networks. Among myriad connectivity measures, Granger causality (GC) has proven
      to be statistically intuitive, easy to implement, and generate meaningful
      results. Although its application to functional MRI (fMRI) data is increasing,
      several factors have been identified that appear to hinder its neural
      interpretability: (a) latency differences in hemodynamic response function (HRF)
      across different brain regions, (b) low-sampling rates, and (c) noise.
      Recognizing that in basic and clinical neuroscience, it is often the change of a
      dependent variable (e.g., GC) between experimental conditions and between normal
      and pathology that is of interest, we address the question of whether there exist
      systematic relationships between GC at the fMRI level and that at the neural
      level. Simulated neural signals were convolved with a canonical HRF, down
      sampled, and noise-added to generate simulated fMRI data. As the coupling
      parameters in the model were varied, fMRI GC and neural GC were calculated, and
      their relationship examined. Three main results were found: (1) GC following HRF
      convolution is a monotonically increasing function of neural GC; (2) this
      monotonicity can be reliably detected as a positive correlation when realistic
      fMRI temporal resolution and noise level were used; and (3) although the
      detectability of monotonicity declined due to the presence of HRF latency
      differences, substantial recovery of detectability occurred after correcting for
      latency differences. These results suggest that Granger causality is a viable
      technique for analyzing fMRI data when the questions are appropriately
      formulated. 

PMID- 23861764
TI  - LKB1 inhibits breast cancer partially through repressing the Hedgehog signaling
      pathway.
AB  - Constitutive activation of the Hedgehog (Hh) signaling pathway has been
      implicated in the development of many human malignancies. Hh targets, such as
      Patched (PTCH), smoothened (SMO), Sonic hedgehog (SHH) and glioma-associated
      oncogene homologue 1 (GLI1), are markers of Hh signaling activation and expressed
      in most Hh-associated tumors. The protein kinase LKB1 has been shown to slow
      proliferation and induce cell-cycle arrest in many cell lines. In this study, we
      observed that activated LKB1 decreased the expression of factors related to Hh
      reporter activity in MDA-MB-231 breast cancer cells, including of SMO, SHH and
      GLI1. In contrast, LKB1 siRNA increased the expression of these target genes. The
      same results were shown to inhibit the Hh factors Sufu and Hip. Furthermore, we
      also observed negative correlation between LKB1 and glioma-associated oncogene
      homologue 1 (GLI1) in three breast cancer cell lines. Meanwhile, LKB1 siRNA
      rescued the inhibition of cell growth by 3-Keto-N-(aminoethyl-N'
      aminocaproyldihydrocinnamoyl) cyclopamine (KAAD-cyclopamine), an antagonist of
      the Hh element SMO, which suggests that LKB1 acts as the downstream of SMO. In
      vivo, LKB1 siRNA increased tumor growth in the mammary fat pad, and the
      expression levels of Hh displayed similar results in vitro. Overexpression of the
      LKB1 protein in human breast cancers is associated with the expression of Hh. We
      found that breast carcinomas with detectable Hh had weak or undetectable
      expression of LKB1, whereas tumors that expressed high levels of LKB1 had
      undetectable Hh signaling. In this study, we find that LKB1 are negatively
      correlated with the expression of Hh related transcription factors. These
      findings suggest that LKB1 may inhibit tumorigenesis by regulating Hh signaling
      in certain cancers. 

PMID- 23861765
TI  - Reflections of two parallel pathways between the hippocampus and neocortex in
      transient global amnesia: a cross-sectional study using DWI and SPECT.
AB  - OBJECTIVES: Two parallel pathways have been proposed between the hippocampus and
      neocortex. Recently, the anterior and posterior hippocampus showed distinct
      connectivity with different cortical areas in an fMRI study. We investigated
      whether the two parallel pathways could be confirmed in patients with transient
      global amnesia (TGA) which is a natural lesion model of a perturbation of the
      hippocampus. In addition, we evaluated the relationship between the location of
      the hippocampal lesion and various clinical variables. METHODS: A consecutive
      series of 37 patients were identified from the TGA registry database of Seoul
      National University Bundang Hospital. Based on the location of the diffusion
      weighted imaging (DWI) lesion along the anterior-posterior axis of the
      hippocampus, they were divided into the following three groups: head (n = 15),
      body (n = 15) or tail (n = 7). To evaluate which cortical regions showed
      hypoperfusion according to the location of the DWI lesion, their SPECT images
      were compared between two groups using statistical parametric mapping. We
      performed hierarchical cluster analysis to group demographic and clinical
      variables, including the location of the DWI lesion, into clusters. RESULTS:
      Statistical parametric mapping analyses revealed that more anterior DWI lesions
      were associated with hypoperfusion of the anterior temporal and frontal areas,
      whereas more posterior lesions were associated with hypoperfusion of the
      posterior temporal, parietal, occipital and cerebellar areas. The difference was
      most prominent between the group of hippocampal lesions on the head and tail.
      Hierarchical cluster analysis demonstrated that vomiting was related to female
      gender and hippocampal head lesions, whereas vascular risk factors were related
      to male gender and hippocampal body lesions. CONCLUSIONS: We confirmed the
      parallel pathways between the hippocampus and neocortex with DWI and SPECT images
      of patients with TGA. Patients with hippocampal head lesions and body lesions
      were clustered within different groups of clinical variables.

PMID- 23861766
TI  - Cognitive manic symptoms in bipolar disorder associated with polymorphisms in the
      DAOA and COMT genes.
AB  - INTRODUCTION: Bipolar disorder is characterized by severe mood symptoms including
      major depressive and manic episodes. During manic episodes, many patients show
      cognitive dysfunction. Dopamine and glutamate are important for cognitive
      processing, thus the COMT and DAOA genes that modulate the expression of these
      neurotransmitters are of interest for studies of cognitive function. METHODOLOGY:
      Focusing on the most severe episode of mania, a factor was found with the
      combined symptoms of talkativeness, distractibility, and thought disorder,
      considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped,
      out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372
      (76%) thought disorder. 215 (44%) patients were positive for all three symptoms,
      thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors
      (ABD) were used. Case-case and case-control design models were used to
      investigate genetic associations between cognitive manic symptoms in bipolar 1
      disorder and SNPs in the COMT and DAOA genes. [Table: see text]. RESULTS: The
      finding of this study was that cognitive manic symptoms in patients with bipolar
      1 disorder was associated with genetic variants in the DAOA and COMT genes.
      Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in
      bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3)
      analyses. Genotypic association analyses also supported our findings. However,
      only one association, when CMS patients were compared to ABD controls, survived
      correction for multiple testing by max (T) permutation. Data also suggested
      interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case
      control model. [Table: see text] [Table: see text]. CONCLUSION: Identifying genes
      associated with cognitive functioning has clinical implications for assessment of
      prognosis and progression. Our finding are consistent with other studies showing
      genetic associations between the COMT and DAOA genes and impaired cognition both
      in psychiatric disorders and in the general population.

PMID- 23861767
TI  - Trypanosoma cruzi infection in neotropical wild carnivores (Mammalia: Carnivora):
      at the top of the T. cruzi transmission chain.
AB  - Little is known on the role played by Neotropical wild carnivores in the
      Trypanosoma cruzi transmission cycles. We investigated T. cruzi infection in wild
      carnivores from three sites in Brazil through parasitological and serological
      tests. The seven carnivore species examined were infected by T. cruzi, but high
      parasitemias detectable by hemoculture were found only in two Procyonidae
      species. Genotyping by Mini-exon gene, PCR-RFLP (1f8/Akw21I) and kDNA genomic
      targets revealed that the raccoon (Procyon cancrivorus) harbored TcI and the
      coatis (Nasua nasua) harbored TcI, TcII, TcIII-IV and Trypanosoma rangeli, in
      single and mixed infections, besides four T. cruzi isolates that displayed odd
      band patterns in the Mini-exon assay. These findings corroborate the coati can be
      a bioaccumulator of T. cruzi Discrete Typing Units (DTU) and may act as a
      transmission hub, a connection point joining sylvatic transmission cycles within
      terrestrial and arboreal mammals and vectors. Also, the odd band patterns
      observed in coatis' isolates reinforce that T. cruzi diversity might be much
      higher than currently acknowledged. Additionally, we assembled our data with T.
      cruzi infection on Neotropical carnivores' literature records to provide a
      comprehensive analysis of the infection patterns among distinct carnivore
      species, especially considering their ecological traits and phylogeny.
      Altogether, fifteen Neotropical carnivore species were found naturally infected
      by T. cruzi. Species diet was associated with T. cruzi infection rates,
      supporting the hypothesis that predator-prey links are important mechanisms for
      T. cruzi maintenance and dispersion in the wild. Distinct T. cruzi infection
      patterns across carnivore species and study sites were notable. Musteloidea
      species consistently exhibit high parasitemias in different studies which
      indicate their high infectivity potential. Mesocarnivores that feed on both
      invertebrates and mammals, including the coati, a host that can be bioaccumulator
      of T. cruzi DTU's, seem to take place at the top of the T. cruzi transmission
      chain. 

PMID- 23861768
TI  - A nationwide cohort study of mortality risk and long-term prognosis in infective
      endocarditis in Sweden.
AB  - OBJECTIVES: Infective endocarditis (IE) remains a serious disease with
      substantial mortality. In this study we investigated the incidence of IE, as well
      as its associated short and long term mortality rates. METHODS: The IE cases were
      identified in the Swedish national inpatient register using ICD-10 codes, and
      then linked to the population register in order to identify deaths in the cohort.
      Crude mortality rates among IE patients were obtained for different time
      intervals. These rates were directly standardized using sex- and age-matched
      mortality in the general population. RESULTS: The cohort consisted of 7603
      individuals and 7817 episodes of IE during 1997-2007. The 30 days all-cause crude
      mortality rate was 10.4% and the standardized mortality ratio (SMR) was 33.7 (95%
      confidence interval [CI]: 31.0-36.6). Excluding the first year of follow-up, the
      long term mortality (1-5 years) showed an increased SMR of 2.2 (95% CI: 2.0-2.3)
      compared to the general population. Significantly higher SMR was found for cases
      of IE younger than 65 years of age with a 1-5 year SMR of 6.3, and intravenous
      drug-users with a SMR of 19.1. Native valve IE cases, in which surgery was
      performed had lower crude mortality rates and Mantel-Haenzel odds ratios of less
      than one compared to those with medical therapy alone during 30-day and 5-years
      follow-up. CONCLUSIONS: The 30-days crude mortality rate for IE was 10.4% and
      long-term relative mortality risk remains increased even up to 5 years of follow
      up, therefore a close monitoring of these patients would be of value.

PMID- 23861769
TI  - Opto-mechanical coupling in interfaces under static and propagative conditions
      and its biological implications.
AB  - Fluorescent dyes are vital for studying static and dynamic patterns and pattern
      formation in cell biology. Emission properties of the dyes incorporated in a
      biological interface are known to be sensitive to their local environment. We
      report that the fluorescence intensity of dye molecules embedded in lipid
      interfaces is indeed a thermodynamic observable of the system. Opto-mechanical
      coupling of lipid-dye system was measured as a function of the thermodynamic
      state of the interface. The corresponding state diagrams quantify the
      thermodynamic coupling between intensity I and lateral pressure pi. We further
      demonstrate that the coupling is conserved upon varying the temperature T.
      Notably, the observed opto-mechanical coupling is not limited to equilibrium
      conditions, but also holds for propagating pressure pulses. The non-equilibrium
      data show, that fluorescence is especially sensitive to dynamic changes in state
      such as the LE-LC phase transition. We conclude that variations in the
      thermodynamic state (here pi and T, in general pH, membrane potential V, etc
      also) of lipid membranes are capable of controlling fluorescence intensity.
      Therefore, interfacial thermodynamic state diagrams of I should be obtained for a
      proper interpretation of intensity data. 

PMID- 23861770
TI  - RNA sequencing of the human milk fat layer transcriptome reveals distinct gene
      expression profiles at three stages of lactation.
AB  - Aware of the important benefits of human milk, most U.S. women initiate
      breastfeeding but difficulties with milk supply lead some to quit earlier than
      intended. Yet, the contribution of maternal physiology to lactation difficulties
      remains poorly understood. Human milk fat globules, by enveloping cell contents
      during their secretion into milk, are a rich source of mammary cell RNA. Here, we
      pair this non-invasive mRNA source with RNA-sequencing to probe the milk fat
      layer transcriptome during three stages of lactation: colostral, transitional,
      and mature milk production. The resulting transcriptomes paint an exquisite
      portrait of human lactation. The resulting transcriptional profiles cluster not
      by postpartum day, but by milk Na:K ratio, indicating that women sampled during
      similar postpartum time frames could be at markedly different stages of gene
      expression. Each stage of lactation is characterized by a dynamic range (10(5)
      fold) in transcript abundances not previously observed with microarray
      technology. We discovered that transcripts for isoferritins and cathepsins are
      strikingly abundant during colostrum production, highlighting the potential
      importance of these proteins for neonatal health. Two transcripts, encoding beta
      casein (CSN2) and alpha-lactalbumin (LALBA), make up 45% of the total pool of
      mRNA in mature lactation. Genes significantly expressed across all stages of
      lactation are associated with making, modifying, transporting, and packaging milk
      proteins. Stage-specific transcripts are associated with immune defense during
      the colostral stage, up-regulation of the machinery needed for milk protein
      synthesis during the transitional stage, and the production of lipids during
      mature lactation. We observed strong modulation of key genes involved in lactose
      synthesis and insulin signaling. In particular, protein tyrosine phosphatase,
      receptor type, F (PTPRF) may serve as a biomarker linking insulin resistance with
      insufficient milk supply. This study provides the methodology and reference data
      set to enable future targeted research on the physiological contributors of sub
      optimal lactation in humans. 

PMID- 23861771
TI  - Preparation of 5'-O-(1-Thiotriphosphate)-modified oligonucleotides using
      polymerase-endonuclease amplification reaction (PEAR).
AB  - Antisense oligonucleotides (ASODNs) have been widely used as an important tool
      for regulating gene expression, and developed into therapeutics. Natural ODNs are
      susceptible to nuclease degradation, nucleic acid analogues, however, have less
      side effects, stronger stability and more potent activities. Large-scale de novo
      synthesis of a certain oligonucleotide has been very difficult and costly. In a
      previous preliminary study, we developed the polymerase-endonuclease
      amplification reaction (PEAR) for amplification and large-scale preparation of
      natural antisense ODNs. Here we extended the method in preparation of a widely
      used modified oligonucleotide with 5'-O-(1-Thiotriphosphate) modifications. Using
      electrospray ionization liquid chromatography mass spectrometry (ESI/LC/MS)
      detection, the purity of the PEAR product was measured as high as 100.0%. Using
      PEAR a large amount of a specific oligonucleotide can be produced starting from a
      small amount of synthetic seeds. It is suggested that PEAR can be a useful tool
      for large-scale production of modified oligonucleotides. 

PMID- 23861772
TI  - Financing HIV programming: how much should low- and middle-income countries and
      their donors pay?
AB  - Global HIV control funding falls short of need. To maximize health outcomes, it
      is critical that national governments sustain reasonable commitments, and that
      international donor assistance be distributed according to country needs and
      funding gaps. We develop a country classification framework in terms of actual
      versus expected national domestic funding, considering resource needs and donor
      financing. With UNAIDS and World Bank data, we examine domestic and donor HIV
      program funding in relation to need in 84 low- and middle-income countries. We
      estimate expected domestic contributions per person living with HIV (PLWH) as a
      function of per capita income, relative size of the health sector, and per capita
      foreign debt service. Countries are categorized according to levels of actual
      versus expected domestic contributions, and resource gap. Compared to national
      resource needs (UNAIDS Investment Framework), we identify imbalances among
      countries in actual versus expected domestic and donor contributions: 17
      countries, with relatively high HIV prevalence and GNI per capita, have domestic
      funding below expected (median per PLWH $143 and $376, respectively), yet total
      available funding including from donors would exceed the need ($368 and $305,
      respectively) if domestic contribution equaled expected. Conversely, 27 countries
      have actual domestic funding above the expected (medians $294 and $149) but total
      (domestic+donor) funding does not meet estimated need ($685 and $1,173). Across
      the 84 countries, in 2009, estimated resource need totaled $10.3 billion, actual
      domestic contributions $5.1 billion and actual donor contributions $3.7 billion.
      If domestic contributions would increase to the expected level in countries where
      the actual was below expected, total domestic contributions would increase to
      $7.4 billion, turning a funding gap of $1.5 billion into a surplus of $0.8
      billion. Even with imperfect funding and resource-need data, the proposed country
      classification could help improve coherence and efficiency in domestic and
      international allocations. 

PMID- 23861773
TI  - Dynamics of the full length and mutated heat shock factor 1 in human cells.
AB  - Heat shock factor 1 is the key transcription factor of the heat shock response.
      Its function is to protect the cell against the deleterious effects of stress.
      Upon stress, HSF1 binds to and transcribes hsp genes and repeated satellite III
      (sat III) sequences present at the 9q12 locus. HSF1 binding to pericentric sat
      III sequences forms structures known as nuclear stress bodies (nSBs). nSBs
      represent a natural amplification of RNA pol II dependent transcription sites.
      Dynamics of HSF1 and of deletion mutants were studied in living cells using multi
      confocal Fluorescence Correlation Spectroscopy (mFCS) and Fluorescence Recovery
      After Photobleaching (FRAP). In this paper, we show that HSF1 dynamics
      modifications upon heat shock result from both formation of high molecular weight
      complexes and increased HSF1 interactions with chromatin. These interactions
      involve both DNA binding with Heat Shock Element (HSE) and sat III sequences and
      a more transient sequence-independent binding likely corresponding to a search
      for more specific targets. We find that the trimerization domain is required for
      low affinity interactions with chromatin while the DNA binding domain is required
      for site-specific interactions of HSF1 with DNA. 

PMID- 23861774
TI  - Effect of acute exercise on prostate cancer cell growth.
AB  - Physical activity is associated with reduced risk of several cancers, including
      aggressive prostate cancer. The mechanisms mediating the effects are not yet
      understood; among the candidates are modifications of endogenous hormone levels.
      Long-term exercise is known to reduce serum levels of growth stimulating
      hormones. In contrast, the endocrine effects of acute endurance exercise include
      increased levels of mitogenic factors such as GH and IGF-1. It can be speculated
      that the elevation of serum growth factors may be detrimental to prostate cancer
      progression into malignancy. The incentive of the current study is to evaluate
      the effect of acute exercise serum on prostate cancer cell growth. We designed an
      exercise intervention where 10 male individuals performed 60 minutes of bicycle
      exercise at increasing intensity. Serum samples were obtained before (rest serum)
      and after completed exercise (exercise serum). The established prostate cancer
      cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out
      of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with
      pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre
      incubation before subcutaneous injection into SCID mice caused a delay in tumor
      formation. Serum analyses indicated two possible candidates for the effect;
      increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the
      fear of possible detrimental effects of acute exercise serum on tumor cell
      growth, we show that even the short-term effects seem to add to the overall
      beneficial influence of exercise on neoplasia. 

PMID- 23861775
TI  - miR-26a and its target CKS2 modulate cell growth and tumorigenesis of papillary
      thyroid carcinoma.
AB  - BACKGROUND: While many studies have shown that levels of miR-26a are lower in
      papillary thyroid carcinoma (PTC), the role and mechanism of miR-26a in PTC are
      unclear. METHOD: We used database searches to select potential mRNA targets of
      miR-26a. Anti-miR-26a, miR-26a mimic, siRNA for CKS2 and their effects on cell
      growth, cell-cycle distribution and colony formation were evaluated. We also
      evaluate the over-expressed miR-26a in TPC-1 cells in severe combined immune
      deficient mice. We used luciferase reporter assays, real-time PCR and western
      blot analysis to measure the expression and activity of miR-26a, CKS2, and
      related factors such as cyclin B1, cyclin A, cdk1, bcl-xl and Akt. Finally, we
      measured the relationship between the levels of miR-26a and CKS2 in PTC and
      normal thyroid tissues. RESULTS: Relative to normal thyroid tissues, miR-26a is
      consistently down-regulated in TPC specimens, and CKS2 was identified as a
      potential target. Up-regulated miR-26a expression or down-regulated CKS2
      expression in TPC-1 and CGTH W3 cells lines caused G2 phase-arrest. Decreased miR
      26a expression or increased CKS2 expression could have inverse function on PTC
      cell lines. CyclinB1, cyclinA, bcl-xl and AKt are indirectly regulated by miR-26a
      in a CKS2-dependent manner. Finally, CKS2 is overexpressed in PTC specimens
      relative to normal thyroid tissue, and a significant inverse correlation exists
      between miR-26a and CKS2 expression in clinical PTC specimens. CONCLUSION: Our
      data indicate that miR-26a functions as a growth-suppressive miRNA in PTC, and
      that its suppressive effects are mediated mainly by repressing CKS2 expression.

PMID- 23861776
TI  - Specialized yeast ribosomes: a customized tool for selective mRNA translation.
AB  - Evidence is now accumulating that sub-populations of ribosomes - so-called
      specialized ribosomes - can favour the translation of subsets of mRNAs. Here we
      use a large collection of diploid yeast strains, each deficient in one or other
      copy of the set of ribosomal protein (RP) genes, to generate eukaryotic cells
      carrying distinct populations of altered 'specialized' ribosomes. We show by
      comparative protein synthesis assays that different heterologous mRNA reporters
      based on luciferase are preferentially translated by distinct populations of
      specialized ribosomes. These mRNAs include reporters carrying premature
      termination codons (PTC) thus allowing us to identify specialized ribosomes that
      alter the efficiency of translation termination leading to enhanced synthesis of
      the wild-type protein. This finding suggests that these strains can be used to
      identify novel therapeutic targets in the ribosome. To explore this further we
      examined the translation of the mRNA encoding the extracellular matrix protein
      laminin beta3 (LAMB3) since a LAMB3-PTC mutant is implicated in the blistering
      skin disease Epidermolysis bullosa (EB). This screen identified specialized
      ribosomes with reduced levels of RP L35B as showing enhanced synthesis of full
      length LAMB3 in cells expressing the LAMB3-PTC mutant. Importantly, the RP L35B
      sub-population of specialized ribosomes leave both translation of a reporter
      luciferase carrying a different PTC and bulk mRNA translation largely unaltered. 

PMID- 23861777
TI  - Balancing evidence and uncertainty when considering rubella vaccine introduction.
AB  - BACKGROUND: Despite a safe and effective vaccine, rubella vaccination programs
      with inadequate coverage can raise the average age of rubella infection; thereby
      increasing rubella cases among pregnant women and the resulting congenital
      rubella syndrome (CRS) in their newborns. The vaccination coverage necessary to
      reduce CRS depends on the birthrate in a country and the reproductive number, R0,
      a measure of how efficiently a disease transmits. While the birthrate within a
      country can be known with some accuracy, R0 varies between settings and can be
      difficult to measure. Here we aim to provide guidance on the safe introduction of
      rubella vaccine into countries in the face of substantial uncertainty in R0.
      METHODS: We estimated the distribution of R0 in African countries based on the
      age distribution of rubella infection using Bayesian hierarchical models. We
      developed an age specific model of rubella transmission to predict the level of
      R0 that would result in an increase in CRS burden for specific birth rates and
      coverage levels. Combining these results, we summarize the safety of introducing
      rubella vaccine across demographic and coverage contexts. FINDINGS: The median R0
      of rubella in the African region is 5.2, with 90% of countries expected to have
      an R0 between 4.0 and 6.7. Overall, we predict that countries maintaining routine
      vaccination coverage of 80% or higher are can be confident in seeing a reduction
      in CRS over a 30 year time horizon. CONCLUSIONS: Under realistic assumptions
      about human contact, our results suggest that even in low birth rate settings
      high vaccine coverage must be maintained to avoid an increase in CRS. These
      results lend further support to the WHO recommendation that countries reach 80%
      coverage for measles vaccine before introducing rubella vaccination, and
      highlight the importance of maintaining high levels of vaccination coverage once
      the vaccine is introduced.

PMID- 23861779
TI  - The correlation analysis of two common polymorphisms in STAT6 gene and the risk
      of asthma: a meta-analysis.
AB  - BACKGROUND: Several studies have reported that the GT dinucleotide repeat length
      polymorphism and the G2964A polymorphism in signal transducer and activator of
      transcriptional factor 6 gene are associated with asthma susceptibility, but
      others have conflicting results. Our meta-analysis aimed to elucidate the
      emerging paradigms. METHODS: We searched PUBMED, EMBASE, ISI web of knowledge,
      Chinese National Knowledge Infrastructure, and Wanfang databases. Odds ratios
      (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the strength
      of association. We applied Bonferroni step-down and Benjamini-Hochberg step-up
      methods to adjust the values for multiple comparisons. RESULTS: A total of 12
      individual studies in 11 articles were included in the meta-analysis. For GT
      repeat polymorphism, the S allele had approximately 45% increased risk of asthma
      (S vs. L: OR  =  1.45, 95% CI  =  1.22-1.71, P(UNCORRECTED) < 0.001, P(Bon) <
      0.001, P(FDR) < 0.001). Further analysis indicated that GT13 and GT14 contributed
      to asthma risk, whereas GT15 and GT16 were protective (GT13 vs. GT15: OR  = 
      1.38, 95% CI  =  1.16-1.65, P(UNCORRECTED ) =  0.001, P(Bon) =  0.005, P(FDR) = 
      0.002). Similar results were obtained in the subgroup analysis of Asian
      population. G2964A polymorphism analysis showed that the AA genotype moderately
      increased the risk of asthma by 47% compared with the GG genotype (OR  =  1.47, p
      =  0.068) in Chinese population, whereas the 2964A allele moderately increased
      the risk of asthma in Chinese population by 18% (2964A vs. 2964G: OR  =  1.18, p 
      =  0.08). However, none of the associations reached statistically significant
      levels particularly after correction for multiple testing. CONCLUSIONS: This meta
      analysis suggests that S allele (GT13 and GT14) of the GT repeat polymorphism
      confers significant risks to asthma. However, the G2964A polymorphism does not
      have an association with the susceptibility to asthma.

PMID- 23861778
TI  - Systematic dissection of the agrobacterium type VI secretion system reveals
      machinery and secreted components for subcomplex formation.
AB  - The type VI secretion system (T6SS) is widely distributed in pathogenic
      Proteobacteria. Sequence and structural analysis of T6SS reveals a resemblance to
      the T4 bacteriophage tail, in which an outer sheath structure contracts an
      internal tube for injecting nucleic acid into bacterial cells. However, the
      molecular details of how this phage tail-like T6SS structure is assembled in vivo
      and executed for exoprotein or effector secretion remain largely unknown. Here,
      we used a systematic approach to identify T6SS machinery and secreted components
      and investigate the interaction among the putative sheath and tube components of
      Agrobacterium tumefaciens. We showed that 14 T6SS components play essential roles
      in the secretion of the T6SS hallmark exoprotein Hcp. In addition, we discovered
      a novel T6SS exoprotein, Atu4347, that is dispensable for Hcp secretion.
      Interestingly, Atu4347 and the putative tube components, Hcp and VgrG, are mainly
      localized in the cytoplasm but also detected on the bacterial surface. Atu4342
      (TssB) and Atu4341 (TssC41) interact with and stabilize each other, which
      suggests that they are functional orthologs of the sheath components TssB (VipA)
      and TssC (VipB), respectively. Importantly, TssB interacts directly with the
      three exoproteins (Hcp, VgrG, and Atu4347), in which Hcp also interacts directly
      with VgrG-1 on co-purification from Escherichia coli. Further co
      immunoprecipitation and pulldown assays revealed these subcomplex(es) in A.
      tumefaciens and thereby support T6SS functioning as a contractile phage tail-like
      structure. 

PMID- 23861781
TI  - Sex-specific effects on spatial learning and memory, and sex-independent effects
      on blood pressure of a <3.3 Mbp rat chromosome 2 QTL region in Dahl salt
      sensitive rats.
AB  - Epidemiological studies have consistently found that hypertension is associated
      with poor cognitive performance. We hypothesize that a putative causal mechanism
      underlying this association is due to genetic loci affecting both blood pressure
      and cognition. Consistent with this notion, we reported several blood pressure
      (BP) quantitative trait loci (QTLs) that co-localized with navigational
      performance (Nav)-QTLs influencing spatial learning and memory in Dahl rats. The
      present study investigates a chromosome 2 region harboring BP-f4 and Nav-8 QTLs.
      We developed two congenic strains, S.R2A and S.R2B introgressing Dahl R
      chromosome 2 segments into Dahl S chromosome 2 region spanning BP-f4 and Nav-8
      QTLs. Radiotelemetric blood pressure analysis identified only S.R2A congenic rats
      with lower systolic blood pressure (females: -26.0 mmHg, P = 0.003; males: -30.9
      mmHg, P<1*10(-5)), diastolic blood pressure (females: -21.2 mmHg, P = 0.01;
      males: -25.7 mmHg, P<1*10(-5)), and mean arterial pressure (females: -23.9 mmHg,
      P = 0.004; males: -28.0 mmHg, P<1*10(-5)) compared with corresponding Dahl S
      controls, confirming the presence of BP-f4 QTL on rat chromosome 2. The S.R2B
      congenic segment did not affect blood pressure. Testing of S.R2A, S.R2B, and Dahl
      S male rats in the Morris water maze (MWM) task revealed significantly decreased
      spatial navigation performance in S.R2A male congenic rats when compared with
      Dahl S male controls (P<0.05). The S.R2B congenic segment did not affect
      performance of the MWM task in males. The S.R2A female rats did not differ in
      spatial navigation when compared with Dahl S female controls, indicating that the
      Nav-8 effect on spatial navigation is male-specific. Our results suggest the
      existence of a single QTL on chromosome 2 176.6-179.9 Mbp region which affects
      blood pressure in both males and females and cognition solely in males. 

PMID- 23861780
TI  - Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine
      kinase/ganciclovir gene therapy via enhanced gap junctional intercellular
      communication.
AB  - The bystander effect is an intriguing phenomenon by which adjacent cells become
      sensitized to drug treatment during gene therapy with herpes simplex virus
      thymidine kinase/ganciclovir (HSV-tk/GCV). This effect is reported to be mediated
      by gap junctional intercellular communication (GJIC), and therefore, we
      postulated that upregulation of genes that facilitate GJIC may enhance the HSV
      tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA), a
      chemical substance derived from a Chinese medicine herb, promotes the
      upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions
      are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our
      results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more
      efficient GCV-induced bystander killing in cells stably expressing HSV-tk.
      Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV
      tk positive B16 cells and 90% wild-type B16 cells became smaller following
      treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA
      alone. These data demonstrate that Tan IIA can augment the bystander effect of
      HSV-tk/GCV system through increased gap junction coupling, which adds strength to
      the promising strategy that develops connexins inducer to potentiate the effects
      of suicide gene therapy. 

PMID- 23861782
TI  - Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) significantly
      improve prostate cancer detection at initial biopsy in a total PSA range of 2-10
      ng/ml.
AB  - Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and
      overtreatment have been made. To this aim, Prostate Health Index (Phi) and
      Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific
      biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer
      (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The
      performance of phi and PCA3 were evaluated in 300 patients undergoing first
      prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in
      predicting PCa. Decision curve analyses (DCA) were used to compare the clinical
      benefit of the two biomarkers. We found that the AUC value of phi (0.77) was
      comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant
      differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p =
      0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly
      outperformed fPSA (AUC = 0.60), % fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At
      DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold
      probability of 25%, then phi index showed higher net benefit than PCA3.
      Multivariable analysis showed that the addition of phi and PCA3 to the base
      multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive
      accuracy, whereas no model improved single biomarker performance. Finally we
      showed that subjects with active surveillance (AS) compatible cancer had
      significantly lower phi and PCA3 values (p<0.001 and p = 0.01, respectively). In
      conclusion, both phi and PCA3 comparably increase the accuracy in predicting the
      presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming
      currently used %fPSA. 

PMID- 23861783
TI  - Lipocalin-2 expressed in innate immune cells is an endogenous inhibitor of
      inflammation in murine nephrotoxic serum nephritis.
AB  - Lipocalin-2 (Lcn-2) is involved in divergent processes such as acute kidney
      injury or bacterial host defence. Our study was designed to evaluate the
      functional role of Lcn-2 in nephrotoxic serum nephritis (NTS). Since Lcn-2 is
      expressed in tubular epithelial cells as well as in cells of innate immunity such
      as macrophages and polymorphonuclear neutrophils (PMN), we induced NTS in wild
      type (WT), Lcn-2 knock-out (KO) mice and WT/Lcn-2 KO chimeras. Mice lacking Lcn-2
      exhibited more glomerular damage with increased proteinuria and interstitial
      leukocyte accumulation compared to WT mice. Chimeras able to express Lcn-2 in
      macrophages and PMN but not in epithelial cells were found to develop NTS
      comparable to wild-type controls. In contrast, chimeras expressing Lcn-2 in
      tubular epithelial cells with no expression in innate immune cells developed
      increased NTS due to decreased concerted apoptosis but increased necrosis and
      formation of damage-associated molecular patterns (DAMPs) such as high-mobility
      group box 1 (HMGB-1) in the kidney. In vivo blockade of HMGB-1, a toll-like
      receptor (TLR)-2 agonist, significantly reduced inflammation and NTS in Lcn-2
      knock-out mice. In parallel, TLR-2 signalling was found to drive Lcn-2
      transcription in vitro. Taken together, Lcn-2 expressed in innate immune cells is
      protective in NTS by inducing concerted apoptosis and inhibiting the formation of
      HMGB-1 thereby limiting cytokine production via TLR-2 signalling. In parallel,
      TLR-2 dependent transcription of Lcn-2 is an endogenous inhibitor of inflammation
      in NTS. 

PMID- 23861784
TI  - Neural correlates of speech processing in prelingually deafened children and
      adolescents with cochlear implants.
AB  - Prelingually deafened children with cochlear implants stand a good chance of
      developing satisfactory speech performance. Nevertheless, their eventual language
      performance is highly variable and not fully explainable by the duration of
      deafness and hearing experience. In this study, two groups of cochlear implant
      users (CI groups) with very good basic hearing abilities but non-overlapping
      speech performance (very good or very bad speech performance) were matched
      according to hearing age and age at implantation. We assessed whether these CI
      groups differed with regard to their phoneme discrimination ability and auditory
      sensory memory capacity, as suggested by earlier studies. These functions were
      measured behaviorally and with the Mismatch Negativity (MMN). Phoneme
      discrimination ability was comparable in the CI group of good performers and
      matched healthy controls, which were both better than the bad performers. Source
      analyses revealed larger MMN activity (155-225 ms) in good than in bad
      performers, which was generated in the frontal cortex and positively correlated
      with measures of working memory. For the bad performers, this was followed by an
      increased activation of left temporal regions from 225 to 250 ms with a focus on
      the auditory cortex. These results indicate that the two CI groups developed
      different auditory speech processing strategies and stress the role of
      phonological functions of auditory sensory memory and the prefrontal cortex in
      positively developing speech perception and production. 

PMID- 23861785
TI  - Mannitol utilisation is required for protection of Staphylococcus aureus from
      human skin antimicrobial fatty acids.
AB  - Mannitol (Mtl) fermentation, with the subsequent production of acid, is a species
      signature of Staphylococcus aureus, and discriminates it from most other members
      of the genus. Inactivation of the gene mtlD, encoding Mtl-1-P dehydrogenase was
      found to markedly reduce survival in the presence of the antimicrobial fatty
      acid, linoleic acid. We demonstrate that the sugar alcohol has a potentiating
      action for this membrane-acting antimicrobial. Analysis of cellular metabolites
      revealed that, during exponential growth, the mtlD mutant accumulated high levels
      of Mtl and Mtl-P. The latter metabolite was not detected in its isogenic parent
      strain or a deletion mutant of the entire mtlABFD operon. In addition, the mtlD
      mutant strain exhibited a decreased MIC for H2O2, however virulence was
      unaffected in a model of septic arthritis. 

PMID- 23861786
TI  - Collective chasing behavior between cooperators and defectors in the spatial
      prisoner's dilemma.
AB  - Cooperation is one of the essential factors for all biological organisms in major
      evolutionary transitions. Recent studies have investigated the effect of
      migration for the evolution of cooperation. However, little is known about
      whether and how an individuals' cooperativeness coevolves with mobility. One
      possibility is that mobility enhances cooperation by enabling cooperators to
      escape from defectors and form clusters; the other possibility is that mobility
      inhibits cooperation by helping the defectors to catch and exploit the groups of
      cooperators. In this study we investigate the coevolutionary dynamics by using
      the prisoner's dilemma game model on a lattice structure. The computer
      simulations demonstrate that natural selection maintains cooperation in the form
      of evolutionary chasing between the cooperators and defectors. First, cooperative
      groups grow and collectively move in the same direction. Then, mutant defectors
      emerge and invade the cooperative groups, after which the defectors exploit the
      cooperators. Then other cooperative groups emerge due to mutation and the cycle
      is repeated. Here, it is worth noting that, as a result of natural selection, the
      mobility evolves towards directional migration, but not to random or completely
      fixed migration. Furthermore, with directional migration, the rate of global
      population extinction is lower when compared with other cases without the
      evolution of mobility (i.e., when mobility is preset to random or fixed). These
      findings illustrate the coevolutionary dynamics of cooperation and mobility
      through the directional chasing between cooperators and defectors. 

PMID- 23861787
TI  - Birth origin differentially affects depressive-like behaviours: are captive-born
      cynomolgus monkeys more vulnerable to depression than their wild-born
      counterparts?
AB  - BACKGROUND: Adverse early-life experience might lead to the expression of
      abnormal behaviours in animals and the predisposition to psychiatric disorder
      (e.g. major depressive disorder) in Humans. Common breeding processes employ
      weaning and housing conditions different from what happens in the wild. METHODS:
      The present study, therefore, investigated whether birth origin impacts the
      possible existence of spontaneous atypical/abnormal behaviours displayed by 40
      captive-born and 40 wild-born socially-housed cynomolgus macaques in farming
      conditions using an unbiased ethological scan-sampling analysis followed by
      multifactorial correspondence and hierarchical clustering analyses. RESULTS: We
      identified 10 distinct profiles (groups A to J) that significantly differed on
      several behaviours, body postures, body orientations, distances between
      individuals and locations in the cage. Data suggest that 4 captive-born and 1
      wild-born animals (groups G and J) present depressive-like symptoms, unnatural
      early life events thereby increasing the risk of developing pathological
      symptoms. General differences were also highlighted between the captive- and wild
      born populations, implying the expression of differential coping mechanisms in
      response to the same captive environment. CONCLUSIONS: Birth origin thus impacts
      the development of atypical ethologically-defined behavioural profiles,
      reminiscent of certain depressive-like symptoms. The use of unbiased behavioural
      observations might allow the identification of animal models of human
      mental/behavioural disorders and their most appropriate control groups.

PMID- 23861788
TI  - Selective modulation of Wnt ligands and their receptors in adipose tissue by
      chronic hyperadiponectinemia.
AB  - BACKGROUND: Adiponectin-transgenic mice had many small adipocytes in both
      subcutaneous and visceral adipose tissues, and showed higher sensitivity to
      insulin, longer life span, and reduced chronic inflammation. We hypothesized that
      adiponectin regulates Wnt signaling in adipocytes and thereby modulates adipocyte
      proliferation and chronic inflammation in adipose tissue. MATERIALS AND METHODS:
      We examined the expression of all Wnt ligands and their receptors and the
      activity of Wnt signaling pathways in visceral adipose tissue from wild-type mice
      and two lines of adiponectin-transgenic mice. The effects of adiponectin were
      also investigated in cultured 3T3-L1 cells. RESULTS: The Wnt5b, Wnt6, Frizzled 6
      (Fzd6), and Fzd9 genes were up-regulated in both lines of transgenic mice,
      whereas Wnt1, Wnt2, Wnt5a, Wnt9b, Wnt10b, Wnt11, Fzd1, Fzd2, Fzd4, Fzd7, and the
      Fzd coreceptor low-density-lipoprotein receptor-related protein 6 (Lrp6) were
      reduced. There was no difference in total beta-catenin levels in whole-cell
      extracts, non-phospho-beta-catenin levels in nuclear extracts, or mRNA levels of
      beta-catenin target genes, indicating that hyperadiponectinemia did not affect
      canonical Wnt signaling. In contrast, phosphorylated calcium/calmodulin-dependent
      kinase II (p-CaMKII) and phosphorylated Jun N-terminal kinase (p-JNK) were
      markedly reduced in adipose tissue from the transgenic mice. The adipose tissue
      of the transgenic mice consisted of many small cells and had increased expression
      of adiponectin, whereas cyclooxygenase-2 expression was reduced. Wnt5b expression
      was elevated in preadipocytes of the transgenic mice and decreased in diet
      induced obese mice, suggesting a role in adipocyte differentiation. Some Wnt
      genes, Fzd genes, and p-CaMKII protein were down-regulated in 3T3-L1 cells
      cultured with a high concentration of adiponectin. CONCLUSION: Chronic
      hyperadiponectinemia selectively modulated the expression of Wnt ligands, Fzd
      receptors and LRP coreceptors accompanied by the inhibition of the Wnt/Ca(2+) and
      JNK signaling pathways, which may be involved in the altered adipocyte
      cellularity, endogenous adiponectin production, and anti-inflammatory action
      induced by hyperadiponectinemia.

PMID- 23861790
TI  - Point charges optimally placed to represent the multipole expansion of charge
      distributions.
AB  - We propose an approach for approximating electrostatic charge distributions with
      a small number of point charges to optimally represent the original charge
      distribution. By construction, the proposed optimal point charge approximation
      (OPCA) retains many of the useful properties of point multipole expansion,
      including the same far-field asymptotic behavior of the approximate potential. A
      general framework for numerically computing OPCA, for any given number of
      approximating charges, is described. We then derive a 2-charge practical point
      charge approximation, PPCA, which approximates the 2-charge OPCA via closed form
      analytical expressions, and test the PPCA on a set of charge distributions
      relevant to biomolecular modeling. We measure the accuracy of the new
      approximations as the RMS error in the electrostatic potential relative to that
      produced by the original charge distribution, at a distance 2x the extent of the
      charge distribution--the mid-field. The error for the 2-charge PPCA is found to
      be on average 23% smaller than that of optimally placed point dipole
      approximation, and comparable to that of the point quadrupole approximation. The
      standard deviation in RMS error for the 2-charge PPCA is 53% lower than that of
      the optimal point dipole approximation, and comparable to that of the point
      quadrupole approximation. We also calculate the 3-charge OPCA for representing
      the gas phase quantum mechanical charge distribution of a water molecule. The
      electrostatic potential calculated by the 3-charge OPCA for water, in the mid
      field (2.8 A from the oxygen atom), is on average 33.3% more accurate than the
      potential due to the point multipole expansion up to the octupole order. Compared
      to a 3 point charge approximation in which the charges are placed on the atom
      centers, the 3-charge OPCA is seven times more accurate, by RMS error. The
      maximum error at the oxygen-Na distance (2.23 A) is half that of the point
      multipole expansion up to the octupole order.

PMID- 23861789
TI  - Wildtype and A30P mutant alpha-synuclein form different fibril structures.
AB  - Parkinson's Disease (PD) is a neurodegenerative movement disorder affecting
      millions of people worldwide. One of the key players in the development of the
      disease is the protein alpha-synuclein (aSN), which aggregates in the brain of PD
      patients. The aSN mutant A30P has been reported to cause early-onset familial PD
      and shows different aggregation behavior compared to wt aSN. Here we use a
      multidisciplinary approach to compare the aggregation process of wt and A30P aSN.
      In agreement with previous studies, we observe an initial lag phase followed by a
      continuous structural development of fibrils until reaching an apparent monomer
      aggregate equilibrium state and a plateau in Thioflavin T (ThT) fluorescence
      intensity. However, at later timepoints A30P shows greater propensity than
      alphaSN wt to form dense bundled fibril networks. Combining small angle x-ray
      scattering, x-ray fibre diffraction and linear dichroism, we demonstrate that
      while the microscopic structure of the individual fibril essentially remains
      constant throughout the experiment, the formation of dense A30P fibril networks
      occur through a continuous assembly pathway while the formation of less dense wt
      fibril networks with fewer contact points follows a continuous path during the
      elongation phase and a second rearrangement phase after reaching the ThT
      fluorescence plateau. Our work thus highlights that structural rearrangements
      proceed beyond the plateau in ThT-based monitoring of the fibrillation process,
      and the density and morphology of the resulting fibril networks is highly
      dependent on the aSN form studied. 

PMID- 23861791
TI  - Being on the field when the game is still under way. The financial press and
      stock markets in times of crisis.
AB  - This paper looks at the relationship between negative news and stock markets in
      times of global crisis, such as the 2008/2009 period. We analysed one year of
      front page banner headlines of three financial newspapers, the Wall Street
      Journal, Financial Times, and Il Sole24ore to examine the influence of bad news
      both on stock market volatility and dynamic correlation. Our results show that
      the press and markets influenced each other in generating market volatility and
      in particular, that the Wall Street Journal had a crucial effect both on the
      volatility and correlation between the US and foreign markets. We also found
      significant differences between newspapers in their interpretation of the crisis,
      with the Financial Times being significantly pessimistic even in phases of low
      market volatility. Our results confirm the reflexive nature of stock markets.
      When the situation is uncertain and unpredictable, market behaviour may even
      reflect qualitative, big picture, and subjective information such as streamers in
      a newspaper, whose economic and informative value is questionable. 

PMID- 23861792
TI  - Proteomic and properties analysis of botanical insecticide rhodojaponin III
      induced response of the diamondback moth, Plutella xyllostella (L.).
AB  - BACKGROUND: Rhodojaponin III, as a botanical insecticide, affects a wide variety
      of biological processes in insects, including reduction of feeding, suspension of
      development, and oviposition deterring of adults in a dose-dependent manner.
      However, the mode of these actions remains obscure. PRINCIPAL FINDINGS: In this
      study, a comparative proteomic approach was adopted to examine the effect of
      rhodojaponin III on the Plutella xyllostella (L.). Following treating 48 hours,
      newly emergence moths were collected and protein samples were prepared. The
      proteins were separated by 2-DE, and total 31 proteins were significantly
      affected by rhodojaponin III compared to the control identified by MALDI-TOF/TOF
      MS/MS. These differentially expressed proteins act in the nervous transduction,
      odorant degradation and metabolic change pathways. Further, gene expression
      patterns in treated and untreated moths were confirmed by qRT-PCR and western
      blot analysis. RNAi of the chemosensory protein (PxCSP) gene resulted in
      oviposition significantly increased on cabbage plants treated with rhodojaponin
      III. CONCLUSIONS: These rhodojaponin III-induced proteins and gene properties
      analysis would be essential for a better understanding of the potential molecular
      mechanism of the response to rhodojaponin III from moths of P. xylostella.

PMID- 23861793
TI  - Introgressive hybridization between anciently diverged lineages of Silene
      (Caryophyllaceae).
AB  - Hybridization has played a major role during the evolution of angiosperms,
      mediating both gene flow between already distinct species and the formation of
      new species. Newly formed hybrids between distantly related taxa are often
      sterile. For this reason, interspecific crosses resulting in fertile hybrids have
      rarely been described to take place after more than a few million years after
      divergence. We describe here the traces of a reproductively successful hybrid
      between two ancestral species of Silene, diverged for about six million years
      prior to hybridization. No extant hybrids between the two parental lineages are
      currently known, but introgression of the RNA polymerase gene NRPA2 provides
      clear evidence of a temporary and fertile hybrid. Parsimony reconciliation
      between gene trees and the species tree, as well as consideration of clade ages,
      help exclude gene paralogy and lineage sorting as alternative hypotheses. This
      may represent one of the most extreme cases of divergence between species prior
      to introgressive hybridization discovered yet, notably at a homoploid level.
      Although species boundaries are generally believed to be stable after millions of
      years of divergence, we believe that this finding may indicate that gene flow
      between distantly related species is merely largely undetected at present. 

PMID- 23861794
TI  - Plant derived aporphinic alkaloid S-(+)-dicentrine induces antinociceptive effect
      in both acute and chronic inflammatory pain models: evidence for a role of TRPA1
      channels.
AB  - S-(+)-dicentrine is an aporphinic alkaloid found in several plant species, mainly
      from Lauraceae family, which showed significant antinociceptive activity in an
      acute model of visceral pain in mice. In this work, we extended the knowledge on
      the antinociceptive properties of S-(+)-dicentrine and showed that this alkaloid
      also attenuates mechanical and cold hypersensitivity associated with cutaneous
      inflammation induced by Complete Freund's Adjuvant in mice. Given orally, S-(+)
      dicentrine (100 mg/kg) reversed CFA-induced mechanical hypersensitivity,
      evaluated as the paw withdrawal threshold to von Frey hairs, and this effect
      lasted up to 2 hours. S-(+)-dicentrine also reversed CFA-induced cold
      hypersensitivity, assessed as the responses to a drop of acetone in the injured
      paw, but did not reverse the heat hypersensitivity, evaluated as the latency time
      to paw withdrawal in the hot plate (50 degrees C). Moreover, S-(+)-dicentrine
      (100 mg/kg, p.o.) was effective in inhibit nociceptive responses to intraplantar
      injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by
      capsaicin, a TRPV1 activator. When administered either by oral or intraplantar
      routes, S-(+)-dicentrine reduced the licking time (spontaneous nociception) and
      increased the latency time to paw withdrawal in the cold plate (cold
      hypersensitivity), both induced by the intraplantar injection of cinnamaldehyde.
      Taken together, our data adds information about antinociceptive properties of S
      (+)-dicentrine in inflammatory conditions, reducing spontaneous nociception and
      attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent
      mechanism. It also indicates that S-(+)-dicentrine might be potentially
      interesting in the development of new clinically relevant drugs for the
      management of persistent pain, especially under inflammatory conditions.

PMID- 23861795
TI  - An observational study of circulating tumor cells and (18)F-FDG PET uptake in
      patients with treatment-naive non-small cell lung cancer.
AB  - INTRODUCTION: We investigated the relationship of circulating tumor cells (CTCs)
      in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by
      (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with
      patient prognosis. MATERIALS & METHODS: We performed a retrospective screen of
      patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy
      prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell
      Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for
      CTC detection and enumeration (defined here as High Definition CTCs or "HD
      CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data
      calibrated across centers in a cross-sectional analysis. RESULTS: We assessed
      seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile
      range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was
      7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether
      across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were
      weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value =
      0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a
      given partial volume corrected SUVmax or tumor diameter there was a wide range of
      detected HD-CTCs in circulation for both early and late stage disease.
      CONCLUSIONS: CTCs are detected frequently in early-stage NSCLC using a non-EpCAM
      mediated approach with a wide range noted for a given level of FDG uptake or
      tumor size. Integrating potentially complementary biomarkers like these with
      traditional patient data may eventually enhance our understanding of clinical, in
      vivo tumor biology in the early stages of this deadly disease.

PMID- 23861796
TI  - Association between transforming growth factor-beta 1 T869C polymorphism and
      ischemic stroke: a meta-analysis.
AB  - OBJECTIVE: To explore the association between transforming growth factor-beta1
      (TGF-beta1) T869C polymorphism and risk of ischemic stroke (IS) by performing a
      meta-analysis based on published articles. METHODS: Systematic electronic
      searches of PubMed, Science Direct, BIOSIS Previews, Chinese Biomedical Database,
      Chinese National Knowledge Infrastructure, and WANFANG Database were performed.
      The strength of the association was calculated by pooled odds ratios (ORs) with
      95% confidence intervals (95%CIs). Subgroup analysis was conducted to explore
      potential sources of heterogeneity. Sensitivity analysis was performed to
      elucidate the stability of the outcomes. Publication bias was evaluated by Begg's
      funnel plot and Egger's test. RESULTS: A total of 6 studies involving 1701 cases
      were included. The overall estimates did not show any significant association
      between TGF-beta1 T869C polymorphism and risk of IS under all genetic models (C
      vs. T: OR = 1.08,95%CI = 0.88-1.32; CC vs. TT:OR = 1.17,95%CI = 0.79-1.72; CT vs.
      TT: OR = 0.91, 95%CI = 0.68-1.22; CC+CT vs. TT: OR = 0.99, 95%CI = 0.73-1.35; CC
      vs. CT+TT: OR = 1.23, 95%CI = 0.95-1.59). Similar lacking associations were
      observed in subgroup analysis based on ethnicity and source of controls. When
      stratified by study design, significant increased association of IS risk was
      found in cohort studies under genetic models except recessive model(C vs. T: OR =
      1.18, 95%CI = 1.05-1.32; CC vs. TT: OR = 1.40, 95%CI = 1.10-1.77; CT vs. TT: OR =
      1.23, 95%CI = 1.02-1.49; CC+CT vs. TT: OR = 1.27, 95%CI = 1.03-1.57; CC vs.
      CT+TT, OR = 1.21, 95%CI = 0.99-1.47), whereas in case-control studies a
      significant decreased risk was detected under heterozygote comparison(CT vs. CC:
      OR = 0.72, 95%CI = 0.57-0.92). However, after correction for multiple testing,
      the associations were observed to be null significant in both cohort and case
      control subgroups among all genetic models. CONCLUSION: This meta-analysis
      suggested that current epidemiological studies of TGF-beta1 T869C polymorphism
      are too inconsistent to draw a conclusion on the association with IS
      susceptibility. Given the small sample size and remarkable between-study
      heterogeneity, further well-designed prospective large-scale studies are
      warranted.

PMID- 23861797
TI  - Autologous bone-marrow mesenchymal stem cell implantation and endothelial
      function in a rabbit ischemic limb model.
AB  - BACKGROUND: The purpose of this study was to determine whether autologous
      mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a
      rabbit ischemic limb model. METHODS: We evaluated the effect of MSC implantation
      on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium
      dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent
      vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted
      (n = 20) or saline was injected as a control group (n = 20). LBF was measured
      using an electromagnetic flowmeter. A total of 10(6) MSCs were implanted into
      each ischemic limb. RESULTS: Histological sections of ischemic muscle showed that
      capillary index (capillary/muscle fiber) was greater in the MSC implantation
      group than in the control group. Laser Doppler blood perfusion index was
      significantly increased in the MSC implantation group compared with that in the
      control group. LBF response to ACh was greater in the MSC group than in the
      control group. After administration of N(G)-nitro-L-arginine, a nitric oxide
      synthase inhibitor, LBF response to ACh was similar in the MSC implantation group
      and control group. Vasodilatory effects of SNP in the two groups were similar.
      CONCLUSIONS: These findings suggest that MSC implantation induces angiogenesis
      and augments endothelium-dependent vasodilation in a rabbit ischemic model
      through an increase in nitric oxide production.

PMID- 23861798
TI  - Towards clinical molecular diagnosis of inherited cardiac conditions: a
      comparison of bench-top genome DNA sequencers.
AB  - BACKGROUND: Molecular genetic testing is recommended for diagnosis of inherited
      cardiac disease, to guide prognosis and treatment, but access is often limited by
      cost and availability. Recently introduced high-throughput bench-top DNA
      sequencing platforms have the potential to overcome these limitations.
      METHODOLOGY/PRINCIPAL FINDINGS: We evaluated two next-generation sequencing (NGS)
      platforms for molecular diagnostics. The protein-coding regions of six genes
      associated with inherited arrhythmia syndromes were amplified from 15 human
      samples using parallelised multiplex PCR (Access Array, Fluidigm), and sequenced
      on the MiSeq (Illumina) and Ion Torrent PGM (Life Technologies). Overall, 97.9%
      of the target was sequenced adequately for variant calling on the MiSeq, and
      96.8% on the Ion Torrent PGM. Regions missed tended to be of high GC-content, and
      most were problematic for both platforms. Variant calling was assessed using 107
      variants detected using Sanger sequencing: within adequately sequenced regions,
      variant calling on both platforms was highly accurate (Sensitivity: MiSeq 100%,
      PGM 99.1%. Positive predictive value: MiSeq 95.9%, PGM 95.5%). At the time of the
      study the Ion Torrent PGM had a lower capital cost and individual runs were
      cheaper and faster. The MiSeq had a higher capacity (requiring fewer runs), with
      reduced hands-on time and simpler laboratory workflows. Both provide significant
      cost and time savings over conventional methods, even allowing for adjunct Sanger
      sequencing to validate findings and sequence exons missed by NGS.
      CONCLUSIONS/SIGNIFICANCE: MiSeq and Ion Torrent PGM both provide accurate variant
      detection as part of a PCR-based molecular diagnostic workflow, and provide
      alternative platforms for molecular diagnosis of inherited cardiac conditions.
      Though there were performance differences at this throughput, platforms differed
      primarily in terms of cost, scalability, protocol stability and ease of use.
      Compared with current molecular genetic diagnostic tests for inherited cardiac
      arrhythmias, these NGS approaches are faster, less expensive, and yet more
      comprehensive.

PMID- 23861799
TI  - Social cognition deficits and psychopathic traits in young people seeking mental
      health treatment.
AB  - Antisocial behaviours and psychopathic traits place an individual at risk for
      criminality, mental illness, substance dependence, and psychosocial dysfunction.
      Social cognition deficits appear to be associated with psychopathic traits and
      are believed to contribute to interpersonal dysfunction. Most research
      investigating the relationship of these traits with social cognition has been
      conducted either in children or adult forensic settings. We investigated whether
      psychopathic traits were associated with social cognition in 91 young people
      presenting for mental healthcare (aged between 15 and 25 years). Participants
      completed symptom severity measures, neuropsychological tests, the Reading the
      Mind in the Eyes Test of social cognition (RMET), and the Antisocial Process
      Screening Device (APSD) to assess psychopathic personality traits. Correlation
      analyses showed poorer social cognition was associated with greater psychopathic
      traits (r = -.36, p = .01). Interestingly, social cognition performance predicted
      unique variance in concurrent psychopathic personality traits above gender, IQ
      sustained attention, and working memory performance. These findings suggest that
      social cognitive impairments are associated with psychopathic tendencies in young
      people presenting for community mental healthcare. Research is needed to
      establish the directionality of this relationship and to determine whether social
      cognition training is an effective treatment amongst young people with
      psychopathic tendencies. 

PMID- 23861800
TI  - Quantification of errors in ordinal outcome scales using shannon entropy: effect
      on sample size calculations.
AB  - OBJECTIVE: Clinical trial outcomes often involve an ordinal scale of subjective
      functional assessments but the optimal way to quantify results is not clear. In
      stroke, the most commonly used scale, the modified Rankin Score (mRS), a range of
      scores ("Shift") is proposed as superior to dichotomization because of greater
      information transfer. The influence of known uncertainties in mRS assessment has
      not been quantified. We hypothesized that errors caused by uncertainties could be
      quantified by applying information theory. Using Shannon's model, we quantified
      errors of the "Shift" compared to dichotomized outcomes using published
      distributions of mRS uncertainties and applied this model to clinical trials.
      METHODS: We identified 35 randomized stroke trials that met inclusion criteria.
      Each trial's mRS distribution was multiplied with the noise distribution from
      published mRS inter-rater variability to generate an error percentage for "shift"
      and dichotomized cut-points. For the SAINT I neuroprotectant trial, considered
      positive by "shift" mRS while the larger follow-up SAINT II trial was negative,
      we recalculated sample size required if classification uncertainty was taken into
      account. RESULTS: Considering the full mRS range, error rate was 26.1%+/-5.31
      (Mean+/-SD). Error rates were lower for all dichotomizations tested using cut
      points (e.g. mRS 1; 6.8%+/-2.89; overall p<0.001). Taking errors into account,
      SAINT I would have required 24% more subjects than were randomized. CONCLUSION:
      We show when uncertainty in assessments is considered, the lowest error rates are
      with dichotomization. While using the full range of mRS is conceptually
      appealing, a gain of information is counter-balanced by a decrease in
      reliability. The resultant errors need to be considered since sample size may
      otherwise be underestimated. In principle, we have outlined an approach to error
      estimation for any condition in which there are uncertainties in outcome
      assessment. We provide the user with programs to calculate and incorporate errors
      into sample size estimation.

PMID- 23861802
TI  - ADAM33 gene polymorphisms and mortality. A prospective cohort study.
AB  - The ADAM33 gene is associated with the pathophysiology of Chronic Obstructive
      Pulmonary Disease (COPD) and atherosclerosis. In this study we investigated all
      cause, COPD and cardiovascular mortality, in relation to single nucleotide
      polymorphisms (SNPs) in ADAM33 (Q_1, S_1, S_2, T_1 and T_2) that were genotyped
      in 1,390 subjects from the Vlagtwedde/Vlaardingen cohort. Participants were
      examined at entry in 1989/1990 and followed up till evaluation of the vital
      status on December 31(st), 2008. Using Cox proportional hazards regression we
      estimated the risk of the SNPs in relation to mortality, adjusting for gender,
      age, FEV1, height, place of residence and packyears of smoking. Additionally, we
      performed stratified analyses according to gender and smoking habits. After 18
      years, 284 (20.4%) subjects had died (107 due to cardiovascular disease and 20
      due to COPD). Individuals homozygous for the minor allele of SNP T_2 had an
      increased risk of all-cause and cardiovascular mortality compared to wild types:
      hazard ratio 3.6 (95% confidence interval 2.0 to 6.7) and 3.4 (1.2 to 9.5)
      respectively. Individuals homozygous for the minor allele of S_1, S_2, T_2 or Q_1
      had a significantly increased risk of COPD mortality. In stratified analyses the
      risk of all-cause mortality associated with SNP T_2 did not change: females 3.5
      (1.5 to 8.3), males 3.1 (1.2 to 7.6), never smokers 3.8 (0.9 to 16.3), ever
      smokers 3.6 (1.8 to 7.2). This study shows for the first time that ADAM33 is a
      pleiotropic gene that is associated with all-cause, COPD and cardiovascular
      mortality, independent of potential confounders. 

PMID- 23861801
TI  - Attenuation of kruppel-like factor 4 facilitates carcinogenesis by inducing g1/s
      phase arrest in clear cell renal cell carcinoma.
AB  - Kruppel-like factor 4 (KLF4) is a transcription factor with diverse functions in
      various cancer types; however, the function of KLF4 in clear cell renal cell
      carcinoma (ccRCC) carcinogenesis remains unknown. In this study, we initially
      examined KLF4 expression by using a cohort of surgically removed ccRCC specimens
      and cell lines. Results indicated that the transcription and translation of KLF4
      were lower in ccRCC tissues than in patient-matched normal tissues. Furthermore,
      the KLF4 expression was significantly downregulated in the five ccRCC cell lines
      at protein and mRNA levels compared with that in normal renal proximal tubular
      epithelial cell lines (HKC). KLF4 downregulation was significantly correlated
      with tumor stage and tumor diameter. Promoter hypermethylation may contribute to
      its low expression. In addition, in vitro studies indicated that the KLF4
      overexpression significantly inhibited proliferation in human ccRCC cell lines
      786-O and ACHN. Moreover, the KLF4 overexpression arrested the cell cycle
      progress at the G1/S phase transition by upregulating p21 (WAF1/CIP1) expression
      and downregulating cyclin D1 expression, KLF4 knockdown in HKC cells did the
      opposite. In vivo studies confirmed the anti-proliferative effect of KLF4. Our
      results suggested that KLF4 had an important function in suppressing the growth
      of ccRCC. 

PMID- 23861803
TI  - Neuroprotective activity of peripherally administered liver growth factor in a
      rat model of Parkinson's disease.
AB  - Liver growth factor (LGF) is a hepatic mitogen purified some years ago that
      promotes proliferation of different cell types and the regeneration of damaged
      tissues, including brain tissue. Considering the possibility that LGF could be
      used as a therapeutic agent in Parkinson's disease, we analyzed its potential
      neuroregenerative and/or neuroprotective activity when peripherally administered
      to unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. For these studies, rats
      subjected to nigrostriatal lesions were treated intraperitoneally twice a week
      with LGF (5 microg/rat) for 3 weeks. Animals were sacrificed 4 weeks after the
      last LGF treatment. The results show that LGF stimulates sprouting of tyrosine
      hydroxylase-positive terminals and increases tyrosine hydroxylase and dopamine
      transporter expression, as well as dopamine levels in the denervated striatum of
      6-OHDA-lesioned rats. In this structure, LGF activates microglia and raises tumor
      necrosis factor-alpha protein levels, which have been reported to have a role in
      neuroregeneration and neuroprotection. Besides, LGF stimulates the
      phosphorylation of MAPK/ERK1/2 and CREB, and regulates the expression of proteins
      which are critical for cell survival such as Bcl2 and Akt. Because LGF partially
      protects dopamine neurons from 6-OHDA neurotoxicity in the substantia nigra, and
      reduces motor deficits in these animals, we propose LGF as a novel factor that
      may be useful in the treatment of Parkinson's disease. 

PMID- 23861804
TI  - Proteomic profiling of rabbit embryonic stem cells derived from parthenotes and
      fertilized embryos.
AB  - Rabbit embryonic stem (rES) cells can be derived from various sources of embryos.
      However, understanding of the gene expression profile, which distincts embryonic
      stem (ES) cells from other cell types, is still extremely limited. In this study,
      we compared the protein profiles of three independent lines of rabbit cells,
      i.e., fibroblasts, fertilized embryo-derived stem (f-rES) cells, and parthenote
      derived ES (p-rES) cells. Proteomic analyses were performed using two-dimensional
      gel electrophoresis (2-DE) and mass spectrometry. Collectively, the expression
      levels of 100 out of 284 protein spots differed significantly among these three
      cell types (p<0.05). Of those differentially expressed spots, 91% were identified
      in the protein database and represented 63 distinct proteins. Proteins with known
      identities are mainly localized in the cytoplasmic compartments (48%), nucleus
      (14%), and cytoskeletal machineries (13%). These proteins were majorly involved
      in biological functions of energy and metabolic pathways (25%), cell growth and
      maintenance (25%), signal transduction (14%), and protein metabolisms (10%). When
      protein expression levels among cell types were compared, six proteins associated
      with a variety of cellular activities, including structural constituents of the
      cytoskeleton (tubulins), structural molecule (KRT8), catalytic molecules (alpha
      enolase), receptor complex scaffold (14-3-3 protein sigma), microfilament motor
      proteins (Myosin-9), and heat shock protein (HSP60), were found highly expressed
      in p-rES cells. Two proteins related to HSP activity and structural constituent
      of cytoskeleton in f-rES cells, and one structural molecule activity protein in
      fibroblasts showed significantly higher expression levels (p<0.05). Marker
      protein expressions in f-rES and p-rES cells were further confirmed by Western
      blotting and immunocytochemical staining. This study demonstrated unique
      proteomic profiles of the three rabbit cell types and revealed some novel
      proteins differentially expressed between f-rES and p-rES cells. These analyses
      provide insights into rES cell biology and would invite more in-depth studies
      toward rES cell applications. 

PMID- 23861805
TI  - Genetic variability in markers of HLA-C expression in two diverse South African
      populations.
AB  - An insertion-deletion (indel) polymorphism within the 3' untranslated region
      (UTR) of HLA-C has been shown to be involved in the regulation of HLA-C
      expression. Individuals who carry a deletion at this position exhibit increased
      HLA-C expression, which associates with lower viral set point in HIV-1 infected
      individuals. This 263 indel (rs67384697) is reported to be in strong linkage
      disequilibrium (LD) with a single nucleotide polymorphism (SNP) 35 kilobases
      upstream of HLA-C (-35T/C; rs9264942) in Caucasian individuals, making this SNP a
      potential marker for both HLA-C expression and HIV-1 disease progression. We
      therefore examined genetic variation within the HLA-C 3' UTR of 265 Black and
      Caucasian South Africans by direct sequencing and identified haplotypes
      encompassing the 263 indel and another indel at position 230 in both populations.
      Concomitant evaluation of variability at the -35 SNP revealed this polymorphism
      to be an inappropriate marker for the 263 indel in these populations. These
      findings provide important insights into genetic variability within the
      regulatory regions of HLA-C that have potential implications for our
      understanding of the regulation of HLA-C expression and its impact on HIV-1
      disease progression. 

PMID- 23861807
TI  - Clinical characteristics of children with autism spectrum disorder and co
      occurring epilepsy.
AB  - OBJECTIVES: To estimate the prevalence of epilepsy in children with Autism
      Spectrum Disorder (ASD) and to determine the demographic and clinical
      characteristics of children with ASD and epilepsy in a large patient population.
      METHODS: Cross-sectional study using four samples of children with ASD for a
      total of 5,815 participants with ASD. The prevalence of epilepsy was estimated
      from a population-based sample. Children with and without epilepsy were compared
      on demographic and clinical characteristics. Multivariate logistic regression was
      used to examine the association between demographic and clinical characteristics
      and epilepsy. RESULTS: The average prevalence of epilepsy in children with ASD 2
      17 years was 12.5%; among children aged 13 years and older, 26% had epilepsy.
      Epilepsy was associated with older age, lower cognitive ability, poorer adaptive
      and language functioning, a history of developmental regression and more severe
      ASD symptoms. The association between epilepsy and the majority of these
      characteristics appears to be driven by the lower IQ of participants with
      epilepsy. In a multivariate regression model, only age and cognitive ability were
      independently associated with epilepsy. Children age 10 or older had 2.35 times
      the odds of being diagnosed with epilepsy (p<.001) and for a one standard
      deviation increase in IQ, the odds of having epilepsy decreased by 47% (p<.001).
      CONCLUSION: This is among the largest studies to date of patients with ASD and co
      occurring epilepsy. Based on a representative sample of children with ASD, the
      average prevalence of epilepsy is approximately 12% and reaches 26% by
      adolescence. Independent associations were found between epilepsy and older age
      and lower cognitive ability. Other risk factors, such as poor language and
      developmental regression, are not associated with epilepsy after controlling for
      IQ. These findings can help guide prognosis and alert clinicians to patients with
      ASD who are at increased risk for epilepsy.

PMID- 23861808
TI  - Evaluating potential spectral impacts of various artificial lights on melatonin
      suppression, photosynthesis, and star visibility.
AB  - Artificial light at night can be harmful to the environment, and interferes with
      fauna and flora, star visibility, and human health. To estimate the relative
      impact of a lighting device, its radiant power, angular photometry and detailed
      spectral power distribution have to be considered. In this paper we focus on the
      spectral power distribution. While specific spectral characteristics can be
      considered harmful during the night, they can be considered advantageous during
      the day. As an example, while blue-rich Metal Halide lamps can be problematic for
      human health, star visibility and vegetation photosynthesis during the night,
      they can be highly appropriate during the day for plant growth and light therapy.
      In this paper we propose three new indices to characterize lamp spectra. These
      indices have been designed to allow a quick estimation of the potential impact of
      a lamp spectrum on melatonin suppression, photosynthesis, and star visibility. We
      used these new indices to compare various lighting technologies objectively. We
      also considered the transformation of such indices according to the propagation
      of light into the atmosphere as a function of distance to the observer. Among
      other results, we found that low pressure sodium, phosphor-converted amber light
      emitting diodes (LED) and LED 2700 K lamps filtered with the new Ledtech's
      Equilib filter showed a lower or equivalent potential impact on melatonin
      suppression and star visibility in comparison to high pressure sodium lamps. Low
      pressure sodium, LED 5000 K-filtered and LED 2700 K-filtered lamps had a lower
      impact on photosynthesis than did high pressure sodium lamps. Finally, we propose
      these indices as new standards for the lighting industry to be used in
      characterizing their lighting technologies. We hope that their use will favor the
      design of new environmentally and health-friendly lighting technologies. 

PMID- 23861806
TI  - Notch and PKC are involved in formation of the lateral region of the dorso
      ventral axis in Drosophila embryos.
AB  - The Notch gene encodes an evolutionarily conserved cell surface receptor that
      generates regulatory signals based on interactions between neighboring cells. In
      Drosophila embryos it is normally expressed at a low level due to strong negative
      regulation. When this negative regulation is abrogated neurogenesis in the
      ventral region is suppressed, the development of lateral epidermis is severely
      disrupted, and the dorsal aminoserosa is expanded. Of these phenotypes only the
      anti-neurogenic phenotype could be linked to excess canonical Notch signaling.
      The other phenotypes were linked to high levels of Notch protein expression at
      the surface of cells in the lateral regions indicating that a non-canonical Notch
      signaling activity normally functions in these regions. Results of our studies
      reported here provide evidence. They show that Notch activities are inextricably
      linked to that of Pkc98E, the homolog of mammalian PKCdelta. Notch and Pkc98E up
      regulate the levels of the phosphorylated form of IkappaBCactus, a negative
      regulator of Toll signaling, and Mothers against dpp (MAD), an effector of Dpp
      signaling. Our data suggest that in the lateral regions of the Drosophila embryos
      Notch activity, in conjunction with Pkc98E activity, is used to form the slopes
      of the opposing gradients of Toll and Dpp signaling that specify cell fates along
      the dorso-ventral axis. 

PMID- 23861809
TI  - Frequency and risk factors for under- and over-treatment in stroke prevention for
      patients with non-valvular atrial fibrillation in general practice.
AB  - OBJECTIVE: To determine adequacy of antithrombotic treatment in patients with non
      valvular atrial fibrillation. To determine risk factors for under- and over
      treatment. DESIGN: Retrospective, cross-sectional study of electronic health
      records from 36 general practitioners in 2008. SETTING: General practice in the
      Netherlands. SUBJECTS: Primary care physicians (n = 36) and patients (n = 981)
      aged 65 years and over. MAIN OUTCOME MEASURES: Rates of adequate, under and over
      treatment, risk factors for under and over-treatment. RESULTS: Of the 981
      included patients with a mean of age 78, 18% received no antithrombotic treatment
      (under-treatment), 13% received antiplatelet drugs and 69% received oral
      anticoagulation (OAC). Further, 43% of the included patients were treated
      adequately, 26% were under-treated, and 31% were over-treated. Patients with a
      previous ischaemic stroke were at high risk for under-treatment (OR 2.4, CI 1.6
      3.5), whereas those with contraindications for OAC were at high risk for over
      treatment (OR 37.0, CI 18.1-79.9). Age over 75 (OR 0.2, CI: 0.1-0.3]), diabetes
      (OR 0.1, CI: 0.1-0.3), heart failure (OR 0.2, CI: 0.1-0.3), hypertension (OR 0.1,
      CI: 0.1-0.2) and previous ischaemic stroke (OR 0.04, CI: 0.02-0.11) protected
      against over-treatment. CONCLUSIONS: In general practice, CHADS2-criteria are
      being used, but the antithrombotic treatment of patients with atrial fibrillation
      frequently deviates from guidelines on this topic. Patients with previous stroke
      are at high risk of not being prescribed OAC. Contraindications for OAC, however,
      seem to be frequently overlooked.

PMID- 23861810
TI  - Refeeding-induced brown adipose tissue glycogen hyper-accumulation in mice is
      mediated by insulin and catecholamines.
AB  - Brown adipose tissue (BAT) generates heat during adaptive thermogenesis through a
      combination of oxidative metabolism and uncoupling protein 1-mediated electron
      transport chain uncoupling, using both free-fatty acids and glucose as substrate.
      Previous rat-based work in 1942 showed that prolonged partial fasting followed by
      refeeding led to a dramatic, transient increase in glycogen stores in multiple
      fat depots. In the present study, the protocol was replicated in male CD1 mice,
      resulting in a 2000-fold increase in interscapular BAT (IBAT) glycogen levels
      within 4-12 hours (hr) of refeeding, with IBAT glycogen stores reaching levels
      comparable to fed liver glycogen. Lesser effects occurred in white adipose
      tissues (WAT). Over the next 36 hr, glycogen levels dissipated and histological
      analysis revealed an over-accumulation of lipid droplets, suggesting a potential
      metabolic connection between glycogenolysis and lipid synthesis. 24 hr of total
      starvation followed by refeeding induced a robust and consistent glycogen over
      accumulation similar in magnitude and time course to the prolonged partial fast.
      Experimentation demonstrated that hyperglycemia was not sufficient to drive
      glycogen accumulation in IBAT, but that elevated circulating insulin was
      sufficient. Additionally, pharmacological inhibition of catecholamine production
      reduced refeeding-induced IBAT glycogen storage, providing evidence of a
      contribution from the central nervous system. These findings highlight IBAT as a
      tissue that integrates both canonically-anabolic and catabolic stimulation for
      the promotion of glycogen storage during recovery from caloric deficit. The
      preservation of this robust response through many generations of animals not
      subjected to food deprivation suggests that the over-accumulation phenomenon
      plays a critical role in IBAT physiology. 

PMID- 23861811
TI  - Wnt pathway activity in breast cancer sub-types and stem-like cells.
AB  - INTRODUCTION: Wnt signalling has been implicated in stem cell regulation however
      its role in breast cancer stem cell regulation remains unclear. METHODS: We used
      a panel of normal and breast cancer cell lines to assess Wnt pathway gene and
      protein expression, and for the investigation of Wnt signalling within stem cell
      enriched populations, mRNA and protein expression was analysed after the
      selection of anoikis-resistant cells. Finally, cell lines and patient-derived
      samples were used to investigate Wnt pathway effects on stem cell activity in
      vitro. RESULTS: Wnt pathway signalling increased in cancer compared to normal
      breast and in both cell lines and patient samples, expression of Wnt pathway
      genes correlated with estrogen receptor (ER) expression. Furthermore, specific
      Wnt pathway genes were predictive for recurrence within subtypes of breast
      cancer. Canonical Wnt pathway genes were increased in breast cancer stem cell
      enriched populations in comparison to normal breast stem cell-enriched
      populations. Furthermore in cell lines, the ligand Wnt3a increased whilst the
      inhibitor DKK1 reduced mammosphere formation with the greatest inhibitory effects
      observed in ER+ve breast cancer cell lines. In patient-derived metastatic breast
      cancer samples, only ER-ve mammospheres were responsive to the ligand Wnt3a.
      However, the inhibitor DKK1 efficiently inhibited both ER+ve and ER-ve breast
      cancer but not normal mammosphere formation, suggesting that the Wnt pathway is
      aberrantly activated in breast cancer mammospheres. CONCLUSIONS: Collectively,
      these data highlight differential Wnt signalling in breast cancer subtypes and
      activity in patient-derived metastatic cancer stem-like cells indicating a
      potential for Wnt-targeted treatment in breast cancers.

PMID- 23861812
TI  - Kidney transplantation is associated with catastrophic out of pocket expenditure
      in India.
AB  - Kidney transplantation (KT) is only viable renal replacement option for most
      patients in India. Most patients do not have health insurance and meet treatment
      expenditure from their own resources. We prospectively evaluated the expenses
      associated with KT and its impact on the socioeconomic status of families in a
      public hospital. All direct and indirect expenses incurred by the patients from
      the time of diagnosis of chronic kidney disease to KT were recorded. Direct
      expenses included physician fees, cost of drugs and disposables, dialysis, and
      expenses on investigations and hospitalization. Indirect expenses included
      travel, food, stay, and loss of income suffered by the family. Educational
      dropout and financial loss were also recorded. There were 43 males and 7 females
      between the ages of 12 and 57 years. Direct expenses ranged from US$ 2,151-23,792
      and accounted for two-thirds of the total expenses. Pre-referral hospitalization,
      dialysis and medication accounted for majority of direct expense. Indirect
      expenses ranged from US$ 226-15,283. Travel expenses and loss of income accounted
      for most of indirect expense. About 54%, 8%, and 10% of families suffered from
      severe, moderate, and some financial crisis respectively. A total of 38 families
      had job losses, and 1 patient and 12 caregivers dropped out of studies. To
      conclude, KT is associated with catastrophic out-of-pocket expenditure and pushes
      a majority of the patients who come for treatment to public hospitals into severe
      financial crisis. Educational dropout and loss of jobs are other major concerns.
      Systematic efforts are required to address these issues. 

PMID- 23861813
TI  - DAT1 polymorphism determines L-DOPA effects on learning about others'
      prosociality.
AB  - Despite that a wealth of evidence links striatal dopamine to individuals reward
      learning performance in non-social environments, the neurochemical underpinnings
      of such learning during social interaction are unknown. Here, we show that the
      administration of 300 mg of the dopamine precursor L-DOPA to 200 healthy male
      subjects influences learning about a partners' prosocial preferences in a novel
      social interaction task, which is akin to a repeated trust game. We found
      learning to be modulated by a well-established genetic marker of striatal
      dopamine levels, the 40-bp variable number tandem repeats polymorphism of the
      dopamine transporter (DAT1 polymorphism). In particular, we found that L-DOPA
      improves learning in 10/10R genoype subjects, who are assumed to have lower
      endogenous striatal dopamine levels and impairs learning in 9/10R genotype
      subjects, who are assumed to have higher endogenous dopamine levels. These
      findings provide first evidence for a critical role of dopamine in learning
      whether an interaction partner has a prosocial or a selfish personality. The
      applied pharmacogenetic approach may open doors to new ways of studying
      psychiatric disorders such as psychosis, which is characterized by distorted
      perceptions of others' prosocial attitudes. 

PMID- 23861814
TI  - SmeltCam: underwater video codend for trawled nets with an application to the
      distribution of the imperiled delta smelt.
AB  - Studying rare and sensitive species is a challenge in conservation biology. The
      problem is exemplified by the case of the imperiled delta smelt Hypomesus
      transpacificus, a small delicate fish species endemic to the San Francisco
      Estuary, California. Persistent record-low levels of abundance and relatively
      high sensitivity to handling stress pose considerable challenges to studying
      delta smelt in the wild. To attempt to overcome these and other challenges we
      have developed the SmeltCam, an underwater video camera codend for trawled nets.
      The SmeltCam functions as an open-ended codend that automatically collects
      information on the number and species of fishes that pass freely through a
      trawled net without handling. We applied the SmeltCam to study the fine-scale
      distribution of juvenile delta smelt in the water column in the upper San
      Francisco Estuary. We learned that during flood tides delta smelt were relatively
      abundant throughout the water column and that during ebb tides delta smelt were
      significantly less abundant and occurred only in the lower half and sides of the
      water column. The results suggest that delta smelt manipulate their position in
      the water column to facilitate retention in favorable habitats. With the
      application of the SmeltCam we increased the survival of individual delta smelt
      by 72% compared to using a traditional codend, where all of the fish would have
      likely died due to handling stress. The SmeltCam improves upon similar previously
      developed silhouette photography or video recording devices and demonstrates how
      new technology can be developed to address important questions in conservation
      biology as well as lessen the negative effects associated with traditional
      sampling methods on imperiled species. 

PMID- 23861815
TI  - Kinetic features of L,D-transpeptidase inactivation critical for beta-lactam
      antibacterial activity.
AB  - Active-site serine D,D-transpeptidases belonging to the penicillin-binding
      protein family (PBPs) have been considered for a long time as essential for
      peptidoglycan cross-linking in all bacteria. However, bypass of the PBPs by an
      L,D-transpeptidase (Ldt(fm)) conveys high-level resistance to beta-lactams of the
      penam class in Enterococcus faecium with a minimal inhibitory concentration (MIC)
      of ampicillin >2,000 ug/ml. Unexpectedly, Ldt(fm) does not confer resistance to
      beta-lactams of the carbapenem class (imipenem MIC = 0.5 ug/ml) whereas cephems
      display residual activity (ceftriaxone MIC = 128 ug/ml). Mass spectrometry,
      fluorescence kinetics, and NMR chemical shift perturbation experiments were
      performed to explore the basis for this specificity and identify beta-lactam
      features that are critical for efficient L,D-transpeptidase inactivation. We show
      that imipenem, ceftriaxone, and ampicillin acylate Ldt(fm) by formation of a
      thioester bond between the active-site cysteine and the beta-lactam-ring
      carbonyl. However, slow acylation and slow acylenzyme hydrolysis resulted in
      partial Ldt(fm) inactivation by ampicillin and ceftriaxone. For ampicillin,
      Ldt(fm) acylation was followed by rupture of the C(5)-C(6) bond of the beta
      lactam ring and formation of a secondary acylenzyme prone to hydrolysis. The
      saturable step of the catalytic cycle was the reversible formation of a
      tetrahedral intermediate (oxyanion) without significant accumulation of a non
      covalent complex. In agreement, a derivative of Ldt(fm) blocked in acylation
      bound ertapenem (a carbapenem), ceftriaxone, and ampicillin with similar low
      affinities. Thus, oxyanion and acylenzyme stabilization are both critical for
      rapid L,D-transpeptidase inactivation and antibacterial activity. These results
      pave the way for optimization of the beta-lactam scaffold for L,D-transpeptidase
      inactivation.

PMID- 23861816
TI  - Progressive levels of physical dependence to tobacco coincide with changes in the
      anterior cingulum bundle microstructure.
AB  - BACKGROUND: The tobacco withdrawal syndrome indicates the development of
      neurophysiologic dependence. Clinical evidence indicates that neurophysiologic
      dependence develops through a set sequence of symptom presentation that can be
      assessed with a new 3-item survey measure of wanting, craving, and needing
      tobacco, the Level of Physical Dependence (PD). This study sought to determine if
      advancing neurophysiologic dependence as measured by the Level of PD correlates
      with characteristics of white matter structure measured by Fractional Anisotropy
      (FA). METHODS: Diffusion-MRI based FA and diffusion tensor imaging probabilistic
      tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also
      examined in relation to two additional measures of dependence severity, the
      Hooked on Nicotine Checklist (HONC), and the Fagerstrom Test for Nicotine
      Dependence (FTND). RESULTS: Among smokers, FA in the left anterior cingulate
      bundle (ACb) correlated negatively with the Level of PD (r = -0.68, p = 0.02) and
      HONC scores (r = -0.65, p = 0.03), but the correlation for the FTND did not reach
      statistical significance (r = -49, p = 0.12). With advancing Levels of PD, the
      density of streamlines between the ACb and precuneus increased (r = -0.67,
      p<0.05) and those between the ACb and white matter projecting to the superior
      frontal cortex (r = -0.86, p = 0.0006) decreased significantly. CONCLUSIONS: The
      correlations between neural structure and both the clinical Level of PD survey
      measure and the HONC suggest that the Level of PD and the HONC may reflect the
      microstructural integrity of white matter, as influenced by tobacco abuse. Given
      that the Level of PD is measuring a sequence of symptoms of neurophysiologic
      dependence that develops over time, the correlation between the Level of PD and
      neural structure suggests that these features might represent neuroplastic
      changes that develop over time to support the development of neurophysiologic
      dependence.

PMID- 23861817
TI  - High levels of DegU-P activate an Esat-6-like secretion system in Bacillus
      subtilis.
AB  - The recently discovered Type VII/Esat-6 secretion systems seem to be widespread
      among bacteria of the phyla Actinobacteria and Firmicutes. In some species they
      play an important role in pathogenic interactions with eukaryotic hosts. Several
      studies have predicted that the locus yukEDCByueBC of the non-pathogenic, Gram
      positive bacterium Bacillus subtilis would encode an Esat-6-like secretion system
      (Ess). We provide here for the first time evidences for the functioning of this
      secretion pathway in an undomesticated B. subtilis strain. We show that YukE, a
      small protein with the typical features of the secretion substrates from the
      WXG100 superfamily is actively secreted to culture media. YukE secretion depends
      on intact yukDCByueBC genes, whose products share sequence or structural homology
      with known components of the S. aureus Ess. Biochemical characterization of YukE
      indicates that it exists as a dimer both in vitro and in vivo. We also show that
      the B. subtilis Ess essentially operates in late stationary growth phase in
      absolute dependence of phosphorylated DegU, the response regulator of the two
      component system DegS-DegU. We present possible reasons that eventually have
      precluded the study of this secretion system in the B. subtilis laboratory strain
      168. 

PMID- 23861818
TI  - Killer immunoglobulin-like receptor (KIR) centromeric-AA haplotype is associated
      with ethnicity and tuberculosis disease in a Canadian First Nations cohort.
AB  - Killer immunoglobulin-like receptors (KIR) on natural killer (NK) cells interact
      with other immune cells to monitor the immune system and combat infectious
      diseases, such as tuberculosis (TB). The balance of activating and inhibiting KIR
      interactions helps determine the NK cell response. In order to examine the
      enrichment or depletion of KIRs as well as to explore the association between TB
      status and inhibitory/stimulatory KIR haplotypes, we performed KIR genotyping on
      samples from 93 Canadian First Nations (Dene, Cree, and Ojibwa) individuals from
      Manitoba with active, latent, or no TB infection, and 75 uninfected Caucasian
      controls. There were significant differences in KIR genes between Caucasians and
      First Nations samples and also between the First Nations ethnocultural groups
      (Dene, Cree, and Ojibwa). When analyzing ethnicity and tuberculosis status in the
      study population, it appears that the KIR profile and centromeric haplotype are
      more predictive than the presence or absence of individual genes. Specifically,
      the decreased presence of haplotype B centromeric genes and increased presence of
      centromeric-AA haplotypes in First Nations may contribute to an inhibitory immune
      profile, explaining the high rates of TB in this population. 

PMID- 23861819
TI  - Three-dimensional structure of human NLRP10/PYNOD pyrin domain reveals a
      homotypic interaction site distinct from its mouse homologue.
AB  - NLRPs (Nucleotide-binding domain, leucine-rich repeat and pyrin domain containing
      proteins) are a family of pattern-recognition receptors (PRRs) that sense
      intracellular microbial components and endogenous stress signals. NLRP10 (also
      known as PYNOD) is a unique NLRP member characterized by a lack of the putative
      ligand-binding leucine-rich repeat domain. Recently, human NLRP10 has been shown
      to inhibit the self-association of ASC into aggregates and ASC-mediated
      procaspase-1 processing. However, such activities are not found in mouse NLRP10.
      Here we report the solution structure and dynamics of human NLRP10 pyrin domain
      (PYD), whose helix H3 and loop H2-H3 adopt a conformation distinct from those of
      mouse NLRP10. Docking studies show that human and mouse NLRP10 PYDs may interact
      differently with ASC PYD. These results provide a possible structural explanation
      for the contrasting effect of NLRP10 on ASC aggregation in human cells versus
      mouse models. Finally, we also provide evidence that in human NLRP10 the PYD
      domain may not interact with the NOD domain to regulate its intrinsic nucleotide
      hydrolysis activity. 

PMID- 23861820
TI  - Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS
      induced tumorigenesis.
AB  - Selenium (Se) is an essential micronutrient that exerts its functions via
      selenoproteins. Little is known about the role of Se in inflammatory bowel
      disease (IBD). Epidemiological studies have inversely correlated nutritional Se
      status with IBD severity and colon cancer risk. Moreover, molecular studies have
      revealed that Se deficiency activates WNT signaling, a pathway essential to
      intestinal stem cell programs and pivotal to injury recovery processes in IBD
      that is also activated in inflammatory neoplastic transformation. In order to
      better understand the role of Se in epithelial injury and tumorigenesis resulting
      from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or 
      sufficient mice in response to dextran sodium sulfate (DSS)-induced colitis, and
      azoxymethane (AOM) followed by cyclical administration of DSS, respectively. In
      response to DSS alone, Se-deficient mice demonstrated increased morbidity, weight
      loss, stool scores, and colonic injury with a concomitant increase in DNA damage
      and increases in inflammation-related cytokines. As there was an increase in DNA
      damage as well as expression of several EGF and TGF-beta pathway genes in
      response to inflammatory injury, we sought to determine if tumorigenesis was
      altered in the setting of inflammatory carcinogenesis. Se-deficient mice
      subjected to AOM/DSS treatment to model colitis-associated cancer (CAC) had
      increased tumor number, though not size, as well as increased incidence of high
      grade dysplasia. This increase in tumor initiation was likely due to a general
      increase in colonic DNA damage, as increased 8-OHdG staining was seen in Se
      deficient tumors and adjacent, non-tumor mucosa. Taken together, our results
      indicate that Se deficiency worsens experimental colitis and promotes tumor
      development and progression in inflammatory carcinogenesis. 

PMID- 23861821
TI  - MicroRNA-196b regulates the homeobox B7-vascular endothelial growth factor axis
      in cervical cancer.
AB  - The down-regulation of microRNA-196b (miR-196b) has been reported, but its
      contribution to cervical cancer progression remains to be investigated. In this
      study, we first demonstrated that miR-196b down-regulation was significantly
      associated with worse disease-free survival (DFS) for cervical cancer patients
      treated with combined chemo-radiation. Secondly, using a tri-modal approach for
      target identification, we determined that homeobox-B7 (HOXB7) was a bona fide
      target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a
      downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression
      by transient transfection resulted in reduced cell growth, clonogenicity,
      migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor
      cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF
      phenocopied the biological effects of miR-196b over-expression. Our findings have
      demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in
      cervical cancer progression; hence targeting this pathway could be a promising
      therapeutic strategy for the future management of this disease. 

PMID- 23861822
TI  - A novel missense (M206K) STAT3 mutation in diffuse large B cell lymphoma
      deregulates STAT3 signaling.
AB  - Persistent STAT3 activation has been found in activated B-cell like diffuse large
      B cell tumors (DLBCL). To investigate whether genetic mutations play a role in
      aberrant STAT3 signaling in DLBCL, we bi-directionally sequenced all 24 exons of
      the STAT3 gene in DLBCL tumors (n = 40). We identified 2 novel point mutations in
      2 separate (2/40; 5%) patients at exon 7 and 24. Point mutation 2552G>A was a
      silent mutation in the stop codon. Another heterozygous mutation 857T>A encoded a
      methionine substitution by lysine at codon 206 (M206K) in the coiled-coil domain
      of STAT3. We performed site directed mutagenesis to mutate wild type (WT)
      STAT3alpha and STAT3beta at codon 206 and constructed stable cell lines by
      lentiviral transfection of STAT3alpha(WT), STAT3alpha(M206K), STAT3beta(WT) and
      STAT3beta(M206K) plasmids. The mutation was found to increase STAT3
      phosphorylation in STAT3alpha mutant cell lines with no effect on the STAT3beta
      mutant cell line. Transcriptional activation was also increased in the STAT3alpha
      mutant cells compared with STAT3alpha WT cells as detected by a luciferase
      reporter assay. Moreover, STAT3alpha(M206K) mutant cells were resistant to JAK2
      pathway inhibition compared to STAT3alpha WT cells. These results indicate that
      missense mutations in STAT3 increase signaling through the JAK/STAT pathway. JAK2
      inhibitors may be useful in the patient with this STAT3 mutation as well as those
      with pathway activation by other mechanisms. 

PMID- 23861823
TI  - The suitability of P. falciparum merozoite surface proteins 1 and 2 as genetic
      markers for in vivo drug trials in Yemen.
AB  - BACKGROUND: The accuracy of the conclusions from in vivo efficacy anti-malarial
      drug trials depends on distinguishing between recrudescences and re-infections
      which is accomplished by genotyping genes coding P. falciparum merozoite surface
      1 (MSP1) and MSP2. However, the reliability of the PCR analysis depends on the
      genetic markers' allelic diversity and variant frequency. In this study the
      genetic diversity of the genes coding for MSP1 and MSP2 was obtained for P.
      falciparum parasites circulating in Yemen. METHODS: Blood samples were collected
      from 511 patients with fever and screened for malaria parasites using Giemsa
      stained blood films. A total 74 samples were infected with P. falciparum, and the
      genetic diversity was assessed by nested PCR targeting Pfmsp1 (Block2) and Pfmsp2
      (block 3). RESULTS: Overall, 58%, 28% and 54% of the isolates harboured parasites
      of the Pfmsp1 K1, MAD20 and RO33 allelic families, and 55% and 89% harboured
      those of the Pfmsp2 FC27 and 3D7 allelic families, respectively. For both genetic
      makers, the multiplicity of the infection (MOI) was significantly higher in the
      isolates from the foothills/coastland areas as compared to those from the
      highland (P<0.05). Pfmsp2 had higher number of distinct allelic variants than
      Pfmsp1 (20 vs 11). The expected heterozygosity (HE) for Pfmsp1 and Pfmsp2 were
      0.82 and 0.94, respectively. Nonetheless, a bias in the frequency distribution of
      the Pfmsp1 allelic variants was noted from all areas, and of those of Pfmsp2 in
      the samples collected from the highland areas. CONCLUSIONS: Significant
      differences in the complexity and allelic diversity of Pfmsp1 and Pfmsp2 genes
      between areas probably reflect differences in the intensity of malaria
      transmission. The biased distribution of allelic variants suggests that in Yemen
      Pfmsp1 should not be used for PCR correction of in vivo clinical trials outcomes,
      and that caution should be exercised when employing Pfmsp2.

PMID- 23861824
TI  - Strategies to optimize participation in diabetes prevention programs following
      gestational diabetes: a focus group study.
AB  - OBJECTIVE: We performed a qualitative study among women within 5 years of
      Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements
      that would enhance participation in a type 2 diabetes (DM2) prevention program.
      RESEARCH DESIGN AND METHODS: Potential participants received up to three
      invitation letters from their GDM physician. Four focus groups were held.
      Discussants were invited to comment on potential facilitators/barriers to
      participation and were probed on attitudes towards meal replacement and
      Internet/social media tools. Recurring themes were identified through qualitative
      content analysis of discussion transcripts. RESULTS: Among the 1,201 contacted
      and 79 eligible/interested, 29 women attended a focus group discussion. More than
      half of discussants were overweight/obese, and less than half were physically
      active. For DM2 prevention, a strong need for social support to achieve changes
      in dietary and physical activity habits was expressed. In this regard, face-to
      face interactions with peers and professionals were preferred, with adjunctive
      roles for Internet/social media. Further, direct participation of
      partners/spouses in a DM2 prevention program was viewed as important to enhance
      support for behavioural change at home. Discussants highlighted work and child
      related responsibilities as potential barriers to participation, and emphasized
      the importance of childcare support to allow attendance. Meal replacements were
      viewed with little interest, with concerns that their use would provide a poor
      example of eating behaviour to children. CONCLUSIONS: Among women within 5 years
      of a GDM diagnosis who participated in a focus group discussion, participation in
      a DM2 prevention program would be enhanced by face-to-face interactions with
      professionals and peers, provision of childcare support, and inclusion of
      spouses/partners.

PMID- 23861825
TI  - Grain amaranths are defoliation tolerant crop species capable of utilizing stem
      and root carbohydrate reserves to sustain vegetative and reproductive growth
      after leaf loss.
AB  - Tolerance to defoliation can be defined as the degree to which productivity is
      affected by photosynthetic area reduction. This trait was studied in grain
      amaranth (Amaranthus cruentus and A. hypochondriacus), which are considered to be
      a highly defoliation-tolerant species. The physiological and biochemical
      responses to increasing levels of mechanical leaf removal up to total defoliation
      were quantified. Tolerance appeared to be dependent on various factors: ( i)
      amount of lost tissue; (ii) mechanics of leaf tissue removal; (iii) environment,
      and (iv) species tested. Thus, grain amaranth was found to be a highly tolerant
      species under green-house conditions when leaf tissue loss was performed by
      gradual perforation. However, tolerance was compromised under similar conditions
      when defoliation was done by gradual cutting of the leaf. Also tolerance in
      completely defoliated plants tended to decrease under field conditions, where
      differences between A. cruentus and A. hypochondriacus were observed. All non
      structural carbohydrate (NSC) levels were reduced in stems and roots of totally
      defoliated amaranths one day after treatment. Such depletion probably provided
      the carbon (C) resources needed to sustain the early recovery process in the
      absence of photosynthetic capacity. This was corroborated by shading of intact
      plants, which produced the same rapid and drastic reduction of NSC levels in
      these tissues. These results emphasize the role of stored NSCs, particularly
      starch, in buffering the impact of severe defoliation in amaranth. The fall in
      sucrose synthase and cell wall invertase activity observed in stems and roots
      soon after defoliation was consistent with their predicted shift from sink to
      source tissues. It is concluded that mobilization of C stores in stems and roots,
      is a physiologically important trait underlying tolerance to defoliation in grain
      amaranth. 

PMID- 23861827
TI  - Automated UMLS-based comparison of medical forms.
AB  - Medical forms are very heterogeneous: on a European scale there are thousands of
      data items in several hundred different systems. To enable data exchange for
      clinical care and research purposes there is a need to develop interoperable
      documentation systems with harmonized forms for data capture. A prerequisite in
      this harmonization process is comparison of forms. So far--to our knowledge--an
      automated method for comparison of medical forms is not available. A form
      contains a list of data items with corresponding medical concepts. An automatic
      comparison needs data types, item names and especially item with these unique
      concept codes from medical terminologies. The scope of the proposed method is a
      comparison of these items by comparing their concept codes (coded in UMLS). Each
      data item is represented by item name, concept code and value domain. Two items
      are called identical, if item name, concept code and value domain are the same.
      Two items are called matching, if only concept code and value domain are the
      same. Two items are called similar, if their concept codes are the same, but the
      value domains are different. Based on these definitions an open-source
      implementation for automated comparison of medical forms in ODM format with UMLS
      based semantic annotations was developed. It is available as package compareODM
      from http://cran.r-project.org. To evaluate this method, it was applied to a set
      of 7 real medical forms with 285 data items from a large public ODM repository
      with forms for different medical purposes (research, quality management, routine
      care). Comparison results were visualized with grid images and dendrograms.
      Automated comparison of semantically annotated medical forms is feasible.
      Dendrograms allow a view on clustered similar forms. The approach is scalable for
      a large set of real medical forms.

PMID- 23861826
TI  - Acetic acid activates the AMP-activated protein kinase signaling pathway to
      regulate lipid metabolism in bovine hepatocytes.
AB  - The effect of acetic acid on hepatic lipid metabolism in ruminants differs
      significantly from that in monogastric animals. Therefore, the aim of this study
      was to investigate the regulation mechanism of acetic acid on the hepatic lipid
      metabolism in dairy cows. The AMP-activated protein kinase (AMPK) signaling
      pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine
      hepatocytes were cultured and treated with different concentrations of sodium
      acetate (neutralized acetic acid) and BML-275 (an AMPKalpha inhibitor). Acetic
      acid consumed a large amount of ATP, resulting in an increase in AMPKalpha
      phosphorylation. The increase in AMPKalpha phosphorylation increased the
      expression and transcriptional activity of peroxisome proliferator-activated
      receptor alpha, which upregulated the expression of lipid oxidation genes,
      thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated
      AMPKalpha phosphorylation reduced the expression and transcriptional activity of
      the sterol regulatory element-binding protein 1c and the carbohydrate responsive
      element-binding protein, which reduced the expression of lipogenic genes, thereby
      decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated
      AMPKalpha inhibited the activity of acetyl-CoA carboxylase. Consequently, the
      triglyceride content in the acetate-treated hepatocytes was significantly
      decreased. These results indicate that acetic acid activates the AMPKalpha
      signaling pathway to increase lipid oxidation and decrease lipid synthesis in
      bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows. 

PMID- 23861828
TI  - Thematic and spatial resolutions affect model-based predictions of tree species
      distribution.
AB  - Subjective decisions of thematic and spatial resolutions in characterizing
      environmental heterogeneity may affect the characterizations of spatial pattern
      and the simulation of occurrence and rate of ecological processes, and in turn,
      model-based tree species distribution. Thus, this study quantified the importance
      of thematic and spatial resolutions, and their interaction in predictions of tree
      species distribution (quantified by species abundance). We investigated how model
      predicted species abundances changed and whether tree species with different
      ecological traits (e.g., seed dispersal distance, competitive capacity) had
      different responses to varying thematic and spatial resolutions. We used the
      LANDIS forest landscape model to predict tree species distribution at the
      landscape scale and designed a series of scenarios with different thematic
      (different numbers of land types) and spatial resolutions combinations, and then
      statistically examined the differences of species abundance among these
      scenarios. Results showed that both thematic and spatial resolutions affected
      model-based predictions of species distribution, but thematic resolution had a
      greater effect. Species ecological traits affected the predictions. For species
      with moderate dispersal distance and relatively abundant seed sources, predicted
      abundance increased as thematic resolution increased. However, for species with
      long seeding distance or high shade tolerance, thematic resolution had an inverse
      effect on predicted abundance. When seed sources and dispersal distance were not
      limiting, the predicted species abundance increased with spatial resolution and
      vice versa. Results from this study may provide insights into the choice of
      thematic and spatial resolutions for model-based predictions of tree species
      distribution. 

PMID- 23861829
TI  - Early assessment of the efficacy of temozolomide chemotherapy in experimental
      glioblastoma using [18F]FLT-PET imaging.
AB  - Addition of temozolomide (TMZ) to radiation therapy is the standard treatment for
      patients with glioblastoma (GBM). However, there is uncertainty regarding the
      effectiveness of TMZ. Considering the rapid evolution of the disease, methods to
      assess TMZ efficacy early during treatment would be of great benefit. Our aim was
      to monitor early effects of TMZ in a mouse model of GBM using positron emission
      tomography (PET) with 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT). METHODS:
      Human glioma cells sensitive to TMZ (Gli36dEGFR-1) were treated with sub-lethal
      doses of TMZ to obtain cells with lower sensitivity to TMZ (Gli36dEGFR-2), as
      measured by growth and clonogenic assays. Gli36dEGFR-1 and Gli36dEGFR-2 cells
      were subcutaneously (s.c.) or intracranially (i.c.) xenografted into nude mice.
      Mice were treated for 7 days with daily injection of 25 or 50 mg/kg TMZ.
      Treatment efficacy was measured using [(18)F]FLT-PET before treatment and after 2
      days. Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) were used to
      determine tumor volumes before treatment and after 7 days. RESULTS: A significant
      difference was observed between TMZ and DMSO treated tumors in terms of
      variations of [(18)F]FLT T/B ratio as soon as day 2 in the i.c. as well as in the
      s.c. mouse model. Variations of [(18)F]FLT T/B uptake ratio between days 0 and 2
      correlated with variations of tumor size between days 0 and 7 (s.c. model:
      n(tumor) = 17 in n(mice) = 11, P<0.01; i.c. model: n(tumor/mice) = 9, P<0.01).
      CONCLUSIONS: Our results indicate that [(18)F]FLT-PET may be useful for an early
      evaluation of the response of GBM to TMZ chemotherapy in patients with glioma.

PMID- 23861830
TI  - Regional variations in esophageal cancer rates by census region in the United
      States, 1999-2008.
AB  - BACKGROUND: Assessment of cancer incidence trends within the U.S. have mostly
      relied upon Surveillance, Epidemiology, and End Results (SEER) data, with
      implicit inference that such is representative of the general population.
      However, many cancer policy decisions are based at a more granular level. To help
      inform such, analyses of regional cancer incidence data are needed. Leveraging
      the unique resource of National Program of Cancer Registries (NPCR)-SEER, we
      assessed whether regional rates and trends of esophageal cancer significantly
      deviated from national estimates. METHODS: From NPCR-SEER, we extracted cancer
      case counts and populations for whites aged 45-84 years by calendar year,
      histology, sex, and census region for the period 1999-2008. We calculated age
      standardized incidence rates (ASRs), annual percent changes (APCs), and male-to
      female incidence rate ratios (IRRs). RESULTS: This analysis included 65,823
      esophageal adenocarcinomas and 27,094 esophageal squamous cell carcinomas
      diagnosed during 778 million person-years. We observed significant geographic
      variability in incidence rates and trends, especially for esophageal
      adenocarcinomas in males: ASRs were highest in the Northeast (17.7 per 100,000)
      and Midwest (18.1). Both were significantly higher than the national estimate
      (16.0). In addition, the Northeast APC was 62% higher than the national estimate
      (3.19% vs. 1.97%). Lastly, IRRs remained fairly constant across calendar time,
      despite changes in incidence rates. CONCLUSION: Significant regional variations
      in esophageal cancer incidence trends exist in the U.S. Stable IRRs may indicate
      the predominant factors affecting incidence rates are similar in men and women.

PMID- 23861831
TI  - Females lead population collapse of the endangered Hawaii creeper.
AB  - Population collapses result from drastic environmental changes, but the sexes may
      differ in vulnerability. Collapse of the endangered Hawaii creeper (Oreomystis
      mana) at Hakalau Forest National Wildlife Refuge resulted from food limitation
      associated with increased numbers of an introduced bird (Japanese white-eye,
      Zosterops japonicus), which competes with the creeper for food. Both creeper
      sexes had stunted bill growth and the greatest change in molt of native species
      in the community. With a surge in numbers of white-eyes, a recent cohort of adult
      females had very low survival after breeding, while adult males from the same
      cohort, and older females and males, continued to have high survival. Lower
      female survival resulted in a significantly more male-biased adult sex ratio.
      Recent low female survival was based on a great cost of reproduction, indicated
      by molt-breeding overlap that was previously avoided, and lower fat during the
      lengthy fledgling period. The difference in female survival between cohorts was
      associated with stunted bills from being reared in and then breeding in an
      increasingly poor food environment. Trend analysis of survey data indicate that
      the bird is declining throughout the refuge, with males being 72-80% of adults
      left six years after the white-eye increased. Competition over time was
      consistent with that previously documented over space on the Island of Hawaii.
      Adaptive management to recover the bird in this protected area needs to focus on
      improving both adult female survival and the adult sex ratio. 

PMID- 23861832
TI  - Looking ahead: anticipatory gaze and motor ability in infancy.
AB  - The present study asks when infants are able to selectively anticipate the goals
      of observed actions, and how this ability relates to infants' own abilities to
      produce those specific actions. Using eye-tracking technology to measure on-line
      anticipation, 6-, 8- and 10-month-old infants and a control group of adults were
      tested while observing an adult reach with a whole hand grasp, a precision grasp
      or a closed fist towards one of two different sized objects. The same infants
      were also given a comparable action production task. All infants showed proactive
      gaze to the whole hand grasps, with increased degrees of proactivity in the older
      groups. Gaze proactivity to the precision grasps, however, was present from 8
      months of age. Moreover, the infants' ability in performing precision grasping
      strongly predicted their ability in using the actor's hand shape cues to
      differentially anticipate the goal of the observed action, even when age was
      partialled out. The results are discussed in terms of the specificity of action
      anticipation, and the fine-grained relationship between action production and
      action perception. 

PMID- 23861833
TI  - DNA methylation of alternative promoters directs tissue specific expression of
      Epac2 isoforms.
AB  - Epac 1 and Epac 2 (Epac1/2; exchange factors directly activated by cAMP) are
      multidomain proteins that mediate cellular responses upon activation by the
      signaling molecule cAMP. Epac1 is ubiquitously expressed, whereas Epac2 exhibits
      a restricted expression pattern. The gene encoding Epac2 gives rise to at least
      three protein isoforms (Epac2A, Epac2B and Epac2C) that exhibit confined tissue
      and cell specific expression profiles. Here, we describe alternative promoter
      usage for the different isoforms of Epac2, and demonstrate that the activity of
      these promoters depend on the DNA methylation status. Bisulfite sequencing
      demonstrated that the level of methylation of the promoters in different tissues
      correlates with Epac2 isoform expression. The presented data indicate that the
      tissue-specific expression of the Epac2 isoforms is epigenetically regulated, and
      identify tissue-specific differentially methylated promoter regions within the
      Epac2 locus that are essential for its transcriptional control. 

PMID- 23861834
TI  - Network-based data integration for selecting candidate virulence associated
      proteins in the cereal infecting fungus Fusarium graminearum.
AB  - The identification of virulence genes in plant pathogenic fungi is important for
      understanding the infection process, host range and for developing control
      strategies. The analysis of already verified virulence genes in phytopathogenic
      fungi in the context of integrated functional networks can give clues about the
      underlying mechanisms and pathways directly or indirectly linked to fungal
      pathogenicity and can suggest new candidates for further experimental
      investigation, using a 'guilt by association' approach. Here we study 133 genes
      in the globally important Ascomycete fungus Fusarium graminearum that have been
      experimentally tested for their involvement in virulence. An integrated network
      that combines information from gene co-expression, predicted protein-protein
      interactions and sequence similarity was employed and, using 100 genes known to
      be required for virulence, we found a total of 215 new proteins potentially
      associated with virulence of which 29 are annotated as hypothetical proteins. The
      majority of these potential virulence genes are located in chromosomal regions
      known to have a low recombination frequency. We have also explored the taxonomic
      diversity of these candidates and found 25 sequences, which are likely to be
      fungal specific. We discuss the biological relevance of a few of the potentially
      novel virulence associated genes in detail. The analysis of already verified
      virulence genes in phytopathogenic fungi in the context of integrated functional
      networks can give clues about the underlying mechanisms and pathways directly or
      indirectly linked to fungal pathogenicity and can suggest new candidates for
      further experimental investigation, using a 'guilt by association' approach. 

PMID- 23861835
TI  - Efficacy and safety profile of combining vandetanib with chemotherapy in patients
      with advanced non-small cell lung cancer: a meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy and safety profile of combining vandetanib
      with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).
      METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials
      (CENTRAL), ASCO Abstracts, ESMO Abstracts, Wanfang Database, CNKI were searched.
      Eligible studies were the randomized clinical trials (RCTs) that compared the
      efficacy and safety profile of adding vandetanib to chemotherapy with single
      chemotherapy in patients with advanced NSCLC. The outcomes included overall
      survival (OS), progression-free survival (PFS), overall response rate (ORR) and
      toxicities. All meta-analysis were performed using Review Manager 5.1. The fixed
      effect model weighted by the Mantel-Haenszel method was used. When considerable
      heterogeneity was found (p<0.1, or I(2)>50%), further analysis (subgroup
      analysis, sensitivity analysis or random-effect model) was performed to identify
      potential cause. RESULTS: Results reported from 5 RCTs involving 2284 patients
      were included in the analysis. Compared to chemotherapy alone, the addition of
      vandetanib resulted in a significant longer PFS (HR 0.79 [0.72-0.87], p<0.00001)
      and a higher ORR (RR 1.75 [1.43-2.15], p<0.00001), but failed to show advantage
      on OS (HR 0.96 [0.87-1.06], p = 0.44). CONCLUSION: Vandetanib has activity in
      NSCLC. Identification of predictive biomarkers is warranted in future trials to
      select a subset of patients with advanced NSCLC who may benefit from vandetanib.

PMID- 23861836
TI  - Decreasing fertility rate correlates with the chronological increase and
      geographical variation in incidence of Kawasaki disease in Japan.
AB  - BACKGROUND: Kawasaki disease (KD) is a common cause of acquired paediatric heart
      disease in developed countries. KD was first identified in the 1960s in Japan,
      and has been steadily increasing since it was first reported. The aetiology of KD
      has not been defined, but is assumed to be infection-related. The present study
      sought to identify the factor(s) that mediate the geographical variation and
      chronological increase of KD in Japan. METHODS AND FINDINGS: Based upon data
      reported between 1979 and 2010 from all 47 prefectures in Japan, the incidence
      and mean patient age at the onset of KD were estimated. Using spatial and time
      series analyses, incidence and mean age were regressed against
      climatic/socioeconomic variables. Both incidence and mean age of KD were
      inversely correlated with the total fertility rate (TFR; i.e., the number of
      children that would be born to one woman). The extrapolation of a time-series
      regressive model suggested that KD emerged in the 1960s because of a dramatic
      decrease in TFR in the 1940s through the 1950s. CONCLUSIONS: Mean patient age is
      an inverse surrogate for the hazard of contracting the aetiologic agent.
      Therefore, the observed negative correlation between mean patient age and TFR
      suggests that a higher TFR is associated with KD transmission. This relationship
      may be because a higher TFR facilitates sibling-to-sibling transmission.
      Additionally, the observed inverse correlation between incidence and TFR implies
      a paradoxical "negative" correlation between the incidence and the hazard of
      contracting the aetiologic agent. It was hypothesized that a decreasing TFR
      resulted in a reduced hazard of contracting the agent for KD, thereby increasing
      KD incidence.

PMID- 23861837
TI  - Functional divergence in shrimp anti-lipopolysaccharide factors (ALFs): from
      recognition of cell wall components to antimicrobial activity.
AB  - Antilipopolysaccharide factors (ALFs) have been described as highly cationic
      polypeptides with a broad spectrum of potent antimicrobial activities. In
      addition, ALFs have been shown to recognize LPS, a major component of the Gram
      negative bacteria cell wall, through conserved amino acid residues exposed in the
      four-stranded beta-sheet of their three dimensional structure. In penaeid shrimp,
      ALFs form a diverse family of antimicrobial peptides composed by three main
      variants, classified as ALF Groups A to C. Here, we identified a novel group of
      ALFs in shrimp (Group D ALFs), which corresponds to anionic polypeptides in which
      many residues of the LPS binding site are lacking. Both Group B (cationic) and
      Group D (anionic) shrimp ALFs were produced in a heterologous expression system.
      Group D ALFs were found to have impaired LPS-binding activities and only limited
      antimicrobial activity compared to Group B ALFs. Interestingly, all four ALF
      groups were shown to be simultaneously expressed in an individual shrimp and to
      follow different patterns of gene expression in response to a microbial
      infection. Group B was by far the more expressed of the ALF genes. From our
      results, nucleotide sequence variations in shrimp ALFs result in functional
      divergence, with significant differences in LPS-binding and antimicrobial
      activities. To our knowledge, this is the first functional characterization of
      the sequence diversity found in the ALF family. 

PMID- 23861838
TI  - Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics
      and treatment outcomes: a parallel-group prospective cohort study in two sub
      Saharan Africa populations.
AB  - OBJECTIVES: We evaluated the importance of ethnicity and pharmacogenetic
      variations in determining efavirenz pharmacokinetics, auto-induction and
      immunological outcomes in two African populations. METHODS: ART naive HIV
      patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively
      enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were
      determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz
      and 8-hydroxyefvairenz concentrations were determined at week 4 and 16.
      Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1
      variant alleles were done. RESULT: Patient country, CYP2B6*6 and ABCB1 c.4036A>G
      (rs3842A>G) genotype were significant predictors of plasma and intracellular
      efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were
      significantly associated with higher plasma efavirenz concentration and their
      allele frequencies were significantly higher in Tanzanians than Ethiopians.
      Tanzanians displayed significantly higher efavirenz plasma concentration at week
      4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma
      concentrations remained significantly higher in Tanzanians even after controlling
      for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses
      indicated a significant decrease in the mean plasma efavirenz concentration by
      week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant
      differences in plasma concentration over time was observed in Ethiopians (p =
      0.84). Intracellular efavirenz concentration and patient country were significant
      predictors of CD4 gain during HAART. CONCLUSION: We report substantial
      differences in efavirenz pharmacokinetics, extent of auto-induction and
      immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not
      solely, due to pharmacogenetic variations. The observed inter-ethnic variations
      in efavirenz plasma exposure may possibly result in varying clinical treatment
      outcome or adverse event profiles between populations.

PMID- 23861839
TI  - Mitochondrial common deletion, a potential biomarker for cancer occurrence, is
      selected against in cancer background: a meta-analysis of 38 studies.
AB  - Mitochondrial dysfunction has been long proposed to play a major role in
      tumorigenesis. Mitochondrial DNA (mtDNA) mutations, especially the mtDNA 4,977 bp
      deletion has been found in patients of various types of cancer. In order to
      comprehend the mtDNA 4,977 bp deletion status in various cancer types, we
      performed a meta-analysis composed of 33 publications, in which a total of 1613
      cancer cases, 1516 adjacent normals and 638 healthy controls were included. When
      all studies were pooled, we found that cancerous tissue carried a lower mtDNA
      4,977 bp deletion frequency than adjacent non-cancerous tissue (OR = 0.43, 95% CI
      = 0.20-0.92, P = 0.03 for heterogeneity test, I(2) = 91.5%) among various types
      of cancer. In the stratified analysis by cancer type the deletion frequency was
      even lower in tumor tissue than in adjacent normal tissue of breast cancer (OR =
      0.19, 95% CI = 0.06-0.61, P = 0.005 for heterogeneity test, I(2)= 82.7%).
      Interestingly, this observation became more significant in the stratified studies
      with larger sample sizes (OR = 0.70, 95% CI = 0.58-0.86, P = 0.0005 for
      heterogeneity test, I(2) = 95.1%). Furthermore, when compared with the normal
      tissue from the matched healthy controls, increased deletion frequencies were
      observed in both adjacent non-cancerous tissue (OR = 3.02, 95% CI = 2.13-4.28,
      P<0.00001 for heterogeneity test, I(2)= 53.7%), and cancerous tissue (OR = 1.36,
      95% CI = 1.04-1.77, P = 0.02 for heterogeneity test, I(2)= 83.5%). This meta
      analysis suggests that the mtDNA 4,977 bp deletion is often found in cancerous
      tissue and thus has the potential to be a biomarker for cancer occurrence in the
      tissue, but at the same time being selected against in various types of carcinoma
      tissues. Larger and better-designed studies are still warranted to confirm these
      findings.

PMID- 23861840
TI  - The serine protease domain of MASP-3: enzymatic properties and crystal structure
      in complex with ecotin.
AB  - Mannan-binding lectin (MBL), ficolins and collectin-11 are known to associate
      with three homologous modular proteases, the MBL-Associated Serine Proteases
      (MASPs). The crystal structures of the catalytic domains of MASP-1 and MASP-2
      have been solved, but the structure of the corresponding domain of MASP-3 remains
      unknown. A link between mutations in the MASP1/3 gene and the rare autosomal
      recessive 3MC (Mingarelli, Malpuech, Michels and Carnevale,) syndrome,
      characterized by various developmental disorders, was discovered recently,
      revealing an unexpected important role of MASP-3 in early developmental
      processes. To gain a first insight into the enzymatic and structural properties
      of MASP-3, a recombinant form of its serine protease (SP) domain was produced and
      characterized. The amidolytic activity of this domain on fluorescent peptidyl
      aminomethylcoumarin substrates was shown to be considerably lower than that of
      other members of the C1r/C1s/MASP family. The E. coli protease inhibitor ecotin
      bound to the SP domains of MASP-3 and MASP-2, whereas no significant interaction
      was detected with MASP-1, C1r and C1s. A tetrameric complex comprising an ecotin
      dimer and two MASP-3 SP domains was isolated and its crystal structure was solved
      and refined to 3.2 A. Analysis of the ecotin/MASP-3 interfaces allows a better
      understanding of the differential reactivity of the C1r/C1s/MASP protease family
      members towards ecotin, and comparison of the MASP-3 SP domain structure with
      those of other trypsin-like proteases yields novel hypotheses accounting for its
      zymogen-like properties in vitro. 

PMID- 23861841
TI  - Transcriptome analysis in sheepgrass (Leymus chinensis): a dominant perennial
      grass of the Eurasian Steppe.
AB  - BACKGROUND: Sheepgrass [Leymus chinensis (Trin.) Tzvel.] is an important
      perennial forage grass across the Eurasian Steppe and is known for its
      adaptability to various environmental conditions. However, insufficient data
      resources in public databases for sheepgrass limited our understanding of the
      mechanism of environmental adaptations, gene discovery and molecular marker
      development. RESULTS: The transcriptome of sheepgrass was sequenced using Roche
      454 pyrosequencing technology. We assembled 952,328 high-quality reads into
      87,214 unigenes, including 32,416 contigs and 54,798 singletons. There were
      15,450 contigs over 500 bp in length. BLAST searches of our database against
      Swiss-Prot and NCBI non-redundant protein sequences (nr) databases resulted in
      the annotation of 54,584 (62.6%) of the unigenes. Gene Ontology (GO) analysis
      assigned 89,129 GO term annotations for 17,463 unigenes. We identified 11,675
      core Poaceae-specific and 12,811 putative sheepgrass-specific unigenes by BLAST
      searches against all plant genome and transcriptome databases. A total of 2,979
      specific freezing-responsive unigenes were found from this RNAseq dataset. We
      identified 3,818 EST-SSRs in 3,597 unigenes, and some SSRs contained unigenes
      that were also candidates for freezing-response genes. Characterizations of
      nucleotide repeats and dominant motifs of SSRs in sheepgrass were also performed.
      Similarity and phylogenetic analysis indicated that sheepgrass is closely related
      to barley and wheat. CONCLUSIONS: This research has greatly enriched sheepgrass
      transcriptome resources. The identified stress-related genes will help us to
      decipher the genetic basis of the environmental and ecological adaptations of
      this species and will be used to improve wheat and barley crops through
      hybridization or genetic transformation. The EST-SSRs reported here will be a
      valuable resource for future gene-phenotype studies and for the molecular
      breeding of sheepgrass and other Poaceae species.

PMID- 23861842
TI  - Measuring myeloperoxidase activity in biological samples.
AB  - BACKGROUND: Enzymatic activity measurements of the highly oxidative enzyme
      myeloperoxidase (MPO), which is implicated in many diseases, are widely used in
      the literature, but often suffer from nonspecificity and lack of uniformity.
      Thus, validation and standardization are needed to establish a robust method that
      is highly specific, sensitive, and reproducible for assaying MPO activity in
      biological samples. PRINCIPAL FINDINGS: We found conflicting results between in
      vivo molecular MR imaging of MPO, which measures extracellular activity, and
      commonly used in vitro MPO activity assays. Thus, we established and validated a
      protocol to obtain extra- and intracellular MPO from murine organs. To validate
      the MPO activity assays, three different classes of MPO activity assays were used
      in spike and recovery experiments. However, these assay methods yielded
      inconsistent results, likely because of interfering substances and other
      peroxidases present in tissue extracts. To circumvent this, we first captured MPO
      with an antibody. The MPO activity of the resultant samples was assessed by ADHP
      and validated against samples from MPO-knockout mice in murine disease models of
      multiple sclerosis, steatohepatitis, and myocardial infarction. We found the
      measurements performed using this protocol to be highly specific and
      reproducible, and when performed using ADHP, to be highly sensitive over a broad
      range. In addition, we found that intracellular MPO activity correlated well with
      tissue neutrophil content, and can be used as a marker to assess neutrophil
      infiltration in the tissue. CONCLUSION: We validated a highly specific and
      sensitive assay protocol that should be used as the standard method for all MPO
      activity assays in biological samples. We also established a method to obtain
      extra- and intracellular MPO from murine organs. Extracellular MPO activity gives
      an estimate of the oxidative stress in inflammatory diseases, while intracellular
      MPO activity correlates well with tissue neutrophil content. A detailed step-by
      step protocol is provided.

PMID- 23861843
TI  - Loneliness: its correlates and association with health behaviours and outcomes in
      nine countries of the former Soviet Union.
AB  - BACKGROUND: Research suggests that the prevalence of loneliness varies between
      countries and that feeling lonely may be associated with poorer health behaviours
      and outcomes. The aim of the current study was to examine the factors associated
      with loneliness, and the relationship between feeling lonely and health
      behaviours and outcomes in the countries of the former Soviet Union (FSU)--a
      region where loneliness has been little studied to date. METHODS: Using data from
      18,000 respondents collected during a cross-sectional survey undertaken in nine
      FSU countries--Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan,
      Moldova, Russia and Ukraine--in 2010/11, country-wise logistic regression
      analysis was conducted to determine: the factors associated with feeling lonely;
      the association between feeling lonely and alcohol consumption, hazardous
      drinking and smoking; and whether feeling lonely was linked to poorer health
      (i.e. poor self-rated health and psychological distress). RESULTS: The prevalence
      of loneliness varied widely among the countries. Being divorced/widowed and low
      social support were associated with loneliness in all of the countries, while
      other factors (e.g. living alone, low locus of control) were linked to loneliness
      in some of the countries. Feeling lonely was connected with hazardous drinking in
      Armenia, Kyrgyzstan and Russia but with smoking only in Kyrgyzstan. Loneliness
      was associated with psychological distress in all of the countries and poor self
      rated health in every country except Kazakhstan and Moldova. CONCLUSIONS:
      Loneliness is associated with worse health behaviours and poorer health in the
      countries of the FSU. More individual country-level research is now needed to
      formulate effective interventions to mitigate the negative effects of loneliness
      on population well-being in the FSU.

PMID- 23861844
TI  - Cysteine methylation controls radical generation in the Cfr radical AdoMet rRNA
      methyltransferase.
AB  - The 'radical S-adenosyl-L-methionine (AdoMet)' enzyme Cfr methylates adenosine
      2503 of the 23S rRNA in the peptidyltransferase centre (P-site) of the bacterial
      ribosome. This modification protects host bacteria, notably methicillin-resistant
      Staphylococcus aureus (MRSA), from numerous antibiotics, including agents (e.g.
      linezolid, retapamulin) that were developed to treat such organisms. Cfr contains
      a single [4Fe-4S] cluster that binds two separate molecules of AdoMet during the
      reaction cycle. These are used sequentially to first methylate a cysteine
      residue, Cys338; and subsequently generate an oxidative radical intermediate that
      facilitates methyl transfer to the unreactive C8 (and/or C2) carbon centres of
      adenosine 2503. How the Cfr active site, with its single [4Fe-4S] cluster,
      catalyses these two distinct activities that each utilise AdoMet as a substrate
      remains to be established. Here, we use absorbance and electron paramagnetic
      resonance (EPR) spectroscopy to investigate the interactions of AdoMet with the
      [4Fe-4S] clusters of wild-type Cfr and a Cys338 Ala mutant, which is unable to
      accept a methyl group. Cfr binds AdoMet with high (~ 10 uM) affinity
      notwithstanding the absence of the RNA cosubstrate. In wild-type Cfr, where
      Cys338 is methylated, AdoMet binding leads to rapid oxidation of the [4Fe-4S]
      cluster and production of 5'-deoxyadenosine (DOA). In contrast, while Cys338 Ala
      Cfr binds AdoMet with equivalent affinity, oxidation of the [4Fe-4S] cluster is
      not observed. Our results indicate that the presence of a methyl group on Cfr
      Cys338 is a key determinant of the activity of the enzyme towards AdoMet, thus
      enabling a single active site to support two distinct modes of AdoMet cleavage. 

PMID- 23861845
TI  - Recent HbA1c values and mortality risk in type 2 diabetes. population-based case
      control study.
AB  - This study aimed to evaluate mortality within 365 days of HbA1c values of <6.5%
      or >9.0% in participants with clinical type 2 diabetes mellitus. A matched nested
      case-control study was implemented, within a cohort of participants with type 2
      diabetes from 2000 to 2008. Conditional logistic regression was used to model the
      odds ratio for mortality adjusting for comorbidity and drug utilisation. There
      were 97,450 participants with type 2 diabetes; 16,585 cases that died during
      follow up were matched to 16,585 controls. The most recent HbA1c value was <6.5%
      (48 mmol/mol) for 22.2% of cases and 24.2% of controls, the HbA1c was >9.0% for
      9.0% of cases and 7.7% of controls. In a complete case analysis, the adjusted
      odds ratio (AOR) for mortality associated with most recent HbA1c <6.5% was 1.31
      (95% confidence interval (CI): 1.21,1.42). After multiple imputation of missing
      HbA1c values the AOR was 1.20 (CI: 1.12,1.28). The complete case analysis gave an
      AOR for HbA1c >9.0% of 1.51 (CI: 1.33, 1.70), in the multiple imputation analysis
      this was 1.29 (1.17,1.41). The risk associated with HbA1c <6.5% was age
      dependent. In the multiple imputation analysis the AOR was 1.53 (CI: 0.84 to
      2.79) at age<55 years but 1.04 (CI: 0.92, 1.17) at age 85 years and over. In non
      randomised data, values of HbA1c that are either <6.5% or >9.0% may be associated
      with increased mortality within one year in clinical type 2 diabetes. Relative
      risks may be higher at younger ages. 

PMID- 23861846
TI  - Conformational dynamics of a ligand-free adenylate kinase.
AB  - Adenylate kinase (AdK) is a phosphoryl-transfer enzyme with important
      physiological functions. Based on a ligand-free open structure and a ligand-bound
      closed structure solved by crystallography, here we use molecular dynamics
      simulations to examine the stability and dynamics of AdK conformations in the
      absence of ligands. We first perform multiple simulations starting from the open
      or the closed structure, and observe their free evolutions during a simulation
      time of 100 or 200 nanoseconds. In all seven simulations starting from the open
      structure, AdK remained stable near the initial conformation. The eight
      simulations initiated from the closed structure, in contrast, exhibited large
      variation in the subsequent evolutions, with most (seven) undergoing large-scale
      spontaneous conformational changes and approaching or reaching the open state. To
      characterize the thermodynamics of the transition, we propose and apply a new
      sampling method that employs a series of restrained simulations to calculate a
      one-dimensional free energy along a curved pathway in the high-dimensional
      conformational space. Our calculated free energy profile features a single
      minimum at the open conformation, and indicates that the closed state, with a
      high (~13 kcal/mol) free energy, is not metastable, consistent with the observed
      behaviors of the unrestrained simulations. Collectively, our simulations suggest
      that it is energetically unfavorable for the ligand-free AdK to access the closed
      conformation, and imply that ligand binding may precede the closure of the
      enzyme. 

PMID- 23861847
TI  - ANOSPEX: a stochastic, spatially explicit model for studying Anopheles
      metapopulation dynamics.
AB  - Anopheles mosquitoes transmit malaria, a major public health problem among many
      African countries. One of the most effective methods to control malaria is by
      controlling the Anopheles mosquito vectors that transmit the parasites.
      Mathematical models have both predictive and explorative utility to investigate
      the pros and cons of different malaria control strategies. We have developed a
      C++ based, stochastic spatially explicit model (ANOSPEX; Ano pheles Spatially
      Explicit) to simulate Anopheles metapopulation dynamics. The model is
      biologically rich, parameterized by field data, and driven by field-collected
      weather data from Macha, Zambia. To preliminarily validate ANOSPEX, simulation
      results were compared to field mosquito collection data from Macha; simulated and
      observed dynamics were similar. The ANOSPEX model will be useful in a predictive
      and exploratory manner to develop, evaluate and implement traditional and novel
      strategies to control malaria, and for understanding the environmental forces
      driving Anopheles population dynamics. 

PMID- 23861848
TI  - The impact of alpha-syntrophin deletion on the changes in tissue structure and
      extracellular diffusion associated with cell swelling under physiological and
      pathological conditions.
AB  - Aquaporin-4 (AQP4) is the primary cellular water channel in the brain and is
      abundantly expressed by astrocytes along the blood-brain barrier and brain
      cerebrospinal fluid interfaces. Water transport via AQP4 contributes to the
      activity-dependent volume changes of the extracellular space (ECS), which affect
      extracellular solute concentrations and neuronal excitability. AQP4 is anchored
      by alpha-syntrophin (alpha-syn), the deletion of which leads to reduced AQP4
      levels in perivascular and subpial membranes. We used the real-time iontophoretic
      method and/or diffusion-weighted magnetic resonance imaging to clarify the impact
      of alpha-syn deletion on astrocyte morphology and changes in extracellular
      diffusion associated with cell swelling in vitro and in vivo. In mice lacking
      alpha-syn, we found higher resting values of the apparent diffusion coefficient
      of water (ADCW) and the extracellular volume fraction (alpha). No significant
      differences in tortuosity (lambda) or non-specific uptake (k'), were found
      between alpha-syn-negative (alpha-syn -/-) and alpha-syn-positive (alpha-syn +/+)
      mice. The deletion of alpha-syn resulted in a significantly smaller relative
      decrease in alpha observed during elevated K(+) (10 mM) and severe hypotonic
      stress (-100 mOsmol/l), but not during mild hypotonic stress (-50 mOsmol/l).
      After the induction of terminal ischemia/anoxia, the final values of ADCW as well
      as of the ECS volume fraction alpha indicate milder cell swelling in alpha-syn -/
      in comparison with alpha-syn +/+ mice. Shortly after terminal ischemia/anoxia
      induction, the onset of a steep rise in the extracellular potassium concentration
      and an increase in lambda was faster in alpha-syn -/- mice, but the final values
      did not differ between alpha-syn -/- and alpha-syn +/+ mice. This study reveals
      that water transport through AQP4 channels enhances and accelerates astrocyte
      swelling. The substantially altered ECS diffusion parameters will likely affect
      the movement of neuroactive substances and/or trophic factors, which in turn may
      modulate the extent of tissue damage and/or drug distribution. 

PMID- 23861849
TI  - Neurogenic detrusor overactivity is associated with decreased expression and
      function of the large conductance voltage- and Ca(2+)-activated K(+) channels.
AB  - Patients suffering from a variety of neurological diseases such as spinal cord
      injury, Parkinson's disease, and multiple sclerosis often develop neurogenic
      detrusor overactivity (NDO), which currently lacks a universally effective
      therapy. Here, we tested the hypothesis that NDO is associated with changes in
      detrusor smooth muscle (DSM) large conductance Ca(2+)-activated K(+) (BK) channel
      expression and function. DSM tissue samples from 33 patients were obtained during
      open bladder surgeries. NDO patients were clinically characterized preoperatively
      with pressure-flow urodynamics demonstrating detrusor overactivity, in the
      setting of a clinically relevant neurological condition. Control patients did not
      have overactive bladder and did not have a clinically relevant neurological
      disease. We conducted quantitative polymerase chain reactions (qPCR), perforated
      patch-clamp electrophysiology on freshly-isolated DSM cells, and functional
      studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO
      patients showed decreased BK channel mRNA expression in comparison to controls.
      Patch-clamp experiments demonstrated reduced whole cell and transient BK currents
      (TBKCs) in freshly-isolated DSM cells from NDO patients. Functional studies on
      DSM contractility showed that spontaneous phasic contractions had a decreased
      sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips
      isolated from NDO patients. These results reveal the novel finding that NDO is
      associated with decreased DSM BK channel expression and function leading to
      increased DSM excitability and contractility. BK channel openers or BK channel
      gene transfer could be an alternative strategy to control NDO. Future clinical
      trials are needed to evaluate the value of BK channel opening drugs or gene
      therapies for NDO treatment and to identify any possible adverse effects. 

PMID- 23861850
TI  - Nonlinear distribution pattern of hibernating bats in caves along an elevational
      gradient in mountain (Carpathians, Southern Poland).
AB  - BACKGROUND: Thermal gradients along changes in elevation in mountainous
      environments are reflected by different biotas. Although there have been studies
      of elevation variation in bat assemblages in summer, winter changes in the same
      gradients remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this
      study was to document changes in the species composition of bats hibernating in
      caves along a temperate elevational gradient. We studied 70 caves between from
      300 m to 1,930 m altitude along a slope of the Carpathian Mountains in southern
      Poland. We recorded changes in bats, including species richness, abundance,
      altitudinal distribution and dominance during consecutive winters between 2003
      and 2009. Similarity of dominance of faunal structure was assessed by using the
      Bray-Curtis similarity index. We used the generalised additive model and
      rarefaction to study the variation in species richness, and generalized additive
      mixed models to examine the effect of abiotic factors on the qualitative and
      quantitative structure of bat assemblages. During 351 surveys we recorded 13,856
      hibernating bats from 15 species. Species richness peaked around mid-elevation
      (1,100-1,400 m a.s.l.) with richness declining at both higher and lower
      elevations. Based on the results of a cluster analysis, we could distinguish
      among four altitudinal zones that differed in species richness and dominance
      structure. CONCLUSIONS/SIGNIFICANCE: This is the first study documenting changes
      in species richness and variation of structure of bats hibernating in caves along
      an elevational gradient. The most surprising and key finding is the fact that
      changes in the structure of assemblages of hibernating bats along the altitudinal
      gradient occurred in jumps, forming zones similar to those observed in the
      vegetation zones. Moreover, species richness and dominance structure of
      assemblages of hibernating bats in the mountains depended not only on location
      above sea level, but also on local geomorphologic conditions which strongly
      affected the microclimate of the caves.

PMID- 23861851
TI  - Sex differences in colorectal cancer survival: population-based analysis of
      164,996 colorectal cancer patients in Germany.
AB  - Risk of colorectal cancer (CRC) is considerably higher in men compared to women;
      however, there is inconclusive evidence of sex differences in CRC prognosis. We
      aimed to assess and explain sex differences in 5-year relative survival using
      standard and model-based period analysis among 164,996 patients diagnosed with
      CRC from 1997 to 2006 and reported to 11 German cancer registries covering a
      population of 33 million inhabitants. Age-adjusted 5-year relative survival was
      higher in women (64.5% vs. 61.9%, P<0.0001). A substantial survival advantage of
      women was confirmed in multivariate analysis after adjusting for CRC stage and
      subsite in subjects under 65 years of age (relative excess risk, RER 0.86, 95% CI
      0.82-0.90), but not in older subjects (RER 1.01, 95% CI 0.98-1.04); this pattern
      was similar in the 1st and in the 2nd to 5th year after diagnosis. The survival
      advantage of women varied by CRC stage and age and was most pronounced for
      localized disease (RERs 0.59-0.88 in various age subgroups) and in patients under
      45 years of age (RERs 0.59, 0.72 and 0.76 in patients with localized, regional or
      advanced disease, respectively). On the contrary, sex differences in survival did
      not vary by location of CRC. In conclusion, our large population-based study
      confirmed a survival advantage of female compared to male CRC patients, most
      notably in young and middle aged patients and patients with localized disease.
      The effect of sex hormones, either endogenous or through hormonal replacement
      therapy, might be the most plausible explanation for the observed patterns. 

PMID- 23861852
TI  - Epo receptors are not detectable in primary human tumor tissue samples.
AB  - Erythropoietin (Epo) is a cytokine that binds and activates an Epo receptor
      (EpoR) expressed on the surface of erythroid progenitor cells to promote
      erythropoiesis. While early studies suggested EpoR transcripts were expressed
      exclusively in the erythroid compartment, low-level EpoR transcripts were
      detected in nonhematopoietic tissues and tumor cell lines using sensitive RT-PCR
      methods. However due to the widespread use of nonspecific anti-EpoR antibodies
      there are conflicting data on EpoR protein expression. In tumor cell lines and
      normal human tissues examined with a specific and sensitive monoclonal antibody
      to human EpoR (A82), little/no EpoR protein was detected and it was not
      functional. In contrast, EpoR protein was reportedly detectable in a breast tumor
      cell line (MCF-7) and breast cancer tissues with an anti-EpoR polyclonal antibody
      (M-20), and functional responses to rHuEpo were reported with MCF-7 cells. In
      another study, a functional response was reported with the lung tumor cell line
      (NCI-H838) at physiological levels of rHuEpo. However, the specificity of M-20 is
      in question and the absence of appropriate negative controls raise questions
      about possible false-positive effects. Here we show that with A82, no EpoR
      protein was detectable in normal human and matching cancer tissues from breast,
      lung, colon, ovary and skin with little/no EpoR in MCF-7 and most other breast
      and lung tumor cell lines. We show further that M-20 provides false positive
      staining with tissues and it binds to a non-EpoR protein that migrates at the
      same size as EpoR with MCF-7 lysates. EpoR protein was detectable with NCI-H838
      cells, but no rHuEpo-induced phosphorylation of AKT, STAT3, pS6RP or STAT5 was
      observed suggesting the EpoR was not functional. Taken together these results
      raise questions about the hypothesis that most tumors express high levels of
      functional EpoR protein. 

PMID- 23861853
TI  - The effects of different wavelength UV photofunctionalization on micro-arc
      oxidized titanium.
AB  - Many challenges exist in improving early osseointegration, one of the most
      critical factors in the long-term clinical success of dental implants. Recently,
      ultraviolet (UV) light-mediated photofunctionalization of titanium as a new
      potential surface treatment has aroused great interest. This study examines the
      bioactivity of titanium surfaces treated with UV light of different wavelengths
      and the underlying associated mechanism. Micro-arc oxidation (MAO) titanium
      samples were pretreated with UVA light (peak wavelength of 360 nm) or UVC light
      (peak wavelength of 250 nm) for up to 24 h. UVC treatment promoted the
      attachment, spread, proliferation and differentiation of MG-63 osteoblast-like
      cells on the titanium surface, as well as the capacity for apatite formation in
      simulated body fluid (SBF). These biological influences were not observed after
      UVA treatment, apart from a weaker effect on apatite formation. The enhanced
      bioactivity was substantially correlated with the amount of Ti-OH groups, which
      play an important role in improving the hydrophilicity, along with the removal of
      hydrocarbons on the titanium surface. Our results showed that both UVA and UVC
      irradiation altered the chemical properties of the titanium surface without
      sacrificing its excellent physical characteristics, suggesting that this
      technology has extensive potential applications and merits further investigation.

PMID- 23861854
TI  - Reducing the intensity and volume of interval training diminishes cardiovascular
      adaptation but not mitochondrial biogenesis in overweight/obese men.
AB  - OBJECTIVE: The purpose of this research was to determine if the adaptations to
      high intensity interval training (HIT) are mitigated when both intensity and
      training volume (i.e. exercise energy expenditure) are reduced. METHODS: 19
      overweight/obese, sedentary males (Age: 22.7+/-3.9 yrs, Body Mass Index: 31.4+/
      2.6 kg/m(2), Waist Circumference: 106.5+/-6.6 cm) performed 9 sessions of
      interval training using a 1-min on, 1-min off protocol on a cycle ergometer over
      three weeks at either 70% (LO) or 100% (HI) peak work rate. RESULTS: Cytochrome
      oxidase I protein content, cytochrome oxidase IV protein content, and citrate
      synthase maximal activity all demonstrated similar increases between groups with
      a significant effect of training for each. beta-hydroxyacyl-CoA dehydrogenase
      maximal activity tended to increase with training but did not reach statistical
      significance (p = 0.07). Peroxisome proliferator-activated receptor gamma
      coactivator-1alpha and silent mating type information regulator 2 homolog 1
      protein contents also increased significantly (p = 0.047), while AMP-activated
      protein kinase protein content decreased following the intervention (p = 0.019).
      VO2peak increased by 11.0+/-7.4% and 27.7+/-4.4% in the LO and HI groups
      respectively with significant effects of both training (p<0.001) and interaction
      (p = 0.027). Exercise performance improved by 8.6+/-7.6% in the LO group and
      14.1+/-4.3% in the HI group with a significant effect of training and a
      significant difference in the improvement between groups. There were no
      differences in perceived enjoyment or self-efficacy between groups despite
      significantly lower affect scores during training in the HI group. CONCLUSIONS:
      While improvements in aerobic capacity and exercise performance were different
      between groups, changes in oxidative capacity were similar despite reductions in
      both training intensity and volume.

PMID- 23861855
TI  - Dual mechanisms of translation initiation of the full-length HIV-1 mRNA
      contribute to gag synthesis.
AB  - The precursor group-specific antigen (pr55(Gag)) is central to HIV-1 assembly.
      Its expression alone is sufficient to assemble into virus-like particles. It also
      selects the genomic RNA for encapsidation and is involved in several important
      virus-host interactions for viral assembly and restriction, making its synthesis
      essential for aspects of viral replication. Here, we show that the initiation of
      translation of the HIV-1 genomic RNA is mediated through both a cap-dependent and
      an internal ribosome entry site (IRES)-mediated mechanisms. In support of this
      notion, pr55(Gag) synthesis was maintained at 70% when cap-dependent translation
      initiation was blocked by the expression of eIF4G- and PABP targeting viral
      proteases in two in vitro systems and in HIV-1-expressing cells directly infected
      with poliovirus. While our data reveal that IRES-dependent translation of the
      viral genomic RNA ensures pr55(Gag) expression, the synthesis of other HIV-1
      proteins, including that of pr160(Gag/Pol), Vpr and Tat is suppressed early
      during progressive poliovirus infection. The data presented herein implies that
      the unspliced HIV-1 genomic RNA utilizes both cap-dependent and IRES-dependent
      translation initiation to supply pr55(Gag) for virus assembly and production. 

PMID- 23861856
TI  - Y-chromosome DNA is present in the blood of female dogs suggesting the presence
      of fetal microchimerism.
AB  - Fetal microchimerism has been suggested to play contradictory roles in women's
      health, with factors including age of the recipient, time elapsed since
      microchimerism occurred, and microchimeric cell type modulating disease. Both
      beneficial and harmful effects have been identified in wound healing and tissue
      regeneration, immune mediated disease, and cancer. This area of research is
      relatively new, and hindered by the time course from occurrence of fetal
      microchimerism to the multi-factorial development of disease. Dogs represent an
      excellent model for study of fetal microchimerism, as they share our environment,
      have a naturally condensed lifespan, and spontaneously develop immune-mediated
      diseases and cancers similar to their human counterparts. However, fetal
      microchimerism has not been described in dogs. These experiments sought
      preliminary evidence that dogs develop fetal microchimerism following pregnancy.
      We hypothesized that Y chromosomal DNA would be detected in the peripheral blood
      mononuclear cells of female dogs collected within two months of parturition. We
      further hypothesized that Y chromosomal DNA would be detected in banked whole
      blood DNA samples from parous female Golden Retrievers with at least one male
      puppy in a prior litter. Amplification of DNA extracted from five female Golden
      Retrievers that had whelped within the two months prior to collection revealed
      strong positive bands for the Y chromosome. Of banked, parous samples, 36%
      yielded positive bands for the Y chromosome. This is the first report of
      persistent Y chromosomal DNA in post-partum female dogs and these results suggest
      that fetal microchimerism occurs in the canine species. Evaluation of the
      contributions of fetal microchimeric cells to disease processes in dogs as a
      model for human disease is warranted. 

PMID- 23861857
TI  - Novel PI3Kgamma mutation in a 44-year-old man with chronic infections and chronic
      pelvic pain.
AB  - A 44-year-old man is presented here with 14 years of chronic purulent sinusitis,
      a chronic fungal rash of the scrotum, and chronic pelvic pain. Treatment with
      antifungal therapy resulted in symptom improvement, however he was unable to
      establish an effective long-term treatment regimen, resulting in debilitating
      symptoms. He had undergone extensive work-up without identifying a clear
      underlying etiology, although Candida species were cultured from the prostatic
      fluid. 100 genes involved in the cellular immune response were sequenced and a
      missense mutation was identified in the Ras-binding domain of PI3Kgamma.
      PI3Kgamma is a crucial signaling element in leukotaxis and other leukocyte
      functions. We hypothesize that his mutation led to his chronic infections and
      pelvic pain. 

PMID- 23861858
TI  - Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and
      is a future component of donor scoring criteria.
AB  - CDKN2A is a proven and validated biomarker of ageing which acts as an off switch
      for cell proliferation. We have demonstrated previously that CDKN2A is the most
      robust and the strongest pre-transplant predictor of post-transplant serum
      creatinine when compared to "Gold Standard" clinical factors, such as cold
      ischaemic time and donor chronological age. This report shows that CDKN2A is
      better than telomere length, the most celebrated biomarker of ageing, as a
      predictor of post-transplant renal function. It also shows that CDKN2A is as
      strong a determinant of post-transplant organ function when compared to extended
      criteria (ECD) kidneys. A multivariate analysis model was able to predict up to
      27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was
      also able to strongly predict delayed graft function. A pre-transplant donor risk
      classification system based on CDKN2A and ECD criteria is shown to be feasible
      and commendable for implementation in the near future.

PMID- 23861859
TI  - Inhibition of the water oxidizing complex of photosystem II and the reoxidation
      of the quinone acceptor QA- by Pb2+.
AB  - The action of the environmental toxic Pb(2+) on photosynthetic electron transport
      was studied in thylakoid membranes isolated from spinach leaves. Fluorescence and
      thermoluminescence techniques were performed in order to determine the mode of
      Pb(2+) action in photosystem II (PSII). The invariance of fluorescence
      characteristics of chlorophyll a (Chl a) and magnesium tetraphenylporphyrin
      (MgTPP), a molecule structurally analogous to Chl a, in the presence of Pb(2+)
      confirms that Pb cation does not interact directly with chlorophyll molecules in
      PSII. The results show that Pb interacts with the water oxidation complex thus
      perturbing charge recombination between the quinone acceptors of PSII and the S2
      state of the Mn4Ca cluster. Electron transfer between the quinone acceptors QA
      and QB is also greatly retarded in the presence of Pb(2+). This is proposed to be
      owing to a transmembrane modification of the acceptor side of the photosystem. 

PMID- 23861860
TI  - Nosocomial bloodstream infections in Brazilian pediatric patients: microbiology,
      epidemiology, and clinical features.
AB  - BACKGROUND: Nosocomial bloodstream infections (nBSIs) are an important cause of
      morbidity and mortality and are the most frequent type of nosocomial infection in
      pediatric patients. METHODS: We identified the predominant pathogens and
      antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric
      patients (<=16 years of age) in the Brazilian Prospective Surveillance for nBSIs
      at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project). RESULTS:
      In our study a total of 2,563 cases of nBSI were reported by hospitals
      participating in the Br SCOPE project. Among these, 342 clinically significant
      episodes of BSI were identified in pediatric patients (<=16 years of age). Ninety
      six percent of BSIs were monomicrobial. Gram-negative organisms caused 49.0% of
      these BSIs, Gram-positive organisms caused 42.6%, and fungi caused 8.4%. The most
      common pathogens were Coagulase-negative staphylococci (CoNS) (21.3%), Klebsiella
      spp. (15.7%), Staphylococcus aureus (10.6%), and Acinetobacter spp. (9.2%). The
      crude mortality was 21.6% (74 of 342). Forty-five percent of nBSIs occurred in a
      pediatric or neonatal intensive-care unit (ICU). The most frequent underlying
      conditions were malignancy, in 95 patients (27.8%). Among the potential factors
      predisposing patients to BSI, central venous catheters were the most frequent
      (66.4%). Methicillin resistance was detected in 37 S. aureus isolates (27.1%). Of
      the Klebsiella spp. isolates, 43.2% were resistant to ceftriaxone. Of the
      Acinetobacter spp. and Pseudomonas aeruginosa isolates, 42.9% and 21.4%,
      respectively, were resistant to imipenem. CONCLUSIONS: In our multicenter study,
      we found a high mortality and a large proportion of gram-negative bacilli with
      elevated levels of resistance in pediatric patients.

PMID- 23861861
TI  - Follicular helper T Cells (Tfh) and IL-21 involvement in the pathogenesis of
      bullous pemphigoid.
AB  - The pathogenesis of bullous pemphigoid (BP) is characterized by the T cell
      dependent production of autoantibodies. Recent studies have indicated that
      follicular T helper cells (Tfh), the key modulator of B cell activation and
      autoantibody production, are critical in the development of several autoimmune
      diseases. Tfh cells perform their functions via IL-21, their hallmark cytokine.
      In the present study, the frequencies of Tfh cells were investigated in the
      peripheral blood samples of BP patients to evaluate whether Tfh cells involve in
      this clinical entity. Significantly higher Tfh cell counts were observed in the
      peripheral blood of BP patients than those in healthy controls (median: 11.25%
      vs. 4.95%, respectively; P<0.001). Additionally, the serum IL-21 levels in BP
      patients were higher than those of the healthy controls (median: 103.98 pg/mL vs
      46.77 pg/mL, respectively; P<0.001). The frequencies of Tfh cells and IL-21
      levels were both positively correlated with anti-BP180-NC16A autoantibody titers
      (R = 0.712, P<0.01 and R = 0.578, P = 0.030, respectively). After effective
      therapy, the frequencies of Tfh cells as well as the serum IL-21 levels in BP
      patients decreased along with clinical improvement. Most importantly, Tfh
      depleted CD4(+) T cells and anti-IL-21 neutralization antibody could inhibit the
      T cell-induced B cell activation and secretion of BP autoantibody in vitro. Those
      results suggest that Tfh cells play an important role in autoantibody production
      and are involved in the pathogenesis of BP. 

PMID- 23861862
TI  - Differences in aqueous concentrations of cytokines in macular edema secondary to
      branch and central retinal vein occlusion.
AB  - PURPOSE: This study investigates the differential aqueous concentrations of
      interleukin 6, 8, 1beta (IL-6, IL-8, IL-1beta, respectively), serum amyloid A
      (SAA), transforming growth factor (TGF)-beta, basic fibroblast growth factor
      (bFGF), and vascular endothelial growth factor (VEGF) in eyes with macular edema
      as a result of a branch retinal vein occlusion (BRVO) or central retinal vein
      occlusion (CRVO). PRINCIPAL FINDINGS: Significantly higher concentrations of IL
      6, IL-8, IL-1beta, TGF-beta, bFGF, SAA, and VEGF were found in the aqueous humor
      of CRVO and BRVO patients than in the aqueous humor of control patients. A
      significant correlation was observed between the concentration of bFGF and the
      inner central macular thickness (CMT) of BRVO patients (r = 0.688; P = 0.02). A
      significant correlation was observed between the concentration of SAA and both
      the full and outer CMT of the ischemic group (r = 0.545 and 0.683, respectively;
      P = 0.04 and 0.01, respectively). In the non-ischemic group, the level of IL-6
      was significantly associated with inner CMT (r = 0.560; P = 0.03). The full and
      outer CMT was significantly reduced in CRVO patients when compared with BRVO
      patients (P = 0.02 and 0.02, respectively) after injection of intravitreal
      bevacizumab (IVB) at 4 weeks. SIGNIFICANCE: Serum amyloid A as a major protein
      involved in the acute and chronic stages of inflammation, and IL-6 and bFGF were
      significantly associated with the extent of macular edema in patients with RVO.
      Besides VEGF, other inflammatory cytokines and angiogenesic factors may be
      associated with RVO. This finding may have implications for the medical treatment
      of RVO.

PMID- 23861863
TI  - Non-linear interactions determine the impact of sea-level rise on estuarine
      benthic biodiversity and ecosystem processes.
AB  - Sea-level rise induced by climate change may have significant impacts on the
      ecosystem functions and ecosystem services provided by intertidal sediment
      ecosystems. Accelerated sea-level rise is expected to lead to steeper beach
      slopes, coarser particle sizes and increased wave exposure, with consequent
      impacts on intertidal ecosystems. We examined the relationships between
      abundance, biomass, and community metabolism of benthic fauna with beach slope,
      particle size and exposure, using samples across a range of conditions from three
      different locations in the UK, to determine the significance of sediment particle
      size beach slope and wave exposure in affecting benthic fauna and ecosystem
      function in different ecological contexts. Our results show that abundance,
      biomass and oxygen consumption of intertidal macrofauna and meiofauna are
      affected significantly by interactions among sediment particle size, beach slope
      and wave exposure. For macrofauna on less sloping beaches, the effect of these
      physical constraints is mediated by the local context, although for meiofauna and
      for macrofauna on intermediate and steeper beaches, the effects of physical
      constraints dominate. Steeper beach slopes, coarser particle sizes and increased
      wave exposure generally result in decreases in abundance, biomass and oxygen
      consumption, but these relationships are complex and non-linear. Sea-level rise
      is likely to lead to changes in ecosystem structure with generally negative
      impacts on ecosystem functions and ecosystem services. However, the impacts of
      sea-level rise will also be affected by local ecological context, especially for
      less sloping beaches. 

PMID- 23861864
TI  - Recognising and treatment seeking for acute bacterial meningitis in adults and
      children in resource-poor settings: a qualitative study.
AB  - OBJECTIVE: High mortality burden from Acute Bacterial Meningitis (ABM) in
      resource-poor settings has been frequently blamed on delays in treatment seeking.
      We explored treatment-seeking pathways from household to primary health care and
      referral for ABM in Malawi. DESIGN: A cross-sectional qualitative study using
      narrative in-depth interviews, semi-structured interviews and focus group
      discussions. PARTICIPANTS: Adults and children with proven and probable acute
      bacterial meningitis and/or their carers; adults from urban and peri-urban
      communities; and primary health care workers (HCW). SETTING: Queen Elizabeth
      Central Hospital (QECH), urban and peri-urban private and government primary
      health centres and communities in Blantyre District, Malawi. RESULTS: Whilst
      communities associated meningitis with a stiff neck, in practice responses
      focused on ability to recognise severe illness. Misdiagnosis of meningitis as
      malaria was common. Subsequent action by families depended on the extent to which
      normal social life was disrupted by the illness and depended on the age and
      social position of the sufferer. Seizures and convulsions were considered severe
      symptoms but were often thought to be malaria. Presumptive malaria treatment at
      home often delayed formal treatment seeking. Further delays in treatment seeking
      were caused by economic barriers and perceptions of inefficient or inadequate
      primary health services. CONCLUSIONS: Given the difficulties in diagnosis of
      meningitis where malaria is common, any intervention for ABM at primary level
      must focus on recognising severe illness, and encouraging action at the
      household, community and primary health levels. Overcoming barriers to
      recognition and social constraints at community level require broad community
      based strategies and may provide a route to addressing poor clinical outcomes.

PMID- 23861865
TI  - Shared midgut binding sites for Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac and Cry1Fa
      proteins from Bacillus thuringiensis in two important corn pests, Ostrinia
      nubilalis and Spodoptera frugiperda.
AB  - First generation of insect-protected transgenic corn (Bt-corn) was based on the
      expression of Cry1Ab or Cry1Fa proteins. Currently, the trend is the combination
      of two or more genes expressing proteins that bind to different targets. In
      addition to broadening the spectrum of action, this strategy helps to delay the
      evolution of resistance in exposed insect populations. One of such examples is
      the combination of Cry1A.105 with Cry1Fa and Cry2Ab to control O. nubilalis and
      S. frugiperda. Cry1A.105 is a chimeric protein with domains I and II and the C
      terminal half of the protein from Cry1Ac, and domain III almost identical to
      Cry1Fa. The aim of the present study was to determine whether the chimeric
      Cry1A.105 has shared binding sites either with Cry1A proteins, with Cry1Fa, or
      with both, in O. nubilalis and in S. frugiperda. Brush-border membrane vesicles
      (BBMV) from last instar larval midguts were used in competition binding assays
      with (125)I-labeled Cry1A.105, Cry1Ab, and Cry1Fa, and unlabeled Cry1A.105,
      Cry1Aa, Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab and Cry2Ae. The results showed that
      Cry1A.105, Cry1Ab, Cry1Ac and Cry1Fa competed with high affinity for the same
      binding sites in both insect species. However, Cry2Ab and Cry2Ae did not compete
      for the binding sites of Cry1 proteins. Therefore, according to our results, the
      development of cross-resistance among Cry1Ab/Ac, Cry1A.105, and Cry1Fa proteins
      is possible in these two insect species if the alteration of shared binding sites
      occurs. Conversely, cross-resistance between these proteins and Cry2A proteins is
      very unlikely in such case. 

PMID- 23861866
TI  - Quantification of collagen ultrastructure after penetrating keratoplasty -
      implications for corneal biomechanics.
AB  - PURPOSE: To quantify long-term changes in stromal collagen ultrastructure
      following penetrating keratoplasty (PK), and evaluate their possible implications
      for corneal biomechanics. METHODS: A pair of 16 mm post-mortem corneo-scleral
      buttons was obtained from a patient receiving bilateral penetrating keratoplasty
      12 (left)/28 (right) years previously. Small-angle x-ray scattering quantified
      collagen fibril spacing, diameter and spatial order at 0.5 mm or 0.25 mm
      intervals along linear scans across the graft margin. Corresponding control data
      was collected from two corneo-scleral buttons with no history of refractive
      surgery. Wide-angle x-ray scattering quantified collagen fibril orientation at
      0.25 mm (horizontal)*0.25 mm (vertical) intervals across both PK specimens.
      Quantification of orientation changes in the graft margin were verified by
      equivalent analysis of data from a 13 year post-operative right PK specimen
      obtained from a second patient in a previous study, and comparison made with new
      and published data from normal corneas. RESULTS: Marked changes to normal fibril
      alignment, in favour of tangentially oriented collagen, were observed around the
      entire graft margin in all PK specimens. The total number of meridional fibrils
      in the wound margin was observed to decrease by up to 40%, with the number of
      tangentially oriented fibrils increasing by up to 46%. As a result, in some
      locations the number of fibrils aligned parallel to the wound outnumbered those
      spanning it by up to five times. Localised increases in fibril spacing and
      diameter, with an accompanying reduction in matrix order, were also evident.
      CONCLUSIONS: Abnormal collagen fibril size and spatial order within the PK graft
      margin are indicative of incomplete stromal wound remodelling and the long term
      persistence of fibrotic scar tissue. Lasting changes in collagen fibril
      orientation in and around PK wounds may alter corneal biomechanics and compromise
      the integrity of the graft-host interface in the long term.

PMID- 23861867
TI  - Nonstructural 5A protein of hepatitis C virus interacts with pyruvate carboxylase
      and modulates viral propagation.
AB  - Hepatitis C virus (HCV) is highly dependent on cellular factors for its own
      propagation. By employing tandem affinity purification method, we identified
      pyruvate carboxylase (PC) as a cellular partner for NS5A protein. NS5A interacted
      with PC through the N-terminal region of NS5A and the biotin carboxylase domain
      of PC. PC expression was decreased in cells expressing NS5A and HCV-infected
      cells. Promoter activity of PC was also decreased by NS5A protein. However, FAS
      expression was increased in cells expressing NS5A and cell culture grown HCV
      (HCVcc)-infected cells. Silencing of PC promoted fatty acid synthase (FAS)
      expression level. These data suggest HCV may modulate PC via NS5A protein for its
      own propagation. 

PMID- 23861868
TI  - The effects of threonine phosphorylation on the stability and dynamics of the
      central molecular switch region of 18.5-kDa myelin basic protein.
AB  - The classic isoforms of myelin basic protein (MBP) are essential for the
      formation and maintenance of myelin in the central nervous system of higher
      vertebrates. The protein is involved in all facets of the development,
      compaction, and stabilization of the multilamellar myelin sheath, and also
      interacts with cytoskeletal and signaling proteins. The predominant 18.5-kDa
      isoform of MBP is an intrinsically-disordered protein that is a candidate auto
      antigen in the human demyelinating disease multiple sclerosis. A highly-conserved
      central segment within classic MBP consists of a proline-rich region (murine 18.5
      kDa sequence -T92-P93-R94-T95-P96-P97-P98-S99-) containing a putative SH3-ligand,
      adjacent to a region that forms an amphipathic alpha-helix (P82-I90) upon
      interaction with membranes, or under membrane-mimetic conditions. The T92 and T95
      residues within the proline-rich region can be post-translationally modified
      through phosphorylation by mitogen-activated protein (MAP) kinases. Here, we have
      investigated the structure of the alpha-helical and proline-rich regions in
      dilute aqueous buffer, and have evaluated the effects of phosphorylation at T92
      and T95 on the stability and dynamics of the alpha-helical region, by utilizing
      four 36-residue peptides (S72-S107) with differing phosphorylation status.
      Nuclear magnetic resonance spectroscopy reveals that both the alpha-helical as
      well as the proline-rich regions are disordered in aqueous buffer, whereas they
      are both structured in a lipid environment (cf., Ahmed et al., Biochemistry 51,
      7475-9487, 2012). Thermodynamic analysis of trifluoroethanol-titration curves
      monitored by circular dichroism spectroscopy reveals that phosphorylation,
      especially at residue T92, impedes formation of the amphipathic alpha-helix. This
      conclusion is supported by molecular dynamics simulations, which further
      illustrate that phosphorylation reduces the folding reversibility of the alpha
      helix upon temperature perturbation and affect the global structure of the
      peptides through altered electrostatic interactions. The results support the
      hypothesis that the central conserved segment of MBP constitutes a molecular
      switch in which the conformation and/or intermolecular interactions are mediated
      by phosphorylation/dephosphorylation at T92 and T95. 

PMID- 23861869
TI  - Cytomegalovirus pp71 protein is expressed in human glioblastoma and promotes pro
      angiogenic signaling by activation of stem cell factor.
AB  - Glioblastoma multiforme (GBM) is a highly malignant primary central nervous
      system neoplasm characterized by tumor cell invasion, robust angiogenesis, and a
      mean survival of 15 months. Human cytomegalovirus (HCMV) infection is present in
      >90% of GBMs, although the role the virus plays in GBM pathogenesis is unclear.
      We report here that HCMV pp71, a viral protein previously shown to promote cell
      cycle progression, is present in a majority of human GBMs and is preferentially
      expressed in the CD133+, cancer stem-like cell population. Overexpression of pp71
      in adult neural precursor cells resulted in potent induction of stem cell factor
      (SCF), an important pro-angiogenic factor in GBM. Using double
      immunofluorescence, we demonstrate in situ co-localization of pp71 and SCF in
      clinical GBM specimens. pp71 overexpression in both normal and transformed glial
      cells increased SCF secretion and this effect was specific, since siRNA mediated
      knockdown of pp71 or treatment with the antiviral drug cidofovir resulted in
      decreased expression and secretion of SCF by HCMV-infected cells. pp71- induced
      upregulation of SCF resulted in downstream activation of its putative endothelial
      cell receptor, c-kit, and angiogenesis as measured by increased capillary tube
      formation in vitro. We demonstrate that pp71 induces a pro-inflammatory response
      via activation of NFKappaB signaling which drives SCF expression. Furthermore, we
      show that pp71 levels and NFKB activation are selectively augmented in the
      mesenchymal subtype of human GBMs, characterized by worst patient outcome,
      suggesting that HCMV pp71-induced paracrine signaling may contribute to the
      aggressive phenotype of this human malignancy. 

PMID- 23861870
TI  - Analysis of whitefly transcriptional responses to Beauveria bassiana infection
      reveals new insights into insect-fungus interactions.
AB  - BACKGROUND: The fungal pathogen, Beauveria bassiana, is an efficient biocontrol
      agent against a variety of agricultural pests. A thorough understanding of the
      basic principles of insect-fungus interactions may enable the genetic
      modification of Beauveria bassiana to enhance its virulence. However, the
      molecular mechanism of insect response to Beauveria bassiana infection is poorly
      understood, let alone the identification of fungal virulent factors involved in
      pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Here, next generation sequencing
      technology was applied to examine the expression of whitefly (Bemisia tabaci)
      genes in response to the infection of Beauveria bassiana. Results showed that,
      compared to control, 654 and 1,681genes were differentially expressed at 48 hours
      and 72 hours post-infected whiteflies, respectively. Functional and enrichment
      analyses indicated that the DNA damage stimulus response and drug metabolism were
      important anti-fungi strategies of the whitefly. Mitogen-activated protein kinase
      (MAPK) pathway was also likely involved in the whitefly defense responses.
      Furthermore, the notable suppression of general metabolism and ion transport
      genes observed in 72 hours post-infected B. tabaci might be manipulated by fungal
      secreted effectors. By mapping the sequencing tags to B. bassiana genome, we also
      identified a number of differentially expressed fungal genes between the early
      and late infection stages. These genes are generally associated with fungal cell
      wall synthesis and energy metabolism. The expression of fungal cell wall protein
      genes might play an important role in fungal pathogenesis and the dramatically up
      regulated enzymes of carbon metabolism indicate the increasing usage of energy
      during the fungal infection. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this is
      the first report on the molecular mechanism of fungus-whitefly interactions. Our
      results provide a road map for future investigations on insect-pathogen
      interactions and genetically modifying the fungus to enhance its efficiency in
      whitefly control.

PMID- 23861871
TI  - Cryptic genomic rearrangements in three patients with 46,XY disorders of sex
      development.
AB  - BACKGROUND: 46,XY disorders of sex development (46,XY DSD) are genetically
      heterogeneous conditions. Recently, a few submicroscopic genomic rearrangements
      have been reported as novel genetic causes of 46,XY DSD. METHODOLOGY/PRINCIPAL
      FINDINGS: To clarify the role of cryptic rearrangements in the development of
      46,XY DSD, we performed array-based comparative genomic hybridization analysis
      for 24 genetic males with genital abnormalities. Heterozygous submicroscopic
      deletions were identified in three cases (cases 1-3). A ~8.5 Mb terminal deletion
      at 9p24.1-24.3 was detected in case 1 that presented with complete female-type
      external genitalia and mental retardation; a ~2.0 Mb interstitial deletion at
      20p13 was identified in case 2 with ambiguous external genitalia and short
      stature; and a ~18.0 Mb interstitial deletion at 2q31.1-32 was found in case 3
      with ambiguous external genitalia, mental retardation and multiple anomalies. The
      genital abnormalities of case 1 could be ascribed to gonadal dysgenesis caused by
      haploinsufficiency of DMRT1, while those of case 3 were possibly associated with
      perturbed organogenesis due to a deletion of the HOXD cluster. The deletion in
      case 2 affected 36 genes, none of which have been previously implicated in sex
      development. CONCLUSIONS/SIGNIFICANCE: The results indicate that cryptic genomic
      rearrangements constitute an important part of the molecular bases of 46,XY DSD
      and that submicroscopic deletions can lead to various types of 46,XY DSD that
      occur as components of contiguous gene deletion syndromes. Most importantly, our
      data provide a novel candidate locus for 46,XY DSD at 20p13.

PMID- 23861872
TI  - Effects of shading on starch pasting characteristics of indica hybrid rice (Oryza
      sativa L.).
AB  - Rice is an important staple crop throughout the world, but environmental stress
      like low-light conditions can negatively impact crop yield and quality. Using pot
      experiments and field experiments, we studied the effects of shading on starch
      pasting viscosity and starch content with six rice varieties for three years,
      using the Rapid Visco Analyser to measure starch pasting viscosity. Shading at
      different growth stages and in different rice varieties all affected the starch
      pasting characteristics of rice. The effects of shading on starch pasting
      viscosity at middle and later growth stages were greater than those at earlier
      stages. Shading enhanced breakdown but reduced hold viscosity and setback at
      tillering-elongation stage. Most pasting parameters changed significantly with
      shading after elongation stage. Furthermore, the responses of different varieties
      to shading differed markedly. The change scope of starch pasting viscosity in
      Dexiang 4103 was rather small after heading, while that in IIyou 498 and Gangyou
      906 was small before heading. We observed clear tendencies in peak viscosity,
      breakdown, and pasting temperature of the five rice varieties with shading in
      2010 and 2011. Correlation analysis indicated that the rice amylose content was
      negatively correlated with breakdown, but was positively correlated with setback.
      Based on our results, IIyou 498, Gangyou 906, and Dexiang 4103 had higher shade
      endurance, making these varieties most suitable for high-quality rice cultivation
      in low-light regions. 

PMID- 23861873
TI  - Detection of Escherichia coli and associated beta-lactamases genes from diabetic
      foot ulcers by multiplex PCR and molecular modeling and docking of SHV-1, TEM-1,
      and OXA-1 beta-lactamases with clindamycin and piperacillin-tazobactam.
AB  - Diabetic foot ulcer (DFU) is a common and devastating complication in diabetes.
      Antimicrobial resistance mediated by extended-spectrum beta-lactamases (ESBLs)
      production by bacteria is considered to be a major threat for foot amputation.
      The present study deals with the detection of Escherichia coli and the prevalence
      of bla(TEM), bla(SHV) and bla(OXA) genes directly from biopsy and swab of foot
      ulcers of diabetic patients. In total, 116 DFU patients were screened, of which
      42 suffering with severe DFUs were selected for this study. Altogether 16 E. coli
      strains were successfully isolated from biopsy and/or swab samples of 15 (35.71%)
      patients. ESBL production was noted in 12 (75%) strains. Amplification of beta
      lactamase genes by multiplex PCR showed the presence of bla(CTX-M) like genes in
      10 strains, bla(TEM) and bla(OXA) in 9 strains each, and bla(SHV) in 8 of the
      total 16 strains of E. coli. Out of the ten antibiotics tested, E. coli strains
      were found to be resistant to ampicillin (75%), cefoxitin (56.25%), cefazolin
      (50%), meropenem (37.5%), cefoperazone (25%), cefepime (31.25%), ceftazidime
      (56.25%), and cefotaxime (68.75%) but all showed sensitivity (100%) to
      clindamycin and piperacillin-tazobactam. 3D models of the most prevalent variants
      of beta-lactamases namely TEM-1, SHV-1, OXA-1, and ESBL namely CTX-M-15 were
      predicted and docking was performed with clindamycin and piperacillin-tazobactam
      to reveal the molecular basis of drug sensitivity. Docking showed the best
      docking score with significant interactions, forming hydrogen bond, Van der Waals
      and polar level interaction with active site residues. Findings of the present
      study may provide useful insights for the development of new antibiotic drugs and
      may also prevent ESBLs-mediated resistance problem in DFU. The novel multiplex
      PCR assay designed in this study may be routinely used in clinical diagnostics of
      E. coli and associated bla(TEM), bla(SHV), and bla(OXA) like genes.

PMID- 23861874
TI  - Decreased leukocyte telomere length (LTL) is associated with stroke but unlikely
      to be causative.
AB  - AIMS: Interindividual variability in telomere length is highly heritable.
      Leukocyte telomere length (LTL) shortening has been shown to be associated with
      the process of atherosclerosis. But whether the inheritance of LTL is related to
      stroke is still unclear. The aim of this study was to test if telomere shortening
      was associated with stroke and whether this association was mainly due to
      inheritance or acquired cardiovascular risk factors. METHODS: Our study was
      focused on stroke in patients and their siblings. 450 subjects were recruited
      into this study: 150 patients with ischemic stroke as case group, 150 siblings of
      patients free of stroke (sibling group) and 150 healthy people as normal control.
      LTL was measured by real-time Polymerase Chain Reactions. The association between
      LTL and the cardiovascular risk factors was also determined. RESULTS: A
      significant decrease of LTL was found in case group when comparing with sibling
      (0.92+/-0.77 vs 1.68+/-1.24, p<0.001) and normal groups (0.92+/-0.77 vs 1.95+/
      1.07, p<0.001), but no significant difference was found between sibling group and
      healthy control (p = 0.330). Shorter telomere length was independently associated
      with hypertension (p = 0.029, OR = 2.189, 95%CI:1.084-4.421), recent social
      pressure (p = 0.001, OR = 3.121, 95%CI:1.597-6.101), age (p = 0.004, OR = 1.055,
      95%CI:1.017-1.093), HDL (p = 0.022, OR = 0.227, 95%CI:0.064-0.810) and diabetes
      (p = 0.018, OR = 3.174, 95%CI:1.221-8.252). Additionally, shortened length of
      telomere (p = 0.017, OR = 3.996, 95%CI:1.283-12.774) was an independent risk
      biomarker for stroke among case and sibling groups. CONCLUSION: The present study
      has demonstrated that decreased LTL might be associated with ischemic stroke but
      unlikely to be causative.

PMID- 23861875
TI  - Developmental adaptation of central nervous system to extremely high
      acetylcholine levels.
AB  - Acetylcholinesterase (AChE) is a key enzyme in termination of fast cholinergic
      transmission. In brain, acetylcholine (ACh) is produced by cholinergic neurons
      and released in extracellular space where it is cleaved by AChE anchored by
      protein PRiMA. Recently, we showed that the lack of AChE in brain of PRiMA knock
      out (KO) mouse increased ACh levels 200-300 times. The PRiMA KO mice adapt nearly
      completely by the reduction of muscarinic receptor (MR) density. Here we
      investigated changes in MR density, AChE, butyrylcholinesterase (BChE) activity
      in brain in order to determine developmental period responsible for such
      adaptation. Brains were studied at embryonal day 18.5 and postnatal days (pd) 0,
      9, 30, 120, and 425. We found that the AChE activity in PRiMA KO mice remained
      very low at all studied ages while in wild type (WT) mice it gradually increased
      till pd120. BChE activity in WT mice gradually decreased until pd9 and then
      increased by pd120, it continually decreased in KO mice till pd30 and remained
      unchanged thereafter. MR number increased in WT mice till pd120 and then became
      stable. Similarly, MR increased in PRiMA KO mice till pd30 and then remained
      stable, but the maximal level reached is approximately 50% of WT mice. Therefore,
      we provide the evidence that adaptive changes in MR happen up to pd30. This is
      new phenomenon that could contribute to the explanation of survival and nearly
      unchanged phenotype of PRiMA KO mice. 

PMID- 23861876
TI  - Single cell gene profiling revealed heterogeneity of paracrine effects of bone
      marrow cells in mouse infarcted hearts.
AB  - It is now recognized that transplantation of bone marrow cells (BMCs) into
      infarcted hearts has the capacity to improve the cardiac function through
      paracrine effects. However, detailed expression levels of paracrine factors in
      BMCs in infarcted hearts are poorly described. By use of laser capture
      microdissection combined with real-time PCR, we depicted the expression profiles
      of paracrine factors in infarcted hearts versus normal hearts. Consistent with
      the in vivo observation, a similar expression pattern was evidenced in cultured
      BMCs. Furthermore, BMCs displayed heterogeneity of paracrine effects in infarcted
      hearts as analyzed at the single cell level using single cell PCR. Interestingly,
      the CD45(+) subpopulation showed higher expression levels of angiogenic factors
      compared to other subpopulations. Finally, most angiogenic factors were induced
      under the microenvironment of infarction. Our study demonstrated the
      heterogeneity of paracrine effects in BMCs at single cell level in infarcted
      hearts, highlighting preferential expression of angiogenic factors in the CD45(+)
      subpopulation. These findings broaden our understanding of paracrine effects of
      BMCs in vivo, and offer new insights into BMCs therapy in myocardial infarction
      (MI). 

PMID- 23861877
TI  - Rapamycin treatment improves neuron viability in an in vitro model of stroke.
AB  - Ischemic stroke is the leading cause of serious, long-term adult disability and
      is associated with sensorimotor and cognitive impairments due to neuronal
      degeneration. Currently, recombinant tissue plasminogen activator (rTPA) is the
      only FDA-approved medical therapy for treatment of patients with acute ischemic
      stroke. However, rTPA can only be given within 3 hours of symptom onset, and only
      2% of patients are eligible. Therefore, there is an urgent need for novel
      neuroprotective treatment options for ischemic stroke. An emerging treatment for
      a diverse range of neurological disorders associated with neurodegeneration is
      rapamycin, a key modulator of the mammalian target of rapamycin (mTOR) pathway.
      The mTOR pathway is the primary regulator of the cellular response to nutrient
      availability, changes in energy status and stress as seen following ischemia and
      reperfusion. However, rapamycin's effects on mTORC1 and mTORC2 are poorly
      understood in neurons. In the current study we show that rapamycin can prevent
      the activation of both mTORC1 and mTORC2 in cortical neurons and improve cell
      survival following oxygen glucose deprivation (OGD), an in vitro model of
      ischemic stroke. This work further supports the investigation of rapamycin as a
      novel neuroprotectant for ischemic stroke. 

PMID- 23861878
TI  - Species delimitation and morphological divergence in the scorpion Centruroides
      vittatus (Say, 1821): insights from phylogeography.
AB  - Scorpion systematics and taxonomy have recently shown a need for revision,
      partially due to insights from molecular techniques. Scorpion taxonomy has been
      difficult with morphological characters as disagreement exists among researchers
      with character choice for adequate species delimitation in taxonomic studies.
      Within the family Buthidae, species identification and delimitation is
      particularly difficult due to the morphological similarity among species and
      extensive intraspecific morphological diversity. The genus Centruroides in the
      western hemisphere is a prime example of the difficulty in untangling the
      taxonomic complexity within buthid scorpions. In this paper, we present
      phylogeographic, Ecological Niche Modeling, and morphometric analyses to further
      understand how population diversification may have produced morphological
      diversity in Centruroides vittatus (Say, 1821). We show that C. vittatus
      populations in the Big Bend and Trans-Pecos region of Texas, USA are
      phylogeographically distinct and may predate the Last Glacial Maximum (LGM). In
      addition, we suggest the extended isolation of Big Bend region populations may
      have created the C. vittatus variant once known as C. pantheriensis. 

PMID- 23861879
TI  - Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFbeta
      mediated axonogenesis.
AB  - The deubiquitylating enzyme Usp9x is highly expressed in the developing mouse
      brain, and increased Usp9x expression enhances the self-renewal of neural
      progenitors in vitro. USP9X is a candidate gene for human neurodevelopmental
      disorders, including lissencephaly, epilepsy and X-linked intellectual
      disability. To determine if Usp9x is critical to mammalian brain development we
      conditionally deleted the gene from neural progenitors, and their subsequent
      progeny. Mating Usp9x(loxP/loxP) mice with mice expressing Cre recombinase from
      the Nestin promoter deleted Usp9x throughout the entire brain, and resulted in
      early postnatal lethality. Although the overall brain architecture was intact,
      loss of Usp9x disrupted the cellular organization of the ventricular and sub
      ventricular zones, and cortical plate. Usp9x absence also led to dramatic
      reductions in axonal length, in vivo and in vitro, which could in part be
      explained by a failure in Tgf-beta signaling. Deletion of Usp9x from the dorsal
      telencephalon only, by mating with Emx1-cre mice, was compatible with survival to
      adulthood but resulted in reduction or loss of the corpus callosum, a dramatic
      decrease in hippocampal size, and disorganization of the hippocampal CA3 region.
      This latter phenotypic aspect resembled that observed in Doublecortin knock-out
      mice, which is an Usp9x interacting protein. This study establishes that Usp9x is
      critical for several aspects of CNS development, and suggests that its regulation
      of Tgf-beta signaling extends to neurons. 

PMID- 23861880
TI  - Association of CD247 polymorphisms with rheumatoid arthritis: a replication study
      and a meta-analysis.
AB  - Given the role of CD247 in the response of the T cells, its entailment in
      autoimmune diseases and in order to better clarify the role of this gene in RA
      susceptibility, we aimed to analyze CD247 gene variants previously associated
      with other autoimmune diseases (rs1052237, rs2056626 and rs864537) in a large
      independent European Caucasian population. However, no evidence of association
      was found for the analyzed CD247 single-nucleotide polymorphisms (SNPs) with RA
      and with the presence/absence of anti-cyclic citrullinated polypeptide. We
      performed a meta-analysis including previously published GWAS data from the
      rs864537 variant, revealing an overall genome-wide significant association
      between this CD247 SNP and RA with anti-CCP (OR = 0.90, CI 95% = 0.87-0.93,
      Poverall = 2.1*10(-10)). Our results show for first time a GWAS-level association
      between this CD247 polymorphism and RA risk. 

PMID- 23861881
TI  - miR-1915 and miR-1225-5p regulate the expression of CD133, PAX2 and TLR2 in adult
      renal progenitor cells.
AB  - Adult renal progenitor cells (ARPCs) were recently identified in the cortex of
      the renal parenchyma and it was demonstrated that they were positive for PAX2,
      CD133, CD24 and exhibited multipotent differentiation ability. Recent studies on
      stem cells indicated that microRNAs (miRNAs), a class of noncoding small RNAs
      that participate in the regulation of gene expression, may play a key role in
      stem cell self-renewal and differentiation. Distinct sets of miRNAs are
      specifically expressed in pluripotent stem cells but not in adult tissues,
      suggesting a role for miRNAs in stem cell self-renewal. We compared miRNA
      expression profiles of ARPCs with that of mesenchymal stem cells (MSCs) and renal
      proximal tubular cells (RPTECs) finding distinct sets of miRNAs that were
      specifically expressed in ARPCs. In particular, miR-1915 and miR-1225-5p
      regulated the expression of important markers of renal progenitors, such as CD133
      and PAX2, and important genes involved in the repair mechanisms of ARPCs, such as
      TLR2. We demonstrated that the expression of both the renal stem cell markers
      CD133 and PAX2 depends on lower miR-1915 levels and that the increase of miR-1915
      levels improved capacity of ARPCs to differentiate into adipocyte-like and
      epithelial-like cells. Finally, we found that the low levels of miR-1225-5p were
      responsible for high TLR2 expression in ARPCs. Therefore, together, miR-1915 and
      miR-1225-5p seem to regulate important traits of renal progenitors: the stemness
      and the repair capacity. 

PMID- 23861882
TI  - UV-induced nuclear import of XPA is mediated by importin-alpha4 in an ATR
      dependent manner.
AB  - Xeroderma pigmentosum Group A (XPA) is a crucial factor in mammalian nucleotide
      excision repair (NER) and nuclear import of XPA from the cytoplasm for NER is
      regulated in cellular DNA damage responses in S-phase. In this study, experiments
      were carried out to determine the transport mechanisms that are responsible for
      the UV (ultraviolet)-induced nuclear import of XPA. We found that, in addition to
      the nuclear localization signal (NLS) of XPA, importin-alpha4 or/and importin
      alpha7 are required for the XPA nuclear import. Further investigation indicated
      that, importin-alpha4 and importin-alpha7 directly interacted with XPA in cells.
      Interestingly, the binding of importin-alpha4 to XPA was dependent on UV
      irradiation, while the binding of importin-alpha7 was not, suggesting a role for
      importin-alpha7 in nuclear translocation of XPA in the absence of DNA damage,
      perhaps with specificity to certain non-S-phases of the cell-cycle. Consistent
      with the previous report of a dependence of UV-induced XPA nuclear import on
      ataxia telangiectasia and Rad3-related protein (ATR) in S-phase, knockdown of ATR
      reduced the amount of XPA interacting with importin-alpha4. In contrast, the
      GTPase XPA binding protein 1 (XAB1), previously proposed to be required for XPA
      nuclear import, showed no effect on the nuclear import of XPA in our siRNA
      knockdown analysis. In conclusion, our results suggest that upon DNA damage
      transport adaptor importin-alpha4 imports XPA into the nucleus in an ATR
      dependent manner, while XAB1 has no role in this process. In addition, these
      findings reveal a potential new therapeutic target for the sensitization of
      cancer cells to chemotherapy. 

PMID- 23861883
TI  - Antibodies to polymorphic invasion-inhibitory and non-Inhibitory epitopes of
      Plasmodium falciparum apical membrane antigen 1 in human malaria.
AB  - BACKGROUND: Antibodies to P. falciparum apical membrane protein 1 (AMA1) may
      contribute to protective immunity against clinical malaria by inhibiting blood
      stage growth of P. falciparum, and AMA1 is a leading malaria vaccine candidate.
      Currently, there is limited knowledge of the acquisition of strain-specific and
      cross-reactive antibodies to AMA1 in humans, or the acquisition of invasion
      inhibitory antibodies to AMA1. METHODOLOGY/FINDINGS: We examined the acquisition
      of human antibodies to specific polymorphic invasion-inhibitory and non
      inhibitory AMA1 epitopes, defined by the monoclonal antibodies 1F9 and 2C5,
      respectively. Naturally acquired antibodies were measured in cohorts of Kenyan
      children and adults. Antibodies to the invasion-inhibitory 1F9 epitope and non
      inhibitory 2C5 epitope were measured indirectly by competition ELISA. Antibodies
      to the 1F9 and 2C5 epitopes were acquired by children and correlated with
      exposure, and higher antibody levels and prevalence were observed with increasing
      age and with active P. falciparum infection. Of note, the prevalence of
      antibodies to the inhibitory 1F9 epitope was lower than antibodies to AMA1 or the
      2C5 epitope. Antibodies to AMA1 ectodomain, the 1F9 or 2C5 epitopes, or a
      combination of responses, showed some association with protection from P.
      falciparum malaria in a prospective longitudinal study. Furthermore, antibodies
      to the invasion-inhibitory 1F9 epitope were positively correlated with parasite
      growth-inhibitory activity of serum antibodies. CONCLUSIONS/SIGNIFICANCE:
      Individuals acquire antibodies to functional, polymorphic epitopes of AMA1 that
      may contribute to protective immunity, and these findings have implications for
      AMA1 vaccine development. Measuring antibodies to the 1F9 epitope by competition
      ELISA may be a valuable approach to assessing human antibodies with invasion
      inhibitory activity in studies of acquired immunity and vaccine trials of AMA1.

PMID- 23861884
TI  - Gene transfection in high serum levels: case studies with new cholesterol based
      cationic gemini lipids.
AB  - BACKGROUND: Six new cationic gemini lipids based on cholesterol possessing
      different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo
      oxyethylene -(CH2CH2O)n- moieties were synthesized. For comparison the
      corresponding monomeric lipid was also prepared. Each new cationic lipid was
      found to form stable, clear suspensions in aqueous media. METHODOLOGY/PRINCIPAL
      FINDINGS: To understand the nature of the individual lipid aggregates, we have
      studied the aggregation properties using transmission electron microscopy (TEM),
      dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction
      (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of
      the DNA from such lipoplexes using ethidium bromide. These gemini lipids in
      presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed
      significant enhancements in the gene transfection compared to several
      commercially available transfection agents. Cholesterol based gemini having -CH2
      CH2-OH groups at the head and one oxyethylene spacer was found to be the most
      effective lipid, which showed transfection activity even in presence of high
      serum levels (50%) greater than Effectene, one of the potent commercially
      available transfecting agents. Most of these geminis protected plasmid DNA
      remarkably against DNase I in serum, although the degree of stability was found
      to vary with their structural features. CONCLUSIONS/SIGNIFICANCE: -OH groups
      present on the cationic headgroups in combination with oxyethylene linkers on
      cholesterol based geminis, gave an optimized combination of new genera of gemini
      lipids possessing high transfection efficiency even in presence of very high
      percentage of serum. This property makes them preferential transfection reagents
      for possible in vivo studies.

PMID- 23861885
TI  - A synthetic model of human beta-thalassemia erythropoiesis using CD34+ cells from
      healthy adult donors.
AB  - Based upon the lack of clinical samples available for research in many
      laboratories worldwide, a significant gap exists between basic and clinical
      studies of beta-thalassemia major. To bridge this gap, we developed an
      artificially engineered model for human beta thalassemia by knocking down beta
      globin gene and protein expression in cultured CD34+ cells obtained from healthy
      adults. Lentiviral-mediated transduction of beta-globin shRNA (beta-KD) caused
      imbalanced globin chain production. Beta-globin mRNA was reduced by 90% compared
      to controls, while alpha-globin mRNA levels were maintained. HPLC analyses
      revealed a 96% reduction in HbA with only a minor increase in HbF. During the
      terminal phases of differentiation (culture days 14-21), beta-KD cells
      demonstrated increased levels of insoluble alpha-globin, as well as activated
      caspase-3. The majority of the beta-KD cells underwent apoptosis around the
      polychromatophilic stage of maturation. GDF15, a marker of ineffective
      erythropoiesis in humans with thalassemia, was significantly increased in the
      culture supernatants from the beta-KD cells. Knockdown of beta-globin expression
      in cultured primary human erythroblasts provides a robust ex vivo model for beta
      thalassemia. 

PMID- 23861886
TI  - Vagal withdrawal and susceptibility to cardiac arrhythmias in rats with high
      trait aggressiveness.
AB  - Personality characteristics, e.g. aggressiveness, have long been associated with
      an increased risk of cardiac disease. However, the underlying mechanisms remain
      unclear. In this study we used a rodent model for characterizing cardiac
      autonomic modulation in rats that differ widely in their level of aggressive
      behavior. To reach this goal, high-aggressive (HA, n = 10) and non-aggressive
      (NA, n = 10) rats were selected from a population (n = 121) of adult male Wild
      type Groningen rats on the basis of their latency time to attack (ALT, s) a male
      intruder in a resident-intruder test lasting 600 s. In order to obtain
      information on their cardiac autonomic modulation, ECG recordings were
      subsequently obtained via radiotelemetry at rest, during stressful stimuli and
      under autonomic pharmacological manipulations, and analyzed by means of time- and
      frequency-domain indexes of heart rate variability. During resting conditions, HA
      rats (ALT<90 s) displayed reduced heart rate variability, mostly in terms of
      lower vagal modulation compared to NA rats (ALT>600 s). Exposure to stressful
      stimuli (i.e. restraint and psychosocial stress) provoked similar tachycardic
      responses between the two groups. However, under stress conditions HA rats
      displayed a reduced vagal antagonism and an increased incidence of
      tachyarrhythmias compared to NA rats. In addition, beta-adrenergic
      pharmacological stimulation induced a much larger incidence of ventricular
      tachyarrhythmias in HA rats compared to NA counterparts. These findings are
      consistent with the view that high levels of aggressive behavior in rats are
      associated to signs of cardiac autonomic impairment and increased arrhythmogenic
      susceptibility that may predict vulnerability to cardiac morbidity and mortality.

PMID- 23861887
TI  - Sphingosine kinase activity is not required for tumor cell viability.
AB  - Sphingosine kinases (SPHKs) are enzymes that phosphorylate the lipid sphingosine,
      leading to the formation of sphingosine-1-phosphate (S1P). In addition to the
      well established role of extracellular S1P as a mitogen and potent
      chemoattractant, SPHK activity has been postulated to be an important
      intracellular regulator of apoptosis. According to the proposed rheostat theory,
      SPHK activity shifts the intracellular balance from the pro-apoptotic
      sphingolipids ceramide and sphingosine to the mitogenic S1P, thereby determining
      the susceptibility of a cell to apoptotic stress. Despite numerous publications
      with supporting evidence, a clear experimental confirmation of the impact of this
      mechanism on tumor cell viability in vitro and in vivo has been hampered by the
      lack of suitable tool reagents. Utilizing a structure based design approach, we
      developed potent and specific SPHK1/2 inhibitors. These compounds completely
      inhibited intracellular S1P production in human cells and attenuated vascular
      permeability in mice, but did not lead to reduced tumor cell growth in vitro or
      in vivo. In addition, siRNA experiments targeting either SPHK1 or SPHK2 in a
      large panel of cell lines failed to demonstrate any statistically significant
      effects on cell viability. These results show that the SPHK rheostat does not
      play a major role in tumor cell viability, and that SPHKs might not be attractive
      targets for pharmacological intervention in the area of oncology. 

PMID- 23861888
TI  - In vitro and in vivo evaluations of nano-hydroxyapatite/polyamide 66/glass fibre
      (n-HA/PA66/GF) as a novel bioactive bone screw.
AB  - In this study, we prepared nano-hydroxyapatite/polyamide 66/glass fibre (n
      HA/PA66/GF) bioactive bone screws. The microstructure, morphology and coating of
      the screws were characterised, and the adhesion, proliferation and viability of
      MC3T3-E1 cells on n-HA/PA66/GF scaffolds were determined using scanning electron
      microscope, CCK-8 assays and cellular immunofluorescence analysis. The results
      confirmed that n-HA/PA66/GF scaffolds were biocompatible and had no negative
      effect on MC3T3-E1 cells in vitro. To investigate the in vivo biocompatibility,
      internal fixation properties and osteogenesis of the bioactive screws, both n
      HA/PA66/GF screws and metallic screws were used to repair intercondylar femur
      fractures in dogs. General photography, CT examination, micro-CT examination,
      histological staining and biomechanical assays were performed at 4, 8, 12 and 24
      weeks after operation. The n-HA/PA66/GF screws exhibited good biocompatibility,
      high mechanical strength and extensive osteogenesis in the host bone. Moreover,
      24 weeks after implantation, the maximum push-out load of the bioactive screws
      was greater than that of the metallic screws. As shown by their good
      cytocompatibility, excellent biomechanical strength and fast formation and
      ingrowth of new bone, n-HA/PA66/GF screws are thus suitable for orthopaedic
      clinical applications. 

PMID- 23861889
TI  - Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique
      biologic and clinical features.
AB  - Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive
      types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal
      CD4+ T-cell lymphomas with indolent behavior have been described, but are not
      well characterized. We describe morphologic, phenotypic, genomic and clinical
      features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas.
      All patients presented with diarrhea and weight loss and were diagnosed with
      celiac disease refractory to a gluten free diet at referring institutions. Small
      intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina
      propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or
      loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent,
      clonal TCRbeta gene rearrangement products were detected at multiple sites. SNP
      array analysis showed relative genomic stability, early in disease course, and
      non-recurrent genetic abnormalities, but complex changes were seen at disease
      transformation (n = 1). Two patients are alive with persistent disease (4.6 and
      2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to
      bowel perforation related to large cell transformation 11 years post-diagnosis.
      Unique pathobiologic features warrant designation of indolent small intestinal
      CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid
      misdiagnosis as EATL or an inflammatory disorder, especially celiac disease. 

PMID- 23861890
TI  - Cenderitide-eluting film for potential cardiac patch applications.
AB  - Cenderitide, also known as CD-NP, is a designer peptide developed by combining
      native mammalian c-type natriuretic peptide (CNP) and the C-terminus isolated
      from the dendroapis natriuretic peptide (DNP) of the venom from the green mamba.
      In early studies, intravenous and subcutaneous infusion of cenderitide was
      reported to reduce left ventricular (LV) mass and ameliorate cardiac remodelling.
      In this work, biodegradable polymeric films encapsulating CD-NP were developed
      and were investigated for their in vitro release and degradation characteristics.
      Subsequently, the bioactivity of released peptide and its effects on human
      cardiac fibroblast (HCF) were explored. We achieved sustained release from three
      films with low, intermediate and high release profiles for 30 days. Moreover, the
      bioactivity of released peptide was verified from the elevated production of
      cyclic guanosine monophospate (cGMP). The CD-NP released from films was able to
      inhibit the proliferation of hypertrophic HCF as well as suppress DNA synthesis
      in HCF. Furthermore, the sustained delivery from films showed comparable or
      superior suppressive actions on hypertrophic HCF compared to daily infusion of CD
      NP. The results suggest that these films could be used to inhibit fibrosis and
      reduce cardiac remodelling via local delivery as cardiac patches. 

PMID- 23861891
TI  - beta-arrestin2 in infiltrated macrophages inhibits excessive inflammation after
      myocardial infarction.
AB  - Beta-arrestins (beta-arrestin1 and beta-arrestin2) are known as cytosolic
      proteins that mediate desensitization and internalization of activated G protein
      coupled receptors. In addition to these functions, beta-arrestins have been found
      to work as adaptor proteins for intracellular signaling pathways. beta-arrestin1
      and beta-arrestin2 are expressed in the heart and are reported to participate in
      normal cardiac function. However, the physiological and pathological roles of
      beta-arrestin1/2 in myocardial infarction (MI) have not been examined. Here, we
      demonstrate that beta-arrestin2 negatively regulates inflammatory responses of
      macrophages recruited to the infarct area. beta-arrestin2 knockout (KO) mice have
      higher mortality than wild-type (WT) mice after MI. In infarcted hearts, beta
      arrestin2 was strongly expressed in infiltrated macrophages. The production of
      inflammatory cytokines was enhanced in beta-arrestin2 KO mice. In addition, p65
      phosphorylation in the macrophages from the infarcted hearts of beta-arrestin2 KO
      mice was increased in comparison to that of WT mice. These results suggest that
      the infiltrated macrophages of beta-arrestin2 KO mice induce excessive
      inflammation at the infarct area. Furthermore, the inflammation in WT mice
      transplanted with bone marrow cells of beta-arrestin2 KO mice is enhanced by MI,
      which is similar to that in beta-arrestin2 KO mice. In contrast, the inflammation
      after MI in beta-arrestin2 KO mice transplanted with bone marrow cells of WT mice
      is comparable to that in WT mice transplanted with bone marrow cells of WT mice.
      In summary, our present study demonstrates that beta-arrestin2 of infiltrated
      macrophages negatively regulates inflammation in infarcted hearts, thereby
      enhancing inflammation when the beta-arrestin2 gene is knocked out. beta
      arrestin2 plays a protective role in MI-induced inflammation. 

PMID- 23861892
TI  - Atg4b-dependent autophagic flux alleviates Huntington's disease progression.
AB  - The accumulation of aggregated mutant huntingtin (mHtt) inclusion bodies is
      involved in Huntigton's disease (HD) progression. Medium sized-spiny neurons
      (MSNs) in the corpus striatum are highly vulnerable to mHtt aggregate
      accumulation and degeneration, but the mechanisms and pathways involved remain
      elusive. Here we have developed a new model to study MSNs degeneration in the
      context of HD. We produced organotypic cortico-striatal slice cultures (CStS)
      from HD transgenic mice mimicking specific features of HD progression. We then
      show that induction of autophagy using catalytic inhibitors of mTOR prevents MSNs
      degeneration in HD CStS. Furthermore, disrupting autophagic flux by
      overexpressing Atg4b in neurons and slice cultures, accelerated mHtt aggregation
      and neuronal death, suggesting that Atg4b-dependent autophagic flux influences HD
      progression. Under these circumstances induction of autophagy using catalytic
      inhibitors of mTOR was inefficient and did not affect mHtt aggregate accumulation
      and toxicity, indicating that mTOR inhibition alleviates HD progression by
      inducing Atg4b-dependent autophagic flux. These results establish modulators of
      Atg4b-dependent autophagic flux as new potential targets in the treatment of HD. 

PMID- 23861893
TI  - Cell cycle checkpoint abnormalities during dementia: A plausible association with
      the loss of protection against oxidative stress in Alzheimer's disease
      [corrected].
AB  - BACKGROUND: Increasing evidence suggests an association between neuronal cell
      cycle (CCL) events and the processes that underlie neurodegeneration in
      Alzheimer's disease (AD). Elevated levels of oxidative stress markers and
      mitochondrial dysfunction are also among early events in AD. Recent studies have
      reported the role of CCL checkpoint proteins and tumor suppressors, such as ATM
      and p53 in the control of glycolysis and oxidative metabolism in cancer, but
      their involvement in AD remains uncertain. METHODS AND FINDINGS: In this
      postmortem study, we measured gene expression levels of eight CCL checkpoint
      proteins in the superior temporal cortex (STC) of persons with varying severities
      of AD dementia and compare them to those of cognitively normal controls. To
      assess whether the CCL changes associated with cognitive impairment in AD are
      specific to dementia, gene expression of the same proteins was also measured in
      STC of persons with schizophrenia (SZ), which is also characterized by
      mitochondrial dysfunction. The expression of CCL-checkpoint and DNA damage
      response genes: MDM4, ATM and ATR was strongly upregulated and associated with
      progression of dementia (cognitive dementia rating, CDR), appearing as early as
      questionable or mild dementia (CDRs 0.5-1). In addition to gene expression
      changes, the downstream target of ATM-p53 signaling - TIGAR, a p53-inducible
      protein, the activation of which can regulate energy metabolism and protect
      against oxidative stress was progressively decreased as severity of dementia
      evolved, but it was unaffected in subjects with SZ. In contrast to AD, different
      CCL checkpoint proteins, which include p53, CHEK1 and BRCA1 were significantly
      downregulated in SZ. CONCLUSIONS: These results support the activation of an ATM
      signaling and DNA damage response network during the progression of AD dementia,
      while the progressive decrease in the levels of TIGAR suggests loss of protection
      initiated by ATM-p53 signaling against intensifying oxidative stress in AD.

PMID- 23861894
TI  - Immune modulation by different types of beta2->1-fructans is toll-like receptor
      dependent.
AB  - INTRODUCTION: beta2->1-fructans are dietary fibers. Main objectives of this study
      were 1) to demonstrate direct signalling of beta2->1-fructans on immune cells, 2)
      to study whether this is mediated by the pattern recognition receptors Toll-like
      receptors (TLRs) and nucleotide-binding oligomerisation domain-containing
      proteins (NODs), and 3) to relate the observed effects to the chain length
      differences in beta2->1-fructans. METHODS: Four different beta2->1-fructan
      formulations were characterised for their chain length profile. Human peripheral
      blood mononuclear cells (PBMCs) were stimulated in vitro with beta2->1-fructans,
      and production of IL-1Ra, IL-1beta, IL-6, IL-10, IL-12p70, and TNF-alpha was
      analysed. Reporter cells for TLRs and NODs were incubated with beta2->1-fructans
      and analysed for NF-kappaB/AP-1 activation. RESULTS: Cytokine production in human
      PBMCs was dose- and chain length-dependent. Strikingly, short chain enriched
      beta2->1-fructans induced a regulatory cytokine balance compared to long chain
      enriched beta2->1-fructans as measured by IL-10/IL-12 ratios. Activation of
      reporter cells showed that signalling was highly dependent on TLRs and their
      adapter, myeloid differentiation primary response protein 88 (MyD88). In human
      embryonic kidney reporter cells, TLR2 was prominently activated, while TLR4, 5,
      7, 8, and NOD2 were mildly activated. CONCLUSIONS: beta2->1-fructans possess
      direct signalling capacity on human immune cells. By activating primarily TLR2,
      and to a lesser extent TLR4, 5, 7, 8, and NOD2, beta2->1-fructan stimulation
      results in NF-kappaB/AP-1 activation. Chain length of beta2->1-fructans is
      important for the induced activation pattern and IL-10/IL-12 ratios.

PMID- 23861895
TI  - A magnetic bead-based method for concentrating DNA from human urine for
      downstream detection.
AB  - Due to the presence of PCR inhibitors, PCR cannot be used directly on most
      clinical samples, including human urine, without pre-treatment. A magnetic bead
      based strategy is one potential method to collect biomarkers from urine samples
      and separate the biomarkers from PCR inhibitors. In this report, a 1 mL urine
      sample was mixed within the bulb of a transfer pipette containing lyophilized
      nucleic acid-silica adsorption buffer and silica-coated magnetic beads. After
      mixing, the sample was transferred from the pipette bulb to a small diameter
      tube, and captured biomarkers were concentrated using magnetic entrainment of
      beads through pre-arrayed wash solutions separated by small air gaps. Feasibility
      was tested using synthetic segments of the 140 bp tuberculosis IS6110 DNA
      sequence spiked into pooled human urine samples. DNA recovery was evaluated by
      qPCR. Despite the presence of spiked DNA, no DNA was detectable in unextracted
      urine samples, presumably due to the presence of PCR inhibitors. However,
      following extraction with the magnetic bead-based method, we found that ~50% of
      spiked TB DNA was recovered from human urine containing roughly 5*10(3) to
      5*10(8) copies of IS6110 DNA. In addition, the DNA was concentrated approximately
      ten-fold into water. The final concentration of DNA in the eluate was 5*10(6),
      14*10(6), and 8*10(6) copies/uL for 1, 3, and 5 mL urine samples, respectively.
      Lyophilized and freshly prepared reagents within the transfer pipette produced
      similar results, suggesting that long-term storage without refrigeration is
      possible. DNA recovery increased with the length of the spiked DNA segments from
      10+/-0.9% for a 75 bp DNA sequence to 42+/-4% for a 100 bp segment and 58+/-9%
      for a 140 bp segment. The estimated LOD was 77 copies of DNA/uL of urine. The
      strategy presented here provides a simple means to achieve high nucleic acid
      recovery from easily obtained urine samples, which does not contain inhibitors of
      PCR. 

PMID- 23861897
TI  - Emotional voice processing: investigating the role of genetic variation in the
      serotonin transporter across development.
AB  - The ability to effectively respond to emotional information carried in the human
      voice plays a pivotal role for social interactions. We examined how genetic
      factors, especially the serotonin transporter genetic variation (5-HTTLPR),
      affect the neurodynamics of emotional voice processing in infants and adults by
      measuring event-related brain potentials (ERPs). The results revealed that
      infants distinguish between emotions during an early perceptual processing stage,
      whereas adults recognize and evaluate the meaning of emotions during later
      semantic processing stages. While infants do discriminate between emotions, only
      in adults was genetic variation associated with neurophysiological differences in
      how positive and negative emotions are processed in the brain. This suggests that
      genetic association with neurocognitive functions emerges during development,
      emphasizing the role that variation in serotonin plays in the maturation of brain
      systems involved in emotion recognition. 

PMID- 23861896
TI  - The metabotropic glutamate 5 receptor modulates extinction and reinstatement of
      methamphetamine-seeking in mice.
AB  - Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics
      registered to assist addicts in discontinuing use. Glutamatergic dysfunction has
      been implicated in the development and maintenance of addiction. We sought to
      assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in
      behaviours relevant to METH addiction because this receptor has been implicated
      in the actions of other drugs of abuse, including alcohol, cocaine and opiates.
      mGlu5 knockout (KO) mice were tested in intravenous self-administration,
      conditioned place preference and locomotor sensitization. Self-administration of
      sucrose was used to assess the response of KO mice to a natural reward.
      Acquisition and maintenance of self-administration, as well as the motivation to
      self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice
      required more extinction sessions to extinguish the operant response for METH,
      and exhibited an enhanced propensity to reinstate operant responding following
      exposure to drug-associated cues. This phenotype was not present when KO mice
      were tested in an equivalent paradigm assessing operant responding for sucrose.
      Development of conditioned place preference and locomotor sensitization were
      intact in KO mice; however, conditioned hyperactivity to the context previously
      paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5
      in the extinction and reinstatement of METH-seeking, and suggests a role for
      mGlu5 in regulating contextual salience. 

PMID- 23861898
TI  - Differential dependence on host cell glycosaminoglycans for infection of
      epithelial cells by high-risk HPV types.
AB  - Human papillomavirus (HPV) infection is the leading cause of cervical cancer
      world-wide. Here, we show that native HPV particles produced in a differentiated
      epithelium have developed different strategies to infect the host. Using
      biochemical inhibition assays and glycosaminoglycan (GAG)-negative cells, we show
      that of the four most common cancer-causing HPV types, HPV18, HPV31, and HPV45
      are largely dependent on GAGs to initiate infection. In contrast, HPV16 can bind
      and enter through a GAG-independent mechanism. Infections of primary human
      keratinocytes, natural host cells for HPV infections, support our conclusions.
      Further, this renders the different virus types differentially susceptible to
      carrageenan, a microbicide targeting virus entry. Our data demonstrates that
      ordered maturation of papillomavirus particles in a differentiating epithelium
      may alter the virus entry mechanism. This study should facilitate a better
      understanding of the attachment and infection by the main oncogenic HPV types,
      and development of inhibitors of HPV infection. 

PMID- 23861899
TI  - Increased S-nitrosylation and proteasomal degradation of caspase-3 during
      infection contribute to the persistence of adherent invasive Escherichia coli
      (AIEC) in immune cells.
AB  - Adherent invasive Escherichia coli (AIEC) have been implicated as a causative
      agent of Crohn's disease (CD) due to their isolation from the intestines of CD
      sufferers and their ability to persist in macrophages inducing granulomas. The
      rapid intracellular multiplication of AIEC sets it apart from other enteric
      pathogens such as Salmonella Typhimurium which after limited replication induce
      programmed cell death (PCD). Understanding the response of infected cells to the
      increased AIEC bacterial load and associated metabolic stress may offer insights
      into AIEC pathogenesis and its association with CD. Here we show that AIEC
      persistence within macrophages and dendritic cells is facilitated by increased
      proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and
      active forms of caspase-3, which can inhibit the enzymes activity, is increased
      in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to
      accumulate upon inhibition of the proteasome indicating an additional role for S
      nitrosylation in inducing caspase-3 degradation in a manner independent of
      ubiquitination. In addition to the autophagic genetic defects that are linked to
      CD, this delay in apoptosis mediated in AIEC infected cells through increased
      degradation of caspase-3, may be an essential factor in its prolonged persistence
      in CD patients. 

PMID- 23861900
TI  - Sorting nexin 9 recruits clathrin heavy chain to the mitotic spindle for
      chromosome alignment and segregation.
AB  - Sorting nexin 9 (SNX9) and clathrin heavy chain (CHC) each have roles in mitosis
      during metaphase. Since the two proteins directly interact for their other
      cellular function in endocytosis we investigated whether they also interact for
      metaphase and operate on the same pathway. We report that SNX9 and CHC
      functionally interact during metaphase in a specific molecular pathway that
      contributes to stabilization of mitotic spindle kinetochore (K)-fibres for
      chromosome alignment and segregation. This function is independent of their
      endocytic role. SNX9 residues in the clathrin-binding low complexity domain are
      required for CHC association and for targeting both CHC and transforming acidic
      coiled-coil protein 3 (TACC3) to the mitotic spindle. Mutation of these sites to
      serine increases the metaphase plate width, indicating inefficient chromosome
      congression. Therefore SNX9 and CHC function in the same molecular pathway for
      chromosome alignment and segregation, which is dependent on their direct
      association. 

PMID- 23861901
TI  - The polyphenol fisetin protects bone by repressing NF-kappaB and MKP-1-dependent
      signaling pathways in osteoclasts.
AB  - Osteoporosis is a bone pathology leading to increase fractures risk and
      challenging quality of life. Since current treatments could exhibit deleterious
      side effects, the use of food compounds derived from plants represents a
      promising innovative alternative due to their potential therapeutic and
      preventive activities against human diseases. In this study, we investigated the
      ability of the polyphenol fisetin to counter osteoporosis and analyzed the
      cellular and molecular mechanisms involved. In vivo, fisetin consumption
      significantly prevented bone loss in estrogen deficiency and inflammation mice
      osteoporosis models. Indeed, bone mineral density, micro-architecture parameters
      and bone markers were positively modulated by fisetin. Consistent with in vivo
      results, we showed that fisetin represses RANKL-induced osteoclast
      differentiation and activity as demonstrated by an inhibition of multinucleated
      cells formation, TRAP activity and differentiation genes expression. The
      signaling pathways NF-kappaB, p38 MAPK, JNK and the key transcription factors c
      Fos and NFATc1 expressions induced by RANKL, were negatively regulated by
      fisetin. We further showed that fisetin inhibits the constitutive proteasomal
      degradation of MKP-1, the phosphatase that deactivates p38 and JNK. Consistently,
      using shRNA stable cell lines, we demonstrated that impairment of MKP-1 decreases
      fisetin potency. Taken together, these results strongly support that fisetin
      should be further considered as a bone protective agent. 

PMID- 23861902
TI  - Why has the number of scientific retractions increased?
AB  - BACKGROUND: The number of retracted scientific publications has risen sharply,
      but it is unclear whether this reflects an increase in publication of flawed
      articles or an increase in the rate at which flawed articles are withdrawn.
      METHODS AND FINDINGS: We examined the interval between publication and retraction
      for 2,047 retracted articles indexed in PubMed. Time-to-retraction (from
      publication of article to publication of retraction) averaged 32.91 months. Among
      714 retracted articles published in or before 2002, retraction required 49.82
      months; among 1,333 retracted articles published after 2002, retraction required
      23.82 months (p<0.0001). This suggests that journals are retracting papers more
      quickly than in the past, although recent articles requiring retraction may not
      have been recognized yet. To test the hypothesis that time-to-retraction is
      shorter for articles that receive careful scrutiny, time-to-retraction was
      correlated with journal impact factor (IF). Time-to-retraction was significantly
      shorter for high-IF journals, but only ~1% of the variance in time-to-retraction
      was explained by increased scrutiny. The first article retracted for plagiarism
      was published in 1979 and the first for duplicate publication in 1990, showing
      that articles are now retracted for reasons not cited in the past. The
      proportional impact of authors with multiple retractions was greater in 1972-1992
      than in the current era (p<0.001). From 1972-1992, 46.0% of retracted papers were
      written by authors with a single retraction; from 1993 to 2012, 63.1% of
      retracted papers were written by single-retraction authors (p<0.001).
      CONCLUSIONS: The increase in retracted articles appears to reflect changes in the
      behavior of both authors and institutions. Lower barriers to publication of
      flawed articles are seen in the increase in number and proportion of retractions
      by authors with a single retraction. Lower barriers to retraction are apparent in
      an increase in retraction for "new" offenses such as plagiarism and a decrease in
      the time-to-retraction of flawed work.

PMID- 23861903
TI  - When kinesthesia becomes visual: a theoretical justification for executing motor
      tasks in visual space.
AB  - Several experimental studies in the literature have shown that even when
      performing purely kinesthetic tasks, such as reaching for a kinesthetically felt
      target with a hidden hand, the brain reconstructs a visual representation of the
      movement. In our previous studies, however, we did not observe any role of a
      visual representation of the movement in a purely kinesthetic task. This apparent
      contradiction could be related to a fundamental difference between the studied
      tasks. In our study subjects used the same hand to both feel the target and to
      perform the movement, whereas in most other studies, pointing to a kinesthetic
      target consisted of pointing with one hand to the finger of the other, or to some
      other body part. We hypothesize, therefore, that it is the necessity of
      performing inter-limb transformations that induces a visual representation of
      purely kinesthetic tasks. To test this hypothesis we asked subjects to perform
      the same purely kinesthetic task in two conditions: INTRA and INTER. In the
      former they used the right hand to both perceive the target and to reproduce its
      orientation. In the latter, subjects perceived the target with the left hand and
      responded with the right. To quantify the use of a visual representation of the
      movement we measured deviations induced by an imperceptible conflict that was
      generated between visual and kinesthetic reference frames. Our hypothesis was
      confirmed by the observed deviations of responses due to the conflict in the
      INTER, but not in the INTRA, condition. To reconcile these observations with
      recent theories of sensori-motor integration based on maximum likelihood
      estimation, we propose here a new model formulation that explicitly considers the
      effects of covariance between sensory signals that are directly available and
      internal representations that are 'reconstructed' from those inputs through
      sensori-motor transformations. 

PMID- 23861904
TI  - Exosomal signaling during hypoxia mediates microvascular endothelial cell
      migration and vasculogenesis.
AB  - Vasculogenesis and angiogenesis are critical processes in fetal circulation and
      placental vasculature development. Placental mesenchymal stem cells (pMSC) are
      known to release paracrine factors (some of which are contained within exosomes)
      that promote angiogenesis and cell migration. The aims of this study were: to
      determine the effects of oxygen tension on the release of exosomes from pMSC; and
      to establish the effects of pMSC-derived exosomes on the migration and angiogenic
      tube formation of placental microvascular endothelial cells (hPMEC). pMSC were
      isolated from placental villi (8-12 weeks of gestation, n = 6) and cultured under
      an atmosphere of 1%, 3% or 8% O2. Cell-conditioned media were collected and
      exosomes (exo-pMSC) isolated by differential and buoyant density centrifugation.
      The dose effect (5-20 ug exosomal protein/ml) of pMSC-derived exosomes on hPMEC
      migration and tube formation were established using a real-time, live-cell
      imaging system (IncucyteTM). The exosome pellet was resuspended in PBS and
      protein content was established by mass spectrometry (MS). Protein function and
      canonical pathways were identified using the PANTHER program and Ingenuity
      Pathway Analysis, respectively. Exo-pMSC were identified, by electron microscopy,
      as spherical vesicles, with a typical cup-shape and diameters around of 100 nm
      and positive for exosome markers: CD63, CD9 and CD81. Under hypoxic conditions
      (1% and 3% O2) exo-pMSC released increased by 3.3 and 6.7 folds, respectively,
      when compared to the controls (8% O2; p<0.01). Exo-pMSC increased hPMEC migration
      by 1.6 fold compared to the control (p<0.05) and increased hPMEC tube formation
      by 7.2 fold (p<0.05). MS analysis identified 390 different proteins involved in
      cytoskeleton organization, development, immunomodulatory, and cell-to-cell
      communication. The data obtained support the hypothesis that pMSC-derived
      exosomes may contribute to placental vascular adaptation to low oxygen tension
      under both physiological and pathological conditions. 

PMID- 23861905
TI  - Post-integration silencing of piggyBac transposable elements in Aedes aegypti.
AB  - The piggyBac transposon, originating in the genome of the Lepidoptera
      Trichoplusia ni, has a broad host range, making it useful for the development of
      a number of transposon-based functional genomic technologies including gene
      vectors, enhancer-, gene- and protein-traps. While capable of being used as a
      vector for the creation of transgenic insects and insect cell lines, piggyBac has
      very limited mobility once integrated into the genome of the yellow fever
      mosquito, Aedes aegypti. A transgenic Aedes aegypti cell line (AagPB8) was
      created containing three integrated piggyBac elements and the remobilization
      potential of the elements was tested. The integrated piggyBac elements in AagPB8
      were transpositionally silent in the presence of functional transposase, which
      was shown to be capable of catalyzing the movement of plasmid-borne piggyBac
      elements in the same cells. The structural integrity of one of the integrated
      elements along with the quality of element-flanking DNA, which is known to
      influence transposition rates, were tested in D. melanogaster. The element was
      found to be structurally intact, capable of transposition and excision in the
      soma and germ-line of Drosophila melanogaster, and in a DNA sequence context
      highly conducive to element movement in Drosophila melanogaster. These data show
      that transpositional silencing of integrated piggyBac elements in the genome of
      Aedes aegypti appears to be a function of higher scale genome organization or
      perhaps epigenetic factors, and not due to structural defects or suboptimal
      integration sites. 

PMID- 23861906
TI  - The dynamics of connexin expression, degradation and localisation are regulated
      by gonadotropins during the early stages of in vitro maturation of swine oocytes.
AB  - Gap junctional communication (GJC) plays a primordial role in oocyte maturation
      and meiotic resumption in mammals by directing the transfer of numerous molecules
      between cumulus cells and the oocyte. Gap junctions are made of connexins (Cx),
      proteins that regulate GJC in numerous ways. Understanding the dynamic regulation
      of connexin arrangements during in vitro maturation (IVM) could provide a
      powerful tool for controlling meiotic resumption and consequently in vitro
      development of fully competent oocytes. However, physiological events happening
      during the early hours of IVM may still be elucidated. The present study reports
      the dynamic regulation of connexin expression, degradation and localization
      during this stage. Cx43, Cx45 and Cx60 were identified as the main connexins
      expressed in swine COC. Cx43 and Cx45 transcripts were judged too static to be a
      regulator of GJC, while Cx43 protein expression was highly responsive to
      gonadotropins, suggesting that it might be the principal regulator of GJC. In
      addition, the degradation of Cx43 expressed after 4.5 h of IVM in response to
      equine chorionic gonadotropin appeared to involve the proteasomal complex. Cx43
      localisation appeared to be associated with GJC. Taken together, these results
      show for the first time that gonadotropins regulate Cx43 protein expression,
      degradation and localisation in porcine COC during the first several hours of
      IVM. Regulation of Cx43 may in turn, via GJC, participate in the development of
      fully competent oocytes. 

PMID- 23861908
TI  - Protective effect of Polygonum orientale L. extracts against Clavibater
      michiganense subsp. sepedonicum, the causal agent of bacterial ring rot of
      potato.
AB  - The Polygonum orientale L. extracts were investigated for antibacterial activity
      against Clavibater michiganense subsp. sepedonicum (Spieckermann & Kotthoff)
      Davis et al., the causal agent of a serious disease called bacterial ring rot of
      potato. The results showed that the leaf extracts of P. orientale had
      significantly (p<0.05) greater antibacterial activity against C. michiganense
      subsp. sepedonicum than root, stem, flower extracts in vitro. According to the
      results of single factor experiments and L(27)3(13) orthogonal experiments,
      optimum extraction conditions were A1B3C1, extraction time 6 h, temperature 80
      degrees C, solid to liquid ratio 1?10 (g:mL). The highest (p<0.05) antibacterial
      activity was observed when pH was 5, excluding the effect of control. The
      extracts were stable under ultraviolet (UV). In vivo analysis revealed that 50
      mg/mL of P. orientale leaf extracts was effective in controlling decay. Under
      field conditions, 50 mg/mL of P. orientale leaf extracts also improved growth
      parameters (whole plant length, shoot length, root length, plant fresh weight,
      shoot fresh weight, root fresh weight, dry weight, and number of leaves), in the
      2010 and 2011 two growing seasons. Further solvent partition assays showed that
      the most active compounds were in the petroleum ether fractionation. Transmission
      electron microscopy (TEM) showed drastic ultrastructural changes caused by
      petroleum ether fractionation, including bacterial deformation, electron-dense
      particles, formation of vacuoles and lack of cytoplasmic materials. These results
      indicated that P. orientale extracts have strong antibacterial activity against
      C. michiganense subsp. sepedonicum and a promising effect in control of bacterial
      ring rot of potato disease.

PMID- 23861907
TI  - Integrating circadian activity and gene expression profiles to predict
      chronotoxicity of Drosophila suzukii response to insecticides.
AB  - Native to Southeast Asia, Drosophila suzukii (Matsumura) is a recent invader that
      infests intact ripe and ripening fruit, leading to significant crop losses in the
      U.S., Canada, and Europe. Since current D. suzukii management strategies rely
      heavily on insecticide usage and insecticide detoxification gene expression is
      under circadian regulation in the closely related Drosophila melanogaster, we set
      out to determine if integrative analysis of daily activity patterns and
      detoxification gene expression can predict chronotoxicity of D. suzukii to
      insecticides. Locomotor assays were performed under conditions that approximate a
      typical summer or winter day in Watsonville, California, where D. suzukii was
      first detected in North America. As expected, daily activity patterns of D.
      suzukii appeared quite different between 'summer' and 'winter' conditions due to
      differences in photoperiod and temperature. In the 'summer', D. suzukii assumed a
      more bimodal activity pattern, with maximum activity occurring at dawn and dusk.
      In the 'winter', activity was unimodal and restricted to the warmest part of the
      circadian cycle. Expression analysis of six detoxification genes and acute
      contact bioassays were performed at multiple circadian times, but only in
      conditions approximating Watsonville summer, the cropping season, when most
      insecticide applications occur. Five of the genes tested exhibited rhythmic
      expression, with the majority showing peak expression at dawn (ZT0, 6am). We
      observed significant differences in the chronotoxicity of D. suzukii towards
      malathion, with highest susceptibility at ZT0 (6am), corresponding to peak
      expression of cytochrome P450s that may be involved in bioactivation of
      malathion. High activity levels were not found to correlate with high insecticide
      susceptibility as initially hypothesized. Chronobiology and chronotoxicity of D.
      suzukii provide valuable insights for monitoring and control efforts, because
      insect activity as well as insecticide timing and efficacy are crucial
      considerations for pest management. However, field research is necessary for
      extrapolation to agricultural settings. 

PMID- 23861909
TI  - Accurate and precise DNA quantification in the presence of different
      amplification efficiencies using an improved Cy0 method.
AB  - Quantitative real-time PCR represents a highly sensitive and powerful technology
      for the quantification of DNA. Although real-time PCR is well accepted as the
      gold standard in nucleic acid quantification, there is a largely unexplored area
      of experimental conditions that limit the application of the Ct method. As an
      alternative, our research team has recently proposed the Cy0 method, which can
      compensate for small amplification variations among the samples being compared.
      However, when there is a marked decrease in amplification efficiency, the Cy0 is
      impaired, hence determining reaction efficiency is essential to achieve a
      reliable quantification. The proposed improvement in Cy0 is based on the use of
      the kinetic parameters calculated in the curve inflection point to compensate for
      efficiency variations. Three experimental models were used: inhibition of primer
      extension, non-optimal primer annealing and a very small biological sample. In
      all these models, the improved Cy0 method increased quantification accuracy up to
      about 500% without affecting precision. Furthermore, the stability of this
      procedure was enhanced integrating it with the SOD method. In short, the improved
      Cy0 method represents a simple yet powerful approach for reliable DNA
      quantification even in the presence of marked efficiency variations. 

PMID- 23861910
TI  - Alpha-linolenic acid exerts an endothelial protective effect against high glucose
      injury via PI3K/Akt pathway.
AB  - Mounting evidence has indicated that the cardiovascular protective effects of
      dietary alpha-linolenic acid (ALA), but whether ALA exerts an endothelial
      protective effect against high glucose injury and the underlying mechanisms
      remain largely unknown. Streptozocin-induced diabetic rats were randomized
      treated orally for 4 weeks with vehicle (0.01% alcohol) or ALA (500 ug/kg per day
      by gavage). Human umbilical vein endothelial cells (HUVECs) were exposed to high
      glucose (28 mmol/L) stimulation for 48 hours. ALA significantly improved
      concentration-dependent vasorelaxation to ACh in diabetic aortic segments and
      inhibited endothelial inflammation as evidenced by decreased soluble P-selectin
      and intercellular adhesion molecule-1 (ICAM-1) in diabetic rats. Furthermore,
      both P-selectin and ICAM-1 expression were increased significantly in high
      glucose-induced HUVECs, resulting in enhanced neutrophils adhesion to HUVECs
      compared with normal glucose group. Treatment with ALA (50 umol/L) increased Akt
      phosphorylation, attenuated P-selectin and ICAM-1 expressions and thus inhibited
      neutrophils adhesion in HUVECs exposed to high glucose, all of which was blocked
      by the PI3K inhibitors LY294002 and wortmannin. These data indicates that ALA
      inhibits endothelial inflammation and improved endothelial function in STZ
      induced diabetic rats. The anti-adhesive effect of ALA against high glucose
      injury may partially be mediated by the PI3K/Akt pathway. 

PMID- 23861911
TI  - Redox signaling via oxidative inactivation of PTEN modulates pressure-dependent
      myogenic tone in rat middle cerebral arteries.
AB  - The present study examined the level of generation of reactive oxygen species
      (ROS) and roles of inactivation of the phosphatase PTEN and the PI3K/Akt
      signaling pathway in response to an increase in intramural pressure-induced
      myogenic cerebral arterial constriction. Step increases in intraluminal pressure
      of cannulated cerebral arteries induced myogenic constriction and concomitant
      formation of superoxide (O2 (.-)) and its dismutation product hydrogen peroxide
      (H2O2) as determined by fluorescent HPLC analysis, microscopic analysis of
      intensity of dihydroethidium fluorescence and attenuation of pressure-induced
      myogenic constriction by pretreatment with the ROS scavenger 4,hydroxyl-2,2,6,6
      tetramethylpiperidine1-oxyl (tempol) or Mito-tempol or MitoQ in the presence or
      absence of PEG-catalase. An increase in intraluminal pressure induced oxidation
      of PTEN and activation of Akt. Pharmacological inhibition of endogenous PTEN
      activity potentiated pressure-dependent myogenic constriction and caused a
      reduction in NPo of a 238 pS arterial KCa channel current and an increase in
      [Ca(2+)]i level in freshly isolated cerebral arterial muscle cells (CAMCs),
      responses that were attenuated by Inhibition of the PI3K/Akt pathway. These
      findings demonstrate an increase in intraluminal pressure induced increase in ROS
      production triggered redox-sensitive signaling mechanism emanating from the cross
      talk between oxidative inactivation of PTEN and activation of the PI3K/Akt
      signaling pathway that involves in the regulation of pressure-dependent myogenic
      cerebral arterial constriction. 

PMID- 23861912
TI  - Tumor selective hyperthermia induced by short-wave capacitively-coupled RF
      electric-fields.
AB  - There is a renewed interest in developing high-intensity short wave capacitively
      coupled radiofrequency (RF) electric-fields for nanoparticle-mediated tumor
      targeted hyperthermia. However, the direct thermal effects of such high-intensity
      electric-fields (13.56 MHZ, 600 W) on normal and tumor tissues are not completely
      understood. In this study, we investigate the heating behavior and dielectric
      properties of normal mouse tissues and orthotopically-implanted human
      hepatocellular and pancreatic carcinoma xenografts. We note tumor-selective
      hyperthermia (relative to normal mouse tissues) in implanted xenografts that can
      be explained on the basis of differential dielectric properties. Furthermore, we
      demonstrate that repeated RF exposure of tumor-bearing mice can result in
      significant anti-tumor effects compared to control groups without detectable harm
      to normal mouse tissues. 

PMID- 23861913
TI  - Nourseothricin N-acetyl transferase: a positive selection marker for mammalian
      cells.
AB  - Development of Nourseothricin N-acetyl transferase (NAT) as a selection marker
      for mammalian cells is described. Mammalian cells are acutely susceptible to
      Nourseothricin, similar to the widely used drug Puromycin, and NAT allows for
      quick and robust selection of transfected/transduced cells in the presence of
      Nourseothricin. NAT is compatible with other selection markers puromycin,
      hygromycin, neomycin, blasticidin, and is a valuable addition to the repertoire
      of mammalian selection markers. 

PMID- 23861914
TI  - Quantification of the early small-scale fishery in the north-eastern Baltic Sea
      in the late 17th century.
AB  - Historical perspectives on fisheries and related human behaviour provide valuable
      information on fishery resources and their exploitation, helping to more
      appropriately set management targets and determine relevant reference levels. In
      this study we analyse historical fisheries and fish trade at the north-eastern
      Baltic Sea coast in the late 17th century. Local consumption and export together
      amounted to the annual removal of about 200 tonnes of fish from the nearby sea
      and freshwater bodies. The fishery was very diverse and exploited altogether one
      cyclostome and 17 fish species with over 90% of the catch being consumed locally.
      The exported fish consisted almost entirely of high-valued species with Stockholm
      (Sweden) being the most important export destination. Due to rich political
      history and natural features of the region, we suggest that the documented
      evidence of this small-scale fishery should be considered as the first
      quantitative summary of exploitation of aquatic living resources in the region
      and can provide a background for future analyses. 

PMID- 23861915
TI  - Transcriptome/degradome-wide identification of R. glutinosa miRNAs and their
      targets: the role of miRNA activity in the replanting disease.
AB  - Rehmannia glutinosa, a traditional Chinese medicine herb, is unable to grow
      normally in a soil where the same species has recently been cultivated. The
      biological basis of this so called "replanting disease" is unknown, but it may
      involve the action of microRNAs (miRNAs), which are known to be important
      regulators of plant growth and development. High throughput Solexa/Illumina
      sequencing was used to generate a transcript library of the R. glutinosa
      transcriptome and degradome in order to identify possible miRNAs and their
      targets implicated in the replanting disease. A total of 87,665 unigenes and 589
      miRNA families (17 of which have not been identified in plants to date) was
      identified from the libraries made from a first year (FP) and a second year (SP)
      crop. A comparison between the FP and SP miRNAs showed that the abundance of
      eight of the novel and 295 of the known miRNA families differed between the FP
      and SP plants. Sequencing of the degradome sampled from FP and SP plants led to
      the identification of 165 transcript targets of 85 of the differentially abundant
      miRNA families. The interaction of some of these miRNAs with their target(s) is
      likely to form an important part of the molecular basis of the replanting disease
      of R. glutinosa. 

PMID- 23861916
TI  - Action spectra of zebrafish cone photoreceptors.
AB  - Zebrafish is becoming an increasingly popular model in the field of visual
      neuroscience. Although the absorption spectra of its cone photopigments have been
      described, the cone action spectra were still unknown. In this study we report
      the action spectra of the four types of zebrafish cone photoreceptors, determined
      by measuring voltage responses upon light stimulation using whole cell patch
      clamp recordings. A generic template of photopigment absorption spectra was fit
      to the resulting action spectra in order to establish the maximum absorption
      wavelength, the A2-based photopigment contribution and the size of the beta-wave
      of each cone-type. Although in general there is close correspondence between
      zebrafish cone action- and absorbance spectra, our data suggest that in the case
      of MWS- and LWS-cones there is appreciable contribution of A2-based photopigments
      and that the beta-wave for these cones is smaller than expected based on the
      absorption spectra. 

PMID- 23861917
TI  - Low connectivity between Mediterranean marine protected areas: a biophysical
      modeling approach for the dusky grouper Epinephelus marginatus.
AB  - Marine protected areas (MPAs) are major tools to protect biodiversity and sustain
      fisheries. For species with a sedentary adult phase and a dispersive larval
      phase, the effectiveness of MPA networks for population persistence depends on
      connectivity through larval dispersal. However, connectivity patterns between
      MPAs remain largely unknown at large spatial scales. Here, we used a biophysical
      model to evaluate connectivity between MPAs in the Mediterranean Sea, a region of
      extremely rich biodiversity that is currently protected by a system of
      approximately a hundred MPAs. The model was parameterized according to the
      dispersal capacity of the dusky grouper Epinephelus marginatus, an archetypal
      conservation-dependent species, with high economic importance and emblematic in
      the Mediterranean. Using various connectivity metrics and graph theory, we showed
      that Mediterranean MPAs are far from constituting a true, well-connected network.
      On average, each MPA was directly connected to four others and MPAs were
      clustered into several groups. Two MPAs (one in the Balearic Islands and one in
      Sardinia) emerged as crucial nodes for ensuring multi-generational connectivity.
      The high heterogeneity of MPA distribution, with low density in the South-Eastern
      Mediterranean, coupled with a mean dispersal distance of 120 km, leaves about 20%
      of the continental shelf without any larval supply. This low connectivity, here
      demonstrated for a major Mediterranean species, poses new challenges for the
      creation of a future Mediterranean network of well-connected MPAs providing
      recruitment to the whole continental shelf. This issue is even more critical
      given that the expected reduction of pelagic larval duration following sea
      temperature rise will likely decrease connectivity even more. 

PMID- 23861918
TI  - Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via
      VEGF/VEGFR-2 signaling pathway.
AB  - Angiogenesis is crucial for cancer initiation, development and metastasis.
      Identifying natural botanicals targeting angiogenesis has been paid much
      attention for drug discovery in recent years, with the advantage of increased
      safety. Isoliquiritigenin (ISL) is a dietary chalcone-type flavonoid with various
      anti-cancer activities. However, little is known about the anti-angiogenic
      activity of isoliquiritigenin and its underlying mechanisms. Herein, we found
      that ISL significantly inhibited the VEGF-induced proliferation of human
      umbilical vein endothelial cells (HUVECs) at non-toxic concentration. A series of
      angiogenesis processes including tube formation, invasion and migration abilities
      of HUVECs were also interrupted by ISL in vitro. Furthermore, ISL suppressed
      sprout formation from VEGF-treated aortic rings in an ex-vivo model. Molecular
      mechanisms study demonstrated that ISL could significantly inhibit VEGF
      expression in breast cancer cells via promoting HIF-1alpha (Hypoxia inducible
      factor-1alpha) proteasome degradation and directly interacted with VEGFR-2 to
      block its kinase activity. In vivo studies further showed that ISL administration
      could inhibit breast cancer growth and neoangiogenesis accompanying with
      suppressed VEGF/VEGFR-2 signaling, elevated apoptosis ratio and little toxicity
      effects. Molecular docking simulation indicated that ISL could stably form
      hydrogen bonds and aromatic interactions within the ATP-binding region of VEGFR
      2. Taken together, our study shed light on the potential application of ISL as a
      novel natural inhibitor for cancer angiogenesis via the VEGF/VEGFR-2 pathway.
      Future studies of ISL for chemoprevention or chemosensitization against breast
      cancer are thus warranted. 

PMID- 23861919
TI  - In vivo study of transverse carpal ligament stiffness using acoustic radiation
      force impulse (ARFI) imaging.
AB  - The transverse carpal ligament (TCL) forms the volar boundary of the carpal
      tunnel and may provide mechanical constraint to the median nerve, leading to
      carpal tunnel syndrome. Therefore, the mechanical properties of the TCL are
      essential to better understand the etiology of carpal tunnel syndrome. The
      purpose of this study was to investigate the in vivo TCL stiffness using acoustic
      radiation force impulse (ARFI) imaging. The shear wave velocity (SWV) of the TCL
      was measured using Virtual Touch IQ(TM) software in 15 healthy, male subjects.
      The skin and the thenar muscles were also examined as reference tissues. In
      addition, the effects of measurement location and ultrasound transducer
      compression on the SWV were studied. The SWV of the TCL was dependent on the
      tissue location, with greater SWV values within the muscle-attached region than
      those outside of the muscle-attached region. The SWV of the TCL was significantly
      smaller without compression (5.21 +/- 1.08 m/s) than with compression (6.62 +/-
      1.18 m/s). The SWV measurements of the skin and the thenar muscles were also
      affected by transducer compression, but to different extents than the SWV of the
      TCL. Therefore to standardize the ARFI imaging procedure, it is recommended that
      a layer of ultrasound gel be maintained to minimize the effects of tissue
      compression. This study demonstrated the feasibility of ARFI imaging for
      assessing the stiffness characteristics of the TCL in vivo, which has the
      potential to identify pathomechanical changes of the tissue. 

PMID- 23861920
TI  - Determination of minimum training sample size for microarray-based cancer outcome
      prediction-an empirical assessment.
AB  - The promise of microarray technology in providing prediction classifiers for
      cancer outcome estimation has been confirmed by a number of demonstrable
      successes. However, the reliability of prediction results relies heavily on the
      accuracy of statistical parameters involved in classifiers. It cannot be reliably
      estimated with only a small number of training samples. Therefore, it is of vital
      importance to determine the minimum number of training samples and to ensure the
      clinical value of microarrays in cancer outcome prediction. We evaluated the
      impact of training sample size on model performance extensively based on 3 large
      scale cancer microarray datasets provided by the second phase of MicroArray
      Quality Control project (MAQC-II). An SSNR-based (scale of signal-to-noise ratio)
      protocol was proposed in this study for minimum training sample size
      determination. External validation results based on another 3 cancer datasets
      confirmed that the SSNR-based approach could not only determine the minimum
      number of training samples efficiently, but also provide a valuable strategy for
      estimating the underlying performance of classifiers in advance. Once translated
      into clinical routine applications, the SSNR-based protocol would provide great
      convenience in microarray-based cancer outcome prediction in improving classifier
      reliability. 

PMID- 23861921
TI  - Genetic analysis of invasive Aedes albopictus populations in Los Angeles County,
      California and its potential public health impact.
AB  - The Asian tiger mosquito, Aedes albopictus, is an anthropophilic aggressive
      daytime-biting nuisance and an efficient vector of certain arboviruses and
      filarial nematodes. Over the last 30 years, this species has spread rapidly
      through human travel and commerce from its native tropical forests of Asia to
      every continent except Antarctica. In 2011, a population of Asian tiger mosquito
      (Aedes albopictus) was discovered in Los Angeles (LA) County, California. To
      determine the probable origin of this invasive species, the genetic structure of
      the population was compared against 11 populations from the United States and
      abroad, as well as preserved specimens from a 2001 introduction into California
      using the mitochondrial cytochrome c oxidase 1 (CO1) gene. A total of 66
      haplotypes were detected among samples and were divided into three main groups.
      Aedes albopictus collected in 2001 and 2011 from LA County were genetically
      related and similar to those from Asia but distinct from those collected in the
      eastern and southeastern United States. In view of the high genetic similarities
      between the 2001 and 2011 LA samples, it is possible that the 2011 population
      represents in part the descendants of the 2001 introduction. There remains an
      imperative need for improved surveillance and control strategies for this
      species. 

PMID- 23861922
TI  - TARE1, a mutated Copia-like LTR retrotransposon followed by recent massive
      amplification in tomato.
AB  - Long terminal repeat retrotransposons (LTR-RTs) are the major DNA components in
      flowering plants. Most LTR-RTs contain dinucleotides 'TG' and 'CA' at the ends of
      the two LTRs. Here we report the structure, evolution, and propensity of a tomato
      atypical retrotransposon element (TARE1) with both LTRs starting as 'TA'. This
      family is also characterized by high copy numbers (354 copies), short LTR size
      (194 bp), extremely low ratio of solo LTRs to intact elements (0.05?1), recent
      insertion (most within 0.75~1.75 million years, Mys), and enrichment in
      pericentromeric region. The majority (83%) of the TARE1 elements are shared
      between S. lycopersicum and its wild relative S. pimpinellifolium, but none of
      them are found in potato. In the present study, we used shared LTR-RTs as
      molecular markers and estimated the divergence time between S. lycopersicum and
      S. pimpinellifolium to be <0.5 Mys. Phylogenetic analysis showed that the TARE1
      elements, together with two closely related families, TARE2 and TGRE1, have
      formed a sub-lineage belonging to a Copia-like Ale lineage. Although TARE1 and
      TARE2 shared similar structural characteristics, the timing, scale, and activity
      of their amplification were found to be substantially different. We further
      propose a model wherein a single mutation from 'G' to 'A' in 3' LTR followed by
      amplification is responsible for the origin of TARE1, thus providing evidence
      that the proliferation of a spontaneous mutation can be mediated by the
      amplification of LTR-RTs at the level of RNA. 

PMID- 23861923
TI  - The plastid genome of Najas flexilis: adaptation to submersed environments is
      accompanied by the complete loss of the NDH complex in an aquatic angiosperm.
AB  - The re-colonization of aquatic habitats by angiosperms has presented a difficult
      challenge to plants whose long evolutionary history primarily reflects
      adaptations to terrestrial conditions. Many aquatics must complete vital stages
      of their life cycle on the water surface by means of floating or emergent leaves
      and flowers. Only a few species, mainly within the order Alismatales, are able to
      complete all aspects of their life cycle including pollination, entirely
      underwater. Water-pollinated Alismatales include seagrasses and water nymphs
      (Najas), the latter being the only freshwater genus in the family
      Hydrocharitaceae with subsurface water-pollination. We have determined the
      complete nucleotide sequence of the plastid genome of Najas flexilis. The plastid
      genome of N. flexilis is a circular AT-rich DNA molecule of 156 kb, which
      displays a quadripartite structure with two inverted repeats (IR) separating the
      large single copy (LSC) from the small single copy (SSC) regions. In N. flexilis,
      as in other Alismatales, the rps19 and trnH genes are localized in the LSC region
      instead of within the IR regions as in other monocots. However, the N. flexilis
      plastid genome presents some anomalous modifications. The size of the SSC region
      is only one third of that reported for closely related species. The number of
      genes in the plastid is considerably less. Both features are due to loss of the
      eleven ndh genes in the Najas flexilis plastid. In angiosperms, the absence of
      ndh genes has been related mainly to the loss of photosynthetic function in
      parasitic plants. The ndh genes encode the NAD(P)H dehydrogenase complex,
      believed essential in terrestrial environments, where it increases photosynthetic
      efficiency in variable light intensities. The modified structure of the N.
      flexilis plastid genome suggests that adaptation to submersed environments, where
      light is scarce, has involved the loss of the NDH complex in at least some
      photosynthetic angiosperms. 

PMID- 23861924
TI  - Distinct patterns of cerebral extravasation by Evans blue and sodium fluorescein
      in rats.
AB  - The Evans blue dye (EBD; 961 Da) and the sodium fluorescein dye (NaF; 376 Da) are
      commonly used inert tracers in blood-brain barrier (BBB) research. They are both
      highly charged low molecular weight (LMW) tracers with similar lipophobic
      profiles. Nevertheless, the EBD binds to serum albumin (69,000 Da) to become a
      high molecular weight (HMW) protein tracer when injected into the circulation,
      whereas the NaF remains an unbound small molecule in the circulation. In this
      study, rats were injected with equal doses of either EBD or NaF to monitor their
      blood and tissue distribution. The EBD was largely confined to the circulation
      with little accumulation in the peripheral organ and even less accumulation in
      the central tissue, whereas the NaF distributed more evenly between the blood and
      the peripheral organ but was also largely excluded from the central tissue.
      Importantly, the EBD crossed the BBB most effectively at the prefrontal cortex
      and the cerebellum, and most poorly at the striatum. In marked contrast, the NaF
      was evenly distributed throughout the brain. Finally, the EBD exhibited this same
      peculiar tissue distribution profile when administered by either bolus injection
      or slow infusion. Our study suggests that different regions of the brain are
      equally permeable to LMW inert dyes like the NaF, but are markedly different in
      permeability to HMW proteins such as EBD-labelled serum albumin. 

PMID- 23861925
TI  - Three-dimensional imaging of hepatic sinusoids in mice using synchrotron
      radiation micro-computed tomography.
AB  - Hepatic sinusoid, the smallest vessel in the liver, plays important roles in
      hepatic microcirculation. Although the structure of the hepatic sinusoids affects
      diverse functions of the liver, little is known about morphological alterations
      in the sinusoids under pathological conditions. In this study, we show that the
      structure of hepatic sinusoids can be identified three-dimensionally in normal
      and carbon tetrachloride-injured mouse liver, using the absorption mode of
      synchrotron radiation micro-computed tomography. We observed that the hepatic
      sinusoidal structure on tomographic slice images was similar to that on
      histological images of normal and acutely injured mice. Moreover, centrilobular
      necrosis and structural alterations of the sinusoids in the necrotic region were
      detectable on tomographic slice and volume-rendered images of the acutely injured
      mice. Furthermore, quantitative analyses on 3D volume-rendered images of the
      injured sinusoid revealed decrease in the volume of the sinusoid and connectivity
      of the sinusoidal network. Our results suggest that the use of synchrotron
      radiation micro-computed tomography may improve our understanding of the
      pathogenesis of hepatic diseases by detecting the hepatic sinusoids and their
      alterations in three-dimensional structures of the damaged liver. 

PMID- 23861926
TI  - Bioinformatics of recent aqua- and orthoreovirus isolates from fish: evolutionary
      gain or loss of FAST and fiber proteins and taxonomic implications.
AB  - Family Reoviridae, subfamily Spinareovirinae, includes nine current genera. Two
      of these genera, Aquareovirus and Orthoreovirus, comprise members that are
      closely related and consistently share nine homologous proteins. Orthoreoviruses
      have 10 dsRNA genome segments and infect reptiles, birds, and mammals, whereas
      aquareoviruses have 11 dsRNA genome segments and infect fish. Recently, the first
      10-segmented fish reovirus, piscine reovirus (PRV), has been identified and shown
      to be phylogenetically divergent from the 11-segmented viruses constituting genus
      Aquareovirus. We have recently extended results for PRV by showing that it does
      not encode a fusion-associated small transmembrane (FAST) protein, but does
      encode an outer-fiber protein containing a long N-terminal region of predicted
      alpha-helical coiled coil. Three recently characterized 11-segmented fish
      reoviruses, obtained from grass carp in China and sequenced in full, are also
      divergent from the viruses now constituting genus Aquareovirus, though not to the
      same extent as PRV. In the current study, we reexamined the sequences of these
      three recent isolates of grass carp reovirus (GCRV)-HZ08, GD108, and 104-for
      further clues to their evolution relative to other aqua- and orthoreoviruses.
      Structure-based fiber motifs in their encoded outer-fiber proteins were
      characterized, and other bioinformatics analyses provided evidence against the
      presence of a FAST protein among their encoded nonstructural proteins.
      Phylogenetic comparisons showed the combination of more distally branching,
      approved Aquareovirus and Orthoreovirus members, plus more basally branching
      isolates GCRV104, GCRV-HZ08/GD108, and PRV, constituting a larger, monophyletic
      taxon not suitably recognized by the current taxonomic hierarchy. Phylogenetics
      also suggested that the last common ancestor of all these viruses was a fiber
      encoding, nonfusogenic virus and that the FAST protein family arose from at least
      two separate gain-of-function events. In addition, an apparent evolutionary
      correlation was found between the gain or loss of NS-FAST and outer-fiber
      proteins among more distally branching members of this taxon. 

PMID- 23861927
TI  - Effects of sodium butyrate and its synthetic amide derivative on liver
      inflammation and glucose tolerance in an animal model of steatosis induced by
      high fat diet.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common
      form of chronic liver disease. Insulin resistance (IR) appears to be critical in
      its pathogenesis. We evaluated the effects of sodium butyrate (butyrate) and its
      synthetic derivative N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) in a rat
      model of insulin resistance and steatosis induced by high-fat diet (HFD).
      METHODS: After weaning, young male Sprague-Dawley rats were divided into 4 groups
      receiving different diets for 6 weeks: 1. control group (standard diet); 2. HFD;
      3. HFD plus butyrate (20 mg/kg/die) and 4. HFD plus FBA (42.5 mg/Kg/die, the
      equimolecular dose of butyrate). Liver tissues of the rats were analyzed by
      Western blot and real-time PCR. Insulin resistance, liver inflammation and Toll
      like pattern modifications were determined. RESULTS: Evaluation of these two
      preparations of butyrate showed a reduction of liver steatosis and inflammation
      in HFD fed animals. The compounds showed a similar potency in the normalisation
      of several variables, such as transaminases, homeostasis model assessment for
      insulin resistance index, and glucose tolerance. Both treatments significantly
      reduced hepatic TNF-alpha expression and restored GLUTs and PPARs, either in
      liver or adipose tissue. Finally, FBA showed a higher potency in reducing pro
      inflammatory parameters in the liver, via suppression of Toll-like receptors and
      NF-kappaB activation. CONCLUSIONS: Our results demonstrated a protective effect
      of butyrate in limiting molecular events underlying the onset of IR and NAFLD,
      suggesting a potential clinical relevance for this substance. In particular, its
      derivative, FBA, could represent an alternative therapeutic option to sodium
      butyrate, sharing a comparable efficacy, but a better palatability and
      compliance.

PMID- 23861928
TI  - Too few, too weak: conflict of interest policies at Canadian medical schools.
AB  - INTRODUCTION: The education of medical students should be based on the best
      clinical information available, rather than on commercial interests. Previous
      research looking at university-wide conflict of interest (COI) policies used in
      Canadian medical schools has shown very poor regulation. An analysis of COI
      policies was undertaken to document the current policy environment in all 17
      Canadian medical schools. METHODS: A web search was used to initially locate COI
      policies supplemented by additional information from the deans of each medical
      school. Strength of policies was rated on a scale of 0 to 2 in 12 categories and
      also on the presence of enforcement measures. For each school, we report scores
      for all 12 categories, enforcement measures, and summative scores. RESULTS: COI
      policies received summative scores that ranged from 0 to 19, with 0 the lowest
      possible score obtainable and 24 the maximum. The highest mean scores per
      category were for disclosure and ghostwriting (0.9) and for gifts and
      scholarships (0.8). DISCUSSION: This study provides the first comprehensive
      evaluation of all 17 Canadian medical school-specific COI policies. Our results
      suggest that the COI policy environment at Canadian medical schools is generally
      permissive. Policy development is a dynamic process. We therefore encourage all
      Canadian medical schools to develop restrictive COI policies to ensure that their
      medical students are educated based on the best clinical evidence available, free
      of industry biases and COI relationships that may influence the future medical
      thinking and prescribing practices of medical students in Canada once they
      graduate.

PMID- 23861929
TI  - CYP1B1 polymorphisms and susceptibility to prostate cancer: a meta-analysis.
AB  - BACKGROUND: Studies investigating the association between single-nucleotide
      polymorphisms (SNPs) of the cytochrome P450 1B1 (CYP1B1) and prostate cancer
      (PCa) risk report conflicting results. To derive a more precise estimation of the
      relationship between CYP1B1 polymorphisms and PCa risk, a meta-analysis was
      performed. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive literature search was
      conducted to identify all eligible studies of CYP1B1 polymorphisms and PCa risk.
      A total of 14 independent studies, including 6380 cases and 5807 controls, were
      identified. We investigated by meta-analysis the effects of 5 polymorphisms in
      CYP1B1 L432V (12 studies, 5999 cases, 5438 controls), R48G (6 studies, 1647
      cases, 1846 controls), N453S (4 studies, 1407 cases, 1499 controls), -13C/T (4
      studies, 1116 cases, 1114 controls), and A119S (4 studies, 1057 cases, 1018
      controls). There was no evidence that L432V had significant association with PCa
      in overall population. After subgroup analyses by ethnicity, we found that L432V
      was significantly associated with PCa risk in Asians (additive: OR = 2.38, 95%CI
      = 1.31-4.33, P = 0.004; recessive: OR = 2.11, 95%CI = 1.17-3.79, P = 0.01;
      dominant: OR = 1.52, 95%CI = 1.14-2.01, P = 0.004; allelic: OR = 1.52, 95%CI =
      1.20-1.92, P = 0.0006). When stratified by source of controls, significantly
      elevated PCa risk was found in all genetic models in population based studies
      (additive: OR = 1.34, 95%CI = 1.14-1.57, P = 0.0003; recessive: OR = 1.25, 95%CI
      = 1.09-1.43, P = 0.002; dominant: OR = 1.25, 95%CI = 1.11-1.41, P = 0.0002;
      allelic: OR = 1.18, 95%CI = 1.09-1.28, P<0.0001). For N453S, there was a
      significant association between N453S polymorphism and PCa risk in both overall
      population (dominant: OR = 1.18, 95%CI = 1.00-1.38, P = 0.04) and mixed
      population (domiant: OR = 1.31, 95%CI = 1.06-1.63, P = 0.01; allelic: OR = 1.27,
      95%CI = 1.05-1.54, P = 0.01). For A119S, our analysis suggested that A119S was
      associated with PCa risk under recessive model in overall population (OR = 1.37,
      95%CI = 1.04-1.80, P = 0.03). CONCLUSIONS: The results suggest that L432V, N453S,
      and A119S polymorphisms of CYP1B1 might be associated with the susceptibility of
      PCa. Further larger and well-designed multicenter studies are warranted to
      validate these findings.

PMID- 23861930
TI  - Qualitative and quantitative analyses of the echolocation strategies of bats on
      the basis of mathematical modelling and laboratory experiments.
AB  - Prey pursuit by an echolocating bat was studied theoretically and experimentally.
      First, a mathematical model was proposed to describe the flight dynamics of a bat
      and a single prey. In this model, the flight angle of the bat was affected by
      [Formula: see text] angles related to the flight path of the single moving prey,
      that is, the angle from the bat to the prey and the flight angle of the prey.
      Numerical simulation showed that the success rate of prey capture was high, when
      the bat mainly used the angle to the prey to minimize the distance to the prey,
      and also used the flight angle of the prey to minimize the difference in flight
      directions of itself and the prey. Second, parameters in the model were estimated
      according to experimental data obtained from video recordings taken while a
      Japanese horseshoe bat (Rhinolphus derrumequinum nippon) pursued a moving moth
      (Goniocraspidum pryeri) in a flight chamber. One of the estimated parameter
      values, which represents the ratio in the use of the [Formula: see text] angles,
      was consistent with the optimal value of the numerical simulation. This agreement
      between the numerical simulation and parameter estimation suggests that a bat
      chooses an effective flight path for successful prey capture by using the
      [Formula: see text] angles. Finally, the mathematical model was extended to
      include a bat and [Formula: see text] prey. Parameter estimation of the extended
      model based on laboratory experiments revealed the existence of bat's dynamical
      attention towards [Formula: see text] prey, that is, simultaneous pursuit of
      [Formula: see text] prey and selective pursuit of respective prey. Thus, our
      mathematical model contributes not only to quantitative analysis of effective
      foraging, but also to qualitative evaluation of a bat's dynamical flight strategy
      during multiple prey pursuit. 

PMID- 23861931
TI  - Pediatric and youth traffic-collision injuries in Al Ain, United Arab Emirates: a
      prospective study.
AB  - AIM: To study the mechanism of road traffic collisions (RTC), use of safety
      devices, and outcome of hospitalized pediatric and youth RTC injured patients so
      as to give recommendations regarding prevention of pediatric RTC injuries.
      METHODS: All RTC injured children and youth (0-19-year-olds) who were admitted to
      Al Ain City's two major trauma centers or who died after arrival to these centers
      were prospectively studied from April 2006 to October 2007. Demography of
      patients, road-user and vehicle types, crash mechanism, usage of safety devices,
      injured body regions, injury severity, Revised Trauma Score, Glasgow Coma Scale,
      intensive care unit admissions, hospital stay and mortality were analyzed.
      RESULTS: 245 patients were studied, 69% were vehicle occupants, 15% pedestrians,
      9% motorcyclists and 5% bicyclists. 79% were males and 67% UAE citizens. The most
      common mechanism of RTC was rollover of vehicle (37%) followed by front impact
      collision (32%). 32 (13%) of vehicle occupants were ejected from car. 63% of
      ejected occupants and 70% of motorcyclists sustained head injuries. Only 2%
      (3/170) vehicle passengers used seatbelts and 13% (3/23) motorcyclists a helmet.
      CONCLUSIONS: Male drivers and UAE nationals were at high risk of RTC as drivers
      and as motorcyclists. Ejection rate was high because safety restraint use was
      extremely low in our community. More education and law enforcement focusing
      especially on car/booster seat use is needed.

PMID- 23861932
TI  - Iron, hepcidin and inflammatory status of young healthy overweight and obese
      women in Australia.
AB  - BACKGROUND AND AIMS: Evidence suggests obesity-related inflammation alters iron
      metabolism potentially increasing the risk of iron deficiency. This cross
      sectional study aimed to investigate iron, hepcidin and inflammatory status in
      young, healthy overweight and obese women. METHODS: 114 young (18-25 years),
      healthy comorbidity-free women with a body mass index (BMI) >=27.5 kg/m(2) were
      recruited. Biochemical data were analysed using mean +/- standard deviation or
      median (interquartile range) and multivariate modelling. Biochemical markers were
      also stratified according to varying degrees of overweight and obesity. RESULTS:
      Anaemia (haemoglobin <120 g/l) and iron deficiency (serum ferritin <15.0 ug/l)
      were prevalent in 10% and 17% of participants respectively. Mean/median soluble
      transferrin receptor was 1.61+/-0.44 mg/l; hepcidin 6.40 (7.85) ng/ml and C
      reactive protein (CRP) 3.58 (5.81) mg/l. Multivariate modelling showed that BMI
      was a significant predictor of serum iron (coefficient = -0.379; standard error =
      0.139; p = 0.008), transferrin saturation (coefficient = -0.588; standard error =
      0.222; p = 0.009) and CRP (coefficient = 0.127; standard error = 0.024; p<0.001).
      Stratification of participants according to BMI showed those with >=35.0 kg/m(2)
      had significantly higher CRP (p<0.001) than those in lower BMI categories.
      CONCLUSIONS: Increasing obesity was associated with minor disturbances in iron
      metabolism. However, overall outcomes indicated simple iron deficiency
      (hypoferritinaemia) was the primary iron-related abnormality with no apparent
      contribution of inflammation or hepcidin, even in those with BMI >35.0 kg/m(2).
      This indicates that obesity alone may not be sufficient to induce clinically
      significant disturbances to iron metabolism as previously described. This may be
      attributed to the lack of comorbidity in this cohort.

PMID- 23861933
TI  - A sexually conditioned switch of chemosensory behavior in C. elegans.
AB  - In sexually reproducing animals, mating is essential for transmitting genetic
      information to the next generation and therefore animals have evolved mechanisms
      for optimizing the chance of successful mate location. In the soil nematode C.
      elegans, males approach hermaphrodites via the ascaroside pheromones, recognize
      hermaphrodites when their tails contact the hermaphrodites' body, and eventually
      mate with them. These processes are mediated by sensory signals specialized for
      sexual communication, but other mechanisms may also be used to optimize mate
      location. Here we describe associative learning whereby males use sodium chloride
      as a cue for hermaphrodite location. Both males and hermaphrodites normally avoid
      sodium chloride after associative conditioning with salt and starvation. However,
      we found that males become attracted to sodium chloride after conditioning with
      salt and starvation if hermaphrodites are present during conditioning. For this
      conditioning, which we call sexual conditioning, hermaphrodites are detected by
      males through pheromonal signaling and additional cue(s). Sex transformation
      experiments suggest that neuronal sex of males is essential for sexual
      conditioning. Altogether, these results suggest that C. elegans males integrate
      environmental, internal and social signals to determine the optimal strategy for
      mate location. 

PMID- 23861934
TI  - Acute alcohol consumption impairs controlled but not automatic processes in a
      psychophysical pointing paradigm.
AB  - Numerous studies have investigated the effects of alcohol consumption on
      controlled and automatic cognitive processes. Such studies have shown that
      alcohol impairs performance on tasks requiring conscious, intentional control,
      while leaving automatic performance relatively intact. Here, we sought to extend
      these findings to aspects of visuomotor control by investigating the effects of
      alcohol in a visuomotor pointing paradigm that allowed us to separate the
      influence of controlled and automatic processes. Six male participants were
      assigned to an experimental "correction" condition in which they were instructed
      to point at a visual target as quickly and accurately as possible. On a small
      percentage of trials, the target "jumped" to a new location. On these trials, the
      participants' task was to amend their movement such that they pointed to the new
      target location. A second group of 6 participants were assigned to a
      "countermanding" condition, in which they were instructed to terminate their
      movements upon detection of target "jumps". In both the correction and
      countermanding conditions, participants served as their own controls, taking part
      in alcohol and no-alcohol conditions on separate days. Alcohol had no effect on
      participants' ability to correct movements "in flight", but impaired the ability
      to withhold such automatic corrections. Our data support the notion that alcohol
      selectively impairs controlled processes in the visuomotor domain. 

PMID- 23861935
TI  - Innate immune receptors in human airway smooth muscle cells: activation by
      TLR1/2, TLR3, TLR4, TLR7 and NOD1 agonists.
AB  - BACKGROUND: Pattern-recognition receptors (PRRs), including Toll-like receptors
      (TLRs), NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs), recognize
      microbial components and trigger a host defense response. Respiratory tract
      infections are common causes of asthma exacerbations, suggesting a role for PRRs
      in this process. The present study aimed to examine the expression and function
      of PRRs on human airway smooth muscle cells (HASMCs). METHODS: Expression of TLR,
      NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow
      cytometry and immunocytochemistry. The functional responses to ligand stimulation
      were investigated in terms of cytokine and chemokine release, cell surface marker
      expression, proliferation and proteins regulating the contractile state. RESULTS:
      HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the
      corresponding agonists Pam3CSK4, poly(I:C), LPS, R-837 and iE-DAP, respectively,
      induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR,
      while poly(I:C) also affected the release of eotaxin and RANTES. The
      proliferative response was slightly increased by LPS. Stimulation, most
      prominently with poly(I:C), down-regulated myosin light chain kinase and
      cysteinyl leukotriene 1 receptor expression and up-regulated beta2-adrenoceptor
      expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or
      RIG-I/MDA-5. CONCLUSION: Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a
      synthetic phenotype, characterized by an increased ability to release
      inflammatory mediators, acquire immunomodulatory properties by recruiting and
      interacting with other cells, and reduce the contractile state. The PRRs might
      therefore be of therapeutic use in the management of asthma and infection-induced
      disease exacerbations.

PMID- 23861936
TI  - Seasonal and temporal variation in release of antibiotics in hospital wastewater:
      estimation using continuous and grab sampling.
AB  - The presence of antibiotics in the environment and their subsequent impact on
      resistance development has raised concerns globally. Hospitals are a major source
      of antibiotics released into the environment. To reduce these residues, research
      to improve knowledge of the dynamics of antibiotic release from hospitals is
      essential. Therefore, we undertook a study to estimate seasonal and temporal
      variation in antibiotic release from two hospitals in India over a period of two
      years. For this, 6 sampling sessions of 24 hours each were conducted in the three
      prominent seasons of India, at all wastewater outlets of the two hospitals, using
      continuous and grab sampling methods. An in-house wastewater sampler was designed
      for continuous sampling. Eight antibiotics from four major antibiotic groups were
      selected for the study. To understand the temporal pattern of antibiotic release,
      each of the 24-hour sessions were divided in three sub-sampling sessions of 8
      hours each. Solid phase extraction followed by liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) was used to determine the antibiotic residues. Six of the
      eight antibiotics studied were detected in the wastewater samples. Both
      continuous and grab sampling methods indicated that the highest quantities of
      fluoroquinolones were released in winter followed by the rainy season and the
      summer. No temporal pattern in antibiotic release was detected. In general, in a
      common timeframe, continuous sampling showed less concentration of antibiotics in
      wastewater as compared to grab sampling. It is suggested that continuous sampling
      should be the method of choice as grab sampling gives erroneous results, it being
      indicative of the quantities of antibiotics present in wastewater only at the
      time of sampling. Based on our studies, calculations indicate that from hospitals
      in India, an estimated 89, 1 and 25 ng/L/day of fluroquinolones, metronidazole
      and sulfamethoxazole respectively, might be getting released into the environment
      per 100 hospital beds. 

PMID- 23861937
TI  - Genome-wide screening for genes associated with valproic acid sensitivity in
      fission yeast.
AB  - We have been studying the action mechanisms of valproic acid (VPA) in fission
      yeast Schizosaccharomyces pombe by developing a genetic screen for mutants that
      show hypersensitivity to VPA. In the present study, we performed a genome-wide
      screen of 3004 haploid deletion strains and confirmed 148 deletion strains to be
      VPA sensitive. Of the 148 strains, 93 strains also showed sensitivity to another
      aliphatic acids HDAC inhibitor, sodium butyrate (SB), and 55 strains showed
      sensitivity to VPA but not to SB. Interestingly, we found that both VPA and SB
      treatment induced a marked increase in the transcription activity of Atf1 in wild
      type cells. However, in clr6-1, a mutant allele the clr6(+) gene encoding class I
      HDAC, neither VPA- nor SB induced the activation of Atf1 transcription activity.
      We also found that VPA, but not SB, caused an increase in cytoplasmic Ca(2+)
      level. We further found that the cytoplasmic Ca(2+) increase was caused by Ca(2+)
      influx from extracellular medium via Cch1-Yam8 channel complex. Altogether, our
      present study indicates that VPA and SB play similar but distinct roles in
      multiple physiological processes in fission yeast. 

PMID- 23861938
TI  - Relationship between the autoantibody and expression of beta3-adrenoceptor in
      lung and heart.
AB  - BACKGROUND: Evidences suggest that beta3 -adrenoceptor (beta3-AR) plays an
      important role in heart failure (HF), although no data is reported indicating how
      these effects may change with the increasing age. Pulmonary congestion and edema
      are the major life-threatening complications associated with HF. The purpose of
      this study is to explore the relationship between the anti-beta3-AR autoantibody
      and the expression of beta3-AR in the lungs and heart for both aged patients and
      rats with HF. METHODS: Synthetic beta3-AR peptides served as the target antigens
      in ELISA were used to screen the anti-beta3-AR autoantibody in aged patients and
      rats. Two aged rat models were constructed based on aortic banding and sham
      operation. The expression of beta3-AR mRNA and protein in the lung and heart was
      measured in intervention and non-intervention groups by Western blot analysis at
      the baseline, 5(th), 7(th), 9(th) and 11(th) week, respectively. RESULTS: The
      frequency and titer of anti-beta3-AR autoantibody in aged patients and rats with
      HF were higher than those in the control group (p<0.05). The expression of beta3
      AR mRNA and protein in pulmonary tissues decreased continually from the 7(th)
      week (p<0.05), followed by HF observed during the 9(th) week. The expression of
      beta3-AR in myocardial tissues continued to increase after the 9(th) week
      (p<0.05), and the expression of both beta3-AR mRNA and protein in the BRL group
      [HF group with BRL37344 (4-[-[2-hydroxy-(3-chlorophenyl)ethyl-amino]
      phenoxyacetic acid) (a beta3-AR agonist) injection] was positively correlated
      with BRL37344 when compared with non-BRL group (HF group without BRL37344
      injection) (p<0.05). CONCLUSION: Anti-beta3-AR autoantibody was detected in aged
      patients and rats with HF. The expression of beta3-AR mRNA and protein in
      pulmonary tissues decreased continually, and began earlier than in the heart, but
      its expression in myocardial tissues increased continually and could be further
      promoted by beta3-AR agonist.

PMID- 23861939
TI  - Study on the growth and the photosynthetic characteristics of low energy C(+) ion
      implantation on peanut.
AB  - Employing the Nonghua 5 peanut as experimental material, the effects of low
      energy C(+) ion implantation on caulis height, root length, dry weight,
      photosynthetic characteristics and leaf water use efficiency (WUE) of Peanut Ml
      Generation were studied. Four fluences were observed in the experiment. The
      results showed that ion implantation harmed the peanut seeds because caulis
      height, root length and dry weight all were lower in the treatments than in CK,
      and the harm was aggravated with the increase of ion fluence. Both Pn and Tr show
      a saddle-shape curve due to midday depression of photosynthesis. Low fluence of
      low energy C(+) ion implantation could increase the diurnal average Pn of peanut.
      The diurnal variation of Tr did not change as significantly as Pn. The light
      saturation point (LSP) was restrained by the ions. After low energy C(+) ion
      implantation, WUE was enhanced. When the fluence increased to a certain level,
      the WUE began to decrease. 

PMID- 23861940
TI  - Basic fibroblast growth factor contributes to a shift in the angioregulatory
      activity of retinal glial (Muller) cells.
AB  - Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine with pro
      angiogenic and neurotrophic effects. The angioregulatory role of this molecule
      may become especially significant in retinal neovascularization, which is a
      hallmark of a number of ischemic eye diseases. This study was undertaken to
      reveal expression characteristics of bFGF, produced by retinal glial (Muller)
      cells, and to determine conditions under which glial bFGF may stimulate the
      proliferation of retinal microvascular endothelial cells. Immunofluorescence
      labeling detected bFGF in Muller cells of the rat retina and in acutely isolated
      Muller cells with bFGF levels, which increased after ischemia-reperfusion in
      postischemic retinas. In patients with proliferative diabetic retinopathy or
      myopia, the immunoreactivity of bFGF co-localized to glial fibrillary acidic
      protein (GFAP)-positive cells in surgically excised retinal tissues. RT-PCR and
      ELISA analyses indicated that cultured Muller cells produce bFGF, which is
      elevated under hypoxia or oxidative stress, as well as under stimulation with
      various growth factors and cytokines, including pro-inflammatory factors. When
      retinal endothelial cells were cultured in the presence of media from hypoxia
      (0.2%)-conditioned Muller cells, a distinct picture of endothelial cell
      proliferation emerged. Media from 24-h cultured Muller cells inhibited
      proliferation, whereas 72-h conditioned media elicited a stimulatory effect. BFGF
      neutralizing antibodies suppressed the enhanced endothelial cell proliferation to
      a similar extent as anti-VEGF antibodies. Furthermore, phosphorylation of
      extracellular signal-regulated kinases (ERK-1/-2) in retinal endothelial cells
      was increased when the cells were cultured in 72-h conditioned media, while
      neutralizing bFGF attenuated the activation of this signaling pathway. These data
      provide evidence that retinal (glial) Muller cells are major sources of bFGF in
      the ischemic retina. Muller cells under physiological conditions or transient
      hypoxia seem to provide an anti-angiogenic environment, but long-lasting hypoxia
      causes the release of bFGF, which might significantly co-stimulate
      neovascularization in the retina. 

PMID- 23861941
TI  - A huntingtin peptide inhibits polyQ-huntingtin associated defects.
AB  - BACKGROUND: Huntington's disease (HD) is caused by the abnormal expansion of the
      polyglutamine tract in the human Huntingtin protein (polyQ-hHtt). Although this
      mutation behaves dominantly, huntingtin loss of function also contributes to HD
      pathogenesis. Indeed, wild-type Huntingtin plays a protective role with respect
      to polyQ-hHtt induced defects. METHODOLOGY/PRINCIPAL FINDINGS: The question that
      we addressed here is what part of the wild-type Huntingtin is responsible for
      these protective properties. We first screened peptides from the Huntingtin
      protein in HeLa cells and identified a 23 aa peptide (P42) that inhibits polyQ
      hHtt aggregation. P42 is part of the endogenous Huntingtin protein and lies
      within a region rich in proteolytic sites that plays a critical role in the
      pathogenesis process. Using a Drosophila model of HD, we tested the protective
      properties of this peptide on aggregation, as well as on different polyQ-hHtt
      induced neuronal phenotypes: eye degeneration (an indicator of cell death),
      impairment of vesicular axonal trafficking, and physiological behaviors such as
      larval locomotion and adult survival. Together, our results demonstrate high
      protective properties for P42 in vivo, in whole animals. These data also
      demonstrate a specific role of P42 on Huntington's disease model, since it has no
      effect on other models of polyQ-induced diseases, such as spinocerebellar
      ataxias. CONCLUSIONS/SIGNIFICANCE: Altogether our data show that P42, a 23 aa
      long hHtt peptide, plays a protective role with respect to polyQ-hHtt aggregation
      as well as cellular and behavioral dysfunctions induced by polyQ-hHtt in vivo.
      Our study also confirms the correlation between polyQ-hHtt aggregation and
      neuronal defects. Finally, these results strongly suggest a therapeutic potential
      for P42, specific of Huntington's disease.

PMID- 23861942
TI  - Temperature increase exacerbates apoptotic neuronal death in chemically-induced
      ischemia.
AB  - It is well-established that hyperthermia increases neuronal death and worsens
      stroke outcome. However, little is known about the mechanisms of how hyperthermia
      is involved in this neuronal death process. In the present study, we examined how
      temperature increase exacerbates neuronal death using a model of chemical
      ischemia. Chemical ischemia was induced by treating SH-SY5Y neuroblastoma cells
      with sodium azide and deoxyglucose. Temperature increase was treated by placing
      the cells at 37 degrees C (control) and 41 degrees C (experimental). Cell
      survival was determined by trypan blue assay and ATP levels were measured with
      ATP assay kits. Protein expression was detected by western blot. Treatment with
      sodium azide resulted in cell death in a dose-responsive manner. Increased
      temperature worsened the ATP depletion and cell volume shrinkage. Temperature
      increase also enhanced ER stress as demonstrated by the elevated level of phospho
      eIF2alpha and C/EBP homologous protein (CHOP). Inhibition of CHOP expression
      significantly decreased sodium azide-induced neuronal death. In addition, the
      increased temperature intensified the activation of caspase-3, an apoptotic
      effector protease, and inhibition of capspase-3 significantly reduced cell death.
      These findings support that temperature increase worsened the neuronal death by
      depleting intracellular ATP, inducing ER stress response and activating apoptotic
      signal transduction. 

PMID- 23861943
TI  - CK1delta kinase activity is modulated by Chk1-mediated phosphorylation.
AB  - CK1delta, a member of the casein kinase 1 family, is involved in the regulation
      of various cellular processes and has been associated with the pathophysiology of
      neurodegenerative diseases and cancer. Therefore recently, interest in generating
      highly specific inhibitors for personalized therapy has increased enormously.
      However, the efficacy of newly developed inhibitors is affected by the
      phosphorylation state of CK1delta. Cellular kinases phosphorylating CK1delta
      within its C-terminal domain have been identified but still more information
      regarding the role of site-specific phosphorylation in modulating the activity of
      CK1delta is required. Here we show that Chk1 phosphorylates rat CK1delta at
      serine residues 328, 331, 370, and threonine residue 397 as well as the human
      CK1delta transcription variants 1 and 2. CK1delta mutant proteins bearing one,
      two or three mutations at these identified phosphorylation sites exhibited
      significant differences in their kinetic properties compared to wild-type
      CK1delta. Additionally, CK1delta co-precipitates with Chk1 from HT1080 cell
      extracts and activation of cellular Chk1 resulted in a significant decrease in
      cellular CK1delta kinase activity. Taken together, these data point towards a
      possible regulatory relationship between Chk1 and CK1delta. 

PMID- 23861945
TI  - Lack of visual orienting to biological motion and audiovisual synchrony in 3-year
      olds with autism.
AB  - It has been suggested that children with autism orient towards audiovisual
      synchrony (AVS) rather than biological motion and that the opposite pattern is to
      be expected in typical development. Here, we challenge this notion by showing
      that 3-year-old neurotypical children orient to AVS and to biological motion in
      point-light displays but that 3-year-old children with autism orient to neither
      of these types of information. Thus, our data suggest that two fundamental
      mechanisms are disrupted in young children with autism: one that supports
      orienting towards others' movements and one that supports orienting towards
      multimodally specified events. These impairments may have consequences for socio
      cognitive development and brain organization. 

PMID- 23861944
TI  - An innovative cloning platform enables large-scale production and maturation of
      an oxygen-tolerant [NiFe]-hydrogenase from Cupriavidus necator in Escherichia
      coli.
AB  - Expression of multiple heterologous genes in a dedicated host is a prerequisite
      for approaches in synthetic biology, spanning from the production of recombinant
      multiprotein complexes to the transfer of tailor-made metabolic pathways. Such
      attempts are often exacerbated, due in most cases to a lack of proper
      directional, robust and readily accessible genetic tools. Here, we introduce an
      innovative system for cloning and expression of multiple genes in Escherichia
      coli BL21 (DE3). Using the novel methodology, genes are equipped with individual
      promoters and terminators and subsequently assembled. The resulting multiple gene
      cassettes may either be placed in one vector or alternatively distributed among a
      set of compatible plasmids. We demonstrate the effectiveness of the developed
      tool by production and maturation of the NAD(+)reducing soluble [NiFe]
      hydrogenase (SH) from Cupriavidus necator H16 (formerly Ralstonia eutropha H16)
      in E. coli BL21StarTM (DE3). The SH (encoded in hoxFUYHI) was successfully
      matured by co-expression of a dedicated set of auxiliary genes, comprising seven
      hyp genes (hypC1D1E1A2B2F2X) along with hoxW, which encodes a specific
      endopeptidase. Deletion of genes involved in SH maturation reduced maturation
      efficiency substantially. Further addition of hoxN1, encoding a high-affinity
      nickel permease from C. necator, considerably increased maturation efficiency in
      E. coli. Carefully balanced growth conditions enabled hydrogenase production at
      high cell-densities, scoring mg.(Liter culture)(-1) yields of purified functional
      SH. Specific activities of up to 7.2+/-1.15 U.mg(-1) were obtained in cell-free
      extracts, which is in the range of the highest activities ever determined in C.
      necator extracts. The recombinant enzyme was isolated in equal purity and
      stability as previously achieved with the native form, yielding ultrapure
      preparations with anaerobic specific activities of up to 230 U.mg(-1). Owing to
      the combinatorial power exhibited by the presented cloning platform, the system
      might represent an important step towards new routes in synthetic biology. 

PMID- 23861946
TI  - Iron status and Helicobacter pylori infection in symptomatic children: an
      international multi-centered study.
AB  - OBJECTIVE: Iron deficiency (ID) and iron deficiency anaemia (IDA) are global
      major public health problems, particularly in developing countries. Whilst an
      association between H. pylori infection and ID/IDA has been proposed in the
      literature, currently there is no consensus. We studied the effects of H. pylori
      infection on ID/IDA in a cohort of children undergoing upper gastrointestinal
      endoscopy for upper abdominal pain in two developing and one developed country.
      METHODS: In total 311 children (mean age 10.7+/-3.2 years) from Latin America-
      Belo Horizonte/Brazil (n = 125), Santiago/Chile (n = 105)--and London/UK (n =
      81), were studied. Gastric and duodenal biopsies were obtained for evaluation of
      histology and H. pylori status and blood samples for parameters of ID/IDA.
      RESULTS: The prevalence of H. pylori infection was 27.7% being significantly
      higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear
      regression models revealed H. pylori infection as a significant predictor of low
      ferritin and haemoglobin concentrations in children from Latin-America. A
      negative correlation was observed between MCV (r = -0.26; p = 0.01) and MCH (r = 
      0.27; p = 0.01) values and the degree of antral chronic inflammation, and between
      MCH and the degree of corpus chronic (r = -0.29, p = 0.008) and active (r = 
      0.27, p = 0.002) inflammation. CONCLUSIONS: This study demonstrates that H.
      pylori infection in children influences the serum ferritin and haemoglobin
      concentrations, markers of early depletion of iron stores and anaemia
      respectively.

PMID- 23861947
TI  - Fast detection of nutrient limitation in macroalgae and seagrass with nutrient
      induced fluorescence.
AB  - BACKGROUND: Rapid determination of which nutrients limit the primary production
      of macroalgae and seagrasses is vital for understanding the impacts of
      eutrophication on marine and freshwater ecosystems. However, current methods to
      assess nutrient limitation are often cumbersome and time consuming. For
      phytoplankton, a rapid method has been described based on short-term changes in
      chlorophyll fluorescence upon nutrient addition, also known as Nutrient-Induced
      Fluorescence Transients (NIFTs). Thus far, though, the NIFT technique was not
      well suited for macroalgae and seagrasses. METHODOLOGY & PRINCIPAL FINDINGS: We
      developed a new experimental setup so that the NIFT technique can be used to
      assess nutrient limitation of benthic macroalgae and seagrasses. We first tested
      the applicability of the technique on sea lettuce (Ulva lactuca) cultured in the
      laboratory on nutrient-enriched medium without either nitrogen or phosphorus.
      Addition of the limiting nutrient resulted in a characteristic change in the
      fluorescence signal, whereas addition of non-limiting nutrients did not yield a
      response. Next, we applied the NIFT technique to field samples of the encrusting
      fan-leaf alga Lobophora variegata, one of the key algal species often involved in
      the degradation of coral reef ecosystems. The results pointed at co-limitation of
      L. variegata by phosphorus and nitrogen, although it responded more strongly to
      phosphate than to nitrate and ammonium addition. For turtle grass (Thalassia
      testudinum) we found the opposite result, with a stronger NIFT response to
      nitrate and ammonium than to phosphate. CONCLUSIONS & SIGNIFICANCE: Our extension
      of the NIFT technique offers an easy and fast method (30-60 min per sample) to
      determine nutrient limitation of macroalgae and seagrasses. We successfully
      applied this technique to macroalgae on coral reef ecosystems and to seagrass in
      a tropical inner bay, and foresee wider application to other aquatic plants, and
      to other marine and freshwater ecosystems.

PMID- 23861948
TI  - LHX3 interacts with inhibitor of histone acetyltransferase complex subunits LANP
      and TAF-1beta to modulate pituitary gene regulation.
AB  - LIM-homeodomain 3 (LHX3) is a transcription factor required for mammalian
      pituitary gland and nervous system development. Human patients and animal models
      with LHX3 gene mutations present with severe pediatric syndromes that feature
      hormone deficiencies and symptoms associated with nervous system dysfunction. The
      carboxyl terminus of the LHX3 protein is required for pituitary gene regulation,
      but the mechanism by which this domain operates is unknown. In order to better
      understand LHX3-dependent pituitary hormone gene transcription, we used
      biochemical and mass spectrometry approaches to identify and characterize
      proteins that interact with the LHX3 carboxyl terminus. This approach identified
      the LANP/pp32 and TAF-1beta/SET proteins, which are components of the inhibitor
      of histone acetyltransferase (INHAT) multi-subunit complex that serves as a
      multifunctional repressor to inhibit histone acetylation and modulate chromatin
      structure. The protein domains of LANP and TAF-1beta that interact with LHX3 were
      mapped using biochemical techniques. Chromatin immunoprecipitation experiments
      demonstrated that LANP and TAF-1beta are associated with LHX3 target genes in
      pituitary cells, and experimental alterations of LANP and TAF-1beta levels
      affected LHX3-mediated pituitary gene regulation. Together, these data suggest
      that transcriptional regulation of pituitary genes by LHX3 involves regulated
      interactions with the INHAT complex. 

PMID- 23861949
TI  - Celastrol inhibits lipopolysaccharide-stimulated rheumatoid fibroblast-like
      synoviocyte invasion through suppression of TLR4/NF-kappaB-mediated matrix
      metalloproteinase-9 expression.
AB  - Invasion of fibroblast-like synoviocytes (FLSs) is critical in the pathogenesis
      of rheumatoid arthritis (RA). The metalloproteinases (MMPs) and activator of Toll
      like receptor 4 (TLR4)/nuclear factor-kappaB (NF-kappaB) pathway play a critical
      role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study
      aimed to explore the anti-invasive activity of celastrol on LPS-stimulated human
      RA-FLSs, and to elucidate the mechanism involved. We investigated the effect of
      celastrol on LPS-induced FLS migration and invasion as well as MMP expression and
      explored the upstream signal transduction. Results showed that celastrol
      suppressed LPS-stimulated FLS migration and invasion by inhibiting MMP-9
      expression and activity. Furthermore, our results revealed that celastrol
      inhibited the transcriptional activity of MMP-9 by suppressing the binding
      activity of NF-kappaB in the MMP-9 promoter, and suppressed the TLR4/MyD88/NF
      kappaB pathway. Administration of celastrol (0.5 mg/kg and 1 mg/kg,
      intraperitoneally) daily for 3 weeks in a collagen-induced arthritis rat model
      markedly alleviated the clinical signs, synovial hyperplasia and inflammatory
      cell infiltration of joints. In conclusion, celastrol might inhibit FLS migration
      and invasion induced by LPS by suppressing TLR4/NF-kappaB-mediated MMP-9
      expression, providing a theoretical foundation for the clinical treatment of RA
      with celastrol. 

PMID- 23861950
TI  - Renal hyperfiltration and systemic blood pressure in patients with uncomplicated
      type 1 diabetes mellitus.
AB  - BACKGROUND: Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration
      also exhibit systemic microvascular abnormalities, including endothelial
      dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP)
      is less clear. We therefore measured BP, renal hemodynamic function and
      circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM
      patients with hyperfiltration (n = 36, DM-H, GFR>=135 ml/min/1.73 m(2)) or
      normofiltration (n = 40, DM-N), and 56 healthy controls (HC). Since renal
      hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized
      that hyperfiltration would be associated with higher BP and elevated levels of
      circulating RAAS mediators. METHODS: BP, glomerular filtration rate (GFR -
      inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS
      components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6
      mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9
      11 mmol/L). RESULTS: Baseline GFR was elevated in DM-H vs. DM-N and HC (167+/-6
      vs. 115+/-2 and 115+/-2 ml/min/1.73 m(2), p<0.0001). Baseline systolic BP (SBP,
      117+/-2 vs. 111+/-2 vs. 109+/-1, p = 0.004) and heart rate (76+/-1 vs. 67+/-1 vs.
      61+/-1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM
      H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42+/-5 vs. 86+/-14 vs.
      276+/-41 ng/dl, p = 0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during
      hyperglycemia in DM-N but not in DM-H. CONCLUSIONS: DM-H was associated with
      higher heart rate and SBP values and an exaggerated suppression of systemic
      aldosterone. Future work should focus on the mechanisms that explain this paradox
      in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.

PMID- 23861951
TI  - BrainNet Viewer: a network visualization tool for human brain connectomics.
AB  - The human brain is a complex system whose topological organization can be
      represented using connectomics. Recent studies have shown that human connectomes
      can be constructed using various neuroimaging technologies and further
      characterized using sophisticated analytic strategies, such as graph theory.
      These methods reveal the intriguing topological architectures of human brain
      networks in healthy populations and explore the changes throughout normal
      development and aging and under various pathological conditions. However, given
      the huge complexity of this methodology, toolboxes for graph-based network
      visualization are still lacking. Here, using MATLAB with a graphical user
      interface (GUI), we developed a graph-theoretical network visualization toolbox,
      called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models.
      Within this toolbox, several combinations of defined files with connectome
      information can be loaded to display different combinations of brain surface,
      nodes and edges. In addition, display properties, such as the color and size of
      network elements or the layout of the figure, can be adjusted within a
      comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the
      brain surface, nodes and edges in sequence and displays brain networks in
      multiple views, as required by the user. The figure can be manipulated with
      certain interaction functions to display more detailed information. Furthermore,
      the figures can be exported as commonly used image file formats or demonstration
      video for further use. BrainNet Viewer helps researchers to visualize brain
      networks in an easy, flexible and quick manner, and this software is freely
      available on the NITRC website (www.nitrc.org/projects/bnv/). 

PMID- 23861952
TI  - Development of a gravid trap for collecting live malaria vectors Anopheles
      gambiae s.l.
AB  - BACKGROUND: Effective malaria vector control targeting indoor host-seeking
      mosquitoes has resulted in fewer vectors entering houses in many areas of sub
      Saharan Africa, with the proportion of vectors outdoors becoming more important
      in the transmission of this disease. This study aimed to develop a gravid trap
      for the outdoor collection of the malaria vector Anopheles gambiae s.l. based on
      evaluation and modification of commercially available gravid traps. METHODS:
      Experiments were implemented in an 80 m(2) semi-field system where 200 gravid
      Anopheles gambiae s.s. were released nightly. The efficacy of the Box, CDC and
      Frommer updraft gravid traps was compared. The Box gravid trap was tested to
      determine if the presence of the trap over water and the trap's sound affected
      catch size. Mosquitoes approaching the treatment were evaluated using
      electrocuting nets or detergents added to the water in the trap. Based on the
      results, a new gravid trap (OviART trap) that provided an open, unobstructed
      oviposition site was developed and evaluated. RESULTS: Box and CDC gravid traps
      collected similar numbers (relative rate (RR) 0.8, 95% confidence interval (CI)
      0.6-1.2; p = 0.284), whereas the Frommer trap caught 70% fewer mosquitoes (RR
      0.3, 95% CI 0.2-0.5; p < 0.001). The number of mosquitoes approaching the Box
      trap was significantly reduced when the trap was positioned over a water-filled
      basin compared to an open pond (RR 0.7 95% CI 0.6-0.7; p < 0.001). This effect
      was not due to the sound of the trap. Catch size increased by 60% (RR 1.6, 1.2
      2.2; p = 0.001) with the new OviART trap. CONCLUSION: Gravid An. Gambiae s.s.
      females were visually deterred by the presence of the trapping device directly
      over the oviposition medium. Based on these investigations, an effective gravid
      trap was developed that provides open landing space for egg-laying Anopheles.

PMID- 23861953
TI  - Probiotics can generate FoxP3 T-cell responses in the small intestine and
      simultaneously inducing CD4 and CD8 T cell activation in the large intestine.
AB  - Most studies on probiotics aim to restore intestinal homeostasis to reduce immune
      pathology in disease. Of equal importance are studies on how probiotics might
      prevent or delay disease in healthy individuals. However, knowledge on mechanisms
      of probiotic actions in healthy individuals is scarce. To gain more insight in
      how different bacterial strains may modulate the healthy intestinal immune
      system, we investigated the effect of the food derived bacterial strains L.
      plantarum WCFS1, L. salivarius UCC118, and L. lactis MG1363, on the intestinal
      regulatory immune phenotype in healthy mice. All three bacterial strains induced
      an upregulation of activity and numbers of CD11c(+) MHCII(+) DCs in the immune
      sampling Peyer's Patches. Only L. salivarius UCC118 skewed towards an immune
      regulatory phenotype in the small intestinal lamina propria (SILP). The effects
      were different in the large intestine lamina propria. L. salivarius UCC118
      induced activation in both CD4 and CD8 positive T-cells while L. plantarum WCFS1
      induced a more regulatory phenotype. Moreover, L. plantarum WCFS1 decreased the
      Th1/Th2 ratio in the SILP. Also L. lactis MG1363 had immunomodulatory effects. L.
      lactis MG1363 decreased the expression of the GATA-3 and T-bet in the SILP. As
      our data show that contradictory effects may occur in different parts of the gut,
      it is recommended to study effects of probiotic in different sites in the
      intestine. Our strain-specific results suggest that unspecified application of
      probiotics may not be very effective. Our data also indicate that selection of
      specific probiotic strain activities on the basis of responses in healthy mice
      may be a promising strategy to specifically stimulate or suppress immunity in
      specific parts of the intestine. 

PMID- 23861954
TI  - Comparative genome sequence analysis of Choristoneura occidentalis Freeman and C.
      rosaceana Harris (Lepidoptera: Tortricidae) alphabaculoviruses.
AB  - The complete genome sequences of Choristoneura occidentalis and C. rosaceana
      nucleopolyhedroviruses (ChocNPV and ChroNPV, respectively) (Baculoviridae:
      Alphabaculovirus) were determined and compared with each other and with those of
      other baculoviruses, including the genome of the closely related C. fumiferana
      NPV (CfMNPV). The ChocNPV genome was 128,446 bp in length (1147 bp smaller than
      that of CfMNPV), had a G+C content of 50.1%, and contained 148 open reading
      frames (ORFs). In comparison, the ChroNPV genome was 129,052 bp in length, had a
      G+C content of 48.6% and contained 149 ORFs. ChocNPV and ChroNPV shared 144 ORFs
      in common, and had a 77% sequence identity with each other and 96.5% and 77.8%
      sequence identity, respectively, with CfMNPV. Five homologous regions (hrs), with
      sequence similarities to those of CfMNPV, were identified in ChocNPV, whereas the
      ChroNPV genome contained three hrs featuring up to 14 repeats. Both genomes
      encoded three inhibitors of apoptosis (IAP-1, IAP-2, and IAP-3), as reported for
      CfMNPV, and the ChocNPV IAP-3 gene represented the most divergent functional
      region of this genome relative to CfMNPV. Two ORFs were unique to ChocNPV, and
      four were unique to ChroNPV. ChroNPV ORF chronpv38 is a eukaryotic initiation
      factor 5 (eIF-5) homolog that has also been identified in the C. occidentalis
      granulovirus (ChocGV) and is believed to be the product of horizontal gene
      transfer from the host. Based on levels of sequence identity and phylogenetic
      analysis, both ChocNPV and ChroNPV fall within group I alphabaculoviruses, where
      ChocNPV appears to be more closely related to CfMNPV than does ChroNPV. Our
      analyses suggest that it may be appropriate to consider ChocNPV and CfMNPV as
      variants of the same virus species. 

PMID- 23861955
TI  - A novel 3D label-free monitoring system of hES-derived cardiomyocyte clusters: a
      step forward to in vitro cardiotoxicity testing.
AB  - Unexpected adverse effects on the cardiovascular system remain a major challenge
      in the development of novel active pharmaceutical ingredients (API). To overcome
      the current limitations of animal-based in vitro and in vivo test systems, stem
      cell derived human cardiomyocyte clusters (hCMC) offer the opportunity for highly
      predictable pre-clinical testing. The three-dimensional structure of hCMC appears
      more representative of tissue milieu than traditional monolayer cell culture.
      However, there is a lack of long-term, real time monitoring systems for tissue
      like cardiac material. To address this issue, we have developed a microcavity
      array (MCA)-based label-free monitoring system that eliminates the need for
      critical hCMC adhesion and outgrowth steps. In contrast, feasible field potential
      derived action potential recording is possible immediately after positioning
      within the microcavity. Moreover, this approach allows extended observation of
      adverse effects on hCMC. For the first time, we describe herein the monitoring of
      hCMC over 35 days while preserving the hCMC structure and electrophysiological
      characteristics. Furthermore, we demonstrated the sensitive detection and
      quantification of adverse API effects using E4031, doxorubicin, and noradrenaline
      directly on unaltered 3D cultures. The MCA system provides multi-parameter
      analysis capabilities incorporating field potential recording, impedance
      spectroscopy, and optical read-outs on individual clusters giving a comprehensive
      insight into induced cellular alterations within a complex cardiac culture over
      days or even weeks. 

PMID- 23861956
TI  - Early life stress and physical and psychosocial functioning in late adulthood.
AB  - BACKGROUND: Severe stress experienced in early life may have long-term effects on
      adult physiological and psychological health and well-being. We studied physical
      and psychosocial functioning in late adulthood in subjects separated temporarily
      from their parents in childhood during World War II. METHODS: The 1803
      participants belong to the Helsinki Birth Cohort Study, born 1934-44. Of them,
      267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining
      subjects served as controls. Physical and psychosocial functioning was assessed
      with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was
      based on linear regression. All analyses were adjusted for age at clinical
      examination, social class in childhood and adulthood, smoking, alcohol intake,
      physical activity, body mass index, cardiovascular disease and diabetes. RESULTS:
      Physical functioning in late adulthood was lower among the separated men compared
      to non-separated men (b = -0.40, 95% confidence interval [95% CI]: -0.71 to 
      0.08). Those men separated in school age (>7 years) and who were separated for a
      duration over 2 years had the highest risk for lower physical functioning (b = 
      0.89, 95% CI: -1.58 to -0.20) and (b = -0.65, 95% CI: -1.25 to -0.05),
      respectively). Men separated for a duration over 2 years also had lower
      psychosocial functioning (b = -0.70, 95% CI: -1.35 to -0.06). These differences
      in physical and psychosocial functioning were not observed among women.
      CONCLUSION: Early life stress may increase the risk for impaired physical
      functioning in late adulthood among men. Timing and duration of the separation
      influenced the physical and psychosocial functioning in late adulthood.

PMID- 23861957
TI  - Erosive arthritis and hepatic granuloma formation induced by peptidoglycan
      polysaccharide in rats is aggravated by prasugrel treatment.
AB  - Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel,
      increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS)
      in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if
      the detrimental effects are caused exclusively by clopidogrel, we evaluated
      prasugrel, a third-generation thienopyridine pro-drug, that contrary to
      clopidogrel is mostly metabolized into its active metabolite in the intestine.
      Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive
      arthritis was induced in Lewis rats followed by treatment with prasugrel for 21
      days. Prasugrel treated arthritic animals showed a significant increase in the
      inflammatory response, compared with untreated arthritic rats, in terms of
      augmented macroscopic joint diameter associated with significant signs of
      inflammation, histomorphometric measurements of the hind joints and elevated
      platelet number. Moreover, fibrosis at the pannus, assessed by immunofluorescence
      of connective tissue growth factor, was increased in arthritic rats treated with
      prasugrel. In addition to the arthritic manifestations, hepatomegaly, liver
      granulomas and giant cell formation were observed after PG-PS induction and even
      more after prasugrel exposure. Cytokine plasma levels of IL-1 beta, IL-6, MIP1
      alpha, MCP1, IL-17 and RANTES were increased in arthritis-induced animals. IL-10
      plasma levels were significantly decreased in animals treated with prasugrel.
      Overall, prasugrel enhances inflammation in joints and liver of this animal
      model. Since prasugrel metabolites inhibit neutrophil function ex-vivo and the
      effects of both clopidogrel and prasugrel metabolites on platelets are identical,
      we conclude that the thienopyridines metabolites might exert non-platelet effects
      on other immune cells to aggravate inflammation. 

PMID- 23861958
TI  - Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase
      2: inhibiting the receptor that is overactive in fibrodysplasia ossificans
      progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare heritable disease
      characterized by progressive heterotopic ossification of connective tissues, for
      which there is presently no definite treatment. A recurrent activating mutation
      (c.617G->A; R206H) of activin receptor-like kinase 2 (ACVR1/ALK2), a BMP type I
      receptor, has been shown as the main cause of FOP. This mutation constitutively
      activates the BMP signaling pathway and initiates the formation of heterotopic
      bone. In this study, we have designed antisense oligonucleotides (AONs) to
      knockdown mouse ALK2 expression by means of exon skipping. The ALK2 AON could
      induce exon skipping in cells, which was accompanied by decreased ALK2 mRNA
      levels and impaired BMP signaling. In addition, the ALK2 AON potentiated muscle
      differentiation and repressed BMP6-induced osteoblast differentiation. Our
      results therefore provide a potential therapeutic approach for the treatment of
      FOP disease by reducing the excessive ALK2 activity in FOP patients. 

PMID- 23861959
TI  - SMAP2 regulates retrograde transport from recycling endosomes to the Golgi.
AB  - Retrograde transport is where proteins and lipids are transported back from the
      plasma membrane (PM) and endosomes to the Golgi, and crucial for a diverse range
      of cellular functions. Recycling endosomes (REs) serve as a sorting station for
      the retrograde transport and we recently identified evection-2, an RE protein
      with a pleckstrin homology (PH) domain, as an essential factor of this pathway.
      How evection-2 regulates retrograde transport from REs to the Golgi is not well
      understood. Here, we report that evection-2 binds to SMAP2, an Arf GTPase
      activating protein. Endogenous SMAP2 localized mostly in REs and to a lesser
      extent, the trans-Golgi network (TGN). SMAP2 binds evection-2, and the RE
      localization of SMAP2 was abolished in cells depleted of evection-2. Knockdown of
      SMAP2, like that of evection-2, impaired the retrograde transport of cholera
      toxin B subunit (CTxB) from REs. These findings suggest that evection-2 recruits
      SMAP2 to REs, thereby regulating the retrograde transport of CTxB from REs to the
      Golgi. 

PMID- 23861960
TI  - P53 family members modulate the expression of PRODH, but not PRODH2, via intronic
      p53 response elements.
AB  - The tumor suppressor p53 was previously shown to markedly up-regulate the
      expression of the PRODH gene, encoding the proline dehydrogenase (PRODH) enzyme,
      which catalyzes the first step in proline degradation. Also PRODH2, which
      degrades 4-hydroxy-L-proline, a product of protein (e.g. collagen) catabolism,
      was recently described as a p53 target. Here, we confirmed p53-dependent
      induction of endogenous PRODH in response to genotoxic damage in cell lines of
      different histological origin. We established that over-expression of TAp73beta
      or TAp63beta is sufficient to induce PRODH expression in p53-null cells and that
      PRODH expression parallels the modulation of endogenous p73 by genotoxic drugs in
      several cell lines. The p53, p63, and p73-dependent transcriptional activation
      was linked to specific intronic response elements (REs), among those predicted by
      bioinformatics tools and experimentally validated by a yeast-based
      transactivation assay. p53 occupancy measurements were validated in HCT116 and
      MCF7 human cell lines. Conversely, PRODH2 was not responsive to p63 nor p73 and,
      at best, could be considered a weak p53 target. In fact, minimal levels of PRODH2
      transcript induction by genotoxic stress was observed exclusively in one of four
      p53 wild-type cell lines tested. Consistently, all predicted p53 REs in PRODH2
      were poor matches to the p53 RE consensus and showed very weak responsiveness,
      only to p53, in the functional assay. Taken together, our results highlight that
      PRODH, but not PRODH2, expression is under the control of p53 family members,
      specifically p53 and p73. This supports a deeper link between proteins of the p53
      family and metabolic pathways, as PRODH modulates the balance of proline and
      glutamate levels and those of their derivative alpha-keto-glutarate (alpha-KG)
      under normal and pathological (tumor) conditions. 

PMID- 23861961
TI  - Mitochondrial hyperfusion during oxidative stress is coupled to a dysregulation
      in calcium handling within a C2C12 cell model.
AB  - Atrial Fibrillation is the most common sustained cardiac arrhythmia worldwide
      harming millions of people every year. Atrial Fibrillation (AF) abruptly induces
      rapid conduction between atrial myocytes which is associated with oxidative
      stress and abnormal calcium handling. Unfortunately this new equilibrium promotes
      perpetuation of the arrhythmia. Recently, in addition to being the major source
      of oxidative stress within cells, mitochondria have been observed to fuse,
      forming mitochondrial networks and attach to intracellular calcium stores in
      response to cellular stress. We sought to identify a potential role for rapid
      stimulation, oxidative stress and mitochondrial hyperfusion in acute changes to
      myocyte calcium handling. In addition we hoped to link altered calcium handling
      to increased sarcoplasmic reticulum (SR)-mitochondrial contacts, the so-called
      mitochondrial associated membrane (MAM). We selected the C2C12 murine myotube
      model as it has previously been successfully used to investigate mitochondrial
      dynamics and has a myofibrillar system similar to atrial myocytes. We observed
      that rapid stimulation of C2C12 cells resulted in mitochondrial hyperfusion and
      increased mitochondrial colocalisation with calcium stores. Inhibition of
      mitochondrial fission by transfection of mutant DRP1K38E resulted in similar
      effects on mitochondrial fusion, SR colocalisation and altered calcium handling.
      Interestingly the effects of 'forced fusion' were reversed by co-incubation with
      the reducing agent N-Acetyl cysteine (NAC). Subsequently we demonstrated that
      oxidative stress resulted in similar reversible increases in mitochondrial
      fusion, SR-colocalisation and altered calcium handling. Finally, we believe we
      have identified that myocyte calcium handling is reliant on baseline levels of
      reactive oxygen species as co-incubation with NAC both reversed and retarded
      myocyte response to caffeine induced calcium release and re-uptake. Based on
      these results we conclude that the coordinate regulation of mitochondrial fusion
      and MAM contacts may form a point source for stress-induced arrhythmogenesis. We
      believe that the MAM merits further investigation as a therapeutic target in AF
      induced remodelling. 

PMID- 23861962
TI  - Fate mapping for activation-induced cytidine deaminase (AID) marks non-lymphoid
      cells during mouse development.
AB  - The Aicda gene encodes Activation-Induced cytidine Deaminase (AID), an enzyme
      essential for remodeling antibody genes in mature B lymphocytes. AID is also
      responsible for DNA damage at oncogenes, leading to their mutation and cancer
      associated chromosome translocation in lymphoma. We used fate mapping and
      AID(GFP) reporter mice to determine if AID expression in the mouse extends beyond
      lymphocytes. We discovered that AID(cre) tags a small fraction of non-lymphoid
      cells starting at 10.5 days post conception (dpc), and that AID(GFP+) cells are
      detectable at dpc 11.5 and 12.5. Embryonic cells are tagged by AID(cre) in the
      submandibular region, where conditional deletion of the tumor suppressor PTEN
      causes squamous papillomas. AID(cre) also tags non-lymphoid cells in the
      embryonic central nervous system. Finally, in the adult mouse brain, AID(cre)
      marks a small fraction of diverse neurons and distinct neuronal populations,
      including pyramidal cells in cortical layer IV. 

PMID- 23861963
TI  - The effect of illumination and time of day on movements of bobcats (Lynx rufus).
AB  - Understanding behavioral changes of prey and predators based on lunar
      illumination provides insight into important life history, behavioral ecology,
      and survival information. The objectives of this research were to determine if
      bobcat movement rates differed by period of day (dark, moon, crepuscular, day),
      lunar illumination (<10%, 10 - <50%, 50 - <90%, >90%), and moon phase (new,
      full). Bobcats had high movement rates during crepuscular and day periods and low
      movement rates during dark periods with highest nighttime rates at 10-<50% lunar
      illumination. Bobcats had highest movement rates during daytime when nighttime
      illumination was low (new moon) and higher movement rates during nighttime when
      lunar illumination was high (full moon). The behaviors we observed are consistent
      with prey availability being affected by light level and by limited vision by
      bobcats during darkness. 

PMID- 23861964
TI  - Loss of 'blue carbon' from coastal salt marshes following habitat disturbance.
AB  - Increased recognition of the global importance of salt marshes as 'blue carbon'
      (C) sinks has led to concern that salt marshes could release large amounts of
      stored C into the atmosphere (as CO2) if they continue undergoing disturbance,
      thereby accelerating climate change. Empirical evidence of C release following
      salt marsh habitat loss due to disturbance is rare, yet such information is
      essential for inclusion of salt marshes in greenhouse gas emission reduction and
      offset schemes. Here we investigated the stability of salt marsh
      (Spartinaalterniflora) sediment C levels following seagrass (Thallasiatestudinum)
      wrack accumulation; a form of disturbance common throughout the world that
      removes large areas of plant biomass in salt marshes. At our study site (St
      Joseph Bay, Florida, USA), we recorded 296 patches (7.5 +/- 2.3 m(2) mean area +/
      SE) of vegetation loss (aged 3-12 months) in a salt marsh meadow the size of a
      soccer field (7 275 m(2)). Within these disturbed patches, levels of organic C in
      the subsurface zone (1-5 cm depth) were ~30% lower than the surrounding
      undisturbed meadow. Subsequent analyses showed that the decline in subsurface C
      levels in disturbed patches was due to loss of below-ground plant (salt marsh)
      biomass, which otherwise forms the main component of the long-term 'refractory' C
      stock. We conclude that disturbance to salt marsh habitat due to wrack
      accumulation can cause significant release of below-ground C; which could shift
      salt marshes from C sinks to C sources, depending on the intensity and scale of
      disturbance. This mechanism of C release is likely to increase in the future due
      to sea level rise; which could increase wrack production due to increasing
      storminess, and will facilitate delivery of wrack into salt marsh zones due to
      higher and more frequent inundation. 

PMID- 23861966
TI  - The statistical analysis of multi-voxel patterns in functional imaging.
AB  - The goal of multi-voxel pattern analysis (MVPA) in BOLD imaging is to determine
      whether patterns of activation across multiple voxels change with experimental
      conditions. MVPA is a powerful technique, its use is rapidly growing, but it
      poses serious statistical challenges. For instance, it is well-known that the
      slow nature of the BOLD response can lead to greatly exaggerated performance
      estimates. Methods are available to avoid this overestimation, and we present
      those here in tutorial fashion. We go on to show that, even with these methods,
      standard tests of significance such as Students' T and the binomial tests are
      invalid in typical MRI experiments. Only a carefully constructed permutation test
      correctly assesses statistical significance. Furthermore, our simulations show
      that performance estimates increase with both temporal as well as spatial signal
      correlations among multiple voxels. This dependence implies that a comparison of
      MVPA performance between areas, between subjects, or even between BOLD signals
      that have been preprocessed in different ways needs great care. 

PMID- 23861965
TI  - Infection rate and tissue localization of murine IL-12p40-producing monocyte
      derived CD103(+) lung dendritic cells during pulmonary tuberculosis.
AB  - Non-hematopoietic cells, including lung epithelial cells, influence host immune
      responses. By co-culturing primary alveolar epithelial cells and monocytes from
      naive donor mice, we show that alveolar epithelial cells support monocyte
      survival and differentiation in vitro, suggesting a role for non-hematopoietic
      cells in monocyte differentiation during the steady state in vivo. CD103(+)
      dendritic cells (alphaE-DC) are present at mucosal surfaces. Using a murine
      primary monocyte adoptive transfer model, we demonstrate that alphaE-DC in the
      lungs and pulmonary lymph nodes are monocyte-derived during pulmonary
      tuberculosis. The tissue localization may influence the functional potential of
      alphaE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we
      confirm the localization of alphaE-DC in uninfected mice beneath the bronchial
      epithelial cell layer and near the vascular wall, and show that alphaE-DC have a
      similar distribution in the lungs during pulmonary tuberculosis and are detected
      in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted
      by M. tuberculosis in vivo and play a role in bacterial dissemination to the
      draining lymph node. In contrast to other DC subsets, only a fraction of lung
      alphaE-DC are infected with the bacterium. We also show that virulent M.
      tuberculosis does not significantly alter cell surface expression levels of MHC
      class II on infected cells in vivo and that alphaE-DC contain the highest
      frequency of IL-12p40(+) cells among the myeloid cell subsets in infected lungs.
      Our results support a model in which inflammatory monocytes are recruited into
      the M. tuberculosis-infected lung tissue and, depending on which non
      hematopoietic cells they interact with, differentiate along different paths to
      give rise to multiple monocyte-derived cells, including DC with a distinctive
      alphaE-DC phenotype. 

PMID- 23861968
TI  - Maximal aerobic and anaerobic power generation in large crocodiles versus
      mammals: implications for dinosaur gigantothermy.
AB  - Inertial homeothermy, the maintenance of a relatively constant body temperature
      that occurs simply because of large size, is often applied to large dinosaurs.
      Moreover, biophysical modelling and actual measurements show that large
      crocodiles can behaviourally achieve body temperatures above 30 degrees C.
      Therefore it is possible that some dinosaurs could achieve high and stable body
      temperatures without the high energy cost of typical endotherms. However it is
      not known whether an ectothermic dinosaur could produce the equivalent amount of
      muscular power as an endothermic one. To address this question, this study
      analyses maximal power output from measured aerobic and anaerobic metabolism in
      burst exercising estuarine crocodiles, Crocodylusporosus, weighing up to 200 kg.
      These results are compared with similar data from endothermic mammals. A 1 kg
      crocodile at 30 degrees C produces about 16 watts from aerobic and anaerobic
      energy sources during the first 10% of exhaustive activity, which is 57% of that
      expected for a similarly sized mammal. A 200 kg crocodile produces about 400
      watts, or only 14% of that for a mammal. Phosphocreatine is a minor energy
      source, used only in the first seconds of exercise and of similar concentrations
      in reptiles and mammals. Ectothermic crocodiles lack not only the absolute power
      for exercise, but also the endurance, that are evident in endothermic mammals.
      Despite the ability to achieve high and fairly constant body temperatures,
      therefore, large, ectothermic, crocodile-like dinosaurs would have been
      competitively inferior to endothermic, mammal-like dinosaurs with high aerobic
      power. Endothermy in dinosaurs is likely to explain their dominance over mammals
      in terrestrial ecosystems throughout the Mesozoic. 

PMID- 23861967
TI  - Human Ubc9 is involved in intracellular HIV-1 Env stability after trafficking out
      of the trans-Golgi network in a Gag dependent manner.
AB  - The cellular E2 Sumo conjugase, Ubc9 interacts with HIV-1 Gag, and is important
      for the assembly of infectious HIV-1 virions. In the previous study we
      demonstrated that in the absence of Ubc9, a defect in virion assembly was
      associated with decreased levels of mature intracellular Envelope (Env) that
      affected Env incorporation into virions and virion infectivity. We have further
      characterized the effect of Ubc9 knockdown on HIV Env processing and assembly. We
      found that gp160 stability in the endoplasmic reticulum (ER) and its trafficking
      to the trans-Golgi network (TGN) were unaffected, indicating that the decreased
      intracellular mature Env levels in Ubc9-depleted cells were due to a selective
      degradation of mature Env gp120 after cleavage from gp160 and trafficked out of
      the TGN. Decreased levels of Gag and mature Env were found to be associated with
      the plasma membrane and lipid rafts, which suggest that these viral proteins were
      not trafficked correctly to the assembly site. Intracellular gp120 were partially
      rescued when treated with a combination of lysosome inhibitors. Taken together
      our results suggest that in the absence of Ubc9, gp120 is preferentially degraded
      in the lysosomes likely before trafficking to assembly sites leading to the
      production of defective virions. This study provides further insight in the
      processing and packaging of the HIV-1 gp120 into mature HIV-1 virions. 

PMID- 23861969
TI  - Concurrent infection of hepatitis B virus negatively affects the clinical outcome
      and prognosis of patients with non-Hodgkin's lymphoma after chemotherapy.
AB  - Hepatitis B virus (HBV) is hepatotropic and lymphotropic. HBV-infected
      individuals have an increased risk of developing malignant lymphoma, and the HBV
      infection rate in lymphoma patients is significantly higher than that in the
      general population. However, the exact mechanism and correlation between HBV
      infection and lymphoma onset and progression currently remain unclear. We
      retrospectively analyzed clinical data from non-Hodgkin's lymphoma (NHL) patients
      with different HBV infection statuses. The results showed that the HBV infection
      rate was significantly higher in patients with B-cell type and late stage of NHL.
      The chemotherapy efficacy for NHL patients with chronic active HBV infection was
      significantly lower than that for the patients with chronic inactive HBV
      infection, the patients with HBV carriers and the patients without HBV infection.
      In addition, the NHL chemotherapy activated HBV replication and caused
      significant liver dysfunction, which could further reduce the chemotherapy
      efficacy. Through Kaplan-Meier survival curve and log-rank analysis, we found
      that the HBV infection status in NHL patients was significantly correlated with
      the patients' progression-free survival (PFS) and overall survival (OS). Compared
      with the patients without HBV infection (PFS: 95% CI 47.915 to 55.640; OS: 95% CI
      81.324 to 86.858), the PFS and OS of the patients with chronic active HBV
      infection were significantly shorter (PFS: 95% CI 9.424 to 42.589, P < 0.001; OS:
      95% CI 42.840 to 82.259, P = 0.006). The study demonstrated that the sustained
      HBV replication in patients with chronic active HBV infection could be a key
      factor that influences the prognosis of NHL patients after chemotherapy, and thus
      may provide information for designing rational clinical treatments for NHL
      patients with different HBV infection statuses and improve the treatment efficacy
      and prognosis. 

PMID- 23861970
TI  - The co-expression pattern of odorant binding proteins and olfactory receptors
      identify distinct trichoid sensilla on the antenna of the malaria mosquito
      Anopheles gambiae.
AB  - The initial steps of odorant recognition in the insect olfactory system involve
      odorant binding proteins (OBPs) and odorant receptors (ORs). While large families
      of OBPs have been identified in the malaria vector A. gambiae, little is known
      about their expression pattern in the numerous sensory hairs of the female
      antenna. We applied whole mount fluorescence in Situ hybridization (WM-FISH) and
      fluorescence immunohistochemistry (WM-FIHC) to investigate the sensilla co
      expression of eight A. gambiae OBPs (AgOBPs), most notably AgOBP1 and AgOBP4,
      which all have abundant transcripts in female antenna. WM-FISH analysis of female
      antennae using AgOBP-specific probes revealed marked differences in the number of
      cells expressing each various AgOBPs. Testing combinations of AgOBP probes in two
      color WM-FISH resulted in distinct cellular labeling patterns, indicating a
      combinatorial expression of AgOBPs and revealing distinct AgOBP requirements for
      various functional sensilla types. WM-FIHC with antisera to AgOBP1 and AgOBP4
      confirmed expression of the respective proteins by support cells and demonstrated
      a location of OBPs within sensilla trichodea. Based on the finding that AgOBP1
      and AgOBP4 as well as the receptor type AgOR2 are involved in the recognition of
      indole, experiments were performed to explore if the AgOBP-types and AgOR2 are co
      expressed in distinct olfactory sensilla. Applying two-color WM-FISH with AgOBP
      specific probes and probes specific for AgOR2 revealed a close association of
      support cells bearing transcripts for AgOBP1 and AgOBP4 and neurons with a
      transcript for the receptor AgOR2. Moreover, combined WM-FISH/-FIHC approaches
      using an AgOR2-specific riboprobe and AgOBP-specific antisera revealed the
      expression of the "ligand-matched" AgOBP1, AgOBP4 and AgOR2 to single trichoid
      hairs. This result substantiates the notion that a specific response to indole is
      mediated by an interplay of the proteins. 

PMID- 23861971
TI  - Unlipidated outer membrane protein Omp16 (U-Omp16) from Brucella spp. as nasal
      adjuvant induces a Th1 immune response and modulates the Th2 allergic response to
      cow's milk proteins.
AB  - The discovery of novel mucosal adjuvants will help to develop new formulations to
      control infectious and allergic diseases. In this work we demonstrate that U
      Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an
      inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues.
      Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA)
      increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG
      and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed
      in a mouse model of food allergy. U-Omp16 i.n. administration during
      sensitization ameliorated the hypersensitivity responses of sensitized mice upon
      oral exposure to Cow's Milk Protein (CMP), decreased clinical signs, reduced anti
      CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity.
      Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag
      formulations. 

PMID- 23861972
TI  - When are statins cost-effective in cardiovascular prevention? A systematic review
      of sponsorship bias and conclusions in economic evaluations of statins.
AB  - BACKGROUND: We examined sponsorship of published cost-effectiveness analyses of
      statin use for cardiovascular (CV) prevention, and determined whether the funding
      source is associated with study conclusions. METHODS AND FINDINGS: We searched
      PubMed/MEDLINE (up to June 2011) to identify cost-effectiveness analyses of
      statin use for CV prevention reporting outcomes as incremental costs per quality
      adjusted life years (QALY) and/or life years gained (LYG). We examined
      relationships between the funding source and the study conclusions by means of
      tests of differences between proportions. Seventy-five studies were included.
      Forty-eight studies (64.0%) were industry-sponsored. Fifty-two (69.3%) articles
      compared statins versus non-active alternatives. Secondary CV prevention
      represented 42.7% of articles, followed by primary CV prevention (38.7%) and both
      (18.7%). Overall, industry-sponsored studies were much less likely to report
      unfavourable or neutral conclusions (0% versus 37.1%; p<0.001). For primary CV
      prevention, the proportion with unfavourable or neutral conclusions was 0% for
      industry-sponsored studies versus 57.9% for non-sponsored studies (p<0.001).
      Conversely, no statistically significant differences were identified for studies
      evaluating secondary CV prevention (0% versus 12.5%; p=0.222). Incremental costs
      per QALY/LYG estimates reported in industry-sponsored studies were generally more
      likely to fall below a hypothetical willingness-to-pay threshold of US $50,000.
      CONCLUSIONS: Our systematic analysis suggests that pharmaceutical industry
      sponsored economic evaluations of statins have generally favored the cost
      effectiveness profile of their products particularly in primary CV prevention.

PMID- 23861973
TI  - Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription
      via DNA damage accumulation.
AB  - The Hedgehog pathway is activated in various types of malignancies. We previously
      reported that inhibition of SMO or GLI prevents osteosarcoma growth in vitro and
      in vivo. Recently, it has been reported that arsenic trioxide (ATO) inhibits
      cancer growth by blocking GLI transcription. In this study, we analyzed the
      function of ATO in the pathogenesis of osteosarcoma. Real-time PCR showed that
      ATO decreased the expression of Hedgehog target genes, including PTCH1, GLI1, and
      GLI2, in human osteosarcoma cell lines. WST-1 assay and colony formation assay
      revealed that ATO prevented osteosarcoma growth. These findings show that ATO
      prevents GLI transcription and osteosarcoma growth in vitro. Flow cytometric
      analysis showed that ATO promoted apoptotic cell death. Comet assay showed that
      ATO treatment increased accumulation of DNA damage. Western blot analysis showed
      that ATO treatment increased the expression of gammaH2AX, cleaved PARP, and
      cleaved caspase-3. In addition, ATO treatment decreased the expression of Bcl-2
      and Bcl-xL. These findings suggest that ATO treatment promoted apoptotic cell
      death caused by accumulation of DNA damage. In contrast, Sonic Hedgehog treatment
      decreased the expression of gammaH2AX induced by cisplatin treatment. ATO re
      induced the accumulation of DNA damage attenuated by Sonic Hedgehog treatment.
      These findings suggest that ATO inhibits the activation of Hedgehog signaling and
      promotes apoptotic cell death in osteosarcoma cells by accumulation of DNA
      damage. Finally, examination of mouse xenograft models showed that ATO
      administration prevented the growth of osteosarcoma in nude mice. Because ATO is
      an FDA-approved drug for treatment of leukemia, our findings suggest that ATO is
      a new therapeutic option for treatment of patients with osteosarcoma. 

PMID- 23861974
TI  - Local inflammation exacerbates the severity of Staphylococcus aureus skin
      infection.
AB  - Staphylococcus aureus is the leading cause of skin infections. In a mouse model
      of S. aureus skin infection, we found that lesion size did not correlate with
      bacterial burden. Athymic nude mice had smaller skin lesions that contained lower
      levels of myeloperoxidase, IL-17A, and CXCL1, compared with wild type mice,
      although there was no difference in bacterial burden. T cell deficiency did not
      explain the difference in lesion size, because TCR betadelta (-/-) mice did not
      have smaller lesions, and adoptive transfer of congenic T cells into athymic nude
      mice prior to infection did not alter lesion size. The differences observed were
      specific to the skin, because mortality in a pneumonia model was not different
      between wild type and athymic nude mice. Thus, the clinical severity of S. aureus
      skin infection is driven by the inflammatory response to the bacteria, rather
      than bacterial burden, in a T cell independent manner. 

PMID- 23861975
TI  - A new transcriptional repressor of the pseudomonas aeruginosa quorum sensing
      receptor gene lasR.
AB  - Pseudomonas aeruginosa pathogenic potential is controlled via multiple regulatory
      pathways, including three quorum sensing (QS) systems. LasR is a key QS signal
      receptor since it acts as a global transcriptional regulator required for optimal
      expression of main virulence factors. P. aeruginosa modulates the QS response by
      integrating this cell density-dependent circuit to environmental and metabolic
      cues. Hence, QS also controls the adaptation to challenging environmental niches,
      such as infection sites. However, little is known about the molecular mechanisms
      connecting QS and other signalling pathways. In this work, DNA-affinity
      chromatography was used to identify new lasR transcriptional regulators. This
      approach led to the identification and functional characterization of the TetR
      like transcriptional repressor PA3699. This protein was purified and shown to
      directly bind to the lasR promoter region in vitro. The induction of PA3699
      expression in P. aeruginosa PAO1 cultures repressed lasR promoter activity and
      the production of LasR-dependent virulence factors, such as elastase, pyocyanin,
      and proteases. These findings suggest a role for PA3699 in P. aeruginosa
      pathogenicity. P. aeruginosa genome encodes at least 38 TetR-family proteins, and
      PA3699 is the eighth member of this group functionally characterized so far and
      the first one shown to bind the lasR promoter in vitro. 

PMID- 23861976
TI  - A pilot study combining a GC-sensor device with a statistical model for the
      identification of bladder cancer from urine headspace.
AB  - There is a need to reduce the number of cystoscopies on patients with haematuria.
      Presently there are no reliable biomarkers to screen for bladder cancer. In this
      paper, we evaluate a new simple in-house fabricated, GC-sensor device in the
      diagnosis of bladder cancer based on volatiles. Sensor outputs from 98 urine
      samples were used to build and test diagnostic models. Samples were taken from 24
      patients with transitional (urothelial) cell carcinoma (age 27-91 years, median
      71 years) and 74 controls presenting with urological symptoms, but without a
      urological malignancy (age 29-86 years, median 64 years); results were analysed
      using two statistical approaches to assess the robustness of the methodology. A
      two-group linear discriminant analysis method using a total of 9 time points
      (which equates to 9 biomarkers) correctly assigned 24/24 (100%) of cancer cases
      and 70/74 (94.6%) controls. Under leave-one-out cross-validation 23/24 (95.8%) of
      cancer cases were correctly predicted with 69/74 (93.2%) of controls. For partial
      least squares discriminant analysis, the correct leave-one-out cross-validation
      prediction values were 95.8% (cancer cases) and 94.6% (controls). These data are
      an improvement on those reported by other groups studying headspace gases and
      also superior to current clinical techniques. This new device shows potential for
      the diagnosis of bladder cancer, but the data must be reproduced in a larger
      study. 

PMID- 23861977
TI  - NRAS and BRAF mutations in melanoma-associated nevi and uninvolved nevi.
AB  - According to the prevailing multistep model of melanoma development, oncogenic
      BRAF or NRAS mutations are crucial initial events in melanoma development. It is
      not known whether melanocytic nevi that are found in association with a melanoma
      are more likely to carry BRAF or NRAS mutations than uninvolved nevi. By laser
      microdissection we were able to selectively dissect and genotype cells either
      from the nevus or from the melanoma part of 46 melanomas that developed in
      association with a nevus. In 25 cases we also genotyped a control nevus of the
      same patients. Available tissue was also immunostained using the BRAF(V600E)
      mutation specific antibody VE1. The BRAF(V600E) mutation was found in 63.0% of
      melanomas, 65.2% of associated nevi and 50.0% of control nevi. No significant
      differences in the distribution of BRAF or NRAS mutations could be found between
      melanoma and associated nevi or between melanoma associated nevi and control
      nevi. In concordant cases immunohistochemistry showed a higher expression
      (intensity of immunohistochemistry) of the mutated BRAF(V600E)-protein in
      melanomas compared to their associated nevi. In this series the presence of a
      BRAF- or NRAS mutation in a nevus was not associated with the risk of malignant
      transformation. Our findings do not support the current traditional model of
      stepwise tumor progression. 

PMID- 23861978
TI  - Transfection of infectious RNA and DNA/RNA layered vectors of semliki forest
      virus by the cell-penetrating peptide based reagent PepFect6.
AB  - Viral vectors have a wide variety of applications ranging from fundamental
      studies of viruses to therapeutics. Recombinant viral vectors are usually
      constructed using methods of reverse genetics to obtain the genetic material of
      the viral vector. The physicochemical properties of DNA and RNA make them unable
      to access cells by themselves, and they require assistance to achieve
      intracellular delivery. Non-viral delivery vectors can be used for this purpose
      if they enable efficient intracellular delivery without interfering with the
      viral life cycle. In this report, we utilize Semliki Forest virus (genus
      alphavirus) based RNA and DNA vectors to study the transfection efficiency of the
      non-viral cell-penetrating peptide-based delivery vector PepFect6 in comparison
      with that of the cationic liposome-based Lipofectamine 2000, and assess their
      impact on viral replication. The optimal conditions for transfection were
      determined for both reagents. These results demonstrate, for the first time, the
      ability of PepFect6 to transport large (13-19 kbp) constructs across the cell
      membrane. Curiously, DNA molecules delivered using the PepFect6 reagent were
      found to be transported to the cell nucleus approximately 1.5 hours later than
      DNA molecules delivered using the Lipofectamine 2000 reagent. Finally, although
      both PepFect6 and Lipofectamine 2000 reagents can be used for alphavirus
      research, PepFect6 is preferred because it does not induce changes in the normal
      cellular phenotype and it does not affect the normal replication-infection cycle
      of viruses in previously transfected cells. 

PMID- 23861980
TI  - Correlation analysis connects cancer subtypes.
AB  - We provided a cross-tissue comparative analysis of between-subtype molecular
      commonality for ovarian cancer, breast cancer, hepatocellular carcinoma, glioma,
      lung squamous carcinoma and nasopharyngeal carcinoma. Our analysis showed that
      molecular subtypes with similar phenotype or similar clinical outcome could be
      correlated by their transcriptional profile and pathway profile. Pathway
      dysregulation across multiple cancer subtypes was also revealed by Gene Set
      Enrichment Analysis. Dysregulation of 'complement and coagulation cascades' was
      observed in a total of eleven subtypes across five tissues, implicating that the
      role of this process in personalized immune-based therapy may be worth further
      exploring. 

PMID- 23861979
TI  - Imaging lymphatic system in breast cancer patients with magnetic resonance
      lymphangiography.
AB  - OBJECTIVE: To investigate the feasibility of gadolinium (Gd) contrast-enhanced
      magnetic resonance lymphangiography (MRL) in breast cancer patients within a
      typical clinical setting, and to establish a Gd-MRL protocol and identify
      potential MRL biomarkers for differentiating metastatic from non-metastatic lymph
      nodes. MATERIALS AND METHODS: 32 patients with unilateral breast cancer were
      enrolled and divided into 4 groups of 8 patients. Groups I, II, and III received
      1.0, 0.5, and 0.3 ml of intradermal contrast; group IV received two 0.5 ml doses
      of intradermal contrast. MRL images were acquired on a 3.0 T system and evaluated
      independently by two radiologists for the number and size of enhancing lymph
      nodes, lymph node contrast uptake kinetics, lymph vessel size, and contrast
      enhancement patterns within lymph nodes. RESULTS: Group III patients had a
      statistically significant decrease in the total number of enhancing axillary
      lymph nodes and lymphatic vessels compared to all other groups. While group IV
      patients had a statistically significant faster time to reach the maximum peak
      enhancement over group I and II (by 3 minutes), there was no other statistically
      significant difference between imaging results between groups I, II, and IV. 27
      out of 128 lymphatic vessels (21%) showed dilatation, and all patients with
      dilated lymphatic vessels were pathologically proven to have metastases. Using
      the pattern of enhancement defects as the sole criterion for identifying
      metastatic lymph nodes during Gd-MRL interpretation, and using histopathology as
      the gold standard, the sensitivity and specificity were estimated to be 86% and
      95%, respectively. CONCLUSION: Gd-MRL can adequately depict the lymphatic system,
      can define sentinel lymph nodes, and has the potential to differentiate between
      metastatic and non-metastatic lymph nodes in breast cancer patients.

PMID- 23861981
TI  - Population-specific use of the same tool-assisted alarm call between two wild
      orangutan populations (Pongo pygmaeus wurmbii) indicates functional arbitrariness
      [corrected].
AB  - Arbitrariness is an elementary feature of human language, yet seldom an object of
      comparative inquiry. While arbitrary signals for the same function are relatively
      frequent between animal populations across taxa, the same signal with arbitrary
      functions is rare and it remains unknown whether, in parallel with human speech,
      it may involve call production in animals. To investigate this question, we
      examined a particular orangutan alarm call - the kiss-squeak - and two variants -
      hand and leaf kiss-squeaks. In Tuanan (Central Kalimantan, Indonesia), the
      acoustic frequency of unaided kiss-squeaks is negatively related to body size.
      The modified variants are correlated with perceived threat and are hypothesized
      to increase the perceived body size of the sender, as the use of a hand or leaves
      lowers the kiss-squeak's acoustic frequency. We examined the use of these
      variants in the same context in another orangutan population of the same sub
      species and with partially similar habitat at Cabang Panti (West Kalimantan,
      Indonesia). Identical analyses of data from this site provided similar results
      for unaided kiss-squeaks but dissimilar results for hand and leaf kiss-squeaks.
      Unaided kiss-squeaks at Cabang Panti were emitted as commonly and showed the same
      relationship to body size as in Tuanan. However, at Cabang Panti, hand kiss
      squeaks were extremely rare, while leaf-use neither conveyed larger body size nor
      was related to perceived threat. These findings indicate functional discontinuity
      between the two sites and therefore imply functional arbitrariness of leaf kiss
      squeaks. These results show for the first time the existence of animal signals
      involving call production with arbitrary function. Our findings are consistent
      with previous studies arguing that these orangutan call variants are socially
      learned and reconcile the role of gestures and calls within evolutionary theories
      based on common ancestry for speech and music. 

PMID- 23861982
TI  - Risk factors for progressive visual field loss in primary angle-closure glaucoma:
      a retrospective cohort study.
AB  - PURPOSE: To investigate risk factors associated with progressive visual field
      (VF) loss in primary angle closure glaucoma (PACG). METHODS: We retrospectively
      reviewed medical record of PACG patients who had >=5 reliable VF examinations
      (central 24-2 threshold test, Humphrey Field Analyzer) and >=2 years of follow
      up. Each VF was scored using Collaborative Initial Glaucoma Treatment Study
      system. Progression was defined if 3 consecutive follow-up VF tests had an
      increased score of >=3 above the mean of the first 2 VF scores. Factors
      associated with VF progression were evaluated by Cox proportional hazards models.
      RESULTS: A total of 89 eyes from 89 patients (mean age, 69.8 +/- 7.9 years), who
      received a mean of 6.9 +/- 2.3 VF tests (mean deviation at initial, -8.1 +/- 4.4
      dB) with a mean follow-up of 63.9 +/- 23.9 months were included. VF progression
      was detected in 9 eyes (10%). The axial length (AL), anterior chamber depth, and
      intraocular pressure (IOP) in patients with and without progression were 22.5 +/-
      0.6 and 23.1 +/- 0.9 mm, 2.5 +/- 0.3 and 2.5 +/- 0.3 mm, 14.8 +/- 2.4 and 14.3 +/
      2.3 mm Hg, respectively. AL was the only factor associated with progression in
      both Cox proportional hazards univariate (p = 0.031) and multivariate models (p =
      0.023). CONCLUSION: When taking into account age, IOP, follow-up period, and
      number of VF tests, a shorter AL is the only factor associated with VF
      progression in this cohort of Chinese patients with PACG. Further studies are
      warranted to verify the role of AL in progressive VF loss in PACG.

PMID- 23861983
TI  - Isospora suis in an epithelial cell culture system - an in vitro model for sexual
      development in coccidia.
AB  - Coccidian parasites are of major importance in animal production, public health
      and food safety. The most frequently used representative in basic research on
      this group is Toxoplasma gondii. Although this parasite is well investigated
      there is no adequate in vitro model for its sexual development available and
      knowledge on this important life cycle phase is therefore scarce. The use of
      Isosporasuis, a sister taxon to T. gondii and the causative agent of piglet
      coccidiosis, could provide a solution for this. In the present study an in vitro
      model for neonatal porcine coccidiosis in cells representative for the in vivo
      situation in the piglet gut was developed and evaluated. The parasite development
      was investigated by light and transmission electron microscopy and optimum
      culture conditions were evaluated. Intestinal porcine epithelial cells (IPEC-J2)
      adequately representing the natural host cells supported the development of all
      endogenous life cycle stages of I. suis, including gametocytes and oocysts. A
      concentration of 5% fetal calf serum in the culture medium led to highest
      gametocyte densities on day 12 post infection. Low infection doses (<=1
      sporozoite for 100 host cells) were best for oocyst and gametocyte development.
      The presented system can also be used for immunostaining with established
      antibodies developed against T. gondii (in our case, anti-TgIMC3 antibodies
      directed against the inner membrane complex 3). The complete life cycle of I.
      suis in a cell line representing the natural host cell type and species provides
      a unique model among coccidian parasites and can be used to address a wide range
      of topics, especially with regard to the sexual development of coccidia. 

PMID- 23861984
TI  - Conspecific and heterospecific cues override resource quality to influence
      offspring production.
AB  - Animals live in an uncertain world. To reduce uncertainty, animals use cues that
      can encode diverse information regarding habitat quality, including both non
      social and social cues. While it is increasingly appreciated that the sources of
      potential information are vast, our understanding of how individuals integrate
      different types of cues to guide decision-making remains limited. We
      experimentally manipulated both resource quality (presence/absence of cactus
      fruit) and social cues (conspecific juveniles, heterospecific juveniles, no
      juveniles) for a cactus-feeding insect, Narniafemorata (Hemiptera: Coreidae), to
      ask how individuals responded to resource quality in the presence or absence of
      social cues. Cactus with fruit is a high-quality environment for juvenile
      development, and indeed we found that females laid 56% more eggs when cactus
      fruit was present versus when it was absent. However, when conspecific or
      heterospecific juveniles were present, the effects of resource quality on egg
      numbers vanished. Overall, N. femorata laid approximately twice as many eggs in
      the presence of heterospecifics than alone or in the presence of conspecifics.
      Our results suggest that the presence of both conspecific and heterospecific
      social cues can disrupt responses of individuals to environmental gradients in
      resource quality. 

PMID- 23861985
TI  - A reporter screen in a human haploid cell line identifies CYLD as a constitutive
      inhibitor of NF-kappaB.
AB  - The development of forward genetic screens in human haploid cells has the
      potential to transform our understanding of the genetic basis of cellular
      processes unique to man. So far, this approach has been limited mostly to the
      identification of genes that mediate cell death in response to a lethal agent,
      likely due to the ease with which this phenotype can be observed. Here, we
      perform the first reporter screen in the near-haploid KBM7 cell line to identify
      constitutive inhibitors of NF-kappaB. CYLD was the only currently known negative
      regulator of NF-kappaB to be identified, thus uniquely distinguishing this gene.
      Also identified were three genes with no previous known connection to NF-kappaB.
      Our results demonstrate that reporter screens in haploid human cells can be
      applied to investigate the many complex signaling pathways that converge upon
      transcription factors. 

PMID- 23861986
TI  - Field evaluation of the Cepheid GeneXpert Chlamydia trachomatis assay for
      detection of infection in a trachoma endemic community in Tanzania.
AB  - PURPOSE: To determine the sensitivity, specificity, and field utility of the
      Cepheid GeneXpert Chlamydia trachomatis (CT) Assay (GeneXpert) for ocular
      chlamydia infection compared to Roche Amplicor CT assay (Amplicor). METHODS: In a
      trachoma-endemic community in Kongwa Tanzania, 144 children ages 0 to 9 were
      surveyed to assess clinical trachoma and had two ocular swabs taken. One swab was
      processed at Johns Hopkins University, Baltimore MD, using Amplicor, (Roche
      Molecular Diagnostics) and the other swab was processed at a field station in
      Kongwa using the GeneXpert Chlamydia trachomatis/Neisseria gonorrhoeae assay
      (Cepheid). The sensitivity and specificity of GeneXpert was compared to the
      Amplicor assay. RESULTS: Of the 144 swabs taken the prevalence of follicular
      trachoma by clinical exam was 43.7%, and by evidence of infection according to
      Amplicor was 28.5%. A total of 17 specimens (11.8%) could not be processed by
      GeneXpert in the field due to lack of sample volume, other specimen issues or
      electricity failure. The sensitivity of GeneXpert when compared to Amplicor was
      100% and the specificity was 95%. The GeneXpert test identified more positives in
      individuals with clinical trachoma than Amplicor, 55% versus 52%. CONCLUSION: The
      GeneXpert test for C. trachomatis performed with high sensitivity and specificity
      and demonstrated excellent promise as a field test for trachoma control.

PMID- 23861987
TI  - Transcriptomic profiling of diverse Aedes aegypti strains reveals increased basal
      level immune activation in dengue virus-refractory populations and identifies
      novel virus-vector molecular interactions.
AB  - Genetic variation among Aedes aegypti populations can greatly influence their
      vector competence for human pathogens such as the dengue virus (DENV). While
      intra-species transcriptome differences remain relatively unstudied when compared
      to coding sequence polymorphisms, they also affect numerous aspects of mosquito
      biology. Comparative molecular profiling of mosquito strain transcriptomes can
      therefore provide valuable insight into the regulation of vector competence. We
      established a panel of A. aegypti strains with varying levels of susceptibility
      to DENV, comprising both laboratory-maintained strains and field-derived colonies
      collected from geographically distinct dengue-endemic regions spanning South
      America, the Caribbean, and Southeast Asia. A comparative genome-wide gene
      expression microarray-based analysis revealed higher basal levels of numerous
      immunity-related gene transcripts in DENV-refractory mosquito strains than in
      susceptible strains, and RNA interference assays further showed different degrees
      of immune pathway contribution to refractoriness in different strains. By
      correlating transcript abundance patterns with DENV susceptibility across our
      panel, we also identified new candidate modulators of DENV infection in the
      mosquito, and we provide functional evidence for two potential DENV host factors
      and one potential restriction factor. Our comparative transcriptome dataset thus
      not only provides valuable information about immune gene regulation and usage in
      natural refractoriness of mosquito populations to dengue virus but also allows us
      to identify new molecular interactions between the virus and its mosquito vector.

PMID- 23861988
TI  - The use of NanoTrap particles as a sample enrichment method to enhance the
      detection of Rift Valley Fever Virus.
AB  - BACKGROUND: Rift Valley Fever Virus (RVFV) is a zoonotic virus that is not only
      an emerging pathogen but is also considered a biodefense pathogen due to the
      threat it may cause to public health and national security. The current state of
      diagnosis has led to misdiagnosis early on in infection. Here we describe the use
      of a novel sample preparation technology, NanoTrap particles, to enhance the
      detection of RVFV. Previous studies demonstrated that NanoTrap particles lead to
      both 100 percent capture of protein analytes as well as an improvement of more
      than 100-fold in sensitivity compared to existing methods. Here we extend these
      findings by demonstrating the capture and enrichment of viruses. RESULTS:
      Screening of NanoTrap particles indicated that one particle, NT53, was the most
      efficient at RVFV capture as demonstrated by both qRT-PCR and plaque assays.
      Importantly, NT53 capture of RVFV resulted in greater than 100-fold enrichment
      from low viral titers when other diagnostics assays may produce false negatives.
      NT53 was also capable of capturing and enhancing RVFV detection from serum
      samples. RVFV that was inactivated through either detergent or heat treatment was
      still found bound to NT53, indicating the ability to use NanoTrap particles for
      viral capture prior to transport to a BSL-2 environment. Furthermore, both NP-40
      lysed virus and purified RVFV RNA were bound by NT53. Importantly, NT53 protected
      viral RNA from RNase A degradation, which was not observed with other
      commercially available beads. Incubation of RVFV samples with NT53 also resulted
      in increased viral stability as demonstrated through preservation of infectivity
      at elevated temperatures. Finally, NanoTrap particles were capable of capturing
      VEEV and HIV, demonstrating the broad applicability of NanoTrap particles for
      viral diagnostics. CONCLUSION: This study demonstrates NanoTrap particles are
      capable of capturing, enriching, and protecting RVFV virions. Furthermore, the
      use of NanoTrap particles can be extended to a variety of viruses, including VEEV
      and HIV.

PMID- 23861989
TI  - Molecular epidemiology reveals genetic diversity amongst isolates of the
      Cryptococcus neoformans/C. gattii species complex in Thailand.
AB  - To gain a more detailed picture of cryptococcosis in Thailand, a retrospective
      study of 498 C. neoformans and C. gattii isolates has been conducted. Among
      these, 386, 83 and 29 strains were from clinical, environmental and veterinary
      sources, respectively. A total of 485 C. neoformans and 13 C. gattii strains were
      studied. The majority of the strains (68.9%) were isolated from males (mean age
      of 37.97 years), 88.5% of C. neoformans and only 37.5% of C. gattii strains were
      from HIV patients. URA5-RFLP and/or M13 PCR-fingerprinting analysis revealed that
      the majority of the isolates were C. neoformans molecular type VNI regardless of
      their sources (94.8%; 94.6% of the clinical, 98.8% of the environmental and 86.2%
      of the veterinary isolates). In addition, the molecular types VNII (2.4%; 66.7%
      of the clinical and 33.3% of the veterinary isolates), VNIV (0.2%; 100%
      environmental isolate), VGI (0.2%; 100% clinical isolate) and VGII (2.4%; 100%
      clinical isolates) were found less frequently. Multilocus Sequence Type (MLST)
      analysis using the ISHAM consensus MLST scheme for the C. neoformans/C. gattii
      species complex identified a total of 20 sequence types (ST) in Thailand
      combining current and previous data. The Thai isolates are an integrated part of
      the global cryptococcal population genetic structure, with ST30 for C. gattii and
      ST82, ST83, ST137, ST141, ST172 and ST173 for C. neoformans being unique to
      Thailand. Most of the C. gattii isolates were ST7 = VGIIb, which is identical to
      the less virulent minor Vancouver island outbreak genotype, indicating Thailand
      as a stepping stone in the global spread of this outbreak strain. The current
      study revealed a greater genetic diversity and a wider range of major molecular
      types being present amongst Thai cryptococcal isolates than previously reported. 

PMID- 23861990
TI  - Face time: educating face transplant candidates.
AB  - OBJECTIVE: Face transplantation is the innovative application of microsurgery and
      immunology to restore appearance and function to those with severe facial
      disfigurements. Our group aims to establish a multidisciplinary education program
      that can facilitate informed consent and build a strong knowledge base in
      patients to enhance adherence to medication regimes, recovery, and quality of
      life. METHODS: We analyzed handbooks from our institution's solid organ
      transplant programs to identify topics applicable to face transplant patients.
      The team identified unique features of face transplantation that warrant
      comprehensive patient education. RESULTS: We created a 181-page handbook to
      provide subjects interested in pursuing transplantation with a written source of
      information on the process and team members and to address concerns they may
      have. While the handbook covers a wide range of topics, it is easy to understand
      and visually appealing. CONCLUSIONS: Face transplantation has many unique aspects
      that must be relayed to the patients pursuing this novel therapy. Since
      candidates lack third-party support groups and programs, the transplant team must
      provide an extensive educational component to enhance this complex process.
      PRACTICE IMPLICATIONS: As face transplantation continues to develop, programs
      must create sound education programs that address patients' needs and concerns to
      facilitate optimal care.

PMID- 23861991
TI  - Posterior reversible encephalopathy syndrome in a renal transplanted patient.
AB  - PATIENT: Male, 28 FINAL DIAGNOSIS: Posterior reversible encephalopathy syndrome
      Symptoms: Headache * pain around umblical region * seizures * visual disturbances
      MEDICATION: Mycophenolate mofetil Clinical Procedure: Treatment of parasitosis *
      antiepileptic treatment * control of hypertension * changing mycophenolate
      mofetil to everolimus Specialty: Transplantology. OBJECTIVE: Unusual or
      unexpected effect of treatment. BACKGROUND: Posterior reversible encephalopathy
      syndrome (PRES) is characterized by reversible neurological findings with
      clinical hallmarks such as headache, confusion, seizures, cortical visual
      disturbances, and other focal neurological signs. CASE REPORT: A 28-year-old male
      patient was hospitalized secondary to diarrhea and abdominal pain. He had renal
      transplantation due to renal amyloidosis secondary to familial Mediterranean
      fever (FMF). In his clinical follow-up, he had seizures, hemiparesis, blurred
      vision, and vomited an Ascaris lumbricoides. MRI results led to diagnosis of
      PRES. Mycophenolate mofetil was changed to everolimus, his systolic blood was
      pressure kept below 140 mm hg, and his intestinal parasitosis was treated. During
      follow-up, he had no pain and no diarrhea. His neurological symptoms turned to
      normal within 48 hours and neuroradiological findings returned to normal within 2
      weeks. CONCLUSIONS: PRES is a rare disorder of unknown incidence in renal
      transplantation patients. Early diagnosis is very important to prevent
      irreversible neurological sequelae. PRES is totally reversible with cessation of
      the offending agent, rapid control of hypertension, and treatment of the
      underlying disease. For early diagnosis and to reduce morbidity and mortality,
      stool sample examination should be made in patients taking immunosuppressive
      drugs.

PMID- 23861992
TI  - The janus of oxidative stress signaling in different pathophysiological
      conditions.

PMID- 23861993
TI  - Efficacy of fish oil on serum of TNF alpha , IL-1 beta , and IL-6 oxidative
      stress markers in multiple sclerosis treated with interferon beta-1b.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal
      plaques of demyelination and tissue injury in the central nervous system.
      Oxidative stress is also thought to promote tissue damage in multiple sclerosis.
      Current research findings suggest that omega-3 polyunsaturated fatty acids
      (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA)
      contained in fish oil may have anti-inflammatory, antioxidant, and
      neuroprotective effects. The aim of the present work was to evaluate the efficacy
      of fish oil supplementation on serum proinflammatory cytokine levels, oxidative
      stress markers, and disease progression in MS. 50 patients with relapsing
      remitting MS were enrolled. The experimental group received orally 4 g/day of
      fish oil for 12 months. The primary outcome was serum TNF alpha levels; secondary
      outcomes were IL-1 beta 1b, IL-6, nitric oxide catabolites, lipoperoxides,
      progression on the expanded disability status scale (EDSS), and annualized
      relapses rate (ARR). Fish oil treatment decreased the serum levels of TNF alpha ,
      IL-1 beta , IL-6, and nitric oxide metabolites compared with placebo group (P <=
      0.001). There was no significant difference in serum lipoperoxide levels during
      the study. No differences in EDSS and ARR were found. CONCLUSION: Fish oil
      supplementation is highly effective in reducing the levels of cytokines and
      nitric oxide catabolites in patients with relapsing-remitting MS.

PMID- 23861995
TI  - Infrared thermography in pain medicine.

PMID- 23861994
TI  - Chrononutrition against oxidative stress in aging.
AB  - Free radicals and oxidative stress have been recognized as important factors in
      the biology of aging and in many age-associated degenerative diseases.
      Antioxidant systems deteriorate during aging. It is, thus, considered that one
      way to reduce the rate of aging and the risk of chronic disease is to avoid the
      formation of free radicals and reduce oxidative stress by strengthening
      antioxidant defences. Phytochemicals present in fruits, vegetables, grains, and
      other foodstuffs have been linked to reducing the risk of major oxidative stress
      induced diseases. Some dietary components of foods possess biological activities
      which influence circadian rhythms in humans. Chrononutrition studies have shown
      that not only the content of food, but also the time of ingestion contributes to
      the natural functioning of the circadian system. Dietary interventions with
      antioxidant-enriched foods taking into account the principles of chrononutrition
      are of particular interest for the elderly since they may help amplify the
      already powerful benefits of phytochemicals as natural instruments with which to
      prevent or delay the onset of common age-related diseases. 

PMID- 23861997
TI  - Herpes zoster vaccination.
AB  - Varicella (chickenpox) is a highly contagious airborne disease caused by primary
      infection with the varicella zoster virus (VZV). Following the resolution of
      chickenpox, the virus can remain dormant in the dorsal sensory and cranial
      ganglion for decades. Shingles (herpes zoster [HZ]) is a neurocutaneous disease
      caused by reactivation of latent VZV and may progress to postherpetic neuralgia
      (PHN), which is characterized by dermatomal pain persisting for more than 120
      days after the onset of HZ rash, or "well-established PHN", which persist for
      more than 180 days. Vaccination with an attenuated form of VZV activates specific
      T-cell production, thereby avoiding viral reactivation and development of HZ. It
      has been demonstrated to reduce the occurrence by approximately 50-70%, the
      duration of pain of HZ, and the frequency of subsequent PHN in individuals aged
      >= 50 years in clinical studies. However, it has not proved efficacious in
      preventing repeat episodes of HZ and reducing the severity of PHN, nor has its
      long-term efficacy been demonstrated. The most frequent adverse reactions
      reported for HZ vaccination were injection site pain and/or swelling and
      headache. In addition, it should not be administrated to children, pregnant
      women, and immunocompromised persons or those allergic to neomycin or any
      component of the vaccine. 

PMID- 23861996
TI  - Painful boney metastases.
AB  - Boney metastasis may lead to terrible suffering from debilitating pain. The most
      likely malignancies that spread to bone are prostate, breast, and lung. Painful
      osseous metastases are typically associated with multiple episodes of
      breakthrough pain which may occur with activities of daily living, weight
      bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain
      episodes are rapid in onset and short in duration and 44% of episodes are
      unpredictable. Treatment strategies include: analgesic approaches with "triple
      opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy,
      interventional and surgical approaches, steroids, radiation (external beam
      radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation,
      cryoablation), and intrathecal analgesics. 

PMID- 23861998
TI  - Sonoanatomic variation of pes anserine bursa.
AB  - BACKGROUND: The pes anserine bursa lies beneath the pes anserine tendon, which is
      the insertional tendon of the sartorius, gracilis, and semitendinosus muscles on
      the medial side of the tibia, but it can lie in different sites in the medial
      knee. Accurate diagnosis of the position of the bursa is critical for diagnostic
      and therapeutic goals. The aim of this study was to evaluate sonoanatomic
      variations of the pes anserine bursa in the medial knee. METHODS: One hundred
      seventy asymptomatic volunteers were enrolled in this study. Using ultrasound
      imaging (transverse approach, 7-13 MHz linear array probe) the sonoanatomic
      position of the pes anserine bursa and its relation to the pes anserine tendon
      were evaluated. Additionally, we evaluated the sonoanatomic variation of the
      saphenous nerve. RESULTS: The position of the pes anserine bursa was between the
      medial collateral ligament and the pes anserine tendons in 21.2%/18.8%
      (males/females) of subjects; between the pes anserine tendons and the tibia in
      67.1%/64.7% (m/f); and among the pes anserine tendons in 8.2%/12.9% (m/f). No
      significant differences in the position of the bursa existed between males and
      females. The saphenous nerve was found within the pes anserine tendons in
      77.6%/74.1% (m/f) of subjects, but outside the pes anserine tendons in
      18.8%/15.3% (m/f). Visibility of sonoanatomic structures was not related to
      either gender or BMI. CONCLUSIONS: Ultrasound provides very accurate information
      about variations in the pes anserine bursa and the saphenous nerve. This suggests
      that our proposed ultrasound method can be a reliable guide to facilitate
      approaches to the medial knee for diagnostic and therapeutic objectives.

PMID- 23861999
TI  - The Effects of Pre-emptive Administration of Ketamine and norBNI on Pain
      Behavior, c-Fos, and Prodynorphin Protein Expression in the Rat Spinal Cord after
      Formalin-induced Pain Is Modulated by the DREAM Protein.
AB  - BACKGROUND: We investigated the effects of pre-emptive administration of ketamine
      and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin
      proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after
      formalin injection. METHODS: Eighty-four male Sprague Dawley rats were divided
      into 4 major groups consisting of control rats (C) (n = 12), rats given only
      formalin injections (F) (n = 24), and rats treated with pre-emptive
      administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The
      non-control groups were further divided into subgroups consisting of rats that
      were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin
      injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats
      were sacrificed and the spinal cords (L4-L5 sections) were removed for
      immunohistochemistry and Western blot analysis. RESULTS: The pain behavior
      response was reduced in the K+F group compared to the other groups during the
      second phase of the formalin pain response. We detected an increase in the
      nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient
      decrease in the N+F group at 2 hours; however, it increased at 4 hours after
      injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity
      (PLI) neurons decreased in the K+F group but increased in the N+F group at 2
      hours after injection. While FLI decreased, PLI increased in all groups at 4
      hours after injection. CONCLUSIONS: We suggest that NMDA and kappa opioid
      receptors can modulate DREAM protein expression, which can affect pain behavior
      and protein transcriptional processes at 2 hours and bring about either harmful
      or protective effects at 4 hours after formalin injection.

PMID- 23862000
TI  - Comparison of morphine and tramadol in transforaminal epidural injections for
      lumbar radicular pain.
AB  - BACKGROUND: Transforaminal epidural steroid injections are known to reduce
      inflammation by inhibiting synthesis of various proinflammatory mediators and
      have been used increasingly. The anti-inflammatory properties of opioids are not
      as fully understood but apparently involve antagonism sensory neuron excitability
      and pro-inflammatory neuropeptide release. To date, no studies have addressed the
      efficacy of transforaminal epidural morphine in patients with radicular pain, and
      none have directly compared morphine with a tramadol for this indication. The aim
      of this study was to compare morphine and tramadol analgesia when administered
      via epidural injection to patients with lumbar radicular pain. METHODS: A total
      of 59 patients were randomly allocated to 1 of 2 treatment groups and followed
      for 3 months after procedure. Each patient was subjected to C-arm guided
      transforaminal epidural injection (TFEI) of an affected nerve root. As assigned,
      patients received either morphine sulfate (2.5 mg/2.5 ml) or tramadol (25 mg/0.5
      ml) in combination with 0.2% ropivacaine (1 ml). Using numeric rating scale was
      subsequently rates at 2 weeks and 3 months following injection for comparison
      with baseline. RESULTS: Both groups had significantly lower mean pain scores at 2
      weeks and at 3 months after treatment, but outcomes did not differ significantly
      between groups. CONCLUSIONS: TFEI of an opioid plus local anesthetic proved
      effective in treating radicular pain. Although morphine surpassed tramadol in
      pain relief scores, the difference was not statistically significant.

PMID- 23862001
TI  - The Effect of Low-dose Ketamine on Post-caesarean Delivery Analgesia after Spinal
      Anesthesia.
AB  - BACKGROUND: Ketamine, an N-methyl-D-aspartate receptor antagonist, might play a
      role in postoperative analgesia, but its effect on postoperative pain after
      caesarean section varies with study design. We investigated whether the
      preemptive administration of low-dose intravenous ketamine decreases
      postoperative opioid requirement and postoperative pain in parturients receiving
      intravenous fentanyl with patient-controlled analgesia (PCA) following caesarean
      section. METHODS: Spinal anesthesia was performed in 40 parturients scheduled for
      elective caesarean section. Patients in the ketamine group received a 0.5 mg/kg
      ketamine bolus intravenously followed by 0.25 mg/kg/h continuous infusion during
      the operation. The control group received the same volume of normal saline.
      Immediately after surgery, the patients were connected to a PCA device set to
      deliver 25-ug fentanyl as an intravenous bolus with a 15-min lockout interval and
      no continuous dose. Postoperative pain was assessed using the cumulative dose of
      fentanyl and visual analog scale (VAS) scores at 2, 6, 24, and 48 h
      postoperatively. RESULTS: Significantly less fentanyl was used in the ketamine
      group 2 h after surgery (P = 0.033), but the difference was not significant at 6,
      12, and 24 h postoperatively. No significant differences were observed between
      the VAS scores of the two groups at 2, 6, 12, and 24 h postoperatively.
      CONCLUSIONS: Intraoperative low-dose ketamine did not have a preemptive analgesic
      effect and was not effective as an adjuvant to decrease opioid requirement or
      postoperative pain score in parturients receiving intravenous PCA with fentanyl
      after caesarean section.

PMID- 23862002
TI  - Orthostatic intolerance ambulation in patients using patient controlled
      analgesia.
AB  - BACKGROUND: Opioid analgesics are widely used to reduce postoperative pain and to
      enhance post-operative recovery. However, orthostatic intolerance (OI) induced by
      opioid containing intravenous patient controlled analgesia (IPCA) may hinder
      postoperative recovery. This study investigated factors that affect OI in
      patients receiving IPCA for postoperative pain control. METHODS: OI was instantly
      evaluated at the time of first ambulation in 175 patients taking opioid
      containing IPCA after open and laparoscopic subtotal gastrectomies. Patients were
      classified as having OI if they experienced dizziness, nausea/vomiting, blurred
      vision, headache, somnolence and syncope. Factors contributing to OI were
      assessed with logistic regression analysis. RESULTS: Out of 175 patients, 61
      (52.6%) male and 44 (74.6%) female patients experienced OI at the time of first
      ambulation. The frequency of OI related symptoms were dizziness (97, 55.4%),
      nausea (46, 26.3%), headache (9, 5.1%), blurred vision (3, 1.7%) and vomiting (2,
      1.1%). Significant risk factors for OI were gender (P=0.002) and total amount of
      opioids administered (P=0.033). CONCLUSIONS: The incidence of OI is significantly
      higher in male than in female patients and is influenced by the opioid dose.

PMID- 23862004
TI  - Successful treatment of abdominal cutaneous entrapment syndrome using ultrasound
      guided injection.
AB  - There are various origins for chronic abdominal pain. About 10-30% of patients
      with chronic abdominal pain have abdominal wall pain. Unfortunately, abdominal
      wall pain is not thought to be the first origin of chronic abdominal pain;
      therefore, patients usually undergo extensive examinations, including diagnostic
      laparoscopic surgery. Entrapment of abdominal cutaneous nerves at the muscular
      foramen of the rectus abdominis is a rare cause of abdominal wall pain. If
      abdominal wall pain is considered in earlier stage of chronic abdominal pain,
      unnecessary invasive procedures are not required and patients will reach symptom
      free condition as soon as the diagnosis is made. Here, we report a case of
      successful treatment of a patient with abdominal cutaneous nerve entrapment
      syndrome by ultrasound guided injection therapy. 

PMID- 23862003
TI  - Motor Weakness after Caudal Epidural Injection Using the Air-acceptance Test.
AB  - Air injected into the epidural space may spread along the nerves of the
      paravertebral space. Depending on the location of the air, neurologic
      complications such as multiradicular syndrome, lumbar root compression, and even
      paraplegia may occur. However, cases of motor weakness caused by air bubbles
      after caudal epidural injection are rare. A 44-year-old female patient received a
      caudal epidural injection after an air-acceptance test. Four hours later, she
      complained of motor weakness in the right lower extremity and numbness of the S1
      dermatome. Magnetic resonance imaging showed no anomalies other than an air
      bubble measuring 13 mm in length and 0.337 ml in volume positioned near the right
      S1 root. Her symptoms completely regressed within 48 hours. 

PMID- 23862005
TI  - Concomitant Glomus Tumor with CRPS in the Hand.
AB  - Glomus tumors are benign tumors that account for 1% to 5% of all soft tissue
      tumors of the hand and are characterized by a triad of sensitivity to cold,
      localized tenderness and severe paroxysmal pain. Paroxysmal pain is a symptom
      common not only in glomus tumors but also in CRPS, and the hand is one of the
      commonly affected sites in patients with both glomus tumors and CRPS. Therefore,
      it is not easy to clinically diagnose glomus tumors superimposed on already
      affected region of CRPS patients. We report a case of glomus tumor concomitantly
      originating with CRPS at the hand. 

PMID- 23862006
TI  - Secondary erythromelalgia - a case report -.
AB  - Erythromelalgia is a rare neurovascular pain syndrome characterized by a triad of
      redness, increased temperature, and burning pain primarily in the extremities.
      Erythromelalgia can present as a primary or secondary form, and secondary
      erythromelalgia associated with a myeloproliferative disease such as essential
      thrombocythemia often responds dramatically to aspirin therapy, as in the present
      case. Herein, we describe a typical case of a 48-year-old woman with secondary
      erythromelalgia linked to essential thrombocythemia in the unilateral hand. As
      this case demonstrates, detecting and visualizing the hyperthermal area through
      infrared thermography of an erythromelalgic patient can assist in diagnosing the
      patient, assessing the therapeutic results, and understanding the disease course
      of erythromelalgia. 

PMID- 23862007
TI  - A case of postural orthostatic tachycardia syndrome associated with migraine and
      fibromyalgia.
AB  - Postural orthostatic tachycardia syndrome (POTS) refers to the presence of
      orthostatic intolerance with a heart rate (HR) increment of 30 beats per minute
      (bpm) or an absolute HR of 120 bpm or more. There are sporadic reports of the
      autonomic nervous system dysfunction in migraine and fibromyalgia. We report a
      case of POTS associated with migraine and fibromyalgia. The patient was managed
      with multidisciplinary therapies involving medication, education, and exercise
      which resulted in symptomatic improvement. We also review the literature on the
      association between POTS, migraine, and fibromyalgia. 

PMID- 23862008
TI  - Effect of collimation on radiation exposure and image quality.

PMID- 23862009
TI  - Mirror therapy as an alternative treatment for phantom limb pain: a short
      literature review.

PMID- 23862010
TI  - Relieving pain with acupuncture after inguinal surgeries.

PMID- 23862011
TI  - Vitamin e, an antioxidant, as a possible therapeutic agent for treating pain.

PMID- 23862013
TI  - On fundamental cellular processes for emergence of collective epithelial
      movement.
AB  - In all animals, collective cell movement is an essential process in many events,
      including wound healing and embryonic development. However, our understanding of
      what characterizes the emergence of multicellular collective behavior is still
      far from complete. In this article we showed the fundamental cellular processes
      that drive collective cell movement by means of integrated approaches, including
      precise quantification measurements and mathematical modeling of measured data.
      First, we observed the dependence of the collective behaviors of cultured human
      skin cells on Ca(2+) concentrations. When the culturing area confined by a PDMS
      sheet was suddenly expanded by removing the sheet, the group of cells moved to
      the expanded area with higher collectivity at higher Ca(2+) concentrations. Next,
      we quantitatively measured cellular responses to the Ca(2+) treatments, such as
      cell growth, cell division, and the strength of intercellular adhesion. Using a
      femtosecond-laser-based assay, an original method for estimating intercellular
      adhesion, we found that the strength of intercellular adhesion has an
      approximately 13-fold range in our treatments. Incorporating the quantitative
      data into a mathematical model, we then confirmed that the model well reproduced
      the multicellular behaviors we observed, demonstrating that the strength of
      intercellular adhesion sufficiently determines the generation of collective cell
      movement. Finally, we performed extensive numerical experiments, and the results
      suggested that the emergence of collective cell movement is derived by an optimal
      balance between the strength of intercellular adhesion and the intensity of cell
      migration. 

PMID- 23862014
TI  - Requirement of LIM domains for the transient accumulation of paxillin at damaged
      stress fibres.
AB  - Cells recognize and respond to changes in intra- and extracellular mechanical
      conditions to maintain their mechanical homeostasis. Linear contractile bundles
      of actin filaments and myosin II known as stress fibres (SFs) mediate mechanical
      signals. Mechanical cues such as excessive stress driven by myosin II and/or
      external force may damage SFs and induce the local transient accumulation of SF
      repair complexes (zyxin and VASP) at the damaged sites. Using an atomic force
      microscope mounted on a fluorescence microscope, we applied mechanical damage to
      cells expressing fluorescently tagged cytoskeletal proteins and recorded the
      subsequent mobilization of SF-repair complexes. We found that a LIM protein,
      paxillin, transiently accumulated at the damaged sites earlier than zyxin, while
      paxillin knockdown did not affect the kinetics of zyxin translocation. The C
      terminal half of paxillin, comprising four-tandem LIM domains, can still
      translocate to damaged sites on SFs, suggesting that the LIM domain is essential
      for the mechanosensory function of paxillin. Our findings demonstrate a crucial
      role of the LIM domain in mechanosensing LIM proteins. 

PMID- 23862012
TI  - Foxc1 is required by pericytes during fetal brain angiogenesis.
AB  - Brain pericytes play a critical role in blood vessel stability and blood-brain
      barrier maturation. Despite this, how brain pericytes function in these different
      capacities is only beginning to be understood. Here we show that the forkhead
      transcription factor Foxc1 is expressed by brain pericytes during development and
      is critical for pericyte regulation of vascular development in the fetal brain.
      Conditional deletion of Foxc1 from pericytes and vascular smooth muscle cells
      leads to late-gestation cerebral micro-hemorrhages as well as pericyte and
      endothelial cell hyperplasia due to increased proliferation of both cell types.
      Conditional Foxc1 mutants do not have widespread defects in BBB maturation,
      though focal breakdown of BBB integrity is observed in large, dysplastic vessels.
      qPCR profiling of brain microvessels isolated from conditional mutants showed
      alterations in pericyte-expressed proteoglycans while other genes previously
      implicated in pericyte-endothelial cell interactions were unchanged. Collectively
      these data point towards an important role for Foxc1 in certain brain pericyte
      functions (e.g. vessel morphogenesis) but not others (e.g. barriergenesis). 

PMID- 23862015
TI  - hsa-miR29b, a critical downstream target of non-canonical Wnt signaling, plays an
      anti-proliferative role in non-small cell lung cancer cells via targeting MDM2
      expression.
AB  - In non-small cell lung cancer cell lines, activation of beta-catenin independent
      signaling, via Wnt7a/Frizzled9 signaling, leads to reversal of cellular
      transformation, reduced anchorage-independent growth and induction of epithelial
      differentiation. miRNA expression profiling on a human lung adenocarcinoma cell
      line (A549) identified hsa-miR29b as an important downstream target of
      Wnt7a/Frizzled9 signaling. We show herein that hsa-miR29b expression is lost in
      non-small cell lung cancer (NSCLC) cell lines and stimulation of beta-catenin
      independent signaling, via Wnt7a expression, in NSCLC cell lines results in
      increased expression of hsa-miR29b. Surprisingly, we also identify specific
      regulation of hsa-miR29b by Wnt7a but not by Wnt3, a ligand for beta-catenin
      dependent signaling. Interestingly, knockdown of hsa-miR29b was enough to
      abrogate the tumor suppressive effects of Wnt7a/Frizzled9 signaling in NSCLC
      cells, suggesting that hsa-miR29b is an important mediator of beta-catenin
      independent signaling. Finally, we show for the first time that hsa-miR29b plays
      an important role as a tumor suppressor in lung cancer by targeting murine double
      mutant 2 (MDM2), revealing novel nodes for Wnt7a/Frizzled9-mediated regulation of
      NSCLC cell proliferation. 

PMID- 23862016
TI  - Targeting of vasoactive intestinal peptide receptor 2, VPAC2, a secretin family G
      protein coupled receptor, to primary cilia.
AB  - Primary cilia protrude from the cell surface of many cell types in the human body
      and function as cellular antennae via ciliary membrane localized receptors.
      Neurons and glial cells in the brain possess primary cilia, and the malfunction
      of primary cilia may contribute to neurological deficits present in many cilia
      associated disorders. Several rhodopsin family G-protein coupled receptors
      (GPCRs) are specifically localized to a subset of neuronal primary cilia.
      However, whether other family GPCRs target to neuronal cilia and whether glial
      primary cilia harbor any GPCRs are not known. We conducted a screening of GPCRs
      to determine their ability to target to primary cilia, and identified a secretin
      family member, Vasoactive Intestinal Receptor 2 (VPAC2), as a novel ciliary GPCR.
      Here, we show that endogenous VPAC2 targets to primary cilia in various brain
      regions, including the suprachiasmatic nuclei and the thalamus. Surprisingly,
      VPAC2 not only localizes to neuronal cilia but also to glial cilia. In addition,
      we show that VPAC2's C-terminus is both necessary and sufficient for its ciliary
      targeting and we define a novel ciliary targeting signal: the tetrapeptide RDYR
      motif in the C-terminus of VPAC2. Furthermore, we demonstrate that VPAC2 ciliary
      targeting is dependent on Tubby, the BBSome (a complex of Bardet-Biedl syndrome
      proteins) and the BBSome targeting factor, Arl6.

PMID- 23862017
TI  - Predisposition to apoptosis in keratin 8-null liver is related to inactivation of
      NF-kappaB and SAPKs but not decreased c-Flip.
AB  - Keratin 8 and 18 (K8/K18) are major intermediate filament proteins of liver
      hepatocytes. They provide mechanical and nonmechanical stability, thereby
      protecting cells from stress. Hence, K8-null mice are highly sensitive to Fas
      mediated liver cell apoptosis. However, the role of c-Flip protein in K8-null
      related susceptibility to liver injury is controversial. Here we analyzed c-Flip
      protein expression in various K8 or K18 null/mutant transgenic livers and show
      that they are similar in all analyzed transgenic livers and that previously
      reported c-Flip protein changes are due to antibody cross-reaction with mouse
      K18. Furthermore, analysis of various apoptosis- or cell survival-related
      proteins demonstrated that inhibition of phosphorylation of NF-kappaB and various
      stress activated protein kinases (SAPKs), such as p38 MAPK, p44/42 MAPK and
      JNK1/2, is related to the higher sensitivity of K8-null hepatocytes whose nuclear
      NF-kappaB is rapidly depleted through Fas-mediated apoptosis. Notably, we found
      that NF-kappaB and the studied protein kinases are associated with the K8/K18
      complex and are released upon phosphorylation. Therefore, interaction of keratins
      with cell survival-related protein kinases and transcription factors is another
      important factor for hepatocyte survival. 

PMID- 23862018
TI  - transparent, a gene affecting stripe formation in Zebrafish, encodes the
      mitochondrial protein Mpv17 that is required for iridophore survival.
AB  - In the skin of adult zebrafish, three pigment cell types arrange into alternating
      horizontal stripes, melanophores in dark stripes, xanthophores in light
      interstripes and iridophores in both stripes and interstripes. The analysis of
      mutants and regeneration studies revealed that this pattern depends on
      interactions between melanophores and xanthophores; however, the role of
      iridophores in this process is less understood. We describe the adult viable and
      fertile mutant transparent (tra), which shows a loss or strong reduction of
      iridophores throughout larval and adult stages. In addition, in adults only the
      number of melanophores is strongly reduced, and stripes break up into spots.
      Stripes in the fins are normal. By cell transplantations we show that tra acts
      cell-autonomously in iridophores, whereas the reduction in melanophores in the
      body occurs secondarily as a consequence of iridophore loss. We conclude that
      differentiated iridophores are required for the accumulation and maintenance of
      melanophores during pigment pattern formation. The tra mutant phenotype is caused
      by a small deletion in mpv17, an ubiquituously expressed gene whose protein
      product, like its mammalian and yeast homologs, localizes to mitochondria.
      Iridophore death might be the result of mitochondrial dysfunction, consistent
      with the mitochondrial DNA depletion syndrome observed in mammalian mpv17
      mutants. The specificity of the tra phenotype is most likely due to redundancy
      after gene multiplication, making this mutant a valuable model to understand the
      molecular function of Mpv17 in mitochondria. 

PMID- 23862019
TI  - Receptor guanylyl cyclase Gyc76C is required for invagination, collective
      migration and lumen shape in the Drosophila embryonic salivary gland.
AB  - The Drosophila embryonic salivary gland is formed by the invagination and
      collective migration of cells. Here, we report on a novel developmental role for
      receptor-type guanylyl cyclase at 76C, Gyc76C, in morphogenesis of the salivary
      gland. We demonstrate that Gyc76C and downstream cGMP-dependent protein kinase 1
      (DG1) function in the gland and surrounding mesoderm to control invagination,
      collective migration and lumen shape. Loss of gyc76C resulted in glands that
      failed to invaginate, complete posterior migration and had branched lumens.
      Salivary gland migration defects of gyc76C mutant embryos were rescued by
      expression of wild-type gyc76C specifically in the gland or surrounding mesoderm,
      whereas invagination defects were rescued primarily by expression in the gland.
      In migrating salivary glands of gyc76C mutant embryos, integrin subunits
      localized normally to gland-mesoderm contact sites but talin localization in the
      surrounding circular visceral mesoderm and fat body was altered. The
      extracellular matrix protein, laminin, also failed to accumulate around the
      migrating salivary gland of gyc76C mutant embryos, and gyc76C and laminin
      genetically interacted in gland migration. Our studies suggest that gyc76C
      controls salivary gland invagination, collective migration and lumen shape, in
      part by regulating the localization of talin and the laminin matrix. 

PMID- 23862020
TI  - CEH-20/Pbx and UNC-62/Meis function upstream of rnt-1/Runx to regulate asymmetric
      divisions of the C. elegans stem-like seam cells.
AB  - Caenorhabditis elegans seam cells divide in the stem-like mode throughout larval
      development, with the ability to both self-renew and produce daughters that
      differentiate. Seam cells typically divide asymmetrically, giving rise to an
      anterior daughter that fuses with the hypodermis and a posterior daughter that
      proliferates further. Previously we have identified rnt-1 (a homologue of the
      mammalian cancer-associated stem cell regulator Runx) as being an important
      regulator of seam development, acting to promote proliferation; rnt-1 mutants
      have fewer seam cells whereas overexpressing rnt-1 causes seam cell hyperplasia.
      We isolated the interacting CEH-20/Pbx and UNC-62/Meis TALE-class transcription
      factors during a genome-wide RNAi screen for novel regulators of seam cell
      number. Animals lacking wild type CEH-20 or UNC-62 display seam cell hyperplasia,
      largely restricted to the anterior of the worm, whereas double mutants have many
      additional seam cells along the length of the animal. The cellular basis of the
      hyperplasia involves the symmetrisation of normally asymmetric seam cell
      divisions towards the proliferative stem-like fate. The hyperplasia is completely
      suppressed in rnt-1 mutants, and rnt-1 is upregulated in ceh-20 and unc-62
      mutants, suggesting that CEH-20 and UNC-62 function upstream of rnt-1 to limit
      proliferative potential to the appropriate daughter cell. In further support of
      this we find that CEH-20 is asymmetrically localised in seam daughters following
      an asymmetric division, being predominantly restricted to anterior nuclei whose
      fate is to differentiate. Thus, ceh-20 and unc-62 encode crucial regulators of
      seam cell division asymmetry, acting via rnt-1 to regulate the balance between
      proliferation and differentiation. 

PMID- 23862021
TI  - The C-terminus of S. pombe DDK subunit Dfp1 is required for meiosis-specific
      transcription and cohesin cleavage.
AB  - The DDK complex is a conserved kinase complex, consisting of a catalytic subunit,
      Hsk1 (Cdc7), and its regulatory subunit Dfp1 (Dbf4). This kinase is essential for
      DNA replication. In this work, we show that dfp1-r35, which truncates the Dfp1 C
      terminus zinc finger, causes severe meiotic defects, including reduced spore
      viability, reduced formation of programmed double strand breaks, altered
      expression of meiotic genes, and disrupted chromosome segregation. There is a
      high frequency of dyad formation. Mutants are also defective in the
      phosphorylation and degradation of the meiotic cohesion, Rec8, resulting in a
      failure to proceed through the MII division. These defects are more pronounced in
      a haploid meiosis model than in a normal diploid meiosis. Thus, several critical
      meiotic functions are linked specifically to the C-terminus of Dfp1, which may
      target specific substrates for phosphorylation by Hsk1. 

PMID- 23862022
TI  - Ninein is essential for the maintenance of the cortical progenitor character by
      anchoring the centrosome to microtubules.
AB  - The mammalian cerebral cortex develops from proliferative apical progenitor cells
      (APs) that exhibit cell cycle-dependent nuclear movement (interkinetic nuclear
      migration; INM), which may be important for efficient and continuous production
      of neurons. The Pax6 transcription factor plays a major role in INM by regulating
      various downstream molecules. We have previously observed abnormal INM and
      unstable localization of the centrosome in APs of the Pax6 homozygous mutant rat
      embryo. To understand the mechanisms of INM, we focused on the centrosomes of
      APs. One of the centrosomal proteins, ninein, is specifically localized in the
      centrosome of APs. We observed a dramatic downregulation of ninein in APs of the
      Pax6 mutant. Moreover, knockdown of ninein by RNAi induced ectopic distribution
      of reduced numbers of BrdU-positive (S-phase) and PH3-positive (M-phase) cells.
      Furthermore, time-lapsed imaging demonstrated that knockdown of ninein in vivo
      induced abnormal INM. Finally, we observed impaired microtubule regrowth in
      neural progenitors taken from Pax6 homozygous mutant rat embryos, which was
      recovered by via ninein overexpression. We also found that ninein knockdown
      enlarged the surface size area of apical endfeet of the APs. Our results suggest
      that ninein plays a role in the molecular machinery essential for INM by
      connecting microtubules to the centrosome. 

PMID- 23862023
TI  - Olfactory ensheathing glia are required for embryonic olfactory axon targeting
      and the migration of gonadotropin-releasing hormone neurons.
AB  - Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin
      releasing hormone (GnRH) neurons to enter the embryonic forebrain, resulting in
      anosmia and sterility. Sox10 mutations have been associated with Kallmann's
      syndrome phenotypes, but their effect on olfactory system development is unknown.
      We recently showed that Sox10 is expressed by neural crest-derived olfactory
      ensheathing cells (OECs). Here, we demonstrate that in homozygous
      Sox10(lacZ/lacZ) mouse embryos, OEC differentiation is disrupted; olfactory axons
      accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor
      neurons express the maturation marker OMP (most likely owing to the failure of
      axonal targeting). Furthermore, GnRH neurons clump together in the periphery and
      a smaller proportion enters the forebrain. Our data suggest that human Sox10
      mutations cause Kallmann's syndrome by disrupting the differentiation of OECs,
      which promote embryonic olfactory axon targeting and hence olfactory receptor
      neuron maturation, and GnRH neuron migration to the forebrain. 

PMID- 23862024
TI  - Accreditation of Graduate Medical Education Programmes: One size fits all-or does
      it?

PMID- 23862026
TI  - The asthma cost in oman.
AB  - OBJECTIVES: This study evaluates the direct costs of treating asthma in Oman.
      METHODS: Asthma prevalence and unit cost estimates were based on results from a
      panel using the Delphi technique, and were applied to the total Omani population
      aged 5 and older to obtain the number of people diagnosed with asthma. The
      estimates from the Delphi exercise were multiplied by the percentage of patients
      using government facilities to estimate the number of asthma patients managed in
      Oman. Treatment costs were also calculated using data from the Delphi exercise
      and the Asthma Insights and Reality for the Gulf and Near East study (reported in
      Omani riyals [OMR] and US dollars [USD]). RESULTS: The prevalence of asthma was
      estimated to be 7.3% of adults (n = 96,470) and 12.7% of children (n = 58,344).
      Of these, 95% of both adults and children were estimated to be using government
      healthcare facilities. Inpatient visits accounted for the largest proportion of
      total direct costs (55%), followed by emergency room and outpatient visits (25%
      and 20%, respectively) and medications (<0.2%). The annual cost of treatment
      excluding medications, was OMR 34,273,696 (USD 89,111,609) for adults and OMR
      27,014,735 (USD 70,238,311) for children. Including medications, the total annual
      direct cost of asthma treatment was estimated to be over OMR 61,500,294 (USD
      159,900,761). CONCLUSION: Given the high medical expenditures associated with
      facility visits relative to the lower medication costs, the focus of Oman's
      asthma cost savings should be on improving asthma control rather than reducing
      medication costs.

PMID- 23862025
TI  - Customised, Individualised Treatment of Metastatic Non-Small-Cell Lung Carcinoma
      (NSCLC).
AB  - A series of phase II and randomised phase III trials in Asia and Europe have
      confirmed recently that advanced stage non-small-cell lung carcinoma patients
      with adenocarcinoma subtypes harbouring specific mutations when subjected to
      targeted therapy experience equivalent survival outcomes as those treated with
      chemotherapy and are spared from its side effects. The concept of chemotherapy
      for all is fading, and therapy optimisation has emerged as a paradigm shift in
      treatment. This article briefly describes cellular mechanisms involved in lung
      carcinogenesis which provide a molecular basis for targeted therapy. Advances in
      molecular biology have improved our understanding of mechanisms involved in
      primary or secondary drug resistance. Evolving biomarkers of prognostic and
      predictive importance, and the impact of translational research on outcomes are
      also covered. A marker is considered prognostic if it predicts the outcome,
      regardless of the treatment, and predictive if it predicts the outcome of a
      specific therapy. 

PMID- 23862027
TI  - Vitamin d status and anthropometric indices of an omani study population.
AB  - OBJECTIVES: Serum 25-hydroxyvitamin D [25(OH)D] concentrations reflect vitamin D
      status, with deficiency implicated as causative of many diseases. This study
      assessed vitamin D status and anthropometric indices in a sample of healthy
      Omanis. METHODS: Serum 25(OH)D concentrations were measured by high performance
      liquid chromatography in 206 healthy Omanis, aged 18-55 years (mean age: men
      31.1, women 26.8) in Muscat, Oman. Of this number, 95% indicated that they had
      never taken vitamin D supplements. Findings were compared with published values
      for populations domiciled in more northerly latitudes. Classical procedures were
      used to determine global obesity (body mass index [BMI]), and central obesity
      determined by waist circumference, waist-to-hip ratio (WHR), and waist-to-height
      ratio. RESULTS: Women, as compared to men, had markedly lower concentrations of
      25(OH)D. Applying the cut-off point of serum 25(OH)D levels at 50 nmol/L, the
      prevalence of vitamin D deficiency in the study population was 87.5%; this was
      higher than the rates reported for the British, and European-, Hispanic-, and
      African-Americans. At a BMI cut-point of >=30 kg/m(2), the prevalence of obesity
      was 14.6%; this was lower than the rates reported for European-, Hispanic-, and
      African-Americans. Levels of 25(OH) D increased relative to age and obesity. WHR
      was the main predictor of 25(OH)D levels. CONCLUSION: The striking vitamin D
      deficiency seen in the study population, relative to more northerly populations,
      may be linked to sun avoidance, inadequate dietary vitamin D, and virtual non
      intake of supplemental vitamin D. Age and male-gender determined the status of
      vitamin D and of obesity.

PMID- 23862028
TI  - Predictors of Human Immunodeficiency Virus Knowledge among Jordanian Youths.
AB  - OBJECTIVES: Understanding factors associated with the level of human
      immunodeficiency virus (HIV) knowledge acquisition is crucial to inform
      preventative programmes for young people. This study examines predictors of HIV
      knowledge among Jordanian youths. METHODS: A cross-sectional survey was conducted
      among 8,129 youths aged between 14 and 25 years randomly selected from schools
      representing each of the 12 governorates of Jordan. A total of 50% of respondents
      were female and, on average, 17 years old. Participants completed a self
      administered questionnaire covering sociodemographic characteristics, HIV
      knowledge, gender awareness, exposure to and favourable attitudes toward risky
      behaviours. RESULTS: On a 13-item HIV knowledge test, participants answered an
      average of 7 questions correctly (mean = 7.21; standard deviation = 2.63). Female
      respondents from rural areas demonstrated significantly lower levels of HIV
      knowledge, while college and university students demonstrated higher levels. HIV
      knowledge differed significantly by sources of information, with peer-acquired
      information associated with more accuracy, while HIV information from parents or
      health centres was associated with a lower score. Youths with more egalitarian
      gender views also demonstrated higher knowledge levels, whereas youths approving
      of drug use showed lower levels of HIV knowledge. CONCLUSION: HIV education
      programmes in Jordan should focus on females and youths living in rural areas.
      Educational institutions have been shown to be effective in providing accurate
      information to students, while parents and health professionals should also be
      included in HIV prevention programmes in order to reduce misconceptions and raise
      the level of HIV knowledge among Jordanian youths.

PMID- 23862029
TI  - Idiopathic Granulomatous Mastitis: Diagnostic strategy and therapeutic
      implications in Omani patients.
AB  - OBJECTIVES: Idiopathic granulomatous mastitis (IGM) is a rare benign disorder of
      the breast whose aetiology is controversial, and is often misdiagnosed clinically
      and radiologically as mammary malignancy; as a result, it may be incorrectly
      treated. Although no standard treatment is available for this chronic disease,
      surgery with or without corticosteroids has been tried with controversial
      results. This study discusses the clinical presentation, diagnosis, management,
      recurrence, and follow-up data of IGM with a review of relevant literature.
      METHODS: From 2009-2012, the Breast Unit at Sultan Qaboos University Hospital,
      Oman, conducted a clinical study on 20 patients with breast lumps. Their clinical
      and radiological examinations were indeterminate, and a diagnosis of
      granulomatous mastitis was established only by histopathology. RESULTS: The
      majority of the patients were cases of unknown aetiology, who presented with a
      unilateral breast mass. A few patients had a mass with an abscess, along with
      axillary lymphadenopathy. A total of 4 patients were suspected of malignancy
      using radiology. In all patients, sterilised pus was sent for culture and
      sensitivity. Microscopy showed the characteristic pattern of granulomatous
      inflammation. All patients were treated with antibiotics for 6 weeks, and the
      mean follow-up period was 15 months (11-33 months). All patients had complete
      remission with no further recurrence. CONCLUSION: This single largest study of
      cases of IGM in Oman highlights the pitfalls in diagnosing this non-neoplastic
      disease of unknown aetiology and uncertain pathogenesis. It emphasises IGM's
      excellent response to antibiotics, which is crucial, as IGM is a disease which is
      notoriously difficult and controversial to treat.

PMID- 23862030
TI  - Reasons for Consultation among Patients attending Primary Healthcare Centres in
      Oman.
AB  - OBJECTIVES: Pathways to care or care-seeking, which translate into healthcare
      utilisation, have been investigated in many parts of the world, but there is a
      dearth of studies in the Arabian Gulf. The aim of this study was to examine the
      characteristics of attendees at primary healthcare centres in northern Oman and
      their reasons for visiting. METHODS: Face-to-face interviews were conducted with
      676 participants attending 12 primary healthcare centres between June and July
      2006. The catchment area was selected to represent the population structure in
      Oman. The 12-item questionnaire was read to every fifth eligible patient entering
      each healthcare centre for a routine appointment. Analyses were conducted using
      univariate statistics. RESULTS: About a third (n = 200; 29.6%) of the
      participants had a history of chronic illness; 231 (34%) were on regular
      medications; 211 (31%) were taking part in health education programmes; 130 (19%)
      were open to complementary medicine. The majority of the participants mentioned
      physician's advice (n = 570; 84%) as the strongest reason for seeking
      consultation. Conversely, physician's advice was strongly related to particular
      demographic factors. CONCLUSION: This observational study identified some
      characteristics and reasons for visiting healthcare facilities in northern Oman.
      These are discussed within the context of prevailing sociocultural factors. The
      implications for the prevention and detection of ill health in Oman are also
      discussed.

PMID- 23862031
TI  - Does haloperidol prophylaxis reduce ketamine-induced emergence delirium in
      children?
AB  - OBJECTIVES: Ketamine is a non-barbiturate agent with rapid action onset that
      induces profound sedation; however, some emergency physicians tend not to use
      ketamine because of the risk of emergence delirium (ED). This study aimed to
      evaluate the effectiveness of haloperidol prophylaxis in postoperative ketamine
      delirium in children. METHODS: Prospective data relating to any emergence dreams,
      delirium, hallucinations, agitation, crying, altered perceptions, and necessary
      interventions were recorded in consecutive cases of ketamine delirium in patients
      attending Mansoura University Hospital, Egypt, from June 2010 to May 2011.
      RESULTS: A total of 537 records were available for analysis. Of those, 267
      received prophylactic haloperidol (49.7%). There were significant differences
      between the two groups regarding post-anaesthetic care unit behaviour. The
      ketamine-haloperidol groups included more patients who were sleepy, calm (P
      <=0.01) and less irritable (P <=0.01), with a lower incidence of crying (P
      <=0.01) and disorientation (P <=0.01). CONCLUSION: We found that preoperative
      administration of haloperidol decreases the incidence of postoperative delirium
      in a sample of Egyptian children undergoing minor surgery. This is congruent with
      earlier work conducted in adults. This work carries great hope to decrease and
      even prevent ED in hospitalised, non-surgical patients.

PMID- 23862032
TI  - A study of adiponectin in children with diabetes mellitus.
AB  - OBJECTIVES: Adiponectin is a hormone produced by adipose tissue. It is secreted
      exclusively by adipocytes and appears to play a role in the pathophysiology of
      obesity, diabetes mellitus (DM), and its comorbidities. The aim of this study was
      to assess adiponectin levels in diabetic children with type 1 DM (T1DM) and type
      2 DM (T2DM), and to detect its prognostic role in them. METHODS: This study was
      undertaken from April to July 2011 at Minia University Children's Hospital,
      Egypt, and included 314 children aged 2-18 years divided into two patient groups.
      Group I consisted of 164 pre-diagnosed diabetic patients, further subdivided into
      Group Ia which included 142 patients with T1DM and Group Ib, 22 patients with
      T2DM; Group 2 included 150 apparently healthy children as a controls; they were
      age- and sex-matched to the diseased group. Patients were subjected to a thorough
      history taking, clinical examination, and laboratory investigations including
      assessment of HbA1c percentages, fasting C-peptide levels, lipid profiles and
      fasting serum adiponectin levels. RESULTS: Adiponectin levels did not differ
      significantly between patients with T1DM and T2DM, but it was significantly
      higher in diabetic patients than in the controls. In T1DM, adiponectin had
      positive significant correlations with the duration of the disease and waist
      circumference, while in T2DM, it had a positive significant correlation with the
      dose of insulin given and negative significant associations with diastolic blood
      pressure, cholesterol, and C-peptide levels. CONCLUSION: The results of the study
      suggest that adiponectin can play a protective role against the metabolic
      complications of DM.

PMID- 23862033
TI  - Prevalence of urinary incontinence and probable risk factors in a sample of
      kurdish women.
AB  - OBJECTIVES: The most common manifestation of pelvic floor dysfunction is urinary
      incontinence (UI) which affects 15-50% of adult women depending on the age and
      risk factors of the population studied. The aim of this study was to determine
      the probable risk factors associated with UI; the characteristics of women with
      UI; describe the types of UI, and determine its prevalence. METHODS: A cross
      sectional study was conducted between February and August 2011, in the Maternity
      Teaching Hospital of the Erbil Governorate, Kurdistan Region, northern Iraq. It
      included 1,107 women who were accompanying patients admitted to the hospital. A
      questionnaire designed by the researchers was used for data collection. A chi
      square test was used to test the significance of the association between UI and
      different risk factors. Binary logistic regression was used, considering UI as
      the dependent variable. RESULTS: The overall prevalence of UI was 51.7%. The
      prevalence of stress, urgency, and mixed UI was 5.4%, 13.3% and 33%,
      respectively. There was a significant positive association between UI and
      menopause, multiparity, diabetes mellitus (DM), chronic cough, constipation, and
      a history of gynaecological surgery, while a significant negative association was
      detected between UI and a history of delivery by both vaginal delivery and
      Caesarean section. CONCLUSION: A high prevalence of UI was detected in the
      studied sample, and the most probable risk factors were multiparity, menopausal
      status, constipation, chronic cough, and DM.

PMID- 23862034
TI  - Cost Comparison between Laparoscopic and Open Appendectomies in Children.
AB  - OBJECTIVES: Laparoscopic appendectomy (LA) for children has become very popular
      and is routinely performed in most health care centres around the world. The cost
      of surgical procedures is always a concern for patients and health care
      providers. This study compares, the total cost of open appendectomy (OA) with LA
      in children who required an appendectomy for acute appendicitis. Suitable and
      safe cost-effective techniques were also explored to reduce the cost of these
      procedures. METHODS: The medical records of all the children (ranging between 0
      and 12 years) at Sultan Qaboos University Hospital in Oman, who required OA or LA
      from June 2009 to July 2011, were reviewed. RESULTS: LA were performed in 75
      patients while OA were done in 34. Patients from the OA and LA groups were age-
      and gender-matched. The average operative time was 76 minutes for LA and 49
      minutes for OA (P <0.001) while the average hospital stay was 3.14 days for LA
      and 2.15 days for OA (P = 0.08). The average cost of the two procedures was Omani
      riyals (OMR) 534 for LA and OMR 343 for OA (P = 0.00). The complication rate
      following procedures was lower in the case of LA, however this was not
      statistically significant (LA = 8% versus OA = 11.7 %, P = 0.32). CONCLUSION: LA
      are costlier procedures than OA, however they are as safe as OA, and do not
      increase morbidity or the duration of hospital stay.

PMID- 23862035
TI  - The role of wrist magnetic resonance arthrography in diagnosing triangular
      fibrocartilage complex tears: experience at king hussein medical center, jordan.
AB  - OBJECTIVES: The aims of the study were to evaluate the role of magnetic resonance
      arthrography (MRA) of the wrist in detecting full-thickness tears of the
      triangular fibrocartilage complex (TFCC) and to compare the results of the
      magnetic resonance arthrography (MRA) with the gold standard arthroscopic
      findings. METHODS: The study was performed at King Hussein Medical Center, Amman,
      Jordan, between January 2008 and December 2011. A total of 42 patients (35 males
      and 7 females) who had ulnar-sided wrist pain and clinical suspicions of TFCC
      tears were included in the study. All patients underwent wrist magnetic resonance
      arthrography (MRA) and then a wrist arthroscopy. The results of MRA were compared
      with the arthroscopic findings. RESULTS: After comparison with the arthroscopic
      findings, the MRA had three false-negative results (sensitivity = 93%) and no
      false-positive results. A total of 39 patients were able to return to work.
      Satisfaction was high in 38 of the patients and 33 had satisfactory pain relief.
      The sensitivity of the wrist MRA in detecting TFCC full-thickness tears was 93%
      (39), and specificity was 80% (16/20). The overall accuracy of wrist arthroscopy
      in detecting a full-thickness tear of the TFCC in our study was 85% (29/34).
      CONCLUSION: These results illustrate the role of wrist MRA in assessing the TFCC
      pathology and suggest its use as the first imaging technique, following a plain X
      ray, in evaluating patients with chronic ulnar side wrist pain with suspected
      TFCC injuries.

PMID- 23862036
TI  - Job Stress and Burnout among Academic Career Anaesthesiologists at an Egyptian
      University Hospital.
AB  - OBJECTIVES: There is compelling evidence that anaesthesiology is a stressful
      occupation and, when this stressful occupation is associated with an academic
      career, the burnout level is high. This study aimed to assess the predictors and
      prevalence of stress and burnout, associated sociodemographic characteristics,
      and job-related features. METHODS: A cross-sectional survey study was carried out
      at Mansoura University Hospital in Egypt among 98 anaesthesiologists who had
      academic careers. The English version of the Maslach Burnout Inventory-Human
      Services Survey (MBI-HSS) scale and the Workplace Stress Scale of the American
      Institute of Stress were used to measure job stress and burnout. Data were
      analysed according to the guidelines for data processing and an analysis of the
      scales used. RESULTS: The participation rate of this study was 73.1%, where 69.4%
      were encountering job stress, while 62.2% experienced emotional exhaustion, 56.1%
      depersonalisation, and 58.2% reduced personal capacity. There was a significant
      positive correlation between job stress and MBI-HSS subscales. Residents and
      assistant lecturers were the most affected group. The strongest significant
      single predictor of all burnout dimensions was a lack of job support. CONCLUSION:
      Stress and burnout among academic anaesthesiologists were caused by the lack of
      job support; this was especially true among residents and assistant lecturers. We
      can conclude that a well-organised institutional strategy to mitigate the heavy
      professional demands of academic anaesthesiologists' will relieve their stress
      and burnout.

PMID- 23862037
TI  - Measurement of Impairment among Children with Attention Deficit Hyperactivity
      Disorder as Part of Evaluating Treatment Outcome.
AB  - This study assesses the impairment and treatment outcome of children with
      attention deficit hyperactivity disorder (ADHD) in an outpatient child psychiatry
      clinic, using multiple sources, including the Children Global Assessment Scale (C
      GAS). METHODS: A total of 20 children, aged 4 to 16 years, were recruited
      serially in 2010 from the Child Psychiatric Unit of the Psychiatric Hospital,
      Manama, Bahrain. The children received a diagnosis of ADHD using the Diagnostic
      and Statistical Manual of Mental Disorders Text Revision (DSM-IV-TR). The
      children were assessed with the C-GAS by a blinded investigator, initially at the
      beginning of the treatment and then one year later. RESULTS: The parents of the
      patients reported improvement in all cases; the improvement in impairment after
      one year, assessed using the C-GAS, was significant for all of the cases (P =
      0.001) and low for those with comorbidity (P = 0.07). CONCLUSION: Measurement of
      improvement using the C-GAS was a suitable method of collecting data, and hence
      should be included in routine clinical practice for both ADHD diagnosis and
      outcome measurement.

PMID- 23862038
TI  - One in three: congenital bent bone disease and intermittent hyperthermia in three
      siblings with stuve-wiedemann syndrome.
AB  - Stuve-Wiedemann syndrome (STWS) is a rare disorder characterised by congenital
      bowing of the long bones, contractures of the joints, neonatal onset of
      respiratory distress, sucking and swallowing difficulties, dysautonomia
      presenting as episodic hyperthermia, and usually an early death. Three siblings
      from a consanguineous marriage presented with similar clinical features over 16
      years. STWS was established with their last child at the beginning of 2012. All
      the children exhibited the onset of STWS in the neonatal period with fever and
      generalised hypotonia. Examinations of all the infants revealed camptodactyly,
      micrognathia, bent long bones with wide metaphyses, and hypotonia. Only the
      second affected child had myotonia, demonstrated by electromyography. Unusual
      pyrexia as a presenting feature in this syndrome needs early recognition so that
      extensive and elaborate investigations can be avoided. The disorder is usually
      caused by a mutation in the leukaemia inhibitory factor receptor gene. 

PMID- 23862039
TI  - Implications of a Chr7q21.11 Microdeletion and the Role of the PCLO Gene in
      Developmental Delay.
AB  - We report here a 4-year-old boy with global developmental delay who was referred
      for karyotyping and fragile X studies. A small interstitial deletion on
      chromosome 7 at band 7q21 was detected in all cells examined. Subsequent
      molecular karyotype analysis gave the more detailed result of a 6.3 Mb
      heterozygous deletion involving the interstitial chromosome region 7q21.11. In
      this relatively gene-poor region, the presynaptic cytomatrix protein, Piccolo
      (PCLO) gene appears to be the most likely candidate for copy number loss leading
      to a clinical phenotype. G-banded chromosome analysis of the parents showed this
      deletion was inherited from the father. Molecular karyotype analysis of the
      father's genome confirmed that it was the same deletion as that seen in the son;
      however, the father did not share the severity of his son's phenotype. This
      cytogenetically-visible deletion may represent another example of a chromosomal
      rearrangement conferring a variable phenotype on different family members. 

PMID- 23862040
TI  - Clinical Outcomes and Counselling Issues regarding Partial Trisomy of Terminal Xp
      in a Child with Developmental Delay.
AB  - Female carriers of balanced translocations involving an X chromosome and an
      autosome offer genetic counselling challenges. This is in view of the number of
      possible meiotic outcomes, but also due to the impact of X chromosome-localised
      genes that are no longer subject to gene silencing through the X chromosome
      inactivation centre. We present a case where delineation of the extent of X
      chromosome-localised genes on the derivative autosome using molecular karyotyping
      offers critical information in the context of genetic counselling. 

PMID- 23862041
TI  - Severe Pulmonary Involvement in Leptospirosis: Alternate antibiotics and systemic
      steroids.
AB  - Pulmonary complications in leptospirosis, though common, are often unrecognized
      in a non-endemic area. We report here a patient with leptospirosis and severe
      pulmonary involvement who was treated with meropenem (1 g every 8 hours),
      moxifloxacin (400 mg once daily), and high doses of corticosteroids. Systemic
      steroids were continued for 3 months because of persistent pulmonary lesions. 

PMID- 23862042
TI  - Lost and Found: Unusual location of a urinary tract calculus.

PMID- 23862043
TI  - Re: Health Professions Education in Oman: A contemporary perspective.

PMID- 23862044
TI  - Re: Health Professions Education in Oman: A contemporary perspective.

PMID- 23862045
TI  - Eccrine syringofibroadenoma of the eyelid.

PMID- 23862046
TI  - Re: Spectrum of AIDS Defining Opportunistic Infections in a Series of 77
      Hospitalised HIV-infected Omani Patients.

PMID- 23862047
TI  - Asymptomatic Ileal Schwannoma presenting as a Mesenteric Tumour: Case report and
      review of literature.
AB  - A schwannoma is a benign tumour which arises from the schwann cells of the
      central or peripheral nervous system. Common sites include the head and limbs; it
      is rare that this tumour arises from the gastrointestinal tract's neural plexus.
      It is even rarer to find the ileum as the site of origin. We report a patient who
      presented with a central abdominal mass which was preoperatively diagnosed as a
      mesenteric tumour. However, immunohistochemistry of the surgically-removed
      specimen proved it to be a benign ileal schwannoma. 

PMID- 23862048
TI  - Adrenal oncocytic neoplasm with uncertain malignant potential.
AB  - Adrenal oncocytic neoplasms (AONs) are a rare group of tumours with a somewhat
      uncertain natural history and clinical behaviour. Out of 46 cases of AON reported
      to date, 6 cases were histologically classified as neoplasms with uncertain
      malignant potential. We report the case of a 35-year-old male with an
      incidentally-detected large AON with mostly benign morphology and some
      characteristics which would make its behaviour uncertain. 

PMID- 23862049
TI  - Palpitations caused by a Seizure with Autonomic Features.
AB  - Palpitations are a common symptom of presentation in medical practice. They are
      usually caused by cardiac arrhythmias, psychiatric problems or other
      miscellaneous causes, such as anaemia or endocrine causes. They are rarely due to
      autonomic seizures. We report a 55-year-old woman who presented at Sultan Qaboos
      University Hospital, Oman, with recurrent episodes of palpitations. Her
      associated symptoms included breathlessness and excessive sweating, followed by a
      sensation of dizziness. During subsequent episodes, she experienced symptoms of
      rising abdominal pain followed by a loss of consciousness. Positive
      electroencephalogram findings, as well as the response of the symptoms to
      antiepileptic drugs, were strongly suggestive of temporal lobe epilepsy as the
      possible diagnosis. The fact that the cardiac investigations, performed during an
      interictal period, were unremarkable also supports the hypothesis that the
      palpitations were linked to seizures. Epilepsy should be considered as a
      differential diagnosis of palpitations, especially if the palpitations are
      episodic. 

PMID- 23862050
TI  - Large Complex Odontoma: A report of a rare entity.
AB  - Odontomas are hamartomatous lesions composed of mature enamel, dentin, and pulp,
      and may be compound or complex depending on the extent of morphodifferentiation
      or on their resemblance to normal teeth. They are the most common benign
      odontogenic tumours, constituting 22% of all odontogenic tumours of the jaw. They
      are often non-aggressive and slow growing in nature, and are usually diagnosed on
      routine radiological examinations in the second decade of life. We report the
      case of an unusually large, painless, complex odontoma, which is a rare entity.
      It was located in the left posterior mandible and was associated with missing
      1(st) and 2(nd) left mandibular molars. The diagnosis was confirmed following
      surgical excision and histopathological analysis of the lesion. 

PMID- 23862051
TI  - Maxillary first molar with two root canals.
AB  - Knowledge regarding the anatomic morphology of maxillary molars is absolutely
      essential for the success of endodontic treatment. The morphology of the
      permanent maxillary first molar has been reviewed extensively; however, the
      presence of two canals in a two-rooted maxillary first molar has rarely been
      reported in studies describing tooth and root canal anatomies. This case report
      presents a patient with a maxillary first molar with two roots and two root
      canals, who was referred to the Department of Endodontics, Tabriz University of
      Medical Sciences, Iran. 

PMID- 23862052
TI  - Sonographic detection of pseudoaneurysm in vascular injury in emergency
      department.
AB  - A 31-year-old man suffered from a stab wound to the lower extremity. The patient
      had a hard sign of a vascular injury (a diminished distal pulse) and therefore
      probably should have undergone operative repair, but refused. One week later, he
      returned to our emergency department with a painful right thigh swelling. Bedside
      sonography was used to detect a pseudoaneurysm. Emergency sonography is a fast,
      non-invasive, and rapid decision-making approach in emergency practice. 

PMID- 23862053
TI  - Development of Eimeria nieschulzi (Coccidia, Apicomplexa) Gamonts and Oocysts in
      Primary Fetal Rat Cells.
AB  - The in vitro production of gametocytes and oocysts of the apicomplexan parasite
      genus Eimeria is still a challenge in coccidiosis research. Until today, an in
      vitro development of gametocytes or oocysts had only been shown in some Eimeria
      species. For several mammalian Eimeria species, partial developments could be
      achieved in different cell types, but a development up to gametocytes or oocysts
      is still lacking. This study compares several permanent cell lines with primary
      fetal cells of the black rat (Rattus norvegicus) concerning the qualitative in
      vitro development of the rat parasite Eimeria nieschulzi. With the help of
      transgenic parasites, the developmental progress was documented. The selected
      Eimeria nieschulzi strain constitutively expresses the yellow fluorescent protein
      and a macrogamont specific upregulated red tandem dimer tomato. In the majority
      of all investigated host cells the development stopped at the second merozoite
      stage. In a mixed culture of cells derived from inner fetal organs the
      development of schizont generations I-IV, macrogamonts, and oocysts were observed
      in crypt-like organoid structures. Microgamonts and microgametes could not be
      observed and oocysts did not sporulate under air supply. By immunohistology, we
      could confirm that wild-type E. nieschulzi stages can be found in the crypts of
      the small intestine. The results of this study may be helpful for
      characterization of native host cells and for development of an in vitro
      cultivation system for Eimeria species. 

PMID- 23862054
TI  - Adults with greater weight satisfaction report more positive health behaviors and
      have better health status regardless of BMI.
AB  - BACKGROUND: Prior studies suggest that weight satisfaction may preclude changes
      in behavior that lead to healthier weight among individuals who are overweight or
      obese. OBJECTIVE: To gain a better understanding of complex relationships between
      weight satisfaction, weight-related health behaviors, and health outcomes.
      DESIGN: Cross-sectional analysis of data from the Aerobics Center Longitudinal
      Study (ACLS). PARTICIPANTS: Large mixed-gender cohort of primarily white, middle
      to-upper socioeconomic status (SES) adults with baseline examination between 1987
      and 2002 (n = 19,003). MAIN OUTCOME VARIABLES: Weight satisfaction, weight
      related health behaviors, chronic health conditions, and clinical health
      indicators. STATISTICAL ANALYSES PERFORMED: Chi-square test, t-tests, and linear
      and multivariate logistic regression. RESULTS: Compared to men, women were more
      likely to be dieting (32% women; 18% men) and had higher weight dissatisfaction.
      Men and women with greater weight dissatisfaction reported more dieting, yo-yo
      dieting, and snacking and consuming fewer meals, being less active, and having to
      eat either more or less than desired to maintain weight regardless of weight
      status. Those who were overweight or obese and dissatisfied with their weight had
      the poorest health. CONCLUSION: Greater satisfaction with one's weight was
      associated with positive health behaviors and health outcomes in both men and
      women and across weight status groups.

PMID- 23862055
TI  - Improving prediction algorithms for cardiometabolic risk in children and
      adolescents.
AB  - Clustering of abnormal metabolic traits, the Metabolic Syndrome (MetS), has been
      associated with an increased cardiovascular disease (CVD) risk. Several
      algorithms including the MetS and other risk factors exist for adults to predict
      the risk of CVD. We discuss the use of MetS scores and algorithms in an attempt
      to predict later cardiometabolic risk in children and adolescents and offer
      suggestions for developing clinically useful algorithms in this population. There
      is little consensus in how to define the MetS or to predict future CVD risk using
      the MetS and other risk factors in children and adolescents. The MetS scores and
      prediction algorithms we identified had usually not been tested against a
      clinical outcome, such as CVD, and they had not been validated in other
      populations. This makes comparisons of algorithms impossible. We suggest a simple
      two-step approach for predicting the risk of adult cardiometabolic disease in
      overweight children. It may have advantages in terms of cost-effectiveness since
      it uses simple measurements in the first step and more complex, costly
      measurements in the second step. It also takes advantage of the continuous
      distributions of the metabolic features. We suggest piloting and validating any
      new algorithms. 

PMID- 23862056
TI  - Prevalence of overweight, obesity, and thinness in Cameroon urban children and
      adolescents.
AB  - OBJECTIVE: This study examined the prevalence of thinness, overweight, and
      obesity in Cameroon children ranging from 8 to 15 years old using several
      published references as evaluation tools. METHODS: A stratified sample was used
      with eleven schools randomly selected, and data from 2689 children (52.2% girls)
      ranging from 8 to 15 years were analyzed. Weight and height were recorded and BMI
      was calculated. BMI cutoffs used to define nutritional status grades included two
      international and three national published indices which were compared to our
      database-derived cutoffs. RESULTS: A prevalence of 9.5% thinness and 12.4%
      overweight including 1.9% obesity according to international references was
      detected. A 2.2% low-weight-for-age, 5.7% low-height-for-age, and 5.2% low-weight
      for-height were identified. Overall, there were significant differences using
      calculations based on our database versus published reference values and between
      boys versus girls. CONCLUSIONS: This study demonstrates that prevalence of
      thinness, overweight, and obesity is similar to that of other leading-emerging
      countries reported within the last decade, yet it is still lower than prevalence
      in developed countries. Ethnic background and social environment have impact on
      prevalences, highlighting the importance of evaluating the Cameroon population
      based on locally derived database.

PMID- 23862057
TI  - Interdisciplinary aspects of childhood obesity and physical fitness.

PMID- 23862058
TI  - Obesity-related metabolomic analysis of human subjects in black soybean peptide
      intervention study by ultraperformance liquid chromatography and quadrupole-time
      of-flight mass spectrometry.
AB  - The present study aimed to identify key metabolites related to weight reduction
      in humans by studying the metabolic profiles of sera obtained from 34
      participants who underwent dietary intervention with black soybean peptides (BSP)
      for 12 weeks. This research is a sequel to our previous work in which the effects
      of BSP on BMI and blood composition of lipid were investigated. Sera of the study
      were subjected to ultra performance liquid chromatography and quadrupole time-of
      flight mass spectrometry (UPLC-Q-TOF-MS), and the data were analyzed using
      partial least-squares discriminate analysis (PLS-DA) score plots. Body mass index
      and percent body fat of the test group were reduced. Levels of betaine, benzoic
      acid, pyroglutamic acid, pipecolic acid, N-phenylacetamide, uric acid, l-aspartyl
      l-phenylalanine, and lysophosphatidyl cholines (lysoPCs) (C18:1, C18:2, C20:1,
      and C20:4) showed significant increases. Levels of l-proline, valine, l
      leucine/isoleucine, hypoxanthine, glutamine, l-methionine, phenylpyruvic acid,
      several carnitine derivatives, and lysoPCs (C14:0, PC16:0, C15:0, C16:0, C17:1,
      C18:0, and C22:0) were significantly decreased. In particular, lysoPC 16:0 with a
      VIP value of 12.02 is esteemed to be the most important metabolite for evaluating
      the differences between the 2 serum samples. Our result confirmed weight-lowering
      effects of BSP, accompanied by favorable changes in metabolites in the subjects'
      blood. Therefore, this research enables us to better understand obesity and
      increases the predictability of the obesity-related risk by studying metabolites
      present in the blood. 

PMID- 23862059
TI  - Estimating kidney function in the critically ill patients.
AB  - Glomerular filtration rate (GFR) is an accepted measure for assessment of kidney
      function. For the critically ill patient, creatinine clearance is the method of
      reference for the estimation of the GFR, although this is often not measured but
      estimated by equations (i.e., Cockroft-Gault or MDRD) not well suited for the
      critically ill patient. Functional evaluation of the kidney rests in serum
      creatinine (Crs) that is subjected to multiple external factors, especially
      relevant overhydration and loss of muscle mass. The laboratory method used
      introduces variations in Crs, an important fact considering that small increases
      in Crs have serious repercussion on the prognosis of patients. Efforts directed
      to stratify the risk of acute kidney injury (AKI) have crystallized in the RIFLE
      or AKIN systems, based in sequential changes in Crs or urine flow. These systems
      have provided a common definition of AKI and, due to their sensitivity, have
      meant a considerable advantage for the clinical practice but, on the other side,
      have introduced an uncertainty in clinical research because of potentially
      overestimating AKI incidence. Another significant drawback is the unavoidable
      period of time needed before a patient is classified, and this is perhaps the
      problem to be overcome in the near future. 

PMID- 23862060
TI  - Epidemiological and Pathogenic Relationship between Sleep Apnea and Ischemic
      Heart Disease.
AB  - Obstructive sleep apnea is recognized as having high prevalence and causing
      remarkable cardiovascular risk. Coronary artery disease has been associated with
      obstructive sleep apnea in many reports. The pathophysiology of coronary artery
      disease in obstructive sleep apnea patients probably includes the activation of
      multiple mechanisms, as the sympathetic activity, endothelial dysfunction,
      atherosclerosis, and systemic hypertension. Moreover, chronic intermittent
      hypoxia and oxidative stress have an important role in the pathogenesis of
      coronary disease and are also fundamental to the development of atherosclerosis
      and other comorbidities present in coronary artery diseases such as lipid
      metabolic disorders. Interestingly, the prognosis of patients with coronary
      artery disease has been associated with obstructive sleep apnea and the severity
      of sleep disordered breathing may have a direct relationship with the morbidity
      and mortality of patients with coronary diseases. Nevertheless, treatment with
      CPAP may have important effects, and recent reports have described the benefits
      of obstructive sleep apnea treatment on the recurrence of acute heart ischaemic
      events in patients with coronary artery disease. 

PMID- 23862061
TI  - Evidence-based cerebral vasospasm surveillance.
AB  - Subarachnoid hemorrhage related to aneurysmal rupture (aSAH) carries significant
      morbidity and mortality, and its treatment is focused on preventing secondary
      injury. The most common-and devastating-complication is delayed cerebral ischemia
      resulting from vasospasm. In this paper, the authors review the various
      surveillance technologies available to detect cerebral vasospasm in the days
      following aSAH. First, evidence related to the most common modalities, including
      transcranial doppler ultrasonography and computed tomography, are reviewed.
      Continuous electroencephalography and older instruments such as positron emission
      tomography, xenon-enhanced CT, and single-photon emission computed tomography are
      also discussed. Invasive strategies including brain tissue oxygen monitoring,
      microdialysis, thermal diffusion, and jugular bulb oximetry are examined. Lastly,
      near-infrared spectroscopy, a recent addition to the field, is briefly reviewed.
      Each surveillance tool carries its own set of advantages and limitations, and the
      concomitant use of multiple modalities serves to improve diagnostic sensitivity
      and specificity. 

PMID- 23862062
TI  - Cerebral vasospasm in traumatic brain injury.
AB  - Vasospasm following traumatic brain injury (TBI) may dramatically affect the
      neurological and functional recovery of a vulnerable patient population. While
      the reported incidence of traumatic vasospasm ranges from 19%-68%, the true
      incidence remains unknown due to variability in protocols for its detection. Only
      3.9%-16.6% of patients exhibit clinical deficits. Compared to vasospasm resulting
      from aneurysmal SAH (aSAH), the onset occurs earlier and the duration is shorter.
      Overall, the clinical course tends to be milder, although extreme cases may
      occur. Traumatic vasospasm can occur in the absence of subarachnoid hemorrhage.
      Surveillance transcranial Doppler ultrasonography (TCD) has been utilized to
      monitor for radiographic vasospasm following TBI. However, effective treatment
      modalities remain limited. Hypertension and hypervolemia, the mainstays of
      treatment of vasospasm associated with aSAH, must be used judiciously in TBI
      patients, and calcium-channel blockers have offered mixed clinical results.
      Currently, the paucity of large prospective cohort studies and level-one data
      limits the ability to form evidence-based recommendations regarding the diagnosis
      and management of vasospasm associated with TBI. 

PMID- 23862063
TI  - Theory of Mind Deficit versus Faulty Procedural Memory in Autism Spectrum
      Disorders.
AB  - Individuals with autism spectrum disorders (ASD) have impairments in social
      interaction, communicative capacity, and behavioral flexibility (core triad).
      Three major cognitive theories (theory of mind deficit, weak central coherence,
      and executive dysfunction) seem to explain many of these impairments. Currently,
      however, the empathizing-systemizing (a newer version of the theory of mind
      deficit account) and mnesic imbalance theories are the only ones that attempt to
      explain all these core triadic symptoms of ASD On the other hand, theory of mind
      deficit in empathizing-systemizing theory is the most influential account for
      ASD, but its counterpart in the mnesic imbalance theory, faulty procedural
      memory, seems to occur earlier in development; consequently, this might be a
      better solution to the problem of the etiology of ASD, if it truly meets the
      precedence criterion. Hence, in the present paper I review the reasoning in favor
      of the theory of mind deficit but with a new interpretation based on the mnesic
      imbalance theory, which posits that faulty procedural memory causes deficits in
      several cognitive skills, resulting in poor performance in theory of mind tasks. 

PMID- 23862064
TI  - Flexibility of older adults aged 55-86 years and the influence of physical
      activity.
AB  - Cross-sectional age-related differences in flexibility of older adults aged 55-86
      years of varying activity levels were examined. Shoulder abduction and hip
      flexion flexibility measurements were obtained from 436 individuals (205 men, 71
      +/- 9 years; 231 women, 72 +/- 8 years). Total physical activity was assessed
      using the Minnesota Leisure-Time Physical Activity Questionnaire. Shoulder
      abduction showed a significant decline averaging 5 degrees/decade in men and 6
      degrees/decade in women. Piecewise linear regression showed an accelerated
      decline in men starting at the age of 71 years of 0.80 degrees/year, whereas in
      women the onset of decline (0.74 degrees/year) was 63 years. Men and women showed
      a significant decline in hip flexion (men: 6 degrees/decade; women: 7
      degrees/decade). Piecewise linear regression revealed a rate of decline of 1.16
      degrees/year beginning at 71 years in men and in women a single linear decline of
      0.66 degrees/year. Multiple regression analysis showed that age and physical
      activity accounted for only 9% of the variance in hip flexion in women and 10% in
      men, with age but not physical activity remaining significant. Similarly for
      shoulder abduction, age was significant but not physical activity, in a model
      that described 8% of the variance for both sexes. 

PMID- 23862065
TI  - Treadmill Exercise Training Modulates Hepatic Cholesterol Metabolism and
      Circulating PCSK9 Concentration in High-Fat-Fed Mice.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel biomarker of LDL
      clearance and a therapeutic target of cardiovascular disease. We examined the
      effects of aerobic exercise training in modulating PCSK9 abundance and hepatic
      sterol regulation in high-fat-fed C57BL/6 mice. Mice (n = 8) were assigned to a
      low-fat (LF), high-fat (HF), or an HF with exercise (HF + EX) group for 8 weeks.
      The HF + EX group was progressively trained 5 days/week on a motorized treadmill.
      The HF + EX group was protected against body weight (BW) gain and diet-induced
      dyslipidemia compared with the HF group. The HF + EX group demonstrated an
      increase in hepatic PCSK9 mRNA (1.9-fold of HF control, P < 0.05) and a reduction
      in plasma PCSK9 (14%) compared with the HF group. Compared with HF mice, HF + EX
      mice demonstrated reduced hepatic cholesterol (14%) and increased (P < 0.05)
      nuclear SREBP2 protein (1.8-fold of HF group) and LDLr mRNA (1.4-fold of HF
      group). Plasma PCSK9 concentrations correlated positively with plasma non-HDL-C
      (P = 0.01, r = 0.84). Results suggest that treadmill exercise reduces non-HDL
      cholesterol and differentially modulates hepatic and blood PCSK9 abundance in HF
      fed C57BL/6 mice. 

PMID- 23862066
TI  - A Pilot Study of Laparoscopic Doppler Ultrasound Probe to Map Arterial Vascular
      Flow within the Neurovascular Bundle during Robot-Assisted Radical Prostatectomy.
AB  - Purpose. To report on the feasibility of a new Laparoscopic Doppler ultrasound
      (LDU) technology to aid in identifying and preserving arterial blood flow within
      the neurovascular bundle (NVB) during robotic prostatectomy (RARP). Materials and
      Methods. Nine patients with normal preoperative potency and scheduled for a
      bilateral nerve-sparing procedure were prospectively enrolled. LDU was used to
      measure arterial flow at 6 anatomic locations alongside the prostate, and signal
      intensity was evaluated by 4 independent reviewers. Measurements were made before
      and after NVB dissection. Modifications in nerve-sparing procedure due to LDU use
      were recorded. Postoperative erectile function was assessed. Fleiss Kappa
      statistic was used to evaluate inter-rater agreement for each of the 12
      measurements. Results. Analysis of Doppler signal intensity showed maintenance of
      flow in 80% of points assessed, a decrease in 16%, and an increase in 4%. Plane
      of NVB dissection was altered in 5 patients (56%) on the left and in 4 patients
      (44%) on the right. There was good inter-rater reliability for the 4 reviewers.
      Use of the probe did not significantly increase operative time or result in any
      complications. Seven (78%) patients had recovery of erections at time of the 8
      month follow-up visit. Conclusions. LDU is a safe, easy to use, and effective
      method to identify local vasculature and anatomic landmarks during RARP, and can
      potentially be used to achieve greater nerve preservation. 

PMID- 23862067
TI  - Molecular Genetic Diversity and Quantitation of Methanogen in Ruminal Fluid of
      Buffalo (Bubalus bubalis) Fed Ration (Wheat Straw and Concentrate Mixture Diet).
AB  - High roughage diet causes more methane emissions; however, the total methanogen
      abundance is not influenced by roughage proportion. Technologies to reduce
      methane emissions are lacking, and development of inhibitors and vaccines that
      mitigate rumen-derived methane by targeting methanogens relies on present
      knowledge of the methanogens. In this work, we have investigated molecular
      diversity of rumen methanogens of Surti buffalo. DNA from rumen fluid was
      extracted, and 16S rRNA encoding genes were amplified using methanogen specific
      primer to generate 16S rDNA clone libraries. Seventy-six clones were randomly
      selected and analysed by RFLP resulting in 21 operational taxonomic units (OTUs).
      BLAST analysis with available sequences in database revealed sequences of 13 OTUs
      (55 clones) showing similarity with Methanomicrobium sp, 3 OTUs (15 clones) with
      Methanobrevibacter sp. The remaining 5 OTUs (6 clones) belonged to uncultured
      archaea. The phylogenetic analysis indicated that methanogenic communities found
      in the library were clustered in the order of Methanomicrobiales (18 OTUs) and
      Methanobacteriales (3 OTUs). The population of Methanomicrobiales,
      Methanobacteriales, and Methanococcales were also observed, accounting for 1.94%,
      0.72%, and 0.47% of total archaea, respectively. 

PMID- 23862068
TI  - Risk factors of lymph edema in breast cancer patients.
AB  - Background. Lymphedema secondary to breast cancer treatment is a common and
      serious problem for disease survivors. The objective of the current study was to
      identify the risk factors of secondary lymphedema after breast carcinoma
      treatment. Materials & Methods. The breast cancer patients who were followed up
      in three centers in Tehran and Mashhad in 2010 were recruited in the study. The
      circumference measurement was used for defining lymphedema. Results. Among 410
      breast cancer patients, 123 cases (30%) developed lymphedema. Variables such as
      low educational level, body mass index (BMI), higher stage of disease, number of
      involved lymph nodes, comorbid diseases, trauma, infection, and the time after
      surgery showed significant correlation with the development of lymphedema. In
      logistic regression analysis, increase of 1 kg/m(2) in BMI (OR = 1.09; 95%  CI
      1.05-1.15), each number increase in lymph node involvement (OR = 1.15; 95%  CI
      1.08-1.21) and the increase of every 1 month after surgery (OR = 1.01; 95%  CI
      1.01-1.02) significantly increased the risk of lymphedema. Conclusion. The
      results of this study demonstrated that preserving a fitted BMI, emphasis on self
      care, and educating preventive activities may have important roles in decreasing
      the lymphedema incidence and improving the patients' quality of life. 

PMID- 23862069
TI  - Robotic assistance enables inexperienced surgeons to perform unicompartmental
      knee arthroplasties on dry bone models with accuracy superior to conventional
      methods.
AB  - Robotic systems have been shown to improve unicompartmental knee arthroplasty
      (UKA) component placement accuracy compared to conventional methods when used by
      experienced surgeons. We aimed to determine whether inexperienced UKA surgeons
      can position components accurately using robotic assistance when compared to
      conventional methods and to demonstrate the effect repetition has on accuracy.
      Sixteen surgeons were randomised to an active constraint robot or conventional
      group performing three UKAs over three weeks. Implanted component positions and
      orientations were compared to planned component positions in six degrees of
      freedom for both femoral and tibial components. Mean procedure time decreased for
      both robot (37.5 mins to 25.7 mins) (P = 0.002) and conventional (33.8 mins to
      21.0 mins) (P = 0.002) groups by attempt three indicating the presence of a
      learning curve; however, neither group demonstrated changes in accuracy. Mean
      compound rotational and translational errors were lower in the robot group
      compared to the conventional group for both components at all attempts for which
      rotational error differences were significant at every attempt. The conventional
      group's positioning remained inaccurate even with repeated attempts although
      procedure time improved. In comparison, by limiting inaccuracies inherent in
      conventional equipment, robotic assistance enabled surgeons to achieve precision
      and accuracy when positioning UKA components irrespective of their experience. 

PMID- 23862070
TI  - Toxic Epidermal Necrolysis and Graft-versus-Host Reaction: Revisiting a Puzzling
      Similarity.
AB  - Drug-induced toxic epidermal necrolysis (TEN) and acute cutaneous graft-versus
      host reaction (GVHR) under immunopreventive therapy share some histopathological
      resemblance. So far, there are no serum biomarkers and no immunohistochemical
      criteria distinguishing with confidence and specificity the skin lesions of TEN
      and GVHR. Both diseases present as an inflammatory cell-poor necrotic reaction of
      the epidermis. This report compares three sets of 15 immunostaining patterns
      found in TEN, GVHR, and partial thickness thermal burns (PTTB), respectively.
      Three series of 17 skin biopsies were scrutinized. Irrespective of the distinct
      causal pathobiology of TEN and GVHR, similar secondary effector cells were
      recruited in lesional skin. Burns were less enriched in cells of the monocyte
      macrophage disease. These cells likely exert deleterious effects in TEN and GVHR
      and cannot be simply regarded as passive bystanders. These life-threatening
      conditions are probably nursed, at least in part, by macrophages. 

PMID- 23862071
TI  - Human Serum PCSK9 Is Elevated at Parturition in Comparison to Nonpregnant
      Subjects While Serum PCSK9 from Umbilical Cord Blood is Lower Compared to
      Maternal Blood.
AB  - Background. Serum lipids including total cholesterol (TC), triglycerides (TG),
      and low density lipoprotein cholesterol (LDL-C) are increased in pregnancy. Serum
      proprotein convertase subtilisin kexin 9 (PCSK9) is a significant player in
      lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the
      surface of the liver, inhibiting clearance of LDL-C. Therefore, our study
      assessed serum PCSK9 concentrations at parturition (Maternal) compared to a
      nonpregnant (Control) cohort, as well as between mother and newborn (Maternal and
      Newborn). Methods. Blood was collected from women at parturition and from
      umbilical cords. Serum lipids and PCSK9 were measured and data were analysed for
      significance by Mann-Whitney U test at P < 0.05 and presented as median levels.
      Spearman's correlations were made at a 95% confidence interval. Results. Serum
      PCSK9 was significantly higher in Maternal versus Control cohorts (493.1 versus
      289.7 ng/mL; P < 0.001, resp.), while the Newborn cohort was significantly lower
      than Maternal (278.2 versus 493.1 ng/mL; P < 0.0001, resp.). PCSK9 was
      significantly correlated with TC and HDL-C in Maternal and with TC, LDL-C, and
      HDL-C in Newborn cohorts. Conclusions. Our study provides the first quantitative
      report on PCSK9 in pregnancy (at parturition) and in umbilical cord blood.
      Further research will determine how these changes may affect lipoprotein levels
      during this physiological state. 

PMID- 23862072
TI  - Somatosensory and pharyngolaryngeal auras in temporal lobe epilepsy surgeries.
AB  - Purpose. Somatosensory (SSA) and pharyngolaryngeal auras (PLA) may suggest an
      extratemporal onset (e.g., insula, second somatosensory area). We sought to
      determine the prognostic significance of SSA and PLA in temporal lobe epilepsy
      (TLE) patients undergoing epilepsy surgery. Methods. Retrospective review of all
      patients operated for refractory TLE at our institution between January 1980 and
      July 2007 comparing outcome between patients with SSA/PLA to those without.
      Results. 158 patients underwent surgery for pharmacoresistant TLE in our
      institution. Eleven (7%) experienced SSA/PLA as part of their seizures. All but
      one had lesional (including hippocampal atrophy/sclerosis) TLE. Compared to
      patients without SSA or PLA, these patients were older (P = 0.049), had a higher
      prevalence of early ictal motor symptoms (P = 0.022) and prior CNS infection (P =
      0.022), and were less likely to have a localizing SPECT study (P = 0.025). A
      favorable outcome was achieved in 81.8% of patients with SSA and/or PLA and 90.4%
      of those without SSA or PLA (P > 0.05). Conclusion. Most patients with
      pharmacoresistant lesional TLE appear to have a favorable outcome following
      temporal lobectomy, even in the presence of SSA and PLA. 

PMID- 23862073
TI  - Left-to-Right Shunt with Congenital Heart Disease: Single Center Experience.
AB  - Objective. The objective of this study was to determine the frequency of
      pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) with an
      isolated, large left-to-right shunt and to indicate the factors in the
      development of PAH. Methods. The pressure measurements in the cardiac chambers
      and the calculations based on the Fick's principle were compared among 3 separate
      groups of patients, respectively, with PAH, with hyperkinetic pulmonary
      hypertension (HPH), and with neither PAH nor HPH. Results. PAH was diagnosed in
      30 (12.3%) patients, HPH in 35 (14.4%), while 177 (73.1%) were free of either.
      The highest risk for the development of PAH was found in the presence of
      perimembranous ventricular septal defect. A statistically significant difference
      was seen among these groups as to their left atrial pressure (p = 0.005) and the
      mean pulmonary arterial pressure (PAPmean; p < 0.001). While a correlation was
      present between RpI on one hand and age on the other (p = 0.014), a multiple
      linear regression could not evidence any correlation among age (p = 0.321),
      gender (p = 0.929). Conclusion. Our findings do not allow establishing a
      correlation between the duration of the high pulmonary flow and pulmonary
      vascular resistance increase or PAH development in isolated left-to-right shunts
      with congenital heart diseases. 

PMID- 23862074
TI  - Risk factors for coronary drug-eluting stent thrombosis: influence of procedural,
      patient, lesion, and stent related factors and dual antiplatelet therapy.
AB  - The complication of stent thrombosis (ST) emerged at a rate of 0.5% annually for
      first-generation drug-eluting stents (DES), often presenting as death or
      myocardial infarction. Procedural factors such as stent underexpansion and
      malapposition are risk factors for ST in patients. The type of lesion being
      treated and lesion morphology also influence healing after treatment with DES and
      can contribute to ST. Second-generation DES such as the XIENCE V everolimus
      eluting stent differ from the first-generation stents with respect to
      antiproliferative agents, coating technologies, and stent frame. Improvements in
      stent structure have resulted in a more complete endothelialization, thereby
      decreasing the incidence of ST. Bioresorbable scaffolds show promise for
      restoring vasomotor function and minimizing rates of very late ST. Post-PCI
      treatment with aspirin and clopidogrel for a year is currently the standard of
      care for DES, but high-risk patients may benefit from more potent antiplatelet
      agents. The optimal duration of DAPT for DES is currently unclear and will be
      addressed in large-scale randomized clinical trials. 

PMID- 23862075
TI  - Altered functional connectivity of cognitive-related cerebellar subregions in
      well-recovered stroke patients.
AB  - The cerebellum contains several cognitive-related subregions that are involved in
      different functional networks. The cerebellar crus II is correlated with the
      frontoparietal network (FPN), whereas the cerebellar IX is associated with the
      default-mode network (DMN). These two networks are anticorrelated and
      cooperatively implicated in cognitive control, which may facilitate the motor
      recovery in stroke patients. In the present study, we aimed to investigate the
      resting-state functional connectivity (rsFC) changes in 25 subcortical ischemic
      stroke patients with well-recovered global motor function. Consistent with
      previous studies, the crus II was correlated with the FPN, including the
      dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex, and the
      cerebellar IX was correlated with the DMN, including the posterior cingulate
      cortex/precuneus (PCC/Pcu), medial prefrontal cortex (MPFC), DLPFC, lateral
      parietal cortices, and anterior temporal cortices. No significantly increased
      rsFCs of these cerebellar subregions were found in stroke patients, suggesting
      that the rsFCs of the cognitive-related cerebellar subregions are not the
      critical factors contributing to the recovery of motor function in stroke
      patients. The finding of the disconnection in the cerebellar-related cognitive
      control networks may possibly explain the deficits in cognitive control function
      even in stroke patients with well-recovered global motor function. 

PMID- 23862077
TI  - Stability of betaine capsules.
AB  - Betaine is used to treat homocystinuria and is not available in Canada as a
      formulated drug. In order to facilitate the administration of this compound to
      patients, a capsule formulation and an evaluation of its stability were required.
      Capsule formulations of betaine were developed (160 mg and 625 mg of betaine per
      capsule). As betaine has no chromophore, an HPLC-ELSD analytical method was also
      developed. The critical quality attributes of these formulations were evaluated
      (content assay, content uniformity, and dissolution) as well as their stability.
      Capsules with acceptable quality attributes were produced. These capsules
      remained stable for 1 year when stored in airtight containers at controlled room
      temperature. However, shelf life decreased dramatically in nonairtight containers
      at 30 degrees C (3 months for the lactose-containing capsules of 160 mg and 6
      months for the capsules of 625 mg). 

PMID- 23862078
TI  - Myocardial dysfunction in acute traumatic brain injury relieved by surgical
      decompression.
AB  - Traumatic brain injury (TBI) is a major public health issue and is a leading
      cause of death in North America. After a primary TBI, secondary brain insults can
      predispose patients to a worse outcome. One of the earliest secondary insults
      encountered during the perioperative period is hypotension, which has been
      directly linked to both mortality and poor disposition after TBI. Despite this,
      it has been shown that hypotension commonly occurs during surgery for TBI. We
      present a case of intraoperative hypotension during surgery for TBI, where the
      use of transthoracic echocardiography had significant diagnostic and therapeutic
      implications for the management of our patient. We then discuss the issue of
      cardiac dysfunction after brain injury and the implications that echocardiography
      may have in the management of this vulnerable patient population. 

PMID- 23862079
TI  - Papilliferous keratoameloblastoma: an extremely rare case report.
AB  - Odontogenic tumors develop in the jaw bones from the odontogenic tissue-oral
      epithelium in tooth germ, enamel organ, dental papilla, reduced enamel
      epithelium, remnants of Hertwig's root sheath or dental lamina, and so forth.
      Hence, a bewildering variety of tumors are encountered in the maxilla and
      mandible. Ameloblastoma is the second most common odontogenic neoplasm after
      odontomes, and it has numerous clinical and histologic variants. We report a very
      rare histologic variant: the papilliferous keratoameloblastoma which is the fifth
      reported case in the English literature. 

PMID- 23862080
TI  - Diabetic myonecrosis: an atypical presentation.
AB  - Diabetic myonecrosis is a frequently unrecognized complication of longstanding
      and poorly controlled diabetes mellitus. The clinical presentation is swelling,
      pain, and tenderness of the involved muscle, most commonly the thigh muscles.
      Management consists of conservative measures including analgesia and rest. Short
      term prognosis is good, but long-term prognosis is poor with most patients dying
      within 5 years. Failure to properly identify this condition will expose the
      patient to aggressive measures that could result in increased morbidity. To our
      knowledge this is the first case reported in which there was involvement of
      multiple muscle groups including upper and lower limbs. 

PMID- 23862081
TI  - Klippel-Trenaunay Syndrome Causing Life-Threatening GI Bleeding: A Case Report
      and Review of the Literature.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare congenital syndrome of vascular
      malformations and soft tissue and bone hypertrophy. Vascular malformations can
      affect multiple organ systems. Involvement of the gastrointestinal (GI) tract is
      uncommon in KTS, but it can be a source of life-threatening bleeding. We report a
      case of a 32-year-old male with a known diagnosis of KTS who presented with a
      life-threatening rectal bleeding and was treated with proctosigmoidectomy and
      massive blood products transfusion. He expired after a long hospitalization. We
      then review the literature on KTS and management of some of its complications. 

PMID- 23862082
TI  - Legionellosis and lung abscesses: contribution of legionella quantitative real
      time PCR to an adapted followup.
AB  - We report a case of severe Legionnaires' disease (LD) complicated by a lung
      abscess in an immunocompetent patient who required ECMO therapy and thoracic
      surgery. The results of repeated Legionella quantitative real-time PCR performed
      on both sera and respiratory samples correlated with the LD severity and the poor
      clinical outcome. Moreover, the PCR allowed for the detection of Legionella DNA
      in the lung abscess specimen, which was negative when cultured for Legionella.
      This case report provides a logical basis for further investigations to examine
      whether the Legionella quantitative PCR could improve the assessment of LD
      severity and constitute a prognostic marker. 

PMID- 23862083
TI  - An unusual metastasis of a transglottic squamous cell carcinoma to the forearm.
AB  - Introduction. Each year around 2,200 people in the UK are diagnosed with
      laryngeal SCC (Office of National Statistics 2009). Compared to pharyngeal
      carcinoma, it is a highly curable disease with a survival rate of around 60% for
      all stages and all forms of treatment. Case Presentation. We present the case of
      a 60-year-old man with a previously treated T4 N2c transglottic squamous cell
      carcinoma (SCC), who developed an isolated swelling in the extensor compartment
      of his right forearm at 6 months after radical laryngectomy with bilateral neck
      dissection. Fine needle aspiration of the forearm lesion revealed SCC consistent
      with a metastasis from the laryngeal primary. MRI revealed that the lesion was
      confined to the muscle. Initial staging CT showed no distant metastases or signs
      of advanced disease, including no evidence of axillary nodal involvement.
      Conclusion. This case is therefore unusual, as one of only 2 cases reported in
      the scientific literature of isolated distant muscular metastasis from a
      laryngeal squamous cell carcinoma. We conclude that any muscular swelling, in the
      setting of previous head and neck malignancy, should be treated with a high
      degree of suspicion for metastasis and investigated promptly. 

PMID- 23862076
TI  - Neural plasticity and proliferation in the generation of antidepressant effects:
      hippocampal implication.
AB  - It is widely accepted that changes underlying depression and antidepressant-like
      effects involve not only alterations in the levels of neurotransmitters as
      monoamines and their receptors in the brain, but also structural and functional
      changes far beyond. During the last two decades, emerging theories are providing
      new explanations about the neurobiology of depression and the mechanism of action
      of antidepressant strategies based on cellular changes at the CNS level. The
      neurotrophic/plasticity hypothesis of depression, proposed more than a decade
      ago, is now supported by multiple basic and clinical studies focused on the role
      of intracellular-signalling cascades that govern neural proliferation and
      plasticity. Herein, we review the state-of-the-art of the changes in these
      signalling pathways which appear to underlie both depressive disorders and
      antidepressant actions. We will especially focus on the hippocampal cellularity
      and plasticity modulation by serotonin, trophic factors as brain-derived
      neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) through
      intracellular signalling pathways-cAMP, Wnt/ beta -catenin, and mTOR. Connecting
      the classic monoaminergic hypothesis with proliferation/neuroplasticity-related
      evidence is an appealing and comprehensive attempt for improving our knowledge
      about the neurobiological events leading to depression and associated to
      antidepressant therapies. 

PMID- 23862084
TI  - Primary immature teratoma of the uterus relapsing as malignant neuroepithelioma:
      case report and review of the literature.
AB  - Background. Although some mature cases of teratomas have recently been described
      in the cervix, they are not commonly found in the uterus, especially in immature
      forms. An immature uterine teratoma relapsing after surgery as malignant
      neuroepithelioma has never been reported in the literature. Case Presentation. We
      describe a case of immature teratoma which occurred primarily in the uterus in a
      56-year-old female. Treatment consisted of total simple hysterectomy. Three
      months after surgery, the patient relapsed with voluminous pelvic mass and was
      treated with bleomycin, etoposide, and cisplatin-containing chemotherapy regimen.
      Conclusion. In this report and according to the pertinent literature, clinical
      and pathological features and management of uterine immature teratomas are
      discussed. The mainstay of treatment is surgery. The prognosis of this unusual
      disease remains uncertain. 

PMID- 23862085
TI  - An unusual case of hand xanthomatosis.
AB  - Tendon xanthomatosis often accompanies familial hypercholesterolaemia, but it can
      also occur in other pathologic states. Of the musculoskeletal system, the
      Achilles tendon is the most commonly effected tendon due to xanthomatosis.
      Although there are previous reports for flexor tendon involvement, to our
      knowledge there is no report in the English literature about bilateral hand
      extensor tendon xanthomatosis that causes restriction in the range of motion. The
      case that will be presented in this report is therefore unique. 

PMID- 23862086
TI  - Lingual Haematoma due to Tenecteplase in a Patient with Acute Myocardial
      Infarction.
AB  - The use of intravenous thrombolytic agents has revolutionised the treatment of
      acute myocardial infarction. However, the improvement in mortality rate achieved
      with these drugs is tempered by the risk of serious bleeding complications,
      including intracranial haemorrhage. Tenecteplase is a genetically engineered
      mutant tissue plasminogen activator. Haemorrhagic complications of tissue
      plasminogen activator (tPA) are well known. Compared to other tPAs, tenecteplase
      use leads to lower rates of bleeding complications. Here, we report a case of
      unusual site of spontaneous bleeding, intralingual haematoma during tenecteplase
      therapy following acute myocardial infarction, which caused significant upper
      airway obstruction and required tracheotomy to maintain the patient's airway.
      Clinical dilemmas related to securing the airway or reversing the effects of
      tissue plasminogen activator are discussed. 

PMID- 23862087
TI  - A case report of malignant melanoma of the sphenoid sinus.
AB  - Malignant melanoma of the sphenoid sinus is a very rare disease, and only 6 cases
      have previously been reported. The present case involved a 74-year-old woman who
      was examined for visual disturbance of the left eye. Computed tomography revealed
      a soft tissue shadow, but only mucosal hypertrophy was found on opening the
      sphenoid sinus under general anesthesia. One month postoperatively, visual
      disturbance of the right eye and paresis of cranial nerve III appeared. Malignant
      melanoma was diagnosed from biopsy. Multiple bone metastases were identified, but
      the patient declined active treatment. As a result, palliative care was provided
      and she died 3 months later. When there is no improvement in postoperative visual
      acuity as in this case, in consideration of the possibility of neoplastic
      lesions, rigorous followup including monitoring for neurological symptoms is
      warranted. 

PMID- 23862088
TI  - Unilateral Intraparotid Swelling: A Case Report of Kimura's Disease and Review of
      Differential Diagnosis.
AB  - An interesting case of Kimura's disease was described in the 42-year-old patient
      manifesting itself as a unilateral parotid swelling, albeit the disease usually
      affects both parotid glands. Furthermore, first pathohistological finding was not
      suggestive of the disease, revealing only fatty tissue, but on the repeated
      biopsy together with CT the correct diagnosis was established. It should be
      emphasized that Kimura's disease has to be taken into account while making
      differential diagnosis in parotid gland swellings, especially in people of
      Oriental origin. 

PMID- 23862089
TI  - Retropharyngeal calcific tendinitis mimicking a retropharyngeal phlegmon.
AB  - Background. Acute retropharyngeal tendinitis is a little known but not an
      uncommon condition. It was first described by Hartley in 1964 as an inflammation
      of the longus colli muscle secondary to calcium crystals deposition on its
      insertion. The calcifications are mostly located on the oblique portion of the
      muscle at the level of C1-C2. Methods. We will describe this disease through 4
      cases that presented in our institution. Results. The most common symptoms are
      severe neck pain, odynophagia, and a painful restriction of neck movement. It is
      associated with mild fever and inflammatory lab findings such as a slight
      elevation of white blood cell count, erythrocyte sedimentation rate, and C
      reactive protein. CT scan is recommended as the first-line imaging modality to
      establish a diagnosis. Treatments consist of NSAIDs and analgesics to accelerate
      the healing process. If symptoms are severe, a course of corticosteroids is
      required. Conclusion. Since the clinical and laboratory findings of this
      condition and those of a retropharyngeal abscess overlap, it is important to
      establish the right diagnosis in order to prevent more invasive procedures. A
      good knowledge of this clinical entity by otolaryngologists would prevent delays
      in hospital discharge and unnecessary anxiety. 

PMID- 23862090
TI  - A unique case of pneumatised styloid process with cholesteatoma.
AB  - Pneumatisation of styloid process is a very rare finding and has never been
      reported previously. We present a unique case of a pneumatised styloid process
      with a cholesteatoma arising within the cavity. We describe the clinical
      features, associated radiological findings, and management of this lesion. 

PMID- 23862091
TI  - Pediatric Cryptococcal Lymphadenitis in the Absence of AIDS: Case Report and
      Literature Review.
AB  - We present a rare case of cryptococcal lymphadenitis without immunocompromization
      in a two-and-a-half-year-old child. He was referred to our center with a fifteen
      day history of continued fever. Ultrasound and computed tomography (CT) revealed
      the enlargement of multiple lymph nodes and lung reticulonodular shadows.
      Hematological, immunological, and microbiological tests for hepatitis, lymphoma,
      AIDS, and immunoglobulin deficiencies were negative. Laboratory tests
      demonstrated elevated erythrocyte sedimentation rate, elevated plasma and urinary
      beta2-microglobulin (beta2-MG) levels, and elevated C-reactive protein and
      fibrinogen. Both blood routine and bone marrow aspiration showed elevated
      eosinophil granulocytes. The diagnosis of cryptococcal lymphadenitis was obtained
      by excisional biopsy of the cervical lymph nodes. The patient was treated with
      intravenous amphotericin B and oral flucytosine for five weeks, then with
      subsequent oral fluconazole for three months. The patient is now doing well. Our
      case suggests that the diagnosis of cryptococcal lymphadenitis is very difficult
      without etiology and pathology, especially for a patient with a normal immune
      system; lymph node biopsy is necessary to diagnose it, and immediate antifungal
      treatment is necessary to treat it. 

PMID- 23862092
TI  - Relapsing Campylobacter jejuni Systemic Infections in a Child with X-Linked
      Agammaglobulinemia.
AB  - X-linked agammaglobulinemia (XLA) is a primary immunodeficiency of the humoral
      compartment, due to a mutation in the Bruton tyrosine kinase (BTK) gene,
      characterized by a severe defect of circulating B cells and serum
      immunoglobulins. Recurrent infections are the main clinical manifestations;
      although they are especially due to encapsulated bacteria, a specific association
      with Campylobacter species has been reported. Here, we report the case of a boy
      with XLA who presented with relapsing Campylobacter jejuni systemic infections.
      His clinical history supports the hypothesis of the persistence of C. jejuni in
      his intestinal tract. Indeed, as previously reported, XLA patients may become
      chronic intestinal carriers of Campylobacter, even in absence of symptoms, with
      an increased risk of relapsing bacteraemia. The humoral defect is considered to
      be crucial for this phenomenon, as well as the difficulties to eradicate the
      pathogen with an appropriate antibiotic therapy; drug resistance is raising in
      Campylobacter species, and the appropriate duration of treatment has not been
      established. C. jejuni should always be suspected in XLA patients with signs and
      symptoms of systemic infection, and treatment should be based on antibiogram to
      assure the eradication of the pathogen. 

PMID- 23862093
TI  - Drain-site hernia containing the vermiform appendix: report of a case.
AB  - The herniated vermiform appendix has been described as content of every hernia
      orifice in the right lower quadrant. While the femoral and inguinal herniated
      vermiform appendix is frequent enough to result in an own designation, port-site
      or even drain-site hernias are less frequently described. We report the case of a
      62-year-old woman who presented with right lower quadrant pain seven years after
      Roux-en-Y Cystojejunostomy for a pancreatic cyst. CT scan showed herniation of
      the vermiform appendix through a former drain-site. A diagnostic laparoscopy with
      appendectomy and direct closure of the abdominal wall defect combined with mesh
      reinforcement was performed. Despite the decreasing use of intraperitoneal drains
      over the recent years, a multitude of patients had intraperitoneal drainage in
      former times. These patients face nowadays the risk of drain-site hernias with
      sometimes even unexpected structures inside. 

PMID- 23862094
TI  - Endovascular treatment of isolated iliac artery aneurysms with anaconda stent
      graft limb.
AB  - Isolated aneurysms of the iliac arteries are relatively rare conditions that
      traditionally have been treated by surgical reconstruction. We report our
      experience with endovascular treatment of iliac artery aneurysms (IAAs) with
      Anaconda stent graft limb. Two male patients were found to have 4.5 and 3.6 cm
      isolated common IAAs, respectively. The endograft was successfully advanced and
      deployed precisely to the intended position in both cases. In one case the
      internal iliac artery was embolized. No type I or II endoleak was observed
      immediately after the procedure. In one patient postimplantation fever (>38
      degrees C) and gluteal claudication occurred. After 2 years followup both iliac
      endovascular stent grafts are patent and without endoleak. Endovascular treatment
      with Anaconda limb stent graft seems to be a safe and feasible alternative to
      open surgery. 

PMID- 23862095
TI  - Dropouts and compliance in exercise interventions targeting bone mineral density
      in adults: a meta-analysis of randomized controlled trials.
AB  - Background. Dropouts and compliance to exercise interventions targeting bone
      mineral density (BMD) in adults are not well established. The purpose of this
      study was to address that gap. Methods. Meta-analysis of randomized controlled
      exercise intervention trials in adults >=18 years of age. The primary outcomes
      were dropouts in the exercise and control groups as well as compliance to the
      exercise interventions. A random-effects model was used to pool results.
      Moderator analyses were conducted using mixed-effects ANOVA-like models and
      metaregression. Statistical significance was set at P <= 0.05. Results. Thirty
      six studies representing 3,297 participants (1,855 exercise, 1,442 control) were
      included. Dropout rates in the exercise and control groups averaged 20.9% (95% CI
      16.7%-25.9%) and 15.9% (11.8%-21.1%) while compliance to exercise was 76.3%
      (71.7%-80.3%). For both exercise and control groups, greater dropout rates were
      associated with studies conducted in the USA versus other countries, females
      versus males, premenopausal versus postmenopausal women, younger versus older
      participants, longer studies (controls only), and high- versus moderate-intensity
      training (exercisers only). Greater compliance to exercise was associated with
      being female, home- or facility-based exercise versus both, and shorter studies.
      Conclusion. These findings provide important information for researchers and
      practitioners with respect to exercise programs targeting BMD in adults. 

PMID- 23862096
TI  - Bovine tuberculosis and brucellosis in traditionally managed livestock in
      selected districts of southern province of zambia.
AB  - A study was performed in 2008 to estimate the prevalence of tuberculosis and
      brucellosis in traditionally reared cattle of Southern Province in Zambia in four
      districts. The single comparative intradermal tuberculin test (SCITT) was used to
      identify TB reactors, and the Rose Bengal test (RBT), followed by confirmation
      with competitive enzyme-linked immunosorbent assay (c-ELISA), was used to test
      for brucellosis. A total of 459 animals were tested for tuberculosis and 395 for
      brucellosis. The overall prevalence of BTB based on the 4 mm and 3 mm cutoff
      criteria was 4.8% (95% CI: 2.6-7.0%) and 6.3% (95% CI: 3.8-8.8%), respectively.
      Change in skin thickness on SCITT was influenced by initial skin-fold thickness
      at the inoculation site, where animals with thinner skin had a tendency to give a
      larger tuberculin response. Brucellosis seroprevalence was estimated at 20.7%
      (95% CI: 17.0-24.4%). Comparison between results from RBT and c-ELISA showed good
      agreement (84.1%) and revealed subjectivity in RBT test results. Differences in
      brucellosis and tuberculosis prevalence across districts were attributed to type
      of husbandry practices and ecological factors. High prevalence of tuberculosis
      and brucellosis suggests that control programmes are necessary for improved
      cattle productivity and reduced public health risk. 

PMID- 23862098
TI  - The development of hematopoietic and mesenchymal stem cell transplantation as an
      effective treatment for multiple sclerosis.
AB  - This article examines the current use and future implications of stem cell
      therapy in treating Multiple Sclerosis (MS). MS is the most common neurological
      disease in young adults, affecting approximately two million people worldwide.
      Currently there is no cure for MS. The standard treatment of MS involves disease
      modifying drugs, which work to alleviate the symptoms of MS. However, these drugs
      carry adverse side effects and are ineffective in preventing disease progression
      in many MS patients. Hematopoietic stem cell transplantation (HSCT) was first
      used in 1995 to treat patients with severe rapidly progressing MS. The HSCT
      treatment protocol has evolved into a less intense conditioning regimen that is
      currently demonstrating efficacy in treating patients with variable disease
      severity-with best results in early-stage rapidly progressing MS patients with
      active CNS inflammation. Mesenchymal stem cell therapy (MSCT) is an experimental
      stem cell therapy currently undergoing clinical trials. Animal models and early
      clinical trials have shown promise that MSCT might be a low risk treatment to
      precipitate neuroregeneration and immunomodulation in MS patients. Specifically,
      neuroprogenitor and placental-derived mesenchymal stem cells offer the best hope
      for a practical treatment for MS. Stem cell therapy, and perhaps a combinatorial
      therapeutic approach, holds promise for a better treatment for MS. 

PMID- 23862099
TI  - Amniotic fluid derived stem cells give rise to neuron-like cells without a
      further differentiation potential into retina-like cells.
AB  - Amniotic fluid contains heterogeneous cell types and has become an interesting
      source for obtaining fetal stem cells. These stem cells have a high proliferative
      capacity and a good differentiation potential and may thus be suitable for
      regenerative medicine. As there is increasing evidence, that these stem cells are
      also able to be directed into the neural lineage, in our study we investigated
      the neuronal and glial differentiation potential of these cells, so that they may
      also be applied to cure degenerative diseases of the retina. Mesenchymal stem
      cells were isolated from routine prenatal amniocentesis at 15 to 18 weeks of
      pregnancy of human amniotic fluid and expanded in the cell culture. Cells were
      cultivated according to standard procedures for mesenchymal stem cells and were
      differentiated along the neural lineage using various protocols. Furthermore, it
      was also tried to direct them into cell types of the retina as well as into
      endothelial cells. Cells of more than 72 amniotic fluid samples were collected
      and characterized. While after induction neural-like phenotypes could actually be
      detected, which was confirmed using neural marker proteins such as GFAP and
      betaIII tubulina further differentiation into retinal like cells could not
      reliably be shown. These data suggest that amniotic fluid derived cells are an
      interesting cell source, which may also give rise to neural-like cells. However,
      a more specific differentiation into neuronal and glial cells could not
      unequivocally be shown, so that further investigations have to becarried out. 

PMID- 23862097
TI  - On becoming neural: what the embryo can tell us about differentiating neural stem
      cells.
AB  - THE EARLIEST STEPS OF EMBRYONIC NEURAL DEVELOPMENT ARE ORCHESTRATED BY SETS OF
      TRANSCRIPTION FACTORS THAT CONTROL AT LEAST THREE PROCESSES: the maintenance of
      proliferative, pluripotent precursors that expand the neural ectoderm; their
      transition to neurally committed stem cells comprising the neural plate; and the
      onset of differentiation of neural progenitors. The transition from one step to
      the next requires the sequential activation of each gene set and then its down
      regulation at the correct developmental times. Herein, we review how these gene
      sets interact in a transcriptional network to regulate these early steps in
      neural development. A key gene in this regulatory network is FoxD4L1, a member of
      the forkhead box (Fox) family of transcription factors. Knock-down experiments in
      Xenopus embryos show that FoxD4L1 is required for the expression of the other
      neural transcription factors, whereas increased FoxD4L1 levels have three
      different effects on these genes: up-regulation of neural ectoderm precursor
      genes; transient down-regulation of neural plate stem cell genes; and down
      regulation of neural progenitor differentiation genes. These different effects
      indicate that FoxD4L1 maintains neural ectodermal precursors in an immature,
      proliferative state, and counteracts premature neural stem cell and neural
      progenitor differentiation. Because it both up-regulates and down-regulates
      genes, we characterized the regions of the FoxD4L1 protein that are specifically
      involved in these transcriptional functions. We identified a transcriptional
      activation domain in the N-terminus and at least two domains in the C-terminus
      that are required for transcriptional repression. These functional domains are
      highly conserved in the mouse and human homologues. Preliminary studies of the
      related FoxD4 gene in cultured mouse embryonic stem cells indicate that it has a
      similar role in promoting immature neural ectodermal precursors and delaying
      neural progenitor differentiation. These studies in Xenopus embryos and mouse
      embryonic stem cells indicate that FoxD4L1/FoxD4 has the important function of
      regulating the balance between the genes that expand neural ectodermal precursors
      and those that promote neural stem/progenitor differentiation. Thus, regulating
      the level of expression of FoxD4 may be important in stem cell protocols designed
      to create immature neural cells for therapeutic uses. 

PMID- 23862100
TI  - A robust method to derive functional neural crest cells from human pluripotent
      stem cells.
AB  - Neural crest (NC) cells contribute to the development of many complex tissues of
      all three germ layers during embryogenesis, and its abnormal development accounts
      for several congenital birth defects. Generating NC cells-including specific
      subpopulations such as cranial, cardiac, and trunk NC cells-from human
      pluripotent stem cells will provide a valuable model system to study human
      development and disease. Here, we describe a rapid and robust NC differentiation
      method called "LSB-short" that is based on dual SMAD pathway inhibition. This
      protocol yields high percentages of NC cell populations from multiple human
      induced pluripotent stem and human embryonic stem cell lines in 8 days. The
      resulting cells can be propagated easily, retain NC marker expression over
      multiple passages, and can spontaneously differentiate into several NC-derived
      cell lineages, including smooth muscle cells, peripheral neurons, and Schwann
      cells. NC cells generated by this method represent cranial, cardiac and trunk NC
      subpopulations based on global gene expression analyses, are similar to in vivo
      analogues, and express a common set of NC alternative isoforms. Functionally,
      they are also able to migrate appropriately in response to chemoattractants such
      as SDF-1, FGF8b, and Wnt3a. By yielding NC cells that likely represent all NC
      subpopulations in a shorter time frame than other published methods, our LSB
      short method provides an ideal model system for further studies of human NC
      development and disease. 

PMID- 23862101
TI  - Pancytopenia related to dental adhesive in a young patient.
AB  - Copper deficiency resulting in hypocupremia is a rare cause of pancytopenia
      associated with a neurological syndrome. Hypocupremia may also occur as a
      consequence of excessive oral zinc consumption as described by Brewer et al and
      several other groups. Dental fixatives have been described as a potential source
      of hyperzincemia in patients. Despite the recently modified dental fixatives with
      safer zinc content, zinc poisoning results in hypocupremia secondary to
      inappropriate use of them can still happen and more likely be misdiagnosed. We
      describe a case of a patient with pancytopenia who was diagnosed with severe
      aplastic anemia and hypocellular myelodysplastic syndrome and was referred to us
      for consideration of bone marrow transplantation. 

PMID- 23862102
TI  - Local and latitudinal variation in abundance: the mechanisms shaping the
      distribution of an ecosystem engineer.
AB  - Ecological processes that determine the abundance of species within ecological
      communities vary across space and time. These scale-dependent processes are
      especially important when they affect key members of a community, such as
      ecosystem engineers that create shelter and food resources for other species.
      Yet, few studies have examined the suite of processes that shape the abundance of
      ecosystem engineers. Here, we evaluated the relative influence of temporal
      variation, local processes, and latitude on the abundance of an engineering
      insect-a rosette-galling midge, Rhopalomyia solidaginis (Diptera: Cecidomyiidae).
      Over a period of 3-5 years, we studied the density and size of galls across a
      suite of local experiments that manipulated genetic variation, soil nutrient
      availability, and the removal of other insects from the host plant, Solidago
      altissima (tall goldenrod). We also surveyed gall density within a single growing
      season across a 2,300 km latitudinal transect of goldenrod populations in the
      eastern United States. At the local scale, we found that host-plant genotypic
      variation was the best predictor of rosette gall density and size within a single
      year. We found that the removal of other insect herbivores resulted in an
      increase in gall density and size. The amendment of soil nutrients for four years
      had no effect on gall density, but galls were smaller in carbon-added plots
      compared to control and nitrogen additions. Finally, we observed that gall
      density varied several fold across years. At the biogeographic scale, we observed
      that the density of rosette gallers peaked at mid-latitudes. Using meta-analytic
      approaches, we found that the effect size of time, followed by host-plant genetic
      variation and latitude were the best predictors of gall density. Taken together,
      our study provides a unique comparison of multiple factors across different
      spatial and temporal scales that govern engineering insect herbivore density. 

PMID- 23862103
TI  - Looking at microbial metabolism by high-resolution (2)H-NMR spectroscopy.
AB  - We analyzed the applicability of high-resolution (2)H-HMR spectroscopy for the
      analysis of microbe metabolism in samples of mitochondrion isolated from rat
      liver and from aqueous extracts of homogenates of rat liver and other organs and
      tissues in the presence of high D2O contents. Such analysis is possible due to
      the fast microbe adaptation to life in the heavy water. It is also shown that
      some enzymatic processes typical for the intact cells are preserved in the
      homogenized tissue preparations. The microbial and cellular metabolic processes
      can be differentiated via the strategic use of cell poisons and antibiotics. 

PMID- 23862104
TI  - Affect-focused psychodynamic psychotherapy for depression and anxiety through the
      Internet: a randomized controlled trial.
AB  - Background. Psychodynamic psychotherapy is a psychological treatment approach
      that has a growing empirical base. Research has indicated an association between
      therapist-facilitated affective experience and outcome in psychodynamic therapy.
      Affect-phobia therapy (APT), as outlined by McCullough et al., is a psychodynamic
      treatment that emphasizes a strong focus on expression and experience of affect.
      This model has neither been evaluated for depression nor anxiety disorders in a
      randomized controlled trial. While Internet-delivered psychodynamic treatments
      for depression and generalized anxiety disorder exist, they have not been based
      on APT. The aim of this randomized controlled trial was to investigate the
      efficacy of an Internet-based, psychodynamic, guided self-help treatment based on
      APT for depression and anxiety disorders. Methods. One hundred participants with
      diagnoses of mood and anxiety disorders participated in a randomized (1:1 ratio)
      controlled trial of an active group versus a control condition. The treatment
      group received a 10-week, psychodynamic, guided self-help treatment based on APT
      that was delivered through the Internet. The treatment consisted of eight text
      based treatment modules and included therapist contact (9.5 min per client and
      week, on average) in a secure online environment. Participants in the control
      group also received online therapist support and clinical monitoring of symptoms,
      but received no treatment modules. Outcome measures were the 9-item Patient
      Health Questionnaire Depression Scale (PHQ-9) and the 7-item Generalized Anxiety
      Disorder Scale (GAD-7). Process measures were also included. All measures were
      administered weekly during the treatment period and at a 7-month follow-up.
      Results. Mixed models analyses using the full intention-to-treat sample revealed
      significant interaction effects of group and time on all outcome measures, when
      comparing treatment to the control group. A large between-group effect size of
      Cohen's d = 0.77 (95% CI: 0.37-1.18) was found on the PHQ-9 and a moderately
      large between-group effect size d = 0.48 (95% CI: 0.08-0.87) was found on the GAD
      7. The number of patients who recovered (had no diagnoses of depression and
      anxiety, and had less than 10 on both the PHQ-9 and the GAD-7) were at post
      treatment 52% in the treatment group and 24% in the control group. This
      difference was significant, chi(2)(N = 100, d f = 1) = 8.3, p < .01. From post
      treatment to follow-up, treatment gains were maintained on the PHQ-9, and
      significant improvements were seen on the GAD-7. Conclusion. This study provides
      initial support for the efficacy of Internet-delivered psychodynamic therapy
      based on the affect-phobia model in the treatment of depression and anxiety
      disorders. The results support the conclusion that psychodynamic treatment
      approaches may be transferred to the guided self-help format and delivered via
      the Internet. 

PMID- 23862106
TI  - Feasibility of using microbeads with holographic barcodes to track DNA specimens
      in the clinical molecular laboratory.
AB  - We demonstrate the feasibility of using glass microbeads with a holographic
      barcode identifier to track DNA specimens in the molecular pathology laboratory.
      These beads can be added to peripheral blood specimens and are carried through
      automated DNA extraction protocols that use magnetic glass particles. We found
      that an adequate number of microbeads are consistently carried over during
      genomic DNA extraction to allow specimen identification, that the beads do not
      interfere with the performance of several different molecular assays, and that
      the beads and genomic DNA remain stable when stored together under regular
      storage conditions in the molecular pathology laboratory. The beads function as
      an internal, easily readable specimen barcode. This approach may be useful for
      identifying DNA specimens and reducing errors associated with molecular
      laboratory testing. 

PMID- 23862105
TI  - Activity in ventral premotor cortex is modulated by vision of own hand in action.
AB  - Parietal and premotor cortices of the macaque monkey contain distinct populations
      of neurons which, in addition to their motor discharge, are also activated by
      visual stimulation. Among these visuomotor neurons, a population of grasping
      neurons located in the anterior intraparietal area (AIP) shows discharge
      modulation when the own hand is visible during object grasping. Given the dense
      connections between AIP and inferior frontal regions, we aimed at investigating
      whether two hand-related frontal areas, ventral premotor area F5 and primary
      motor cortex (area F1), contain neurons with similar properties. Two macaques
      were involved in a grasping task executed in various light/dark conditions in
      which the to-be-grasped object was kept visible by a dim retro-illumination.
      Approximately 62% of F5 and 55% of F1 motor neurons showed light/dark
      modulations. To better isolate the effect of hand-related visual input, we
      introduced two further conditions characterized by kinematic features similar to
      the dark condition. The scene was briefly illuminated (i) during hand preshaping
      (pre-touch flash, PT-flash) and (ii) at hand-object contact (touch flash, T
      flash). Approximately 48% of F5 and 44% of F1 motor neurons showed a flash
      related modulation. Considering flash-modulated neurons in the two flash
      conditions, ~40% from F5 and ~52% from F1 showed stronger activity in PT- than T
      flash (PT-flash-dominant), whereas ~60% from F5 and ~48% from F1 showed stronger
      activity in T- than PT-flash (T-flash-dominant). Furthermore, F5, but not F1,
      flash-dominant neurons were characterized by a higher peak and mean discharge in
      the preferred flash condition as compared to light and dark conditions. Still
      considering F5, the distribution of the time of peak discharge was similar in
      light and preferred flash conditions. This study shows that the frontal cortex
      contains neurons, previously classified as motor neurons, which are sensitive to
      the observation of meaningful phases of the own grasping action. We conclude by
      discussing the possible functional role of these populations. 

PMID- 23862107
TI  - Optimising locational access of deprived populations to farmers' markets at a
      national scale: one route to improved fruit and vegetable consumption?
AB  - Background. Evidence suggests that improved locational access to farmers' markets
      increases fruit and vegetable (FV) consumption, particularly for low-income
      groups. Therefore, we modelled potential alternative distributions of farmers'
      markets in one country (New Zealand) to explore the potential impact for deprived
      populations and an indigenous population (Maori). Methods. Data were collected on
      current farmers' markets (n = 48), population distributions, area deprivation,
      and roads. Geographic analyses were performed to optimize market locations for
      the most deprived populations. Results. We found that, currently, farmers'
      markets provided fairly poor access for the total population: 7% within 12.5 km
      (15 min driving time); 5% within 5 km; and 3% within 2 km. Modelling the optimal
      distribution of the 48 markets substantially improved access for the most
      deprived groups: 9% (vs 2% currently) within 12.5 km; 5% (vs 1%) within 5 km; and
      3% (vs 1%) within 2 km. Access for Maori also improved: 22% (vs 7%) within 12.5
      km; 12% (vs 4%) within 5 km; and 6% (vs 2%) within 2 km. Smaller pro-equity
      results arose from optimising the locations of the 18 least pro-equity markets or
      adding 10 new markets. Conclusion. These results highlight the potential for
      improving farmers' market locations to increase accessibility for groups with low
      FV consumption. Given that such markets are easily established and relocated,
      local governments could consider these results to inform decisions, including
      subsidies for using government land and facilities. Such results can also inform
      central governments planning around voucher schemes for such markets and
      exempting them from taxes (e.g., VAT/GST). 

PMID- 23862108
TI  - Generalized linear mixed models can detect unimodal species-environment
      relationships.
AB  - Niche theory predicts that species occurrence and abundance show non-linear,
      unimodal relationships with respect to environmental gradients. Unimodal models,
      such as the Gaussian (logistic) model, are however more difficult to fit to data
      than linear ones, particularly in a multi-species context in ordination, with
      trait modulated response and when species phylogeny and species traits must be
      taken into account. Adding squared terms to a linear model is a possibility but
      gives uninterpretable parameters. This paper explains why and when generalized
      linear mixed models, even without squared terms, can effectively analyse unimodal
      data and also presents a graphical tool and statistical test to test for unimodal
      response while fitting just the generalized linear mixed model. The R-code for
      this is supplied in Supplemental Information 1. 

PMID- 23862109
TI  - Depression, anxiety and their comorbidity in the Swedish general population:
      point prevalence and the effect on health-related quality of life.
AB  - Background. Depression and anxiety disorders are major world-wide problems. There
      are no or few epidemiological studies investigating the prevalence of depression,
      generalized anxiety disorder and anxiety disorders in general in the Swedish
      population. Methods. Data were obtained by means of a postal survey administered
      to 3001 randomly selected adults. After two reminders response rate was 44.3%.
      Measures of depression and general anxiety were the 9-item Patient Health
      Questionnaire Depression Scale (PHQ-9) and the 7-item Generalized Anxiety
      Disorder Scale (GAD-7). The PHQ-9 identified participants who had experienced
      clinically significant depression (PHQ-9 >= 10), and who had a diagnosis of major
      depression (defined by using a PHQ-9 scoring algorithm). Clinically significant
      anxiety was defined as having a GAD-7 score >= 8. To specifically measure
      generalized anxiety disorder, the Generalized Anxiety Disorder Questionnaire-IV
      (GAD-Q-IV) was used with an established cut-off. Health-related quality of life
      was measured using the EuroQol (EQ-5D). Experiences of treatments for psychiatric
      disorders were also assessed. Results. Around 17.2% (95% CI: 15.1-19.4) of the
      participants were experiencing clinically significant depression (10.8%; 95% CI:
      9.1-12.5) and clinically significant anxiety (14.7%; 95% CI: 12.7-16.6). Among
      participants with either clinically significant depression or anxiety, nearly 50%
      had comorbid disorders. The point prevalence of major depression was 5.2% (95%
      CI: 4.0-6.5), and 8.8% (95% CI: 7.3-10.4) had GAD. Among those with either of
      these disorders, 28.2% had comorbid depression and GAD. There were, generally,
      significant gender differences, with more women having a disorder compared to
      men. Among those with depression or anxiety, only between half and two thirds had
      any treatment experience. Comorbidity was associated with higher symptom severity
      and lower health-related quality of life. Conclusions. Epidemiological data from
      the Swedish community collected in this study provide point prevalence rates of
      depression, anxiety disorders and their comorbidity. These conditions were shown
      in this study to be undertreated and associated with lower quality of life, that
      need further efforts regarding preventive and treatment interventions. 

PMID- 23862110
TI  - Computational insights into the neuroprotective action of riluzole on 3
      acetylpyridine-induced ataxia in rats.
AB  - OBJECTIVE: Intra-peritoneal administration of riluzole has been shown to preserve
      the membrane properties and firing characteristics of Purkinje neurons in a rat
      model of cerebellar ataxia induced by 3-acetylpyridine (3-AP). However, the exact
      mechanism(s) by which riluzole restores the normal electrophysiological
      properties of Purkinje neurons is not completely understood. Changes in the
      conductance of several ion channels, including the BK channels, have been
      proposed as a neuro protective target of riluzole. In this study, the possible
      cellular effects of riluzole on Purkinje cells from 3-AP-induced ataxic rats that
      could be responsible for its neuro protective action have been investigated by
      computer simulations. MATERIALS AND METHODS: This is a computational stimulation
      study. The simulation environment enabled a change in the properties of the
      specific ion channels as the possible mechanism of action of riluzole. This
      allowed us to study the resulted changes in the firing activity of Purkinje cells
      without concerns about its other effects and interfering parameters in the
      experiments. Simulations were performed in the NEURON environment (Version 7.1)
      in a time step of 25 MUs; analyses were conducted using MATLAB r2010a (The
      Mathworks). Data were given as mean +/- SEM. Statistical analyses were performed
      by the student's t test, and differences were considered significant if p< 0.05.
      RESULTS: The computational findings demonstrated that modulation of an individual
      ion channel current, as suggested by previous experimental studies, should not be
      considered as the only possible target for the neuro protective effects of
      riluzole to restore the normal firing activity of Purkinje cells from ataxic
      rats. CONCLUSION: Changes in the conductance of several potassium channels,
      including voltage- gated potassium (Kv1, Kv4) and big Ca(2+)-activated K(+) (BK)
      channels may be responsible for the neuro protective effect of riluzole against 3
      AP induced alterations in the firing properties of Purkinje cells in a rat model
      of ataxia.

PMID- 23862111
TI  - Investigation The Role of Gender on The HLA-DRB1 and -DQB1 Association with Type
      1 Diabetes Mellitus in Iranian Patients.
AB  - OBJECTIVE: Type 1 diabetes mellitus (T1D) is an autoimmune and multifactorial
      disorder. Subsequent analysis on human leukocyte antigen ( HLA) region shows that
      HLA-DRB1 and -DQB1 genes have the strongest association with T1D. In this study,
      for the first time, we investigated the influence of gender on the HLA-DRB1 and 
      DQB1 association with type 1 diabetes mellitus in Iranian patients in order to
      determine gender dependent HLA heterogeneity in Iranian T1D patients. MATERIALS
      AND METHODS: In this case control study, the HLA-DRB1 and -DQB1 typing were
      performed on 105 Iranian T1D patients and 100 healthy controls. The data were
      evaluated by using Fisher exact test. RESULTS: Our results indicate that
      DRB1*04:01, DQB1*03:02 alleles and DRB1*04:01- DQB1*03:02 haplotype were
      significantly more frequent in male T1D patients than females. Also, DRB1*03:01,
      DRB1*15:01, DQB1*06:01 alleles, DQB1*03:01/05:01 genotype, DRB1*03:01-DQB1*02:01
      and DRB1*15:01-DQB1*06:01 haplotypes were significantly higher in female T1D
      group than males. Furthermore, our results showed that DRB1*04:01 and DQB1*03:02
      alleles were significantly more frequent in male T1D patients 1-5 years old at
      onset than females with similar condition. The DRB1*03:01 allele and DRB1*03:01-
      DQB1*02:01 haplotype were significantly higher in female T1D patients 6-10 years
      old at onset than males with similar condition. The DRB1*15:01 allele and
      DRB1*15:01-DQB1*06:01 haplotype were significantly more frequent in female T1D
      patients 16-20 years old at onset than males with similar condition. CONCLUSION:
      Our findings suggest that gender has a significant influence on the distribution
      of HLA-DR and -DQ alleles, genotypes and haplotypes. Also, distribution of the
      HLA-DRB1 and -DQB1 alleles, genotypes and haplotypes vary based on the gender of
      T1D patients in different age at onset.

PMID- 23862112
TI  - Evaluation of Anticancer Activity of Fruit and Leave Extracts from Virus Infected
      and Healthy Cultivars of Vitis vinifera.
AB  - OBJECTIVE: Grape virus diseases are a serious problem in Iran. Leaves and fruits
      of grape have been used for different purposes like cooking in Iran. The present
      investigation was carried out to study on the cytotoxic-activities of extracts of
      fruits and leaves of Vitis vinifera from both virus-free and virus-infected grape
      cultivars against breast cancer cell line (MDAMB- 231) and human embryonic kidney
      normal cell line (HEK 293). MATERIALS AND METHODS: IN THIS EXPERIMENTAL STUDY,
      THE CONSIDERED GRAPE CULTIVARS WERE AS FOLLOWS: Rish Baba Sefid, Shahani Ghasre
      Shirin, Rotabi Zarghan, Asgari Najaf Abad, Fars, Kaj Angor Bojnord, Sarkesh
      Shiraz and Siahe Zarqan. A real-time multiplex polymerase chain reaction (real
      time Multiplex PCR) assay was applied to detect virus infected cultivars. The
      cytotoxic effect of the methanol extracts of different Vitis vinifera varieties
      on cultured cells was monitored using (3- (4, 5-Dimethylthiazol-2-yl) -2, 5
      diphenyltetrazolium bromide (MTT) assay at different concentrations (62.5, 125,
      250, 500, 750, 1000 MUg mL(-1)). RESULTS: Among these cultivars, Grapevine
      fanleaf virus (GFLV) along with related symptoms was detected in Siahe Zarqan and
      Fars. Methanolic extracts of leaves and fruits of Vitis vinifera from both virus
      free and virus infected cultivars showed a range of limited to moderate cytotoxic
      activity. However, methanol extract of leaves belonged to virus infected
      cultivars was found to have strong cytotoxic effect against MDA-MB-231 at
      different concentrations. CONCLUSION: Grapevine fanleaf virus (GFLV) can
      potentially increase the cytotoxicity of grape cultivars.

PMID- 23862113
TI  - The association of -475 and -631 interleukin-2 gene polymorphism with multiple
      sclerosis in Iranian patients.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a chronic autoimmune disease due to
      demyelination of the central nervous system. It is believed that cytokines are
      involved in the pathogenesis of MS. The interleukin-2 (IL2) gene is powerful
      functional candidate that is involved in immune regulation and operation. In this
      study, for the first time, we investigated the effect of -475 A/T and -631 G/A
      IL2 polymorphisms on MS disease in Iranian patients. MATERIALS AND METHODS: In
      this case-control study, 100 MS patients (mean age: 32.95 +/- 6.51 years, age
      range: 20-42 years) selected according to McDonald criteria, and 100 ethnically,
      sex and age matched healthy controls (mean age: 29 +/- 7.8 years, age range: 20
      52 years) with no personal or family history of autoimmune diseases were studied.
      The restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR)
      method was applied to define different alleles and genotypes of IL2 promoter
      single nucleotide polymorphism -475 A/T as well as -631 G/A among individuals.
      chi(2) was calculated and Fisher's exact test was applied to analyze the obtained
      data. The value of p < 0.05 was considered significantly . RESULTS: Evaluation of
      the -475 IL2 revealed that T allele and A/T genotype are present in 2% and 4% of
      MS patients, respectively, whereas T allele was absent in control samples. The
      comparison between alleles and genotypes in MS patients and healthy controls was
      not significant (p=0.1). For the -631 position, 1% and 2% of MS patients carried
      A allele and A/G heterozygote genotypes, respectively. All control samples had G
      allele and G/G genotype. The differences between patients and controls were not
      significant (p=0.4). Moreover, our results showed a very low frequency of T at 
      475 and A at -631 IL2 position in each of the two groups. CONCLUSION: Both -475
      and -631 IL2 polymorphisms were higher in MS patients as compared to controls,
      but the frequency differences were not significant. Based on these data, it is
      suggested that the -475 and -631 IL2 polymorphisms as functional promoter
      position may be involved in IL2 expression and regulation. To find out the exact
      effect of the mentioned SNPs on susceptibility to MS, study on a larger sample
      size is suggested.

PMID- 23862114
TI  - Determining influenza virus shedding at different time points in madin-darby
      canine kidney cell line.
AB  - OBJECTIVE: Monitoring of influenza virus shedding and optimization of
      multiplicities of infection (MOI) is important in the investigation of a virus
      one step growth cycle and for obtaining a high yield of virus in vaccine
      development and conventional basic diagnostic methods. However, eluted infectious
      viruses may still be present immediately after virus inoculation and when cells
      are washed following virus cultivation which may lead to a false positive virus
      infectivity assay. MATERIALS AND METHODS: In this experimental study, we
      investigated influenza virus progeny production in Madin-Darby canine kidney
      (MDCK) cells with five different MOI at determined time points. The results were
      analyzed by end point titration tests and immunofluorescence assay. RESULTS:
      Higher titers of eluted virus were observed following a high MOI inoculation of
      virus in cell culture. Most probably, this was the result of sialic acid residues
      from viral hemagglutin in proteins that were cleaved by neuraminidase
      glycoproteins on the surface of the influenza virus, which promoted viral spread
      from the host cell to the culture supernatant or during endocytosis, where
      viruses recycle to the cell surface by recycling endosomes which culminated in
      virus shedding without replication. CONCLUSION: We demonstrated that the pattern
      of influenza virus progeny production was dose-dependent and not uniform. This
      production was influenced by several factors, particularly MOI. Understanding the
      exact features of viral particle propagation has a major impact in producing high
      virus yields in the development of vaccines. Use of lower MOI (0.01) could result
      in accurate, precise quantitative assays in virus diagnosis and titration
      methods.

PMID- 23862115
TI  - Expression of odontogenic genes in human bone marrow mesenchymal stem cells.
AB  - OBJECTIVE: Tooth loss is a common problem and since current tooth replacement
      methods cannot counter balance with biological tooth structures, regenerating
      natural tooth structures has become an ideal goal. A challenging problem in tooth
      regeneration is to find a proper clinically feasible cell to seed.This study was
      designed to investigate the odontogenic potential of human bone marrow
      mesenchymal stem cells (HBMSCs) for seeding in tooth regeneration. MATERIALS AND
      METHODS: In this experimental study, three pregnant Sprague Dawley (SD) rats were
      used at the eleventh embryonic day and rat fetuses were removed surgically using
      semilunar flap under general anesthesia. The primary mandible was cut using a
      stereomicroscope. The epithelial and mesenchymal components were separated and
      the dissected oral epithelium was cultured for 3 days. We used flow cytometry
      analysis to confirm presence of mesenchymal stem cells and not hematopoietic
      cells and to demonstrate the presence of oral epithelium. Bone marrow mesenchymal
      stem cells (BMSCs) and cultured oral epithelium were then co-cultured for 14
      days. BMSCs cultured alone were used as controls. Expression of two odontogenic
      genes Pax9 and DMP1 was assessed using quantitative reverse transcription-
      polymerase chain reaction (RT-PCR). RESULTS: Expression of two odontogenic genes,
      Pax9 and DMP1, were detected in BMSCs co-cultured with oral epithelium but not in
      the control group. CONCLUSION: Expression of Pax9 and DMP1 by human BMSCs in the
      proximity of odontogenic epithelium indicates odontogenic potential of these
      cells.

PMID- 23862116
TI  - Promotion of remyelination by adipose mesenchymal stem cell transplantation in a
      cuprizone model of multiple sclerosis.
AB  - OBJECTIVE: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of
      the central nervous system (CNS). Stem cell transplantation is a new therapeutic
      approach for demyelinating diseases such as MS which may promote remyelination.
      In this study, we evaluate the remyelinating potential of adipose mesenchymal
      stem cells (ADSCs) and their effect on neural cell composition in the corpus
      callosum in an experimental model of MS. MATERIALS AND METHODS: This experimental
      study used adult male C57BL/6 mice. Cultured ADSCs were confirmed to be
      CD73(+),CD90(+), CD31(-),CD45(-), and labeled by PKH26. Animals were fed with
      0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. At day
      0 after cuprizone removal, mice were randomly divided into two groups: the ADSCs
      transplanted group and the control vehicle group (received medium alone). Some
      mice of the same age were fed with their normal diet to serve as healthy control
      group. Homing of ADSCs in demyelinated lesions was examined by fluorescent
      microscope. At ten days after transplantation, the mice were euthanized and their
      cells analyzed by luxol fast blue staining (LFB), transmission electron
      microscopy and flow cytometry. Results were analyzed by one-way analysis of
      variance (ANOVA). RESULTS: According to fluorescent cell labeling, transplanted
      ADSCs appeared to survive and exhibited homing specificity. LFB staining and
      transmission electron microscope evaluation revealed enhanced remyelination in
      the transplanted group compared to the control vehicle group. Flow cytometry
      analysis showedan increase in Olig2 and O4 cells and a decrease in GFAP and Iba-1
      cells in the transplanted group. CONCLUSION: Our results indicate that ADSCs may
      provide a feasible, practical way for remyelination in diseases such as MS.

PMID- 23862117
TI  - Mediterranean Fever gene analysis in the azeri turk population with familial
      mediterranean Fever: evidence for new mutations associated with disease.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive disorder
      characterized by recurrent febrile attacks accompanied by serosal and synovial
      membrane inflammation. FMF is caused by mutations in the MEFV gene and are found
      usually among Mediterranean populations, Armenians, Turks, Arabs and Jews. The
      aim of this study was to determine the frequency of MEFV gene mutations among FMF
      patients in the Azeri Turk population in North-West of Iran. MATERIALS AND
      METHODS: In this descriptive study, 130 FMF patients with Azeri Turk origin were
      screened for mutations in four exons (2, 3, 5 and10) of MEFV gene. Genomic DNA
      was extracted from whole blood and entered in ARMS-PCR and PCR-RFLP reactions.
      When cases were negative in ARMS-PCR and PCR-RFLP, the exons were amplified and
      subjected to direct sequencing. RESULTS: Our results showed that the most common
      mutations in this study population was M694V (40.19%) followed by E148Q (17.64%),
      V726A (13.72%), M680I (12.74%) and M694I (2.94%) mutations. Four new mutations
      including K618N, K716M, S614F and G136E were identified in our study. CONCLUSION:
      The prevalence of five common mutations in our study was highly similar to
      previous studies analysing the Mediterranean basin populations. Investigation by
      sequencing also revealed four new variants in the study population. The main
      genotypephenotype correlation finding was the presence of M694V mutation in
      homozygote or compound heterozygote state in the patients with renal
      manifestations.

PMID- 23862118
TI  - Impact of fixed-dose combination of germacrone, curdione, and furanodiene on
      breast cancer cell proliferation.
AB  - OBJECTIVE: Herb combination has been very popular in traditional medical
      prescriptions such as Traditional Chinese Medicine (TCM). Persistent efforts and
      attempts have been made to dissect the action mode of TCM in recent years, which
      has provided certain evidence for inter-herbal interactions. However, the
      interactions among different components in a single herb have been largely
      neglected. MATERIALS AND METHODS: In this experimental study, the interactions
      among different components of a single herb were explored. The effect of three
      main sesquiterpenes (germacrone, curdione, furanodiene) isolated from Curcuma
      WenyujinY.H.Chenet C Ling on MDA-MB-231 and MCF-7 breast cancer cell
      proliferation alone or in combination with a fixed-dose-combination was
      investigated. RESULTS: Furanodiene significantly inhibited cancer cell
      proliferation while germacrone and curdione showed no effect. Germacrone enhanced
      furanodiene's anti-proliferative effect. Curdione showed no effect on
      furanodiene's anti-proliferative effect but partly reversed the anti
      proliferative effect of germacrone and furanodiene combined. The morphological
      and mitochondrial membrane potential (Deltapsim) changes showed similar results.
      However, they demonstrated complicated interactions on the expression of
      apoptotic-related proteins and key signal transduction proteins. CONCLUSION:
      Unpredictable and complex interactions among different components in Curcuma
      WenyujinY.H.Chenet C Ling may exist. The intra-herb interactions should be taken
      into consideration when attempts are made to interpret the art of TCM formulation
      or other similar recipes.

PMID- 23862119
TI  - Three-dimensional scaffold from decellularized human gingiva for cell cultures:
      glycoconjugates and cell behavior.
AB  - OBJECTIVE: We studied both the presence of some carbohydrate compounds in a
      threedimensional (3D) matrix harvested from human gingiva and the cell behavior
      in this matrix. MATERIALS AND METHODS: In this experimental research, in order to
      prepare 3D scaffolds, human palatal gingival biopsies were harvested and
      physically decellularized by freezethawing and sodium dodecyl sulfate (SDS). The
      scaffolds were placed within the rings of blastema tissues obtained from a pinna
      rabbit, in vitro. We evaluated the presence of glycoconjugatesand cellular
      behavior according to histological, histochemical and spectrophotometry
      techniques at one, two and three weeks after culture. One-way analysis of
      variance (ANOVA)comparedthe groups. RESULTS: Extracellular matrix (ECM) remained
      after decellularization of tissue with 1% SDS. Glycoconjugate contents decreased
      meaningfully at a higher SDS concentration (p<0.0001). After culture of the ECM
      scaffold with blastema, we observed increased staining of alcian blue, periodic
      acid-Schiff (PAS) and toluidine blue in the scaffold and a number of other
      migrant cells which was caused by cell penetrationinto the scaffold.
      Spectrophotometry results showed an increase in glycosaminoglycans (GAGs) of the
      decellularized scaffolds at three weeks after culture. CONCLUSION: The present
      study has shown that a scaffold generated from palatal gingival tissue ECM is a
      suitable substrate for blastema cell migration and activity.This scaffold
      maypotentially be useful as a biological scaffold in tissue engineering
      applications.

PMID- 23862120
TI  - Prevention and Inhibition of TC-1 Cell Growth in Tumor Bearing Mice by HPV16 E7
      Protein in Fusion with Shiga Toxin B-Subunit from shigella dysenteriae.
AB  - OBJECTIVE: For immunotherapy of human papillomavirus (HPV) -16-associated
      cervical cancers the E7 protein is considered a prime candidate. However it is a
      poor inducer of cytotoxic T-cell response, when being used as a singular antigen
      in protein vaccination. Hence, in this study we focused on the utilization of a
      vaccine delivery system for prevention or treatment of cervical cancer. MATERIALS
      AND METHODS: In this experimental study, we designed and evaluated a novel fusion
      protein comprising HPV16 E7 antigen fused to Shiga toxin B-subunit (STxB) as both
      an antigen vector and an adjuvant. Then we designed two preventive and
      therapeutic tumor models to investigate the prevention and inhibition of TC-1
      cell growth in female C57BL/6 mice, respectively. In each model, mice were
      immunized with the recombinant protein of E7-STxB or E7 without any adjuvant.
      RESULTS: We demonstrated that prophylactic immunization of E7-STxB protected mice
      against TC-1 cells. Also in the therapeutic model, E7-STxB inhibited TC-1 tumor
      growth inlungs. The results were significant when compared with the immunization
      of E7 singularly. CONCLUSION: We concluded that immunization with the E7-STxB
      protein without any adjuvant could generate anti-tumor effect in mice challenged
      with TC-1 cells.This research verifies the clinical applications and the future
      prospects of developing HPV16 E7 therapeutic vaccines fused to immunoadjuvants.

PMID- 23862121
TI  - Multiple Genotypes of the Commonly Co-Segregating Toll-Like Receptor 4 Asp299Gly
      and Thr399Ile in Baluchi Malaria Patients from Iran.
AB  - OBJECTIVE: Different studies have shown an association of TLR4 polymorphisms with
      susceptibility/resistance to malaria disease. In the current immunogenetic study,
      we assessed the TLR4 genotypes formed by the two common single nucleotide
      polymorphisms (SNPs) (Asp299Gly and Thr399Ile) in the co-segregate state in
      Baluchi Plasmodium falciparum infected and healthy populations from malaria
      hypoendemic areas of Iran. The study was performed to evaluate the distribution
      and correlation of TLR4 co-segregating genotypes in patients with mild malaria.
      Moreover, the frequency of these genotypes was compared with reported results
      from other populations in similar or contrasting malaria settings around the
      world. MATERIALS AND METHODS: In this case control study, the presence of 2 SNPs
      in the TLR4 gene (Asp299Gly and Thr399Ile) were analyzed in 350 Baluchi patients
      with mild malaria and 350 unrelated healthy controls by using polymerase chain
      reaction/restriction fragment length polymorphism (PCR/RFLP) techniques followed
      by sequencing analysis. Differences in the TLR4 co-segregate genotype frequencies
      among the studied group were determined by Fisher's exact test. RESULTS: Although
      the distribution of the two commonly co-segregating TLR4 genotypes presented a
      diverse and distinct pattern in the Baluchi population, no significant difference
      was detected between the cases and controls (p>0.05). A lower frequency of TLR4
      Asp299Gly/Thr399Thr was observed in Baluchis with mild malaria compared to
      African populations (p< 0.05). CONCLUSION: Differences in the co-segregation
      patterns of TLR4 Asp299Gly/Thr399Ile genotypes in the Baluchi population compared
      to other malaria endemic populations may suggest different local evolutionary
      pressure on TLR4 polymorphisms by malaria in this region. The higher frequency of
      Asp299Gly/Thr399Ile genotypes among the Baluchi population compared with the
      African population (p< 0.05) which suffers from a larger number of severe cases
      might suggest that this genotype has a role in protecting against severe malaria.
      These findings are useful for further understanding the pathogenesis of severe
      malaria.

PMID- 23862122
TI  - Cloning, expression, and functional characterization of in-house prepared human
      leukemia inhibitory factor.
AB  - OBJECTIVE: Leukemia inhibitory factor (LIF) plays important roles in cellular
      proliferation, growth promotion and differentiation of various types of target
      cells. In addition, LIF influences bone metabolism, cachexia, neural development,
      embryogenesis and inflammation. Human LIF (hLIF) is an essential growth factor
      for the maintenance of mouse embryonic stem cells (ESCs) and induced pluripotent
      stem cells (iPSCs) in a pluripotent, undifferentiated state. MATERIALS AND
      METHODS: In this experimental study, we cloned hLIF into the pENTR-D/ TOPO entry
      vector by a TOPO reaction. Next, hLIF was subcloned into the pDEST17 destination
      vector by the LR reaction, which resulted in the production of a construct that
      was transferred into E. coli strain Rosetta-gamiTM 2(DE3) pLacI competent cells
      to produce the His6-hLIF fusion protein. RESULTS: This straightforward method
      produced a biologically active recombinant hLIF protein in E. coli that has long
      term storage ability. This procedure has provided rapid, cost effective
      purification of a soluble hLIF protein that is biologically active and functional
      as measured in mouse ESCs and iPSCs in vitro. CONCLUSION: Our results showed no
      significant differences in function between laboratory produced and
      commercialized hLIF.

PMID- 23862123
TI  - Significance of secreted protein acidic and rich in cysteine expression in
      colorectal carcinoma.

PMID- 23862124
TI  - Clinical significance of the metastatic lymph-node ratio in rectal cancer.

PMID- 23862125
TI  - Individualized Cutoff Value of the Serum Carcinoembryonic Antigen Level According
      to TNM Stage in Colorectal Cancer.

PMID- 23862126
TI  - Expression of Secreted Protein Acidic and Rich in Cysteine in the Stroma of a
      Colorectal Carcinoma is Associated With Patient Prognosis.
AB  - PURPOSE: Secreted protein acidic and rich in cysteine (SPARC), also known as
      osteonectin or basement-membrane-40 (BM-40), is a member of a family of
      matricellular proteins, whose functions are to modulate cell-matrix interactions,
      growth and angiogenesis in colorectal cancer. In this study, the expression of
      SPARC was evaluated and its correlations with clinicopathological parameters were
      investigated. METHODS: The researchers analyzed the expression patterns of SPARC
      by using immunohistochemistry in 332 cases of colorectal cancer of tissue
      microarray. The clinicopathological characteristics were defined by using the TNM
      criteria of the Union for International Cancer Control. Clinicopathological
      factors such as age, sex, histologic type of the tumor, pathologic tumor stage,
      TNM stage, and lymphovascular invasion were evaluated according to the SPARC
      expression. RESULTS: The hazard ratios expressing SPARC in tumor cells, in the
      stroma, and in both tumor cells and the stroma were 2.10 (P = 0.036), 3.27 (P =
      0.003) and 2.12 (P = 0.038), respectively. Patient survival was decreased in
      patient expressing SPARC in the stroma, and this result showed statistical
      significance (P = 0.016). CONCLUSION: These findings suggest that SPARC
      expression in a tumor and in the stroma correlates with disease progression and
      may be used as a prognostic marker for colorectal cancer.

PMID- 23862127
TI  - Prognostic impact of the metastatic lymph node ratio on survival in rectal
      cancer.
AB  - PURPOSE: Lymph-node metastasis is the most important predictor of survival in
      stage III rectal cancer. The number of metastatic lymph nodes may vary depending
      on the level of specimen dissection and the total number of lymph nodes
      harvested. The aim of this study was to evaluate whether the lymph node ratio
      (LNR) is a prognostic parameter for patients with rectal cancer. METHODS: A
      retrospective review of a database of rectal cancer patients was performed to
      determine the effect of the LNR on the disease-free survival (DFS) and the
      overall survival. Of the total 228 patients with rectal cancer, 55 patients with
      stage III cancer were eligible for analysis. Survival curves were estimated using
      the Kaplan-Meier method. Cox regression analyses, after adjustments for potential
      confounders, were used to evaluate the relationship between the LNR and survival.
      RESULTS: According to the cutoff point 0.15 (15%), the 2-year DFS was 95.2% among
      patients with a LNR < 0.15 compared with 67.6% for those with LNR >= 0.15 (P =
      0.02). In stratified and multivariate analyses adjusted for age, gender,
      histology and tumor status, a higher LNR was independently associated with worse
      DFS. CONCLUSION: This study showed the prognostic significance of ratio-based
      staging for rectal cancer and may help in developing better staging systems. LNR
      0.15 (15%) was shown to be a cutoff point for determining survival and prognosis
      in rectal cancer cases.

PMID- 23862128
TI  - Individualized Cutoff Value of the Preoperative Carcinoembryonic Antigen Level is
      Necessary for Optimal Use as a Prognostic Marker.
AB  - PURPOSE: Carcinoembryonic antigen (CEA) is an important prognostic marker in
      colorectal cancer (CRC). However, in some stages, it does not work. We performed
      this study to find a way in which preoperative CEA could be used as a constant
      prognostic marker in harmony with the TNM staging system. METHODS: Preoperative
      CEA levels and recurrences in CRC were surveyed. The distribution of CEA levels
      and the recurrences in each TNM stage of CRC were analyzed. An optimal cutoff
      value for each TNM stage was calculated and tested for validity as a prognostic
      marker within the TNM staging system. RESULTS: The conventional cutoff value of
      CEA (5 ng/mL) was an independent prognostic factor on the whole. However, when
      evaluated in subgroups, it was not a prognostic factor in stage I or stage III of
      N2. A subgroup analysis according to TNM stage revealed different CEA
      distributions and recurrence rates corresponding to different CEA ranges. The
      mean CEA levels were higher in advanced stages. In addition, the recurrence rates
      of corresponding CEA ranges were higher in advanced stages. Optimal cutoff values
      from the receiver operating characteristic curves were 7.4, 5.5, and 4.5 ng/mL
      for TNM stage I, II, and III, respectively. Those for N0, N1, and N2 stages were
      5.5, 4.8, and 3.5 ng/mL, respectively. The 5-year disease-free survivals were
      significantly different according to these cutoff values for each TNM and N
      stage. The multivariate analysis confirmed the new cutoff values to be more
      efficient in discriminating the prognosis in the subgroups of the TNM stages.
      CONCLUSION: Individualized cutoff values of the preoperative CEA level are a more
      practical prognostic marker following and in harmony with the TNM staging system.

PMID- 23862129
TI  - Prognostic significance of the decreased rate of perioperative serum
      carcinoembryonic antigen level in the patients with colon cancer after a curative
      resection.
AB  - PURPOSE: The serum level of carcinoembryonic antigen (CEA) is a clinical
      prognostic factor in the follow-up evaluation of patients with colon cancer. We
      aimed to evaluate the prognostic significance of the rate of decrease of the
      perioperative serum CEA level in patients with colon cancer after a curative
      resection. METHODS: A total of 605 patients who underwent a curative resection
      for colon cancer between January 2000 and December 2007 were enrolled
      retrospectively. The rate of decrease was calculated using the following
      equation: ([preoperative CEA - postoperative CEA]/[preoperative CEA] *100).
      RESULTS: In the group with a preoperative serum CEA level of >5 ng/mL, the
      normalized group with a postoperative serum CEA level of <=5 ng/mL showed a
      better overall survival (OS) rate and disease-free survival (DFS) rate than those
      of the non-normalized group (P <= 0.0001). The "cutoff values" of the rate of
      decrease in the perioperative serum CEA that determined the OS and the DFS were
      48.9% and 50.8%, respectively. In the multivariate analysis of preoperative serum
      CEA levels >5 ng/mL, the prognostic factors for the OS and the DFS were the
      cutoff value (P < 0.0001) and the pN stage (P < 0.0001). CONCLUSION: A rate of
      decrease of more than 50% in the perioperative serum CEA level, as well as the
      normalization of the postoperative serum CEA level, may be useful factors for
      determining a prognosis for colon cancer patients with high preoperative CEA
      levels.

PMID- 23862130
TI  - Primary multiple mesenteric liposarcoma of the transverse mesocolon.
AB  - Liposarcomas are common tumors arising in the retroperitoneum. However, a primary
      mesenteric liposarcoma is a rare entity and less than 50 cases have been reported
      so far. Further, a liposarcoma arising in the transverse mesocolon is very
      unusual, and cases of multiple primary tumors arising from the transverse
      mesocolon are extremely rare. We want to report a case of a multiple primary
      mesenteric liposarcoma arising from the transverse mesocolon in a 63-year-old
      female who was successfully treated by surgery. Because a primary mesenteric
      liposarcoma is a rare entity, it should be considered with the differential
      diagnosis of an abdominal mesenchymal tumor. It can be diagnosed preoperatively
      by using contrast enhanced computed tomography and magnetic resonance imaging.
      The treatment for such a liposarcoma is surgical resection with sufficient
      surgical margin; the role of adjuvant therapy has yet to be defined. 

PMID- 23862131
TI  - Intramural recurrence without mucosal lesions after an endoscopic mucosal
      resection for early colorectal cancer.
AB  - Advances in endoscopic instruments and techniques have enabled increased
      detection and removal of early colorectal cancer (ECC), which is defined as a
      tumor whose invasion is limited to the mucosa or submucosa. Some cases can be
      treated by endoscopic mucosal resection (EMR). However, local recurrence
      frequently occurs after an EMR for ECC. The recurrence pattern is usually
      intramural recurrence with a mucosal lesion at the EMR's site. We report the
      cases of two patients with intramural recurrence without mucosal lesions after an
      EMR for ECC. These cases indicate that a local recurrence after an EMR for ECC
      can appear as an intramural recurrence without mucosal lesions at a previous EMR
      site or another site, although this presentation is very unusual. 

PMID- 23862132
TI  - Mucosal schwann-cell hamartoma diagnosed by using an endoscopic snare
      polypectomy.
AB  - Colorectal polyps of mesenchymal origin are a rare group of colorectal disorders.
      A "mucosal Schwann-cell hamartoma," which is one type of polypoid lesion that
      originates from the mesenchyme, is a newly-proposed disease entity to be
      distinguished from the neurofibromas found in type-1 neurofibromatosis. This
      lesion is composed of pure Schwann-cell proliferation in the lamina propria and
      shows diffuse immunoreactivity for the S-100 protein. We report a case of a
      polypoid lesion of the colon with the features of this recently-proposed disease
      entity. 

PMID- 23862133
TI  - Two Novel 30K Proteins Overexpressed in Baculovirus System and Their
      Antiapoptotic Effect in Insect and Mammalian Cells.
AB  - The 30K family of proteins is important in energy metabolism and may play a role
      in inhibiting cellular apoptosis in silkworms (Bombyx mori). Several 30K-family
      proteins have been identified. In this study, two new silkworm genes, referred to
      as Slp (NM 001126256) and Lsp-t (NM 001043443), were analyzed by a bioinformatics
      approach according to the sequences of 30K proteins previously reported in the
      silkworm. Both Slp and Lsp-t shared more than 41% amino acid sequence homology
      with the reported 30K proteins and displayed a conserved domain consistent with
      that of lipoprotein-11. Additionally, the cDNA sequences of both Slp and Lsp-t
      were obtained from the fat bodies of silkworm larvae by reverse transcription
      polymerase chain reaction. Both genes were expressed in BmN cells using the Bac
      to-Bac system. Purified Slp and Lsp-t were added to cultured BmN and human
      umbilical vein endothelial cells (HUVEC) that were treated with H2O2. Both Slp
      and Lsp-t significantly enhanced the viability and suppressed DNA fragmentation
      in H2O2 treated BmN and HUVEC cells. This study suggested that Slp and Lsp-t
      exhibit similar biological activities as their known 30K-protein counterparts and
      mediate an inhibitory effect against H2O2-induced apoptosis. 

PMID- 23862135
TI  - New applications of photodynamic therapy in biomedicine and biotechnology.

PMID- 23862134
TI  - Effect of ex vivo culture conditions on immunosuppression by human mesenchymal
      stem cells.
AB  - A microarray analysis was performed to investigate whether ex vivo culture
      conditions affect the characteristics of MSCs. Gene expression profiles were
      mainly influenced by the level of cell confluence rather than initial seeding
      density. The analysis showed that 276 genes were upregulated and 230 genes
      downregulated in MSCs harvested at ~90% versus ~50% confluence (P < 0.05, FC >
      2). The genes that were highly expressed in MSCs largely corresponded to
      chemotaxis, inflammation, and immune responses, indicating direct or indirect
      involvement in immunomodulatory functions. Specifically, PTGES and ULBP1 were up
      regulated in MSCs harvested at high density. Treatment of MSCs with PTGES or
      ULBP1 siRNA reversed their inhibition of T-cell proliferation in vitro. The
      culture conditions such as cell confluence at harvest seem to be important for
      gene expression profile of MSCs; therefore, the results of this study may provide
      useful guidelines for the harvest of MSCs that can appropriately suppress the
      immune response. 

PMID- 23862136
TI  - Magnetofection: a reproducible method for gene delivery to melanoma cells.
AB  - Magnetofection is a nanoparticle-mediated approach for transfection of cells,
      tissues, and tumors. Specific interest is in using superparamagnetic iron oxide
      nanoparticles (SPIONs) as delivery system of therapeutic genes. Magnetofection
      has already been described in some proof-of-principle studies; however, fine
      tuning of the synthesis of SPIONs is necessary for its broader application.
      Physicochemical properties of SPIONs, synthesized by the co-precipitation in an
      alkaline aqueous medium, were tested after varying different parameters of the
      synthesis procedure. The storage time of iron(II) sulfate salt, the type of
      purified water, and the synthesis temperature did not affect physicochemical
      properties of SPIONs. Also, varying the parameters of the synthesis procedure did
      not influence magnetofection efficacy. However, for the pronounced gene
      expression encoded by plasmid DNA it was crucial to functionalize poly(acrylic)
      acid-stabilized SPIONs (SPIONs-PAA) with polyethyleneimine (PEI) without the
      adjustment of its elementary alkaline pH water solution to the physiological pH.
      In conclusion, the co-precipitation of iron(II) and iron(III) sulfate salts with
      subsequent PAA stabilization, PEI functionalization, and plasmid DNA binding is a
      robust method resulting in a reproducible and efficient magnetofection. To
      achieve high gene expression is important, however, the pH of PEI water solution
      for SPIONs-PAA functionalization, which should be in the alkaline range. 

PMID- 23862138
TI  - A simple model for assessment of anti-toxin antibodies.
AB  - The toxins associated with infectious diseases are potential targets for
      inhibitors which have the potential for prophylactic or therapeutic use. Many
      antibodies have been generated for this purpose, and the objective of this study
      was to develop a simple mathematical model that may be used to evaluate the
      potential protective effect of antibodies. This model was used to evaluate the
      contributions of antibody affinity and concentration to reducing antibody
      receptor complex formation and internalization. The model also enables prediction
      of the antibody kinetic constants and concentration required to provide a
      specified degree of protection. We hope that this model, once validated
      experimentally, will be a useful tool for in vitro selection of potentially
      protective antibodies for progression to in vivo evaluation. 

PMID- 23862139
TI  - Long noncoding RNA HOTAIR is associated with motility, invasion, and metastatic
      potential of metastatic melanoma.
AB  - Metastatic melanoma, the primary cause of skin cancer-related death, warrants new
      therapeutic approaches that target the regulatory machinery at molecular level.
      While long noncoding RNAs (lncRNAs) are dysregulated in a number of cancer types,
      limited data are available on the expression and function of lncRNAs in melanoma
      metastasis. The primary objective of this study was to investigate the role of 6
      metastasis-related lncRNAs in pairs of primary melanoma and matched lymph node
      metastatic tissues. Among the tested lncRNAs, HOTAIR was the most highly
      expressed in lymph node metastasis. The role of HOTAIR in melanoma cell motility
      and invasion was further evaluated by knocking down HOTAIR with siRNAs. Knockdown
      of HOTAIR resulted in the reduction of motility and invasion of human melanoma
      cell line A375, as assessed by wound healing assay and Matrigel-based invasion
      assay. siHOTAIR also suppressed the degradation of gelatin matrix, suggesting
      that HOTAIR promotes gelatinase activity. Together, our study shows that HOTAIR
      is overexpressed in metastatic tissue, which is associated with the ability of
      HOTAIR to promote melanoma cell motility and invasion. These data indicate that
      lncRNAs may be involved in the metastasis of melanoma and provide support for
      further evaluation of lncRNAs in melanoma. 

PMID- 23862137
TI  - Extracellular matrix degradation and tissue remodeling in periprosthetic
      loosening and osteolysis: focus on matrix metalloproteinases, their endogenous
      tissue inhibitors, and the proteasome.
AB  - The leading complication of total joint replacement is periprosthetic osteolysis,
      which often results in aseptic loosening of the implant, leading to revision
      surgery. Extracellular matrix degradation and connective tissue remodeling around
      implants have been considered as major biological events in the periprosthetic
      loosening. Critical mediators of wear particle-induced inflammatory osteolysis
      released by periprosthetic synovial cells (mainly macrophages) are inflammatory
      cytokines, chemokines, and proteolytic enzymes, mainly matrix metalloproteinases
      (MMPs). Numerous studies reveal a strong interdependence of MMP expression and
      activity with the molecular mechanisms that control the composition and turnover
      of periprosthetic matrices. MMPs can either actively modulate or be modulated by
      the molecular mechanisms that determine the debris-induced remodeling of the
      periprosthetic microenvironment. In the present study, the molecular mechanisms
      that control the composition, turnover, and activity of matrix macromolecules
      within the periprosthetic microenvironment exposed to wear debris are summarized
      and presented. Special emphasis is given to MMPs and their endogenous tissue
      inhibitors (TIMPs), as well as to the proteasome pathway, which appears to be an
      elegant molecular regulator of specific matrix macromolecules (including specific
      MMPs and TIMPs). Furthermore, strong rationale for potential clinical
      applications of the described molecular mechanisms to the treatment of
      periprosthetic loosening and osteolysis is provided. 

PMID- 23862140
TI  - Influence of heavy metal stress on antioxidant status and DNA damage in Urtica
      dioica.
AB  - Heavy metals have the potential to interact and induce several stress responses
      in the plants; thus, effects of heavy metal stress on DNA damages and total
      antioxidants level in Urtica dioica leaves and stems were investigated. The
      samples are sampled from areas with different metal exposition. Metal content was
      analyzed by Inductively Coupled Plasma-Atomic Emission Spectrometer (ICP-AES),
      for total antioxidants level assessment the Ferric-Reducing Antioxidant Power
      (FRAP) assay was used, and genomic DNA isolation from frozen plant samples was
      performed to obtain DNA fingerprints of investigated plant. It was found that
      heavy metal contents in stems generally changed synchronously with those in
      leaves of the plant, and extraneous metals led to imbalance of mineral nutrient
      elements. DNA damages were investigated by Random Amplified Polymorphic DNA
      (RAPD) technique, and the results demonstrated that the samples exposed to metals
      yielded a large number of new fragments (total 12) in comparison with the control
      sample. This study showed that DNA stability is highly affected by metal
      pollution which was identified by RAPD markers. Results suggested that heavy
      metal stress influences antioxidant status and also induces DNA damages in U.
      dioica which may help to understand the mechanisms of metals genotoxicity. 

PMID- 23862141
TI  - Effects of electromagnetic fields on osteogenesis of human alveolar bone-derived
      mesenchymal stem cells.
AB  - This study was performed to investigate the effects of extremely low frequency
      pulsed electromagnetic fields (ELF-PEMFs) on the proliferation and
      differentiation of human alveolar bone-derived mesenchymal stem cells (hABMSCs).
      Osteogenesis is a complex series of events involving the differentiation of
      mesenchymal stem cells to generate new bone. In this study, we examined not
      merely the effect of ELF-PEMFs on cell proliferation, alkaline phosphatase (ALP)
      activity, and mineralization of the extracellular matrix but vinculin, vimentin,
      and calmodulin (CaM) expressions in hABMSCs during osteogenic differentiation.
      Exposure of hABMSCs to ELF-PEMFs increased proliferation by 15% compared to
      untreated cells at day 5. In addition, exposure to ELF-PEMFs significantly
      increased ALP expression during the early stages of osteogenesis and
      substantially enhanced mineralization near the midpoint of osteogenesis within 2
      weeks. ELF-PEMFs also increased vinculin, vimentin, and CaM expressions, compared
      to control. In particular, CaM indicated that ELF-PEMFs significantly altered the
      expression of osteogenesis-related genes. The results indicated that ELF-PEMFs
      could enhance early cell proliferation in hABMSCs-mediated osteogenesis and
      accelerate the osteogenesis. 

PMID- 23862142
TI  - Preparation, modification, and characterization of alginate hydrogel with nano
      /microfibers: a new perspective for tissue engineering.
AB  - We aimed to develop an alginate hydrogel (AH) modified with nano-/microfibers of
      titanium dioxide (nfTD) and hydroxyapatite (nfHY) and evaluated its biological
      and chemical properties. Nano-/microfibers of nfTD and nfHY were combined with
      AH, and its chemical properties were evaluated by FTIR spectroscopy, X-ray
      diffraction, energy dispersive X-Ray analysis, and the cytocompatibility by the
      WST-1 assay. The results demonstrate that the association of nfTD and nfHY nano
      /microfibers to AH did not modified the chemical characteristics of the scaffold
      and that the association was not cytotoxic. In the first 3 h of culture with
      NIH/3T3 cells nfHY AH scaffolds showed a slight increase in cell viability when
      compared to AH alone or associated with nfTD. However, an increase in cell
      viability was observed in 24 h when nfTD was associated with AH scaffold. In
      conclusion our study demonstrates that the combination of nfHY and nfTD nano
      /microfibers in AH scaffold maintains the chemical characteristics of alginate
      and that this association is cytocompatible. Additionally the combination of nfHY
      with AH favored cell viability in a short term, and the addition of nfTD
      increased cell viability in a long term.

PMID- 23862143
TI  - Clinical application of magnetic resonance imaging in management of breast cancer
      patients receiving neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy (NAC), also termed primary, induction, or preoperative
      chemotherapy, is traditionally used to downstage inoperable breast cancer. In
      recent years it has been increasingly used for patients who have operable cancers
      in order to facilitate breast-conserving surgery, achieve better cosmetic
      outcome, and improve prognosis by reaching pathologic complete response (pCR).
      Many studies have demonstrated that magnetic resonance imaging (MRI) can assess
      residual tumor size after NAC, and that provides critical information for
      planning of the optimal surgery. NAC also allows for timely adjustment of
      administered drugs based on response, so ineffective regimens could be terminated
      early to spare patients from unnecessary toxicity while allowing other effective
      regimens to work sooner. This review article summarizes the clinical application
      of MRI during NAC. The use of different MR imaging methods, including dynamic
      contrast-enhanced MRI, proton MR spectroscopy, and diffusion-weighted MRI, to
      monitor and evaluate the NAC response, as well as how changes of parameters
      measured at an early time after initiation of a drug regimen can predict final
      treatment outcome, are reviewed. MRI has been proven a valuable tool and will
      continue to provide important information facilitating individualized image
      guided treatment and personalized management for breast cancer patients
      undergoing NAC. 

PMID- 23862145
TI  - Simultaneous reduction in noise and cross-contamination artifacts for dual-energy
      X-ray CT.
AB  - PURPOSE: Dual-energy CT imaging tends to suffer from much lower signal-to-noise
      ratio than single-energy CT. In this paper, we propose an improved anticorrelated
      noise reduction (ACNR) method without causing cross-contamination artifacts.
      METHODS: The proposed algorithm diffuses both basis material density images
      (e.g., water and iodine) at the same time using a novel correlated diffusion
      algorithm. The algorithm has been compared to the original ACNR algorithm in a
      contrast-enhanced, IRB-approved patient study. Material density accuracy and
      noise reduction are quantitatively evaluated by the percent density error and the
      percent noise reduction. RESULTS: Both algorithms have significantly reduced the
      noises of basis material density images in all cases. The average percent noise
      reduction is 69.3% and 66.5% with the ACNR algorithm and the proposed algorithm,
      respectively. However, the ACNR algorithm alters the original material density by
      an average of 13% (or 2.18 mg/cc) with a maximum of 58.7% (or 8.97 mg/cc) in this
      study. This is evident in the water density images as massive cross
      contaminations are seen in all five clinical cases. On the contrary, the proposed
      algorithm only changes the mean density by 2.4% (or 0.69 mg/cc) with a maximum of
      7.6% (or 1.31 mg/cc). The cross-contamination artifacts are significantly
      minimized or absent with the proposed algorithm. CONCLUSION: The proposed
      algorithm can significantly reduce image noise present in basis material density
      images from dual-energy CT imaging, with minimized cross-contaminations compared
      to the ACNR algorithm.

PMID- 23862144
TI  - Identification of opportunistic pathogenic bacteria in drinking water samples of
      different rural health centers and their clinical impacts on humans.
AB  - International drinking water quality monitoring programs have been established in
      order to prevent or to reduce the risk of contracting water-related infections. A
      survey was performed on groundwater-derived drinking water from 13 different
      hospitals in the Mahabubnagar District. A total of 55 bacterial strains were
      isolated which belonged to both gram-positive and gram-negative bacteria. All the
      taxa were identified based on the 16S rRNA gene sequence analysis based on which
      they are phylogenetically close to 27 different taxa. Many of the strains are
      closely related to their phylogenetic neighbors and exhibit from 98.4 to 100%
      sequence similarity at the 16S rRNA gene sequence level. The most common group
      was similar to Acinetobacter junii (21.8%) and Acinetobacter calcoaceticus
      (10.9%) which were shared by 7 and 5 water samples, respectively. Out of 55
      isolates, only 3 isolates belonged to coliform group which are Citrobacter
      freundii and Pantoea anthophila. More than half (52.7%, 29 strains) of the
      phylogenetic neighbors which belonged to 12 groups were reported to be pathogenic
      and isolated from clinical specimens. Out of 27 representative taxa are
      affiliated have eight representative genera in drinking water except for those
      affiliated with the genera Exiguobacterium, Delftia, Kocuria, and Lysinibacillus.

PMID- 23862146
TI  - Characterization of antibiotic-loaded alginate-OSA starch microbeads produced by
      ionotropic pregelation.
AB  - The aim of this study was to characterize the penicillin-loaded microbeads
      composed of alginate and octenyl succinic anhydride (OSA) starch prepared by
      ionotropic pregelation with calcium chloride and to evaluate their in vitro drug
      delivery profile. The beads were characterized by size, scanning electron
      microscopy (SEM), zeta potential, swelling behavior, and degree of erosion. Also,
      the possible interaction between penicillin and biopolymers was investigated by
      differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), and
      Fourier transform infrared (FTIR) analysis. The SEM micrograph results indicated
      a homogeneous drug distribution in the matrix. Also, based on thermal analyses
      (TGA/DSC), interactions were detected between microbead components. Although FTIR
      spectra of penicillin-loaded microbeads did not reveal the formation of new
      chemical entities, they confirmed the chemical drug stability. XRD patterns
      showed that the incorporated crystalline structure of penicillin did not
      significantly alter the primarily amorphous polymeric network. In addition, the
      results confirmed a prolonged penicillin delivery system profile. These results
      imply that alginate and OSA starch beads can be used as a suitable controlled
      release carrier for penicillin. 

PMID- 23862148
TI  - Deciphering the intracellular fate of Propionibacterium acnes in macrophages.
AB  - Propionibacterium acnes is a Gram-positive bacterium that colonizes various
      niches of the human body, particularly the sebaceous follicles of the skin. Over
      the last years a role of this common skin bacterium as an opportunistic pathogen
      has been explored. Persistence of P. acnes in host tissue has been associated
      with chronic inflammation and disease development, for example, in prostate
      pathologies. This study investigated the intracellular fate of P. acnes in
      macrophages after phagocytosis. In a mouse model of P. acnes-induced chronic
      prostatic inflammation, the bacterium could be detected in prostate-infiltrating
      macrophages at 2 weeks postinfection. Further studies performed in the human
      macrophage cell line THP-1 revealed intracellular survival and persistence of P.
      acnes but no intracellular replication or escape from the host cell. Confocal
      analyses of phagosome acidification and maturation were performed. Acidification
      of P. acnes-containing phagosomes was observed at 6 h postinfection but then lost
      again, indicative of cytosolic escape of P. acnes or intraphagosomal pH
      neutralization. No colocalization with the lysosomal markers LAMP1 and cathepsin
      D was observed, implying that the P. acnes-containing phagosome does not fuse
      with lysosomes. Our findings give first insights into the intracellular fate of
      P. acnes; its persistency is likely to be important for the development of P.
      acnes-associated inflammatory diseases. 

PMID- 23862147
TI  - Stability and accuracy assessment of identification of traditional Chinese
      materia medica using DNA barcoding: a case study on Flos Lonicerae Japonicae.
AB  - DNA barcoding is a novel molecular identification method that aids in identifying
      traditional Chinese materia medica using traditional identification techniques.
      However, further study is needed to assess the stability and accuracy of DNA
      barcoding. Flos Lonicerae Japonicae, a typical medicinal flower, is widely used
      in China, Korea, and other Southeast Asian countries. However, Flos Lonicerae
      Japonicae and its closely related species have been misused and traded at varying
      for a wide range of prices. Therefore, Flos Lonicerae Japonicae must be
      accurately identified. In this study, the ITS2 and psbA-trnH regions were
      amplified by polymerase chain reaction (PCR). Sequence assembly was performed
      using CodonCode Aligner V 3.5.4. The intra- versus inter-specific variations were
      assessed using six metrics and "barcoding gaps." Species identification was
      conducted using BLAST1 and neighbor-joining (NJ) trees. Results reveal that ITS2
      and psbA-trnH exhibited an average intraspecific divergence of 0.001 and 0,
      respectively, as well as an average inter-specific divergence of 0.0331 and
      0.0161. The identification efficiency of ITS2 and psbA-trnH evaluated using
      BLAST1 was 100%. Flos Lonicerae Japonicae was formed into one clade through the
      NJ trees. Therefore, Flos Lonicerae Japonicae can be stably and accurately
      identified through the ITS2 and psbA-trnH regions, respectively.

PMID- 23862149
TI  - Genetic dissection of new genotypes of drumstick tree (Moringa oleifera Lam.)
      using random amplified polymorphic DNA marker.
AB  - The knowledge of genetic diversity of tree crop is very important for breeding
      and improvement program for the purpose of improving the yield and quality of its
      produce. Genetic diversity study and analysis of genetic relationship among 20
      Moringa oleifera were carried out with the aid of twelve primers from, random
      amplified polymorphic DNA marker. The seeds of twenty M. oleifera genotypes from
      various origins were collected and germinated and raised in nursery before
      transplanting to the field at University Agricultural Park (TPU). Genetic
      diversity parameter, such as Shannon's information index and expected
      heterozygosity, revealed the presence of high genetic divergence with value of
      1.80 and 0.13 for Malaysian population and 0.30 and 0.19 for the international
      population, respectively. Mean of Nei's gene diversity index for the two
      populations was estimated to be 0.20. In addition, a dendrogram constructed,
      using UPGMA cluster analysis based on Nei's genetic distance, grouped the twenty
      M. oleifera into five distinct clusters. The study revealed a great extent of
      variation which is essential for successful breeding and improvement program.
      From this study, M. oleifera genotypes of wide genetic origin, such as T-01, T
      06, M-01, and M-02, are recommended to be used as parent in future breeding
      program. 

PMID- 23862150
TI  - Bioactive surface modification of hydroxyapatite.
AB  - The purpose of this study was to establish an acid-etching procedure for altering
      the Ca/P ratio of the nanostructured surface of hydroxyapatite (HAP) by using
      surface chemical and morphological analyses (XPS, XRD, SEM, surface roughness,
      and wettability) and to evaluate the in vitro response of osteoblast-like cells
      (MC3T3-E1 cells) to the modified surfaces. This study utilized HAP and HAP
      treated with 10%, 20%, 30%, 40%, 50%, or 60% phosphoric acid solution for 10
      minutes at 25 degrees C, followed by rinsing 3 times with ultrapure water. The
      30% phosphoric acid etching process that provided a Ca/P ratio of 1.50, without
      destruction of the grain boundary of HAP, was selected as a surface-modification
      procedure. Additionally, HAP treated by the 30% phosphoric acid etching process
      was stored under dry conditions at 25 degrees C for 12 hours, and the Ca/P ratio
      approximated to 1.00 accidentally. The initial adhesion, proliferation, and
      differentiation (alkaline phosphatase (ALP) activity and relative mRNA level for
      ALP) of MC3T3-E1 cells on the modified surfaces were significantly promoted (P <
      0.05 and 0.01). These findings show that the 30% phosphoric acid etching process
      for the nanostructured HAP surface can alter the Ca/P ratio effectively and may
      accelerate the initial adhesion, proliferation, and differentiation of MC3T3-E1
      cells. 

PMID- 23862151
TI  - Changes of PBP5 gene expression in enterococcal isolates from renal
      transplantation recipients.
AB  - The aim of the study was to evaluate changes in expression of PBP5 gene
      associated with immunosuppression. A linear locked nucleic acid (LNA) probe was
      used to measure resistance gene expression by the Flow-FISH method. Expression of
      the PBP5 gene measured by Flow-FISH was higher in enterococcal strains isolated
      from renal transplantation (RTx) recipients than in commensal strains.
      Additionally, in contrast to commensal strains in isolates from RTx patients,
      PBP5 gene expression was 17.45% higher in biofilms than in planktonic cells.
      Detailed comparison also showed that cyclosporine seemed to induce higher
      expression of PBP5 as compared to tacrolimus. 

PMID- 23862152
TI  - In silico screening and molecular dynamics simulation of disease-associated nsSNP
      in TYRP1 gene and its structural consequences in OCA3.
AB  - Oculocutaneous albinism type III (OCA3), caused by mutations of TYRP1 gene, is an
      autosomal recessive disorder characterized by reduced biosynthesis of melanin
      pigment in the hair, skin, and eyes. The TYRP1 gene encodes a protein called
      tyrosinase-related protein-1 (Tyrp1). Tyrp1 is involved in maintaining the
      stability of tyrosinase protein and modulating its catalytic activity in
      eumelanin synthesis. Tyrp1 is also involved in maintenance of melanosome
      structure and affects melanocyte proliferation and cell death. In this work we
      implemented computational analysis to filter the most probable mutation that
      might be associated with OCA3. We found R326H and R356Q as most deleterious and
      disease associated by using PolyPhen 2.0, SIFT, PANTHER, I-mutant 3.0, PhD-SNP,
      SNP&GO, Pmut, and Mutpred tools. To understand the atomic arrangement in 3D
      space, the native and mutant (R326H and R356Q) structures were modelled. Finally
      the structural analyses of native and mutant Tyrp1 proteins were investigated
      using molecular dynamics simulation (MDS) approach. MDS results showed more
      flexibility in native Tyrp1 structure. Due to mutation in Tyrp1 protein, it
      became more rigid and might disturb the structural conformation and catalytic
      function of the structure and might also play a significant role in inducing
      OCA3. The results obtained from this study would facilitate wet-lab researches to
      develop a potent drug therapies against OCA3. 

PMID- 23862153
TI  - A polyethylenimine-linoleic acid conjugate for antisense oligonucleotide
      delivery.
AB  - A novel antisense oligonucleotide (ASO) carrier, polyethylenimine conjugated to
      linoleic acid (PEI-LA), was synthesized and evaluated for delivery of LOR-2501 to
      tumor cells. LOR-2501 is an ASO targeting ribonucleotide reductase R1 subunit
      (RRM1). In this study, PEI-LA was synthesized by reacting PEI (Mw ~ 800) with
      linoleoyl chloride. Gel retardation assay showed complete complexation between
      PEI-LA and LOR-2501 at N/P ratio above 8. No significant cytotoxicity was
      observed with these complexes at the tested dosage levels. Interestingly, at N/P
      ratio of >6, levels of cellular uptake of PEI-LA/LOR-2501 were double that of
      PEI/LOR-2501 complexes of the same N/P ratio. PEI-LA/LOR-2501 induced
      downregulation of 64% and 70% of RRM1 at mRNA and protein levels, respectively.
      The highest transfection activity was shown by PEI-LA/LOR-2501 complexes at N/P
      ratio of 10. Finally, using pathway specific inhibitors, clathrin-mediated
      endocytosis was shown to be the principle mechanism of cellular internalization
      of these complexes. In conclusion, PEI-LA is a promising agent for the delivery
      of ASOs and warrants further investigation. 

PMID- 23862154
TI  - A history of the development of Brucella vaccines.
AB  - Brucellosis is a worldwide zoonosis affecting animal and human health. In the
      last several decades, much research has been performed to develop safer Brucella
      vaccines to control the disease mainly in animals. Till now, no effective human
      vaccine is available. The aim of this paper is to review and discuss the
      importance of methodologies used to develop Brucella vaccines in pursuing this
      challenge. 

PMID- 23862155
TI  - Quo vadis radiotherapy? Technological advances and the rising problems in cancer
      management.
AB  - PURPOSE: Despite the latest technological advances in radiotherapy, cancer
      control is still challenging for several tumour sites. The survival rates for the
      most deadly cancers, such as ovarian and pancreatic, have not changed over the
      last decades. The solution to the problem lies in the change of focus: from local
      treatment to systemic therapy. The aim of this paper is to present the current
      status as well as the gaps in radiotherapy and, at the same time, to look into
      potential solutions to improve cancer control and survival. METHODS: The
      currently available advanced radiotherapy treatment techniques have been analysed
      and their cost-effectiveness discussed. The problem of systemic disease
      management was specifically targeted. RESULTS: Clinical studies show limited
      benefit in cancer control from hadron therapy. However, targeted therapies
      together with molecular imaging could improve treatment outcome for several
      tumour sites while controlling the systemic disease. CONCLUSION: The advances in
      photon therapy continue to be competitive with the much more expensive hadron
      therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is
      a need for phase III randomised clinical trials. Furthermore, the success of
      systemic disease management lies in the fusion between radiation oncology
      technology and microbiology.

PMID- 23862156
TI  - Bovine papillomavirus type 2 infection and a series of mesenchymal tumors of the
      urinary bladder in cattle.
AB  - This report describes the histopathology of two hundred and fifty-three
      mesenchymal tumors of the urinary bladder in cattle grazing on lands rich in
      bracken fern. Approximately 80% were hemangiomas and angiosarcomas. Hemangioma
      (capillary, cavernous, and large vessels) was the most frequent mesenchymal tumor
      and was more common than angiosarcoma. Although the appearance of endothelial
      cells can vary remarkably, epithelioid angiosarcomas, often containing
      multinucleated cells, were the most frequent malignant vascular tumors.
      Hemangiopericytoma and tumors of muscle and soft connective tissue origin, alone
      and/or in association with tumor-like lesions, were less frequently seen.
      Furthermore, forty-five cases of intravascular papillary endothelial hyperplasia
      (IPEH), a lesion not previously reported in the urinary bladder of cattle, were
      also described. Bovine papillomavirus type-2 DNA was amplified in tumor samples.
      Forty vascular tumors were investigated by dual-labeling immunofluorescence, and,
      for the first time, a coexpression of E5 and platelet-derived growth factor beta
      receptor (PDGF beta R) was shown to occur. The results show that the BPV-2 E5
      oncoprotein binds to the activated form of the PDGF beta receptor thus playing an
      important role in mesenchymal as well as epithelial carcinogenesis of the urinary
      bladder. Furthermore, these findings demonstrate that BPV-2 infects both
      epithelial and mesenchymal cells. 

PMID- 23862157
TI  - Antioxidant and renoprotective effects of Spirogyra neglecta (Hassall) Kutzing
      extract in experimental type 2 diabetic rats.
AB  - Spirogyra neglecta extract (SNE) has shown antihyperglycemia and
      antihyperlipidemia in type 2 diabetic mellitus (T2DM) rats. This study
      investigated the antioxidant and renoprotective effects of SNE in T2DM rats
      induced by high-fat diet with low-single dose streptozotocin. T2DM rats were fed
      daily with SNE (0.25, 0.5, and 1 g/kg BW) for 12 weeks. Renal morphology,
      malondialdehyde levels, qPCR, and western blotting were analyzed. Renal cortical
      slices were used to determine renal transport of organic anions, which are
      estrone sulfate and para-aminohippurate, mediated through organic anion
      transporter 3-Oat3. Insulin and PKCzeta were known to activate Oat3 function
      while it was inhibited by PKCalpha. Compared to T2DM, plasma glucose,
      triglyceride, insulin resistance, renal morphology, and malondialdehyde levels
      were significantly improved by SNE supplementation. Reduced glutathione
      peroxidase and nuclear factor kappaB expressions were related to antioxidant
      effect of SNE. Oat3 mRNA and protein were not different among groups, but insulin
      stimulated rOat3 followed by anion uptakes was abolished in T2DM. This was
      restored in the slices from SNE treatment. The mechanism of SNE-improved Oat3 was
      associated with PKCalpha and PKCzeta expressions and activities. These findings
      indicate that SNE has beneficial effects on renal transport through antioxidant
      enzymes and PKCs in T2DM rats.

PMID- 23862158
TI  - The occurrence of two species of Entomophthorales (Entomophthoromycota),
      pathogens of Sitobion avenae and Myzus persicae (Hemiptera: Aphididae), in
      Tunisia.
AB  - The natural occurrence of entomophthoralean fungi pathogenic towards aphids on
      cereal and potato crops was investigated in the years 2009, 2010, and 2011.
      Infected aphids were sampled in three bioclimatic zones in Tunisia (Beja, Cap
      bon, and Kairouan) and fungal species were determined based on morphological
      characters such as shape, size, and number of nuclei in the primary conidia.
      Polymerase Chain Reaction (PCR) on the internal transcribed spacer 1 region
      (ITS1) was used to verify morphological determination. Both methods gave
      consistent results and we documented for the first time the natural occurrence of
      two fungal species from the order Entomophthorales (phylum Entomophthoromycota),
      Pandora neoaphidis and Entomophthora planchoniana. Both fungi were recorded on
      the aphid species Sitobion avenae and Myzus persicae on barley ears and potato
      leaves, respectively. Moreover, natural mixed infections by both species (P.
      neoaphidis and E. planchoniana) were documented on the target aphids. This
      investigation provides basic information of entomopathogenic fungi infecting
      economically important aphids in Tunisia. 

PMID- 23862159
TI  - Effects of fermentation temperature and aeration on production of natural isoamyl
      acetate by Williopsis saturnus var. saturnus.
AB  - Isoamyl acetate is a natural flavour ester, widely used as a source of banana
      flavour by the food industry. Williopsis saturnus var. saturnus is a yeast which
      can produce isoamyl acetate by esterification of amyl alcohols with acetyl
      coenzyme A via fermentation. The evaluation of this kind of production as an
      alternative way to obtain natural banana flavour could be possible, if the levels
      produced were high enough to make a commercial product. In this study, the
      effects of temperature (15 degrees C and 25 degrees C) and aeration (aerobic,
      semiaerobic, and anaerobic) on the production of isoamyl acetate by Williopsis
      saturnus var. saturnus from sugar beet molasses were examined. According to the
      results obtained, isoamyl acetate production rate and specific productivity were
      higher at 25 degrees C than at 15 degrees C and at semiaerobic condition than
      aerobic and anaerobic conditions. Williopsis saturnus var. saturnus showed a
      production rate of 0.703 mg (-1) h(-1) and a specific productivity of 0.0297 mg
      L(-1) cell(-1) h(-1) isoamyl acetate with semiaerobic condition at 25 degrees C.
      The maximum amount of isoamyl acetate reached with these conditions was 118 mg/L.

PMID- 23862160
TI  - Assessment of respiration-induced motion and its impact on treatment outcome for
      lung cancer.
AB  - This study presented the analysis of free-breathing lung tumor motion
      characteristics using GE 4DCT and Varian RPM systems. Tumor respiratory movement
      was found to be associated with GTV size, the superior-inferior tumor location in
      the lung, and the attachment degree to rigid structure (e.g., chest wall,
      vertebrae, or mediastinum), with tumor location being the most important factor
      among the other two. Improved outcomes in survival and local control of 43 lung
      cancer patients were also reported. Consideration of respiration-induced motion
      based on 4DCT for lung cancer yields individualized margin and more accurate and
      safe target coverage and thus can potentially improve treatment outcome. 

PMID- 23862161
TI  - The golden ratio of gait harmony: repetitive proportions of repetitive gait
      phases.
AB  - In nature, many physical and biological systems have structures showing harmonic
      properties. Some of them were found related to the irrational number phi known as
      the golden ratio that has important symmetric and harmonic properties. In this
      study, the spatiotemporal gait parameters of 25 healthy subjects were analyzed
      using a stereophotogrammetric system with 25 retroreflective markers located on
      their skin. The proportions of gait phases were compared with phi, the value of
      which is about 1.6180. The ratio between the entire gait cycle and stance phase
      resulted in 1.620 +/- 0.058, that between stance and the swing phase was 1.629 +/
      0.173, and that between swing and the double support phase was 1.684 +/- 0.357.
      All these ratios did not differ significantly from each other (F = 0.870, P =
      0.422, repeated measure analysis of variance) or from phi (P = 0.670, 0.820,
      0.422, resp., t-tests). The repetitive gait phases of physiological walking were
      found in turn in repetitive proportions with each other, revealing an intrinsic
      harmonic structure. Harmony could be the key for facilitating the control of
      repetitive walking. Harmony is a powerful unifying factor between seemingly
      disparate fields of nature, including human gait.

PMID- 23862162
TI  - Lipoprotein(a) serum levels in diabetic patients with retinopathy.
AB  - BACKGROUND: Atherogenic lipoproteins, such as total cholesterol, LDL cholesterol,
      oxidized low density lipoprotein, and triglycerides, are associated with
      progression of retinopathy. Aim. To evaluate the relationship between
      lipoprotein(a) and retinopathy in patients with type 2 diabetes mellitus.
      MATERIALS AND METHODS: We enrolled 145 diabetic consecutive patients (82 females,
      63 males; mean age 66.8 +/- 12 years, mean duration of diabetes 9.4 +/- 6.8
      years). Presence and severity of retinopathy were evaluated. Serum lipid profile,
      including Lp(a) level, was assessed. RESULTS: High Lp(a) levels have been
      observed in 54 (78.3%) subjects and normal levels in 13 (18.85%) subjects as
      regards diabetic patients with retinopathy. Lp(a) levels were high in 15 subjects
      (21.75%) and normal in 63 subjects (91.35%) as regards patients without
      retinopathy. CONCLUSIONS: Lp(a) levels are increased in a significant percentage
      of patients with retinopathy compared to diabetic patients without retinopathy.
      The impact of Lp(a) levels on diabetic retinopathy needs to be further
      investigated.

PMID- 23862165
TI  - Routine duodenal biopsies to diagnose celiac disease.

PMID- 23862163
TI  - Advanced MR imaging of gliomas: an update.
AB  - Recent advances in the treatment of cerebral gliomas have increased the demands
      on noninvasive neuroimaging for the diagnosis, therapeutic planning, tumor
      monitoring, and patient outcome prediction. In the meantime, improved magnetic
      resonance (MR) imaging techniques have shown much potentials in evaluating the
      key pathological features of the gliomas, including cellularity, invasiveness,
      mitotic activity, angiogenesis, and necrosis, hence, further shedding light on
      glioma grading before treatment. In this paper, an update of advanced MR imaging
      techniques is reviewed, and their potential roles as biomarkers of tumor grading
      are discussed. 

PMID- 23862166
TI  - Intraductal oncocytic papillary neoplasm: a rare pancreatic mass.

PMID- 23862164
TI  - Inflammation and oxidative stress in diabetic nephropathy: new insights on its
      inhibition as new therapeutic targets.
AB  - Diabetes and insulin resistance can greatly increase microvascular complications
      of diabetes including diabetic nephropathy (DN). Hyperglycemic control in
      diabetes is key to preventing the development and progression of DN. However, it
      is clinically very difficult to achieve normal glucose control in individual
      diabetic patients. Many factors are known to contribute to the development of DN.
      These include diet, age, lifestyle, or obesity. Further, inflammatory- or
      oxidative-stress-induced basis for DN has been gaining interest. Although anti
      inflammatory or antioxidant drugs can show benefits in rodent models of DN,
      negative evidence from large clinical studies indicates that more effective anti
      inflammatory and antioxidant drugs need to be studied to clear this question. In
      addition, our recent report showed that potential endogenous protective factors
      could decrease inflammation and oxidative stress, showing great promise for the
      treatment of DN. 

PMID- 23862167
TI  - Chilaiditi's syndrome with interposed sigmoid colon mimicking traumatic
      pneumoperitoneum.

PMID- 23862168
TI  - HFE mutations in Caucasian participants of the Hemochromatosis and Iron Overload
      Screening study with serum ferritin level <1000 ug/L.
AB  - BACKGROUND: Many patients referred for an elevated serum ferritin level <1000
      ug/L are advised that they likely have iron overload and hemochromatosis. AIMS:
      To determine the prevalence of HFE mutations in the hemochromatosis gene for 11
      serum ferritin concentration intervals from 200 ug/L to 1000 ug/L in Caucasian
      participants in a primary care, population-based study. METHODS: The
      Hemochromatosis and Iron Overload Screening study screened 99,711 participants
      for serum ferritin levels, transferrin saturation and genetic testing for the
      C282Y and H63D mutations of the HFE gene. This analysis was confined to 17,160
      male and 27,465 female Caucasian participants because the HFE C282Y mutation is
      rare in other races. Post-test likelihood was calculated for prediction of C282Y
      homozygosity from a ferritin interval. A subgroup analysis was performed in
      participants with both an elevated serum ferritin level and transferrin
      saturation. RESULTS: There were 3359 male and 2416 female participants with an
      elevated serum ferritin level (200 ug/L to 1000 ug/L for women, 300 ug/L to 1000
      ug/L for men). There were 69 male (2.1%) and 87 female (3.6%) C282Y homozygotes,
      and the probability of being a homozygote increased as the ferritin level
      increased. Post-test likelihood values were 0.3% to 16% in men and 0.3% to 30.4%
      in women. CONCLUSIONS: Iron loading HFE mutations are unlikely to be the most
      common cause of an elevated serum ferritin level in patients with mild
      hyperferritinemia. Patients should be advised that there are many causes of an
      elevated serum ferritin level including iron overload.

PMID- 23862169
TI  - In a 'real-world', clinic-based community setting, sorafenib dose of 400 mg/day
      is as effective as standard dose of 800 mg/day in patients with advanced
      hepatocellular carcimona, with better tolerance and similar survival.
AB  - BACKGROUND: Sorafenib, an oral multityrosine kinase inhibitor, has been approved
      for treatment of unresectable hepatocellular carcinoma (HCC). British Columbia
      (BC) was the first province in Canada to provide drug coverage for sorafenib.
      OBJECTIVE: To review the BC experience with sorafenib to assess its effectiveness
      and tolerance in a 'real-world' clinical setting. METHODS: A retrospective clinic
      chart review identified 99 patients referred to the BC Cancer Agency from 2008 to
      2010 with a diagnosis of HCC who qualified for treatment with sorafenib. RESULTS:
      Therapy with sorafenib was initiated and continued at a reduced dosage of 400
      mg/day in 66 of 99 patients, with 22 patients requiring further dose reduction.
      Full- and reduced-dose group patients had similar baseline characteristics,
      except for a higher proportion of female patients (P=0.02) and individuals with
      alcoholic liver disease (P=0.04) in the full-dose group. The incidence of any
      grade of adverse effects was higher in the full-dose group (94% versus 77% in the
      reduced-dose group; P=0.04). Dose reduction rates were significantly higher in
      the full-dose group, occurring in 66% versus 24% of reduced-dose group patients
      (P=0.001). The overall survival rates were similar between the two groups: 7.8
      months versus 7.1 months in full- versus reduced-dose groups (P=0.14), as were
      radiological progression rates and alpha-fetoprotein levels. CONCLUSIONS: In a
      review of 99 patients in a 'real-world' community setting, a sorafenib dose of
      400 mg/day was better tolerated and had similar efficacy compared with a
      sorafenib dose of 800 mg/day with respect to survival and outcomes.

PMID- 23862170
TI  - Prolonged treatment duration is required for successful Helicobacter pylori
      eradication with proton pump inhibitor triple therapy in Canada.
AB  - BACKGROUND: Traditional seven-day proton pump inhibitor triple therapy for
      Helicobacter pylori eradication has recently shown disappointing results outside
      of Canada. Prolonging therapy may be associated with poorer compliance and,
      hence, may not have a better outcome in a real-world setting. OBJECTIVE: To
      compare the outcomes of seven- and 14-day triple therapy for first-line treatment
      of H pylori infection in an effectiveness setting in Canada. METHODS: A total of
      314 consecutive treatment-naive, adult H pylori-infected patients were allocated
      to either a seven- or 14-day triple therapy regimen, with a subgroup of 172
      consecutive patients quasi-randomized to treatment according to date of visit.
      Eradication was confirmed using either urea breath test or gastric biopsies.
      Analysis was by intention to treat. RESULTS: Eradication was achieved in a higher
      proportion of patients who underwent 14-day versus seven-day treatment regimens
      (overall: 85% versus 70% [P<=0.001]; subgroup: 83% versus 64% [P<=0.01]).
      Although successful eradication was also associated with older age and a
      diagnosis of ulcer disease, multivariate analysis revealed only longer treatment
      duration and lack of yogurt ingestion as independent predictors of successful
      eradication. There was a trend toward reduced success in the latter years of the
      study. Side effects were similar in both groups and were not prevented by yogurt
      ingestion. CONCLUSIONS: The currently recommended duration of proton pump
      inhibitor triple therapy in Canada should be increased from seven to 14 days, the
      latter having achieved an excellent result in this particular real-world setting.
      Yogurt added no benefit. Further study is required to compare 10-day with 14-day
      treatment regimens.

PMID- 23862171
TI  - Use of the alpha glucosidase inhibitor acarbose in patients with 'Middleton
      syndrome': normal gastric anatomy but with accelerated gastric emptying causing
      postprandial reactive hypoglycemia and diarrhea.
AB  - Postprandial reactive hypoglycemia, early satiety and diarrhea are well
      recognized side effects following full or partial gastrectomy or gastric bypass.
      It has only recently been realized, however, that patients with normal gastric
      anatomy may experience similar symptoms and signs due to primary accelerated
      gastric emptying (Middleton syndrome). In previous case studies, patients
      responded well to the use of dietary modification (frequent small-volume meals)
      alone. The authors describe two patients with this syndrome who continued to
      experience symptoms of reactive postprandial hypoglycemia despite dietary
      intervention but became asymptomatic following the addition of the alpha
      glucosidase inhibitor acarbose. 

PMID- 23862172
TI  - Detection of adult celiac disease with duodenal screening biopsies over a 30-year
      period.
AB  - BACKGROUND: Serological studies suggest that celiac disease may be present in
      approximately 0.5% to 1% of the North American population. Screening data based
      on small intestinal biopsy performed during routine endoscopic evaluations are
      not available. METHODS: Patients referred between January 1982 and December 2011
      for evaluation of gastrointestinal symptoms and requiring elective investigative
      upper endoscopic evaluation underwent duodenal biopsies to determine whether
      changes of adult celiac disease were present. RESULTS: A total of 9665 patients,
      including 4008 (41.5%) males and 5657 (68.5%) females, underwent elective
      endoscopies and duodenal biopsies. Of these, 234 (2.4%) exhibited changes of
      celiac disease including 73 males (1.8%) and 161 females (2.8%). During the first
      20 years, the number of biopsy-positive patients in five-year intervals
      progressively decreased and, subsequently, during the next 10 years, the number
      progressively increased. CONCLUSIONS: Celiac disease is far more common in
      specialist practice than has been suggested in the evaluation of healthy
      populations using serological screening studies. Endoscopic duodenal biopsy is an
      important method of identifying underlying celiac disease and should be routinely
      considered in all patients undergoing an elective endoscopic evaluation.
      Noninherited factors, possibly environmental, may play a role in the appearance
      of biopsy-defined celiac disease and alter detection over time.

PMID- 23862173
TI  - Natural history and long-term outcomes of patients treated for early stage
      colorectal cancer.
AB  - BACKGROUND: The long-term natural history of early stage colon cancer and the
      outcome of long-term colonoscopic surveillance in routine specialist clinical
      practice after removal of the incident cancers have not been fully defined. In
      the present long-term evaluation up to 25 years, metachronous neoplasia,
      including both advanced adenomas and carcinomas, was defined. METHODS: All early
      stage colorectal cancer patients evaluated consecutively from a single clinical
      practice underwent follow-up colonoscopic evaluations after removal of the
      incident cancer and clearing of neoplastic disease. Colonoscopic surveillance was
      planned for two phases - initially on an annual basis for five years, followed by
      continued surveillance every three years up to 25 years with removal of any
      metachronous neoplastic lesion. RESULTS: A total of 128 patients (66 men and 62
      women) with 129 incident early stage colorectal cancers were evaluated. Virtually
      all patients were symptomatic, usually with clinical evidence of blood loss.
      Incident early cancers were located throughout the colon, especially in the
      rectosigmoid, and showed no pathological evidence of nodal or other metastases.
      All patients evaluated during the first five years did not experience recurrent
      disease or have metachronous cancer detected. After five years, a total of 94
      patients were evaluated up to 25 years; six of these patients were found to have
      seven metachronous colon cancers. All developed cancer more than seven years
      after removal of the incident colorectal cancer, including six asymptomatic
      adenocarcinomas, of which only one had evidence of single node involvement.
      Another patient in this cohort developed a poorly differentiated neuroendocrine
      carcinoma of the colon. In addition, 45% of patients had a total of 217 adenomas
      removed, including 11% of patients with 33 advanced adenomas. Among 14 patients
      with advanced adenomas, seven (50%) developed >=1 late metachronous cancers.
      CONCLUSIONS: Following removal of an incident symptomatic early stage colorectal
      cancer, the risk of later metachronous neoplasia persists for an extended period
      more than five years after removal of the incident colorectal cancer. Moreover,
      risk for late metachronous cancer appears to be predicted by the presence of
      multiple adenomas or advanced adenomas; most metachronous cancers in this cohort
      were detected using colonoscopy before onset of symptoms and at an early stage.

PMID- 23862174
TI  - Pretreatment resistance to hepatitis C virus protease inhibitors
      boceprevir/telaprevir in hepatitis C virus subgenotype 1a-infected patients from
      Manitoba.
AB  - BACKGROUND: Traditional therapy with pegylated interferon and ribavirin combined
      with the new protease inhibitors boceprevir or telaprevir has demonstrated
      improved outcomes in hepatitis C virus (HCV)-infected patients. Prevalence data
      regarding pre-existing drug-resistant variants to these two new virus inhibitors
      in the Canadian population are not available. OBJECTIVE: To detect pre-existing
      mutations conferring resistance to boceprevir and/or telaprevir in Canadian
      patients infected with HCV genotype 1a. METHODS: Resistance-associated mutations
      (RAMs) were evaluated in 85 patients infected with HCV genotype 1a who had not
      yet received antiviral therapy. The NS3 protease gene was sequenced and common
      RAMs were identified based on a recently published list. RESULTS: The overall
      prevalence of pre-existing RAMs to boceprevir and telaprevir was higher compared
      with other similar studies. All of the observed RAMs were associated with a low
      level of resistance. A surprisingly high proportion of patients had the V55A RAM
      (10.6%). None of the mutations associated with a high level of resistance were
      observed. The simultaneous presence of two low-level resistance mutations (V36L
      and V55A) was observed in only one patient. Three other patients had both T54S
      RAM and V55I mutations, which may require a higher concentration of the protease
      drugs. The prevalence of various mutations in Aboriginal Canadian patients was
      higher (37.5%) compared with Caucasians (16.39%) (P=0.038). CONCLUSIONS: The
      present study was the first to investigate pre-existing drug resistance to
      boceprevir/telaprevir in Canadian HCV-infected patients. A relatively high
      proportion of untreated HCV genotype 1a patients in Manitoba harbour low-level
      RAMs, especially patients of Aboriginal descent, which may contribute to an
      increased risk of treatment failure.

PMID- 23862176
TI  - O2 plasma-functionalized SWCNTs and PEDOT/PSS composite film assembled by
      dielectrophoresis for ultrasensitive trimethylamine gas sensor.
AB  - A novel gas sensor based on composite films of poly(3,4
      ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) and single-walled
      carbon nanotubes (SWCNTs) was fabricated for the detection of fishy
      trimethylamine (TMA) vapor. The SWCNTs were functionalized by O2 plasma treatment
      to improve their solubility in the polymeric matrix, and alternative current
      dielectrophoresis was utilized for the first time to assemble the PEDOT/PSS
      SWCNTs composite film to enhance the response to TMA molecules. The high
      resolution transmission electron microscopy (HR-TEM) images showed that the
      SWCNTs maintained their bulk structure after O2 plasma functionalization. The
      scanning electron microscopy (SEM) images of the composite film showed that the
      oxidized SWCNTs were orderly arranged and uniformly dispersed into the polymer by
      dielectrophoresis. Compositional analyses of SWCNTs by X-ray photoelectron
      spectroscopy (XPS) suggested that O2 plasma functionalization could remove
      amorphous carbon from the nanotube surface and introduce more hydrophilic oxygen
      containing groups, leading to the improvement of SWCNTs solubility in the
      polymeric matrix. Gas sensitivities of the composite films largely relied on the
      treatment conditions. Compared to the raw or acid-treated SWCNTs-doped composite
      films, the film doped with SWCNTs modified by O2 plasma at 30 W for 3 min
      exhibited the most sensitive and stable response characteristics to ppb-level TMA
      gas. 

PMID- 23862177
TI  - Influence of achiral units with gem-dimethyl substituents on the helical
      character of aliphatic oligourea foldamers.
AB  - The structures of various urea oligomers incorporating one or two central achiral
      1,2-diamino-1,1-dimethylethane (DADME) units have been investigated in solution
      and in the crystalline state. These diamine monomers are analogous to the achiral
      helicogenic amino acid Aib (alpha-aminoisobutyric acid). Oligomers were found to
      fold into helical conformations with DADME units inducing local deviations from
      the canonical helix geometry of urea foldamers. 

PMID- 23862175
TI  - Diagnosis and management of the overlap syndromes of autoimmune hepatitis.
AB  - BACKGROUND: Autoimmune hepatitis may have cholestatic features that are outside
      the classical phenotype and that resemble findings in other immune-mediated liver
      diseases. These cholestatic phenotypes have been designated 'overlap syndromes'.
      OBJECTIVES: To recognize the overlap syndromes in adults and manage them
      appropriately. METHODS: The MEDLINE database was reviewed for published
      experiences from 1984 to 2013. RESULTS: Patients with autoimmune hepatitis may
      exhibit features of primary biliary cirrhosis (7% to 13%), primary sclerosing
      cholangitis (6% to 11%) or a cholestatic syndrome without other diagnostic
      features (5% to 11%). These mixed phenotypes may represent classical autoimmune
      hepatitis with atypical features, transition states in the evolution of classical
      cholestatic syndromes, concurrent separate diseases or pathogenically distinct
      disorders. The 'Paris criteria' have been endorsed for the diagnosis of the
      overlap syndrome with primary biliary cirrhosis, and treatment with conventional
      immunosuppressive therapy alone or in combination with low-dose ursodeoxycholic
      acid can be guided by the serum alkaline phosphatase level. The overlap syndrome
      with primary sclerosing cholangitis or with cholestasis without diagnostic
      features is commonly treated with immunosuppressive therapy and ursodeoxycholic
      acid. Responses are variable and commonly incomplete (20% to 100% improvement)
      depending on the degree of cholestasis. DISCUSSION: The overlap syndromes are
      clinical descriptions rather than pathological entities, and the dominant
      component of the disease determines its designation and therapy. Cholestatic
      findings in autoimmune hepatitis influence the response to immunosuppressive
      therapy. CONCLUSION: The overlap syndromes must be considered in patients with
      autoimmune hepatitis and cholestatic findings, concurrent inflammatory bowel
      disease or steroid-refractory disease.

PMID- 23862178
TI  - Photochirogenesis with mutant human serum albumins: enantiodifferentiating
      photocyclodimerization of 2-anthracenecarboxylate.
AB  - Mutant human serum albumins accelerated the photocyclodimerization of 2
      anthracenecarboxylate to afford chiral cyclodimers in 75-85% enantiomeric
      excesses, revealing that the mutations to impair non-productive sites 1 and/or 2
      enhanced the substrate binding to site 3 without seriously damaging its
      inherently high photochirogenic ability. 

PMID- 23862179
TI  - A facile "bottom-up" approach to prepare free-standing nano-films based on
      manganese coordination clusters.
AB  - We present herein a novel method to prepare free-standing Dried Foam Films (DFFs)
      whereby individual polynuclear manganese complexes cover quantitatively the holes
      of micro-grids; the fabricated, homogeneous films have a cross-sectional
      thickness of only ca. 5 nm and are characterised by high mechanical stability.

PMID- 23862180
TI  - Flexibility of ZIF-8 materials studied using 129Xe NMR.
AB  - Structural changes in a porous hybrid inorganic-organic ZIF-8 compound have been
      explored using hyperpolarized (129)Xe NMR of adsorbed xenon at various
      temperatures. Upon xenon adsorption at low temperature, the organic linkers
      undergo a reorientation leading to a stepwise increase in xenon adsorption and in
      chemical shift. 

PMID- 23862181
TI  - Ligand effects of NHC-iridium catalysts for signal amplification by reversible
      exchange (SABRE).
AB  - SABRE hyperpolarizes substrates by polarization transfer from para-hydrogen in a
      metal complex. We have measured the signal enhancement of pyridine and its
      exchange rate in various [Ir(NHC)(Py)3(H)2](+) complexes to gain insight into
      their dependence on the N-Heterocyclic Carbene (NHC) ligand's steric and
      electronic properties. 

PMID- 23862182
TI  - Understanding the topography effects on competitive adsorption on a nanosized
      anatase crystal: a molecular dynamics study.
AB  - Using Molecular Mechanics and Molecular Dynamics methods, we investigated at the
      atomistic level the topography effects both on physisorption on different
      crystalline planes of TiO2 anatase and on the competitive adsorption when three
      different crystallographic faces were simultaneously present in an idealized
      nanosized crystal interacting with a simple heteroaromatic molecule
      experimentally used in sunlight-induced photosynthetic reaction. 

PMID- 23862183
TI  - Significance for the sake of significance: the relevance of statistical data.

PMID- 23862184
TI  - Postural instability after acute ischemic stroke.

PMID- 23862185
TI  - Galantamine for vascular cognitive impairment.
AB  - BACKGROUND: Vascular dementia represents the second most common type of dementia
      after that caused by Alzheimer's disease. Particularly in older patients, the
      combination of vascular dementia and Alzheimer's disease is common and is
      referred to as mixed dementia. The classification of vascular dementia broadly
      follows three clinico-pathological processes: multi-infarct dementia, single
      strategic infarct dementia and subcortical dementia. Not all patients fulfil
      strict criteria for dementia and may be significantly cognitively impaired
      without memory loss and the term vascular cognitive impairment is more useful.
      Currently, no established standard treatment for vascular cognitive impairment
      exists. Reductions in acetylcholine and acetyltransferase activity are common to
      both Alzheimer's disease and vascular cognitive impairment raising the
      possibility that cholinesterase inhibitors such as galantamine may be beneficial
      for the latter. OBJECTIVES: To assess the efficacy of galantamine in the
      treatment of people with vascular cognitive impairment or vascular dementia or
      mixed dementia. SEARCH METHODS: The trials were identified from a search of
      ALOIS: the Cochrane Dementia and Cognitive Improvement Group's Specialized
      Register on 12 January 2013. The register contains information on trials
      identified from frequent searches of a number of major healthcare and medical
      databases (MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS) as well as from a number
      of international and national trial registries and grey literature sources. The
      terms used were: galantamine, galanthamine, Reminyl, Razadyne, Nival in.
      SELECTION CRITERIA: All unconfounded randomised double-blind trials comparing
      galantamine with placebo were eligible for inclusion. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted the data from included
      studies. MAIN RESULTS: Two trials, 1378 participants, employing randomised,
      double-blind, parallel-group methodology were included. Both trials were of six
      months duration and were testing a galantamine dose of 16-24 mg/day in two
      divided doses. Both trials had an overall low risk of bias.The GAL-INT-6 trial
      included 592 patients with vascular dementia diagnosed according to recognised
      criteria and patients with Alzheimer's disease and coincidental radiographic
      findings of cerebrovascular disease. Limited outcome data were reported for the
      subgroup data with vascular dementia. In the whole trial population,
      statistically significant treatment effects in favour of galantamine compared
      with placebo in cognition (ADAS-cog,mean difference (MD) -2.29, 95%confidence
      interval (CI) -3.46 to -1.12, P = 0.0001), activities of daily living (DAD, MD
      4.10, 95% CI 1.25 to 6.95, P = 0.005) and behaviour (NPI, MD -2.06, 95% CI -4.09
      to -0.03,P = 0.05 ) were noted. Significantly higher numbers of patients dropped
      out, (102/396 galantamine, 33/196 placebo odds ratio (OR)1.71, 95% CL 1.11 to
      2.65, P = 0.02) and withdrew due to an adverse event from the group treated with
      galantamine compared with the placebo group (79/396 galantamine, 16/196 placebo,
      OR 2.80, 95% CI 1.59 to 4.95, P =0.0004).Data were also included from a second
      larger trial (GAL-INT-26) involving 788 patients with vascular dementia diagnosed
      using standard criteria. Statistically significant benefits favouring galantamine
      over placebo in assessments of cognition (ADAS-cog, MD -1.50, 95% CI -2.39 to 
      0.61, P = 0.0009), and favouring placebo compared with galantamine for behaviour
      (NPI, MD 1.80, 95% CI0.29 to 3.31, P = 0.02) are recorded. Significantly higher
      numbers of patients dropped out from the group treated with galantamine compared
      with the placebo group (50/396 galantamine, 25/390 placebo OR 2.11, 95% CL 1.28
      to 3.49, P = 0.004). AUTHORS' CONCLUSIONS: Limited data were available when
      considering the impact of galantamine on vascular dementia or vascular cognitive
      impairment. The data available suggest some advantage over placebo in the areas
      of cognition and global clinical state. In both included trials galantamine
      produced higher rates of gastrointestinal side-effects. More studies are needed
      before firm conclusions can be drawn.

PMID- 23862186
TI  - 'Scared Straight' and other juvenile awareness programs for preventing juvenile
      delinquency.
AB  - BACKGROUND: 'Scared Straight' and other similar programs involve organized visits
      to prison by juvenile delinquents or children at risk for criminal behavior.
      Programs are designed to deter participants from future offending through first
      hand observation of prison life and interaction with adult inmates. These
      programs remain in use despite research questioning their effectiveness. This is
      an update of a 2002 review. OBJECTIVES: To assess the effects of programs
      comprising organized visits to prisons by juvenile delinquents (officially
      adjudicated, that is, convicted by a juvenile court) or pre-delinquents (children
      in trouble but not officially adjudicated as delinquents), aimed at deterring
      them from delinquency. SEARCH METHODS: To update this review, we searched 22
      electronic databases, including CENTRAL, MEDLINE, PsycINFO, and Criminal Justice
      Abstracts, in December 2011. In addition, we searched clinical trials registries,
      consulted experts, conducted Google Scholar searches,and followed up on all
      relevant citations. SELECTION CRITERIA: We included studies that tested programs
      involving the organized visits of delinquents or children at risk for delinquency
      to penal institutions such as prisons or re formatives. Studies that had
      overlapping samples of juvenile and young adults (for example, ages 14 to 20
      years) were included. We only considered studies that assigned participants to
      conditions randomly or quasi-randomly (that is,by odd/even assignment to
      conditions). Each study had to have a no-treatment control condition and at least
      one outcome measure of 'post-visit' criminal behavior. DATA COLLECTION AND
      ANALYSIS: The search methods for the original review generated 487 citations,
      most of which had abstracts. The lead review author screened these citations,
      determining that 30 were evaluation reports. Two review authors independently
      examined these citations and agreed that 11 were potential randomized trials. All
      reports were obtained. Upon inspection of the full-text reports, two review
      authors independently agreed to exclude two studies, resulting in nine randomized
      trials. The lead review author extracted data from each of the nine study reports
      using a specially designed instrument. In cases in which outcome information was
      missing from the original reports, we made attempts via correspondence to
      retrieve the data for the analysis from the original investigators. Outcome data
      were independently checked by a second review author (CTP).In this review, we
      report the results of each of the nine trials narratively.We conducted two meta
      analyses of seven studies that provided post intervention offending rates using
      official data. Information from other sources (for example, self-report) was
      either missing from some studies or critical information was omitted (for
      example, standard deviations).We examined the immediate post-treatment
      effects(that is, 'first-effects') by computing odds ratios (OR) for data on
      proportions of each group re offending, and assumed both fixed-effect and random
      effects models in our analyses. MAIN RESULTS: We have included nine studies in
      this review. All were part of the original systematic review; no new trials
      meeting eligibility criteria were identified through our updated searches. The
      studies were conducted in eight different states of the USA, during the years
      1967 to 1992. Nearly 1000 (946) juveniles or young adults of different races
      participated, almost all males. The average age of the participants in each study
      ranged from 15 to 17 years.Meta-analyses of seven studies show the intervention
      to be more harmful than doing nothing. The OR (fixed-effect) for effects on first
      post-treatment effect on officially measured criminal behavior indicated a
      negative program effect (OR 1.68, 95% confidence interval (CI) 1.20 to 2.36) and
      nearly identical regardless of the meta-analytic strategy (random-effectsOR 1.72,
      95%CI 1.13 to 2.62).Sensitivity analyses (random-effects) showed the findings
      were robust even when removing one study with an inadequate randomization
      strategy (OR 1.47, 95% CI 1.03 to 2.11), or when removing one study with high
      attrition (OR 1.96, 95% CI 1.25 to 3.08), or both(OR 1.68, 95% CI 1.10 to 2.58).
      AUTHORS' CONCLUSIONS: We conclude that programs such as 'cared Straight' increase
      delinquency relative to doing nothing at all to similar youths. Given these
      results, we cannot recommend this program as a crime prevention strategy.
      Agencies that permit such programs, therefore, must rigorously evaluate them, to
      ensure that they do not cause more harm than good to the very citizens they
      pledge to protect.

PMID- 23862187
TI  - [Dried plums improve bone density].

PMID- 23862188
TI  - [Bisphosphonates: less colon carcinomas].

PMID- 23862189
TI  - [Dependence on denosumab for peripheral fracture reduction and on bone density of
      the femur].

PMID- 23862190
TI  - Reply to D. Milne et al.

PMID- 23862191
TI  - Reply to A. Azad et al.

PMID- 23862192
TI  - Reply to G. Piessen et al.

PMID- 23862193
TI  - [History of medical oncology].

PMID- 23862194
TI  - [Cancer surgery in 2025].

PMID- 23862195
TI  - [To restore trust in drugs].

PMID- 23862196
TI  - Abstracts of the STI & AIDS World Congress. July 14-17, 2013. Vienna, Austria.

PMID- 23862197
TI  - [A posteriori biological demonstration of the concept of hormone-radiotherapy
      combination in cancer of the prostate].

PMID- 23862198
TI  - Authors' reply.

PMID- 23862199
TI  - Ten proven motivation principles.

PMID- 23862200
TI  - Pancreatic heterotopia of the small intestine: two case reports.
AB  - The presence of heterotopic pancreas is unusual with an estimated incidence of
      0.2% of upper abdominal operations. Heterotopic pancreas occurs predominantly in
      the stomach, duodenum and proximal jejunum. Isolated pancreatic heterotopia of
      the ileum is very rare and is usually found in a Meckel's diverticulum. In most
      cases, these heterotopias are asymptomatic and are only incidentally detected
      upon pathological examination or autopsy. In this paper, the authors report two
      cases of pancreatic heterotopia involving, respectively, the duodenum and ileum
      that were fortuitously discovered on a surgical specimen and during laparotomy
      for unrelated causes.

PMID- 23862201
TI  - Our concept of heart attack is changing.  Doctors are rethinking how heart
      attacks are defined and diagnosed.

PMID- 23862202
TI  - Ask the doctors. I had a small heart attack last year when I was undergoing an
      operation to remove part of my colon. I am doing fine in that regard, but now I
      need cataract surgery, and my ophthalmologist has sent me to my internist for
      "clearance" before surgery. Does this mean my risk for another heart attack is
      high?

PMID- 23862203
TI  - Ask the doctors.  I recently had a drug-eluting stent placed in one of my
      coronary arteries after an episode of severe chest pain.  My doctor told me I had
      to take Plavix every day.  Now I feel perfectly fine-except for my right hip.  I
      need a hip replacement, but my orthopedist wants to wait until I'm off Plavix
      before operating.  How long is long enough to be on this drug?

PMID- 23862204
TI  - New approach to fighting heart disease.  Doctors try reducing inflammation to cut
      heart-attack risk.

PMID- 23862205
TI  - Aortic aneurysm: a potential killer.  Are you at increased risk for this often
      symptomless disease?

PMID- 23862206
TI  - 12 "superfoods" you should be eating. Want to improve your health and prevent
      disease? Incorporate these nutrition-packed foods into your diet.

PMID- 23862207
TI  - Loneliness might signal mental decline ahead.

PMID- 23862208
TI  - Ask the doctor. I have chronic diarrhea because of irritable bowel syndrome
      (IBS). Should I take probiotics?

PMID- 23862209
TI  - Ask the doctor.  I have chronic sinusitis that flares up into an infection a
      couple of times each year.  Do nasal saline washes really help prevent flares?

PMID- 23862210
TI  - Hormone therapy update.  How to make sense of the new recommendations on
      postmenopausal hormone therapy.

PMID- 23862211
TI  - Repairing the heart with stem cells.  Could this experimental treatment reverse
      damage caused by a heart attack?

PMID- 23862212
TI  - Needling away chronic pain.  Research finds that acupuncture is an effective pain
      reliever.

PMID- 23862213
TI  - Preventive mastectomy.  Worry is driving some women to unnecessarily have both
      breasts removed.

PMID- 23862214
TI  - Taking more steps could reduce women's heart risks after menopause.

PMID- 23862215
TI  - Why you still need pertussis vaccination.

PMID- 23862216
TI  - Positive outlook speeds recovery.

PMID- 23862218
TI  - C- and L-band erbium-doped waveguide lasers  with wafer-scale silicon nitride
      cavities.
AB  - We report on integrated erbium-doped waveguide lasers designed for silicon
      photonic systems. The distributed Bragg reflector laser cavities consist of
      silicon nitride waveguide and grating features defined by wafer-scale immersion
      lithography and a top erbium-doped aluminum oxide layer deposited as the final
      step in the fabrication process. The resulting inverted ridge waveguide yields
      high optical intensity overlap with the active medium for both the 0.98 MUm pump
      (89%) and 1.5 MUm laser (87%) wavelengths with a pump-laser intensity overlap of
      >93%. We obtain output powers of up to 5 mW and show lasing at widely spaced
      wavelengths within both the C and L bands of the erbium gain spectrum (1536,
      1561, and 1596 nm).

PMID- 23862219
TI  - Imaginal discs can be recovered from cultured embryos mutant for the segment
      polarity genes engrailed, naked and patched but not from wingless.
AB  - Drosophila embryos homozygous for strong mutations in each of the segment
      polarity genes wingless (wg), engrailed (en), naked (nkd) and patched (ptc) form
      a larval cuticle in which there is a deletion in every segment. The mutant
      embryos normally fail to hatch but by in vivo culture we were able to show which
      could produce adult structures. Cultured wg- embryos did not produce any adult
      structures. Cultured en- embryos produced eye-antennal derivatives and rarely
      produced partial thoracic structures. nkd- and ptc- embryos produced eye-antennal
      and thoracic derivatives. The nkd- and ptc- thoracic imaginal discs developed
      with an abnormal morphology and abnormal pattern of en-expression. Our findings
      are consistent with the idea that the thoracic imaginal discs derive from two
      adjacent groups of cells that express wg and en respectively in the embryo.

PMID- 23862220
TI  - [Not Available].

PMID- 23862221
TI  - Response to Dr. Keller and her colleagues.

PMID- 23862222
TI  - Mystery solved: contact dermatitis and medical implants.

PMID- 23862223
TI  - [Establishment of an in vitro screening model for steroid 5 alpha-reductase
      inhibitors with the microplate reader].
AB  - OBJECTIVE: To establish an in vitro screening model for steroid 5 alpha-reductase
      inhibitors using the microplate reader. METHODS: Steroid 5 alpha-reductase was
      obtained from the liver of female rats, an in vitro screening model for steroid 5
      alpha-reductase inhibitors established using the 96-well plate and microplate
      reader after determination of the enzymatic activity, and the reliability of the
      model verified with the known 5 alpha-reductase inhibitors epristeride and
      finasteride. Added to the 96-well plate were the final concentrations of
      testosterone (0-40 micromol/L), NADPH (22 micromol/L), epristeride (0-60 nmol/L)
      or finasteride (0-60 nmol/ L) and steroid 5 alpha-reductase (20 microl), the
      total volume of each well adjusted to 200 microl with Tris-Hcl buffer. The 96
      well plate was placed in the microplate reader, mixed and incubated at 37 degrees
      C, followed by detection of the A340nm value at 0 and 10 min and analysis of the
      data. RESULTS: The Km value of steroid 5 alpha-reductase was 3.794 micromol/L,
      with a Vmax of 0.271 micromol/(L. min). The Ki of epristeride was 148.2 nmol/L,
      with an IC50 of 31.5 nmol/L, and the enzymatic reaction kinetic curve suggested
      that epristeride was an uncompetitive enzyme inhibitor. The Ki of finasteride was
      158. 8 nmol/L, with an IC50 of 13.6 nmol/L. The enzymatic reaction kinetic curve
      showed that both epristeride and finasteride were competitive enzyme inhibitors,
      similar to those reported in the published literature. CONCLUSION: A screening
      model was successfully established, which could rapidly and effectively screen
      steroid 5 alpha-reductase inhibitors in vitro.

PMID- 23862224
TI  - [Impact of NF-kappaB inhibitor on STAT3 translocation in PC-3 prostate cancer
      cell line].
AB  - OBJECTIVE: To observe the changes in the expressions of STAT3 and NF-KB in PC-3
      cells after IL-6 stimulation and to verify the effects of the NF-KB inhibitor
      caffeic acid phenethyl ester (CAPE) on the expressions of p-STAT3 and IL-6 in the
      PC-3 prostate cancer cell line. METHODS: PC-3 prostate cancer cells were treated
      with IL-6 at 20 ng/ml for 5, 10, 20, 30 and 45 min. The protein and mRNA
      expressions of STAT3 and NF-kappaB were measured by Western blot and real time
      PCR, respectively, and the cell cycle was detected by flow cytometry. The PC-3
      cells were exposed to TNF-alpha or TNF-alpha + CAPE, followed by determination of
      the IL-6 expression in the supernatant of the cells by ELISA and the expression
      of p-STAT3 by Western blot. RESULTS: After IL-6 stimulation, both the expression
      of p-STAT3 protein and the proliferation index of the PC-3 cells were
      significantly increased, and so were the expressions of IL-6 and p-STAT3 protein
      in the supernatant after TNF-alpha treatment (P < 0.05). TNF-alpha + CAPE induced
      statistically lower expressions of IL-6 and p-STAT3 than TNF-alpha alone (P <
      0.05). CONCLUSION: CAPE can inhibit IL-6 secretion induced by TNF-alpha in PC-3
      cells and thus suppress STAT3 translocation. Therefore, by inhibiting the
      expression of NF-kappaB and affecting STAT3 and other related cell signaling
      pathways, CAPE may become a new therapeutic option for prostate cancer.

PMID- 23862225
TI  - [Tea polyphenols inhibits the proliferation of prostate cancer DU145 cells].
AB  - OBJECTIVE: To investigate the effect of tea polyphenols on the proliferation of
      human prostate cancer cells and its possible mechanism. METHODS: We cultured
      androgen-independent prostate cancer DU145 cells in the medium with different
      concentrations (50, 100, 250 and 500 microg/ml) of tea polyphenols, and those in
      the normal medium as the control. After 48 hours of culture, we detected the
      survival rate of the cells by MTT assay and determined the expression of survivin
      by Western blot and quantitative RT-PCR. RESULTS: At 48 hours, the survival rates
      of the prostate cancer DU145 cells were 0.97 +/- 0.12, 0.71 +/- 0.07, 0.20 +/-
      0.03 and 0.08 +/- 0.01 in the 50, 100, 250 and 500 microg/ml tea polyphenols
      treatment groups, all significantly reduced as compared with the control group (P
      < 0.01) except that of the 50 microg/ml group (P = 0.42). Furthermore, the
      survival rate continued to decrease with the prolonging of time, dropping below
      5% at 96 hours except in the 50 microg/ml group. The grey values of the survivin
      expression in the 100, 250 and 500 microg/ml tea polyphenols groups were 13 425
      +/- 34, 2 017 +/- 24 and 1 274 +/- 22, respectively, at 48 hours, significantly
      lower than 15 075 +/- 48 in the control group (P < 0.01). Moreover, the content
      of survivin mRNA at 48 hours was markedly lower in the 50, 100, 250 and 500
      microg/ml treatment groups (0.74 +/- 0.03, 0.64 +/- 0.02, 0.52 +/- 0.01 and 0.21
      +/- 0.02) than in the control (P < 0.01). CONCLUSION: Tea polyphenols can inhibit
      the proliferation of human prostate cancer DU145 cells, which may be associated
      with the decreased expression of the survivin gene.

PMID- 23862226
TI  - [Inhibitory effect of Akt inhibitor deguelin on the growth of PC-3 prostate
      cancer cells].
AB  - OBJECTIVE: To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human
      prostate cancer cell lines and its possible mechanism. METHODS: PC-3 human
      prostate cancer cells were cultured in deguelin at the concentrations of 10, 100,
      500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory
      effect of deguelin on the proliferation of the PC-3 cells was determined by MTT
      assay and that on the cell cycle was detected by flow cytometry. The expression
      levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and
      GSK3beta proteins by Western blot. RESULTS: At 24, 48 and 72 hours, the
      inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer
      cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L,
      (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46
      +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/-
      2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with
      statistically significant differences from the control group (P < 0.01). Deguelin
      at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1
      phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P <
      0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/-
      5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed
      markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of
      MDM2 mRNA and proteins in the PC-3 cells treated with deguelin. CONCLUSION: Akt
      inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer
      cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt
      pathway.

PMID- 23862227
TI  - [Inhibitory effect of cocoomyxa gloeobotrydifomis on benign prostate hyperplasia
      in aged rats and its action mechanism].
AB  - OBJECTIVE: To investigate the inhibitory effect of cocoomyxa gloeobotrydifomis
      (CGD) on benign prostate hyperplasia (BPH) in aged rats and its underlying
      mechanism. METHODS: Thirty SD male rats aged 21 months were equally randomized to
      three groups, aged control, low-dose CGD and high-dose CGD, the latter two groups
      fed on a diet with CGD at 50 and 100 mg per kg per d for 3 months, while the aged
      controls on normal laboratory chow. Another 10 3-month-old male rats were
      included in a young control group and fed on the same diet as the aged control
      rats. At the end of 3 months of CGD treatment, the prostates of all the rats were
      harvested and weighed. The histomorphological and interstitial changes of the
      prostatic tissue were observed by HE staining and Masson staining, respectively.
      The expressions of phosphorylated phosphoinositide-dependent kinase 1 (PDK1),
      phosphorylated Akt (Ser 473) and phosphorylated PTEN in the rat prostate were
      determined by Western blotting. RESULTS: The wet weight and index of the prostate
      were significantly higher in the aged controls than in the young controls ([1 220
      +/- 140] vs [550 +/- 60] mg, P < 0.01; 2.08 +/- 0.17 vs 1.94 +/- 0.10, P < 0.05).
      High-dose CGD significantly inhibited the increase in the prostatic wet weight
      and index of the aged rats ([1 080 +/- 97] mg and 1.85 +/- 0.16) as compared with
      the aged controls (P < 0.01 and P < 0.05). The epithelium and interstitium,
      particularly the latter, were evidently thicker in the aged control than in the
      CGD-treated rats. The protein levels of phosphorylated PDK1 and Akt were
      significantly enhanced, while that of phosphorylated PTEN remarkably down
      regulated in the aged rats as compared with the young ones. The expressions of
      phosphorylated PDK1 and Akt were significantly decreased, whereas that of
      phosphorylated PTEN markedly increased in both the low-dose and high-dose CGD
      groups. CONCLUSION: CGD can significantly inhibit BPH in aged rats through down
      regulating the PI3K/Akt pathway.

PMID- 23862228
TI  - [Correlation of DNA methylation status of imprinted gene H19 ICR with
      oligozoospermia and asthenozoospermia].
AB  - OBJECTIVE: To study the correlation of the DNA methylation status of the
      imprinted gene H19 imprinting control region (ICR) with oligozoospermia and
      asthenozoospermia. METHODS: We eliminated chromosomal abnormality as the cause of
      male infertility in the subjects by karyotype analysis and detection of Y
      chromosome microdeletions, and identified 18 cases of single factor-induced
      oligozoospermia (sperm concentration < 15 x 10(6)/ml) and 20 cases of single
      factor-induced asthenozoospermia (progressively motile sperm <32%) by computer
      aided sperm analysis (CASA). Then we extracted genome-wide sperm DNA, treated it
      with bisul- fite, subjected the target gene fragments to PCR amplification and
      sequencing. Lastly, we analyzed the DNA methylation status of the target genes
      with BIQ Analyzer and processed the data using SPSS17.0. RESULTS: The DNA
      methylation level of the H19 ICR was increased significantly in the
      oligozoospermia patients ([9.19 +/- 2.45]%, P < 0.05), especially in the severe
      oligozoospermia males with sperm concentration < 3 x 10(6)/ml (P < 0.01), as
      compared with that of the 20 fertile control men ([0.30 +/- 0.06]%). However, no
      significant differences were found in the level ([0.30 +/- 0.07]%) and pattern of
      the DNA methylation of the H19 ICR (P = 0.62). Further analysis of the DNA
      methylation status of the CTCF-6 binding sites indicated that the DNA methylation
      degree was significant higher in the oligozoospermia men ([2.67 +/- 0.75]%) than
      in the fertile control ([0.05 +/- 0.03]%) or the asthenozoospermia group ([0.03
      +/- 0.02]%), with no significant differences between the latter two (P = 0.35).
      CONCLUSION: The reduced DNA methylation of the H19 ICR is negatively correlated
      with sperm concentration but not associated with sperm motility.

PMID- 23862229
TI  - [Male sexual dysfunction and Parkinson's disease: a preliminary investigation].
AB  - OBJECTIVE: To investigate the prevalence of male sexual dysfunction in males with
      Parkinson's disease and the pathogenesis and related factors of the problem.
      METHODS: We evaluated the sexual function of 140 men with Parkinson's disease
      using Mini-mental State Examination (MMSE), Unified Parkinson's Disease Rating
      Scale (Part III) (UPDRS III), Hoenhn-Yahr Staging (HYS), Hamilton Depression
      Scale (HAMD) and Sexual Dysfunction Standard of ICD-10. We calculated the
      Levodopa equivalent doses (LED) for all the patients. RESULTS: Sexual dysfunction
      was found in 58 (41.43%) of the patients with Parkinson's disease. There were no
      significant differences in age, education, age of onset, course of disease and
      scores on UPDRS III, HYS and LED between the sexual dysfunction and normal sexual
      function groups. The HAMD score was 14.95 +/- 9.12 in the sexual dysfunction
      group, significantly higher than 10.96 +/- 9.82 in the normal sexual function
      group (P < 0.05), and it was positively correlated with the inci- dence of male
      sexual dysfunction (P < 0.05). CONCLUSION: Sexual dysfunction is a common symptom
      in males with Parkinson's disease, and is correlated with the high HAMD score of
      Parkinson's disease patients.

PMID- 23862230
TI  - [Late-onset hypogonadism among old and middle-aged males in a rural community of
      Zhejiang Province].
AB  - OBJECTIVE: To investigate the epidemiology of late-onset hypogonadism (LOH) in
      old and middle-aged males in the rural area of Southern China. METHODS: Using the
      age-stratified sampling method, we conducted a questionnaire investigation on
      androgen deficiency in aging males (ADAM), aging male symptoms (AMS) and IIEF-5
      among 996 males aged 40 -80 years in a rural community of Jiashan county,
      Zhejiang Province from April to October 2012. We also determined the
      concentrations of serum total testosterone (TT), serum sex hormone binding
      globulin (SHBG) and serum albumin (ALB), detected the levels of free testosterone
      (cFT) and bio-available testosterone (Bio-T) by Vermeulen formula, and measured
      the volumes of the prostate and testis by ultrasonography. RESULTS: The mean age
      of the males was 56.22 +/- 8.82 years. The positive rates of LOH were 62.86% and
      23.05% based on ADAM and AMS, respectively, and the incidence of erectile
      dysfunction (ED) was 68.83%. There were significant differences among different
      age groups in the levels of luteinizing hormone (LH), SHBG, cFT and Bio-T, but
      not in TT concentration. CONCLUSION: Ours was the first survey on the
      epidemiology of LOH among old and middle-aged males in the rural area of China.
      The incidence of LOH in the rural community of Zhejiang Province was lower than
      that in the urban areas reported in other studies, but the positive rate of ED
      showed no significant difference.

PMID- 23862231
TI  - [Correlation of IPSS with IL-8 and COX-2 levels in patients with benign prostatic
      hyperplasia and prostatitis].
AB  - OBJECTIVE: To investigate the correlation of International Prostate Symptom Score
      (IPSS) with the levels of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in
      the prostate tissue and expressed prostatic secretion (EPS) in patients with
      benign prostatic hyperplasia (BPH) complicated by prostatitis. METHODS: We
      divided 80 BPH patients to be treated by transurethral resection of the prostate
      (TURP) into a simple BPH group (n = 30) and a BPH with prostatitis group (n = 50)
      based on the pathologic features. We statistically analyzed IPSS and the levels
      of IL-8 and COX-2 in EPS before surgery and the IL-8 and COX-2 levels in the
      prostate tissue after surgery. RESULTS: IPSS was positively correlated with the
      IL-8 and COX-2 levels in the prostate tissue and EPS of the BPH patients,
      moderately in the simple hyperplasia group (r > 0.5) and highly in the other (r >
      0.8). The levels of IL-8 and COX-2 in the prostate tissue and EPS were
      significantly higher in the BPH with prostatitis group than in the simple BPH
      group (P < 0.05). CONCLUSION: The levels of IL-8 and COX-2 in EPS indirectly
      reflect those in the prostate tissue. IPSS and the levels of IL-8 and COX-2 in
      EPS can help determine whether BPH is complicated by histological prostatic
      inflammation.

PMID- 23862232
TI  - [Transurethral seminal vesiculoscopy for refractory or recurrent hemospermia:
      clinical analysis of 162 cases].
AB  - OBJECTIVE: To investigate the feasibility and effect of transurethral seminal
      vesiculoscopy in the diagnosis and treatment of refractory or recurrent
      hemospermia. METHODS: We retrospectively analyzed 162 cases of refractory or
      recurrent hemospermia examined and treated by transurethral seminal
      vesiculoscopy. The patients ranged in age from 19 to 76 years and had a
      hemospermia history of 3 months to 11 years, admitted due to poor therapeutic
      results or recurrence after 4 weeks of antibiotic medication. All the patients
      underwent serum PSA examination, transrectal ultrasonography, seminal vesicle
      ultrasonography and pelvis CT or MRI before surgery. RESULTS: Wine- or magenta
      colored colloid and inflammation were found in one or both sides of the seminal
      vesicle in all the cases. Pathological biopsy revealed chronic inflammatory
      mucosa of the seminal vesicle in all the patients, and even calculi in the
      ejaculatory duct or seminal vesicle in 15 cases. Postoperative follow-up averaged
      21.7 (12 -29) months. Hemospermia disappeared or was alleviated in 150 (92.64%)
      of the cases after 1-15 ejaculations, in which 7 experienced recurrence 3 months
      later. Four cases failed to respond, and 1 developed acute bilateral epididymitis
      after surgery. No such complications as retrograde ejaculation, urinary
      incontinence or rectal injury were observed postoperatively. CONCLUSION:
      Transurethral seminal vesiculoscopy is a safe, effective and feasible new method
      for the treatment of refractory or recrudescent hemospermia.

PMID- 23862233
TI  - [Testicular cellular fibroma: a clinicopathological observation].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics, differential
      diagnosis and prognosis of testicular cellular fibroma. METHODS: We
      comprehensively analyzed the clinical presentation, histomorphology and
      immunohistochemistry of a case of testicular cellular fibroma, reviewed the
      relevant literature, and discussed its pathological features and differential
      diagnosis. RESULTS: A 30-year-old man presented with complaint of discomfort and
      painless enlargement in the right testis. The tumor was found to be a testicular
      fibroma characterized by a solid, thickly or thinly encapsulated, circumscribed
      and gray-white mass. Microscopically, fusiform cells were arranged into a
      storiform and herringbone pattern or fascicles. The tumor exhibited a great deal
      of cellularity and no nuclear polymorphisms, with a mitotic rate of 0-1/10 HP.
      Immunohistochemistry showed that the tumor cells were positive for Vimentin,
      patchily positive for S-100 and SMA, but negative for Desmin, alpha-inhibin, CD34
      and CD99. The positive rate of Ki-67 was less than 1%. CONCLUSION: Testicular
      cellular fibroma is a rare testicular sex cord stromal tumor, pathologically
      resembling its ovarian counterpart. It can be distinguished from other testicular
      spindle cell tumors by morphology and immunohistochemical staining. For the
      treatment of testicular cellular fibroma, surgical resection often has a good
      prognosis.

PMID- 23862234
TI  - [Low-dose tadalafil for erectile dysfunction following pelvic fracture-induced
      urethral injury: clinical observation of 42 cases].
AB  - OBJECTIVE: To evaluate the efficacy of daily low-dose tadalafil in the treatment
      of erectile dysfunction (ED) following pelvic fracture-induced urethral injury
      (PFUI). METHODS: Based on the length of time between pelvic fracture and the
      patients' clinic visit, we divided 42 PFUI-caused ED patients into groups A (< 1
      month), B (6-24 months) and C (> 24 months). We treated them with tadalafil at 5
      mg daily for 12 weeks consecutively, followed by evaluation of the therapeutic
      effect using IIEF-5 questionnaire and Sexual Encounter Profile (SEP) diaries.
      RESULTS: Thirty-four patients (83.3%) completed the investigation and all
      responded well to tadalafil medication. Group A showed significant differences
      from B and C in the increase of IIEF-5 scores and the positive rate of SEP.
      CONCLUSION: Daily low-dose tadalafil helps penile rehabilitation in ED patients
      following PFUI, and the earlier the medication is initiated, the better the
      effect will be.

PMID- 23862235
TI  - [Clinical efficacy of daily low-dose tadalafil on erectile dysfunction-no sexual
      life].
AB  - OBJECTIVE: Erectile dysfunction-no sexual life (ED-NS) is defined as the
      inability to have enough penile erection hardness and duration so as to have
      enough confidence in attempting sexual intercourse for more than six months. This
      study was to investigate the effect of daily low-dose tadalafil on ED-NS.
      METHODS: We treated 35 ED-NS patients aged 17-35 (25.9 +/- 3.9) years with oral
      tadalafil at 5 mg qd for 3 months and followed them up for another 3 months after
      drug withdrawal. We obtained the scores of the patients on Self-estimation Index
      of Erectile Function-No Sexual Life (SIEF-NS) and compared them before and after
      medication and at 3 months after drug withdrawal. RESULTS: The patients' SIEF-NS
      scores were 43.2 +/- 7.1 after medication and 42.1 +/- 7.4 at 3 months after drug
      withdrawal, both significantly higher than 21.2 +/- 5.9 before treatment (P <
      0.05), though there was no significant difference between the former two scores
      (P > 0.05). CONCLUSION: Daily medication of low-dose tadalafil can significantly
      improve the erectile function of the patients with ED-NS.

PMID- 23862236
TI  - [Clinical efficacy and relative factors of dendritic cell-based tumor vaccination
      for prostate cancer: a systematic review and meta-analysis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of dendritic cell (DC)-based
      vaccines in the treatment of prostate cancer, and investigate the factors that
      influence the clinical benefit rate (CBR) of the vaccines. METHODS: Based on pre
      determined search criteria, we searched the Medline database for randomized
      controlled trials on DC-based vaccines immunotherapy of prostate cancer. We
      systematically analyzed the identified studies using RevMan 5.0 and SPSS 17.0
      softwares. RESULTS: Ten randomized controlled trials involving 179 prostate
      cancer patients were identified and subjected to meta-analysis. The CBR of the DC
      vaccines for prostate cancer was 54.2% , and the objective response rate was
      7.7%. Most adverse effects were local reactions at the injection site, fever and
      flu-like symptoms. The prostate cancer patients achieved cellular immune response
      (OR = 31.12, 95% CI = 5.52-175.6, P < 0.01) and reduction of log PSA slope (OR =
      4.38, 95% CI = 1.17-16.35, P = 0.03) after administration of DC vaccines, which
      was positively correlated with CBR. The dose of DC vaccines had a significant
      correlation with CBR (OR = 5.98, 95% CI = 1.45-24.62, P = 0.01), but not the age
      of the patients (P = 0.53). Besides, density-enriched DCs achieved a higher CBR,
      while the route of administration had no effect on CBR. CONCLUSION: DC-based
      vaccines are effective, safe and well-tolerated in the treatment of prostate
      cancer. DC-mediated cellular immune response has a significant effect on CBR and
      can be used as an important index for the assessment of vaccines. More multi
      centered randomized controlled trials of higher quality and larger sample size
      are needed to provide more valid evidence.

PMID- 23862237
TI  - [Therapeutic efficacy of compound Xuanju capsule on type III prostatitis].
AB  - OBJECTIVE: To evaluate the therapeutic effect of Compound Xuanju Capsule on type
      III prostatitis. METHODS: A total of 242 patients with type III prostatitis
      diagnosed by the NIH criteria were randomly divided into an experimental and a
      control group of equal number, the former treated with Compound Xuanju Capsule +
      Tamsulosin Hydrochloride, and the latter with Quinolinone antibiotics +
      Tamsulosin and Hydrochloride, both for 6 months. After treatment, we assessed the
      therapeutic effects based on the NIH-CPSI scores and the improvement of relevant
      complications. RESULTS: All the 242 patients completed the treatment. The total
      effectiveness rate was 77.69% (94/121) in the experimental group, 71.56% (78/109)
      in those with complications. In comparison, it was only 47.10% (57/121) in the
      control group, 31.78% (34/107) in those with complications. Both the NIH-CPSI
      scores and the improvement of complications were significantly higher in the
      experimental than in the control group (P < 0.05). CONCLUSION: Compound Xuanju
      Capsule has a good therapeutic effect on type III prostatitis.

PMID- 23862238
TI  - [Molecular mechanisms of leupaxin involved in prostate carcinoma metastasis].
AB  - Leupaxin (LPXN) is a new member of the Paxillin superfamily, mainly located in
      focal adhesion plaques, involved in the transduction of multiple signaling
      pathways, and regulating the proliferation, adhesion and migration of tumor
      cells. In prostate cancer cells, LPXN is not only involved in the integrin
      signaling transduction pathway, regulating the proliferation, adhesion and
      migration of prostate cancer cells, but is also a new androgen receptor (AR)
      coactivator, regulating the transcription of nuclear AR effect genes,
      participating in AR signal transduction, and regulating the differentiation and
      invasion of prostate cancer cells. This review focuses on the molecular
      structure, special roles and molecular mechanisms of LPXN involved in prostatic
      carcinoma metastasis.

PMID- 23862239
TI  - [PSA-based screening for prostate cancer: a comparative analysis].
AB  - PSA-based screening has always been one of the controversial topics among
      urological researchers. In spite of its benefit in detecting early prostate
      cancer, PSA-based screening may not only result in widespread overdiagnosis and
      overtreatment of an often indolent disease, which is life-threatening in only a
      minority of patients, but also subject participators to such complications as
      erectile dysfunction and incontinence. Besides, whether PSA-based screening can
      reduce prostate cancer specific mortality has received considerable attention.
      This review offers a comparative analysis of recent studies on PSA-based
      screening for prostate cancer.

PMID- 23862240
TI  - [Benign prostatic hyperplasia and erectile dysfunction: an update].
AB  - Epidemiological studies have confirmed that benign prostatic hyperplasia (BPH)
      and erectile dysfunction (ED) are correlated, independent of age or comorbidities
      as diabetes. Although researchers have not yet established a direct causal
      relationship between the two problems, several pathophysiological factors may
      serve to explain it, which include the alteration in nitric oxide
      bioavailability, increased autonomic activity, a1-adrenergic receptor
      hyperactivity, imbalance of RhoA/Rho-kinase, and metabolic syndrome X. Men
      seeking care for BPH should always be screened for sexual function and complaints
      of ED. PDE5 inhibitors show promise as a future treatment for lower urinary tract
      symptoms secondary to BPH. Further investigation is required for future therapies
      and possible preventative strategies.

PMID- 23862241
TI  - Immunohistochemistry--a new era in diagnostic surgical pathology.

PMID- 23862242
TI  - Audit of custodial deaths in Karachi--an autopsy-based study.
AB  - OBJECTIVE: To assess the causes and manner of custodial deaths in Karachi, and to
      determine the factor of negligence on the part of the custodians behind such
      deaths. METHODS: The cross-sectional study involved the deaths in custody
      undergoing autopsy at Civil Hospital, Karachi, from January 2005 to December
      2010. Autopsy was followed by histological examination, X-ray or CT scan wherever
      required. A proforma was also filled as per the standard autopsy protocol.
      RESULTS: There were 61 custodial deaths in Karachi during the six-year study
      period which met the inclusion criterion. There were 58 (95.1%) males and 3
      (9.4%) females. Natural causes accounted for a majority of deaths (n = 36; 59%),
      the most common disease being coronary artery disease (n = 13; 21.3%). Unnatural
      causes accounted for 25 (41%) deaths, comprising 13 (21.3%) homicidal, 7 (11.5%)
      suicidal and 5 (8.2%) accidental. Deaths were more frequent in the age group
      ranging from 30-39 years (34.4%), while the overall age-range was from 19 to 75
      years. DISCUSSION: Measures need to be taken to provide a wholesome environment
      for the prisoners. Code of conduct for the prisoners should be followed and
      judicial procedures shall be conducted at a quick pace. Torture should be avoided
      under all circumstances, and proper vigilance shall be kept to prompt suicidal
      deaths.

PMID- 23862243
TI  - Association of economic status with breastfeeding rates in Northern Iran.
AB  - OBJECTIVE: To assess the breast-feeding condition based on economic status among
      primary school children and comparison between Turkman and non-Turkman ethnic
      groups in northern Iran in 2010. METHODS: This was a descriptive, cross-sectional
      and retrospective research study, carried out on 6882 primary school children
      (4157 = non-Turkman and 2725 = Turkman) from 112 school of urban and villages in
      the north of Iran. The schools and students were chosen by multistage sampling
      (cluster and random sampling). Breastfeeding was categorized based on World
      Health Organization classification. RESULTS: Breast-feeding during the first 6
      postpartum months and two postpartum years was found in 5.8 and 57.1% of
      children. Breast-feeding during the two postpartum years was significantly 12.5%
      more in Turkman ethnic group than non-Turkman ethnic group (P = 0.001) but breast
      feeding only for the first 6 postpartum months was 1.9% in Turkman ethnic group
      less than in non-Turkman ethnic group (P = 0.002). There was a negative
      significant association between economic status and breast-feeding during the two
      postpartum years in both ethnic groups (P = 0.001) and there was more breast
      feeding in the first 6 postpartum months in Turkman ethnic group. CONCLUSION:
      Breast-feeding rate in Turkman ethnic group is more common than non-Turkman
      ethnic group. There is an inverse relationship between economic status and breast
      feeding duration with a considerable trend in Turkman ethnic group.

PMID- 23862244
TI  - Clinical features of hepatitis B virus genotypes in Turkish patients.
AB  - OBJECTIVE: To investigate the relationship between hepatitis B virus (HBV)
      genotypes and hepatitis B early antigen (HBeAg) as well as the hepatitis C
      antibody, alanine aminotransferase (ALT) levels and liver inflammation and damage
      in chronic patients of hepatitis B. METHODS: The study was conducted at the
      Department of Microbiology, Istanbul University, Istanbul, Turkey, between June
      2002 and February 2003. Randomly selected 63 patients of chronic hepatitis B
      represented the study population. Biochemical and virological activities, and
      histopathological stages were determined in all the patients. All serum samples
      were investigated for the presence of hepatitis B virus DNA by nested polymerase
      chain reaction (PCR). The product of the reaction was sequenced by using Long
      Read Tower automated DNA sequencer. Clinical characteristics and laboratory
      features of the patients were compared using Mann-Whitney Rank Sum test, Kruskal
      Wallis test and Chi Square test for statistical analysis. RESULTS: Genotype D was
      the only type found in all patients. Of the 63 patients studied, 16 (25.4%)
      tested positive for HBeAg. Hepatitis B antigen-negative patients were more
      elderly than those who were positive (p < 0.05). The degree of hepatic
      inflammation, fibrosis stage and alanine aminotransferase levels were similar in
      both the groups (p > 0.05). Liver cirrhosis was present in 2 (4%) of the patients
      in the negative group. In terms of gender, the serum alanine aminotransferase
      levels were significantly higher in male patients than in females (p < 0.05).
      CONCLUSION: There was no relationship between the genotype of the patients and
      their response to the therapy since there was only one genotype detected in the
      study. The results showed that the hepatitis e antibody-negativity was not
      associated with good prognosis, while less necrotic activity, and alanine
      aminotransferase levels were not correlated with the severity of the disease.

PMID- 23862245
TI  - Do outcomes justify emergence of new cardiac centres.
AB  - OBJECTIVE: To assess if quality cardiac surgical results can be delivered in a
      third world country like Pakistan. METHODS: Our report focused on the initial 2
      years experience (June 2005-June 2007) at a new institution Tabba Heart
      Institute, Karachi. Individual mortality rates of adult cardiovascular surgeries
      done at our institution were compared with the Society for Thoracic Surgery
      (STS), European Association of Cardiothoracic Surgery (EACTS) databases and one
      of the more commonly applied models for predicting post-operative mortality,
      EuroSCORE. All sets of data were not adjusted for risk. RESULTS: Total of 1017
      open heart surgeries were performed. Age range for our series was 15-80 years,
      777 were men and 240 females. Of these 891 were isolated CABG, 25AVR, 50 MVR, 27
      AVR+MVR, 11 CABG+AVR and 13 CABG+MVR. 12.9% patients had LVEF < 30% and 11.7% had
      critical left main coronary disease. In all, 15% of our cases were performed on
      an emergency basis. Observed mortality rates at Tabba Heart Institute (3.94%)
      were much lower when compared to those documented by STS database (5.45%), EACTS
      (6.18%) and EuroSCORE (8.7%). CONCLUSION: With post-operative mortality an
      inverse indicator of quality health care, the results were good, despite several
      geographical, financial and demographical limitations in reproducing results
      comparable to international standards. This shows a maximum contribution in
      providing first grade cardiac support in a developing country like Pakistan.

PMID- 23862246
TI  - Line probe assay for detection of rifampicin and isoniazid resistant tuberculosis
      in Pakistan.
AB  - OBJECTIVE: To assess the efficacy of a line-probe assay delta (LiPA) as rapid
      diagnostic test for early detection of drug-resistant tuberculosis compared to
      conventional susceptibility methods in Pakistan. METHODS: Resistance to
      rifampicin (RIF) and isoniazid (INH) in 108 smear-positive pulmonary tuberculosis
      samples was detected using a line-probe assay [GenoType MTBDRplus (Hain
      Lifescience, GmbH, Nehren, Germany)] at the clinical microbiology laboratory of
      Aga Khan University Hospital in May, 2009. Results were compared with
      susceptibilities performed while using agar proportion. RESULTS: In comparison to
      the agar proportion method, the detection rate and specificity of resistance
      using MTBDR plus was 92.5% and 98.2% for rifampicin, and 76.3% and 100% for
      isoniazid. Mutations in codons 531 and 533 of rpoB gene (62%S531L) were
      responsible for 67.9% of rifampicin resistance. S315T mutation of katG gene was
      detected in 55.9% and inhA promoter mutation at positions -15 (C15T) in 11.9% of
      isoniazid resistant isolates. Four phenotypically rifampicin-resistant and 14
      isoniazid-resistant strains were not detected by MTBDRplus. Sequencing these
      strains revealed mutations in 4 strains; 2 in rpoB gene S531W, del518 and 2 in
      katG genesW300L, S315N. Hence, two phenotypic rifampicin-resistant and 13
      phenotypic isoniazid-resistant strains were not detected by the commercial line
      probe assay. CONCLUSION: The study showed that MTBDRplus had a high detection
      rate for rifampicin resistance. However, additional probes need to be included in
      the assay to improve the detection of isoniazid-resistant mycobacterium
      tuberculosis strains in Pakistan.

PMID- 23862247
TI  - Influence of smoking on lung functions in young adults.
AB  - OBJECTIVES: To determine the effect of smoking on forced vital capacity, forced
      expiratory volume in 1 sec. and the ratio between the two. METHODS: The cross
      sectional study was conducted in two Karachi-based medical colleges, Dow
      International Medical College and Bahria University Medical and Dental College
      between March 2010 and February 2011. The study comprised 244 male students (aged
      19-25 years) who were selected by simple random sampling. A detailed
      questionnaire was got filled up by each participant to assess the smoking status
      and respiratory disease symptoms. Spirometry was performed by power lab
      spirometer according to the recommended guidelines of the American Thoracic
      Society and the European Respiratory Society by highly trained power lab
      instructor. Data was analysed using SPSS version 16. Means and standard
      deviations were worked out for continuous variables, while analyses of variance
      was done to see the difference among various categories. RESULTS: A statistically
      significant difference was found in the mean spirometric values of forced
      expiratory volume, forced expiratory capacity and their ratio between the smokers
      and the non-smokers. The first two factors were significantly lower among those
      who smoked > 10-20 cigarettes/day. But there was no statistically significant
      difference in the mean ratio of passive smokers and former smokers. CONCLUSION:
      The deterioration of lung functions and habitual cough is directly related to the
      number of cigarettes smoked per day in young smokers.

PMID- 23862248
TI  - Difficulties of mothers living with mentally disabled children.
AB  - OBJECTIVE: To determine the difficulties of mothers living with children
      suffering from intellectual disabilities, and the influence of socio-demographic
      factors aggravating the situation. METHODS: The study was conducted from
      September to December 2009 in Odemis, Izmir in western Turkey, in one public
      sector and two private-sector rehabilitation centres for disabled children. The
      research sample consisted of mothers with primary responsibility for 168 disabled
      children between the ages of 3 and 18 years. Data was collected using a pre
      designed Personal Information Form, which had two sections. The first part
      contained 20 items about the socio-demographic data of the families and the
      children, their knowledge about mental disabilities and support for childcare.
      The second part consisted of 18 items which related to the most frequently
      encountered problems in terms of daily care, as well as the financial,
      psychological and social aspects. Data, collected through face-to-face interviews
      spanning 30-40 minutes, was analysed using analysis of variance and student's t
      test. RESULTS: Of the 168 mothers, 64 (38.1%) said they experienced sadness; 72
      (42.9%) anger; and 32 (19.1%) felt lonely. As many as 92 (54.8%) mothers were
      blamed by their in-laws for the disability in their respective children. Only 50
      (29.8%) parents in the study said they had "sometimes" felt acceptance of their
      disabled child. CONCLUSION: The psychological situation of parents with disabled
      children is an issue of particular concern, and psychological consultancy and
      guidance should be provided to such families to enable them to overcome their
      negative emotions and the consequent problems.

PMID- 23862249
TI  - Intracorporeal lithotripsy: a viable option for proximal ureteric stones.
AB  - OBJECTIVE: To compare the stone clearance of upper with middle and lower ureteric
      stones by using ureteroscopic pneumatic lithotripsy. METHODS: The study was
      conducted in the Department of Urology, Liaquat National Hospital, Karachi, from
      February 2009 to February 2010. A total of 90 patients were selected and divided
      into three groups of 30, each according to the location of stone in the ureter.
      All patients underwent ureteroscopic pneumatic lithotripsy with 8.5 Fr Wolf rigid
      ureteroscope and Wolf 2mm probe used for stone fragmentation. All patients were
      evaluated with X-ray KUB, ultrasound KUB and IVU. Follow-up studies included X
      ray and ultrasound KUB performed on 1st postoperative day, after 1 week and at
      the end of 2nd week. Presence of stone after last follow-up was considered as
      failure of the procedure. RESULTS: Total number of patients were 90 and mean age
      was 27.47 +/- 5.8 years. Male female ratio was 2.1:1. Mean stone size was 11.44
      +/- 1.41mm. According to the location of the stones, the success rate of
      pneumatic lithotripsy for upper, middle, and lower ureteral stones was 86.7%,
      93.3%, and 96.7% respectively. Completely fragmented stones cleared spontaneously
      within two weeks in 83 of 90 cases so the overall stone-free rate was 92.2%.
      CONCLUSION: Ureteroscopic Pneumatic Lithotripsy is an acceptable form of
      treatment for upper ureteric calculi in addition to middle and lower ureteric
      calculi. It is a simple, reliable, effective, rapid and safe procedure.

PMID- 23862250
TI  - Knowledge and practice of urban Iranian pregnant women towards folic acid intake
      for neural tube defect prevention.
AB  - OBJECTIVE: To assess the knowledge and practice of urban Iranian pregnant women
      regarding periconceptional folic acid intake for neural tube defect (NTD)
      prevention. METHODS: The population-based study was done on 676 primiparous women
      in an urban area in Golestan province in northern Iran from June to November,
      2008. A questionnaire was completed by the subjects regarding their knowledge of
      folic acid. Questionnaires were administered to women who were seeking routine
      antenatal care at health centres, private gynaecological clinic and the Dezyani
      Gynaecologic and Obstetric Hospital. Questions covered knowledge and use of folic
      acid supplements and demographic and socioeconomic characteristics. RESULTS: Out
      of the 676 women surveyed, 96.2% reported that they heard of folate. Of these,
      only 27.6% knew that folate was something important in the prevention of neural
      tube defects. Overall, 20.12% of the total women took folic acid during
      periconceptional period. The most common information sources on folate were
      healthcare service (54.5%). Besides, 37.6% of the subjects who heard about folate
      were aware that green leafy vegetables were fortified with folic acid. In
      univariate analysis, knowledge and intake of folic acid was not associated with
      education and the age of women. CONCLUSION: A healthcare plan for intervention to
      increase the knowledge and intake of folic acid by pregnant women during the
      protective period is required.

PMID- 23862251
TI  - Estimation of serum nicotine by gas chromatography in smokers, passive smokers
      and never smokers.
AB  - OBJECTIVE: To compare the serum nicotine levels in smokers, passive smokers and
      those with no exposure to cigarette smoke. METHODS: The comparative study
      spanning two years was conducted in Ziauddin Medical University, Karachi, in
      collaboration with HEJ Research Institute of Chemical Sciences, University of
      Karachi from 2009 to 2011 involved 135 self-reported smokers, never smokers and
      passive smokers among whom serum nicotine was analysed using 17-A gas
      chromatograph with flame ionisation detector equipped with Supelco SPB-5 fused
      silica capillary column (45m x 0.53mm id and 0.5 um) attached with Class GC 10
      Software. SPSS version 11.0 and Kruskal Wallis Test were used for statistical
      purposes. RESULTS: There were 43 (32%) smokers, 61 (45%) passive smokers and 31
      (23%) never smokers in the study. Among the smokers 33 (77%) had serum nicotine
      greater than 10 ng/ml. The mean nicotine concentration of smokers was 55 +/- 6.1
      ng/ml and mean rank was 98.3 which was significantly higher than passive and
      never smokers (p < 0.01). CONCLUSION: The method for the estimation of serum
      nicotine was fairly reliable. Serum nicotine was raised in smokers, and the
      effects of passive smoking was also seen through serum nicotine. However, more
      studies with increased sample size are required to establish it as an
      environmental tobacco smoke exposure marker.

PMID- 23862252
TI  - Hepatic vein waveform in liver cirrhosis: correlation with child's class and size
      of varices.
AB  - OBJECTIVE: To determine the correlation of hepatic venous waveform changes with
      severity of hepatic dysfunction and grading of oesophageal varices. METHODS: A
      cross-sectional analytical study was conducted at Jinnah Postgraduate Medical
      Centre, Karachi, Medical Unit-III, Ward-7 from January 2009 to December 2009.
      Cirrhotic patients with portal hypertension were included in study. Patients
      presented with acute variceal bleeding, previous treatment with beta blockers or
      nitrates, sclerotherapy endoscopic band ligation, portal vein thrombosis, severe
      clotting defects, hepatic encephalopathy grade III or IV and noncirrhotic portal
      hypertension; were excluded from the study. Upper G I endoscopy was carried out
      in all patients after informed consent. Oesophageal varices were classified
      according to Baveno III while hepatic function was assessed and grouped by Child
      Pugh classification. Colour Doppler ultrasound was carried out on all patients.
      Their waveforms were classified as monophasic, biphasic triphasic and the
      correlation of these hepatic vein waveforms with Child-Pugh class and size of
      oesophageal varices was evaluated. Statistical significance was defined as
      P?0.05. RESULTS: Total of 65 patients who met the inclusion criteria and included
      in the study with mean age of 47.39 +/- 10.91 (range 23-70) years. Among these 51
      (78.5%) were males while 14 (21.5%) were females. On the basis of hepatic
      function 32 (49.2%) patients presented in Child-Pugh Class A, 23 (35.4%) with
      Class B and 10 (15.4%) patients had Class C. Hepatic venous waveform was
      triphasic in 5 (7.7%), biphasic in 18 (27.7%), and monophasic in 42 (64.6%)
      cases. The relationship of these waveforms had significant relation with hepatic
      dysfunction (p < 0.012) while insignificant with grading of oesophageal varices
      (p 0.29). Upper GI endoscopy revealed large grade varices in 37 (56.9%) patients,
      17 (26.2%) patients had small grade varices while no varices were found in 11
      (16.9%) patients. CONCLUSION: Hepatic venous waveform pressure changes have
      significant relation with severity of hepatic dysfunction but insignificant
      relation with grading of oesophageal varices. Further studies using a combination
      of various Doppler parameters are required to create indices with a better
      predictive value.

PMID- 23862253
TI  - Exploring the process of final year objective structured clinical examination for
      improving the quality of assessment.
AB  - OBJECTIVE: To explore the process of final year Objective Structured Clinical
      Examination (OSCE) for improving the quality of assessment. METHODS: The
      analytical cross-sectional study was conducted with purposive sampling on one
      year Medicine Objective Structured Clinical Examination (OSCE) scores of Final
      Year batch of 2009 at the Shifa College of Medicine, Islamabad. The scores from
      December 2008 to December 2009 of 77 Final Year students were analysed. The
      process of examination and the interpretation of the scores was evaluated using
      the Standards for Educational and Psychological Testing as the conceptual
      framework for validity testing which identifies five sources of test validity
      evidence. Internal consistency reliability of the examination was determined by
      Cronbach's alpha. Comparison and Correlation between students' end-of-clerkship
      (EOC) and end-of-year (EOY) examination scores were analysed by paired sample t
      test and Pearson's Correlation Coefficient respectively. RESULTS: There was no
      significant positive correlation between the scores of end-of-clerkship and end
      of-year Medicine Objective Structured Clinical Examination. Overall, the
      students' performance in the former segment was better. Evaluation of exam
      stations showed that mean scores significantly decreased in almost all end-of
      year stations. Reliability decreased from 0.53 in the former to 0.48 in the
      latter assessment. Validity evidence showed that content validity was established
      by blueprinting of the objective exam. Response process evidence revealed that
      checklists, response key and rating scale were discussed with the faculty
      observing the stations. However, lack of other important sources of validity like
      standard setting for pass/fail criteria and poor reliability are serious threats
      to the validity of such exam scores. CONCLUSIONS: Multiple sources of validity
      evidence are needed to make defensible assumptions from performance scores.
      Consideration of all sources and threats to validity evidence is important to
      improve the quality of assessment.

PMID- 23862254
TI  - Frequency and severity of perineal tears in Countess Lady Duffrin Fund Hospital,
      Hyderabad.
AB  - OBJECTIVE: To observe the frequency and severity of perineal tears during vaginal
      delivery. METHODS: It was a prospective observational study done at the Countess
      Lady Duffrin Fund Hospital, Hyderabad, Pakistan, from December 1, 2009 to May 31,
      2010. Women with full-term singleton pregnancy primigravida or multigravida, in
      active labour were included in the study. Patients with pre-term labour, breech
      presentation and antepartum haemorrhage were excluded, leaving the study
      population to be 147/1488. A predesigned structured proforma was used after
      informed verbal consent by the patient. All results were analysed on SPSS version
      11. Frequencies and percentages were calculated, while Spearman's rho test (two
      tailed) was applied for categorical variables. A p-value of less than or equal to
      0.05 was considered significant. RESULTS: The frequency of perineal tears in our
      study was 147/1488 (9.8%). The mean age was 28.08 +/- 7.47, ranging between 17-42
      years. The vast majority, 100 (68%) delivered spontaneously, 45 (30.6%) were
      delivered with help of the forceps, and only 2 (1.4%) had vacuum delivery.
      Parity, oxytocin use, mediolateral episiotomy, forceps use, weight of babies >
      3.6 kg were significantly associated with perineal tears. CONCLUSION: Perineal
      tears cause considerable post-natal morbidity. Identification of risk factors,
      vigilant monitoring during labour and good perineal support is recommended for
      minimising the risk of perineal trauma as well as morbidity.

PMID- 23862255
TI  - Spinal anaesthesia for caesarean section: plain vs hyperbaric bupivacaine.
AB  - OBJECTIVE: To compare the clinical characteristics of sensory and motor block as
      well as haemodynamic stability using plain and hyperbaric bupivacaine in spinal
      anaesthesia for caesarean section. METHODS: Two equal groups were formed from a
      total of 60 patients who were enrolled in this prospective randomised double
      blinded study that was done at tertiary care hospital in Karach, during 2005 to
      2006. Equal volume of plain and hyperbaric bupivacaine 10 mg with 25 mcg of
      fentanyl was used for spinal anaesthesia in the two groups that were formed on
      the basis of random allocation. Characteristics of sensory and motor block,
      episodes of hypotension and bradycardia as well as use of ephedrine and atropine
      were recorded by blinded investigator. RESULTS: There was no difference in the
      onset of block, time to achieve maximum level of block and haemodynamic
      parameters between the two groups. However, plain bupivacaine took more time for
      two dermatomes sensory level regression below T4, and resulted in prolonged block
      duration. No statistically significant difference was found for episodes of
      hypotension, bradycardia and use of ephedrine and atropine. CONCLUSIONS: In
      obstetric population, both plain and hyperbaric bupivacaine 10 mg, with fentanyl
      produced adequate anaesthesia for caesarean section without any differences in
      the time of onset, extent of the block and haemodynamic parameters. However,
      sensory level regression was delayed in the plain group which may have caused
      prolonged duration of block.

PMID- 23862256
TI  - Causes of tooth extraction at a tertiary care centre in Pakistan.
AB  - OBJECTIVE: To evaluate the frequency of common causes of permanent tooth
      extraction and severity of dental condition at the time of tooth extraction.
      METHODS: The cross-sectional study was conducted at the Department of Oral and
      Maxillofacial Surgery, Punjab Dental Hospital, Lahore, Pakistan, from February to
      June 2010, and involved 1026 patients who were referred for the extraction of
      permanent teeth. The inclusion criteria comprised caries, periodontitis,
      restoration failure, trauma, and local pathologies, while 3rd Molar impactions,
      supernumerary tooth extraction and extractions done as part of orthodontic or
      prosthodontic treatment were excluded. Oral hygiene was recorded using the
      Simplified Oral Hygiene Index. SPSS version 17 was used for statistical analysis.
      RESULTS: The mean age of the study population was 46.60 +/- 11.321 years, and
      there were 611 (59.6%) males. A total of 1178 teeth were extracted. Advanced
      dental caries was the leading cause of tooth extraction (n = 743; 63.1%),
      followed by periodontitis (n = 309; 26.2%) restoration failure (n = 54; 4.6%),
      trauma (n = 38; 3.2%) and miscellaneous local pathologies (n = 34; 2.9%). More
      than half of the patients (n = 540; 52.6%) had poor oral hygiene. CONCLUSION:
      Advanced dental caries is the most common cause behind tooth extraction.

PMID- 23862257
TI  - Significance of primary factors influencing students' performance at the College
      of Dentistry, King Saud University, Saudi Arabia.
AB  - OBJECTIVE: To determine the effect of different enabling factors such as
      curriculum, role of faculty, academic advising and availability of learning
      resources and supportive services on the performance of students pursuing their
      Bachelor's degree in dentistry. METHODS: Data was collected from the male and
      female students of the College of Dentistry, King Saud University, during the
      academic year 2008-2009. All undergraduate students (576) constituted the total
      sample size of the study. The respondents were requested to fill a questionnaire
      form, which was specially designed in accordance with requirements of the
      Association for Dental Education in Europe (ADEE). The questionnaire comprised 45
      questions addressing all aspects of the relevant factors. The five-point Likert
      scale was used to evaluate the feedback. All the responses (239) were thoroughly
      examined and only the completely filled forms (169) were subjected to regression
      analyses, taking student's CGPA as a dependent factor and a depiction of their
      performance. The t-tests were also worked out to evaluate variations in the
      responses of male and female students to each sub-factor. RESULTS: The study
      showed a significant impact of faculty and learning resources and support
      services on a student's achievement (alpha = 0.05). Surprisingly, academic
      advising and the dental curriculum had non-significant effect at 95% level of
      confidence. However, the critical analyses acknowledged that the non-significant
      impact was due to poor performance of the two factors. CONCLUSION: The role of
      faculty and learning resources as well as of support services had significant
      effect on students' performance. However, there is an immense need to improve the
      level of academic advising and revise the curriculum to have a significant impact
      of these factors on the student's achievements.

PMID- 23862258
TI  - Effects of rapamycin and tacrolimus on mature endothelial cells and endothelial
      progenitor cells.
AB  - OBJECTIVE: To investigate the effects of the potent immunosuppressive agents
      tacrolimus and rapamycin on the number of circulating mature endothelial cells
      and circulating endothelial progenitor cells in an experimental model. METHODS:
      It was an experimental study performed from December 2007 to January 2008 in
      which the effects of the immunosuppressive agents tacrolimus and rapamycin on
      endothelial progenitr cells and circulating mature endothelial cells were
      analysed on 24 male wistar albino rats in a controlled environment model.
      Circulating cell populations were measured by flow-cytometric analysis. Maun
      Whitney U test and analysis of vartiance were used for statistical purposes.
      RESULTS: Rapamycin increased the number of circulating mature endothelial cells
      approximately 2-fold compared to tacrolimus. The number of endothelial progenitor
      cells also was increased in the peripheral blood of rats treated with rapamycin
      compared to those treated with tacrolimus. CONCLUSION: The study showed that
      treatment with rapamycin is associated with an increase in endothelial progenitor
      cells and circulating mature endothelial cells. This increase may be associated
      with endothelial cell damage and repair.

PMID- 23862259
TI  - Observer variation in MRI evaluation of patients with suspected lumbar disc
      herniation and nerve root compression: comparison of neuroradiologist and
      neurosurgeon's interpretations.
AB  - OBJECTIVE: To analyse inter-observer variation between a neuroradiologist and
      neurosurgeon in the MRI diagnosis of lumbar nerve root compression. Although
      lumbar MFI is primarily analyzed and reported by a radiologist, neurosurgeons
      often analyse it independently as they have sufficient clinical background as
      well as radiological expertise to diagnose most spinal pathologies on Magnetic
      Resonance Imaging (MRI). METHODS: Retrospective analysis was carried out for
      images of 54 patients who underwent MRI between March and July 2010 of lumbar
      spine with suspected lumbar disc herniation and nerve root compression, at Aga
      Khan Hospital, Karachi, Pakistan. One fellowship trained neuroradiologist and one
      neurosurgeon evaluated the images on PACS system separately. Both observers were
      unaware of the patient's clinical history and each other's findings. Lumbar discs
      at L3-L4, L4-L5 and L5-S1 levels were evaluated by both observers for disc
      disease and nerve compression. Findings were recorded on a proforma and analysed
      with SPPS Version 16. RESULTS: Total 162 lumbar discs were studied by both
      readers in 54 patients. Excellent inter-observer agreement was seen for the
      presence or absence of nerve root compression (Percentage agreement = 88.89%; k =
      0.774; p = 0.737). For disc bulge, inter-observer agreement was fair but
      statistically insignificant (Percentage agreement = 72.84%; k = 0.414; p =
      0.132). In case of disc herniation, although inter-observer agreement was fair,
      but the difference was statistically significant (Percentage agreement = 84.57%;
      k = 0.511; p = 0.002). CONCLUSION: Inter-observer agreement between
      neuroradiologist and neurosurgeon in diagnosing nerve root compression due to
      lumbar disc disease was excellent. Agreement regarding disc bulge and herniation
      was fair.

PMID- 23862260
TI  - A critical appraisal of the evidence regarding the choice of common bearing
      couples available for total hip arthroplasty.
AB  - There are a variety of materials used in bearing components in total hip
      replacement (THR). Metal-on-polyethylene replacements, having undergone small
      technical refinements in design over the last 30- 40 years, give, according to
      the Scandinavian hip register, very good 10-year outcomes. However, aseptic
      loosening, caused to a great extent by adverse biological local reactions,
      induced by wear products from the articular surfaces, remains a serious problem.
      Thus, the debate and challenge of finding the best bearing surfaces continues.
      Technical improvements have been advocated in recent times to improve the
      replacement bearing longevity. Other than discussing such improvement, the paper
      looks at the evidence surrounding materials that are commonly used in total hip
      arthroplasty. This has been done to empower surgeons to make more informed
      decisions when choosing the bearing surfaces for their patients.

PMID- 23862261
TI  - Women trafficking: causes, concerns, care!
AB  - Pakistan is both a country of origin and destination as far as women trafficking
      is concerned. Poverty, gender discrimination, lack of education, and ignorance
      about legal rights are some of the underlying causes. Available data suggest
      several areas of concern, like, for instance: direct health effects, maladaptive
      coping leading to the use of illicit drugs, and inaccessibility to healthcare
      facilities. Therefore, numerous interventions would be required at three levels:
      the prevention of trafficking, the protection of victims and the prosecution of
      the traffickers.

PMID- 23862262
TI  - Emergency triage: extend of our knowledge.

PMID- 23862263
TI  - Magnetic resonance imaging of metronidazole induced encephalopathy.
AB  - We describe a case demonstrating Magnetic Resonance (MR) imaging findings in
      association with Metronidazole (Flagyl) toxicity. MRI brain showed abnormal
      signal intensity involving dentate nuclei of cerebellum bilaterally symmetrical.
      The diagnosis of metronidazole toxicity was made by the MR imaging findings and
      supported clinically. In hospital, course of treatment drug was discontinued.
      Patient improved clinically with discontinuation of metronidazole. No follow-up
      MR imaging was obtained. In this report, we present a case depicting MR imaging
      changes within the dentate nuclei of cerebellum.

PMID- 23862264
TI  - Idiopathic pulmonary haemosiderosis presenting as severe iron deficiency anaemia-
      a case from Pakistan.
AB  - Idiopathic pulmonary haemosiderosis is an uncommon disorder, which is
      characterized by iron deficiency, recurrent haemoptysis and diffuse parenchymal
      infiltration on chest radiograph. We report an 8 year old child who had past
      history of multiple blood transfusions with diagnosis of iron deficiency anaemia
      and recurrent chest infection since the age of 21/2 year. At the age of 8 years,
      the child presented with fever and severe respiratory distress requiring
      intubation and ventilation. On Chest X-ray, bilateral white out was found and CT
      scan lung showed diffuse alveolar involvement. Lung biopsy confirmed haemosiderin
      laden macrophages. Child was put on steroids and despite severe anaemia (Hb 3.2
      g/dl), he showed improvement and survived. To our knowledge, this is the first
      case of idiopathic pulmonary haemosiderosis reported from Pakistan.

PMID- 23862265
TI  - Primary percutaneous coronary intervention in a patient with dextrocardia.
AB  - The case of a 40-year-old male with dextrocardia who presented with ST Elevated
      Myocardial Infarction (STEMI) is reported. Coronary angiogram was performed after
      due manipulation and then successful primary percutaneous coronary intervention
      (PCI) of Left anterior descending (LAD) coronary artery was done. His 9 months
      follow up primary PCI in a patient with angiogram revealed patent stent in
      proximal LAD. There are very few published case reports of this rare congenital
      anomaly addressing technical details of successful primary PCI with dextrocardia.

PMID- 23862267
TI  - Tracheo-esophageal fistula secondary to tracheostomy, delayed diagnosis.
AB  - Persistent air leak is not a common problem in patients who are under mechanical
      ventilation support; however, it can be encountered in intensive care unit (ICU).
      It is often due to nonuniform contact between the cuff and the tracheal wall
      caused by insufficient cuff pressure or malposition of the tube. Tracheostomy is
      commonly applied and is a relatively safe invasive procedure in ICU. We report a
      case of tracheoesophageal fistula (TEF), secondary to tracheostomy, initially
      manifested with persistent air leak under mechanical ventilation in ICU.
      Consequently, TEF should be considered in patients with unexplained upper airway
      leaks.

PMID- 23862266
TI  - Fenofibrate-induced rhabdomyolysis in a patient with stage 4 chronic renal
      failure due to diabetes mellitus.
AB  - Rhabdomyolysis is defined as a pathological condition of skeletal muscle cell
      damage leading to the release of toxic intracellular components into the
      circulation. Several factors may lead to rhabdomyolysis. Fenofibrate is a fibric
      acid derivative agent that is used in the treatment of hyperlipidaemia. Although
      several case reports of rhabdomyolysis have been reported due to the combination
      of statin and fenofibrate, fenofibrate alone rarely causes rhabdomyolysis. When
      administering fenofibrate in chronic renal failure, dose should be adjusted.
      Here, we report a case with fenofibrate-induced rhabdomyolysis in a patient with
      chronic renal failure.

PMID- 23862268
TI  - Coronary aneurysm complicated by acute myocardial infarction.
AB  - The case of a 55 years old, hypertensive, obese female is presented, who came to
      the emergency department with inferoposterior ST segment elevation myocardial
      infarction (STEMI) with right ventricular infarction. After thrombolytic therapy,
      she reperfused but had anginal symptoms on minimal activity. The patient
      underwent coronary angiogram which showed aneurysmal right coronary artery (RCA)
      with 60% stenosis and thrombus in mid portion and distal bifurcation of RCA with
      TIMI III distal blood flow. Left main coronary artery was normal. Left anterior
      descending (LAD) and Left circumflex (LCX) arteries were also aneurysmal and non
      obstructive. The patient was started on intravenous heparin and warfarin in view
      of aneurysmal coronary arteries and large thrombus burden. The patient was
      discharged home in one week and is doing well at follow up.

PMID- 23862269
TI  - Is prophylactic antibiotic treatment justified in neonates?

PMID- 23862270
TI  - Extending the window for thrombolysis in acute stroke.

PMID- 23862271
TI  - Knowing your rights in medical research and how to blow the whistle?

PMID- 23862272
TI  - Mechanical complications following acute myocardial infarction.
AB  - OBJECTIVE: To outline the outcome and management of patients with acute
      myocardial infarction presenting with mechanical complications such as post
      infarction ventricular septal defect, mitral regurgitation and left ventricular
      rupture. METHODS: The retrospective study, conducted in September and October,
      2010 at the Aga Khan University Hospital, Karachi, included cases from January
      1990 to December 2009. Only 18 cases were found who had presented with such
      complications. They were assessed for demographics as well as pre-operative, per
      operative and post-operative management patterns. Data was analysed using SPSS
      version 17.0. RESULTS: Out of the 18 patients, 10 had post-infarction ventricular
      septal defect, while 8 had mitral regurgitation defects. The mean time from
      myocardial infarction to the diagnosis of mechanical complications was 5.28 +/-
      4.07 days, and from diagnosis to repair was 2.00 +/- 1.49 days. Overall, there
      were 3 in-hospital mortalities. CONCLUSION: The optimal timing of surgical
      intervention has always remained debatable. A high-level of clinical suspicion
      and earlier intervention can reduce morbidities and mortalities.

PMID- 23862273
TI  - Attitude and practice of patients and doctors towards complementary and
      alternative medicine.
AB  - OBJECTIVES: To determine the attitude towards complementary and alternative
      medicine among the doctors and patients. METHODS: The study was carried out at
      Civil Hospital Karachi and Liaquat National University Hospital, Karachi during
      April to September 2010. Two sets of questionnaires were developed separately for
      doctors and patients. Each set consisted of queries regarding demographic data of
      patients and doctors. The questionnaire for the patients contained questions
      reflecting the general attitude, mode of complimentary and alternative medicine
      usage, disease referred and the underlined reasons behind pricking the options.
      The questionnaires for doctors in general laid focus on the personal opinion
      about the practice not only for their own use, but also related to their concern
      towards those patients who used complimentary and alternative medicine.
      Predictive analysis software statistics 18 was used for statistical analysis.
      RESULTS: Of the patients, 237 (59.3%) used complimentary and alternative
      medicine. Herbal medicine followed by homeopathic medicine were the most commonly
      used therapies. Fever and cough were the most common diseases for which patients
      used the options. The preference was mainly based on inter-personal
      communications, reliance on complimentary and alternative medicine, and financial
      restriction. Concealing from the doctors was common in patients. Only 62 (34.4%)
      out of 180 doctors used complimentary and alternative medicine themselves.
      Refusal by other doctors was because they considered the option ineffective,
      obsolete and unsatisfactory. About half of the doctors forbade the patients to
      use such therapies, but 31% (n=73) patients ignored the doctor's advice.
      CONCLUSION: The use of complimentary and alternative medicine is highly prevalent
      in our society by patients irrespective of their social class. Preference for
      such therapies, on the other hand, is quite low among medical doctors as they
      consider allopathic medicine to be effective.

PMID- 23862274
TI  - Evolution, not revolution: the answer to problems of undergraduate medical
      education in Pakistan.

PMID- 23862275
TI  - Holistic or wholistic?

PMID- 23862276
TI  - Thoughts on spiritual care.

PMID- 23862277
TI  - Energy therapies in Christian nursing? Part 1.

PMID- 23862278
TI  - Helping Sam slay the dinosaur.

PMID- 23862279
TI  - I'm not your honey.

PMID- 23862280
TI  - Spirit-guided care: Christian nursing for the whole person.
AB  - Healthcare today is challenged to provide care that goes beyond the medical model
      of meeting physical needs. Despite a strong historical foundation in spiritual
      whole person care, nurses struggle with holistic caring. We propose that for the
      Christian nurse, holistic nursing can be described as Spirit-guided care-
      removing oneself as the moiatiating force and allowing Christ, in the furm of the
      Holy Spirit, to flow through and guide the nurse in care of patients and
      families.

PMID- 23862281
TI  - Picture this! Using photovoice to facilitate cultural competence in students.
AB  - The use of digital images is a prevalent practice in today's society, especially
      in social media. Photovoice is a qualitative research methodology used to express
      the experiences of participants from a variety of populations. Photovoice can be
      utilized as a teaching and learning tool to facilitate cultural competence among
      undergraduate nursing students.

PMID- 23862282
TI  - Creating a culture for evidence-based practice in the faith community.
AB  - Faith community nurses (FCN) are in an ideal position to lead the faith community
      in creating structures and models to integrate research and evidence-based
      practices into faith-based ministries. In transforming an organization, the FCN
      considers ways to educate the community on the value of research. By embracing
      research as a method for informing practice, the FCN plays a vital role in
      evaluating faith-based interventions.

PMID- 23862283
TI  - The humbled expert: an exploration of spiritual care expertise.
AB  - This interpretive phenomenological study explored how inpatient palliative care
      nurse consultants provide spiritual care and how they acquired these skills.
      Humbled experts describes the nurses' personhood and spiritual care practices,
      offering insight for skilled spiritual care in any setting.

PMID- 23862284
TI  - Teamwork.
AB  - Teamwork is a widely used term to describe two or more people working together
      well. This article describes a special kind of teamwork in nursing--when nurses
      come together in a supportive way that enables them to be more than they could be
      alone to accomplish difficult tasks and provide the best in patient care and
      healthcare leadership.

PMID- 23862285
TI  - Do motivational gifts impact nurses' job fit and satisfaction?
AB  - Given the growing need for nurses, this study explored the presence in nurses of
      the seven motivational gifts given in the biblical passage of Romans 12:3-8, and
      relationships between the gifts and nurses' job satisfaction and person-job fit.
      Results confirm Romans 12 motivational gifts in nurses and suggest potential
      usefulness in knowing nurses'gift profiles for recruitment, job satisfaction, and
      job placement.

PMID- 23862286
TI  - A journey of learning...nothing is wasted.
AB  - A nursing student relays how a 10-year career in missions led her to her life
      purpose--to work as a maternal child nurse and improve the health of women. She
      relays three invaluable lessons she learned from being a missionary that apply to
      all nurses.

PMID- 23862287
TI  - Why is prayer important?

PMID- 23862288
TI  - Selflessness in nursing: a win-win-win situation.

PMID- 23862289
TI  - Mentoring or mimicking?

PMID- 23862290
TI  - I nearly missed Jesus.

PMID- 23862291
TI  - Sleep-related behaviors and beliefs associated with race/ethnicity in women.
AB  - Explore how social factors influence sleep, especially sleep-related beliefs and
      behaviors. Sleep complaints, sleep hygiene behaviors, and beliefs about sleep
      were studied in 65 black/African American and white/European American women.
      Differences were found for snoring and discrepancy between sleep duration and
      need. Sleep behaviors differed across groups for napping, methods for coping with
      sleep difficulties, and nonsleep behaviors in bed. Beliefs also distinguished
      groups, with differences in motivation for sleep and beliefs about sleep being
      important for health and functioning. These findings have important public health
      implications in terms of developing effective sleep education interventions that
      include consideration of cultural aspects.

PMID- 23862292
TI  - Medical mistrust influences black women's level of engagement in BRCA 1/2 genetic
      counseling and testing.
AB  - Clinical evidence supports the value of BRCA1/2 genetic counseling and testing
      for managing hereditary breast and ovarian cancer risk; however, BRCA1/2 genetic
      counseling and testing are underutilized among black women, and reasons for low
      use remain elusive. We examined the potential influence of sociocultural factors
      (medical mistrust, concerns about genetic discrimination) on genetic counseling
      and testing engagement in a sample of 100 black women at increased risk for
      carrying a BRCA1/2 mutation. Eligible participants fell into 1 of 3 groups: (1)
      healthy women with at least 1 first-degree relative affected by breast and/or
      ovarian cancer, (2) women diagnosed with breast cancer at age less than or equal
      to 50 years; and (3) women diagnosed with breast and/or ovarian cancer at age
      greater than or equal to 50 years with either 1 first-degree relative or 2 second
      degree relatives with breast and/or ovarian cancer. Participants were recruited
      from clinical anid community settings and completed a semistructured interview.
      Study variable relationships were examined using bivariate tests and multivariate
      regression analysis. As expected, genetic counseling and testing engagement among
      this sample was low (28%). After accounting for;sociodemographic factors and self
      efficacy (beta=0.37, p<.001), women with higher medical mistrust had lower
      genetic counseling and testing engagement (beta=-0.26, p<.01). Community-level
      and individual interventions are needed to improve utilization of genetic
      counseling and testing among underserved women. Along with trust building between
      patients and providers, strategies should enhance women's personal confidence.
      The impact of medical mistrust on the realization of the benefits of personalized
      medicine in minority populations should be further examined in future studies.

PMID- 23862293
TI  - Effects of social ties on self-rated physical health among African American
      adults.
AB  - OBJECTIVES: To examine associations between social ties and self-rated physical
      health among midlife and older African Americans. METHODS: Cross-sectional
      analysis of the 2005-2006 Milwaukee African American oversample of the second
      Midlife Development in the United States (MIDUS II) study. Multivariate logistic
      regression examined associations between type of social ties (family or friends),
      their frequency (number of contacts), and their quality (support and strain) with
      betterself-rated physical health (SRPH). We defined better SRPH to include self
      reports of good, very good, or excellent SRPH: this category was compared with
      fair or poor SRPH. Control variables included demographic factors; social
      engagement characteristics such as working, volunteering, and caregiving; and
      measures of social structure such as types of discrimination experience and
      ratings of neighborhood quality. RESULTS: In adjusted results, each additional
      degree of family support was associated with better self-rated physical health
      (odds ratio [OR], 1.59; 95% confidence interval (CI], 1.14-2.22). Each additional
      reported incident of daily discrimination was associated with 9% lower odds of
      reporting better SRPH (OR, 0.91; CI, 0.83-0.99). DISCUSSION: Results suggest
      quality of family support may contribute importantly to the health of African
      Americans. When working with midlife and older African Americans, providers
      should engage and support families as a vital resource to improve health.

PMID- 23862294
TI  - Cultural barriers to African American participation in anxiety disorders
      research.
AB  - Anxiety disorders are understudied, underdiagnosed, and undertreated in African
      Americans. Research focused on the phenomenology, etiology, and treatment of
      anxiety in African Americans has been hampered by lack of inclusion of this
      population in clinical research studies. The reason for exclusion is not well
      understood, although cultural mistrust has been hypothesized as a major barrier
      to research participation. This article reviews the relevant literature to date
      and examines the experience of 6 African American adults who participated in a
      larger clinical assessment study about anxiety. Drawing upon in-depth
      semistructured interviews about their subjective experiences, we examined
      participant perspectives about the assessment process, opinions about African
      American perception of anxiety studies, and participant-generated ideas about how
      to improve African American participation. Based on a qualitative analysis of
      responses, feelings of mistrust emerged as a dominant theme. Concerns fell under
      6 categories, including not wanting to speak for others, confidentiality, self
      and group presentation concerns, repercussions of disclosure, potential covert
      purposes of the study, and the desire to confide only in close others.
      Suggestions for increasing African American participation are discussed,
      including assurances of confidentiality, adequate compensation, and a comfortable
      study environment.

PMID- 23862295
TI  - Alcohol dependence and health care utilization in African Americans.
AB  - OBJECTIVE: Ethnic and cultural differences in patterns of alcohol use disorders
      must be understood in order to address improvement in prevention of such
      disorders and accessibility to health care services. The purpose of this study
      was to evaluate factors that influence the utilization of medical and mental
      health services among alcohol-dependent and non-alcohol-dependent African
      Americans. METHOD: A cohort of 454 African Americans was evaluated. Alcohol
      dependent participants were recruited from various inpatient treatment facilities
      in the Washington, DC, metropolitan area and through advertisement and word of
      mouth. Non-alcohol-dependent participants were recruited by advertisements. Each
      participant was administered the Semi-Structured Assessment for the Genetics of
      Alcoholism to assess alcohol dependency and the Family History Assessment module
      to access family history of alcoholism. Xl Test and analysis of variance were
      used to analyze the data. RESULTS: Alcohol dependence was more prevalent among
      men, those with lower income, those with less education, and they utilized mental
      health counseling as opposed to medical-based therapy. Increased reports of
      medical conditions such as migraine (p<.001), loss of consciousness (p=.001), and
      sexually transmitted diseases: (p<.001) were also associated with alcohol
      dependency. Other factors, including visits to inpatient treatment programs, were
      directly related to incidence of alcohol dependency regardless of gender status
      (p<.001). CONCLUSIONS: This study suggests an association exists among alcohol
      dependence, medical conditions, health care, and mental care utilization among
      African Americans. Future research may benefit from investigating if an
      association exists between alcohol use disorders and health care utilization for
      other ethnic groups.

PMID- 23862296
TI  - Racial and ethnic disparities in diabetes complications in the northeastern
      United States: the role of socioeconomic status.
AB  - The role of socioeconomic status (SES) in explaining racial/ ethnic disparities
      in diabetes remains unclear. We investigated disparities in self-reported
      diabetes complications and the role of macro (eg, income, education) and micro
      (eg, owning a home or having a checking account) SES indicators in explaining
      these differences. The sample included individuals with a diagnosis of diabetes
      (N=795) who were aged, on average, 55 years, and 55.6% non-Hispanic white, 25.0%
      African American, and 19.4% Hispanic. Approximately 8% reported nephropathy, 35%
      reported retinopathy, and 16% reported cardiovascular disease. There were
      significant disparities in the rates of complications among non-Hispanic white,
      African American, and Hispanic participants, with Hispanic participants having
      the highest rates of nephropathy, retinopathy, and cardiovascular disease. Macro
      SES indicators (eg, income) mediated racial differences (ie, non-Hispanic whites
      vs African Americans) in self-reported retinopathy, a combination of macro and
      more micro SES indicators (eg, education, income, and ownirg a home or having a
      checking account) mediated racial/ethnic differences (ie, non-Hispanic white vs
      Hispanic participants) in self-reported cardiovascular disease, and only micro
      SES indicators (eg, owning a home or having a checking account) mediated
      differences between lower-income SES racial/ethnic minority groups (ie, African
      American vs Hispanic participants) in self-reported retinopathy and
      cardiovascular disease. Findings underscore that indicators of SES must be
      sensitive to the outcome of interest and the racial/ethnic groups being compared.

PMID- 23862297
TI  - The influence of mistrust, racism, religious participation, and access to care on
      patient satisfaction for African American men: the North Carolina-Louisiana
      Prostate Cancer Project.
AB  - OBJECTIVE: The purpose of this study was to explore whether a particular
      combination of individual characteristics influences patient satisfaction with
      the health care system among a sample of African American men in North Carolina
      with prostate cancer. Patient satisfaction may be relevant for improving African
      American men's use of regular care, thus improving the early detection of
      prostate cancer and attenuating racial disparities in prostate cancer outcomes.
      METHODS: This descriptive correlation study examined relationships of individual
      characteristics that influence patient satisfaction using data from 505 African
      American men from North Carolina, who prospectively enrolled in the North
      Carolina-Louisiana Prostate Cancer Project from September 2004 to November 2007.
      Analyses consisted of univariate statistics, bivariate analysis, and multiple
      regression analysis. RESULTS: The variables selected for the final model were:
      participation in religious activities, mistrust, racism, and perceived access to
      care. In this study, both cultural variables, mistrust (p=<.0001, F=95.58) and
      racism (p=<.002, F=5.59), were significantly negatively associated with patient
      satisfaction and accounted for the majority of the variability represented by
      individual characteristics. CONCLUSION: Mistrust and racism are cultural factors
      that are extremely important and have been negatively associated with patient
      satisfaction and decreased desires to utilize health care services for African
      American men. To overcome barriers in seeking health care services, health care
      providers need to implement a patient-centered approach by creating a clinical
      environment that demonstrates cultural competence and eliminating policies,
      procedures, processes, or personnel that foster mistrust and racism.

PMID- 23862298
TI  - Effect of an eye health education program on older African Americans' eye care
      utilization and attitudes about eye care.
AB  - We examined the impact of an eye health education program for older African
      Americans on attitudes about eye care and utilization, using a randomized trial
      design in a community setting. Participants were older African Americans
      attending activities at senior centers: Ten centers were randomized to an eye
      health education (InCHARGE) or social-contact control presentation. InCHARGE
      addressed the importance of annual dilated comprehensive examination and
      strategies reducing barriers to care. The control presentation was on the
      importance of physical activity. Outcomes were attitudes about eye care 6 months
      post event through questionnaire and eye care utilization during 12 months post
      event through medical record abstraction. At baseline, more than 80% participants
      in both arms said transportation and finding, communicating, and trusting a
      doctor were not problematic and agreed that yearly care was important. One-fourth
      said eye examination cost was problematic; one-half said spectacle cost was
      problematic. There were no group differences 6 months post event. During the 12
      months pre event, the dilated exam rate was similar in the groups (38.3%
      InCHARGE, 40.8% control) and unchanged during the 12 moiths post event. Results
      suggest fewer than half of older African Americans received annual dilated eye
      care. Group-administered eye health education did not increase this rate. Even
      before the program, they had positive attitudes about care, yet many cited
      examination and spectacle cost as problematic, which was not mitigated by health
      education. Evidence-based strategies in a community setting for increasing eye
      care utilization rate in older African Americans have yet to be identified.
      Policy changes may be more appropriate avenues for addressing cost. TRIAL
      REGISTRATION: NCT00591110, www.ClinicalTrials.gov

PMID- 23862299
TI  - Factors associated with nonurgent use of pediatric emergency care among Latino
      families.
AB  - OBJECTIVE: This study investigates Latino parents' decision to seek pediatric
      emergency care for nonurgent health conditions. METHODS: Three focus groups were
      conducted with Spanish-speaking parents. Eligible families had a pediatric
      primary care provider, and their child received emergency treatment for a
      nonurgent health condition in the previous year. Transcripts were transcribed,
      translated, and thematically coded. RESULTS: Parents shared a heightened concern
      about symptoms such as fever or diminished energy. Many related experiences where
      delay resulted in serious illness or death. Other factors included low
      utilization of telephone triage and long clinic wait times. Nearly every family
      had managed the child's illness at home prior to seeking care, employing medical
      and natural remedies. CONCLUSIONS: The study findings suggest that strengthening
      the connection with a child's medical home, eliminating barriers to receiving
      primary care in urgent situations and educating parents about management of
      common illnesses may improve care for Latino children.

PMID- 23862300
TI  - A pilot study to evaluate awareness of and attitudes about prenatal and neonatal
      genetic testing in postpartum African American women.
AB  - OBJECTIVE: A pilot study to determine whether prenatal and neonatal sickle cell
      tests conform to the guidelines established by the American Congress of
      Obstetricians and Gynecologists and the American Academy of Pediatrics. METHODS:
      The project was initially structured as a pair of in-person interviews of
      postpartum women at the University of Chicago, the first collecting medical
      information and the second surveying the ethical, social, and legal implications
      (ELSI) of sickle cell trait (SCT). Due to inadequate enrollment, we elected to
      focus only on the second survey. Descriptive statistics and bivariate analyses
      were performed. RESULTS: A convenience sample was established from 205 women who
      had completed surveys of whom 12 (6%) received no prenatal care. Of the 60 women
      who completed both surveys, 15 (25%) were unsure of their hemoglobinopathy
      status. Of the 50 results we could verify, 2 women (4%) incorrectly recalled
      their hemoglobinopathy status. Of the 193 women who received prenatal care and
      completed the ELSI survey, 47 knew their hemoglobinopathy status from a previous
      pregnancy and 1 had sickle cell disease. Of the remaining 145 women, 53 (37%)
      recalled hemoglobinopathy testing during this pregnancy and 44 (30%) were unsure.
      Only 56 (39%) recalled being told they could refuse testing. Of the 115 women
      whose infants had newborn screening done prior to the interview, only 51 (44%)
      recalled discussions with a pediatric provider. CONCLUSION: Despite professional
      guidelines that stress the importance of education, counseling, and consent for
      prenatal and neonatal testing, postpartum women do not recall these
      conversations.

PMID- 23862301
TI  - Human bites: bloodborne pathogen risk and postexposure follow-up algorithm.
AB  - Human bites may transmit bloodborne pathogens (BPs) by exposing the biter's oral
      mucosa to the bitee's blood and the bite wound to biter's saliva. Consequently,
      bites may require postexposure follow-up per the Occupational Safety and Health
      Administration (OSHA) BP standard. Literature reveals that BP transmission via
      bites is rare. Review of available records in our developmental center identified
      no bite-related BP transmission between 1993 and 2011. To avoid unnecessary
      testing while remaining OSHA-compliant, we propose an algorithm for selective
      follow-up of bites. Since hepatitis B virus can be transmitted by mucosal
      exposure to blood and, rarely, also by nonintact skin exposure to blood-free
      saliva, all biters and bitees require hepatitis B follow-up. Since hepatitis C
      virus and human immunodeficiency virus (HIV) transmissions require "visible
      blood" exposure, and since saliva is usually bloodfree, risk of HCV-HIV
      transmission from biter to bitee is negligible. Therefore biters need HCV-HIV
      testing only after bloody saliva bites. Since biter's oral mucosa invariably gets
      exposed to bitee's blood (reverse exposure), all bitees should be tested for HCV
      HIV infectivity. Our proposed algorithm may prevent harm and waste from
      unnecessary biter testing and venipuncture.

PMID- 23862302
TI  - "Reforming" social security.

PMID- 23862303
TI  - Executive summary of NMA's consensus panel paper on congestive heart failure and
      African Americans.

PMID- 23862304
TI  - Risk factors for domestic violence during pregnancy: a meta-analytic review.
AB  - This article presents the results of a meta-analysis of the existing research
      literature, in an effort to increase our understanding of the prevalence of
      domestic violence (DV) among pregnant women, and of risk factors associated with
      DV during pregnancy. Across 92 independent studies, the average reported
      prevalence of emotional abuse was 28.4%, physical abuse was 13.8%, and sexual
      abuse was 8.0%. Composite odds ratio effect sizes were calculated for the
      demographic, behavioral, and social risk factors identified by 55 independent
      studies. Both victimization and perpetration risk factors were analyzed. Abuse
      before pregnancy and lower education level were found to be strong predictors of
      abuse during pregnancy. Pregnancy being unintended by either the victim or the
      perpetrator, lower socioeconomic status, and being unmarried were found to be
      moderate predictors of abuse during pregnancy.

PMID- 23862306
TI  - Analysis of national empirical data on the characteristics and trends of injury
      among Taiwan's victims of hospitalized child abuse between 1997 and 2009.
AB  - OBJECTIVE: To investigate the characteristics and trends of injury among
      hospitalized child abuse children younger than 18 years between 1997 and 2009.
      METHODS: We selected hospitalized child abuse cases from the Taiwan's National
      Health Insurance (NHI) Database in accordance with ICD-9-CM 995.5x or E967.x.
      RESULTS: There were 1,212 victims of hospitalized child abuse during the research
      period, including 735 boys and 477 girls. The victims were most frequently
      inflicted by the father or stepfather, and the most common injury was
      intracranial damage; besides, the victims most commonly sought treatment in
      medical centers. Infants younger than 1 year accounted for the highest percentage
      of hospitalized victims. Although there were no apparent trends in the overall
      hospitalization rate of the child abuse victims over the 13-year period, the rate
      of abuse among girls increased gradually over the years. CONCLUSIONS: The medical
      staff in hospitals should provide appropriate treatment to the victims and
      contact relevant organizations to intervene; moreover, government agencies should
      formulate effective control measures to develop a safe growth environment for
      children.

PMID- 23862307
TI  - Interpersonal problems and personality features as mediators between attachment
      and intimate partner violence.
AB  - We examined whether hostile dominant interpersonal problems (HDIP), antisocial
      features, and borderline features mediated the relationship between attachment
      (anxiety or avoidance) and intimate partner violence (IPV) with a sample of 132
      male partner abusers. We conducted two path analyses with avoidant attachment as
      the predictor in one model and anxious attachment as the predictor in a second
      model. In both models, HDIP, antisocial features, and borderline features were
      the mediators with IPV as the criterion. For both models, the attachment variable
      had statistically significant path values to the mediating variables. However,
      neither antisocial nor borderline features had statistically significant path
      values from the mediating variable to the criterion variable (IPV). Only HDIP had
      a statistically significant path value from the mediating variable to the
      criterion variable in both models. However, only the avoidant model produced a
      statistically significant specific indirect effect indicating that HDIP clearly
      mediated the relationship between attachment and IPV. Results suggest that
      partner abusive men with predominantly avoidant and, to a lesser degree, anxious
      attachment may be at increased risk for addressing conflicts in a coercive,
      controlling, and vengeful manner that is manifested in physical aggression toward
      a partner. Further, interpersonal constructs may be better measures of
      psychopathology and provide more relevant clinical targets than personality
      constructs with male partner abusers.

PMID- 23862308
TI  - Impulsivity and sexual assault in college men.
AB  - Although impulsivity has been consistently linked to perpetration of sexual
      aggression, results lack clarity because they do not account for the substantial
      heterogeneity associated with the construct. The UPPS-P model (Lynam, Smith,
      Whiteside, & Cyders, 2006), which was proposed to clarify the multidimensional
      nature of impulsivity, has yet to be applied to sexual aggression. We measured
      UPPS-P Impulsivity in a sample of male college students who also self-reported on
      perpetration of sexual aggression. As predicted, impulsivity distinguished
      perpetrators from nonperpetrators. Perpetrators scored higher than non
      perpetrators on Negative Urgency, Positive Urgency, and lack of Premeditation.
      Results suggest that the impulsivity traits most relevant to sexual aggression
      are the tendency to act impulsively when experiencing intense emotions (Positive
      and Negative Urgency) and lack of forethought and planning (lack of
      Premeditation).

PMID- 23862305
TI  - Prevalence and overlap of childhood and adult physical, sexual, and emotional
      abuse: a descriptive analysis of results from the Boston Area Community Health
      (BACH) survey.
AB  - Abuse is associated with a wide variety of health problems, yet comprehensive
      population-based data are scant. Existing literature focuses on a single type of
      abuse, population, or lifestage. Using a racially/ethnically diverse community
      based sample, we document the prevalence of physical, emotional, and sexual abuse
      by lifestage and gender, assess variation in abuse by sociodemographics;
      establish overlap of abuses; and examine childhood abuse relationships with abuse
      in adulthood. Prevalence of abuse ranges from 15% to 27%; women report more
      adulthood emotional abuse and lifetime sexual abuse than men; reports of abuse
      can vary by race/ethnicity and poverty status, particularly in women; there is
      overlap between types of abuse; and a history of childhood abuse is associated
      with a greater risk of abuse as an adult.

PMID- 23862309
TI  - Fear of rape among college women: a social psychological analysis.
AB  - This article examines social psychological underpinnings of fear of rape among
      college women. We analyze data from a survey of 1,905 female undergraduates to
      test the influence of 5 subjective perceptions about vulnerability and harm:
      unique invulnerability, gender risk, defensibility, anticipatory shame, and
      attribution of injury. We include 3 sources of crime exposure in our models: past
      sexual victimization, past noncontact violent victimization, and structural risk
      measured by age, parent's income, and race. Separate measures of fear of stranger
      and acquaintance rape are modeled, including variables tapping current versus
      anticipatory fear, fear on campus versus everywhere, and fear anytime versus at
      night. The data show that fear of rape among college women appears more grounded
      in constructed perceptions of harm and danger than in past violent experiences.

PMID- 23862310
TI  - The cycle of violence: examining the impact of maltreatment early in life on
      adult offending.
AB  - Over the last two decades, considerable scholarly attention has been directed
      toward explaining the "cycle of violence"-a phenomenon whereby victimization and
      offending appear inexorably linked to one another. Extant work has greatly
      contributed to our understanding of this cycle for different types of abuse and
      different types of offending, such as sex offending. The link between sexual
      abuse and later offending cannot be overstated, with research suggesting the
      impact of sexual abuse on sex offending to be more pronounced than any other type
      of abuse. However, in the literature, questions remain regarding sex offenders'
      patterns of offending. Specifically, it remains unclear whether type of abuse
      experienced has a differential impact on type of offending in adulthopd. Using
      retrospective data from sexual offenders in a Canadian penitentiary, we address
      this research gap by examining the impact of abuse experienced during childhood
      and adolescence on various types of offending in adulthood. Results indicate
      partial support for the cycle of violence hypothesis-the extent of criminal
      involvement can be explained as being a consequence of prior maltreatment;
      however, findings also suggest refinements to the theory, because the influence
      of type of abuse varies depending on the type of offending examined. Research and
      policy implications are discussed.

PMID- 23862311
TI  - A revision of the sexual coercion in intimate relationships scale for young
      adults in China.
AB  - The Sexual Coercion in Intimate Relationships Scale (SCIRS; 34 items) assesses
      the severity of sexual coercion (SC) in committed intimate relationships, but it
      does not validly screen out valid target cases or accurately assess prevalence.
      This study aims to revise the SCIRS to facilitate research in China. There were
      927 college students in active dating relationships, from 5 large Chinese cities,
      who participated in the study. The results showed that the revised SCIRS (33
      items) measured 3 constructs-Emotional Manipulation (17 items), Defection Threat
      (7 items), and Violence Threat (7 items)-and that the reliability and validity
      properties were satisfactory. The advantages of the revision and the limitations
      of this study are discussed.

PMID- 23862313
TI  - Adverse childhood experiences, posttraumatic stress disorder symptoms, and
      emotional intelligence in partner aggression.
AB  - Intimate partner violence (IPV) has been linked to childhood abuse, posttraumatic
      stress disorder (PTSD), and low emotional intelligence (EI). Relationships among
      adverse childhood experiences (ACE), PTSD symptoms, and partner aggression (i.e.,
      generalized tendency to aggress toward one's partner) were assessed in 108 male
      IPV offenders. It was hypothesized that ACE is positively correlated with partner
      aggression, PTSD mediates the ACE-aggression relationship, and the ACE-PTSD
      aggression mediation varies by selected EI facets. Results indicate that ACE has
      an indirect effect on partner aggression via PTSD and PTSD mediates the ACE
      aggression link when emotional self-regulation is low and when intuition (vs.
      reason) is high. Trauma-exposed IPV offenders may benefit from comprehensive
      treatments focusing on PTSD symptoms, emotional control, and reasoning skills to
      reduce aggression.

PMID- 23862312
TI  - Adverse pregnancy outcomes and sexual violence among female sex workers who
      inject drugs on the United States-Mexico border.
AB  - This study examines the prevalence of miscarriage/stillbirth among female sex
      workers who inject drugs (FSW-IDUs) and measures its associations with physical
      and sexual violence. Baseline data from 582 FSW-IDUs enrolled in an HIV
      intervention study in Tijuana and Ciudad Juarez, Mexico were used for current
      analyses. 30% of participants had experienced at least one
      miscarriage/stillbirth, 51% had experienced sexual violence, and 49% had
      experienced physical violence. History of miscarriage/stillbirth was associated
      with sexual violence (adjusted odds ratio [aOR] = 1.7, p = .02) but not physical
      violence. Additional reproductive risks associated with miscarriage/stillbirth
      included high numbers of male clients in the previous month (aOR = 1.1 per 30
      clients, p = 0.04), history of abortion (aOR = 3.7, p < .001), and higher number
      of pregnancies (aOR = 1.4 per additional pregnancy, p < .001). Programs and
      research with this population should integrate reproductive health and consider
      gender-based violence.

PMID- 23862314
TI  - Violent victimization among state prison inmates.
AB  - Violent victimization in prison may enhance inmates' cynicism toward legal
      authority and the risk of subsequent criminality. Both micro- and macro-level
      effects on the prevalence and incidence of inmate-on-inmate physical assault
      during a 6-month period were examined for random samples of inmates (n1 = 5,640)
      from all state prisons in Ohio and Kentucky (n2 = 46). Findings revealed that
      nonprovoked assaults were more common among inmates with lifestyles that might
      have increased their vulnerability to victimization (less time spent in
      structured activities, committed violent acts themselves, etc.), and in prisons
      with larger populations and officers who practice lax rule enforcement. A
      supplementary analysis of violent offending also revealed that inmate offenders
      and victims may look less like each other compared to offenders and victims in
      the general population. Policies focused on increasing inmates' involvement in
      structured prison activities, enhancing professionalism among officers, and
      lowering prison populations may be most effective for minimizing the risk of
      violent victimization.

PMID- 23862315
TI  - Risk factors for posttraumatic stress disorder in female help-seeking victims of
      sexual assault.
AB  - Posttraumatic stress disorder (PTSD) is common in the aftermath of rape and other
      sexual assault, but the risk factors leading to PTSD following rape have been
      shown to differ from those related to PTSD following nonsexual assault. This
      prospective study examined risk factors for PTSD severity in 148 female help
      seeking victims of sexual assault. Approximately 70% of the victims experienced
      significant levels of traumatization, with 45% reporting symptoms consistent with
      a probable PTSD diagnosis. Regression analyses showed that relationship with the
      assailant, number of assailants, the nature of the assault, perceived positive
      social support, support satisfaction, feeling let down by others, and prior
      exposure to sexual trauma did not significantly predict PTSD severity at the
      final level of analysis. In accordance with suggestions by Dancu, Riggs, Hearst
      Ikeda, and Shoyer (1996), it is suggested that this is partly caused by a very
      high degree of traumatization in the sample. Instead, previous nonsexual
      traumatic experiences and negative affectivity accounted for 30% of the variance
      in PTSD severity. Although more research is needed on risk factors of assault
      related PTSD, these findings suggest that although sexual assault is associated
      with a high degree of PTSD severity, prior nonsexual victimization and high
      levels of negative affectivity appear to further increase the vulnerability
      toward developing symptoms of assault-related PTSD.

PMID- 23862316
TI  - The satisfaction in teamwork.

PMID- 23862317
TI  - Strength and sustainability.

PMID- 23862318
TI  - Fight for refugee health continues.

PMID- 23862319
TI  - Healing by design.

PMID- 23862320
TI  - Odds ratio.

PMID- 23862321
TI  - Blurred boundaries: double duty caregiving.

PMID- 23862322
TI  - Developmental service workers: New members on the team.

PMID- 23862323
TI  - Collaborative nursing practice: RNs and LPNs working together.

PMID- 23862324
TI  - Hospital nurses' attitudes toward patients with a history of illicit drug use.
AB  - Negative attitudes toward patients with a history of illicit drug use can
      adversely affect the therapeutic nurse-patient relationship, resulting in
      suboptimal patient care. We examined registered nurses' attitudes toward patients
      with illicit drug use (e.g., non-prescription use of opioids and narcotics, use
      of illicit drugs) admitted to the general internal medicine unit of an urban
      hospital and attempted to identify nurse-specific and environmental factors
      influencing these attitudes. The results indicated that nurses had a neutral
      attitude toward working with patients with a history of illicit drug use, but
      respondents also had low motivation and role support (i.e., perception of
      receiving support to fulfil one's professional role) related to caring for this
      high-risk population. The authors suggest greater use of organizational tools,
      such as protocols, consult services and in-services, to address nurses' clinical
      concerns and support therapeutic nurse-patient relationships and thereby enhance
      care delivery.

PMID- 23862325
TI  - Health coaching a natural fit.

PMID- 23862326
TI  - Baby friendly.

PMID- 23862327
TI  - Supporting sexual activity and intimacy in care facilities.

PMID- 23862328
TI  - Not wasted time in aged care placement.

PMID- 23862329
TI  - Renewable energy needs community consultation.

PMID- 23862330
TI  - Put your safety first.

PMID- 23862332
TI  - May Day March.

PMID- 23862331
TI  - Needlestick and sharps injuries are preventable.

PMID- 23862333
TI  - Advanced care directives: an update.

PMID- 23862334
TI  - ANF online training rooms.

PMID- 23862335
TI  - Patient privacy: so easily breached.

PMID- 23862336
TI  - The vitamin D dilemma.

PMID- 23862337
TI  - Emerging data on resettled Iraqi refugees in Australia: 10 years after the 2003
      Iraq conflict.

PMID- 23862338
TI  - Audiometry nursing: a career.

PMID- 23862339
TI  - Primary health care nursing: at the crossroads.

PMID- 23862340
TI  - Tackling the workforce shortage.

PMID- 23862342
TI  - Meeting the sexual health care needs of young refugee women.

PMID- 23862341
TI  - Leadership and management in advanced nursing in general practice.

PMID- 23862343
TI  - Australia's first mental health nursing charity: ROAM communities.

PMID- 23862344
TI  - Special patient education needs of the elderly.

PMID- 23862345
TI  - Supporting our senior citizens in their own homes.

PMID- 23862346
TI  - Legislating for choice.

PMID- 23862347
TI  - "Don't ignore severe impact of staffing cuts".

PMID- 23862348
TI  - Trusts desire new squeeze on pay.

PMID- 23862349
TI  - BME applicants less likely to win NHS jobs.

PMID- 23862350
TI  - The nursing voice is stronger after NHS reforms, insists CNO.

PMID- 23862351
TI  - Nurse values test among tasks handed to new education body.

PMID- 23862352
TI  - "We have refined our strategy following the Francis report".

PMID- 23862353
TI  - "Many issues must be tackled to move care into the community".

PMID- 23862354
TI  - Preventing the spread of HIV infection.
AB  - Approximately 96,000 people are living with HIV in the UK, a quarter of whom are
      unaware they are infected. While in some parts of the world the number of people
      newly infected with HIV has fallen, in the UK in 2011 there was a rise in the
      number of men who have sex with men being diagnosed. HIV prevention strategies
      are a public health priority, while ongoing research into HIV testing in all
      clinical settings remains a priority. This article explores preventive measures
      that can be used to reduce the spread of HIV and offers advice on how nurses can
      contribute to these.

PMID- 23862355
TI  - Identify needs of women living with HIV.
AB  - This article reports on the development of the Between the Sheets project for
      women living with HIV. It began with an event that provided a forum to address
      their unmet needs concerning sexual activity and related issues. Development was
      informed by a focus group of women with HIV, some of whom also presented their
      personal stories. Attendees' evaluations have identified further unmet needs and
      ways HIV services might adapt to better meet the needs of these individuals.

PMID- 23862356
TI  - Framework for improving sexual health outcomes.

PMID- 23862357
TI  - Principles of monitoring postoperative patients.
AB  - Postoperative care is provided by perioperative nurses. They are often
      experienced in a specialised area of surgery that requires specific care for the
      intervention performed. This article, the first in a two-part series, identifies
      the principles of postoperative nursing care. These remain reasonably consistent
      over the years but nurses must ensure they keep up to date with guidelines,
      policies and evidence-based practice.

PMID- 23862358
TI  - End-of-life care for people dying from cardiovascular diseases.

PMID- 23862359
TI  - More personal palliative care.

PMID- 23862360
TI  - Getting the best from your staff.

PMID- 23862361
TI  - Not for the faint-hearted.

PMID- 23862362
TI  - Making it "just happen".

PMID- 23862363
TI  - St. Paul-Syria connection.

PMID- 23862364
TI  - Learning by the light of the moon.

PMID- 23862365
TI  - What they don't teach in medical school.

PMID- 23862366
TI  - Programs that can help you pay it back--and pay it forward.

PMID- 23862367
TI  - 10 thrigs to consider in a physician employment agreement.

PMID- 23862368
TI  - Practicing medicine in an imperfect world. Five truths about preventing or
      surviving a lawsuit.

PMID- 23862369
TI  - Five secrets to financial success for young physicians.

PMID- 23862370
TI  - A case for professional community doctors.

PMID- 23862371
TI  - The 2013 session.

PMID- 23862372
TI  - MMA scores with MERC at Legislature.

PMID- 23862373
TI  - Management of bloodless surgery in a trauma setting. Balancing patient wishes
      with safety.
AB  - Many patients refuse blood or blood products because of religious beliefs or fear
      of complications. At Hennepin County Medical Center, a multidisciplinary team
      developed a Bloodless Surgery Medicine Guideline (BSMG) to help identify those
      who refuse blood products, guide medical decision-making, improve documentation
      of informed consent or refusal, and ensure continuity of care for patients. To
      our knowledge, this is the first documentation of a guideline for managing
      informed consent for or refusal of blood or blood products in trauma patients.
      This article discusses the development of and legal rationale for two key
      components of the BSMG: an informed consent/refusal algorithm and a blueprint for
      discussing the use of blood or blood components with patients and documenting
      their decisions.

PMID- 23862375
TI  - Lessons I learned from a dying friend.

PMID- 23862374
TI  - Hospice in the United states expands, evolves over 30 years--a data review.

PMID- 23862376
TI  - Life's final journey...

PMID- 23862378
TI  - "Purple" your customers.

PMID- 23862377
TI  - Efforts to change hospice's payment formula intensify.

PMID- 23862379
TI  - Notes from nonprofits: living life on your terms.

PMID- 23862380
TI  - Becoming an Alzheimer's Whisperer through activities (part 2).

PMID- 23862381
TI  - We are all losing it.

PMID- 23862382
TI  - Heaven can wait--but can we?

PMID- 23862383
TI  - [Regulation of osteogenic differentiation of mesenchimal stem sells of bone
      marrow].
AB  - The review describes the mechanisms of hormonal, autocrine, paracrine and
      intracellular regulation in osteogenic differentiation of mesenchymal stem cells,
      the role of negative feedbacks in this process.

PMID- 23862384
TI  - [Protein kinases role in adaptive phenomenon of heart ischemic postconditioning
      development].
AB  - Authors submitted an analysis of papers given up an involvement of protein
      kinases in heart ischemic postconditioning. This analysis of literature source
      allowed to authors affirms that signaling system of postconditioning can involve
      kinases: PKC, PI3K, Akt, MEKl/2, ERK1/2, MTOR, p70s6K, GSK3b, PKG and also eNOS,
      NO, GC, motoKATP channel, ROS, MPT pore. At the same time it is unclear a real
      contributions of kinases mTOR, p70s6, AMPK and GSK3b in the mechanism of infarct
      limiting impact of postconditioning. It is required a further study of the chain
      of signaling events following JAK2 and p38 kinase activation. The knowledge of
      Ras and Raf-1 role in postconditioning has hypothetical character. The tyrosine
      kinase significance in postcondi-tioning is unclear, particular Src kinase, which
      plays an important role in the regulation of cardiac tolerance to an impact of
      ischemia and reperfusion.

PMID- 23862385
TI  - [Effect of propofol on functional response of neuronal population in cat primary
      visual cortex].
AB  - The impact of system anesthetic propofol on strength of functional response was
      investigated in population of primary visual cortex neurons. Elaborated protocol
      of anesthesia allowed appropriate depth of anesthesia and artifact free
      experimental data recording. At the start of experiment optical access to the
      surface of cortex was provided. Propofol was used as main general anesthetic.
      Control of anesthesia depth was carried out by monitoring of physiological
      parameters. Effect ofpropofol on functional response was evaluated by intrinsic
      optical imaging. Stability of neuronal response was estimated during whole
      experiment and after single injection ofpropofol. It was shown that extended
      administration ofpropofol do not have negative influence on strength of recorded
      neuronal signal. At the same time bolus of propofol depresses amplitude of
      response. Practical recommendations are suggested for conduction of longitudinal
      neurophysiological experiments using propofol as main anesthetic.

PMID- 23862386
TI  - [Features of spatial orientation formation in posterity of female rats with liver
      experimental defeat in Morris water maze].
AB  - It was established, that the chronic experimental hepatobiliary systems alcohol
      induced pathology of female rats caused infringement of spatial differentiation
      development in their posterity in Morris water maze. In experimental infant rats
      it was revealed the increase of time of platform fin ding in a water Morris task,
      lengths of trajectory of movement, increase of time of stay near walls
      (thigmotaxis) and speed of movement reduction, the latent period of zones of
      start leaving and efficiency of way index.

PMID- 23862387
TI  - [The effects of selective 5HT3 receptor blockade on physiological markers of
      abdominal pain in awake dogs].
AB  - In awake dogs, the visceromotor and cardioautonomic responses to the rectal
      balloon distension were studied before and after intravenous administration of a
      selective 5HT3 receptor antagonist granisetron. It was shown that balloon
      distension level up to 60 mmHg caused neither noticeable muscle responses nor
      substantial changes in heart rate. In turn, distending pressures of 80 mmHg and
      higher induced vigorous abdominal muscle contractions and tachycardia that were
      graded with increasing intensities of stimulation. Thus, the rectal stimulation
      with pressures 80 mmHg and more produced the changes in visceromotor and
      cardiovascular indices which could be considered as suitable indicators of
      visceral nociception in conscious animals. Based on monitoring of these
      physiological markers in a model of abdominal pain the dose-dependent
      antinociceptive effect of granisetron in awake dogs has been demonstrated for the
      first time. It was determined that granisetron in doses of 0.25, 0.5 or 1.0 mg/kg
      induced correspondingly 33.6 +/- 9.2, 58.0+/- 8.6 [see text] 76.7 +/- 5.5 %
      decrease in visceromotor response of dogs to nociceptive visceral stimulation.
      The effect occurred immediately after the drug administration and was lasting
      more than 90 min. In turn, the dose-dependent suppression of the rectal
      distension-induced tachycardia was less prominent and only observed during the
      initial period of granisetron action. The described model of abdominal pain in
      awake dogs might be useful for preclinical screening of new pharmacological
      substances, whereas the obtained data could contribute to the development of more
      efficient analgesics aimed in patients with irritable bowel syndrome.

PMID- 23862388
TI  - [Influence of agonist and antagonist Nalpha7-cholinoreceptors on active avoidance
      learning and gonadal hormones levels in ovariectomized female rats].
AB  - The aim of this work was to study the influence of co-administration of agonist
      and antagonist of Nalpha7-cholinoreceptors with low dose of 17beta-estradiol on
      dynamics of acquisition and retention in active avoidance test, on the behavior
      in the "open field" test, as well as tropic and gonadal hormones levels in
      ovariectomiczed female rats. Antagonist of Nalpha7-cholinoreceptors - RJR-2403
      (1.0 mg/kg, i. p.) and antagonist of Nalpha7-cholinoreceptors - mecamylamine (1.0
      mg/kg, i. p.) were administered chronically (14 days) isolated or in combination
      with low dose of 17beta-estradiol (0.5 m/rat, s. c.) to ovariectomized rats. It
      was revealed that RJR-2403 in combination with low dose of 17beta -estradiol
      completely restored impairments in mechanisms of dynamics of active avoidance
      performance and increased exploratory and grooming behavior in the "open field"
      test in ovariectomized rats. Moreover, RJR-2403 treatment decreased follitropine
      and lutropine levels and increased estradiol level in the blood serum in
      ovariectomized rats. Administration ofmecamylamine alone or in combination with
      low dose of 17beta-estradiol in ovariectomiczed rats failed to influence on
      dynamics of passive avoidance learning and failed to modify behavior in the "open
      field" test. The results of the present study suggest positive effect of Nalpha7
      cholinoreceptors stimulation on background of low dose for 17beta-estradiol on
      active avoidance learning and tropic and gonadal hormones levels at estrogen
      deficiency.

PMID- 23862389
TI  - [Dynamics of initial manifestations of experimental diabetic encephalopathy].
AB  - We established that alloxan diabetes leads to early development of diabetic
      encephalopathy on the background of marked hyperglycemia. Initial manifestations
      of experimental diabetic encephalopathy are based on fast progressing loss of
      neurons and glial cells in the structures of primary somatosensory cortex (field
      Par 1) and hippocampus (field CAl) between 4th and 17th day after alloxan
      administration. This is accompanied by accumulation oflipofuscin in neocortex
      neurons. Manifestations of diabetic encephalopathy on diencephalic level is
      registered only 10 days after alloxan administration, specifically in
      paraventricular nucleus where decrease in the number of neurocytes is observed
      between 10th and 17th day after diabetes induction. Initial manifestations of
      experimental diabetic encephalopathy correspond to progressing inhibition of
      orientation and exploratory behavior in animals and decrease of their capacity
      for conditioning.

PMID- 23862390
TI  - [The pulmonary hemodynamics changes following experimental myocardial ischemia in
      rabbits with decreased arterial pressure].
AB  - In acute experiments in rabbits the changes of the pulmonary hemodynamics
      following myocardial ischemia in the region of the descendent left coronary
      artery were studied in normotensive animals and after the infusion of histamine
      or isoproterenol. Following histamine intravenous in fusion the pulmonary artery
      pressure and pulmonary vascular resistance were increased, however the pulmonary
      artery flow decreased. In these conditions myocardial ischemia caused the
      returning of the elevated pulmonary artery pressure to normal level following the
      diminishing of the pulmonary artery flow to the same level as in normotensive
      rabbits. Meanwhile the pulmonary vascular resistance remained elevated. Following
      isoproterenol intravenous injection the isoproterenol artery pressured and flow,
      pulmonary vascular resistance were decreased. In these conditions myocardial
      ischemia caused the decrease of the isoproterenol artert pressure, more, than in
      normotensive rabbits, which was the result of diminishing left atrial pressure,
      however, the pulmonary artery flow and pulmonary vascular resistance decreased in
      both cases to the same level. Thus we concluded, that following myocardial
      ischemia in rabbits with decreased arterial pressure, the changes of pulmonary
      artery pressure depend on pulmonary artery flow and left atrial pressure changes.
      The shifts of the pulmonary artery flow depend on venous return ones and does not
      correlated with pulmonary vascular resistance changes.

PMID- 23862391
TI  - [The ratio between the initial stages of assimilation of intact and hydrolyzed
      dipeptides in rat small intestine].
AB  - Absorption of amino acids and dipeptides in the intestine may be coupled with
      sodium or proton, respectively. In both cases, when these nutrients are added to
      the mucosal solution (solution bathing the mucosa) through the epithelial layer
      should flow additional electric current. which is the most convenient to register
      by the short-circuit current method (SCC). It was shown that at pH 8.5, we can
      observe more efficient dipeptide transport (SCC response amplitudes on dipeptides
      have greater amplitude then SCC responses to equimolar mixture of the
      corresponding amino acid). In contrast, at pH 5.5 we observe the reverse
      situation - the SCC responses to mixture of amino acids are more then SCC
      responses to dipeptides. Increased with pH sodium dependent component of the
      stimulating effect of easily hydrolysable dipeptides is due to the membrane
      digestion. Sodium independent effect of dipeptides assimilation decreasing with
      pH caused by, apparently, functioning of proton-dependent transporter PepT1 for
      oligopeptides in the apical membrane of enterocytes. We believe that sequential
      "conditioning" of the stomach contents in the ever-increasing pH while its moving
      along the gastrointestinal tract (from stomach to colon) enables optimal use of
      both the mechanism of absorption of oligodipeptides, which is accompanied by a
      more complete digestion of oligodipeptides.

PMID- 23862392
TI  - [Involvement of Akt in regulation of skeletal muscle metabolism].
AB  - The enzyme Akt 1 is a member of serine/threonine specific protein kinases family.
      Akt plays an important role in the transmission of extracellular signals and
      mechanical stimuli via phosphorylation of its numerous substrates involved in
      anabolic and catabolic processes as well as mechanical responses of skeletal
      muscle. Expression of the Akt is increased during skeletal muscle hypertrophy and
      decreased during muscle atrophy. The G205T polymorphism of Akt is associated with
      transcriptional activity of the gene in muscle cells and, respectively, with
      skeletal muscle phenotypes.

PMID- 23862393
TI  - [Tear fluid proteome variability in healthy donors].
AB  - The variability of control samples is the main problem in clinical proteomics and
      reliable sources for estimation of variability of normal content of different
      proteins are not numerous. Most of the investigations of normal human tear
      proteome include pool of samples as reference materials. But it is impossible to
      use such experimental approach to establish the range of variability of different
      tear proteome components. This study is the first attempt to estimate the
      variability of proteins content in healthy donors tear using high-performance
      liquid chromatography and tandem mass spectrometry. The protein profiles from 11
      individual healthy donors were analyzed. Essential variability of the minor
      proteins was revealed while the presence of 6 major proteins in all 11 samples
      was invariable. We found the Lacritin glycosylation in all samples of tear fluid
      received from healthy donors. It seems that this modification is typical for
      healthy donors tear. The analysis of the pool samples was also carried out to
      estimate the availability for this approach for the search of ophthalmologic
      diseases biomarkers.

PMID- 23862394
TI  - Focus on work-related asthma.
AB  - Work-related asthma, encompassing both occupational asthma and work-exacerbated
      asthma, accounts for 10%-25% of adult asthma in Europe and occupational asthma is
      currently one of the most common forms of occupational lung disease in many
      industrialized countries. It is cause of direct and indirect costs for the
      worker, the employer and the society and it is probably still underdiagnosed.
      Hence, the possibility of work-related asthma should be considered in all adult
      patients in whom asthma started or worsened during their working life. The
      investigation of WRA includes assessing the presence of asthma, and demonstrating
      its work-relatedness, that requires training and expertise. Due to the frequent
      association of occupational asthma and rhinitis, the expertise. Due to the
      frequent association of occupational asthma and rhinitis, the presence of both
      upper and lower airway symptoms should be investigated. Furthermore, since is
      work-related asthma is a preventable disease all efforts should be made for
      effective prevention strategies.

PMID- 23862395
TI  - Environmental interventions for mite-induced asthma: a journey between systematic
      reviews, contrasting evidence and clinical practice.
AB  - House dust mites (HDM) are one of the most important sources of indoor allergens
      worldwide. Exposure to high environmental levels of dust mite allergen is
      associated with an increased risk of sensitization, asthma and deterioration of
      lung function. On the basis of these data, it would be logical to assume that
      asthmatic patients with mite allergy could benefit from a reduction of exposure
      to these allergens. Several environmental prophylactic actions against HDM,
      either physical or chemical have been tried, alone or in different combinations.
      However, a recent Cochrane Systematic Review did not detect specific clinical
      benefits from the use of prophylactic environmental measures in asthmatic
      patients sensitive to HDM and concluded that such measures can no longer be
      recommended as they are ineffective. This paper presents the results of a web
      based questionnaire, administered to more than 200 Italian paediatricians, and
      shows that physicians' behaviour in real life is very far from SR conclusions. It
      also summarizes the indications of the most authoritative guidelines,
      highlighting some contrasting evidence and some significant weaknesses of the SR,
      that could make the final conclusions at least uncertain. In the light of these
      findings, it seems that the recent Cochrane SR cannot be considered the
      definitive document on the uselessness of environmental prevention of mite
      related asthma.

PMID- 23862396
TI  - Safety of cluster specific immunotherapy with a modified high-dose house dust
      mite extract.
AB  - INTRODUCTION: Although the efficacy and safety of high dose hypoallergenic mite
      subcutaneous immunotherapy (SCIT) using a conventional administration schedule
      has already been demonstrated, there is no reported experience on the safety of
      these extracts with cluster schedules. We wanted to determine whether the use of
      a cluster schedule of a hypoallergenic allergen with a high concentration of
      house dust mite allergens commonly used in normal practice was safe and well
      tolerated in patients with dust mite allergy. MATERIAL AND METHODS: Multicentre,
      observational, retrospective study of dust mite allergic patients treated with a
      cluster schedule of SCIT (Acaroid; Day 1: 300/300 therapeutic units, TU--Day 8:
      1000/1000 TU--Day 15: 3000/3000 TU) in 23 Spanish sites. RESULTS: Cluster
      schedule was used on 434 patients (40.1% children), with a total of 3256 doses
      (38.2% in children). There were 88 clinically relevant adverse reactions, 79 out
      of them local and 9 systemic (but mild-moderate) that amounted to 2.7% of all the
      administered doses. All the patients fulfilled the cluster schedule. CONCLUSIONS:
      Cluster schedule with high dose hypoallergenic mite-SCIT was safe and well
      tolerated in routine clinical practice. Therefore, its use could reduce the costs
      and time needed to achieve the desired maintenance dose and increase compliance.

PMID- 23862397
TI  - Occupational asthma associated to the exposure to limonium tataricum flowers.
AB  - Limonium tataricum (Lt) is a plant belonging to the family of Plumbaginaceae. The
      role of this family and in particular, that of dried flowers (but not of the
      pollen) in occupational allergy has already been described. We have observed a
      farmer with asthma occurring in the presence of fresh flowers. Standard
      methacoline test demonstrated that the patient was a true asthmatic. The
      allergenicity of Lt pollen was thus investigated Skin prick tests (SPT) were
      carried out using both standard allergens and the Lt extract and the patient's
      mucosal reactivity was evaluated by nasal provocation test with the pollen
      extract. In vitro studies were also performed on the patient's serum by
      evaluating routine specific anti-allergen IgE on raw extracts and on Microarray
      Allergen Chip (ISAC). Finally, the raw extract of the fresh Lt pollen was also
      used in ELISA inhibition test, immunoblotting and Basophil Activation Test (BAT).
      The specific sensitization was demonstrated by Skin Prick test and nasal
      provocation test. The sensitization was also confirmed by specific IgE and by in
      vitro activation of basophils in the presence of the pollen. By using RAST
      inhibition test, the presence of cross-reactivity with other pollens was ruled
      out. According to our results, Lt extracts contain an allergenic activity not
      only as dried flowers, but also as fresh pollen. For its role in occupational
      asthma, this allergen should be included in any allergy screening at least in
      farmers or in the flower industry employers.

PMID- 23862398
TI  - Assessment of asthma control: clinical, functional and inflammatory aspects.
AB  - BACKGROUND: Asthma is a complex disease with numerous markers of
      severity/activity. Clinical assessment,functional parameters and inflammation
      biomarkers are the most used A correlation between them is difficult, as each one
      evaluates a particular aspect of the disease. OBJECTIVE AND METHODS: To explore
      the possible association between asthma control, pulmonary function and
      inflammation in patients with asthma, consecutive asthmatics underwent
      simultaneous spirometry (measurement of FEV1), exhaled nitric oxide (eNO)
      evaluation and Asthma Control Test (ACTTM) questionnaire. RESULTS: The study
      included 232 asthmatics (mean age: 37.48 years; 78.4%female): 43% had
      uncontrolled asthma (ACTTM < or = 19) with FEV1 mean values of 83.3% +/- 21.8;
      48% partially controlled (ACTTM: 20-24) with FEV1 of 87.6% +/- 17; 9% complete
      control (ACTTM = 25) with FEV1 of 93.1 +/- 20.6. The relation ACTTM/FEV1 and
      ACTTM/FEF 25-75% was statistically significant (p = 0.001 and p = 0.034,
      respectively). Among patients with eNO < 35 ppb, 66% had FEV1 > 80% and 52% had
      ACTTM > 19. No association was found combining ACTTM/eNO or FEV1/eNO. A subgroup
      of 66 patients was evaluated twice. CONCLUSION: An association was found between
      ACTTM and spirometry, with higher ACTTM scores reflecting less bronchial
      obstruction. The authors advise a combined approach in asthma follow-up,
      involving clinical aspects, functional parameters and inflammation biomarkers,
      although in some circumstances ACT could be a valid instrument to be used alone
      to assess control.

PMID- 23862399
TI  - Allergen sensitizations in southern Italy: a 5-year retrospective study in
      allergic respiratory patients.
AB  - The assessment of the distribution of allergen skin test sensitizations is highly
      recommended for the optimal management of allergic respiratory conditions. We
      aimed at evaluating the distribution of allergen sensitizations in individuals
      with asthma and/or rhinitis in the Southern region of ltaly, and at exploring
      whether changes in the frequency of allergen sensitizations occurred after a 5
      year period. Demographic data and skin prick test sensitizations to allergens
      from asthmatics and/or rhinitis attending the Division of Respiratory Diseases,
      University of Palermo, Italy in 2005 (Phase 1) and in 2010 (Phase 2) were
      extrapolated and retained for analysis. A total of 2033 allergic respiratory
      patients were included (1002 in Phase 1 and 1031 in Phase 2). In both
      investigations, the most prevalent allergen sensitization was towards Parietaria;
      however, a significant reduction in the rate of prevalence after 5 years was
      recorded (from 60% to 48% of skin test positive patients, p < 0.0001). Up to one
      out of two subjects showed sensitization to dust mites in both Phases.
      Interestingly, Cypress pollen sensitization almost doubled from Phase 1 (17%) to
      Phase 2 (29%; p < 0.0001). Overall, the mean number of skin test sensitizations
      for each patient increased from 2.7 +/- 1.6 in Phase 1 to 3.1 + 1.8 in Phase 2 (p
      < 0.0001). The present findings confirm the prevalent role of Parietaria
      sensitization in the allergic population of the Mediterranean area of Southern
      Italy, and document the increase of Cypress sensitization. These observations
      could contribute to a proper management of chronic allergic respiratory
      conditions in this region.

PMID- 23862400
TI  - Effect of sodium hyaluronate on mucociliary clearance after functional endoscopic
      sinus surgery.
AB  - BACKGROUND: To determine the effect of intranasal sodium hyaluronate on
      mucociliary clearance time following functional endoscopic sinus surgery in
      patients with nasal polyposis. STUDY DESIGN: Randomized, controlled, blinded
      study. METHODS: Thirty-six patients with grade II nasal polyposis undergoing
      functional endoscopic sinus surgery received intranasal sodium hyaluronate 9 mg
      twice daily or saline for 30 days commencing on the second day after surgery.
      Ciliary mucous transport time was assessed using charcoal powder and saccharin
      administered during rhinoscopy. Other outcomes included changes in symptoms,
      endoscopic appearance of the nasal mucosa, and tolerability. RESULTS: Patients
      receiving sodium hyaluronate had a significantly faster mucociliary clearance
      time at 1 month compared with controls (14.3 +/- 2.5 vs. 23.6 +/- 3.3 minutes; p
      = 0.000). Furthermore, sodium hyaluronate recipients experienced a lower
      incidence of rhinorrhea, less nasal obstruction and a lower incidence of exudate
      on endoscopy than control subjects at 1 month (all p < 0.05). Sodium hyaluronate
      was well tolerated in patients following functional endoscopic sinus surgery.
      CONCLUSION: The use of intranasal sodium hyaluronate in patients undergoing
      functional endoscopic sinus surgery for nasal polyposis augmented the improvement
      in mucociliary clearance observed following this procedure and improved several
      clinical and endoscopic parameters. These data provide encouraging evidence of
      the beneficial effects of sodium hyaluronate in the care of patients undergoing
      functional endoscopic sinus surgery with which to continue the development of the
      product for this indication.

PMID- 23862401
TI  - Atopic dermatitis induced by systemic immunosupression with tacrolimus--case
      report.
AB  - Type I hypersensitivity reactions have been described after solid organ
      transplantation despite T cell targeted immunosuppressive therapy. There are
      several reports of food allergy, asthma and eosinophilic colitis in pediatric
      transplant recipients under Tacrolimus immunosuppression, but not Cyclosporine A.
      We present the case of a 6 year old patient that developed de novo atopic
      dermatitis, eosinophilia and high levels of total IgE under systemic treatment
      with tacrolimus.

PMID- 23862402
TI  - Penile granulomatosis presenting as pseudoangioedema.
AB  - Many conditions may present as angioedema. We report a case of a 46 year-old man
      presenting with intermittent episodes of penile swelling. Following a series of
      investigations, he was diagnosed with genital granulomatosis. Ano-genital
      granulomatosis is a rare chronic inflammatory condition and that can present as
      diffuse penile, scrotal, vulvar or ano-perineal swelling with non-caseating non
      necrotising granulomas on histology.

PMID- 23862403
TI  - Repeated anaphylactic episodes to orange and apple.
AB  - This study reports an unusual case of repeated anaphylactic episodes to orange
      and apple without clinical evidence of primary sensitization to peach LTP. In
      vitro and in vivo tests revealed heat stability of the implicated allergens and
      also provided new evidence of differences in allergenicity among apple varieties
      and strong cross reactivity of citrus fruits. "Prick-to-prick" method with fresh
      fruits proved to be a quick and advantageous tool in investigating allergy to
      fresh fruits.

PMID- 23862404
TI  - A relapse of near-fatal thunderstorm-asthma in pregnancy.
AB  - Thunderstorm-related asthma is a dramatic example of the allergenic potential of
      pollen antigens. Pollen allergic patients who encounter the allergenic cloud of
      pollen during a thunderstorm are at higher risk of having an asthma attack.
      Relapse is also possible and we describe here the first case of relapse of near
      fatal thunderstorm-asthma occurred in a 36 years old, 20 weeks pregnant woman
      affected by seasonal asthma and sensitized to allergens released by
      Parietariapollen. Patients suffering from pollen allergy should be alerted of the
      danger of being outdoors during a thunderstorm in the pollen season and if they
      experienced an episode of severe thunderstorm-related asthma could be at risk of
      a relapse during a heavy precipitation event.

PMID- 23862405
TI  - Luminescent magnetic quantum dots for in vitro/in vivo imaging and applications
      in therapeutics.
AB  - The quest for design of newer/advanced methods for medical diagnosis and targeted
      therapeutics are of utmost interest and challenging too, because of its
      importance in clinical diagnosis. Currently available diagnosis methodologies
      have their own disadvantages. These shortcomings can be overcome by using
      multimodal imaging systems where two or more imaging modalities may be coupled.
      Nanoparticles being widely studied for targeted drug delivery and as biological
      contrasting agents, might play a decisive role in such findings. This review is
      focused towards the ongoing research in the area of hybrid nanocomposites which
      can be used for both as MRI contrasting agent (magnetic nanoparticles) and
      molecular imaging studies (using fluorescent quantum dots) at in vitro and in
      vivo level. Though several reports are available in literature for such bimodal
      imaging systems, their clinical trials are very restricted, possibly because of
      the lack of communication between the in vitro and in vivo studies. This review
      is expected to bridge the gap between such studies.

PMID- 23862406
TI  - Zinc oxide nanoparticles induce rat retinal ganglion cell damage through bcl-2,
      caspase-9 and caspase-12 pathways.
AB  - Nanomaterials, including zinc oxide (ZnO) nanoparticles, are being developed for
      a variety of commercial products. Recent reports showed that cells exposed to ZnO
      nanoparticles produced severe cytotoxicity accompanied by oxidative stress and
      genotoxicity. To understand the possible mechanism underlying oxidative stress of
      ZnO nanoparticles, the present investigation focused on the direct bioactivity of
      ZnO nanoparticles using a rat retinal ganglion cell (RGC-5) culture. At
      concentrations relevant to those used in vitro exposure of RGC-5 cells to ZnO
      nanoparticles, it was found that ZnO nanoparticles could inhibit cell
      proliferation in time- and concentration-dependent manners. Meanwhile, cell cycle
      arrest of S and G2/M phases occurred in RGC-5 cells induced by ZnO nanoparticles.
      Moreover, our results also demonstrated that the overproduction of reactive
      oxygen species (ROS) and elevated level of caspase-12 as well as decreased levels
      of bcl-2 and caspase-9 occurred after treatment with different concentrations of
      ZnO nanoparticles when compared to those in untreated cells. In summary, our
      findings suggest that ZnO nanoparticles could lead to the over generations of ROS
      and caspase-12 as well as decreased levels of bcl-2 and caspase-9. These results
      indicate that bcl-2, caspase-9 and caspase-12 may play significant roles in ZnO
      nanoparticle-induced RGC-5 cell damage.

PMID- 23862407
TI  - Poly(lactic-co-glycolic acid) encapsulated gadolinium oxide nanoparticles for MRI
      based cell tracking.
AB  - Superparamagnetic iron oxide particles have proven useful for cell tracking
      applications by monitoring cell transplantation and migration in living
      organisms. However, one perceived drawback is that these particles cause dark
      contrast in MRI, sometimes yielding confusion with other biological phenomena,
      which also yield dark contrast. To that end, researchers have investigated the
      use of gadolinium oxide (Gd2O3) based contrast agents for MRI-based cell
      tracking, as Gd2O3 has favorable r1 molar relaxivity. We synthesized Gd2O3
      nanocrystals and encapsulated them within PLGA matrices to form approximatley to
      150 nm nanoparticles. r1 was 1.9 mM(-1) sec(-1) and r2 was 8.4 mM(-1) sec(-1).
      Cell labeling with particles was well tolerated by cells except at very high
      doses. MRI of labeled cells showed that labeled cells could achieve both R1 and
      R2 enhancements due to the internalized particles. R2 enhancements were
      approximately to twice that of R1 enhancements suggesting the use of very short
      echo times when using Gd2O3 based contrast agents for MRI-based cell tracking.

PMID- 23862408
TI  - A comparative study of the photothermal efficiency of electrically conducting
      poly(3,4-ethylenedioxythiophene)-based nanomaterials with cancer cells.
AB  - The photothermal efficiency of two similar organic nanomaterials, poly(3,4
      ethylenedioxythiophene):poly(4-styrene-sulfonate) (PEDOT:PSS) nanoparticles and
      poly(3,4-ethylenedioxythiophene) (PEDOT) nanotubes, are compared. The PEDOT:PSS
      nanoparticles ranged from 100-200 nm in diameter, while the PEDOT nanotubes
      ranged from 200-400 nm in diameter and 4-10 microm in length. By changing the
      aspect ratio of the PEDOT nanomaterials from a spherical to a tubular shape,
      interesting differences in the optical and electronic properties of the materials
      were realized. Because of this, the PEDOT nanotubes were shown to generate on
      average approximately to 10 degrees C better internal heating for similar
      concentrations compared to the PEDOT:PSS nanoparticles. Cytotoxicity studies of
      both nanomaterials showed no significant toxicity towards RKO or HCT116
      colorectal cancer cells in the absence of NIR light. The NIR-mediated
      photothermal efficiency of the PEDOT:PSS nanoparticles and the PEDOT nanotubes
      were compared in-vitro. A cell viability assay was performed and at the highest
      concentration (0.1 mg/mL) of nanomaterial, cell survival was close to 20% for the
      PEDOT:PSS nanoparticles with both RKO and HCT116 cells. Consequently, cell
      survival for the PEDOT nanotubes was less than 5% for both RKO and HCT116 cells.
      An in-vitro three dimensional tumor model was assembled using collagen gel tissue
      phantoms. The depth of heat penetration from the PEDOT nanotubes into the tissue
      phantoms, along with cell viability of RKO and HCT116 cells was determined and
      quantified.

PMID- 23862409
TI  - Fluorogenic pH-sensitive polydiacetylene (PDA) liposomes as a drug carrier.
AB  - A crucial issue for current liposomal carriers in clinical applications is the
      sustained-release property of the encapsulated drugs. We have developed novel
      fluorogenic pH-sensitive polymerized liposomes composed of polydiacetylene (PDA)
      lipids and other types of lipids. Unilamellar liposomes containing 10,12
      pentacosadiynoic acid (PCDA), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine
      (DOPE), and N-palmitoyl homocysteine (PHC) were loaded with ampicillin. These
      liposomes fused to each other rapidly when the medium pH was lowered from 7 to 4.
      The polymerized liposomes were characterized in terms of particle size
      distribution. The liposome size increased approximately 20-fold from 110.0 +/-
      19.3 nm to 2046.7 +/- 487.4 nm as the pH was lowered. Cross-linking of the
      diacetylene lipids prevents drug leakage and the encapsulated drug can be
      instantaneously released at acidic pH condition. The ampicillin was nearly
      completely released (74.4 +/- 3.9%) from liposomes within 4 h under acidic pH
      conditions and the released amounts of ampicillin were analyzed by HPLC. Finally,
      the therapeutic effect was observed by the appearance of plaques on a lawn of E.
      coli, and fluorescent images of the PDA liposomes were taken from the plaques for
      drug release monitoring. As a result, this research demonstrates that such novel
      pH-sensitive polymerized liposomes have great prospects as a drug carrier.

PMID- 23862411
TI  - Colorimetric detection of DNA sequences using an organic solvent to induce the
      aggregation of label-free gold nanoparticles.
AB  - A novel assay based on a solvent for inducing the aggregation of AuNPs colloid
      was proposed to discriminate ssDNA from dsDNA. Eleven organic solvents with
      different polarity were investigated, and it was found that DMSO was possible to
      aggregate AuNPs at the amount of only 0.4 microL in a 50-microL detection system.
      Further research showed that 0.8 microL of DMSO could discriminate the ssDNA from
      dsDNA. Colorimetric detection with various conditions, including the ratio of the
      target to the probe, and the concentration of AuNPs and DNA, was investigated.
      The proposed method was successfully used for SNP typing, and unambiguous
      discrimination of a wild type from a mutant was obtained for the templates with
      the mismatched base at the 5'-end or in the middle of the target sequence. As no
      requirement of gold modification and detection instrument, we believe that this
      method will be much low in the cost for DNA detection.

PMID- 23862410
TI  - Evaluation of sustained drug delivery for bone morphogenetic protein on the
      functionalized nanotubular surface.
AB  - An effective loading method of the recombinant human Bone Morphogenetic Protein-2
      (rhBMP-2) on the implant surface is essential for promoting bone formation.
      However, the studies comparing the effectiveness of loading methods for rhBMP-2
      are insufficient. The objective of this study was to investigate the sustained
      rhBMP-2 delivery on the functionalized nanotubular surface. rhBMP-2 loading
      method on functionalized nanotubular surface was divided into 3 groups; coating
      and dry method, vacuum method, lyophilization method. A total of 10 ug rhBMP-2
      was loaded into functionalized nanotubular titanium implant surfaces (3.75 mm in
      diameter and 7 mm in length). The releasing time of rhBMP-2 was evaluated at 1,
      5, 7 days. The data were statistically analyzed with one-way ANOVA and a Post Hoc
      Bonferroni test. A sustained release pattern was observed in each groups and the
      amount of rhBMP-2 loaded was the highest in the lyophilization group. The results
      suggest that lyophilization method is effective method to load rhBMP-2 on the
      functionalized nanotubular surface and the functionalized nanotubular surface
      could be a sustainable useful carrier of rhBMP-2.

PMID- 23862412
TI  - Serotype-specific identification of Dengue virus by silicon nanowire array
      biosensor.
AB  - In this work, we demonstrated a silicon nanowire (SiNW) biosensing platform
      capable of simultaneously identifying different Dengue serotypes on a single
      sensing chip. Four peptide nucleic acids (PNAs), specific to each Dengue
      serotypes (DENV-1 to DENV-4), were spotted on different areas of the SiNW array
      surface, and the covalently immobilized PNA probes were then interacted with
      different Dengue serotypes target to establish the specificity of detection.
      Detection scheme is based on the changes in resistances due to accumulation of
      negative charges contributed by the hybridized DNA target. The results show that
      resistance changes only occur in regions where the Dengue target hybridizes with
      its complementary probe. What is more, a mixture of two different Dengue
      serotypes obtained from a one-step duplex RT-PCR was applied to the multiplex
      SiNW surface to validate SiNW capability to identify multiple Dengue serotypes on
      a single sensing platform. Through this study, we have established the multiplex
      SiNW biosensor as a promising device to detect multiple Dengue infections with
      high specificity.

PMID- 23862413
TI  - Electrospun collagen/poly(L-lactic acid-co-epsilon-caprolactone) hybrid
      nanofibrous membranes combining with sandwich construction model for cartilage
      tissue engineering.
AB  - Electrospinning has recently received much attention, showing great potential as
      a novel scaffold fabrication method for cartilage tissue engineering. In this
      study, we developed a biodegradable hybrid nanofibrous membrane of collagen and
      poly(L-lactic acid-co-epsilon-caprolactone) (PLCL, 75:25) by electrospinning for
      cartilage tissue engineering. The structure and cell affinity of collagen/PLCL
      membranes were analyzed by scanning electron microscopy (SEM) and microscopy. The
      sandwiched cell-scaffold constructs were kept in culture for 1 week in vitro and
      then implanted subcutaneously into nude mice for 4, 8 and 12 weeks. Gross
      observation, histological and immunohistological evaluation, glycosaminoglycan
      (GAG) analysis and Young's modulus measurements were performed at each post
      implantation time-point. Electrospun collagen/PLCL nanofibrous membranes could
      mimic the natural ECM and have good cell affinity. All the cell-scaffold
      constructs showed cartilage-like morphology with a white, smooth and glistening
      appearance after 4, 8 and 12 weeks of implantation. The abundance of GAG
      containing cartilaginous matrix appeared to increase greatly with implantation
      time. Furthermore, well-distributed cartilage and nearly no empty areas were
      observed in constructs even at 12 weeks post-implantation. In addition, the
      mechanical properties of the engineered cartilage after 12 weeks of implantation
      could reach 83% of that of native rabbit auricular cartilage. These results
      indicate that collagen/PLCL nanofibrous membranes with the sandwich construction
      model may serve as a new approach for cartilage tissue engineering.

PMID- 23862414
TI  - Bioinspired inimitable cadmium telluride quantum dots for bioimaging purposes.
AB  - Synthesis of quantum nanoparticles of specific size, shape and composition are an
      aspect important in nanotechnology research. Although these nanostructures are
      routinely synthesized by chemical routes, the use of microorganisms has emerged
      as a promising option. The synthesis of cadmium telluride (CdTe) quantum dots by
      two hitherto unreported marine bacteria (Bacillus pumilus and Serratia
      marcescens) is reported here. Ultraviolet-visible (UV-vis) spectroscopy indicated
      the synthesis of CdTe nanoparticles and X-ray diffraction (XRD) patterns
      implicated their crystalline face-centered cubic nature. The size of the
      synthesized CdTe nanostructures estimated by XRD and dynamic light scattering
      (DLS) analysis was found to be approximately 10 nm. Photoluminescence (PL)
      studies were used to confirm the fluorescence properties of these semi-conducting
      nanoparticles. Scanning electron microscope (SEM) analysis showed the presence of
      well-defined nanostructures and energy dispersive spectra (EDS) confirmed the
      microbial synthesis of these nanoparticles. These bio-inspired CdTe
      nanostructures could be effectively used in imaging of yeast and animal cells.
      This work thus describes a cost-effective green method for synthesizing highly
      fluorescent biocompatible CdTe nanoparticles suitable for bio-labeling purposes.

PMID- 23862415
TI  - Synthesis of cross-linked chitosan-based nanohydrogels in inverse miniemulsion.
AB  - Cross-linked chitosan (CS) nanohydrogels were successfully prepared via cross
      linking CS nanodroplets in inverse miniemulsions. The cross-linker was
      transferred to the CS nanodroplets via the evaporation from its aqueous solution
      and diffusion through the continuous phase. The formation of cross-linked CS
      nanohydrogels was confirmed by the morphological investigation during the
      reaction and the successful preparation of acidic aqueous dispersion of CS
      nanohydrogels. The size and size distribution of the CS nanodroplets and
      nanohydrogels were characterized by dynamic light scattering (DLS). The particle
      morphology of CS nanohydrogels was observed by transmission electron microscopy
      (TEM). The influence of the synthetic parameters on the particle properties and
      colloidal stability was investigated with respect to sonication time, surfactant
      type and amount, type of low polarity solvent, and concentration of CS solution.
      The cross-linked CS nanohydrogels could be easily re-dispersed in water, and
      showed a pH sensitivity.

PMID- 23862416
TI  - Sub-micronic capsules based on gelatin and poly(maleic anhydride-alt-vinyl
      acetate) obtained by interfacial condensation with potential biomedical
      applications.
AB  - New sub-micronic capsules based on a copolymer of maleic anhydride-alt-vinyl
      acetate and a natural polymer (gelatin) using an interfacial condensation method
      were obtained. Sub-micronic capsules were characterized by Fourier Transform
      infrared spectroscopy (FTIR), dynamic light scattering (DLS) method, zeta
      potential, scanning electron microscopy (SEM) and atomic force microscopy (AFM).
      The thermal properties were investigated by thermogravimetric analysis (TGA).
      According to some parameters of the synthesis reaction (polymer weight ratio,
      acetone/water ratio, surfactant concentration), the mean diameter of the sub
      micronic capsules can be tuned from 200 to 760 nm. The sub-micronic capsules show
      a higher agglomeration tendency as the amount of gelatin in their composition
      increases. The swelling capacity in aqueous solutions is dependent on the
      composition and size of the sub-micronic capsules, decreasing with their diameter
      and gelatin composition. The drug loading and release capacity was studied using
      Penicillin G (sodium salt) (PG), and it has been proved that it is influenced by
      the sub-micronic capsules morphology induced by preparation parameters.
      Encapsulation and controlled release of small molecule were successfully carried
      out, demonstrating the potential biomedical applications of these new easily
      obtained sub-micronic capsules.

PMID- 23862417
TI  - Enhancement effect of cytotoxicity response of silver nanoparticles combined with
      thermotherapy on C6 rat glioma cells.
AB  - The present studies reveal that silver nanoparticles (AgNPs) can induce apoptosis
      and enhance radio-sensitivity on cancer cells. In this paper, we mainly
      investigated the effect of AgNPs on rat glioma C6 cells upon the combination
      treatment of hyperthermia treatment (HTT). AgNPs were synthesized by a polyol
      process and the mean size was 15 nm. The particles showed dose-dependent
      cytotoxicity on C6 cells from the experimental data. Besides, we found that
      heating cells could enhance the contents of cell uptake of AgNPs. From the
      survival curves, AgNPs showed the ability to enhance thermo-sensitivity on C6
      cells. Our results revealed that AgNPs could have a potential application in
      enhancing effect on HTT induced killing of glioma cells.

PMID- 23862418
TI  - Electrospinning of ibuprofen-loaded composite nanofibers for improving the
      performances of transdermal patches.
AB  - The main aim of the present study was to electrospin ibuprofen (IBU)-loaded
      composite nanofibers to improve the performances of transdermal patches.
      Cellulose acetate/poly(vinyl pyrrolidone) (CA/PVP) blends were used to fabricate
      uniform nanofibers. Investigations on the physicochemical properties of CA/PVP
      solutions indicated that the addition of appropriate PVP improved the
      electrospinnability of original CA solutions. Detections on the physical states
      of IBU in medicated CA/PVP nanofibers suggested that IBU was uniformly
      distributed in nanofibers in an amorphous state. Comparing to IBU-loaded casting
      membrane, the medicated CA/PVP nanofibers provided a faster IBU diffusion manner
      and a better ex vitro skin permeation profile due to their high superficial areas
      and the amorphous IBU. Furthermore, CA/PVP nanofibers exhibited a high water
      vapor permeability, which could render an improved breathability to transdermal
      patches. In sum, the electrospun drug-loaded CA/PVP nanofibers exhibited great
      potentials to improve the thermodynamic stability and breathability of
      transdermal patches, which could be used to develop new types of transdermal drug
      delivery system (TDDS).

PMID- 23862419
TI  - Titanium dioxide nanotube modified implants: an animal study on bone formation.
AB  - This study examined the bone response to titanium dioxide nanotube modified
      implants. A total of 24 implants were placed in the femur of 4 beagles. Before
      placement, screw-shaped implants were classified into 3 groups; machined surface
      (group M), titanium dioxide nanotube modification of the machined surface (group
      MN) and titanium dioxide nanotube modification of the RBM surface (group RN). The
      texture morphology was observed via scanning electron microscopy. Animals were
      euthanized after 4 and 12 weeks of submerged healing and the histologic and
      histomorphometric analyses were performed. Groups MN and RN showed a
      significantly higher percentage of mineralized bone than that in group M (p <
      0.05). The results of this in vivo study constitute significant evidence that the
      presence of the titanium dioxide nanotubes enhance osseointegration of implants.

PMID- 23862420
TI  - Antitumor efficacy of paclitaxel-loaded polylactide/ poly(ethylene glycol)
      nanoparticles combination with exercise in tumor-bearing mice.
AB  - The nanoparticles (NPs) provide a promising prospect for tumor therapy, and
      exercise is also becoming readily and accepted as a beneficial adjunct therapy to
      maintain or enhance quality of life in cancer patients. We investigate the
      antitumor efficacy of paclitaxel (PT) loaded polylactide/poly(ethylene glycol)
      NPs (PT-PLA/PEG NPs) under the exercise conditions. Results showed that within
      the first 7 days, the PT concentration in tumor maintained at a higher level in
      the PT-PLA/PEG NPs + exercise (PT-PLA/PEG NPs + EX) group as compared with the PT
      PLA/PEG NPs group. All the phagocytosis rates of macrophages were significantly
      decreased below the CON in exercise group. The most significant antitumor effect
      was observed in PT-PLA/PEG NPs + EX group, demonstrating that the PT-PLA/PEG NPs
      improved the concentration of PT, and exercise could further increased its
      therapeutic efficiency for tumor. These researches may provide an effective means
      for tumor therapy.

PMID- 23862422
TI  - Phototoxicity of zinc oxide nanoparticles in HaCaT keratinocytes-generation of
      oxidative DNA damage during UVA and visible light irradiation.
AB  - Zinc oxide nanoparticles (nano-ZnO) are one of the most commonly used
      nanomaterials in industrial products including paints, cosmetics, and medical
      materials. Since ZnO is a well-known photocatalyst, it is important to further
      study if nano-ZnO cause phototoxic effect on skin cells under UVA-irradiation and
      visible light illumination. Human-derived keratinocytes (HaCaT) were treated with
      1-20 microg/mL of nano-ZnO (< 50 nm) and then exposed to UVA (0.5-2 J/cm2).
      Twenty four hours later, cell viability, membrane integrity, and oxidative DNA
      damage were determined by MTS assay, lactate dehydrogenase (LDH) release, and the
      formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct, respectively. High
      concentration of nano-ZnO (10-20 microg/mL) significantly induced cytotoxicity,
      whereas 0.5-2 J/cm2 of UVA irradiation dose-dependently aggravated nano-ZnO
      induced cell death via induction of LDH release and DNA damage. The level of
      photocytotoxicity is mainly dependent on the level of reactive oxygen species
      (ROS) production. UVA irradiation of nano-ZnO in methanol induced lipid
      peroxidation in a light dose and substrate dose response manner. Electron spin
      resonance (ESR) spin trapping studies confirmed that both hydroxyl radical and
      superoxide anion radical were formed during photoirradiation, while nano-ZnO
      induced hydroxyl radical formation is not evolved from superoxide. In addition,
      nano-ZnO dose-dependently induced single strand DNA break in supercoiled phi x
      174 plasmid DNA. Under visible light illumination, nano-ZnO induced the LDH
      leakage, hydroxyl radical generation, and 8-OHdG formation in a dose-dependent
      manner. Collectively, these results suggest the photocytotoxic and photogenotoxic
      effects of nano-ZnO on human skin keratinocytes.

PMID- 23862421
TI  - Effect of anatase TiO2 nanoparticles on the growth of RSC-364 rat synovial cell.
AB  - Nanoscale materials (such as TiO2, hydroxyapatite nanoparticles) have gained much
      concern in the coating of implants for cell adhesion and growth to improve the
      osteoconductivity. However, due to attrition and corrosion, the wear particles
      would be generated from the joint in living organism, and influence the
      physiological function of synovial membranes in joint cavity. In this study, the
      potential cytotoxicity of anatase TiO2 nanoparticles (TiO2 NPs) on rat synovial
      cell line 364 (RSC-364) was investigated. After treatment with different
      concentrations of TiO2 NPs (0, 3, 30, 300 microg/ml), the viability of RSC-364
      cells were decreased in a dose-dependent manner. TiO2 NPs exposure could disrupt
      the integrity of cell plasma membrane, leading to the increased leakage of
      lactate dehydrogenase (LDH) into the culture medium. TiO2 NPs were uptaken by RSC
      364 cells. The ultrastructure of RSC-364 cells was changed such as nuclear
      shrinkage and mitochondrial swelling. The reactive oxygen species (ROS) was over
      produced especially in the cells exposed to 30 and 300 microg/ml TiO2 NPs. The
      activities of endogeneous antioxidant enzymes, superoxide dismutase (SOD) and
      catalase (CAT), were significantly decreased. The increased lipid peroxidation
      product (malondialdehyde, MDA) suggests the oxidative damage in cells. The flow
      cytometry detected that the cell cycle was blocked in G0/G1 phase, inhibiting the
      cell proliferation. These preliminary results indicate the oxidative stress
      injury and cytotoxicity of anatase TiO2 NPs on rat synovial cells. The reasonable
      and safe application of nanomaterials in artificial implants needs further study.

PMID- 23862423
TI  - Temperature and magnetic field effects on electron transport through DNA
      molecules in a two-dimensional four-channel system.
AB  - We utilize a two-dimensional four-channel DNA model, with a tight-binding (TB)
      Hamiltonian, and investigate the temperature and the magnetic field dependence of
      the transport behavior of a short DNA molecule. Random variation of the hopping
      integrals due to the thermal structural disorder, which partially destroy phase
      coherence of electrons and reduce quantum interference, leads to a reduction of
      the localization length and causes suppressed overall transmission. We also
      incorporate a variation of magnetic field flux density into the hopping integrals
      as a phase factor and observe Aharonov-Bohm (AB) oscillations in the
      transmission. It is shown that for non-zero magnetic flux, the transmission zero
      leaves the real-energy axis and moves up into the complex-energy plane. We also
      point out that the hydrogen bonds between the base pair with flux variations play
      a role to determine the periodicity of AB oscillations in the transmission.

PMID- 23862424
TI  - Microbial synthesis of silver nanoparticles.
AB  - The objectives of this research were to study biogenic synthesis of Ag(0)
      nanoparticles and to determine the effects of various experimental conditions
      such as silver nitrate concentrations, pHs and temperatures controlling for the
      optimal biosynthesis of Ag(0) nanoparticles. The metal-reducing bacteria formed 5
      15 nm-sized Ag(0) nanoparticles by reduction of 0.5-1 mM silver nitrate under the
      conditions around 15-25 degrees C and medium pH 7.5-8.5 within 3 days of
      incubation. These results not only show that the bacteria enzymatically reduced
      Ag(I), but also offer methods for microbial synthesis of homogeneous silver
      nanoparticles and silver recovery from the natural environments.

PMID- 23862425
TI  - Tailoring the band gap and transport properties of Cu3BiS3 nanopowders for
      photodetector applications.
AB  - We report a facile route to synthesize high quality earth abundant absorber
      Cu3BiS3, tailoring the band gap with the morphology manipulation and thereby
      analyzed the secondary phases and their role in the transport property. The
      sample at 48 hours reaction profile showed good semiconducting behavior, whereas
      other samples showed mostly a metallic behavior. Band gap was varied from 1.86 eV
      to 1.42 eV upon controling the reaction profile from 8 hours to 48 hours. The
      activation energy was calculated to be 0.102 eV. The temperature coefficient of
      resistance (TCR) was found to be 0.03432 K(-1) at 185 K. The IR photodectection
      properties in terms of photoresponse have been demonstrated. The high internal
      gain (G = 3.7 x 10(4)), responsivity (R = 3.2 x 10(4) A W(-1)) for 50 mW cm(-2)
      at 5 V make Cu3BiS3, an alternative potential absorber in meliorating the
      technological applications as near IR photodetectors.

PMID- 23862426
TI  - Synthesis and optoelectronic properties of nanocomposites comprising of poly(9,9
      dioctylfluorene)-block-poly(3-hexylthiophene) block copolymer and graphene
      nanosheets.
AB  - A novel conjugated block copolymer, poly(9,9-dioctylfluorene)-block-poly(3
      hexylthiophene) (PFBPT) and its nanocomposite containing graphene sheets were
      synthesized for enhancing optoelectronic performance. Graphene sheets were in
      situ formed in the polymer matrix via a reduction of octadecylamine
      functionalized graphite oxide, where the graphite oxide came from acidification
      and exfoliation of graphite. The blue-green light-emitting poly(9,9
      dioctylfluorene) block and red-orange light-emitting poly(3-hexylthiophene) block
      exhibit a combined white electroluminescence when the composite materials were
      fabricated as the emitting layer of a polymeric light-emitting diode (PLED).
      Graphene does not alter the optical characteristics wavelength of PFBPT but
      electric conductivity increases with the amount of graphene. The HOMO and LUMO
      were measured and the band gap is smaller with existence of graphene. The
      threshold voltage decreases with an increase in the graphene content. The device
      fabricated with PFBPT/graphene nanocomposite containing 1% graphene has a maximum
      white-light luminescence at a voltage of 9.0 V.

PMID- 23862427
TI  - Preparation of the poly(arylene sulfide sulfone)/multi-walled carbon nanotubes
      composites via in situ polymerization.
AB  - The nanocomposites of Multiwall carbon nanotubes (MWNTs) and poly(arylene sulfide
      sulfone) (PASS) were prepared via in situ polymerization. The compounds were
      found to distribute uniformly and had excellent thermal properties with glass
      transition temperatures (T(g)) of 222-224 degrees C and initial degradation
      temperature (T(d)) of 437.7-445 degrees C. They had better solubility and could
      dissolve in strong aprotic solvents such as N-methyl-2-pyrrolidone (NMP),
      dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and so on. After acidification
      and fluobenzene-functionalization treatment, the MWNTs and polymer matrix via in
      situ polymerziation showed better compatibility than the composite mixing
      directly. Additionally, the composites prepared via in situ polymerization had
      good electrical conductivity of 10(14)-10(7.6) omega x m and mechanical
      properties with Young's modulus of 0.63-1.08 GPa.

PMID- 23862428
TI  - Synthesis and characterization of one-dimensional bifunctional carbon
      nanotubes/Fe3O4@SiO2 (FITC) nanohybrids.
AB  - A new type of one-dimensional bifunctional CNTs/Fe3O4 @ SiO2 (FITC) nanohybrids
      with both magnetic and fluorescent properties were fabricated by a polyol method
      combined with stober method. The CNTs/Fe3O4 @ SiO2 (FITC) nanohybrids exhibit
      strong and stable photoluminescence emission at about 520 nm, display
      superparamagenetic behavior with high saturation magnetization and possess MRI
      function at room temperature. All these properties make the CNTs/Fe3O4 @ SiO2
      (FITC) nanohybrids a potential candidate for biomedical agent such as MRI
      contrast agent, cells labelling, in-vivo image and drug deliver for cancer
      diagnosis and treatment.

PMID- 23862429
TI  - Enhancement of conductive pathway of functionalized CNT dispersed
      poly(methylmethacrylate) nanocomposites.
AB  - Poly(methylmethacrylate) (PMMA) beads were coated with pristine multi-walled
      carbon nanotube (MWNT) using various mixing medium and then nanocomposite were
      fabricated. Results were compared with acid functionalized MWNT (f-MWNT) coated
      PMMA bead nanocomposites. In addition, a combination of different mixing medium
      was also used to compare and to optimize the homogeneously dispersed MWNT and f
      MWNT coating on PMMA beads. A homogeneous coating of nanotubes on the PMMA beads
      were observed in a DMF solution and confirmed by optical microscopy, SEM, Raman
      mapping, and sheet resistance measurements. Moreover, percolation and electrical
      properties were also compared with respect to nanotubes dispersion in the PMMA
      resin matrix. Nanocomposites prepared by coating PMMA beads with pristine CNT
      exhibited improvement of electro conductive pathway i.e., lowering percolation
      threshold below 0.1 wt% of MWNT content. The result was also compared with acid
      treated MWNT coated PMMA beads and acid treated dispersed MWNT in PMMA resins.
      The ultra-low electrical surface resistance of nanocomposites using trace amounts
      of MWNT coating on PMMA beads has not been reported so far.

PMID- 23862430
TI  - Nanocomposite formation in haematite-Mg, Ti system induced by high-energy ball
      milling.
AB  - Reactant materials of haematite and Mg, Ti powders have been milled, where pure
      metals are used as reducing agent. It is found that nanocomposite powders in
      which MgO and TiO2 are dispersed in alpha-Fe matrix with nano-sized grains are
      obtained by MA of Fe2O3 with Mg and Ti for 30 min and 5 hours, respectively. It
      is suggested that the shorter MA time for the nanocomposite formation in Fe2O3-Mg
      is due to a larger negative heat associated with the chemical reduction of
      reactant materials. X-ray diffraction results show that the average grain size of
      alpha-Fe in alpha-Fe/TiO2 nanocomposite powders is in the range of 40 nm. From
      magnetic measurement, we can also obtain indirect information about the details
      of the solid-state reduction process during MA.

PMID- 23862431
TI  - The effect of optical properties on photovoltaic performance in dye-sensitized
      TiO2 nanocrystalline solar cells.
AB  - In this study, well-crystallized TiO2 nanoparticles with average size of -20 nm
      were synthesized by hydrolysis of titania salt in aqueous medium. The effect of
      the optical properties of the obtained titania particles based thin films with
      different thickness on the photovoltaic performance of dye-sensitized solar cells
      were investigated. Differential thermal analysis/thermo-gravimetric analysis,
      scanning electron microscopy, transmission electron microscopy and X-ray
      diffraction were used to characterize the morphology, structure and crystal
      formation of the obtained samples. The optical properties such as reflectance and
      transmittance of the photoanodes with different thickness were systematically
      investigated. The reflectance property increased with increasing the film
      thickness, however, the transmittance property showed the opposite way. The
      improved scattering property with increasing the film thickness facilitated
      efficient utilization of solar spectrum, which was verified by incident photon-to
      current conversion efficiency. The maximum energy conversion efficiency of 5.0%
      was achieved on photoelectrode film with 17.8 microm.

PMID- 23862432
TI  - Solid-state combinatorial chemistry of Eu(2+)-doped Sr-Al-Si-O-N phosphors.
AB  - Sr-Al-Si-O-N composition space was screened by a solid state combinatorial
      chemistry. For this sake, powder mixtures of Sr3N2, alpha-Si3N4, AIN and Eu3N2
      was fired at 1500 degrees C-1900 degrees C for 2 h under 1.0 Mpa N2 using a gas
      pressurized sintering (GPS) furnace. The resultant phosphors were phase
      identified, and the photo luminescence was examined. The Sr-Al-Si-O-N phosphors
      are blue-Green and orange in color and emit in the region of 520-630 nm depending
      on synthesized temperature. Considering an intense excitation band in blue LED
      and emission band, these materials can be used as novel conversion phosphor for
      White-LEDs, if the luminance was improved.

PMID- 23862433
TI  - Preparation and optical properties of YH2:Er2+ and Y2O3:Er3+ nanoparticles.
AB  - The rare earth hydride nanoparticles have been prepared successfully by a novel
      method of hydrogen plasma-metal reaction. The YH2:Er2+ nanoparticles of 40-50 nm
      were polycrystalline and in hexagonal shape. The Y2O3:Er3+ nanoparticles were
      fabricated by annealing the hydride nanoparticles in air at 300, 500 and 700
      degrees C, respectively. The influence of the sintering temperature on the size,
      crystal structure and optical properties of these nanoparticle samples were
      investigated. After annealing, the Y2O3:Er3+ nanoparticles became single
      crystalline and spherical shape, and the mean particle size of these particles
      did not change apparently upon the annealing temperature up to 700 degrees C.
      With the increase of the annealing temperature, the absorption intensity of YH2
      in the Fourier transform infrared spectroscopy spectra decreased and the peak
      position moved to high-frequency, whereas the absorption intensity of Y2O3 was
      enhanced. The intensity of the near-IR fluorescence spectra of the Y2O3:Er3+
      nanoparticles increased remarkably with the increase of the annealing temperature
      from 300 to 700 degrees C. The Y2O3:Er3+ sample sintered at 700 degrees C
      exhibited a strong photoluminescent intensity at the wavelength of about 1535 nm,
      with a narrow full width of 6 nm at the half maximum. This makes the Y2O3:Er3+
      nanoparticles promising for the applications in the optical communication
      devices.

PMID- 23862434
TI  - Method for fabricating micro/nanostructures via scanning probe microscope and
      anisotropic wet etching.
AB  - The direct modification of silicon, other semiconductors and metal surfaces by
      the process of local anodic oxidation via electric field from scanning probe
      microscope (SPM) in conjunction with the absorbed water in atmosphere as the
      electrolyte is a promising method for fabricating micro/nanostructures. We
      demonstrated that the process of SPM oxidation and anisotropic wet chemical
      etching is a low cost and reliable method to produce smooth and uniform etched
      structures on silicon substrates. Using silicon oxide nanopatterns produced on H
      passivated (110) Si surfaces as etching masks, and due to the large (110)/(111)
      anisotropic ratio of etching rate and the large Si/SiO2 etching selectivity at a
      relatively low etching temperature and an optimal concentration of aqueous KOH
      etchant, high-aspect-ratio grating structures have been fabricated by anisotropic
      wet etching. The approach of combining scanning probe lithography (SPL) with
      etching technique provides an alternative lithography route to fabricate
      functional nanophotonic or nanoelectronic devices.

PMID- 23862435
TI  - Photocatalytic degradation of dyestuff wastewater with Zn(2+)-TiO2-SiO2
      nanocomposite.
AB  - A novel photocatalyst of Zn(2+)-TiO2-SiO2 nanocomposite has been prepared by a
      sol-gel method, which is used for the degradation of Rhodamine B (RhB) and Congo
      red (CR) as the probe dyestuff that are notorious organic compounds present in
      dyes wastewater. The prepared samples are characterized by low temperature N2
      adsorption (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), UV
      vis diffuse reflectance spectroscopy (DRS) and Fourier transformed infrared
      spectroscopy (FT-IR). It is found that the nanocomposite of Zn(2+)-TiO2-SiO2
      exhibits much higher photocatalytic activity under both UV light and visible
      light irradiation as compared with Degussa P25, Zn(2+)-TiO2 and SiO2-TiO2. The
      photodegradation efficiencies of RhB (5 mg/L) and CR (10 mg/L) can reach above
      90% and 83% for 1.5 h visible light irradiation, respectively. Synergetic effect
      between Zn(2+)-SiO2-doping not only inhibit the crystal growth and anatase-to
      rutile transformation of TiO2 nanocatalyst, but also extend the light response to
      the visible region, which provides a good way and material in the degradation
      field of dyes wastewater.

PMID- 23862436
TI  - Fabrication and electrical properties of low temperature-processed thin-film
      transistors with chemical-bath deposited ZnO layer.
AB  - ZnO film was grown on ZnO quantum dot seed layer-coated substrate by a low
      temperature chemical bath deposition, where sodium citrate serves as a complexing
      agent for Zn2+ ion. The ZnO film deposited under the optimal condition exhibited
      a highly uniform surface morphology with a thickness of approimately 30 nm. For
      the fabrication of thin-film-transistor with a bottom-gate structure, ZnO film
      was chemically deposited on the transparent substrate of a seed layer-coated
      SiN(x)/ITO (indium tin oxide)/glass. As-deposited ZnO channel was baked at low
      temperatures of 60-200 degrees C to investigate the effect of baking temperature
      on electrical performances. Compared to the device with 60 degrees C-baked ZnO
      channel, the TFT performances of one with 200 degrees C-baked channel were
      substantially improved, exhibiting an on-off current ratio of 3.6 x 10(6) and a
      saturated field-effect mobility of 0.27 cm2/V x s.

PMID- 23862437
TI  - Wetting and surface energy of vertically aligned silicon nanowires.
AB  - The vertically aligned silicon nanowires (SiNWs) have been synthesized by metal
      assisted chemical etching process on commercially available p type silicon wafer.
      The aspect ratios of the SiNWs have been modified by simply varying the etching
      time. The microstructures of the as prepared samples have been investigated with
      the field emission scanning electron microscope as well as with a high resolution
      transmission electron microscope. The bonding information has been obtained by
      Fourier transformed infrared spectroscopy and X-ray photoelectron spectroscopy.
      The contact angles for water with the as-prepared SiNWs films were measured and
      found to be highly dependent upon the aspect ratio of the as synthesized wires.
      For obtaining a deep insight regarding the reasons behind this dependence the
      surface energies of the as prepared SiNWs films have been calculated by Owens
      method using two liquids, water and glycerol. The porosity of the films has been
      calculated indirectly from the equilibrium equations. It has been found that the
      etching time has a profound effect on the aspect ratio and thus on the surface
      energy of SiNWs that governs the wetting behaviour of the as prepared samples.

PMID- 23862438
TI  - Simulation study on gold nanoparticle-cellular membrane complex in endocytosis
      process.
AB  - Gold nanoparticles (AuNPs) are of biomedical importance, such as delivery
      vectors. Therefore, we used all-atom molecular dynamic simulations to study the
      interaction of AuNPs with cell membrane (DMPC bilayer). We observed that the
      AuNPs adhered spontaneously on the surface of the cellular membrane from the bulk
      phase, largely as a result of the AuNP-DMPC headgroup attraction. We calculated
      the potential of mean force for transferring an AuNP through a DMPC bilayer. It
      was observed that a high energetic barrier to AuNP was inserted into the
      hydrophobic core of the bilayer. The inclusion of AuNP induced local bilayer
      deformation and slowed fluidity of the lipid molecules in the vicinity of it. As
      the size of the AuNP increased, the lipids in the vicinity of the AuNP had larger
      local deformation and slower fluidity. We found that a nanoparticle-membrane
      complex was formed by the AuNP and its neighbor lipids. These neighbor lipids
      moved laterally together with AuNP. On average, they moved significantly more
      slowly than the other lipids. The nanoparticle-membrane complex not only provided
      a clue for endocytosis mechanism regulating the translocation of AuNPs across the
      cellular membrane but also helped us to better understand the endocytosis
      process.

PMID- 23862439
TI  - A closed-tube detection of loop-mediated isothermal amplification (LAMP) products
      using a wax-sealed fluorescent intercalator.
AB  - LAMP is an isothermal amplification method that can achieve ultra-high
      sensitivity and specificity. However, the conventional detection of LAMP
      amplicons can lead to cross-contamination due to the need to open the reaction
      tube which contains a large number of amplicons. To achieve closed-tube LAMP
      detection, we have developed a method that separates a solution of SYBR Green I
      (SGI) from the LAMP reagents using temperature-sensitive wax. The SGI is sealed
      in the bottom of the tube so not to interfere with the LAMP reaction, but is
      released into the mixture after the completion of the reaction by melting the
      wax. To enable the analysis of the closed-tube LAMP samples automatically, an
      instrument based on this new method was constructed. The background measurement
      of the LAMP due to primer dimers was significantly reduced by detecting the
      amplicons at 75 degrees C. HBV and 2009 H1N1 virus were successfully analyzed by
      the LAMP assay using tubes containing wax-sealed SGI and the prototype
      instrument, indicating that the method has the advantage of easy set-up (no extra
      components need to be added into the LAMP mixture for detection), high
      sensitivity (fluorescent intercalator), low background (detected at 75 degrees C)
      and no cross-contamination (closed-tube). Therefore, the novel LAMP detection,
      coupled with the instrument has the potential to be a diagnostic tool for a
      number of clinical applications in hospitals as well as on-site screening of
      pathogenic agents.

PMID- 23862440
TI  - Concentration enhanced upconversion luminescence in ZrO2:Ho3+, Yb3+
      nanophosphors.
AB  - The upconversion luminescence properties of ZrO2:Ho3+ and co-doped ZrO2:Ho3+,
      Yb3+ nanophosphors with various concentrations of Yb3+ ions were synthesized via
      a solvothermal reaction method. Our samples have a nearby spherical shape and an
      average crystal size was about 80 nm. For low concentrations of Yb3+ ion, the
      crystalline structure changed from tetragonal to monoclinic phase as the Yb3+
      concentration increased to 3 mol% Yb3+ ions. As the Yb3+ concentration increased
      to above 5 mol%, ZrO2 nanophosphors displayed a very stable tetragonal phase. The
      sample shows a strong green (550 nm) and weak red (660 nm) and near infrared (757
      nm) upconversion emission corresponding to the transitions of Ho3+:5F4/5S2 -->
      5I8, 5F5 --> 5I8 and 5S2 --> 5I7, respectively. The energy transfer (ET)
      processes between the Ho3+ and Yb3+ ions and the involved mechanisms have been
      investigated. Experimental results suggest that two-photon upconversion processes
      are taking place under excitation by a 975 nm.

PMID- 23862441
TI  - Silicon nitride nanopores for nanoparticle sensing.
AB  - In recent years, nanopore has attracted broad attention as an essential technique
      for DNA sequencing and nanoparticle sensing. This work presented a fundamental
      study of nanoparticle translocation through silicon nitride nanopores. Since
      particles with rather high charge to mass ratio, such as DNA and proteins, have
      been widely studied, there was still little information about the translocation
      behavior of nanoparticles with low charge/mass ratio. However, these
      nanoparticles include viruses and colloids are important potential sample for
      nanopore sensing technique. In order to screen nanoparticles' size,
      concentration, surface property by apply silicon nitride nanopores, and fulfill
      specific recognition which could be applied in laboratory medicine and
      environmental monitoring, optimal experimental conditions needed to be confirmed.
      In this paper, polystyrene (PS) bead was used as an example to provide reference
      towards this condition. The effects of nanopore/nanoparticle diameter ratio and
      bias voltage on sensing results were analyzed in this work. We found that lower
      precision accuracy might be demonstrated by the larger pore (120 nm) while the
      translocation velocity tended to be slowed down. By increasing the bias voltage
      could favor the detection productiveness. In spite of the intense interest, the
      baseline fluctuations and vague event bounds aggravated are far from understood.

PMID- 23862442
TI  - Enhanced functional properties of ZrO2/SiO2 hybrid nanosol coated cotton fabrics.
AB  - In this present investigation, the colloidal silica and nano ZrO2 embedded silica
      solution were prepared using sol-gel method followed by the sonication process.
      The particle size was measured for the prepared silica sol with and without ZrO2
      nanoparticles. The prepared nanoparticles were coated on the cotton fabric
      through pad dry method. The phase and functional group analysis of the cotton
      fabrics after coating reveals the presence of metal oxides on the surface. The
      surface morphology of the coated fabrics analysed using SEM shows that the
      nanoparticles were in spherical morphology with slight agglomerations. The
      element analysis confirms the presence of silica (SiO2) and ZrO2/SiO2
      nanoparticles along with cellulose on the surface. The washing durability of the
      coated fabrics after 5th and 10th wash indicates that the nanoparticles were
      strongly adhered on the fabric surface. The burning performance of coated fabrics
      is in the order of ZrO2/SiO2 (19.5 s) > SiO2 (11.3 s) before and after wash; UV
      resistance of fabric was in the order of ZrO2/SiO2 > SiO2 > uncoated fabric.
      Cotton fabrics coated with ZrO2/SiO2 particles show better UV and flammability
      protection for textile applications.

PMID- 23862443
TI  - Structural properties, interface modes and magnetophonon resonances in the double
      quantum well structure.
AB  - The Double Quantum Well structure (DQWs) of special engineering providing a
      rectangular shape of QW's, is investigated. The Scanning Transmission Electron
      Microscopy (STEM) observations confirmed a high quality of interfaces and smooth
      change of the In-content in a rectangular shape QW. Micro-Raman experiment
      enabled to detect interface phonons in DQWs which are manifested in Magnetophonon
      Resonance. This contribution of interface phonons in the electron magneto
      transport is important because as could be expected, the role of these phonons
      will increase in case of electron transport in the Double Quantum Wires
      fabricated from DQWs investigated.

PMID- 23862444
TI  - Electrodepositing behaviors and properties of nano Fe-Ni-Cr/SiC composite
      coatings from trivalent chromium baths containing compound carboxylate-urea
      system.
AB  - The nano Fe-Ni-Cr/SiC composite coatings were prepared using pulse
      electrodeposition method from trivalent chromium baths containing compound
      carboxylate-urea system and nano SiC in ultrasonic field. The effects of the
      carboxylate-urea system on the nano Fe-Ni-Cr/SiC composite coatings have been
      investigated. These results indicated that the SiC and Cr contents and the
      thickness of the Fe-Ni-Cr/SiC composite coatings could be obviously improved by
      the compound carboxylate-urea system. The steady-state polarization curves showed
      that the hydrogen evolution reaction (HER) could be significantly inhibited by
      the compound carboxylate-urea system, which was benefit to increase the SiC and
      Cr contents and the thickness of the composite coatings. The cyclic voltammetry
      (CV) curves showed that the cathodic polarization of the matrix metal ions could
      be increased in the bath containing the compound carboxylate-urea system. Thus, a
      compact Fe-Ni-Cr/SiC composite coating could be obtained using this technique.
      The surface morphology of the Fe-Ni-Cr/SiC composite coatings checked with the
      scanning electron micrographs (SEM) showed that the surface smoothness could be
      also improved and the microcracks and pinholes could be decreased due to the
      presence of the compound carboxylate-urea system. The phase composition of the as
      posited coating was measured by the X-ray diffraction (XRD). XRD data showed that
      the as-posited coating was Fe-Ni-Cr/SiC composite coating. The chemical
      composition of the coating was investigated by energy dispersive spectrum (EDS)
      analysis. The result showed the functional Fe-Ni-Cr/SiC composite coatings with
      4.1 wt.% SiC and 25.1 wt.% Cr, and 23.9 microm thickness were obtained in this
      study, which had best corrosion resistance according to the results of the
      typical potentiodynamic polarization curves of the Fe-Ni-Cr/SiC composite
      coatings.

PMID- 23862445
TI  - Chemically synthesized graphene for electrochemical biosensing.
AB  - We report a new chemical method for synthesis of graphene with good yield.
      Graphene obtained by this chemical route was subjected to electrochemical
      characterization using two different redox materials for their suitability in
      electrochemical biosensing applications. The synthesized graphene was used for
      the detection of neurotransmitters like dopamine and serotonin. The electrodes
      exhibited 20% +/- 5% (N = 5) decrease in their signal after forty five days
      storage in the laboratory atmosphere. High stability of chemically synthesized
      graphene as electrochemical biosensor is presented in this work.

PMID- 23862446
TI  - A simple chemical vapor deposition method for the production of highly conductive
      polymer poly(3,4-ethylenedioxythiophene).
AB  - Conductive thin films of Poly(3,4-ethylenedioxythiophene) (PEDOT) have been
      successfully deposited on a variety of substrates by a simple chemical vapor
      deposition (CVD) method starting from the liquid monomer (EDOT) and using FeCl3
      as a catalyst. Resistivity measurements indicated very good conductivity of the
      material, comparable with other previously reported values for PEDOT deposited by
      CVD. Further cyclic voltammetry measurements indicated a value of around -4.7 eV
      for the HOMO level of PEDOT in the deposited films, in agreement with other
      reported values. This value is within the bandgap of most semiconductors, and
      together with the relative low internal resistance makes our material an ideal
      candidate as a solid-state hole transport material for dye sensitized solar
      cells.

PMID- 23862447
TI  - Semi-transparent a-IGZO thin-film transistors with polymeric gate dielectric.
AB  - We report the fabrication of semi-transparent a-IGZO-based thin-film transistors
      (TFTs) with crosslinked poly-4-vinylphenol (PVP) gate dielectric layers on PET
      substrate and thermally-evaporated Al/Ag/Al source and drain (S&D) electrodes,
      which showed a transmittance of 64% at a 500-nm wavelength and sheet resistance
      of 16.8 omega/square. The semi-transparent a-IGZO TFTs with a PVP layer exhibited
      decent saturation mobilities (maximum approximately 5.8 cm2Ns) and on/off current
      ratios of approximately 10(6).

PMID- 23862448
TI  - Magnesium-zinc ferrite nanoparticles: effect of copper doping on the structural,
      electrical and magnetic properties.
AB  - In this paper, Mg0.5Zn0.5-Cu(x)Fe2O4 ferrites nanoparticles were synthesized by
      facile co-precipitation route and characterized in detail in terms of their
      structural, electrical and magnetic properties as a function of Cu concentration.
      The prepared samples have cubic spinel phase as confirmed by X-ray diffraction
      patterns. The decrease of the lattice constant and increase of X-ray density
      indicate the solubility of Cu ions in the spinel lattice. The AC conductivity
      measurements between 300 K and 773 K at different frequencies 1 KHz up to 1 MHz,
      showed two different behaviors as semiconductor-like at high temperature and
      frequency depending behavior associated with dispersion phenomena at low
      temperatures. The conduction mechanism in the system is influenced by Cu
      concentration and the dominant one is the hopping conduction mechanism.
      Dielectric measurements at the same conditions of temperatures and frequencies
      exhibited that the dielectric loss increases with increasing the temperature and
      decreasing the frequency indicating the semiconducting nature of the ferrite
      compounds. An anomalous behavior of the dielectric loss is observed in samples
      with high Cu content which explained in terms of resonance between frequency
      accompanied the electronic hopping and the frequency of the external electric
      field. The analysis of Mossbauer spectra revealed that copper free compound is
      super-paramagnetically relaxed in nature and zinc free compound demonstrates
      ferrimagnetic order. Moreover, hyperfine field spectrum shows the migration of Cu
      ions from octahedral to tetrahedral site in zinc free compound.

PMID- 23862449
TI  - Optical and magnetic properties of zinc oxide quantum dots doped with cobalt and
      lanthanum.
AB  - Cobalt and Lanthanum-doped ZnO QDs are synthesized by a modified sol-gel method
      under atmospheric conditions. The as-prepared quantum dots are characterized by X
      ray powder diffraction (XRD), energy dispersive X-ray (EDX) analysis and high
      resolution transmission electron microscopy (HRTEM). The optical properties of
      the products are studied by fluorescent spectroscopy. With a proper Co and La
      doping, these nanoparticles possess exceptionally small size and enhanced
      fluorescence. Hysteresis loops of un-doped ZnO QDs and Co and La-doped ZnO QDs
      indicate that both the samples show ferromagnetic behavior at room temperature.
      Finally, these nanoparticles can label the BGC 803 cells successfully in short
      time and present no evidence of toxicity or adverse affect on cell growth even at
      the concentration up to 1 mM. We expect that the as-prepared Co and La-doped ZnO
      QDs can provide a better reliability of the collected data and find promising
      applications in biological, medical and other fields.

PMID- 23862450
TI  - Phase behavior and thermal stabilization study of blue phase liquid crystal
      unfunctionalized nanoparticle blends.
AB  - We have studied the phase behavior of blue phase liquid crystal (BPLC)
      unfunctionalized nanoparticle (NP) blends. Two different types of NPs which have
      different anchoring properties have been studied. Interestingly, Silica NP doped
      BPLC blends have revealed a small but clear positive shift of the Isotropic-BP
      phase transition temperature for lower concentration of NPs whereas with higher
      percentage of NPs we have observed a mixed phase consisted with chiral nematic
      (N*) and BP. On the other hand, low concentration polyhedral oligomeric
      silsesquioxanes (POSS) NPs which have stronger anchoring force than Silica NPs
      have enabled BP to stabilize thermally. Our experimental results agrees with the
      recent theory predicted that NP-defect interaction strongly depends on the
      interfacial energy between NP and LC which may be responsible for the observed
      effects in unfunctionalized NP-BPLC composite system.

PMID- 23862451
TI  - Energy transfer in Sr2MgSi2O7:Eu2+ phosphors in nano scale and their application
      to solid state lighting with excellent color rendering.
AB  - On the basis of structural information of its host material which shows excellent
      stability and absorption efficiency in ultra-violet (UV) region, a blue-emitting
      Sr2MgSi2O7:Eu2+ (SMS:Eu2+) phosphor was synthesized, and its photoluminescence
      (PL) performance was systematically optimized. In order to enhance its PL
      properties, Ce3+ was added as a sensitizer based on the energy transfer from the
      absorption energy of Ce3+ to Eu2+. It was due to the spectral overlap between the
      photoluminescence excitation spectrum of Ce3+ and the PL spectrum of Eu2+.
      Moreover, the energy transfer rate from Ce3+ to Eu2+ is generally faster than the
      emission rate of Ce3+ in the dipole-dipole interaction. Depending upon the amount
      of Ca2+ substituted into Sr site, their maximum wavelength was varied from -460
      to -540 nm in terms of the crystal field effect confirmed by the structural
      analysis via Rietveld refinement method. Finally, the optimized blue-emitting
      SMS:Eu2+ and Ca(2+)-substituted yellowish green-emitting SMS:Eu2+ phosphors were
      applied with Eu(2+)-sensitized red-emitting Ca3Mg3(PO4)4:Mn2+ phosphor introduced
      in our previous research to UV light emitting diode (LED)-pumped white LEDs. The
      fabricated white LEDs showed a natural white light with the color coordinate of
      (0.3298, 0.3280) and the excellent color rendering index of 94.

PMID- 23862452
TI  - Influence of water on room-temperature preparation of silver nanoparticles using
      poly(vinyl pyrrolidone) as reducing agent.
AB  - Silver nanoparticles (Ag NPs) were prepared via a wet-chemical method in the
      presence of poly(vinyl pyrrolidone) (PVP) without other reducing agents at room
      temperature. The influence of the addition of water on the preparation of Ag NPs
      was investigated. It was found that water addition has a significant influence on
      the reduction reaction, resulting in changes of shape, size and optical
      properties of the particles. When large amounts of water were added, the
      reduction rate was very slow. However, when small amounts of water were used, the
      opposite effects on the reaction process were observed, initial inhibition effect
      and final promotion effect. Two main possible mechanisms were proposed to explain
      the opposite effects of two reaction stages with small amounts of water addition:
      (1) the initial inhibition effect was induced by free oxygen in water, which
      would react preferentially with the reducing species in the system; (2) the
      promotion effect thereafter may be due to the differences of chain extension of
      PVP molecules and electron transfer rate in ethanol and water.

PMID- 23862453
TI  - Pronounced multiferroicity in oleic acid stabilized BiFeO3 nanocrystals at room
      temperature.
AB  - We report on the experimental observation of pronounced multiferroicity in BiFeO3
      nanocrystals (size approximately 40 nm) at room temperature. Large scale BiFeO3
      nanocrystals are synthesized using a low temperature chemical route and further
      stabilized with oleic acid. The nanocrystals exhibit a significant distortion in
      lattice parameter c compared to the bulk. Oleic acid plays an important role in
      reducing oxygen vacancies and Fe2+ ions at the nanocrystal surface giving rise to
      a high resistivity (approximately 10(10) omega-cm at 300 K) of the sample. The
      direct band gap of nanocrystals is measured to be approximately 4.2 eV (about 1.5
      times the bulk value) suggesting a strong quantum confinement effect. The
      nanocrystals show a remarkably high spontaneous saturation magnetization
      approximately 4.39 emu/g along with a prominent ferroelectric hysteresis loop at
      room temperature. Particle size effect leading to the appearance of large number
      of uncompensated spins and suppression of modulated spin structure have resulted
      a strong spontaneous magnetization in such nanoscale multiferroic materials.

PMID- 23862454
TI  - Electrical properties of Ta(Si)N films prepared by atomic layer deposition from
      tert-butylimido-tris-diethylamido tantalum, silane and hydrogen plasma.
AB  - Ta(Si)N films were prepared by atomic layer deposition (ALD) from tert-butylimido
      tris-diethylamido tantalum (TBTDET), triethylsilane, and activated hydrogen.
      Triethylsilane was used as an ancillary reducing agent and as a silicon
      precursor. The effects of the addition of the triethylsilane at different
      hydrogen plasma pulse times and power on the electrical properties, particularly
      stability in air, were investigated. Longer plasma pulse times with high power
      were effective in decreasing resistivity and increasing stability in air.
      However, introduction of silane resulted in an increase in resistivity of the
      films regardless of the hydrogen plasma conditions.

PMID- 23862455
TI  - Significant enhancement of Sm3+ photoreduction in halide nanophase precipitated
      AIF3-based glasses under femtosecond laser irradiation.
AB  - The electronegativity effect for the efficient photoreduction of Sm3+ to Sm2+ in
      Br-modified fluoroaluminate glasses was investigated after femtosecond laser (fs)
      irradiation. Sm2+ luminescence was strongly observed in the higher Br-modified
      samples, and basing on the TEM and DSC measurements, BaBr2 nanophases were
      precipitated from the glass matrix in the laser focused areas. From the EDS
      spectra, it was found that Sm3+ can be selectively incorporated into the BaBr2
      nanophases. More electrons provided by the nanophase facilitated the Sm3+
      reduction in the irradiation process. Since the photoreduction efficiency of Sm3+
      in Br-modified glass is evidently higher than that in Cl-modified glasses, the
      effect of halide ions electronegativity on Sm3+ photoreduction was identified and
      relevant mechanism was discussed.

PMID- 23862456
TI  - Preparation of iron-doped titania from flocculated sludge with iron-titanium
      composite coagulant.
AB  - The main drawback of flocculation process with dye wastewater is the large amount
      of unrecyclable sludge which needs disposal. A novel process using Ti-salt
      flocculation to purify wastewater was developed to produced sludge that can be
      calcined to produce titania. In this study, iron-doped TiO2 nanomaterial was
      successfully produced from sludge obtained by the flocculation of dye wastewater
      with a composite floculant including TiCl4 and FeSO4. The titania was
      characterised using scanning electron microscopy (SEM/EDX), transmission electron
      microscopy (TEM), X-ray diffraction (XRD), and the photodecomposition of
      acetaldehyde. The XDR results showed that the anatase and rutile structures were
      found after sludge calcination at 550 degrees C and 640 degrees C respectively.
      The elemental analyses were carried out using EDX. The rutile titania sample
      consisted of Ti (35.7 wt.%), Fe (14.7 wt.%), O (42.3 wt.%), P (2.6 wt.%) and Ca
      (4.7 wt.%). The photocatalytic activity was monitored for the photodecomposition
      of gas acetaldehyde. Iron-doped titania seems to play an important role in
      increasing the photocatalytic activity under UV light irradiation.

PMID- 23862457
TI  - Formation process of TiO2 nanotube arrays prepared by anodic oxidation method.
AB  - TiO2 nanotube array thin films have great potential in many fields, such as solar
      cell, photo catalyst, photo-induced cathodic protection for metals and
      bioactivity. In order to investigate the formation process of the TiO2 nanotube
      array thin films, the EIS spectrum and current density were measured during the
      anodic oxidation. The results showed that the formation process could be divided
      into four stages. The current density decreased sharply at the first stage, and
      then increased at the second stage, followed by declining and finally remained
      constant value. In addition, the current density increased with the anodic
      voltage. The EIS spectrum varied in different stage. The simulated circuit was
      composed three sections, the first sections indicated the resistance of the
      electrolyte, the second one gave the double layer structure between the
      electrolyte and titanium electrode, the third one was a inductive loop, which
      represented the anions absorbed on the surface of the TiO2 nanotube's wall. The
      more cations were absorbed, the higher value of the inductive loop would be. The
      EIS results showed that the value increased with the outer voltage, which means
      that more cations were absorbed under the higher anodic voltage.

PMID- 23862458
TI  - Facile synthesis of hierarchical hollow mesoporous Ag/WO3 spheres with high
      photocatalytic performance.
AB  - Hollow mesoporous tungsten trioxide spheres (HMTTS) have been synthesized by
      spray drying method combined with proper calcination and Ag/HMTTS are prepared on
      the basis of a silver mirror reaction. HMTTS are composed of nanoparticles with
      diameter of 20-70 nm. The accumulation of nanoparticles generates pores with the
      mean pore size of about 45 nm. The formation mechanism of hollow mesoporous
      structure is studied in this work. Ag in WO3 narrows the band gap and derceases
      the recombination possibility of the photogenerated electron-hole pairs, which
      enhance photocatalytic activity of Ag/WO3 composites. The degradation rate of
      methylene blue is 98.16% under UV light illumination for 75 min and 49.07% under
      visible light irradiation for 150 min by Ag/WO3 composites.

PMID- 23862459
TI  - Microstructure and physical properties of two charge density wave states in NbSe3
      nanowires.
AB  - The whisker-like niobium triselenide (NbSe3) nanowires were synthesized using the
      traditional solid state reaction. X-ray diffraction experiment suggested the
      monoclinic structure (P2(1)/m), and crystal morphology analysis indicated that
      the band-like shape is the stable morphology. Two charge density wave (CDW)
      states were observed at around 140 K and 50 K, respectively, and the nonlinear
      effect was detected in the CDW states from the R-T and I-V measurements. The
      doped Fe atoms, as pinning centers, play an important role in the nonlinear
      properties of the CDW state. Electron diffraction and HRTEM experiments were
      carried out at different temperatures in order to investigate the structural
      features and their evolution. The sets of incommensurate modulation spots with
      modulation vector q1 - (h, k +/- 0.243, l) appeared below 145 K, and other sets
      of complex superstructure spots with modulation vector q2 - (h, k + 0.3, l +
      1.3424), q3 - (h, k - 0.3137, 1.5685), q4 = (1/3, k, 1) and q5 = (0.5, 0.25, 0.5)
      were observed at [1 0 0] and [3 0 1] zone axis at about 20 K, respectively,
      suggesting the complex incommensurately modulated structures in this material.

PMID- 23862460
TI  - Fabrication of perforated micro/nanopore membranes via a combination of
      nanoimprint lithography and pressed self-perfection process for size reduction.
AB  - Artificial membranes with perforated nanopores in defined locations provide an
      important biomimicking platform for sensing and analysis of biomolecules. This
      study presents a simple and flexible method to fabricate a freestanding polymer
      membrane with perforated micro- and nanopores using a combination of nanoimprint
      lithography (NIL) and pressed self-perfection (PSP) process. NIL was used to
      define initial pores of a few micrometers in diameter in the SU-8 membrane layer,
      which was followed by the PSP process where the patterned SU-8 membrane is
      pressed with a blank silicon wafer at an elevated temperature. This PSP process
      results in a lateral flow of the SU-8 resist and consequently reduces the pore
      size in the membrane. With this method, we have demonstrated fabrication of a SU
      8 membrane with perforated pores down to approximately 300 nm in diameter. The
      results indicate that by employing a pore reduction process nanopore membranes
      can be manufactured without requirements of having a stamp with nanoscale
      structures and high aspect ratio imprinting with the stamp.

PMID- 23862461
TI  - Negative differential resistance and photovoltaic phenomena observed in
      nanostructured organic heterojunction.
AB  - Single layer organic photovoltaic devices based on copper phthalocyanine (CuPc)
      sandwiched between indium tin oxide (ITO) coated glass substrate and aluminum
      (Al) electrode have been fabricated. The interface dipoles formed at the
      metal/organic interface play a key role in determining the barrier for charge
      (electron or hole) injection between the metal electrode and significantly
      affects the efficiency of organic based electronic and optoelectronic devices.
      The origin of interface dipoles formed at the metal/organic (Al/CuPc) interface
      is assumed to be the charge transfer process between the organics (CuPc) and the
      metal (Al) electrode. Such a device shows forward rectifying property under dark
      condition when ITO kept at positive bias and Al kept at negative bias. Negative
      differential resistance (NDR) effect has been observed at high reverse bias
      voltage. Under white light excitation the device shows reverse rectifying
      property with a high open circuit voltage. It appears that the interface dipoles
      formed at the Al/CuPc junction act as exciton dissociation centers. NDR effect
      can be explained due to charge accumulation layer at the AI/CuPc interface and
      hence interface dipoles and/or band bending in CuPc. Asymmetry in dark current
      voltage (I-V) characteristics has been explained due to strengthening or
      weakening the dipole field on the application of reverse bias or forward bias at
      the junction interface, respectively. Various photovoltaic parameters have been
      calculated from the I-V characteristics of the devices under illumination through
      ITO electrode.

PMID- 23862462
TI  - One-pot synthesis of carbon-coated SnO2 nano-composite using hydrothermal method
      for lithium ion battery application.
AB  - Carbon-coated SnO2 nano-composite was synthesized by using a hydrothermal method
      in a one step process with sizes of 1 to 3 microm. The carbon-coated SnO2 nano
      composite was easily obtained by changing firing atmosphere from air to argon
      (600 degrees C for 3 hours). The carbon-coating thickness and size of the SnO2
      nanoparticles in carbon-coated SnO2 nano-composite were confirmed through a high
      resolution transmission electron microscopy (HRTEM) as 40 and 5 nm, respectively.
      Carbon-coating and particle size affect to the capacity retention property.
      Carbon-coated and non carbon-coated samples were investigated as anode materials.
      It was confirmed that the non carbon-coated SnO2 nano-composite had a 718 mA h/g
      initial charge capacity, 91% reached to theoretical value of SnO2 (790 mA h/g),
      while the carbon-coated SnO2 nano-composite had an excellent capacity retention
      of 89.6% after 70 cycles (10.88% for non carbon-coated SnO2 nano-composite).

PMID- 23862463
TI  - Toluene decomposition by DBD-type plasma combined with metal oxide catalysts
      supported on ferroelectric materials.
AB  - We investigated toluene decomposition with a single-stage plasma catalytic system
      operated at atmospheric pressure and working at reduced temperature (T < 75
      degrees C), where a synergistic catalyst was integrated on ferroelectric BaTiO3
      beads with a high dielectric constant. The catalyst species were characterized by
      FE-SEM and XPS before and after the experiment. The MnO2/BaTiO3 catalyst showed
      high stability in igniting plasma during destruction of toluene for 230 hours in
      a lifetime test.

PMID- 23862464
TI  - Spark plasma sintered Ni-YSZ/YSZ bi-layers for solid oxide fuel cell.
AB  - Ni-YSZ/YSZ bi-layers for SOFCs were fabricated by spark plasma sintering (SPS).
      Optimization of SPS parameters of YSZ and NiO/YSZ powders was performed in order
      to fabricate anode and electrolyte with desired microstructures. The effect of
      sintering conditions on microstructure and electrical properties of YSZ was
      studied. The influence of processing parameters and amount of pore-forming agent
      on the microstructures of Ni/YSZ cermets was also investigated. It was shown that
      the amount of pore-former and in situ reduction of nickel oxide had a substantial
      effect on microstructure of the cermets. The in situ reduced anode demonstrates
      sufficiently homogeneous distribution of Ni and YSZ making a conduction path for
      electrons and ions. Ni-YSZ/YSZ bi-layers with crack-free and well-bonded
      anode/electrolyte interface were obtained. Furthermore, warping was not observed
      for the produced bi-layers.

PMID- 23862465
TI  - Layer-by-layer self-assembled carbon nanotube electrode for microbial fuel cells
      application.
AB  - Anodic material is usually a limiting factor in power generation in microbial
      fuel cell (MFC). A meditatorless two-chambered MFC was constructed using new type
      of carbon nanotube (CNT)-based electrode architecture by layer-by-layer (LBL)
      self-assembly to increase power density. Multi-walled carbon nanotube (MWNT) and
      polyeletrolyte polyethyleneimine (PEI) were employed to modify carbon paper (CP)
      electrode utilizing a LBL self-assembly technique, and the electrochemical
      properties and performance of the modified electrode as an anode in MFC were
      investigated. The CNT-based LBL self-assembled electrode showed a better
      electrochemical performance than that of unmodified CP electrode. The self
      assembled MWNT/PEI onto CP produced the maximum power density of 480 mW/m2, which
      was 48% larger than that of the plain CP anode. The CNT-based LBL self-assembled
      electrode therefore offers good prospects for application in MFCs.

PMID- 23862466
TI  - Synthesis of NaYF4, NaLuF4 and NaGdF4-based upconversion nanocrystals with hydro
      (solvo) thermal methods.
AB  - Serials of NaYF4, NaLuF4 and NaGdF4-based nanocrystals have been synthesized
      successfully by solvothermal and hydrothermal, respectively. The properties of
      the products were characterized and compared. The nanocrystals prepared by
      hydrothermal method exhibited uniform hexagonal phase and large size, while the
      nanocrystals prepared by solvothermal method displayed high upconversion
      luminescence (UCL) and small size. The UCL intensities of the nanocrystals
      prepared by solvothermal method were higher than that of nanocrystals from
      hydrothermal method. Whether using solvothermal or hydrothermal method, the UCL
      intensities of the nanocrystals were in the sequence (from strong to weak) of
      NaLuF4:Gd/Yb/Tm, NaLuF4:Yb/Tm, NaGdF4:Yb/Tm, NaYF4:Gd/Yb/Tm and NaYF4:Yb/Tm,
      respectively. This is the first time to systematically compare three kinds of
      host-based nanocrystals, which are prepared by two different approaches with
      various lanthanide ions doped. This work could provide new insight into
      fabrication of upconversion nanocrystals with intense UCL and controllable
      morphology and size via using suitable doping ions, host materials and efficient
      approaches.

PMID- 23862467
TI  - Quartz crystal microbalance sensor coated with nano-sized polystyrene latex
      spheres for SO2 detection.
AB  - In order to investigate the effect of surface morphology on the sensing
      performance in detecting sulfur dioxide, two different types polystyrene,
      polystyrene latex spheres (PLS) and polystyrene film (PSF), are synthesized by
      using an emulsion polymerization, which are coated on quartz crystal microbalance
      (QCM) surfaces. It is found that the sensing performance is strongly dependent on
      the morphology of polymer materials. The adsorption capacity of the synthesized
      PLS is higher than that of the PSF. In addition, the response of the PLS coated
      QCM to SO2 is approximately 6 times faster than that of the PSF coated one. The
      adsorption characteristics of SO2 on the PLS coated QCM are also evaluated in
      terms of temperature and concentration. These results show that the PLS can be
      used as SO2 sensor materials due to their high sensitivity and quick response.

PMID- 23862468
TI  - Facile growth and characterization of TiO2 nanoparticles for photocatalytic
      degradation of 2,3-dichlorophenol: experimental optimization and comparison with
      commercial TiO2.
AB  - This paper reports the facile synthesis and characterizations of TiO2
      nanoparticles by simple sol-gel ultrasonication followed by annealing process.
      The prepared nanoparticles were characterized in terms of their morphological and
      structural properties and utilized as efficient photocatalyst for the
      photocatalytic degradation of 2,3-dichlorophenol (2,3-DCP). The as-synthesized
      TiO2 nanoparticles were annealed at 350 degrees C for various time intervals (3-5
      h) and by morphological and photocatalytic performances, it was found that the
      nanoparticles annealed for 5 hrs exhibits best morphological and photocatalytic
      properties. To optimize the photocatalytic reaction parameters, several
      experiments based on catalyst dose (0.25-1.00 g/L), pH of the solution (pH = 3
      11) and initial concentration (10-100 mg/L) have been performed using
      commercially available TiO2 (PC-105). Under optimized conditions, the
      photocatalytic performance of synthesized TiO2 nanoparticles and TiO2 (PC-105)
      was compared and it was found that the synthesized nanoparticles exhibits better
      photocatalytic properties as compared to the commercially available TiO2 (PC
      105).

PMID- 23862469
TI  - The optical properties of gold nanoparticles with dopamine at different hydrogen
      ion concentration.
AB  - In this work, gold nanoparticles (Au NPs) were prepared by citrate reduction
      method, and the Surface-Enhanced Raman Scattering (SERS) intensities of these
      colloidal solutions with dopamine (DA) were compared at different hydrogen ion
      concentration (pH). The charged states of Au NPs and DA molecules at different pH
      were critical factors for the SERS intensity by affecting NPs aggregation degree
      via DA bridging-effect. The results showed that the SERS enhancement was
      strongest at intermediate pH ranges (pH 7-9), in which the Au NPs was
      sufficiently stable and the electrostatic interaction between the Au NPs and the
      DA molecules was appropriate, together with a slightly aggregating.

PMID- 23862470
TI  - Influence of applied voltage on anodized TiO2 nanotube arrays and their
      performance on dye sensitized solar cells.
AB  - Highly ordered titanium dioxide (TiO2) nanotube films have been fabricated using
      anodic oxidation at different voltages (10 V to 70 V). The morphology, specific
      surface area, light absorbance capability and conductivity of the obtained films
      have been investigated. The anodized voltage was found to have a crucial
      influence on the morphology, light absorb capability and photo-electrochemical
      properties of the anodized nanotube films. The diameter of the nanotube increases
      linearly with the applied voltage. The nanotube film anodized at 30 V has the
      highest BET (Brunauer-Emmett-Teller) surface area, much more quantity of coated
      sensitizer N719, and the smallest resistance for dye sensitized solar cells
      (DSSC). Back side illuminated DSSC were assembled using these as-anodized
      nanotube films. Pt-FTO, which has a transmittance of about 50%, served as counter
      electrode. The best device based on nanotube films performed at 30 V gives a
      highest power conversion efficiency of 1.87%, with a photocurrent density (J(SC))
      of 6.70 mA/cm2 and open circuit voltage (V(OC)) of 0.57 V.

PMID- 23862471
TI  - Transparent films for heterojunction Si photovoltaics.
AB  - A heterojunction of Al-doped ZnO (AZO) and Si was applied as a photodiode. A Co
      sputtering system was used to deposit a quality AZO film following an n-type Si
      thin film coating. Al is an n-doping element for ZnO and thus the Al content
      significantly controls the mobility and the crystalline structure of AZO films.
      In order to provide the highest mobility, the optimum Al-content was found to be
      5.22 wt%. X-ray diffraction analysis also showed a release of the compressive
      stress for the Al-5.22 wt% AZO film. Due to the excellent electrical conductivity
      of the AZO film, the heterojunction diode showed an enhanced rectifying ratio of
      87.7 from 59.9 of the bare Si diode according to the reduction of the series
      resistance. This scheme may provide a route to reducing the contact resistance
      and subsequently improving photovoltaic devices.

PMID- 23862472
TI  - Role of electrical conductivity of spinning solution on enhancement of
      electrospinnability of polyamide 6,6 nanofibers.
AB  - Optimal conditions for electrospinning of uniform polyamide 6,6 (PA66) nanofibers
      were determined by the control of various parameters, such as polymer solution
      concentration, flow rate, tip-to-collector distance (TCD), applied voltage, and
      electrical conductivity of the polymer solution. An organic salt, benzyl
      trimethyl ammonium chloride (C10H16CIN, BTMAC), was added to the solutions for
      increase of electrical conductivity. When no salt was added to the PA66 solution,
      the uniform nanofibers were electrospun only at limited conditions, such as flow
      rate of 0.5 mL/h and electric fields greater than 2.0-3.5 kV/cm. In contrast, by
      the addition of BTMAC, range of optimal conditions for uniform nanofibers was
      expanded; uniform nanofibers were obtained at flow rate of 0.5-1.5 mL/h and
      electric fields greater than 1.3-1.6 kV/cm. This means that the
      electrospinnability of the nanofibers is improved by increasing electrical
      conductivity of the solutions. Furthermore, the addition of BTMAC affected the
      increasing of number average diameters and standard deviation of the nanofibers.
      On the other hand, the process variables, such as flow rate, TCD, and applied
      voltage, exerted little influence on the increase of diameters.

PMID- 23862473
TI  - Color-stable white-light-emitting diodes doped with phosphorescent dopants via
      enhanced energy transfer through homogeneous morphology.
AB  - We demonstrate that white light-emitting diodes using polyfluorene-based blue
      emitting conjugated copolymer and small molecule as co-host doped with green and
      red-emitting phosphorescent dyes. The energy transfer from co-host to
      phosphorescent dyes is enhanced by blending with small molecule due to the
      suppressed phase separation between conjugated polymer and Ir complexes as well
      as the high triplet state of co-host. We obtained voltage-independent pure white
      light emission with homogeneous morphology in the blended single active layer
      system by reducing charge trapping in Ir complexes and enhancing the efficient
      Forster energy transfer.

PMID- 23862474
TI  - Thermal evolution characterizatics of atomic layer deposition prepared TiO2
      interfacial layer by synchrotron radiation X-ray scattering.
AB  - TiO2 thin film prepared by the atomic layer deposition (ALD) with supplies of
      Ti(O-i-Pr)4 and H2O have been analyzed using the difference X-ray reflectivity
      (DXRR). The thickness of buried interfacial layer (IL) embedded in between Si
      substrate and TiO2 layer was characterized as a function of temperatures of 20,
      300, and 500 degrees C mounted on an in-situ hot stage The growth rate of TiO2
      film was estimated to be 0.5 nm/cycle at the temperature of 150 degrees C. It was
      identified that the interfacial layer of the treated thin film was disappeared at
      a certain temperature rise. Furthermore, we found that the crystalline structure
      of TiO2 film was varied depending on not only the growth temperature but also the
      post thermal treatment of the samples. Since the synchrotron radiation X-ray
      scattering measurement allow us to investigate the atomic structure evolution in
      the range of a few nanometer thick, nondestructively, in this letter we report
      its characteristics of the thermal evolution of the TiO2 interfacial layer that
      is the crucial step for progress in microelectronics and nanotechnology.

PMID- 23862475
TI  - Effects of addition of Ta and Y ions to InZnO thin film transistors by sol-gel
      process.
AB  - We have investigated the effects of the addition of tantalum (Ta) and yttrium (Y)
      ions to InZnO thin film transistors (TFTs) using the sol-gel process. TaInZnO and
      YInZnO TFTs had significantly lower off current and higher on-to-off current
      ratio than InZnO TFTs. Ta and Y ions have strong affinity to oxygen and so
      suppress the formation of free electron carriers in thin films; they play an
      important role in enhancing the electrical characteristic due to their high
      oxygen bonding ability. The optimized TaInZnO and YInZnO TFTs showed high on/off
      ratio and low subthreshold swing.

PMID- 23862476
TI  - Enhanced lifetime of organic light-emitting diodes using an anthracene derivative
      with high glass transition temperature.
AB  - Highly stable and efficient phosphorescent organic light-emitting diodes (OLEDs)
      were demonstrated by using anthracene-based hole injection buffer layer
      possessing high glass transition temperature. We synthesized a new anthracene
      derivative, 9,10-bis(3,3'-(N',N'-diphenyl-(N-naphthalene-2-yl)benzene-1,4
      diamine) phenyl)anthracene (TANPA) and characterized its optical and thermal
      properties. It showed high glass transition temperature of 154 degrees C which
      could be attributed to the insertion of anthracene into the aromatic amino group
      with triphenylamine. We also utilized TANPA for the hole injection and transport
      layers in phosphorescent OLEDs. Since TANPA has high glass transition
      temperature, the OLEDs using this material exhibited higher operational stability
      compared to the device without TANPA. When we use TANPA as the hole injection
      layer in combination with a widely-used hole transporting material, N,N'-di(1
      naphthyl)-N,N-diphenylbenzidine (NPB), the devices showed high enhancement in
      terms of the operational lifetime, driving voltage change, and device efficiency,
      originating from the electron-hole charge balance as well as good thermal
      stability of TANPA.

PMID- 23862477
TI  - Density functional theory study on the interactions between Ni(n) (n = 1,..., 6)
      and methylamine or acetic acid.
AB  - The interactions between methylamine or acetic acid with the Ni(n) (n = 1,...,6)
      in triplet clusters were examined at the B3LYP/6-31G(d, p) and LANL2TZ+ level.
      The structural stability, interacting strength and the charge transferring
      properties of the different interacting complexes were studied. The stable
      distance between the Ni(1) and the nitrogen or oxygen is about 2.00 or 1.95
      angstroms for the Ni(n)-CH3NH2 or Ni(n)-CH3COOH, respectively. The results
      indicate that the interacting energy is -27.385 approximatley -134.269 and 
      18.379 approximately -55.136 kJ/mol for the Ni(n)-CH3NH2 and Ni(n)-CH3COOH,
      respectively. The effective electron transfer processes for the Ni(n)-CH3NH2 or
      Ni(n)-CH3COOH is from the lone pair of the nitrogen to the lone pair anti-bonding
      orbital of the Ni(1) or from the oxygen lone pair to the sigma antibonding
      orbitals of Ni(1)-Ni and the sigma anti-bonding orbital of the Ni(1) lone pair,
      respectively.

PMID- 23862478
TI  - Microemulsion-mediated solvothermal synthesis and photoluminescent properties of
      europium tungstate nanostructures.
AB  - The controlled synthesis of Eu2(WO4)3 nanostructures with different morphologies,
      namely ellipsoidlike, rodlike, cubelike, rod-bundlelike, and mesoporous
      spindlike, has been successfully achieved by the cationic surfactant-CTAB
      (cetyltrimethylammoniumbromide)-microemulsion-mediated and anionic surfactant-SDS
      (sodium dodecyl sulfate)-microemulsion-mediated solvothermal method separately.
      Various comparison experiments showed that fundamental experimental parameters,
      such as the water content, reaction temperature and the type of surfactants
      played important roles in the morphological control of Eu2(WO4)3 nanostructures.
      The possible growth mechanisms of these nanocrystals were elucidated in detail.

PMID- 23862479
TI  - Synthesis of CdSe quantum dots using various long-chain fatty acids and their
      phase transfer.
AB  - Monodispersed colloidal photoluminescent CdSe quantum dots (QDs) were synthesized
      via an organic approach by using cadmium oxide and elemental selenium as
      precursors, and long-chain fatty acids as surface ligands. The hydrocarbon chain
      length of the fatty acid was adjusted to investigate the effect on CdSe QDs. The
      fatty acid ligands with different hydrocarbon chain lengths showed an apparent
      effect on the nanocrystal nucleation and growth which is the key controlling the
      size, size distribution and crystal structure of resulting CdSe QDs. This effect
      was attributable to the steric hindrance of different hydrocarbon length of the
      fatty acids, which affected the reactivity of the monomers and nanocrystals
      during the nanocrystal nucleation and growth. The water-soluble CdSe QDs were
      obtained by encapsulating the CdSe ODs in oil phase with amphiphilic poly(styrene
      co-maleic anhydride) (PSMA)-ethanolamine (EA) polymers, which made it possible
      for further applications of the CdSe QDs in aqueous environment such as surface
      functionalization for biological labeling and application in photocatalysis and
      photosensitization.

PMID- 23862480
TI  - Scalable alignment of CdS nanowires based on efficient roll-on transfer
      technique.
AB  - A roll-on transfer strategy is developed to enable large-scale and uniform
      assembly of CdS nanowires on various rigid and flexible substrate materials. In
      this method, the CdS nanowires were synthesized by the hydrothermal method. The
      dispersed CdS NWs could be firstly aligned and selectively deposited at the
      micro/nanochannels between aligned nanofibers on the surface of the donor roller
      as a result of evaporation-induced flow and capillary action, and then the
      directional and aligned transfer of the CdS NWs from the donor roller to a
      receiver substrate via roll-on transfer technique. Finally, a device structures
      consisting of the nanowire channel and two metal electrodes was fabricated. The
      electrical property of this device was observed.

PMID- 23862481
TI  - CuZn dendritic alloys: their template-free electrochemical preparation and
      morphology-dependent wettability.
AB  - In this paper, we report a preparation of CuZn dendritic microstructures through
      a tunable template-free electrochemical approach. By simply tunning the applied
      depositing current, the morphology of the product can be well controlled. The
      growth mechanism of CuZn dendritic alloys was also verified. The experimental
      results suggest that the growth of the grass-like structures obtained at 5 mA is
      driven by diffusion limited aggregation, while the driving force of the formation
      of CuZn dendrites obtained at 10 mA and 15 mA is gas bubbling worked as the
      dynamic template. The contact angle test shows the modified CuZn dendritic
      products possess superhydrophobic property. Additionally, through annealing of
      CuZn alloys in argon as the protective gas, derivative Cu/ZnO composite materials
      can be produced.

PMID- 23862482
TI  - Effect of transition metal dopants on mechanical properties and biocompatibility
      of zirconia ceramics.
AB  - In this study, the effect of transition metal dopants, originally added as
      colouring agents, on the mechanical properties and biocompatibility of sintered
      zirconia was investigated. This study confirmed that transition metal dopants
      could have a slight detrimental effect on the mechanical properties of zirconia.
      The addition of metal dopants did not affect the adhesion and proliferation of
      gingival fibroblasts.

PMID- 23862483
TI  - Fabrication of hierarchical ZnO enriched fibrous PVA membrane.
AB  - We have demonstrated herein a simple method for the fabrication of hierarchical
      structure of ZnO enriched fibrous PVA membrane. The observed result has shown the
      uniform coating of ZnO on the fiber surface. Effective control of the density of
      coating has been brought about by changing the concentration of ZnO and combined
      sol-gel coating. Serving as seeds for the growth of nanorods, the ZnO nuclei
      evolve to form nanorods whose density and length have been controlled by thermal
      treatment. We believe that the methodology described in this report offers a
      simple and straightforward route to prepare the hybrid structure and furthermore
      find an exercise in various optoelectronic fields.

PMID- 23862484
TI  - Fabrication of porous noble metal thin-film electrode by reactive magnetron
      sputtering.
AB  - Porous platinum films have been fabricated by reactive sputtering combined with
      subsequent thermal annealing. Using the SEM, XRD, XPS, and polarization
      resistance measurement techniques, the microstructural development of the film
      and its resultant electrochemical properties have been characterized. Pore
      evolution was understood as a result of the thermal grooving of platinum during
      annealing process. We demonstrated that crystallization should be followed by
      agglomeration for the evolution of porous microstructures. Furthermore, reaction
      sputtering affected the adhesion enhancement between the film and substrate
      compared to the film deposited by non-reactive sputtering. The polarization
      resistance of the porous platinum film was five times lower than that of the
      dense platinum film. At 600 degrees C the resistance of the porous film was 5.67
      omega x cm2, and that of the dense film was 38 omega x cm2.

PMID- 23862485
TI  - Synthesis and characterization of monodispersed core-shell/polystyrene-silica
      composite nanospheres as artificial dusts.
AB  - Monodispersed core-shell/polystyrene-silica composite nanospheres are synthesized
      as artificial dusts by a two-step process, the preparation of seed copolymer
      spheres and the formation of a silica layer on the seed spheres. The poly(styrene
      co-MPS) copolymer spheres containing silanol groups are first prepared by
      emulsion polymerization using 3-(trimethoxysilyl)propyl methacrylate (MPS) as a
      co-monomer, potassium persulfate (KPS) as a initiator, and sodium dodecyl sulfate
      (SDS) as a stabilizer. The diameter of the copolymer spheres is in the range of
      220-270 nm with very small coefficients of variation (CV), depending on the
      content of MPS. The thermal property of the copolymer spheres is also improved as
      the content of silica increases. Later a silica layer is formed on the seed
      copolymer spheres by a reaction with tetraethylorthosilicate (TEOS) in aqueous
      solution. The thickness of the silica layer formed is about 4 to 10 nm, which
      greatly improves the thermal stability of the copolymer spheres.

PMID- 23862486
TI  - Heuristics-assisted combinatorial screening of oxynitride phosphors.
AB  - Nitride or oxynitride phosphors have been recently acting as key phosphors in the
      light emitting diode (LED) application. In particular, their superiority to the
      conventional oxide-based phosphors in terms of efficacy, thermal stability, color
      rendering, and etc. made it possible to achieve rapid commercialization of
      several nitride or oxynitride phosphors such as CaAISiN3, alpha- and beta
      Sialons, Sr2Si5N8, and etc. However, it is still necessary to discover more
      nitride or oxynitride phosphors, which meet specific requirements for LED
      applications. In this regard, heuristics-based combinatorial material search
      (HCMS) strategies have been applied to multi-compositional inorganic systems to
      search for new phosphors and to optimize the properties of phosphors in the six
      dimensional SrCO3-BaCO3-CaCO3-SiO2-Si3N4-Eu2O3 search space. The heuristics
      strategies include non-dominated sorting genetic algorithm (NSGA) and particle
      swarm optimization (PSO).

PMID- 23862487
TI  - Fabrication and characterization of core-shell structured black pigment particles
      for electrophoretic display.
AB  - To prepare electrophoretic black particles with good suspension stability in the
      low dielectric medium for the electrophoretic display application, black pigment
      (B444) as a core material and polystyrene (PS) as a shell material were prepared
      via dispersion polymerization of styrene, and then the fabricated B444/PS
      composite particles were positively charged with 2-(methacryloyloxy) ethyl
      trimethylammonium chloride. Morphology of the B444/PS core-shell particles was
      observed by scanning electron microscopy, while their chemical structure was
      confirmed via an FT-IR. Maximum values of the electrophoretic mobility and zeta
      potential observed by dynamic light scattering reach 4.46 x 10(-6) m2/Vs and
      30.23 mV in a low dielectric medium, respectively. The resulting B444/PS
      particles also showed good electrophoretic movement in the B444/PS particle
      embedded microcapsules. Therefore, it can be applied in the dual-particle
      electrophoretic dispersion together with negative charged TiO2, showing black and
      white images.

PMID- 23862488
TI  - The influence of doped iron oxide on the performance of ceria-based solid
      electrolyte.
AB  - The research of ceria-based electrolyte is of great significance for application
      of medium or low temperature solid oxide fuel cells. In this paper, Ce0.8Gd0.2O(2
      delta) (CGO) and CGO doped with 2.0 mol% FeO1.333 (2Fe-CGO) were synthesized by
      low-temperature combustion method, and the effects of doped iron oxide on density
      and conductivity were studied. The experimental results indicated that the
      relative density of 2Fe-CGO increased within a certain temperature range due to
      the occurrence of viscous flow sintering. It was found that Fe3O4 could clear
      SiO2 impurities in the grain boundary, which can greatly enhance the conductivity
      of 2Fe-CGO. The conductivity of 2Fe-CGO was two orders of magnitude larger than
      CGO's when the test temperature was 250 degrees C.

PMID- 23862489
TI  - Reduction process of dislocation and standby leakage current for embedded flash
      memory using nano-scale integration.
AB  - We determined that the use of densification, sacrificial oxidation, gate
      oxidation and source/drain implantation has the capability to reduce the
      dislocation. A dislocation-free process is proposed, and its mechanism presented
      in embedded flash memory. The dislocation decreased when n-type ions were
      implanted at a low energy level for source and drain. A dry oxidation process
      using only oxygen without hydrogen and oxidation for logic gates led to the
      formation of a sacrificial oxide on the rapid thermal oxidation (RTP) methods
      without densification after gap-filling as reducing dislocation processes. These
      methods dramatically reduced the standby leakage current.

PMID- 23862490
TI  - Solvothermal synthesis of hollow urchin-like SnO2 nanospheres with superior
      lithium storage behavior.
AB  - Hollow urchin-like SnO2 nanospheres with ultrathin nanorods have been
      successfully synthesized via a simple complex solvothermal route. The formation
      mechanism of the as-synthesized SnO2 nanospheres was simply explained. When
      tested as anode, the as-obtained hollow urchin-like SnO2 nanospheres exhibit
      excellent rate and cycling performances. It was expected that the as-synthesized
      SnO2 nanospheres could be applied as anode materials for future lithium-ion
      batteries.

PMID- 23862491
TI  - High-aspect-ratio and high-flatness Cu3(SiGe) nanoplatelets prepared by chemical
      vapor deposition.
AB  - Cu3(SiGe) nanoplatelets were synthesized by low-pressure chemical vapor
      deposition of a SiH3C2H5/Ge2(CH3)6 mixture on a Cu-substrate at 500 degrees C,
      total pressure of 110-115 Pa, and Ge/Si molar ratio of 22. The nanoplatelets with
      composition Cu76Si15Ge12 are formed by the 4'-phase, and they are flattened
      perpendicular to the [001] direction. Their lateral dimensions reach several tens
      of micrometers in size, but they are only about 50 nm thick. Their surface is
      extremely flat, with measured root mean square roughness R(q) below 0.2 nm. The
      nanoplatelets grow via the non-catalytic vapor-solid mechanism and surface
      growth. In addition, nanowires and nanorods of various Cu-Si-Ge alloys were also
      obtained depending on the experimental conditions. Morphology of the resulting Cu
      Si-Ge nanoobjects is very sensitive to the experimental parameters. The formation
      of nanoplatelets is associated with increased amount of Ge in the alloy.

PMID- 23862492
TI  - Nanostructure fabricated by nanosphere lithography assisted with O2 plasma
      treatment.
AB  - Nanosphere lithography is an efficient way to fabricate metallic nanostructures
      with large area. This paper presents the fabrication of metallic hexagonal nano
      pyramid arrays by two dimensional nanospheres lithography assisted with O2 plasma
      treatment. By O2 plasma treatment, the gap and diameter of nanospheres can be
      modulated. After electron beam deposition, we can fabricate similar
      nanostructures with different pyramid gap distances. This method may be an easy
      way to modulate the geometric parameters of nanostructures.

PMID- 23862493
TI  - Effect of incorporated PVP/Ag nanoparticles on ZnPc/C60 organic solar cells.
AB  - Various sizes of PVP-capped Ag nanoparticles were incorporated in the PEDOT:PSS
      layer of ZnPc/C60-based small-molecule organic solar cells. The incorporated
      nanoparticles partially block the incident light, but this was offset by the
      scattering effect and consequent increase in path lengths through the active
      organic layers. As a result, the overall power conversion efficiency of the cell
      increased by approximately 15% when nanoparticles with an average diameter of 24
      nm were used.

PMID- 23862494
TI  - Green synthesis of graphene.
AB  - The present work reports a green route to synthesis of graphene by reduction of
      graphite oxide with cocos nucifera L. (coconut water) as reducing agent which is
      naturally available, non-toxic and environmental friendly. The graphite oxide has
      been prepared by oxidation of graphite with KCIO3/NaNO3/H2SO4 as reported in our
      earlier findings. X-ray diffraction, FTIR, UV-Visible and Raman spectroscopy
      confirmed the formation of graphene. SEM, TEM and AFM analyses have also been
      carried out to study the morphological characteristics of the obtained product.
      Also, TG analysis presents the thermal stability behavior of the formed product.
      Zeta potential measurements were also carried out to determine the surface charge
      characteristics.

PMID- 23862495
TI  - High-efficiency GaN-based vertical light-emitting diodes with periodic beveled
      rod-shaped structures.
AB  - The periodic beveled micro-rods (BMRs) were constructed on the emission surface
      of GaN-based vertical light-emitting diodes (VLEDs) in order to improve the light
      extraction efficiency. It was experimentally demonstrated that the light output
      power of the VLEDs with a periodic BMR (BMR-VLED) were enhanced about 15.6%,
      compared with that of the VLEDs with randomly textured surface (RT-VLED) at an
      injection current of 350 mA. This finding indicates that the photons emitted from
      the active layer were well out-coupled at an n-GaN surface having a periodic BMR
      structure, resulting in an increase in the probability of escaping from the VLED
      structure.

PMID- 23862496
TI  - Synthesis and characterization of fluorescence resonance energy transfer-based
      nanoprobes by coating CdTe QDs with rhodamine B in gelatin nanoparticles.
AB  - A FRET-based nanoprobe consisting of CdTe quantum dot as donor and rhodamine B as
      acceptor embedded in gelatin nanoparticles was constructed and the photophysics
      of the system was characterized. The FRET-based sensors were led to at fixed
      donor/acceptor distance by synthesizing via a two-step desolvation way. This
      approach allowed for short acceptor-donor separation and thus for high energy
      transfer efficiencies. The morphology of the nanoprobes was presented spherically
      and relatively uniform with a diameter of about 100 nm, which was characterized
      by transmission electron microscope. The luminescent property was proved to be
      stable in vitro and in living cells, indicating that the nanoprobes can be
      expected to be promising candidates for biological imaging studies.

PMID- 23862497
TI  - Preparation and characterization of Ni-based perovskite catalyst for steam CO2
      reforming of methane.
AB  - Steam CO2 reforming of methane was investigated over Ni-based perovskite catalyst
      to produce desired H2/CO ratio by adjusting the feed ratio of CH4, CO2 and H2O
      for floating GTL process application. La modified perovskites were prepared by
      the Pechini method and calcined in air and the Ni-based catalysts were prepared
      by dispersing Ni on the La modified perovskite by an incipient wetness
      impregnation. The catalysts before and after the reaction were characterized by
      N2 physisoprtion, CO chemisoprtion, XRD, TPR and SEM techniques. To control
      desired H2/CO ratio, simulation for SCR was carried out by Aspen plus, and
      product distribution for SCR was investigated in a fixed bed reactor system using
      feed ratio estimated by simulation. The Ni-based perovskite catalysts were found
      to give CH4 and CO2 conversions of up to 82% and 60% respectively to yield a
      H2/CO product ratio close to 2.

PMID- 23862498
TI  - Electrochemical and optical characterization of cobalt, copper and zinc
      phthalocyanine complexes.
AB  - New phthalocyanine (Pc) derivatives that include the alkyl group in ligand were
      synthesized based on three core metals such as zinc (Zn), copper (Cu), and cobalt
      (Co). Electrochemical behaviors and optical properties of the new phthalocyanine
      derivatives with ligand and different core metal were investigated by using
      cyclic voltammetry, UV-Visible (UV-Vis) spectroscopy and photoluminescence (PL)
      spectroscopy. In UV-Vis data, maximum values of 2H, Co, Cu, and Zn complexes were
      708 nm and 677 nm, 686 nm, 684 nm, respectively.

PMID- 23862499
TI  - Investigation on nanotubular surface structure of Ti-10Nb-10Ta alloy by
      anodization.
AB  - The anodized nanotubular surface structure of a Ti-10wt.%Ta-10wt.%Nb alloy were
      characterized by field emission scanning electron microscopy (FE-SEM), X-ray
      photoelectron spectroscopy (XPS) and depth profiling, and transmission electron
      microscopy (TEM). A highly ordered layer of individual nanotubes approximately
      100 nm in diameter and 600 nm in length was formed. XPS revealed the nanotubes to
      be composed mainly of TiO2. The XPS depth profile suggested that the nanotubular
      surface structure consisted of three zones: (1) a zone containing fluorine
      element, (2) a zone containing oxygen and titanium elements whose concentrations
      changed rapidly, and (3) a zone containing mainly titanium element.

PMID- 23862500
TI  - Cation location in microporous zeolite, SSZ-13, probed with xenon adsorption
      measurement and 129Xe NMR spectrum.
AB  - The location of metal ion, Ag2+, Ca2+, Cu2+ and Y3+ in the SSZ-13 has been
      investigated with xenon adsorption measurement and 129Xe NMR spectrum. It was
      referred that the location of the metal ion varies depending on the corresponding
      charge. The ion-exchanged Ag ion was located in the alpha-cage to interact
      directly with xenon. Others multivalent cation contributed little with xenon
      because these were present near the six membered rings where xenon cannot access.

PMID- 23862501
TI  - Synthesis and characterization of platinum(II) complexes containing spiro system.
AB  - Platinum complexes [Pt(bpy)Cl2](bpy: 2,2'-bipyridine) and [Pt(PT)Cl2](PT: 1,10
      phenantroline) were reacted with 5,5"-(9,9-dioctyl-9H-fluorene-2,7-diyl)bis(2,2'
      bipyrine), bpy-spiro-bpy, to afford mono and diplatinium complexes: [(bpy)Pt(bpy
      spiro-bpy)][PF6]2, [(bpy)Pt(bpy-spiro-bpy)Pt(bpy)])[PF6]4, and [(PT)Pt(bpy-spiro
      bpy)])][PF6]2, which were characterized by NMR, UV/VIS, mass spectrum, and PL
      spectroscopy. They showed very high internal quantum yields (0.35-0.67) and
      emitted light in the blue region (473-520 nm). Herein, we describe the synthesis,
      characterization of the mono- and di-platinum complexes in detail.

PMID- 23862502
TI  - Western blot membrane composed of electrospun polyvinylidene fluoride nanofiber
      membrane and polyethylene terephthalate sheet.
AB  - In a previous study, an electrospun polyvinylidene fluoride (PVDF) nanofiber
      membrane was developed for Western blotting. The membrane exhibited high
      sensitivity and high binding capacity for the detection of protein bands that was
      unlike that observed for conventional, microphase separation-based porous PVDF
      membranes. Nevertheless, the PVDF nanofiber membrane is quite expensive. The
      objective of this study was to develop an economical Western blot membrane using
      a hybrid electrospun PVDF nanofiber and polyethylene terephthalate (PET) sheet.
      The results showed that the detection sensitivity of the 4 gram per square meter
      (gsm) membrane was similar to those of the electrospun PVDF nanofiber membrane
      only, and the 7 gsm PVDF nanofiber membranes on a PET sheet and the electrospun
      PVDF nanofiber membrane. This means the protein detection sensitivity is not
      proportional to the thickness of the PVDF nanofiber membrane. The 4 gsm PVDF
      nanofiber membrane on a PET sheet can be used to detect proteins with high
      sensitivity and economic efficiency.

PMID- 23862503
TI  - Hybrid YAG/CdSe quantum dots phosphors for white light-emitting diodes.
AB  - CdSe quantum dots (QDs) with the emission wavelength of 577 nm, full width at
      half maximum (FWHM) of 28 nm, quantum yield (QY) of 40% and average particle size
      of 3.7 +/- 0.5 nm are prepared. 1, 3 and 5 wt% of CdSe QDs is blended with
      commercial YAG:Ce phosphor (called as composite phosphor) and the device
      performance of YAG-based and composite phosphor-based white light-emitting diode
      (WLED) is investigated. The color rendering index (CRI) and luminous efficiency
      could be improved simultaneous for composite phosphor-based WLED. As the applied
      current increases, the correlated color temperature (CCT), Commission
      International d'Eclairage (CIE) chromaticity coordinates and CRI of both WLEDs
      are almost the same when compared with standard condition (20 mA), while the
      luminous efficiency of both WLEDs decreases with increasing applied current. It
      is interesting to find that there is a positive effect of QDs on the luminous
      efficiency and CRI value. This result also reveals that adding a small amount of
      yellow emitting QDs can not only reduce the scattering of light effectively but
      increase utilization efficiency of reflection and refraction light, thereby
      enhancing the efficiency of composite phosphor-based WLED. Moreover, the emission
      wavelength of 577 nm QDs is longer than that of YAG, it redound to extends
      emission range resulting in increase the CRI of devices.

PMID- 23862504
TI  - Graphene encapsulated Fe3O4 nanospindles as a superior anode material for lithium
      ion batteries.
AB  - Graphene encapsulated Fe3O4 nanospindles were synthesized by a simple
      hydrothermal method. From field-emission and transmission electron microscopy
      results, the Fe3O4 nanospindles with the length of about 260 nm are highly
      encapsulated in graphene matrix. The reversible Li-cycling properties of graphene
      encapsulated Fe3O4 nanospindles have been evaluated by galvanostatic discharge
      charge cycling and cyclic voltammetry. Results show that graphene encapsulated
      Fe3O4 nanospindles exhibits a high reversible capacity about 745 mA h g(-1) for
      the first cycle and a stable capacity of about 558 mA h g(-1) for up to 200th
      cycle in the voltage range of 0.01-3.0 V at a current density of 100 mA g(-1),
      indicating excellent cycling stability. The graphene in the composite materials
      could act not only as lithium storage active materials, but also as an
      electronically conductive matrix to improve the electrochemical performance of
      Fe3O4.

PMID- 23862505
TI  - Nanoscale SnO2 flat-type coplanar hexanal gas sensor arrays at ppb level.
AB  - Hexanal is one of the most important aroma compounds which play a crucial role in
      the odor of cereal, meat, fruit, plant oils and wood. The detection technique of
      hexanal has attracted more attention. In this paper, the nano-SnO2 flat-type
      coplanar hexanal gas-sensor arrays were fabricated by screen-printing technique
      based on nano-SnO2 powders prepared by hydrothermal method. The test results show
      that the nano-SnO2 flat-type coplanar gas sensor arrays have good hexanal gas
      sensing characteristics, such as low detection limit and high sensitivity.
      Especially, the gas sensitivity of the nano-SnO2 gas sensor arrays to 100 ppb
      hexanal can reach 2.8 at 350 degrees C. The nanometer size effect of nano-SnO2
      and nature property of hexanal caused the ppb-level hexanal gas sensing
      characteristics.

PMID- 23862506
TI  - Characterization and properties of UV-curable hyperbranched polyurethane acrylate
      polyurethane diacrylate/SiO2 hybrid coatings.
AB  - A series of new UV-curable hybrid coatings were prepared with hyperbranched
      polyurethane acrylate-polyurethane diacrylate (HBPUA-PUDA) and organic SiO2 as
      formation, and 2-hydroxyl-2-methyl-l-phenyl-1-propanone (Darocur 1173) was used
      as photo-initiator. The effect of organic SiO2 content on the thermal stability
      and conversion of C=C bonds of the UV-cured HBPUA-PUDA/SiO2 films were evaluated
      using thermal gravimetric analysis (TGA) and Fourier transform infrared
      spectroscopy (FTIR). The morphology of SiO2 were observed by using transmission
      electron microscopy (TEM), field emission scanning electron microscopy (FESEM),
      and the elemental composition of SiO2 was tested by energy dispersive
      spectrometer (EDS). The results revealed that when organic SiO2 content was less
      than 30 wt%, the average particle size of SiO2 was about 95 nm and the particles
      were well-dispersed in the organic phase. The mechanical properties, abrasion
      resistance and transmittance of the films were also investigated. The results
      showed that with the increase of organic SiO2 content, the adhesive force and
      pendulum hardness were increased obviously, while the transmittance and
      flexibility were decreased. When the content of the organic SiO2 was 30 wt%, the
      film of HBPUA-PUDA/SiO2 showed the optimal comprehensive performance as follows:
      pendulum hardness was 0.74, transmittance was 93.1%, adhesion was 0 grade,
      flexibility was 2 mm, impact strength was 43 Kg x cm and mass loss of 300 cycles
      was 12.9 mg.

PMID- 23862507
TI  - Magnetic behavior of Ni nanoparticle films produced by two laser irradiations in
      vacuum.
AB  - Ni Nanoparticle assembled thin films were prepared using an unconventional
      approach based on the use of a secondary nanosecond (ns) ultraviolet (UV) laser
      irradiation interacting with the plume of ablated nanoparticles (NPs) during the
      femtosecond pulsed laser deposition (fs-PLD). The secondary laser beam determines
      the reduction of the NPs size and their dispersion by partial vaporization of the
      NPs during their flight from the target to the substrate. The proper selection of
      the time delay between fs and ns laser pulses allows the latter to interact
      selectively with different parts of the NPs plume, controlling, to a certain
      degree, the reduction of the NPs size and dispersion. Another original effect of
      the UV laser irradiation is the change in the deposited films topology, due to a
      reduction of the NP-aggregates density and size, fostering non-uniform dense
      assemblies of NPs with concentration well above the percolation threshold, with
      the consequent reduction of the influence of the exchange interactions on the
      macroscopic magnetic properties. The magnetic behavior of the films prepared
      using two laser beams with respect to that obtained in the case of fs-PLD only is
      characterized by higher H(c) values (up to approximately 70%) and a good
      compromise between the hysteresis loops squareness and moderate exchange
      interactions, strongly correlated with the NPs topology.

PMID- 23862508
TI  - Color stability of white organic light emitting devices with a color conversion
      layer utilizing CdSe/ZnS quantum dots and phosphors dispersed in
      polymethylmethacrylate.
AB  - White organic light-emitting devices (WOLEDs) were fabricated by combining a blue
      emitting organic light-emitting devices (OLEDs) and a color conversion layer made
      of yttrium aluminum garnet phosphors and CdSe/ZnS quantum dots (QDs) embedded
      into polymethylmethacrylate. When the ratio of phosphors and QDs changed, a good
      color balance was achieved at a ratio of 1:5, and the maximum luminance of 18.21
      cd/m2 was obtained. As the applied voltage varied from 12 to 16 V, Commission
      Internationale de l'Eclairage coordinates shifted only slightly from (0.32, 0.34)
      to (0.30, 0.33), indicating a good color stability.

PMID- 23862509
TI  - Optical properties of white organic light-emitting devices fabricated utilizing a
      mixed CaAl12O19:Mn4+ and Y3Al5O12:Ce3+ color conversion layer.
AB  - White organic light-emitting devices (OLEDs) were fabricated by combining a blue
      OLED with a color conversion layer made of mixed Y3Al5O12:Ce3+ green and
      Ca2AlO19:Mn4+ red phosphors. The X-ray diffraction patterns showed that Ce3+ ions
      in the Y3Al5O12:Ce3+ phosphors completely substituted for the Y3+ ions and the
      Mn4+ ions in the CaAl12O19:Mn4+ phosphors completely substituted for the Ca2+
      ions. Electroluminescence spectra at 11 V for the OLEDs fabricated utilizing a
      color conversion layer showed that the Commission Internationale de l'Eclairage
      coordinates for the Y3Al5O12:Ce3+ and CaAl12O19:Mn4+ phosphors mixed at the ratio
      of 1:5 and 1:10 were (0.31, 0.34) and (0.32, 0.37), respectively, indicative of a
      good white color.

PMID- 23862510
TI  - Preparation and characterization of Cu-based catalysts for methanol synthesis in
      MeOH-FPSO process.
AB  - A series of Cu-ZnO based catalysts have been synthesized by the wet impregnation
      method at different pH, and after calcinations, have been evaluated for the
      synthesis of methanol in the temperature range 220 to 260 degrees C at 35 bar
      with space velocity of 3,000 h(-1) and feed molar ratios of H2/CO = 2. The
      catalysts have been characterized by XRD, SEM, elemental analysis, surface area
      and porosity measurements. It is found that the catalyst synthesized at pH 7 is
      most active with a CO conversion of 35.7% and a methanol selectivity of 98.1% and
      this can be used as an efficient catalyst for the MeOH-FPSO process.

PMID- 23862511
TI  - Preparation of single-site catalyst inside the functionalized nanopore of silica
      and its ethylene polymerization.
AB  - Amorphous silica have been functionalized with organo-silane, and (n-BuCp)2ZrCI2
      and methylaluminoxane (MAO) were subsequently immobilized on the functionalized
      silica for the further evaluation as a catalyst of ethylene polymerization. Four
      organo-silanes such as 3-aminopropyltrimethoxysilane (1NS), N-[(3
      trimethoxysilyl)propyl]ethylenediamine (2NS), N1-[3
      (trimethoxysilyl)propyl]diethylenetriamine (3NS), and 4
      (triethoxysilyl)butyronitrile (1NCy), were employed for this study. The Zr
      content and polymerization activity of the supported catalysts were strongly
      dependent on the kind and structure of organo-silane. 2NS showed the highest Zr
      content with higher activity, indicating the more Zr could be captured due to a
      stronger interaction between (n-BuCp)2ZrCl2 and amine group.

PMID- 23862512
TI  - Remediation of chromium-contaminated water using biogenic nano-sized materials
      and metal-reducing bacteria.
AB  - As an environmental nanotechnology, nano-sized materials have the potential to
      create novel and effective in-situ and ex-situ treatments for contaminated
      groundwater due to its high catalytic reactivity, large surface area, and
      dispersibility. In this study the efficiency of Cr(VI) reduction and
      immobilization using biotic and abiotic nano-sized materials (NSMs) and metal
      reducing bacteria (MRB) was evaluated to remediate Cr(VI)-contaminated
      groundwater in batch and column tests. The results of this study revealed that
      the combination of the mixed MRB and bio-FeS/siderite performed the highest
      efficiency of Cr(VI) reduction and immobilization. Cr(VI) reduction by MRB and
      NSMs could impact on solubility of Cr(VI) and geochemical changes favorable for
      precipitation and adsorption.

PMID- 23862513
TI  - Influence of alkaline mineralizer on structural and optical properties of ZrO2
      nanoparticles.
AB  - In this work, the influence of different alkaline mineralizers on structural and
      optical properties of zirconia nanoparticles synthesized by chemical co
      precipitation technique using zirconium oxychloride octahydrate (ZrOCI2 x 8H2O)
      as precursor is studied. The mineralizers used for the synthesis of nanoparticles
      are NaOH and NH4OH. X-ray diffraction, Fourier Transform Infrared (FTIR)
      spectroscopy, UV-visible absorption spectroscopy and Photoluminescence (PL)
      spectroscopy were used for characterizing the nanoparticles. Structural analysis
      of the sample synthesized using NaOH shows monoclinic phase as predominant one,
      however when NH4OH is used the major phases are cubic and tetragonal. The
      difference is attributed to the number of hydroxyl ions produced and their rate
      of release during the reaction process. The presence of these phases in both
      samples is further confirmed by vibrational bands of FT-IR spectra. Also, the low
      energy bands due to the presence of defects in nanoparticles are also explicitly
      observed in the photoluminescence spectra. Further the defects lead to a red
      shift in the band gap of ZrO2 which is observed when the samples are subjected to
      UV-absorption spectroscopy analysis. It has been demonstrated that zirconia
      nanoparticles with desired structural properties can be synthesized by changing
      the type of mineralizer without the necessity of doping.

PMID- 23862514
TI  - Hierarchical zeolite beta: an efficient and eco-friendly nanocatalyst for the
      Friedel-Crafts acylation of toluene.
AB  - P-Methyacetophenone, the acylated product of toluene finds a wide range of
      applications in the flavors and fragrance industry. It is typically produced on
      an industrial scale by Friedel-Crafts acylation of toluene with acetic anhydride
      using homogeneous, corrosive and polluting acid catalysts such as aluminium
      chloride. The pollution problems related to this process such as the disposal of
      catalyst and treatment of acidic effluent needs to be replaced by a green
      process. The current work reports on the activity of hierarchical zeolite Beta in
      the liquid phase acylation of toluene with acetic anhydride. The liquid phase
      reactions were carried out in the temperature range of 60-140 degrees C in an
      autoclave. The effect of various reaction parameters such as time-on-stream
      (TOS), mole ratio of reactants, catalyst loading, and reaction temperature on the
      rates of reaction has been investigated. Under the optimum reaction conditions
      the performance of hierarchical zeolite Beta was compared with nanocrystalline
      zeolite Beta. It was found that hierarchical zeolite Beta catalyst exhibit higher
      activity, which is due to the hierarchical porosity and to the nano size of the
      Beta zeolite catalyst particles allows faster diffusion of the products out of
      the catalyst.

PMID- 23862515
TI  - In silico analysis the complementarity of tomato microRNA/microRNA* sequences
      with Cucumber mosaic virus (CMV) genomic RNAs.
AB  - Usually, modifications in normal microRNAs (miRs)-dependent gene expression are
      induced in transgenic plants expressing viral silencing suppressors or in viruses
      inoculated plants. These phenomena are generally interpreted as a side effect of
      the antiviral silencing suppression. However, it has been recently reported that
      certain animal miRs prevent viral infection by directly interfering with pathogen
      replication or by binding to viral transcripts. To investigate whether such
      mechanisms operate in plants, we performed in silico analysis using tomato
      miR/miR* sequences and genomes of Cucumber mosaic virus (CMV)-Fny (the severe
      strain), CMV-Q (the mild strain), the aggravated satellite RNA (satRNA) variant
      satT1 and the attenuated variant satYn12. Results showed that a total of 38 and
      37 miR/miR* sequences could bind to genomic RNAs of CMV-Fny and CMV-Q,
      respectively. But only one sequence could bind to safT1 and three to satYn12.
      Interestingly, we found that these miRs/miR*s exhibited significant
      complementarity within 2a and 3a Open Reading Frames (ORFs) of CMV. And most of
      the sequences with potential to bind viral genomes were of miR*s, suggesting
      novel role of miR*s in host defense response. This finding is noteworthy as plant
      miR* sequences are presently thought very unstable and are not assigned with any
      function. Finally, we could predict targets in tomato database for the miR/miR*
      sequences that are highlighted in our study, most of them are involved in plant
      metabolism. Overall, these results shed light on the possible novel role of plant
      miR/miR* in antiviral defense mechanisms.

PMID- 23862516
TI  - The effect of the Nb2O5 dispersion on ethylene vinyl acetate to obtain ethylene
      vinyl acetate/Nb2O5 nanostructured materials.
AB  - This work investigated the effect of niobium pentoxide nanoparticles (Nb2O5) on
      the molecular organization of an ethylene vinyl acetate copolymer (EVA) matrix
      containing 28% vinyl acetate groups, according to their dispersion and
      distribution in the polymer matrix. Due to niobium pentoxide's characteristics
      and properties, it may interfere in the chemical and UV resistance, as well as in
      the EVA mechanical properties, increasing mechanical resistance. The EVA/Nb2O5
      nanocomposite films, with Nb2O5 varying from 0.25 to 1% in relation to the total
      EVA mass, were prepared by solution casting. The Nb2O5 was well dispersed with
      the use of ultrasound. These films were mainly characterized by X-ray diffraction
      and low-field nuclear magnetic resonance through relaxometry, in order to obtain
      responses on the structural organization and molecular dynamic, respectively, and
      consequently to understand the effect of the nanoparticles on the EVA matrix. The
      results showed that the addition of Nb2O5 to the EVA matrix caused changes in its
      crystallinity and molecular mobility, due to the new interactions formed by the
      good dispersion of nanoparticles and also their distribution in the EVA matrix,
      changing the copolymer characteristics due to the formation of a new material.

PMID- 23862517
TI  - Synthesis of SnSe2 nanorods and nanoplates by an organic solution-phase route.
AB  - The IV-VI semiconductor nanomaterials have attracted much attention due to their
      narrow band-gap energies and most promising applications in optoelectronic
      devices. SnSe2 possesses a layered CdI2-type crystal structure and a narrow band
      gap energy of 0.97 eV, which makes it a potential candidate for photovoltaic
      applications. Two different nanomaterials that SnSe2 nanorods and nanoplates were
      synthesized simultaneously in liquid paraffin by an organic solution-phase route
      for the first time. The morphologies and growth mechanisms were studied in
      detail, and the results showed that the nanostructures grow along the (0001)
      crystal planes whether they are nanorods or nanoplates. A rational chemical
      reaction mechanism was first proposed to explain the synthesis of SnSe2. This
      letter is of importance for understanding the fundamental chemistry and physics
      for the SnSe2 nanomaterial.

PMID- 23862518
TI  - Cytotoxicity and genotoxicity induced by photothermal effects of colloidal gold
      nanorods.
AB  - Gold nanorods (Au NRs) that absorb near-infrared (NIR) light have great potential
      in the field of nanomedicine. Photothermal therapy (PTT), a very attractive
      cancer therapy in nanomedicine, combines nanomaterials and light. The aim of this
      study was to elucidate the molecular mechanism involved in Au NR-mediated
      cytotoxic, genotoxic, and other biological responses, in the presence or absence
      of NIR irradiation. Specifically, cell death mode, generation of reactive oxygen
      species, DNA damage, apoptotic gene expression, and cell morphological changes
      induced by Au NRs under NIR irradiation were evaluated in cancer cells. In human
      lung adenocarcinoma epithelial cells (A549 cells), mild necrosis via DNA damage
      was induced by NIR responsive Au NRs. Unlike in the cancer cells, cell viability
      of normal human lymphocyte was not affected by the combined treatment of Au NRs
      and NIR irradiation. This study delineates differential cytotoxic and genotoxic
      susceptibility of cancer and normal cells during photothermal treatment of Au
      NRs. In conclusion, our results suggest that the photothermal cyto-/genotoxic
      activity of Au NRs is an effective method for cancer therapy in human lung cancer
      cells.

PMID- 23862519
TI  - Scratch and abrasion properties of polyurethane-based micro- and nano-hybrid
      obturation materials.
AB  - Polyurethane-based micro- and nano-hybrid composites were produced with
      controlled porosity to be used as obturation materials. In addition to
      hydroxyapatite (HAp) micro-particles in the composites, two different ceramics
      particle types were also added: alumina micro-particles and silica nano
      particles. Particles of different sizes provide the materials with improved
      mechanical properties: the use of micro- and nano-particles produces a better
      packing because the nano-particles fill the interstitial space left by the micro
      particles, rendering an improvement in the mechanical properties. The silica and
      alumina particles provide the materials with appropriate abrasion and scratching
      properties, while the HAp provides the required bio-acceptance. The polymeric
      matrix was a mono-component solvent-free polyurethane. The porosity was selected
      by controlling the chemical reaction.

PMID- 23862520
TI  - Controlled hydrolysis synthesis and luminescence properties of uniform TiO2
      spheres with different titanium alkoxides.
AB  - A series of uniform and well-dispersed TiO2 spheres have been successfully
      synthesized through a controlled hydrolysis route by using different titanium
      alkoxides as reactants. The types of titanium alkoxides and stirring time have an
      effect on the uniformity and dispersion of the TiO2 spherical particles. The
      addition of a small amount of salt also plays a crucial role for the formation of
      the monodisperse TiO2 spheres. Under ultraviolet excitation, the as-obtained
      Eu(3+)-doped TiO2 spheres exhibit red emission corresponding to the electric
      dipole allowed 5D0-7F2 transition of Eu3+ ions, which is induced by the lack of
      inversion symmetry at the Eu3+ ions site. The Eu(3+)-doped TiO2 phosphors might
      find potential applications in the fields such as optical displays, photoelectric
      devices, and light-emitting diodes (LEDs).

PMID- 23862521
TI  - Alcohol dependent production of Fe3O4 and CoFe2O4 nanoparticles.
AB  - Commonly available alcohols of varying lengths and degree of branching were used
      to synthesize iron oxide, Fe3O4, and cobalt iron oxide, CoFe2O4, nanoparticles by
      means of a simple solvothermal decomposition of iron (III) acetylacetonates and
      cobalt (II) acetylacetonates. Depending on the solvent employed resulting Fe3O4
      and CoFe2O4 nanoparticles ranged in size from approximately 5-16 nm and
      approximately 4-8 nm, respectively. All alcohols utilized resulted in the
      formation of nanoparticles with a spinel crystal structure, with the exception of
      methanol. Use of tert-butanol and phenol resulted in nearly spherical
      agglomerations of individual nanoparticles ranging between 100-250 nm. The
      resulting structures and morphologies of all samples were confirmed by X-ray
      diffraction and electron microscopy. Mass specific moments are reported based on
      SQUID magnetometry, and ranged from 57.5(5)-76.4(3) emu/g for Fe3O4 and 47.7(7)
      67.0(4) emu/g CoFe2O4.

PMID- 23862522
TI  - Hydrophilic carbon nanoonions coated with carbon nanobubbles by laser ablation of
      carbon black suspension.
AB  - Hydrophilic carbon nanoonions coated with carbon nanobubbles were synthesized by
      long-pulse-width laser ablating of carbon black particles suspended in water. The
      high resolution TEM (HTREM), selected area electron diffraction (SAED) and Raman
      spectrometer results revealed that the crystallinity and the structure of carbon
      nanoonions. All analysis techniques showed that the hydrophilic properties of
      carbon nanoonions could be ascribed to both hydrophilic groups and carbon
      nanobubbles simultaneously formed on the surface of the synthesized carbon
      nanoonions under laser ablation, in which the carbon nanobubbles were also
      believed to improve the specific surface area and form more hydrophilic groups by
      chemical or physical absorption.

PMID- 23862523
TI  - Tone of professional article disappoints doctors.

PMID- 23862524
TI  - Where is the mutual support?

PMID- 23862525
TI  - Author's reply: To PMID 23614310.

PMID- 23862526
TI  - Enhancing PHC nurses' skills.

PMID- 23862528
TI  - New Zealand rights eroding.

PMID- 23862527
TI  - Memorial fund needs support.

PMID- 23862529
TI  - Education at Burwood Hospital.

PMID- 23862530
TI  - Company structure for health regulation.

PMID- 23862531
TI  - Health and safety report boosts workers' powers and support.

PMID- 23862532
TI  - What's affecting working nurses?

PMID- 23862533
TI  - A long, painful journey.

PMID- 23862534
TI  - Keeping older nurses working.

PMID- 23862535
TI  - Time to get off the treadmill.

PMID- 23862536
TI  - Stressed midwife's satisfaction wanes.

PMID- 23862537
TI  - Delivering good care compromised.

PMID- 23862538
TI  - Age a real advantage for Maori nurse.

PMID- 23862539
TI  - Life experience enriches practice.

PMID- 23862540
TI  - Strategies for retaining older nurses.

PMID- 23862541
TI  - Nurses keen on new prescribing roles.

PMID- 23862542
TI  - Viruses and pandemics.

PMID- 23862544
TI  - Finding the key to opening nurses' minds.

PMID- 23862543
TI  - Helping prevent the spread of pertussis.

PMID- 23862545
TI  - Lack of empathy destroys nursing's essence.

PMID- 23862546
TI  - When should nurses' names be suppressed?

PMID- 23862547
TI  - Working for a living wage.

PMID- 23862548
TI  - Cancer nursing: valuing a culture of care.

PMID- 23862549
TI  - Aged care: Equal pay case.

PMID- 23862550
TI  - Employment law: Changes by the end of the year.

PMID- 23862551
TI  - Theoretical study of H2O adsorption on Zn2GeO4 surfaces: effects of surface state
      and structure-activity relationships.
AB  - We employed the density functional theory to investigate the interaction of H2O
      with Zn2GeO4 surfaces, considering both perfect and defective surfaces. The
      results revealed that the interaction of H2O with Zn2GeO4 surfaces was dependent
      on the structure of the latter. For perfect surfaces, H2O adsorbed at the
      Ge3c...O2c site of a (010) surface could spontaneously dissociate into an H atom
      and an OH group, whereas H2O tended to adsorb at the O2c-M3c-O3c site of a (001)
      surface by molecular adsorption. The presence of oxygen defects was found to
      strongly promote H2O dissociation on the (010) surface. Analysis of the surface
      electronic structure showed a large density of Ge states at the top of the
      valence band for both perfect and defective (010) surfaces, which is an important
      factor affecting H2O dissociation. In contrast, perfect and defective (001)
      surfaces with surface Ge states buried inside the valence band were significantly
      less reactive, and H2O was adsorbed on these surfaces in the molecular form. This
      information about the adsorbate geometries, catalytic activity of various surface
      sites, specific electronic structure of surface Ge atoms, and their relevance to
      surface structure will be useful for the future design of the Zn2GeO4
      photocatalyst, as well as for the atomistic-level understanding of other
      structure-sensitive reactions. 

PMID- 23862552
TI  - 'The TIPSing Point'.

PMID- 23862556
TI  - The impact of synthetic biology.
AB  - Synthetic biology has recently been at the center of the world's attention as a
      new scientific and engineering discipline. It allows us to design and construct
      finely controllable metabolic and regulatory pathways, circuits, and networks, as
      well as create new enzymes, pathways, and even whole cells. With this great power
      of synthetic biology, we can develop new organisms that can efficiently produce
      new drugs to benefit human healthcare and superperforming microorganisms capable
      of producing chemicals, fuels, and materials from renewable biomass, without the
      use of fossil oil. Based on several successful examples reported, this commentary
      aims at peeking into the potential of synthetic biology. 

PMID- 23862557
TI  - An analysis of the impact of embryo transfer difficulty on live birth rates,
      using a standardised grading system.
AB  - BACKGROUND: Embryo transfer (ET) is a vital part of the IVF process. While some
      studies have supported the hypothesis that ET difficulty alters success rate,
      others suggest the contrary. This large population study aimed to test this
      hypothesis, using a standardised ET grading system. METHODS: ET data for fresh
      and frozen IVF/ICSI cycles between 2005 and 2010, retrieved from the IVFAustralia
      database, were grouped by degree of difficulty (easy, medium and difficult). Live
      birth rates, as the primary outcome, were compared between the groups.
      Biochemical pregnancy, Clinical Pregnancy Rate (CPR) and other pregnancy outcomes
      were assessed. The influence of blood +/- mucus contamination on the transfer
      catheter tip and the use of intra-transfer ultrasound (US) were also analysed.
      RESULTS: Of 6484 transfers, 5976 (92.2%) were considered easy, 374 (5.7%) medium
      and 134 (2.1%) difficult. Basic patient characteristics were similar between the
      cohorts. There were statistically significant differences in the live delivery
      rates (25.3% vs 19.5%, p < 0.05), CPR (30.7% vs 24.6%, p < 0.05), and + ve
      betahCG rate (35.9% vs 28%, p < 0.05) between the easy and medium/difficult
      groups. There was no significant difference in the rates of ectopic pregnancy,
      stillbirth and miscarriage between the groups. The presence of blood on the
      catheter did not affect pregnancy outcome adversely (p = ns). CONCLUSION: This
      study, which we believe to be the largest report using a standardised system for
      grading the difficulty of ET, demonstrates that difficult ETs are associated with
      lower live birth rates but not higher rates of ectopic or miscarriage. While the
      presence of blood may be an indicative of a relatively more traumatic and
      difficult transfer, it does not necessarily lead to a lower birth rate.

PMID- 23862558
TI  - Enhanced rate and selectivity by carboxylate salt as a basic cocatalyst in chiral
      N-heterocyclic carbene-catalyzed asymmetric acylation of secondary alcohols.
AB  - The rate and enantioselectivity of chiral NHC-catalyzed asymmetric acylation of
      alcohols with an adjacent H-bond donor functionality are remarkably enhanced in
      the presence of a carboxylate cocatalyst. The degree of the enhancement is
      correlated with the basicity of the carboxylate. With a cocatalyst and a newly
      developed electron-deficient chiral NHC, kinetic resolution and desymmetrization
      of cyclic diols and amino alcohols were achieved with extremely high selectivity
      (up to s = 218 and 99% ee, respectively) at a low catalyst loading (0.5 mol %).
      This asymmetric acylation is characterized by a unique preference for alcohols
      over amines, which are not converted into amides under the reaction conditions. 

PMID- 23862559
TI  - Vitamin D in rheumatoid arthritis.

PMID- 23862560
TI  - Liver abscess as a complication of laparoscopic gastric banding bariatric
      surgery.
AB  - BACKGROUND: The World Health Organization has identified the rapidly growing
      prevalence of obesity as one of today's serious health problems. Various surgical
      interventions categorized collectively as bariatric surgery now play an ever
      increasing important role as the only known effective treatment for severe
      obesity. Laparoscopic gastric bypass is currently the most frequent bariatric
      surgical procedure performed. However, the laparoscopic adjustable gastric band
      (LAGB) is rapidly gaining in popularity as a minimally invasive surgical option
      with anticipated similarly efficacious outcomes. Gastric band erosion following
      LAGB is an uncommon yet potentially serious complication unique to this form of
      weight loss surgery. METHODS: Case report and literature review. RESULTS: We
      report a case of a pyogenic liver abscess related to a LAGB procedure. Apropos to
      this case, we review the presumed pathophysiologic mechanism of this particular
      infectious process, and discuss this and other complications associated with LAGB
      operations. CONCLUSIONS: As LAGB bariatric procedures become more popular,
      clinicians need to be aware of uncommon, but potentially serious complications
      unique to this form of weight loss surgery.

PMID- 23862561
TI  - Procalcitonin as an early diagnostic marker for ventriculoperitoneal shunt
      infections.
AB  - BACKGROUND: Procalcitonin (PCT) has been considered a more reliable marker than
      others because of its specificity for bacterial infection. METHODS: Case report
      and review of the literature. RESULTS: A 50-year-old male was diagnosed with
      subarachnoid hemorrhage, intraventricular hemorrhage, and intracerebral
      hemorrhage. We performed a ruptured aneurysm clipping and left unilateral
      external ventricular drainage. We also performed ventriculoperitoneal (VP) shunt
      placement in the course; however, VP shunt infection was indicated by fever,
      increased C-reactive protein concentration and leukocytosis. The cerebrospinal
      fluid culture showed methicillin-resistant Staphylococcus epidermidis but the
      serum PCT concentration was quite low. CONCLUSIONS: Although PCT is considered a
      more reliable serological marker of bacterial meningitis in several reports, the
      serum PCT concentration did not reflect the bacterial VP shunt infection that was
      present in our case.

PMID- 23862562
TI  - Achieving day-case laparoscopic nissen fundoplication: an analysis of patient and
      operative factors.
AB  - INTRODUCTION: Day-case laparoscopic Nissen fundoplication has been described;
      however, its achievability and limitations in the setting of a busy Foundation
      Trust hospital are unclear. SUBJECTS AND METHODS: A retrospective cohort study of
      all cases undergoing laparoscopic Nissen fundoplication between January 1, 2009
      and December 31, 2010 at three hospitals in the largest and the least densely
      populated Trust in the United Kingdom was undertaken. Primary end points of
      planned and achieved day-case surgery were compared with logistic regression
      analysis. Secondary end points were unplanned re-admission and complications.
      RESULTS: During the study period 126 consecutive patients underwent laparoscopic
      Nissen fundoplication. There were 64 female patients and 62 male patients.
      Primary surgery was undertaken in 115 patients and revisional surgery in 11. The
      age range was 21-73 years. Patients had traveled up to 52.3 miles or 80.2 minutes
      for their surgery. The median length of stay was 0 days in the planned day-case
      cohort and 1 day in the inpatient cohort. Day-case surgery was planned in 85
      (68.55%). Successful day-case discharge was achieved in 71 cases (83.5%). There
      was no difference in age, geographical remoteness, surgeon volume, or length of
      surgery between planned and achieved day-case surgery. Patients were more likely
      to need unplanned admission if their American Society of Anesthesiologists grade
      was 2, when undergoing revisional surgery, and if the operation was completed
      after 1300 hours (1 p.m.). After multivariate regression analysis only operation
      completion time remained significant (P<=.05). The rate of unplanned re-admission
      related to surgery was 3/126 (2.38%). CONCLUSIONS: Day-case laparoscopic Nissen
      fundoplication can be achieved in the majority of patients. Unplanned admission
      is to be expected in approximately 15% of planned cases and cannot be predicted.

PMID- 23862563
TI  - New pathways for formation of acids and carbonyl products in low-temperature
      oxidation: the Korcek decomposition of gamma-ketohydroperoxides.
AB  - We present new reaction pathways relevant to low-temperature oxidation in gaseous
      and condensed phases. The new pathways originate from gamma-ketohydroperoxides
      (KHP), which are well-known products in low-temperature oxidation and are assumed
      to react only via homolytic O-O dissociation in existing kinetic models. Our ab
      initio calculations identify new exothermic reactions of KHP forming a cyclic
      peroxide isomer, which decomposes via novel concerted reactions into carbonyl and
      carboxylic acid products. Geometries and frequencies of all stationary points are
      obtained using the M06-2X/MG3S DFT model chemistry, and energies are refined
      using RCCSD(T)-F12a/cc-pVTZ-F12 single-point calculations. Thermal rate
      coefficients are computed using variational transition-state theory (VTST)
      calculations with multidimensional tunneling contributions based on small
      curvature tunneling (SCT). These are combined with multistructural partition
      functions (Q(MS-T)) to obtain direct dynamics multipath (MP-VTST/SCT) gas-phase
      rate coefficients. For comparison with liquid-phase measurements, solvent effects
      are included using continuum dielectric solvation models. The predicted rate
      coefficients are found to be in excellent agreement with experiment when due
      consideration is made for acid-catalyzed isomerization. This work provides
      theoretical confirmation of the 30-year-old hypothesis of Korcek and co-workers
      that KHPs are precursors to carboxylic acid formation, resolving an open problem
      in the kinetics of liquid-phase autoxidation. The significance of the new
      pathways in atmospheric chemistry, low-temperature combustion, and oxidation of
      biological lipids are discussed. 

PMID- 23862564
TI  - Multiple mechanisms in Pd(II)-catalyzed S(N)2' reactions of allylic alcohols.
AB  - Density functional calculations and experiments were used to examine mechanisms
      of Pd(II) catalyzed intramolecular cyclization and dehydration in acyclic and
      bicyclic monoallylic diols, a formal S(N)2' reaction. In contrast to the
      previously proposed syn-oxypalladation mechanism for acyclic monoallylic diols,
      calculations and experiments strongly suggest that hydrogen bonding templates a
      hydroxyl group and Pd addition across the alkene and provides a low energy
      pathway via anti-addition (anti-oxypalladation) followed by intramolecular proton
      transfer and anti-elimination of water. This anti-addition, anti-elimination
      pathway also provides a simple rationale for the observed stereospecificity. For
      bicyclic monoallylic diol compounds, Pd(II) is capable of promoting either anti-
      or syn-addition. In addition, palladium chloride ligands can mediate proton
      transfer to promote dehydration when direct intramolecular proton transfer
      between diol groups is impossible.

PMID- 23862565
TI  - Informing public health policy through deliberative public engagement: perceived
      impact on participants and citizen-government relations.
AB  - BACKGROUND: Deliberative public engagement has been proposed for policy
      development, where issues are complex and there are diverse public perspectives
      and low awareness of competing issues. Scholars suggest a range of potential
      outcomes for citizens and government agencies from involvement in such processes.
      Few studies have examined outcomes from the perspective of citizen participants
      in deliberative processes. AIMS: To examine participant perceptions of their
      involvement in and outcomes of a deliberative engagement exercise. METHOD: A case
      study using semistructured interviews was conducted with participants following a
      deliberative forum on biobanking. RESULTS: From their involvement in the
      deliberative exercise, participants described transformations in their knowledge
      and beliefs about the policy issues. They reported being more informed to the
      extent of having confidence to educate others and effectively contribute to
      public policy development. They had developed greater trust in government
      policymakers who they believed would take reasonable account of their
      recommendations. CONCLUSION: We conclude that the participants were satisfied
      with the outcomes of the deliberative public engagement process and viewed it as
      an effective means of citizen involvement in public policy development.
      Particularly for citizens who participate in deliberative processes, such
      processes may promote active citizenship, empower citizens to undertake
      representative and educative roles, and improve relations between citizens and
      government agencies. Actions taken by policymakers subsequent to the deliberative
      exercise, whereby the majority of citizen recommendations were incorporated in
      the policy developed, may have contributed to participants holding sustained
      levels of trust in the commissioning government agency.

PMID- 23862566
TI  - Watermelon juice: potential functional drink for sore muscle relief in athletes.
AB  - l-Citrulline is an excellent candidate to reduce muscle soreness, and watermelon
      is a fruit rich in this amino acid. This study investigated the potential of
      watermelon juice as a functional drink for athletes. An in vitro study of
      intestinal absorption of l-citrulline in Caco-2 cells was performed using
      unpasteurized (NW), pasteurized (80  degrees C for 40 s) watermelon juice (PW)
      and, as control, a standard of l-citrulline. l-citrulline bioavailability was
      greater when it was contained in a matrix of watermelon and when no heat
      treatment was applied. In the in vivo experiment (maximum effort test in a
      cycloergometer), seven athletes were supplied with 500 mL of natural watermelon
      juice (1.17 g of l-citrulline), enriched watermelon juice (4.83 g of l-citrulline
      plus 1.17 g from watermelon), and placebo. Both watermelon juices helped to
      reduce the recovery heart rate and muscle soreness after 24 h. 

PMID- 23862567
TI  - Polydatin: a review of pharmacology and pharmacokinetics.
AB  - CONTEXT: Polydatin, also named piceid (3,4',5-trihydroxystilbene-3-beta-d
      glucoside, PD), is a monocrystalline compound isolated from Polygonum cuspidatum
      Sieb. et Zucc. (Polygonaceae), but is also detected in grape, peanut, hop cones,
      red wines, hop pellets, cocoa-containing products, chocolate products and many
      daily diets. There are numerous investigations reported of PD in the past 22
      years, but they are usually scattered across various publications, which may
      block further research and clinical use of PD. OBJECTIVE: The article summarizes
      and evaluates the published scientific information of PD pharmacological effects
      and pharmacokinetics since 1990. MATERIALS AND METHODS: The information from 98
      cases included in this review was compiled using major databases such as MEDLINE,
      Elsevier, Springer, PubMed, Scholar and CNKI. RESULTS: Numerous pharmacological
      investigations of PD mainly focus on cardiovascular effects, neuroprotection,
      anti-inflammatory and immunoregulatory effects, anti-oxidation, anti-tumor, liver
      and lung protection, etc. CONCLUSION: A great number of pharmacological and
      pharmacokinetic investigations in the past 22 years have demonstrated that PD has
      favorable therapeutic properties, indicating its potential as an effective
      material. However, further research is needed to explore its molecular mechanisms
      of action and definitive target proteins.

PMID- 23862568
TI  - Laterality and performance of agility-trained dogs.
AB  - Correlations between lateralised behaviour and performance were investigated in
      19 agility-trained dogs (Canis familiaris) by scoring paw preference to hold a
      food object and relating it to performance during typical agility obstacles
      (jump/A-frame and weave poles). In addition, because recent behavioural studies
      reported that visual stimuli of emotional valence presented to one visual
      hemifield at a time affect visually guided motor responses in dogs, the
      possibility that the position of the owner respectively in the left and in the
      right canine visual hemifield might be associated with quality of performance
      during agility was considered. Dogs' temperament was also measured by an owner
      rated questionnaire. The most relevant finding was that agility-trained dogs
      displayed longer latencies to complete the obstacles with the owner located in
      their left visual hemifield compared to the right. Interestingly, the results
      showed that this phenomenon was significantly linked to both dogs' trainability
      and the strength of paw preference.

PMID- 23862569
TI  - Distinct geographical clustering of HIV-1 and a signature amino acid at position
      41 of the p24 unveiled by gag variability in India.
AB  - A portion of the gag gene cDNA for p24 protein from 30 Indian HIV-1 proviral DNA
      was amplified by PCR and sequenced. Phylogenetic analysis with reference samples
      of A1, A2, B, C, D, F1, F2, G, H, J, K, N and O subtypes revealed that 29 test
      samples aligned with subtype C reference strain while 1 matched with HIV-1
      subtype A. Multiple alignment of predicted amino acid sequence of the Indian test
      samples and reference C subtype of HIV-1 samples from other countries indicated a
      molecular signature by way of rigid conservation of the amino acid 'S' at
      position 41 of the gag p24 protein in all Indian HIV-1 samples analyzed in this
      study as opposed to 'T' in the same position in C subtype sequences from other
      parts of the world. A phylogenetic analysis and visualization of the resulting
      tree in radial position showed distinct clubbing of all Indian C subtypes and
      formation of a cluster when compared to C subtype sequences from other countries
      with a single Chinese sample as an exception which was found in the Indian
      cluster. The use of a portion of p24 gene sequence as tool for subtyping as well
      as phylogenetic grouping with special reference to its geographical location is
      discussed. 

PMID- 23862571
TI  - Induced abortion and breast cancer.

PMID- 23862570
TI  - The effects of repeat traumatic brain injury on the pituitary in adolescent rats.
AB  - Adolescents are one of the highest groups at risk for sustaining both traumatic
      brain injury (TBI) and repeat TBI (RTBI). Consequences of endocrine dysfunction
      following TBI have been routinely explored in adults, but studies in adolescents
      are limited, and show an incidence rate of endocrine dysfunction in 16-61% in
      patients, 1-5 years after injury. Similar to in adults, the most commonly
      affected axis is growth hormone (GH) and insulin-like growth hormone 1 (IGF-1).
      Despite TBI being the primary cause of morbidity and mortality among the
      pediatric population, there are currently no experimental studies specifically
      addressing the occurrence of pituitary dysfunction in adolescents. The present
      study investigated whether a sham, single injury or four repeat injuries (24 h
      interval) delivered to adolescent rats resulted in disruption of the GH/IGF-1
      axis. Circulating levels of basal GH and IGF-1 were measured at baseline, 24 h,
      72 h, 1 week, and 1 month after injury, and vascular permeability of the
      pituitary gland was quantified via Evans Blue dye extravasation. Changes in
      weight and length of animals were measured as a potential consequence of GH and
      IGF-1 disruption. The results from the current study demonstrate that RTBI
      results in significant acute and chronic decreases in circulation of GH and IGF
      1, reduction in weight gain and growth, and an increase in Evans Blue dye
      extravasation in the pituitary compared with sham and single injury animals. RTBI
      causes significant disruption of the GH/IGF-1 axis that may ultimately affect
      normal cognitive and physical development during adolescence.

PMID- 23862572
TI  - Assessing the permeability of the rat sciatic nerve epineural sheath against
      compounds with local anesthetic activity: an ex vivo electrophysiological study.
AB  - Abstract Studies have shown that the sciatic nerve epineural sheath acts as a
      barrier and has a delaying effect on the diffusion of local anesthetics into the
      nerve fibers and endoneurium. The purpose of this work is to assess and to
      quantify the permeability of the epineural sheath. For this purpose, we isolated
      the rat sciatic nerve in a three-chamber recording bath that allowed us to
      monitor the constant in amplitude evoked nerve compound action potential (nCAP)
      for over 24 h. For nerves exposed to the compounds under investigation, we
      estimated the IT50 the time required to inhibit the nCAP to 50% of its initial
      value. For desheathed nerves, the half-vitality time was denoted as IT50(-) and
      for the ensheath normal nerves as IT50(+). There was no significant difference
      between the IT50 of desheathed and ensheathed nerves exposed to normal saline.
      The IT50(-) for nerves exposed to 40 mM lidocaine was 12.1 +/- 0.95 s (n=14) and
      the IT50(+) was 341.4 +/- 2.49 s (n=6). The permeability (P) coefficient of the
      epineural sheath was defined as the ratio IT50(+)/IT50(-). The P coefficient for
      40 mM lidocaine and linalool was 28.2 and 3.48, correspondingly, and for 30 mM 2
      heptanone was 4.87. This is an indication that the epineural sheath provided a
      stronger barrier against lidocaine, compared to natural local anesthetics,
      linalool and 2-heptanone. The methodology presented here is a useful tool for
      studying epineural sheath permeability to compounds with local anesthetic
      properties.

PMID- 23862573
TI  - Plasma leptin and vascular endothelial growth factor (VEGF) in normal subjects at
      high altitude (5050 m).
AB  - CONTEXT: High altitude (HA) is a model of severe hypoxia exposure in humans. We
      hypothesized that nocturnal hypoxemia or acute maximal exercise at HA might
      affect plasma leptin and VEGF levels. OBJECTIVES: Plasma leptin, VEGF and other
      metabolic variables were studied after nocturnal pulse oximetry and after maximal
      exercise in healthy lowlanders on the 3rd-4th day of stay in Lobuche (5050 m, HA)
      and after return to sea level (SL). RESULTS: Leptin was similar at SL or HA in
      both pre- and post-exercise conditions. Pre-exercise VEGF at HA was lower, and
      cortisol was higher, than at SL, suggesting that nocturnal intermittent hypoxia
      associated with periodic breathing at HA might affect these variables.
      CONCLUSIONS: Leptin levels appear unaffected at HA, whereas nocturnal hypoxic
      stress may affect plasma VEGF. Future HA studies should investigate the possible
      role of nocturnal intermittent hypoxemia on metabolism.

PMID- 23862574
TI  - Elevated platelet expression of CD36 may contribute to increased risk of thrombo
      embolism in active inflammatory bowel disease.
AB  - CONTEXT: Inflammatory bowel disease (IBD) induces increased risk of thrombo
      embolism. CD36 is involved in platelet activation, glucose metabolism and
      inflammation. OBJECTIVE: The relationship between CD36 expression on platelets
      and monocytes, plasma sCD36, and CD36-positive platelet-derived microparticles
      (PDMPs) and inflammation in both active IBD and after one week of anti-tumour
      necrosis alpha antibody (anti-TNF) treatment was investigated. MATERIAL AND
      METHODS: Patients with exacerbation of Crohn's disease (n = 8) or ulcerative
      colitis (n = 5) and 13 healthy controls were enrolled. Seven patients underwent
      anti-TNF treatment for one week. Platelet, monocyte, and PDMP-CD36 were measured
      by flow-cytometry. RESULTS: Platelet CD36 expression was 34% higher in patients,
      and correlated with insulin resistance and fasting glucose. sCD36 was 37% lower
      and restored after anti-TNF treatment. CONCLUSION: Elevated platelet CD36
      expression may contribute to increased risk of thrombo-embolism in active IBD.
      This may not entirely be attributed to inflammation and secondary insulin
      resistance may play a role.

PMID- 23862575
TI  - Horizontal gene transfer in human pathogens.
AB  - Horizontal gene transfer has a tremendous impact on the genome plasticity,
      adaptation and evolution of bacteria. Horizontally transferred mobile genetic
      elements are involved in the dissemination of antibiotic resistance and virulence
      genes, thus contributing to the emergence of novel "superbugs". This review
      provides update on various mechanisms of horizontal gene transfer and examines
      how horizontal gene transfer contributes to the evolution of pathogenic bacteria.
      Special focus is paid to the role horizontal gene transfer plays in pathogenicity
      of the emerging human pathogens: hypervirulent Clostridium difficile and
      Escherichia coli (including the most recent haemolytic uraemic syndrome outbreak
      strain) and methicillin-resistant Staphylococcus aureus (MRSA), which have been
      associated with largest outbreaks of infection recently.

PMID- 23862576
TI  - A d-statistic for single-case designs that is equivalent to the usual between
      groups d-statistic.
AB  - We describe a standardised mean difference statistic (d) for single-case designs
      that is equivalent to the usual d in between-groups experiments. We show how it
      can be used to summarise treatment effects over cases within a study, to do power
      analyses in planning new studies and grant proposals, and to meta-analyse effects
      across studies of the same question. We discuss limitations of this d-statistic,
      and possible remedies to them. Even so, this d-statistic is better founded
      statistically than other effect size measures for single-case design, and unlike
      many general linear model approaches such as multilevel modelling or generalised
      additive models, it produces a standardised effect size that can be integrated
      over studies with different outcome measures. SPSS macros for both effect size
      computation and power analysis are available. 

PMID- 23862577
TI  - The lived experience of physically active older prostate cancer survivors on
      androgen deprivation therapy.
AB  - This study sought to explore the lived experiences of physically active prostate
      cancer survivors on androgen deprivation therapy (ADT), who exercise
      individually. Three older men (74-88 years old) with prostate cancer, using ADT
      continuously for at least 12 months and regularly exercising for at least 6
      months, participated in this qualitative pilot study, informed by interpretive
      phenomenology. Data were gathered using individual semi-structured interviews,
      audio recorded and transcribed verbatim. Coherent stories were drawn from each
      transcript and analyzed using iterative and interpretive methods. van Manen's
      lifeworld existentials provided a framework for interpreting across the research
      text. Three notions emerged: Getting started, Having a routine and Being with
      music. Together they reveal what drew the participants to exercising regularly
      despite the challenges associated with their cancer and treatments. This study
      provides insights into the benefits of, and what it means for, older men with
      prostate cancer to regularly exercise individually. These findings may assist
      cancer clinicians and other allied health professionals to be more attuned to
      prostate cancer survivors' lived experiences when undergoing ADT, allowing
      clinicians to better promote regular exercise to their patients as a foundational
      component of living well.

PMID- 23862578
TI  - Are the Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the
      Aging Male (ADAM) questionnaire suitable for the screening of late-onset
      hypogonadism in aging Chinese men?
AB  - The Aging Male's Symptoms (AMS) scale and the Androgen Deficiency in the Aging
      Male (ADAM) questionnaire have been widely used for screening men suspected of
      late-onset hypogonadism (LOH). We evaluated the consistency of the two
      questionnaires with sex hormone levels. A total of 985 men completed the two
      questionnaires, as well as an analysis of the serum levels of total testosterone
      (TT), bioavailable testosterone (BT), luteinizing hormone (LH), follicle
      stimulating hormone (FSH), estradiol (E2), prolactin (PRL) and sex hormone
      binding globulin (SHBG). No correlation was observed between any hormone level
      and the psychological or somatic section of the AMS score, whereas the sexual
      section was correlated with the levels of FT, LH, FSH, SHBG and BT. Significant
      correlations were observed between the result of the two questionnaires and these
      hormone levels. When LOH was defined as TT < 300 ng/dl and FT < 5 ng/dl, the
      sensitivity and specificity of the AMS scale were 54.0% and 41.2% compared with
      78.7% and 14.8% for the ADAM questionnaire. Several sex hormone levels correlated
      with the two questionnaires, but neither of these questionnaires had sufficient
      sensitivity and specificity. It is necessary to provide a new questionnaire
      applicable to the Chinese population to screening LOH.

PMID- 23862579
TI  - Tailoring the nanostructured surfaces of hydroxyapatite bioceramics to promote
      protein adsorption, osteoblast growth, and osteogenic differentiation.
AB  - To promote and understand the biological responses of the implant via
      nanostructured surface design is essential for the development of bioactive bone
      implants. However, the control of the surface topography of the bioceramics in
      nanoscale is a big challenge because of their brittle property. Herein, the
      hydroxyapatite (HAp) bioceramics with distinct nanostructured topographies were
      fabricated via hydrothermal treatment using alpha-tricalcium phosphate ceramic as
      hard-template under different reaction conditions. HAp bioceramics with
      nanosheet, nanorod and micro-nanohybrid structured surface in macroscopical size
      were obtained by controlling the composition of the reaction media. Comparing
      with the traditional sample with flat and dense surface, the fabricated HAp
      bioceramics with hierarchical 3D micro-nanotextured surfaces possessed higher
      specific surface area, which selectively enhanced adsorption of specific proteins
      including Fn and Vn in plasma, and stimulated osteoblast adhesion, growth, and
      osoteogenic differentiation. In particular, the biomimetic features of the
      hierarchical micro-nanohybrid surface resulted in the best ability for
      simultaneous enhancement of protein adsorption, osteoblast proliferation, and
      differentiation. The results suggest that the hierarchical micro-nanohybrid
      topography might be one of the critical factors to be considered in the design of
      functional bone grafts. 

PMID- 23862581
TI  - Delivering flavonoids into solid tumors using nanotechnologies.
AB  - INTRODUCTION: Long-term epidemiological studies have demonstrated that regular
      ingestion of flavonoids contained in dietary sources is associated with a reduced
      risk for many chronic diseases including cancer. However, although flavonoids are
      largely consumed in the diet and high concentrations may exist in the intestine
      after oral administration, the plasma/tissue concentrations of flavonoids are
      lower than their effective therapeutic doses due to poor bioavailability,
      resulting in the limited efficacy of flavonoids in various clinical studies.
      Therefore, the application of nanotechnology to deliver flavonoids to tumor sites
      has received considerable attention in recent years. AREAS COVERED: In this
      review, after a general review of the potential benefits of flavonoids in cancer
      therapy and several key factors affecting their bioavailability, the current
      efforts in improving the delivery efficacy of promising candidates that are
      particularly important in the human diet, namely quercetin, epigallocatechin-3
      gallate (EGCG) and genistein were focused on. Finally, the challenges of
      developing flavonoid delivery systems that improve flavonoid bioavailability and
      their anticancer therapy potentials were summarized. EXPERT OPINION: The design
      of suitable molecular carriers for flavonoids is an area of research that is in
      rapid progress. A large number of unheeded promising favonoids are suffering from
      poor in vivo parameters, their potential benefits deserves further research.
      Furthermore, more effort should be placed on developing active targeting systems,
      evaluating the efficacy and toxicity of novel flavonoid delivery systems through
      small and large scale clinical trials.

PMID- 23862582
TI  - Predictive factors for pregnancy during the first four intrauterine insemination
      cycles using gonadotropin.
AB  - PURPOSE: Although a variety of factors have been reported as affecting pregnancy
      rates after intrauterine insemination (IUI), there have been conflicting results
      on prognostic factors. This study aimed to determine predictive factors for
      pregnancy in patients undergoing the first four IUI cycles. METHODS: A total of
      348 IUI cycles using clomiphene citrate or letrozole combined with gonadotropin,
      or gonadotropin only were analyzed. Baseline clinical characteristics, variables
      related to ovulation induction and sperm parameters were compared between
      pregnant (n = 54) and non-pregnant groups (n = 294). Logistic regression analysis
      was performed to identify factors that could predict a pregnancy. RESULTS: The
      overall clinical pregnancy rate was 15.5% (54/348) per cycle and 30.0% (54/180)
      per couple. During the first four IUI cycles, logistic regression analysis
      revealed that woman who were 39 years or older (OR: 0.263, 95% CI: 0.076-0.906, p
      = 0.034), longer duration of infertility (OR: 0.967, 95% CI: 0.942-0.993, p =
      0.012), endometriosis (versus unexplained infertility; OR: 0.177, 95% CI: 0.040
      0.775, p = 0.022) and endometrial thickness below 7 mm (OR: 0.114, 95% CI: 0.015
      0.862, p = 0.035) were unfavorable factors to predict clinical pregnancy.
      CONCLUSIONS: Women with old age, longer duration of infertility, the presence of
      endometriosis or thin endometrium in the preovulatory phase may have unfavorable
      outcomes during the first four IUI cycles.

PMID- 23862583
TI  - Putative association between UBE2E2 polymorphisms and the risk of gestational
      diabetes mellitus.
AB  - We hypothesized that ubiquitin-conjugating enzyme E2 E2 (UBE2E2) may be
      associated with gestational diabetes mellitus (GDM) and conducted association
      analyses. A total of 2071 subjects were recruited for the study, with 1104 cases
      and 967 controls. Two UBE2E2 single-nucleotide polymorphisms rs6780569 and
      rs7612463, and their haplotypes were analyzed for the study. As a result,
      rs7612463 showed a significant association with GDM in the recessive model. In
      addition, the regression analyses for the phenotypes showed that rs6780569.
      rs7612463 and ht2 showed significant associations with fasting plasma glucose
      (FPG) in recessive models, while ht1 showed an association in the dominant model.
      Our results show that the genetic variants of UBE2E2 are associated with GDM and
      FPG, which could be an important preliminary result for future studies.

PMID- 23862584
TI  - The effects of estrogen and progesterone on blood glutamate levels during normal
      pregnancy in women.
AB  - The purpose of this study was to examine whether changes in estrogen and
      progesterone levels observed during normal pregnancy influence blood glutamate
      levels. One-hundred and sixteen pregnant women were divided into three groups
      based on gestational age: group 1 included women in their first trimester, group
      2 included women in their second trimester, and group 3 included women in their
      third trimester. A single venous blood sample was collected and analyzed for
      concentrations of estrogen, progesterone, glutamate-pyruvate transaminase (GPT),
      glutamate-oxaloacetate transaminase (GOT), and glutamate. Concentrations of blood
      glutamate were significantly lower during the second trimester (p < 0.001) and
      third trimester (p < 0.001). Blood glutamate levels were inversely correlated
      with levels of estrogen and progesterone throughout pregnancy (p < 0.001). Levels
      of GOT and GPT remained stable during the course of pregnancy, apart from a
      moderate reduction in GPT during the third trimester. Increases in estrogen and
      progesterone levels during advanced stages of pregnancy were inversely correlated
      with maternal blood glutamate concentrations. Once a maximal blood glutamate
      reducing effect was achieved, any additional estrogen and progesterone had a
      negligible effect on blood glutamate. This study demonstrates the glutamate
      reducing effects of estrogen and progesterone, which is most likely not mediated
      by a GOT/GPT conversion mechanism.

PMID- 23862586
TI  - Comparison of macroscopic one-layer over number 1 nylon suture vasovasostomy with
      the standard two-layer microsurgical procedure.
AB  - OBJECTIVE: To compare the outcomes of macroscopic one-layer vasovasostomy (MOLVV)
      with those of two-layer microsurgical vasovasostomy (TLMVV). METHODS: Standard
      TLMVV was performed in 112 men (Group 1), while MOLVV was performed in 94
      patients. All of the MOLVVs were performed with number 1 nylon suture as a
      temporary stent. The outcome measures were as follows: patency rate, pregnancy
      rate, operation time, total procedure cost, and complications. RESULTS: The mean
      operation duration was 114 +/- 10 min for the TLMVV technique, and 74 +/- 5 min
      for the MOLVV procedure (P = 0.024). In patients who underwent vasal patency at 6
      month postoperative period, the median sperm density (106/mL) was 28.3 and 27.7
      in Groups 1 and 2, respectively (P = 0.62). At the same time, the median total
      motile sperm count (* 106) was 39.4 and 32.6 in two-layer microsurgical and one
      layer macroscopic groups, respectively (P = 0.47). Patency rates were 82.1% in
      Group 1 and 77.7% in Group 2, which were not significantly different (P = 0.21).
      The pregnancy rate was 28.4% for patients in Group 1 and 26.7% for patients in
      Group 2 (P = 0.38). CONCLUSIONS: There were no significant differences in terms
      of patency and pregnancy rates between MOLVV and TLMVV methods, but the MOLVV
      technique offers a decreased cost and operative time, and a simplified procedure.

PMID- 23862587
TI  - 2*2 dominant achievement goal profiles in high-level swimmers.
AB  - The goal of this study was to assess achievement goal dominance, self-determined
      situational motivation and competence in high-level swimmers before and after
      three training sessions set at different working intensities (medium, sub-maximal
      and maximal). Nineteen athletes (males, n=9, 18.00+/-2.32 years; females, n=10,
      16.30+/-2.01 years, range = 14-18) agreed to participate. They completed a
      questionnaire that included the Dominant Achievement Goal assessment instrument,
      the 2*2 Achievement Goals Questionnaire for Sport (AGQ-S), The Situational
      Motivation Scale (SIMS) and the Competence subscale of the Basic Psychological
      Needs in Exercise questionnaire (BPNES). Results indicated that participants
      overwhelmingly showed mastery-approach achievement goal dominance, and it
      remained stable at the conclusion of the different training sessions under all
      intensity levels. This profile was positively correlated to self-determined
      situational motivation and competence. However, swimmers' feelings of competence
      increased only after the medium intensity level training session. After the
      completion of the maximal intensity training session, swimmers' self-determined
      motivation was significantly lower compared to the other two training sessions,
      which could be caused by a temporary period of burnout. Results indicated that
      high-level swimmers had a distinct mastery-approach dominant achievement goal
      profile that was not affected by the workload of the different training sessions.
      They also showed high levels of self-determined situational motivation and
      competence. However, heavy workloads should be controlled because they can cause
      transitory burnout.

PMID- 23862585
TI  - Comparison of bevacizumab and cabergoline in the treatment of ovarian
      hyperstimulation syndrome in a rat model.
AB  - The aim of this study is to investigate the effects of bevacizumab in a rat model
      of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline. The
      study was performed with 24 rats in four main groups (one non-stimulated control
      and three OHSS treatment groups; bevacizumab, cabergoline and placebo). The rats
      were randomly assigned to four experimental groups (six rats per group). Efficacy
      of treatment was assessed on 29th day by measuring weight gain, number of eggs,
      presence of ascites and ovarian weight. Peritoneal fluid levels of vascular
      endothelial growth factor (VEGF) were measured using an enzyme-linked
      immunosorbent assay. Ovarian weights were significantly higher in the OHSS groups
      than the control group. Ovarian weights in OHSS placebo group were found to be
      higher than those in OHSS-treatment groups (p = 0.002). VEGF levels were found
      increased in the OHSS-placebo group compared with the control group (p < 0.05).
      This increase was not seen in the OHSS groups treated with either bevacizumab or
      cabergoline. We demonstrate in this study that bevacizumab can lower VEGF
      production and ovarian weight in rats treated with gonadotropins.

PMID- 23862588
TI  - Protective effects of equol and their polyphenolic isomers against dermal aging:
      microarray/protein evidence with clinical implications and unique delivery into
      human skin.
AB  - CONTEXT: Equol is a polyphenolic/isoflavonoid molecule that can be expressed as
      isomers. However, the characteristics of the equol isomers on dermal gene/protein
      expression and human skin percutaneous absorption remain unknown. OBJECTIVE:
      Perform a comprehensive investigation on equol as: R-equol, racemic equol or S
      equol to determine their differential expression of skin-related genes, quantify
      collagen expression and determine percutaneous absorption in human skin. METHODS:
      Quantified: (i) gene expression/mRNA levels via gene array technology using human
      skin equivalents with equol exposure at 1.2% in qPCR experiments, (ii) in vitro
      collagen expression in human fibroblasts, and (iii) percutaneous absorption by
      Franz cell techniques. RESULTS: In the qPCR studies, only three genes displayed
      the greatest significant expression by S-equol, whereas 16 genes displayed the
      greatest significant levels (either stimulation or inhibition) by R-equol and/or
      racemic equol, such as extracellular matrix proteins (i.e., collagen and
      elastin), nerve growth factor, aging genes [FOS, 100 A8 and A9 calcium-binding
      proteins, 5alpha-reductase type 1, and matrix metalloproteinases (1, 3, and 9)],
      and inflammatory genes (e.g., interleukin-1 alpha, interleukin-6, and
      cyclooxygenase-1). Collagen type I expression in fibroblasts was greater with
      racemic versus S-equol treatment at 1 and 10 nM. Percutaneous absorption
      demonstrated high sequestering in keratinocytes with subsequent
      accumulation/release over time. DISCUSSION AND CONCLUSION: Overall, these results
      illustrate the significant differences in mirror-image molecules or isomers of
      equol where R-equol and/or racemic equol are better molecules for skin gene
      expression compared to S-equol and the percutaneous absorption of equol
      represents a unique epidermal reservoir delivery mechanism.

PMID- 23862589
TI  - Global aging and the allocation of health care across the life span.

PMID- 23862590
TI  - Justice between age groups: an objection to the prudential lifespan approach.
AB  - Societal aging raises challenging ethical questions regarding the just
      distribution of health care between young and old. This article considers a
      proposal for age-based rationing of health care, which is based on the prudential
      life span account of justice between age groups. While important objections have
      been raised against the prudential life span account, it continues to dominate
      scholarly debates. This article introduces a new objection, one that develops out
      of the well-established disability critique of social contract theories. I show
      the implications of this critique for the prudential life span account and for
      the special case of age-group justice. The result is that age-based rationing
      based on the prudential life span approach is not supported, and that the
      prudential life span approach itself is not the best way to think about
      allocating health care between age groups. I propose an alternative approach that
      avoids the disability objection, and consider its implications for specific
      proposals for age-based rationing of health care. 

PMID- 23862591
TI  - Professional responsibility to and for patients and the ethics of health policy.

PMID- 23862592
TI  - Whose dignity, which capacity?

PMID- 23862593
TI  - From normal species functioning to capabilities, is it enough?

PMID- 23862594
TI  - Why Jecker's capabilities approach to age-based rationing is incapable of
      containing health care costs.

PMID- 23862595
TI  - Should human dignity be upheld at all costs?

PMID- 23862596
TI  - In defense of the PLA.

PMID- 23862597
TI  - Under the veil.

PMID- 23862598
TI  - Treating patients as persons: a capabilities approach to support delivery of
      person-centered care.
AB  - Health services internationally struggle to ensure health care is "person
      centered" (or similar). In part, this is because there are many interpretations
      of "person-centered care" (and near synonyms), some of which seem unrealistic for
      some patients or situations and obscure the intrinsic value of patients'
      experiences of health care delivery. The general concern behind calls for person
      centered care is an ethical one: Patients should be "treated as persons." We made
      novel use of insights from the capabilities approach to characterize person
      centered care as care that recognizes and cultivates the capabilities associated
      with the concept of persons. This characterization unifies key features from
      previous characterisations and can render person-centered care applicable to
      diverse patients and situations. By tying person-centered care to intrinsically
      valuable capability outcomes, it incorporates a requirement for responsiveness to
      individuals and explains why person-centered care is required independently of
      any contribution it may make to health gain. 

PMID- 23862599
TI  - A better grounding for person-centered medicine?

PMID- 23862600
TI  - The ambiguity of personhood.

PMID- 23862601
TI  - Can person-centered care deal with atypical persons?

PMID- 23862602
TI  - The contribution of the capabilities approach to reconciling culturally competent
      care and nondiscrimination.

PMID- 23862603
TI  - Capabilities and patients as persons: ethical implications for health economics.

PMID- 23862604
TI  - The person at the center.

PMID- 23862605
TI  - A capabilities perspective on healthcare associated infection.

PMID- 23862606
TI  - Disabling the patient by incorporating the capabilities approach into person
      centered care.

PMID- 23862607
TI  - Bringing a critical structural frame to person-centered care.

PMID- 23862608
TI  - Person-centered care, autonomy, and the definition of health.

PMID- 23862609
TI  - Person-centered health care: capabilities and identity.

PMID- 23862610
TI  - More required on the patient role and standardization.

PMID- 23862611
TI  - A capabilities approach to person-centered care: response to open peer
      commentaries on "Treating patients as persons: a capabilities approach to support
      delivery of person-centered care".

PMID- 23862613
TI  - Clinical relevance of diagnosing COPD by fixed ratio or lower limit of normal: a
      systematic review.
AB  - BACKGROUND: Different spirometric criteria in diagnosing COPD have been advocated
      by different groups, debilitating adequate diagnosis and treatment of COPD. We
      reviewed the clinical relevance of fixed ratio and lower limit of normal (LLN) in
      diagnosing COPD and explored if modifying factors may affect their clinical
      relevance. METHODS: Two reviewers independently searched PubMed and Embase for
      papers that compared both criteria on any clinically relevant outcome, published
      before June 1st, 2012, without any language restriction. Two reviewers
      independently extracted the study characteristics, including study design,
      population characteristics and diagnostic criteria used, and summarized the
      results of clinical relevance. Study quality was assessed by scoring forms for
      bias and level of evidence. RESULTS: Of 394 studies retrieved, 11 studies were
      included, with a median of 1,258 participants. Although both criteria appeared
      related with various clinically relevant outcomes, we were unable to prefer one
      criterion over the other, with various performances of the criteria for different
      outcomes. Should the criteria disagree on diagnosis, an alternative diagnosis
      should be suspected, in particular in those (elderly) with less severe airflow
      limitation for whom the LLN appears a better criterion. The fixed ratio appears
      to perform better in subjects with more severe airflow limitation. CONCLUSION: In
      diagnosing COPD, severity of airflow limitation appears an important factor for
      choosing whether the fixed ratio or LLN. Disagreement between the criteria is
      suggestive for an alternative diagnosis. Future studies on clinical relevance
      should further reveal the criterion of choice, in order to improve adequate
      diagnosis and consequent treatments.

PMID- 23862612
TI  - Development of second generation gold-supported palladium material with low
      leaching and recyclable characteristics in aromatic amination.
AB  - An improved process for the preparation of sulfur-modified gold-supported
      palladium material [SAPd, second generation] is presented. The developed
      preparation method is safer and generates less heat (aqueous Na2S2O8 and H2SO4)
      for sulfur fixation on a gold surface, and it is superior to the previous method
      of preparing SAPd (first generation), which requires the use of the more heat
      generating and dangerous piranha solution (concentrated H2SO4 and 35% H2O2) in
      the sulfur fixation step. This safer and improved preparation method is
      particularly important for the mass production of SAPd (second generation) for
      which the catalytic activity was examined in ligand-free Buchwald-Hartwig cross
      coupling reactions. The catalytic activities were the same between the first and
      second generation SAPds in aromatic aminations, but the lower palladium leaching
      properties and safer preparative method of second generation SAPd are a
      significant improvement over the first generation SAPd. 

PMID- 23862614
TI  - Intrathecal magnetic drug targeting using gold-coated magnetite nanoparticles in
      a human spine model.
AB  - AIM: We aimed to magnetically guide and locally confine nanoparticles in desired
      locations within the spinal canal to achieve effective drug administration for
      improved treatment of chronic pain, cancers, anesthesia and spasticity. MATERIALS
      & METHODS: We developed a physiologically and anatomically consistent in vitro
      human spine model to test the feasibility of intrathecal magnetic drug targeting.
      Gold-coated magnetite nanoparticles were infused into the model and targeted to
      specific regions using external magnetic fields. Experiments and simulations
      aiming to determine the effect of key parameters, such as magnet strength,
      duration of magnetic field exposure, magnet location and ferrous implants, on the
      collection efficiency of superparamagnetic nanoparticles in targeted regions were
      performed. RESULTS: An 891% increase in nanoparticle collection efficiency within
      the target region was achieved using intrathecal magnetic drug targeting when
      compared with the control. Nanoparticle collection efficiency at the target
      region increased with time and reached a steady value within 15 min. Ferrous
      epidural implants generated sufficiently high-gradient magnetic fields, even when
      magnets were placed at a distance equal to the space between a patient's
      epidermis and spinal canal. CONCLUSION: Our experiments indicate that intrathecal
      magnetic drug targeting is a promising technique for concentrating and localizing
      drugs at targeted sites within the spinal canal for treating diseases affecting
      the CNS.

PMID- 23862615
TI  - The new compound GET73, N-[(4-trifluoromethyl)benzyl]4-methoxybutyramide,
      Regulates hippocampal Aminoacidergic transmission possibly via an allosteric
      modulation of mGlu5 receptor. Behavioural evidence of its "anti-alcohol" and
      anxiolytic properties.
AB  - The present article attempts to provide, on the basis of data emerging from
      studies carried out in our laboratories, a summary of the chemical and
      pharmacological properties of the new compound N-[(4-trifluoromethyl)benzyl]4-
      methoxybutyramide (GET73). Particular emphasis is given to findings obtained in
      vivo and in vitro suggesting that an allosteric modulation of metabotropic
      glutamate receptor 5 (mGlu5 receptor) by GET73 may represent the mechanism
      underlying the effects of the compound produced on rat hippocampal glutamate and
      GABA transmission. Furthermore, behavioural findings demonstrating how this new
      compound reduces alcohol intake, displays anxiolytic properties, and influences
      spatial memory in rats are also summarized. Since mGlu5 receptors play an
      important role in regulating several central actions of drugs of abuse, and the
      hippocampus is a crucial brain area involved in addiction, anxiety, and spatial
      memory, a possible link between mGlu5 receptor allosteric modulation and the
      profiles of action of GET73 is proposed, although to date no studies have yet
      explored GET73 binding at the mGlu5 receptor orthosteric and/or allosteric sites.
      Following a brief overview of glutamatergic neurotransmission, mGlu receptor
      structures and activation mechanisms, the general properties of mGlu5 receptor
      and its allosteric modulators are described in the first part of the review. 

PMID- 23862616
TI  - The role of transcription factors in the formation of an arrhythmogenic substrate
      in congestive human heart failure.
AB  - Human congestive heart failure is accompanied by structural and electrical
      alterations leading to the development of an arrhythmogenic substrate. This
      substrate is associated with the "sudden cardiac death" due to ventricular
      tachycardia or ventricular fibrillation. Multiple studies link distinct
      transcription factors to the transcriptional regulation of genes related to the
      formation of an arrhythmogenic substrate. In addition to cardiac hypertrophy the
      up- or downregulation of ion channels, calcium-handling proteins, and proteins
      forming gap junctions play a pivotal role in the progression of heart failure.
      This review summarizes the transcriptional regulation of selected genes
      implicated in the formation of an arrhythmogenic substrate. In this context we
      provide an overview of relevant transcription factors, activating stimuli and
      pathways, the evidence of binding to respective elements in the promoter of
      target genes and the associated mRNA regulation in animal models. Finally,
      possible therapeutic consequences are discussed. 

PMID- 23862617
TI  - Tuberculosis clinical trial update and the current anti-tuberculosis drug
      portfolio.
AB  - Tuberculosis (TB), an ongoing public health threat, is worsened by the emergence
      of drug resistance. With an estimated 630000 cases per year of multidrug
      resistant (MDR)-TB, and 9% of those being extensively drug resistant (XDR)-TB,
      there is an urgent need for new and more effective anti-TB drugs. New TB
      treatment regimens should be able to shorten the duration of therapy that
      currently takes at least six months. The non-compliance with this long treatment
      duration is one of the reasons for the development of drug resistance. In spite
      of the difficulties and alleged lack of interest from the pharmaceutical industry
      for the discovery and development of new antibiotics, several new or repurposed
      drugs are being evaluated in clinical trials. This review article summarizes the
      information available and presents an update on the drugs currently in clinical
      trials for TB and briefly introduces some new compounds in pre-clinical
      development. 

PMID- 23862618
TI  - Medicinal chemistry of quinolines as emerging anti-inflammatory agents: an
      overview.
AB  - Quinoline-based small molecules have been explored and being developed as anti
      inflammatory agents targeting several pharmacological targets namely
      Phosphodiesterase 4 (PDE4), Transient Receptor Potential Vanilloid 1 (TRPV1), TNF
      alpha converting enzyme (TACE) and Cyclooxygenase (COX). Efforts on Structure
      Activity Relationship (SAR) studies revealed that the pharmacological activities
      and target specificities of these quinoline derivatives were mainly dependent on
      the nature and position of substituent(s) present on the quinoline ring. For
      example, quinolines having carboxamide moiety displayed TRPV1 antagonism whereas
      that with carboxylic acid showed COX-inhibition. Similarly, quinolines possessing
      aniline moiety at C-4, aryl group at C-8 and oxazole ring at C-5 showed PDE4
      inhibition. These quinoline derivatives were synthesized by using various
      synthetic approaches like Pd-mediated C-C (e.g. Suzuki, Sonogashira type coupling
      etc.) or C-N (the Buchwald-Hartwig type coupling) or C-S bond formation, AlCl3
      induced C-C bond formation, traditional amide bond formation or amination,
      formation of ether linkage or additional heterocyclic rings. All these efforts
      resulted in the discovery of several quinoline-based anti-inflammatory agents for
      the potential treatment of acute as well as chronic inflammatory diseases.

PMID- 23862619
TI  - Experimental antiarrhythmic targets: CaMKII inhibition - ready for clinical
      evaluation?
AB  - In the recent years, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was
      suggested to be associated with cardiac hypertrophy and heart failure but also
      with arrhythmias both in animal models as well as in the human heart. This
      article focuses on the role of CaMKII for excitation-contraction coupling but
      more explicitly it highlights major CaMKIIdependent proarrhythmogenic mechanisms
      including SR Ca(2+) leak and late Na(+) current. Because a clinical significance
      of CaMKII is implied for both mechanisms, CaMKII inhibition is suggested to be a
      therapeutical approach in the near future. 

PMID- 23862620
TI  - Free fatty acids-sensing G protein-coupled receptors in drug targeting and
      therapeutics.
AB  - G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain
      receptor) superfamily represents the largest protein family in the human genome.
      These receptors respond to various physiological ligands such as photons, odors,
      pheromones, hormones, ions, and small molecules including amines, amino acids to
      large peptides and steroids. Thus, GPCRs are involved in many diseases and the
      target of around half of all conventional drugs. The physiological roles of free
      fatty acids (FFAs), in particular, long-chain FFAs, are important for the
      development of many metabolic disease including obesity, diabetes, and
      atherosclerosis. In the past half decade, deorphanization of several GPCRs has
      revealed that GPR40, GPR41, GPR43, GPR84 and GPR120 sense concentration of
      extracellular FFAs with various carbon chain lengths. GPR40 and GPR120 are
      activated by medium- and long-chain FFAs. GPR84 is activated by medium- chain,
      but not long-chain, FFAs. GPR41 and GPR43 are activated by short-chain FFAs.
      GPR40 is highly expressed in pancreatic beta cells and plays a crucial role in
      FFAs-induced insulin secretion. GPR120 is mainly expressed in enteroendocrine
      cells and plays an important role for FFAs-induced glucagon-like peptide-1. GPR43
      is abundant in leukocytes and adipose tissue, whilst GPR41 is highly expressed in
      adipose tissue, the pancreas and leukocytes. GPR84 is expressed in leukocytes and
      monocyte/macrophage. This review aims to shed light on the physiological roles
      and development of drugs targeting these receptors. 

PMID- 23862621
TI  - Endocrine disruptor agent nonyl phenol exerts an estrogen-like transcriptional
      activity on estrogen receptor positive breast cancer cells.
AB  - Several substances widely dispersed in the environment including hormones,
      industrial by-products and pollutants exert hormone like activity affecting
      steroid-responsive physiological systems. These compounds, named endocrine
      disruptors, are suspected to affect the mammalian reproductive system. However it
      is still unclear whether these substances are able to elicit estrogen like
      activity at the low concentrations encountered in the environment. Here we
      compare the effects of the endocrine disruptor nonylphenol with the effects
      elicited by 17-beta-estradiol on gene transcription in the human breast cancer
      cell line MCF7. The correlation of the nonylphenol induced gene expression
      alterations with a reference profile of estradiol treated cells shows that
      nonylphenol at a concentration of 100 nM exerts a significant effect on estrogen
      responsive gene transcription in MCF7 cells. Most of the genes regulated by 17
      beta-estradiol respond to the nonylphenol in the same direction though to a much
      lesser extent. Molecular modeling of the potential interaction of nonylphenol
      with the estrogen receptor alpha shows that nonylphenol is likely to bind to the
      estrogen receptor alpha. 

PMID- 23862622
TI  - Reactive oxygen species in cancer biology and anticancer therapy.
AB  - Reactive oxygen species (ROS) are a group of highly reactive chemicals under
      tight control of intracellular antioxidants. The balance in oxidation
      antioxidation is essential for maintaining normal cell functions, and any
      imbalance could lead to a wide range of diseases including cancer. The
      intracellular level of ROS is generally elevated in cancer cells, revealing a
      critical role of ROS in the process of carcinogenesis and cancer progression.
      Conversely, there is also evidence showing that ROS can act as cancer
      suppressors. This may be due to the varying antioxidant capacities of different
      cancers. These findings indicate a complex redox state in cancer cells. In this
      review we summarize the main features of ROS and their functions with respect to
      cancer initiation, hallmarks of cancer, and signaling in cancer cells. ROS
      elevating and ROS-depleting anticancer strategies and their mechanisms are
      thoroughly discussed. We argue that the rationale for therapy choice depends on a
      complete understanding of cancer cell redox state, namely, the "redox signaling
      signature" of cancer.

PMID- 23862623
TI  - Effects of nanoscale confinement on the functionality of nucleic acids:
      implications for nanomedicine.
AB  - The facile self-assembly and nanomanipulation of nucleic acids hold great promise
      in the design of innovative, programmable materials, with applications ranging
      from biosensing to cellular targeting and drug delivery. Little is known,
      however, of the effects of confinement on biochemical reactions within such
      systems, in which the level of packing and crowding is similar to that of
      intracellular environments. In this review article we outline novel, unexpected
      properties of nucleic acids that arise from nanoscale confinement, as mainly
      revealed by atomic force and electron microscopy, electrochemistry, fluorescence
      spectroscopy, and gel electrophoresis. We review selected scientific studies over
      the last decade that describe the novel behavior of nanoconfined nucleic acids
      with respect to hybridization, denaturation, conformation, stability, and enzyme
      accessibility. The nanoscale systems discussed include self-assembled, water
      soluble, DNA or RNA nanostructures, ranging in width from a few to several tens
      of nm; gold nanoparticles coated with DNA monolayers; and self-assembled
      monolayers of DNA, from a few to several hundreds of bp in length. These studies
      reveal that the functionality of nucleic acid-based nanosystems is highly
      dependent upon the local density, molecular flexibility and network of weak
      interactions between adjacent molecules. These factors significantly affect
      steric hindrance, molecular crowding and hydration, which in turn control nucleic
      acid hybridization, denaturation, conformation, and enzyme accessibility. The
      findings discussed in this review article demonstrate that nucleic acids function
      in a qualitatively different manner within nanostructured systems, and suggest
      that these novel properties, if better understood, will enable the development of
      powerful molecular tools for nanomedicine. 

PMID- 23862624
TI  - Discovery and characterization of an isopeptidase that linearizes lasso peptides.
AB  - Lasso peptides are a class of ribosomally derived natural products with diverse
      bioactivities. The characteristic threaded lasso structure in these peptides
      derives from an isopeptide bond attaching the N-terminus of the peptide to an
      acidic side chain. Here we describe the heterologous expression of a lasso
      peptide gene cluster encoding two lasso peptides, astexin-2 and astexin-3, and
      solve the solution structure of astexin-3. This cluster also encodes an enzyme
      annotated as a protease. We show that this enzyme, AtxE2, is a lasso peptide
      isopeptidase that specifically hydrolyzes astexins-2 and -3, converting them to
      linear peptides. Astexin-3 is highly thermostable and resists unthreading after
      extensive heat treatment. In contrast, astexin-2 unthreads upon heat treatment.
      AtxE2 has no activity toward unthreaded astexin-2, demonstrating that this
      isopeptidase must recognize a knotted structure in order to function. We also use
      this isopeptidase as a tool to study evolutionary relationships between lasso
      peptide gene clusters. 

PMID- 23862625
TI  - Feasibility of using drinking water treatment residuals as a novel chlorpyrifos
      adsorbent.
AB  - Recent efforts have increasingly focused on the development of low-cost
      adsorbents for pesticide retention. In this work, the novel reuse of drinking
      water treatment residuals (WTRs), a nonhazardous ubiquitous byproduct, as an
      adsorbent for chlorpyrifos was investigated. Results showed that the kinetics and
      isothermal processes of chlorpyrifos sorption to WTRs were better described by a
      pseudo-second-order model and by the Freundlich equation, respectively. Moreover,
      compared with paddy soil and other documented absorbents, the WTRs exhibited a
      greater affinity for chlorpyrifos (log Koc = 4.76-4.90) and a higher chlorpyrifos
      sorption capacity (KF = 5967 mg(1-n).L.kg(-1)) owing to the character and high
      content of organic matter. Further investigation demonstrated that the pH had a
      slight but statistically insignificant effect on chlorpyrifos sorption to WTRs;
      solution ionic strength and the presence of low molecular weight organic acids
      both resulted in concentration-dependent inhibition effects. Overall, these
      results confirmed the feasibility of using WTRs as a novel chlorpyrifos
      adsorbent. 

PMID- 23862626
TI  - Reaction pathway and free energy profile for papain-catalyzed hydrolysis of N
      acetyl-Phe-Gly 4-nitroanilide.
AB  - Possible reaction pathways for papain-catalyzed hydrolysis of N-acetyl-Phe-Gly 4
      nitroanilide (APGNA) have been studied by performing pseudobond first-principles
      quantum mechanical/molecular mechanical-free energy (QM/MM-FE) calculations. The
      whole hydrolysis process includes two stages: acylation and deacylation. For the
      acylation stage of the catalytic reaction, we have explored three possible paths
      (A, B, and C) and the corresponding free energy profiles along the reaction
      coordinates. It has been demonstrated that the most favorable reaction path in
      this stage is path B consisting of two reaction steps: the first step is a proton
      transfer to form a zwitterionic form (i.e., Cys-S-/His-H+ ion-pair), and the
      second step is the nucleophilic attack on the carboxyl carbon of the substrate
      accompanied by the dissociation of 4-nitroanilide. The deacylation stage includes
      the nucleophilic attack of a water molecule on the carboxyl carbon of the
      substrate and dissociation between the carboxyl carbon of the substrate and the
      sulfhydryl sulfur of Cys25 side chain. The free energy barriers calculated for
      the acylation and deacylation stages are 20.0 and 10.7 kcal/mol, respectively.
      Thus, the acylation is rate-limiting. The overall free energy barrier calculated
      for papain-catalyzed hydrolysis of APGNA is 20.0 kcal/mol, which is reasonably
      close to the experimentally derived activation free energy of 17.9 kcal/mol.

PMID- 23862627
TI  - Total synthesis of (+)-trienomycins A and F via C-C bond-forming hydrogenation
      and transfer hydrogenation.
AB  - The triene-containing C17-benzene ansamycins trienomycins A and F were prepared
      in 16 steps (longest linear sequence, LLS) and 28 total steps. The C11-C13
      stereotriad was generated via enantioselective Ru-catalyzed alcohol CH syn
      crotylation followed by chelation-controlled carbonyl dienylation.
      Enantioselective Rh-catalyzed acetylene-aldehyde reductive coupling mediated by
      gaseous H2 was used to form a diene that ultimately was subjected to diene-diene
      ring closing metathesis to form the macrocycle. The present approach is 14 steps
      shorter (LLS) than the prior syntheses of trienomycins A and F, and 8 steps
      shorter than any prior synthesis of a triene-containing C17-benzene ansamycin. 

PMID- 23862628
TI  - Stomata actively regulate internal aeration of the sacred lotus Nelumbo nucifera.
AB  - The sacred lotus Nelumbo nucifera (Gaertn.) possesses a complex system of gas
      canals that channel pressurized air from its leaves, down through its petioles
      and rhizomes, before venting this air back to the atmosphere through large
      stomata found in the centre of every lotus leaf. These central plate stomata
      (CPS) lie over a gas canal junction that connects with two-thirds of the gas
      canals within the leaf blade and with the larger of two discrete pairs of gas
      canals within the petiole that join with those in the rhizome. It is hypothesized
      that the lotus actively regulates the pressure, direction and rate of airflow
      within its gas canals by opening and closing these stomata. Impression casting
      the CPS reveal that they are open in the morning, close at midday and reopen in
      the afternoon. The periodic closure of the CPS during the day coincides with a
      temporary reversal in airflow direction within the petiolar gas canals.
      Experiments show that the conductance of the CPS decreases in response to
      increasing light level. This behaviour ventilates the rhizome and possibly
      directs benthic CO2 towards photosynthesis in the leaves. These results
      demonstrate a novel function for stomata: the active regulation of convective
      airflow. 

PMID- 23862629
TI  - Hierarchical mesoporous silica nanofibers as multifunctional scaffolds for bone
      tissue regeneration.
AB  - Mesoporous materials with pore sizes between 2 and 50 nm have elicited widespread
      interest in catalysis, separation, adsorption, sensors, and drug delivery
      applications due to its highly ordered pore size along with high hydrothermal
      stability and easily modifiable surface functionalities. Fabricating these
      mesoporous materials as continuous fibers offers exciting vistas for biomedical
      applications especially in tissue engineering. The aim of the present study was
      to fabricate, characterize, and evaluate the cellular and gene expression of
      mesoporous silica with a long ordered fibrous morphology to support regeneration
      of bone tissue. Tetraethyl orthosilicate, polyvinyl pyrrolidone, and the tri
      block copolymer P-123 were subjected to electrospinning to fabricate continuous
      ordered mesoporous silica nanofibers by optimizing solution and operation
      parameters. Mesoporous silica fibers with an average diameter of 470 nm and
      mesopores of dimension 5.97 nm were obtained. The combination of micropores,
      mesopores, macropores, and the nanofibrous morphology imparted excellent
      bioactivity to the mesoporous silica fibrous scaffolds as demonstrated by the
      proliferation of human osteoblast-like cells (MG63) and by the maintenance of its
      phenotype. The upregulation of collagen I, alkaline phosphatase, osteocalcin,
      osteopontin, and bone sialoprotein signifies the maturation of MG63 cells on the
      silica scaffold. Hence, these novel scaffolds are promising new biomaterials for
      orthopaedic applications.

PMID- 23862630
TI  - Agreeing to disagree: deaf and hearing children's awareness of subject-verb
      number agreement.
AB  - This study investigated deaf adolescents' implicit and explicit awareness of
      subject-verb number agreement. In Experiment 1, a self-paced reading task, the
      reading times of deaf and hearing children (matched for reading and chronological
      age, mean=8;3 and 13;10 years) increased when sentences contained disagreeing
      subject-verb number markers. However, deaf adolescents' slowing occurred later in
      the sentence than it did in both groups of hearing children. The same deaf
      adolescents were unable to detect and correct subject-verb agreement errors in
      Experiment 2, whereas both groups of hearing children performed well on this
      task. Thus, deaf adolescents demonstrated implicit awareness of agreement in the
      absence of explicit knowledge. Moreover, this nascent awareness was below that
      expected on the basis of their (substantially delayed) reading ability.
      Therefore, grammatical difficulties could be a significant impediment to deaf
      children's literacy. Future research should examine whether this is a result of
      late or incomplete learning of English, bilingualism, or another factor.

PMID- 23862631
TI  - Modeling clinical endpoints as a function of time of switch to second-line ART
      with incomplete data on switching times.
AB  - Modeling clinical endpoints as a function of change in antiretroviral therapy
      (ART) attempts to answer one simple but very challenging question: was the change
      in ART beneficial or not? We conceive a similar scientific question of interest
      in the current manuscript except that we are interested in modeling the time of
      ART regimen change rather than a comparison of two or more ART regimens. The
      answer to this scientific riddle is unknown and has been difficult to address
      clinically. Naturally, ART regimen change is left to a participant and his or her
      provider and so the date of change depends on participant characteristics. There
      exists a vast literature on how to address potential confounding and those
      techniques are vital to the success of the method here. A more substantial
      challenge is devising a systematic modeling strategy to overcome the missing time
      of regimen change for those participants who do not switch to second-line ART
      within the study period even after failing the initial ART. In this article, we
      adopt and apply a statistical method that was originally proposed for modeling
      infusion trial data, where infusion length may be informatively censored, and
      argue that the same strategy may be employed here. Our application of this method
      to therapeutic HIV/AIDS studies is new and interesting. Using data from the AIDS
      Clinical Trials Group (ACTG) Study A5095, we model immunological endpoints as a
      polynomial function of a participant's switching time to second-line ART for 182
      participants who already failed the initial ART. In our analysis, we find that
      participants who switch early have somewhat better sustained suppression of HIV-1
      RNA after virological failure than those who switch later. However, we also found
      that participants who switched very late, possibly censored due to the end of the
      study, had good HIV-1 RNA suppression, on average. We believe our scientific
      conclusions contribute to the relevant HIV literature and hope that the basic
      modeling strategy outlined here would be useful to others contemplating similar
      analyses with partially missing treatment length data. 

PMID- 23862632
TI  - Tuning gold nanoparticles interfaces by specific peptide interaction for surface
      enhanced Raman spectroscopy (SERS) and separation applications.
AB  - Surface functionalization and control over nanostructured interfaces represents a
      key aspect in nanoscience and nanobiotechnology. Nanoplasmonic structures for
      analyte detection typically require sophisticated nanofabrication techniques, as
      well as bioactivated nanostructures that need multistep conjugations for chemical
      ligation. An alternative to such complex processes is to rely on specific
      biomolecules adsorption for decoration or self-assembly of nanoparticles at
      solid/liquid interface. In principle, small biomolecules with specific binding
      properties to nanostructures could control the assembly without modifying the
      nanoparticle chemistry, pH of the solution or salt concentration. Importantly,
      such an approach could be direct, robust, and reversible. In this work, we report
      about the use of a specific peptide for direct and reversible adsorption on gold
      nanoparticles with tuned interfacial properties just by simply adjusting the
      ratio between the numbers of peptide molecules to the number of gold
      nanoparticles. This easy, direct and reversible assembly of gold nanoparticles
      mediated by the specific peptide makes this platform ideal for small-volume
      samples and low concentrations detection using surface enhanced Raman
      Spectroscopy, as well as for the capture or separation of biomolecules in complex
      mix. 

PMID- 23862633
TI  - The development of mismatch responses to Mandarin lexical tones in early infancy.
AB  - This study examined how maturation and the size of deviance affect the
      development of mismatch responses to Mandarin lexical tones by a multi-deviant
      oddball paradigm with both large deviant T1/T3 and small deviant T2/T3 pairs in
      newborns and 6-month-olds. The T1/T3 pair elicited a positive mismatch response
      (P-MMR) at birth but an adult-like mismatch negativity (MMN) at 6 months of age.
      For the T2/T3 pair, no significant MMR was seen in newborns, whereas a P-MMR was
      found when infants are 6 months old. Results suggest that the developmental
      trajectories of MMRs are dependent on the neural maturation and the
      discriminability of tonal changes. 

PMID- 23862634
TI  - The neural development of response inhibition in 5- and 6-year-old preschoolers:
      an ERP and EEG study.
AB  - Many studies have used event-related potential and neural oscillations to probe
      the underlying neural mechanisms of inhibitory control in adults, but little has
      been done in typically developing preschoolers. In this study we tested healthy
      preschool children between the ages of 5 and 6, and observed better response
      inhibition in 6-year-olds compared to 5-year-olds. Importantly, this age-related
      difference could not be explained by the N2 component from event-related
      potential, but was reflected in an increase in right frontal beta power from
      electroencephalogram. These results suggest that frontal beta power during the
      preschool period may reflect neural development of inhibitory control. 

PMID- 23862636
TI  - Neural substrates for heightened anxiety in children with brain tumors.
AB  - This study investigated anxiety symptoms' associations with cognitive functioning
      and tumor locus in pediatric brain tumor patients. Data from 91 patients were
      collected as part of a neuropsychological assessment. Significant relationships
      were found between anxiety symptoms and mental set shifting (Wisconsin Card
      Sorting). Analyses revealed patients with right cortical tumors or left
      cerebellar tumors had significantly greater anxiety than those with
      midline/bilateral tumor and those with left cortical or right cerebellar tumors.
      Results support the specific risk of anxiety with right cortical and left
      cerebellar tumors. Results highlight the association of anxiety and one important
      element of executive functioning. 

PMID- 23862635
TI  - A one-hour sleep restriction impacts brain processing in young children across
      tasks: evidence from event-related potentials.
AB  - The effect of mild sleep restriction on cognitive functioning in young children
      is unclear, yet sleep loss may impact children's abilities to attend to tasks
      with high processing demands. In a preliminary investigation, six children (6.6
      8.3 years of age) with normal sleep patterns performed three tasks: attention
      ("Oddball"), speech perception (consonant-vowel syllables), and executive
      function (Directional Stroop). Event-related potentials (ERPs) responses were
      recorded before (Control) and following 1 week of 1-hour per day of sleep
      restriction. Brain activity across all tasks following Sleep Restriction differed
      from activity during Control Sleep, indicating that minor sleep restriction
      impacts children's neurocognitive functioning. 

PMID- 23862637
TI  - The N170 to angry faces predicts anxiety in typically developing children over a
      two-year period.
AB  - Enhanced threat processing has been associated with elevated anxiety in adults,
      but less is known about how threat processing influences the developmental
      trajectory of anxiety in children. We used the N170 to measure threat (angry
      faces) processing in relation to child anxiety over a 2-year period. Participants
      were 27 typically developing 5-to-7-year-olds (13 females). Higher anxiety when
      children were aged 5 to 7 was associated with higher anxiety 2 years later, but
      only for children showing larger N170 amplitudes to angry versus happy faces. The
      N170 captures individual differences in threat processing that may characterize
      children at enhanced risk for anxiety. 

PMID- 23862638
TI  - Editorial comment for Kadlec et al.

PMID- 23862639
TI  - Emergence of New Delhi metallo-beta-lactamase 1 (NDM-1) producing and multidrug
      resistant uropathogens causing urinary tract infections in Andaman Islands,
      India.
AB  - The present study was undertaken to understand the distribution and the
      antimicrobial susceptibility patterns of the uropathogens in the remote islands
      of India. Patients' demographical data, urine culture results, and resistance
      rates were analyzed and multidrug resistant isolates were characterized.
      Significant bacteriuria was found in 16 (17.7%, 95% confidence interval [CI] 8.47
      23.53%) samples, which includes Escherichia coli 9 (56.3%); Klebsiella pneumoniae
      3 (18.8%); Enterobacter sp. 2 (12.5%) and Proteus mirabilis 2 (12.5%). The
      uropathogens showed a wide resistance involving 3-21 drugs with 15 different
      resistance patterns. Among the 16 isolates, 13 (81.3%, 95% CI 62.13-100.37%) and
      11 (68.8%, 95% CI 46.04-91.46%) isolates were resistant to fluoroquinolones and
      third generation cephalosporins, respectively. Multiple mutations were detected
      in quinolone resistance determining region (QRDR) of the fluoroquinolone
      resistant isolates and all third generation cephalosporin resistant isolates
      producing extended-spectrum beta-lactamase. A total of 7 (44%, 95% CI 17.02
      70.98%) isolates was found to harbor plasmid mediated quinolone resistance
      determinants The present study reports for the first time the presence of the New
      Delhi metallo-beta-lactamase (NDM-1) gene in two isolates of P. mirabilis in
      these islands. Detection of multidrug resistant and NDM-1 producing isolates from
      cases of urinary tract infection in these remote islands lends support to the
      belief that the existence of these highly resistant strains is perhaps more
      widespread than previously thought and underscores the need for immediate
      implementation of antibiotic policy integrated with a continuous surveillance
      system. The study strengthens the need for a continuous surveillance system of
      antibiotic resistance in these remote Islands.

PMID- 23862640
TI  - Knowledge, attitudes, and practices associated with menopause: a multi-ethnic,
      qualitative study in Singapore.
AB  - We explored knowledge, attitudes, and practices associated with the menopause
      transition particular to women in the multi-ethnic cultural context of Singapore.
      Fifty-eight Chinese, Malay, and Indian Singaporean women participated in
      interviews that were audiorecorded, transcribed verbatim, and analyzed using
      thematic analysis. Women from all three ethnicities described an attitude of
      acceptance surrounding menopause and the changes associated with it. While they
      thought it was important to be informed, they did not seek out information about
      menopause and did not view health professionals as useful sources of information.
      Management practices were diverse and rarely involved accessing health
      professionals. 

PMID- 23862641
TI  - Thickness-dependent interfacial Coulomb scattering in atomically thin field
      effect transistors.
AB  - Two-dimensional semiconductors are structurally ideal channel materials for the
      ultimate atomic electronics after silicon era. A long-standing puzzle is the low
      carrier mobility (MU) in them as compared with corresponding bulk structures,
      which constitutes the main hurdle for realizing high-performance devices. To
      address this issue, we perform a combined experimental and theoretical study on
      atomically thin MoS2 field effect transistors with varying the number of MoS2
      layers (NLs). Experimentally, an intimate MU-NL relation is observed with a 10
      fold degradation in MU for extremely thinned monolayer channels. To accurately
      describe the carrier scattering process and shed light on the origin of the
      thinning-induced mobility degradation, a generalized Coulomb scattering model is
      developed with strictly considering device configurative conditions, that is,
      asymmetric dielectric environments and lopsided carrier distribution. We reveal
      that the carrier scattering from interfacial Coulomb impurities (e.g., chemical
      residues, gaseous adsorbates, and surface dangling bonds) is greatly intensified
      in extremely thinned channels, resulting from shortened interaction distance
      between impurities and carriers. Such a pronounced factor may surpass lattice
      phonons and serve as dominant scatterers. This understanding offers new insight
      into the thickness induced scattering intensity, highlights the critical role of
      surface quality in electrical transport, and would lead to rational performance
      improvement strategies for future atomic electronics. 

PMID- 23862642
TI  - Double proton transfer induced twisted intramolecular charge transfer emission in
      2-(4'-N,N-dimethylaminophenyl)imidazo[4,5-b]pyridine.
AB  - The spectral characteristics of N,N-dimethyl-4-(4-methyl-4H-imidazo[4,5-b]pyridin
      2-yl)benzenamine (PyN-Me), 1-methyl-2-(4'-(N,N-dimethylaminophenyl)imidazo[4,5
      b]pyridine (ImNH-Me), and 2-phenylimidazo[4,5-b]pyridine (PIP) are investigated
      to understand the mechanism of protic solvent induced dual fluorescence of 2-(4'
      N,N-dimethylaminophenyl)imidazo[4,5-b]pyridine (DMAPIP-b). No dual emission is
      observed from PyN-Me where pyridyl nitrogen blocked from hydrogen bonding with
      protic solvents confirms the importance of hydrogen bonding of protic solvents
      with the pyridyl nitrogen in dual emission of DMAPIP-b. Like DMAPIP-b, ImNH-Me
      also exhibits weak emission and has a shorter fluorescence lifetime in methanol.
      However, single emission is observed from ImNH-Me in all solvents including
      protic solvents. This suggests that the imidazole >NH hydrogen also plays a role
      in the dual emission process. The longer wavelength emission of DMAPIP-b in water
      increases with increase in pH of the solution owing to deprotonation of the
      imidazole >NH group. On the basis of these results, the mechanism for the dual
      emission of DMAPIP-b is proposed. 

PMID- 23862643
TI  - Brainwave entrainment for better sleep and post-sleep state of young elite soccer
      players - a pilot study.
AB  - The effect of sleep deprivation on psychophysical performance and well-being is
      comprehensively investigated. Research investigating the effect of improved sleep
      is rare. Just as little exists about attempts to support athletic mental state
      and performance by improving sleep quality. This study aims to investigate
      whether sleep quality of top athletes can be improved by auditory brainwave
      entrainment and whether this leads to enhancements of post-sleep psychophysical
      states. In a pilot study, 15 young elite soccer players were stimulated for eight
      weeks during sleep with binaural beats around 2-8 Hz. Once a week after wake-up,
      participants completed three different questionnaires: a sleep diary, an
      adjective list for psychophysical and motivational state, and a self-assessment
      questionnaire for sleep and awakening quality. Fifteen sport students executed
      the same protocol sleeping on the same pillow, but without stimulation.
      Subjective ratings of sleep and awakening quality, sleepiness and motivational
      state were significantly improved only in the intervention group, but did not
      impact their perceived physical state. In summary, eight weeks of auditory
      stimulation with binaural beats improved perceived sleep quality and the post
      sleep state of athletes, whereas the effect on physical level is assumed to occur
      in a time-delayed fashion. It seems to be worthwhile - to further elaborate long
      time effects and consequences on physical and mental performance.

PMID- 23862644
TI  - Omega-3 fatty acids, hepatic lipid metabolism, and nonalcoholic fatty liver
      disease.
AB  - Long-chain omega-3 fatty acids belong to a family of polyunsaturated fatty acids
      that are known to have important beneficial effects on metabolism and
      inflammation. Such effects may confer a benefit in specific chronic
      noncommunicable diseases that are becoming very prevalent in Westernized
      societies [e.g., nonalcoholic fatty liver disease (NAFLD)]. Typically, with a
      Westernized diet, long-chain omega-6 fatty acid consumption is markedly greater
      than omega-3 fatty acid consumption. The potential consequences of an alteration
      in the ratio of omega-6 to omega-3 fatty acid consumption are increased
      production of proinflammatory arachidonic acid-derived eicosanoids and impaired
      regulation of hepatic and adipose function, predisposing to NAFLD. NAFLD
      represents a spectrum of liver fat-related conditions that originates with
      ectopic fat accumulation in liver (hepatic steatosis) and progresses, with the
      development of hepatic inflammation and fibrosis, to nonalcoholic steatohepatitis
      (NASH). If the adipose tissue is inflamed with widespread macrophage
      infiltration, the production of adipokines may act to exacerbate liver
      inflammation and NASH. Omega-3 fatty acid treatment may have beneficial effects
      in regulating hepatic lipid metabolism, adipose tissue function, and
      inflammation. Recent studies testing the effects of omega-3 fatty acids in NAFLD
      are showing promise and suggesting that these fatty acids may be useful in the
      treatment of NAFLD. To date, further research is needed in NAFLD to (a) establish
      the dose of long-chain omega-3 fatty acids as a treatment, (b) determine the
      duration of therapy, and (c) test whether there is benefit on the different
      component features of NAFLD (hepatic fat, inflammation, and fibrosis). 

PMID- 23862645
TI  - Evolutionary perspectives on the obesity epidemic: adaptive, maladaptive, and
      neutral viewpoints.
AB  - The prevalence of obesity in modern societies has two major contributory factors
      an environmental change that has happened in historical times and a genetic
      predisposition that has its origins in our evolutionary history. Understanding
      both aspects is complex. From an evolutionary perspective, three different types
      of explanation have been proposed. The first is that obesity was once adaptive
      and enabled us to survive (or sustain fecundity) through periods of famine.
      People carrying so-called thrifty genes that enabled the efficient storage of
      energy as fat between famines would be at a selective advantage. In the modern
      world, however, people who have inherited these genes deposit fat in preparation
      for a famine that never comes, and the result is widespread obesity. The key
      problem with this, and any other adaptive scenario, is to understand why, if
      obesity was historically so advantageous, many people did not inherit these
      thrifty genes and in modern society are able to remain slim, despite the
      environmental change favoring fat storage. The second type of explanation is that
      obesity is not adaptive and may never even have existed in our evolutionary past,
      but it is favored today as a maladaptive by-product of positive selection on some
      other trait. An example of this type of explanation is the suggestion that
      obesity results from variation in brown adipose tissue thermogenesis. Finally, a
      third class of explanation is that most mutations in the genes that predispose us
      to obesity are neutral and have been drifting over evolutionary time--so-called
      drifty genes, leading some individuals to be obesity prone and others obesity
      resistant. In this article, I review the current evidence for and against these
      three different scenarios and conclude that the thrifty gene hypothesis is
      untenable but the other two ideas may provide a cogent explanation of the modern
      obesity phenomenon.

PMID- 23862646
TI  - Human preimplantation embryo development in vitro: a morphological assessment of
      sibling zygotes cultured in a single medium or in sequential media.
AB  - A comparison was made of the development of human zygotes in either a one-step
      (Global(r) medium) or two-step culture system (Quinn's Advantage(r)). A total of
      257 normally fertilized 2PN zygotes from 28 patients were used in the study. The
      study was broken down into two parts: the first concerned the development of
      embryos from Days 1 to 3 in Global(r) medium and Quinn's Advantage(r) cleavage
      medium; the second consisted of a comparison of the development of embryos from
      Day 3 to 5/6 in Global(r) medium and Quinn's Advantage(r) blastocyst medium.
      There were no significant differences between the two culture media with respect
      to embryo quality throughout the preimplantation phase of human embryo
      development as determined by the extent and variability of the cell counts,
      fragmentation, and nucleation. A difference was noted in the blastomere symmetry
      of Day 2 embryos in the two media, but was no longer apparent on examination of
      Day 3 embryos. No differences were noted in the rates of blastocyst development,
      inner cell mass (ICM), and trophectoderm (TE) scores in the two culture media.
      Finally, no significant differences were noted with either the proportion of
      blastocysts chosen for transfer or cryopreservation (vitrification). The findings
      support the view that two-step sequential media protocols are sufficient but not
      necessary to support the complete in vitro development of human preimplantation
      embryos.

PMID- 23862647
TI  - Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous
      infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: a
      multicenter, randomized, double-blind, crossover study (SPARK).
AB  - Augmentation therapy with the approved dose of 60 mg/kg weekly intravenous (IV)
      alpha-1 proteinase inhibitor (alpha1-PI), achieves a trough serum level of 11 MUM
      in individuals with alpha-1 antitrypsin deficiency (AATD), yet this is still
      below the level observed in healthy individuals. This study assessed the safety
      and pharmacokinetic profile of weekly infusions of a 120 mg/kg dose of alpha1-PI
      in 30 adults with AATD. Subjects with symptomatic, genetically determined
      (genotypes PI*ZZ, PI*Z(null), PI*(null)(null) or PI*(Z)Mmalton) AATD were
      randomly assigned to weekly infusions of 60 or 120 mg/kg alpha1-PI (Prolastin
      C(r)) for 8 weeks before crossing over to the alternate dose for 8 weeks. Adverse
      events (AEs) (including exacerbations), vital signs, pulmonary function tests,
      and laboratory assessments were recorded. Pharmacokinetic measurements included
      AUC0-7days, Cmax, trough, tmax, and t1/2, based on serum alpha1-PI
      concentrations. In total for both treatments, 112 AEs were reported, with
      exacerbation of COPD being the most frequent, consistent with the subjects'
      diagnoses. Mean steady-state serum alpha1-PI concentrations following 120 mg/kg
      weekly IV alpha1-PI were higher than with the 60 mg/kg dose and mean trough
      concentrations were 27.7 versus 17.3 MUM, respectively. Dose proportionality was
      demonstrated for AUC0-7days and Cmax, with low inter-subject variability. The 120
      mg/kg alpha1-PI weekly dose was considered to be safe and well tolerated, and
      provided more favorable physiologic alpha1-PI serum levels than the currently
      recommended 60 mg/kg dose. The effect of this dosing regimen on slowing and/or
      preventing emphysema progression in subjects with AATD warrants further
      investigation.

PMID- 23862648
TI  - Antioxidant and anti-cholinesterase activity of Sargassum wightii.
AB  - CONTEXT: Sargassum has been used in traditional Chinese medicine since the eighth
      century AD to treat goiter. Sargassum wightii Greville (Sargassaceae) is a major
      source of alginic acid used widely in food and drug industries. OBJECTIVE: To
      evaluate the anti-Alzheimer potential of S. wightii through evaluation of
      antioxidant and cholinesterase inhibitory activities. MATERIALS AND METHODS:
      Successive extraction was done using solvents of varying polarity. Solvent
      extracts (100-500 ug/mL) were employed for all the antioxidant assays. Free
      radical scavenging activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl, OH*,
      H2O2 radical scavenging assay. The reducing power of the seaweed was evaluated by
      ferric reducing antioxidant power and reducing power assay. Cholinesterase (ChE)
      inhibitory activity was evaluated and the Km, Vmax and Ki were calculated.
      Further, compound characterization was done by GC-MS analysis. RESULTS: The non
      polar extracts were found to possess significant antioxidant activity. At 100
      MUg/mL, petroleum ether, hexane, benzene and dichloromethane extracts showed
      significant ChE inhibitory activity with IC50 values of 19.33 +/- 0.56, 46.81 +/-
      1.62, 27.24 +/- 0.90, 50.56 +/- 0.90 ug/mL, respectively, for AChE, and 17.91 +/-
      0.65, 32.75 +/- 1.00, 12.98 +/- 0.31, 36.16 +/- 0.64 ug/mL, respectively, for
      BuChE. GC-MS reveals that 1,2-benzenedicarboxylic acid, diisooctyl ester is the
      major compound present in dichloromethane extract of S. wightii. The mode of
      inhibition exhibited by dichloromethane extract against the cholinesterases was
      found to be competitive type. DISCUSSION AND CONCLUSION: The presence of high
      amount of terpenoids could be the possible reason for its potential antioxidant
      and ChE inhibitory activity.

PMID- 23862650
TI  - Free radical coupling of o-semiquinones uncovered.
AB  - As a rule, o-semiquinones decay through disproportionation leading to equimolar
      amounts of catechol and o-quinone products. However, the o-semiquinone 1S
      generated by pulse radiolysis oxidation of the eumelanin precursor 5,6
      dihydroxyindole (1) decays with second-order kinetics to generate broad visible
      chromophores that are incompatible with the predicted absorption of 5,6
      indolequinone (1Q). Using an integrated chemical, pulse radiolytic and
      computational approach as well as deuterium labeling, we show herein that 1S and
      related 5,6-dihydroxyindole semiquinones decay mainly by a free radical coupling
      mechanism. This conclusion was supported by the inverse kinetic isotope effect
      observed with deuterated 1S, the identification of unprecedented dihydrobiindole
      products by one-electron oxidation of 1, the good matching of simulated
      absorption profiles of free radical coupling products of 1S with experimental
      spectra, and a detailed computational analysis of the kinetics and thermodynamics
      of the disproportionation equilibrium and free radical coupling of 1S versus 1-1Q
      coupling. These results disclose, to the best of our knowledge, the first example
      of free radical dimerization of o-semiquinones outcompeting the classic
      disproportionation-driven catechol-quinone coupling and suggest that this
      hitherto unrecognized process may be of broader relevance than previously
      believed. 

PMID- 23862649
TI  - A proteomics strategy for the identification of FAT10-modified sites by mass
      spectrometry.
AB  - The ubiquitin-like protein FAT10 (HLA-F adjacent transcript 10) is uniquely
      expressed in mammals. The fat10 gene is encoded in the MHC class I locus in the
      human genome and is related to some specific processes, such as apoptosis, immune
      response, and cancer. However, biological knowledge of FAT10 is limited, owing to
      the lack of identification of its conjugates. FAT10 covalently modifies proteins
      in eukaryotes, but only a few substrates of FAT10 have been reported until now,
      and no FATylated sites have been identified. Here, we report the proteome-scale
      identification of FATylated proteins by liquid chromatography coupled with tandem
      mass spectrometry (LC-MS/MS). We identified 175 proteins with high confidence as
      FATylated candidates. A total of 13 modified sites were identified for the first
      time by a modified search of the raw MS data. The modified sites were highly
      enriched with hydrophilic amino acids. Furthermore, the FATylation processes of
      hnRNP C2, PCNA, and PDIA3 were verified by a coimmunoprecipitation assay. We
      confirmed that most of the substrates were covalently attached to a FAT10
      monomer. The functional distribution of the FAT10 targets suggests that FAT10
      participates in various biological processes, such as translation, protein
      folding, RNA processing, and macromolecular complex assembly. These results
      should be very useful for investigating the biological functions of FAT10. 

PMID- 23862651
TI  - Disseminated histoplasmosis diagnosed by peripheral blood film in a patient with
      chronic lymphocytic leukaemia.

PMID- 23862652
TI  - Influence of drug encapsulation within mixed micelles on the excited state
      dynamics and accessibility to ionic quenchers.
AB  - Photophysical techniques, specifically time-resolved fluorescence and laser flash
      photolysis, have proven to be noninvasive, straightforward, and valuable tools to
      demonstrate how drug encapsulation into biomimetic mixed micelles (MM) influences
      the dynamics of excited states and their accessibility to ionic quenchers. This
      concept has been illustrated by choosing a set of currently administered drugs
      containing a common naphthalene chromophore, namely, (S)-naproxen and its methyl
      ester, (R)-cinacalcet and (S)-propranolol. A remarkable increase of their triplet
      lifetimes is noticed when experiments are performed in MM, indicating efficient
      entrapment of the drugs in these supramolecular entities. Furthermore, a decrease
      of 1 order of magnitude in the quenching rate constant of the singlet and triplet
      excited states (by iodide or nitrite, respectively) is observed upon
      encapsulation into MM. This approach can in principle be extended to other
      microenvironments capable of incorporating photoactive compounds. 

PMID- 23862653
TI  - Phytogenic biosynthesis and emission of methyl acetate.
AB  - Acetylation of plant metabolites fundamentally changes their volatility,
      solubility and activity as semiochemicals. Here we present a new technique termed
      dynamic (13) C-pulse chasing to track the fate of C1-3 carbon atoms of pyruvate
      into the biosynthesis and emission of methyl acetate (MA) and CO2 . (13) C
      labelling of MA and CO2 branch emissions respond within minutes to changes in
      (13) C-positionally labelled pyruvate solutions fed through the transpiration
      stream. Strong (13) C-labelling of MA emissions occurred only under pyruvate-2
      (13) C and pyruvate-2,3-(13) C feeding, but not pyruvate-1-(13) C feeding. In
      contrast, strong (13) CO2 emissions were only observed under pyruvate-1-(13) C
      feeding. These results demonstrate that MA (and other volatile and non-volatile
      metabolites) derive from the C2,3 atoms of pyruvate while the C1 atom undergoes
      decarboxylation. The latter is a non-mitochondrial source of CO2 in the light
      generally not considered in studies of CO2 sources and sinks. Within a tropical
      rainforest mesocosm, we also observed atmospheric concentrations of MA up to 0.6
      ppbv that tracked light and temperature conditions. Moreover, signals partially
      attributed to MA were observed in ambient air within and above a tropical
      rainforest in the Amazon. Our study highlights the potential importance of acetyl
      coenzyme A (CoA) biosynthesis as a source of acetate esters and CO2 to the
      atmosphere. 

PMID- 23862654
TI  - Clinical, economic and humanistic burdens of skeletal-related events associated
      with bone metastases.
AB  - Despite effective skeletal-related event (SRE)-limiting therapies such as
      zoledronic acid and denosumab, SREs continue to place a meaningful burden on
      patients, providers and payers. However, studies of SRE-related effects on
      clinical (i.e., survival), economic (i.e., cost per event) and humanistic (i.e.,
      quality of life) outcomes often report results in a composite manner and
      frequently do not differentiate the effects by SRE-type (i.e., bone radiation,
      bone surgery, hypercalcemia, pathological fracture and spinal cord compression).
      Nevertheless, understanding the differential burdens of individual SRE types,
      which vary in severity and duration of effect, is an important consideration -
      particularly in pharmacoeconomic evaluations of SRE-limiting therapies. In this
      review of the clinical, economic and humanistic SRE burden, it was found that SRE
      types can be differentiated by these outcomes, although economic outcomes are far
      more frequently reported than clinical or humanistic. 

PMID- 23862655
TI  - The reliability, minimal detectable change and concurrent validity of a gravity
      based bubble inclinometer and iphone application for measuring standing lumbar
      lordosis.
AB  - PURPOSE: To investigate the reliability, minimal detectable change (MDC90) and
      concurrent validity of a gravity-based bubble inclinometer (inclinometer) and
      iPhone(r) application for measuring standing lumbar lordosis. METHODS: Two
      investigators used both an inclinometer and an iPhone(r) with an inclinometer
      application to measure lumbar lordosis of 30 asymptomatic participants. RESULTS:
      ICC models 3,k and 2,k were used for the intrarater and interrater analysis,
      respectively. Good interrater and intrarater reliability was present for the
      inclinometer with Intraclass Correlation Coefficients (ICC) of 0.90 and 0.85,
      respectively and the iPhone(r) application with ICC values of 0.96 and 0.81. The
      minimal detectable change (MDC90) indicates that a change greater than or equal
      to 7 degrees  and 6 degrees  is needed to exceed the threshold of error using the
      iPhone(r) and inclinometer, respectively. The concurrent validity between the two
      instruments was good with a Pearson product-moment coefficient of correlation (r)
      of 0.86 for both raters. Ninety-five percent limits of agreement identified
      differences ranging from 9 degrees  greater in regards to the iPhone(r) to 8
      degrees  less regarding the inclinometer. CONCLUSION: Both the inclinometer and
      iPhone(r) application possess good interrater reliability, intrarater reliability
      and concurrent validity for measuring standing lumbar lordosis. This
      investigation provides preliminary evidence to suggest that smart phone
      applications may offer clinical utility comparable to inclinometry for
      quantifying standing lumbar lordosis. Clinicians should recognize potential
      individual differences when using these devices interchangeably.

PMID- 23862656
TI  - Quantification of amygdalin in nonbitter, semibitter, and bitter almonds (Prunus
      dulcis) by UHPLC-(ESI)QqQ MS/MS.
AB  - Amygdalin is a cynaogenic diglucoside responsible for the bitterness of almonds.
      Almonds display three flavor phenotypes, nonbitter, semibitter, and bitter.
      Herein, the amygdalin content of 20 varieties of nonbitter, semibitter, and
      bitter almonds from four primary growing regions of California was determined
      using solid-phase extraction and ultrahigh-pressure liquid chromatography
      electrospray triple-quadrupole mass spectrometry (UHPLC-(ESI)QqQ MS/MS). The
      detection limit for this method is <= 0.1 ng/mL (3 times the signal-to-noise
      ratio) and the LOQ is 0.33 ng/mL (10 times the signal-to-noise ratio), allowing
      for the reliable quantitation of trace levels of amygdalin in nonbitter almonds
      (0.13 mg/kg almond). Results indicate that amygdalin concentrations for the three
      flavor phenotypes were significantly different (p < 0.001). The mean
      concentrations of amygdalin in nonbitter, semibitter, and bitter almonds are
      63.13 +/- 57.54, 992.24 +/- 513.04, and 40060.34 +/- 7855.26 mg/kg, respectively.
      Levels of amygdalin ranged from 2.16 to 157.44 mg/kg in nonbitter, from 523.50 to
      1772.75 mg/kg in semibitter, and from 33006.60 to 53998.30 mg/kg in bitter
      almonds. These results suggest that phenotype classification may be achieved on
      the basis of amygdalin levels. Growing region had a statistically significant
      effect on the amygdalin concentration in commercial varieties (p < 0.05).

PMID- 23862658
TI  - Psychometric properties and factorial structure of the Spence Children's Anxiety
      Scale (SCAS) in Spanish adolescents.
AB  - The Spence Children's Anxiety Scale is an instrument widely applied in the
      assessment of the most common anxiety disorders in children and adolescents. This
      study examines its psychometric properties and the factorial structure in a large
      community sample of Spanish-speaking adolescents (N = 1,374) aged 13 to 17 years.
      The scale demonstrated strong internal consistency and good convergent and
      discriminant validity. Factor analysis confirmed the 6-factor original model,
      providing a good fit of the data for the Spanish sample. The good psychometric
      properties support its use by clinicians and researchers, adding evidence to the
      international empirical support for this measure.

PMID- 23862657
TI  - Working conditions, health and productivity among dentists in Swedish public
      dental care--a prospective study during a 5-year period of rationalisation.
AB  - In recent decades, comprehensive rationalisations have been implemented in public
      dentistry in Sweden. How rationalisations affect working conditions, health and
      production from a long-term perspective has been poorly investigated. This study
      aims to analyse changes and associations in dentists' working conditions, health
      and productivity during a 5-year period. In 2003 and 2008, 65 dentists responded
      to questionnaires measuring work conditions and health. Treatment times for
      patients and productivity were tracked in electronic registers. Paired t-tests
      showed that the number of treated adult patients per dentist increased, and
      perceived physical working conditions improved while perceived work control and
      leadership deteriorated. Structural equation modelling showed that physical
      factors were important for health and productivity. When assessing risks in the
      work environment, there is a need to understand the interaction of effects on
      working conditions and health due to rationalisations so as to increase the
      sustainability of production systems. PRACTITIONER SUMMARY: Dentistry in Sweden
      has undergone considerable change. Questionnaire surveys with dentists,
      undertaken in 2003 and 2008, found that the present rationalisations resulted in
      improved perceived physical working conditions. Aspects of the psychosocial
      working environment had deteriorated, however. This is a concern as health and
      workability are important for workplace efficiency.

PMID- 23862659
TI  - Guggulipid of Commiphora mukul, with antiallodynic and antihyperalgesic
      activities in both sciatic nerve and spinal nerve ligation models of neuropathic
      pain.
AB  - CONTEXT: Guggulipid is a neutral fraction of ethyl acetate extract of gum resin
      of the tree Commiphora mukul Engl. (Burseraceae) and used in Ayurvedic medicine
      for treatment of neurological disorders. OBJECTIVES: The present study was
      undertaken to assess the antiallodynic and antihyperalgesic activities of
      guggulipid in rats. MATERIALS AND METHODS: The screening study included the CCI
      and L5-L6 SNL models of neuropathic pain. Guggulipid (100 and 50 mg/kg) or saline
      was administered intraperitoneally in a blinded, randomized manner from
      postoperative day (POD) 7 to 13. Paw withdrawal duration (PWD) to spontaneous
      pain, chemical allodynia and mechanical hyperalgesia and paw withdrawal latency
      (PWL) to mechanical allodynia and thermal hyperalgesia were tested before
      surgery, before and after guggulipid or saline administration (from POD7 to 13)
      and after the withdrawal of treatment (from POD14 to 20). RESULTS: The activity
      profiles of the different doses of guggulipid were found to vary with time. In
      CCI rats, guggulipid (100 and 50 mg/kg) significantly (p < 0.05) reduced the
      spontaneous pain, mechanical allodynia and mechanical and thermal hyperalgesia
      responses and the LD50 of guggulipid was 1600 mg/kg. In SNL rats, both doses of
      guggulipid were found to be ineffective in reversing the spontaneous pain but
      showing antiallodynic and antihyperalgesic activity. DISCUSSION AND CONCLUSION:
      The results demonstrated that guggulipid produce antinociception in the
      peripheral nerve injury (CCI and SNL) models of neuropathic pain. The underlying
      mechanisms are expected to be modulating microglial activation occurring due to
      peripheral nerve injury.

PMID- 23862660
TI  - Continuous wave nanowire lasing.
AB  - Tin-doped cadmium sulfide nanowires reveal donor-acceptor pair transitions at low
      temperature photoluminescence and furthermore exhibit ideal resonator morphology
      appropriate for lasing at continuous wave pumping. The continuous wave lasing
      mode is proven by the evolution of the emitted power and spectrum with increasing
      pump intensity. The high temperature stability up to 120 K at given pumping power
      is determined by the decreasing optical gain necessary for lasing in an electron
      hole plasma. 

PMID- 23862661
TI  - Size, shape-dependent growth of semiconductor heterostructures mediated by Ag2Se
      nanocrystals as seeds.
AB  - Size- and shape-controllable Ag2Se-ZnS nanorods (NRs) and nanowires (NWs) have
      been synthesized successfully by the solution-liquid-solid (SLS) method. By using
      Ag2Se nanocrystals (NCs) as seeds and catalyst, colloidal Ag2Se-ZnS NRs and NWs
      with controllable diameters and lengths in ranges of 5-12 nm and 15-600 nm were
      successfully synthesized by altering the experimental variables, such as diameter
      of Ag2Se NCs, amount of precursor, reaction time, and reaction temperature. The
      Ag2Se NCs not only played a key role in the control of the shape of ZnS NCs but
      also influenced the crystal structure of ZnS NCs. The related surface
      photovoltage of heterostructured Ag2Se-ZnS NWs have also been studied and the
      formation of Ag2Se-ZnS heterostructure was confirmed. Moreover, this SLS method
      was successfully exploited to synthesize Ag2S-ZnS heterostructures. 

PMID- 23862662
TI  - Modernization and development: impact on health care decision-making in Uganda.
AB  - Uganda has faced numerous challenges over the past 50 years from overcoming
      political conflict and civil unrest, to rapid population growth, to combating the
      HIV epidemic and ever-growing health needs. Women in Uganda have had a major role
      to play in the health of families and communities. The researchers' purpose in
      this study, undertaken in rural Uganda, was to a) identify a people-centered
      definition of development, b) compare it to the process of modernization, and c)
      investigate how these processes have changed the role women play in decision
      making, in areas directly and indirectly related to their health and that of
      their families. Twenty-two men and women participated in focus group discussion
      and completed questionnaires. Based on our analysis of discussions it appears
      that both modernization and development have impacted health positively and
      negatively. Key themes distilled from interviews included that modernization has
      led to the breakdown of families; increased maternal responsibility for children;
      diminished land and economic resources; and an erosion of cultural values and
      practices that had previously provided stability for the society. In terms of
      development, women play an increasing role in decision-making processes in the
      household and are gaining increasing respect for their expertise in a number of
      areas, notably health care. We propose a movement of grassroots discourse on
      modernization. Development, and its effect on health, is necessary if the
      positive aspects of Ugandan culture and those of similar emerging societies are
      not to be lost (International Covenant on Economic, Social and Cultural Rights,
      1966).

PMID- 23862664
TI  - Sperm quality and its relationship to natural and assisted conception: British
      Fertility Society guidelines for practice.
AB  - Reports on the influence of semen parameters on natural or assisted pregnancy are
      contradictory, suggesting that the many confounding variables which contribute to
      outcome have not been taken into account. However, it is possible to derive some
      consensus for both natural and assisted conception by focussing on studies which
      use WHO-recommended semen analysis on relatively large populations, applying
      appropriate statistics and accounting for 'female factors'. The concentration of
      progressively motile sperm has consistently been shown to be the most predictive
      factor with regard to outcome. Around 64% of studies suggest that a reasonable
      chance of success with artificial insemination requires at least 5 * 106 motile
      sperm and this is supported by the WHO's revised reference range for natural
      conception. Sperm morphology remains controversial, with a lack of
      standardisation across centres, the adoption of ever-stricter scoring criteria
      and changing reference values. Antisperm antibodies do not appear to influence
      outcome independently of sperm motility and agglutination. Sperm DNA damage
      appears to be related to sperm quality, embryo development and pregnancy loss,
      yet there remains no consensus on the best testing procedures, clinical reference
      values and how patients with an adverse result should be managed. In conclusion,
      laboratories should continue to focus on reducing the uncertainty and improving
      the quality of their basic semen analysis.

PMID- 23862663
TI  - The 12-15-lipoxygenase is a modulator of Alzheimer's-related tau pathology in
      vivo.
AB  - 12/15-lipoxygenase (12-15LO) is a lipid-peroxidizing enzyme widely expressed in
      the central nervous system where it has been involved in the neurobiology of
      Alzheimer's disease (AD) because it modulates amyloid beta (Abeta) and APP
      processing. However, its biological effect on tau protein is unknown. We
      investigated the effect of 12-15LO on tau levels and metabolism in vivo and in
      vitro and the mechanism involved by using genetic and pharmacologic approaches.
      While no significant differences were observed in the levels of total tau for
      both groups, compared with controls, Tg2576 mice overexpressing 12-15LO had
      elevated levels of phosphorylated tau at two specific epitopes, Ser 202/Thr 205
      and Ser 396. In vitro and in vivo studies show that 12-15LO modulates tau
      metabolism specifically via the cdk5 kinase pathway. Associated with these
      changes were biochemical markers of synaptic pathology. Finally, 12-15LO
      dependent alteration of tau metabolism was independent from an effect on Abeta.
      Our findings reveal a novel pathway by which 12-15LO modulates endogenous tau
      metabolism making this protein an appealing pharmacologic target for treatment of
      AD and related tauopathies. 

PMID- 23862665
TI  - Blood contact properties of ascorbyl chitosan.
AB  - Ascorbyl chitosan was synthesized by heating chitosan with ascorbic acid in
      isopropanol. The products were characterized by FTIR and C-13 NMR spectroscopies,
      SEM, and elemental analysis. Blood contact properties of ascorbyl chitosans were
      evaluated. The ascorbyl chitosans demonstrated to have increased lipid-lowering
      activity in comparison to chitosan alone upon contact with human blood serum in
      in vitro conditions. Furthermore, the total cholesterol/HDL ratio was improved
      towards the desirable ideal values after three hours contact with ascorbyl
      chitosan samples. The lipid-lowering activity increased with ascorbyl
      substitution. The inherent nonspecific adsorption capability of chitosan due to
      its chelating power with several different functional groups was exhibited by
      ascorbyl chitosans as well. This behavior was exemplified in a simultaneous
      decrease in the total iron values of the volunteers together with lower lipid
      levels. Furthermore, ascorbyl chitosans were observed to have less
      hemocompatibility but increased anticoagulant activity when compared to chitosan
      alone. Additional in vivo studies are necessary to support these results and to
      investigate further the advantages and disadvantages of these materials to prove
      their safety prior to clinical applications. 

PMID- 23862666
TI  - Hepatitis C virus infection is not an independent risk factor for obstructive
      lung disease.
AB  - Several epidemiological studies have suggested that hepatitis C virus (HCV)
      infection is associated with the presence of obstructive lung disease (OLD).
      However, there is a strong link between HCV infection and tobacco abuse, a major
      risk factor for the development of OLD. In this study we analyzed clinical,
      laboratory and spirometric data from 1068 study participants to assess whether
      HCV infection, viremia, or HCV-associated end organ damage were associated with
      OLD. Demographics, risk behavior, serologic status for HCV and HIV, and
      spirometric measurements were collected from a cross-sectional analysis of the
      Acquired Immunodeficiency Syndrome (AIDS) Linked to the IntraVenous Experience
      (ALIVE) study, an observational cohort of IDUs followed in Baltimore, MD since
      1988. Of 1,068 participants, 890 (83%) were HCV positive and 174 (16%) met
      spirometric criteria for OLD. Factors independently associated with OLD were age
      and BMI. HCV infection, viral load and HCV-associated end organ damage were
      similar in participants with and without OLD. In summary, there was no
      independent association between markers of HCV exposure, chronicity, viremia, or
      HCV-associated end-organ damage with OLD. Our findings support the strong
      correlation between HCV status, injection drug use, and smoking. These data
      suggest that HCV may not be a sole contributor to the increased prevalence of OLD
      described in previous studies of HCV-infected individuals.

PMID- 23862667
TI  - Variation in the carbon and oxygen isotope composition of plant biomass and its
      relationship to water-use efficiency at the leaf- and ecosystem-scales in a
      northern Great Plains grassland.
AB  - Measurements of the carbon (delta(13) Cm ) and oxygen (delta(18) Om ) isotope
      composition of C3 plant tissue provide important insights into controls on water
      use efficiency. We investigated the causes of seasonal and inter-annual
      variability in water-use efficiency in a grassland near Lethbridge, Canada using
      stable isotope (leaf-scale) and eddy covariance measurements (ecosystem-scale).
      The positive relationship between delta(13) Cm and delta(18) Om values for
      samples collected during 1998-2001 indicated that variation in stomatal
      conductance and water stress-induced changes in the degree of stomatal limitation
      of net photosynthesis were the major controls on variation in delta(13) Cm and
      biomass production during this time. By comparison, the lack of a significant
      relationship between delta(13) Cm and delta(18) Om values during 2002, 2003 and
      2006 demonstrated that water stress was not a significant limitation on
      photosynthesis and biomass production in these years. Water-use efficiency was
      higher in 2000 than 1999, consistent with expectations because of greater
      stomatal limitation of photosynthesis and lower leaf ci /ca during the drier
      conditions of 2000. Calculated values of leaf-scale water-use efficiency were 2-3
      times higher than ecosystem-scale water-use efficiency, a difference that was
      likely due to carbon lost in root respiration and water lost during soil
      evaporation that was not accounted for by the stable isotope measurements. 

PMID- 23862668
TI  - Clathrate Ba8Au16P30: the "gold standard" for lattice thermal conductivity.
AB  - A novel clathrate phase, Ba8Au16P30, was synthesized from its elements. High
      resolution powder X-ray diffraction and transmission electron microscopy were
      used to establish the crystal structure of the new compound. Ba8Au16P30
      crystallizes in an orthorhombic superstructure of clathrate-I featuring a
      complete separation of gold and phosphorus atoms over different crystallographic
      positions, similar to the Cu-containing analogue, Ba8Cu16P30. Barium cations are
      trapped inside the large polyhedral cages of the gold-phosphorus tetrahedral
      framework. X-ray diffraction indicated that one out of 15 crystallographically
      independent phosphorus atoms appears to be three-coordinate. Probing the local
      structure and chemical bonding of phosphorus atoms with (31)P solid-state NMR
      spectroscopy confirmed the three-coordinate nature of one of the phosphorus
      atomic positions. High-resolution high-angle annular dark-field scanning
      transmission electron microscopy indicated that the clathrate Ba8Au16P30 is well
      ordered on the atomic scale, although numerous twinning and intergrowth defects
      as well as antiphase boundaries were detected. The presence of such defects
      results in the pseudo-body-centered-cubic diffraction patterns observed in single
      crystal X-ray diffraction experiments. NMR and resistivity characterization of
      Ba8Au16P30 indicated paramagnetic metallic properties with a room-temperature
      resistivity of 1.7 mOmega cm. Ba8Au16P30 exhibits a low total thermal
      conductivity (0.62 W m(-1) K(-1)) and an unprecedentedly low lattice thermal
      conductivity (0.18 W m(-1) K(-1)) at room temperature. The values of the thermal
      conductivity for Ba8Au16P30 are significantly lower than the typical values
      reported for solid crystalline compounds. We attribute such low thermal
      conductivity values to the presence of a large number of heavy atoms (Au) in the
      framework and the formation of multiple twinning interfaces and antiphase
      defects, which are effective scatterers of heat-carrying phonons. 

PMID- 23862669
TI  - Deliberate hydroxycarbamide overdose in an adult with essential thrombocythaemia.

PMID- 23862670
TI  - The glucocorticoid analog dexamethasone alters the expression and the
      distribution of dopamine receptors and enkephalin within cortico-subcortical
      regions.
AB  - In humans, glucocorticoid excess may cause neuropsychiatric symptoms, including
      psychosis and cognitive impairment, and glucocorticoid signaling hyperactivation
      may sensitize to substance of abuse. The aim of this work was to evaluate whether
      exposure to glucocorticoid excess triggers molecular changes in dopaminergic and
      opioidergic systems within relevant forebrain areas. We acutely exposed Sprague
      Dawley rats to dexamethasone, a glucocorticoid analog, or vehicle and evaluated
      the mRNA expression of dopamine D1 and D2 receptors and enkephalin within the
      cortex, the striatum, and the midbrain. Dexamethasone reduced mRNA expression of
      D1 receptor and enkephalin in the cortex. In the striatum, dexamethasone reduced
      the expression of D1 receptor mRNA, but not that of D2 receptor and enkephalin.
      No significant changes in D2 receptor mRNA expression were observed in the
      midbrain. Basal distribution of D1 and D2 receptor mRNA showed a clear-cut
      striatal/cortical gradient, while this distribution was less obvious for
      enkephalin mRNA. Dexamethasone increased the cortico-striatal separation in terms
      of D1 and D2 receptor mRNA expression. These molecular changes may represent
      adaptive mechanisms to dexamethasone-induced potentiation of dopaminergic and
      opioidergic transmission, mostly in cortical areas. 

PMID- 23862671
TI  - Expression and function of the transient receptor potential ion channel family in
      the hematologic malignancies.
AB  - Transient receptor potential (TRP) channels are important candidates mediating
      Ca(2+) influx in excitable and nonexcitable cells such as normal and neoplastic
      hematopoietic tissues. They are non selective cation channels implicated in
      Ca(2+) signaling in hematologic tumor cells. Here, we review the growing
      experimental evidence indicating that TRP channels should be included among the
      genes whose expression is altered in hematologic malignancies such as leukemias
      (AML, ALL, CML and CLL), B- and T-lymphomas and multiple myelomas (MM). These
      effects depend on the widespread roles played by the TRP channels in the
      modulation of the proliferation, differentiation and apoptosis of the
      hematopoietic cells. The analysis of the expression of the different TRP channels
      belonging to the TRPMs, TRPVs, TRPCs, TRPPs channel families expressed in
      different hematological malignacies, evidenced a widespread expression of TRPV2
      channel in the myeloid and lymphoid leukemias, and a very peculiar expression of
      this channel in different types of B cell lymphomas and multiple myeloma, that is
      parallel to the restricted expression of TRPV2 in normal immune cells with
      respect to its presence in other human tissues. In vivo studies in children AML
      and ALL patients also evidenced the presence of a genetic polymorphism of the
      TRPM5 gene, that reduced the risk to develop leukemia in the children. Finally,
      the coexpression of TRPV5 and TRPV6 channels in lymphocytes, and their
      involvement in the radioresistance of K562 erythroleukemia cells to ionizing
      radiation exposure is of more interest. Thus in conclusion, the TRP channels
      represent promising targets for hematologic cancer therapy, and their
      exploitation may open to novel pharmaceutical and clinical approaches.

PMID- 23862672
TI  - The bioanalytical molecular pharmacology of the N-methyl-D-aspartate (NMDA)
      receptor nexus and the oxygen-responsive transcription factor HIF-1alpha:
      putative mechanisms and regulatory pathways unravel the intimate hypoxia
      connection.
AB  - Hypoxia-mediated regulation of N-methyl-D-aspartate (NMDA) receptor (NMDAR) is
      phenomenal. NMDAR is no doubt an intriguing paradoxical glutamate receptor (GluR)
      with versatile actions. GluRs play a pivotal role in brain physiology and
      pathophysiology under ischemia and oxygen deprivation, where NMDARs are major
      contributors. Activation of NMDARs is closely associated with the kinetics of
      intracellular calcium (Ca(2+)) release, a main player in neuronal cell death in
      the central nervous system (CNS). However, CNS exposure to hypoxia modulates
      NMDAR/Ca(2+) physiology in such a way that there is a small window of operating
      neuroprotection, rather than the classical neuroinjurious effects manifested upon
      Ca(2+) release. The NMDAR connection with hypoxia-inducible factor-1alpha (HIF
      1alpha), a transcription factor considered master regulator of oxygen sensing
      mechanisms, is not well established in the CNS. However, scanning the literature
      yielded a wealth of NMDAR/hypoxia connection but that with HIF-1alpha is not
      prominent. It is worth mentioning that this is not a comprehensive review on the
      effect of hypoxia on NMDAR physiology, rather this synopsis sheds light on the
      putative mechanisms involving HIF-1alpha and NMDAR regulation. Understanding the
      evidence of this intimate connection and its ramifications may bear potential
      applications in unraveling hypoxia-mediated injury, neuronal cell death and, most
      importantly, adaptive, neuroprotective mechanisms to oxygen deprivation. 

PMID- 23862673
TI  - Assembly of high molecular weight complexes of lipin on a supported lipid bilayer
      observed by atomic force microscopy.
AB  - Lipins are phosphatidic acid phosphatases involved in the biosynthesis of
      triacylglycerols and phospholipids. They are associated with the endoplasmic
      reticulum but can also travel into the nucleus and alter gene expression.
      Previous studies indicate lipins in solution form high molecular weight
      complexes, possibly tetramers. This study was undertaken to determine if lipins
      form complexes on membranes as well. Murine lipin 1b was applied to a supported
      bilayer of phosphatidylcholine, phosphatidylserine, and cholesterol and examined
      by atomic force microscopy (AFM) over time. Lipin on bare mica appeared as a
      symmetric particle with a volume consistent with the size of a monomer. On the
      bilayer, lipin initially bound as asymmetric, curved particles that sometimes
      assembled into circular structures with an open center. Subsequently, lipin
      assemblies grew into large, symmetric particles with an average volume 12 times
      that of the monomer. Over time, some of the lipin assemblies were removed from
      the bilayer by the AFM probe leaving behind "footprints" composed of complex
      patterns that may reflect the substructure of the lipin assemblies. The lipin
      complexes appeared very flat, with a diameter 20 times their height. The
      footprints had a similar diameter, providing confirmation of the extensive
      deformation of the protein under the AFM probe. The ability of lipin to form
      large complexes on membranes may have significant implications for the local
      concentrations of the product, diacylglycerol, formed during hydrolysis of
      phosphatidic acid and for cooperative hormonal regulation of lipin activity
      through phosphorylation of one or more monomers in the complexes. 

PMID- 23862674
TI  - Topology and dynamics of signaling networks: in search of transcriptional control
      of the inflammatory response.
AB  - Over the past several decades, to develop a fundamental understanding of
      inflammation's progression, research has focused on extracellular mediators, such
      as cytokines, as characteristic components of inflammatory response. These
      efforts have recently been complemented by advances in proteomics that allow
      analysis of multiple signaling proteins in parallel, to provide more complete
      mechanistic models of inflammation. In this review, we discuss various techniques
      for assessing protein activity, as well as computational techniques that are well
      suited for interpreting large amounts of proteomic data to generate signaling
      networks or for modeling the dynamics of known network interactions. We also
      discuss examples that explore these experimental and computational techniques in
      tandem to generate signaling networks under various conditions and that link
      those networks to transcriptional activity. Further advancements in this field
      will likely provide an explicit description of inflammatory response, paving the
      way for better diagnostics and therapies in clinic. 

PMID- 23862675
TI  - Systems biology characterization of engineered tissues.
AB  - Tissue engineering and molecular systems biology are inherently interdisciplinary
      fields that have been developed independently so far. In this review, we first
      provide a brief introduction to tissue engineering and to molecular systems
      biology. Next, we highlight some prominent applications of systems biology
      techniques in tissue engineering. Finally, we outline research directions that
      can successfully blend these two fields. Through these examples, we propose that
      experimental and computational advances in molecular systems biology can lead to
      predictive models of bioengineered tissues that enhance our understanding of
      bioengineered systems. In turn, the unique challenges posed by tissue engineering
      will usher in new experimental techniques and computational advances in systems
      biology. 

PMID- 23862676
TI  - Biophysical cues and cell behavior: the big impact of little things.
AB  - The extracellular matrix is composed of a variety of proteins, polysaccharides,
      and glycosaminoglycans that self-assemble into a hierarchical order of nanometer-
      to micrometer-scale fibrils and fibers. The shapes, sizes, and elasticity present
      within this highly ordered meshwork regulate behaviors in most cell types. It has
      been well documented that cellular migration, proliferation, differentiation, and
      tissue development are all influenced by matrix geometries and compliance, but
      how these external biophysical cues are translated into activated intracellular
      signaling cascades remains poorly understood. Fortunately, technological
      improvements in artificial substrate fabrication have provided biologists with
      tools to test cellular interactions within controlled three-dimensional
      environments. Here, we review cellular responses to biophysical cues and discuss
      their clinical relevancy and application. We focus especially on integrative
      approaches that aim to first characterize the properties of specific
      extracellular matrices and then precisely fabricate biomimetic materials to
      elucidate how relevant cells respond to the individual biophysical cues present
      in their native tissues. Through these types of comprehensive studies, biologists
      have begun to understand and appreciate how exceedingly small features can have a
      significant impact on the regulation, development, and homeostasis of cells and
      tissues. 

PMID- 23862679
TI  - Formation and mitigation of heterocyclic aromatic amines in fried pork.
AB  - Heterocyclic aromatic amines (HAAs) are potent mutagens and carcinogens generated
      during the heat processing of meat. HAAs, which are abundant in processed meat
      products, include 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino
      3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), and 2-amino-1-methyl-6
      phenylimidazo [4,5-b] pyridine (PhIP). The content of these three HAAs in fried
      pork was determined by LC-MS/MS. The effects of frying time and temperature,
      sample shape, and addition of antioxidants on the generation of HAAs were
      investigated. The results show that HAAs were produced during frying, and their
      levels increased with increasing frying time and temperature. Pork patties had
      the highest concentration of HAAs compared with pork meatballs and pork strips.
      The addition of antioxidant of bamboo leaves (AOB), liquorice extract, tea
      polyphenol, phytic acid and sodium iso-ascorbate to pork before frying had an
      inhibitory effect on HAA generation, with AOB being the most effective
      antioxidant. Inhibition levels of nearly 69.73% for MeIQx, 53.59% for 4,8-DiMeIQx
      and 77.07% for PhIP in fried pork were achieved when the concentrations of AOB
      added were 0.02, 0.01 and 0.10 g kg-1, respectively.

PMID- 23862678
TI  - Sensors and decoding for intracortical brain computer interfaces.
AB  - Intracortical brain computer interfaces (iBCIs) are being developed to enable
      people to drive an output device, such as a computer cursor, directly from their
      neural activity. One goal of the technology is to help people with severe
      paralysis or limb loss. Key elements of an iBCI are the implanted sensor that
      records the neural signals and the software that decodes the user's intended
      movement from those signals. Here, we focus on recent advances in these two
      areas, placing special attention on contributions that are or may soon be adopted
      by the iBCI research community. We discuss how these innovations increase the
      technology's capability, accuracy, and longevity, all important steps that are
      expanding the range of possible future clinical applications. 

PMID- 23862677
TI  - Micro- and nanoscale engineering of cell signaling.
AB  - It is increasingly recognized that cell signaling, as a chemical process, must be
      considered at the local, micrometer scale. Micro- and nanofabrication techniques
      provide access to these dimensions, with the potential to capture and manipulate
      the spatial complexity of intracellular signaling in experimental models. This
      review focuses on recent advances in adapting surface engineering for use with
      biomolecular systems that interface with cell signaling, particularly with
      respect to surfaces that interact with multiple receptor systems on individual
      cells. The utility of this conceptual and experimental approach is demonstrated
      in the context of epithelial cells and T lymphocytes, two systems whose ability
      to perform their physiological function is dramatically impacted by the
      convergence and balance of multiple signaling pathways. 

PMID- 23862680
TI  - Targeting RNA polymerase I transcription and the nucleolus for cancer therapy.
AB  - The nucleoli are the site of the production of ribosomes, the protein synthetic
      apparatus of the cell. The presence of enlarged nucleoli, reflecting increased
      ribosomal gene transcription, has long been used by pathologists as an indicator
      of aggressive tumors. However, over the last 10 years a growing body of evidence
      has revealed that the nucleolus contains a dynamic cohort of over 4500 proteins,
      the majority of which have no function in ribosome production. The activity of
      some of these proteins is modulated by their regulated sequestration and release
      from the nucleolus. In particular, the nucleolus plays a central role in sensing
      cellular stress to modulate the abundance of the critical tumor suppressor
      protein p53. The finding that p53 activity is dysregulated in up to 50% of all
      human cancers highlights the importance of the nucleolar stress response in
      limiting malignant transformation. The development of drugs to selectively
      inhibit transcription of the ribosomal RNA genes in the nucleolus has paved the
      way for a new therapeutic approach to hijack nucleolar stress to selectively and
      non-genotoxically activate p53 in tumor cells. Here, we describe the potential
      application of this exciting new class of drugs for the treatment of human
      cancer. 

PMID- 23862682
TI  - Luffa-sponge-like glass-TiO2 composite fibers as efficient photocatalysts for
      environmental remediation.
AB  - Structural design of photocatalysts is of great technological importance for
      practical applications. A rational design of architecture can not only promote
      the synthetic performance of photocatalysts but also bring convenience in their
      application procedure. Nanofibers have been established as one of the most ideal
      architectures of photocatalysts. However, simultaneous optimization of the
      photocatalytic efficiency, mechanical strength, and thermal/chemical tolerance of
      nanofibrous photocatalysts remains a big challenge. Here, we demonstrate a novel
      design of TiO2-SiO2 composite fiber as an efficient photocatalyst with excellent
      synthetic performance. Core-shell mesoporous SiO2 fiber with high flexibility was
      employed as the backbone for supporting ultrasmall TiO2 nanowhiskers of the
      anatase phase, constructing core@double-shell fiber with luffa-sponge-like
      appearance. Benefitting from their continuously long fibrous morphology, highly
      porous structure, and completely inorganic nature, the TiO2-SiO2 composite fibers
      simultaneously possess high photocatalytic reactivity, good flexibility, and
      excellent thermal and chemical stability. This novel architecture of TiO2-SiO2
      glass composite fiber may find extensive use in the environment remediation
      applications. 

PMID- 23862683
TI  - Cleome arabica leaf extract has anticancer properties in human cancer cells.
AB  - CONTEXT: Cleome arabica L. (Capparidaceae) is a desert plant widely distributed
      in the North part of Africa whose leaves are used in traditional medicine as a
      sedative for abdominal and rheumatic pains. OBJECTIVES: The anticancer activity
      of methanol Cleome arabica leaf extracts (CALE) is investigated in different
      human cancer cell lines. MATERIALS AND METHODS: Five different human cancer cell
      lines, representative of the most common cancers in Western countries (i.e.,
      breast adenocarcinoma, colon carcinoma, neuroblastoma, hepatoma, cervix
      carcinoma) were treated with different concentrations of CALE (i.e., 1, 5, 10,
      25, 50, 100 and 200 ug/ml). Cell viability and cell cycle were measured by using
      a hemocytometer chamber and a cytofluorimeter, respectively. Epidermal growth
      factor (EGF) was used as a positive control. Western blots were performed to
      evaluate the CALE effects on pathways involved in cell growth regulation and on
      apoptotic cascade activation. RESULTS AND CONCLUSION: Our results confirm that
      CALE has a high content of polyphenolic compounds (i.e., 32.21 +/- 3.44%), mainly
      as flavonoids (24.56 +/- 4.67%). In all tested cell lines CALE treatment reduces
      cell number in a dose-dependent manner (ED50 = 175 +/- 30 ug/ml). CALE (100 and
      200 ug/ml) increases by three-fold the activation of the apoptotic cascade
      involving caspase-3 activation and the cleavage of its substrate poly(ADP-ribose)
      polymerase (PARP). Intriguingly, CALE treatment (200 ug/ml) also blocks EGF
      induced cell growth by preventing the growth factor-triggered AKT and ERK
      phosphorylation. As a whole, these data strongly suggest that CALE possesses
      anticancer effects in all tested cancer cell lines.

PMID- 23862684
TI  - Aryne insertion reactions leading to bioactive fused quinazolinones:
      diastereoselective total synthesis of cruciferane.
AB  - Insertion reactions of an in situ generated arynes to a variety of suitably
      substituted 1,3-quinazolin-4-ones have been demonstrated for a new efficient one
      step approach to a diverse range of fused quinazolinone architectures. The
      present protocol has been effectively utilized to accomplish the concise total
      synthesis of recently isolated bioactive natural products tryptanthrin,
      phaitanthrins A-C, and cruciferane. 

PMID- 23862685
TI  - Modeling the balanced inventory of desirable responding: evidence in favor of a
      revised model of socially desirable responding.
AB  - Paulhus (1984) proposed a 2-factor model of socially desirable responding (SDR)
      and created the Balanced Inventory of Desirable Responding (BIDR) to capture the
      2 dimensions: self-deceptive enhancement and impression management. However, the
      2-factor model has yet to be supported via confirmatory factor analysis (CFA) of
      the BIDR. Paulhus and Reid (1991) proposed a revised model of SDR, which
      bifurcated the self-deceptive enhancement dimension into 2 factors: self
      deceptive enhancement (SDE; positively keyed items) and self-deceptive denial
      (SDD; negatively keyed items). Thus, it was considered useful to test the revised
      SDR model on the BIDR, as this might have implications for the manner in which
      the BIDR should be scored. Additionally, as the BIDR subscales might be
      positively correlated, it was considered useful from a both a theoretical and
      practical perspective to test the possibility that the BIDR might measure a
      general SDR process. Based on a sample of 466 adults, Paulhus and Reid's revised
      model of SDR was largely supported when tested via CFA on a bifactor model, which
      included a first-order general SDR factor and 2 nested factors. Thus, applied
      researchers might consider using total BIDR composite scores, a self-deceptive
      enhancement composite score (positively keyed items), and impression management
      composite scores. However, ideally, researchers would use a bifactor model to
      test substantive hypotheses, as the bifactor model partitions true score variance
      into unique sources, which facilitates less ambiguous interpretations of effects.

PMID- 23862686
TI  - Akt regulates TPP1 homodimerization and telomere protection.
AB  - Telomeres are specialized structures at the ends of eukaryotic chromosomes that
      are important for maintaining genome stability and integrity. Telomere
      dysfunction has been linked to aging and cancer development. In mammalian cells,
      extensive studies have been carried out to illustrate how core telomeric proteins
      assemble on telomeres to recruit the telomerase and additional factors for
      telomere maintenance and protection. In comparison, how changes in growth
      signaling pathways impact telomeres and telomere-binding proteins remains largely
      unexplored. The phosphatidylinositol 3-kinase (PI3-K)/Akt (also known as PKB)
      pathway, one of the best characterized growth signaling cascades, regulates a
      variety of cellular function including cell proliferation, survival, metabolism,
      and DNA repair, and dysregulation of PI3-K/Akt signaling has been linked to aging
      and diseases such as cancer and diabetes. In this study, we provide evidence that
      the Akt signaling pathway plays an important role in telomere protection. Akt
      inhibition either by chemical inhibitors or small interfering RNAs induced
      telomere dysfunction. Furthermore, we found that TPP1 could homodimerize through
      its OB-fold, a process that was dependent on the Akt kinase. Telomere damage and
      reduced TPP1 dimerization as a result of Akt inhibition was also accompanied by
      diminished recruitment of TPP1 and POT1 to the telomeres. Our findings highlight
      a previously unknown link between Akt signaling and telomere protection. 

PMID- 23862687
TI  - Kinetic resolution in asymmetric epoxidation using iminium salt catalysis.
AB  - The first reported examples of kinetic resolution in epoxidation reactions using
      iminium salt catalysis are described, providing up to 99% ee in the epoxidation
      of racemic cis-chromenes. 

PMID- 23862688
TI  - Lutein protects retinal pigment epithelium from cytotoxic oxidative stress.
AB  - CONTEXT: Lutein (LUT) and zeaxanthin (ZEA) are currently under investigation in
      clinical trials as prophylactic nutritional agents for age-related macular
      degeneration (AMD). However, dose used in these trials is empirical and not been
      investigated in in vitro studies. OBJECTIVE: In this study, we investigated the
      dose-response effect of LUT and ZEA in protecting retinal pigment epithelium
      (RPE) from oxidative stress, a common underlying pathology in AMD. METHODS: Three
      thousand cultured human retinal pigment epithelial cells (ARPE-19) were plated in
      72-well plate and after 24 h were exposed to increasing concentrations of
      hydrogen peroxide (H2O2). ARPE-19 cells were exposed to four different
      concentrations of LUT (0.5, 1, 2 and 4 ug/mL) and ZEA (0.1, 0.2, 0.4 and 0.8
      ug/mL). After 24 h incubation, cells were subjected to oxidative stress induced
      with H2O2. Cultures containing saline solution and dichloromethane served as
      controls. Cell viability was assessed using the WST-1 assay. Pathophysiological
      pathways were evaluated by measuring caspase-3 levels as an indicator of
      apoptosis induction. Reactive oxygen species (ROS) levels were measured using
      dihydrorhodamine-123. RESULTS: Cell viability as a percentage of control was
      81.3%, 81.1%, and 88.8% at 0.5, 1, and 2 ug/ml, respectively of LUT (p < 0.001).
      The maximum cytoprotective effect was seen with LUT at 2 MUg/mL. ZEA did not show
      any cytoprotective effect at all concentrations used in the study. Caspase-3
      showed a corresponding decrease in levels with LUT (1 and 2 ug/ml). Significant
      decrease in ROS levels were measured only with LUT at 4 ug/ml (p = 0.02).
      DISCUSSION AND CONCLUSIONS: Results from our study provide in vitro data to
      support the epidemiologic studies, which are currently underway to provide
      evidence that lutein may act as cofactor that modulates processes implicated in
      AMD pathogenesis.

PMID- 23862689
TI  - TLR5 stop codon polymorphism is associated with invasive aspergillosis after
      allogeneic stem cell transplantation.
AB  - Single nucleotide polymorphisms (SNPs) have been associated with an increased
      incidence of invasive aspergillosis (IA) after allogeneic stem cell
      transplantation (allo-SCT). We analyzed 41 patients with proven/probable IA after
      allo-SCT for an association of SNPs, within the TLR2, TLR4, TLR5, TLR9, and
      NOD2/CARD15 genes, with susceptibility to IA. The control group consisted of 130
      patients who had allo-SCT but did not develop IA. While no association was found
      for donor SNPs and the recipients' risk of IA, analysis of recipient SNPs showed
      a significant association between the presence of recipient TLR5-Stop SNP (1174C>
      T) and the incidence of IA (P = 0.004). Multivariate analysis demonstrated that
      the recipient TLR5-Stop SNP appeared as an independent risk factor for IA after
      allo-SCT. Our study suggests that TLR5 is involved in host defense against
      Aspergillus fumigatus, and that the recipient TLR5-Stop SNP represents a risk
      factor for the development of IA after allo-SCT.

PMID- 23862691
TI  - Neutral and ionized hydrides in star-forming regions. Observations with
      Herschel/HIFI.
AB  - The cosmic abundance of hydrides depends critically on high-energy UV, X-ray, and
      particle irradiation. Here we study hydrides in star-forming regions where
      irradiation by the young stellar object can be substantial, and density and
      temperature can be much enhanced over interstellar values. Lines of OH, CH, NH,
      and SH and their ions OH(+), CH(+), NH(+), SH(+), H2O(+), and H3O(+) were
      observed in star-forming regions by the HIFI spectrometer onboard the Herschel
      Space Observatory. Molecular column densities are derived from observed ground
      state lines, models, or rotational diagrams. We report here on two prototypical
      high-mass regions, AFGL 2591 and W3 IRS5, and compare them to chemical
      calculations by making assumptions on the high-energy irradiation. A model
      assuming no ionizing protostellar emission is compared with (i) a model assuming
      strong protostellar X-ray emission and (ii) a two-dimensional (2D) model
      including emission in the far UV (FUV, 6-13.6 eV), irradiating the outflow walls
      that separate the outflowing gas and infalling envelope material. We confirm that
      the effect of FUV in two-dimensional models with enlarged irradiated surfaces is
      clearly noticeable. A molecule that is very sensitive to FUV irradiation is
      CH(+), enhanced in abundance by more than 5 orders of magnitude. The HIFI
      observations of CH(+) lines agree with the two-dimensional FUV model by Bruderer
      et al., which computes abundances, non-LTE excitation, and line radiative
      transfer.20 It is concluded that CH(+) is a good FUV tracer in star-forming
      regions. The effect of potential X-ray irradiation is not excluded but cannot be
      demonstrated by the present data. 

PMID- 23862690
TI  - Scope and mechanism of the Pt-catalyzed enantioselective diboration of
      monosubstituted alkenes.
AB  - The Pt-catalyzed enantioselective diboration of terminal alkenes can be
      accomplished in an enantioselective fashion in the presence of chiral phosphonite
      ligands. Optimal procedures and the substrate scope of this transformation are
      fully investigated. Reaction progress kinetic analysis and kinetic isotope
      effects suggest that the stereodefining step in the catalytic cycle is olefin
      migratory insertion into a Pt-B bond. Density functional theory analysis,
      combined with other experimental data, suggests that the insertion reaction
      positions platinum at the internal carbon of the substrate. A stereochemical
      model for this reaction is advanced that is in line both with these features and
      with the crystal structure of a Pt-ligand complex. 

PMID- 23862692
TI  - Comparison of established and emerging biodosimetry assays.
AB  - Rapid biodosimetry tools are required to assist with triage in the case of a
      large-scale radiation incident. Here, we aimed to determine the dose-assessment
      accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis
      block micronucleus assay (CBMN) in comparison to the emerging gamma-H2AX foci and
      gene expression assays for triage mode biodosimetry and radiation injury
      assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of
      up to 6.4 Gy were sent to participants for dose estimation. Report times were
      documented for each laboratory and assay. The mean absolute difference (MAD) of
      estimated doses relative to the true doses was calculated. We also merged doses
      into binary dose categories of clinical relevance and examined accuracy,
      sensitivity and specificity of the assays. Dose estimates were reported by the
      first laboratories within 0.3-0.4 days of receipt of samples for the gamma-H2AX
      and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN
      assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation
      of interlaboratory accuracy per assay and lowest MAD values for the DCA assay
      (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and gamma-H2AX
      (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated
      with equal efficiency for all assays, but at doses >=1.5 Gy a 10% decrease in
      efficiency was observed for the foci assay, which was still comparable to the
      CBMN assay. In conclusion, the DCA has been confirmed as the gold standard
      biodosimetry method, but in situations where speed and throughput are more
      important than ultimate accuracy, the emerging rapid molecular assays have the
      potential to become useful triage tools. 

PMID- 23862694
TI  - Cyclodextrin-cross-linked diaminotriazine-based hydrogen bonding strengthened
      hydrogels for drug and reverse gene delivery.
AB  - A hydrogen bonding strengthened hydrogel was prepared by radical copolymerization
      of poly(ethylene glycol) methacrylated beta-cyclodextrin (PEG-beta-CD) and 2
      vinyl-4,6-diamino-1,3,5-triazine (VDT) monomer. PEG-beta-CD served not only as a
      cross-linker, but also as a built-in solubilizing agent of the hydrophobic drug
      in the gel. Increasing VDT content resulted in a notable enhancement in the
      mechanical strengths of hydrogels whose equilibrium water contents could be
      modulated from 75% to 85% by varying the ratio of PEG-beta-CD cross-linker. It
      was shown that copolymerizing more PEG-beta-CDs could load higher amount of
      ibuprofen (IBU) in the gels and contribute to a slower release rate of IBU.
      Plasmid DNA could be anchored onto the surface of hydrogels due to the hydrogen
      bonding between the base pairs and diaminotriazine, thereby mediating efficient
      reverse gene transfection of luciferase gene in COS-7 cells cultured on the gel
      surface. The cytocompatible PEG-beta-CD-cross-linked PVDT hydrogels with
      multifunction of drug and gene delivery hold a potential as tissue engineering
      scaffold. 

PMID- 23862695
TI  - Core structure and surface functionalization of carbon nanomaterials alter
      impacts to daphnid mortality, reproduction, and growth: acute assays do not
      predict chronic exposure impacts.
AB  - There are currently over ninety products incorporating carbon nanomaterials
      (CNMs) on the market today for a variety of applications. Modifications in core
      structure and surface chemistry of manufactured nanomaterials are used to
      optimize nanomaterials for specific uses. However, there is a notable lack of
      information on how core structure and surface chemistry may alter toxicity in low
      level, chronic exposures. This paper examines the effects of twelve CNMs that
      differ in their core structure and surface chemistry to Daphnia magna over a 21
      day chronic exposure. Overall, nanomaterials with a carbon nanotube core were
      more toxic to daphnids than fullerenes, with the one exception of fullerenes with
      a gamma-cyclodextrin surface chemistry. Acute mortality was not a good predictor
      of chronic effects as none of the CNMs induced toxicity at tested concentrations
      after 48 h, yet chronic assays indicated significant differences in mortality,
      reproduction, and growth realized after 21 days. Our results indicate that (1)
      acute exposure assays do not accurately describe the impact of CNMs to biological
      systems, (2) chronic exposures provide valuable information that indicates the
      potential for different modes of action for nanomaterials of differing
      chemistries, and (3) core structure and surface chemistry both influence particle
      toxicity. 

PMID- 23862696
TI  - The committee for advanced therapies' of the European Medicines Agency reflection
      paper on management of clinical risks deriving from insertional mutagenesis.
AB  - In the European Union, the Committee for Advanced Therapies of the European
      Medicines Agency takes the lead in the scientific assessment for marketing
      authorization applications for advanced therapy medicinal products, which include
      gene therapy medicinal products, somatic cell therapy medicinal products, and
      tissue-engineered products. The Committee for Advanced Therapies also takes the
      lead in defining the scientific framework for the quality, nonclinical and
      clinical development of such products. This reflection paper represents the
      Committee's current thinking on management of clinical risks deriving from
      insertional mutagenesis. A multidisciplinary approach to insertional mutagenesis
      is provided. This reflection paper has been adopted by the committee in its April
      2013 meeting.

PMID- 23862693
TI  - Conditional radioresistance of Tet-inducible manganese superoxide dismutase bone
      marrow stromal cell lines.
AB  - Mitochondrial targeted manganese superoxide dismutase is a major antioxidant
      enzyme, the levels of which modulate the response of cells, tissues and organs to
      ionizing irradiation. We developed a Tet-regulated MnSOD mouse (MnSOD(tet)) to
      examine the detailed relationship between cellular MnSOD concentration and
      radioresistance and carried out in vitro studies using bone marrow culture
      derived stromal cell lines (mesenchymal stem cells). Homozygous MnSOD(tet/tet)
      cells had low levels of MnSOD, reduced viability and proliferation, increased
      radiosensitivity, elevated overall antioxidant stores, and defects in cell
      proliferation and DNA strand-break repair. Doxycycline (doxy) treatment of
      MnSOD(tet/tet) cells increased MnSOD levels and radioresistance from n of 2.79 +/
      1.04 to 8.69 +/- 1.09 (P = 0.0060) and normalized other biologic parameters. In
      contrast, MnSOD(tet/tet) cells showed minimal difference in baseline and
      radiation induced mRNA and protein levels of TGF-beta, Nrf2 and NF-kappaB and
      radiation induced cell cycle arrest was not dependent upon MnSOD level. These
      novel MnSOD(tet/tet) mouse derived cells should be valuable for elucidating
      several parameters of the oxidative stress response to ionizing radiation. 

PMID- 23862697
TI  - HotLig: a molecular surface-directed approach to scoring protein-ligand
      interactions.
AB  - Accurate prediction of ligand-binding poses is crucial for understanding
      molecular interactions and is very important for drug discovery, structural
      design, and optimization. In this study, we developed a novel scoring program,
      HotLig, which applies the Connolly surface of a protein to calculate hydrophobic
      interaction and paired pharmacophore interactions with ligands. In addition to
      molecular surface distance, ligand-contacting areas and hydrogen-bond angles were
      also introduced to the scoring functions in HotLig. Four individual energy
      scoring functions for H-bonds, ionic pairs, metal coordination, and hydrophobic
      effects were derived from 600 protein-ligand complexes, and then, their weighting
      factors were optimized through an interaction-characterized training set. Success
      rates of ligand-binding-pose predictions (with a root mean squared deviation of
      <=2 A) for the Wang, GOLD, and Cheng data sets were respectively validated to be
      91.0%, 87.0%, and 85.6%. HotLig was found to possess equally good predictive
      powers for the hydrophilic (88.6%) and hydrophobic subsets (87.5%), and the
      success rate for the mixed subset was as high as 96.9%. The Spearman correlation
      coefficients were as good as 0.609 to 0.668, which indicates HotLig also has
      satisfactory predictive power for binding affinities. These results suggested
      that the HotLig can analyze diverse ligands, including peptides, and is expected
      to be a powerful tool for drug design and discovery. 

PMID- 23862698
TI  - Nanostructuring the surface of dual responsive hollow polymer microspheres for
      versatile utilization in nanomedicine-related applications.
AB  - The design and fabrication of hollow polymer microspheres responsive to various
      stimuli comprises a promising approach for the development of multifunctional and
      efficient systems for various nanomedicine-related applications. In this paper,
      we present the preparation of poly(methacrylic acid-co-N,N'
      methylenebis(acrylamide)-co-poly(ethylene glycol) methyl ether methacrylate-co
      N,N'-bis(acryloyl)cystamine) (PMAA(S-S)) hollow microspheres following a two
      stage distillation precipitation polymerization procedure. Magnetic and silver
      nanocrystals were chemically grown on the surface of the hollow polymer
      microspheres, resulting in a composite system with interesting properties. We
      evaluated the performance of the composite hollow microspheres as magnetic
      hyperthermia mediators and their surface-enhanced Raman spectroscopy activity.
      Assessment of Daunorubicin-loaded PMAA(S-S) hollow microspheres performance as
      effective drug carriers was carried out through drug release experiments upon
      application of different pH and reducing conditions. pH and redox responsiveness
      as well as basic mechanisms of release profiles are discussed. Furthermore, in
      vitro cytotoxicity of empty and drug-loaded PMAA(S-S) hollow microspheres against
      MCF-7 cancer cells was investigated in order to evaluate their performance as
      drug carriers.

PMID- 23862699
TI  - Differences in specificity and selectivity between CBP and p300 acetylation of
      histone H3 and H3/H4.
AB  - Although p300 and CBP lysine acetyltransferases are often treated
      interchangeably, the inability of one enzyme to compensate for the loss of the
      other suggests unique roles for each. As these deficiencies coincide with
      aberrant levels of histone acetylation, we hypothesized that the key difference
      between p300 and CBP activity is differences in their specificity/selectivity for
      lysines within the histones. Utilizing a label-free, quantitative mass
      spectrometry based technique, we determined the kinetic parameters of both CBP
      and p300 at each lysine of H3 and H4, under conditions we would expect to
      encounter in the cell (either limiting acetyl-CoA or histone). Our results show
      that while p300 and CBP acetylate many common residues on H3 and H4, they do in
      fact possess very different specificities, and these specificities are dependent
      on whether histone or acetyl-CoA is limiting. Steady-state experiments with
      limiting H3 demonstrate that both CBP and p300 acetylate H3K14, H3K18, H3K23,
      with p300 having specificities up to 1010-fold higher than CBP. Utilizing
      tetramer as a substrate, both enzymes also acetylate H4K5, H4K8, H4K12, and
      H4K16. With limiting tetramer, CBP displays higher specificities, especially at
      H3K18, where CBP specificity is 1032-fold higher than p300. With limiting acetyl
      CoA, p300 has the highest specificity at H4K16, where specificity is 1018-fold
      higher than CBP. This discovery of unique specificity for targets of CBP- vs p300
      mediated acetylation of histone lysine residues presents a new model for
      understanding their respective biological roles and possibly an opportunity for
      selective therapeutic intervention.

PMID- 23862700
TI  - Value of pharmacokinetic studies for patients with gastrointestinal stromal
      tumors.

PMID- 23862701
TI  - Toward innovation in bioanalysis: from operational excellence to process insight.

PMID- 23862703
TI  - Ask the experts: increasing and maintaining productivity in the bioanalytical
      laboratory.
AB  - Bioanalysis invited a selection of leading researchers to express their views on
      increasing and maintaining productivity in the bioanalytical laboratory. The
      topics discussed include the challenges of maintaining productivity when
      integrating new innovations into existing processes, the impact of automation on
      productivity, and how they effectively manage productivity in their own
      bioanalytical laboratories. Their enlightening responses provide a valuable
      insight into current methods of increasing productivity and the future of the
      constantly evolving bioanalytical laboratory. 

PMID- 23862704
TI  - Bioanalysis Young Investigator: AWARD 2013.

PMID- 23862705
TI  - Comparison of sample preparation approaches for bioanalytical workflows and their
      affect on productivity.

PMID- 23862706
TI  - A generic template for automated bioanalytical ligand-binding assays using
      modular robotic scripts in support of discovery biotherapeutic programs.
AB  - BACKGROUND: Sample dilution and reagent pipetting are time-consuming steps in
      ligand-binding assays (LBAs). Traditional automation-assisted LBAs use assay
      specific scripts that require labor-intensive script writing and user training.
      RESULTS: Five major script modules were developed on Tecan Freedom EVO liquid
      handling software to facilitate the automated sample preparation and LBA
      procedure: sample dilution, sample minimum required dilution, standard/QC minimum
      required dilution, standard/QC/sample addition, and reagent addition. The modular
      design of automation scripts allowed the users to assemble an automated assay
      with minimal script modification. The application of the template was
      demonstrated in three LBAs to support discovery biotherapeutic programs.
      CONCLUSION: The results demonstrated that the modular scripts provided the
      flexibility in adapting to various LBA formats and the significant time saving in
      script writing and scientist training. Data generated by the automated process
      were comparable to those by manual process while the bioanalytical productivity
      was significantly improved using the modular robotic scripts.

PMID- 23862707
TI  - Rapid development of multiple 'fit-for-purpose' assays on an automatic
      microfluidic system using a streamlined process in support of early
      biotherapeutics discovery programs.
AB  - BACKGROUND: With a rapid increase in the number of novel biotherapeutic programs
      in the pipelines, efficient development of ligand-binding assays for PK and PD
      studies in the early discovery stage has become more important than ever.
      METHODOLOGY: A four-step process was evaluated to quickly develop multiple 'fit
      for-purpose' Gyrolab((r)) ligand-binding assays in parallel. It covered the
      following four steps: reagent labeling, reagent screening, assay optimization;
      and, assay qualification. RESULTS: Eight assays for two programs were developed
      and qualified in less than 2 weeks. These assays met the specifications of
      sufficient sensitivity with LLOQ between 2 and 50 ng/ml, %CV <25% and recoveries
      between 75 and 125% for QC samples. CONCLUSION: The streamlined four-step process
      enabled timely development of multiple high-throughput assays in parallel with
      minimal hands-on time. Consequently, it dramatically increased assay development
      productivity to support the discovery programs.

PMID- 23862708
TI  - The GyrolabTM immunoassay system: a platform for automated bioanalysis and rapid
      sample turnaround.
AB  - BACKGROUND: The GyrolabTM workstation benefits from fully automated transfer of
      reagents and samples originating from a storage microplate onto a compact disc
      containing solid-phase microstructures composed of a 15 nl streptavidin
      derivitized bead bed. RESULTS: This paper describes the development, full
      validation and use of the method in a regulated environment to measure a
      humanized bispecific monoclonal antibody-domain antibody (GSK-A) molecule using
      the Gyrolab immunoassay system in cynomolgus nonhuman primate plasma ranging from
      5 to 250 ug/ml. The method was subsequently used in support of the TK portion of
      a regulated preclinical study in monkeys. CONCLUSION: The Gyrolab immunoassay
      system proved to be a viable alternative to traditional immunoassays and was used
      to support a regulated preclinical TK study. The speed of analysis that the
      Gyrolab provides was beneficial in meeting timelines to complete this project as
      multiple assays and repeat sample analysis could be completed in the same day.

PMID- 23862709
TI  - Automate it: ligand-binding assay productivity in a discovery bioanalytical
      setting.
AB  - In multiple industries, including the biopharmaceutical industry, automation is
      synonymous with increased productivity. Environments with high-throughput needs
      commonly employ automation for efficiency. However, in a discovery bioanalytical
      ligand-binding assay laboratory setting where the focus is not necessarily on
      sample analysis throughput, but instead on assay development and
      characterization, is automation applicable? Can automation enhance productivity
      when tasks are more customized than routine? In this Perspective we review the
      different categories of automation with ligand-binding assays with these
      questions in mind. In considering whether automation technology has progressed
      far enough to result in a positive return in investment in the discovery setting,
      the resource investment required to operate in this space was contrasted with the
      gain in productivity. In our opinion, technology advancements in automated
      technology platforms, and especially personal automation, have allowed these
      categories to strike the right balance for investment in the discovery laboratory
      setting. 

PMID- 23862710
TI  - Standardized workflows for increasing efficiency and productivity in discovery
      stage bioanalysis.
AB  - Merck consolidated discovery stage bioanalytical functions into the Department of
      Pharmacokinetics, Pharmacodynamics & Drug Metabolism in 2007. Since then
      procedures and equipment used to provide important quantitative data to project
      teams have been harmonized and in many cases standardized. This approach has
      enabled movement of work across the network of laboratories and has resulted in a
      lean, flexible and efficient organization. The overall goal was to reduce time
      and resources spent on routine activities while creating time to perform research
      in new areas and technologies to support future scientific needs. The current
      state of discovery bioanalysis at Merck is discussed, including hardware and
      software platforms, workflow procedures and performance metrics. Examples of
      improved processes will be discussed for compound tuning, LC method development,
      analytical acceptance criteria, automated sample preparation, sample analysis
      platforms, data processing and data reporting. 

PMID- 23862711
TI  - Improving productivity and profitability of a bioanalytical business through
      sales and operation planning.
AB  - Today's bioanalytical CROs face increasing global competition, highly variable
      demand, high fixed costs, pricing pressure, and increasing demand for quality and
      speed. Most bioanalytical laboratories have responded to these challenges by
      implementing automation and by implementing process improvement methodologies
      (e.g., Six Sigma). These solutions have not resulted in a significant improvement
      in productivity and profitability since none of them are able to predict the
      upturn or downturn in demand. High volatility of demand causes long lead times
      and high costs during peak demand and poor productivity during trough demand.
      Most bioanalytical laboratories lack the tools to align supply efficiently to
      meet changing demand. In this paper, sales and operation planning (S&OP) has been
      investigated as a tool to balance supply and demand. The S&OP process, when
      executed effectively, can be the single greatest determinant of profitability for
      a bioanalytical business. 

PMID- 23862713
TI  - Risk control and food safety. Foreword.

PMID- 23862714
TI  - Hepatoprotective effects of cod liver oil against sodium nitrite toxicity in
      rats.
AB  - CONTEXT: Exposure to high levels of nitrites for a prolonged time have adverse
      health effects on several organs especially the liver due to oxidative
      properties. Meanwhile, cod liver oil has been reported to ameliorate organ
      dysfunction in animal models that involve oxidative stress. OBJECTIVE: Examine
      the impact of dietary cod liver oil on sodium nitrite-induced liver damage.
      MATERIALS AND METHODS: Thirty-two adult male Sprague-Dawely rats were daily
      treated with sodium nitrite (80 mg/kg) in presence or absence of cod liver oil (5
      ml/kg). Morphological changes were assessed in liver sections. Oxidative stress
      and antioxidant markers were measured in serum and liver homogenates. Liver
      samples were used for measurements of MCP-1, DNA fragmentation and mitochondrial
      function. RESULTS: The hepatoprotective effect of cod liver oil was proved by
      significant reduction of elevated liver enzymes and normal appearance of
      hepatocytes. Cod liver oil significantly reduced hepatic malondialdehyde,
      hydrogen peroxide and superoxide anion (224.3 +/- 18.9 nmol/g, 59.3 +/- 5.1 and
      62.5 +/- 5.1 umol/g, respectively) compared with sodium nitrite (332.5 +/- 25.5
      nmol/g, 83.1 +/- 8.1 and 93.9 +/- 6.5 umol/g, respectively). Cod liver oil
      restored hepatic cytochrome c oxidase activity after 38% reduction by sodium
      nitrite. Furthermore, cod liver oil significantly reduced hepatic MCP-1 (79.8
      pg/mg) and DNA fragmentation (13.8%) compared with sodium nitrite (168.7 pg/mg
      and 41.3%, respectively). DISCUSSION AND CONCLUSION: Cod liver oil ameliorates
      sodium nitrite induced hepatic impairment through several mechanisms including
      attenuation of oxidative stress, blocking MCP-1, reactivation of mitochondrial
      function and reduction of DNA fragmentation.

PMID- 23862715
TI  - Randomized clinical trial on the efficacy and safety of four professional at-home
      tooth whitening gels.
AB  - OBJECTIVE: This randomized clinical trial evaluated the efficacy and safety of
      four gels of differing concentrations used for at-home vital bleaching. MATERIALS
      AND METHODS: Ninety-six volunteers participated in the study and were divided
      into four groups of 24 individuals. A gel of differing concentration was used for
      each group: 10% and 15% carbamide peroxide and 7.5% and 9.5% hydrogen peroxide.
      The patients used the whitening agent in a tray without reservoirs for one hour
      per day for two weeks. The measurement of the change in tooth color was made by
      two observers in the maxillary right central incisor and with a colorimeter in
      both upper central incisors and canines, using the CIE L*a*b* and CIE L*C*h*
      values. Sensitivity was evaluated by the participants on a scale with values as
      follows: 0 = absent, 1 = minor, 2 = moderate, 3 = considerable, 4 = severe.
      RESULTS: At the baseline, the observers noted darker colors than the colorimeter
      (p<0.01), and there were differences between incisors and canines in all the CIE
      L*a*b* and CIE L*C*h* values (p<0.001). In all of the groups and for all of the
      CIE L*a*b* and CIE L*C*h* parameters, there were color changes in the assessments
      made in the four maxillary teeth after treatment (p<0.001). There were no
      differences in DeltaL* and DeltaE* between the groups. The number of patients who
      experienced sensitivity and the intensity of the sensitivity were not
      significant. CONCLUSIONS: There were no differences in the degree of whitening
      among the different products. With all of the products there was an increase in
      L*, a decrease in chromatic intensity (C*), and an increase in the value (tone)
      or hue (h*).

PMID- 23862716
TI  - Recent advances in gene therapy of endometriosis.
AB  - Endometriosis is a gynecological disease that affects up to 10%-15% of all
      reproductive-age women worldwide. It is characterized by the presence of
      endometrial tissues outside the uterine cavity. Endometriosis is a complex
      disease; its pathogenesis includes altered steroid metabolism and immune system
      abnormalities such as inflammation, increased angiogenic activity in the
      peritoneal fluid and impaired recognition of ectopic endometrial cells. The
      development of endometriosis also depends on genetic, anatomical and
      environmental factors. Numerous surgical and medical approaches to treat
      endometriosis have been developed to date. However, complete resolution of the
      problem has not been achieved so far. Gene therapy holds exciting promise for the
      treatment of numerous disorders and current studies have indicated it can also be
      applied to endometriosis. The focus of this review is to summarize the
      pathogenetic background of the disease and to highlight current gene therapy
      approaches for this common gynecological disorder. 

PMID- 23862717
TI  - Functional genome-wide analysis: a technical review, its developments and its
      relevance to cancer research.
AB  - A technique has emerged over the past decade combining chromatin
      immunoprecipitation with DNA microarray analysis. This is a powerful and
      sensitive strategy that has been used extensively to characterise protein
      interactions with chromatin and epigenetic changes such as acetylation and
      methylation throughout the genome of different organisms. This technique has
      revolutionised our understanding of molecular genomics, continues to be widely
      used and is currently being applied in novel areas of cancer research. In this
      publication we review the historical context of this technology and offer current
      and future perspectives on how this technique is currently being developed and
      modified to allow its use in novel areas of research. We discuss the potential
      for this technique and its ongoing important role in biological research
      particularly in relation to cancer research. We also offer insight into the
      potential clinical application of this technology in stratified medicine,
      particularly in the field of cancer therapy.

PMID- 23862719
TI  - Ruthenium-catalyzed carbonylative C-H cyclization of 2-arylphenols: a novel
      synthetic route to 6H-dibenzo[b,d]pyran-6-ones.
AB  - Catalytic carbonylative C-H cyclization of 2-arylphenols can be achieved in the
      presence of a ruthenium-based catalytic system. The process proceeds efficiently
      under balloon pressure of CO and produces variously substituted 6H
      dibenzo[b,d]pyran-6-one compounds, typically in good to high yields. Functional
      groups such as the alkoxycarbonyl and acetyl groups as well as halogen atoms (F,
      Cl, and Br) are well tolerated during the reaction. 

PMID- 23862718
TI  - Cereblon expression in multiple myeloma: not ready for prime time.

PMID- 23862720
TI  - Click chemistry inspired synthesis of glycoporphyrin dendrimers.
AB  - A series of porphyrin-cored glycodendrimers containing 8, 12, 16, and 24 beta-D
      glucopyranose units at the periphery, have been synthesized by convergent
      methodology using click chemistry. The structure of developed dendrimers is
      established by (1)H and (13)C NMR, IR, MALDI-TOF MS, and SEC analysis. Absorption
      emission behavior of dendrimers and its modulation under the influence of the
      dendritic environment is also investigated.

PMID- 23862721
TI  - Discovery of hydroxylated polychlorinated biphenyls (OH-PCBs) in sediment from a
      lake Michigan waterway and original commercial aroclors.
AB  - Hydroxylated polychlorinated biphenyls (OH-PCBs) were measured in surficial
      sediment from Indiana Harbor and Ship Canal (IHSC), East Chicago, IN and five
      original Monsanto Aroclors. These compounds were measured using gas
      chromatography with tandem mass spectrometry (GC-MS/MS) and certified standards
      that allowed us to identify 65 individual or coeluting congeners. Concentrations
      in the sediment ranged from 0.20 to 26 ng/g dry weight. Profiles of most samples
      were similar and were dominated by mono- to penta-chlorinated OH-PCBs.
      Interestingly, most of the samples strongly resembled the OH-PCB profiles of
      Aroclors 1221, 1242, 1248, and 1254, yet 25% of OH-PCBs measured in the sediment
      were not detected in Aroclors. A strong positive correlation was found between
      SigmaOH-PCB and SigmaPCB (p < 0.0001) and also between many individual OH-PCB:PCB
      pairs (p < 0.05). Analysis of OH-PCB:PCB pairs suggest PCB degradation is
      unlikely as a source of OH-PCBs in IHSC sediment. We are the first to report
      levels of OH-PCBs in sediment and Aroclors, and our discovery is significant
      because it is likely that OH-PCB contamination exists in sediment anywhere that
      PCB contamination from Aroclors is present. 

PMID- 23862722
TI  - Shift from covalent to ionic bonding in Al2MoO(y) (y = 2-4) anion and neutral
      clusters.
AB  - The electronic and molecular structures of Al2MoO(y) (y = 2-4) anion and neutral
      complexes were studied using anion photoelectron spectroscopy and density
      functional theory calculations. The spectra are broad, reflecting significant
      structural changes in the transition from anion to neutral, and the neutral
      electron affinities determined from the spectra are similar for all three
      species. The calculations suggest that the lowest energy isomers of the neutral
      clusters can be described as predominantly (Al(+))2[MoO(y)(-2)] ionic complexes,
      in which the Al(+) cations bond with O(2-) anions in a way that minimizes
      repulsion with the positively charged Mo center. The anion structures for all
      three complexes favor closer Mo-Al and Al-Al internuclear distances, with the
      extra negative charge distributed more evenly among all three metal centers.
      Energetically, the fully occupied 3s orbitals on the Al centers are lower than
      the Mo-local 4d-like orbitals and above the O-local 2p-like orbitals. In the case
      of Al2MoO2(-), there is direct Al-Al covalent bonding. The calculated
      spectroscopic parameters for these species are consistent with the observed
      spectra, though definitive assignments are not possible due to the broad,
      unresolved spectra observed and predicted.

PMID- 23862723
TI  - Microparticles prepared from sulfenamide-based polymers.
AB  - Polysulfenamides (PSN), with a SN linkage (RSNR2) along the polymer backbone, are
      a new class of biodegradable and biocompatible polymers. These polymers were
      unknown prior to 2012 when their synthesis and medicinally relevant properties
      were reported. The aim of this study was to develop microparticles as a
      controlled drug delivery system using polysulfenamide as the matrix material. The
      microparticles were prepared by a water-in-oil-in-water double-emulsion solvent
      evaporation method. For producing drug-loaded particles, FITC-dextran was used as
      a model hydrophilic compound. At the optimal formulation conditions, the external
      morphology of the PSN microparticles was examined by scanning electron microscopy
      to show the formation of smooth-surfaced spherical particles with low
      polydispersity. The microparticles had a net negative surface charge (-23 mV) as
      analyzed by the zetasizer. The drug encapsulation efficiency of the particles and
      the drug loading were found to be dependent on the drug molecular weight, amount
      of FITC-dextran used in fabricating FITC-dextran-loaded microparticles,
      concentration of PSN and surfactant, and volume of the internal and external
      water phases. FITC-dextran was found to be distributed throughout the PSN
      microparticles and was released in an initial burst followed by more continuous
      release over time. Confocal laser scanning microscopy was used to qualitatively
      observe the cellular uptake of PSN microparticles and indicated localization of
      the particles in both the cytoplasm and the nucleus.

PMID- 23862724
TI  - Cytotoxicity and in vitro characterization studies of synthesized Jeffamine-cored
      PAMAM dendrimers.
AB  - The objective of this study is to make comprehensive cytotoxicity evaluation and
      in vitro characterization of Jeffamine-cored polyamidoamine (PAMAM) dendrimers on
      L929 cell lines for oral drug delivery purposes. Ester-, amine- and carboxylic
      acid-terminated PAMAMs were investigated for their cytotoxicity on L929 cells at
      different generations and concentrations. Cationic surface charge caused highest
      cytotoxicity on L929 cells, while ester-terminated PAMAMs showed generation- and
      concentration-dependent toxicity. Anionic dendrimers were determined as the
      lowest cytotoxic group, and highest generation number presented lowest cellular
      toxicity. Encapsulation studies were performed with anionic PAMAMs at 2.5, 3.5
      and 4.5 generations and different concentrations. Increasing generation number
      provides greater loaded naproxen amounts and larger particle size. Moreover,
      formulations provide controlled release at simulated terminal ileum conditions.
      Consequently, Jeffamine-cored carboxylic acid-terminated PAMAMs can be a
      promising option for oral drug delivery of poorly water-soluble drugs.

PMID- 23862725
TI  - Horseradish peroxidase-mediated encapsulation of mammalian cells in hydrogel
      particles by dropping.
AB  - We report a method for preparation of mammalian cell-enclosing hydrogel particles
      through horseradish peroxidase (HRP)-catalysed hydrogelation by dropping cell
      suspending aqueous solution into an aqueous coagulation solution. An aqueous
      solution of 10% (w/v) gelatin derivative possessing phenolic hydroxyl (Ph)
      moieties (Gelatin-Ph), HepG2 cells and 10 U/mL HRP was dropped into an aqueous
      coagulation solution containing 1 mM H2O2. The resultant hydrogel formed through
      the HRP-catalysed reaction consuming H2O2 had a spherical shape. The sphericity
      decreased with decreasing concentrations of Gelatin-Ph, HRP and H2O2. The
      thickness of the hydrogel membrane layer of the hydrogel particles could be
      controlled by altering incubation time in the H2O2 solution. The cells
      encapsulated in the particles with a thinner hydrogel membrane grew faster. These
      results demonstrate that we successfully established the method of cell
      encapsulation in hydrogel particles based on dropping aqueous polymer solution
      into aqueous coagulation solution through HRP-catalysed reaction.

PMID- 23862726
TI  - Novel PLA microspheres with hydrophilic and bioadhesive surfaces for the
      controlled delivery of fenretinide.
AB  - Novel polylactide (PLA) microspheres endowed with hydrophilic and bioadhesive
      surfaces as injectable formulations for the controlled release of fenretinide
      were prepared, using a novel technique based on the co-precipitation of PLA with
      gelatin, at the interface of a liquid dispersion formed by the addition of N
      methylpyrrolidone containing PLA and dextrin (DX), towards an aqueous solution of
      gelatin (G). The resulting PLA-G-DX microspheres were compared with others
      prepared by the same technique using polylactide-co-glycolide (PLGA), with or
      without DX, and with or without phosphatidylcholine. Of the different systems,
      the PLA-G-DX microspheres had the best morphological, dimensional and functional
      characteristics. They had the highest drug loading, and their drug release was
      the most efficient over time without any burst effect. Their in vitro anti
      tumoural activity was strongly enhanced with respect to the pure fenretinide.
      This paralleled the increased drug concentration inside the cells due to their
      marked bioadhesion to the tumour cell membranes as indicated by scanning electron
      microscope images.

PMID- 23862727
TI  - Psychrotrophic Streptomyces spp. cells immobilisation in alginate microspheres
      produced by emulsification-internal gelation.
AB  - The objective of the investigations was the optimisation of the parameters for
      cold-adapted Streptomyces MIUG 4 Alga strain cells immobilisation using
      emulsification-internal gelation technique in calcium alginate microspheres and
      testing their ability to produce cold-active beta-amylase. By Box-Behnken design
      and response surface methodology, the effects of independent variables were
      established, which included sodium alginate concentration (A), sodium
      alginate:living cell ratio (B) and the Span 80 concentration (C) upon
      microspheres formation and their functionality. Mean diameter of formed
      microspheres with immobilised biomass and cold-active beta-amylase production
      were chosen as dependent variables in order to increase the yield of starch
      hydrolysis. Diameters of microspheres <25.5 MUm provided large yield of cold
      active beta-amylase comparing with microspheres with bigger diameter. A 1.5-fold
      increase in the substrate hydrolysis yield was achieved using the immobilised
      biocatalyst compared with the crude enzyme extract, after 96 h of substrate
      bioconversion.

PMID- 23862729
TI  - Daily polyphenol intake from fresh fruits in Portugal: contribution from berry
      fruits.
AB  - Fresh fruits, particularly berries, are rich in polyphenols. These bioactive
      compounds are important in the prevention of chronic inflammatory diseases. The
      present study aimed to assess polyphenol intake from fresh fruit in Portugal and
      the relative contribution of berries to overall intake, using an online semi
      quantitative food frequency questionnaire. Consumption of processed berry
      products was also studied. Mean fresh fruit consumption was 365.6 +/- 8.2 g/day.
      Berries accounted for 9% of total fresh fruit intake, from which 80% were due to
      strawberries. Total polyphenol intake from fresh fruits was 783.9 +/- 31.7 mg of
      Gallic Acid Equivalents (GAE) per day, from which 14% were from berries. Within
      berries, strawberries accounted for 11% of total polyphenol intake, with the
      other consumed berries accounting for 3% of the total polyphenol intake per day.
      Main reasons reported for relative low consumption of berries were market
      availability and price. The most consumed processed berry product was yogurt.

PMID- 23862730
TI  - Laboratory intercomparison of the dicentric chromosome analysis assay.
AB  - The study design and obtained results represent an intercomparison of various
      laboratories performing dose assessment using the dicentric chromosome analysis
      (DCA) as a diagnostic triage tool for individual radiation dose assessment.
      Homogenously X-irradiated (240 kVp, 1 Gy/min) blood samples for establishing
      calibration data (0.25-5 Gy) as well as blind samples (0.1-6.4 Gy) were sent to
      the participants. DCA was performed according to established protocols. The time
      taken to report dose estimates was documented for each laboratory. Additional
      information concerning laboratory organization/characteristics as well as assay
      performance was collected. The mean absolute difference (MAD) was calculated and
      radiation doses were merged into four triage categories reflecting clinical
      aspects to calculate accuracy, sensitivity and specificity. The earliest report
      time was 2.4 days after sample arrival. DCA dose estimates were reported with
      high and comparable accuracy, with MAD values ranging between 0.16-0.5 Gy for
      both manual and automated scoring. No significant differences were found for dose
      estimates based either on 20, 30, 40 or 50 cells, suggesting that the scored
      number of cells can be reduced from 50 to 20 without loss of precision of triage
      dose estimates, at least for homogenous exposure scenarios. Triage categories of
      clinical significance could be discriminated efficiently using both scoring
      procedures. 

PMID- 23862732
TI  - Accuracy of angle and position of the cup using computed tomography-based
      navigation systems in total hip arthroplasty.
AB  - OBJECTIVE: The objectives of this study were to evaluate the accuracy of computed
      tomography (CT)-based navigation and to investigate whether the level of surgeon
      experience affects the accuracy of cup positioning under navigation. METHODS:
      This study investigated 117 hips in 103 patients who underwent primary total hip
      arthroplasty (THA) by 7 surgeons using a CT-based navigation system. Pre- and
      postoperative CT images were matched using a volume registration technique.
      Postoperative cup angles and positions were then measured using the same pelvic
      coordinates, and results were compared for experienced and inexperienced
      surgeons. RESULTS: The mean absolute error of the cup angle was 1.8 +/- 1.6
      degrees  for inclination and 1.2 +/- 1.1 degrees  for anteversion. The mean
      absolute errors of cup position were 1.9 +/- 1.5 mm, 1.4 +/- 1.2 mm, and 1.9 +/-
      1.3 mm on the x-, y- and z-axes, respectively. No significant differences in
      accuracy were identified between experienced and inexperienced surgeons.
      CONCLUSIONS: The absolute spatial error of cup position was <= 2 mm for each
      axis, and the angle error was <= 2 degrees  for the angles of inclination and
      anteversion. This navigation system could therefore help surgeons perform
      accurate cup placement irrespective of the surgeon's level of experience.

PMID- 23862733
TI  - Accelerated conformational entropy calculations using graphic processing units.
AB  - Conformational entropy calculation, usually computed by normal-mode analysis
      (NMA) or quasi harmonic analysis (QHA), is extremely time-consuming. Here,
      instead of NMA or QHA, a solvent accessible surface area (SASA) based model was
      employed to compute the conformational entropy, and a new fast GPU-based method
      called MURCIA (Molecular Unburied Rapid Calculation of Individual Areas) was
      implemented to accelerate the calculation of SASA for each atom. MURCIA employs
      two different kernels to determine the neighbors of each atom. The first kernel
      (K1) uses brute force for the calculation of the neighbors of atoms, while the
      second one (K2) uses an advanced algorithm involving hardware interpolations via
      GPU texture memory unit for such purpose. These two kernels yield very similar
      results. Each kernel has its own advantages depending on the protein size. K1
      performs better than K2 when the size is small and vice versa. The algorithm was
      extensively evaluated for four protein data sets and achieves good results for
      all of them. This GPU-accelerated version is ~600 times faster than the former
      sequential algorithm when the number of the atoms in a protein is up to 105.

PMID- 23862731
TI  - Laboratory intercomparison of the cytokinesis-block micronucleus assay.
AB  - The focus of the study is an intercomparison of laboratories' dose-assessment
      performances using the cytokinesis-block micronucleus (CBMN) assay as a
      diagnostic triage tool for individual radiation dose assessment. Homogenously X
      irradiated (240 kVp, 1 Gy/min) blood samples for establishing calibration data
      (0.25-5 Gy) as well as blind samples (0.1-6.4 Gy) were sent to the participants.
      The CBMN assay was performed according to protocols individually established and
      varying among participating laboratories. The time taken to report dose estimates
      was documented for each laboratory. Additional information concerning laboratory
      organization/characteristics as well as assay performance was collected. The mean
      absolute difference (MAD) was calculated and radiation doses were merged into
      four triage categories reflecting clinical aspects to calculate accuracy,
      sensitivity and specificity. The earliest report time was 4 days after sample
      arrival. The CBMN dose estimates were reported with high accuracy (MAD values of
      0.20-0.50 Gy at doses below 6.4 Gy for both manual and automated scoring
      procedures), but showed a limitation of the assay at the dose point of 6.4 Gy,
      which resulted in a clear dose underestimation in all cases. The MAD values
      (without 6.4 Gy) differed significantly (P = 0.03) between manual (0.25 Gy, SEM =
      0.06, n = 4) or automated scoring procedures (0.37 Gy, SEM = 0.08, n = 5), but
      lowest MAD were equal (0.2 Gy) for both scoring procedures. Likewise, both
      scoring procedures led to the same allocation of dose estimates to triage
      categories of clinical significance (about 83% accuracy and up to 100%
      specificity). 

PMID- 23862735
TI  - Attitudes toward placentophagy: a brief report.
AB  - Placentophagy is the consumption of the placenta after birth. For the present
      study, an online survey explored knowledge and attitudes toward the practice.
      Participants (N = 216, 78.7% female, 19.9% male) completed Internet-based surveys
      on placentophagy. A majority (66%) had heard about placentophagy, and of these,
      23.1% had learned about the practice through the media. A small number of
      participants (3.3%) had eaten human placental tissue. Male and female respondents
      did not differ in willingness to eat placenta (chi (2)(2) = 1.60, p = .45).
      Contrary to popular belief, placentophagy appears to be rare in human history and
      across cultures. Future research should explore changing attitudes toward
      placentophagy across cultures. 

PMID- 23862734
TI  - Cofilin-induced changes in F-actin detected via cross-linking with benzophenone-4
      maleimide.
AB  - Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family of
      proteins. It plays a key role in actin dynamics by promoting disassembly and
      assembly of actin filaments. Upon its binding, cofilin has been shown to bridge
      two adjacent protomers in filamentous actin (F-actin) and promote the
      displacement and disordering of subdomain 2 of actin. Here, we present evidence
      for cofilin promoting a new structural change in the actin filament, as detected
      via a switch in cross-linking sites. Benzophenone-4-maleimide, which normally
      forms intramolecular cross-linking in F-actin, cross-links F-actin
      intermolecularly upon cofilin binding. We mapped the cross-linking sites and
      found that in the absence of cofilin intramolecular cross-linking occurred
      between residues Cys374 and Asp11. In contrast, cofilin shifts the cross-linking
      by this reagent to intermolecular, between residue Cys374, located within
      subdomain 1 of the upper protomer, and Met44, located in subdomain 2 of the lower
      protomer. The intermolecular cross-linking of F-actin slows the rate of cofilin
      dissociation from the filaments and decreases the effect of ionic strength on
      cofilin-actin binding. These results are consistent with a significant role of
      filament flexibility in cofilin-actin interactions. 

PMID- 23862736
TI  - Dietary exposure of Hong Kong adults to fatty acid esters of 3-monochloropropane
      1,2-diol.
AB  - A total of 290 individual food samples were collected in Hong Kong, China, for 3
      monochloropropane-1,2-diol (3-MCPD) fatty acid esters analysis. Most samples were
      processed food and in ready-to-eat form. The results show that the levels of 3
      MCPD fatty acid esters were high in biscuits, fats and oils, snacks and Chinese
      pastry with mean bound 3-MCPD levels of 440, 390, 270 and 270 MUg kg-1,
      respectively. The dietary exposures to bound 3-MCPD of average and high adult
      consumers were estimated to be 0.20 and 0.53 MUg kg bw-1 day-1, respectively. The
      primary toxicological concern of 3-MCPD fatty acid esters is its potential to
      release 3-MCPD in vivo during digestion in the gastrointestinal tract. 3-MCPD
      would affect the kidney, the central nervous system and the male reproductive
      system of rats. Assuming that 100% of the 3-MCPD was released from 3-MCPD fatty
      acid esters by hydrolysis in the digestive system, the dietary exposures to 3
      MCPD for average and high adult consumers were only 10% and 26% of the
      provisional maximum tolerable daily intake (PMTDI) of 3-MCPD established by the
      Joint Food and Agriculture Organization/World Health Organization Expert
      Committee on Food Additives (JECFA) (2 MUg kg bw-1 day-1), respectively. The
      results suggest that both average and high adult consumers are unlikely to
      experience major toxicological effects of 3-MCPD.

PMID- 23862737
TI  - Bowman-Birk inhibitor-like protein is secreted by sprouted pea seeds in response
      to induced colonization by enteropathogenic Escherichia coli.
AB  - The interaction between the clinical isolate of enteropathogenic Escherichia coli
      (EPEC) SBANU8 and pea sprouts was compared with avirulent K 12. E. coli. This was
      carried out by repeated co-incubation with pea sprouts for 5 days, and the
      protein profile of the culture supernatant was analyzed by single and two
      dimensional electrophoresis. Mass spectrometry analysis led to the identification
      of two serine protease inhibitors including a Bowman-Birk-type protein secreted
      by pea sprouts in response to clinical isolate. Expression of the E. coli intimin
      gene involved in animal host colonization and virulence was studied by reverse
      transcription polymerase chain reaction. Expression of this gene was high in
      SBANU8 when co-incubated with pea sprouts. The present study gives baseline data
      on the molecular level interactions of EPEC and pea sprouts, which are needed to
      design the outbreak control strategies.

PMID- 23862739
TI  - Counselling against HIV in Africa: a genealogy of confessional technologies.
AB  - This paper contextualises counselling within a broader historical formation that
      links disclosure to healing and deploys confessional technologies to incite
      disclosure and awareness of the mysterious substance of the self. Foucault's
      argument that sexuality was the privileged arena for using confessional
      technologies to 'produce' the truth of the self is particularly relevant in light
      of the diffusion of counselling practices in Africa in the wake of the HIV
      epidemic, particularly with their emphasis on inciting appropriate sexual
      behaviour. Examination of the historical assemblage of counselling practices
      shows how they articulate what the self is, the nature of truth and a politics of
      language. This paper focuses on the genealogy of four key assumptions that
      express this confessional reason. These are that: (1) people can be 'empowered'
      to have control on their own lives by working on themselves, (2) secrets untold
      become pathogens, (3) the ability to heal requires that one first overcome
      personal illness, (4) the experience of sharing secrets is cathartic and healing.
      The genealogy intertwines four strands: that of the Unconscious as revealed by
      Freud and his followers, attempts to treat shell-shocked veterans of World War I,
      group psychotherapy and participatory research after World War II. 

PMID- 23862738
TI  - Impact of blood glucose variability on carotid artery intima media thickness and
      distensibility in type 1 diabetes mellitus.
AB  - AIMS: Diabetes mellitus is characterized by structural and functional alterations
      of the large- and medium-size arteries. Whether blood glucose variability, i.e.
      the glycemic oscillations occurring during the 24-h period, represents a risk
      factor for vascular alterations additional to and independent on HbA1c in type 1
      diabetes mellitus is still undefined. The present study was carried out with the
      aim at investigating the impact of different measures of blood glucose
      variability on arterial structure and function. We studied 17 non-complicated
      type 1 diabetic patients (11 males, six females) with an age of 40.8 +/- 7.6
      years (mean +/- SD). In each patient, 24-h glucose profile was obtained by
      continuous glucose monitoring system and glucose variability was expressed as
      mean +/- SD of 24-h blood glucose levels, mean amplitude of glycemic excursions
      and postprandial hyperglycemic spikes. Arterial structure and function was
      measured as carotid IMT and stiffness. MAJOR FINDINGS: The different approaches
      to assessing blood glucose variability well correlated between and with HbA1c.
      Carotid IMT and stiffness showed significant correlations with age, blood
      pressure, heart rate and daily insulin intake but a non- significant correlation
      with blood glucose variability. PRINCIPAL CONCLUSION: Thus, in type 1 diabetes
      mellitus, measures of glycemic variability are useful in predicting both actual
      and long-lasting glycemic control. In absence of diabetes-related complications
      and of any intima-media thickness alterations, the major predictors of arterial
      distensibility are represented by traditional risk factors beside glycemic 24-h
      control.

PMID- 23862740
TI  - Cross-cultural emotional prosody recognition: evidence from Chinese and British
      listeners.
AB  - This cross-cultural study of emotional tone of voice recognition tests the in
      group advantage hypothesis (Elfenbein & Ambady, 2002) employing a quasi-balanced
      design. Individuals of Chinese and British background were asked to recognise
      pseudosentences produced by Chinese and British native speakers, displaying one
      of seven emotions (anger, disgust, fear, happy, neutral tone of voice, sad, and
      surprise). Findings reveal that emotional displays were recognised at rates
      higher than predicted by chance; however, members of each cultural group were
      more accurate in recognising the displays communicated by a member of their own
      cultural group than a member of the other cultural group. Moreover, the
      evaluation of error matrices indicates that both culture groups relied on similar
      mechanism when recognising emotional displays from the voice. Overall, the study
      reveals evidence for both universal and culture-specific principles in vocal
      emotion recognition. 

PMID- 23862741
TI  - The role of Act1, a NF-kappaB-activating protein, in IL-6 and IL-8 levels induced
      by IL-17 stimulation in SW982 cells.
AB  - CONTEXT: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized
      by chronic inflammation in the synovial membrane of affected joints. It has been
      shown that several kinds of cytokine were increased in synovial fluid, while the
      underlying mechanism remains poorly understood. OBJECTIVES: NF-kappaB activator 1
      (Act1) is a recently identified protein binding to the IkappaB kinase complex.
      Our study aimed to investigate the expression of Act1 induced by cytokine IL-17
      stimulation in SW982 cells. MATERIALS AND METHODS: The human synovial sarcoma
      cell line SW982 and primary cultured RA fibroblast-like synovial cells were used.
      RT-PCR and Western blot assays were selected to investigate the genetic and
      protein expression of Act1. Additionally, four independent Act1 small interfering
      RNA (siRNA) oligonucleotides were designed and obtained according to the GenBank
      cDNA, the sequence of Act1 (Traf3ip2). Finally, enzyme-linked immunosorbent assay
      (ELISA) double antibody sandwich was used to assay supernatant IL-6 and IL-8
      concentrations. RESULTS: The Act1 mRNA expression level increased significantly
      after stimulation with IL-17 (5-100 ng/ml) in SW982 cells. Additionally, the
      level of Act1 mRNA expression correlated positively with the concentration of IL
      17 (p < 0.01). IL-17 induced IL-6 and IL-8 in SW982 cells was in a concentration-
      and time-dependent way. Furthermore, ELISA assay revealed that IL-17 (20 ng/ml)
      significantly increased IL-6 (1927.4 +/- 288.77 versus 786.5 +/- 172.42 ng/ml, p
      < 0.01) and IL-8 levels (984.8 +/- 95.09 ng/ml versus 307.1 +/- 90.83 ng/ml, p <
      0.01) compared with control group after stimulation for 24 h. However,
      transfection of Traf3ip2 siRNA markedly decreased IL-6 (995.9 +/- 115.30 ng/ml
      versus 1816.1 +/- 273.27 ng/ml, p < 0.01) and IL-8 levels (575.6 +/- 65.96 ng/ml
      versus 929.4 +/- 124.39 ng/ml, p < 0.01) compared to transfection negative
      control. These findings suggested that IL-6 and IL-8 level induced by IL-17 in
      SW982 cells could be reversed by down-regulation of Act1 expression level with
      Traf3ip2 siRNA. CONCLUSION: Our results suggested that Act1 might play a key role
      in the pathophysiology and the treatment of RA.

PMID- 23862742
TI  - Double minutes with MYC amplification in a patient with chronic myelomonocytic
      leukaemia transformed into acute myeloid leukaemia.

PMID- 23862743
TI  - Evaluating radiation-induced white matter changes in patients treated with
      stereotactic radiosurgery using diffusion tensor imaging: a pilot study.
AB  - Stereotactic radiosurgery (SRS) has been an effective treatment method for brain
      tumors; however, few data are available regarding radiation-induced white matter
      (WM) damage by SRS. In this work, diffusion tensor imaging (DTI) was used to
      investigate WM changes following SRS. Fifteen patients with gliomas were
      enrolled, with prescription doses ranging 18-25 Gy. Patients were scanned with
      magnetic resonance imaging (MRI) including DTI before and after SRS. Diffusion
      tensors were calculated and fiber tracking was performed. Non-irradiated WM
      volumes and irradiated WM volumes receiving >= 12 Gy and >= Gy were contoured as
      volumes of interest (VOI). Apparent diffusion coefficient (<D>), fractional
      anisotropy (FA) and number of fibers (NF) were calculated and assessed using the
      Wilcoxon signed-rank test. Compared with those of non-irradiated VOIs, FA and NF
      decreased considerably after two months of SRS in the irradiated WM VOIs. The
      variation in (<D> was however small and was not statistically significant. The
      preliminary results suggested that FA and NF might potentially be more sensitive
      indicators than (<D> in measuring radiation-induced WM changes and DTI could be a
      valuable tool to assess radiation-induced WM changes in SRS. Although it is still
      preliminary, this pilot study may be useful to provide insights for future
      studies. 

PMID- 23862744
TI  - Treatment and technical intervention time analysis of a robotic stereotactic
      radiotherapy system.
AB  - The purpose of this study is to obtain a better operational knowledge of
      Stereotactic Body Radiotherapy (SBRT) treatments with CyberKnife(r). An analysis
      of both In-room Times (IRT) and technical interventions of 5 years of treatments
      was performed, during which more than 1600 patients were treated for various
      indications, including liver (21%), lung (29%), intracranial (13%), head and neck
      (11%) and prostate (7%). Technical interventions were recorded along with the
      time of the failure, time to the intervention, and the complexity and duration of
      the repair. Analyses of Time Between Failures (TBF) and Service Disrupting
      TBF(disr) were performed. Treatment time data and variability per indication and
      following different system upgrades were evaluated. Large variations of IRTs were
      found between indications, but also large variations for each indication. The
      combination of the time reduction Tool (using Iris(r)) and Improved Stop Handling
      was of major impact to shortening of treatment times. The first implementation of
      the Iris collimator alone did not lead to significantly shorter IRTs for us
      except during prostate treatments. This was mostly due to the addition at the
      same time of larger rotational compensation for prostate treatments (58 instead
      of 1.58). Significant differences of duration between the first fraction and
      following fractions of a treatment, representing the necessity of defining
      imaging parameters and explanation to patients, were found for liver (12 min) and
      lung treatments using Xsight(r) Spine (5 min). Liver and lung treatments
      represent the longest IRT's and involve the largest variability's in IRT. The
      malfunction rate of the system followed a Weibull distribution with the shape and
      scale parameters of 0.8 and 39.7. Mean TBF(disr) was 68 work hours. 60 to 80% of
      the service disrupting interventions were resolved within 30-60 min, 5% required
      external intervention and 30% occurred in the morning. The presented results can
      be applied in the evaluation of the required machine time in order to implement
      robotic radiosurgery for different indications. The analytical distributions of
      IRTs and technical interruptions can be used for simulations. 

PMID- 23862745
TI  - The value of surface enhanced laser desorption/ionization-time of flight mass
      spectrometry at the diagnosis of non-small cell lung cancer: a systematic review.
AB  - Numbers of studies used surface enhanced laser desorption/ionization-time of
      flight mass spectrometry (SELDI-TOF-MS) to find novel serum biomarkers for non
      small cell lung cancer (NSCLC). It is arguable whether the SELDI technique has
      its value of diagnostic accuracy for NSCLC. The purpose of our study is to
      determine the diagnostic accuracy of SELDI-TOF-MS for diagnosing NSCLC. The
      Cochrane Central Register of Controlled Trials, MEDLINE, Pub Med, EMBASE, the
      Chinese Biomedical Literature Database, the China Academic Journals Full-text
      Database, and the Chinese Scientific Journals Database were searched
      systematically for potential studies. Reference lists of included studies and
      review articles were also reviewed. All studies that reported data on patients
      with a confirmed diagnosis of NSCLC and that compared the measurement of SELDI
      TOF-MS with pathology standard were considered for inclusion. 11 studies were
      included in the systematic review. The ranges of the diagnostic value of SELDI
      TOF-MS for NSCLC were as follows: sensitivity (SEN) was 0.70~1.00; specificity
      (SPE) was 0.68~1.00; positive likelihood ratio (PLR) was 2.23~23.14; negative
      likelihood ratio (NLR) was 0.04~0.43; and diagnostic odds ratio (DOR) was
      5.17~621.0, respectively. SELDI-TOF-MS showed high accuracy in identifying NSCLC,
      and could be a potential screening tool for diagnosing NSCLC patients.

PMID- 23862746
TI  - Acceptance and commissioning of a treatment planning system based on Monte Carlo
      calculations.
AB  - The Monaco Treatment Planning System (TPS), based on a virtual energy fluence
      model of the photon beam head components of the linac and a dose computation
      engine made with Monte Carlo (MC) algorithm X-Ray Voxel MC (XVMC), has been
      tested before being put into clinical use. An Elekta Synergy with 6 MV was
      characterized using routine equipment. After the machine's model was installed, a
      set of functionality, geometric, dosimetric and data transfer tests were
      performed. The dosimetric tests included dose calculations in water,
      heterogeneous phantoms and Intensity Modulated Radiation Therapy (IMRT)
      verifications. Data transfer tests were run for every imaging device, TPS and the
      electronic medical record linked to Monaco. Functionality and geometric tests
      were run properly. Dose calculations in water were in accordance with
      measurements so that, in 95% of cases, differences were up to 1.9%. Dose
      calculation in heterogeneous media showed expected results found in the
      literature. IMRT verification results with an ionization chamber led to dose
      differences lower than 2.5% for points inside a standard gradient. When an 2-D
      array was used, all the fields passed the g (3%, 3 mm) test with a percentage of
      succeeding points between 90% and 95%, of which the majority of the mentioned
      fields had a percentage of succeeding points between 95% and 100%. Data transfer
      caused problems that had to be solved by means of changing our workflow. In
      general, tests led to satisfactory results. Monaco performance complied with
      published international recommendations and scored highly in the dosimetric
      ambit. However, the problems detected when the TPS was put to work together with
      our current equipment showed that this kind of product must be completely
      commissioned, without neglecting data workflow, before treating the first
      patient. 

PMID- 23862747
TI  - Tissue engineering concept in the research of the tumor biology.
AB  - Tumor is a heterogeneous complex, which lives in a three-dimensional environment
      flush with biopathophysiological and biomechanical signals. This signaling
      abundant extracellular milieu co-evolving from cell-cell and cell-host
      interaction guides the development and the generation of the tumor. There has
      been a recent surge of interest in studying the tumor biology that more closely
      mirror what happens in living organisms, especially in cancer research.
      Incorporating cancer cells in the 3D mimicking environment instead of monolayers
      is reasonable for maintaining in vivo cancer behaviors in spatial and temporal
      context. However, 3D culture for cancer still presents a challenge for
      researchers in this field. Tissue engineering, originally aiming at designing the
      artificial organs, provided a feasible approach to recreate such complex
      mechanical and biochemical interplay. Aside from reproducing bionic environment,
      tissue engineering has been routinely introduced into cancer study to build three
      dimensional structures not only to develop molecular therapeutics, but also to
      screen for toxic effects of drugs or radiotherapy sensitivity. In this article,
      we focused on the recent advances of the well-defined tissue-engineering
      biomaterials in the application in tumor biology. We also discussed the
      fabrications of the scaffolds from different materials, which might contribute to
      future cancer research. 

PMID- 23862749
TI  - New polar intermetallic phases RE2Zn5Tt (RE = La-Nd; Tt = Sn and Pb): synthesis,
      structure, chemical bonding, and magnetic properties.
AB  - Reported are the synthesis, crystal structure, electronic structure, and magnetic
      properties of a series of zinc-rich ternary phases with formulas RE2Zn5Tt (RE =
      La-Nd; Tt = Sn and Pb). The structures of these compounds have been established
      by single-crystal and powder X-ray diffraction. They crystallize in the
      orthorhombic space group Cmcm (No. 63, LaRhSn2 structure type, Pearson symbol
      oC32). The most prominent structural feature is the trigonal-planar coordination
      of the Sn(Pb) atoms; the latter interconnect layers of Zn atoms to comprise a
      complex [Zn5Tt] polyanionic framework. The structural relationships between the
      structure of the title compounds and the EuIn4, La3Al11, and YIrGe2 structure
      types are highlighted. Temperature-dependent DC magnetization measurements
      indicate Pauli-like paramagnetism for La2Zn5Sn, while Ce2Zn5Sn, Pr2Zn5Sn, and
      Nd2Zn5Sn display Curie-Weiss behavior in the high-temperature regime. At
      cryogenic temperatures, the magnetic responses of Ce2Zn5Sn, Pr2Zn5Sn, and
      Nd2Zn5Sn appear to deviate from the Curie-Weiss law; however, no magnetic
      orderings could be observed down to 5 K. Theoretical considerations of the
      electronic structure on the basis of the tight-binding linear muffin-tin orbital
      (TB-LMTO-ASA) method are also presented and discussed. 

PMID- 23862748
TI  - MicroRNA-34a targets Bcl-2 and sensitizes human hepatocellular carcinoma cells to
      sorafenib treatment.
AB  - MiR-34a, a direct target of p53, has been shown to target several molecules
      associated with the cell cycle and cell survival pathways, and its dysregulation
      is implicated in cancer drug resistance or sensitivity in several human cancers.
      However, the correlation between miR-34a expression and chemoresistance has not
      been explored in HCC. In this study, we confirmed that miR-34a was significantly
      down-regulated in HCC tissues and HCC cell lines by qRT-PCR. HCC tissues with
      lower miR-34a expression displayed higher expression of Bcl-2 protein than those
      with high expression of miR-34a; therefore, an inverse correlation is evident
      between the miR-34a level and Bcl-2 expression. Moreover, patients with lower miR
      34a expression had significantly poorer overall survival. Bioinformatics and
      luciferase reporter assays revealed that miR-34a binds the 3'-UTR of the Bcl-2
      mRNA and represses its translation. Western blotting analysis and qRT-PCR
      confirmed that Bcl-2 is inhibited by miR-34a overexpression. Functional analyses
      indicated that the restoration of miR-34a reduced cell viability, promoted cell
      apoptosis and potentiated sorafenib-induced apoptosis and toxicity in HCC cell
      lines by inhibiting Bcl-2 expression. This study is the first to demonstrate that
      miR-34a induces sensitivity to the anti-tumor effect of sorafenib in human HCC
      cells, suggesting a potential role of miR-34a in the treatment of HCC. 

PMID- 23862750
TI  - The BRAIN Initiative: toward a chemical connectome.

PMID- 23862751
TI  - Visualizing neurotransmitter secretion at individual synapses.
AB  - To advance understanding of the brain, the ability to measure both nerve cell
      electrical spiking and chemical neurotransmission with high spatial resolution is
      required. In comparison to the development of voltage sensors and Ca(2+)
      indicator dyes over the past several decades, high resolution imaging of
      neurotransmitter (NT) release at single synapses has not been possible. In this
      Viewpoint, we discuss two recent developments toward this goal, namely, the
      design of fluorescent false neurotransmitters (FFNs) and optical neurotransmitter
      sensors. 

PMID- 23862752
TI  - Influence of molecular structure on the laser-induced plasma emission of the
      explosive RDX and organic polymers.
AB  - A series of organic polymers and the military explosive
      cyclotrimethylenetrinitramine (RDX) were studied using the light emission from a
      femtosecond laser-induced plasma under an argon atmosphere. The relationship
      between the molecular structure and plasma emission was established by using the
      percentages of the atomic species (C, H, N, O) and bond types (C-C, C?C, C-N, and
      C=N) in combination with the atomic/molecular emission intensities and decay
      rates. In contrast to previous studies of organic explosives in which C2 was
      primarily formed by recombination, for the organic materials in this study the
      percentage of C-C (and C?C) bonds was strongly correlated to the molecular C2
      emission. Time-resolved emission spectra were collected to determine the
      lifetimes of the atomic and molecular species in the plasma. Observed differences
      in decay rates were attributed to the differences in both the molecular structure
      of the organic polymers or RDX and the chemical reactions that occur within the
      plasma. These differences could potentially be exploited to improve the
      discrimination of explosive residues on organic substrates with laser-induced
      breakdown spectroscopy. 

PMID- 23862753
TI  - Probing isotope shifts in 103Rh and 195Pt NMR spectra with density functional
      theory.
AB  - Zero-point vibrationally averaged (rg(0)) structures were computed at the
      PBE0/SDD/6-31G* level for the [Pt(35)Cln(37)Cl5-n(H2(18)O)](-) (n = 0-5), cis
      Pt(35)Cln(37)Cl4-n(H2(18)O)(H2(16)O) (n = 0-4), fac-[Pt(35)Cln(37)Cl3
      n(H2(18)O)(H2(16)O)2](+) (n = 0-3), [Pt(35)Cln(37)Cl5-n((16/18)OH)](2-) (n = 0
      5), cis-[Pt(35)Cln(37)Cl4-n((16/18)OH)2](2-) (n = 0-4), fac-[Pt(35)Cln(37)Cl3
      n((16/18)OH)3](2-) (n = 0-3), cis-[Pt(35)Cln(37)Cl2-n((16/18)OH)4](2-) (n = 0-2),
      [Pt(35)Cln(37)Cl1-n((16/18)OH)5](2-) (n = 0-1), [Rh(35)Cln(37)Cl5-n(H2O)](2-) (n
      = 0-5), cis-[Rh(35)Cln(37)Cl4-n(H2O)2](-) (n = 0-4), and fac-Rh(35)Cln(37)Cl3
      n(H2O)3 (n = 0-3) isotopologues and isotopomers. Magnetic shielding constants,
      computed at the ZORA-SO/PW91/QZ4P/TZ2P level, were used to evaluate the
      corresponding (35/37)Cl isotope shifts on the (195)Pt and (103)Rh NMR spectra,
      which are known experimentally. While the observed effects are reproduced
      reasonably well computationally in terms of qualitative trends and the overall
      order of magnitude (ca. 1 ppm), quantitative agreement with experiment is not yet
      achieved. Only small changes in M-Cl and M-O bonds upon isotopic substitution, on
      the order of femtometers, are necessary to produce the observed isotope shifts. 

PMID- 23862754
TI  - The development and validation of a short form of the STERLinG: a practical,
      valid and reliable tool to evaluate teacher competencies to encourage reflective
      learning.
AB  - BACKGROUND: To optimize response rates, it is important to have brief,
      comprehensive instruments. AIMS: We have developed and validated a short form of
      an instrument for measuring students' perceptions of teachers' competencies to
      encourage students' reflective learning in small groups (the STERLinG). METHODS:
      Based on statistical and content criteria, the original 36-item STERLinG was
      reduced to 15 items: three scales with five items each. This mini-STERLinG was
      validated. Confirmatory factor analysis was performed and internal consistencies
      were calculated. RESULTS: The instrument was completed by 501 respondents (63%).
      The original instrument structure was confirmed with 62.6% explained variance.
      Reliabilities were high with 0.91 for the entire mini-STERLinG and 0.87, 0.85 and
      0.81 for its subscales. CONCLUSIONS: The mini-STERLinG was found to be a
      feasible, valid and reliable instrument.

PMID- 23862755
TI  - Cationic albumin-conjugated magnetite nanoparticles, novel candidate for
      hyperthermia cancer therapy.
AB  - We developed a novel hyperthermia material for cancer therapy, cationic albumin
      conjugated magnetite nanoparticles (MNPs), which absorb the energy of an
      alternating magnetic field and convert it into heat. MNPs of about 10 nm were
      synthesised through co-precipitation, and citric acid was used to stabilise the
      MNP suspension. Then albumin was cationised by replacing anionic side chain
      groups with cationic groups. The surface modification of the MNPs was provided by
      cationic albumin, which was covalently conjugated to carboxylic acid functions
      located at the distal end of the MNPs' surface by carbodiimide chemistry.
      Finally, we obtained stable superparamagnetic suspensions with particle sizes of
      140 nm and saturation magnetisation of 67 emu/g, which do not have the
      disadvantage of eventual desorption of physical attachment. We also analysed the
      potential of these particles for magnetic fluid hyperthermia by determination of
      the specific absorption rate at a constant frequency of 215 kHz; the temperature
      increase of the particles was 30.8  degrees C. This study experimentally
      demonstrates the high efficiency of these nano-heaters.

PMID- 23862756
TI  - Interleukin-6 and Lung Inflammation: Evidences of A Causing Role in Inducing
      Respiratory System Resistance Increments.
AB  - Interleukin-6 has been shown to be increased in various pathological conditions
      involving the lungs, both experimentally induced in animals, or spontaneously
      occurring in humans. Experimental data demonstrating a significant role of
      interleukin-6 in commonly occurring respiratory system inflammatory diseases are
      reviewed. These diseases, i.e. asthma and chronic obstructive pulmonary disease,
      are characterised by respiratory system mechanical derangement, most of all
      because increased elastance and airway resistance. Recent findings showing a
      causative role of interleukin-6 in determining an airway resistance increment are
      reviewed. By applying the end-inflation occlusion method to study respiratory
      system mechanical properties before and after interleukin-6 administration, it
      was shown that this cytokine induced significant increments in both the resistive
      pressure dissipation due to frictional forces opposing the airflow in the airway
      (ohmic resistance), and in the additional resistive pressure dissipation due to
      the visco-elastic properties of the system, i.e. stress relaxation (visco-elastic
      resistance). A dose-dependent effect was also demonstrated. No effects were
      instead detected on respiratory system elastance. Even solely administrated in
      healthy mammals, interleukin-6 exhibits a significant effect on respiratory
      system resistances, leading to increased inspiratory muscle mechanical work of
      breathing. Thus, IL-6 may play an active role in the pathogenesis of respiratory
      system diseases. The possible involved mechanisms are discussed.

PMID- 23862757
TI  - With the benefit of hindsight: trials using retrospective controls versus
      randomized controlled trials in clinical toxicology.

PMID- 23862758
TI  - Anaphylactoid reactions to N-acetylcysteine.

PMID- 23862759
TI  - Antioxidant and androgenic effects of dietary ginger on reproductive function of
      male diabetic rats.
AB  - This study evaluated the antioxidant and androgenic properties of ginger roots on
      the reproductive function of male diabetic rats. Animals were divided into three
      groups; the control (Control), diabetic (Diab) and diabetic fed with dietary
      ginger for 30 d (Diab + Z). Thereafter, blood samples were collected and
      reproductive organs (testis, epididymis, prostate and seminal vesicle) were
      removed for determination of sperm parameters, malondialdehyde (MDA) level,
      glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), lactate
      dehydrogenase (LDH), alkaline phosphatase (ALP) and aspartate and lactate
      aminotransferase (AST and ALT) activities. Dietary ginger decreased blood glucose
      and MDA level, increased reproductive organ weights and testosterone level,
      improved semen quantity and motility, and ameliorated the SOD, CAT and GPx
      activities as well as testis AST, ALT, LDH and ALP activities. Intake of ginger
      roots improves the antioxidant and androgenic reproductive function of male
      diabetic rats in addition to its antidiabetic property.

PMID- 23862760
TI  - An off-on COX-2-specific fluorescent probe: targeting the Golgi apparatus of
      cancer cells.
AB  - Identifying cancer cells and quantifying cancer-related events in particular
      organelles in a rapid and sensitive fashion are important for early diagnosis and
      for studies on pathology and therapeutics of cancers. Herein a smart "off-on"
      cyclooxygenase-2-specific fluorescence probe (ANQ-IMC-6), able to report the
      presence of cancer cells and to image Golgi-related events, has been designed and
      evaluated. Cyclooxygenase-2 (COX-2) has been used as imaging target in the probe
      design, since this enzyme is a biomarker of virtually all cancer cell lines. In
      the free state in aqueous solution, ANQ-IMC-6 mainly exists in a folded
      conformation where probe fluorescence is quenched through photoinduced electron
      transfer between the fluorophore acenaphtho[1,2-b]quinoxaline (ANQ) and the
      recognition group, indomethacin (IMC). Fluorescence is turned on, by restraining
      the photoinduced electron transfer, when ANQ-IMC-6 is forced to adopt the
      unfolded state following binding to COX-2 in the Golgi apparatus of cancer cells.
      ANQ-IMC-6 provides high signal-to-background staining and has been successfully
      used to rapidly differentiate cancer cells from normal cells when using flow
      cytometry and one- and two-photon fluorescence microscopic imaging. Furthermore,
      ANQ-IMC-6 may be able to visualize dynamic changes of the Golgi apparatus during
      cancer cell apoptosis, with possible application to early diagnosis. 

PMID- 23862761
TI  - Uterotrophic and Hershberger assays for endocrine disruption properties of
      plastic food contact materials polypropylene (PP) and polyethylene terephthalate
      (PET).
AB  - Plasticizers or plastic materials such as phthalates, bisphenol-A (BPA), and
      styrene are widely used in the plastic industry and are suspected endocrine
      disrupting chemicals (EDC). Although plastic materials such as polypropylene (PP)
      and polyethylene terephthalate (PET) are not EDC and are considered to be safe,
      their potential properties as EDC have not been fully investigated. In this
      study, plastic samples eluted from plastic food containers (PP or PET) were
      investigated in Sprague-Dawley rats using Hershberger and uterotrophic assays. In
      the Hershberger assay, 6-wk-old castrated male rats were orally treated for 10
      consecutive days with plastic effluent at 3 different doses (5 ml/kg) or vehicle
      control (corn oil, 1 ml/100 g) to determine the presence of both anti-androgenic
      and androgenic effects. Testosterone (0.4 mg/ml/kg) was subcutaneously
      administered for androgenic evaluation as a positive control, whereas
      testosterone (0.4 mg/ml/kg) and flutamide (3 mg/kg/day) were administered to a
      positive control group for anti-androgenic evaluation. The presence of any anti
      androgenic or androgenic activities of plastic effluent was not detected. Sex
      accessory tissues such as ventral prostate or seminal vesicle showed no
      significant differences in weight between treated and control groups. For the
      uterotrophic assay, immature female rats were treated with plastic effluent at
      three different doses (5 ml/kg), with vehicle control (corn oil, 1 ml/100 g), or
      with ethinyl estradiol (3 MUg/kg/d) for 3 d. There were no significant
      differences between test and control groups in vagina or uterine weight. Data
      suggest that effluents from plastic food containers do not appear to produce
      significant adverse effects according to Hershberger and uterotrophic assays. 

PMID- 23862762
TI  - Levels of lead, arsenic, mercury and cadmium in clays for oral use on the Dutch
      market and estimation of associated risks.
AB  - Pregnant women in Africa, Asia and Suriname, and some immigrants in Western
      societies, traditionally consume clay products known by a variety of names such
      as mabele, calabash chalk, sikor and pimba. Furthermore, clay is used for health
      purposes in Western societies. Because certain clays can contain high levels of
      metals and metalloids, the aim of this study was to determine lead, arsenic,
      mercury and cadmium in clay products for oral use available on the Dutch market.
      Traditional clays originating from Africa (n = 10) and Suriname (n = 26), and
      health clays (n = 27) were sampled from 2004 up to and including 2012. Total
      metal and metalloid contents were measured by ICP-MS and showed maximum levels of
      lead, arsenic, mercury and cadmium of 99.7, 45.1, 2.2 and 0.75 mg kg-1,
      respectively. In the absence of maximum limits for these type of clays, the
      potential exposure was estimated from the determined concentration, the estimated
      daily use level of the clays, and the estimated bioaccessibility of the different
      metals and arsenic. The intake estimates were compared with existing health-based
      guidance values. For lead, the use of 34 of the 36 traditional clays and two of
      the 27 health clays would result in intake levels exceeding the toxicological
      limit by up to 20-fold. Use of 15 of the 35 traditional clays and 11 of the 27
      health clays would result in intake levels exceeding the toxicological limit for
      inorganic arsenic by up to 19-fold. Although limited bioaccessibility from the
      clay may limit the exposure and exceedance of the health-based guidance values,
      it was concluded that lead and arsenic intakes from some clay products could be
      of concern also because of their use by pregnant women and the potential
      developmental toxicity. As a result the use of these products, especially by
      pregnant women, should be discouraged.

PMID- 23862764
TI  - Variability in oxidative stress biomarkers following a maximal exercise test.
AB  - The oxidative stress response to maximal exercise may provide useful clinical
      biomarkers for assessing redox homeostasis. The aim was to determine the between
      individual variability in the exercise-induced change in oxidative stress
      measures and investigate predictors of these responses. Plasma F2-isoprostanes
      (Isop), protein carbonyls (PCs), glutathione peroxidase (GPX) activity and total
      antioxidant capacity (TAC) were measured before and after a maximal treadmill
      exercise test. Exercise produced significant increases in Isop (27.0%), PC (6.2%)
      and GPX (7.8%). There were large between-individual coefficients of variation:
      Isop (152%), PC, (240%), GPX (130%) and TAC (243%).

PMID- 23862763
TI  - Serum methylation levels of TAC1. SEPT9 and EYA4 as diagnostic markers for early
      colorectal cancers: a pilot study.
AB  - OBJECTIVE: To identify methylated genes in serum with diagnostic potentials for
      early colorectal cancer (CRC). METHODS: Serum methylation levels of up to 12
      genes were measured in two sets of serum samples with the second set from 26
      stage I CRC patients and 26 age/gender-matched controls. RESULTS: Serum
      methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants
      between stage I CRC and healthy controls. Combination of TAC1 and SEPT9 rendered
      73.1% sensitivity with 92.3% specificity. CONCLUSION: Serum methylation levels of
      TAC1. SEPT9 and EYA4 may be useful biomarkers for early detection of CRC though a
      validation study is necessary.

PMID- 23862766
TI  - Observation of individual semiconducting nanoparticle collisions by stochastic
      photoelectrochemical currents.
AB  - We describe a method to detect individual semiconducting nanoparticles (NPs)
      using the photoelectrochemical (PEC) current measured at an ultramicroelectrode
      (UME). We use photooxidation of MeOH by TiO2 NPs as a model system of
      photocatalysis in solution. NPs suspended in MeOH under constant illumination
      produce valence-band holes that oxidize MeOH. The electrons are collected at the
      UME, and the current-versus-time data show discrete current changes that are
      assigned to particle-by-particle interactions of the NPs with the UME. The
      stepwise changes in the photocurrent denote irreversible attachment of NPs to Pt
      UMEs (<30 MUm diameter). We found that accumulation of electrons in the
      conduction band by the NPs is not enough to explain the stochastic PEC currents.
      We propose that the observed anodic steps have a PEC nature and are due to
      photooxidation of MeOH by the NPs at the electrode surface. 

PMID- 23862765
TI  - Diagnostic significance of DOG-1 and PKC-theta expression and c-Kit/PDGFRA
      mutations in gastrointestinal stromal tumours.
AB  - OBJECTIVE: To investigate discovered on gastrointestinal stromal tumor (GIST)-1
      (DOG-1) and protein kinase C-theta (PKC-theta) expression in a series of GISTs
      and determine the sensitivity, specificity, and diagnostic value of these two
      antigens. METHODS: Immnunohistochemistry (IHC) was used to detect CD117, DOG-1,
      PKC-theta, CD34, Ki-67, alpha-smooth muscle actin (SMA), S100, and Desmin
      expression in 147 GISTs and 51 non-GISTs. c-Kit gene (exons 9, 11, 13, and 17)
      and platelet-derived growth factor receptor-alpha (PDGFRA) gene (exons 12 and 18)
      mutations were also detected. RESULTS: About 94.5% GISTs were CD117 positive, 96%
      were DOG-1 positive, and 90.5% were PKC-theta positive. DOG-1 had a specificity
      of 100%, while CD117 and PKC-theta had a specificity of 90% and 80%,
      respectively. There was no significant difference between DOG-1 and PKC-theta
      expressions when compared to CD117 expression. In 30 out of 42 (71.5%) GISTs, a c
      Kit gene mutation was found, and in 3 out of 42 cases (7%), PDGFRA was mutated.
      Wild-type c-Kit/PDGFRA genes accounted for 21.5% (9/42). Most c-Kit gene
      mutations were found to be located at exon 11, mainly as in-frame deletions.
      Mutations in exon 9 were all missense mutations. Most PDGFRA gene mutations were
      found in exon 18, codon 842. c-Kit gene mutations in exons 13 and 17, and the
      PDGFRA gene mutation in exon 12 were not detected. CONCLUSIONS: Compared to
      CD117, DOG-1 is a biomarker with higher sensitivity and specificity. The
      combination of CD117 and DOG-1 can be used to improve the diagnosis of GIST.
      Although PKC-theta has a lower specificity than DOG-1, it can be a useful
      biomarker, especially in CD117(-) and/or DOG-1(-) cases.

PMID- 23862767
TI  - Turning hardwood dissolving pulp polysaccharide residual material into barrier
      packaging.
AB  - Birch chips were subjected to pilot-scale pre-hydrolysis under various sets of
      conditions to mimic a pre-hydrolysis step in a dissolving pulp process. The
      process generates residual process liquor, a wood hydrolysate, and the treated
      chips may be directly utilized in a dissolving process. The wood hydrolysates
      were rich in xylan and utilized in the production of fully renewable films that
      provide very good oxygen barrier function and mechanical integrity also at high
      relative humidity. Membrane filtration had an effect in enriching higher
      molecular weight fractions from the hydrolysates, but noteworthy, a hydrolysate
      used in the crude state without any membrane filtration performed just as well as
      upgraded fractions in forming films providing acceptable tensile properties and a
      good barrier against oxygen permeation.

PMID- 23862768
TI  - Cold adaptation of fungi obtained from soil and lake sediment in the Skarvsnes
      ice-free area, Antarctica.
AB  - A total of 71 isolates were collected from lake sediment and soil surrounding
      lakes in the Skarvsnes area, Antarctica. Based on ITS region sequence similarity,
      these isolates were classified to 10 genera. Twenty-three isolates were
      categorized as ascomycetous fungi from five genera (Embellisia, Phoma, Geomyces,
      Tetracladium or Thelebolus) and 48 isolates were categorized as basidiomycetous
      fungi in five genera (Mrakia, Cryptococcus, Dioszegia, Rhodotorula or
      Leucosporidium). Thirty-five percent of culturable fungi were of the genus
      Mrakia. Eighteen isolates from eight genera were selected and tested for both
      antifreeze activity and capacity for growth under temperatures ranging from -1 to
      25  degrees C. Rhodotorula sp. NHT-2 possessed a high degree of sequence homology
      with R. gracialis, while Leucosporidium sp. BSS-1 possessed a high degree of
      sequence homology with Leu. antarcticum (Glaciozyma antarctica), and these two
      isolates demonstrated antifreeze activity. All isolates examined were capable of
      growth at -1  degrees C. Mrakia spp., while capable of growth at -1  degrees C,
      did not demonstrate any antifreeze activity and exhibited only limited secretion
      of extracellular polysaccharides. Species of the genus Mrakia possessed high
      amounts of unsaturated fatty acids, suggesting that members of this genus have
      adapted to cold environments by increasing their membrane fluidity. 

PMID- 23862769
TI  - Investigating word associations in a schizotypy sample: contrasting implicit and
      explicit processing.
AB  - INTRODUCTION: Schizotypy is a useful schizophrenia analogue that controls for
      confounding factors such as medication and general intellectual decline. In the
      current study this analogue approach was used to examine implicit/explicit and
      direct/indirect semantic memory function. This is the first study to examine both
      implicit and explicit semantic access in the same schizotypy sample. METHODS:
      Participants completed four semantic tasks: (1) implicit indirect priming, (2)
      implicit direct priming, (3) explicit object (indirect) task, and (4) explicit
      association (direct) task. The schizophrenia literature suggests that semantic
      impairments are associated with thought disorder. As such, participants were
      divided into low (n=18) and high (n=18) schizotypy groups based on their
      responses to a thought disorder subscale of the Oxford Liverpool Inventory of
      Feelings and Experiences (O-Life) scale. RESULTS: In terms of implicit
      performance, the high schizotypy group demonstrated increased direct priming but
      nonsignificant indirect priming. The low schizotypy group demonstrated no
      significant difference in direct and indirect priming. Performance on the
      explicit tasks was equivalent between the two groups for direct stimuli. On the
      indirect explicit task, high schizotypy was associated with an increase in
      errors. CONCLUSIONS: Increased direct priming in high schizotypy is equivalent to
      that seen in schizophrenia, which has been interpreted as increased spreading of
      activation. Abnormal performance using the indirect stimuli was found across
      implicit and explicit versions. The relevance of these findings to schizophrenia
      are discussed.

PMID- 23862770
TI  - 'He lacks his fatherhood': safer conception technologies and the biological
      imperative for fatherhood among recently-diagnosed Xhosa-speaking men living with
      HIV in South Africa.
AB  - This paper explores notions of fatherhood and their linkages to fertility desires
      and intentions among a treatment-naive cohort of Xhosa-speaking male key
      informants living with HIV, aged 20-53 in Cape Town, South Africa. Analysis is
      based on an initial 27, and 20 follow-up, interviews with men who were part of a
      study that assessed the acceptability of safer conception and alternative
      parenting strategies among men and women newly diagnosed with HIV to inform an
      intervention. Grounded theory analysis revealed themes related to the cultural
      imperative of biologically-connected fatherhood. Certain safer-conception
      strategies aimed at minimising the risk of HIV transmission were perceived as
      threats to paternity. These findings suggest that understanding of social and
      cultural beliefs related to notions of paternity and fatherhood may inform the
      implementation of acceptable safer-conception options for HIV-positive men and
      their infected and uninfected female partners in a high-HIV prevalence, low
      resource setting. 

PMID- 23862771
TI  - Toxic rather than neuropharmacological effect of Ternstroemia sylvatica fruits
      and identification of 28-O-[beta-l-6-rhamnopyranosyl]-R1-barrigenol as a new
      compound with toxic effects in mice.
AB  - CONTEXT: Fruits of Ternstroemia sylvatica Schltdl. and Cham. (Theaceae) are used
      in Mexican traditional medicine to alleviate anxiety, sleep disorders and
      seizures; however, the active principles have not been identified. OBJECTIVE: To
      identify the neuroactive principles of T. sylvatica fruits using
      neuropharmacological tests on mice. MATERIALS AND METHODS: The methanol and
      aqueous extracts of pericarp or seeds of T. sylvatica fruits were
      intraperitoneally administered (1-562 mg/kg, single doses) to mice. The
      exploratory cylinder, hole board, open field, Rota-rod and sodium pentobarbital
      induced hypnosis tests were used to evaluate the CNS depressant effect after 30
      min single administration of extracts. From aqueous seeds extract, triterpene
      glycoside 28-O-[beta-l-6-rhamnopyranosyl]-R1-barrigenol was isolated an active
      compound. RESULTS: Crude extracts of T. sylvatica fruits, separated from seed and
      pericarp, showed sedative effect in mice. The aqueous (ED50 = 4.9 +/- 0.8 mg/kg)
      seed extracts is the most active among them. This extract also decrease locomotor
      activity and disrupt motor coordination of mice. This extract was also the most
      toxic extract (LD50 = 5.0 +/- 1.4 mg/kg; i.p.). The triterpene glycoside 28-O
      [beta-l-6-rhamnopyranosyl]-R1-barrigenol was identified in this extract as one of
      the active sedative compounds (ED50 = 0.12 +/- 0.01 mg/kg) also with toxic effect
      (LD50 = 1.11 +/- 0.23 mg/kg). CONCLUSION: The results suggest that T. sylvatica
      fruits has toxic activity rather than CNS depressant activity in mice and that
      this effect might be related to the presence of 28-O-[beta-l-6-rhamnopyranosyl]
      R1-barrigenol, one of the active principles of T. sylvatica fruits with sedative
      and toxic effect.

PMID- 23862773
TI  - Safety and efficacy of romiplostim in patients with eltrombopag-resistant or 
      intolerant immune thrombocytopenia.

PMID- 23862774
TI  - New patents of fixed combinations of nasal antihistamines and corticosteroids in
      allergic rhinitis.
AB  - During the last few years, fixed combinations of intranasal antihistamines and
      corticosteroids have been introduced for treatment of allergic rhinitis. The aim
      of this systematic review was to assess recent patents and clinical evidence for
      fixed combinations of intranasal antihistamines and intranasal corticosteroids in
      allergic rhinitis. Data base searches revealed that intranasal combinations of
      the antihistamine azelastine with the corticosteroids mometasone furoate,
      ciclesonide and fluticasone propionate, respectively, have been patented. Four
      randomized, double-blinded, parallel-group, placebo-controlled, multicenter
      trials sponsored by the manufacturer evaluated the fixed combination of
      intranasal azelastine 125 ug and fluticasone propionate 50 ug administered as one
      dose per nostril b.i.d. in patients with moderate-to-severe symptomatic allergic
      rhinitis >= 12 years of age. Three of the studies were published as a meta
      analysis which found the fixed combination of azelastine and fluticasone
      propionate statistically significantly more efficacious in reducing baseline
      total nasal symptom score by 5.7 as compared to azelastine (4.4; P < 0.001),
      fluticasone propionate (5.1; P < 0.001) and placebo (3.0; P < 0.001). The
      findings were supported by secondary assessments of scores of specific nasal and
      ocular symptoms. Pharmacokinetic studies have revealed no drug-drug interactions
      but a discrete increase in bioavailability of fluticasone propionate which was
      considered clinically unimportant. Further efficacy and quality-of-life studies
      of combination products of nasal antihistamines and corticosteroids are needed,
      especially, in primary care settings and in children before fixed combination
      treatment can be considered first line therapy in allergic rhinitis. Fixed
      combination treatment of azelastine and fluticasone propionate may offer
      additional benefit to selected populations of adolescents and adults with
      moderate-to-severe symptoms.

PMID- 23862775
TI  - Optically optimized photoluminescent and interferometric biosensors based on
      nanoporous anodic alumina: a comparison.
AB  - Herein, we present a comparative study about the sensing performance of optical
      biosensors based on photoluminescence spectroscopy (PLS) and reflectometric
      interference spectroscopy (RIfS) combined with nanoporous anodic alumina (NAA)
      platforms when detecting different analytes under distinct adsorption conditions.
      First, NAA platforms are structurally engineered in order for optimizing the
      optical signals obtained by PLS and RIfS. Then, the most optimal NAA platforms
      combined with PLS and RIfS are quantitatively compared by detecting two different
      analytes: d-glucose and l-cysteine under nonspecific and specific adsorption
      conditions, respectively. The obtained results demonstrate that such parameters
      as the analyte nature and adsorption conditions play a direct role in the sensing
      performance of these platforms. However, as this study demonstrates, PLS-NAA
      platforms are more sensitive than RIfS-NAA ones. The former shows better
      linearity (i.e., proportional change in the sensing parameter with analyte
      concentration), higher sensitivity toward analytes (i.e., sharper change in the
      sensing parameter with analyte concentration), and lower limit of detection
      (i.e., minimum detectable concentration of analyte). 

PMID- 23862777
TI  - Effectiveness of focused source generation methods with consideration of
      interaural time and level difference.
AB  - Several methods have been proposed for the generation of the focused source,
      usually a virtual monopole source positioned in between the loudspeaker array and
      the listener. The problem of pre-echoes of the common analytical methods has been
      noticed, and the most concise method to cope with this problem is the angular
      weight method. In this paper, the interaural time and level difference, which are
      well related to the localization cues of human auditory systems, will be used to
      further investigate the effectiveness of the focused source generation methods.
      It is demonstrated that the combination of angular weight method and the
      numerical pressure matching method has comparatively better performance in a
      given reconstructed area. 

PMID- 23862772
TI  - Diabetes: glycaemic control in type 2 (drug treatments).
AB  - INTRODUCTION: Diabetes mellitus is a progressive disorder of glucose metabolism.
      It is estimated that about 285 million people between the ages of 20 and 79 years
      had diabetes worldwide in 2010, or 5% of the adult population. Type 2 diabetes
      may occur with obesity, hypertension, and dyslipidaemia (the metabolic syndrome),
      which are powerful predictors of cardiovascular disease. Without adequate blood
      glucose-lowering treatment, blood glucose levels may rise progressively over time
      in people with type 2 diabetes. Microvascular and macrovascular complications may
      develop. METHODS AND OUTCOMES: We conducted a systematic review and aimed to
      answer the following clinical question: What are the effects of blood-glucose
      lowering medications in adults with type 2 diabetes? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to February 2010
      (Clinical Evidence reviews are updated periodically, please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      194 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review we present information
      relating to the effectiveness and safety of the following interventions: alpha
      glucosidase inhibitors (AGIs), combination treatment (single, double, and
      triple), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP
      1) analogues, insulins (including conventional [human] and analogue, different
      regimens, different length of action), meglitinides, metformin, sulphonylureas,
      and thiazolidinediones.

PMID- 23862778
TI  - Comment on "Short-term acoustic forecasting via artificial neural networks for
      neonatal intensive care units" [J. Acoust. Soc. Am. 132, 3234-3239 (2012)].
AB  - In contrast to common expectations, the noise levels measured in hospital wards
      are known to be high with little day-night variation, potentially having negative
      effects on the patient outcomes and the work performance of the staff members,
      and considerable research attention has been drawn to such adverse acoustic
      conditions in healthcare environments. Recently, Young et al. [J. Acoust. Soc.
      Am. 132(5), 3234-3239 (2012)] proposed to use an artificial neural network (ANN)
      to predict the hourly energy-equivalent sound pressure level (Leq, 1h),
      particularly targeting neonatal intensive care units. Despite the timeliness of
      the study and the potential benefits of an "acoustic forecasting" model, the
      proposed scheme appears to be underdeveloped in a few important aspects, which
      this letter attempts to address. In particular, the prediction of a simpler time
      series smoothing technique was equally or more accurate compared to that of the
      ANN. In addition, the percentage error used to indicate the prediction accuracy
      was not only perceptually irrelevant but also misleading given the narrow
      distribution of test data. Furthermore, this letter raises the more general
      question whether the sound pressure level may meaningfully be modeled solely
      based on the past time-series. 

PMID- 23862779
TI  - Comments on "A theoretical model of the pressure field arising from asymmetric
      intraglottal flows applied to a two-mass model of the vocal folds" [J. Acoust.
      Soc. Am. 130, 389-403 (2011)].
AB  - After demonstrating by means of an in vitro model experiment that the flow in the
      glottis can become asymmetric, Erath et al. [J. Acoust. Soc. Am. 130, 389-403
      (2011)] propose a theory to estimate the resulting asymmetry in the lateral
      hydrodynamic force on the vocal folds. A wall-jet attached to one side of the
      divergent downstream part of the glottis is considered. The model assumes that
      the wall is a flat plate and that the jet separates at the glottal exit. They
      implement this so-called Boundary Layer Estimation of Asymmetric Pressure force
      model in a lumped two mass model of the vocal folds. This should allow them to
      study the impact of the asymmetry on voiced sound production. A critical
      discussion of the merits and shortcomings of the model is provided. It predicts
      discontinuities in the time dependency of the lateral force. It predicts this
      force to be independent from the glottal opening, which is not reasonable. An
      alternative model is proposed, which avoids these problems and predicts that
      there is a minimum glottal opening below which the wall-jet does not separate
      from the wall at the glottal exit. This is in agreement with the experimental
      results provided by Erath et al. 

PMID- 23862780
TI  - Comparative temporary threshold shifts in a harbor porpoise and harbor seal, and
      severe shift in a seal.
AB  - Anthropogenic noise may cause temporary hearing threshold shifts (TTSs) in marine
      mammals. Tests with identical methods show that harbor porpoises are more
      susceptible to TTS induced by octave-band white noise (OBN) centered around 4 kHz
      than harbor seals, although their unmasked (basic) hearing thresholds for that
      frequency are similar. A harbor seal was exposed for 1 h to an OBN with a very
      high sound pressure level (SPL), 22-30 dB above levels causing TTS onset. This
      elicited 44 dB TTS; hearing recovered within 4 days. Thus, for this signal and
      this single exposure, permanent threshold shift requires levels at least 22 dB
      above TTS onset levels. The severe TTS in the seal suggests that the critical
      level (above which TTS increases rapidly with increasing SPL) is between 150 and
      160 dB re 1 MUPa for a 60 min exposure to OBN centered at 4 kHz. In guidelines on
      TTS in marine mammals produced by policy makers in many countries, TTS is assumed
      to follow the equal energy hypothesis, so that when the sound exposure levels of
      fatiguing sounds are equal, the same TTS is predicted to be induced. However,
      like previous studies, the present study calls this model into question. 

PMID- 23862781
TI  - Flight parameter estimation using time delay and intersensor multipath delay
      measurements from a small aperture acoustic array.
AB  - A ground-based acoustic sensor array can be used to estimate the complete set of
      flight parameters of a jet aircraft or other airborne source of broadband sound
      in transit by measuring the differential time of arrival (DTOA), or the time
      delay, of the direct path signal at each sensor pair of the array over a
      sufficiently long period of time. This paper studies the possibility of using
      intersensor multipath delay measurements to improve the precision of the flight
      parameter estimates for a small aperture array, without increasing the array's
      intersensor spacing or the observation time for more time delay measurements.
      Intersensor multipath delay is defined as the DTOA of the direct path signal at
      one sensor and the ground-reflected path signal at another sensor. The flight
      parameter estimation algorithm is formulated and a simplified Cramer-Rao lower
      bound error analysis is presented, which shows that the standard deviations in
      the flight parameter estimates are greatly reduced when intersensor multipath
      delay measurements are used together with time delay measurements. The
      effectiveness of the proposed flight parameter estimation method for small
      aperture arrays is verified using both simulated and real data. 

PMID- 23862782
TI  - Empirical and quadrature approximation of acoustic field and array response
      probability density functions.
AB  - Numerical methods are presented for approximating the probability density
      functions (pdf's) of acoustic fields and receiver-array responses induced by a
      given joint pdf of a set of acoustic environmental parameters. An approximation
      to the characteristic function of the random acoustic field (the inverse Fourier
      transform of the field pdf) is first obtained either by construction of the
      empirical characteristic function (ECF) from a random sample of the acoustic
      parameters, or by application of generalized Gaussian quadrature to approximate
      the integral defining the characteristic function. The Fourier transform is then
      applied to obtain an approximation of the pdf by a continuous function of the
      field variables. Application of both the ECF and generalized Gaussian quadrature
      is demonstrated in an example of a shallow-water ocean waveguide with two
      dimensional uncertainty of sound speed and attenuation coefficient in the ocean
      bottom. Both approximations lead to a smoother estimate of the field pdf than
      that provided by a histogram, with generalized Gaussian quadrature providing a
      smoother estimate at the tails of the pdf. Potential applications to acoustic
      system performance quantification and to nonparametric acoustic signal processing
      are discussed. 

PMID- 23862783
TI  - Broadband acoustic quantification of stratified turbulence.
AB  - High-frequency broadband acoustic scattering techniques have enabled the remote,
      high-resolution imaging and quantification of highly salt-stratified turbulence
      in an estuary. Turbulent salinity spectra in the stratified shear layer have been
      measured acoustically and by in situ turbulence sensors. The acoustic frequencies
      used span 120-600 kHz, which, for the highly stratified and dynamic estuarine
      environment, correspond to wavenumbers in the viscous-convective subrange (500
      2500 m(-1)). The acoustically measured spectral levels are in close agreement
      with spectral levels measured with closely co-located micro-conductivity probes.
      The acoustically measured spectral shapes allow discrimination between scattering
      dominated by turbulent salinity microstructure and suspended sediments or swim
      bladdered fish, the two primary sources of scattering observed in the estuary in
      addition to turbulent salinity microstructure. The direct comparison of salinity
      spectra inferred acoustically and by the in situ turbulence sensors provides a
      test of both the acoustic scattering model and the quantitative skill of
      acoustical remote sensing of turbulence dissipation in a strongly sheared and
      salt-stratified estuary. 

PMID- 23862784
TI  - Integrating the energy flux method for reverberation with physics-based seabed
      scattering models: modeling and inversion.
AB  - During the past 30 years, one of the major accomplishments in ocean acoustics is
      the improvement of understanding seabed scattering, resulting from a significant
      effort of both at-sea measurement and theoretical modeling. [Jackson and
      Richardson: High-Frequency Seafloor Acoustics, 2007]. Benefiting from this
      accomplishment, this paper integrates the energy flux method for shallow-water
      (SW) reverberation [Zhou, (Chinese) Acta Acust. 5, 86-99 (1980)] with the physics
      based seabed scattering models. This integration directly and intuitively results
      in general expressions for SW reverberation in the angular and modal domains. The
      latter expression is the same as the modal reverberation expression derived from
      the Green's function and boundary perturbation method by Tracey and Schmidt [IEEE
      J. Ocean. Eng. 22, 317-331(1997)]. The integration also results in a simple
      relationship between the classic boundary scattering cross sections and the modal
      scattering matrix in SW waveguides. The bottom roughness spectrum and sediment
      volume scattering cross section at low grazing angles are inverted in a frequency
      range of 150-2500 Hz from the wideband long-range reverberation data by using the
      Biot seabed geoacoustic model. The results may offer some reference data sets for
      future analysis of the low-frequency seabed scattering mechanisms. 

PMID- 23862785
TI  - Inversion for a moving spherical target's positional, structural, and speed
      parameters.
AB  - The broadband scattering characteristics of a target may be used to distinguish
      its echoes from those of clutter. In a shallow water situation, the echo from the
      target will consist of a sequence of pulses corresponding to the various coherent
      combinations of incident and backscattered multipath arrivals. Thus, the
      interference effects of the waveguide propagation can have a significant effect
      upon the received echo and thus also affect the classification of the target from
      the echo. In addition, the target may be moving, in which case the received echo
      is also Doppler-shifted. The purpose of this paper is to investigate the
      simultaneous determination of a spherical target's position (range and depth)
      within a waveguide, its radial speed, its radius, its shell thickness, and the
      elastic parameters of the shell. It will be shown that many of these parameters
      can be accurately estimated from a single wideband echo, even in the presence of
      significant noise. The marginal probability distributions of the parameter values
      will also be investigated. It will be seen that the positional and speed
      parameters of the sphere can be determined to high precision. The other
      parameters are determined with varying degrees of precision. 

PMID- 23862786
TI  - Under-ice ambient noise in Eastern Beaufort Sea, Canadian Arctic, and its
      relation to environmental forcing.
AB  - This paper analyzes an 8-month time series (November 2005 to June 2006) of
      underwater noise recorded at the mouth of the Amundsen Gulf in the marginal ice
      zone of the western Canadian Arctic when the area was >90% ice covered. The time
      series of the ambient noise component was computed using an algorithm that
      filtered out transient acoustic events from 7-min hourly recordings of total
      ocean noise over a [0-4.1] kHz frequency band. Under-ice ambient noise did not
      respond to thermal changes, but showed consistent correlations with large-scale
      regional ice drift, wind speed, and measured currents in upper water column. The
      correlation of ambient noise with ice drift peaked for locations at ranges of
      ~300 km off the mouth of the Amundsen Gulf. These locations are within the multi
      year ice plume that extends westerly along the coast in the Eastern Beaufort Sea
      due to the large Beaufort Gyre circulation. These results reveal that ambient
      noise in Eastern Beaufort Sea in winter is mainly controlled by the same
      meteorological and oceanographic forcing processes that drive the ice drift and
      the large-scale circulation in this part of the Arctic Ocean.

PMID- 23862787
TI  - Time-angle sensitivity kernels for sound-speed perturbations in a shallow ocean.
AB  - Acoustic waves traveling in a shallow-water waveguide produce a set of multiple
      paths that can be characterized as a geometric approximation by their travel time
      (TT), direction of arrival (DOA), and direction of departure (DOD). This study
      introduces the use of the DOA and DOD as additional observables that can be
      combined to the classical TT to track sound-speed perturbations in an oceanic
      waveguide. To model the TT, DOA, and DOD variations induced by sound-speed
      perturbations, the three following steps are used: (1) In the first-order Born
      approximation, the Frechet kernel provides a linear link between the signal
      fluctuations and the sound-speed perturbations; (2) a double-beamforming
      algorithm is used to transform the signal fluctuations received on two source
      receiver arrays in the time, receiver-depth, and source-depth domain into the
      eigenray equivalent measured in the time, reception-angle and launch angle
      domain; and finally (3) the TT, DOA, and DOD variations are extracted from the
      double-beamformed signal variations through a first-order Taylor development. As
      a result, time-angle sensitivity kernels are defined and used to build a linear
      relationship between the observable variations and the sound-speed perturbations.
      This approach is validated with parabolic-equation simulations in a shallow-water
      ocean context. 

PMID- 23862788
TI  - Identification and target strength of orange roughy (Hoplostethus atlanticus)
      measured in situ.
AB  - It is often assumed that in situ target strength (TS) measurements from dispersed
      fish are representative of the surveyed schooling fish. For in situ TS
      measurements of orange roughy in deep water, it has been difficult to validate
      the target species, individual lengths, and tilt angles and how representative
      these are of schooling fish. These problems have been addressed by attaching an
      acoustic optical system (AOS) to a trawl net. The AOS enables in situ
      measurements of TS and volume backscattering strength (Sv) at 38 and 120 kHz with
      optical verification of species and stereo camera measurements of fish length and
      tilt angle. TS estimates believed representative of the schooling population were
      derived by (1) weighting the frequency-dependent TS values by the Sv frequency
      difference distribution of orange roughy schools and (2) weighting the in situ TS
      measurements with an assumed tilt angle distribution. The 120-kHz TS estimates
      were less sensitive to variations in frequency difference and tilt angle,
      suggesting that this frequency may be better for biomass estimates than 38 kHz,
      the traditional survey frequency. Computations performed with an anatomically
      detailed scattering model agree with measurements of TS at both frequencies over
      a range of tilt angles.

PMID- 23862789
TI  - Elliptical acoustic particle motion in underwater waveguides.
AB  - Elliptical particle motion, often encountered in acoustic fields containing
      interference between a source signal and its reflections, can be quantified by
      the degree of circularity, a vector quantity formulated from acoustic particle
      velocity, or vector intensity measurements. Acoustic analysis based on the degree
      of circularity is expected to find application in ocean waveguides as its spatial
      dependence relates to the acquisition geometry, water column sound speed, surface
      conditions, and bottom properties. Vector sensor measurements from a laboratory
      experiment are presented to demonstrate the depth dependence of both the degree
      of circularity and an approximate formulation based on vertical intensity
      measurements. The approximation is applied to vertical intensity field
      measurements made in a 2006 experiment off the New Jersey coast (in waters 80 m
      deep) to demonstrate the effect of sediment structure on the range dependence of
      the degree of circularity. The mathematical formulation presented here
      establishes the framework to readily compute the degree of circularity from
      experimental measurements; the experimental examples are provided as evidence of
      the spatial and frequency dependence of this fundamental vector property.

PMID- 23862790
TI  - Introduction to the special issue on sediment acoustics.

PMID- 23862791
TI  - Bayesian geoacoustic inversion of single hydrophone light bulb data using warping
      dispersion analysis.
AB  - This paper presents geoacoustic inversion of a light bulb implosion recorded
      during the Shallow Water 2006 experiment. The source is low frequency and
      impulsive, the environment is shallow water, and the acoustic signal is recorded
      using a single receiver. In this context, propagation is described by modal
      theory, and inversion is carried out by matching modal dispersion curves in the
      time-frequency domain. Experimental dispersion curves are estimated using an
      advanced signal processing method called warping, allowing inversion to be
      carried out at a relatively short range (~/=7 km). Moreover, the inversion itself
      is performed using Bayesian methodology. This allows inference of the seabed
      structure from the data, including the number of seabed layers resolved, optimal
      estimates of the seabed parameters, and quantitative uncertainty estimates.
      Inversion results of the experimental data are in good agreement with both ground
      truth and estimates from other experimental data in the same region.

PMID- 23862792
TI  - Mid frequency shallow water fine-grained sediment attenuation measurements.
AB  - Attenuation is perhaps the most difficult sediment acoustic property to measure,
      but arguably one of the most important for predicting passive and active sonar
      performance. Measurement techniques can be separated into "direct" measurements
      (e.g., via sediment probes, sediment cores, and laboratory studies on "ideal"
      sediments) which are typically at high frequencies, O(10(4)-10(5)) Hz, and
      "indirect" measurements where attenuation is inferred from long-range propagation
      or reflection data, generally O(10(2)-10(3)) Hz. A frequency gap in measurements
      exists in the 600-4000 Hz band and also a general acknowledgement that much of
      the historical measurements on fine-grained sediments have been biased due to a
      non-negligible silt and sand component. A shallow water measurement technique
      using long range reverberation is critically explored. An approximate solution
      derived using energy flux theory shows that the reverberation is very sensitive
      to depth-integrated attenuation in a fine-grained sediment layer and separable
      from most other unknown geoacoustic parameters. Simulation using Bayesian methods
      confirms the theory. Reverberation measurements across a 10 m fine-grained
      sediment layer yield an attenuation of 0.009 dB/m/kHz with 95% confidence bounds
      of 0.006-0.013 dB/m/kHz. This is among the lowest values for sediment attenuation
      reported in shallow water.

PMID- 23862793
TI  - Shear wave speed dispersion and attenuation in granular marine sediments.
AB  - The reported compressional wave speed dispersion and attenuation could be
      explained by a modified gap stiffness model incorporated into the Biot model (the
      BIMGS model). In contrast, shear wave speed dispersion and attenuation have not
      been investigated in detail. No measurements of shear wave speed dispersion have
      been reported, and only Brunson's data provide the frequency characteristics of
      shear wave attenuation. In this study, Brunson's attenuation measurements are
      compared to predictions using the Biot-Stoll model and the BIMGS model. It is
      shown that the BIMGS model accurately predicts the frequency dependence of shear
      wave attenuation. Then, the shear wave speed dispersion and attenuation in water
      saturated silica sand are measured in the frequency range of 4-20 kHz. The
      vertical stress applied to the sample is 17.6 kPa. The temperature of the sample
      is set to be 5  degrees C, 20  degrees C, and 35  degrees C in order to change
      the relaxation frequency in the BIMGS model. The measured results are compared
      with those calculated using the Biot-Stoll model and the BIMGS model. It is shown
      that the shear wave speed dispersion and attenuation are predicted accurately by
      using the BIMGS model.

PMID- 23862794
TI  - Range dependent sediment sound speed profile measurements using the image source
      method.
AB  - This paper presents a range dependent sediment sound speed profile measurement
      obtained using the image source method. This technique is based on the analysis
      of the seafloor reflected acoustic wave as a collection of image sources which
      positions are linked with the thick-nesses and the sound speed of the sediment
      stack. The data used were acquired by the NURC in 2009 during the Clutter09
      experiment. The equipment used was an autonomous undersea vehicle towing a 1600
      3500 Hz frequency band source and a 32 m horizontal line array of 32 hydrophones
      at 12 m above the seabed. Under the assumption of locally range independent
      seabed properties, the moving horizontal array provides successive range
      independent sediment sound speed profiles along a track to obtain the range and
      depth dependent structure of the seafloor. Two key steps include recovery of the
      time-varying unknown array shape from the data and spatial filtering of the
      successive sound speed profiles. A comparison of the image source method result
      and seismic data along nearly the same 14 km track indicates that the seabed
      stratigraphy is correctly mapped by this method. 

PMID- 23862795
TI  - Subcritical penetration into rough seafloors due to Bragg scattering.
AB  - A tank experiment and theoretical analysis are carried out to study acoustic
      Bragg scattering by a sinusoidal surface with period 0.3 m and amplitude 2 cm
      between water and sand sediment. The penetrating field is measured in the
      frequency range from 20 to 40 kHz at grazing angles 10 degrees  to 90 degrees  in
      the tank. A theoretical solution for acoustic scattering by the sinusoidal
      surface is derived to explain the interference pattern observed in the
      experiment. The result shows that the minus first order Bragg scattering wave is
      strong enough to interfere with the refracted wave obeying Snell's law, forming
      interference patterns that can be detected experimentally. 

PMID- 23862796
TI  - Estimation of seabed shear-wave velocity profiles using shear-wave source data.
AB  - This paper estimates seabed shear-wave velocity profiles and their uncertainties
      using interface-wave dispersion curves extracted from data generated by a shear
      wave source. The shear-wave source generated a seismic signature over a frequency
      range between 2 and 60 Hz and was polarized in both in-line and cross-line
      orientations. Low-frequency Scholte- and Love-waves were recorded. Dispersion
      curves of the Scholte- and Love-waves for the fundamental mode and higher-order
      modes are extracted by three time-frequency analysis methods. Both the vertically
      and horizontally polarized shear-wave velocity profiles in the sediment are
      estimated by the Scholte- and Love-wave dispersion curves, respectively. A
      Bayesian approach is utilized for the inversion. Differential evolution, a global
      search algorithm is applied to estimate the most-probable shear-velocity models.
      Marginal posterior probability profiles are computed by Metropolis-Hastings
      sampling. The estimated vertically and horizontally polarized shear-wave velocity
      profiles fit well with the core and in situ measurements. 

PMID- 23862798
TI  - Characteristics of sound propagation in shallow water over an elastic seabed with
      a thin cap-rock layer.
AB  - Measurements of low-frequency sound propagation over the areas of the Australian
      continental shelf, where the bottom sediments consist primarily of calcarenite,
      have revealed that acoustic transmission losses are generally much higher than
      those observed over other continental shelves and remain relatively low only in a
      few narrow frequency bands. This paper considers this phenomenon and provides a
      physical interpretation in terms of normal modes in shallow water over a layered
      elastic seabed with a shear wave speed comparable to but lower than the water
      column sound speed. A theoretical analysis and numerical modeling show that, in
      such environments, low attenuation of underwater sound is expected only in narrow
      frequency bands just above the modal critical frequencies which in turn are
      governed primarily by the water depth and compressional wave speed in the seabed.
      In addition, the effect of a thin layer of harder cap-rock overlaying less
      consolidated sediments is considered. Low-frequency transmission loss data
      collected from an offshore seismic survey in Bass Strait on the southern
      Australian continental shelf are analyzed and shown to be in broad agreement with
      the numerical predictions based on the theoretical analysis and modeling using an
      elastic parabolic equation solution for range-dependent bathymetry. 

PMID- 23862797
TI  - Modal investigation of elastic anisotropy in shallow-water environments:
      anisotropy beyond vertical transverse isotropy.
AB  - Theoretical and numerical results are presented for modal characteristics of the
      seismo-acoustic wavefield in anisotropic range-independent media. General
      anisotropy affects the form of the elastic-stiffness tensor, particle-motion
      polarization, the frequency and angular dispersion curves, and introduces near
      degenerate modes. Horizontally polarized particle motion (SH) cannot be ignored
      when anisotropy is present for low-frequency modes having significant bottom
      interaction. The seismo-acoustic wavefield has polarizations in all three
      coordinate directions even in the absence of any scattering or heterogeneity.
      Even weak anisotropy may have a significant impact on seismo-acoustic wave
      propagation. Unlike isotropic and transversely isotropic media with a vertical
      symmetry axis where acoustic signals comprise P-SV modes alone (in the absence of
      any scattering), tilted TI media allow both quasi-P-SV and quasi-SH modes to
      carry seismo-acoustic energy. Discrete modes for an anisotropic medium are best
      described as generalized P-SV-SH modes with polarizations in all three Cartesian
      directions. Conversion to SH is a loss that will mimic acoustic attenuation. An
      in-water explosion will excite quasi-SH. 

PMID- 23862800
TI  - Evaluation of moving-coil loudspeaker and passive radiator parameters using
      normal-incidence sound transmission measurements: theoretical developments.
AB  - The parameters of moving-coil loudspeaker drivers are typically determined using
      direct electrical excitation and measurement. However, as electro-mechano
      acoustical devices, their parameters should also follow from suitable mechanical
      or acoustical evaluations. This paper presents the theory of an acoustical method
      of excitation and measurement using normal-incidence sound transmission through a
      baffled driver as a plane-wave tube partition. Analogous circuits enable key
      parameters to be extracted from measurement results in terms of open and closed
      circuit driver conditions. Associated tools are presented that facilitate
      adjacent field decompositions and derivations of sound transmission coefficients
      (in terms of driver parameters) directly from the circuits. The paper also
      clarifies the impact of nonanechoic receiving tube terminations and the specific
      benefits of downstream field decompositions. 

PMID- 23862799
TI  - Application of nonlinear sliding mode control to ultrasound contrast agent
      microbubbles.
AB  - A sliding mode control system is developed and applied to a spherical model of a
      contrast agent microbubble that simulates its radial response to ultrasound. The
      model uses a compressible form of the Rayleigh-Plesset equation combined with a
      thin-shell model. A nonlinear control law for the second-order model is derived
      and used to design and simulate the controller. The effect of the controller on
      the contrast agent response is investigated for various control scenarios. This
      work demonstrates the feasibility of using a nonlinear control system to modulate
      the dynamic response of ultrasound contrast agents, but highlights the need for
      improved feedback mechanisms and control input methods. Possible applications of
      the nonlinear control system to contrast agents illustrated in this work include
      radius stabilization in the presence of an acoustic wave, radial growth and
      subsequent collapse, and generation of periodic radial oscillations while a
      contrast agent is within an acoustic forcing regime known to cause a chaotic
      response. 

PMID- 23862801
TI  - Time-selective windowing technique in free-field microphone reciprocity
      calibration.
AB  - Time-selective windowing techniques, which effectively remove multi-path noise,
      have been widely utilized for reciprocity calibration of microphone there are
      still limitations imposed by overlapping signals, particularly at low frequencies
      and for high Q microphones. Based on a fast Fourier transform analysis, the
      leakage due to a limited frequency range makes the overlap problem worse, not be
      perfectly separated. Instead of using conventional low-pass filters that are
      designed to have a flat response in the frequency range of interest, in this
      study, a filter with a Dolph-Chebyshev window shape was proposed because it has
      low sidelobe levels. After removing multi-path noise with a time-selective
      window, an inverse filter should be applied to compensate for distortion created
      by the applied filter. The method suggested in this paper extends the possible
      frequency range of free-field reciprocity calibration to frequencies below 2 kHz.

PMID- 23862802
TI  - Two parabolic equations for propagation in layered poro-elastic media.
AB  - Parabolic equation methods for fluid and elastic media are extended to layered
      poro-elastic media, including some shallow-water sediments. A previous parabolic
      equation solution for one model of range-independent poro-elastic media [Collins
      et al., J. Acoust. Soc. Am. 98, 1645-1656 (1995)] does not produce accurate
      solutions for environments with multiple poro-elastic layers. First, a dependent
      variable formulation for parabolic equations used with elastic media is
      generalized to layered poro-elastic media. An improvement in accuracy is obtained
      using a second dependent-variable formulation that conserves dependent variables
      across interfaces between horizontally stratified layers. Furthermore, this
      formulation expresses conditions at interfaces using no depth derivatives higher
      than first order. This feature should aid in treating range dependence because
      convenient matching across interfaces is possible with discretized derivatives of
      first order in contrast to second order. 

PMID- 23862803
TI  - Effects of secondary loudspeaker properties on broadband feedforward active duct
      noise control.
AB  - Dependence of the performance of feedforward active duct noise control on
      secondary loudspeaker parameters is investigated. Noise reduction performance can
      be improved if the force factor of the secondary loudspeaker is higher. For
      example, broadband noise reduction improvement up to 1.6 dB is predicted by
      increasing the force factor by 50%. In addition, a secondary loudspeaker with a
      larger force factor was found to have quicker convergence in the adaptive
      algorithm in experiment. In simulations, noise reduction is improved in using an
      adaptive algorithm by using a secondary loudspeaker with a heavier moving mass.
      It is predicted that an extra broadband noise reduction of more than 7 dB can be
      gained using an adaptive filter if the force factor, moving mass and coil
      inductance of a commercially available loudspeaker are doubled. Methods to
      increase the force factor beyond those of commercially available loudspeakers are
      proposed. 

PMID- 23862804
TI  - Quantifying scattered sound energy from a single tree by means of reverberation
      time.
AB  - Trees in urban spaces surrounded by buildings may be effective in dispersing
      sound energy, and this could affect sound level distribution and street canyon
      reverberation. To quantify this effect of trees with a view to including it in
      numerical predictions, this paper examines sound scattering from a single tree in
      open field by means of reverberation time (RT). Five trees of different species
      and crown sizes were considered. The influence of ground condition, receiver
      height, crown size and shape, foliage condition, and source-receiver angle and
      distance has been assessed. The results show that RT20 is proportional to the
      tree crown size, which is the most important factor. The maximum RT20 measured
      was 0.28 s at 4000 Hz for the studied trees when in leaf (with foliage). The
      presence of leaves increased RT20 at high frequencies, typically by 0.08 s at
      4000 Hz. It was also demonstrated that the source-receiver angle can affect the
      characteristics of decay curves significantly. With increasing source-receiver
      distance within 40 m, RT20 was slightly changed. It was shown that ground
      condition and receiver height affect the decay curves, especially at low and mid
      frequencies, where sound scattering is of relatively limited importance. 

PMID- 23862806
TI  - Numerical methodologies for optimizing and predicting the low frequency behavior
      of anechoic chambers.
AB  - This paper presents a description of the use of simplified numerical
      methodologies for the optimization of the low cut-off frequency of anechoic and
      hemi-anechoic chambers. The anechoic chamber is modeled as a cavity with proper
      surface impedance boundary conditions. First, the shape of the wedges is
      optimized by means of a minimization-based procedure of a finite element model of
      such elements in a "virtual" impedance tube for a plane wave field. An equivalent
      surface impedance of the wedges is determined from those data. An analytical
      procedure is then used to determine the complex reflection coefficient for
      spherical waves at oblique incidence. Finally, a complex image source approach is
      used to predict the sound field within the chamber. The methodology is applied to
      two anechoic chambers and the results are compared in terms of sound decay along
      fixed directions and surface pressure distributions. 

PMID- 23862807
TI  - Determination of the complex acoustic scattering matrix of a right-angled duct.
AB  - A method for determining the complete higher-order scattering matrix of an
      acoustic discontinuity is developed. The method is demonstrated for a right
      angled waveguide bend, and the magnitude and phase of the reflection and
      transmission coefficients are extracted precisely. The procedure is
      straightforward and based on the solutions to the Helmholtz equation by the
      finite element method (FEM). The consistency of the scattering coefficients found
      by this method is verified by their properties of symmetry, and their accuracy is
      established by the conservation of energy. The reliability of the new technique
      is further proved by means of an arbitrary sound source and by comparing the
      direct FEM response to the reflection matrix calculation. Some features of the
      scattering matrix as a function of frequency are surprising, such as the steps
      and reversion of the phase evolution or the complete loss of transmission of the
      incoming wave. The methodology detailed in this paper can be extended to other
      multiport junctions, such as T-junctions or size discontinuities in ducts. 

PMID- 23862805
TI  - Impulse source versus dodecahedral loudspeaker for measuring parameters derived
      from the impulse response in room acoustics.
AB  - This study investigates the performance of dodecahedral and impulse sources when
      measuring acoustic parameters in enclosures according to ISO 3382-1 [Acoustics
      Measurement of room acoustic parameters. Part 1: Performance spaces
      (International Organization for Standardization, Geneva, Switzerland, 2009)]. In
      general, methods using speakers as a sound source are limited by their frequency
      response and directivity. On the other hand, getting impulse responses from
      impulse sources typically involves a lack of repeatability, and it is usually
      necessary to average several measurements for each position. Through experiments
      in different auditoriums that recreate typical situations in which the
      measurement standard is applied, it is found that using impulse sources leads to
      greater variation in the results, especially at low frequencies. However, this
      prevents subsequent dispersions due to variables that this technique does not
      require, such as the orientation of the emitting source. These dispersions may be
      relevant at high frequencies exceeding the established tolerance criteria for
      certain parameters. Finally, a new descriptor for dodecahedral sources reflecting
      the influence their lack of omnidirectionality produces on measuring acoustic
      parameters is proposed. 

PMID- 23862808
TI  - Enhanced multistatic active sonar signal processing.
AB  - Multistatic active sonar systems involve the transmission and reception of
      multiple probing sequences and can achieve significantly enhanced performance of
      target detection and localization through exploiting spatial diversity. This
      paper mainly focuses on two signal processing aspects of such systems, namely,
      enhanced range-Doppler imaging and improved target parameter estimation. The main
      contributions of this paper are (1) a hybrid dense-sparse method is proposed to
      generate range-Doppler images with both low sidelobe levels and high accuracy;
      (2) a generalized K-Means clustering (GKC) method for target association is
      developed to associate the range measurements from different transmitter-receiver
      pairs, which is actually a range fitting procedure; (3) the extended invariance
      principle-based weighted least-squares method is developed for accurate target
      position and velocity estimation. The effectiveness of the proposed multistatic
      active sonar signal processing techniques is verified using numerical examples. 

PMID- 23862809
TI  - Broadband synthetic aperture geoacoustic inversion.
AB  - A typical geoacoustic inversion procedure involves powerful source transmissions
      received on a large-aperture receiver array. A more practical approach is to use
      a single moving source and/or receiver in a low signal to noise ratio (SNR)
      setting. This paper uses single-receiver, broadband, frequency coherent matched
      field inversion and exploits coherently repeated transmissions to improve
      estimation of the geoacoustic parameters. The long observation time creates a
      synthetic aperture due to relative source-receiver motion. This approach is
      illustrated by studying the transmission of multiple linear frequency modulated
      (LFM) pulses which results in a multi-tonal comb spectrum that is Doppler
      sensitive. To correlate well with the measured field across a receiver trajectory
      and to incorporate transmission from a source trajectory, waveguide Doppler and
      normal mode theory is applied. The method is demonstrated with low SNR, 100-900
      Hz LFM pulse data from the Shallow Water 2006 experiment. 

PMID- 23862810
TI  - Evaluation of a separation method for source identification in small spaces.
AB  - This paper investigates the efficiency of a field separation method for the
      identification of sound sources in small and non-anechoic spaces. When performing
      measurements in such environments, the acquired data contain information from the
      direct field radiated by the source of interest and reflections from walls. To
      get rid of the unwanted contributions and assess the field radiated by the source
      of interest, a field separation method is used. Acoustic data (pressure or
      velocity) are then measured on a hemispheric array whose base is laying on the
      surface of interest. Then, by using spherical harmonic expansions, contributions
      from outgoing and incoming waves can be separated if the impedance of the tested
      surface is high enough. Depending on the probe type, different implementations of
      the separation method are numerically compared. In addition, the influence of the
      walls' reflection coefficient is studied. Finally, measurements are performed
      using an array made-up of 36 p-p probes. Results obtained in a car trunk mock-up
      with controlled sources are first presented before reporting results measured in
      a real car running on a roller bench. 

PMID- 23862811
TI  - Wideband energy reflectance measurements: effects of negative middle ear pressure
      and application of a pressure compensation procedure.
AB  - The wideband energy reflectance (ER) technique has become popular as a tool for
      evaluating middle ear function. Negative middle ear pressure (MEP) is a prevalent
      form of middle ear dysfunction, which may impact application of ER measurements
      in differential diagnosis. A negative MEP may be countervailed by application of
      an equivalent negative ear canal pressure. The present study examined ER in the
      same ears under normal and experimentally induced negative MEP conditions. Thirty
      five subjects produced at least one negative MEP each (-40 to -225 daPa).
      Negative MEP significantly altered ER in a frequency-specific manner that varied
      with MEP magnitude. ER increased for low- to mid-frequencies with the largest
      change (~0.20 to 0.40) occurring between 1 and 1.5 kHz. ER decreased for
      frequencies above 3 kHz with the largest change (~-0.10 to -0.25) observed
      between 4.5 and 5.5 kHz. Magnitude of changes increased as MEP became more
      negative, as did the frequencies at which maximum changes occurred, and the
      frequency at which enhancement transitioned to reduction. Ear canal pressure
      compensation restored ER to near baseline values. This suggests that the
      compensation procedure adequately mitigates the effects of negative MEP on ER.
      Theoretical issues and clinical implications are discussed.

PMID- 23862812
TI  - Time-domain demonstration of distributed distortion-product otoacoustic emission
      components.
AB  - Distortion-product otoacoustic emissions (DPOAEs) were measured in rabbits as
      time waveforms by employing a phase-rotation technique to cancel all components
      in the final average, except the 2f1-f2 DPOAE. Subsequent filtering allowed the
      DPOAE waveform to be clearly visualized in the time domain. In most conditions,
      f2 was turned off for 6 ms, which produced a gap so that the DPOAE was no longer
      generated. These procedures allowed the DPOAE onset as well as the decay during
      the gap to be observed in the time domain. DPOAEs were collected with L1 = L2 =
      65-dB sound pressure level primary-tone levels for f2/f1 ratios from 1.25 to 1.01
      in 0.02 steps. Findings included the appearance of complex onsets and decays for
      the DPOAE time waveforms as the f2/f1 ratio was decreased and the DPOAE level was
      reduced. These complexities were unaffected by interference tones (ITs) near the
      DPOAE frequency place (fdp), but could be removed by ITs presented above f2,
      which also increased DPOAE levels. Similar outcomes were observed when DPOAEs
      were measured at a sharp notch in the DPOAE level as a function of the f2 primary
      tone frequency, i.e., DP-gram. Both findings were consistent with the hypothesis
      that the DPOAE-ratio function, and some notches in the DP-gram, are caused by
      interactions of distributed DPOAE components with unique phases. 

PMID- 23862813
TI  - Measuring stimulus-frequency otoacoustic emissions using swept tones.
AB  - Although stimulus-frequency otoacoustic emissions (SFOAEs) offer compelling
      advantages as noninvasive probes of cochlear function, they remain underutilized
      compared to other evoked emission types, such as distortion-products (DPOAEs),
      whose measurement methods are less complex and time-consuming. Motivated by
      similar advances in the measurement of DPOAEs, this paper develops and
      characterizes a more efficient SFOAE measurement paradigm based on swept tones.
      In contrast to standard SFOAE measurement methods, in which the emissions are
      measured in the sinusoidal steady-state using discrete tones of well defined
      frequency, the swept-tone method sweeps rapidly across frequency (typically at
      rates of 1 Hz/ms or greater) using a chirp-like stimulus. Measurements obtained
      using both swept- and discrete-tone methods in an interleaved suppression
      paradigm demonstrate that the two methods of measuring SFOAEs yield nearly
      equivalent results, the differences between them being comparable to the run-to
      run variability encountered using either method alone. The match appears robust
      to variations in measurement parameters, such as sweep rate and direction. The
      near equivalence of the SFOAEs obtained using the two measurement methods enables
      the interpretation of swept-tone SFOAEs within existing theoretical frameworks.
      Furthermore, the data demonstrate that SFOAE phase-gradient delays-including
      their large and irregular fluctuations across frequency-reflect actual physical
      time delays at different frequencies, showing that the physical emission latency,
      not merely the phase gradient, is inherently irregular. 

PMID- 23862814
TI  - Relation of distortion-product otoacoustic emission input-output functions to
      loudness.
AB  - The aim of this study is to further explore the relationship between distortion
      product otoacoustic emission (DPOAE) measurements and categorical loudness
      scaling (CLS) measurements using multiple linear regression (MLR) analysis.
      Recently, Thorson et al. [J. Acoust. Soc. Am. 131, 1282-1295 (2012)] obtained
      predictions of CLS loudness ratings from DPOAE input/output (I/O) functions using
      MLR analysis. The present study extends that work by (1) considering two
      different (and potentially improved) MLR models, one for predicting loudness
      rating at specified input level and the other for predicting the input level for
      each loudness category and (2) validating the new models' predictions using an
      independent set of data. Strong correlations were obtained between predicted and
      measured data during the validation process with overall root-mean-square errors
      in the range 10.43-16.78 dB for the prediction of CLS input level, supporting the
      view that DPOAE I/O measurements can predict CLS loudness ratings and input
      levels, and thus may be useful for fitting hearing aids.

PMID- 23862815
TI  - A comparison of spectral magnitude and phase-locking value analyses of the
      frequency-following response to complex tones.
AB  - Two experiments, both presenting diotic, harmonic tone complexes (100 Hz
      fundamental), were conducted to explore the envelope-related component of the
      frequency-following response (FFRENV), a measure of synchronous, subcortical
      neural activity evoked by a periodic acoustic input. Experiment 1 directly
      compared two common analysis methods, computing the magnitude spectrum and the
      phase-locking value (PLV). Bootstrapping identified which FFRENV frequency
      components were statistically above the noise floor for each metric and
      quantified the statistical power of the approaches. Across listeners and
      conditions, the two methods produced highly correlated results. However, PLV
      analysis required fewer processing stages to produce readily interpretable
      results. Moreover, at the fundamental frequency of the input, PLVs were farther
      above the metric's noise floor than spectral magnitudes. Having established the
      advantages of PLV analysis, the efficacy of the approach was further demonstrated
      by investigating how different acoustic frequencies contribute to FFRENV,
      analyzing responses to complex tones composed of different acoustic harmonics of
      100 Hz (Experiment 2). Results show that the FFRENV response is dominated by
      peripheral auditory channels responding to unresolved harmonics, although low
      frequency channels driven by resolved harmonics also contribute. These results
      demonstrate the utility of the PLV for quantifying the strength of FFRENV across
      conditions. 

PMID- 23862816
TI  - Predictions of diotic tone-in-noise detection based on a nonlinear optimal
      combination of energy, envelope, and fine-structure cues.
AB  - Tone-in-noise detection has been studied for decades; however, it is not
      completely understood what cue or cues are used by listeners for this task. Model
      predictions based on energy in the critical band are generally more successful
      than those based on temporal cues, except when the energy cue is not available.
      Nevertheless, neither energy nor temporal cues can explain the predictable
      variance for all listeners. In this study, it was hypothesized that better
      predictions of listeners' detection performance could be obtained using a
      nonlinear combination of energy and temporal cues, even when the energy cue was
      not available. The combination of different cues was achieved using the
      logarithmic likelihood-ratio test (LRT), an optimal detector in signal detection
      theory. A nonlinear LRT-based combination of cues was proposed, given that the
      cues have Gaussian distributions and the covariance matrices of cue values from
      noise-alone and tone-plus-noise conditions are different. Predictions of
      listeners' detection performance for three different sets of reproducible noises
      were computed with the proposed model. Results showed that predictions for hit
      rates approached the predictable variance for all three datasets, even when an
      energy cue was not available. 

PMID- 23862817
TI  - Time-frequency integration characteristics of hearing are optimized for
      perception of speech-like acoustic patterns.
AB  - Several psychoacoustic phenomena such as loudness perception, absolute thresholds
      of hearing, and perceptual grouping in time are affected by temporal integration
      of the signal in the auditory system. Similarly, the frequency resolution of the
      hearing system, often expressed in terms of critical bands, implies signal
      integration across neighboring frequencies. Although progress has been made in
      understanding the neurophysiological mechanisms behind these processes, the
      underlying reasons for the observed integration characteristics have remained
      poorly understood. The current work proposes that the temporal and spectral
      integration are a result of a system optimized for pattern detection from
      ecologically relevant acoustic inputs. This argument is supported by a simulation
      where the average time-frequency structure of speech that is derived from a large
      set of speech signals shows a good match to the time-frequency characteristics of
      the human auditory system. The results also suggest that the observed integration
      characteristics are learnable from acoustic inputs of the auditory environment
      using a Hebbian-like learning rule. 

PMID- 23862818
TI  - A precedence effect model to simulate localization dominance using an adaptive,
      stimulus parameter-based inhibition process.
AB  - A number of precedence-effect models have been developed to simulate the robust
      localization performance of humans in reverberant conditions. Although they are
      able to reduce reverberant information for many conditions, they tend to fail for
      ongoing stimuli with truncated on/offsets, a condition human listeners master
      when localizing a sound source in the presence of a reflection, according to a
      study by Dizon and Colburn [J. Acoust. Soc. Am. 119, 2947-2964 (2006)]. This
      paper presents a solution for this condition by using an autocorrelation
      mechanism to estimate the delay and amplitude ratio between the leading and
      lagging signals. An inverse filter is then used to eliminate the lag signal,
      before it is localized with a standard localization algorithm. The current
      algorithm can operate on top of a basic model of the auditory periphery
      (gammatone filter bank, half-wave rectification) to simulate psychoacoustic data
      by Braasch et al. [Acoust. Sci. Tech. 24, 293-303 (2003)] and Dizon and Colburn.
      The model performs robustly with these on/offset truncated and interaural level
      difference based stimuli and is able to demonstrate the Haas effect. 

PMID- 23862819
TI  - A multi-resolution envelope-power based model for speech intelligibility.
AB  - The speech-based envelope power spectrum model (sEPSM) presented by Jorgensen and
      Dau [(2011). J. Acoust. Soc. Am. 130, 1475-1487] estimates the envelope power
      signal-to-noise ratio (SNRenv) after modulation-frequency selective processing.
      Changes in this metric were shown to account well for changes of speech
      intelligibility for normal-hearing listeners in conditions with additive
      stationary noise, reverberation, and nonlinear processing with spectral
      subtraction. In the latter condition, the standardized speech transmission index
      [(2003). IEC 60268-16] fails. However, the sEPSM is limited to conditions with
      stationary interferers, due to the long-term integration of the envelope power,
      and cannot account for increased intelligibility typically obtained with
      fluctuating maskers. Here, a multi-resolution version of the sEPSM is presented
      where the SNRenv is estimated in temporal segments with a modulation-filter
      dependent duration. The multi-resolution sEPSM is demonstrated to account for
      intelligibility obtained in conditions with stationary and fluctuating
      interferers, and noisy speech distorted by reverberation or spectral subtraction.
      The results support the hypothesis that the SNRenv is a powerful objective metric
      for speech intelligibility prediction.

PMID- 23862820
TI  - Identification of stimulus cues in narrow-band tone-in-noise detection using
      sparse observer models.
AB  - The classical psychophysical paradigm of narrow-band tone-in-noise (TiN)
      detection has been under investigation for more than 70 years, yet no conclusive
      answer has been given as to which auditory stimulus features listeners rely on.
      Here, individual observer models were fit to a large trial-by-trial behavioral
      data set using a modern statistical analysis procedure. Relative perceptual
      weights were estimated for a set of auditory features including sound energy,
      representations of the spectra as well as summary statistics of both fine
      structure and envelope. The fitted models captured the behavior of all listeners
      on a single-trial level. The estimated perceptual weights were stable across
      signal levels. They suggest that responses of observers depended on stimulus
      energy, though that cue was not always dominant, as well as on band-pass
      detectors applied to the fine structure spectrum. A subset of the observers
      exhibited an additional dependence on sound envelope which was best captured by
      two envelope descriptors: average slope and extrema count. For some listeners, a
      concurrent analysis of sequential dependencies showed interactions between the
      current and several preceding decisions. There was no unique answer regarding the
      strategy individual listeners employ during TiN detection, and implications
      thereof are discussed. 

PMID- 23862821
TI  - The detection of repetitions in noise before and after perceptual learning.
AB  - In noise repetition-detection tasks, listeners have to distinguish trials of
      continuously running noise from trials in which noise tokens are repeated in a
      cyclic manner. Recently, it has been shown that using the exact same noise token
      across several trials ("reference noise") facilitates the detection of
      repetitions for this token [Agus et al. (2010). Neuron 66, 610-618]. This was
      attributed to perceptual learning. Here, the nature of the learning was
      investigated. In experiment 1, reference noise tokens were embedded in trials
      with or without cyclic presentation. Naive listeners reported repetitions in both
      cases, thus responding to the reference noise even in the absence of an actual
      repetition. Experiment 2, with the same listeners, showed a similar pattern of
      results even after the design of the experiment was made explicit, ruling out a
      misunderstanding of the task. Finally, in experiment 3, listeners reported
      repetitions in trials containing the reference noise, even before ever hearing it
      presented cyclically. The results show that listeners were able to learn and
      recognize noise tokens in the absence of an immediate repetition. Moreover, the
      learning mandatorily interfered with listeners' ability to detect repetitions. It
      is concluded that salient perceptual changes accompany the learning of noise. 

PMID- 23862822
TI  - Perceptual constancy in auditory perception of distance to railway tracks.
AB  - Distance to a sound source can be accurately estimated solely from auditory
      information. With a sound source such as a train that is passing by at a
      relatively large distance, the most important auditory information for the
      listener for estimating its distance consists of the intensity of the sound,
      spectral changes in the sound caused by air absorption, and the motion-induced
      rate of change of intensity. However, these cues are relative because prior
      information/experience of the sound source-its source power, its spectrum and the
      typical speed at which it moves-is required for such distance estimates. This
      paper describes two listening experiments that allow investigation of further
      prior contextual information taken into account by listeners-viz., whether they
      are indoors or outdoors. Asked to estimate the distance to the track of a
      railway, it is shown that listeners assessing sounds heard inside the dwelling
      based their distance estimates on the expected train passby sound level outdoors
      rather than on the passby sound level actually experienced indoors. This form of
      perceptual constancy may have consequences for the assessment of annoyance caused
      by railway noise. 

PMID- 23862823
TI  - Binaural hearing ability with mastoid applied bilateral bone conduction
      stimulation in normal hearing subjects.
AB  - The ability to use binaural cues when stimulation was by bilaterally applied bone
      conduction (BC) transducers was investigated in 20 normal hearing participants.
      The results with BC stimulation were compared with normal air conduction (AC)
      stimulation through earphones. The binaural hearing ability was tested by spatial
      release from masking, binaural intelligibility level difference (BILD), binaural
      masking level difference (BMLD) using chirp stimulation, and test of the
      precedence effect. In all tests, the participants revealed a benefit of bilateral
      BC stimulation indicating use of binaural cues. In the speech based tests, the
      binaural benefit for BC stimulation was approximately half that with AC
      stimulation. For the BC BMLD test with chirp stimulation, there were indications
      of superposition of the ipsilateral and contralateral pathways at the cochlear
      level affecting the results. The precedence effect test indicated significantly
      worse results for BC stimulation than for AC stimulation with low-frequency
      stimulation while they were close for high-frequency stimulation; broad-band
      stimulation gave results that were slightly worse than the high-frequency
      results. 

PMID- 23862824
TI  - The effect of overall level on sensitivity to interaural differences of time and
      level at high frequencies.
AB  - For high-frequency complex stimuli, detection thresholds for envelope-based
      interaural time differences (ITDs) decrease with overall level. Substantial
      heterogeneity is, however, evident among the findings concerning the rate at
      which thresholds decline with level. This study investigated factors affecting
      the influence of overall level on threshold ITDs. Thresholds were measured as a
      function of overall level for 4-kHz-centered "targets" in three experiments
      focusing, respectively, on stimulus-type (sinusoidally amplitude-modulated or
      "transposed" tones), modulation frequency, and details concerning low-pass noise
      used to mask low-frequency distortion products. Results indicated that (1) log
      ITD thresholds decreased linearly with overall level; (2) slopes relating log-ITD
      thresholds to level did not depend significantly on stimulus type; (3) lower
      modulation frequencies produced greater dependencies of thresholds on overall
      level than did higher modulation frequencies; (4) the effect of overall level on
      threshold-ITDs was independent of the interaural configuration and levels of the
      low-pass noise maskers tested; (5) synchronously gating the low-pass noise and
      target produced a greater dependency of thresholds on the overall level of the
      target than did continuous or temporally "fringed" presentation of the noise. A
      fourth experiment showed that threshold interaural level differences were
      somewhat less affected by changes in overall level than were threshold ITDs. 

PMID- 23862825
TI  - Polarity effects on place pitch and loudness for three cochlear-implant designs
      and at different cochlear sites.
AB  - Users of Advanced Bionics, MedEl, and Cochlear Corp. implants balanced the
      loudness of trains of asymmetric pulses of opposite polarities presented in
      monopolar mode. For the Advanced Bionics and MedEl users the pulses were
      triphasic and consisted of a 32-MUs central phase flanked by two 32-MUs phases of
      opposite polarity and half the amplitude. The central phase was either anodic (TP
      A) or cathodic (TP-C). For the Cochlear Corp. users, pulses consisted of two 32
      MUs phases of the same polarity separated by an 8-MUs gap, flanked by two 32-MUs
      phases of the opposite polarity, each of which was separated from the central
      portion by a 58-MUs gap. The central portion of these quadraphasic pulses was
      either anodic (QP-A) or cathodic (QP-C), and all phases had the same amplitude.
      The current needed to achieve matched loudness was lower for the anodic than for
      the cathodic stimuli. This polarity effect was similar across all electrode
      locations studied, including the most apical electrode of the MedEl device which
      stimulates the very apex of the cochlea. In addition, when quadraphasic pulses
      were presented in bipolar mode, listeners reported hearing a lower pitch when the
      central portion was anodic at the more apical, than at the more basal, electrode.
      The results replicate previous reports that, unlike the results of most animal
      studies, human cochlear implant listeners are more sensitive to anodic than to
      cathodic currents, and extend those findings to a wider range of cochlear sites,
      implant types, and pulse shapes. 

PMID- 23862826
TI  - An investigation of articulatory setting using real-time magnetic resonance
      imaging.
AB  - This paper presents an automatic procedure to analyze articulatory setting in
      speech production using real-time magnetic resonance imaging of the moving human
      vocal tract. The procedure extracts frames corresponding to inter-speech pauses,
      speech-ready intervals and absolute rest intervals from magnetic resonance
      imaging sequences of read and spontaneous speech elicited from five healthy
      speakers of American English and uses automatically extracted image features to
      quantify vocal tract posture during these intervals. Statistical analyses show
      significant differences between vocal tract postures adopted during inter-speech
      pauses and those at absolute rest before speech; the latter also exhibits a
      greater variability in the adopted postures. In addition, the articulatory
      settings adopted during inter-speech pauses in read and spontaneous speech are
      distinct. The results suggest that adopted vocal tract postures differ on average
      during rest positions, ready positions and inter-speech pauses, and might, in
      that order, involve an increasing degree of active control by the cognitive
      speech planning mechanism. 

PMID- 23862827
TI  - Stress-meter alignment in French vocal music.
AB  - Previous research has shown disagreement regarding the nature of stress in
      French. Some have maintained that French has lexical stress on the final syllable
      of each word; others have argued that French has no lexical stress, only phrasal
      stress. A possible source of evidence on this issue is vocal music. In languages
      with lexical stress, such as English, it is well known that stressed syllables
      tend to occur at "strong" positions in the musical meter (some evidence will be
      presented supporting this view). A corpus analysis was performed to investigate
      the degree of stress-meter alignment in French songs. The analysis showed that
      (excluding syllables at the ends of lines) the final syllables of polysyllabic
      words tend to occur at stronger metrical positions than non-final syllables of
      those words; it also showed that monosyllabic content words tend to occur at
      stronger positions than monosyllabic function words. While conflicts between
      stress and meter are much more common in French than in English vocal music,
      these results suggest that French poets and composers recognized distinctions of
      stress between syllables of polysyllabic words and between monosyllabic content
      and function words. 

PMID- 23862828
TI  - Measuring body layer vibration of vocal folds by high-frame-rate ultrasound
      synchronized with a modified electroglottograph.
AB  - The body-cover concept suggests that the vibration of body layer is an
      indispensable component of vocal fold vibration. To quantify this vibration, a
      synchronized system composed of a high-frame-rate ultrasound and a modified
      electroglottograph (EGG) was employed in this paper to simultaneously image the
      body layer vibration and record the vocal fold vibration phase information during
      natural phonations. After data acquisition, the displacements of in vivo body
      layer vibrations were measured from the ultrasonic radio frequency data, and the
      temporal reconstruction method was used to enhance the measurement accuracy.
      Results showed that the modified EGG, the waveform and characteristic points of
      which were identical to the conventional EGG, resolved the position conflict
      between the ultrasound transducer and EGG electrodes. The location and range of
      the vibrating body layer in the estimated displacement image were more clear and
      discernible than in the ultrasonic B-mode image. Quantitative analysis for
      vibration features of the body layer demonstrated that the body layer moved as a
      unit in the superior-inferior direction during the phonation of normal chest
      registers. 

PMID- 23862829
TI  - Articulatory overlap as a function of voicing in French and German consonant
      clusters.
AB  - The effects of laryngeal specification on the timing of supra-laryngeal
      articulations have so far received little attention. Previous research has shown
      that German-but not French-mixed-voicing clusters are produced with less
      articulatory overlap than phonologically fully voiced clusters. Articulatory and
      acoustic data of labial and velar stops as simple onsets and in stop + /l/
      clusters are examined to probe the causes for this cross-linguistic difference in
      the light of the different voicing implementations of French and German. The
      absence of overlap in German mixed-voicing clusters is attributed to the
      requirement of a time slot for the stop's aspiration phase. Since French does not
      commonly have aspirated stops, French clusters are expected to pattern with the
      voiced German clusters. The results confirm that voicing patterns established for
      simple onsets in the literature in terms of voice onset time of both German and
      French also obtain in clusters. Furthermore, the data show that contrary to the
      expectations French clusters pattern with German mixed-voicing clusters. This low
      degree of overlap in both voiceless and voiced French clusters indicates that
      overlap is restricted by aerodynamic requirements which result from the
      implementations of the voicing contrast. 

PMID- 23862830
TI  - The effect of prosodic weakening on the production and perception of trans
      consonantal vowel coarticulation in German.
AB  - The present study considers whether coarticulation in production and its
      relationship to categorization could provide a synchronic basis for the
      prevalence of sound change in unstressed syllables. The size of V2-on-V1
      coarticulation in the production of /pV1pV2l/ non-words (V1 = /U,Y/ and V2 = /e,
      o/) produced by German speakers and with stress falling either on the first or
      second syllable was compared with forced-choice perceptual categorization of
      resynthesized versions of these non-words. In speech production, /Y/ but not /U/
      was perturbed by anticipatory V2-on-V1 coarticulation. Stress had no influence on
      coarticulation but caused target undershoot in /U/. The same speakers compensated
      for coarticulation in perception: however, in the unstressed context the speakers
      compensated less and their diminished compensatory coarticulation was shown to be
      linked to /U/-undershoot. Taken together, these results point to a mismatch
      between coarticulation and categorization that is suggested as a possible source
      of sound change: whereas de-stressing did not affect V2-on-V1 coarticulation in
      production, it weakened V2's influence on perceptual /upsilon-Y/ categorization.
      The evidence that this mismatch is indirectly caused by stress-dependent
      reduction in /U/ that is unrelated to the V2-source of the coarticulation is also
      consistent with a model of sound change as non-teleological.

PMID- 23862831
TI  - Lexically guided retuning of visual phonetic categories.
AB  - Listeners retune the boundaries between phonetic categories to adjust to
      individual speakers' productions. Lexical information, for example, indicates
      what an unusual sound is supposed to be, and boundary retuning then enables the
      speaker's sound to be included in the appropriate auditory phonetic category. In
      this study, it was investigated whether lexical knowledge that is known to guide
      the retuning of auditory phonetic categories, can also retune visual phonetic
      categories. In Experiment 1, exposure to a visual idiosyncrasy in ambiguous
      audiovisually presented target words in a lexical decision task indeed resulted
      in retuning of the visual category boundary based on the disambiguating lexical
      context. In Experiment 2 it was tested whether lexical information retunes visual
      categories directly, or indirectly through the generalization from retuned
      auditory phonetic categories. Here, participants were exposed to auditory-only
      versions of the same ambiguous target words as in Experiment 1. Auditory phonetic
      categories were retuned by lexical knowledge, but no shifts were observed for the
      visual phonetic categories. Lexical knowledge can therefore guide retuning of
      visual phonetic categories, but lexically guided retuning of auditory phonetic
      categories is not generalized to visual categories. Rather, listeners adjust
      auditory and visual phonetic categories to talker idiosyncrasies separately. 

PMID- 23862832
TI  - Misperceptions of spoken words: data from a random sample of American English
      words.
AB  - This study reports a detailed analysis of incorrect responses from an open-set
      spoken word recognition experiment of 1428 words designed to be a random sample
      of the entire American English lexicon. The stimuli were presented in six-talker
      babble to 192 young, normal-hearing listeners at three signal-to-noise ratios (0,
      +5, and +10 dB). The results revealed several patterns: (1) errors tended to have
      a higher frequency of occurrence than did the corresponding target word, and
      frequency of occurrence of error responses was significantly correlated with
      target frequency of occurrence; (2) incorrect responses were close to the target
      words in terms of number of phonemes and syllables but had a mean edit distance
      of 3; (3) for syllables, substitutions were much more frequent than either
      deletions or additions; for phonemes, deletions were slightly more frequent than
      substitutions; both were more frequent than additions; and (4) for errors
      involving just a single segment, substitutions were more frequent than either
      deletions or additions. The raw data are being made available to other
      researchers as supplementary material to form the beginnings of a database of
      speech errors collected under controlled laboratory conditions. 

PMID- 23862833
TI  - Speech intelligibility in hospitals.
AB  - Effective communication between staff members is key to patient safety in
      hospitals. A variety of patient care activities including admittance, evaluation,
      and treatment rely on oral communication. Surprisingly, published information on
      speech intelligibility in hospitals is extremely limited. In this study, speech
      intelligibility measurements and occupant evaluations were conducted in 20 units
      of five different U.S. hospitals. A variety of unit types and locations were
      studied. Results show that overall, no unit had "good" intelligibility based on
      the speech intelligibility index (SII > 0.75) and several locations found to have
      "poor" intelligibility (SII < 0.45). Further, occupied spaces were found to have
      10%-15% lower SII than unoccupied spaces on average. Additionally, staff
      perception of communication problems at nurse stations was significantly
      correlated with SII ratings. In a targeted second phase, a unit treated with
      sound absorption had higher SII ratings for a larger percentage of time as
      compared to an identical untreated unit. Taken as a whole, the study provides an
      extensive baseline evaluation of speech intelligibility across a variety of
      hospitals and unit types, offers some evidence of the positive impact of
      absorption on intelligibility, and identifies areas for future research. 

PMID- 23862834
TI  - Unilateral and bilateral hearing aids, spatial release from masking and auditory
      acclimatization.
AB  - Spatial release from masking (SRM) was tested within the first week of fitting
      and after 12 weeks hearing aid use for unilateral and bilateral adult hearing aid
      users. A control group of experienced hearing aid users completed testing over a
      similar time frame. The main research aims were (1) to examine auditory
      acclimatization effects on SRM performance for unilateral and bilateral hearing
      aid users, (2) to examine whether hearing aid use, level of hearing loss, age or
      cognitive ability mediate acclimatization, and (3) to compare and contrast the
      outcome of unilateral versus bilateral aiding on SRM. Hearing aid users were
      tested with and without hearing aids, with SRM calculated as the 50% speech
      recognition threshold advantage when maskers and target are spatially separated
      at +/-90 degrees  azimuth to the listener compared to a co-located condition. The
      conclusions were (1) on average there was no improvement over time in familiar
      aided listening conditions, (2) there was large test-retest variability which may
      overshadow small average acclimatization effects; greater improvement was
      associated with better cognitive ability and younger age, but not associated with
      hearing aid use, and (3) overall, bilateral aids facilitated better SRM
      performance than unilateral aids. 

PMID- 23862835
TI  - Within-consonant perceptual differences in the hearing impaired ear.
AB  - The consonant recognition of 17 ears with sensorineural hearing loss is evaluated
      for 14 consonants /p, t, k, f, s, ?, b, d, g, v, z, 3, m, n/+/a/, under four
      speech-weighted noise conditions (0, 6, 12 dB SNR, quiet). One male and one
      female talker were chosen for each consonant, resulting in 28 total consonant
      vowel test tokens. For a given consonant, tokens by different talkers were
      observed to systematically differ, in both the robustness to noise and/or the
      resulting confusion groups. Such within-consonant token differences were observed
      for over 60% of the tested consonants and all HI ears. Only when HI responses are
      examined on an individual token basis does one find that the error may be limited
      to a small subset of tokens with confusion groups that are restricted to fewer
      than three confusions on average. Averaging different tokens of the same
      consonant can raise the entropy of a listener's responses (i.e., the size of the
      confusion group), causing the listener to appear to behave in a less systematic
      way. Quantifying these token differences provides insight into HI perception of
      speech under noisy conditions and characterizes each listener's hearing
      impairment.

PMID- 23862836
TI  - Recognition of accented and unaccented speech in different maskers by younger and
      older listeners.
AB  - This investigation examined the effect of accent of target talkers and background
      speech maskers on listeners' ability to use cues to separate speech from noise.
      Differences in accent may create a disparity in the relative timing between
      signal and background, and such timing cues may be used to separate the target
      talker from the background speech masker. However, the use of this cue could be
      reduced for older listeners with temporal processing deficits, especially those
      with hearing loss. Participants were younger and older listeners with normal
      hearing and older listeners with hearing loss. Stimuli were IEEE sentences
      recorded in English by male native speakers of English and Spanish. These
      sentences were presented in different maskers that included speech-modulated
      noise and background babbles varying in talker gender and accent. Signal-to-noise
      ratios corresponding to 50% correct performance were measured. Results indicate
      that a pronounced Spanish accent limits a listener's ability to take advantage of
      cues to speech segregation and that a difference in accentedness between the
      target talker and background masker may be a useful cue for speech segregation.
      Older hearing-impaired listeners performed poorly in all conditions with the
      accented talkers. 

PMID- 23862837
TI  - Speech rhythm analysis with decomposition of the amplitude envelope:
      characterizing rhythmic patterns within and across languages.
AB  - This study presents a method for analyzing speech rhythm using empirical mode
      decomposition of the speech amplitude envelope, which allows for extraction and
      quantification of syllabic- and supra-syllabic time-scale components of the
      envelope. The method of empirical mode decomposition of a vocalic energy
      amplitude envelope is illustrated in detail, and several types of rhythm metrics
      derived from this method are presented. Spontaneous speech extracted from the
      Buckeye Corpus is used to assess the effect of utterance length on metrics, and
      it is shown how metrics representing variability in the supra-syllabic time-scale
      components of the envelope can be used to identify stretches of speech with
      targeted rhythmic characteristics. Furthermore, the envelope-based metrics are
      used to characterize cross-linguistic differences in speech rhythm in the UC San
      Diego Speech Lab corpus of English, German, Greek, Italian, Korean, and Spanish
      speech elicited in read sentences, read passages, and spontaneous speech. The
      envelope-based metrics exhibit significant effects of language and elicitation
      method that argue for a nuanced view of cross-linguistic rhythm patterns. 

PMID- 23862839
TI  - Modeling and simulation of a grand piano.
AB  - A time-domain global modeling of a grand piano is presented. The string model
      includes internal losses, stiffness, and geometrical nonlinearity. The hammer
      string interaction is governed by a nonlinear dissipative compression force. The
      soundboard is modeled as a dissipative bidimensional orthotropic Reissner-Mindlin
      plate where the presence of ribs and bridges is treated as local heterogeneities.
      The coupling between strings and soundboard at the bridge allows the transmission
      of both transverse and longitudinal waves to the soundboard. The soundboard is
      coupled to the acoustic field, whereas all other parts of the structure are
      supposed to be perfectly rigid. The acoustic field is bounded artificially using
      perfectly matched layers. The discrete form of the equations is based on original
      energy preserving schemes. Artificial decoupling is achieved, through the use of
      Schur complements and Lagrange multipliers, so that each variable of the problem
      can be updated separately at each time step. The capability of the model is
      highlighted by series of simulations in the low, medium, and high register, and
      through comparisons with waveforms recorded on a Steinway D piano. Its ability to
      account for phantom partials and precursors, consecutive to string nonlinearity
      and inharmonicity, is particularly emphasized. 

PMID- 23862838
TI  - Evidence that the Lombard effect is frequency-specific in humans.
AB  - Recent perspectives suggest that the Lombard effect is an increase in the
      suprasegmental speech parameters of vocal intensity, duration, and fundamental
      frequency in the presence of noise. It has been viewed as a non-specific response
      to ambient noise, but this assumption has not been thoroughly tested. Two
      experiments using healthy adults measured intensity, duration, and F0 changes in
      broadband (0.2-20 kHz) and notched noise (0.05-4 kHz removed) during a picture
      naming task. The pilot experiment showed that broadband noise containing speech
      similar frequencies significantly increased intensity, duration, and F0 while
      notched noise, which removed the majority of speech-similar frequencies, had no
      effect. The main experiment added bandpass noise (0.05-4.0 kHz) which contained a
      major portion of speech-similar frequencies and was the mirror image of the
      notched noise. Broadband and notched noise results were replicated. Bandpass
      noise increased intensity and duration, but to a lesser degree than did broadband
      noise, and had no effect on F0. Findings show that the Lombard effect is
      sensitive to frequencies vital for speech and is not a general response to any
      competing sound in the environment. Implications for suprasegmental control of
      speech are discussed. 

PMID- 23862840
TI  - Sparse and structured decomposition of audio signals on hybrid dictionaries using
      musical priors.
AB  - This paper investigates the use of musical priors for sparse expansion of audio
      signals of music, on an overcomplete dual-resolution dictionary taken from the
      union of two orthonormal bases that can describe both transient and tonal
      components of a music audio signal. More specifically, chord and metrical
      structure information are used to build a structured model that takes into
      account dependencies between coefficients of the decomposition, both for the
      tonal and for the transient layer. The denoising task application is used to
      provide a proof of concept of the proposed musical priors. Several configurations
      of the model are analyzed. Evaluation on monophonic and complex polyphonic
      excerpts of real music signals shows that the proposed approach provides results
      whose quality measured by the signal-to-noise ratio is competitive with state-of
      the-art approaches, and more coherent with the semantic content of the signal. A
      detailed analysis of the model in terms of sparsity and in terms of
      interpretability of the representation is also provided and shows that the model
      is capable of giving a relevant and legible representation of Western tonal music
      audio signals. 

PMID- 23862842
TI  - Geographic variation of whistles of the striped dolphin (Stenella coeruleoalba)
      within the Mediterranean Sea.
AB  - The striped dolphin is a cosmopolitan species distributed worldwide.
      Morphological and genetic studies strongly suggest that the Mediterranean and
      eastern North Atlantic populations are isolated from each other. The
      Mediterranean population is considered a distinct conservation unit by
      International Union for the Conservation of Nature experts, classified as
      "vulnerable." This study describes the geographical variation of the striped
      dolphin whistles within the Mediterranean Sea. Recordings were collected from
      1996 to 2003 throughout the basin, employing multiple platforms. Thirty-seven
      independent sightings with acoustic data collection were made, and 599 whistles
      were extracted and considered for statistical analysis. Whistle analysis enabled
      the identification of sub-populations of striped dolphins within the
      Mediterranean Sea. The acoustic diversity observed reflects the genetic
      differences recently found among striped dolphins inhabiting different
      Mediterranean regions. The results of this study support the hypothesis that gene
      flow reduction plays an important role in determining variation in whistle
      duration and frequency parameters, while ecological and social factors influence
      parameters of the modulation domains. The ability to acoustically identify
      distinct geographic sub-populations could provide a useful tool for the
      management of this protected species.

PMID- 23862841
TI  - The measurement of ultrasound backscattering from cell pellet biophantoms and
      tumors ex vivo.
AB  - Simple scattering media fit scattering model theories much better than more
      complex scattering media. Tissue is much more complex as an acoustic scattering
      media and to date there has not been an adequate scattering model that fits it
      well. Previous studies evaluated the scattering characteristics of simple media
      (grouping of cells at various number densities) and fit them to the concentric
      spheres scattering model theory. This study is to increase the complexity of the
      media to provide insight into the acoustic scattering characteristics of tissue,
      and specifically two tumor types. Complementing the data from the tumors is 100%
      volume fraction cell pellets of the same cell lines. Cell pellets and ex vivo
      tumors are scanned using high-frequency single-element transducers (9-105 MHz),
      and the attenuation and backscatter coefficient (BSC) are estimated. BSC
      comparisons are made between cell pellets and tumors. The results show that the
      4T1 (ATCC #CRL-2539) cell pellets and tumors have similar BSC characteristics,
      whereas the MAT (ATCC #CRL-1666) cell pellets and tumors have significantly
      different BSC characteristics. Factors that yield such differences are explored.
      Also, the fluid-filled sphere and the concentric spheres models are evaluated
      against the BSC characteristics, demonstrating that further work is required. 

PMID- 23862843
TI  - Source levels of social sounds in migrating humpback whales (Megaptera
      novaeangliae).
AB  - The source level of an animal sound is important in communication, since it
      affects the distance over which the sound is audible. Several measurements of
      source levels of whale sounds have been reported, but the accuracy of many is
      limited because the distance to the source and the acoustic transmission loss
      were estimated rather than measured. This paper presents measurements of source
      levels of social sounds (surface-generated and vocal sounds) of humpback whales
      from a sample of 998 sounds recorded from 49 migrating humpback whale groups.
      Sources were localized using a wide baseline five hydrophone array and
      transmission loss was measured for the site. Social vocalization source levels
      were found to range from 123 to 183 dB re 1 MUPa @ 1 m with a median of 158 dB re
      1 MUPa @ 1 m. Source levels of surface-generated social sounds ("breaches" and
      "slaps") were narrower in range (133 to 171 dB re 1 MUPa @ 1 m) but slightly
      higher in level (median of 162 dB re 1 MUPa @ 1 m) compared to vocalizations. The
      data suggest that group composition has an effect on group vocalization source
      levels in that singletons and mother-calf-singing escort groups tend to vocalize
      at higher levels compared to other group compositions.

PMID- 23862881
TI  - Introduction to the special issue on soundscapes.

PMID- 23862882
TI  - Respondents' answers to community attitudinal surveys represent impressions of
      soundscapes and not merely reactions to the physical noise.
AB  - Noise dose as a sole independent variable accounts only for less than half of the
      variance in community response data. Non-acoustic factors, such as attitude to
      the noise source identified by Job [(1988). J. Acoust. Soc. Am. 83(3), 991-1001]
      and others, reduce the unexplained variance. This paper suggests that non
      acoustic factors reflect the context in which the sonic environment is perceived;
      hence, these factors constitute the judgments of a soundscape. Fidell et al.
      [(2011). J. Acoust. Soc. Am. 130(2), 791-806] show that a "community tolerance
      level" (CTL) is a one-number, community-specific, independent variable that
      represents the aggregate influence on annoyance judgments of all non-acoustic
      influences. Taken together these findings suggest that: (i) CTL is a one-number
      quantification of a soundscape, and (ii) a soundscape can be quantified by a
      single, numeric variable. It follows, if one can predict or calculate the single
      numeric quantification of a soundscape, that number will be the CTL. These
      results can only be true for a soundscape judged on the basis of annoyance.
      Virtually no data exist for which the respondents even had the possibility to
      rate the sonic environment positively, i.e., pleasing, so the application of CTL
      to soundscapes judged positively is not clear. 

PMID- 23862884
TI  - Merging physical parameters and laboratory subjective ratings for the soundscape
      assessment of urban squares.
AB  - An experimental study was carried out in 20 squares in the center of Rome,
      covering a wide range of different uses, sonic environments, geometry, and
      architectural styles. Soundwalks along the perimeter of each square were
      performed during daylight and weekdays taking binaural and video recordings, as
      well as spot measurements of illuminance. The cluster analysis performed on the
      physical parameters, not only acoustic, provided two clusters that are in
      satisfactory agreement with the "a priori" classification. Applying the principal
      component analysis (PCA) to five physical parameters, two main components were
      obtained which might be associated to two environmental features, namely,
      "chaotic/calm" and "open/enclosed." On the basis of these two features, six
      squares were selected for the laboratory audio-video tests where 32 subjects took
      part filling in a questionnaire. The PCA performed on the subjective ratings on
      the sonic environment showed two main components which might be associated to two
      emotional meanings, namely, "calmness" and "vibrancy." The linear regression
      modeling between five objective parameters and the mean value of subjective
      ratings on chaotic/calm and enclosed/open attributes showed a good correlation.
      Notwithstanding these interesting results being limited to the specific data set,
      it is worth pointing out that the complexity of the soundscape quality assessment
      can be more comprehensively examined merging the field measurements of physical
      parameters with the subjective ratings provided by field and/or laboratory tests.

PMID- 23862883
TI  - The ecological context of soundscapes for children's blood pressure.
AB  - Although the majority of studies on community noise levels and children's
      physiological stress responses are positive, effect sizes vary considerably, and
      some studies do not confirm these effects. Employing a contextual perspective
      congruent with soundscapes, a carefully constructed sample of children (N = 115,
      M = 10.1 yr) living in households in relatively high (>60 dBA) or low (<50 dBA)
      noise areas created by proximity to major traffic arterials in Austria was
      reanalyzed. Several personal and environmental factors known to affect resting
      cardiovascular parameters measured under well-controlled, clinical conditions
      were incorporated into the analyses. Children with premature births and elevated
      chronic stress (i.e., overnight cortisol) were more susceptible to adverse blood
      pressure responses to road traffic noise. Residence in a multi-dwelling unit as
      well as standardized assessments of perceived quietness of the area did not
      modify the traffic noise impacts but each had its own, independent effect on
      resting blood pressure. A primary air pollutant associated with traffic volume
      (NO2) had no influence on any of these results. The scope of environmental noise
      assessment and management would benefit from incorporation of a more
      contextualized approach as suggested by the soundscape perspective.

PMID- 23862885
TI  - Application of a methodology for categorizing and differentiating urban
      soundscapes using acoustical descriptors and semantic-differential attributes.
AB  - A subjective and physical categorization of an ambient sound is the first step to
      evaluate the soundscape and provides a basis for designing or adapting this
      ambient sound to match people's expectations. For this reason, the main goal of
      this work is to develop a categorization and differentiation analysis of
      soundscapes on the basis of acoustical and perceptual variables. A hierarchical
      cluster analysis, using 15 semantic-differential attributes and acoustical
      descriptors to include an equivalent sound-pressure level, maximum-minimum sound
      pressure level, impulsiveness of the sound-pressure level, sound-pressure level
      time course, and spectral composition, was conducted to classify soundscapes into
      different typologies. This analysis identified 15 different soundscape
      typologies. Furthermore, based on a discriminant analysis the acoustical
      descriptors, the crest factor (impulsiveness of the sound-pressure level), and
      the sound level at 125 Hz were found to be the acoustical variables with the
      highest impact in the differentiation of the recognized types of soundscapes.
      Finally, to determine how the different soundscape typologies differed from each
      other, both subjectively and acoustically, a study was performed. 

PMID- 23862886
TI  - Soundwalk approach to identify urban soundscapes individually.
AB  - This study proposes a soundwalk procedure for evaluating urban soundscapes.
      Previous studies, which adopted soundwalk methodologies for investigating
      participants' responses to visual and acoustic environments, were analyzed
      considering type, evaluation position, measurement, and subjective assessment. An
      individual soundwalk procedure was then developed based on asking individual
      subjects to walk and select evaluation positions where they perceived any
      positive or negative characteristics of the urban soundscape. A case study was
      performed in urban spaces and the results were compared with those of the group
      soundwalk to validate the individual soundwalk procedure. Thirty subjects (15
      architects and 15 acousticians) participated in the soundwalk. During the
      soundwalk, the subjects selected a total of 196 positions, and those were
      classified into 4 groups. It was found that soundscape perceptions were dominated
      by acoustic comfort, visual images, and openness. It was also revealed that
      perceived elements of the acoustic environment and visual image differed across
      classified soundscape groups, and there was a difference between architects and
      acousticians in terms of how they described their impressions of the soundscape
      elements. The results show that the individual soundwalk procedure has advantages
      for measuring diverse subjective responses and for obtaining the perceived
      elements of the urban soundscape. 

PMID- 23862887
TI  - Measurements of acoustic environments for urban soundscapes: choice of
      homogeneous periods, optimization of durations, and selection of indicators.
AB  - In order to minimize the duration of acoustic measurements and to characterize
      homogeneous areas from a temporal point of view, a series of six location
      measurements was carried out continuously during three months in Paris. Around
      fifty thousand samples of 5-min, 10-min, 15-min, 20-min, 30-min, and 1-h duration
      measurements were extracted for each location. Each sample is characterized by
      eleven energy indicators and ten event descriptors. In this paper, analysis of a
      crossroad location is detailed. Through hierarchical ascendant classification and
      artificial neural networks classification, it is shown that four homogeneous
      periods can be detected: two during the night, one during the day, and one
      transition corresponding either to the awakening or to the moment when the city
      falls asleep. 10-min measurements are necessary to discriminate these time
      periods at the crossroad location. At the end of the paper, a comparison with the
      other locations shows that minimum duration states in between 10 and 20 min. The
      homogeneous periods are connected to the human activities and depend on the
      location. Energy indicators such as LAeq, LA10, or LA90 and event indicators are
      necessary to characterize the different clusters. 

PMID- 23862888
TI  - Assessment of noise measurements made with a continuous monitoring in time.
AB  - The World Health Organization has stated that hearing loss is one of the top 10
      health problems worldwide and that noise-induced hearing loss is the leading
      occupational disease. This work evaluated the noise exposure levels of several
      job categories for 24-h periods over 7 days to determine the contribution of each
      microenvironment to total noise exposure. The noise exposure levels of 47
      individuals were continuously measured using personal noise dosimeters in
      metropolitan Seoul, Korea. Participants ranged in age from 20 to 50 yr and
      represented eight occupational groups. Participants were asked to attach the
      noise dosimeters and complete a time-activity diary 24 h a day for 7 days. The
      average Leq 24 h,w among these individuals was 74 dBA, which ranged from 64 to 96
      dBA. The average Leq 24 h,w was highest for Korean traditional music apprentices,
      followed by heavy equipment operators, firefighters, service workers, office
      workers, industrial hygienists, graduate and undergraduate students, and
      housewives (89, 77, 76, 76, 75, 71, 71, and 71 dBA, respectively, p < 0.001). 38
      (80.9%) were exposed to noise levels greater than 70 dBA, which corresponds to
      the World Health Organization's exposure limit. 

PMID- 23862889
TI  - The perceived quality of soundscape in three urban parks in Rome.
AB  - The present paper reports a socio-acoustic survey carried out in three large
      urban parks in Rome, selected on the basis of the outcome of a preliminary online
      survey. According to the experimental protocol applied in a previous study
      carried out in Milan and Naples, binaural recordings in 85 sites and interviews
      with 266 users of the three parks were performed only during the day in
      summertime. On the basis of selected acoustical descriptors, the sonic
      environment of the three parks was categorized and, thanks to statistical
      analysis, three clusters were identified. The results confirm that the sound
      environment in urban parks is often considered as "good" or "excellent" even if
      the sound pressure level is nearly always higher than the limits commonly used to
      define quiet areas. This is due to the influence of other factors, such as the
      presence of trees, natural features, and the tranquility; all of these components
      cannot be neglected in the assessment of the soundscape because they directly
      affect the psychological state of the person. 

PMID- 23862890
TI  - Psychoacoustical evaluation of natural and urban sounds in soundscapes.
AB  - Among various sounds in the environment, natural sounds, such as water sounds and
      birdsongs, have proven to be highly preferred by humans, but the reasons for
      these preferences have not been thoroughly researched. This paper explores
      differences between various natural and urban environmental sounds from the
      viewpoint of objective measures, especially psychoacoustical parameters. The
      sound samples used in this study include the recordings of single sound source
      categories of water, wind, birdsongs, and urban sounds including street music,
      mechanical sounds, and traffic noise. The samples are analyzed with a number of
      existing psychoacoustical parameter algorithmic models. Based on hierarchical
      cluster and principal components analyses of the calculated results, a series of
      differences has been shown among different sound types in terms of key
      psychoacoustical parameters. While different sound categories cannot be
      identified using any single acoustical and psychoacoustical parameter,
      identification can be made with a group of parameters, as analyzed with
      artificial neural networks and discriminant functions in this paper. For
      artificial neural networks, correlations between network predictions and targets
      using the average and standard deviation data of psychoacoustical parameters as
      inputs are above 0.95 for the three natural sound categories and above 0.90 for
      the urban sound category. For sound identification/classification, key parameters
      are fluctuation strength, loudness, and sharpness. 

PMID- 23862891
TI  - A computational model of auditory attention for use in soundscape research.
AB  - Urban soundscape design involves creating outdoor spaces that are pleasing to the
      ear. One way to achieve this goal is to add or accentuate sounds that are
      considered to be desired by most users of the space, such that the desired sounds
      mask undesired sounds, or at least distract attention away from undesired sounds.
      In view of removing the need for a listening panel to assess the effectiveness of
      such soundscape measures, the interest for new models and techniques is growing.
      In this paper, a model of auditory attention to environmental sound is presented,
      which balances computational complexity and biological plausibility. Once the
      model is trained for a particular location, it classifies the sounds that are
      present in the soundscape and simulates how a typical listener would switch
      attention over time between different sounds. The model provides an acoustic
      summary, giving the soundscape designer a quick overview of the typical sounds at
      a particular location, and allows assessment of the perceptual effect of
      introducing additional sounds. 

PMID- 23862892
TI  - Computationally robust and noise resistant numerical detector for the detection
      of atmospheric infrasound.
AB  - This work reports on a performance study of two numerical detectors that are
      particularly useful for infrasound arrays operating under windy conditions. The
      sum of squares of variance ratios (SSVR1)-proposed for detecting signals with
      frequency ranging from 1 to 10 Hz-is computed by taking the ratio of the squared
      sum of eigenvalues to the square of largest eigenvalue of the covariance matrix
      of the power spectrum. For signals with lower frequency between 0.015 and 0.1 Hz,
      SSVR2 is developed to reduce the detector's sensitivity to noise. The detectors'
      performances are graphically compared against the current method, the mean of
      cross correlation maxima (MCCM), using the receiver operating characteristics
      curves and three types of atmospheric infrasound, corrupted by Gaussian and Pink
      noise. The MCCM and SSVR2 detectors were also used to detect microbaroms from the
      24 h-long infrasound data. It was found that the two detectors outperform the
      MCCM detector in both sensitivity and computational efficiency. For mine blasts
      corrupted by Pink noise (signal-to-noise ratio = -7 dB), the MCCM and SSVR1
      detectors yield 62 and 88 % true positives when accepting 20% false positives.
      For an eight-sensor array, the speed gain is approximately eleven-fold for a 50 s
      long signal. 

PMID- 23862893
TI  - Assessment of urban soundscapes with the focus on an architectural installation
      with musical features.
AB  - Urban soundscapes at five locations in the city of Zadar were perceptually
      assessed by on-site surveys and objectively evaluated based on monaural and
      binaural recordings. All locations were chosen so that they would display
      auditory and visual diversity as much as possible. The unique sound installation
      known as the Sea Organ was included as an atypical music-like environment.
      Typical objective parameters were calculated from the recordings related to the
      amount of acoustic energy, spectral properties of sound, the amount of
      fluctuations, and tonal properties. The subjective assessment was done on-site
      using a common survey for evaluating the properties of sound and visual
      environment. The results revealed the importance of introducing the context into
      soundscape research because objective parameters did not show significant
      correlation with responses obtained from interviewees. Excessive values of
      certain objective parameters could indicate that a sound environment will be
      perceived as unpleasant or annoying, but its overall perception depends on how
      well it agrees with people's expectations. This was clearly seen for the case of
      Sea Organ for which the highest values of objective parameters were obtained,
      but, at the same time, it was evaluated as the most positive sound environment in
      every aspect. 

PMID- 23862894
TI  - Narrow-band autocorrelation function features for the automatic recognition of
      acoustic environments.
AB  - Acoustic environments are typically composed of multiple sound sources of
      different typologies, making them especially complex to model and parameterize.
      To develop an automatic acoustic environment recognition system, this work
      proposes a spectro-temporal signal parameterization technique inspired by human
      perception. The proposed parameters are derived from the analysis of the
      autocorrelation function of narrow-band signals (NB-ACF) obtained from an
      auditory gammatone filter bank. Five features related to acoustic phenomena are
      extracted from the NB-ACF to parameterize sound signals. Experiments are
      conducted on a 4 h sound database (composed of 15 different acoustic
      environments) employing four different machine learning techniques: K-nearest
      neighbor, Gaussian mixture models, neural networks and support vector machines.
      The averaged recognition rates increase by 4.5% when using the proposed NB-ACF
      features instead of the popular Mel frequency cepstral coefficients. The
      improvement is even greater (5.6%) when the features are tested in acoustic
      environments from unknown locations. These results are attributed to the better
      modeling of the acoustic environments thanks to the complementarity of the
      spectro-temporal features derived from NB-ACF analysis. 

PMID- 23862895
TI  - Application of a recently introduced index for acoustic complexity to an avian
      soundscape with traffic noise.
AB  - An altered acoustic environment can have severe consequences for natural
      communities, especially for species that use acoustic signals to communicate and
      achieve breeding success. Numerous studies have focused on traffic noise
      disturbance, but the possible causes of road effects are inter-correlated and the
      literature on noise qua noise is sometimes contradictory. To provide further
      empirical data in this regard, the authors investigated the spatio-temporal
      variability of the singing dynamics of an avian community living in an acoustic
      context altered by traffic noise. Fieldwork was carried out in a wood of Turkey
      oaks (central Italy) bordered on one side by a main road. The soundscape was
      examined by positioning eight digital recorders, distributed in two transects
      perpendicular to the road, and recording between 6:30 and 8.30 a.m. for 12
      continuous sessions. The acoustic complexity index was used to obtain a
      quantification of singing dynamics, which were positively correlated with traffic
      noise. This may indicate that birds try to propagate their signals with greater
      emphasis (e.g., amplified redundancy or loudness of the songs) to override the
      masking effect of noise. Nevertheless, an ecotonal effect could have influenced
      the correlation results, with this enhanced dynamic possibly being due to a more
      densely populated environment. 

PMID- 23862896
TI  - Beam forming of the underwater sound field from impact pile driving.
AB  - Observations of underwater noise from impact pile driving were made with a
      vertical line array. Previous studies [Reinhall and Dahl, J. Acoust. Soc. Am.
      130, 1209-1216 (2011)] show that the dominant underwater noise from impact
      driving is from the Mach wave associated with the radial expansion of the pile
      that propagates down the pile at supersonic speed after impact. Here precise
      estimates of the vertical arrival angles associated with the down- and up-going
      Mach wave are made via beam forming, and the energy budget of the arrival
      structure is quantified. 

PMID- 23862897
TI  - Using local binary patterns as features for classification of dolphin calls.
AB  - An image processing technique called Local Binary Patterns (LBP) has been
      explored for its ability to generate feature vectors for dolphin vocalization
      classification. The LBP operator eliminates the need for contour tracing,
      denoising, and other prior processing. In an experimental study of classifying
      dolphin whistle types, the performance of the LBP operation was compared with
      that of the popular contour-based Time-Frequency Parameters (TFP) approach. The
      preliminary experimental results illustrate that the LBP method produces more
      consistent classifier accuracy of dolphin whistle calls even when the contour
      shapes are complex and populated with impulsive clicks and anthropogenic
      harmonics. 

PMID- 23862898
TI  - Acoustic contrast sensitivity to transfer function errors in the design of a
      personal audio system.
AB  - An analytic means to evaluate the error sensitivity of a personal audio system is
      proposed. The personal audio system, which focuses acoustic energy into a zone of
      interest using multiple loudspeakers, is subject to various errors when
      implemented. The performance of a personal audio system, defined as an energy
      ratio between the zone of interest and the rest, is inevitably influenced by
      errors. Thus the ability to predict performance change at the design stage is
      crucial when building a robust personal audio system. The dependence of the
      energy ratio change on various types of errors is formulated. 

PMID- 23862899
TI  - Maintaining intelligibility at high speech intensities: evidence of lateral
      inhibition in the lower auditory pathway.
AB  - Three experiments examined the intelligibility enhancement produced when noise
      bands flank high intensity narrowband speech. Enhancement was unaffected by noise
      gating (experiment 1), ruling out peripheral adaptation as a source, and was also
      unaffected by interaural decorrelation of noise bands flanking diotic speech
      (experiment 2), indicating that enhancement occurs prior to binaural processing.
      These results support previous suggestions that intelligibility loss at high
      intensities is reduced by lateral inhibition in the cochlear nuclei. Results from
      a final experiment suggest that this effect is only ipsilateral, implicating a
      specific population of inhibitory neurons. 

PMID- 23862900
TI  - Frequency-change aftereffect produced by adaptation to real and illusory
      unidirectional frequency sweeps.
AB  - It was examined whether illusory and real continuities induce the frequency
      change aftereffect, in which repeated exposure to a frequency sweep results in a
      shift in the perceived frequency change direction of a subsequent test sound. The
      magnitude of the aftereffect for different types of adaptors ("real sweep,"
      "illusory sweep," and "sweep with gap") was compared. Listeners judged the
      direction of a frequency change of the test sound and showed a significant
      aftereffect only for the "real sweep" adaptors. The results suggest that the
      illusory sweeps are processed after the stage of frequency-change detection. 

PMID- 23862901
TI  - Prosodic boundary information modulates phonetic categorization.
AB  - Categorical perception experiments were performed on an English /b-p/ voice onset
      time (VOT) continuum with native (American English) and non-native (Korean)
      listeners to examine whether and how phonetic categorization is modulated by
      prosodic boundary and language experience. Results demonstrated perceptual
      shifting according to prosodic boundary strength: A longer VOT was required to
      identify a sound as /p/ after an intonational phrase than a word boundary,
      regardless of the listeners' language experience. This suggests that segmental
      perception is modulated by the listeners' computation of an abstract prosodic
      structure reflected in phonetic cues of phrase-final lengthening and domain
      initial strengthening, which are common across languages. 

PMID- 23862902
TI  - A phonetic explanation of pronunciation variant effects.
AB  - Effects of word-level phonetic variation on the recognition of words with
      different pronunciation variants (e.g., center produced with/(out) [t]) are
      investigated via the semantic- and pseudoword-priming paradigms. A bias favoring
      clearly articulated words with canonical variants ([nt]) is found. By reducing
      the bias, words with different variants show robust and equivalent lexical
      activation. The equivalence of different word forms highlights a snag for
      frequency-based theories of lexical access: How are words and word productions
      with vastly different frequencies recognized equally well by listeners? A process
      based account is proposed, suggesting that careful speech induces bottom-up
      processing and casual speech induces top-down processing. 

PMID- 23862903
TI  - Acoustic method for calibration of audiometric bone vibrators. II. Harmonic
      distortion.
AB  - A previous report [Margolis and Stiepan (2012). "Acoustic method for calibration
      of audiometric bone vibrators," J. Acoust. Soc. Am. 131, 1221-1225] described a
      reliable, inexpensive, acoustic method for calibration of audiometric bone
      vibrators. As a follow up to that report harmonic distortion measurements were
      made with the standard electromechanical method and the acoustic method using
      five Radioear B71 vibrators and one Radioear B81 prototype vibrator. Lower
      distortion was seen for measurements made with the acoustic method compared to
      the electromechanical method and for the Radioear B81 vibrator compared to the
      Radioear B71 vibrator. 

PMID- 23862904
TI  - Experimental measurement of the acoustic sensitivity kernel.
AB  - In the Born approximation, the acoustic scattering from a spherical obstacle of a
      size comparable to the acoustic wavelength can be evaluated in the framework of
      the sensitivity kernel approach, which describes the relationship between the
      pressure-field fluctuation and the position of a local change in the propagation
      medium. The spatial structure of the sensitivity kernel is here investigated
      through experimental observations made in a water tank at the ultrasonic scale
      and compared to an analytical model. The pattern of the sensitivity kernel is
      discussed in the case of a source-to-receiver wave field that includes a direct
      path and one surface reflection. 

PMID- 23862905
TI  - Disambiguating durational cues for speech segmentation.
AB  - Vowels are lengthened in lexically stressed syllables and also in word-final
      syllables. Both stress and final-syllable lengthening can assist in word
      segmentation from continuous speech, but in languages like English, with a
      preponderance of stress-initial words, lengthening cues may conflict for
      indicating word boundaries. An analysis of a large corpus of English speech
      demonstrated that speakers provide distributional information sufficient to
      potentially allow listeners to determine whether vowel lengthening is associated
      with lexical stress or word finality without relying on a congruence of multiple
      suprasegmental cues to make the distinction. 

PMID- 23862906
TI  - A high amplitude, time reversal acoustic non-contact excitation (trance).
AB  - This paper describes the principle behind a high amplitude non-contact acoustic
      source based on the principle of time reversal (TR), a process to focus energy at
      a point in space. By doing the TR in an air filled, hollow cavity and using a
      laser vibrometer in the calibration of the system, a non-contact source may be
      created. This source is proven to be more energetic than an off the shelf focused
      ultrasound transducer. A scaled up version of the proposed source has the
      potential to allow nondestructive evaluation processes that require high
      amplitude, such as nonlinear elastic wave spectroscopy (NEWS) techniques. 

PMID- 23862907
TI  - Experimental evaluation of flow-induced noise in level flight of the pigeon
      (Columba livia).
AB  - The experimental method employed in an anechoic wind tunnel to characterize flow
      induced noise of the pigeon (Columba livia) during level flight is described in
      this letter. A live pigeon was managed to maintain a steady level flight at the
      wind tunnel test flow of 15 m/s. A microphone array was fabricated, and the
      conventional beamforming method was then adopted to yield the corresponding
      narrowband acoustic images and broadband sound pressure spectral results. The
      results justified the experimental method developed in this work. It can be seen
      that the flight noise of the pigeon is mostly from the wing tips. In addition,
      the spectral waveform of the pigeon flight suggests a slope of -20 dB/dec between
      500 Hz and 5 kHz. 

PMID- 23862908
TI  - Extraction of otoacoustic distortion product sources using pulse basis functions.
AB  - Distortion product otoacoustic emissions (DPOAEs) acquired in normal-hearing
      subjects show considerable variation in amplitude with varying frequency. This is
      known as DPOAE fine structure. It is widely accepted that fine structure results
      from wave interference from two DPOAE sources, a non-linear generation component
      and a coherent reflection component. Here a method is presented that decomposes
      short-pulse DPOAE recordings into pulse basis functions and enables the
      quantification of both source components in the time domain, independent of their
      relative phase and at low cost of measurement time. Input-output functions
      utilizing the extracted primary-source component are analyzed. 

PMID- 23862909
TI  - Three-dimensional mapping of evolving internal waves during the Shallow Water
      2006 experiment.
AB  - Detailed knowledge of sound speed profiles and the sound speed profile's spatial
      and temporal variability resulting from internal waves (IWs) are indispensable to
      investigating significant acoustic field fluctuations in shallow water. A
      strategy to obtain a time-varying, three-dimensional (3D) IW temperature field is
      presented. It uses two types of simultaneous measurements: dense observations
      from a farm of thermistor strings and IW surface expressions from a ship-based
      radar. Using data from the Shallow Water 2006 experiment, the temperature field,
      over multiple kilometers in range, was reconstructed and, fed to a 3D acoustic
      model to demonstrate IW impacts on acoustic propagation. 

PMID- 23862910
TI  - Enhanced voice activity detection in kernel subspace domain.
AB  - This paper proposes a voice activity detection (VAD) method in a kernel subspace
      domain to improve the performance of the kernel-based VAD. A linear transform
      matrix that can simultaneously diagonalize the two covariance matrices using
      kernel principal component analysis is presented to generate the kernel subspace.
      The likelihood ratio test based on Gaussian distributions is applied for the VAD
      in the kernel subspace. Experimental results show that the proposed VAD algorithm
      outperforms the conventional approaches under various noise conditions. 

PMID- 23862911
TI  - Localization of a noisy broadband surface target using time differences of
      multipath arrivals.
AB  - Previous studies [Tiemann et al., J. Acoust. Soc. Am. 120, 2355-2365 (2006)] have
      reported the localization of marine mammals in 3-D from their clicks using
      multipath arrivals. Bathymetric variations were advantageously used to predict
      multipath arrival times with a raytracer. These arrivals are directly discernible
      from the time series for impulsive sources, such as whale clicks, but extension
      of the method to continuous broadband sources presents additional complications.
      By pulse compressing noise emitted from a small boat using two hydrophones, the
      hyperbolic direct-arrival ambiguity can be refined in both range and bearing.
      Acoustic-derived results are validated with target GPS measurements. 

PMID- 23862912
TI  - Development of a matched filter detector for acoustic signals at local distances
      from small explosions.
AB  - A method for acoustic detection of small explosions at local distances is
      presented combining a matched filter with a p-value representing the conditional
      probability of detection. Because the physics of signal generation and
      propagation for small, locally recorded acoustic signals from small explosions is
      well understood, the single hypothesis to be tested is a signal corrupted by
      additive noise. A simple analytical signal representation is used where a known
      signal is assumed with parameters to be determined. The advantage of the approach
      is that the detector can be combined with other detectors that measure different
      signal characteristics all under the same unifying hypothesis. 

PMID- 23862913
TI  - The roles of fundamental frequency contours and sentence context in Mandarin
      Chinese speech intelligibility.
AB  - Flattening the fundamental frequency (F0) contours of Mandarin Chinese sentences
      reduces their intelligibility in noise but not in quiet. It is unclear, however,
      how the absence of primary acoustic cue for lexical tones might be compensated
      with the top-down information of sentence context. In this study, speech
      intelligibility was evaluated when participants listened to sentences and word
      lists with or without F0 variations in quiet and noise. The results showed that
      sentence context partially explained the unchanged intelligibility of monotonous
      Chinese sentences in quiet and further indicate that F0 variations and sentence
      context act in concert during speech comprehension. 

PMID- 23862914
TI  - Temporal predictability as a grouping cue in the perception of auditory streams.
AB  - This study reports a role of temporal regularity on the perception of auditory
      streams. Listeners were presented with two-tone sequences in an A-B-A-B rhythm
      that was either regular or had a controlled amount of temporal jitter added
      independently to each of the B tones. Subjects were asked to report whether they
      perceived one or two streams. The percentage of trials in which two streams were
      reported substantially and significantly increased with increasing amounts of
      temporal jitter. This suggests that temporal predictability may serve as a
      binding cue during auditory scene analysis. 

PMID- 23862915
TI  - Communication: Selection rules for tunneling splitting of vibrationally excited
      levels.
AB  - Five symmetry-based selection rules are formulated that relate the tunneling
      splitting of a vibrationally excited level to that of the ground level in
      molecules with a symmetric double-minimum potential. The rules, which explain why
      excited levels frequently have smaller splittings than zero-point levels, are
      used to interpret the observed and calculated splittings in malonaldehyde. 

PMID- 23862916
TI  - Communication: The distinguishable cluster approximation.
AB  - We present a method that accurately describes strongly correlated states and
      captures dynamical correlation. It is derived as a modification of coupled
      cluster theory with single and double excitations (CCSD) through consideration of
      particle distinguishability between dissociated fragments, whilst retaining the
      key desirable properties of particle-hole symmetry, size extensivity, invariance
      to rotations within the occupied and virtual spaces, and exactness for two
      electron subsystems. The resulting method, called the distinguishable cluster
      approximation, smoothly dissociates difficult cases such as the nitrogen
      molecule, with the modest N(6) computational cost of CCSD. Even for molecules
      near their equilibrium geometries, the new model outperforms CCSD. It also
      accurately describes the massively correlated states encountered when
      dissociating hydrogen lattices, a proxy for the metal-insulator transition, and
      the fully dissociated system is treated exactly. 

PMID- 23862917
TI  - Communication: Spectral representation of the Lamb shift for atomic and molecular
      calculations.
AB  - A spectral representation of the self-energy based on hydrogenic atomic data is
      examined for its usefulness to evaluate the self-energy of many-electron atoms,
      and thus its potential for molecular calculations. Use of the limited hydrogenic
      data with a diagonal projection overestimates the valence self-energy by an order
      of magnitude. The same diagonal projection for the vacuum polarization produces a
      similar overestimate, but a full projection produces values that are within a
      factor of 2 of the exact value, as does a density-fitting procedure. 

PMID- 23862918
TI  - Communication: Two-determinant mixing with a strong-correlation density
      functional.
AB  - In recent papers [A. D. Becke, J. Chem. Phys. 138, 074109 (2013); ibid. 138,
      161101 (2013)], a density functional for strong correlations in quantum chemistry
      was introduced. The functional is designed to capture molecular dissociation
      limits using symmetry-restricted orbitals. Here we demonstrate that the
      functional describes, with good accuracy, two-determinant multi-reference states.
      The examples of this work involve 50/50 mixing of symmetry-equivalent Slater
      determinants at avoided crossings. We employ exactly-computed exchange and
      fractional spin-orbital occupancies. The connection with dissociated systems and
      single-determinant reference states is explained. 

PMID- 23862919
TI  - Communication: Spin-free quantum computational simulations and symmetry adapted
      states.
AB  - The ideas of digital simulation of quantum systems using a quantum computer
      parallel the original ideas of numerical simulation using a classical computer.
      In order for quantum computational simulations to advance to a competitive point,
      many techniques from classical simulations must be imported into the quantum
      domain. In this article, we consider the applications of symmetry in the context
      of quantum simulation. Building upon well established machinery, we propose a
      form of first quantized simulation that only requires the spatial part of the
      wave function, thereby allowing spin-free quantum computational simulations. We
      go further and discuss the preparation of N-body states with specified symmetries
      based on projection techniques. We consider two simple examples, molecular
      hydrogen and cyclopropenyl cation, to illustrate the ideas. The methods here are
      the first to explicitly deal with preparing N-body symmetry-adapted states and
      open the door for future investigations into group theory, chemistry, and quantum
      simulation. 

PMID- 23862920
TI  - Communication: Vibrational spectroscopy of Au4 from high resolution photoelectron
      imaging.
AB  - High resolution photoelectron spectroscopy of Au4 (-) is reported using a new
      photoelectron imaging apparatus. A broad vibrational progression is resolved for
      the detachment transition from the ground electronic state of the Y-shaped Au4 (
      ) to that of the Y-shaped Au4 neutral (C2v, (1)A1) in the nu2 vibrational mode
      with a harmonic frequency of 171(7) cm(-1) and an anharmonicity of ~0.5 cm(-1).
      In addition, two low frequency modes with weak Franck-Condon factors are
      observed: the v3 mode with a frequency of 97(7) cm(-1) and the v6 mode with a
      frequency of 17(7) cm(-1). An accurate electron affinity of 2.7098(6) eV is
      obtained for the Y-shaped Au4 neutral cluster. The current study shows that very
      low frequency vibrational modes can be resolved for size-selected clusters using
      high resolution photoelectron imaging, providing valuable additional experimental
      information for cluster structure determination. 

PMID- 23862921
TI  - Communication: Fourier-transform infrared probing of remarkable quantities of gas
      trapped in cold homogeneously nucleated nanodroplets.
AB  - Studies of catalyzed all-vapor gas-hydrate formation on a sub-second timescale
      have been extended with a special focus on liquid-droplet compositions at the
      instant of hydrate crystallization. This focus has been enabled by inclusion of
      methanol in the all-vapor mixture. This slows droplet to gas-hydrate conversion
      near 200 K to a time scale suited for standard FTIR sampling. Such droplet data
      are sought as a guide to ongoing efforts to reduce the amount of guest catalyst
      required for instant formation of the gas hydrates. For the same reason, all
      vapor sampling has also been extended to the generation of long-lived liquid
      droplets with reduced or no water content. Observations of single-solvent
      droplets show that surprising quantities of gas molecules are trapped during
      rapid droplet growth. For example, CO2 is trapped at levels near 50 mol. % in
      droplets of acetone, tetrahydrofuran, or trimethylene oxide formed under CO2
      pressures of several Torr in a cold-chamber at 170 K. Less but significant
      amounts of gas are trapped at higher temperatures, or in methanol or water
      methanol droplets. The droplet metastability appears to commonly lead to
      formation of bubbles larger than the original nanodroplets. Besides serving as a
      guide for the all-vapor gas-hydrate studies, the semiquantitative evidence of
      extensive trapping of gases is expected to have a role in future studies of
      atmospheric aerosols. 

PMID- 23862922
TI  - Communication: Active-space decomposition for molecular dimers.
AB  - We have developed an active-space decomposition strategy for molecular dimers
      that allows for the efficient computation of the dimer's complete-active-space
      wavefunction while only constructing the monomers' active-space wavefunctions.
      Dimer states are formed from linear combinations of direct products of localized
      orthogonal monomer states and Hamiltonian matrix elements are computed directly
      without explicitly constructing the product space. This decomposition is
      potentially exact in the limit where a full set of monomer states is included.
      The adiabatic states are then found by diagonalizing the dimer Hamiltonian
      matrix. We demonstrate the convergence of our method to a complete-active-space
      calculation of the full dimer with two test cases: the benzene and naphthalene
      dimers. 

PMID- 23862923
TI  - The application of the thermodynamic perturbation theory to study the hydrophobic
      hydration.
AB  - The thermodynamic perturbation theory was tested against newly obtained Monte
      Carlo computer simulations to describe the major features of the hydrophobic
      effect in a simple 3D-Mercedes-Benz water model: the temperature and hydrophobe
      size dependence on entropy, enthalpy, and free energy of transfer of a simple
      hydrophobic solute into water. An excellent agreement was obtained between the
      theoretical and simulation results. Further, the thermodynamic perturbation
      theory qualitatively correctly (with respect to the experimental data) describes
      the solvation thermodynamics under conditions where the simulation results are
      difficult to obtain with good enough accuracy, e.g., at high pressures. 

PMID- 23862924
TI  - Double asymptotic expansion of three-center electronic repulsion integrals.
AB  - A double asymptotic expansion for the evaluation of three-center electron
      repulsion integrals (ERIs) in the long-range limit is presented. For the
      definition of this limit, a natural division of space based on the atomic
      coordinates and basis function exponents in utilized. The resulting analytical
      expression for the calculation of three-center ERIs in the long-range limit are
      implemented in the density functional theory program deMon2k. Validation and
      benchmark calculations of n-alkanes, hydrogen saturated graphene sheets and
      hydrogen saturated diamond blocks are discussed. It is shown that for a
      sufficient large number of long-range ERIs, the linear scaling regime is reached.

PMID- 23862925
TI  - Accurate basis set truncation for wavefunction embedding.
AB  - Density functional theory (DFT) provides a formally exact framework for
      performing embedded subsystem electronic structure calculations, including DFT-in
      DFT and wavefunction theory-in-DFT descriptions. In the interest of efficiency,
      it is desirable to truncate the atomic orbital basis set in which the subsystem
      calculation is performed, thus avoiding high-order scaling with respect to the
      size of the MO virtual space. In this study, we extend a recently introduced
      projection-based embedding method [F. R. Manby, M. Stella, J. D. Goodpaster, and
      T. F. Miller III, J. Chem. Theory Comput. 8, 2564 (2012)] to allow for the
      systematic and accurate truncation of the embedded subsystem basis set. The
      approach is applied to both covalently and non-covalently bound test cases,
      including water clusters and polypeptide chains, and it is demonstrated that
      errors associated with basis set truncation are controllable to well within
      chemical accuracy. Furthermore, we show that this approach allows for switching
      between accurate projection-based embedding and DFT embedding with approximate
      kinetic energy (KE) functionals; in this sense, the approach provides a means of
      systematically improving upon the use of approximate KE functionals in DFT
      embedding. 

PMID- 23862926
TI  - On asymptotic behavior of density functional theory.
AB  - The performance of several previously proposed as well as of some novel
      approaches for correcting the asymptotic behavior of electron densities in
      density functional theory (DFT) is evaluated. The comparisons are made for
      molecular properties that are known to be sensitive to the asymptotic behavior of
      densities such as polarizabilities, energies of excitations to Rydberg states,
      and interaction energies (computed using symmetry-adapted perturbation theory).
      We find that whereas DFT-based methods without asymptotic corrections predict the
      investigated properties with errors often as large as a dozen or so percent
      relative to the best known values, the best performing asymptotically corrected
      hybrid functionals reduce these errors to below 2%. In many cases, the errors are
      just a fraction of one percent and in a few cases DFT reproduces benchmark values
      to all figures. These errors are also very close to those produced by the coupled
      cluster methods at the highest levels of electron excitations applicable in
      practice. Such performance is unprecedented for any applications of DFT and is
      due to high sensitivity of the investigated properties to tails of the electron
      densities. Range-separated hybrid (RSH) functionals are also examined and found
      to perform comparably to the asymptotically corrected hybrid functionals for
      excitation energies and only somewhat worse for polarizabilities. However, very
      surprisingly, RSH functionals fail completely in interaction energy calculations.
      We explain the latter problem by showing that, despite some expectations in the
      literature reflected by the alternative name, long-range corrected, used for the
      RSH functionals, these methods give densities that are not better in the
      asymptotic region than those produced by asymptotically uncorrected standard DFT
      methods. We further show that this failure can be corrected by cutting,
      displacing, and splicing the exchange-correlation potentials of RSH methods such
      that these potentials approach the correct value at infinity. 

PMID- 23862927
TI  - Modeling opto-electronic properties of a dye molecule in proximity of a
      semiconductor nanoparticle.
AB  - A general methodology is presented to model the opto-electronic properties of a
      dye molecule in the presence of a semiconductor nanoparticle (NP), a model system
      for the architecture of dye-sensitized solar cells. The method is applied to the
      L0 organic dye solvated with acetonitrile in the neighborhood of a TiO2 NP. The
      total reaction potential due to the polarization of the solvent and the metal
      oxide is calculated by extending the polarizable continuum model integral
      equation formalism. The ground state energy is computed by using density
      functional theory (DFT) while the vertical electronic excitations are obtained by
      time-dependent DFT in a state-specific corrected linear response scheme. We
      calculate the excited state oxidation potential (ESOP) for the protonated and
      deprotonated forms of the L0 dye at different distances and configurations with
      respect to the NP surface. The stronger renormalizations of the ESOP values due
      to the presence of the TiO2 nanostructure are found for the protonated dye,
      reaching a maximum of about -0.15 eV. The role of protonation effect is discussed
      in terms of the atomic Lowdin charges of the oxidized and reduced species. On the
      other hand, we observed a weak effect on the L0 optical excitation gap due to the
      polarization response of the NP. 

PMID- 23862928
TI  - Controlling the efficiency of trapping in treelike fractals.
AB  - Efficiently controlling the trapping process, especially the trapping efficiency,
      is central in the study of trap problem in complex systems, since it is a
      fundamental mechanism for diverse other dynamic processes. Thus, it is of
      theoretical and practical significance to study the control technique for
      trapping problem. In this paper, we study the trapping problem in a family of
      proposed directed fractals with a deep trap at a central node. The directed
      fractals are a generalization of previous undirected fractals by introducing the
      directed edge weights dominated by a parameter. We characterize all the
      eigenvalues and their degeneracies for an associated matrix governing the
      trapping process. The eigenvalues are provided through an exact recursive
      relation deduced from the self-similar structure of the fractals. We also obtain
      the expressions for the smallest eigenvalue and the mean first-passage time
      (MFPT) as a measure of trapping efficiency, which is the expected time for the
      walker to first visit the trap. The MFPT is evaluated according to the proved
      fact that it is approximately equal to reciprocal of the smallest eigenvalue. We
      show that the MFPT is controlled by the weight parameter by modifying which the
      MFPT can scale superlinealy, linearly, or sublinearly with the system size. Thus,
      this work paves a way to delicately controlling the trapping process in the
      fractals. 

PMID- 23862929
TI  - Using the uncertainty principle to design simple interactions for targeted self
      assembly.
AB  - We present a method that systematically simplifies isotropic interactions
      designed for targeted self-assembly. The uncertainty principle is used to show
      that an optimal simplification is achieved by a combination of heat kernel
      smoothing and Gaussian screening of the interaction potential in real and
      reciprocal space. We use this method to analytically design isotropic
      interactions for self-assembly of complex lattices and of materials with
      functional properties. The derived interactions are simple enough to narrow the
      gap between theory and experimental implementation of theory based designed self
      assembling materials. 

PMID- 23862930
TI  - Predicting phase behavior in multicomponent mixtures.
AB  - Mixtures with a large number of components can undergo phase transitions of a
      hybrid character, with both condensation and demixing contributions. We describe
      a robust Monte Carlo simulation method for calculating phase coexistence in
      multicomponent mixtures. We use this approach to study the phase behavior of
      lattice models of multicomponent mixtures with strongly varying pair
      interactions. Such a system can be thought of as a simplified model of the
      cytosol, with both specific and nonspecific interactions. We show that mapping a
      multicomponent mixture onto an approximately equivalent one-component system
      yields both upper and lower bounds on the maximum solute volume fraction of a
      stable, homogeneous phase. By following the minimum excess-free-energy path from
      the dilute phase free-energy minimum, we predict the difference in composition
      between the condensed and dilute phases at the boundary of the homogeneous phase.
      We find that this "direction" of phase separation rarely aligns with the dominant
      direction of density fluctuations in the dilute phase. We also show that demixing
      transitions tend to lower the maximum solute volume fraction at which the
      homogeneous phase is stable. By considering statistical ensembles of mixtures
      with random interactions, we show that the demixing contribution to phase
      separation is self-averaging and dependent only on the mean and variance of the
      distribution of interactions. 

PMID- 23862931
TI  - Quantum dephasing of a two-state system by a nonequilibrium harmonic oscillator.
AB  - In this paper, we investigate coherent quantum dynamics in a nonequilibrium
      environment. We focus on a two-state quantum system strongly coupled to a single
      classical environmental oscillator, and explore the effect of nonstationary
      statistical properties of the oscillator on the quantum evolution. A simple
      nonequilibrium model, consisting of an oscillator with a well-defined initial
      phase which undergoes subsequent diffusion, is introduced and studied.
      Approximate but accurate analytic expressions for the evolution of the off
      diagonal density matrix element of the quantum system are derived in the second
      order cumulant approximation. The effect of the initial phase choice on the
      subsequent quantum evolution is quantified. It is observed that the initial phase
      can have a significant effect on the preservation of coherence on short time
      scales, suggesting this variable as a control parameter for optimizing coherence
      in many-body quantum systems. 

PMID- 23862932
TI  - Orbital optimized double-hybrid density functionals.
AB  - This paper advocates development of a new class of double-hybrid (DH) density
      functionals where the energy is fully orbital optimized (OO) in presence of all
      correlation, rather than using a final non-iterative second order perturbative
      correction. The resulting OO-DH functionals resolve a number of artifacts
      associated with conventional DH functionals, such as first derivative
      discontinuities. To illustrate the possibilities, two non-empirical OO-DH
      functionals are obtained from existing DH functionals based on PBE: OO-PBE0-DH
      and OO-PBE0-2. Both functionals share the same functional form, with parameters
      determined on the basis of different physical considerations. The new functionals
      are tested on a variety of bonded, non-bonded and symmetry-breaking problems. 

PMID- 23862934
TI  - Infrared absorption imaging of 2D supersonic jet expansions: Free expansion,
      cluster formation, and shock wave patterns.
AB  - N2O/He gas mixtures are expanded through a 10 * 0.5 mm(2) slit nozzle and imaged
      by direct absorption vibrational spectroscopy, employing a HgCdTe focal plane
      array detector after interferometric modulation. N2O cluster formation in the
      free supersonic expansion is visualized. The expansion structure behind the
      frontal shock is investigated as a function of background pressure. At high
      pressures, a sequence of stationary density peaks along a narrow directed flow
      channel is characterized. The potential of the technique for the elucidation of
      aggregation mechanisms is emphasized. 

PMID- 23862935
TI  - Ultra-precise particle velocities in pulsed supersonic beams.
AB  - We describe an improved experimental method for the generation of cold, directed
      particle bunches, and the highly accurate determination of their velocities in a
      pulsed supersonic beam, allowing for high-resolution experiments of atoms,
      molecules, and clusters. It is characterized by a pulsed high pressure jet source
      with high brilliance and optimum repeatability, a flight distance of few metres
      that can be varied with a tolerance of setting of 50 MUm, and a precision in the
      mean flight time of particles of better than 10(-4). The technique achieves
      unmatched accuracies in particle velocities and kinetic energies and also permits
      the reliable determination of enthalpy changes with very high precision. 

PMID- 23862933
TI  - Phase-field approach to implicit solvation of biomolecules with Coulomb-field
      approximation.
AB  - A phase-field variational implicit-solvent approach is developed for the
      solvation of charged molecules. The starting point of such an approach is the
      representation of a solute-solvent interface by a phase field that takes one
      value in the solute region and another in the solvent region, with a smooth
      transition from one to the other on a small transition layer. The minimization of
      an effective free-energy functional of all possible phase fields determines the
      equilibrium conformations and free energies of an underlying molecular system.
      All the surface energy, the solute-solvent van der Waals interaction, and the
      electrostatic interaction are coupled together self-consistently through a phase
      field. The surface energy results from the minimization of a double-well
      potential and the gradient of a field. The electrostatic interaction is described
      by the Coulomb-field approximation. Accurate and efficient methods are designed
      and implemented to numerically relax an underlying charged molecular system.
      Applications to single ions, a two-plate system, and a two-domain protein reveal
      that the new theory and methods can capture capillary evaporation in hydrophobic
      confinement and corresponding multiple equilibrium states as found in molecular
      dynamics simulations. Comparisons of the phase-field and the original sharp
      interface variational approaches are discussed. 

PMID- 23862936
TI  - The translational, rotational, and vibrational energy effects on the chemical
      reactivity of water cation H2O+(X 2B1) in the collision with deuterium molecule
      D2.
AB  - By employing the newly established vacuum ultraviolet (VUV) laser pulsed field
      ionization-photoion (PFI-PI) double quadrupole-double octopole ion guide
      apparatus, we have examined the translational, rotational, and vibrational energy
      effects on the chemical reactivity of water cation H2O(+)(X(2)B1) in the
      collision with deuterium molecule D2. The application of a novel electric-field
      pulsing scheme to the VUV laser PFI-PI ion source has enabled the preparation of
      a rovibrationally selected H2O(+)(X(2)B1; v1 (+)v2 (+)v3 (+); N(+) K a+Kc+) ion
      beam with not only high internal-state selectivity and high intensity but also
      high translational energy resolution. Despite the unfavorable Franck-Condon
      factors, we are able to prepare the excited vibrational states (v1 (+)v2 (+)v3
      (+))=(100) and (020) along with the (000) ground vibrational state, for
      collisional studies, where v1 (+), v2 (+), and v3 (+) represent the symmetric
      stretching, bending, and asymmetric stretching modes of H2O(+)(X(2)B1). We show
      that a range of rotational levels from N(+) K a+Kc+ = 000 to 322, covering a
      rotational energy range of 0-200 cm(-1) of these vibrational states, can also be
      generated for absolute integral cross section (sigma) measurements at center-of
      mass collision energies (Ecms) from thermal energies to 10.00 eV. The Ecm
      dependences of the sigma values are consistent with the prediction of the
      orbiting model, indicating that translational energy significantly hinders the
      chemical reactivity of H2O(+)(X(2)B1). Rotational enhancements are observed at
      Ecm < 0.30 eV for all the three vibrational states, (000), (100), and (020).
      While the sigma values for (100) are found to be only slightly below those for
      (000), the sigma values for (020) are lower than those for (000) and (100) by up
      to 20% at Ecm <= 0.20 eV, indicative of vibrational inhibition at low Ecm by
      excitation of the (020) mode. Rationalizations are proposed for the observed
      rotational enhancements and the bending vibrational inhibition. Rigorous
      theoretical calculations are needed to interpret the wealth of rovibrationally
      selected cross sections obtained in the present study. 

PMID- 23862937
TI  - Origin of the diffuse vibrational signature of a cyclic intramolecular proton
      bond: Anharmonic analysis of protonated 1,8-disubstituted naphthalene ions.
AB  - We analyze the structures and spectral signatures of the cyclic intramolecular
      proton bond, N-H(+)-A, A = O and F, formed when an excess proton is added to
      derivatives of the 1,8-disubstituted naphthalene scaffold. These compounds
      provide a quasi-rigid framework with which to study the spectral complexity often
      associated with the N-H(+)-A entity. Vibrational spectra were obtained by
      monitoring photodissociation of weakly bound H2 adducts of the mass-selected ions
      cooled close to 10 K. Several bands across the 900-3500 cm(-1) spectral range
      were traced to involvement of the bridging proton by their telltale shifts upon
      selective H/D isotopic substitution at that position. We account for the complex
      patterns that occur near the expected locations of the NH stretching fundamentals
      in the context of background levels mixing with a "bright" zero-order state
      through cubic terms in the potential energy expansion. Thus, this system provides
      a detailed picture of one of the mechanisms behind the line broadening often
      displayed by embedded excess protons. It does so in a sufficiently sparse density
      of states regime that many discrete transitions are observed in the vicinity of
      the harmonic stretching transition involving displacement of the trapped proton. 

PMID- 23862938
TI  - Absolute cross sections for O2 dication production by electron impact.
AB  - Direct detection of homonuclear diatomic dications using mass spectrometry has
      the intrinsic inability to distinguish between fragments with the same mass-to
      charge ratio, as is the case of the oxygen molecule. In this work, absolute cross
      sections for the double ionization of the homoisotopic (16)O2 molecule by
      electron impact, in the 30-400 eV energy range, is reported for the first time,
      and show significant discrepancies with previous results, obtained with the
      heteroisotopic (16)O(17)O. The measurements suggest that O2 (++) is mainly
      produced through post-collisional Auger-like deexcitation. 

PMID- 23862939
TI  - Quasiclassical trajectory studies of 18O(3P) + NO2 isotope exchange and reaction
      to O2 + NO on D0 and D1 potentials.
AB  - We report quasiclassical trajectory calculations for the bimolecular reaction
      (18)O((3)P) + NO2 on the recent potential energy surfaces of the ground (D0) and
      first excited (D1) states of NO3 [B. Fu, J. M. Bowman, H. Xiao, S. Maeda, and K.
      Morokuma, J. Chem. Theory. Comput. 9, 893 (2013)]. The branching ratio of isotope
      exchange versus O2 + NO formation, as well as the product angular distributions
      and energy and rovibrational state distributions are presented. The calculations
      are done at the collision energy of relevance to recent crossed beam experiments
      [K. A. Mar, A. L. Van Wyngarden, C.-W. Liang, Y. T. Lee, J. J. Lin, and K. A.
      Boering, J. Chem. Phys. 137, 044302 (2012)]. Very good agreement is achieved
      between the current calculations and these experiments for the branching ratio
      and final translational energy and angular distributions of isotope exchange
      products (16)O((3)P) + NO2 and O2 + NO formation products. The reactant (18)O
      atom results in (18)O(16)O but not N(18)O for the O2 + NO formation product
      channel, consistent with the experiment. In addition, the detailed vibrational
      and rotational state information of diatomic molecules calculated currently for
      the (34)O2 + NO formation channel on D0 and D1 states are in qualitative
      agreement with the previous experimental and theoretical results of the
      photodissociation of NO3 and are consistent with older thermal bimolecular
      kinetics measurements. 

PMID- 23862940
TI  - The quantitative determination of laser-induced molecular axis alignment.
AB  - Experiments in the gas phase usually involve averaging observables over a random
      molecular axis alignment distribution. This deleterious averaging limits insights
      gained by probes of molecular dynamics, but can be overcome by prealigning
      molecular axes using laser-alignment methods. However, the transformation from
      the laboratory frame to the molecular frame of reference requires quantitative
      knowledge of the axis alignment distribution. The latter is often hard to obtain
      directly from experimental data, particularly for polyatomic molecules. Here we
      describe a general maximum-likelihood classification procedure for non-adiabatic
      numerical alignment simulations with free parameters that employs experimental
      data from an alignment-dependent probe. This method delivers (i) the most
      probable molecular frame angular dependence of the probe, and (ii) the most
      likely laboratory frame axis alignment distribution of the sample, each with a
      confidence interval. This procedure was recently used for studies of angle- and
      channel-resolved strong field ionization of 1,3-butadiene in the molecular frame
      [Mikosch et al., Phys. Rev. Lett. 110, 023004 (2013)], used here as an
      illustrative example. 

PMID- 23862941
TI  - Structures, electrophilic properties, and hydrogen bonds of cytidine, uridine,
      and their radical anions: Microhydration effects.
AB  - Structures, electrophilic properties, and hydrogen bonds of the neutral and
      anionic monohydrated nucleoside, (cytidine)H2O, and (uridine)H2O have been
      systematically investigated using density functional theory. Various water
      binding sites were predicted by explicitly considering the optimized monohydrated
      structures. Meanwhile, predictions of electron affinities and vertical detachment
      energies were also carried out to investigate their electrophilic properties. By
      examining the singly occupied molecular orbital and natural population analysis,
      we found the excess negative charge is localized on the cytidine and uridine
      moiety in anionic monohydrates. This may be the reason why the strength of
      hydrogen bonding undergoes an obvious change upon the extra electron attachment.
      Based on the electron density (rho) and reduced density gradient (RDG), we
      present an approach to map and analyze the weak interaction (especially hydrogen
      bond) in monohydrated cytidine and uridine. The scatter plots of RDG versus rho
      allow us to identify the different type interactions. Meanwhile, the maps of the
      gradient isosurfaces show a rich visualization of hydrogen bond, van der Waals
      interaction, and steric effect. 

PMID- 23862942
TI  - Dissipation of alignment in CO2 gas: A comparison between ab initio predictions
      and experiments.
AB  - We present comparisons between measurements and ab initio calculations of the
      dissipation of the nonadiabatic laser-induced alignment in pure CO2 and CO2-He
      gas mixtures. The experiments were made for pressures between 2 and 20 bars at
      295 K by using short non-resonant linearly polarized laser pulses for alignment
      and probe. The calculations are carried, free of any adjusted parameter, using
      refined intermolecular potentials and a requantized Classical Molecular Dynamics
      Simulations approach presented previously but not yet confronted to experiments.
      The results demonstrate that the model accurately reproduces the decays with time
      of both the transient revivals and "permanent" component of the alignment. The
      significant differences observed between the behaviors resulting from CO2-CO2 and
      CO2-He collisions are also well predicted by the model. 

PMID- 23862943
TI  - Site-selective ionization of ethanol dimer under the tunable synchrotron VUV
      radiation and its subsequent fragmentation.
AB  - Site-selective ionization of ethanol dimer and the subsequent fragmentation were
      studied by synchrotron vacuum ultraviolet (VUV) photoionization mass
      spectrometry. With photoionization efficiency spectra measurements and
      theoretical calculations, the detailed mechanisms of the ionization-dissociation
      processes of ethanol dimer under VUV irradiation were explored. In 9.49-10.89 eV
      photon energy range, it was found that the ejection of the highest occupied
      molecular orbital (HOMO) electron from hydrogen bond donor induces a rapid
      barrierless proton-transfer process followed by two competitive dissociation
      channels, generating (C2H5OH)[middle dot]H(+) and CH2O[middle dot](C2H5OH)H(+),
      respectively. The latter comes from a carbon-carbon bond cleavage in the donor.
      While the photon energy is 10.9-11.58 eV, the electron of HOMO-1 of the hydrogen
      bond acceptor, is removed. Besides the dissociation channel to produce C2H5OH and
      C2H5OH(+), a new channel to generate (C2H5OH)[middle dot]CH2OH(+) is opened,
      where the cleavage of the carbon-carbon bond occurs in the acceptor. When the
      photon energy increases to 11.58 eV, the electron from HOMO-2 is ejected. 

PMID- 23862944
TI  - Full-dimensional quantum calculations of the dissociation energy, zero-point, and
      10 K properties of H7+/D7+ clusters using an ab initio potential energy surface.
AB  - Diffusion Monte Carlo (DMC) and path-integral Monte Carlo computations of the
      vibrational ground state and 10 K equilibrium state properties of the H7 (+)/D7
      (+) cations are presented, using an ab initio full-dimensional potential energy
      surface. The DMC zero-point energies of dissociated fragments H5 (+)(D5
      (+))+H2(D2) are also calculated and from these results and the electronic
      dissociation energy, dissociation energies, D0, of 752 +/- 15 and 980 +/- 14 cm(
      1) are reported for H7 (+) and D7 (+), respectively. Due to the known error in
      the electronic dissociation energy of the potential surface, these quantities are
      underestimated by roughly 65 cm(-1). These values are rigorously determined for
      first time, and compared with previous theoretical estimates from electronic
      structure calculations using standard harmonic analysis, and available
      experimental measurements. Probability density distributions are also computed
      for the ground vibrational and 10 K state of H7 (+) and D7 (+). These are
      qualitatively described as a central H3 (+)/D3 (+) core surrounded by "solvent"
      H2/D2 molecules that nearly freely rotate. 

PMID- 23862946
TI  - Synchronous concerted multiple-body photodissociation of oxalyl chloride explored
      by ab initio-based dynamics simulations.
AB  - Photo-induced multiple body dissociation is of fundamental interest in chemistry
      and physics. A description of the mechanism associated with n-body (n >= 3)
      photodissociation has proven to be an intriguing and yet challenging issue in the
      field of chemical dynamics. Oxalyl chloride, (ClCO)2, is the sole molecule
      reported up to date that can undergo four-body dissociation following absorption
      of a single UV photon, with a rich history of mechanistic debate. In the present
      work, the combined electronic structure calculations and dynamics simulations
      have been performed at the advanced level, which provides convincing evidence for
      resolving the mechanistic debate. More importantly, synchronous and asynchronous
      concertedness were explored for the first time for the (ClCO)2 photodissociation,
      which is based on the simulated time constants for the C-C and C-Cl bond
      fissions. Upon photoexcitation of (ClCO)2 to the S1 state, the adiabatic C-C or C
      Cl fission takes place with little possibility. The four-body dissociation to
      2Cl((2)P) and 2CO((1)Sigma) was determined to a dominant channel with its branch
      of ~0.7, while the three-body dissociation to ClCO((2)A(')) + CO((1)Sigma) +
      Cl((2)P) was predicted to play a minor role in the (ClCO)2 photodissociation at
      193 nm. Both the four-body and three-body dissociations are non-adiabatic
      processes, which proceed in a synchronous concerted way as a result of the S1 ->
      S0 internal conversion. There is a little possibility for two-body dissociation
      to occur in the S0 and S1 states. 

PMID- 23862945
TI  - A first principles study of novel one-dimensional organic half-metal vanadium
      cyclooctatetraene wire.
AB  - The structural, electronic, and magnetic properties of one-dimensional vanadium
      cyclooctatetraene[(V-COT)]infinity wire and sandwich clusters are investigated by
      means of density functional theory. It is found that the (V-COT)infinity SMW is
      half-metallic. Through the spin transportation calculations, the system for V-COT
      clusters coupled to gold electrodes performs nearly perfect spin filters. In
      addition, the I-V curve shows obviously negative differential resistance effects.
      These results suggest the potential applications of (V-COT)infinity in
      spintronics. 

PMID- 23862947
TI  - Hard ellipses: Equation of state, structure, and self-diffusion.
AB  - Despite their fundamental and practical interest, the physical properties of hard
      ellipses remain largely unknown. In this paper, we present an event-driven
      molecular dynamics study for hard ellipses and assess the effects of aspect ratio
      and area fraction on their physical properties. For state points in the plane of
      aspect ratio (1 <= k <= 9) and area fraction (0.01 <= phi <= 0.8), we identify
      three different phases, including isotropic, plastic, and nematic states. We
      analyze in detail the thermodynamic, structural, and self-diffusive properties in
      the formed various phases of hard ellipses. The equation of state (EOS) is shown
      for a wide range of aspect ratios and is compared with the scaled particle theory
      (SPT) for the isotropic states. We find that SPT provides a good description of
      the EOS for the isotropic phase of hard ellipses. At large fixed phi, the reduced
      pressure p increases with k in both the isotropic and the plastic phases and,
      interestingly, its dependence on k is rather weak in the nematic phase. We
      rationalize the thermodynamics of hard ellipses in terms of particle motions. The
      static structures of hard ellipses are then investigated both positionally and
      orientationally in the different phases. The plastic crystal is shown to form for
      aspect ratios up to k = 1.4, while appearance of the stable nematic phase starts
      approximately at k = 3. We quantitatively determine the locations of the
      isotropic-plastic (I-P) transition and the isotropic-nematic (I-N) transition by
      analyzing the bond-orientation correlations and the angular correlations,
      respectively. As expected, the I-P transition point is found to increase with k,
      while a larger k leads to a smaller area fraction where the I-N transition takes
      place. Moreover, our simulations strongly support that the two-dimensional
      nematic phase in hard ellipses has only quasi-long-range orientational order. The
      self-diffusion of hard ellipses is further explored and connections are revealed
      between the structure and the self-diffusion. We discuss the relevance of our
      results to the glass transition in hard ellipses. Finally, the results of the
      isodiffusivity lines are evaluated for hard ellipses and we discuss the effect of
      spatial dimension on the diffusive dynamics of hard ellipsoidal particles. 

PMID- 23862948
TI  - Observations on shock induced chemistry of cyclohexane.
AB  - We use double pass absorption spectroscopy to examine shock induced reactions in
      situ in cyclohexane and benzene at pressures up to 33.1 GPa. Reactions in
      cyclohexane begin by 27 GPa and complete by 33.1 GPa. Reactions in benzene are
      observed to begin by 12 GPa and are complete by 18 GPa. Absorption spectra
      indicate that the first reaction in cyclohexane occurs within or near the shock
      front, and that a metastable local equilibrium is reached in the post-shock
      state. A second process may be observed upon reshock at the lower pressures,
      suggesting a new equilibrium is reached post-reshock as well. Absorption bands
      are consistent with the formation of short radicals or fragments upon
      decomposition; however, spectral resolution is too low to confirm this mechanism.

PMID- 23862949
TI  - Debye-type dielectric relaxation in glass-forming 3-methylthio-1-hexanol.
AB  - The dielectric relaxation of a substituted monohydroxy alcohol, 3-methylthio-1
      hexanol, is studied in the highly viscous regime near the glass transition. The
      Debye relaxation is detected in the dielectric spectra showing the slowest and
      strongest relaxation dynamics. The calorimetric and dielectric measurements of
      the liquid and the mixtures with a Debye liquid (2-ethyl-1-hexanol) and a non
      Debye liquid (2-ethylhexylamine) reproduce the dynamic characters of the
      relaxations in monohydroxy alcohols. The Debye relaxation strength and time of 3
      methylthio-1-hexanol do not change much compared with 2-ethyl-1-hexanol, while
      the structural relaxation strength shows a considerable enhancement accompanied
      by an increase in relaxation time, indicative of a reduction in the dynamic
      separation between the Debye and structural relaxations. The experimental results
      allow for the examination of the structural models proposed for the Debye
      relaxation. 

PMID- 23862950
TI  - Vibrational spectra of light and heavy water with application to neutron cross
      section calculations.
AB  - The design of nuclear reactors and neutron moderators require a good
      representation of the interaction of low energy (E < 1 eV) neutrons with hydrogen
      and deuterium containing materials. These models are based on the dynamics of the
      material, represented by its vibrational spectrum. In this paper, we show
      calculations of the frequency spectrum for light and heavy water at room
      temperature using two flexible point charge potentials: SPC-MPG and TIP4P/2005f.
      The results are compared with experimental measurements, with emphasis on
      inelastic neutron scattering data. Finally, the resulting spectra are applied to
      calculation of neutron scattering cross sections for these materials, which were
      found to be a significant improvement over library data. 

PMID- 23862951
TI  - Liquid-vapor equilibrium and surface properties of short rigid chains with one
      long range attractive potential.
AB  - Liquid-vapor coexistence and interfacial properties of short lineal rigid
      vibrating chains with three tangent monomers in two and three dimensions are
      calculated. The effect of the range and position of a long ranged square well
      attractive potential is studied. Orthobaric densities, vapor pressures, surface
      tensions, and interfacial widths are reported. Two types of molecules are
      studied. Chains of three tangent hard sphere monomers and chains of three and
      five tangent hard sphere monomers interacting with a square well attractive
      potential with lambda(*) = lambda/sigma = 1.5 in units of the hard core diameter
      sigma. The results are reported in two and three dimensions. For both types of
      chains, a long ranged square well attractive potential is located at various
      positions in the chain to investigate its effect in the properties of the
      corresponding systems. Results for hard sphere chains are presented for a series
      of different sizes of lambda(*) between 2.5 and 5. For square well chains the
      position in the chain of the long ranged potential has no influence in the
      coexistence and interfacial properties. Critical temperatures increase
      monotonically with respect to lambda(*) and critical densities decrease
      systematically for both types of chains. When the long ranged potential is
      located in the middle monomer of the hard sphere chains no critical point is
      found for lambda(*) < 2.4. No critical point is found when the long ranged
      potential is located in one of the extremes of the hard sphere chains. 

PMID- 23862952
TI  - The water supercooled regime as described by four common water models.
AB  - The temperature scale of simple water models in general does not coincide with
      the natural one. Therefore, in order to make a meaningful evaluation of different
      water models, a temperature rescaling is necessary. In this paper, we introduce a
      rescaling using the melting temperature and the temperature corresponding to the
      maximum of the heat capacity to evaluate four common water models (TIP4P-Ew,
      TIP4P-2005, TIP5P-Ew and Six-Sites) in the supercooled regime. Although all the
      models show the same general qualitative behavior, the TIP5P-Ew appears as the
      best representation of the supercooled regime when the rescaled temperature is
      used. We also analyze, using thermodynamic arguments, the critical nucleus size
      for ice growth. Finally, we speculate on the possible reasons why atomistic
      models do not usually crystalize while the coarse grained mW model do
      crystallize. 

PMID- 23862953
TI  - Molecular modeling of the liquid-vapor interfaces of a multi-component mixture:
      Prediction of the coexisting densities and surface tensions at different
      pressures and gas compositions.
AB  - Two-phase molecular simulations are performed in order to report the interfacial
      tensions and the coexisting densities of a multicomponent mixture (nitrogen +
      methane) + water for five gas compositions in the pressure range of 1-30 MPa at
      298 K. The interfacial tensions are calculated using different definitions and
      the long range corrections of the surface tensions are considered using
      expressions designed for multicomponent mixtures and each definitions. We can
      conclude that the agreement with experiments is quantitative with deviations
      smaller than 5% for the interfacial tensions and 2% for the densities. The
      interfacial region is described in terms of specific arrangements of the gas
      components at the water surface. 

PMID- 23862954
TI  - Resonance Raman and photoluminescence excitation profiles and excited-state
      dynamics in CdSe nanocrystals.
AB  - Resonance Raman excitation profiles for the longitudinal optical (LO) phonon
      fundamental and its first overtone have been measured for organic ligand capped,
      wurtzite form CdSe nanocrystals of ~3.2 nm diameter dissolved in chloroform. The
      absolute differential Raman cross-section for the fundamental is much larger when
      excited at 532 or 543 nm, on the high-frequency side of the lowest-wavelength
      absorption maximum, than for excitation in the 458-476 nm range although the
      absorbance is higher at the shorter wavelengths. That is, the quantum yield for
      resonance Raman scattering is reduced for higher-energy excitation. In contrast,
      the photoluminescence quantum yield is relatively constant with wavelength. The
      optical absorption spectrum and the resonance Raman excitation profiles and
      depolarization dispersion curves are reproduced with a model for the energies,
      oscillator strengths, electron-phonon couplings, and dephasing rates of the
      multiple low-lying electronic excitations. The Huang-Rhys factor for LO phonon in
      the lowest excitonic transition is found to lie in the range S = 0.04-0.14. The
      strong, broad absorption feature about 0.5 eV above the lowest excitonic peak,
      typically labeled as the 1P3/21Pe transition, is shown to consist of at least two
      significant components that vary greatly in the magnitude of their electron
      phonon coupling. 

PMID- 23862955
TI  - Incorporating headgroup structure into the Poisson-Boltzmann model of charged
      lipid membranes.
AB  - Charged lipids often possess a complex headgroup structure with several spatially
      separated charges and internal conformational degrees of freedom. We propose a
      headgroup model consisting of two rod-like segments of the same length that form
      a flexible joint, with three charges of arbitrary sign and valence located at the
      joint and the two terminal positions. One terminal charge is firmly anchored at
      the polar-apolar interface of the lipid layer whereas the other two benefit from
      the orientational degrees of freedom of the two headgroup segments. This
      headgroup model is incorporated into the mean-field continuum Poisson-Boltzmann
      formalism of the electric double layer. For sufficiently small lengths of the two
      rod-like segments a closed-form expression of the charging free energy is
      calculated. For three specific examples--a zwitterionic headgroup with
      conformational freedom and two headgroups that carry an excess charge--we analyze
      and discuss conformational properties and electrostatic free energies.

PMID- 23862956
TI  - Initial reduction of the NiO(100) surface in hydrogen.
AB  - The reduction of NiO in hydrogen, a reaction with many industrial applications,
      has not received sufficient attention from theoretical standpoint because the
      complexity of the material properties and the process present considerable
      computational challenges. We report here the results of a systematic study on the
      hydrogen reduction of an ideal NiO(100) surface that produces a water molecule
      and an NiO(100) surface with an oxygen vacancy, using the Hubbard U corrected
      density functional theory method, with some of the key results verified by the
      hybrid density functional method. The major findings are: (1) the O vacancy in
      the NiO(100) surface slab is stabilized in the subsurface layer, although the
      vacancy is likely to remain on the outermost surface layer because the barrier
      for O vacancy migration from the surface to the second layer is as high as 3.02
      eV; (2) regarding the energetics of hydrogen interaction with the ideal NiO(100)
      surface, water formation, and concomitant reduction of NiO is favored at higher H
      coverage even though surface hydrogenation is energetically more favorable than
      water formation at lower H coverage; (3) kinetically, the pull-off of the surface
      oxygen atom and simultaneous activation of the nearby Ni atoms play key roles in
      hydrogen reduction of NiO(100); and (4) a dual role of hydrogen is revealed as
      both a reactant and a mediator, which reduces the maximum kinetic barrier from
      2.41 eV to 1.86 eV. 

PMID- 23862957
TI  - Understanding the role of vibrations, exact exchange, and many-body van der Waals
      interactions in the cohesive properties of molecular crystals.
AB  - The development and application of computational methods for studying molecular
      crystals, particularly density-functional theory (DFT), is a large and ever
      growing field, driven by their numerous applications. Here we expand on our
      recent study of the importance of many-body van der Waals interactions in
      molecular crystals [A. M. Reilly and A. Tkatchenko, J. Phys. Chem. Lett. 4, 1028
      (2013)], with a larger database of 23 molecular crystals. Particular attention
      has been paid to the role of the vibrational contributions that are required to
      compare experiment sublimation enthalpies with calculated lattice energies,
      employing both phonon calculations and experimental heat-capacity data to provide
      harmonic and anharmonic estimates of the vibrational contributions. Exact
      exchange, which is rarely considered in DFT studies of molecular crystals, is
      shown to have a significant contribution to lattice energies, systematically
      improving agreement between theory and experiment. When the vibrational and exact
      exchange contributions are coupled with a many-body approach to dispersion, DFT
      yields a mean absolute error (3.92 kJ/mol) within the coveted "chemical accuracy"
      target (4.2 kJ/mol). The role of many-body dispersion for structures has also
      been investigated for a subset of the database, showing good performance compared
      to X-ray and neutron diffraction crystal structures. The results show that the
      approach employed here can reach the demanding accuracy of crystal-structure
      prediction and organic material design with minimal empiricism. 

PMID- 23862958
TI  - Numerical simulation of photocurrent generation in bilayer organic solar cells:
      Comparison of master equation and kinetic Monte Carlo approaches.
AB  - Numerical approaches can provide useful information about the microscopic
      processes underlying photocurrent generation in organic solar cells (OSCs). Among
      them, the Kinetic Monte Carlo (KMC) method is conceptually the simplest, but
      computationally the most intensive. A less demanding alternative is potentially
      represented by so-called Master Equation (ME) approaches, where the equations
      describing particle dynamics rely on the mean-field approximation and their
      solution is attained numerically, rather than stochastically. The description of
      charge separation dynamics, the treatment of electrostatic interactions and
      numerical stability are some of the key issues which have prevented the
      application of these methods to OSC modelling, despite of their successes in the
      study of charge transport in disordered system. Here we describe a three
      dimensional ME approach to photocurrent generation in OSCs which attempts to deal
      with these issues. The reliability of the proposed method is tested against
      reference KMC simulations on bilayer heterojunction solar cells. Comparison of
      the current-voltage curves shows that the model well approximates the exact
      result for most devices. The largest deviations in current densities are mainly
      due to the adoption of the mean-field approximation for electrostatic
      interactions. The presence of deep traps, in devices characterized by strong
      energy disorder, may also affect result quality. Comparison of the simulation
      times reveals that the ME algorithm runs, on the average, one order of magnitude
      faster than KMC. 

PMID- 23862959
TI  - Dynamic and dielectric response of charged colloids in electrolyte solutions to
      external electric fields.
AB  - Computer simulations are used to investigate the response of a charged colloid
      and its surrounding microion cloud to an external electric field. Both static
      fields and alternating fields are considered. A mesoscopic simulation method is
      implemented to account in full for hydrodynamic and electrostatic interactions.
      The response of the system can be characterized by two quantities: the mobility
      and the polarizability. Due to the interplay of the electrostatic attraction and
      hydrodynamic drag, the response of the microions close to the colloid surface is
      different from that of the microions far away from the colloid. Both the mobility
      and polarizability exhibit a dependency on the frequency of the external fields,
      which can be attributed to the concentration polarization, the mobility of the
      microions, and the inertia of microions. The effects of the colloidal charge, the
      salt concentration, and the frequency of the external fields are investigated
      systematically. 

PMID- 23862960
TI  - Two cases of reciprocal relations for electric and hydrodynamic currents: A rigid
      polymer in a nano-channel and a polyelectrolyte gel.
AB  - We illustrate an Onsager-type linear response theory of electrohydrodynamic
      coupling for two examples, namely, a long nano-channel blocked partially by a
      rigid polymer and a gel of semi-flexible polyelectrolyte chains. We calculate the
      hydrodynamic and electric currents driven by an external voltage and pressure and
      the corresponding Onsager coefficients for these systems. Our consideration
      clarifies the effect of the electro-osmotic flow on the effective charge of the
      polymer inside the channel. It also makes it possible to explore the dependence
      of the currents through the gel on the electric screening radius and salt
      concentration. 

PMID- 23862961
TI  - Evolution of conductive network and properties of nanorod/polymer composite under
      tensile strain.
AB  - In this work, the conductive network, probability, and percolation threshold of
      nanorod/polymer composites under tensile strain are investigated using the
      molecular dynamics simulation. The internal interactions, including polymer
      polymer, polymer-nanorod, and nanorod-nanorod interactions, are taken into
      account in simulations. In particular, the influence of polymer induced depletion
      force on the orientation of nanorods is analyzed. Under a constant strain, the
      conductive stability firstly declines and then rises with the increasing
      concentration of fillers, and the minimum corresponds to the percolation
      threshold. As strain increases, the result exhibits a strong anisotropy in the
      stability of conductive property.

PMID- 23862962
TI  - Tailoring relaxation time spectrum in soft glassy materials.
AB  - Physical properties of out of equilibrium soft materials depend on time as well
      as deformation history. In this work we propose to transform this major
      shortcoming into gain by applying controlled deformation field to tailor the
      rheological properties. We take advantage of the fact that deformation field of a
      certain magnitude can prevent particles in an aging soft glassy material from
      occupying energy wells up to a certain depth, thereby populating only the deeper
      wells. We employ two soft glassy materials with dissimilar microstructures and
      demonstrate that increase in strength of deformation field while aging leads to
      narrowing of spectrum of relaxation times. We believe that, in principle, this
      philosophy can be universally applied to different kinds of glassy materials by
      changing nature and strength of impetus. 

PMID- 23862964
TI  - Glassy boundary layers vs enhanced mobility in capped polymer films.
AB  - Molecular-dynamics simulations have been carried out for a coarse-grained model
      of a random AB-copolymer confined between two crystalline substrates. The
      strength of substrate-polymer interactions, and the distance between the two
      substrates have been varied in a wide range. For thick films the film-averaged
      segmental mobility decreases for intermediate adsorption strengths, but start to
      increase for very high substrate-polymer attraction strength. We saw that this
      non-monotonic behavior is caused by a very strong heterogeneity of the segmental
      dynamics above the glass-transition temperature: the segmental mobility slows
      down drastically close to adsorbing substrates, but strongly increases in the
      middle part of the film. This effect, and its sensitive dependence on film
      thickness, are explained by finite-size effects in confinement, in combination
      with glassy boundary layers. It is demonstrated that film-averaged mobility as
      often measured cannot be understood without resolving local mobility in space and
      time. 

PMID- 23862963
TI  - Simulations reveal that the HIV-1 gp120-CD4 complex dissociates via complex
      pathways and is a potential target of the polyamidoamine (PAMAM) dendrimer.
AB  - The polyamidoamine (PAMAM) dendrimer prevents HIV-1 entry into target cells in
      vitro. Its mechanism of action, however, remains unclear and precludes the design
      of potent dendrimers targeting HIV-1 entry. We employed steered molecular
      dynamics simulations to examine whether the HIV-1 gp120-CD4 complex is a target
      of PAMAM. Our simulations mimicked single molecule force spectroscopy studies of
      the unbinding of the gp120-CD4 complex under the influence of a controlled
      external force. We found that the complex dissociates via complex pathways and
      defies the standard classification of adhesion molecules as catch and slip bonds.
      When the force loading rate was large, the complex behaved as a slip bond,
      weakening gradually. When the loading rate was small, the complex initially
      strengthened, akin to a catch bond, but eventually dissociated over shorter
      separations than with large loading rates. PAMAM docked to gp120 and destabilized
      the gp120-CD4 complex. The rupture force of the complex was lowered by PAMAM.
      PAMAM disrupted salt bridges and hydrogen bonds across the gp120-CD4 interface
      and altered the hydration pattern of the hydrophobic cavity in the interface. In
      addition, intriguingly, PAMAM suppressed the distinction in the dissociation
      pathways of the complex between the small and large loading rate regimes. Taken
      together, our simulations reveal that PAMAM targets the gp120-CD4 complex at two
      levels: it weakens the complex and also alters its dissociation pathway,
      potentially inhibiting HIV-1 entry. 

PMID- 23862965
TI  - Phase behavior of athermal colloid-star polymer mixtures.
AB  - We investigate the depletion-induced phase behavior of athermal colloid-star
      polymer mixtures on a fine lattice using grand canonical Monte Carlo simulations
      in the "protein limit," that is, where polymer dimensions exceed those of the
      colloid. We consider the influence of the star's functionality, f, the
      macroscopic size ratio, qr = 2Rg, s/sigmac, where Rg, s is the radius of gyration
      of the star and sigmac is the colloid diameter, and the microscopic size ratio, d
      = sigmam/sigmac, where sigmam is the diameter of a Kuhn segment. Recent
      theoretical predictions concerning the qualitative interplay of qr and f in
      determining the phase stability of these mixtures [D. Marzi, C. N. Likos, and B.
      Capone, J. Chem. Phys. 137, 014902 (2012)] in the limit of large f are mostly
      corroborated by our results which span a much lower range of functionalities. Our
      results suggest a direct connection between the phase behavior and the scaling
      regimes of single star structure in the classical Daoud-Cotton (DC) description
      [M. Daoud and J. P. Cotton, J. Phys. 43, 531-538 (1982)]. Using this formalism,
      we define a "low" functionality limit through scaling arguments, for which our
      model provides a mapping of the phase behavior of colloidal mixtures with star
      polymers (f > 2) to linear chains (f = 2). Furthermore, our simulations suggest
      that as qr increases, both the critical monomer and colloid densities tend to a
      constant, finite value for all f; thus, we do not find the prediction by Marzi
      and co-workers of an upper limit to immiscibility (infinite critical densities)
      in terms of qr to be accurate for the stars we have investigated. 

PMID- 23862966
TI  - Adaptively biased sequential importance sampling for rare events in reaction
      networks with comparison to exact solutions from finite buffer dCME method.
AB  - Critical events that occur rarely in biological processes are of great
      importance, but are challenging to study using Monte Carlo simulation. By
      introducing biases to reaction selection and reaction rates, weighted stochastic
      simulation algorithms based on importance sampling allow rare events to be
      sampled more effectively. However, existing methods do not address the important
      issue of barrier crossing, which often arises from multistable networks and
      systems with complex probability landscape. In addition, the proliferation of
      parameters and the associated computing cost pose significant problems. Here we
      introduce a general theoretical framework for obtaining optimized biases in
      sampling individual reactions for estimating probabilities of rare events. We
      further describe a practical algorithm called adaptively biased sequential
      importance sampling (ABSIS) method for efficient probability estimation. By
      adopting a look-ahead strategy and by enumerating short paths from the current
      state, we estimate the reaction-specific and state-specific forward and backward
      moving probabilities of the system, which are then used to bias reaction
      selections. The ABSIS algorithm can automatically detect barrier-crossing
      regions, and can adjust bias adaptively at different steps of the sampling
      process, with bias determined by the outcome of exhaustively generated short
      paths. In addition, there are only two bias parameters to be determined,
      regardless of the number of the reactions and the complexity of the network. We
      have applied the ABSIS method to four biochemical networks: the birth-death
      process, the reversible isomerization, the bistable Schlogl model, and the
      enzymatic futile cycle model. For comparison, we have also applied the finite
      buffer discrete chemical master equation (dCME) method recently developed to
      obtain exact numerical solutions of the underlying discrete chemical master
      equations of these problems. This allows us to assess sampling results
      objectively by comparing simulation results with true answers. Overall, ABSIS can
      accurately and efficiently estimate rare event probabilities for all examples,
      often with smaller variance than other importance sampling algorithms. The ABSIS
      method is general and can be applied to study rare events of other stochastic
      networks with complex probability landscape. 

PMID- 23862967
TI  - Protein electron transfer: Dynamics and statistics.
AB  - Electron transfer between redox proteins participating in energy chains of
      biology is required to proceed with high energetic efficiency, minimizing losses
      of redox energy to heat. Within the standard models of electron transfer, this
      requirement, combined with the need for unidirectional (preferably
      activationless) transitions, is translated into the need to minimize the
      reorganization energy of electron transfer. This design program is, however,
      unrealistic for proteins whose active sites are typically positioned close to the
      polar and flexible protein-water interface to allow inter-protein electron
      tunneling. The high flexibility of the interfacial region makes both the
      hydration water and the surface protein layer act as highly polar solvents. The
      reorganization energy, as measured by fluctuations, is not minimized, but rather
      maximized in this region. Natural systems in fact utilize the broad breadth of
      interfacial electrostatic fluctuations, but in the ways not anticipated by the
      standard models based on equilibrium thermodynamics. The combination of the broad
      spectrum of static fluctuations with their dispersive dynamics offers the
      mechanism of dynamical freezing (ergodicity breaking) of subsets of nuclear modes
      on the time of reaction/residence of the electron at a redox cofactor. The
      separation of time-scales of nuclear modes coupled to electron transfer allows
      dynamical freezing. In particular, the separation between the relaxation time of
      electro-elastic fluctuations of the interface and the time of conformational
      transitions of the protein caused by changing redox state results in dynamical
      freezing of the latter for sufficiently fast electron transfer. The observable
      consequence of this dynamical freezing is significantly different reorganization
      energies describing the curvature at the bottom of electron-transfer free energy
      surfaces (large) and the distance between their minima (Stokes shift, small). The
      ratio of the two reorganization energies establishes the parameter by which the
      energetic efficiency of protein electron transfer is increased relative to the
      standard expectations, thus minimizing losses of energy to heat. Energetically
      efficient electron transfer occurs in a chain of conformationally quenched
      cofactors and is characterized by flattened free energy surfaces, reminiscent of
      the flat and rugged landscape at the stability basin of a folded protein. 

PMID- 23862968
TI  - Note: Molecular architecture dependent hydrogen-bonded motifs, entropy change,
      and dielectric permittivity of alcohols.
AB  - Our previous studies showed that the static permittivity, Es, of some octanol
      isomers first increased on cooling, then decreased, and finally increased
      rapidly, and Es monotonically increased on compression such that the local
      minimum in Es vanished. Thus, while Es is the same at different temperatures and
      pressures, the density differs. To reconcile these findings with thermodynamic
      requirements, we propose that hydrogen bonded ring-dimers of near zero dipole
      moment that form on initial cooling and decrease Es, open to form linear-dimers
      on further cooling (or pressurizing). The H and O atoms at the terminals of the
      linear dimer form hydrogen bonds with the existing monomers and linear chains,
      thus extending the length of the H-bonded chains. This mechanism agrees with the
      enthalpy and entropy of formation of ring-dimer and linear-chain motifs. 

PMID- 23862970
TI  - Aluminum-1,4-cyclohexanedicarboxylates: high-throughput and temperature-dependent
      in situ EDXRD studies.
AB  - The system AlCl3.6H2O/cis-H2CDC/trans-H2CDC/solvent was systematically
      investigated with high-throughput methods to study the influence of the two 1,4
      cyclohexanedicarboxylate isomers (cis- and trans-H2CDC) as flexible aliphatic
      linker molecules on the formation of new crystalline compounds. Using the cis
      isomer, the layered inorganic-organic hybrid compound [Al(OH)(cis-CDC)] (1) is
      formed. The use of trans-H2CDC leads to the microporous MOF [Al(OH)(trans
      CDC)].H2O (2) denoted CAU-13. Its framework is related to the well-known MIL-53,
      which was previously described for trivalent cations and rigid terephthalate
      linker molecules. The crystal structures of 1 and 2 were derived from powder X
      ray diffraction data. Temperature-dependent in situ energy dispersive X-ray
      diffraction (EDXRD) experiments for the synthesis of 2 were carried out at
      HASYLAB, DESY, Hamburg. The kinetic analysis, applying the Gualtieri model to the
      experimental data, revealed Arrhenius activation energies of 76 kJ/mol for both
      the nucleation and the growth process. These values do not differ much from the
      activation energies reported for MOFs with aromatic rigid linker molecules. 

PMID- 23862971
TI  - Small reorganization energies of photoinduced electron transfer between spherical
      fullerenes.
AB  - Rate constants of photoinduced electron transfer between spherical fullerenes
      were determined using triscandium nitride encapsulated C80 fullerene (Sc3N@C80)
      as an electron donor and the triplet excited state of lithium ion-encapsulated
      C60 fullerene (Li(+)@C60) as an electron acceptor in polar and less polar
      solvents by laser flash photolysis measurements. Upon nanosecond laser excitation
      at 355 nm of a benzonitrile (PhCN) solution of Li(+)@C60 and Sc3N@C80, electron
      transfer from Sc3N@C80 to the triplet excited state [(3)(Li(+)@C60)*] occurred to
      produce Sc3N@C80(*+) and Li(+)@C60(*-) (lambda(max) = 1035 nm). The rates of the
      photoinduced electron transfer were monitored by the decay of absorption at
      lambda(max) = 750 nm due to (3)(Li(+)@C60)*. The second-order rate constant of
      electron transfer from Sc3N@C80 to (3)(Li(+)@C60)* was determined to be k(et) =
      1.5 * 10(9) M(-1) s(-1) from dependence of decay rate constant of (3)(Li(+)@C60)*
      on the Sc3N@C80 concentration. The rate constant of back electron transfer from
      Li(+)@C60(*-) to Sc3N@C80(*+) was also determined to be k(bet) = 1.9 * 10(9) M(
      1) s(-1), which is close to be the diffusion limited value in PhCN. Similarly,
      the rate constants of photoinduced electron transfer from C60 to (3)(Li(+)@C60)*
      and from Sc3N@C80 to (3)C60* were determined together with the back electron
      transfer reactions. The driving force dependence of log k(et) and log k(bet) was
      well fitted by using the Marcus theory of outer-sphere electron transfer, in
      which the internal (bond) reorganization energy (lambdai) was estimated by DFT
      calculations and the solvent reorganization energy (lambdas) was calculated by
      the Marcus equation. When PhCN was replaced by o-dichlorobenzene (o-DCB), the
      lambda value was decreased because of the smaller solvation changes of highly
      spherical fullerenes upon electron transfer in a less polar solvent.

PMID- 23862972
TI  - Influence of gender on C-reactive protein, fibrinogen, and erythrocyte
      sedimentation rate in obstructive sleep apnea.
AB  - Inflammation is one of the pathophysiological pathways suggested for the
      development of cardiovascular disease in obstructive sleep apnea (OSA). The
      recurrent nocturnal episodes of hypoxia/reoxygenation observed in patients with
      OSA appear to be partly responsible for the systemic inflammatory response. The
      aim of this study was to investigate the role of inflammation by measuring the C
      reactive protein (CRP) and fibrinogen levels, and erythrocyte sedimentation rate
      (ESR) in the OSA according to gender. This study included 139 apparently healthy
      subjects with newly diagnosed OSA and 27 control subjects who underwent overnight
      polysomnography and routine blood tests. Levels of inflammatory markers (CRP,
      fibrinogen, and ESR) were determined from the blood samples taken in the morning.
      The levels of CRP and fibrinogen were significantly higher in patients than in
      controls (p<0.0001 and p=0.001, respectively). Fibrinogen and ESR were
      significantly higher in the female patients than in the male patients (p<0.0001).
      In female patients, CRP and ESR correlated with time spent at oxygen saturation
      (T%SaO2)<90 (R=0.327, p=0.029 and R=0.301, p=0.05, respectively), T%SaO2<85
      (R=0.482, p=0.001 and R=0.409, p=0.006, respectively), oxygen desaturation index
      (ODI) (R=0.298, p=0.047 and R=0.340, p=0.026, respectively), lowest oxygen
      saturation (SaO2) (R=-0.293, p=0.051 and R=-0.374, p=0.013, respectively), mean
      SaO2 (R=-0.408, p=0.005 and R=-0.385, p=0.011, respectively). In male patients,
      CRP correlated with T%SaO2<90 (R=0.267, p=0.009), T%SaO2<85 (R=0.279, p=0.006),
      mean SaO2 (R=-0.284, p=0.006) and fibrinogen correlated with T%SaO2<90 (R=0.282,
      p=0.028), and mean SaO2 (R=-0.252, p=0.05). In conclusion, increased values of
      systemic inflammatory markers and their correlations with sleep data observed in
      our study support other studies suggesting the possible involvement of
      inflammation in OSA. As this correlation is more apparent in female patients then
      the males, it suggests that there may be a stronger relation between OSA
      development and inflammation in females. Higher levels of CRP, fibrinogen, and
      ESR may result from the combined interactions of obesity, metabolic syndrome
      (MetS) and nocturnal hypoxia.

PMID- 23862973
TI  - Engineered in India--patent law 2.0.

PMID- 23862975
TI  - A new era in noninvasive prenatal testing.

PMID- 23862976
TI  - Enhanced antioxidant effect of trans-resveratrol: potential of binary systems
      with polyethylene glycol and cyclodextrin.
AB  - Trans-resveratrol, a polyphenol extracted from Vitis vinifera, has different
      beneficial effects following its administration on the skin. Here the potential
      use of binary systems to enhance in vitro and in vivo activity of trans
      resveratrol was investigated. Thus the aqueous solubility of trans-resveratrol
      was investigated in the presence of growing concentrations of polyethylene glycol
      (PEG) or beta-cyclodextrin (betaCD) as solubilizing excipients. Then, the solid
      dispersion of trans-resveratrol with PEG or inclusion complexes trans
      resveratrol/betaCD were prepared and characterised by different methods.
      Cytotoxicity and inhibition of reactive oxygen species (ROS) following H2O2
      challenge in the presence of trans-resveratrol, alone or associated to the
      excipients, was evaluated on human keratinocyte HaCaT cell line. Both the trans
      resveratrol-containing binary systems induced significant reduction of H2O2
      induced ROS production, especially in the case of betaCD that was selected for
      the following phase of the study. Thus, the effect of a cream containing trans
      resveratrol, alone or associated to betaCD, on different skin parameters such as
      corneometry, colorimetry and elastometry, was evaluated on human volunteers. All
      patients showed a visible improvement of clinical conditions with a remarkable
      decrease of aging signs, but this effect was higher of the hemi face treated with
      the betaCD-containing formulation versus formulation containing trans-resveratrol
      alone.

PMID- 23862977
TI  - Formulation and characterization of ethylcellulose microparticles containing .L
      alanyl- L-glutamine peptide.
AB  - CONTEXT: The L-alanyl-L-glutamine peptide (AGP) has been effective to promote
      acute glycemia recovery during long-term insulin-induced hypoglycemia (IIH), and
      the oral administration of AGP is suggested to prevent prolonged hypoglycemia,
      such as nocturnal hypoglycemia. OBJECTIVE: Considering the ability of AGP on
      glycemia recovery and AGP's fast metabolism, the aim of current study was to
      obtain and characterize ethylcellulose microparticles to deliver the drug for a
      prolonged time. MATERIALS AND METHODS: Microparticles were prepared by simple and
      double emulsification/hardening method and characterized by scanning electron
      microscopy, thermogravimetry (TG), differential scanning calorimetry (DSC),
      Fourier transform infra-red (FTIR) and FT-Raman spectroscopy and in vitro
      release. RESULTS AND DISCUSSION: Spherical structures with a mean diameter
      between 9.30 um and 13.19 um were formed. TG analysis showed that the thermal
      stability of AGP was even more increased by encapsulation with ethylcellulose. In
      addition, TG, DSC, FTIR and FT-Raman analyses proved that AGP was encapsulated in
      a molecular way. Higher values of encapsulation efficiency were observed for the
      microparticles prepared by double emulsification (57.83-83.67%) than for those
      prepared by simple emulsification (18.37%). However, the last ones could release
      the peptide in a quicker and more extensive manner than those prepared by double
      emulsification. CONCLUSION: For the first time, microparticles containing AGP
      were developed and exhibited prolonged in vitro release as well as protection to
      the drug, and it could be considered as a dosage form for patients who suffer
      from insulin-induced hypoglycemia and/or nocturnal hypoglycemia.

PMID- 23862974
TI  - Mutations in DSTYK and dominant urinary tract malformations.
AB  - BACKGROUND: Congenital abnormalities of the kidney and the urinary tract are the
      most common cause of pediatric kidney failure. These disorders are highly
      heterogeneous, and the etiologic factors are poorly understood. METHODS: We
      performed genomewide linkage analysis and whole-exome sequencing in a family with
      an autosomal dominant form of congenital abnormalities of the kidney or urinary
      tract (seven affected family members). We also performed a sequence analysis in
      311 unrelated patients, as well as histologic and functional studies. RESULTS:
      Linkage analysis identified five regions of the genome that were shared among all
      affected family members. Exome sequencing identified a single, rare, deleterious
      variant within these linkage intervals, a heterozygous splice-site mutation in
      the dual serine-threonine and tyrosine protein kinase gene (DSTYK). This variant,
      which resulted in aberrant splicing of messenger RNA, was present in all affected
      family members. Additional, independent DSTYK mutations, including nonsense and
      splice-site mutations, were detected in 7 of 311 unrelated patients. DSTYK is
      highly expressed in the maturing epithelia of all major organs, localizing to
      cell membranes. Knockdown in zebrafish resulted in developmental defects in
      multiple organs, which suggested loss of fibroblast growth factor (FGF)
      signaling. Consistent with this finding is the observation that DSTYK colocalizes
      with FGF receptors in the ureteric bud and metanephric mesenchyme. DSTYK
      knockdown in human embryonic kidney cells inhibited FGF-stimulated
      phosphorylation of extracellular-signal-regulated kinase (ERK), the principal
      signal downstream of receptor tyrosine kinases. CONCLUSIONS: We detected
      independent DSTYK mutations in 2.3% of patients with congenital abnormalities of
      the kidney or urinary tract, a finding that suggests that DSTYK is a major
      determinant of human urinary tract development, downstream of FGF signaling.
      (Funded by the National Institutes of Health and others.).

PMID- 23862978
TI  - Recent structural advances of beta1 and beta2 adrenoceptors yield keys for ligand
      recognition and drug design.
AB  - Because they represent attractive drug targets, adrenoceptors have been widely
      studied. Recent progress in structural data of beta-adrenoceptors allows us to
      understand and predict key interactions in ligand recognition and receptor
      activation. Nevertheless, an important aspect of this process has only begun to
      be explored: the stabilization of a conformational state of these receptors upon
      contact with a ligand and the capacity of a ligand to influence receptor
      conformation through allosteric modulation, biased signaling, and selectivity.
      The aim of the present Perspective is to identify the well-defined orthosteric
      binding site and possible allosteric sites and to analyze the importance of the
      ligand-receptor interaction in the stabilization of certain receptor
      conformations. For this purpose, we have reviewed recent advances made through
      the use of X-ray data from ligand-beta-adrenoceptor (including ADRB1 and ADRB2)
      crystal structures. Most importantly, implications in the medicinal chemistry
      field are explored in relation to drug design. 

PMID- 23862979
TI  - Osmotic virial coefficients of hydroxyethyl starch from aqueous hydroxyethyl
      starch-sodium chloride vapor pressure osmometry.
AB  - Hydroxyethyl starch (HES) is an important industrial additive in the paper,
      textile, food, and cosmetic industries and has been shown to be an effective
      cryoprotectant for red blood cells; however, little is known about its
      thermodynamic solution properties. In many applications, in particular those in
      biology, HES is used in an aqueous solution with sodium chloride (NaCl). The
      osmotic virial solution thermodynamics approach accurately captures the
      dependence of osmolality on molality for many types of solutes in aqueous
      systems, including electrolytes, sugars, alcohols, proteins, and starches.
      Elliott et al. proposed mixing rules for the osmotic virial equation to be used
      for osmolality of multisolute aqueous solutions [Elliott, J. A. W.; et al. J.
      Phys. Chem. B 2007, 111, 1775-1785] and recently applied this approach to the
      fitting of one set of aqueous HES-NaCl solution data reported by Jochem and
      Korber [Cryobiology 1987, 24, 513-536], indicating that the HES osmotic virial
      coefficients are dependent on HES-to-NaCl mass ratios. The current study reports
      new aqueous HES-NaCl vapor pressure osmometry data which are analyzed using the
      osmotic virial equation. HES modifications were measured after dialysis (membrane
      cut off: 10,000 g/mol) and freeze-drying using vapor pressure osmometry at
      different mass ratios of HES to NaCl for HES up to 50% and NaCl up to 25% with
      three different HES modifications (weight average molecular weights
      [g/mol]/degree of substitution: 40,000/0.5; 200,000/0.5; 450,000/0.7). Equations
      were then fit to the data to provide a model for HES osmotic virial coefficient
      dependence on mass ratio of HES to NaCl. The osmolality data of the three HES
      modifications were accurately described over a broad range of HES-to-NaCl mass
      ratios using only four parameters, illustrating the power of the osmotic virial
      approach in analyzing complex data sets. As expected, the second osmotic virial
      coefficients increase with molecular weight of the HES and increase with HES-to
      NaCl mass ratio.

PMID- 23862981
TI  - Ipilimumab and vemurafenib: two different routes for targeting melanoma.
AB  - Melanoma, a malignant tumor of melanocytes, causes the majority (75%) of all skin
      cancer-related deaths. The overall efficacy of different anti-cancer therapies on
      metastatic melanoma is quite limited, due to its high resistance to all forms of
      conventional treatments, including chemotherapy, radiotherapy and immunotherapy,
      leading to low patient survival rates. The present review identifies possible
      strategies for the treatment of advanced melanoma and describes two novel agents,
      Ipilimumab and Vemurafenib, which may now be useful for clinical practice.
      Ipilimumab, a humanized, IgG1 monoclonal antibody, acts through immune-modulation
      since it blocks cytotoxic T-lymphocyte- associated antigen-4 (CTLA-4), producing
      favourable antitumor immune system responses and reducing tolerance to tumor
      associated antigens. Vemurafenib is a novel oral small-molecule kinase inhibitor
      with high selectivity and efficacy toward a specific mutated oncogenic BRAF
      signalling mediator. The mechanism of action of Vemurafenib involves selective
      inhibition of the mutated BRAF(V600E) kinase that leads to reduced signalling
      through the aberrant MAPK pathway. However, as patients commonly develop
      Vemurafenib resistance, clinical trials of Vemurafenib in combination with
      Ipilimumab or other targeted or cytotoxic chemotherapeutic agents may provide
      more effective regimens with longterm clinical benefits, emphasizing the
      importance of simultaneously targeting several pathways. As both drugs had only
      modest effects on median survival, new therapeutic combinations are needed, such
      as BRAF inhibitors with MEK inhibitors or combinations of immunomodulators and
      pathway inhibitors. Such strategies should have the potential of maximizing
      antitumor effect while minimizing and improving clinical benefit. Nevertheless,
      these two new agents open a promising view into an effective management of
      melanoma. 

PMID- 23862982
TI  - Anti-inflammatory and antinociceptive activities of Homalium letestui.
AB  - CONTEXT: Homalium letestui Pellegr (Flacourtiaceae) is used in various decoctions
      traditionally by the Ibibios of the Niger Delta of Nigeria to treat stomach
      ulcer, malaria and other inflammatory diseases, as well as an aphrodisiac.
      OBJECTIVE: To investigate the anti-inflammatory and antinociceptive activities of
      the stem extract of the plant. MATERIALS AND METHODS: The ethanol stem extract
      (500, 750, 1000 mg/kg, i.p.) of H. letestui was investigated for anti
      inflammatory activity using carrageenan, egg albumin-induced and xylene-induced
      ear edema models and analgesic activity using acetic acid-induced writhing,
      formalin-induced paw licking and thermal-induced pain models. The ethanol extract
      was administered to the animals orally, 30 min to 1 h depending on the model,
      before induction of inflammation/pain. The LD50 was also determined. GC-MS
      analysis of dichloromethane fraction was carried out. RESULTS: The extract caused
      a significant (p < 0.05-0.001) reduction of inflammation induced by carrageenan
      (8.3-70.0%), egg albumin (10.0-71.42%) and xylene (39.39-84.84%). The extract
      also reduced significantly (p < 0.05-0.001) pain induced by acetic acid (44.22
      73.65%), formalin (55.89-79.21%) and hot plate (93.0-214.5%). The LD50 was
      determined to be 4.38 +/- 35.72 g/kg. DISCUSSION AND CONCLUSION: The results of
      this study suggest that the ethanol stem extract of H. letestui possesses anti
      inflammatory and analgesic properties which may in part be mediated through the
      chemical constituents of the plant as revealed by the GC-MS.

PMID- 23862980
TI  - Preconditioning thermal therapy: flipping the switch on IL-6 for anti-tumour
      immunity.
AB  - Cancer immunotherapy aims to generate long-lived, tumour-specific adaptive
      immunity to limit dysregulated tumour progression and metastasis. Tumour
      vasculature has emerged as a critical checkpoint controlling the efficacy of
      immunotherapy since it is the main access point for cytotoxic T cells to reach
      tumour cell targets. Therapeutic success has been particularly challenging to
      achieve because of the local, cytokine-rich inflammatory milieu that drives a pro
      tumourigenic programme supporting the growth and survival of malignant cells.
      Here, we focus on recent evidence that systemic thermal therapy can switch the
      activities of the inflammatory cytokine, interleukin-6 (IL-6), to a predominantly
      anti-tumourigenic function that promotes anti-tumour immunity by mobilising T
      cell trafficking in the recalcitrant tumour microenvironment.

PMID- 23862983
TI  - Experimentally quantifying small-molecule bond activation using valence-to-core X
      ray emission spectroscopy.
AB  - This work establishes the ability of valence-to-core X-ray emission spectroscopy
      (XES) to serve as a direct probe of N2 bond activation. A systematic series of
      iron-N2 complexes has been experimentally investigated and the energy of a
      valence-to-core XES peak was correlated with N-N bond length and stretching
      frequency. Computations demonstrate that, in a simple one-electron picture, this
      peak arises from the N2 2s2s sigma* orbital, which becomes less antibonding as
      the N-N bond is weakened and broken. Changes as small as 0.02 A in the N-N bond
      length may be distinguished using this approach. The results thus establish
      valence-to-core XES as an effective probe of small molecule activation, which
      should have broad applicability in transition-metal mediated catalysis. 

PMID- 23862984
TI  - Canonical thermal pure quantum state.
AB  - A thermal equilibrium state of a quantum many-body system can be represented by a
      typical pure state, which we call a thermal pure quantum (TPQ) state. We
      construct the canonical TPQ state, which corresponds to the canonical ensemble of
      the conventional statistical mechanics. It is related to the microcanonical TPQ
      state, which corresponds to the microcanonical ensemble, by simple analytic
      transformations. Both TPQ states give identical thermodynamic results, if both
      ensembles do, in the thermodynamic limit. The TPQ states corresponding to other
      ensembles can also be constructed. We have thus established the TPQ formulation
      of statistical mechanics, according to which all quantities of statistical
      mechanical interest are obtained from a single realization of any TPQ state. We
      also show that it has great advantages in practical applications. As an
      illustration, we study the spin-1/2 kagome Heisenberg antiferromagnet. 

PMID- 23862985
TI  - Quantum speed limit for non-Markovian dynamics.
AB  - We derive a Margolus-Levitin-type bound on the minimal evolution time of an
      arbitrarily driven open quantum system. We express this quantum speed limit time
      in terms of the operator norm of the nonunitary generator of the dynamics. We
      apply these results to the damped Jaynes-Cummings model and demonstrate that the
      corresponding bound is tight. We further show that non-Markovian effects can
      speed up quantum evolution and therefore lead to a smaller quantum speed limit
      time. 

PMID- 23862986
TI  - Entanglement's benefit survives an entanglement-breaking channel.
AB  - Entanglement is essential to many quantum information applications, but it is
      easily destroyed by quantum decoherence arising from interaction with the
      environment. We report the first experimental demonstration of an entanglement
      based protocol that is resilient to loss and noise which destroy entanglement.
      Specifically, despite channel noise 8.3 dB beyond the threshold for entanglement
      breaking, eavesdropping-immune communication is achieved between Alice and Bob
      when an entangled source is used, but no such immunity is obtainable when their
      source is classical. The results prove that entanglement can be utilized
      beneficially in lossy and noisy situations, i.e., in practical scenarios. 

PMID- 23862987
TI  - Disentangling sources of anomalous diffusion.
AB  - We show that some important properties of subdiffusion of unknown origin
      (including ones of mixed origins) can be easily assessed when finding the
      "fundamental moment" of the corresponding random process, i.e., the one which is
      additive in time. In subordinated processes, the index of the fundamental moment
      is inherited from the parent process and its time dependence from the leading
      one. In models of a particle's motion in disordered potentials, the index is
      governed by the structural part of the disorder while the time dependence is
      given by its energetic part. 

PMID- 23862988
TI  - Imitating chemical motors with optimal information motors.
AB  - To induce transport, detailed balance must be broken. A common mechanism is to
      bias the dynamics with a thermodynamic fuel, such as chemical energy. An
      intriguing, alternative strategy is for a Maxwell demon to effect the bias using
      feedback. We demonstrate that these two different mechanisms lead to distinct
      thermodynamics by contrasting a chemical motor and information motor with
      identical dynamics. To clarify this difference, we study both models within one
      unified framework, highlighting the role of the interaction between the demon and
      the motor. This analysis elucidates the manner in which information is
      incorporated into a physical system. 

PMID- 23862989
TI  - Limits on the dependence of the fine-structure constant on gravitational
      potential from white-dwarf spectra.
AB  - We propose a new probe of the dependence of the fine-structure constant alpha on
      a strong gravitational field using metal lines in the spectra of white-dwarf
      stars. Comparison of laboratory spectra with far-UV astronomical spectra from the
      white-dwarf star G191-B2B recorded by the Hubble Space Telescope Imaging
      Spectrograph gives limits of Deltaalpha/alpha=(4.2+/-1.6)*10(-5) and (-6.1+/
      5.8)*10(-5) from FeV and NiV spectra, respectively, at a dimensionless
      gravitational potential relative to Earth of Deltaphi~5*10(-5). With better
      determinations of the laboratory wavelengths of the lines employed these results
      could be improved by up to 2 orders of magnitude.

PMID- 23862990
TI  - Anisotropies in the gravitational wave background from preheating.
AB  - We investigate the anisotropies in the gravitational wave (GW) background
      produced at preheating after inflation. Using lattice field theory simulations of
      a massless preheating model, we show that the GW amplitude depends sensitively on
      the value of the decay product field chi coupled to the inflaton phi, with the
      only requisite that chi is light during inflation. We find a strong anisotropy in
      the amplitude of the GW background on large angular scales, the details of which
      strongly depend on the reheating dynamics. We expect similar conclusions for a
      wide class of inflationary models with light scalar fields. If future direct
      detection GW experiments are capable of detecting the GW produced by preheating,
      they should also be able to detect this effect. This could eventually provide a
      powerful way to distinguish between different inflationary and preheating
      scenarios.

PMID- 23862991
TI  - Universal Landau pole.
AB  - Our understanding of quantum gravity suggests that at the Planck scale the usual
      geometry loses its meaning. If so, the quest for grand unification in a large non
      Abelian group naturally endowed with the property of asymptotic freedom may also
      lose its motivation. Instead, we propose a unification of all fundamental
      interactions at the Planck scale in the form of a universal Landau pole, at which
      all gauge couplings diverge. The Higgs quartic coupling also diverges while the
      Yukawa couplings vanish. The unification is achieved with the addition of
      fermions with vector gauge couplings coming in multiplets and with hypercharges
      identical to those of the standard model. The presence of these particles also
      prevents the Higgs quartic coupling from becoming negative, thus avoiding the
      instability (or metastability) of the standard model vacuum. 

PMID- 23862992
TI  - Determining triple gauge boson couplings from Higgs data.
AB  - In the framework of effective Lagrangians with the SU(2)(L)*U(1)(Y) symmetry
      linearly realized, modifications of the couplings of the Higgs field to the
      electroweak gauge bosons are related to anomalous triple gauge couplings (TGCs).
      Here, we show that the analysis of the latest Higgs boson production data at the
      LHC and Tevatron give rise to strong bounds on TGCs that are complementary to
      those from direct TGC analysis. We present the constraints on TGCs obtained by
      combining all available data on direct TGC studies and on Higgs production
      analysis.

PMID- 23862994
TI  - Photon signals from quarkyonic matter.
AB  - We calculate the bremsstrahlung photon spectrum emitted from dynamically evolving
      "quarkyonic" matter and compare this spectrum with that of a high chemical
      potential quark-gluon plasma as well as to a hadron gas. We find that the
      transverse momentum distribution and the harmonic coefficient is markedly
      different in the three cases. The transverse momentum distribution of quarkyonic
      matter can be fit with an exponential but is markedly steeper than the
      distribution expected for the quark-gluon plasma or a hadron gas, even at the
      lower temperatures expected in the critical point region. The quarkyonic elliptic
      flow coefficient fluctuates randomly from event to event and within the same
      event at different transverse momenta. The latter effect, which can be explained
      by the shape of quark wave functions within quarkyonic matter, might be
      considered as a quarkyonic matter signature, provided that the initial
      temperature is low enough that the quarkyonic regime dominates over deconfinement
      effects and the reaction-plane flow can be separated from the fluctuating
      component. 

PMID- 23862993
TI  - Luminosity-independent measurement of the proton-proton total cross section at
      ?s=8 TeV.
AB  - The TOTEM collaboration has measured the proton-proton total cross section at
      ?s=8 TeV using a luminosity-independent method. In LHC fills with dedicated beam
      optics, the Roman pots have been inserted very close to the beam allowing the
      detection of ~90% of the nuclear elastic scattering events. Simultaneously the
      inelastic scattering rate has been measured by the T1 and T2 telescopes. By
      applying the optical theorem, the total proton-proton cross section of (101.7+/
      2.9) mb has been determined, well in agreement with the extrapolation from lower
      energies. This method also allows one to derive the luminosity-independent
      elastic and inelastic cross sections: sigma(el)=(27.1+/-1.4) mb;
      sigma(inel)=(74.7+/-1.7) mb.

PMID- 23862995
TI  - Non-Gaussian fluctuations and non-Markovian effects in the nuclear fusion
      process: Langevin dynamics emerging from quantum molecular dynamics simulations.
AB  - Macroscopic parameters as well as precise information on the random force
      characterizing the Langevin-type description of the nuclear fusion process around
      the Coulomb barrier are extracted from the microscopic dynamics of individual
      nucleons by exploiting the numerical simulation of the improved quantum molecular
      dynamics. It turns out that the dissipation dynamics of the relative motion
      between two fusing nuclei is caused by a non-Gaussian distribution of the random
      force. We find that the friction coefficient as well as the time correlation
      function of the random force takes particularly large values in a region a little
      bit inside of the Coulomb barrier. A clear non-Markovian effect is observed in
      the time correlation function of the random force. It is further shown that an
      emergent dynamics of the fusion process can be described by the generalized
      Langevin equation with memory effects by appropriately incorporating the
      microscopic information of individual nucleons through the random force and its
      time correlation function. 

PMID- 23862996
TI  - Constrained-path quantum Monte Carlo approach for the nuclear shell model.
AB  - A new quantum Monte Carlo approach is proposed to investigate low-lying states of
      nuclei within the shell model. The formalism relies on a variational symmetry
      restored wave function to guide the underlying Brownian motion. Sign or phase
      problems that usually plague quantum Monte Carlo fermionic simulations are
      controlled by constraining stochastic paths through a fixed-node-like
      approximation. Exploratory results in the sd and pf valence spaces with realistic
      effective interactions are presented. They prove the ability of the scheme to
      yield nearly exact yrast spectroscopies for both even- and odd-mass nuclei. 

PMID- 23862997
TI  - Accurate and efficient approximation to the optimized effective potential for
      exchange.
AB  - We devise an efficient practical method for computing the Kohn-Sham exchange
      correlation potential corresponding to a Hartree-Fock electron density. This
      potential is almost indistinguishable from the exact-exchange optimized effective
      potential (OEP) and, when used as an approximation to the OEP, is vastly better
      than all existing models. Using our method one can obtain unambiguous, nearly
      exact OEPs for any reasonable finite one-electron basis set at the same low cost
      as the Krieger-Li-Iafrate and Becke-Johnson potentials. For all practical
      purposes, this solves the long-standing problem of black-box construction of OEPs
      in exact-exchange calculations. 

PMID- 23862998
TI  - Precision frequency metrology of helium 2(1)S(0)->2(1)P(1) transition.
AB  - We report a precision frequency measurement of the (4)He 2(1)S(0)->2(1)P(1)
      transition at 2058 nm. The saturated absorption spectroscopy is performed in a rf
      discharge sealed-off cell with a volume Bragg grating-based Tm:Ho:YLF laser. The
      absolute transition frequency measured using a fiber optical frequency comb is
      145 622 892 822 (183) kHz with a relative uncertainty of 1.3*10(-9). Our result
      is ten times more precise than current best theoretical calculations and is in
      reasonable agreement with the calculated values. However, the ionization energy
      of the 2(1)P(1) state, derived from our result and other precisely measured
      transitions, shows a discrepancy of approximately 3.5sigma with the most precise
      atomic theory. We have also determined the isotope shift between (3)He and (4)He
      to be 4248.7 (5.3) MHz, which is more precise than the previous measurement by
      one order of magnitude.

PMID- 23863000
TI  - Intensity fluctuations of waves in random media: what is the semiclassical limit?
AB  - Waves traveling through weakly random media are known to be strongly affected by
      their corresponding ray dynamics, in particular in forming linear freak waves.
      The ray intensity distribution, which, e.g., quantifies the probability of freak
      waves is unknown, however, and a theory of how it is approached in an appropriate
      semiclassical limit of wave mechanics is lacking. We show that this limit is not
      the usual limit of small wavelengths, but that of decoherence. Our theory, which
      can describe the intensity distribution for an arbitrary degree of coherence is
      relevant to a wide range of physical systems, as decoherence is omnipresent in
      real systems. 

PMID- 23862999
TI  - Ejection of quasi-free-electron pairs from the helium-atom ground state by single
      photon absorption.
AB  - We investigate the single-photon double ionization of helium at photon energies
      of 440 and 800 eV. We observe doubly charged ions with close to zero momentum
      corresponding to electrons emitted back to back with equal energy. These slow
      ions are the unique fingerprint of an elusive quasifree photon double ionization
      mechanism predicted by Amusia et al. nearly four decades ago [J. Phys. B 8, 1248
      (1975)]. It results from the nondipole part of the electromagnetic interaction.
      Our experimental data are supported by calculations performed using the
      convergent close-coupling and time-dependent close-coupling methods. 

PMID- 23863001
TI  - Reviving oscillations in coupled nonlinear oscillators.
AB  - By introducing a processing delay in the coupling, we find that it can
      effectively annihilate the quenching of oscillation, amplitude death (AD), in a
      network of coupled oscillators by switching the stability of AD. It revives the
      oscillation in the AD regime to retain sustained rhythmic functioning of the
      networks, which is in sharp contrast to the propagation delay with the tendency
      to induce AD. This processing delay-induced phenomenon occurs both with and
      without the propagation delay. Further this effect is rather general from two
      coupled to networks of oscillators in all known scenarios that can exhibit AD,
      and it has a wide range of applications where sustained oscillations should be
      retained for proper functioning of the systems. 

PMID- 23863002
TI  - Capillary deformations of bendable films.
AB  - We address the partial wetting of liquid drops on ultrathin solid sheets resting
      on a deformable foundation. Considering the membrane limit of sheets that can
      relax compression through wrinkling at negligible energetic cost, we revisit the
      classical theory for the contact of liquid drops on solids. Our calculations and
      experiments show that the liquid-solid-vapor contact angle is modified from the
      Young angle, even though the elastic bulk modulus (E) of the sheet is so large
      that the ratio between the surface tension gamma and E is of molecular size. This
      finding indicates a new elastocapillary phenomenon that stems from the high
      bendability of very thin elastic sheets rather than from material softness. We
      also show that the size of the wrinkle pattern that emerges in the sheet is fully
      predictable, thus resolving a puzzle in modeling "drop-on-a-floating-sheet"
      experiments and enabling a quantitative, calibration-free use of this setup for
      the metrology of ultrathin films. 

PMID- 23863003
TI  - Water drops dancing on ice: how sublimation leads to drop rebound.
AB  - Drop rebound is a spectacular event that appears after impact on hydrophobic or
      superhydrophobic surfaces but can also be induced through the so-called
      Leidenfrost effect. Here we demonstrate that drop rebound can also originate from
      another physical phenomenon, the solid substrate sublimation. Through drop impact
      experiments on a superhydrophobic surface, a hot plate, and solid carbon dioxide
      (commonly known as dry ice), we compare drop rebound based on three different
      physical mechanisms, which apparently share nothing in common
      (superhydrophobicity, evaporation, and sublimation), but lead to the same rebound
      phenomenon in an extremely wide temperature range, from 300  degrees C down to
      even below -79  degrees C. The formation and unprecedented visualization of an
      air vortex ring around an impacting drop are also reported.

PMID- 23863004
TI  - Effect of a marginal inclination on pattern formation in a binary liquid mixture
      under thermal stress.
AB  - Convective motions in a fluid layer are affected by its orientation with respect
      to the gravitational field. We investigate the long-term stability of a thermally
      stressed layer of a binary liquid mixture and show that pattern formation is
      strongly affected by marginal inclinations as small as a few milliradians. At
      small Rayleigh numbers, the mass transfer is dominated by the induced large scale
      shear flow, while at larger Rayleigh numbers, it is dominated by solutal
      convection. At the transition, the balance between the solutal and shear flows
      gives rise to drifting columnar flows moving in opposite directions along
      parallel lanes in a superhighway configuration. 

PMID- 23863005
TI  - Hardening and termination of long-duration gamma rays detected prior to
      lightning.
AB  - We report the first observation of 3-30 MeV prolonged gamma-ray emission that was
      abruptly terminated by lightning. The gamma-ray detection was made during winter
      thunderstorms on December 30, 2010, by the Gamma-Ray Observation of Winter
      Thunderclouds experiment carried out in a coastal area along the Sea of Japan.
      The gamma-ray flux lasted for less than 3 min, continuously hardening closer to
      the lightning occurrence. The hardening at energies of 3-10 MeV energies was most
      prominent. The gamma-ray flux abruptly ceased less than 800 ms before the
      lightning flash that occurred over 5 km away from the experimental site. In
      addition, we observed a clear difference in the duration of the 3-10 MeV gamma
      rays and those >10 MeV, suggesting that the area of >10 MeV gamma-ray emission is
      considerably smaller than that of the lower-energy gamma rays. This work may give
      a manifestation that a local region emitting prolonged gamma rays connects with a
      distant region to initiate lightning.

PMID- 23863006
TI  - Ideal gas behavior of a strongly coupled complex (dusty) plasma.
AB  - In a laboratory, a two-dimensional complex (dusty) plasma consists of a low
      density ionized gas containing a confined suspension of Yukawa-coupled plastic
      microspheres. For an initial crystal-like form, we report ideal gas behavior in
      this strongly coupled system during shock-wave experiments. This evidence
      supports the use of the ideal gas law as the equation of state for soft crystals
      such as those formed by dusty plasmas. 

PMID- 23863007
TI  - Generating high-brightness electron beams via ionization injection by transverse
      colliding lasers in a plasma-wakefield accelerator.
AB  - The production of ultrabright electron bunches using ionization injection
      triggered by two transversely colliding laser pulses inside a beam-driven plasma
      wake is examined via three-dimensional particle-in-cell simulations. The
      relatively low intensity lasers are polarized along the wake axis and overlap
      with the wake for a very short time. The result is that the residual momentum of
      the ionized electrons in the transverse plane of the wake is reduced, and the
      injection is localized along the propagation axis of the wake. This minimizes
      both the initial thermal emittance and the emittance growth due to transverse
      phase mixing. Simulations show that ultrashort (~8 fs) high-current (0.4 kA)
      electron bunches with a normalized emittance of 8.5 and 6 nm in the two planes,
      respectively, and a brightness of 1.7*10(19) A rad(-2) m(-2) can be obtained for
      realistic parameters.

PMID- 23863008
TI  - Induced emission of Alfven waves in inhomogeneous streaming plasma: implications
      for solar corona heating and solar wind acceleration.
AB  - The results of a self-consistent kinetic model of heating the solar corona and
      accelerating the fast solar wind are presented for plasma flowing in a nonuniform
      magnetic field configuration of near-Sun conditions. The model is based on a
      scale separation between the large transit or inhomogeneity scales and the small
      dissipation scales. The macroscale instability of the marginally stable particle
      distribution function compliments the resonant frequency sweeping dissipation of
      transient Alfven waves by their induced emission in inhomogeneous streaming
      plasma that provides enough energy for keeping the plasma temperature decaying
      not faster than r(-1) in close agreement with in situ heliospheric observations.

PMID- 23863009
TI  - dc-Magnetic-field generation in unmagnetized shear flows.
AB  - The generation of dc magnetic fields in unmagnetized electron-ion shear flows is
      shown to be associated to either initial thermal effects or the onset of electron
      scale shear instabilities, in particular the cold Kelvin-Helmholtz instability.
      This mechanism, intrinsic to shear gradients on the electron scale, is described
      through a kinetic model that predicts the growth and the saturation of the dc
      field in both scenarios. The theoretical results are confirmed by
      multidimensional particle-in-cell simulations, demonstrating the formation of
      long-lived magnetic fields (t~100's omega(pi)(-1)) along the full longitudinal
      extent of the shear layer, with a typical transverse width of
      ?[gamma(0)]c/omega(pe), reaching magnitudes
      eB(dc)/m(e)comega(pe)~beta(0)?[gamma(0)] for an initial sharp shear. The case of
      an initial smooth shear is also discussed.

PMID- 23863010
TI  - Ion runaway in lightning discharges.
AB  - Runaway ions can be produced in plasmas with large electric fields, where the
      accelerating electric force is augmented by the low mean ionic charge due to the
      imbalance between the number of electrons and ions. Here we derive an expression
      for the high-energy tail of the ion distribution function in lightning discharges
      and investigate the energy range that the ions can reach. We also estimate the
      corresponding energetic proton and neutron production due to fusion reactions. 

PMID- 23863011
TI  - Phase diagram and structural diversity of a family of truncated cubes: degenerate
      close-packed structures and vacancy-rich states.
AB  - Using Monte Carlo simulations and free-energy calculations, we determine the
      phase diagram of a family of truncated hard cubes, where the shape evolves
      smoothly from a cube via a cuboctahedron to an octahedron. A remarkable diversity
      in crystal phases and close-packed structures is found, including a fully
      degenerate crystal structure, several plastic crystals, as well as vacancy
      stabilized crystal phases, all depending sensitively on the precise particle
      shape. Our results illustrate the intricate relation between phase behavior and
      building-block shape, and can guide future experimental studies on polyhedral
      shaped nanoparticles. 

PMID- 23863012
TI  - Highly ordered noncrystalline metallic phase.
AB  - We report the characterization of a unique metallic glass that, during rapid
      cooling of an Al-Fe-Si melt, forms by nucleation, followed by growth normal to a
      moving interface between the solid and melt with partitioning of the chemical
      elements. We determine experimentally that this is not a polycrystalline
      composite with nanometer-sized grains, and conclude that this may be a new kind
      of structure: an atomically ordered, isotropic, noncrystalline solid, possessing
      no long-range translational symmetry. 

PMID- 23863013
TI  - Direct observation of interstitial dislocation loop coarsening in alpha-iron.
AB  - Interstitial loop coarsening by Ostwald ripening can provide insight into single
      point defects but is very difficult to observe in alpha-iron and many other
      metals where nanoscale vacancy clusters dissociate and annihilate loops. We show
      that by implanting helium in the samples at a carefully chosen energy, it is
      possible to observe Ostwald ripening of loops by transmission electron microscopy
      during in situ isochronal annealings. This coarsening of loops results in a sharp
      increase of the mean loop radius at around 850 K. Using cluster dynamics
      simulations, we demonstrate that loops evolve due to vacancy emission and that
      such experiments give a robust estimation of the sum of the formation and
      migration free energies of vacancies. In particular, our results are in good
      agreement with self-diffusion experiments and confirm that entropic contributions
      are large for the vacancy in alpha-iron. 

PMID- 23863014
TI  - Rheology across the zero-temperature jamming transition.
AB  - Many soft-matter systems show a transition between fluidlike and mechanically
      solidlike states when the volume fraction of the material, e.g., particles,
      drops, or bubbles is increased. Using an emulsion as a model system with a
      precisely controllable volume fraction, we show that the entire mechanical
      behavior in the vicinity of the jamming point can be understood if the mechanical
      transition is assumed to be analogous to a phase transition. We find power-law
      scalings in the distance to the jamming point, in which the parameters and
      exponents connect the behavior above and below jamming. We propose a simple two
      state model with heterogeneous dynamics to describe the transition between jammed
      and mobile states. The model reproduces the steady-state and creep rheology and
      relates the power-law exponents to diverging microscopic time scales. 

PMID- 23863015
TI  - Reverse epitaxy of Ge: ordered and faceted surface patterns.
AB  - Normal incidence ion irradiation at elevated temperatures, when amorphization is
      prevented, induces novel nanoscale patterns of crystalline structures on
      elemental semiconductors by a reverse epitaxial growth mechanism: on Ge surfaces
      irradiation at temperatures above the recrystallization temperature of 250 
      degrees C leads to self-organized patterns of inverse pyramids. Checkerboard
      patterns with fourfold symmetry evolve on the Ge (100) surface, whereas on the Ge
      (111) surface, isotropic patterns with a sixfold symmetry emerge. After high
      fluence irradiations, these patterns exhibit well-developed facets. A
      deterministic nonlinear continuum equation accounting for the effective surface
      currents due to an Ehrlich-Schwoebel barrier for diffusing vacancies reproduces
      remarkably well our experimental observations.

PMID- 23863016
TI  - Ultrafast charge recombination in a photoexcited Mott-Hubbard insulator.
AB  - We present a calculation of the recombination rate of the excited holon-doublon
      pairs based on the two-dimensional model relevant for undoped cuprates, which
      shows that fast processes, observed in pump-probe experiments on Mott-Hubbard
      insulators in the picosecond range, can be explained even quantitatively with the
      multimagnon emission. The precondition is the existence of the Mott-Hubbard bound
      exciton of the s-type. We find that its decay is exponentially dependent on the
      Mott-Hubbard gap and on the magnon energy, with a small prefactor, which can be
      traced back to strong correlations and consequently large exciton-magnon
      coupling. 

PMID- 23863017
TI  - Competing topological and Kondo insulator phases on a honeycomb lattice.
AB  - We investigate the competition between the spin-orbit interaction of itinerant
      electrons and their Kondo coupling with local moments densely distributed on the
      honeycomb lattice. We find that the model at half-filling displays a quantum
      phase transition between topological and Kondo insulators at a nonzero Kondo
      coupling. In the Kondo-screened case, tuning the electron concentration can lead
      to a new topological insulator phase. The results suggest that the heavy-fermion
      phase diagram contains a new regime with a competition among topological, Kondo
      coherent and magnetic states, and that the regime may be especially relevant to
      Kondo lattice systems with 5d-conduction electrons. Finally, we discuss the
      implications of our results in the context of the recent experiments on SmB(6)
      implicating the surface states of a topological insulator, as well as the
      existing experiments on the phase transitions in SmB(6) under pressure and in
      CeNiSn under chemical pressure.

PMID- 23863018
TI  - Suppression of the Hanle effect in organic spintronic devices.
AB  - We study carrier spin transport under a transverse magnetic field in organic
      structures. In organics, carriers are localized polarons and charge transport is
      via polaron hopping. Spin transport, however, can utilize the exchange coupling
      between localized polarons, which can be much faster than polaron hopping and
      rapidly increases with the carrier density. Consequently, a much stronger
      magnetic field is needed to modify spin polarization and observe the Hanle effect
      than estimated from the carrier mobility, which can help with the understanding
      of recent Hanle measurements in organic spin valves. The exchange-induced spin
      transport also greatly mitigates the conductivity mismatch between ferromagnets
      and organics, enabling spin injection into organics. 

PMID- 23863019
TI  - Topological magnetoelectric effect decay.
AB  - We address the influence of realistic disorder and finite doping on the effective
      magnetic monopole induced near the surface of an ideal topological insulator (TI)
      by currents that flow in response to a suddenly introduced external electric
      charge. We show that when the longitudinal conductivity sigma(xx)=g(e(2)/h)?0,
      the apparent position of a magnetic monopole initially retreats from the TI
      surface at speed v(M)=alphacg, where alpha is the fine structure constant and c
      is the speed of light. For the particular case of TI surface states described by
      a massive Dirac model, we further find that the temperature T=0 Hall currents
      vanish when the external potential is screened.

PMID- 23863020
TI  - Organic pi-conjugated copolymers as molecular charge qubits.
AB  - We propose a design for molecular charge qubits based on pi-conjugated block
      copolymers and determine their electronic structure as well as their vibrational
      active modes. By tuning the length of the oligomers, the tunnel coupling in the
      charge qubit and its decoherence properties due to molecular vibrations can be
      chemically engineered. Coherent oscillations result with quality factors of up to
      10(4) at room temperature. In turn, the molecular vibrational spectrum induces
      strong non-Markovian electronic effects which support the survival of quantum
      coherence.

PMID- 23863021
TI  - RKKY interaction and intrinsic frustration in non-Fermi-liquid metals.
AB  - We study the RKKY interaction in non-Fermi-liquid metals. We find that the RKKY
      interaction mediated by some non-Fermi-liquid metals can be of much longer range
      than for a Fermi liquid. The oscillatory nature of the RKKY interaction thus
      becomes more important in such non-Fermi liquids, and gives rise to enhanced
      frustration when the spins form a lattice. Frustration suppresses the magnetic
      ordering temperature of the lattice spin system. Furthermore, we find that the
      spin system with a longer range RKKY interaction can be described by the
      Brazovskii model, where the ordering wave vector lies on a higher dimensional
      manifold. Strong fluctuations in such a model lead to a first-order phase
      transition and/or glassy phase. This may explain some recent experiments where
      glassy behavior was observed in stoichiometric heavy fermion material close to a
      ferromagnetic quantum critical point. 

PMID- 23863022
TI  - Universal behavior of the Shannon mutual information of critical quantum chains.
AB  - We consider the Shannon mutual information of subsystems of critical quantum
      chains in their ground states. Our results indicate a universal leading behavior
      for large subsystem sizes. Moreover, as happens with the entanglement entropy,
      its finite-size behavior yields the conformal anomaly c of the underlying
      conformal field theory governing the long-distance physics of the quantum chain.
      We study analytically a chain of coupled harmonic oscillators and numerically the
      Q-state Potts models (Q=2, 3, and 4), the XXZ quantum chain, and the spin-1
      Fateev-Zamolodchikov model. The Shannon mutual information is a quantity easily
      computed, and our results indicate that for relatively small lattice sizes, its
      finite-size behavior already detects the universality class of quantum critical
      behavior. 

PMID- 23863023
TI  - MnSb2O6: a polar magnet with a chiral crystal structure.
AB  - Structural and magnetic chiralities are found to coexist in a small group of
      materials in which they produce intriguing phenomenologies such as the recently
      discovered Skyrmion phases. Here, we describe a previously unknown manifestation
      of this interplay in MnSb(2)O(6), a trigonal oxide with a chiral crystal
      structure. Unlike all other known cases, the MnSb(2)O(6) magnetic structure is
      based on corotating cycloids rather than helices. The coupling to the structural
      chirality is provided by a magnetic axial vector, related to the so-called vector
      chirality. We show that this unique arrangement is the magnetic ground state of
      the symmetric-exchange Hamiltonian, based on ab initio theoretical calculations
      of the Heisenberg exchange interactions, and is stabilized by out-of-plane
      anisotropy. MnSb(2)O(6) is predicted to be multiferroic with a unique
      ferroelectric switching mechanism.

PMID- 23863024
TI  - Morphotropic phase boundaries in ferromagnets: Tb(1-x)Dy(x)Fe2 alloys.
AB  - The structure and properties of the ferromagnet Tb(1-x)Dy(x)Fe(2) are explored
      through the morphotropic phase boundary (MPB) separating ferroic phases of
      differing symmetry. Our synchrotron data support a first order structural
      transition, with a broadening MPB width at higher temperatures. The optimal point
      for magnetomechanical applications is not centered on the MPB but lies on the
      rhombohedral side, where the high striction of the rhombohedral majority phase
      combines with the softened anisotropy of the MPB. We compare our findings with
      single ion crystal field theory and with ferroelectric MPBs, where the
      controlling energies are different.

PMID- 23863025
TI  - Lifetimes of antiferromagnetic magnons in two and three dimensions: experiment,
      theory, and numerics.
AB  - A high-resolution neutron spectroscopic technique is used to measure momentum
      resolved magnon lifetimes in the prototypical two- and three-dimensional
      antiferromagnets Rb(2)MnF(4) and MnF(2), over the full Brillouin zone and a wide
      range of temperatures. We rederived theories of the lifetime resulting from
      magnon-magnon scattering, thereby broadening their applicability beyond
      asymptotically small regions of wave vector and temperature. Corresponding
      computations, combined with a small contribution reflecting collisions with
      domain boundaries, yield excellent quantitative agreement with the data.
      Comprehensive understanding of magnon lifetimes in simple antiferromagnets
      provides a solid foundation for current research on more complex magnets.

PMID- 23863026
TI  - Formation of isolated Zn vacancies in ZnO single crystals by absorption of
      ultraviolet radiation: a combined study using positron annihilation,
      photoluminescence, and mass spectroscopy.
AB  - Positron annihilation spectra reveal isolated zinc vacancy (V(Zn)) creation in
      single-crystal ZnO exposed to 193-nm radiation at 100 mJ/cm(2) fluence. The
      appearance of a photoluminescence excitation peak at 3.18 eV in irradiated ZnO is
      attributed to an electronic transition from the V(Zn) acceptor level at ~100 meV
      to the conduction band. The observed V(Zn) density profile and hyperthermal Zn(+)
      ion emission support zinc vacancy-interstitial Frenkel pair creation by exciting
      a wide 6.34 eV Zn-O antibonding state at 193-nm photon-a novel photoelectronic
      process for controlled V(Zn) creation in ZnO.

PMID- 23863027
TI  - Energy dissipation in driven granular matter in the absence of gravity.
AB  - We experimentally investigate the energy dissipation rate in sinusoidally driven
      boxes which are partly filled by granular material under conditions of
      weightlessness. We identify two different modes of granular dynamics, depending
      on the amplitude of driving, A. For intense forcing, A>A(0), the material is
      found in the collect-and-collide regime where the center of mass of the granulate
      moves synchronously with the driven container, while for weak forcing, A<A(0),
      the granular material exhibits gaslike behavior. Both regimes correspond to
      different dissipation mechanisms, leading to different scaling with amplitude and
      frequency of the excitation and with the mass of the granulate. For the collect
      and-collide regime, we explain the dependence on frequency and amplitude of the
      excitation by means of an effective one-particle model. For both regimes, the
      results may be collapsed to a single curve characterizing the physics of granular
      dampers.

PMID- 23863028
TI  - Li+ transport in poly(ethylene oxide) based electrolytes: neutron scattering,
      dielectric spectroscopy, and molecular dynamics simulations.
AB  - The dynamics of Li(+) transport in polyethylene oxide (PEO) and lithium
      bis(trifluoromethanesulfonyl)imde mixtures are investigated by combining neutron
      spin-echo (NSE) and dielectric spectroscopy with molecular dynamics (MD)
      simulations. The results are summarized in a relaxation time map covering wide
      ranges of temperature and time. The temperature dependence of the dc conductivity
      and the dielectric alpha relaxation time is found to be identical, indicating a
      strong coupling between both. The relaxation times obtained from the NSE
      measurements at 0.05 A(-1)<q<0.2 A(-1) are of similar magnitude as the relaxation
      time of Li(+) predicted by MD simulation. Our results suggest that the
      characteristic live times of the ions within the oxygen cages are mainly
      determined by the alpha relaxation that corresponds to local segmental motions of
      polymers, to a much lesser extent by the main chain relaxation, and not at all by
      the beta relaxation or other faster processes. It is the first time decisive
      experimental evidence for a microscopic picture of the Li ion transportation
      process is shown in which the PEO chain forms EO cages over several monomer units
      and the Li ion "jump" from cage to cage. The role of the backbone of the polymer
      is discussed and contributes signifcantly to the Li ion transportation process.
      Moreover, detailed characteristic length and time scales of the Li(+) transport
      process in this polymer electrolyte are identified and interpreted.

PMID- 23863029
TI  - Comment on "Observation of the deexcitation of the (229m)Th nuclear isomer".

PMID- 23863030
TI  - Comment on "Intense superradiant x rays from a compact source using a nanocathode
      array and emittance exchange".

PMID- 23863031
TI  - Graves et al. reply:.

PMID- 23863032
TI  - Identification of inhibitors of the antibiotic-resistance target New Delhi
      metallo-beta-lactamase 1 by both nanoelectrospray ionization mass spectrometry
      and ultrafiltration liquid chromatography/mass spectrometry approaches.
AB  - Mass spectrometry-based platforms have gained increasing success in discovery of
      ligands bound to therapeutic targets as drug candidates. We established both a
      nanoelectrospray ionization mass spectrometry (nanoESI-MS) assay and an
      ultrafiltration liquid chromatography/mass spectrometry (LC/MS) assay to identify
      new ligands for New Delhi metallo-beta-lactamase 1 (NDM-1), responsible for
      worldwide antibiotic resistance. To alleviate nonspecific binding of hydrophobic
      compounds and eliminate false positives typically encountered in the indirect
      LC/MS-based assay, we introduced a blocking protein in the control, which
      remarkably enhances the selectivity and accuracy of the indirect approach. Side
      by-side comparison of the two MS-based approaches for the first time further
      reveals unique advantages of the indirect approach, including better
      reproducibility and tolerance of interference. Moreover, the success of fishing
      out a potent ligand from a mixture of small-molecule fragments demonstrates great
      potential of the indirect LC/MS-based approach for constructing a robust
      screening platform against combinatorial libraries or natural product extracts.
      More importantly, by combining the results of MS-based analyses, enzymatic
      activity assay, competition experiments, and structural simulation, we discovered
      a new compound as a promising drug candidate targeting NDM-1. 

PMID- 23863033
TI  - What about platelet counts in clozapine users?
AB  - OBJECTIVE: In this retrospective study, we aimed to evaluate platelet changes in
      patients taking clozapine for a variety of psychiatric disorders and hypothesized
      that there would be any changes in the course of the treatment. METHODS:
      Diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders
      4(th) edition. Forty-three patients, with the mean age of 36.23 +/- 6.35 years
      were included into final analysis. Morning venous blood samples were used for
      platelet counts. Correlation analyses were performed between platelet counts and
      clozapine doses. RESULTS: Paired t test did not reveal a significant change in
      platelet counts at the end visit compared to those of first assessment (p>0.05).
      Seven (17.9%) of 39 patients had platelet count below 180000 per cubic millimeter
      at least one time during their clozapine use. In five of these patients, the
      platelet count returned to a level above 180000 per cubic millimeter, without any
      dose change or other interventions. On the other hand, as for the issue of
      increased platelet count, results demonstrated that seven (17.9%) had platelet
      count above 400000 per cubic millimeter at least one time during clozapine use.
      CONCLUSION: The present investigation revealed that platelet changes beyond WBC
      changes should be taken into consideration when using clozapine. Clinicians
      should be aware of the deviations from absolute threshold values.

PMID- 23863034
TI  - Emerging evidence that radial is safer than femoral percutaneous coronary
      intervention in subjects with ST segment elevation myocardial infarction.
AB  - Bleeding complications in patients with acute coronary syndromes are a
      significant predictor of mortality. Trans-radial approach (TRA) is a promising
      strategy to reduce bleedings in patients undergoing invasive coronary procedures.
      Recently, two multicentre prospective randomized trials aimed to test whether
      TRA, compared to trans-femoral approach (TFA), may improve clinical outcome in
      patients with ST-elevation myocardial infarction: the RIFLE STEAC and STEMI
      RADIAL. In the RIFLE STEACS, the primary endpoint of 30-day NACEs occurred in 68
      patients (13.6%) in the TRA arm and 105 patients (21.0%) in the TFA arm (p =
      0.003). In particular, compared with TFA, TRA was associated with significantly
      lower rates of cardiac mortality (5.2% vs. 9.2% , p = 0.020), bleeding (7.8% vs.
      12.2%, p = 0.026), and shorter hospital stay (5 days, [range, 4 to 7 days]; vs. 6
      [range, 5 to 8 days]; p = 0.03). In the STEMI-RADIAL, the primary endpoint of
      major bleeding or access site complications occurred in 7.2 percent of the TFA
      patients and 1.4 percent of the TRA patients (p=0.0001). The rate of MACE at 30
      days was 4.2 percent in the TFA group, and 3.5 percent in the TRA group (p=0.7).
      The results of two recent trials support the systematic adoption of TRA instead
      of TFA approach to improve the clinical outcome of STEMI patients. In the present
      paper, we overview the results of these two trials and put them in the context of
      previous scientific evidences collected in this field. 

PMID- 23863035
TI  - Role of 3-methyl-2,4-nonanedione in the flavor of aged red wines.
AB  - GC-MS in chemical ionization mode (CI) was used as a simple, sensitive method for
      assaying 3-methyl-2,4-nonanedione (MND) in 67 red wines. MND content was shown to
      be lower in nonoxidized red wines and higher in oxidized red wines, that is,
      systematically exceeding the perception threshold (62 ng/L). Concentrations up to
      340 ng/L in the most oxidized red wines were also evidenced. According to these
      quantitative data, the presence of MND alone was shown to modify significantly
      the flavor of the red wine as evaluated from fresh fruit flavor in red wine
      without MND to aromatic expression of rancio in wines with elevated
      concentrations (308.9 ng/L). Incidence of oxygen on its formation was also
      investigated. For the first time, elevated concentrations of this compound in
      various wines were demonstrated, that is, white, rose, botrytized wines, and
      fortified wines made with over-ripened grapes. The lowest levels (2.9 ng/L) were
      found in nonoxidized white wines, whereas the highest levels were found in
      oxidized botrytized wines (293.8 ng/L). These results tend to demonstrate that
      MND is in general a good marker of oxidation in wines made with a maceration step
      between the skin and the pulp. These preliminary results provide a new analytical
      explanation of what is known in enology as the "vin de garde" concept. 

PMID- 23863037
TI  - Synthesis, structure, and properties of two Zintl phases around the composition
      SrLiAs.
AB  - Two atomic arrangements were found near the equiatomic composition in the
      strontium-lithium-arsenic system. Orthorhombic o-SrLiAs was synthesized by
      reaction of elemental components at 950  degrees C, followed by annealing at 800 
      degrees C and subsequent quenching in water. The hexagonal modification h-SrLi(1
      x)As was obtained from annealing of o-SrLiAs at 550  degrees C in dynamic vacuum.
      The structures of both phases were determined by single-crystal X-ray
      diffraction: o-SrLiAs, structure type TiNiSi, space group Pnma, Pearson symbol
      oP12, a = 7.6458(2) A, b = 4.5158(1) A, c = 8.0403(3) A, V = 277.61(2) A(3), R(F)
      = 0.028 for 558 reflections; h-SrLi(1-x)As, structure type ZrBeSi, space group
      P6(3)/mmc, Pearson symbol hP6, a = 4.49277(9) A, c = 8.0970(3) A, V = 141.54(1)
      A(3), RF = 0.026 for 113 reflections. The analysis of the electron density within
      the framework of the quantum theory of atoms in molecules revealed a charge
      transfer according to the Sr(1.3+)Li(0.8+)As(2.1-), in agreement with the
      electronegativities of the individual elements. The electron localizability
      indicator distribution indicated the formation of a 3D anionic framework [LiAs]
      in o-SrLiAs and a rather 2D anionic framework [LiAs] in h-SrLi(1-x)As. Magnetic
      susceptibility measurements point to a diamagnetic character of both phases,
      which verifies the calculated electronic density of states.

PMID- 23863036
TI  - Effect of omega-3 dietary supplements with different oxidation levels in the
      lipidic profile of women: a randomized controlled trial.
AB  - The oxidation level of omega-3 fatty acid supplements commercialized in capsules
      may be a risk to consumers' health. For this purpose, we have designed a single
      blind, parallel-group, randomized controlled trial in which 52 women
      participated. Volunteers were randomly distributed into three groups consuming:
      (1) less oxidized oil pills, (2) highly oxidized oil pills and (3) no capsules.
      All groups consumed a fish-rich diet. Circulating glucose, total cholesterol,
      triglycerides and glutamic pyruvic transaminase were determined at the beginning
      and end (30 days) of the study. As a result, the ingestion of less oxidized omega
      3 supplements reduced circulating triglyceride and cholesterol levels, as opposed
      to the highly oxidized omega-3 capsules, which had a negative effect on
      cholesterol levels. In conclusion, the level of oxidation of the supplements is a
      key factor in controlling circulating lipid profile. Therefore, manufacturers
      must pay attention to the quality of the prime product prior to encapsulation.

PMID- 23863038
TI  - Dietary exposure and health risk assessment for 11 minerals and trace elements in
      Yaounde: the Cameroonian Total Diet Study.
AB  - Dietary exposure to 11 elements was assessed by the Total Diet Study (TDS)
      method. Sixty-four pooled samples representing 96.5% of the diet in Yaounde,
      Cameroon, were prepared as consumed before analysis. Consumption data were
      sourced from a household budget survey. Dietary exposures were compared with
      nutritional or health-based guidance values (HBGV) and to worldwide TDS results.
      Elevated prevalence of inadequate intake was estimated for calcium (71.6%), iron
      (89.7%), magnesium (31.8%), zinc (46.9%) and selenium (87.3%). The percentage of
      the study population exceeding the tolerable upper intake levels was estimated as
      <3.2% for calcium, iron, magnesium, zinc and cobalt; 19.1% of the population
      exceeded the HBGV for sodium. No exceedance of the HBGV for inorganic mercury was
      predicted in the population. The margin of exposure ranged from 0.91 to 25.0 for
      inorganic arsenic depending on the reference point. The "Fish" food group was the
      highest contributor to intake for calcium (65%), cobalt (32%) and selenium (96%).
      This group was the highest contributor to the exposure to total arsenic (71%) and
      organic mercury (96%). The "Cereals and cereal products" highly contributed to
      iron (26%), zinc (26%) and chromium (25%) intakes. The "Tubers and starches"
      highly contributed to magnesium (39%) and potassium (52%) intakes. This study
      highlights the dietary deficiency of some essential elements and a low dietary
      exposure to toxic elements in Yaounde.

PMID- 23863039
TI  - Adsorption of single Li and the formation of small Li clusters on graphene for
      the anode of lithium-ion batteries.
AB  - We analyzed the adsorption of Li on graphene in the context of anodes for lithium
      ion batteries (LIBs) using first-principles methods including van der Waals
      interactions. We found that although Li can reside on the surface of defect-free
      graphene under favorable conditions, the binding is much weaker than to graphite
      and the concentration on a graphene surface is not higher than in graphite. At
      low concentration, Li ions spread out on graphene because of Coulomb repulsion.
      With increased Li content, we found that small Li clusters can be formed on
      graphene. Although this result suggests that graphene nanosheets can conceivably
      have a higher ultimate Li capacity than graphite, it should be noted that such
      nanoclusters can potentially nucleate Li dendrites, leading to failure. The
      implications for nanostructured carbon anodes in batteries are discussed. 

PMID- 23863040
TI  - Medical conditions in geriatric hoarding disorder patients.
AB  - Hoarding disorder (HD) in late life is associated with increased risk for fire,
      falling, poor sanitary conditions, disability, and health risks. However,
      research on the health status of individuals with HD is limited. Hoarding
      symptoms and the resulting clutter may exacerbate health conditions and lead to
      improper management of medical illnesses. OBJECTIVE: The purpose of this study is
      to characterize the health status of older adults with hoarding. The rates of
      medical conditions will be compared to a non-psychiatric peer group. METHOD: 72
      older adults with HD and 25 age matched normal controls, completed a medical
      conditions checklist, symptom severity measures (i.e., UCLA Hoarding Severity
      Scale, UHSS; Saving Inventory-Revised, SI-R) and a measure capturing activities
      of daily living (activities of daily living-hoarding, ADL-H). RESULTS: Older
      adults with HD (n = 72) reported significantly more health conditions compared to
      their non-psychiatric peers (n = 25). Hoarding severity significantly predicted
      the total number of medical conditions. Further, the vast majority of HD patients
      reported at least one medical condition. CONCLUSION: This is alarming given that
      hoarding patients utilized health services less than typical for older adults.
      Given the health status of older adults with HD, interventions should target the
      prevention and management of medical conditions.

PMID- 23863041
TI  - Testing an integrated behavioural and biomedical model of disability in N-of-1
      studies with chronic pain.
AB  - BACKGROUND: Previous research has supported an integrated biomedical and
      behavioural model explaining activity limitations. However, further tests of this
      model are required at the within-person level, because while it proposes that the
      constructs are related within individuals, it has primarily been tested between
      individuals in large group studies. We aimed to test the integrated model at the
      within-person level. METHOD: Six correlational N-of-1 studies in participants
      with arthritis, chronic pain and walking limitations were carried out. Daily
      measures of theoretical constructs were collected using a hand-held computer
      (PDA), the activity was assessed by self-report and accelerometer and the data
      were analysed using time-series analysis. RESULTS: The biomedical model was not
      supported as pain impairment did not predict activity, so the integrated model
      was supported partially. Impairment predicted intention to move around, while
      perceived behavioural control (PBC) and intention predicted activity. PBC did not
      predict activity limitation in the expected direction. CONCLUSIONS: The
      integrated model of disability was partially supported within individuals,
      especially the behavioural elements. However, results suggest that different
      elements of the model may drive activity (limitations) for different individuals.
      The integrated model provides a useful framework for understanding disability and
      suggests interventions, and the utility of N-of-1 methodology for testing theory
      is illustrated.

PMID- 23863042
TI  - Fabrication of three-dimensional nanostructured titania materials by prism
      holographic lithography and the sol-gel reaction.
AB  - We present a simple, easy method for fabricating high-quality titania inverted
      replicas of 3D holographically featured structures. A combination of single-prism
      holographic lithography and sol-gel chemistry was used to prepare 3D titania
      inverse structures with flat and completely open surfaces without the use of
      additional postprocessing steps, such as reactive ion etching, ion-beam milling,
      and/or polishing steps. A hydrophobic, stable liquid titania precursor
      facilitated the complete infiltration of the precursor into the hydrophobic 3D SU
      8 polymer template, which produced very uniform high-quality titania inverse
      structures. Although the degree of film shrinkage during the calcination process
      was large (~34%), the optical strength of the 3D titania inverse photonic
      crystals doubled because of the high-refractive-index contrast. Compared to
      titania inverse opal structures, the filling fraction (~27%) of titania materials
      has been doubled. This is the first work to fabricate titania inverse photonic
      crystals with a high filling fraction by utilizing prism holographic lithography
      and the sol-gel chemistry reaction of a stable titania precursor. The X-ray
      diffraction patterns indicated the presence of a crystalline anatase or rutile
      phase depending on the calcination temperature. 

PMID- 23863043
TI  - One-pot synthesis of dihydropyrano [2,3-c]chromenes via a three-component
      reaction in aqueous media.
AB  - An efficient protocol for the synthesis of dihydropyrano [2,3-c] chromenes
      derivatives by one-pot threecomponent reaction of aromatic aldehydes,
      malononitrile or methyl cyanoacetate, and 4-hydroxy coumarin has been developed
      using catalytic amount (10%) of three different catalysts piperidine, triethyl
      amine, and natrium carbonate in aqueous media. The present protocol has
      significant features such as easy set-up and work-up, environmentally benign,
      high yields, short reaction times. 

PMID- 23863044
TI  - To what extent should waterpipe tobacco smoking become a public health priority?
AB  - BACKGROUND: Waterpipe tobacco smoking (WTS) popularity is increasing world-wide,
      and health effects are emerging in the light of evidence that WTS is perceived by
      users as less harmful than cigarette smoking. However, there remains a paucity of
      available evidence from which to draw firm conclusions about its public health
      significance. AIMS: This narrative review aims to summarize WTS literature to
      date to inform tobacco control specialists and health-care professionals about
      this phenomenon and help them to assess whether or not WTS should become a public
      health priority. METHODS: Standard electronic databases as well as conference
      proceedings and personal libraries were searched in English, French and Arabic
      with inclusive terminology for the variety of names given to WTS. FINDINGS:
      Waterpipe smoke contains significant levels of toxins, some of which are known to
      be carcinogenic to humans. Recent epidemiological trends have established an
      increasing prevalence of WTS in the Middle East and the United States,
      particularly among adolescents. It is used commonly across multiple ethnicities
      and both genders with less of a social gradient than cigarette smoking. Attitudes
      and beliefs have been researched widely and several reasons for believing it is
      less harmful than cigarette smoking include water filtration and social
      acceptability. A wide range of diseases have been associated with WTS, but
      research in this area is relatively underdeveloped and a better evidence base is
      needed. Worryingly, the waterpipe industry, including waterpipe cafes, operates
      in an almost completely unregulated market and employs deceptive marketing
      techniques to attract new users. CONCLUSIONS: Waterpipe tobacco smoking (WTS)
      appears to be on the increase, especially among younger users, and therefore
      represents a potential public health concern. While legislators should consider
      enforcing and extending existing tobacco laws to a growing WTS industry, further
      research is required to fill gaps in the literature and provide evidence-based
      interventions for tobacco control specialists and health-care professionals.

PMID- 23863045
TI  - Identifying critical unrecognized sugar-protein interactions in GH10 xylanases
      from Geobacillus stearothermophilus using STD NMR.
AB  - (1)H solution NMR spectroscopy is used synergistically with 3D crystallographic
      structures to map experimentally significant hydrophobic interactions upon
      substrate binding in solution under thermodynamic equilibrium. Using saturation
      transfer difference spectroscopy (STD NMR), a comparison is made between wild
      type xylanase XT6 and its acid/base catalytic mutant E159Q--a non-active, single
      heteroatom alteration that has been previously utilized to measure binding
      thermodynamics across a series of xylooligosaccharide-xylanase complexes
      [Zolotnitsky et al. (2004) Proc Natl Acad Sci USA 101, 11275-11280). In this
      study, performing STD NMR of one substrate screens binding interactions to two
      proteins, avoiding many disadvantages inherent to the technique and clearly
      revealing subtle changes in binding induced upon mutation of the catalytic Glu.
      To visualize and compare the binding epitopes of xylobiose-xylanase complexes, a
      'SASSY' plot (saturation difference transfer spectroscopy) is used. Two
      extraordinarily strong, but previously unrecognized, non-covalent interactions
      with H2-5 of xylobiose were observed in the wild-type enzyme but not in the E159Q
      mutant. Based on the crystal structure, these interactions were assigned to
      tryptophan residues at the -1 subsite. The mutant selectively binds only the beta
      xylobiose anomer. The (1)H solution NMR spectrum of a xylotriose-E159Q complex
      displays non-uniform broadening of the NMR signals. Differential broadening
      provides a unique subsite assignment tool based on structural knowledge of face
      to-face stacking with a conserved tyrosine residue at the +1 subsite. The results
      obtained herein by substrate-observed NMR spectroscopy are discussed further in
      terms of methodological contributions and mechanistic understanding of substrate
      binding adjustments upon a charge change in the E159Q construct.

PMID- 23863046
TI  - Fever, hyperthermia and the heat shock response.
AB  - The heat shock response is a highly conserved primitive response that is
      essential for survival against a wide range of stresses, including extremes of
      temperature. Fever is a more recently evolved response, during which organisms
      raise their core body temperature and temporarily subject themselves to thermal
      stress in the face of infections. The present review documents studies showing
      the potential overlap between the febrile response and the heat shock response
      and how both activate the same common transcriptional programme (although with
      different magnitudes) including the stress-activated transcription factor, heat
      shock factor-1, to modify host defences in the context of infection, inflammation
      and injury. The review focuses primarily on how hyperthermia within the febrile
      range that often accompanies infections and inflammation acts as a biological
      response modifier and modifies innate immune responses. The characteristic 2-3 
      degrees C increase in core body temperature during fever activates and utilises
      elements of the heat shock response pathway to modify cytokine and chemokine gene
      expression, cellular signalling and immune cell mobilisation to sites of
      inflammation, infection and injury. Interestingly, typical proinflammatory
      agonists such as Toll-like receptor agonists modify the heat shock-induced
      transcriptional programme and expression of HSP genes following co-exposure to
      febrile range hyperthermia or heat shock, suggesting a complex reciprocal
      regulation between the inflammatory pathway and the heat shock response pathway.

PMID- 23863047
TI  - The use of a CoolSense device to lower pain sensation during finger pricking
      while measuring blood glucose in diabetes patients--a randomized placebo.
AB  - BACKGROUND: Patients with type 1 diabetes and a significant portion of patients
      with type 2 diabetes must use subcutaneous insulin injections, in order to
      maintain normoglycemia and to prevent immediate and long-term complications. For
      these patients, testing blood glucose levels more frequently is necessary to
      safely achieve glycated hemoglobin targets. In the current study, the effects of
      a CoolSenseTM device (CoolSense Medical Ltd., Tel Aviv, Israel) were examined in
      relieving pain caused by needle-pricking for glucose measurements in adult
      patients with diabetes. SUBJECTS AND METHODS: One hundred seventy-seven patients
      assessed the severity of pain they experienced during needle-pricking. The
      patients were randomly divided into an experimental group or a control group that
      used either a cooled CoolSense instrument or a non-cooled device, respectively.
      Participants were asked to rank the severity of their pain by a questionnaire
      developed for this study. Blood glucose levels were monitored as a control.
      RESULTS: The majority of participants (58.3-71.7%; P<0.001) reported significant
      ache during measurements, the desire for an instrument that relieves pain, and
      its negative influence on their quality of life. Significant differences were
      indicated in pain perception between the experimental group and the control group
      that served as placebo, with no differences in blood glucose measurements in the
      groups. CONCLUSIONS: The CoolSense instrument significantly reduces subjective
      pain felt by patients and can therefore serve as an additional tool for
      clinicians to help ease the needle-pricking pain. Future study is needed in order
      to provide information regarding the practical use of the instrument and its
      effect on hyper- and hypoglycemia.

PMID- 23863048
TI  - Tobacco use among homeless people--addressing the neglected addiction.

PMID- 23863049
TI  - Communicating and promoting comparative-effectiveness research findings.

PMID- 23863051
TI  - Targeting of low-dose CT screening according to the risk of lung-cancer death.
AB  - BACKGROUND: In the National Lung Screening Trial (NLST), screening with low-dose
      computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality
      among participants between the ages of 55 and 74 years with a minimum of 30 pack
      years of smoking and no more than 15 years since quitting. It is not known
      whether the benefits and potential harms of such screening vary according to lung
      cancer risk. METHODS: We assessed the variation in efficacy, the number of false
      positive results, and the number of lung-cancer deaths prevented among 26,604
      participants in the NLST who underwent low-dose CT screening, as compared with
      the 26,554 participants who underwent chest radiography, according to the
      quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the
      lowest-risk group [quintile 1] to more than 2.00% in the highest-risk group
      [quintile 5]). RESULTS: The number of lung-cancer deaths per 10,000 person-years
      that were prevented in the CT-screening group, as compared with the radiography
      group, increased according to risk quintile (0.2 in quintile 1, 3.5 in quintile
      2, 5.1 in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for
      trend). Across risk quintiles, there were significant decreasing trends in the
      number of participants with false positive results per screening-prevented lung
      cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in
      quintile 4, and 65 in quintile 5). The 60% of participants at highest risk for
      lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening
      prevented lung-cancer deaths and for 64% of participants with false positive
      results. The 20% of participants at lowest risk (quintile 1) accounted for only
      1% of prevented lung-cancer deaths. CONCLUSIONS: Screening with low-dose CT
      prevented the greatest number of deaths from lung cancer among participants who
      were at highest risk and prevented very few deaths among those at lowest risk.
      These findings provide empirical support for risk-based targeting of smokers for
      such screening. (Funded by the National Cancer Institute.).

PMID- 23863053
TI  - Images in clinical medicine: Congenital melanocytic nevus.

PMID- 23863052
TI  - Clinical practice: Herpes zoster.

PMID- 23863054
TI  - Case Records of the Massachusetts General Hospital: Case 22-2013: A 51-year-old
      woman with epistaxis and oral mucosal ulcers.

PMID- 23863050
TI  - Alpha emitter radium-223 and survival in metastatic prostate cancer.
AB  - BACKGROUND: Radium-223 dichloride (radium-223), an alpha emitter, selectively
      targets bone metastases with alpha particles. We assessed the efficacy and safety
      of radium-223 as compared with placebo, in addition to the best standard of care,
      in men with castration-resistant prostate cancer and bone metastases. METHODS: In
      our phase 3, randomized, double-blind, placebo-controlled study, we randomly
      assigned 921 patients who had received, were not eligible to receive, or declined
      docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of
      50 kBq per kilogram of body weight intravenously) or matching placebo; one
      injection was administered every 4 weeks. In addition, all patients received the
      best standard of care. The primary end point was overall survival. The main
      secondary efficacy end points included time to the first symptomatic skeletal
      event and various biochemical end points. A prespecified interim analysis,
      conducted when 314 deaths had occurred, assessed the effect of radium-223 versus
      placebo on survival. An updated analysis, when 528 deaths had occurred, was
      performed before crossover from placebo to radium-223. RESULTS: At the interim
      analysis, which involved 809 patients, radium-223, as compared with placebo,
      significantly improved overall survival (median, 14.0 months vs. 11.2 months;
      hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided
      P=0.002). The updated analysis involving 921 patients confirmed the radium-223
      survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95%
      CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points
      also showed a benefit of radium-233 as compared with placebo. Radium-223 was
      associated with low myelosuppression rates and fewer adverse events. CONCLUSIONS:
      In this study, which was terminated for efficacy at the prespecified interim
      analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer
      HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

PMID- 23863055
TI  - Fighting prostate cancer with radium-223--not your Madame's isotope.

PMID- 23863056
TI  - Fibrinolysis or primary PCI in myocardial infarction.

PMID- 23863057
TI  - Fibrinolysis or primary PCI in myocardial infarction.

PMID- 23863058
TI  - Fibrinolysis or primary PCI in myocardial infarction.

PMID- 23863059
TI  - Therapy in primary mediastinal B-cell lymphoma.

PMID- 23863060
TI  - Therapy in primary mediastinal B-cell lymphoma.

PMID- 23863061
TI  - Therapy in primary mediastinal B-cell lymphoma.

PMID- 23863062
TI  - Colony-stimulating factors for febrile neutropenia.

PMID- 23863063
TI  - Colony-stimulating factors for febrile neutropenia.

PMID- 23863064
TI  - Colony-stimulating factors for febrile neutropenia.

PMID- 23863065
TI  - Colony-stimulating factors for febrile neutropenia.

PMID- 23863066
TI  - Colony-stimulating factors for febrile neutropenia.

PMID- 23863067
TI  - Achievement of goals in U.S. Diabetes Care, 1999-2010.

PMID- 23863068
TI  - Achievement of goals in U.S. diabetes care, 1999-2010.

PMID- 23863069
TI  - Regulation of drugs for early Alzheimer's disease.

PMID- 23863070
TI  - Regulation of drugs for early Alzheimer's disease.

PMID- 23863071
TI  - Metagenomic analysis of tuberculosis in a mummy.

PMID- 23863072
TI  - Whole-genome sequencing for rapid susceptibility testing of M. tuberculosis.

PMID- 23863073
TI  - Images in clinical medicine: Reversible cerebral vasoconstriction after
      preeclampsia.

PMID- 23863075
TI  - How far did US women travel for abortion services in 2008?
AB  - BACKGROUND: Some women must travel substantial distances in order to access
      abortion services, and this can present a barrier to care. This study assesses
      how far abortion patients traveled to a provider in 2008 and which groups were
      more likely to travel farther. METHODS: We used data from a national sample of
      8,338 abortion patients to estimate how far women traveled to get to the facility
      where they obtained their abortion. Chi-square tests and ordered logistic
      regression were used to assess associations and proportional odds of distance
      traveled according to a number of situational and demographic characteristics.
      RESULTS: In 2008, women traveled a mean distance of 30 miles for abortion care
      services, with a median of 15 miles. Sixty-seven percent of patients traveled
      less than 25 miles, and six percent traveled more than 100 miles. Controlling for
      other factors, women who lived in a state with a 24-hour waiting period, women
      obtaining second trimester abortions, those who crossed state lines, and, in
      particular, rural women were more likely to travel greater distances relative to
      their counterparts. Women of color were less likely to travel long distances
      compared to non-Hispanic white women. CONCLUSIONS: This study serves as a
      baseline as, since 2008, a number of states have introduced restrictive
      legislation that may make it necessary for women to travel even farther and may
      also prevent more vulnerable groups from accessing services altogether.

PMID- 23863074
TI  - Factors associated with clinically significant insomnia among pregnant low-income
      Latinas.
AB  - BACKGROUND: Poor sleep, common during pregnancy, is associated with negative
      health risks. The study aimed to identify predictors of clinically significant
      insomnia among pregnant Latinas. METHODS: A total of 1289 pregnant Latinas
      recruited from obstetric clinics completed the Insomnia Severity Index (ISI) and
      questions about demographics and sleep. RESULTS: Clinically significant insomnia
      (ISI>=10) was present among 17% of participants. Significant correlates of
      clinically significant insomnia were higher scores on the Edinburgh Postnatal
      Depression Scale (EPDS) after removing the sleep item (47% of women with EPDS>=9
      and 9% with EPDS<9), completing measures in English (rather than Spanish: 26%
      versus 13%), and income but not pregnancy week, age, highest education level, or
      marital status. The highest percentage of clinically significant insomnia (59%)
      was experienced by women with EPDS>=9 who completed measures in English. The
      lowest percentage of clinically significant insomnia (6.2%) was experienced by
      women with EPDS<9 who completed measures in Spanish. CONCLUSIONS: In this sample
      of low-income, mostly Spanish-speaking pregnant Latinas, rates of clinically
      significant insomnia appear to be higher than rates among nonpregnant Latinas.
      Rates of clinically significant insomnia are particularly high among Latinas with
      elevated depressive symptom severity, a known risk for insomnia. Acculturation,
      as indicated by completing measures in English, may be another risk specific to
      Latinas, possibly owing to loss of some ethnicity-specific protective factors
      (e.g., social support, strong family ties, and group identity). It will be
      important to directly test this explanation in future research.

PMID- 23863076
TI  - Mechanical control of Renilla luciferase.
AB  - We report experiments where the activity of the enzyme luciferase from Renilla
      reniformis is controlled through a DNA spring attached to the enzyme. In the wake
      of previous work on kinases, these results establish that mechanical stress
      applied through the DNA springs is indeed a general method for the artificial
      control of enzymes, and for the quantitative study of mechano-chemical coupling
      in these molecules. We also show proof of concept of the luciferase construct as
      a sensitive molecular probe, detecting a specific DNA target sequence in an easy,
      one-step, homogeneous assay, as well as SNP detection without melting curve
      analysis. 

PMID- 23863077
TI  - Counselling clients to follow 'the rules' of safe sex and ARV treatment.
AB  - Ideas of 'responsible sexuality' are located at the centre of counselling in
      current antiretroviral treatment (ART) programmes. This paper analyses
      counselling practices in three HIV/AIDS clinics in Uganda on the basis of
      participant observation of counselling sessions and interviews with counsellors.
      The paper illustrates how counsellors concentrate on giving general behavioural
      instructions, while clients tend to demonstrate their compliance to these 'rules'
      rather than sharing their more intimate thoughts. This is especially the case in
      the contested terrain of sexual and reproductive behaviour. To explore this
      phenomenon, the paper analyses a number of dynamics characterising HIV
      counselling in Uganda, including the pressures of the global bio-political
      project to 'save lives' with ART, the counsellors' working conditions in resource
      constrained clinics, the professional authority of counsellors and the clients'
      challenges to following the rules. 

PMID- 23863079
TI  - Interactions between grafted cationic dendrimers and anionic bilayer membranes.
AB  - We use polymer self-consistent field theory to study the physics involved in the
      permeation of charged dendrimer molecules across anionic lipid bilayer membranes.
      We specifically examine the influence of dendrimer shape deformations, neutral
      grafts, and pH conditions on the interactions between dendrimers and membranes.
      Our results indicate that the ability of the dendrimer to undergo conformational
      rearrangements plays a crucial role in influencing the interactions between the
      dendrimer and the membrane. At neutral pH, we observe that dendrimers with
      grafted chains are repelled by the anionic bilayers. However, decreasing the
      solution pH to endosomal conditions results in attractive dendrimer-membrane
      interactions under some parametric conditions. We observe that dendrimer
      insertion into the membrane results in a decreased value in membrane tension at
      which rupture occurs and, furthermore, that the rupture tension decreases with
      the addition of grafts to the dendrimer. Our results suggest that dendrimers
      grafted with neutral polymers can serve as effective pH sensitive delivery
      vectors. 

PMID- 23863078
TI  - Development and in vivo quantitative magnetic resonance imaging of polymer
      micelles targeted to the melanocortin 1 receptor.
AB  - Recent emphasis has focused on the development of rationally designed polymer
      based micelle carriers for drug delivery. The current work tests the hypothesis
      that target specificity can be enhanced by micelles with cancer-specific ligands.
      In particular, we describe the synthesis and characterization of a new gadolinium
      texaphyrin (Gd-Tx) complex encapsulated in an IVECT micellar system, stabilized
      through Fe(III) cross-linking and targeted with multiple copies of a specific
      ligand for the melanocortin 1 receptor (MC1R), which has been evaluated as a cell
      surface marker for melanoma. On the basis of comparative MRI experiments, we have
      been able to demonstrate that these Gd-Tx micelles are able to target MC1R
      expressing xenograft tumors in vitro and in vivo more effectively than various
      control systems, including untargeted or un-cross-linked Gd-Tx micelles. Taken in
      concert, the findings reported herein support the conclusion that appropriately
      designed micelles are able to deliver contrast agent payloads to tumors
      expressing the MC1R. 

PMID- 23863080
TI  - Covalent albumin microparticles as an adjuvant for production of mucosal vaccines
      against hepatitis B.
AB  - Covalently modified albumin (BSA) microparticles were developed for potential use
      as an adjuvant in mucosal vaccines against hepatitis B. To synthesize consistent
      protein particles, a covalent approach was proposed to modify BSA. Our strategy
      was to bond maleic anhydride (MA) molecules to BSA structure by nucleophilic
      reaction for further radical cross-linking/polymerization reaction with N',N'
      dimethylacrylamide (DMAAm). The presence of poly(N',N'-dimethylacrylamide) in the
      protein network enables the microparticles to show well-defined, homogeneous
      forms. Cytotoxicity tests showed that the cytotoxic concentration for 50% of VERO
      cells (CC50) was 216.25 +/- 5.30 MUg mL(-1) in 72 h of incubation. The obtained
      CC50 value is relatively low for an incubation time of 72 h, suggesting an
      acceptable biocompatibility. Assay of total protein showed that the encapsulation
      efficiency of the microparticles with hepatitis B surface antigen (HBsAg) was
      77.7 +/- 0.2%. For the reference sample, which was incubated without HBsAg, the
      quantity of protein was below the limit of detection. 

PMID- 23863081
TI  - Anticonvulsant activity of ethanol extracts of Vetiveria zizanioides roots in
      experimental mice.
AB  - CONTEXT: Vetiveria zizanioides Linn. (Gramineae), an aromatic plant commonly
      known as vetiver, is traditionally used for various ailments. Ethanol and aqueous
      extract of this plant found extensive use in Indian folklore medicine and used in
      treatment of a wide range of disorders including seizure. However, the
      anticonvulsant activity of this plant has not been studied. OBJECTIVE: To
      evaluate anticonvulsant activity of ethanol extract of V. zizanioides (EEVZ) in
      experimental mice. MATERIALS AND METHODS: Anticonvulsant activity of EEVZ was
      determined by maximal electroshock stimulation (MES) and pentylenetetrazole (PTZ)
      in mice for 8 d experimental protocol. The extract at a dose of 100, 200 and 400
      mg/kg body weight was administered once by oral route. RESULTS: LD50 value of
      EEVZ in mice was found at a dose of 600 mg/kg body weight. EEVZ at a dose of 400
      mg/kg significantly (p < 0.001) reduced flexion (l5.98 to 3.73 s), extension
      (13.73 to 0.96 s), clonus (14.07 to 4.93 s), stupor (6.29 to 1.22 s) in the MES
      model. Further, it increases onset of clonic (88.25 to 708.32 s/30 min) and tonic
      (139.52 to 1126.39 s/30 min) in the PTZ model. In the PTZ model, 33% normal
      control and 83% EEVZ (100 mg/kg) animals were alive, while 100% protection was
      achieved in standard drug phenobarbital (20 mg/kg), EEVZ (200 mg/kg) and EEVZ
      (400 mg/kg) animals. DISCUSSION AND CONCLUSION: Findings demonstrate that V.
      zizanioides shows significant anticonvulsant activity in mice.

PMID- 23863082
TI  - High throughput sequencing of the Angiostrongylus cantonensis genome: a parasite
      spreading worldwide.
AB  - Angiostrongylus cantonensis is a parasitic nematode of rodents and a leading
      aetiological agent of eosinophilic meningitis in humans. Definitive diagnosis is
      difficult, often relying on immunodiagnostic methods which utilize crude
      antigens. New immunodiagnostic methods based on recombinant proteins are being
      developed, and ideally these methods would be made available worldwide.
      Identification of diagnostic targets, as well as studies on the biology of the
      parasite, are limited by a lack of molecular information on Angiostrongylus spp.
      available in databases. In this study we present data collected from DNA random
      high-throughput sequencing together with proteomic analyses and a cDNA walking
      methodology to identify and obtain the nucleotide or amino acid sequences of
      unknown immunoreactive proteins. 28 080 putative ORFs were obtained, of which
      3371 had homology to other deposited protein sequences. Using the A. cantonensis
      genomic sequences, 156 putative ORFs, matching peptide sequences obtained from
      previous proteomic studies, were considered novel, with no homology to existing
      sequences. Full-length coding sequences of eight antigenic target proteins were
      obtained. In this study we generated not only the complete nucleotide sequences
      of the antigenic protein targets but also a large amount of genomic data which
      may help facilitate future genomic, proteomic, transcriptomic or metabolomic
      studies on Angiostrongylus.

PMID- 23863083
TI  - Quantification of lipid mediator metabolites in human urine from asthma patients
      by electrospray ionization mass spectrometry: controlling matrix effects.
AB  - Eicosanoids (e.g., prostaglandins and leukotrienes) are inflammatory signaling
      molecules that are metabolized and excreted in urine. The quantification of
      eicosanoid metabolites in human urine has been demonstrated to provide insight
      into the inflammatory and oxidative stress status of the individual. However,
      urine is a complex matrix that can exhibit profound matrix effects for
      quantification via liquid chromatography coupled to mass spectrometry (LC-MS/MS).
      This phenomenon can lead to impairment and biasing of results, because the sample
      background is dependent on the fluid intake and water-salt balance. Herein we
      describe an analytical methodology to address these limitations via the
      normalization of extracted urine volume by the ratio of absorbance at 300 nm to
      an optimized reference material. The platform is composed of 4 LC-MS/MS methods
      that collectively quantify 26 lipid mediators and their metabolites, with on
      column limits of detection between 0.55 and 15 fmol. Prior to optimization,
      internal standards exhibited strong matrix effects with up to 50% loss of signal.
      Notably, the accuracy of exact deuterated structural analogues was found to vary
      based upon the number of incorporated deteurium. The platform was used to analyze
      urine from 16 atopic asthmatics under allergen provocation, showing increases in
      metabolites of prostaglandin D2, cysteinyl leukotrienes, and isoprostanes
      following the challenge. This method presents a functional and reproducible
      approach to addressing urine-specific matrix effects that can be readily
      formatted for quantifying large numbers of samples. 

PMID- 23863084
TI  - Human cap methyltransferase (RNMT) N-terminal non-catalytic domain mediates
      recruitment to transcription initiation sites.
AB  - Gene expression in eukaryotes is dependent on the mRNA methyl cap which mediates
      mRNA processing and translation initiation. Synthesis of the methyl cap initiates
      with the addition of 7-methylguanosine to the initiating nucleotide of RNA pol II
      (polymerase II) transcripts, which occurs predominantly during transcription and
      in mammals is catalysed by RNGTT (RNA guanylyltransferase and 5' phosphatase) and
      RNMT (RNA guanine-7 methyltransferase). RNMT has a methyltransferase domain and
      an N-terminal domain whose function is unclear; it is conserved in mammals, but
      not required for cap methyltransferase activity. In the present study we report
      that the N-terminal domain is necessary and sufficient for RNMT recruitment to
      transcription initiation sites and that recruitment occurs in a DRB (5,6-dichloro
      1-beta-D-ribofuranosylbenzimidazole)-dependent manner. The RNMT-activating
      subunit, RAM (RNMT-activating miniprotein), is also recruited to transcription
      initiation sites via an interaction with RNMT. The RNMT N-terminal domain is
      required for transcript expression, translation and cell proliferation. 

PMID- 23863085
TI  - Effective communication about the use of complementary and integrative medicine
      in cancer care.
AB  - Complementary and integrative medicine (CIM) is becoming an increasingly popular
      and visible component of oncology care. Many patients affected by cancer and
      their family members are looking for informed advice and desire communication
      with their physicians about CIM use. Patients affected by cancer come to discuss
      CIM use with intense emotions and are experiencing an existential crisis that
      cannot be ignored. Effective communication is crucial in establishing trust with
      these patients and their families. Communication is now recognized as a core
      clinical skill in medicine, including cancer care, and is important to the
      delivery of high-quality care. The quality of communication affects patient
      satisfaction, decision-making, patient distress and well-being, compliance, and
      even malpractice litigation. The communication process about CIM use requires a
      very sensitive approach that depends on effective communication skills, such as
      experience in listening, encouraging hope, and ability to convey empathy and
      compassion. This process can be divided into two parts: the "how" and the "what".
      The "how" relates to the change in clinician attitude, the process of gathering
      information, addressing patients' unmet needs and emotions, and dealing with
      uncertainty. The "what" relates to the process of information exchange while
      assisting patients in decisions about CIM use by using reliable information
      sources, leading to informed decision-making.

PMID- 23863086
TI  - A Chinese medicine, Kuan-Sin-Yin decoction, improves liver function in hepatitis
      B virus carriers: a randomized, controlled study.
AB  - OBJECTIVE: To examine the effects of a Chinese medical herb complex formula, Kuan
      Sin-Yin (KSY) decoction, on hepatitis B virus (HBV) carriers. METHODS: Of 86 HBV
      carriers, 57 who met the inclusion criteria completed this study from February
      2011 to December 2011 in Taipei City Hospital, Taiwan. The participants were
      randomly assigned to one of two groups: the KSY group (n=29) and a control group
      (n=28) that received KSY diluted 16 times. The participants took one packet of
      decoction per day after dinner for 6 weeks. The major outcome measurements were
      the percentage reduction in alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), and the log of the HBV DNA level. The other measurements
      included seroconversion of hepatitis B e antigen and responses to the World
      Health Organization Quality of Life-Brief Version (WHOQOL-BREF) and Short-Form
      12. The measurements were collected before the first treatment and 6 weeks later.
      RESULTS: In the KSY group, AST and ALT levels decreased significantly and the
      score on the physical component of WHOQOL-BREF increased significantly. However,
      in the control group, there was no significant change after 6 weeks of treatment.
      Only the KSY group had a significant percentage reduction in ALT (change, -25.2%
      versus -0.74% in the control group) after 6 weeks of treatment. No major adverse
      effects occurred after 6 weeks of treatment. CONCLUSIONS: KSY significantly
      improved ALT levels. The study suggests that a longer-term study testing the
      efficacy of KSY in a larger sample is warranted.

PMID- 23863087
TI  - Self-reported health characteristics and medication consumption by CAM users and
      nonusers: a Swiss cross-sectional survey.
AB  - OBJECTIVES: Complementary and alternative medicine (CAM) is very popular in
      Switzerland. The objective of this work was to find out whether the use of CAM
      therapies is associated with distinct health characteristics and altered
      consumption of conventional medications. DESIGN AND PARTICIPANTS: Self-reported
      data from the 2007 Swiss Health Survey were analyzed. Two groups of participants
      were defined and compared with each other: CAM users (those who had used CAM
      during the last 12 months, n=3333) and nonusers (those who stated they had not
      used CAM during the last 12 months, n=9821). OUTCOME MEASURES: Multivariate
      logistic regression models were used to determine the predictors of CAM use and
      to address relevance and magnitude of the differences in medication consumption
      between CAM users and nonusers. RESULTS: Comparatively lower body-mass index
      (BMI) values and migraine, arthritis, allergies, and depression were associated
      with increased probability of CAM use. Multivariate logistic regression models
      that adjusted for the effects of relevant demographic factors, BMI, and perceived
      health status showed that CAM users consumed fewer medications for cardiovascular
      diseases--high blood pressure and high cholesterol (and, by trend, heart problems
      and diabetes)--than nonusers. On the other hand, their consumption of analgesics
      and medications for depression and for constipation (and, by trend, sedatives and
      soporifics), was higher than that of nonusers. CONCLUSIONS: Migraine, arthritis,
      depression, and constipation might lead patients to use CAM therapies and, in
      addition, to consume more of some conventional medications. Given the long intake
      period and considerable adverse effects of medications, the lower consumption of
      these agents for chronic cardiovascular problems by CAM users might be beneficial
      and deserves further investigations.

PMID- 23863088
TI  - A comparative study of LiCoO2 polymorphs: structural and electrochemical
      characterization of O2-, O3-, and O4-type phases.
AB  - O4-type LiCoO2 as a third polymorph of LiCoO2 is prepared by an ion-exchange
      method in aqueous media from OP4-[Li, Na]CoO2, which has an intergrowth structure
      of O3-LiCoO2 and P2-Na0.7CoO2. O4-type LiCoO2 is characterized by synchrotron X
      ray diffraction, neutron diffraction, and X-ray absorption spectroscopy.
      Structural characterization reveals that O4-type LiCoO2 has an intergrowth
      structure of O3- and O2-LiCoO2 with stacking faulted domains. Three LiCoO2
      polymorphs are formed from the close-packed CoO2 layers, which consist of edge
      shared CoO6 octahedra, whereas the oxide-ion stacking is different: cubic in the
      O3-phase, cubic/hexagonal in the O2-phase, and alternate O3 and O2 in the O4
      phase. Structural analysis using the DIFFaX program suggests that the O4-phase
      consists of approximately 30% of O12-domains, while stacking faults are not
      evidenced for O2-phase. The results suggest that a nucleation process for Na/Li
      ion-exchange kinetically dominates a growth process of ideal O4-domains because
      the presence of CoO2-Li-CoO2 blocks as O3-domains could be expected to prevent
      through-plane interaction of Na layers. Electrochemical behavior and structural
      transition processes for three LiCoO2 polymorphs are compared in Li cells. A new
      phase, OT(#)4-type Li0.5CoO2, is first isolated as an intergrowth phase of O3-
      and T(#)2-Li0.5CoO2. However, some deviations from ideal behavior as the O2/O3
      intergrowth phase are also noted, presumably because of the existence of stacking
      faults. 

PMID- 23863090
TI  - A new class of sky-blue-emitting Ir(III) phosphors assembled using fluorine-free
      pyridyl pyrimidine cyclometalates: application toward high-performance sky-blue-
      and white-emitting OLEDs.
AB  - Two pyrimidine chelates with the pyridin-2-yl group residing at either the 5- or
      4-positions are synthesized. These chelates are then utilized in synthesizing of
      a new class of heteroleptic Ir(III) metal complexes, namely [Ir(b5ppm)2(fppz)]
      (1), [Ir(b5bpm)2(fppz)] (2), [Ir(b4bpm)2(fppz)] (3), and [Ir(b5bpm)(fppz)2] (4),
      for which the abbreviations b5ppm, b5bpm, b4bpm, and fppz represent chelates
      derived from 2-t-butyl-5-(pyridin-2-yl)pyrimidine, 2-t-butyl-5-(4-t-butylpyridin
      2-yl)pyrimidine, 2-t-butyl-4-(4-t-butylpyridin-2-yl)pyrimidine, and 3
      trifluoromethyl-5-(pyridin-2-yl) pyrazole, respectively. The single crystal X-ray
      structural analyses were executed on 1 to reveal their coordination arrangement
      around the Ir(III) metal element. The 5-substituted pyrimidine complexes 1, 2,
      and 4 exhibited the first emission peak wavelength (lambdamax) located in the
      range 452-457 nm with high quantum yields, whereas the emission of 3 with 4
      substituted pyrimidine was red-shifted substantially to longer wavelength with
      lambdamax = 535 nm. These photophysical properties were discussed under the basis
      of computational approaches, particularly the relationship between emission color
      and the relative position of nitrogen atoms of pyrimidine fragment. For
      application, organic light-emitting diodes (OLEDs) were also fabricated using 2
      and 4 as dopants, attaining the peak external quantum, luminance, and power
      efficiencies of 17.9% (38.0 cd/A and 35.8 lm/W) and 15.8% (30.6 cd/A and 24.8
      lm/W), respectively. Combining sky blue-emitting 2 and red-emitting
      [Os(bpftz)2(PPh2Me)2] (5), the phosphorescent white OLEDs were demonstrated with
      stable pure-white emission at CIE coordinate of (0.33, 0.34), and peak luminance
      efficiency of 35.3 cd/A, power efficiency of 30.4 lm/W, and external quantum
      efficiency up to 17.3%. 

PMID- 23863089
TI  - Quality and accuracy of Internet information concerning a healthy diet.
AB  - The Internet is used by many consumers interested in healthy living. The aim of
      the present study was to explore the variations among Internet information
      concerning a healthy diet and to evaluate the potential for misleading
      information. To conduct a descriptive analysis, the search term "healthy diet"
      was entered into three search engines and the first 100 results were examined. Of
      the evaluated 48 websites, 5, 26 and 11, respectively, gave references, date when
      information was updated and cautioned users. For assessment of accuracy, six
      dietary guidelines were used as references and the website was scored according
      to the number of recommended dietary features that matched the guidelines.
      Websites that specified their objectives scored significantly higher when matched
      with each guideline than the websites that did not state four guidelines (p <
      0.05). Internet information on a "healthy diet" was likely to only partially
      follow recommendations of the guidelines.

PMID- 23863091
TI  - Functional results after orthotopic bladder substitution: a prospective
      multicentre study comparing four types of neobladder.
AB  - OBJECTIVE: The aim of this study was to evaluate enterocystometry, voiding
      pattern and urine leakage of four types of orthotopic bladder substitute.
      MATERIAL AND METHODS: At eight urological departments, 78 consecutive men were
      studied: 66 with an ileal neobladder [30 Studer pouches (S), 24 Hautmann pouches
      (H) and 12 T-pouches (T)] and 12 with a right colonic [Goldwasser type (G)]
      neobladder. Enterocystometry, determination of residual urine, micturition
      protocol and 24 h pad weight test were performed 6 and 12 months postoperatively.
      RESULTS: Colonic neobladders had higher pouch pressure at first desire, normal
      desire and strong desire than ileal neobladders (except at first and normal
      desire at 12 months) (p < 0.02) and contraction was present more often at both 6
      and 12 months (p < 0.01 and p < 0.01). Compliance was good in all types of pouch.
      Intermittent self-catheterization was more common in H patients at 6 months (p =
      0.033). All patients with colonic neobladders used pads during the day and night.
      In patients with ileal pouches 32% used pads during the day and 70% during the
      night at 12 months. Urine leakage was higher in patients with colonic bladders at
      6 and 12 months during the day (mean/median of 98/31 ml and 82/16 ml versus 10/0
      ml and 4/0 ml, p < 0.001). T-pouches had excellent day-time continence, but
      nocturnal leakage was high. CONCLUSIONS: The Hautmann pouch and the Studer pouch
      behaved similarly at enterocystometry and clinically, and continence was good in
      the majority of patients. The low number of patients with the other two types of
      pouch precludes definitive statements.

PMID- 23863092
TI  - Does lowering evening rectal temperature to morning levels offset the diurnal
      variation in muscle force production?
AB  - Muscle force production and power output in active males, regardless of the site
      of measurement (hand, leg, or back), are higher in the evening than the morning.
      This diurnal variation is attributed to motivational, peripheral, and central
      factors and higher core and, possibly, muscle temperatures in the evening. This
      study investigated whether decreasing evening resting rectal temperatures to
      morning values, by immersion in a water tank, leads to muscle force production
      and power output becoming equal to morning values in motivated subjects. Ten
      healthy active males (mean +/- SD: age, 22.5 +/- 1.3 yrs; body mass, 80.1 +/- 7.8
      kg; height, 1.72 +/- 0.05 m) completed the study, which was approved by the local
      ethics committee of the university. The subjects were familiarized with the
      techniques and protocol and then completed three sessions (separated by at least
      48 h): control morning (07:30 h) and evening (17:30 h) sessions (with an active 5
      min warm-up on a cycle ergometer at 150 W) and then a further session at 17:30 h
      but preceded by an immersion in cold water (~16.5  degrees C) to lower rectal
      temperature (Trec) to morning values. During each trial, three measures of grip
      strength, isokinetic leg strength measurements (of knee flexion and extension at
      1.05 and 4.19 rad s(-1) through a 90 degrees  range of motion), and three
      measures of maximal voluntary contraction (MVC) on an isometric dynamometer
      (utilizing the twitch-interpolation technique) were performed. Trec, rating of
      perceived exertion (RPE), and thermal comfort (TC) were also measured after the
      subjects had reclined for 30 min at the start of the protocol and prior to the
      measures for grip, isokinetic, and isometric dynamometry. Muscle temperature was
      taken after the warm-up or water immersion and immediately before the isokinetic
      and MVC measurements. Data were analyzed using general linear models with
      repeated measures. Trec values were higher at rest in the evening (by 0.37 
      degrees C; p < 0.05) than the morning, but values were no different from morning
      values immediately after the passive pre-cooling. However, Trec progressively
      decreased throughout the experiments, this being reflected in the subjects'
      ratings of thermal comfort. Muscle temperatures also displayed significant
      diurnal variation, with higher values in the evening (by 0.39  degrees C; p <
      0.05). Right grip strength, isometric peak power, isokinetic knee flexion and
      extension for peak torque and peak power at 1.05 rad s(-1), and knee extension
      for peak torque at 4.19 rad s(-1) all showed higher values in the evening (a
      range of 3-14%), and all other measures of strength or power showed a statistical
      trend to be higher in the evening (0.10 > p > 0.05). Pre-cooling in the evening
      significantly reduced force or power variables towards morning values. In
      summary, effects of time of day were seen in some measures of muscle performance,
      in agreement with past research. However, in this population of motivated
      subjects, there was evidence that decreasing evening Trec to morning values by
      coldwater immersion decreased muscle strength to values similar to those found in
      the morning. It is concluded that diurnal changes in muscle performance are
      linked to diurnal changes in Trec.

PMID- 23863093
TI  - Enhanced surfactant supramicellar assembly by hydrophobic dopants.
AB  - The light scattering peak (LS peak) near the surfactant critical micelle
      concentration (cmc) demonstrates that low hydrophobic dopant levels can cause
      supramolecular assembly of surfactants into metastable structures much more
      massive than dopant-free micelles. These supramicellar assemblies (SA) exist over
      the entire LS peak region, which extends from above the cmc down to well below
      the cmc. Dodecanol (D) was the dopant, and sodium dodecyl sulfate (SDS) and
      dodecyl trimethyl ammonium bromide (DTABr) were the surfactants in this work.
      Well above the cmc dopant is solubilized by micelles. The SA appear above the
      cmc, dependent on dopant level and solution ionic strength, as seen by an abrupt
      increase in LS. Hence, the micelles do not simply release their hydrophobic
      payload at the cmc; rather, the dopant causes a morphological change from normal
      micelles above the LS peak concentration regime into SA as the LS regime is
      entered from above the cmc. Below the cmc the LS peak has a cutoff concentration
      corresponding to the solubility limit of dodecanol in water, which can be termed
      a "critical supramicellar assembly concentration" (csac). A three-component model
      is proposed that self-consistently yields maximum micellar dopant loading, SA
      mass, and dopant solubility in solution. The constancy of SA molar mass under
      widely different ionic strength and dopant levels conditions is surprising and
      not currently understood. 

PMID- 23863094
TI  - Heat shock proteins can be targets of regulatory T cells for therapeutic
      intervention in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by
      excessive immune responses resulting in inflammation of the joints. Although
      current therapies can be successful in dampening inflammation, a long-lived state
      of tolerance is seldom achieved. Therefore, novel therapies are needed that
      restore and maintain tolerance in patients with RA. Targeting regulatory T cells
      (Tregs) is a successful strategy to achieve tolerance, as was shown in studies
      performed in animal models and in human clinical trials. The antigen-specificity
      of Tregs is crucial for their effectiveness and allows for very specific
      targeting of these cells. However, which antigen is suitable for autoimmune
      diseases such as RA, for which the autoantigens are largely unknown? Heat shock
      proteins (HSPs) are ubiquitously expressed and can be up-regulated during
      inflammation. Additionally, HSPs, or HSP-derived peptides are immunogenic and can
      be recognised by a variety of immune cells, including Tregs. Therefore, this
      review highlights the potential of HSP-specific Tregs to control inflammatory
      immune responses. Targeting HSP-specific Tregs in RA can be achieved via the
      administration of HSPs (derived peptides), thereby controlling inflammatory
      responses. This makes HSPs attractive candidates for therapeutic intervention in
      chronic autoimmune diseases, with the ultimate goal of inducing long-lasting
      tolerance.

PMID- 23863095
TI  - Capillary osmosis in a charged nanopore connecting two large reservoirs.
AB  - Experimental evidence revealed that the performance of nanopore-based biosensing
      devices can be improved by applying a salt concentration gradient. To provide a
      theoretical explanation for this observation and explore the mechanisms involved,
      we model the capillary osmosis (or diffusioosmosis) in a charged solid-state
      nanopore connecting two large reservoirs. The effects of nanopore geometry and
      the reservoir salt concentrations are examined. We show that the capillary
      osmotic flow is from the high salt concentration reservoir to the low salt
      concentration one, and its magnitude has a maximum as the reservoir salt
      concentrations vary. In general, the shorter the nanopore and/or the smaller its
      radius, the faster the osmotic flow. This flow enhances the current recognition,
      and the ion concentration polarization across nanopore openings raises the entity
      capture rate, thereby being capable of improving the performance of
      electrophoresis-based biosensors. The results gathered provide necessary
      information for designing nanopore-based biosensor devices. 

PMID- 23863096
TI  - L1-ORF1p, a Smad4 interaction protein, promotes proliferation of HepG2 cells and
      tumorigenesis in mice.
AB  - Long interspersed nucleotide element (LINE-1; L1) as an autonomous
      retrotransposon is localized usually in AT-rich, low-recombined, and gene-poor
      regions of genome. It is transiently activated in embryonic development and
      continuously activated in all tumor cells tested so far. Full-length L1 gene
      contains 5' untranslated region, two open reading frames (ORFs) encoded L1ORF1p
      and L1ORF2p, and a 3' terminal polyadenylation site. Compared with L1ORF2p, a
      protein encompassing reverse transcriptase and endonuclease activities, L1ORF1p
      remains to be elucidated. With liver cancer cells and tissues, the expression and
      sub-localization of L1ORF1p were investigated and shown that L1-ORF1p expresses
      just in liver cancer cells and tissues but not in normal liver cells and almost
      not in adjacent tissues. To characterize L1ORF1p, the strategies for over
      expression and down-regulation of L1ORF1p in transfected cells were implemented.
      The phenomenon of promoting cell proliferation and colony formation was observed
      in transfected cells with L1ORF1p over-expression and vice versa. Down-regulation
      of L1ORF1p suppresses tumorigenesis in vitro and in vivo. Smad4 as an interaction
      protein of L1ORF1p is identified for the first time, while L1ORF1p is responsible
      for Smad4 sequestration in the cytoplasm. Thus, L1ORF1p contributed to
      tumorigenesis and may attribute to, at least partly, its participation in Smad4
      signaling regulation. 

PMID- 23863097
TI  - Discovery of novel candidate therapeutics and diagnostics based on engineered
      human antibody domains.
AB  - The smallest independently folded antibody fragments, the domains, are emerging
      as promising scaffolds for candidate therapeutics and diagnostics that bind
      specifically targets of interest. The discovery of such binders is based on
      several technologies including structure-based design and generation of libraries
      of mutants displayed on phage or yeast, next-generation sequencing for diversity
      analysis, panning and screening of the libraries, affinity maturation of selected
      binders, and their expression, purification, and characterization for specific
      binding, function, and aggregation propensity. In this review, we describe these
      technologies as applied for the generation of engineered antibody domains (eAds),
      especially those derived from the human immunoglobulin heavy chain variable
      region (VH) and the second domain of IgG1 heavy chain constant region (CH2) as
      potential candidate therapeutics and diagnostics, and discuss examples of eAds
      against HIV-1 and cancer-related proteins. 

PMID- 23863098
TI  - Formulation and evaluation of niosomal nasal drug delivery system of folic acid
      for brain targeting.
AB  - Nasal mucosa offers advantages to deliver drugs to brain via olfactory route thus
      provides rapid onset of drug action and hence faster therapeutic effect.
      Therefore, various strategies have been proposed to improve the delivery of
      different drugs to brain including liposomes, colloidal drug carriers, micelles,
      chimeric peptide technology and nanotechnology through nasal route. The low blood
      level of folates is the primary cause of depression in Alzheimer's disease. Folic
      acid is a water soluble vitamin showing difficulty in crossing the blood brain
      barrier and thus was formulated as niosomal nasal drug delivery systems to target
      the brain. In the present work, folic acid niosomes were prepared using different
      nonionic surfactants i.e., span 20, span 60, span 80, tween 20, tween 80 and
      cholesterol by using lipid layer hydration technique. These were evaluated for
      particle size, viscosity, osmotic shock, entrapment efficiency and in vitro drug
      release. The influence of different formulation variables such as surfactant
      type, surfactant concentration, and cholesterol concentration was optimized for
      required size distribution, viscosity, entrapment efficiency and in vitro
      release. The prepared niosomes were in the size range of 3.05-5.625 um. Niosomes
      prepared with span 60 and cholesterol in the ratio of 1:1 (50 mg: 50 mg) shown
      higher entrapment efficiency of 69.42% and better in vitro drug release of 64.2%
      at the end of 12 hrs and therefore considered as optimized formulation. The
      stability studies were carried out by storing niosomes at 4+/-1 degrees C and
      25+/-1 degrees C and showed good stability over the period of storage. The
      release of drug from niosomes followed anomalous diffusion and obeyed first order
      release kinetics. Ex-vivo perfusion studies were also performed by using rat
      model, about 48.15% of drug was found to be absorbed through nasal cavity at the
      end of 6 hrs.

PMID- 23863099
TI  - Endoscopic primary dacryocystorhinostomy: are silicone tubes needed? Our
      experience in sixty three patients.

PMID- 23863100
TI  - Training of goal directed arm movements with motion interactive video games in
      children with cerebral palsy - a kinematic evaluation.
AB  - OBJECTIVE: The main aim of this study was to evaluate the quality of goal
      directed arm movements in 15 children with cerebral palsy (CP) following four
      weeks of home-based training with motion interactive video games. A further aim
      was to investigate the applicability and characteristics of kinematic parameters
      in a virtual context in comparison to a physical context. METHOD: Kinematics and
      kinetics were captured while the children performed arm movements directed
      towards both virtual and physical targets. RESULTS: The children's movement
      precision improved, their centre of pressure paths decreased, as did the
      variability in maximal shoulder angles when reaching for virtual objects.
      Transfer to a situation with physical targets was mainly indicated by increased
      movement smoothness. CONCLUSION: Training with motion interactive games seems to
      improve arm motor control in children with CP. The results highlight the
      importance of considering both the context and the task itself when investigating
      kinematic parameters.

PMID- 23863101
TI  - Predicting morphologies of solution processed polymer:fullerene blends.
AB  - The performance of solution processed polymer:fullerene thin film photovoltaic
      cells is largely determined by the nanoscopic and mesoscopic morphology of these
      blends that is formed during the drying of the layer. Although blend morphologies
      have been studied in detail using a variety of microscopic, spectroscopic, and
      scattering techniques and a large degree of control has been obtained, the
      current understanding of the processes involved is limited. Hence, predicting the
      optimized processing conditions and the corresponding device performance remains
      a challenge. We present an experimental and modeling study on blends of a small
      band gap diketopyrrolopyrrole-quinquethiophene alternating copolymer (PDPP5T) and
      [6,6]-phenyl-C71-butyric acid methyl ester ([70]PCBM) cast from chloroform
      solution. The model uses the homogeneous Flory-Huggins free energy of the
      multicomponent blend and accounts for interfacial interactions between (locally)
      separated phases, based on physical properties of the polymer, fullerene, and
      solvent. We show that the spinodal liquid-liquid demixing that occurs during
      drying is responsible for the observed morphologies. The model predicts an
      increasing feature size and decreasing fullerene concentration in the polymer
      matrix with increasing drying time in accordance with experimental observations
      and device performance. The results represent a first step toward a predictive
      model for morphology formation. 

PMID- 23863102
TI  - When 'raw sex' turns to a 'raw deal' ... taking the opportunity to think about
      sex? Interviews with HIV-positive gay men diagnosed with acute hepatitis C.
AB  - Since 2001, cases of hepatitis C virus (HCV) sexual transmission have been
      reported in France, among HIV-positive gay men who do not inject drugs. An
      earlier study focused on the incidence of acute hepatitis C and risk factors
      associated with HCV transmission. The present study, based on in-depth
      interviews, aimed to highlight the biography, the sexual practices and the
      experiences of gay men infected with HCV. Beyond an apparent uniformity, the
      group of interviewees illustrates a variety of situations, life stories and
      health pathways, depending on their age. These well-adjusted gay men were used to
      engaging in unprotected sexual practices, but before their diagnosis they largely
      ignored HCV-transmission risk, which was associated in their mind with a
      pejorative drug addict image. Once diagnosed with acute hepatitis C, they
      experienced a critical and emotional period during which they were open to
      discuss their sexual practices and reconsider risk-reduction procedures, without
      being willing to give up on their satisfying sex life. Health educators should
      consider labelling hepatitis C as an STI in order to disrupt its negative image
      and to help HIV-positive gay man raise their awareness of HCV-transmission risks
      and implement better risk-reduction strategies.

PMID- 23863103
TI  - Protein adsorption at nanopatterned surfaces studied by quartz crystal
      microbalance with dissipation and surface plasmon resonance.
AB  - This paper presents the use of the quartz crystal microbalance with dissipation
      (QCM-D) combined with surface plasmon resonance (SPR) to probe protein adsorption
      at nanopatterned surfaces. Three different types of adsorbing materials,
      representing rigid discrete nanoparticles, dense protein films, and soft low
      density films have been studied on systematic varied circular nanostructures in
      the 100-1000 nm size range. Analysis and quantification of the QCM-D response
      from larger nanostructures could be understood and quantified in the same way as
      for homogeneous surfaces, while that for nanostructures of 100 and 200 nm
      diameter was significantly underestimated. Our findings suggest a size limitation
      of those techniques in analysis of adsorption at nanofeatures. 

PMID- 23863105
TI  - Diffusion tensor tractography for the dorsal spinocerebellar tract in the human
      brain.
AB  - Using diffusion tensor tractography, we attempted to investigate and identify the
      anatomy of the dorsal spinocerebellar tract (SCT) in the human brain. We
      recruited 26 healthy volunteers. The dorsal SCT was determined by selection of
      fibers passing through three regions of interest. We found that all dorsal SCTs
      terminated in the ipsilateral cerebellum; in contrast, in 25 (48%) of 52
      hemispheres, the dorsal SCT crossed into the contralateral hemisphere via the
      vermis of the anterior lobe.

PMID- 23863104
TI  - Comparison of the antibacterial effect and smear layer removal using photon
      initiated photoacoustic streaming aided irrigation versus a conventional
      irrigation in single-rooted canals: an in vitro study.
AB  - OBJECTIVE: The Er:YAG laser with photon-induced photoacoustic streaming (PIPS)
      technique was reported to be effective in root canal disinfection. This study
      attempted to further investigate the antibacterial efficacy and smear layer
      removal ability of PIPS in comparison with conventional syringe irrigation in
      vitro. METHODS: For antibacterial analysis, 48 single-rooted human teeth were
      prepared and inoculated with Enterococcus faecalis, and then divided into six
      groups of eight roots each. The colony-forming units (CFUs) per milliliter were
      determined after infection as the baseline. Then, the teeth were subjected to
      either PIPS plus 3% sodium hypochlorite (PIPS+NaOCl) or conventional syringe
      irrigation with 0.9% saline, 3% NaOCl, 17% ethylenediaminetetraacetic acid
      (EDTA), 0.2% chlorhexidine gluconate (CHX), or 3% NaOCl alternating with 17%
      EDTA. The reduction of CFUs in the individual group was determined. Additionally,
      scanning electron microscopy (SEM) examination of the canal walls for E. faecalis
      colonization was performed. For comparing the smear removal efficacy, another 48
      single-rooted teeth, assigned to different groups as mentioned, were irrigated
      after mechanical instrumentation. The presence of a smear layer at different
      levels of the root canal was scored by SEM examination. RESULTS: No significant
      differences were found in CFU reduction. No bacteria could be observed by SEM in
      the NaOCl, NaOCl+EDTA, and PIPS+NaOCl groups. The scores of smear layer of the
      NaOCl+EDTA and PIPS+NaOCl groups were significantly lower than those of the other
      groups in the coronal and middle third of the root canal. None of the methods can
      effectively remove smear layer in the apical third. CONCLUSIONS: PIPS system
      supplied with NaOCl and conventional syringe irrigation with NaOCl+EDTA are
      comparable in their ability to remove E. faecalis and smear layer in single
      rooted canals.

PMID- 23863106
TI  - Characterization of the complex formed between a potent neutralizing ovine
      derived polyclonal anti-TNFalpha Fab fragment and human TNFalpha.
AB  - TNFalpha (tumour necrosis factor alpha) is an early mediator in the systemic
      inflammatory response to infection and is therefore a therapeutic target in
      sepsis. AZD9773 is an ovine-derived, polyclonal anti-TNFalpha Fab fragment
      derived from a pool of serum and currently being developed as a treatment for
      severe sepsis and septic shock. In the present study, we show that although
      AZD9773 has a modest affinity for TNFalpha in a binding assay, the Ki in a cell
      based assay is approximately four orders of magnitude lower. We show using SEC
      (size exclusion chromatography) that the maximum size of the complex between
      AZD9773 and TNFalpha is consistent with approximately 12 Fabs binding to one
      TNFalpha trimer. A number of approaches were taken to map the epitopes recognized
      by AZD9773. These revealed that a number of different regions on TNFalpha are
      involved in binding to the polyclonal Fab. The data suggest that there are
      probably three epitopes per monomer that are responsible for most of the
      inhibition by AZD9773 and that all three can be occupied at the same time in the
      complex. We conclude that AZD9773 is clearly demonstrated to bind to multiple
      epitopes on TNFalpha and suggest that the polyclonal nature may account, at least
      in part, for the very high potency observed in cell-based assays. 

PMID- 23863107
TI  - Attaching DNA to nanoceria: regulating oxidase activity and fluorescence
      quenching.
AB  - Cerium oxide nanoparticles (nanoceria) have recently emerged as a nanozyme with
      oxidase activity. In this work, we present a few important interfacial properties
      of nanoceria. First, the surface charge of nanoceria can be controlled not only
      by adjusting pH but also by adsorption of simple inorganic anions. Adsorption of
      phosphate and citrate gives negatively charged surface over a broad pH range.
      Second, nanoceria adsorbs DNA via the DNA phosphate backbone in a sequence
      independent manner; DNA adsorption inhibits its oxidase activity. Other anionic
      polymers display much weaker inhibition effects. Adsorption of simple inorganic
      phosphate does not have the inhibition effect. Third, nanoceria is a quencher for
      many fluorophores. These discoveries provide an important understanding for
      further use of nanoceria in biosensor development, materials science, and
      nanotechnology. 

PMID- 23863108
TI  - Monoclinic Ag2Mo2O7 nanowire: a new Ag-Mo-O nanophotocatalyst material.
AB  - We report a template-free facile technique that allows for the first ever
      synthesis of a monoclinic Ag2Mo2O7 nanowire (m-Ag2Mo2O7-NW), using a commercially
      available MoO3 particle. The nanowire possessed high crystallinity and structural
      homogeneity and strongly suggested that the nanowire was grown through an
      oriented aggregation mechanism in contrast to the case of a typical solution
      phase method. The corresponding bulky counterpart showed no photoresponse;
      however, a complete structural transformation toward a nanowire triggered
      activity for O2 evolution in the presence of Ag(+) as an electron acceptor under
      visible-light irradiation. 

PMID- 23863109
TI  - Stability and viscoelasticity of magneto-Pickering foams.
AB  - We have developed a new class of bistable Pickering foams, which can remain
      intact for weeks at room temperature but can be destroyed rapidly and on-demand
      with the use of a magnetic field. Such responsive foam systems can find
      application in various industrial and environmental processes that require
      controlled defoaming. These foams are stabilized by particles of hypromellose
      phthalate (HP-55) and contain oleic acid-coated carbonyl iron particles embedded
      in the HP-55 matrix. The complex behavior of these foams arises from several
      factors: a robust anisotropic particle matrix, the capacity to retain a high
      amount of water, as well as an age-dependent response to an external field. We
      report how the structure and viscoelastic properties of the foams change with
      time and affect their collapse characteristics. The evolution of foam properties
      is quantified by measuring the rate of liquid drainage from the foam as well as
      the rate of bubble growth in the foam with respect to time elapsed (in the
      absence of a magnetic field). We also evaluate the time necessary for foam
      collapse in magnetic fields as a function of magnetic particle content. A
      decreasing liquid volume fraction in the foam during aging leads to an increase
      in the elasticity and rigidity of the foam structure. These data allow us to
      identify a transition time separating two distinct stages of foam development in
      the absence of field. We propose different mechanisms which control foam collapse
      for each stage in a magnetic field. The stiffening of foam films between air
      bubbles with age plays a key role in distinguishing between the two
      destabilization regimes. 

PMID- 23863110
TI  - Etoposide catechol is an oxidizable topoisomerase II poison.
AB  - Topoisomerase II regulates DNA topology by generating transient double-stranded
      breaks. The anticancer drug etoposide targets topoisomerase II and is associated
      with the formation of secondary leukemias in patients. The quinone and catechol
      metabolites of etoposide may contribute to strand breaks that trigger leukemic
      translocations. To further analyze the characteristics of etoposide metabolites,
      we extend our previous analysis of etoposide quinone to the catechol. We
      demonstrate that the catechol is ~2-3-fold more potent than etoposide and under
      oxidative reaction conditions induces high levels of double-stranded DNA
      cleavage. These results support a role for etoposide catechol in contributing to
      therapy-induced DNA damage. 

PMID- 23863111
TI  - Antimalarial drug discovery - the path towards eradication.
AB  - Malaria is a disease that still affects a significant proportion of the global
      human population. Whilst advances have been made in lowering the numbers of cases
      and deaths, it is clear that a strategy based solely on disease control year on
      year, without reducing transmission and ultimately eradicating the parasite, is
      unsustainable. This article highlights the current mainstay treatments alongside
      a selection of emerging new clinical molecules from the portfolio of Medicines
      for Malaria Venture (MMV) and our partners. In each case, the key highlights from
      each research phase are described to demonstrate how these new potential
      medicines were discovered. Given the increased focus of the community on
      eradicating the disease, the strategy for next generation combination medicines
      that will provide such potential is explained.

PMID- 23863112
TI  - Bioreactivity of the crystalline silica polymorphs, quartz and cristobalite, and
      implications for occupational exposure limits (OELs).
AB  - Silica or silicon dioxides (SiO2) are naturally occurring substances that
      comprise the vast majority of the earth's crust. Because of their prevalence and
      commercial applications, they have been widely studied for their potential to
      induce pulmonary fibrosis and other disorders. Historically, the focus in the
      workplace has been on the development of inflammation and fibrotic lung disease,
      the basis for promulgating workplace standards to protect workers. Crystalline
      silica (CS) polymorphs, predominantly quartz and cristobalite, are used in
      industry but are different in their mineralogy, chemistry, surface features, size
      dimensions and association with other elements naturally and during industrial
      applications. Epidemiologic, clinical and experimental studies in the literature
      historically have predominantly focused on quartz polymorphs. Thus, in this
      review, we summarize past scientific evaluations and recent peer-reviewed
      literature with an emphasis on cristobalite, in an attempt to determine whether
      quartz and cristobalite polymorphs differ in their health effects, toxicity and
      other properties that may dictate the need for various standards of protection in
      the workplace. In addition to current epidemiological and clinical reports, we
      review in vivo studies in rodents as well as cell culture studies that shed light
      on mechanisms intrinsic to the toxicity, altered cell responses and protective or
      defense mechanisms in response to these minerals. The medical and scientific
      literature indicates that the mechanisms of injury and potential causation of
      inflammation and fibrotic lung disease are similar for quartz and cristobalite.
      Our analysis of these data suggests similar occupational exposure limits (OELs)
      for these minerals in the workplace.

PMID- 23863113
TI  - Structure of sphingomyelin bilayers and complexes with cholesterol forming
      membrane rafts.
AB  - Sphingomyelin and cholesterol are of interest to biologists because they interact
      to form condensed structures said to be responsible for a variety of functions
      that membranes perform. Synchrotron X-ray diffraction methods have been used to
      investigate the structure of bilayers of D-erythro palmitoyl-sphingomyelin and
      complexes formed by palmitoyl- and egg-sphingomyelin with cholesterol in aqueous
      multibilayer dispersions. D-erythro palmitoyl sphingomyelin bilayers exist in two
      conformers that are distinguished by their lamellar repeat spacing, bilayer
      thickness, and polar group hydration. The distinction is attributed to hydrogen
      bonding to water or to intermolecular hydrogen bonds that are disrupted by the
      formation of ripple structure. The coexisting bilayer structures of pure
      palmitoyl sphingomyelin are observed in the presence of cholesterol-rich bilayers
      that are characterized by different bilayer parameters. The presence of
      cholesterol preferentially affects the conformer of D-erythro sphingomyelin with
      thicker, more hydrated bilayers. Coexisting bilayers of sphingomyelin and
      complexes with cholesterol are in register and remain coupled at temperatures at
      least up to 50  degrees C. Cholesterol forms a complex of 1.8 mols of
      sphingomyelin per cholesterol at 37  degrees C that coexists with bilayers of
      pure sphingomyelin up to 50  degrees C. Redistribution of the two lipids takes
      place on cooling below the fluid- to gel-phase transition temperature, resulting
      in the withdrawal of sphingomyelin into gel phase and the formation of coexisting
      bilayers of equimolar proportions of the two lipids. Cholesterol-rich bilayers
      fit a stripe model at temperatures less than 37  degrees C characterized by
      alternating rows of sphingomyelin and cholesterol molecules. A quasicrystalline
      array models the arrangement at higher temperatures in which each cholesterol
      molecule is surrounded by seven hydrocarbon chains, each of which is in contact
      with two cholesterol molecules. The thickness of bilayer complexes of
      sphingomyelin and cholesterol is less than that of coexisting bilayers of pure
      sphingomyelin. The implications for protein sorting theories based on bilayer
      thickness are discussed.

PMID- 23863114
TI  - Engineering multicellular logic in bacteria with metabolic wires.
AB  - Aromatic biodegradation pathways of environmental bacteria are vast sources of
      matching trios of enzymes, substrates and regulators that can be refactored to
      run logic operations through cell-to-cell communication. As a proof of concept,
      the connection between two Pseudomonas putida strains using benzoic acid as the
      wiring molecule is presented. In this system, a sender strain harboring the TOL
      pathway for biodegradation of aromatics processed toluene as input and generated
      benzoate as the output signal. Diffusion of such metabolic intermediate to the
      medium was then sensed by a second strain (the receiver) that used benzoate as
      input for a new logic gate producing a visual output (i.e., light emission). The
      setup was functional irrespective of whether sender and receiver cells were in
      direct contact or in liquid culture. These results highlight the potential of
      environmental metabolic pathways as sources of building blocks for the
      engineering of multicellular logic in prokaryotic systems.

PMID- 23863115
TI  - Molecular dynamics simulation study and molecular docking descriptors in
      structure-based QSAR on acetylcholinesterase (AChE) inhibitors.
AB  - In this study we present an approach for predicting the inhibitory activity of
      acetylcholinesterase (AChE) inhibitors by combining molecular dynamics (MD)
      simulation and docking studies in a structure-based quantitative structure
      activity relationship (QSAR) model. The MD simulation was performed on AChE to
      obtain enzyme conformation in a water environment. The resulting conformation of
      the enzyme was used for docking with the most potent inhibitor (26a). Docking
      analysis revealed that hydrophobic interactions play important roles in the AChE
      inhibitor complex. Then, all inhibitors that could bind simultaneously at the
      catalytic site and at the peripheral anionic site of AChE were docked into the
      enzyme and their interactions with AChE were used as new interpretable
      descriptors in a structure-based QSAR model. The least squares support vector
      regression was constructed using the four most relevant docking descriptors and
      one molecular structure descriptor. The Q(2) value of the model was found to be
      0.790. Furthermore, to study the enzyme conformation stability, a second MD
      simulation was performed on AChE-inhibitor 26a complex. In MD simulation, the
      topological parameters of the inhibitor were derived from the PRODRG server, and
      partial atomic charges were modified using the B3LYP/6-31G level of theory. The
      radius of gyration for the complex showed that AChE conformation did not change
      in the presence of the inhibitors.

PMID- 23863116
TI  - Educational outcome in adolescence following pyloric stenosis repair before 3
      months of age: a nationwide cohort study.
AB  - BACKGROUND: Immature animals exposed to anesthetics display apoptotic
      neurodegeneration with subsequent long-term cognitive dysfunctions. Young age at
      anesthetic exposure is believed to be critical, but human studies are scarce.
      This study investigated the association between exposure to surgery and
      anesthesia for pyloric stenosis (PS) before 3 months of age and subsequent
      educational outcome in adolescence. METHODS: This nationwide unselected register
      based follow-up study of the Danish birth cohorts 1986-1990 compared the
      educational outcome of all children having undergone surgery for PS before 3
      months of age with a randomly selected, age-matched 5% sample of the same cohort.
      Primary analysis compared the average test scores at ninth grade adjusting for
      gender, birth weight, and parental age and education. Secondary analysis compared
      the proportions not attaining the test scores between the two groups. RESULTS:
      The exposure group comprised 779 and the control group consisted of 14 665
      individuals. Although the exposure group performed lower than the control group
      (average score 0.17 lower, 95% CI: 0.08-0.25), after adjusting for known
      confounders, no statistically significant difference (-0.04, 95% CI: -0.09 to
      0.08) between the 2 groups could be demonstrated. However, we found an odds ratio
      (OR) for test score nonattainment-associated PS repair of 1.37 (95% CI: 1.11
      1.68). CONCLUSION: Children operated for PS before 3 months of age have
      educational performance tests similar to the background population at age 15-16
      years after adjusting for known confounders. The higher nonattainment rate could
      suggest that a subgroup of PS children is developmentally disadvantaged.

PMID- 23863117
TI  - Enhanced activity of lysozyme-AgNP conjugate with synergic antibacterial effect
      without damaging the catalytic site of lysozyme.
AB  - CONTEXT: The conjugation of silver nanoparticles (AgNPs) with biomolecules such
      as oligosaccharides, DNA, proteins has attracted great attention of scientists
      recently. OBJECTIVE: In this study, lysozyme-AgNP conjugates were evaluated for
      its synergic antimicrobial effect. MATERIALS AND METHODS: AgNPs were synthesized
      and characterized using UV-Visible, X-ray diffraction analysis (XRD) and atomic
      force microscopy (AFM). AgNP (0-1 mM) was interacted with lysozyme for multi
      spectrophotometric studies. Lysozyme was immobilized on AgNP at different ratios
      and the resulting nano-bio-conjugate was tested against Escherichia coli for
      potent synergic antibacterial effects. RESULTS AND DISCUSSION: A surface plasmon
      peak at 420 nm confirmed the presence of AgNPs and spherical to oval-shaped AgNPs
      were observed by AFM. The particle size was calculated to be 25 nm by XRD
      analysis. The maximum immobilization efficiency (98%) was achieved at 0.01:1
      ratio of enzyme:AgNP. UV-Visible and fluorescence spectral studies revealed the
      binding of AgNPs to lysozyme by the formation of ground-state complex and the
      binding parameters were calculated. Circular dichroism studies confirmed decrease
      by 11% in the alpha-helical and 29.32% in beta-sheets of lysozyme upon AgNP
      interaction. FTIR spectra revealed the binding of AgNP through thiol (-SH)
      linkages of lysozyme. Our results showed that the antimicrobial activity of
      lysozyme-AgNP conjugate was enhanced up to 86% decrease in the cell growth.
      CONCLUSION: In summary, the immobilization of lysozyme on AgNP has yielded a nano
      bio-conjugate with synergistic antibacterial properties.

PMID- 23863118
TI  - In vitro demonstration of enhanced prostate cancer toxicity: pretargeting with
      Bombesin bispecific complexes and targeting with polymer-drug-conjugates.
AB  - BACKGROUND: Bombesin has been used to target Bombesin receptor, a growth
      receptor, which is over-expressed in many cancers, including prostate cancer.
      Polymer-anti-neoplastic-drug-conjugates (PDC) were also developed to reduce non
      specific toxicity and increase tumor toxicity utilizing the enhanced permeability
      and retention effect, benefitting treatment of large tumors with well-established
      vasculature. PURPOSE: If PDCs were delivered by targeted delivery to cancer
      cells, tumor toxicity would be enhanced and non-specific toxicity decreased.
      METHODS: Cardiocyte toxicity was assessed in H9c2 cardiocytes with doxorubicin
      (Dox) or N-terminal DTPA-modified-Doxorubicin-loaded-polyglutamic acid polymers
      (D-Dox-PGA). Therapeutic efficacy of targeted D-Dox-PGA after pretargeting with
      Bombesin-conjugated anti-DTPA-antibody Bispecific Complexes (Bom-BiSpCx) was
      compared to that of Dox in PC3 cells. Bom-BiSpCx was generated by thioether bond
      between Bombesin to Anti-DTPA antibody. RESULTS: D-Dox-PGA was demonstrated to
      have less cardiocyte toxicity (IC50 = 20 ug/ml) than free Dox (1.55 ug/ml, p <
      0.001). However, after pre-targeting of human prostate cancer PC3 cells with Bom
      BiSpCx and targeting with D-Dox-PGA, IC50 (13.2 ug/ml) was about two times less
      than that of Dox (28.5 ug/ml, p < 0.0001). DISCUSSION: Targeted delivery of PDCs
      having lower cardiocyte toxicity enabled higher efficiency cancer cell therapy.
      CONCLUSION: This study may allow development of very efficient targeted prostate
      cancer pro-drug therapy.

PMID- 23863119
TI  - The case for aromatase inhibitors use in oncofertility patients. Should aromatase
      inhibitors be combined with gonadotropin treatment in breast cancer patients
      undergoing ovarian stimulation for fertility preservation prior to chemotherapy?
      A debate.
AB  - Breast cancer is one of the hormone-dependent cancers that may be adversely
      affected by elevated oestrogen or progesterone concentrations, particularly the
      endocrine active (hormone receptor positive) breast cancers. Treatment for breast
      cancer patients aimed at fertility preservation, includes ovarian
      hyperstimulation, the harvest of oocytes, and subsequent cryopreservation of
      oocytes or embryos. Classically, gonadotrophins have been used effectively for
      ovulation induction, a treatment often accompanied by high blood oestrogen
      concentrations produced by the hyperstimulated granulosa cells. Despite the
      uncertainty which surrounds this issue and the lack of clear-cut clinical
      evidence, it is still of major concern that these ensuing high hormone levels
      might be associated with a high risk of recurrence of the cancer. A growing
      number of clinical studies have strongly suggested the benefits of using
      aromatase inhibitors in infertility treatment, both as single agents or as
      adjuncts to FSH-containing ovulation induction regimes in reproductive medicine.
      Combining gonadotrophins with aromatase inhibitors would augment the stimulation
      effect, with a reduced increase in serum concentrations of estradiol. We propose
      to open a debate over the use of aromatase inhibitors in combination with FSH in
      ovulation induction treatment of breast cancer oncofertility patients. As the
      safety of aromatase inhibitors such as letrozole has recently been demonstrated
      in several studies, and there is growing concern over the possible detrimental
      effects of high estradiol levels on breast cancer cells (at least in mouse
      models), the co-administration of letrozole in these patients would reduce both
      the high supraphysiologic serum levels of estradiol and the intratumoral in situ
      production of oestrogen. However, since it is unlikely that a well-founded
      evidence-based justification of this treatment will be formulated in the near
      future, based on well-designed prospective randomised controlled trials, we
      advocate a wider use of aromatase inhibitors in combination with gonadotrophins
      in breast cancer patients, especially those with hormone-receptor-positive
      tumours.

PMID- 23863120
TI  - Magnesium lithospermate B reduces myocardial ischemia/reperfusion injury in rats
      via regulating the inflammation response.
AB  - CONTEXT: Magnesium lithospermate B (MLB), an active polyphenol acid of Danshen
      [Radix Salviae miltiorrhizae (Labiatae)], showed renoprotective, neuroprotective
      and myocardial salvage effects. Previous studies demonstrated that MLB could
      effectively suppress the production of cytokines and their associated signaling
      pathways in activated human T cells. OBJECTIVE: The purpose of this study was to
      examine the beneficial effects of MLB on myocardial ischemia/reperfusion (MI/R)
      injury and to explore its potential mechanisms related to anti-inflammation.
      MATERIALS AND METHODS: Sprague-Dawley rats were grouped as sham group, model
      group and MLB-treated (15, 30 and 60 mg/kg) groups. Animals were subjected to
      MI/R injury by the occlusion of left anterior descending artery for 30 min
      followed by reperfusion for 3 h. At the end of reperfusion, blood samples were
      collected to determine the serum levels of cardiac troponin (cTnI), creatine
      kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL
      1beta) and interleukin 6 (IL-6). Hearts were harvested to assess infarct size,
      histopathological changes and the activity of myeloperoxidase (MPO). The
      expression of phosphor-IkB-alpha and phosphor-nuclear factor kappa B (NF-kappaB)
      were assayed by western blot. RESULTS: MLB administration significantly (p <
      0.05) reduced: (1) ST-segment elevation (0.23 mv), (2) the infarct size (22.5%),
      (3) histological scores of myocardial injury (1.67 score), (4) myocardial injury
      marker enzymes: cTnI (5.64 ng/ml) and CK-MB (49.57 ng/ml) levels, (5) pro
      inflammatory cytokines: TNF-alpha (97.36 pg/ml), IL-1beta (93.35 pg/ml) and IL-6
      (96.84 pg/ml) levels, (6) MPO activity (1.82 U/mg), (7) phosphor-NF-kappaB (0.87)
      and phosphor-IkB-alpha (0.96) expression. DISCUSSION AND CONCLUSION: Our study
      provided evidence that MLB ameliorated the inflammatory process associated with
      MI/R injury via NF-kappaB inactivation.

PMID- 23863121
TI  - Use of antiplatelet drugs in the treatment of acute coronary syndromes.
AB  - Patients with unstable angina pectoris/non-ST-elevation myocardial infarction
      (NSTEMI) should be treated with dual antiplatelet therapy with the use of aspirin
      plus either clopidogrel, prasugrel, or ticagrelor depending on the clinical
      circumstances as discussed in this article. If ticagrelor is used, the dose of
      aspirin must not exceed 100 mg daily. Prasugrel must not be used in patients with
      a history of stroke or transient ischemic attack. Platelet glycoprotein IIb/IIIa
      inhibitors should not be used as part of triple antiplatelet drug therapy if
      there is an increased risk for bleeding or in non-high-risk patients such as
      those with a normal baseline cardiac troponin level, nondiabetics, and those aged
      75 years and older in whom potential benefit may be significantly offset by the
      potential risk of bleeding. Clinical trial data in patients with acute coronary
      syndromes do not support the use of intravenous cangrelor or oral voraxapar in
      the treatment of these patients. 

PMID- 23863123
TI  - The emerging importance of ribosomal dysfunction in the pathogenesis of
      hematologic disorders.
AB  - More than a decade has passed since the initial identification of ribosomal
      protein gene mutations in patients with Diamond-Blackfan anemia (DBA), a
      hematologic disorder that became the founding member of a class of diseases known
      as ribosomopathies. In these diseases, genetic abnormalities that result in
      defective ribosome biogenesis cause strikingly tissue-specific phenotypes in
      patients, specifically bone marrow failure, craniofacial abnormalities and
      skeletal defects. Several animal models and numerous in vitro studies have
      demonstrated that the p53 pathway is central to the ribosomopathy phenotype.
      Additionally, there is mounting evidence of a link between the dysregulation of
      components of the translational machinery and the pathology of various
      malignancies. The importance of the role of ribosomal dysfunction in the
      pathogenesis of hematologic disorders is becoming clearer, and elucidation of the
      underlying mechanisms could have broad implications for both basic cellular
      biology and clinical intervention strategies.

PMID- 23863122
TI  - Perifosine treatment in chronic lymphocytic leukemia: results of a phase II
      clinical trial and in vitro studies.
AB  - Abstract Because of the importance of the phosphoinositide 3-kinase (PI3K)/AKT
      pathway in chronic lymphocytic leukemia (CLL), we evaluated in vitro cytotoxicity
      induced by perifosine, an AKT inhibitor, in CLL lymphocytes and found that the
      mean 50% effective dose (ED50) was 313 nM. We then performed a phase II trial of
      perifosine in patients with relapsed/refractory CLL to assess response, outcomes,
      toxicity and ex vivo correlative measures. After 3 months of treatment, six of
      eight patients showed stable disease, one achieved a partial response and one had
      progressive disease. Median event-free survival and overall survival in all
      patients treated were 3.9 and 9.7 months. Adverse events included hematologic,
      infectious/fever, pain, gastrointestinal and constitutional toxicities.
      Unexpectedly, AKT phosphorylation in CLL lymphocytes from treated patients was
      not correlated with response. Additionally, perifosine did not inhibit AKT
      phosphorylation in cultured CLL lymphocytes. Perifosine is cytotoxic to CLL cells
      in vitro, and largely induces stabilized disease in vivo, with an AKT-independent
      mechanism. 

PMID- 23863125
TI  - Quantitative characterization of the compensating effects of trimethylamine-N
      oxide and guanidine hydrochloride on the dissociation of human cyanmethmoglobin.
AB  - Dynamic light scattering was used to measure the extent of dissociation of human
      cyanmethemoglobin (HbCN) alpha2beta2 tetramers into alphabeta dimers as a
      function of HbCN concentration in the presence of varying concentrations of
      guanidine hydrochloride (GuHCl) and trimethylamine-N-oxide (TMAO). It was found
      that increasing concentrations of GuHCl enhance the dissociation of HbCN, and
      that GuHCl-induced dissociation is progressively inhibited with increasing
      concentrations of TMAO. The effects of both cosolutes upon the free energy of
      HbCN dissociation are shown to be additive. The effect of TMAO on Hb dissociation
      is largely attributed to steric volume exclusion but is partially compensated by
      a small attractive interaction between TMAO and the protein. 

PMID- 23863124
TI  - Inactivation of the phosphoglucomutase gene pgm in Corynebacterium glutamicum
      affects cell shape and glycogen metabolism.
AB  - In Corynebacterium glutamicum formation of glc-1-P (alpha-glucose-1-phosphate)
      from glc-6-P (glucose-6-phosphate) by alpha-Pgm (phosphoglucomutase) is supposed
      to be crucial for synthesis of glycogen and the cell wall precursors trehalose
      and rhamnose. Furthermore, Pgm is probably necessary for glycogen degradation and
      maltose utilization as glucan phosphorylases of both pathways form glc-1-P. We
      here show that C. glutamicum possesses at least two Pgm isoenzymes, the cg2800
      (pgm) encoded enzyme contributing most to total Pgm activity. By inactivation of
      pgm we created C. glutamicum IMpgm showing only about 12% Pgm activity when
      compared to the parental strain. We characterized both strains during cultivation
      with either glucose or maltose as substrate and observed that (i) the glc-1-P
      content in the WT (wild-type) and the mutant remained constant independent of the
      carbon source used, (ii) the glycogen levels in the pgm mutant were lower during
      growth on glucose and higher during growth on maltose, and (iii) the morphology
      of the mutant was altered with maltose as a substrate. We conclude that C.
      glutamicum employs glycogen as carbon capacitor to perform glc-1-P homeostasis in
      the exponential growth phase and is therefore able to counteract limited Pgm
      activity for both anabolic and catabolic metabolic pathways. 

PMID- 23863126
TI  - Urea-induced denaturation of preQ1-riboswitch.
AB  - Urea, a polar molecule with a large dipole moment, not only destabilizes folded
      RNA structures but can also enhance the folding rates of large ribozymes. Unlike
      the mechanism of urea-induced unfolding of proteins, which is well understood,
      the action of urea on RNA has barely been explored. We performed extensive all
      atom molecular dynamics simulations to determine the molecular underpinnings of
      urea-induced RNA denaturation. Urea displays its denaturing power in both
      secondary and tertiary motifs of the riboswitch structure. Our simulations reveal
      that the denaturation of RNA structures is mainly driven by the hydrogen-bonding
      and stacking interactions of urea with the bases. Through detailed studies of the
      simulation trajectories, we found that geminate pairs between urea and bases due
      to hydrogen bonds and stacks persist only ~0.1-1 ns, which suggests that the urea
      base interaction is highly dynamic. Most importantly, the early stage of base
      pair disruption is triggered by penetration of water molecules into the
      hydrophobic domain between the RNA bases. The infiltration of water into the
      narrow space between base pairs is critical in increasing the accessibility of
      urea to transiently disrupted bases, thus allowing urea to displace inter-base
      hydrogen bonds. This mechanism--water-induced disruption of base pairs resulting
      in the formation of a "wet" destabilized RNA followed by solvation by urea--is
      the exact opposite of the two-stage denaturation of proteins by urea. In the
      latter case, initial urea penetration creates a dry globule, which is
      subsequently solvated by water, leading to global protein unfolding. Our work
      shows that the ability to interact with both water and polar or nonpolar
      components of nucleotides makes urea a powerful chemical denaturant for nucleic
      acids.

PMID- 23863128
TI  - A crown-shaped 24-molybdate cluster constructed by organotriphosphonate ligand.
AB  - A crown-shaped organic-inorganic hybrid polyoxomolybdate,
      Na5[H7{N(CH2PO3)3}Mo6O16(OH) (H2O)4]4.18H2O (1) has been presented and
      characterized. Such an intriguing structure consists of a 24-molybdenum-membered
      polyanion constructed by organotriphosphonate ligands, which represents the
      highest nuclearity of metal atoms in the area of organophosphonate-based
      polyoxometalates. 

PMID- 23863127
TI  - Maternal history of child abuse moderates the association between daily stress
      and diurnal cortisol in pregnancy: a pilot study.
AB  - Previous research on the association between maternal daily stress and cortisol
      in pregnancy has yielded inconsistent findings. However, past studies have not
      considered whether stressful experiences in childhood impact maternal cortisol
      regulation in pregnancy. In this pilot study, we aimed to examine whether the
      association between maternal daily stress and cortisol differed according to
      maternal history of child abuse. Forty-one women provided salivary cortisol
      samples at wake-up, 30 min after wake-up, and bedtime for 3 days at three times
      over second and third trimesters of pregnancy. On each day of cortisol collection
      women reported their daily stress. Women reported child abuse experiences prior
      to age 18 years by completing 15 items from the Adverse Childhood Experiences
      Scale. Twenty-one percent (N = 9) of women reported a history of child sexual
      abuse (CSA), 44% (N = 18) reported a history of non-sexual child abuse and 34% (N
      = 14) reported no history of child abuse. Hierarchical Linear Modeling (HLM)
      analyses revealed that stress in the day prior was associated with increases in
      morning cortisol in women with CSA histories compared to women with non-sexual
      abuse histories or no history of child abuse. Increases in evening cortisol were
      associated with increases in daily stress in women with CSA histories compared to
      women with non-sexual abuse histories or no history of child abuse. Results
      reveal a dynamic association between daily stress and cortisol in pregnancy and
      suggest that patterns differ according to maternal child abuse history.

PMID- 23863129
TI  - Exposure chambers for studying the partitioning of atmospheric PAHs in
      environmental compartments: validation and calibration using experimental and
      computational approaches.
AB  - The environmental partitioning of atmospheric polycyclic aromatic hydrocarbons
      (PAHs) conditions their entry into food chains and subsequent risks for human
      health. The need for new experimental exposure devices for elucidating the
      mechanisms governing ecosystemic PAH transfer motivated the elaboration of an
      original small-scale exposure chamber (EC). A dual approach pairing
      experimentation and computational fluid dynamics (CFD) was selected to provide
      comprehensive validation of this EC as a tool to study the transfer and
      biological effects of atmospheric PAH pollution in microsystems. Soil samples and
      passive air samplers (PASs) were exposed to atmospheric pollution by phenanthrene
      (PHE), a gaseous PAH, for 2 weeks in examples of the EC being tested, set up
      under different conditions. Dynamic concentrations of atmospheric PHE and its
      uptake by PASs were simulated with CFD, results showing homogeneous distribution
      and constant atmospheric PHE concentrations inside the ECs. This work provides
      insight into the setting of given concentrations and pollution levels when using
      such ECs. The combination of experimentation and CFD is a successful ECs
      calibration method that should be developed with other semivolatile organic
      pollutants, including those that tend to partition in the aerosol phase. 

PMID- 23863130
TI  - Multifaceted impairments of impulsivity in cannabis users?

PMID- 23863131
TI  - The nature of the memory buffer in implicit learning: learning Chinese tonal
      symmetries.
AB  - Previous research has established that people can implicitly learn chunks, which
      (in terms of formal language theory) do not require a memory buffer to process.
      The present study explores the implicit learning of nonlocal dependencies
      generated by higher than finite-state grammars, specifically, Chinese tonal
      retrogrades (i.e. centre embeddings generated from a context-free grammar) and
      inversions (i.e. cross-serial dependencies generated from a mildly context
      sensitive grammar), which do require buffers (for example, last in-first out and
      first in-first out, respectively). People were asked to listen to and memorize
      artificial poetry instantiating one of the two grammars; after this training
      phase, people were informed of the existence of rules and asked to classify new
      poems, while providing attributions of the basis of their judgments. People
      acquired unconscious structural knowledge of both tonal retrogrades and
      inversions. Moreover, inversions were implicitly learnt more easily than
      retrogrades constraining the nature of the memory buffer in computational models
      of implicit learning. 

PMID- 23863132
TI  - Health professionals for global health: include dental personnel upfront!
AB  - The Global Health Beyond 2015 was organized in Stockholm in April 2013, which was
      announced as public engagement and where the dialogue focused on three main
      themes: social determinants of health, climate change and the non-communicable
      diseases. This event provided opportunity for both students and health
      professionals to interact and brainstorm ideas to be formalized into Stockholm
      Declaration on Global Health. Amongst the active participation of various health
      professionals, one that was found significantly missing was that of oral health.
      Keeping this as background in this debate, a case for inclusion of oral health
      professions is presented by organizing the argument in four areas: education,
      evidence base, political will and context and what each one offers at a time when
      Scandinavia is repositioning itself in global health. 

PMID- 23863133
TI  - Preparation of surface-attached polymer layers by thermal or photochemical
      activation of alpha-diazoester moieties.
AB  - We report on the attachment of polymer monolayers or surface-attached, polymer
      networks onto SiO2 and/or polymer surfaces using thermo- and photoreactive alpha
      diazoester groups. In the prior case, the alpha-diazoester groups are introduced
      into the system in the form of self-assembled monolayers of appropriately
      functionalized silanes. The monolayer decorated substrates are coated by polymer
      films and the alpha-diazoester groups in the monolayer are activated by heat or
      irradiation with UV-light. Upon activation, they cleave off nitrogen and the
      resulting carbene intermediates insert into C-H bonds of neighboring polymer
      chains. As a result of this binding process, surface-attached monolayers of the
      deposited polymer are obtained. When the polymers themselves carry such reactive
      moieties, the photo- or thermal activation leads to cross-linking of the polymers
      and thin surface-attached polymer networks result from the same process. The
      formation of the surface-attached layer is studied as a function of activation
      conditions, especially the temperature and the wavelength of the light used in
      the process. 

PMID- 23863134
TI  - Enhanced antitumor activity of erlotinib in combination with the Hsp90 inhibitor
      CH5164840 against non-small-cell lung cancer.
AB  - Inhibition of heat shock protein 90 (Hsp90) can lead to degradation of multiple
      client proteins, which are involved in tumor progression. Epidermal growth factor
      receptor (EGFR) is one of the most potent oncogenic client proteins of Hsp90.
      Targeted inhibition of EGFR has shown clinical efficacy in the treatment of
      patients with non-small-cell lung cancer (NSCLC). However, primary and acquired
      resistance to the existing EGFR inhibitors is a major clinical problem. In the
      present study, we investigated the effect of the novel Hsp90 inhibitor CH5164840
      on the antitumor activity of erlotinib. The NSCLC cell lines and xenograft models
      were treated with CH5164840 and erlotinib to examine their mechanisms of action
      and cell growth inhibition. We found that CH5164840 showed remarkable antitumor
      activity against NSCLC cell lines and xenograft models. The addition of CH5164840
      enhanced the antitumor activity of erlotinib against NCI-H292 EGFR-overexpressing
      xenograft models. Phosphorylation of Stat3 increased with erlotinib treatment in
      NCI-H292 cells, which was abrogated by Hsp90 inhibition. Furthermore, in a NCI
      H1975 T790M mutation erlotinib-resistant model, CH5164840 enhanced the antitumor
      activity of erlotinib despite the low efficacy of erlotinib treatment alone. In
      addition, ERK signaling was effectively suppressed by combination treatment with
      erlotinib and CH5164840 in a NCI-H1975 erlotinib-resistant model. Taken together,
      these data indicate that CH5164840 has potent antitumor activity and is highly
      effective in combination with erlotinib against NSCLC tumors with EGFR
      overexpression and mutations. Our results support the therapeutic potential of
      CH5164840 as a Hsp90 inhibitor for combination therapy with EGFR-targeting agents
      against EGFR-addicted NSCLC. 

PMID- 23863135
TI  - An artificial light-harvesting array constructed from multiple Bodipy dyes.
AB  - An artificial light-harvesting array, comprising 21 discrete chromophores
      arranged in a rational manner, has been synthesized and characterized fully. The
      design strategy follows a convergent approach that leads to a molecular-scale
      funnel, having an effective chromophore concentration of 0.6 M condensed into ca.
      55 nm(3), able to direct the excitation energy to a focal point. A cascade of
      electronic energy-transfer steps occurs from the rim to the focal point, with the
      rate slowing down as the exciton moves toward its ultimate target. Situated
      midway along each branch of the V-shaped array, two chromophoric relays differ
      only slightly in terms of their excitation energies, and this situation
      facilitates reverse energy transfer. Thus, the excitation energy becomes spread
      around the array, a situation reminiscent of a giant holding pattern for the
      photon that can sample many different chromophores before being trapped by the
      terminal acceptor. At high photon flux under conditions of relatively slow off
      load to a device, such as a solar cell, electronic energy transfer encounters one
      or more barriers that hinder forward progress of the exciton and thereby delays
      arrival of the second photon. Preliminary studies have addressed the ability of
      the array to function as a sensitizer for amorphous silicon solar cells. 

PMID- 23863136
TI  - The importance of landscape and spatial structure for hymenopteran-based food
      webs in an agro-ecosystem.
AB  - 1. Understanding the environmental factors that structure biodiversity and food
      webs among communities is central to assess and mitigate the impact of landscape
      changes. 2. Wildflower strips are ecological compensation areas established in
      farmland to increase pollination services and biological control of crop pests
      and to conserve insect diversity. They are arranged in networks in order to
      favour high species richness and abundance of the fauna. 3. We describe results
      from experimental wildflower strips in a fragmented agricultural landscape,
      comparing the importance of landscape, of spatial arrangement and of vegetation
      on the diversity and abundance of trap-nesting bees, wasps and their enemies, and
      the structure of their food webs. 4. The proportion of forest cover close to the
      wildflower strips and the landscape heterogeneity stood out as the most
      influential landscape elements, resulting in a more complex trap-nest community
      with higher abundance and richness of hosts, and with more links between species
      in the food webs and a higher diversity of interactions. We disentangled the
      underlying mechanisms for variation in these quantitative food web metrics. 5. We
      conclude that in order to increase the diversity and abundance of pollinators and
      biological control agents and to favour a potentially stable community of cavity
      nesting hymenoptera in wildflower strips, more investment is needed in the
      conservation and establishment of forest habitats within agro-ecosystems, as a
      reservoir of beneficial insect populations.

PMID- 23863137
TI  - miRNAs in development and pathogenesis of the nervous system.
AB  - The human nervous system expresses approximately 70% of all miRNAs (microRNAs).
      Changing levels of certain ubiquitous and brain-specific miRNAs shape the
      development and function of the nervous system. It is becoming clear that
      misexpression of some miRNAs can contribute towards neurodevelopmental disorders.
      In the present article, we review the current knowledge of the role of miRNAs in
      development and pathogenesis of the nervous system. 

PMID- 23863138
TI  - The primary target of let-7 microRNA.
AB  - The let-7 miRNA (microRNA) is an essential regulator of development from nematode
      worms to humans. Altered expression of let-7 results in larval arrest or
      lethality in Caenorhabditis elegans. Likewise, under- or over-expression of let-7
      in human cells can result in cellular overproliferation or halted cell division
      respectively. Thus the biogenesis of this critical miRNA is controlled at
      multiple levels. An unexpected mechanism for regulating the initial processing of
      let-7 was recently found to involve the let-7 miRNA itself. The mature let-7
      miRNA along with its effector protein, Argonaute, were shown to bind to a site in
      the primary transcripts produced by the let-7 gene. This interaction enhances
      processing through a novel auto-regulatory feedback loop. This discovery
      highlights a new role for the miRNA complex in regulating miRNA biogenesis and
      enriches the classes of RNAs targeted by Argonaute. 

PMID- 23863139
TI  - The multifunctional RNase XRN2.
AB  - Different classes of RNA function in various cellular processes, and their
      biogenesis and turnover involve diverse RNases for processing and degradation.
      XRN2 is a 5'->3' exoribonuclease that is evolutionarily conserved in eukaryotes.
      It is predominantly localized in the nucleus and recognizes single-stranded RNA
      with a 5'-terminal monophosphate to degrade it processively to mononucleotides.
      In the present paper, we review functions of XRN2 and its cofactors in
      maturation, surveillance and activity control of several classes of RNA such as
      pre-mRNA (precursor mRNA), rRNA and snoRNA (small nucleolar RNA). 

PMID- 23863140
TI  - Intron excision from precursor tRNA molecules in mammalian cells requires ATP
      hydrolysis and phosphorylation of tRNA-splicing endonuclease components.
AB  - The process of tRNA splicing entails removal of an intron by TSEN (tRNA-splicing
      endonuclease) and ligation of the resulting exon halves to generate functional
      tRNAs. In mammalian cells, the RNA kinase CLP1 (cleavage and polyadenylation
      factor I subunit) associates with TSEN and phosphorylates the 3' exon at the 5'
      end in vitro, suggesting a role for CLP1 in tRNA splicing. Interestingly, recent
      data suggest that the ATP-binding and/or hydrolysis capacity of CLP1 is required
      to enhance pre-tRNA cleavage. In vivo, the lack of CLP1 kinase activity leads to
      progressive motor neuron loss and accumulation of novel 5' leader-5' exon tRNA
      fragments. We have extended the investigation of the biochemical requirements in
      pre-tRNA splicing and found that beta-gamma-hydrolysable ATP is crucial for the
      productive generation of exon halves. In addition, we provide evidence that
      phosphorylation of the TSEN complex components supports efficient pre-tRNA
      cleavage. Taken together, our data improve the mechanistic understanding of
      mammalian pre-tRNA processing and its regulation. 

PMID- 23863141
TI  - Cellular functions of the microprocessor.
AB  - The microprocessor is a complex comprising the RNase III enzyme Drosha and the
      double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8
      gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8
      recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent
      global analyses of microprocessor and Dicer proteins have suggested novel
      functions for these components independent of their role in miRNA biogenesis. A
      HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking
      immunoprecipitation) experiment designed to identify novel substrates of the
      microprocessor revealed that this complex binds and regulates a large variety of
      cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs
      not only regulates transcript levels, but also modulates alternative splicing
      events, independently of miRNA function. Importantly, DGCR8 can also associate
      with other nucleases, suggesting the existence of alternative DGCR8 complexes
      that may regulate the fate of a subset of cellular RNAs. The aim of the present
      review is to provide an overview of the diverse functional roles of the
      microprocessor. 

PMID- 23863142
TI  - Biogenesis and function of non-coding RNAs in muscle differentiation and in
      Duchenne muscular dystrophy.
AB  - It is now becoming largely accepted that the non-coding portion of the genome,
      rather than its coding counterpart, is likely to account for the greater
      complexity of higher eukaryotes. Moreover, non-coding RNAs have been demonstrated
      to participate in regulatory circuitries that are crucial for development and
      differentiation. Whereas the biogenesis and function of small non-coding RNAs,
      particularly miRNAs (microRNAs), has been extensively clarified in many
      eukaryotic systems, very little is known about the long non-coding counterpart of
      the transcriptome. In the present review, we revise the current knowledge of how
      small non-coding RNAs and lncRNAs (long non-coding RNAs) impinge on circuitries
      controlling proper muscle differentiation and homoeostasis and how their
      biogenesis is regulated. Moreover, we provide new insights into an additional
      mechanism of post-transcriptional regulation mediated by lncRNAs, which, acting
      as miRNA 'sponges', have an impact on the distribution of miRNA molecules on
      their targets with features similar to those described for ceRNAs (competing
      endogenous RNAs). 

PMID- 23863143
TI  - Multiple products from microRNA transcripts.
AB  - A single transcript sometimes codes for more than one product. In bacteria, and
      in a few exceptional animal lineages, many genes are organized into operons:
      clusters of open reading frames that are transcribed together in a single
      polycistronic transcript. However, polycistronic transcripts are rare in
      eukaryotes. One notable exception is that of miRNAs (microRNAs), small RNAs that
      regulate gene expression at the post-transcriptional level. The primary
      transcripts of miRNAs commonly produce more than one functional product, by at
      least three different mechanisms. miRNAs are often produced from polycistronic
      transcripts together with other miRNA precursors. Also, miRNAs frequently derive
      from protein-coding gene introns. Finally, each miRNA precursor can produce two
      mature miRNA products. We argue, in the present review, that miRNAs are
      frequently hosted in transcripts coding for multiple products because new miRNA
      precursor sequences that arise by chance in transcribed regions are more likely
      to become functional miRNAs during evolution. 

PMID- 23863144
TI  - Argonaute and GW182 proteins: an effective alliance in gene silencing.
AB  - Argonaute proteins interact with small RNAs and facilitate small RNA-guided gene
      silencing processes. Small RNAs guide Argonaute proteins to distinct target sites
      on mRNAs where Argonaute proteins interact with members of the GW182 protein
      family (also known as GW proteins). In subsequent steps, GW182 proteins mediate
      the downstream steps of gene silencing. The present mini-review summarizes and
      discusses our current knowledge of the molecular basis of Argonaute-GW182 protein
      interactions. 

PMID- 23863146
TI  - Discovery of novel small RNAs in the quest to unravel genome complexity.
AB  - The different RNA populations within the cell, or the 'RNAome', form a complex
      and integral layer of gene regulation. In particular, small non-coding RNAs such
      as microRNAs have been shown to regulate as much as half of all genes expressed
      in mammals. The recent discovery of novel small RNAs derived from tRNAs, snoRNAs
      and Y RNAs, as well as the development of techniques that can reduce sequencing
      bias of these molecules, is slowly helping us to unveil the secrets of the
      genome. 

PMID- 23863145
TI  - Terminal loop-mediated regulation of miRNA biogenesis: selectivity and
      mechanisms.
AB  - Regulating the expression of individual miRNAs (microRNAs) is important for cell
      development and function. The up- or down-regulation of the processing of
      specific miRNA precursors to the mature active form represents one tool to
      control miRNA concentration and is mediated by proteins that recognize the
      terminal loop of the RNA precursors. Terminal loop recognition is achieved by the
      combined action of several RNA-binding domains. The proteins can then regulate
      the processing by recruiting RNA enzymes, changing the RNA structure and
      preventing or enhancing the accessibility and processing activity of the core
      processing complexes. The present review focuses on how terminal loop-binding
      proteins recognize their RNA targets and mediate their regulatory function(s),
      and highlights how terminal loop-mediated regulation relates to the broader
      regulation of mRNA metabolism. 

PMID- 23863147
TI  - Small nuclear RNAs and mRNAs: linking RNA processing and transport to spinal
      muscular atrophy.
AB  - The splicing of pre-mRNA by the spliceosome is a characteristic feature of
      eukaryotic cells, dependent on a group of snRNPs (small nuclear
      ribonucleoproteins). These splicing snRNPs have a complex assembly pathway
      involving multiple steps that take place in different regions of the cell, which
      is reflected in their complex subcellular distribution. Vital to the assembly of
      splicing snRNPs is the protein SMN (survival of motor neurons). In multicellular
      organisms, SMN acts in the cytoplasm, together with its associated protein
      complex to assemble a heptameric ring of proteins called the Sm proteins as an
      early stage in splicing snRNP assembly. A deficiency of the SMN protein results
      in the inherited neurodegenerative condition SMA (spinal muscular atrophy), a
      leading cause of infant mortality specifically affecting spinal motor neurons. It
      has long been a puzzle how lowered levels of a protein required for a process as
      fundamental as splicing snRNP assembly can result in a condition with such a
      definite cell-type-specificity. The present review highlights recent research
      that points to wider roles in RNA metabolism for both SMN itself and the Sm
      proteins with which it is linked. 

PMID- 23863148
TI  - RNAi pathways in the recognition of foreign RNA: antiviral responses and host
      parasite interactions in nematodes.
AB  - The nematode Caenorhabditis elegans was the first animal for which RNAi (RNA
      interference) in response to exogenous triggers was shown experimentally and
      subsequently the molecular components of the RNAi pathway have been characterized
      in some detail. However, the function of RNAi in the life cycle of nematodes in
      the wild is still unclear. In the present article, we argue that RNAi could be
      used in nematodes as a mechanism to sense and respond to foreign RNA that the
      animal might be exposed to either through viral infection or through ingestion of
      food sources. This could be of potential importance to the life cycle of
      parasitic nematodes as they ingest RNA from different hosts at different points
      during their life cycle. We postulate that RNA ingested from the host could be
      used by the parasite to regulate its own genes, through the amplification
      mechanism intrinsic to the nematode RNAi pathway. 

PMID- 23863150
TI  - Talks about TORCs: recent advancesin target of rapamycin signalling. On mTOR
      nomenclature.
AB  - In the present article, I discuss recent developments in the naming of the TOR
      (target of rapamycin) protein. In particular, I address the issue of mammalian
      target of rapamycin (mTOR) versus the newer mechanistic target of rapamycin
      (MTOR). mTOR is the name given by the TOR community almost two decades ago and
      widely used ever since. MTOR is a name recently imposed on the TOR community by
      database curators and used mainly by newcomers. I argue that MTOR is causing
      needless confusion in the field, and conclude that one should use the name mTOR. 

PMID- 23863149
TI  - Functional diversification of Argonautes in nematodes: an expanding universe.
AB  - In the last decade, many diverse RNAi (RNA interference) pathways have been
      discovered that mediate gene silencing at epigenetic, transcriptional and post
      transcriptional levels. The diversity of RNAi pathways is inherently linked to
      the evolution of Ago (Argonaute) proteins, the central protein component of RISCs
      (RNA-induced silencing complexes). An increasing number of diverse Agos have been
      identified in different species. The functions of most of these proteins are not
      yet known, but they are generally assumed to play roles in development, genome
      stability and/or protection against viruses. Recent research in the nematode
      Caenorhabditis elegans has expanded the breadth of RNAi functions to include
      transgenerational epigenetic memory and, possibly, environmental sensing. These
      functions are inherently linked to the production of secondary siRNAs (small
      interfering RNAs) that bind to members of a clade of WAGOs (worm-specific Agos).
      In the present article, we review briefly what is known about the evolution and
      function of Ago proteins in eukaryotes, including the expansion of WAGOs in
      nematodes. We postulate that the rapid evolution of WAGOs enables the exceptional
      functional plasticity of nematodes, including their capacity for parasitism. 

PMID- 23863151
TI  - Conserved sequence motifs and the structure of the mTOR kinase domain.
AB  - The atypical serine/threonine kinase mTOR (mammalian target of rapamycin) is a
      central regulator of cell growth and metabolism. mTOR is part of two multisubunit
      signalling complexes, mTORC1 and mTORC2. Although many aspects of mTOR signalling
      are understood, the lack of high-resolution structures impairs a detailed
      understanding of complex assembly, function and regulation. The structure of the
      kinase domain is of special interest for the development of mTOR inhibitors as
      anti-cancer agents. A homology model of the mTOR kinase domain was derived from
      the structure of PI3Ks (phosphoinositide 3-kinases). More recently, the crystal
      structure of the catalytic domain of human mTOR was determined, providing long
      awaited structural insight into the architecture of mTOR. Interestingly, the
      homology model predicted several aspects of the crystal structure. In the present
      paper, we revisit the homology model in the context of the now available crystal
      structure of the mTOR kinase domain. 

PMID- 23863152
TI  - Regulation of insulin receptor substrate-1 by mTORC2 (mammalian target of
      rapamycin complex 2).
AB  - mTOR (mammalian target of rapamycin) responds to the presence of nutrients,
      energy and growth factors to link cellular metabolism, growth and proliferation.
      The rapamycin-sensitive mTORC (mTOR complex) 1 activates the translational
      regulator S6K (S6 kinase), leading to increased protein synthesis in the presence
      of nutrients. On the other hand, the rapamycin-insensitive mTORC2 responds to the
      presence of growth factors such as insulin by phosphorylating Akt to promote its
      maturation and allosteric activation. We recently found that mTORC2 can also
      regulate insulin signalling at the level of IRS-1 (insulin receptor substrate-1).
      Whereas mTORC1 promotes IRS-1 serine phosphorylation that is linked to IRS-1 down
      regulation, we uncovered that mTORC2 mediates its degradation. In mTORC2
      disrupted cells, inactive IRS-1 accumulated despite undergoing phosphorylation at
      the mTORC1-mediated serine sites. Defective IRS-1 degradation was due to
      attenuated expression of the CUL7 (Cullin 7) ubiquitin ligase substrate-targeting
      sub-unit Fbw8. mTORC2 and Fbw8 co-localize at the membrane where mTORC2
      phosphorylates Ser86 to stabilize Fbw8 and promotes its cytosolic localization
      upon insulin stimulation. Under conditions of chronic insulin exposure, inactive
      serine-phosphorylated IRS-1 and Fbw8 co-localize to the cytosol where the former
      becomes ubiquitylated via CUL7/Fbw8. Thus mTORC2 negatively feeds back to IRS-1
      via control of Fbw8 stability and localization. Our findings reveal that, in
      addition to persistent mTORC1 signalling, increased mTORC2 signals can promote
      insulin resistance due to mTORC2-mediated degradation of IRS-1. 

PMID- 23863153
TI  - Nutrients and growth factors in mTORC1 activation.
AB  - Growth factors and nutrients regulate the mTORC1 [mammalian (or mechanistic)
      target of rapamycin complex 1] by different mechanisms. The players that link
      growth factors and mTORC1 activation have been known for several years and mouse
      models have validated its relevance for human physiology and disease. In contrast
      with the picture for growth factor signalling, the means by which nutrient
      availability leads to mTORC1 activation have remained elusive until recently,
      with the discovery of the Rag GTPases upstream of mTORC1. The Rag GTPases recruit
      mTORC1 to the outer lysosomal surface, where growth factor signalling and
      nutrient signalling converge on mTORC1 activation. A mouse model of constitutive
      RagA activity has revealed qualitative differences between growth-factor- and
      nutrient-dependent regulation of mTORC1. Regulation of mTORC1 activity by the Rag
      GTPases in vivo is key for enduring early neonatal starvation, showing its
      importance for mammalian physiology. 

PMID- 23863154
TI  - A growing role for mTOR in promoting anabolic metabolism.
AB  - mTOR [mammalian (or mechanistic) target of rapamycin] is a protein kinase that,
      as part of mTORC1 (mTOR complex 1), acts as a critical molecular link between
      growth signals and the processes underlying cell growth. Although there has been
      intense interest in the upstream mechanisms regulating mTORC1, the full
      repertoire of downstream molecular events through which mTORC1 signalling
      promotes cell growth is only recently coming to light. It is now recognized that
      mTORC1 promotes cell growth and proliferation in large part through the
      activation of key anabolic processes. Through a variety of downstream targets,
      mTORC1 alters cellular metabolism to drive the biosynthesis of building blocks
      and macromolecules fundamentally essential for cell growth, including proteins,
      lipids and nucleic acids. In the present review, we focus on the metabolic
      functions of mTORC1 as they relate to the control of cell growth and
      proliferation. As mTORC1 is aberrantly activated in a number of tumour syndromes
      and up to 80% of human cancers, we also discuss the importance of this mTORC1
      driven biosynthetic programme in tumour growth and progression. 

PMID- 23863155
TI  - Many roads from mTOR to eIF4F.
AB  - The process of cell growth depends on a complex co-ordinated programme of
      macromolecular synthesis that can be tuned to environmental constraints. In
      eukaryotes, the mTOR [mammalian (or mechanistic) target of rapamycin] signalling
      pathway is a master regulator of this process, in part by regulating mRNA
      translation through control of the eIF4F (eukaryotic initiation factor 4F)
      initiation complex. The present review discusses the role of this relationship in
      mTOR-regulated gene expression, and its contribution to phenotypes associated
      with deregulated mTOR signalling, such as cancer. 

PMID- 23863156
TI  - Role of PI3K, mTOR and Akt2 signalling in hepatic tumorigenesis via the control
      of PKM2 expression.
AB  - To sustain increased growth, rapidly proliferating cells, such as tumour cells,
      undergo metabolic adaptations. In recent years, the mechanisms of glycolysis
      activation as a key metabolic adaptation in proliferating cells became the topic
      of intense research. Although this phenomenon was described more than 50 years
      ago by Otto Warburg, the molecular mechanisms remained elusive. Only recently, it
      was demonstrated that the expression of specific glycolytic enzymes, namely PKM2
      (pyruvate kinase M2) and HK2 (hexokinase 2), occurs simultaneously with the
      glycolytic addiction of cancer cells. The PI3K (phosphoinositide 3-kinase)/mTOR
      [mammalian (or mechanistic) target of rapamycin] signalling pathway is a central
      signalling hub co-ordinating the growth in response to growth factor signalling
      and nutrient availability. Not surprisingly, it is found to be activated in the
      majority of the tumour cells. In the present article, we discuss the requirement
      of different PI3K/mTOR downstream effectors for the metabolic adaptation in liver
      cancer cells driven by this signalling pathway. We provide evidence for a
      selective involvement of the mTOR target Akt2 in tumoral growth. In addition,
      PTEN (phosphatase and tensin homologue deleted on chromosome 10)-negative human
      hepatocellular carcinoma cell lines display an up-regulation of PKM2 expression
      in an Akt2-dependent manner, providing an advantage for cell proliferation and
      anchorage-independent growth. Our data have implications on the link between the
      metabolic action of insulin signal transduction and tumorigenesis, identifying
      Akt2 as a potential therapeutical target in liver malignancies depending on
      cancer genotype. 

PMID- 23863157
TI  - mTORC1 regulates the efficiency and cellular capacity for protein synthesis.
AB  - mTORC1 (mammalian target of rapamycin complex 1) is activated by nutrients,
      growth factors and certain hormones. Signalling downstream of mTORC1 promotes
      protein synthesis by both activating the processes of translation initiation and
      elongation, in the short term, and the production of new ribosomes, in the longer
      term. mTORC1 signalling stimulates the translation of the mRNAs encoding the
      ribosomal proteins, activates RNA polymerases I and III, which make the rRNAs,
      and promotes the processing of the precursor for the main rRNAs. Taken together,
      these effects allow mTORC1 signalling to drive cell growth and proliferation. 

PMID- 23863158
TI  - Immune responses of macrophages and dendritic cells regulated by mTOR signalling.
AB  - The innate myeloid immune system is a complex network of cells that protect
      against disease by identifying and killing pathogens and tumour cells, but it is
      also implicated in homoeostatic mechanisms such as tissue remodelling and wound
      healing. Myeloid phagocytes such as monocytes, macrophages or dendritic cells are
      at the basis of controlling these immune responses in all tissues of the body. In
      the present review, we summarize recent studies demonstrating that mTOR
      [mammalian (or mechanistic) target of rapamycin] regulates innate immune
      reactions in macrophages and dendritic cells. The mTOR pathway serves as a
      decision maker to control the cellular response to pathogens and tumours by
      regulating the expression of inflammatory mediators such as cytokines, chemokines
      or interferons. In addition to various in vivo mouse models, kidney transplant
      patients under mTOR inhibitor therapy allowed the elucidation of important innate
      immune functions regulated by mTOR in humans. The role of the mTOR pathway in
      macrophages and dendritic cells enhances our understanding of the immune system
      and suggests new therapeutic avenues for the regulation of pro- versus anti
      inflammatory mediators with potential relevance to cancer therapy, the design of
      novel adjuvants and the control of distinct infectious and autoimmune diseases. 

PMID- 23863159
TI  - Target of rapamycin (TOR) kinase in Trypanosoma brucei: an extended family.
AB  - The complex life cycle of Trypanosoma brucei provides an excellent model system
      to understand signalling pathways that regulate development. We described
      previously the classical functions of TOR (target of rapamycin) 1 and TOR2 in T.
      brucei. In a more recent study, we described a novel TOR kinase, named TOR4,
      which regulates differentiation from the proliferative infective form to the
      quiescent form. In contrast with TOR1 loss-of-function, down-regulation of TOR4
      triggers an irreversible differentiation process through the development of the
      insect pre-adapted quiescent form. TOR4 governs a signalling pathway distinct
      from those controlled by the conventional TOR complexes TORC1 and TORC2.
      Depletion of TOR4 induces all well-known characteristics of the quiescent
      developmental stage in trypanosomes, including expression of the PAD (proteins
      associated with differentiation) surface proteins and transcriptional down
      regulation of the VSG (variant surface glycoprotein) gene. TOR4 kinase forms a
      structurally and functionally distinct complex named TORC4. TOR4 associates with
      LST8 (lethal with sec-13 protein 8) and other factors including an armadillo
      domain-containing protein and the major vault protein, which probably serves as a
      scaffold for this kinase. Research in T. brucei, a protozoan parasite that
      diverged from the eukaryotic tree early in evolution, may help to uncover new
      functions of TOR kinases. 

PMID- 23863160
TI  - The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient
      homoeostasis.
AB  - In order for cells to divide in a proficient manner, they must first double their
      biomass, which is considered to be the main rate-limiting phase of cell
      proliferation. Cell growth requires an abundance of energy and biosynthetic
      precursors such as lipids and amino acids. Consequently, the energy and nutrient
      status of the cell is acutely monitored and carefully maintained. mTORC1
      [mammalian (or mechanistic) target of rapamycin complex 1] is often considered to
      be the master regulator of cell growth that enhances cellular biomass through up
      regulation of protein translation. In order for cells to control cellular
      homoeostasis during growth, there is close signalling interplay between mTORC1
      and two other protein kinases, AMPK (AMP-activated protein kinase) and ULK1 (Unc
      51-like kinase 1). This kinase triad collectively senses the energy and nutrient
      status of the cell and appropriately dictates whether the cell will actively
      favour energy- and amino-acid-consuming anabolic processes such as cellular
      growth, or energy- and amino-acid-generating catabolic processes such as
      autophagy. The present review discusses important feedback mechanisms between
      these three homoeostatic protein kinases that orchestrate cell growth and
      autophagy, with a particular focus on the mTORC1 component raptor (regulatory
      associated protein of mammalian target of rapamycin), as well as the autophagy
      initiating kinase ULK1. 

PMID- 23863161
TI  - Akt/mTOR signalling in myelination.
AB  - Akt signalling has emerged as one of the major pathways involved in myelination,
      implicated in the regulation of several steps during the development of
      myelinating Schwann cells and oligodendrocytes. One of the main pathways
      intimately linked with Akt is mTOR [mammalian (or mechanistic) target of
      rapamycin] signalling. Recent evidence suggests that many processes attributed to
      the Akt pathway in myelination depend, at least partly, on mTOR signalling. In
      the present mini-review, we summarize the major aspects of Akt/mTOR signalling
      and myelination, and how they appear to be linked. We focus on the PNS
      (peripheral nervous system), but also cover the key points of CNS (central
      nervous system) myelination, pointing out differences and similarities between
      the PNS and the CNS. 

PMID- 23863162
TI  - Rheb and Rags come together at the lysosome to activate mTORC1.
AB  - mTORC1 (mammalian target of rampamycin complex 1) is a highly conserved protein
      complex regulating cell growth and metabolism via its kinase mTOR (mammalian
      target of rapamycin). The activity of mTOR is under the control of various
      GTPases, of which Rheb and the Rags play a central role. The presence of amino
      acids is a strict requirement for mTORC1 activity. The heterodimeric Rag GTPases
      localize mTORC1 to lysosomes by their amino-acid-dependent interaction with the
      lysosomal Ragulator complex. Rheb is also thought to reside on lysosomes to
      activate mTORC1. Rheb is responsive to growth factors, but, in conjunction with
      PLD1 (phospholipase D1), is also an integral part of the machinery that
      stimulates mTORC1 in response to amino acids. In the present article, we provide
      a brief overview of novel mechanisms by which amino acids affect the function of
      Rags. On the basis of existing literature, we postulate that Rheb is activated at
      the Golgi from where it will travel to lysosomes. Maturation of endosomes into
      lysosomes may be required to assure a continuous supply of GTP-bound Rheb for
      mTORC1 activation, which may help to drive the maturation process. 

PMID- 23863163
TI  - Adaptation to chronic mTOR inhibition in cancer and in aging.
AB  - The mTOR [mammalian (or mechanistic) target of rapamycin] protein kinase co
      ordinates catabolic and anabolic processes in response to growth factors and
      nutrients and is a validated anticancer drug target. Rapamycin and related
      allosteric inhibitors of mTORC1 (mTOR complex 1) have had some success in
      specific tumour types, but have not exhibited broad anticancer activity,
      prompting the development of new ATP-competitive mTOR kinase inhibitors that
      inhibit both mTORC1 and mTORC2. In common with other targeted kinase inhibitors,
      tumours are likely to adapt and acquire resistance to mTOR inhibitors. In the
      present article, we review studies that describe how tumour cells adapt to become
      resistant to mTOR inhibitors. mTOR is a central signalling hub which responds to
      an array of signalling inputs and activates a range of downstream effector
      pathways. Understanding how this signalling network is remodelled and which
      pathways are invoked to sustain survival and proliferation in the presence of
      mTOR inhibitors can provide new insights into the importance of the various mTOR
      effector pathways and may suggest targets for intervention to combine with mTOR
      inhibitors. Finally, since chronic mTOR inhibition by rapamycin can increase
      lifespan and healthspan in nematodes, fruitflies and mice, we contrast these
      studies with tumour cell responses to mTOR inhibition. 

PMID- 23863164
TI  - WIPI beta-propellers in autophagy-related diseases and longevity.
AB  - Autophagy is a catabolic pathway in which the cell sequesters cytoplasmic
      material, including long-lived proteins, lipids and organelles, in specialized
      double-membrane vesicles, called autophagosomes. Subsequently, autophagosomes
      communicate with the lysosomal compartment and acquire acidic hydrolases for
      final cargo degradation. This process of partial self-eating secures the survival
      of eukaryotic cells during starvation periods and is critically regulated by
      mTORC1 (mammalian target of rapamycin complex 1). Under nutrient-poor conditions,
      inhibited mTORC1 permits localized PtdIns(3)P production at particular membranes
      that contribute to autophagosome formation. Members of the human WIPI (WD-repeat
      protein interacting with phosphoinositides) family fulfil an essential role as
      PtdIns(3)P effectors at the initiation step of autophagosome formation. In the
      present article, we discuss the role of human WIPIs in autophagy, and the
      identification of evolutionarily conserved amino acids of WIPI-1 that confer
      PtdIns(3)P binding downstream of mTORC1 inhibition. We also discuss the
      PtdIns(3)P effector function of WIPIs in the context of longevity and autophagy
      related human diseases, such as cancer and neurodegeneration. 

PMID- 23863165
TI  - Dawn of the dead: protein pseudokinases signal new adventures in cell biology.
AB  - Recent studies of proteins containing kinase-like domains that lack catalytic
      residue(s) classically required for phosphotransfer, termed pseudokinases, have
      uncovered important roles in cell signalling across the kingdoms of life.
      Additionally, mutations within pseudokinase domains are known to underlie human
      diseases, suggesting that these proteins may represent new and unexplored
      therapeutic targets. To date, few pseudokinases have been studied in intricate
      detail, but as described in the present article and in the subsequent papers in
      this issue of Biochemical Society Transactions, several new studies have provided
      an advanced template and an improved framework for interrogating the roles of
      pseudokinases in signal transduction. In the present article, we review landmarks
      in the establishment of this field of study, highlight some experimental
      challenges and propose a simple scheme for definition of these domains based on
      their primary sequences, rather than experimentally defined nucleotide-binding or
      catalytic activities. 

PMID- 23863166
TI  - Techniques to examine nucleotide binding by pseudokinases.
AB  - Approximately 10% of the human kinome has been classified as pseudokinases due to
      the absence of one or more of three motifs known to play key roles in the
      catalytic activities of protein kinases. Structural and functional studies are
      now emerging, reclassifying this 'dead' kinase family as essential signalling
      molecules that act as crucial modulators of signal transduction. This raises the
      prospect that pseudokinases may well represent an as-yet-unexplored class of drug
      targets. However, the extent to which nucleotide binding and catalytic activity
      contribute to the biological functions of pseudokinases remains an area of great
      controversy. In the present review, we discuss the advantages and disadvantages
      of the different methods employed to characterize the nucleotide-binding
      properties and activity of pseudokinases. 

PMID- 23863168
TI  - A pickup in pseudokinase activity.
AB  - Kinases catalyse the phosphorylation of target substrates on hydroxy group
      containing residues as a means to nucleate multi-component complexes or to
      stabilize unique conformational states. Through this biochemical activity,
      kinases play critical roles in many signal transduction and disease pathways.
      Pseudokinases constitute a subclass of these enzymes that were originally
      predicted as inactive on the basis of mutations of key conserved active-site
      residues. However, recent biochemical and structural analyses have revealed
      several enzymatically active pseudokinases, suggesting either that novel
      mechanisms of phosphorylation are at play or that the constraints for highly
      conserved active-site residues are looser than originally anticipated. The
      purpose of the present review is to summarize several of the active
      pseudokinases, and one in particular termed KSR (kinase suppressor of Ras), which
      was recently found to possess a kinase activity that can become accelerated
      through an allosteric mechanism. Utilization of catalytic activity or structural
      features of the kinase fold may be key to the function of many pseudokinases. 

PMID- 23863167
TI  - Pseudokinases from a structural perspective.
AB  - The catalytic (C) subunit of PKA was the first protein kinase structure to be
      solved, and it continues to serve as the prototype for the protein kinase
      superfamily. In contrast, by comparing many active and inactive kinases, we
      developed a novel 'spine' concept where every active kinase is composed of two
      hydrophobic spines anchored to a hydrophobic F-helix. The R-spine (regulatory
      spine) is dynamically assembled, typically by activation loop phosphorylation,
      whereas the C-spine (catalytic spine) is completed by the adenine ring of ATP. In
      the present paper, we show how the spine concept can be applied to B-Raf,
      specifically to engineer a kinase-dead pseudokinase. To achieve this, we mutated
      one of the C-spine residues in the N-lobe (N-terminal lobe), Ala481, to
      phenylalanine. This mutant cannot bind ATP and is thus kinase-dead, presumably
      because the phenylalanine ring fills the adenine-binding pocket. The C-spine is
      thus fused. However, the A481F mutant is still capable of binding wild-type B-Raf
      and wild-type C-Raf, and dimerization with a wild-type Raf leads to downstream
      activation of MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular
      signal-regulated kinase) kinase] and ERK. The mutant requires dimerization, but
      is independent of Ras and does not require enzymatic activity. By distinguishing
      between catalytic and scaffold functions of B-Raf, we define kinases as being
      bifunctional and show that, at least in some cases, the scaffold function is
      sufficient for downstream signalling. Since this alanine residue is one of the
      most highly conserved residues in the kinome, we suggest that this may be a
      general strategy for engineering kinase-dead pseudokinases and exploring
      biological functions that are independent of catalysis. 

PMID- 23863169
TI  - ILK: a pseudokinase with a unique function in the integrin-actin linkage.
AB  - ILK (integrin-linked kinase) is a central component of cell-matrix adhesions and
      an important regulator of integrin function. It forms a ternary complex with two
      other adaptor proteins, PINCH (particularly interesting cysteine- and histidine
      rich protein) and parvin, forming the IPP (ILK-PINCH-parvin) complex that
      regulates the integrin-actin linkage as well as microtubule dynamics. These
      functions are essential for processes such as cell migration and matrix
      remodelling. The present review discusses the recent advances on the structural
      and functional characterization of ILK and the long-standing debate regarding its
      reported kinase activity. 

PMID- 23863170
TI  - New insights into the structure and function of the pseudokinase domain in JAK2.
AB  - JAK (Janus kinase) 2 plays a critical role in signal transduction through several
      cytokine receptors. JAKs contain a typical tyrosine kinase domain preceded by a
      pseudokinase [JH2 (JAK homology 2)] domain which has been considered to be
      catalytically inactive. Identification of activating mutations in the JH2 domain
      of JAK2 as the major cause for polycythaemia vera and other MPNs
      (myeloproliferative neoplasms) demonstrate the critical regulatory function for
      this domain, but the underlying mechanisms have remained elusive. We have
      performed biochemical and functional analysis on the JH2 domain of JAK2. The
      results indicate that JH2 functions as an active protein kinase and
      phosphorylates two residues in JAK2 (Ser523 and Tyr570) that have been shown
      previously to be negative regulatory sites for JAK2 activity. The crystal
      structure of the JAK2 JH2 domain provides an explanation for the functional
      findings and shows that JH2 adopts a prototypical kinase fold, but binds MgATP
      through a non-canonical mode. The structure of the most prevalent pathogenic JH2
      mutation V617F shows a high level of similarity to wild-type JH2. The most
      notable structural deviation is observed in the N-lobe alphaC-helix. The
      structural and biochemical data together with MD (molecular dynamics) simulations
      show that the V617F mutation rigidifies the alphaC-helix, which results in
      hyperactivation of the JH1 domain through an as yet unidentified mechanism. These
      results provide structural and functional insights into the normal and pathogenic
      function of the JH2 domain of JAK2. 

PMID- 23863171
TI  - Structural characterization of the cyclin-dependent protein kinase family.
AB  - Structural studies of members of the CDK (cyclin-dependent protein kinase) family
      have made a significant contribution to our understanding of the regulation of
      protein kinases. The structure of monomeric unphosphorylated CDK2 was the first
      of an inactive protein kinase to be determined and, since then, structures of
      other members of the CDK family, alone, in complex with regulatory proteins and
      in differing phosphorylation states, have enhanced our understanding of the
      molecular mechanisms regulating protein kinase activity. Recently, our knowledge
      of the structural biology of the CDK family has been extended by determination of
      structures for members of the transcriptional CDK and CDK-like kinase branches of
      the extended family. We include these recent structures in the present review and
      consider them in the light of current models for CDK activation and regulation. 

PMID- 23863172
TI  - Structural constraints and functional divergences in CASK evolution.
AB  - CASK (Ca2+/calmodulin-activated serine kinase) is a synaptic protein that
      interacts with the cytosolic tail of adhesion molecules such as neurexins, syncam
      and syndecans. It belongs to the MAGUK (membrane-associated guanylate kinase)
      family of scaffolding proteins which are known to decorate cell-cell junctions.
      CASK is an essential gene in mammals, critical for neurodevelopment. Mutations in
      the CASK gene in humans result in phenotypes that range from intellectual
      disability to lethality. Despite its importance, CASK has a single genetic
      isoform located in the short arm of the X chromosome near an evolutionary
      breakpoint. Surprisingly, CASK is a non-essential gene in invertebrates and
      displays functional divergence. In the present article, we describe the
      phylogenetic differences in existing CASK orthologues. The CASK gene has
      undergone a huge expansion in size (~55-fold). Almost all of this expansion is a
      direct result of an increase in the size of the introns. The coding region of
      CASK orthologues, and hence the protein, exhibit a high degree of evolutionary
      conservation. Within the protein, domain arrangement is completely conserved and
      substitution rates are higher in the connecting loop regions [L27 (Lin2, Lin7)]
      than within the domain. Our analyses of single residue substitutions and genotype
      phenotype relationships suggest that, other than intronic expansion, the dramatic
      functional changes of CASK are driven by subtle (non-radical) primary structure
      changes within the CASK protein and concomitant changes in its protein
      interactors. 

PMID- 23863173
TI  - Histidine kinases from bacteria to humans.
AB  - It is more than 50 years since protein histidine phosphorylation was first
      discovered in 1962 by Boyer and co-workers; however, histidine kinases are still
      much less well recognized than the serine/threonine and tyrosine kinases. The
      best-known histidine kinases are the two-component signalling kinases that occur
      in bacteria, fungi and plants. The mechanisms and functions of these kinases,
      their cognate response regulators and associated phosphorelay proteins are
      becoming increasingly well understood. When genomes of higher eukaryotes began to
      be sequenced, it did not appear that they contained two-component histidine
      kinase system homologues, apart from a couple of related mitochondrial enzymes
      that were later shown not to function as histidine kinases. However, as a result
      of the burgeoning sequencing of genomes from a wide variety of eukaryotic
      organisms, it is clear that there are proteins that correspond to components of
      the two-component histidine kinase systems in higher eukaryotes and that
      operational two-component kinase systems are likely to occur in these organisms.
      There is unequivocal direct evidence that protein histidine phosphorylation does
      occur in mammals. So far, only nucleoside diphosphate kinases have been shown to
      be involved in protein histidine phosphorylation, but their mechanisms of action
      are not well understood. It is clear that other, yet to be identified, histidine
      kinases also exist in mammals and that protein histidine phosphorylation may play
      important roles in higher eukaryotes. 

PMID- 23863175
TI  - The structural mechanisms that underpin mitotic kinase activation.
AB  - In eukaryotic cells, the peak of protein phosphorylation occurs during mitosis,
      switching the activities of a significant proportion of proteins and
      orchestrating a wholesale reorganization of cell shape and internal architecture.
      Most mitotic protein phosphorylation events are catalysed by a small subset of
      serine/threonine protein kinases. These include members of the Cdk (cyclin
      dependent kinase), Plk (Polo-like kinase), Aurora, Nek (NimA-related kinase) and
      Bub families, as well as Haspin, Greatwall and Mps1/TTK. There has been steady
      progress in resolving the structural mechanisms that regulate the catalytic
      activities of these mitotic kinases. From structural and biochemical
      perspectives, kinase activation appears not as a binary process (from inactive to
      active), but as a series of states that exhibit varying degrees of activity. In
      its lowest activity state, a mitotic kinase may exhibit diverse autoinhibited or
      inactive conformations. Kinase activation proceeds via phosphorylation and/or
      association with a binding partner. These remodel the structure into an active
      conformation that is common to almost all protein kinases. However, all mitotic
      kinases of known structure have divergent features, many of which are key to
      understanding their specific regulatory mechanisms. Finally, mitotic kinases are
      an important class of drug target, and their structural characterization has
      facilitated the rational design of chemical inhibitors. 

PMID- 23863174
TI  - Receptor tyrosine kinases with intracellular pseudokinase domains.
AB  - As with other groups of protein kinases, approximately 10% of the RTKs (receptor
      tyrosine kinases) in the human proteome contain intracellular pseudokinases that
      lack one or more conserved catalytically important residues. These include ErbB3,
      a member of the EGFR (epidermal growth factor receptor) family, and a series of
      unconventional Wnt receptors. We showed previously that, despite its reputation
      as a pseudokinase, the ErbB3 TKD (tyrosine kinase domain) does retain
      significant, albeit weak, kinase activity. This led us to suggest that a subgroup
      of RTKs may be able to signal even with very inefficient kinases. Recent work
      suggests that this is not the case, however. Other pseudokinase RTKs have not
      revealed significant kinase activity, and mutations that impair ErbB3's weak
      kinase activity have not so far been found to exhibit signalling defects. These
      findings therefore point to models in which the TKDs of pseudokinase RTKs
      participate in receptor signalling by allosterically regulating associated
      kinases (such as ErbB3 regulation of ErbB2) and/or function as regulated
      'scaffolds' for other intermolecular interactions central to signal propagation.
      Further structural and functional studies, particularly of the pseudokinase RTKs
      involved in Wnt signalling, are required to shed new light on these intriguing
      signalling mechanisms. 

PMID- 23863176
TI  - Regulation of Janus kinases by SOCS proteins.
AB  - JAKs (Janus kinases) are essential mediators of almost all biological signalling
      events initiated by haemopoietic and immune cytokines. However, aberrant and/or
      prolonged JAK-induced signalling is detrimental and can give rise to a number of
      inflammatory and proliferative pathologies. For this reason, the tyrosine kinase
      activity of the JAKs is carefully regulated at a number of different levels.
      Primarily, this is achieved by: (i) ensuring that the catalytic domain is
      'switched off' under basal conditions, and (ii) inhibiting the activity of JAK
      after it has been switched on. Whereas the first mode of inhibition is mediated
      by JAK's own pseudokinase domain as well as the action of phosphatases, the
      second is achieved by the action of the SOCS (suppressor of cytokine signalling)
      proteins, negative-feedback inhibitors of JAK-mediated signalling. The present
      review focuses on the mode of action of SOCS1 and SOCS3, the two most potent JAK
      inhibitors. 

PMID- 23863177
TI  - Activating Janus kinase pseudokinase domain mutations in myeloproliferative and
      other blood cancers.
AB  - The discovery of the highly prevalent activating JAK (Janus kinase) 2 V617F
      mutation in myeloproliferative neoplasms, and of other pseudokinase domain
      activating mutations in JAK2, JAK1 and JAK3 in blood cancers, prompted great
      interest in understanding how pseudokinase domains regulate kinase domains in
      JAKs. Recent functional and mutagenesis studies identified residues required for
      the V617F mutation to induce activation. Several X-ray crystal structures of
      either kinase or pseudokinase domains including the V617F mutant of JAK2
      pseudokinase domains are now available, and a picture has emerged whereby the
      V617F mutation induces a defined conformational change around helix C of JH (JAK
      homology) 2. Effects of mutations on JAK2 can be extrapolated to JAK1 and TYK2
      (tyrosine kinase 2), whereas JAK3 appears to be different. More structural
      information of the full-length JAK coupled to cytokine receptors might be
      required in order to define the structural basis of JH1 activation by JH2 mutants
      and eventually obtain mutant-specific inhibitors. 

PMID- 23863178
TI  - Nuclear receptor-binding protein 1: a novel tumour suppressor and pseudokinase.
AB  - Pseudokinases are a class of kinases which are structurally designated as lacking
      kinase activity. Despite the lack of kinase domain sequence conservation, there
      is increasing evidence that a number of pseudokinases retain kinase activity
      and/or have critical cellular functions, casting aside previous notions that
      pseudokinases simply exist as redundant kinases. Moreover, a number of recent
      studies have implicated pseudokinases as critical components in cancer formation
      and progression. The present review discusses the interactions and potential
      functions that nuclear receptor-binding protein 1, a pseudokinase recently
      described to have a tumour-suppressive role in cancer, may play in cellular
      homoeostasis and protein regulation. The recent findings highlighted in the
      present review emphasize the requirement to fully determine the function of
      pseudokinases in vitro and in vivo, the understanding of which may ultimately
      uncover new directions for drug discovery. 

PMID- 23863179
TI  - Phosphorylation of substrates destined for secretion by the Fam20 kinases.
AB  - Since the discovery of protein kinases, protein phosphorylation has emerged as a
      key regulatory mechanism. The majority of phosphoproteins reside within the
      nucleus and cytoplasm; however, many secreted proteins are phosphorylated by
      unknown kinases located within the secretory pathway and/or in the extracellular
      space. The Fam20 kinases are emerging as the enzymes responsible for
      phosphorylating secreted proteins and proteoglycans. Evolutionary analysis
      reveals that these kinases are exclusively present in metazoans and contain
      conserved features that are common among all eukaryotic protein kinases.
      Mutations in the Fam20 family members cause disorders of biomineralization in
      humans that highlight the physiological significance of secreted protein
      phosphorylation. 

PMID- 23863180
TI  - Mechanistic and functional diversity in the mechanosensory kinases of the titin
      like family.
AB  - The giant cytoskeletal kinases of the titin-like family are emerging as key
      mediators of stretch-sensing in muscle. It is thought that their elastic
      conformational deformation during muscle function regulates both their catalysis
      and the recruitment of regulatory proteins to signalosomes that assemble in their
      vicinity. In the present article, we discuss the speciation of mechanosensory
      mechanisms in titin-like kinases, their scaffolding properties and the
      kinase/pseudokinase domain variations that define a rich functional diversity
      across the family. 

PMID- 23863181
TI  - Prospects for stable analogues of phosphohistidine.
AB  - Phosphorylation is a ubiquitous protein post-translational modification, and the
      importance of phosphorylation of serine, threonine and tyrosine is well
      established. What is lesser known is that almost all heteroatom-containing amino
      acids can be phosphorylated and, among these, histidine, aspartate and cysteine
      have well established roles in bacterial signalling pathways. The first of these,
      phosphohistidine, is the most unusual in that it is labile under many conditions
      used to study proteins in vitro and can exist as two different isomers. In the
      present short review, we highlight the chemical challenges that this modification
      presents and the manner in which chemical synthesis has been used to identify and
      mimic the modification in proteins. 

PMID- 23863182
TI  - The dual function of KSR1: a pseudokinase and beyond.
AB  - Protein kinases play a pivotal role in regulating many aspects of biological
      processes, including development, differentiation and cell death. Within the
      kinome, 48 kinases (~10%) are classified as pseudokinases owing to the fact that
      they lack at least one conserved catalytic residue in their kinase domain.
      However, emerging evidence suggest that some pseudokinases, even without the
      ability to phosphorylate substrates, are regulators of multiple cellular
      signalling pathways. Among these is KSR1 (kinase suppressor of Ras 1), which was
      initially identified as a novel kinase in the Ras/Raf pathway. Subsequent studies
      showed that KSR1 mainly functions as a platform to assemble different cellular
      components thereby facilitating signal transduction. In the present article, we
      discuss recent findings regarding KSR1, indicating that it has dual activity as
      an active kinase as well as a pseudokinase/scaffolding protein. Moreover, the
      biological functions of KSR1 in human disorders, notably in malignancies, are
      also reviewed. 

PMID- 23863183
TI  - Pseudokinase drug intervention: a potentially poisoned chalice.
AB  - Pseudokinases, the catalytically impaired component of the kinome, have recently
      been found to share more properties with active kinases than previously thought.
      In many pseudokinases, ATP binding and even some activity is preserved,
      highlighting these proteins as potential drug targets. In both active kinases and
      pseudokinases, binding of ATP or drugs in the nucleotide-binding pocket can
      stabilize specific conformations required for activity and protein-protein
      interactions. We discuss the implications of locking particular conformations in
      a selection of (pseudo)kinases and the dual potential impact on the druggability
      of these proteins. 

PMID- 23863184
TI  - Attempting to rewrite History: challenges with the analysis of histidine
      phosphorylated peptides.
AB  - A significant number of proteins in both eukaryotes and prokaryotes are known to
      be post-translationally modified by the addition of phosphate, serving as a means
      of rapidly regulating protein function. Phosphorylation of the amino acids
      serine, threonine and tyrosine are the focus of the vast majority of studies
      aimed at elucidating the extent and roles of such modification, yet other amino
      acids, including histidine and aspartate, are also phosphorylated. Although
      histidine phosphorylation is known to play extensive roles in signalling in
      eukaryotes, plants and fungi, roles for phosphohistidine are poorly defined in
      higher eukaryotes. Characterization of histidine phosphorylation aimed at
      elucidating such information is problematic due to the acid-labile nature of the
      phosphoramidate bond, essential for many of its biological functions. Although MS
      based strategies have proven extremely useful in the analysis of other types of
      phosphorylated peptides, the chromatographic procedures essential for such
      approaches promote rapid hydrolysis of phosphohistidine-containing peptides.
      Phosphate transfer to non-biologically relevant aspartate residues during MS
      analysis further complicates the scenario. 

PMID- 23863185
TI  - The functionally diverse roles of tribbles.
AB  - Tribbles are members of the pseudokinase family of proteins, with no associated
      kinase activity detectable to date. As tribbles appear not to function as
      kinases, there has been debate surrounding their functional classification.
      Tribbles have been proposed to function as adaptor molecules facilitating
      degradation of their target proteins. Tribbles have also been proposed to mediate
      signalling changes to MAPK (mitogen-activated protein kinase) cascades and also
      to function as decoy kinases interfering with the activity of known kinases. The
      present review discusses the functionally divergent roles of tribbles as
      molecular adaptors mediating degradation, changes to signalling cascades and
      action as decoy kinases. 

PMID- 23863187
TI  - Hyperbaric oxygen therapy for diabetic ulcers: systematic review and meta
      analysis.
AB  - OBJECTIVES: Approximately 10-15 percent of individuals with diabetes mellitus
      develop foot ulcers, which precede 85 percent of amputations. Increased oxygen,
      through the use of hyperbaric oxygen therapy (HBOT), has been suggested to
      encourage ulcer healing thus reducing the risk of amputation. The objective of
      this systematic review is to evaluate the efficacy of systemic HBOT for
      nonhealing ulcers of the lower limb in diabetes patients. METHODS: A systematic
      search, using controlled and keyword terms focusing on "HBOT" and "lower limb
      diabetic ulcers," was conducted. Databases searched included Medline, EMBASE,
      CINAHL, PubMed, Wiley's Cochrane Library, and Biosis. Randomized controlled
      trials (RCTs) and observational studies were included. Pooled estimates of
      outcomes were determined when appropriate. RESULTS: Of the 654 citations
      identified, 157 articles underwent full-text review. Data were abstracted from
      twelve publications (six RCTs and six comparative observational studies). Pooled
      analysis of the RCT and observational data showed that treatment with HBOT
      reduced the risk of major amputation by 60 percent (p = .29) and 61 percent (p =
      .003) compared with standard wound care, respectively. The RCT data revealed that
      the relative risk of having an unhealed wound following HBOT was 0.54 (p = .10)
      and 0.24 (p < .0001) based on observational data. CONCLUSIONS: Due to the limited
      RCT evidence, it is not possible to conclusively establish the benefits and harms
      of treating diabetic lower limb ulcers with HBOT. No significant effects on
      amputation rates were found in the RCT evidence and in the high quality studies,
      no difference was found.

PMID- 23863188
TI  - Assessing the impacts of citizen deliberations on the health technology process.
AB  - OBJECTIVES: We assessed the impacts of a Citizens' Reference Panel on the
      deliberations of a provincial health technology advisory committee and its
      secretariat, which produce, recommendations for the use of health technologies in
      Ontario, Canada. METHODS: A fourteen-member citizens' reference panel was
      convened five times between February 2009 and May 2010 to participate in
      informed, facilitated discussions to inform the assessment of individual
      technologies and provincial health technology assessment processes more
      generally. Qualitative data collection methods were used to document observed and
      perceived impacts of the citizens' panel on the health technology assessment
      (HTA) process. RESULTS: Panel impacts were observed for all technologies
      reviewed, at two different stages in the HTA process, and represented macro-
      (raising awareness) and micro-level (informing recommendations) impacts. These
      impacts were shaped by periodic opportunities for direct and brokered exchange
      between the Panel and the expert advisory committee to clarify roles, foster
      accountability, and build trust. Our findings offer new insights about one of the
      main considerations in the design of deliberative participatory structures-how to
      maintain the independence of a citizens' panel while ensuring that their input is
      considered at key junctures in the HTA process. CONCLUSIONS: Citizens' panels can
      exert various impacts on the HTA process. Ensuring these types of structures
      include opportunities for direct exchange between citizens and experts, to
      clarify roles, promote accountability, and build trust will facilitate their
      impacts in a variety of settings.

PMID- 23863189
TI  - Quantitative patient preference evidence for health technology assessment: a case
      study.
AB  - OBJECTIVES: We conducted a systematic review of quantitative research regarding
      patients' preferences, perspectives and values for ventilation among chronic
      obstructive pulmonary disease (COPD) patients. Our objective was to explore the
      feasibility and desirability of incorporating patient preferences within the
      health technology assessment (HTA) process by working through a case study.
      METHODS: Medical and economic databases were searched for studies published in
      English from 1990 through March 4, 2011. Studies were selected based on title and
      abstract. Due to the heterogeneity of the studies, data were analyzed using a
      narrative synthesis approach. RESULTS: Among 1833 identified citations, twelve
      studies met our inclusion criteria. Ten of these studies pertained to COPD
      patient preferences for ventilation. Results indicate that a significant
      proportion of COPD patients are willing to forgo ventilation, particularly when
      it is expressed as "indefinite life support" (60-78 percent) rather than as
      temporary modality. Results indicate that patient preferences for mechanical or
      noninvasive ventilation cannot be predicted by covariates (e.g., age, quality of
      life) or by others who are frequently called upon to make decisions are their
      behalf. CONCLUSIONS: We found that it is indeed feasible to conduct a systematic
      review of quantitative preference-related evidence for an HTA topic. However, the
      process of conducting this preference-related case study also revealed several
      challenges because there is a high degree of variation in taxonomy,
      instrumentation, and study design. Therefore, we do not recommend it as a routine
      part of the HTA process, but we suggest that it is a promising area to pursue for
      preference-sensitive technological decisions.

PMID- 23863190
TI  - Factors influencing decision making on therapeutic interventions.
AB  - OBJECTIVES: The aim of this study was to explore factors that influenced decision
      making in the assessment of new health technology in Korea. METHODS: We analyzed
      the decision-making results of the Committee for New Health Technology Assessment
      (CnHTA) on fifty-three new nondrug health technologies in Korea from July 2007 to
      December 2010. The scope of the committee was mainly limited to safety and
      efficacy/effectiveness, and every decision was based on a systematic review of
      the literature. The committee was composed of healthcare professionals, policy
      makers, lawyers, and representatives from nongovernmental organizations.
      Decisions made on therapeutic interventions were included, while those on
      diagnostic procedures were excluded. RESULTS: Factors that positively influenced
      decisions were lower complication rate than existing technology, similar or
      greater effectiveness compared with existing technology, ability to save critical
      organs, absence of alternative intervention, decreased invasiveness, expansion of
      patient's set of choices, and similarity to the mechanism of existing technology.
      Factors that negatively influenced decisions were higher complication rates than
      existing technology, lower effectiveness than comparable technology, low levels
      of evidence, unknown mechanisms of intervention, inconsistency, lack of long-term
      outcomes, lack of comparative data, nonstandardized technology, heterogeneity
      between control and treatment, excessively diverse indications, and
      nongeneralizability. CONCLUSIONS: This qualitative analysis of past decision
      making results provided us with clues on the values that decision makers on the
      Korean CnHTA considered in terms of safety and effectiveness. These findings will
      help us develop appraisal guidelines and enhance the objectivity of decision
      making processes in Korea.

PMID- 23863191
TI  - Use of implicit and explicit bayesian methods in health technology assessment.
AB  - OBJECTIVES: The aim of this study was to examine the use of implicit and explicit
      Bayesian methods in health technology assessments and to identify whether this
      has changed over time. METHODS: A review of all health technology assessment
      (HTA) reports of secondary research published by the UK National Institute of
      Health Research (NIHR) between 1997 and 2011. Data were extracted on the use and
      implementation of Bayesian methods, whether defined as such by the original
      authors (i.e., explicit) or not (i.e., implicit). RESULTS: A total of 155 of 375
      (41 percent) NIHR HTA reports, identified as relevant to this review, contained a
      Bayesian analysis. Of these, 128 (83 percent) contained an implicit Bayesian
      analysis, 3 (2 percent) an explicit Bayesian analysis and 24 (15 percent) both
      implicit and explicit Bayesian analyses. Of the twenty-seven reports that
      explicitly used Bayes theorem, only six included prior information in the form of
      (informative) prior distributions. Over time, the percentage of HTA reports that
      used Bayesian (implicit and/or explicit) methods increased from 0 percent in 1997
      to nearly 80 percent in 2011. CONCLUSIONS: This review has shown that there has
      been an increase in the use of Bayesian methods in HTA, which is likely to be a
      result of the increase in freely available resources to implement the approach.
      Areas where Bayesian methods have the potential to advance healthcare evaluations
      in the future are considered in the discussion.

PMID- 23863192
TI  - Effects of running wheel training on adult obese rats programmed by maternal
      prolactin inhibition.
AB  - The inhibition of maternal prolactin production in late lactation leads to
      metabolic syndrome and hypothyroidism in adult offspring. Physical training is a
      therapeutic strategy that could prevent or reverse this condition. We evaluated
      the effects of a short-duration low-intensity running wheel training program on
      the metabolic and hormonal alterations in rats. Lactating Wistar rats were
      treated with bromocriptine (Bro, 1 mg twice a day) or saline on days 19, 20, and
      21 of lactation, and the training of offspring began at 35 days of age. Offspring
      were divided into sedentary and trained controls (C-Sed and C-Ex) and sedentary
      and trained Bro-treated rats (Bro-Sed and Bro-Ex). Chronic exercise delayed the
      onset of weight gain in Bro-Ex offspring, and the food intake did not change
      during the experimental period. At 180 days, visceral fat mass was higher (+46%)
      in the Bro-Sed offspring than in C-Sed and Bro-Ex rats. As expected, running
      capacity was higher in trained animals. Most parameters observed in the Bro-Sed
      offspring were consistent with hypothyroidism and metabolic syndrome and were
      reversed in the Bro-Ex group. Chronic exercise did not influence the muscle
      glycogen in the C-Ex group; however, liver glycogen was higher (+30%) in C-Ex
      group and was unchanged in both Bro offspring groups. Bro-Ex animals had higher
      plasma lactate dehydrogenase levels, indicating skeletal muscle damage and
      intolerance of the training program. Low-intensity chronic training is able to
      normalize many clinical aspects in Bro animals; however, these animals might have
      had a lower threshold for exercise adaptation than the control rats. 

PMID- 23863193
TI  - Near-UV circular dichroism and UV resonance Raman spectra of tryptophan residues
      as a structural marker of proteins.
AB  - Near-UV circular dichroism (CD) and UV resonance Raman (UVRR) spectra of L
      tryptophan (Trp), its derivatives, and indole-C3 derivatives were investigated to
      utilize Trp signals of proteins as a structural marker. CD spectra of Trp are
      classified into four types: Free L-Trp gives type II (around 270 nm, L(a)
      transition), while L-Trp in proteins generally yields type I (around 280-290 nm,
      L(b) transition) often with vibronic structures. All the indole-C3 derivatives
      except for L-Trp gave no CD bands for L(a) and L(b) transitions, indicating that
      the asymmetric carbon (Calpha) connected through C3-Cbeta is essential to
      appearance of CD. We demonstrate here that the type of CD spectra is determined
      by a condition of the amino group of Trp; it was changed from type II to type I
      by the modification of the amino group. In contrast, the modification of the
      carboxyl group of L-Trp had little effects on a CD spectrum. The 229 nm excited
      UVRR spectra were almost the same between L-Trp and indole-C3 derivatives.
      Comparison of CD and UVRR spectra of Trp residues in proteins suggested that
      mainly the W17 (possibly together with W16) mode contributes to the
      characteristic vibronic coupling of L(b) transition. Both UVRR and CD spectra of
      L-Trp were influenced by protonation of amino and/or carboxyl groups, but those
      changes were distinguished from hydrogen bonding effects at N1H of indole. It is
      likely that these protonations are communicated to indole through sigma-bonds
      containing Calpha and thus influence both chirality of L(a) and L(b) transitions
      and properties of the Bb excited state.

PMID- 23863194
TI  - The effect of diesters and lauric acid on rheological properties of air/water
      interfaces stabilized by oligofructose lauric acid monoesters.
AB  - In this study, the rheological properties of interfaces stabilized by
      oligofructose fatty acid esters were elucidated. First, the properties of
      interfaces stabilized by monoesters (ME), diesters (DE), lauric acid (LA),
      oligofructose (OF), and mixtures of ME with DE, LA, or OF were studied. Second,
      the properties of interfaces stabilized by the crude product (CP) containing ME,
      DE, LA, and OF were studied. The dependency of the dilatational modulus on
      frequency and deformation amplitude indicated the possible formation of a soft
      glass phase for ME, and a viscous interface for DE. When ME and DE were mixed at
      a ratio of 0.8/0.2, the experimental results suggest that the interfacial
      structure consists of islands of a glass phase formed by ME, dispersed in a 2D
      viscous phase of DE. CP stabilized interfaces, where the ratio ME/DE was higher,
      lead to a different rheological response. The ratio ME/DE plays an important role
      in the surface properties of the CP. This may have significant consequences for
      applications in macroscopic systems such as foams. 

PMID- 23863195
TI  - Tooth tissue engineering: the influence of hydrophilic surface on nanocrystalline
      diamond films for human dental stem cells.
AB  - New techniques for tissue engineering (TE) are rapidly emerging. The basic
      concept of autologous TE is to isolate cells from small biopsy specimens, and to
      expand these cells in culture for subsequent seeding onto biodegradable
      scaffolds. Nanocrystalline diamond films have attracted the attention of
      researchers from a variety of different areas in recent years, due to their
      unique and exceptional properties. In this approach, human dental stem cells
      (hDSCs) were characterized by flow cytometry and grown on diamond films with
      hydrogen (H)-terminated and oxygen (O)-terminated surfaces for 28 days, and then
      removed by lysis and washing with distilled water. Energy dispersive spectroscopy
      analysis was performed, showing that the regions with O-terminated surfaces
      contained much higher levels of deposited calcium, oxygen, and phosphorus. These
      results suggest that the extracellular matrix was considerably more developed in
      the O-terminated regions, as compared with the H-terminated regions. In addition,
      optical microscopy of hDSCs cultured on the diamond substrate with H- and O
      terminated surfaces, before washing with distilled water, showed preferential
      directions of the cells arrangement, where orthogonal lines suggest that the
      cells appeared to be following the O-terminated regions or hydrophilic surface.
      These findings suggest that O-terminated diamond surfaces prepared on
      biodegradable scaffolds can be useful for mineralized dental tissue formation. 

PMID- 23863196
TI  - Rehabilitation outcome following war-related transtibial amputation in Kosovo.
AB  - BACKGROUND: Previous literature has suggested that age, level of amputation,
      residual limb length, comorbidities, mental disorders, and cause of amputation
      can affect the ability to successfully ambulate with prosthesis. OBJECTIVES: The
      objective of this study was to analyze the predictors that affect the
      rehabilitation outcome of war-related transtibial amputees and the relationship
      of these factors with ambulation ability after prosthetic fitting. STUDY DESIGN:
      Retrospective observational study. METHODS: We reviewed the records of 69 war
      related transtibial amputees. The rehabilitation outcome was analyzed according
      to the grade of rehabilitation summarized in three grades. Multiple logistic
      regression analysis was used to determine the odds of achieving the first
      rehabilitation grade. RESULTS: The majority of patients with transtibial
      amputations achieved the first grade of rehabilitation (59.4%). The factors that
      significantly influenced the achievement of the first grade of rehabilitation
      were age and absence of posttraumatic stress disorder. For every 1-year increase
      in patient age, the odds of achieving first grade of rehabilitation decreased by
      a factor of 0.9. Patients without posttraumatic stress disorder had 12.9 greater
      odds of achieving the first rehabilitation grade compared to patients with
      posttraumatic stress disorder. CONCLUSION: Achievement of the first grade of
      rehabilitation among war-related transtibial amputees is dependent on patient age
      and the absence of posttraumatic stress disorder. CLINICAL RELEVANCE:
      Understanding the factors that may affect the rehabilitation outcome of war
      related amputees could lead to a more specific organization of the
      rehabilitation, especially in a country that has recently been involved in war.
      This is the first study to focus on determinants of prosthetic rehabilitation in
      these patients.

PMID- 23863197
TI  - Inhibition of endothelial nitric oxide synthase induces and enhances myocardial
      fibrosis.
AB  - AIMS: The endothelial nitric oxide synthase (eNOS) contributes to cardiac
      remodelling. We studied the role of eNOS in the development of myocardial
      fibrosis during cardiac overload. METHODS AND RESULTS: Ten-week-old male C57/Bl6
      wildtype (WT) and eNOS mice (eNOS(-/-)) were subjected to transverse aortic
      constriction (TAC, 360 MUm) and WT were treated with L-N(G)-nitroarginine methyl
      ester (L-NAME, 100 mg/kg/day) for 35 days. Inhibition of eNOS by L-NAME induced
      interstitial fibrosis, augmented replacement fibrosis, and induced apoptosis of
      cardiac fibroblasts and cardiomyocytes. L-NAME and eNOS(-/-) markedly increased
      the fibrosis induced by TAC and enhanced the myocardial prevalence of CXCR4(pos)
      fibroblasts. Myocardial stromal-derived factor-1 (SDF-1) expression was up
      regulated by l-NAME and down-regulated after TAC. Blood pressure lowering by co
      treatment with hydralazine (250 mg/L/day) did not reverse the L-NAME effects. In
      mice transplanted with green fluorescent protein (GFP)(pos) bone marrow, L-NAME
      increased the percentage of GFP(pos) fibroblasts in the myocardium to 45-70%.
      Strain-mismatched BMT of eNOS(-/-)-BM increased and of WT-BM decreased the
      percentage of CXCR4(pos) fibroblasts in all groups. The number of fibrocytes
      (CD45(pos) collagen I(pos) cells) in the peripheral blood and in the bone marrow
      was increased both by TAC and L-NAME. L-NAME but not the inhibitor of inducible
      NOS 1400 W and of neuronal NOS 7-nitroindazole increased hydroxyproline and
      collagen Ialpha1. L-NAME up-regulated SDF-1 mRNA in cultured neonatal rat cardiac
      fibroblasts as well as their migratory capacity. CONCLUSION: eNOS inhibition
      induces and enhances cardiac fibrosis independently of blood pressure by
      activating SDF-1/CXCR4, extracellular matrix production in cardiac fibroblasts
      and by increasing recruitment of fibrocytes from the bone marrow.

PMID- 23863199
TI  - Divergent RNA transcription: a role in promoter unwinding?
AB  - New approaches using biotinylated-psoralen as a probe for investigating DNA
      structure have revealed new insights into the relationship between DNA
      supercoiling, transcription and chromatin compaction. We explore a hypothesis
      that divergent RNA transcription generates negative supercoiling at promoters
      facilitating initiation complex formation and subsequent promoter clearance. 

PMID- 23863198
TI  - Non-canonical activity of retinoic acid in epigenetic control of embryonic stem
      cell.
AB  - Non-canonical cytoplasmic activities and signal transduction of retinoic acid
      (RA) expand RA's pleiotropic effects in coordinating the epigenome in embryonic
      stem cell (ESC). Examples include RA-bound cellular retinoic acid binding protein
      I, which activates ERK2. By engaging both cytosolic and nuclear mediators, RA can
      efficiently augment ESC's epigenome. 

PMID- 23863200
TI  - Transcriptional changes induced by the tumor dormancy-associated microRNA-190.
AB  - Tumor dormancy is a highly prevalent stage in cancer progression. We have
      previously generated and characterized in vivo experimental models of human tumor
      dormancy in which micro-tumors remain occult until they spontaneously shift into
      rapid tumor growth. We showed that the dormant micro-tumors undergo a stable
      microRNA (miRNA) switch during their transition from dormancy to a fast-growing
      phenotype and reported the identification of a consensus signature of human tumor
      dormancy-associated miRNAs (DmiRs). miRNA-190 (miR-190) is among the most
      upregulated DmiRs in all dormant tumors analyzed. Upregulation of miR-190 led to
      prolonged tumor dormancy in otherwise fast-growing glioblastomas and
      osteosarcomas. Here we investigate the transcriptional changes induced by miR-190
      expression in cancer cells and show similar patterns of miR-190 mediated
      transcriptional reprogramming in both glioblastoma and osteosarcoma cells. The
      data suggests that miR-190 mediated effects rely on an extensive network of
      molecular changes in tumor cells and that miR-190 affects several transcriptional
      factors, tumor suppressor genes and interferon response pathways. The molecular
      mechanisms governing tumor dormancy described in this work may provide promising
      targets for early prevention of cancer and may lead to novel treatments to
      convert the malignant tumor phenotype into an asymptomatic dormant state. 

PMID- 23863202
TI  - Comments on "Efficacy and safety of desmopressin orally disintegrating tablet in
      patients with central diabetes insipidus: results of a multicenter open-label
      dose-titration study"--efficacy and safety of orally disintegrating desmopressin
      tablets in patients with central diabetes insipidus.

PMID- 23863203
TI  - In vivo proton range verification: a review.
AB  - Protons are an interesting modality for radiotherapy because of their well
      defined range and favourable depth dose characteristics. On the other hand, these
      same characteristics lead to added uncertainties in their delivery. This is
      particularly the case at the distal end of proton dose distributions, where the
      dose gradient can be extremely steep. In practice however, this gradient is
      rarely used to spare critical normal tissues due to such worries about its exact
      position in the patient. Reasons for this uncertainty are inaccuracies and non
      uniqueness of the calibration from CT Hounsfield units to proton stopping powers,
      imaging artefacts (e.g. due to metal implants) and anatomical changes of the
      patient during treatment. In order to improve the precision of proton therapy
      therefore, it would be extremely desirable to verify proton range in vivo, either
      prior to, during, or after therapy. In this review, we describe and compare state
      of-the art in vivo proton range verification methods currently being proposed,
      developed or clinically implemented. 

PMID- 23863201
TI  - A new role for an old player: steroid receptor RNA Activator (SRA) represses
      hormone inducible genes.
AB  - In breast cancer cells the Steroid Receptor !RNA Activator (SRA) acts as scaffold
      of a complex containing HP1gamma, LSD1, HDAC1/2 and CoREST, which contributes to
      repression of key hormone-inducible genes that must be kept silent in the absence
      of hormone. 

PMID- 23863204
TI  - Miniinvasive surgical management of cholelithiasis for elderly and senile
      patients: a retrospective study.
AB  - The aim of the present study is to analyze outcomes after laparoscopic
      cholecystectomy (LC) and minilaparotomy cholecystectomy (MC) for gallstone
      disease and determine the algorithm of treatment for elderly and senile patients
      according to the age, severity of disease and comorbid conditions. This is a
      multicenter retrospective review of 906 elderly and senile patients who underwent
      LC or MC between January 1, 2002 and December 31, 2008. The patients were
      categorized into LC (444) and MC (462) groups. When preoperative examination data
      were not reliable, we performed abdominal wall lifting with the retractors to
      visualise abdominal cavity with laparoscope during minilaparotomy. There were
      statistically significant differences in mean operating time (82 and 60 minutes
      in LC and MC, respectively) (r<0.001), mean duration of usage of non-narcotic
      analgesics postoperatively in elderly patients (1.5 and 1.1 days in LC and MC,
      respectively) (r<0.001), intraoperative complications (11 LC and 2 MC cases)
      (p=0.02), postoperative complications in senile patients (36 LC and 22 MC cases)
      (p=0.039) and in mean hospital stay for elderly patients (1.7 and 1.3 days in LC
      and MC, respectively) (p=0.025). MC is an attractive alternative of LC,
      especially for elderly and senile patients, with their high incidence of acute
      cholecystitis. MC is effective, safe and optimal operative procedure. Especially,
      it is important for countries with lower economic capacity. 

PMID- 23863205
TI  - Clinical parallels in treatment of reversible pulpitis.
AB  - Current study is aiming at comparative characterization of clinical aspects of
      preparations, containing calcium hydroxide, in the treatment of pulp hyperemia
      (primary pulpitis). With this aim two products, made on the base of calcium
      hydroxide, were selected: Ultra-Blend (Ultradent) and Life (Kerr). The results
      obtained after application of these materials were compared with the results
      obtained in patients affected with the similar pathology, where Ca(OH)2
      containing liners were not used in treatment process. 54 teeth were selected for
      the study, among them - 38 molars and 16 premolars. Patients were divided into
      three groups: I group (21 teeth) included the patients who underwent pulp
      hyperemia treatment with Life, II group - patients treated with Ultra-Blend (19
      teeth) and III group - patients without any pulp protections respectively (13
      teeth). It was decided to perform treatment assessment and making appropriate
      conclusions according to two factors: degree of adhesion of restorations to teeth
      surfaces and teeth post-restorative sensitivity. Comparison of the obtained data
      of study and control groups revealed weakening of adhesion between filling and
      tooth tissues practically in all 3groups, however, with different rate and
      intensity: in I group on radioography micro cracks were revealed in 10 cases
      (47.6%), II group -7 (36.5%) cases and treating group - 4 (30.7%) cases,
      respectively. The obtained results of the current study revealed non-homogenous
      picture: in I group where Kerr liner was applied - hypersensitivity was revealed
      in 12 (57.1%) cases, II group - 6 (31.5%) and III group - 7 (53.8%) cases. It is
      concluded that the primary reason for teeth prolonged and enhanced sensitivity is
      a micro-percolation factor into the perimeter. But if we admit the application of
      medical liners in the treatment of pulp hyperemia, doctor's choice should be made
      on those, providing maximum prevention of further complications. At this stage of
      the study such features were better revealed by Ultra-Blend. However, the final
      clinical outcomes - pulp hyperemia disappearance, no complains, production of
      tertiary dentin and so on - might be expected within a year after the end of the
      treatment. Currently, it will be interesting to study the pulp chamber condition,
      evaluation of electrophysiological parameters of the tooth and restoration
      quality. The mentioned issues will be studied in the future studies. 

PMID- 23863206
TI  - [Root and canal morphology of maxillary first premolar in Georgian population].
AB  - Almost each stage of endodontic treatment is connected with structural
      peculiarities of teeth. One of the biggest challenges facing clinicians is
      profound knowledge of root canal systems which is different in various races and
      ethnic groups. This study is devoted to the investigation of anatomo
      morphological peculiarities of maxillary first premolar in Georgian population.
      The purpose of our work is to study anatomo-morphological and anthropological
      data of permanent teeth among Georgian population, establish average statistical
      indices of tooth length, peculiarities of "canals system", make correlation of
      the obtained results with international statistical indices. The data obtained as
      a result of clinical and laboratory studies must be assumed as a basis for making
      new tables of anatomo-morphological statistical indices of teeth roots and canals
      for Georgian population. Statistical index by itself is not a universal criterion
      because anthropometric data of roots and canals according to nationality and
      geographical zones are subjected to variations. The investigation done by us is a
      visible example of this. 

PMID- 23863207
TI  - [Comparison of the therapeutic effect of the Warfarin and Rivaroksaban among the
      patients with not-valuate fibrillation of atrium].
AB  - In this article the results of comparative assessment of the efficiency of the
      Rivaroksaban and Varfarine for prevention of stroke and systemic embolic
      complications in middle and high- stroke risk patients with nonvalvular artial
      fibrillation are presented. Detailed analysis of some risk factors is conducted
      according to scales: CHADS2, CHA2DS2-VASc and HAS-BLED. The frequency of
      development of endpoints is defined (stroke, TIA, system embolism, cardiac
      infarction or death due to cardiovascular reasons, or combination of outcomes)
      according to initial risk and anticoagulant treatment. Connection between
      "retention" of INR and the risk of the thromboembolic and hemorrhagic
      complications in patients treated with Varfarine are analyzed. 

PMID- 23863208
TI  - [Meglumine acridonacetate in combined antiviral treatment of HBeAg-positive
      chronic hepatitis B].
AB  - 647 patients with HBeAg positive chronic hepatitis B who have not previously
      received antiviral therapy were participated in randomized, post-marketing,
      double-blinded, placebo-controlled clinical trial. Interferon inducer cycloferon
      was presented as study drug. 323 patients with chronic hepatitis B (HBV) with
      "wild" HBeAg(+) strain of HBV were treated with cycloferon and Lamivudin for 48
      weeks. Control group included 324 patients with similar pathology, treated with
      Lamivudin and placebo for 48 weeks. The study has shown the benefit of
      cycloferon+lamivudin treatment in comparison with lamivudin monotherapy.
      Improving of liver histology in 48 weeks of the therapy was observed in 71% of
      patients in Study group in comparison with 57% in control group (p<0.01).
      Combined therapy has resulted in decrease of relapse by 24 week of the follow-up
      period (13% vs. 86%, p<0.001). The higher efficacy of cycloferon+lamivudin in
      patients with HBeAg positive chronic hepatitis B has proven the role of own
      antiviral effect of interferon inducer cycloferon, interferon effect of
      cycloferon in the elimination of virus-infected hepatocytes, as well as the
      presence of an immunomodulatory effect of the preparation, aimed at the
      elimination of HBeAg and HBsAg with the following seroconversion. 48-week course
      of combined antiviral therapy of HBeAg-positive patients with chronic hepatitis B
      is recommended as first-line therapy for patients with HBeAg-positive chronic
      hepatitis B, who have not previously received nucleoside analogues, as well as
      alternative therapy of Lamivudin-refractory patients. 

PMID- 23863209
TI  - Prognostic value of EEG in different etiological types of coma.
AB  - Study aimed at evaluation of prognostic value of standard EEG in different
      etiology of coma and the influence of etiological factor on the EEG patterns and
      coma outcome. Totally 175 coma patients were investigated. Patients were
      evaluated by Glasgow Coma Scale (GCS), clinically and by 16 channel
      electroencephalography. Auditory evoked potentials studied by EEG -regime for
      evoked potentials in patients with vegetative state (VS). Patients divided in 8
      groups according to coma etiology. All patients were studied for photoreaction,
      brainstem reflexes, localization of sound and pain, length of coma state and
      outcome. Brain injury visualized by conventional CT. Outcome defined as death,
      VS, recovery with disability and without disability. Disability was rated by
      Disability Rating Scale (DRS). Recovered patients assessed by Mini Mental State
      Examination (MMSE) scale. Statistics performed by SPSS-11.0. From 175 coma
      patients 55 patients died, 23 patients found in VS, 97 patients recovered with
      and without disability. In all etiological groups of coma the background EEG
      patterns were established. Correspondence analysis of all investigated factors
      revealed that sound localization had the significant association with EEG delta
      and theta rhythms and with recovery from coma state (Chi-sqr. =31.10493; p=
      0.000001). Among 23 VS patients 9 patients had the signs of MCS and showed the
      long latency waves (p300) after binaural stimulation. The high amplitude theta
      frequencies in frontal and temporal lobes significantly correlated with
      prolongation of latency of cognitive evoked potentials (r=+0.47; p<0.01).
      Etiological factor had the significant effect on EEG patterns' association with
      coma outcome only in hemorrhagic and traumatic coma (chi-sqr.=12.95; p<0.005; chi
      sqr.=7.92; p<0.03 respectively). Significant correlations established between the
      delta and theta EEG patterns and coma outcome. Low amplitude decreased power
      delta and theta frequencies correlated with SND in survived coma patients
      (r=+0.21; p<0.001; r=+0.27; p<0.001 respectively). Standard EEG is the useful
      tool for elucidation of coma patients with a high probability to recover as well
      as those patients, who are at high risk of SND in case of recovery from coma
      state.

PMID- 23863210
TI  - [Effect of probiotics on the dynamics of gastrointestinal symptoms of food
      allergy to cow's milk protein in infants].
AB  - The problem of food allergy to cow's milk protein in children is highly
      important. The aim of this study was to estimate the effect of Bifidobacterium
      lactis BB-12 (1x109 CFU) and Streptococcus thermophilus TH-4 (1x108 CFU)
      administration on gastrointestinal symptoms of cow's milk allergy in infants. We
      conducted an open randomized prospective clinical study. 60 infants aged of 3-12
      months with the diagnosis of atopic dermatitis and allergy to cow's milk protein
      were enrolled. Children were divided into 2 groups, one of which received
      probiotics during 4 weeks. Results were estimated after 4 and 8 weeks of study.
      We found significant impact on reducing the frequency of constipation in infants
      who received the probiotics in complex treatment. After 4 weeks of treatment
      constipation was absent in 85.71% infants who received probiotics as compared to
      48.15% in the control group (r=0.02), after 8 weeks the same numbers were 92.86%
      vs. 62.96% accordingly (p=0.04). Significant differences between the groups were
      also determined by the incidences of infantile colic through 4 and 8 weeks and on
      diarrhea through 8 weeks of studies. It is possible to draw a conclusion that
      administration of probiotics in addition to elimination diet and base treatment
      to infants with atopic dermatitis and cow's milk allergy improves clinical
      symptoms of the disease and decreases gastrointestinal clinical manifestations of
      cow's milk allergy. 

PMID- 23863211
TI  - [Gene of glucocorticoid receptor: structure, polymorphism and clinical
      associations].
AB  - The article provides modern information about the structure of glucocorticoid
      receptor gene and its isoforms, the most common variants of missens and allelic
      polymorphisms. The polymorphisms N363S, BclI, ER22/23EK and TthIIII were
      characterized. The relationship of these polymorphisms with physique and
      metabolic changes, cardiovascular system diseases as well as with sensitivity to
      glucocorticoids (GCS) was analyzed. It has been established that N363S and BclI
      polymorphisms are associated with hypersensitivity to corticosteroids and can be
      the predictors of obesity, metabolic syndrome, and polymorphisms ER22/23EK and
      TthIIII are associated with resistance to GC and favorable metabolic profile. 

PMID- 23863212
TI  - Development and implementation of the internal audit mechanisms to be used in the
      health care facilities.
AB  - Issues concerning the quality of care service improvement have become of national
      importance in the health-care system for both developed and developing countries.
      Internal audit is effective and efficient method to improve the quality of care
      in various health care facilities. Data from 452 outpatient cards of the case
      patients with arterial hypertension were analyzed, the level of awareness and
      patient compliance were defined. The stages of internal audit mechanisms
      implementation in the health care facilities were developed. As a result of
      medical records audit and awareness monitoring of patients with arterial
      hypertension ways to improve quality of medical care were defined. 

PMID- 23863213
TI  - The use of drugs Impaza and Nebido in the treatment of erectile dysfunction in
      patients with type 2 diabetes mellitus of reproductive age.
AB  - The main objective of the study was to investigate the efficacy of using a mono
      and combined therapy drugs Impaza and Nebido for secondary prevention and
      treatment of ED. It was examined 79 diabetic patients with ED. The age of
      patients within 18-60 years, duration of diabetes - from 6 months to 29 years, ED
      - from 6 months to 12 years. To identify the ED was used International index of
      erectile function (IIEF). The patients were divided into 3 groups: I - patients
      with organic ED, II - with psychogenic ED and III group - with mixed ED. Drags
      Impaza and Nebido used in all three groups, as mono or as complex therapy. It was
      using routine (anamnesis, clinico- biochemical data) and special
      (pharmacodopplerography) methods of study. The study did not include patients
      with increased level of prostate-specific antigen (PSA), polycythemia,
      obstruction of the urinary tract with the prostate size increasing and prostate
      cancer. Statistical data was studed by using Pearson's chi2-test. The results
      showed the following. Indicators of glycohemoglobin above normal reduces the
      effectiveness of the treatment of erectile dysfunction in patients with diabetes
      mellitus.The combined use of drugs Impaza and Nebido in patients with ED had a
      positive resultes in 41,4-91,7% of the cases. These drugs are effective in
      diabetic patients with mild and moderate form of erectile dysfunction. 

PMID- 23863214
TI  - [Organization and improvement of emergency medical care for industrial city
      population in republic of Kazakhstan].
AB  - The aim of the research was to develop recommendations for organization and
      improvement of emergency medical care in Shymkent (Chimkent) - a rapidly
      developing financial and industrial center in Southern Kazakhstan. It was found
      that the average annual daily load of iresuscitative teams and pediatric
      intensive care increased, which is associated with an increased frequency of
      severe cases, complications of disease of adults and children requiring intensive
      care therapy. Another objective measure that reflects the level of organization
      of Acute care of population is the specialization of rig team and timeliness
      arrival of the call. The highest level of the specialization of rig was observed
      in cardiac and critical care teams. The highest level of the indicator of average
      residence time teams on the call was observed in pediatric intensive care. 

PMID- 23863215
TI  - Gate-induced transition between metal-type and thermally activated transport in
      self-catalyzed MBE-grown InAs nanowires.
AB  - Electronic transport properties of InAs nanowires are studied systematically. The
      nanowires are grown by molecular beam epitaxy on a SiOx-covered GaAs wafer,
      without using foreign catalyst particles. Room-temperature measurements revealed
      relatively high resistivity and low carrier concentration values, which correlate
      with the low background doping obtained by our growth method. Transport
      parameters, such as resistivity, mobility, and carrier concentration, show a
      relatively large spread that is attributed to variations in surface conditions.
      For some nanowires the conductivity has a metal-type dependence on temperature,
      i.e. decreasing with decreasing temperature, while other nanowires show the
      opposite temperature behavior, i.e. temperature-activated characteristics. An
      applied gate voltage in a field-effect transistor configuration can switch
      between the two types of behavior. The effect is explained by the presence of
      barriers formed by potential fluctuations. 

PMID- 23863216
TI  - Short communication: cerebrospinal fluid lactate and pyruvate concentrations and
      ratio in healthy adult dogs.

PMID- 23863218
TI  - How often do our liver core biopsies reach current definitions of adequacy?
AB  - Needle core biopsy is a key tool in diagnosis and assessment of many medical
      liver diseases, but there is evidence that the combination of small size of the
      specimen obtained and the patchy nature of many of these diseases can result in
      misdiagnosis or incorrect staging. The Royal College of Pathologists has
      therefore published guidelines for assessment of adequacy. To assess whether
      these guidelines were being observed, we reviewed cases reported in our
      department over a 15-year period. Results showed that only 19.8% of cores would
      be considered adequate, 56.4% were suboptimal and 23.8% were inadequate. We
      discuss the issues around recommendations on the minimum size of liver biopsies,
      potential factors limiting biopsy size and whether further refinement of the
      guidelines for adequacy is required. 

PMID- 23863217
TI  - Investigations of the low-frequency spectral density of cytochrome c upon
      equilibrium unfolding.
AB  - The equilibrium unfolding process of ferric horse heart cytochrome c (cyt c),
      induced by guanidinium hydrochloride (GdHCl), was studied using UV-vis absorption
      spectroscopy, resonance Raman spectroscopy, and vibrational coherence
      spectroscopy (VCS). The unfolding process was successfully fit using a three
      state model which included the fully folded (N) and unfolded (U) states, along
      with an intermediate (I) assigned to a Lys bound heme. The VCS spectra revealed
      for the first time several low-frequency heme modes that are sensitive to cyt c
      unfolding: gamma(a) (~50 cm(-1)), gamma(b) (~80 cm(-1)), gamma(c) (~100 cm(-1)),
      and nu(s)(His-Fe-His) at 205 cm(-1). These out-of-plane modes have potential
      functional relevance and are activated by protein-induced heme distortions. The
      free energies for the N-I and the I-U transitions at pH 7.0 and 20  degrees C
      were found to be 4.6 kcal/M and 11.6 kcal/M, respectively. Imidazole was also
      introduced to replace the methionine ligand so the unfolding can be modeled as a
      two-state system. The intensity of the mode gamma(b)~80 cm(-1) remains nearly
      constant during the unfolding process, while the amplitudes of the other low
      frequency modes track with spectral changes observed at higher frequency. This
      confirms that the heme deformation changes are coupled to the protein tertiary
      structural changes that take place upon unfolding. These studies also reveal that
      damping of the coherent oscillations depends sensitively on the coupling between
      heme and the surrounding water solvent.

PMID- 23863219
TI  - A core needle biopsy provides more malignancy-specific results than fine-needle
      aspiration biopsy in thyroid nodules suspicious for malignancy.
AB  - BACKGROUND AND AIMS: The most commonly used diagnostic method for the
      preoperative diagnosis of thyroid nodules is ultrasound-guided fine-needle
      aspiration biopsy (FNA), which often yields non-diagnostic or non-definitive
      results and seldom produces definite malignant diagnoses. To improve upon the
      malignancy-specific sensitivity, we tested core needle biopsies (CNBs) of thyroid
      lesions taken from surgical specimens. MATERIAL AND METHODS: 52 consecutive
      patients with malignant or malignant-suspicious thyroid nodules were referred to
      Tampere University Hospital between May 2010 and December 2011. Preoperative FNAs
      were categorised as follicular neoplasm (48%), suspicion for malignancy (46%) or
      malignancy (6%). Intraoperative FNA and CNB samples were acquired from surgical
      specimens removed during surgery. The results of the needle biopsies were
      compared with the final pathological diagnosis. RESULTS: CNBs had a high
      definitive sensitivity for malignancy (61%, CI 41% to 78%) whereas the definitive
      sensitivity for malignancy of FNAs was significantly lower (22%, CI 10% to 42%).
      CNB was not beneficial in the diagnosis of follicular thyroid lesions. When all
      suspected follicular tumours were excluded, the definitive sensitivity of CNB
      rose to 70% (CI 48% to 86%). CONCLUSIONS: CNB may be beneficial for the diagnosis
      of papillary thyroid carcinoma and other non-follicular thyroid lesions. CNB may
      be considered as an additional diagnostic procedure in cases with FNA suspicious
      for malignancy.

PMID- 23863221
TI  - Moving some articles to electronic (online) only publication.

PMID- 23863220
TI  - Sex-specific assessment of reduced coronary sinus flow in non-hypertensive
      patients with coronary artery disease at rest.
AB  - BACKGROUND: Access to data on the coronary flow in the coronary sinus (CS) can
      aid in the diagnosis of coronary artery disease (CAD). We tested the hypothesis
      that assessing the CS flow by transthoracic Doppler echocardiography (TTE) at
      rest can detect coronary artery stenosis in non-hypertensive patients. METHODS:
      The antegrade phase of coronary flow in the CS was analyzed and compared in 140
      male and 135 female non-hypertensive subjects who had all undergone coronary
      angiography. RESULTS: There were statistically significant differences noted
      between males and females for the CS flow both in normal subjects and patients
      with CAD. Compared with normal subjects, patients with CAD had significantly
      lower blood flow in the CS both in males (196.6+/-174.31 vs. 367.65+/-168.04
      ml/min, P<0.01) and females (183.04+/-65.46 vs. 244.13+/-135.43 ml/min P<0.01).
      For males, the diagnostic sensitivity, specificity, and accuracy of the cutoff
      value of the CS flow (206 ml/min) for predicting a significant coronary artery
      stenosis (>70%) were 91.67%, 81.25%, and 85.71%, respectively. For females, those
      of the cutoff value of the CS flow (195 ml/min) were 85.71%, 75%, and 80%,
      respectively. CONCLUSION: TTE can effectively detect coronary hemodynamically
      significant stenosis in non-hypertensive male and female patients at different
      cutoff values.

PMID- 23863222
TI  - Value and limitations of transpulmonary pressure calculations during intra
      abdominal hypertension.
AB  - OBJECTIVE: To clarify the effect of progressively increasing intra-abdominal
      pressure on esophageal pressure, transpulmonary pressure, and functional residual
      capacity. DESIGN: Controlled application of increased intra-abdominal pressure at
      two positive end-expiratory pressure levels (1 and 10 cm H2O) in an anesthetized
      porcine model of controlled ventilation. SETTING: Large animal laboratory of a
      university-affiliated hospital. SUBJECTS: Eleven deeply anesthetized swine
      (weight 46.2 +/- 6.2 kg). INTERVENTIONS: Air-regulated intra-abdominal
      hypertension (0-25 mm Hg). MEASUREMENTS: Esophageal pressure, tidal compliance,
      bladder pressure, and end-expiratory lung aeration by gas dilution. MAIN RESULTS:
      Functional residual capacity was significantly reduced by increasing intra
      abdominal pressure at both positive end-expiratory pressure levels (p <= 0.0001)
      without corresponding changes of end-expiratory esophageal pressure. Above intra
      abdominal pressure 5 mm Hg, plateau airway pressure increased linearly by ~ 50%
      of the applied intra-abdominal pressure value, associated with commensurate
      changes of esophageal pressure. With tidal volume held constant, negligible
      changes occurred in transpulmonary pressure due to intra-abdominal pressure.
      Driving pressures calculated from airway pressures alone (plateau airway pressure
      -positive end-expiratory pressure) did not equate to those computed from
      transpulmonary pressure (tidal changes in transpulmonary pressure). Increasing
      positive end-expiratory pressure shifted the predominantly negative end
      expiratory transpulmonary pressure at positive end-expiratory pressure 1 cm H2O
      (mean -3.5 +/- 0.4 cm H2O) into the positive range at positive end-expiratory
      pressure 10 cm H2O (mean 0.58 +/- 1.2 cm H2O). CONCLUSIONS: Despite its
      insensitivity to changes in functional residual capacity, measuring
      transpulmonary pressure may be helpful in explaining how different levels of
      positive end-expiratory pressure influence recruitment and collapse during tidal
      ventilation in the presence of increased intra-abdominal pressure and in
      calculating true transpulmonary driving pressure (tidal changes of transpulmonary
      pressure). Traditional interpretations of respiratory mechanics based on
      unmodified airway pressure were misleading regarding lung behavior in this
      setting.

PMID- 23863223
TI  - Influence of ICU case-volume on the management and hospital outcomes of acute
      exacerbations of chronic obstructive pulmonary disease*.
AB  - OBJECTIVES: To study the relationship between case-volume and the use of
      noninvasive ventilation during acute exacerbations of chronic obstructive
      pulmonary disease in ICUs. DESIGN: A 13-year multicenter retrospective cohort
      study of prospectively collected data. SETTING: Medical ICUs. PATIENTS: From 1998
      to 2010, patients with acute exacerbations of chronic obstructive pulmonary
      disease were identified through a regional database. INTERVENTIONS: The
      characteristics of hospitalization (including the type of mechanical ventilation)
      and demographic data of the patients were analyzed. ICUs were categorized into
      tertiles of the running mean annual volume of admissions. A logistic model
      performed a conditional multivariate analysis of prognostic factors after
      matching on a propensity score of being admitted to a high-volume unit and on the
      year of admission. MEASUREMENTS AND MAIN RESULTS: Fourteen thousand four hundred
      forty acute exacerbations of chronic obstructive pulmonary disease were
      identified. The Simplified Acute Physiology Score II and ICU mortality increased
      during the study period (36 to 41 and 12% to 14%, respectively). The proportion
      of patients receiving any mechanical ventilation support also increased during
      the study period (from 64% to 86%), with a marked increase in the use of
      noninvasive ventilation (from 18% to 49%) and a decrease in the use of invasive
      ventilation (from 34% to 19%). Participating units were distributed into low
      volume (< 25 patients per year), medium-volume (26-47 patients per year), and
      high-volume (> 47 patients per year) tertiles. There was a significant
      association between case-volume and 1) the proportion of patients receiving
      noninvasive ventilation (highest vs lowest case-volume tertiles: odds ratio, 1.43
      [95% CI, 1.23-1.66]) and 2) lower mortality. CONCLUSIONS: Between 1998 and 2010,
      severity and mortality of acute exacerbations of chronic obstructive pulmonary
      disease admitted to College des Utilisateurs de Donnees en Reanimation ICUs
      increased. There was an increasing use of noninvasive ventilation and a
      decreasing use of invasive ventilation. Use of noninvasive ventilation was
      related to case-volume, suggesting that increasing experience favors the use of
      noninvasive ventilation and was associated with a strong trend toward decreased
      mortality.

PMID- 23863224
TI  - Effect of a multifaceted performance feedback strategy on length of stay compared
      with benchmark reports alone: a cluster randomized trial in intensive care*.
AB  - OBJECTIVE: To assess the impact of applying a multifaceted activating performance
      feedback strategy on intensive care patient outcomes compared with passively
      receiving benchmark reports. DESIGN: The Information Feedback on Quality
      Indicators study was a cluster randomized trial, running from February 2009 to
      May 2011. SETTING: Thirty Dutch closed-format ICUs that participated in the
      national registry. Study duration per ICU was sixteen months. PATIENTS: We
      analyzed data on 25,552 admissions. Admissions after coronary artery bypass graft
      surgery were excluded. INTERVENTION: The intervention aimed to activate ICUs to
      undertake quality improvement initiatives by formalizing local responsibility for
      acting on performance feedback, and supporting them with increasing the impact of
      their improvement efforts. Therefore, intervention ICUs established a local,
      multidisciplinary quality improvement team. During one year, this team received
      two educational outreach visits, monthly reports to monitor performance over
      time, and extended, quarterly benchmark reports. Control ICUs only received four
      standard quarterly benchmark reports. MEASUREMENTS AND RESULTS: The extent to
      which the intervention was implemented in daily practice varied considerably
      among intervention ICUs: the average monthly time investment per quality
      improvement team member was 4.1 hours (SD, 2.3; range, 0.6-8.1); the average
      number of monthly meetings per quality improvement team was 5.7 (SD, 4.5; range,
      0-12). ICU length of stay did not significantly reduce after 1 year in
      intervention units compared with controls (hazard ratio, 1.02 [95% CI, 0.92
      1.12]). Furthermore, the strategy had no statistically significant impact on any
      of the secondary measures (duration of mechanical ventilation, proportion of out
      of-range glucose measurements, and all-cause hospital mortality). CONCLUSIONS: In
      the context of ICUs participating in a national registry, applying a multifaceted
      activating performance feedback strategy did not lead to better patient outcomes
      than only receiving periodical registry reports.

PMID- 23863225
TI  - Safety of intrahospital transport in ventilated critically ill patients: a
      multicenter cohort study*.
AB  - OBJECTIVES: To describe intrahospital transport complications in critically ill
      patients receiving invasive mechanical ventilation. DESIGN: Prospective
      multicenter cohort study. SETTING: Twelve French ICUs belonging to the OUTCOMEREA
      study group. PATIENTS: Patients older than or equal to 18 years old admitted in
      the ICU and requiring invasive mechanical ventilation between April 2000 and
      November 2010 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Six thousand two hundred forty-two patients on invasive mechanical ventilation
      were identified in the OUTCOMEREA database. The statistical analysis included a
      description of demographic and clinical characteristics of the cohort,
      identification of risk factors for intrahospital transport and construction of an
      intrahospital transport propensity score, and an exposed/unexposed study to
      compare complication of intrahospital transport (excluding transport to the
      operating room) after adjustment on the propensity score, length of stay, and
      confounding factors on the day before intrahospital transport. Three thousand and
      six intrahospital transports occurred in 1,782 patients (28.6%) (1-17
      intrahospital transports/patient). Transported patients had higher admission
      Simplified Acute Physiology Score II values (median [interquartile range], 51 [39
      65] vs 46 [33-62], p < 10) and longer ICU stay lengths (12 [6-23] vs 5 [3-11] d,
      p < 10). Post-intrahospital transport complications were recorded in 621 patients
      (37.4%). We matched 1,659 intrahospital transport patients to 3,344
      nonintrahospital transport patients according to the intrahospital transport
      propensity score and previous ICU stay length. After adjustment, intrahospital
      transport patients were at higher risk for various complications (odds ratio =
      1.9; 95% CI, 1.7-2.2; p < 10), including pneumothorax, atelectasis, ventilator
      associated pneumonia, hypoglycemia, hyperglycemia, and hypernatremia.
      Intrahospital transport was associated with a longer ICU length of stay but had
      no significant impact on mortality. CONCLUSIONS: Intrahospital transport
      increases the risk of complications in ventilated critically ill patients.
      Continuous quality improvement programs should include specific procedures to
      minimize intrahospital transport-related risks.

PMID- 23863226
TI  - Bacteremia in patients with acute pancreatitis as revealed by 16S ribosomal RNA
      gene-based techniques*.
AB  - OBJECTIVES: To define the characteristic of bacteremia in patients with acute
      pancreatitis and determine its possible association with the disease severity.
      DESIGN: A prospective controlled study. SETTING: ICU of Jinling Hospital, China.
      PATIENTS: A total of 48 patients with mild or severe acute pancreatitis were
      enrolled in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Samples of peripheral blood were collected from the patients at 4 or 5 and 9 or
      10 days after acute pancreatitis was definitely diagnosed. Resulting DNA from the
      blood was analyzed using denaturing gradient gel electrophoresis, and separated
      fragments were sequenced for identification of bacterial species. Bacterial DNA
      was detected in peripheral blood from 68.8% of patients with acute pancreatitis,
      and more than half (60.4%) of the patients encountered polymicrobial flora.
      Translocated bacteria in patients with acute pancreatitis were primarily
      constituted of opportunistic pathogens derived from the gut, including
      Escherichia coli, Shigella flexneri, Enterobacteriaceae bacterium, Acinetobacter
      lwoffii, Bacillus coagulans, and Enterococcus faecium. The species of circulating
      bacteria shifted remarkably among the patients with different severity. The
      presence of the bacteremia correlated positively with the Acute Physiology and
      Chronic Health Evaluation-II scores of patients with acute pancreatitis (r =
      0.7918, p < 0.0001). CONCLUSIONS: This study provides a detailed description on
      the prevalence of bacteremia and characteristic of bacterial species in patients
      with acute pancreatitis. We demonstrate an association between the bacteremia and
      the disease severity, which enables us to better understand a potential role of
      bacterial translocation in the pathogenesis of septic complication in acute
      pancreatitis.

PMID- 23863227
TI  - Pleural pressure and optimal positive end-expiratory pressure based on esophageal
      pressure versus chest wall elastance: incompatible results*.
AB  - OBJECTIVES: 1) To compare two published methods for estimating pleural pressure,
      one based on directly measured esophageal pressure and the other based on chest
      wall elastance. 2) To evaluate the agreement between two published positive end
      expiratory pressure optimization strategies based on these methods, one targeting
      an end-expiratory esophageal pressure-based transpulmonary pressure of 0 cm H2O
      and the other targeting an end-inspiratory elastance-based transpulmonary
      pressure of 26 cm H2O. DESIGN: Retrospective study using clinical data. SETTING:
      Medical and surgical ICUs. PATIENTS: Sixty-four patients mechanically ventilated
      for acute respiratory failure with esophageal balloons placed for clinical
      management. METHODS: Esophageal pressure and chest wall elastance-based methods
      for estimating pleural pressure and setting positive end-expiratory pressure were
      retrospectively applied to each of the 64 patients. In patients who were
      ventilated at two positive end-expiratory pressure levels, chest wall and
      respiratory system elastances were calculated at each positive end-expiratory
      pressure level. MEASUREMENTS AND MAIN RESULTS: The pleural pressure estimates
      using both methods were discordant and differed by as much as 10 cm H2O for a
      given patient. The two positive end-expiratory pressure optimization strategies
      recommended positive end-expiratory pressure changes in opposite directions in
      33% of patients. The ideal positive end-expiratory pressure levels recommended by
      the two methods for each patient were discordant and uncorrelated (R = 0.05).
      Chest wall and respiratory system elastances grew with increases in positive end
      expiratory pressure in patients with positive end-expiratory esophageal pressure
      based transpulmonary pressures (p < 0.05). CONCLUSIONS: Esophageal pressure and
      chest wall elastance-based methods for estimating pleural pressure do not yield
      similar results. The strategies of targeting an end-expiratory esophageal
      pressure-based transpulmonary pressure of 0 cm H2O and targeting an end
      inspiratory elastance-based transpulmonary pressure of 26 cm H2O cannot be
      considered interchangeable. Finally, chest wall and respiratory system elastances
      may vary unpredictably with changes in positive end-expiratory pressure.

PMID- 23863228
TI  - Atypical sleep in ventilated patients: empirical electroencephalography findings
      and the path toward revised ICU sleep scoring criteria.
AB  - OBJECTIVES: Standard sleep scoring criteria may be unreliable when applied to
      critically ill patients. We sought to quantify typical and atypical
      polysomnographic findings in critically ill patients and to begin development and
      reliability testing of methodology to characterize the atypical polysomnographic
      tracings that confound standard sleep scoring criteria. DESIGN: Prospective
      convenience sample. SETTING: Two academic, tertiary care medical centers.
      PATIENTS: Thirty-seven critically ill, mechanically ventilated, medical ICU
      patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mechanically
      ventilated subjects were monitored by continuous polysomnography. After noting
      frequent atypical polysomnographic findings (i.e., lack of stage N2 markers, the
      presence of polymorphic delta, burst suppression, or isoelectric
      electroencephalography), attempts to use standard sleep scoring criteria alone
      were abandoned. Atypical polysomnographic findings were characterized and used to
      develop a modified scoring system. Polysomnographic data were scored manually via
      this revised scoring scheme. Of 37 medical ICU patients enrolled, 36 experienced
      atypical sleep, which accounted for 85% of all recorded data, with 5.1% normal
      sleep and 9.4% wake. Coupling observed patient arousal levels with
      polysomnographic characteristics revealed that standard polysomnographic staging
      criteria did not reliably determine the presence or absence of sleep. Rapid eye
      movement occurred in only five patients (14%). The revised scoring system
      incorporating frequently seen atypical characteristics yielded very high
      interrater reliability (weighted kappa = 0.80; bootstrapped 95% CI, [0.48,
      0.89]). CONCLUSIONS: Analysis of polysomnographic data revealed profound
      deficiencies in standard scoring criteria due to a predominance of atypical
      polysomnographic findings in ventilated patients. The revised scoring scheme
      proved reliable in sleep staging and may serve as a building block in future
      work.

PMID- 23863229
TI  - Clostridium difficile infection: a multicenter study of epidemiology and outcomes
      in mechanically ventilated patients.
AB  - OBJECTIVES: Clostridium difficile is a leading cause of hospital-associated
      infection in the United States. The purpose of this study is to assess the
      prevalence of C. difficile infection among mechanically ventilated patients
      within the ICUs of three academic hospitals and secondarily describe the
      influence of C. difficile infection on the outcomes of these patients. DESIGN: A
      retrospective cohort study. SETTING: ICUs at three teaching hospitals: Barnes
      Jewish Hospital, Mayo Clinic, and Creighton University Medical Center over a 2
      year period. PATIENTS: All hospitalized patients requiring mechanical ventilation
      for greater than 48 hours within an ICU were eligible for inclusion.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 5,852 consecutive
      patients admitted to the ICU were included. Three hundred eighty-six (6.6%)
      patients with development of C. difficile infection while in the hospital (5.39
      cases/1,000 patient days). Septic shock complicating C. difficile infection
      occurred in 34.7% of patients. Compared with patients without C. difficile
      infection (n = 5,466), patients with C. difficile infection had a similar
      hospital mortality rate (25.1% vs 26.3%, p = 0.638). Patients with C. difficile
      infection were significantly more likely to be discharged to a skilled nursing or
      rehabilitation facility (42.4% vs 31.9%, p < 0.001), and the median hospital (23
      d vs 15 d, p < 0.001) and ICU length of stay (12 d vs 8 d, p < 0.001) were found
      to be significantly longer in patients with C. difficile infection. CONCLUSIONS:
      Clostridium difficile infection is a relatively common nosocomial infection in
      mechanically ventilated patients and is associated with prolonged length of
      hospital and ICU stay, and increased need for skilled nursing care or
      rehabilitation following hospital discharge.

PMID- 23863230
TI  - Early goal-directed sedation versus standard sedation in mechanically ventilated
      critically ill patients: a pilot study*.
AB  - OBJECTIVE: To assess the feasibility and safety of delivering early goal-directed
      sedation compared with standard sedation. DESIGN: Pilot prospective, multicenter,
      randomized, controlled trial. SETTING: Six ICUs. PATIENTS: Critically ill adults
      mechanically ventilated for greater than 24 hours. INTERVENTIONS: Patients
      randomized to early goal-directed sedation received a dexmedetomidine-based
      algorithm targeted to light sedation (Richmond Agitation Sedation Score of -2 to
      1). Patients randomized to standard sedation received propofol and/or midazolam
      based sedation as clinically appropriate. MEASUREMENTS AND MAIN RESULTS: The main
      feasibility outcomes were time to randomization and proportion of Richmond
      Agitation Sedation Score assessments in the first 48 hours in the light and deep
      sedation range. Safety outcomes were delirium-free days, vasopressor and physical
      restraints use, and device removal. Randomization occurred within a median
      (interquartile range) of 1.1 hours (0.46-1.9) after intubation or ICU admission
      for out of ICU intubation. Patients in the early goal-directed sedation (n = 21)
      mean (SD) Acute Physiology and Chronic Health Evaluation II score was 20.2 (6.2)
      versus 18.6 (8.8; p = 0.53) in the standard sedation (n = 16). A significantly
      higher proportion of patients was lightly sedated on days 1, 2, and 3 (12/19
      [63.2%], 19/21 [90.5%], and 18/20 [90%] vs 2/14 [14.3%], 8/15 [53.3%], and 9/15
      [60%]; p = 0.005, 0.011, 0.036) and more Richmond Agitation Sedation Scale
      assessments between (-2 and 1), in the first 48 hours (203/307 [66%] versus
      (74/197 [38%]; p = 0.01) in the early goal-directed sedation versus standard
      sedation, respectively. Early goal-directed sedation patients received midazolam
      on 6 of 173 (3.5%) versus 4 of 114 (3.5%) standard sedation patient-days when
      dexmedetomidine was given. Propofol was given to 16 of 21 (76%) of early goal
      directed sedation versus 16 of 16 (100%) of standard sedation patients (p =
      0.04). Early goal-directed sedation patients had 101 of 175 (58%) versus 54 of
      114 (47%; p = 0.27) delirium-free days and required significantly less physical
      restraints 1 (5%) versus 5 (31%; p = 0.03) than standard sedation patients. There
      were no differences in vasopressor use and self-extubation. CONCLUSIONS: Delivery
      of early goal-directed sedation was feasible, appeared safe, achieved early light
      sedation, minimized benzodiazepines and propofol, and decreased the need for
      physical restraints. The findings of this pilot study justify further
      investigation of early goal-directed sedation.

PMID- 23863231
TI  - Evaluating pain, sedation, and delirium in the neurologically critically ill
      feasibility and reliability of standardized tools: a multi-institutional study.
AB  - OBJECTIVES: To assess the feasibility and reliability of systematic evaluations
      of analgesia, sedation level, and delirium features in the neurologically
      critically ill and to determine whether delirium features are linked to clinical
      outcomes in this population. DESIGN: Multicentered prospective observational
      study. SETTING: Neurological, Neurosurgical, Neurosciences or Surgical Trauma
      ICUs from three hospitals (two in Canada and one in the United States). PATIENTS:
      A convenience sample of adult NICU or neurologic, neurosurgical, neurosciences,
      or surgical trauma ICU patients admitted for greater than 12 hours from November
      2011 to April 2012. INTERVENTIONS: Systematic assessments were simultaneously and
      independently performed by a neurologist, intensivists, or trauma surgeon, and a
      nurse in three multispecialty ICUs. Pain was evaluated with the numeric rating
      scale or behavioral pain scale. Sedation was assessed using the Richmond
      Agitation-Sedation Scale. Patients with Richmond Agitation-Sedation Scale greater
      than or equal to -4 were screened for features of delirium with the Intensive
      Care Delirium Screening Checklist. Intraclass correlation coefficient was used to
      evaluate inter-rater reliability between the nurse and the physician for pain and
      sedation scales, and the kappa coefficient was calculated for concordance of the
      Intensive Care Delirium Screening Checklist items. MEASUREMENTS AND MAIN RESULTS:
      151 patients had 439 assessments. Pain and sedation were always assessable with
      excellent inter-rater reliability (numeric rating scale intraclass correlation
      coefficient, 0.92; behavior pain scale intraclass correlation coefficient, 0.83;
      and Richmond Agitation-Sedation Scale intraclass correlation coefficient, 0.92).
      Patients were sufficiently alert for delirium screening 3/4 of the time;
      Intensive Care Delirium Screening Checklist items had good concordance (kappa
      coefficients between 0.58 and 0.91 for the eight Intensive Care Delirium
      Screening Checklist items). Nonevaluable items were most often orientation,
      hallucinations, and speech or mood content. Furthermore, each additional
      Intensive Care Delirium Screening Checklist item present in proportion to the
      total evaluable Intensive Care Delirium Screening Checklist score was associated
      with a 10% increase in ICU length of stay. CONCLUSIONS: Pain and sedation can be
      systematically assessed in the neurologically critically ill; the majority can
      also be screened for delirium features with excellent inter-rater reliability.
      Increased proportion of Intensive Care Delirium Screening Checklist items is
      associated with worse outcomes.

PMID- 23863233
TI  - Healthcare resource utilization and costs after critical illness: current
      knowledge and a plan for moving forward*.

PMID- 23863234
TI  - The risks of pregnancy in the 21st century*.

PMID- 23863232
TI  - In silico modeling: methods and applications to trauma and sepsis.
AB  - OBJECTIVES: To familiarize clinicians with advances in computational disease
      modeling applied to trauma and sepsis. DATA SOURCES: PubMed search and review of
      relevant medical literature. SUMMARY: Definitions, key methods, and applications
      of computational modeling to trauma and sepsis are reviewed. CONCLUSIONS:
      Computational modeling of inflammation and organ dysfunction at the cellular,
      organ, whole-organism, and population levels has suggested a positive feedback
      cycle of inflammation -> damage -> inflammation that manifests via organ-specific
      inflammatory switching networks. This structure may manifest as multicompartment
      "tipping points" that drive multiple organ dysfunction. This process may be
      amenable to rational inflammation reprogramming.

PMID- 23863235
TI  - Status epilepticus in sepsis: do the mysteries of the magical black box elude us
      yet again?*.

PMID- 23863236
TI  - Trending the fever curve: what does it tell us?*.

PMID- 23863237
TI  - Transpulmonary pressure: the unknown nature of lung inflation*.

PMID- 23863238
TI  - "Bigger is better?" what drives outcomes in management of acute exacerbations of
      chronic obstructive pulmonary disease?*.

PMID- 23863239
TI  - Quality assessing the quality assessment*.

PMID- 23863240
TI  - Does plasma transfusion therapy have a role in clinical medicine?*.

PMID- 23863241
TI  - "Airborne assault": a new dimension in Acinetobacter baumannii transmission*.

PMID- 23863242
TI  - Reducing the risks of intrahospital transport among critically ill patients*.

PMID- 23863243
TI  - Walking acute respiratory distress syndrome: a target for treatment and
      prevention?*.

PMID- 23863244
TI  - Demonstrating infection in severe acute pancreatitis: a role for polymerase chain
      reaction and gene sequencing?*.

PMID- 23863245
TI  - Selecting optimum positive end-expiratory pressure: seeing the forest instead of
      the trees*.

PMID- 23863246
TI  - Optimizing evidence-based ICU sedation*.

PMID- 23863247
TI  - Out with the old or better use of the old? A quest in sedation*.

PMID- 23863248
TI  - Acute respiratory distress syndrome: rather a (vague) concept than a (clear)
      definition*.

PMID- 23863249
TI  - Effective communication on ICU rounds: can we master competency for this
      procedure?*.

PMID- 23863250
TI  - Changing the focus in acute respiratory distress syndrome: treating is mandatory,
      but preventing is imperative*.

PMID- 23863251
TI  - Inotropic effect of lipid emulsion: a new perspective*.

PMID- 23863252
TI  - The future has arrived*.

PMID- 23863253
TI  - Can chest sonography predict and facilitate successful ventilator weaning?*.

PMID- 23863254
TI  - Specific antibody in IV immunoglobulin for postsplenectomy sepsis.
AB  - OBJECTIVE: Overwhelming postsplenectomy infection progresses rapidly and shows
      unacceptably high mortality even when treated with optimal antibiotics. Recent
      reports have described beneficial effects of intravenous immunoglobulin in
      sepsis. However, the underlying mechanisms, especially the roles of the pathogen
      specific antibody fraction in intravenous immunoglobulin, remain unclear. We
      investigated the effects of intravenous immunoglobulin on overwhelming
      postsplenectomy infection and the role of pathogen-specific antibody. DESIGN:
      Prospective, controlled, and randomized animal study. SETTING: University
      laboratory. SUBJECTS: Male C57BL/6JJcl mice. INTERVENTIONS: Mice underwent
      splenectomy or a sham operation at 8 weeks old. At 4 weeks after the operation,
      mice were injected intravenously with 106 colony-forming units pneumococcus.
      Intraperitoneal injection of 300 mg/kg IV immunoglobulins was conducted
      simultaneously with infection. Specific antibody-depleted IV immunoglobulin
      prepared using immunoprecipitation was also injected into the animals.
      MEASUREMENTS AND MAIN RESULTS: IV immunoglobulin markedly improved splenectomized
      mice survival. Removal of pneumococcus-specific antibody canceled it completely.
      Fluorescence microscopy results indicated significantly increased phagocytosis of
      antibody-bound bacteria in the livers of splenectomized mice treated with intact
      IV immunoglobulins. Immunomodulation, including suppression of marginal zone B
      cell activation, was induced by IV immunoglobulin. CONCLUSIONS: IV immunoglobulin
      showed a significantly protective effect on overwhelming postsplenectomy
      infection via enhancement of specific antibody-mediated phagocytosis in the
      liver. Specific antibody, more than immunological modulation, is crucial for
      effects of IV immunoglobulin on overwhelming postsplenectomy infection.

PMID- 23863255
TI  - Usefulness of combined bedside lung ultrasound and echocardiography to assess
      weaning failure from mechanical ventilation: a suggestive case*.
AB  - OBJECTIVE: Recognition of the cardiac origin of weaning failure is a crucial
      issue for successful discontinuation of mechanical ventilation. Bedside lung
      ultrasound and echocardiography have shown a potential in predicting weaning
      failure. Objective of this report was to describe the case of a patient
      repeatedly failing to wean from mechanical ventilation, where the combined use of
      lung ultrasound and echocardiography during a spontaneous breathing trial
      uncovered an unexpected cause of the failure. DESIGN: Case report. SETTING:
      General ICU of a university teaching hospital. PATIENTS: Single case, abdominal
      surgery postoperative patient, not predicted to experience a difficult weaning.
      INTERVENTIONS: Cardiovascular therapy adjustments consistent with lung ultrasound
      and echocardiography findings acquired during spontaneous breathing trials.
      MEASUREMENTS AND MAIN RESULTS: All patient's standard hemodynamic and respiratory
      parameters, datasets from comprehensive lung ultrasound and echocardiographic
      examinations, and pertinent data from biochemistry exams, were collected during
      two spontaneous breathing trials. Data from beginning and end of each of the two
      ultrasound monitored weaning trials, and from the end of the successful weaning
      trial following therapy and the previously failed one, were analyzed and
      qualitatively compared. Lung ultrasound performed at the end of the failed
      spontaneous breathing trial showed a pattern consistent with increased
      extravascular lung water (diffuse, bilateral, symmetrical, homogeneous
      sonographic interstitial syndrome). Concurrent echocardiography diagnosed left
      ventricular diastolic failure. Ultrasound findings at the end of the successful
      weaning trial showed normalization of the lung pattern and improvement of the
      echocardiographic one. The patient eventually returned to spontaneous respiration
      and was discharged from the ICU. CONCLUSIONS: The use of bedside lung ultrasound
      and echocardiography disclosed left ventricular diastolic dysfunction as
      unexpected cardiogenic cause of weaning failure and lead to subsequent correct
      patient management.

PMID- 23863256
TI  - Cell-free hemoglobin: a new player in sepsis pathophysiology.

PMID- 23863257
TI  - The authors reply.

PMID- 23863258
TI  - Antiplatelet therapy in bleeding trauma patients: tales of the unexpected.

PMID- 23863259
TI  - Sedative and analgesic drugs.

PMID- 23863260
TI  - The authors reply.

PMID- 23863261
TI  - Antibiotic susceptibility of Helicobacter pylori in central Germany and its
      relationship with the number of eradication therapies.
AB  - OBJECTIVES: Helicobacter pylori eradication rates show a constant decline over
      the last few years. The main reason for H. pylori treatment failure is the
      increasing antibiotic resistance.We assessed antibiotic susceptibility of H.
      pylori in a region of mid-Germany and analyzed the relationship of antibiotic
      resistance with the number of eradication therapies over a period of 7 years
      (2005-2012). METHODS: H. pylori strains were isolated from 436 patients who
      underwent gastroscopy for different clinical indications. Susceptibility to
      amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and
      rifabutin was determined using the E-test. RESULTS: Primary, secondary, and
      tertiary resistances against clarithromycin were 7.5, 63.2, and 75.4%,
      respectively. Primary, secondary, and tertiary resistances to levofloxacin were
      11.7, 17.6, and 36.4% and to metronidazole were 32.7, 63.2, and 80.1%,
      respectively. The resistance rates against tetracycline and rifabutin were
      comparatively low (<5%), even in patients with previous exposure to these
      antibiotics. Resistance to rifabutin increased to 6.2% in patients who received
      more than two previous eradication therapies. Amoxicillin resistance was not
      detectable in all patients. CONCLUSION: In our region, we observed a stable, but
      constantly increasing, resistance rate to antibiotics commonly used for the
      treatment of H. pylori infection. Knowledge of the local antibiotic resistance
      rates is essential for developing successful treatment strategies for H. pylori
      eradication.

PMID- 23863262
TI  - Features of massive hepatocellular carcinomas.
AB  - BACKGROUND: Massive hepatocellular carcinomas (HCCs) are uncommon and poorly
      characterized. AIM: To characterize a large cohort of HCC patients with massive
      tumors, with documented baseline characteristics and survival data. METHODS:
      Records were examined of a cohort of 344 biopsy-proven and randomly presenting
      unresectable HCC patients with tumors of at least 10 cm diameter (massive), which
      were analyzed for their clinical characteristics and survival. RESULTS: Massive
      HCC patients were significantly different from others, in having less severe
      cirrhosis and higher blood platelet counts, alpha-fetoprotein (AFP), alkaline
      phosphatase (ALKP), and gamma-glutamyl transpeptidase (GGTP) levels. Platelets,
      ALKP, and GGTP correlated with tumor size. Within massive HCCs, ALKP levels
      related to tumor number, whereas platelet counts related to tumor size. AFP and
      GGTP related to neither. All four parameters related to survival. A multivariate
      Cox proportional hazard model showed that ALKP and AFP were significant for
      overall survival. Survival of massive tumors was not significantly worse than for
      other larger tumors. CONCLUSION: Massive HCCs were characterized by high blood
      platelets, AFP, ALKP, and GGTP levels. AFP levels were important for survival,
      but did not directly relate to tumor size or number, suggesting that AFP
      represents some other property of massive HCC biology. Patients with massive HCC
      should thus be considered for active therapeutic intervention, just as for other
      sizes of HCC.

PMID- 23863264
TI  - Chemical design of nanocrystal solids.
AB  - This account highlights our recent and present activities dedicated to chemical
      synthesis and applications of inorganic nanostructures. In particular, we discuss
      the potential of metal amides as precursors in the synthesis of metallic and
      semiconductor nanocrystals. We show the importance of surface chemical
      functionalization for the emergence of collective electronic properties in
      nanocrystal solids. We also demonstrate a new kind of long-range ordered,
      crystalline matter comprising colloidal nanocrystals and atomically defined
      inorganic clusters. Finally, we point the reader's attention to the high
      potential benefits of size- and shape-tunability of nanocrystals for achieving
      higher performance of rechargeable Li-ion battery electrodes. 

PMID- 23863265
TI  - Atomic mutagenesis of the ribosome: towards a molecular understanding of
      translation.
AB  - The multifaceted repertoire of non-protein-coding RNAs (ncRNAs) in organisms of
      all three domains of life emphasizes their fundamental role in biology. Research
      in my lab focuses on revealing the regulatory and catalytic function of small and
      large ncRNAs in different model organisms. In particular we are interested in
      understanding ncRNA/protein complexes such as the vault complex or the ribosome.
      The ribosome, the central enzyme of protein biosynthesis, is a multifunctional
      ribonucleoprotein particle composed of two unequal subunits that translates the
      genome's message into all proteins needed for life. The crucial role the
      translation machinery plays in gene expression is also mirrored by the fact that
      the ribosome represents the main target for antibiotics. Decades of genetic,
      biochemical and recent crystallographic studies revealed the ribosome as an RNA
      enzyme with roots in the 'RNA world'. Despite these experimental insights, the
      catalytic and regulatory mechanisms of the ribosomal RNA are still not fully
      understood at the molecular level. To unravel the detailed contributions of rRNA
      nucleotides for protein synthesis we have developed and applied an 'atomic
      mutagenesis' approach. This tool allows the role of specific 23S rRNA functional
      groups and even individual atoms to be studied during various stages of the
      ribosomal elongation cycle with thus far unequalled precision. This experimental
      approach bridges the disciplines of biochemistry and organic chemistry and has
      recently revealed specific functional 23S rRNA groups involved in peptide bond
      synthesis, peptidyl-tRNA hydrolysis, GTPase activation, and tRNA translocation. 

PMID- 23863266
TI  - Hierarchical zeolites overcome all obstacles: next stop industrial
      implementation.
AB  - This review emphasizes key recent accomplishments towards the industrial
      exploitation of hierarchically structured zeolites in catalytic processes. A
      major milestone comprises the demonstration that affordable post-synthetic
      modifications enable the transformation of any conventional zeolite into
      hierarchical analogues with tunable porosity and functionality. Through specific
      examples, belonging to the transformation of fossil fuel and renewable
      feedstocks, we quantitatively illustrate the spectacular benefits attained upon
      application of hierarchical zeolite catalysts due to improved accessibility or
      modification of the type and distribution of active sites. A crucial step for
      these exciting lab-designed materials to be implemented in industrial processes
      is to shape them into technical forms. Accordingly, we studied the synthesis,
      characterization, and catalytic evaluation of millimeter-sized hierarchical
      zeolite bodies, enriching the fundamental understanding on scale-up and
      representing an additional solid step towards the commercial application of these
      materials. 

PMID- 23863267
TI  - Thiohistidine biosynthesis.
AB  - Ergothioneine and ovothiol A are sulfur-containing histidine derivatives produced
      by microorganisms including Mycobacterium tuberculosis, Trypanosoma cruzi or
      Erwinia amylovora and may also play important roles in human physiology. Based on
      our recent identification of thiohistidine biosynthetic enzymes from
      Mycobacterium smegmatis and Erwinia tasmaniensis we investigate several aspects
      of sulfur-based redox biochemistry. For example, we are characterizing the
      catalytic mechanism of two thiohistidine biosynthetic enzymes which afford O2
      dependent sulfur insertion into the C(5)-H and C(2)-H bonds of the imidazolyl
      side chain of histidine. 

PMID- 23863268
TI  - Photoinduced electron and proton transfer with metal complexes and organic
      molecules.
AB  - This article provides an overview of some of the research performed in the
      author's group over the past few years. This includes work on organic mixed
      valence species with photoisomerizable components, as well as studies of proton
      coupled electron transfer between photoexcited metal complexes and organic
      reaction partners. This research relies on a combination of synthetic work with
      optical spectroscopic and electrochemical studies, and the results are relevant
      in the greater context of light-to-chemical energy conversion. 

PMID- 23863269
TI  - Nucleic acid-programmed assemblies: translating instruction into function in
      chemical biology.
AB  - The predictability of nucleic acid hybridization offers an attractive platform to
      program the assembly of tagged ligands or reactants. Hybridization can be used to
      display multiple ligands in order to gain affinity and/or selectivity through the
      cooperative interaction of each ligand. Additionally, hybridization of tagged
      reagents increases their effective concentration and accelerates reactions. In
      both cases, an oligonucleotide directs an assembly to yield a functional output
      in the form of enhanced binding, inhibition, or reaction; for example, a reaction
      can be used to unmask a fluorophore or a bioactive molecule. This review provides
      an account of our research in this area as well as future directions. 

PMID- 23863274
TI  - The evaluation of mindfulness-based stress reduction for veterans with mental
      health conditions.
AB  - PURPOSE: To assess the feasibility of mindfulness-based stress reduction (MBSR)
      for veterans with mental health conditions and to evaluate its efficacy on
      psychological well-being and stress reduction. DESIGN: Single-group, pretest
      posttest design. METHOD: 30 veterans within a mental health clinic of a VA
      (Veterans Administration) medical center were enrolled in an 8-week standard MBSR
      program. Perceived stress, sleep, mindfulness, and depression were measured via
      self-reports at baseline and study end. Feasibility was measured by compliance
      and satisfaction with the course. FINDINGS: Scores on the Perceived Stress Scale
      (p =.002) and Beck Depression Inventory-II (p = .005) were significantly reduced
      (p = .002). The global measure for sleep from the Pittsburgh Sleep Quality Index
      improved significantly (p = .035). Satisfaction and compliance were high.
      CONCLUSION: MBSR is a feasible intervention that has potential efficacy for
      veterans with mental health conditions. Future controlled trials are needed in
      this area.

PMID- 23863275
TI  - Spirituality measurement in African American cancer survivors: a critical
      literature review.
AB  - PURPOSE: Spirituality is a mechanism that supports coping with chronic illnesses
      such as cancer, and has been frequently used in the African American (AA)
      population. Measures of spirituality are needed, which are culturally sensitive,
      appropriate, and psychometrically sound. DESIGN: A critical literature review was
      performed to identify instruments measuring spirituality as a response to
      illness. METHOD: Whittemore and Knafl's method was used to search pertinent
      databases for instrumentation assessing spirituality and its applicability in AA
      cancer survivors. FINDINGS: In all, 13 research articles detailing nine
      instruments were obtained and included for analysis. Of the nine instruments,
      only two (Perspectives of Support From God Scale and Connections to God Scale)
      were psychometrically tested in populations of AAs who had completed primary
      treatment for their cancer. Cultural validity was tested in only the Perspectives
      of Support From God Scale, showing a deficit in the assessment of cultural
      appropriateness of these instruments to the population. CONCLUSIONS: Further
      research is needed to confirm validity of these measures. Cognitive pretesting
      and assessment of cross-cultural validity can be used to ensure proper
      understanding of terminology and avoid potential biases. Repeated testing of the
      instrument in the desired population is necessary to confirm that constructs and
      items are understood and cognitively processed as intended.

PMID- 23863276
TI  - Shunichi Usami, as remembered by Shu Chien.

PMID- 23863277
TI  - Giant intracranial aneurysm embolization with a yield stress fluid material:
      insights from CFD analysis.
AB  - The endovascular treatment of intracranial aneurysms remains a challenge,
      especially when the aneurysm is large in size and has irregular, non-spherical
      geometry. In this paper, we use computational fluid dynamics to simulate blood
      flow in a vertebro-basilar junction giant aneurysm for the following three cases:
      (1) an empty aneurysm, (2) an aneurysm filled with platinum coils, and (3) an
      aneurysm filled with a yield stress fluid material. In the computational model,
      blood and the coil-filled region are treated as a non-Newtonian fluid and an
      isotropic porous medium, respectively. The results show that yield stress fluids
      can be used for aneurysm embolization provided the yield stress value is 20 Pa or
      higher. Specifically, flow recirculation in the aneurysm and the size of the
      inflow jet impingement zone on the aneurysm wall are substantially reduced by
      yield stress fluid treatment. Overall, this study opens up the possibility of
      using yield stress fluids for effective embolization of large-volume intracranial
      aneurysms. 

PMID- 23863278
TI  - How preservation time changes the linear viscoelastic properties of porcine
      liver.
AB  - The preservation time of a liver graft is one of the crucial factors for the
      success of a liver transplantation. Grafts are kept in a preservation solution to
      delay cell destruction and cellular edema and to maximize organ function after
      transplantation. However, longer preservation times are not always avoidable. In
      this paper we focus on the mechanical changes of porcine liver with increasing
      preservation time, in order to establish an indicator for the quality of a liver
      graft dependent on preservation time. A time interval of 26 h was covered and the
      rheological properties of liver tissue studied using a stress-controlled
      rheometer. For samples of 1 h preservation time 0.8% strain was found as the
      limit of linear viscoelasticity. With increasing preservation time a decrease in
      the complex shear modulus as an indicator for stiffness was observed for the
      frequency range from 0.1 to 10 Hz. A simple fractional derivative representation
      of the Kelvin Voigt model was applied to gain further information about the
      changes of the mechanical properties of liver with increasing preservation time.
      Within the small shear rate interval of 0.0001-0.01 s-1 the liver showed
      Newtonian-like flow behavior.

PMID- 23863279
TI  - Rate dependent biomechanical properties of corneal stroma in unconfined
      compression.
AB  - The corneal stroma is a highly ordered extracellular matrix and mainly
      responsible for the mechanical strength of the cornea. The rate dependent
      mechanical and rheological properties of the cornea are not completely understood
      and there is large variation in the reported estimates. In this work, the rate
      dependent mechanical behavior of the corneal stroma was investigated using
      experimental studies and theoretical models. Unconfined compression stress
      relaxation experiments at different displacement rates and compressive strains
      were conducted. The unconfined compression material parameters, i.e. corneal out
      of-plane modulus, in-plane modulus and permeability coefficient were determined
      from curve-fitting the experimental data with a transversely isotropic biphasic
      model. It was found that the maximum force reached during the step loading
      increased with both increasing magnitude and rate of the compressive strain. It
      was also observed that at all loading rates the in-plane Young's modulus
      increased with increasing strain, while the permeability coefficient decayed with
      increasing compressive strain. At a constant compressive strain, both the in
      plane Young's modulus and the permeability coefficient increased with increasing
      the loading rate. Regardless of loading rates and compressive strains, a range of
      corneal out-of-plane modulus of 0.6 kPa to 13.8 kPa, in-plane modulus of 0.5 MPa
      to 4.8 MPa, and permeability coefficient of 1*10-14 m4/N.s to 7*10-14 m4/N.s was
      found.

PMID- 23863280
TI  - Segregation by size difference in binary suspensions of fluid droplets in channel
      flow.
AB  - In channel flow of multicomponent suspensions, segregation behavior of suspended
      components perpendicular to the flow direction is often observed, which is
      considered to be caused by the differential properties of the lateral migration
      depending on their shape, size, flexibility, and other characteristics. In the
      present study, we investigate the effect of size differences between suspended
      components on the segregation behavior, by a two-dimensional numerical simulation
      for binary dispersed suspensions of fluid droplets of two different sizes
      subjected to a plane Poiseuille channel flow. The small and large droplets are
      assumed to have equal surface tensions and equal viscosity ratios of internal to
      external fluids. The time evolutions of the lateral positions of large and small
      droplets relative to the channel centerline were computed by changing the area
      fraction of the small droplets in a mixture with a constant total area fraction.
      The large droplets are found to migrate closer to the channel centerline and the
      small droplets are found to migrate closer to the channel wall compared to the
      corresponding lateral positions in mono-dispersed suspensions at the same area
      fractions, although the mean lateral positions of the large and small droplets in
      mono-dispersed suspension are comparable. This segregation behavior as well as
      the margination of small droplets are enhanced when the size difference between
      large and small droplets is increased and the area fraction of large droplets is
      increased. These results may arise from higher tendencies for the large droplets
      to approach the channel centerline compared to the small droplets, which
      consequently expel small droplets from the central region toward the channel
      walls. 

PMID- 23863281
TI  - Shear stress-induced improvement of red blood cell deformability.
AB  - Classically, it is known that red blood cell (RBC) deformability is determined by
      the geometric and material properties of these cells. Experimental evidence
      accumulated during the last decade has introduced the concept of active
      regulation of RBC deformability. This regulation is mainly related to altered
      associations between membrane skeletal proteins and integral proteins, with the
      latter serving to anchor the skeleton to the lipid matrix. It has been
      hypothesized that shear stress induces alterations of RBC deformability: the
      current study investigated the dynamics of the transient improvement in
      deformability induced by shear stress at physiologically-relevant levels. RBC
      were exposed to various levels of shear stress (SS) in a Couette type shearing
      system that is part of an ektacytometer, thus permitting the changes in RBC
      deformability during the application of SS to be monitored. Initial studies
      showed that there is an increase in deformability of the RBC subjected to SS in
      the range of 5-20 Pa, with kinetics characterized by time constants of a few
      seconds. Such improvement in deformability, expressed by an elongation index
      (EI), was faster with higher levels of SS and hence yielded shorter time
      constants: absolute values of EI increased by 3-8% of the starting level. Upon
      the removal of the shear stress, this response by RBC was reversible with a
      slower time course compared to the increase in EI during application of SS.
      Increased calcium concentration in the RBC suspending medium prevented the
      improvement of deformability. It is suggested that the improvement of RBC
      deformability by shear forces may have significant effects on blood flow
      dynamics, at least in tissues supplied by blood vessels with impaired vasomotor
      reserve, and may therefore serve as a compensating mechanism for the maintenance
      of adequate microcirculatory perfusion. 

PMID- 23863282
TI  - The viscous characterization of hydroxyethyl starch (HES) plasma volume expanders
      in a non-Newtonian blood analog.
AB  - Although information pertaining to the viscous characterization of HES 130/0.4
      Voluven(r) and HES 260/0.45 Pentaspan(r) is available, quantification is limited
      to 100% concentrations. We focus here on the quantification of their viscous
      behavior along with HES 130/0.4 Volulyte(r) in a shear thinning non-Newtonian
      blood analog of aqueous xanthan gum and glycerol. Dynamic viscosities of multiple
      batches of HES fluids were measured through capillary viscometry. The viscous
      behavior of 100%, 25% and 12.5% concentrations were then measured through a
      closed flow loop across physiologically relevant flow rates. Measured viscosities
      were 2.57 millipascal second (mPa.s) 6.52 mPa.s and 2.48 mPa.s for HES 130/0.4
      Voluven(r), HES 260/0.45 and HES 130/0.4 Volulyte(r), respectively. Pipe flow
      analysis found that all HES fluids displayed Newtonian behavior at 100%
      concentrations. 25% concentrations of both HES 130/0.4 fluids decreased analog
      viscosity 23%-29% at a flow rate of 1.0 ml/s and 16%-21% at a flow rate of 22.5
      ml/s. At a flow rate of 22.5 ml/s, 25% and 12.5% concentrations of HES 260/0.45
      resulted in analog viscosity changes of 3.9%-4.5%. Capillary viscosity reductions
      of approximately 7% and 14.5% in HES 130/0.4 Voluven(r) and HES 260/0.45 suggest
      changes in molecular composition to batches previously measured. Maintenance of
      analog viscosity suggests that HES 260/0.45 would be suitable as a high viscosity
      plasma expander in extreme hemodilution through preservation of microcirculatory
      function and wall shear stress (WSS). 

PMID- 23863283
TI  - Squeeze film lubrication for non-Newtonian fluids with application to manual
      medicine.
AB  - In this paper, we computed fluid pressure and force on fascia sheets during
      manual therapy treatments using Squeeze Film Lubrication theory for non-Newtonian
      fluids. For this purpose, we developed a model valid for three dimensional fluid
      flow of a non-Newtonian liquid. Previous models considered only one-dimensional
      flows in two dimensions. We applied this model to compare the one-dimensional
      flow of HA, considered as a lubricating fluid, around or within the fascia during
      sliding, vibration, and back-and-forth sliding manipulation treatment techniques.
      The fluid pressure of HA increases dramatically as fascia is deformed during
      manual therapies. The fluid force increases more during vertical vibratory
      manipulation treatment than in constant sliding, and back and forth motion. The
      variation of fluid pressure/force causes HA to flow near the edges of the fascial
      area under manipulation in sliding and back and forth motion which may result in
      greater lubrication. The fluid pressure generated in manual therapy techniques
      may improve sliding and permit muscles to work more efficiently. 

PMID- 23863284
TI  - Numerical simulation of biofilm growth in flow channels using a cellular
      automaton approach coupled with a macro flow computation.
AB  - Biofilm is a slime-like complex aggregate of microorganisms and their products,
      extracellular polymer substances, that grows on a solid surface. The growth
      phenomenon of biofilm is relevant to the corrosion and clogging of water pipes,
      the chemical processes in a bioreactor, and bioremediation. In these phenomena,
      the behavior of the biofilm under flow has an important role. Therefore,
      controlling the biofilm behavior in each process is important. To provide a
      computational tool for analyzing biofilm growth, the present study proposes a
      computational model for the simulation of biofilm growth in flows. This model
      accounts for the growth, decay, detachment and adhesion of biofilms. The proposed
      model couples the computation of the surrounding fluid flow, using the finite
      volume method, with the simulation of biofilm growth, using the cellular
      automaton approach, a relatively low-computational-cost method. Furthermore, a
      stochastic approach for considering the adhesion process is proposed. Numerical
      simulations for the biofilm growth on a planar wall and that in an L-shaped
      rectangular channel were carried out. A variety of biofilm structures were
      observed depending on the strength of the flow. Moreover, the importance of the
      detachment and adhesion processes was confirmed. 

PMID- 23863285
TI  - Human vaccines & immunotherapeutics: news.
AB  - Recent advances in the development of immunotherapeutic mAbs for cancer New
      vaccine reduces malaria infection by 72% Bavarian Nordic's cancer immunotherapy
      shows promise in colorectal cancer Chinese HFMD vaccine shows high efficacy in
      Phase 3 Two-dose regimen of Merck's Gardasil looks effective Accelerating
      influenza vaccine development using synthetic biology A key role for gut microbes
      in vaccination Understanding of and attitudes towards vaccines: a study in
      teenagers.

PMID- 23863286
TI  - Letter from the editor.

PMID- 23863287
TI  - Novel cutinase from Pseudomonas cepacia NRRL B 2320: purification,
      characterization and identification of cutinase encoding genes.
AB  - An extracellular cutinase from Pseudomonas cepacia NRRL B 2320 was purified to
      apparent homogeneity. Upon biochemical characterization, the purified cutinase
      was found to be tolerant to organic solvents and surfactants under assay
      conditions. The molecular mass of cutinase was found to be 26.25 kDa by MALDI-TOF
      MS analysis. The enzyme was able to show activity towards synthetic esters of
      chain length C4-C16. The activity of cutinase was enhanced by mono cations and
      various effectors, whereas it was moderately inhibited by various divalent
      cations and serine blocking reagent, phenyl methyl sulphonyl fluoride (PMSF). The
      optimal pH and temperature for highest activity were found to be 7.9 and 36.5
      degrees C, respectively. An overall 1.42-fold increase in activity was observed
      after optimization of both assay and process conditions. The exposure of
      hydrophobic amino acid to an aqueous environment and change in secondary
      structure of cutinase was observed from thermodynamic parameters (DeltaH(*),
      DeltaS(*)), fluorescence and circular dichorism spectra during the deactivation
      process. Two cutinase encoding genes were identified in P. cepacia, cloned and
      expressed in E. coli BL21 (DE3).

PMID- 23863288
TI  - Providencia thailandensis sp. nov., isolated from seafood processing wastewater.
AB  - The bacterial strain C1112(T) was isolated from seafood processing wastewater
      collected from a treatment pond of the seafood factory in Songkhla Province,
      Thailand. Phylogenetic analysis based on concatenated sequences from the 16S rRNA
      gene and five housekeeping genes, fusA, lepA, leuS, gyrB and ileS respectively
      showed that the strain C1112(T) belonged to the genus Providencia, and share
      91.75% similarity with P. stuartii DSM 4539(T). DNA-DNA hybridization between the
      strain C1112(T) and P. stuartii KCTC 2568(T) was 48.1% relatedness. Moreover,
      some results from biochemical properties indicated that the strain C1112(T) was
      distinguished from the phylogenetically closest relatives. The major fatty acids
      of the strain C1112(T) were C16:0, iso-C15:0, C14:0 and C17:0 cyclo and the DNA
      G+C content was 41 mol%. Based on the genotypic and phenotypic considerations, it
      should be classified as a novel species of the genus Providencia for which the
      name Providencia thailandensis sp. nov. is proposed. The type strain is C1112(T)
      (= KCTC 23281(T) =NBRC 106720(T)).

PMID- 23863289
TI  - Candida phyllophila sp. nov. and Candida vitiphila sp. nov., two novel yeast
      species from grape phylloplane in Thailand.
AB  - Three strains (K59(T), K60 and K70 (T)) representing two novel yeast species were
      isolated from the external surface of leaves of different wine grape (Vitis
      vinifera) plants, which were collected from the Kanchanaburi Research Station
      (N14 degrees 07'15.1" E099 degrees 19'05.6"), Wang Dong Sub-district, Mueang
      District, Kanchanaburi Province, Thailand, by an enrichment technique. The
      sequences of the D1/D2 domain of the large subunit (LSU) rRNA gene of two strains
      (K59(T) and K60) were identical and differed from that of strain K70(T). In terms
      of pairwise sequence similarity of the D1/D2 domain, the closest species to the
      three strains was Candida asparagi but with 2.3% nucleotide substitutions for
      strains K59(T) and K60, and 2.1% nucleotide substitutions for strain K70(T). On
      the basis of morphological, biochemical, physiological and chemotaxonomic
      characteristics and the sequence analysis of the D1/D2 domain of the large
      subunit (LSU) rRNA gene, the three strains were assigned to be two novel Candida
      species. Two strains (K59(T) and K60) were assigned as Candida phyllophila sp.
      nov. (type strain K59(T)=BCC 42662(T)=NBRC 107776(T)=CBS 12671(T)). Candida
      vitiphila sp. nov. is proposed for strain K70(T) (=BCC 42663(T)=NBRC
      107777(T)=CBS 12672(T)).

PMID- 23863290
TI  - Rhizobacter gummiphilus sp. nov., a rubber-degrading bacterium isolated from the
      soil of a botanical garden in Japan.
AB  - A rubber-degrading bacterium, the strain NS21, that was isolated from a soil
      sample in a botanical garden in Japan (Imai et al., 2011) was examined by
      phenotypic, phylogenetic and chemotaxonomic approaches to determine its taxonomic
      position. The strain NS21 was motile, possessing a single polar flagellum and a
      facultatively anaerobic straight rod. Analysis of the 16S rRNA and gyrB gene
      sequences of NS21 revealed a close relationship to the genus Rhizobacter. The
      predominant quinone type was Q-8. The G+C content of the NS21 genomic DNA was
      70.8 mol%. The major fatty acids were C16:0, C17:0 cyclo, C18:1omega7c and
      C16:1omega7c and/or iso-C15:0 2-OH. C12:0 2-OH was present. The DNA-DNA
      hybridization experiments indicated that the DNA relatedness values of the strain
      NS21 to R. dauci H6(T) and R. fulvus Gsoil 322(T) were lower than 24%. The
      phenotypic characteristics showed obvious dissimilarities when compared to
      closely related species. On the basis of these taxonomic properties, a novel
      species is proposed as Rhizobacter gummiphilus sp. nov., with the strain NS21(T)
      (NBRC 109400(T), BCC 58006(T)) as the type strain. The emended description of the
      genus Rhizobacter was also presented.

PMID- 23863291
TI  - A role of the transcriptional regulator LldR (NCgl2814) in glutamate metabolism
      under biotin-limited conditions in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum is a Gram-positive, rod-shaped, aerobic bacterium used
      for the fermentative production of L-glutamate. LldR (NCgl2814) is known as a
      repressor for ldhA and lldD encoding lactate dehydrogenases. LdhA is responsible
      for production of L-lactate, while LldD is for its assimilation. Since L-lactate
      production was observed as a by-product of glutamate production under biotin
      limited conditions, LldR might play a regulatory role in the glutamate
      metabolism. Here for the first time, we investigated effects of overproduction or
      deletion of LldR on the glutamate metabolism under biotin-limited conditions in
      C. glutamicum. It was found that glutamate production under biotin-limited
      conditions was decreased by overproduction of LldR. In the wild-type cells, L
      lactate was produced in the first 24 h and it was re-consumed thereafter. On the
      other hand, in the overproduced cells, L-lactate was produced like the wild type,
      but it was not re-consumed. This means that L-lactate assimilation, which is
      catalyzed by LldD, was suppressed by the overproduction of LldR, but L-lactate
      production, which is catalyzed by LdhA, was not affected, indicating that LldR
      mainly controls the expression of lldD but not of ldhA under biotin-limited
      conditions. This was confirmed by quantitative real-time RT-PCR. From these
      results, it is suggested that L-lactate metabolism, which is controlled by LldR,
      has a buffering function of the pyruvate pool for glutamate production.

PMID- 23863293
TI  - Identification of the sulphate ion as one of the key components of yeast spoilage
      of a sports drink through genome-wide expression analysis.
AB  - Because of the growing market for sports drinks, prevention of yeast
      contamination of these beverages is of significant concern. This research was
      performed to achieve insight into the physiology of yeast growing in sports
      drinks through a genome-wide approach to prevent microbial spoilage of sports
      drinks. The genome-wide gene expression profile of Saccharomyces cerevisiae
      growing in the representative sports drink was investigated. Genes that were
      relevant to sulphate ion starvation response were upregulated in the yeast cells
      growing in the drink. These results suggest that yeast cells are suffering from
      deficiency of extracellular sulphate ions during growth in the sports drink.
      Indeed, the concentration of sulphate ions was far lower in the sports drink than
      in a medium that allows the optimal growth of yeast. To prove the starvation of
      sulphate ions of yeast, several ions were added to the beverage and its effects
      were investigated. The addition of sulphate ions, but not chloride ions or sodium
      ions, to the beverage stimulated yeast growth in the beverage in a dose-dependent
      manner. Moreover, the addition of sulphate ions to the sports drink increased the
      biosynthesis of sulphur-containing amino acids in yeast cells and hydrogen
      sulphide in the beverage. These results indicate that sulphate ion concentration
      should be regulated to prevent microbial spoilage of sports drinks. 

PMID- 23863292
TI  - Phenotypic and phylogenetic characterization of an abamectin-degrading bacterial
      strain isolated from a citrus orchard.
AB  - Bacterial strain GB-01 was isolated from abamectin-contaminated soils by
      continuous enrichment culture. The preliminary identification of strain GB-01 as
      a Burkholderia species was based mainly on simple biochemical and substrate
      utilization tests; however, these tests alone cannot accurately differentiate all
      the species within the genus Burkholderia. The strain GB-01 was subjected to
      taxonomic analysis through a polyphasic approach, in which phenotypic, genotypic,
      and phylogenetic information was gathered to conclude the classification of this
      microbe. Phenotypic information comes from basic bacteriological tests and
      substrate utilization patterns using the Biolog GN2 MicroPlating system and
      automated miniature biochemical test kits, i.e. API 20 NE, ID 32 GN and API 50
      CH, as well as analyzing the whole cell fatty acid profile. Genotypic information
      was gathered from whole genome DNA base composition (G+C mol%), and DNA-DNA
      hybridization with its closest species, while phylogenetic information was
      collected from the comparative analysis of 16S rRNA and recA gene sequences. The
      results of polyphasic analysis concluded that strain GB-01 is an atypical strain
      of the Burkholderia diffusa species.

PMID- 23863294
TI  - Salmonella enterica serovar Typhi cutF is upregulated during environmental
      stress.

PMID- 23863295
TI  - Porphyrobacter colymbi sp. nov. isolated from swimming pool water in Tokyo,
      Japan.

PMID- 23863296
TI  - Identification and characterization of four bacterial strains isolated from a
      bioaugmented sequencing batch reactor.

PMID- 23863297
TI  - Construction of a ligD disruptant for efficient gene targeting in white koji
      mold, Aspergillus kawachii.

PMID- 23863298
TI  - Mold cleaning with polydimethylsiloxane for nanoimprint lithography.
AB  - We present a simple and effective mold cleaning method for nanoimprint
      lithography. Polydimethylsiloxane (PDMS) prepolymer is spin-coated onto a
      contaminated imprint mold, thermally cured in an ambient environment, and then
      peeled off afterwards. Contaminants of 100 s MUm to sub-50 nm sizes are
      effectively cleaned within one cycle. During the cleaning process, a very thin
      PDMS film (1-2 nm) is uniformly coated onto the mold surface, serving as a
      protection and anti-sticking layer. 

PMID- 23863299
TI  - Successful long-term intermittent hemodialysis in a patient with left ventricular
      assist device.
AB  - Renal impairment is a frequent complication of cardio-renal syndrome that
      increases mortality and morbidity. This is even more likely when renal
      replacement therapy is required, precluding in many cases transplantation and
      seriously limiting life expectancy. We describe the first case of refractory
      heart failure in a patient with a ventricular assist device (LVAD) implanted as
      destination therapy. He underwent intermittent hemodialysis (HD) treatment as an
      outpatient with good quality of life. 

PMID- 23863304
TI  - The reliability of a 30-s sprint test on the Wattbike cycle ergometer.
AB  - PURPOSE: To determine the reliability of a 30-s sprint cycle test on the Wattbike
      cycle ergometer. METHODS: Over 3 consecutive weeks, 11 highly trained cyclists
      (mean +/- SD; age 31 +/- 6 y, mass 74.6 +/- 10.6 kg, height 180.5 +/- 8.1cm)
      completed four 30-s maximal sprints on a Wattbike ergometer after a standardized
      warm-up. The sprint test implemented a "rolling start" that consisted of a 60-s
      preload (at an intensity of 4.5 W/kg) before the 30-s maximal sprint. Variables
      determined across the duration of the sprint were peak power (Wpeak), mean power
      (Wmean), W/kg, mean cadence (rpm), maximum heart rate (n = 10), and postexercise
      blood lactate. RESULTS: The average intraclass correlation coefficients between
      trials (2v1, 3v2, 4v3, 4v1) were Wpeak .97 (90%CI .94-.99), Wmean .99 (90%CI .97
      1.00), W/kg .96 (90%CI .91-.98), mean cadence .96 (90%CI .92-.99), maximum heart
      rate .99 (90%CI .97-.99), and postexercise blood lactate .94 (90%CI .87-.98). The
      average typical error of measurement (expressed as a CV% and absolute value
      between trials-2v1, 3v2, 4v3, 4v1) was Wpeak 4.9%, 52.7 W; Wmean 2.4%, 19.2 W;
      W/kg 2.3%, 0.18 W/kg; mean cadence 1.4%, 1.6 rpm; maximum heart rate 0.9%, 1.6
      beats/min; and postexercise blood lactate 4.6%, 0.48 mmol/L. CONCLUSION: A 30-s
      sprint test on the Wattbike cycle ergometer is highly reproducible in trained
      cyclists.

PMID- 23863312
TI  - The overcorrected clubfoot in the adult: evaluation and management--topical
      review.

PMID- 23863313
TI  - Proximal oblique sliding closing wedge osteotomy for hallux valgus.
AB  - BACKGROUND: The proximal oblique sliding closing wedge osteotomy (POSCOW)
      technique was developed to address moderate to severe hallux valgus deformity. We
      present a retrospective multicenter study to analyze the midterm radiological and
      clinical outcomes of patients treated with this type of proximal osteotomy fixed
      with plates. MATERIALS AND METHODS: One hundred and forty-four patients (187
      feet) were operated on between May 2005 and June 2010 in 2 separate centers.
      Inclusion criteria were symptomatic moderate to severe incongruent hallux valgus
      deformity, no significant restriction in the first metatarsophalangeal joint
      movement, none to minimal degenerative changes in the first metatarsophalangeal
      or the tarsometatarsal joints, and no hypermobility. The median age was 60 years.
      The preoperative hallux valgus angle (HV) was 35.6 degrees, intermetatarsal angle
      (IM) was 15.3 degrees, AOFAS score was 53 points. The median follow-up was 35
      months (range, 12-73). A POSCOW osteotomy was performed in all patients and fixed
      with plates. We recorded the satisfaction rate, postoperative clinical and
      radiological results, and complications. RESULTS: The patient satisfaction rate
      was 87%. The mean postoperative HV angle was 12.3 degrees, IM angle 4.8 degrees,
      AOFAS score 89 points. The mean decrease in the first metatarsal length was 2.2
      mm (range, 0-8). Twelve feet (6.4%) with recurrence of the deformity required
      revision surgeries. Removal of complete or partial hardware was needed in 23 feet
      (12.3%) for symptomatic hardware. Five feet (2.6%) developed hallux varus but
      only 2 required surgery. Transfer metatarsalgia was noted in 9 feet (4.8%).
      CONCLUSIONS: The POSCOW osteotomy was an effective and reliable method for
      relieving pain and improving function. A learning curve was present, as most of
      the complications happened in the initial cases. To our knowledge, this is the
      largest reported series of proximal closing wedge osteotomy for hallux valgus
      deformities. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 23863314
TI  - A combination of in vitro comet assay and micronucleus test using human
      lymphoblastoid TK6 cells.
AB  - The comet assay has been widely used as a genotoxicity test for detecting primary
      DNA damage in individual cells. The micronucleus (MN) test is also a well
      established assay for detecting clastogenicity and aneugenicity. A combination of
      the comet assay (COM) and MN test is capable of detecting a variety of genotoxic
      potentials as an in vitro screening system. Although the in vitro MN test has a
      robust protocol and Organisation for Economic Co-operation and Development (OECD)
      test guideline, the in vitro COM does not. To establish a robust protocol for the
      COM and to compare its sensitivity with that of the MN, we conducted COM and MN
      concurrently for five genotoxic agents (ethyl methanesulfonate, methyl
      methanesulfonate, hydrogen peroxide, gamma-rays and mitomycin C) and one non
      genotoxic agent (triton X-100), using human lymphoblastoid TK6 cells. Relative
      cell count (RCC), relative population doubling (RPD), relative increase in cell
      count (RICC) and relative cell viability determined by trypan blue dye-exclusion
      assay (TBDE) were employed as cytotoxic measurements. However, the relative cell
      viability determined by TBDE just after the treatment was not an appropriate
      parameter of cytotoxicity for the genotoxic agents because it remained constant
      even at the highest doses, which showed severe cytotoxicity by RCC, RPD and RICC.
      The results of the COM showed qualitative agreement (positive or negative) with
      those of the MN except for mitomycin C, which is an interstrand cross-linker. The
      COM always required higher doses than the MN to detect the genotoxic potential of
      the genotoxic agents under the test conditions applied here. The doses that
      induced a comet tail always yielded <50% RICC, and do not accord to the OECD test
      guideline for MN because of their high cytotoxicity. These results are helpful
      for interpreting the results of the COM and MN in in vitro genotoxic hazard
      assessments. Further investigation is required to standardise the COM. 

PMID- 23863316
TI  - Coronary ectasia: manifesting as acute coronary syndrome.

PMID- 23863315
TI  - The effect of aging on acetaminophen pharmacokinetics, toxicity and Nrf2 in
      Fischer 344 rats.
AB  - We investigated the effect of aging on hepatic pharmacokinetics and the degree of
      hepatotoxicity following a toxic dose of acetaminophen. Young and old male
      Fischer 344 rats were treated with 800 mg/kg acetaminophen (young n = 8, old n =
      5) or saline (young n = 9, old n = 9). Serum measurements showed old rats treated
      with acetaminophen had significantly lower serum alanine aminotransferase and
      higher acetaminophen and acetaminophen glucuronide levels and creatinine,
      compared with acetaminophen treated young rats (p < .05). Immunoblotting and
      activity assays showed old saline-treated rats had twofold lower cytochrome P450
      2E1 activity and threefold higher NAD(P)H quinone oxireductase 1 protein
      expression and activity than young saline-treated rats (p < .05), although Nrf2,
      glutathione cysteine ligase-modulatory subunit, glutathione cysteine ligase
      catalytic subunit, and cytochrome P450 2E1 protein expressions were unchanged.
      Primary hepatocytes isolated from young rats treated with 10 mM acetaminophen had
      lower survival than those from old rats (52.4% +/- 5.8%, young; 83.6% +/- 1.7%,
      old, p < .05). The pharmacokinetic changes described may decrease susceptibility
      to acetaminophen-induced hepatotoxicity but may increase risk of nephrotoxicity
      in old age. 

PMID- 23863317
TI  - Effects of ACE and ADD1 gene polymorphisms on blood pressure response to
      hydrochlorothiazide: a meta-analysis.
AB  - Hydrochlorothiazide (HCTZ) is used to treat uncomplicated hypertension. However,
      many studies have reported the variance of inter-individual response to HCTZ. A
      meta-analysis of published data was conducted to evaluate the pharmacogenetic
      associations of ACE I/D and ADD1 Gly460Trp polymorphisms with blood pressure
      changes during HCTZ therapy. To analyze the influence of ACE I/D polymorphism, 4
      studies including 1,439 patients were assessed and the 3 genotypes were compared
      (II vs. ID, II vs. DD, and ID vs. DD) with respect to blood pressure changes. A
      significant association between ACE and blood pressure change was observed for
      the comparison of the II and DD (standard differences in means = 0.256; 95% CI,
      0.109 - 0.403). For ADD1 Gly460Trp polymorphism, 4 studies including 1,001
      patients were assessed, and GlyGly vs. GlyTrp, GlyGly vs. TrpTrp and GlyTrp vs.
      TrpTrp genotype comparisons were analyzed. A significant association between ADD1
      and blood pressure change was observed for the comparisons of GlyGly vs. GlyTrp
      (standard differences in means= 2.78; 95% CI, 0.563 - 4.99) and GlyGly vs. TrpTrp
      (standard differences in means = 1.80; 95% CI, 1.38 - 2.22). This study is the
      first meta-analysis to evaluate the influences of ACE and ADD1 polymorphisms on
      blood pressure responses to HCTZ to combine the inconsistent results of previous
      studies. 

PMID- 23863322
TI  - Genome-wide identification of genes regulated in trans by transposable element
      small interfering RNAs.
AB  - Transposable elements (TEs) are known to influence the regulation of neighboring
      genes through a variety of mechanisms. Additionally, it was recently discovered
      that TEs can regulate non-neighboring genes through the trans-acting nature of
      small interfering RNAs (siRNAs). When the epigenetic repression of TEs is lost,
      TEs become transcriptionally active, and the host cell acts to repress mutagenic
      transposition by degrading TE mRNAs into siRNAs. In this study, we have performed
      a genome-wide analysis in the model plant Arabidopsis thaliana and found that TE
      siRNA-based regulation of genic mRNAs is more pervasive than the two formerly
      characterized proof-of-principle examples. We identified 27 candidate genic mRNAs
      that do not contain a TE fragment but are regulated through partial
      complementarity by the accumulation of TE siRNAs and are therefore influenced by
      TE epigenetic activation. We have experimentally confirmed several gene targets
      and demonstrated that they respond to the accumulation of specific 21 nucleotide
      TE siRNAs that are incorporated into the Arabidopsis Argonaute1 protein.
      Additionally, we found that one TE siRNA specifically targets and inhibits the
      formation of a host protein that acts to repress TE activity, suggesting that TEs
      harbor and potentially evolutionarily select short sequences to act as
      suppressors of host TE repression. 

PMID- 23863323
TI  - Cognitive test scores in young men and subsequent risk of type 2 diabetes,
      cardiovascular morbidity, and death.
AB  - BACKGROUND: The association between cognitive scores in young adulthood and long
      term cardiometabolic risks remains unclear. METHODS: Using population-based
      registries, we followed 6502 military conscripts from their 22nd birthday until
      death, emigration, or 55 years of age. We calculated risks and hazard ratios
      (HRs) associating quartiles of cognitive scores (very high, high, moderate, and
      low) with type 2 diabetes, hypertension, myocardial infarction, stroke, venous
      thromboembolism, and death before age 55 years. RESULTS: The 33-year risk of the
      combined outcome was inversely associated with cognitive scores (26% for low and
      16% for very high scores). Compared with very high scores, the HR for the
      combined outcome was 1.20 (95% confidence interval = 1.02, 1.41) for high, 1.43
      (1.22, 1.68) for moderate, and 1.67 (1.43, 1.95) for low scores. Similar HRs were
      observed for individual outcomes. CONCLUSION: Low cognitive score in young
      adulthood was a strong predictor for type 2 diabetes, cardiovascular morbidity,
      and death before 55 years of age.

PMID- 23863324
TI  - How to explain the discordant change of ulcerative colitis and Crohn disease in
      adjacent or even the same regions and time periods.

PMID- 23863325
TI  - Epidemiology of coeliac disease and comorbidity in Norwegian children.
AB  - OBJECTIVES: The aim of this study was to describe the occurrence of clinically
      diagnosed coeliac disease in children ages 0 to 12 years in Norway, including
      regional variation and coexisting type 1 diabetes mellitus, thyroid disease, and
      Down syndrome. METHODS: The Norwegian Patient Register (NPR) contains individual
      level hospital data from 2008 onward. Small-bowel biopsies for establishing the
      coeliac disease diagnosis are only performed at public hospitals reporting to the
      NPR. Data on all hospital contacts during 2008-2011 when a diagnosis of coeliac
      disease was registered were retrieved from the NPR for patients born between 1999
      and 2011, allowing estimation of the proportion registered with coeliac disease
      at ages 0 to 12 years in a cohort study. RESULTS: A total of 3006 individuals
      (58.2% girls) were recorded as having coeliac disease among 797,360 children,
      corresponding to a proportion of 3.8/1000 (95% confidence interval [CI] 3.7
      3.9/1000) children, 4.5 (CI 4.3-4.7) among girls and 3.1 (CI 2.9-3.3/1000) among
      boys (P < 0.001). The proportion increased with age up to approximately 6 years
      and was 5.0/1000 (CI 4.5-5.6) at the age of 12 years, and was slightly higher in
      the south/west (3.9/1000) as compared to the middle/north (3.5/1000) regions of
      Norway (P = 0.013). A total of 214 of 3006 (7.1%) patients with coeliac disease
      were registered with coexisting conditions: type 1 diabetes mellitus (n = 142,
      4.7%), Down syndrome (n = 47, 1.6%), or thyroid disease (n = 41, 1.4%).
      CONCLUSIONS: In this first nationwide study of clinically diagnosed coeliac
      disease in Norwegian children, we found a high occurrence, comparable with that
      in Sweden. Comorbidity was common, but routine screening of high-risk groups
      contributed to a limited number of cases.

PMID- 23863326
TI  - Case finding for celiac disease is okay, but is it enough?

PMID- 23863327
TI  - Graduate medical education in humanism and professionalism: a needs assessment
      survey of pediatric gastroenterology fellows.
AB  - The deterioration of humanism and professionalism during graduate medical
      training is an acknowledged concern, and programs are required to provide
      professionalism education for pediatric fellows. We conducted a needs assessment
      survey in a national sample of 138 first- and second-year gastroenterology
      fellows (82% response rate). Most believed that present humanism and
      professionalism education met their needs, but this education was largely
      informal (eg, role modeling). Areas for formal education desired by >70% included
      competing demands of clinical practice versus research, difficult doctor-patient
      relationships, depression/burnout, angry parents, medical errors, work-life
      balance, and the patient illness experience. These results may guide curricula to
      formalize humanism and professionalism education in pediatric gastroenterology
      fellowships. 

PMID- 23863328
TI  - Efficacy and safety of rabeprazole in children (1-11 years) with gastroesophageal
      reflux disease.
AB  - OBJECTIVE: Evaluate the efficacy and safety of rabeprazole in children, 1 to 11
      years old, with endoscopically/histologically proven gastroesophageal reflux
      disease (GERD). METHODS: Children were randomized to 0.5- or 1.0-mg/kg
      rabeprazole granule formulation for 12 weeks. The dose was further determined by
      weight: children 6 to 14.9 kg (low-weight cohort) received 5 or 10 mg and
      children >=15 kg (high-weight cohort) received 10 or 20 mg. The primary endpoint
      was endoscopic/histologic healing at week 12 (defined as grade 0 on the Hetzel
      Dent classification scale and/or grade 0 on the Histological Features of Reflux
      Esophagitis scale). RESULTS: Overall, 81% (87/108) achieved endoscopic/histologic
      healing at week 12 with higher healing in the low-weight cohort (82% [5-mg dose],
      94% [10-mg dose]) compared with high-weight cohort (76% [10-mg dose], 78% [20-mg
      dose]). There was a significant (P < 0.001) decrease in the mean Total GERD
      Symptoms and Severity score from 19.7 points (baseline) to 8.6 points (week 12),
      with 26% fewer children reporting GERD symptoms at week 12. The average frequency
      of symptoms per child decreased from 7.7 (week 1) to 4.7 (week 12). The GERD
      Symptom Relief score showed that 71% of children felt better, 81% were rated
      "good to excellent" on the Global Treatment Satisfaction scale by the
      investigator; 77% were rated "good to excellent" on the Clinical Global
      Impressions-Improvement scale by the parent/caregiver. The most common (>10%)
      treatment-emergent adverse events included cough and vomiting (14% each),
      abdominal pain (12%), and diarrhea (11%). CONCLUSIONS: Rabeprazole was effective
      and safe in 1- to 11-year-old children with GERD.

PMID- 23863329
TI  - Hypoalbuminemia and ascites in a patient with alpha1-antitrypsin deficiency: time
      for a gut check.

PMID- 23863330
TI  - Generation and characterization of a new solid form of trehalose.
AB  - We have identified and characterized a new solid form of trehalose, the delta
      form (Tdelta) using (13)C solid-state NMR spectroscopy (SSNMR). Tdelta is formed
      from dehydrations of trehalose dihydrate (T(h)) performed at or below 100 
      degrees C, and it is generated concurrently with the alpha form of trehalose
      (Talpha) and amorphous trehalose (T(am)); the beta form of trehalose (Tbeta) has
      been observed in some dehydrated samples. Differential scanning calorimetry (DSC)
      and powder X-ray diffraction (PXRD) studies of samples containing Tdelta do not
      indicate the presence of the new form. Tdelta is metastable: upon exposure to
      temperatures above 80  degrees C, it converts to either Talpha or Tam, and upon
      exposure to ambient humidity, it reverts to T(h).

PMID- 23863331
TI  - Gold nanocrescents for remotely measuring and controlling local temperature.
AB  - We present a novel technique to remotely measure and control the local
      temperature within a medium. This technique is based on the observation of the
      rotational Brownian motion of gold nanocrescent particles, which possess a strong
      anisotropic light interaction due to their plasmonic properties. Rotational
      scattering correlation spectroscopy performed on a single nanoparticle is able to
      determine the local temperature with high accuracy. These nano-thermometers can
      simultaneously play the role of nano-heaters when absorbing the light of a
      focused laser beam. 

PMID- 23863332
TI  - Antiplasmodial sesquiterpenes from the seeds of Salacia longipes var.
      camerunensis.
AB  - Phytochemical investigation of the seeds of Salacia longipes var. camerunensis
      led to the isolation of four sesquiterpenoid derivatives, salaterpene A (1)
      (1alpha,2beta,8beta-triacetoxy-6beta,9beta-dibenzoyloxy-4beta-hydroxy-dihydro
      beta-agarofuran), salaterpene B (2) (1alpha,2beta,8beta-triacetoxy-9beta
      benzoyloxy-6beta-cinnamoyloxy-4beta-hydroxy-dihydro-beta-agarofuran), salaterpene
      C (3) (1alpha,2beta-diacetoxy-6beta,9beta-dibenzoyloxy-4beta-hydroxy-dihydro-beta
      agarofuran) and salaterpene D (4) (2beta-acetoxy-1alpha,6beta-dibenzoyloxy-4beta
      hydroxy-9beta-nicotinoyloxy-dihydro-beta-agarofuran) together with two known
      compounds (5 and 6). The structures of the compounds were established by means of
      NMR spectroscopy. Compounds 1-4 and 6 were tested in vitro for their
      antiplasmodial activity against Plasmodium falciparum chloroquine-resistant
      strain W2. All the tested compounds exhibited a moderate potency with IC50 below
      2.7 MUM.

PMID- 23863333
TI  - Air pollution irreversibly impairs lung function: a twenty-year follow-up of
      officially acknowledged victims in Japan.
AB  - Lung function is one of the strongest determinants of cardiopulmonary health and
      longevity. Long-term exposure to air pollution has been associated with decreased
      lung function. We undertook a retrospective study to compare the long-term
      consequences of air pollution in two areas of Japan: Mizushima, Okayama
      Prefecture and Kitakyushu, Fukuoka Prefecture. Industrialization began in
      Mizushima in the 1940s, whereas it began in Kitakyushu in the early 1900s. In
      Kitakyushu, levels of nitrogen dioxide have been higher compared to the Mizushima
      area. The subjects comprised 623 officially acknowledged victims of pollution
      related illness (489 from Mizushima and 134 from Kitakyushu). All subjects were
      lifetime non-smokers and aged 65 years or older at the time of their last medical
      examination in 2009. Demographic data including diagnosed lung diseases and lung
      function at the time of certification assessment performed between 1973 and 1988
      were obtained. The subjects from Kitakyushu were significantly younger (47.1 vs.
      51.0 years, p < 0.001) and a higher percentage had asthma (91.2 vs. 36.8%, p <
      0.001) compared to those from Mizushima. Furthermore, all measures of lung
      function were significantly lower in Kitakyushu group at the time of the
      certification assessment (p < 0.001) and at the follow-up (p < 0.001). However,
      no significant differences were observed in the annual mean decline in lung
      function between the two groups, despite the overall decrease in air pollution.
      In conclusion, the normal lung function is not restored even after improvement of
      air pollution. It is essential for every city to prevent air pollution. 

PMID- 23863334
TI  - Bottom-up and top-down attention are independent.
AB  - What is the relationship between top-down and bottom-up attention? Are both types
      of attention tightly interconnected, or are they independent? We investigated
      this by testing a large representative sample of the Dutch population on two
      attentional tasks: a visual search task gauging the efficiency of top-down
      attention and a singleton capture task gauging bottom-up attention. On both tasks
      we found typical performance--i.e., participants displayed a significant search
      slope on the search task and significant slowing caused by the unique, but
      irrelevant, object on the capture task. Moreover, the high levels of significance
      we observed indicate that the current set-up provided very high signal to noise
      ratios, and thus enough power to accurately unveil existing effects. Importantly,
      in this robust investigation we did not observe any correlation in performance
      between tasks. The use of Bayesian statistics strongly confirmed that performance
      on both tasks was uncorrelated. We argue that the current results suggest that
      there are two attentional systems that operate independently. We hypothesize that
      this may have implications beyond our understanding of attention. For instance,
      it may be that attention and consciousness are intertwined differently for top
      down attention than for bottom-up attention.

PMID- 23863335
TI  - Distinguishing between target and nontarget fixations in a visual search task
      using fixation-related potentials.
AB  - The P300 event-related potential (ERP) can be used to infer whether an observer
      is looking at a target or not. Common practice in P300 experiments and
      applications is that observers are asked to fixate their eyes while stimuli are
      presented. We investigated the possibility to differentiate between single target
      and nontarget fixations in a target search task involving eye movements by using
      EEG epochs synchronized to fixation onset (fixation-related potentials: FRPs).
      Participants systematically scanned search displays consisting of six small
      Landolt Cs in search of Cs with a particular orientation. After each search
      display, they indicated whether and where target Cs had been presented. As
      expected, an FRP component consistent with the P300 reliably distinguished
      between target and nontarget fixations. It was possible to classify single FRPs
      into target and nontarget FRPs above chance (on average 62% correct, where 50%
      would be chance). These results are the first step to practical applications such
      as covertly monitoring observers' interests and supporting search tasks. 

PMID- 23863340
TI  - Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in
      mouse model of dilated cardiomyopathy with troponin T deletion mutation
      DeltaK210.
AB  - It has been reported that the Frank-Starling mechanism is coordinately regulated
      in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice
      spacing changes. In the present study, we tested the hypothesis that the deletion
      mutation DeltaK210 in the cardiac troponin T gene shifts the equilibrium toward
      the "off" state and accordingly attenuate the sarcomere length (SL) dependence of
      active force production, via reduced cross-bridge formation. Confocal imaging in
      isolated hearts revealed that the cardiomyocytes were enlarged, especially in the
      longitudinal direction, in DeltaK210 hearts, with striation patterns similar to
      those in wild type (WT) hearts, suggesting that the number of sarcomeres is
      increased in cardiomyocytes but the sarcomere length remains unaltered. For
      analysis of the SL dependence of active force, skinned muscle preparations were
      obtained from the left ventricle of WT and knock-in (DeltaK210) mice. An increase
      in SL from 1.90 to 2.20MUm shifted the mid-point (pCa50) of the force-pCa curve
      leftward by ~0.21pCa units in WT preparations. In DeltaK210 muscles, Ca(2+)
      sensitivity was lower by ~0.37pCa units, and the SL-dependent shift of pCa50,
      i.e., DeltapCa50, was less pronounced (~0.11pCa units), with and without protein
      kinase A treatment. The rate of active force redevelopment was lower in DeltaK210
      preparations than in WT preparations, showing blunted thin filament cooperative
      activation. An increase in thin filament cooperative activation upon an increase
      in the fraction of strongly bound cross-bridges by MgADP increased DeltapCa50 to
      ~0.21pCa units. The depressed Frank-Starling mechanism in DeltaK210 hearts is the
      result of a reduction in thin filament cooperative activation. 

PMID- 23863341
TI  - A case of cohesinopathy with a novel de-novo SMC1A splice site mutation.

PMID- 23863342
TI  - A case of Filippi syndrome with atypical limb defects in a 3-year-old boy and a
      review of the literature.

PMID- 23863343
TI  - Gliosarcoma with ependymal and PNET-like differentiation.
AB  - A rare case of gliosarcoma which arose in the temporal lobe of a 39-yearold man
      was reported. The gliomatous area of the tumor showed ependymal differentiation,
      and also contained immature neuroectodermal tissue resembling a primitive
      neuroectodermal tumor (PNET) in addition to an ordinary glioblastomatous
      component. Tumor cells in the PNET-like component were immunoreactive for
      synaptophysin, CD99, neurogenin 3, and alpha-internexin, but not for glial
      fibrillary acidic protein (GFAP), Class III-beta tubulin, or Neu N. The
      mesenchymal area exhibited a compact fascicular proliferation of atypical spindle
      cells invested by fine reticulin fibrils. In addition, these cells were
      immunoreactive for Slug and Twist - transcription factors which are involved in
      the "epithelial-mesenchymal transition (EMT)" phenomenon. Gliosarcomas containing
      an ependymal or PNET-like component are rare, and to our knowledge, the present
      case is the first to be reported whose glial element exhibited differentiation
      toward these two components. The diverse differentiation in the glial element
      suggests that the tumor most likely originated from primitive neuroepithelial
      progenitor cells rather than from the neometaplasia of a glioblastoma. The
      immunoreactivity for transcription factors in the mesenchymal element indicated
      that EMT might be involved in the pathogenesis of this very rare type of
      gliosarcoma. 

PMID- 23863344
TI  - Embryonal tumor with multilayered rosettes: diagnostic tools update and review of
      the literature.
AB  - Embryonal tumor with multilayered rosettes (ETMR), including embryonal tumor with
      abundant neuropil and true rosettes (ETANTR), and ependymoblastoma (EBL)
      constitute a distinct entity of the primitive neuroectodermal tumor (PNET)
      family. The presence of a focal amplification at chromosome region 19q13.42
      associated with an up-regulation of the oncogenic miRNA cluster C19MC suggests
      that they may represent a histological spectrum of a single biological entity.
      Their histopathological spectrum is wide, including medulloepithelioma, their
      location may be supra- or infra-tentorial, their prognosis is poor. Recent data
      on molecular subgroups of PNETs have led to new insights on diagnosis and
      treatment of these tumors. Subsequently, LIN28A immunoexpression was identified
      as a highly specific marker for ETMR. In this study, we report 4 cases diagnosed
      initially as ETANTR with CGH-array data, including 19q13.42 gain with absence of
      other amplicons, particularly of the MYC gene family, and inconstant gain of
      whole chromosome 2. Immunohistochemical positive expression of LIN28A and absence
      of Olig2 expression were observed. We summarize the literature on ETMR, pointing
      out on the nosological evolution of this entity and the findings on genetic
      hallmarks of this particular tumor. Our results emphasize the usefulness of
      immunohistochemistry as a highly sensitive and fast diagnostic tool for ETMR and
      for genetic data, especially for 19q13.42 locus. Biological features may offer
      new therapeutic options for these embryonal tumors that do not usually respond to
      conventional treatments of PNETs. 

PMID- 23863345
TI  - Plaque-like demyelination in acute disseminated encephalomyelitis (ADEM) - an
      autopsy case report.
AB  - AIMS/BACKGROUND: The pattern of demyelination in the scant autopsy literature on
      acute disseminated encephalomyelitis (ADEM) is described as perivenous sleeves.
      We report an unusual neuropathological presentation of ADEM, also known as
      postinfectious or perivenous encephalomyelitis. CASE HISTORY: A 19-yearold female
      patient presented with headache and myalgias, followed by subacute onset of
      lethargy, confusion, left hemiparesis and dysphasia after an interval of 4 - 5
      days. On MRI, extensive subcortical white matter lesions were seen and a
      diagnosis of ADEM was made after other causes were excluded. The patient received
      intravenous methylprednisolone and plasma exchange. Neurological symptoms
      remained stable over the length of the hospital stay (1 month). The patient
      passed away due to non-neurologic causes. RESULTS: On autopsy, the brain showed
      extensive, confluent, plaque-like demyelinating lesions with a striking
      selectivity for the subcortical white matter sparing the U-fibers. No lesions
      were discernible in the cortex, the deep grey matter, the cerebellum, the spinal
      cord or the optic nerves on LFB-stained sections. Only one lesion extended to the
      periventricular area in the right occipital lobe. Some lesions had a scalloped
      border and foci of inhomogeneous demyelination, suggestion coalescence of smaller
      lesions. Histologically, all lesions were of the same age, coupling near complete
      demyelination with relative preservation of axons, along with scant perivascular
      lymphohistiocytic cuffing, dense infiltration by foamy macrophages, and prominent
      gliosis. CONCLUSION: The morphology of individual demyelinating< lesions is
      indistinguishable from the lesions in a new onset case of multiple sclerosis (MS)
      and adds to the autopsy literature on overlapping neuropathological findings in
      ADEM and multiple sclerosis.

PMID- 23863346
TI  - Normal pressure hydrocephalus mimicking Alzheimer's disease: such an infrequent
      case?
AB  - Normal pressure hydrocephalus (NPH) is an age-related condition frequently
      associated with degenerative and vascular brain pathologies. However, cases of
      NPH with no concomitant brain pathology have been described with important
      implications in terms of early detection and treatment. We present a case of NPH
      that commenced with cognitive deterioration similar to Alzheimer's disease (AD).
      Motor manifestations (i.e., falls and gait dysfunction) appeared 2.5 years after
      the initiation of memory problems. Apart from ventricular enlarging, no prominent
      pathologies were found at brain examination. The prevalence of cases of NPH
      presenting with memory problems may be underestimated given the traditional view
      of NPH displaying a clinical triad of gait dysfunction, mental decline of
      "subcortical" appearance, and incontinence. Careful examination of the structural
      neuroimaging study in the initial assessment and during follow-up could help in
      diagnosis. Further research on prevalence and detection of "pure" NPH initially
      resembling AD is warranted. 

PMID- 23863347
TI  - Calcifying pseudoneoplasm of the neuraxis overlying the corpus callosum: a case
      report and review of the literature.
AB  - Calcifying pseudoneoplasms of the neuraxis (CPN), also known as fibroosseous
      lesions, are slow-growing lesions that can occur in a variety of regions of the
      central nervous system (CNS). These lesions are especially rare, with no more
      than 30 intracranial cases reported in the literature. Due to its non
      malignant/non-metastatic course, one can expect an excellent prognosis with a
      successful complete resection. However, depending on the location of presentation
      within the CNS, CPN can present unique challenges in diagnosis and subsequently,
      the treatment course undertaken. We present a case of an intracranial, extra
      axial CPN in a 49-year-old woman, the second to be reported in this location ever
      and first in 30 years, and detail the clinical, histopathologic and radiological
      features of a CPN along with a review of the literature. 

PMID- 23863348
TI  - GM in the media: a look at the news from around the world on genetically modified
      food and crops.

PMID- 23863349
TI  - Langer's mesomelic dysplasia: a case report.
AB  - Langer's mesomelic dysplasia is a rare cause of disproportionate dwarfism. The
      affected children have a normal intellect and life span and are usually seen
      later in life for management of skeletal deformities. The diagnosis is usually
      established on clinical and anthropometric analyses supported with relevant
      radiological investigations. Plain radiographs and full-length scanograms are
      sufficient in establishing the diagnosis. Further genetic studies are sometimes
      performed for confirmation, as Leri Weill dyschondrosteosis and Langer's
      mesomelic dysplasia are inherited because of mutations in the short stature
      homeobox (SHOX) gene. The literature is sparse with less than a hundred cases
      reported, and this case adds to the available data on this rare syndrome. 

PMID- 23863350
TI  - Comparison of soft-tissue and bone surgeries in the treatment of developmental
      dysplasia of the hip in 18-24-month-old patients.
AB  - The aim of this study was to compare soft-tissue and bone surgeries in 18-24
      month-old patients with developmental dysplasia of the hip (DDH). A total of 77
      hips of 53 patients were analyzed. Soft-tissue surgery was performed in 31 hips
      of 25 patients. In the final examination, 23 hips, excluding hips of eight
      patients who underwent secondary bone surgery, were evaluated (group I). Bone
      surgery was performed on 46 hips of 28 patients (group II). In group I, the
      acetabular index was 41 degrees  preoperatively and was 20.4 degrees  in the
      final examinations. In group II, the acetabular index was 42 degrees 
      preoperatively and was 15 degrees  in the final examinations. To avoid
      unnecessary surgeries and complications, soft-tissue surgery should be preferred
      for DDH in 18-24-month-old patients. 

PMID- 23863351
TI  - Transcranial direct current stimulation (tDCS) for sleep disturbances and fatigue
      in patients with post-polio syndrome.
AB  - PURPOSE: Post-polio syndrome develops about 20-40 years after acute paralytic
      poliomyelitis, and manifests with progressively deteriorating muscle strength and
      endurance. Here, we assessed whether transcranial direct current stimulation
      (tDCS) improves sleep and fatigue symptoms in patients with post-polio syndrome.
      METHODS: We enrolled 32 patients with a diagnosis of post-polio syndrome. tDCS
      (1.5 mA, 15 min) was delivered by a direct current stimulator connected to three
      electrodes: two anodal electrodes on the scalp over the right and left pre-motor
      cortex and the other above the left shoulder (cathode). 16 patients received
      anodal tDCS and the remainder sham tDCS. We evaluated changes induced by tDCS
      (daily for five days a week, for three weeks) on clinical scales (Short Form
      Health Survey [SF-36], Piper Fatigue Scale [PFS], Fatigue Severity Scale [FSS],
      101-Point Numerical Rating [PNR-101], Hamilton Rating Scale for Depression
      [HRSD], Pittsburgh Sleep Quality Index [PSQI]) at baseline (T0) and three weeks
      later (T1). RESULTS: At T1 SF-36 sub-items physical functioning, role physical,
      vitality, social functioning and role emotional improved significantly more in
      patients who received tDCS (p < 0.01) than in sham-treated patients. Also, PSQI
      scores improved more in treated patients (p < 0.05, two-way ANOVA with
      "stimulation" and "time" as factors: p < 0.01). tDCS-induced benefits were more
      pronounced in patients who were younger at primary infection (p < 0.05).
      CONCLUSION: Anodal tDCS over the pre-motor areas for fifteen days improved sleep
      and fatigue symptoms in patients with post-polio syndrome. tDCS could be a non
      invasive and valuable new tool for managing post-polio patients.

PMID- 23863352
TI  - Human serum increases CD4 recycling to plasma membranes of in-vitro cultured
      cells.

PMID- 23863353
TI  - Quantum Hall effect in fractal graphene: growth and properties of graphlocons.
AB  - Highly dendritic graphene crystals up to 0.25 mm in diameter are synthesized by
      low pressure chemical vapor deposition inside a copper enclosure. With their six
      fold symmetry and fractal-like shape, the crystals resemble snowflakes. The
      evolution of the dendritic growth features is investigated for different growth
      conditions, and surface diffusion is found to be the growth-limiting step
      responsible for the formation of dendrites. The electronic properties of the
      dendritic crystals are examined down to sub-Kelvin temperatures, showing a
      mobility of up to 6300 cm(2) V(-1) s(-1) and quantum Hall oscillations are
      observed above 4 T. These results demonstrate the high quality of the transport
      properties despite their rough dendritic edges. 

PMID- 23863354
TI  - A gale of fresh air.

PMID- 23863355
TI  - Application of senofilcon a contact lenses for therapeutic bandage lens
      indications.
AB  - PURPOSE: To conduct a retrospective consecutive chart review of senofilcon A
      contact lenses when used for therapeutic or bandage lens applications. Indication
      for use includes corneal protection from exposure or repeated irritation, corneal
      pain relief, and barrier protection. Outcome assessments included pain relief,
      improvement in corneal signs, additional complications, and overall treatment
      success. METHODS: A total of 43 fully consented patients across 3 different
      clinical practices in the United States (Georgia, Florida and Ohio) were included
      in this study. Subjects enrolled in the study were identified by site
      investigators as their most recent 15 to 20 patients fit in senofilcon A lenses
      for the listed therapeutic indications. The cases were reviewed to assess the
      therapeutic success of the lens for the outcomes listed earlier. RESULTS: All
      lenses fit had an 8.4-mm base curve and 14.0 mm diameter. Patients were fit for
      pain relief in 26 of the 43 cases of which 81% were judged to be fully effective,
      8% partially effective, and 11% ineffective. Improvement in corneal integrity was
      the treatment goal in 25 cases and was fully effective in 64%, partially
      effective in 24%, and no change was noted in 12% of the cases. Twelve refractive
      surgical patients (laser-assisted in situ keratomileusis, epithelial laser
      assisted in situ keratomileusis, laser-assisted subepithelial keratectomy, or
      photorefractive keratectomy) wore the lenses successfully for 4 to 6 days
      postoperatively for comfort and protection without complications. Investigators
      judged the overall treatment as fully successful in 68% cases, partially
      successful in 18% cases, and neutral or unsuccessful in 14% cases. No adverse
      events were reported in any case. CONCLUSIONS: Senofilcon A contact lenses are
      successful in the majority of cases when used for providing protection of corneal
      exposure and recurrent damage, pain management, barrier protection, and
      postsurgical management.

PMID- 23863356
TI  - Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and
      docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian
      cancer.
AB  - OBJECTIVES: The primary objective of this study was to evaluate the safety and
      tolerability of a formulated IL-12 plasmid administered intraperitoneally (IP) in
      conjunction with intravenous (IV) carboplatin/docetaxel in platinum-sensitive
      ovarian cancer patients. METHODS: Escalating doses of IL-12 plasmid (phIL-12)
      formulated with the lipopolymer PEG-PEI-Cholesterol (PPC) were administered IP
      every 10-11 days for a total of four treatments and the highest dose was expanded
      to eight treatments. Patients also received IV carboplatin (AUC 5) and docetaxel
      (75 mg/m(2)) every 21 days. Patients were followed for safety, biological
      activity and antitumor activity after phIL-12/PPC treatment. RESULTS: All 13
      patients enrolled in the study received both phIL-12/PPC and chemotherapy
      treatment. There were 49 plasmid-associated adverse events (AEs). The most common
      AEs were abdominal pain, transient hypotension, low grade fever, catheter site
      pain, chills, dysgeusia, infusion-related reaction, and nausea. These AEs
      appeared to be plasmid dose related. Grade 3 AEs included manageable abdominal
      pain and cytokine release syndrome. There were no dose limiting toxicities and
      the plasmid treatment did not augment the chemotherapy-associated AEs. The best
      overall antitumor response (17% CR, 33% PR, 42% SD and 8% PD) was typical of the
      patient population enrolled for the study. Translational studies showed rise in
      IFN-gamma and TNF-alpha concentrations in a dose dependent manner. CONCLUSIONS:
      The escalating doses and cycles of intraperitoneal phIL-12/PPC when combined with
      carboplatin/docetaxel chemotherapy in recurrent ovarian cancer patients were well
      tolerated and did not appear to exacerbate the side effects or attenuate the
      efficacy of the chemotherapy treatment.

PMID- 23863357
TI  - Surgery for early stage cervical cancer: how radical should it be?
AB  - OBJECTIVE: Less radical or non radical surgery for early-stage cervical cancer
      has been proposed to reduce morbidity while maintaining oncologic outcomes. Given
      that a standardized approach to conservative surgery is not yet available, we
      have summarized the literature on less radical surgery to better inform clinical
      practice. METHODS: MEDLINE R and MEDLINE in-process and non-indexed citations
      were searched from inception to April 14, 2013 to identify all English-language
      articles evaluating less-radical or non radical surgery for invasive cervical
      carcinoma. Articles including patients with squamous cell carcinoma,
      adenocarcinoma and adenosquamous carcinoma were included and a narrative review
      of the literature is presented. RESULTS: Radical surgery is associated with
      significant adverse effects in terms of urinary function, sexual function, and
      body image. Radical trachelectomy is an accepted fertility-sparing option, but
      still leads to morbidity from parametrectomy. The importance of the
      parametrectomy in patients with small early-stage tumors has been questioned
      recently, and many studies have found simple hysterectomy and simple
      trachelectomy can be safe in appropriately selected patients. Cone biopsy may be
      a fertility-sparing option in those patients with a very low risk of parametrial
      involvement. Neoadjuvant chemotherapy is also being investigated as a method to
      reduce the need for radical surgery. Sentinel lymph node biopsy is discussed as a
      method to reduce the morbidity while increasing the sensitivity of pelvic lymph
      node assessment in women with early cervical cancers. Finally, the treatment of
      early adenocarcinoma is addressed. CONCLUSIONS: It appears many women with early
      stage cervical cancer can be treated less radically than has been done in the
      past. Large prospective trials are underway to further define candidates for less
      radical surgery.

PMID- 23863358
TI  - A review of complications associated with the surgical treatment of vulvar
      cancer.
AB  - OBJECTIVE: The mainstay of treatment for most vulvar malignancies is surgery to
      the vulva with lymphadenectomy to the inguino-femoral areas, plus radiotherapy
      or/and chemotherapy for locally advanced, or recurrent disease. Treatment is
      associated with significant physical, sexual, and psychological morbidity. The
      high morbidity rate has resulted in a continuing shift in treatment paradigms
      that focus on treatments that reduce morbidity without compromising cure rates.
      This paper reviews the complications associated with contemporary surgical
      treatment for vulva cancer and discusses preventative strategies. METHODS: A
      review of the English literature was undertaken for articles published between
      1965 and August 31, 2012 to identify articles that assessed complications
      resulting from surgery to the vulva or groins in patients with vulva cancer. Two
      independent researchers selected and qualitatively analyzed the articles using a
      predetermined protocol. RESULTS: The heterogeneity of articles and differences in
      definitions and outcomes made this unsuitable for meta-analysis. Most studies
      advocated for change in surgical technique to reduce complications associated
      with inguino-femoral lymphadenectomy and surgery to the vulva, with varying
      success. The most effective means of preventing complications is by omitting
      systematic lymph node dissection. This can be achieved safely through sentinel
      lymph node biopsy. Saphenous vein sparing, VTE prophylaxis, the use of flaps and
      grafts, and preoperative counseling are additional ways to decrease morbidity.
      CONCLUSION: Despite technical advances, complications following surgical
      treatment for vulva cancer remain high. More research, particularly multi
      centered randomized controlled trials to improve the quality of evidence and
      studies that focus on complications as an outcome measure and analyze individual
      surgeon complication rates, are needed. Measures also need to be standardized
      throughout the gynecologic oncology community to allow for better comparison
      between studies.

PMID- 23863359
TI  - Folate and folate receptor alpha antagonists mechanism of action in ovarian
      cancer.
AB  - OBJECTIVE: The goal of this report is to review the activity of promising
      antifolate and folate receptor agents being developed for ovarian cancer
      including thymidylate synthase inhibitors, antifolate receptor antibodies, and
      folate-chemotherapy conjugates. METHODS: A literature search was performed over
      the last 5 years using the terms "folate receptor" and "ovarian cancer" and those
      that specifically addressed the MOA were included. Abstracts presented within the
      last 3 years were also searched and included in this review where appropriate.
      RESULTS: Thymidylate synthase inhibitors are a promising avenue for ovarian
      cancer treatment. Phase II trials have shown pemetrexed to have activity in
      patients with platinum resistant ovarian cancer. Several other thymidylate
      synthase inhibitors are in the early phase of development including BGC 945 and
      ZD-9331. Monoclonal antibodies that target the folate receptor have also shown
      potential in the development of ovarian cancer therapies. Farletuzumab is one of
      these antibodies. A recent phase III trial found that farletuzumab in combination
      with carboplatin and taxane did not meet the study's primary endpoint of
      progression-free survival (PFS). The post hoc exploratory analysis showed,
      however, a trend toward improved PFS in some patient subsets and further analysis
      is ongoing. The folate receptor is also utilized through folate conjugates.
      Vintafolide is one such agent which is currently in phase III development.
      Encouraging data from phase II trials showed an improvement in PFS from 2.7
      months to 5 months. Folate can also be conjugated to radioisotopes for both
      therapeutic and imaging purposes, and early studies have shown correlation with
      amount of disease to therapy response. CONCLUSION: Folate targeted agents
      continue to show promising antitumor activity in ovarian malignancy and initial
      clinical experience has demonstrated favorable toxicity profiles. Further
      development and resources targeted toward these therapies appear to be warranted.

PMID- 23863360
TI  - Morison's Pouch peritonectomy in cytoreductive surgery.

PMID- 23863361
TI  - Rapid analysis of 2-alkylcyclobutanones in irradiated meats, cheese and salmon by
      direct solvent extraction followed by GPC.
AB  - 2-Alkylcyclobutanones (2-ACBs) are recognized as a marker of irradiation in lipid
      containing food products. Here, a rapid method for the analysis of 2
      dodecylcyclobutanone (2-DCB) and 2-tetradecylcyclobutanone (2-TCB) in irradiated
      food products using direct solvent extraction (DSE) was developed, and the
      extraction efficiency was compared to that of the Soxhlet extraction method (EN
      1785), which is the official method for this analysis. Briefly, 2-ACBs were
      extracted either by using a Soxhlet apparatus or by DSE with n-hexane. The lipid
      extract was purified by GPC followed by a silica gel cartridge column. Finally, 2
      DCB and 2-TCB were measured using GC-MS/MS. The extraction efficiency of 2-ACBs
      by the DSE method was similar to that of the Soxhlet extraction method. The
      trueness of 2-DCB and 2-TCB spiked at 50 ng/g in lipid extracts of beef, pork,
      chicken, cheese and salmon with the proposed method were 76.6% to 91.6% and 81.3%
      to 109.0%, respectively. The limits of detection for 2-DCB and 2-TCB in lipid
      extracts were 15 and 20 ng/g, respectively. 

PMID- 23863362
TI  - Monitoring of radioactive substances in foods distributed in Kyoto, Japan (1991
      2011). - Comparison of detection rates and concentrations before and after the
      Fukushima Daiichi Nuclear Power Plant accident - .
AB  - Since the Chernobyl Nuclear Power Plant accident, radioactive substances have
      been continually monitored in foods collected in the city of Kyoto, Japan. The
      importance of the monitoring was increased by the Fukushima Daiichi Nuclear Power
      Plant accident in March 2011. Here, the detection rates and concentrations of
      radioactive substances were compared among food samples collected before and
      after the accident in Fukushima prefecture. Before the accident, (137)Cs was the
      only radioactive substance detected in foods. The detection rate was 70% for fish
      and shellfish samples and the highest concentration was 1.7 Bq/kg. It was also
      83% for fresh mushroom samples and the highest concentration was 7.5 Bq/kg. In
      contrast, the detection rate was low for vegetables and the concentrations were
      also lower than those of the above samples. On the other hand, after the
      accident, (131)I was detected in food produced in the Tohoku and Kanto areas.
      Actually, (131)I (3,400 Bq/kg), (134)Cs (280 Bq/kg), and (137)Cs (280 Bq/kg) were
      detected in mizuna, a leaf vegetable, on March 23, 2011. These radioactive
      substances were detected in all leaf vegetable samples examined in March and
      April 2011, but they were not detected in samples examined in November 2011.
      (131)I was not detected in any food sample examined after May 2011. However,
      (137)Cs (average=7.9 Bq/kg) was consistently detected in fish and shellfish
      samples until November, although the concentrations were less than the regulatory
      limits. It appears unlikely that foods containing radioactive substances over the
      regulatory limits are currently being distributed in Kyoto.

PMID- 23863363
TI  - [Structural analysis of subsidiary tar dyes contained in Food red No. 102].
AB  - Three unknown colors (A1, A2 and A3) in Food red No. 102 (R102) were identified
      by LC-MS and NMR analysis. Red dye A1 was azo rubine (AZO), which is not
      designated as a coloring agent in Japan. Red dye A2 was a structural isomer of
      Fast Red E (FRE), which is also not designated as a coloring agent in Japan. Red
      dye A3 was predicted to be an overreaction product of R102, possessing the R102
      structural framework. Furthermore, AZO, which was assumed to have been produced
      by dimerization of a diazonium salt used as a synthetic intermediate of R102, was
      also identified in Food red No. 2 (R2). 

PMID- 23863364
TI  - [Control of toxicity of Sarcocystis fayeri in horsemeat by freezing treatment and
      prevention of food poisoning caused by raw consumption of horsemeat].
AB  - More than 27 outbreaks per year of food poisoning caused by consuming horse meat
      were reported in Kumamoto Prefecture (including Kumamoto City) from January 2009
      to September 2011. It was found that the causative agent of the outbreaks was a
      protein with a molecular weight of 15 kDa that had originated from bradyzoites of
      Sarcocystis fayeri parasitizing the horse meat. Rabit ileal loop tests showed
      that pepsin treatment of homogenates of frozen horse meat containing the cysts of
      S. fayeri induced loss of toxicity, presumably by digestion of the proteinous
      causative agent(s). Slices of horse meat containing the cysts were frozen at
      below -20 degrees C for various periods. The cysts were collected after thawing
      the slices, then treated in an artificial stomach juice containing pepsin. The
      bradyzoites of the cysts kept at -20 degrees C for 48 hr or more completely
      disappeared. Simultaneously, the 15 kDa protein also disappeared in the frozen
      cysts. After notifying the public and recommending freezing treatment of horse
      meat, no subsequent cases of food poisoning were reported. This indicates that
      freezing of horse meat is effective to prevent the occurrence of food poisoning
      caused by consuming raw horse meat containing S. fayeri. 

PMID- 23863365
TI  - [Simultaneous determination of twelve sweeteners and nine preservatives in foods
      by solid-phase extraction and LC-MS/MS].
AB  - A rapid and simple method for the simultaneous determination of twelve sweeteners
      and nine preservatives in various foods by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) was developed. The sweeteners and preservatives were
      extracted from solid samples with 80% and 50% methanol and from liquid samples
      with 80% methanol, followed by Oasis WAX cartridge cleanup. The LC separation was
      performed on a XSelect CSH Phenyl-Hexyl column (5 MUm, 2.1 mm *150 mm) with a
      mobile phase of 10 mmol/L acetate buffer (pH 4.0)-acetonitrile and MS detection
      with negative ion electrospray ionization. The quantification limits of
      acesulfame K (AK), alitame (AL), aspartame (ASP), cyclamic acid (CYC), neotame
      (NEO), saccharin Na (SAC), p-hydroxybenzoic acid methyl (PHBA-Me), p
      hydroxybenzoic acid ethyl (PHBA-Et), p-hydroxybenzoic acid isopropyl (PHBA-iPr),
      p-hydroxybenzoic acid propyl (PHBA-Pr), p-hydroxybenzoic acid isobutyl (PHBA-iBu)
      and p-hydroxybenzoic acid butyl (PHBA-Bu) were 0.001 g/kg, those of dulcin (DU),
      glycyrrhizic acid (GLY), neohesperidin dihydrochalcone (NHDC), rebaudioside A
      (REB), stevioside (STV), sucralose (SUC) and benzoic acid (BA) were 0.005 g/kg,
      and those of sorbic acid (SOA) and dehydroacetic acid (DHA) were 0.02 g/kg. The
      mean recoveries from ten kinds of foods fortified at the levels of 0.02 and 0.2
      g/kg were 70.9-119.0%, and their relative standard deviations were 0.1-11.7%. 

PMID- 23863366
TI  - Survey of 7 trichothecenes in corn-derived feed and feed ingredients.
AB  - Corn is a major ingredient of mixed feed, and it has been reported that corn may
      be contaminated with deoxynivalenol (DON). There is also a possibility of
      contamination with other trichothecenes. Recently, corn-derived products such as
      Distiller's Dried Grains with Solubles (DDGS), corn gluten feed and corn gluten
      meal have been introduced and used for mixed feed. However the actual occurrence
      of trichothecenes has not been sufficiently investigated. So, in this study, we
      analyzed DON and 6 other trichothecenes, i.e., 3-acetyl-deoxynivalenol (3AcDON),
      15-acetyl-deoxynivalenol (15AcDON), T-2 toxin, HT-2 toxin, nivalenol, and
      fusarenon-X, in DDGS, corn gluten feed, corn gluten meal, and mixed feed
      containing corn-derived ingredients. The major trichothecenes identified in the
      samples tested were DON, 3AcDON and 15AcDON. In particular, DON, 3AcDON and
      15AcDON were detected in most DDGS and corn gluten feed samples. Most samples of
      mixed feed contained DON and 15AcDON, but only one mixed feed sample contained
      3AcDON. In contrast, corn gluten meal was contaminated with lower levels of these
      compounds than the other samples tested. Among 36 corn gluten meal samples, DON
      was detected in 24 and 15AcDON was detected in 20 samples. 3AcDON was not
      detected in any of the corn gluten meal samples. 

PMID- 23863367
TI  - Survival of Salmonella Enteritidis on four types of stainless steel surface under
      a dry condition and recovery by swabbing.
AB  - The survival and recovery of Salmonella Enteritidis inoculated on stainless steel
      surfaces with different metal contents and surface finishes were examined. Two S.
      Enteritidis strains possessing different levels of biofilm productivity were
      inoculated with tryptone soya broth (TSB) and egg yolk emulsion (EY) on the
      surface of stainless steel squares (1 cm * 1 cm) and stored at 22C under a dry
      condition. After storage, cells were recovered from the stainless steel surfaces
      by swabbing with a cotton swab. The numbers of cells recovered by swabbing and
      the cells remaining on the stainless steel squares were counted. The survival
      ratio of the strain possessing high biofilm productivity was greater than that of
      the strain possessing low biofilm productivity. The survival ratio of S.
      Enteritidis suspended in TSB was often higher than that in EY. There were no
      significant differences in the survival and recovery ratios of S. Enteritidis
      based on stainless steel composition or surface finish. From all except one
      sample, more than 98% of viable cells of S. Enteritidis were recovered by
      swabbing with a cotton swab.

PMID- 23863368
TI  - [Survey of pesticide residues in imported tea (1992.4-2010.3)].
AB  - A survey of pesticide residues in 116 imported tea samples on the Tokyo market
      from April 1992 to March 2010 was carried out. Twenty-two kinds of pesticides,
      including organophosphorus, organochlorine, pyrethroid and others, were detected
      at levels between trace (below 0.01 ppm) and 4.0 ppm in 76 samples. The rate of
      detection was 90% in non-fermented tea, 89% in semi-fermented tea, and 49% in
      fermented tea. Organophosphorus pesticide was not detected in puer tea, which is
      fermented with bacteria. The pesticide residues tended to be decreased by a
      fermentation process. However, organochlorine and pyrethroid pesticides appeared
      to be chemically stable, so they were still detected in fermented teas. Residue
      levels of these pesticides were calculated as less than 1% of ADI, except for
      ethion (45% of ADI) based on the daily intake of tea. Therefore, these teas
      should be safe when drunk in customary amounts. 

PMID- 23863369
TI  - Simultaneous identification of hydroxythiohomosildenafil, aminotadalafil,
      thiosildenafil, dimethylsildenafil, and thiodimethylsildenafil in dietary
      supplements using high-performance liquid chromatography-mass spectrometry.
AB  - We developed a method for the separation and identification of illegal
      adulterants (hydroxythiohomosildenafil, aminotadalafil, thiosildenafil,
      dimethylsildenafil, and thiodimethylsildenafil) from dietary supplements using
      high-performance liquid chromatography-mass spectrometry. The separation was
      achieved on a C18 column: the mobile phase consisted of 5 mM ammonium formate (pH
      6.3)-acetonitrile (75 : 25, v/v) and acetonitrile, with gradient elution at a
      flow rate of 0.2 mL/min. The proposed method could also be used to separate
      vardenafil, homosildenafil, and dimethylsildenafil, all of which have the same
      molecular weight. Furthermore, the proposed method could simultaneously separate
      hydroxythiohomosildenafil, aminotadalafil, thiosildenafil, dimethylsildenafil,
      thiodimethylsildenafil, vardenafil, and homosildenafil. Thus, this method may be
      useful to identify medicinal ingredients for erectile dysfunction and their
      analogs and to control the quality of dietary supplements. 

PMID- 23863370
TI  - [Validation study on a rapid multi-residue method for determination of pesticide
      residues in vegetables and fruits by LC-MS/MS].
AB  - A validation study was conducted on a rapid multiresidue method for determination
      of pesticide residues in vegetables and fruits by LC-MS/MS. Pesticide residues in
      the vegetables or fruits were extracted with acetonitrile in a disposable tube
      using a homogenizer, followed by salting out with anhydrous magnesium sulfate and
      sodium chloride in the presence of citrate salts for buffering. The extract was
      purified with a double-layered cartridge column (graphite carbon black/primary
      secondary amine silica gel; GCB/PSA). For citrus fruits a purification step with
      a C18 column was added (this column was connected to the GCB/PSA column). After
      removal of the solvent, the extract was resolved in methanol/water and analyzed
      by means of LC-MS/MS. The method was validated according to the method validation
      guideline of the Ministry of Health, Labour and Welfare of Japan; recovery tests
      were performed on 8 kinds of vegetables and fruits [cabbage, cucumber, Japanese
      radish, onion, potato, spinach, Amanatsumikan (a citrus fruit) and apple] by
      fortification of 161 pesticide residues at the concentrations 0.01 and 0.05 MUg/g
      (each concentration of pesticide residue was extracted from 2 samples on 5
      separate days). The trueness of the method for 127 pesticides in all 8
      commodities was 70-120% with satisfactory repeatability and within-run
      reproducibility. This method is concluded to be applicable for determination of
      pesticide residues in vegetables and fruits. 

PMID- 23863371
TI  - Energy efficiency for the removal of non-polar pollutants during ultraviolet
      irradiation, visible light photocatalysis and ozonation of a wastewater effluent.
AB  - This study aims to assess the removal of a set of non-polar pollutants in
      biologically treated wastewater using ozonation, ultraviolet (UV 254 nm low
      pressure mercury lamp) and visible light (Xe-arc lamp) irradiation as well as
      visible light photocatalysis using Ce-doped TiO2. The compounds tracked include
      UV filters, synthetic musks, herbicides, insecticides, antiseptics and
      polyaromatic hydrocarbons. Raw wastewater and treated samples were analyzed using
      stir-bar sorptive extraction coupled with comprehensive two-dimensional gas
      chromatography (SBSE-CG * GC-TOF-MS). Ozone treatment could remove most
      pollutants with a global efficiency of over 95% for 209 MUM ozone dosage. UV
      irradiation reduced the total concentration of the sixteen pollutants tested by
      an average of 63% with high removal of the sunscreen 2-ethylhexyl trans-4
      methoxycinnamate (EHMC), the synthetic musk 7-acetyl-1,1,3,4,4,6
      hexamethyltetrahydronaphthalene (tonalide, AHTN) and several herbicides. Visible
      light Ce-TiO2 photocatalysis reached ~70% overall removal with particularly high
      efficiency for synthetic musks. In terms of power usage efficiency expressed as
      nmol kJ(-1), the results showed that ozonation was by far the most efficient
      process, ten-fold over Xe/Ce-TiO2 visible light photocatalysis, the latter being
      in turn considerably more efficient than UV irradiation. In all cases the
      efficiency decreased along the treatments due to the lower reaction rate at lower
      pollutant concentration. The use of photocatalysis greatly improved the
      efficiency of visible light irradiation. The collector area per order decreased
      from 9.14 +/- 5.11 m(2) m(-3) order(-1) for visible light irradiation to 0.16 +/-
      0.03 m(2) m(-3) order(-1) for Ce-TiO2 photocatalysis. The toxicity of treated
      wastewater was assessed using the green alga Pseudokirchneriella subcapitata.
      Ozonation reduced the toxicity of treated wastewater, while UV irradiation and
      visible light photocatalysis limited by 20-25% the algal growth due to the
      accumulation of reaction by-products. Three transformation products were
      identified and tracked along the treatments.

PMID- 23863372
TI  - UV-induced effects on chlorination of creatinine.
AB  - Ultraviolet (UV) irradiation is commonly employed for water treatment in swimming
      pools to complement conventional chlorination, and to reduce the concentration of
      inorganic chloramine compounds. The approach of combining UV irradiation and
      chlorination has the potential to improve water quality, as defined by microbial
      composition. However, relatively little is known about the effects of this
      process on water chemistry. To address this issue, experiments were conducted to
      examine the effects of sequential UV254 irradiation/chlorination, as will occur
      in recirculating system of swimming pools, on disinfection byproduct (DBP)
      formation. Creatinine, which is present in human sweat and urine, was selected as
      the target precursor for these experiments. Enhanced formation of
      dichloromethylamine (CH3NCl2) and inorganic chloramines was observed to result
      from post-chlorination of UV-irradiated samples. Chlorocreatinine was found to be
      more sensitive to UV254 irradiation than creatinine; UV254 irradiation of
      chlorocreatinine resulted in opening of the ring structure, thereby yielding a
      series of intermediates that were more susceptible to free chlorine attack than
      their parent compound. The quantum yields for photodegradation of creatinine and
      chlorocreatinine at 254 nm were estimated at 0.011 +/- 0.002 mol/E and 0.144 +/-
      0.011 mol/E, respectively. The N-Cl bond was found to be common to UV-sensitive
      chlorinated compounds (e.g., inorganic chloramines, CH3NCl2, and
      chlorocreatinine); compounds that were less susceptible to UV-based attack
      generally lacked the N-Cl bond. This suggested that the N-Cl bond is susceptible
      to UV254 irradiation, and cleavage of the N-Cl bond appears to open or promote
      reaction pathways that involve free chlorine, thereby enhancing formation of some
      DBPs and promoting loss of free chlorine. Proposed reaction mechanisms to
      describe this behavior based on creatinine as a precursor are presented.

PMID- 23863373
TI  - Geographically distributed classification of surface water chemical parameters
      influencing fate and behavior of nanoparticles and colloid facilitated
      contaminant transport.
AB  - The current production and use of nanomaterials in consumer products have
      increased the concern about the possibility that these enter the rivers during
      their entire life cycle. Further, many aquatic contaminants undergo partitioning
      to the ubiquitous aquatic colloids. Here is presented the development of a set of
      European water types for environmental risk assessment of chemicals transported
      as nanovectors as is the case of environmental fate of manufactured nanoparticles
      and colloid-bound contaminants. A compilation of river quality geochemical data
      with information about multi-element composition for near 800 rivers in Europe
      was used to perform a principal component analysis (PCA) and define 6 contrasting
      water classes. With the aid of geographical information system algorithms, it was
      possible to analyse how the different sampling locations were predominantly
      represented within each European water framework directive drainage basin. These
      water classes and their associated Debye-Huckel parameter are determining factors
      to evaluate the large scale fate and behaviour of nanomaterials and other colloid
      transported pollutants in the European aquatic environment.

PMID- 23863374
TI  - Evaluations of the TiO2/simulated solar UV degradations of XAD fractions of
      natural organic matter from a bog lake using size-exclusion chromatography.
AB  - This work reports on the changes in compositions of humic acids (HAs) and fulvic
      acids (FAs) during photocatalytic degradation. The HAs and FAs were obtained from
      the XAD-resin fractionation of natural-organic matter (NOM) from a bog lake (Lake
      Hohloh, Black Forest, Germany). Degussa P-25 titanium dioxide (TiO2) in a
      suspension and a solar UV simulator (batch reactor) were used in the experiments.
      The photocatalytic degradation of the HAs and FAs were monitored using size
      exclusion chromatography (SEC) equipped with dissolved organic carbon (DOC) and
      ultraviolet (UV254) detection (SEC-DOC and SEC-UV254) and UV-Vis
      spectrophotometry. The evolutions of the photocatalytic degradations of the HA
      and FA fractions were selective. The photocatalytic degradation started with the
      degradations of high molecular weight compounds with relatively high UV254
      absorbances in the HA and FA fractions to yield low molecular weight compounds
      showing less specific UV254 absorbances. Observance of the same tendency for the
      original NOM from Lake Hohloh indicates that these XAD-fractions still having
      complex compound mixtures. However, the larger molecular weight fractions of the
      FAs showed higher preferential adsorptions onto TiO2, which caused their faster
      degradation rates. Furthermore, FAs showed a greater reduction of the total THM
      formation potential (TTHMFP) and the organic halogen compounds adsorbable on
      activated carbon formation potential (AOXFP), in comparison with the HAs.

PMID- 23863375
TI  - Coupling membrane separation and photocatalytic oxidation processes for the
      degradation of pharmaceutical pollutants.
AB  - The coupling of membrane separation and photocatalytic oxidation has been studied
      for the removal of pharmaceutical pollutants. The retention properties of two
      different membranes (nanofiltration and reverse osmosis) were assessed.
      Comparable selectivity on the separation of pharmaceuticals were observed for
      both membranes, obtaining a permeate stream with concentrations of each
      pharmaceutical below 0.5 mg L(-)(1) and a rejected flux highly concentrated (in
      the range of 16-25 mg L(-)(1) and 18-32 mg L(-)(1) of each pharmaceutical for NF
      90 and BW-30 membranes, respectively), when an initial stream of six
      pharmaceuticals was feeding to the membrane system (10 mg L(-)(1) of each
      pharmaceutical). The abatement of concentrated pharmaceuticals of the rejected
      stream was evaluated by means of heterogeneous photocatalytic oxidation using
      TiO2 and Fe2O3/SBA-15 in presence of hydrogen peroxide as photo-Fenton system.
      Both photocatalytic treatments showed remarkable removals of pharmaceutical
      compounds, achieving values between 80 and 100%. The nicotine was the most
      refractory pollutant of all the studied pharmaceuticals. Photo-Fenton treatment
      seems to be more effective than TiO2 photocatalysis, as high mineralization
      degree and increased nicotine removal were attested. This work can be considered
      an interesting approach of coupling membrane separation and heterogeneous
      photocatalytic technologies for the successful abatement of pharmaceutical
      compounds in effluents of wastewater treatment plants.

PMID- 23863377
TI  - Discharge-based QMRA for estimation of public health risks from exposure to
      stormwater-borne pathogens in recreational waters in the United States.
AB  - This study is the first to report a quantitative microbial risk assessment (QMRA)
      on pathogens detected in stormwater discharges-of-concern, rather than relying on
      pathogen measurements in receiving waters. The pathogen concentrations include
      seven "Reference Pathogens" identified by the U.S. EPA: Cryptosporidium, Giardia,
      Salmonella, Norovirus, Rotavirus, Enterovirus, and Adenovirus. Data were
      collected from 12 sites representative of seven discharge types (including
      residential, commercial/industrial runoff, agricultural runoff, combined sewer
      overflows, and forested land), mainly during wet weather conditions during which
      times human health risks can be substantially elevated. The risks calculated
      herein therefore generally apply to short-term conditions (during and just after
      rainfall events) and so the results can be used by water managers to potentially
      inform the public, even for waters that comply with current criteria (based as
      they are on a 30-day mean risk). Using an example waterbody and mixed source,
      pathogen concentrations were used in QMRA models to generate risk profiles for
      primary and secondary water contact (or inhalation) by adults and children. A
      number of critical assumptions and considerations around the QMRA analysis are
      highlighted, particularly the harmonization of the pathogen concentrations
      measured in discharges during this project with those measured (using different
      methods) during the published dose-response clinical trials. Norovirus was the
      most dominant predicted health risk, though further research on its dose-response
      for illness (cf. infection) is needed. Even if the example mixed-source
      concentrations of pathogens had been reduced 30 times (by inactivation and
      mixing), the predicted swimming-associated illness rates - largely driven by
      Norovirus infections - can still be appreciable. Rotavirus generally induced the
      second-highest incidence of risk among the tested pathogens while risks for the
      other Reference Pathogens (Giardia, Cryptosporidium, Adenovirus, Enterovirus and
      Salmonella) were considerably lower. Secondary contact or inhalation resulted in
      considerable reductions in risk compared to primary contact. Measurements of
      Norovirus and careful incorporation of its concentrations into risk models
      (harmonization) should be a critical consideration for future QMRA efforts. The
      discharge-based QMRA approach presented herein is particularly relevant to cases
      where pathogens cannot be reliably detected in receiving waters with detection
      limits relevant to human health effects.

PMID- 23863376
TI  - Identifying the sources and fate of anthropogenically impacted dissolved organic
      matter (DOM) in urbanized rivers.
AB  - Anthropogenic activities have dramatically changed the loads and compositions of
      dissolved organic matter (DOM) in urbanized streams. In this study, the spatial
      and temporal variations of DOM in the anthropogenically impacted Zhujiang River
      were investigated by analyzing the water samples in an upstream, urbanized area
      and downstream of the rivers on different days of one year. The results indicated
      that the levels of dissolved organic carbon (DOC) and total phosphorus (TP) were
      unaffected by seasonal changes, but the specific UV254 absorbance (SUVA) values
      and the total nitrogen (TN) content were greater in the winter than those in the
      summer. Parallel factor (PARAFAC) analysis of the excitation emission matrices
      (EEM) revealed the presence of three anthropogenically derived components
      [tryptophan-like (C1) and tyrosine-like proteins (C3) and anthropogenic humic
      substances (C5)] in the urbanized rivers, and they had greater seasonal and
      spatial variability than the terrestrial and microbial humic substances (C2 and
      C4). Cluster analysis revealed that treated wastewater was an important source of
      DOM in the urbanized streams. Photodegradation experiments indicated that the DOM
      in the populous area of the rivers had greater photodegradation potentials than
      that in the downstream region or in the natural waters. Interestingly, that the
      anthropogenic humic substances (C5) were considerably more photoreactive than the
      other four PARAFAC components, which exhibited a decrease of 80% after exposure
      to sunlight for 0.5 d. This study suggests that the treated wastewater could be
      an important input to the DOM in the urbanized rivers and the naturally occurring
      photodegradation could help in eliminating the anthropogenic DOM during their
      transport.

PMID- 23863378
TI  - Toxicity characterization of urban stormwater with bioanalytical tools.
AB  - Stormwater harvesting has become an attractive alternative strategy to address
      the rising demand for urban water supply due to limited water sources and
      population growth. Nevertheless, urban stormwater is also a major source of
      surface water pollution. Runoff from different urban catchments with source
      contributions from anthropogenic activities and various land uses causes variable
      contaminant profiles, thus posing a challenging task for environmental monitoring
      and risk assessment. A thorough understanding of raw stormwater quality is
      essential to develop appropriate treatment facilities for potential indirect
      potable reuse of stormwater. While some of the key chemical components have
      previously been characterized, only scarce data are available on stormwater
      toxicity. We benchmarked stormwater samples from urban, residential and
      industrial sites across various Australian capital cities against samples from
      the entire water cycle, from sewage to drinking water. Six biological endpoints,
      targeting groups of chemicals with modes of toxic action of particular relevance
      for human and environmental health, were investigated: non-specific toxicity
      (Microtox and combined algae test), the specific modes of action of phytotoxicity
      (combined algae test), dioxin-like activity (AhR-CAFLUX), and estrogenicity (E
      SCREEN), as well as reactive toxicity encompassing genotoxicity (umuC) and
      oxidative stress (AREc32). Non-specific toxicity was highly variable across
      sites. The baseline toxicity equivalent concentrations of the most polluted
      samples were similar to secondary treated effluent from wastewater treatment
      plants. Phytotoxicity results correlated well with the measured herbicide
      concentrations at all sites. High estrogenicity was found in two sampling events
      and could be related to sewage overflow. Genotoxicity, dioxin-like activity, and
      oxidative stress response were evident in only three of the samples where the
      stormwater drain was beside a heavy traffic road, confirming that road runoff is
      the potential source of contaminants, while the bioanalytical equivalent
      concentrations (BEQ) of these samples were similar to those of raw sewage. This
      study demonstrates the benefit of bioanalytical tools for screening-level
      stormwater quality assessment, forming the basis for the evaluation of future
      stormwater treatment and reuse schemes. 

PMID- 23863379
TI  - Long-term impact of anaerobic reaction time on the performance and granular
      characteristics of granular denitrifying biological phosphorus removal systems.
AB  - Removal of nitrogen and phosphorus (P) from wastewater is successfully and widely
      practiced in systems employing both granular sludge technology and enhanced
      biological P removal (EBPR) processes; however, the key parameter, anaerobic
      reaction time (AnRT), has not been thoroughly investigated. Successful EBPR is
      highly dependent on an appropriate AnRT, which induces carbon and polyphosphate
      metabolism by phosphorus accumulating organisms (PAOs). Therefore, the long-term
      impact of AnRT on denitrifying P removal performance and granular characteristics
      was investigated in three identical granular sludge sequencing batch reactors
      with AnRTs of 90 (R1), 120 (R2) and 150 min (R3). The microbial community
      structures and anaerobic stoichiometric parameters related to various AnRTs were
      monitored over time. Free nitrite acid (FNA) accumulation (e.g., 0.0008-0.0016 mg
      HNO2-N/L) occurred frequently owing to incomplete denitrification in the
      adaptation period, especially in R3, which influenced the anaerobic/anoxic
      intracellular intermediate metabolites and activities of intracellular enzymes
      negatively, resulting in lower levels of poly-P and reduced activity of
      polyphosphate kinase. As a result, the Accumulibacter-PAOs population decreased
      from 51 +/- 2.5% to 43 +/- 2.1% when AnRT was extended from 90 to 150 min,
      leading to decreased denitrifying P removal performance. Additionally, frequent
      exposure of microorganisms to the FNA accumulation and anaerobic endogenous
      conditions in excess AnRT cases (e.g., 150 min) stimulated increased
      extracellular polymeric substances (EPS) production by microorganisms, resulting
      in enhanced granular formation and larger granules (size of 0.6-1.2 mm), but
      decreasing anaerobic PHA synthesis and glycogen hydrolysis. Phosphorus removal
      capacity was mediated to some extent by EPS adsorption in granular sludge systems
      that possessed more EPS, longer AnRT and relatively higher GAOs.

PMID- 23863380
TI  - The impact of the hydroxyl radical photochemical sources on the rivastigmine drug
      transformation in mimic and natural waters.
AB  - In this paper we investigated the degradation of the rivastigmine drug induced by
      hydroxyl radical in synthetic and natural waters focusing on both reactivity and
      photoproducts identification. The hydroxyl radical formation rate was quantified
      by using terephthalic acid as trapping molecule and it was related with the
      rivastigmine degradation rate. The second order rate constant between hydroxyl
      radical and rivastigmine was estimated to be ~ 5.8 * 10(9) M(-1) s(-1).
      Irradiation of rivastigmine in three natural waters (rain, lake and river) and
      comparison with degradation rates observed in synthetic solutions using nitrite,
      nitrate and hydrogen peroxide suggest that, in addition to hydroxyl radical, also
      nitroderived radicals (NO/NO2) are responsible for the pollutant degradation in
      natural media. In fact, the evaluated degradation rates in three natural waters
      are greatly higher than those estimated considering only the reactivity with
      photogenerated hydroxyl radical. Using nitrites and nitrates as photochemical OH
      source, the rivastigmine degradation cannot be described considering only the
      hydroxyl radical reactivity suggesting that NO and NO2 radicals could play a key
      role during indirect degradation. Moreover main degradation products have been
      identified by means of HPLC-MS. Hydroxylation of the aromatic ring as well as
      carbamate and amino chain oxidation were suggested as main reaction mechanisms,
      but also nitroderived compounds were characterized. Finally polychromatic
      irradiations of three rivastigmine doped natural waters (rain, river and lake)
      underlined the role of the indirect degradation that needs to be considered when
      direct degradation of selected pollutants is negligible under environmental-like
      conditions.

PMID- 23863382
TI  - Impact on reactor configuration on the performance of anaerobic MBRs: treatment
      of settled sewage in temperate climates.
AB  - The treatment efficiency and membrane performance of a granular and suspended
      growth anaerobic membrane bioreactor (G-AnMBR and AnMBR respectively) were
      compared and evaluated. Both anaerobic MBRs were operated in parallel during 250
      days with low strength wastewater and under UK weather conditions. Both systems
      presented COD and BOD removal efficiencies of 80-95% and >90% respectively.
      Effluent BOD remained between 5 and 15 mgBOD L(-1) through the experimental
      period while effluent COD increased from 25 mg L(-1) to 75 mg L(-1) as
      temperature decreased from 25  degrees C to 10  degrees C respectively indicating
      the production of non biodegradable organics at lower temperatures. Although
      similar levels of low molecular weight organics were present in the sludge
      supernatant, recycling of the mixed liquor from the membrane tank to the
      bioreactor at a low upflow velocity enhanced interception of solids in the sludge
      bed of the G-AnMBR limiting the solid and colloidal load to the membrane as
      compared to the suspended system. Results from flux step test showed that
      critical flux increased from 4 to 13 L m(-2) h(-1) and from 3 to 5 L m(-2) h(-1)
      with gas sparging intensities varying from 0.007 m s(-1) to 0.041. Additional
      long term trials in which the effect of gas sparging rate and backwashing
      efficiency were assessed confirmed the lower fouling propensity of the G-AnMBR.

PMID- 23863381
TI  - Molecular assessment of the sensitivity of sulfate-reducing microbial communities
      remediating mine drainage to aerobic stress.
AB  - Sulfate-reducing permeable reactive zones (SR-PRZs) are microbially-driven
      anaerobic systems designed for the removal of heavy metals and sulfate in mine
      drainage. Environmental perturbations, such as oxygen exposure, may adversely
      affect system stability and long-term performance. The objective of this study
      was to examine the effect of two successive aerobic stress events on the
      performance and microbial community composition of duplicate laboratory-scale
      lignocellulosic SR-PRZs operated using the following microbial community
      management strategies: biostimulation with ethanol or carboxymethylcellulose;
      bioaugmentation with sulfate-reducing or cellulose-degrading enrichments;
      inoculation with dairy manure only; and no inoculation. A functional gene-based
      approach employing terminal restriction fragment length polymorphism and
      quantitative polymerase chain reaction targeting genes of sulfate-reducing
      (dsrA), cellulose-degrading (cel5, cel48), fermentative (hydA), and methanogenic
      (mcrA) microbes was applied. In terms of performance (i.e., sulfate removal),
      biostimulation with ethanol was the only strategy that clearly had an effect
      (positive) following exposure to oxygen. In terms of microbial community
      composition, significant shifts were observed over the course of the experiment.
      Results suggest that exposure to oxygen more strongly influenced microbial
      community shifts than the different microbial community management strategies.
      Sensitivity to oxygen exposure varied among different populations and was
      particularly pronounced for fermentative bacteria. Although the community
      structure remained altered after exposure, system performance recovered,
      indicating that SR-PRZ microbial communities were functionally redundant. Results
      suggest that pre-exposure to oxygen might be a more effective strategy to improve
      the resilience of SR-PRZ microbial communities relative to bioaugmentation or
      biostimulation.

PMID- 23863384
TI  - Large Eddy Simulation of complex sidearms subject to solar radiation and surface
      cooling.
AB  - Large Eddy Simulation (LES) is used to model two lake sidearms subject to heating
      from solar radiation and cooling from a surface flux. The sidearms are part of
      Lake Audrey, NJ, USA and Lake Alexandrina, SA, Australia. The simulation domains
      are created using bathymetry data and the boundary is modelled with an Immersed
      Boundary Method. We investigate the cooling and heating phases with separate
      quasi-steady state simulations. Differential heating occurs in the cavity due to
      the changing depth. The resulting temperature gradients drive lateral flows.
      These flows are the dominant transport process in the absence of wind. Study in
      this area is important in water quality management as the lateral circulation can
      carry particles and various pollutants, transporting them to and mixing them with
      the main lake body. 

PMID- 23863383
TI  - Photochemistry of excited-state species in natural waters: a role for particulate
      organic matter.
AB  - Laser flash photolysis (LFP) was used to characterize a triplet excited state
      species isolated from Black River and San Joaquin wetlands particulate organic
      matter (POM). The solubilized organic matter, isolated from POM by pH-independent
      diffusion in distilled water, was named PdOM. UV-visible absorption spectroscopy,
      excitation-emission matrix spectroscopy (EEMs), and (1)H NMR were used to
      characterize the PdOM. While LFP of dissolved organic matter (DOM) is known to
      generate the solvated electron, LFP of the PdOM transient in argon-, air-, and
      nitrous oxide-saturated solutions indicated that this was a triplet excited state
      species ((3)PdOM*). The lifetime and the reactivity of (3)PdOM* with sorbic acid,
      a triplet state quencher, were compared with that of the triplet excited state of
      benzophenone, a DOM proxy. A second excited state species (designated DOM*), with
      a longer lifetime, was reported in a number of previous studies but not
      characterized. The lifetime of DOM*, measured for seventeen organic matter
      isolates, lignin, tannic acid, and three wetlands plant extracts, was shown to
      differentiate allochthonous from autochthonous DOM. (3)POM* and DOM* were also
      observed in lake water and a constructed wetlands' water. Aqueous extracts of
      fresh and aged plant material from the same wetland were shown to be one source
      of these excited state species. This study provides evidence of a role for POM in
      the photochemistry of natural and constructed wetland waters.

PMID- 23863385
TI  - Comment on "A new insight into membrane fouling mechanism in submerged membrane
      bioreactor: osmotic pressure during cake layer filtration" by Zhang et al. [Water
      Research 47 (2013) 2777-2786].

PMID- 23863386
TI  - Identification of antimicrobial resistant bacteria in rivers: insights into the
      cultivation bias.
AB  - In the present study, the antimicrobial resistant (AR) bacteria were quantified
      and identified in different river samples using in parallel a culture-based
      approach and a culture-independent one. The objective was to evaluate the
      importance of the cultivation bias when studying antimicrobial resistance among
      environmental bacteria. Three different river samples covering a gradient of
      anthropic influence were tested and three different antimicrobial compounds were
      used as selective agents: amoxicillin, tetracycline and sulfamethoxazole. From a
      quantitative point of view, our results highlight the importance of the culture
      media used, as for the same sample and the same selective agent significant
      differences were observed in the counts of culturable AR bacteria depending on
      the culture media used. The identification of AR bacteria through culture or
      culture-independent methods put on evidence AR bacterial communities that differ
      dramatically: gamma-proteobacteria and more specifically Aeromonadaceae dominated
      among the isolates while beta-proteobacteria (Comamonadaceae), dominated among
      the sequences obtained without culture. Altogether these results highlight the
      necessity to develop a methodological consensus preferably without culture, to
      approach this important topic in the coming years. 

PMID- 23863387
TI  - Role of molecular structure on bioelectrochemical reduction of mononitrophenols
      from wastewater.
AB  - The effect of nitro-substituent on mononitrophenol (o-nitrophenol (ONP), m
      nitrophenol (MNP) and p-nitrophenol (PNP)) reduction in a bioelectrochemical
      system (BES) was investigated in this study. The results show that the removal of
      all three nitrophenols was significantly enhanced with more negative cathode
      potential and shortened hydraulic retention time in the BESs. Moreover, the
      reduction of the three nitrophenols followed in the order of ONP > MNP > PNP in
      the BESs. Both quantum chemical calculation using density function theory and
      cyclic voltammetry analysis confirmed the reductive sequence of the three
      nitrophenols. In addition, the acute toxicity of nitrophenol effluent
      significantly decreased while its biodegradability was enhanced after treatment
      in the BES. Therefore, the BES technology offers bright prospects for efficient
      treatment of nitrophenol-containing wastewater.

PMID- 23863388
TI  - Aerobic biotransformation potential of a commercial mixture of naphthenic acids.
AB  - The biotransformation potential of a commercial naphthenic acid (NA) mixture (NA
      sodium salt; TCI Chemicals) under aerobic conditions was investigated using mixed
      aerobic cultures developed under various levels and duration of NA exposure. A
      culture enriched using the commercial NA mixture as the sole carbon source
      degraded NAs in a range of NA concentrations, regardless of culture age and the
      presence of a co-substrate; however, only 28.5% of the NA-carbon was detected as
      CO2 while 44% was utilized for biomass growth. A fraction of the NA mixture (15
      26%) was persistent under all conditions studied. In contrast, a culture fed with
      a degradable synthetic wastewater only (NA un-amended culture) and another
      culture fed with the same wastewater and 50 mg NA/L (NA-amended culture), over
      time lost their ability to degrade NAs. Analysis of the 16S rRNA gene based clone
      library revealed that 80% of the NA-enriched culture belonged to the gamma
      Proteobacteria class and was largely dominated by phylotypes most closely related
      to known NA and hydrocarbon degraders such as Pseudomonas and Microbulbifer. The
      results of this study indicate that although significant NA degradation is
      possible, only a small fraction of the NA mixture is completely mineralized to
      CO2. Further investigation into the biotransformation products and conditions
      affecting NA biodegradation under realistic refinery and environmental conditions
      will help to design effective treatment and bioremediation processes.

PMID- 23863389
TI  - Phosphate recovery from wastewater using engineered superparamagnetic particles
      modified with layered double hydroxide ion exchangers.
AB  - An innovative nanocomposite material is proposed for phosphate recovery from
      wastewater using magnetic assistance. Superparamagnetic microparticles modified
      with layered double hydroxide (LDH) ion exchangers of various compositions act as
      phosphate adsorbers. Magnetic separation and chemical regeneration of the
      particles allows their reuse, leading to the successful recovery of phosphate.
      Based upon the preliminary screening of different LDH ion exchanger modifications
      for phosphate selectivity and uptake capacity, MgFe-Zr LDH coated magnetic
      particles were chosen for further characterization and application. The
      adsorption kinetics of phosphate from municipal wastewater was studied in
      dependence with particle concentration, contact time and pH. Adsorption isotherms
      were then determined for the selected particle system. Recovery of phosphate and
      regeneration of the particles was examined via testing a variety of desorption
      solutions. Reusability of the particles was demonstrated for 15
      adsorption/desorption cycles. Adsorption in the range of 75-97% was achieved in
      each cycle after 1 h contact time. Phosphate recovery and enrichment was possible
      through repetitive application of the desorption solution. Finally, a pilot scale
      experiment was carried out by treating 125 L of wastewater with the particles in
      five subsequent 25 L batches. Solid-liquid separation on this scale was carried
      out with a high-gradient magnetic filter (HGMF).

PMID- 23863390
TI  - Do biological-based strategies hold promise to biofouling control in MBRs?
AB  - Biofouling in membrane bioreactors (MBRs) remains a primary challenge for their
      wider application, despite the growing acceptance of MBRs worldwide. Research
      studies on membrane fouling are extensive in the literature, with more than 200
      publications on MBR fouling in the last 3 years; yet, improvements in practice on
      biofouling control and management have been remarkably slow. Commonly applied
      cleaning methods are only partially effective and membrane replacement often
      becomes frequent. The reason for the slow advancement in successful control of
      biofouling is largely attributed to the complex interactions of involved
      biological compounds and the lack of representative-for-practice experimental
      approaches to evaluate potential effective control strategies. Biofouling is
      driven by microorganisms and their associated extra-cellular polymeric substances
      (EPS) and microbial products. Microorganisms and their products convene together
      to form matrices that are commonly treated as a black box in conventional control
      approaches. Biological-based antifouling strategies seem to be a promising
      constituent of an effective integrated control approach since they target the
      essence of biofouling problems. However, biological-based strategies are in their
      developmental phase and several questions should be addressed to set a roadmap
      for translating existing and new information into sustainable and effective
      control techniques. This paper investigates membrane biofouling in MBRs from the
      microbiological perspective to evaluate the potential of biological-based
      strategies in offering viable control alternatives. Limitations of available
      control methods highlight the importance of an integrated anti-fouling approach
      including biological strategies. Successful development of these strategies
      requires detailed characterization of microorganisms and EPS through the proper
      selection of analytical tools and assembly of results. Existing
      microbiological/EPS studies reveal a number of implications as well as knowledge
      gaps, warranting future targeted research. Systematic and representative
      microbiological studies, complementary utilization of molecular and biofilm
      characterization tools, standardized experimental methods and validation of
      successful biological-based antifouling strategies for MBR applications are
      needed. Specifically, in addition, linking these studies to relevant operational
      conditions in MBRs is an essential step to ultimately develop a better
      understanding and more effective and directed control strategy for biofouling. 

PMID- 23863391
TI  - Assessing the effects of sodium hypochlorite exposure on the characteristics of
      PVDF based membranes.
AB  - Sodium hypochlorite is commonly used as a cleaning agent to remove adsorbed
      foulants from PVDF based micro/ultra filtration membranes in water and wastewater
      treatment applications. Although effective for fouling control, extended sodium
      hypochlorite exposure can affect the physical/chemical characteristics and hinder
      the treatment performance of these membranes. To assess these effects, PVDF based
      membranes were exposed to sodium hypochlorite at different concentrations for
      varying periods of time, and the physical/chemical characteristics of the virgin
      and sodium hypochlorite exposed membranes were compared. The membranes were
      characterized based on chemical composition (FTIR and NMR), mechanical strength
      (yield strength), surface hydrophilicity (contact angle), pore size and porosity
      (scanning electron microscopy and challenge test), and membrane resistance (clean
      water permeation test). The results indicated that exposure dose and
      concentration of the sodium hypochlorite used have significant influence on the
      membrane characteristics. The impact of sodium hypochlorite exposure on the
      parameters investigated could be most accurately and consistently correlated to
      an exposure dose relationship of the form C(n)t (where, C = concentration and t =
      exposure time) rather than the Ct relationship commonly used to define the extent
      of exposure to cleaning agents. For all the parameters investigated, the power
      coefficient n was less than 1 indicating that time had a greater impact on the
      changes than did the concentration of the sodium hypochlorite. The results
      suggest that the use of sodium hypochlorite for chemical cleaning, at
      concentrations that are higher than those typically used for chemical cleaning
      would have less of an effect on the characteristics of the membrane materials.
      Changes in the characteristics were attributed to the oxidation of the
      hydrophilic additives (HA) present in blended PVDF membranes.

PMID- 23863392
TI  - Differences in microcystin production and genotype composition among Microcystis
      colonies of different sizes in Lake Taihu.
AB  - The cyanobacterium Microcystis, which occurs as colonies of different sizes under
      natural conditions, can produce toxic microcystins (MCs). To monitor the toxicity
      and assess the risk of Microcystis blooms in Lake Taihu, it is important to
      investigate the relationship between MC production and Microcystis colony size.
      In this study, we classified Microcystis collected from Zhushan Bay of Lake Taihu
      during blooms into four classes with size of <50 MUm, 50-100 MUm, 100-270 MUm and
      >270 MUm and studied their differences in MC production and genetic structure.
      The results showed that colonies with size of <50, 50-100, 100-270 and >270 MUm
      produced 12.2 +/- 11.2%, 19.5 +/- 7.9%, 61.3 +/- 12.6%, and 7.0 +/- 9.6% of total
      MC, respectively. The proportion of cell density of colonies with size of 50-100,
      100-270 and >270 MUm was positively correlated with MC concentration during
      blooms, while that of colonies with size of <50 MUm was negatively correlated.
      The MC cell quota tended to be higher during blooms in colonies with larger size
      except that of colonies with size of 100-270 MUm was higher than that of colonies
      with size of >270 MUm from June 11 to September 16. Colonies with size of <50 MUm
      showed the highest proportion of the less toxic MC congener MC-RR, and colonies
      with size of >100 MUm showed higher proportion of the most toxic MC congener MC
      LR than colonies with size of <100 MUm. Real-time PCR indicated that larger
      colonies had higher proportion of potential toxic genotype. Principal component
      analysis of PCR-denaturing gradient gel electrophoresis profile showed that cpcBA
      and mcyJ genotype compositions were different between colonies with size of <50
      MUm and colonies with size of >50 MUm, and cpcBA genotype composition was also
      different among colonies with size of 50-100 MUm, 100-270 MUm and >270 MUm. These
      results indicated that MC cell quota and congener composition were different in
      Microcystis colonies with different sizes in Lake Taihu during blooms, and the
      differences in MC production in colonies with different size resulted chiefly
      from the difference in their genotype composition. Therefore, the authorities of
      water quality monitoring and drinking water supply service in Lake Taihu should
      be alert that the toxicity of Microcystis colony with different size was
      different during blooms, and the high abundance of colonies larger than 50 MUm
      could be an indicator of relatively high bloom toxicity.

PMID- 23863393
TI  - Aminopolycarboxylic acid functionalized adsorbents for heavy metals removal from
      water.
AB  - Due to the excellent chelating properties of aminopolycarboxylic acid (APCAs),
      they can be used for the removal of metals from contaminated waters. This paper
      reviews the research results obtained for both commercial and self-prepared
      adsorbents functionalized with four most common APCAs: iminodiacetic acid (IDA),
      nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), and
      diethylenetriaminepentaacetic acid (DTPA). The structural characteristics and
      unique metal binding properties of these chelating adsorbents are presented. The
      theory of the adsorption phenomena is discussed based on the kinetics of
      adsorption, equilibrium adsorption isotherm models, and thermodynamic models. The
      most important applications of APCA-functionalized adsorbents are also described.
      APCA-functionalized adsorbents are found to be highly promising materials for
      metal removal from contaminated waters. 

PMID- 23863394
TI  - Fossil organic carbon in wastewater and its fate in treatment plants.
AB  - This study reports the presence of fossil organic carbon in wastewater and its
      fate in wastewater treatment plants. The findings pinpoint the inaccuracy of
      current greenhouse gas accounting guidelines which defines all organic carbon in
      wastewater to be of biogenic origin. Stable and radiocarbon isotopes ((13)C and
      (14)C) were measured throughout the process train in four municipal wastewater
      treatment plants equipped with secondary activated sludge treatment. Isotopic
      mass balance analyses indicate that 4-14% of influent total organic carbon (TOC)
      is of fossil origin with concentrations between 6 and 35 mg/L; 88-98% of this is
      removed from the wastewater. The TOC mass balance analysis suggests that 39-65%
      of the fossil organic carbon from the influent is incorporated into the activated
      sludge through adsorption or from cell assimilation while 29-50% is likely
      transformed to carbon dioxide (CO2) during secondary treatment. The fossil
      organic carbon fraction in the sludge undergoes further biodegradation during
      anaerobic digestion with a 12% decrease in mass. 1.4-6.3% of the influent TOC
      consists of both biogenic and fossil carbon is estimated to be emitted as fossil
      CO2 from activated sludge treatment alone. The results suggest that current
      greenhouse gas accounting guidelines, which assume that all CO2 emission from
      wastewater is biogenic may lead to underestimation of emissions.

PMID- 23863395
TI  - Effects of chloride, sulfate and natural organic matter (NOM) on the accumulation
      and release of trace-level inorganic contaminants from corroding iron.
AB  - This study examined effects of varying levels of anions (chloride and sulfate)
      and natural organic matter (NOM) on iron release from and accumulation of
      inorganic contaminants in corrosion scales formed on iron coupons exposed to
      drinking water. Changes of concentrations of sulfate and chloride were observed
      to affect iron release and, in lesser extent, the retention of representative
      inorganic contaminants (vanadium, chromium, nickel, copper, zinc, arsenic,
      cadmium, lead and uranium); but, effects of NOM were more pronounced. DOC
      concentration of 1 mg/L caused iron release to increase, with average soluble and
      total iron concentrations being four and two times, respectively, higher than
      those in the absence of NOM. In the presence of NOM, the retention of inorganic
      contaminants by corrosion scales was reduced. This was especially prominent for
      lead, vanadium, chromium and copper whose retention by the scales decreased from
      >80% in the absence of NOM to <30% in its presence. Some of the contaminants,
      notably copper, chromium, zinc and nickel retained on the surface of iron coupons
      in the presence of DOC largely retained their mobility and were released readily
      when ambient water chemistry changed. Vanadium, arsenic, cadmium, lead and
      uranium retained by the scales were largely unsusceptible to changes of NOM and
      chloride levels. Modeling indicated that the observed effects were associated
      with the formation of metal-NOM complexes and effects of NOM on the sorption of
      the inorganic contaminants on solid phases that are typical for iron corrosion in
      drinking water.

PMID- 23863396
TI  - Emerging pesticide metabolites in groundwater and surface water as determined by
      the application of a multimethod for 150 pesticide metabolites.
AB  - A recently developed multimethod for the determination of 150 pesticide
      metabolites was exemplarily applied to 58 samples of groundwater and surface
      water. 37 of these metabolites were detected in at least two samples with a
      concentration >=0.025 MUg/L. The detected metabolites were ranked according to
      their concentration and frequency of detection. Findings are clearly dominated by
      metabolites of chloroacetanilide herbicides, but metabolites of sulfonylurea and
      thiocarbamate herbicides and other herbicides (dichlobenil) together with
      metabolites of some fungicides (tolylfluanid, chlorothalonil, trifloxystrobin)
      were also prominent. A number of 17 of the ranked metabolites are denoted as
      emerging metabolites because no reports on their previous detection in
      groundwater or surface water were found. Most of them, however, were correctly
      predicted to occur in the summary reports of the European pesticide approval
      process. Median total concentrations of the analysed pesticide metabolites summed
      up to 0.62 MUg/L in groundwater and 0.33 MUg/L in surface waters. While the
      concentration of the individual metabolites is usually low (<0.1 MUg/L) the
      diversity of metabolites found in one sample can be large; between two and six
      metabolites were detected most frequently (maximum of 12 metabolites). Runoff
      from urban surfaces was investigated in this study and also here previously
      undetected pesticide (biocide) metabolites were detected. The emerging pesticide
      metabolites detected in environmental water samples in this study require more
      extended monitoring.

PMID- 23863397
TI  - Adult-type bimalleolar ankle fracture in children: report of two cases.
AB  - Ankle fractures patterns in children may vary depending on the maturity of the
      distal tibial and fibular physis. Bimalleolar ankle fracture is an exceedingly
      rare fracture pattern in children and has been reported once in the current
      English literature. Two further adolescents with bimalleolar ankle fracture are
      reported. Although these fractures are rare, surgeons should be aware of these
      atypical fracture patterns. Herein, the underlying physiology and the mechanism
      of injury of ankle fractures in children are discussed. LEVEL OF EVIDENCE:
      Therapeutic, Level IV, Case study.

PMID- 23863398
TI  - Preventing falls in the operating room: a technique tip for safely tilting the
      operating table.
AB  - BACKGROUND: Many articles have been published to address the topic of in-hospital
      falls; however, there is considerably less literature that focuses specifically
      on the topic of falls from the operating room table. The lay press and legal
      filings contain reports of such incidents, which can result in considerable
      morbidity, lawsuits, and occasional death. TECHNIQUE: When tilting the operating
      table, a simple technique for preventing falls is through the use of posts. Posts
      are regularly used during knee and hip arthroscopy to facilitate valgus
      positioning or access into the joint. These posts can be positioned below the
      axilla and at the level of the greater trochanter to supplement patient safety
      straps when tilting the table. DISCUSSION: Falls that occur during a hospital
      admission can lead to serious injury and prolonged hospital stays. Furthermore,
      falls that occur off the operating table are particularly disastrous and in some
      cases have resulted in death. Our proposed technique is simple and particularly
      useful for patients with large or small body habitus or when operating procedures
      necessitate significant tilting of the operating table. LEVELS OF EVIDENCE: Level
      V.

PMID- 23863399
TI  - Systems biology and the integration of mechanistic explanation and mathematical
      explanation.
AB  - The paper discusses how systems biology is working toward complex accounts that
      integrate explanation in terms of mechanisms and explanation by mathematical
      models-which some philosophers have viewed as rival models of explanation.
      Systems biology is an integrative approach, and it strongly relies on
      mathematical modeling. Philosophical accounts of mechanisms capture integrative
      in the sense of multilevel and multifield explanations, yet accounts of
      mechanistic explanation (as the analysis of a whole in terms of its structural
      parts and their qualitative interactions) have failed to address how a
      mathematical model could contribute to such explanations. I discuss how
      mathematical equations can be explanatorily relevant. Several cases from systems
      biology are discussed to illustrate the interplay between mechanistic research
      and mathematical modeling, and I point to questions about qualitative phenomena
      (rather than the explanation of quantitative details), where quantitative models
      are still indispensable to the explanation. Systems biology shows that a broader
      philosophical conception of mechanisms is needed, which takes into account
      functional-dynamical aspects, interaction in complex networks with feedback
      loops, system-wide functional properties such as distributed functionality and
      robustness, and a mechanism's ability to respond to perturbations (beyond its
      actual operation). I offer general conclusions for philosophical accounts of
      explanation. 

PMID- 23863400
TI  - Phage-directed synthesis of copper sulfide: structural and optical
      characterization.
AB  - The growth of crystalline copper sulfide using a viral template was investigated
      using sequential incubation in CuCl2 and Na2S precursors. Non-specific
      electrostatic attraction between a genetically-modified M13 bacteriophage and
      copper cations in the CuCl2 precursor caused phage agglomeration and bundle
      formation. Following the addition of Na2S, polydisperse nanocrystals 2-7 nm in
      size were found along the length of the viral scaffold. The structure of the
      copper sulfide material was identified as cubic anti-fluorite type Cu1.8S, space
      group Fm3[overline]m. Strong interband absorption was observed within the
      ultraviolet to visible range with an onset near 800 nm. Furthermore, free carrier
      absorption, associated with the localized surface plasmon resonance of the copper
      sulfide nanocrystals, was seen in the near infrared with absorbance maxima at
      1060 nm and 3000 nm, respectively.

PMID- 23863401
TI  - Increased body mass index is associated with earlier time to loss of response to
      infliximab in patients with inflammatory bowel disease.
AB  - BACKGROUND: Obesity is an emerging problem in the care of inflammatory bowel
      disease (IBD) patients and has been associated with a diminished response to
      adalimumab. Whether obesity influences the response to infliximab (IFX) is not
      known. METHODS: A retrospective cohort of 124 subjects with IBD initiating IFX,
      naive to biologic therapy, was identified. Subjects were stratified according to
      their weight and body mass index (BMI). The primary outcome was the first
      occurrence of an IBD flare defined as dose escalation of IFX, corticosteroid use,
      discontinuation of IFX, hospitalization, or surgery. Multivariable logistic
      regression was performed considering body mass and BMI as categorical and
      continuous variables. RESULTS: Obese (BMI > 30 kg/m) patients with Crohn's
      disease were more likely to have an IBD flare than nonobese patients (adjusted
      hazard ratio [HR]: 3.03, P < 0.001); overweight (BMI > 25 kg/m) patients with
      ulcerative colitis trended toward a similar observation (HR: 9.68, P = 0.06).
      When considered as continuous variables, increasing mass and BMI were associated
      with earlier IBD flare in both Crohn's disease (adjusted HR: 1.06 per unit
      increase in BMI [P = 0.02] and 1.02 per kg increase in body mass [P = 0.02]) and
      ulcerative colitis (adjusted HR: 1.3 per unit increase in BMI [P = 0.01] and 1.11
      per kg increase in body mass [P = 0.004]). CONCLUSIONS: Increased body weight is
      associated with an earlier time to loss of response to IFX in Crohn's disease and
      ulcerative colitis, a novel finding given that IFX is the only antitumor necrosis
      factor agent whose dosing reflects increased body weight.

PMID- 23863402
TI  - South African child deaths 1990-2011: have HIV services reversed the trend enough
      to meet Millennium Development Goal 4?
AB  - OBJECTIVE: To analyse trends in under-five mortality rate in South Africa (1990
      2011), particularly the contribution of AIDS deaths. METHODS: Three nationally
      used models for estimating AIDS deaths in children were systematically reviewed.
      The model outputs were compared with under-five mortality rate estimates for
      South Africa from two global estimation models. All estimates were compared with
      available empirical data. RESULTS: Differences between the models resulted in
      varying point estimates for under-five mortality but the trends were similar,
      with mortality increasing to a peak around 2005. The three models showing the
      contribution of AIDS suggest a maximum of 37-39% of child deaths were due to AIDS
      in 2004-2005 which has since declined. Although the rate of progress from 1990 is
      not the 4.4% needed to meet Millennium Development Goal 4 for child survival,
      South Africa's average annual rate of under-five mortality decline between 2006
      and 2011 was between 6.3 and 10.2%. CONCLUSION: In 2005, South Africa was one of
      only four countries globally with an under-five mortality rate higher than the
      1990 Millennium Development Goal baseline. Over the past 5 years, the country has
      achieved a rate of child mortality reduction exceeded by only three other
      countries. This rapid turnaround is likely due to scale-up of prevention of
      mother-to-child transmission of HIV, and to a lesser degree, the expanded roll
      out of antiretroviral therapy. Emphasis on these programmes must continue, but
      failure to address other aspects of care including integrated high-quality
      maternal and neonatal care means that the decline in child mortality could stall.

PMID- 23863403
TI  - Fundamental studies of the reproductive biology of the endangered persian onager
      (Equus hemionus onager) result in first wild equid offspring from artificial
      insemination.
AB  - We studied the Persian onager (Equus hemionus onager), an endangered equid
      subspecies. The objective was to characterize endocrine patterns and ovarian
      follicular dynamics of females as well as seminal traits and sperm sensitivity to
      cryopreservation in males as a prerequisite to testing the feasibility of
      artificial insemination (AI). Urinary progesterone and estrogen metabolite
      profiles were determined by enzyme immunoassay in 11 females. Serial
      ultrasonography of ovarian activity was performed for 2 mo in a subset of four
      females. Females were seasonally polyestrous (June-November). Ovarian morphometry
      via ultrasonography and urinary progesterone profiles were more reflective of
      reproductive events than urinary estrogen patterns, and preovulatory follicle
      size was smaller than reported for other equid species. There was evidence for
      lactational suppression of estrus for up to 1.5 yr in nursing dams.
      Electroejaculation allowed recovery of highly motile sperm from 7, anesthetized
      males on 57% of occasions. Spermatozoa, including motility and acrosomal
      integrity, were resilient to freeze-thawing. Artificial insemination was
      successful in 2 of 3 females following detection of a dominant follicle and
      deslorelin administration, resulting in births of a healthy female and male foal
      by using fresh/chilled and frozen/thawed sperm, respectively. 

PMID- 23863405
TI  - Identification of Ube2b as a novel target of androgen receptor in mouse sertoli
      cells.
AB  - Many genes are regulated by androgen and its receptor (AR), but the direct target
      genes of AR, especially those involved in spermatogenesis and male infertility,
      remain unclear. Here, we identified ubiquitin-conjugating enzyme E2B (Ube2b) as a
      critical target gene of AR. The expression of UBE2B was decreased in the testes
      of Sertoli cell AR knockout (S-AR(-/y)) mice analyzed by quantitative RT-PCR (qRT
      PCR) and immunofluorescence. The upregulation of Ube2b gene by testosterone was
      further demonstrated by Western blot and qRT-PCR in TM4 cells, a mouse Sertoli
      cell line. Moreover, luciferase assay, electrophoretic mobility shift assay, and
      chromatin immunoprecipitation assay validated that the ligand-bound AR activated
      Ube2b transcription via direct binding to the androgen-responsive element of the
      Ube2b promoter. In vitro analyses showed that testosterone increased UBE2B
      expression and activated H2A ubiquitylation, while downregulation of UBE2B
      blocked the testosterone-induced H2A ubiquitylation. The ubiquitylation of H2A
      was markedly decreased in the testes of S-AR(-/y) mice by immunohistochemistry.
      Digital gene expression analysis showed that 113 genes were significantly
      downregulated and 71 were upregulated by UBE2B in TM4 cells. These results
      suggest that Ube2b, as a direct AR transcriptional target in Sertoli cells,
      mediates the function of AR in spermatogenesis by promoting H2A ubiquitylation. 

PMID- 23863406
TI  - Identification of potential oviductal factors responsible for zona pellucida
      hardening and monospermy during fertilization in mammals.
AB  - Oviduct fluid increases the time required for digestion of the zona pellucida
      (ZP) by proteolytic enzymes (ZP hardening). This effect has been associated with
      levels of monospermy after in vitro fertilization (IVF) in the pig and cow, but
      the possible existence of a directly proportional relationship between hardening
      and monospermy remains unknown. To investigate whether variations in hardening of
      different oviductal fluids (OFs) are correlated with variations in levels of
      monospermy after IVF, porcine oocytes were incubated with three batches of OFs
      known to produce different ZP hardening effects (3, 7, and 25 min); after IVF,
      monospermy levels were 0%, 14.58% +/- 5.14%, and 35.14% +/- 7.95%, respectively.
      These results could partially explain the lack of polyspermy found during in vivo
      fertilization in pigs (with a hardened oviductal ZP) compared with levels found
      during IVF (with no hardened ZP). Using the bovine model, OF was fractionated by
      heparin affinity chromatography, and the hardening effect on the ZP was tested
      for each fraction obtained from a linear gradient of sodium chloride
      concentration. The highest effect was obtained with the fraction eluted with 0.4
      M sodium chloride. Fractions with high-level or low-level effects were processed
      by on-chip electrophoresis and high-performance liquid chromatography-tandem mass
      spectrometry. A list of potential proteins responsible for this effect includes
      OVGP1 and members of the HSP and PDI families. 

PMID- 23863404
TI  - Prophase I mouse oocytes are deficient in the ability to respond to fertilization
      by decreasing membrane receptivity to sperm and establishing a membrane block to
      polyspermy.
AB  - Changes occurring as the prophase I oocyte matures to metaphase II are critical
      for the acquisition of competence for normal egg activation and early
      embryogenesis. A prophase I oocyte cannot respond to a fertilizing sperm as a
      metaphase II egg does, including the ability to prevent polyspermic
      fertilization. Studies here demonstrate that the competence for the membrane
      block to polyspermy is deficient in prophase I mouse oocytes. In vitro
      fertilization experiments using identical insemination conditions result in
      monospermy in 87% of zona pellucida (ZP)-free metaphase II eggs, while 92% of ZP
      free prophase I oocytes have four or more fused sperm. The membrane block is
      associated with a postfertilization reduction in the capacity to support sperm
      binding, but this reduction in sperm-binding capacity is both less robust and
      slower to develop in fertilized prophase I oocytes. Fertilization of oocytes is
      dependent on the tetraspanin CD9, but little to no release of CD9 from the oocyte
      membrane is detected, suggesting that release of CD9-containing vesicles is not
      essential for fertilization. The deficiency in membrane block establishment in
      prophase I oocytes correlates with abnormalities in two postfertilization
      cytoskeletal changes: sperm-induced cortical remodeling that results in
      fertilization cone formation and a postfertilization increase in effective
      cortical tension. These data indicate that cortical maturation is a component of
      cytoplasmic maturation during the oocyte-to-egg transition and that the egg
      cortex has to be appropriately primed and tuned to be responsive to a fertilizing
      sperm. 

PMID- 23863408
TI  - Temporal and developmental-stage variation in the occurrence of mitotic errors in
      tripronuclear human preimplantation embryos.
AB  - Mitotic errors during early development of human preimplantation embryos are
      common, rendering a large proportion of embryos chromosomally mosaic. It is also
      known that the percentage of diploid cells in human diploid-aneuploid mosaic
      embryos is higher at the blastocyst than at the cleavage stage. In this study, we
      examined whether there is temporal and/or developmental-stage variation in the
      occurrence of mitotic errors in human preimplantation embryos from the first day
      of development onward using mitotically stable digynic tripronuclear human
      embryos as a model system. All the cells of the 114 digynic tripronuclear human
      preimplantation embryos included were analyzed by fluorescence in situ
      hybridization for chromosomes 1, 13, 16, 17, 18, 21, X, and Y. Embryos were
      grouped according to day of development (1-6) and developmental stage (2-cell to
      blastocyst stage). The possibility of a mitotic error was highest in the first
      and second mitotic divisions. The percentage of cells with mitotic errors
      increased during preimplantation development and was highest at the 9-16 cell
      stage (76%, P = 0.027). Thereafter, the percentage of cells with mitotic errors
      decreased to 64% at the morula and 56% at the blastocyst stage. The pattern found
      correlates with the activation of the embryonic genome at the 8-16 cell stage. A
      better insight in the timing of occurrence of mitotic errors in human
      preimplantation embryos could help in understanding and prevention of these
      errors and is relevant in the context of PGS. 

PMID- 23863407
TI  - A requirement for fatty acid oxidation in the hormone-induced meiotic maturation
      of mouse oocytes.
AB  - We have previously shown that fatty acid oxidation (FAO) is required for AMP
      activated protein kinase (PRKA)-induced maturation in vitro. In the present
      study, we have further investigated the role of this metabolic pathway in hormone
      induced meiotic maturation. Incorporating an assay with (3)H-palmitic acid as the
      substrate, we first examined the effect of PRKA activators on FAO levels. There
      was a significant stimulation of FAO in cumulus cell-enclosed oocytes (CEO)
      treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and RSVA405.
      In denuded oocytes (DO), AICAR stimulated FAO only in the presence of carnitine,
      the molecule that facilitates fatty acyl CoA entry into the mitochondria. The
      carnitine palmitoyltransferase 1 activator C75 successfully stimulated FAO in
      CEO. All three of these activators trigger germinal vesicle breakdown. Meiotic
      resumption induced by follicle-stimulating hormone (FSH) or amphiregulin was
      completely inhibited by the FAO inhibitors etomoxir, mercaptoacetate, and malonyl
      CoA. Importantly, FAO was increased in CEO stimulated by FSH and epidermal growth
      factor, and this increase was blocked by FAO inhibitors. Moreover, compound C, a
      PRKA inhibitor, prevented the FSH-induced increase in FAO. Both carnitine and
      palmitic acid augmented hormonal induction of maturation. In a more physiological
      setting, etomoxir eliminated human chorionic gonadotropin (hCG)-induced
      maturation in follicle-enclosed oocytes. In addition, CEO and DO from hCG-treated
      mice displayed an etomoxir-sensitive increase in FAO, indicating that this
      pathway was stimulated during in vivo meiotic resumption. Taken together, our
      data indicate that hormone-induced maturation in mice requires a PRKA-dependent
      increase in FAO. 

PMID- 23863410
TI  - Hip range of motion in children.

PMID- 23863409
TI  - Altered expression of enzymes regulating the activity of endothelin-1 in the
      lower segment of the human amnion during labor.
AB  - The level of endothelin (ET)-1, a uterotonin, increases in amniotic fluid during
      labor. The known metallopeptidases include ET-converting enzyme (ECE), which
      converts inactive precursor to potent ET-1, and neutral endopeptidase (NEP),
      which inactivates ET-1. These enzymes are present in fetal membranes, and the
      aims of this study were to establish the protein expression of the enzymes within
      the amnion of human fetal membranes. Expressions were compared between amnions
      obtained before and after term labor using a Western blot analysis and enzyme
      linked immunosorbent assay, respectively. The localization of these enzymes was
      determined using immunohistochemistry. The protein expression of the enzymes and
      output of bioactive ET-1 in human amnion epithelial cells (HAECs) and mesenchymal
      cells (HAMCs) were investigated with and without proinflammatory cytokines,
      oxytocin, and prostaglandin treatment. The effects of sphingosine-1-phosphate
      (S1P), a bioactive lipid, were also examined. The protein expression of ECE-1 was
      significantly increased (P < 0.01), whereas that of NEP was significantly
      decreased, followed by increased ET-1 (P < 0.01), in the amnion obtained after
      labor (P < 0.01). HAECs and HAMCs primarily expressed ECE-1 and NEP,
      respectively. The protein expression of ECE-1 was significantly induced (P <
      0.01). However, the NEP levels were significantly reduced (P < 0.05) by treatment
      with TNFalpha and IL1beta followed by the 7.5-fold and 6.5-fold increase of ET-1
      (P < 0.01), respectively, in the HAECs. ET-1 was increased 2-fold by S1P (P <
      0.01). These results suggest that the altered expression of enzymes regulating
      the activity of ET-1 during parturition is controlled by inflammatory cytokines. 

PMID- 23863411
TI  - Musculoskeletal functional outcomes in children with osteogenesis imperfecta:
      associations with disease severity and pamidronate therapy.
AB  - BACKGROUND: Intravenous pamidronate has been used off-label in the treatment of
      severe osteogenesis imperfecta (OI) for almost 20 years. Previous studies have
      found correlations between function and bone density in patients with OI, but
      have not studied the functional outcomes of these patients after bisphosphonate
      therapy with a validated outcome measure. The goal of this investigation is to
      describe the functionality and comfort of children with OI. We hypothesize that
      function is impaired in children with severe OI as measured using the Pediatric
      Outcomes Data Collection Instrument (PODCI) and that improvements in the function
      of children with severe OI may be observed in association with intravenous
      bisphosphonate therapy. METHODS: A total of 25 patients with OI were evaluated,
      of those, 15 received pamidronate therapy. Children with >2 long bone fractures
      per year were classified as having severe OI and were eligible for pamidronate
      therapy. Functional evaluation was performed using the PODCI for children who
      qualified for pamidronate therapy (severe OI) and those who did not qualify for
      pamidronate therapy (mild OI). PODCI evaluation was also performed after
      treatment with pamidronate in the group that qualified for pamidronate therapy.
      RESULTS: There was a statistically significant difference at baseline between
      patients with "mild" and "severe" OI in the sports/physical functioning scale
      (P=0.0032). Among the children who received bisphosphonate therapy, PODCI scores
      in the sports/physical functioning domain were significantly improved after
      pamidronate therapy (P=0.0364). CONCLUSIONS: This study indicates that children
      with mild forms of OI can be differentiated from their more severe counterparts
      by their ability to participate in high-level play activities. Furthermore,
      patients with "severe" OI show a significant improvement in their ability to
      participate in high-level play after 1 year of pamidronate. LEVEL OF EVIDENCE:
      Level IV.

PMID- 23863412
TI  - Results of single-staged rotational osteotomy in a child with congenital proximal
      radioulnar synostosis: subjective and objective evaluation.
AB  - BACKGROUND: For congenital proximal radioulnar synostosis, both conservative and
      operative treatments have been described. Most of the studies describing surgical
      interventions are based on subjective evaluation of the forearm function and have
      used severe degree of forearm pronation as an indication for surgery. This study
      describes a single-staged rotational osteotomy of the proximal third ulna and
      distal third radius. The aim of the study was to assess the utility of the
      described surgical procedure by subjective and objective evaluations of the
      forearm function. METHODS: Forty-eight children with congenital proximal
      radioulnar synostosis were evaluated by subjective and objective assessments and
      were followed up prospectively. Subjective evaluation consisted of a set of 12
      questions regarding the basic activities of life. Objective evaluation was made
      using the Jebsen-Taylor hand-function test and a classification system used by
      Failla and colleagues for 15 tasks described by Morrey and colleagues. Eleven
      children were treated conservatively. Thirty-six children underwent a single
      staged rotational osteotomy of the proximal third ulna and distal third radius.
      After surgery, the evaluations were repeated. The mean age at surgery was 8.6+/
      3.7 years, and the mean postoperative follow-up period was 54+/-13 months.
      RESULTS: All operated forearms showed a statistically significant improvement in
      functioning after surgery as per the subjective and objective evaluations. The
      mean time taken to carry out all activities before surgery was 47.7+10.0 seconds,
      which significantly reduced to 33.3+6.6 seconds after surgery (P=0.0001) as per
      the results of the Jebsen-Taylor hand-function test. All good (n=19) and fair
      (n=11) results were converted to excellent (n=30) after surgery as per the
      modified Failla classification. There were no neurovascular injuries as compared
      with other published techniques. Only 1 child had delayed union, and 1 had
      persistent dorsal angulation at the radial osteotomy site. CONCLUSIONS: For
      patients with congenital radioulnar synostosis and pronation deformity
      interfering with function and quality of life, the single-staged rotational
      osteotomy of the radius and ulna is a good alternative procedure. LEVEL OF
      EVIDENCE: Level IV--therapeutic.

PMID- 23863413
TI  - The effect of rod diameter on correction of adolescent idiopathic scoliosis at
      two years follow-up.
AB  - STUDY DESIGN: The review of multicenter national pediatric scoliosis database.
      OBJECTIVE: The purpose of this study was to compare the radiographic outcomes of
      patients who underwent scoliosis surgery utilizing different rod diameter
      constructs by the posterior approach. BACKGROUND: Little attention has
      specifically been focused on the effect of rod diameter on correction of spinal
      deformity after posterior spinal instrumentation and fusion in children with
      adolescent idiopathic scoliosis (AIS). METHODS: The review of national database
      comprised of 1125 patients, of which 352 patients had a minimum follow-up of 2
      years. Of these, 163 patients received 5.5 mm and 189 patients received 6.35 mm
      diameter rods for posterior spinal instrumentation. RESULTS: The 6.35 mm rods
      were used more often for patients who were male, taller, heavier, with larger
      coronal curves, and more flexible curves. Larger diameter rods were also more
      likely to be stainless steel, implanted with an increased number of implants per
      level, and an increased number of pedicle screws used on the concavity of the
      curve. Univariate analysis of coronal curve showed a significant difference
      between 5.5 and 6.35 mm rods in correction (67.0% vs. 57.3%) at 2 years.
      Multivariate analysis revealed that the most significant factors affecting
      coronal curve correction at 2 years were rod diameter, the patient's preoperative
      coronal major curve and flexibility, and the implant density. In the sagittal
      plane, preoperative sagittal curve and rod diameter are the predictors of
      sagittal correction at 2 years. CONCLUSIONS: The study did not support our
      hypothesis that larger rods would be associated with a greater correction of
      frontal and sagittal plane in patients with AIS. In addition to rod diameter,
      implant density and the inherent flexibility and deformity of the patient were
      found to be influential factors contributing for the correction and maintenance
      of coronal and sagittal curves in AIS.

PMID- 23863414
TI  - Medial ulnar collateral ligament origin in children and adolescents: an MRI
      anatomic study.
AB  - BACKGROUND: The medial ulnar collateral ligament (MUCL) is the primary stabilizer
      against valgus stress on the elbow. The anatomy of the 3 bundles of the MUCL has
      been well studied in adults, but our review of the English literature found no
      study evaluating the origin of the MUCL in a large group of asymptomatic,
      skeletally immature elbows as it relates to the medial epicondylar physis.
      METHODS: Magnetic resonance T1-coronal images of 44 skeletally immature elbows
      (ages 5 to 17 y) with no history of fracture were evaluated by 2 independent
      musculoskeletal radiologists, a board-certified orthopaedic surgeon with
      fellowship training in pediatric orthopaedics, and an orthopaedic surgery
      resident. The location of the origin of the anterior bundle of the MUCL (aMUCL)
      was identified and its distance from the medial epicondylar physis was measured.
      RESULTS: All 44 images showed that the aMUCL attached either on or medial to the
      medial epicondylar physis. The average distance from the origin of the aMUCL to
      the medial epicondylar physis was 3.1 mm. There was no statistically significant
      relationship between age and location of the aMUCL insertion relative to the
      physis (P=0.183). CONCLUSIONS: In the skeletally immature elbow, the aMUCL
      originates medial to the medial epicondylar physis. CLINICAL RELEVANCE: Although
      treatment of medial epicondylar humeral fractures remains controversial,
      understanding the relationship between the aMUCL and the medial epicondylar
      physis may be helpful in making decisions regarding fracture management.

PMID- 23863415
TI  - Internal consistency and validity of the QuickDASH instrument for upper extremity
      injuries in older children.
AB  - BACKGROUND: The short version of the Disabilities of the Arm, Shoulder and Hand
      instrument (QuickDASH) has been shown to be a valid, reliable, and responsive
      measure of upper extremity function in adults. However, the psychometric
      properties of the QuickDASH for younger patients have not been well established.
      The purpose of this study was to evaluate the internal consistency and validity
      of the QuickDASH for use with older children and adolescents. METHODS: The
      QuickDASH and PedsQL instruments were administered to 149 patients grouped into
      ages 8 to 12 and 13 to 18 years. RESULTS: Item response analysis showed a low SE
      of measurement (0.06) and a high coefficient alpha (0.91), suggesting high
      internal consistency among items. The QuickDASH was found to be a predictor of
      PedsQL score for both groups (P<0.01). CONCLUSIONS: The results indicate that the
      QuickDASH is a consistent and valid instrument for older children and adolescents
      with upper extremity pathology. LEVEL OF EVIDENCE: III, case series.

PMID- 23863416
TI  - Ammonium nitrogen removal in batch cultures treating digested piggery wastewater
      with microalgae Oedogonium sp.
AB  - Due to the nutrient characteristics of the high concentration of available
      ammonium in digested piggery wastewater (DPW), microalgae can be used to treat
      DPW before its final discharge. Four green microalgae (Hydrodictyaceae
      reticulatum Lag, Scenedesmus obliquus, Oedogonium sp. and Chlorella pyrenoidosa)
      and three blue-green algae (Anabaena flos-aquae, Oscillatoria amoena Gom and
      Spirulina platensis) were used to remove the nutrients (N, P, C), especially
      ammonium nitrogen (NH4(+)-N), from diluted DPW with 300 mg/L algae density in
      batch tests. The microalgae with the best NH4(+)-N nutrient removal was then
      selected for further optimization of the variables to improve NH4(+)-N removal
      efficiency using a central composite design (CCD) experiment. Taking into account
      the nutrient removal efficiency, Oedogonium sp. showed the best performance
      (reduction of 95.9% NH4(+)-N, 92.9% total phosphorus (TP) and 62.5% chemical
      oxygen demand (COD)) based on the results of the batch tests. The CCD results
      suggested that the optimal values of variables were initial Oedogonium sp.
      density of 399.2 mg/L and DPW diluted by 16.3, while the predicted value of
      NH4(+)-N removal efficiency obtained was 97.0%. 

PMID- 23863417
TI  - Stability of nano-sized titanium dioxide in an aqueous environment: effects of
      pH, dissolved organic matter and divalent cations.
AB  - Nano-sized titanium dioxide in the aquatic environment has a potential impact on
      the environment and human health. In this study, the impact of pH value,
      dissolved organic matter (DOM) and divalent cations (Ca(2+)) on the stability of
      titanium dioxide nanoparticles (nano-TiO2) in an aqueous environment was
      investigated in batch tests. The results showed that the particle size of nano
      TiO2 was not sensitive to pH value but was inversely proportional to zeta
      potential. The nano-TiO2 becomes more stable with surface zeta potential,
      accompanied by small particle size and high dispersion. In the presence of DOM,
      the particle size was smaller and the stability of nano-TiO2 could be enhanced.
      This might be a synergistic effect of the ligand exchange and electrostatic
      force. Particle size increased with the addition of Ca(2+) and the stability
      decreased. 

PMID- 23863418
TI  - Going for mainstream deammonification from bench to full scale for maximized
      resource efficiency.
AB  - A three-pronged coordinated research effort was undertaken by cooperating
      utilities at three different experimental scales investigating bioaugmentation,
      enrichment and performance of anammox organisms in mainstream treatment. Two
      major technological components were applied: density-based sludge wasting by a
      selective cyclone to retain anammox granules and intermittent aeration to repress
      nitrite oxidizers. This paper evaluates process conditions and operation modes to
      direct more nitrogen to the resource-saving metabolic route of deammonification. 

PMID- 23863419
TI  - Effects of lipid composition on partitioning of fullerene between water and lipid
      membranes.
AB  - Fullerene partition coefficients (Klipw) between water and solid supported lipid
      membranes were determined for membranes of various lipid types and composition
      over a range of temperatures. The log Klipw (L/kg) values for fullerene, which
      range from 3.1 to 5.3, depend on the lipid type in the lipid membranes. Partition
      coefficients increased with increasing temperature, increasing acyl chain length
      of unsaturated lipids. The results indicate that lipid composition is a critical
      factor for bioconcentration of fullerene. 

PMID- 23863420
TI  - Add Control: plant virtualization for control solutions in WWTP.
AB  - This paper summarizes part of the research work carried out in the Add Control
      project, which proposes an extension of the wastewater treatment plant (WWTP)
      models and modelling architectures used in traditional WWTP simulation tools,
      addressing, in addition to the classical mass transformations (transport, physico
      chemical phenomena, biological reactions), all the instrumentation, actuation and
      automation & control components (sensors, actuators, controllers), considering
      their real behaviour (signal delays, noise, failures and power consumption of
      actuators). Its ultimate objective is to allow a rapid transition from the
      simulation of the control strategy to its implementation at full-scale plants.
      Thus, this paper presents the application of the Add Control simulation platform
      for the design and implementation of new control strategies at the WWTP of
      Mekolalde. 

PMID- 23863421
TI  - Evaluation of E. coli biofilm as a protective barrier against microbiologically
      influenced deterioration of concrete (MICD) under mesophilic temperatures.
AB  - In this study, Escherichia coli DH5alpha biofilm was evaluated for its potential
      to control and minimize microbiologically influenced concrete deterioration
      (MICD) under mesophilic temperatures (37  degrees C). Escherichia coli DH5alpha
      biofilm was first grown on Portland cement mortar disks for 8 days. Mortar disks
      were then exposed to two different types of sulfur oxidizing bacteria (SOB)
      (Thiobacillus neapolitanus and Thiobacillus thiooxidans), which use sulfur
      compounds as substrate and oxidize them to sulfate and sulfuric acid. The
      effectiveness of the biofilm against MICD was evaluated by measuring pH, sulfate,
      calcium concentrations in the reactors and surface analysis of the mortar samples
      using X-ray diffraction and visual inspection. Overall, the results indicate that
      the E. coli DH5alpha biofilm showed good protection against MICD induced by SOB
      at 37  degrees C. 

PMID- 23863422
TI  - Microorganism inactivation by an ozonation step optimized for micropollutant
      removal from tertiary effluent.
AB  - This paper demonstrates the additional benefit of the microbicidal efficacy of an
      ozonation plant implemented for micropollutant removal from tertiary effluent.
      Due to the low amount of viruses and protozoa in the tertiary effluent,
      bacteriophage MS2 and spores of Bacillus subtilis were dosed as surrogates. At
      specific ozone consumptions of 0.6 and 0.9 g O3/g dissolved organic carbon (DOC)
      a 2-log colony forming unit (CFU) reduction was achieved for indigenous
      Escherichia coli and enterococci, and the limits of the European bathing water
      directive for the excellent quality of inland waters were met. Higher removal was
      impeded by the shielding effect of suspended solids in the effluent, which
      implies the combination of ozonation with a preceding filtration step if higher
      microbicidal performances are required. The surrogate virus MS2 was reduced by 4
      5 log while no significant inactivation was detected for B. subtilis spores.
      Additionally, the impact of ozonation on the biochemical oxygen demand (BOD) was
      studied. The BOD5 measurement was not adversely affected despite the reduced
      concentration of microorganisms after ozonation. The intrinsic increase in BOD5
      averaged 15% at 0.6-0.7 g O3/g DOC. The impact of the projected increase on the
      surface water quality is generally not considered a problem but has to be
      assessed on a case-by-case approach. 

PMID- 23863423
TI  - Parameter estimation for eutrophication models in reservoirs.
AB  - Excessive eutrophication is a major water quality issue in lakes and reservoirs
      worldwide. This complex biological process can lead to serious water quality
      problems. Although it can be adequately addressed by applying sophisticated
      mathematical models, the application of these tools in a reservoir management
      context requires significant amounts of data and large computation times. This
      work presents a simple primary production model and a calibration procedure that
      can efficiently be used in operational reservoir management frameworks. It
      considers four state variables: herbivorous zooplankton, algae (measured as
      chlorophyll-a pigment), phosphorous and nitrogen. The model was applied to a set
      of Portuguese reservoirs. We apply the model to 23 Portuguese reservoirs in two
      different calibration settings. This research work presents the results of the
      estimation of model parameters. 

PMID- 23863424
TI  - Physically based closed-form expression for the bimodal unsaturated hydraulic
      conductivity function.
AB  - Simulation of flow and contaminant transport through the vadose zone requires
      accurate parameterization of the soil hydraulic properties. This requirement is
      particularly important for soils with a complex structure. In the present study,
      a physically based closed-form expression for the bimodal unsaturated hydraulic
      conductivity function is proposed for soils with bimodal pore-size distribution.
      It combines the bimodal representation of the soil-water characteristic curve
      (SWCC) function of Liu with the conductivity representation model of Mualem. The
      proposed equations are defined by parameters that have physical significance,
      which can be related to the properties of the materials. Experimental data for
      the representation of bimodal SWCCs and corresponding hydraulic conductivity
      curves were used to demonstrate the applicability of the proposed functions. The
      proposed approaches resulted in good agreement with experimental data. These
      functions can potentially be used as an effective tool for identifying hydraulic
      porosities in mediums with a complex structure. 

PMID- 23863425
TI  - Influence of earthworm Eisenia fetida on Iris pseudacorus's photosynthetic
      characteristics, evapotranspiration losses and purifying capacity in constructed
      wetland systems.
AB  - Four constructed wetland systems were studied to investigate the effects of
      adding Eisenia fetida on the purifying capacity of constructed wetlands. Addition
      of E. fetida increased the photosynthetic rate (Pn), transpiration rate (Tr) and
      chlorophyll meter value of leaves of Iris pseudacorus L. in the constructed
      wetlands by 16, 35 and 7%, respectively. Compared with the substrate only system,
      evapotranspiration losses were increased by 8, 48 and 56% for the wetland systems
      with substrate and E. fetida, with substrate and I. pseudacorus, and with
      substrate, I. pseudacorus and E. fetida, respectively. Addition of E. fetida to
      the substrate only and substrate and plant wetland systems decreased the
      substrate bulk density by 3 and 6%, respectively. The addition of E. fetida to
      the system with substrate and plants increased the removal efficiency of chemical
      oxygen demand (CODMn), total nitrogen (TN) and total phosphorus by 5, 7 and 22%,
      respectively. Evapotranspiration losses were significantly positively correlated
      with the removal efficiency of CODMn (P < 0.01). The significantly negative
      correlation between the removal efficiency TN and bulk density was found (P <
      0.05). Therefore, E. fetida could stimulate I. pseudacorus growth and improve the
      substrate bulk density in the constructed wetland, resulting in enhanced
      purifying capacity. 

PMID- 23863426
TI  - Synthesis of tetrakis (hydroxymethyl) phosphonium chloride by high-concentration
      phosphine in industrial off-gas.
AB  - With increasing consumption of phosphate rock and acceleration of global
      phosphate production, the shortage of phosphate resources is increasing with the
      development and utilization of phosphate. China's Ministry of Land and Resources
      has classified phosphate as a mineral that cannot meet China's growing demand for
      phosphate rock in 2010. The phosphorus chemical industry is one of the important
      economic pillars for Yunnan province. Yellow phosphorus production in enterprises
      has led to a significant increase in the amount of phosphorus sludge. This paper
      focuses on phosphine generation in the process of phosphoric sludge utilization,
      where the flame retardant tetrakis (hydroxymethyl) phosphonium chloride (THPC) is
      synthesized by high concentrations of phosphine. The optimum conditions are
      determined at a space velocity of 150 h(-1), a reaction temperature of 60 
      degrees C, 0.75 g of catalyst, and a ratio of raw materials of 4:1. Because of
      the catalytic oxidation of copper chloride (CuCl2), the synthesis of THPC was
      accelerated significantly. In conclusion, THPC can be efficiently synthesized
      under optimal conditions and with CuCl2 as a catalyst. 

PMID- 23863427
TI  - Phytoplankton and bacterioplankton abundances and community dynamics in Lake
      Erhai.
AB  - The composition and seasonal variation of the phytoplankton and bacterioplankton
      community were investigated, and SPSS and redundancy analysis (RDA) were used to
      explore the relationship between the phytoplankton and bacterioplankton community
      dynamics in the typical plateau Lake of Lake Erhai from July 2009 to April 2010.
      Obvious seasonal variation of phytoplankton was observed, and the abundance of
      phytoplankton ranged from 2.02 * 10(6) to 57.9 * 10(6) cells/L. The dominant
      species in autumn and summer was Microcystis sp., Psephonema aenigmaticum Skuja
      was dominant in winter, and Microcystis sp., Aphanizonmenon flos-aquae,
      Asterionella sp., P. aenigmaticum, etc. were dominant in spring. The abundance of
      bacterioplankton in the whole lake changed between 1.93 * 10(9) and 4.61 * 10(9)
      cells/L showing distinct seasonal variation characteristics. The results of
      correlation and RDA indicated that the abundance and community diversity of
      bacterioplankton were significantly correlated with the abundance of
      phytoplankton, and the group of Bacteroidetes had obvious correlation with
      Microcystis sp. and other cyanobacteria, which might have some links with the
      harmful algal blooms in Lake Erhai. Further research is needed to study the
      mechanisms of interactions between phytoplankton and bacterioplankton
      communities. 

PMID- 23863428
TI  - Modelling of point and diffuse pollution: application of the Moneris model in the
      Ipojuca river basin, Pernambuco State, Brazil.
AB  - Emissions of pollutants and nutrients are causing several problems in aquatic
      ecosystems, and in general an excess of nutrients, specifically nitrogen and
      phosphorus, is responsible for the eutrophication process in water bodies. In
      most developed countries, more attention is given to diffuse pollution because
      problems with point pollution have already been solved. In many non-developed
      countries basic data for point and diffuse pollution are not available. The focus
      of the presented studies is to quantify nutrient emissions from point and diffuse
      sources in the Ipojuca river basin, Pernambuco State, Brazil, using the Moneris
      model (Modelling Nutrient Emissions in River Systems). This model has been
      developed in Germany and has already been implemented in more than 600 river
      basins. The model is mainly based on river flow, water quality and geographical
      information system data. According to the Moneris model results, untreated
      domestic sewage is the major source of nutrients in the Ipojuca river basin. The
      Moneris model has shown itself to be a useful tool that allows the identification
      and quantification of point and diffuse nutrient sources, thus enabling the
      adoption of measures to reduce them. The Moneris model, conducted for the first
      time in a tropical river basin with intermittent flow, can be used as a reference
      for implementation in other watersheds. 

PMID- 23863429
TI  - Comparison of nutrient-removing microbial communities in activated sludge from
      full-scale MBRs and conventional plants.
AB  - The composition of nutrient-removing microbial communities in five full-scale
      membrane bioreactors (MBRs) was investigated using fluorescence in situ
      hybridization and 16S rRNA pyrosequencing and compared to similar analyses of
      conventional activated sludge (CAS) communities. The communities were highly
      similar but some genera that are always present in enhanced biological phosphorus
      removal (EBPR) (core groups) were absent in the MBRs. The overall phylogenetic
      similarity of the communities indicated that these differences were primarily
      closely related groups. More research is needed to establish the operational
      significance of the observed differences between MBR and CAS sludge. 

PMID- 23863430
TI  - Comparison between InfoWorks hydraulic results and a physical model of an urban
      drainage system.
AB  - Urban drainage systems are frequently analysed using hydraulic modelling software
      packages such as InfoWorks CS or MIKE-Urban. The use of such modelling tools
      allows the evaluation of sewer capacity and the likelihood and impact of pluvial
      flood events. Models can also be used to plan major investments such as
      increasing storage capacity or the implementation of sustainable urban drainage
      systems. In spite of their widespread use, when applied to flooding the results
      of hydraulic models are rarely compared with field or laboratory (i.e. physical
      modelling) data. This is largely due to the time and expense required to collect
      reliable empirical data sets. This paper describes a laboratory facility which
      will enable an urban flood model to be verified and generic approaches to be
      built. Results are presented from the first phase of testing, which compares the
      sub-surface hydraulic performance of a physical scale model of a sewer network in
      Yorkshire, UK, with downscaled results from a calibrated 1D InfoWorks hydraulic
      model of the site. A variety of real rainfall events measured in the catchment
      over a period of 15 months (April 2008-June 2009) have been both hydraulically
      modelled and reproduced in the physical model. In most cases a comparison of flow
      hydrographs generated in both hydraulic and physical models shows good agreement
      in terms of velocities which pass through the system. 

PMID- 23863431
TI  - The impact of chlorine disinfection on biochemical oxygen demand levels in
      chemically enhanced primary treatment effluent.
AB  - The response trends of biochemical oxygen demand (BOD) and organic strength after
      the chlorination/dechlorination process were explored through a 2-year, 5-month
      chemically enhanced primary treatment (CEPT) effluent onsite monitoring program
      and a 2-month laboratory-scale study. The monitoring results showed that better
      instantaneous mixing at the chlorine injection point reduced the effect of
      chlorination/dechlorination on the 5-day BOD levels. The laboratory study results
      demonstrated that chlorination did not change the particle size distribution,
      dissolved organic carbon, or chemical oxygen demand of the organic content of the
      effluent. Nevertheless, chlorination/dechlorination strongly affected the BOD
      measurement when nitrification was inhibited by changing
      bioactivity/biodegradation rates. 

PMID- 23863432
TI  - Phosphatase activity and specific methanogenic activity in an anaerobic reactor
      treating sludge from a brackish recirculation aquaculture system.
AB  - Anaerobic treatment of high salinity sludge from marine/brackish recirculation
      aquaculture systems is potentially limited by inhibition of enzymatic activities
      and cell lysis resulting from high osmotic pressures. To further address these
      limitations the following investigations were conducted: effect of salinity on
      phosphatase activity (PA), soluble microbial products (SMP) production, and
      presence of extracellular polymeric substances (EPS); effect of iron (III)
      chloride (FeCl3) on PA and specific methanogenic activity (SMA); effect of
      addition of the compatible solute glycine betaine (GB) and potassium on PA, as
      well as on SMP and EPS production, all under saline conditions. The results show
      that salinity has different effects on PA of anaerobes under starvation and
      feeding conditions. FeCl3 increased the SMA of the sludge by 22.5% at 100 mg
      FeCl3/L compared with a control group (0 mg FeCl3/L). Furthermore, results of
      analysis of variance tests show that betaine increased the polysaccharide content
      of EPS and polypeptide content of SMP. However, addition of 1 mM potassium
      chloride did not show a significant effect on EPS and SMP composition. In
      conclusion, anaerobic digestion of salty sludges from a brackish aquaculture
      recirculation system may not be negatively affected by FeCl3 addition to
      concentrate waste streams, whereas GB boosts the production of SMP and EPS. 

PMID- 23863433
TI  - Two-stage anaerobic fluidized-bed membrane bioreactor treatment of settled
      domestic wastewater.
AB  - A two-stage anaerobic fluidized-bed membrane bioreactor (SAF-MBR) system was
      applied for the treatment of primary-settled domestic wastewater that was further
      pre-treated by either 10 MUm filtration or 1 mm screening. While the different
      pre-treatment options resulted in different influent qualities, the effluent
      qualities were quite similar. In both cases at a total hydraulic retention time
      of 2.3 h and 25  degrees C, chemical oxygen demand and biochemical oxygen demand
      (BOD5) removals were 84-91% and 92-94%, with effluent concentrations lower than
      25 and 7 mg/L, respectively. With a membrane flux of 6-12 L/m(2)/h, trans
      membrane pressure remained below 0.2 bar during 310 d of continuous operation
      without need for membrane chemical cleaning or backwashing. Biosolids production
      was estimated to be 0.028-0.049 g volatile suspended solids/g BOD5, which is far
      less than that with comparable aerobic processes. Electrical energy production
      from combined heat and power utilization of the total methane produced (gaseous
      and dissolved) was estimated to be more than sufficient for total system
      operation. 

PMID- 23863434
TI  - Assessment of nitrogen and phosphorus removal in an intermittently aerated
      sequencing batch reactor (IASBR) and a sequencing batch reactor (SBR).
AB  - Biological nitrogen and phosphorus removal was investigated in an intermittently
      aerated sequencing batch reactor (IASBR) and a sequencing batch reactor (SBR).
      The removal efficiencies of ammonium-nitrogen (NH4(+)-N) were 100% in both
      reactors in steady operation state. The total nitrogen (TN) removal efficiencies
      were 90.4% in the IASBR and 79.3% in the SBR, while the total phosphorus (TP)
      removal efficiencies were 88.8% in the IASBR and 82.3% in the SBR. The
      efficiencies of simultaneous nitrification and denitrification (SND) were 90.4%
      in the IASBR and 79.3% in the SBR, indicating that the IASBR was more efficient
      than the SBR in SND. The sludge in the IASBR had a P release capability of 16.6
      mg P/g VSS (volatile suspended solids) but only 7.5 mg P/g VSS in the SBR. 

PMID- 23863435
TI  - Modeling the groundwater recharge in karst aquifers by using a reservoir model.
AB  - The estimation of the groundwater recharge in a karstic system becomes an
      important challenge due to the great hydrodynamic variability in both time and
      space. This paper proposes a two reservoir conceptual model to simulate inflow
      into both the conduit system and the fissure network system based on the analysis
      of the spring hydrograph. The structure of the model and the governing equations
      are proposed on the basis of the physical considerations, with the assumption
      that flow at the outlet of the reservoirs obeys a linear threshold function. The
      model is applied on the Houzhai karstic underground river basin where it
      successfully reflects the temporal recharge distribution. The simulated
      accumulation recharge is 34.29 mm, which is reasonable in relation to the actual
      rainfall of 92.8 mm. The variations of water volume in two reservoirs represent
      the storage and transform characteristics of the karst aquifer system. However,
      this model is particularly well suited to simulate the recharge event after
      intensive rainfall. 

PMID- 23863436
TI  - Methane production and hydrolysis kinetics in the anaerobic degradation of
      wastewater screenings.
AB  - Anaerobic biodegradability and hydrolysis rates of wastewater screenings were
      determined using the biochemical methane potential test at 37  degrees C. The
      extent and rate of screenings conversion to methane of this complex and
      particulate substrate were investigated and since two stages of hydrolysis were
      identified, corresponding to the different types of materials in screenings, a
      linear and non-linear model was used. No accumulation of intermediary products
      was observed and so it was possible to use the methane production rate and a
      linear model to estimate the hydrolysis rate in the first phase of hydrolysis.
      The measured values of 0.061-0.127 d(-1) are in the range reported for other
      comparable organic wastes. It was also observed that the inoculum-to-substrate
      ratio has a large impact on methane production rate of screenings. The difference
      in biodegradation rates from the materials in screenings and the overall
      hydrolysis could be represented by the modified Gompertz non-linear model which
      was able to describe the methane production rate of screenings with a high
      confidence. Screenings were found to have 52% biodegradability on average and
      this shows the potential for volatile solids destruction. A two-stage process
      with an improved hydrolysis rate is proposed to ensure that the full potential of
      the material is exploited. 

PMID- 23863437
TI  - Effect of environmental factors on allelopathic inhibition of Microcystis
      aeruginosa by berberine.
AB  - To understand how environmental conditions affect the allelopathic inhibition of
      toxic Microcystis aeruginosa by berberine, the independent effects of some
      environmental factors, including temperature, light, and aeration, on the growth
      and extracellular microcystin (MC) content of M. aeruginosa (FACHB 905) treated
      with 0.000 and 0.001% (w/v) berberine were investigated. The results showed that
      higher temperature and light density, and aeration in daytime were beneficial for
      the growth of M. aeruginosa under the measured environmental conditions. The
      allelopathic effects of berberine on M. aeruginosa were closely associated with
      the environmental conditions. Berberine had the best inhibitory effects when
      temperature, light and aeration were more optimal for growth. In darkness, no
      changes in the density of M. aeruginosa were observed with the prolongation of
      culture time and berberine could hardly exhibit algicidal effects. Disturbance in
      the photosynthesis process might be one of the main reasons responsible for
      algicidal function. Berberine could increase extracellular MC contents
      significantly via killing and lyzing algal cells. Other treatments coupled with
      berberine needed to be carried out to degrade or remove MC released from
      berberine-killed algal cells. 

PMID- 23863438
TI  - Verification of flood damage modelling using insurance data.
AB  - This paper presents the results of an analysis using insurance data for damage
      description and risk model verification, based on data from a Danish case. The
      results show that simple, local statistics of rainfall are not able to describe
      the variation in individual cost per claim, but are, however, feasible for
      modelling the overall cost per day. The study also shows that in combining the
      insurance and regional data it is possible to establish clear relationships
      between occurrences of claims and hazard maps. In particular, the results
      indicate that with improvements to data collection and analysis, improved
      prediction of damage costs will be possible, for example based also on
      socioeconomic variables. Furthermore, the paper concludes that more collaboration
      between scientific research and insurance agencies is needed to improve
      inundation modelling and economic assessments for urban drainage designs. 

PMID- 23863439
TI  - The occurrence and fate of phenolic compounds in a coking wastewater treatment
      plant.
AB  - The occurrence of 14 phenolic compounds (PCs) was assessed in the raw, treated
      wastewater, dewatered sludge and gas samples from a coking wastewater treatment
      plant (WWTP) in China. It was found that 3-cresol was the dominant compound in
      the raw coking wastewater with a concentration of 183 mg L(-1), and that
      chlorophenols and nitrophenols were in the level of MUg L(-1). Phenol was the
      dominant compound in the gas samples, while 2,4,6-trichlorophenol predominated in
      the dewatered sludge sample. The anaerobic and aerobic tanks played key roles in
      the elimination of chlorophenols and phenols, respectively. Analysis of daily
      mass flows of PCs in WWTP showed that 89-98% of phenols and 83-89% of
      nitrophenols were biodegraded, and that 44-69% of chlorophenols were adsorbed to
      sludge, indicating that the fate of PCs was highly influenced by their
      biodegradability and physical-chemical property. 

PMID- 23863440
TI  - Use of papaya seeds as a biosorbent of methylene blue from aqueous solution.
AB  - In this study papaya seeds were used to remove methylene blue dye from aqueous
      solution. Papaya seeds were characterized as possessing a macro/mesoporous
      texture and large pore size. Studies were carried out in batches to evaluate the
      effect of contact time and pH (2-12) on the removal of dye. It was observed that
      the adsorption of dye was better in the basic region (pH 12). The equilibrium
      data were analyzed using Langmuir, Freundlich, Dubinin-Raduschkevich, Tempkin,
      Jovanovich, Redlich-Peterson, Sips, Toth and Radke-Prausnitz isotherms. The
      equilibrium data were best described by the Langmuir isotherm with a maximum
      adsorption capacity of 637.29 mg g(-1). Adsorption kinetic data were fitted using
      the pseudo-first-order and pseudo-second-order model. The adsorption kinetic is
      very fast and was best described by the pseudo-second-order model. 

PMID- 23863441
TI  - Perspectives on modelling micropollutants in wastewater treatment plants.
AB  - Models for predicting the fate of micropollutants (MPs) in wastewater treatment
      plants (WWTPs) have been developed to provide engineers and decision-makers with
      tools that they can use to improve their understanding of, and evaluate how to
      optimize, the removal of MPs and determine their impact on the receiving waters.
      This paper provides an overview of such models, and discusses the impact of
      regulation, engineering practice and research on model development. A review of
      the current status of MP models reveals that a single model cannot represent the
      wide range of MPs that are present in wastewaters today, and that it is important
      to start considering classes of MPs based on their chemical structure or
      ecotoxicological effect, rather than the individual molecules. This paper
      identifies potential future research areas that comprise (i) considering
      transformation products in MP removal analysis, (ii) addressing advancements in
      WWTP treatment technologies, (iii) making use of common approaches to data
      acquisition for model calibration and (iv) integrating ecotoxicological effects
      of MPs in receiving waters. 

PMID- 23863442
TI  - Accuracy of different sensors for the estimation of pollutant concentrations
      (total suspended solids, total and dissolved chemical oxygen demand) in
      wastewater and stormwater.
AB  - Many field investigations have used continuous sensors (turbidimeters and/or
      ultraviolet (UV)-visible spectrophotometers) to estimate with a short time step
      pollutant concentrations in sewer systems. Few, if any, publications compare the
      performance of various sensors for the same set of samples. Different surrogate
      sensors (turbidity sensors, UV-visible spectrophotometer, pH meter, conductivity
      meter and microwave sensor) were tested to link concentrations of total suspended
      solids (TSS), total and dissolved chemical oxygen demand (COD), and sensors'
      outputs. In the combined sewer at the inlet of a wastewater treatment plant, 94
      samples were collected during dry weather, 44 samples were collected during wet
      weather, and 165 samples were collected under both dry and wet weather
      conditions. From these samples, triplicate standard laboratory analyses were
      performed and corresponding sensors outputs were recorded. Two outlier detection
      methods were developed, based, respectively, on the Mahalanobis and Euclidean
      distances. Several hundred regression models were tested, and the best ones
      (according to the root mean square error criterion) are presented in order of
      decreasing performance. No sensor appears as the best one for all three
      investigated pollutants. 

PMID- 23863443
TI  - Comparison of short-term rainfall forecasts for model-based flow prediction in
      urban drainage systems.
AB  - Forecast-based flow prediction in drainage systems can be used to implement real
      time control of drainage systems. This study compares two different types of
      rainfall forecast - a radar rainfall extrapolation-based nowcast model and a
      numerical weather prediction model. The models are applied as input to an urban
      runoff model predicting the inlet flow to a waste water treatment plant. The
      modelled flows are auto-calibrated against real-time flow observations in order
      to certify the best possible forecast. Results show that it is possible to
      forecast flows with a lead time of 24 h. The best performance of the system is
      found using the radar nowcast for the short lead times and the weather model for
      larger lead times. 

PMID- 23863444
TI  - Field-scale application of spent sulfidic caustic as a source of alternative
      electron donor for autotrophic denitrification.
AB  - Biological reuse of spent sulfidic caustic (SSC) originating from oil refineries
      is a promising method for the petrochemical industry because of low handling
      cost. SSC typically contains high concentrations of sulfur, with the most
      dominant sulfur compounds being sulfide (S(2-)). SSC is also characterized by a
      high pH and elevated alkalinity up to 5-15% by weight. Because of these
      characteristics, SSC can be used for denitrification of NO3(-)-N in the
      biological nitrogen removal process as both the electron donor and buffering
      agent in sulfur-utilizing autotrophic denitrification. In this study, two kinds
      of SSC (SSC I, SSC II) produced from two petrochemical companies were used for
      autotrophic denitrification in a field-scale wastewater treatment plant (WWTP).
      The effluent total nitrogen (TN) concentration in this process was about 10.5
      mg/L without any external carbon sources and the nitrification efficiency was
      low, about 93.0%, because of alkalinity deficiency in the influent. The injection
      of SSC I, but not SSC II, promoted nitrification efficiency, which was attributed
      to the difference in the NaOH/S ratio between SSC I and II. SSC was injected
      based on sulfide concentration of SSC required to denitrify NO3(-)-N in the WWTP.
      SSC I had higher NaOH/S than SSC II and thus could supply more alkalinity for
      nitrification than SSC II. On the other hand, additional TN removal of about 9.0%
      was achieved with the injection of both SSCs. However, denitrification efficiency
      was not proportionally increased with increasing SSC injection because of NO3(-)
      N deficiency in the anoxic tank due to the limited capacity of the recycling
      pump. For the same reason, sulfate concentration, which is the end product of
      sulfur-utilizing autotrophic denitrificaiton in the effluent, was also not
      increased with increasing SSC injection. 

PMID- 23863445
TI  - Partitioning of heavy metals in sub-surface flow treatment wetlands receiving
      high-strength wastewater.
AB  - The retention of heavy metals at two pilot-scale treatment wetlands (TWs),
      consisting of two vertical flow beds (VSSF) followed by a horizontal flow bed
      (HSSF) was studied. The TWs received high-strength wastewater: reject waters from
      sewage sludge centrifugation (RW) and landfill leachate (LL). The concentrations
      of the metals Fe, Mn, Zn, Al, Pb, Cu, Cd, Co, and Ni were measured in treated
      wastewater, substrate of the beds and in plant material harvested from the beds
      (separately in above ground (ABG) parts and below ground (BG) parts). The TWs
      differed in metals retention. In the RW treating TW the metal removal
      efficiencies varied from 27% for Pb to over 97% for Fe and Al. In the LL treating
      system the concentrations of most metals decreased after VSSF-1 and VSSF-2 beds;
      however, in the outflow from the last (HSSF) bed, the concentrations of metals
      (apart from Al) increased again, probably due to the anaerobic conditions at the
      bed. A major removal pathway was sedimentation and adsorption onto soil substrate
      as well as precipitation and co-precipitation. In the LL treating facility the
      plants contained substantially higher metal concentrations in BG parts, while the
      upward movement of metals was restricted. In the RW treating facility the BG/ABG
      ratios were lower, indicating that metals were transported to shoots. 

PMID- 23863446
TI  - Electricity production from molasses wastewater in two-chamber microbial fuel
      cell.
AB  - Molasses wastewater contains large amounts of glucose, and it can provide enough
      energy for microbial decomposition. The microbial fuel cell (MFC) in this study
      was demonstrated to be able to treat real wastewater with the benefit of
      harvesting electricity energy. Efficient operation of this MFC requires a
      molasses wastewater and preferably an inexpensive anode electrolyte. The results
      from a batch of experiments showed that molasses wastewater could not only serve
      as the electron acceptor in anode, but also generate electricity stably. A
      maximum voltage output of 514.5 mV and a maximum power density of 65.82 mW/m(2)
      were recorded at external resistance of 1,000 Omega. The MFC not only effectively
      dealt with the molasses wastewater, the chemical oxygen demand removal rate is
      81.22%, but also had a significant effect in the processing of analog silver
      wastewater. At the end of the experiment, after disassembling the device, silver
      precipitation was found stacked on the cathode carbon paper electrode, and some
      black sediment was found at the side of the proton membrane anode. 

PMID- 23863447
TI  - Virulence profile: Yoshikazu Nishikawa.

PMID- 23863448
TI  - Polymeric micelles for enhanced lymphatic drug delivery to treat metastatic
      tumors.
AB  - Polymeric micelles have been proven to be a promising nano-sized system for drug
      delivery. Understanding its in vivo behaviors at the whole body, tissue and
      cellular levels is critical for translating this drug delivery system into
      clinical practice. In this study, the 14.5 nm micelles made of polyethylene
      glycol-phosphatidylethanolamine (PEG-PE) for delivery of doxorubicin and
      vinorelbine were investigated. Using confocal and two-photon microscopy imaging
      of live mice or tissue sections, we observed that after systemic administration,
      the fluorescently labeled PEG-PE micelles encapsulating doxorubicin migrated
      through blood vessels in entirety into the interstitial tissue, collected by
      lymphatic vessels, and accumulated in lymph nodes. Importantly, encapsulated
      drugs such as vinorelbine (Nanovin), preferentially accumulate in lymph nodes
      when compared to the free drugs. Moreover, the in vivo bioluminescent imaging
      showed that Nanovin significantly reduced lymph node metastasis rate (P<0.05) in
      4 T1-luc2 murine breast tumor bearing mice. Finally, we observed that Nanovin
      enhanced antitumor activity against primary tumors and lung metastases while
      having low toxicity in various 4 T1 tumor models. This study suggests that PEG-PE
      micelle is a promising drug delivery system for the treatment of lymphatic
      metastases, and may also have important applications in other lymphatic system
      related diseases.

PMID- 23863449
TI  - CW/pulsed NIR irradiation of gold nanorods: effect on transdermal protein
      delivery mediated by photothermal ablation.
AB  - Transdermal delivery is a useful and attractive method for drug delivery, even
      though the stratum corneum is a major barrier of protein translocation into the
      skin. To achieve protein delivery through the stratum corneum, we first cast gold
      nanorods, acting as a heating device in response to near-infrared light
      irradiation, onto the skin surface. After applying an aqueous solution of
      ovalbumin to the skin, the skin was irradiated by near-infrared laser light.
      Irradiation of the skin using a continuous-wave laser increased the skin
      temperature resulting in an efficient translocation of ovalbumin into the skin.
      Furthermore, migration of inflammation cells and induction heat shock protein 70
      (HSP70) were observed. Irradiation of the skin using a pulsed laser caused an
      enhanced permeability of the stratum corneum without an increase in skin
      temperature, migration of inflammation cells, or HSP70 induction. This effect is
      due to the pulsed-laser irradiation increasing the temperature of a limited part
      of the skin surface. Thus, the physiological response of skin is dependent on the
      type of laser light used. It is anticipated that this phenomenon will find wide
      application in such applications as, for example, general transdermal protein
      delivery and transdermal vaccination. 

PMID- 23863450
TI  - Peptide targeted tripod macrocyclic Gd(III) chelates for cancer molecular MRI.
AB  - Rational design and develop of targeted contrast agents binding to cancer-related
      proteins will achieve more accurate cancer diagnosis and prognosis by magnetic
      resonance (MR) imaging. CREKA is a tumor-homing pentapeptide (Cys-Arg-Glu-Lys
      Ala) specifically homes to fibrin-fibronectin complexes abundantly expressed in
      tumor microenvironment. In this study, we developed and evaluated a CREKA peptide
      targeted multiplexed Gd-MR probe (CREKA-Tris-Gd(DOTA)3) for MR imaging of breast
      tumors. CREKA and azide bearing Gd(III) was attached to a maleimide-functional
      trialkyne scaffold via thiol-maleimide and azide-alkyne click chemistry,
      respectively. CREKA-Tris-Gd(DOTA)3 has a well-defined structure with a molecular
      weight of 2914 Da. The T1 relaxivity of CREKA-Tris-Gd(DOTA)3 is 8.06 mM(-1) s(-1)
      per Gd (24.18 mM(-1) s(-1) per molecule) at room temperature and 3 T.
      Fluorescence imaging showed high binding specificity of CREKA to a 4T1 breast
      tumor model in mice while it was not found for the scrambled CREKA (CERAK). The
      CREKA peptide-targeted contrast agent resulted in greater contrast enhancement
      than the corresponding CERAK agent and the commercialized contrast agent
      ProHance((r)) in tumor at a dose of 0.1 mmol Gd/kg in female athymic mice bearing
      4T1 breast carcinoma xenograft. This small molecular contrast agent was easily
      excreted from body after imaging indicated low toxicity. The targeted MRI
      contrast agent has a potential for specific cancer molecular imaging with MRI.

PMID- 23863451
TI  - Induction of angiogenesis using VEGF releasing genipin-crosslinked electrospun
      gelatin mats.
AB  - Rapid and controlled vascularization of engineered tissues remains one of the key
      limitations in tissue engineering applications. This study investigates the
      possible use of natural extracellular matrix-like scaffolds made of gelatin
      loaded with human vascular endothelial growth factor (VEGF), as a bioresorbable
      platform for long-term release and consequent angiogenic boosting. For this aim,
      gelatin was firstly electrospun and then cross-linked at two different
      concentrations (0.1% and 0.5% w/v) by using genipin, a low toxic agent, in order
      to fabricate a suitable substrate to be loaded with VEGF. Collected fibers were
      homogeneous and free of beads, the fibrous structure was retained after cross
      linking. Mechanical properties were deeply affected by the chemical treatment
      showing a different behavior, depending on the testing conditions (i.e., dry or
      wet state). VEGF release was assessed by means of ELISA assay: a cumulative
      release of about 90% (0.1% w/v) and 60% (0.5% w/v) at 28 days was measured. Both
      VEGF loaded mats induced cell viability, endothelial differentiation and showed
      chemoattractive properties when tested on human mesenchymal stromal cells
      (hMSCs). In vitro and in vivo angiogenic assays demonstrated that the VEGF loaded
      mats induced an angiogenic potential in stimulating new vessel formation similar,
      if not superior, to fresh VEGF. VEGF retains bioactive and pro-angiogenic
      potential for up to 14 days. The results demonstrated that genipin cross-linked
      electrospun gelatin mats loaded with VEGF could be part of a useful strategy to
      stimulate and induce angiogenesis in tissue engineered applications.

PMID- 23863452
TI  - The use of low molecular weight protamine chemical chimera to enhance monomeric
      insulin intestinal absorption.
AB  - Although oral delivery of insulin offers a number of unmatched advantages, it
      nevertheless is beset by the poor permeability of insulin molecules through the
      epithelial cell membranes of the intestinal mucosal layer. We previously reported
      the development of low molecular weight protamine (LMWP) as a non-toxic yet
      potent cell-penetrating peptide, of which via covalent linkage was capable of
      translocating protein cargos through the membranes of almost all cell types. It
      is therefore hypothesized that LMWP could be practically employed as a safe and
      effective tool to deliver insulin across the intestinal mucosal membrane, thereby
      augmenting its absorption through the GI tract. However, formulating 1:1
      monomeric insulin/LMWP conjugate presents a tall order of challenge, as the
      acidic insulin and basic LMWP would automatically form tight aggregates through
      electrostatic interactions. In this paper, we developed an innovative conjugation
      strategy to solve this problem, by using succinimidyl-[(N-maleimidopropionamido)
      polyethyleneglycol] ester (NHS-PEG-MAL) as an intermediate cross-linker during
      the coupling process. Both SDS-PAGE and MALDI-TOF mass spectroscopy confirmed the
      formation of a homogenous, monomeric (1:1 ratio) insulin/LMWP conjugate without
      encountering the conventional problem of substrate aggregation. Cell culture
      studies demonstrated that transport of the Insulin-PEG-LMWP conjugate across the
      intestinal mucosal monolayer was augmented by almost five-folds compared to
      native insulin. Furthermore, results from the in situ loop absorption tests in
      rats showed that systemic pharmacological bioavailability of insulin was
      significantly enhanced after its conjugation with LMWP. Overall, the presented
      chemical conjugation with LMWP could offer a reliable and safe means to improve
      the intestinal permeability of therapeutic peptides/proteins, shedding light of
      the possibility for their effective oral delivery. 

PMID- 23863453
TI  - The use of plasma-activated covalent attachment of early domains of tropoelastin
      to enhance vascular compatibility of surfaces.
AB  - All current metallic vascular prostheses, including stents, exhibit suboptimal
      biocompatibility. Improving the re-endothelialization and reducing the
      thrombogenicity of these devices would substantially improve their clinical
      efficacy. Tropoelastin (TE), the soluble precursor of elastin, mediates favorable
      endothelial cell interactions while having low thrombogenicity. Here we show that
      constructs of TE corresponding to the first 10 ("N10") and first 18 ("N18") N
      terminal domains of the molecule facilitate endothelial cell attachment and
      proliferation equivalent to the performance of full-length TE. This N-terminal
      ability contrasts with the known role of the C-terminus of TE in facilitating
      cell attachment, particularly of fibroblasts. When immobilized on a plasma
      activated coating ("PAC"), N10 and N18 retained their bioactivity and endothelial
      cell interactive properties, demonstrating attachment and proliferation
      equivalent to full-length TE. In whole blood assays, both N10 and N18 maintained
      the low thrombogenicity of PAC. Furthermore, these N-terminal constructs
      displayed far greater resistance to protease degradation by blood serine
      proteases kallikrein and thrombin than did full-length TE. When immobilized onto
      a PAC surface, these shorter constructs form a modified metal interface to
      establish a platform technology for biologically compatible, implantable
      cardiovascular devices. 

PMID- 23863454
TI  - Differential regulation of stiffness, topography, and dimension of substrates in
      rat mesenchymal stem cells.
AB  - The physiological microenvironment of the stem cell niche, including the three
      factors of stiffness, topography, and dimension, is crucial to stem cell
      proliferation and differentiation. Although a growing body of evidence is present
      to elucidate the importance of these factors individually, the interaction of the
      biophysical parameters of the factors remains insufficiently characterized,
      particularly for stem cells. To address this issue fully, we applied a micro
      fabricated polyacrylamide hydrogel substrate with two elasticities, two
      topographies, and three dimensions to systematically test proliferation,
      morphology and spreading, differentiation, and cytoskeletal re-organization of
      rat bone marrow mesenchymal stem cells (rBMSCs) on twelve cases. An isolated but
      not combinatory impact of the factors was found regarding the specific functions.
      Substrate stiffness or dimension is predominant in regulating cell proliferation
      by fostering cell growth on stiff, unevenly dimensioned substrate. Topography is
      a key factor for manipulating cell morphology and spreading via the formation of
      a large spherical shape in a pillar substrate but not in a grooved substrate.
      Although stiffness leads to osteogenic or neuronal differentiation of rBMSCs on a
      stiff or soft substrate, respectively, topography or dimension also plays a
      lesser role in directing cell differentiation. Neither an isolated effect nor a
      combinatory effect was found for actin or tubulin expression, whereas a seemingly
      combinatory effect of topography and dimension was found in manipulating vimentin
      expression. These results further the understandings of stem cell proliferation,
      morphology, and differentiation in a physiologically mimicking microenvironment. 

PMID- 23863455
TI  - Strategies in the development of vaccines to prevent infections with group A
      streptococcus.
AB  - There has long been interest and demand for the development of a vaccine to
      prevent infections caused by the Gram-positive organism group A streptococcus.
      Despite numerous efforts utilizing advanced approaches such as genomics,
      proteomics and bio-informatics, there is currently no vaccine. Here we review
      various strategies employed to achieve this goal. We also discuss the approach
      that we have pursued, a non-host reactive, conformationally constrained minimal B
      cell epitope from within the C-repeat region of M-protein, and the potential
      limitations in moving forward. 

PMID- 23863456
TI  - A retrospective review of patients with stage IB2 cervical cancer treated with
      radical radiation versus radical surgery as a primary modality.
AB  - OBJECTIVE: To review the efficacy of treatment modalities in patients with stage
      IB2 cervical cancer treated at Groote Schuur Hospital, Cape Town, South Africa.
      MATERIALS AND METHODS: This was a retrospective observational study of patients
      with stage IB2 cervical cancer treated from 1993 to 2008 with either primary
      radiotherapy, (with or without follow-on hysterectomy) or primary surgery (with
      or without adjuvant radiotherapy). Weekly cisplatin given concurrently with
      radiotherapy was used since 2003. Patient outcomes and grade 3 to grade 4
      treatment-related toxicities were recorded. RESULTS: The study included 78
      eligible patients for whom the 5-year overall survival rate was 70.8%. Overall 5
      year survival rate by treatment modality was 88% for the 25 patients in the
      surgery group and 62.5% for the 53 patients in the radiotherapy group. There was
      a marked difference in the proportion of patients in each group receiving
      additional therapy: 88% of patients in the primary surgery group had adjuvant
      radiotherapy, whereas only 5.7% of patients in the primary radiotherapy group
      went on to have a hysterectomy. Grade 3 to grade 4 toxicity was found in 13.2% of
      the radiotherapy group versus 4% of the surgery group (P = 0.4). CONCLUSION: The
      optimal primary treatment for stage IB2 cervical cancer remains unclear. Both
      types of primary treatments were found to be feasible therapeutic approaches.
      Primary surgery seems to have better survival outcomes at our institution.
      Selection bias including a larger median tumor size in the radiotherapy group and
      inadequate concurrent chemotherapy (<=3 cycles) in 58% of the patients receiving
      primary radiotherapy probably accounted for the difference in survival.Thus,
      primary concurrent chemoradiation is being increasingly used for these patients
      at our institution in an effort to decrease bimodal treatment and limit the
      potential for increased toxicity and treatment costs. Evidence from a randomized
      controlled study is needed to determine the optimal treatment for stage IB2
      cervical cancer.

PMID- 23863457
TI  - Radical formation at the gallium nitride nanowire-electrolyte interface by
      photoactivated charge transfer.
AB  - We investigated the transfer of photogenerated charge carriers from GaN nanowires
      into a surrounding electrolyte by electron paramagnetic resonance (EPR) and
      fluorescence spectroscopy. Using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a
      spin trap we find that the formation of hydroxyl radicals dominates in acidic,
      neutral and moderately basic environments, while in an electrolyte with a pH of
      13.5 the superoxide formation becomes detectable. We explain the two processes
      considering the redox potentials for radical formation in the electrolyte as well
      as the positions of the conduction and valence bands. The role of surface band
      bending and surface states in the semiconductor is discussed. 

PMID- 23863458
TI  - Chemoreduction improves eye retention in patients with retinoblastoma: a report
      from the German Retinoblastoma Reference Centre.
AB  - BACKGROUND: Retinoblastoma is the most common intraocular childhood tumour.
      Although mortality is low in Western countries, long-term sequelae, including
      secondary tumours, compromised vision or loss of one or both eyes are common.
      Chemoreduction combined with focal treatment is currently the leading
      conservative treatment for retinoblastoma, with success rates of 50-75% reported.
      We assessed a new chemoreduction protocol using intravenous cyclophosphamide with
      reduced dose of carboplatin on eye retention in patients with retinoblastoma.
      PROCEDURE: The 40 patients with retinoblastomas in 56 eyes were treated between
      1995 and 2004 at the German Retinoblastoma Reference Centre Essen. The 6-cycle
      chemotherapy used vincristine (days 1, 22, 43, 64, 85, 106), etoposide (days 22,
      43, 85, 106), carboplatin (days 1, 43, 64, 106), and cyclophosphamide (days 1,
      22, 64, 85). Mean follow-up was 101 months. Most patients received additional
      hyperthermia, some received local treatment with laser coagulation, cryotherapy
      and/or beta-ray brachytherapy. Therapy failure was defined as progression
      requiring enucleation or external beam radiotherapy (EBRT). RESULTS: Primary
      chemotherapy was successful in 42 of 56 eyes (75%). Therapy success and visual
      acuity at age 6 years correlated with the International Classification of
      Retinoblastoma (ICRB) group. Age at diagnosis (> or <6 months) correlated with
      relapse, but not with therapy failure or visual acuity at 6 years of age. ICRB
      group did not correlate with occurrence of relapse. CONCLUSIONS: In this
      retrospective single-centre study, chemoreduction, including cyclophosphamide,
      with or without focal treatment, effectively controlled retinoblastoma
      progression without requiring enucleation or EBRT. Addition of cyclophosphamide
      is safe, and allows reduction of carboplatin.

PMID- 23863459
TI  - Micro-dystrophin and follistatin co-delivery restores muscle function in aged DMD
      model.
AB  - Pharmacologic strategies have provided modest improvement in the devastating
      muscle-wasting disease, Duchenne muscular dystrophy (DMD). Pre-clinical gene
      therapy studies have shown promise in the mdx mouse model; however, studies
      conducted after disease onset fall short of fully correcting muscle strength or
      protecting against contraction-induced injury. Here we examine the treatment
      effect on muscle physiology in aged dystrophic mice with significant disease
      pathology by combining two promising therapies: micro-dystrophin gene replacement
      and muscle enhancement with follistatin, a potent myostatin inhibitor. Individual
      treatments with micro-dystrophin and follistatin demonstrated marked improvement
      in mdx mice but were insufficient to fully restore muscle strength and response
      to injury to wild-type levels. Strikingly, when combined, micro
      dystrophin/follistatin treatment restored force generation and conferred
      resistance to contraction-induced injury in aged mdx mice. Pre-clinical studies
      with miniature dystrophins have failed to demonstrate full correction of the
      physiological defects seen in mdx mice. Importantly, the addition of a muscle
      enhancement strategy with delivery of follistatin in combination with micro
      dystrophin gene therapy completely restored resistance to eccentric contraction
      induced injury and improved force. Eccentric contraction-induced injury is a pre
      clinical parameter relevant to the exercise induced injury that occurs in DMD
      patients, and herein, we demonstrate compelling evidence for the therapeutic
      potential of micro-dystrophin/follistatin combinatorial therapy. 

PMID- 23863461
TI  - SCG10 promotes non-amyloidogenic processing of amyloid precursor protein by
      facilitating its trafficking to the cell surface.
AB  - The processing of amyloid precursor protein (APP) is a key event in the
      pathogenesis of Alzheimer's disease. As certain cleavage pathways tend to occur
      in particular subcellular compartments, the processing of APP is greatly
      influenced by factors that regulate its trafficking. Here we report that SCG10
      directly interacts with the KFFEQ motif of the APP intracellular domain and
      promotes the non-amyloidogenic processing of the APP. Knockdown of SCG10 led to
      decreases in alpha cleavage products, sAPPalpha and CTFalpha, while increases of
      both Abeta1-40 and Abeta1-42. Elevation of SCG10 induced APP accumulation in post
      Golgi vesicles and on the cell surface by facilitating its secretory pathway. In
      addition, the APP processing was dependent on the palmitoylation-mediated
      membrane-anchoring of SCG10. Furthermore, elevation of SCG10 reduced Abeta
      accumulation and amyloid plaque formation in the hippocampus of APPswe/PS1dE9
      mice. Taken together, these results show that SCG10 has a potential role in
      preventing and treating Alzheimer's disease. 

PMID- 23863460
TI  - Hyperactive Ras/MAPK signaling is critical for tibial nonunion fracture in
      neurofibromin-deficient mice.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic disorder affecting 1 in 3500
      individuals. Patients with NF1 are predisposed to debilitating skeletal
      manifestations, including osteopenia/osteoporosis and long bone pseudarthrosis
      (nonunion fracture). Hyperactivation of the Ras/mitogen-activated protein kinase
      (MAPK) pathway in NF1 is known to underlie aberrant proliferation and
      differentiation in cell lineages, including osteoclast progenitors and
      mesenchymal stem cells (MSCs) also known as osteoblast progenitors (pro-OBLs).
      Our current study demonstrates the hyper Ras/MAPK as a critical pathway
      underlying the pathogenesis of NF1-associated fracture repair deficits. Nf1
      deficient pro-OBLs exhibit Ras/MAPK hyperactivation. Introduction of the NF1
      GTPase activating-related domain (NF1 GAP-related domain) in vitro is sufficient
      to rescue hyper Ras activity and enhance osteoblast (OBL) differentiation in Nf1(
      /-) pro-OBLs and NF1 human (h) MSCs cultured from NF1 patients with skeletal
      abnormalities, including pseudarthrosis or scoliosis. Pharmacologic inhibition of
      mitogen-activated protein kinase kinase (MEK) signaling with PD98059 partially
      rescues aberrant Erk activation while enhancing OBL differentiation and
      expression of OBL markers, osterix and osteocalcin, in Nf1-deficient murine pro
      OBLs. Similarly, MEK inhibition enhances OBL differentiation of hMSCs. In
      addition, PD98059 rescues aberrant osteoclast maturation in Nf1 haploinsufficient
      bone marrow mononuclear cells (BMMNCs). Importantly, MEK inhibitor significantly
      improves fracture healing in an NF1 murine model, Col2.3Cre;Nf1(flox/-).
      Collectively, these data indicate the Ras/MAPK cascade as a critical pathway in
      the pathogenesis of bone loss and pseudarthrosis related to NF1 mutations. These
      studies provide evidence for targeting the MAPK pathway to improve bone mass and
      treat pseudarthrosis in NF1.

PMID- 23863462
TI  - The SNM1B/APOLLO DNA nuclease functions in resolution of replication stress and
      maintenance of common fragile site stability.
AB  - SNM1B/Apollo is a DNA nuclease that has important functions in telomere
      maintenance and repair of DNA interstrand crosslinks (ICLs) within the Fanconi
      anemia (FA) pathway. SNM1B is required for efficient localization of key repair
      proteins, such as the FA protein, FANCD2, to sites of ICL damage and functions
      epistatically to FANCD2 in cellular survival to ICLs and homology-directed
      repair. The FA pathway is also activated in response to replication fork
      stalling. Here, we sought to determine the importance of SNM1B in cellular
      responses to stalled forks in the absence of a blocking lesion, such as ICLs. We
      found that depletion of SNM1B results in hypersensitivity to aphidicolin, a DNA
      polymerase inhibitor that causes replication stress. We observed that the SNM1B
      nuclease is required for efficient localization of the DNA repair proteins,
      FANCD2 and BRCA1, to subnuclear foci upon aphidicolin treatment, thereby
      indicating SNM1B facilitates direct repair of stalled forks. Consistent with a
      role for SNM1B subsequent to recognition of the lesion, we found that SNM1B is
      dispensable for upstream events, including activation of ATR-dependent signaling
      and localization of RPA, gammaH2AX and the MRE11/RAD50/NBS1 complex to
      aphidicolin-induced foci. We determined that a major consequence of SNM1B
      depletion is a marked increase in spontaneous and aphidicolin-induced chromosomal
      gaps and breaks, including breakage at common fragile sites. Thus, this study
      provides evidence that SNM1B functions in resolving replication stress and
      preventing accumulation of genomic damage. 

PMID- 23863463
TI  - Comparison of nutritional status indicators according to feeding methods in
      patients with acute stroke.
AB  - BACKGROUND: Feeding methods for patients with acute stroke differ based on their
      ability to swallow; therefore, it is necessary to determine whether these methods
      deliver enough nourishment to these patients. Although nutrition could affect
      recovery from acute stroke, it is often overlooked. Indicators of nutritional
      status are important for the nutritional assessment of patients. PURPOSE: The
      purpose of this study was to compare changes in nutritional indicators with
      various feeding methods in patients with acute stroke. METHODS: Data on 261
      patients with acute stroke who were admitted to a stroke unit in 2010 and met the
      inclusion criteria of the study were retrospectively analyzed. For comparative
      analysis, we investigated the participants' National Institutes of Health Stroke
      Scale score, feeding methods using the Modified Gugging Swallowing Screen, and
      indicators of nutritional status, such as body mass index, pre-albumin level,
      albumin level, total lymphocyte count, and total protein level. All nutritional
      indicators were compared at the time of admission to the stroke unit and at 7
      days after admission. RESULTS: At the time of admission, indicators of
      nutritional status were within normal ranges in all feeding groups (tube,
      dysphagia, and general diet). At 7 days after admission, pre-albumin (P = 0.003),
      albumin (P = 0.001), and total protein (P = 0.000) values in the tube feeding
      group were below the normal range, and the pre-albumin value and total lymphocyte
      count were below the normal range in the dysphagia diet group (P = 0.027). The
      values for all nutritional indicators were within normal limits in the general
      diet group. CONCLUSIONS: Indicators of nutritional status change according to the
      swallowing ability of patients with acute stroke. At 7 days after admission to
      the stroke unit, patients with severe dysphagia had higher levels of indicators
      of malnutrition. Health care providers should consider whether the feeding method
      of each patient with stroke provides suitable nourishment. Additionally, it is
      important to know why these indicators vary based on swallowing abilities and
      what these patients require for adequate nutrition.

PMID- 23863464
TI  - AMP-activated protein kinase regulates the vacuolar H+-ATPase via direct
      phosphorylation of the A subunit (ATP6V1A) in the kidney.
AB  - The vacuolar H(+)-ATPase (V-ATPase) in intercalated cells contributes to luminal
      acidification in the kidney collecting duct and nonvolatile acid excretion. We
      previously showed that the A subunit in the cytoplasmic V1 sector of the V-ATPase
      (ATP6V1A) is phosphorylated by the metabolic sensor AMP-activated protein kinase
      (AMPK) in vitro and in kidney cells. Here, we demonstrate that treatment of
      rabbit isolated, perfused collecting ducts with the AMPK activator 5
      aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) inhibited V-ATPase
      dependent H(+) secretion from intercalated cells after an acid load. We have
      identified by mass spectrometry that Ser-384 is a major AMPK phosphorylation site
      in the V-ATPase A subunit, a result confirmed by comparing AMPK-dependent
      phosphate labeling of wild-type A-subunit (WT-A) with that of a Ser-384-to-Ala A
      subunit mutant (S384A-A) in vitro and in intact HEK-293 cells. Compared with WT-A
      expressing HEK-293 cells, S384A-A-expressing cells exhibited greater steady-state
      acidification of HCO3(-)-containing media. Moreover, AICAR treatment of clone C
      rabbit intercalated cells expressing the WT-A subunit reduced V-ATPase-dependent
      extracellular acidification, an effect that was blocked in cells expressing the
      phosphorylation-deficient S384A-A mutant. Finally, expression of the S384A-A
      mutant prevented cytoplasmic redistribution of the V-ATPase by AICAR in clone C
      cells. In summary, direct phosphorylation of the A subunit at Ser-384 by AMPK
      represents a novel regulatory mechanism of the V-ATPase in kidney intercalated
      cells. Regulation of the V-ATPase by AMPK may couple V-ATPase activity to
      cellular metabolic status with potential relevance to ischemic injury in the
      kidney and other tissues.

PMID- 23863465
TI  - Evidence for increased renal tubule and parathyroid gland sensitivity to serum
      calcium in human idiopathic hypercalciuria.
AB  - Patients with idiopathic hypercalciuria (IH) have decreased renal calcium
      reabsorption, most marked in the postprandial state, but the mechanisms are
      unknown. We compared 29 subjects with IH and 17 normal subjects (N) each fed
      meals providing identical amounts of calcium. Urine and blood samples were
      collected fasting and after meals. Levels of three candidate signalers, serum
      calcium (SCa), insulin (I), and plasma parathyroid hormone (PTH), did not differ
      between IH and N either fasting or fed, but all changed with feeding, and the
      change in SCa was greater in IH than in N. Regression analysis of fractional
      excretion of calcium (FECa) was significant for PTH and SCa in IH but not N. With
      the use of multivariable analysis, Sca entered the model while PTH and I did not.
      To avoid internal correlation we decomposed FECa into its independent terms:
      adjusted urine calcium (UCa) and UFCa molarity. Analyses using adjusted Uca and
      unadjusted Uca parallel those using FECa, showing a dominant effect of SCa with
      no effect of PTH or I. The effect of SCa may be mediated via vitamin D receptor
      stimulated increased abundance of basolateral Ca receptor, which is supported by
      the fact PTH levels also seem more responsive to serum Ca in IH than in N.
      Although our data support an effect of SCa on FECa and UCa, which is more marked
      in IH than in N, it can account for only a modest fraction of the meal effect,
      perhaps 10-20%, suggesting additional mediators are also responsible for the
      exaggerated postprandial hypercalciuria seen in IH. 

PMID- 23863466
TI  - An anatomically unbiased approach for analysis of renal BOLD magnetic resonance
      images.
AB  - Oxygenation defects may contribute to renal disease progression, but the
      chronology of events is difficult to define in vivo without recourse to invasive
      methodologies. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI)
      provides an attractive alternative, but the R2* signal is physiologically
      complex. Postacquisition data analysis often relies on manual selection of
      region(s) of interest. This approach excludes from analysis significant
      quantities of biological information and is subject to selection bias. We present
      a semiautomated, anatomically unbiased approach to compartmentalize voxels into
      two quantitatively related clusters. In control F344 rats, low R2* clustering was
      located predominantly within the cortex and higher R2* clustering within the
      medulla (70.96 +/- 1.48 vs. 79.00 +/- 1.50; 3 scans per rat; n = 6; P < 0.01)
      consistent anatomically with a cortico-medullary oxygen gradient. An intravenous
      bolus of acetylcholine caused a transient reduction of the R2* signal in both
      clustered segments (P < 0.01). This was nitric oxide dependent and temporally
      distinct from the hemodynamic effects of acetylcholine. Rats were then
      chronically infused with angiotensin II (60 ng/min) and rescanned 3 days later.
      Clustering demonstrated a disruption of the cortico-medullary gradient, producing
      less distinctly segmented mean R2* clusters (71.30 +/- 2.00 vs. 72.48 +/- 1.27; n
      = 6; NS). The acetylcholine-induced attenuation of the R2* signal was abolished
      by chronic angiotensin II infusion, consistent with reduced nitric oxide
      bioavailability. This global map of oxygenation, defined by clustering individual
      voxels on the basis of quantitative nearness, might be more robust in defining
      deficits in renal oxygenation than the absolute magnitude of R2* in small,
      manually selected regions of interest defined exclusively by anatomical nearness.

PMID- 23863468
TI  - Renalase regulates renal dopamine and phosphate metabolism.
AB  - Renalase is a kidney-secreted catecholamines-degrading enzyme whose expression
      and activity are downregulated by increased dietary phosphate. A renalase
      knockout (KO) mouse model was used to explore the mechanisms mediating renalase's
      effect on phosphate excretion. Compared with wild-type (WT) mice maintained on a
      regular diet, KO mice show decreased serum PO4(-) (KO = 5.3 +/- 0.2 vs. WT = 6.0
      +/- 0.1, n = 6; P < 0.04) and increased urinary PO4(-) excretion (urine PO4(
      )/creatinine: KO = 7.7 +/- 0.3 vs. WT = 6.1 +/- 0.3, n = 6; P < 0.02). However,
      both WT and KO mice respond similarly to PO4(-) restriction by increasing renal
      COMT-1 activity and markedly decreasing PO4(-) excretion, which excludes an
      intrinsic renal defect in the KO. Renal sodium-phosphate cotransporter Npt2a,
      sodium proton exchanger NHE3 expression, and MAO-A and B activity did not differ
      between WT and KO. Only catechol-O-methyl transferase (COMT) expression and
      activity were significantly increased in KO mice. Despite that, urinary dopamine
      increased by twofold, whereas urinary l-DOPA excretion decreased by twofold in
      the KO mouse, indicating an upregulation of renal dopamine (DA) synthesis. These
      data indicate that renalase deficiency is associated with increased renal DA
      synthesis, stimulated PO4(-) excretion, and moderately severe hypophosphatemia.
      The signal to increase renal DA synthesis is strong since it overcomes a
      compensatory increase in COMT activity. 

PMID- 23863467
TI  - Thrombospondin 1 mediates renal dysfunction in a mouse model of high-fat diet
      induced obesity.
AB  - Obesity is prevalent worldwide and is a major risk factor for many diseases
      including renal complications. Thrombospondin 1 (TSP1), a multifunctional
      extracellular matrix protein, plays an important role in diabetic kidney
      diseases. However, whether TSP1 plays a role in obesity-related kidney disease is
      unknown. In the present studies, the role of TSP1 in obesity-induced renal
      dysfunction was determined by using a diet-induced obese mouse model. The results
      demonstrated that TSP1 was significantly upregulated in the kidney from obese
      mice. The increased TSP1 was localized in the glomerular mesangium as well as in
      the tubular system from obese wild-type mice. Obese wild-type mice developed
      renal hypertrophy and albuminuria, which was associated with increased kidney
      macrophage infiltration, augmented kidney inflammation, and activated
      transforming growth factor (TGF)-beta signaling and renal fibrosis. In contrast,
      obese TSP1-deficient mice did not develop these kidney damages. Furthermore, in
      vitro studies demonstrated that leptin treatment stimulated the expression of
      TSP1, TGF-beta1, fibronectin, and collagen type IV in mesangial cells isolated
      from wild-type mice. These leptin-stimulated effects were abolished in TSP1
      deficient mesangial cells. Taken together, these data suggest that TSP1 is an
      important mediator for obesity- or hyperleptinemia-induced kidney dysfunction. 

PMID- 23863469
TI  - The inhibitory effect of Gbetagamma and Gbeta isoform specificity on ENaC
      activity.
AB  - Epithelial Na(+) channel (ENaC) activity, which determines the rate of renal
      Na(+) reabsorption, can be regulated by G protein-coupled receptors. Regulation
      of ENaC by Galpha-mediated downstream effectors has been studied extensively, but
      the effect of Gbetagamma dimers on ENaC is unclear. A6 cells endogenously contain
      high levels of Gbeta1 but low levels of Gbeta3, Gbeta4, and Gbeta5 were detected
      by Q-PCR. We tested Ggamma2 combined individually with Gbeta1 through Gbeta5
      expressed in A6 cells, after which we recorded single-channel ENaC activity.
      Among the five beta and gamma2 combinations, beta1gamma2 strongly inhibits ENaC
      activity by reducing both ENaC channel number (N) and open probability (Po)
      compared with control cells. In contrast, the other four beta-isoforms combined
      with gamma2 have no significant effect on ENaC activity. By using various
      inhibitors to probe Gbeta1gamma2 effects on ENaC regulation, we found that
      Gbeta1gamma2-mediated ENaC inhibition involved activation of phospholipase C-beta
      and its enzymatic products that induce protein kinase C and ERK1/2 signaling
      pathways. 

PMID- 23863471
TI  - Of diabetic mice and ACE2: a new biomarker of renal disease?

PMID- 23863470
TI  - Fulvene-5 inhibition of Nadph oxidases attenuates activation of epithelial sodium
      channels in A6 distal nephron cells.
AB  - Nadph oxidase 4 is an important cellular source of reactive oxygen species (ROS)
      generation in the kidney. Novel antioxidant drugs, such as Nox4 inhibitor
      compounds, are being developed. There is, however, very little experimental
      evidence for the biological role and regulation of Nadph oxidase isoforms in the
      kidney. Herein, we show that Fulvene-5 is an effective inhibitor of Nox-generated
      ROS and report the role of Nox isoforms in activating epithelial sodium channels
      (ENaC) in A6 distal nephron cells via oxidant signaling and cell stretch
      activation. Using single-channel patch-clamp analysis, we report that Fulvene-5
      blocked the increase in ENaC activity that is typically observed with H2O2
      treatment of A6 cells: average ENaC NPo values decreased from a baseline level of
      1.04 +/- 0.18 (means +/- SE) to 0.25 +/- 0.08 following Fulvene-5 treatment. H2O2
      treatment failed to increase ENaC activity in the presence of Fulvene-5.
      Moreover, Fulvene-5 treatment of A6 cells blocked the osmotic cell stretch
      response of A6 cells, indicating that stretch activation of Nox-derived ROS plays
      an important role in ENaC regulation. Together, these findings indicate that
      Fulvene-5, and perhaps other classes of antioxidant inhibitors, may represent a
      novel class of compounds useful for the treatment of pathological disorders
      stemming from inappropriate ion channel activity, such as hypertension.

PMID- 23863473
TI  - Sensitive detection of melanoma metastasis using circulating microRNA expression
      profiles.
AB  - Numerous studies have indicated that the serum levels of microRNAs are useful for
      the diagnosis or evaluation of activity in human diseases. However, determining
      the level of only one of the nearly 2000 microRNAs identified so far may be less
      significant. Accordingly, we examined the possibility that the expression pattern
      of multiple microRNAs in each patient may be a more reliable disease marker for
      melanoma, especially metastatic disease, focusing on the interaction among
      microRNAs. Six microRNAs (miR-9, miR-145, miR-150, miR-155, miR-203, and miR-205)
      were evaluated using real-time PCR in 11 patients with metastatic melanoma and in
      16 patients without melanoma. The expression of the six microRNAs was
      significantly different between the patients with metastasis and those without
      it. MiR-9 and miR-205 and miR-203 and miR-205 showed significant correlations,
      and the combination of miR-9, miR-145, miR-150, miR-155, and miR-205 was more
      sensitive than when each miR was used individually to distinguish the patients
      with metastasis from those without it. This is the first report demonstrating the
      expression profiles of multiple microRNAs in melanoma patients. Clarifying the
      involvement of the microRNA network in the pathogenesis of melanoma may
      contribute to the development of new diagnostic tools and to advancing the
      understanding of this disease. 

PMID- 23863475
TI  - Perspectives and industrial potential of PGA selectivity and promiscuity.
AB  - Penicillin G acylases (PGAs) are robust industrial catalysts used for
      biotransformation of beta-lactams into key intermediates for chemical production
      of semi-synthetic beta-lactam antibiotics by hydrolysis of natural penicillins.
      They are used also in reverse, kinetically controlled synthetic reactions for
      large-scale productions of these antibiotics from corresponding beta-lactam
      nuclei and activated acyl donors. Further biocatalytic applications of PGAs have
      recently been described: catalysis of peptide syntheses and the resolutions of
      racemic mixtures for the production of enantiopure active pharmaceutical
      ingredients that are based on enantioselective acylation or chiral hydrolysis.
      Moreover, PGAs rank among promiscuous enzymes because they also catalyze
      reactions such as trans-esterification, Markovnikov addition or Henry reaction.
      This particular biocatalytic versatility represents a driving force for the
      discovery of novel members of this enzyme family and further research into the
      catalytic potential of PGAs. This review deals with biocatalytic applications
      exploiting enantioselectivity and promiscuity of prokaryotic PGAs that have been
      recently reported. Biocatalytic applications are discussed and presented with
      reaction substrates converted into active compounds useful for the pharmaceutical
      industry. 

PMID- 23863474
TI  - Epispadias in boys with an intact prepuce.
AB  - OBJECTIVE: To present an overview of the clinical presentation and pathological
      anatomy, and the results of surgical correction of 7 cases of epispadias with
      intact prepuce; a rare condition that has only occasionally been reported in
      literature. PATIENTS AND METHODS: A retrospective search was performed in the
      surgical and diagnoses database between 1991 and 2011. Seven cases of epispadias
      with intact prepuce were identified. Five presented as a webbed and buried penis,
      1 as phimosis and 1 with suspicion for congenital anomaly of the genitalia.
      RESULTS: In 3 of 7 cases, epispadias was suspected or diagnosed at first
      presentation and could be surgically corrected in the first intervention. In the
      other 4 cases, epispadias was discovered during surgery, requiring an additional
      intervention to perform epispadias repair in 3 cases. One boy was diagnosed with
      glandular, 3 with coronal, 1 with shaft and 2 with penopubic epispadias.
      Epispadias repair was successful with regard to cosmesis and erectile function.
      Five patients developed normal continence after surgery, 1 after intensive
      urotherapy. An under average penile length was the main reported problem during
      follow-up. CONCLUSION: In the diagnostic process for a concealed penis, the
      possibility of epispadias should be considered. If epispadias is suspected or
      confirmed, epispadias repair can occur in the first intervention, reducing the
      number of additional interventions. Epispadias with intact prepuce appears to
      have a better prognosis concerning urinary continence compared to classical
      epispadias.

PMID- 23863472
TI  - Novel diuretic targets.
AB  - As the molecular revolution continues to inform a deeper understanding of disease
      mechanisms and pathways, there exist unprecedented opportunities for translating
      discoveries at the bench into novel therapies for improving human health. Despite
      the availability of several different classes of antihypertensive medications,
      only about half of the 67 million Americans with hypertension manage their blood
      pressure appropriately. A broader selection of structurally diverse
      antihypertensive drugs acting through different mechanisms would provide
      clinicians with greater flexibility in developing effective treatment regimens
      for an increasingly diverse and aging patient population. An emerging body of
      physiological, genetic, and pharmacological evidence has implicated several renal
      ion-transport proteins, or regulators thereof, as novel, yet clinically
      unexploited, diuretic targets. These include the renal outer medullary potassium
      channel, ROMK (Kir1.1), Kir4.1/5.1 potassium channels, ClC-Ka/b chloride
      channels, UTA/B urea transporters, the chloride/bicarbonate exchanger pendrin,
      and the STE20/SPS1-related proline/alanine-rich kinase (SPAK). The molecular
      pharmacology of these putative targets is poorly developed or lacking altogether;
      however, recent efforts by a few academic and pharmaceutical laboratories have
      begun to lessen this critical barrier. Here, we review the evidence in support of
      the aforementioned proteins as novel diuretic targets and highlight examples
      where progress toward developing small-molecule pharmacology has been made.

PMID- 23863476
TI  - Oxytonergic circuitry sustains and enables creative cognition in humans.
AB  - Creativity enables humans to adapt flexibly to changing circumstances, to manage
      complex social relations and to survive and prosper through social, technological
      and medical innovations. In humans, chronic, trait-based as well as temporary,
      state-based approach orientation has been linked to increased capacity for
      divergent rather than convergent thinking, to more global and holistic processing
      styles and to more original ideation and creative problem solving. Here, we link
      creative cognition to oxytocin, a hypothalamic neuropeptide known to up-regulate
      approach orientation in both animals and humans. Study 1 (N = 492) showed that
      plasma oxytocin predicts novelty-seeking temperament. Study 2 (N = 110) revealed
      that genotype differences in a polymorphism in the oxytocin receptor gene
      rs1042778 predicted creative ideation, with GG/GT-carriers being more original
      than TT-carriers. Using double-blind placebo-controlled between-subjects designs,
      Studies 3-6 (N = 191) finally showed that intranasal oxytocin (vs matching
      placebo) reduced analytical reasoning, and increased holistic processing,
      divergent thinking and creative performance. We conclude that the oxytonergic
      circuitry sustains and enables the day-to-day creativity humans need for survival
      and prosperity and discuss implications. 

PMID- 23863477
TI  - beta1 integrin is a crucial regulator of pancreatic beta-cell expansion.
AB  - Development of the endocrine compartment of the pancreas, as represented by the
      islets of Langerhans, occurs through a series of highly regulated events
      encompassing branching of the pancreatic epithelium, delamination and
      differentiation of islet progenitors from ductal domains, followed by expansion
      and three-dimensional organization into islet clusters. Cellular interactions
      with the extracellular matrix (ECM) mediated by receptors of the integrin family
      are postulated to regulate key functions in these processes. Yet, specific events
      regulated by these receptors in the developing pancreas remain unknown. Here, we
      show that ablation of the beta1 integrin gene in developing pancreatic beta-cells
      reduces their ability to expand during embryonic life, during the first week of
      postnatal life, and thereafter. Mice lacking beta1 integrin in insulin-producing
      cells exhibit a dramatic reduction of the number of beta-cells to only ~18% of
      wild-type levels. Despite the significant reduction in beta-cell mass, these
      mutant mice are not diabetic. A thorough phenotypic analysis of beta-cells
      lacking beta1 integrin revealed a normal expression repertoire of beta-cell
      markers, normal architectural organization within islet clusters, and a normal
      ultrastructure. Global gene expression analysis revealed that ablation of this
      ECM receptor in beta-cells inhibits the expression of genes regulating cell cycle
      progression. Collectively, our results demonstrate that beta1 integrin receptors
      function as crucial positive regulators of beta-cell expansion. 

PMID- 23863478
TI  - Specification of dopaminergic subsets involves interplay of En1 and Pitx3.
AB  - Mesodiencephalic dopaminergic (mdDA) neurons control locomotion and emotion and
      are affected in multiple psychiatric and neurodegenerative diseases, including
      Parkinson's disease (PD). The homeodomain transcription factor Pitx3 is pivotal
      in mdDA neuron development and loss of Pitx3 results in programming deficits in a
      rostrolateral subpopulation of mdDA neurons destined to form the substantia nigra
      pars compacta (SNc), reminiscent of the specific cell loss observed in PD. We
      show here that in adult mice in which the gene encoding a second homeoprotein,
      engrailed 1 (En1), has been deleted, dramatic loss of mdDA neurons and striatal
      innervation defects were observed, partially reminiscent of defects observed in
      Pitx3(-/-) mice. We then continue to reveal developmental crosstalk between En1
      and Pitx3 through genome-wide expression analysis. During development, both En1
      and Pitx3 are required to induce expression of mdDA genes in the rostrolateral
      subset destined to form the SNc. By contrast, Pitx3 and En1 reciprocally regulate
      a separate gene cluster, which includes Cck, demarcating a caudal mdDA subset in
      wild-type embryos. Whereas En1 is crucial for induction of this caudal phenotype,
      Pitx3 antagonizes it rostrolaterally. The combinatorial action of En1 and Pitx3
      is potentially realized through at least three levels of molecular interaction:
      (1) influencing each other's expression level, (2) releasing histone deacetylase
      mediated repression of Nurr1 target genes and (3) modulating En1 activity through
      Pitx3-driven activation of En1 modulatory proteins. These findings show how two
      crucial mediators of mdDA neuronal development, En1 and Pitx3, interact in
      dopaminergic subset specification, the importance of which is exemplified by the
      specific vulnerability of the SNc found in PD. 

PMID- 23863479
TI  - Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting
      Yap/Taz transcriptional coactivators.
AB  - Brain development requires a precise balance between expansion of the neural
      progenitor pool and the production of postmitotic neurons and glia. Disruption of
      this equilibrium results in a myriad of structural abnormalities and disorders of
      the nervous system. The molecular mechanism that restricts neural progenitor
      expansion is poorly understood. Here we show that the tumor suppressor
      neurofibromatosis 2 (Nf2; merlin) limits the expansion of neural progenitor cells
      (NPCs) in the mammalian dorsal telencephalon. Nf2 is localized at the apical
      region of NPCs. In the absence of Nf2, NPCs of the cortical hem, hippocampal
      primordium and neocortical primordium overexpand, while production of Cajal
      Retzius cells and hippocampal neurons decreases, resulting in severe malformation
      of the hippocampus in adult mice. We further show that Nf2 functions by
      inhibiting the Yap/Taz transcriptional coactivators, probably through a mechanism
      that is distinct from the canonical Hippo pathway. Overexpressing human YAP in
      NPCs causes a hippocampal malformation phenotype that closely resembles that of
      Nf2 mutants and, importantly, deleting Yap in the Nf2 mutant background largely
      restores hippocampal development. Our studies uncover Nf2 as an important
      inhibitor of neural progenitor expansion and establish Yap/Taz as key downstream
      effectors of Nf2 during brain development. 

PMID- 23863480
TI  - Circulating Bmp10 acts through endothelial Alk1 to mediate flow-dependent
      arterial quiescence.
AB  - Blood flow plays crucial roles in vascular development, remodeling and
      homeostasis, but the molecular pathways required for transducing flow signals are
      not well understood. In zebrafish embryos, arterial expression of activin
      receptor-like kinase 1 (alk1), which encodes a TGFbeta family type I receptor, is
      dependent on blood flow, and loss of alk1 mimics lack of blood flow in terms of
      dysregulation of a subset of flow-responsive arterial genes and increased
      arterial endothelial cell number. These data suggest that blood flow activates
      Alk1 signaling to promote a flow-responsive gene expression program that limits
      nascent arterial caliber. Here, we demonstrate that restoration of endothelial
      alk1 expression to flow-deprived arteries fails to rescue Alk1 activity or
      normalize arterial endothelial cell gene expression or number, implying that
      blood flow may play an additional role in Alk1 signaling independent of alk1
      induction. To this end, we define cardiac-derived Bmp10 as the crucial ligand for
      endothelial Alk1 in embryonic vascular development, and provide evidence that
      circulating Bmp10 acts through endothelial Alk1 to limit endothelial cell number
      in and thereby stabilize the caliber of nascent arteries. Thus, blood flow
      promotes Alk1 activity by concomitantly inducing alk1 expression and distributing
      Bmp10, thereby reinforcing this signaling pathway, which functions to limit
      arterial caliber at the onset of flow. Because mutations in ALK1 cause
      arteriovenous malformations (AVMs), our findings suggest that an impaired flow
      response initiates AVM development. 

PMID- 23863481
TI  - Bmp signaling represses Vegfa to promote outflow tract cushion development.
AB  - Congenital heart disease (CHD) is a devastating anomaly that affects ~1% of live
      births. Defects of the outflow tract (OFT) make up a large percentage of human
      CHD. We investigated Bmp signaling in mouse OFT development by conditionally
      deleting both Bmp4 and Bmp7 in the second heart field (SHF). SHF Bmp4/7
      deficiency resulted in defective epithelial to mesenchymal transition (EMT) and
      reduced cardiac neural crest ingress, with resultant persistent truncus
      arteriosus. Using a candidate gene approach, we found that Vegfa was upregulated
      in the Bmp4/7 mutant hearts. To determine if Vegfa is a downstream Bmp effector
      during EMT, we examined whether Vegfa is transcriptionally regulated by the Bmp
      receptor-regulated Smad. Our findings indicate that Smad directly binds to Vegfa
      chromatin and represses Vegfa transcriptional activity. We also found that Vegfa
      is a direct target for the miR-17-92 cluster, which is also regulated by Bmp
      signaling in the SHF. Deletion of miR-17-92 reveals similar phenotypes to Bmp4/7
      SHF deletion. To directly address the function of Vegfa repression in Bmp
      mediated EMT, we performed ex vivo explant cultures from Bmp4/7 and miR-17-92
      mutant hearts. EMT was defective in explants from the Bmp4/7 double conditional
      knockout (dCKO; Mef2c-Cre;Bmp4/7(f/f)) and miR-17-92 null. By antagonizing Vegfa
      activity in explants, EMT was rescued in Bmp4/7 dCKO and miR-17-92 null culture.
      Moreover, overexpression of miR-17-92 partially suppressed the EMT defect in
      Bmp4/7 mutant embryos. Our study reveals that Vegfa levels in the OFT are tightly
      controlled by Smad- and microRNA-dependent pathways to modulate OFT development. 

PMID- 23863482
TI  - Inactivation of LAR family phosphatase genes Ptprs and Ptprf causes craniofacial
      malformations resembling Pierre-Robin sequence.
AB  - Leukocyte antigen related (LAR) family receptor protein tyrosine phosphatases
      (RPTPs) regulate the fine balance between tyrosine phosphorylation and
      dephosphorylation that is crucial for cell signaling during development and
      tissue homeostasis. Here we show that LAR RPTPs are required for normal
      development of the mandibular and maxillary regions. Approximately half of the
      mouse embryos lacking both Ptprs (RPTPsigma) and Ptprf (LAR) exhibit micrognathia
      (small lower jaw), cleft palate and microglossia/glossoptosis (small and deep
      tongue), a phenotype closely resembling Pierre-Robin sequence in humans. We show
      that jaw bone and cartilage patterning occurs aberrantly in LAR family
      phosphatase-deficient embryos and that the mandibular arch harbors a marked
      decrease in cell proliferation. Analysis of signal transduction in embryonic
      tissues and mouse embryonic fibroblast cultures identifies an increase in Bmp
      Smad signaling and an abrogation of canonical Wnt signaling associated with loss
      of the LAR family phosphatases. A reactivation of beta-catenin signaling by
      chemical inhibition of GSK3beta successfully resensitizes LAR family phosphatase
      deficient cells to Wnt induction, indicating that RPTPs are necessary for normal
      Wnt/beta-catenin pathway activation. Together these results identify LAR RPTPs as
      important regulators of craniofacial morphogenesis and provide insight into the
      etiology of Pierre-Robin sequence. 

PMID- 23863483
TI  - MRAS GTPase is a novel stemness marker that impacts mouse embryonic stem cell
      plasticity and Xenopus embryonic cell fate.
AB  - Pluripotent mouse embryonic stem cells (mESCs), maintained in the presence of the
      leukemia inhibitory factor (LIF) cytokine, provide a powerful model with which to
      study pluripotency and differentiation programs. Extensive microarray studies on
      cultured cells have led to the identification of three LIF signatures. Here we
      focus on muscle ras oncogene homolog (MRAS), which is a small GTPase of the Ras
      family encoded within the Pluri gene cluster. To characterise the effects of Mras
      on cell pluripotency and differentiation, we used gain- and loss-of-function
      strategies in mESCs and in the Xenopus laevis embryo, in which Mras gene
      structure and protein sequence are conserved. We show that persistent knockdown
      of Mras in mESCs reduces expression of specific master genes and that MRAS plays
      a crucial role in the downregulation of OCT4 and NANOG protein levels upon
      differentiation. In Xenopus, we demonstrate the potential of Mras to modulate
      cell fate at early steps of development and during neurogenesis. Overexpression
      of Mras allows gastrula cells to retain responsiveness to fibroblast growth
      factor (FGF) and activin. Collectively, these results highlight novel conserved
      and pleiotropic effects of MRAS in stem cells and early steps of development. 

PMID- 23863484
TI  - Notch3 signaling gates cell cycle entry and limits neural stem cell amplification
      in the adult pallium.
AB  - Maintaining the homeostasis of germinal zones in adult organs is a fundamental
      but mechanistically poorly understood process. In particular, what controls stem
      cell activation remains unclear. We have previously shown that Notch signaling
      limits neural stem cell (NSC) proliferation in the adult zebrafish pallium.
      Combining pharmacological and genetic manipulations, we demonstrate here that
      long-term Notch invalidation primarily induces NSC amplification through their
      activation from quiescence and increased occurrence of symmetric divisions.
      Expression analyses, morpholino-mediated invalidation and the generation of a
      notch3-null mutant directly implicate Notch3 in these effects. By contrast,
      abrogation of notch1b function results in the generation of neurons at the
      expense of the activated NSC state. Together, our results support a differential
      involvement of Notch receptors along the successive steps of NSC recruitment.
      They implicate Notch3 at the top of this hierarchy to gate NSC activation and
      amplification, protecting the homeostasis of adult NSC reservoirs under
      physiological conditions. 

PMID- 23863485
TI  - Gene transcription is coordinated with, but not dependent on, cell divisions
      during C. elegans embryonic fate specification.
AB  - Cell differentiation and proliferation are coordinated during animal development,
      but the link between them remains uncharacterized. To examine this relationship,
      we combined single-molecule RNA imaging with time-lapse microscopy to generate
      high-resolution measurements of transcriptional dynamics in Caenorhabditis
      elegans embryogenesis. We found that globally slowing the overall development
      rate of the embryo by altering temperature or by mutation resulted in cell
      proliferation and transcription slowing, but maintaining, their relative timings,
      suggesting that cell division may directly control transcription. However, using
      mutants with specific defects in cell cycle pathways that lead to abnormal
      lineages, we found that the order between cell divisions and expression onset can
      switch, showing that expression of developmental regulators is not strictly
      dependent on cell division. Delaying cell divisions resulted in only slight
      changes in absolute expression time, suggesting that expression and proliferation
      are independently entrained to a separate clock-like process. These changes in
      relative timing can change the number of cells expressing a gene at a given time,
      suggesting that timing may help determine which cells adopt particular
      transcriptional patterns. Our results place limits on the types of mechanisms
      that are used during normal development to ensure that division timing and fate
      specification occur at appropriate times. 

PMID- 23863487
TI  - The return to the USA of doxylamine-pyridoxine delayed release combination
      (Diclegis(r)) for morning sickness--a new morning for American women.
AB  - The US FDA approval in April 2013 of Diclegis(r), the doxylamine-pyridoxine
      combination for morning sickness, is a major milestone, particularly since it is
      indicated for use in pregnancy and the FDA has labeled it a pregnancy category A
      drug the strongest evidence of fetal safety. After thirty years of being orphaned
      from an FDA-labeled drug for the most common medical condition in pregnancy,
      American women and their health care providers have a therapeutic solution that
      is likely to positively impact millions of women each year. This review
      highlights the milestones of this antiemetic agent over the last 40 years.

PMID- 23863488
TI  - Selective cerebral perfusion with aortic cannulation and short-term hypothermic
      circulatory arrest in aortic arch reconstruction.
AB  - BACKGROUND: The deep hypothermic circulatory arrest (DHCA) technique has been
      used in aortic arch and isthmus hypoplasia for many years. However, with the
      demonstration of the deleterious effects of prolonged DHCA, selective cerebral
      perfusion (SCP) has started to be used in aortic arch repair. For SCP, perfusion
      via the innominate artery route is generally preferred (either direct innominate
      artery cannulation or re-routing of the cannula in the aorta is used). Herein, we
      describe our technique and the result of arch reconstruction in combination with
      selective cerebral and myocardial perfusion (SCMP) and short-term total
      circulatory arrest (TCA) (5-10 min) through ascending aortic cannulation.
      METHODS: Thirty-seven cases with aortic arch and isthmus hypoplasia accompanying
      cardiac defects were operated on with SCMP and short TCA in Baskent University
      Istanbul Research and Training Hospital between January 2007 and Sep 2012. There
      were 17 cases with ventricular septal defect (VSD)-coarctation with aortic arch
      hypoplasia (CoAAH), 4 cases of transposition of the great arteries-VSD-CoAAH, 4
      cases of Taussing Bing Anomaly-CoAAH, 2 cases complete atrioventricular canal
      defect-CoAAH, 3 cases single ventricle-CoAAH, 3 cases of type A interruption-VSD,
      2 subvalvular aortic stenosis-CoAAH and 2 cases of isolated CoAAH. The aorta was
      cannulated in the middle of the ascending aorta in all cases. The cross-clamp was
      applied to the aortic arch distal to either the innominate artery or the left
      carotid artery. In addition, a side-biting clamp was applied to the descending
      aorta. The aorta between these two clamps was reconstructed with gluteraldehyde
      treated autogeneous pericardium, using SCMP. The proximal arch and distal
      ascending aorta reconstructions were carried out under short TCA. RESULTS: The
      mean age of the patients was 2.5 +/- 2 months. The mean cardiopulmonary bypass
      and cross-clamp times were 144 +/- 58 and 43 +/- 27 minutes, respectively. The
      mean SCMP and descending aorta ischemia times were 22.6 +/- 4.8 and 27 +/- 6.3
      minutes, respectively. Mean TCA time was 7.6 +/- 2.1 minutes (min: 4, max 10
      min). The mean in-hospital stay time was 8.6 +/- 1.9 days. None of the cases
      operated with this technique had neurological defects. The mortality rate was
      2.7% (1 patient). CONCLUSION: SCMP with aortic cannulation and short TCA (under
      10 minutes) in aortic reconstruction is safe and practical in this high-risk
      patient group.

PMID- 23863486
TI  - The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast
      differentiation.
AB  - The mouse incisor is a remarkable tooth that grows throughout the animal's
      lifetime. This continuous renewal is fueled by adult epithelial stem cells that
      give rise to ameloblasts, which generate enamel, and little is known about the
      function of microRNAs in this process. Here, we describe the role of a novel
      Pitx2:miR-200c/141:noggin regulatory pathway in dental epithelial cell
      differentiation. miR-200c repressed noggin, an antagonist of Bmp signaling. Pitx2
      expression caused an upregulation of miR-200c and chromatin immunoprecipitation
      assays revealed endogenous Pitx2 binding to the miR-200c/141 promoter. A positive
      feedback loop was discovered between miR-200c and Bmp signaling. miR-200c/141
      induced expression of E-cadherin and the dental epithelial cell differentiation
      marker amelogenin. In addition, miR-203 expression was activated by endogenous
      Pitx2 and targeted the Bmp antagonist Bmper to further regulate Bmp signaling.
      miR-200c/141 knockout mice showed defects in enamel formation, with decreased E
      cadherin and amelogenin expression and increased noggin expression. Our in vivo
      and in vitro studies reveal a multistep transcriptional program involving the
      Pitx2:miR-200c/141:noggin regulatory pathway that is important in epithelial cell
      differentiation and tooth development. 

PMID- 23863489
TI  - Ceftriaxone pharmacokinetic properties during continuous veno-veno
      haemofiltration using an in vitro adult, paediatric and neonatal model.
AB  - During continuous venoveno haemofiltration (CVVH), extracorporeal drug clearance
      is dependant on blood flow, ultrafiltration rate, albumin binding, and the drug's
      molecular weight and volume of distribution. Drug doses are adjusted assuming
      reduced drug clearance by the renal system and CVVH. High volume haemofiltration,
      pre-dilution and different filter membranes can greatly alter drug clearance.
      Consequently, assessing the adequacy of cephalosporin dosing during CVVH is
      complex; under- or overdosing may occur. We studied the pharmacokinetic
      properties of ceftriaxone during CVVH in vitro. Renaflow filters were used to
      model 6, 20 and 50 kg patients. Each circuit and reservoir was prepared with a
      known volume of Hartmann's solution, human albumin solution 4.5% or blood. Pump
      speed and exchange rate were standardised for weight. Haemosol BO was used as the
      replacement fluid with 70% pre-dilution. Following paired sampling from the
      circuit and ultrafiltrate fluid, ceftriaxone was injected into the circuit.
      Paired samples were taken up to 720 minutes. Ceftraxione concentrations were
      determined using high performance liquid chromatography (HPLC). Maximum circuit
      concentrations (Cmax) at 2 minutes for albumin were 3.5, 2.65 and 4.85 mg/l, for
      blood were 4.5, 6.5 and 5.55 mg/l and for Hartmann's were 1.65, 2.95 and 3.65
      mg/l for 6 kg, 20 kg and 50 kg models. The sieving coefficients (Sc) from blood
      (ratio of mean concentrations in the ultrafiltrate/circuits samples) were 0.31
      and 0.51 with T1/2 (the half life) 62 and 20 minutes in the 6 kg and the 20 kg
      circuits, respectively. The data suggest in an in vitro model of ceftriaxone is
      rapidly cleared during CVVH. Albumin circuits had the lowest Sc and longest
      terminal T1/2, reflecting protein binding of the drug and suggest ceftriaxone
      clearance may be more rapid in hypoalbuminaemic patients. The Cmax was lower in
      the Hartmann circuits, possibly reflecting precipitation of the drug with calcium
      in this solution.

PMID- 23863490
TI  - Extracorporeal life support for acute respiratory distress syndrome due to severe
      Legionella pneumonia.
AB  - PURPOSE: Legionella is a common cause of community-acquired pneumonia (CAP) and
      is second only to Pneumococcal pneumonia as a cause of severe CAP that requires
      treatment in an intensive care unit. We report a case series of patients with
      severe Legionella pneumonia who developed the acute respiratory distress syndrome
      (ARDS), failed to improve with mechanical ventilation alone and required
      extracorporeal life support (ECLS). METHODS: We performed a retrospective study
      of all patients treated with ECLS at our institution for severe ARDS as a result
      of Legionella pneumonia from 1994 to 2006. RESULTS: A total of twelve patients
      with a diagnosis of Legionella pneumonia were treated with veno-venous (VV) ECLS
      over this time period. Nine of these twelve (75%) were successfully treated and
      weaned off ECLS and 8 patients (67%) survived to hospital discharge. Two (13%)
      died of multisystem organ failure, one patient (8%) died from global hypoxic
      encephalopathy and one (8%) was weaned from ECLS, but ultimately died of liver
      failure. Renal failure requiring some form of continuous dialysis occurred in
      seven patients (58%) and the survival for this sub-set of patients was 43%.
      CONCLUSIONS: Extracorporeal life support for severe ARDS associated with
      Legionella pneumonia is an effective treatment option when mechanical ventilation
      fails, especially when introduced early in the course.

PMID- 23863491
TI  - Assessment of team training in management of adverse acute events occurring
      during cardiopulmonary bypass procedure: a pilot study based on an animal
      simulation model (Fouilloux, Team training in cardiac surgery).
AB  - BACKGROUND: Successful cardiac surgery is highly dependent upon effective and
      efficient teamwork. Practical training and development will further enhance the
      team ability to react to a series of low-frequency occurring adverse events
      during cardiopulmonary bypass (CPB). One of our specialized educational programs
      focuses on training the whole team. This training is based on an original animal
      simulation model. The objective of this pilot study was to assess our method of
      training and learning in an attempt to optimize and improve team management and
      functioning. METHODS: Four members of the same cardiac surgery team joined our
      program. They performed a common procedure, with a cardiopulmonary bypass (CPB)
      circuit set up to produce several adverse incidents. Events management was
      analyzed and debriefed in technical and non-technical perspectives. RESULTS:
      Management of the adverse events was significantly improved. Discussion and
      debriefing time was fundamental in identifying the most appropriate management
      for each event. Rescue procedures were assimilated and team training was found to
      be effective, with the time reduced by up to 50% for 3 events and by up to 70%
      for air embolism. CONCLUSION: Our pilot program is an innovative, low-cost tool
      for the improvement of the management of adverse events occurring during CPB. It
      includes the different components of surgical education and training. Such an
      educational tool might be relevant for training. To confirm those encouraging
      results, it should be assessed in a larger surgical team panel. Further
      investigations are required for assessing efficiency in real conditions.

PMID- 23863492
TI  - Reliability of different body temperature measurement sites during aortic
      surgery.
AB  - OBJECTIVE: We retrospectively performed a comparative analysis of temperature
      measurement sites during surgical repair of the thoracic aorta. METHODS: Between
      January 2004 and May 2006, 22 patients (mean age: 63 +/- 12 years) underwent
      operations on the thoracic aorta with arterial cannulation of the aortic arch
      concavity and selective antegrade cerebral perfusion (ACP) during deep
      hypothermic circulatory arrest (HCA). Indications for surgical intervention were
      acute type A dissection in 14 (64%) patients, degenerative aneurysm in 6 (27%),
      aortic infiltration of thymic carcinoma in 1 (4.5%) and intra-aortic stent
      refixation in 1 (4.5%). Rectal, tympanic and bladder temperatures were evaluated
      to identify the best reference to arterial blood temperature during HCA and ACP.
      RESULTS: There were no operative deaths and the 30-day mortality rate was 13%
      (three patients). Permanent neurological deficits were not observed and transient
      changes occurred in two patients (9%). During re-warming, there was strong
      correlation between tympanic and arterial blood temperatures (r = 0.9541,
      p<0.001), in contrast to the rectal and bladder temperature (r = 0.7654, p = n.s;
      r = 0.7939, p = n.s., respectively). CONCLUSION: We conclude that tympanic
      temperature measurements correlate with arterial blood temperature monitoring
      during aortic surgery with HCA and ACP and, therefore, should replace bladder and
      rectal measurements.

PMID- 23863494
TI  - Our Connecticut quartet.

PMID- 23863495
TI  - Dentoalveolar segmental osteotomy for an ankylosed canine.

PMID- 23863493
TI  - Venoarterial extracorporeal membrane oxygenation for the management of massive
      amlodipine overdose.
AB  - A 50-year-old man was admitted to the intensive care unit with respiratory
      failure and shock after suffering a massive overdose of amlodipine, lisinopril
      and hydrochlorothiazide. Despite mechanical ventilation, vasopressors, calcium
      gluconate, hyperinsulinemia-euglycemia therapy, methylene blue and intravenous
      fat emulsion, the patient's respiratory and hemodynamic status deteriorated.
      Venoarterial extracorporeal membrane oxygenation (ECMO) was initiated to provide
      cardiopulmonary support in the setting of profound respiratory failure and
      refractory shock. The patient was placed on ECMO 19 hours after arrival to the
      hospital, after which vasopressor and ventilatory requirements decreased
      significantly. The patient was decannulated from ECMO after 8 days and was
      discharged home after a 56-day hospitalization. Early institution of ECMO should
      be considered for the management of respiratory failure and refractory shock in
      the setting of calcium channel blocker overdose when medical therapies are
      insufficient. 

PMID- 23863496
TI  - Nonextraction "surgery first" treatment of a skeletal Class III patient with
      severe maxillary crowding.

PMID- 23863497
TI  - Mechanics for treatment of impacted and ectopically erupted maxillary canines.

PMID- 23863498
TI  - Upper-molar intrusion using anterior palatal anchorage and the Mousetrap
      appliance.

PMID- 23863499
TI  - Securing a piggyback wire to an ectopic canine bracket.

PMID- 23863500
TI  - Indications, safety and image quality of cardiovascular magnetic resonance:
      experience in >5,000 North American patients.
AB  - BACKGROUND: CMR offers accurate assessment of structure and function with high
      resolution. Although the use of CMR has been well established in Europe,
      information is lacking for the extent of this emerging modality in North America.
      OBJECTIVES: This study aimed to summarize indications, safety, image quality,
      extent of contrast use and extent of stress tests performed in a high-volume CMR
      centre. METHODS: Consecutive patients scanned from July 2005 to November 2010
      were included, with duplicates and research subjects removed. Original clinical
      referrals were categorized into 10 main indications. RESULTS: Retrospective
      analysis was performed on 6463 patients (mean+/-SD age=50+/-17). The most common
      clinical indications were non-ischemic cardiomyopathies (28%), including
      myocarditis (18%), coronary artery disease (17%), ARVD and/or other RV disease
      (12%), and congenital heart disease (11%). Gadolinium-based contrast was given to
      89.5% of patients as part of their CMR protocol. Of 10.9% (703/6463) of patients
      that underwent stress CMR, adenosine was administered most commonly. Of 703
      patients, 1 (0.14%) suffered ventricular tachycardia during adenosine stress, and
      transient, asymptomatic AV block was occasionally observed. Moderate to severe
      complications after contrast agent administration occurred in 9 (0.16%) of 5782
      contrast-enhanced studies, characterized by nausea and vomiting in 6 (0.12%) and
      by symptoms of acute systemic allergic reaction in 2 (0.04%). Image quality was
      good (82.0%), moderate but diagnostic (16.6%) and poor in 1.4% of cases.
      CONCLUSION: In the high-volume CMR centre, main clinical indications were for
      myocarditis/cardiomyopathies, coronary artery disease and RV-related queries. CMR
      showed an excellent safety profile and high image quality in 99% of cases.

PMID- 23863501
TI  - Catheter ablation of hemodynamically unstable ventricular tachycardia with
      mechanical circulatory support.
AB  - BACKGROUND: Catheter ablation of hemodynamically unstable ventricular tachycardia
      (VT) is possible with mechanical circulatory support (MCS), little is known
      regarding the relative safety and efficacy of different supporting devices for
      such procedures. METHODS AND RESULTS: Sixteen consecutive patients (aged 63 +/-
      11 years with left ventricular ejection fraction of 20 +/- 9%) who underwent
      ablation of hemodynamically unstable VT were included in this study. Hemodynamic
      support included percutaneous (Impella(r) 2.5, n = 5) and implantable left
      ventricular assist devices (LVADs, n = 6) and peripheral cardiopulmonary bypass
      (CPB, n = 5). Except for 2 Impella cases, hemodynamic support was adequate (with
      consistent mean arterial pressure of > 60 mmHg) to permit sufficient activation
      mapping for ablation. In the Impella and CPB groups, mean time under hemodynamic
      support was 185 +/- 86 min, and time in VT was 78 +/- 36 min. Clinical VT could
      be terminated at least once by ablation in all patients except 1 case with
      Impella due to hemodynamic instability. Peri-procedural complications included
      hemolysis in 1 patient with Impella and surgical intervention for percutaneous
      Impella placement problems in another 2. The median number of appropriately
      delivered defibrillator therapies was significantly decreased from 6 in the month
      before VT ablation to 0 in the month following ablation (p = 0.001). CONCLUSIONS:
      Our data suggest that peripheral CPB and implantable LVAD provide adequate
      hemodynamic support for successful ablation of unstable VT. Impella(r) 2.5, on
      the other hand, was associated with increased risk of complications, and may not
      provide sufficient hemodynamic support in some cases.

PMID- 23863502
TI  - Immunogenicity of recombinant proteins consisting of Plasmodium vivax
      circumsporozoite protein allelic variant-derived epitopes fused with Salmonella
      enterica Serovar Typhimurium flagellin.
AB  - A Plasmodium falciparum circumsporozoite protein (CSP)-based recombinant fusion
      vaccine is the first malaria vaccine to reach phase III clinical trials.
      Resistance to infection correlated with the production of antibodies to the
      immunodominant central repeat region of the CSP. In contrast to P. falciparum,
      vaccine development against the CSP of Plasmodium vivax malaria is far behind.
      Based on this gap in our knowledge, we generated a recombinant chimeric protein
      containing the immunodominant central repeat regions of the P. vivax CSP fused to
      Salmonella enterica serovar Typhimurium-derived flagellin (FliC) to activate the
      innate immune system. The recombinant proteins that were generated contained
      repeat regions derived from each of the 3 different allelic variants of the P.
      vivax CSP or a fusion of regions derived from each of the 3 allelic forms. Mice
      were subcutaneously immunized with the fusion proteins alone or in combination
      with the Toll-like receptor 3 (TLR-3) agonist poly(I.C), and the anti-CSP serum
      IgG response was measured. Immunization with a mixture of the 3 recombinant
      proteins, each containing immunodominant epitopes derived from a single allelic
      variant, rather than a single recombinant protein carrying a fusion of regions
      derived from each of 3 allelic forms elicited a stronger immune response. This
      response was independent of TLR-4 but required TLR-5/MyD88 activation. Antibody
      titers significantly increased when poly(I.C) was used as an adjuvant with a
      mixture of the 3 recombinant proteins. These recombinant fusion proteins are
      novel candidates for the development of an effective malaria vaccine against P.
      vivax. 

PMID- 23863503
TI  - Limitations of the BP26 protein-based indirect enzyme-linked immunosorbent assay
      for diagnosis of Brucellosis.
AB  - Brucellosis is a serious zoonosis that occurs worldwide, and its diagnosis is
      typically based on the detection of antibodies against Brucella
      lipopolysaccharide (LPS). However, the specificity of the LPS-based test is
      compromised by cross-reactivity with Escherichia coli O157:H7 and Yersinia
      enterocolitica O:9. Also, diagnosis based on the LPS test cannot differentiate
      between vaccinated and infected individuals. The detection of the 26-kDa
      cytosoluble protein (BP26) antibody is considered an alternative that circumvents
      these drawbacks because it is exclusively expressed by infectious Brucella. A
      BP26-based enzyme-linked immunosorbent assay (ELISA) has been tried for the
      diagnosis of Brucella-infected animals and humans, but a few results showed that
      BP26 couldn't react with all Brucella-positive sera. In order to explore whether
      different animals could produce antibodies against BP26 after being infected with
      various Brucella species, we infected sheep, goats, and beef cattle with common
      virulent reference Brucella species. All sera were collected from the
      experimental animals and tested using both LPS-based ELISAs and BP26-based
      ELISAs. The results showed that all Brucella-infected individuals could produce
      high levels of antibodies against LPS, but only B. melitensis 16M- and B.
      melitensis M28-infected sheep and B. melitensis 16M- and B. abortus 2308-infected
      goats could produce antibodies against BP26. Therefore, we concluded that the
      BP26-based indirect ELISA (i-ELISA) showed both Brucella species and host
      specificity, which obviously limits its reliability as a substitute for the
      traditional LPS-based ELISA for the detection of brucellosis. 

PMID- 23863504
TI  - Human antibody neutralizes severe Fever with thrombocytopenia syndrome virus, an
      emerging hemorrhagic Fever virus.
AB  - Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered
      member of the Bunyaviridae family, is the causative agent of an emerging
      hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective
      therapies against SFTS. In this study, a combinatorial human antibody library was
      constructed from the peripheral lymphocytes of 5 patients who had recovered from
      SFTS. The library was screened against purified virions for the production of
      single-chain variable-region fragments (ScFv). Of the 6 positive clones, one
      clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV
      infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the
      clinical isolates of SFTSV tested, which were isolated from patients in China
      from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain
      of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the
      interactions between the Gn protein and the cellular receptor, indicating that
      inhibition of virus-cell attachment is its main mechanism. These data suggest
      that MAb 4-5 can be used as a promising candidate molecule for immunotherapy
      against SFTSV infection. 

PMID- 23863505
TI  - Modulation of chicken intestinal immune gene expression by small cationic
      peptides as feed additives during the first week posthatch.
AB  - We have been investigating modulation strategies tailored around the selective
      stimulation of the host's immune system as an alternative to direct targeting of
      microbial pathogens by antibiotics. One such approach is the use of a group of
      small cationic peptides (BT) produced by a Gram-positive soil bacterium,
      Brevibacillus texasporus. These peptides have immune modulatory properties that
      enhance both leukocyte functional efficiency and leukocyte proinflammatory
      cytokine and chemokine mRNA transcription activities in vitro. In addition, when
      provided as a feed additive for just 4 days posthatch, BT peptides significantly
      induce a concentration-dependent protection against cecal and extraintestinal
      colonization by Salmonella enterica serovar Enteritidis. In the present studies,
      we assessed the effects of feeding BT peptides on transcriptional changes on
      proinflammatory cytokines, inflammatory chemokines, and Toll-like receptors (TLR)
      in the ceca of broiler chickens with and without S. Enteritidis infection. After
      feeding a BT peptide-supplemented diet for the first 4 days posthatch, chickens
      were then challenged with S. Enteritidis, and intestinal gene expression was
      measured at 1 or 7 days postinfection (p.i.) (5 or 11 days of age). Intestinal
      expression of innate immune mRNA transcripts was analyzed by quantitative real
      time PCR (qRT-PCR). Analysis of relative mRNA expression showed that a BT peptide
      supplemented diet did not directly induce the transcription of proinflammatory
      cytokine, inflammatory chemokine, type I/II interferon (IFN), or TLR mRNA in
      chicken cecum. However, feeding the BT peptide-supplemented diet primed cecal
      tissue for increased (P <= 0.05) transcription of TLR4, TLR15, and TLR21 upon
      infection with S. Enteritidis on days 1 and 7 p.i. Likewise, feeding the BT
      peptides primed the cecal tissue for increased transcription of proinflammatory
      cytokines (interleukin 1beta [IL-1beta], IL-6, IL-18, type I and II IFNs) and
      inflammatory chemokine (CxCLi2) in response to S. Enteritidis infection 1 and 7
      days p.i. compared to the chickens fed the basal diet. These small cationic
      peptides may prove useful as alternatives to antibiotics as local immune
      modulators in neonatal poultry by providing prophylactic protection against
      Salmonella infections. 

PMID- 23863506
TI  - Long-term protective immunity from an influenza virus-like particle vaccine
      administered with a microneedle patch.
AB  - Skin vaccination with influenza virus-like particles (VLPs) using microneedles
      has been shown to induce protection similar to or better than that induced by
      intramuscular immunization. In this study, we examined the long-term protective
      efficacy of influenza (H1N1 A/PR/8/34) VLPs after skin vaccination using
      microneedle patches coated with the vaccine. Microneedle vaccination of mice in
      the skin induced 100% protection against lethal challenge infection with
      influenza A/PR/8/34 virus 14 months after a single vaccine dose. Influenza virus
      specific total IgG response and hemagglutination inhibition (HAI) titers were
      maintained at high levels for over 1 year after microneedle vaccination.
      Microneedle vaccination also induced substantial levels of lung IgG and IgA
      antibody responses, and antibody-secreting plasma cells from spleen and bone
      marrow, as well as conferring effective control of lung viral loads, resulting in
      complete protection 14 months after vaccination. These strong and long-lasting
      immune responses were enabled in part by stabilization of the vaccine by
      formulation with trehalose during microneedle patch fabrication. Administration
      of the stabilized vaccine using microneedles was especially effective at enabling
      strong recall responses measured 4 days after lethal virus challenge, including
      increased HAI and antibody-secreting cells in the spleen and reduced viral titer
      and inflammatory response in the lung. The results in this study indicate that
      skin vaccination with VLP vaccine using a microneedle patch provides long-term
      protection against influenza in mice. 

PMID- 23863507
TI  - Long-term survival and outcome of patients originally given Mycobacterium vaccae
      for metastatic malignant melanoma.
AB  - BACKGROUND: The long-term prognosis of patients with stage IV AJCC melanoma is
      extremely poor. We have previously published short-term clinical outcome and
      immunological responses to a heat killed Mycobacterium vaccae-based vaccine.
      RESULTS: In this study we report on a better than expected long-term survival (3
      y DSS 29.6%, 5-y, and 7-y DSS both 23.9%) relative to historical controls in the
      patients who received the vaccine in these trials, published in 1999 and 2003.
      Although the complete or partial response was only 10%, it was the remarkable
      response to other interventions upon relapse, such as surgery and radiotherapy
      followed by stable disease that was previously unexpected. METHODS: We reviewed
      the outcome of 72 patients who were treated with M. vaccae for metastatic
      melanoma between January 1996 and July 2004. CONCLUSION: Given this remarkable
      outcome in stage IV metastatic melanoma and its lack of toxicity we propose that
      this would make a promising candidate for randomized trials for stage III fully
      resected melanoma.

PMID- 23863508
TI  - The distribution of unique green wavelengths and its relationship to macular
      pigment density.
AB  - Monochromatic unique green (UG) is more variable across the population than any
      other unique hue. Some researchers have reported that this broad distribution of
      UG settings is bimodal and that the distribution results from the superposition
      of two or more subpopulations. We have investigated this claim using a Wright
      colorimeter to measure the unique green wavelength of 58 participants and we have
      analyzed previous unique green literature by applying a rigorous statistical test
      to historical datasets. We have also explored the possibility that individual
      differences in macular pigment density may be responsible for the variation in
      unique green wavelength. Our results indicate that unique green wavelengths in
      our population are distributed unimodally and are correlated positively with
      macular pigment density; individuals with a higher density of macular pigment
      select longer wavelengths of light as unique green than individuals with a lower
      density of macular pigment. We model this effect using simulations of
      monochromatic unique green matching to broadband illuminations and show that
      matches in the region at approximately 500 nm exhibit particularly high variance
      both with respect to macular pigment density and also with respect to the precise
      shape of the broadband reference exemplar spectrum. 

PMID- 23863509
TI  - Attentional synchrony and the influence of viewing task on gaze behavior in
      static and dynamic scenes.
AB  - Does viewing task influence gaze during dynamic scene viewing? Research into the
      factors influencing gaze allocation during free viewing of dynamic scenes has
      reported that the gaze of multiple viewers clusters around points of high motion
      (attentional synchrony), suggesting that gaze may be primarily under exogenous
      control. However, the influence of viewing task on gaze behavior in static scenes
      and during real-world interaction has been widely demonstrated. To dissociate
      exogenous from endogenous factors during dynamic scene viewing we tracked
      participants' eye movements while they (a) freely watched unedited videos of real
      world scenes (free viewing) or (b) quickly identified where the video was filmed
      (spot-the-location). Static scenes were also presented as controls for scene
      dynamics. Free viewing of dynamic scenes showed greater attentional synchrony,
      longer fixations, and more gaze to people and areas of high flicker compared with
      static scenes. These differences were minimized by the viewing task. In
      comparison with the free viewing of dynamic scenes, during the spot-the-location
      task fixation durations were shorter, saccade amplitudes were longer, and gaze
      exhibited less attentional synchrony and was biased away from areas of flicker
      and people. These results suggest that the viewing task can have a significant
      influence on gaze during a dynamic scene but that endogenous control is slow to
      kick in as initial saccades default toward the screen center, areas of high
      motion and people before shifting to task-relevant features. This default-like
      viewing behavior returns after the viewing task is completed, confirming that
      gaze behavior is more predictable during free viewing of dynamic than static
      scenes but that this may be due to natural correlation between regions of
      interest (e.g., people) and motion. 

PMID- 23863510
TI  - Learning diagnostic features: the delta rule does Bubbles.
AB  - It has been shown (Murray & Gold, 2004a) that the Bubbles paradigm for studying
      human perceptual identification can be formally analyzed and compared to reverse
      correlation methods when the underlying identification model is conceived as a
      linear amplifier (LAM). However the usefulness of a LAM for characterizing human
      perceptual identification mechanisms has subsequently been questioned (Gosselin &
      Schyns, 2004). In this article we show that a simple linear model that is
      formally analogous to the LAM--a linear perceptron trained with the delta rule-
      can make sense of several Bubbles experiments in the context of letter
      identification. Specifically, an analysis of input-output connection weights
      after training revealed that the most positive weights clustered around letter
      parts in a way that mimicked the diagnostic parts of letters revealed by the
      Bubbles technique (Fiset et al., 2008). Our results suggest that linear observer
      models are indeed unreasonably effective, at least as first approximations to
      human letter identification mechanisms.

PMID- 23863512
TI  - Two primes priming: does feature integration occur before response activation?
AB  - Responses to a target can be sped up or slowed down by a congruent or incongruent
      prime, respectively. Even though presentations are rapid, the prime and the
      target are thought to activate motor responses in strict sequence, with prime
      activation preceding target activation. In feature fusion, the opposite seems to
      be the case. For example, a vernier offset to the left is immediately followed by
      a vernier offset to the right at the same location. The two verniers are not
      perceived as two elements in sequence but as a single, aligned vernier. Here, we
      ask the question as to how features are integrated: before or after motor
      activation? We presented two vernier primes with opposite offset directions
      preceding a single vernier target. No priming effect occurred when the vernier
      primes were presented at the same location, indicating that verniers integrate
      before motor activation. There was also no priming effect when the primes were
      presented simultaneously at different locations, indicating that there is an
      integration stage different from the perceptual fusion stage. When the second
      prime is delayed, it determines priming, even for very long delays. To explain
      these long integration times, we argue that there is a buffer preceding motor
      activation. 

PMID- 23863511
TI  - Aftereffect of perceived regularity.
AB  - Regularity is a ubiquitous feature of the visual world. We demonstrate that
      regularity is an adaptable visual dimension: The perceived regularity of a
      pattern is reduced following adaptation to a pattern with a similar or greater
      degree of regularity. Stimuli consisted of 7*7 element arrays arranged on square
      grids presented in a circular aperture. The position of each element was randomly
      jittered from its baseline position by an amount that determined its degree of
      irregularity. The elements of the pattern consisted of dark Gaussian blobs (GBs),
      difference of Gaussians (DOGs), or random binary patterns (RBPs). Observers
      adapted for 60 s to either a single pattern or a pair of patterns with particular
      regularities, and the perceived regularities of subsequently presented test
      patterns were measured using a conventional staircase matching procedure. We
      found that the regularity aftereffect (RAE) was unidirectional: Adaptation only
      caused test patterns to appear less regular. We also found that RAEs transferred
      from GB adaptors to both DOG and RBP test patterns and from DOG and RBP adaptors
      to GB patterns. We suggest that regularity is coded by the peakedness in the
      distribution of spatial-frequency channel responses across scale, and that the
      RAE is a result of a flattening of this distribution by adaptation. Thus, the RAE
      may be a consequence of contrast normalization, and an example of norm-based
      coding where irregularity is the norm.

PMID- 23863513
TI  - In situ TEM observation of buffering the anode volume change by using NiTi alloy
      during electrochemical lithiation/delithiation.
AB  - A novel Ti3Sn/NiTi shape memory alloy anode with a sandwich structure was
      fabricated by arc melting. In order to characterize in situ the Ti3Sn/NiTi anode
      microstructure changes and phase transformations during cycling, a nanoscale
      lithium battery was set up inside a transmission electron microscope, which
      consists of Li metal as the cathode, the native Li2O layer on the surface of Li
      metal as the solid electrolyte, and the Ti3Sn/NiTi as the anode. Only the Ti3Sn
      intermetallic compound experienced the electrochemical reaction, while the NiTi
      alloy (inactive with Li(+)) was applied for buffering the Ti3Sn volume change
      during cycling. An obvious reaction front of Ti3Sn migrated from one end to the
      other during lithiation, which can also return after delithiation. It provides
      direct evidence that the NiTi alloy can effectively accommodate the anode volume
      change during electrochemical lithiation and delithiation. 

PMID- 23863515
TI  - Intracerebral and spinal cord syphilitic gummata in an HIV-negative man: a case
      report.
AB  - We present a case of an HIV-negative individual who presented with worsening
      central and peripheral neurological symptoms and signs. Clinical, serological,
      histopathological, and radiological features were in keeping with concurrent
      cerebral and spinal cord syphilitic gummata, a tertiary manifestation of
      syphilis. Clinical improvement occurred after treatment of neurosyphilis. 

PMID- 23863514
TI  - Drug-using male clients of female sex workers who report being paid for sex:
      HIV/sexually transmitted infection, demographic, and drug use correlates.
AB  - BACKGROUND: Research has focused on male clients of female sex workers (FSWs) and
      their risk for HIV/sexually transmitted infections (STIs). However, it is unclear
      whether the commercial sex behaviors of these men are limited to paying for sex
      or whether they may also be paid for sex themselves. METHODS: We analyzed the
      interview data and HIV/STI test results from 170 drug-using male clients of FSWs
      in Tijuana, Mexico, to determine the extent to which these men report being paid
      for sex and the association with positive HIV/STI results. RESULTS: More than one
      quarter of men reported having been paid for sex in the past 4 months. In a
      multivariate logistic regression model, reporting having been paid for sex was
      significantly associated with testing positive for any HIV/STI (adjusted odds
      ratio [AdjOR], 3.53; 95% confidence interval [CI], 1.33-9.35), being bisexual
      (AdjOR, 15.59; 95% CI, 4.81-50.53), injection drug use in the past 4 months
      (AdjOR, 2.65; 95% CI, 1.16-6.03), and cocaine use in the past 4 months (AdjOR,
      2.93; 95% CI, 1.22-7.01). CONCLUSIONS: Findings suggest that drug-using male
      clients of FSWs may be characterized by unique risk profiles that require
      tailored HIV prevention interventions.

PMID- 23863516
TI  - Anogenital warts: influence on quality of life in Dutch soldiers.
AB  - BACKGROUND: Anogenital warts are one of the most prevalent sexually transmitted
      virus infections in the Netherlands and cause frustration, shame, and even
      depression. This study was performed to determine the effect of having anogenital
      warts on the quality of life in Dutch soldiers with the use of a dermatology
      specific quality of life (QoL) questionnaire. METHODS: We used the Skindex-29 QoL
      questionnaire in 100 predominantly heterosexual soldiers with clinically
      confirmed first episode of condylomata acuminate in this study. RESULTS: Results
      confirmed that first episodes of anogenital warts cause high mean scores on
      subscale Emotions with lower scores on the subscales Symptoms and Functioning.
      Sex, age, educational level, anatomical site, or number of anatomical sites did
      not influence the outcome in this study. CONCLUSIONS: Having anogenital warts
      influences QoL, especially with regard to intimacy, shame, and concern. Our data
      show that the Skindex-29 QoL questionnaire can be easily used in these patients
      with good internal consistency. Clinicians should be aware of the great emotional
      impact of anogenital warts on their patients.

PMID- 23863517
TI  - Integration of family planning services into a sexually transmitted disease
      clinic setting.
AB  - BACKGROUND: Sexually transmitted diseases (STDs) and unintended pregnancy are
      significant and costly public health concerns. Integrating family planning
      services (FPS) into STD visits provides an opportunity to address both concerns
      simultaneously. Our objectives were to create an electronic eligibility reminder
      to identify male and female patients eligible for FPS during an STD clinic visit
      and measure FPS use, additional cost of integrated services, and patient/provider
      satisfaction and to explore the impact on incident pregnancy and STDs. METHODS:
      Quasi-experimental design compared enrollment and patient/provider satisfaction
      before (2008) and after implementation (2010). Incident pregnancy and STD 12
      months after the initial visit before and after were explored. Time and cost were
      calculated. Quantitative and qualitative analyses were performed. RESULTS: A
      total of 9695 clients (male, 5842; female, 3853) in 2008 and 10,021 clients
      (male, 5852; female, 4169) in 2010 were eligible for FPS. Enrollment in FPS
      increased (2008: 51.6%, 2010: 95.3%; P < 0.01). Total additional cost was
      US$29.25/visit, and additional staff time was 4.01 minutes for integrated visits.
      Staff satisfaction increased and client satisfaction remained high. Among women
      returning within 12 months (39.6% in 2008, 37.1% in 2010), pregnancies were lower
      among enrolled versus nonenrolled women for 2008 (7.7% vs. 19.5%, P < 0.01) and
      2010 (13.1% vs. 25.9%, P = 0.05). Incident STDs did not differ. DISCUSSION: An
      electronic eligibility reminder of FPS increased FPS use. Integration of FPS with
      STD services is feasible, is well accepted, and increases costs minimally.
      Integration may reduce pregnancy rates without increasing STD rates.

PMID- 23863518
TI  - Interval exercise training in cystic fibrosis -- effects on exercise capacity in
      severely affected adults.
AB  - The aims of the present study were to investigate the effects of IT on lung
      function power (P) and oxygen uptake (VO2) at peak performance (peak) and
      ventilatory anaerobic threshold (VAT) in CF patients who were unable to
      participate in a standard exercise program (SEP) and to compare these IT
      responses with corresponding effects in CF patients performing SEP. 20 patients
      (FEV1 25.5 +/- 7.5%; pred; SpO2 < 90% at rest or P lower than 0.3 W/kg) who were
      unable to participate in SEP were allocated to IT (5 * 20 min weekly). 23
      patients (FEV1 31.6 +/- 4.2%; p < 0.05) did 5 * 45 min per week of SEP. Lung
      function remained unchanged in both groups. VO2peak and PVAT increased in both
      groups (p < 0.05). However, only after the SEP an increase in Ppeak (p < 0.05)
      and only after IT a higher VO2VAT (p < 0.05) were found. Compared to SEP, IT
      improved submaximal exercise capacity to a greater extent whereas responsiveness
      on peak performance was higher in SEP. This seems to indicate a specific
      potential of IT for positive peripheral muscular adaptations in spite of
      diminishing potential of pulmonary improvement. IT represents an alternative,
      effective and safe training regimen with patients with CF and severe lung
      disease, with a greater potential than SEP.

PMID- 23863519
TI  - Small-world network properties in prefrontal cortex correlate with predictors of
      psychopathology risk in young children: a NIRS study.
AB  - Near infrared spectroscopy (NIRS) is an emerging imaging technique that is
      relatively inexpensive, portable, and particularly well suited for collecting
      data in ecological settings. Therefore, it holds promise as a potential
      neurodiagnostic for young children. We set out to explore whether NIRS could be
      utilized in assessing the risk of developmental psychopathology in young
      children. A growing body of work indicates that temperament at young age is
      associated with vulnerability to psychopathology later on in life. In particular,
      it has been shown that low effortful control (EC), which includes the focusing
      and shifting of attention, inhibitory control, perceptual sensitivity, and a low
      threshold for pleasure, is linked to conditions such as anxiety, depression and
      attention deficit hyperactivity disorder (ADHD). Physiologically, EC has been
      linked to a control network spanning among other sites the prefrontal cortex.
      Several psychopathologies, such as depression and ADHD, have been shown to result
      in compromised small-world network properties. Therefore we set out to explore
      the relationship between EC and the small-world properties of PFC using NIRS.
      NIRS data were collected from 44 toddlers, ages 3-5, while watching naturalistic
      stimuli (movie clips). Derived complex network measures were then correlated to
      EC as derived from the Children's Behavior Questionnaire (CBQ). We found that
      reduced levels of EC were associated with compromised small-world properties of
      the prefrontal network. Our results suggest that the longitudinal NIRS studies of
      complex network properties in young children hold promise in furthering our
      understanding of developmental psychopathology. 

PMID- 23863520
TI  - Multi-detector-row computed tomography imaging of variant skull base foramina.
AB  - Several inconstant skull base foramina can be observed on multi-detector-row
      computed tomographic studies. These include the meningo-orbital foramen, foramen
      of Vesalius, canaliculus innominatus, palatovaginal canal, persistent
      craniopharyngeal canal, transsphenoidal canal, canalis basilaris medianus, and
      fossa navicularis. Although many of these foramina are simply incidental
      findings, there may be associated anomalies and important clinical implications.
      The multi-detector-row computed tomographic features of variant skull base
      foramina are depicted and discussed in this article. 

PMID- 23863521
TI  - National variation of technical factors in computed tomography of the head.
AB  - OBJECTIVE: The objectives of this study were to describe head computed tomography
      (CT) technical factors used in the United States; assess guideline compliance and
      variability by sex, geographic region, institution, and manufacturer; and compare
      with NEXT (Nationwide Evaluation of X-ray Trends) survey. METHODS: Two thousand
      thirty-five head CT studies from 895 sites were analyzed. Peak kilovoltage,
      exposure, slice and image number, slice thickness, field of view, interslice gap,
      reformations, examination inclusiveness, use of contrast, and reconstruction
      filter were compared by sex, geographic region, institution type, and
      manufacturer. RESULTS: One hundred twenty to 140 kVp (peak kilovoltage) was used
      by 99.8% of the sites. There was no correlation between mAs and kVp. There was a
      30-fold increase in number of images and nearly 9-fold increase in number of
      slices from least to most. Nearly 4% use slice thickness and interslice gap
      greater than guidelines. There were significant regional differences in field of
      view, image number, and slice thickness. Some variation related to manufacturers
      was found. Minor difference was also found between academic and nonacademic
      institutions. There were significant differences in kVp and mAs compared with
      NEXT. CONCLUSIONS: Significant variations in head CT technique exist in the
      United States.

PMID- 23863522
TI  - 3-T magnetic resonance angiography in primary angiitis of the central nervous
      system.
AB  - OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare
      disease characterized by an inflammatory process of intracranial vessels.
      Magnetic resonance angiography (MRA) (3 T) offers increased signal-to-noise ratio
      and background suppression, leading to better depiction of the intracranial
      vessels. The aim of our work was to compare the sensitivity of 3-T MRA to that of
      1.5-T MRA in the diagnosis of PACNS. METHODS: Eight patients with PACNS and signs
      of angiitis at digital subtraction angiography (DSA) underwent MRA at 1.5 and 3
      T. Magnetic resonance angiograms obtained with time-of-flight (TOF) technique
      were evaluated for the presence of stenosis with respect to DSA. RESULTS: In
      PACNS patients, DSA identified 827 intracranial stenoses. Sensitivity for vessel
      stenosis of 3-T TOF MRA was 47% and 14% for 1.5-T TOF. CONCLUSIONS: Time-of
      flight MRA at 3 T improved the sensitivity of MRA in the noninvasive preliminary
      evaluation of patients with PACNS.

PMID- 23863523
TI  - Correlation of mucositis during head and neck radiotherapy with computed
      tomography perfusion imaging of the oropharyngeal mucosa.
AB  - OBJECTIVE: The objective of this study was to correlate changes in computed
      tomography perfusion (CTP) parameters in the oropharyngeal mucosa following start
      of radiotherapy (RT) with acute mucositis in head and neck cancer patients.
      METHODS: Fifteen patients were prospectively evaluated with serial CTP imaging.
      Computed tomography perfusion studies were obtained before RT; at weeks 2, 4, and
      6 during RT; and 6 weeks after completion of RT. RESULTS: At week 2 during RT,
      mean transition time increased to 13.9% and 261.8% in patients with and without
      mucositis, respectively (P = 0.024). At week 6 of RT, patients with grade 3
      mucositis had a 325.4% increase in blood flow compared with a 58.3% increase in
      patients with grade 0-2 mucositis (P = 0.039). Mean transition time decreased by
      29.9% and increased by 187.4% in patients with grade 3 and grade 0-2 mucositis,
      respectively (P = 0.025). CONCLUSIONS: Mean transition time and blood flow
      changes in the oropharyngeal mucosa correlated with the incidence and severity of
      RT-related mucositis.

PMID- 23863524
TI  - Utility of diffusion-weighted imaging in differentiating malignant from benign
      thyroid nodules with magnetic resonance imaging and pathologic correlation.
AB  - OBJECTIVE: The objective of this study was to evaluate the role of magnetic
      resonance diffusion-weighted imaging (DWI) in differentiating malignant from
      benign thyroid nodules. METHODS: The prospective study included 111 consecutive
      patients with solitary thyroid nodules (23 malignant and 88 benign nodules) who
      underwent DWI. The DWI signal and apparent diffusion coefficient (ADC) values of
      the nodules were determined and correlated with the histopathologic findings.
      RESULTS: The majority (65%) of malignant thyroid nodules showed slightly
      hyperintense, and the majority (69%) of benign nodules were hyperintense on DWI
      (P < 0.01). The ADC values were lower in the thyroid cancer than in the adenoma
      and nodular goiter (P < 0.05). When the b factor was 500 s/mm, an ADC value of
      1.704 * 10 mm/s can be threshold differentiating malignant from benign nodules,
      with 92% sensitivity, 88% specificity, and 87% accuracy. The higher cell density
      and more severe desmoplastic response were the causes of the lower ADC value of
      thyroid cancer. CONCLUSION: Diffusion-weighted imaging can be a promising
      noninvasive imaging to discriminate malignant from benign nodules.

PMID- 23863525
TI  - Three-phase parathyroid 4-dimensional computed tomography initial experience:
      inexperienced readers have high accuracy and high interobserver agreement.
AB  - OBJECTIVE: Multiphase multidetector contrast-enhanced parathyroid CT (4
      dimensional computed tomography [4D-CT]) is an emerging tool for evaluating
      patients with primary hyperparathyroidism. Our goal was to describe the initial
      performance of 2 inexperienced readers in interpretation of 4D-CT. METHODS:
      Twenty-three subjects who received 4D-CT and successful surgical exploration were
      studied (14 initial and 9 repeat explorations; 15 single-gland disease and 8
      multigland disease) A staff neuroradiologist prospectively interpreted all
      studies, and a neuroradiology fellow retrospectively interpreted all studies;
      their results were compared with the surgical findings for each side of the neck
      separately. RESULTS: The prospective readings were 78% accurate overall, 97%
      accurate in the subset of single-gland disease cases, and 89% accurate in re
      exploration cases. There was 91% concordance in interpretation between observers,
      with kappa of 0.83. CONCLUSIONS: Initial results after implementation of 4D-CT
      show high accuracy of interpretation for inexperienced observers, comparable to
      published data, and high interobserver agreement.

PMID- 23863526
TI  - Two-phase computed tomography study of warthin tumor of parotid gland:
      differentiation from other parotid gland tumors and its pathologic explanation.
AB  - OBJECTIVE: The objective of this study was to define the radiological
      characteristics of 2-phase computed tomography (CT) of parotid gland Warthin
      tumors (WTs) with a pathologic basis for these findings. METHODS: We
      prospectively enrolled 116 patients with parotid gland tumor who underwent
      preoperative 2-phase CT scans(scanning delays of 30 and 120 seconds). The
      attenuation changes and enhancement patterns were analyzed according to
      pathology. We also evaluated size-matched samples of WTs and pleomorphic adenoma
      by staining CD31, vascular endothelial growth factor-receptor 2, collagen IV, and
      smooth muscle actin. RESULTS: Computed tomography numbers in WTs were
      significantly higher than those in other tumors in early-phase scans and lower in
      delayed scans. Pathologically, CD31(+) blood vessel area was significantly higher
      in WTs than in pleomorphic adenomas. In addition, WTs had an extensive capillary
      network and many leaky blood vessels. CONCLUSIONS: The enhancement pattern of
      early fill-in and early washout is the typical finding of WTs on 2-phase CT
      scans, which may be attributed pathologically to abundant blood vessel and
      extensive capillary network.

PMID- 23863527
TI  - Perineural tumor spread to the oculomotor (CN III) nerve.
AB  - Our purpose was to present 3 cases of perineural tumor spread (PNS) to the
      oculomotor (CN III) nerve. To our knowledge, PNS to CN III has not been
      previously reported. In the course of advanced PNS, typically with involvement of
      the cavernous sinus, tumor may spread in a retrograde fashion to involve CN III
      in the interpeduncular fossa and can even invade the brainstem. 

PMID- 23863528
TI  - Adrenal masses: contemporary imaging characterization.
AB  - Adrenal masses are among the most common incidentally discovered lesions on cross
      sectional imaging with estimated incidence of approximately 5%. In addition,
      adrenal lesions can also be detected as part of an endocrinology workup with
      suspicion of a functional adrenal mass. Regardless of the source of detection, it
      is crucial to differentiate a benign from a malignant process and furthermore
      utilize characteristic imaging appearance of different adrenal masses to
      facilitate diagnosis and guide management. There are numerous imaging protocols
      and postprocessing methods for evaluation of adrenal masses with high sensitivity
      and specificity with small differences between institutions. Currently, the most
      widely used imaging modality for evaluation of adrenal mass is computed
      tomography without and with contrast washout assessment. In this article, we
      review diagnostic approaches to adrenal masses using computed tomography and
      magnetic resonance imaging techniques and present imaging strategies utilized at
      our institution. The advantages and challenges of these imaging modalities for
      evaluation of adrenal pathologies are discussed. 

PMID- 23863529
TI  - Second-generation dual-energy computed tomography of the abdomen: radiation dose
      comparison with 64- and 128-row single-energy acquisition.
AB  - PURPOSE: This study was designed to compare the radiation dose in abdominal dual
      energy (DE) and single-energy (SE) acquisitions obtained in clinical practice
      with a second-generation DE computed tomography (DECT) and to analyze the dose
      variation in comparison with an SE acquisition performed with a 64-row SECT
      (SECT). METHODS: A total of 130 patients divided into 2 groups underwent
      precontrast and portal abdominal 128-row CT examination. In group A, DE portal
      acquisition was performed using a detector configuration of 2 * 40 * 0.6 mm, tube
      A at 80 kVp and a reference value of 559 mAs, tube B at 140 kVp and a reference
      value of 216 mAs, pitch 0.6, and online dose modulation; group B underwent SE
      portal acquisition using a detector configuration of 64 * 0.6 mm, 120 kVp and a
      reference value of 180 mAs, pitch 0.75, and online dose modulation. Group C
      consisted of 32 subjects from group A previously studied with 64-row SECT using
      the following parameters: detector configuration 64 * 0.6 mm, 120 kVp and a
      reference value of 180 mAs, pitch 0.75, and online dose modulation. In each
      group, the portal phase dose-length product and radiation dose (mSv) were
      calculated and normalized for a typical abdominal acquisition of 40 cm. RESULTS:
      After normalization to standard 40-cm acquisition, a dose-length product of 599.0
      +/- 133.5 mGy . cm (range, 367.5 +/- 1231.2 mGy . cm) in group A, 525.9 +/- 139.2
      mGy . cm (range, 215.7-882.8 mGy . cm) in group B, and 515.9 +/- 111.3 mGy . cm
      (range, 305.5-687.2 mGy . cm) in group C was calculated for portal phase
      acquisition.A significant radiation dose increase (P < 0.05) was observed in
      group A (10.2 +/- 2.3 mSv) compared with group B (8.9 +/- 2.4) and group C (8.8
      +/- 1.9 mSv). No significant difference (P > 0.05) was reported between SE 64-
      and 128-row acquisitions. A significant positive correlation between radiation
      dose and body mass index was observed in each group (group A, r = 0.59, P <
      0.0001; group B, r = 0.35, P < 0.0001; group C, r = 0.20, P = 0.0098).
      CONCLUSIONS: In clinical practice, abdominal DECT acquisition shows a significant
      but minimal radiation dose increase, on the order of 1 mSv, compared with 64- and
      128-row SE acquisition. The slightly increased radiation dose can be justified if
      the additional information obtained using a spectral imaging approach directly
      impacts on patient management or reduce the overall radiation dose with the
      generation of virtual unenhanced images, which can replace the precontrast
      acquisition.

PMID- 23863530
TI  - Evaluation of dose modulation software through the assessment of body mass index,
      radiation dose and image noise.
AB  - PURPOSE: This study attempts to establish a quantitative link between a patient's
      body mass index (BMI), the delivered radiation dose, and the image noise.
      METHODS: The CARE Dose4D computed tomography (CT) acquisitions from 206 patients
      undergoing "eyes-to-thighs" contrast-enhanced positron emission tomography/CT
      studies were retrospectively examined. Computed tomography dose index volume
      (CTDIVOL), mAs, and dose-length product were recorded from the dose report card.
      The image noise was quantified by evaluating the SD of regions of interest placed
      over the contrast enhanced aorta. RESULTS: The multivariate regressions f(BMI,
      mAs) and f(BMI, CTDIVOL) had R values of 0.4840 and 0.4802, respectively.
      Unpaired t tests demonstrate that statistically significant difference in image
      noise required more than 12.17 kg/m of separation between the average BMI values
      for the groups compared. CONCLUSIONS: The evaluation of image noise with BMI and
      CTDIVOL or mAs is a means to evaluate the consistency of dose modulation
      software. There is considerable variability in the radiation dose generated by
      the CARE Dose4D software.

PMID- 23863531
TI  - Individualized kV selection and tube current reduction in excretory phase
      computed tomography urography: potential for radiation dose reduction and the
      contribution of iterative reconstruction to image quality.
AB  - OBJECTIVE: The objective of this study was to analyze radiation dose reduction
      and image quality by combining automated kV selection, tube current reduction,
      and iterative reconstruction. METHODS: This was a retrospective analysis of the
      excretory phase of 55 patients with 2 computed tomography urography examinations:
      automated kV selection with tube current reduction ("low-dose protocol": with
      filtered back projection vs iterative reconstruction) and routine dose
      examinations. Image quality was analyzed blindly and in side-by-side analyses, in
      addition to quantitative measurements. RESULTS: Low-dose protocol median dose
      change was -40% (-10.7 to +12.9 mGy); 100 kV was autoselected in 44 (80%) of 55
      patients (body mass index range, 19-36 kg/m) with mean dose reduction of 42.5%.
      Whereas up to 19% of low-dose images with filtered back projection were inferior
      by blinded review (P < 0.001), low-dose iterative reconstruction images were not
      rated inferior (P = 1.0). CONCLUSIONS: The combination of iterative
      reconstruction, automated kV selection, and tube current reduction results in
      radiation dose reduction with preserved image quality and diagnostic confidence.

PMID- 23863532
TI  - Focal liver lesion classification and characterization in noncirrhotic liver: a
      prospective comparison of diffusion-weighted magnetic resonance-related
      parameters.
AB  - PURPOSE: The objective of this study was to prospectively verify if diffusion
      weighted magnetic resonance (DwMR)-related parameters such as perfusion fraction
      (f) and slow diffusion coefficient (D), according to Le Bihan theory, are more
      effective than apparent diffusion coefficient (ADC) for classification and
      characterization of the more frequent focal liver lesions (FLLs) in noncirrhotic
      liver. METHODS: Sixty-seven patients underwent standard liver magnetic resonance
      imaging (MRI) and free-breath multi-b DwMR study. Two regions of interest were
      defined by 2 observers, including 1 FLL for each patient (21 hemangiomas, 21
      focal nodular hyperplasias, 25 metastases) and part of surrounding parenchyma,
      respectively. For every FLL, D, f, and ADC were estimated both as absolute value
      and as ratio between FLL and surrounding parenchyma by fitting the reduced
      equation of the bicompartmental model to experimental data; t test, analysis of
      variance, and receiver operating characteristic analysis were performed. RESULTS:
      t Test showed significant differences in ADClesion, f lesion, D lesion, ADCratio,
      and D ratio values between benign and malignant FLLs, more pronounced for
      ADClesion (P < 0.0009) and ADCratio (P = 0.001). Applying cutoff values of 1.55 *
      10  mm/s (ADClesion) and 0.89 (ADCratio), the DwMR study presented sensitivities
      and specificities, respectively, of 84% and 80% (for ADClesion), 72% and 80%
      (ADCratio). CONCLUSIONS: Apparent diffusion coefficient (by fitting procedures)
      better performs than do D and f in FLL classification, especially when its values
      are less than 1.30 or greater than 2.00 * 10  mm/s.

PMID- 23863533
TI  - Discrepancy between preoperative imaging and surgical findings in patients with
      advanced ovarian cancer: a study of initial false-negative lesions.
AB  - OBJECTIVE: The objective of this study was to determine the patterns of erroneous
      interpretation of preoperative computed tomography (CT) for detection of
      peritoneal lesions in advanced ovarian cancer. METHODS: Between 2007 and 2011,
      148 patients with International Federation of Gynecology and Obstetrics stage
      IIIC-IV ovarian cancer, who underwent multi-detector-row CT before primary
      cytoreduction, were enrolled. We reviewed the preoperative CT and compared the
      findings with the surgical findings. For the discrepant cases, false-negative
      cases were reevaluated after revealing of surgical findings and were categorized
      as either absence or presence of lesion (missed case). We performed region-based
      comparisons according to predefined peritoneal lesion locations. RESULTS: Sixty
      eight false-negative cases were identified, of which 43 were revealed to be
      initially missed cases. The most common locations were found to be the small
      bowel mesentery (21%), subdiaphragmatic space (19%), and porta hepatis (16%).
      CONCLUSIONS: The missed peritoneal implants commonly resided in the same sites of
      preoperative imaging criteria that could predict suboptimal primary
      cytoreduction.

PMID- 23863534
TI  - Additional value of combined evaluation of tumor size with lymph node size in the
      detection of lymph node metastases in early-stage cervical cancer patients.
AB  - Although tumor size is a prognostic factor in cervical cancer patients, its role
      in the diagnosis of lymph node metastasis is unclear. We therefore evaluated the
      diagnostic value of tumor and lymph node size compared with lymph node size alone
      in the detection of metastatic lymph nodes in patients with early-stage cervical
      cancer.We retrospectively evaluated 699 patients with International Federation of
      Obstetrics and Gynecology stage IB1-IIA cervical carcinoma who underwent magnetic
      resonance imaging before lymphadenectomy involving all visible lymph nodes in the
      surgical fields. Seven nodal groups were evaluated: para-aortic, both common
      iliac, both external iliac, and both internal/obturator areas. Pathologic
      evaluation was the diagnostic standard. The largest short-axis diameter of lymph
      nodes in each region and the largest tumor diameters were measured in magnetic
      resonance images. The value of additional information from magnetic resonance
      images was evaluated by receiver operating characteristic curve analysis.Of the
      699 patients, 108 (15.8%) had lymph node metastases. The areas under the curve
      for measurements of lymph node size, tumor size, and both were (A) 0.635, (B)
      0.706, and (C) 0.742, respectively (A vs B, P = 0.006; A vs C P < 0.001; B vs C,
      P = 0.002).This study illustrates that magnetic resonance imaging measurements of
      tumor size and tumor size plus lymph node size showed a higher diagnostic
      performance than lymph node size alone in predicting lymph node metastasis in
      patients with early-stage cervical cancer. 

PMID- 23863535
TI  - Rapid assessment of liver volumetry by a novel automated segmentation algorithm.
AB  - OBJECTIVE: This study aimed to evaluate a novel segmentation software for
      automated liver volumetry and segmentation regarding segmentation speed and
      interobserver variability. METHODS: Computed tomographic scans of 20 patients
      without underlying liver disease and 10 patients with liver metastasis from
      colorectal cancer were analyzed by a novel segmentation software. Liver
      segmentation was performed after manual placement of specific landmarks into 9
      segments according to the Couinaud model as well as into 4 segments, the latter
      being import for surgery planning. Time for segmentation was measured and the
      obtained segmental and total liver volumes between the different readers were
      compared calculating intraclass correlations (ICCs). Volumes of liver tumor
      burden were evaluated similarly. RESULTS: Liver segmentation could be performed
      rapidly 3 minutes or less. Comparison of total liver volumes revealed a perfect
      ICC of greater than 0.997. Segmental liver volumes within the 9-part segmentation
      provided fair to moderate correlation for the left lobe and good to excellent
      correlations for the right lobe. When applying a 4-part segmentation relevant to
      clinical practice, strong to perfect agreement was observed. Similarly tumor
      volumes showed perfect ICC (>0.998). CONCLUSIONS: Rapid determination of total
      and segmental liver volumes can be obtained using a novel segmentation software
      suitable for daily clinical practice.

PMID- 23863536
TI  - Preoperative evaluation of lymphovascular invasion using high-resolution pelvic
      magnetic resonance in patients with rectal cancer: a 2-year follow-up study.
AB  - OBJECTIVES: The objectives of this study were to preoperatively evaluate
      lymphovascular invasion (LVI) using pelvic magnetic resonance (MR) in patients
      with rectal cancer and to determine the correlation with distant metastasis rate.
      METHODS: If the mesorectal perivascular infiltrative signal was visible on pelvic
      MR imaging, the possibility of LVI was recorded. Distant metastatic lesions were
      also recorded at the time of the initial diagnostic workup and over a 2-year
      follow-up period. RESULTS: Fifteen (68.2%) of the 22 LVI patients showed
      mesorectal perivascular infiltrative signals on pelvic MRI. For the prediction of
      LVI in rectal cancer, MR had a sensitivity of 68.2% and a specificity of 93.2.
      The initial distant metastasis rate was significantly higher in patients with MR
      LVI (52%) than in patients without MR LVI (5.7%) (P < 0.0001). CONCLUSIONS: On
      pelvic MR, the presence of mesorectal perivascular infiltration by nodes is a
      specific sign of LVI in rectal cancer, and the presence of LVI is a predictor of
      distant metastasis.

PMID- 23863537
TI  - Prostate volumetric assessment by magnetic resonance imaging and transrectal
      ultrasound: impact of variation in calculated prostate-specific antigen density
      on patient eligibility for active surveillance program.
AB  - OBJECTIVE: The objective of this study was to investigate impact of prostate
      volume variations on prostate-specific antigen density (PSAD) and patient
      eligibility for active surveillance (AS). METHODS: Prostate volume and PSAD were
      calculated for 46 patients with prostate cancer in AS who underwent prostate
      magnetic resonance imaging and transrectal ultrasound (TRUS). Manual method and 2
      semiautomated methods for prostate segmentation (3D-SLICER and OsiriX) were used
      for MR volumetry. RESULTS: Magnetic resonance volumetric methods showed very good
      agreement (intraclass correlation coefficient, 0.98). The concordance correlation
      coefficient was higher among MR volumetry methods (0.971-0.998) than between TRUS
      and MR volumetry (0.849-0.863). The variation in PSAD estimated by TRUS versus
      magnetic resonance imaging was higher in large prostates (r = 0.327, P = 0.027).
      Transrectal ultrasonography volumetry may improperly classify 20% of patients as
      eligible for AS with PSAD greater than 0.15 threshold. CONCLUSIONS: Although
      clinically used TRUS reliably estimates PSAD, it may misclassify some patients
      who are not eligible for AS based on PSAD criteria. Magnetic resonance-based
      volumetry should be considered for a more reliable PSAD calculation.

PMID- 23863538
TI  - (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography
      findings are different between invasive and noninvasive pulmonary aspergillosis.
AB  - OBJECTIVE: Invasive pulmonary aspergillosis (IPA) is a significant cause of
      morbidity and mortality especially in immunocompromised patients, and extensive
      work has been done in the field of diagnostic imaging. The purpose of our study
      was to evaluate functional metabolic image findings of F-fluoro-2-deoxy-D-glucose
      (FDG) positron emission tomography (PET)/computed tomography (CT) in the patients
      with invasive and noninvasive forms of pulmonary aspergillosis (IPA and NIPA,
      respectively). METHODS: We retrospectively reviewed 24 consecutive patients who
      had pulmonary aspergillosis among the patients who underwent F-FDG PET/CT to
      evaluate lung mass or fever of unknown origin. Demographic feature, multiplicity,
      visually analyzed F-FDG uptake patterns (isometabolic halo, isometabolic nodule,
      hypermetabolic nodule, or other), and the peak standardized uptake value
      (SUVpeak) of the pulmonary lesions on PET/CT were evaluated. RESULTS: Of these 24
      patients, 8 were diagnosed with IPA and 16 with NIPA. Patients with IPA were
      significantly younger (48 vs 62 years), and immunocompromised conditions were
      more frequently observed in these cases (88% vs 6%). Multiple lesions were noted
      in 50% (4 of 8) and 19% (3 of 16) of IPA and NIPA patients, respectively, and the
      predominant patterns on F-FDG PET/CT were the hypermetabolic nodule pattern (6 of
      8 patients, 75%) and the isometabolic halo pattern (8 of 16 patients, 50%) in IPA
      and NIPA patients, respectively. The isometabolic halo pattern was not observed
      in IPA patients. The median SUVpeak was 4.5 (range, 1.3-8.9) and 1.6 (range, 0.5
      3.1) in IPA and NIPA, respectively. CONCLUSIONS: F-FDG PET/CT findings differ
      between IPA and NIPA patients. Pulmonary aspergillosis in immunocompromised
      status with a hypermetabolic nodule pattern on F-FDG PET/CT seems to have high
      possibility of IPA. In contrast, an isometabolic halo pattern and an isometabolic
      nodule pattern on F-FDG PET/CT seem to have high possibility of NIPA.

PMID- 23863540
TI  - Low-dose chest computed tomography with sinogram-affirmed iterative
      reconstruction, iterative reconstruction in image space, and filtered back
      projection: studies on image quality.
AB  - OBJECTIVE: This study aimed to determine optimal strength of sinogram-affirmed
      iterative reconstruction (SAFIRE) and to evaluate image quality (IQ) of low-dose
      chest computed tomography (LDCT) using SAFIRE compared with iterative
      reconstruction in image space (IRIS) and filtered back projection (FBP). METHODS:
      Thirty patients underwent LDCT. Computed tomography (CT) was reconstructed using
      5 strengths of SAFIRE (S1-S5), IRIS, and FBP. Objective noise of CT was measured.
      Two radiologists evaluated CT for subjective IQ, beam-hardening artifacts, and
      overall IQ. RESULTS: Measured noise was highest in FBP, followed by S1, S2, S3,
      IRIS, S4, and S5. S2 and S3 demonstrated significantly higher overall IQ scores
      than the other strengths (P < 0.05). Overall IQ and beam-hardening artifacts of
      S2 and S3 were significantly better than those in FBP and IRIS (P < 0.001).
      CONCLUSIONS: S2 or S3 strengths of SAFIRE can be used practically in clinical
      routines and may have more potential than IRIS and FBP for LDCT with improved IQ.

PMID- 23863539
TI  - Computed tomography findings in septic patients with acute respiratory distress
      syndrome: correlation with survival and pulmonary versus extrapulmonary septic
      focus.
AB  - OBJECTIVE: The objective of this study was to evaluate computed tomography (CT)
      findings in patients with sepsis with unknown inflammatory focus and acute
      respiratory distress syndrome. METHODS: Acute respiratory distress syndrome
      findings on CT of 36 patients with sepsis were graded on a 6-point scale, and the
      percentage of affected lung was estimated. Resulting CT scores were correlated to
      intensive care scores and survival. RESULTS: Forty-four percent of the patients
      died, revealing a significantly higher CT score than survivors (P = 0.01).
      Survivors showed larger areas of unaffected lung (P < 0.001), whereas patients
      with fatal outcome had more ground-glass opacities (P = 0.002; sensitivity, 73%;
      specificity, 57%) and traction bronchiectasis (P = 0.009; sensitivity, 54%;
      specificity, 68%). Pulmonary findings on CT did not allow discriminating between
      a pulmonary and extrapulmonary focus. No significant coherence between CT score
      and intensive care scores could be revealed. CONCLUSIONS: A CT scoring system
      based on pulmonary findings in patients with sepsis with acute respiratory
      distress syndrome comprises prognostic implications in terms of the patients'
      survival.

PMID- 23863541
TI  - Low-contrast agent dose dual-energy CT monochromatic imaging in pulmonary
      angiography versus routine CT.
AB  - OBJECTIVE: This study aimed to retrospectively evaluate the feasibility and
      reliability of low-contrast agent dose dual-energy computed tomography (DECT)
      monochromatic imaging in pulmonary angiography. METHODS: Computed tomography
      pulmonary angiography was performed in 86 patients, 41 in 120-kVp computed
      tomography (CT) and 45 in DECT with low-contrast agent dose. The images in DECT
      were reconstructed at optimal kiloelectron-voltage (keV), demonstrating the best
      contrast-to-noise ratio between pulmonary artery and soft tissue, and at 70 keV.
      Image quality was compared by quantitative and subjective indexes. The radiation
      doses were recorded. RESULTS: Compared with 120-kVp CT, optimal keV showed
      superior quantitative indexes with inferior subjective image quality, whereas 70
      keV demonstrated no statistical difference in quantitative indexes with superior
      subjective image quality. All suspicious pulmonary embolisms in DECT were
      diagnosed confidently by combination of 2 kinds of monochromatic imaging. The
      radiation dose in DECT is almost twice as 120-kVp CT. CONCLUSIONS: Low-contrast
      agent dose DECT monochromatic imaging in pulmonary angiography accommodates
      superior intravascular enhancement and contrast in pulmonary arteries, and
      improves diagnostic confidence with compatible radiation dose.

PMID- 23863542
TI  - Low-dose computed tomography (LDCT) in workers previously exposed to asbestos:
      detection of parenchymal lung disease.
AB  - OBJECTIVES: To evaluate the lungs of asymptomatic asbestos-exposed workers who
      were screened for lung cancer and mesothelioma using low-dose computed tomography
      (LDCT) for parenchymal abnormalities. METHODS: Three hundred fifteen baseline
      LDCT studies of the chest of participants with at least 20 years' exposure to
      asbestos or presence of pleural plaques before enrollment on chest radiographs
      were analyzed. RESULTS: Three hundred fifteen subjects were studied. The mean age
      was 61.7 years, and the mean exposure to asbestos was 26.9 years. One hundred
      seventy-five (56%) participants had absence of parenchymal findings with a mean
      age of 58.7 years, mean exposure of 24.6 years, and a mean smoking pack years of
      19. One hundred forty subjects (44%) had parenchymal findings (138 men and 2
      women) with a mean age of 65.3 years, mean exposure of 29.73 years, and a mean
      smoking pack years of 21.5 years. Participants who had parenchymal manifestations
      were more likely to be older and have longer exposure to asbestos compared to
      participants who had no relevant parenchymal findings. There was no statistical
      difference in the mean smoking pack years between the groups with and without
      parenchymal findings. CONCLUSIONS: Low-dose CT could demonstrate parenchymal lung
      manifestations in this higher-risk asymptomatic group with prior exposure to
      asbestos in the setting of screening for lung cancer and mesothelioma.
      Individuals with longer exposure to asbestos and of higher age have more
      pulmonary abnormalities. The age and the latency of exposure play an important
      role given that the asbestos-related parenchymal abnormalities on LDCT were more
      prevalent in the elderly participants and with longer periods of exposure.

PMID- 23863543
TI  - Morphology of large rotator cuff tears and of the rotator cable and long-term
      shoulder disability in conservatively treated elderly patients.
AB  - OBJECTIVE: The objective of this study was to describe the morphology of the
      rotator cuff tendon tears and long-term shoulder disability in conservatively
      treated elderly patients and determine if an association exists between these
      factors. METHODS: Assessment of the rotator cuff tendon tear dimensions and
      depth, rotator interval involvement, rotator cable morphology and location, and
      rotator cuff muscle status was carried out on magnetic resonance studies of 24
      elderly patients treated nonoperatively for rotator cuff tendon tears. Long-term
      shoulder function was measured using the Western Ontario Rotator Cuff (WORC)
      index; Disabilities of the Shoulder, Arm, and Hand questionnaire; and the
      American Shoulder Elbow Self-assessment form, and a correlation between the
      outcome scores and morphologic magnetic resonance findings was carried out.
      RESULTS: The majority of large rotator cuff tendon tears are limited to the
      rotator cuff crescent. Medial rotator interval involvement (isolated or in
      association with lateral rotator interval involvement) was significantly
      associated with WORC physical symptoms total (P = 0.01), WORC lifestyle total (P
      = 0.04), percentage of all WORC domains (P = 0.03), and American Shoulder Elbow
      Self-assessment total (P = 0.01), with medial rotator interval involvement
      associated with an inferior outcome. CONCLUSIONS: Medial rotator interval tears
      are associated with long-term inferior outcome scores in conservatively treated
      elderly patients with large rotator cuff tendon tears.

PMID- 23863544
TI  - Four-dimensional computed tomography and trigger lunate syndrome.
AB  - BACKGROUND: A 22-year-old man with no history of trauma and normal plain films,
      ultrasound, and magnetic resonance imaging presents with several months of
      increasingly severe pain and clicking in the right wrist. He is clinically
      diagnosed with midcarpal instability and undergoes a 4-dimensional computed
      tomography scan of his wrist for further evaluation. METHODS: The motion of the
      subject's lunate was evaluated through a full arc of flexion and extension as
      well as radial and ulnar deviation. A comparison was made with the lunate of an
      asymptomatic patient demonstrating the same motions. RESULTS: The symptomatic
      lunate demonstrated early smooth motion, followed by cessation of motion, and
      then again followed by smooth catch up motion. The asymptomatic patient
      demonstrated smooth lunate motion throughout the study. DISCUSSION: The lunate
      motion, with an abrupt cessation and recommencement of flexion/extension, was
      consistent with a triggering phenomenon. This trigger lunate motion abnormality,
      although consistent with the "clunking" sensation often described during the
      physical examination, has not been previously recognized radiographically as a
      feature of midcarpal instability.

PMID- 23863545
TI  - Prevalence of nausea and vomiting of pregnancy in the USA: a meta analysis.
AB  - BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical
      condition during gestation, carrying tremendous health burden, especially for the
      severe form, hyperemesis gravidarum (HG). The rates of NVP in the USA have not
      been systematically calculated. OBJECTIVES: To estimate the rates of NVP and HG
      in the USA. METHODS: A meta-analysis was conducted of all peer-reviewed articles
      from the USA that provided rates of NVP in early or late pregnancy or HG.
      Medline, Embase and Cochrane databases were searched from inception through
      November 2012; reviews and articles were hand searched. Rates were combined
      across studies using a random effects model. RESULTS: Forty-eight articles were
      identified; 15 were rejected and 33 were included for analysis. Twenty-three
      studies of 67,602 women provided rates of NVP which had a meta-analytic rate of
      68.6% (CI95%:64.4%-72.8%). Three of them (N=5034) reported nausea without
      vomiting in 28.6% and two studies (N=136) produced a rate for NVP during late
      pregnancy of 24.0%. HG occurred in 1.2% of the 2.1 million women in 12 studies.
      CONCLUSIONS: We have summarized rates of NVP and HG, which are similar to those
      found in other parts of the world. Almost 70% of women suffer some form of the
      syndrome; 1.2% have the severe form, most of whom were hospitalized because of
      the HG. Future research should address issues of cost and resource utilization.

PMID- 23863546
TI  - Mathematical models to assess foot-ground interaction: an overview.
AB  - The mechanical properties of the interface between the human body and the ground
      play an important role in attenuating the foot strike impact during locomotion.
      Understanding the properties of such an impact-attenuating system and the
      mathematical models governing its behavior has major implications in determining
      the load on the musculoskeletal system during locomotion. This interface consists
      of the plantar soft tissue and the sole complex of the shoe that together act
      like a sophisticated suspension system with generic viscoelastic properties. The
      interface has generally been modeled as a system of spring and damper, in which
      the reaction force deformation is expressed by a mathematical equation that
      represents the reaction force as a nonlinear function of the deformation and
      deformation rate of the interface. This overview intends to provide an insight
      into the different mathematical models that have been used to describe such
      relationship and into further understanding the role of the reaction model
      parameters in determining the behavior of the interface under compression.
      Various models included within this review ranged from the models representing
      the plantar soft tissue behavior during barefoot walking to those that consider
      the sole complex force-deformation behavior during shod foot running. The
      barefoot models are categorized under in vitro/in situ and in vivo, whereas the
      models representing the sole complex behavior are investigated before discussing
      the shod foot models. The mathematical models varied from those in which the
      reaction force was a nonlinear function of interface deformation to those that
      considered the deformation rate of the interface as a contributing factor to the
      interface reaction force. Ultimately, the implication of the reaction models in
      determining the load on the musculoskeletal system is discussed. 

PMID- 23863547
TI  - Validation of a previous-day recall measure of active and sedentary behaviors.
AB  - PURPOSE: A previous-day recall (PDR) may be a less error-prone alternative to
      traditional questionnaire-based estimates of physical activity and sedentary
      behavior (e.g., past year), but the validity of the method is not established. We
      evaluated the validity of an interviewer administered PDR in adolescents (12-17
      yr) and adults (18-71 yr). METHODS: In a 7-d study, participants completed three
      PDR, wore two activity monitors, and completed measures of social desirability
      and body mass index. PDR measures of active and sedentary time was contrasted
      against an accelerometer (ActiGraph) by comparing both to a valid reference
      measure (activPAL) using measurement error modeling and traditional validation
      approaches. RESULTS: Age- and sex-specific mixed models comparing PDR to activPAL
      indicated the following: 1) there was a strong linear relationship between
      measures for sedentary (regression slope, beta1 = 0.80-1.13) and active time
      (beta1 = 0.64-1.09), 2) person-specific bias was lower than random error, and 3)
      correlations were high (sedentary: r = 0.60-0.81; active: r = 0.52-0.80).
      Reporting errors were not associated with body mass index or social desirability.
      Models comparing ActiGraph to activPAL indicated the following: 1) there was a
      weaker linear relationship between measures for sedentary (beta1 = 0.63-0.73) and
      active time (beta1 = 0.61-0.72), (2) person-specific bias was slightly larger
      than random error, and (3) correlations were high (sedentary: r = 0.68-0.77;
      active: r = 0.57-0.79). CONCLUSIONS: Correlations between the PDR and the
      activPAL were high, systematic reporting errors were low, and the validity of the
      PDR was comparable with the ActiGraph. PDR may have value in studies of physical
      activity and health, particularly those interested in measuring the specific
      type, location, and purpose of activity-related behaviors.

PMID- 23863548
TI  - Diagnostic utility of p63 expression in the differential diagnosis of pagetoid
      squamous cell carcinoma in situ and extramammary Paget disease: a histopathologic
      study of 70 cases.
AB  - Pagetoid squamous cell carcinoma in situ (PSCCIS) is characterized by
      cytologically atypical cells, with abundant, pale-staining cytoplasm arranged
      singly and in nests within the epidermis (pagetoid distribution). The growth
      pattern of PSCCIS may simulate extramammary Paget disease (EMPD), and in some
      cases, it is difficult to differentiate the 2 entities based on histomorphology
      alone. In this study, biopsy samples from 30 cases of PSCCIS and 40 cases of
      primary EMPD were examined using immunohistochemical staining for p63. In cases
      where the boundaries between the pagetoid cells and surrounding keratinocytes
      were difficult to assess, an eosin counterstain was applied to highlight the
      cytoplasm of the lesional cells. The immunohistochemical results were analyzed
      using Fisher exact test. The results showed that all 30 cases of PSCCIS exhibited
      strong nuclear positivity for p63 in the neoplastic cells, when compared with 0
      of 40 cases of primary EMPD (P < 0.0001). In summary, p63 is a useful marker in
      differentiating PSCCIS from primary EMPD. The authors propose the addition of p63
      immunostain in the panel of markers when evaluating pagetoid cutaneous neoplasms.

PMID- 23863549
TI  - Localized cutaneous argyria: two case reports and clinicopathologic review.
AB  - We report 2 cases of patients who presented with blue macules clinically
      suspicious for blue nevi. One patient had no documented history of trauma or
      silver exposure, and the other reported exposure to silver over 30 years ago.
      Microscopic examination revealed a dermal population of brown-black globules
      predominantly adhering to collagen fibers. In both cases, no melanocytic
      proliferation was identified by immunohistochemistry. Analysis of the skin
      biopsies with scanning electron microscopy and energy dispersive x-ray
      spectroscopy demonstrated the presence of silver and selenium. These findings
      were diagnostic of localized cutaneous argyria. Our case reports highlight the
      importance of including localized cutaneous argyria in the differential diagnosis
      of pigmented lesions.

PMID- 23863550
TI  - Case report: differential diagnosis between primary cutaneous apocrine
      adenocarcinoma versus extramammary or metastatic breast adenocarcinoma.
AB  - Cutaneous apocrine adenocarcinoma (CAA) is a rare adnexal neoplasm that
      histologically can mimic breast carcinoma metastatic to the skin or apocrine
      carcinoma arising in ectopic breast tissue. It can present with a wide range of
      clinical modalities and can often simulate many benign processes, which delays
      its diagnosis and hinders its prognosis. We describe a case of a 33-year-old man
      who had a short-evolution small nodule in the right axilla with local lymph node
      metastases. The immunohistochemical characterization was closer to that of breast
      adenocarcinoma than to an adnexal neoplasm. This was established as the main
      differential diagnosis. Diagnosis of cutaneous apocrine adenocarcinoma may be
      difficult and immunomarkers are not specific. The anatomical criteria and
      systemic investigation are mandatory to establish the correct diagnosis.

PMID- 23863551
TI  - Angioinvasive lymphomatoid papulosis: another case of a newly described variant.
AB  - Lymphomatoid papulosis (LyP) is a chronic recurrent lymphoproliferative disorder
      characterized clinically by self-regressing cutaneous lesions. Histologically, it
      is recognized by clusters of CD30 atypical lymphocytes in the background of mixed
      inflammatory infiltrate. It has been classified as type A, B, C, and D. Recently,
      a further variant of LyP was described as "angioinvasive LyP" in a series of 16
      patients. We report a case of a 73-year-old female presenting with papules and
      nodules on the extremities evolving into eschar-like necrotic plaques.
      Histological examination revealed medium- to large-sized atypical lymphoid CD30
      cells densely infiltrating the dermis with distinct angioinvasion and
      angiodestruction. No systemic involvement was identified. The clinicopathologic
      features conformed to the newly described angioinvasive LyP.

PMID- 23863553
TI  - Acantholysis in mammary Paget disease.

PMID- 23863552
TI  - Rosai-Dorfman disease: a case report with nodal and cutaneous involvement and
      review of the literature.
AB  - Rosai-Dorfman disease, also known as sinus histiocytosis with massive
      lymphadenopathy, is a benign proliferative disorder of histiocytes with an
      unknown etiology. It is a rare disease characterized by overproduction and
      accumulation of histiocytes within lymph node sinuses and many other extranodal
      sites, including skin, oral and nasal cavities, respiratory tract, eyelid, and
      periorbital area. In this case, a 44-year-old woman with diagnosis of Rosai
      Dorfman disease, with xanthelasma-like cutaneous lesions on facial area,
      extending to her neck and acneiform papules on her back, cervical lymph node
      involvement, and concomitant presence of diabetes insipidus was presented.
      Histopathological examination of the lesions demonstrated diffuse lymphocyte,
      plasmocyte, eosinophil, and sparse neutrophil infiltration, together with
      histiocytes showing phagocytosed inflammatory cells (emperipolesis). Histiocytes
      demonstrated immunoreactivity with the antibodies for CD68 and S100, whereas they
      were negative for CD1a and Langerin. Laboratory tests were normal, except mild
      immunoglobulin G hypergammaglobulinemia. Systemic methylprednisolone therapy was
      effective for cutaneous lesions.

PMID- 23863554
TI  - Merkel cell carcinoma exhibiting cytoplasmic OCT4 staining: a potential new
      diagnostic immunohistochemical marker.

PMID- 23863555
TI  - Intraoral scanners have arrived.

PMID- 23863556
TI  - Upper-incisor root control with Invisalign appliances.

PMID- 23863557
TI  - A chairside customized chin cup.

PMID- 23863558
TI  - Practical and esthetic considerations in adult canine-extraction treatment.

PMID- 23863559
TI  - The efficacy of enamel sandblasting in bonding to fluorosed teeth.

PMID- 23863560
TI  - Management of unilateral condylar hyperplasia with a high condylectomy, skeletal
      anchorage, and a CAD/CAM alloplast.

PMID- 23863561
TI  - A bone-borne appliance for rapid maxillary expansion.

PMID- 23863562
TI  - Nasopharyngeal carcinoma incidence and mortality in China in 2009.
AB  - Nasopharyngeal carcinoma (NPC) is rare globally but common in China and exhibits
      a distinct ethnic and geographic distribution. In 2009, the National Central
      Cancer Registry in China provided real-time surveillance information on NPC.
      Individual NPC cases were retrieved from the national database based on the ICD
      10 topography code C11. The crude incidence and mortality of NPC were calculated
      by sex and location (urban/rural). China's population in 1982 and Segi's world
      population structures were used to determine age-standardized rates. In regions
      covered by the cancer registries in 2009, the crude incidence of NPC was
      3.61/100,000 (5.08/100,000 in males and 2.10/100,000 in females; 4.19/100,000 in
      urban areas and 2.42/100,000 in rural areas). Age-standardized incidences by
      Chinese population (ASIC) and Segi's world population (ASIW) were 2.05/100,000
      and 2.54/100,000, respectively. The crude mortality of NPC was 1.99/100,000
      (2.82/100,000 in males and 1.14/100,000 in females; 2.30/100,000 in urban areas
      and 1.37/100,000 in rural areas). The age-standardized mortalities by Chinese
      population (ASMC) and world population (ASMW) were 1.04/100,000 and 1.35/100,000,
      respectively. The incidence and mortality of NPC were higher in males than in
      females and higher in urban areas than in rural areas. Both age-specific
      incidence and mortality were relatively low in persons younger than 30 years old,
      but these rates dramatically increased. Incidence peaked in the 60-64 age group
      and mortality peaked in the over 85 age group. Primary and secondary prevention,
      such as lifestyle changes and early detection, should be carried out in males and
      females older than 30 years of age.

PMID- 23863563
TI  - Comparison of the Xpert MTB/RIF and Cobas TaqMan MTB assays for detection of
      Mycobacterium tuberculosis in respiratory specimens.
AB  - The Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA) is a fully automated, cartridge
      based real-time PCR assay designed to detect Mycobacterium tuberculosis and
      rifampin resistance within 2 h. The performance of the Xpert assay has been
      evaluated in various clinical settings. However, there are few data comparing the
      Xpert assay to the Cobas TaqMan MTB test (Roche Diagnostics, Basel, Switzerland),
      one of the most widely utilized molecular assays for M. tuberculosis detection.
      In this prospective study, 320 consecutive respiratory specimens were processed
      simultaneously using acid-fast bacillus (AFB) staining, mycobacterial cultures
      with both solid and liquid media, and the Cobas and Xpert assays. The Xpert assay
      was performed with direct respiratory specimens, while the Cobas assay was done
      with decontaminated concentrated specimens. Based on the culture as a reference
      method, the overall sensitivities of the Cobas and Xpert assays were 71.4% and
      67.9%, respectively. When AFB smear results were taken into consideration, the
      sensitivities of the Cobas assay for smear-positive and -negative specimens were
      87% and 54%, while those of the Xpert assay were 67% and 69%, respectively. The
      Cobas assay showed 100% specificity and 100% positive predictive value (PPV)
      regardless of smear results, while the Xpert assay showed 100% specificity and
      100% PPV for smear-positive specimens but 98% specificity and 60% PPV for smear
      negative specimens. In conclusion, the Xpert assay showed performance that was
      slightly inferior to that of the Cobas assay but seems useful for the rapid
      detection of M. tuberculosis, considering that it was performed without laborious
      and time-consuming decontamination and concentration procedures. 

PMID- 23863564
TI  - Evaluation of the BD Bactec MGIT 320 system for detection of mycobacteria and
      drug susceptibility testing of Mycobacterium tuberculosis.
AB  - Two different laboratories evaluated growth and detection of mycobacteria and
      drug susceptibility testing of Mycobacterium tuberculosis by the BD Bactec MGIT
      320 using the BD Bactec MGIT 960 (BD Diagnostics, Sparks, MD) as a reference
      method. Out of 359 processed sputum specimens for detection of mycobacteria,
      99.7% were in agreement between the MGIT 320 and MGIT 960. Streptomycin (STR),
      isoniazid (INH), rifampin (RIF), ethambutol (EMB) (collectively known as SIRE),
      and pyrazinamide (PZA) drug susceptibility testing was performed on 89 clinical
      strains, prepared from both liquid and solid inocula. The results of SIRE and PZA
      were 100% reproducible between the two instruments tested at both laboratories. 

PMID- 23863565
TI  - Parametrial anisakidosis.
AB  - Anisakidosis is a parasitic infection caused by anisakid nematodes in the genera
      Anisakis and Pseudoterranova. Infection is not uncommon in the United States due
      to increased raw seafood consumption. We report the first known case of
      parametrial anisakidosis in a 42-year-old woman and review existing literature. 

PMID- 23863566
TI  - Methylation of human papillomavirus Type 16 CpG sites at E2-binding site 1
      (E2BS1), E2BS2, and the Sp1-binding site in cervical cancer samples as determined
      by high-resolution melting analysis-PCR.
AB  - High-risk (HR) human papillomavirus (HPV)-associated carcinogenesis is driven
      mainly by the overexpression of E7 and E6 oncoproteins following viral DNA
      integration and the concomitant loss of the E2 open reading frame (ORF). However,
      the integration of HR-HPV DNA is not systematically observed in cervical cancers.
      The E2 protein acts as a transcription factor that governs viral oncogene
      expression. The methylation of CpGs in the E2-binding sites (E2BSs) in the viral
      long control region abrogates E2 binding, thus impairing the E2-mediated
      regulation of E7/E6 transcription. Here, high-resolution melting (HRM)-PCR was
      developed to quantitatively analyze the methylation statuses of E2BS1, E2BS2, and
      the specificity protein 1 (Sp1)-binding site in 119 HPV16-positive cervical
      smears. This is a rapid assay that is suitable for the analysis of cervical
      samples. The proportion of cancer samples with methylated E2BS1, E2BS2, and Sp1
      binding site CpGs was 47%, whereas the vast majority of samples diagnosed as
      being within normal limits, low-grade squamous intraepithelial lesions (LSIL), or
      high-grade squamous intraepithelial lesions (HSIL) harbored unmethylated CpGs.
      Methylation levels varied widely, since some cancer samples harbored up to 60% of
      methylated HPV16 genomes. A pyrosequencing approach was used as a confirmation
      test and highlighted that quantitative measurement of methylation can be achieved
      by HRM-PCR. Its prognostic value deserves to be investigated alone or in
      association with other biomarkers. The reliability of this single-tube assay
      offers great opportunities for the investigation of HPV16 methylation in other
      HPV-related cancers, such as head and neck cancers, which are a major public
      health burden. 

PMID- 23863568
TI  - Invasive fungal infection due to Triadelphia pulvinata in a patient with acute
      myeloid leukemia.
AB  - Triadelphia pulvinata is a rare dematiaceous fungus found in soil. We report the
      first case of invasive disease in a patient with acute myeloid leukemia who had a
      bloodstream infection with possibly both lung and brain involvement.
      Identification was by combined phenotypic features and fungal ribosomal DNA
      sequence analysis. 

PMID- 23863567
TI  - Description of an unusual Neisseria meningitidis isolate containing and
      expressing Neisseria gonorrhoeae-Specific 16S rRNA gene sequences.
AB  - An apparently rare Neisseria meningitidis isolate containing one copy of a
      Neisseria gonorrhoeae 16S rRNA gene is described herein. This isolate was
      identified as N. meningitidis by biochemical identification methods but generated
      a positive signal with Gen-Probe Aptima assays for the detection of Neisseria
      gonorrhoeae. Direct 16S rRNA gene sequencing of the purified isolate revealed
      mixed bases in signature regions that allow for discrimination between N.
      meningitidis and N. gonorrhoeae. The mixed bases were resolved by sequencing
      individually PCR-amplified single copies of the genomic 16S rRNA gene. A total of
      121 discrete sequences were obtained; 92 (76%) were N. meningitidis sequences,
      and 29 (24%) were N. gonorrhoeae sequences. Based on the ratio of species
      specific sequences, the N. meningitidis strain seems to have replaced one of its
      four intrinsic 16S rRNA genes with the gonococcal gene. Fluorescence in situ
      hybridization (FISH) probes specific for meningococcal and gonococcal rRNA were
      used to demonstrate the expression of the rRNA genes. Interestingly, the clinical
      isolate described here expresses both N. meningitidis and N. gonorrhoeae 16S rRNA
      genes, as shown by positive FISH signals with both probes. This explains why the
      probes for N. gonorrhoeae in the Gen-Probe Aptima assays cross-react with this N.
      meningitidis isolate. The N. meningitidis isolate described must have obtained N.
      gonorrhoeae-specific DNA through interspecies recombination. 

PMID- 23863569
TI  - Comparison of Xpert MRSA/SA Nasal and MRSA/SA ELITe MGB assays for detection of
      the mecA gene with susceptibility testing methods for determination of
      methicillin resistance in Staphylococcus aureus isolates.
AB  - In a series of 82 Staphylococcus strains isolated from culture, 100% were
      identified as Staphylococcus aureus by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS); 99.9% (77/82) of them
      were resistant to benzylpenicillin, oxacillin, and cefoxitin, and 6.1% (5/82)
      were susceptible to methicillin. Xpert MRSA/SA assay results were concordant with
      the phenotypic results in 76.8% (63/82) of cases and discordant in 23.2% (19/82)
      of cases. The MRSA/SA ELITe MGB kit results were concordant with phenotypic
      results in 100% of the cases. When comparing the Xpert MRSA/SA assay results with
      the MRSA/SA ELITe MGB kit results, 78% (64/82) of the cases were concordant,
      while 22% (18/82) of the cases were discordant. No statistically significant
      differences were observed between the two techniques. The PCR protocol that was
      used to validate the results of these two methods gave the following results: 49
      were conventional methicillin-resistant S. aureus (MRSA) isolates (mecA positive
      and mecALGA251 negative), and 25 were phenotypic MRSA isolates (mecA negative and
      mecALGA251 positive). 

PMID- 23863570
TI  - Novel method based on "en passant" mutagenesis coupled with a gaussia luciferase
      reporter assay for studying the combined effects of human cytomegalovirus
      mutations.
AB  - Human cytomegalovirus (HCMV) resistance to antivirals is a major problem in
      immunocompromised patients. Drug resistance is characterized by phenotypic
      testing or genotypic analysis of the phosphotransferase (UL97) and DNA polymerase
      (UL54) genes. However, genotypic assays require further characterization of
      unknown mutations in the drug resistance phenotype. Here, we describe a novel
      method for generating single or multiple mutations anywhere in the HCMV genome
      and for studying their effects on drug susceptibility. This method is based on
      cloning of the reference AD169 strain in a bacterial artificial chromosome and
      the use of "en passant" mutagenesis in bacteria to introduce mutations in
      recombinant HCMV without scar sequences. We also used this methodology to
      introduce the Gaussia luciferase reporter gene into the genome of the recombinant
      virus. To validate our system, the well-characterized single mutants with UL97
      A594V and UL54 E756K mutations as well as the undescribed A594V/E756K double
      mutant were generated and their drug susceptibility profiles were determined by
      measuring the luciferase activity in cell culture supernatants. Drug
      susceptibility phenotypes for the A594V (8.2-fold increase in ganciclovir 50%
      effective concentration [EC50]) and E756K (1.9-, 3.9-, and 3.0-fold increases in
      ganciclovir, foscarnet, and cidofovir EC50s, respectively) mutants were similar
      to those previously reported, while the double mutant exhibited 10.8-, 4.1-, and
      2.0-fold increases in ganciclovir, foscarnet, and cidofovir EC50s, respectively.
      The combination of the Gaussia luciferase reporter-based assay with the
      markerless "en passant" mutagenesis methodology constitutes an efficient system
      for studying phenotypes with single or multiple HCMV mutations. 

PMID- 23863571
TI  - UV-fixed-thick-blotch preparation improves sensitivity of auramine staining.
AB  - We describe here a very simple modification of the auramine staining procedure
      based on preparation of a UV-fixed thick blotch which allowed us to reach an
      overall sensitivity of 0.82 (592 acid-fast bacillus [AFB]-positive specimens/722
      initial respiratory specimens with positive mycobacterial culture) and
      sensitivities of 0.93 (526 AFB-positive specimens/564 culture-positive specimens)
      for Mycobacterium tuberculosis complex and 0.42 (66 AFB-positive specimens/158
      culture-positive specimens) for nontuberculous mycobacteria. 

PMID- 23863572
TI  - Isolation and characterization of small-colony variants of Ornithobacterium
      rhinotracheale.
AB  - Ornithobacterium rhinotracheale is a Gram-negative bacterium associated with
      respiratory diseases in many avian species, with worldwide distribution, and it
      causes significant economic loss to the poultry industry. In this study, the
      isolation and characterization of O. rhinotracheale small-colony variants (SCVs)
      are described for the first time. O. rhinotracheale isolates (n = 27) were
      recovered from tracheal samples (n = 321) collected from different avian species
      with clinical signs of respiratory disease. Of the 27 O. rhinotracheale isolates,
      21 (77.8%) showed SCVs in their primary cultures. Five O. rhinotracheale SCV
      isolates showed high levels of stability and were chosen for further
      characterization with their wild-type (WT) isolates. Stable O. rhinotracheale
      SCVs were oxidase negative, while their WT isolates were positive. Growth curves
      for stable O. rhinotracheale SCVs indicated lower growth rates and longer lag
      phases than for their WT isolates. Furthermore, it was possible to increase the
      efficacy of the broth medium in supporting the growth of O. rhinotracheale WT
      isolates by supplementing it with 5% fetal bovine serum (FBS) and 2% IsoVitaleX
      Enrichment. Antibiotic susceptibility tests showed that O. rhinotracheale SCVs
      had higher MIC values than their WT isolates. This study suggests that successful
      antibiotic treatment of respiratory diseases associated with O. rhinotracheale
      must take into consideration the resistance patterns of O. rhinotracheale SCVs.
      Intracellular persistence in murine RAW 264.7 macrophages revealed that O.
      rhinotracheale SCV28 had higher survival rates than its WT isolate. Finally,
      small-colony variants may be important contributors to the pathogenesis of O.
      rhinotracheale. 

PMID- 23863573
TI  - High Coxiella burnetii DNA load in serum during acute Q fever is associated with
      progression to a serologic profile indicative of chronic Q fever.
AB  - PCR is very effective in diagnosing acute Q fever in the early stages of
      infection, when bacterial DNA is present in the bloodstream but antibodies have
      not yet developed. The objective of this study was to further analyze the
      diagnostic value of semiquantitative real-time PCR (qPCR) in diagnosing acute Q
      fever in an outbreak situation. At the Jeroen Bosch Hospital, in 2009, qPCR
      testing for Coxiella burnetii DNA was performed for 2,715 patients suspected of
      having acute Q fever (positive, n = 385; negative, n = 2,330). The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of the qPCR assay were calculated for patients with negative qPCR results with a
      follow-up sample obtained within 14 days (n = 305) and qPCR-positive patients
      with at least one follow-up sample (n = 369). The correctness of the qPCR result
      was based on immunofluorescence assay results for samples submitted for qPCR and
      follow-up testing. The sensitivity of the Q fever qPCR assay was 92.2%,
      specificity 98.9%, PPV 99.2%, and NPV 89.8%. Patients who later developed
      serologic profiles indicative of chronic Q fever infection had significantly
      higher C. burnetii DNA loads during the acute phase than did patients who did not
      (P < 0.001). qPCR testing is a valuable tool for the diagnosis of acute Q fever
      and should be used in outbreak situations when the onset of symptoms is <15 days
      earlier. Special attention is needed in the follow-up monitoring of patients with
      high C. burnetii DNA loads during the acute phase, as this might be an indicator
      for the development of a serologic profile indicative of chronic infection. 

PMID- 23863575
TI  - Quantifying the global rates of nausea and vomiting of pregnancy: a meta
      analysis.
AB  - BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical
      condition in pregnancy, affecting women worldwide. It is unclear whether its
      prevalence and severity NVP are variable across different nations and races.
      PURPOSE: To summarize global rates of NVP as reported in the literature using
      meta-analysis. METHODS: We searched Medline, Embase and Cochrane databases for
      all peer-reviewed articles reporting rates of NVP and/or hyperemesis gravidarum
      (HG). No restrictions were imposed on publication year or language. Numbers of
      women, studies and NVP rates were extracted and aggregated using a random effects
      model. Outcomes included: overall rates (i.e., women suffering any nausea or
      vomiting or both) in early and in late pregnancy, rates of nausea only, symptom
      severity, and HG rates. RESULTS: We identified 116 studies, rejecting 37 and
      accepting 79, of which 59 provided data for NVP (N=93,753 in 13 countries) and 26
      for HG (N= 6,155,578). All developed regions of the world were represented (2
      studies from Africa, 1 India; none from Latin America). Reported NVP rates varied
      from 35%-91% (median 69%); the meta-analytic average rate was 69.4% (CI95%:66.5%
      72.3%). Among pregnant women, 32.7% had nausea without vomiting and 23.5% overall
      had NVP continuing into the third trimester. NVP was rated as mild in 40%,
      moderate in 46% and severe in 14% of cases. The prevalence of HG was 1.1%
      (CI95%:0.8%-1.3%), with a range of 0.3%-3.6%. CONCLUSIONS: Almost 70% of women
      worldwide experience NVP, but reported rates vary widely. HG, the most severe
      form, affects 1.1%.

PMID- 23863574
TI  - Infection with hemotropic Mycoplasma species in patients with or without
      extensive arthropod or animal contact.
AB  - PCR amplification targeting the 16S rRNA gene was used to test individuals with
      and without extensive arthropod and animal contact for the possibility of
      hemotropic mycoplasma infection. The prevalence of hemotropic mycoplasma
      infection (4.7%) was significantly greater in previously reported cohorts of
      veterinarians, veterinary technicians, spouses of veterinary professionals, and
      others with extensive arthropod exposure and/or frequent animal contact than in a
      previously reported cohort of patients examined by a rheumatologist because of
      chronic joint pain or evidence of small-vessel disease (0.7%). Based upon DNA
      sequence analysis, a Mycoplasma ovis-like species was the most prevalent organism
      detected; however, infection with "Candidatus Mycoplasma haematoparvum" and a
      potentially novel, but incompletely characterized, hemotropic Mycoplasma species
      was also documented. Historical exposure to animals and arthropod vectors that
      can harbor hemotropic Mycoplasma spp. should be considered during epidemiological
      investigations and in the evaluation of individual patients. 

PMID- 23863576
TI  - [Current state of oncolytic virotherapy in Japan].
AB  - Oncolytic virotherapy is an emerging treatment strategy that uses replication
      competent viruses to destroy cancers. Recent advances include preclinical proof
      of feasibility for a single-shot virotherapy cure, identification of drugs that
      accelerate intratumoral virus propagation, and strategies to maximize the
      immunotherapeutic action of oncolytic viruses. The primary clinical milestone has
      been completion of accrual in a phase 3 trial of intratumoral herpes simplex
      virus therapy using OncoVEX for metastatic melanoma. In Japan, clinical
      treatments such as oncolytic adenoviruses(OBP-301)for esophageal cancer and
      oncolytic herpes simplex viruses(G47b)for brain cancer have accelerated
      considerably. We hope that a steady stream of new oncolytic viruses will enter
      the clinical arena in our country. 

PMID- 23863578
TI  - [The Tokyo Metropolitan Government plan to promote the cancer control program].
AB  - Within the framework of the National Cancer Act, the Tokyo Metropolitan
      Government has executed a plan to promote the cancer control programs since 2008.
      The effort has resulted in substantial outcomes in the last 5 years. Or reviewing
      the past plan and in compliance with the National Basic Plan to Promote Cancer
      Control Program, which was initiated in 2012, the new Tokyo Plan will be launched
      this fiscal year. This plan focuses on cancer prevention, early detection, the
      provision of high-level and comprehensive cancer medical services, the
      identification of anxiety in patients cancer and their families, and the
      advancement of cancer registration and research activities. 

PMID- 23863577
TI  - [The basic plan to promote cancer control in Japan].
AB  - Cancer has been the leading cause of death in Japan since 1981. The Japanese
      government implemented the Comprehensive 10-year Strategy for Cancer Control in
      1984, following which the Second- and Third-term Comprehensive 10-year Strategy
      for Cancer Control have been implemented every 10years to promote cancer research
      and disseminate high-quality cancer medical services. The Cancer Control Act was
      approved in June 2006, and the law has been implemented since April 2007. Based
      on this law, the Basic Plan to Promote Cancer Control program was discussed by
      the Cancer Control Promotion Council and approved by the Cabinet of Japan in June
      2007. This plan was launched in June 2007, and covered 5 fiscal years from 2007
      to 2011. It also provides a model for developing the Prefectural Plan to Promote
      Cancer Control. The Basic Plan needs to be updated at least every 5 years under
      the Cancer Control Act; therefore, the Phase Two Basic Plan was approved by the
      Japanese Cabinet in June 2012. Although the first plan was limited to medicine or
      medical care, the second plan was broadened to include social undertakings such
      as patient support in terms of job acquisition or student education for an
      indepth understanding of cancer. This paper includes the history of cancer
      control promotion in Japan and viewpoints on the basic plan for cancer control. 

PMID- 23863579
TI  - [Brief description of the revised plan to promote cancer control programs in
      Miyagi].
AB  - In Japan, chief pillars of cancer control are improvement of cancer prevention,
      early detection of cancer and promotion of cancer research for treatment of
      advanced cancer. To promote cancer control in Japan, the Cancer Control Act was
      established in April 2007 in which a variety of goals for cancer control were
      clearly defined. Based on the Act, the Basic Plan to Promote Cancer Control
      Programs made in June 2007 and, then, the Plan to Promote Cancer Control Programs
      in each of the administrative division of Japan including Tokyo, Hokkaido and 45
      prefectures were carried out all over Japan during 2007 to 2011. Since the first
      5-year term of the Basic Plan was finished, the Basic Plan was revised in June
      2012 and the revised Plans in Tokyo, Hokkaido and 45 prefectures have been
      published in 2013. Here, the first and revised Plan to Promote Cancer Control
      Programs in Miyagi was briefly described. 

PMID- 23863580
TI  - [Promotion plan for the promotion of cancer: coping measures at Matsuyama Red
      Cross Hospital in Ehime prefecture - the current state of affairs at the
      hospital's cancer treatment promotion office].
AB  - Recent cancer control strategies in Japan have been aimed at lowering morbidity
      and mortality rates, based on the Thirdterm Comprehensive 10-year Strategy for
      Cancer Control initiated by the Japanese government. In April 2007, the Cancer
      Control Basic Law was promulgated to necessitate promotion of cancer control by
      national and local authorities. In June 2007, the Japanese Health Ministry
      released a plan for the promotion of measures to cope with cancer. The cancer
      control measures adopted by the Matsuyama Red Cross Hospital(MRCH)in Ehime
      Prefecture were as follows: .Progress in the promotion of measures to cope with
      cancer in Ehime, including a review of 2012, problems with new treatment methods
      for childhood cancer, employment of cancer patients, and promotion of home care.
      .Cancer treatment measures adopted by MRCH as a hub medical institution for the
      past 5 years. .The distinctive efforts of the intensive professionals team at the
      Cancer Treatment Promotion Office for cancer treatment at MRCH, and its work on
      cancer care from the 4 perspectives of the balanced scorecard in accordance with
      the basic policy of MRCH. 

PMID- 23863581
TI  - [Second-line FOLFIRI plus bevacizumab for patients with metastatic colorectal
      cancer after resection of the primary lesion].
AB  - The efficacy and safety of bevacizumab(BV), combined with infusional 5
      fluorouracil/leucovorin(5-FU/LV)plus irinotecan(FOLFIRI)as the second-line
      treatment for metastatic colorectal cancer(mCRC)after resection of the primary
      lesion, have not been fully clarified. We examined clinical results of 35
      patients on BV plus FOLFIRI at our hospital, and investigated the efficacy of BV
      plus FOLFIRI in mCRC patients who failed oxaliplatin-containing regimens(26
      patients were treated with BV at a dose of 5mg/kg, 3 patients with BV 10mg/kg,
      and 6 patients had BV increased from 5mg/kg to 10mg/kg). The average frequency of
      BV plus FOLFIRI treatment was 13. 9 times, and the average length of treatment
      was 10. 0 months. The overall response rate was 17. 1%(CR 1 patient, PR 5
      patients, SD 21 patients, PD 8 patients). The median PFS was 11. 0 months for
      FOLFIRI plus BV after first-line chemotherapy, and the median OS was 23. 0
      months. The adverse events were 77. 1%(>Grade 3, 55. 5%)and the BV-associated
      adverse event was grade 3 hypertension(2 patients). The FOLFIRI plus BV regimen
      is an active and well-tolerated second-line chemotherapy treatment for patients
      with mCRC after resection of the primary lesion. 

PMID- 23863582
TI  - [Efficacy and safety of cetuximab+irinotecan for unresectable advanced or
      recurrent colorectal cancer].
AB  - BACKGROUND: In July 2008, cetuximab treatment for unresectable advanced or
      recurrent colorectal cancer was approved in Japan, but there have been few
      reports on this therapy in Japan. PURPOSE: We retrospectively analyzed the
      efficacy and safety of cetuximab(Cmab)+irinotecan(CPT-11)for unresectable
      advanced or recurrent colorectal cancer from October 2008 to April 2010 at 5
      centers in the Kanagawa region. PATIENTS AND METHODS: The number of patients
      enrolled was 38, all of whom were treated after second-line therapy. RESULTS: The
      RR was 24%. DCR was 68%. TTF was 105 days and OS was 242 days. CONCLUSION: At 5
      centers, Cmab+CPT-11 was an effective and safe treatment after second-line
      therapy.

PMID- 23863583
TI  - [Water for the preparation of upper gastrointestinal endoscopy after
      gastrectomy].
AB  - For patients who have undergone gastrectomy for gastric cancer, a follow-up by
      upper gastrointestinal endoscopy is required. However, it is sometimes very
      difficult to observe the remnant stomach due to a significant amount of residual
      food. We evaluated the reduction of food residue by drinking water as preparation
      before upper gastrointestinal endoscopy in postpartial gastrectomy patients. We
      compared two groups. In the water group, patients drank 500 mL water after dinner
      on the evening before endoscopy, and on the day of endoscopy they drank 350 mL
      water before the examination. In the control group, patients drank nothing after
      dinner, and nothing on the day of endoscopy. In the water group, food residue in
      the remnant stomach was reduced. In patients who underwent proximal gastrectomy
      or pylorus-preserving gastrectomy, food residue in the remnant stomach was not
      reduced by drinking water. However, in patients with distal gastrectomy, food
      residue was reduced by drinking water. Drinking water before upper
      gastrointestinal endoscopy is safe with no risk of complications, and our results
      suggested that drinking water effectively reduced food residue in the remnant
      stomach before endoscopic examination. 

PMID- 23863584
TI  - [Complications after implantation of subcutaneous central venous port].
AB  - We retrospectively reviewed 500 cases who were implanted with subcutaneous
      central venous port(CV port)in our institution from Jan. 2007 to Nov. 2011, to
      investigate the complications arising after CV port implantation. The purpose of
      CV port implantation was chemotherapy access in 279 cases and home parenteral
      nutrition in 221 cases. The primary diseases were malignancy in 441
      cases(colorectal cancer 252 cases, gastric cancer 54 cases, etc.)and benign
      diseases in 59 cases. Seven patients(1. 4%)had complications at
      implantation(pneumothorax 6 cases, catheter migration 1 case). Forty-three
      patients(8. 6%)had complications after port implantation. Among them, 18 suffered
      port infection, 10 had obstruction of the catheter system, 4 developed skin
      ulceration, 4 developed port rotation, 3 had venous thrombosis, and 3 developed
      catheter migration. The cumulative patency rates after 1, 2, and 3 years were 90.
      7%, 81. 2%, and 74. 6%, respectively. Complications after port implantation were
      more frequently developed in home parenteral nutrition than in chemotherapy. 

PMID- 23863585
TI  - [Comparison of antiemesis effects of granisetron, aprepitant and dexamethasone to
      palonosetron, aprepitant and dexamethasone in treatment of high-emetic risk
      chemotherapy-induced nausea and vomiting - a retrospective study for efficacy and
      safety in a single institute].
AB  - Nausea and vomiting are among the most problematic symptoms experienced by
      patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)
      receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are
      now the standard therapies for preventing chemotherapy-induced nausea and
      vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and
      anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist
      is a proper treatment for combined use with aprepitant and dexamethasone, we
      conducted a questionnaire survey, which used the numerical rating scale(NRS), for
      comparing palonosetron with granisetron in the same patient. Palonosetron showed
      a significant improvement of nausea for both acute(within 24 hours)and delayed
      phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or
      anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety
      profile. Our study suggests that palonosetron-based antiemetic treatment will be
      a preferred choice for preventing CINV following highly emetogenic chemotherapy. 

PMID- 23863586
TI  - [A case of triple-negative breast cancer achieved pCR by epirubicin and
      cyclophosphamide(EC)therapy followed by gemcitabine plus paclitaxel combination
      preoperative therapy].
AB  - A 59-year-old woman was diagnosed with triple-negative breast
      cancer(TNBC)(T2N0M0)and treated with primary systemic therapy. The patient was
      treated with 4 courses of epirubicin and cyclophosphamide(EC)therapy every 3
      weeks, followed by weekly gemcitabine-paclitaxel combination therapy. As she was
      judged to have achieved a partial response(PR) by ultrasound and CT examination
      after eight courses, she underwent partial resection of the left breast. CR was
      revealed by the pathological examination of the resected specimen. Gemcitabine
      paclitaxel combination therapy seems to be a one of the useful preoperative
      chemotherapies for TNBC. 

PMID- 23863587
TI  - [A patient with primary breast cancer who responded remarkably well to
      neoadjuvant chemotherapy with FEC100 followed by Abraxane].
AB  - A 49-year-old woman visited our hospital presentind with a right breast lump. She
      underwent core needle biopsy, and her disease was diagnosed as breast
      cancer(invasive ductal carcinoma, ER slightly positive, PgR and HER2 negative).
      We chose neoadjuvant chemotherapy because the tumor size was over 3 cm in
      diameter with a histological grade III, and she asked to have her breast
      conserved. Because she had an allergy to alcohol, we treated her with FEC100
      followed by Abraxane(260mg/ m2)q3W for 4 courses. After chemotherapy, she
      received breast conserving therapy. During the treatment with Abraxane, the
      patient was very well and showed no major side effects except for grade 3
      neutropenia was found on an outpatient basis. After chemotherapy, breast MRI
      detected no invasive lesion. Pathological examination showed pCR. We concluded
      that Abraxane was a good option as neoadjuvant chemotherapy for early breast
      cancer. 

PMID- 23863588
TI  - [A case of brain abscess secondary to bisphosphonate-related osteonecrosis of the
      jaws in metastatic bone lesions from breast carcinoma].
AB  - Bisphosphonates have been used clinically as highly effective drugs in the
      treatment of hypercalcemia of malignancy, and bone metastasis of solid cancers.
      Despite these benefits, however, the emergence of bisphosphonate-related
      osteonecrosis of the jaws has become a growing and significant problem in a
      subset of patients receiving these drugs. We report a rare case of brain abscess
      secondary to BRONJ in metastatic bone lesions from breast carcinoma. 

PMID- 23863589
TI  - [Complete response after sorafenib therapy plus zoledronic acid for advanced
      hepatocellular carcinoma with bone metastasis - a case report].
AB  - Sorafenib is an oral multi-kinase inhibitor that targets tumor growth and
      angiogenesis signal transduction pathways. Two global phase III trials showed
      that sorafenib prolonged the survival of patients with advanced hepatocellular
      carcinoma (HCC). Based on the positive results of these trials, Japan approved
      sorafenib for advanced HCC in May 2009. However, in the SHARP trial and the Asia
      Pacific trials, no cases of complete response(CR)were reported. Thereafter, only
      a relatively small number of CR cases were reported for sorafenib therapy. We
      herein report the case of a 64-year-old Japanese man infected with hepatitis B
      virus who developed bone metastasis 9 months after resection of HCC. Sorafenib
      therapy plus zoledronic acid was initiated. The patient achieved a CR after 15
      months of therapy, and there has been no sign of recurrence 12 months following
      cessation of administration. Regarding toxicity, the patient developed a grade 2
      hand foot skin reaction that required a temporary 50% dose reduction of
      sorafenib. To our knowledge, this is the first case of CR in advanced HCC with
      bone metastasis treated with sorafenib plus zoledronic acid. 

PMID- 23863590
TI  - [Clinical benefit of full-dose gemcitabine for advanced pancreatic cancer
      refractory to S-1+gemcitabine].
AB  - A 62-year-old man with pancreatic body cancer underwent distal pancreatectomy
      without adjuvant gemcitabine(GEM). Because the pancreatic cancer recurred 4
      months after surgery, however, he was treated with combination chemotherapy(S-
      1+GEM at 750mg/m2). Unfortunately, this combination regimen was ineffective;
      therefore S-1 was withdrawn and full-dose GEM was administered as second-line
      treatment. One year of full-dose GEM showed a significant clinical benefit,
      completely eliminating multiple pulmonary metastases even after a 3-month
      suspension of chemotherapy. Our findings suggest that GEM monotherapy is a useful
      mainstream treatment for advanced pancreatic cancer. 

PMID- 23863591
TI  - [Pathological complete response in a case of advanced esophageal cancer invading
      aorta treated by preoperative chemotherapy with docetaxel and cisplatin plus 5
      FU].
AB  - The patient was a 64-year-old man, diagnosed as cStage IVa esophageal cancer
      invading the aorta with lymph node metastasis. He received combination
      chemotherapy with docetaxel/cisplatin/5-FU(DFP therapy). After one course, CT and
      endoscopic examination showed remarkable reduction of the primary lesion and
      lymph node metastasis. We performed subtotal esophagectomy and gastric tube
      reconstruction by the retroposterior mediastinum route. The pathological specimen
      evidenced fibrosis and infiltration of inflammatory cells on almost all layers,
      but showed no viable malignant cells in the middle thoracic esophagus. Therefore,
      the pathological effect was judged as Grade 3(pCR). This case suggested that DFP
      combination chemotherapy may prove to be a useful treatment for advanced
      esophageal cancer with invasion to other organs. 

PMID- 23863592
TI  - [Bevacizumab therapy for a colorectal cancer patient or hemodialysis with hepatic
      metastasis].
AB  - We report our experience with a case of colorectal cancer treated with
      chemotherapy for a liver metastasis patient on hemodialysis. The patient was a 67
      year-old man with a history of chronic renal failure, who was on hemodialysis
      since 2005. High anterior resection was performed for sigmoid colon and rectal
      cancer in January, 2010. After starting chemotherapy while planning to use
      FOLFOX6+bevacizumab(BV)as a postoperative standard chemotherapy, in combination
      with hemodialysis three times a week while performing dose escalation,
      administration postponement was continued for myelosuppression that was
      considered to be the effect of oxaliplatin. Oxaliplatin was administered for only
      2 courses, and was then changed to BV+sLV5FU2 therapy. We continued treating the
      metastases approximately on schedule. Imaging revealed, the liver metastases were
      CR because they had disappeared. The BV use case of the dialysis case had few
      reports, but was thought to be able to use it by careful administration safely. 

PMID- 23863593
TI  - [A case of advanced gastric cancer diagnosed as stage IV responding to combined
      modality therapy and surviving for a long duration].
AB  - A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly
      differentiated adenocarcionoma), with multiple para-aortic lymph node and liver
      metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with
      docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we
      confirmed that the para-aortic lymph nodes and liver metastasis became small.
      Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node
      dissection. Additionally, we performed an intraoperative radiofrequency ablation
      to the scar of the liver metastasis. Histopathologically, we identified lymph
      node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant
      chemotherapy. At seven years since the operation, the patient has shown no signs
      of recurrence. Combined modality therapy for advanced gastric cancer diagnosed
      with stage IV can be an effective treatment, so we hope that it will be
      established as a standard therapy. 

PMID- 23863594
TI  - [Approximately four years of survival benefits for a case of gastric cancer
      postoperative carcinomatous peritonitis by combined modality therapy].
AB  - Carcinomatous peritonitis may develop after operation for gastric cancer. As
      ascites are difficult to control, especially for gastric cancer postoperative
      carcinomatous peritonitis, many cases are difficult to treat. The present case
      was a female patient with carcinomatous peritonitis that occurred 2 years post
      surgery. Administration of docetaxel (DOC)and S-1 combination therapy achieved a
      complete response. However, she had a relapse of carcinomatous peritonitis 3
      years post-surgery. She underwent bypass operation, followed by DOC and S-1
      combination therapy again. She achieved a good quality of life for more than two
      years. As side effects in patients worsen with the repeated exposure to
      chemotherapy, continuing the same treatment is difficult. Therefore, we changed
      the therapy method to irinotecan(CPT-11)/cisplatin(CDDP)therapy, weekly
      paclitaxel(PTX)and methotrexate(MTX)/5-fluorouracil(5-FU)therapy, and bypass
      operation when necessary. Rapid progression of her condition was sequentially
      suppressed, allowing her to continue her everyday life. Overall, this treatment
      method provided survival benefits of approximately four years following the
      recurrence of carcinomatous peritonitis. 

PMID- 23863595
TI  - [A case of recurrent colon cancer developed thrombosis in superior mesenteric
      vein after chemotherapy].
AB  - A 48-year-old man was administered bevacizumab+FOLFOX for lymph node recurrence
      of colon cancer in the abdominal cavity, and developed serious thrombosis of the
      portal system after 6 courses of the chemotherapy. We discontinued it promptly
      and anticoagulant therapy with urokinase was started immediately, but a complete
      dissolution was not achieved. Preservation therapy using anticoagulants for a
      long duration was effective for controling the of clinical symptom of thrombosis.
      The result of 6 courses of chemotherapy was CR, and the effect continues today,
      without further treatment 2 years later. 

PMID- 23863596
TI  - [A case of necrotizing fasciitis developed in a patient with recurrent rectal
      cancer treated with chemotherapy].
AB  - A fifty-two-year-old female with advanced rectal cancer underwent low anterior
      resection and hysterectomy. After local pelvic recurrence, she underwent
      radiation therapy(50 Gy in total), and then chemotherapy(XELOX+bevacizumab)was
      started. However, left femoral pain developed after the second course of
      chemotherapy, and necrotizing fasciitis associated with lower bowel perforation
      was found. Although bowel perforation is known as a serious side-effect of
      bevacizumab, its association with fasciitis is rare. 

PMID- 23863597
TI  - [A case of synchronous liver metastasis originating from advanced gastric cancer
      treated with combination chemotherapy involving S-1 and surgical intervention].
AB  - A 71-year-old man was diagnosed with gastric cancer[cT4, cN0, cH1(S6), cP0, cM0,
      cStage IV]and underwent distal gastrectomy with cholecystectomy, partial
      colectomy for the invasion to the mesentery of transverse colon, and partial
      hepatectomy for metastatic liver tumor(segment 6). Although chemotherapy with S
      1+CDDP was administered after the operation, a recurrent lesion appeared in the
      remnant of liver(segment 6). The chemotherapy regimen was changed to S-1+CPT-11.
      Since the only recurrent tumor was found in the remnant liver, it was resected.
      After S-1 chemotherapy, no recurrence has been detected since the first
      operation. A good outcome was obtained for this patient with synchronous liver
      metastasis and the recurrence remnant liver originating from gastric cancer,
      possibly as a result of the combination of chemotherapy and surgical resection
      for the primary lesion and liver metastasis. 

PMID- 23863598
TI  - [A case of hyperammonemic encephalopathy related to 5-FU in an aged patient with
      recurrent colon cancer treated with FOLFIRI therapy].
AB  - We report a case of hyperammonemic encephalopathy related to 5-FU in an aged
      patient with recurrent colon cancer treated with FOLFIRI therapy. An 80-year-old
      man underwent right hemicolectomy for cecal cancer. After 10 months, surgical
      resection was performed for its local recurrence. He was then treated with
      FOLFIRI therapy, and during the fifth course, he presented with a sudden onset of
      congestive disturbances. Through radiographic examination and laboratory data,
      only hyperammonemia was found; he was therefore diagnosed with hyperammonemic
      encephalopathy. By starting branchedamino acid solutions for its treatment, his
      consciousness and serum ammonia were promptly improved. Hyperammonemic
      encephalopathy related 5-FU is caused by increasing ammonia production and its
      metabolic inhibition, and is worsened by renal dysfunction, dehydration,
      constipation, infections, or body weight loss. On account of the potential
      decrease of metabolic function of liver and kidney, an aged person tends to have
      hyperammonnemia more than a youth. Clinicians should be aware of the adverse
      events associated with hyperammonemia when then administer a large amount of 5-FU
      to elderly patients. 

PMID- 23863599
TI  - Gonioscopic findings associated with a positive dark-room provocative test in
      narrow angles after laser iridotomy.
AB  - PURPOSE: To determine clinical factors and ultrasound biomicroscopic (UBM)
      findings associated with a positive prone dark-room provocative test (DRPT) in
      patients with narrow angles after laser peripheral iridotomy (LPI). PATIENTS AND
      METHODS: Seventeen eyes with a positive DRPT and 18 eyes with a negative DRPT
      were included in this comparative case series, based on chart review of patients
      diagnosed with narrow angles persisting after LPI who had undergone clinical
      evaluation with a 45-minute DRPT and UBM imaging. Subjects with a positive DRPT
      [an increase of intraocular pressure (IOP) of 6 mm Hg or more] were compared with
      a negative DRPT control group. Charts were reviewed for age, refraction and
      gonioscopic examination. UBM measurements obtained included the anterior chamber
      depth, angle opening distance at 500 MUm, angle recess area, anterior chamber
      angle, trabecular-ciliary process distance, iris thickness, iris-ciliary process
      distance, height of plateau, and distance of iris-cornea contact. RESULTS: Mean
      increase in IOP was 11.1+/-3.5 mm Hg in the positive DRPT group (group A) and
      0.9+/-0.1 mm Hg in the negative DRPT (group B). On indentation gonioscopy,
      patients in group A had significantly more synechial angle closure of 180 degrees
      or more (35% vs. 0%, P=0.008), more frequent double-hump sign (59% vs. 11%,
      P=0.005), and significantly more patients in this group had at least one of these
      findings, (13/16 vs. 2/15, P=<0.001). Mean age did not differ between groups
      (P=0.88). There were significantly more women in group B (58% men in group A and
      83% women in group B, P=0.01). Mean refraction was +3.41+/-2.27 D in group A and
      +2.60+/-2.06 D in group B (P=0.32). There were no statistically significant
      differences in any of the UBM parameters between the 2 groups. CONCLUSIONS: A
      positive DRPT was found in patients presenting a more compromised drainage angle
      after LPI, due to anterior synechiae and/or an anteriorly positioned ciliary body
      as shown by the presence of a double-hump sign. DRPT may help identify patients
      at higher risk of intermittent increases in IOP among those presenting persistent
      narrow angles after LPI, and indentation gonioscopy remains an important step in
      evaluating these patients.

PMID- 23863600
TI  - Molecular mimicry: good artists copy, great artists steal.

PMID- 23863601
TI  - Endothelial activation and dysfunction in the pathogenesis of influenza A virus
      infection.
AB  - The development of severe influenza has been attributed, in part, to a heightened
      innate immune response. Recent evidence suggests that endothelial activation,
      loss of barrier function, and consequent microvascular leak may also serve
      important mechanistic roles in the pathogenesis of severe influenza. The aim of
      this review is to summarize the current evidence in support of endothelial
      activation and dysfunction as a central feature preceding the development of
      severe influenza. We also discuss the effect of influenza on platelet-endothelial
      interactions. 

PMID- 23863602
TI  - Community-acquired pneumonia infections by Acinetobacter baumannii: how does
      alcohol impact the antimicrobial functions of macrophages?

PMID- 23863603
TI  - Emerging therapeutic strategies to prevent infection-related microvascular
      endothelial activation and dysfunction.
AB  - Recent evidence suggests that loss of endothelial barrier function and resulting
      microvascular leak play important mechanistic roles in the pathogenesis of
      infection-related end-organ dysfunction and failure. Several distinct therapeutic
      strategies, designed to prevent or limit infection-related microvascular
      endothelial activation and permeability, thereby mitigating end-organ
      injury/dysfunction, have recently been investigated in pre-clinical models. In
      this review, these potential therapeutic strategies, namely, VEGFR2/Src
      antagonists, sphingosine-1-phosphate agonists, fibrinopeptide Bbeta 15-42,
      slit2N, secinH3, angiopoietin-1/tie-2 agonists, angiopoietin-2 antagonists,
      statins, atrial natriuretic peptide, and mesenchymal stromal (stem) cells, are
      discussed in terms of their translational potential for the management of
      clinical infectious diseases. 

PMID- 23863604
TI  - Common and pathogen-specific virulence factors are different in function and
      structure.
AB  - In the process of host-pathogen interactions, bacterial pathogens always employ
      some special genes, e.g., virulence factors (VFs) to interact with host and cause
      damage or diseases to host. A number of VFs have been identified in bacterial
      pathogens that confer upon bacterial pathogens the ability to cause various types
      of damage or diseases. However, it has been clarified that some of the identified
      VFs are also encoded in the genomes of nonpathogenic bacteria, and this finding
      gives rise to considerable controversy about the definition of virulence factor.
      Here 1988 virulence factors of 51 sequenced pathogenic bacterial genomes from the
      virulence factor database (VFDB) were collected, and an orthologous comparison to
      a non-pathogenic bacteria protein database was conducted using the reciprocal
      best-BLAST-hits approach. Six hundred and twenty pathogen-specific VFs and 1368
      common VFs (present in both pathogens and nonpathogens) were identified, which
      account for 31.19% and 68.81% of the total VFs, respectively. The distribution of
      pathogen-specific VFs and common VFs in pathogenicity islands (PAIs) was
      systematically investigated, and pathogen-specific VFs were more likely to be
      located in PAIs than common VFs. The function of the two classes of VFs were also
      analyzed and compared in depth. Our results indicated that most but not all T3SS
      proteins are pathogen-specific. T3SS effector proteins tended to be distributed
      in pathogen-specific VFs, whereas T3SS translocation proteins, apparatus
      proteins, and chaperones were inclined to be distributed in common VFs. We also
      observed that exotoxins were located in both pathogen-specific and common VFs. In
      addition, the architecture of the two classes of VFs was compared, and the
      results indicated that common VFs had a higher domain number and lower domain
      coverage value, revealed that common VFs tend to be more complex and less compact
      proteins.

PMID- 23863605
TI  - Constant domains influence binding of mouse-human chimeric antibodies to the
      capsular polypeptide of Bacillus anthracis.
AB  - Our laboratory previously described the binding characteristics of the murine
      IgG3 monoclonal antibody (MuAb) F26G3. This antibody binds the poly-glutamic acid
      capsule (PGA) of Bacillus anthracis, an essential virulence factor in the
      progression of anthrax. F26G3 IgG3 MuAb binds PGA with a relatively high
      functional affinity (10 nM), produces a distinct "rim" quellung reaction, and is
      protective in a murine model of pulmonary anthrax. This study engineered an IgG
      subclass family of F26G3 mouse-human chimeric antibodies (ChAb). The F26G3 ChAbs
      displayed 9- to 20-fold decreases in functional affinity, as compared with the
      parent IgG3 MuAb. Additionally, the quellung reactions that were produced by the
      ChAbs all differed from the parent IgG3 MuAb in that they appeared "puffy" in
      nature. This study demonstrates that human constant domains may influence
      multiple facets of antibody binding to microbial capsular antigens despite their
      spatial separation from the traditional antigen-binding site. 

PMID- 23863607
TI  - Alcohol impairs J774.16 macrophage-like cell antimicrobial functions in
      Acinetobacter baumannii infection.
AB  - Acinetobacter baumannii (Ab) is a common cause of community-acquired pneumonia
      (CAP) in chronic alcoholics in tropical and sub-tropical climates and associated
      with a > 50% mortality rate. We demonstrated that exposure of J774.16 macrophage
      like cells to physiological alcohol (EtOH) concentrations decreased phagocytosis
      and killing of Ab. EtOH-mediated macrophage phagocytosis dysfunction may be
      associated with reduced expression of GTPase-RhoA, a key regulator of the actin
      polymerization signaling cascade. EtOH inhibited nitric oxide (NO) generation via
      inducible NO-synthase inactivation, which enhanced Ab survival within
      macrophages. Additionally, EtOH alters cytokine production resulting in a
      dysregulated immune response. This study is a proof of principle which
      establishes that EtOH might exacerbate Ab infection and be an important factor
      enhancing CAP in individuals at risk. 

PMID- 23863606
TI  - Genetic changes that accompanied shifts of low pathogenic avian influenza viruses
      toward higher pathogenicity in poultry.
AB  - Avian influenza viruses (AIV) of H5 and H7 subtypes exhibit two different
      pathotypes in poultry: infection with low pathogenic (LP) strains results in
      minimal, if any, health disturbances, whereas highly pathogenic (HP) strains
      cause severe morbidity and mortality. LPAIV of H5 and H7 subtypes can
      spontaneously mutate into HPAIV. Ten outbreaks caused by HPAIV are known to have
      been preceded by circulation of a predecessor LPAIV in poultry. Three of them
      were caused by H5N2 subtype and seven involved H7 subtype in combination with N1,
      N3, or N7. Here, we review those outbreaks and summarize the genetic changes
      which resulted in the transformation of LPAIV to HPAIV under natural conditions.
      Mutations that were found directly in those outbreaks are more likely to be
      linked to virulence, pathogenesis, and early adaptation of AIV.

PMID- 23863608
TI  - Paradoxical effect to caspofungin in Candida species does not confer survival
      advantage in a Drosophila model of candidiasis.

PMID- 23863609
TI  - Mycobacterium tuberculosis... Can we beat it? Report from a Euroscicon conference
      2013.

PMID- 23863612
TI  - The management of nausea and vomiting of pregnancy and hyperemesis gravidarum--a
      2013 update.
AB  - Nausea and vomiting of pregnancy (NVP) affects up to 85% of all pregnancies, yet
      many physicians are uncertain as to how to best treat their patients in the
      presence of controversial data on fetal risks. This review provides an update on
      the management of NVP, including pharmacological and non pharmacological
      approaches Due to a high rate of recurrent symptoms, it is important for women to
      receive early treatment to reduce the severity of symptoms with the aim of
      preventing hospitalization and improving quality of life. 

PMID- 23863610
TI  - Estrogen reduces mechanical injury-related cell death and proteoglycan
      degradation in mature articular cartilage independent of the presence of the
      superficial zone tissue.
AB  - OBJECTIVE: To study the effect of 17beta-estradiol (E2) and the superficial zone
      (SFZ) on cell death and proteoglycan degradation in articular cartilage after a
      single injurious compression in vitro. METHOD: Cartilage explants from the
      femoropatellar groove of 2 year old cows with or without the SFZ were cultured
      serum-free with physiological concentrations of E2 and injured by an unconfined
      single load compression (strain 50%, velocity 2 mm/s). After 96 h cell death was
      measured histomorphometrically (nuclear blebbing (NB) and TUNEL staining) and
      release of glycosaminoglycans (GAG) by DMMB assay. RESULTS: Injurious compression
      increased significantly the number of cells with NB and TUNEL staining and
      release of GAG. Physiological concentrations of E2 prevented the injury-related
      cell death and reduced the GAG release significantly in a receptor-mediated
      manner (shown by co-stimulation with the antiestrogen fulvestrant/faslodex/ICI
      182,780). The presence of the SFZ did not alter the NB response to either the
      mechanical injury or E2, but reduced the overall release of GAG significantly.
      CONCLUSION: E2 prevents injury-related cell death and GAG release, and might be
      useful for the development of treatment options for either cartilage-related
      sports injuries or osteoarthritis (OA). The SFZ does not seem to play an
      important role in (1) the E2-related tissue response and (2) the mechanically
      induced cell death in deeper regions of the explants and GAG release. The latter
      might be related to the unconfined nature of the injury model.

PMID- 23863613
TI  - An intuitive approach to understanding the attributable fraction of disease due
      to a risk factor: the case of smoking.
AB  - The health damage from tobacco use has been studied intensively, yet quantifying
      the precise burden of disease and death due to smoking is a complex problem, and
      consequently open to manipulation by interested parties. The goals of this paper
      are to clearly communicate the concept of the attributable fraction (AF), i.e.,
      the proportion of disease in a population which can be attributed to a risk
      factor, and to understand the relationship between the AF, the prevalence of
      exposure in a population, and the relative risk of disease given the exposure.
      The current approach to calculating the AF is summarized. An intuitive formula is
      proposed, with accompanying graphical illumination. For diseases caused by
      smoking, the AF of disease due to smoking increases with the prevalence of
      smoking and with the relative risk of disease due to smoking. The proposed method
      has the potential to help health professionals and decision makers understand the
      concept of the burden of disease due to smoking or other lifestyle,
      environmental, and occupational factors, in the context of public health
      importance. This will aid sound decision-making in public health policy. 

PMID- 23863615
TI  - Bevacizumab in advanced breast cancer: a new model for the assessment of activity
      in non-first-line treatment regimens.
AB  - The activity of bevacizumab (BVZ) in advanced lines is not well known. In the
      treatment of metastatic breast cancer, the response rate and time to treatment
      failure (TTF) decrease with progression through successive therapeutic lines. The
      objective of this study was to compare BVZ activity in advanced treatment lines
      with that achieved in the previous line in routine clinical practice. Ninety-six
      patients who had received BVZ treatment in second or subsequent treatment lines
      were selected from five Spanish hospitals. Analysis was carried out of the
      differences in TTF and response rate in the lines with BVZ and those in earlier
      lines. Data analysis was carried out in two different ways: (a) by comparing
      treatment groups according to the treatment line received, using a Cox regression
      model with random effects, and the McNemar test to analysis the response rate,
      and (b) by comparing intrapatient data, using the Wilcoxon signed-rank test. In
      62 patients, the TTF (adjusted for treatment line) was longer in the BVZ
      treatment line than that in the previous line. In the BVZ lines, there was a
      significant reduction in the probability of treatment failure [hazard ratio 0.52;
      95% confidence interval (CI) 0.38-0.71]. The median TTF was 4.27 months (95% CI
      3.7-5) in the previous line and 6.18 months (95% CI 5.5-7.93) in the BVZ line.
      The percentage of patients with an objective response was 33.3% in the previous
      lines and 52.1% (P=0.005) in the BVZ line. Contrary to expectation, more patients
      showed better results with the BVZ line than with the previous line. BVZ
      treatment in advanced lines improves the results obtained in previous treatment
      lines. This suggests that BVZ is active in advanced lines and that it produces
      favourable changes in the natural history of patients with metastatic breast
      carcinoma.

PMID- 23863614
TI  - Distal and proximal factors of health behaviors and their associations with
      health in children and adolescents.
AB  - OBJECTIVE: The aim of the present paper was to analyze factors affecting distal
      and proximal health behavior within a biopsychosocial model for examining their
      interactions and associations with respect to health. METHODS: Path analysis was
      based on the nationwide, cross-sectional German Health Interview and Examination
      Survey for Children and Adolescents (2003 to 2006). The data was collected from
      4,529 participants with an average age of 9.45 years (SD = 4.01). Socio
      demographic data, psychosocial factors and health behavior were assessed via
      questionnaire. Participants also underwent physical fitness tests and a medical
      examination. RESULTS: Over the five levels of the model analyzed with
      socioeconomic status, immigration background, and rural-urban differences on the
      first level; physical activity of relatives and peers, intrinsic motivation, and
      quality of life on the second level; eating patterns, sedentary behavior, and
      physical activity on the third level; physical fitness and objective health on
      the fourth level; and health complaints and subjective health on the fifth level;
      direct, moderation, and mediation effects could be shown. CONCLUSIONS: Several
      distal and proximal factors are needed to take account of the multivariate
      complexity of health: e.g., immigration background affected health behaviors only
      indirectly and the effect of physical activity on objective health was mediated
      by physical fitness.

PMID- 23863616
TI  - Clinical relevance and utility of cetuximab-related changes in magnesium and
      calcium serum levels.
AB  - Hypomagnesemia and hypocalcemia are common adverse events during cetuximab
      treatment. The influence of the chemotherapeutic combination on serum levels is
      unknown and the predictive value is currently under discussion. This analysis
      investigated 79 patients who had received cetuximab for at least 6 weeks in the
      day clinic of the Comprehensive Cancer Center, University of Munich. Calcium and
      magnesium serum levels were analyzed weekly; tumor response and adverse events
      were followed. Thirty-eight patients had metastatic colorectal cancer (mCRC) and
      the predictive value of hypomagnesemia was tested in these patients. During
      therapy, calcium serum levels decreased to about 97% of the baseline levels and
      were maintained for the duration of treatment. Magnesium levels showed a
      significant time-dependent decrease. Serum levels of magnesium were lower when
      cetuximab was combined with a platinum derivative. After a treatment duration of
      12 weeks, magnesium levels decreased to 70% in platinum-treated patients, whereas
      they decreased to only 90% of baseline in patients who did not receive platinum
      therapy. In patients treated for mCRC, a decrease of serum magnesium below 95% of
      the baseline levels 14 days after initiating treatment separated patients
      significantly in terms of survival times. Magnesium levels decrease in a time
      dependent manner during cetuximab therapy. As hypomagnesemia was more prominent
      in patients receiving platinum agents, magnesium measurements may be advised in
      these patients. In mCRC patients treated with cetuximab, day-14 magnesium serum
      levels correlated with treatment efficacy.

PMID- 23863617
TI  - Setups for in vitro assessment of RFID interference on pacemakers.
AB  - The aim of this study is to propose setups for in vitro assessment of RFID
      (radiofrequency identification) interference on pacemakers (PM). The voltage
      induced at the input stage of the PM by low-frequency (LF) and high-frequency
      (HF) RFID transmitters has been used to quantify the amount of the interference.
      A commercial PM was modified in order to measure the voltage at its input stage
      when exposed to a sinusoidal signal at 125 kHz and 13.56 MHz. At both
      frequencies, two antennas with different dimensions (diameter = 10 cm and 30 cm,
      respectively) were used to generate the interfering field, and the induced
      voltage was measured between the lead tip and the PM case (unipolar voltage), and
      between the tip and ring electrodes (bipolar voltage). The typical lead
      configurations adopted in similar studies or proposed by international standards,
      as well as lead paths closer to actual physiological implants were tested. At 125
      kHz, the worst-case condition differs for the two antennas: the 10 cm antenna
      induced the highest voltage in the two-loop spiral configuration, whereas the 30
      cm antenna in the 225 cm(2) loop configuration. At 13.56 MHz, the highest voltage
      was observed for both the antennas in the 225 cm(2) loop configuration. Bipolar
      voltages were found to be lower than the unipolar voltages induced in the same
      configurations, this difference being not as high as one could expect from
      theoretical considerations. The worst-case scenario, in terms of the induced
      voltage at the PM input stage, has been identified both for LF and HF readers,
      and for two sizes of transmitting antennas. These findings may provide the basis
      for the definition of a standard implant configuration and a lead path to test
      the EMI effects of LF and HF RFID transmitters on active implantable devices. 

PMID- 23863619
TI  - Contusion injury with chronic in vivo polyphenol supplementation: leukocyte
      responses.
AB  - INTRODUCTION: In vivo, daily proanthocyanidolic oligomer (PCO) supplementation
      before and after experimental skeletal muscle contusion injury has been shown to
      result in a blunted neutrophil response in tissue, quicker macrophage
      infiltration into muscle, and faster recovery due to a left shift in time course
      of inflammation. The current study investigated effects of PCO on circulatory
      neutrophils and macrophage subpopulations as well as in vitro neutrophil
      migration. METHODS: Primary cultured neutrophils obtained from control animals
      were incubated in media with 20% conditioned plasma. To obtain conditioned media,
      male Wistar rats were supplemented with PCO (20 mg.kg(-1)d(-1)) or placebo (PLA)
      for 2 wk before a mass-drop contusion injury. Conditioned plasma was prepared
      from blood collected at different time points after injury (12 h, 1 d, 3 d, and 5
      d). Macrophage subpopulation distribution, inflammatory cytokine, and
      myeloperoxidase levels were assessed for all time points. RESULTS: On day 1
      postinjury, circulating neutrophil numbers were significantly lower in PLA than
      PCO, suggesting that extravasation from the blood was reduced by PCO.
      Concurrently, neutrophil migration in vitro was blunted in the presence of
      conditioned plasma from PCO supplemented rats compared with PLA supplemented
      rats. Plasma M1 and M2c macrophage numbers differed over time and between groups.
      M1 macrophage numbers peaked on day 3 with PCO supplementation, followed by a
      rise in M2c macrophages on day 5, when M1 macrophages numbers were still high in
      PLA. CONCLUSIONS: We conclude that PCO supplementation limits neutrophil
      migration capacity in vitro despite a chemotactic gradient. Furthermore, the
      earlier appearance of type M2 macrophages suggests a switch to an anti
      inflammatory phenotype after injury even in circulation.

PMID- 23863618
TI  - Sedentary screen time and left ventricular structure and function: the CARDIA
      study.
AB  - INTRODUCTION: Sedentary screen time (watching TV or using a computer) predicts
      cardiovascular outcomes independently from moderate and vigorous physical
      activity and could affect left ventricular structure and function through the
      adverse consequences of sedentary behavior. PURPOSE: This study aimed to
      determine whether sedentary screen time is associated with measures of left
      ventricular structure and function. METHODS: The Coronary Artery Risk Development
      in Young Adults Study measured screen time by questionnaire and left ventricular
      structure and function by echocardiography in 2854 black and white participants,
      age 43-55 yr, in 2010-2011. Generalized linear models evaluated cross-sectional
      trends for echocardiography measures across higher categories of screen time and
      adjusting for demographics, smoking, alcohol, and physical activity. Further
      models adjusted for potential intermediate factors (blood pressure,
      antihypertensive medication use, diabetes, and body mass index). RESULTS: The
      relationship between screen time and left ventricular mass (LVM) differed in
      blacks versus whites. Among whites, higher screen time was associated with larger
      LVM (P < 0.001), after adjustment for height, demographics, and lifestyle
      variables. Associations between screen time and LVM persisted when adjusting for
      blood pressure, antihypertensive medication use, and diabetes (P = 0.008) but not
      with additional adjustment for body mass index (P = 0.503). Similar relationships
      were observed for screen time with LVM indexed to height, relative wall
      thickness, and mass-to-volume ratio. Screen time was not associated with left
      ventricular structure among blacks or left ventricular function in either race
      group. CONCLUSIONS: Sedentary screen time is associated with greater LVM in white
      adults, and this relationship was largely explained by higher overall adiposity.
      The lack of association in blacks supports a potential qualitative difference in
      the cardiovascular consequences of sedentary screen-based behavior.

PMID- 23863620
TI  - Reduced risk of incident kidney cancer from walking and running.
AB  - PURPOSE: This study aimed to test whether incident kidney cancer risk is
      associated with exercise energy expenditure (i.e., metabolic equivalents, 1 MET)
      when calculated from distance walked or run. METHODS: Hazard ratios (HR) and 95%
      confidence intervals (95% CI) from Cox proportional hazard analyses of self
      reported physician-diagnosed incident kidney cancer versus MET-hours per week in
      91,820 subjects recruited between 1991 and 1993 (7.7 yr follow-up of 42,833
      subjects) and between 1998 and 1999 (6.4 yr follow-up of 33,053 subjects) as part
      of the National Runners' Health Study and between 1998 and 1999 as part of the
      National Walkers' Health Study (5.7 yr follow-up of 15,934 subjects). RESULTS:
      Fifty-two incident cancers were reported. Age- and sex-adjusted risk declined
      1.9% per MET-hour per week run or walked (HR = 0.981, 95% CI = 0.964-0.997, P =
      0.02). Compared with walking or running below guidelines levels (<7.5 MET.h.wk(
      1)), the risk for incident kidney cancer was 61% lower for meeting the guidelines
      (HR = 0.39, 95% CI = 0.11-1.08, P = 0.07 for 7.5-12.5 MET.h.wk(-1)), 67% lower
      for exercising one to two times the recommended level (HR = 0.33; 95% CI = 0.15
      0.72, P = 0.005 for 12.6-25.1 MET.h.wk(-1)), and 76.3% lower for exercising two
      times or more the recommended level (HR = 0.24, 95% CI = 0.11-0.52, P = 0.0005
      for >= 25.2 MET.h.wk(-1)). Incident kidney cancer risk also increased in
      association with baseline body mass index (P = 0.002), smoking (P = 0.02), and
      hypertensive (P = 0.007) and diabetes medication use (P = 0.01); however,
      exercise-associated reductions in kidney cancer risk persisted for 12.6-25.1
      MET.h.wk(-1) (HR = 0.35, P = 0.01) and >= 25.2 MET.h.wk(-1) (HR = 0.29, P =
      0.004) vis-a-vis <7.5 MET.h.wk(-1) when also adjusted for body mass index,
      hypertension, diabetes, and pack-years smoked. CONCLUSION: Running and walking
      may reduce incident kidney cancer risk independent of its other known risk
      factors.

PMID- 23863621
TI  - Developmental differences in IFN signaling affect GATA1s-induced megakaryocyte
      hyperproliferation.
AB  - About 10% of Down syndrome (DS) infants are born with a transient
      myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first
      few months of life. About 20%-30% of these infants subsequently develop acute
      megakaryoblastic leukemia (DS-AMKL). Somatic mutations leading to the exclusive
      production of a short GATA1 isoform (GATA1s) occur in all cases of DS-TMD and DS
      AMKL. Mice engineered to exclusively produce GATA1s have marked megakaryocytic
      progenitor (MkP) hyperproliferation during early fetal liver (FL) hematopoiesis,
      but not during postnatal BM hematopoiesis, mirroring the spontaneous resolution
      of DS-TMD. The mechanisms that underlie these developmental stage-specific
      effects are incompletely understood. Here, we report a striking upregulation of
      type I IFN-responsive gene expression in prospectively isolated mouse BM- versus
      FL-derived MkPs. Exogenous IFN-alpha markedly reduced the hyperproliferation FL
      derived MkPs of GATA1s mice in vitro. Conversely, deletion of the alpha/beta IFN
      receptor 1 (Ifnar1) gene or injection of neutralizing IFN-alpha/beta antibodies
      increased the proliferation of BM-derived MkPs of GATA1s mice beyond the initial
      postnatal period. We also found that these differences existed in human FL versus
      BM megakaryocytes and that primary DS-TMD cells expressed type I IFN-responsive
      genes. We propose that increased type I IFN signaling contributes to the
      developmental stage-specific effects of GATA1s and possibly the spontaneous
      resolution of DS-TMD.

PMID- 23863622
TI  - Cross-species malaria immunity induced by chemically attenuated parasites.
AB  - Vaccine development for the blood stages of malaria has focused on the induction
      of antibodies to parasite surface antigens, most of which are highly polymorphic.
      An alternate strategy has evolved from observations that low-density infections
      can induce antibody-independent immunity to different strains. To test this
      strategy, we treated parasitized red blood cells from the rodent parasite
      Plasmodium chabaudi with seco-cyclopropyl pyrrolo indole analogs. These drugs
      irreversibly alkylate parasite DNA, blocking their ability to replicate. After
      administration in mice, DNA from the vaccine could be detected in the blood for
      over 110 days and a single vaccination induced profound immunity to different
      malaria parasite species. Immunity was mediated by CD4+ T cells and was dependent
      on the red blood cell membrane remaining intact. The human parasite, Plasmodium
      falciparum, could also be attenuated by treatment with seco-cyclopropyl pyrrolo
      indole analogs. These data demonstrate that vaccination with chemically
      attenuated parasites induces protective immunity and provide a compelling
      rationale for testing a blood-stage parasite-based vaccine targeting human
      Plasmodium species.

PMID- 23863623
TI  - Colon cancer progression is driven by APEX1-mediated upregulation of Jagged.
AB  - Aberrant expression of apurinic-apyrimidinic endonuclease-1 (APEX1) has been
      reported in numerous human solid tumors and is positively correlated with cancer
      progression; however, the role of APEX1 in tumor progression is poorly defined.
      Here, we show that APEX1 contributes to aggressive colon cancer behavior and
      functions as an upstream activator in the Jagged1/Notch signaling pathway. APEX1
      overexpression or knockdown in human colon cancer cell lines induced profound
      changes in malignant properties such as cell proliferation, anchorage-independent
      growth, migration, invasion, and angiogenesis in vitro and in tumor formation and
      metastasis in mouse xenograft models. These oncogenic effects of APEX1 were
      mediated by the upregulation of Jagged1, a major Notch ligand. Furthermore, APEX1
      expression was associated with Jagged1 in various colon cancer cell lines and in
      tissues from colon cancer patients. This finding identifies APEX1 as a positive
      regulator of Jagged1/Notch activity and suggests that it is a potential
      therapeutic target in colon cancers that exhibit high levels of Jagged1/Notch
      signaling.

PMID- 23863624
TI  - Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes.
AB  - Macrophages play a key role in responding to pathogens and initiate an
      inflammatory response to combat microbe multiplication. Deactivation of
      macrophages facilitates resolution of the inflammatory response. Deactivated
      macrophages are characterized by an immunosuppressive phenotype, but the lack of
      unique markers that can reliably identify these cells explains the poorly defined
      biological role of this macrophage subset. We identified lipocalin 2 (LCN2) as
      both a marker of deactivated macrophages and a macrophage deactivator. We show
      that LCN2 attenuated the early inflammatory response and impaired bacterial
      clearance, leading to impaired survival of mice suffering from pneumococcal
      pneumonia. LCN2 induced IL-10 formation by macrophages, skewing macrophage
      polarization in a STAT3-dependent manner. Pulmonary LCN2 levels were tremendously
      elevated during bacterial pneumonia in humans, and high LCN2 levels were
      indicative of a detrimental outcome from pneumonia with Gram-positive bacteria.
      Our data emphasize the importance of macrophage deactivation for the outcome of
      pneumococcal infections and highlight the role of LCN2 and IL-10 as determinants
      of macrophage performance in the respiratory tract. 

PMID- 23863625
TI  - Inactivation of specific beta cell transcription factors in type 2 diabetes.
AB  - Type 2 diabetes (T2DM) commonly arises from islet beta cell failure and insulin
      resistance. Here, we examined the sensitivity of key islet-enriched transcription
      factors to oxidative stress, a condition associated with beta cell dysfunction in
      both type 1 diabetes (T1DM) and T2DM. Hydrogen peroxide treatment of beta cell
      lines induced cytoplasmic translocation of MAFA and NKX6.1. In parallel, the
      ability of nuclear PDX1 to bind endogenous target gene promoters was also
      dramatically reduced, whereas the activity of other key beta cell transcriptional
      regulators was unaffected. MAFA levels were reduced, followed by a reduction in
      NKX6.1 upon development of hyperglycemia in db/db mice, a T2DM model. Transgenic
      expression of the glutathione peroxidase-1 antioxidant enzyme (GPX1) in db/db
      islet beta cells restored nuclear MAFA, nuclear NKX6.1, and beta cell function in
      vivo. Notably, the selective decrease in MAFA, NKX6.1, and PDX1 expression was
      found in human T2DM islets. MAFB, a MAFA-related transcription factor expressed
      in human beta cells, was also severely compromised. We propose that MAFA, MAFB,
      NKX6.1, and PDX1 activity provides a gauge of islet beta cell function, with loss
      of MAFA (and/or MAFB) representing an early indicator of beta cell inactivity and
      the subsequent deficit of more impactful NKX6.1 (and/or PDX1) resulting in overt
      dysfunction associated with T2DM. 

PMID- 23863626
TI  - Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient
      mice.
AB  - Platelets are anuclear organelle-rich cell fragments derived from bone marrow
      megakaryocytes (MKs) that safeguard vascular integrity. The major platelet
      organelles, alpha-granules, release proteins that participate in thrombus
      formation and hemostasis. Proteins stored in alpha-granules are also thought to
      play a role in inflammation and wound healing, but their functional significance
      in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet
      syndrome (GPS), a rare bleeding disorder characterized by macrothrombocytopenia,
      with platelets lacking alpha-granules. Here we show that Nbeal2-knockout mice
      display the characteristics of human GPS, with defective alpha-granule biogenesis
      in MKs and their absence from platelets. Nbeal2 deficiency did not affect MK
      differentiation and proplatelet formation in vitro or platelet life span in vivo.
      Nbeal2-deficient platelets displayed impaired adhesion, aggregation, and
      coagulant activity ex vivo that translated into defective arterial thrombus
      formation and protection from thrombo-inflammatory brain infarction following
      focal cerebral ischemia. In a model of excisional skin wound repair, Nbeal2
      deficient mice exhibited impaired development of functional granulation tissue
      due to severely reduced differentiation of myofibroblasts in the absence of alpha
      granule secretion. This study demonstrates that platelet alpha-granule
      constituents are critically required not only for hemostasis but also thrombosis,
      acute thrombo-inflammatory disease states, and tissue reconstitution after
      injury.

PMID- 23863627
TI  - Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid
      gene therapy.
AB  - For most lysosomal storage diseases (LSDs) affecting the CNS, there is currently
      no cure. The BBB, which limits the bioavailability of drugs administered
      systemically, and the short half-life of lysosomal enzymes, hamper the
      development of effective therapies. Mucopolysaccharidosis type IIIA (MPS IIIA) is
      an autosomic recessive LSD caused by a deficiency in sulfamidase, a sulfatase
      involved in the stepwise degradation of glycosaminoglycan (GAG) heparan sulfate.
      Here, we demonstrate that intracerebrospinal fluid (intra-CSF) administration of
      serotype 9 adenoassociated viral vectors (AAV9s) encoding sulfamidase corrects
      both CNS and somatic pathology in MPS IIIA mice. Following vector administration,
      enzymatic activity increased throughout the brain and in serum, leading to whole
      body correction of GAG accumulation and lysosomal pathology, normalization of
      behavioral deficits, and prolonged survival. To test this strategy in a larger
      animal, we treated beagle dogs using intracisternal or intracerebroventricular
      delivery. Administration of sulfamidase-encoding AAV9 resulted in transgenic
      expression throughout the CNS and liver and increased sulfamidase activity in
      CSF. High-titer serum antibodies against AAV9 only partially blocked CSF-mediated
      gene transfer to the brains of dogs. Consistently, anti-AAV antibody titers were
      lower in CSF than in serum collected from healthy and MPS IIIA-affected children.
      These results support the clinical translation of this approach for the treatment
      of MPS IIIA and other LSDs with CNS involvement.

PMID- 23863628
TI  - Neutrophil extracellular traps sequester circulating tumor cells and promote
      metastasis.
AB  - The majority of patients with cancer undergo at least one surgical procedure as
      part of their treatment. Severe postsurgical infection is associated with adverse
      oncologic outcomes; however, the mechanisms underlying this phenomenon are
      unclear. Emerging evidence suggests that neutrophils, which function as the first
      line of defense during infections, facilitate cancer progression. Neutrophil
      extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released
      in response to inflammatory cues that trap and kill invading pathogens. The role
      of NETs in cancer progression is entirely unknown. We report that circulating
      tumor cells become trapped within NETs in vitro under static and dynamic
      conditions. In a murine model of infection using cecal ligation and puncture, we
      demonstrated microvascular NET deposition and consequent trapping of circulating
      lung carcinoma cells within DNA webs. NET trapping was associated with increased
      formation of hepatic micrometastases at 48 hours and gross metastatic disease
      burden at 2 weeks following tumor cell injection. These effects were abrogated by
      NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings
      implicate NETs in the process of cancer metastasis in the context of systemic
      infection and identify NETs as potential therapeutic targets.

PMID- 23863629
TI  - Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis.
AB  - Septic shock is characterized by increased vascular permeability and hypotension
      despite increased cardiac output. Numerous vasoactive cytokines are upregulated
      during sepsis, including angiopoietin 2 (ANG2), which increases vascular
      permeability. Here we report that mice engineered to inducibly overexpress ANG2
      in the endothelium developed sepsis-like hemodynamic alterations, including
      systemic hypotension, increased cardiac output, and dilatory cardiomyopathy.
      Conversely, mice with cardiomyocyte-restricted ANG2 overexpression failed to
      develop hemodynamic alterations. Interestingly, the hemodynamic alterations
      associated with endothelial-specific overexpression of ANG2 and the loss of
      capillary-associated pericytes were reversed by intravenous injections of adeno
      associated viruses (AAVs) transducing cDNA for angiopoietin 1, a TIE2 ligand that
      antagonizes ANG2, or AAVs encoding PDGFB, a chemoattractant for pericytes. To
      confirm the role of ANG2 in sepsis, we i.p. injected LPS into C57BL/6J mice,
      which rapidly developed hypotension, acute pericyte loss, and increased vascular
      permeability. Importantly, ANG2 antibody treatment attenuated LPS-induced
      hemodynamic alterations and reduced the mortality rate at 36 hours from 95% to
      61%. These data indicate that ANG2-mediated microvascular disintegration
      contributes to septic shock and that inhibition of the ANG2/TIE2 interaction
      during sepsis is a potential therapeutic target.

PMID- 23863630
TI  - beta-globin gene transfer to human bone marrow for sickle cell disease.
AB  - Autologous hematopoietic stem cell gene therapy is an approach to treating sickle
      cell disease (SCD) patients that may result in lower morbidity than allogeneic
      transplantation. We examined the potential of a lentiviral vector (LV) (CCL
      betaAS3-FB) encoding a human hemoglobin (HBB) gene engineered to impede sickle
      hemoglobin polymerization (HBBAS3) to transduce human BM CD34+ cells from SCD
      donors and prevent sickling of red blood cells produced by in vitro
      differentiation. The CCL-betaAS3-FB LV transduced BM CD34+ cells from either
      healthy or SCD donors at similar levels, based on quantitative PCR and colony
      forming unit progenitor analysis. Consistent expression of HBBAS3 mRNA and HbAS3
      protein compromised a fourth of the total beta-globin-like transcripts and
      hemoglobin (Hb) tetramers. Upon deoxygenation, a lower percentage of HBBAS3
      transduced red blood cells exhibited sickling compared with mock-transduced cells
      from sickle donors. Transduced BM CD34+ cells were transplanted into
      immunodeficient mice, and the human cells recovered after 2-3 months were
      cultured for erythroid differentiation, which showed levels of HBBAS3 mRNA
      similar to those seen in the CD34+ cells that were directly differentiated in
      vitro. These results demonstrate that the CCL-betaAS3-FB LV is capable of
      efficient transfer and consistent expression of an effective anti-sickling beta
      globin gene in human SCD BM CD34+ progenitor cells, improving physiologic
      parameters of the resulting red blood cells.

PMID- 23863631
TI  - Chronic THC intake modifies fundamental cerebellar functions.
AB  - Delta9-tetrahydrocannabinol (THC), the principal bioactive component in the
      Cannabis plant, is truly a captivating drug. Acute and chronic THC intake
      produces a spectrum of biological effects ranging from transient psychotropic
      effects to prolonged medicinal benefits, many of which have been fostered for
      centuries by our society. In the July 2013 issue of the JCI, Cutando et al.
      combined mouse genetics with classic mouse behavioral analysis to deepen our
      understanding of the physiological consequence of subchronic THC intake on
      eyeblink reflexes, a fundamental neuronal adaptive response, revealing that this
      regimen leads to downregulation of the cannabinoid CB1 receptor (referred to as
      CB1 in the Cutando et al. article) in cerebellar stress fibers and the activation
      of microglia, raising provocative new questions about the safety profile of
      regimented THC intake.

PMID- 23863632
TI  - A conversation with Christine Seidman. Interview by Ushma S. Neill.

PMID- 23863633
TI  - Radiation and immunotherapy: a synergistic combination.
AB  - Immunotherapy can be an effective treatment for metastatic cancer, but a
      significant subpopulation will not respond, likely due to the lack of antigenic
      mutations or the immune-evasive properties of cancer. Likewise, radiation therapy
      (RT) is an established cancer treatment, but local failures still occur. Clinical
      observations suggest that RT may expand the therapeutic reach of immunotherapy.
      We examine the immunobiologic and clinical rationale for combining RT and
      immunotherapy, two modalities yet to be used in combination in routine practice.
      Preclinical data indicate that RT can potentiate the systemic efficacy of
      immunotherapy, while activation of the innate and adaptive immune system can
      enhance the local efficacy of RT. 

PMID- 23863635
TI  - Antiinflammatory effects of apoptotic cells.
AB  - Apoptotic cells are rapidly phagocytosed by macrophages, a process that
      represents a critical step in tissue remodeling, immune responses, and the
      resolution of inflammation. In 1998, Peter Henson, Donna Bratton, and colleagues
      at National Jewish Health demonstrated that phagocytosis of apoptotic cells
      actively suppresses inflammation by inhibiting the production of inflammatory
      cytokines and inducing production of antiinflammatory factors, including TGF-beta
      and prostaglandin E2. Here they discuss the evolving relationship among
      apoptosis, phagocytosis, and inflammation. 

PMID- 23863640
TI  - The inextricable relationship of emergency care, national health
      security/preparedness, and health care reform.

PMID- 23863634
TI  - AMPK, insulin resistance, and the metabolic syndrome.
AB  - Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic
      syndrome, as are central adiposity, dyslipidemia, and a predisposition to type 2
      diabetes, atherosclerotic cardiovascular disease, hypertension, and certain
      cancers. Regular exercise and calorie restriction have long been known to
      increase insulin sensitivity and decrease the prevalence of these disorders. The
      subsequent identification of AMP-activated protein kinase (AMPK) and its
      activation by exercise and fuel deprivation have led to studies of the effects of
      AMPK on both IR and metabolic syndrome-related diseases. In this review, we
      evaluate this body of literature, with special emphasis on the hypothesis that
      dysregulation of AMPK is both a pathogenic factor for these disorders in humans
      and a target for their prevention and therapy. 

PMID- 23863641
TI  - The role of the aversive effects of drugs in self-administration: assessing the
      balance of reward and aversion in drug-taking behavior.
AB  - Since the first experimental demonstration that a drug of abuse supports
      instrumental behavior, drugs have been discussed in the context of their
      rewarding effects, which are assumed to drive and maintain drug-taking behavior.
      Indeed, drug reward has been fundamental in the formulation of most models of
      drug use, abuse, and addiction. Over the last several decades, however, drugs of
      abuse have been increasingly recognized as complex pharmacological compounds
      producing multiple stimulus effects, not all of which are rewarding. The aversive
      effects of such drugs, for example, have been described by a number of
      researchers working in the field, although few attempts have been made to
      investigate the role of these aversive effects in drug taking. The present paper
      offers a historical perspective on the view that drugs of abuse are complex
      pharmacological compounds with multiple stimulus effects. In doing so, we argue
      that the discussion of drug reward only may be insufficient in accounting for
      drug taking and we present evidence for the theoretical position that both the
      rewarding and the aversive effects of drugs should be taken into consideration in
      ongoing attempts to model drug-taking behavior. The present review summarizes
      several decades of research characterizing the aversive effects of major drugs of
      abuse, as well as more recent studies seeking to assess directly the role of drug
      aversion in drug taking. 

PMID- 23863642
TI  - [Induction chemotherapy for solid tumors].
AB  - Surgical treatment for solid malignancies, which is the gold standard for
      operable tumors, is being combined with nonsurgical modalities with an increasing
      frequency. Advanced cancers that are not curable by surgery alone are subjected
      to sophisticated multimodality regimens. Accordingly, the sequence and timing of
      integrated combined treatment modalities are essential. Traditionally, the common
      objective of induction chemotherapy has been to reduce the risk of distant
      disease recurrence. Administration of chemotherapy before other treatment has
      many theoretical advantages. Induction chemotherapy can result in tumor
      downstaging, thus increasing the rate of conservative surgery. In cases of more
      advanced disease, induction chemotherapy can render inoperable tumors resectable.
      Other advantages of induction chemotherapy include the ability to obtain
      information about tumor response, which can be used to study the biologic effects
      of chemotherapy and assess long-term disease-free survival(DFS)and overall
      survival(OS). Induction chemotherapy as a component of primary treatment has been
      shown in several studies and meta-analyses to decrease the incidence of
      metastatic disease. Currently, the terms induction, primary, preoperative, basal
      and neoadjuvant are all used to describe chemotherapy given as initial treatment.
      There are 2 methods of induction chemotherapy: intra-arterial induction
      chemotherapy and induction systemic chemotherapy. The clinical results of several
      trials of arterial infusion chemotherapy alone as induction chemotherapy for
      advanced cancer revealed that 20-30% higher response rates can be achieved.
      However, the benefits of prolonged survival rates and improved quality of life
      are not consistently realized. Induction arterial infusion chemotherapy did not
      gain enthusiastic support for several different malignancies. Induction systemic
      chemotherapy is mainly used in patients with stage II/III disease to improve
      surgical outcomes and increase the rate of breast-conserving surgery in the
      breast cancer case, although clinical studies have not revealed a significant
      improvement in DFS or OS. The favorable response rate and achievement of
      pathological complete response(pCR)have favorable effects on DFS in breast cancer
      patients. The available data suggest a minimal benefit for additional
      chemotherapy after surgery in patients with residual disease. New targets must be
      identified to develop non-cross-resistant agents for patients with residual
      disease after prior chemotherapy. New genomic and proteomic tools must be
      developed to identify predictive markers for response to primary systemic therapy
      that allow clinicians to develop more personalized therapy, new strategic
      options, and new biologic agents and avoid unnecessary regimens. The side effects
      of induction chemotherapy depend on the types of drugs, their doses, and the
      duration of treatment. 

PMID- 23863643
TI  - [Pathophysiology and diagnosis of cancer patients with febrile neutropenia].
AB  - Exogenous pyrogens induce several cytokines which activate immune responses, and
      produce fever. In Japan, febrile neutropenia is defined as having an axillary
      temperature of>37. 5 degrees C, and neutropenia showing an absolute neutrophil
      count (ANC)of<500 cells/mL or an ANC that is expected to reduce to<500 cells/mL
      during the next 48 hours. Signs and symptoms of inflammation are often attenuated
      or absent in neutropenic patients. Therefore, careful physical examination is
      required to detect subtle symptoms and signs of infection. As an initial
      assessment, laboratory tests should include the following: a ) complete blood
      cell count with differential leukocyte count and platelet count, b ) measurement
      of serum levels of creatinine, electrolytes, and hepatic transaminase enzymes, c
      ) serologic assay for fungal infection, and d ) at least 2 sets of blood
      cultures. Radiographical approaches are also important for detecting the focus of
      infection. Proper risk classification should be performed using the Multinational
      Association for Supportive Care in Cancer(MASCC)scoring system to distinguish
      high-risk and low-risk patients with febrile neutropenia. 

PMID- 23863644
TI  - [Strategies of treatment for febrile neutropenia].
AB  - The guideline on febrile neutropenia(FN)was published by the Japanese Society of
      Medical Oncology(JSMO)in 2012. Based on this guideline, the treatment strategy
      for febrile neutropenia that is discussed in this paper includes empiric
      treatment strategies, methicillin-resistant Staphylococcus aureus antibiotics in
      the initial treatment, treatment for severe FN, treatment for outpatients,
      duration of FN treatment, treatment after recovery from fever associated with
      neutropenia, and empiric treatment with anti-fungal drugs in patients with
      prolonged FN. 

PMID- 23863645
TI  - [Tips on the use of granulocyte colony-stimulating factors in cancer patients
      predisposed to chemotherapy - induced febrile neutropenia].
AB  - Chemotherapy-induced febrile neutropenia(FN)is a major risk factor for severe
      infections, with a dose-limiting toxicity that necessitates dose reductions
      and/or delays in scheduled chemotherapy sessions. Therefore, the use of
      granulocyte colony- stimulating factors(G-CSF)is recommended in cancer patients
      at a risk of chemotherapy-induced FN. Three types of GCSF, filgrastim,
      lenograstim, and nartograstim, have been available thus far. The differences in
      potency and efficacy among these G-CSF needs to be thoroughly understood.
      Prophylactic G-CSF is recommended in patients receiving a chemotherapy regimen
      associated with a high risk(>20%)of FN. A chemotherapy regimen associated with
      intermediate risk(10-20%)of FN, requires particular attention to the neutrophil
      count and observation of symptoms of infection after chemotherapy. Prophylactic G
      CSF could be included in subsequent chemotherapy regimens, if needed. 

PMID- 23863646
TI  - [A general description of the clinical guideline for the management of febrile
      neutropenia].
AB  - The most serious adverse event in cancer patients who receive anti-neoplastic
      agents is febrile neutropenia(FN). The clinical guideline for the use of
      antimicrobial agents in managing patients with FN was published by the Infectious
      Diseases Society of America. However, the dosage and administration of
      antimicrobial agents are not completely adapted for Japanese insurance coverage.
      The Japanese Society of Medical Oncology therefore decided to develop a clinical
      guideline for the management of FN in Japanese patients. In this study, we
      provide a general description of the guideline. According to the guideline, fever
      is defined as a single axillary temperature of B37. 5 degrees C(or an oral
      temperature of B38 degrees C)and neutropenia is defined as a neutrophil count of
      <500/mL or <1, 000/mL if the count is expected to decrease to <500/mL within the
      next 48 h. In patients who develop FN, empirical anti-pseudomonal b-lactam agent
      monotherapy should be administered promptly at the onset of fever. Antibiotic
      therapy should continue until patients become afebrile and their neutrophil
      counts recover to B500/mL. If fever persists for 4-7 days under antibiotic
      therapy in high-risk patients, empirical antifungal therapy should be considered.
      Granulocyte colony-stimulating factor prophylaxis should be considered for high
      risk patients with an anticipated risk of FN of B20%. 

PMID- 23863647
TI  - [Outcomes of advanced gastric cancer patients treated with chemoradiation
      therapy].
AB  - We retrospectively analyzed 20 patients with advanced gastric cancer treated with
      chemoradiation(CRT). The patients consisted of 16 males and 4 females, 17(85%)of
      whom received intensive chemotherapy prior to CRT. Radiation was administered
      concurrently at 40 to 55 Gy according to the purpose of treatment. Sixteen
      patients received low dose CDDP and S-1. Of 8 patients who had measurable
      disease, one obtained CR and 3 obtained PR by the CRT. Fifteen percent of the
      distinct adverse effects of CRT were grade 3 leucopenia and 30% of them were
      grade 3 nausea. The 2-year-survival of patients who received CRT with curative
      intent was 91%, significantly higher than the percentage of those with palliative
      intent. Four patients who received R0 surgery following CRT are postoperatively
      healthy without symptoms of relapse. In conclusion, even though, 75% of the
      patients were already given chemotherapy prior to CRT, good outcomes were
      achieved unexpectedly. The combination of CRT and surgery may be a useful tool
      for chemo-resistant, locally advanced gastric cancer. 

PMID- 23863648
TI  - [Comparative study of an antiemetic NK1 receptor-antagonist in lung cancer
      patients treated with divided doses for Cisplatin].
AB  - Aprepitant is a NK1 receptor-antagonist with a novel mechanism of action for
      chemotherapy-induced nausea and vomiting (CINV), and is recommended as a
      prophylactic by many international and domestic guidelines. However, domestic
      clinical trials of aprepitant have only been conducted using a single dose in
      patients who were treated with cisplatin(CDDP), and there is no evidence to
      support administration of aprepitant in divided doses. We administered aprepitant
      in divided doses to patients who were also being treated with cisplatin,
      ifosfamide, and irinotecan(CIC), and had CINV due to prophylactic administration
      of a 5-HT3 receptor antagonist and dexamethasone. This was done in order to
      evaluate the antiemetic effect of aprepitant. The patients with"No
      vomiting"increased significantly from 25% to 83%, and the"Days with nausea"in
      patients also decreased significantly. Consequently, administration of aprepitant
      in addition to current antiemetic therapy in divided doses, as well as in single
      doses, exhibited a greater antiemetic effect in CDDP-treated patients. 

PMID- 23863649
TI  - [Clinical efficacy and safety assessment of eribulin monotherapy in patients with
      metastatic breast cancer - a single- institute experience].
AB  - Eribulin mesylate, a novel microtubule inhibitor with a unique mechanism of
      action, was approved in Japan in April 2011 for the treatment of metastatic
      breast cancer patients who had been administered at least two prior
      chemotherapeutic agents. Here, we present a retrospective review of data from 27
      patients who received eribulin monotherapy in our hospital. The overall response
      rate and clinical benefit rate were 25. 9% and 29. 6%, respectively, and the
      median progression-free survival was 9. 9 weeks(95% CI: 3. 5-16. 2 weeks). The
      toxicities of treatment were tolerable and manageable; responses were lower in
      patients who were triple negative subtype, and higher in patients who had
      responded to prior taxane treatment. The relative dose intensity of our data
      indicates that appropriate modification of dose and schedule may be an important
      part of eribulin monotherapy. 

PMID- 23863650
TI  - [Magnesium premedication prevents Cisplatin-induced nephrotoxicity in patients
      with esophageal and hypopharyngeal cancer].
AB  - Hypomagnesemia is one of the well-known side effects in patients receiving
      cisplatin-containing chemotherapy. However, the relevance between hypomagnesemia
      and cisplatin-induced nephrotoxicity remain to be completely elucidated. Although
      patients with esophageal and hypopharyngeal cancer are susceptible to
      dehydration, there is no evidence yet that magnesium supplementation for these
      patients will prevent nephrotoxicity during cisplatin-containing chemotherapy.
      The aim of this study was to examine the effect of magnesium supplementation on
      the prevention of cisplatin-induced nephrotoxicity for patients with esophageal
      and hypopharyngeal cancer. Twenty-three patients with esophageal or
      hypopharyngeal cancer were studied over 2 weeks. Ten of them received magnesium
      supplementation and 13 did not. Magnesium sulphate(20 mEq) was administered
      before 5-fluorouracil(800mg/m2/24 h/day 1-5)and cisplatin(80mg/m2/day
      1)(FP)treatment. The maximum serum creatinine concentration of magnesium
      supplemented group demonstrated a significantly lower concentration compared to
      the non-magnesium-supplemented group(p=0. 018). As a result, magnesium
      supplementation successfully reduced the incidence rate of nephrotoxicity(p=0.
      038). These results showed that magnesium supplementation before FP treatment may
      be quite beneficial for preventing nephrotoxicity in patients with esophageal and
      hypopharyngeal cancer, and it is therefore recommended that magnesium be
      routinely supplemented during FP treatment for esophageal or hypopharyngeal
      cancer. 

PMID- 23863652
TI  - [Comparison of HER2 immunohistochemical results for advanced gastric cancer
      obtained on using 3 different antibodies].
AB  - We compared the results of immunohistochemical assessment of HER2 expression in
      107 samples of advanced gastric cancer on using 3 currently used antibodies.
      Expression was scored as 0 to 3+, and equivocal or discordant cases were
      subjected to fluorescence in situ hybridization(FISH)analysis. HER2 scores of
      2+or 3+were noted in 16.8% of cases(18/ 107)using SV2-61g, in 29.9% of
      cases(32/107)using Dako HercepTest, and in 34.6% of cases(37/107)using 4B5. The
      results of the HER2 test differed according to the antibodies used for
      immunohistochemistry preceding FISH analysis, and the HER2 positive rates after
      the FISH analysis were 14.0%(15/107)using SV2-61g, 19.6% (21/107)using Dako
      HercepTest, and 22.4% (24/107)using 4B5. Thus, therapeutic decisions might be
      considerably influenced by the antibody used for the HER2 test. 

PMID- 23863651
TI  - Phase II clinical trial of high-dose toremifene as primary hormone therapy in
      aromatase inhibitor-resistant breast cancer.
AB  - BACKGROUND: Third-generation aromatase inhibitors(AIs)are now common in adjuvant
      hormone therapy for breast cancer in postmenopausal women. However, a suitable
      treatment has yet to be established for patients who develop cancer recurrence
      during or after adjuvant AI therapy. PATIENTS AND METHODS: This prospective study
      evaluated the efficacy and safety of 120mg/day toremifene citrate(TOR
      120)administered orally to 23 patients with recurrent breast cancer who were
      receiving or had received adjuvant AI therapy. Primary therapy for recurrence was
      TOR-120 monotherapy. RESULTS: The response rate was 13. 0%(partial response:
      three patients), the clinical benefit rate was 78. 3%(partial response: three
      patients; long-term stable disease: 15 patients), and median time to progression
      was 8. 1 months. Grade 1 adverse events such as loss of appetite, sweating,
      flushing and edema face were observed. CONCLUSION: TOR-120 monotherapy was
      effective and safe as a primary hormone therapy for recurrent breast cancer
      unresponsive to AIs.

PMID- 23863653
TI  - [Usefulness of bevacizumab with paclitaxel for advanced breast cancer - a case
      report].
AB  - A 55-year-old woman with an exudative, necrotizing left breast tumor consulted
      Ibaraki Prefectural Central Hospital and Cancer Center. We diagnosed her as
      advanced ER+, PgR-, HER2- invasive ductal carcinoma of the left breast by tumor
      needle biopsy. FDG-PET/CT revealed multiple lymph node, pulmonary, bone, and
      hepatic metastases. Systemic chemotherapy with biweekly bevacizumab and weekly
      paclitaxel(PTX)was administered. The chemotherapy induced a widespread tumor
      lysis in her left chest wall. We continued chemotherapy, and the ulcer has been
      healing gradually. We recognized that bevacizumab with PTX successfully brought
      about a rapid, good local response, and improved the patient's quality of life. 

PMID- 23863654
TI  - [A case of a patient with breast cancer, diagnosed from sternal metastasis].
AB  - A 32-year-old woman was seen in our hospital for complaints of bulge and pain in
      the sternum, and upon examination showed a lump in the left breast and enlarged
      left axillary lymph nodes. The patient was diagnosed with invasive ductal
      carcinoma with metastasis to the sternum that was T2N1M1(OSS), Stage IV, hormone
      receptor-positive, and HER2-negative. Four courses each of EC and taxane therapy
      were performed as primary systemic chemotherapy in combination with zoledronic
      acid, which resulted in calcification of the osteolytic lesion in the sternum and
      reduced tumor mass in the breast. The patient was judged to have a partial
      response(PR)to the treatment. Eight months later, breast-conserving surgery and
      axillary lymph node dissection were performed, followed by radiation therapy to
      the left breast and sternum. Treatment with zoledronicac id is ongoing and
      postoperative hormonal therapy has been started. Four years and 4 months after
      the initial diagnosis, the lesion in the sternum has calcified and hardened and
      the patient has not had a recurrence in the same breast or elsewhere in the body.

PMID- 23863655
TI  - [Two cases of multiple liver metastases breast cancer successfully treated with
      combination chemotherapy by S-1, vinorelbine and medroxyprogesterone].
AB  - We report our experience with two cases of postoperative multiple liver
      metastases that were reduced remarkably by S-1, VNR, and MPA combination therapy
      for breast cancer. A case diagnosed as Stage II B(T2, N1, M0)breast cancer was
      treated postoperatively with LH-RH agonist and TAM. Another case, diagnosed as
      Stage III B(T4b, N2, M0), was treated with postoperative CE therapy. Tumor
      markers were normalized and liver metastases were shrunk significantly in both
      cases which received combination chemotherapy of S-1, VNR, and MPA as first-line
      therapy after recurrence. We conclude that this combination chemotherapy is a
      useful regimen for metastatic breast cancer patients, because it can be
      continuously implemented over a long period of time while maintaining high QOL
      without serious adverse events. 

PMID- 23863657
TI  - [A case of metastatic small intestinal tumor from primary lung cancer with
      hemorrhage and a high G-CSF serum level].
AB  - A 83-year-old man presented at our hospital with hemosputum, and Stage III
      B(T4N3M0)lung cancer was diagnosed after thorough examinations. Although systemic
      chemotherapy was performed and kept the disease stable, anemia progressed. The
      fecal occult blood was recognized, and the enhanced abdominal CT scan revealed a
      8 cm enhanced small intestinal tumor. Laboratory data indicated the presence of
      an inflammatory reaction(WBC 17, 970/mm3, CRP 1.38 mg/dL), and the serum
      granulocyte-colony stimulating factor(G-CSF)was elevated(104.0 pg/mL). A small
      intestinal tumor with hemorrhage and G-CSF production was diagnosed, and
      laparoscopy-assisted partial resection of the small intestine was performed. On
      histopathologic and immunohistochemical findings, the intestinal tumor was
      diagnosed as a small bowel metastasis originating from a primary lung cancer.
      After surgery, anemia progression stopped and WBC kept at a normal range.
      Although systemic chemotherapy was resumed because of performance status
      improvement, the disease progressed gradually. The patient received best
      supportive care and died about 9 months after the diagnosis of small bowel
      metastasis. 

PMID- 23863656
TI  - [Successful ventilator weaning by trastuzumab in a HER2-positive breast cancer
      patient with multiple lung metastases].
AB  - We report a case of breast cancer with severe respiratory dysfunction due to
      multiple lung metastases, which was recovered by treatment with weekly
      trastuzumab administration. A 47-year-old woman with breast cancer had received a
      folk remedy from a general practitioner for 4 years. However, she was delivered
      to a hospital because of severe dyspnea, and intubation was found to be needed
      and performed. She was diagnosed with left breast cancer with skin and pleural
      wall invasion, and multiple lung metastases. Pathological examination showed
      invasive ductal carcinoma which was ER-postive, PgR-negative, and HER2-postive.
      After transfer to our hospital, treatment with trastuzumab(4mg/kg/weekly for the
      first course, and 2 mg/kg/weekly thereafter)was administered. Respiratory
      function improved gradually, and ventilator weaning was successful at 53 days
      after trastuzumab administration. CT examination also showed a remarkable
      reduction of lung and lymph node metastases and pleural effusion. She was
      discharged from our hospital 80 days after treatment, and her treatment with
      trastuzumab and capecitabine has been ongoing at an outpatient clinic. 

PMID- 23863658
TI  - [A case of lung cancer resistant to pemetrexed responding to S-1 monotherapy].
AB  - Pemetrexed(PEM)and S-1 are both cytotoxic anti-tumor drugs that target
      thymidylate synthase(TS). Here, we report a case of lung cancer resistant to PEM,
      but responsive to S-1 monotherapy. A 50-year-old male with lung
      cancer(adenocarcinoma, EGFR mutation negative)at Stage III B(T4N2M0)received PEM
      as third-line chemotherapy. However, metastatic mediastinal lymph nodes were
      increased in size. A switch to gemcitabine(GEM)resulted in further enlargement of
      the nodes and elevation of the serum CEA level. Introduction of S-1
      monotherapy(120mg/body/day divided into two doses, 4-week administration every 6
      weeks, 6 courses)reduced the size of the nodes and serum CEA was normalized.
      Although S-1 as well as PEM, target TS, the mechanisms in these two drugs that
      lead to resistance are not the same. Furthermore, S-1 induces dysfunction of RNA
      through the generation of fluoro-uridine monophosphate(FUMP). We conclude that S
      1 can be a drug of choice, even in cases that show resistance to PEM. 

PMID- 23863659
TI  - [A case of pancreatic body cancer with multiple liver metastases experiencing
      long-term response by gemcitabine plus erlotinib therapy].
AB  - We report a case of pancreatic body cancer with multiple liver metastases whose
      response duration was 295 days in a Japanese phase II trial of
      gemcitabine(GEM)plus erlotinib. The patient was a 64-year-old male. He visited
      our hospital with the main complaint of epigastralgia and weight loss in May,
      2007, and was diagnosed as advanced pancreatic cancer with abdominal paraaortic
      lymph node metastasis and liver metastases(Stage IV)by abdominal computed
      tomography and percutaneous biopsy of liver metastases. Partial response(PR)was
      found at the end of the sixth course of GEM+erlotinib, and his serum
      concentration of CA19-9 remarkably decreased. PR continued for a long period
      until a new lesion was found at the initiation of the seventeenth course. This
      result suggests that GEM+erlotinib may provide long-term survival for pancreatic
      cancer patients with distant metastases. 

PMID- 23863660
TI  - [An autopsy of G-CSF-producing anaplastic carcinoma of the pancreas with impaired
      accumulation on FDG-PET after S-1 chemotherapy].
AB  - This paper presents a woman in her 70's with G-CSF producing anaplastic carcinoma
      of the pancreas(Stage IVb)who underwent chemotherapy by S-1 alone. On FDG-PET
      after the first course, accumulation of FDG was impaired remarkably. After the
      second course, the patient died of carcinomatous pleuritis and peritonitis on the
      88th day after initiation of treatment. G-CSF producing anaplastic carcinoma of
      the pancreas is extremely rare and there are no reports with regard to response
      evaluation by FDG-PET. Thus, this case has significant clinical value. 

PMID- 23863661
TI  - [A case of advanced gastric cancer with bulky lymph node metastases responding to
      S-1/CDDP neoadjuvant chemotherapy and leading to less invasive surgery and a
      pathologically complete response].
AB  - A 53-year-old man was diagnosed with advanced gastric cancer(cT4aN2M0, StageIII
      B), with regional bulky lymph node metastases invading the splenic artery. S-1
      plus cisplatin treatment(S-1/CDDP)was administered as neoadjuvant chemo-
      therapy(NAC). S-1(80mg/m2)was administered orally for 21 days, followed by 14
      drug-free days as a course. CDDP(60 mg/m2)was administered by intravenous drip on
      day 8. After two courses, significant tumor reduction was obtained, and the
      patient then had total gastrectomy and splenectomy performed with a D2
      dissection. Distal pancreatectomy was avoided. Macroscopically, the stomach
      seemed to be penetrated by the tumor into the serosa, yet the histological
      diagnosis revealed complete disappearance of cancer cells in all of the lymph
      nodes, and very few residual tumor cells were noted, only on the gastric
      mucosa(pT1aN0M0, Stage I A). Therefore, downstaging was confirmed. S-1/CDDP as a
      NAC regimen for advanced gastric cancer appears to be an effective treatment. 

PMID- 23863662
TI  - [A case of gastric adenosquamous carcinoma producing granulocyte-colony
      stimulating factor].
AB  - We report a case of gastric adenosquamous carcinoma producing granulocyte-colony
      stimulating factor (G-CSF). A 60- year-old man was admitted to our hospital
      complaining of upper abdominal pain. Endoscopic examination revealed a large type
      5 advanced gastric cancer with bleeding from the low body of stomach to the
      antrum, accompanied with para-aortic and mesenteric lymph node metastasis. He had
      marked leukocytosis, and serum levels of G-CSF were elevated. Histological
      diagnosis of the biopsy specimen was adenosquamous carcinoma producing G-CSF. We
      attempted combination chemotherapy with docetaxel, cisplatin and S-1(DCS). After
      1 course of treatment, the primary lesion was reduced in size. However, the size
      of the metastatic lymph node was larger. Chemotherapy was not effective enough,
      and the patient died 3 months after ending chemotherapy. 

PMID- 23863663
TI  - [Two cases of recurrent GIST successfully treated with imatinib mesylate at
      100mg/day].
AB  - Case 1: Recurrent tumors from gastric GIST in the liver and the abdominal wall
      showed partial response with 200mg/day imatinib and maintained partial response
      at 100mg/day. Case 2: Metastatic liver tumors from the jejunal GIST showed
      partial response with 200mg/day imatinib. The tumors have been enlarged for
      interruption of imatinib administration, however, re- treatment with imatinib
      resulted in partial response again and kept partial response at 100mg/day of
      imatinib. The two cases seldom encountered adverse events at 100mg/day of
      imatinib. There are some cases successfully treated with low-dose imatinib
      mesylate for recurrent GIST. 

PMID- 23863664
TI  - [A case of metastatic colon cancer effectively treated by XELOX and IRIS].
AB  - The patient was a 78-year-old woman who suffered from right upper quadrant pain.
      She was diagnosed as colon cancer with hepatic metastasis. Initial chemotherapy
      using capecitabine plus oxaliplatin(XELOX)+bevacizumab achieved partial response.
      After 12 months, XELOX was discontinued due to Grade 3 hand-foot syndrome and
      peripheral neuropathy. Irinotecan plus oral S-1(a combination of tegafur, 5
      chloro-2, 4-dihydroxypyridine, and potassium oxonate)and(IRIS)+bevacizumab were
      continued as second-line therapy, and her status was maintained as stable
      disease. XELOX and IRIS regimens do not require catheter placement and long
      infusion process, providing a great advantage to patients. 

PMID- 23863665
TI  - [A patient continued anti-cancer treatment because of effective colostomy against
      pain with defecation by local recurrence of rectal cancer].
AB  - A 60-year-old woman underwent a low anterior resection advanced rectal
      adenocarcinoma(Stage III a). Despite adjuvant therapy, liver metastasis and local
      recurrence appeared. Chemotherapy and radiotherapy were performed, nevertheless,
      the medical condition progressed, and pain with defecation by local recurrence
      appeared. The pain became resistant to the treatment due to non-opioid and opioid
      analgesics, and her quality of life(QOL)was gradually reduced. Transverse
      colostomy was performed as a palliative surgery to eliminate any contact
      stimulations during defecation. After surgery, pain improved, analgesics were no
      longer needed, and anti-cancer therapy was resumed. Palliative surgery should be
      considered for cancer pain resistant to drug therapy, if the trigger factors of
      pain can be expected to be removed. 

PMID- 23863666
TI  - [Successful management using laparoscopic splenectomy for splenomegaly and
      thrombocytopenia caused by oxaliplatin-based chemotherapy for advanced rectal
      cancer].
AB  - We report a case of advanced rectal cancer treated with chemotherapy, for which
      laparoscopic splenectomy had been effective for thrombocytopenia. A 56-year-old
      man suffered from advanced rectal cancer with multiple lung metastases. He
      underwent Hartmann's procedure and received chemotherapy with FOLFOX and FOLFIRI
      with bevacizumab. After 3 years and 2 months, he also suffered from splenomegaly
      and thrombocytopenia. Laparoscopic splenectomy produced and increased the
      thrombocyte count, allowing for a restart of chemotherapy. Oxaliplatin-based
      chemotherapy might produce hepatic sinusoid injury and induce splenomegaly owing
      to portal hypertension. Laparoscopic splenectomy seemed to be useful for treating
      thrombocytopenia, and allowed the continuation of chemotherapy. 

PMID- 23863667
TI  - [Survey of current status of adverse ocular reactions to paclitaxel and a
      retrospective analysis for aiding in early detection of adverse reactions].
AB  - We have observed several cases of adverse reactions to paclitaxel, including
      visual impairment and lacrimation. Therefore, we conducted a survey of the
      current status of adverse reactions to paclitaxel and also performed a
      retrospective analysis of the initial symptoms and the times of their appearance.
      Of the 22 study patients, 8(36. 4%)presented with adverse ocular reactions, such
      as visual impairment and lacrimation, and for 3(13. 6%), an ophthalmologist
      confirmed that paclitaxel could not be ruled out as the direct cause of their
      adverse reactions. The group of patients who presented with adverse ocular
      reactions included significantly more patients with ocular complications and a
      previous history of ocular ailments, compared to the group showing no such
      reactions. The timing of reaction appearance did not show a consistent pattern.
      The results of this study suggest that the initial symptoms were mainly visual
      impairment and lacrimation, and that caution must be taken when administering
      paclitaxel to patients with a previous history of ocular ailments and ocular
      complications because of the risk of adverse ocular reactions. Thus, adverse
      ocular reactions to paclitaxel were indicated as a possible risk, in addition to
      other adverse events such as myelosuppression and peripheral neuropathy. 

PMID- 23863668
TI  - [Role of hepatic arterial infusion chemotherapy in the treatment of colorectal
      cancer liver metastases].

PMID- 23863669
TI  - [Expression and survival prediction of microRNA-155 in hepatocellular carcinoma
      after liver transplantation].
AB  - OBJECTIVE: To explore the expression of microRNA-155 in hepatocellular carcinoma
      (HCC) and its contribution to recurrence and prognosis of HCC after liver
      transplantation (LT). METHODS: The expression levels of microRNA-155 in 100 HCC
      samples were detected by quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR). Kaplan-Meier and Cox proportional regression analyses were
      utilized to determine the association of microRNA-155 expression with patient
      survivals. RESULTS: The expression levels of microRNA-155 were higher in primary
      HCC patients with post-LT recurrence (n = 45, mean relative level = 14.94) than
      those with non-recurrence (n = 55, mean relative level = 4.70) (P = 0.001) and
      correlated with micro-vascular invasion of HCC tissue samples (P = 0.001). The
      patients with a higher expression of microRNA-155 had significantly worse
      recurrence-free survival (RFS: (21.5 +/- 3.2) months, log rank P < 0.001) and
      overall survival (OS: (29.3 +/- 3.2) months, log rank P < 0.001) than those with
      a lower expression of microRNA-155 (RFS: (50.8 +/- 3.2) months; OS: (54.6 +/-
      3.5) months). Multivariate analysis revealed that a high expression of miR-155
      was an independent prognostic predictor. CONCLUSION: MicroRNA-155 is over
      expressed in primary HCC with tumor recurrence and may serve as a novel biomarker
      for tumor recurrence and survival of HCC patients after LT. The detection of
      microRNA-155 is of clinical significance in HCC.

PMID- 23863670
TI  - [Expression of miRNA-29b and its clinical significances in primary hepatic
      carcinoma].
AB  - OBJECTIVE: To explore the clinical value of miRNA-29b expression and the combined
      detection of serum miRNA-29b and alpha-fetoprotein (AFP) in the diagnosis of
      primary hepatic carcinoma(PHC). METHODS: From January 2007 to May 2010, the serum
      levels of miRNA-29b and AFP from 96 healthy controls and 87 PHC patients were
      measured by quantitative reverse transcription-polymerase chain reaction (qRT
      PCR) and enzyme-linked immunosorbent assay (ELISA) respectively. The relationship
      of miRNA-29b and various clinical parameters was analyzed. RESULTS: Serum levels
      of miRNA-29b in PHC pre-operative group (0.250 (0.124 - 0.381)) significantly
      decreased versus the control group [0.860 (0.587 - 1.338)] and the post-operative
      group (0.890 (0.637 - 1.414)) (P < 0.001). Also, the levels of AFP in PHC pre
      operative group (65.4 (20.1 - 212.3)) was obviously higher than that in the
      control group (13.3 (7.1 - 19.8)) and the post-operative group (23.2 (11.6 -
      55.7)) (P < 0.001). A lower expression of miRNA-29b was correlated with lower
      differentiation and higher TNM stages (P < 0.045, P < 0.001). Kaplan-Meier curve
      analysis revealed that PHC patients with a low serum expression of miRNA-29b had
      a significantly shortened overall survival when compared with a high serum
      expression of miRNA-29b (25.52 vs 36.94 months, P = 0.008). Multivariable Cox
      regression analysis indicated that the serum expression of miRNA-29b was an
      independent risk factor for overall survival. Relative risk was 0.482 (95%
      confidence interval: 0.236 - 0.985). The critical values for miRNA-29b and AFP
      were determined at 0.38 and 23.1 ug/L through the ROC curves. Under the critical
      value, the sensitivity of miRNA-29b and AFP were 75.9% and 70.1% and the
      specificity of miRNA-29b and AFP 89.5% and 92.7% respectively. Combined detection
      could increase the sensitivity up to 87.3%, and achieve a specificity of 88.5%.
      CONCLUSION: The combined detection of miRNA-29b and AFP aids the diagnosis of PHC
      and the prediction of its prognosis.

PMID- 23863671
TI  - [Abnormal expression of insulin-like growth factor-II and intervening of its mRNA
      transcription in the promotion of HepG2 cell apoptosis].
AB  - OBJECTIVE: To explore the expression and pathological features of insulin-like
      growth factor-II (IGF-II) in tissues and sera of hepatocellular carcinoma (HCC)
      patients and the siRNA-mediated inhibition of IGF-II mRNA transcription in human
      HepG2 cells. METHODS: From December 2009 to August 2010, the self-control HCC,
      paracancerous and distal cancerous tissues were collected to analyze the
      expression of IGF-II. The serum levels of IGF-II expression were detected for
      pathological features. IGF-II expression in HepG2 cells was intervened by siRNA.
      IGF-II mRNA or IGF-II level and analyzed by reverse transcription-polymerase
      chain reaction (RT-PCR), real-time PCR or enzyme-linked immunosorbent assay
      (ELISA). And the ratio of cell apoptosis was analyzed by EdU/Hoechst33342.
      RESULTS: The levels of IGF-II expression in HCC tissues at mRNA (100%, 30/30) or
      protein (83.3%, 25/30) were significantly higher (P < 0.01) than those in para
      cancerous (46.7%, 53.3%) or distal cancerous tissues (0, 0). The serum level of
      IGF-II was significantly higher in HCC patients (3.74 +/- 0.67) ng/L than that in
      cases with benign liver diseases (1.93 +/- 0.17) ng/L and controls (1.14 +/-
      0.14) ng/L (P < 0.001). The expression of IGF-II in the HCC group was associated
      with HBV infection (t = 5.390, P < 0.001). After siRNA transfection, the
      expression of IGF-II decreased significantly in HepG2 cells at mRNA or protein
      levels. The down-regulated expression of IGF-II was dependent on the dose and
      time of IGF-II siRNA. And the apoptotic index of HepG2 cells and the sensitivity
      to adriamycin both increased. CONCLUSION: The expression of IGF-II is closely
      associated with the progression of HCC. And the intervening of its transcription
      may promote apoptosis and sensitize to adriamycin.

PMID- 23863672
TI  - [Incidence and related risk factors of diabetic ketoacidosis in Guangdong type 1
      diabetics].
AB  - OBJECTIVE: To determine the incidence and the predictors of diabetes ketoacidosis
      (DKA) in Chinese type 1 diabetics so as to lay a foundation for better prevention
      and treatment. METHODS: For this cross-sectional study, a total of 611 patients
      with established type 1 diabetes between August 6, 2010 and March 31, 2012 were
      recruited from 16 hospitals in Guangdong Province. And 491 of them were over 18
      years old. A data entry form was used to collect the patient information on
      demographics, medical history, acute/chronic complications, smoking/drinking
      status, diet, exercise, physical examination and treatment, etc. Hemoglobin A1c
      (HbA1c) and stimulated C peptide levels were centrally measured. The incidence
      rate of diabetic ketoacidosis (DKA) was calculated at events per 100 patient
      years. To determine the predictors of DKA, Poisson's regression model was used
      for analysis. And backward stepwise logistic regression analysis was performed to
      identify the predictors of DKA recurrence. The protocol and informed consent form
      were approved by Ethics Committee of Third Affiliated Hospital, Sun Yat-sen
      University. Written informed consent was obtained from patients (age > 18 years)
      or their legal guardians (age < 18 years). RESULTS: Among them, 53.7% were
      females. The mean age was 27.8 years (range: 19.5 - 37.3). The age of onset was
      22.7 (14.0 - 31.4) years old and disease duration 4.3 (1.7 - 7.9) years.
      Overweight and obese patients accounted for 10.8% and 1.0% respectively. Among
      them, the self-monitoring frequency of blood glucose was 0.4 (0.1 - 1.4) times
      per day. Overall, 26.4% patients reached the target of age-specific HbA1c values.
      The overall incidence of DKA was 26.4 per 100 patient-years. Significant
      predictors of DKA in the Poisson regression model were females (RR = 2.12),
      medical insurance claiming percentage below 50% (RR = 1.84), uncontrolled diet
      (never controlled diet vs. usually controlled diet, RR = 1.76), smoking (RR =
      2.18) as well as worse glycemic control (HbA1c per 1.0% increment, RR = 1.15).
      Totally, 34.4% of DKA episodes occurred in 3.8% of type 1 diabetics with
      recurrent events (no less than 2 episodes). The recurrence of DKA was associated
      with females (RR = 10.56), smoking (RR = 6.99), worse beta cell function
      (stimulated C peptide per 100 pmol/L decrement, RR = 4.88) and worse glycemic
      control (HbA1c per 1.0% increment, RR = 1.16). CONCLUSION: There is a high
      incidence of DKA in Chinese type 1 diabetics. And it is recurrent in high-risk
      patients. Comprehensive management should be offered to control modifiable risk
      factors in these patients.

PMID- 23863673
TI  - [Hematologic adverse effects in patients with renal cell carcinoma treated with
      sunitinib].
AB  - OBJECTIVE: To explore the hematologic adverse effects in patients with renal cell
      carcinoma treated with sunitinib. METHODS: A total of 136 patients with advanced
      renal cell carcinoma were treated with sunitinib at our hospital from 2008 to
      2011. There were 91 males and 45 females with an average age of 55.5 years. They
      received sunitinib in repeated 6-week cycles consisting of 4 weeks of sunitinib
      50 mg per day followed by 2 weeks of treatment (schedule 4/2). The hematologic
      toxicities, collected at baseline and 14, 28, 42 (after a 2-week rest period)
      days, were graded according to the National Cancer Institute common terminology
      criteria for adverse events version 3.0. The paired Wilcoxon test was used to
      evaluate the kinetics of hematologic adverse effects at days 14, 28, and 42 post
      treatment. RESULTS: The hematologic toxicities included leukopenia (n = 91,
      66.9%), neutropenia (n = 95, 69.8%), lymphopenia (n = 58, 46.2%), thrombopenia (n
      = 89, 65.4%) and hypohemoglobinemia (n = 48, 35.3%). Among them, 31 cases (22.8%)
      had the high-grade (including grades 3 and 4) toxicity of thrombopenia. There
      were depressions in hematopoietic cell populations including leukocytes,
      neutrophils, and platelets at days 14, 28 and 42 versus the baseline level (all P
      < 0.05). The median hemoglobin level transiently increased at days 14 and 28
      (both P < 0.01) and returned to the level of baseline at days 42 (P = 0.754).
      CONCLUSIONS: The incidence of hematologic adverse effects of sunitinib slightly
      varies with what have been observed in previous studies. And the incidence of
      high-grade toxicity of thrombocytopenia is higher than that reported in studies
      conducted in the US and Europe.

PMID- 23863674
TI  - [Prognostic associations of preoperative plasma levels of fibrinogen and D-dimer
      after curative resection in patients with colorectal cancer].
AB  - OBJECTIVE: To explore the associations of preoperative plasma levels of
      fibrinogen and D-dimer with clinicopathologic parameters and overall survival in
      colorectal cancer patients after curative resection. METHODS: From January 2002
      to December 2003, a total of 341 colorectal cancer patients underwent curative
      resection. And their relevant clinical data were reviewed. The median age was 58
      years (range: 23 - 90 years) and the median follow-up period was 64 months
      (range: 5 - 89 months). The preoperative plasma levels of fibrinogen and D-dimer
      were examined, the correlation of clinicopathologic findings and overall survival
      was analyzed. A Log-rank test was used for univariate analysis and a Cox
      regression model for multivariate analysis. RESULTS: The preoperative plasma
      levels of fibrinogen and D-dimer were (3.7 +/- 0.7) g/L and (0.49 +/- 0.18) mg/L
      respectively. Elevated plasma levels of fibrinogen were associated with advanced
      tumor stage (P = 0.008), venous invasion (P = 0.006), postoperative distant
      metastases (P < 0.01) and lymph node involvement (P = 0.001), but not with
      histologic grade (P = 0.232), and invasion depth (P = 0.253). The overall
      survival is 64.5% (220/341). Elevated plasma levels of D-dimer were associated
      with advanced tumor stage (P = 0.013), invasion depth (P = 0.007) and lymph node
      involvement (P = 0.001), but not with histologic grade (P = 0.082), venous
      invasion (P = 0.746) or postoperative distant metastases (P = 0.131).
      Multivariate analysis showed that preoperative plasma levels of fibrinogen (P =
      0.029), histologic grade (P = 0.001), and lymph node involvement (P = 0.001) were
      independent prognostic factors. CONCLUSIONS: High preoperative plasma levels of
      fibrinogen and D-dimer are associated with clinicopathologic parameters. And a
      high preoperative plasma level of fibrinogen is associated with distant
      metastases and poor prognosis after curative resection in colorectal cancer
      patients.

PMID- 23863675
TI  - [Association between interleukin-1B polymorphisms and chronic obstructive
      pulmonary disease: a meta-analysis].
AB  - OBJECTIVE: To explore the association between the -511C/T, -31T/C and +3954C/T
      polymorphisms of interleukin-1B (IL-1B) gene and chronic obstructive pulmonary
      disease (COPD) using the method of meta-analysis. METHODS: Comprehensive searches
      were performed of PubMed, Embase, Ovid, Wanfang and Chinese journal full-text
      database to retrieve the related case-control studies. The pooled odds ratios
      were performed respectively for allele comparison, additive genetic model,
      dominant genetic model and recessive genetic model and subgroup analysis was also
      performed by ethnicity. RESULTS: Seven case-control studies were included for
      meta-analysis. Pooled analysis showed that neither -511C/T, -31T/C nor +3954 C/T
      polymorphisms increased the susceptibility to COPD. In the subgroup analysis by
      ethnicity, significant risks were found in the Caucasian population for -511C/T T
      allele (OR = 1.76, 95%CI 1.22 - 2.54, P = 0.002), but not in the Asian population
      (OR = 0.94, 95%CI 0.64 - 1.38, P = 0.736). Significant risks were also found in
      the Caucasian population for -31T/C C allele (OR = 0.62, 95%CI 0.40 - 0.97, P =
      0.035), but not in the Asian population (OR = 1.06, 95%CI 0.89 - 1.26, P =
      0.533). CONCLUSIONS: IL-1B polymorphisms may play a role in the susceptibility of
      COPD in an ethnicity-specific manner. In the Caucasian population, the risk of
      COPD was associated positively with the IL-1B -511C/T T allele and negatively
      with the IL-1B -31T/C C allele.

PMID- 23863676
TI  - [Clopidogrel resistance of patients with coronary artery disease and its
      correlation with platelet count and mean platelet volume].
AB  - OBJECTIVE: To explore the association between clopidogrel resistance (CR) as
      assessed by whole blood electrical impedance aggregometry (EIA) and platelet
      parameters. METHODS: The prospective study comprised 152 patients with coronary
      artery disease (CAD) on the therapy of clopidogrel. EIA employed adenosine
      diphosphate (ADP) as an inductor to measure platelet aggregation. CR was defined
      by spontaneous aggregation (electrical impedance >= 10 Omega). The subjects were
      divided into 2 groups of CR and clopidogrel sensitive (CS). Platelet parameters
      were measured by routine blood test. And their clinical data and outcomes were
      analyzed. RESULTS: The prevalence of CR was 10.5% (n = 16). The ratio of patients
      with diabetes in CR group was higher than that in CS group (7/16 vs 29/136, P =
      0.046). Platelet counts and mean platelet volume (MPV) were also higher in CR
      group than those in CS group ((241 +/- 58) *10(9)/L vs (185 +/- 56)*10(9)/L, (8.0
      +/- 0.8) fl vs (7.4 +/- 0.9) fl, both P < 0.05). Logistic regression indicated
      each 10*10(9)/L increase in platelet and each 1 fl increase in MVP were
      associated with 0.376 and 1.015 folds increase in CR onset respectively (OR =
      1.376, 95%CI 1.097 - 1.725, P = 0.006;OR = 2.015, 95%CI 1.148 - 3.537, P =
      0.015). The patients with CR had more cardiovascular events during an average
      follow-up of 53 months (6/16 vs 23/136, P = 0.047). CONCLUSIONS: CAD patients
      with CR had higher incidence of cardiovascular events. Increased platelet counts
      and MPV levels are independent predictors for CR in CAD patients.

PMID- 23863677
TI  - [Clinical study of repairing donor site of thickness from cicatricial skin with
      auto-scalp grafting].
AB  - OBJECTIVE: To study the effects of using auto-scalp for repairing donor site of
      thickness from cicatricial skin with auto-scalp grafting. METHODS: A total of 13
      cases with donor site of thickness from cicatricial skin from January 2011 to
      December 2011 were analyzed. Wounds of donor site from cicatricial skin were
      grafted with auto-scalp and scalp were fixation was applied with negative
      pressure. The survival rate of auto-scalp graft was observed at Day 7 post
      operation. At Month 12, hyperplastic scars at these donor sites of cicatricial
      skin were assessed through Vancouver Scar Assessment Table, scar itch assessment
      and scar proliferation rate. Wounds in the other thirteen cases with donor site
      of thickness from cicatricial skin from January 2010 to December 2010 were
      covered with vaseline gauze as control. RESULTS: No significant difference
      existed in the gender and age of the two groups patients (P > 0.05). The auto
      scalp graft all survived. And the average healing time of donor-site wound in
      cicatricial skin in grafting group (7 days) was significantly decreased than that
      of control group (a mean of 20 days) (P < 0.01). After followed up for twelve
      months, the scar formation assessment value (1.5 +/- 0.5), scar itch assessment
      (1.2 +/- 0.4) and scar proliferation rate (14.6% +/- 7.6%) in grafting group were
      significantly less than those of control group (6.7 +/- 1.1, 2.0 +/- 0.7, 55.8%
      +/- 12.2%, all P < 0.01). CONCLUSION: Auto-scalp grafting may greatly shorten the
      healing procedure and ameliorate the quality of donor-site of thickness from
      cicatricial skin.

PMID- 23863678
TI  - [Clinical observation of accelerated partial-breast intensity-modulated
      radiotherapy in patients with early-stage breast cancer after breast-conserving
      surgery].
AB  - OBJECTIVE: To explore the clinical feasibility of accelerated partial breast
      irradiation (APBI) by intensity-modulated radiotherapy (IMRT). METHODS: Twenty
      six patients with T1N0M0 breast cancer were enrolled into a prospective
      accelerated partial-breast IMRT protocol between January 2008 and January 2010.
      Inverse planning of IMRT was employed at a prescribed dose of 34 Gy/10 f/5 d.
      Acute radiation skin responses and clinical effects were observed. RESULTS: All
      of them completed radiation. During the radiation, Grade 1 of acute radiation
      skin reaction (mild hyperpigmentation) was seen in 8 patients and there was not >
      grade 2 of skin reaction. At Month 1 post-radiation, Grade 1 of acute radiation
      skin reaction (mild hyperpigmentation) was seen in all patients and there was not
      > grade 2 of skin reaction. At Month 3 post-radiation, all instances of acute
      radiation skin reactions recovered. The median follow-up period was 51 months
      (range: 35 - 59). The follow-up period of 23 patients were over 3 years. No local
      recurrences developed. The 3-year disease-free survival was 100%. Cosmesis was
      good or excellent in all cases at Year 2. CONCLUSION: External beam-partial
      breast irradiation delivered by IMRT is feasible for selected Chinese early-stage
      breast cancer patients after breast-conserving surgery. The cosmetic effect,
      local control rate and long-term survival rate are satisfactory. And acute
      radiation toxicity is quite low.

PMID- 23863679
TI  - [Analyses of carotid intima-media thickness and quantitative arterial stiffness
      in type 2 diabetes mellitus patients with follow-ups].
AB  - OBJECTIVE: To explore the change pattern of carotid stiffness and its
      relationship between intima-media thickness (IMT) in type 2 diabetes mellitus
      (T2DM). METHODS: Quantitative intima-media thickness (QIMT) and quantitative
      arterial stiffness (QAS) were performed on bilateral carotids of 72 T2DM patients
      in May 2009 and February 2011 separately. IMT, compliance coefficient (CC),
      alpha, beta and pulse wave velocity (PWV) were measured. Their relationship was
      analyzed. RESULTS: Comparing with ultrasound result in 2009, CC of bilateral
      carotids increased (left 0.9 +/- 0.4 vs 1.1 +/- 0.4, P = 0.016; right 1.1 +/- 0.5
      vs 1.2 +/- 0.5, P = 0.012). IMT increased while alpha, beta and PWV decreased (P
      > 0.05) in 2011. No correlation existed between carotid IMT and QAS parameters.
      CONCLUSION: The glycemic, lipid and blood pressure controls decrease the carotid
      stiffness of patients with T2DM. Carotid IMT and stiffness.

PMID- 23863680
TI  - [Reactive oxygen species mediate the injury and deficient hematopoietic
      supportive capacity of umbilical cord derived mesenchymal stem cells induced by
      iron overload].
AB  - OBJECTIVE: To explore the effects of iron overload on umbilical cord derived
      mesenchymal stem cells (UC-MSC) and elucidate the involvement of reactive oxygen
      species (ROS) in this process. METHODS: The iron overload model of MSC was
      established by in vitro addition of ferric ammonium citrate (FAC) into culture
      medium. Cell proliferation and apoptosis were determined by Annexin V/PI double
      staining and population doubling time (DT) respectively. Co-culture system was
      used to assess the hematopoietic support capacity of UC-MSC in different groups.
      Thereafter the ROS level was detected with fluorescent probe 2', 7'
      dichlorofluorescin diacetate (DCFH-DA). And the ROS related signaling factors of
      p-p38MAPK, p38 MAPK, P53 were measured by Western blot. RESULTS: (1) The DT of UC
      MSC in iron overload group was significantly longer than that of control ((24.43
      +/- 2.72) h vs (16.03 +/- 2.31) h, P < 0.05). But the difference was
      insignificant after two passages (P > 0.05). (2) Apoptosis in iron overload group
      was higher than that of control (12.75% +/- 0.32% vs 3.63% +/- 0.80%, P < 0.05).
      (3) The colony forming capacity of mononuclear cell (MNC) co-cultured with UC-MSC
      of iron overload group for 1/2 weeks significantly decreased. (4) The ROS level
      of UC-MSC with iron overload was higher than that of control in time and
      concentration-dependent fashions and it peaked at 400 umol/L of FAC for 12 h
      (1499 +/- 86 vs 548 +/- 97, P < 0.05). (5) The expressions of p-p38MAPK and P53
      increased in response to FAC compared with control. But such an effect was
      partially inhibited after the use of antioxidants. CONCLUSIONS: Iron overload may
      impair the proliferation, survival and hematopoiesis supportive function of UC
      MSC by enhancing the generation of ROS. And ROS stimulates the signaling pathways
      of p-p38MAPK and P53.

PMID- 23863681
TI  - [Effects of Ghrelin on hypertension and insulin resistance in fructose-fed rats].
AB  - OBJECTIVE: To explore the effects and mechanisms of Ghrelin on hypertension and
      insulin resistance in fructose-fed rats. METHODS: A total of 32 male Sprague
      Dawley (SD) rats were randomized into control (A) and fructose-fed groups (B).
      Rats in group B were fed with 10% fructose solution for 4 weeks. Then the rats in
      group A were randomized into intraperitoneal saline (group GA1) or
      intraperitoneal 50 nmol/kg Ghrelin (group GA2) and those in group B into
      intraperitoneal saline (group GB1) or intraperitoneal 50 nmol/kg Ghrelin (group
      GB2) twice daily for 6 weeks. Caudal arterial pressure was measured weekly.
      Plasma blood glucose, insulin concentration and lipid profile were measured. And
      insulin resistance (IR) was calculated by the method of homeostasis model
      assessment (HOMA). Plasma level of 15-F2t-isoprostane was measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Ghrelin caused a significant
      reduction of systolic pressure at Week 3 in group GB2 versus group GB1 (P <
      0.05). Maximal effect appeared at Week 5 ((127 +/- 5) vs (120 +/- 6) mm Hg, P <
      0.05, 1 mm Hg = 0.133 kPa), but blood pressure failed to reach normal value.
      Ghrelin also decreased plasma insulin concentration and HOMA-IR ((9.6 +/- 2.6) vs
      (13.1 +/- 3.6) uU/ml, P < 0.05;1.92 +/- 0.12 vs 2.78 +/- 0.14, P < 0.01). Plasma
      level of 15-F2t-isoprostane was lower in group GB2 than that in group GB1 ((75 +/
      11) vs (102 +/- 14) pg/ml, P < 0.01). CONCLUSION: Ghrelin may lower blood
      pressure, ameliorate insulin resistance and improve insulin sensitivity through
      inhibiting oxidative stress in fructose-induced rats.

PMID- 23863682
TI  - [Voltage dependent anion channel 2 involved mitochondrial apoptosis and its
      possible regulatory signal pathway in hearts of rats with severe scalds].
AB  - OBJECTIVE: To explore the role of voltage dependent anion channel 2 (VDAC2)
      involved mitochondrial apoptosis in heart injury of rats with severe scald injury
      and elucidate its possible regulatory signal pathway. METHODS: A total of 60
      Wistar rats were divided into sham scald group (n = 30) and scald group (n = 30)
      according to a random digital table. Blood and heart tissue samples were
      harvested at Day 1, 7, 14 post scalding. Myocardial injury was assessed with
      cardiac troponin I (cTnI) by enzyme-linked immunosorbent assay (ELISA).
      Mitochondrial apoptosis activation was evaluated by the expressions of Bax/Bcl-2
      ratio, cytoplasmic cytochrome C and VDAC2. And the levels of phosphatidylinositol
      3-kinase, p-Glycogen Synthase Kinase-3beta and hexokinase 2 protein were
      determined by Western blot. RESULTS: The serum levels of cTnI were significantly
      higher in scald group than those in sham scald group at Day 1, 7, 14 ((1.41 +/-
      0.25) vs (0.53 +/- 0.23) ug/L, (1.93 +/- 0.53) vs (0.43 +/- 0.23) ug/L, (1.62 +/-
      0.34) vs (0.41 +/- 0.22) ug/L respectively, all P < 0.05). Compared with sham
      scald group, Bax/Bcl-2 ratio increased significantly in scald group at Day 1, 7
      day post-scalding (3.360 +/- 0.173 vs 0.623 +/- 0.044, 2.736 +/- 0.341 vs 0.698
      +/- 0.064, 1.290 +/- 0.234 vs 0.718 +/- 0.063 respectively, all P < 0.05), VDAC2
      protein level in scald group decreased significantly at Day 1, 7, 14 (0.070 +/-
      0.009 vs 0.328 +/- 0.026, 0.007 +/- 0.002 vs 0.291 +/- 0.025, 0.009 +/- 0.004 vs
      0.302 +/- 0.037 respectively, all P < 0.05), the cytoplasmic levels of cytochrome
      increased significantly in scald group at Day 1, 7, 14 (0.418 +/- 0.030 vs 0.022
      +/- 0.007, 1.685 +/- 0.169 vs 0.030 +/- 0.011, 0.300 +/- 0.037 vs 0.098 +/- 0.014
      respectively, all P < 0.05), the expression of PI3K was significantly lower in
      scald group at Day 14 post-scalding (0.083 +/- 0.015 vs 0.328 +/- 0.011, P <
      0.05), the expressions of p-GSK3beta all reduced significantly at Day 1, 7, 14
      (0.098 +/- 0.014 vs 0.446 +/- 0.031, 0.064 +/- 0.002 vs 0.476 +/- 0.054, 0.074 +/
      0.010 vs 0.442 +/- 0.041, respectively, all P < 0.05) and the expressions of HK2
      were lower at Day 7, 14 post-scalding (0.390 +/- 0.027 vs 0.611 +/- 0.070, 0.267
      +/- 0.018 vs 0.490 +/- 0.042, respectively, all P < 0.05). CONCLUSIONS: VDAC2
      involved mitochondrial apoptosis is activated in myocardium after severe scalds.
      And it may be regulated by the pathway of PI3K-GSK-HK2.

PMID- 23863683
TI  - [Effects of lipoxinA4 on endoplasmic reticulum stress during myocardial ischemia
      reperfusion injury in rats].
AB  - OBJECTIVE: To explore the protective effect of lipoxin (LX)A4 during myocardial
      ischemia reperfusion injury (MIRI) and discuss the molecular mechanism of
      excessive endoplasmic reticulum stress (ERS) in rats. METHODS: Seventy-two male
      SD rats were divided into 6 groups, according to random number table, 12 in each
      group: sham operation group (group sham)1, 2: injected with normal saline (NS) 2
      ml/kg before and after coronary artery threading. MIRI group (group I/R)1, 2:
      injected with NS 2 ml/kg before and after MIRI. Group LX1, LX2: injected with
      LXA4 100 ug/kg in 2 ml/kg NS before and after MIRI treatment. After the rat MIRI
      model was established, the serum concentrations of troponin I (cTnI) were
      measured in each group before open-chest operation (T1) and at the end of the
      experiment (T2). Besides, expressions of GRP-78, caspase-12 protein and mRNA were
      test. At the same time, myocardial cell apoptosis, the myeloperoxidase (MPO),
      superoxide dismutase (SOD) activation and malondialdehyde (MDA) content were
      detected while the HE and ultrastructural changes of cardiac muscle were
      observed. RESULTS: The expression levels of GRP-78, caspase-12 protein and mRNA,
      apoptotic index, serum cTnI concentrations (T2) and MPO, SOD activation, MDA
      content were all significantly higher in groups I/R and LX than those in group
      sham 1 and sham 2 (all P < 0.05). The expression levels of GRP-78, caspase-12
      protein in group LX1 (compared with group I/R1) and in group LX2 (compared with
      group I/R2) were all significantly lower (all P < 0.05). Besides, the expression
      of GRP-78, caspase-12 mRNA in group LX1 were significantly less than those in
      group I/R1 ((0.86 +/- 0.06)*10(5) vs (1.95 +/- 0.65)*10(5), (12.35 +/-
      4.15)*10(5) vs (23.76 +/- 6.57) *10(5), both P < 0.05), so were those in groups
      LX2 and I/R2 ((0.64 +/- 0.05)*10(5) vs (2.36 +/- 0.57)*10(5), (7.04 +/-
      0.81)*10(5) vs (26.49 +/- 6.82)*10(5), both P < 0.05). The apoptotic index, the
      serum concentrations of cTnI (T2), MPO activation and MDA content were all
      significantly lower in group LX1 than those in group I/R1 (34.6% +/- 5.7% vs
      52.5% +/- 6.4%, (293 +/- 22) vs (581 +/- 44) ng/L, (176 +/- 47) vs (331 +/- 94)
      U/g tissue, (1549 +/- 238) vs (2403 +/- 439) nmol/g protein, both P < 0.05), so
      were those in groups LX2 and I/R2(26.5% +/- 4.6% vs 54.8% +/- 6.3%, (207 +/- 29)
      vs (593 +/- 61) ng/L, (99 +/- 24) vs (329 +/- 92) U/g tissue, (1055 +/- 237) vs
      (2422 +/- 518) nmol/g protein, all P < 0.05). In addition, the activity of SOD in
      groups LX1 and LX2 were both significantly higher respectively than those in
      groups I/R1 and I/R2 (both P < 0.05). Moreover, compared with groups I/R1 and
      I/R2, the neutrophils infiltration were significantly less than those in groups
      LX1 and LX2 respectively, and the ultrastructure damage were also much milder.
      CONCLUSIONS: Before and after MIRI, application of LXA4 may significantly inhibit
      neutrophil infiltration and attenuate myocardial oxidative injury. LXA4 play its
      role in myocardial protection via down-regulating the expression of GRP-78,
      caspase-12 and the inhibition of excessive ERS.

PMID- 23863684
TI  - [Effects of intraperitoneal injection of marrow mesenchymal stem cells on
      intestinal barrier in acute pancreatitis].
AB  - OBJECTIVE: To explore the effects of intraperitoneal injection of mesenchymal
      stem cells (MSC) on intestinal barrier in serve acute pancreatitis (SAP) rats.
      METHODS: MSC were harvested and cultured from femurs of one male SD rat. And 30
      female SD rats were divided into 3 groups: control group (n = 6), SAP group (n =
      12) and MSC transplantation group (n = 12). SAP was induced by intraperitoneal
      injection of L-arginine (2 g/kg) twice in SAP and MSC groups. In MSC group, the
      third-generation MSC (5*10(6)) were injected intraperitoneally once daily for 3
      days. All rats were sacrificed after 72 h. The histomorphologic alternations of
      small intestine were measured to evaluate the therapeutic effect of MSC
      transplantation. Reverse transcription (RT)-PCR were used to identify the
      expression of TNF-alpha mRNA and IL-1beta mRNA in small intestine and pancreas.
      Small intestine and pancreatic samples were examined for the engraftment of donor
      derived MSC by Y chromosome in situ hybridization analysis. RESULTS: Compared
      with SAP group, histomorphologic alternations of small intestine significantly
      lower in MSC group (4.17 +/- 0.28 vs 3.00 +/- 0.33, P < 0.05). The relative
      expression quantity of TNF-alpha mRNA and IL-1beta mRNA in pancreas were both
      significant higher in SAP and MSC groups than those in control group (3.10 +/-
      0.73 and 1.92 +/- 0.37 vs 0.51 +/- 0.24, 4.60 +/- 0.59 and 2.43 +/- 0.39 vs 1.15
      +/- 0.18, all P < 0.05). Compared with SAP group, the expression quantity of TNF
      alpha mRNA and IL-1beta mRNA in pancreas significantly lower in MSC group (both P
      < 0.05). The relative expression quantity of TNF-alpha mRNA and IL-1beta mRNA in
      small intestine were both significant higher in SAP and MSC groups than those in
      control group (2.73 +/- 0.91 and 1.55 +/- 0.48 vs 0.62 +/- 0.20, 5.20 +/- 0.94
      and 2.10 +/- 0.34 vs 0.99 +/- 0.10, all P < 0.05). The expressions of TNF-alpha
      mRNA and IL-1beta mRNA in MSC group were lower than those in SAP group (both P <
      0.05). Sry gene was not detected in pancreatic and intestinal tissue of MSC
      treated rats. CONCLUSIONS: Syngraft MSC exert protective effects on pancreas and
      small intestine injury. And their beneficial effects are primarily mediated via
      indirect actions but not by their differentiation into target cells.

PMID- 23863685
TI  - High-risk ECG patterns in ACS--need for guideline revision.
AB  - The current guidelines advocate distinct approaches (urgent reperfusion therapy)
      to patients with suspected acute coronary syndromes (ACS) presenting with ST
      elevation (STE) versus patients without STE on their electrocardiogram (ECG).
      This is based on the paradigm that STE represents ongoing transmural ischemia due
      to an acute occlusion of an epicardial coronary artery whereas the significance
      of other ECG findings is more contentious. The role of urgent coronary
      angiography in patients without STE is less clear and initial stabilization with
      conservative treatment is recommended. However, in some cases the distinction
      between STEMI and non-STE-ACS is difficult. Acute occlusion of a coronary artery
      may cause less than the current recommended threshold STE. On the other hand,
      many patients may have STE secondary to nonischemic etiology. In many patients
      with non-STE-ACS the coronary artery is not completely occluded at the time of
      presentation and there are rapid fluctuations in the severity of ischemia and
      hence, dynamic changes are observed in the ECG. Several ECG patterns associated
      with particular coronary anatomy and high-risk prognosis have been identified.
      Patients with ACS presenting with these high-risk patterns should probably be
      referred for coronary angiography with the possibility of urgent intervention
      with the goal of prevention of ischemic complications, rather than for immediate
      myocardial salvage, as in classic STEMI. 

PMID- 23863686
TI  - Saliency and saccade encoding in the frontal eye field during natural scene
      search.
AB  - The frontal eye field (FEF) plays a central role in saccade selection and
      execution. Using artificial stimuli, many studies have shown that the activity of
      neurons in the FEF is affected by both visually salient stimuli in a neuron's
      receptive field and upcoming saccades in a certain direction. However, the extent
      to which visual and motor information is represented in the FEF in the context of
      the cluttered natural scenes we encounter during everyday life has not been
      explored. Here, we model the activities of neurons in the FEF, recorded while
      monkeys were searching natural scenes, using both visual and saccade information.
      We compare the contribution of bottom-up visual saliency (based on low-level
      features such as brightness, orientation, and color) and saccade direction. We
      find that, while saliency is correlated with the activities of some neurons, this
      relationship is ultimately driven by activities related to movement. Although
      bottom-up visual saliency contributes to the choice of saccade targets, it does
      not appear that FEF neurons actively encode the kind of saliency posited by
      popular saliency map theories. Instead, our results emphasize the FEF's role in
      the stages of saccade planning directly related to movement generation. 

PMID- 23863687
TI  - Selective disruption of sociocognitive structural brain networks in autism and
      alexithymia.
AB  - Autism spectrum conditions (ASC) are neurodevelopmental disorders characterized
      by abnormal social cognition. A core feature of ASC is disrupted Theory of Mind
      (ToM), our ability to take the mental perspective of others. ASC is also
      associated with alexithymia, a trait characterized by altered emotional
      interoception and empathy. Here, we applied structural MRI covariance analysis to
      assess whether ASC and alexithymia differentially affect structural brain
      networks associated with sociocognitive and socioaffective functions. Based on
      previous functional MRI findings, we expected disrupted ToM networks (centered on
      dorsomedial prefontal cortex [dmPFC], and temporo-parietal junction [TPJ]) in
      ASC, while alexithymia would affect networks centered on fronto-insular cortex
      (FI), regions associated with interoception of emotion and empathy. Relative to
      controls, ASC indeed showed reduced covariance in networks centered on dmPFC and
      TPJ, but not within FI networks. Irrespective of ASC, covariance was negatively
      modulated by alexithymia in networks extending from FI to posterior regions.
      Network findings were complemented by self-reports, indicating decreased
      perspective taking but normal empathic concern in ASC. Our results show divergent
      effects of ASC and alexithymia on inter-regional structural networks, suggesting
      that networks mediating socioaffective processes may be separable from networks
      mediating sociocognitive processing. 

PMID- 23863688
TI  - Lobectomy in follicular thyroid neoplasms' treatment.
AB  - BACKGROUND: The purpose of this study is to evaluate the suitability of lobectomy
      with isthmectomy (LwI) in treatment of Follicular Thyroid Neoplasms (FTN),
      considering malignancy incidence and postoperative complications. METHODS: 192
      patients (165 females; 27 males) who underwent LwI for FTN from 01/2005 to
      12/2007 were retrospectively evaluated: clinical and pathological features,
      surgical complications and five year outcome. Inclusion criteria were cytological
      Bethesda category III and IV or histological follicular adenoma/carcinoma or
      follicular variant of papillary carcinoma). Metastatic disease or previous
      thyroidal surgery patients were excluded. RESULTS: Mean age was 48.68 +/- 14.93
      yrs. Overall malignancy occurred in 88 patients (45.83%) and 80 (41.67%)
      underwent thyroidectomy completion (TC), mainly by index lesion's malignancy.
      Forty-one (21.35%) in LwI and 31 (38.75%) in TC specimens had associated
      malignancy, mainly papillary microcarcinomas. High preoperative Thyroid
      Stimulating Hormone (TSH), histological multinodularity and, in cytology category
      IV, younger age, were significantly associated to malignancy. Permanent recurrent
      laryngeal nerve lesion occurred in 0.58% in Lwl and 1.52% in TC, and temporary
      dysphonia occurred in 9.25% and 6.06% (LwI and TC respectively). No LwI patients
      presented hypoparathyroidism whereas 3.03% in TC had temporary symptoms. In LwI,
      36.70% developed hypothyroidism. Higher preoperative TSH was associated with
      hypothyroidism development. CONCLUSIONS: LwI was inappropriate in 40.10% patients
      with malignancy who required TC and 23.12% had no functional benefit because post
      LwI hypothyroidism. Nodular relapse was reported in at least 23/113 LwI patients
      (20.35%). We propose total thyroidectomy for patients with FTN preoperative TSH
      higher than 2.16 mU/L and, in Bethesda category IV, less than 39.5yrs.

PMID- 23863689
TI  - Clinical advances in molecular biomarkers for cancer diagnosis and therapy.
AB  - Cancer diagnosis is currently undergoing a paradigm shift with the incorporation
      of molecular biomarkers as part of routine diagnostic panel. The molecular
      alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and
      proteins. The miRNAs are recently discovered small non-coding endogenous single
      stranded RNAs that critically regulates the development, invasion and metastasis
      of cancers. They are altered in cancers and have the potential to serve as
      diagnostic markers for cancer. Moreover, deregulating their activity offers novel
      cancer therapeutic approaches. The availability of high throughput techniques for
      the identification of altered cellular molecules allowed their use in cancer
      diagnosis. Their application to a variety of body specimens from blood to tissues
      has been helpful for appreciating their use in the clinical context. The
      development of innovative antibodies for immunohistochemical detection of
      proteins also assists in diagnosis and risk stratification. Overall, the novel
      cancer diagnostic tools have extended their application as prognostic risk
      factors and can be used as targets for personalized medicine. 

PMID- 23863690
TI  - Extracellular microRNAs in urologic malignancies: chances and challenges.
AB  - Small noncoding RNAs that are 19-23 nucleotides long, known as microRNAs
      (miRNAs), are involved in almost all biological mechanisms during carcinogenesis.
      Recent studies show that miRNAs released from live cells are detectable in body
      fluids and may be taken up by other cells to confer cell-cell communication.
      These released miRNAs (here referred to as extracellular miRNAs) are often
      protected by RNA-binding proteins or embedded inside circulating microvesicles.
      Due to their relative stability, extracellular miRNAs are believed to be
      promising candidates as biomarkers for diagnosis and prognosis of disease, or
      even as therapeutic agents for targeted treatment. In this review, we first
      describe biogenesis and characteristics of these miRNAs. We then summarize recent
      publications involving extracellular miRNA profiling studies in three
      representative urologic cancers, including: prostate cancer, bladder cancer, and
      renal cell carcinoma. We focus on the diagnostic, prognostic, and therapeutic
      potential of these miRNAs in biological fluids, such as serum, plasma, and urine.
      Finally, we discuss advantages and challenges of these miRNAs in clinical
      applications. 

PMID- 23863693
TI  - Genetic diversity of the critically endangered Thuja sutchuenensis revealed by
      ISSR markers and the implications for conservation.
AB  - Thuja sutchuenensis Franch. is a critically endangered plant endemic to the North
      East Chongqing, China. Genetic variation was studied to assess the distribution
      of genetic diversity within and among seven populations from the single remnant
      locations, using inter-simple sequence repeat (ISSR) markers. A total of 15
      primers generated 310 well defined bands, with an average of 20.7 bands per
      primer. The seven populations revealed a relatively high level of genetic
      diversity in the species. The percentage of polymorphic bands, Nei's gene
      diversity and Shannon's information index at the population and species level
      were 76.1%, 0.155, 0.252 and 100%, 0.165, 0.295, respectively. A low level of
      genetic differentiation among populations (G(ST) = 0.102), in line with the
      results of Analyses of Molecular Variance (AMOVA), and a high level of gene flow
      (N(m) = 4.407) were observed. Both the Unweighted Pair Group Method with
      Arithmatic Mean (UPGMA) cluster analysis and Principal Coordinates Analysis
      (PCoA) supported the grouping of all seven populations into two groups. In
      addition, Mantel test revealed no significant correlation between genetic and
      geographical distances (r = 0.329, p = 0.100). The low genetic differentiation
      among populations implies that the conservation efforts should aim to preserve
      all the extant populations of this endangered species.

PMID- 23863691
TI  - Molecularly targeted agents as radiosensitizers in cancer therapy--focus on
      prostate cancer.
AB  - As our understanding of the molecular pathways driving tumorigenesis improves and
      more druggable targets are identified, we have witnessed a concomitant increase
      in the development and production of novel molecularly targeted agents.
      Radiotherapy is commonly used in the treatment of various malignancies with a
      prominent role in the care of prostate cancer patients, and efforts to improve
      the therapeutic ratio of radiation by technologic and pharmacologic means have
      led to important advances in cancer care. One promising approach is to combine
      molecularly targeted systemic agents with radiotherapy to improve tumor response
      rates and likelihood of durable control. This review first explores the
      limitations of preclinical studies as well as barriers to successful
      implementation of clinical trials with radiosensitizers. Special considerations
      related to and recommendations for the design of preclinical studies and clinical
      trials involving molecularly targeted agents combined with radiotherapy are
      provided. We then apply these concepts by reviewing a representative set of
      targeted therapies that show promise as radiosensitizers in the treatment of
      prostate cancer. 

PMID- 23863695
TI  - Pharmacological profile of 2-bromoterguride at human dopamine D2, porcine
      serotonin 5-hydroxytryptamine 2A, and alpha2C-adrenergic receptors, and its
      antipsychotic-like effects in rats.
AB  - Dopaminergic, serotonergic, and adrenergic receptors are targets for therapeutic
      actions in schizophrenia. Dopamine D2 receptor partial agonists such as
      aripiprazole represent a treatment option for patients with this severe disorder.
      The ineffectiveness of terguride, another D2 receptor partial agonist, in
      treating schizophrenia was recently attributed to its considerably high intrinsic
      activity at D2 receptors. In this study, we used functional assays for
      recombinant D2 receptors and native 5-hydroxytryptamine 2A (5-HT2A), alpha2C
      adrenergic, and histamine H1 receptors to compare the pharmacological properties
      of terguride and three of its halogenated derivatives (2-chloro-, 2-bromo-, 2
      iodoterguride) with those of aripiprazole. Subsequently, we studied the
      antidopaminergic effects of 2-bromoterguride using amphetamine-induced locomotion
      (AIL). Its influence on spontaneous behavior was tested in the open field.
      Extrapyramidal side effect (EPS) liability was evaluated by catalepsy test. In a
      guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding assay, 2
      chloro-, 2-bromo-, and 2-iodoterguride produced intrinsic activities at human
      D2short (hD2S) receptors that were half as high as the intrinsic activity for
      terguride; aripiprazole lacked agonist activity. 2-Bromoterguride and
      aripiprazole activated D2S receptor-mediated inhibition of cAMP accumulation to
      the same extent; intrinsic activity was half as high as that of terguride. All
      compounds tested behaved as antagonists at human D2long/Galphao (hD2L/Galphao)
      receptors. Compared with aripiprazole, terguride and its derivatives displayed
      higher affinity at porcine 5-HT2A receptors and alpha2C-adrenoceptors and lower
      affinity at H1 receptors. 2-Bromoterguride inhibited AIL and did not induce
      catalepsy in rats. Because of its in vitro and in vivo properties, 2
      bromoterguride may be a strong candidate for the treatment of schizophrenia with
      a lower risk to induce EPS. 

PMID- 23863694
TI  - Ectopic expression of BraYAB1-702, a member of YABBY gene family in Chinese
      cabbage, causes leaf curling, inhibition of development of shoot apical meristem
      and flowering stage delaying in Arabidopsis thaliana.
AB  - YABBY gene family plays an important role in the polarity development of lateral
      organs. We isolated the BraYAB1-702 gene, a member of the YABBY gene family, from
      young leaves of Chinese cabbage line 06J45. The full-length gene has a 937 bp
      CDNA sequence and contains an open reading frame (ORF) of 702 bp. The subcellular
      localization analysis showed that the expression product of the gene was
      localized in the nucleus. Ectopic expression of BraYAB1-702 in Arabidopsis
      thaliana caused leaf curling from the adaxial epidermises to abaxial epidermises;
      the partial abaxialization of the adaxial epidermises of leaves; leaf trichomes
      and stomata numbers being significantly increased; the plants being severely
      stunted; the flowering stage being remarkably delayed and inhibiting the
      development of shoot apical meristem (SAM) with the down-regulation of the
      expression of SHOOT MERISTEMLESS (STM), Brevipedicellus (BP) and KNAT2 which were
      related to the development of shoot apical meristem. These results from the
      present research help to reveal the molecular mechanism of BraYAB1-702 gene in
      the establishment of adaxial-abaxial polarity of the lateral organs in Chinese
      cabbage. 

PMID- 23863692
TI  - Posttranslational modification of the androgen receptor in prostate cancer.
AB  - The androgen receptor (AR) is important in the development of the prostate by
      regulating transcription, cellular proliferation, and apoptosis. AR undergoes
      posttranslational modifications that alter its transcription activity,
      translocation to the nucleus and stability. The posttranslational modifications
      that regulate these events are of utmost importance to understand the functional
      role of AR and its activity. The majority of these modifications occur in the
      activation function-1 (AF1) region of the AR, which contains the transcriptional
      activation unit 1 (TAU1) and 5 (TAU5). Identification of the modifications that
      occur to these regions may increase our understanding of AR activation in
      prostate cancer and the role of AR in the progression from androgen-dependent to
      castration-resistant prostate cancer (CRPC). Most of the posttranslational
      modifications identified to date have been determined using the full-length AR in
      androgen dependent cells. Further investigations into the role of
      posttranslational modifications in androgen-independent activation of full-length
      AR and constitutively active splicing variants are warranted, findings from which
      may provide new therapeutic options for CRPC. 

PMID- 23863696
TI  - Eternity and functionality - rational access to physiologically relevant cell
      lines.
AB  - In the first 50 years of cell culture, the development of new cell lines was
      mainly based on trial and error. Due to the understanding of the molecular
      networks of aging, senescence, proliferation, and adaption by mutation, the
      generation of new cell lines with physiologic properties has become more
      systematic. This endeavor has been supported by the availability of new
      technological achievements and increasing knowledge about the biology of cell
      differentiation and cell-cell communication. Here, we review some promising
      developments that are contributing toward this goal. These include molecular
      tools frequently used for the immortalization process. In addition to these
      broadly acting immortalization regimens, we focus on the developments of cell
      type-specific immortalization and on the methodologies of how to control the
      growth of newly established cell lines.

PMID- 23863697
TI  - Structural and functional insights into the Spir/formin actin nucleator complex.
AB  - The diversity of cellular actin functions is attained by the activation of actin
      nucleator complexes, which initiate the polymerization of actin monomers into a
      helical double-stranded filament at defined subcellular compartments. Next to
      actin functions at the cell membrane, including different forms of membrane
      protrusions and invaginations, actin dynamics at intracellular membranes has
      recently become a research focus. Experiments addressing the vesicle-associated
      Spir WH2 domain containing actin nucleators have provided novel mechanistic
      insights into the function of actin dynamics at intracellular membranes. Spir
      proteins are targeted by a modified FYVE zinc finger motif toward endosomal and
      vesicle membranes, where they interact and cooperate with the distinct nucleators
      of the FMN subfamily of formins in the nucleation of actin filaments. The
      function of the Spir/formin actin nucleator complex is closely related to the
      Rab11 small G protein, which is a key regulator of recycling and exocytic
      transport processes. Together with the actin motor protein and Rab11 effector
      myosin Vb, Spir/formin nucleated actin filaments mediate actin-dependent vesicle
      transport processes. Drosophila and mouse genetic studies as well as cell biology
      experiments point toward an important role of the Spir/formin complex in oocyte
      maturation and in the structure and signaling of the nervous system.

PMID- 23863698
TI  - Full-length Vpu and human CD4(372-433) in phospholipid bilayers as seen by magic
      angle spinning NMR.
AB  - HIV-1 Vpu and CD4(372-433), a peptide comprising the transmembrane and
      cytoplasmic domain of human CD4, were recombinantly expressed in Escherichia
      coli, uniformly labeled with 13C and 15N isotopes, and separately reconstituted
      into phospholipid bilayers. Highly resolved dipolar cross-polarization (CP)-based
      solid-state NMR spectra of the two transmembrane proteins were recorded under
      magic angle sample spinning. Partial assignment of 13C resonances was achieved.
      Site-specific assignments were obtained for 13 amino acid residues of CD4(372
      433) and two Vpu residues. Additional amino acid type-specific assignments were
      achieved for 10 amino acid spin systems for both CD4(372-433) and Vpu. Further,
      structural flexibility was probed with different dipolar recoupling techniques,
      and the correct insertion of the transmembrane domains into the lipid bilayers
      was confirmed by proton spin diffusion experiments.

PMID- 23863699
TI  - Short-term estimation and application of biological variation of small dense low
      density lipoproteins in healthy individuals.
AB  - BACKGROUND: A number of methods have been developed to measure small dense low
      density lipoprotein cholesterol (sd-LDL-C) to evaluate atherogenic risk in the
      population. However, to our knowledge there are no reports about the biologic
      variability of these lipoproteins. Therefore, the aim of this work was to
      estimate sd-LDL-C biological variability, and with this information establish
      quality specifications, index of individuality (II) and reference change values
      (RCV). METHODS: To estimate within- and between-subject biological variability,
      sd-LDL-C in serum was measured in 24 individuals (11 female and 13 male) for 5
      consecutive days and then, at 2 and 3 weeks. Quality specifications, II, and RCVs
      were estimated according to procedures described. RESULTS: Total within- and
      between-subject biological variability, expressed as coefficient of variation,
      was 9.1% and 20%. Meanwhile, within- and between-biological variability in female
      and men was 10.9% and 6.7%, and 22% and 17%, respectively. Desirable quality
      specification to the sd-LDL-C method was 4.6% for analytical imprecision, bias
      5.5% and total allowable error of 11.4%; the II was 0.46 and the RCV (calculated
      at 95% and 99% of significance) was 27.1% and 35.7%, for the total data.
      CONCLUSIONS: Short-term biological variability components were determined, and
      then used to estimate quality specifications, II and RCV for sd-LDL-C
      precipitation assay. To our knowledge, this is one of the first reports about sd
      LDL-C biological variability, so that this information can be used as a starting
      point to develop long-term studies of biological variability for sd-LDL-C.

PMID- 23863700
TI  - The integration of the detection of systemic sclerosis-associated antibodies in a
      routine laboratory setting: comparison of different strategies.
AB  - BACKGROUND: Detection of systemic sclerosis-associated autoantibodies (SSc-Ab) is
      mostly restricted to anti-centromere and anti-topoisomerase-I. However, anti-RNA
      polymerase-III and anti-PM/Scl are also important diagnostic markers for the
      disease supporting their incorporation in the laboratory repertoire. The aim of
      this study was to compare different testing strategies integrating the
      identification of these extra SSc-Ab in a routine testing algorithm. METHODS:
      Sera from 144 consecutive SSc-patients and 265 controls were screened for
      antinuclear antibodies (ANA) by indirect immunofluorescence (ANA IIF) and tested
      for anti-extractable nuclear antigen (ENA) using five different assays that
      differ in their ability to detect SSc-Ab [two screening enzyme immunossays (EIA)
      with antigen mixtures, one multi-parameter line-immunoassay and two EIA with
      individual antigens]. RESULTS: The application of SSc-Ab testing in cascade with
      the routine ANA/anti-ENA tests improved diagnostic performance characteristics.
      Besides the type of algorithm, also the number of antigens included in the
      screening EIA as well as the expected patient/control ratio, influenced the
      average expected costs and the number of additional SSc-Ab tests to be performed.
      In laboratories with an expected patient/control ratio of 0.002, cascade testing
      was most exploited by the use of a screening EIA that included all SSc-Ab as a
      secondary test after ANA IIF. CONCLUSIONS: Restriction of the performance of
      additional SSc-Ab assays based on the results of prior ANA/anti-ENA tests is a
      cost-effective strategy allowing optimized use of laboratory resources with
      minimal loss in diagnostic capacity.

PMID- 23863701
TI  - Mitochondrial haplotypes indicate parapatric-like phylogeographic structure in
      blue-spotted maskray (Neotrygon kuhlii) from the Coral Triangle region.
AB  - Phylogeographic structure was investigated in the blue-spotted maskray, Neotrygon
      kuhlii, focusing on the Coral Triangle region. We used as genetic marker a 519-bp
      fragment of the cytochrome c-oxidase subunit I (COI) gene, sequenced in a total
      of 147 individuals from 26 sampling locations. The parsimony network of COI
      haplotypes was split into seven distinct clades within the Coral Triangle region.
      Different clades had exclusive but contiguous geographic distributions,
      indicating parapatric-like phylogeographic structure. Strong genetic differences
      were also inferred between local populations within a clade, where reciprocal
      monophyly between geographically adjacent samples was observed on several
      instances. Nearly 25% of the total molecular variance could be ascribed to
      differences between geographic samples within a clade, whereas interclade
      variation accounted for >65% of the total variance. The strong phylogeographic
      structure observed within a clade can be explained by either sedentarity or
      female philopatry. We interpret the parapatric distribution of clades as the
      joint result of 1) expansion from refuge populations at times of low sea level,
      and 2) possible enhanced competition between individuals from different clades,
      or assortative mating, or hybrid zones, along lines of secondary contact. The
      parapatric-like structure uncovered in the present study parallels regional
      differences at nuclear marker loci, thus pointing to incipient speciation within
      Coral Triangle N. kuhlii. 

PMID- 23863702
TI  - State-specific healthy life expectancy at age 65 years--United States, 2007-2009.
AB  - Healthy life expectancy (HLE) is a population health measure that combines
      mortality data with morbidity or health status data to estimate expected years of
      life in good health for persons at a given age. HLE accounts for quantity and
      quality of life and can be used to describe and monitor the health status of
      populations. HLE estimates for countries have been used for predicting future
      health service needs, evaluating health programs, and identifying trends and
      inequalities, but to date, few studies have reported HLE at the state level for
      the United States. To determine state-level estimates, CDC used data from the
      National Vital Statistics Systems (NVSS), U.S. Census Bureau, and Behavioral Risk
      Factor Surveillance System (BRFSS) to calculate HLEs for persons aged 65 years,
      by sex and race, for each of the 50 states and the District of Columbia (DC).
      Those calculations indicate that, during 2007-2009, females had a greater HLE
      than males at age 65 years in every state and DC. HLE was greater for whites than
      for blacks in all states from which sufficient data were available and DC, except
      in Nevada and New Mexico. These results can be used as a baseline for states to
      monitor changes in the HLE of persons aged 65 years as they age and identify
      health disparities among subpopulations. 

PMID- 23863703
TI  - Salmonella enteritidis infections associated with foods purchased from mobile
      lunch trucks--Alberta, Canada, October 2010-February 2011.
AB  - During October 2010-February 2011, an outbreak of 91 Salmonella Enteritidis (SE)
      infections in Alberta, Canada, was investigated by a local public health
      department (Alberta Health Services, Calgary Zone). Index cases initially were
      linked through a common history of consumption of food purchased from mobile food
      vending vehicles (lunch trucks) operating at worksites in Alberta. Further
      investigation implicated one catering company that supplied items for the lunch
      trucks and other vendors. In 85 cases, patients reported consumption of food
      prepared by the catering company in the 7 days before illness. Six patients were
      employees of the catering company, and two food samples collected from the
      catering company were positive for SE. Foods likely were contaminated directly or
      indirectly through the use of illegally sourced, SE-contaminated eggs at the
      implicated catering facility and by catering employees who were infected with SE.
      Public health interventions put into place to control the outbreak included
      screening employees for Salmonella, excluding those infected from food-handling
      duties, and training employees in safe food-handling procedures. No further
      outbreak cases were identified after full implementation of the interventions.
      This investigation highlights the potential for lunch trucks to be a source of
      foodborne illness and the need for robust regulatory compliance monitoring of
      lunch trucks and their food suppliers. 

PMID- 23863704
TI  - Dengue outbreak--Federated States of Micronesia, 2012-2013.
AB  - On September 26, 2012, a woman aged 35 years from Kosrae in the Federated States
      of Micronesia (FSM) was hospitalized with fever, headache, muscle pain, vomiting,
      leukopenia, and thrombocytopenia. A rapid diagnostic test (RDT) (Dengue Duo,
      Standard Diagnostics Inc.) was positive for dengue virus (DENV) nonstructural
      protein-1 (NS1). During the next week, seven more persons with suspected dengue
      were tested with the RDT, of whom three were RDT-positive for NS1 or anti-DENV
      immunoglobulin M (IgM). During October, the Kosrae State Department of Health
      Services, with support from the FSM Department of Health and Social Affairs and
      the World Health Organization (WHO), responded to the outbreak with enhanced
      surveillance, training in clinical management, analysis of hospital surge
      capacity, a rapid mosquito survey to identify species and distributions, and
      control measures. By March 14, 2013, approximately 3.7% of Kosrae State residents
      had been hospitalized with suspected dengue. The outbreak consumed scarce medical
      and public health services, including outpatient, inpatient, and laboratory
      services, resulting in redirection of human and material resources from other
      important medical and public health activities. Because the health consequences
      of dengue can be substantial in resource-limited settings, Pacific Island nations
      might wish to consider preparedness measures for dengue outbreaks such as
      developing and testing outbreak response plans and ensuring adequate capacity for
      epidemiologic surveillance and laboratory testing. 

PMID- 23863705
TI  - Updated recommendations for use of VariZIG--United States, 2013.
AB  - In December 2012, the Food and Drug Administration (FDA) approved VariZIG, a
      varicella zoster immune globulin preparation (Cangene Corporation, Winnipeg,
      Canada) for use in the United States for postexposure prophylaxis of varicella
      for persons at high risk for severe disease who lack evidence of immunity to
      varicella* and for whom varicella vaccine is contraindicated. Previously
      available under an investigational new drug (IND) expanded access protocol,
      VariZIG, a purified immune globulin preparation made from human plasma containing
      high levels of anti-varicella-zoster virus antibodies (immunoglobulin G), is the
      only varicella zoster immune globulin preparation currently available in the
      United States. VariZIG is now approved for administration as soon as possible
      following varicella-zoster virus exposure, ideally within 96 hours (4 days) for
      greatest effectiveness. CDC recommends administration of VariZIG as soon as
      possible after exposure to the varicella-zoster virus and within 10 days. CDC
      also has revised the patient groups recommended by the Advisory Committee on
      Immunization Practices (ACIP) to receive VariZIG by extending the period of
      eligibility for previously recommended premature infants from exposures to
      varicella-zoster virus during the neonatal period to exposures that occur during
      the entire period for which they require hospital care for their prematurity. The
      CDC recommendations for VariZIG use are now harmonized with the American Academy
      of Pediatrics (AAP) recommendations. This report summarizes data on the timing of
      administration of varicella zoster immune globulin in relation to exposure to
      varicella-zoster virus and provides the CDC updated recommendations for use of
      VariZIG that replace the 2007 ACIP recommendations. 

PMID- 23863706
TI  - A 22-year-old professional soccer player with atraumatic ankle pain.

PMID- 23863708
TI  - Rapamycin extends murine lifespan but has limited effects on aging.
AB  - Aging is a major risk factor for a large number of disorders and functional
      impairments. Therapeutic targeting of the aging process may therefore represent
      an innovative strategy in the quest for novel and broadly effective treatments
      against age-related diseases. The recent report of lifespan extension in mice
      treated with the FDA-approved mTOR inhibitor rapamycin represented the first
      demonstration of pharmacological extension of maximal lifespan in mammals.
      Longevity effects of rapamycin may, however, be due to rapamycin's effects on
      specific life-limiting pathologies, such as cancers, and it remains unclear if
      this compound actually slows the rate of aging in mammals. Here, we present
      results from a comprehensive, large-scale assessment of a wide range of
      structural and functional aging phenotypes, which we performed to determine
      whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin
      did extend lifespan, it ameliorated few studied aging phenotypes. A subset of
      aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar
      effects on many of these traits in young animals, indicating that these effects
      were not due to a modulation of aging, but rather related to aging-independent
      drug effects. Therefore, our data largely dissociate rapamycin's longevity
      effects from effects on aging itself. 

PMID- 23863709
TI  - Transcription factor EGR1 directs tendon differentiation and promotes tendon
      repair.
AB  - Tendon formation and repair rely on specific combinations of transcription
      factors, growth factors, and mechanical parameters that regulate the production
      and spatial organization of type I collagen. Here, we investigated the function
      of the zinc finger transcription factor EGR1 in tendon formation, healing, and
      repair using rodent animal models and mesenchymal stem cells (MSCs). Adult
      tendons of Egr1-/- mice displayed a deficiency in the expression of tendon genes,
      including Scx, Col1a1, and Col1a2, and were mechanically weaker compared with
      their WT littermates. EGR1 was recruited to the Col1a1 and Col2a1 promoters in
      postnatal mouse tendons in vivo. Egr1 was required for the normal gene response
      following tendon injury in a mouse model of Achilles tendon healing. Forced Egr1
      expression programmed MSCs toward the tendon lineage and promoted the formation
      of in vitro-engineered tendons from MSCs. The application of EGR1-producing MSCs
      increased the formation of tendon-like tissues in a rat model of Achilles tendon
      injury. We provide evidence that the ability of EGR1 to promote tendon
      differentiation is partially mediated by TGF-beta2. This study demonstrates EGR1
      involvement in adult tendon formation, healing, and repair and identifies Egr1 as
      a putative target in tendon repair strategies. 

PMID- 23863710
TI  - Epigenetic changes induced by adenosine augmentation therapy prevent
      epileptogenesis.
AB  - Epigenetic modifications, including changes in DNA methylation, lead to altered
      gene expression and thus may underlie epileptogenesis via induction of permanent
      changes in neuronal excitability. Therapies that could inhibit or reverse these
      changes may be highly effective in halting disease progression. Here we identify
      an epigenetic function of the brain's endogenous anticonvulsant adenosine,
      showing that this compound induces hypomethylation of DNA via biochemical
      interference with the transmethylation pathway. We show that inhibition of DNA
      methylation inhibited epileptogenesis in multiple seizure models. Using a rat
      model of temporal lobe epilepsy, we identified an increase in hippocampal DNA
      methylation, which correlates with increased DNA methyltransferase activity,
      disruption of adenosine homeostasis, and spontaneous recurrent seizures. Finally,
      we used bioengineered silk implants to deliver a defined dose of adenosine over
      10 days to the brains of epileptic rats. This transient therapeutic intervention
      reversed the DNA hypermethylation seen in the epileptic brain, inhibited
      sprouting of mossy fibers in the hippocampus, and prevented the progression of
      epilepsy for at least 3 months. These data demonstrate that pathological changes
      in DNA methylation homeostasis may underlie epileptogenesis and reversal of these
      epigenetic changes with adenosine augmentation therapy may halt disease
      progression. 

PMID- 23863711
TI  - Isocitrate ameliorates anemia by suppressing the erythroid iron restriction
      response.
AB  - The unique sensitivity of early red cell progenitors to iron deprivation, known
      as the erythroid iron restriction response, serves as a basis for human anemias
      globally. This response impairs erythropoietin-driven erythropoiesis and
      underlies erythropoietic repression in iron deficiency anemia. Mechanistically,
      the erythroid iron restriction response results from inactivation of aconitase
      enzymes and can be suppressed by providing the aconitase product isocitrate.
      Recent studies have implicated the erythroid iron restriction response in anemia
      of chronic disease and inflammation (ACDI), offering new therapeutic avenues for
      a major clinical problem; however, inflammatory signals may also directly repress
      erythropoiesis in ACDI. Here, we show that suppression of the erythroid iron
      restriction response by isocitrate administration corrected anemia and
      erythropoietic defects in rats with ACDI. In vitro studies demonstrated that
      erythroid repression by inflammatory signaling is potently modulated by the
      erythroid iron restriction response in a kinase-dependent pathway involving
      induction of the erythroid-inhibitory transcription factor PU.1. These results
      reveal the integration of iron and inflammatory inputs in a therapeutically
      tractable erythropoietic regulatory circuit. 

PMID- 23863712
TI  - CHIP protects against cardiac pressure overload through regulation of AMPK.
AB  - Protein quality control and metabolic homeostasis are integral to maintaining
      cardiac function during stress; however, little is known about if or how these
      systems interact. Here we demonstrate that C terminus of HSC70-interacting
      protein (CHIP), a regulator of protein quality control, influences the metabolic
      response to pressure overload by direct regulation of the catalytic alpha subunit
      of AMPK. Induction of cardiac pressure overload in Chip-/- mice resulted in
      robust hypertrophy and decreased cardiac function and energy generation stemming
      from a failure to activate AMPK. Mechanistically, CHIP promoted LKB1-mediated
      phosphorylation of AMPK, increased the specific activity of AMPK, and was
      necessary and sufficient for stress-dependent activation of AMPK. CHIP-dependent
      effects on AMPK activity were accompanied by conformational changes specific to
      the alpha subunit, both in vitro and in vivo, identifying AMPK as the first
      physiological substrate for CHIP chaperone activity and establishing a link
      between cardiac proteolytic and metabolic pathways. 

PMID- 23863713
TI  - The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive
      hematopoietic cells.
AB  - Hematopoietic stem progenitor cells (HSPCs) are present in very small numbers in
      the circulating blood in steady-state conditions. In response to stress or
      injury, HSPCs are primed to migrate out of their niche to peripheral blood.
      Mobilized HSPCs are now commonly used as stem cell sources due to faster
      engraftment and reduced risk of posttransplant infection. In this study, we
      demonstrated that a nucleotide sugar, UDP-glucose, which is released into
      extracellular fluids in response to stress, mediates HSPC mobilization. UDP
      glucose-mobilized cells possessed the capacity to achieve long-term repopulation
      in lethally irradiated animals and the ability to differentiate into multi
      lineage blood cells. Compared with G-CSF-mobilized cells, UDP-glucose-mobilized
      cells preferentially supported long-term repopulation and exhibited lymphoid
      biased differentiation, suggesting that UDP-glucose triggers the mobilization of
      functionally distinct subsets of HSPCs. Furthermore, co-administration of UDP
      glucose and G-CSF led to greater HSPC mobilization than G-CSF alone.
      Administration of the antioxidant agent NAC significantly reduced UDP-glucose
      induced mobilization, coinciding with a reduction in RANKL and
      osteoclastogenesis. These findings provide direct evidence demonstrating a
      potential role for UDP-glucose in HSPC mobilization and may provide an attractive
      strategy to improve the yield of stem cells in poor-mobilizing allogeneic or
      autologous donors. 

PMID- 23863714
TI  - Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated
      cholecystokinin secretion.
AB  - Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine
      cells scattered among absorptive cells of the small intestine. CCK is released
      into blood following a meal; however, the mechanisms inducing hormone secretion
      are largely unknown. Ingested fat is the major stimulant of CCK secretion. We
      recently identified a novel member of the lipoprotein remnant receptor family
      known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal
      CCK cells and postulated that this receptor conveyed the signal for fat
      stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK
      cells. Orogastric administration of fatty acids elevated blood levels of CCK in
      wild-type mice but not Ildr1-deficient mice, although the CCK secretory response
      to trypsin inhibitor was retained. The uptake of fluorescently labeled
      lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated
      intestinal cells required a unique combination of fatty acid plus HDL. CCK
      secretion secondary to ILDR1 activation was associated with increased [Ca2+]i,
      consistent with regulated hormone release. These findings demonstrate that ILDR1
      regulates CCK release through a mechanism dependent on fatty acids and
      lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone
      secretion. 

PMID- 23863717
TI  - Sex differences in dreaming during short propofol sedation for upper
      gastrointestinal endoscopy.
AB  - Previous reports suggest that sex differences may exist in dreaming under
      anesthesia, but their results were inconclusive. The current study explored sex
      differences in the incidence and content of dreams during short propofol sedation
      for upper gastrointestinal endoscopy and investigated whether sex differences or
      dream content affect patient satisfaction with sedation. A total of 200 patients
      (100 men and 100 women) undergoing upper gastrointestinal endoscopy participated
      in this study. Patients were interviewed with the modified Brice questionnaire
      about the incidence and the content of dreams, and satisfaction with sedation was
      assessed. The results showed that the incidence of dreaming was significantly
      higher in men (31%) than in women (17%) (P=0.02), but recovery time was similar.
      In men, 45% (14/31) of dreamers reported positive emotional content and only 6%
      (2/31) reported negative emotional content. In contrast, in women, 18% (3/17)
      reported positive and 29% (5/17) reported negative content (P=0.04). Men reported
      dreams that were more vivid, meaningful, familiar, and memorable (P<0.01). No
      significant sex differences were observed in the emotional intensity of dreams,
      and emotional content did not influence patients' satisfaction. In sum, sex
      differences existed in dreaming during short propofol sedation despite similar
      recovery time and matching in terms of age. Men reported dreaming more frequently
      and had a higher incidence of recall for their dream narratives. In particular,
      men reported significantly more positive emotional content, less negative
      emotional content, and more meaningful content. Dreamer satisfaction with
      sedation was not influenced by sex or dream content. 

PMID- 23863715
TI  - Somitic disruption of GNAS in chick embryos mimics progressive osseous
      heteroplasia.
AB  - Progressive osseous heteroplasia (POH) is a rare developmental disorder of
      heterotopic ossification (HO) caused by heterozygous inactivating germline
      mutations in the paternal allele of the GNAS gene. Interestingly, POH lesions
      have a bewildering mosaic distribution. Using clinical, radiographic, and
      photographic documentation, we found that most of the 12 individuals studied had
      a lesional bias toward one side or the other, even showing exclusive sidedness.
      Most strikingly, all had a dermomyotomal distribution of HO lesions. We
      hypothesized that somatic mutations in a progenitor cell of somitic origin may
      act on a background of germline haploinsufficiency to cause loss of
      heterozygosity at the GNAS locus and lead to the unilateral distribution of POH
      lesions. Taking advantage of the chick system, we examined our hypothesis by
      mimicking loss of heterozygosity of GNAS expression using dominant-negative GNAS
      that was introduced into a subset of chick somites, the progenitors that give
      rise to dermis and muscle. We observed rapid ectopic cartilage and bone induction
      at the axial and lateral positions in a unilateral distribution corresponding to
      the injected somites, which suggests that blocking GNAS activity in a targeted
      population of progenitor cells can lead to mosaic ectopic ossification
      reminiscent of that seen in POH. 

PMID- 23863718
TI  - Intra-patient semi-automated segmentation of the cervix-uterus in CT-images for
      adaptive radiotherapy of cervical cancer.
AB  - For online adaptive radiotherapy of cervical cancer, fast and accurate image
      segmentation is required to facilitate daily treatment adaptation. Our aim was
      twofold: (1) to test and compare three intra-patient automated segmentation
      methods for the cervix-uterus structure in CT-images and (2) to improve the
      segmentation accuracy by including prior knowledge on the daily bladder volume or
      on the daily coordinates of implanted fiducial markers. The tested methods were:
      shape deformation (SD) and atlas-based segmentation (ABAS) using two non-rigid
      registration methods: demons and a hierarchical algorithm. Tests on 102 CT-scans
      of 13 patients demonstrated that the segmentation accuracy significantly
      increased by including the bladder volume predicted with a simple 1D model based
      on a manually defined bladder top. Moreover, manually identified implanted
      fiducial markers significantly improved the accuracy of the SD method. For
      patients with large cervix-uterus volume regression, the use of CT-data acquired
      toward the end of the treatment was required to improve segmentation accuracy.
      Including prior knowledge, the segmentation results of SD (Dice similarity
      coefficient 85 +/- 6%, error margin 2.2 +/- 2.3 mm, average time around 1 min)
      and of ABAS using hierarchical non-rigid registration (Dice 82 +/- 10%, error
      margin 3.1 +/- 2.3 mm, average time around 30 s) support their use for image
      guided online adaptive radiotherapy of cervical cancer. 

PMID- 23863716
TI  - Inner ear supporting cells protect hair cells by secreting HSP70.
AB  - Mechanosensory hair cells are the receptor cells of hearing and balance. Hair
      cells are sensitive to death from exposure to therapeutic drugs with ototoxic
      side effects, including aminoglycoside antibiotics and cisplatin. We recently
      showed that the induction of heat shock protein 70 (HSP70) inhibits ototoxic drug
      induced hair cell death. Here, we examined the mechanisms underlying the
      protective effect of HSP70. In response to heat shock, HSP70 was induced in glia
      like supporting cells but not in hair cells. Adenovirus-mediated infection of
      supporting cells with Hsp70 inhibited hair cell death. Coculture with heat
      shocked utricles protected nonheat-shocked utricles against hair cell death. When
      heat-shocked utricles from Hsp70-/- mice were used in cocultures, protection was
      abolished in both the heat-shocked utricles and the nonheat-shocked utricles.
      HSP70 was detected by ELISA in the media surrounding heat-shocked utricles, and
      depletion of HSP70 from the media abolished the protective effect of heat shock,
      suggesting that HSP70 is secreted by supporting cells. Together our data indicate
      that supporting cells mediate the protective effect of HSP70 against hair cell
      death, and they suggest a major role for supporting cells in determining the fate
      of hair cells exposed to stress. 

PMID- 23863719
TI  - Response to Pega, Kawachi, Rasanathan and Lundberg (2013).

PMID- 23863721
TI  - [Clinical features of solid malignant tumors in childhood].
AB  - The pathogenesis of pediatric malignant tumors is associated with congenital
      abnormalities. Oncogenes and antioncogenes are identified in some of these cases.
      Neuroblastoma arises from the adrenal medulla and sympathetic ganglia. Most
      neuroblastomas produce catecholamine. Urinary vanillylmandelic acid(VMA)and
      homovanillic acid(HVA), metabolites of catecholamine, are sensitive tumor
      markers. Risk stratification according to tumor stage and a combination of
      prognostic factors helps determine the appropriate therapeutic strategy in
      clinical settings. Nephroblastoma(Wilms tumor)is the most common pediatric renal
      tumor and is often accompanied by congenital anomalies. Surgical resection of the
      tumor and the involved kidney is the initial treatment recommendation in the US
      and Japan. Consecutive chemotherapy and radiotherapy are administered after
      surgical staging and a definite histopathological diagnosis. Prognosis is
      relatively good for most nephroblastoma cases with a favorable histology. In
      addition to nephroblastoma, clear cell sarcoma of the kidney, characterized by a
      tendency to metastasize to the bone, is a renal tumor with poor prognosis.
      Rhabdoid tumor of the kidney is another tumor type; however, its pathogenesis is
      still unknown and it is associated with extremely poor prognosis because of the
      lack of effective therapeutic measures. Hepatoblastoma is the most common
      malignant liver tumor. The serum alpha-fetoprotein level is the most effective
      tumor marker. Complete surgical resection of the involved liver lobe is the
      definitive approach for cure. Preoperative chemotherapy increases the possibility
      of complete surgical resection. High-risk patients have a poor prognosis. 

PMID- 23863720
TI  - Coordinated regulation of adipose tissue macrophages by cellular and nutritional
      signals.
AB  - The current epidemic of obesity is fueling a global rise in non-communicable
      diseases, including type 2 diabetes mellitus, atherothrombotic disease, and
      cancer. Obesity is associated with systemic inflammation, with various fat
      derived inflammatory factors being implicated in the pathophysiology of insulin
      resistance. The infiltration of various types of inflammatory cells into adipose
      tissue seems to be an important mechanism whereby nutrient excess contributes to
      systemic insulin resistance. In particular, adipose tissue macrophages are
      abundant in obese adipose tissue, and may be the source of the majority of fat
      derived circulating inflammatory factors. This review examines recent studies
      exploring mechanisms whereby cellular and nutritional signals mediate macrophage
      recruitment to adipose tissue and their pro-inflammatory activation. 

PMID- 23863722
TI  - [Recent advances in gastroenteropancreatic neuroendocrine tumor pathology].
AB  - There have been marked advances in clinical and histological aspects GEPNET:
      gastroenteropancreatic neuroendocrine tumor. In particular, histopathological
      classification of GEPNET based on WHO 2010 devided the tumor into three
      histological grades, neuroendocrine tumor(NET)G1, G2 and neuroendocrine
      carcinoma(NEC), exclusively based upon the status of tumor cell proliferation
      determined by mitotic counts and/or the Ki67 labeling index. The clinical
      management of patients with GEPNET must be determined by TNM and the WHO 2010
      classifications. The classifications were proposed based upon the evidences of
      several clinical studies, and it is therefore crucial for clinicians to
      understand the new classifications, for the clinical management of NET patients. 

PMID- 23863723
TI  - [Chemotherapy for GI and pancreatic NETs].
AB  - Neuroendocrine tumors(NETs)describe a heterogeneous group of tumors with a wide
      range of morphologic, functional, and behavioral characteristics. Pancreatic
      neuroendocrine tumors(pNET)are a subset of NETs which are increasing in incidence
      and prevalence. These tumors are generally slow growing and behave in an indolent
      fashion. However, when these tumors spread they can be life threatening and
      difficult to treat with current modalities. Recently, the basic treatment for
      pNET was changed with the approval of two targeted agents, sunitinib and
      everolimus. Clinical trials conducting various combinations of somatostatin
      analogues, mTOR inhibitors, tyrosine kinase inhibitors, and cytotoxic agents are
      ongoing under-evaluation, and a multitargeted approach to therapy will translate
      into improved patient outcomes. 

PMID- 23863724
TI  - [Surgical treatment of gastroentero-pancreatic neuroendocrine tumor].
AB  - The treatment of choice for gastroentero-pancreatic neuroendocrine tumor(NET)is
      resection. Because it is difficult to determine the histological grade of NET
      before operation, the treatment strategy is usually made based on an imaging
      study including the tumor's size. Some selected gastrointestinal NETs are
      indicated for endoscopic resection, while others are resected surgically with
      lymph node dissection. The types of resections for pancreatic NETs vary from
      enucleation to pancreatectomy with or without regional lymph node dissection,
      based on the type of excessive hormone, tumor size, distance from the main
      pancreatic duct, and the presence of type 1 multiple endocrine neoplasia. Hepatic
      metastases are also resected, if indicated, and even in patients having
      unresectable metastatic lesions, multidisciplinary therapy including reduction
      surgery of over 90% of tumor volume might lead to a favorable prognosis.
      Postoperative adjuvant therapy is recommended for neuroendocrine carcinoma, while
      there is no evidence to support adjuvant therapy for curatively resected well
      differentiated NET. 

PMID- 23863725
TI  - [Delay in the introduction of treatment modalities for neuroendocrine tumors in
      Japan].
AB  - The incidence of pancreatic-intestinal neuroendocrine tumors is rapidly
      increasing worldwide, and intensive research has been carried out for the
      standardization of its treatment. In Japan, a few diagnostic and treatment
      modalities including somatostatin receptor scintigraphy(SRS)have not been
      approved by the government. Therefore, we intend to improve this situation as
      soon as possible. 

PMID- 23863726
TI  - [Use of zoledronic acid for lung cancer with bone metastases - a study on
      reossification of osteolytic bone metastases].
AB  - Lung cancer often induces osteolytic bone metastases, and skeletal-related
      events(SRE)such as bone pain or fracture decrease the quality of life and
      survival of the patient. Zoledronic acid(ZDA)suppresses osteoclastic changes and
      reduces the risk of SRE. Over the last 6 years, 84 lung cancer patients who had
      osteolytic bone metastases were medicated with ZDA in our hospital. Effective
      reossification was observed in 25%of them, and they obtained longer survival term
      and better performance status than did patients without effective reossification.
      ZDA enabled enforcement of aggressive anticancer therapy(radiation+/-
      chemotherapy)by reduction of SRE following reossification of osteolytic bone
      metastases, and contributed to better prognoses for lung cancer patients. 

PMID- 23863727
TI  - The clinical benefit of high-dose toremifene for metastatic breast cancer.
AB  - INTRODUCTION: Toremifene(TOR)is a selective estrogen receptor modulator(SERM). A
      high dose of 120 mg TOR(HD-TOR) has been used for recurrent breast cancer in
      Japan, but there is still insufficient evidence regarding the efficacy of HD-TOR.
      PATIENTS AND METHODS: HD-TOR was administered for recurrent or metastatic breast
      cancer between January 2003 and May 2012. The primary end point of the study was
      the tumor response rate. Bone metastasis cases were excluded from the efficacy
      analysis, but were included in the safety population. RESULTS: A total of 21
      patients registered in the study and the 2 patients with bone metastasis only
      were excluded from the efficacy analysis. The median follow-up period was 8. 3
      months. None of the patients in the study had a CR, 4 had a PR(21. 1%), 9 had
      SD(47. 4%), and 6 had PD(31. 6%). Eight of the 9 SD cases had a long-term SD. The
      ORR was 21. 1% and the CB rate was 63. 2%. The median TTP of CB cases was 18. 3
      months. None of the patients discontinued treatment because of a grade 3 or grade
      4 adverse effects. CONCLUSION: In summary, the current study showed that HD-TOR
      may lead to a CB for recurrent breast cancer in first- or second-line treatment
      rather than thirdline. In particular, HD-TOR may give a benefit in highly
      endocrine-sensitive cases.

PMID- 23863728
TI  - [A retrospective study of UFT and oral leucovorin combination adjuvant
      chemotherapy for patients over 76 years old with stage III colon cancer].
AB  - OBJECTIVE: To perform a retrospective analysis of UFT and oral leucovorin
      combination adjuvant chemotherapy for Stage III colon cancer patients over 76
      years old, in order to evaluate both treatment efficacy and toxicity. SUBJECTS:
      Between 2002 and 2011, 333 Stage III colon cancer patients had surgery performed
      in our institute, and we studied 25 of them on our chemotherapy regimen. RESULTS:
      Patients'median age was 78 years old, with 12 men and 13 women. Of all the
      patients, 19 had Stage IIIa and 6 had Stage IIIb. The 3-year disease-free
      survival rates for Stage III and Stage IIIa patients were 65. 1% and 83. 1%,
      respectively, and the 3-year overall survival rate for Stage III was 79. 9%. With
      regard to toxicity, liver function disorder was observed in 8% of the patients,
      being the adverse event that occurred the most, but there was no Grade 3 or 4
      toxicity. CONCLUSION: UFT and oral leucovorin combination adjuvant chemotherapy
      for Stage III colon cancer patients over 76 years showed a good response,
      especially for Stage III a.

PMID- 23863729
TI  - [Primary peritoneal carcinoma - a clinicopathological study of 15 cases].
AB  - This is a retrospective study of fifteen cases of primary peritoneal carcinoma
      who were treated between 2001 and 2010 in our hospital. The median age at the
      time of diagnosis was 63 years(range, 40 to 79 years). Three patients had
      clinical stage II disease, eleven patients had stage III disease, and one patient
      was unstaged. The serum CA125 values at pretreatment were elevated in all
      patients, with a median value of 4,144. 8 U/mL(range, 102. 8 to 23, 611. 0 U/mL).
      Optimal debulking was possible in 9 of the 15 patients. All patients were treated
      with paclitaxel and carboplatin chemotherapy during the preoperative and/or
      postoperative period. All patients at stage II disease were alive without
      evidence of disease at the time of evaluation(2 patients>5 years, 1 patient>3
      years). Four patients with stage III disease had died from the disease less than
      3 years after the first treatment. The results of our study showed poor survival
      for the group with stage III disease, but good survival for the group with stage
      II disease. 

PMID- 23863730
TI  - [Preparation of dealcholized onetaxotere(r), docetaxel injection formulation and
      its pharmacokinetics in rats].
AB  - Onetaxotere(r)(OTAX)injection, which is a docetaxel(DOC)injection formulation,
      cannot be administered to those patients with alcohol intolerance or
      hypersensitivity, because it contains ethanol as a dissolving agent. To broaden
      treatment options for those patients, we tried to eliminate ethanol from OTAX
      injection. Under sterile conditions, dealcoholization was carried out using
      nitrogen gas in a hot water bath at 50 degrees C. By this method, the ethanol
      included in OTAX injection was almost completely removed and DOC in the
      formulation was stable for 28 days. When the dealcoholized or untreated OTAX
      injection was intravenously injected in rats, no significant differences in the
      pharmacokinetic parameters of DOC were observed between those with dealcoholized
      and untreated OTAX injections. It is expected that dealcoholized OTAX may be
      useful in patients with alcohol-related difficulties. 

PMID- 23863731
TI  - [Effect of magnesium supplementation on early-stage hypomagnesemia in patients
      treated with cetuximab].
AB  - Cetuximab is a monoclonal antibody that binds to the EGFR, and is used in
      patients with colorectal cancer. The most common toxicities associated with the
      use of cetuximab are rash and hypomagnesemia. Hypomagnesemia is a major adverse
      event, but it has often been ignored in past studies and its management has not
      been characterized. The aim of this study was to obtain a better understanding of
      the overall incidence of hypomagnesemia and to evaluate the usefulness of our
      original treatment guidelines for hypomagnesemia in patients receiving cetuximab
      based therapy. We investigated 15 patients who were treated with cetuximab(with
      or without combined chemotherapy)between October 2008 and November 2010. Thirteen
      patients developed hypomagnesemia: 11 patients had Grade 1, one patient had Grade
      2, and one patient had severe hypomagnesemia(Grade 3). Grade 1 hypomagnesemia was
      observed after an average of 7. 5+/-4. 8 weeks of treatment. None of the patients
      developed Grade 2 or higher hypomagnesemia after the implementation of our
      treatment guidelines. In conclusion, cetuximab treatment is associated with a
      significant risk of hypomagnesemia. The early monitoring and effective management
      of hypomagnesemia are important for patients receiving cetuximab-based therapy. 

PMID- 23863732
TI  - [Examination of the usefulness of the pharmacists' outpatient clinic for
      treatment with oral molecule-targeting drugs].
AB  - BACKGROUND: In the author's hospital, pharmacists' outpatient clinics were
      initiated in April 2010, and the department of breast surgery there has provided
      guidance on oral anti-cancer medication, but with difficulty in adopting
      proposals for supportive therapy made after the doctor's consultation on the same
      day. Under such circumstances, this study examined methods for conducting
      interviews with patients before the doctor's consultation in cases where oral
      molecular-targeted drugs are necessary. OBJECTIVE: To promote next-generation
      skill-mix team medicine in order to improve the continuity of treatment and
      optimize therapeutic effects. METHODS: Patients being treated with oral molecular
      targeted drugs in Hitachi General Hospital were studied. INTERVENTION: Outcomes
      were assessed through medication-monitoring reports, while conducting a
      questionnaire regarding duties of pharmacists coordinating molecular-targeted
      drugs. RESULTS: Within the study period, 245/259(94. 6%)of proposals for
      prescriptions were adopted in 95 patients, among which 212/245(86. 5%) proposed
      supportive therapy. Improvement in conditions was observed in all patients
      treated with supportive therapy. The mean duration of sorafenib administration
      among 19 patients before and after the pharmacist's intervention was 66+/-20. 3
      and 102+/-30. 8 days, respectively. The main reason for the need of pharmacists
      coordinating molecular-targeted drugs was: security among all patients; "support
      for adverse event management"among all doctors; and "proposals for prescription"
      among all nurses. DISCUSSION: The mean duration of sorafenib administration
      prolonged by the pharmacist's intervention and consequent reduction in side
      effects may have directly improved the continuity of treatment. Furthermore, when
      reflecting on each prescription, the pharmacist's expertise may have facilitated
      pharmacological intervention. In the future, it may also be necessary to promote
      pharmacist-led consultations supporting patients' informed choice of drugs.

PMID- 23863733
TI  - [Combined therapy of lapatinib and capecitabine effective against local
      recurrence of breast cancer].
AB  - A 67-year-old woman after mastectomy was afflicted with local recurrence of left
      breast cancer during adjuvant trastuzumab therapy. Oral administration of
      lapatinib and capecitabine served to distinguish the recurrent tumor and also
      reduce the patient's distressing symptoms. This combined anti-cancer therapy may
      be available for patients with breast cancer for whom trastuzumab therapy was not
      adequately effective. 

PMID- 23863734
TI  - [Administration of low-dose albumin-bound paclitaxel for the treatment of
      advanced and recurrent breast cancer patients].
AB  - A recent foreign clinical trial showed albumin-bound paclitaxel(260mg/m2 tri
      weekly)to have a better response for metastatic breast cancer(MBC)than did
      treatment with paclitaxel alone(175mg/m2 tri-weekly). It was sometimes difficult
      to control the occurrence of side effects, such as neutropenia and neuropathy,
      especially after many treatments. The effect of low-dose albumin-bound
      paclitaxel(180-220mg/m2 tri-weekly)was evaluated in 8 patients with MBC. The
      overall response rate was 62. 5%(CR 1, PR 4), and 2 cases had Grade 3/4
      toxicity(Grade 3 neutropenia); however, all patients were manageable. In
      addition, there was a good response rate(50%, PR 3)among the patients previously
      treated with paclitaxel. Because patient's "care" is as important as the "cure"
      in the treatment of MBC, an effective and well-tolerated regimen is recommended
      for patients with this disease. Low-dose albumin-bound paclitaxel was effective
      with reduced side effects, even after PTX treatment. Therefore, albumin-bound
      paclitaxel may be an optional treatment for MBC after any treatment. 

PMID- 23863735
TI  - [Effect of Japanese traditional medicine, TJ-41, on quality of life of patients
      with non-small cell lung cancer receiving outpatient chemotherapy].
AB  - An increasing number of patients with lung cancer are undergoing outpatient
      chemotherapy. It is very important to maintain good quality of life(QOL)for these
      patients, and Japanese traditional medicine, TJ-41, has been reported to improve
      the QOL of patients with advanced cancer. However, the effect of TJ-41 on
      patients with lung cancer undergoing outpatient chemotherapy is unknown.
      Therefore, we conducted this study. To investigate the factors influencing the
      QOL of these patients, we distributed a QOL questionaire,"The QOL Questionnaire
      for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 11 patients with
      non-small cell lung cancer. The medical factors related to the overall QOL scores
      and other categories, indicating"activity","physical condition","psychological
      condition","social relationships","psychological condition"and"face scale"were
      analyzed. A significant decrease in each of the factors was not observed in this
      study. 

PMID- 23863736
TI  - [A case of a 91-year-old patient with advanced squamous cell lung cancer
      complicated with renal dysfunction successfully treated with trans-arterial chemo
      embolization].
AB  - In 2009, a 91-year-old man with renal dysfunction was detected with a small
      nodule in the left pulmonary field. The nodule was found to have gradually
      increased in size by April, 2010. A trans-bronchial lung biopsy(TBLB)and computed
      tomography( CT)revealed squamous cell lung cancer and stage IV (a tumor was found
      on the right side as well), respectively. Systemic chemotherapy was not
      administered because of the advanced age of the patient and mild renal
      dysfunction. We obtained informed consent from the patient and his family before
      trans-arterial chemo-embolization(TACE)was performed. No side effects were
      observed either during or after treatment. Although his visits to our hospital
      stopped, he sought treatment for a cold 8 months after TACE. CT showed 87%
      shrinkage of the tumor shadow. This method could be a new therapeutic option for
      non-small cell lung cancer with little side effects, particularly in older
      patients or those with pulmonary complications. 

PMID- 23863737
TI  - [A case of advanced gastric cancer with esophageal invasion treated by
      neoadjuvant S-1/CDDP chemotherapy].
AB  - A 75-year-old man was found, by endoscopic examination, to have type 2 advanced
      gastric adenocarcinoma with esophageal invasion in the cardia. Endoscopy and
      other modalities revealed observable esophageal invasion. To minimize surgical
      intervention, we treated him with S-1 and cisplatin as neoadjuvant therapy.
      Treatment was as follows: S-1(80mg/m2)was administered orally for 3 weeks
      followed by 2 weeks of rest, and cisplatin(60mg/m2)was administered by
      intravenous drip on day 8. Two courses of treatment resulted in marked shrinkage
      of the primary lesion and improvement of the esophageal invasion. Total
      gastrectomy with splenectomy, and D2 lymph node dissection were performed with an
      adequately long proximal margin, without thoracotomy. Pathological efficacy was
      Grade 2. At present, 1 year after the operation, the patient presents no evidence
      of a recurrence. We concluded that through neoadjuvant chemotherapy for advanced
      gastric cancer with esophageal invasion, thoracotomy could be avoided, thereby
      reducing risks associated with surgery. 

PMID- 23863738
TI  - [A case of long remission for about 5 years as an outpatient with second-line
      chemotherapy of weekly PTX after palliative distal gastrectomy for pStage IV
      advanced gastric cancer].
AB  - A 59-year-old man underwent palliative distal gastrectomy for Stage IV advanced
      gastric cancer with cytological and histopathological peritoneal dissemination.
      After surgery, he began to receive chemotherapy by S-1 oral administration as an
      outpatient. About one year and 9 months after surgery, cartinomatous peritonitis
      grew, and severe obstruction of gastrojejunostomy and dilatation of residual
      stomach were detected by CT tomography. Then, second-line chemotherapy by weekly
      paclitaxel(PTX)was started. After one course of weekly PTX was completed, he was
      feeling better gradually with obvious improvement of carcinomatous peritonitis,
      which was revealed by sequential CT tomography examinations. Weekly PTX
      chemotherapy has been continued successfully for 43 courses, and he remains alive
      today with a good QOL, about 5 years after surgery. He is an outpatient with only
      a grade 2 or less complication of peripheral neuropathy. 

PMID- 23863739
TI  - [A case of recurrence after resection of gastric cancer successfully treated by
      combination chemotherapy with CPT-11 and CDDP].
AB  - A 62-year-old man received total gastrectomy and splenectomy for gastric cancer
      in April 2008. The pathological diagnosis was stage IIIA(pT3N2M0). After the
      surgery, he was treated with oral administration of S-1 as postoperative adjuvant
      chemotherapy, but stopped after five months because of a drug eruption and
      general fatigue. He visited our hospital with complaints of abdominal pain and
      appetite loss in January 2010. Tumor marker(CEA)was elevated, and he was
      diagnosed as local recurrence with metastasis to the mediastinal/Virchow lymph
      node and thoracic vertebra after several examinations. He started to undergo
      combination chemotherapy with CPT-11 and CDDP. After three courses of treatment,
      local recurrence had almost disappeared and CEA level was normalized. After five
      courses of treatment, FDG-PET showed that all recurrent tumors had decreased in
      size and FDG uptake. We finished this combination chemotherapy after ten courses.
      After the treatment, PET-CT detected a slowly-growing right lung tumor. He
      received S6 segmentectomy of the right lung in May 2012. The pathological
      diagnosis was squamous cell carcinoma, and he was diagnosed as primary lung
      cancer(pT1aN0M0, stage I A). He was followed without showing any recurrence of
      gastric cancer in October 2012. 

PMID- 23863740
TI  - [A case of HER2-positive gastric cancer successfully treated with trastuzumab
      plus capecitabine plus cisplatin chemotherapy as third-line treatment].
AB  - A 67-year-old woman was diagnosed as having advanced gastric cancer(poorly
      differentiated adenocarcinoma)with multiple liver metastases. She had received
      combined S-1 plus cisplatin chemotherapy as first-line treatment and weekly
      paclitaxel chemotherapy as second-line treatment, however, both had eventually
      proved ineffective. Because the gastric cancer was HER2-positive, she was treated
      with trastuzumab plus capecitabine plus cisplatin(XP)chemotherapy as third-line
      treatment. The primary lesion and liver metastatic lesions were confirmed to show
      remarkable regression. The ToGA trial revealed increased efficacy of trastuzumab
      in first-line treatment of cancers showing high expression levels of the HER2-
      protein. This case suggested the increased efficacy of trastuzumab in third-line
      treatment. Neutropenia and hand foot syndrome of grade 2 were all reported
      adverse events. She could receive trastuzumab plus XP chemotherapy safely by dose
      reduction or dormancy temporarily of capecitabine. 

PMID- 23863741
TI  - [A case of a giant rectal gastrointestinal stromal tumor radically resectable
      after treatment with neoadjuvant imatinib mesylate].
AB  - A 64-year-old male patient was diagnosed with rectal gastrointestinal stromal
      tumor(GIST)by prostate biopsy, because of high PSA. We considered that a radical
      operation was impossible because the tumor occupied the pelvis, and we suspected
      prostate invasion. After neoadjuvant chemotherapy(imatinib mesylate 400 mg/day),
      the tumor size was reduced(90*85 mm->60*50mm), and we could thus perform radical
      resection. The patient is currently receiving adjuvant chemotherapy (imatinib
      mesylate 400 mg/day), without recurrence. 

PMID- 23863742
TI  - [A case of metachronous gastrointestinal perforation of a patient with metastatic
      rectal cancer during treatment with bevacizumab-based chemotherapy].
AB  - A 64-year-old man received mFOLFOX6+bevacizumab chemotherapy for metastatic lung
      cancer after rectal cancer resection( Stage IV). After 28 courses, he had an
      abdominal pain with fever, and computed tomography showed pelvic abscess with
      stercolith of appendix. He was diagnosed as acute appendicitis with intra
      abdominal abscess, and emergency appendectomy with drainage was performed. Two
      days after the operation, he was suspected to have a sutural leakage as was
      suggested from the properties of his drainage, therefore re-operation was
      performed. A small hole of the ileum, about 2mm in diameter, was observed. The
      margin of the hole showed neither inflammatory nor neoplastic change, and a
      suturing closure of the hole was performed. The post-operative course was
      uneventful. Histopathological findings of the resected appendix suggested that
      the perforation was caused by necrosis of metastatic cancer cells penetrating the
      appendiceal wall. This is a case of a bevacizumab-related metachronous
      perforation that occurred in different gastrointestinal origins within a very
      short term. 

PMID- 23863743
TI  - [A case of metastatic acsending colon cancer showing sustained complete response
      to chemotherapy with SOX and followed UFT].
AB  - A 72-year-old woman was diagnosed as Stage IV ascending colon cancer, with
      metastasis of lung and para-aortic lymph node. She received laparoscopic assisted
      right hemicolectomy for the local control. After the operation, we performed
      chemotherapy. We report a case of metastatic ascending colon cancer showing
      complete response(CR)to 3 courses of S-1/ oxaliplatin(SOX)regimen, and
      maintaining a CR status while being followed with UFT for 20 months. 

PMID- 23863744
TI  - [Successful treatment of a patient using mFOLFOX6 after laparoscopic surgery for
      rectal cancer with peritoneal dissemination].
AB  - A 58-year-old man underwent laparoscopic surgery for rectal cancer(rectal
      sigmoid)complicated by intestinal obstruction. He had no liver metastasis.
      Although many nodules suspected to have arisen from peritoneal dissemination were
      observed in the pelvic cavity, we performed anterior resection assuming that the
      primary lesion was resectable. The surgical findings were sSE, sN2, sP3, sStage
      IV, and histopathological findings were signet-ring cell carcinoma, pSE, pN2,
      pP+, pStage IV. After 8 courses of adjuvant chemotherapy with modified 5
      fluorouracil/Leucovorin/oxaliplatin(mFOLFOX6), carcinoembryonic antigen(
      CEA)decreased to a normal level, and positron emission tomography-computed
      tomography(PET-CT)showed no abnormal accumulation that suggested metastasis. To
      evaluate the effectiveness of this procedure, laparoscopic peritoneal biopsy was
      performed 5 months after surgery, revealing histopathological disappearance of
      the peritoneal dissemination lesion. The patient has been followed up and has
      been receiving S-1 for 1 year after the first surgery. No evidence of recurrence
      has been observed. 

PMID- 23863745
TI  - [A case of recurrent endometrial carcinoma with pleural effusion maintained long
      SD by pegylated liposomal doxorubicin(PLD)chemotherapy].
AB  - We experienced a case of long SD through the use of pegylated liposomal
      doxorubicin(PLD)chemotherapy for recurrent endometrial carcinoma with pleural
      effusion. The patient was an 82-year-old woman with recurrent endometrial
      carcinoma. At 76 years of age, she underwent extended abdominal hysterectomy,
      bilateral salpingo-oophorectomy and pelvic.paraaortic lymphadenectomy for the
      diagnosis of endometrial carcinoma(serous adenocarcinoma)Stage IIIc. She also
      received adjuvant chemotherapy with paclitaxel(175mg/m2)and carboplatin(AUC 6),
      and radiotherapy. Forty-six months after the first treatment, the tumor marker
      CA125 level was elevated, and recurrent tumors at the vaginal stump and
      peritoneal dissemination were recognized. Then, second-line chemotherapy with
      docetaxel(70mg/m2)and carboplatin(AUC5)were administered, and CR was achieved.
      After 6 months, a second relapse occurred. She felt severe dyspnea from the
      massive pleural effusion, and underwent PLD(40mg/m2)monotherapy to control the
      disease progress and to maintain her quality of life. After 5 courses of PLD
      treatment, the pleural effusion clearly diminished, and the CA125 level
      decreased. The toxicity was generally mild. This case suggests that PLD may be
      one of the promising drugs for recurrent endometrial carcinoma. 

PMID- 23863746
TI  - [Comparison of a safety evaluation between paclitaxel injection NK and Taxol(r)].
AB  - Paclitaxel injection NK(NK)is a generic product containing the same amount of
      ingredients as a Taxol(r)Injection. We examined the safety of NK in clinical
      practice compared to the original drug. Our results suggested that for the cancer
      patient, most safety profiles between NK and the original drug are similar.
      However, patients who received Taxol(r)Injection had significantly more grade 2
      neuropathy compared to those who received NK(p<0. 01). 

PMID- 23863748
TI  - Tracing the genomic ancestry of Peruvians reveals a major legacy of pre-Columbian
      ancestors.
AB  - In order to investigate the underlying genetic structure and genomic ancestry
      proportions of Peruvian subpopulations, we analyzed 551 human samples of 25
      localities from the Andean, Amazonian, and Coastal regions of Peru with a set of
      40 ancestry informative insertion-deletion polymorphisms. Using genotypes of
      reference populations from different continents for comparison, our analysis
      indicated that populations from all 25 Peruvian locations had predominantly
      Amerindian genetic ancestry. Among populations from the Titicaca Lake islands of
      Taquile, Amantani, Anapia, and Uros, and the Yanque locality from the southern
      Peruvian Andes, there was no significant proportion of non-autochthonous genomes,
      indicating that their genetic background is effectively derived from the first
      settlers of South America. However, the Andean populations from San Marcos,
      Cajamarca, Characato and Chogo, and coastal populations from Lambayeque and Lima
      displayed a low but significant European ancestry proportion. Furthermore,
      Amazonian localities of Pucallpa, Lamas, Chachapoyas, and Andean localities of
      Ayacucho and Huancayo displayed intermediate levels of non-autochthonous
      ancestry, mostly from Europe. These results are in close agreement with the
      documented history of post-Columbian immigrations in Peru and with several
      reports suggesting a larger effective size of indigenous inhabitants during the
      formation of the current country's population. 

PMID- 23863747
TI  - Meta-analysis of IDH-mutant cancers identifies EBF1 as an interaction partner for
      TET2.
AB  - Isocitrate dehydrogenase (IDH) genes 1 and 2 are frequently mutated in acute
      myeloid leukaemia (AML), low-grade glioma, cholangiocarcinoma (CC) and
      chondrosarcoma (CS). For AML, low-grade glioma and CC, mutant IDH status is
      associated with a DNA hypermethylation phenotype, implicating altered epigenome
      dynamics in the aetiology of these cancers. Here we show that the IDH variants in
      CS are also associated with a hypermethylation phenotype and display increased
      production of the oncometabolite 2-hydroxyglutarate, supporting the role of
      mutant IDH-produced 2-hydroxyglutarate as an inhibitor of TET-mediated DNA
      demethylation. Meta-analysis of the acute myeloid leukaemia, low-grade glioma,
      cholangiocarcinoma and CS methylation data identifies cancer-specific effectors
      within the retinoic acid receptor activation pathway among the hypermethylated
      targets. By analysing sequence motifs surrounding hypermethylated sites across
      the four cancer types, and using chromatin immunoprecipitation and western
      blotting, we identify the transcription factor EBF1 (early B-cell factor 1) as an
      interaction partner for TET2, suggesting a sequence-specific mechanism for
      regulating DNA methylation. 

PMID- 23863749
TI  - Correcting for differential genotyping error in genetic association analysis.
AB  - Differential genotype error in case-control association studies occurs when cases
      and controls are genotyped under different conditions. Existence of differential
      errors can considerably bias the association test, resulting in inflation of type
      I error and spurious significance. With the availability of high-throughput
      genotyping technologies such as the SNPchip, null markers that are unlinked with
      the disease can be used to correct for the bias caused by differential errors. A
      similar method, known as the genomic control, had been used to correct for
      population stratification in association studies. In this paper, we show that the
      same idea can be used to correct for the bias caused by differential errors,
      under the assumption that the null markers and the candidate marker are subject
      to the same or similar genotyping error model. The variance inflation is shown to
      be minor and the bias in the association test is the major source of type I error
      inflation in the presence of differential errors. Our method centralizes the test
      statistic by deducting the bias estimated from null markers through a quadratic
      regression method, which adjusts for the variability of null marker allele
      frequencies. Simulation results show that the proposed method performs very well
      in correcting for the type I error inflations. 

PMID- 23863750
TI  - Association between serum levels of n-3 polyunsaturated fatty acids and coronary
      plaque detected by coronary computed tomography angiography in patients receiving
      statin therapy.
AB  - BACKGROUND: Intensive lipid-lowering therapy with statins reduces cardiovascular
      events, but residual cardiovascular risks remain. Intake of n-3 polyunsaturated
      fatty acids (PUFAs) has been associated with cardiovascular events. We examined
      the relationships between serum n-3 PUFAs and coronary atherosclerotic findings
      on computed tomography angiography (CTA) in patients undergoing statin treatment.
      METHODS AND RESULTS: We enrolled 172 subjects (mean age: 68.2 years; 64% men)
      prior to statin treatment for 6 months. Serum PUFAs, including eicosapentaenoic
      acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid, were measured. When
      the patients were divided into 2 groups according to the median EPA level (61.3
      MUg/ml), the low-EPA group showed higher incidences of 3-vessel plaque
      involvement (62% vs. 43%, P=0.015), noncalcified plaques (NCPs) (74% vs. 52%,
      P=0.0016), extensive NCPs (>= 2 segments) (56% vs. 34%, P=0.0036), and high-risk
      plaques (minimum CT density <39 HU and remodeling index >1.05) (43% vs. 22%,
      P=0.0034). Multivariate analyses revealed that low EPA levels were an independent
      factor for these coronary plaque findings. The DHA levels were not independently
      associated with these findings. CONCLUSIONS: Low serum EPA level, but not serum
      DHA, is associated with the presence and extent of NCPs and high-risk plaques
      detected by coronary CTA in patients undergoing lipid-lowering therapy with
      statins. 

PMID- 23863751
TI  - Biochemical and physiological regulation of cardiac myocyte contraction by
      cardiac-specific myosin light chain kinase.
AB  - Cardiac-specific myosin light chain kinase (cMLCK) is the kinase predominantly
      responsible for the maintenance of the basal level of phosphorylation of cardiac
      myosin light chain 2 (MLC2), which it phosphorylates at Ser-15. This
      phosphorylation repels the myosin heads from the thick myosin filament and moves
      them toward the thin actin filament. Unlike smooth muscle cells, MLC2
      phosphorylation in striated muscle cells appears to be a positive modulator of
      Ca(2+) sensitivity that shifts the Ca(2+)-force relationship toward the left and
      increases the maximal force response and thus does not initiate muscle
      contraction. Recent studies have revealed an increasing number of details of the
      biochemical, physiological, and pathophysiological characteristics of cMLCK. The
      combination of recent technological advances and the discovery of a novel class
      of biologically active nonstandard peptides will hopefully translate into the
      development of drugs for the treatment of heart diseases.

PMID- 23863752
TI  - Health professional consultation and use of conservative management strategies in
      patients with knee or hip osteoarthritis awaiting orthopaedic consultation.
AB  - The aim of this study was to determine the extent to which patients with hip and
      knee osteoarthritis (OA) referred for orthopaedic consultation at a large
      Australian public hospital reported using conservative management strategies as
      recommended by current practice guidelines. A therapist-assisted questionnaire
      was employed within the context of a standard physiotherapy assessment in a
      consecutive cohort of patients with hip or knee OA. Two hundred and two patients
      with hip or knee OA comprised the included sample. Thirty-nine percent (n=79)
      reported having only previously consulted their general practitioner. Only 20%
      (n=41) felt that they had been sufficiently educated about the diagnosis, their
      treatment options and prognosis. Thirty-three percent (n=66) had not previously
      engaged in any non-pharmacological management strategy considered a core clinical
      practice guideline recommendation. The findings of this study suggest that
      several inconsistencies may exist between current Australian clinical practice
      and OA clinical guideline recommendations. Identification of the barriers to the
      use of conservative management requires timely investigation coupled with a
      national implementation framework to support the translation of guideline
      recommendations into practice. 

PMID- 23863753
TI  - The invisible gorilla strikes again: sustained inattentional blindness in expert
      observers.
AB  - Researchers have shown that people often miss the occurrence of an unexpected yet
      salient event if they are engaged in a different task, a phenomenon known as
      inattentional blindness. However, demonstrations of inattentional blindness have
      typically involved naive observers engaged in an unfamiliar task. What about
      expert searchers who have spent years honing their ability to detect small
      abnormalities in specific types of images? We asked 24 radiologists to perform a
      familiar lung-nodule detection task. A gorilla, 48 times the size of the average
      nodule, was inserted in the last case that was presented. Eighty-three percent of
      the radiologists did not see the gorilla. Eye tracking revealed that the majority
      of those who missed the gorilla looked directly at its location. Thus, even
      expert searchers, operating in their domain of expertise, are vulnerable to
      inattentional blindness. 

PMID- 23863754
TI  - Rituals enhance consumption.
AB  - Four experiments tested the novel hypothesis that ritualistic behavior
      potentiates and enhances ensuing consumption--an effect found for chocolates,
      lemonade, and even carrots. Experiment 1 showed that participants who engaged in
      ritualized behavior, compared with those who did not, evaluated chocolate as more
      flavorful, valuable, and deserving of behavioral savoring. Experiment 2
      demonstrated that random gestures do not boost consumption as much as ritualistic
      gestures do. It further showed that a delay between a ritual and the opportunity
      to consume heightens enjoyment, which attests to the idea that ritual behavior
      stimulates goal-directed action (to consume). Experiment 3 found that performing
      a ritual oneself enhances consumption more than watching someone else perform the
      same ritual, suggesting that personal involvement is crucial for the benefits of
      rituals to emerge. Finally, Experiment 4 provided direct evidence of the
      underlying process: Rituals enhance the enjoyment of consumption because of the
      greater involvement in the experience that they prompt.

PMID- 23863755
TI  - Spatial attention interacts with serial-order retrieval from verbal working
      memory.
AB  - The ability to maintain the serial order of events is recognized as a major
      function of working memory. Although general models of working memory postulate a
      close link between working memory and attention, such a link has so far not been
      proposed specifically for serial-order working memory. The present study provided
      the first empirical demonstration of a direct link between serial order in verbal
      working memory and spatial selective attention. We show that the retrieval of
      later items of a sequence stored in working memory-compared with that of earlier
      items-produces covert attentional shifts toward the right. This observation
      suggests the conceptually surprising notion that serial-order working memory,
      even for nonspatially defined verbal items, draws on spatial attention. 

PMID- 23863756
TI  - The cognitive benefits of movement reduction: evidence from dance marking.
AB  - In a number of domains, humans adopt a strategy of systematically reducing and
      minimizing a codified system of movement. One particularly interesting case is
      "marking" in dance, wherein the dancer performs an attenuated version of the
      choreography during rehearsal. This is ostensibly to save the dancer's physical
      energy, but a number of considerations suggest that it may serve a cognitive
      function as well. In this study, we tested this embodied-cognitive-load
      hypothesis by manipulating whether dancers rehearsed by marking or by dancing
      "full out" and found that performance was superior in the dancers who had marked.
      This finding indicates that marking confers cognitive benefits during the
      rehearsal process, and it raises questions regarding the cognitive functions of
      other movement-reduction systems, such as whispering, gesturing, and
      subvocalizing. In addition, it has implications for a variety of topics in
      cognitive science, including embodied cognition and the nascent fields of dance
      and music cognition. 

PMID- 23863758
TI  - Quantifying the dose-response relationship between circulating folate
      concentrations and colorectal cancer in cohort studies: a meta-analysis based on
      a flexible meta-regression model.
AB  - Most epidemiologic studies on folate intake suggest that folate may be protective
      against colorectal cancer, but the results on circulating (plasma or serum)
      folate are mostly inconclusive. We conducted a meta-analysis of case-control
      studies nested within prospective studies on circulating folate and colorectal
      cancer risk by using flexible meta-regression models to test the linear and
      nonlinear dose-response relationships. A total of 8 publications (10 cohorts,
      representing 3,477 cases and 7,039 controls) were included in the meta-analysis.
      The linear and nonlinear models corresponded to relative risks of 0.96 (95%
      confidence interval (CI): 0.91, 1.02) and 0.99 (95% CI: 0.96, 1.02),
      respectively, per 10 nmol/L of circulating folate in contrast to the reference
      value. The pooled relative risks when comparing the highest with the lowest
      category were 0.80 (95% CI: 0.61, 0.99) for radioimmunoassay and 1.03 (95% CI:
      0.83, 1.22) for microbiological assay. Overall, our analyses suggest a null
      association between circulating folate and colorectal cancer risk. The stronger
      association for the radioimmunoassay-based studies could reflect differences in
      cohorts and study designs rather than assay performance. Further investigations
      need to integrate more accurate measurements and flexible modeling to explore the
      effects of folate in the presence of genetic, lifestyle, dietary, and hormone
      related factors. 

PMID- 23863757
TI  - Prospective study of ultraviolet radiation exposure and mortality risk in the
      United States.
AB  - Geographic variations in mortality rate in the United States could be due to
      several hypothesized factors, one of which is exposure to solar ultraviolet
      radiation (UVR). Limited evidence from previous prospective studies has been
      inconclusive. The association between ambient residential UVR exposure and total
      and cause-specific mortality risks in a regionally diverse cohort (346,615 white,
      non-Hispanic subjects, 50-71 years of age, in the National Institutes of Health
      (NIH)-AARP Diet and Health Study) was assessed, with accounting for individual
      level confounders. UVR exposure (averaged for 1978-1993 and 1996-2005) from
      NASA's Total Ozone Mapping Spectrometer was linked to the US Census Bureau 2000
      census tract of participants' baseline residence. Multivariate-adjusted Cox
      proportional-hazards models were used to estimate hazard ratios and 95%
      confidence intervals. Over 12 years, UVR exposure was associated with total
      deaths (n = 41,425; hazard ratio for highest vs. lowest quartiles (HRQ4 vs. Q1) =
      1.06, 95% confidence interval (CI): 1.03, 1.09; Ptrend < 0.001) and with deaths
      (all Ptrend < 0.05) due to cancer (HRQ4 vs. Q1 = 1.06, 95% CI: 1.02, 1.11),
      cardiovascular disease (HRQ4 vs. Q1 = 1.06, 95% CI: 1.00, 1.12), respiratory
      disease (HRQ4 vs. Q1 = 1.37, 95% CI: 1.21, 1.55), and stroke (HRQ4 vs. Q1 = 1.16,
      95% CI: 1.01, 1.33) but not with deaths due to injury, diabetes, or infectious
      disease. These results suggest that UVR exposure might not be beneficial for
      longevity.

PMID- 23863761
TI  - Real-time monitoring of HIFU treatment using pulse inversion.
AB  - Ultrasound (US) imaging is widely used for the real-time guidance of high
      intensity focused ultrasound (HIFU) treatment at a relatively low cost. However,
      ultrasound image guided HIFU (USgHIFU) is limited in the real-time monitoring of
      HIFU treatment due to the large amplitude HIFU signals received by the US imaging
      transducer. The amplitude of the HIFU scattered signal is generally much higher
      than the amplitude of the pulse-echo signal received by the imaging transducer.
      This creates an interference pattern obscuring the image of the tissue. As such,
      it is difficult to monitor lesion location. This paper proposes a real-time
      monitoring method to be performed concurrently with the HIFU insonation, but
      without HIFU interference, which allows for the improvement of treatment accuracy
      and safety in USgHIFU. The proposed method utilizes the physical properties of
      pulse inversion which is capable of removing the fundamental and odd harmonic
      components of the HIFU interference. Therefore, it is possible to secure the
      desired spectral bandwidth used to construct US images for HIFU treatment
      monitoring. The performance of the proposed method was evaluated through
      experiments with both a bovine serum albumin phantom and a chicken breast. The
      results demonstrated that the proposed method is capable of providing
      interference-free US images, thus successfully allowing for US imaging during
      HIFU treatment. 

PMID- 23863759
TI  - Safety of MF59-adjuvanted influenza vaccination in the elderly: results of a
      comparative study of MF59-adjuvanted vaccine versus nonadjuvanted influenza
      vaccine in northern Italy.
AB  - MF59-adjuvanted trivalent influenza vaccine (Novartis Vaccines and Diagnostics,
      Siena, Italy) has been shown to be more effective than nonadjuvanted vaccine in
      the elderly population. Here we present results from a large-scale,
      observational, noninterventional, prospective postlicensure study that evaluated
      the safety of MF59-adjuvanted vaccine in elderly subjects aged 65 years or more.
      The study was performed in 5 northern Italian health districts during the 2006
      2007, 2007-2008, and 2008-2009 influenza seasons. The choice of vaccine-either
      adjuvanted vaccine or a nonadjuvanted influenza vaccine-was determined by
      individual providers on the basis of local influenza vaccination policy.
      Hospitalizations for potential adverse events of special interest (AESIs) were
      identified from hospital databases and then reviewed against recognized case
      definitions to identify confirmed cases of AESI. Cumulative incidences were
      calculated for AESIs in predefined biologically plausible time windows, as well
      as in a 6-month window following vaccination. During the 3-year study period,
      170,988 vaccine doses were administered to a total of 107,661 persons. Despite
      the large study size, cases of AESI resulting in hospitalization were rare, and
      risks of AESI were similar in both the MF59-adjuvanted and nonadjuvanted
      vaccination groups. In conclusion, similar safety profiles were observed for both
      nonadjuvanted and MF59-adjuvanted seasonal influenza vaccines in elderly
      recipients. 

PMID- 23863760
TI  - Efficient design for Mendelian randomization studies: subsample and 2-sample
      instrumental variable estimators.
AB  - Mendelian randomization (MR) is a method for estimating the causal relationship
      between an exposure and an outcome using a genetic factor as an instrumental
      variable (IV) for the exposure. In the traditional MR setting, data on the IV,
      exposure, and outcome are available for all participants. However, obtaining
      complete exposure data may be difficult in some settings, due to high measurement
      costs or lack of appropriate biospecimens. We used simulated data sets to assess
      statistical power and bias for MR when exposure data are available for a subset
      (or an independent set) of participants. We show that obtaining exposure data for
      a subset of participants is a cost-efficient strategy, often having negligible
      effects on power in comparison with a traditional complete-data analysis. The
      size of the subset needed to achieve maximum power depends on IV strength, and
      maximum power is approximately equal to the power of traditional IV estimators.
      Weak IVs are shown to lead to bias towards the null when the subsample is small
      and towards the confounded association when the subset is relatively large.
      Various approaches for confidence interval calculation are considered. These
      results have important implications for reducing the costs and increasing the
      feasibility of MR studies. 

PMID- 23863762
TI  - Magnetic resonance imaging assessment of cerebral arteriovenous malformation
      obliteration after stereotactic radiosurgery.
AB  - BACKGROUND: Stereotactic radiosurgery is ideal for treating small cerebral
      arteriovenous malformations (AVMs) that are surgically inaccessible. However,
      given the inherent delay of AVM obliteration and the potential for radiosurgical
      failure, detailed evaluation of the neurovascular architecture is necessary to
      monitor persistence of residual flow. Modern imaging systems such as magnetic
      resonance imaging (MRI) and angiography allow clinicians to assess transnidus
      flow after radiosurgical intervention. OBJECTIVE: To determine the accuracy of an
      MRI diagnosis of complete thrombosis and to identify variables that affect the
      precision of MRI assessment. METHODS: One hundred twenty patients were reviewed
      after receiving radiosurgery at the University of Florida from 1990 to 2010. Each
      patient had an MRI demonstrating AVM obliteration and an angiogram either
      confirming or denying AVM thrombosis. RESULTS: MRI correctly predicted complete
      AVM obliteration in 82% of patients. There was a significant correlation between
      AVM volume and MRI accuracy in 2 separate models. In the first model, logistic
      regression analysis revealed a significant linear relationship between the
      natural log of AVM volume and MRI accuracy. The second model showed significant
      evidence of a cutoff point in MRI accuracy near an AVM volume of 2.80 cm(3),
      above which MRI agreement with angiography is 90% and below which MRI agreement
      falls off sharply to remain constant at 70%. CONCLUSION: MRI is a useful
      diagnostic system for assessing AVM obliteration, but its accuracy is inherently
      linked to the nidus volume it is measuring. These results suggest that MRI may be
      able to take on an increasingly independent role in the evaluation of AVM
      regression.

PMID- 23863763
TI  - Relative residence time prolongation in intracranial aneurysms: a possible
      association with atherosclerosis.
AB  - BACKGROUND: Intracranial aneurysms can have atherosclerotic wall properties that
      may be important in predicting aneurysm history or estimating the potential risks
      of surgical treatments. OBJECTIVE: To investigate hemodynamic characteristics of
      atherosclerotic lesions in intracranial aneurysms using computational fluid
      dynamics. METHODS: Intraoperative video recordings of 30 consecutive patients
      with an unruptured middle cerebral artery aneurysm were examined to identify
      atherosclerotic lesions on an aneurysm wall. For computational fluid dynamics
      analyses, geometries of aneurysms and adjacent arteries were reconstructed from 3
      dimensional rotational angiography. Transient simulations were conducted under
      patient-specific pulsatile inlet conditions measured by phase-contrast magnetic
      resonance velocimetry. Three hemodynamic wall parameters were calculated: time
      averaged wall shear stress, oscillatory shear index, and relative residence time
      (RRT). Statistical analyses were performed to discriminate the risk factors of
      atherosclerotic lesion formation. RESULTS: Among 30 aneurysms, 7 atherosclerotic
      lesions with remarkable yellow lipid deposition were identified in 5 aneurysms.
      All 7 atherosclerotic lesions spatially agreed with the area with prolonged RRT.
      Univariate analysis revealed that male sex (P = .03), cigarette smoking (P =
      .047), and maximum RRT (P = .02) are significantly related to atherosclerotic
      lesion on the intracranial aneurysmal wall. Of those variables that influenced
      atherosclerotic lesion of the intracranial aneurysmal wall, male sex (P = .005)
      and maximum RRT (P = .004) remained significant in the multivariate regression
      model. CONCLUSION: The area with prolonged RRT colocalized with atherosclerotic
      change on the aneurysm wall. Male sex and maximum RRT were independent risk
      factors for atherogenesis in intracranial aneurysms.

PMID- 23863764
TI  - Phosphodiesterase 4D single-nucleotide polymorphism 83 and cognitive dysfunction
      in carotid endarterectomy patients.
AB  - BACKGROUND: Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP,
      modulates inflammation and other processes that affect atherosclerosis and
      stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221),
      is associated with ischemic stroke. The association of SNP 83 with postoperative
      cognitive dysfunction has never been investigated. OBJECTIVE: To determine
      whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month
      following carotid endarterectomy (CEA). METHODS: Three hundred fourteen patients
      with high-grade carotid stenosis scheduled for CEA consented to participate in
      this single-center cohort study of cognitive dysfunction. RESULTS: Patients with
      the C/C genotype of SNP 83 exhibited significantly more cognitive dysfunction at
      1 day (29.7%) than the C/T (15.8%, P = .008) and T/T (12.7%, P = .01) genotypes.
      In a multivariate logistic regression model, C/T and T/T genotypes were both
      associated with significantly decreased odds of cognitive dysfunction compared
      with the C/C genotype (odds ratio, 0.45 [0.24-0.83], P = .01 and odds ratio, 0.33
      [0.12-0.77], P = .02). There were no significant associations at 1 month.
      CONCLUSION: The C/C genotype of SNP 83 is significantly associated with the
      highest incidence of cognitive dysfunction 1 day following CEA in comparison with
      the C/T and T/T genotypes. This PDE4D genotype may lead to accelerated cyclic AMP
      degradation and subsequently elevated inflammation 1 day after CEA. These
      observations, in conjunction with previous studies, suggest that elevated
      inflammatory states may be partially responsible for the development of cognitive
      dysfunction after CEA, but more investigation is required.

PMID- 23863765
TI  - Is intraoperative diffusion tensor imaging at 3.0T comparable to subcortical
      corticospinal tract mapping?
AB  - BACKGROUND: Primary brain tumors in motor eloquent areas are associated with high
      risk surgical procedures because of potentially permanent and often disabling
      motor deficits. Intraoperative primary motor cortex mapping and corticospinal
      tract (CST) monitoring are well-developed and reliable techniques. Imaging of the
      CST by diffusion tensor tractography (DTT) is also feasible. OBJECTIVE: To
      evaluate the practical value of 3.0T intraoperative MRI (iMRI) with
      intraoperative DTT (iDTT) in surgery close to the CST, and to compare high-field
      iDTT with intraoperative neurophysiological CST mapping during glioma and
      metastasis resection in a routine setting. METHODS: Twenty-five patients (13
      males, 12 females, median 47 years) were enrolled prospectively from June 2010 to
      June 2012. Patients were included if they had a solitary supratentorial
      intracerebral lesion compressing or infiltrating the CST according to
      preoperative MRI. Subcortical CST mapping was performed by monopolar (cathodal)
      stimulation (500 Hz, 400 MUs, 5 pulses). CST DTT was made both at preoperative
      and intraoperative 3.0T MRI. Subcortical motor-evoked potential threshold current
      and probe-CST distance were recorded at 155 points before and at 103 points after
      iMRI. Current-distance correlations were performed both for pre-iMRI and for post
      iMRI data. RESULTS: The correlation coefficient pre-iMRI was R = 0.470 (P <
      .001); post-iMRI, the correlation coefficient was R = 0.338 (P < .001). MRI
      radical resection was achieved in 17 patients (68%), subtotal in 5 (24%), and
      partial in 3 (12%). Postoperative paresis developed in 8 patients (32%); the
      paresis was permanent in 1 case (4%). CONCLUSION: The linear current-distance
      correlation was found both in pre-iMRI and in post-iMRI data. Intraoperative
      image distortion appeared in 36%. Neurophysiological subcortical mapping remains
      superior to DTT. Combining these 2 methods in selected cases can help increase
      the safety of tumor resection close to the CST.

PMID- 23863766
TI  - National variability in intracranial pressure monitoring and craniotomy for
      children with moderate to severe traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a significant cause of mortality and
      disability in children. Intracranial pressure monitoring (ICPM) and
      craniotomy/craniectomy (CRANI) may affect outcomes. Sources of variability in the
      use of these interventions remain incompletely understood. OBJECTIVE: To analyze
      sources of variability in the use of ICPM and CRANI. METHODS: Retrospective cross
      sectional study of patients with moderate/severe pediatric TBI with the use of
      data submitted to the American College of Surgeons National Trauma Databank.
      RESULTS: We analyzed data from 7140 children at 156 US hospitals during 7
      continuous years. Of the children, 27.4% had ICPM, whereas 11.7% had a CRANI.
      Infants had lower rates of ICPM and CRANI than older children. A lower rate of
      ICPM was observed among children hospitalized at combined pediatric/adult trauma
      centers than among children treated at adult-only trauma centers (relative risk =
      0.80; 95% confidence interval 0.66-0.97). For ICPM and CRANI, 18.5% and 11.6%,
      respectively, of residual model variance was explained by between-hospital
      variation in care delivery, but almost no correlation was observed between within
      hospital tendency toward performing these procedures. CONCLUSION: Infants
      received less ICPM than older children, and children hospitalized at pediatric
      trauma centers received less ICPM than children at adult-only trauma centers. In
      addition, significant between-hospital variability existed in the delivery of
      ICPM and CRANI to children with moderate-severe TBI.

PMID- 23863767
TI  - Commentary: Postsurgical monitoring of acromegaly.

PMID- 23863768
TI  - In reply.

PMID- 23863769
TI  - Surveillance for travel-related disease--GeoSentinel Surveillance System, United
      States, 1997-2011.
AB  - PROBLEM/CONDITION: In 2012, the number of international tourist arrivals
      worldwide was projected to reach a new high of 1 billion arrivals, a 48% increase
      from 674 million arrivals in 2000. International travel also is increasing among
      U.S. residents. In 2009, U.S. residents made approximately 61 million trips
      outside the country, a 5% increase from 1999. Travel-related morbidity can occur
      during or after travel. Worldwide, 8% of travelers from industrialized to
      developing countries report becoming ill enough to seek health care during or
      after travel. Travelers have contributed to the global spread of infectious
      diseases, including novel and emerging pathogens. Therefore, surveillance of
      travel-related morbidity is an essential component of global public health
      surveillance and will be of greater importance as international travel increases
      worldwide. REPORTING PERIOD: September 1997-December 2011. DESCRIPTION OF SYSTEM:
      GeoSentinel is a clinic-based global surveillance system that tracks infectious
      diseases and other adverse health outcomes in returned travelers, foreign
      visitors, and immigrants. GeoSentinel comprises 54 travel/tropical medicine
      clinics worldwide that electronically submit demographic, travel, and clinical
      diagnosis data for all patients evaluated for an illness or other health
      condition that is presumed to be related to international travel. Clinical
      information is collected by physicians with expertise or experience in
      travel/tropical medicine. Data collected at all sites are entered electronically
      into a database, which is housed at and maintained by CDC. The GeoSentinel
      network membership program comprises 235 additional clinics in 40 countries on
      six continents. Although these network members do not report surveillance data
      systematically, they can report unusual or concerning diagnoses in travelers and
      might be asked to perform enhanced surveillance in response to specific health
      events or concerns. RESULTS: During September 1997-December 2011, data were
      collected on 141,789 patients with confirmed or probable travel-related
      diagnoses. Of these, 23,006 (16%) patients were evaluated in the United States,
      10,032 (44%) of whom were evaluated after returning from travel outside of the
      United States (i.e., after-travel patients). Of the 10,032 after-travel patients,
      4,977 (50%) were female, 4,856 (48%) were male, and 199 (2%) did not report sex;
      the median age was 34 years. Most were evaluated in outpatient settings (84%),
      were born in the United States (76%), and reported current U.S. residence (99%).
      The most common reasons for travel were tourism (38%),
      missionary/volunteer/research/aid work (24%), visiting friends and relatives
      (17%), and business (15%). The most common regions of exposure were Sub-Saharan
      Africa (23%), Central America (15%), and South America (12%). Fewer than half
      (44%) reported having had a pretravel visit with a health-care provider. Of the
      13,059 diagnoses among the 10,032 after-travel patients, the most common
      diagnoses were acute unspecified diarrhea (8%), acute bacterial diarrhea (5%),
      postinfectious irritable bowel syndrome (5%), giardiasis (3%), and chronic
      unknown diarrhea (3%). The most common diagnostic groupings were acute diarrhea
      (22%), nondiarrheal gastrointestinal (15%), febrile/systemic illness (14%), and
      dermatologic (12%). Among 1,802 patients with febrile/systemic illness diagnoses,
      the most common diagnosis was Plasmodium falciparum malaria (19%). The rapid
      communication component of the GeoSentinel network has allowed prompt responses
      to important health events affecting travelers; during 2010 and 2011, the
      notification capability of the GeoSentinel network was used in the identification
      and public health response to East African trypanosomiasis in Eastern Zambia and
      North Central Zimbabwe, P. vivax malaria in Greece, and muscular sarcocystosis on
      Tioman Island, Malaysia. INTERPRETATION: The GeoSentinel Global Surveillance
      System is the largest repository of provider-based data on travel-related
      illness. Among ill travelers evaluated in U.S. GeoSentinel sites after returning
      from international travel, gastrointestinal diagnoses were most frequent,
      suggesting that U.S. travelers might be exposed to unsafe food and water while
      traveling internationally. The most common febrile/systemic diagnosis was P.
      falciparum malaria, suggesting that some U.S. travelers to malarial areas are not
      receiving or using proper malaria chemoprophylaxis or mosquito-bite avoidance
      measures. The finding that fewer than half of all patients reported having made a
      pretravel visit with a health-care provider indicates that a substantial portion
      of U.S. travelers might not be following CDC travelers' health recommendations
      for international travel. PUBLIC HEALTH ACTION: GeoSentinel surveillance data
      have helped researchers define an evidence base for travel medicine that has
      informed travelers' health guidelines and the medical evaluation of ill
      international travelers. These data suggest that persons traveling
      internationally from the United States to developing countries remain at risk for
      illness. Health-care providers should help prepare travelers properly for safe
      travel and provide destination-specific medical evaluation of returning ill
      travelers. Training for health-care providers should focus on preventing and
      treating a variety of travel-related conditions, particularly traveler's diarrhea
      and malaria.

PMID- 23863770
TI  - Stability-indicating UPLC method for determining related substances and
      degradants in dronedarone.
AB  - A simple, sensitive and reproducible method was developed on ultra-performance
      liquid chromatography coupled with photodiode array detection for the
      quantitative determination of dronedarone hydrochloride (DRO) in drug substance
      and pharmaceutical dosage forms. The method is applicable for the quantification
      of related substances and assays of drug substances. Chromatographic separation
      was achieved on Acquity UPLC BEH C8 100 mm, 2.1 mm and 1.7 um columns, using
      gradient elution within a short run time of 10.0 min. The eluted compounds were
      monitored at 288 nm, the flow rate was 0.5 mL/min and the column oven temperature
      was maintained at 40 degrees C. The resolution of DRO and 11 impurities
      (potentials and by-products) was greater than 2.0 for all pairs of components.
      The high correlation coefficient value (>0.9995) indicates the clear correlations
      between the concentrations of investigated compound and their peak areas within
      the test ranges. The repeatability and intermediate precision, expressed by the
      relative standard deviation, were less than 2.5%. The accuracy and validity of
      the method were further ascertained by performing recovery studies via a spike
      method. The accuracy of the method, expressed as relative error, was
      satisfactory. No interference was observed from concomitant substances normally
      added to the tablets. DRO was subjected to the stress conditions of oxidative,
      acid, base, hydrolytic, thermal and photolytic degradation. DRO was found to
      degrade significantly in acid and base stress conditions and to remain stable in
      thermal, photolytic degradation, oxidative and hydrolytic conditions. The
      degradation products were well resolved from primary peak and its impurities,
      proving that the method is stability indicating. The developed method was
      validated as per International Conference on Harmonization guidelines with
      respect to specificity, limit of detection, limit of quantification, linearity,
      accuracy, precision, solution stability and robustness. This method is also
      suitable for the determination of DRO drug substance and pharmaceutical dosage
      forms. 

PMID- 23863771
TI  - Intermittent versus continuous central administration of clozapine in DBA/2 mice,
      improvement in sensory inhibition deficits.
AB  - Deficient sensory inhibition, the failure to inhibit responses to repeated
      stimuli, is a hallmark of schizophrenia, and is thought to be related to
      difficulties with attention and working memory. Sensory inhibition is assessed by
      comparing the auditory-evoked EEG responses to 2 closely-spaced identical
      stimuli. Normal individuals show suppressed response to the second stimulus while
      schizophrenia patients have responses of similar magnitude to both stimuli. This
      deficit has been linked to polymorphisms in the promoter for the alpha7 nicotinic
      receptor gene, resulting in reduced numbers of receptors on hippocampal
      interneurons. This deficit is modeled in DBA/2 mice which also show a
      polymorphism in the promoter for the alpha7 nicotinic receptor gene and reduced
      numbers of hippocampal alpha7 receptors. Systemic administration of clozapine,
      the most efficacious antipsychotic medication, improves sensory inhibition
      deficits in both schizophrenia patients and DBA/2 mice. We have previously shown
      that acute intracerebroventricular (ICV) injections of clozapine induced similar
      improvement in sensory inhibition in DBA/2 mice. Here we demonstrate the efficacy
      of chronic ICV clozapine administration in improving sensory inhibition in DBA2
      mice. Mice received ICV vehicle, 3, 7.5, 15 or 30 MUg of clozapine, either
      continuously or as a once-per-day injection. Mice were recorded on the 7th day of
      drug delivery. Both approaches produced improved sensory inhibition, but the
      daily bolus injection was effective at a lower dose (3 MUg/day) than the
      continuous delivery (15 MUg/day). The bolus injections also showed significant
      improvement up to 36 h post injection thus suggesting that this approach may be
      more efficacious.

PMID- 23863772
TI  - What are the neurocognitive correlates of basic self-disturbance in
      schizophrenia? Integrating phenomenology and neurocognition: Part 2 (aberrant
      salience).
AB  - Phenomenological research indicates that disturbance of the basic sense of self
      may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self
      disturbance refers to disruption of the sense of ownership of experience and
      agency of action and is associated with a variety of anomalous subjective
      experiences. Little is known about the neurocognitive underpinnings of basic self
      disturbance. In these two theoretical papers (of which this is Part 2), we review
      some recent phenomenological and neurocognitive research and point to a
      convergence of these approaches around the concept of self-disturbance.
      Specifically, we propose that subjective anomalies associated with basic self
      disturbance may be associated with: 1. source monitoring deficits, which may
      contribute particularly to disturbances of "ownership" and "mineness" (the
      phenomenological notion of presence or self-affection) and 2. aberrant salience,
      and associated disturbances of memory, prediction and attention processes, which
      may contribute to hyper-reflexivity, disturbed "grip" or "hold" on perceptual and
      conceptual fields, and disturbances of intuitive social understanding ("common
      sense"). In this paper (Part 2) we focus on aberrant salience. Part 1 (this
      issue) addressed source monitoring deficits. Empirical studies are required in a
      variety of populations in order to test these proposed associations between
      phenomenological and neurocognitive aspects of self-disturbance in schizophrenia.
      An integration of findings across the phenomenological and neurocognitive
      "levels" would represent a significant advance in the understanding of
      schizophrenia and possibly enhance early identification and intervention
      strategies. 

PMID- 23863773
TI  - Factors influencing the antifolate activity of synthetic tea-derived catechins.
AB  - Novel tea catechin derivatives have been synthesized, and a structure-activity
      study, related to the capacity of these and other polyphenols to bind
      dihydrofolate reductase (DHFR), has been performed. The data showed an effective
      binding between all molecules and the free enzyme, and the dissociation constants
      of the synthetic compounds and of the natural analogues were on the same order.
      Polyphenols with a catechin configuration were better DHFR inhibitors than those
      with an epicatechin configuration. Antiproliferative activity was also studied in
      cultured tumour cells, and the data showed that the activity of the novel
      derivatives was higher in catechin isomers. Derivatives with a hydroxyl group
      para on the ester-bonded gallate moiety presented a high in vitro binding to
      DHFR, but exhibited transport problems in cell culture due to ionization at
      physiologic pHs. The impact of the binding of catechins to serum albumin on their
      biological activity was also evaluated. The information provided in this study
      could be important for the design of novel medicinal active compounds derived
      from tea catechins. The data suggest that changes in their structure to avoid
      serum albumin interactions and to facilitate plasmatic membrane transport are
      essential for the intracellular functions of catechins. 

PMID- 23863774
TI  - HPLC analysis of phenolics compounds and antioxidant capacity of leaves of Vitex
      megapotamica (Sprengel) Moldenke.
AB  - Vitex megapotamica (Sprengel) Moldenke belongs to the Verbenaceae family and is
      popularly known as "taruma". The antioxidant capacity of fractions and crude
      extract from the leaves of V. megapotamica were determined in this study through
      the capacity to remove reactive species and phenolic compounds were quantified in
      the various fractions. The IC50 (DPPH) ranged from 14.17 +/- 0.76 to 37.63 +/-
      0.98 ug/mL. The ethyl acetate fraction might contain the strongest lipid
      peroxidation inhibitory compounds with an IC50 of 16.36 +/- 5.09 ug/mL, being
      also the one with the highest content of polyphenols (522.4 +/- 1.12 mg/g),
      flavonoids (220.48 +/- 0.30 mg/g) and condensed tannins (3.86 +/- 0.53 mg/g).
      Compounds quantified by HPLC/DAD in the crude extract and fractions were
      chlorogenic and rosmarinic acids. Higher dosages of the extracts were more
      effective in reducing levels of plasma protein carbonyls and were also shown to
      be able to remove reactive species by a 2',7'-dichlorofluorescein diacetate
      assay, reducing oxidative stress in all tested fractions. Results obtained
      indicated that V. megapotamica exhibits good potential to prevent diseases caused
      by the overproduction of free radicals and it might also be used as a potential
      source of natural antioxidant agents. 

PMID- 23863775
TI  - Thermal behavior of pinan-2-ol and linalool.
AB  - Linalool is an important intermediate for syntheses of isoprenoid fragrance
      compounds and vitamins A and E. One process option for its production is the
      thermal gas-phase isomerization of cis- and trans-pinan-2-ol. Investigations of
      this reaction were performed in a flow-type apparatus in a temperature range from
      350-600  degrees C and a residence time range of 0.6-0.8 s. Rearrangement of the
      bicyclic alcohol led to linalool, plinols arising from consecutive reactions of
      linalool and other side products. Effects of residence time, temperature, surface
      to-volume-ratio, carrier gas, and the presence of additives on yield and
      selectivity were studied. Furthermore, the effects of such parameters on ene
      cyclization of linalool affording plinols were investigated. Results indicate
      that manipulation of the reaction in order to affect selectivity is difficult due
      to the large free path length to other molecules in the gas phase. However,
      conditions have been identified allowing one to increase the selectivity and the
      yield of linalool throughout pyrolysis of pinan-2-ol. 

PMID- 23863776
TI  - Development of 65 novel polymorphic cDNA-SSR markers in common vetch (Vicia
      sativa subsp. sativa) using next generation sequencing.
AB  - Vetch (Vicia sativa L.) is one of the most important annual forage legumes in the
      World due to its multiple uses (i.e., hay, grain, silage and green manure) and
      high nutritional value. However, detrimental cyanoalanine toxins in its plant
      parts including seeds and its vulnerability to hard winter conditions are
      currently reducing the agronomic values of vetch varieties. Moreover, the
      existence in the public domain of very few genomic resources, especially
      molecular markers, has further hampered breeding efforts. Polymorphic simple
      sequence repeat markers from transcript sequences (cDNA; simple sequence repeat
      [SSR]) were developed for Vicia sativa subsp. sativa. We found 3,811 SSR loci
      from 31,504 individual sequence reads, and 300 primer pairs were designed and
      synthesized. In total, 65 primer pairs were found to be consistently scorable
      when 32 accessions were tested. The numbers of alleles ranged from 2 to 19,
      frequency of major alleles per locus were 0.27-0.87, the genotype number was 2
      19, the overall polymorphism information content (PIC) values were 0.20-0.86, and
      the observed and expected heterozygosity values were 0.00-0.41 and 0.264-0.852,
      respectively. These markers provide a useful tool for assessing genetic
      diversity, population structure, and positional cloning, facilitating vetch
      breeding programs. 

PMID- 23863777
TI  - Distinct metabolites for photoreactive L-phenylalanine derivatives in Klebsiella
      sp. CK6 isolated from rhizosphere of a wild dipterocarp sapling.
AB  - Photoaffinity labeling is a reliable analytical method for biological functional
      analysis. Three major photophores--aryl azide, benzophenone and
      trifluoromethyldiazirine--are utilized in analysis. Photophore-bearing L
      phenylalanine derivatives, which are used for biological functional analysis,
      were inoculated into a Klebsiella sp. isolated from the rhizosphere of a wild
      dipterocarp sapling in Central Kalimantan, Indonesia, under nitrogen-limiting
      conditions. The proportions of metabolites were quite distinct for each
      photophore. These results indicated that photophores affected substrate
      recognition in rhizobacterial metabolic pathways, and differential photoaffinity
      labeling could be achieved using different photophore-containing L-phenylalanine
      derivatives.

PMID- 23863778
TI  - Characterization of flavonoids and phenolic acids in Myrcia bella Cambess. using
      FIA-ESI-IT-MS(n) and HPLC-PAD-ESI-IT-MS combined with NMR.
AB  - The leaves of Myrcia DC. ex Guill species are used in traditional medicine and
      are also exploited commercially as herbal drugs for the treatment of diabetes
      mellitus. The present work aimed to assess the qualitative and quantitative
      profiles of M. bella hydroalcoholic extract, due to these uses, since the
      existing legislation in Brazil determines that a standard method must be
      developed in order to be used for quality control of raw plant materials. The
      current study identified eleven known flavonoid-O-glycosides and six acylated
      flavonoid derivatives of myricetin and quercetin, together with two kaempferol
      glycosides and phenolic acids such as caffeic acid, ethil galate, gallic acid and
      quinic acid. In total, 24 constituents were characterized, by means of extensive
      preparative chromatographic analyses, along with MS and NMR techniques. An HPLC
      PAD-ESI-IT-MS and FIA-ESI-IT-MS(n) method were developed for rapid identification
      of acylated flavonoids, flavonoid-O-glycosides derivatives of myricetin and
      quercetin and phenolic acids in the hydroalcoholic M. bella leaves extract. The
      FIA-ESI-IT-MS techinique is a powerful tool for direct and rapid identification
      of the constituents after isolation and NMR characterization. Thus, it could be
      used as an initial method for identification of authentic samples concerning
      quality control of Myrcia spp extracts.

PMID- 23863779
TI  - Characterization of water extractable arabinoxylans from a spring wheat flour:
      rheological properties and microstructure.
AB  - In the present study water extractable arabinoxylans (WEAX) from a Mexican spring
      wheat flour (cv. Tacupeto F2001) were isolated, characterized and gelled and the
      gel rheological properties and microstructure were investigated. These WEAX
      presented an arabinose to xylose ratio of 0.66, a ferulic acid and diferulic acid
      content of 0.526 and 0.036 ug/mg WEAX, respectively and a Fourier Transform Infra
      Red (FT-IR) spectrum typical of arabinoxylans. The intrinsic viscosity and
      viscosimetric molecular weight values for WEAX were 3.5 dL/g and 504 kDa,
      respectively. WEAX solution at 2% (w/v) formed gels induced by a laccase as cross
      linking agent. Cured WEAX gels registered storage (G') and loss (G'') modulus
      values of 31 and 5 Pa, respectively and a diferulic acid content of 0.12 ug/mg
      WEAX, only traces of triferulic acid were detected. Scanning electron microscopy
      analysis of the lyophilized WEAX gels showed that this material resembles that of
      an imperfect honeycomb. 

PMID- 23863780
TI  - Tako-tsubo cardiomyopathy and coronary artery disease: a possible association.
AB  - BACKGROUND: In the medical literature, several cases of Tako-tsubo cardiomyopathy
      (TTC) with coronary artery disease (CAD) have been reported, and in clinical
      practice, several typical TTC cases show relevant stenoses of the coronary
      arteries spatially unrelated to the dysfunctional myocardium. OBJECTIVE: This
      study aimed to evaluate the prevalence, clinical characteristics, and outcome of
      patients with TTC and relevant CAD in a large multicenter database. METHODS: In
      26 centers, 450 patients admitted with a diagnosis of TTC underwent coronary
      angiography within 48 h of hospital admission and were included prospectively in
      the Tako-tsubo Italian Network Registry. RESULTS: Overall, 43 (9.6%) patients had
      at least one relevant (>=50%) coronary stenosis not supplying the dysfunctional
      myocardium, whereas 407 patients (90.4%) had irrelevant stenosis or
      angiographically normal coronary arteries. TTC patients with relevant CAD were
      more likely to be older in age, to have diabetes, a familial history of CAD, and
      acute functional mitral regurgitation compared with those without relevant CAD.
      At the 6-month follow-up, the incidence of death, TTC recurrence, and
      rehospitalization rates in patients with and without relevant CAD were similar.
      On multivariable Cox analysis, an independent predictor of death was the Charlson
      Comorbidity Index, whereas the presence of CAD did not influence the mid-term
      outcome significantly. CONCLUSION: The presence of CAD is a rather common finding
      in a large proportion of patients with TTC. Thus, when the stenotic artery does
      not supply the dysfunctional myocardium or when the extent of dysfunctional
      myocardium is wider than the territory of distribution supplied by a single
      stenotic coronary artery, the presence of angiographically relevant CAD should
      not be considered an exclusion criterion for TTC.

PMID- 23863781
TI  - Bioresorbable polystatin fourth-generation stents.
AB  - OBJECTIVE: Stents have evolved through three generations, the latest of which are
      totally bioresorbable to include drugs targeting restenosis, the surface polymer
      eluting those drugs, and scaffolds on which those drugs are coated. These
      scaffolds, however, thus far, have been pharmacologically inactive and remain a
      potential site for delivering a second drug. Therefore, we sought to evaluate the
      possibility of modifying a bioresorbable polymer so that it can double as a
      scaffold for both a stent and a drug targeting impaired re-endothelialization and
      stent thrombosis. METHODS AND RESULTS: We successfully modified a standard
      bioresorbable terpolymer in a way found to be consistent with the covalent
      incorporation of lovastatin, as seen on NMR, into a backbone comprised of
      lactide, glycolide, epsilon-caprolactone, and lovastatin (60 : 15 : 10 : 15 parts
      by weight), respectively. This was accomplished through a reaction of the four
      components of the polymer at 100 degrees C for 18 h in the presence of an alcohol
      initiator and a scandium catalyst. The resulting terpolymer was fabricated into a
      scaffold using a novel RSF system developed by 3D Biotek. CONCLUSION: It
      preliminarily appears feasible to fabricate a fourth-generation bioresorbable
      stent that has the potential to deliver two drugs to the site of the procedure
      related vessel lumen injury.

PMID- 23863782
TI  - Spectral-domain optical coherence tomography of retinal nerve fiber layer
      thickness in NMO patients.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is a demyelinating syndrome of the central
      nervous system. NMO might be underdiagnosed at early stages when patients have
      not yet developed the full spectrum of disease. The aim of this study was to
      analyze the retinal nerve fiber layer (RNFL) with optical coherence tomography
      (OCT) and to compare RNFL measurements between NMO patients, patients with
      relapsing-remitting multiple sclerosis (RRMS), and healthy controls to determine
      whether differences in RNFL thickness could be an early diagnostic marker for
      NMO. METHODS: In a cross-sectional study, eyes of 25 NMO patients, 25 RRMS
      patients, and 50 healthy controls underwent RNFL measurements by OCT. Clinical
      parameters were collected by history and chart review. Pairwise Wilcoxon rank sum
      tests with Holm correction were used to compare means of RNFL thickness among 6
      groups (NMO, RRMS, and healthy control) of patients [without or with 1 or more
      episode of optic neuritis (ON)]. The association between RNFL thickness and
      patient characteristics for NMO group was examined via linear mixed-effects
      models (adjusting for within-patient intereye correlations and history of ON,
      where appropriate). RESULTS: Based on the pairwise Wilcoxon rank sum tests with
      Holm correction, significant differences were found between NMO with 1 episode of
      ON and non-ON eyes (mean RNFL 63.7 vs 97.0 um, P < 0.0001), multiple sclerosis
      (MS) non-ON eyes, and controls (RNFL 93.2 vs 98.4 um, P = 0.03). No significant
      differences were found between NMO and MS with 1 attack of ON eyes (RNFL 63.7 vs
      73.9 um, P = 0.46), NMO non-ON eyes and healthy controls (RNFL 97.0 vs 98.4 um, P
      = 0.56), and NMO non-ON and MS non-ON (RNFL 97.0 vs 93.2 um, P = 0.56). For NMO
      group, RNFL thickness was associated with a history of ON (P < 0.001) but not
      with disability or disease duration when adjusting for the history of ON (P >
      0.1). CONCLUSIONS: RNFL in NMO is not different enough to distinguish NMO ON from
      MS ON eyes, but the intereye difference in RFNL with a history of unilateral ON
      may be a better diagnostic marker for NMO.

PMID- 23863783
TI  - Translocation and fidelity of Escherichia coli RNA polymerase.
AB  - Exonuclease (exo) III was used as a probe of the Escherichia coli RNA polymerase
      (RNAP) ternary elongation complex (TEC) downstream border. In the absence of
      NTPs, RNAP appears to stall primarily in a post-translocated state and to return
      slowly to a pre-translocated state. Exo III mapping, therefore, appears
      inconsistent with an unrestrained thermal ratchet model for translocation, in
      which RNAP freely and rapidly oscillates between pre- and post-translocated
      positions. The forward translocation state is made more stable by lowering the pH
      and/or by elevating the salt concentration, indicating a probable role of
      protonated histidine(s) in regulating accurate NTP loading and translocation.
      Because the post-translocated TEC can be strongly stabilized by NTP addition, NTP
      analogs were ranked for their ability to preserve the post-translocation state,
      giving insight into RNAP fidelity. Effects of NTPs (and analogs) and analysis of
      chemically modified RNA 3' ends demonstrate that patterns of exo III mapping
      arise from intrinsic and subtle alterations at the RNAP active site, far from the
      site of exo III action. 

PMID- 23863784
TI  - Regulatory interplay between TFIID's conformational transitions and its modular
      interaction with core promoter DNA.
AB  - Recent structural and biochemical studies of human TFIID have significantly
      increased our understanding of the mechanisms underlying the recruitment of TFIID
      to promoter DNA and its role in transcription initiation. Structural studies
      using cryo-EM revealed that modular interactions underlie TFIID's ability to bind
      simultaneously multiple promoter motifs and to define a DNA state that will
      facilitate transcription initiation. Here we propose a general model of promoter
      binding by TFIID, where co-activators, activators, and histone modifications
      promote and/or stabilize a conformational state of TFIID that results in core
      promoter engagement. Within this high affinity conformation, we propose that
      TFIID's extensive interaction with promoter DNA leads to topological changes in
      the DNA that facilitate the eventual loading of RNAP II. While more work is
      required to dissect the individual contributions of activators and repressors to
      TFIID's DNA binding, the recent cryo-EM studies provide a physical framework to
      guide future structural, biophysical, and biochemical experiments. 

PMID- 23863785
TI  - Urinary prostasin excretion is associated with adiposity in nonhypertensive
      African-American adolescents.
AB  - BACKGROUND: Metabolic abnormalities in obesity can overstimulate the renal
      epithelial sodium channel (ENaC) and subsequently lead to blood pressure (BP)
      elevation. Prostasin, a membrane-bound/secretive serine protease, is thought to
      activate ENaC via the proteolytic cleavage of the channel. Our specific aim was
      to explore whether there is a relationship between adiposity and urinary
      prostasin excretion at the population level. METHODS: In 271 African-American
      adolescents, urinary prostasin concentrations were determined by enzyme-linked
      immunosorbent assay and normalized by urinary creatinine. RESULTS: Urinary
      prostasin excretion increased in the overweight/obese group (n = 110, 38.2 +/-
      4.0 ng/mg) vs. the normal-weight group (n = 161, 20.7 +/- 1.2 ng/mg, P = 0.03).
      Urinary prostasin excretion was significantly correlated with BMI percentiles (r
      = 0.14, P = 0.02), waist circumference (r = 0.13, P = 0.05), total body fat mass
      (r = 0.20, P < 0.01), and percentage body fat (r = 0.23, P < 0.01). Urinary
      prostasin excretion was also correlated with plasma aldosterone (r = 0.11, P =
      0.05) and systolic BP (SBP; r = 0.15, P = 0.02), but the significances
      disappeared after adjustment of any of the adiposity variables. CONCLUSION: Our
      data for the first time suggest that adiposity plays a role in urinary prostasin
      excretion, and its associations with aldosterone and BP appear to be modulated by
      adiposity. Whether urinary prostasin excretion is a biomarker/mechanism
      underlying obesity-related hypertension deserves further investigations.

PMID- 23863786
TI  - [Anticoagulant therapy in comprehensive treatment of acute thrombosis of lower
      limb deep veins].
AB  - The authors analysed the findings of examination and treatment of 61 patients
      presenting with acute thrombophlebitis of lower-limb deep veins, also
      investigating the risk factors for the development of acute thrombophlebitis. Of
      these, 54 (88.5%) patients were found to have various risk factors. During
      treatment we studied efficacy of anticoagulant therapy, also carried out
      examination of the blood coagulogram. Depending on the method of anticoagulant
      therapy, all patients were subdivided into two groups: Group One patients (n=30)
      received a combination of heparin and warfarin and Group Two patients were given
      monotherapy with heparin alone. It was determined that combined administration of
      two anticoagulants resulted in prolongation of the value of the activated partial
      thromboplastin time by 20% from the normal one in the majority of those receiving
      it (n=22, 73.3%), whereas in Group Two patients it was observed only in 12
      (38.7%) patients. The values of the international normalized ratio in Group One
      patients were within the therapeutic (2.0-3.0) range, while in Group Two patients
      they were less than 2.0. There were neither haemorrhagic nor thrombolytic
      complications associated with administration of anticoagulants in either group. A
      combination of two anticoagulants turned out to be more effective for reaching
      adequate and safe hypocoagulation. The authors also worked out a therapeutic
      regimen and policy of follow up of patients presenting with acute
      thrombophlebitis. The comprehensive set of treatment included an effective route
      of paransal administration of the therapeutic mixture, favourably influencing the
      course and regress of the inflammatory process. The immediate results were as
      follows: good and satisfactory outcomes amounted to 93.4%, and poor results were
      noted in 6.6%. The short-term results were studied for up to 6 months revealing
      that 83% of patients had evidence of recanalization of the thrombosed veins, and
      only 17% demonstrated chronic occlusion. 

PMID- 23863787
TI  - [Administration of the generic prostaglandin E1 VAP 20(r) in patients with lower
      limb critical ischaemia: a prospective study].
AB  - OBJECTIVE: The study was aimed at assessing efficacy and safety of administering
      the generic alprostadil VAP in patients presenting with lower limb critical
      ischaemia. MATERIAL AND METHODS: We carried out a prospective study including a
      total of 30 patients with lower limb critical ischaemia. The patients' mean age
      was 67.7+/-7.8 years, with men predominating - 60%. Trophic ulcers were observed
      in 40% of patients. The proximal level of the lesion was localized in the
      arteries below the inguinal ligament in 19 (63.3%) patients, in the aortofemoral
      segment - in 9 (30%) patients, and in the popliteal-crural-plantar segment - in 2
      (6.6%) subjects. The average ankle-brachial index amounted to 0.49+/-0.4. The
      studied agent was used at a dose of 40 mcg once a day in patients with stage III
      ischaemia and a dose of 40 mcg twice daily in patients with stage IV ischaemia.
      The drug was administered for 14 days followed by a 14-day follow-up period.
      RESULTS: The pain syndrome score over the 14 days of treatment decreased twofold
      from 6.1+/-2.5 to 3.5+/-2.6 and within the subsequent 14 days it did not increase
      - 2.4+/-3.1 (p< 0.05). The number of patients in whom the pain syndrome decreased
      by 50% amounted to 19 (63.3%). The consumption of analgesic agents decreased from
      60% (at the beginning of treatment) to 12 (40%) (14 days after treatment) and to
      8 (26.6%) (at the end of the follow-up period). In patients with trophic ulcers,
      the average size of the ulcers during treatment decreased from 3.3+/-3.7 cm to
      2.8+/-3.8 after 14 days, and at the end of the follow-up period the size of the
      ulcers amounted to 2.1+/-2.8 cm (p >0.05). The number of patients responding to
      treatment amounted to 22 (77.3%). The ABI during treatment did not change, being
      0.49 +/- 0.4 at the beginning of treatment, 0.53+/-0.4 after 14 days of
      treatment, and 0.47+/-0.3 at the end of the follow-up period. There were no
      amputations either during treatment or within the follow-up period. Only one
      lethal outcome occurred which was related to acute coronary insufficiency. The
      "response to treatment" was significantly influenced only by the level of the
      proximal lesion and age (p<0.05). CONCLUSION: VAP 20(r) demonstrated good
      efficacy and tolerability comparable to those of the original preparations.

PMID- 23863788
TI  - [Mechanisms of antioedemic effect of bioflavonoids in experiment].
AB  - In treatment of various-aetiology chronic oedemas, of great importance is a
      possibility of exerting an influence on the resorptional, transportation and
      transmission functions of the lymphatic system, as well as on the
      microcirculatory blood channel, because they all maintain the balance of fluid
      exchange in tissues. There exist various causes of chronic oedema, which requires
      a differentiated approach to administration of bioflavonoids possessing different
      mechanisms of antioedemic action. With this in mind we carried out experimental
      histomorphometric studies on 24 rats, aimed at determining variously directed
      effects of agents belonging to the class of bioflavonoids - phlebodia 600
      (diosmin) and troxerutin on regeneration ability of the lymphatic endothelium and
      permeability of blood capillaries. It was determined that phlebodia 600 exerts a
      direct influence upon the functional state of the lymphatic system, activating
      proliferation of the lymphatic endothelium by means of gemmation, which leads to
      the formation of new capillary lymphatic networks with the resulting increase in
      both the total absorption area of the lymphatic capillary networks and the volume
      of lymph reabsorption. Troxerutin acts predominantly on the endothelium of blood
      capillaries, decreasing permeability in the arterial segment of the capillary,
      thus lowering the total volume of fluid in the interstitial space and accordingly
      the load on the lymphatic system. 

PMID- 23863789
TI  - [Intraoperative assessment of composite bypass grafts by means of ultrasonic
      Doppler flowmetry].
AB  - The use of the both internal thoracic arteries while forming a composite bypass
      graft has been suggested as a method making it possible to carry out total
      myocardial revascularization. However, controversial still remain the problem of
      the distribution of blood in these bypass grafts, as well as that concerning T
      grafts' capability of providing the sufficient blood inflow to the basin of the
      coronary arteries being bypassed. The method of ultrasonic Doppler flowmetry was
      used to perform the intraoperative assessment of 59 composite bypass grafts along
      such parameters as the pulsatility index (PI), mean volume blood flow velocity
      (Qmean), and percentage of diastolic volumetric filling (DF). The obtained
      findings were statistically processed making it possible to obtain the average
      parameters of blood flow for the composite bypass grafts and their branches. A
      dependence was established between blood flow distribution in the composite
      conduit and the degree of the lesion of the artery being bypassed. 

PMID- 23863790
TI  - [Experience with hybrid techniques of surgical treatment of patients with lower
      limb critical ischaemia].
AB  - The authors present their original experience with the use of hybrid techniques
      of surgical treatment in a total of 19 patients with lower limb critical
      ischaemia (LLCI) on the background of complex lesions of the arteries of lower
      extremities. They describe various types of hybrid techniques of surgical
      treatment of patients with critical ischaemia on the background of chronic
      obliterating diseases of lower-limb arteries. Also discussed are 3 varieties of
      clinical situations in which it is appropriate to employ the hybrid method:
      thrombosis of the bypass graft, multi-storey lesions of lower-limb arteries, and
      the use of a hybrid technique in order to decrease the size of the surgical
      wound. The period of follow up varied from 2 to 36 months. The limbs were saved
      in all the patients during the whole follow-up period. Two patients were found to
      have thrombosis of the reconstructed segment after 1.5-5 months. 

PMID- 23863791
TI  - [Hybrid operation in combined pathology].
AB  - Presented herein are the results of successful surgical treatment for a combined
      atherosclerotic lesion of arteries of the coronary and carotid basin in a patient
      with coronary artery disease. 

PMID- 23863792
TI  - [Russian observational programme SPEKTR: analysis of age-specific structure of
      patients with chronic venous diseases].
AB  - The authors studied the age-related structure of 864 patients with chronic venous
      diseases (CVD) by means of analysing the database of the Russian Programme SPEKTR
      (2011-2012). Most often special medical care was sought by persons of able-bodied
      age (31-60 years): men - 60.6%, women - 63.8%. Class C1 in women was registered
      at the age under 20 years in 49.5% of cases, in elder groups - from 66.4% to
      76.1%. In men, it was registered 1.3-2-8 times less often in all age groups.
      Class C2 amounted to 75% of cases in women under 20 years; then 50% (21-30
      years), increasing to 79.6% (61-70 years). Class C2 in men under 20 years was
      observed in 100%, then the proportion fluctuated within the bounds of 80%
      irrespective of the age. The maximum of registering C3 fell to the age of 41-50
      years (women - 48%, men - 53.2%). The number of severe forms (C4-C6) in men was
      considerably more: 31-40 years - 20.2% versus 4.7% in women; 41-50 years - 59.6%
      versus 17.3%; 51-60 years - 46.7% versus 29.4%. Trophic ulcers were revealed in
      men most often at the age of 31 - 60 years - 22% in women in the analogous group 
      4.9%. The anamnesis of CVD increased with age. Adequate treatment for CVD in all
      age groups prior to the visit to the phleblogist had been carried out very
      rarely. 

PMID- 23863793
TI  - [Radiofrequency obliteration of veins in surgical treatment of varicose disease].
AB  - OBJECTIVES: 1) To show the role and place of endovenous radiofrequency
      obliteration (RFO) in removing the vertical reflux in the varicose major
      superficial large-diameter veins. 2) To assess the outcomes of treatment of
      patients with varicose disease and to determine their correlation with the scales
      VCSS, VSDS and CEAP. MATERIAL AND METHODS: Endovascular methods, the technique of
      endovascular radiofrequency (RFO) ClosureFAST belongs to, are intended to within
      the shortest terms remove reflux without disturbing the patient's habitual way of
      life and along with it to improve the main aspects of quality of life.From 2009
      to 2011, we operated on 110 patients (a total of 135 extremities). The mean age
      amounted to 41 years. Patients with an ostium-adjacent venous diameter of less
      than 1.3 cm were excluded from the sample, 37% of patients had various trophic
      impairments, 41% of patients had various concomitant somatic pathology, and 17%
      of patients had the body weight index (BWI) exceeding 30. Diagnosis and severity
      of the disease were formed with due regard for the scales of disease severity
      VCSS, VSDS and CEAP, as well as the worked out diagnostic algorithm. The venous
      status was evaluated by the findings of the objective examination and triplex
      angioscanning. The groups of patients with reflux along the altered venous
      segments were distributed as follows: 32.6% of patients - the superior vena cava
      with the classical course, 8% - the inferior vena cava, 7% - vein of Giacomini,
      16% - the anterior accessory vein, 8% - the anterior lateral inflow, 28.4% - the
      extrafascial course of the vessel. The pain factor according to the analogue
      scale amounted to 0.8. In the postoperative period, the patients were followed up
      and examined on day 3, day 10 and then after 1, 3, 6, 12 months and more.
      RESULTS: RFO was successfully used in patients in all venous basins irrespective
      of the diameter and anatomical course of the venous structures. In 98% of cases
      we managed to achieve occlusion with the removal of the reflux within the terms
      of up to one year. Regress of clinical symptoms and improvement of quality of
      life were reflected in the VCSS. 100% of patients returned to the habitual
      activity on the day of operation. CONCLUSION: RFO with obvious efficacy may be
      used in various topographical areas of lower limbs regardless of the veins'
      diameter and their anatomical course. RFO is a method of choice in patients with
      high BMI and accompanying somatic pathology. Ambulatory follow up of patients
      with severe somatic pathology is possible, independently of decompensation of
      venous pathology. Clinical scales of the disease severity VCSS and VSDS are
      convenient in use, clearly reflecting the dynamics of the disease in the pre- and
      postoperative periods, which makes it possible to recommend them for wide
      application along with other scales on studying quality of life.

PMID- 23863794
TI  - [Haemodynamic and clinical efficacy of electric muscular stimulation of the
      venous outflow in prevention of postoperative venous thromboembolic
      complications].
AB  - The present clinical and experimental study was carried out in order to evaluate
      efficacy of electrical stimulation of the crural muscles with the purpose of
      preventing postoperative venous thromboembolic complications. At the first stage
      by means of ultrasonographic angioscanning in apparently healthy volunteers
      (n=21) we evaluated the linear velocity of blood flow on the popliteal vein on
      the background of using myostimulation and compression bandage with various
      levels of pressure applied either separately or in a combination with each other.
      It was revealed that electrical stimulation of the crural muscles led to a 2.8
      4.5-fold increase in the peck velocity of blood flow, while the compression
      decreased the parameters of the venous outflow both at rest and during muscular
      contraction. By means of theoretical calculations it was determined that an
      optimal compression profile for a combination with electrical stimulation is a
      pressure under the bandage equalling 20-40 mm Hg, providing substantial
      acceleration of the venous outflow with the laminary blood flow preserved. At the
      second stage we assessed efficacy of comprehensive prevention of venous
      thromboembolism with the use of electromyostimulation, the respective compression
      bandage and direct anticoagulants in surgical-profile patients from a high-risk
      group (n=90) by means of ultrasound screening of the venous system during the
      whole postoperative period. When myostimulation was used in the regimen of 3-5
      procedures a day, the frequency of venous thrombosis amounted to 40% (n=10) and
      did not significantly differ from that in patients not subjected to
      myostimulation (25%, n=40). When myostimulation was used in the regimen of 5-10
      procedures per day, the frequency of venous thrombosis turned out to be
      considerably lower (2.5%, n=40). A conclusion was made on efficacy of using this
      method in the examined group of patients. 

PMID- 23863795
TI  - Immediate and remote results of using carotid endarterectomy and stenting of
      internal carotid arteries.
AB  - OBJECTIVE: The study was aimed at analysing the outcomes of single-centre
      carefully selected use of the methods of carotid stenting and endarterectomy in
      patients with atherosclerotic lesions of the cervical segment of the internal
      carotid artery (ICA) in the immediate and remote postoperative periods. MATERIAL
      AND METHODS: We retsospectively analysed the data regarding a total of 340
      patients presenting with atherosclerotic lesions of the internal carotid artery
      over the period from 2007 to 2011. Depending on the method of revascularization,
      all patients were subdivided into two groups: the group undergoing stenting of
      the internal carotid artery (a total of 170 patients) and the group of carotid
      endarterectomy (170 patients). The group of stenting included significantly more
      patients with a history of myocardial infarction (31.8% versus 5.3% (p < 0.001),
      functional class III-IV chronic cardiac insufficiency (17.6% vs 1.2%, p = 0.006),
      and chronic obstructive pulmonary disease (12.4% vs 3.5%; p = 0.004). The first
      also had more patients with previously endured ischaemic stroke in the basin of
      the ipsilateral ICA (21.8% vs 12.4%; p = 0.03). However, the both groups were
      comparable by the number of symptomatic (65.3% and 59.4%. p = 0.314) and
      asymptomatic (34.7% and 40.6%; p = 0.314) lesions of the ICA. Prior to operative
      intervention 95.3% of patients were subjected to coronarography and selective
      angiography of the brachiocephalic arteries (DCA). Stenting of the ICA was
      carried out under local anaesthesia in 100% of cases. Protection of the brain
      from embolism was used in all cases of stenting, of theses 103 patients (60.6%)
      patients received the system of proximal protection MoMa Ultra. Carotid
      endarterectomy was carried out under general anaesthesia in all patients. A
      temporary bypass was employed in 36.5% of cases. A patch was sewn into the
      arteriotomic orifice in 85.9% of cases. The outcomes of carotid revascularization
      were assessed in both the immediate and remote postoperative periods. RESULTS: No
      statistically significant differences by such end points as death, stroke,
      myocardial infarction, as well as by the composite parameter (death, stroke,
      infarction) and the number of local complications between the two methods of
      revascularization in the immediate (up to 30 days) postoperative period were
      observed. There were two lethal outcomes occurring in the group of carotid
      endarterectomy due to acute myocardial infarction and major ipsilateral stroke.
      The groups significantly differed by the frequency of damage to the
      craniocerebral nerves (0% in the carotid stenting group versus 4.1% in the CEA
      group; p = 0.015). In the remote postoperative period averagely amounting to 16.4
      +/- 9.5 months, no lethal outcomes in either group were registered, with the
      groups also not differing by the rate of either strokes, infractions, or
      restenoses/occlusions of the ICA. CONCLUSION: Carefully selected use of CEA and
      carotid stenting at one medical facility makes it possible to obtain comparably
      low indices of "death, infarction, stroke" in the immediate postoperative period,
      which are substantially lower than those reported in large randomized studies
      [1.2% versus 5.2% (CREST) in stenting, 2.9% vs 4.5% (CREST) in CEA], to
      considerably decrease the total rate of mortality, stroke, infarction in the
      immediate postoperative period (2.1% for all patients in the study, and 3.0% for
      symptomatic patients versus 3.3% for the measure "death, stroke" in the NACET
      study), to obtain comparably low rates of death, infarction or stroke in the
      remote postoperative period, to enlarge the possibilities of carotid
      revascularization in the presence of limiting factors of each of the techniques.

PMID- 23863796
TI  - [Results of splenorenal venous bypass grafting in patients with hepatocirrhosis].
AB  - Presented herein are the results of surgical treatment of 79 patients with
      intrahepatic portal hypertension who underwent splenorenal venous bypass grafting
      after splenectomy. The patients' age varied from 8 to 64 years, averaging 37.3
      years. The authors followed up the immediate and remote results of treatment at
      terms varying from 1 to 20 years. Of the early postoperative complications
      mention should be made that intra-abdominal haemorrhage was revealed in 4 (5%)
      patients, six (7.6%) patients were found to develop left-side reactive pleuritis,
      one patient (1.2%) - bilateral pleuritis and pericarditis, subcutaneous
      eventration was revealed in 1 patient with pronounced ascites (1.2%). Haemorrhage
      from varicose dilated oesophageal veins in the early postoperative period was
      observed in 8 (10%) cases. Posthaemorrhagic anaemia was present in 27 cases
      (43.1%). The mortality rate in the early postoperative period amounted to 5% (4).
      We followed up the long-term results in 51 (64.5%) of the 79 patients at terms up
      to 5 years after surgery, in 17 patients at terms up to 10 years following
      interventions, in 9 at terms up to 15 years, and in one patient up to 20 years. A
      total of 3 patients died within the first postoperative year. 48 (94%) patients
      are alive 5 years after the operation, 10 - after ten years, with 7 having died.
      Five patients are still alive more than 15 years, four died, one followed up
      woman is still alive after 20 years with a satisfactory result. 

PMID- 23863797
TI  - Angioplasty and stenting of renal arteries: in search for prognostic criteria.
AB  - OBJECTIVE: transcutaneous angioplasty with stenting of renal arteries has for a
      long time been considered the generally accepted technique of treatment for
      atherosclerotic stenosis of renal arteries. Publications concerning the results
      of recent studies (ASIRAL, DRATIC, STAR) call into doubt the value of this
      method. However, these studies have been criticized for their methodological
      shortcomings. In our work we attempted to reveal the interrelationship between
      the clinical and radiological parameters of patients presenting with
      atherosclerotic narrowing of renal arteries and the results of transcutaneous
      angioplasty with stenting. PATIENTS AND METHODS: We carried out a retrospective
      study based on analyzing the case histories of all patients having endured
      transcutaneous angioplasty with stenting of renal arteries at the Vascular
      Surgery Department of the "Soroka" Medical Centre (Beer Sheva, Israel) over the
      period from 2000 to 2007. The criteria for inclusion of patients into the study
      group were as follows: 1) diagnosis of atherosclerotic stenosis of renal arteries
      based on the Doppler ultrasound scan; 2) treatment using transcutaneous
      angioplasty with stenting of renal arteries; 3) dispensary follow up during 18
      months after the procedure. The patients with atherosclerotic stenosis of renal
      arteries or those unavailable for follow up were excluded from the study. All
      available clinical radiological data were grouped into tables and subjected to
      statistical analysis (SPSS, Student's t-test, the ANOVA, and chi-squared test).
      The findings regarding arterial pressure and the level of blood creatinine were
      registered at terms equalling 1, 6, 12, and 18 months after the procedure.
      RESULTS: A total of forty one patients were included into the final statistical
      analysis; the patients' average age amounted to 67.6+/-8.7 years and 70.7% were
      male patients. We observed a considerable decrease in the average indices of
      arterial pressure one month after the procedure (systolic pressure dropped from
      160+/-24.7 to 141.8+/-23.6 mm Hg and diastolic pressure fell from 83+/-12.9 to
      58.8+/-11.8 mm Hg; p< 0.001). The decrease in arterial pressure maintained during
      the whole follow-up period. After 18 months the mean indices of systolic pressure
      amounted to 135.0+/-35.1 mm Hg, with those of diastolic pressure equalling 71.3+/
      16.5 mm Hg, p>0.001). The renal function (blood serum creatinine level) remained
      stable during the whole period of low up. CONCLUSION: The obtained findings
      demonstrated that successful transcutaneous angioplasty with stenting of
      atherosclerotic stenosis of renal arteries helps control arterial hypertension.
      No direct positive effect of this procedure on the renal function was revealed.
      In our opinion, the main problem in selecting the patients this intervention is
      indicated for consists in not knowing the criteria correlating with successful
      outcomes, therefore further studies should be aimed at revealing these criteria.

PMID- 23863798
TI  - Current state of affairs in the treatment of infrainguinal critical limb
      ischemia.
AB  - Atherosclerosis is widespread in Western society and is the leading cause of
      morbidity and mortality in the United States (US). Epidemiological studies
      indicate that peripheral artery disease (PAD) has a prevalence of 3-10% in the
      general population. This rate increases to 15-20% in persons over 70 years of
      age, and PAD is particularly common in individuals who smoke or have diabetes.
      Further highlighting the lack of current treatment uniformity, the Society for
      Vascular Surgery has recently designated the goal of clarifying optimal treatment
      for CLI as one of its top societal priorities. 

PMID- 23863799
TI  - [Surgical treatment of an aneurysm of the deep femoral artery].
AB  - We report herein a rare clinical case concerning an isolated deep aneurysm of the
      femoral artery with extravasal compression of the superficial femoral vein,
      complicated by venous insufficiency and oedema of the lower extremity. A 66-year
      old female patient was admitted complaining of a pulsing formation on the left
      inguinal region, a feeling of puffiness and heaviness of the left lower
      extremity. The findings of the ultrasonographic Doppler scanning showed no signs
      of deep veins thrombosis, however, in the projection of the Skarpovsky's triangle
      of the left lower limb, there was an aneurysmatic dilatation of the deep femoral
      artery, arteriovenous malformation (?). In order to specify the diagnosis, we
      performed multispiral CT angiography revealing an isolated aneurysm of the deep
      femoral artery. Therefore, we carried out successful resection of the aneurysm
      with the end-to-side reimplantation of the unaltered distal portion of the deep
      femoral artery into the superficial femoral artery. Preoperative multispiral CT
      angiography is a valuable non-invasive diagnostic tool serving to evaluate not
      only an aneurysm itself but the distal arterial bed. 

PMID- 23863800
TI  - [Thromboembolism of the palmar arch and digital arteries on the background of
      posttraumatic aneurysm of the left brachial artery].
AB  - The present article is aimed at describing a clinical case report associated with
      thromboembolism of the distal arterial bed of the left upper extremity (the
      palmar arches of the hand and interdigital arteries) with the development of
      severe acute ischaemia on the background of a false post-traumatic aneurysm of
      the left brachial artery. The patient underwent comprehensive treatment including
      conservative therapy and stagewise operative interventions. As one of the
      components of conservative therapy was systemic thrombolysis of Actilyse. The
      first stage of the operative intervention consisted in upper thoracic endoscopic
      sympathectomy on the left with positive dynamics of the state of soft tissue of
      the left hand. The second stage was resection of the pseudoaneurysm of the left
      brachial artery and amputation of the phalanges II-V of the fingers of the left
      hand. The mentioned approach made it possible to save the left hand and preserve
      its grasping function. 

PMID- 23863801
TI  - Visit-to-visit blood pressure variability is related to albuminuria variability
      and progression in patients with type 2 diabetes.
AB  - Recent studies have suggested that visit-to-visit variability of blood pressure
      (BP) is correlated with microalbuminuria in patients with diabetes, independent
      of mean pressure. We investigated the contribution of BP variability to
      albuminuria progression in normoalbuminuric type 2 diabetes patients. BP and
      urinary albumin excretion of patients were assessed in each visit during a median
      follow-up of 31 months. Variability was assessed using standard deviation,
      coefficient of variation, standard deviation independent of mean, peak, average
      real variability, and average real variability independent of mean. Of 194
      patients enrolled, 31 subjects (16.0%) developed microalbuminuria. Systolic blood
      pressure (SBP) variability indices (except for coefficient of variation and
      average real variability) were significant predictors of microalbuminuria in
      multivariate Cox regression models (hazard ratio ranging from 2.02 to 2.76). The
      same was not observed for diastolic blood pressure. Using linear regression, SBP
      variability significantly correlated with some but not all indices of albuminuria
      variability. Peak SBP was the strongest predictor of albuminuria variability in
      multivariate models (standardized beta ranging from 0.216 to 0.339). In
      conclusion, visit-to-visit variability of SBP is an independent risk factor for
      development of microalbuminuria in patients with diabetes, and is associated with
      an increased variability in albuminuria.

PMID- 23863802
TI  - CYP3A5 polymorphism, amlodipine and hypertension.
AB  - As a major cardiovascular risk factor for stroke, coronary artery disease, heart
      failure and end-stage renal disease, hypertension affects approximately one
      billion people and causes large economic burden worldwide. Cytochrome P450 3A5
      (CYP3A5), belonging to the CYP3A subfamily, has been implicated in the regulation
      of blood pressure and may serve as a potential risk factor for the development of
      hypertension. Increased CYP3A5 activity could cause sodium and water retention by
      affecting the metabolism of cortisol in the kidneys. Furthermore, polymorphic
      CYP3A5 genotypes have been shown to cause differences in blood pressure response
      to antihypertensive drugs. Several studies have investigated the role of CYP3A5
      in blood pressure response to amlodipine. However, recent data on the role of
      CYP3A5 in hypertension development and treatment are inconsistent. This review
      summarizes what is known regarding the relationship of CYP3A5 with hypertension,
      discusses the limitations in present studies, highlights the gaps and directs
      research to this field. 

PMID- 23863803
TI  - Pulse wave analysis for the prediction of preeclampsia.
AB  - Preeclampsia is associated with a number of changes to maternal vascular
      function. Assessment of arterial stiffness using pulse wave analysis (PWA) has
      been proposed as a means of predicting preeclampsia before the onset of
      clinically detectable disease. One hundred and eighty women with ?2 risk factors
      for preeclampsia were examined at gestational weeks 16 and 28, of whom 17 (9.4%)
      developed preeclampsia. To study the effects of pregnancy itself women were also
      examined at 6-9 months post-natally; an additional 30 healthy non-pregnant women
      were also examined. PWA was performed using SphygmoCor; augmentation index (AIx),
      a marker of arterial wave reflection, was also measured using EndoPAT-2000. Women
      who developed preeclampsia were more likely to be overweight and had a higher
      brachial and central diastolic BP at gestational week 16 than those who remained
      normotensive. There was no difference in any parameter of arterial wave
      reflection between non-pregnant and pregnant women, nor between those who
      developed preeclampsia and those who remained normotensive, when examined at
      weeks 16 and 28 or post-natally. In this cohort of women with risk factors for
      preeclampsia, PWA did not provide additional information beyond brachial blood
      pressure and maternal risk factor profile about the risk of future development of
      preeclampsia. 

PMID- 23863804
TI  - Spironolactone increases serum uric acid levels in patients with chronic kidney
      disease.

PMID- 23863805
TI  - Effect of the angiotensin II receptor antagonist olmesartan on morning home blood
      pressure in hypertension: HONEST study at 16 weeks.
AB  - Morning home blood pressure (BP) levels are more closely associated with
      cardiovascular risk than clinic BP levels. However, control of morning home BP
      has been worse than that of clinic BP in clinical practice. We examined the
      effects of olmesartan-based treatment using data (n=21 341) from the first 16
      weeks of the Home BP measurement with Olmesartan Naive patients to Establish
      Standard Target blood pressure (HONEST) study, a prospective observational study
      for olmesartan-naive patients with essential hypertension. After 16-week
      olmesartan-based treatment, the clinic and morning home systolic BP (SBP) lowered
      from 151.6+/-16.4 and 153.6+/-19.0 mm Hg to 135.0+/-13.7 and 135.5+/-13.7 mm Hg,
      respectively (P<0.0001). The achievement percentage of target morning home SBP
      (<135 mm Hg) in all patients, those with diabetes mellitus (DM), and those with
      chronic kidney disease (CKD) increased from 13.5, 16.4 and 17.2% to 50.8, 47.9
      and 48.8%, respectively, and the proportion of patients with well-controlled
      hypertension (clinic SBP<140 mm Hg and morning home SBP<135 mm Hg) increased from
      7.9, 9.2 and 10.2% to 38.9, 34.5 and 36.3%, respectively. After 16-week
      olmesartan-based treatment, the proportion of patients with masked and white coat
      hypertension changed from 11.8 to 24.2% and 5.6 to 11.9%. In conclusion, both
      clinic and morning home BP in all, DM and CKD patients improved with 16-week
      olmesartan-based treatment in the 'real world', and the results showed a
      sustained 24-hour BP-lowering effect of olmesartan. Decrease in clinic and home
      BP resulted in an increased rate of masked and white coat hypertension, and
      further management is needed in those patients. 

PMID- 23863806
TI  - Dry plasma synthesis of a MWNT-Pt nanohybrid as an efficient and low-cost counter
      electrode material for dye-sensitized solar cells.
AB  - Dry plasma reduction (DPR) is an excellent approach for easily and uniformly
      immobilizing many platinum nanoparticles (Pt-NPs) with a size of 2-3 nm on both
      inner and outer surfaces of MWNTs under atmospheric pressure and at near room
      temperature. The MWNT-Pt nanohybrid exhibits quite low charge transfer resistance
      for dye-sensitized solar cells. 

PMID- 23863808
TI  - Fast GCaMPs for improved tracking of neuronal activity.
AB  - The use of genetically encodable calcium indicator proteins to monitor neuronal
      activity is hampered by slow response times and a narrow Ca(2+)-sensitive range.
      Here we identify three performance-limiting features of GCaMP3, a popular
      genetically encodable calcium indicator protein. First, we find that affinity is
      regulated by the calmodulin domain's Ca(2+)-chelating residues. Second, we find
      that off-responses to Ca(2+) are rate-limited by dissociation of the RS20 domain
      from calmodulin's hydrophobic pocket. Third, we find that on-responses are
      limited by fast binding to the N-lobe at high Ca(2+) and by slow binding to the C
      lobe at lower Ca(2+). We develop Fast-GCaMPs, which have up to 20-fold
      accelerated off-responses and show that they have a 200-fold range of K(D),
      allowing coexpression of multiple variants to span an expanded range of Ca(2+)
      concentrations. Finally, we show that Fast-GCaMPs track natural song in
      Drosophila auditory neurons and generate rapid responses in mammalian neurons,
      supporting the utility of our approach.

PMID- 23863809
TI  - A symptom-limited incremental step test determines maximum physiological
      responses in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Step tests have been used to evaluate exercise tolerance and effort
      related hypoxemia in different diseases. A symptom-limited incremental step test
      (IST) has never been tested in COPD patients. AIM: To compare maximal
      physiological responses between an IST and cardiopulmonary exercise testing
      (CPET), to test the reproducibility of the IST on different days, and to provide
      a predict equation to estimate VO2 from the IST in patients with COPD. MATERIAL
      AND METHODS: At the same day, thirty-four patients (VEF1 46 +/- 14% of pred)
      underwent a CPET on cycle ergometer and the first IST (IST-1) (1 h apart). After
      2-5 days, patients repeated the IST (IST-2). Pulmonary gas exchange was measured
      during all tests. RESULTS: Peak VO2 was significantly higher in IST-1 and IST-2
      than in CEPT (Mean +/- SD: 1.19 +/- 0.39 L, 1.20 +/- 0.40 L, 1.07 +/- 0.35 L)
      with no difference for ventilation (VE), heart rate (HR), and perception of
      effort. ISTs were highly reproducible, with significant intraclass correlation
      coefficient (CCI [95% confidence interval]) for number of steps (0.98[0.95
      0.99]), VO2 (0.99 [0.98-0.99]), VE (0.97[0.93-0.99]), HR (0.92[0.81-0.97]), and
      SpO2 (0.96[0.90-0.98]). Desaturation was significantly higher for IST-1 and IST-2
      compared with cycling (Mean +/- SD: -6 +/- 5%, -6 +/- 4%, -3 +/- 3%). Number of
      steps and patient weight explained 81% of the variance in peak VO2 (p < 0.001).
      CONCLUSION: A symptom-limited incremental step test, externally paced, elicits
      maximal cardiopulmonary and metabolic responses, and is well tolerated and
      reproducible in patients with COPD.

PMID- 23863810
TI  - Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates.
AB  - We examined the metabolic characteristics that attend the development of type 2
      diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated
      in the ACT NOW Study and had complete end-of-study metabolic measurements.
      Subjects were randomized to receive pioglitazone (PGZ; 45 mg/day) or placebo and
      were observed for a median of 2.4 years. Indices of insulin sensitivity (Matsuda
      index [MI]), insulin secretion (IS)/insulin resistance (IR; DeltaI0-120/DeltaG0
      120, DeltaIS rate [ISR]0-120/DeltaG0-120), and beta-cell function (DeltaI/DeltaG
      * MI and DeltaISR/DeltaG * MI) were calculated from plasma glucose, insulin, and
      C-peptide concentrations during oral glucose tolerance tests at baseline and
      study end. Diabetes developed in 45 placebo-treated vs. 15 PGZ-treated subjects
      (odds ratio [OR] 0.28 [95% CI 0.15-0.49]; P < 0.0001); 48% of PGZ-treated
      subjects reverted to normal glucose tolerance (NGT) versus 28% of placebo-treated
      subjects (P < 0.005). Higher final glucose tolerance status (NGT > IGT > T2DM)
      was associated with improvements in insulin sensitivity (OR 0.61 [95% CI 0.54
      0.80]), IS (OR 0.61 [95% CI 0.50-0.75]), and beta-cell function (ln IS/IR index
      and ln ISR/IR index) (OR 0.26 [95% CI 0.19-0.37]; all P < 0.0001). Of the factors
      measured, improved beta-cell function was most closely associated with final
      glucose tolerance status. 

PMID- 23863811
TI  - Loss of prohibitin induces mitochondrial damages altering beta-cell function and
      survival and is responsible for gradual diabetes development.
AB  - Prohibitins are highly conserved proteins mainly implicated in the maintenance of
      mitochondrial function and architecture. Their dysfunctions are associated with
      aging, cancer, obesity, and inflammation. However, their possible role in
      pancreatic beta-cells remains unknown. The current study documents the expression
      of prohibitins in human and rodent islets and their key role for beta-cell
      function and survival. Ablation of Phb2 in mouse beta-cells sequentially resulted
      in impairment of mitochondrial function and insulin secretion, loss of beta
      cells, progressive alteration of glucose homeostasis, and, ultimately, severe
      diabetes. Remarkably, these events progressed over a 3-week period of time after
      weaning. Defective insulin supply in beta-Phb2(-/-) mice was contributed by both
      beta-cell dysfunction and apoptosis, temporarily compensated by increased beta
      cell proliferation. At the molecular level, we observed that deletion of Phb2
      caused mitochondrial abnormalities, including reduction of mitochondrial DNA copy
      number and respiratory chain complex IV levels, altered mitochondrial activity,
      cleavage of L-optic atrophy 1, and mitochondrial fragmentation. Overall, our data
      demonstrate that Phb2 is essential for metabolic activation of mitochondria and,
      as a consequence, for function and survival of beta-cells. 

PMID- 23863812
TI  - Combination pravastatin and valsartan treatment has additive beneficial effects
      to simultaneously improve both metabolic and cardiovascular phenotypes beyond
      that of monotherapy with either drug in patients with primary
      hypercholesterolemia.
AB  - Statin and angiotensin II type 1 receptor blocker therapy improves endothelial
      dysfunction using distinct mechanisms. We evaluated simultaneous vascular and
      metabolic responses to pravastatin and valsartan therapy, alone or in
      combination, in hypercholesterolemic patients. Forty-eight hypercholesterolemic
      patients (23 had metabolic syndrome) were given pravastatin 40 mg and placebo,
      pravastatin 40 mg and valsartan 160 mg, or valsartan 160 mg and placebo daily
      during each 2-month treatment period in a randomized, single-blind, placebo
      controlled, crossover trial with three treatment arms and two washout periods
      (each 2 months). Brachial artery flow-mediated dilation and C-reactive protein
      improved to a greater extent with combined therapy compared with either
      monotherapy. Importantly, we also observed simultaneous improvement in metabolic
      phenotypes, with all three treatments causing increased plasma adiponectin
      levels, reduced fasting insulin levels, and increased insulin sensitivity
      relative to baseline measurements. For the first time in a statin combination
      trial, pravastatin combined with valsartan therapy increased plasma adiponectin,
      lowered fasting insulin levels, and improved insulin sensitivity in an additive
      manner when compared with monotherapy alone. In contrast to other statins,
      hydrophilic pavastatin may be combined with other drugs to safely reach lipid
      target levels while simultaneously improving the metabolic and cardiovascular
      phenotype of patients at high risk. 

PMID- 23863813
TI  - Nitric oxide directly promotes vascular endothelial insulin transport.
AB  - Insulin resistance strongly associates with decreased nitric oxide (NO)
      bioavailability and endothelial dysfunction. In the vasculature, NO mediates
      multiple processes that affect insulin delivery, including dilating both
      resistance and terminal arterioles in skeletal muscle in vivo. However, whether
      NO directly regulates vascular endothelial cell (EC) insulin uptake and its
      transendothelial transport (TET) is unknown. We report in this article that L
      N(G)-nitro-L-arginine methyl ester (L-NAME) pretreatment blocked, whereas L
      arginine and sodium nitroprusside (SNP) each enhanced, EC uptake of fluorescein
      isothiocyanate (FITC)-labeled insulin. SNP also partly or fully reversed the
      inhibition of EC insulin uptake caused by L-NAME, wortmannin, the Src inhibitor
      PP1, and tumor necrosis factor-alpha. In addition, SNP promoted
      [(125)I]Tyr(A14)insulin TET by ~40%. Treatment with insulin with and without SNP
      did not affect EC cyclic guanosine monophosphate (cGMP) levels, and the cGMP
      analog 8-bromo-cGMP did not affect FITC-insulin uptake. In contrast, treatment
      with insulin and SNP significantly increased EC protein S-nitrosylation, the
      colocalization of S-nitrosothiol (S-NO) and protein-tyrosine phosphatase 1B
      (PTP1B), and Akt phosphorylation at Ser(473) and inhibited PTP1B activity.
      Moreover, a high-fat diet significantly inhibited EC insulin-stimulated Akt
      phosphorylation and FITC-insulin uptake that was partially reversed by SNP in
      rats. Finally, inhibition of S-nitrosylation by knockdown of thioredoxin
      interacting protein completely eliminated SNP-enhanced FITC-insulin uptake. We
      conclude that NO directly promotes EC insulin transport by enhancing protein S
      nitrosylation. NO also inhibits PTP1B activity, thereby enhancing insulin
      signaling.

PMID- 23863815
TI  - Psychometric evaluation of a modified version of the family satisfaction in the
      ICU survey in parents/caregivers of critically ill children*.
AB  - OBJECTIVES: The Family Satisfaction in the Intensive Care Unit 24 (FS-ICU 24)
      survey consists of two domains (overall care and medical decision-making) and was
      validated only for family members of adult patients in the ICU. The purpose of
      this study was to evaluate the internal consistency and construct validity of the
      FS-ICU 24 survey modified for parents/caregivers of pediatric patients (Pediatric
      Family Satisfaction in the Intensive Care Unit 24 [pFS-ICU 24]) by comparing it
      to McPherson's PICU satisfaction survey, in a similar racial/ethnic population as
      the original Family Satisfaction in the Intensive Care Unit validation studies
      (English-speaking Caucasian adults). We hypothesized that the pFS-ICU 24 would be
      psychometrically sound to assess satisfaction of parents/caregivers with
      critically ill children. DESIGN: A prospective survey examination of the pFS-ICU
      24 was performed (1/2011-12/2011). Participants completed the pFS-ICU 24 and
      McPherson's survey with the order of administration alternated with each
      consecutive participant to control for order effects (nonrandomized). Cronbach's
      alphas (alpha) were calculated to examine internal consistency reliability, and
      Pearson correlations were calculated to examine construct validity. SETTING:
      University-affiliated, children's hospital, cardiothoracic ICU. SUBJECTS: English
      speaking Caucasian parents/caregivers of children less than 18 years old admitted
      to the ICU (on hospital day 3 or 4) were approached to participate if they were
      at the bedside for greater than or equal to 2 days. MEASUREMENTS AND MAIN
      RESULTS: Fifty parents/caregivers completed the surveys (mean age +/- SD = 36.2+/
      9.6 yr; 56% mothers). The alpha for the pFS-ICU 24 was 0.95 and 0.92 for
      McPherson's survey. Overall, responses for the pFS-ICU 24 and McPherson's survey
      were significantly correlated (r = 0.73; p < 0.01). The average overall pFS-ICU
      24 satisfaction score was 92.6 +/- 8.3. The average pFS-ICU 24 satisfaction with
      care domain and medical decision-making domain scores were 93.3 +/- 8.8 and 91.2
      +/- 8.9, respectively. CONCLUSIONS: The pFS-ICU 24 is a psychometrically sound
      measure of satisfaction with care and medical decision-making of
      parents/caregivers with children in the ICU.

PMID- 23863816
TI  - Patient-ventilator asynchrony during noninvasive pressure support ventilation and
      neurally adjusted ventilatory assist in infants and children.
AB  - OBJECTIVES: To document the prevalence of asynchrony events during noninvasive
      ventilation in pressure support in infants and in children and to compare the
      results with neurally adjusted ventilatory assist. DESIGN: Prospective randomized
      cross-over study in children undergoing noninvasive ventilation. SETTING: The
      study was performed in a PICU. PATIENTS: From 4 weeks to 5 years. INTERVENTIONS:
      Two consecutive ventilation periods (pressure support and neurally adjusted
      ventilatory assist) were applied in random order. During pressure support (PS),
      three levels of expiratory trigger (ETS) setting were compared: initial ETS
      (PSinit), and ETS value decreased and increased by 15%. Of the three sessions,
      the period allowing for the lowest number of asynchrony events was defined as
      PSbest. Neurally adjusted ventilator assist level was adjusted to match the
      maximum airway pressure during PSinit. Positive end-expiratory pressure was the
      same during pressure support and neurally adjusted ventilator assist. Asynchrony
      events, trigger delay, and cycling-off delay were quantified for each period.
      RESULTS: Six infants and children were studied. Trigger delay was lower with
      neurally adjusted ventilator assist versus PSinit and PSbest (61 ms [56-79] vs
      149 ms [134-180] and 146 ms [101-162]; p = 0.001 and 0.02, respectively).
      Inspiratory time in excess showed a trend to be shorter during pressure support
      versus neurally adjusted ventilator assist. Main asynchrony events during PSinit
      were autotriggering (4.8/min [1.7-12]), ineffective efforts (9.9/min [1.7-18]),
      and premature cycling (6.3/min [3.2-18.7]). Premature cycling (3.4/min [1.1-7.7])
      was less frequent during PSbest versus PSinit (p = 0.059). The asynchrony index
      was significantly lower during PSbest versus PSinit (40% [28-65] vs 65.5% [42
      76], p < 0.001). With neurally adjusted ventilator assist, all types of
      asynchronies except double triggering were reduced. The asynchrony index was
      lower with neurally adjusted ventilator assist (2.3% [0.7-5] vs PSinit and
      PSbest, p < 0.05 for both comparisons). CONCLUSION: Asynchrony events are
      frequent during noninvasive ventilation with pressure support in infants and in
      children despite adjusting the cycling-off criterion. Compared with pressure
      support, neurally adjusted ventilator assist allows improving patient-ventilator
      synchrony by reducing trigger delay and the number of asynchrony events. Further
      studies should determine the clinical impact of these findings.

PMID- 23863817
TI  - A comparison of quality improvement practices at adult and pediatric trauma
      centers*.
AB  - OBJECTIVES: Quality assurance practices are structured performance improvement
      and patient safety processes designed to continuously monitor, evaluate, and
      improve the performance of a trauma program. These practices are integral in the
      provision of quality injury care, and yet no comprehensive description of
      existing quality improvement practices used by pediatric trauma centers is
      available. Therefore, we compared the quality improvement programs used in adult
      and pediatric trauma centers by performing a reanalysis of our recent survey of
      trauma quality improvement practices in Canada, United States, Australia, and New
      Zealand. DESIGN: Prospective observational study. SETTING: Pediatric and adult
      trauma centers in United States, Canada, and Australasia. PATIENTS: None.
      INTERVENTIONS: None. MEASUREMENTS: We surveyed 184 trauma centers verified by
      professional trauma organizations in the United States, Canada, and Australasia
      regarding their quality improvement programs. Centers were classified according
      to population served (adult, adult and pediatric, or pediatric patients), and
      quality improvement programs were compared using descriptive statistics. RESULTS:
      Most of the trauma centers reported engagement in quality improvement activities.
      Adult centers devoted a larger percentage of their quality indicators to the
      measurement of safety (adult 50% vs adult and pediatric 53% vs pediatric 38%, p <
      0.001), whereas pediatric centers placed a greater emphasis on the timeliness of
      care (20% vs 24% vs 30%, p < 0.001). Few centers used quality indicators to
      measure the patient-centered nature of care, long-term outcomes, or secondary
      injury prevention. CONCLUSIONS: Opportunities for the improvement of pediatric
      quality improvement programs exist including a need to determine the optimal
      structure for trauma quality improvement, develop patient-centered quality
      indicators of injury care, measure long-term outcomes, and create measures of
      secondary injury prevention.

PMID- 23863818
TI  - Increasing use of hypertonic saline over mannitol in the treatment of symptomatic
      cerebral edema in pediatric diabetic ketoacidosis: an 11-year retrospective
      analysis of mortality*.
AB  - OBJECTIVES: Cerebral edema in diabetic ketoacidosis is a devastating complication
      with significant morbidity and mortality. This entity has traditionally been
      treated with mannitol, but use of 3% hypertonic saline has become an accepted
      alternative. We sought to assess if changes in the use of hyperosmolar therapies
      for treatment of cerebral edema in diabetic ketoacidosis may have influenced
      mortality over the last decade. DESIGN: Retrospective cohort study. SETTING:
      Patients discharged between 1999 and 2009 from 41 children's hospitals that
      provided data to the Pediatric Health Information System database. PATIENTS: A
      total of 43,107 children (age < 19) with diagnosis codes related to diabetic
      ketoacidosis were identified and further classified as having cerebral edema if
      treated with mannitol and/or 3% hypertonic saline. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Billing for 3% hypertonic saline and mannitol was
      quantified, and mortality associated with both diabetic ketoacidosis and cerebral
      edema in diabetic ketoacidosis was examined. Overall mortality in diabetic
      ketoacidosis was 0.25% and significantly decreased (p < 0.001) over the study
      period, whereas the frequency of treatment with hyperosmolar agents (3.8%) was
      unchanged. Use of mannitol as a sole agent decreased from 98% to 49%, 3%
      hypertonic saline as a sole agent increased from 2% to 39%, and combined therapy
      increased from 0% to 10%. Use of 3% hypertonic saline alone was associated with a
      higher mortality than mannitol alone (adjusted odds ratio, 2.71 [95% CI, 1.01
      7.26]) in patients treated for cerebral edema. Similar results were obtained
      after adjustment for the propensity to receive hypertonic saline (adjusted odds
      ratio, 2.33 [95% CI, 1.07-5.07]) and in the subset of subjects receiving
      mechanical ventilation (adjusted odds ratio, 3.27 [95% CI, 1.12-9.60]).
      CONCLUSION: Hypertonic saline has replaced mannitol as the most commonly used
      agent at many institutions for treatment of cerebral edema in diabetic
      ketoacidosis. In our analysis, however, use of hypertonic saline as a sole agent
      was associated with an increased risk of mortality. Recognizing the limitations
      of administrative data, we conclude that equipoise regarding choice of therapy
      for treatment of cerebral edema in diabetic ketoacidosis should be maintained
      until a more definitive study is performed to guide therapy of this potentially
      lethal complication.

PMID- 23863820
TI  - Hypoglycemia adverse events in PICUs and cardiac ICUs: differentiating
      preventable and nonpreventable events*.
AB  - OBJECTIVES: To describe the use of an adverse event detection system to identify,
      characterize, and categorize preventable versus nonpreventable hypoglycemia AEs
      in PICUs and cardiac ICUs. DESIGN: Retrospective observational study. SETTING:
      PICU and cardiac ICU of a tertiary pediatric hospital. SUBJECTS: All hypoglycemia
      triggers generated over a 3-year period. INTERVENTIONS: All hypoglycemia triggers
      generated via an electronic health record-driven surveillance system were
      investigated to determine if they represented a true adverse event and if that
      event was preventable or nonpreventable. Clinical and demographic variables were
      analyzed to identify characteristics of patients who developed a preventable or
      nonpreventable hypoglycemia adverse event. MEASUREMENTS AND MAIN RESULTS: There
      were 197 hypoglycemia adverse events in 90 patients. Thirty percent of the
      adverse events in the PICU and 36% of the adverse events in the cardiac ICU were
      characterized as preventable. Of the adverse events, 118 (59.9%) necessitated an
      intravenous dextrose bolus. No adverse events were associated with reporting of
      symptoms of hypoglycemia including apnea, altered mental status, or seizures.
      Events were more likely to be preventable (p < 0.001) if the patient was
      receiving only parenteral sources of nutrition (intravenous fluids or total
      parenteral nutrition). Controlling for weekends and holidays, adverse events
      associated with sole parenteral nutrition source had an increased odds ratio of
      9.5 (95% confidence interval: 2.8-31.9) of being preventable. Stratifying by ICU,
      cardiac ICU events occurring on a weekend or holiday were more likely to be
      preventable (p = 0.001). Stratifying by unit and controlling for parenteral
      nutrition source, adverse events in the cardiac ICU occurring on weekends or
      holidays had an increased odds ratio of 11.6 (95% confidence interval: 2.7-50.2)
      of being preventable. CONCLUSIONS: Preventable hypoglycemia adverse events are
      associated with patients receiving sole parenteral sources of nutrition in both
      the PICU and cardiac ICU. In the cardiac ICU, there is an association between
      weekend and holiday time periods and the development of preventable hypoglycemia
      adverse events.

PMID- 23863819
TI  - Differences in medical therapy goals for children with severe traumatic brain
      injury-an international study.
AB  - OBJECTIVES: To describe the differences in goals for their usual practice for
      various medical therapies from a number of international centers for children
      with severe traumatic brain injury. DESIGN: A survey of the goals from
      representatives of the international centers. SETTING: Thirty-two pediatric
      traumatic brain injury centers in the United States, United Kingdom, France, and
      Spain. PATIENTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A
      survey instrument was developed that required free-form responses from the
      centers regarding their usual practice goals for topics of intracranial
      hypertension therapies, hypoxia/ischemia prevention and detection, and metabolic
      support. Cerebrospinal fluid diversion strategies varied both across centers and
      within centers, with roughly equal proportion of centers adopting a strategy of
      continuous cerebrospinal fluid diversion and a strategy of no cerebrospinal fluid
      diversion. Use of mannitol and hypertonic saline for hyperosmolar therapies was
      widespread among centers (90.1% and 96.9%, respectively). Of centers using
      hypertonic saline, 3% saline preparations were the most common but many other
      concentrations were in common use. Routine hyperventilation was not reported as a
      standard goal and 31.3% of centers currently use PbO(2) monitoring for cerebral
      hypoxia. The time to start nutritional support and glucose administration varied
      widely, with nutritional support beginning before 96 hours and glucose
      administration being started earlier in most centers. CONCLUSIONS: There were
      marked differences in medical goals for children with severe traumatic brain
      injury across our international consortium, and these differences seemed to be
      greatest in areas with the weakest evidence in the literature. Future studies
      that determine the superiority of the various medical therapies outlined within
      our survey would be a significant advance for the pediatric neurotrauma field and
      may lead to new standards of care and improved study designs for clinical trials.

PMID- 23863821
TI  - Paediatric index of mortality 3: an updated model for predicting mortality in
      pediatric intensive care*.
AB  - OBJECTIVES: To provide an updated version of the Paediatric Index of Mortality 2
      for assessing the risk of mortality among children admitted to an ICU. DESIGN:
      International, multicenter, prospective cohort study. SETTING: Sixty ICUs that
      accept pediatric admissions in Australia, New Zealand, Ireland, and the United
      Kingdom. PATIENTS: All children admitted in 2010 and 2011 younger than 18 years
      old at the time of admission and either died in ICU or were discharged. Patients
      who were transferred to another ICU were not included. Fifty-three thousand one
      hundred twelve patient admissions were included in the analysis. INTERVENTIONS:
      None. MEASUREMENT AND MAIN RESULTS: A revised prediction model was built using
      logistic regression. Variable selection was based on significance at the 95%
      level and overall improvement of the model's discriminatory performance and
      goodness of fit. The final model discriminated well (area under the curve, 0.88,
      0.88-0.89); however, the model performed better in Australia and New Zealand than
      in the United Kingdom and Ireland (area under the curve was 0.91, 0.90-0.93 and
      0.85, 0.84-0.86, respectively). CONCLUSIONS: Paediatric Index of Mortality 3
      provides an international standard based on a large contemporary dataset for the
      comparison of risk-adjusted mortality among children admitted to intensive care.

PMID- 23863822
TI  - Survival of newborn infants with severe respiratory failure before and after
      establishing an extracorporeal membrane oxygenation program.
AB  - BACKGROUND: Severe hypoxic respiratory failure is a leading cause of neonatal
      mortality in Chile. Extracorporeal membrane oxygenation improves survival in
      neonates with hypoxic respiratory failure. OBJECTIVE: To determine the impact of
      the establishment of a Neonatal Extracorporeal Membrane Oxygenation Program on
      the outcome of newborns with severe hypoxic respiratory failure in a developing
      country. DESIGN/PATIENTS: Data of newborns (birthweight > 2,000 g and gestational
      age >= 35 wk) with hypoxic respiratory failure and oxygenation index greater than
      25 were compared before and after extracorporeal membrane oxygenation was
      available. Extracorporeal membrane oxygenation was initiated in infants with
      refractory hypoxic respiratory failure who failed to respond to inhaled nitric
      oxide/high-frequency oscillatory ventilation. MAIN RESULTS: Data from 259 infants
      were analyzed; 100 born in the pre-extracorporeal membrane oxygenation period and
      159 born after the extracorporeal membrane oxygenation program was established.
      Patients were similar in terms of risk factors for death for both periods except
      for a higher oxygenation index and a greater proportion of outborn infants during
      the extracorporeal membrane oxygenation period. Survival significantly increased
      from 72% before extracorporeal membrane oxygenation to 89% during the
      extracorporeal membrane oxygenation period (p < 0.01). During the extracorporeal
      membrane oxygenation period, 98 of 159 patients (62%) with hypoxic respiratory
      failure were rescued using inhaled nitric oxide/high-frequency oscillatory
      ventilation, whereas 61 (38%) did not improve; 52 of these 61 neonates were
      placed on extracorporeal membrane oxygenation. Extracorporeal membrane
      oxygenation survival rate to discharge was 85%. After adjusting for potential
      confounders, the severity of the pretreatment oxygenation index, a late arrival
      to the referral center, the presence of a pneumothorax, and the diagnosis of a
      diaphragmatic hernia were significantly associated with the need for
      extracorporeal membrane oxygenation or death. CONCLUSIONS: The establishment of
      an extracorporeal membrane oxygenation program was associated with a significant
      increase in the survival of newborns more than or equal to 35 weeks old with
      severe hypoxic respiratory failure.

PMID- 23863823
TI  - Improving delivery of continuous renal replacement therapy: impact of a
      simulation-based educational intervention.
AB  - PURPOSE: To describe our experience with transitions in both nursing model and
      educational training program for delivery of continuous renal replacement
      therapy. There have been very few comparisons between different care and
      educational models, and the optimal approach remains uncertain. In particular, we
      evaluated our experience with introducing a simulation-based educational model.
      DESIGN: Prospective quality control observational study. SETTING: The ICU of a
      tertiary care pediatric referral center. PATIENTS: All patients undergoing CRRT
      between July 2007 through July 2010 were included. MEASUREMENTS AND MAIN RESULTS:
      We monitored CRRT filter life during a transition from a collaborative to
      critical care nursing model, and subsequently during a transition from a didactic
      education program to simulation-based training. During the study period, 80
      patients underwent continuous renal replacement therapy with use of 343 filters.
      Process control charts demonstrated a significant increase in filter life and a
      decrease in unplanned filter changes. Both of these signals emerged at the same
      time and corresponded with the introduction of the simulation-based education
      program. Further statistical analysis showed that filter life improved from 42.5
      hours (18.2-66.4 hr) during the didactic education program to 59.4 hours (22.2
      76.4 hr) during the simulation-based education program (p = 0.008). This
      relationship persisted when excluding nonpreventable premature filter
      discontinuations and in a multivariate model that accounted for other potential
      influences on filter life. CONCLUSIONS: We report on the impact of transitioning
      between different educational programs for continuous renal replacement therapy,
      specifically with the introduction of a simulation-based approach. We observed a
      significant and sustained improvement in the delivery of continuous renal
      replacement therapy as demonstrated by a marked increase in filter lifespan.

PMID- 23863824
TI  - Use of disulfiram and risk of cancer: a population-based case-control study.
AB  - Experimental studies have indicated that disulfiram (Antabuse) has antineoplastic
      effects against melanoma, breast, and prostate cancer. To explore this
      hypothesis, we examined the association between disulfiram use and these cancers
      in a nationwide register-based case-control study nested within ever-users (>=one
      prescription) of disulfiram. Cases were all Danish individuals with a
      histologically verified first-time diagnosis of malignant melanoma, breast, or
      prostate cancer during 2000-2009. For each case, we selected four cancer-free
      controls matched for age, sex, and year of first disulfiram prescription using
      risk set sampling. Similarly, for secondary analyses, we selected case-control
      populations for selected tobacco-related and alcohol-related cancer types, that
      is, cancers of the buccal cavity, liver, lung, and colorectal cancer. Disulfiram
      use 1 year before cancer diagnosis and the corresponding date for controls were
      disregarded. We estimated crude and adjusted odds ratios and 95% confidence
      intervals (CI) for cancer associated with long-term (>=500 daily defined doses)
      versus one-time (one prescription) use of disulfiram. Among 53 856 disulfiram
      users, we identified 166, 644, and 464 cases, respectively, of melanoma, breast,
      or prostate cancer. Adjusted odds ratios for melanoma, breast, or prostate cancer
      associated with long-term disulfiram use were 1.04 (95% CI: 0.60-1.78), 0.92 (95%
      CI: 0.70-1.22), and 0.77 (95% CI: 0.56-1.06), respectively. For prostate cancer,
      dose-response analyses showed a further risk reduction with the highest
      cumulative dose level of disulfiram; however, the test for trend did not reach
      statistical significance. Our study provides some epidemiological support for a
      protective effect of disulfiram against prostate and breast cancer. 

PMID- 23863825
TI  - Dairy products, dietary calcium and bone health: possibility of prevention of
      osteoporosis in women: the Polish experience.
AB  - The objective of the study was to analyze the consumption of dairy products and
      dietary calcium by women in the context of bone mineral density and to assess
      opportunities to prevent osteoporosis in a dietary manner. The study was carried
      out with 712 Polish women. In 170 women aged 32 to 59 bone mineral density (BMD)
      was measured. The data on the consumption of dairy products and dietary calcium
      and some other osteoporosis risk factors was collected from 712 women. The
      average calcium intake from a diet was 507 mg/day. Only 2% of the women met
      Polish calcium intake recommendations. During adulthood, dairy product
      consumption or dietary calcium intake did not differ significantly between women
      with low BMD (below -1 SD) and women with regular BMD (>=-1 SD) (47.4 vs. 44.3
      servings/week and 459 vs. 510 mg/day, respectively, p > 0.05). The odds ratios
      adjusted for age, menstruation and BMI in women with upper BMD tercile in
      comparison to the reference group (bottom tercile) was 2.73 (95% CI: 1.14, 6.55;
      p < 0.05) for the daily consumption of dairy products during the pre-school
      period and 2.40 (95% CI: 1.01, 5.70; p < 0.05) for the daily consumption of dairy
      products during the school period. Two clusters of women were established. In the
      S1 cluster, low BMD (below -1 SD) was associated with older age (>= 50 years),
      lack of menstrual cycle. In the S2 cluster, regular BMD (>=-1 SD) was related to
      younger aged women (<50 years), presence of menstrual cycle, consumption of
      higher level of dairy products (>=28 servings/week) during adulthood and daily
      intake of dairy products during childhood and adolescence. The results indicate
      that good bone health to the larg e extent depended upon the combined impact of
      dietary factors and some non-modifiable risk factors of osteoporosis such as age
      and the presence of menstruation. Consumption of dairy products in childhood and
      adolescence may improve bone mineral density and reduce the risk of osteoporosis
      in adult women.

PMID- 23863828
TI  - Feasibility of virtual reality augmented cycling for health promotion of people
      poststroke.
AB  - BACKGROUND AND PURPOSE: A virtual reality (VR) augmented cycling kit (VRACK) was
      developed to address motor control and fitness deficits of individuals with
      chronic stroke. In this article, we report on the safety, feasibility, and
      efficacy of using the VR augmented cycling kit to improve cardiorespiratory (CR)
      fitness of individuals in the chronic phase poststroke. METHODS: Four individuals
      with chronic stroke (47-65 years old and >=3 years poststroke), with residual
      lower extremity impairments (Fugl-Meyer 24-26/34), who were limited community
      ambulators (gait speed range 0.56-1.1 m/s) participated in this study. Safety was
      defined as the absence of adverse events. Feasibility was measured using
      attendance, total exercise time, and "involvement" measured with the presence
      questionnaire (PQ). Efficacy of CR fitness was evaluated using a submaximal
      bicycle ergometer test before and after an 8-week training program. RESULTS: The
      intervention was safe and feasible with participants having 1 adverse event, 100%
      adherence, achieving between 90 and 125 minutes of cycling each week, and a mean
      PQ score of 39 (SD 3.3). There was a statistically significant (13%; P = 0.035)
      improvement in peak VO(2), with a range of 6% to 24.5%. DISCUSSION AND
      CONCLUSION: For these individuals, poststroke, VR augmented cycling, using their
      heart rate to set their avatar's speed, fostered training of sufficient duration
      and intensity to promote CR fitness. In addition, there was a transfer of
      training from the bicycle to walking endurance. VR augmented cycling may be an
      addition to the therapist's tools for concurrent training of mobility and health
      promotion of individuals poststroke.

PMID- 23863826
TI  - Obesity and dyslipidemia in South Asians.
AB  - Obesity and dyslipidemia are emerging as major public health challenges in South
      Asian countries. The prevalence of obesity is more in urban areas than rural, and
      women are more affected than men. Further, obesity in childhood and adolescents
      is rising rapidly. Obesity in South Asians has characteristic features: high
      prevalence of abdominal obesity, with more intra-abdominal and truncal
      subcutaneous adiposity than white Caucasians. In addition, there is greater
      accumulation of fat at "ectopic" sites, namely the liver and skeletal muscles.
      All these features lead to higher magnitude of insulin resistance, and its
      concomitant metabolic disorders (the metabolic syndrome) including atherogenic
      dyslipidemia. Because of the occurrence of type 2 diabetes, dyslipidemia and
      other cardiovascular morbidities at a lower range of body mass index (BMI) and
      waist circumference (WC), it is proposed that cut-offs for both measures of
      obesity should be lower (BMI 23-24.9 kg/m(2) for overweight and >= 25 kg/m(2) for
      obesity, WC >= 80 cm for women and >= 90 cm for men for abdominal obesity) for
      South Asians, and a consensus guideline for these revised measures has been
      developed for Asian Indians. Increasing obesity and dyslipidemia in South Asians
      is primarily driven by nutrition, lifestyle and demographic transitions,
      increasingly faulty diets and physical inactivity, in the background of genetic
      predisposition. Dietary guidelines for prevention of obesity and diabetes, and
      physical activity guidelines for Asian Indians are now available. Intervention
      programs with emphasis on improving knowledge, attitude and practices regarding
      healthy nutrition, physical activity and stress management need to be
      implemented. Evidence for successful intervention program for prevention of
      childhood obesity and for prevention of diabetes is available for Asian Indians,
      and could be applied to all South Asian countries with similar cultural and
      lifestyle profiles. Finally, more research on pathophysiology, guidelines for cut
      offs, and culturally-specific lifestyle management of obesity, dyslipidemia and
      the metabolic syndrome are needed for South Asians.

PMID- 23863829
TI  - Genomics in clinical practice: lessons from the front lines.
AB  - The price of whole-genome and -exome sequencing has fallen to the point where
      these methods can be applied to clinical medicine. Here, we outline the lessons
      we have learned in converting a sequencing laboratory designed for research into
      a fully functional clinical program. 

PMID- 23863830
TI  - Incidental swimming with millstones.

PMID- 23863831
TI  - Vector decoys trick the immune response.
AB  - Humoral immunity to adeno-associated viral vectors can be overcome by using empty
      capsid mutant "decoys" for preexisting antibodies (Mingozzi et al., this issue). 

PMID- 23863833
TI  - Intraoperative tissue identification using rapid evaporative ionization mass
      spectrometry.
AB  - Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique
      that allows near-real-time characterization of human tissue in vivo by analysis
      of the aerosol ("smoke") released during electrosurgical dissection. The coupling
      of REIMS technology with electrosurgery for tissue diagnostics is known as the
      intelligent knife (iKnife). This study aimed to validate the technique by
      applying it to the analysis of fresh human tissue samples ex vivo and to
      demonstrate the translation to real-time use in vivo in a surgical environment. A
      variety of tissue samples from 302 patients were analyzed in the laboratory,
      resulting in 1624 cancerous and 1309 noncancerous database entries. The
      technology was then transferred to the operating theater, where the device was
      coupled to existing electrosurgical equipment to collect data during a total of
      81 resections. Mass spectrometric data were analyzed using multivariate
      statistical methods, including principal components analysis (PCA) and linear
      discriminant analysis (LDA), and a spectral identification algorithm using a
      similar approach was implemented. The REIMS approach differentiated accurately
      between distinct histological and histopathological tissue types, with malignant
      tissues yielding chemical characteristics specific to their histopathological
      subtypes. Tissue identification via intraoperative REIMS matched the
      postoperative histological diagnosis in 100% (all 81) of the cases studied. The
      mass spectra reflected lipidomic profiles that varied between distinct
      histological tumor types and also between primary and metastatic tumors. Thus, in
      addition to real-time diagnostic information, the spectra provided additional
      information on divergent tumor biochemistry that may have mechanistic importance
      in cancer. 

PMID- 23863834
TI  - Changes in amyloid-beta and Tau in the cerebrospinal fluid of transgenic mice
      overexpressing amyloid precursor protein.
AB  - Altered concentrations of amyloid-beta (Abeta) peptide and Tau protein in the
      cerebrospinal fluid (CSF) are thought to be predictive markers for Alzheimer's
      disease (AD). Transgenic mice overexpressing human amyloid precursor protein
      (APP) have been used to model Abeta pathology, but concomitant changes in Abeta
      and Tau in CSF have been less well studied. We measured Abeta and Tau in the
      brains and CSF of two well-characterized transgenic mouse models of AD: one
      expressing human APP carrying the Swedish mutation (APP23) and the other
      expressing mutant human APP and mutant human presenilin-1 (APPPS1). Both mouse
      models exhibit Abeta deposition in the brain, but with different onset and
      progression trajectories. We found an age-related 50 to 80% decrease in Abeta42
      peptide in mouse CSF and a smaller decrease in Abeta40, both inversely correlated
      with the brain Abeta load. Surprisingly, the same mice showed a threefold
      increase in total endogenous murine Tau in CSF at the stages when Abeta pathology
      became prominent. The results mirror the temporal sequence and magnitude of Abeta
      and Tau changes in the CSF of patients with sporadic and dominantly inherited AD.
      This observation indicates that APP transgenic mice may be useful as a
      translational tool for predicting changes in Abeta and Tau markers in the CSF of
      AD patients. These findings also suggest that APP transgenic mouse models may be
      useful in the search for new disease markers for AD. 

PMID- 23863832
TI  - Overcoming preexisting humoral immunity to AAV using capsid decoys.
AB  - Adeno-associated virus (AAV) vectors delivered through the systemic circulation
      successfully transduce various target tissues in animal models. However, similar
      attempts in humans have been hampered by the high prevalence of neutralizing
      antibodies to AAV, which completely block vector transduction. We show in both
      mouse and nonhuman primate models that addition of empty capsid to the final
      vector formulation can, in a dose-dependent manner, adsorb these antibodies, even
      at high titers, thus overcoming their inhibitory effect. To further enhance the
      safety of the approach, we mutated the receptor binding site of AAV2 to generate
      an empty capsid mutant that can adsorb antibodies but cannot enter a target cell.
      Our work suggests that optimizing the ratio of full/empty capsids in the final
      formulation of vector, based on a patient's anti-AAV titers, will maximize the
      efficacy of gene transfer after systemic vector delivery. 

PMID- 23863835
TI  - Differences in viral load testing methodology may play an important role in
      optimizing the initial management of HIV-infected pregnant women.

PMID- 23863836
TI  - HnRNP A1 controls a splicing regulatory circuit promoting mesenchymal-to
      epithelial transition.
AB  - Epithelial-to-mesenchymal transition (EMT) is an embryonic program used by cancer
      cells to acquire invasive capabilities becoming metastatic. DeltaRon, a
      constitutively active isoform of the Ron tyrosine kinase receptor, arises from
      skipping of Ron exon 11 and provided the first example of an alternative splicing
      variant causatively linked to the activation of tumor EMT. Splicing of exon 11 is
      controlled by two adjacent regulatory elements, a silencer and an enhancer of
      splicing located in exon 12. The alternative splicing factor and oncoprotein
      SRSF1 directly binds to the enhancer, induces the production of DeltaRon and
      activates EMT leading to cell locomotion. Interestingly, we now find an important
      role for hnRNP A1 in controlling the activity of the Ron silencer. HnRNP A1 is
      able to antagonize the binding of SRSF1 and prevent exon skipping. Notably, hnRNP
      A1, by inhibiting the production of DeltaRon, activates the reversal program,
      namely the mesenchymal-to-epithelial transition, which instead occurs at the
      final metastasis sites. Also, hnRNP A1 affects Ron splicing by regulating the
      expression level of hnRNP A2/B1, which similarly to SRSF1 can promote DeltaRon
      production. These results shed light on how splicing regulation contributes to
      the tumor progression and provide potential targets to develop anticancer
      therapies. 

PMID- 23863837
TI  - CRISPRmap: an automated classification of repeat conservation in prokaryotic
      adaptive immune systems.
AB  - Central to Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas
      systems are repeated RNA sequences that serve as Cas-protein-binding templates.
      Classification is based on the architectural composition of associated Cas
      proteins, considering repeat evolution is essential to complete the picture. We
      compiled the largest data set of CRISPRs to date, performed comprehensive,
      independent clustering analyses and identified a novel set of 40 conserved
      sequence families and 33 potential structure motifs for Cas-endoribonucleases
      with some distinct conservation patterns. Evolutionary relationships are
      presented as a hierarchical map of sequence and structure similarities for both a
      quick and detailed insight into the diversity of CRISPR-Cas systems. In a
      comparison with Cas-subtypes, I-C, I-E, I-F and type II were strongly coupled and
      the remaining type I and type III subtypes were loosely coupled to repeat and
      Cas1 evolution, respectively. Subtypes with a strong link to CRISPR evolution
      were almost exclusive to bacteria; nevertheless, we identified rare examples of
      potential horizontal transfer of I-C and I-E systems into archaeal organisms. Our
      easy-to-use web server provides an automated assignment of newly sequenced
      CRISPRs to our classification system and enables more informed choices on future
      hypotheses in CRISPR-Cas research: http://rna.informatik.uni
      freiburg.de/CRISPRmap. 

PMID- 23863838
TI  - miRISC recruits decapping factors to miRNA targets to enhance their degradation.
AB  - MicroRNA (miRNA)-induced silencing complexes (miRISCs) repress translation and
      promote degradation of miRNA targets. Target degradation occurs through the 5'-to
      3' messenger RNA (mRNA) decay pathway, wherein, after shortening of the mRNA
      poly(A) tail, the removal of the 5' cap structure by decapping triggers
      irreversible decay of the mRNA body. Here, we demonstrate that miRISC enhances
      the association of the decapping activators DCP1, Me31B and HPat with
      deadenylated miRNA targets that accumulate when decapping is blocked. DCP1 and
      Me31B recruitment by miRISC occurs before the completion of deadenylation.
      Remarkably, miRISC recruits DCP1, Me31B and HPat to engineered miRNA targets
      transcribed by RNA polymerase III, which lack a cap structure, a protein-coding
      region and a poly(A) tail. Furthermore, miRISC can trigger decapping and the
      subsequent degradation of mRNA targets independently of ongoing deadenylation.
      Thus, miRISC increases the local concentration of the decapping machinery on
      miRNA targets to facilitate decapping and irreversibly shut down their
      translation. 

PMID- 23863839
TI  - Analysis of epigenetic stability and conversions in Saccharomyces cerevisiae
      reveals a novel role of CAF-I in position-effect variegation.
AB  - Position-effect variegation (PEV) phenotypes are characterized by the robust
      multigenerational repression of a gene located at a certain locus (often called
      gene silencing) and occasional conversions to fully active state. Consequently,
      the active state then persists with occasional conversions to the repressed
      state. These effects are mediated by the establishment and maintenance of
      heterochromatin or euchromatin structures, respectively. In this study, we have
      addressed an important but often neglected aspect of PEV: the frequency of
      conversions at such loci. We have developed a model and have projected various
      PEV scenarios based on various rates of conversions. We have also enhanced two
      existing assays for gene silencing in Saccharomyces cerevisiae to measure the
      rate of switches from repressed to active state and vice versa. We tested the
      validity of our methodology in Deltasir1 cells and in several mutants with
      defects in gene silencing. The assays have revealed that the histone chaperone
      Chromatin Assembly Factor I is involved in the control of epigenetic conversions.
      Together, our model and assays provide a comprehensive methodology for further
      investigation of epigenetic stability and position effects. 

PMID- 23863840
TI  - A competitive regulatory mechanism discriminates between juxtaposed splice sites
      and pri-miRNA structures.
AB  - We have explored the functional relationships between spliceosome and
      Microprocessor complex activities in a novel class of microRNAs (miRNAs), named
      Splice site Overlapping (SO) miRNAs, whose pri-miRNA hairpins overlap splice
      sites. We focused on the evolutionarily conserved SO miR-34b, and we identified
      two indispensable elements for recognition of its 3' splice site: a branch point
      located in the hairpin and a downstream purine-rich exonic splicing enhancer. In
      minigene systems, splicing inhibition owing to exonic splicing enhancer deletion
      or AG 3'ss mutation increases miR-34b levels. Moreover, small interfering
      mediated silencing of Drosha and/or DGCR8 improves splicing efficiency and
      abolishes miR-34b production. Thus, the processing of this 3' SO miRNA is
      regulated in an antagonistic manner by the Microprocessor and the spliceosome
      owing to competition between these two machineries for the nascent transcript. We
      propose that this novel mechanism is commonly used to regulate the relative
      amount of SO miRNA and messenger RNA produced from primary transcripts. 

PMID- 23863841
TI  - Type III restriction-modification enzymes: a historical perspective.
AB  - Restriction endonucleases interact with DNA at specific sites leading to cleavage
      of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by
      modifying the DNA using a DNA methyltransferase. Based on their molecular
      structure, sequence recognition, cleavage position and cofactor requirements,
      restriction-modification (R-M) systems are classified into four groups. Type III
      R-M enzymes need to interact with two separate unmethylated DNA sequences in
      inversely repeated head-to-head orientations for efficient cleavage to occur at a
      defined location (25-27 bp downstream of one of the recognition sites). Like the
      Type I R-M enzymes, Type III R-M enzymes possess a sequence-specific ATPase
      activity for DNA cleavage. ATP hydrolysis is required for the long-distance
      communication between the sites before cleavage. Different models, based on 1D
      diffusion and/or 3D-DNA looping, exist to explain how the long-distance
      interaction between the two recognition sites takes place. Type III R-M systems
      are found in most sequenced bacteria. Genome sequencing of many pathogenic
      bacteria also shows the presence of a number of phase-variable Type III R-M
      systems, which play a role in virulence. A growing number of these enzymes are
      being subjected to biochemical and genetic studies, which, when combined with
      ongoing structural analyses, promise to provide details for mechanisms of DNA
      recognition and catalysis. 

PMID- 23863842
TI  - BRCA1 is a key regulator of breast differentiation through activation of Notch
      signalling with implications for anti-endocrine treatment of breast cancers.
AB  - Here, we show for the first time, that the familial breast/ovarian cancer
      susceptibility gene BRCA1 activates the Notch pathway in breast cells by
      transcriptional upregulation of Notch ligands and receptors in both normal and
      cancer cells. We demonstrate through chromatin immunoprecipitation assays that
      BRCA1 is localized to a conserved intronic enhancer region within the Notch
      ligand Jagged-1 (JAG1) gene, an event requiring DeltaNp63. We propose that this
      BRCA1/DeltaNp63-mediated induction of JAG1 may be important the regulation of
      breast stem/precursor cells, as knockdown of all three proteins resulted in
      increased tumoursphere growth and increased activity of stem cell markers such as
      Aldehyde Dehydrogenase 1 (ALDH1). Knockdown of Notch1 and JAG1 phenocopied BRCA1
      knockdown resulting in the loss of Estrogen Receptor-alpha (ER-alpha) expression
      and other luminal markers. A Notch mimetic peptide could activate an ER-alpha
      promoter reporter in a BRCA1-dependent manner, whereas Notch inhibition using a
      gamma-secretase inhibitor reversed this process. We demonstrate that inhibition
      of Notch signalling resulted in decreased sensitivity to the anti-estrogen drug
      Tamoxifen but increased expression of markers associated with basal-like breast
      cancer. Together, these findings suggest that BRCA1 transcriptional upregulation
      of Notch signalling is a key event in the normal differentiation process in
      breast tissue. 

PMID- 23863814
TI  - Acceleration of the loss of the first-phase insulin response during the
      progression to type 1 diabetes in diabetes prevention trial-type 1 participants.
AB  - We studied the change in the first-phase insulin response (FPIR) during the
      progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors
      to T1D from the Diabetes Prevention Trial-Type 1 with at least one FPIR
      measurement after baseline and before diagnosis were studied. The FPIR was
      examined longitudinally in 26 progressors who had FPIR measurements during each
      of the 3 years before diagnosis. The association between the change from the
      baseline FPIR to the last FPIR and time to diagnosis was studied in the remainder
      (n = 48). The 74 progressors had lower baseline FPIR values than nonprogressors
      (n = 270), with adjustments made for age and BMI. In the longitudinal analysis of
      the 26 progressors, there was a greater decline in the FPIR from 1.5 to 0.5 years
      before diagnosis than from 2.5 to 1.5 years before diagnosis. This accelerated
      decline was also evident in a regression analysis of the 48 remaining progressors
      in whom the rate of decline became more marked with the approaching diagnosis.
      The patterns of decline were similar between the longitudinal and regression
      analyses. There is an acceleration of decline in the FPIR during the progression
      to T1D, which becomes especially marked between 1.5 and 0.5 years before
      diagnosis. 

PMID- 23863843
TI  - Modulation of base excision repair of 8-oxoguanine by the nucleotide sequence.
AB  - 8-Oxoguanine (8-oxoG) is a major product of oxidative DNA damage, which induces
      replication errors and interferes with transcription. By varying the position of
      single 8-oxoG in a functional gene and manipulating the nucleotide sequence
      surrounding the lesion, we found that the degree of transcriptional inhibition is
      independent of the distance from the transcription start or the localization
      within the transcribed or the non-transcribed DNA strand. However, it is strongly
      dependent on the sequence context and also proportional to cellular expression of
      8-oxoguanine DNA glycosylase (OGG1)-demonstrating that transcriptional arrest
      does not take place at unrepaired 8-oxoG and proving a causal connection between
      8-oxoG excision and the inhibition of transcription. We identified the 5'
      CAGGGC[8-oxoG]GACTG-3' motif as having only minimal transcription-inhibitory
      potential in cells, based on which we predicted that 8-oxoG excision is
      particularly inefficient in this sequence context. This anticipation was fully
      confirmed by direct biochemical assays. Furthermore, in DNA containing a
      bistranded Cp[8-oxoG]/Cp[8-oxoG] clustered lesion, the excision rates differed
      between the two strands at least by a factor of 9, clearly demonstrating that the
      excision preference is defined by the DNA strand asymmetry rather than the
      overall geometry of the double helix or local duplex stability. 

PMID- 23863844
TI  - MREdictor: a two-step dynamic interaction model that accounts for mRNA
      accessibility and Pumilio binding accurately predicts microRNA targets.
AB  - The prediction of pairing between microRNAs (miRNAs) and the miRNA recognition
      elements (MREs) on mRNAs is expected to be an important tool for understanding
      gene regulation. Here, we show that mRNAs that contain Pumilio recognition
      elements (PRE) in the proximity of predicted miRNA-binding sites are more likely
      to form stable secondary structures within their 3'-UTR, and we demonstrated
      using a PUM1 and PUM2 double knockdown that Pumilio proteins are general
      regulators of miRNA accessibility. On the basis of these findings, we developed a
      computational method for predicting miRNA targets that accounts for the presence
      of PRE in the proximity of seed-match sequences within poorly accessible
      structures. Moreover, we implement the miRNA-MRE duplex pairing as a two-step
      model, which better fits the available structural data. This algorithm, called
      MREdictor, allows for the identification of miRNA targets in poorly accessible
      regions and is not restricted to a perfect seed-match; these features are not
      present in other computational prediction methods. 

PMID- 23863845
TI  - Structural studies of p53 inactivation by DNA-contact mutations and its rescue by
      suppressor mutations via alternative protein-DNA interactions.
AB  - A p53 hot-spot mutation found frequently in human cancer is the replacement of
      R273 by histidine or cysteine residues resulting in p53 loss of function as a
      tumor suppressor. These mutants can be reactivated by the incorporation of second
      site suppressor mutations. Here, we present high-resolution crystal structures of
      the p53 core domains of the cancer-related proteins, the rescued proteins and
      their complexes with DNA. The structures show that inactivation of p53 results
      from the incapacity of the mutated residues to form stabilizing interactions with
      the DNA backbone, and that reactivation is achieved through alternative
      interactions formed by the suppressor mutations. Detailed structural and
      computational analysis demonstrates that the rescued p53 complexes are not fully
      restored in terms of DNA structure and its interface with p53. Contrary to our
      previously studied wild-type (wt) p53-DNA complexes showing non-canonical
      Hoogsteen A/T base pairs of the DNA helix that lead to local minor-groove
      narrowing and enhanced electrostatic interactions with p53, the current
      structures display Watson-Crick base pairs associated with direct or water
      mediated hydrogen bonds with p53 at the minor groove. These findings highlight
      the pivotal role played by R273 residues in supporting the unique geometry of the
      DNA target and its sequence-specific complex with p53. 

PMID- 23863846
TI  - Controlling the stoichiometry and strand polarity of a tetramolecular G
      quadruplex structure by using a DNA origami frame.
AB  - Guanine-rich oligonucleotides often show a strong tendency to form supramolecular
      architecture, the so-called G-quadruplex structure. Because of the biological
      significance, it is now considered to be one of the most important conformations
      of DNA. Here, we describe the direct visualization and single-molecule analysis
      of the formation of a tetramolecular G-quadruplex in KCl solution. The
      conformational changes were carried out by incorporating two duplex DNAs, with G
      G mismatch repeats in the middle, inside a DNA origami frame and monitoring the
      topology change of the strands. In the absence of KCl, incorporated duplexes had
      no interaction and laid parallel to each other. Addition of KCl induced the
      formation of a G-quadruplex structure by stably binding the duplexes to each
      other in the middle. Such a quadruplex formation allowed the DNA synapsis without
      disturbing the duplex regions of the participating sequences, and resulted in an
      X-shaped structure that was monitored by atomic force microscopy. Further, the G
      quadruplex formation in KCl solution and its disruption in KCl-free buffer were
      analyzed in real-time. The orientation of the G-quadruplex is often difficult to
      control and investigate using traditional biochemical methods. However, our
      method using DNA origami could successfully control the strand orientations,
      topology and stoichiometry of the G-quadruplex. 

PMID- 23863847
TI  - The ubiquitin specific protease USP34 promotes ubiquitin signaling at DNA double
      strand breaks.
AB  - Ubiquitylation plays key roles in DNA damage signal transduction. The current
      model envisions that lysine63-linked ubiquitin chains, via the concerted action
      of E3 ubiquitin ligases RNF8-RNF168, are built at DNA double-strand breaks (DSBs)
      to effectively assemble DNA damage-repair factors for proper checkpoint control
      and DNA repair. We found that RNF168 is a short-lived protein that is stabilized
      by the deubiquitylating enzyme USP34 in response to DNA damage. In the absence of
      USP34, RNF168 is rapidly degraded, resulting in attenuated DSB-associated
      ubiquitylation, defective recruitment of BRCA1 and 53BP1 and compromised cell
      survival after ionizing radiation. We propose that USP34 promotes a feed-forward
      loop to enforce ubiquitin signaling at DSBs and highlight critical roles of
      ubiquitin dynamics in genome stability maintenance. 

PMID- 23863848
TI  - In situ fabrication of porous MoS2 thin-films as high-performance catalysts for
      electrochemical hydrogen evolution.
AB  - Amorphous MoS2 porous thin films (denoted as MoS2 PTFs) with high activity
      towards hydrogen evolution reaction (HER) were fabricated by in situ sulfuration
      of a Mo substrate. A small overpotential (~120 mV) and a low Tafel slope (~41 mV
      dec(-1)) can be observed and their excellent performance was ascribed to the
      combination of the amorphous feature, porous structure and optimized thickness.

PMID- 23863849
TI  - Trends in meniscus repair and meniscectomy in the United States, 2005-2011.
AB  - BACKGROUND: Meniscus deficiency may lead to degenerative arthritis in the knee.
      There is a significant emphasis on meniscus preservation, particularly in the
      young patient, to reduce the risk of arthritis. PURPOSE: To report on the
      incidence of meniscus repair and meniscectomy, with and without concomitant
      anterior cruciate ligament (ACL) reconstruction, in the United States (US) over
      the past 7 years. STUDY DESIGN: Descriptive epidemiology study. METHODS: Patients
      who underwent arthroscopic meniscectomy (Current Procedural Terminology [CPT]
      codes 29880 and 29881), meniscus repair (CPT codes 29882 and 29883), and ACL
      reconstruction (CPT code 29888) for the years 2005 through 2011 were identified
      using the PearlDiver Patient Record Database. Age group and sex were collected
      for each patient. Patient groups included meniscectomy alone, meniscus repair
      alone, meniscus repair followed by meniscectomy, ACL reconstruction with
      concomitant meniscus repair, and ACL reconstruction with concomitant meniscus
      repair followed by meniscectomy. Linear regression and Student t tests were
      utilized for comparisons, with an alpha value of .05 set as significant. RESULTS:
      The database represented approximately 9% of the US population under 65 years of
      age. There was no significant change in the number of patients in the covered
      population during the study time frame (P = .138). From 2005 to 2011, there were
      a total of 387,833 meniscectomies, 23,640 meniscus repairs, and 84,927 ACL
      reconstructions. There was a significant increase in the total number of isolated
      meniscus repairs performed (P = .001) and a doubling of the incidence of repairs
      from 2005 to 2011. There was no significant increase in the total number of
      meniscectomies performed (P = .712), while the incidence of meniscectomies
      increased only 14% from 2005 to 2011. There was no significant change in the
      number of meniscus repairs performed at the same time as ACL reconstruction
      during the study time frame. The total number and incidence of meniscectomies
      after repair with and without ACL reconstruction significantly decreased.
      CONCLUSION: There has been an increased number of isolated meniscus repairs being
      performed in the US over the past 7 years without a concomitant increase in
      meniscectomies over the same time frame. These data suggest that meniscus repairs
      are preferentially being performed over meniscectomies.

PMID- 23863851
TI  - Individualizing standardized tests: physiotherapists' and occupational
      therapists' test practices in a geriatric setting.
AB  - In assessing geriatric patients' functional status, health care professionals use
      a number of standardized tests. These tests have defined administration
      procedures that restrict communication and interaction with patients. In this
      article, we explore the experiences of occupational therapists and
      physiotherapists acting as standardized test administrators. Drawing on
      fieldwork, interviews with physiotherapists and occupational therapists, and
      observations of test situations on acute geriatric wards, we suggest that the
      test situation generates a tension between what standardization demands and what
      individualization requires. Our findings illustrate how physiotherapists and
      occupational therapists navigate between adherence to the test standard and
      meeting what they consider to be the individual patient's needs in the test
      situation. We problematize this navigation, and argue that the health care
      professional's use of relational competence is the means to reach and maintain
      individualization. 

PMID- 23863850
TI  - The nature of life-transforming changes among cancer survivors.
AB  - Some cancer survivors report positive subjective changes they describe as "life
      transforming." We used a grounded theory approach to identify the content,
      underlying process, and identifying characteristics of self-defined "life
      transforming" changes (LTCs) reported by 9 cancer survivors. To actualize their
      hopes for improvement, participants used a self-guided process centered on
      pragmatic action: researching options, gaining experience, and frankly evaluating
      results. Many participants discovered unanticipated personal abilities and
      resources, and those became highly useful in coping with other challenges apart
      from cancer. This made the increased personal abilities and resources "life
      transforming" rather than being substantially limited to reducing cancer-related
      problems. The action-oriented features and processes of LTCs seemed to be more
      fully described by experiential learning theory than by posttraumatic growth and
      coping. Supportive intervention to facilitate positive change processes could
      decrease suffering and enhance positive psychosocial and spiritual outcomes for
      cancer survivors. 

PMID- 23863854
TI  - Influence of geometric nanoparticle rotation on cellular internalization process.
AB  - It is increasingly recognized that the investigation of the rotational motion of
      geometric nanoparticles in the cellular internalization process is significant to
      understand certain fundamental cellular activities, such as endocytosis. However,
      the mechanism of rotation of geometric nanoparticles in the internalization
      process is still largely unknown. Here, we investigate the rotational dynamics of
      geometric nanoparticles when they adhere onto or are wrapped by lipid membranes,
      by using dissipative particle dynamics. A variety of rotational modes of the
      nanoparticles are observed, which are closely related to the complicated
      competition in the internalization process. We find that the breaking of
      geometric symmetry of a nanoparticle is important for the occurrence of particle
      rotation, while its effect can be changed by the orientation of the nanoparticles
      and the affinity between the ligands and the receptors. Importantly, it is found
      by our simulations that the rotational mode even determines the possible
      perturbation of the geometric nanoparticle to the membrane and the configuration
      between the nanoparticle and lipid membrane in the internalization process. These
      results provide a new strategy and also provide pivotal insight for the design of
      nanoparticles as advanced drug-delivery vectors to cells. 

PMID- 23863852
TI  - Hypoxia at the heart of sudden infant death syndrome?
AB  - Sudden infant death syndrome (SIDS) is a significant clinical problem without an
      accepted pathological mechanism, but with multiple conflicting models. Mutations
      in a growing number of genes have been found postmortem in SIDS cases, notably
      genes encoding ion channels. This can only account for a minority of cases,
      however. Our recent work on a novel mouse model of SIDS suggests a potentially
      more widespread role for cardiac arrhythmia in SIDS without needing to invoke the
      inheritance of abnormal ion-channel genes. We propose a model for SIDS
      pathogenesis whereby postnatal hypoxia leads to delayed maturation of the cardiac
      conduction system and an increased risk of cardiac arrhythmia. Our model may
      integrate several epidemiological findings related to risks factors for SIDS, and
      agrees with previous work suggesting a common final pathological pathway in SIDS.

PMID- 23863853
TI  - Kinetics of procalcitonin and C-reactive protein and the relationship to
      postoperative infection in young infants undergoing cardiovascular surgery.
AB  - BACKGROUND: The utility of procalcitonin (PCT) and C-reactive protein (CRP) as
      infectious biomarkers following infant cardiothoracic surgery is not well
      defined. METHODS: We designed a prospective cohort study to evaluate PCT and CRP
      after infant cardiothoracic surgery. PCT and CRP were drawn preoperatively and
      24/72 h postoperation or daily in delayed sternal closure patients. Presence of
      infection within 10 d of surgery, vasoactive-inotropic scores at 24 and 72 h, and
      length of intubation, intensive care unit stay, and hospital stay were
      documented. RESULTS: PCT and CRP were elevated at 24 h. PCT then decreased while
      CRP increased in patients undergoing delayed sternal closure or cardiopulmonary
      bypass. In the delayed sternal closure group, PCT was significantly higher on
      postoperative days 2-5 in patients who ultimately developed infection. Higher PCT
      was independently associated with increased vasoactive-inotropic score at 72 h.
      CRP did not correlate with infection or postoperative support. CONCLUSION: PCT
      rises after cardiothoracic surgery in infants but decreases by 72 h while CRP
      remains elevated. Sternal closure may affect CRP but not PCT. PCT is
      independently associated with circulatory support requirements at 72 h
      postoperation and with development of infection. PCT may have greater utility as
      a biomarker in this population.

PMID- 23863855
TI  - An early underwater artificial vision model in ocean investigations via
      independent component analysis.
AB  - Underwater vision is one of the dominant senses and has shown great prospects in
      ocean investigations. In this paper, a hierarchical Independent Component
      Analysis (ICA) framework has been established to explore and understand the
      functional roles of the higher order statistical structures towards the visual
      stimulus in the underwater artificial vision system. The model is inspired by
      characteristics such as the modality, the redundancy reduction, the sparseness
      and the independence in the early human vision system, which seems to
      respectively capture the Gabor-like basis functions, the shape contours or the
      complicated textures in the multiple layer implementations. The simulation
      results have shown good performance in the effectiveness and the consistence of
      the approach proposed for the underwater images collected by autonomous
      underwater vehicles (AUVs). 

PMID- 23863856
TI  - A new full pose measurement method for robot calibration.
AB  - Identification of robot kinematic errors during the calibration process often
      requires accurate full pose measurements (position and orientation) of robot end
      effectors in Cartesian space. This paper proposes a new method of full pose
      measurement of robot end-effectors for calibration. This method is based on an
      analysis of the features of a set of target points (placed on a rotating end
      effector) on a circular trajectory. The accurate measurement is validated by
      computational simulation results from the Puma robot. Moreover, experimental
      calibration and validation results for the Hyundai HA-06 robot prove the
      effectiveness, correctness, and reliability of the proposed method. This method
      can be applied to robots that have entirely revolute joints or to robots for
      which only the last joint is revolute. 

PMID- 23863857
TI  - Optimizing the thermal read-out technique for MIP-based biomimetic sensors:
      towards nanomolar detection limits.
AB  - In previous work, the novel heat-transfer method (HTM) for the detection of small
      molecules with Molecularly Imprinted Polymers (MIP)-type receptors was presented.
      In this study we focus on optimization of this sensor performance, with as final
      aim to lower the detection limit by reducing the noise level. It was determined
      that the noise originates foremost from the power supply, which can be controlled
      by varying the PID parameters. Therefore, the effect of the individual parameters
      was evaluated by tuning P, I and D separately at a temperature of 37  degrees C,
      giving a first indication of the optimal configuration. Next, a temperature
      profile was programmed and the standard deviation of the heat-transfer resistance
      over the entire regime was studied for a set of parameters. The optimal
      configuration, P1-I6-D0, reduced the noise level with nearly a factor of three
      compared to the original parameters of P10-I5-D0. With the optimized settings,
      the detection of L-nicotine in buffer solutions was studied and the detection
      limit improved significantly from 100 nM to 35 nM. Summarizing, optimization of
      the PID parameters and thereby improving the detection limit is a key parameter
      for first applications of the HTM-method for MIP receptors in analytical
      research. 

PMID- 23863858
TI  - Neutrophil interactions with the vascular endothelium.
AB  - Neutrophils are a key mediator of the innate immune system and are pivotal in the
      inflammatory response to infection or tissue damage. Fundamental to the role that
      neutrophils play in host defence is their interaction with the vascular
      endothelium. From the initial mobilisation of neutrophils out of the bone marrow
      to their ultimate transmigration through the vasculature, endothelial cells are a
      vital component of the inflammatory process. This review focuses on the
      interactions that take place between neutrophils and the vascular endothelium
      during the various stages of the inflammatory response. The role of the vascular
      endothelium in detecting the initial episode of infection or tissue damage is
      explored and how this ultimately leads to mobilisation of the neutrophils from
      the bone marrow and into the bloodstream. The recruitment and adhesion of
      neutrophils to the vascular endothelium is also discussed, with particular
      emphasis on the various discrete stages of the adhesion cascade and what
      molecules mediate these steps. In addition, a novel role for the lipid kinase
      sphingosine kinase in neutrophil adhesion is examined. With the advent of
      improved imaging techniques and the development of new animal models, this is a
      dynamic area of research and this review aims to summarise some of the more
      recent findings. 

PMID- 23863859
TI  - An exceptionally high boron content supramolecular cuboctahedron.
AB  - A boron-rich supramolecular cuboctahedron containing an impressive 240 boron
      atoms has been synthesized via coordination-driven assembly. The cuboctahedron,
      which is composed of Cu(2+) paddle-wheel nodes and carborane-isophthalic acids,
      was obtained simply and in high purity. The ability to precisely characterize the
      nanostructure via X-ray diffraction makes it unique among boron-rich
      nanostructures. 

PMID- 23863860
TI  - Environmentally friendly synthesis of highly hydrophobic and stable MIL-53 MOF
      nanomaterials.
AB  - The preparation of highly hydrophobic and stable MIL-53(Al) nanomaterials was
      achieved by an ionothermal synthesis strategy. The hydrophobicity of MIL-53(Al)it
      was studied by water adsorption; and the enhancement in this property was
      discussed with respect to its reference to MIL-53(Al)ht.

PMID- 23863861
TI  - Comorbidities and mortality in bipolar disorder: a Swedish national cohort study.
AB  - IMPORTANCE: Bipolar disorder is associated with premature mortality, but the
      specific causes and underlying pathways are unclear. OBJECTIVE: To examine the
      physical health effects of bipolar disorder using outpatient and inpatient data
      for a national population. DESIGN, SETTING, AND PARTICIPANTS: National cohort
      study of 6,587,036 Swedish adults, including 6618 with bipolar disorder. MAIN
      OUTCOMES AND MEASURES: Physical comorbidities diagnosed in any outpatient or
      inpatient setting nationwide and mortality (January 1, 2003, through December 31,
      2009). RESULTS: Women and men with bipolar disorder died 9.0 and 8.5 years
      earlier on average than the rest of the population, respectively. All-cause
      mortality was increased 2-fold among women (adjusted hazard ratio [aHR], 2.34;
      95% CI, 2.16-2.53) and men (aHR, 2.03; 95% CI, 1.85-2.23) with bipolar disorder,
      compared with the rest of the population. Patients with bipolar disorder had
      increased mortality from cardiovascular disease, diabetes mellitus, chronic
      obstructive pulmonary disease (COPD), influenza or pneumonia, unintentional
      injuries, and suicide for both women and men and cancer for women only. Suicide
      risk was 10-fold among women (aHR, 10.37; 95% CI, 7.36-14.60) and 8-fold among
      men (aHR, 8.09; 95% CI, 5.98-10.95) with bipolar disorder, compared with the rest
      of the population. Substance use disorders contributed only modestly to these
      findings. The association between bipolar disorder and mortality from chronic
      diseases (ischemic heart disease, diabetes, COPD, or cancer) was weaker among
      persons with a prior diagnosis of these conditions (aHR, 1.40; 95% CI, 1.26-1.56)
      than among those without a prior diagnosis (aHR, 2.38; 95% CI, 1.95-2.90;
      P(interaction) = .01). CONCLUSIONS AND RELEVANCE: In this large national cohort
      study, patients with bipolar disorder died prematurely from multiple causes,
      including cardiovascular disease, diabetes, COPD, influenza or pneumonia,
      unintentional injuries, and suicide. However, chronic disease mortality among
      those with more timely medical diagnosis approached that of the general
      population, suggesting that better provision of primary medical care may
      effectively reduce premature mortality among persons with bipolar disorder.

PMID- 23863862
TI  - Comparison of 1,4-distyrylfluorene and 1,4-distyrylbenzene analogues: synthesis,
      structure, electrochemistry and photophysics.
AB  - A series of nine 1,4-distyrylfluorene derivatives (2) functionalized with
      substituents of variable electrondonating or -accepting capabilities was
      synthesised. The photophysical properties of the molecules were investigated,
      including UV/vis absorption, photoluminescence emission, and fluorescence quantum
      yields. Photophysical properties of chromophores 2 were found to exhibit
      significant solvatochromic effects, especially in the Stokes shift and
      photoluminescence maxima. The electrochemical properties of series 2 were also
      assessed by cyclic voltammetry and differential pulse voltammetry. Results of
      photophysical and electrochemical analyses were further supported by DFT
      calculations (B3LYP/6-31G*) and single crystal X-ray diffraction on select
      molecules. The contributions of intermolecular pi-stacking and hydrogen bonding
      to crystal packing are discussed. A series of nine 1,4-distyrylphenylene
      derivatives (3) were also synthesised and similarly characterized for comparison
      to photophysical and solvatochromic effects observed in series 2. Properties of
      similarly-substituted molecules in series 2 and 3 were compared to one another in
      order to assess the influence of the 1,4-fluorenylene unit.

PMID- 23863863
TI  - Nuclear factor-kappaB pathway-activating gene aberrancies in primary cutaneous
      large B-cell lymphoma, leg type.

PMID- 23863864
TI  - Prevalent and rare mutations in IL-36RN gene in Chinese patients with generalized
      pustular psoriasis and psoriasis vulgaris.

PMID- 23863865
TI  - Influence of a priori Information, Designs, and Undetectable Data on Individual
      Parameters Estimation and Prediction of Hepatitis C Treatment Outcome.
AB  - Hepatitis C viral kinetic analysis based on nonlinear mixed effect models can be
      used to individualize treatment. For that purpose, it is necessary to obtain
      precise estimation of individual parameters. Here, we evaluated by simulation the
      influence on Bayesian individual parameter estimation and outcome prediction of a
      priori information on population parameters, viral load sampling designs, and
      methods for handling data below detection limit (BDL). We found that a precise
      estimation of both individual parameters and treatment outcome could be obtained
      using as few as six measurements in the first month of therapy. This result
      remained valid even when incorrect a priori information on population parameters
      was set as long as the parameters were identifiable and BDL data were properly
      handled. However, setting wrong values for a priori population parameters could
      lead to severe estimation/prediction errors if BDL data were ignored and not
      properly accounted in the likelihood function.CPT: Pharmacometrics & Systems
      Pharmacology (2013) 2, e56; doi:10.1038/psp.2013.31; published online 17 July
      2013. 

PMID- 23863866
TI  - Modeling and validating chronic pharmacological manipulation of circadian
      rhythms.
AB  - Circadian rhythms can be entrained by a light-dark (LD) cycle and can also be
      reset pharmacologically, for example, by the CK1delta/epsilon inhibitor PF
      670462. Here, we determine how these two independent signals affect circadian
      timekeeping from the molecular to the behavioral level. By developing a systems
      pharmacology model, we predict and experimentally validate that chronic
      CK1delta/epsilon inhibition during the earlier hours of a LD cycle can produce a
      constant stable delay of rhythm. However, chronic dosing later during the day, or
      in the presence of longer light intervals, is not predicted to yield an entrained
      rhythm. We also propose a simple method based on phase response curves (PRCs)
      that predicts the effects of a LD cycle and chronic dosing of a circadian drug.
      This work indicates that dosing timing and environmental signals must be
      carefully considered for accurate pharmacological manipulation of circadian
      phase.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e57;
      doi:10.1038/psp.2013.34; published online 17 July 2013. 

PMID- 23863867
TI  - The impact of lobular and ductal breast cancer histology on the metastatic
      behavior and long term survival of breast cancer patients.
AB  - The aim of the study was to evaluate the long-term survival of patients with
      invasive lobular carcinomas (ILC) and invasive ductal carcinomas (IDC) and the
      metastatic behavior of these two disease entities. Originally, all consecutive
      patients with pure lobular invasive breast cancers diagnosed between 1990 and
      1999 in the area served by the Tampere University Hospital and their matched IDC
      controls were identified and re-evaluated histopathologically in this follow-up
      study, resulting in a total of 243 ILCs and 243 IDCs. Data on recurrences and
      survival were collected until the end of year 2009. Statistical analyses
      including Kaplan-Meier method, log-rank test, Fisher's exact test and Cox
      regression analysis were performed with the PASW Statistics 18.0 computer
      program. P-values of <0.05 were considered statistically significant. Within the
      mean follow-up time of 10.04 years, locoregional recurrences were significantly
      more common among the ILCs than IDCs (35 vs. 20, p = 0.04), but no differences in
      the total number of distant recurrences or bilaterality were observed. However,
      when the first distant recurrence sites were studied, ILC patients had
      significantly less lung metastases (p = 0.04), but more skin metastases (p =
      0.04). During the whole follow-up period IDCs metastasized significantly more
      frequently to the lungs (p = 0.002), whereas gastrointestinal metastases were
      more common among ILCs (p = 0.02). Although the known favorable prognostic
      factors (hormone receptor positivity, low grade, low s-phase) were more common
      for the ILCs, the disease-free survival, the overall survival and the survival
      after recurrence did not differ between the groups. However, the Cox-regression
      model showed significantly worse survival for ILCs after adjusting for age, TNM
      status, grade and ER-positivity (p = 0.004). In conclusion, ILC and IDC differ in
      respect for visceral metastases. Despite the known favorable prognostic factors
      and originally favorable survival, patients with lobular histology appear to have
      a worse survival in the multivariate analysis after a prolonged follow-up. 

PMID- 23863868
TI  - Preparation, structural diversity and characterization of a family of Cd(II)
      organic frameworks.
AB  - Two Cd(II)-organic frameworks based on 5-iodoisophthalate (IIP(2-)),
      {[Cd(IIP)(bte)(H2O)].H2O}n (1) and [Cd(IIP)(bpp)(H2O)]n (2), were obtained either
      at an ambient temperature or under solvothermal conditions at 120  degrees C in
      the presence of 1,4-bis(1,2,4-triazol-1-yl)ethane (bte) and 1,3-bis(4
      pyridyl)propane (bpp) as auxiliary ligands, respectively. 1 is a novel discrete
      single-walled Cd(II)-organic tube (SWCOT) which further extends into a 3D
      supramolecular interdigitated microporous columnar architecture supported by C
      I...I halogen bonds and hydrogen bonds, while 2 exhibits an interesting two-fold
      interpenetrated 3D diamond network architecture. When the auxiliary ligands bte
      or bpp were replaced by a longer spacer ligand with more flexibility, 1,4
      bis(triazol-1-ylmethyl)benzene (bbtz), the unique discrete single-walled Cd(II)
      organic nanotube (SWCONT), {[Cd(IIP)(bbtz)(H2O)].H2O}n (3), which further extends
      into a 3D supramolecular microporous framework supported by face-to-face pi...pi
      stacking interactions and hydrogen bonds, was generated at room temperature.
      Under solvothermal conditions at 120  degrees C, an interesting two-fold 2D
      "embracing" (4,4) topological network, [Cd(IIP)(bbtz)(H2O)] (4), which further
      extends into a two-fold 3D "embracing" supramolecular framework through O-H...O
      hydrogen bonds, is obtained. 4 loses crystallinity in air, leading to the
      formation of [Cd(IIP)(bbtz)].0.5H2O (4A) evidenced by elemental analysis,
      thermogravimetric analysis (TGA) and powder X-ray diffraction (PXRD). Remarkably,
      in situ rapid and reversible dehydration-rehydration in static air occurs in 1-3,
      indicating their potential applications as water absorbent and sensing materials.
      Dehydrated 1 and 3 show selective gas adsorption of CO2 over N2 and dehydrated 3
      can adsorb methanol and ethanol vapors strongly. These compounds exhibit blue
      fluorescence in the solid state.

PMID- 23863869
TI  - Rotated domains in chemical vapor deposition-grown monolayer graphene on Cu(111):
      an angle-resolved photoemission study.
AB  - Copper is considered to be the most promising substrate for the growth of high
      quality and large area graphene by chemical vapor deposition (CVD), in
      particular, on the (111) facet. Because the interactions between graphene and Cu
      substrates influence the orientation, quality, and properties of the synthesized
      graphene, we studied the interactions using angle-resolved photoemission
      spectroscopy. The evolution of both the Shockley surface state of the Cu(111) and
      the pi band of the graphene was measured from the initial stage of CVD growth to
      the formation of a monolayer. Graphene growth was initiated along the Cu(111)
      lattice, where the Dirac band crossed the Fermi energy (EF) at the K point
      without hybridization with the d-band of Cu. Then two rotated domains were
      additionally grown as the area covered with graphene became wider. The Dirac
      energy was about -0.4 eV and the energy of the Shockley surface state of Cu(111)
      shifted toward the EF by ~0.15 eV upon graphene formation. These results indicate
      weak interactions between graphene and Cu, and that the electron transfer is
      limited to that between the Shockley surface state of Cu(111) and the pi band of
      graphene. This weak interaction and slight lattice mismatch between graphene and
      Cu resulted in the growth of rotated graphene domains (9.6 degrees  and 8.4
      degrees ), which showed no significant differences in the Dirac band with respect
      to different orientations. These rotated graphene domains resulted in grain
      boundaries which would hinder a large-sized single monolayer growth on Cu
      substrates.

PMID- 23863871
TI  - Impacts of natural hazards on primary health care facilities of iran: a 10-year
      retrospective survey.
AB  - Public health facilities in Iran are exposed to a wide range of natural hazards.
      This article presents the first survey of the impacts of such natural hazards on
      primary health care (PHC) centers in Iran from 2001 to 2011. A retrospective
      survey was conducted in 25 out of 30 provinces of Iran. Archival reports at
      provincial public health departments were cross-referenced with key informant
      interviews. During a 10-year period, 119 natural hazard events were recorded that
      led to physical damage and/or functional failure in 1,401 health centers, 127
      deaths and injury or illness in 644 health staff. Earthquakes accounted for the
      most physical damage and all health-worker deaths. However, there was an
      increasing trend of impacts due to hydro-meteorological hazards. Iran's health
      system needs to establish a registry to track the impact of natural hazards on
      health facilities, conduct regular hazard and vulnerability assessments and
      increase mitigation and preparedness measures. KEYWORDS: Disaster, primary health
      care, facility, Iran, natural hazard Corresponding author: Ali Ardalan MD, PhD.
      Iran's National Institute of Health Research, Tehran University of Medical
      Sciences. Harvard Humanitarian Initiative. Email: aardalan@tums.ac.ir.

PMID- 23863870
TI  - Genome-scale proteome quantification by DEEP SEQ mass spectrometry.
AB  - Advances in chemistry and massively parallel detection underlie DNA-sequencing
      platforms that are poised for application in personalized medicine. In stark
      contrast, systematic generation of protein-level data lags well behind genomics
      in virtually every aspect: depth of coverage, throughput, ease of sample
      preparation and experimental time. Here, to bridge this gap, we develop an
      approach based on simple detergent lysis and single-enzyme digest, extreme,
      orthogonal separation of peptides and true nanoflow liquid chromatography-tandem
      mass spectrometry that provides high peak capacity and ionization efficiency.
      This automated, deep efficient peptide sequencing and quantification mass
      spectrometry platform provides genome-scale proteome coverage equivalent to RNA
      seq ribosomal profiling and accurate quantification for multiplexed isotope
      labels. In a model of the embryonic to epiblast transition in murine stem cells,
      we unambiguously quantify 11,352 gene products that span 70% of Swiss-Prot and
      capture protein regulation across the full detectable range of high-throughput
      gene expression and protein translation. 

PMID- 23863872
TI  - A low-cost culture medium for the production of Nannochloropsis gaditana biomass
      optimized for aquaculture.
AB  - Nannochloropsis gaditana is a microalga with a high nutritional value and a
      protein and polyunsaturated fatty acid (PUFA) content that makes it interesting
      as a feed in aquaculture. To maximize its productivity and nutritional value in
      large-scale culture, a well-known commercial medium was optimized to the most
      favorable nutrient level using commercial fertilizers. Optimal growth conditions
      were obtained in the alternative fertilizer-based medium at a nitrogen
      concentration of 11.3 mM, a phosphorus concentration of 0.16 mM, and a
      micronutrient concentration of 30 MUL L(-1). This alternative medium allowed to
      obtain a biomass concentration similar to that achieved when using the commercial
      formula but with a reduction in Cu, Fe, and Mo content of 71%, 89%, and 99%,
      respectively. A maximum biomass productivity of 0.51 g L(-1) d(-1) was obtained.
      The eicosapentaenoic acid and protein contents of the biomass were 2.84% and 44%
      of dry weight, respectively.

PMID- 23863873
TI  - Enzyme-catalyzed synthesis of heptyl-beta-glycosides: effect of water coalescence
      at high temperature.
AB  - Alkyl glycosides can be synthesized by glycosidases in organic media with limited
      amounts of water. These systems, however, limit the solubility of the sugar
      substrates and decrease reaction yields. Herein we report the enzymatic synthesis
      of heptyl-beta-glycosides in heptanol catalyzed by a hyperthermophilic beta
      glycosidase at 90 degrees C. Our results indicate that dispersion of water in
      heptanol changes with time producing coalescence of water at the bottom of the
      reactor, playing a key role in the reaction yield. Water-soluble substrate,
      enzyme and products are concentrated in the aqueous phase, according to their
      partition coefficients, promoting side reactions that inactivate the enzyme.
      Reaction yield of heptyl-beta-glycosides was 35% relative to lactose, at 7%
      water. The increase in the water phase to 12% diminished the enzyme inactivation
      and increased the heptyl-beta-glycosides yield to 52%. Surface-active compounds,
      SDS and octyl glucoside, increased water dispersion but were unable to prevent
      coalescence. 

PMID- 23863874
TI  - Prevalence of Chlamydia trachomatis infection in the general population of women
      in Qatar.
AB  - OBJECTIVES: The Arabian Gulf region has limited epidemiological data related to
      sexually transmitted infections. The objective of this study was to estimate the
      prevalence of Chlamydia trachomatis infection among general population women in
      Doha, Qatar. METHODS: Endocervical swabs were collected from healthy women
      attending primary healthcare centres in Doha, June-December 2008. The specimens
      were tested for C trachomatis by a commercially available PCR-based assay. Data
      on basic socio-demographic characteristics, medical history and sexual behaviour
      were obtained using self-administered questionnaires. The prevalence of C
      trachomatis and of background variables were stratified by nationality, Qatari
      nationals versus non-Qatari residents. RESULTS: A total of 377 women were
      enrolled in the study, out of whom 351 (37.9% Qataris, 62.1% non-Qataris) were
      tested for the presence of C trachomatis in their specimens. The mean age of
      participants was 41.2 years, and the vast majority (93%, 95% CI 90.3 to 95.7)
      were married. The mean age at sexual debut was significantly lower among Qatari
      women compared with non-Qatari women (19.2 vs 22.2 years, respectively p<0.001),
      but the mean number of reported lifetime sexual partners (1.1 partner) was nearly
      the same in both groups (p=0.110). The prevalence of C trachomatis infection was
      5.3% among Qatari women and 5.5% among non-Qatari women, with no statistically
      significant difference between both groups (p=0.923). CONCLUSIONS: The prevalence
      of C trachomatis among women was higher than expected, with no significant
      difference between Qatari nationals and expatriate residents. The higher
      prevalence may reflect, in part, the limited access to and use of chlamydia
      screening and management.

PMID- 23863875
TI  - Pharmacological treatment of acute heart failure: current treatment and new
      targets.
AB  - Acute heart failure (AHF) is defined as the rapid onset of, or changes in, the
      symptoms and signs of heart failure (HF). It is a life-threatening situation in
      which diagnosis and initiation of therapy are crucial. The treatment aims are to
      stabilize the patient, improve clinical symptoms, and increase long-term survival
      rates. Few treatments have been investigated in clinical trials. This review
      summarizes the principles of pharmacologic treatment, the underlying clinical
      trials, and new pharmacologic targets.

PMID- 23863876
TI  - Conjunctive therapy of cisplatin with the OCT2 inhibitor cimetidine: influence on
      antitumor efficacy and systemic clearance.
AB  - The organic cation transporter 2 (OCT2) regulates uptake of cisplatin in proximal
      tubules, and inhibition of OCT2 protects against severe cisplatin-induced
      nephrotoxicity. However, it remains uncertain whether potent OCT2 inhibitors,
      such as cimetidine, can influence the antitumor properties and/or disposition of
      cisplatin. Using an array of preclinical assays, we found that cimetidine had no
      effect on the uptake and cytotoxicity of cisplatin in ovarian cancer cells with
      high OCT2 mRNA levels (IGROV-1 cells). Moreover, the antitumor efficacy of
      cisplatin in mice bearing luciferase-tagged IGROV-1 xenografts was unaffected by
      cimetidine (P = 0.39). Data obtained in 18 patients receiving cisplatin (100
      mg/m(2)) in a randomized crossover fashion with or without cimetidine (800 mg *
      2) revealed that cimetidine did not alter exposure to unbound cisplatin, a marker
      of antitumor efficacy (4.37 vs. 4.38 ug.h/ml; P = 0.86). These results support
      the future clinical exploration of OCT2 inhibitors as specific modifiers of
      cisplatin-induced nephrotoxicity.

PMID- 23863877
TI  - Association of CYP2C9*2 with bosentan-induced liver injury.
AB  - Bosentan (Tracleer) is an endothelin receptor antagonist prescribed for the
      treatment of pulmonary arterial hypertension (PAH). Its use is limited by drug
      induced liver injury (DILI). To identify genetic markers of DILI, association
      analyses were performed on 56 Caucasian PAH patients receiving bosentan. Twelve
      functional polymorphisms in five genes (ABCB11, ABCC2, CYP2C9, SLCO1B1, and
      SLCO1B3) implicated in bosentan pharmacokinetics were tested for associations
      with alanine aminotransferase (ALT), aspartate aminotransferase (AST), and DILI.
      After adjusting for body mass index, CYP2C9*2 was the only polymorphism
      associated with ALT, AST, and DILI (beta = 2.16, P = 0.024; beta = 1.92, P =
      0.016; odds ratio 95% CI = 2.29-infinity, P = 0.003, respectively). Bosentan
      metabolism by CYP2C9*2 in vitro was significantly reduced compared with CYP2C9*1
      and was comparable to that by CYP2C9*3. These results suggest that CYP2C9*2 is a
      potential genetic marker for prediction of bosentan-induced liver injury and
      warrants investigation for the optimization of bosentan treatment. 

PMID- 23863880
TI  - Direct N-cyclopropylation of secondary acyclic amides promoted by copper.
AB  - The N-cyclopropylation of aromatic and aliphatic secondary acyclic amides, known
      to be poor nucleophiles, has been accomplished using a simple and cheap copper
      system. The corresponding tertiary acyclic amides, which constitute a wide family
      of biologically active compounds, have been obtained in good to excellent yields.

PMID- 23863879
TI  - Posttranslational modifications of HIV-1 integrase by various cellular proteins
      during viral replication.
AB  - HIV-1 integrase (IN) is a key viral enzyme during HIV-1 replication that
      catalyzes the insertion of viral DNA into the host genome. Recent studies have
      provided important insights into the multiple posttranslational modifications
      (PTMs) of IN (e.g., ubiquitination, SUMOylation, acetylation and
      phosphorylation), which regulate its multifaceted functions. A number of host
      cellular proteins, including Lens Epithelium-derived Growth factor (LEDGF/p75),
      p300 and Ku70 have been shown to interact with IN and be involved in the PTM
      process of IN, either facilitating or counteracting the IN PTMs. Although
      previous studies have revealed much about the important roles of IN PTMs, how IN
      functions are fine-tuned by these PTMs under the physiological setting still
      needs to be determined. Here, we review the advances in the understanding of the
      mechanisms and roles of multiple IN PTMs.

PMID- 23863878
TI  - Chromatin dynamics during lytic infection with herpes simplex virus 1.
AB  - Latent HSV-1 genomes are chromatinized with silencing marks. Since 2004, however,
      there has been an apparent inconsistency in the studies of the chromatinization
      of the HSV-1 genomes in lytically infected cells. Nuclease protection and
      chromatin immunoprecipitation assays suggested that the genomes were not
      regularly chromatinized, having only low histone occupancy. However, the
      chromatin modifications associated with transcribed and non-transcribed HSV-1
      genes were those associated with active or repressed transcription, respectively.
      Moreover, the three critical HSV-1 transcriptional activators all had the
      capability to induce chromatin remodelling, and interacted with critical
      chromatin modifying enzymes. Depletion or overexpression of some, but not all,
      chromatin modifying proteins affected HSV-1 transcription, but often in
      unexpected manners. Since 2010, it has become clear that both cellular and HSV-1
      chromatins are highly dynamic in infected cells. These dynamics reconcile the
      weak interactions between HSV-1 genomes and chromatin proteins, detected by
      nuclease protection and chromatin immunoprecipitation, with the proposed
      regulation of HSV-1 gene expression by chromatin, supported by the marks in the
      chromatin in the viral genomes and the abilities of the HSV-1 transcription
      activators to modulate chromatin. It also explains the sometimes unexpected
      results of interventions to modulate chromatin remodelling activities in infected
      cells. 

PMID- 23863882
TI  - Donor bone marrow-derived dendritic cells prolong corneal allograft survival and
      promote an intragraft immunoregulatory milieu.
AB  - Investigations into cell therapies for application in organ transplantation have
      grown. Here, we describe the ex vivo generation of donor bone marrow-derived
      dendritic cells (BMDCs) and glucocorticoid-treated BMDCs with potent
      immunomodulatory properties for application in allogeneic transplantation. BMDCs
      were treated with dexamethasone (Dexa) to induce an immature, maturation
      resistant phenotype. BMDC and Dexa BMDC phenotype, antigen presenting cell
      function, and immunomodulatory properties were fully characterized. Both
      populations display significant immunomodulatory properties, including, but not
      limited to, a significant increase in mRNA expression of programmed death-ligand
      1 and indoleamine 2,3-dioxygenase. BMDCs and Dexa BMDCs display a profound
      impaired capacity to stimulate allogeneic lymphocytes. Moreover, in a fully MHC
      I/II mismatched rat corneal transplantation model, injection of donor-derived,
      untreated BMDC or Dexa BMDCs (1 * 10(6) cells, day -7) significantly prolonged
      corneal allograft survival without the need for additional immunosuppression.
      Although neovascularization was not reduced and evidence of donor-specific
      alloantibody response was detected, a significant reduction in allograft cellular
      infiltration combined with a significant increase in the ratio of intragraft
      FoxP3-expressing regulatory cells was observed. Our comprehensive analysis
      demonstrates the novel cellular therapeutic approach and significant effect of
      donor-derived, untreated BMDCs and Dexa BMDCs in preventing corneal allograft
      rejection.

PMID- 23863883
TI  - Clouston syndrome with heterozygous GJB6 mutation p.Ala88Val and GJB2 variant
      p.Val27Ile revealing mild sensorineural hearing loss and photophobia.

PMID- 23863884
TI  - Abstracts of the 2013 Annual Meeting of the International Anesthesia Research
      Society. San Diego, California, USA. May 4-7, 2013.

PMID- 23863881
TI  - No impact of lentiviral transduction on hematopoietic stem/progenitor cell
      telomere length or gene expression in the rhesus macaque model.
AB  - The occurrence of clonal perturbations and leukemia in patients transplanted with
      gamma-retroviral (RV) vector-transduced autologous hematopoietic stem and
      progenitor cells (HSPCs) has stimulated extensive investigation, demonstrating
      that proviral insertions may perturb adjacent proto-oncogene expression. Although
      enhancer-deleted lentiviruses are less likely to result in insertional
      oncogenesis, there is evidence that they may perturb transcript splicing, and one
      patient with a benign clonal expansion of lentivirally transduced HPSC has been
      reported. The rhesus macaque model provides an opportunity for informative long
      term analysis to ask whether transduction impacts on long-term HSPC properties.
      We used two techniques to examine whether lentivirally transduced HSPCs from
      eight rhesus macaques transplanted 1-13.5 years previously are perturbed at a
      population level, comparing telomere length as a measure of replicative history
      and gene expression profile of vector positive versus vector negative cells.
      There were no differences in telomere lengths between sorted GFP+ and GFP- blood
      cells, suggesting that lentiviral (LV) transduction did not globally disrupt
      replicative patterns. Bone marrow GFP+ and GF- CD34+ cells showed no differences
      in gene expression using unsupervised and principal component analysis. These
      studies did not uncover any global long-term perturbation of proliferation,
      differentiation, or other important functional parameters of transduced HSPCs in
      the rhesus macaque model.

PMID- 23863885
TI  - Diverse reactivity in microwave-promoted catalyst-free coupling of substituted
      anilines with ethyl trifluoropyruvate and biological evaluation.
AB  - Diverse reactivity by coupling of substituted anilines with ethyl
      trifluoropyruvate was developed under microwave irradiation without catalysts to
      generate 3-trifluoromethyl-3-hydroxy oxindoles, aromatic hydroxy trifluoromethyl
      esters, and 1,2-dicarbonyl compounds in a fast and efficient manner. The
      plausible mechanism for obtaining different products was proposed. Furthermore,
      the anti-HIV activity of aromatic hydroxy trifluoromethyl esters was first
      reported. The best inhibitory activity against wild-type HIV-1 IIIB was
      exemplified by trifluoromethyloxindole 3q with an IC50 = 5.8 MUM, which also
      displayed potential activity against Y181C mutant virus with an IC50 = 7.5 MUM.
      More significantly, the activities of oxindoles 3q and 3r to inhibit K103N/Y181C
      double mutant HIV-1 reverse transcriptase (RT) are probably similar to that of
      the second-generation nonnucleoside inhibitor HBY 097 by docking calculation.

PMID- 23863886
TI  - Synthesis, spectral and redox switchable cubic NLO properties of chiral dinuclear
      iron cyanide/isocyanide-bridged complexes.
AB  - Two chiral dinuclear cyanide/isocyanide-bridged complexes (R)-[Cp(dppe)Fe-CN
      Fe(dppp)Cp]PF6 (1[PF6]) and (R)-[Cp(dppe)Fe-NC-Fe(dppp)Cp]PF6 (2[PF6]), and their
      mono-oxidation products (R)-[Cp(dppe)Fe(II)-CN-Fe(III)(dppp)Cp] [PF6]2 (1[PF6]2)
      and (R)-[Cp(dppe)Fe(III)-NC-Fe(II)(dppp)Cp][PF6]2 (2[PF6]2) were synthesized and
      fully characterized. The electronic spectra of both the mixed-valence complexes
      1[PF6]2 and 2[PF6]2 exhibit a strong and broad absorption band with two
      discernable peaks in the NIR region, which are attributed to Fe(II)-Fe(III) IVCT
      transitions. The attributions are supported by the DFT calculations. Under
      irradiation with a nanosecond laser at 1064 nm, the measured third-order NLO
      results of all four cyanide-bridged complexes showed that complexes 1(+) and 2(+)
      do not exhibit an NLO response, but their one-electron oxidation complexes 1(2+)
      and 2(2+) exhibit a strong NLO response due to a resonance enhanced effect. In
      addition, both complexes 1(2+) and 2(2+) display RSA and self-defocusing effects
      and show good optical limiting behavior in a broadband range.

PMID- 23863887
TI  - From knowledge to action in public health management: experiences from a
      Norwegian context.
AB  - AIMS: A pro-active approach that incorporates the effective use of scientific
      evidence and data is a major goal in public health work. This study aimed to
      identify local and regional strengths and barriers to identify, translate, and
      use relevant evidence of "what works" in public health management. METHODS: Focus
      group discussions were performed among 22 researchers, public health leaders
      and/or leaders with organisational and policy responsibilities in two
      municipalities, one county, and a university research centre. RESULTS: Access to
      the population's health data is insufficient for taking action. The focus group
      discussions clarified a need for a skills programme that specifically focuses on
      analysis and process expertise. Moreover, communication and collaboration among
      key stakeholders involved in evidence-based practices like research, policy, and
      practice should be enhanced in order to facilitate evidence-based policy making.
      CONCLUSIONS: The complex relationship between context and behaviour and the
      necessity of influencing systems and structures as well as individuals to promote
      change underlines the need for a clear national initiative to facilitate
      knowledge exchanges among practitioners, policy makers, and researchers.

PMID- 23863888
TI  - Perceived gender inequality in the couple relationship and musculoskeletal pain
      in middle-aged women and men.
AB  - AIMS: Musculoskeletal pain is a major health problem, especially in women, and is
      partially determined by psychosocial factors. The aim of the present study was to
      investigate whether gender inequality in the couple relationship was related to
      musculoskeletal pain. METHODS: Participants (n=721; 364 women and 357 men) were
      all individuals living in a couple relationship in the Northern Swedish Cohort, a
      26-year Swedish cohort study. Self-administered questionnaire data at age 42
      years comprised perceived gender inequality in the couple relationship and
      musculoskeletal pain (in three locations, summarised into one score and median
      split), concurrent demographic factors, psychological distress, and previous
      musculoskeletal pain at age 30 years. Associations were examined using logistic
      regression. RESULTS: Gender inequality was positively associated with symptoms of
      musculoskeletal pain in the total sample, remaining significant after addition of
      possible confounders and of previous musculoskeletal pain. Separate adjustment
      for concurrent psychological distress attenuated the association but not below
      significance. The association was present and of comparable strength in both
      women and men. CONCLUSIONS: Gender inequality in the couple relationship might
      contribute to the experience of musculoskeletal pain in both women and men. The
      results highlight the potential adverse bodily consequences of living in unequal
      relationships.

PMID- 23863889
TI  - Detection of DNA induced gold nanoparticle aggregation with dark field imaging.
AB  - Dark field imaging was employed to visualize and quantify complementary DNA
      induced gold nanoparticle aggregation at the single-particle level, with a
      detection limit of 100 fM DNA, which allows the highly sensitive detection of
      single nucleotide polymorphisms (SNPs). Results suggested that the aggregation
      process is consistent with the cluster-cluster model. 

PMID- 23863890
TI  - Antiferromagnetic FeSe monolayer on SrTiO3: the charge doping and electric field
      effects.
AB  - By growing monolayer FeSe on SrTiO3(001) surface, researchers obtain the highest
      superconducting transition-temperature for iron-based superconductor. Here, we
      study the antiferromagnetic (AFM) checkerboard monolayer FeSe adsorbed on
      SrTiO3(001) surface. We show that the system has a considerable charge transfer
      from SrTiO3(001) substrate to FeSe monolayer, and so has a self-constructed
      electric field. The FeSe monolayer band structure near the Brillouin zone (BZ)
      center is sensitive to charge doping, and the spin-resolved energy bands at BZ
      corner are distorted to be flattened by the perpendicular electric field. It is
      revealed that the striking disappearance of the Fermi surface around the BZ
      center can be well explained by the AFM checkerboard phase with charge doping and
      electric field effects. We propose a tight-binding model Hamiltonian to take
      these key factors into account. We also show that this composite structure is an
      ideal electron-hole bilayer system, with electrons and holes respectively formed
      in FeSe monolayer and TiO2 surface layer. 

PMID- 23863891
TI  - Meta-arylation of calixarenes using organomercurial chemistry.
AB  - A direct mercuration reaction combined with a subsequent Pd-catalyzed arylation
      was used to introduce the aryl moiety into the meta position of the calix[4]arene
      skeleton. The application of organomercurial intermediates thus allows the
      straightforward formation of meta-aryl-substituted derivatives representing a
      unique substitution pattern in calixarene chemistry. 

PMID- 23863892
TI  - Effectiveness of national implementation of prolonged exposure therapy in
      Veterans Affairs care.
AB  - IMPORTANCE: Posttraumatic stress disorder (PTSD) is a pervasive and often
      debilitating condition that affects many individuals in the general population
      and military service members. Effective treatments for PTSD are greatly needed
      for both veterans returning from Iraq and Afghanistan and veterans of other eras.
      Prolonged exposure (PE) therapy has been shown to be highly efficacious in
      clinical trials involving women with noncombat trauma, but there are limited data
      on its effectiveness in real-world clinical practice settings and with veterans.
      OBJECTIVE: To evaluate the effectiveness of PE as implemented with veterans with
      PTSD in a large health care system. DESIGN, SETTING, AND PARTICIPANTS: This
      evaluation included 1931 veterans treated by 804 clinicians participating in the
      Department of Veterans Affairs (VA) PE Training Program. After completing a 4-day
      experiential PE training workshop, clinicians implemented PE (while receiving
      consultation) with a minimum of 2 veteran patients who had a primary diagnosis of
      PTSD. MAIN OUTCOMES AND MEASURES: Changes in PTSD and depression symptoms were
      assessed with the PTSD Checklist and the Beck Depression Inventory II, measured
      at baseline and at the final treatment session. Multiple and single imputation
      were used to estimate the posttest scores of patients who left treatment before
      completing 8 sessions. Demographic predictors of treatment dropout were also
      examined. RESULTS: Intent-to-treat analyses indicate that PE is effective in
      reducing symptoms of both PTSD (pre-post d = 0.87) and depression (pre-post d =
      0.66), with effect sizes comparable to those reported in previous efficacy
      trials. The proportion of patients screening positive for PTSD on the PTSD
      Checklist decreased from 87.6% to 46.2%. CONCLUSIONS: Clinically significant
      reductions in PTSD symptoms were achieved among male and female veterans of all
      war eras and veterans with combat-related and non-combat-related PTSD. Results
      also indicate that PE is effective in reducing depression symptoms, even though
      depression is not a direct target of the treatment.

PMID- 23863894
TI  - Reconstructing genome evolution in historic samples of the Irish potato famine
      pathogen.
AB  - Responsible for the Irish potato famine of 1845-49, the oomycete pathogen
      Phytophthora infestans caused persistent, devastating outbreaks of potato late
      blight across Europe in the 19th century. Despite continued interest in the
      history and spread of the pathogen, the genome of the famine-era strain remains
      entirely unknown. Here we characterize temporal genomic changes in introduced P.
      infestans. We shotgun sequence five 19th-century European strains from archival
      herbarium samples--including the oldest known European specimen, collected in
      1845 from the first reported source of introduction. We then compare their
      genomes to those of extant isolates. We report multiple distinct genotypes in
      historical Europe and a suite of infection-related genes different from modern
      strains. At virulence-related loci, several now-ubiquitous genotypes were absent
      from the historical gene pool. At least one of these genotypes encodes a virulent
      phenotype in modern strains, which helps explain the 20th century's episodic
      replacements of European P. infestans lineages.

PMID- 23863896
TI  - Mouse extraembryonic arterial vessels harbor precursors capable of maturing into
      definitive HSCs.
AB  - During mouse development, definitive hematopoietic stem cells (dHSCs) emerge by
      late E10.5 to E11 in several hematopoietic sites. Of them, the aorta-gonad
      mesonephros (AGM) region drew particular attention owing to its capacity to
      autonomously initiate and expand dHSCs in culture, indicating its key role in HSC
      development. The dorsal aorta contains characteristic hematopoietic clusters and
      is the initial site of dHSC emergence, where they mature through vascular
      endothelial (VE)-cadherin(+)CD45(-)CD41(low) (type 1 pre-HSCs) and VE
      cadherin(+)CD45(+) (type 2 pre-HSCs) intermediates. Although dHSCs were also
      found in other embryonic niches (placenta, yolk sac, and extraembryonic vessels),
      attempts to detect their HSC initiating potential have been unsuccessful to date.
      Extraembryonic arterial vessels contain hematopoietic clusters, suggesting that
      they develop HSCs, but functional evidence for this has been lacking. Here we
      show that umbilical cord and vitelline arteries (VAs), but not veins, contain pre
      HSCs capable of maturing into dHSCs in the presence of exogenous interleukin 3,
      although in fewer numbers than the AGM region, and that pre-HSC activity in VAs
      increases with proximity to the embryo proper. Our functional data strongly
      suggest that extraembryonic arteries can actively contribute to adult
      hematopoiesis. 

PMID- 23863895
TI  - JAK2V617F expression in mice amplifies early hematopoietic cells and gives them a
      competitive advantage that is hampered by IFNalpha.
AB  - The acquired gain-of-function V617F mutation in the Janus Kinase 2 (JAK2(V617F))
      is the main mutation involved in BCR/ABL-negative myeloproliferative neoplasms
      (MPNs), but its effect on hematopoietic stem cells as a driver of disease
      emergence has been questioned. Therefore, we reinvestigated the role of
      endogenous expression of JAK2(V617F) on early steps of hematopoiesis as well as
      the effect of interferon-alpha (IFNalpha), which may target the JAK2(V617F) clone
      in humans by using knock-in mice with conditional expression of JAK2(V617F) in
      hematopoietic cells. These mice develop a MPN mimicking polycythemia vera with
      large amplification of myeloid mature and precursor cells, displaying erythroid
      endogenous growth and progressing to myelofibrosis. Interestingly, early
      hematopoietic compartments [Lin-, LSK, and SLAM (LSK/CD48-/CD150+)] increased
      with the age. Competitive repopulation assays demonstrated disease appearance and
      progressive overgrowth of myeloid, Lin-, LSK, and SLAM cells, but not
      lymphocytes, from a low number of engrafted JAK2(V617F) SLAM cells. Finally,
      IFNalpha treatment prevented disease development by specifically inhibiting
      JAK2(V617F) cells at an early stage of differentiation and eradicating disease
      initiating cells. This study shows that JAK2(V617F) in mice amplifies not only
      late but also early hematopoietic cells, giving them a proliferative advantage
      through high cell cycling and low apoptosis that may sustain MPN emergence but is
      lost upon IFNalpha treatment. 

PMID- 23863897
TI  - Insulin-like growth factor-1 receptor (IGF1R) as a novel target in chronic
      lymphocytic leukemia.
AB  - The receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R)
      is implicated in various tumor entities including chronic lymphocytic leukemia
      (CLL), but its functional significance in this disease remains poorly
      characterized. Here, we show that the IGF1R protein is overexpressed in various
      CLL subsets, suggesting a contribution to CLL pathology. Indeed, we show that
      IGF1R knockdown in primary human CLL cells compromised their viability. Likewise,
      IGF1R inhibition with 3 structurally distinct compounds induced apoptosis, even
      in the presence of protective stroma components. Furthermore, IGF1R inhibition
      effectively limited CLL development in EMU-TCL1 transgenic mice and of primary
      human CLL xenografts. In agreement with its prosurvival function, IGF1R
      inhibition affected the phosphorylation and/or expression of multiple signaling
      proteins. The multikinase inhibitor sorafenib yielded similar effects on these
      signaling elements as IGF1R inhibitors. Indeed, IGF1R appears to be a direct
      sorafenib target because sorafenib decreased IGF1R expression and
      phosphorylation, counteracted insulin-like growth factor-1 (IGF-1) binding to CLL
      cells, and lowered the in vitro kinase activity of recombinant, purified IGF1R.
      Thus, we demonstrate that blockade of IGF1R-mediated signaling represents a novel
      mechanism of action for sorafenib in CLL. Importantly, IGF1R inhibitors
      compromise CLL viability in their microenvironment context, implicating this RTK
      as a promising therapeutic target. 

PMID- 23863893
TI  - Evaluation of eligibility criteria in living donor liver transplantation for
      hepatocellular carcinoma by alpha-SMA-positive cancer-associated fibroblasts.
AB  - The eligibility criteria of liver transplantation (LT) for hepatocellular
      carcinoma (HCC) must clearly confirm the prognosis not only from pathological
      diagnosis but also from pre-operative imaging diagnosis. In the present study, we
      evaluated published eligibility criteria for LT based on both pre-operative
      imaging diagnosis and pathological diagnosis using living donor liver
      transplantation (LDLT) recipients at our hospital by alpha-smooth muscle actin
      (SMA)-positive cancer-associated fibroblasts (CAFs) in HCC. The Up-to-seven (Up
      to-7), Asan and Tokyo criteria were evaluated, in both overall survival and HCC
      disease-free survival, to be statistically significantly beneficial criteria to
      define post-LDLT prognosis. Recipients only within Up-to-7 criteria based on both
      pre-operative imaging diagnosis and pathological diagnosis survived without HCC
      recurrence. Recipients with proliferation of alpha-SMA-positive CAFs in HCC had
      significantly poorer prognosis. All survival recipients without HCC recurrence,
      who were above the Up-to-7 criteria in pathological diagnosis, had no
      proliferation of alpha-SMA-positive CAFs. As a result of multivariate analysis,
      the significant independent factors defining prognosis of recipients after LDLT
      for HCC were Up-to-7 criteria and proliferation of alpha-SMA-positive CAFs. The
      ideal eligibility criteria for LDLT with HCC is Up-to-7 criteria and alpha-SMA
      positive CAFs was considered to be an important factor in HCC recurrence. LDLT
      should be limited to recipients within Up-to-7 criteria or without proliferation
      of alpha-SMA-positive CAFs.

PMID- 23863898
TI  - The value of allogeneic and autologous hematopoietic stem cell transplantation in
      prognostically favorable acute myeloid leukemia with double mutant CEBPA.
AB  - The clinical value of allogeneic hematopoietic stem cell transplantation
      (alloHSCT) and autologous hematopoietic stem cell transplantation (autoHSCT) in
      the subtype of acute myeloid leukemia (AML) with double mutant CEBPA (CEBPAdm)
      has remained unsettled. Among 2983 patients analyzed for CEBPA mutational status
      (age 18-60 years) treated on 4 published Dutch-Belgian-Swiss Hemato-Oncology
      Cooperative Group (HOVON/SAKK) and 3 German-Austrian AML Study Group (AMLSG)
      protocols (2 published, 1 registered, clinicaltrials.gov NCT00151255), 124 had
      AML with CEBPAdm and achieved first complete remission (CR1). Evaluation of the
      clinical impact of alloHSCT and autoHSCT vs chemotherapy was performed by
      addressing time dependency in the statistical analyses. Thirty-two patients
      proceeded to alloHSCT from a matched related (MRD, n = 29) or a matched unrelated
      donor (MUD, n = 3), 20 to autoHSCT in CR1 and 72 received chemotherapy. Relapse
      free survival was significantly superior in patients receiving an alloHSCT or
      autoHSCT in CR1 as compared with chemotherapy (P < .001), whereas overall
      survival was not different (P < .12). Forty-five patients relapsed. Of 42
      patients treated with reinduction therapy, 35 achieved a second CR (83%) and most
      patients (n = 33) received an alloHSCT MRD, n = 11; MUD, n = 19; haplo-identical
      donor, n = 3). Survival of relapsed patients measured from date of relapse was
      46% after 3 years. Adult AML patients with CEBPAdm benefit from alloHSCT and
      autoHSCT; relapsed patients still have a favorable outcome after reinduction
      followed by alloHSCT. 

PMID- 23863899
TI  - Implications of continued response after autologous stem cell transplantation for
      multiple myeloma.
AB  - Patients undergoing autologous stem cell transplantation (ASCT) for multiple
      myeloma (MM) undergo disease assessment approximately 100 days later. Some
      patients continue to have a decline in their serum or urine monoclonal protein
      after day 100 in the absence of additional therapy. We evaluated 430 MM patients
      who underwent ASCT within 12 months of their diagnosis and had not achieved a
      complete remission at day 100. Of these patients, 167 (39%) had a continued
      response after day 100 without additional therapy. When compared with patients
      who did not (n = 263), those who had a continued response had a longer
      progression-free survival (35 vs 13 months, P < .001), time to next therapy (43
      vs 16 months, P < .001), and overall survival (96 vs 57 months, P < .001). This
      phenomenon of a continued response maintained prognostic value in a multivariable
      analysis and should be considered when interpreting posttransplant responses. 

PMID- 23863901
TI  - Differential regulation of TLR-dependent MyD88 and TRIF signaling pathways by
      free zinc ions.
AB  - Zinc signals are utilized by several immune cell receptors. One is TLR4, which
      causes an increase of free zinc ions (Zn(2+)) that is required for the MyD88
      dependent expression of inflammatory cytokines. This study investigates the role
      of Zn(2+) on Toll/IL-1R domain-containing adapter inducing IFN-beta (TRIF)
      dependent signals, the other major intracellular pathway activated by TLR4.
      Chelation of Zn(2+) with the membrane-permeable chelator N,N,N',N'-Tetrakis(2
      pyridylmethyl)ethylenediamine augmented TLR4-mediated production of IFN-beta and
      subsequent synthesis of inducible NO synthase and production of NO. The effect is
      based on Zn(2+) acting as a negative regulator of the TRIF pathway via reducing
      IFN regulatory factor 3 activation. This was also observed with TLR3, the only
      TLR that signals exclusively via TRIF, but not MyD88, and does not trigger a zinc
      signal. In contrast, IFN-gamma-induced NO production was unaffected by N,N,N',N'
      Tetrakis(2-pyridylmethyl)ethylenediamine. Taken together, Zn(2+) is specifically
      involved in TLR signaling, where it differentially regulates MyD88 and TRIF
      signaling via a zinc signal or via basal Zn(2+) levels, respectively. 

PMID- 23863900
TI  - Neddylation plays an important role in the regulation of murine and human
      dendritic cell function.
AB  - Posttranslational protein modifications (PTMs) are necessary for cells to
      function properly. The role of PTMs in regulating immune responses, specifically
      those mediated by dendritic cells (DCs), which are critical for both innate and
      adaptive immunity, is not well understood. Utilizing multiple but complementary
      approaches, we determined the role of an important but less understood type of
      PTM, namely, neddylation, in regulating DC functions. Inhibition of neddylation
      suppressed the release of proinflammatory cytokines by DCs in response to Toll
      like receptor, nucleotide oligomerization domain-like receptor, and noninfectious
      CD40L stimulation. These effects were more profound than those mediated by the
      proteasome inhibitor bortezomib or a commonly used antiinflammatory agent,
      dexamethasone. Targeting neddylation also suppressed the ability of DCs to
      stimulate murine allogeneic T cells in vitro and in vivo and human allogeneic T
      cell responses in vitro. Mechanistic studies demonstrated that inhibition of
      neddylation reduced both canonical and noncanonical nuclear factor-kappaB (NF
      kappaB) activity. Neddylation inhibition prevented the degradation of inhibitor
      kappaB and thus reduced the translocation and activation of NF-kappaB, but
      without perturbation of the mitogen-activated protein kinase/extracellular signal
      regulated kinase pathway. Thus, blocking neddylation could be a novel strategy
      for mitigating immune-mediated disease processes.

PMID- 23863905
TI  - Prototypic long pentraxin PTX3 is present in breast milk, spreads in tissues, and
      protects neonate mice from Pseudomonas aeruginosa lung infection.
AB  - Newborns and infants present a higher susceptibility to infection than adults, a
      vulnerability associated with deficiencies in both the innate and adaptive immune
      systems. Innate immune receptors are sensors involved in the recognition and
      elimination of microbes that play a pivotal role at the interface between innate
      and adaptive immunity. Pentraxin 3 (PTX3), the prototypic long pentraxin, is a
      soluble pattern recognition receptor involved in the initiation of protective
      responses against selected pathogens. Because neonates are generally resistant to
      these pathogens, we suspected that PTX3 may be provided by a maternal source
      during the early life times. We observed that human colostrum contains high
      levels of PTX3, and that mammary epithelial cell and CD11b(+) milk cells
      constitutively produce PTX3. Interestingly, PTX3 given orally to neonate mice was
      rapidly distributed in different organs, and PTX3 ingested during lactation was
      detected in neonates. Finally, we observed that orally administered PTX3 provided
      protection against Pseudomonas aeruginosa lung infection in neonate mice.
      Therefore, breastfeeding constitutes, during the early life times, an important
      source of PTX3, which actively participates in the protection of neonates against
      infections. In addition, these results suggest that PTX3 might represent a
      therapeutic tool for treating neonatal infections and support the view that
      breastfeeding has beneficial effects on the neonates' health. 

PMID- 23863904
TI  - IL-17 receptor A signaling is protective in infection-stimulated periapical bone
      destruction.
AB  - IL-17 is a pleiotropic cytokine produced by Th17 T cells that induces a myriad of
      proinflammatory mediators. However, different models of inflammation report
      opposite functional roles of IL-17 signal in terms of its effects on bone
      destruction. In this study we determined the role of IL-17RA signal in bone
      resorption stimulated by dentoalveolar infections. Infrabony resorptive lesions
      were induced by surgical pulp exposure and microbial infection of mouse molar
      teeth. IL-17 was strongly induced in periapical tissues in wild-type (WT) mice by
      7 d after the infection but was not expressed in uninfected mice. Dentoalveolar
      infections of IL-17RA knockout (KO) mice demonstrated significantly increased
      bone destruction and more abscess formation in the apical area compared with WT
      mice. Infected IL-17RA KO mice exhibited significantly increased neutrophils and
      macrophages compared with the WT littermates at day 21, suggesting a failure of
      transition from acute to chronic inflammation in the IL-17RA KO mice. The
      expression of IL-1 (both alpha and beta isoforms) and MIP2 were significantly
      upregulated in the IL-17RA KO compared with WT mice at day 21 postinfection. The
      development of periapical lesions in IL-17RA KO mice was significantly attenuated
      by neutralization of IL-1beta and MIP2. Taken together, these results demonstrate
      that IL-17RA signal seems to be protective against infection-induced periapical
      inflammation and bone destruction via suppression of neutrophil and mononuclear
      inflammation. 

PMID- 23863902
TI  - VP2 dominated CD4+ T cell responses against enterovirus 71 and cross-reactivity
      against coxsackievirus A16 and polioviruses in a healthy population.
AB  - Enterovirus 71 (EV71)-associated hand-foot-mouth disease has become a major
      threat to public health in the Asia-Pacific region. Although T cell immunity is
      closely correlated with clinical outcomes of EV71 infection, little is known
      about T cell immunity baseline against EV71 and T cell immunogenecity of EV71 Ags
      in the population, which has restricted our understanding of immunoprotection
      mechanisms. In this study, we investigated the cellular immune responses against
      the four structural Ags of EV71 and determined the immunohierarchy of these Ags
      in healthy adults. A low frequency of EV71-responsive T cells was detected
      circulating in peripheral blood, and broad T cell immune responses could be
      identified in most of the subjects after in vitro expansion. We demonstrated that
      the VP2 Ag with broad distribution of immunogenic peptides dominates T cell
      responses against EV71 compared with VP1, VP3, and VP4. Furthermore, the
      responses were illuminated to be mainly single IFN-gamma-secreting CD4(+) T cell
      dependent, indicating the previous natural acute viral infection of the adult
      population. Conservancy analysis of the immunogenic peptides revealed that
      moderately variant peptides were in the majority in coxsackievirus A16 (CV-A16)
      whereas most of the peptides were highly variant in polioviruses. Less efficient
      cross-reactivity against CV-A16 might broadly exist among individuals, whereas
      influences derived from poliovirus vaccination would be limited. Our findings
      suggest that the significance of VP2 Ag should be addressed in the future EV71
      responsive immunological investigations. And the findings concerning the less
      efficient cross-reactivity against CV-A16 and limited influences from poliovirus
      vaccination in EV71-contacted population would contribute to a better
      understanding of immunoprotection mechanisms against enteroviruses. 

PMID- 23863906
TI  - Staphylococcal Ecb protein and host complement regulator factor H enhance
      functions of each other in bacterial immune evasion.
AB  - Staphylococcus aureus is a major human pathogen causing more than a tenth of all
      septicemia cases and often superficial and deep infections in various tissues.
      One of the immune evasion strategies of S. aureus is to secrete proteins that
      bind to the central complement opsonin C3b. One of these, extracellular
      complement binding protein (Ecb), is known to interfere directly with functions
      of C3b. Because C3b is also the target of the physiological plasma complement
      regulator, factor H (FH), we studied the effect of Ecb on the complement
      regulatory functions of FH. We show that Ecb enhances acquisition of FH from
      serum onto staphylococcal surfaces. Ecb and FH enhance mutual binding to C3b and
      also the function of each other in downregulating complement activation. Both Ecb
      and the C-terminal domains 19-20 of FH bind to the C3d part of C3b. We show that
      the mutual enhancing effect of Ecb and FH on binding to C3b depends on binding of
      the FH domain 19 to the C3d part of C3b next to the binding site of Ecb on C3d.
      Our results show that Ecb, FH, and C3b form a tripartite complex. Upon exposure
      of serum-sensitive Haemophilus influenzae to human serum, Ecb protected the
      bacteria, and this effect was enhanced by the addition of the C-terminal domains
      19-20 of FH. This finding indicates that the tripartite complex formation could
      give additional protection to bacteria and that S. aureus is thereby able to use
      host FH and bacterial Ecb in a concerted action to eliminate C3b at the site of
      infection. 

PMID- 23863903
TI  - ERAAP and tapasin independently edit the amino and carboxyl termini of MHC class
      I peptides.
AB  - Effective CD8(+) T cell responses depend on presentation of a stable peptide
      repertoire by MHC class I (MHC I) molecules on the cell surface. The overall
      quality of peptide-MHC I complexes (pMHC I) is determined by poorly understood
      mechanisms that generate and load peptides with appropriate consensus motifs onto
      MHC I. In this article, we show that both tapasin (Tpn), a key component of the
      peptide loading complex, and the endoplasmic reticulum aminopeptidase associated
      with Ag processing (ERAAP) are quintessential editors of distinct structural
      features of the peptide repertoire. We carried out reciprocal immunization of
      wild-type mice with cells from Tpn- or ERAAP-deficient mice. Specificity analysis
      of T cell responses showed that absence of Tpn or ERAAP independently altered the
      peptide repertoire by causing loss as well as gain of new pMHC I. Changes in
      amino acid sequences of MHC-bound peptides revealed that ERAAP and Tpn,
      respectively, defined the characteristic amino and carboxy termini of canonical
      MHC I peptides. Thus, the optimal pMHC I repertoire is produced by two distinct
      peptide editing steps in the endoplasmic reticulum. 

PMID- 23863907
TI  - An ultrasensitive biosensor for DNA detection based on hybridization chain
      reaction coupled with the efficient quenching of a ruthenium complex to CdTe
      quantum dots.
AB  - A highly sensitive and selective DNA biosensor based on hybridization chain
      reaction is described, which combines CdTe quantum dots (QDs) and a ruthenium
      complex. Based on the variation of fluorescence signals of the CdTe QDs, the
      target DNA is determined. 

PMID- 23863909
TI  - Cellular and humoral immune responses in type 1 diabetic patients participating
      in a phase III GAD-alum intervention trial.
AB  - OBJECTIVE: GAD formulated in aluminum hydroxide (GAD-alum) has previously been
      shown to induce preservation of residual insulin secretion in recent-onset type 1
      diabetes, but recent phase II and III GAD-alum trials failed to reach primary
      outcomes. The European phase III study was therefore closed after 15 months, and
      only a minority of patients completed the 30 months of follow-up. RESEARCH DESIGN
      AND METHODS: This study aimed to characterize cellular and humoral responses in
      the Swedish patients (n = 148) participating in the phase III trial, receiving
      four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD65 antibody (GADA)
      levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative
      responses in peripheral blood mononuclear cells (PBMCs) were analyzed. RESULTS:
      The GAD65-induced cytokine profile tended to switch toward a predominant Th2
      associated profile over time both in the 2D and 4D group. The groups also
      displayed increased GADA levels and PBMC proliferation compared with placebo,
      whereas GADA IgG subclass distribution changed in 4D patients. CONCLUSIONS: Both
      2D and 4D patients displayed GAD65-specifc cellular and humoral effects after GAD
      alum treatment, but at different time points and magnitudes. No specific immune
      markers could be associated with treatment efficacy.

PMID- 23863908
TI  - Feasibility and effectiveness in clinical practice of a multifactorial
      intervention for the reduction of cardiovascular risk in patients with type 2
      diabetes: the 2-year interim analysis of the MIND.IT study: a cluster randomized
      trial.
AB  - OBJECTIVE: To evaluate the feasibility and effectiveness of an intensive,
      multifactorial cardiovascular risk reduction intervention in a clinic-based
      setting. RESEARCH DESIGN AND METHODS: The study was a pragmatic, cluster
      randomized trial, with the diabetes clinic as the unit of randomization. Clinics
      were randomly assigned to either continue their usual care (n = 5) or to apply an
      intensive intervention aimed at the optimal control of cardiovascular disease
      (CVD) risk factors and hyperglycemia (n = 4). To account for clustering, mixed
      model regression techniques were used to compare differences in CVD risk factors
      and HbA1c. Analyses were performed both by intent to treat and as treated per
      protocol. RESULTS: Nine clinics completed the study; 1,461 patients with type 2
      diabetes and no previous cardiovascular events were enrolled. After 2 years,
      participants in the interventional group had significantly lower BMI, HbA1c, LDL
      cholesterol, and triglyceride levels and significantly higher HDL cholesterol
      level than did the usual care group. The proportion of patients reaching the
      treatment goals was systematically higher in the interventional clinics (35% vs.
      24% for LDL cholesterol, P = 0.1299; 93% vs. 82% for HDL cholesterol, P = 0.0005;
      80% vs. 64% for triglycerides, P = 0.0002; 39% vs. 22% for HbA1c, P = 0.0259; 13%
      vs. 5% for blood pressure, P = 0.1638). The analysis as treated per protocol
      confirmed these findings, showing larger and always significant differences
      between the study arms for all targets. CONCLUSIONS: A multifactorial intensive
      intervention in type 2 diabetes is feasible and effective in clinical practice
      and it is associated with significant and durable improvement in HbA1c and CVD
      risk profile.

PMID- 23863910
TI  - Plasma copeptin and renal outcomes in patients with type 2 diabetes and
      albuminuria.
AB  - OBJECTIVE: Plasma copeptin, a surrogate for vasopressin, was associated with
      albuminuria in population-based studies. These associations are consistent with
      the effect of vasopressin on albuminuria observed in humans and rodents. The
      objective of this study was to determine whether plasma copeptin is an
      independent marker of risk of renal events in people with type 2 diabetes and
      albuminuria. RESEARCH DESIGN AND METHODS: We studied 3,101 participants of the
      DIABHYCAR trial (6-year follow-up) with type 2 diabetes and albuminuria. A renal
      event was defined as doubling of serum creatinine or development of end-stage
      renal disease. RESULTS: During follow-up, 86 renal events occurred in 76 subjects
      (2.45%). Incidences by tertiles of baseline plasma copeptin were 1.06% (T1),
      1.45% (T2), and 4.84% (T3). They were 2.43% (T1), 5.11% (T2), and 11.81% (T3) for
      the subset of subjects with macroalbuminuria at baseline (n = 729). Hazard ratio
      for plasma copeptin tertiles as a risk for renal events was 4.79 (95% CI, 2.48
      9.24; P < 0.0001; for T3 vs. T1). In a stepwise regression analysis, urinary
      albumin excretion and plasma copeptin remained positively associated and HDL
      cholesterol and estimated glomerular filtration rate were inversely associated
      with the incidence of renal events. These independent predictors explained ~18%
      of the variance of the outcome. The yearly variations of estimated glomerular
      filtration rate by copeptin tertiles were -1.43 +/- 0.51 (T1), -2.29 +/- 0.49
      (T2), and -3.52 +/- 0.44 mL/min/1.73 m2 per year (T3) (P = 0.005) in subjects
      with macroalbuminuria. CONCLUSIONS: Plasma copeptin may help to identify subjects
      with diabetic chronic kidney disease who are at high risk for renal function
      decline.

PMID- 23863911
TI  - Resiliency theory: a strengths-based approach to research and practice for
      adolescent health.

PMID- 23863913
TI  - Low temperature red luminescence of a fluorinated Mn-doped zinc selenite.
AB  - M2(SeO3)F2 (M = Zn (1), Mn (2)) stoichiometric phases together with the Zn2
      xMnx(SeO3)F2 compound doped at various concentrations (x = 0.002-0.2) were
      synthesized by employing mild hydrothermal conditions. These compounds have been
      characterized by scanning electron microscopy (SEM), Rietveld refinement of the X
      ray powder diffraction patterns, ICP-Q-MS, thermogravimetric and
      thermodiffractometric analyses, and IR, UV/vis and electron paramagnetic
      resonance (EPR) spectroscopies. Compounds 1 and 2 crystallize in the orthorhombic
      Pnma space group with lattice parameters: a = 7.27903(4), b = 10.05232(6) and c =
      5.26954(3) A for the zinc species and a = 7.50848(9), b = 10.3501(12) and c =
      5.47697(6) A for the manganese phase, with Z = 4. The crystal structures of these
      compounds are isotypic and are built up from a 3D framework constructed by (010)
      sheets of [MO3F3] octahedra linked up by [SeO3] building units. Luminescence
      measurements of Mn2(SeO3)F2 were performed at different temperatures between 10
      and 150 K. At 10 K, the emission spectrum consists of a broad band peaked at
      around 660 nm related to the (4)T1g->(6)A1g transition in octahedrically
      coordinated Mn(2+). Moreover, the influence of temperatures up to 295 K and the
      Mn concentration on the luminescent properties of the Zn2-xMnx(SeO3)F2 system
      were systematically studied. Magnetic measurements of 2 show antiferromagnetic
      coupling as the major interactions exhibiting a spin canting at low temperature. 

PMID- 23863912
TI  - A prediction model for the incidence of civil detention for crisis patients with
      psychiatric illnesses; the Amsterdam study of acute psychiatry VII.
AB  - OBJECTIVE: Given raised numbers of civil detentions in the Netherlands and other
      European countries, it is important to assess the patient risk profile with
      respect to the incidence of those far-reaching treatment decisions. The aim of
      the ASAP study is to develop a comprehensive prediction model that considers all
      possible patient-related predictors known from earlier research. METHODS: We took
      a random sample of 252 from the 2,682 patients coming into contact with two
      psychiatric emergency teams in Amsterdam between September 2004 and September
      2006. We recorded socio-demographic and clinical characteristics, aspects of
      social support and psychiatric history. We interviewed the patients using the
      Verona Service Satisfaction Scale (Verona-EU) and the Birchwood Insight Scale.
      During a two-year follow-up period we noted their use of mental health care
      facilities. RESULTS: Stepwise logistic regression analyses with resulted in a
      final prediction model (P <= 0.001) including preceding involuntary admission (OR
      9.4, 95% CI 3.6-24.7, P <= 0.001), domestic situation alone (OR 4.5, 95% CI 1.9
      11.0, P = 0.001) and VSSS score satisfactory (OR 0.2, 95% CI 0.0-0.8, P = 0.030)
      as predictors of civil detention during 2 years of follow-up. CONCLUSION: With
      the presented prediction model it will be possible to identify patients at a high
      risk of civil detention: patients with a history of previous involuntary
      admissions who live alone and are not satisfied with the mental health care they
      got before. This suggests the possibility that timely preventive measures can be
      taken comprising the adjustment or intensification of the treatment plan for this
      specific group of patients.

PMID- 23863914
TI  - Umbilicated facial papules in an immunosuppressed patient.

PMID- 23863915
TI  - A dual location stimuli-responsive degradation strategy of block copolymer
      nanocarriers for accelerated release.
AB  - A new strategy that centers on the incorporation of stimuli-responsive cleavable
      linkages in dual or multiple locations as in both micellar cores and at
      polymer/solution interfaces leading to synergistically enhanced release of
      encapsulated anticancer drugs in cancer cells. 

PMID- 23863916
TI  - Biphasic catalysis using amphiphilic polyphenols-chelated noble metals as highly
      active and selective catalysts.
AB  - In the field of catalysis, it is highly desired to develop novel catalysts that
      combine the advantages of both homogeneous and heterogeneous catalysts. Here we
      disclose that the use of plant polyphenol as amphiphilic large molecule
      ligand/stabilizer allows for the preparation of noble metal complex and noble
      metal nanoparticle catalysts. These catalysts are found to be highly selective
      and active in aqueous-organic biphasic catalysis of cinnamaldehyde and quinoline,
      and can be reused at least 3 times without significant loss of activity.
      Moreover, the catalytic activity and reusability of the catalysts can be
      rationally controlled by simply adjusting the content of polyphenols in the
      catalysts. Our strategy may be extended to design a wide range of aqueous-organic
      biphasic catalysis system.

PMID- 23863917
TI  - Brinzolamide/brimonidine (Simbrinza) for glaucoma.

PMID- 23863918
TI  - Citalopram, escitalopram, and the QT interval.

PMID- 23863919
TI  - Crofelemer (Fulyzaq) for antiretroviral-induced diarrhea.

PMID- 23863920
TI  - Cytochalasin B induces apoptosis through the mitochondrial apoptotic pathway in
      HeLa human cervical carcinoma cells.
AB  - Cytochalasin B (CB) is a cell-permeable mycotoxin. It inhibits cytoplasmic
      division by blocking the formation of contractile microfilaments, it inhibits
      cell movement and induces nuclear extrusion. In the present study, we
      investigated the anticancer activity of CB in HeLa human cervical carcinoma
      cells. CB showed significant cytotoxicity, with an IC50 of 7.9 uM, in a WST-8
      assay and significantly inhibited cell proliferation. Furthermore, results from
      Annexin V-FITC/propidium iodide double-staining indicated that CB induced early
      apoptosis of HeLa cells in a time-dependent manner. The cells exhibited apoptotic
      morphology, including cell shrinkage and nuclear condensation. CB induced cell
      cycle arrest at the S phase. We also observed inhibition of DNA replication in a
      [3H]-thymidine incorporation assay. Furthermore, CB induced a time-dependent
      increase in reactive oxygen species and a decrease in mitochondrial membrane
      potential. Western blot analysis showed an increase in levels of mitochondrial
      factors Bax and Bcl-2, which was followed by activation of caspase-9 and -3.
      These results suggested that CB induced apoptosis via a mitochondrial-dependent
      pathway in HeLa cells.

PMID- 23863923
TI  - Captodiamine, a putative antidepressant, enhances hypothalamic BDNF expression in
      vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism.
AB  - The putative antidepressant captodiamine is a 5-HT2c receptor antagonist and
      agonist at sigma-1 and D3 dopamine receptors, exerts an anti-immobility action in
      the forced swim paradigm, and enhances dopamine turnover in the frontal cortex.
      Captodiamine has also been found to ameliorate stress-induced anhedonia, reduce
      the associated elevations of hypothalamic corticotrophin-releasing factor (CRF)
      and restore the reductions in hypothalamic BDNF expression. Here we demonstrate
      chronic administration of captodiamine to have no significant effect on
      hypothalamic CRF expression through sigma-1 receptor agonism; however, both sigma
      1 receptor agonism or 5-HT2c receptor antagonism were necessary to enhance BDNF
      expression. Regulation of BDNF expression by captodiamine was associated with
      increased phosphorylation of transcription factor CREB and mediated through sigma
      1 receptor agonism but blocked by 5-HT2c receptor antagonism. The existence of
      two separate signalling pathways was confirmed by immunolocalisation of each
      receptor to distinct cell populations in the paraventricular nucleus of the
      hypothalamus. Increased BDNF induced by captodiamine was also associated with
      enhanced expression of synapsin, but not PSD-95, suggesting induction of long
      term structural plasticity between hypothalamic synapses. These unique features
      of captodiamine may contribute to its ability to ameliorate stress-induced
      anhedonia as the hypothalamus plays a prominent role in regulating HPA axis
      activity. 

PMID- 23863924
TI  - A systematic review of the effects of NMDA receptor antagonists on oscillatory
      activity recorded in vivo.
AB  - Distinct frequency bands can be differentiated from neuronal ensemble recordings,
      such as local field potentials or electrocorticogram recordings. Recent years
      have witnessed a rapid acceleration of research examining how N-methyl-D
      aspartate receptor (NMDAR) antagonists influence fundamental frequency bands in
      cortical and subcortical brain regions. Herein, we systematically review findings
      from in vivo studies with a focus on delta, theta, gamma and more recently
      identified high-frequency oscillations. We also discuss some of the current
      hypotheses that are considered to account for the actions of NMDAR antagonists on
      these frequency bands. The data emphasize a close relationship between altered
      oscillatory activity and NMDAR blockade, with both local and large-scale networks
      accounting for their effects. These findings may have fundamental implications
      for the psychotomimetic effects produced by NMDAR antagonists. 

PMID- 23863925
TI  - Electroconvulsive seizure-induced changes in gene expression in the mouse
      hypothalamic paraventricular nucleus.
AB  - Electroconvulsive therapy is an effective and rapid treatment for depression. In
      patients with depression, the function of the paraventricular nucleus of the
      hypothalamus (PVN) is frequently altered. Electroconvulsive seizure (ECS), which
      is a model of electroconvulsive therapy, upregulates the expression of c-fos in
      the PVN of animal models. Therefore, we hypothesized that ECS alters gene
      expression and function in the PVN. The PVN was microdissected from mouse brain
      sections following ECS treatment, and total RNA was analyzed by microarray. Two
      hours after ECS, the levels of expression of 2.6% (589 genes) of the genes showed
      a greater than 2-fold decrease and 0.9% (205 genes) showed a greater than 2-fold
      increase. Among these genes, 72 of the downregulated genes and 12 of the
      upregulated genes have been proposed to be associated with psychiatric disorders,
      such as depression, by knowledge database analyses. The groups of downregulated
      genes included neuropeptides (Cck), kinases (Prkcb, Camk2a), transcription
      factors (Tcf4), and transporters (Aqp4), and these have been suggested to be
      associated with psychiatric disorders and/or PVN function. The results of the
      present study indicated that ECS treatment could modulate PVN functions through
      altered gene expression, which may contribute to its antidepressant effects. 

PMID- 23863926
TI  - Neonatal MK-801 treatment differentially alters the effect of adolescent or adult
      MK-801 challenge on locomotion and PPI in male and female rats.
AB  - Schizophrenia is a neurodevelopmental disorder and is typically "triggered" by
      subsequent insults in life. The N-methyl-D-aspartate (NMDA) receptor antagonist
      dizocilpine (MK-801) induces locomotor hyperactivity and prepulse inhibition
      (PPI) deficits, which can mimic the schizophrenia phenotype. In this experiment,
      we assessed whether neonatal exposure to MK-801 (postnatal days 5-14) could
      induce sensitization to both hyperactivity and PPI deficit caused by later-life
      acute MK-801 treatment during adolescence or adulthood. Our results showed that
      the hyperactivity induced by an acute MK-801 challenge was enhanced in male and
      female rats after neonatal MK-801 treatment. Notably, in the PPI test, adult
      female rats neonatally exposed to MK-801 exhibited a significantly greater
      reduction in PPI in response to acute MK-801 administration, whereas male rats
      receiving neonatal MK-801 treatment expressed attenuated PPI disruption in
      adulthood. Our data indicate that a combination of neonatal and later-life NMDA
      receptor blockades could induce sensitization in the locomotor activity of both
      sexes in adolescence and adulthood. In addition, a sex difference was observed in
      the effects of this treatment regime on PPI. 

PMID- 23863928
TI  - Alleviation of high light-induced photoinhibition in cyanobacteria by
      artificially conferred biosilica shells.
AB  - Bioinspired by diatoms, biomimetic silicification confers an artificial shell on
      cyanobacteria to alleviate photoinhibition; thus, the photosynthesis of the
      resulting cyanobacteria@SiO2 becomes more efficient under high light conditions. 

PMID- 23863927
TI  - Therapeutics targeting angiogenesis: genetics and epigenetics, extracellular
      miRNAs and signaling networks (Review).
AB  - Angiogenesis is a process of neovascular formation from pre-existing blood
      vessels, which consists of sequential steps for vascular destabilization,
      angiogenic sprouting, lumen formation and vascular stabilization. Vascular
      endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiopoietin,
      Notch, transforming growth factor-beta (TGF-beta), Hedgehog and WNT signaling
      cascades orchestrate angiogenesis through the direct or indirect regulation of
      quiescence, migration and the proliferation of endothelial cells. Small-molecule
      compounds and human/humanized monoclonal antibodies interrupting VEGF signaling
      have been developed as anti-angiogenic therapeutics for cancer and neovascular
      age-related macular degeneration (AMD). Gene or protein therapy delivering VEGF,
      FGF2 or FGF4, as well as cell therapy using endothelial progenitor cells (EPCs),
      mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been
      developed as pro-angiogenic therapeutics for ischemic heart disease and
      peripheral vascular disease. Anti-angiogenic therapy for cancer and neovascular
      AMD is more successful than pro-angiogenic therapy for cardiovascular diseases,
      as VEGF-signal interruption is technically feasible compared with vascular re
      construction. Common and rare genetic variants are detected using array-based
      technology and personal genome sequencing, respectively. Drug and dosage should
      be determined based on personal genotypes of VEGF and other genes involved in
      angiogenesis. As epigenetic alterations give rise to human diseases, polymer
      based hydrogel film may be utilized for the delivery of drugs targeting
      epigenetic processes and angiogenesis as treatment modalities for cardiovascular
      diseases. Circulating microRNAs (miRNAs) in exosomes and microvesicles are
      applied as functional biomarkers for diagnostics and prognostics, while synthetic
      miRNAs in polymer-based nanoparticles are applicable for therapeutics. A more
      profound understanding of the spatio-temporal interactions of regulatory
      signaling cascades and advances in personal genotyping and miRNA profiling are
      required for the optimization of targeted therapy.

PMID- 23863929
TI  - Influenza: Pathways to human adaptation.

PMID- 23863930
TI  - Heavy solitons in a fermionic superfluid.
AB  - Solitons-solitary waves that maintain their shape as they propagate-occur as
      water waves in narrow canals, as light pulses in optical fibres and as quantum
      mechanical matter waves in superfluids and superconductors. Their highly
      nonlinear and localized nature makes them very sensitive probes of the medium in
      which they propagate. Here we create long-lived solitons in a strongly
      interacting superfluid of fermionic atoms and directly observe their motion. As
      the interactions are tuned from the regime of Bose-Einstein condensation of
      tightly bound molecules towards the Bardeen-Cooper-Schrieffer limit of long-range
      Cooper pairs, the solitons' effective mass increases markedly, to more than 200
      times their bare mass, signalling strong quantum fluctuations. This mass
      enhancement is more than 50 times larger than the theoretically predicted value.
      Our work provides a benchmark for theories of non-equilibrium dynamics of
      strongly interacting fermions. 

PMID- 23863931
TI  - Stretchable nanoparticle conductors with self-organized conductive pathways.
AB  - Research in stretchable conductors is fuelled by diverse technological needs.
      Flexible electronics, neuroprosthetic and cardiostimulating implants, soft
      robotics and other curvilinear systems require materials with high conductivity
      over a tensile strain of 100 per cent (refs 1-3). Furthermore, implantable
      devices or stretchable displays need materials with conductivities a thousand
      times higher while retaining a strain of 100 per cent. However, the molecular
      mechanisms that operate during material deformation and stiffening make
      stretchability and conductivity fundamentally difficult properties to combine.
      The macroscale stretching of solids elongates chemical bonds, leading to the
      reduced overlap and delocalization of electronic orbitals. This conductivity
      stretchability dilemma can be exemplified by liquid metals, in which conduction
      pathways are retained on large deformation but weak interatomic bonds lead to
      compromised strength. The best-known stretchable conductors use polymer matrices
      containing percolated networks of high-aspect-ratio nanometre-scale tubes or
      nanowires to address this dilemma to some extent. Further improvements have been
      achieved by using fillers (the conductive component) with increased aspect ratio,
      of all-metallic composition, or with specific alignment (the way the fillers are
      arranged in the matrix). However, the synthesis and separation of high-aspect
      ratio fillers is challenging, stiffness increases with the volume content of
      metallic filler, and anisotropy increases with alignment. Pre-strained
      substrates, buckled microwires and three-dimensional microfluidic polymer
      networks have also been explored. Here we demonstrate stretchable conductors of
      polyurethane containing spherical nanoparticles deposited by either layer-by
      layer assembly or vacuum-assisted flocculation. High conductivity and
      stretchability were observed in both composites despite the minimal aspect ratio
      of the nanoparticles. These materials also demonstrate the electronic tunability
      of mechanical properties, which arise from the dynamic self-organization of the
      nanoparticles under stress. A modified percolation theory incorporating the self
      assembly behaviour of nanoparticles gave an excellent match with the experimental
      data.

PMID- 23863932
TI  - The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of
      autophagy.
AB  - Autophagy is an evolutionarily conserved catabolic process involved in several
      physiological and pathological processes. Although primarily cytoprotective,
      autophagy can also contribute to cell death; it is thus important to understand
      what distinguishes the life or death decision in autophagic cells. Here we report
      that induction of autophagy is coupled to reduction of histone H4 lysine 16
      acetylation (H4K16ac) through downregulation of the histone acetyltransferase
      hMOF (also called KAT8 or MYST1), and demonstrate that this histone modification
      regulates the outcome of autophagy. At a genome-wide level, we find that H4K16
      deacetylation is associated predominantly with the downregulation of autophagy
      related genes. Antagonizing H4K16ac downregulation upon autophagy induction
      results in the promotion of cell death. Our findings establish that alteration in
      a specific histone post-translational modification during autophagy affects the
      transcriptional regulation of autophagy-related genes and initiates a regulatory
      feedback loop, which serves as a key determinant of survival versus death
      responses upon autophagy induction. 

PMID- 23863934
TI  - Structural biology: meet the B family.

PMID- 23863933
TI  - Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates
      eicosanoids.
AB  - Phosphorylated sphingolipids ceramide-1-phosphate (C1P) and sphingosine-1
      phosphate (S1P) have emerged as key regulators of cell growth, survival,
      migration and inflammation. C1P produced by ceramide kinase is an activator of
      group IVA cytosolic phospholipase A2alpha (cPLA2alpha), the rate-limiting
      releaser of arachidonic acid used for pro-inflammatory eicosanoid production,
      which contributes to disease pathogenesis in asthma or airway hyper
      responsiveness, cancer, atherosclerosis and thrombosis. To modulate eicosanoid
      action and avoid the damaging effects of chronic inflammation, cells require
      efficient targeting, trafficking and presentation of C1P to specific cellular
      sites. Vesicular trafficking is likely but non-vesicular mechanisms for C1P
      sensing, transfer and presentation remain unexplored. Moreover, the molecular
      basis for selective recognition and binding among signalling lipids with
      phosphate headgroups, namely C1P, phosphatidic acid or their lyso-derivatives,
      remains unclear. Here, a ubiquitously expressed lipid transfer protein, human
      GLTPD1, named here CPTP, is shown to specifically transfer C1P between membranes.
      Crystal structures establish C1P binding through a novel surface-localized,
      phosphate headgroup recognition centre connected to an interior hydrophobic
      pocket that adaptively expands to ensheath differing-length lipid chains using a
      cleft-like gating mechanism. The two-layer, alpha-helically-dominated 'sandwich'
      topology identifies CPTP as the prototype for a new glycolipid transfer protein
      fold subfamily. CPTP resides in the cell cytosol but associates with the trans
      Golgi network, nucleus and plasma membrane. RNA interference-induced CPTP
      depletion elevates C1P steady-state levels and alters Golgi cisternae stack
      morphology. The resulting C1P decrease in plasma membranes and increase in the
      Golgi complex stimulates cPLA2alpha release of arachidonic acid, triggering pro
      inflammatory eicosanoid generation. 

PMID- 23863935
TI  - Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle.
AB  - Despite the large size of the Xenopus laevis egg (approximately 1.2 mm diameter),
      a fertilized egg rapidly proceeds through mitosis in a spatially coordinated
      fashion. Mitosis is initiated by a bistable system of regulatory proteins centred
      on Cdk1 (refs 1, 2), raising the possibility that this spatial coordination could
      be achieved through trigger waves of Cdk1 activity. Using an extract system that
      performs cell cycles in vitro, here we show that mitosis does spread through
      Xenopus cytoplasm via trigger waves, propagating at a linear speed of
      approximately 60 um min(-1). Perturbing the feedback loops that give rise to the
      bistability of Cdk1 changes the speed and dynamics of the waves. Time-lapse
      imaging of intact eggs argues that trigger waves of Cdk1 activation are
      responsible for surface contraction waves, ripples in the cell cortex that
      precede cytokinesis. These findings indicate that Cdk1 trigger waves help ensure
      the spatiotemporal coordination of mitosis in large eggs. Trigger waves may be an
      important general mechanism for coordinating biochemical events over large
      distances. 

PMID- 23863938
TI  - Condensed-matter physics: Dark and heavy.

PMID- 23863937
TI  - Structure of the human glucagon class B G-protein-coupled receptor.
AB  - Binding of the glucagon peptide to the glucagon receptor (GCGR) triggers the
      release of glucose from the liver during fasting; thus GCGR plays an important
      role in glucose homeostasis. Here we report the crystal structure of the seven
      transmembrane helical domain of human GCGR at 3.4 A resolution, complemented by
      extensive site-specific mutagenesis, and a hybrid model of glucagon bound to GCGR
      to understand the molecular recognition of the receptor for its native ligand.
      Beyond the shared seven transmembrane fold, the GCGR transmembrane domain
      deviates from class A G-protein-coupled receptors with a large ligand-binding
      pocket and the first transmembrane helix having a 'stalk' region that extends
      three alpha-helical turns above the plane of the membrane. The stalk positions
      the extracellular domain (~12 kilodaltons) relative to the membrane to form the
      glucagon-binding site that captures the peptide and facilitates the insertion of
      glucagon's amino terminus into the seven transmembrane domain.

PMID- 23863936
TI  - Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem
      cell quiescence.
AB  - The epigenetic regulation of imprinted genes by monoallelic DNA methylation of
      either maternal or paternal alleles is critical for embryonic growth and
      development. Imprinted genes were recently shown to be expressed in mammalian
      adult stem cells to support self-renewal of neural and lung stem cells; however,
      a role for imprinting per se in adult stem cells remains elusive. Here we show
      upregulation of growth-restricting imprinted genes, including in the H19-Igf2
      locus, in long-term haematopoietic stem cells and their downregulation upon
      haematopoietic stem cell activation and proliferation. A differentially
      methylated region upstream of H19 (H19-DMR), serving as the imprinting control
      region, determines the reciprocal expression of H19 from the maternal allele and
      Igf2 from the paternal allele. In addition, H19 serves as a source of miR-675,
      which restricts Igf1r expression. We demonstrate that conditional deletion of the
      maternal but not the paternal H19-DMR reduces adult haematopoietic stem cell
      quiescence, a state required for long-term maintenance of haematopoietic stem
      cells, and compromises haematopoietic stem cell function. Maternal-specific H19
      DMR deletion results in activation of the Igf2-Igfr1 pathway, as shown by the
      translocation of phosphorylated FoxO3 (an inactive form) from nucleus to
      cytoplasm and the release of FoxO3-mediated cell cycle arrest, thus leading to
      increased activation, proliferation and eventual exhaustion of haematopoietic
      stem cells. Mechanistically, maternal-specific H19-DMR deletion leads to Igf2
      upregulation and increased translation of Igf1r, which is normally suppressed by
      H19-derived miR-675. Similarly, genetic inactivation of Igf1r partly rescues the
      H19-DMR deletion phenotype. Our work establishes a new role for this unique form
      of epigenetic control at the H19-Igf2 locus in maintaining adult stem cells. 

PMID- 23863939
TI  - Structure of class B GPCR corticotropin-releasing factor receptor 1.
AB  - Structural analysis of class B G-protein-coupled receptors (GPCRs), cell-surface
      proteins that respond to peptide hormones, has been restricted to the amino
      terminal extracellular domain, thus providing little understanding of the
      membrane-spanning signal transduction domain. The corticotropin-releasing factor
      receptor type 1 is a class B receptor which mediates the response to stress and
      has been considered a drug target for depression and anxiety. Here we report the
      crystal structure of the transmembrane domain of the human corticotropin
      releasing factor receptor type 1 in complex with the small-molecule antagonist CP
      376395. The structure provides detailed insight into the architecture of class B
      receptors. Atomic details of the interactions of the receptor with the non
      peptide ligand that binds deep within the receptor are described. This structure
      provides a model for all class B GPCRs and may aid in the design of new small
      molecule drugs for diseases of brain and metabolism. 

PMID- 23863940
TI  - Ptpn11 deletion in a novel progenitor causes metachondromatosis by inducing
      hedgehog signalling.
AB  - The tyrosine phosphatase SHP2, encoded by PTPN11, is required for the survival,
      proliferation and differentiation of various cell types. Germline activating
      mutations in PTPN11 cause Noonan syndrome, whereas somatic PTPN11 mutations cause
      childhood myeloproliferative disease and contribute to some solid tumours.
      Recently, heterozygous inactivating mutations in PTPN11 were found in
      metachondromatosis, a rare inherited disorder featuring multiple exostoses,
      enchondromas, joint destruction and bony deformities. The detailed pathogenesis
      of this disorder has remained unclear. Here we use a conditional knockout
      (floxed) Ptpn11 allele (Ptpn11(fl)) and Cre recombinase transgenic mice to delete
      Ptpn11 specifically in monocytes, macrophages and osteoclasts (lysozyme M-Cre;
      LysMCre) or in cathepsin K (Ctsk)-expressing cells, previously thought to be
      osteoclasts. LysMCre;Ptpn11(fl/fl) mice had mild osteopetrosis. Notably, however,
      CtskCre;Ptpn11(fl/fl) mice developed features very similar to metachondromatosis.
      Lineage tracing revealed a novel population of CtskCre-expressing cells in the
      perichondrial groove of Ranvier that display markers and functional properties
      consistent with mesenchymal progenitors. Chondroid neoplasms arise from these
      cells and show decreased extracellular signal-regulated kinase (ERK) pathway
      activation, increased Indian hedgehog (Ihh) and parathyroid hormone-related
      protein (Pthrp, also known as Pthlh) expression and excessive proliferation. Shp2
      deficient chondroprogenitors had decreased fibroblast growth factor-evoked ERK
      activation and enhanced Ihh and Pthrp expression, whereas fibroblast growth
      factor receptor (FGFR) or mitogen-activated protein kinase kinase (MEK) inhibitor
      treatment of chondroid cells increased Ihh and Pthrp expression. Importantly,
      smoothened inhibitor treatment ameliorated metachondromatosis features in
      CtskCre;Ptpn11(fl/fl) mice. Thus, in contrast to its pro-oncogenic role in
      haematopoietic and epithelial cells, Ptpn11 is a tumour suppressor in cartilage,
      acting through a FGFR/MEK/ERK-dependent pathway in a novel progenitor cell
      population to prevent excessive Ihh production. 

PMID- 23863941
TI  - Cell biology: tumour stem cells in bone.

PMID- 23863942
TI  - Translating dosage compensation to trisomy 21.
AB  - Down's syndrome is a common disorder with enormous medical and social costs,
      caused by trisomy for chromosome 21. We tested the concept that gene imbalance
      across an extra chromosome can be de facto corrected by manipulating a single
      gene, XIST (the X-inactivation gene). Using genome editing with zinc finger
      nucleases, we inserted a large, inducible XIST transgene into the DYRK1A locus on
      chromosome 21, in Down's syndrome pluripotent stem cells. The XIST non-coding RNA
      coats chromosome 21 and triggers stable heterochromatin modifications, chromosome
      wide transcriptional silencing and DNA methylation to form a 'chromosome 21 Barr
      body'. This provides a model to study human chromosome inactivation and creates a
      system to investigate genomic expression changes and cellular pathologies of
      trisomy 21, free from genetic and epigenetic noise. Notably, deficits in
      proliferation and neural rosette formation are rapidly reversed upon silencing
      one chromosome 21. Successful trisomy silencing in vitro also surmounts the major
      first step towards potential development of 'chromosome therapy'. 

PMID- 23863943
TI  - Potential use of synthetic alpha-galactosyl-containing glycotopes of the parasite
      Trypanosoma cruzi as diagnostic antigens for Chagas disease.
AB  - A synthetic glycoarray containing non-reducing alpha-galactopyranosyl moieties
      related to mucin O-glycans of the parasite Trypanosoma cruzi was evaluated by a
      chemiluminescent enzyme-linked immunosorbent assay with sera from patients with
      chronic Chagas disease. Our data revealed the disaccharide Galalpha(1,3)Galbeta
      as the immunodominant glycotope, which may eventually be employed as a diagnostic
      antigen for Chagas disease. 

PMID- 23863944
TI  - Synthesis of hierarchical three-dimensional copper oxide nanostructures through a
      biomineralization-inspired approach.
AB  - Three-dimensional (3D) copper oxide (CuO) nanostructures were synthesized in a
      regenerated Bombyx mori silk fibroin aqueous solution at room temperature. In the
      synthesis process, silk fibroin served as the template and helped to form the
      hierarchical CuO nanostructures by self-assembly. Cu(OH)2 nanowires were formed
      initially, and then they transformed into almond-like CuO nanostructures with
      branched edges and a compact middle. The size of the final CuO nanostructures can
      be tuned by varying the concentration of silk fibroin in the reaction system. A
      possible mechanism has been proposed based on various characterization
      techniques, such as scanning and transmission electron microscopy, X-ray
      diffraction, and thermogravimetric analysis. The synthesized CuO nanostructured
      material has been evaluated as an anode material for lithium ion batteries, and
      the result showed that they had a good electrochemical performance. The
      straightforward energy-saving method developed in this research may provide a
      useful preparation strategy for other functional inorganic materials through an
      environmentally friendly process. 

PMID- 23863945
TI  - Need for standardising adverse event reporting in testosterone trials.

PMID- 23863946
TI  - Psychotic symptoms and population risk for suicide attempt: a prospective cohort
      study.
AB  - IMPORTANCE: Up to 1 million persons die by suicide annually. However, a lack of
      risk markers makes suicide risk assessment one of the most difficult areas of
      clinical practice. OBJECTIVE: To assess psychotic symptoms (attenuated or frank)
      as a clinical marker of risk for suicide attempt. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective cohort study of 1112 school-based adolescents (aged 13
      16 years), assessed at baseline and at 3 and 12 months for self-reported
      psychopathology, psychotic symptoms, and suicide attempts. MAIN OUTCOMES AND
      MEASURES: Suicide attempts at the 3- and 12-month follow-up and acute suicide
      attempts (defined as those occurring in the 2 weeks before an assessment).
      RESULTS: Of the total sample, 7% reported psychotic symptoms at baseline. Of that
      subsample, 7% reported a suicide attempt by the 3-month follow-up compared with
      1% of the rest of the sample (odds ratio [OR], 10.01; 95% CI, 2.24-45.49), and
      20% reported a suicide attempt by the 12-month follow-up compared with 2.5% of
      the rest of the sample (OR, 11.27; 95% CI, 4.44-28.62). Among adolescents with
      baseline psychopathology who reported psychotic symptoms, 14% reported a suicide
      attempt by 3 months (OR, 17.91; 95% CI, 3.61-88.82) and 34% reported a suicide
      attempt by 12 months (OR, 32.67; 95% CI, 10.42-102.41). Adolescents with
      psychopathology who reported psychotic symptoms had a nearly 70-fold increased
      odds of acute suicide attempts (OR, 67.50; 95% CI, 11.41-399.21). Differences
      were not explained by nonpsychotic psychiatric symptom burden, multimorbidity, or
      substance use. In a causative model, the population-attributable fraction of
      suicide attempts would be 56% to 75% for psychotic symptoms. CONCLUSIONS AND
      RELEVANCE: Adolescents with psychopathology who report psychotic symptoms are at
      clinical high risk for suicide attempts. More careful clinical assessment of
      psychotic symptoms (attenuated or frank) in mental health services and better
      understanding of their pathological significance are urgently needed.

PMID- 23863947
TI  - High-Throughput Automated Phenotyping of Two Genetic Mouse Models of Huntington's
      Disease.
AB  - Phenotyping with traditional behavioral assays constitutes a major bottleneck in
      the primary screening, characterization, and validation of genetic mouse models
      of disease, leading to downstream delays in drug discovery efforts. We present a
      novel and comprehensive one-stop approach to phenotyping, the PhenoCubeTM. This
      system simultaneously captures the cognitive performance, motor activity, and
      circadian patterns of group-housed mice by use of home-cage operant conditioning
      modules (IntelliCage) and custom-built computer vision software. We evaluated two
      different mouse models of Huntington's Disease (HD), the R6/2 and the BACHD in
      the PhenoCubeTM system. Our results demonstrated that this system can efficiently
      capture and track alterations in both cognitive performance and locomotor
      activity patterns associated with these disease models. This work extends our
      prior demonstration that PhenoCubeTM can characterize circadian dysfunction in
      BACHD mice and shows that this system, with the experimental protocols used, is a
      sensitive and efficient tool for a first pass high-throughput screening of mouse
      disease models in general and mouse models of neurodegeneration in particular. 

PMID- 23863948
TI  - Synthesis, spectroscopic, electrochemical and computational studies of rhenium(I)
      dicarbonyl complexes based on meridionally-coordinated 2,2':6',2''-terpyridine.
AB  - A homologous series of meridionally-coordinated tridentate 2,2':6',2''
      terpyridine Re(I) dicarbonyl complexes have been prepared and investigated. The
      complexes mer,cis-[Re(tpy-kappa(3)N)(CO)2(L)](n) (L = Cl(-) (1), OSO2CF3(-) (2),
      NCCH3 (3), CN(-) (4), NC5H5 (5), PMe3 (6), PEt3 (7), PPh3 (8), P(OMe)3 (9) and
      P(OEt)3 (10); n = 0 or +1) have been synthesized and characterized by elemental
      analysis, (1)H NMR and infrared spectroscopy. The electrochemistry of these
      compounds has been studied and compared to that of other known rhenium compounds
      using an electrochemical parameterization model. Cyclic voltammetry measurements
      have shown that the first oxidation of the complexes varies systematically in
      potential as the ligand L is altered. Many of these one-electron oxidations occur
      at lower potentials compared to more familiar bidentate diimine Re(I) tricarbonyl
      complexes. A correlation exists between CO, a strong pi-acidic ligand, and
      deviations of the observed reduction potentials from the calculated values. Many
      of the complexes absorb light throughout a significant portion of the visible
      spectrum. Two of these complexes, mer,cis-Re(tpy-kappa(3)N)(CO)2Cl (1) and
      mer,cis-Re(tpy-kappa(3)N)(CO)2CN (4), absorb light throughout the entire visible
      spectrum. Low temperature emission spectra were obtained for the compounds
      mer,cis-Re(tpy-kappa(3)N)(CO)2Cl (1) and mer,cis-[Re(tpy
      kappa(3)N)(CO)2(P(OEt)3)](+) (10) at 77 K in a 4 : 1 methanol-ethanol glass
      matrix and give metal-to-ligand charge transfer ((3)MLCT) luminescence. Density
      functional theory (DFT) calculations of the electronic structure are in good
      agreement with the experimental data.

PMID- 23863949
TI  - Synthesis and decarboxylative Wittig reaction of difluoromethylene
      phosphobetaine.
AB  - A key intermediate, difluoromethylene phosphobetaine, in the Wittig reaction of
      ClCF2CO2Na-Ph3P with aldehydes was synthesized and characterized, which confirmed
      the reaction mechanism. The decarboxylation of this stable intermediate was a
      convenient approach for Wittig difluroolefination. Its reactivity could be
      adjusted by the modification of the substituent on the phosphorus. 

PMID- 23863952
TI  - Introduction: review series--Connected Health.

PMID- 23863950
TI  - Patients hospitalized with laboratory-confirmed influenza during the 2010-2011
      influenza season: exploring disease severity by virus type and subtype.
AB  - BACKGROUND:  The 2010-2011 influenza season was dominated by influenza A(H3N2)
      virus, but influenza A(H1N1) pdm09 (pH1N1) and B viruses cocirculated. This
      provided an opportunity to explore within-season predictors of severity among
      hospitalized patients, avoiding biases associated with season-to-season
      differences in strain virulence, population immunity, and healthcare seeking.
      METHODS:  Population-based, laboratory-confirmed influenza hospitalization
      surveillance data were used to examine the association between virus type/subtype
      and outcomes in children and adults. Multivariable analysis explored virus
      type/subtype, prompt antiviral treatment, medical conditions, and age as
      predictors for severity (intensive care unit admission or death). RESULTS:  In
      children, pH1N1 (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI],
      1.11-4.3), chronic metabolic disease (aOR, 5.23; 95% CI, 1.74-15.69), and
      neuromuscular disorder (aOR, 4.84; 95% CI, 2.02-11.58) were independently
      associated with severity. In adults, independent predictors were pH1N1 (aOR,
      2.21; 95% CI, 1.66-2.94), chronic lung disease (aOR, 1.46, 95% CI, 1.12-1.89),
      and neuromuscular disorder (aOR, 1.68; 95% CI, 1.11-2.52).Antiviral treatment
      reduced the odds of severity among adults (aOR, 0.47; 95% CI, .33-.68).
      CONCLUSIONS:  During the 2010-2011 season, pH1N1 caused more severe disease than
      H3N2 or B in hospitalized patients. Underlying medical conditions increased
      severity despite virus strain. Antiviral treatment reduced severity among adults.
      Our findings underscore the importance of influenza prevention.

PMID- 23863953
TI  - Weighted gene coexpression network analysis of human left atrial tissue
      identifies gene modules associated with atrial fibrillation.
AB  - BACKGROUND: Genetic mechanisms of atrial fibrillation (AF) remain incompletely
      understood. Previous differential expression studies in AF were limited by small
      sample size and provided limited understanding of global gene networks, prompting
      the need for larger-scale, network-based analyses. METHODS AND RESULTS: Left
      atrial tissues from Cleveland Clinic patients who underwent cardiac surgery were
      assayed using Illumina Human HT-12 mRNA microarrays. The data set included 3
      groups based on cardiovascular comorbidities: mitral valve (MV) disease without
      coronary artery disease (n=64), coronary artery disease without MV disease
      (n=57), and lone AF (n=35). Weighted gene coexpression network analysis was
      performed in the MV group to detect modules of correlated genes. Module
      preservation was assessed in the other 2 groups. Module eigengenes were regressed
      on AF severity or atrial rhythm at surgery. Modules whose eigengenes correlated
      with either AF phenotype were analyzed for gene content. A total of 14 modules
      were detected in the MV group; all were preserved in the other 2 groups. One
      module (124 genes) was associated with AF severity and atrial rhythm across all
      groups. Its top hub gene, RCAN1, is implicated in calcineurin-dependent signaling
      and cardiac hypertrophy. Another module (679 genes) was associated with atrial
      rhythm in the MV and coronary artery disease groups. It was enriched with cell
      signaling genes and contained cardiovascular developmental genes including TBX5.
      CONCLUSIONS: Our network-based approach found 2 modules strongly associated with
      AF. Further analysis of these modules may yield insight into AF pathogenesis by
      providing novel targets for functional studies.

PMID- 23863954
TI  - Homozygous founder mutation in desmocollin-2 (DSC2) causes arrhythmogenic
      cardiomyopathy in the Hutterite population.
AB  - BACKGROUND: Dominant mutations in cellular junction proteins are the major cause
      of arrhythmogenic cardiomyopathy, whereas recessive mutations in those proteins
      cause cardiocutaneous syndromes such as Naxos and Carvajal syndrome. The
      Hutterites are distinct genetic isolates who settled in North America in 1874.
      Descended from <100 founders, they trace their origins to 16th-century Europe.
      METHODS AND RESULTS: We clinically and genetically evaluated 2 large families of
      the Alberta Hutterite population with a history of sudden death and found several
      individuals with severe forms of biventricular cardiomyopathy characterized by
      mainly left-sided localized aneurysms, regions of wall thinning with segmental
      akinesis, in addition to typical electric and histological features known for
      arrhythmogenic right ventricular cardiomyopathy. We identified a homozygous
      truncation mutation, c.1660C>T (p.Q554X) in desmocollin-2 (DSC2), in affected
      individuals and determined a carrier frequency of this mutation of 9.4% (1 in
      10.6) among 1535 Schmiedeleut Hutterites, suggesting a common founder in that
      subgroup. Immunohistochemistry of endomyocardial biopsy samples revealed altered
      expression of the truncated DSC2 protein at the intercalated discs but only minor
      changes in immunoreactivity of other desmosomal proteins. Recombinant expressed
      mutant DSC2 protein in cells confirmed a stable, partially processed truncated
      protein with cytoplasmic and membrane localization. CONCLUSIONS: A homozygous
      truncation mutation in DSC2 leads to a cardiac-restricted phenotype of an early
      onset biventricular arrhythmogenic cardiomyopathy. The truncated protein remains
      partially stable and localized at the intercalated discs. These data suggest that
      the processed DSC2 protein plays a role in maintaining desmosome integrity and
      function.

PMID- 23863955
TI  - Memory suppression trades prolonged fear and sleep-dependent fear plasticity for
      the avoidance of current fear.
AB  - Sleep deprivation immediately following an aversive event reduces fear by
      preventing memory consolidation during homeostatic sleep. This suggests that
      acute insomnia might act prophylactically against the development of
      posttraumatic stress disorder (PTSD) even though it is also a possible risk
      factor for PTSD. We examined total sleep deprivation and memory suppression to
      evaluate the effects of these interventions on subsequent aversive memory
      formation and fear conditioning. Active suppression of aversive memory impaired
      retention of event memory. However, although the remembered fear was more reduced
      in sleep-deprived than sleep-control subjects, suppressed fear increased, and
      seemed to abandon the sleep-dependent plasticity of fear. Active memory
      suppression, which provides a psychological model for Freud's ego defense
      mechanism, enhances fear and casts doubt on the potential of acute insomnia as a
      prophylactic measure against PTSD. Our findings bring into question the role of
      sleep in aversive-memory consolidation in clinical PTSD pathophysiology. 

PMID- 23863956
TI  - Ascorbic acid inhibits ferric nitrilotriacetate induction of ornithine
      decarboxylase, DNA synthesis, oxidative stress, and hepatotoxicity in rats.
AB  - Ascorbic acid (AA) is a naturally occurring phenolic compound with antioxidant
      properties used in food, cosmetics, and pharmaceutical products. In this study,
      the effect of AA on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in
      rats has been examined. Fe-NTA alone enhances ornithine decarboxylase activity to
      4.5-fold and tritiated thymidine incorporation in DNA to 3.6-fold in livers
      compared with the corresponding saline-treated controls. The enhanced ornithine
      decarboxylase activity and DNA synthesis showed a reduction to 3.02- and 1.88
      fold, respectively, at a higher dose of 2 mg AA per day per animal, compared with
      the Fe-NTA-treated groups. Fe-NTA treatment also enhanced the hepatic microsomal
      lipid peroxidation to 1.7-fold compared to saline-treated controls. These changes
      were reversed significantly in animals receiving pretreatment of AA. The present
      data shows that AA can reciprocate the toxic effects of Fe-NTA and can serve as a
      potent chemopreventive agent to suppress oxidant-induced tissue injury and
      hepatotoxicity in rats.

PMID- 23863957
TI  - Biological studies on the effect of estrogen on experimentally induced asthma in
      mice.
AB  - This study evaluates the influence of estrogen hormone on the experimentally
      induced asthma in male mice. The animals were divided into four groups, with 20
      mice in each group; group I (control mice) included mice that received no
      treatment, group II included mice that received intraperitoneal estrogen
      injection (0.25 mg/kg body weight (bw), twice on day 28 of the experiment), group
      III (asthmatic mice) included asthmatic mice that received intraperitoneal
      injection of two doses of ovalbumin (OVA; 2 ug of OVA mixed with 100 ug of
      aluminum potassium sulfate) on days 1 and 14 of the experiment and then
      challenged intranasally with a single dose of OVA (50 ug dissolved in 0.05 ml
      phosphate-buffered saline; PBS) on day 28 of the experiment, and group IV
      (asthmatic mice treated with estrogen) included asthma model male mice that
      received the estrogen (0.5 mg/kg bw in 40 ml PBS, twice on the day 28 of the
      experiment). The immunohistochemical studies observed a marked intensity of CD15
      immunoreactivity in the lung tissues of asthma model mice. Physiological results
      recorded that the total and differential count of leukocytes in bronchoalveolar
      lavage fluid (BALF) of asthma model mice recorded a significant increase in the
      number of leukocytes especially in the number of eosinophil cells. The BALF of
      asthma model mice showed high levels of interleukins 4 and 5 (IL-4 and IL-5), and
      there was a significant decrease in both the levels of IL-4 and IL-5 in BALF of
      asthma model mice treated with estrogen. In conclusion, the obtained results
      indicated that the asthma is responsible for certain immunohistochemical and
      physiological alterations induced in lung tissues of mice. The administration of
      estrogen to asthmatic male mice could improve these changes. For this reason, the
      present findings support the possible role of estrogen in modulating the
      inflammatory effects caused by asthma in male mice and may be helpful to cure
      many asthmatic progressions. 

PMID- 23863958
TI  - First total synthesis of (+)-apotrisporin E and (+)-apotrientriols A-B: a
      cyclization approach to apocarotenoids.
AB  - The first total synthesis of the natural apocarotenoids (+)-apotrisporin E (1)
      and (+)-apotrientriols A and B (2-3) has been accomplished. The structure,
      relative stereochemistry and the assignation of the absolute configuration have
      been confirmed. This is a fast and easy access to this family of natural products
      whose key steps are a diastereoselective cyclization and a HWE olefination to
      attach the dienic side chain. This work also opens the door to the synthesis of
      other apocarotenoids such as trisporols and trisporic acids.

PMID- 23863959
TI  - One-pot synthesis of monodispersed silica nanoparticles for diarylethene-based
      reversible fluorescence photoswitching in living cells.
AB  - A small 29 nm monodispersed silica nanoparticle 1a was synthesized as a
      diarylethene-based reversible fluorescence photoswitch by copolymerizing silane
      precursors in one-pot including 3a and 4. Reversible photoswitching of
      nanoparticle 1a was successfully achieved in living cells to show its potential
      as a highly distinguishable and safe fluorescence probe for cell tracking.

PMID- 23863960
TI  - Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized,
      single-masked, placebo-controlled study.
AB  - IMPORTANCE: Sarcoidosis is a chronic granulomatous disease for which there are
      limited therapeutic options. This is the first randomized, placebo-controlled
      study to demonstrate that antimycobacterial therapy reduces lesion diameter and
      disease severity among patients with chronic cutaneous sarcoidosis. OBJECTIVE: To
      evaluate the safety and efficacy of once-daily antimycobacterial therapy on the
      resolution of chronic cutaneous sarcoidosis lesions. DESIGN AND PARTICIPANTS: A
      randomized, placebo-controlled, single-masked trial on 30 patients with
      symptomatic chronic cutaneous sarcoidosis lesions deemed to require therapeutic
      intervention. SETTING: A tertiary referral dermatology center in Nashville,
      Tennessee. INTERVENTIONS: Participants were randomized to receive either the oral
      concomitant levofloxacin, ethambutol, azithromycin, and rifampin (CLEAR) regimen
      or a comparative placebo regimen for 8 weeks with a 180-day follow-up. MAIN
      OUTCOMES AND MEASURES: Participants were monitored for absolute change in lesion
      diameter and decrease in granuloma burden, if present, on completion of therapy.
      OBSERVATIONS: In the intention-to-treat analysis, the CLEAR-treated group had a
      mean (SD) decrease in lesion diameter of -8.4 (14.0) mm compared with an increase
      of 0.07 (3.2) mm in the placebo-treated group (P = .05). The CLEAR group had a
      significant reduction in granuloma burden and experienced a mean (SD) decline of 
      2.9 (2.5) mm in lesion severity compared with a decline of -0.6 (2.1) mm in the
      placebo group (P = .02). CONCLUSIONS AND RELEVANCE: Antimycobacterial therapy may
      result in significant reductions in chronic cutaneous sarcoidosis lesion diameter
      compared with placebo. These observed reductions, associated with a clinically
      significant improvement in symptoms, were present at the 180-day follow-up
      period. Transcriptome analysis of sarcoidosis CD4+ T cells revealed reversal of
      pathways associated with disease severity and enhanced T-cell function following
      T-cell receptor stimulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01074554.

PMID- 23863961
TI  - The toxicity of selected trace metals to Lecane inermis rotifers isolated from
      activated sludge.
AB  - The aim of the study was to assess the toxicity of a range of trace metals to the
      rotifer Lecane inermis, a species tested as a potential biological tool to
      control activated sludge bulking caused by overgrowth of filamentous bacteria in
      wastewater treatment plants. LC50 values (concentration lethal to 50 % of
      individuals, mg dm(-3)) were ranked in the following order: Cu < Al < Fe < Zn <
      Sn < Mn. L. inermis apparently is more sensitive to metals than other aquatic
      species widely used as model organisms in ecotoxicological testing, making it
      potentially useful for quick ecotoxicological tests.

PMID- 23863962
TI  - Chief resident operative experience: a moving target.

PMID- 23863963
TI  - Poor people view hospitals as providing better access, care, and social support.

PMID- 23863964
TI  - Non-adherence to medication increases stroke risk in patients with high blood
      pressure.

PMID- 23863965
TI  - Health secretary puts 11 hospital trusts in England into special measures.

PMID- 23863966
TI  - Potential antitumor agent from the endophytic fungus Pestalotiopsis photiniae
      induces apoptosis via the mitochondrial pathway in HeLa cells.
AB  - 4-(3',3'-Dimethylallyloxy)-5-methyl-6-methoxy-phthalide (DMMP) has previously
      been isolated from the endophytic fungus Pestalotiopsis photiniae. Although the
      cytotoxic activities of DMMP have been reported, little is known concerning the
      molecular mechanism of its cytotoxic effect. In the present study, we
      investigated the effect of DMMP on the growth of several types of cancer cell
      lines and investigated the mechanism of its antiproliferative effect. DMMP caused
      the growth inhibition of human cancer lines HeLa, MCF7 and MDA-MB-231, but had
      little antiproliferative effect on MRC5 normal lung cells. DMMP also
      significantly caused cell cycle arrest in the G1 phase and upregulated the cyclin
      dependent kinase inhibitor p27KIPI protein in the HeLa cells. Moreover DMMP was
      able to induce marked nuclear apoptotic morphology in HeLa cells. DMMP induced
      apoptosis and loss of mitochondrial membrane potential (DeltaPsim) in the HeLa
      cells. Although the activated forms of caspase-9 and -3 in HeLa cells were
      detected, pretreatment with caspase inhibitors (Ac-DEVD-CHO and Z-VAD-FMK) failed
      to attenuate DMMP-induced cell death. In addition, protein levels of the p53
      family members, p53 and p73, were upregulated, and DMMP significantly increased
      the mRNA expression of pro-apoptotic Bcl-2 family genes (PUMA, NOXA, Bax, Bad and
      Bim). HPV E6-E7 mRNA levels were reduced. In conclusion, DMMP demonstrates
      potential for use in the treatment of cervical cancer.

PMID- 23863967
TI  - Designing tensile ductility in metallic glasses.
AB  - Effectiveness of a second phase in metallic glass heterostructures to improve
      mechanical properties varies widely. Unfortunately, methods to fabricate such
      heterostructures like foams and composites do not allow controlled variation of
      structural features. Here we report a novel strategy, which allows us to vary
      heterostructural features independently, thereby enabling a systematic and
      quantitative study. Our approach reveals the optimal microstructural architecture
      for metallic glass heterostructures to achieve tensile ductility. Critical design
      aspect is a soft second phase, which is most effective when spacing between the
      second phase assumes the critical crack length of the metallic glass. This
      spacing should coincide with the second phase's size, and beyond, the specific
      second phase morphology of the heterostructure is crucial. These toughening
      strategies are only effective in samples that are large compared with the spacing
      of the second phase. The identified design aspects provide guidance in designing
      tensile ductility into metallic glasses. 

PMID- 23863968
TI  - Pirt functions as an endogenous regulator of TRPM8.
AB  - Pirt is a membrane protein that is specifically expressed in the peripheral
      nervous system, where it has been shown to increase the sensitivity of the
      transient receptor potential vanilloid 1 channel and modulate its role in heat
      pain. The broad expression of Pirt among dorsal root ganglion neurons suggests it
      may modulate other transient receptor potentials, such as the menthol and cooling
      sensor TRPM8. The discrepancies in the channel properties of TRPM8 in native
      neurons versus heterologous cells indicate the existence of endogenous modulators
      of the channel. Here we show that Pirt regulates the function of TRPM8 and its
      role in detecting cold. Pirt(-/-) mice exhibit decreased behavioural responses to
      cold and cool temperatures, and Pirt increases the sensitivity of TRPM8 to
      menthol and cool temperature. Our data suggest Pirt is an endogenous regulator of
      TRPM8. 

PMID- 23863969
TI  - Bis(tetrabenzotriazaporphyrinato) and
      (tetrabenzotriazaporphyrinato)(phthalocyaninato) lutetium(III) complexes--novel
      sandwich-type tetrapyrrolic ligand based NIR absorbing electrochromes.
AB  - The first sandwich-type complexes have been prepared for
      tetrabenzotriazaporphyrin ligands. The compounds reveal intrinsic UV-Vis/NIR
      absorption as well as peculiar electrochromic behavior. The heteroleptic
      (tetrabenzotriazaporphyrinato)(phthalocyaninato) lutetium derivative shows
      intermediate spectral and electrochemical properties with respect to homoleptic
      relatives.

PMID- 23863970
TI  - Personality-targeted interventions delivered by teachers may be effective at
      reducing alcohol use.

PMID- 23863971
TI  - Gender differences in reasons to quit smoking among adolescents.
AB  - It is well established that many adolescents who smoke want to quit, but little
      is known about why adolescents want to quit and if reasons to quit differ across
      gender. The objective of this study was to determine if reasons to quit smoking
      differ in boys and girls. Data on the Adolescent Reasons for Quitting (ARFQ)
      scale were collected in mailed self-report questionnaires in 2010-2011 from 113
      female and 83 male smokers aged 14-19 years participating in AdoQuest, a
      longitudinal cohort study of the natural course of the co-occurrence of health
      compromising behaviors in children. Overall, the findings indicate that reasons
      to quit in boys and girls appear to be generally similar, although this finding
      may relate to a lack of gender-oriented items in the ARFQ scale. There is a need
      for continued research to develop and test reasons to quit scales for adolescents
      that include gender-oriented items. 

PMID- 23863972
TI  - Nesprin-1 plays an important role in the proliferation and apoptosis of
      mesenchymal stem cells.
AB  - The aim of this study was to investigate the expression of nesprin-1 protein and
      its effects on rat bone marrow mesenchymal stem cells (MSCs). MSCs were cultured
      in DMEM and surface-associated antigens of MSCs were detected by flow cytometry.
      The protein expression of nesprin-1 was detected by immunofluorescence and
      western blot analysis. A lentiviral vector expressing small interfering RNA
      (siRNA) targeting nesprin-1 was constructed (LV-siNesprin-1) and the MSCs were
      subsequently transfected with this vector. Another group of MSCs was transfected
      with the LV-GFP vector and another group of untransfected cells was used as the
      controls (normal group). The protein expression level of nesprin-1 in the 3
      groups of MSCs (LV-siNesprin-1, LV-GFP and normal group) was measured by western
      blot analysis. Cell proliferation was assessed by MTT assay, and the cell cycle
      and apoptosis were detected by flow cytometry. DAPI was used to stain the nucleus
      of the MSCs. The MSCs appeared spindle-shaped with irregular processes and were
      positive for CD90, CD29 and negative for CD45. Nesprin-1 protein was found in the
      nuclear membrane. The protein expression of nesprin-1 in the LV-siNesprin-1 group
      was lower than that in the LV-GFP (P=0.03) and normal group (P=0.028); this
      difference was significant (P<0.05). The cell proliferation of the MSCs
      transfected with LV-siNesprin-1 was reduced; the apoptotic rate was higher in the
      LV-siNesprin-1 group compared with the other 2 groups (LV-GFP and normal group)
      (P=0.032, P=0.025, respectively; P<0.05). The changes in the morphology of the
      nucleus in the LV-siNesprin-1 group included fusion and fragmentation. In
      conclusion, the data presented in this study indicate that nesprin-1 regulates
      the proliferation and apoptosis of MSCs; our results are consistent with those
      from previous studies. Thus, nesprin-1 protein plays an important role in the
      proliferation and apoptosis of MSCs.

PMID- 23863973
TI  - Synthesis of Pt-Ni/graphene via in situ reduction and its enhanced catalyst
      activity for methanol oxidation.
AB  - A simple in situ reduction approach was used to obtain Pt3Ni/reduced graphene
      oxide (rGO) with dominant {111} facets. The catalytic activity of Pt-Ni/rGO
      toward methanol electro-oxidation was studied by performing cyclic voltammetry.
      The Pt3Ni/rGO nanocatalysts exhibited improved catalytic activity and durability.

PMID- 23863974
TI  - Managing the apparent and hidden difficulties of weaning from mechanical
      ventilation.
AB  - BACKGROUND: In anaesthetized patients scheduled for surgery, tracheal intubation
      is performed with the expectation of subsequent smooth extubation. In critically
      ill patients, separation from the ventilator is often gradual and the time chosen
      for extubation may be either delayed or premature. Thus, weaning is challenging,
      represents a large part of the ventilation period and concerns all mechanically
      ventilated patients surviving their stay. DEFINITIONS AND MANAGEMENT: Weaning may
      be stratified in three groups according to its difficulty and duration. In simple
      weaning the main issue is to detect the soonest time to start separation from the
      ventilator; this is frequently impeded by poor sedation management and excessive
      ventilator assistance. A two-step diagnostic approach is the most efficacious:
      screening for ascertained readiness to wean is confirmed by a diagnostic test
      simulating the post-extubation period, best performed by unassisted breathing (no
      PEEP). In case of test failure (difficult weaning), a structured and thorough
      diagnostic work-up regarding potentially reversible pathologies is required with
      a focus on cardiovascular dysfunction or fluid overload at the time of separation
      from the ventilator, respiratory or global muscle weakness and underlying
      infection. Prolonged weaning is exceptionally time- and resource-consuming, needs
      to properly appraise psychological problems, sleep and nutrition, and is probably
      best performed in specialized units. CONCLUSIONS: Adequately managing simple and
      difficult weaning requires one to think about ICU policies in terms of sedation,
      fluid balance and having a systematic screening strategy; it also needs an
      individualized approach to understand and treat the failing patients. Prolonged
      weaning requires a holistic approach.

PMID- 23863976
TI  - Necochea, my personal Ithaca.

PMID- 23863975
TI  - Increased perioperative mortality following aprotinin withdrawal: a real-world
      analysis of blood management strategies in adult cardiac surgery.
AB  - PURPOSE: To evaluate the effect of aprotinin withdrawal in 2008 on patient
      outcomes, to assess the likely risks and benefits of its re-introduction, and to
      consider the relevance of existing evidence from clinical trials to 'real-world'
      practice. METHODS: We performed a nested case-control study of two cohorts
      undergoing adult cardiac surgery in a single tertiary centre. The first group
      underwent surgery between 1 January 2005 and 30 July 2007 (n = 3,578), prior to
      aprotinin withdrawal; the second group underwent surgery between 1 January 2009
      and 31 December 2010 (n = 3,030), after aprotinin withdrawal. Propensity matching
      was used to select patients matched for 24 covariates in both groups (n = 3,508).
      We also estimated the effect of aprotinin withdrawal on a subgroup of high-risk
      patients (n = 1,002). Results were expressed as adjusted odds ratios (OR) and 95%
      confidence intervals (CI) for categorical data and hazard ratios (HR) for time-to
      event data. RESULTS: In propensity-matched cohorts, the withdrawal of aprotinin
      from clinical use was associated with more bleeding, higher rates of emergency re
      sternotomy, OR 2.10 (1.04-4.25), and acute kidney injury (AKI), OR 1.86 (1.53
      2.25). In high-risk patients, the increases in bleeding and AKI following
      aprotinin withdrawal were of a greater magnitude. Aprotinin withdrawal was also
      associated with a significant increase in 30-day mortality, HR 2.51 (1.00-6.29),
      in the high-risk group. The results were not altered by sensitivity analyses that
      adjusted for potential selection bias, time series bias and unmeasured
      confounders. CONCLUSIONS: Aprotinin withdrawal was associated with increased
      complication rates and patient deaths following cardiac surgery. These real-world
      findings are at odds with those of randomised trials and cohort studies that have
      considered the clinical role of aprotinin.

PMID- 23863977
TI  - Cortical stimulation consolidates and reactivates visual experience: neural
      plasticity from magnetic entrainment of visual activity.
AB  - Delivering transcranial magnetic stimulation (TMS) shortly after the end of a
      visual stimulus can cause a TMS-induced 'replay' or 'visual echo' of the visual
      percept. In the current study, we find an entrainment effect that after repeated
      elicitations of TMS-induced replay with the same visual stimulus, the replay can
      be induced by TMS alone, without the need for the physical visual stimulus. In
      Experiment 1, we used a subjective rating task to examine the phenomenal aspects
      of TMS-entrained replays. In Experiment 2, we used an objective masking paradigm
      to quantitatively validate the phenomenon and to examine the involvement of low
      level mechanisms. Results showed that the TMS-entrained replay was not only
      phenomenally experienced (Exp.1), but also able to hamper letter identification
      (Exp.2). The findings have implications in several directions: (1) the visual
      cortical representation and iconic memory, (2) experience-based plasticity in the
      visual cortex, and (3) their relationship to visual awareness. 

PMID- 23863978
TI  - A comprehensive study of the crystallization mechanism involved in the nonaqueous
      formation of tungstite.
AB  - We present a detailed study on the nonaqueous synthesis of tungstite
      nanostructures with the focus on crystallization processes and the evolution of
      particle morphology. Time-dependent transmission electron microscopy (TEM)
      revealed a complex, particle-based crystallization mechanism involving first the
      formation of spherical and single-crystalline primary particles of 2-8 nm, which
      are cross-linked to large and unordered agglomerates, followed by their
      organization into rod-like structures of 40 * 200-400 nm. These rods undergo an
      internal ordering process, during which crystallographically oriented stacks of
      platelets develop. In situ small angle X-ray scattering (SAXS) experiments
      confirm this pathway of particle formation. The scattering intensity is dominated
      by the fast formation of rod-like particles, which cause an inter-platelet peak
      in the SAXS pattern with ongoing internal ordering. With continuous reaction
      time, the platelet stacks start to fall apart forming shorter assemblies of just
      a few platelets or even single platelets. 

PMID- 23863979
TI  - One-pot synthesis of S-alkyl dithiocarbamates via the reaction of N
      tosylhydrazones, carbon disulfide and amines.
AB  - A new, convenient and efficient transition metal-free synthesis of S-alkyl
      dithiocarbamates through one-pot reaction of N-tosylhydrazones, carbon disulfide
      and amines is reported. Tosylhydrazones derived from various aromatic and
      aliphatic ketones or aldehydes were tested and gave dithiocarbamates in good to
      excellent yields. The tosylhydrazones can be generated in situ without isolation,
      which provides a simpler one-pot method to synthesize dithiocarbamates via the
      reaction of carbonyl compounds, carbon disulfide and amines in the presence of 4
      methylbenzenesulfonohydrazide. 

PMID- 23863980
TI  - Noninvasive assessment of pulmonary hemodynamics in patients with chronic
      thromboembolic pulmonary hypertension by high temporal resolution phase-contrast
      MRI: correlation with simultaneous invasive pressure recordings.
AB  - BACKGROUND: Right heart catheterization is the gold standard for assessment of
      pulmonary hemodynamics in patients with chronic thromboembolic pulmonary
      hypertension. To date, MRI has not been able to produce precise measurements of
      mean pulmonary arterial pressure (mPAP). The purpose of the study was to create a
      model for estimating mPAP and pulmonary vascular resistance in patients with
      chronic thromboembolic pulmonary hypertension by high temporal resolution phase
      contrast MRI (PC-MRI) and to correlate the results with simultaneously acquired,
      invasive catheter-based measurements (simultaneously measured mPAP) and with
      right heart catheterization measurements. METHODS AND RESULTS: A total of 19
      patients with chronic thromboembolic pulmonary hypertension underwent right heart
      catheterization and-after digital subtraction angiography of the pulmonary
      arteries-subsequent PC-MRI at 1.5 T with simultaneous recording of mPAP. Velocity
      and flow-time curves of PC-MRI were used to calculate absolute acceleration time
      (Ata), maximum of mean velocities (MV), volume of acceleration (AV), and maximum
      flow acceleration (dQ/dt). On the basis of these parameters, multiple linear
      regression analysis revealed maximum achievable model fit (B=0.902) for the
      following linear combination equation to calculate mPAP (mPAP_cal):
      mPAP_cal=69.446-(0.521 * Ata)-(0.570 * MV)+(1.507 * AV)+(0.002 * dQ/dt). There
      was a statistically significant equivalence of mPAP_cal and simultaneously
      measured mPAP with a goodness of fit of 0.892. Pulmonary vascular resistance was
      overestimated by calculated pulmonary vascular resistance on the basis of PC-MRI
      in comparison with right heart catheterization-based measurements by a median of 
      112 dyn.s.cm(-5), the pairwise regression formula revealed a goodness of fit of
      0.792. CONCLUSIONS: PC-MRI-derived parameters enable noninvasive assessment of
      pulmonary hemodynamics in patients with chronic thromboembolic pulmonary
      hypertension.

PMID- 23863982
TI  - Efficient oxygen evolution reaction catalyzed by low-density Ni-doped Co3O4
      nanomaterials derived from metal-embedded graphitic C3N4.
AB  - A synthetic route to low-density porous Ni-doped Co3O4 nanomaterials that show
      stable and superior electrocatalytic activity for O2 evolution reaction is
      reported. The materials are prepared via thermal treatment of "pre-synthesized"
      metal ions-embedded graphitic C3N4-based polymers. 

PMID- 23863983
TI  - Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and
      cardiometabolic risk in young adults.
AB  - Studies in mature adults suggest that the plasma concentration ratio of
      triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify
      apparently healthy individuals who are insulin resistant (IR) and at increased
      cardiometabolic risk. This study extends these observations by examining the
      clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244
      healthy college students (17-24 years old) of Mexican Mestizo ancestry. The
      TG/HDL-C ratio separating the 25% with the highest value was used to identify IR
      and increased cardiometabolic risk. Cardiometabolic risk factors were more
      adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5,
      respectively, and approximately one third were identified as being IR. The MetS
      identified fewer individuals as being IR, but their risk profile was accentuated.
      In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify
      young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C
      ratio identified a somewhat greater number of "high risk" subjects, whereas the
      MetS found a group whose risk profile was somewhat magnified. These findings
      suggest that the TG/HDL-C ratio may serve as a simple and clinically useful
      approach to identify apparently healthy, young individuals who are IR and at
      increased cardiometabolic risk. 

PMID- 23863984
TI  - Anti-metastatic and differential effects on protein expression of
      epigallocatechin-3-gallate in HCCLM6 hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the
      third highest cause of cancer-related mortality in humans. Epigallocatechin-3
      gallate (EGCG) has been shown to inhibit the metastatic activity of certain
      cancer cells. The aim of this study was to determine the effects and molecular
      mechanism(s) of action of EGCG in human HCC cells. A migration and invasion assay
      for the metastatic behavior of HCCLM6 cells was performed. The anti-metastatic
      effects of EGCG were investigated by RT-PCR and gelatin zymography. A total
      cellular protein profile was obtained using 2-dimensional gel electrophoresis (2
      DE), followed by matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-TOF-MS) analyses of proteins with significant differences in
      expression following treatment with EGCG. The results revealed that EGCG induced
      apoptosis and inhibited the metastasis of HCCLM6 cells. The anti-metastatic
      effects of EGCG were associated with the inhibition of matrix metalloproteinase
      (MMP)-2 and MMP-9 activity. The expression levels of far upstream element (FUSE)
      binding protein 1 (FUBP1), heat shock protein beta 1 (HSPB1), heat shock 60 kDa
      protein 1 (chaperonin) (CH60) and nucleophosmin (NPM) proteins, which are
      associated with metastasis, were significantly altered in the EGCG-treated HCCLM6
      cells. The data from the present study suggest that EGCG has potential as a
      therapeutic agent for the treatment of HCC.

PMID- 23863986
TI  - We should harness the power of our colleagues' fresh ideas.

PMID- 23863985
TI  - Noninvasive fractal biomarker of clock neurotransmitter disturbance in humans
      with dementia.
AB  - Human motor activity has a robust, intrinsic fractal structure with similar
      patterns from minutes to hours. The fractal activity patterns appear to be
      physiologically important because the patterns persist under different
      environmental conditions but are significantly altered/reduced with aging and
      Alzheimer's disease (AD). Here, we report that dementia patients, known to have
      disrupted circadian rhythmicity, also have disrupted fractal activity patterns
      and that the disruption is more pronounced in patients with more amyloid plaques
      (a marker of AD severity). Moreover, the degree of fractal activity disruption is
      strongly associated with vasopressinergic and neurotensinergic neurons (two major
      circadian neurotransmitters) in postmortem suprachiasmatic nucleus (SCN), and can
      better predict changes of the two neurotransmitters than traditional circadian
      measures. These findings suggest that the SCN impacts human activity regulation
      at multiple time scales and that disrupted fractal activity may serve as a non
      invasive biomarker of SCN neurodegeneration in dementia. 

PMID- 23863987
TI  - Identification of a KIR antisense lncRNA expressed by progenitor cells.
AB  - Human NK cells express cell surface class I MHC receptors (killer cell
      immunoglobulin-like receptor, KIR) in a probabilistic manner. Previous studies
      have shown that a distal promoter acts in conjunction with a proximal
      bidirectional promoter to control the selective activation of KIR genes. We
      report here the presence of an intron 2 promoter in several KIR genes that
      produce a spliced antisense transcript. This long noncoding RNA (lncRNA)
      transcript contains antisense sequence complementary to KIR-coding exons 1 and 2
      as well as the proximal promoter region of the KIR genes. The antisense promoter
      contains myeloid zinc finger 1 (MZF-1)-binding sites, a transcription factor
      found in hematopoietic progenitors and myeloid precursors. The KIR antisense
      lncRNA was detected only in progenitor cells or pluripotent cell lines,
      suggesting a function that is specific for stem cells. Overexpression of MZF-1 in
      developing NK cells led to decreased KIR expression, consistent with a role for
      the KIR antisense lncRNA in silencing KIR gene expression early in development. 

PMID- 23863988
TI  - Ex vivo dermoscopy for biobank-oriented sampling of melanoma.
AB  - IMPORTANCE: In the era of targeted therapy for cancer, translational research
      identifying molecular targets in melanoma offers novel opportunities for
      potential new treatments. OBJECTIVES: To describe a method for sampling fresh
      tissue from primary melanoma and to test whether the area of maximal thickness
      can be identified with dermoscopy to ensure it remains available for routine
      histopathological diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Tumors clinically
      suspicious for melanoma with diameter exceeding 5 mm were included. Dermoscopy
      guided sampling was performed using a 2-mm to 3-mm punch through not the thickest
      part of the tumor. In vivo and ex vivo dermoscopic images obtained were available
      to the diagnosing pathologist. Melanoma samples were obtained in a referral
      melanoma unit. MAIN OUTCOMES AND MEASURES: In study 1, Breslow thickness in 10
      melanomas was compared between sampled tissue and the remaining specimen to
      confirm that the area of maximal thickness remained available for the
      histopathological diagnosis. In study 2, forty-three additional melanomas were
      sampled for biobanking prospectively. Agreement between 2 independent observers
      on dermoscopic identification of the thickest part of the melanoma was studied.
      RESULTS: In study 1, the area of maximal Breslow thickness in all 10 melanomas
      was not sampled and remained in the main specimen. In study 2, sampling was
      performed by one of the investigators. Concordance was 93% between 2 independent
      observers for the dermoscopic selection of the thickest portion of the melanoma.
      Pathologists asserted that the sampling procedure did not compromise their
      ability to evaluate melanoma specimens. A limitation is that this is a single
      center study. Each case required joint evaluation by expert dermoscopists and
      dermatopathologists. CONCLUSIONS AND RELEVANCE: In applying the dermoscopy-guided
      sampling protocol, we make the following 5 recommendations: Samples should only
      be obtained from areas that will not interfere with the pathologist's diagnosis
      and prognostic information. Sampling should not be obtained from tumors for which
      one suspects that the histopathological evaluation may prove difficult. Sampling
      should not be performed on small melanomas; we recommend a minimum diameter of 10
      mm. All the dermoscopy-guided sampling should be documented with images,
      available to pathologists and clinicians, and reflected in the pathology report.
      Finally, the frozen biobank samples should be made available for routine
      hematoxylin-eosin histopathological evaluation until the final pathology report
      is produced. Ex vivo dermoscopy may serve to guide the procurement of small
      samples from primary melanoma for fresh tissue biobanking without compromising
      the histopathological evaluation.

PMID- 23863989
TI  - Near-infrared pigments based on ion-pair charge transfer salts of dicationic and
      dianionic metal-dithiolene [M(II) = Pd, Pt] complexes.
AB  - Mixing [M(Et2dazdt)2](BF4)2 [M = Ni(II), Pd(II), Pt(II); Et2dazdt = N,N'-diethyl
      perhydrodiazepine-2,3-dithione] with (Bu4N)2[M(mnt)2] (mnt = maleonitrile-2,3
      dithiolate) in CH3CN produces the known mixed ligand dithiolene complex
      [Ni(Et2dazdt)(mnt)] in the nickel case and ion-pair salts [M(Et2dazdt)2][M(mnt)2]
      in the palladium (1) and platinum (2) cases. Structural characterization of 2
      shows that the anionic (donor) and cationic (acceptor) complexes form an
      irregular stack that lies in the bc crystallographic plane. The shortest contacts
      exchanged by the anion and cation molecules within each stack are those occurring
      through the hydrogen atoms of the CH2 groups of Et2dazdt and the Pt(2)-S(22)
      segment (d(H(81a)-S(22) = 2.981(3) A) and the nitrogen atom of the cyano group of
      mnt and the carbon atom of one of the thione moieties (d(N(12)-C(11) = 3.179(3)
      A). The Pt atom of [Pt(mnt)2](2-) is surrounded by two hydrogen atoms of the
      Et2dazdt ligand, whereas the Pt atom of [Pt(Et2dazdt)2](2+) is surrounded by two
      carbon atoms of the dithiolate moiety of mnt. Intramolecular interactions are due
      to contacts exchanged mainly through H-atoms, which are suitable to mediate
      charge-transfer (CT) interactions. In fact, these salts are characterized by a
      long wavelength CT peak [lambdamax = 905 nm (1), 937 nm (2)], which makes them
      candidates as near-infrared pigments, whose properties are tunable with the redox
      features of the components, the energy of the NIR absorption being relatable to
      the driving force of electron transfer from the donor (dianion) to the acceptor
      (dication). A thorough description of interactions occurring between the complex
      anions and complex cations has been achieved by investigating the Hirshfeld
      surface (HS) properties. Computational methods are in agreement with experimental
      findings and allow us to highlight the electronic features of the components of
      these CT salts, providing a structure-property relationship, useful in designing
      new candidates to optimize the desired properties.

PMID- 23863992
TI  - Interactions of newly designed dicationic carbazole derivatives with double
      stranded DNA: syntheses, binding studies and AFM imaging.
AB  - The design of small molecular ligands able to bind with DNA is pivotal for the
      development of diagnostic agents and therapeutic drugs targeting DNA. Carbazole
      derivatives are potential agents against tumors and opportunistic infections of
      AIDS. Here, two carbazole-derived dicationic compounds, DPDI and DPPDI, were
      designed, synthesized and characterized using NMR, IR and MS. The DNA binding
      properties of DPDI and DPPDI were sensitive to ionic strength. At low ionic
      strength, planar and aromatic DPDI had a strongly intercalative interaction with
      DNA, which was confirmed by circular dichroism (CD) and gel electrophoresis. In
      DPPDI, a phenyl group substituting H atom at the -NH group of DPDI destroyed
      molecular planarity, which resulted in no intercalative interactions between
      DPPDI and DNA, proved by CD. The positive enhancement of CD at 260-270 nm and
      Hoechst 33258 competitive binding tests indicated the strong groove interactions
      of both DPPDI and DPDI to DNA. The similarity and difference in the structures
      between DPDI and DPPDI explained different interaction preferences with DNA. In
      groove interactions, dications of pyridinium on either DPDI or DPPDI could
      interact with DNA base pairs, and -NH on DPDI or -N-Ph on DPPDI pointed out of
      the groove, as the classical model of DNA groove binding agents. Furthermore, AFM
      imaging revealed that both carbazole-derivatives drove the DNA conformation more
      compact. All the experimental data proved that the two dicationic carbazole
      derivatives interacted with DNA strongly and might act as a novel type of DNA
      binding candidate.

PMID- 23863990
TI  - The intravertebral distribution of bone density: correspondence to intervertebral
      disc health and implications for vertebral strength.
AB  - This study's goal was to determine associations among the intravertebral
      heterogeneity in bone density, bone strength, and intervertebral disc (IVD)
      health. Results indicated that predictions of vertebral strength can benefit from
      considering the magnitude of the density heterogeneity and the congruence between
      the spatial distribution of density and IVD health. INTRODUCTION: This study aims
      to determine associations among the intravertebral heterogeneity in bone density,
      bone strength, and IVD health METHODS: Regional measurements of bone density were
      performed throughout 30 L1 vertebral bodies using micro-computed tomography
      (MUCT) and quantitative computed tomography (QCT). The magnitude of the
      intravertebral heterogeneity in density was defined as the interquartile range
      and quartile coefficient of variation in regional densities. The spatial
      distribution of density was quantified using ratios of regional densities
      representing different anatomical zones (e.g., anterior to posterior regional
      densities). Cluster analysis was used to identify groups of vertebrae with
      similar spatial distributions of density. Vertebral strength was measured in
      compression. IVD health was assessed using two scoring systems. RESULTS: QCT- and
      MUCT-based measures of the magnitude of the intravertebral heterogeneity in
      density were strongly correlated with each other (p < 0.005). Accounting for the
      interquartile range in regional densities improved predictions of vertebral
      strength as compared to predictions based only on mean density (R (2) = 0.59 vs.
      0.43; F-test p-value = 0.018). Specifically, after adjustment for mean density,
      vertebral bodies with greater heterogeneity in density exhibited higher strength.
      No single spatial distribution of density was associated with high vertebral
      strength. Analyses of IVD scores suggested that the health of the adjacent IVDs
      may modulate the effect of a particular spatial distribution of density on
      vertebral strength. CONCLUSIONS: Noninvasive measurements of the intravertebral
      distribution of bone density, in conjunction with assessments of IVD health, can
      aid in predictions of bone strength and in elucidating biomechanical mechanisms
      of vertebral fracture.

PMID- 23863993
TI  - Surgical site infection: is it time to change our expectations?

PMID- 23863994
TI  - Reply to the 'Comment on "The structure and formation of hydrogen-bonded
      molecular networks on Au(111) surfaces revealed by scanning tunnelling and
      torsional-tapping atomic force microscopy"' by I. Cebula, M. T. Raisanen, R.
      Madueno, B. Karamzadeh and M. Buck, Phys. Chem. Chem. Phys., 2013, 15, DOI:
      10.1039/c3cp50754h.

PMID- 23863995
TI  - Short, terminally modified 2'-OMe RNAs as inhibitors of microRNA.
AB  - We applied 14-mer 2'-OMe RNAs as inhibitors of selected micro RNAs. To improve
      their properties, we introduced a trimethoxystilbene residue at the 5'-terminus
      and three 2'-fluoro-2'-deoxynucleotides at the 3'-terminus to obtain potent
      inhibitors, whose mismatch discrimination is substantially better than that of
      typically applied >18-mers.

PMID- 23863996
TI  - The Weil osteotomy for correction of the severe rheumatoid forefoot.
AB  - PURPOSE: In rheumatoid arthritis the metatarsophalangeal (MTP) joints are
      predominantly affected with resultant metatarsalgia and dislocation. Therapy
      options include many different surgical procedures with results that are not
      always satisfying. We present the oblique Weil metatarsal osteotomy as a
      treatment option for the rheumatic forefoot. METHODS: A total of 216 osteotomies
      in 63 consecutive patients (72 feet) with a mean age at the time of surgery of
      59.3 years and long-standing rheumatoid arthritis were observed prospectively for
      an average of 57.4 months (minimum 36 months). All patients received a Weil
      osteotomy of the lesser metatarsals with at least one additional procedure of the
      forefoot. Patients were evaluated prospectively for clinical outcome by the
      American Orthopaedic Foot and Ankle Society (AOFAS) lesser MTP-interphalangeal
      scale and subjective satisfaction. In the radiological evaluation weight-bearing
      X-rays were analysed for alignment, shortening and union. RESULTS: American
      Orthopaedic Foot and Ankle Society score increased significantly from 21.9 +/-
      6.7 to 63.3 +/- 9.8 (p < 0.05). The increase was significant for all subgroups
      regarding pain, function and alignment. All joints were dorsally dislocated
      preoperatively; a subluxation was present in 13.6 % at follow-up. There was a
      significant decrease of callositas in 82 %, a decrease in need for orthopaedic
      shoes in 61 %, a decrease of MTP joint stiffness in 96 % and a relief of severe
      pain in 97 % of all patients. No metatarsal head dislocation or necrosis,
      pseudoarthrosis or screw perforation was observed. Of 63 patients, 55 (88 %)
      subjectively reported excellent or good results. CONCLUSIONS: We conclude that
      the Weil procedure for lesser metatarsals is a satisfactory method for correcting
      the rheumatic forefoot and can be recommended as an approach for the future.

PMID- 23863997
TI  - Efficient p-type dye-sensitized solar cells based on disulfide/thiolate
      electrolytes.
AB  - Herein, an organic redox couple 1-methy-1H-tetrazole-5-thiolate (T(-)) and its
      disulfide dimer (T2) redox shuttle, as an electrolyte, is introduced in a p-type
      dye-sensitized solar cell (DSC) on the basis of an organic dye (P1) sensitizer
      and nanocrystal CuCrO2 electrode. Using this iodide-free transparent redox
      electrolyte in conjunction with the sensitized heterojunction, we achieve a high
      open-circuit voltage of over 300 mV. An optimal efficiency of 0.23% is obtained
      using a CoS counter electrode and an optimized electrolyte composition under AM
      1.5 G 100 mW cm(-2) light illumination which, to the best of our knowledge,
      represents the highest efficiency that has so far been reported for p-type DSCs
      using organic redox couples. 

PMID- 23863998
TI  - Femtolitre chemistry assisted by microfluidic pen lithography.
AB  - Chemical reactions at ultrasmall volumes are becoming increasingly necessary to
      study biological processes, to synthesize homogenous nanostructures and to
      perform high-throughput assays and combinatorial screening. Here we show that a
      femtolitre reaction can be realized on a surface by handling and mixing
      femtolitre volumes of reagents using a microfluidic stylus. This method, named
      microfluidic pen lithography, allows mixing reagents in isolated femtolitre
      droplets that can be used as reactors to conduct independent reactions and
      crystallization processes. This strategy overcomes the high-throughput
      limitations of vesicles and micelles and obviates the usually costly step of
      fabricating microdevices and wells. We anticipate that this process enables
      performing distinct reactions (acid-base, enzymatic recognition and metal-organic
      framework synthesis), creating multiplexed nanoscale metal-organic framework
      arrays, and screening combinatorial reactions to evaluate the crystallization of
      novel peptide-based materials. 

PMID- 23863999
TI  - CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by
      mesenchymal stem cells through VEGF.
AB  - Chemokines and chemokine receptor 4 (CXCR4) play an important role in metastasis.
      CXCR4 is also expressed in the human osteosarcoma cell line 9607-F5M2 (F5M2),
      which has a high tumorigenic ability and potential for spontaneous pulmonary
      metastasis. Mesenchymal stem cells (MSCs) contribute to the formation of the
      tumor stroma and promote metastasis. However, mechanisms underlying the promotion
      of osteosarcoma growth and pulmonary metastasis by MSCs are still elusive. Our
      study co-injected the human MSCs and F5M2 cells into the caudal vein of nude
      mice. The total number of tumor nodules per lung was significantly increased in
      the F5M2+MSC group compared to the other groups (control, F5M2 cells alone and
      MSCs alone) at week six. Moreover, a high number of Dil-labeled MSCs was present
      also at the osteosarcoma metastasis sites in the lung. Using Transwell assays, we
      found that F5M2 cells migrate towards MSCs, while the CXCR4 inhibitor AMD3100
      decreased the migration potential of F5M2 cells towards MSCs. Furthermore, upon
      treatment with F5M2-conditioned medium, MSCs expressed and secreted higher levels
      of VEGF as determined by immunohistochemistry, western blotting and ELISA,
      respectively. Importantly, co-cultured with F5M2 cells, MSCs expressed and
      secreted higher VEGF levels, while AMD3100 dramatically decreased the VEGF
      secretion by MSCs. However, CXCR4 expression on F5M2 cells was not significantly
      increased in the co-culture system. Additionally, VEGF increased the
      proliferation of both MSCs and F5M2 cells. These findings suggest that CXCR4
      mediated osteosarcoma growth and pulmonary metastasis are promoted by MSCs
      through VEGF. 

PMID- 23864000
TI  - Interfacial liquid-state surface-enhanced Raman spectroscopy.
AB  - Oriented assemblies of functional nanoparticles, with the aid of external
      physical and chemical driving forces, have been prepared on two-dimensional solid
      substrates. It is challengeable, however, to achieve three-dimensional assembly
      directly in solution, owing to thermal fluctuations and free diffusion. Here we
      describe the self-orientation of gold nanorods at an immiscible liquid interface
      (that is, oleic acid-water) and exploit this novel phenomenon to create a
      substrate-free interfacial liquid-state surface-enhanced Raman spectroscopy. Dark
      field imaging and Raman scattering results reveal that gold nanorods
      spontaneously adopt a vertical orientation at an oleic acid-water interface in a
      stable trapping mode, which is in good agreement with simulation results. The
      spontaneous vertical alignment of gold nanorods at the interface allows one to
      accomplish significant additional amplification of the Raman signal, which is up
      to three to four orders of magnitude higher than that from a solution of randomly
      oriented gold nanorods. 

PMID- 23864001
TI  - A local dormancy cline is related to the seed maturation environment, population
      genetic composition and climate.
AB  - BACKGROUND AND AIMS: Seed dormancy varies within species in response to climate,
      both in the long term (through ecotypes or clines) and in the short term (through
      the influence of the seed maturation environment). Disentangling both processes
      is crucial to understand plant adaptation to environmental changes. In this
      study, the local patterns of seed dormancy were investigated in a narrow endemic
      species, Centaurium somedanum, in order to determine the influence of the seed
      maturation environment, population genetic composition and climate. METHODS:
      Laboratory germination experiments were performed to measure dormancy in (1)
      seeds collected from different wild populations along a local altitudinal
      gradient and (2) seeds of a subsequent generation produced in a common garden.
      The genetic composition of the original populations was characterized using
      intersimple sequence repeat (ISSR) PCR and principal co-ordinate analysis (PCoA),
      and its correlation with the dormancy patterns of both generations was analysed.
      The effect of the local climate on dormancy was also modelled. KEY RESULTS: An
      altitudinal dormancy cline was found in the wild populations, which was
      maintained by the plants grown in the common garden. However, seeds from the
      common garden responded better to stratification, and their release from dormancy
      was more intense. The patterns of dormancy variation were correlated with genetic
      composition, whereas lower temperature and summer precipitation at the population
      sites predicted higher dormancy in the seeds of both generations. CONCLUSIONS:
      The dormancy cline in C. somedanum is related to a local climatic gradient and
      also corresponds to genetic differentiation among populations. This cline is
      further affected by the weather conditions during seed maturation, which
      influence the receptiveness to dormancy-breaking factors. These results show that
      dormancy is influenced by both long-and short-term climatic variation. Such
      processes at such a reduced spatial scale highlight the potential of plants to
      adapt to fast environmental changes.

PMID- 23864002
TI  - Mutualistic ants contribute to tank-bromeliad nutrition.
AB  - BACKGROUND AND AIMS: Epiphytism imposes physiological constraints resulting from
      the lack of access to the nutrient sources available to ground-rooted plants. A
      conspicuous adaptation in response to that lack is the phytotelm (plant-held
      waters) of tank-bromeliad species that are often nutrient-rich. Associations with
      terrestrial invertebrates also result in higher plant nutrient acquisition.
      Assuming that tank-bromeliads rely on reservoir-assisted nutrition, it was
      hypothesized that the dual association with mutualistic ants and the phytotelm
      food web provides greater nutritional benefits to the plant compared with those
      bromeliads involved in only one of these two associations. METHODS: Quantitative
      (water volume, amount of fine particulate organic matter, predator/prey ratio,
      algal density) and qualitative variables (ant-association and photosynthetic
      pathways) were compared for eight tank- and one tankless-bromeliad morphospecies
      from French Guiana. An analysis was also made of which of these variables affect
      nitrogen acquisition (leaf N and delta(15)N). KEY RESULTS: All variables were
      significantly different between tank-bromeliad species. Leaf N concentrations and
      leaf delta(15)N were both positively correlated with the presence of mutualistic
      ants. The amount of fine particulate organic matter and predator/prey ratio had a
      positive and negative effect on leaf delta(15)N, respectively. Water volume was
      positively correlated with leaf N concentration whereas algal density was
      negatively correlated. Finally, the photosynthetic pathway (C3 vs. CAM) was
      positively correlated with leaf N concentration with a slightly higher N
      concentration for C3-Tillandsioideae compared with CAM-Bromelioideae.
      CONCLUSIONS: The study suggests that some of the differences in N nutrition
      between bromeliad species can be explained by the presence of mutualistic ants.
      From a nutritional standpoint, it is more advantageous for a bromeliad to use
      myrmecotrophy via its roots than to use carnivory via its tank. The results
      highlight a gap in our knowledge of the reciprocal interactions between
      bromeliads and the various trophic levels (from bacteria to large metazoan
      predators) that intervene in reservoir-assisted nutrition.

PMID- 23864003
TI  - Soybean leaf hydraulic conductance does not acclimate to growth at elevated [CO2]
      or temperature in growth chambers or in the field.
AB  - BACKGROUND AND AIMS: Leaf hydraulic properties are strongly linked with
      transpiration and photosynthesis in many species. However, it is not known if gas
      exchange and hydraulics will have co-ordinated responses to climate change. The
      objective of this study was to investigate the responses of leaf hydraulic
      conductance (Kleaf) in Glycine max (soybean) to growth at elevated [CO2] and
      increased temperature compared with the responses of leaf gas exchange and leaf
      water status. METHODS: Two controlled-environment growth chamber experiments were
      conducted with soybean to measure Kleaf, stomatal conductance (gs) and
      photosynthesis (A) during growth at elevated [CO2] and temperature relative to
      ambient levels. These results were validated with field experiments on soybean
      grown under free-air elevated [CO2] (FACE) and canopy warming. KEY RESULTS: In
      chamber studies, Kleaf did not acclimate to growth at elevated [CO2], even though
      stomatal conductance decreased and photosynthesis increased. Growth at elevated
      temperature also did not affect Kleaf, although gs and A showed significant but
      inconsistent decreases. The lack of response of Kleaf to growth at increased
      [CO2] and temperature in chamber-grown plants was confirmed with field-grown
      soybean at a FACE facility. CONCLUSIONS: Leaf hydraulic and leaf gas exchange
      responses to these two climate change factors were not strongly linked in
      soybean, although gs responded to [CO2] and increased temperature as previously
      reported. This differential behaviour could lead to an imbalance between
      hydraulic supply and transpiration demand under extreme environmental conditions
      likely to become more common as global climate continues to change.

PMID- 23864005
TI  - Fifteen-minute consultation: A structured approach to the management of
      hypermobility in a child.
AB  - OBJECTIVE: To present a structured approach for an outpatient consultation of a
      child with hypermobility. METHOD: Review of the literature and a description of
      the approach commonly adopted in a paediatric out-patient setting. CONCLUSIONS: A
      focused history and examination is the key to reaching an appropriate
      differential diagnosis and planning management for children with hypermobility.
      CASE: A 10-year-old child is referred to your general paediatric clinic with
      frequent 'cracking and clicking' of her joints and a history of intermittent
      aches and pains over the last 6 months.

PMID- 23864004
TI  - Harnessing apomictic reproduction in grasses: what we have learned from Paspalum.
AB  - BACKGROUND: Apomixis is an alternative route of plant reproduction that produces
      individuals genetically identical to the mother plant through seeds. Apomixis is
      desirable in agriculture, because it guarantees the perpetuation of superior
      genotypes (i.e. heterotic hybrid seeds) by self-seeding without loss of hybrid
      vigour. The Paspalum genus, an archetypal model system for mining apomixis
      gene(s), is composed of about 370 species that have extremely diverse
      reproductive systems, including self-incompatibility, self-fertility, full sexual
      reproduction, and facultative or obligate apomixis. Barriers to interspecific
      hybridization are relaxed in this genus, allowing the production of new hybrids
      from many different parental combinations. Paspalum is also tolerant to various
      parental genome contributions to the endosperm, allowing analyses of how sexually
      reproducing crop species might escape from dosage effects in the endosperm.
      SCOPE: In this article, the available literature characterizing apomixis in
      Paspalum spp. and its use in breeding is critically reviewed. In particular, a
      comparison is made across species of the structure and function of the genomic
      region controlling apomixis in order to identify a common core region shared by
      all apomictic Paspalum species and where apomixis genes are likely to be
      localized. Candidate genes are discussed, either as possible genetic determinants
      (including homologs to signal transduction and RNA methylation genes) or as
      downstream factors (such as cell-to-cell signalling and auxin response genes)
      depending, respectively, on their co-segregation with apomixis or less.
      Strategies to validate the role of candidate genes in apomictic process are also
      discussed, with special emphasis on plant transformation in natural apomictic
      species.

PMID- 23864006
TI  - Intervention for recoarctation in the single ventricle reconstruction trial:
      incidence, risk, and outcomes.
AB  - BACKGROUND: Recoarctation after the Norwood procedure increases risk for
      mortality. The Single Ventricle Reconstruction (SVR) trial randomized subjects
      with a single right ventricle undergoing a Norwood procedure to a modified
      Blalock-Taussig shunt or a right ventricle-pulmonary artery shunt. We sought to
      determine the incidence of recoarctation, risk factors, and outcomes in the SVR
      trial. METHODS AND RESULTS: Recoarctation was defined by intervention, either
      catheter based or surgical. Univariate analysis and multivariable Cox
      proportional hazard models were performed with adjustment for center. Of the 549
      SVR subjects, 97 (18%) underwent 131 interventions (92 balloon aortoplasty, 39
      surgical) for recoarctation at a median age of 4.9 months (range, 1.1-10.5
      months). Intervention typically occurred at pre-stage II catheterization (n=71,
      54%) or at stage II surgery (n=38, 29%). In multivariable analysis, recoarctation
      was associated with the shunt type in place at the end of the Norwood procedure
      (hazard ratio, 2.0 for right ventricle-pulmonary artery shunt versus modified
      Blalock-Taussig shunt; P=0.02), and Norwood discharge peak echo-Doppler arch
      gradient (hazard ratio, 1.07 per 1 mm Hg; P<0.01). Subjects with recoarctation
      demonstrated comorbidities at pre-stage II evaluation, including higher pulmonary
      arterial pressures (15.4+/-3.0 versus 14.5+/-3.5 mm Hg; P=0.05), higher pulmonary
      vascular resistance (2.6+/-1.6 versus 2.0+/-1.0 Wood units.m(2); P=0.04), and
      increased echocardiographic volumes (end-diastolic volume, 126+/-39 versus 112+/
      33 mL/BSA(1.3), where BSA is body surface area; P=0.02). There was no difference
      in 12-month postrandomization transplantation-free survival between those with
      and without recoarctation (P=0.14). CONCLUSIONS: Recoarctation is common after
      Norwood and contributes to pre-stage II comorbidities. Although with intervention
      there is no associated increase in 1-year transplantation/mortality, further
      evaluation is warranted to evaluate the effects of associated morbidities.

PMID- 23864007
TI  - Anesthetic regimen for cardiac function evaluation by echocardiography in mice:
      comparison between ketamine, etomidate and isoflurane versus conscious state.
AB  - Mice with genetic alterations are used in heart research for the extrapolation of
      human diseases. Echocardiography is an essential tool for evaluating cardiac and
      hemodynamic functions in small animals. The purpose of this study was to compare
      the effect of different anesthetic regimens and the conscious state on the
      evaluation of cardiac function by echocardiography. Mice were examined in the
      conscious state after three days of training, and then for a 7 min period after a
      single intraperitoneal injection of ketamine at 100 mg/kg, etomidate at 10, 20 or
      30 mg/kg, or after inhalation of isoflurane at 1.5% with or without a short
      period of induction with isoflurane 3%. Intra- and inter-observer variabilities
      were assessed. The operator's comfort was also assessed. Heart rate, left
      ventricular end diastolic diameter, fraction shortening and cardiac output were
      measured using echocardiography. Ketamine at 5 and 7 min after induction and
      isoflurane at 3, 5 and 7 min after induction provided good anesthetic conditions
      and a quick awakening time, and did not influence cardiac performance, whereas
      the conscious state was associated with a non-physiological sympathetic
      activation and other anesthetic drugs induced a significant decrease in heart
      rate. Etomidate 10 mg/kg and 20 mg/kg were not enough to provide adequate
      anesthesia. Etomidate 30 mg/kg induced a good anesthetic condition but influenced
      cardiac performance and had a long awakening time. Our results indicate that
      ketamine and isoflurane with a short induction period are better anesthetic drugs
      than isoflurane without induction or etomidate for evaluating cardiac function in
      healthy mice.

PMID- 23864008
TI  - Efficient microwave-assisted synthetic protocols and in silico behaviour
      prediction of per-substituted beta-cyclodextrins.
AB  - Selective per-substituted cyclodextrin design enables the carrier's
      physicochemical and binding properties to be tailored and can even modify some
      biological native structure effects. We herein report a number of highly
      efficient microwave-assisted synthetic protocols for the preparation of several
      amino, ureido and thioureido per-substituted beta-cyclodextrin derivatives. A
      rapid parallel synthetic approach has given a set of 14 different CD derivatives.
      Our strategy is supported by computational analyses which were used to estimate
      the physicochemical behaviour of per-substituted derivatives and to tailor
      suitable substituents. 

PMID- 23864009
TI  - Two FLX family members are non-redundantly required to establish the
      vernalization requirement in Arabidopsis.
AB  - Studies of natural genetic variation for the vernalization requirement in
      Arabidopsis have revealed two genes, FRIGIDA and FLOWERING LOCUS C (FLC), that
      are determinants of the vernalization-requiring, winter-annual habit. In this
      study, we show that FLOWERING LOCUS C EXPRESSOR-LIKE 4 (FLL4) is essential for
      upregulation of FLC in winter-annual Arabidopsis accessions and establishment of
      a vernalization requirement. FLL4 is part of the FLOWERING LOCUS C EXPRESSOR gene
      family and both are non-redundantly involved in flowering time control. Epistasis
      analysis among FRIGIDA, FLL4, FLOWERING LOCUS C EXPRESSOR and autonomous-pathway
      genes reveals that FRIGIDA fve exhibits an extreme delay of flowering compared
      with fri fve, but mutants in other autonomous-pathway genes do not, indicating
      that FVE acts most antagonistically to FRIGIDA. FLL4 may represent a new member
      of a FRI-containing complex that activates FLC. 

PMID- 23864010
TI  - Differential effects of an exotic plant virus on its two closely related vectors.
AB  - Concurrent spread of Tomato yellow leaf curl virus (TYLCV) with invasion of
      Bemisia tabaci Q rather than B in China suggests a more mutualistic relationship
      between TYLCV and Q than B. To assess this hypothesis, we quantified the impacts
      of TYLCV on the performance and competitiveness of B and Q in the laboratory. The
      results showed that relative to their non-infected counterparts feeding on cotton
      (a non-host for TYLCV), infected B exhibited significant reductions in life
      history traits, whereas infected Q only showed marginal reductions. While Q
      performed better on TYLCV-infected tomato plants than on uninfected ones, the
      reverse was observed in B. Q displacement by B took one more generation on TYLCV
      infected tomato plants than on healthy ones. These results demonstrate that TYLCV
      was indirectly mutualistic to Q but directly and indirectly parasitic to B. 

PMID- 23864011
TI  - Experimental design and instability analysis of coaxial electrospray process for
      microencapsulation of drugs and imaging agents.
AB  - Recent developments in multimodal imaging and image-guided therapy requires
      multilayered microparticles that encapsulate several imaging and therapeutic
      agents in the same carrier. However, commonly used microencapsulation processes
      have multiple limitations such as low encapsulation efficiency and loss of
      bioactivity for the encapsulated biological cargos. To overcome these
      limitations, we have carried out both experimental and theoretical studies on
      coaxial electrospray of multilayered microparticles. On the experimental side, an
      improved coaxial electrospray setup has been developed. A customized coaxial
      needle assembly combined with two ring electrodes has been used to enhance the
      stability of the cone and widen the process parameter range of the stable cone
      jet mode. With this assembly, we have obtained poly(lactide-co-glycolide)
      microparticles with fine morphology and uniform size distribution. On the
      theoretical side, an instability analysis of the coaxial electrified jet has been
      performed based on the experimental parameters. The effects of process parameters
      on the formation of different unstable modes have been studied. The reported
      experimental and theoretical research represents a significant step toward
      quantitative control and optimization of the coaxial electrospray process for
      microencapsulation of multiple drugs and imaging agents in multimodal imaging and
      image-guided therapy.

PMID- 23864012
TI  - Modeling the shape of cylindrically focused transducers in three-dimensional
      optoacoustic tomography.
AB  - Cross sectional tomographic systems based on cylindrically focused transducers
      are widely used in optoacoustic (photoacoustic) imaging due to important
      advantages they provide such as high-cross sectional resolution, real-time
      imaging capacity, and high-throughput performance. Tomographic images in such
      systems are commonly obtained by means of two-dimensional (2-D) reconstruction
      procedures assuming point-like detectors, and volumetric (whole-body) imaging is
      performed by superimposing the cross sectional images for different positions
      along the scanning direction. Such reconstruction strategy generally leads to in
      plane and out-of-plane artifacts as well as significant quantification errors.
      Herein, we introduce two equivalent full three-dimensional (3-D) models capable
      of accounting for the shape of cylindrically focused transducers. The performance
      of these models in 3-D reconstructions considering several scanning positions is
      analyzed in this work. Improvements of the results rendered with the introduced
      reconstruction procedure as compared with the 2-D-based approach are described
      and discussed for simulations and experiments with phantoms and biological
      tissues.

PMID- 23864013
TI  - Optimization of confocal scanning laser ophthalmoscope design.
AB  - Confocal scanning laser ophthalmoscopy (cSLO) enables high-resolution and high
      contrast imaging of the retina by employing spatial filtering for scattered light
      rejection. However, to obtain optimized image quality, one must design the cSLO
      around scanner technology limitations and minimize the effects of ocular
      aberrations and imaging artifacts. We describe a cSLO design methodology
      resulting in a simple, relatively inexpensive, and compact lens-based cSLO design
      optimized to balance resolution and throughput for a 20-deg field of view (FOV)
      with minimal imaging artifacts. We tested the imaging capabilities of our cSLO
      design with an experimental setup from which we obtained fast and high signal-to
      noise ratio (SNR) retinal images. At lower FOVs, we were able to visualize
      parafoveal cone photoreceptors and nerve fiber bundles even without the use of
      adaptive optics. Through an experiment comparing our optimized cSLO design to a
      commercial cSLO system, we show that our design demonstrates a significant
      improvement in both image quality and resolution.

PMID- 23864014
TI  - Use of Split Bregman denoising for iterative reconstruction in fluorescence
      diffuse optical tomography.
AB  - Fluorescence diffuse optical tomography (fDOT) is a noninvasive imaging technique
      that makes it possible to quantify the spatial distribution of fluorescent
      tracers in small animals. fDOT image reconstruction is commonly performed by
      means of iterative methods such as the algebraic reconstruction technique (ART).
      The useful results yielded by more advanced l1-regularized techniques for signal
      recovery and image reconstruction, together with the recent publication of Split
      Bregman (SB) procedure, led us to propose a new approach to the fDOT inverse
      problem, namely, ART-SB. This method alternates a cost-efficient reconstruction
      step (ART iteration) with a denoising filtering step based on minimization of
      total variation of the image using the SB method, which can be solved efficiently
      and quickly. We applied this method to simulated and experimental fDOT data and
      found that ART-SB provides substantial benefits over conventional ART.

PMID- 23864015
TI  - Photometric stereo endoscopy.
AB  - While color video endoscopy has enabled wide-field examination of the
      gastrointestinal tract, it often misses or incorrectly classifies lesions. Many
      of these missed lesions exhibit characteristic three-dimensional surface
      topographies. An endoscopic system that adds topographical measurements to
      conventional color imagery could therefore increase lesion detection and improve
      classification accuracy. We introduce photometric stereo endoscopy (PSE), a
      technique which allows high spatial frequency components of surface topography to
      be acquired simultaneously with conventional two-dimensional color imagery. We
      implement this technique in an endoscopic form factor and demonstrate that it can
      acquire the topography of small features with complex geometries and
      heterogeneous optical properties. PSE imaging of ex vivo human gastrointestinal
      tissue shows that surface topography measurements enable differentiation of
      abnormal shapes from surrounding normal tissue. Together, these results confirm
      that the topographical measurements can be obtained with relatively simple
      hardware in an endoscopic form factor, and suggest the potential of PSE to
      improve lesion detection and classification in gastrointestinal imaging.

PMID- 23864016
TI  - Optical detection of gold nanoparticles in a prostate-shaped porcine phantom.
AB  - Gold nanoparticles can be used as molecular contrast agents binding specifically
      to cancer sites and thus delineating tumor regions. Imaging gold nanoparticles
      deeply embedded in tissues with optical techniques possesses significant
      challenges due to multiple scattering of optical photons that blur the obtained
      images. Both diagnostic and therapeutic applications can benefit from a minimally
      invasive technique that can identify, localize, and quantify the payloads of gold
      nanoparticles deeply embedded in biological tissues. An optical radiance
      technique is applied to map localized inclusions of gold nanorods in 650- to 900
      nm spectral range in a porcine phantom that mimics prostate geometry. Optical
      radiance defines a variation in the angular density of photons impinging on a
      selected point in the tissue from various directions. The inclusions are formed
      by immersing a capillary filled with gold nanorods in the phantom at increasing
      distances from the detecting fiber. The technique allows the isolation of the
      spectroscopic signatures of the inclusions from the background and identification
      of inclusion locations in the angular domain. Detection of ~4*1010 gold
      nanoparticles or 0.04  mg Au/mL (detector-inclusion separation 10 mm, source
      detector separation 15 mm) in the porcine tissue is demonstrated. The encouraging
      results indicate a promising potential of radiance spectroscopy in early prostate
      cancer diagnostics with gold nanoparticles.

PMID- 23864017
TI  - Two-photon excited quantum dots as energy donors for photosensitizer chlorin e6.
AB  - The excitation-related problems in photodynamic therapy of cancer might be solved
      by combining two-photon (TP) irradiation and quantum dots (QDs) as effective
      energy donors for conventional photosensitizers (PS). Here, it is demonstrated
      for the first time that QD-chlorin e6 (Ce6) complex formed due to the hydrophobic
      interaction between Ce6 molecules and lipid coating of QDs can be effectively
      excited via TP irradiation at 1030 nm, which spectrally coincides with the
      biological tissue optical window. TP absorption cross-section for free QDs and
      Ce6 at 1030 nm was 3325 and 13 Goeppert-Mayer, respectively. Upon TP excitation
      of QD-Ce6 solution, the fluorescence band of bound Ce6 molecules was observed via
      energy transfer from excited QDs. Increasing concentration of Ce6 resulted in
      quenching of the photoluminescence of QDs and an increase in the fluorescence
      intensity of bound Ce6 molecules. These intensity changes coincided well with
      those observed upon single-photon excitation of QD-Ce6 solution when QDs alone
      are excited. The efficiency of energy transfer in QD-Ce6 complex upon TP
      excitation was about 80% (QD?Ce61?5). These results indicate that the effective
      excitation of PS with a low TP absorption cross-section is possible in such type
      noncovalent complexes via energy transfer from TP excited QDs.

PMID- 23864018
TI  - Gene therapy for deafness.
AB  - Hearing loss is the most common sensory deficit in humans and can result from
      genetic, environmental or combined etiologies that prevent normal function of the
      cochlea, the peripheral sensory organ. Recent advances in understanding the
      genetic pathways that are critical for the development and maintenance of
      cochlear function, as well as the molecular mechanisms that underlie cell trauma
      and death, have provided exciting opportunities for modulating these pathways to
      correct genetic mutations, to enhance the endogenous protective pathways for
      hearing preservation and to regenerate lost sensory cells with the possibility of
      ameliorating hearing loss. A number of recent animal studies have used gene-based
      therapies in innovative ways toward realizing these goals. With further
      refinement, some of the protective and regenerative approaches reviewed here may
      become clinically applicable. 

PMID- 23864020
TI  - A migrated aortic stent graft causing erosive spondylopathy.
AB  - We report about a patient presenting with back pain 4 months after an uneventful
      endovascular implantation of an aortic stent graft. Computed tomography scan
      revealed a migration of the stent with consecutive endoleakage, kink formation,
      and movement of the stent toward the spine, which caused destruction of the
      aortic wall as well as vertebral necrosis. Explantation of the stent and
      replacement of the native aorta relieved the patient of his symptoms.

PMID- 23864019
TI  - A paradigm shift in trauma resuscitation: evaluation of evolving massive
      transfusion practices.
AB  - IMPORTANCE: The evolution of damage control strategies has led to significant
      changes in the use of resuscitation after traumatic injury. OBJECTIVE: To
      evaluate changes in the administration of fluids and blood products,
      hypothesizing that a reduction in crystalloid volume and a reduced red blood cell
      (RBC) to fresh frozen plasma (FFP) ratio over the last 7 years would correlate
      with better resuscitation outcomes. DESIGN: Observational prospective cohort
      study. SETTING: Urban level I trauma center. PARTICIPANTS: A total of 174 trauma
      patients receiving a massive transfusion (>10 units of RBCs in 24 hours) or
      requiring the activation of the institutional massive transfusion protocol from
      February 2005 to June 2011. EXPOSURE: Patients had to either receive a massive
      transfusion or require the activation of the institutional massive transfusion
      protocol. MAIN OUTCOMES AND MEASURES: In-hospital mortality. RESULTS: The mean
      (SD) Injury Severity Score was 28.4 (16.2), the mean (SD) base deficit was -9.8
      (6.3), and median international normalized ratio was 1.3 (interquartile range,
      1.2-1.6); the mortality rate was 40.8%. Patients received a median of 6.1 L of
      crystalloid, 13 units of RBCs, 10 units of FFP, and 1 unit of platelets over 24
      hours, with a mean RBC:FFP ratio of 1.58:1. The mean 24-hour crystalloid infusion
      volume and number of the total blood product units given in the first 24 hours
      decreased significantly over the study period (P < .05). The RBC:FFP ratio
      decreased from a peak of 1.84:1 in 2007 to 1.55:1 in 2011 (P = .20). Injury
      severity and mortality remained stable over the study period. When adjusted for
      age and injury characteristics using Cox regression, each decrease of 0.1
      achieved in the massive transfusion protocol's RBC:FFP ratio was associated with
      a 5.6% reduction in mortality (P = .005). CONCLUSIONS AND RELEVANCE: There has
      been a shift toward a reduced crystalloid volume and the recreation of whole
      blood from component products in resuscitation. These changes are associated with
      markedly improved outcomes and a new paradigm in the resuscitation of severely
      injured patients.

PMID- 23864021
TI  - Efficacy of TACE in TIPS patients: comparison of treatment response to
      chemoembolization for hepatocellular carcinoma in patients with and without a
      transjugular intrahepatic portosystemic shunt.
AB  - PURPOSE: To compare treatment response after transarterial chemoembolization
      (TACE) for hepatocellular carcinoma (HCC) in patients with and without a
      transjugular intrahepatic portosystemic shunt (TIPS). MATERIALS AND METHODS: A
      retrospective review of patients who underwent conventional TACE for HCC between
      January 2005 and December 2009 identified 10 patients with patent TIPS. From the
      same time period, 23 patients without TIPS were selected to control for
      comparable Model for End-Stage Liver Disease and Child-Pugh-Turcotte scores. The
      two groups showed similar distribution of Barcelona Clinic Liver Cancer and
      United Network of Organ Sharing stages. Target HCC lesions were evaluated
      according to the modified response evaluation criteria in solid tumors (mRECIST)
      guidelines. Transplantation rate, time to tumor progression, and overall survival
      (OS) were documented. RESULTS: After TACE, the rate of complete response was
      significantly greater in non-TIPS patients compared with TIPS patients (74 vs. 30
      %, p = 0.03). Objective response rate (complete and partial response) trended
      greater in the non-TIPS group (83 vs. 50 %, p = 0.09). The liver transplantation
      rate was 80 and 74 % in the TIPS and non-TIPS groups, respectively (p = 1.0).
      Time to tumor progression was similar (p = 0.47) between the two groups. OS
      favored the non-TIPS group (p = 0.01) when censored for liver transplantation.
      CONCLUSION: TACE is less effective in achieving complete or partial response
      using mRECIST criteria in TIPS patients compared with those without a TIPS.
      Nevertheless, similar clinical outcomes may be achieved, particularly in TIPS
      patients who are liver-transplantation candidates.

PMID- 23864023
TI  - Programming MOFs for water sorption: amino-functionalized MIL-125 and UiO-66 for
      heat transformation and heat storage applications.
AB  - Sorption-based heat transformation and storage appliances are very promising for
      utilizing solar heat and waste heat in cooling or heating applications. The
      economic and ecological efficiency of sorption-based heat transformation depends
      on the availability of suitable hydrophilic and hydrothermally stable sorption
      materials. We investigated the feasibility of using the metal-organic frameworks
      UiO-66(Zr), UiO-67(Zr), H2N-UiO-66(Zr) and H2N-MIL-125(Ti) as sorption materials
      in heat transformations by means of volumetric water adsorption measurements,
      determination of the heat of adsorption and a 40-cycle ad/desorption stress test.
      The amino-modified compounds H2N-UiO-66 and H2N-MIL-125 feature high heat of
      adsorption (89.5 and 56.0 kJ mol(-1), respectively) and a very promising H2O
      adsorption isotherm due to their enhanced hydrophilicity. For H2N-MIL-125 the
      very steep rise of the H2O adsorption isotherm in the 0.1 < p/p0 < 0.2 region is
      especially beneficial for the intended heat pump application. 

PMID- 23864025
TI  - A special issue about hepatotoxicity and hepatocyte in vitro systems.

PMID- 23864024
TI  - A physiologically based in silico model for trans-2-hexenal detoxification and
      DNA adduct formation in human including interindividual variation indicates
      efficient detoxification and a negligible genotoxicity risk.
AB  - A number of alpha,beta-unsaturated aldehydes are present in food both as natural
      constituents and as flavouring agents. Their reaction with DNA due to their
      electrophilic alpha,beta-unsaturated aldehyde moiety may result in genotoxicity
      as observed in some in vitro models, thereby raising a safety concern. A question
      that remains is whether in vivo detoxification would be efficient enough to
      prevent DNA adduct formation and genotoxicity. In this study, a human
      physiologically based kinetic/dynamic (PBK/D) model of trans-2-hexenal (2
      hexenal), a selected model alpha,beta-unsaturated aldehyde, was developed to
      examine dose-dependent detoxification and DNA adduct formation in humans upon
      dietary exposure. The kinetic model parameters for detoxification were quantified
      using relevant pooled human tissue fractions as well as tissue fractions from 11
      different individual subjects. In addition, a Monte Carlo simulation was
      performed so that the impact of interindividual variation in 2-hexenal
      detoxification on the DNA adduct formation in the population as a whole could be
      examined. The PBK/D model revealed that DNA adduct formation due to 2-hexenal
      exposure was 0.039 adducts/108 nucleotides (nt) at the estimated average 2
      hexenal dietary intake (0.04 mg 2-hexenal/kg bw) and 0.18 adducts/108 nt at the
      95th percentile of the dietary intake (0.178 mg 2-hexenal/kg bw) in the most
      sensitive people. These levels are three orders of magnitude lower than natural
      background DNA adduct levels that have been reported in disease-free humans (6.8
      110 adducts/108 nt), suggesting that the genotoxicity risk for the human
      population at realistic dietary daily intakes of 2-hexenal may be negligible.

PMID- 23864022
TI  - Hace1 controls ROS generation of vertebrate Rac1-dependent NADPH oxidase
      complexes.
AB  - The Hace1-HECT E3 ligase is a tumor suppressor that ubiquitylates the activated
      GTP-bound form of the Rho family GTPase Rac1, leading to Rac1 proteasomal
      degradation. Here we show that, in vertebrates, Hace1 targets Rac1 for
      degradation when Rac1 is localized to the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase holoenzyme. This event blocks de novo reactive oxygen
      species generation by Rac1-dependent NADPH oxidases, and thereby confers cellular
      protection from reactive oxygen species-induced DNA damage and cyclin D1-driven
      hyper-proliferation. Genetic inactivation of Hace1 in mice or zebrafish, as well
      as Hace1 loss in human tumor cell lines or primary murine or human tumors, leads
      to chronic NADPH oxidase-dependent reactive oxygen species elevation, DNA damage
      responses and enhanced cyclin D1 expression. Our data reveal a conserved
      ubiquitin-dependent molecular mechanism that controls the activity of Rac1
      dependent NADPH oxidase complexes, and thus constitutes the first known example
      of a tumor suppressor protein that directly regulates reactive oxygen species
      production in vertebrates. 

PMID- 23864026
TI  - One-pot, water-based and high-yield synthesis of tetrahedral palladium
      nanocrystal decorated graphene.
AB  - This paper reports a facile, water-based and one-pot synthesis of tetrahedral Pd
      nanocrystals (Pd-TNPs) with high yield and good size monodispersity supported on
      reduced graphene oxide (RGO) nanosheets via a co-chemical reduction method. The
      key synthetic strategy employed a positively charged polyallylamine-Pd(II)
      complex (PAH-Pd(II)) with un-coordinated amine groups as a linker molecule to
      immobilize Pd(II) species on the negatively charged graphene oxide (GO) surface
      through electrostatic interaction. As characterized by transmission electron
      microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD),
      Raman spectroscopy, thermogravimetric analysis (TGA), X-ray photoelectron
      spectroscopy (XPS) techniques, well-defined Pd-TNPs with an average size of 9 nm
      were uniformly distributed on the RGO surface. The as-prepared Pd-TNPs/RGO
      nanohybrid with excellent colloidal stability in aqueous solution exhibits
      superior catalytic activity towards the degradation of methylene blue (MB)
      compared to both unsupported Pd-TNPs and Pd black. Thus, the resultant Pd
      TNPs/RGO nanohybrid, as a promising heterogeneous catalyst, might have wide
      potential applications in water-based catalysis systems for the future. 

PMID- 23864028
TI  - Mechanochemistry of inorganic and organic systems: what is similar, what is
      different?
AB  - Mechanochemistry of inorganic solids is a well-established field. In the last
      decade mechanical treatment has become increasingly popular as a method for
      achieving selective and "greener" syntheses also in organic systems. New groups
      and researchers enter the field of mechanochemistry, often re-discovering many of
      the previously known facts and effects, while at the same time neglecting other
      important concepts. The author of this contribution has long been involved in
      mechanochemical research in both inorganic and organic systems. The aim of this
      contribution is to provide an overview of the basic concepts of mechanochemistry
      in relation to inorganic and organic systems. 

PMID- 23864029
TI  - Upregulation of gene expression in reward-modulatory striatal opioid systems by
      sleep loss.
AB  - Epidemiological studies have shown a link between sleep loss and the obesity
      'epidemic,' and several observations indicate that sleep curtailment engenders
      positive energy balance via increased palatable-food 'snacking.' These effects
      suggest alterations in reward-modulatory brain systems. We explored the effects
      of 10 days of sleep deprivation in rats on the expression of striatal opioid
      peptide (OP) genes that subserve food motivation and hedonic reward, and compared
      effects with those seen in hypothalamic energy balance-regulatory systems. Sleep
      deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus
      controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated
      controls (Home-Cage). Detection of mRNA levels with in situ hybridization
      revealed a subregion-specific upregulation of striatal preproenkephalin and
      prodynorhin gene expression in the Sleep-Dep group relative to all other groups.
      Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and
      throughout neocortex was also robustly upregulated selectively in the Sleep-Dep
      group. In contrast, parallel gene expression changes were observed in the Sleep
      Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate
      nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript
      was downregulated), in alignment with leptin suppression in both groups.
      Together, these results reveal a novel set of sleep deprivation-induced
      transcriptional changes in reward-modulatory peptide systems, which are
      dissociable from the energy-balance perturbations of sleep loss or the
      potentially stressful effects of the forced-locomotion procedure. The recruitment
      of telencephalic food-reward systems may provide a feeding drive highly resistant
      to feedback control, which could engender obesity through the enhancement of
      palatable feeding. 

PMID- 23864033
TI  - Human soluble guanylate cyclase as a nitric oxide sensor for NO-signalling
      reveals a novel function of nitrite reductase.
AB  - Human soluble guanylate cyclase (hsGC), a NO sensor/NO receptor of a
      heterodimeric hemoprotein, plays a critical role in the NO-sGC-cGMP signaling
      pathway, and also reveals a novel nitrite reductase activity. This indicates that
      hsGC could activate itself by catalytic reduction of nitrite to NO instead of
      receiving NO from nitric oxide synthase (NOS), which provides valuable insight
      into the physiological function of the homodimeric hsGC. 

PMID- 23864031
TI  - Mapping mammalian synaptic connectivity.
AB  - Mapping mammalian synaptic connectivity has long been an important goal of
      neuroscientists since it is considered crucial for explaining human perception
      and behavior. Yet, despite enormous efforts, the overwhelming complexity of the
      neural circuitry and the lack of appropriate techniques to unravel it have
      limited the success of efforts to map connectivity. However, recent technological
      advances designed to overcome the limitations of conventional methods for
      connectivity mapping may bring about a turning point. Here, we address the
      promises and pitfalls of these new mapping technologies. 

PMID- 23864032
TI  - Acyl-CoA thioesterase 9 (ACOT9) in mouse may provide a novel link between fatty
      acid and amino acid metabolism in mitochondria.
AB  - Acyl-CoA thioesterase (ACOT) activities are found in prokaryotes and in several
      compartments of eukaryotes where they hydrolyze a wide range of acyl-CoA
      substrates and thereby regulate intracellular acyl-CoA/CoA/fatty acid levels.
      ACOT9 is a mitochondrial ACOT with homologous genes found from bacteria to humans
      and in this study we have carried out an in-depth kinetic characterization of
      ACOT9 to determine its possible physiological function. ACOT9 showed unusual
      kinetic properties with activity peaks for short-, medium-, and saturated long
      chain acyl-CoAs with highest V max with propionyl-CoA and (iso) butyryl-CoA while
      K cat/K m was highest with saturated long-chain acyl-CoAs. Further
      characterization of the short-chain acyl-CoA activity revealed that ACOT9 also
      hydrolyzes a number of short-chain acyl-CoAs and short-chain methyl-branched CoA
      esters that suggest a role for ACOT9 in regulation also of amino acid metabolism.
      In spite of markedly different K ms, ACOT9 can hydrolyze both short- and long
      chain acyl-CoAs simultaneously, indicating that ACOT9 may provide a novel
      regulatory link between fatty acid and amino acid metabolism in mitochondria.
      Based on similar acyl-CoA chain-length specificities of recombinant ACOT9 and
      ACOT activity in mouse brown adipose tissue and kidney mitochondria, we conclude
      that ACOT9 is the major mitochondrial ACOT hydrolyzing saturated C2-C20-CoA in
      these tissues. Finally, ACOT9 activity is strongly regulated by NADH and CoA,
      suggesting that mitochondrial metabolic state regulates the function of ACOT9. 

PMID- 23864030
TI  - Therapeutic neuroprotective agents for amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease
      whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor
      neurons and surrounding cells. Multiple mechanisms proposed as responsible for
      ALS pathogenesis include dysfunction of protein degradation, glutamate
      excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and
      inflammation. It is therefore essential to gain a better understanding of the
      underlying disease etiology and search for neuroprotective agents that might
      delay disease onset, slow progression, prolong survival, and ultimately reduce
      the burden of disease. Because riluzole, the only Food and Drug Administration
      (FDA)-approved treatment, prolongs the ALS patient's life by only 3 months, new
      therapeutic agents are urgently needed. In this review, we focus on studies of
      various small pharmacological compounds targeting the proposed pathogenic
      mechanisms of ALS and discuss their impact on disease progression.

PMID- 23864034
TI  - Ethanol extract of Cnidium officinale exhibits anti-inflammatory effects in BV2
      microglial cells by suppressing NF-kappaB nuclear translocation and the
      activation of the PI3K/Akt signaling pathway.
AB  - Chronic microglial activation endangers neuronal survival through the release of
      various toxic pro-inflammatory molecules; thus, negative regulators of microglial
      activation have been identified as potential therapeutic candidates for several
      neurological diseases. In this study, we investigated the inhibitory effects of
      an ethanol extract of Cnidium officinale rhizomes (EECO), which has been used as
      a herbal drug in Oriental medicine, on the production of lipopolysaccharide (LPS)
      induced pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin
      E2 (PGE2), as well as that of pro-inflammatory cytokines in BV2 microglia cells.
      EECO significantly inhibited the excess production of NO and PGE2 in LPS
      stimulated BV2 microglia cells. It also attenuated the expression of inducible NO
      synthase, cyclooxygenase-2, as well as that of pro-inflammatory cytokines, such
      as interleukin-1beta and tumor necrosis factor-alpha. Moreover, EECO exhibited
      anti-inflammatory properties by suppressing nuclear factor-kappaB (NF-kappaB)
      translocation and the activation of the phosphoinositide 3-kinase/Akt pathway in
      LPS-stimulated BV2 cells. These results indicate that EECO exerts anti
      inflammatory effects in LPS-stimulated BV2 microglial cells by inhibiting pro
      inflammatory mediators and cytokine production by blocking the NF-kappaB pathway.
      These findings suggest that EECO has substantial therapeutic potential for the
      treatment of neurodegenerative diseases accompanied by microglial activation.

PMID- 23864035
TI  - Bortezomib and dexamethasone as salvage therapy in patients with
      relapsed/refractory multiple myeloma: analysis of long-term clinical outcomes.
AB  - Bortezomib (bort)-dexamethasone (dex) is an effective therapy for
      relapsed/refractory (R/R) multiple myeloma (MM). This retrospective study
      investigated the combination of bort (1.3 mg/m(2) on days 1, 4, 8, and 11 every 3
      weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment
      in 85 patients with R/R MM after prior autologous stem cell transplantation or
      conventional chemotherapy. The median number of prior lines of therapy was 2.
      Eighty-seven percent of the patients had received immunomodulatory drugs included
      in some line of therapy before bort-dex. The median number of bort-dex cycles was
      6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the
      patients achieved at least partial response, including 19 % CR and 35 % achieved
      at least very good partial response. Median durations of response, time to next
      therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively.
      The most relevant adverse event was peripheral neuropathy, which occurred in 78 %
      of the patients (grade II, 38 %; grade III, 21 %) and led to treatment
      discontinuation in 6 %. With a median follow up of 22 months, median time to
      progression, progression-free survival (PFS) and overall survival (OS) were 8.9,
      8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients
      achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was
      an effective salvage treatment for MM patients, particularly for those in first
      relapse.

PMID- 23864036
TI  - Multiphoton imaging microscopy at deeper layers with adaptive optics control of
      spherical aberration.
AB  - Despite the inherent confocality and optical sectioning capabilities of
      multiphoton microscopy, three-dimensional (3-D) imaging of thick samples is
      limited by the specimen-induced aberrations. The combination of immersion
      objectives and sensorless adaptive optics (AO) techniques has been suggested to
      overcome this difficulty. However, a complex plane-by-plane correction of
      aberrations is required, and its performance depends on a set of image-based
      merit functions. We propose here an alternative approach to increase penetration
      depth in 3-D multiphoton microscopy imaging. It is based on the manipulation of
      the spherical aberration (SA) of the incident beam with an AO device while
      performing fast tomographic multiphoton imaging. When inducing SA, the image
      quality at best focus is reduced; however, better quality images are obtained
      from deeper planes within the sample. This is a compromise that enables
      registration of improved 3-D multiphoton images using nonimmersion objectives.
      Examples on ocular tissues and nonbiological samples providing different types of
      nonlinear signal are presented. The implementation of this technique in a future
      clinical instrument might provide a better visualization of corneal structures in
      living eyes.

PMID- 23864037
TI  - Intracellular viscoelasticity of HeLa cells during cell division studied by video
      particle-tracking microrheology.
AB  - Cell division plays an important role in regulating cell proliferation and
      differentiation. It is managed by a complex sequence of cytoskeleton alteration
      that induces dividing cells to change their morphology to facilitate their
      division. The change in cytoskeleton structure is expected to affect the
      intracellular viscoelasticity, which may also contribute to cellular dynamic
      deformation during cell division. However, the intracellular viscoelasticity
      during cell division is not yet well understood. In this study, we injected 100
      nm (diameter) carboxylated polystyrene beads into the cytoplasm of HeLa cells and
      applied video particle tracking microrheology to measure their intracellular
      viscoelasticity at different phases during cell division. The Brownian motion of
      the intracellular nanoprobes was analyzed to compute the viscoelasticity of HeLa
      cells in terms of the elastic modulus and viscous modulus as a function of
      frequency. Our experimental results indicate that during the course of cell
      division, both intracellular elasticity and viscosity increase in the transition
      from the metaphase to the anaphase, plausibly due to the remodeling of
      cytoskeleton and redistributions of molecular motors, but remain approximately
      the same from the anaphase to the telophase.

PMID- 23864038
TI  - Ball milling: a green mechanochemical approach for synthesis of nitrogen doped
      carbon nanoparticles.
AB  - Technological and scientific challenges coupled with environmental considerations
      have attracted a search for robust, green and energy-efficient synthesis and
      processing routes for advanced functional nanomaterials. In this article, we
      demonstrate a high-energy ball milling technique for large-scale synthesis of
      nitrogen doped carbon nanoparticles, which can be used as an electro-catalyst for
      oxygen reduction reactions after a structural refinement with controlled thermal
      annealing. The resulting carbon nanoparticles exhibited competitive catalytic
      activity (5.2 mA cm(-2) kinetic-limiting current density compared with 7.6 mA cm(
      2) on Pt/C reference) and excellent methanol tolerance compared to a commercial
      Pt/C catalyst. The proposed synthesis route by ball milling and annealing is an
      effective process for carbon nanoparticle production and efficient nitrogen
      doping, providing a large-scale production method for the development of highly
      efficient and practical electrocatalysts. 

PMID- 23864039
TI  - Heart failure in a woman with SLE, anti-phospholipid syndrome and Fabry's
      disease.
AB  - We describe a female patient with systemic lupus erythematosus (SLE) also
      diagnosed with Fabry's disease and anti-phospholipid antibody syndrome (APS). SLE
      and Fabry's disease are both systemic diseases with variable clinical
      presentations. Recent studies have shown a relatively high incidence of late
      onset Fabry's disease in female heterozygous individuals, suggesting that this
      condition could be under-diagnosed. We discuss a possible association between SLE
      and Fabry's disease and consider the role of lipid abnormalities in the
      pathogenesis of SLE.

PMID- 23864041
TI  - NMR spectroscopic detection of chirality and enantiopurity in referenced systems
      without formation of diastereomers.
AB  - Enantiomeric excess of chiral compounds is a key parameter that determines their
      activity or therapeutic action. The current paradigm for rapid measurement of
      enantiomeric excess using NMR is based on the formation of diastereomeric
      complexes between the chiral analyte and a chiral resolving agent, leading to (at
      least) two species with no symmetry relationship. Here we report an effective
      method of enantiomeric excess determination using a symmetrical achiral molecule
      as the resolving agent, which is based on the complexation with analyte (in the
      fast exchange regime) without the formation of diastereomers. The use of N,N'
      disubstituted oxoporphyrinogen as the resolving agent makes this novel method
      extremely versatile, and appropriate for various chiral analytes including
      carboxylic acids, esters, alcohols and protected amino acids using the same
      achiral molecule. The model of sensing mechanism exhibits a fundamental linear
      response between enantiomeric excess and the observed magnitude of induced
      chemical shift non-equivalence in the (1)H NMR spectra. 

PMID- 23864042
TI  - Self-healing polymeric materials.
AB  - Inspired by nature, self-healing materials represent the forefront of recent
      developments in materials chemistry and engineering. This review outlines the
      recent advances in the field of self-healing polymers. The first part discusses
      thermodynamic requirements for self-healing networks in the context of
      conformation changes that contribute to the Gibbs free energy. The chain
      flexibility significantly contributes to the entropy changes, whereas the heat of
      reaction and the external energy input are the main contributors to enthalpy
      changes. The second part focuses on chemical reactions that lead to self-healing,
      and the primary classes are the covalent bonding, supramolecular assemblies,
      ionic interactions, chemo-mechanical self-healing, and shape memory polymers. The
      third part outlines recent advances using encapsulation, remote self-healing and
      the role of shape memory polymers. Recent developments in the field of self
      healing polymers undeniably indicate that the main challenge will be the
      designing of high glass transition (Tg) functional materials, which also exhibit
      stimuli-responsive attributes. Build-in controllable hierarchical
      heterogeneousness at various length scales capable of remote self-healing by
      physical and chemical responses will be essential in designing future materials
      of the 21st century. 

PMID- 23864043
TI  - Vanadium in inorganic chemistry: excerpts from the 8th International Vanadium
      Symposium.

PMID- 23864044
TI  - Contextual effects in interval-duration judgements in vision, audition and touch.
AB  - We examined the effect of temporal context on discrimination of intervals marked
      by auditory, visual and tactile stimuli. Subjects were asked to compare the
      duration of the interval immediately preceded by an irrelevant "distractor"
      stimulus with an interval with no distractor. For short interval durations, the
      presence of the distractor affected greatly the apparent duration of the test
      stimulus: short distractors caused the test interval to appear shorter and vice
      versa. For very short reference durations (<= 100 ms), the contextual effects
      were large, changing perceived duration by up to a factor of two. The effect of
      distractors reduced steadily for longer reference durations, to zero effect for
      durations greater than 500 ms. We found similar results for intervals defined by
      visual flashes, auditory tones and brief finger vibrations, all falling to zero
      effect at 500 ms. Under appropriate conditions, there were strong cross-modal
      interactions, particularly from audition to vision. We also measured the Weber
      fractions for duration discrimination and showed that under the conditions of
      this experiment, Weber fractions decreased steadily with duration, following a
      square-root law, similarly for all three modalities. The magnitude of the effect
      of the distractors on apparent duration correlated well with Weber fraction,
      showing that when duration discrimination was relatively more precise, the
      context dependency was less. The results were well fit by a simple Bayesian model
      combining noisy estimates of duration with the action of a resonance-like
      mechanism that tended to regularize the sound sequence intervals.

PMID- 23864045
TI  - Multiple conformations of 5-HT2A and 5-HT 2C receptors in rat brain: an
      autoradiographic study with [125I](+/-)DOI.
AB  - Earlier autoradiographic studies with the 5-HT2 receptor agonist [(125)I](+/-)DOI
      in human brain showed unexpected biphasic competition curves for various 5-HT2A
      antagonists. We have performed similar studies in rat brain regions with
      selective 5-HT2A (M100907) and 5-HT2C (SB242084) antagonists together with
      ketanserin and mesulergine. The effect of GTP analogues on antagonist competition
      was also studied. Increasing concentrations of Gpp(NH)p or GTPgammaS resulted in
      a maximal inhibition of [(125)I](+/-)DOI-specific binding of approximately 50 %.
      M100907 competed biphasically in all regions. In the presence of 100 MUM
      Gpp(NH)p, M100907 still displaced biphasically the remaining [(125)I](+/-)DOI
      binding. Ketanserin showed biphasic curves in some regions and monophasic curves
      in others. In the latter, Gpp(NH)p evidenced an additional high-affinity site.
      SB242084 competed biphasically in brainstem nuclei and monophasically in the
      other regions. In most areas, SB242084 affinities were not notably altered by
      Gpp(NH)p. Mesulergine competed monophasically in all regions without alteration
      by Gpp(NH)p. These results conform with the extended ternary complex model of
      receptor action: receptor exists as an equilibrium of multiple conformations,
      i.e. ground (R), partly activated (R*) and activated G-protein-coupled (R*G)
      conformation/s. Thus, [(125)I](+/-)DOI would label multiple conformations of both
      5-HT2A and 5-HT2C receptors in rat brain, and M100907 and ketanserin would
      recognise these conformations with different affinities. 

PMID- 23864046
TI  - Reacting while moving: influence of right limb movement on left limb reaction.
AB  - An experiment was designed to determine whether the activation of a muscle group
      (flexors or extensors) used to produce an ongoing movement of one limb influenced
      the reaction time and associated initiation of elbow flexion or extension
      movements of the contralateral limb. Right-handed participants in the bimanual
      groups were asked to produce a pattern of flexion/extension movements defined by
      a sine wave (period = 2 s, amplitude = 16 degrees ) with the right limb. While
      performing the right limb movement, participants were instructed that they were
      to react as quickly as possible by making a flexion or extension movement with
      their left limb when the cursor they were using to track the sine wave changed
      color. Participants in the unimanual groups performed the left limb reaction time
      task but were not asked to make right limb movements. The reaction time stimulus
      occurred once in each trial and was presented at one of six locations on one of
      the six cycles comprising the sinusoidal waveform. Participants performed 7
      blocks of 6 test trials. Reaction time was calculated as the time interval
      between the color change of the cursor and the initiation of the response with
      the left limb. Movement time was calculated as the interval of time between the
      initiation of the response and the left limb cursor crossing the upper or lower
      boundary line. Mean reaction of the left limb was significantly influenced by the
      concurrent type of movement (flexion/extension) of the right limb. Reaction times
      were shorter on trials in which both limbs were initiating movement with
      homologous muscles as compared to trials in which the limbs were initiating
      movement with non-homologous muscles. No differences were detected when the
      stimuli were presented during the ballistic phase of the right limb movement, and
      no differences at any position were detected for the unimanual groups. This
      result is consistent with the notion that neural crosstalk can influence the time
      required to react to a stimulus but this influence occurs when contralateral
      muscles are activated.

PMID- 23864047
TI  - Global processing during the Muller-Lyer illusion is distinctively affected by
      the degree of autistic traits in the typical population.
AB  - Earlier work examining susceptibility to visual illusions in autism has reported
      discrepant findings. Some of this research suggests that global processing is
      affected in autism while some of this research suggests otherwise. The
      discrepancies may relate to compliance issues and differences in population
      samples in terms of symptom severity, cognitive ability, and co-morbid disorders.
      Equally important, most of this work tended to treat global processing as if it
      were a singular construct, invoking similar cognitive operations across different
      visual illusions. We argue that this is not a fair assumption to make given the
      extensive research that has classified visual illusions on the basis of their
      cognitive demands. With this in mind, and to overcome the many caveats associated
      with examining a heterogeneous disorder such as autism directly, we examined how
      susceptibility to various illusions relates differently to people's scores on the
      Autism Spectrum Quotient (AQ) questionnaire. We found that susceptibility to the
      Muller-Lyer but not to the Ebbinghaus and Ponzo illusions decreased as a function
      of AQ and that the relationship between AQ and susceptibility to the Muller-Lyer
      illusion was different from those between AQ and susceptibility to the Ebbinghaus
      and Ponzo illusions. Our findings confirm that the cognitive operations
      underlying global processing in the Muller-Lyer illusion are different from the
      other illusions and, more importantly, reveal that they might be affected in
      autism. Future brain mapping studies could provide additional insight into the
      neural underpinnings of how global processing might and might not be affected in
      autism. 

PMID- 23864048
TI  - ["De-mutilating the Cripples". The Siemens-Schuckert-Prosthesis and Welfare for
      Disabled Soldiers in Germany during the First World War].

PMID- 23864049
TI  - The general surgery chief resident operative experience: 23 years of national
      ACGME case logs.
AB  - IMPORTANCE: The chief resident (CR) year is a pivotal experience in surgical
      training. Changes in case volume and diversity may impact the educational quality
      of this important year. OBJECTIVE: To evaluate changes in operative experience
      for general surgery CRs. DESIGN, SETTING, AND PARTICIPANTS: Review of
      Accreditation Council for Graduate Medical Education case logs from 1989-1990
      through 2011-2012 divided into 5 periods. Graduates in period 3 were the last to
      train with unrestricted work hours; those in period 4 were part of a transition
      period and trained under both systems; and those in period 5 trained fully under
      the 80-hour work week. Diversity of cases was assessed based on Accreditation
      Council for Graduate Medical Education defined categories. MAIN OUTCOMES AND
      MEASURES: Total cases and defined categories were evaluated for changes over
      time. RESULTS: The average total CR case numbers have fallen (271 in period 1 vs
      242 in period 5, P < .001). Total CR cases dropped to their lowest following
      implementation of the 80-hour work week (236 cases), but rebounded in period 5.
      The percentage of residents' 5-year operative experience performed as CRs has
      decreased (30% in period 1 vs 25.6% in period 5, P < .001). Regarding case mix:
      thoracic, trauma, and vascular cases declined steadily, while alimentary and
      intra-abdominal operations increased. Recent graduates averaged 80 alimentary and
      78 intra-abdominal procedures during their CR years. Compared with period 1, in
      which these 2 categories represented 47.1% of CR experience, in period 5, they
      represented 65.2% (P < .001). Endocrine experience has been relatively unchanged.
      CONCLUSIONS AND RELEVANCE: Total CR cases declined especially acutely following
      implementation of the 80-hour work week but have since rebounded. Chief resident
      cases contribute less to overall experience, although this proportion stabilized
      before the 80-hour work week. Case mix has narrowed, with significant increases
      in alimentary and intra-abdominal cases. Broad-based general surgery training may
      be jeopardized by reduced case diversity. Chief resident cases are crucial in
      surgical training and educators should consider these findings as surgical
      training evolves.

PMID- 23864051
TI  - Metastasis: Exit this way.

PMID- 23864052
TI  - Cancer stem cells: Easily moulded.

PMID- 23864053
TI  - Mechano-isomerization of azobenzene.
AB  - We show that ultrasound-induced mechanical force isomerizes an azobenzene
      centered within a poly(methyl acrylate) polymer from cis to trans configuration
      without cleaving the azo bond. The isomerization rate was not altered by the
      polarity of the solvent indicating that the isomerization occurs through a non
      polar, inversion transition state. 

PMID- 23864050
TI  - The role of engineering approaches in analysing cancer invasion and metastasis.
AB  - In the past decade, novel materials, probes and tools have enabled fundamental
      and applied cancer researchers to take a fresh look at the complex problem of
      tumour invasion and metastasis. These new tools, which include imaging
      modalities, controlled but complex in vitro culture conditions, and the ability
      to model and predict complex processes in vivo, represent an integration of
      traditional with novel engineering approaches; and their potential effect on
      quantitatively understanding tumour progression and invasion looks promising.

PMID- 23864055
TI  - Regulation of the sympathetic nervous system by nitric oxide and oxidative stress
      in the rostral ventrolateral medulla: 2012 Academic Conference Award from the
      Japanese Society of Hypertension.
AB  - Sympathoexcitation has an important role in the pathogenesis of hypertension.
      Previous studies have demonstrated that nitric oxide (NO) and/or oxidative stress
      in the brain are important for the regulation of the sympathetic nervous system.
      We have investigated the role of NO derived from an overexpression of endothelial
      NO synthase (eNOS) or oxidative stress in the rostral ventrolateral medulla
      (RVLM), which is known as a vasomotor center in the brainstem, on the regulation
      of the sympathetic nervous system. Our results indicated that NO derived from an
      overexpression of eNOS in the RVLM caused sympathoinhibition via an increase in
      gamma-amino butyric acid and that angiotensin II type 1 receptor (AT1R)-induced
      oxidative stress in the RVLM caused sympathoexcitation. We also demonstrated that
      oxidative stress in the RVLM caused sympathoexcitation via interactions with NO,
      effects on the signal transduction or apoptosis of the astrocytes. Furthermore,
      several orally administered AT1R blockers have been found to cause
      sympathoinhibition via a reduction in oxidative stress through the blockade of
      AT1R in the RVLM of hypertensive rats. In conclusion, our studies suggest that
      the increase in AT1R-induced oxidative stress and/or the decrease in NO in the
      RVLM mainly cause sympathoexcitation in hypertension. 

PMID- 23864056
TI  - Effect of aldosterone breakthrough on albuminuria during treatment with a direct
      renin inhibitor and combined effect with a mineralocorticoid receptor antagonist.
AB  - We have reported observing aldosterone breakthrough in the course of relatively
      long-term treatment with renin-angiotensin (RA) system inhibitors, where the
      plasma aldosterone concentration (PAC) increased following an initial decrease.
      Aldosterone breakthrough has the potential to eliminate the organ-protective
      effects of RA system inhibitors. We therefore conducted a study in essential
      hypertensive patients to determine whether aldosterone breakthrough occurred
      during treatment with the direct renin inhibitor (DRI) aliskiren and to ascertain
      its clinical significance. The study included 40 essential hypertensive patients
      (18 men and 22 women) who had been treated for 12 months with aliskiren.
      Aliskiren significantly decreased blood pressure and plasma renin activity (PRA).
      The PAC was also decreased significantly at 3 and 6 months; however, the
      significant difference disappeared after 12 months. Aldosterone breakthrough was
      observed in 22 of the subjects (55%). Urinary albumin excretion differed
      depending on whether breakthrough occurred. For the subjects in whom aldosterone
      breakthrough was observed, eplerenone was added. A significant decrease in
      urinary albumin excretion was observed after 1 month, independent of changes in
      blood pressure. In conclusion, this study demonstrated that aldosterone
      breakthrough occurs in some patients undergoing DRI therapy. Aldosterone
      breakthrough affects the drug's ability to improve urinary albumin excretion, and
      combining a mineralocorticoid receptor antagonist with the DRI may be useful for
      decreasing urinary albumin excretion. When the objective is organ protection in
      hypertensive patients, a two-pronged approach using combination therapy to
      inhibit both the RA system and aldosterone may be highly effective. 

PMID- 23864057
TI  - Changes in aldosterone and obesity-related cardiometabolic risk factors with a 1
      year weight loss intervention in normotensive overweight and obese young adults.

PMID- 23864059
TI  - CMR assessment of right ventricular function in patients with combined pulmonary
      stenosis and insufficiency after correction of tetralogy of Fallot.
AB  - BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common types of
      congenital heart disease and requires prompt surgical correction. Post-correction
      pulmonary insufficiency (PI) often ensues in adulthood. At times, the PI is
      accompanied by residual pulmonary stenosis (PS). Little is known regarding right
      ventricular (RV) function in the setting of combined PS and PI. PURPOSE: To
      compare cardiac magnetic resonance (CMR) parameters for the assessment of RV
      function between patients with combined pulmonary stenosis and pulmonary
      insufficiency (PSPI) and isolated PI following surgical repair of TOF. MATERIAL
      AND METHODS: Retrospective review of patients with comparable corrected TOF and
      similar PI was performed. Seventeen patients (median age, 24 years; range, 10-52
      years) had combined PSPI and 30 patients (median age, 30 years; range, 6-70
      years) had isolated PI. Cine magnetic resonance (MR) images (Philips Medical
      Systems, Best, The Netherlands) in the short-axis plane were used to calculate
      end-systolic, end-diastolic, and stroke volumes (RVESV, RVEDV, RVSV) and to
      measure RV wall thickness. Velocity-encoded cine MR images were used to measure
      pulmonary regurgitation fraction (PRF) by calculating the ratio of backward flow
      and total forward flow, obtained from the main pulmonary flow analysis. Peak
      pressure gradient across the pulmonary valve was obtained from spectral Doppler
      echocardiography. RESULTS: RVEF was 51 +/- 8% in the PSPI patients and 39 +/-
      11%, in the patients with isolated PI (P = 0.001). Additionally, RV wall
      thickness was 5.2 +/- 0.8 mm in the PSPI patients compared to 2.6 +/- 0.9 mm in
      the isolated PI patients (P = 0.001). RVESVi and RVEDVi were significantly lower
      (P < 0.05) in patients with combined PSPI (60 +/- 21 mL/m(2), 121 +/- 35 mL/m(2),
      respectively) compared to the patients with isolated PI (95 +/- 48 mL/m(2), 152
      +/- 61 mL/m(2), respectively). CONCLUSION: RV function is preserved in patients
      with PSPI when compared to patients with PI following surgical repair of TOF.

PMID- 23864060
TI  - The contribution of diffusion tensor imaging and magnetic resonance spectroscopy
      for the differentiation of breast lesions at 3T.
AB  - BACKGROUND: Conventional breast magnetic resonance imaging (MRI), including
      dynamic contrast-enhanced MR mammography (DCE-MRM), may lead to ambiguous
      diagnosis and unnecessary biopsies. PURPOSE: To investigate the contribution of
      proton MR spectroscopy (1H-MRS) combined with diffusion tensor imaging (DTI)
      metrics in the discrimination between benign and malignant breast lesions.
      MATERIAL AND METHODS: Fifty-one women with known breast abnormalities from
      conventional imaging were examined on a 3T MR scanner. DTI was performed during
      breast MRI, and fractional anisotropy (FA) and apparent diffusion coefficient
      (ADC) were measured in the breast lesions and the contralateral normal breast. FA
      and ADC were compared between malignant lesions, benign lesions, and normal
      tissue. 1H-MRS was performed after gadolinium administration and choline peak was
      qualitatively evaluated. RESULTS: In our study 1H-MRS showed a sensitivity of
      93.5%, specificity 80%, and accuracy 88.2%. FA was significantly higher in breast
      carcinomas compared to benign lesions. However, no significant difference was
      observed in ADC between benign and malignant lesions. The combination of Cho
      presence and FA achieved higher levels of accuracy and specificity in
      discriminating malignant from benign lesions over Cho presence or FA alone.
      CONCLUSION: In conclusion, applying DTI and 1H-MRS together, adds incremental
      diagnostic value in the characterization of breast lesions and may sufficiently
      improve the low specificity of conventional breast MRI.

PMID- 23864061
TI  - Pulmonary embolism in oncologic patients: frequency and embolus burden of
      symptomatic and unsuspected events.
AB  - BACKGROUND: Pulmonary embolism (PE) is a common cause of morbidity and mortality
      in oncologic patients. Furthermore, PE is an unsuspected finding in many cases.
      PURPOSE: To determine the frequency and embolus burden of PE in a consecutive
      oncologic patient group including symptomatic as well as incidental and initially
      unreported events. MATERIAL AND METHODS: In a retrospective, single-center study
      from June 2005 to January 2010 all patients with an oncologic disease (ICD-10
      code C00 to C96) that received at least one contrast-enhanced computed tomography
      (CT) examination of the chest were reviewed. The study group included 3270
      patients with 6780 examinations. A validated pulmonary artery obstruction index
      (Mastora score) was used to assess embolus burden. RESULTS: PE was found in 240
      of 3270 (7.3%) oncologic patients. The frequency was highly variable among
      different malignancies ranging from 0% to 25%. In the present study about half of
      all PE were unsuspected. The mean embolus burden was significantly higher in
      symptomatic PE than in unsuspected PE (P <0.001). The risk of developing a PE was
      1.5 times higher in patients with metastases compared to patients without
      metastases (P <0.005). Age and sex had no influence on PE risk and embolus
      burden. CONCLUSION: PE is a frequent unsuspected finding in staging examinations:
      particularly in patients with malignancies of the ovary, brain, and pancreas, and
      in patients with metastases. Therefore, the status of the pulmonary vasculature
      should be assessed in every staging examination that includes the chest. The
      effect of therapeutic actions on PE events and the unsuspected finding of PE in
      follow-up CT examinations require further prospective studies.

PMID- 23864062
TI  - MDCT-based scoring system for differentiating angiomyolipoma with minimal fat
      from renal cell carcinoma.
AB  - BACKGROUND: Subtype-related various computed tomography (CT) features of renal
      cell carcinoma (RCC) are a confusing factor in differentiating angiomyolipoma
      with minimal fat (AMLmf) from RCC. To overcome RCC heterogeneity, a scoring
      system, which integrates multiple discrimitive parameters can be helpful for
      differentiating AMLmf from RCC. PURPOSE: To develop a MDCT-based scoring system
      for differentiating AMLmf from RCC. MATERIAL AND METHODS: In 407 patients with
      pathologically confirmed 48 AMLmfs and 359 RCCs (247 clear cell RCCs, 67
      papillary RCCs, and 45 chromophobe RCCs), MDCT features (ratio of long-to-short
      diameter, enhancement characteristics, tumor attenuation on unenhanced scan,
      tumor margin, calcification), age, and sex were compared between AMLmf and RCCs.
      Based on logistic regression, a scoring system for diagnosing AMLmf over RCC was
      built, and its diagnostic accuracy was evaluated. RESULTS: Scores suggesting
      AMLmf, i.e. the logit function as used in logistic regression analysis, were
      calculated as follows: Score = e(6.16.A-0.003.B+1.20.C+0.97.D+2.13.E
      0.05.F)/1+e(6.16.A-0.003.B+1.20.C+0.97.D+2.13.E-0.05.F), where A = ratio of long
      to-short diameter, B = enhancement amount in early excretory phase, C =
      homogeneous enhancement, D = tumor attenuation on unenhanced scan, E = sex, and F
      = age. Area under receiver-operating characteristics curve of scoring system was
      0.919. With a score of 0.204 or higher, the scoring system yielded greatest
      accuracy (90%, 368/407) for diagnosing AMLmf over RCC, which was greater than
      that of any single MDCT or clinical parameter (53-85%) (P < 0.05). With a score
      of 0.317 or higher, sensitivity and specificity were 68% (32/48) and 95%
      (340/359). CONCLUSION: MDCT-based scoring system can improve diagnostic
      performance of MDCT in differentiating AMLmf from RCC and help patients with
      AMLmf to avoid unnecessary surgery with high specificity.

PMID- 23864063
TI  - Volumetric analysis of lung nodules in computed tomography (CT): comparison of
      two different segmentation algorithm softwares and two different reconstruction
      filters on automated volume calculation.
AB  - BACKGROUND: A precise detection of volume change allows for better estimating the
      biological behavior of the lung nodules. Postprocessing tools with automated
      detection, segmentation, and volumetric analysis of lung nodules may expedite
      radiological processes and give additional confidence to the radiologists.
      PURPOSE: To compare two different postprocessing software algorithms (LMS Lung,
      Median Technologies; LungCARE(r), Siemens) in CT volumetric measurement and to
      analyze the effect of soft (B30) and hard reconstruction filter (B70) on
      automated volume measurement. MATERIAL AND METHODS: Between January 2010 and
      April 2010, 45 patients with a total of 113 pulmonary nodules were included. The
      CT exam was performed on a 64-row multidetector CT scanner (Somatom Sensation,
      Siemens, Erlangen, Germany) with the following parameters: collimation, 24x1.2
      mm; pitch, 1.15; voltage, 120 kVp; reference tube current-time, 100 mAs.
      Automated volumetric measurement of each lung nodule was performed with the two
      different postprocessing algorithms based on two reconstruction filters (B30 and
      B70). The average relative volume measurement difference (VME%) and the limits of
      agreement between two methods were used for comparison. RESULTS: At soft
      reconstruction filters the LMS system produced mean nodule volumes that were
      34.1% (P < 0.0001) larger than those by LungCARE(r) system. The VME% was 42.2%
      with a limit of agreement between -53.9% and 138.4%.The volume measurement with
      soft filters (B30) was significantly larger than with hard filters (B70); 11.2%
      for LMS and 1.6% for LungCARE(r), respectively (both with P < 0.05). LMS measured
      greater volumes with both filters, 13.6% for soft and 3.8% for hard filters,
      respectively (P < 0.01 and P > 0.05). CONCLUSION: There is a substantial inter
      software (LMS/LungCARE(r)) as well as intra-software variability (B30/B70) in
      lung nodule volume measurement; therefore, it is mandatory to use the same
      equipment with the same reconstruction filter for the follow-up of lung nodule
      volume.

PMID- 23864064
TI  - Role of combined BI-RADS assessment using mammography and sonography for
      evaluation of incidental hypermetabolic lesions in the breast on 18F-FDG PET-CT.
AB  - BACKGROUND: PET-CT is widely used for evaluation and follow-up of malignancy.
      Incidental hypermetabolic lesions are often found on PET-CT, some of which are
      confirmed to be malignant. PURPOSE: To estimate the role of combined Breast
      Imaging-Reporting and Data System (BI-RADS) assessment using mammography and
      sonography for evaluation of incidental hypermetabolic lesions on 18F-FDG PET-CT
      and to determine an appropriate next step. MATERIAL AND METHODS: This study
      included incidental hypermetabolic lesions found in the breasts of 7594 women who
      underwent PET-CT at three university-affiliated hospitals between January 2006
      and December 2011. We reviewed the maximum standardized uptake value (SUVmax) of
      incidental lesions, combined BI-RADS assessment of mammography and sonography,
      and final results. We analyzed the negative predictive values of the probably
      benign (categories 1-3) group and the sensitivity of suspicious (categories 4 and
      5) groups according to combined BI-RADS assessment. RESULTS: Forty-three patients
      (0.6%) had 49 incidental hypermetabolic lesions in the breast. Histologic
      diagnosis in 17 patients confirmed nine breast cancers (27.3%). Sixteen patients
      underwent imaging follow-up for at least 2 years; no breast cancer was detected.
      Thirteen patients were lost to follow-up and were excluded. For the suspicious (n
      = 14) and probably benign (n = 19) groups according to combined BI-RADS
      assessment, both the sensitivity and negative predictive values were 100%. Using
      an optimal diagnostic cut-off value of 2.15, the malignancy rate was not
      significantly different (16.7% vs. 45.5%, respectively, in the group with SUVmax
      < 2.15 and the group with SUVmax >= 2.15; P > 0.05). The SUVmax of the confirmed
      malignant and assumed benign groups were not significantly different (3.1% vs.
      2.2%, respectively; P > 0.05). CONCLUSION: Both mammography and sonography should
      be considered the next step to evaluate incidental hypermetabolic lesions on 18F
      FDG PET-CT because combined BI-RADS assessment provides an excellent negative
      predictive value for excluding malignancy.

PMID- 23864065
TI  - Acute prevertebral calcific tendinitis: a source of non-surgical acute cervical
      pain.
AB  - BACKGROUND: Prevertebral calcific tendinitis results from calcium hydroxyapatite
      crystal deposits in the longus colli muscles, which induce symptoms similar to
      some surgically-treated conditions, such as retropharyngeal abscesses. Imaging
      techniques are critical for accurate diagnosis. PURPOSE: To describe the computed
      tomography (CT) findings associated with prevertebral calcific tendinitis.
      MATERIAL AND METHODS: Retrospective analysis performed in an 18-month period,
      searching for patients with neck CT and reports with diagnosis of "calcific
      longus collis tendinitis" or "prevertebral calcific tendinitis". CT images and
      clinical data available in the medical records were analyzed. RESULTS: One
      hundred and thirty-four examinations were performed in the period studied. Nine
      patients who fulfilled inclusion criteria were identified and their CT imaging
      characteristics are presented. Six presented with calcific deposits in the right
      longus colli muscle. CT matched the clinical pain lateralization in all cases.
      Eight patients had no significant enhancement post injection of contrast media.
      CONCLUSION: Prevertebral calcific tendinitis is a cause of acute cervical pain
      that clinically mimics a retropharyngeal abscess, however on neck CT has a
      characteristic appearance. Correct identification of this pathologic condition
      will help avoiding unnecessary invasive procedures.

PMID- 23864066
TI  - Correlation between anatomic landmarks and fMRI in detection of the sensorimotor
      cortex in patients with structural lesions.
AB  - BACKGROUND: Structural lesions in/near the sensorimotor cortex may cause
      distortion/obscuration of the anatomic landmarks. PURPOSE: To compare the
      localization of the sensorimotor cortex using anatomical landmarks and fMRI in
      the clinical setting in patients with structural lesions in/near the central
      sulcus. MATERIAL AND METHODS: We analyzed the anatomic and fMRI data of 68
      consecutive patients (42 tumors, 15 gliotic lesions, 11 focal cortical dysplasias
      [FCD]) who underwent MRI to assess the relationship of these lesions to the
      sensorimotor cortex. Anatomical data was analyzed on conventional two- and three
      dimensional sequences. BOLD fMRI was performed with block design hand/leg or lip
      movement paradigm and general linear model was used for detecting the activated
      cortex. fMRI was considered as a valid method for identifying the sensorimotor
      cortex based on previously reported literature. RESULTS: The sensorimotor cortex
      could not be identified with anatomical landmarks in 9/68 (13.2%) patients. fMRI
      detected activation in areas different from that predicted by anatomical
      landmarks in 11/68 (16.2%) cases. This occurred in 5/42 (11.9%) tumors, 6/15
      (40%) gliotic lesions, and 0/11 (0%) FCDs. The kappa value for concordance
      between fMRI and anatomic landmarks was 0.883 overall, 1.0 for tumors, 0.721 for
      gliotic lesions, and in none of the patients with focal cortical dysplasias.
      CONCLUSION: In patients with lesions that obscure normal cerebral landmarks, fMRI
      supplies the information that is not available from the anatomic images. In
      patients with landmarks that can be recognized, the location of the rolandic
      cortex may be misjudged in some cases if functional imaging is not used. Anatomic
      landmarks may not correlate with the area of functional activation in gliotic
      lesions and tumors. Determining the risk of a postoperative neurologic defect
      from surgery is likely to be more reliable with functional imaging than with
      conventional anatomic imaging.

PMID- 23864058
TI  - Macrophages in tuberculosis: friend or foe.
AB  - Tuberculosis (TB) remains one of the greatest threats to human health. The
      causative bacterium, Mycobacterium tuberculosis (Mtb), is acquired by the
      respiratory route. It is exquisitely human adapted and a prototypic intracellular
      pathogen of macrophages, with alveolar macrophages (AMs) being the primary
      conduit of infection and disease. The outcome of primary infection is most often
      a latently infected healthy human host, in whom the bacteria are held in check by
      the host immune response. Such individuals can develop active TB later in life
      with impairment in the immune system. In contrast, in a minority of infected
      individuals, the host immune response fails to control the growth of bacilli, and
      progressive granulomatous disease develops, facilitating spread of the bacilli
      via infectious aerosols coughed out into the environment and inhaled by new
      hosts. The molecular details of the Mtb-macrophage interaction continue to be
      elucidated. However, it is clear that a number of complex processes are involved
      at the different stages of infection that may benefit either the bacterium or the
      host. Macrophages demonstrate tremendous phenotypic heterogeneity and functional
      plasticity which, depending on the site and stage of infection, facilitate the
      diverse outcomes. Moreover, host responses vary depending on the specific
      characteristics of the infecting Mtb strain. In this chapter, we describe a
      contemporary view of the behavior of AMs and their interaction with various Mtb
      strains in generating unique immunologic lung-specific responses. 

PMID- 23864067
TI  - India signals crackdown on dubious fixed dose drug combinations.

PMID- 23864068
TI  - Number of animal experiments in the UK rises by 8%.

PMID- 23864069
TI  - Developing and testing theory-based and evidence-based interventions to promote
      switching to arsenic-safe wells in Bangladesh.
AB  - Millions of people in Bangladesh drink arsenic-contaminated water despite
      increased awareness of consequences to health. Theory-based and evidence-based
      interventions are likely to have greater impact on people switching to existing
      arsenic-safe wells than providing information alone. To test this assumption, we
      first developed interventions based on an empirical test of the Risk, Attitudes,
      Norms, Abilities and Self-regulation (RANAS) model of behaviour change. In the
      second part of this study, a cluster-randomised controlled trial revealed that in
      accordance with our hypotheses, information alone showed smaller increases in
      switching to arsenic-safe wells than information with reminders or information
      with reminders and implementation intentions. 

PMID- 23864070
TI  - Affect mediates the association between mental adjustment styles and quality of
      life among Chinese cancer survivors.
AB  - This study examined the association between mental adjustment styles and quality
      of life, and affect as a mediator among 238 Chinese cancer survivors. Regression
      analysis showed that quality of life was positively associated with fighting
      spirit and negatively associated with fatalism. Path analysis showed that greater
      fighting spirit was associated with more positive affect, which in turn was
      associated with higher quality of life. Greater fatalism was associated with less
      positive affect and more negative affect, which in turn was associated with lower
      quality of life. Findings suggest that positive affect and negative affect are
      important in understanding mental adjustment styles and its health implications. 

PMID- 23864071
TI  - Perceptions of cancer as a death sentence: prevalence and consequences.
AB  - Research suggests that perceiving cancer as a death sentence is a critical
      determinant of health care-seeking behaviors. However, there is limited
      information regarding the prevalence of this perception in the US population.
      Cross-sectional analysis of data (n = 7674 adults) from the 2007-2008
      administration of the nationally representative Health Information National
      Trends Survey (HINTS 3) was performed. A majority (61.6%) of respondents
      perceived cancer as death sentence, and more than one-third (36%) of respondents
      reported that they avoid seeing their physicians. In the adult US population,
      perceiving cancer as a death sentence is common and is associated with education
      level and avoidance of physicians. 

PMID- 23864072
TI  - Examining patterns of association with defensive information processing about
      colorectal cancer screening.
AB  - To reduce negative psychological affect from information or behavior that is
      inconsistent with one's positive self-concept, individuals use a variety of
      defensive strategies. It is unknown whether correlates differ across defenses. We
      examined correlates of four levels of defensive information processing about
      colorectal cancer screening. Cross-sectional surveys were completed by a
      convenience sample of 287 adults aged 50-75 years. Defenses measures were more
      consistently associated with individual differences (especially avoidant coping
      styles); however, situational variables involving health-care providers also were
      important. Future research should examine changes in defenses after risk
      communication and their relative impact on colorectal cancer screening. 

PMID- 23864074
TI  - Clinician styles of care: transforming patient care at the intersection of
      leadership and medicine.
AB  - A key role of clinicians is to motivate their patients to initiate and maintain
      beneficial health behaviors. This article integrates research on transformational
      leadership, clinician-patient communication, and health behavior to introduce a
      novel approach to understanding and improving clinicians' effectiveness as
      motivators. We describe three dominant clinician styles or patterned approaches
      to patient care that derive from leadership theory (in order of least to most
      effective): laissez-faire, transactional, and transformational. Additionally, we
      suggest potential mediators and effects of the transformational style of care.
      Finally, we discuss future research directions for the study of clinician styles
      of care. 

PMID- 23864073
TI  - Difficult encounters with a hemophilic patient: the inner perspective of
      physicians.
AB  - This study aimed at exploring the hematologists' internal representation of a
      difficult encounter with a hemophilic patient, using a written open format.
      Narrations were analyzed with Interpretative Phenomenological Analysis. Three
      main issues were identified, each with sub-issues: (1) Inside the relationship:
      to tell or not to tell, the balance between a normal life and a deviant medical
      condition, the guilt; (2) The borders of the professional role: professional
      values, the "do-it-all" doctor; and (3) The existential confrontation. This study
      reveals the deep involvement of physicians with their patients, at a professional
      level and, strongly, at a personal level. The experience of being so deeply
      involved should be considered in the continuing medical programs for physicians
      dealing with hemophilia. 

PMID- 23864075
TI  - When do next-of-kin opt-in? Anticipated regret, affective attitudes and donating
      deceased family member's organs.
AB  - This research assessed whether affective factors promote and prevent family
      members from donating their loved one's organs. Participants (N = 191) imagined
      that a family member had died and that they had to decide whether or not to
      donate their organs and body parts for transplantation purposes. The least organs
      and body parts were donated when the deceased opposed donation. Moreover,
      participants who were not registered organ donors donated fewer organs than
      registered donors. This effect was mediated by anticipated regret, disgust and
      the perceived benefits of donation. Organ donation campaigns should target such
      factors to increase donor rates. 

PMID- 23864076
TI  - Self-esteem and quality of life of people living with HIV/AIDS.
AB  - In India in 2009, it was estimated that 2.4 million people were living with HIV,
      which equates to a prevalence of 0.3 percent. While this seems low, because
      India's population is so large, this rate is third in the world in terms of the
      absolute number of people living with HIV/AIDS. This study evaluated the self
      esteem and quality of life of people living with HIV/AIDS in the Indian
      population using a correlational design. A significant positive correlation
      between self esteem and the different dimensions of quality of life was
      established. Interventions designed for people with HIV/AIDS could well include
      self esteem as a moderator of quality of life. 

PMID- 23864077
TI  - Manipulating light absorption of graphene using plasmonic nanoparticles.
AB  - We present the incorporation of periodic gold nanoparticle arrays into graphene
      based photodetectors to enhance and tune light absorption of graphene. By the use
      of electromagnetic simulations, we show that light absorption in graphene can be
      manipulated by tuning plasmonic resonance. A maximum absorption of 30.3% with a
      full width of 135 nm at half maximum is achieved through systematic optimization
      of nanostructures. 

PMID- 23864079
TI  - Approaching erectile dysfunction in dermatology patients.

PMID- 23864081
TI  - T. C. Boyle, the ozone hole, skin cancer, and blindness.

PMID- 23864082
TI  - Saxophone penis.

PMID- 23864083
TI  - Measuring impact of JAMA Dermatology Practice Gaps section on training in US
      dermatology residency programs.
AB  - IMPORTANCE: JAMA Dermatology Practice Gaps commentaries are intended to aid in
      the interpretation of the literature to make it more practical and applicable to
      daily patient care. Practice Gaps commentaries have had an impact on physician
      clinical practice and dermatology residency curricula. OBJECTIVE: To assess the
      impact of JAMA Dermatology Practice Gaps commentaries on dermatology residency
      training programs in the United States, including journal club discussions and
      local quality improvement activities. DESIGN, SETTING, PARTICIPANTS: A web-based
      questionnaire of 17 questions was sent via e-mail to US dermatology residency
      program directors (PDs) in February 2012. MAIN OUTCOMES AND MEASURES: Program
      director report of incorporating Practice Gaps themes and discussions into
      resident journal club activities, clinical practice, quality improvement
      activities, or research projects in the residency programs, as a result of a
      Practice Gaps commentary. RESULTS: Of the 114 surveys distributed to US
      dermatology residency PDs, 48 were completed (42% response rate). Sixty percent
      of PDs reported familiarity with the Practice Gaps section of JAMA Dermatology,
      and 56% discuss these commentaries during resident journal club activities.
      Quality improvement and research projects have been initiated as a result of
      Practice Gaps commentaries. CONCLUSIONS AND RELEVANCE: Practice Gaps commentaries
      are discussed during most dermatology residency journal club activities. Practice
      Gaps have had an impact on physician practice and dermatology residency curricula
      and can serve as a tool for enhanced continuing medical education and quality
      improvement initiatives.

PMID- 23864085
TI  - Effect of radiation therapy on survival in patients with resected Merkel cell
      carcinoma: a propensity score surveillance, epidemiology, and end results
      database analysis.
AB  - IMPORTANCE: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignant
      neoplasm that can be highly aggressive and ultimately lethal. However, the
      cumulatively low incidence rate has made it difficult to accrue patients to
      prospective randomized trials. OBJECTIVE: To determine whether patients with MCC
      in the Surveillance, Epidemiology, and End Results (SEER) database who received
      radiation therapy after resection demonstrate improved survival. DESIGN: The
      study population consisted of SEER patients with histologically confirmed MCC who
      underwent surgical resection between January 1, 1998, and December 30, 2006. Cox
      proprotional hazards regression models were used to determine factors associated
      with MCC-specific and overall survival. Propensity scoring with matched pairs was
      used to perform Kaplan-Meier survival analysis comparing patients who underwent
      surgery plus radiation therapy vs those who underwent surgery alone. SETTING AND
      PARTICIPANTS: National database study of participants at least 20 years old with
      MCC, matched for age, sex, race/ethnicity, diagnosis period, tumor size, disease
      stage, surgery of the primary site, type of lymph node surgery, and geographic
      region. Exclusion criteria included survival of less than 4 months and metastatic
      disease. MAIN OUTCOMES AND MEASURES: Disease-specific survival and overall
      survival. RESULTS: Factors that were independently associated with the use of
      radiation therapy included marital status, disease stage, and type of lymph node
      surgery. Factors associated with both MCC-specific and overall survival included
      age and disease stage. Propensity scoring and matched-pair analysis resulted in
      269 matched pairs of patients and demonstrated that patients who received
      radiation therapy had improved overall survival (P = .03) but not MCC-specific
      survival (P = .26). CONCLUSIONS AND RELEVANCE: The improvement in overall
      survival among SEER patients who receive radiation therapy following surgical
      resection of MCC may be a result of selection bias or unmeasured factors and not
      radiation therapy.

PMID- 23864084
TI  - Correspondence and correlates of couples' skin cancer screening.
AB  - IMPORTANCE: Skin cancer is common among older adults. Some national organizations
      recommend total cutaneous examination (TCE) and skin self-examination (SSE) for
      skin cancer detection. Although the spousal relationship is a known influence on
      health behavior, little is known about the level of correspondence in skin
      screening among couples. OBJECTIVE: To investigate correspondence of TCE and SSE
      among older couples, demographic correlates of correspondence, and correspondence
      among barriers to skin examinations. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional online survey of cohabitating partners 50 years or older performed from
      June 1, 2010, through July 31, 2010, via the nationally representative GfK
      (Gesellschaft fur Konsumforschung or Society for Consumer Research) Internet
      panel. MAIN OUTCOMES AND MEASURES: Both TCE in the past 3 years and SSE in the
      past year. RESULTS Correspondence among partners was high. For TCE, both partners
      had completed TCE in 23.9%, and both partners had not completed TCE in 47.3%.
      With regard to SSE, both partners had completed SSE in 39.8%, and both partners
      had not completed SSE in 38.9%. Correlates of both partners not completing TCE
      include lower household income, larger household size, nonmetropolitan residence,
      living in the Midwest, and being in a same-sex relationship. Correlates of both
      members not completing SSE included larger household size and being in a same-sex
      relationship. Barriers to screening that members of couples reported were similar
      to one another. CONCLUSIONS AND RELEVANCE: Couples were mostly concordant with
      regard to engagement in skin examinations. Therefore, dyadic interventions to
      increase screening rates could be useful. Certain sociodemographic groups should
      especially be targeted.

PMID- 23864086
TI  - Notable noses.

PMID- 23864087
TI  - Barbed absorbable suture closure for large Mohs surgery defect.

PMID- 23864088
TI  - Posterolateral neck texture (insulin neck): early sign of insulin resistance.

PMID- 23864089
TI  - Attitudes and perceptions of school-aged children toward alopecia areata.

PMID- 23864090
TI  - Deep labiomental fold with pseudocomedones.

PMID- 23864091
TI  - Successful treatment of ulcerative and diabeticorum necrobiosis lipoidica with
      intravenous immunoglobulin in a patient with common variable immunodeficiency.

PMID- 23864092
TI  - Intralesional cidofovir for treating extensive genital verrucous herpes simplex
      virus infection.

PMID- 23864093
TI  - Concerns regarding results of a randomized controlled trial to promote skin self
      examination and sun protection behaviors.

PMID- 23864094
TI  - Diagnostic inaccuracy of smartphone applications for melanoma detection:
      representative lesion sets and the role for adjunctive technologies.

PMID- 23864095
TI  - Diagnostic inaccuracy of smartphone applications for melanoma detection--reply.

PMID- 23864096
TI  - Outcomes of a population-based series of early breast cancer patients with
      micrometastases and isolated tumour cells in axillary lymph nodes.
AB  - BACKGROUND: Axillary lymph node staging is traditionally important to provide
      prognostic information to guide further treatment. However, the relevance of
      isolated tumour cells (ITC) or micrometastases in axillary nodes and the need for
      adjuvant treatment remain uncertain. PATIENTS AND METHODS: Data from 18 370
      patients with pT1-2 breast cancer with pN0, pN0i+ or pN1mi were analysed. The
      primary end point was 5-year disease-free survival (locoregional recurrence,
      distant metastases or contralateral breast cancer). RESULTS: Five-year disease
      free survival was 89.9% [95% confidence interval 89.5% to 90.4%]; and did not
      differ significantly between groups. After adjusting for prognostic factors
      (including treatment), patients with ITC had a comparable risk (hazard ratio =
      1.12) as patients with node-negative disease, while patients with micrometastases
      had a 38% higher risk of recurrence. CONCLUSION(S): Patients with ITC and node
      negative breast cancer appear to have similar prognosis, and those with
      micrometastases have a 38% higher risk of tumour recurrence. However, considering
      that disease-free survival is already high, we are reluctant to advise
      chemotherapy in all patients with ITC or micrometastases. In future, genomic
      tumour characteristics might predict the propensity of dissemination from the
      primary cancer better than the status of the axillary lymph nodes.

PMID- 23864054
TI  - Combination therapy for hypertension in patients with CKD: a subanalysis of the
      Combination Therapy of Hypertension to Prevent Cardiovascular Events trial.
AB  - The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE)
      trial was a multicenter, randomized, three-arm comparative study (N=3293)
      undertaken to determine the optimal combination therapy, based on the occurrence
      of cardiovascular events in patients treated with an angiotensin II receptor
      blocker (ARB), a beta-blocker (BB) or a thiazide diuretic (TD) in addition to the
      calcium antagonist benidipine as baseline medication. This subanalysis was
      conducted to compare the efficacy of three combination therapies in a subset of
      834 patients with chronic kidney disease (CKD) (287 patients treated with
      benidpine-ARB, 283 patients treated with benidipine-BB and 264 patients treated
      with benidipine-TD). The incidence of composite cardiovascular events as the
      primary end point did not differ among these three groups. The incidence of hard
      end points and cerebrovascular events among these groups did not differ either,
      although the incidence among all patients in the COPE trial was lower in the
      benidipine-TD group than in the benidipine-BB group. The incidence of new-onset
      diabetes mellitus was higher in the benidipine-TD group than in the benidipine
      ARB group among patients with CKD. The estimated glomerular filtration rate
      (eGFR) was maintained even after 12 months of treatment in patients with a
      baseline eGFR <60 ml min(-1) per 1.73 m(2) regardless of the treatment group,
      although the eGFR decreased over time in all patients in the three groups. In
      conclusion, in patients with CKD, all of the tested combination therapies
      demonstrated comparable efficacy in terms of prevention of cardiovascular events
      as well as maintenance of eGFR.

PMID- 23864097
TI  - Primary tumor location and bevacizumab effectiveness in patients with metastatic
      colorectal cancer.
AB  - BACKGROUND: There is an unmet need for predictive markers for the antiangiogenic
      agent bevacizumab in metastatic colorectal cancer (mCRC). We aimed to assess
      whether the location of the primary tumor is associated with bevacizumab
      effectiveness when combined with capecitabine and oxaliplatin (CAPEOX) in the
      first-line treatment of patients with mCRC. PATIENTS AND METHODS: A cohort of 667
      consecutive patients with mCRC from the general community treated from 2006 to
      2011 with CAPEOX and bevacizumab as standard first-line therapy was compared with
      a cohort of 213 patients treated with CAPEOX from 2003 to 2006, before
      bevacizumab was approved. Main outcome measures were progression-free survival
      (PFS) and overall survival (OS). Differences in outcome were tested using Kaplan
      Meier curves and log-rank tests, and multivariate analyses were carried out using
      Cox Proportional Hazards models. RESULTS: Patients treated with CAPEOX and
      bevacizumab with primary tumors originating in the sigmoid colon and rectum had a
      significantly better outcome than patients with primary tumors originating from
      the cecum to the descending colon, both for PFS (median PFS 9.3 versus 7.2
      months; hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.56-0.82) and for
      OS (median OS 23.5 versus 13.0 months; HR 0.47, 95% CI 0.38-0.57). This
      difference was confirmed in multivariate analyses after adjustment for other
      potentially prognostic factors. For patients treated with CAPEOX, there was no
      association between primary tumor location and outcome, neither in unadjusted nor
      adjusted analyses. CONCLUSIONS: The addition of bevacizumab to CAPEOX in first
      line treatment of patients with mCRC may primarily benefit patients with primary
      tumors originating in the rectum and sigmoid colon. This hypothesis needs to be
      validated in data from completed randomized trials. CLINICALTRIALSGOV
      IDENTIFICATION NUMBER: NCT00212615.

PMID- 23864099
TI  - Optimizing treatment of seminoma stage IIA/B step by step.

PMID- 23864100
TI  - Semiclassical Monte-Carlo approach for modelling non-adiabatic dynamics in
      extended molecules.
AB  - Modelling of non-adiabatic dynamics in extended molecular systems and solids is a
      next frontier of atomistic electronic structure theory. The underlying numerical
      algorithms should operate only with a few quantities (that can be efficiently
      obtained from quantum chemistry), provide a controlled approximation (which can
      be systematically improved) and capture important phenomena such as branching
      (multiple products), detailed balance and evolution of electronic coherences.
      Here we propose a new algorithm based on Monte-Carlo sampling of classical
      trajectories, which satisfies the above requirements and provides a general
      framework for existing surface hopping methods for non-adiabatic dynamics
      simulations. In particular, our algorithm can be viewed as a post-processing
      technique for analysing numerical results obtained from the conventional surface
      hopping approaches. Presented numerical tests for several model problems
      demonstrate efficiency and accuracy of the new method. 

PMID- 23864101
TI  - Time course, predictors and clinical implications of stent thrombosis following
      primary angioplasty. Insights from the DESERT cooperation.
AB  - Primary percutaneous coronary intervention (pPCI) has improved survival as
      compared to thrombolysis. Concerns still remain regarding the risk of stent
      thrombosis in the setting of STEMI, especially after drug-eluting stent (DES)
      implantation. Therefore, the aim of this study was to report on the timing of
      stent thrombosis (ST) with both DES and bare metal stents (BMS) and its
      prognostic significance in patients undergoing pPCI. The Drug-Eluting Stent in
      Primary Angioplasty (DESERT) cooperation is based on a pooled database including
      individual data of randomised trials that evaluate the long-term safety and
      effectiveness of DES as compared to BMS in patients undergoing pPCI for STEMI.
      Follow-up data were collected for 3-6 years after the procedure. ST was defined
      as definite or probable, based on the ARC definition. The study population
      consists of 6,274 STEMI patients undergoing primary angioplasty with BMS or DES.
      At 1201 +/- 440 days, ST occurred in 267 patients (4.25%). Most of the events
      were acute or subacute (within 30 days) and very late (> 1 years), with different
      distribution between DES vs BMS. Patients with ST were more often diabetic (21.7%
      vs 15.1%, p=0.005), more frequently had post-procedural TIMI 0-2 flow (14.0% vs
      9.3%, p = 0.01), and were less often treated with dual antiplatelet therapy at
      one year follow-up. Diabetes (p = 0.036), post-procedural TIMI 0-2 Flow (p =
      0.013) and ischaemia time > 6 hours (p = 0.03) were independent predictors of ST.
      Post-procedural TIMI 0-2 flow (p = 0.001) and ischaemia time > 6 hours (p <
      0.001) were independent predictors of early ST, ischaemia time > 6 hours (p =
      0.05) was independent predictor of late ST, whereas diabetes (p = 0.022) and use
      of DES (p = 0.002) were independent predictors of very late ST. ST was associated
      with a significantly higher mortality (23.6% vs 6%, p < 0.001). The greatest
      impact on mortality was observed with subacute (40.4%) and late (20.9%) ST, as
      compared to acute (12.5%) and very late (9.1%) ST. ST was an independent
      predictor of mortality (HR [95%CI] = 3.73 [2.75-5.07], p < 0.001). In conclusion,
      ST occurs relatively frequently also beyond the first year for up to six years
      after pPCI in STEMI, with higher late occurrence rates among patients treated
      with first generation DES. ST after pPCI is a powerful predictor of mortality,
      especially subacute ST. 

PMID- 23864102
TI  - Sorafenib alone versus sorafenib combined with transarterial chemoembolization
      for advanced-stage hepatocellular carcinoma: results of propensity score
      analyses.
AB  - PURPOSE: To compare the time to progression (TTP) and overall survival (OS) in
      patients with advanced-stage hepatocellular carcinoma (HCC) who are undergoing
      sorafenib treatment combined with transarterial chemoembolization (TACE) versus
      sorafenib monotherapy. MATERIALS AND METHODS: The retrospective analysis of the
      data was approved by the institutional review board, and the requirement to
      obtain informed consent was waived. Of 355 patients with advanced-stage HCC
      (Barcelona Clinic Liver Cancer stage C) who were undergoing sorafenib therapy for
      at least 5 weeks between April 2007 and July 2011, 164 (46.2%) underwent repeat
      TACE (or chemolipiodolization if indicated) along with sorafenib therapy
      (combined group); the remaining 191 patients (53.8%) received sorafenib alone
      (monotherapy group). The median patient age was 53 years (range, 22-84 years).
      The median age was 53 years (range, 26-84 years) for men and 56 years (range, 22
      75 years) for women. Propensity score-based methods were used to minimize bias
      when evaluating TTP on the basis of modified Response Evaluation Criteria in
      Solid Tumors and OS. Statistical analysis was performed with the Kaplan-Meier
      method by using the log-rank test and Cox regression models. RESULTS: In the
      combined and monotherapy groups, respectively, 64.6% and 49.2% of patients had
      vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and
      47.1% had both. During follow-up (median duration, 5.5 months), the median TTP
      and OS in the combined group were longer than those in the monotherapy group
      (TTP: 2.5 months vs 2.1 months, respectively, P = .008; OS: 8.9 months vs 5.9
      months, P = .009). At univariate and subsequent multivariate analyses, additional
      TACE was an independent predictor of favorable TTP and OS (adjusted hazard ratio:
      0.74 and 0.57, respectively; P < .05 for both), consistent with the outcomes of
      inverse probability of treatment weighting. In the propensity score-matched
      cohort (96 pairs), the median TTP in the combined group was significantly longer
      than that in the monotherapy group (2.7 months vs 2.1 months, respectively; P =
      .011), but median OS was not (9.1 months vs 6.7 months, P = .21). CONCLUSION: In
      this retrospective study, TACE plus sorafenib was superior to sorafenib alone
      with respect to TTP in patients with advanced-stage HCC, although it may or may
      not improve OS. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130150/-/DC1.

PMID- 23864098
TI  - A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone
      replacement therapy users: the HOT study.
AB  - BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal
      symptoms and may decrease mortality in recently postmenopausal women, but
      increases breast cancer risk. Low-dose tamoxifen has shown retained activity in
      phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently
      postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5
      mg/day, or placebo for 5 years. The primary end point was breast cancer
      incidence. RESULTS: After 6.2 +/- 1.9 years mean follow-up, there were 24 breast
      cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46).
      Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12
      0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing
      at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse
      events did not differ between placebo and tamoxifen, including, respectively,
      coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2
      versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more
      frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did
      not significantly reduce breast cancer risk and increased climacteric symptoms in
      recently postmenopausal women. However, we noted beneficial trends in some
      subgroups which may deserve a larger study.

PMID- 23864104
TI  - Pure and part-solid pulmonary ground-glass nodules: measurement variability of
      volume and mass in nodules with a solid portion less than or equal to 5 mm.
AB  - PURPOSE: To prospectively assess and compare the measurement variability of
      volume and mass for pure and part-solid ground-glass nodules (GGNs) with solid
      portions less than or equal to 5 mm by using a commercially available volumetric
      software program. MATERIALS AND METHODS: This prospective study was approved by
      the institutional review board. Written informed consent was obtained. From
      November 2011 to June 2012, 73 patients (26 men and 47 women) with 94 GGNs (>5 mm
      and <20 mm; 72 pure and 22 part-solid GGNs) were prospectively enrolled and
      underwent two consecutive computed tomographic (CT) examinations. Both the volume
      and mass of GGNs were measured with volumetric software by two radiologists.
      Intraobserver, interobserver, and interscan variability were analyzed and
      compared by using the Bland-Altman method and coefficients of variation. The
      influence of the solid portion of GGNs and GGN size on interscan variability was
      investigated with multiple linear regression analysis and analysis of variance.
      RESULTS: Nodule segmentation was successful in 420 of 438 (95.9%) segmentations.
      As for volume measurement, interscan variability ranged from -17.3% to 18.5%,
      while intraobserver and interobserver variability ranged from -7.6% to 8.5% and
      from -11.7% to 18.1%, respectively. Interscan variability in mass measurement
      ranged from -17.7% to 18.6%, while intraobserver and interobserver variability
      ranged from -8.4% to 9.4% and from -17.5% to 11.8%, respectively. In the
      coefficient of variation comparison, there were no significant differences in
      volume and mass measurements for intraobserver, interscan, and interobserver
      variability. Measurement variability of volume and mass was not significantly
      influenced by the presence of a solid portion, solid portion size, or GGN size.
      CONCLUSION: Mass measurement of GGNs showed measurement variability from -17.7%
      to 18.6% and may be a useful method in the follow-up of GGNs with solid portions
      less than or equal to 5 mm.

PMID- 23864103
TI  - Clinical feasibility of noninvasive visualization of lymphatic flow with
      principles of spin labeling MR imaging: implications for lymphedema assessment.
AB  - PURPOSE: To extend a commonly used noninvasive arterial spin labeling magnetic
      resonance (MR) imaging method for measuring blood flow to evaluate lymphatic
      flow. MATERIALS AND METHODS: All volunteers (n = 12) provided informed consent in
      accordance with institutional review board and HIPAA regulations. Quantitative
      relaxation time (T1 and T2) measurements were made in extracted human lymphatic
      fluid at 3.0 T. Guided by these parameters, an arterial spin labeling MR imaging
      approach was adapted to measure lymphatic flow (flow-alternating inversion
      recovery lymphatic water labeling, 3 * 3 * 5 mm) in healthy subjects (n = 6; mean
      age, 30 years +/- 1 [standard deviation]; recruitment duration, 2 months).
      Lymphatic flow velocity was quantified by performing spin labeling measurements
      as a function of postlabeling delay time and by measuring time to peak signal
      intensity in axillary lymph nodes. Clinical feasibility was evaluated in patients
      with stage II lymphedema (three women; age range, 43-64 years) and in control
      subjects with unilateral cuff-induced lymphatic stenosis (one woman, two men; age
      range, 31-35 years). RESULTS: Mean T1 and T2 relaxation times of lymphatic fluid
      at 3.0 T were 3100 msec +/- 160 (range, 2930-3210 msec; median, 3200 msec) and
      610 msec +/- 12 (range, 598-618 msec; median, 610 msec), respectively. Healthy
      lymphatic flow (afferent vessel to axillary node) velocity was 0.61 cm/min +/-
      0.13 (n = 6). A reduction (P < .005) in lymphatic flow velocity in the affected
      arms of patients and the affected arms of healthy subjects with manipulated cuff
      induced flow reduction was observed. The ratio of unaffected to affected axilla
      lymphatic velocity (1.24 +/- 0.18) was significantly (P < .005) higher than the
      left-to-right ratio in healthy subjects (0.91 +/- 0.18). CONCLUSION: This work
      provides a foundation for clinical investigations whereby lymphedema etiogenesis
      and therapies may be interrogated without exogenous agents and with clinically
      available imaging equipment. Online supplemental material is available for this
      article.

PMID- 23864105
TI  - An in silico exploration of the interaction mechanism of pyrazolo[1,5
      a]pyrimidine type CDK2 inhibitors.
AB  - CDK2, which interacts with cyclin A and cyclin E, is an important member of the
      CDK family. Having been proved to be associated with many diseases for its vital
      role in cell cycle, CDK2 is a promising target of anti-cancer drugs dealing with
      cell cycle disorders. In the present work, a total of 111 pyrazolo[1,5
      a]pyrimidines (PHTPPs) as CDK2/cyclin A inhibitors were studied to conduct three
      dimensional quantitative structure-activity (3D-QSAR) analyses. The optimal
      comparative molecular similarity indices analysis (CoMSIA) model shows that Q(2)
      = 0.516, Rncv(2) = 0.912, Rpre(2) = 0.914, Rm(2) = 0.843, SEP = 0.812, SEE =
      0.347 with 10 components using steric, hydrophobic and H-bond donor field
      descriptors, indicating its effective internal and external predictive capacity.
      The contour maps further indicate that (1) bulky substituents in R1 are
      beneficial while H-bond donor groups at this position are detrimental; (2)
      hydrophobic contributions in the R2 area are favorable; (3) large and hydrophilic
      groups are well tolerated at the R3 position (a close H-bond donor moiety is
      favorable while a distal H-bond donor moiety in this area is disfavored); (4)
      bulky and hydrophobic features in the R4 region are beneficial for the biological
      activities and (5) the 7-N-aryl substitution is crucial to boost the inhibitory
      activities of the PHTPP inhibitors. Finally, docking and MD simulations
      demostrate that PHTPP derivatives are stabilized in a 'flying bat' conformation
      mainly through the H-bond interactions and hydrophobic contacts. Comparative
      studies indicate that PHTPP derivatives fit well within the ATP binding cleft in
      CDK2, with the core heterocyclic ring overlapping significantly with the adenine
      group of ATP despite a small deflection. In comparison to numerous other
      inhibitors binding to the ATP pocket, PHTPP analogues follow the binding fashion
      of purine inhibitors of this kinase. It is anticipated that the binding mechanism
      and structural features of PHTPP inhibitors studied in the present work will
      benefit the discovery of more potent CDK2 inhibitors, and the valid pyrazolo[1,5
      a]pyrimidine-7-N-yl inhibitors will soon emerge from the large number of
      screening programmes to enter in clinical studies. 

PMID- 23864106
TI  - Laboratory notebooks in the digital era: the role of ELNs in record keeping for
      chemistry and other sciences.
AB  - Egyptian evidence of scientific records dates back almost 50 centuries. In more
      recent times da Vinci and Faraday provide role models for scrupulous recording of
      ideas, observations, and conclusions. Their medium was paper, but despite the
      quality of their notebooks, we cannot turn the clock back. Our primary purpose is
      to review the influences of the digital era on scientific record keeping. We
      examine the foundations of the emerging opportunities for preserving and curating
      electronic records focussing on electronic laboratory notebooks (ELNs), with an
      emphasis on their characteristics and usability. 

PMID- 23864107
TI  - Relationship between erectile function and sexual self-confidence: a path
      analytic model in men being treated with tadalafil.
AB  - Sexual self-confidence has been shown to be associated with erectile function
      (EF) in men receiving PDE-5 inhibitor therapy; however, few studies have
      investigated the pathways (for example, sexual satisfaction, communication, time
      concerns and spontaneity) through which improvements in sexual self-confidence
      occur. This study examined this relationship using a path analysis model in men
      with ED enrolled in an open-label clinical trial of 20 mg tadalafil, administered
      on-demand over 12 weeks. International Index of Erectile Function and
      Psychological and Interpersonal Relationship Scales data were used to assess
      improvement in EF, sexual confidence and mediating variables. Controlling for
      baseline measures and covariates, the model indicated that change in sexual self
      confidence was significantly associated with changes in EF (P<0.0001), sexual
      communication conflict (P=0.01), time concerns (P<0.0001) and spontaneity
      (P<0.0001). The total effect of EF on sexual self-confidence was 0.85, with 0.08
      of this relationship indirectly mediated through time concerns and spontaneity.
      These data suggest that improved sexual confidence in men receiving treatment
      with a long-acting PDE-5 inhibitor occurs both directly via improved EF and
      indirectly via improved spontaneity and diminished time concerns. 

PMID- 23864108
TI  - Risk factors for superficial vs deep/organ-space surgical site infections:
      implications for quality improvement initiatives.
AB  - IMPORTANCE: Surgical site infections (SSIs) are the focus of numerous quality
      improvement initiatives because they are a common and costly cause of potentially
      preventable patient morbidity. Superficial and deep/organ-space SSIs differ in
      terms of anatomical location and clinical severity. OBJECTIVE: To identify risk
      factors that are uniquely predictive of superficial vs deep/organ-space SSIs
      occurring after colectomy procedures. DESIGN: Retrospective cohort study.
      SETTING: American College of Surgeons National Surgical Quality Improvement
      Program. PARTICIPANTS: Patients undergoing colectomy procedures in 2011 were
      identified by Current Procedural Terminology codes. INTERVENTION: Colectomy
      procedures. MAIN OUTCOMES AND MEASURES: We compared rates of superficial SSI and
      deep/organ-space SSI associated with perioperative variables of interest:
      demographics; preoperative clinical severity, risk factors, and comorbidities and
      variables related to the hospitalization or procedure. Hierarchical multivariable
      logistic regression models were developed to identify risk-adjusted predictors of
      each SSI type. RESULTS: Among 27 011 patients identified from 305 hospitals, 6.2%
      developed a superficial SSI and 4.7% developed a deep/organ-space SSI. Risk
      factors common to the occurrence of both SSI types were identified: open surgery
      (vs laparoscopic) and current smoker. Risk factors with differential effects on
      each SSI type included specific postoperative diagnoses, disseminated cancer, and
      irradiation therapy, which were all associated with increased odds of deep/organ
      space SSI only. The graded relationship between increasing body mass index and
      SSI occurrence appeared to be stronger for superficial SSI. CONCLUSIONS AND
      RELEVANCE: Risk factors for superficial SSI and deep/organ-space SSI vary in
      terms of magnitude and significance, suggesting that these SSI types are somewhat
      different disease processes. Groups interested in preventing SSIs might improve
      success by considering these SSI types independently for root-cause analyses and
      development of best practices and interventions.

PMID- 23864110
TI  - High energy density asymmetric supercapacitors with a nickel oxide nanoflake
      cathode and a 3D reduced graphene oxide anode.
AB  - Here we demonstrate a high energy density asymmetric supercapacitor with nickel
      oxide nanoflake arrays as the cathode and reduced graphene oxide as the anode.
      Nickel oxide nanoflake arrays were synthesized on a flexible carbon cloth
      substrate using a seed-mediated hydrothermal method. The reduced graphene oxide
      sheets were deposited on three-dimensional (3D) nickel foam by hydrothermal
      treatment of nickel foam in graphene oxide solution. The nanostructured
      electrodes provide a large effective surface area. The asymmetric supercapacitor
      device operates with a voltage of 1.7 V and achieved a remarkable areal
      capacitance of 248 mF cm(-2) (specific capacitance of 50 F g(-1)) at a
      charge/discharge current density of 1 mA cm(-2) and a maximum energy density of
      39.9 W h kg(-1) (based on the total mass of active materials of 5.0 mg).
      Furthermore, the device showed an excellent charge/discharge cycling performance
      in 1.0 M KOH electrolyte at a current density of 5 mA cm(-2), with a capacitance
      retention of 95% after 3000 cycles. 

PMID- 23864109
TI  - Interventional vs. surgical mitral valve therapy. Which technique for which
      patient?
AB  - Mitral regurgitation (MR) is the most frequent valvular heart disease in
      developed countries. Surgical repair represents the optimal treatment for severe
      degenerative MR; however, surgical correction of functional MR is controversial.
      The Euro Heart Survey showed that up to 50 % of patients with severe MR are today
      denied surgical treatment. Therefore, new transcatheter techniques have been
      developed to treat MR with less invasive approaches. Currently, the device with
      the widest clinical use is the MitraClip System. In this scenario, a
      multidisciplinary team approach is key in providing optimal individually tailored
      treatment for patients with MR. 

PMID- 23864111
TI  - Late unilateral hematoma after breast reconstruction with implants: case report
      and literature review.
AB  - Although reports of late hematoma after placement of breast implants are rare,
      there has been a noticeable increase in these reports in recent years. Various
      etiologies have been proposed, usually relating to history of trauma,
      anticoagulant use, or physical strain. In this case report, we describe a 61-year
      old patient who slowly developed a unilateral intracapsular hematoma 2 years
      after breast reconstruction with Biocell (Natrelle; Allergan, Inc, Irvine,
      California) textured implants. This case is unique because of the intraoperative
      finding of 2 capsules surrounding the implant, with the hematoma between the 2
      layers. We also discuss the possible pathophysiological mechanisms of this
      phenomenon. LEVEL OF EVIDENCE: 5.

PMID- 23864112
TI  - The role of patient activation in improving blood pressure outcomes in Black
      patients receiving home care.
AB  - Variations in patients' self-management knowledge, skills, and confidence as
      measured by the Patient Activation Measure (PAM) have been linked to variations
      in health behavior and outcomes. In a randomized trial, we tested two blood
      pressure (BP) control interventions, one grounded in activation principles. Study
      participants were Black home care patients (N = 587) with uncontrolled
      hypertension. This article examines intervention impacts on 12-month PAM score
      change, other predictors of PAM change, and associations between PAM change and
      BP outcomes. In multivariate models, the interventions did not significantly
      affect PAM change. Baseline characteristics associated with increased PAM were
      lower PAM score, higher income, higher health literacy, younger age, lower
      systolic BP, diabetes, and fewer medications. PAM increase was associated with a
      modest reduction in diastolic BP but not with improved systolic BP or BP control.
      Although studies suggest that increasing activation may lead to improved patient
      outcomes, this study did not find it to be so. 

PMID- 23864113
TI  - Rosiglitazone inhibits insulin-like growth factor-1-induced polycystic kidney
      disease cell growth and p70S6 kinase activation.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      genetic kidney disorders. Thiazolidinediones (TZDs) are anti-diabetic drugs that
      have been shown to suppress polycystic kidney diseases (PKD) development.
      However, their underlying mechanism of action remains largely unknown. Insulin
      like growth factor-1 (IGF-1) expression increases with the progression of cystic
      lesions in ADPKD and murine PKD, thus the increased expression of IGF-1 may
      contribute to the progression of cystic lesions. p70S6 kinase (p70S6K) is an
      important downstream signaling molecule of IGF-1 and is implicated in the
      regulation of cell cycle progression and cell proliferation. In the present
      study, we found that IGF-1 increased the growth of cyst-lining epithelial cells
      by 15-20% in a dose-dependent manner, while no effect on the proliferation of
      normal renal cortical tubular epithelial cells (RCTEC) was observed.
      Rosiglitazone, a TZD, was found to inhibit the IGF-1-induced growth of cyst
      lining epithelial cells when applied at a dose of 50-200 uM. However, the IGF-1
      induced growth of immortalized epithelial cells from >30 individual renal cysts
      obtained from 11 ADPKD patients (WT9-12 cells) was inhibited with a 12.5-uM dose
      of rosiglitazone. Moreover, rosiglitazone (at the same concentration) was shown
      to inhibit the IGF-1-induced activation of p70S6K. TZDs are known to exert
      antitumor properties via peroxisome proliferator-activated receptor (PPAR)gamma
      dependent and -independent mechanisms. The present study showed that PPARgamma
      small interfering RNA (siRNA) did not block the effect of rosiglitazone in
      inhibiting the IGF-1-induced phosphorylation of p70S6K. In conclusion, cyst
      lining epithelial cells were found to be more sensitive to IGF-1 compared with
      normal cells. Rosiglitazone inhibited the proliferation of cyst-lining epithelial
      cells; more specifically, it inhibited the proliferation-promoting activity of
      IGF-1 in these cells. This effect of rosiglitazone was demonstrated to be
      partially due to the inhibition of IGF-1-induced activation of p70S6K. Increased
      IGF-1 expression was identified in early-stage PKD, indicating that rosiglitazone
      is more suitable for the treatment of early-stage PKD.

PMID- 23864114
TI  - Mechanisms other than activation of the iron regulon account for the hyper
      resistance to cobalt of a Saccharomyces cerevisiae strain obtained by
      evolutionary engineering.
AB  - Cobalt is an important metal ion with magnetic properties that is widely used for
      several industrial applications. Overexposure to cobalt ions can be highly toxic
      for the organisms because they usually overwhelm the endogenous physiological
      system that maintains their homeostasis causing (geno)toxic effects. To gain
      insight into the mechanism of cobalt toxicity, we characterized at the molecular
      and genetic levels a cobalt resistant CI25E Saccharomyces cerevisiae strain
      previously isolated by an in vivo evolutionary engineering strategy, and which
      was able to grow on 5 to 10 mM CoCl2. This evolved strain showed cross-resistance
      to other metal ions including iron, manganese, nickel and zinc, but not to
      copper. Moreover, the cobalt resistant trait was semi-dominant, and linked to
      more than one gene, as indicated by the absence of 2(+):2(-) segregation of the
      cobalt resistance. Genome wide transcriptional profiling revealed a constitutive
      activation of the iron regulon that could be accounted for by a constitutive
      nuclear localization of the transcriptional activator Aft1. However, the presence
      of Aft1 in the nucleus was not a prerequisite for hyper-resistance to cobalt,
      since a mutant defective in nuclear monothiol glutaredoxin encoding GRX3 and GRX4
      that also leads to nuclear localization of Aft1 was cobalt hypersensitive. In
      addition, the loss of AFT1 only partially abolished the cobalt resistance in the
      evolved strain, and the deletion of COT1 encoding the major vacuolar transporter
      of cobalt had only a minor effect on this trait. Paradoxically to the activation
      of iron regulon, the evolved strain was hypersensitive to the iron chelator BPS,
      and this hypersensitivity was abrogated by cobalt ions. Taken together, this work
      suggested that cobalt resistance is not merely dependent upon activation of AFT1,
      but it likely implicates other mechanisms including intracellular reallocation of
      iron into important compartments whose function is dependent on this metal and
      adaptation of some cellular proteins to use Co(2+) in place of Fe(2+) for their
      catalytic activities. 

PMID- 23864123
TI  - Ionic conductivity of [Li+@C60](PF6(-)) in organic solvents and its
      electrochemical reduction to Li+@C60(.-).
AB  - The ionic conductivity of [Li(+)@C60](PF6(-)) was measured in o-dichlorobenzene,
      and found to be higher than that of TBA(+)PF6(-). Electrochemical reduction of
      [Li(+)@C60](PF6(-)) without any supporting electrolyte gave the monovalent
      radical anion Li(+)@C60(-), as confirmed by the characteristic ESR signal and NIR
      absorption band. 

PMID- 23864124
TI  - Spatial entanglement of bosons in optical lattices.
AB  - Entanglement is a fundamental resource for quantum information processing,
      occurring naturally in many-body systems at low temperatures. The presence of
      entanglement and, in particular, its scaling with the size of system partitions
      underlies the complexity of quantum many-body states. The quantitative estimation
      of entanglement in many-body systems represents a major challenge, as it requires
      either full-state tomography, scaling exponentially in the system size, or the
      assumption of unverified system characteristics such as its Hamiltonian or
      temperature. Here we adopt recently developed approaches for the determination of
      rigorous lower entanglement bounds from readily accessible measurements and apply
      them in an experiment of ultracold interacting bosons in optical lattices of
      ~10(5) sites. We then study the behaviour of spatial entanglement between the
      sites when crossing the superfluid-Mott insulator transition and when varying
      temperature. This constitutes the first rigorous experimental large-scale
      entanglement quantification in a scalable quantum simulator. 

PMID- 23864121
TI  - Evolutionary biochemistry: revealing the historical and physical causes of
      protein properties.
AB  - The repertoire of proteins and nucleic acids in the living world is determined by
      evolution; their properties are determined by the laws of physics and chemistry.
      Explanations of these two kinds of causality - the purviews of evolutionary
      biology and biochemistry, respectively - are typically pursued in isolation, but
      many fundamental questions fall squarely at the interface of fields. Here we
      articulate the paradigm of evolutionary biochemistry, which aims to dissect the
      physical mechanisms and evolutionary processes by which biological molecules
      diversified and to reveal how their physical architecture facilitates and
      constrains their evolution. We show how an integration of evolution with
      biochemistry moves us towards a more complete understanding of why biological
      molecules have the properties that they do. 

PMID- 23864122
TI  - A stochastic model for transmission, extinction and outbreak of Escherichia coli
      O157:H7 in cattle as affected by ambient temperature and cleaning practices.
AB  - Many infectious agents transmitting through a contaminated environment are able
      to persist in the environment depending on the temperature and sanitation
      determined rates of their replication and clearance, respectively. There is a
      need to elucidate the effect of these factors on the infection transmission
      dynamics in terms of infection outbreaks and extinction while accounting for the
      random nature of the process. Also, it is important to distinguish between the
      true and apparent extinction, where the former means pathogen extinction in both
      the host and the environment while the latter means extinction only in the host
      population. This study proposes a stochastic-differential equation model as an
      approximation to a Markov jump process model, using Escherichia coli O157:H7 in
      cattle as a model system. In the model, the host population infection dynamics
      are described using the standard susceptible-infected-susceptible framework, and
      the E. coli O157:H7 population in the environment is represented by an additional
      variable. The backward Kolmogorov equations that determine the probability
      distribution and the expectation of the first passage time are provided in a
      general setting. The outbreak and apparent extinction of infection are
      investigated by numerically solving the Kolmogorov equations for the probability
      density function of the associated process and the expectation of the associated
      stopping time. The results provide insight into E. coli O157:H7 transmission and
      apparent extinction, and suggest ways for controlling the spread of infection in
      a cattle herd. Specifically, this study highlights the importance of ambient
      temperature and sanitation, especially during summer. 

PMID- 23864125
TI  - Antenatal screening for Down syndrome: a quantitative demonstration of the
      improvements over the past 20 years.
AB  - OBJECTIVES: Pregnant women who receive a high screening risk result for Down,
      Edwards or Patau syndrome are offered diagnostic tests that carry a procedure
      related risk of miscarriage. This study quantifies the improvement in the
      screening tests by calculating the number of women who had such tests per
      syndrome diagnosis from 1991 to 2010. METHODS: Routinely stored data on prenatal
      chorionic villus sampling (CVS) and amniocentesis samples performed from 1991 to
      2010 from the Wessex Regional Genetics Laboratory in England were extracted from
      the laboratory database. The numbers of diagnostic tests performed per Down,
      Edwards or Patau syndrome diagnosis were calculated according to the type of
      diagnostic test, and were adjusted for maternal age and gestational age at
      diagnosis. RESULTS: A total of 32,345 CVSs and amniocenteses identified 872
      diagnoses of Down syndrome and 328 of Edwards and Patau syndrome. In 1991, there
      were 46 (95%CI: 16-111) CVSs per syndrome diagnosis compared with five (95%CI: 4
      7) in 2010. For amniocenteses, the number fell from 53 (37-78) to 15 (11-22).
      CONCLUSION: This analysis demonstrates the improvements in antenatal screening
      for Down syndrome that have been made over the past 20 years, resulting in a
      reduction in the number of women tested and thus in the number of foetal deaths
      attributable to the testing procedure.

PMID- 23864126
TI  - Temporal variability and coherence of euphotic zone bacterial communities over a
      decade in the Southern California Bight.
AB  - Time-series are critical to understanding long-term natural variability in the
      oceans. Bacterial communities in the euphotic zone were investigated for over a
      decade at the San Pedro Ocean Time-series station (SPOT) off southern California.
      Community composition was assessed by Automated Ribosomal Intergenic Spacer
      Analysis (ARISA) and coupled with measurements of oceanographic parameters for
      the surface ocean (0-5 m) and deep chlorophyll maximum (DCM, average depth ~ 30
      m). SAR11 and cyanobacterial ecotypes comprised typically more than one-third of
      the measured community; diversity within both was temporally variable, although a
      few operational taxonomic units (OTUs) were consistently more abundant.
      Persistent OTUs, mostly Alphaproteobacteria (SAR11 clade), Actinobacteria and
      Flavobacteria, tended to be abundant, in contrast to many rarer yet intermittent
      and ephemeral OTUs. Association networks revealed potential niches for key OTUs
      from SAR11, cyanobacteria, SAR86 and other common clades on the basis of robust
      correlations. Resilience was evident by the average communities drifting only
      slightly as years passed. Average Bray-Curtis similarity between any pair of
      dates was ~ 40%, with a slight decrease over the decade and obvious near-surface
      seasonality; communities 8-10 years apart were slightly more different than those
      1-4 years apart with the highest rate of change at 0-5 m between communities <4
      years apart. The surface exhibited more pronounced seasonality than the DCM.
      Inter-depth Bray-Curtis similarities repeatedly decreased as the water column
      stratified each summer. Environmental factors were better predictors of shifts in
      community composition than months or elapsed time alone; yet, the best predictor
      was community composition at the other depth (that is, 0-5 m versus DCM).

PMID- 23864127
TI  - Comparative metatranscriptomics reveals kingdom level changes in the rhizosphere
      microbiome of plants.
AB  - Plant-microbe interactions in the rhizosphere have important roles in
      biogeochemical cycling, and maintenance of plant health and productivity, yet
      remain poorly understood. Using RNA-based metatranscriptomics, the global active
      microbiomes were analysed in soil and rhizospheres of wheat, oat, pea and an oat
      mutant (sad1) deficient in production of anti-fungal avenacins. Rhizosphere
      microbiomes differed from bulk soil and between plant species. Pea (a legume) had
      a much stronger effect on the rhizosphere than wheat and oat (cereals), resulting
      in a dramatically different rhizosphere community. The relative abundance of
      eukaryotes in the oat and pea rhizospheres was more than fivefold higher than in
      the wheat rhizosphere or bulk soil. Nematodes and bacterivorous protozoa were
      enriched in all rhizospheres, whereas the pea rhizosphere was highly enriched for
      fungi. Metabolic capabilities for rhizosphere colonisation were selected,
      including cellulose degradation (cereals), H2 oxidation (pea) and methylotrophy
      (all plants). Avenacins had little effect on the prokaryotic community of oat,
      but the eukaryotic community was strongly altered in the sad1 mutant, suggesting
      that avenacins have a broader role than protecting from fungal pathogens.
      Profiling microbial communities with metatranscriptomics allows comparison of
      relative abundance, from multiple samples, across all domains of life, without
      polymerase chain reaction bias. This revealed profound differences in the
      rhizosphere microbiome, particularly at the kingdom level between plants.

PMID- 23864128
TI  - Vampires in the oceans: predatory cercozoan amoebae in marine habitats.
AB  - Vampire amoebae (vampyrellids) are predators of algae, fungi, protozoa and small
      metazoans known primarily from soils and in freshwater habitats. They are among
      the very few heterotrophic naked, filose and reticulose protists that have
      received some attention from a morphological and ecological point of view over
      the last few decades, because of the peculiar mode of feeding of known species.
      Yet, the true extent of their biodiversity remains largely unknown. Here we use a
      complementary approach of culturing and sequence database mining to address this
      issue, focusing our efforts on marine environments, where vampyrellids are very
      poorly known. We present 10 new vampyrellid isolates, 8 from marine or brackish
      sediments, and 2 from soil or freshwater sediment. Two of the former correspond
      to the genera Thalassomyxa Grell and Penardia Cash for which sequence data were
      previously unavailable. Small-subunit ribosomal DNA analysis confirms they are
      all related to previously sequenced vampyrellids. An exhaustive screening of the
      NCBI GenBank database and of 454 sequence data generated by the European BioMarKs
      consortium revealed hundreds of distinct environmental vampyrellid sequences. We
      show that vampyrellids are much more diverse than previously thought, especially
      in marine habitats. Our new isolates, which cover almost the full phylogenetic
      range of vampyrellid sequences revealed in this study, offer a rare opportunity
      to integrate data from environmental DNA surveys with phenotypic information.
      However, the very large genetic diversity we highlight within vampyrellids
      (especially in marine sediments and soils) contrasts with the paradoxically low
      morphological distinctiveness we observed across our isolates. 

PMID- 23864129
TI  - Angiogenesis inhibition for glioblastoma at the edge: beyond AVAGlio and RTOG
      0825.

PMID- 23864130
TI  - The impact of eplerenone at different levels of risk in patients with systolic
      heart failure and mild symptoms: insight from a novel risk score for prognosis
      derived from the EMPHASIS-HF trial.
AB  - AIMS: Our objective was to create a simple prognostic risk score for patients
      with systolic heart failure and mild symptoms. We then assessed the efficacy of
      eplerenone across different categories of risk. METHODS AND RESULTS: The
      Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure
      trial (EMPHASIS-HF) was an international randomized trial, comparing eplerenone
      with placebo in 2737 patients with systolic heart failure and mild symptoms. The
      primary outcome was a composite of cardiovascular death or hospitalization for
      heart failure, over a median 2.1 years follow-up. Using multivariable Cox
      modelling age, sex, systolic blood pressure, estimated glomerular filtration
      rate, diabetes, BMI, haemoglobin, prior heart failure (HF) hospitalization, prior
      myocardial infarction/coronary artery bypass surgery (CABG), and heart rate were
      identified as strong independent risk factors. Estimates from the model were
      converted into a simple integer risk score which was categorized into three
      groups of low-, medium-, and high risk. In placebo patients, the rates (per 100
      patient-years) for the primary outcome were 7.6, 19.0, and 39.4 in the low-,
      medium-, and high-risk groups, respectively. On eplerenone, these rates were
      reduced to 5.6, 12.2, and 24.2, respectively. Eplerenone was beneficial across
      all risk categories and the hazard ratios were similar. The absolute treatment
      benefit was greatest among those at highest risk. Similar patterns emerged for
      all-cause mortality and for all HF hospitalizations. CONCLUSION: This easy-to-use
      integer risk score should be of value in quantifying individual patient risk in
      patients with systolic HF and mild symptoms. The relative benefits of eplerenone
      appeared consistent across the whole spectrum of risk, including those at lower
      risk.

PMID- 23864131
TI  - More answers to the still unresolved question of nitrate tolerance.
AB  - Organic nitrates are traditionally felt to be a safe adjuvant in the chronic
      therapy of patients with coronary artery disease. Despite their long use,
      progress in the understanding of the pharmacology and mechanism of action of
      these drugs has been achieved only in the last two decades, with the
      identification of the role of oxidative stress in the pathophysiology of nitrate
      tolerance, with, the discovery of the ancillary effects of nitrates, and with the
      demonstration that nitrate therapy has important chronic side effects that might
      modify patients' prognosis. These advances are however mostly confined to the
      molecular level or to studies in healthy volunteers, and the true impact of
      organic nitrates on clinical outcome remains unknown. Complicating this issue,
      evidence supports the existence of important differences among the different
      drugs belonging to the group, and there are reasons to believe that the nitrates
      should not be treated as a homogeneous class. As well, the understanding of the
      effects of alternative nitric oxide (NO) donors is currently being developed, and
      future studies will need to test whether the properties of these new medications
      may compensate and prevent the abnormalities imposed by chronic nitrate therapy.
      Intermittent therapy with nitroglycerin and isosorbide mononitrate is now
      established in clinical practice, but they should neither be considered a
      definitive solution to the problem of nitrate tolerance. Both these strategies
      are not deprived of complications, and should currently be seen as a compromise
      rather than a way fully to exploit the benefits of NO donor therapy. 

PMID- 23864132
TI  - The heart and the gut.
AB  - The heart and the gut seem to be two organs that do not have much in common.
      However, there is an obvious and clinically relevant impact of gut functions on
      the absorption of drugs and oral therapies on the one hand. On the other hand,
      the gut determines the quantity of nutrient uptake and plays a central role in
      metabolic diseases. Patients with inflammatory bowel diseases appear to have a
      higher risk for coronary heart disease despite a lower prevalence of 'classical'
      risk factors, indicating additional links between the gut and the heart. However,
      they certainly have a 'leaky' intestinal barrier associated with increased
      permeability for bacterial wall products. An impaired intestinal barrier function
      will be followed by bacterial translocation and presence of bacterial products in
      the circulation, which can contribute to atherosclerosis and chronic heart
      failure (CHF) as recent data indicate. Impaired cardiac function in CHF vice
      versa impacts intestinal microcirculation leading to a barrier defect of the
      intestinal mucosa and increased bacterial translocation. These pathways and the
      most recent insights into the impact of the gut on acute and chronic heart
      disease will be discussed in this review.

PMID- 23864133
TI  - Recent trends in morbidity and in-hospital outcomes of in-patients with
      peripheral arterial disease: a nationwide population-based analysis.
AB  - AIMS: The prevalence of peripheral arterial disease (PAD) and especially of
      critical limb ischaemia (CLI) is announced to rise dramatically worldwide, with a
      considerable impact on the health care and socio-economic systems. We aimed to
      characterize the recent trends in morbidity and in-hospital outcome of PAD among
      all hospitalized patients in the entire German population between 2005 and 2009.
      METHODS AND RESULTS: Nationwide data of all hospitalizations in Germany in 2005,
      2007, and 2009 were analysed regarding the prevalence of PAD, comorbidities,
      endovascular (EVR) and surgical revascularizations (SR), major and minor
      amputations, in-hospital mortality, and associated costs. From 2005 to 2009,
      total PAD cases increased by 20.7% (from 400 928 to 483 961), with an increase of
      CLI subset from 40.6 to 43.5%. Total EVR increased by 46%, while thromb
      embolectomy, endarterectomy, and patch plastic increased by 67, 42, and 21%,
      respectively. Peripheral bypasses decreased by 2%. Major amputation decreased
      from 4.6 to 3.5%, while minor amputation slightly increased from 4.98 to 5.11%.
      The crude overall in-hospital mortality remained unchanged in claudicants (2.2%),
      while it decreased from 9.8 to 8.4% in CLI patients. However, mortality rate
      according to the Poisson model (n/1000 hospital residence days) increased
      significantly in claudicants (P < 0.001). Total reimbursement costs for PAD in
      patient care increased by 21% with an average per case costs in 2009 of ?4506 in
      a claudicant and ?6791 in a CLI patient. CONCLUSION: This population-based
      analysis documents the significant rise of PAD, particularly of the CLI subset,
      and highlights the malign prognosis associated with PAD as indicated by high
      amputation and in-hospital mortality rates.

PMID- 23864134
TI  - A new look at atrial fibrillation: lessons learned from drugs, pacing, and
      ablation therapies.
AB  - Atrial fibrillation (AF) is the most common arrhythmia and among the leading
      causes of stroke and heart failure in Western populations. Despite the increasing
      size of clinical trials assessing the efficacy and safety of AF therapies,
      achieved outcomes have not always matched expectations. Considering that AF is a
      symptom of many possible underlying diseases, clinical research for this
      arrhythmia should take into account their respective pathophysiology.
      Accordingly, the definition of the study populations to be included should rely
      on the established as well as on the new classifications of AF and take advantage
      from a differentiated look at the AF-electrocardiogram and from increasingly
      large spectrum of biomarkers. Such an integrated approach could bring researchers
      and treating physicians one step closer to the ultimate vision of personalized
      therapy, which, in this case, means an AF therapy based on refined diagnostic
      elements in accordance with scientific evidence gathered from clinical trials. By
      applying clear-cut patient inclusion criteria, future studies will be of smaller
      size and thus of lower cost. In addition, the findings from such studies will be
      of greater predictive value at the individual patient level, allowing for
      pinpointed therapeutic decisions in daily practice. 

PMID- 23864136
TI  - A plea for biobanking of all equivocal melanocytic proliferations.

PMID- 23864135
TI  - Multivariate miRNA signatures as biomarkers for non-ischaemic systolic heart
      failure.
AB  - AIMS: Non-ischaemic heart failure is one of the today's most prevalent
      cardiovascular disorders. Since modern pharmacotherapy has proved to be very
      effective in delaying disease progression and preventing death, imaging
      modalities and molecular biomarkers play an important role in early
      identification and clinical management as well as risk assessment of patients.
      The present study evaluated for the first time whole peripheral blood miRNAs as
      novel biomarker candidates for non-ischaemic heart failure with reduced ejection
      fraction (HF-REF). METHODS AND RESULTS: We assessed genome-wide miRNA expression
      profiles in 53 HF-REF patients and 39 controls. We could identify and validate
      several miRNAs that show altered expression levels in non-ischaemic HF-REF,
      discriminating cases from controls both as single markers or when combined in a
      multivariate signature. In addition, we demonstrate that the miRNAs of this
      signature significantly correlate with disease severity as indicated by left
      ventricular ejection fraction. CONCLUSION: Our data further denote that miRNAs
      are potential biomarkers for systolic heart failure. Since their detection levels
      in whole blood are also related to the degree of left ventricular dysfunction,
      they may serve as objective molecular tools to assess disease severity and
      prognosis.

PMID- 23864137
TI  - The optoelectronic behaviour of carbon nanoparticles: evidence of the importance
      of the outer carbon shell.
AB  - The particular properties of carbon nanoparticles (CNPs) have generated great
      interest in biomedicine, bioanalysis and optoelectronics. However, an association
      between the CNPs' physicochemical properties with their molecular and
      morphological characteristics is, even today, a topic of discussion. In this
      work, we use a simple method of synthesis with the ultimate aim of elucidating
      the structural nature of the obtained CNPs and its relationship with their well
      known fluorescent properties. The sample is studied by high-resolution
      transmission electron microscopy (HRTEM), electron energy-loss spectroscopy
      (EELS), nuclear magnetic resonance (NMR), UV-visible and IR spectroscopy,
      electrochemistry and electrogenerated chemiluminescence (ECL). The results showed
      that the nanoparticles are constituted by a graphitic core surrounded by an
      amorphous layer, which seems to be significant in the determination of the
      optical and electronic properties observed in the system under study. 

PMID- 23864138
TI  - 19F NMR: a valuable tool for studying biological events.
AB  - With the spectacular advancement of NMR techniques and the flourishing of
      fluorine chemistry allowing the synthesis of various fluorinated molecules, (19)F
      NMR represents a compelling option for studying myriad biological events ranging
      from the structure and function of biomolecules, enzymatic mechanisms, and
      metabolic pathways, through to drug screening and discovery as well as medical
      imaging. In this tutorial review, we aim to provide readers with a brief overview
      of the recent applications of (19)F NMR in various areas relating to biological
      and biomedical research, together with a brief introduction of specific hardware
      improvements permitting the practical implementation of (19)F NMR. 

PMID- 23864139
TI  - Long-term benefits of radon spa therapy in rheumatic diseases: results of the
      randomised, multi-centre IMuRa trial.
AB  - In chronic rheumatic diseases, recent treatment regimens comprise multimodal
      concepts including pharmacologic, physical/exercise, occupational and
      psychological therapies. Rehabilitation programmes are used for long-term
      management of disease. Spa therapy is often integrated in various middle and
      south European and Asian countries. Here, we investigated radon spa therapy as
      applied in health resorts compared to a control intervention in rheumatic out
      patients. Randomised, blinded trial enroling 681 patients [mean age 58.3
      (standard deviation 11.1); female 59.7%] in 7 health resorts in Germany and
      Austria with chronic back pain (n 1 = 437), osteoarthritis (OA) (n 2 = 230),
      rheumatoid arthritis (n 3 = 98), and/or ankylosing spondylitis (n 4 = 39);
      multiple nominations in 146 cases). Outcomes were pain (primary), quality of
      life, functional capacity, and medication measured before start, after end of
      treatment, and 3 times thereafter in 3 monthly intervals. Adverse events were
      documented. To analyse between-group differences, repeated-measures analysis of
      covariance was performed in metric endpoints and Fisher's exact test in rates.
      Two-sided significance level of 5% was chosen. Until end of follow-up,
      superiority of radon therapy was found regarding pain relief (p = 0.032) and
      analgesic drug consumption (p = 0.007), but not regarding quality of life.
      Functional capacity was assessed specific to the underlying indication.
      Significant benefits were found in radon-treated OA patients until 6-month follow
      up (p = 0.05), but not until end of study (p = 0.096). Neither the back pain sub
      population nor the two smaller patient populations with inflammatory indications
      benefited significantly in functional capacity. Results suggest beneficial
      analgesic effects of radon spa therapy in rheumatic diseases until 9 months post
      intervention.

PMID- 23864140
TI  - Wnt-related genes and large-joint osteoarthritis: association study and
      replication.
AB  - Osteoarthritis (OA) has a strong genetic component, and experimental evidence
      suggests the involvement of the Wnt pathway in its pathogenesis. Hence, we
      explored the association of common single nucleotide polymorphisms (SNPs) related
      to the Wnt pathway with hip and knee OA. Seventy-eight SNPs were analyzed in 606
      patients undergoing joint replacement and in 680 control subjects. SNPs were
      located in WNT1, WNT10A, WNT16, DVL2, FZD5, BCL9, SFRP1, TCF7L1 and SFRP4 genes.
      SNPs significantly associated with OA were genotyped in an independent group of
      369 patients and 407 controls. One SNP in WNT10A, rs3806557, was associated with
      hip OA in men (OR 0.65, 95% CI 0.46-0.93; p = 0.017), but the association was not
      confirmed in the replication phase. The TCF7L1 polymorphism rs11547160 was also
      associated with hip OA in the discovery set, but not in the replication set.
      Similarly, the SFRP4 SNP rs1052981 was associated with knee OA in women with OR
      of 2.73 (95% CI 1.29-5.8; p = 0.006), but the association was not replicated. The
      BCL9 polymorphism rs2353525 was associated with knee OA in women, both in the
      unadjusted and in the age- and BMI-adjusted analysis (OR 2.01; 95% CI 1.34-2.98;
      p = 0.0006). A similar, but not statistically significant, trend was observed in
      the replication phase. In the combined analysis, OR was 3.13 (1.34-7.28; p =
      0.009). These data suggest that some SNPs of genes related to the Wnt pathway
      and, specifically BCL9, influence the genetic predisposition to osteoarthritis of
      the large joints in a sex- and joint-specific way.

PMID- 23864141
TI  - Clarithromycin in rheumatoid arthritis: the addition to methotrexate and low-dose
      methylprednisolone induces a significant additive value--a 24-month single-blind
      pilot study.
AB  - To compare the efficacy of the addition of clarithromycin (CM) to methotrexate
      (MTX) and methylprednisolone (MP) in active rheumatoid arthritis (RA). 32
      patients with RA consecutively randomized. CONTROL GROUP: sixteen patients
      treated for 24 months with MTX 10-15 mg i.m. weekly and MP 4-6 mg daily. CM
      group: sixteen patients treated with MTX 10-15 mg i.m. weekly and MP 4-6 mg daily
      for 24 months; CM therapy added in the first month (500 mg twice a day for the
      first 15 days followed by 500 mg a day for the remaining 15 days). Evaluation of
      the improvement following ACR criteria was performed at months 1 (primary
      endpoint), 3 and 6. Patients were furthermore observed after 12, 18 and 24 months
      from the study beginning. At month 1, following ACR70 improvement criteria, we
      found a significant additive value in CM group (10/16 = 63% vs 4/16 = 25%, p =
      0.033--chi-square test). After discontinuation of CM, the difference between
      groups was anymore evident (month 3: CM group 10/16 = 63% vs control group 9/16 =
      56%). At month 24, 7/16 (44%) in control group and 12/16 (75%) in CM group
      completed the follow-up. The addition of CM to MTX and MP can induce the
      remission ACR 70 in the majority of RA patients within 4 weeks, while MTX and MP
      alone need about 3 months to achieve the same result.

PMID- 23864142
TI  - Levels of dipeptidyl peptidase IV/CD26 substrates neuropeptide Y and vasoactive
      intestinal peptide in rheumatoid arthritis patients.
AB  - Neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) have their
      biological half-lives controlled by dipeptidyl peptidase IV (DPP IV/CD26).
      Several lines of evidence suggest the involvement of NPY in the regulation of
      rheumatoid arthritis (RA), and VIP has already been identified as a potent anti
      inflammatory factor that reduces joint inflammation. The role of DPP IV/CD26 in
      the pathogenesis of RA has been indicated, but its mediator actions involving NPY
      and VIP have not been well investigated, so the aim of this study was to find an
      association between NPY, VIP, and DPP IV/CD26 in RA patients. Assessment of NPY,
      VIP, DPP IV/CD26 as well as some other inflammatory markers was carried out in 20
      RA patients being treated with different types of drugs. Control group consisted
      of 18 osteoarthritis patients. Synovial fluid and serum content of investigated
      molecules was determined by ELISA and DPP IV/CD26 activity was measured
      spectrophotometrically. Immunodetection showed elevated levels of NPY and VIP in
      RA patients, with a significant increase in synovial fluid, while concentration
      and activity of DPP IV/CD26 were significantly decreased in both synovial fluid
      and serum. Positive correlations between serum DPP IV/CD26 concentration and
      activity (R = 0.6961), as well as between serum and synovial fluid concentration
      of VIP (R = 0.7029) were found. In RA group, NPY, VIP, and DPP IV/CD26
      concentrations were not affected by the administration of drugs. The results of
      this study indicate a connection between elevated concentration of NPY and VIP
      and decreased DPP IV/CD26 activity and concentration, suggesting a potential role
      of these molecules in the immunomodulation of RA.

PMID- 23864143
TI  - A polymorphism in ERAP1 is associated with susceptibility to ankylosing
      spondylitis in a Turkish population.
AB  - We assessed the role played by the ERAP1 gene in Turkish patients with ankylosing
      spondylitis (AS) in terms of disease susceptibility, clinical manifestations, and
      disease severity. We included 150 consecutive AS patients who met the modified
      New York classification criteria and 150 healthy controls. We documented the
      presence of 10 ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 in these
      patients. ERAP1 SNPs were genotyped using competitive allele-specific polymerase
      chain reaction. Differences between genotype and allele frequencies were compared
      using the Pearson's Chi-square test. The associations between ERAP1 SNPs, on the
      one hand, and with disease severity and clinical findings, on the other, were
      determined. One SNP, rs26653, was significantly associated with AS susceptibility
      (OR 1.609, 95% CI 1.163-2.226; p = 0.004). The population-attributable risk of
      possession of the rs26653 SNP allele was 23.4%. No relationship was noted between
      HLA-B27 positivity and the distribution of rs26653 genotype frequency. No
      associations were seen between disease severity measures and clinical
      manifestations of AS. In summary, an ERAP1 polymorphism was associated with AS in
      a Turkish population. The contributions of HLA-B27 and the rs26653 SNP to AS
      pathogenesis appear to be independent.

PMID- 23864144
TI  - The effect of TGF-beta1 polymorphism on systemic sclerosis: a systematic review
      and pooled analysis of available literature.
AB  - Transforming growth factor-beta1 (TGF-beta1) plays an important role in the
      pathogenesis of systemic sclerosis (SSc). To investigate whether TGF-beta1 gene
      promoter polymorphisms were associated with the susceptibility of SSc, we
      performed a meta-analysis based on all available studies through PubMed, Elsevier
      Science Direct, Embase, and Chinese Biomedical, China National Knowledge
      Infrastructure and Google Scholar with the last report up to March 15, 2013.
      Crude odds ratios with 95% confidence intervals were used to estimate the
      strength of the association. A fixed or random effects model was adopted
      according to heterogeneity test. Heterogeneity among studies was evaluated using
      I (2) . Meta-regression was used to explore potential sources of between-study
      heterogeneity. Publication bias was estimated using Begg's and Egger's test.
      Totally, seven papers with 663 SSc patients and 908 healthy controls were
      subjected to the final analysis. These studies encompass seven for TGF-beta1
      codon 10, three for codon 25 and three for -509C/T. We failed to detect any
      association of these promoter polymorphism with SSc susceptibility. For TGF-beta1
      codon 10 polymorphism, subgroup analyses by race, genotype testing method and
      classification of SSc were further performed. Similarly, no association was
      observed. Significant heterogeneity was detected among the studies in all genetic
      models of TGF-beta1 codon 10 polymorphism. Publication bias was absent. Taken
      together, our meta-analysis did not provided an evidence of confirming
      association between TGF-beta1 (codon 10, codon 25, -509C/T) gene polymorphism and
      SSc. Nevertheless, due to smaller sample sizes, larger sample studies including
      different ethnic groups should be considered in future to confirm our results.

PMID- 23864145
TI  - Three-dimensional spine model reconstruction using one-class SVM regularization.
AB  - Statistical shape models have become essential for medical image registration or
      segmentation and are used in many biomedical applications. These models are often
      based on Gaussian distributions learned from a training set. We propose in this
      paper a shape model which does not rely on the estimation of a Gaussian
      distribution, but on similarities computed with a kernel function. Our model
      takes advantage of the one-class support vector machine (OCSVM) to do so. In this
      context, we propose in this paper a method for reconstructing the spine of
      scoliotic patients using OCSVM regularization. Current state-of-the-art methods
      use conventional statistical shape models, and the reconstruction is commonly
      processed by minimizing a Mahalanobis distance. Nevertheless, when a shape
      differs significantly from the statistical model, the associated Mahalanobis
      distance often overstates the need for statistical regularization. We show that
      OCSVM regularization is more robust and is less sensitive to weak landmarks
      definition and is hardly influenced by the presence of outliers in the training
      data. The proposed OCSVM model applied to 3-D spine reconstruction was evaluated
      on real patient data, and results showed that our approach allows precise
      reconstruction. 

PMID- 23864146
TI  - Integrating Retraction Modeling Into an Atlas-Based Framework for Brain Shift
      Prediction.
AB  - In recent work, an atlas-based statistical model for brain shift prediction,
      which accounts for uncertainty in the intraoperative environment, has been
      proposed. Previous work reported in the literature using this technique did not
      account for local deformation caused by surgical retraction. It is challenging to
      precisely localize the retractor location prior to surgery and the retractor is
      often moved in the course of the procedure. This paper proposes a technique that
      involves computing the retractor-induced brain deformation in the operating room
      through an active model solve and linearly superposing the solution with the
      precomputed deformation atlas. As a result, the new method takes advantage of the
      atlas-based framework's accounting for uncertainties while also incorporating the
      effects of retraction with minimal intraoperative computing. This new approach
      was tested using simulation and phantom experiments. The results showed an
      improvement in average shift correction from 50% (ranging from 14 to 81%) for
      gravity atlas alone to 80% using the active solve retraction component (ranging
      from 73 to 85%). This paper presents a novel yet simple way to integrate
      retraction into the atlas-based brain shift computation framework. 

PMID- 23864147
TI  - Noninvasive and Nonocclusive Blood Pressure Estimation Via a Chest Sensor.
AB  - The clinical demand for a device to monitor blood pressure (BP) in ambulatory
      scenarios with minimal use of inflation cuffs is increasing. Based on the so
      called pulse wave velocity (PWV) principle, this paper introduces and evaluates a
      novel concept of BP monitor that can be fully integrated within a chest sensor.
      After a preliminary calibration, the sensor provides nonocclusive beat-by-beat
      estimations of mean arterial pressure (MAP) by measuring the pulse transit time
      (PTT) of arterial pressure pulses travelling from the ascending aorta toward the
      subcutaneous vasculature of the chest. In a cohort of 15 healthy male subjects, a
      total of 462 simultaneous readings consisting of reference MAP and chest PTT were
      acquired. Each subject was recorded at three different days: D, D+3, and D+14.
      Overall, the implemented protocol induced MAP values to range from 80 +/- 6 mmHg
      in baseline, to 107 +/- 9 mmHg during isometric handgrip maneuvers. Agreement
      between reference and chest-sensor MAP values was tested by using intraclass
      correlation coefficient (ICC = 0.78) and Bland-Altman analysis (mean error = 0.7
      mmHg, standard deviation = 5.1 mmHg). The cumulative percentage of MAP values
      provided by the chest sensor falling within a range of +/-5 mmHg compared to
      reference MAP readings was of 70%, within +/-10 mmHg was of 91%, and within +/-15
      mmHg was of 98%. These results point at the fact that the chest sensor complies
      with the British Hypertension Society requirements of Grade A BP monitors, when
      applied to MAP readings. Grade A performance was maintained even two weeks after
      having performed the initial subject-dependent calibration. In conclusion, this
      paper introduces a sensor and a calibration strategy to perform MAP measurements
      at the chest. The encouraging performance of the presented technique paves the
      way toward an ambulatory compliant, continuous, and nonocclusive BP monitoring
      system. 

PMID- 23864148
TI  - 3D Vascular Decomposition and Classification for Computer-Aided Detection.
AB  - In this study, we propose a weighted approximate convex decomposition (WACD) and
      classification methodology for computer-aided detection (CADe) and analysis. We
      start by addressing the problem of vascular decomposition as a cluster
      optimization problem and introduce a methodology for compact geometric
      decomposition. The classification of decomposed vessel sections is performed
      using the most relevant eigenvalues obtained through feature selection. The
      method was validated using presegmented sections of vasculature archived for 98
      aneurysms in 112 patients. We test first for vascular decomposition and next for
      classification. The proposed method produced promising results with an estimated
      81.5% of the vessel sections correctly decomposed. Recursive feature elimination
      was performed to find the most compact and informative set of features. We showed
      that the selected subset of eigenvalues produces minimum error and improved
      classifier precision. The method was also validated on a longitudinal study of
      four cases having internal cerebral aneurysms. Volumetric and surface area
      comparisons were made between expert-segmented sections and WACD classified
      sections containing aneurysms. Results suggest that the approach is able to
      classify and detect changes in aneurysm volumes and surface areas close to that
      segmented by an expert. 

PMID- 23864149
TI  - Stochastic Virtual Population of Subjects With Type 1 Diabetes for the Assessment
      of Closed-Loop Glucose Controllers.
AB  - Closed-loop glucose control is an emerging treatment approach to manage type 1
      diabetes. Closed-loop systems consist of a continuous glucose monitor, an insulin
      infusion pump, and a dosing algorithm that directs insulin delivery based on
      sensor levels. Testing of dosing algorithms in computer simulations may replace
      animal testing, accelerates development, and saves resources. We propose here a
      novel approach to generate a virtual population, to be used in metabolic
      simulators, from routine experimental data through the process that we term
      "stochastic e-cloning." We build on a nonlinear physiologically motivated time
      varying model of glucose regulation. We adopt the Bayesian approach to estimate
      model parameters and to obtain the joint posterior probability distribution of
      time-invariant and time-varying parameters with the use of the Markov chain Monte
      Carlo methodology. The estimation process combines prior knowledge and
      experimental data to generate a sample from the posterior distribution, which can
      be subsequently used to conduct in silico experiments reflecting population and
      individual variability, and associated uncertainty as closely as possible. The
      approach is exemplified using data collected in 12 young subjects with type 1
      diabetes. We demonstrate unbiased fit to the data, physiological plausibility of
      parameter estimates, and results of in silico testing using a stochastic virtual
      subject. 

PMID- 23864150
TI  - Infrared Neural Stimulation: Influence of Stimulation Site Spacing and Repetition
      Rates on Heating.
AB  - A model to simulate heating as a result of pulse repetitions during infrared
      neural stimulation (INS), with both single- and multiple-emitters is presented.
      This model allows the temperature increases from pulse trains rather than single
      pulses to be considered. The model predicts that using a stimulation rate of 250
      Hz with typical laser parameters at a single stimulation site results in a
      temperature increase of 2.3 degrees C. When multiple stimulation sites are used
      in analogy to cochlear implants, the temperature increases further depending upon
      the spacing between emitters. However, when the light is more localized at
      multiple stimulation sites the temperature increase is reduced. 

PMID- 23864151
TI  - Optimal Intervention in Markovian Gene Regulatory Networks With Random-Length
      Therapeutic Response to Antitumor Drug.
AB  - The most effective cancer treatments are the ones that prolong patients' lives
      while offering a reasonable quality of life during and after treatment. The
      treatments must also carry out their actions rapidly and with high efficiency
      such that a very large percentage of tumor cells die or shift into a state where
      they stop proliferating. Due to biological and microenvironmental variabilities
      within tumor cells, the action period of an administered drug can vary among a
      population of patients. In this paper, based on a recently proposed model for
      tumor growth inhibition, we first probabilistically characterize the variability
      of the length of drug action. Then, we present a methodology to devise optimal
      intervention strategies for any Markovian genetic regulatory network governing
      the tumor when the antitumor drug has a random-length duration of action. 

PMID- 23864152
TI  - CREPE: mathematical model for crosstalking of endothelial cells and hepatocyte
      metabolism.
AB  - The liver shows a close coexistence between endothelial cells and hepatocytes
      (HepG2). Endothelial cells' main purpose is to protect (HepG2) from blood vessel
      shear stress, acting as a barrier, but experimental evidence suggests that they
      could also play a role in regulating (HepG2) glucose metabolism. A well-known
      singular effect in hepatocyte-endothelial co-cultures is the reduction of glucose
      consumption respect to (HepG2) in single culture. (HepG2) were shown to reduce
      their glucose consumption supporting energy needs of endothelial cells. Monti
      have studied the effects of endothelin-1 (Et-1) on Glucokinase activity in adult
      rat (HepG2). They observed a reduction in hepatocytes Glucokinase catalytic rate,
      which is dependent on Et-1 concentration. We developed crosstalking of
      endothelial cells and hepatocyte metabolism (CREPE) that is a mathematical model
      of the endothelin-1 mediated crosstalk between HepG2 and endothelial cells (human
      umbilical vein endothelial cells) in a traditional static co-culture system.
      CREPE was validated against experimental data, showing good agreement with them.
      CREPE can be a starting point to develop predictive tools on complex and highly
      interconnected environments. 

PMID- 23864153
TI  - Association between MTHFR C677T, MTHFR A1298C and MS A2756G polymorphisms and
      risk of cervical intraepithelial neoplasia II/III and cervical cancer: a meta
      analysis.
AB  - Numerous case-control studies on the association between polymorphisms of key
      genes involved in methionine remethylation [methylenetetrahydrofolate reductase
      (MTHFR) and methionine synthase (MS)] and the susceptibility of cervical
      intraepithelial neoplasia (CIN) and cervical cancer have provided inconclusive
      results. The aim of the present meta-analysis was to determine the effects of two
      MTHFR (C677T and A1298C) and one MS gene polymorphism (A2756G) on the risk of CIN
      II/III or cervical cancer. Relevant data were retrieved following a systematic
      search in PubMed, Web of Science, MEDLINE and Wanfang Data up to November 2012.
      Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated from
      eligible studies by meta-analysis with subgroup analyses stratified by ethnicity.
      A total of 13 studies with 1,936 cases and 2,858 controls were included in the
      present meta-analysis. An increased risk of cervical cancer was found in Asian
      women with the MTHFR 677T allele (TT vs. CC: OR=1.41, 95% CI=1.07-1.86, P=0.01;
      TT vs. CC+CT: OR=1.38, 95% CI=1.08-1.75, P=0.008), while a decreased risk was
      observed in Caucasian women (TT vs. CC: OR=0.65, 95% CI=0.45-0.93, P=0.02; TT+CT
      vs. CC: OR=0.7, 95% CI=0.58-0.86, P=0.0005). No effects of MTHFR C677T
      polymorphism on CIN II/III risk and MTHFR A1298C or MS A2756G polymorphisms on
      cervical cancer risk were detected. The sensitivity analysis suggested stability
      of this meta-analysis and no publication bias was detected. The MTHFR 677T allele
      may enhance the risk of cervical cancer in the Asian female population and play a
      protective role in Caucasian females. However, limited association is suggested
      between MTHFR A1298C and MS A2756G polymorphisms with cervical tumorigenesis.

PMID- 23864154
TI  - Everything you always wanted to know about cone beam computed tomography: 3D
      Roentgen.ch.

PMID- 23864155
TI  - Platelets and matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) and their inhibitors essentially contribute to a
      variety of pathophysiologies by modulating cell migration, tissue degradation and
      inflammation. Platelet-associated MMP activity appears to play a major role in
      these processes. First, platelets can concentrate leukocyte-derived MMP activity
      to sites of vascular injury by leukocyte recruitment. Second, platelets stimulate
      MMP production in e.g. leukocytes, endothelial cells, or tumour cells by direct
      receptor interaction or/and by paracrine pathways. Third, platelets synthesise
      and secrete a variety of MMPs including MMP-1, MMP-2, MMP-3, and MMP-14 (MT1
      MMP), and potentially MMP-9 as well as the tissue inhibitors of metalloproteinase
      (TIMPs). This review focuses on platelet-derived and platelet-induced MMPs and
      their inhibitors. 

PMID- 23864156
TI  - Meeting report of the 4th Heidelberg Myeloma Workshop: current status and
      developments in diagnosis and therapy of multiple myeloma.

PMID- 23864157
TI  - Median neuropathy in malunited fractures of the distal radius.
AB  - PURPOSE: Irritation of the median nerve is a well-characterized complication
      after acute fractures of the distal radius, but there is limited literature on
      median neuropathy in malunited fractures. The aims of our prospective study were
      to estimate the prevalence of the median neuropathy, explore the relationship
      between radiographic findings and the condition, and investigate whether
      corrective osteotomy without carpal tunnel release was a sufficient treatment.
      METHODS: Thirty consecutive patients, who were referred to us for treatment of
      symptomatic distal radial malunion, underwent nerve conduction studies of both
      wrists by one board-certified neurologist under standardized conditions. Test
      results were correlated with conventional radiographic parameters (radial tilt,
      radial inclination, palmar shift, ulnar variance, radiolunate and capitolunate
      angle) and computer tomography (CT) based measurements of the cross-sectional
      area of the carpal tunnel. After corrective osteotomy without carpal tunnel
      release, 10 of 13 patients with unilateral preoperative median neuropathy agreed
      to an electrodiagnostic re-examination by the same neurologist. RESULTS: Nineteen
      patients demonstrated abnormal test results, but only seven patients complained
      about paresthesias of median-innervated fingers. There was no correlation between
      median neuropathy and conventional radiographic parameters. Surprisingly, the
      cross-sectional area of the carpal canal was significantly greater for patients
      with median neuropathy. Symptoms resolved in all patients after corrective
      osteotomy. Postoperatively, six of ten patients demonstrated improved nerve
      conduction studies, although only four patients demonstrated normal test results.
      DISCUSSION: There is a high rate of subclinical median neuropathy in malunited
      distal radial fractures that cannot be predicted by conventional radiographic
      parameters. Corrective osteotomy without carpal tunnel release is a sufficient
      treatment for neuropathy in malunited distal radius fractures.

PMID- 23864158
TI  - Long-term survival of GSB III elbow prostheses and risk factors for revisions.
AB  - INTRODUCTION: Although replacement of the elbow joint is a complex procedure
      there is not much clinical evidence that contributes to surgical decision-making,
      mainly due to small clinical samples and short follow-up. Therefore, we performed
      a long-term analysis up to 30 years after implantation of a GSB III total elbow
      prosthesis to quantify long-term outcome and to identify possible risk factors
      for implant revision. MATERIALS AND METHODS: All patients who received a primary
      GSB III total elbow prosthesis between 1978 and 1998 were included. Information
      about patient characteristics, the latest known implant status and possible risk
      factors were collected, Kaplan-Meier survival curves plotted, and 10- and 20-year
      survival calculated. The cohort was stratified for known risk factors such as
      diagnosis, age, or gender and included in a Cox regression analysis. RESULTS: A
      total of 253 patients [mean age at operation 56.9 years (range from 17.5 to 84
      years)] with 293 GSB III prostheses were included. The median follow-up was 9.1
      years (0 months to 29.3 years). Whereas 81 prostheses did not need revision
      during the observation period, 76 had been implanted in patients who died before
      any revision was required, and 75 had not been revised by the last known follow
      up. 61 prostheses were revised. This corresponds to a 10-year survival rate of
      0.8 (95 % CI 0.74-0.85) and a 20-year rate of 0.67 (95 % CI 0.57-0.76).
      Prostheses in patients with post-traumatic conditions survived significantly
      shorter than those in patients with rheumatoid arthritis; previous operations
      lead to a 2.8 times greater risk of revision (p = 0.004). Neither age at
      implantation nor gender had a significant influence on prosthesis survival.
      CONCLUSIONS: The results indicate a good long-term prognosis for this design. The
      prognosis has to be adjusted for the underlying disease. Previous operations such
      as joint reconstruction significantly increase the risk of revision.

PMID- 23864159
TI  - Dendritic Au/TiO2 nanorod arrays for visible-light driven photoelectrochemical
      water splitting.
AB  - This paper describes the synthesis of TiO2 branched nanorod arrays (TiO2 BNRs)
      with plasmonic Au nanoparticles attached on the surface. Such Au/TiO2 BNR
      composites exhibit high photocatalytic activity in photoelectrochemical (PEC)
      water splitting. The unique structure of Au/TiO2 BNRs shows enhanced activity
      with a photocurrent of 0.125 mA cm(-2) under visible light (>=420 nm) and 2.32 +/
      0.1 mA cm(-2) under AM 1.5 G illumination (100 mW cm(-2)). The obtained
      photocurrent is comparable to the highest value ever reported. Furthermore, the
      Au/TiO2 BNRs achieve the highest efficiency of ~1.27% at a low bias of 0.50 V vs.
      RHE, indicating elevated charge separation and transportation efficiencies. The
      high PEC performance is mainly due to the plasmonic effect of Au nanoparticles,
      which enhances the visible light absorption, together with the large surface
      area, efficient charge separation and high carrier mobility of the TiO2 BNRs. The
      carrier density of Au/TiO2 BNRs is nearly 6 times higher than the pristine TiO2
      BNRs as calculated by the Mott-Schottky plot. Based on the analysis by UV-Vis
      spectroscopy, electrochemical impedance spectroscopy, and photoluminescence, a
      mechanism was proposed to explain the high activity of Au/TiO2 BNRs in PEC water
      splitting. The capability of synthesizing highly visible light active Au/TiO2 BNR
      based photocatalysts is useful for solar conversion applications, such as PEC
      water splitting, dye-sensitized solar cells and photovoltaic devices.

PMID- 23864160
TI  - Gray matter abnormalities as brain structural vulnerability factors for bipolar
      disorder: A review of neuroimaging studies of individuals at high genetic risk
      for bipolar disorder.
AB  - OBJECTIVE: Cortical and subcortical gray matter abnormalities have been reported
      in individuals at high genetic risk for bipolar disorder, but the findings are
      inconsistent. The aim of this study was to review the available literature to
      identify common findings that could represent brain structural vulnerability
      factors for bipolar disorder and to discuss challenges for the advancement of the
      field. METHOD: A systematic search was conducted using the PubMed database to
      identify all original articles investigating cortical or subcortical gray matter
      abnormalities in first-degree relatives of bipolar disorder patients. RESULTS:
      Very few findings were replicated, with the exception of larger insular cortex
      volumes in adult first-degree relatives and larger right inferior frontal gyrus
      in offspring of probands with bipolar disorder, both when compared with healthy
      controls. Isolated findings included decreased gray matter density in the left
      thalamus, decreased gray matter volumes in the left hippocampus and
      parahippocampal gyrus, and thicker right hippocampus in unaffected first-degree
      relatives. Genetic liability for bipolar disorder was associated with gray matter
      volumes in regions of the anterior cingulate cortex, ventral striatum, medial
      frontal gyrus, right precentral gyrus, right insular cortex, and medial orbital
      gyrus. Some studies found no evidence for gray matter abnormalities in first
      degree relatives of bipolar disorder patients. CONCLUSIONS: Possible reasons for
      the discrepancies of findings across studies include small samples sizes, small
      effect size of susceptibility genes, the phenotypic heterogeneity of bipolar
      disorder, and the possible confounding effect of other Axis I psychopathologies
      among the relatives of patients. Future multisite, prospective, large studies
      with more homogeneous samples would be a key strategy to advance the field. The
      ultimate benefit would be an understanding of how to use brain imaging tools to
      identify individuals at increased risk for bipolar disorder and develop
      preventive strategies for that population.

PMID- 23864161
TI  - Risk preferences: consequences for test and treatment thresholds and optimal
      cutoffs.
AB  - Risk attitudes include risk aversion as well as higher-order risk preferences
      such as prudence and temperance. This article analyzes the effects of such
      preferences on medical test and treatment decisions, represented either by test
      and treatment thresholds or-when the test result is not given-by optimal cutoff
      values for diagnostic tests. For a risk-averse decision maker, effective
      treatment is a risk-reducing strategy since it prevents the low health outcome of
      forgoing treatment in the sick state. Compared with risk neutrality, risk
      aversion thus lowers both the test and the treatment threshold and decreases the
      optimal test cutoff value. Risk vulnerability, which combines risk aversion,
      prudence, and temperance, is relevant if there is a comorbidity risk: thresholds
      and optimal cutoff values decrease even more. Since common utility functions
      imply risk vulnerability, our findings suggest that diagnostics in low prevalence
      settings (e.g., screening) may be considered more beneficial when risk
      preferences are taken into account.

PMID- 23864162
TI  - Polychlorinated biphenyl concentrations and activity of sea lamprey Petromyzon
      marinus vary by sex.
AB  - We determined the polychlorinated biphenyl (PCB) concentrations of 40 male and 40
      female adult sea lampreys Petromyzon marinus captured in the Cheboygan River, a
      tributary to Lake Huron, during May 2011. In addition, we performed a laboratory
      experiment using passive integrated transponder tags to determine whether male
      adult sea lampreys were more active than female adult sea lampreys. Sex had a
      significant effect on PCB concentration, and PCB concentration at a given level
      of sea lamprey condition was approximately 25 % greater in males than in females.
      Adjusting for the difference in condition between the sexes, males averaged a 17
      % greater PCB concentration compared with females. Results from the laboratory
      experiment indicated that males were significantly more active than females. The
      observed sex difference in PCB concentrations was not due to female sea lampreys
      releasing eggs at spawning because the sea lamprey is semelparous, and we caught
      the sea lampreys before spawning. Rather, we attributed the sex difference in PCB
      concentrations to a greater rate of energy expenditure in males compared with
      females. We proposed that this greater rate of energy expenditure was likely due
      to greater activity. Our laboratory experiment results supported this hypothesis.
      A greater resting metabolic rate may also have contributed to a greater rate of
      energy expenditure. Our findings should eventually be applicable toward improving
      control of sea lamprey, a pest responsible for considerable damage to fisheries
      in lakes where it is not native. 

PMID- 23864163
TI  - Tumor-specific T-cell help is associated with improved survival in melanoma.
AB  - Despite success with immune checkpoint inhibitors, clinical benefit from cancer
      vaccines remains elusive. Combined targeting of melanoma-specific CD4(+) and
      CD8(+) T-lymphocyte epitopes was associated with improved survival compared with
      targeting either alone, or when a nonspecific helper epitope was used. We discuss
      the potential role of antigen-specific CD4 help.

PMID- 23864164
TI  - Dual targeting of wild-type and mutant p53 by small molecule RITA results in the
      inhibition of N-Myc and key survival oncogenes and kills neuroblastoma cells in
      vivo and in vitro.
AB  - PURPOSE: Restoration of the p53 function in tumors is a promising therapeutic
      strategy due to the high potential of p53 as tumor suppressor and the fact that
      established tumors depend on p53 inactivation for their survival. Here, we
      addressed the question whether small molecule RITA can reactivate p53 in
      neuroblastoma and suppress the growth of neuroblastoma cells in vitro and in
      vivo. EXPERIMENTAL DESIGN: The ability of RITA to inhibit growth and to induce
      apoptosis was shown in seven neuroblastoma cell lines. Mechanistic studies were
      carried out to determine the p53 dependence and the molecular mechanism of RITA
      induced apoptosis in neuroblastoma, using cell viability assays, RNAi silencing,
      co-immunoprecipitation, qPCR, and Western blotting analysis. In vivo experiments
      were conducted to study the effect of RITA on human neuroblastoma xenografts in
      mice. RESULTS: RITA induced p53-dependent apoptosis in a set of seven
      neuroblastoma cell lines, carrying wild-type or mutant p53; it activated p53 and
      triggered the expression of proapoptotic p53 target genes. Importantly, p53
      activated by RITA inhibited several key oncogenes that are high-priority targets
      for pharmacologic anticancer strategies in neuroblastoma, including N-Myc, Aurora
      kinase, Mcl-1, Bcl-2, Wip-1, MDM2, and MDMX. Moreover, RITA had a strong
      antitumor effect in vivo. CONCLUSIONS: Reactivation of wild-type and mutant p53
      resulting in the induction of proapoptotic factors along with ablation of key
      oncogenes by compounds such as RITA may be a highly effective strategy to treat
      neuroblastoma.

PMID- 23864167
TI  - Registration-based reconstruction of four-dimensional cone beam computed
      tomography.
AB  - We present a new method for reconstruction of 4-D cone beam computed tomography
      from an undersampled set of X-ray projections. The novelty of the proposed method
      lies in utilizing optical flow based registration to facilitate that each
      temporal phase is reconstructed from the full set of acquired projections. The
      reconstruction of each phase thus exhibits limited aliasing despite significant
      intra-phase undersampling. The method is fully self-contained. Initially an
      approximate 4-D volume is reconstructed and an inter-phase registration based
      hereon. A subsequent reconstruction pass integrates the optical flow estimation
      in a cost function formulation in which the X-ray projections from all temporal
      phases are considered for the reconstruction of each individual phase.
      Quantitative and qualitative evaluations were performed through reconstruction of
      both a numerical phantom and a clinical dataset. The obtained reconstructions are
      compared to the state-of-the-art alternatives of total variation regularization
      and prior image constrained compressed sensing. Our studies show that the
      proposed method is the better overall "compromise" in the depiction of both
      moving and stationary anatomical structures. 

PMID- 23864166
TI  - Modeling and molecular dynamics of the intrinsically disordered e7 proteins from
      high- and low-risk types of human papillomavirus.
AB  - Cervical cancer affects millions of women worldwide each year. Most cases of
      cervical cancer are caused by the sexually transmitted human papillomavirus
      (HPV). The approximately 40 HPV types that infect the cervix are designated high-
      or low-risk based on their potential to lead to high-grade lesions and cancer.
      The HPV E7 oncoprotein is directly involved in the onset of cervical cancer and
      associates with the pRb protein and other cellular targets that promote cell
      immortalization and carcinogenesis. This is the first description of the modeling
      and molecular dynamics analysis of complete three-dimensional structures of high
      risk (HPV types 16 and 18), low-risk (HPV type 11), and HPV type 01 E7 proteins.
      The models were constructed by a hybrid approach using homology (MODELLER) and ab
      initio (Rosetta) modeling, and the protein dynamics were simulated for 50 ns
      under normal pressure and temperature (NPT) conditions. The intrinsic disorder of
      the E7 protein sequence was assessed in silico. Complete models of E7 were
      obtained despite the predicted intrinsic disorder of the N-termini from the high
      risk HPV types. The N-terminal domains of all of the E7 proteins studied, even
      those from high-risk strains, exhibited secondary structure after modeling.
      Trajectory analysis of E7 proteins from HPV types 16 and 18 showed higher
      instability in their N-terminal domains than in those of HPV types 11 and 01;
      however, this variation did not affect the secondary structure during the
      simulation. ANCHOR analysis indicated that the CR1 and CR2 regions of HPV types
      16 and 18 contain possible targets for future drug-discovery studies.

PMID- 23864165
TI  - Tumor-infiltrating lymphocytes in glioblastoma are associated with specific
      genomic alterations and related to transcriptional class.
AB  - PURPOSE: Tumor-infiltrating lymphocytes (TIL) have prognostic significance in
      many cancers, yet their roles in glioblastoma have not been fully defined. We
      hypothesized that TILs in glioblastoma are associated with molecular alterations,
      histologies, and survival. EXPERIMENTAL DESIGN: We used data from The Cancer
      Genome Atlas (TCGA) to investigate molecular, histologic, and clinical correlates
      of TILs in glioblastomas. Lymphocytes were categorized as absent, present, or
      abundant in histopathologic images from 171 TCGA glioblastomas. Associations were
      examined between lymphocytes and histologic features, mutations, copy number
      alterations, CpG island methylator phenotype, transcriptional class, and
      survival. We validated histologic findings using CD3G gene expression. RESULTS:
      We found a positive correlation between TILs and glioblastomas with gemistocytes,
      sarcomatous cells, epithelioid cells, and giant cells. Lymphocytes were enriched
      in the mesenchymal transcriptional class and strongly associated with mutations
      in NF1 and RB1. These mutations are frequent in the mesenchymal class and
      characteristic of gemistocytic, sarcomatous, epithelioid, and giant cell
      histologies. Conversely, TILs were rare in glioblastomas with small cells and
      oligodendroglioma components. Lymphocytes were depleted in the classical
      transcriptional class and in EGF receptor (EGFR)-amplified and homozygous PTEN
      deleted glioblastomas. These alterations are characteristic of glioblastomas with
      small cells and glioblastomas of the classical transcriptional class. No
      association with survival was shown. CONCLUSIONS: TILs were enriched in
      glioblastomas of the mesenchymal class, strongly associated with mutations in NF1
      and RB1 and typical of histologies characterized by these mutations. Conversely,
      TILs were depleted in the classical class, EGFR-amplified, and homozygous PTEN
      deleted tumors and rare in histologies characterized by these alterations.

PMID- 23864168
TI  - From connectivity models to region labels: identifying foci of a neurological
      disorder.
AB  - We propose a novel approach to identify the foci of a neurological disorder based
      on anatomical and functional connectivity information. Specifically, we formulate
      a generative model that characterizes the network of abnormal functional
      connectivity emanating from the affected foci. This allows us to aggregate
      pairwise connectivity changes into a region-based representation of the disease.
      We employ the variational expectation-maximization algorithm to fit the model and
      subsequently identify both the afflicted regions and the differences in
      connectivity induced by the disorder. We demonstrate our method on a population
      study of schizophrenia. 

PMID- 23864170
TI  - What do we miss? ASAS non-responders on anti-TNF therapy show improvement in
      performance-based physical function.
AB  - OBJECTIVE: A prospective study was conducted in order to establish whether AS
      patients, who are defined as non-responders after 3 months of anti-TNF therapy,
      show improvement on performance-based tests of physical functioning. METHODS: At
      baseline and 3 months after the start of anti-TNF therapy, AS patients completed
      seven performance-based tests of physical functioning, questionnaires on self
      reported physical functioning (BASFI) and disease activity (BASDAI), and a pain
      and a global patient assessment. The concordance between >= 20% intra-individual
      improvement on the performance-based test of physical functioning and (i)
      response to anti-TNF therapy [Assessment of SpondyloArthritis International
      Society 20% (ASAS20) response] and (ii) >= 20% intra-individual improvement on
      self-reported physical functioning (BASFI) was assessed. RESULTS: One hundred AS
      patients were included, of which 82 patients completed all tests at both time
      points. After 3 months of anti-TNF therapy, 27 (32.9%) patients were categorized
      as non-responders according to the ASAS20 response criteria. Improvement in
      performance-based physical functioning was seen in 13 of the 27 non-responders
      (48.1%) (i.e. n = 13/82 = 15.9% of the total group). Furthermore, 30 (36.6%)
      patients showed no improvement on self-reported physical functioning (BASFI).
      However, 17 of the 30 (56.7%) patients did improve on the performance-based tests
      of physical functioning (i.e. n = 17/82 = 20.7% of the total group). CONCLUSION:
      After 3 months of anti-TNF therapy, performance-based tests of physical
      functioning showed improvement in 48.1% of the ASAS20 non-responders. With these
      performance-based tests, new information on outcome after anti-TNF therapy can be
      generated. Using performance-based tests alongside the BASFI could have
      additional value in the evaluation of outcomes for patients receiving anti-TNF
      therapy.

PMID- 23864169
TI  - GUEPARD treat-to-target strategy is significantly more efficacious than ESPOIR
      routine care in early rheumatoid arthritis according to patient-reported outcomes
      and physician global estimate.
AB  - OBJECTIVE: To analyse seven RA Core Data Set measures and three indices for their
      capacity to distinguish treatment results in early RA in the GUEPARD treat-to
      target clinical trial vs ESPOIR routine care. METHODS: Post hoc analyses compared
      65 GUEPARD and 130 matched control ESPOIR patients over 6 and 12 months for mean
      changes in measures, relative efficiencies and standardized response means (SRM).
      Three indices-28-joint disease activity score (DAS28), clinical disease activity
      index (CDAI) and routine assessment of patient index data (RAPID3)-were compared
      for mean changes and numbers of patients with high, moderate or low activity or
      remission using kappa values. RESULTS: Greater improvement was seen for GUEPARD
      vs ESPOIR, statistically significant for physician and patient global estimates
      and pain and health assessment questionnaire physical function (HAQ-FN), but not
      joint counts and laboratory tests. Relative efficiencies with tender joint count
      as the referent measure indicated that pain (2.57) and global estimates by
      patient (3.13) and physician (2.31) were most efficient in distinguishing GUEPARD
      from ESPOIR. Mean improvements in GUEPARD vs ESPOIR were -3.4 vs -2.6 for DAS28
      (0-10) (24%), -29.8 vs -23.1 for CDAI (0-76) (23%) and -13.0 vs -7.8 for RAPID3
      (0-30) (40%) (all P < 0.01); agreement was moderate between CDAI vs DAS28 (kappa
      = 0.56) and vs RAPID3 (kappa = 0.48), and fair between DAS28 vs RAPID3 (kappa =
      0.26). CONCLUSION: Patient and global measures indicate greater efficacy than
      joint counts or laboratory measures in detecting difference between GUEPARD treat
      to-target and ESPOIR routine care. A RAPID3 of only patient measures may help
      guide treat-to-target in busy clinical settings.

PMID- 23864171
TI  - Biologic treatments for adult-onset Still's disease.
AB  - Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder that is a
      diagnosis of exclusion. It is characterized by high spiking fevers, arthritis or
      arthralgia, and an evanescent salmon-coloured rash. Many other systemic
      manifestations and laboratory test abnormalities may occur. Biologic drugs, TNF
      alpha inhibitors, and IL-1 and IL-6 blockers have been used for the treatment of
      patients with AOSD refractory to conventional treatment or those with life
      threatening manifestations aiming for better disease control. Data on biologic
      treatments in AOSD are limited and consist mainly of case reports, small case
      series and retrospective studies. Using biologic agents (anti-TNF-alpha, anti-IL
      1 and anti-IL-6) with traditional immunosuppressive drugs resulted in significant
      improvement of disease outcomes. IL-1 and IL-6 inhibitors seem to be more
      efficient than TNF-alpha inhibitors. 

PMID- 23864172
TI  - The natural history of asymptomatic rotator cuff tears: a three-year follow-up of
      fifty cases.
AB  - BACKGROUND: Little is known about the clinical and anatomic progression of
      asymptomatic rotator cuff tears. The purpose of our study was to assess if
      deterioration in rotator cuff tear anatomy would be correlated to the development
      of symptoms. METHODS: Fifty patients with initially asymptomatic full-thickness
      rotator cuff tears were followed clinically, sonographically, and by magnetic
      resonance imaging over three years. Changes of tear size, muscle atrophy, fatty
      degeneration, and condition of the long head of the biceps tendon were compared
      between tears that developed symptoms and those that did not. RESULTS: Eighteen
      of fifty tears developed symptoms during follow-up. There was a significantly
      larger increase (p = 0.02) in the mean tear size in the newly symptomatic group
      (10.6 mm) when compared with the still-asymptomatic group (3.3 mm). The rate of
      progressing to advanced muscle atrophy was higher (p = 0.08) in the newly
      symptomatic group (35% [six of seventeen subjects]) when compared with the still
      asymptomatic group (12% [three of twenty-five subjects]). The rate of fatty
      degeneration was significantly higher (p = 0.02) in the newly symptomatic group
      (35% [six of seventeen subjects]) when compared with the still-asymptomatic group
      (4% [one of twenty-five subjects]). The rate of pathology of the long head of the
      biceps tendon was significantly higher (p = 0.02) in the newly symptomatic group
      (33% [six of eighteen subjects]) when compared with the still-asymptomatic group
      (6% [two of thirty-two subjects]). CONCLUSIONS: During a relatively short-term
      follow-up, a substantial percentage of asymptomatic rotator cuff tears became
      symptomatic and underwent anatomic deterioration. Increase in tear size and
      decrease of muscle quality were correlated to the development of symptoms.
      Subjects diagnosed with an asymptomatic rotator cuff tear should be informed
      about the natural history of the condition and follow-up with repeated imaging
      may be indicated to monitor tear progression.

PMID- 23864173
TI  - Cost-effectiveness of low-molecular-weight heparin compared with aspirin for
      prophylaxis against venous thromboembolism after total joint arthroplasty.
AB  - BACKGROUND: There is controversy regarding the most appropriate strategy to
      prevent venous thromboembolism following total joint arthroplasty. Our objective
      was to estimate the lifetime costs, quality-adjusted life-years (QALYs), and
      costs per QALY gained using low-molecular-weight heparin compared with low-dose
      aspirin for two weeks after total knee or total hip arthroplasty in patients with
      no history of venous thromboembolism. METHODS: We used a Markov cohort model with
      health states of healthy after surgery, no postphlebitic syndrome after venous
      thromboembolism, postphlebitic syndrome after venous thromboembolism, and
      survival after intracranial hemorrhage to compare treatment with low-molecular
      weight heparin or aspirin (160 mg) for fourteen days after total knee
      arthroplasty or total hip arthroplasty in patients with an age of fifty-five,
      sixty, sixty-five, seventy, seventy-five, eighty, or eighty-five years. We
      estimated lifetime costs, QALYs gained, and costs per QALY gained for both
      strategies, and applied a cost-effectiveness threshold of $100,000 (2010 U.S.
      dollars) per QALY gained. RESULTS: For patients undergoing total hip arthroplasty
      at the ages of fifty-five and seventy years, costs per QALY gained for low
      molecular-weight heparin compared with aspirin were $315,000 and $1.4 million,
      respectively. For those undergoing total hip arthroplasty at the age of eighty or
      eighty-five years, aspirin cost less and saved more QALYs than low-molecular
      weight heparin. For patients undergoing total knee arthroplasty at the ages of
      fifty-five, seventy, and eighty-five years, costs per QALY gained with low
      molecular-weight heparin were $36,000, $112,000, and $448,000, respectively.
      Probabilistic sensitivity analyses confirmed a low probability of low-molecular
      weight heparin being cost-effective for patients undergoing total hip
      arthroplasty and for those with an age of eighty years or older undergoing total
      knee arthroplasty. For individuals younger than eighty years of age undergoing
      total knee arthroplasty, the cost-effectiveness of low-molecular-weight heparin
      compared with aspirin is uncertain. CONCLUSIONS: For patients with no history of
      venous thromboembolism, aspirin is a cost-effective choice for venous
      thromboembolism prophylaxis following total hip arthroplasty, but the preferred
      choice following total knee arthroplasty depends on age and is uncertain for
      those younger than eighty years old.

PMID- 23864174
TI  - Factors associated with use of bone morphogenetic protein during pediatric spinal
      fusion surgery: an analysis of 4817 patients.
AB  - BACKGROUND: Our goal was to investigate whether the use of recombinant human bone
      morphogenetic protein (rhBMP, or BMP) during pediatric spinal fusion surgery has
      been increasing and how patient, surgical, and hospital characteristics influence
      BMP use. METHODS: Using the Nationwide Inpatient Sample database, we identified
      4817 children eighteen years old or younger who had undergone spinal fusion
      surgery with the use of BMP from 2003 through 2009. A multivariate logistic
      regression model, the Z-test of proportions, and simple linear regression were
      used for statistical analysis (significance, p < 0.05). RESULTS: There was a 3.4
      fold increase in BMP use, from 2.7% in 2003 to 9.3% in 2009-an average 16% per
      year increase (p < 0.01). For each additional year of age, BMP use increased 1.09
      fold (odds ratio [OR]: 1.05 to 1.13, p < 0.01). Compared with BMP use for
      adolescent idiopathic scoliosis, the adjusted odds of BMP use were increased 1.3
      fold for congenital scoliosis (OR: 1.02 to 1.76, p = 0.04), 2.8-fold for
      thoracolumbar fractures (OR: 2.1 to 3.8, p < 0.01), and 5.0-fold for
      spondylolisthesis (OR: 3.9 to 6.3, p < 0.01). Patients with private insurance
      were 1.5-fold more likely to receive BMP (OR: 1.2 to 1.9, p < 0.01). Patients in
      whom autograft bone was used intraoperatively were 0.63-fold less likely to
      receive BMP (OR: 0.52 to 0.77, p < 0.01). The rate of BMP use was 0.38-fold lower
      in teaching hospitals (OR: 0.31 to 0.48, p < 0.01) and 1.7-fold higher in
      hospitals with a large bed capacity (OR: 1.3 to 2.2, p < 0.01). Compared with
      hospitals located in the Northeast, those in the West had a 1.7-fold increase
      (OR: 1.3 to 2.4, p < 0.01) and those in the South had a 2.0-fold increase (OR:
      1.5 to 2.7, p < 0.01) in the odds of BMP use. CONCLUSIONS: Use of BMP during
      pediatric spinal fusion has increased significantly. Patient factors (age,
      diagnosis, and insurance), surgical factors (autograft use), and hospital factors
      (teaching status, bed capacity, and location) influenced the variation in BMP
      use.

PMID- 23864175
TI  - Comparison of functional outcome measures after ACL reconstruction in competitive
      soccer players: a randomized trial.
AB  - BACKGROUND: The choice of graft for anterior cruciate ligament (ACL)
      reconstruction remains controversial. Although many outcome studies comparing
      bone-patellar tendon-bone and semitendinosus and gracilis tendon grafts have been
      performed, most have not included tests of functional outcomes that challenge the
      graft. The objective of the current study was to compare the functional
      performances of soccer players after ACL reconstruction that was performed with
      either a bone-patellar tendon-bone or a semitendinosus and gracilis tendon graft.
      METHODS: Forty-two soccer players with unilateral ACL injury were prospectively
      randomized to a bone-patellar tendon-bone group (BPTB group; twenty-one subjects)
      or a semitendinosus and gracilis tendon group (STG group; twenty-one subjects)
      and followed a rehabilitation protocol. At the time of return to sports, the
      patients were asked to execute strength, hop, and jump tests and the results were
      compared between the groups. Twenty-one healthy athletes were recruited as the
      control group to evaluate their performance of the same tests. RESULTS: The limbs
      with the ACL reconstruction in the STG group had greater values for quadriceps
      torque as well as on the triple-hop, crossover-hop, and jump-landing test (p <
      0.01), but the STG and BPTB groups showed similar results in terms of hamstrings
      peak torque and the results of two other hop tests (p > 0.05). Moreover, the
      subjects with ACL reconstruction had significantly lower values with regard to
      quadriceps and hamstrings peak torques and the results of the hop and jump tests
      compared with the healthy athletes (p < 0.01). CONCLUSIONS: At the time of return
      to sports, the STG group had better performance in terms of quadriceps strength
      and the results of the triple-hop, crossover-hop, and jump-landing tests compared
      with the BPTB group. Compared with controls, soccer players who had undergone ACL
      reconstruction had less quadriceps and hamstrings strength and inferior hop
      performance and jump-landing strategy.

PMID- 23864177
TI  - Clinical and radiographic outcomes of total shoulder arthroplasty with bone graft
      for osteoarthritis with severe glenoid bone loss.
AB  - BACKGROUND: Glenohumeral osteoarthritis may be associated with severe posterior
      glenoid bone loss and glenoid retroversion. Treatment with total shoulder
      arthroplasty and autologous bone graft obtained from the humeral head has been
      infrequently reported in the peer-reviewed literature. METHODS: The clinical and
      radiographic results of primary total shoulder replacement with an all
      polyethylene glenoid component and autologous humeral head graft augmentation
      performed by a single surgeon in thirteen consecutive patients were evaluated.
      RESULTS: Twelve of the thirteen patients were followed for a minimum of two years
      (average, fifty-three months; range, twenty-six to 110 months). The average
      glenoid retroversion on preoperative computed tomography (CT) scans was 44
      degrees  (range, 20 degrees  to 65 degrees ). Based on the Walch classification
      of pathologic glenoid morphology, nine glenoids were B2 and three were type C.
      All patients had an intact cuff at the time of surgery. At the time of the last
      follow up, ten of the twelve patients had graft incorporation without any
      resorbtion and two had minor bone graft resorption. Broken screws occurred in two
      of these ten cases. Two patients, both of whom required revision surgery, had
      failure of fixation and of graft incorporation; one of these failures was due to
      early postoperative trauma and the other, to Propionibacterium acnes infection.
      CONCLUSIONS: The early and midterm results of total shoulder arthroplasty with
      autogenous bone graft demonstrated substantial clinical and radiographic
      improvement in most cases.

PMID- 23864176
TI  - Wnt3a reestablishes osteogenic capacity to bone grafts from aged animals.
AB  - BACKGROUND: Age-related fatty degeneration of the bone marrow contributes to
      delayed fracture-healing and osteoporosis-related fractures in the elderly. The
      mechanisms underlying this fatty change are unknown, but they may relate to the
      level of Wnt signaling within the aged marrow cavity. METHODS: Transgenic mice
      were used in conjunction with a syngeneic bone-graft model to follow the fates of
      cells involved in the engraftment. Immunohistochemistry along with quantitative
      assays were used to evaluate Wnt signaling and adipogenic and osteogenic gene
      expression in bone grafts from young and aged mice. Liposomal Wnt3a protein (L
      Wnt3a) was tested for its ability to restore osteogenic potential to aged bone
      grafts in critical-size defect models created in mice and in rabbits.
      Radiography, microquantitative computed tomography (micro-CT) reconstruction,
      histology, and histomorphometric measurements were used to quantify bone-healing
      resulting from L-Wnt3a or a control substance (liposomal phosphate-buffered
      saline solution [L-PBS]). RESULTS: Expression profiling of cells in a bone graft
      demonstrated a shift away from an osteogenic gene profile and toward an
      adipogenic one with age. This age-related adipogenic shift was accompanied by a
      significant reduction (p < 0.05) in Wnt signaling and a loss in osteogenic
      potential. In both large and small animal models, osteogenic competence was
      restored to aged bone grafts by a brief incubation with the stem-cell factor
      Wnt3a. In addition, liposomal Wnt3a significantly reduced cell death in the bone
      graft, resulting in significantly more osseous regenerate in comparison with
      controls. CONCLUSIONS: Liposomal Wnt3a enhances cell survival and reestablishes
      the osteogenic capacity of bone grafts from aged animals. CLINICAL RELEVANCE: We
      developed an effective, clinically applicable, regenerative medicine-based
      strategy for revitalizing bone grafts from aged patients.

PMID- 23864178
TI  - Reverse total shoulder arthroplasty for primary glenohumeral osteoarthritis in
      patients with a biconcave glenoid.
AB  - BACKGROUND: The biconcave glenoid in patients with primary glenohumeral
      osteoarthritis represents a surgical challenge because of the associated static
      posterior instability of the humeral head and secondary posterior glenoid
      erosion. The purpose of the present study was to evaluate the clinical and
      radiographic results of reverse total shoulder arthroplasty for the treatment of
      primary osteoarthritis in patients with a biconcave glenoid without rotator cuff
      insufficiency. METHODS: We performed a retrospective review of twenty-seven
      reverse shoulder arthroplasties that were performed from 1998 to 2009 for the
      treatment of primary glenohumeral osteoarthritis and biconcave glenoid. Eighty
      one percent of the patients were female, and the mean age of the patients at the
      time of surgery was 74.1 years (range, sixty-six to eighty-two years). All
      patients had a preoperative computed tomography arthrogram to allow for the
      measurement of glenoid retroversion and humeral head subluxation. The mean
      preoperative retroversion was 32 degrees , and the mean subluxation of the
      humeral head with respect to the scapular axis was 87%. Seventeen patients had a
      reverse shoulder arthroplasty without bone graft, whereas ten had an associated
      bone graft to compensate for posterior glenoid erosion. Clinical outcomes were
      evaluated with the Constant score and shoulder range of motion. RESULTS: The mean
      duration of follow-up was fifty-four months (range, twenty-four to 139 months).
      The mean Constant score increased from 31 points preoperatively to 76 points at
      the time of the latest follow-up (p < 0.0001). Active forward flexion, external
      rotation, and internal rotation also significantly increased (p < 0.0001).
      Complications occurred in four patients (15%) and included early loosening of the
      glenoid component (one patient) and neurologic complications (three patients). No
      radiolucent lines were observed around the central peg or screws of the glenoid
      component. Grade-1 or 2 scapular notching was present in ten shoulders (37%). No
      recurrence of posterior instability was observed. CONCLUSIONS: Reverse shoulder
      arthroplasty for the treatment of primary glenohumeral osteoarthritis in patients
      with a biconcave glenoid without rotator cuff insufficiency can result in
      excellent clinical outcomes. Reverse shoulder arthroplasty is a viable surgical
      option to solve both the problem of severe static posterior glenohumeral
      instability and severe glenoid erosion.

PMID- 23864179
TI  - Leaded eyeglasses substantially reduce radiation exposure of the surgeon's eyes
      during acquisition of typical fluoroscopic views of the hip and pelvis.
AB  - BACKGROUND: Despite recommendations to do so, few orthopaedists wear leaded
      glasses when performing operative fluoroscopy. Radiation exposure to the ocular
      lens causes cataracts, and regulatory limits for maximum annual occupational
      exposure to the eye continue to be revised downward. METHODS: Using
      anthropomorphic patient and surgeon phantoms, radiation dose at the surgeon
      phantom's lens was measured with and without leaded glasses during fluoroscopic
      acquisition of sixteen common pelvic and hip views. The magnitude of lens dose
      reduction from leaded glasses was calculated by dividing the unprotected dose by
      the dose measured behind leaded glasses. RESULTS: On average, the use of leaded
      glasses reduced radiation to the surgeon phantom's eye by tenfold, a 90%
      reduction in dose. However, there was widespread variation in the amount of
      radiation that reached the phantom surgeon's eye among the various radiographic
      projections we studied. Without leaded glasses, the dose measured at the
      surgeon's lens varied more than 250-fold among these sixteen different views.
      CONCLUSIONS: In addition to protecting the surgeon's eye from the deleterious
      effects of radiation, the use of leaded glasses could permit an orthopaedist to
      perform fluoroscopic views on up to ten times more patients before reaching the
      annual dose limit of 20 mSv of radiation to the eye recommended by the
      International Commission on Radiological Protection. Personal safety and
      adherence to limits of occupational radiation exposure should compel
      orthopaedists to wear leaded glasses for fluoroscopic procedures if other
      protective barriers are not in use. CLINICAL RELEVANCE: Leaded glasses are a
      powerful tool for reducing the orthopaedic surgeon's lens exposure to radiation
      during acquisition of common intraoperative fluoroscopic views.

PMID- 23864180
TI  - Quantitative assessment of the yield of osteoblastic connective tissue
      progenitors in bone marrow aspirate from the iliac crest, tibia, and calcaneus.
AB  - BACKGROUND: It is well known that bone marrow aspirate from the iliac crest
      contains osteoblastic connective tissue progenitor cells. Alternative harvest
      sites in foot and ankle surgery include the distal aspect of the tibia and the
      calcaneus. To our knowledge, no previous studies have characterized the quality
      of bone marrow aspirate obtained from these alternative sites and compared the
      results with those of aspirate from the iliac crest. The goal of this study was
      to determine which anatomic location yields the highest number of osteoblastic
      progenitor cells. METHODS: Forty patients were prospectively enrolled in the
      study, and separate bone marrow aspirate samples were harvested from the
      ipsilateral anterior iliac crest, distal tibial metaphysis, and calcaneal body.
      The aspirate was centrifuged to obtain a concentrate of nucleated cells, which
      were plated and grown in cell culture. Colonies that stained positive for
      alkaline phosphatase were counted to estimate the number of osteoblastic
      progenitor cells in the initial sample. The anatomic locations were compared.
      Clinical parameters (including sex, age, tobacco use, body mass index, and
      diabetes) were assessed as possible predictors of osteoblastic progenitor cell
      yield. RESULTS: Osteoblastic progenitor cells were found at each anatomic
      location. Bone marrow aspirate collected from the iliac crest had a higher mean
      concentration of osteoblastic progenitor cells compared with the distal aspect of
      the tibia or the calcaneus (p < 0.0001). There was no significant difference in
      concentration between the tibia and the calcaneus (p = 0.063). Age, sex, tobacco
      use, and diabetes were not predictive of osteoblastic progenitor cell yield.
      CONCLUSIONS: Osteoblastic progenitor cells are available in the iliac crest,
      proximal aspect of the tibia, and calcaneus. However, the iliac crest provided
      the highest yield of osteoblastic progenitor cells. CLINICAL RELEVANCE: The study
      demonstrated that osteogenic progenitor cells are available in bone marrow
      aspirate harvested from the tibia or calcaneus as well as the iliac crest. All
      three sites are easily accessed, with a low risk of adverse events. However,
      larger volumes of aspirate may be needed from the tibia or calcaneus to approach
      the yield of cells from the iliac crest.

PMID- 23864181
TI  - Interscalene brachial plexus block for arthroscopic shoulder surgery: a
      systematic review.

PMID- 23864183
TI  - Overcoming resistance to implementation of integrated care pathways in
      orthopaedics.
AB  - The future of orthopaedic surgery will be shaped by unprecedented demographic and
      economic challenges, necessitating movement to so-called "second curve"
      innovations in the delivery of care. Implementation of integrated care pathways
      (ICPs) may be one solution to imminent cost and access pressures facing
      orthopaedic patients in this era of health-care accountability and reform. ICPs
      can lower costs and the duration of hospital stay while facilitating better
      outcomes through enhanced interspecialty communication. As with any innovation at
      the crossroads of paradigm change, implementation of integrated care pathways for
      orthopaedics may elicit surgeons' concern on a variety of grounds and on levels
      ranging from casual questioning to vehement opposition. No single method is
      always effective in promoting cooperation and adoption, so a combination of
      strategies offers the best chance of success. With a special focus on total joint
      replacement, we consider general patterns of resistance to change, styles of
      conflict, and specific issues that may underlie orthopaedic surgeon resistance to
      implementation of integrated care pathways. Methods to facilitate and sustain
      orthopaedic surgeon engagement in implementation of such pathways are discussed. 

PMID- 23864184
TI  - Surveillance of conservatively treated rotator cuff tears is warranted.
      Commentary on an article by Stefan Moosmayer, MD, PhD, et al.: "The natural
      history of asymptomatic rotator cuff tears. a three-year follow-up of fifty
      cases".

PMID- 23864185
TI  - Prophylaxis against venous thromboembolism after arthroplasty: establishing value
      requires more than one perspective. Commentary on an article by John T.
      Schousboe, MD, PhD, and Gregory A. Brown, MD, PhD: "Cost-effectiveness of low
      molecular-weight heparin compared with aspirin for prophylaxis against venous
      thromboembolism after total joint arthroplasty".

PMID- 23864186
TI  - Is off-label use of BMP in pediatric spine surgery now a standard of care?
      Commentary on an article by Amit Jain, MD, et al.: "Factors associated with use
      of bone morphogenetic protein during pediatric spinal fusion surgery. an analysis
      of 4817 patients".

PMID- 23864187
TI  - Outcomes after operative fixation of complete articular patellar fractures:
      assessment of functional impairment.
AB  - BACKGROUND: Patellar fractures are debilitating injuries that compromise the knee
      extensor mechanism and are frequently associated with poor outcomes. The purpose
      of this study was to quantify the functional outcomes of operative treatment of
      patellar fractures. METHODS: Functional outcome data on thirty patients with an
      isolated unilateral patellar fracture were prospectively obtained at three, six,
      and twelve months postoperatively. RESULTS: All fractures healed. There were two
      complications (7%) related to the surgery (wound dehiscence and refracture), and
      eleven patients (37%) underwent removal of symptomatic implants. The tibial
      plateau-patella angle demonstrated patella baja in seventeen (57%) of the
      patients. Anterior knee pain during activities of daily living was experienced by
      twenty-four (80%) of the patients. Clinical improvement occurred over the first
      six months. However, functional impairment persisted at twelve months, with
      objective testing demonstrating that the knee extensor mechanism on the injured
      side had deficits in strength (-41%), power (-47%), and endurance (-34%) as
      compared with the uninjured side. CONCLUSIONS: Despite advances in surgical
      protocols and acceptable radiographic outcomes, functional impairment remains
      common after treatment of patellar fractures. Rehabilitation strategies following
      surgical stabilization of these injuries will be a fruitful area for future
      clinical research.

PMID- 23864188
TI  - Update on the state of outcome measurement in total elbow arthroplasty research:
      identifying a need for consensus.
AB  - BACKGROUND: There is little consensus for a standard set of metrics to express
      outcome after total elbow arthroplasty. In order to set the stage for future work
      toward a core set of measurement tools, our goal was to gather a complete view of
      the outcomes used in total elbow arthroplasty research, the concepts of their
      focus, and their quality as measures of the target concept. METHODS: We reviewed
      the outcome measures for total elbow arthroplasty presented in the literature
      from 2004 to 2011 in terms of the instruments used and their concepts of focus.
      We reviewed the reliability, validity, and responsiveness of the prevailing
      measurement tools. RESULTS: Of the seventy-two articles identified, 90% (sixty
      five) used elbow-specific aggregate outcome measures, which combine concepts,
      such as physiological variables, with symptom status and functional status. The
      Mayo Elbow Performance Score, or a variation of that scoring system, was used in
      fifty-four (75%) of the seventy-two articles. Most outcomes pertained to
      biological and physiological variables, with fewer outcomes focusing on symptoms,
      function, or overall health status. A review of the measurement properties of the
      elbow-specific aggregate outcome measures did not reveal one to be superior.
      CONCLUSIONS: Overall, total elbow arthroplasty outcomes are heterogeneous in
      their reporting and lack standardization. The total elbow arthroplasty literature
      relies on several physician-derived elbow-specific aggregate measures and focuses
      primarily on physiological variables. The relative merits of aggregating findings
      into a single scoring system versus as separate components should be explored
      further. Finally, consideration should be given to patient-reported outcome
      measures in total elbow arthroplasty research. CLINICAL RELEVANCE: This study of
      the current "state of practice" for outcome measurement in total elbow
      arthroplasty revealed gaps in the breadth of measurement and a lack of
      comparability in elbow scoring systems that could hinder our ability to clearly
      and fully understand outcome after total elbow arthroplasty. Future consensus
      work could address both concerns and assist in the development of a core set of
      outcome measures.

PMID- 23864189
TI  - Risk factors for thirty-day morbidity and mortality following knee arthroscopy: a
      review of 12,271 patients from the national surgical quality improvement program
      database.
AB  - BACKGROUND: Knee arthroscopy is among the most common orthopaedic surgical
      procedures. However, the incidence and risk factors for postsurgical morbidity
      and mortality remain poorly defined. METHODS: The American College of Surgeons
      National Surgical Quality Improvement Program prospectively collects thirty-day
      morbidity and mortality data from more than 258 hospitals around the United
      States. We used Current Procedural Terminology codes to retrospectively query the
      database and identified 12,271 cases of elective knee arthroscopy performed from
      January 1, 2005, to December 31, 2010. Postoperative complications were divided
      into categories of minor morbidity, major morbidity or mortality, or any
      complication. The potential risk factors for complications were analyzed with use
      of univariate and multivariate analyses. RESULTS: The overall incidence of any
      complication was 1.6% (199 patients). The major morbidity was 0.76% (ninety-three
      patients), which included one patient death (0.008%), and the minor morbidity was
      0.86% (106 patients). The most frequent major complication was a return to the
      operating room. The most common minor complication was deep venous thrombosis or
      thrombophlebitis. The risk factors identified in the univariate analysis for any
      complication included black race, prior operation within thirty days, American
      Society of Anesthesiologists class, and operative time of >1.5 hours as compared
      with <=1.5 hours (p < 0.05 for each). The independent risk factors identified in
      the multivariate analysis for any complication included black race (odds ratio,
      1.81 [95% confidence interval, 1.13 to 2.89]), prior operation within thirty days
      (odds ratio, 6.33 [95% confidence interval, 1.45 to 27.66]), operative time of
      >1.5 hours (odds ratio, 1.84 [95% confidence interval, 1.21 to 2.78]), and age of
      forty to sixty-five years (odds ratio, 1.46 [95% confidence interval, 1.01 to
      2.11]). CONCLUSIONS: The incidence of complication following elective knee
      arthroscopy is low. The data presented here should be useful for providing
      prognostic information to patients during informed consent. Surgeons should be
      encouraged to minimize operative time whenever possible, and may wish to delay
      elective arthroscopy in patients who have had other recent surgical procedures.

PMID- 23864190
TI  - MRI of the elbow: techniques and spectrum of disease: AAOS exhibit selection.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of the elbow allows for high
      resolution evaluation of osseous and soft-tissue structures, including ligaments,
      tendons, nerves, and muscles. Multiple imaging techniques and pulse sequences
      exist. The purpose of this article is to update orthopaedic surgeons on current
      MRI techniques and illustrate the spectrum of elbow pathology detectable by MRI.
      METHODS: We searched MEDLINE with use of the keywords "MRI" and "elbow" for
      studies less than five years old evaluating MRI techniques. These papers, our
      experience, and textbooks reviewing elbow MRI provided the information for this
      article. RESULTS: We discuss the essentials and applications of the following
      techniques: (1) conventional, non-gadolinium-enhanced MRI; (2) gadolinium
      enhanced MRI; and (3) magnetic resonance arthrography. The classic MRI
      appearances of occult fractures, loose bodies, ulnar collateral ligament
      injuries, lateral collateral ligament complex injuries, biceps tendon injuries,
      triceps tendon injuries, lateral epicondylitis, medial epicondylitis, septic
      arthritis, osteomyelitis, osteochondritis dissecans, compression neuropathies,
      synovial disorders, and various soft-tissue masses are reviewed. CONCLUSIONS: MRI
      is a valuable, noninvasive method of elbow evaluation. This article updates
      orthopaedic surgeons on the various available MRI techniques and facilitates
      recognition of the MRI appearances of the most commonly seen pathologic elbow
      conditions.

PMID- 23864191
TI  - Effects of ex vivo skin microbiopsy on histopathologic diagnosis in melanocytic
      skin lesions.

PMID- 23864193
TI  - Tocilizumab in amyloidosis-associated kidney disease secondary to inflammatory
      bowel diseases.

PMID- 23864192
TI  - Selective and efficient extraction of recombinant proteins from the periplasm of
      Escherichia coli using low concentrations of chemicals.
AB  - Experiments were conducted to determine chemicals at low concentrations, which
      can be utilized for selective release of periplasmic proteins. It was revealed
      that 80-100 % of the activity of alpha-amylase, beta-lactamase, and Fab D1.3 was
      retained in the presence of 0.05 and 0.1 % Triton X-100, 0.1 % Tween 20, 0.1 %
      DOC, 0.01 % BAC, 0.01 % CTAB, 10 mM EDTA, 1 mM and 10 mM DEA, 10 mM NTA, 0.1 and
      1 % SHMP, 200 mM urea, 100-500 mM GndCl, and 1 % solvents (hexane, xylene,
      toluene, benzene, pyridine and isoamyl alcohol). Performance of these chemicals,
      recognized as generally safe, for selective release of proteins from the
      periplasm of Escherichia coli was investigated. DOC was a general and very
      efficient agent, and at concentrations as low as 0.05, 0.1, and 0.025 %, released
      beta-lactamase, alpha-amylase, and Fab D1.3 selectively with yield factors of
      2.7, 2.3, and 3.6 times greater than osmotic shock procedure, respectively. EDTA
      (1 and 10 mM) discharged Fab D1.3 with efficiency more than osmotic shock (target
      protein yield of 110 and 138 %, correspondingly). Isoamyl alcohol (10 % v/v) was
      effective for periplasmic release of alpha-amylase and particularly Fab D1.3,
      with target protein yields of 75 and 168 %, respectively. 

PMID- 23864194
TI  - The differential effects of statins on the risk of developing pancreatic cancer:
      a case-control study in two centres in the United Kingdom.
AB  - INTRODUCTION: There are plausible biological mechanisms for how statins may
      prevent pancreatic cancer, although the evidence from epidemiological studies in
      the general population is conflicting. This study aims to clarify whether statins
      exert their effects in specific sub-groups, namely, gender, smoking status and
      diabetes. METHODS: A matched case-control study was conducted in patients
      diagnosed with pancreatic cancer, and a group of dermatology patients of similar
      ages and gender, diagnosed with basal cell carcinoma. Participants' medical
      records were reviewed for information on statin use prior to diagnosis. Odds
      ratios and 95 % CIs for the development of pancreatic cancer were estimated using
      conditional logistic regression. Subgroup analysis was performed in men, women,
      smokers and those with type 2 diabetes. RESULTS: Two hundred fifty-two cases
      (median age 71 years, range 48-73 years, 51 % women) and 504 controls were
      identified, of which 23 % of cases were regular statin users versus 21 % of
      controls. In the general study population there was no association between
      pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53-1.23, p = 0.33).
      However, in male smokers, regular statin use was associated with significantly
      reduced odds of pancreatic cancer compared to male smokers not prescribed a
      statin (OR 0.11, 95 % CI 0.01-0.96, p = 0.05). In patients with type 2 diabetes
      statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35-2.45, p =
      0.80), with no gender effects. CONCLUSIONS: In male smokers, statins may reduce
      the odds of pancreatic cancer. Statin use should be measured in aetiological
      studies of pancreatic cancer but analysed in specific sub-groups. Future work
      should investigate statins as chemopreventative agents in this high risk sub
      group.

PMID- 23864195
TI  - Knockdown of inhibitor of growth protein 2 inhibits cell invasion and enhances
      chemosensitivity to 5-FU in human gastric cancer cells.
AB  - BACKGROUND: The inhibitor of growth (ING) family is involved in multiple cellular
      functions, but the role of ING2 in gastric cancer progression is unclear. AIM: To
      investigate the effects of ING2 gene knockdown on chemosensitivity to 5
      fluorouracil (5-FU) in human gastric cancer cells and its possible mechanisms.
      METHODS: Short hairpin RNA (shRNA) targeting ING2 (shING2) was transfected into
      MGC-803 cells using Lipofectamine 2000, and stable transfection cell lines were
      established using G418. Cell viability, cell cycle distribution, cell apoptosis,
      and invasive ability were measured to determine the influence of ING2 knockdown
      on cell biologic characteristics. Messenger RNA (mRNA) and protein levels of
      ING2, cyclin D1, NF-kappaB/p65, and several matrix metalloproteinases (MMPs) were
      determined by use of real-time polymerase chain reaction (PCR) or Western
      blotting, respectively. RESULTS: Our results showed that ING2 knockdown induced
      cell apoptosis and inhibited cell viability significantly (P < 0.05).
      Additionally, ING2 knockdown induced a specific G0/G1 arrest. Furthermore, the
      suppression of ING2 could enhance the chemosensitivity of gastric cancer cells to
      5-FU significantly. Moreover, knockdown of ING2 expression significantly reduced
      cellular metastatic ability and expression of MMPs in MGC-803 cells. The
      expression of cyclin D1 and NF-kappaB/p65 was also markedly inhibited in MGC
      803/shING2 cells compared with control cells. CONCLUSIONS: ING2 not only plays an
      essential role in the growth and invasion of MGC-803 cells but also represents a
      potential approach to chemosensitization therapy in human gastric cancer.

PMID- 23864196
TI  - Using small-for-size grafts in living donor liver transplantation recipients with
      high MELD scores should not be considered a contraindication.

PMID- 23864198
TI  - beta-Nerve growth factor attenuates hepatocyte injury induced by D-galactosamine
      in vitro via TrkA NGFR.
AB  - Nerve growth factor (NGF) regulates the proliferation, differentiation and
      survival of cells and is also involved in the wound healing and tissue remodeling
      processes. The biological effects of NGF are dependent upon receptor signal
      mediating functions, which differ between cells. This study attempted to
      investigate the hepatoprotective effect and possible mechanism of beta-NGF on D
      galactosamine (D-GalN)-injured human liver L-02 cell lines. We demonstrated that
      L-02 cells expressed the neurotrophin receptors tyrosine kinase-A nerve growth
      factor receptor (TrkA NGFR) and p75 pan-neurotrophin receptor (p75NTR).
      Recombinant human beta-NGF markedly reduced cell injury and promoted the
      proliferation of L-02 cells damaged by D-GalN. However, this proliferation effect
      was blocked by the anti-TrkA NGFR antibody. Lactate dehydrogenase (LDH) and
      malondialdehyde (MDA) were released at reduced levels in the L-02 cell culture
      supernatant pretreated with beta-NGF. Furthermore, the albumin (ALB) content in
      the cell medium and intracellular glutathione (GSH) levels were markedly
      augmented, and the permeability of the mitochondrial membrane of the L-02 cells
      was improved by beta-NGF. Our results suggested that exogenous beta-NGF protects
      L-02 cells from D-GalN-induced injury through the NGF/TrkA NGFR signaling
      pathway.

PMID- 23864197
TI  - Nucleolar dominance and different genome behaviors in hybrids and allopolyploids.
AB  - Many plants are allopolyploids with different nuclear genomes from two or more
      progenitors, but cytoplasmic genomes typically inherited from the female parent.
      The importance of this speciation mechanism has stimulated the extensive
      investigations of genetic consequences of genome mergers in several experimental
      systems during last 20 years. The dynamic nature of polyploid genomes is
      recognized, and widespread changes to gene expression are revealed by
      transcriptomic analysis. These progresses show different stabilities of parental
      genomes and their unequal contributions to the transcriptome, proteome, and
      phenotype. We review the results in systems where extensive genetic analyses have
      been conducted and propose possible mechanisms for biased behavior of parental
      genomes in allopolyploids, including the role of nucleolar dominance. It is
      hypothesized that the novel ribosomes with rRNAs from uniparental genome and the
      ribosomal proteins of biparental origins have some impacts on the biased cellular
      and genetic behaviors of parental genomes in hybrids and allopolyploids. 

PMID- 23864199
TI  - Trends, risk factors and mortality among women with venous thromboembolism during
      labour and delivery: a population-based study of 8 million births.
AB  - OBJECTIVE: Venous thromboembolism (VTE) is amongst the main causes of maternal
      death in the developed world. The objective of this study is to elucidate risk
      factors of VTE and specifically, predictors of fatal thromboembolic disease
      during the delivery. STUDY DESIGN: We conducted a population-based cohort study
      on 8 million birth records using the Healthcare Cost and Utilisation Project
      Nationwide Inpatient Sample from 1999 to 2008 to estimate the incidence and case
      fatality of VTE's during labour admission. Logistic regression was used to
      calculate the odds ratio (OR) and corresponding 95 % confidence intervals (CIs)
      of demographic and obstetrical determinants of VTEs and fatal VTEs. RESULTS: The
      overall incidence of VTE was 167.7/100,000 births, increasing over the 10-year
      period, with an average case fatality rate of 0.41 %. VTE was associated with
      maternal age above 25, elderly primigravida, multigravida, black race, smoking,
      thrombophilia, cardiovascular disease, hypertension, obesity, postpartum
      haemorrhage and blood transfusion. Predictors of VTE fatalities included black
      race, hypertension, caesarean section and transfusion. CONCLUSION: VTE is a rare
      but serious condition that is increasing in incidence and is associated with a
      significant degree of maternal morbidity and mortality. Further research
      targeting prevention among high-risk groups is warranted.

PMID- 23864200
TI  - Blastocyst formation, pregnancy and birth (more than 10 years after the birth of
      the first child from the same IVF cycle), derived from human PN-stage
      cryopreserved for 10 years.

PMID- 23864201
TI  - Does ambient air pollutants increase the risk of fetal loss? A case-control
      study.
AB  - OBJECTIVE: To examine the associations between the ambient air pollution and
      early fetal loss. STUDY DESIGN: A retrospective case-control study was conducted.
      959 fetal losses and 959 normal intrauterine pregnancies within 14 weeks of
      pregnancy in 15 general or obstetrics and gynecology hospitals were selected into
      case and control groups, respectively. Data based on hospital records and
      national pollution monitor station records were collected. Logistic regression
      model was conducted to examine the associations between 4 ambient air pollutants
      (SO2, PM10, NO2 and TSP) exposures and fetal loss. RESULTS: The ratio of fetal
      loss to termination of pregnancy for heating months (2.28 %) was significantly (P
      < 0.001) higher than that for the non-heating months (1.77 %). Logistic
      regression suggested that fetal loss within 14 weeks was associated with higher
      exposure to SO2 (OR = 19.76, 95 % CI 2.34-166.71) and TSP (OR = 2.04, 95 % CI
      1.01-4.13) in the first month of pregnancy. CONCLUSION: Exposure to high levels
      of SO2 and TSP during the first month of pregnancy was associated with an
      increased risk of fetal loss in early pregnancy.

PMID- 23864202
TI  - Measure DRAM with a purpose: diagnose or evaluate.

PMID- 23864203
TI  - Image classification via object-aware holistic superpixel selection.
AB  - In this paper, we propose an object-aware holistic superpixel selection (HPS)
      method to automatically select the discriminative superpixels of an image for
      image classification purpose. Through only considering the selected superpixels,
      the interference of cluttered background on the object can be alleviated
      effectively and thus the classification performance is significantly enhanced. In
      particular, for an image, HPS first selects the discriminative superpixels for
      the characteristics of certain class, which can together match the object
      template of this class well. In addition, these superpixels compose a class
      specific matching region. Through performing such superpixel selection for
      several most probable classes, respectively, HPS generates multiple class
      specific matching regions for a single image. Then, HPS merges these matching
      regions into an integral object region through exploiting their pixel-level
      intersection information. Finally, such object region instead of the original
      image is used for image classification. An appealing advantage of HPS is the
      ability to alleviate the interference of cluttered background yet not require the
      object to be segmented out accurately. We evaluate the proposed HPS on four
      challenging image classification benchmark datasets: Oxford-IIIT PET 37, Caltech
      UCSD Birds 200, Caltech 101, and PASCAL VOC 2011. The experimental results
      consistently show that the proposed HPS can remarkably improve the classification
      performance. 

PMID- 23864204
TI  - Self-similar anisotropic texture analysis: the hyperbolic wavelet transform
      contribution.
AB  - Textures in images can often be well modeled using self-similar processes while
      they may simultaneously display anisotropy. The present contribution thus aims at
      studying jointly selfsimilarity and anisotropy by focusing on a specific
      classical class of Gaussian anisotropic selfsimilar processes. It will be first
      shown that accurate joint estimates of the anisotropy and selfsimilarity
      parameters are performed by replacing the standard 2D-discrete wavelet transform
      with the hyperbolic wavelet transform, which permits the use of different
      dilation factors along the horizontal and vertical axes. Defining anisotropy
      requires a reference direction that needs not a priori match the horizontal and
      vertical axes according to which the images are digitized; this discrepancy
      defines a rotation angle. Second, we show that this rotation angle can be jointly
      estimated. Third, a nonparametric bootstrap based procedure is described, which
      provides confidence intervals in addition to the estimates themselves and enables
      us to construct an isotropy test procedure, which can be applied to a single
      texture image. Fourth, the robustness and versatility of the proposed analysis
      are illustrated by being applied to a large variety of different isotropic and
      anisotropic self-similar fields. As an illustration, we show that a true
      anisotropy built-in self-similarity can be disentangled from an isotropic self
      similarity to which an anisotropic trend has been superimposed. 

PMID- 23864205
TI  - PET protection optimization for streaming scalable videos with multiple
      transmissions.
AB  - This paper investigates priority encoding transmission (PET) protection for
      streaming scalably compressed video streams over erasure channels, for the
      scenarios where a small number of retransmissions are allowed. In principle, the
      optimal protection depends not only on the importance of each stream element, but
      also on the expected channel behavior. By formulating a collection of hypotheses
      concerning its own behavior in future transmissions, limited-retransmission PET
      (LR-PET) effectively constructs channel codes spanning multiple transmission
      slots and thus offers better protection efficiency than the original PET. As the
      number of transmission opportunities increases, the optimization for LR-PET
      becomes very challenging because the number of hypothetical retransmission paths
      increases exponentially. As a key contribution, this paper develops a method to
      derive the effective recovery-probability versus redundancy-rate characteristic
      for the LR-PET procedure with any number of transmission opportunities. This
      significantly accelerates the protection assignment procedure in the original LR
      PET with only two transmissions, and also makes a quick and optimal protection
      assignment feasible for scenarios where more transmissions are possible. This
      paper also gives a concrete proof to the redundancy embedding property of the
      channel codes formed by LR-PET, which allows for a decoupled optimization for
      sequentially dependent source elements with convex utility-length characteristic.
      This essentially justifies the source-independent construction of the protection
      convex hull for LR-PET. 

PMID- 23864206
TI  - Enhancement of backlight-scaled images.
AB  - Switching the liquid crystal display (LCD) backlight of a portable multimedia
      device to a low power level saves energy but results in poor image quality
      especially for the low-luminance image areas. In this paper, we propose an image
      enhancement algorithm that overcomes such effects of dim LCD backlight by taking
      the human visual property into consideration. It boosts the luminance of image
      areas below the perceptual threshold while preserving the contrast of the other
      image areas. We apply the just noticeable difference theory and decompose an
      image into an HVS response layer and a background luminance layer. The boosting
      and compression processes, which enhance the visibility of the low-luminance
      image areas, are carried out in the background luminance layer to avoid luminance
      gradient reversal and over-compensation. The contrast of the processed image is
      further enhanced by exploiting the Craik-O'Brein-Cornsweet visual illusion.
      Experimental results are provided to show the performance of the proposed
      algorithm.

PMID- 23864207
TI  - Youth participation in organized and informal sports activities across childhood
      and adolescence: exploring the relationships of motivational beliefs,
      developmental stage and gender.
AB  - Involvement in physically active pursuits, such as sports, contributes to
      achieving and maintaining good emotional and physical health. The central goal of
      this article was to examine the longitudinal relationships between participation
      (i.e., time spent in the activities) in organized and informal sports contexts
      and motivational beliefs, and factors that might impact these relationships, such
      as developmental stage and gender. The data for the current study were drawn from
      the childhood and beyond longitudinal study, which utilized a cohort sequential
      design with data collected on three cohorts across four waves. The current study
      sample included 986 European American youth (51 % female), who t were mostly from
      working- and middle-class families. Self-report questionnaires were used to
      collect data from the youth about their participation in sports and their
      motivational beliefs (i.e., value and perceptions of competence) about this
      activity. Structural equation modeling was used to examine the relationships
      between participation and motivational beliefs across childhood and adolescence.
      The results provide some support for a model of reciprocal relationships between
      participation and motivational beliefs in organized and informal sports
      activities. These relationships between participation and motivational beliefs
      did not vary significantly based on developmental stage or by gender. Overall,
      the findings suggest that participation in organized and informal sports contexts
      may be fostered by supporting the development of positive motivational beliefs
      about the activities across developmental periods. 

PMID- 23864208
TI  - Drugs, muscle pallor, and pyomyositis.
AB  - A 33-year-old athletic male was unexpectedly found dead in his bed. For several
      days prior to his death he complained of tenderness and swelling of his right
      buttock. The post-mortem examination revealed unilateral pale gluteal muscles and
      pustular impetiginized skin lesions of the right lower leg. The muscle histology
      demonstrated pronounced acute inflammation and limited necrosis of muscle fibers
      confined to the right gluteal muscles. Vascular occlusion and renal abnormalities
      were excluded by post-mortem angiography and histology respectively, and the
      diagnosis of non-tropical pyomyositis, possibly originating from the
      dermatological infection, was made. Toxicological testing revealed a potentially
      lethal intoxication with fentanyl and morphine. Pyomyositis is etiologically
      attributed to an infection and predominantly affects large limb or trunk muscles.
      Males are affected more frequently than females. Histologically, it is dominated
      by acute inflammatory infiltrates and may lead to sepsis and subsequent death.
      Although occurring less frequently, pyomyositis must be considered in the
      differential diagnosis of macroscopic localized muscle pallor, together with
      vascular occlusion and rhabdomyolysis. In such cases, only the examination of
      fresh frozen muscle tissue samples from different locations, together with the
      histological examination of the internal organs, particularly the kidneys, will
      facilitate the confirmation of the correct diagnosis. 

PMID- 23864209
TI  - How do patients with end-stage ankle arthritis decide between two surgical
      treatments? A qualitative study.
AB  - OBJECTIVE: To examine how patients decide between ankle fusion and ankle
      replacement in end-stage ankle arthritis. DESIGN: Purposive patient selection,
      semistructured interviews, thematic analysis. SETTING: Royal National Orthopaedic
      Hospital, Stanmore, UK. PARTICIPANTS: 14 patients diagnosed with end-stage ankle
      osteoarthritis. RESULTS: We interviewed 6 men and 8 women with a mean age of 58
      years (range 41-83). All had opted for surgery after failure of at least 6 months
      of conservative management, sequentially trading-off daily activities to limit
      the evolving pain. To decide between two offered treatments of ankle fusion and
      total ankle replacement (TAR), three major sources informed the patients'
      decision-making process: their surgeon, peers and the internet. The treating
      surgeon was viewed as the most reliable and influential source of information.
      Information gleaned from other patients was also important, but with questionable
      reliability, as was information from the internet, both of which invariably
      required validation by the surgeon and in some cases the general practitioner.
      CONCLUSIONS: Patients seek knowledge from a wealth of sources including the
      internet, web forums and other patients. While they leverage each of these
      sources to guide decision-making, the most important and influential factor in
      governing how patients decide on any particular surgical intervention is their
      surgeon. A high quality doctor-patient relationship, coupled with clear, balanced
      and complete information is essential to enable shared decision-making to become
      a standard model of care.

PMID- 23864210
TI  - Prospective registration, bias risk and outcome-reporting bias in randomised
      clinical trials of traditional Chinese medicine: an empirical methodological
      study.
AB  - BACKGROUND: Clinical trials on Traditional Chinese Medicine (TCM) should be
      registered in a publicly accessible international trial register and report on
      all outcomes. We systematically assessed and evaluated TCM trials in registries
      with their subsequent publications. OBJECTIVE: To describe the characteristics of
      TCM trials, estimate bias risk and outcome-reporting bias in clinical trials.
      DATA SOURCES AND STUDY SELECTION: Fifteen trial registries were searched from
      their inception to July 2012 to identify randomised trials on TCM including
      Chinese herbs, acupuncture and/or moxibustion, cupping, tuina, qigong, etc. DATA
      EXTRACTION: We extracted data including TCM specialty and treated
      disease/conditions from the registries and searched for subsequent publications
      in PubMed and Chinese databases. We compared information in the registries of
      completed trials with any publications focusing on study design, sample size,
      randomisation, bias risk including reporting bias from the register protocol.
      RESULTS: 1096 registered randomised trials were identified evaluating TCM, of
      which 505 were completed studies (46.1%). The most frequent conditions were pain
      (13.3%), musculoskeletal (11.7%), nervous (8.7%), digestive (7.1%), circulatory
      (6.5%), respiratory (6.3%), mental and behavioural disorders (6.2%) and cancer
      (6.0%). The trial register data identified parallel, phase II/III randomised
      trials with sample size estimations and blinding, but limited information about
      randomisation (sequence generation and allocation concealment). Comparing trial
      registration data of 115 completed trials (22.8%) with their subsequent 136
      publications, inconsistencies were identified in one or more of the following:
      sample size (11%), outcome assessor blinding (37.5%), primary outcomes (29%) and
      safety (28%) reporting. CONCLUSIONS: Increasing numbers of clinical trials
      investigating a variety of TCM interventions have been registered in
      international trial registries. The study design of registered TCM trials has
      improved in estimating sample size, use of blinding and placebos. However,
      selective outcome reporting is widespread and similar to conventional medicine
      and therefore study conclusions should be interpreted with caution.

PMID- 23864211
TI  - Impact of clinical trial findings on Bell's palsy management in general practice
      in the UK 2001-2012: interrupted time series regression analysis.
AB  - OBJECTIVES: To measure the incidence of Bell's palsy and determine the impact of
      clinical trial findings on Bell's palsy management in the UK. DESIGN: Interrupted
      time series regression analysis and incidence measures. SETTING: General
      practices in the UK contributing to the Clinical Practice Research Datalink
      (CPRD). PARTICIPANTS: Patients >=16 years with a diagnosis of Bell's palsy
      between 2001 and 2012. INTERVENTIONS: (1) Publication of the 2004 Cochrane
      reviews of clinical trials on corticosteroids and antivirals for Bell's palsy,
      which made no clear recommendation on their use and (2) publication of the 2007
      Scottish Bell's Palsy Study (SBPS), which made a clear recommendation that
      treatment with prednisolone alone improves chances for complete recovery. MAIN
      OUTCOME MEASURES: Incidence of Bell's palsy per 100 000 person-years. Changes in
      the management of Bell's palsy with either prednisolone therapy, antiviral
      therapy, combination therapy (prednisolone with antiviral therapy) or untreated
      cases. RESULTS: During the 12-year period, 14 460 cases of Bell's palsy were
      identified with an overall incidence of 37.7/100 000 person-years. The 2004
      Cochrane reviews were associated with immediate falls in prednisolone therapy (
      6.3% (-11.0 to -1.6)), rising trends in combination therapy (1.1% per quarter
      (0.5 to 1.7)) and falling trends for untreated cases (-0.8% per quarter (-1.4 to 
      0.3)). SBPS was associated with immediate increases in prednisolone therapy (5.1%
      (0.9 to 9.3)) and rising trends in prednisolone therapy (0.7% per quarter (0.4 to
      1.2)); falling trends in combination therapy (-1.7% per quarter (-2.2 to -1.3));
      and rising trends for untreated cases (1.2% per quarter (0.8 to 1.6)). Despite
      improvements, 44% still remain untreated. CONCLUSIONS: SBPS was clearly
      associated with change in management, but a significant proportion of patients
      failed to receive effective treatment, which cannot be fully explained. Clarity
      and uncertainty in clinical trial recommendations may change clinical practice.
      However, better ways are needed to understand and circumvent barriers in
      implementing clinical trial findings.

PMID- 23864212
TI  - Effects of enzyme replacement therapy for cardiac-type Fabry patients with a
      Chinese hotspot late-onset Fabry mutation (IVS4+919G>A).
AB  - OBJECTIVE: Current studies of newborn screening for Fabry disease in Taiwan have
      revealed a remarkably high prevalence of cardiac-type Fabry disease with a
      Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). DESIGN: Retrospective
      cohort study. SETTING: Tertiary medical centre. PARTICIPANTS: 21 patients with
      cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with
      classic Fabry disease (4 men and 11 women) treated with biweekly intravenous
      infusions of agalsidase beta (1 mg/kg) or agalsidase alpha (0.2 mg/kg) for at
      least 6 months. OUTCOME MEASURES: These data were collected at the time before
      enzyme replacement therapy (ERT) began and followed up after ERT for at least 6
      months, including patient demographics, medical history, parameter changes of
      cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3)
      and Mainz Severity Score Index. RESULTS: After 6-39 months of ERT, plasma lyso
      Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with
      cardiac-type and classic Fabry disease, respectively, which indicated an
      improvement of disease severity. For patients with cardiac-type Fabry disease,
      echocardiography revealed the reduction or stabilisation of left ventricular mass
      index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior
      wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively,
      as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type.
      Most patients showed stable renal function after ERT. There were statistically
      significant improvements (p<0.05) between the data at baseline and those after
      ERT for values of plasma lyso-Gb3, LVMI, IVS, LPW and Mainz Severity Score Index.
      No severe clinical events were reported during the treatment. CONCLUSIONS: ERT is
      beneficial and appears to be safe for Taiwanese patients with cardiac-type Fabry
      disease, as well as for those with the classic type.

PMID- 23864213
TI  - Characteristics of 5-year-olds who catch-up with MMR: findings from the UK
      Millennium Cohort Study.
AB  - OBJECTIVES: To examine predictors of partial and full measles, mumps and rubella
      (MMR) vaccination catch-up between 3 and 5 years. DESIGN: Secondary data analysis
      of the nationally representative Millennium Cohort Study (MCS). SETTING: Children
      born in the UK, 2000-2002. PARTICIPANTS: 751 MCS children who were unimmunised
      against MMR at age 3, with immunisation information at age 5. MAIN OUTCOME
      MEASURES: Catch-up status: unimmunised (received no MMR), partial catch-up
      (received one MMR) or full catch-up (received two MMRs). RESULTS: At age 5, 60.3%
      (n=440) children remained unvaccinated, 16.1% (n=127) had partially and 23.6%
      (n=184) had fully caught-up. Children from families who did not speak English at
      home were five times as likely to partially catch-up than children living in
      homes where only English was spoken (risk ratio 4.68 (95% CI 3.63 to 6.03)). Full
      catch-up was also significantly more likely in those did not speak English at
      home (adjusted risk ratio 1.90 (1.08 to 3.32)). In addition, those from
      Pakistan/Bangladesh (2.40 (1.38 to 4.18)) or 'other' ethnicities (such as
      Chinese) (1.88 (1.08 to 3.29)) were more likely to fully catch-up than White
      British. Those living in socially rented (1.86 (1.34 to 2.56)) or 'Other' (2.52
      (1.23 to 5.18)) accommodations were more likely to fully catch-up than home
      owners, and families were more likely to catch-up if they lived outside London
      (1.95 (1.32 to 2.89)). Full catch-up was less likely if parents reported medical
      reasons (0.43 (0.25 to 0.74)), a conscious decision (0.33 (0.23 to 0.48)), or
      'other' reasons (0.46 (0.29 to 0.73)) for not immunising at age 3 (compared with
      'practical' reasons). CONCLUSIONS: Parents who partially or fully catch-up with
      MMR experience practical barriers and tend to come from disadvantaged or ethnic
      minority groups. Families who continue to reject MMR tend to have more advantaged
      backgrounds and make a conscious decision to not immunise early on. Health
      professionals should consider these findings in light of the characteristics of
      their local populations.

PMID- 23864214
TI  - A school-based education programme to reduce salt intake in children and their
      families (School-EduSalt): protocol of a cluster randomised controlled trial.
AB  - INTRODUCTION: The current salt intake is very high for children as well as adults
      in China. A reduction in salt intake is one of the most cost-effective measures
      to curb the rapidly growing disease burden attributed to blood pressure and
      cardiovascular disease in the Chinese population. A lower salt diet starting from
      childhood has the potential to prevent the development of such conditions. The
      School-EduSalt (School-based Education Programme to Reduce Salt) study aims to
      determine whether an education programme targeted at school children can lower
      salt intake in children and their families. METHODS AND ANALYSIS: The study is
      designed as a cluster randomised controlled trial. The location is Changzhi,
      Shanxi province in northern China. The study population will consist of 28
      primary schools with 280 children aged ~11 years and 560 adult family members.
      Children in the intervention group will be educated on how to reduce salt intake.
      They will then be empowered to deliver the salt reduction message home to their
      families. In particular, children need to persuade the person who does the
      cooking to reduce the amount of salt used during food preparations. The duration
      of the intervention is one school term (~4.5 months). The primary outcome is the
      difference between the intervention and the control group in the change in 24 h
      urinary sodium and the secondary outcome is the difference between the
      intervention and control group in the change of blood pressure. An economic
      evaluation will be undertaken to assess cost-effectiveness. ETHICS AND
      DISSEMINATION: The study has been approved by The Queen Mary Research Ethics
      Committee (QMREC2012/81) and Peking University Health Science Centre IRB
      (IRB00001052-12072). Study findings will be disseminated widely through
      conference presentations and peer-reviewed publications. PROTOCOL REGISTRATION:
      Protocol Registered on ClinicalTrials.gov NCT01821144.

PMID- 23864215
TI  - Editorial comment: Lessons learned with tricuspid valve replacement.

PMID- 23864216
TI  - Clinical outcomes through 12 months in patients with degenerative mitral
      regurgitation treated with the MitraClip(r) device in the ACCESS-EUrope Phase I
      trial.
AB  - OBJECTIVES: Percutaneous treatment with the MitraClip device represents an
      alternative option for selected patients with degenerative mitral regurgitation
      (DMR) considered ineligible for surgery due to contraindications or high surgical
      risk by an inter-disciplinary heart team. We describe 12-month outcomes following
      treatment with the MitraClip device in DMR patients. METHODS: The MitraClip
      Therapy Economic and Clinical Outcomes Study Europe (ACCESS-EU) Study has
      completed the enrolment of 567 patients as of April 2011, 117 of whom were DMR.
      Baseline demographics, procedural and acute safety results at 30 days and
      survival at 12 months were evaluated in the DMR subset. Effectiveness results,
      defined by a reduction in MR, and improvement in clinical outcomes based on
      changes in New York Heart Association (NYHA) functional Class, 6-min walk test
      (6MWT) and quality-of-life data were also assessed. Furthermore, DMR patients
      were stratified into high- and low-risk subgroups (logistic European System of
      Cardiac Operative Risk Evaluation I (logEuroSCORE I >=20% or <20%, respectively)
      and differentially evaluated. RESULTS: One hundred and seventeen DMR patients
      underwent the MitraClip procedure with a 94.9% rate (111 of 117) of successful
      clip implantation. Baseline characteristics and comorbidities included NYHA Class
      III/IV (74%), left ventricular ejection fraction (LVEF) <40% (9%), prior cardiac
      surgery (24%) and prior myocardial infarction (MI) (22%). Mean logEuroSCORE I was
      15.5 +/- 13.3%. Mortalities at 30 days and 12 months were 6.0 and 17.1%,
      respectively. At 12 months, 74.6% (53 of 71) of patients in follow-up achieved MR
      <=grade 2+ and 80.8% (63 of 78) were in NYHA functional class I/II. Both
      Minnesota Living with Heart Failure questionnaire (MLHFQ) scores and 6MWT
      distance improved significantly at 12 months compared with baseline (P = 0.03 and
      P < 0.0001, respectively). CONCLUSIONS: The MitraClip procedure resulted in
      significant reductions in MR and improvements in clinical outcomes at 12 months
      in selected patients with severe DMR. MitraClip therapy may serve as a
      complementary non-surgical therapeutic option for DMR patients who are considered
      at high risk or ineligible for surgery by an inter-disciplinary dedicated heart
      team. Interventional treatment should be indicated following the discussion of
      patients in an inter-disciplinary conference of cardiologists and cardiac
      surgeons as suggested by current international guidelines.

PMID- 23864217
TI  - Re-repair of the mitral valve as a primary strategy for early and late failures
      of mitral valve repair.
AB  - OBJECTIVES: With the expanding uptake of mitral valve repair as the primary
      therapy for mitral valve regurgitation, an increasing cohort of patients are
      presenting with failures following valve repair. These patients have
      traditionally been treated by mitral valve replacement. We have adopted an
      aggressive strategy of valve re-repair for failures of mitral valve repair and
      present our mid-term results. METHODS: Fifty-three consecutive adults underwent
      reoperation by a single surgical team for failed non-rheumatic mitral valve
      repair. Primary valve repair had been done for degenerative (n=38), congenital
      (n=6), infective (n=3), functional (n=1) or unknown (n=5) mitral disease. The
      reoperative mitral procedure occurred at a median interval of 3 (interquartile
      range 0.9-6.5) years from the primary mitral valve repair. Valve re-repair was
      attempted if the anterior leaflet was sufficiently pliable, and lesions causing
      recurrence were identifiable and deemed treatable. Standard repair techniques
      were employed in re-repair procedures. RESULTS: Valve analysis showed that the
      mode of failure was progression of original disease in 19 (36%), technical
      failure in 20 (38%) and new disease in 14 (26%) patients. Valve re-repair was
      successfully accomplished in 45 (85%) patients. Re-repair was most frequent when
      the prior aetiology was degenerative (34 of 38, 90%) as opposed to non
      degenerative (11 of 15, 73%). There were no hospital deaths. Four-year patient
      survival was 97%. Freedoms from moderate mitral regurgitation were 100, 95, 88
      and 80% at discharge and at 1, 3, and 4 years, respectively. There were no
      reoperations in the follow-up period. CONCLUSIONS: Re-repair of the mitral valve
      is feasible in most of the cases of failed mitral valve repair of non-rheumatic
      aetiology and has acceptable mid-term outcomes. The relatively high prevalence of
      technical failures as the mechanism of failure of the primary mitral valve repair
      suggests the need for ongoing surgical education and continuing development and
      refinement of repair techniques.

PMID- 23864218
TI  - Impacts of biotic resource enrichment on a predator-prey population.
AB  - The environmental carrying capacity is usually assumed to be fixed quantity in
      the classical predator-prey population growth models. However, this assumption is
      not realistic as the environment generally varies with time. In a bid for greater
      realism, functional forms of carrying capacities have been widely applied to
      describe varying environments. Modelling carrying capacity as a state variable
      serves as another approach to capture the dynamical behavior between population
      and its environment. The proposed modified predator-prey model is based on the
      ratio-dependent models that have been utilized in the study of food chains. Using
      a simple non-linear system, the proposed model can be linked to an intra-guild
      predation model in which predator and prey share the same resource. Distinct from
      other models, we formulate the carrying capacity proportional to a biotic
      resource and both predator and prey species can directly alter the amount of
      resource available by interacting with it. Bifurcation and numerical analyses are
      presented to illustrate the system's dynamical behavior. Taking the enrichment
      parameter of the resource as the bifurcation parameter, a Hopf bifurcation is
      found for some parameter ranges, which generate solutions that posses limit cycle
      behavior. 

PMID- 23864219
TI  - Reconstruction of certain phylogenetic networks from their tree-average
      distances.
AB  - Trees are commonly utilized to describe the evolutionary history of a collection
      of biological species, in which case the trees are called phylogenetic trees.
      Often these are reconstructed from data by making use of distances between extant
      species corresponding to the leaves of the tree. Because of increased recognition
      of the possibility of hybridization events, more attention is being given to the
      use of phylogenetic networks that are not necessarily trees. This paper describes
      the reconstruction of certain such networks from the tree-average distances
      between the leaves. For a certain class of phylogenetic networks, a polynomial
      time method is presented to reconstruct the network from the tree-average
      distances. The method is proved to work if there is a single reticulation cycle. 

PMID- 23864220
TI  - MisPred: a resource for identification of erroneous protein sequences in public
      databases.
AB  - Correct prediction of the structure of protein-coding genes of higher eukaryotes
      is still a difficult task; therefore, public databases are heavily contaminated
      with mispredicted sequences. The high rate of misprediction has serious
      consequences because it significantly affects the conclusions that may be drawn
      from genome-scale sequence analyses of eukaryotic genomes. Here we present the
      MisPred database and computational pipeline that provide efficient means for the
      identification of erroneous sequences in public databases. The MisPred database
      contains a collection of abnormal, incomplete and mispredicted protein sequences
      from 19 metazoan species identified as erroneous by MisPred quality control tools
      in the UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, NCBI/RefSeq and EnsEMBL databases.
      Major releases of the database are automatically generated and updated regularly.
      The database (http://www.mispred.com) is easily accessible through a simple web
      interface coupled to a powerful query engine and a standard web service. The
      content is completely or partially downloadable in a variety of formats. DATABASE
      URL: http://www.mispred.com.

PMID- 23864221
TI  - Assessing thalamocortical functional connectivity with Granger causality.
AB  - Assessment of network connectivity across multiple brain regions is critical to
      understanding the mechanisms underlying various neurological disorders.
      Conventional methods for assessing dynamic interactions include cross-correlation
      and coherence analysis. However, these methods do not reveal the direction of
      information flow, which is important for studying the highly directional
      neurological system. Granger causality (GC) analysis can characterize the
      directional influences between two systems. We tested GC analysis for its
      capability to capture directional interactions within both simulated and in vivo
      neural networks. The simulated networks consisted of Hindmarsh-Rose neurons; GC
      analysis was used to estimate the causal influences between two model networks.
      Our analysis successfully detected asymmetrical interactions between these
      networks ( , t -test). Next, we characterized the relationship between the
      "electrical synaptic strength" in the model networks and interactions estimated
      by GC analysis. We demonstrated the novel application of GC to monitor
      interactions between thalamic and cortical neurons following ischemia induced
      brain injury in a rat model of cardiac arrest (CA). We observed that during the
      post-CA acute period the GC interactions from the thalamus to the cortex were
      consistently higher than those from the cortex to the thalamus ( 1.983+/-0.278
      times higher, p = 0.021). In addition, the dynamics of GC interactions between
      the thalamus and the cortex were frequency dependent. Our study demonstrated the
      feasibility of GC to monitor the dynamics of thalamocortical interactions after a
      global nervous system injury such as CA-induced ischemia, and offers preferred
      alternative applications in characterizing other inter-regional interactions in
      an injured brain. 

PMID- 23864222
TI  - Atorvastatin safety in Kawasaki disease patients with coronary artery aneurysms.
AB  - Statins (HMG-CoA reductase inhibitors) may decrease inflammation in postacute
      Kawasaki disease (KD) complicated by coronary artery aneurysm (CAA) and promote
      vascular remodeling. There are limited data on their safety in young children.
      Twenty patients with CAAs after KD (median CAA z-score = +25) were treated with
      5/10 mg atorvastatin daily for a median of 2.5 years (range 0.5-6.8) starting at
      a median of 2.3 years (range 0.3-8.9) after acute KD (median age 9.3 years [range
      0.7-14.3]). Compliance with treatment was excellent: only one patient reported
      minor side effects (joint pain, no change in medication). Average total
      cholesterol before atorvastatin was 3.73 +/- 0.84 mmol/L and after atorvastatin
      was 3.21 +/- 0.46 mmol/L (relative decrease -14 %, p = 0.02); low-density
      lipoprotein cholesterol was 1.99 +/- 0.76 mmol/L before and only 1.49 +/- 0.27
      mmol/L after (relative decrease -20 %, p = 0.04); high-density lipoprotein was
      1.39 +/- 0.36 mmol/L before and 1.30 +/- 0.27 mmol/L after (relative decrease -4
      %, p = 0.35); and triglycerides were 0.71 +/- 0.28 mmol/L before and 0.71 +/-
      0.18 mmol/L after (relative decrease -5 %, p = 0.38). Nine of 20 patients (45 %)
      experienced at least 1 episode of hypocholesterolemia (total cholesterol <3.1
      mmol/L), and 2 patients required atorvastatin dose lowering. Transient mild
      increase of liver enzymes (aspartate aminotransferase/alanine aminotransferase 45
      60 U/L) were seen in 7 of 20 (35 %) patients with no patients experiencing more
      severe increases. Only one patient experienced increased creatine phosphokinase
      levels (>500 U/L). Serial measurements of age- and sex-specific percentiles of
      weight (estimated change: 1.4 [2.7] % per year, p = 0.60), height (estimated
      change: -3.2 [3.2] % per year, p = 0.32), and body mass index (estimated change:
      1.0 [2.9] % per year, p = 0.73) showed no association between anthropomorphic
      growth and atorvastatin treatment. Atorvastatin use in very young children with
      KD is safe but should be closely monitored. 

PMID- 23864223
TI  - Severe constrictive pericarditis after parvovirus B19 and human herpes virus 6
      infection in a 9-year-old girl.
AB  - We report on a 9-year-old girl who developed signs of congestive heart failure
      with significant ascites due to constrictive pericarditis. Cardiac
      catheterization was performed to establish the diagnosis and to rule out
      restrictive cardiomyopathy. Endomyocardial biopsies were positive for activated
      macrophages and small-vessel disease, but no viral genomes were detected. Open
      pericardectomy was performed and histopathologic examination of the resected
      thickened pericardium showed extensive fibrosis and hyaline degeneration. A
      combined infection with parvovirus B19 (PVB19) and human herpes virus 6 (HHV6;
      subtype B) was proven within the resected pericardium. We suggest that local HHV6
      induced immunosuppression enhanced the PVB19 infection, thus resulting in chronic
      infection and leading to constrictive pericarditis. 

PMID- 23864224
TI  - Epigenetic drug combination induces genome-wide demethylation and altered gene
      expression in neuro-ectodermal tumor-derived cell lines.
AB  - BACKGROUND: Epigenetic alterations are inherent to cancer cells, and epigenetic
      drugs are currently primarily used to treat hematological malignancies. Pediatric
      neuro-ectodermal tumors originate from neural crest cells and also exhibit
      epigenetic alterations involving e.g. apoptotic pathways, which suggests that
      these tumors may also be sensitive to epigenetic drugs. This notion prompted us
      to assess molecular and functional effects of low dosage epigenetic drugs in
      neuro-ectodermal tumor-derived cell lines of pediatric origin. RESULTS: In 17
      neuroblastoma (NBL) and 5 peripheral primitive neuro-ectodermal tumor (PNET) cell
      lines a combination treatment of 5-aza-2'-deoxycytidine (DAC) and Trichostatin A
      (TSA) at nanomolar dosages was found to reduce proliferation and to induce wide
      spread DNA demethylation, accompanied by major changes in gene expression
      profiles. Approximately half of the genes that were significantly up-regulated
      upon treatment exhibited a significant demethylation in their promoter regions.
      In the NBL cell lines, almost every cellular pathway (193/200) investigated
      showed expression alterations after treatment, especially a marked up-regulation
      of genes in the p53 pathway. The combination treatment also resulted in up
      regulation of known epigenetically regulated genes such as X-chromosomal genes,
      tissue-specific genes and a limited number of imprinted genes, as well as known
      tumor suppressor genes and oncogenes. CONCLUSIONS: Nanomolar dosages of
      epigenetic drugs have a dramatic impact on the genomes of neuro-ectodermal tumor
      derived cell lines, including alterations in DNA methylation and concomitant
      alterations in gene expression.

PMID- 23864225
TI  - Mechanism of activation of elongation factor Tu by ribosome: catalytic histidine
      activates GTP by protonation.
AB  - Elongation factor Tu (EF-Tu) is central to prokaryotic protein synthesis as it
      has the role of delivering amino-acylated tRNAs to the ribosome. Release of EF
      Tu, after correct binding of the EF-Tu:aa-tRNA complex to the ribosome, is
      initiated by GTP hydrolysis. This reaction, whose mechanism is uncertain, is
      catalyzed by EF-Tu, but requires activation by the ribosome. There have been a
      number of mechanistic proposals, including those spurred by a recent X-ray
      crystallographic analysis of a ribosome:EF-Tu:aa-tRNA:GTP-analog complex. In this
      work, we have investigated these and alternative hypotheses, using high-level
      quantum chemical/molecular mechanical simulations for the wild-type protein and
      its His85Gln mutant. For both proteins, we find previously unsuggested mechanisms
      as being preferred, in which residue 85, either His or Gln, directly assists in
      the reaction. Analysis shows that the RNA has a minor catalytic effect in the
      wild-type reaction, but plays a significant role in the mutant by greatly
      stabilizing the reaction's transition state. Given the similarity between EF-Tu
      and other members of the translational G-protein family, it is likely that these
      mechanisms of ribosome-activated GTP hydrolysis are pertinent to all of these
      proteins. 

PMID- 23864226
TI  - Predict subcellular locations of singleplex and multiplex proteins by semi
      supervised learning and dimension-reducing general mode of Chou's PseAAC.
AB  - Predicting protein subcellular location is one of major challenges in
      Bioinformatics area since such knowledge helps us understand protein functions
      and enables us to select the targeted proteins during drug discovery process.
      While many computational techniques have been proposed to improve predictive
      performance for protein subcellular location, they have several shortcomings. In
      this work, we propose a method to solve three main issues in such techniques; i)
      manipulation of multiplex proteins which may exist or move between multiple
      cellular compartments, ii) handling of high dimensionality in input and output
      spaces and iii) requirement of sufficient labeled data for model training.
      Towards these issues, this work presents a new computational method for
      predicting proteins which have either single or multiple locations. The proposed
      technique, namely iFLAST-CORE, incorporates the dimensionality reduction in the
      feature and label spaces with co-training paradigm for semi-supervised multi
      label classification. For this purpose, the Singular Value Decomposition (SVD) is
      applied to transform the high-dimensional feature space and label space into the
      lower-dimensional spaces. After that, due to limitation of labeled data, the co
      training regression makes use of unlabeled data by predicting the target values
      in the lower-dimensional spaces of unlabeled data. In the last step, the
      component of SVD is used to project labels in the lower-dimensional space back to
      those in the original space and an adaptive threshold is used to map a numeric
      value to a binary value for label determination. A set of experiments on viral
      proteins and gram-negative bacterial proteins evidence that our proposed method
      improve the classification performance in terms of various evaluation metrics
      such as Aiming (or Precision), Coverage (or Recall) and macro F-measure, compared
      to the traditional method that uses only labeled data.

PMID- 23864228
TI  - Calcium channel blockers as initial therapeutic agents in hypertension:
      relationship to incident heart failure.
AB  - Blood pressure (BP) control is central to health promotion and maintenance across
      the health care continuum. Optimal control has been associated with improved
      microvascular end organ outcomes, reduced morbidity and mortality, and improved
      quality of life. Calcium channel blockers (CCBs) are a frequently utilized first
      line antihypertensive agent, either as a monotherapy or in combination, as
      advocated by the 2003 Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC
      VII). However, despite their ability to achieve BP parameters comparable to
      alternative agents, CCBs may be inducing heart failure (HF) pathology by a
      mechanism other than the well-known negative inotropic effects of
      nondihydropyridine CCBs and thus may be responsible for more incident HF than was
      previously thought. Review of current literature indicates that there is a strong
      association between all types of CCBs and incident HF, that this association is
      found in persons with and without preexisting myocardial dysfunction, that BP
      measurement alone is an insufficient measure of end organ preservation with CCB
      use, and that CCB-induced HF is more problematic with comorbid coronary disease,
      renal disease, and diabetes mellitus. Furthermore, current research suggests that
      these outcomes are a result of CCB-induced neurohormonal sympathetic activation,
      sustained CCB-generated nitric oxide production leading to inflammation and
      tissue destruction, and/or increased systemic calcification secondary to
      concurrent calcium supplementation. These findings suggest the pressing need for
      reevaluation of CCBs as first-line agents in treating hypertension and for
      possible revision of JNC VII hypertension guidelines.

PMID- 23864227
TI  - Identification of fatigue biomarkers in treated and treatment-naive HIV patients:
      preliminary results.
AB  - Objective assessment in human immunodeficiency virus (HIV)-related fatigue has
      been elusive because the biological mechanisms are not well characterized. We
      tried to identify low-abundance plasma proteins that correlate with self-reported
      fatigue intensity in people living with HIV. We used plasma samples from 32
      patients with HIV with varying degrees of fatigue who were either treated with
      nucleoside reverse transcriptase inhibitors or treatment naive. The plasma
      samples were enriched for low-abundance proteins and trypsinized. The peptides
      were analyzed using shotgun proteomics. Five targets correlated with severity of
      fatigue: apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB), histine-rich
      glycoprotein, alpha-1 B glycoprotein, and orosomucoid 2. These targets were
      selected based on total abundance and spectral count differences, and ApoA1 and
      ApoB were analyzed via Western blots to verify the mass spectrometry results.
      ApoA1 levels were higher in untreated patients, while ApoB results suggested a
      possible positive trend in treated patients. Further analysis is needed to
      identify additional low-abundance proteins and confirm already-identified
      proteins as potential fatigue biomarkers.

PMID- 23864229
TI  - Introgression of stem rust resistance genes SrTA10187 and SrTA10171 from Aegilops
      tauschii to wheat.
AB  - Aegilops tauschii, the diploid progenitor of the wheat D genome, is a readily
      accessible germplasm pool for wheat breeding as genes can be transferred to elite
      wheat cultivars through direct hybridization followed by backcrossing. Gene
      transfer and genetic mapping can be integrated by developing mapping populations
      during backcrossing. Using direct crossing, two genes for resistance to the
      African stem rust fungus race TTKSK (Ug99), were transferred from the Ae.
      tauschii accessions TA10187 and TA10171 to an elite hard winter wheat line,
      KS05HW14. BC2 mapping populations were created concurrently with developing
      advanced backcross lines carrying rust resistance. Bulked segregant analysis on
      the BC2 populations identified marker loci on 6DS and 7DS linked to stem rust
      resistance genes transferred from TA10187 and TA10171, respectively. Linkage maps
      were developed for both genes and closely linked markers reported in this study
      will be useful for selection and pyramiding with other Ug99-effective stem rust
      resistance genes. The Ae. tauschii-derived resistance genes were temporarily
      designated SrTA10187 and SrTA10171 and will serve as valuable resources for stem
      rust resistance breeding. 

PMID- 23864231
TI  - Reflectance confocal microscopy features of Degos disease.

PMID- 23864230
TI  - Comparative mapping of Raphanus sativus genome using Brassica markers and
      quantitative trait loci analysis for the Fusarium wilt resistance trait.
AB  - Fusarium wilt (FW), caused by the soil-borne fungal pathogen Fusarium oxysporum
      is a serious disease in cruciferous plants, including the radish (Raphanus
      sativus). To identify quantitative trait loci (QTL) or gene(s) conferring
      resistance to FW, we constructed a genetic map of R. sativus using an F2 mapping
      population derived by crossing the inbred lines '835' (susceptible) and 'B2'
      (resistant). A total of 220 markers distributed in 9 linkage groups (LGs) were
      mapped in the Raphanus genome, covering a distance of 1,041.5 cM with an average
      distance between adjacent markers of 4.7 cM. Comparative analysis of the R.
      sativus genome with that of Arabidopsis thaliana and Brassica rapa revealed 21
      and 22 conserved syntenic regions, respectively. QTL mapping detected a total of
      8 loci conferring FW resistance that were distributed on 4 LGs, namely, 2, 3, 6,
      and 7 of the Raphanus genome. Of the detected QTL, 3 QTLs (2 on LG 3 and 1 on LG
      7) were constitutively detected throughout the 2-year experiment. QTL analysis of
      LG 3, flanked by ACMP0609 and cnu_mBRPGM0085, showed a comparatively higher
      logarithm of the odds (LOD) value and percentage of phenotypic variation. Synteny
      analysis using the linked markers to this QTL showed homology to A. thaliana
      chromosome 3, which contains disease-resistance gene clusters, suggesting
      conservation of resistance genes between them. 

PMID- 23864232
TI  - Interfrontal encephalocele: a rare feature of forehead in hydrocephalic
      myelomeningocele patients. Clinical feature, probable mechanisms, and management.
AB  - OBJECTIVE: Myelomeningocele is a complex central nervous system malformation
      mostly associated with other neural and extraneural anomalies. A rare special
      feature of the forehead and skull was observed in myelomeningocele. Here, we
      present several patients with myelomeningocele, severe hydrocephalus, and
      interfrontal encephalocele accompanied by metopic suture widening and abnormally
      shaped frontal bones. METHODS: Five children with this feature were enrolled in
      this series. The age, sex, location of myelomeningocele sac, neurological
      deficits, hydrocephalus and history of shunt surgery, and follow-up period were
      evaluated. RESULTS: Patients were aged from 1 to 12 months (mean, 6 months). All
      patients were male. Most sacs were located in lumbar and lumbosacral areas.
      Neurological deficits varying from only sphincter problem to paraplegia were
      found in all patients. Hydrocephalus was found in all children that needed a
      shunt procedure. Asymptomatic Chiari malformation, interfrontal encephalocele,
      and corpus callosum agenesis were evident in five, five, and three patients,
      respectively. CONCLUSION: Anterior fontanel anomalies known as interfrontal
      encephalocele associated with myelomeningocele have been reported before. The
      patients have an open metopic suture extending widely to the nasal radix
      producing hypertelorism accompanied by interfrontal herniation of frontal lobes.
      The associated hydrocephalus exaggerates the anomaly. Treatment of accompanying
      hydrocephalus is advised to decrease the severity of frontal lobe herniation.
      Some patients may need frontal bone reconstruction surgery to provide cosmetic
      correction at the place of the midline frontal bone defect.

PMID- 23864233
TI  - Association between serum uric acid and the metabolic syndrome among a middle-
      and old-age Chinese population.
AB  - Our aim was to study whether there is causal association between serum uric acid
      and metabolic syndrome (MetS). A cross-sectional study was performed, including a
      total of 27,009 subjects (23,345 subjects having uric acid data) from the
      Dongfeng-Tongji Cohort study. The MetS was defined by the International Diabetes
      Foundation criteria of 2005. Association analysis was performed by logistic
      regression. A genetic risk score was calculated by adding the uric acid
      increasing alleles in two SNPs (rs11722228 in SLC2A9 and rs2231142 in ABCG2)
      which were identified from our genome-wide association study on uric acid levels.
      The causal association was examined by mendelian randomization analysis. Among a
      middle- and old-age Chinese population, serum uric acid concentrations were
      strongly associated with the risk of MetS and its several components (P <
      0.0001). The effects were stronger in women than in men. Despite the lack of
      statistical significance, both SNPs exhibited a trend with increased MetS risk
      (rs11722228, OR = 1.06, 95 % CI 0.99-1.14; rs2231142, OR = 1.02, 95 % CI 0.95
      1.10), consistent with their increasing uric acid effects. Each additional uric
      acid increasing allele in the genetic risk score was associated with 3 %
      increased MetS risk (OR = 1.03, 95 % CI 0.98-1.09; P = 0.23). Further adjustment
      for serum uric acid attenuated the trend of individual SNP and genetic risk score
      with increased MetS risk (all OR < 1.0). These findings suggested that serum uric
      acid was associated with MetS risk in a middle- and old-age Chinese population.
      Whether this association was causal remained to be investigated in the future
      studies. 

PMID- 23864234
TI  - No evidence of a link between multiple sclerosis and the vaccine against the
      human papillomavirus.

PMID- 23864235
TI  - Genes expressed in blood link osteoarthritis with apoptotic pathways.
AB  - OBJECTIVE: To identify novel gene expression networks in blood of osteoarthritis
      patients compared to controls. METHODS: A comprehensive exploration of gene
      expression in peripheral blood was performed by microarray analysis for a subset
      of osteoarthritis patients from the Genetics osteoARthritis and Progression
      (GARP) study in comparison with sex and age-matched healthy controls. To identify
      pathways, we performed gene enrichment analyses (database for annotation,
      visualisation and integrated discovery and search tool for the retrieval of
      interacting genes). Quantitative PCR analysis in overlapping and in additional
      osteoarthritis samples was performed for prioritised genes to validate and
      replicate findings. Classification of cases and controls was explored by applying
      statistical models. RESULTS: 741 probes representing 694 unique genes were
      differentially expressed between cases and controls, including 86 genes expressed
      with at least a 1.5-fold difference. ATF4, GPR18 and H3F3B were among the top
      genes identified (p<4.5 * 10(-8)). We found that in the blood of osteoarthritis
      patients the apoptosis pathway, including the well-known gene CASP3, was
      significantly enriched among the differentially expressed genes. Our findings
      were validated in independent samples and when using a small subset of the
      validated genes, we could accurately distinguish patients from controls (area
      under the curve 98%). CONCLUSIONS: In the current study, we have identified
      specific gene expression networks, in the easily accessible tissue blood, which
      associated consistently with osteoarthritis among GARP study cases. Our data
      further hint at the relevance of apoptosis as an aetiological factor in
      osteoarthritis onset, thereby qualifying expression profiling of blood as a
      useful tool to understand the underlying molecular mechanisms of osteoarthritis.

PMID- 23864236
TI  - Efficacy and safety of strontium ranelate in the treatment of knee
      osteoarthritis: results of a double-blind randomised, placebo-controlled trial.

PMID- 23864237
TI  - Interleukin-6 acts locally on the growth plate to impair bone growth.

PMID- 23864238
TI  - Fetal outcomes after rituximab exposure in women with autoimmune vasculitis.

PMID- 23864239
TI  - Predominantly proinflammatory cytokines decrease after B cell depletion therapy
      in patients with primary Sjogren's syndrome.

PMID- 23864242
TI  - Surgical quality measurement: an evolving science.

PMID- 23864244
TI  - An unusual inflammatory hepatic lesion.

PMID- 23864245
TI  - Cystic lesions with suspected soft tissue infiltration.

PMID- 23864246
TI  - Presence of different genotypes of Helicobacter pylori in patients with chronic
      tonsillitis and sleep apnoea syndrome.
AB  - Helicobacter pylori, a well-known gastric pathogen, has been detected in the oral
      cavity and oropharynx in tonsillar tissue. In our study, the presence of H.
      pylori in the tonsillar tissue of patients with chronic tonsillitis and sleep
      apnoea syndrome (SAS) was investigated. The aim was to detect and genotype H.
      pylori for a collection of data supporting the possible role of H. pylori in the
      aetiology of chronic tonsillitis and SAS. Helicobacter pylori was detected by
      real-time polymerase chain reaction (rt-PCR). 89 patients, 60 with a diagnosis of
      chronic tonsillitis and 29 with SAS, were tested. In the chronic tonsillitis
      group, Helicobacter was detected in 48 (80 %) specimens, cagA gene was detected
      in 12 samples (25 %) and 12 samples were negative. In SAS group, Helicobacter was
      found in 24 samples (82.76 %), cagA gene was detected in 5 (20.83 %) and 5
      samples (17.24 %) were negative. Helicobacter pylori-specific immunoglobulins
      were tested by ELISA in the serum of 57 patients only with 41 (71.93 %) showing
      positive. Our results on H. pylori DNA detection and H. pylori seropositivity
      show 26.32 % discrepancy, slightly in favour of rt-PCR (15.79 % compared to 10.53
      %). The H. pylori presence in tonsillar tissue does not depend on the type of
      oropharyngeal disease (p = 0.756). This study shows that oropharynx constitutes
      an extragastric reservoir of H. pylori infection which could serve as an
      aetiopathogenetic factor for chronic tonsillitis and tonsillar hyperplasia by
      SAS. No conclusion has yet been drawn about the mechanism of the process.

PMID- 23864247
TI  - The influence of bacterial biofilm on the clinical outcome of chronic
      rhinosinusitis: a prospective, double-blind, scanning electron microscopy study.
AB  - The aim of this study was to assess the influence of bacterial biofilms in
      chronic rhinosinusitis (CRS) patients on the clinical outcomes following
      endoscopic sinus surgery (ESS). This was a prospective, double-blind study.
      Patients undergoing ESS, because of CRS, were recruited. Overall 80 patients were
      qualified. For each of these demographic, clinical and radiologic characteristics
      were recorded. During surgery each patient had at least 7 mucosal specimens taken
      to assess, using scanning electron microscopy, the possible presence of bacterial
      biofilms. Prior to mucosa specimen excision, swabs for bacteriological and fungal
      analyses were taken. Each patient underwent perioperative and follow-up
      assessment at 3 and 6 months post-ESS. Biofilms were found in 33 (41.3%) patients
      (study group). From among the 47 patients without the presence of biofilms, 33
      (control group) were taken to match the study group in age, gender and clinical
      characteristics. The intensity of subjective and objective CRS symptoms, as well
      as patient quality-of-life, did not correlate with the Lund and Mackay score (p >
      0.05). Analysis of variance showed that, in the control group or the group as a
      whole, the intensity of subjective and objective symptoms decreased (p < 0.05),
      and the quality-of-life increased with time (p < 0.05). In conclusion, biofilm
      positive patients tend to have a greater severity of disease preoperatively and
      continue to have persistent and more severe symptoms post-ESS. This study
      supports the role of biofilms in maintaining the chronic and recalcitrant nature
      of CRS. The lack of planktonic bacteria in post-operative sinus swabs does not
      rule out the presence of bacterial biofilms.

PMID- 23864248
TI  - Longitudinal dynamics of depressogenic personality and attachment dimensions in
      adolescence: an examination of associations with changes in depressive symptoms.
AB  - Depressogenic personality and attachment are two major factors related to the
      development of adolescents' depressive symptoms. However, no previous
      longitudinal studies have examined simultaneously both vulnerability factors in
      relationship to depressive symptoms. The present study examined associations
      between intra-individual change in adolescents' depressogenic personality
      orientations (i.e., sociotropy and autonomy), dimensions of mother-adolescent
      attachment (i.e., anxiety and avoidance), and depressive symptoms. The sample of
      the present research consisted of 289 high school students (mean age = 12.51
      years at Time 1, 66% female) participating in a 3-wave cohort-sequential design.
      Latent growth curve modeling revealed no significant intra-individual change in
      depressogenic personality orientations but significant changes in dimensions of
      attachment and symptoms of depression. Initial levels of sociotropy were not
      related significantly to changes in attachment dimensions and depressive
      symptoms. High initial levels of autonomy were associated with increases in
      attachment anxiety, attachment avoidance, and depressive symptoms. In addition,
      results suggested that the association between initial levels of autonomy and
      increases in depressive symptoms was mediated by increases in attachment anxiety
      and avoidance. The discussion focuses on the status of depressogenic personality
      and attachment as risk factors for depression.

PMID- 23864249
TI  - Comparison between zoledronic acid and clodronate in the treatment of prostate
      cancer patients with bone metastases.
AB  - The aim of this study is to compare the efficacy and safety between zoledronic
      acid (ZA) and clodronate (CA) in the treatment of bone metastases for prostate
      cancer patients. We conducted a prospective study in recruiting 137 prostate
      cancer patients with bone metastases from 2008 to 2010. All men were well
      responding to first-line hormone therapy (PSA < 2 ng/mL); Patients were randomly
      assigned to receive zoledronic acid (4 mg over a 30 min infusion) every 1 month
      or to take 4 tablets per day of clodronate (1,600 mg) for up to 3 years. Bone
      mineral density (BMD) was measured by dual-energy X-ray absorptiometry at femoral
      neck, lumbar spine, and total hip, together with visual analog scale score were
      evaluated on baseline and 6, 12, 24, and 36 months, respectively. Toxicity and
      skeletal-related events (SREs) happened in both groups during this period were
      recorded down and compared. The ZA group had better bone progression-free
      survival (BPFS) (31 months vs 22 months, P = 0.04), but no statistical evidence
      of benefit was observed in terms of overall survival rate. The ZA group
      significantly increased lumbar spine BMD (4.5 +/- 2.3 % vs CA group 2.3 +/- 3.9 %
      P = 0.03), had a better response on pain-relieve effect (92 vs 76 % P = 0.002)
      and a rapid pain palliation (9 months vs 13 months P = 0.03). The CA group
      reported more gastrointestinal cases. However, the ZA group required more dose
      modifications. As compared to clodronate, Zoledronic acid has advantages on
      extending BPFS, better bone pain control and lumbar spine BMD performance for
      prostate cancer patients with bone metastases. The overall survival rate and SREs
      rate are similar.

PMID- 23864250
TI  - A comparison of measured and estimated glomerular filtration rate for carboplatin
      dose calculation in stage I testicular seminoma.
AB  - Dose calculation of adjuvant carboplatin chemotherapy for stage I testicular
      seminoma, based on area under the concentration curve (AUC), incorporates the
      glomerular filtration rate (GFR). This retrospective study compares 'gold
      standard' (51)Cr-ethylenediamine tetraacetic acid ((51)Cr-EDTA) GFR measurements
      with renal function estimations derived from the Cockcroft-Gault, Jelliffe and
      Wright formulae. INCLUSION CRITERIA: stage I testicular seminoma treated with a
      single dose of carboplatin AUC7 at one centre in South Wales, UK, between 2005
      and 2011, with contemporaneous (51)Cr-EDTA GFR measurement and serum creatinine.
      Renal function estimates obtained using Cockcroft-Gault, Jelliffe and Wright
      formulae were analysed for bias (mean percentage error, MPE) and precision (mean
      absolute percentage error, MAPE) compared to the gold standard. Sixty-eight
      patients were identified, median age 40 (range 17-66), median creatinine 82
      (range 55-120). For the Cockcroft-Gault, Jelliffe and Wright formulae,
      respectively, MPE was +12.4, -32.3 and +8.8; MAPE was 16.0, 32.7 and 12.9; and
      substitution of the calculated GFR result for (51)Cr-EDTA measurement would have
      resulted in a >10% discrepancy in carboplatin dose in 41.1, 97.1 and 42.6% of
      patients (predominantly overdoses for the Cockcroft-Gault and Wright formulae,
      underdoses for the Jelliffe formula). Of the formulae analysed, none accurately
      correlated with (51)Cr-EDTA GFR measurements.

PMID- 23864251
TI  - Feasibility and efficacy of combined cisplatin plus irinotecan chemotherapy for
      gastroenteropancreatic neuroendocrine carcinomas.
AB  - No standard treatment is currently available for gastroenteropancreatic
      neuroendocrine carcinomas (GEP-NEC). Therefore, we conducted this study to
      evaluate the effect of the combination of irinotecan and cisplatin in the
      treatment of GEP-NECs. Clinical data of 16 locally advanced or metastatic GEP-NEC
      patients treated with irinotecan plus cisplatin regimen in our center from
      September 2009 to August 2011 were reviewed. The regimen included 2-week cycles
      of 180 mg/m(2) irinotecan and 50 mg/m(2) cisplatin on day 1. Median age was 57
      years. The overall response rate was 57.1%, with a disease control rate of 78.6%.
      One patient achieved pathologic complete response and underwent esophagectomy
      after chemotherapy. Two patients who had gotten progressive disease were given
      sequential octreotide long-acting release (LAR) treatment and got disease
      progression again within 1 month. Six patients who achieved disease control
      received octreotide LAR as maintenance treatment. The total number of cycles of
      octreotide was 41, with a median of 4.5 (3-20 cycles). The progression-free
      survival was 5.5 months, with overall survival of 10.6 months. Grades 3-4
      hematological adverse events (AEs) occurred in 10 patients (62.5%) and 3 patients
      (18.7%) suffered grades 3-4 non-hematological AEs; no patient died of AEs. The
      irinotecan plus cisplatin chemotherapy is moderately effective and tolerable well
      tolerated in advanced or metastatic GEP-NEC patients; octreotide LAR may be a
      good maintenance treatment and should be considered as a treatment option for
      these patients in the future.

PMID- 23864252
TI  - Response diversity of wild bees to overwintering temperatures.
AB  - Biodiversity can provide insurance against environmental change, but only if
      species differ in their response to environmental conditions (response
      diversity). Wild bees provide pollination services to wild and crop plants, and
      response diversity might insure this function against changing climate. To
      experimentally test the hypothesis that bee species differ in their response to
      increasing winter temperature, we stored cocoons of nine bee species at different
      temperatures during the winter (1.5-9.5  degrees C). Bee species differed
      significantly in their responses (weight loss, weight at emergence and emergence
      date). The developmental stage during the winter explained some of these
      differences. Bee species overwintering as adults generally showed decreased
      weight and earlier emergence with increasing temperature, whereas bee species
      overwintering in pre-imaginal stages showed weaker or even opposite responses.
      This means that winter warming will likely affect some bee species negatively by
      increasing energy expenditure, while others are less sensitive presumably due to
      different physiology. Likewise, species phenologies will respond differently to
      winter warming, potentially affecting plant-pollinator interactions. Responses
      are not independent of current flight periods: bees active in spring will likely
      show the strongest phenological advances. Taken together, wild bee diversity
      provides response diversity to climate change, which may be the basis for an
      insurance effect.

PMID- 23864253
TI  - Inter-specific territoriality in a Canis hybrid zone: spatial segregation between
      wolves, coyotes, and hybrids.
AB  - Gray wolves (Canis lupus) and coyotes (Canis latrans) generally exhibit
      intraspecific territoriality manifesting in spatial segregation between adjacent
      packs. However, previous studies have found a high degree of interspecific
      spatial overlap between sympatric wolves and coyotes. Eastern wolves (Canis
      lycaon) are the most common wolf in and around Algonquin Provincial Park (APP),
      Ontario, Canada and hybridize with sympatric gray wolves and coyotes. We
      hypothesized that all Canis types (wolves, coyotes, and hybrids) exhibit a high
      degree of spatial segregation due to greater genetic, morphologic, and ecological
      similarities between wolves and coyotes in this hybrid system compared with
      western North American ecosystems. We used global positioning system telemetry
      and probabilistic measures of spatial overlap to investigate spatial segregation
      between adjacent Canis packs. Our hypothesis was supported as: (1) the
      probability of locating wolves, coyotes, and hybrids within home ranges
      ([Formula: see text] = 0.05) or core areas ([Formula: see text] < 0.01) of
      adjacent packs was low; and (2) the amount of shared space use was negligible.
      Spatial segregation did not vary substantially in relation to genotypes of
      adjacent packs or local environmental conditions (i.e., harvest regulations or
      road densities). We provide the first telemetry-based demonstration of spatial
      segregation between wolves and coyotes, highlighting the novel relationships
      between Canis types in the Ontario hybrid zone relative to areas where wolves and
      coyotes are reproductively isolated. Territoriality among Canis may increase the
      likelihood of eastern wolves joining coyote and hybrid packs, facilitate
      hybridization, and could play a role in limiting expansion of the genetically
      distinct APP eastern wolf population.

PMID- 23864254
TI  - Treatment of mice with cromolyn sodium after reperfusion, but not prior to
      ischemia, attenuates small intestinal ischemia-reperfusion injury.
AB  - Stabilizing mast cells (MCs) can either inhibit or augment inflammation; however,
      how improved therapeutic benefits against small intestinal ischemia-reperfusion
      injury (IIRI) can be achieved by stabilizing MCs remains to be elucidated. The
      present study was designed to evaluate different treatments with cromolyn sodium
      (CS, an MC stabilizer), which was administrated either prior to ischemia or after
      reperfusion. Kunming mice were randomized into a sham-operated group (SH), a sole
      IIR group (M), in which mice were subjected to 30 min superior mesenteric artery
      occlusion followed by 3 day or 3 h reperfusion, or IIR, treated with CS 15 min
      prior to ischemia or 15 min after reperfusion in the PreCr and PostCr groups. The
      survival rate and Chiu's scores were evaluated. The levels of ET-1, histamine,
      TNF-alpha and IL-6, and expression of MC protease 7 (MCP7), MC counts and
      myeloperoxidase (MPO) activity were quantified. IIR resulted in severe injury as
      demonstrated by significant increases in mortality and injury score. IIR also led
      to substantial elevations in the levels of ET-1, histamine, TNF-alpha and IL-6,
      expression of MCP7, MC counts and MPO activities (P<0.05, M vs. SH groups). All
      biochemical changes were markedly reduced in the PostCr group (P<0.05, PostCr vs.
      M groups), whereas pretreatment of IIR mice with CS prior to ischemia exhibited
      no changes of ET-1 levels, injury score and inflammation (P>0.05, PreCr vs. M
      groups). In conclusion, administration of CS after reperfusion, but not prior to
      ischemia, attenuates IIRI by downregulating ET-1 and suppressing sustained MC
      activation.

PMID- 23864256
TI  - [Eulogy for Prof. Dr. Dieter Karch on the occasion of his appointment as an
      honorary member of the GNP at the 39th Annual Meeting of the Society for
      Pediatric Neurology in Innsbruck].

PMID- 23864257
TI  - [Euology for Prof. Dr. Horst Todt on the occasion of his appointment as an
      honorary memeber of the GNP at the 39th Annual Meeting of the Society for
      Pediatric Neurology in Innsbruck].

PMID- 23864258
TI  - Acute phase proteins response in hunting dogs.
AB  - Haptoglobin (Hp), serum amyloid A (SAA), C-reactive protein (CRP), and white
      blood cells (WBC) were assessed in 20 dogs divided into 2 groups. The dogs of
      group A were not subjected to hunting exercise (control group), while the dogs of
      group B were subjected to hunting exercise for 3 hr (experimental group). Blood
      samples were collected from each animal before hunting (T0), immediately after 3
      hr of hunting (T1), and after 1 hr of recovery (T2). The general linear model
      (GLM) repeated measures procedure showed a significant difference between the 2
      groups (P < 0.0001) and a significant rise (P < 0.0001) in concentration of Hp,
      SAA, and CRP after hunting exercise, with a consequent decline during recovery
      period in group B. These parameters could be considered valid and easily
      obtainable biomarkers in relation to hunting stress in dogs. Additional studies
      will continue to elucidate the magnitude and the time of response of other acute
      phase proteins. 

PMID- 23864259
TI  - Severe thymic hyperplasia in a newborn calf associated with impaired T-cell
      differentiation.
AB  - A 1-day-old female Holstein-Friesian calf was presented for severe dyspnea.
      Physical examination revealed respiratory distress, moderate edema of the ventral
      neck, and swollen jugular veins. The calf died and was submitted for necropsy. A
      severely enlarged thymus (40 cm * 20 cm * 10 cm) weighing 1.37 kg was detected on
      gross examination. Histomorphology was normal but no tingible body macrophages
      were observed in the medullary areas. Immunohistochemistry was characterized by
      the lack of thymic cluster of differentiation 3 and major histocompatibility
      complex class II expression compared to age-matched controls. The findings were
      consistent with severe thymic hyperplasia, a rare congenital condition that is
      also described in children. Immunohistochemical findings were suggestive of
      impaired T-cell development and selection associated with lack of apoptosis of
      thymic cells (lack of tingible body macrophages). Thymic hyperplasia in juvenile
      animals should be considered among the differential diagnoses of mediastinal
      masses as a rare cause of respiratory distress in newborn calves. 

PMID- 23864260
TI  - Ultrasound imaging method for internal jugular vein measurement and estimation of
      circulating blood volume.
AB  - PURPOSE: Evaluation of circulating blood volume is important in assessing the
      status of patients. Although some studies have suggested that ultrasound images
      of the internal jugular vein (IJV) can be used for the analysis of circulating
      blood volume, accurate extraction of IJV is necessary to reduce errors.
      Therefore, this study was designed to develop a new algorithm for dynamic
      segmentation of IJV and determine appropriate indicators to evaluate the
      circulating blood volume. METHODS: Our algorithm is based on snake and speckle
      tracking models. As the region of interest (ROI) of the control points of the
      snake tracking algorithm was dynamically moved using speckle tracking, ROI size
      can be decreased leading to a reduction in the tracking error. Some experiments
      were performed to validate our algorithm. Subsequently, the algorithm was used
      for the experiment simulating dehydration state among 11 subjects. RESULTS:
      Results of the validation experiment suggest that our algorithm showed higher
      performance for IJV extraction compared with standard methods. Furthermore, it
      was revealed that some indices such as the average area of IJV were related to
      the dehydration state of subjects. CONCLUSION: This study proposed a new
      algorithm, which was based on snake and speckle tracking models, for dynamic
      extraction of IJV in ultrasound images. In addition to algorithm validation, it
      was suggested that some indices the ultrasound image of IJV could be used for the
      evaluation of the circulating blood volume.

PMID- 23864261
TI  - A Tactile Stimulation Device for EEG Measurements in Clinical Use.
AB  - A tactile stimulation device for EEG measurements in clinical environments is
      proposed. The main purpose of the tactile stimulation device is to provide
      tactile stimulation to different parts of the body. To stimulate all four major
      types of mechanoreceptors, different stimulation patterns with frequencies in the
      range of 5-250 Hz have to be generated. The device provides two independent
      channels, delivers enough power to drive different types of electromagnetic
      transducers, is small and portable, and no expensive components are required to
      construct this device. The generated stimulation patterns are very stable, and
      deterministic control of the device is possible. To meet electrical safety
      requirements, the device was designed to be fully galvanically isolated. Leakage
      currents of the entire EEG measurement system including the tactile stimulation
      device were measured by the European Testing and Certifying Body for Medical
      Products Graz (Notified Body 0636). All measured currents were far below the
      maximum allowable currents defined in the safety standard EN 60601-1:2006 for
      medical electrical equipment. The successful operation of the tactile stimulation
      device was tested during an EEG experiment. The left and right wrist of one
      healthy subject were randomly stimulated with seven different frequencies. Steady
      state somatosensory evoked potential (SSSEPs) could successfully be evoked and
      significant tuning curves at electrode positions contralateral to the stimulated
      wrist could be found. The device is ready to be used in clinical environment in a
      variety of applications to investigate the somatosensory system, in brain
      computer interfaces (BCIs), or to provide tactile feedback.

PMID- 23864262
TI  - Enhancing isoprenoid production through systematically assembling and modulating
      efflux pumps in Escherichia coli.
AB  - Enhancement of the cellular exportation of heterologous compounds is an important
      aspect to improve the product yield in microbial cell factory. Efflux pumps can
      expel various intra- or extra-cellular substances out of microbial hosts and
      increase the cellular tolerance. Thus in this study, by using the hydrophobic
      sesquiterpene (amorphadiene) and diterpene (kaurene) as two model compounds, we
      attempted to improve isoprenoid production through systematically engineering the
      efflux pumps in Escherichia coli BL21(DE3). The pleiotropic resistant pumps,
      AcrAB-TolC, MdtEF-TolC from E. coli and heterologous MexAB-OprM pump from
      Pseudomonas aeruginosa, were overexpressed, assembled, and finely modulated. We
      found that overexpression of AcrB and TolC components can effectively enhance the
      specific yield of amorphadiene and kaurene, e.g., 31 and 37 % improvement for
      amorphadiene compared with control, respectively. The heterologous MexB component
      can enhance kaurene production with 70 % improvement which is more effective than
      TolC and AcrB. The results suggest that the three components of tripartite efflux
      pumps play varied effect to enhance isoprenoid production. Considering the highly
      organized structure of efflux pumps and importance of components interaction,
      various component combinations were constructed and the copy number of key
      components AcrB and TolC was finely modulated as well. The results exhibit that
      the combination TolC and TolC and AcrB improved the specific yield of
      amorphadiene with 118 %, and AcrA and TolC and AcrB improved that of kaurene with
      104 %. This study indicates that assembling and finely modulating efflux pumps is
      an effective strategy to improve the production of heterologous compounds in E.
      coli. 

PMID- 23864263
TI  - A comparison of visual and auditory representational momentum in spatial tasks.
AB  - Similarities have been observed in the localization of the final position of
      moving visual and moving auditory stimuli: Perceived endpoints that are judged to
      be farther in the direction of motion in both modalities likely reflect
      extrapolation of the trajectory, mediated by predictive mechanisms at higher
      cognitive levels. However, actual comparisons of the magnitudes of displacement
      between visual tasks and auditory tasks using the same experimental setup are
      rare. As such, the purpose of the present free-field study was to investigate the
      influences of the spatial location of motion offset, stimulus velocity, and
      motion direction on the localization of the final positions of moving auditory
      stimuli (Experiment 1 and 2) and moving visual stimuli (Experiment 3). To assess
      whether auditory performance is affected by dynamically changing binaural cues
      that are used for the localization of moving auditory stimuli (interaural time
      differences for low-frequency sounds and interaural intensity differences for
      high-frequency sounds), two distinct noise bands were employed in Experiments 1
      and 2. In all three experiments, less precise encoding of spatial coordinates in
      paralateral space resulted in larger forward displacements, but this effect was
      drowned out by the underestimation of target eccentricity in the extreme
      periphery. Furthermore, our results revealed clear differences between visual and
      auditory tasks. Displacements in the visual task were dependent on velocity and
      the spatial location of the final position, but an additional influence of motion
      direction was observed in the auditory tasks. Together, these findings indicate
      that the modality-specific processing of motion parameters affects the
      extrapolation of the trajectory. 

PMID- 23864264
TI  - Chasin' choppers: using unpredictable trajectories to test theories of object
      interception.
AB  - Three theories of the informational basis for object interception strategies were
      tested in an experiment where participants pursued toy helicopters. Helicopters
      were used as targets because their unpredictable trajectories have different
      effects on the optical variables that have been proposed as the basis of object
      interception, providing a basis for determining the variables that best explain
      this behavior. Participants pursued helicopters while the positions of both
      pursuer and helicopter were continuously monitored. Using models to predict the
      observed optical trajectories of the helicopter and ground positions of the
      pursuer, optical acceleration was eliminated as a basis of object interception. A
      model based on control of optical velocity (COV) provided the best match to
      pursuer ground movements, while one based on segments of linear optical
      trajectories (SLOT) provided the best match to the observed optical trajectories.
      We describe suggestions for further research to distinguish the COV and SLOT
      models. 

PMID- 23864265
TI  - Rapid volitional control of apparent motion during percept generation.
AB  - How rapidly can one voluntarily influence percept generation? The time course of
      voluntary visual-spatial attention is well studied, but the time course of
      intentional control over percept generation is relatively unknown. We
      investigated the latter question using "one-shot" apparent motion. When a
      vertical or horizontal pair of squares is replaced by its 90o-rotated version,
      the bottom-up signal is ambiguous. From this ambiguous signal, it is known that
      people can intentionally generate a percept of rotation in a desired direction
      (clockwise or counterclockwise). To determine the time course of this intentional
      control, we instructed participants to voluntarily induce rotation in a precued
      direction (clockwise rotation when a high-pitched tone was heard, and
      counterclockwise rotation when a low-pitched tone was heard), and then to report
      the direction of rotation that was actually perceived. We varied the delay
      between the instructional cue and the rotated frame (cue-lead time) from 0 to
      1,067 ms. Intentional control became more effective with longer cue-lead times
      (asymptotically effective at 533 ms). Notably, intentional control was reliable
      even with a zero cue-lead time; control experiments ruled out response bias and
      the development of an auditory-visual association as explanations. This
      demonstrates that people can interpret an auditory cue and intentionally generate
      a desired motion percept surprisingly rapidly, entirely within the subjectively
      instantaneous moment in which the visual system constructs a percept of apparent
      motion. 

PMID- 23864266
TI  - The source of dual-task limitations: serial or parallel processing of multiple
      response selections?
AB  - Although it is generally recognized that the concurrent performance of two tasks
      incurs costs, the sources of these dual-task costs remain controversial. The
      serial bottleneck model suggests that serial postponement of task performance in
      dual-task conditions results from a central stage of response selection that can
      only process one task at a time. Cognitive-control models, by contrast, propose
      that multiple response selections can proceed in parallel, but that serial
      processing of task performance is predominantly adopted because its processing
      efficiency is higher than that of parallel processing. In the present study, we
      empirically tested this proposition by examining whether parallel processing
      would occur when it was more efficient and financially rewarded. The results
      indicated that even when parallel processing was more efficient and was
      incentivized by financial reward, participants still failed to process tasks in
      parallel. We conclude that central information processing is limited by a serial
      bottleneck. 

PMID- 23864268
TI  - From Formation to Ecosystem: Tansley's Response to Clements' Climax.
AB  - Arthur G. Tansley never accepted Frederic E. Clements' view that succession is a
      developmental process whose final stage, the climax formation, is determined
      primarily by regional climate and that all other types of vegetation are some
      kind of successional stage or arrested successional stage. Tansley was convinced
      that in a given region a variety of environmental factors could produce different
      kinds of climax formations. At the heart of their dispute was Clements'
      organicist view of succession, i.e., the formation was a complex organism with an
      ontogeny and phylogeny. As early as 1905, Tansley offered an alternative to
      Clements' complex organism, the quasi-organism, but Clements in private and
      public rejected this compromise. Tansley and other plant ecologists continued to
      criticize Clements' theories for the next 20 years, but with no impact on
      Clements. John Phillips, a South African plant ecologist who was a follower of
      Clements, published a series of papers in 1934 and 1935 defending Clementsian
      ecology. These papers were triggered by the publication of a letter by another
      ecologist working in Africa who claimed that there was a strong correlation
      between soils and various kinds of climax vegetation, which was contrary to what
      was predicted by Phillips and Clements. In 1935, Tansley published an attack on
      Phillips and Clements and their developmental theory of succession. In it, he
      proposed the concept of the ecosystem as a way to get around Clements' monoclimax
      theory by making the physical environment (e.g., soil chemistry, soil texture,
      soil moisture) as important a factor as climate, plants and other organisms in
      determining the composition and characteristics of ecological entities, i.e.,
      ecosystems. Tansley's ecosystem concept quickly replaced Clements' monoclimax
      theory as a dominant paradigm in ecology. 

PMID- 23864267
TI  - Vascular smooth muscle function in type 2 diabetes mellitus: a systematic review
      and meta-analysis.
AB  - AIMS/HYPOTHESIS: In type 2 diabetes, in contrast to the well-documented
      endothelial dysfunction, studies assessing vascular smooth muscle (VSM) function
      have yielded discrepant results over the last two decades. We therefore sought to
      determine whether or not VSM function is impaired in individuals with type 2
      diabetes. METHODS: We conducted a systematic search of MEDLINE, Cochrane, Scopus
      and Web of Science databases, from their respective inceptions until December
      2012, for articles evaluating VSM function in individuals with type 2 diabetes. A
      meta-analysis was performed to compare the standardised mean difference (SMD) in
      VSM function between individuals with type 2 diabetes and age-matched controls.
      Subgroup analyses and meta-regression were used to identify sources of
      heterogeneity. RESULTS: Twenty-seven articles (1,042 individuals with type 2
      diabetes and 601 control subjects) were included in this analysis. VSM function
      was significantly impaired in diabetic compared with control subjects (SMD -0.68,
      95% CI -0.84, -0.52; p < 0.001). Although moderate heterogeneity among studies
      was found (I (2) = 52%), no significant publication bias was detected. Subgroup
      analyses showed a further decline in VSM function assessed in the
      microcirculation compared with the macrocirculation of individuals with type 2
      diabetes (p = 0.009). In meta-regression, VSM function in the microcirculation
      was inversely associated with BMI and triacylglycerols and was positively
      associated with HDL-cholesterol. CONCLUSIONS/INTERPRETATION: In addition to the
      endothelium, the VSM is a source of vascular dysfunction in type 2 diabetes. An
      exacerbation of VSM function in the microcirculation may be a distinctive feature
      in type 2 diabetes.

PMID- 23864269
TI  - Retraction Note to: A case of nodular fasciitis in the upper eyelid (Jpn J
      Ophthalmol. 2009;53:546-8).

PMID- 23864271
TI  - Approximation-based adaptive neural control design for a class of nonlinear
      systems.
AB  - This paper focuses on approximation-based adaptive neural control of a class of
      nonlinear non-strict-feedback systems. Based on the structural characteristic and
      the monotonously increasing property of the system bounding functions, a variable
      separation method is first developed. By this method, an approximation-based
      adaptive backstepping approach is proposed for a class of nonlinear non-strict
      feedback systems. It is shown that the proposed controller guarantees semi-global
      boundedness of all the signals in the closed-loop systems. Three examples are
      used to illustrate the effectiveness of the proposed approach. 

PMID- 23864270
TI  - Choroidal thickness in pregnant women measured by enhanced depth imaging optical
      coherence tomography.
AB  - PURPOSE: To measure choroidal thickness in healthy pregnant women using enhanced
      depth imaging optical coherence tomography (EDI-OCT) and compare the measurements
      with those of healthy non-pregnant women. METHODS: Choroidal thickness was
      measured at the fovea and at 3 mm superior, inferior, temporal, and nasal to the
      fovea using EDI-OCT in both healthy pregnant and non-pregnant women. RESULTS: The
      mean choroidal thickness in pregnant women was 275 +/- 84 MUm at the subfoveal
      and 307 +/- 89, 277 +/- 89, 274 +/- 74, and 159 +/- 60 MUm at 3 mm superior,
      inferior, temporal, and nasal to the fovea, respectively. In comparison, the mean
      choroidal thickness in non-pregnant women was 273 +/- 92 MUm at the subfoveal and
      301 +/- 73, 290 +/- 76, 293 +/- 77, and 149 +/- 55 MUm at 3 mm superior,
      inferior, temporal, and nasal to the fovea, respectively. No significant
      statistical differences were found for choroidal thickness between the pregnant
      and non-pregnant women at any of the measurement points. CONCLUSIONS: The results
      of this study demonstrate that the choroidal thickness was not significantly
      different between healthy pregnant and non-pregnant women.

PMID- 23864272
TI  - Extremely high-dimensional feature selection via feature generating samplings.
AB  - To select informative features on extremely high-dimensional problems, in this
      paper, a sampling scheme is proposed to enhance the efficiency of recently
      developed feature generating machines (FGMs). Note that in FGMs O(mlogr) time
      complexity should be taken to order the features by their scores; the entire
      computational cost of feature ordering will become unbearable when m is very
      large, for example, m > 10(11) , where m is the feature dimensionality and r is
      the size of the selected feature subset. To solve this problem, in this paper, we
      propose a feature generating sampling method, which can reduce this computational
      complexity to O(Gslog(G)+G(G+log(G))) while preserving the most informative
      features in a feature buffer, where Gs is the maximum number of nonzero features
      for each instance and G is the buffer size. Moreover, we show that our proposed
      sampling scheme can be deemed as the birth-death process based on random
      processes theory, which guarantees to include most of the informative features
      for feature selections. Empirical studies on real-world datasets show the
      effectiveness of the proposed sampling method. 

PMID- 23864274
TI  - Incident lacunes preferentially localize to the edge of white matter
      hyperintensities: insights into the pathophysiology of cerebral small vessel
      disease.
AB  - White matter hyperintensities and lacunes are among the most frequent
      abnormalities on brain magnetic resonance imaging. They are commonly related to
      cerebral small vessel disease and associated with both stroke and dementia. We
      examined the spatial relationships between incident lacunes and white matter
      hyperintensities and related these findings to information on vascular anatomy to
      study possible mechanistic links between the two lesion types. Two hundred and
      seventy-six patients with cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL), a genetically defined
      small vessel disease with mutations in the NOTCH3 gene were followed with
      magnetic resonance imaging over a total of 633 patient years. Using difference
      images and Jacobian maps from registered images we identified 104 incident
      lacunes. The majority (n = 95; 91.3%) of lacunes developed at the edge of a white
      matter hyperintensity whereas few lacunes were found to develop fully within (n =
      6; 5.8%) or outside (n = 3; 2.9%) white matter hyperintensities. Adding
      information on vascular anatomy revealed that the majority of incident lacunes
      developed proximal to a white matter hyperintensity along the course of
      perforating vessels supplying the respective brain region. We further studied the
      spatial relationship between prevalent lacunes and white matter hyperintensities
      both in 365 patients with CADASIL and in 588 elderly subjects from the Austrian
      Stroke Prevention Study. The results were consistent with the results for
      incident lacunes. Lesion prevalence maps in different disease stages showed a
      spread of lesions towards subcortical regions in both cohorts. Our findings
      suggest that the mechanisms of lacunes and white matter hyperintensities are
      intimately connected and identify the edge of white matter hyperintensities as a
      predilection site for lacunes. Our observations further support and refine the
      concept of the white matter hyperintensity penumbra. 

PMID- 23864275
TI  - Apraxia in left-handers.
AB  - In typical right-handed patients both apraxia and aphasia are caused by damage to
      the left hemisphere, which also controls the dominant right hand. In left-handed
      subjects the lateralities of language and of control of the dominant hand can
      dissociate. This permits disentangling the association of apraxia with aphasia
      from that with handedness. Pantomime of tool use, actual tool use and imitation
      of meaningless hand and finger postures were examined in 50 consecutive left
      handed subjects with unilateral hemisphere lesions. There were three aphasic
      patients with pervasive apraxia caused by left-sided lesions. As the dominant
      hand is controlled by the right hemisphere, they constitute dissociations of
      apraxia from handedness. Conversely there were also three patients with pervasive
      apraxia caused by right brain lesions without aphasia. They constitute
      dissociations of apraxia from aphasia. Across the whole group of patients
      dissociations from handedness and from aphasia were observed for all
      manifestations of apraxia, but their frequency depended on the type of apraxia.
      Defective pantomime and defective tool use occurred rarely without aphasia,
      whereas defective imitation of hand, but not finger, postures was more frequent
      after right than left brain damage. The higher incidence of defective imitation
      of hand postures in right brain damage was mainly due to patients who had also
      hemi-neglect. This interaction alerts to the possibility that the association of
      right hemisphere damage with apraxia has to do with spatial aptitudes of the
      right hemisphere rather than with its control of the dominant left hand.
      Comparison with data from right-handed patients showed no differences between the
      severity of apraxia for imitation of hand or finger postures, but impairment on
      pantomime of tool use was milder in apraxic left-handers than in apraxic right
      handers. This alleviation of the severity of apraxia corresponded with a similar
      alleviation of the severity of aphasia as manifested by a lower proportion of
      left-handed patients with global aphasia. 

PMID- 23864273
TI  - Non-myeloablative autologous haematopoietic stem cell transplantation expands
      regulatory cells and depletes IL-17 producing mucosal-associated invariant T
      cells in multiple sclerosis.
AB  - Autologous haematopoietic stem cell transplantation has been tried as one
      experimental strategy for the treatment of patients with aggressive multiple
      sclerosis refractory to other immunotherapies. The procedure is aimed at ablating
      and repopulating the immune repertoire by sequentially mobilizing and harvesting
      haematopoietic stem cells, administering an immunosuppressive conditioning
      regimen, and re-infusing the autologous haematopoietic cell product. 'Non
      myeloablative' conditioning regimens to achieve lymphocytic ablation without
      marrow suppression have been proposed to improve safety and tolerability. One
      trial with non-myeloablative autologous haematopoietic stem cell transplantation
      reported clinical improvement and inflammatory stabilization in treated patients
      with highly active multiple sclerosis. The aim of the present study was to
      understand the changes in the reconstituted immune repertoire bearing potential
      relevance to its mode of action. Peripheral blood was obtained from 12 patients
      with multiple sclerosis participating in the aforementioned trial and
      longitudinally followed for 2 years. We examined the phenotype and function of
      peripheral blood lymphocytes by cell surface or intracellular staining and multi
      colour fluorescence activated cell sorting alone or in combination with
      proliferation assays. During immune reconstitution post-transplantation we
      observed significant though transient increases in the proportion of CD4+ FoxP3+
      T cells and CD56(high) natural killer cell subsets, which are cell subsets
      associated with immunoregulatory function. CD8+ CD57+ cytotoxic T cells were
      persistently increased after therapy and were able to suppress CD4+ T cell
      proliferation with variable potency. In contrast, a CD161(high) proinflammatory
      CD8+ T cell subset was depleted at all time-points post-transplantation.
      Phenotypic characterization revealed that the CD161(high)CD8+ T cells were
      mucosal-associated invariant T cells, a novel cell population originating in the
      gut mucosa but expressing the central nervous system-homing receptor CCR6.
      Detection of mucosal-associated invariant T cells in post-mortem multiple
      sclerosis brain white matter active lesions confirmed their involvement in the
      disease pathology. Intracellular cytokine staining demonstrated interferon gamma
      and interleukin 17 production and lack of interleukin 10 production, a pro
      inflammatory profile. Mucosal-associated invariant T cell frequency did not
      change in patients treated with interferon beta; and was more depleted after
      autologous haematopoietic stem cell transplantation than in patients who had
      received high-dose cyclophosphamide (n = 7) or alemtuzumab (n = 21) treatment
      alone, suggesting an additive or synergistic effect of the conditioning regime
      components. We propose that a favourably modified balance of regulatory and pro
      inflammatory lymphocytes underlies the suppression of central nervous system
      inflammation in patients with multiple sclerosis following non-myeloablative
      autologous haematopoietic stem cell transplantation with a conditioning regimen
      consisting of cyclophosphamide and alemtuzumab.

PMID- 23864276
TI  - The pediatrician's role in educating parents on disciplinary modalities:
      identifying weaknesses and heightening awareness.

PMID- 23864277
TI  - Laparoscopic percutaneous extraperitoneal closure for inguinal hernia: learning
      curve for attending surgeons and residents.
AB  - BACKGROUND/PURPOSE: Laparoscopic percutaneous extraperitoneal closure (LPEC) for
      pediatric inguinal hernia is a simple technique in which a purse-string suture
      made of nonabsorbable material is placed extraperitoneally around the hernia
      orifice by a special suture needle (LapaherclosureTM). Concerns have been raised
      about the extensive learning curve for both attending surgeons and residents to
      master this technique. This study assesses the difference in learning curves for
      the safe performance of LPEC by attending surgeons and residents. METHODS: A
      retrospective analysis was performed on the surgical charts of 409 consecutive
      patients (175 girls, 234 boys) who had undergone LPEC for inguinal hernia repair
      from December 2005 to December 2011 at Jikei University Hospital. The number of
      operation needed by attending surgeons and residents to reach the appropriate
      operation time was analyzed by the Mann-Whitney U test. RESULTS: LPEC was
      performed by three attending surgeons and four residents who had not previously
      performed LPEC. The standard operation time for LPEC by attending surgeons who
      have performed more than 100 LPEC cases safely is 30 min. In our study, the
      attending surgeons needed a mean of 12 operations (range, 10-16) to reach 30 min
      for LPEC. Three residents needed a mean of 31 operations (range, 27-33) to reach
      30 min for LPEC. The fourth resident could not perform LPEC in 30 min or less.
      The difference between the number of operations needed by the attending surgeons
      and the residents to perform LPEC safely was statistically significant (P <
      0.05). The overall incidence of contralateral patent processus vaginalis was 47.9
      %. CONCLUSIONS: Our learning curve analysis showed that whereas attending
      surgeons needed a mean of 12 operations to perform LPEC repairs safely in 30 min
      or less, residents needed more than 30 operations to safely perform LPEC repairs
      without supervision.

PMID- 23864278
TI  - Embryonal sarcoma of the liver.
AB  - PURPOSE: Embryonal sarcoma accounts for 6 % of liver tumors. This study reviews
      its features and the results of treatment in a referral center. METHODS: We
      retrospectively reviewed liver tumors treated between 1995 and 2011. PRETEXT
      staging and biopsy were used to tailor chemotherapy according to SIOP protocols.
      Radical surgery was performed when possible. Complications and cumulative
      survival were the outcome endpoints. RESULTS: Six out of 156 primary liver tumors
      (four males and two females) were sarcomas. The mean age at diagnosis was 81 +/-
      8.5 months. The most frequent finding was abdominal mass. Alfa-fetoprotein was
      normal. Imaging depicted heterogeneous tumors with septa, necrosis, and
      hemorrhagic areas. The diagnosis was ascertained by biopsy. Three tumors were
      located in the right lobe (PRETEXT II): two were bilobar (PRETEXT III) and one
      was in the left lobe (PRETEXT I). Two children had metastases at diagnosis and
      high-risk chemotherapy (vincristine, carboplatin, epirubicin) was administered
      with poor response. They died without operation 4 and 10 months later. Four
      patients with local disease underwent typical liver resections after chemotherapy
      (iphosphamide, vincristine, actinomycin D, and doxorrubicin). Overall actuarial
      survival at 70 months was 66.6 %. CONCLUSIONS: Extended and metastatic embryonal
      sarcoma do poorly whereas localized tumors amenable to complete surgical removal
      after chemotherapy can cure.

PMID- 23864279
TI  - Microvesicle microRNA profiles and functional roles between chronic hepatitis B
      and hepatocellular carcinoma.
AB  - OBJECTIVES: Hepatocellular carcinoma (HCC) is an inflammation-related malignancy
      and chronic hepatitis B (CHB) predisposes to HCC. Microvesicles (MVs) transfer
      various bioactive molecules including microRNA (miRNA) between cells and exert
      biological functions. The purpose of this study was to detect CHB-MV and HCC-MV
      miRNAs and analyze the expression profiles and functional roles between CHB and
      HCC. METHODS: We examined MV miRNA profiles of CHB and HCC using miRNA
      microarrays. TargetScan, PicTar and miRanda were exerted to predict target genes
      regulating these differentially expressed miRNAs. RESULTS: A total of 272 and 242
      aberrant fluctuation miRNAs were identified in CHB-MVs and HCC-MVs, respectively.
      Among them, there were 53 miRNAs co-expressing both in CHB-MVs and HCC-MVs. These
      miRNAs affected cellular apoptosis, proliferation and molecular signaling
      pathways. Among them, 25 co-expressed MV miRNAs targeted 21 inflammatory factors
      and these miRNAs may be a tight linkage between CHB and HCC. Interestingly, there
      were 14 co-expressed MV miRNAs targeting 17 oncogenes and 7 miRNAs targeting 9
      tumor suppressors in the study. In addition, MVs were enriched with maladjusted
      miRNAs regulating zinc finger proteins and chromosome open reading frame. Those
      MV miRNAs may play roles in CHB developing to HCC. CONCLUSIONS: We demonstrated
      that CHB and HCC displayed aberrantly co-expressed MV miRNA profiles for the
      first time, which may have a link between CHB and HCC. Those MV miRNAs may serve
      as early biomarkers for HCC and may aid to promote CHB developing to HCC.

PMID- 23864280
TI  - Generation of porcine fibroblasts overexpressing 11beta-HSD1 with adipose tissue
      specific aP2 promoter as a porcine model of metabolic syndrome.
AB  - Metabolic syndrome arises from a combination of disorders that increase the risk
      of cardiovascular disease and diabetes. In previous studies, it was observed that
      overexpression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1)
      induced obesity and the insulin resistance that accompanies metabolic syndrome in
      rodent adipose tissue. Based on these observations, it was hypothesized that
      overexpression of 11beta-HSD1 may be suitable for the generation of a porcine
      model of metabolic syndrome. It was evaluated that promoter activities of the
      porcine adipose fatty acid-binding protein (aP2) gene generates adipose tissue
      specific 11beta-HSD1 expression. In adipose tissue, the maximum promoter activity
      (-2,826 to +51 nt) of aP2 was 200-fold higher than that of a promoterless
      construct. In addition, 11beta-HSD1 transcriptional levels were significantly
      increased following the introduction of the aP2 promoter into 3T3-L1 adipocytes.
      These observations indicate that the aP2 promoter may facilitate 11beta-HSD1
      overexpression in porcine adipose tissue. Transgenic fibroblasts were generated
      containing 11beta-HSD1 cDNA controlled by the aP2 promoter with two screening
      markers, green fluorescence protein and a neomycin-resistance gene. It was
      hypothesized that transgenic fibroblasts may be useful for generating a porcine
      model of metabolic syndrome.

PMID- 23864281
TI  - Working memory and insight in verbal problems: analysis of compound remote
      associates.
AB  - Problem solving is sometimes accompanied by a sudden feeling of knowing, or
      insight. The specific cognitive processes that underlie insightful problem
      solving are a matter of great interest and debate. Although some investigators
      favor a special-process view, which explains insight in terms of specialized
      mechanisms that operate outside of conscious awareness, others favor a business
      as-usual account, which posits that insightful problem solving involves the same
      conscious mechanisms-including working memory (WM) and attention-that are
      implicated in noninsightful problem solving. In the present study, we used an
      individual-differences approach to explore the contributions of WM and attention
      to the solution of compound remote associate (CRA) problems. On the basis of self
      report insight ratings, we identified CRA problems whose solution was accompanied
      by a subjective feeling of insight and examined the correlations between problem
      performance and measures of WM capacity (verbal and spatial) and attention
      control (Stroop and antisaccade tasks). The results indicated that individual
      differences in verbal WM and attention significantly explained variation in
      overall CRA problem solving and, most importantly, in the occurrence of solutions
      that were accompanied by a feeling of insight. The findings implicated both
      modality-dependent WM mechanisms and modality-independent attention control
      mechanisms in this class of insight problems. Comparisons of the accuracy and
      solution-latency findings for insightfully versus noninsightfully solved CRA
      problems, and for participants working silently versus in a "think-aloud"
      condition, provided additional evidence against the special-process view, and
      reinforcing the business-as-usual account of insight. 

PMID- 23864282
TI  - Do Heliconius butterfly species exchange mimicry alleles?
AB  - Hybridization has the potential to transfer beneficial alleles across species
      boundaries, and there are a growing number of examples in which this has
      apparently occurred. Recent studies suggest that Heliconius butterflies have
      transferred wing pattern mimicry alleles between species via hybridization, but
      ancestral polymorphism could also produce a signature of shared ancestry around
      mimicry genes. To distinguish between these alternative hypotheses, we measured
      DNA sequence divergence around putatively introgressed mimicry loci and compared
      this with the rest of the genome. Our results reveal that putatively introgressed
      regions show strongly reduced sequence divergence between co-mimetic species,
      suggesting that their divergence times are younger than the rest of the genome.
      This is consistent with introgression and not ancestral variation. We further
      show that this signature of introgression occurs at sites throughout the genome,
      not just around mimicry genes. 

PMID- 23864284
TI  - Regulation of transcription from two ssrS promoters in 6S RNA biogenesis.
AB  - ssrS-encoded 6S RNA is an abundant noncoding RNA that binds sigma(70)-RNA
      polymerase and regulates expression at a subset of promoters in Escherichia coli.
      It is transcribed from two tandem promoters, ssrS P1 and ssrS P2. Regulation of
      transcription from two ssrS promoters in 6S RNA biogenesis was examined. Both P1
      and P2 were growth phase-dependently regulated. Depletion of 6S RNA had no effect
      on growth-phase-dependent transcription from either promoter, whereas
      overexpression of 6S RNA increased P1 transcription and decreased P2
      transcription, suggesting that transcription from P1 and P2 is subject to
      feedback activation and feedback inhibition, respectively. This feedback
      regulation disappeared in Deltafis strains, supporting involvement of Fis in this
      process. The differential feedback regulation may provide a means for maintaining
      appropriate cellular concentrations of 6S RNA. 

PMID- 23864285
TI  - Early and late inner retinal changes after inner limiting membrane peeling.
AB  - Pars plana vitrectomy and inner limiting membrane (ILM) peeling are standard
      procedures for macular hole and epiretinal membrane surgery. However, ILM peeling
      is known to cause mechanical traumatic changes to the retinal nerve fiber layer.
      Recently there have been numerous reports of anatomical changes in the macula
      after ILM removal. A comprehensive review of the literature. The earliest change
      in the macula after ILM peeling is post-operative swelling of the arcuate retinal
      nerve fiber layer (SANFL), which disappears within the 3 month; the swelling is
      not detected on biomicroscopic fundus examination but appears as
      hypoautofluorescent arcuate striae in the macular region on infrared and
      autofluorescence imaging, with corresponding hyperreflectant swelling
      demonstrated on spectral-domain optical coherence tomography (OCT). SANFL is
      followed by dissociated optic nerve fiber layer defect, faintly visible on fundus
      examination and corresponding on OCT to "dimples" in the inner retinal layers.
      The en face tomographic aspect of this defect appears as concentric macular dark
      spots. Post-operative foveal displacement toward the optic disc might be
      responsible for the stretching and thinning of the retinal parenchyma in the
      temporal subfield and the thickening of the nasal macula. This shortening of the
      papillofoveal distance after surgery is probably secondary to axonal transport
      and contractility alterations in the nerve fiber layer, which might also account
      for apoptotic and atrophic degeneration of the peripapillary retinal nerve fiber
      layer. Ganglion cells do not seem to be affected by ILM peeling, even if the
      ganglion cell complex loses some volume because of trauma to the Muller cells
      contained in the ganglion cell layer. Despite its clear indication in macular
      hole and epiretinal membrane surgery, ILM peeling is a traumatic procedure that
      has acute effects on the underlying inner retinal layers. Further investigation
      of these subclinical changes may assist in aiding the development of minimally
      traumatic techniques for ILM removal.

PMID- 23864286
TI  - Effects of training experienced teachers in the use of the one-minute preceptor
      technique in the gross anatomy laboratory.
AB  - The one-minute preceptor (OMP) is a time-efficient, learner-centered teaching
      method used in a busy ambulatory care setting. This project evaluated the effects
      of training experienced anatomy teachers in the use of the OMP in the gross
      anatomy laboratory on students' perceived learning. Second-year medical students
      from a five-year, undergraduate-entry, system- and problem-based medical program
      were divided randomly into two groups of 76 students each. The groups took part
      in the same gross anatomy laboratory session on different dates, supervised by
      the same two teachers (both with over 25 years of teaching experience). The
      teachers attended a workshop on the use of the OMP between the two sessions.
      Students were given a questionnaire at the end of the two sessions to indicate
      their agreements to statements regarding their learning experiences.
      Semistructured interviews were conducted with the two teachers after the second
      session. Results showed that training experienced anatomy teachers in the use of
      the OMP did not result in improvement of student learning perception in the gross
      anatomy laboratory. The experienced teachers have developed their own approaches
      with elements similar to those in the OMP: being learner centered and adaptable
      to individual student's needs, providing feedback, and enhancing teacher
      immediacy. They do not have an explicit structure such as the OMP, and are thus
      flexible and adaptive. Confining the teachers' teaching behaviors to the OMP
      structure could limit their performance. Although there are theoretical
      advantages for novice teachers in adopting the OMP technique, these advantages
      still need to be supported by further studies.

PMID- 23864287
TI  - In vitro correction of a pseudoexon-generating deep intronic mutation in LGMD2A
      by antisense oligonucleotides and modified small nuclear RNAs.
AB  - Limb-girdle muscular dystrophy type 2A (LGMD2A) is the most frequent autosomal
      recessive muscular dystrophy. It is caused by mutations in the calpain-3 (CAPN3)
      gene. The majority of the mutations described to date are located in the coding
      sequence of the gene. However, it is estimated that 25% of the mutations are
      present at exon-intron boundaries and modify the pre-mRNA splicing of the CAPN3
      transcript. We have previously described the first deep intronic mutation in the
      CAPN3 gene: c.1782+1072G>C mutation. This mutation causes the pseudoexonization
      of an intronic sequence of the CAPN3 gene in the mature mRNA. In the present
      work, we show that the point mutation generates the inclusion of the pseudoexon
      in the mRNA using a minigene assay. In search of a treatment that restores normal
      splicing, splicing modulation was induced by RNA-based strategies, which included
      antisense oligonucleotides and modified small-nuclear RNAs. The best effect was
      observed with antisense sequences, which induced pseudoexon skipping in both HeLa
      cells cotransfected with mutant minigene and in fibroblasts from patients.
      Finally, transfection of antisense sequences and siRNA downregulation of
      serine/arginine-rich splicing factor 1 (SRSF1) indicate that binding of this
      factor to splicing enhancer sequences is involved in pseudoexon activation. 

PMID- 23864288
TI  - Phase 1 clinical trials in end-stage cancer: patient understanding of trial
      premises and motives for participation.
AB  - BACKGROUND: In cancer, phase 1 clinical trials on new drugs mostly involve
      patients with advanced disease that is unresponsive to standard therapy. The
      purpose of this study was to explore the difficult ethical problems related to
      patient information and motives for participation in such trials. METHOD: A
      descriptive and explorative qualitative design was used. Fourteen cancer patients
      from three different phase 1 trials in end-stage cancer were interviewed. The
      interviews were analysed using qualitative content analysis. RESULTS: The
      patients expressed unrealistic expectations of therapeutic benefit and inadequate
      understanding of the trials' purpose, so-called therapeutic misconception.
      However, they reported a positive attitude towards participation. Thus, the
      patients valued the close and unique medical and psychological attention they
      received by participating. Participation also made them feel unique and notable.
      CONCLUSIONS: Patients with end-stage cancer participating in phase 1 clinical
      trials are unaware of the very small potential for treatment benefit and the risk
      of harm. Trial participation may offer hope and social-emotional support and a
      strategy for coping with the emotional stress associated with advanced cancer and
      may, consequently, improve emotional well-being.

PMID- 23864289
TI  - Matched survival data in a co-twin control design.
AB  - When using the co-twin control design for analysis of event times, one needs a
      model to address the possible within-pair association. One such model is the
      shared frailty model in which the random frailty variable creates the desired
      within-pair association. Standard inference for this model requires independence
      between the random effect and the covariates. We study how violations of this
      assumption affect inference for the regression coefficients and conclude that
      substantial bias may occur. We propose an alternative way of making inference for
      the regression parameters by using a fixed-effects models for survival in matched
      pairs. Fitting this model to data generated from the frailty model provides
      consistent and asymptotically normal estimates of regression coefficients, no
      matter whether the independence assumption is met. 

PMID- 23864290
TI  - An introduction to comparative evolutionary psychology.
AB  - Previously we (Vonk and Shackelford, 2012, in press) proposed an integration of
      comparative psychology and evolutionary psychology into a new field of
      "comparative evolutionary psychology." This integrative discipline incorporates
      principles from ethology, ecology, biology, anthropology, and psychology, broadly
      defined. We present in this special issue a collection of original empirical and
      theoretical review articles in which leading researchers propose ways to
      successfully integrate comparative and evolutionary approaches within their
      particular areas of study. We showcase the key contributions of these articles
      and highlight several empirical and theoretical challenges, as well as key future
      directions, for comparative evolutionary psychology. 

PMID- 23864291
TI  - A framework for the comparative study of language.
AB  - Comparative studies of language are difficult because few language precursors are
      recognized. In this paper we propose a framework for designing experiments that
      test for structural and semantic patterns indicative of simple or complex
      grammars as originally described by Chomsky. We argue that a key issue is whether
      animals can recognize full recursion, which is the hallmark of context-free
      grammar. We discuss limitations of recent experiments that have attempted to
      address this issue, and point out that experiments aimed at detecting patterns
      that follow a Fibonacci series have advantages over other artificial context-free
      grammars. We also argue that experiments using complex sequences of behaviors
      could, in principle, provide evidence for fully recursive thought. Some of these
      ideas could also be approached using artificial life simulations, which have the
      potential to reveal the types of evolutionary transitions that could occur over
      time. Because the framework we propose has specific memory and computational
      requirements, future experiments could target candidate genes with the goal of
      revealing the genetic underpinnings of complex cognition. 

PMID- 23864292
TI  - Why offspring in nonhuman families differ.
AB  - Offspring within families, both human and nonhuman, often differ. The obvious
      question is: Why? Work on psychological differences on children within human
      families has focused primarily on differences in the nonshared environment of
      contemporary siblings, though the precise location of this nonshared environment
      is still the subject of much debate. Here I explore the range of explanations for
      within-brood diversity from the perspective of nonhuman families, particularly
      birds that share certain key features with human families. I examine the role of
      social rank in creating a nonshared environment within the family, and present
      data from a model system (an altricial bird) to illustrate how different the
      effective environments experienced by offspring sitting side-by-side in the same
      confined physical space, tended by the same parents, and experiencing similar
      ecological variability, can be. These broodmates can effectively live in
      different worlds. I then briefly explore other sources of diversity among
      offspring in nonhuman families, including within brood genetic differences and
      non-genetic maternal (parental) effects that often covary with birth / hatching
      rank. Given the ubiquity and far-reaching consequences of maternal effects in
      nonhuman families, and some human data suggestive of similar patterns, it would
      seem worthwhile to explore the potential role of maternal effects in creating
      phenotypic diversity in psychological traits among children in human families. 

PMID- 23864293
TI  - How can a multimodal approach to primate communication help us understand the
      evolution of communication?
AB  - Scientists studying the communication of non-human animals are often aiming to
      better understand the evolution of human communication, including human language.
      Some scientists take a phylogenetic perspective, where the goal is to trace the
      evolutionary history of communicative traits, while others take a functional
      perspective, where the goal is to understand the selection pressures underpinning
      specific traits. Both perspectives are necessary to fully understand the
      evolution of communication, but it is important to understand how the two
      perspectives differ and what they can and cannot tell us. Here, we suggest that
      integrating phylogenetic and functional questions can be fruitful in better
      understanding the evolution of communication. We also suggest that adopting a
      multimodal approach to communication might help to integrate phylogenetic and
      functional questions, and provide an interesting avenue for research into
      language evolution. 

PMID- 23864294
TI  - The origins of pedagogy: developmental and evolutionary perspectives.
AB  - The question of whether and how information is actively transferred from
      knowledgeable to ignorant individuals has received much attention in psychology
      and evolutionary biology. Research in these fields has proceeded largely
      independently, with studies of nonhuman animals focusing on knowledgeable
      individuals and whether or not they meet a functional definition of teaching,
      while studies of children focus on the learner's assumptions and inferences. We
      argue that a comprehensive theory of teaching will benefit from integrating
      perspectives and empirical phenomena from evolutionary and developmental
      disciplines. In this review, we identify cases of seemingly purposeful
      information transfer (i.e. teaching) in human and nonhuman animals, discuss what
      is known about the cognitive processes that support teaching in different
      species, and highlight ways in which each discipline might be informed by extant
      theories and empirical tools from the other. 

PMID- 23864295
TI  - Antipredatory behavior of zebrafish: adaptive function and a tool for
      translational research.
AB  - The zebrafish is gaining popularity in behavioral brain research. It may be a
      cost-effective tool with which we can improve our understanding of the biological
      and genetic mechanisms of human brain function and dysfunction. Some, myself and
      collaborators included, have argued that such translational relevance may be best
      achieved if one considers the ecology and species-specific characteristics of the
      study organism. In this review, I focus on our own studies investigating
      zebrafish fear responses, which may be utilized in analyzing the mechanisms of
      fear and anxiety, and which may be used for screening anxiolytic drugs. I review
      how zebrafish respond to their natural and synthetic alarm substance as well as
      to other fear-inducing stimuli, including sympatric and allopatric predatory
      fish, sympatric or allopatric harmless fish, moving (animated) images of
      predatory fish and moving images of abstract shapes. I discuss the behavioral
      responses these stimuli elicit, summarize the methods of the quantification of
      the behaviors, and speculate about their possible adaptive nature. Although we
      utilize complex visual stimuli and do not yet know what key features zebrafish
      may be sensitive to, our results, together with those published by others, imply
      that this simple vertebrate may have a bright future in behavioral brain
      research. 

PMID- 23864296
TI  - Comparative approaches to studying strategy: towards an evolutionary account of
      primate decision making.
AB  - How do primates, humans included, deal with novel problems that arise in
      interactions with other group members? Despite much research regarding how
      animals and humans solve social problems, few studies have utilized comparable
      procedures, outcomes, or measures across different species. Thus, it is difficult
      to piece together the evolution of decision making, including the roots from
      which human economic decision making emerged. Recently, a comparative body of
      decision making research has emerged, relying largely on the methodology of
      experimental economics in order to address these questions in a cross-species
      fashion. Experimental economics is an ideal method of inquiry for this approach.
      It is a well-developed method for distilling complex decision making involving
      multiple conspecifics whose decisions are contingent upon one another into a
      series of simple decision choices. This allows these decisions to be compared
      across species and contexts. In particular, our group has used this approach to
      investigate coordination in New World monkeys, Old World monkeys, and great apes
      (including humans), using identical methods. We find that in some cases there are
      remarkable continuities of outcome, as when some pairs in all species solved a
      coordination game, the Assurance game. On the other hand, we also find that these
      similarities in outcomes are likely driven by differences in underlying cognitive
      mechanisms. New World monkeys required exogenous information about their
      partners' choices in order to solve the task, indicating that they were using a
      matching strategy. Old World monkeys, on the other hand, solved the task without
      exogenous cues, leading to investigations into what mechanisms may be
      underpinning their responses (e.g., reward maximization, strategy formation,
      etc.). Great apes showed a strong experience effect, with cognitively enriched
      apes following what appears to be a strategy. Finally, humans were able to solve
      the task with or without exogenous cues. However, when given the chance to do so,
      they incorporated an additional mechanism unavailable to the other primates -
      language - to coordinate outcomes with their partner. We discuss how these
      results inform not only comparative psychology, but also evolutionary psychology,
      as they provide an understanding of the evolution of human economic behavior, and
      the evolution of decision making more broadly. 

PMID- 23864297
TI  - Are Clark's nutcrackers (Nucifraga columbiana) able to discriminate knowledge
      states of human experimenters during an object-choice task?
AB  - Corvids and primates have been shown to possess similar cognitive adaptations,
      yet these animals are seldom tested using similar procedures. Object-choice
      tasks, which have commonly been used to test whether an animal is able to infer
      the mental state of a human experimenter based on a gestural cue, provide one
      potential means of testing these animals using a similar paradigm. The current
      study used an object-choice task to examine whether the corvid, Clark's
      nutcracker (Nucifraga columbiana), is able to use a cognitive strategy to
      discriminate between the knowledge states of two human experimenters. One
      experimenter was informed, and the other uninformed, as to the location of a food
      reward hidden inside one of two opaque containers. During the Uninformed Gesture
      condition, the nutcrackers were given probe tests during which only the person
      performing as the uninformed experimenter provided a gesture. Thus, the
      nutcrackers could not use the experimenter's gesture to reliably find the food.
      During the Gesture Conflict condition, the nutcrackers were presented with a cue
      conflict. During probe tests, both the informed and the uninformed experimenter
      gestured to separate containers. Thus, to find the food the nutcrackers had to
      use the gesture from the informed experimenter and refrain from using the gesture
      of the uninformed experimenter. Our results showed that when the uninformed
      experimenter's gesture was presented alone, the birds continued to follow the
      gesture even though it was not consistently predictive of the food's location.
      However, when provided with two conflicting gestures, as a group the nutcrackers
      responded to the gesture of the informed experimenter at above chance levels.
      These results suggest that the birds had learned that the gesture was
      informative, perhaps by associative learning, yet when this mechanism was not
      reliable the nutcrackers were able to use either the human experimenters'
      presence/absence during the baiting process, or possibly their knowledge states,
      to determine which gesture to rely upon. 

PMID- 23864298
TI  - Toward a behavioral ecology of rescue behavior.
AB  - Although the study of helping behavior has revolutionized the field of behavioral
      ecology, scientific examination of rescue behavior remains extremely rare, except
      perhaps in ants, having been described as early as 1874. Nonetheless, recent work
      in our laboratories has revealed several new patterns of rescue behavior that
      appear to be much more complex than previously studied forms. This precisely
      directed rescue behavior bears a remarkable resemblance to what has been labeled
      empathy in rats, and thus raises numerous philosophical and theoretical
      questions: How should rescue behavior (or empathy) be defined? What distinguishes
      rescue from other forms of altruism? In what ways is rescue behavior in ants
      different from, and similar to, rescue in other non-human animals? What selection
      pressures dictate its appearance? In this paper, we review our own experimental
      studies of rescue in both laboratory and field, which, taken together, begin to
      reveal some of the behavioral ecological conditions that likely have given rise
      to rescue behavior in ants. Against this background, we also address important
      theoretical questions involving rescue, including those outlined above. In this
      way, we hope not only to encourage further experimental analysis of rescue
      behavior, but also to highlight important similarities and differences in very
      distant taxa. 

PMID- 23864299
TI  - When violence pays: a cost-benefit analysis of aggressive behavior in animals and
      humans.
AB  - An optimization analysis of human behavior from a comparative perspective can
      improve our understanding of the adaptiveness of human nature. Intra-specific
      competition for resources provides the main selective pressure for the evolution
      of violent aggression toward conspecifics, and variation in the fitness benefits
      and costs of aggression can account for inter-specific and inter-individual
      differences in aggressiveness. When aggression reflects competition for
      resources, its benefits vary in relation to the characteristics of the resources
      (their intrinsic value, abundance, spatial distribution, and controllability)
      while its costs vary in relation to the characteristics of organisms and how they
      fight (which, in turn, affects the extent to which aggression entails risk of
      physical injury or death, energetic depletion, exposure to predation,
      psychological and physiological stress, or damage to social relationships).
      Humans are a highly aggressive species in comparison to other animals, probably
      as a result of an unusually high benefit-to-cost ratio for intra-specific
      aggression. This conclusion is supported by frequent and widespread occurrence of
      male-male coalitionary killing and by male-female sexual coercion. Sex
      differences in violent aggression in humans and other species probably evolved by
      sexual selection and reflect different optimal competitive strategies for males
      and females. 

PMID- 23864300
TI  - Does fertility status influence impulsivity and risk taking in human females?
      Adaptive influences on intertemporal choice and risky decision making.
AB  - Informed by the research on adaptive decision making in other animal species,
      this study investigated human females' intertemporal and risky choices across the
      ovulatory cycle. We tested the hypothesis that at peak fertility, women who are
      exposed to environments that signal availability of higher quality mates (by
      viewing images of attractive males), become more impulsive and risk-seeking in
      economic decision tasks. To test this, we collected intertemporal and risky
      choice measures before and after exposure to images of either attractive males or
      neutral landscapes both at peak and low fertility conditions. The results showed
      an interaction between women's fertility status and image type, such that women
      at peak fertility viewing images of attractive men chose the smaller, sooner
      monetary reward option less than women at peak fertility viewing neutral images.
      Neither fertility status nor image type influenced risky choice. Thus, though
      exposure to images of men altered intertemporal choices at peak fertility, this
      occurred in the opposite direction than predicted--i.e., women at peak fertility
      became less impulsive. Nevertheless, the results of the current study provide
      evidence for shifts in preferences over the ovulatory cycle and opens future
      research on economic decision making.

PMID- 23864301
TI  - Psychobehavioral effects of hormonal contraceptive use.
AB  - Although female use of hormonal contraceptives (HCs) has been associated with a
      variety of physical side effects, the psychological and behavioral side effects
      have received comparatively little attention until recently. Indeed, the long
      term impact of HC use on human psychology has been vastly under-researched and
      has only recently become a focus for mainstream scholars. Women who use HCs
      report higher rates of depression, reduced sexual functioning, and higher
      interest in short-term sexual relationships compared to their naturally-cycling
      counterparts. Also, HC use may alter women's ability to attract a mate, as well
      as the mate retention behaviors in both users and their romantic partners. Some
      evidence even suggests that HC use alters mate choice and may negatively affect
      sexual satisfaction in parous women, with potential effects on future offspring.
      Interestingly, HCs have become a standard method of population control for
      captive nonhuman primates, opening up exciting avenues for potential comparative
      research. Here, the existing literature on the psychobehavioral effects of HCs in
      humans and nonhuman primates is reviewed and discussed. The potential resulting
      downstream consequences for the path of human evolution and recommendations for
      how future research could tease apart the underlying causes of these
      psychobehavioral effects of HC use are discussed, including suggestions for
      research involving nonhuman primates. 

PMID- 23864302
TI  - The biological roots of aesthetics and art.
AB  - Animals' choice behavior is driven by motivation that is attributable to both
      innate urges and from positive and negative reinforcements. Using a comparative
      approach as well as experimental evidence, I explore how the first involves
      fitness-enhancing benefits from aesthetics that are derived from ancestral
      choices via natural selection. Innate urges and aesthetics help guide animals to
      produce appropriate positive and negative choices that are species-specific.
      Choices of food, habitat and mates or associates are considered. I propose that
      art is not a uniquely human product, but a representation or an extension of the
      maker, as are the ornaments, displays, and songs of a bird. 

PMID- 23864303
TI  - The Janus-faced nature of comparative psychology--strength or weakness?
AB  - What is the nature of comparative psychology and how does or should it relate to
      evolutionary psychology? This is a time of reassessment of both fields and this
      article reviews the history of comparative psychology and its relationships with
      evolutionary psychology, ethology, and other approaches to behavior from the
      perspective of a former editor of the Journal of Comparative Psychology who has
      spent many decades engaged in research in animal behavior. Special attention is
      given to a reassessment of comparative psychology that was carried out in 1987.
      The various tensions and orientations that seem endemic to comparative psychology
      may, in fact, be both a strength and weakness as comparative psychology and
      evolutionary approaches to human psychology return to issues prominent in the
      late 19th Century, when both fields were just becoming established. 

PMID- 23864304
TI  - [The Somatic Symptoms Experiences Questionnaire (SSEQ): a new self-report
      instrument for the assessment of psychological characteristics of patients with
      somatoform disorder].
AB  - Psychological symptoms of somatoform disorders will be part of their new
      definition in DSM-5. We developed the Somatic Symptoms Experiences Questionnaire
      (SSEQ) as a self-report questionnaire to assess important psychological
      characteristics of patients with somatoform disorders. Item selection and
      identification of factor structure, as well as reliability and validity have been
      checked in a sample of N=453 psychsomatic outpatients. Results of a principal
      components analysis with Promax-rotation suggested 4 factors (health worries,
      illness experience, difficulties in interaction with doctors, impact of illness).
      Validity analyses confirmed associations between the SSEQ-Scores and the physical
      disability of patients. Although further assessments of psychometric qualities
      are needed, the questionnaire appears to be well-suited for future assessment of
      relevant psychological features of somatoform disorders. 

PMID- 23864305
TI  - Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE
      enables shortening of renoprotective amino acid infusion.
AB  - PURPOSE: The aim of the study was to investigate the feasibility of shortening
      the recommended 4-h renoprotective amino acid infusion in patients receiving
      peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5
      fluorouracil. We evaluated the clearance of radiopeptide from the blood, long
      term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino
      acid infusion and renal uptake in patients receiving an abbreviated infusion.
      METHODS: The whole-blood clearance of (177)Lu-DOTA-octreotate (LuTate) was
      measured in 13 patients receiving PRCRT. A retrospective analysis of short-term
      and long-term changes in glomerular filtration rate (GFR) in 96 consecutive
      patients receiving a 4-h infusion was performed. Renal LuTate retention estimated
      using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid
      infusion was compared with that in 72 cycles with the 4-h infusion. RESULTS:
      LuTate demonstrated biexponential blood clearance with an initial clearance half
      time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With
      the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean
      increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4
      nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after
      a median follow up of 22 months was 2.2 ml/min per year. There was no significant
      difference in the renal LuTate retention measured in patients receiving a 2.5-h
      amino acid infusion compared to those who had a 4-h infusion. CONCLUSION: The
      greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h
      after injection. This, combined with the safety of LuTate PRCRT, allows
      consideration of an abbreviated amino acid infusion, increasing patient
      convenience and reducing human resource allocation.

PMID- 23864306
TI  - Resident education in the era of patient safety: a nationwide analysis of
      outcomes and complications in resident-assisted oncologic surgery.
AB  - BACKGROUND: Complex, oncologic surgery is an important component of resident
      education. Our objective was to evaluate the impact of resident participation in
      oncologic procedures on overall 30-day morbidity and mortality. METHODS: A
      retrospective cohort analysis was performed using the National Surgical Quality
      Improvement Program Participant User Files for 2005-2009. Colorectal,
      hepatopancreaticobiliary, and gastroesophageal oncology procedures were included.
      Multivariate logistic regression was used to assess the impact of trainee
      involvement on 30-day morbidity and mortality after adjusting for potential
      confounders. RESULTS: A total of 77,862 patients were included for analysis,
      53,885 (69.2%) involving surgical trainees and 23,977 (30.8%) without trainees.
      The overall 30-day morbidity was significantly higher in the trainee group [27.2
      vs. 21%, adjusted odds ratio (AOR) 1.19, 95% confidence interval (CI) 1.15-1.24,
      p < 0.0001)]; however, there was significantly lower 30-day postoperative
      mortality in the trainee group (1.9 vs. 2.1%, AOR 0.87, 95% CI 0.77-0.98, p =
      0.02) and significantly lower failure-to-rescue rate (defined as mortality rate
      among patients suffering one or more postoperative complications) (5.9 vs. 7.6%,
      AOR 0.79, 95% CI 0.68-0.90, p = 0.001). The overall 30-day morbidity was highest
      in the PGY 5 level (29%) compared to 24% for PGY 1 or 2 and 23% for PGY 3 (AOR
      per level increase 1.05, 95% CI 1.03-1.07, p < 0.0001). CONCLUSIONS: Trainee
      participation in complex, oncologic surgery is associated with significantly
      higher rates of 30-day postoperative complications in NSQIP-participating
      hospitals; however, this effect is countered by overall lower 30-day mortality
      and improved rescue rate in preventing death among patients suffering
      complications.

PMID- 23864308
TI  - KRAS mutations and rectal cancer response to chemoradiation: are we closer to
      personalization of therapy?

PMID- 23864307
TI  - miR-675 mediates downregulation of Twist1 and Rb in AFP-secreting hepatocellular
      carcinoma.
AB  - BACKGROUND: Alpha-fetoprotein (AFP)-secreting hepatocellular carcinomas (HCC)
      represent a genetically distinct subset of tumors often associated with a worse
      prognosis. However, the molecular mechanisms that underlie these phenotypic
      differences remain poorly understood. METHODS: HCC tumor samples from 27 patients
      were profiled using the Affymetrix 133 Plus 2.0 GeneChips. GeneGO Metacore
      software was used to identify altered biologic pathways. Expression validation
      was confirmed by RT-PCR. Manipulation of miR-675 by overexpression and antagomir
      mediated knockdown was carried out with subsequent evaluation of effects on cell
      behavior by cell cycle, proliferation, invasion, and growth in soft agar assays.
      RESULTS: We identified a strong relationship between primary tumor H19 gene
      expression and elevated serum AFP. H19 has recently been identified to encode
      microRNA-675 (miR-675), and we confirmed the relationship in an independent
      sample of patients. Pathway analyses of the effect of miR-675 overexpression in
      hepatoma cells revealed a predominant upregulation of cell adhesion and cell
      cycle initiation pathways. We have demonstrated that miR-675 mediates increases
      in proliferation and an accumulation of cells with tetraploid DNA content
      associated with a repression of Rb. We also demonstrated that overexpression of
      miR-675 alters cellular morphology, reduces invasive potential, and increases
      anchorage-independent growth capacity. These findings are consistent with a
      mesenchymal-to-epithelial transition, associated with a reduction in the
      expression of the key EMT mediator, Twist1. CONCLUSIONS: Expression of the miR
      675 in hepatocellular carcinoma links a dramatic upregulation of proliferative
      and growth capacity with inhibition of motility in HCC cells.

PMID- 23864309
TI  - Robotic versus laparoscopic adrenalectomy for pheochromocytoma.
AB  - BACKGROUND: Although initial reports demonstrated the safety and feasibility of
      robotic adrenalectomy (RA), there are scant data on the use of this approach for
      pheochromocytoma. The aim of this study is to compare perioperative outcomes and
      efficacy of RA versus laparoscopic adrenalectomy (LA) for pheochromocytoma.
      METHODS: Within 3 years, 25 patients underwent 26 RA procedures for
      pheochromocytoma. These patients were compared with 40 patients who underwent 42
      LA procedures before the start of the robotic program. Data were retrospectively
      reviewed from a prospectively maintained, IRB-approved adrenal database. RESULTS:
      Demographic and clinical parameters at presentation were similar between the
      groups, except for a larger tumor size in the robotic group. In both groups, skin
      to-skin operative time, estimated blood loss less, and intraoperative hemodynamic
      parameters were similar. The conversion to open rate was 3.9 % in the robotic and
      7.5 % in the laparoscopic group (p = .532). There was no morbidity or mortality
      in the robotic group; morbidity was 10 % (p = .041) and mortality 2.5 % in the
      laparoscopic group. The pain score on postoperative day 1 was lower, and the
      length of hospital stay shorter in the robotic group (1.2 +/- .1 vs. 1.7 +/- .1
      days, p = .036). CONCLUSIONS: To our knowledge, this is the first study comparing
      robotic versus laparoscopic resection of pheochromocytoma. Our results show that
      the robotic approach is similar to the laparoscopic regarding safety and
      efficacy. The lower morbidity, less immediate postoperative pain, and shorter
      hospital stay observed in the robotic approach warrant further investigation in
      future larger studies.

PMID- 23864310
TI  - An index to identify stroke-related vs incidental patent foramen ovale in
      cryptogenic stroke.
AB  - OBJECTIVE: We aimed to create an index to stratify cryptogenic stroke (CS)
      patients with patent foramen ovale (PFO) by their likelihood that the stroke was
      related to their PFO. METHODS: Using data from 12 component studies, we used
      generalized linear mixed models to predict the presence of PFO among patients
      with CS, and derive a simple index to stratify patients with CS. We estimated the
      stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA
      recurrence rates. RESULTS: Variables associated with a PFO in CS patients
      included younger age, the presence of a cortical stroke on neuroimaging, and the
      absence of these factors: diabetes, hypertension, smoking, and prior stroke or
      TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these
      variables so that the youngest patients with superficial strokes and without
      vascular risk factors have the highest score. PFO prevalence increased from 23%
      (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95%
      CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction
      estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year
      recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of
      Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest.
      CONCLUSION: Clinical characteristics identify CS patients who vary markedly in
      PFO prevalence, reflecting clinically important variation in the probability that
      a discovered PFO is likely to be stroke-related vs incidental. Patients in strata
      more likely to have stroke-related PFOs have lower recurrence risk.

PMID- 23864311
TI  - Contribution of cortical lesion subtypes at 7T MRI to physical and cognitive
      performance in MS.
AB  - OBJECTIVES: Evaluate cross-sectionally the contribution of focal cortical lesion
      (CL) subtypes at ultra-high-field MRI and traditional MRI metrics of brain damage
      to neurologic disability and cognitive performance in a heterogeneous multiple
      sclerosis (MS) cohort. METHODS: Thirty-four patients with early or established
      disease including clinically isolated syndrome, relapsing-remitting MS, and
      secondary progressive MS were scanned on a human 7-tesla (7T) (Siemens) scanner
      to acquire fast low-angle shot (FLASH) T2*-weighted images for characterization
      of white matter and deep gray matter lesion volume, and CL types. Patients also
      underwent anatomical 3T MRI for cortical thickness estimation, and
      neuropsychological testing within 1 week of the 7T scan. Twenty-seven patient
      scans were acceptable for further analysis. Neurologic disability was measured
      using the Expanded Disability Status Scale. RESULTS: Type III-IV CLs had the
      strongest relationship to physical disability (rho = 0.670, p < 0.0001). White
      matter lesion volume and type I CLs are each significantly associated with 6 of
      11 neuropsychological test variables. Type III-IV CLs significantly correlate
      with 4 of 11 neuropsychological test variables whereas type II CLs, deep gray
      matter lesion volume, and cortical thickness metrics are less frequently
      associated with cognitive performance. CONCLUSIONS: Leukocortical (type I) and
      subpial (III-IV) CLs identified on 7T FLASH-T2* sequences are potential cortical
      biomarkers of cognitive and neurologic status in MS.

PMID- 23864312
TI  - Head impulses in complete bilateral vestibular loss: catch-up saccades require
      visual input.

PMID- 23864313
TI  - Toward a better understanding of PFO and stroke risk.

PMID- 23864314
TI  - Central pain modulation after subthalamic nucleus stimulation: A crossover
      randomized trial.
AB  - OBJECTIVE: To investigate the acute effect of subthalamic nuclei deep brain
      stimulation (STN-DBS) and levodopa on pain and tolerance thresholds in patients
      with Parkinson disease. We hypothesized that a modification of pain threshold
      after STN-DBS would suggest a central modification of pain perception, whereas
      the absence of pain threshold change after STN-DBS would correspond to a
      peripheral mechanism via a decrease of painful stimuli. METHODS: Nineteen
      patients with Parkinson disease were included in this double-blind, randomized,
      crossover study. Postoperatively, we evaluated pain thresholds (thermal and
      mechanical) and motor symptoms under 3 acute conditions: stimulation
      on/medication off; stimulation off/medication on; and stimulation off/medication
      off. We also conducted a retrospective analysis of the data prospectively
      recorded during the follow-up of the cohort pre- and postoperatively (Unified
      Parkinson's Disease Rating Scale [UPDRS] score, Hoehn and Yahr stage, equivalent
      levodopa daily dose, and tapping test score). RESULTS: We found a significant
      increase of pain and tolerance mechanical thresholds not only after acute STN-DBS
      but also after acute levodopa administration. We did not find any significant
      correlation between postoperative clinical pain improvement and UPDRS-III
      improvement after acute levodopa or STN-DBS, nor with motor complications
      improvement assessed with UPDRS-IV after chronic STN-DBS. No correlation was
      found between postoperative clinical pain improvement and mechanical pain
      threshold modification. CONCLUSION: Clinical pain alleviation after STN-DBS
      cannot be considered merely as a consequence of motor complications improvement
      and could be attributable to a direct central modulation of pain perception, via
      increased mechanical pain and tolerance thresholds.

PMID- 23864315
TI  - Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid
      angiopathy.
AB  - OBJECTIVE: We investigated the prevalence and clinical-radiologic associations of
      cortical superficial siderosis (cSS) in patients with probable cerebral amyloid
      angiopathy (CAA) compared to those with intracerebral hemorrhage (ICH) not
      attributed to CAA. METHODS: We conducted a retrospective multicenter cohort study
      of 120 patients with probable CAA and 2 comparison groups: 67 patients with
      either single lobar ICH or mixed (deep and lobar) hemorrhages; and 22 patients
      with strictly deep hemorrhages. We rated cSS, ICH, white matter changes, and
      cerebral microbleeds. RESULTS: cSS was detected in 48 of 120 (40%; 95% confidence
      interval [CI]: 31.2%-49.3%) patients with probable CAA, 10 of 67 (14.9%; 95% CI:
      7.4%-25.7%) with single lobar ICH or mixed hemorrhages, and 1 of 22 (4.6%; 95%
      CI: 0.1%-22.8%) patients with strictly deep hemorrhages (p < 0.001 for trend).
      Disseminated cSS was present in 29 of 120 (24%; 95% CI: 16.8%-32.8%) patients
      with probable CAA, but none of the other patients with ICH (p < 0.001). In
      probable CAA, age (odds ratio [OR]: 1.09; 95% CI: 1.03-1.15; p = 0.002), chronic
      lobar ICH (OR: 3.94; 95% CI: 1.54-10.08; p = 0.004), and a history of transient
      focal neurologic episodes (OR: 11.08; 95% CI: 3.49-35.19; p < 0.001) were
      independently associated with cSS. However, cSS occurred in 17 of 48 patients
      with probable CAA (35.4%; 95% CI: 22.2%-50.5%) without chronic lobar ICH.
      CONCLUSIONS: cSS (particularly if disseminated) is a common and characteristic
      feature of CAA. Chronic lobar ICH is an independent risk factor for cSS, but the
      causal direction and mechanism of association are uncertain. Hemorrhage into the
      subarachnoid space, independent of previous (chronic) lobar ICH, must also
      contribute to cSS in CAA. Transient focal neurologic episodes are the strongest
      clinical marker of cSS.

PMID- 23864316
TI  - Networks underlying paroxysmal fast activity and slow spike and wave in Lennox
      Gastaut syndrome.
AB  - OBJECTIVE: To use EEG-fMRI to determine which structures are critically involved
      in the generation of paroxysmal fast activity (PFA) and slow spike and wave (SSW)
      (1.5-2.5 Hz), the characteristic interictal discharges of Lennox-Gastaut syndrome
      (LGS). METHODS: We studied 13 well-characterized patients with LGS using
      structural imaging and EEG-fMRI at 3 tesla. Ten patients had cortical structural
      abnormalities. PFA and SSW were considered as separate events in the fMRI
      analysis. RESULTS: Simultaneous with fMRI, PFA was recorded in 6 patients and SSW
      in 9 (in 2, both were recorded). PFA events showed almost uniform increases in
      blood oxygen level-dependent (BOLD) signal in "association" cortical areas, as
      well as brainstem, basal ganglia, and thalamus. SSW showed a different pattern of
      BOLD signal change with many areas of decreased BOLD signal, mostly in primary
      cortical areas. Two patients with prior callosotomy had lateralized as well as
      generalized PFA. The lateralized PFA was associated with a hemispheric version of
      the PFA pattern we report here. CONCLUSION: PFA is associated with activity in a
      diffuse network that includes association cortices as well as an unusual pattern
      of simultaneous activation of subcortical structures (brainstem, thalamus, and
      basal ganglia). By comparison, the SSW pattern is quite different, with cortical
      and subcortical activations and deactivations. Regardless of etiology, it appears
      that 2 key, but distinct, patterns of diffuse brain network involvement
      contribute to the defining electrophysiologic features of LGS.

PMID- 23864318
TI  - Rare cerebellar lesions in a carbon monoxide poisoning case.

PMID- 23864317
TI  - Expression of Bmi1, FoxF1, Nanog, and gamma-catenin in relation to hedgehog
      signaling pathway in human non-small-cell lung cancer.
AB  - BACKGROUND: Hedgehog signaling is known to be involved in both lung organogenesis
      and lung carcinogenesis. The aim of this study was to examine potential
      downstream targets of the hedgehog signaling pathway in non-small-cell lung
      cancer. METHODS: Protein expression of Bmi1, FoxF1, Nanog, and gamma-catenin was
      examined by immunohistochemistry in 80 non-small-cell lung cancer samples.
      Correlations with the previously immunohistochemically recovered results for
      sonic hedgehog, Ptch1, Smo, Gli1, and Gli2 in the same cohort of tumors as well
      as the clinicopathological characteristics of the tumors were also evaluated.
      RESULTS: Bmi1 was expressed in 78/80 (97.5 %) cases of non-small-cell lung cancer
      and correlated with male gender and expression of Gli1. Positive expression of
      FoxF1 was found in 62/80 (77.5 %) cases. Expression of FoxF1 correlated with
      lymph node metastases, Bmi1, and hedgehog pathway activation. Overexpression of
      Nanog was also noted in 74/80 (92.5 %) tumors and correlated with Bmi1.
      Cytoplasmic accumulation of gamma-catenin was observed in 85 % (68/80) of the
      tumors and correlated with the expression of Bmi1, FoxF1, and Nanog. CONCLUSION:
      Several developmental pathways seem to be implicated in non-small-cell lung
      cancer. It is also suggested that Bmi1 and FoxF1 may cooperate with hedgehog
      signaling in non-small-cell lung carcinogenesis.

PMID- 23864320
TI  - [Unequal social participation in later life].
AB  - The concept of active ageing comprises the maintenance of societal participation
      throughout the life span into old age. "Good" ageing in line with this activity
      paradigm develops into a starting point of social inequality rather than being
      its result. Based on the German Ageing Survey (DEAS) we investigated access to
      volunteering and to educational activities depending on social and spatial
      aspects of inequality. Societal participation is socially and spatially
      structured. Individuals from a lower social class are less often involved in
      educational activities or in volunteering. Moreover, individuals living in
      economically disadvantaged regions are less likely to participate than in
      economically strong regions. Disadvantages cumulate if low individual resources
      overlap with poor economic conditions in the living area. Measures to facilitate
      participation should be taken on the local level to enhance opportunities for
      volunteering and educational activities. This should help to sustainably increase
      the participation of individuals from lower social classes.

PMID- 23864319
TI  - [Diabetes and osteoporosis: pathophysiological interactions and clinical
      importance for geriatric patients].
AB  - Osteoporosis is an age-associated disease, resulting in impaired bone quality and
      increased risk for bone fractures. Patients with type 2 diabetes mellitus have-
      despite a normal or even increased bone mineral density--an increased risk for
      fractures, which is related to an imbalance between osteoblastic bone formation
      and osteoclastic resorption. Complex pathophysiological mechanisms associated
      with insulin resistance and hyperglycemia are involved in the deleterious effects
      on osteoblast function and bone formation. The quality and regimen of
      antidiabetic therapy are discussed as modulators of bone metabolism. Of great
      clinical importance is an assessment of the fall risk especially for diabetic
      patients, because late complications, such as neuropathy, but also side effects
      of medication can result in a significantly increased risk for falls. Lifestyle
      intervention is of advantage with respect to diabetes and osteoporosis prevention
      and therapy. Vitamin D supplementation results in favorable effects with a
      reduced risk for falls and also improvements of insulin sensitivity. According to
      published data, the safety and efficacy of specific medication for the treatment
      of osteoporosis (bisphosphonates, denosumab, selective estrogen receptor
      modulators) reveal no difference between patients with and without diabetes
      mellitus.

PMID- 23864322
TI  - [Geriatric Rehabilitation: a model with no future].

PMID- 23864327
TI  - Myoferlin is a key regulator of EGFR activity in breast cancer.
AB  - Myoferlin is a member of the ferlin family of proteins that participate in plasma
      membrane fusion, repair, and endocytosis. While some reports have implicated
      myoferlin in cancer, the extent of its expression in and contributions to cancer
      are not well established. In this study, we show that myoferlin is overexpressed
      in human breast cancers and that it has a critical role in controlling
      degradation of the epidermal growth factor (EGF) receptor (EGFR) after its
      activation and internalization in breast cancer cells. Myoferlin depletion
      blocked EGF-induced cell migration and epithelial-to-mesenchymal transition. Both
      effects were induced as a result of impaired degradation of phosphorylated EGFR
      via dysfunctional plasma membrane caveolae and alteration of caveolin homo
      oligomerization. In parallel, myoferlin depletion reduced tumor development in a
      chicken chorioallantoic membrane xenograft model of human breast cancer.
      Considering the therapeutic significance of EGFR targeting, our findings identify
      myoferlin as a novel candidate function to target for future drug development.

PMID- 23864328
TI  - Prognostic values of initial responses to low-dose (131)I-MIBG therapy in
      patients with malignant pheochromocytoma and paraganglioma.
AB  - PURPOSE: We retrospectively examined whether or not initial responses of first
      low-dose (131)I-meta-iodo-benzyl-guanidine radiotherapy ((131)I-MIBG therapy) in
      patients with malignant pheochromocytoma and paraganglioma had prognostic values.
      MATERIALS AND METHODS: This study included 26 patients with malignant
      pheochromocytoma (n = 18) and paraganglioma (n = 8) who underwent the first
      (131)I-MIBG therapy between October 2001 and September 2007. Based on the initial
      subjective, hormonal, scintigraphic, and objective responses to (131)I-MIBG
      therapy, the responses were divided into progression disease (PD) and non-PD. We
      examined the following factors for prognostic significance: sex, age, disease,
      initial diagnosis (benign or malignant pheochromocytoma), hypertension, diabetes
      mellitus, palpitations, symptoms related to bone metastases, and number of low
      dose (131)I-MIBG therapy. Univariate Cox proportional regression analysis was
      used to identify prognostic factors for overall survival. Overall survival was
      analyzed by Kaplan-Meier method and the curves were compared using the log-rank
      test. RESULTS: The median survival time was 56 months. In the follow-up period,
      16 patients died from exacerbation of their diseases. Univariate analysis showed
      that the hormonal PD [hazard ratio (HR) 3.20, P = 0.034, confidence interval (CI)
      1.09-9.93], objective PD (HR 11.89, P = 0.0068, CI 2.14-65.85), single-time
      (131)I-MIBG therapy (HR 3.22, P = 0.020, CI 1.21-8.79), hypertension (HR 2.93, P
      = 0.044, CI 1.02-10.50), and symptoms related to bone metastases (HR 3.54, P =
      0.023, CI 1.18-13.04) were bad prognostic factors for overall survival. Kaplan
      Meier analysis demonstrated that the hormonal non-PD (P = 0.026), objective non
      PD (P = 0.0002), multiple-time (131)I-MIBG therapy (P = 0.013), and no symptom
      related to bone metastases (P = 0.024) were significantly associated with good
      prognosis. Overall survival rate was 70 and 50 % at 5 years from the initial
      diagnosis and from the first (131)I-MIBG therapy, respectively. CONCLUSION: The
      hormonal and objective responses to the first low-dose (131)I-MIBG therapy as
      well as complication of hypertension and symptoms related to bone metastases may
      be prognostic factors in patients with malignant pheochromocytoma and
      paraganglioma.

PMID- 23864329
TI  - Biochemical evidence that human EB1 does not bind preferentially to the
      microtubule seam.
AB  - EB1 is a highly conserved microtubule (MT) plus end tracking protein (+TIP)
      involved in regulating MT dynamics, but the mechanisms of its effects on MT
      polymerization remain undefined. Resolving this question requires understanding
      how EB1 interacts with MTs. Previous electron microscopy of the S. pombe EB1
      homolog Mal3p suggested that Mal3p binds specifically to the MT seam, implying
      that EB1 family members promote MT polymerization by stabilizing the seam.
      However, more recent electron microscopy indicates that Mal3p binds everywhere
      except the seam. Neither set of experiments investigated the behavior of human
      EB1, or provided an explanation for why these studies arrived at different
      answers. To resolve these questions, we have used a combination of MT-binding
      assays and theoretical modeling with MTBindingSim. Our results indicate that
      human EB1 binds to the lattice, consistent with the recent Mal3p results, and
      show that Mal3p-binding assays that were previously interpreted as evidence for
      preferential seam binding are equally consistent with weak lattice binding. In
      addition, we used analytical ultracentrifugation to investigate the possibility
      that the EB1 monomer-dimer equilibrium might contribute to EB1 binding behavior,
      and determined that the EB1 dimerization dissociation constant is approximately
      90 nM. We and others find that the cellular concentration of EB1 is on the order
      of 200 nM, suggesting that a portion of EB1 may be monomeric at physiological
      concentrations. These observations lead us to suggest that regulation of EB1
      dimerization might play a role in controlling EB1 function.

PMID- 23864331
TI  - Clear cell renal cell carcinoma and papillary renal cell carcinoma:
      differentiation of distinct histological types with multiphase CT.
AB  - PURPOSE: Conventional clear cell renal cell carcinoma (ccRCC) and papillary renal
      cell carcinoma (pRCC) have different behavioral characteristics and clinical
      management strategies (nephrectomy vs. nephron-sparing surgery). Our aim was to
      retrospectively evaluate the contrast enhancement pattern of ccRCC and pRCC and
      evaluate its possible diagnostic role for preoperative differentiation using a
      standardized protocol. MATERIALS AND METHODS: Quadriphasic multidetector computed
      tomography (CT) images (unenhanced, corticomedullary, nephrographic, and
      excretory phases) of 19 patients with 20 ccRCC and 14 patients with 15 pRCC
      lesions (mean ages, 62.3+/-14.1 and 61.4+/-13.7 years, respectively) were
      reviewed retrospectively. The attenuation characteristics were compared with the
      attenuation of the normal renal cortex using either multiple 10 mm2 regions of
      interest or whole tumor attenuation measurements. The degree of contrast
      enhancement was also compared. RESULTS: Univariate analysis revealed that ccRCC
      lesions showed higher mean attenuation values on the corticomedullary and
      nephrographic phases compared with pRCC masses (P < 0.05) using both measurement
      techniques. CONCLUSION: The findings underscore the importance of multiphase CT
      in the differentiation of these two subtypes of RCC using standard assessment
      techniques. The measurement of the degree of enhancement on contrast-enhanced
      multidetector CT may be a simple and useful method to radiologically
      differentiate between the two histological types of RCC.

PMID- 23864330
TI  - IL-12Rbeta1 deficiency: mutation update and description of the IL12RB1 variation
      database.
AB  - IL-12Rbeta1 deficiency is an autosomal recessive disorder characterized by
      predisposition to recurrent and/or severe infections caused by otherwise poorly
      pathogenic mycobacteria and salmonella. IL-12Rbeta1 is a receptor chain of both
      the IL-12 and the IL-23 receptor and deficiency of IL-12Rbeta1 thus abolishes
      both IL-12 and IL-23 signaling. IL-12Rbeta1 deficiency is caused by bi-allelic
      mutations in the IL12RB1 gene. Mutations resulting in premature stop codons, such
      as nonsense, frame shift, and splice site mutations, represent the majority of IL
      12Rbeta1 deficiency causing mutations (66%; 46/70). Also every other morbid
      mutation completely inactivates the IL-12Rbeta1 protein. In addition to disease
      causing mutations, rare and common variations with unknown functional effect have
      been reported in IL12RB1. All these variants have been deposited in the online
      IL12RB1 variation database (www.LOVD.nl/IL12RB1). In this article, we review the
      function of IL-12Rbeta1 and molecular genetics of human IL12RB1. 

PMID- 23864332
TI  - Clinical and radiologic manifestations of pulmonary cryptococcosis in
      immunocompetent patients and their outcomes after treatment.
AB  - PURPOSE: We aimed to investigate clinical and radiologic manifestations of
      pulmonary cryptococcosis in immunocompetent patients and their outcomes after
      treatment. MATERIALS AND METHODS: We retrospectively reviewed the medical
      records, initial and follow-up chest computed tomography scans and/or radiographs
      for initial clinical and radiologic manifestations and outcomes following
      antifungal treatment of 12 immunocompetent patients diagnosed with pulmonary
      cryptococcosis between 1990 and 2012. RESULTS: Twelve patients (age range, 21-62
      years; males, eight patients [66.7%]) were included. Nine (75%) patients were
      symptomatic, eight of whom had disseminated infection with central nervous system
      involvement. Initial pulmonary abnormalities consisted of single nodules/masses
      (n=5), single segmental or lobar mass-like consolidation (n=3), multiple cavitary
      and noncavitary nodules (n=1), and multifocal consolidation plus nodules (n=3).
      These lesions ranged from less than 1 cm to 15 cm in greatest diameter. Distinct
      subpleural and lower lung predominance was observed. Seven patients (58.3%) had
      one or more atypical/aggressive findings, namely endobronchial obstruction (n=4),
      calcified (n=1) or enlarged (n=4) mediastinal/hilar lymph nodes, vascular
      compression (n=1), pericardial involvement (n=1), and pleural involvement (n=2).
      Following antifungal therapy, radiologic resolution was variable within the first
      six months of eight nonsurgical cases. Substantial (>75%) improvement with some
      residual abnormalities, bronchiectasis, cavitation, and/or fibrotic changes were
      frequently observed after 12-24 months of treatment (n=6). CONCLUSION: Pulmonary
      cryptococcosis in immunocompetent patients frequently causes disseminated
      infection with atypical/aggressive radiologic findings that are gradually and/or
      incompletely resolved after treatment. The presence of nonenhanced low
      attenuation areas within subpleural consolidation or mass and the absence of tree
      in-bud appearance should raise concern for pulmonary cryptococcosis, particularly
      in patients presenting with meningitis.

PMID- 23864333
TI  - Transcriptional regulation of mouse mesencephalic astrocyte-derived neurotrophic
      factor in Neuro2a cells.
AB  - Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel type of
      trophic factor. Recent studies indicate that the MANF gene is induced in response
      to endoplasmic reticulum (ER) stress through ER stress response element II (ERSE
      II) in its 5'-flanking region. In this study, we evaluated the roles of six ER
      stress response transcription factors in the regulation of the promoter
      activities of the mouse MANF gene via ERSE-II using various types of mutant MANF
      luciferase reporter constructs. Treatment with thapsigargin (Tg) induced MANF
      mRNA generation in parallel with the elevation of ATF6alpha, sXBP and Luman mRNA
      levels in Neuro2a cells. Of the six transcription factors, ATF6beta most strongly
      increased the MANF promoter activity via ERSE-II, while the effects of ATF6beta
      and sXBP1 were moderate. However, overexpression of Luman or OASIS did not
      enhance ERSE-II-dependent MANF promoter activity in Neuro2a cells. To evaluate
      the relationships between transcription factors in the regulation of ERSE-II
      dependent MANF promoter activity, we transfected two effective transcription
      factor constructs chosen from ATF6alpha, ATF6beta, uXBP1 and sXBP1 into Neuro2a
      cells with the MANF reporter construct. The MANF promoter activity induced by co
      transfection of ATF6alpha with ATF6beta was significantly lower than that induced
      by ATF6alpha alone, while other combinations did not show any effect on the ERSE
      II-dependent MANF promoter activity in Neuro2a cells. Our study is the first to
      show the efficiency of ER stress-related transcription factors for ERSE-II in
      activating the transcription of the mouse MANF gene in Neuro2a cells. 

PMID- 23864334
TI  - Identification of microRNAs potentially involved in male sterility of Brassica
      campestris ssp. chinensis using microRNA array and quantitative RT-PCR assays.
AB  - microRNAs (miRNAs) are a class of newly identified, noncoding, small RNA
      molecules that negatively regulate gene expression. Many miRNAs are reportedly
      involved in plant growth, development and stress response processes. However,
      their roles in the sexual reproduction mechanisms in flowering plants remain
      unknown. Pollen development is an important process in the life cycle of a
      flowering plant, and it is closely related to the yield and quality of crop
      seeds. This study aimed to identify miRNAs involved in pollen development. A
      microarray assay was conducted using the known complementary sequences of plant
      miRNAs as probes on inflorescences of a sterile male line (Bcajh97-01A) and a
      fertile male line (Bcajh97-01B) of the Brassica campestris ssp. chinensis cv.
      'Aijiaohuang' genic male sterility sister line system (Bcajh97-01A/B). The
      results showed that 44 miRNAs were differently expressed in the two lines. Of
      these, 15 had over 1.5-fold changes in their transcript levels, with 9
      upregulated and 6 downregulated miRNAs in inflorescences of 'Bcajh97-01A' sterile
      line plants. We then focused on 3 of these 15 miRNAs (miR158, miR168 and miR172).
      Through computational methods, 13 family members were predicted for these 3
      miRNAs and 22 genes were predicted to be their candidate target genes. By using
      5' modified RACE, 2 target genes of miR168 and 5 target genes of miR172 were
      identified. Then, qRT-PCR was applied to verify the existence and expression
      patterns of the 3 miRNAs in the flower buds at five developmental stages. The
      results were generally consistent with those of the microarray. Thus, this study
      may give a valuable clue for further exploring the miRNA group that may function
      during pollen development. 

PMID- 23864335
TI  - Effects of caffeine on cortical epileptic afterdischarges in adult rats are
      modulated by postnatal treatment.
AB  - We have previously shown that the effect of acute caffeine injection on cortical
      epileptic afterdischarges (ADs) in immature rats can be modulated by the
      postnatal period of repeated caffeine treatment and age of testing during
      development. To know if these changes persist into adulthood, in the present
      study adult rats, previously exposed to caffeine from postnatal day 7-11 (10 and
      20 mg/kg), and injected with caffeine (10 and 20 mg/kg), respectively, at P67
      were compared with groups of naive rats on cortical epileptic ADs. Low-frequency
      stimulation of sensorimotor cortical area was applied repeatedly with increasing
      intensity of stimulation current. The acute caffeine injection decreased the
      thresholds for both the spike-and-wave ADs and accompanying clonic seizures in
      naive adult rats. In contrast, the acute caffeine administration applied to rats
      with postnatal caffeine treatment did not change the thresholds for ADs and
      clonic seizures. In addition, a shorter duration of ADs was registered at some
      stimulation intensities in rats with early postnatal caffeine administration.
      Present results demonstrated failure of proconvulsant effects of caffeine after
      repeated caffeine administration during the early postnatal period persisting up
      to adulthood.

PMID- 23864336
TI  - Factor XII activation markers do not reflect FXII dependence of thrombin
      generation induced by polyvinylchloride.
AB  - The role of factor XII (FXII) as the main trigger of the coagulation cascade
      during haemodialysis has been recently challenged. Polyvinylchloride (PVC) is the
      standard polymer for haemodialysis circuit tubings, but its interaction with FXII
      has not been extensively characterized. In a modified Chandler tubing loop model
      using heparinized fresh human whole blood we selectively inhibited coagulation
      factors VII, X or XII with monospecific antibodies. Contact of whole blood with
      PVC induced a strong thrombin generation [thrombin-antithrombin complexes (TAT)
      64 +/- 24 MUg/l, before <1 MUg/l]. Despite this, levels of FXII coagulation
      activity, free FXIIa or FXIIa-C1 inhibitor complexes remained unchanged. The anti
      FXII antibody abolished thrombin generation (TAT 8 +/- 5 MUg/l, P < 0.05) and
      made the free FXIIa undetectable. Inhibition of FVII did not affect coagulation
      activation (TAT 68 +/- 26 MUg/l). Our data provide definitive evidence that PVC
      triggers the coagulation system via FXII. However, all FXII activation markers in
      plasma failed to detect contact activation.

PMID- 23864337
TI  - Head impact exposure in youth football: high school ages 14 to 18 years and
      cumulative impact analysis.
AB  - Sports-related concussion is the most common athletic head injury with football
      having the highest rate among high school athletes. Traditionally, research on
      the biomechanics of football-related head impact has been focused at the
      collegiate level. Less research has been performed at the high school level,
      despite the incidence of concussion among high school football players. The
      objective of this study is to twofold: to quantify the head impact exposure in
      high school football, and to develop a cumulative impact analysis method. Head
      impact exposure was measured by instrumenting the helmets of 40 high school
      football players with helmet mounted accelerometer arrays to measure linear and
      rotational acceleration. A total of 16,502 head impacts were collected over the
      course of the season. Biomechanical data were analyzed by team and by player. The
      median impact for each player ranged from 15.2 to 27.0 g with an average value of
      21.7 (+/-2.4) g. The 95th percentile impact for each player ranged from 38.8 to
      72.9 g with an average value of 56.4 (+/-10.5) g. Next, an impact exposure metric
      utilizing concussion injury risk curves was created to quantify cumulative
      exposure for each participating player over the course of the season. Impacts
      were weighted according to the associated risk due to linear acceleration and
      rotational acceleration alone, as well as the combined probability (CP) of injury
      associated with both. These risks were summed over the course of a season to
      generate risk weighted cumulative exposure. The impact frequency was found to be
      greater during games compared to practices with an average number of impacts per
      session of 15.5 and 9.4, respectively. However, the median cumulative risk
      weighted exposure based on combined probability was found to be greater for
      practices vs. games. These data will provide a metric that may be used to better
      understand the cumulative effects of repetitive head impacts, injury mechanisms,
      and head impact exposure of athletes in football.

PMID- 23864338
TI  - A robust 3D finite element simulation of human proximal femur progressive
      fracture under stance load with experimental validation.
AB  - Clinical implementation of quantitative computed tomography-based finite element
      analysis (QCT/FEA) of proximal femur (hip) fractures requires (i) to develop a
      bone material behavior able to describe the progressive fracturing process until
      complete failure of the hip. And (ii) to validate the model with realistic test
      data that represent typical hip fractures. The objective of the current study was
      to develop and experimentally validate an accurate 3D finite element (FE) model
      coupled to a quasi-brittle damage law to simulate human proximal femur fracture
      considering the initiation and progressive propagation of multiple cracks phases
      under quasi-static load. The model is based on continuum damage mechanics that
      can predict hip fracture in more adequate physical terms than criteria-based
      fracture models. In order to validate the model, ten human proximal femurs were
      tested until complete fracture under one-legged stance quasi-static load. QCT/FE
      models were generated and FE simulations were performed on these femurs with the
      same applied loads and boundary conditions than in the stance experiments. The
      proposed FE model leads to excellent agreement (R(2) = 0.9432) between predicted
      and measured results concerning the shape of the force-displacement curve
      (yielding and fracturing) and the profile of the fractured edge. The motivation
      of this work was to propose a FE model for possible clinical use with a good
      compromise between complexity and capability of the simulation.

PMID- 23864339
TI  - Does des-acyl ghrelin improve glycemic control in obese diabetic subjects by
      decreasing acylated ghrelin levels?
AB  - OBJECTIVE: The objective of this study was to assess the effects of a continuous
      overnight infusion of des-acyl ghrelin (DAG) on acylated ghrelin (AG) levels and
      glucose and insulin responses to a standard breakfast meal (SBM) in eight
      overweight patients with type 2 diabetes. Furthermore, in the same patients and
      two additional subjects, the effects of DAG infusion on AG concentrations and
      insulin sensitivity during a hyperinsulinemic-euglycemic clamp (HEC) were
      assessed. RESEARCH DESIGN AND METHODS: A double-blind, placebo-controlled cross
      over study design was implemented, using overnight continuous infusions of 3 and
      10  MUg DAG/kg per h and placebo to study the effects on a SBM. During a HEC, we
      studied the insulin sensitivity. RESULTS: We observed that, compared with
      placebo, overnight DAG administration significantly decreased postprandial
      glucose levels, both during continuous glucose monitoring and at peak serum
      glucose levels. The degree of improvement in glycemia was correlated with
      baseline plasma AG concentrations. Concurrently, DAG infusion significantly
      decreased fasting and postprandial AG levels. During the HEC, 2.5  h of DAG
      infusion markedly decreased AG levels, and the M-index, a measure of insulin
      sensitivity, was significantly improved in the six subjects in whom we were able
      to attain steady-state euglycemia. DAG administration was not accompanied by many
      side effects when compared with placebo. CONCLUSIONS: DAG administration improves
      glycemic control in obese subjects with type 2 diabetes through the suppression
      of AG levels. DAG is a good candidate for the development of compounds in the
      treatment of metabolic disorders or other conditions with a disturbed AG:DAG
      ratio, such as type 2 diabetes mellitus or Prader-Willi syndrome.

PMID- 23864340
TI  - Preserved GLP-1 and exaggerated GIP secretion in type 2 diabetes and
      relationships with triglycerides and ALT.
AB  - OBJECTIVE: To i) compare incretin responses to oral glucose and mixed meal of
      diabetic patients with the normoglycaemic population and ii) to investigate
      whether incretin responses are associated with hypertriglyceridaemia and alanine
      aminotransferase (ALT) as liver fat marker. DESIGN: A population-based study.
      METHODS: A total of 163 persons with normal glucose metabolism (NGM), 20 with
      intermediate hyperglycaemia and 20 with type 2 diabetes aged 40-65 years
      participated. Participants received a mixed meal and oral glucose load on
      separate occasions. Glucagon-like peptide 1 (GLP-1), glucose-dependent
      insulinotropic polypeptide (GIP) and glucagon profiles were analysed as total
      area under the curve (tAUC) and incremental area under the curve. RESULTS: In
      diabetic patients compared with persons with NGM, we found increased GLP-1
      secretion (tAUC per hour) following oral glucose (23.2 pmol/l (95% CI 17.7-28.7)
      vs 18.0 (95% CI 16.9-19.1), P<0.05) but not after the mixed meal. GIP secretion
      among diabetic patients was increased on both occasions (82.9 pmol/l (55.9-109.8)
      vs 47.1 (43.8-50.4) for oral glucose and 130.6 (92.5-168.7) vs 83.2 (77.5-88.9)
      for mixed meal, both P<0.05). After oral glucose, GLP-1 (tAUC per hour) was
      inversely related to fasting triglycerides. GIP (tAUC per hour) was positively
      related to fasting and postprandial triglycerides. Higher fasting GIP levels were
      related to higher fasting and postprandial triglyceride levels and ALT.
      CONCLUSION: This study confirms that in type 2 diabetes, GLP-1 secretion is
      generally preserved and that GIP secretion is exaggerated. The mechanism
      underlying the divergent associations of GLP-1 and GIP metabolism with fat
      metabolism and liver fat accumulation warrants further study.

PMID- 23864341
TI  - Delayed diagnosis of Sheehan's syndrome in a developed country: a retrospective
      cohort study.
AB  - BACKGROUND: Little is known about Sheehan's syndrome (SS), even though it is
      believed that its incidence is low. The aims of this study were to determine the
      clinical features and diagnostic delay of SS and to ascertain whether early signs
      could have allowed earlier diagnosis. SUBJECTS AND METHODS: All patients with SS
      diagnosed in reference units in the southeast of France between 1980 and 2011
      were recruited for this study. Data on obstetrical history, clinical symptoms
      suggestive of hypopituitarism, early signs, hormone analysis, and magnetic
      resonance imaging were collected. RESULTS: Of the 40 women found to have SS, 39
      were studied. Mean delay in the diagnosis of SS was 9 +/- 9.7 years. We found
      that four of the 35 assessable patients were diagnosed with agalactia, 16 of the
      29 assessable ones with amenorrhea, 19 of the 39 with hypothyroidism, eight with
      acute adrenal insufficiency, and 15 with asthenia. Among the patients for whom
      there was a diagnostic delay of more than 1 year (n=28), seven had headaches
      during the postpartum period, all assessable patients had agalactia, six of the
      22 assessable ones had amenorrhea, seven of 28 had hypothyroidism, and 12 of 28
      had asthenia. CONCLUSION: Most signs of SS are aspecific and classical signs such
      as agalactia and amenorrhea are often difficult to detect, which can explain the
      long diagnostic delay. We suggest that all women failing to lactate after
      postpartum hemorrhage (PPH) should be evaluated by measuring prolactin levels and
      women with signs such as amenorrhea and asthenia, even several years after PPH,
      should undergo a blood test including assessment of thyroxine, TSH, 0800  h ACTH
      cortisol, and IGF1 levels.

PMID- 23864342
TI  - Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute
      myeloid leukemia.
AB  - A genome-wide serum miRNA expression analysis previously showed the upregulation
      of microRNA-375 (miR-375) in acute myeloid leukemia (AML) patients compared with
      healthy controls. The aim of this study was to investigate the expression
      patterns and the prognostic relevance of miR-375 in pediatric AML. Expression
      levels of miR-375 in bone marrow mononuclear cells were detected by real-time
      quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML.
      Expression levels of miR-375 in the bone marrow of pediatric AML patients were
      significantly higher than those in normal controls (P < 0.001). Then, miR-375
      upregulation occurred more frequently in French-American-British classification
      subtype M7 than in other subtypes (P < 0.001). Regarding to cytogenetic risk, the
      expression levels of miR-375 in pediatric AML patients with unfavorable
      karyotypes were dramatically higher than those in intermediate and favorable
      groups (P = 0.002). Moreover, high miR-375 expression was significantly
      associated with shorter relapse-free survival (P < 0.001) and overall survival (P
      < 0.001) in pediatric AML patients. Multivariate analysis further identified miR
      375 expression and cytogenetics risk as independent prognostic factors for both
      relapse-free survival and overall survival. In particular, the prognostic
      relevance of miR-375 expression was more obvious in the subgroup of patients with
      intermediate-risk cytogenetics. Our findings suggest for the first time that the
      upregulation of miR-375 may be one of the molecular mechanisms involved in the
      development and progression of pediatric AML. Since its correlation with poor
      relapse-free survival and overall survival, miR-375 may be a novel biomarker to
      improve the management of pediatric AML patients.

PMID- 23864343
TI  - Optimized expression of (S)-carbonyl reductase in Pichia pastoris for efficient
      production of (S)-1-phenyl-1, 2-ethanediol.
AB  - The recombinant (S)-carbonyl reductase (SCR) in Escherichia coli catalyzed the
      reduction of 2-hydroxyacetophenone to (S)-1-phenyl-1,2-ethanediol (PED) with low
      efficiency. In this work, its 6* histidine fusion gene his6 -scr was cloned in
      Pichia pastoris under the control of the AOX1 methanol inducible promoter. The
      heterologous protein SCR was expressed through a Mut(s) phenotype. Under the
      optimal conditions: pH 7.0, initial OD600 2.5, methanol daily addition
      concentration 1.0% and induction duration 4-5 days, the recombinant protein SCR
      was produced at the highest level. The enzyme activity in the cell-free exacts of
      P. pastoris was 0.38, which was over twofold than that of the recombinant E. coli
      SCR. The enzyme was purified to homogeneity with a specific activity of 3.41 U
      mg(-1) , and it catalyzed the biotransformation of (S)-PED with a high optical
      purity of 96.9% in a high yield of 89.7% at optimum pH of 7.0. The developed
      effective system of P. pastoris-SCR will facilitate the preparation of pure
      chiral alcohol in industry. 

PMID- 23864345
TI  - Assessing adolescent asthma symptoms and adherence using mobile phones.
AB  - BACKGROUND: Self-report is the most common method of measuring medication
      adherence but is influenced by recall error and response bias, and it typically
      does not provide insight into the causes of poor adherence. Ecological momentary
      assessment (EMA) of health behaviors using mobile phones offers a promising
      alternative to assessing adherence and collecting related data that can be
      clinically useful for adherence problem solving. OBJECTIVE: To determine the
      feasibility of using EMA via mobile phones to assess adolescent asthma medication
      adherence and identify contextual characteristics of adherence decision making.
      METHODS: We utilized a descriptive and correlational study design to explore a
      mobile method of symptom and adherence assessment using an interactive voice
      response system. Adolescents aged 12-18 years with a diagnosis of asthma and
      prescribed inhalers were recruited from an academic medical center. A survey
      including barriers to mobile phone use, the Illness Management Survey, and the
      Pediatric Asthma Quality of Life Questionnaire were administered at baseline.
      Quantitative and qualitative assessment of asthma symptoms and adherence were
      conducted with daily calls to mobile phones for 1 month. The Asthma Control Test
      (ACT) was administered at 2 study time points: baseline and 1 month after
      baseline. RESULTS: The sample consisted of 53 adolescents who were primarily
      African American (34/53, 64%) and female (31/53, 58%) with incomes US$40K/year or
      lower (29/53, 55%). The majority of adolescents (37/53, 70%) reported that they
      carried their phones with them everywhere, but only 47% (25/53) were able to use
      their mobile phone at school. Adolescents responded to an average of 20.1 (SD
      8.1) of the 30 daily calls received (67%). Response frequency declined during the
      last week of the month (b=-0.29, P<.001) and was related to EMA-reported levels
      of rescue inhaler adherence (r= 0.33, P=.035). Using EMA, adolescents reported an
      average of 0.63 (SD 1.2) asthma symptoms per day and used a rescue inhaler an
      average of 70% of the time (SD 35%) when they experienced symptoms. About half
      (26/49, 53%) of the instances of nonadherence took place in the presence of
      friends. The EMA-measured adherence to rescue inhaler use correlated
      appropriately with asthma control as measured by the ACT (r=-0.33, P=.034).
      CONCLUSIONS: Mobile phones provided a feasible method to assess asthma symptoms
      and adherence in adolescents. The EMA method was consistent with the ACT, a
      widely established measure of asthma control, and results provided valuable
      insights regarding the context of adherence decision making that could be used
      clinically for problem solving or as feedback to adolescents in a mobile or Web
      based support system.

PMID- 23864346
TI  - Kidney volume and function in autosomal dominant polycystic kidney disease.
AB  - BACKGROUND: The significance of total kidney volume (TKV) as a biomarker of
      kidney function in autosomal dominant polycystic kidney disease (ADPKD) is
      controversial and has been reappraised. METHODS: Between 2007 and 2012, 64
      patients were followed with a mean 39.7-month observation period. TKV
      measurements by magnetic resonance imaging and estimation of renal function with
      estimated glomerular filtration rate (eGFR) using the Modification of Diet in
      Renal Disease equation and 24-h urine creatinine clearance were repeated
      annually. RESULTS: TKV and its adjusted parameters (height-adjusted, body surface
      area-adjusted and log-converted TKV [log-TKV]) correlated with eGFR
      significantly. Among them, the correlation coefficient of log-TKV was most
      significant (r = -0.6688, p < 0.001). The eGFR slope correlated negatively with
      TKV slope (p < 0.05). TKV increased faster and became larger as chronic kidney
      disease (CKD) stage advanced. As age advanced, eGFR declined significantly (p <
      0.001), but the eGFR slope remained constant. There was no significant
      correlation between TKV and age, but the log-TKV slope became smaller as age
      advanced. If baseline TKV was large, the eGFR slope was steeper (p < 0.05), which
      suggests that eGFR declines faster in patients with larger kidney volume.
      CONCLUSIONS: TKV is confirmed as a clinically meaningful surrogate marker in
      ADPKD. Log-TKV correlates with eGFR most significantly. Higher rates of kidney
      enlargement and larger kidney volume are associated with a more rapid decrease in
      kidney function. Kidney function decreased faster as CKD stage advanced, but its
      declining slope did not change significantly by age, at least after ~30 years of
      age.

PMID- 23864344
TI  - Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease.
AB  - Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large
      proportion of elderly dementia cases. The current definition of HS-Aging rests on
      pathologic criteria: neuronal loss and gliosis in the hippocampal formation that
      is out of proportion to AD-type pathology. HS-Aging is also strongly associated
      with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the
      oldest-old: autopsy series indicate that 5-30 % of nonagenarians have HS-Aging
      pathology. Among prior studies, differences in study design have contributed to
      the study-to-study variability in reported disease prevalence. The presence of HS
      Aging pathology correlates with significant cognitive impairment which is often
      misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by
      other diseases linked to hippocampal atrophy including frontotemporal lobar
      degeneration and cerebrovascular pathologies. Recent advances characterizing the
      neurocognitive profile of HS-Aging patients have begun to provide clues that may
      help identify living individuals with HS-Aging pathology. Structural brain
      imaging studies of research subjects followed to autopsy reveal hippocampal
      atrophy that is substantially greater in people with eventual HS-Aging pathology,
      compared to those with AD pathology alone. Data are presented from individuals
      who were followed with neurocognitive and neuroradiologic measurements, followed
      by neuropathologic evaluation at the University of Kentucky. Finally, we discuss
      factors that are hypothesized to cause or modify the disease. We conclude that
      the published literature on HS-Aging provides strong evidence of an important and
      under-appreciated brain disease of aging. Unfortunately, there is no therapy or
      preventive strategy currently available.

PMID- 23864349
TI  - Hyponatremia associated with primary central nervous system lymphoma.

PMID- 23864347
TI  - Decreased urinary calbindin 1 levels in proteinuric rats and humans with distal
      nephron segment injuries.
AB  - BACKGROUND: Several proteins have been proposed as new urinary biomarkers of
      kidney injuries, but they are not always capable of identifying the kidney
      nephron segment that has been injured. Since calbindin 1 protein is exclusively
      localized in the kidney distal nephron segment, it is presumed that its
      expression is altered during distal nephron segment injuries, resulting in
      changes in its urinary excretion. METHODS: Calbindin 1 expression in normal rat
      kidneys was compared with that in the kidneys of rats that had suffered distal
      nephron segment injuries (unilateral ureteral obstruction [UUO] or anti
      glomerular basement membrane glomerulonephritis [anti-GBM GN]) using
      immunohistochemical examinations and real-time polymerase chain reaction. The
      urinary calbindin 1 protein concentration of normal rats was also compared with
      that of anti-GBM GN rats and of cisplatin nephropathy rats using Western
      blotting. We also compared the kidney and urinary calbindin 1 protein
      concentrations of normal human subjects with those of proteinuric patients
      [immunoglobulin (Ig)A nephropathy; IgAN] with distal nephron segment injuries.
      RESULTS: Calbindin 1 mRNA expression in the renal cortices and calbindin 1
      protein expression in the kidney distal nephron segments were decreased in the
      UUO and anti-GBM GN rat kidneys. The urinary calbindin 1 protein levels of the
      anti-GBM GN rats were also markedly decreased, whereas those of the cisplatin
      nephropathy rats were slightly decreased. The human IgAN patients displayed
      decreased renal calbindin 1 protein expression in their dilated distal tubules,
      and some patients displayed decreased urinary calbindin 1 levels. CONCLUSION:
      Since it has been demonstrated that decreased urinary calbindin 1 levels are
      indicative of decreased calbindin 1 kidney expression due to distal nephron
      segment injuries, calbindin 1 might be a useful urinary biomarker for identifying
      distal nephron segment injuries.

PMID- 23864350
TI  - Final adult height in kidney recipients who underwent highly successful
      transplantation as children: a single-center experience.
AB  - BACKGROUND: Achieving a normal final adult height (FH) remains a challenge in the
      field of pediatric kidney transplantation (KTx). To examine the optimal approach
      to assuring normal FH following KTx, we retrospectively examined the post
      transplant growth and FH of pediatric KTx recipients. METHODS: Since the relevant
      factors affecting the FH of children following KTx are multifactorial and notably
      complex, KTx recipients with persistent good graft function and successful
      steroid minimization until FH attainment were selected for this study. RESULTS:
      Thirteen patients were enrolled in this study. The mean estimated glomerular
      filtration rate was 72.1 +/- 15.3 ml/min/1.73 m(2), and the mean corticosteroid
      dose was 0.05 +/- 0.05 mg/kg on alternate days at the time of FH attainment.
      Despite highly successful KTx, four (30.8 %) patients (one who underwent KTx
      before puberty and three during puberty) showed a decrease in the height standard
      deviation score (hSDS) from the time of KTx until FH attainment. Moreover, of
      these, two male patients had an FH with an SD <-2. CONCLUSION: FH remained
      suboptimal despite highly successful KTx. Not only highly successful KTx but also
      further treatment such as steroid avoidance, early steroid withdrawal or using
      rhGH might be necessary to assure a normal FH in some pubertal patients.

PMID- 23864351
TI  - The third wave in health sciences education.

PMID- 23864352
TI  - Projected climate impacts to South African maize and wheat production in 2055: a
      comparison of empirical and mechanistic modeling approaches.
AB  - Crop model-specific biases are a key uncertainty affecting our understanding of
      climate change impacts to agriculture. There is increasing research focus on
      intermodel variation, but comparisons between mechanistic (MMs) and empirical
      models (EMs) are rare despite both being used widely in this field. We combined
      MMs and EMs to project future (2055) changes in the potential distribution
      (suitability) and productivity of maize and spring wheat in South Africa under 18
      downscaled climate scenarios (9 models run under 2 emissions scenarios). EMs
      projected larger yield losses or smaller gains than MMs. The EMs' median
      projected maize and wheat yield changes were -3.6% and 6.2%, respectively,
      compared to 6.5% and 15.2% for the MM. The EM projected a 10% reduction in the
      potential maize growing area, where the MM projected a 9% gain. Both models
      showed increases in the potential spring wheat production region (EM = 48%, MM =
      20%), but these results were more equivocal because both models (particularly the
      EM) substantially overestimated the extent of current suitability. The
      substantial water-use efficiency gains simulated by the MMs under elevated CO2
      accounted for much of the EM-MM difference, but EMs may have more accurately
      represented crop temperature sensitivities. Our results align with earlier
      studies showing that EMs may show larger climate change losses than MMs. Crop
      forecasting efforts should expand to include EM-MM comparisons to provide a
      fuller picture of crop-climate response uncertainties.

PMID- 23864353
TI  - Minority stress and physical health among sexual minority individuals.
AB  - This study examined the effects of minority stress on the physical health of
      lesbians, gay men, and bisexuals (LGBs). Participants (N = 396) completed
      baseline and one year follow-up interviews. Exposure to stress and health
      outcomes were assessed with two methods: a subjective self-appraisal method and a
      method whereby two independent judges externally rated event narratives using
      standardized criteria. The odds of experiencing a physical health problem at
      follow-up were significantly higher among LGBs who experienced an externally
      rated prejudice event during the follow-up period compared to those who did not.
      This association persisted after adjusting for experiences of general stressful
      life events that were not related to prejudice. Self-appraised minority stress
      exposures were not associated with poorer physical health at 1-year follow-up.
      Prejudice-related stressful life events have a unique deleterious impact on
      health that persists above and beyond the effect of stressful life events
      unrelated to prejudice.

PMID- 23864354
TI  - Species-specific microRNA regulation influences phenotypic variability:
      perspectives on species-specific microRNA regulation.
AB  - Phenotypic divergence among animal species may be due in part to species-specific
      (SS) regulation of gene expression by small, non-coding regulatory RNAs termed
      "microRNAs". This phenomenon can be modulated by several variables. First,
      microRNA genes vary by their level of conservation, many of them being SS, or
      unique to a particular evolutionary lineage. Second, microRNA expression levels
      vary spatially and temporally in different species. Lastly, while microRNAs bind
      the 3'UTR of target genes in order to silence their expression, the binding sites
      themselves are often non-conserved. The variability of the miRNA-target paradigm
      between different species is thus multifactorial, and this paradigm has only just
      started to gain attention from researchers in various fields. Here we present and
      discuss recent findings regarding the characteristics and implications of SS
      microRNA regulation.

PMID- 23864355
TI  - Infantile haemangiomas and quality of life.
AB  - OBJECTIVE: To determine the quality of life (QOL) and self-esteem of children
      with infantile haemangiomas using objective measures. DESIGN: Twenty-one
      children, 5-8 years old, with a diagnosis of head or neck haemangioma measuring 2
      cm or more, were compared with 22 children with no history of haemangioma.
      SETTING: A tertiary medical centre in the north of Israel. INTERVENTIONS:
      Demographic and clinical details were collected, followed by two questionnaires
      Paediatric Quality of Life Inventory (PedsQL) and Harter pictorial scale of
      Perceived Competence and Social Acceptance for young children-answered by
      children and parents of the two groups. MAIN OUTCOME MEASURES: QOL and self
      esteem of the children in the two groups. RESULTS: There were no significant
      differences in QOL indices or self-perception scores between children with and
      without haemangioma (86.6+/-10.3 vs 80.1+/-15.07, p=0.23 and 3.62+/-0.2 vs 3.72+/
      0.21, p=0.17, respectively). Interestingly, parents of children with haemangioma
      reported higher QOL of their children than parents of children without
      haemangioma (86.4+/-9.6 vs 77.1+/-14.9, p<0.03). Likewise, a positive correlation
      between parents' scored PedsQL and children's scored PedsQL was found (0.56,
      p=0.008). CONCLUSIONS: The findings raise a question about aggressive as opposed
      to more conservative treatment, especially in the era of propranolol.

PMID- 23864356
TI  - Rapid home-based weaning of small children with feeding tube dependency: positive
      effects on feeding behaviour without deceleration of growth.
AB  - BACKGROUND: Oral aversion and feeding disorders occur frequently after long-term
      feeding via a tube. A rapid home-based tube-weaning programme that provides
      feeding disorder treatment under medical supervision to overcome oral aversion
      has been developed. AIMS: To describe the results of the 4-10-day rapid home
      based feeding tube-weaning programme and to determine the prevalence of food
      aversion and the overall longitudinal effects on feeding behaviour and growth
      after treatment. SUBJECTS AND METHODS: The parents of children who participated
      in the programme between 2005 and 2007 were followed up via questionnaire in
      2008. The questionnaire included inquiries about the characteristics of tube
      feeding, feeding behaviour and growth parameters. RESULTS: The study group
      comprised of 18 boys and 21 girls who, at entry, had a median age of 16 months
      (range, 5-57) and a median duration of tube feeding of 15 months (range, 3-56).
      The children were followed up for a median of 2 years after treatment (range, 1-3
      years). The weaning programme established oral feeding in 89.7% of the children.
      In all cases where oral feeding was achieved, the feeding behaviour improved
      after treatment. The growth velocity of all children, as indicated by weight,
      length and body mass index (BMI), remained constant from the initial evaluation
      (BMI z-score M=-1.1 +/- 1.7) to follow-up (BMI z-score M=-1.2 +/- 1.1).
      CONCLUSIONS: This rapid weaning programme for children with feeding tube
      dependency (FTD) improved the feeding behaviour and was associated with constant
      growth velocity.

PMID- 23864357
TI  - Is paracetamol safe and effective for ductus arteriosus closure?

PMID- 23864358
TI  - Papineau debridement, Ilizarov bone transport, and negative-pressure wound
      closure for septic bone defects of the tibia.
AB  - PURPOSE: Ilizarov pioneered bone transport using a circular external fixator.
      Papineau described a staged technique for the treatment for infected
      pseudarthrosis of the long bones. This article presents a single-stage Papineau
      technique and Ilizarov bone transport, and postoperative negative-pressure wound
      dressing changes for septic bone defects of the tibia. MATERIALS AND METHODS: We
      studied the files of seven patients (mean age, 32 years) with septic bone defects
      of the tibia treated with a Papineau technique and Ilizarov bone transport in a
      single stage, followed by postoperative negative-pressure wound dressing changes.
      All patients had septic pseudarthrosis and skin necrosis of the tibia. The
      technique included a single-stage extensive surgical debridement of necrotic
      bone, open bone grafting with cancellous bone autograft and bone transport, and
      postoperative negative-pressure wound dressing changes for wound closure. The
      mean time from the initial injury was 6 months (range, 4-8 months). The mean
      follow-up was 14 months (range, 10-17 months). RESULTS: All patients experienced
      successful wound healing at a mean of 29 days. Six patients experienced
      successful bone regeneration and union at the docking side at a mean of 6 months.
      One patient experienced delayed union at the docking site, which was treated with
      autologous cancellous bone grafting. Two patients experienced pin track
      infection, which was successfully treated with antibiotics and pin site dressing
      changes. All patients were able to return to their work and previous levels of
      activity, except one patient who had a stiff ankle joint and had to change his
      job. No patient experienced recurrence of infection, or fracture of the
      regenerated or transported bone segment until the period of this study.
      CONCLUSION: The combined Papineau and Ilizarov bone transport technique with
      negative-pressure wound closure provides for successful eradication of the
      infection, reconstruction of the bone defect, and soft-tissue closure. A single
      stage surgical treatment is feasible, without any complications.

PMID- 23864359
TI  - Target of tae-miR408, a chemocyanin-like protein gene (TaCLP1), plays positive
      roles in wheat response to high-salinity, heavy cupric stress and stripe rust.
AB  - microRNAs (miRNAs) are novel and significant regulators of gene expression at the
      post-transcriptional level, and they are essential for normal growth and
      development and adaptation to stress conditions. As miRNAs are a kind of RNAs
      that do not code proteins, they play roles by repressing gene translation or
      degrading the corresponding target mRNAs. Plantacyanin-like (basic blue) proteins
      have been predicted and verified as the target gene of miR408 in wheat and
      Arabidopsis, respectively. Besides some biochemical characteristics, their
      detailed biological function remains unknown. In this study, the target gene of a
      wheat miRNA (tae-miR408), designated TaCLP1, was identified using degradome
      sequencing and co-transformation technology in tobacco leaves. We isolated the
      full-length cDNA clone, and defined its product as a chemocyanin-like protein, a
      kind of plantacyanin. Transcript accumulation of TaCLP1 and tae-miR408 showed
      contrasting divergent expression patterns in wheat response to Puccinia
      striiformis f. sp. tritici (Pst) and high copper ion stress. Overexpression of
      TaCLP1 in yeast (Schizosaccharomyces pombe) significantly increased cell growth
      under high salinity and Cu2+ stresses. Silencing of individual cDNA clones in
      wheat challenged with Pst indicated that TaCLP1 positively regulates resistance
      to stripe rust. The results indicate that the target of tae-miR408, TaCLP1, play
      an important role in regulating resistance of host plants to abiotic stresses and
      stripe rust, and such interactions can be a valuable resource for investigating
      stress tolerance in wheat.

PMID- 23864361
TI  - Inside ventilatory regulation in pulmonary hypertension: several hidden data are
      still undiscovered.
AB  - During exercise, ventilation for a given work rate is increased in pulmonary
      hypertension. In the present editorial a new look at the ventilatory behaviour,
      which may change the common approach to VE/VCO2 relationship analysis, is
      presented. 

PMID- 23864360
TI  - Non-telomeric epigenetic and genetic changes are associated with the inheritance
      of shorter telomeres in mice.
AB  - Studies using human and mouse cells have revealed some changes to non-telomeric
      chromatin and gene expression in response to abnormally short telomeres. To
      investigate this further, we studied the effect of inheriting shorter telomeres
      on transcription and genetic stability at non-telomeric sites in the mouse. Using
      multiple generations of Terc knockout mice, we show that inheriting shorter
      telomeres from one parent increases the likelihood of transcriptional silencing
      at a non-telomeric green fluorescent protein (GFP) transgene inherited from the
      other parent. In these cases, silencing must occur at or after zygote formation.
      In grand-offspring from a G3 Terc (-/-) parent, transgene expression was further
      reduced and associated with increased DNA methylation and, surprisingly, reduced
      copy number at the transgene array. In these cases, the transgene had been passed
      through the germline of a Terc-compromised parent, providing an opportunity for
      meiotic events. Furthermore, genome-wide microarray analysis of copy number
      variations revealed greater genetic instability in G3 Terc (-/-) mice than
      detected in wild-type mice of the same genetic background. Our results have
      implications for the molecular mechanisms underlying premature-ageing syndromes,
      such as dyskeratosis congenita. In autosomal-dominant dyskeratosis congenita,
      progressive telomere shortening is seen as it passes down the generations, and
      this is associated with anticipation, i.e. the disease becomes more severe
      earlier. The underlying mechanism is not known, but has been considered to be
      simply associated with decreases in telomere length. Epigenetic and/or genetic
      changes at non-telomeric regions could, in theory, be involved. 

PMID- 23864362
TI  - The Korean Heart Study: rationale, objectives, protocol, and preliminary results
      for a new prospective cohort study of 430,920 men and women.
AB  - BACKGROUND: To describe the rationale, objectives, protocol, and preliminary
      results for a new prospective cohort study of cardiovascular disease (CVD) risk
      factors in South Korea. METHODS: Study members were recruited from participants
      in routine health assessments at health promotion centres across South Korea.
      Established and emerging CVD risk factors were measured. Eighteen centres holding
      electronic health records agreed to linkage of participants' records to future
      health insurance claims for monitoring of disease events. The recruitment of
      430,920 participants (266,782 men, 164,138 women), aged 30-74 years, provides
      broad geographical reach across South Korea. RESULTS: Risk factor prevalence was
      more favourable in women than men, and, in general, in the younger rather than
      older study members. There was also close similarity between the characteristics
      of the present sample and the Korean National Health and Nutrition Examination
      Survey. The expected associations between risk factors and both CVD and death
      were also apparent. CONCLUSIONS: Data from the present sample, based on data
      linkage, show close agreement with South Korea-wide surveys (for risk factor
      prevalence) and the extant literature (for risk factor associations). These
      findings gives confidence in future results anticipated from this cohort study of
      east Asians - a group that has been traditionally under-researched.

PMID- 23864363
TI  - Effects of inspiratory muscle training in patients with heart failure with
      preserved ejection fraction.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is remarkably
      common in elderly people with highly prevalent comorbid conditions. Despite its
      increasing in prevalence, there is no evidence-based effective therapy for HFpEF.
      We sought to evaluate whether inspiratory muscle training (IMT) improves exercise
      capacity, as well as left ventricular diastolic function, biomarker profile and
      quality of life (QoL) in patients with advanced HFpEF and nonreduced maximal
      inspiratory pressure (MIP). DESIGN AND METHODS: A total of 26 patients with HFpEF
      (median (interquartile range) age, peak exercise oxygen uptake (peak VO2) and
      left ventricular ejection fraction of 73 years (66-76), 10 ml/min/kg (7.6-10.5)
      and 72% (65-77), respectively) were randomized to receive a 12-week programme of
      IMT plus standard care vs. standard care alone. The primary endpoint of the study
      was evaluated by positive changes in cardiopulmonary exercise parameters and
      distance walked in 6 minutes (6MWT). Secondary endpoints were changes in QoL,
      echocardiogram parameters of diastolic function, and prognostic biomarkers.
      RESULTS: The IMT group improved significantly their MIP (p < 0.001), peak VO2 (p
      < 0.001), exercise oxygen uptake at anaerobic threshold (p = 0.001), ventilatory
      efficiency (p = 0.007), metabolic equivalents (p < 0,001), 6MWT (p < 0.001), and
      QoL (p = 0.037) as compared to the control group. No changes on diastolic
      function parameters or biomarkers levels were observed between both groups.
      CONCLUSIONS: In HFpEF patients with low aerobic capacity and non-reduced MIP, IMT
      was associated with marked improvement in exercise capacity and QoL.

PMID- 23864364
TI  - Associations between health care seeking and socioeconomic and demographic
      determinants among people reporting alarm symptoms of cancer: a population-based
      cross-sectional study.
AB  - BACKGROUND: Late diagnosis of cancer may partly be explained by the fact that
      some patients do not seek health care promptly when experiencing an alarm
      symptom. Socioeconomic and demographic differences exist concerning knowledge and
      awareness of cancer alarm symptoms in the general population and socioeconomic
      differences are found in cancer incidence and survival. We therefore hypothesise
      that socioeconomic and demographic differences in health care-seeking behaviour
      are present among people with alarm symptoms. OBJECTIVES: To analyse associations
      between health care seeking and socioeconomic and demographic factors among
      people reporting cancer alarm symptoms. METHODS: A questionnaire survey
      comprising 20000 people aged >20 from the Danish population. The questionnaire
      concerned alarm symptoms of common cancers and subsequent health care seeking.
      Data on socioeconomic factors were obtained from Statistics Denmark. MAIN
      OUTCOMES: health care seeking and patient interval. RESULTS: A total of 26.1% of
      all subjects reported that they did not seek health care when having experienced
      an alarm symptom. Women-subjects aged >40, subjects living with a partner and
      subjects having a cancer diagnosis-were more likely to seek health care, whereas
      medium educational level was negatively associated with health care seeking.
      Further, women were more likely to seek health care within 1 month, whereas
      subjects out of the workforce were less likely to do so. CONCLUSIONS:
      Approximately three out of four subjects sought health care when having
      experienced an alarm symptom but 50% waited for at least 1 month. Some
      demographic factors were found to be associated with health care-seeking
      behaviour and the patient interval, whereas no consistent associations were found
      with regard to socioeconomics.

PMID- 23864365
TI  - Public funding of pharmaceuticals in The Netherlands: investigating the effect of
      evidence, process and context on CVZ decision-making.
AB  - The College Voor Zorgverzekeringen (CVZ) provides guidance to the Dutch
      healthcare system on funding and use of new pharmaceutical technologies. This
      study examined the impact of evidence, process and context factors on CVZ
      decisions in 2004-2009. A data set of CVZ decisions pertaining to pharmaceutical
      technologies was created, including 29 variables extracted from published
      information. A three-category outcome variable was used, defined as the decision
      to 'recommend', 'restrict' or 'not recommend' a technology. Technologies included
      in list 1A/1B or on the expensive drug list were considered recommended; those
      included in list 2 or for which patient co-payment is required were considered
      restricted; technologies not included on any reimbursement list were classified
      as 'not recommended'. Using multinomial logistic regression, the relative
      contribution of explanatory variables on CVZ decisions was assessed. In all, 244
      technology appraisals (256 technologies) were analysed, with 51%, of technologies
      recommended, 33% restricted and 16% not recommended by CVZ for funding. The
      multinomial model showed significant associations (p <= 0.10) between CVZ outcome
      and several variables, including: (1) use of an active comparator and
      demonstration of statistical superiority of the primary endpoint in clinical
      trials, (2) pharmaceutical budget impact associated with introduction of the
      technology, (3) therapeutic indication and (4) prevalence of the target
      population. Results confirm the value of a comprehensive and multivariate
      approach to understanding CVZ decision-making.

PMID- 23864366
TI  - Lead me not into temptation: drug price regulation and dispensing physicians in
      Switzerland.
AB  - While most countries separate drug prescription and dispensation to ensure
      independent drug choice, some allow this combination to increase pharmaceutical
      access in rural areas or to increase the utilization of pharmacist skills. A
      drawback of this approach is that dispensing physicians or prescribing
      pharmacists may be incentivized to increase their own profits through the
      prescription of cost-inefficient drug packages, leading to an increase in
      pharmaceutical spending. Switzerland constitutes an interesting example of where
      dispensing and non-dispensing physicians coexist, permitting a comparison of
      their prescribing behavior. The present study shows that drug margin optimization
      is possible under the current drug price regulation scheme in Switzerland. Using
      drug claims data, empirical findings indicate a 5-10% higher margin per dose for
      dispensing physicians compared to pharmacists. Cost per dose is 3-5% higher when
      dispensed by physicians instead of pharmacists.

PMID- 23864367
TI  - Biomaterials for spinal cord repair.
AB  - Spinal cord injury (SCI) results in permanent loss of function leading to often
      devastating personal, economic and social problems. A contributing factor to the
      permanence of SCI is that damaged axons do not regenerate, which prevents the re
      establishment of axonal circuits involved in function. Many groups are working to
      develop treatments that address the lack of axon regeneration after SCI. The
      emergence of biomaterials for regeneration and increased collaboration between
      engineers, basic and translational scientists, and clinicians hold promise for
      the development of effective therapies for SCI. A plethora of biomaterials is
      available and has been tested in various models of SCI. Considering the clinical
      relevance of contusion injuries, we primarily focus on polymers that meet the
      specific criteria for addressing this type of injury. Biomaterials may provide
      structural support and/or serve as a delivery vehicle for factors to arrest
      growth inhibition and promote axonal growth. Designing materials to address the
      specific needs of the damaged central nervous system is crucial and possible with
      current technology. Here, we review the most prominent materials, their optimal
      characteristics, and their potential roles in repairing and regenerating damaged
      axons following SCi. 

PMID- 23864369
TI  - Different populations of subthalamic neurons encode cocaine vs. sucrose reward
      and predict future error.
AB  - The search for treatment of cocaine addiction raises the challenge to find a way
      to diminish motivation for the drug without decreasing it for natural rewards.
      Subthalamic nucleus (STN) inactivation decreases motivation for cocaine while
      increasing motivation for food, suggesting that STN can dissociate different
      rewards. Here, we investigated how rat STN neurons respond to cues predicting
      cocaine or sucrose and to reward delivery while rats are performing a
      discriminative stimuli task. We show that different neuronal populations of STN
      neurons encode cocaine and sucrose. In addition, we show that STN activity at the
      cue onset predicts future error. When changing the reward predicted unexpectedly,
      STN neurons show capacities of adaptation, suggesting a role in reward-prediction
      error. Furthermore, some STN neurons show a response to executive error (i.e.,
      "oops neurons") that is specific to the missed reward. These results position the
      STN as a nexus where natural rewards and drugs of abuse are coded differentially
      and can influence the performance. Therefore, STN can be viewed as a structure
      where action could be taken for the treatment of cocaine addiction. 

PMID- 23864368
TI  - Association of the Kv1 family of K+ channels and their functional blueprint in
      the properties of auditory neurons as revealed by genetic and functional
      analyses.
AB  - Developmental plasticity in spiral ganglion neurons (SGNs) ensues from profound
      alterations in the functional properties of the developing hair cell (HC). For
      example, prehearing HCs are spontaneously active. However, at the posthearing
      stage, HC membrane properties transition to graded receptor potentials. The
      dendrotoxin (DTX)-sensitive Kv1 channel subunits (Kv1.1, 1.2, and 1.6) shape the
      firing properties and membrane potential of SGNs, and the expression of the
      channel undergoes developmental changes. Because of the stochastic nature of Kv
      subunit heteromultimerization, it has been difficult to determine physiologically
      relevant subunit-specific interactions and their functions in the underlying
      mechanisms of Kv1 channel plasticity in SGNs. Using Kcna2 null mutant mice, we
      demonstrate a surprising paradox in changes in the membrane properties of SGNs.
      The resting membrane potential of Kcna2(-/-) SGNs was significantly
      hyperpolarized compared with that of age-matched wild-type (WT) SGNs. Analyses of
      outward currents in the mutant SGNs suggest an apparent approximately twofold
      increase in outward K(+) currents. We show that in vivo and in vitro
      heteromultimerization of Kv1.2 and Kv1.4 alpha-subunits underlies the striking
      and unexpected alterations in the properties of SGNs. The results suggest that
      heteromeric interactions of Kv1.2 and Kv1.4 dominate the defining features of Kv1
      channels in SGNs. 

PMID- 23864370
TI  - Homocysteine reduces NMDAR desensitization and differentially modulates peak
      amplitude of NMDAR currents, depending on GluN2 subunit composition.
AB  - N-methyl-d-aspartate receptors (NMDARs) have been linked to schizophrenia because
      agents that bind the receptor, like ketamine and phencyclidine, are capable of
      inducing schizophrenia-like symptoms. Here we show that the amino acid
      homocysteine (HCY), which is increased in the blood of schizophrenia patients,
      reduces desensitization of NMDARs in cultured mouse neurons, human embryonic
      kidney cells transfected with GluN1 + GluN2A, GluN2B, or GluN2D subunits, and
      hippocampal slices. HCY also alters the peak amplitude of NMDAR currents,
      depending on the GluN2 subunit the receptor contains; GluN1 + GluN2A-containing
      NMDARs show an increase in peak amplitude when exposed to HCY, while GluN1 +
      GluN2B-containing NMDARs show a decrease in peak amplitude. Both peak amplitude
      and desensitization effects of HCY can be occluded by saturating the NMDAR with
      glycine. Since glycine concentrations are not saturating in the brain, HCY could
      play an NMDAR-modulating role in the nervous system. We also show that HCY shares
      characteristics with glutamate and suggest that HCY affects both the agonist and
      co-agonist site of the NMDAR. 

PMID- 23864371
TI  - Developmental improvements in dynamic control of fingertip forces last throughout
      childhood and into adolescence.
AB  - While it is clear that the development of dexterous manipulation in children
      exhibits dramatic improvements over an extended period, it is difficult to
      separate musculoskeletal from neural contributors to these important functional
      gains. This is in part due to the inability of current methods to disambiguate
      improvements in hand strength from gains in finger dexterity (i.e., the dynamic
      control of fingertip force vectors at low magnitudes). We adapted our novel
      instrumentation to evaluate finger dexterity in 130 typically developing children
      between the ages of 4 and 16 yr. We find that finger dexterity continues to
      develop well into late adolescence and musculoskeletal growth and strength are
      poorly correlated with the improvements in dexterity. Importantly, because these
      behavioral results seem to mirror the known timelines of neuroanatomical
      development up to adolescence, we speculate that they reflect the functional
      benefits of such continual neural maturation. This novel perspective now enables
      the systematic study of the functional roles of specific neuroanatomical
      structures and their connectivity, maturity, and plasticity. Moreover, the
      temporal dynamics of the fingertip force vectors shows improvements in stability
      that provide a novel way to look at the maturation of finger control. From a
      clinical perspective, our results provide a practical means to chart functional
      development of dexterous manipulation in typically developing children and could
      be adapted for clinical use and for use in children with developmental disorders.

PMID- 23864372
TI  - Dynamic effects of TNF-alpha on synaptic transmission in mice over time following
      sciatic nerve chronic constriction injury.
AB  - Nerve injury-induced central sensitization can manifest as an increase in
      excitatory synaptic transmission and/or as a decrease in inhibitory synaptic
      transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis
      factor-alpha (TNF-alpha) are induced in the spinal cord under various injury
      conditions and contribute to neuropathic pain. In this study we examined the
      effect of TNF-alpha in modulating excitatory and inhibitory synaptic input to
      spinal substantia gelatinosa (SG) neurons over time in mice following chronic
      constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp studies
      from SG neurons showed that TNF-alpha enhanced overall excitability of the spinal
      cord early in time following nerve injury 3 days after CCI compared with that in
      sham control mice. In contrast, the effects of TNF were blunted 14 days after CCI
      in nerve-injured mice compared with sham surgery mice. Immunohistochemical
      staining showed that the expression of TNF-alpha receptor 1 (TNFR1) was increased
      at 3 days but decreased at 14 days following CCI in the ipsilateral vs. the
      contralateral spinal cord dorsal horn. These results suggest that TNF-alpha
      acting at TNFR1 is important in the development of neuropathic pain by
      facilitating excitatory synaptic signaling in the acute phases after nerve injury
      but has a reduced effect on spinal neuron signaling in the later phases of nerve
      injury-induced pain. Failure of the facilatory effects of TNF-alpha on excitatory
      synaptic signaling in the dorsal horn to resolve following nerve injury may be an
      important component in the transition between acute and chronic pain conditions. 

PMID- 23864373
TI  - Cav3-type alpha1T calcium channels mediate transient calcium currents that
      regulate repetitive firing in Drosophila antennal lobe PNs.
AB  - Projection neurons (PNs), located in the antennal lobe region of the insect
      brain, play a key role in processing olfactory information. To explore how
      activity is regulated at the level of single PNs within this central circuit we
      have recorded from these neurons in adult Drosophila melanogaster brains. Our
      previous study demonstrated that PNs express voltage-gated calcium currents with
      a transient and sustained component. We found that the sustained component is
      mediated by cac gene-encoded Cav2-type channels involved in regulating action
      potential-independent release of neurotransmitter at excitatory cholinergic
      synapses. The function of the transient calcium current and the gene encoding the
      underlying channels, however, were unknown. Here we report that the transient
      current blocked by prepulse inactivation is sensitive to amiloride, a vertebrate
      Cav3-type channel blocker. In addition PN-specific RNAi knockdown of alpha1T, the
      Drosophila Cav3-type gene, caused a dramatic reduction in the transient current
      without altering the sustained component. These data demonstrate that the alpha1T
      gene encodes voltage-gated calcium channels underlying the amiloride-sensitive
      transient current. Alterations in evoked firing and spontaneous burst firing in
      the alpha1T knockdowns demonstrate that the Cav3-type calcium channels are
      important in regulating excitability in adult PNs. 

PMID- 23864374
TI  - Combination of chondroitinase ABC and AAV-NT3 promotes neural plasticity at
      descending spinal pathways after thoracic contusion in rats.
AB  - Transmission through descending pathways to lumbar motoneurons, although
      important for voluntary walking in humans and rats, has not been fully understood
      at the cellular level in contusion models. Major descending pathways innervating
      lumbar motoneurons include those at corticospinal tract (CST) and ventrolateral
      funiculus (VLF). We examined transmission and plasticity at synaptic pathways
      from dorsal (d)CST and VLF to individual motoneurons located in ventral horn and
      interneurons located in dorsomedial gray matter at lumbar segments after thoracic
      chronic contusion in adult anesthetized rats. To accomplish this, we used
      intracellular electrophysiological recordings and performed acute focal spinal
      lesions during the recordings. We directly demonstrate that after thoracic T10
      chronic contusion the disrupted dCST axons spontaneously form new synaptic
      contacts with individual motoneurons, extending around the contusion cavity,
      through spared ventrolateral white matter. These detour synaptic connections are
      very weak, and strengthening these connections in order to improve function may
      be a target for therapeutic interventions after spinal cord injury (SCI). We
      found that degradation of scar-related chondroitin sulfate proteoglycans with the
      enzyme chondroitinase ABC (ChABC) combined with adeno-associated viral (AAV)
      vector-mediated prolonged delivery of neurotrophin NT-3 (AAV-NT3) strengthened
      these spontaneously formed connections in contused spinal cord. Moreover,
      ChABC/AAV-NT3 treatment induced the appearance of additional detour synaptic
      pathways innervating dorsomedial interneurons. Improved transmission in ChABC/AAV
      NT3-treated animals was associated with increased immunoreactivity of 5-HT
      positive fibers in lumbar dorsal and ventral horns. Improved locomotor function
      assessed with automated CatWalk highlights the physiological significance of
      these novel connections. 

PMID- 23864376
TI  - Sniff rhythm-paced fast and slow gamma-oscillations in the olfactory bulb:
      relation to tufted and mitral cells and behavioral states.
AB  - Odor signals are conveyed from the olfactory bulb (OB) to the olfactory cortex by
      two types of projection neurons, tufted cells and mitral cells, which differ in
      signal timing and firing frequency in response to odor inhalation. Whereas tufted
      cells respond with early-onset high-frequency burst discharges starting at the
      middle of the inhalation phase of sniff, mitral cells show odor responses with
      later-onset lower-frequency burst discharges. Since odor inhalation induces
      prominent gamma-oscillations of local field potentials (LFPs) in the OB during
      the transition period from inhalation to exhalation that accompany synchronized
      spike discharges of tufted cells and mitral cells, we addressed the question of
      whether the odor-induced gamma-oscillations encompass two distinct gamma
      oscillatory sources, tufted cell and mitral cell subsystems, by simultaneously
      recording the sniff rhythms and LFPs in the OB of freely behaving rats. We
      observed that individual sniffs induced nested gamma-oscillations with two
      distinct parts during the inhalation-exhalation transition period: early-onset
      fast gamma-oscillations followed by later-onset slow gamma-oscillations. These
      results suggest that tufted cells carry odor signals with early-onset fast gamma
      synchronization at the early phase of sniff, whereas mitral cells send them with
      later-onset slow gamma-synchronization. We also observed that each sniff
      typically induced both fast and slow gamma-oscillations during awake, whereas
      respiration during slow-wave sleep and rapid-eye-movement sleep failed to induce
      these oscillations. These results suggest that behavioral states regulate the
      generation of sniff rhythm-paced fast and slow gamma-oscillations in the OB. 

PMID- 23864375
TI  - Predicting spike timing in highly synchronous auditory neurons at different sound
      levels.
AB  - A challenge for sensory systems is to encode natural signals that vary in
      amplitude by orders of magnitude. The spike trains of neurons in the auditory
      system must represent the fine temporal structure of sounds despite a tremendous
      variation in sound level in natural environments. It has been shown in vitro that
      the transformation from dynamic signals into precise spike trains can be
      accurately captured by simple integrate-and-fire models. In this work, we show
      that the in vivo responses of cochlear nucleus bushy cells to sounds across a
      wide range of levels can be precisely predicted by deterministic integrate-and
      fire models with adaptive spike threshold. Our model can predict both the spike
      timings and the firing rate in response to novel sounds, across a large input
      level range. A noisy version of the model accounts for the statistical structure
      of spike trains, including the reliability and temporal precision of responses.
      Spike threshold adaptation was critical to ensure that predictions remain
      accurate at different levels. These results confirm that simple integrate-and
      fire models provide an accurate phenomenological account of spike train
      statistics and emphasize the functional relevance of spike threshold adaptation. 

PMID- 23864377
TI  - Strategies to develop putative biomarkers to characterize the female phenotype
      with autism spectrum disorders.
AB  - Current observational inventories used to diagnose autism spectrum disorders
      (ASD) apply similar criteria to females and males alike, despite developmental
      differences between the sexes. Recent work investigating the chronology of
      diagnosis in ASD has raised the concern that females run the risk of receiving a
      delayed diagnosis, potentially missing a window of opportunity for early
      intervention. Here, we retake this issue in the context of the objective
      measurements of natural behaviors that involve decision-making processes. Within
      this context, we quantified movement variability in typically developing (TD)
      individuals and those diagnosed with ASD across different ages. We extracted the
      latencies of the decision movements and velocity-dependent parameters as the hand
      movements unfolded for two movement segments within the reach: movements intended
      toward the target and withdrawing movements that spontaneously, without
      instruction, occurred incidentally. The stochastic signatures of the movement
      decision latencies and the percent of time to maximum speed differed between
      males and females with ASD. This feature was also observed in the empirically
      estimated probability distributions of the maximum speed values, independent of
      limb size. Females with ASD showed different dispersion than males with ASD. The
      distinctions found for females with ASD were better appreciated compared with
      those of TD females. In light of these results, behavioral assessment of autistic
      traits in females should be performed relative to TD females to increase the
      chance of detection. 

PMID- 23864378
TI  - Multichannel brain recordings in behaving Drosophila reveal oscillatory activity
      and local coherence in response to sensory stimulation and circuit activation.
AB  - Neural networks in vertebrates exhibit endogenous oscillations that have been
      associated with functions ranging from sensory processing to locomotion. It
      remains unclear whether oscillations may play a similar role in the insect brain.
      We describe a novel "whole brain" readout for Drosophila melanogaster using a
      simple multichannel recording preparation to study electrical activity across the
      brain of flies exposed to different sensory stimuli. We recorded local field
      potential (LFP) activity from >2,000 registered recording sites across the fly
      brain in >200 wild-type and transgenic animals to uncover specific LFP frequency
      bands that correlate with: 1) brain region; 2) sensory modality (olfactory,
      visual, or mechanosensory); and 3) activity in specific neural circuits. We found
      endogenous and stimulus-specific oscillations throughout the fly brain. Central
      (higher-order) brain regions exhibited sensory modality-specific increases in
      power within narrow frequency bands. Conversely, in sensory brain regions such as
      the optic or antennal lobes, LFP coherence, rather than power, best defined
      sensory responses across modalities. By transiently activating specific circuits
      via expression of TrpA1, we found that several circuits in the fly brain modulate
      LFP power and coherence across brain regions and frequency domains. However,
      activation of a neuromodulatory octopaminergic circuit specifically increased
      neuronal coherence in the optic lobes during visual stimulation while decreasing
      coherence in central brain regions. Our multichannel recording and brain
      registration approach provides an effective way to track activity simultaneously
      across the fly brain in vivo, allowing investigation of functional roles for
      oscillations in processing sensory stimuli and modulating behavior. 

PMID- 23864379
TI  - Responses of central vestibular neurons to sinusoidal yaw rotation in compensated
      macaques after unilateral labyrinthectomy.
AB  - After vestibular labyrinth injury, behavioral measures of vestibular function
      partially recover through the process of vestibular compensation. The present
      study was performed to improve our understanding of the physiology of macaque
      vestibular nucleus neurons in the compensated state (>6 wk) after unilateral
      labyrinthectomy (UL). The responses of neurons to sinusoidal yaw rotation at a
      series of frequencies (0.1-2.0 Hz) and peak velocities (7.5-210 degrees /s) were
      examined to determine how the behavior of these cells differed from those in
      animals with intact labyrinths. The sensitivity of neurons responding to
      ipsilateral rotation (type I) did not differ between the intact and injured sides
      after UL, although this sensitivity was lower bilaterally after lesion than
      before lesion. The sensitivity of neurons that increase firing with contralateral
      rotation (type II) was higher ipsilateral to the UL than before lesion or in the
      nucleus contralateral to the UL. UL did not increase asymmetry in the responses
      of individual type I or II neurons to ipsilateral vs. contralateral rotation, nor
      does it change the power law relationship between neuronal firing and level of
      stimulation. Increased sensitivities of contralesional type I neurons to the
      remaining vestibular nerve input and increased efficacy of inhibitory vestibular
      commissures projecting to the ipsilesional vestibular nucleus appear to be
      responsible for recovery of dynamic function of central vestibular neurons in
      compensated animals. The portion of type I neurons on the ipsilesional side is
      reduced in compensated animals, which likely accounts for the asymmetries in
      vestibular reflexes and perception that characterize vestibular function after
      UL.

PMID- 23864380
TI  - Value of freedom to choose encoded by the human brain.
AB  - Humans and animals value the opportunity to choose by preferring alternatives
      that offer more rather than fewer choices. This preference for choice may arise
      not only from an increased probability of obtaining preferred outcomes but also
      from the freedom it provides. We used human neuroimaging to investigate the
      neural basis of the preference for choice as well as for the items that could be
      chosen. In each trial, participants chose between two options, a monetary amount
      option and a "choice option." The latter consisted of a number that corresponded
      to the number of everyday items participants would subsequently be able to choose
      from. We found that the opportunity to choose from a larger number of items was
      equivalent to greater amounts of money, indicating that participants valued
      having more choice; moreover, participants varied in the degree to which they
      valued having the opportunity to choose, with some valuing it more than the
      increased probability of obtaining preferred items. Neural activations in the mid
      striatum increased with the value of the opportunity to choose. The same region
      also coded the value of the items. Conversely, activation in the dorsolateral
      striatum was not related to the value of the items but was elevated when
      participants were offered more choices, particularly in those participants who
      overvalued the opportunity to choose. These data suggest a functional
      dissociation of value representations within the striatum, with general
      representations in mid striatum and specific representations of the value of
      freedom provided by the opportunity to choose in dorsolateral striatum. 

PMID- 23864382
TI  - Observing motor learning produces somatosensory change.
AB  - Observing the actions of others has been shown to affect motor learning, but does
      it have effects on sensory systems as well? It has been recently shown that motor
      learning that involves actual physical practice is also associated with
      plasticity in the somatosensory system. Here, we assessed the idea that
      observational learning likewise changes somatosensory function. We evaluated
      changes in somatosensory function after human subjects watched videos depicting
      motor learning. Subjects first observed video recordings of reaching movements
      either in a clockwise or counterclockwise force field. They were then trained in
      an actual force-field task that involved a counterclockwise load. Measures of
      somatosensory function were obtained before and after visual observation and also
      following force-field learning. Consistent with previous reports, video
      observation promoted motor learning. We also found that somatosensory function
      was altered following observational learning, both in direction and in magnitude,
      in a manner similar to that which occurs when motor learning is achieved through
      actual physical practice. Observation of the same sequence of movements in a
      randomized order did not result in somatosensory perceptual change. Observational
      learning and real physical practice appear to tap into the same capacity for
      sensory change in that subjects that showed a greater change following
      observational learning showed a reliably smaller change following physical motor
      learning. We conclude that effects of observing motor learning extend beyond the
      boundaries of traditional motor circuits, to include somatosensory
      representations. 

PMID- 23864383
TI  - Shifted encoding strategy in retinal luminance adaptation: from firing rate to
      neural correlation.
AB  - Neuronal responses to prolonged stimulation attenuate over time. Here, we ask a
      fundamental question: is adaptation a simple process for the neural system during
      which sustained input is ignored, or is it actually part of a strategy for the
      neural system to adjust its encoding properties dynamically? After simultaneously
      recording the activities of a group of bullfrog's retinal ganglion cells (dimming
      detectors) in response to sustained dimming stimulation, we applied a combination
      of information analysis approaches to explore the time-dependent nature of
      information encoding during the adaptation. We found that at the early stage of
      the adaptation, the stimulus information was mainly encoded in firing rates,
      whereas at the late stage of the adaptation, it was more encoded in neural
      correlations. Such a transition in encoding properties is not a simple
      consequence of the attenuation of neuronal firing rates, but rather involves an
      active change in the neural correlation strengths, suggesting that it is a
      strategy adopted by the neural system for functional purposes. Our results reveal
      that in encoding a prolonged stimulation, the neural system may utilize
      concerted, but less active, firings of neurons to encode information. 

PMID- 23864381
TI  - Regulation of epileptiform discharges in rat neocortex by HCN channels.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated, nonspecific cation (HCN)
      channels have a well-characterized role in regulation of cellular excitability
      and network activity. The role of these channels in control of epileptiform
      discharges is less thoroughly understood. This is especially pertinent given the
      altered HCN channel expression in epilepsy. We hypothesized that inhibition of
      HCN channels would enhance bicuculline-induced epileptiform discharges. Whole
      cell recordings were obtained from layer (L)2/3 and L5 pyramidal neurons and L1
      and L5 GABAergic interneurons. In the presence of bicuculline (10 MUM), HCN
      channel inhibition with ZD 7288 (20 MUM) significantly increased the magnitude
      (defined as area) of evoked epileptiform events in both L2/3 and L5 neurons. We
      recorded activity associated with epileptiform discharges in L1 and L5
      interneurons to test the hypothesis that HCN channels regulate excitatory
      synaptic inputs differently in interneurons versus pyramidal neurons. HCN channel
      inhibition increased the magnitude of epileptiform events in both L1 and L5
      interneurons. The increased magnitude of epileptiform events in both pyramidal
      cells and interneurons was due to an increase in network activity, since holding
      cells at depolarized potentials under voltage-clamp conditions to minimize HCN
      channel opening did not prevent enhancement in the presence of ZD 7288. In
      neurons recorded with ZD 7288-containing pipettes, bath application of the
      noninactivating inward cationic current (Ih) antagonist still produced increases
      in epileptiform responses. These results show that epileptiform discharges in
      disinhibited rat neocortex are modulated by HCN channels. 

PMID- 23864384
TI  - Vulcaniibacterium tengchongense gen. nov., sp. nov. isolated from a geothermally
      heated soil sample, and reclassification of Lysobacter thermophilus Wei et al.
      2012 as Vulcaniibacterium thermophilum comb. nov.
AB  - A thermotolerant Gram-staining negative and aerobic bacterium, designated strain
      YIM 77520(T), was isolated from a geothermally heated soil sample collected at
      Rehai National Park, Tengchong, Yunnan Province, South-West China. Cells of the
      strain were found to be rod-shaped and colonies were light beige and circular.
      The strain was found to grow in the presence of 0-2 % (w/v) total salts (optimum,
      0 %), at pH 6.0-8.0 (optimum, pH 7.0) and 25-55  degrees C (optimum, 45  degrees
      C). The only quinone detected was Q-8 and the genomic DNA G+C content was
      determined to be 66.9 mol%. The major fatty acids (>10 %) were identified as iso
      C16:0 and iso-C15:0. The phospholipids were found to consist of
      phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, five
      unknown phospholipids and three aminophospholipids. Based on the 16S rRNA gene
      sequence analysis, strain YIM 77520(T) was found to form a cluster with
      Lysobacter thermophilus YIM 77875(T) and showed the highest 16S rRNA gene
      sequence similarity to L. thermophilus YIM 77875(T) (96.0 %). These two strains
      formed a distinct lineage of the family 'Xanthomonadaceae'. On the basis of the
      morphological and chemotaxonomic characteristics, as well as genotypic data, a
      new genus, Vulcaniibacterium gen. nov. is proposed with Vulcaniibacterium
      tengchongense sp. nov. as the type species. The type strain of V. tengchongense
      sp. nov. is strain YIM 77520(T) (=DSM 25623(T) = CCTCC AB 2011152(T)).
      Furthermore we propose that L. thermophilus Wei et al. 2012 is reclassified in
      the new genus as Vulcaniibacterium thermophilum comb. nov. (type strain YIM
      77875(T) = CCTCC AB 2012064(T) = KCTC 32020(T)) based on polyphasic data. 

PMID- 23864385
TI  - Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused
      by a novel NFKBIA mutation, p.Ser36Tyr, presents with mild ectodermal dysplasia
      and non-infectious systemic inflammation.
AB  - PURPOSE: Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is
      characterized by hypohidrosis, dental abnormalities, sparse hair, and
      immunodeficiency. Autosomal dominant (AD)-EDA-ID, caused by a heterozygous
      mutation within NFKBIA, is very rare and its clinical features remain largely
      unknown. This study describes a patient with AD-EDA-ID harboring a novel NFKBIA
      mutation who presented with mild EDA and non-infectious systemic inflammation.
      METHODS: The clinical presentation of an AD-EDA-ID patient was described and
      immunological, genetic, and biochemical analyses were performed, with a focus on
      nuclear factor kappa B (NF-kappaB) activation. RESULTS: The patient presented
      with symptoms of mild EDA-ID, namely sparse hair and hypohidrosis, although a
      skin biopsy confirmed the presence of sweat glands. There were no dental
      abnormalities. The patient also suffered from non-infectious inflammation, which
      responded to systemic corticosteroid therapy; however, the patient remained ill.
      Immunological analyses revealed reduced Toll-like receptor/IL-1 (TLR/IL-1) and
      tumor necrosis factor (TNF) receptor family responses to various stimuli. Genetic
      analysis identified a de novo heterozygous missense mutation, p.Ser36Tyr, in
      NFKBIA, resulting in defective NFKBIA degradation and impaired NF-kappaB
      activation. The patient was diagnosed with AD-EDA-ID and underwent hematopoietic
      stem cell transplantation. Engraftment was successful, with few signs of acute
      graft versus host disease. However, the patient suffered hemolytic anemia and
      thrombocytopenia, and died from a brain hemorrhage due to intractable
      thrombocytopenia. CONCLUSION: AD-EDA-ID patients can present with mild ectodermal
      dysplasia and non-infectious inflammation, rather than with recurrent infections.
      Also, hematopoietic stem cell transplantation for AD-EDA-ID is still a clinical
      challenge.

PMID- 23864386
TI  - Disruption of the transforming growth factor-beta pathway by tolfenamic acid via
      the ERK MAP kinase pathway.
AB  - Transforming growth factor-beta (TGF-beta) modulates diverse cell physiological
      processes and plays a complicated role in tumor development. It has been well
      established that TGF-beta inhibits cell proliferation in normal and early stage
      carcinoma and facilitates tumor metastasis in late-stage carcinoma. Therefore,
      blocking TGF-beta signaling in advanced stage carcinogenesis provides a
      potentially interesting chemotherapeutic strategy. We aimed to determine the
      effect of tolfenamic acid (TA) on TGF-beta-induced protumorigenic activity. Here,
      we demonstrate that TA attenuates tumor-promoting effects of TGF-beta in cancer
      cells. Further observation indicates TA blocks the TGF-beta/Smad pathway, and
      this blockage is mainly attributed to the interference of TGF-beta1-driven
      phosphorylation of Smad2/3. We also show that TA could exert this effect on
      cancer cell lines from several different origins and that TA is much better than
      other non-steroidal anti-inflammatory drugs with respect to inhibition of TGF
      beta1-induced Smad2 phosphorylation. Finally, extracellular signal-regulated
      kinase mitogen-activated protein kinase plays a role in TA-induced suppression of
      Smad2/3 phosphorylation and subsequent nuclear accumulation of Smad2/3 in
      response to TGF-beta1. Our study provides a possible mechanism by which TA
      affects anticancer activity by inhibiting the TGF-beta pathway and sheds light on
      the application of TA for cancer patients. 

PMID- 23864387
TI  - Insulin-like growth factor-I receptor is suppressed through transcriptional
      repression and mRNA destabilization by a novel energy restriction-mimetic agent.
AB  - Insulin-like growth factor-I receptor (IGF-IR) represents one of the major
      targets by which dietary or chemically induced energy restriction mediates
      chemopreventive effects in animal tumor models. However, the mechanism underlying
      this cellular response remains unclear. In the course of investigating the
      suppressive effect of the energy restriction-mimetic agent CG-5 on IGF-IR
      expression in prostate cancer cells, we identified a novel posttranscriptional
      mechanism by which the RNA-binding protein human antigen R (HuR) regulates IGF-IR
      expression through messenger RNA (mRNA) stabilization. Previously, we
      demonstrated that Sp1 and HuR proteins were concomitantly targeted for ubiquitin
      dependent degradation by beta-transducin repeat-containing protein in response to
      CG-5. Although this loss of Sp1 expression contributed to CG-5-mediated IGF-IR
      downregulation, enforced specific protein 1 (Sp1) expression could only partially
      protect cells from the drug effect. The small interfering RNA-mediated silencing
      of HuR suppressed IGF-IR expression by reducing mRNA stability, whereas ectopic
      HuR expression increased IGF-IR mRNA stability and protein expression and, when
      coexpressed with Sp1, blocked CG-5-mediated IGF-IR ablation. RNA pull-down and
      immunoprecipitation analyses indicated that HuR selectively bound to the distal
      region of the IGF-IR 3' untranslated region (UTR), whereas no interaction with
      the 5'UTR was noted. Evaluation of a series of truncated HuR mutants revealed
      that the RNA recognition motifs (RRM2 and RRM3) were involved in IGF-IR 3'UTR
      binding and the consequent increase in IGF-IR mRNA stability. Although these data
      contrast with a previous report that HuR acted as a translation repressor of IGF
      IR mRNA through 5'UTR binding, our finding is consistent with the reported
      oncogenic role of HuR in conferring stability to target mRNAs encoding tumor
      promoting proteins. 

PMID- 23864390
TI  - Synthesis and anticonvulsant and antidepressant activity of 2-(5-bromo-2,3
      dioxoindolin)-N-substituted phenylacetamide derivatives.
AB  - 16 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-substituted phenylacetamide derivatives
      were synthesized. The chemical structures of the compounds were proved by IR, 1H
      NMR, 13C-NMR, Mass spectrometric data and microanalyses. The antidepressant
      activities of the compounds were investigated by Porsolt's behavioural despair
      (the forced swimming test) in mice. 2-(5-bromo-2,3-dioxoi-ndolin-1-yl)-N-(2
      fluorophenyl)acetamide(4f), 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-(3
      chlorophenyl)acetamide(4j), 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-(4
      bromophenyl)acetamide(4m) reduced 54.9-44.6% duration of immobility times at 100
      mg . kg-1 dose level. Anticonvulsant activities were determined by substances
      pentylenetetrazloe(metrazol)(anti-PTZ) test, and neurotoxicities were determined
      by the rotarod toxicity test in mice. 12 synthesized compounds were found
      protective against PTZ at 100 mg ? kg-1 dose level. 

PMID- 23864388
TI  - Are human endogenous retroviruses pathogenic? An approach to testing the
      hypothesis.
AB  - A number of observations have led researchers to postulate that, despite being
      replication-defective, human endogenous retroviruses (HERVs) may have retained
      the potential to cause or contribute to disease. However, mechanisms of HERV
      pathogenicity might differ substantially from those of modern infectious
      retroviruses or of the infectious precursors of HERVs. Therefore, novel pathways
      of HERV involvement in disease pathogenesis should be investigated. Recent
      technological advances in sequencing and bioinformatics are making this task
      increasingly feasible. The accumulating knowledge of HERV biology may also
      facilitate the definition and general acceptance of criteria that establish HERV
      pathogenicity. Here, we explore possible mechanisms whereby HERVs may cause
      disease and examine the evidence that either has been or should be obtained in
      order to decisively address the pathogenic potential of HERVs.

PMID- 23864391
TI  - Comparison of the exposure of glycyrrhizin and its metabolites and the
      pseudoaldosteronism after intravenous administration of alpha- and beta
      glycyrrhizin in rat.
AB  - Glycyrrhizin, the major bioactive component in licorice root extract, exists as 2
      isomers, alpha and beta-glycyrrhizin, and is associated with causing
      pseudoaldosteronism due to its principal metabolites, glycyrrhetinic acid and 3
      monoglucuronyl-glycyrrhetinic acid. The aim of this study was to compare (a) the
      pharmacokinetics of glycyrrhizin and its metabolites in rat after the first and
      last intravenous doses of either alpha- or beta-glycyrrhizin administered once a
      day over 6 days, (b) kidney levels of the metabolites at 24 h after the last dose
      and (c) the urinary cortisol:cortisone ratio (as a biomarker of
      pseudoaldosteronism) in total urine collected for 24 h after the last dose.After
      the first dose, the clearance of glycyrrhizin in rats given alpha-isomer was
      significantly higher than in those given beta-isomer and the AUC0-24 h values of
      glycyrrhizin and the metabolites were all significantly higher in beta group than
      in alpha group. After the last dose, the AUC0-24 h values of glycyrrhizin and its
      metabolites were again significantly higher in rats given beta-isomer than those
      given alpha-isomer and were all higher than the corresponding values after the
      first dose. Moreover, only kidney levels of glycyrrhetinic acid were detected in
      beta group. The urinary cortisol:cortisone ratio was higher in rats given beta
      isomer and the correlation coefficients of the ratios with the AUC0-24 h values
      of 2 metabolites were 0.81 and 0.89 respectively.The results of the present study
      indicate that alpha-glycyrrhizin is a safer drug than beta- glycyrrhizin probably
      due to a lower systemic exposure to the 2 metabolites.

PMID- 23864392
TI  - The new oral anticoagulants: results of clinical trials and practical
      applications.

PMID- 23864393
TI  - How preconditioning affects the measurement of poro-viscoelastic mechanical
      properties in biological tissues.
AB  - It is known that initial loading curves of soft biological tissues are
      substantially different from subsequent loadings. The later loading curves are
      generally used for assessing the mechanical properties of a tissue, and the first
      loading cycles, referred to as preconditioning, are omitted. However, slow
      viscoelastic phenomena related to fluid flow or collagen viscoelasticity are
      initiated during these first preconditioning loading cycles and may persist
      during the actual data collection. When these data are subsequently used for
      fitting of material properties, the viscoelastic phenomena that occurred during
      the initial cycles are not accounted for. The aim of the present study is to
      explore whether the above phenomena are significant for articular cartilage, by
      evaluating the effect of such time-dependent phenomena by means of computational
      modeling. Results show that under indentation, collagen viscoelasticity dominates
      the time-dependent behavior. Under UC, fluid-dependent effects are more
      important. Interestingly, viscoelastic and poroelastic effects may act in
      opposite directions and may cancel each other out in a stress-strain curve.
      Therefore, equilibrium may be apparent in a stress-strain relationship, even
      though internally the tissue is not in equilibrium. Also, the time-dependent
      effects of viscoelasticity and poroelasticity may reinforce each other, resulting
      in a sustained effect that lasts longer than suggested by their individual
      effects. Finally, the results illustrate that data collected from a mechanical
      test may depend on the preconditioning protocol. In conclusion, preconditioning
      influences the mechanical response of articular cartilage significantly and
      therefore cannot be neglected when determining the mechanical properties. To
      determine the full viscoelastic and poroelastic properties of articular cartilage
      requires fitting to both preconditioning and post-preconditioned loading cycles. 

PMID- 23864395
TI  - Combining NHC-Cu and Bronsted base catalysis: enantioselective allylic
      substitution/conjugate additions with alkynylaluminum reagents and stereospecific
      isomerization of the products to trisubstituted allenes.
AB  - All-catalytic route to trisubstituted allenes: The first examples of catalytic
      enantioselective allylic substitution reactions that involve alkyne-based
      nucleophiles and lead to products having tertiary stereogenic centers are
      followed by an exceptionally stereospecific amine-catalyzed isomerization to
      trisubstituted allenes (see picture; NHC = N-heterocyclic carbene).

PMID- 23864396
TI  - Brain white matter diffusion tensor metrics from clinical 1.5T MRI distinguish
      between ALS phenotypes.
AB  - Patients with amyotrophic lateral sclerosis (ALS) can present with varying
      degrees of upper motor neuron (UMN) and lower motor neuron dysfunction. Previous
      diffusion tensor imaging (DTI) studies, in which ALS patients were not separated
      by the degree of UMN dysfunction, have resulted in conflicting or inconclusive
      results. We hypothesized that (1) categorizing ALS patients by their clinical
      phenotype can reveal differences in DTI abnormalities along the corticospinal
      tract (CST), and (2) data obtained from routine clinical DTI scans can provide
      this type of information. Clinical DTI scans were obtained at 1.5T in 87 ALS
      patients (categorized into four subgroups based on clinical phenotype) and in 12
      neurologic controls. Fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD) and radial diffusivity values from the CST were compared between
      ALS subgroups and controls. Significantly reduced FA and elevated MD values were
      observed in ALS patients compared to controls at the subcortical motor cortex
      level. Significant differences in AD values were not only seen between control
      and ALS patients but also between the ALS subgroups, suggesting divergent
      pathologies in these ALS patients. Classifying ALS patients by phenotype reveals
      differences in CST abnormalities between subgroups and may provide novel insights
      into disease mechanisms. The close similarity of our results from routine
      clinical scans with published research studies suggests wider accessibility to
      useful DTI metrics.

PMID- 23864397
TI  - Kurt Goldstein (1878-1965).

PMID- 23864399
TI  - Effectiveness of C5 or C6-Cz assembly in predicting immediate post operative
      facial nerve deficit.
AB  - BACKGROUND: Intraoperative neurophysiology monitoring (IOM) is a valuable tool in
      cerebellopontine angle (CPA) surgeries posing risk to the cranial nerves.
      Transcranial electrical stimulation (TES) for cranial nerves has been performed
      in the last 7 years, for obtaining the facial nerve motor evoked potential (MEP),
      using either C3/C4-Cz or C3-C4 (or inverse) stimulating points, which have been
      correlated with facial nerve functional outcome. METHOD: Intraoperative surgical
      and electrophysiological findings were documented prospectively. Patient files
      were reviewed for clinical data. We studied 23 patients undergoing CPA tumor
      resection using C5 or C6-Cz montage for TES, and were able to determine the
      correlation between facial nerve functional outcome and the amplitude drop of
      facial MEP above 50 %. Patients were evaluated for immediate facial nerve outcome
      and 6 months after the surgery. Follow-up was performed by structured telephone
      interviews with local physicians. RESULTS: The sensibility of the studied
      parameters was 92.8 % for amplitude drop of facial nerve MEP, with positive
      predictive value of 81.2 %. The absence of changes during IOM has shown a
      negative predictive value of 100 %. CONCLUSION: In this series, the used montage
      was effective in predicting new facial deficit.

PMID- 23864398
TI  - Obstetrical epidural and spinal anesthesia in multiple sclerosis.
AB  - To examine obstetrical epidural and spinal anesthesia use in women with multiple
      sclerosis (MS) and the relationship with MS clinical factors. This was a
      retrospective cohort study, linking clinical data from women with MS in the
      British Columbia (BC) MS database to obstetrical data (1998-2009) from the BC
      Perinatal Database Registry. We compared epidural use in 431 deliveries to women
      with MS and 2,959 deliveries from the general population, as well as spinal use
      in cesarean deliveries (128 to women with MS and 846 in the general population),
      considering parity and using multivariate models. We also examined the
      association between epidural or spinal anesthesia and MS clinical factors-disease
      duration and disability [Expanded Disability Status Scale (EDSS) score]. Of 431
      deliveries to women with MS, 116 were exposed to epidural anesthesia and of 128
      cesarean deliveries, 82 were exposed to spinal anesthesia. The use of epidural
      anesthesia was similar in nullipara (adjusted OR = 0.86, 95 % CI = 0.63-1.18, p =
      0.36), but more likely in multipara with MS (adjusted OR = 1.75, 95 % CI = 1.20
      2.54, p = 0.004). Spinal anesthesia use in cesarean deliveries was comparable
      between the MS and general population cohorts (adjusted OR = 0.84, 95 % CI = 0.55
      1.31, p = 0.45). Women who delivered 5 to <10 years after MS onset were less
      likely to have an epidural (adjusted OR = 0.57, 95 % CI = 0.34-0.95, p = 0.03)
      vs. those delivering within 5 years. EDSS was not associated with use of either
      type of anesthesia (adjusted p > 0.1). Contrary to previous studies, epidural
      anesthesia use differed between women with MS and the general population and was
      influenced by parity and MS disease duration; these findings warrant further
      investigation.

PMID- 23864400
TI  - Resting perfusion MPI-SPECT combined with cardiac 123I-mIBG sympathetic
      innervation imaging improves prediction of arrhythmic events in non-ischemic
      cardiomyopathy patients: sub-study from the ADMIRE-HF trial.
AB  - BACKGROUND: Delayed Iodine-123 meta-iodobenzylguanidine heart/mediastinum (H/M)
      uptake ratio predicted arrhythmic events in patients with heart failure (HF) and
      significant left ventricular dysfunction in ADMIRE-HF. We tested the hypothesis
      that resting perfusion defects on MPI-SPECT, representing scar, would further
      risk stratify patients beyond H/M ratio in the prediction of ventricular
      arrhythmic events in both ischemic (ICM) and non-ischemic cardiomyopathy (NICM)
      patients. METHODS: Patients from the ADMIRE-HF database were classified as ICM
      and NICM and were stratified by delayed H/M ratio (<1.6/>=1.6) and by summed rest
      score (SRS) (<=8/>8) on MPI-SPECT. The entire cohort was also classified as high
      risk (H/M <1.6, SRS >8) and low risk (H/M >=1.6, SRS <=8). Scores were from
      visual interpretation of individual and derived consensus (average) reads per
      ASNC guidelines. RESULTS: There were 612 (66%) ICM and 317 (34%) NICM patients.
      ICM patients had higher mean SRS than NICM patients (25 +/- 13 vs 12 +/- 10).
      Sixty-three arrhythmic events occurred over a median follow-up of 17 months. SRS
      had incremental predictive value among NICM patients with low H/M ratio (<1.6).
      There was no risk stratification in patients with ICM. Multivariable analysis for
      NICM with H/M ratio <1.6 demonstrated SRS score >8 as the only independent
      predictor of arrhythmic events (hazard ratio 3.3, 95% CI 1.1-9.8, P = .03).
      Patients classified in high-risk subgroup had statistically significant increased
      risk of arrhythmic events (hazard ratio 2.080, 95% CI 1.112-3.894, P = .022).
      There was only one event in low-risk subgroup with a trend towards lower risk of
      arrhythmic events (P = .07). CONCLUSION: Resting perfusion defects provide
      independent risk stratification in addition to Iodine-123 meta
      iodobenzylguanidine sympathetic innervation imaging in predicting arrhythmic
      events in patients with NICM and HF. High and potentially low-risk groups for
      arrhythmic events can be identified based on the severity of resting perfusion
      defect score and H/M ratio.

PMID- 23864401
TI  - Is reading sexual intention truly functional? The impact of perceiving a
      partner's sexual intention on courtship initiation behaviors.
AB  - The present research examined the presumed but not tested behavioral functions of
      sexual intent perception. Sex differences in the perception of a partner's sexual
      intention have been explained by its functions, from an evolutionary perspective,
      in males' and females' divergent mating goals. Our research directly explored the
      functional explanation in terms of behavioral impact by testing whether sex
      differences in sexual intent perception could lead to successful courtship
      behaviors. In Study 1, 411 college students reported their preferred courtship
      initiating behaviors in hypothetical situations in which their own sexual
      motivation and their perceptions of a potential partner's sexual intention
      varied. The results showed that females' courtship behaviors were influenced only
      by their own sexual motivation whereas males' behaviors were influenced by both
      their own sexual motivation and their perception of a potential partner's sexual
      intent. Study 2 examined whether a participant's perception of a potential
      partner's sexual intention resulted in the participant selecting the specific
      courtship strategies that could eventually lead to successful mating
      opportunities. We compared the behavioral strategies preferred by courtship
      initiators (Study 1) to the reactions of courtship targets toward these same
      strategies (collected from 103 college students in Study 2) when the target's
      sexual intention and the initiator's perception of it matched. The results showed
      that only one condition-male initiators whose perception of the target's sexual
      intent corresponded with the target's actual intent-utilized effective courtship
      behaviors. The findings were consistent with the functional prediction and their
      theoretical implications for the evolutionary perspective were discussed.

PMID- 23864402
TI  - Traits of autism spectrum disorders in adults with gender dysphoria.
AB  - The literature examining the co-occurrence of gender dysphoria (GD) and autistic
      traits has so far been limited to a series of small case studies and two
      systematic studies, one looking at autistic traits in gender dysphoric children
      and the other set within the context of the extreme male brain hypothesis and
      looking at adults. The current study examined this co-occurrence of GD and
      autistic traits in an adult population, to see whether this heightened prevalence
      persisted from childhood as well as to provide further comparison of MtF versus
      FtM transsexuals and homosexual versus nonhomosexual individuals. Using the
      Autistic Spectrum Quotient (AQ), 91 GD adults (63 male-to-female [MtF] and 28
      female-to-male [FtM]) undertaking treatment at a gender clinic completed the AQ.
      The prevalence of autistic traits consistent with a clinical diagnosis for an
      autism spectrum disorder (ASD) was 5.5 % (n = 3 MtF and n = 2 FtM) compared to
      reports of clinical diagnoses of 0.5-2.0 % in the general population. In contrast
      to the single previous report in adults, there was no significant difference
      between MtF and FtM on AQ scores; however, all of those who scored above the
      clinical cut-off were classified as nonhomosexual with respect to natal sex.
      Results were considered in the context of emerging theories for the observed co
      occurrence of GD and autistic traits.

PMID- 23864404
TI  - Trends in US newspaper and television coverage of tobacco.
AB  - PURPOSE: The news media plays an important role in agenda setting and framing of
      stories about tobacco control. The purpose of this study was to examine
      newspaper, newswire and television coverage of tobacco issues in the USA over a 7
      year period. METHODS: Analyses of 2004-2010 news media surveillance system data
      from the US Centers for Disease Control and Prevention's Office on Smoking and
      Health, based on content analysis and quantitative methods. Information on extent
      of news coverage, and types of tobacco-related themes, were examined from
      articles in 10 newspapers and 2 major newswires, as well as transcripts from 6
      national television networks. RESULTS: The overall extent of newspaper, newswire
      and television stories about tobacco, and level of coverage by specific media
      outlets, varied over time, especially for newspapers. Nevertheless, there was an
      average of 3 newspaper stories, 4 newswire stories, and 1 television tobacco
      related story each day. Television stories were more likely to contain
      cessation/addiction or health effects/statistics themes and less likely to
      contain secondhand smoke or policy/regulation themes than newspaper/newswire
      stories. There was more variation in the choice of tobacco theme among individual
      newspapers/newswires than television media outlets. CONCLUSIONS: News coverage of
      tobacco in the USA was relatively constant from 2004 to 2010. Audiences were more
      likely to be exposed to different tobacco themes in newspapers/newswires than on
      television. Tracking information about tobacco news stories can be used by
      advocates, programs and others for planning and evaluation, and by researchers
      for hypothesis generation.

PMID- 23864403
TI  - Mediators of a culturally-sensitive intervention for suicidal African American
      women.
AB  - This study explored intervention outcomes and mechanisms that could help explain
      why low-income, African American women with a history of intimate partner abuse
      and suicide attempt improve in response to a culturally-informed intervention,
      the Grady Nia Project. Specifically, the investigation examined whether or not
      the intervention had effects on the women and whether or not spiritual well-being
      and coping mediated the effects of the intervention on suicidal ideation and
      depressive symptoms. In this randomized controlled clinical trial, data from 89
      women who completed both pre- and post-intervention assessments were analyzed.
      During the post-intervention follow-up, women in the active intervention group
      reported lower levels of suicidal ideation and depressive symptoms and higher
      levels of existential well-being and adaptive coping skills than those women
      randomized to the treatment as usual group. However, only existential well-being
      was found to mediate treatment effects on suicidal ideation and depressive
      symptoms. Religious well-being, as well as adaptive and maladaptive coping, did
      not serve a mediational function. These findings highlight the importance of
      designing and implementing culturally-sensitive and evidence-based strategies
      that enhance existential well-being in this population.

PMID- 23864406
TI  - [The life stages of the (trainee) psychiatrist].

PMID- 23864405
TI  - Early diagnosis of tuberculous meningitis by an indirect ELISA protocol based on
      the detection of the antigen ESAT-6 in cerebrospinal fluid.
AB  - BACKGROUND: Early diagnosis of tuberculous meningitis (TBM) is still a challenge;
      the present study aimed to establish a method of detecting the antigen early
      secreted antigenic target 6 (ESAT-6) in cerebrospinal fluid (CSF) by an indirect
      enzyme-linked immunosorbance assay (ELISA) protocol and to study the value of
      detecting ESAT-6 in CSF in the early diagnosis of TBM. METHODS: An indirect ELISA
      protocol was used, employing a monoclonal antibody (mAb) against ESAT-6, which
      was used to demonstrate ESAT-6 in the CSF from TBM patients and non-TBM controls.
      CSF was obtained from 100 patients: confirmed TBM, clinically diagnosed TBM,
      disease controls, and healthy controls (n = 10). Pure recombinant ESAT-6
      (standard product) was used in serial dilutions to detect the absorbance and to
      establish a standard curve from the data; the concentration was on the X axis vs.
      absorbance on the Y axis, and the standard curve was used to interpolate the
      concentration of ESAT-6 in samples. RESULTS: The indirect ELISA method provided
      88 % sensitivity and 92 % specificity for the diagnosis of TBM using a mAb to
      ESAT-6. The mean concentration of ESAT-6 in TBM patients was significantly higher
      than that of the non-TBM groups. There was also a significant difference in the
      mean ESAT-6 expression between the confirmed TBM patients and the clinically
      diagnosed TBM patients (p < 0.01). CONCLUSIONS: Detection of ESAT-6 in the CSF of
      TBM patients by indirect ELISA protocol gives a reliable early diagnosis and can
      be used to develop an immunodiagnostic assay with increased sensitivity and
      specificity.

PMID- 23864407
TI  - [Which characteristics of adolescents with behavioural problems are associated
      with the completion of residential treatment].
AB  - BACKGROUND: Many adolescents who have a combination of psychiatric disorders and
      behavioural problems fail to complete their course of treatment and therefore do
      not get the treatment they need. AIM: To investigate whether gender and the
      severity of symptoms at the start of treatment can predict whether patients will
      complete their course of treatment. METHOD: By means of questionnaires ( SCL-90,
      YSR and CBCL) we attempted to find out if the gender and symptoms of 127 male
      adolescent patients beginning their treatment in a psychiatric institution could
      'predict' whether the patients would complete their treatment or terminate it
      prematurely. For the purpose of our research, specific definitions of the terms
      drop out, push out and treatment success were formulated. RESULTS: The inter
      rater reliability of the definitions of drop out and treatment success ranged
      from adequate to good, whereas the reliability of the definition of push out was
      only moderate. CONCLUSION: The questionnaire was not able to predict accurately
      whether patients would complete their treatment. Apparently, adolescent males
      whose treatment was predicted to have a more favourable outcome had obtained
      higher scores on the ( SCL-90) Hostility subscale at the beginning of treatment
      and more girls than boys were judged to have improved.

PMID- 23864408
TI  - [Mission statements of Dutch mental health institutions; the quality of
      communication with stakeholders].
AB  - BACKGROUND: As a result of recent reforms in Dutch health care, healthcare
      providers are having to operate more and more like commercial organisations and
      adopt some of the rules prevailing in the profit sector. Because missions
      statements can be an efficient means of useful communication with internal and
      external stakeholders they can make a useful contribution to the way healthcare
      institutions are managed and to their status and reputation. Research shows that
      in view of this the quality of the messages conveyed via mission statements is
      important. AIM: To ascertain which stakeholders are mentioned in the mission
      statements of Dutch mental healthcare providers and to quantify the quality of
      the messages conveyed to them via mission statements. METHOD: We examined the
      mission statements of 34 mental health providers to find out which stakeholders
      were included. The message conveyed to the stakeholders was quantified by means
      of a validated measuring instrument devised specifically for this purpose.
      RESULTS: Patients were referred to in all mission statements and the quality of
      the messages conveyed was of higher quality than the messages conveyed to other
      stakeholders. Other important stakeholders on whom the institutions depended were
      referred to much less frequently and the quality of sections of text referring to
      them was definitely inferior. CONCLUSION: Mission statements frequently serve as
      management tool for Dutch mental healthcare providers. The potential benefits
      that these statements could bestow on the providers are not being fully exploited
      because the standard of communication with several internal and external
      stakeholders is of poor quality.

PMID- 23864409
TI  - [The nicotine receptor as target for the improvement of cognitive symptoms in
      schizophrenia].
AB  - BACKGROUND: Nicotine receptor agonists are drugs that may be useful for the
      treatment of cognitive symptoms in schizophrenia. AIM: By studying the relevant
      literature we want to investigate to what extent nicotine enhances cognition in
      patients with schizophrenia and to find out which domains are affected. We also
      attempt to identify the obstacles that might impede the use, in the future, of
      nicotine receptor agonists. In addition, we aim to present the most likely
      neurobiological working mechanism of nicotine. METHOD: We searched the literature
      using PubMed and the search terms &lsquo;schizophrenia&rsquo;,
      (&lsquo;nicotine&rsquo; or &lsquo;smoking&rsquo;), &lsquo;cognition&rsquo; and
      &lsquo;P50&rsquo;. RESULTS: Attention and visuo-spatial memory seems to respond
      favourably to once-only stimulation by nicotine. These results are supported both
      by the improvement that nicotine brought about in the signal-to-noise ratio in a
      P50 sensory grating paradigm and by the neurobiological findings. However, the
      effect of chronic nicotinergic stimulation is less clear. CONCLUSION: There is
      some evidence that nicotine does have a mild but acute cognition-enhancing effect
      in patients with schizophrenia. However, nicotine is not suitable for clinical
      use, because it can have side effects and lead to addiction and desensitisation
      of the nicotine receptor. Nevertheless, nicotine receptor agonists do have the
      potential to enhance and stimulate cognition.

PMID- 23864410
TI  - [Consensus regarding the definition of persons with severe mental illness and the
      number of such persons in the Netherlands].
AB  - BACKGROUND: Insurance companies and mental health service planners need to have
      information about the prevalence of severe mental illness (SMI) and about the
      numbers of persons affected. They require these data in order to be able to
      develop, implement and evaluate innovative mental health care for such patients.
      This information lets them draw up their budgets and define their priorities.
      AIM: To reach a consensus regarding the number of patients with SMI in the
      Netherlands. METHOD: A consensus was reached regarding the definition of SMI, and
      the prevalence of SMI was determined on the basis of epidemiological literature
      and policy papers relating to mental health care in the Netherlands. When figures
      from the literature were inaccurate or unavailable, estimates were checked by a
      group of experts. RESULTS: The definition of SMI was adjusted and amended in
      relation to psychiatric comorbidity. An analysis of the care-loads of all the
      mental health care providers yielded an estimate of 160,000 SMI patients aged 18
      65, including those receiving addiction care and forensic care (1.6% of the adult
      population). When children and adolescents (< 18 years) and the elderly (> 65
      years) were included, the total number of patients came to 216,000 (1.3%). The
      prevalence among the population was estimated to be 281,000 (1.7%). CONCLUSION:
      The Consensus group is of the opinion that the consensus document estimates of
      the number of SMI patients in the Netherlands are as accurate as they can
      possibly be. Of course, the document contains assumptions and extrapolations
      which will require further research. The figures will be confirmed or adjusted in
      the future as soon as new evidence becomes available.

PMID- 23864411
TI  - [The need to monitor risk factors relating to patients on antipsychotics].
AB  - BACKGROUND: The use of antipsychotics can lead to the development of obesity,
      dyslipidemia, hypertension and hyperglycemia, risk factors for diabetes mellitus
      type 2 and cardiovascular diseases. AIM: To find out whether patients suffering
      from psychoses and schizophrenia and taking antipsychotics should be monitored
      systematically and periodically for the risk factors for and complications of the
      above-mentioned diseases. METHOD: A written survey was conducted among the
      relatives of users of antipsychotics, relatives being members of the Ypsilon
      association in the Limburg region. RESULTS: Seventy-eight relatives (27%)
      returned the forms. Compared to the Dutch population, the risk factor for high
      blood pressure was remarkably common in the 20-30 age group. In the group of
      persons aged 30-40 obesity occurred surprisingly frequently; remarkably frequent
      too was diabetes in the 40-50 age group. At each monitoring session 27% of the
      users were checked on all parameters. Only 59% of the users were checked
      periodically. CONCLUSION: Apparently, systematic and regular monitoring of risk
      factors and somatic complications is currently inadequate. The regional survey
      therefore needs to be extended so that it covers the entire country.

PMID- 23864412
TI  - [A psychiatrist is not always the one and only specialist needed by patients with
      psychiatric symptoms].
AB  - We present three cases in which psychiatric symptoms were misinterpreted and
      somatic investigation was incomplete. Some of the symptoms encountered in mental
      health care such as anxiety, confusion and even attempted suicide, are caused by
      an underlying somatic disorder. In most cases, particularly when patients have a
      known past psychiatric history, insufficient attention is given to possible
      somatic causes of psychiatric symptoms. Since psychiatric and somatic symptoms
      can clearly overlap, we believe that health professionals, particularly
      psychiatrists, should take a broad clinical view and give close attention to the
      possibility that a patient&rsquo;s psychiatric symptoms may have somatic causes. 

PMID- 23864413
TI  - [Letter to Wim van der Meeren, chairman CZ; Clients of CZ refuse to submit data
      to Stichting Benchmark GGz].

PMID- 23864414
TI  - [Reaction on 'Current routine outcome monitoring undermines valid quality
      measurement'].

PMID- 23864415
TI  - Predictors of Gleason score upgrading in a large African-American population.
AB  - PURPOSE: Gleason score from biopsy specimens is important for prostate cancer
      (PCa) risk stratification and influences treatment decisions. Gleason score
      upgrading (GSU) between biopsy and surgical pathology specimens has been reported
      as high as 50 % and presents a challenge in counseling low-risk patients. While
      recent studies have investigated predictors of GSU, populations in these studies
      have been largely Caucasian. We report our analysis of predictors of GSU in a
      large urban African-American population. METHODS: A total of 959 patients with
      D'Amico low-risk prostate cancer underwent radical prostatectomy at Georgetown
      University or Washington Hospital Center between January 2005 and July 2012.
      Race, age, PSA, body mass index (BMI), cancer of the prostate risk assessment
      (CAPRA) score, and transrectal ultrasound (TRUS) biopsy characteristics (percent
      of biopsy cores showing adenocarcinoma, highest percent of biopsy core involved
      with cancer, and measured TRUS prostate volume) were analyzed with both
      univariate and multivariate analyses to identify significant predictors of GSU
      while controlling for clinical parameters. RESULTS: Of the 959 cases, 288 (30.0
      %) were upgraded on final pathologic specimen with approximately 38 % (133/355)
      of African-American patients experiencing GSU. BMI (P = 0.02), percent positive
      biopsy cores (P < 0.01) and percent of core involved with cancer (P < 0.01),
      increasing CAPRA score, and serum PSA were independent predictors of GSU on both
      uni- and multivariate regression analyses. African Americans had a 73 % increase
      in the incidence of GSU over other races. CONCLUSION: More than a quarter of low
      risk prostate cancer patients were upgraded on final pathology in our series.
      Higher BMI, serum PSA, CAPRA score, percent of cores positive, and percent of
      cores involved were independent predictors of GSU. Individuals with those
      clinical parameters may harbor occult high-grade disease and should be carefully
      counseled on treatment decisions.

PMID- 23864416
TI  - Clinical outcomes of augmentation cystoplasty in patients suffering from ketamine
      related bladder contractures.
AB  - OBJECTIVE: To evaluate the outcomes of augmentation cystoplasty in patients with
      bladder contractures secondary to chronic ketamine abuse. METHOD: Patients who
      had received augmentation cystoplasty to treat ketamine-related bladder
      contractures in two hospitals in our region were reviewed retrospectively. Their
      history of ketamine consumption, presenting symptoms, history of treatment,
      surgical information and post-operative conditions were retrieved from clinical
      records and then summarized. RESULTS: Between 2006 and 2011, four patients (three
      women and one man), aged 21-30 years (mean 27 years), underwent augmentation
      cystoplasty for ketamine-related bladder contractures. The duration of ketamine
      consumption ranged from 3 to 15 years, and all four patients resumed ketamine
      consumption after surgery. The mean maximal baseline and post-operative bladder
      capacity was 37.5 cc (range 25-50 cc) and up to 400-500 cc, respectively. Three
      patients experienced a further deterioration in renal function that was secondary
      to new-onset ureteral strictures in two cases and to sepsis in the other. At the
      time of the last follow-up, three patients could void spontaneously and one
      required regular intermittent catheterization. CONCLUSION: Ketamine cystitis is
      an emerging medical condition that requires a multi-disciplinary approach to
      manage the patients. Simple surgical management of the physical component of the
      contracted bladder may produce only suboptimal results, and could even cause
      further problems in some patients. The importance of compliance with post
      operative care and abstinence from drug use should be stressed to the patients
      before surgery. In view of the high complication rate, the option of a simple
      ileal conduit should also be discussed prior to surgical intervention.

PMID- 23864417
TI  - Pharmacokinetic analysis of piperacillin administered with tazobactam in
      critically ill, morbidly obese surgical patients.
AB  - STUDY OBJECTIVE: To evaluate the steady-state pharmacokinetic and pharmacodynamic
      parameters of piperacillin in morbidly obese, surgical intensive care patients.
      DESIGN: Open-label single-center prospective study. SETTING: Level I trauma
      center and university-affiliated teaching institution. PATIENTS: Nine morbidly
      obese (body mass index [BMI] 40.0 kg/m2 or higher) hospitalized patients admitted
      to the trauma and surgical intensive care service who were treated with
      piperacillin-tazobactam between December 15, 2010, and April 18, 2012.
      INTERVENTION: Patients received intravenous piperacillin-tazobactam 4.5 g every 6
      hours, administered as a 30-minute infusion. MEASUREMENTS AND MAIN RESULTS:
      Patients' blood samples were collected after the administration of the fourth,
      fifth, or sixth dose (i.e., at steady state). Serum piperacillin concentrations
      were determined by using a validated high-performance liquid chromatography
      assay; these concentrations were used to estimate pharmacokinetic parameters, and
      5000-patient Monte Carlo simulations were performed. The probability of target
      attainment for 50% or higher of the dosing interval during which free (unbound)
      drug concentrations exceeded the minimum inhibitory concentration (%fT > MIC) of
      likely pathogens was calculated for piperacillin at various MICs. Patient
      demographic and clinical characteristics included a mean +/- SD total body weight
      of 164 +/- 50 kg, BMI of 57 +/- 15.3 kg/m2, and age 57 +/- 11 years, and a median
      Acute Physiology and Chronic Health Evaluation II score of 22 (interquartile
      range 21-26). Compared with values previously reported in other populations, the
      volume of distribution was increased in the study patients, and total system
      clearance was decreased. The net result was a mean +/- SD half-life of 3.7 +/-
      1.2 hours compared with ~1 hour reported in other populations. This contributed
      to an extended %fT > MIC for likely pathogens. Results from all nine patients
      showed %fT > MIC of 100% at the susceptibility breakpoint MIC of 16 mg/L and 85%
      or higher at an MIC of 32 mg/L. CONCLUSION: The pharmacokinetics of piperacillin
      is altered in morbidly obese, surgical intensive care patients. The use of
      standard-dosage piperacillin-tazobactam 4.5 g intravenously every 6 hours was
      shown to be an appropriate dosage for this study population.

PMID- 23864418
TI  - Regulatory effect of stems on sucrose-induced chlorophyll degradation and
      anthocyanin synthesis in Egeria densa leaves.
AB  - Detached green leaves of the aquatic plant Egeria densa showed chlorophyll
      degradation and turned red due to induced anthocyanin synthesis incubated in 0.1
      M sucrose under continuous light for 7-10 days. If the leaves were placed in
      water, only chlorophyll degradation occurred and the detached leaves turned
      yellow. The levels of endogenous total carbohydrates increased in detached leaves
      cultured in the sucrose solution but only increased marginally in water. If the
      leaves were still attached to a piece of stem, with a node on either side of the
      single leaf whorl, then they did not accumulate anthocyanin in culture with 0.1 M
      sucrose. These leaves showed a similar increase in total carbohydrates and
      degradation of chlorophyll as detached leaves. Attached leaves, in which the
      midrib had been cut in situ, showed localized accumulation of anthocyanin in the
      leaf tissue distal to the cut in the midrib when cultured in 0.1 M sucrose. These
      results suggest that the stem plays a regulatory role in anthocyanin synthesis in
      attached leaves cultured in a sucrose solution but does not influence chlorophyll
      degradation or carbohydrate accumulation. 

PMID- 23864419
TI  - Effective policy mechanisms for an equitable geographical distribution of general
      practitioners: a qualitative comparative analysis of the accessibility of primary
      care in Europe.
AB  - OBJECTIVES: To explore the effectiveness of four different policy mechanisms in
      achieving a more equitable geographical distribution of general practitioners
      (GPs) in European countries. The following mechanisms were analysed: (1)
      interventions during medical training; (2) financial incentives; (3) quotas to
      allocate GPs to regions and (4) capitation-based remuneration. METHODS: A macro
      comparative method, namely, fuzzy set qualitative comparative analysis, was
      employed to explore the distributional effectiveness of the four mechanisms. A
      literature review yielded information on the use of these mechanisms in the 21
      European countries included, while country-specific equity in the geographic GP
      distribution served as the outcome variable. RESULTS: Quotas determining the
      number of GPs per region proved to be highly effective in producing an equitable
      GP distribution if calculated based on health care needs. Remunerating GPs
      largely through capitation payments also proved to be an effective policy
      mechanism. Financial bonuses to GPs practising in under-served areas and
      interventions during medical training had little or no impact. CONCLUSION:
      Several high income countries have a maldistribution of primary care physicians
      to the detriment of rural or socially deprived areas. Policy makers have
      instituted a variety of policies to counter this. This study helps to identify
      mechanisms which are likely to be more and less effective.

PMID- 23864420
TI  - Patients' and carers' views on communication and information provision when
      undergoing assessments in memory services.
AB  - OBJECTIVES: To explore patients' and carers' views on what constitutes high
      quality communication and information provision during diagnostic assessment in
      memory clinic services in three areas of England. METHODS: Interviews with 27
      people with cognitive impairment (13 with confirmed dementia) and 26 carers (20
      matched pairs). Interviews continued until theoretical saturation was reached.
      Interview transcripts were subject to constant comparative analysis; data
      interpretation occurred in 'data clinics'. RESULTS: People with memory problems
      undergoing assessment often have unmet information needs, especially patients
      with a diagnosis other than Alzheimer's disease and those who do not receive a
      diagnosis. Patients wish to be kept informed about both the assessment and its
      outcomes. Some have unrealistic expectations of the process (expecting assessment
      and diagnosis to be complete in two weeks) and some experience what appear to be
      long delays (over 12 months) in receiving results. Most appreciated clear and
      honest communication about any diagnosis. Post-diagnostic groups, organized by
      local memory services, afford opportunities to learn practical strategies and
      gain informal peer support. Voluntary organizations may be an essential source of
      information. CONCLUSIONS: Communication and information need improvement for
      patients undergoing assessment for possible dementia, especially for those
      considered unlikely to benefit from medication and those with mild cognitive
      impairment.

PMID- 23864421
TI  - Development and implementation of a nurse-led walk-in centre: evidence lost in
      translation?
AB  - OBJECTIVES: The design of the first Australian public nurse-led primary care walk
      in centre was modelled on those established in the English National Health
      Service (NHS). An independent evaluation of the first 12 months of operation of
      the Australian Capital Territory (ACT) Health walk-in centre, in 2011, analysed
      the translation of evidence from the national evaluation of the NHS walk-in
      centres to the policy development and implementation of the ACT walk-in centre.
      Whilst in a number of ways the evidence was used well, our interest for this
      paper was to examine three areas identified as problematic and to identify the
      points at which the evidence was lost or diluted. METHODS: In addition to data
      obtained through nurse and key stakeholder interviews for the evaluation, an
      analysis was undertaken of documents on the planning and establishment of the ACT
      walk-in centre, either provided to the evaluation team or made publicly
      available. RESULTS: Three areas were identified as problematic in the way that
      evidence from the NHS evaluation was translated: the use of clinical decision
      support software (CDSS); the marketing of the walk-in centre; and its location.
      CONCLUSIONS: Our examination indicates that despite seeking evidence to inform
      the development of the ACT walk-in centre, the evidence was not fully used and
      some clear lessons ignored, resulting in much of the evidence being lost in
      translation.

PMID- 23864422
TI  - Myth: reframing mental illness as a 'brain disease' reduces stigma.

PMID- 23864423
TI  - Osteoarthritis and falls in the older person.
AB  - Osteoarthritis and falls are common conditions affecting older individuals which
      are associated with disability and escalating health expenditure. It has been
      widely assumed that osteoarthritis is an established risk factor for falls in
      older people. The relationship between osteoarthritis and falls has, quite
      surprisingly, not been adequately elucidated, and published reports have been
      conflicting. Our review of the existing literature has found limited evidence
      supporting the current assumption that the presence of osteoarthritis is
      associated with increased risk of falls with suggestions that osteoarthritis may
      actually be protective against falls related fractures. In addition, joint
      arthroplasty appears to increase the risk of falls in individuals with
      osteoarthritis. 

PMID- 23864424
TI  - Health status of UK care home residents: a cohort study.
AB  - BACKGROUND: UK care home residents are often poorly served by existing healthcare
      arrangements. Published descriptions of residents' health status have been
      limited by lack of detail and use of data derived from surveys drawn from social,
      rather than health, care records. AIM: to describe in detail the health status
      and healthcare resource use of UK care home residents DESIGN AND SETTING: a 180
      day longitudinal cohort study of 227 residents across 11 UK care homes, 5 nursing
      and 6 residential, selected to be representative for nursing/residential status
      and dementia registration. METHOD: Barthel index (BI), Mini-mental state
      examination (MMSE), Neuropsychiatric index (NPI), Mini-nutritional index (MNA),
      EuroQoL-5D (EQ-5D), 12-item General Health Questionnaire (GHQ-12), diagnoses and
      medications were recorded at baseline and BI, NPI, GHQ-12 and EQ-5D at follow-up
      after 180 days. National Health Service (NHS) resource use data were collected
      from databases of local healthcare providers. RESULTS: out of a total of 323, 227
      residents were recruited. The median BI was 9 (IQR: 2.5-15.5), MMSE 13 (4-22) and
      number of medications 8 (5.5-10.5). The mean number of diagnoses per resident was
      6.2 (SD: 4). Thirty per cent were malnourished, 66% had evidence of behavioural
      disturbance. Residents had contact with the NHS on average once per month.
      CONCLUSION: residents from both residential and nursing settings are dependent,
      cognitively impaired, have mild frequent behavioural symptoms, multimorbidity,
      polypharmacy and frequently use NHS resources. Effective care for such a cohort
      requires broad expertise from multiple disciplines delivered in a co-ordinated
      and managed way.

PMID- 23864426
TI  - Investigation into the feasibility of thioditaloside as a novel scaffold for
      galectin-3-specific inhibitors.
AB  - Galectin-3 is extensively involved in metabolic and disease processes, such as
      cancer metastasis, thus giving impetus for the design of specific inhibitors
      targeting this beta-galactose-binding protein. Thiodigalactoside (TDG) presents a
      scaffold for construction of galectin inhibitors, and its inhibition of galectin
      1 has already demonstrated beneficial effects as an adjuvant with vaccine
      immunotherapy, thereby improving the survival outcome of tumour-challenged mice.
      A novel approach--replacing galactose with its C2 epimer, talose--offers an
      alternative framework, as extensions at C2 permit exploitation of a galectin-3
      specific binding groove, thereby facilitating the design of selective inhibitors.
      We report the synthesis of thioditaloside (TDT) and crystal structures of the
      galectin-3 carbohydrate recognition domain in complexes with TDT and TDG. The
      different abilities of galactose and talose to anchor to the protein correlate
      with molecular dynamics studies, likely explaining the relative disaccharide
      binding affinities. The feasibility of a TDT scaffold to enable access to a
      particular galectin-3 binding groove and the need for modifications to optimise
      such a scaffold for use in the design of potent and selective inhibitors are
      assessed.

PMID- 23864427
TI  - Recognition of elder abuse by Italian nurses and nursing students: evaluation by
      the Caregiving Scenario Questionnaire.
AB  - Elder abuse appears to be widely underestimated by health professionals. We aimed
      to evaluate the recognition of elder abuse among Italian nurses and nursing
      students related to their professional, personal experiences and socio
      demographic characteristics. 193 nursing students and 76 nurses attending a post
      graduate nursing management master's degree at the University of Bologna (Italy)
      completed the Caregiving Scenario Questionnaire measuring the ability to
      recognize elder abuse. Data on age, gender, previous professional and personal
      experiences as well as nursing school teaching were collected. Regarding abusive
      items, preventing elder's movements by putting a table over the elder's lap was
      identified by almost all participants, while locking someone at home was
      identified by half of them. Neglect was recognized by 25 % of nurses and 20 % of
      students, respectively. The majority of nurses and students correctly identified
      non-abusive strategies. Reporting being taught on elder abuse was inversely
      associated with a good performance in detecting neglect. Italian nurses' and
      nursing students' uncertainty in identifying abusive strategies, especially
      neglect, was consistent with results of previous studies in other countries.
      Standardized education in healthcare core curriculum, reference guidance and
      training are strongly needed to improve elder abuse recognition in Italy. 

PMID- 23864428
TI  - Unhealthy and healthy food consumption inside and outside of the school by pre
      school and elementary school Mexican children in Tijuana, Mexico.
AB  - Food from lunch packs (LP) or food available inside and outside of school can
      play an important role in the development of obesity. The purpose of this study
      was to evaluate the LP of elementary school (ES) and preschool children (PS) in
      Tijuana, and the foods available to them inside and outside of school. Eight
      public schools participated in the study. A random sample of all the groups from
      a school district was conducted. A questionnaire was administered to children in
      first through sixth grade (ES) and to the parents of PS. LP and food available
      inside and outside of the school were classified as healthy, unhealthy, and
      adequate according to the guidelines set forth by the Secretariat of Health. A
      total of 2,716 questionnaires were administered and the content of 648 LP was
      assessed. It was observed that 99% of PS had LP prepared at home, a higher
      percentage than ES. None of the LP of the ES was classified as healthy, and 1%
      was classified as adequate. Among PS, 21% of the LP were classified as healthy
      and 6% as adequate. More than half of the children recognized the brand name of
      foods high in fat, salt, and added sugar available inside and outside of school
      grounds. Most of the LP of ES and PS and the foods available inside and outside
      of school were unhealthy and inadequate. A strategy to prevent the availability
      of unhealthy and inadequate food in LP and foods available inside and outside
      schools is recommended.

PMID- 23864429
TI  - Health conditions of recyclable waste pickers.
AB  - The presence of chronic non-communicable diseases (NCDs) among vulnerable
      populations is a rarely discussed subject. Thus, the present cross-sectional
      descriptive study aimed to analyse the health conditions and access to public
      health services of 268 waste pickers in southern Brazil. Regarding NCDs, their
      prevalence of hypertension was 32.8 %, diabetes 11.4 %, dyslipidemia 16.4 %,
      overweight 51.1 %, obesity 25.7 % and abdominal obesity 57.8 %. Regarding access
      to health services, 36.9 % of the sample had not consulted with a doctor in more
      than 1 year, 15.7 % had no access to a healthcare unit, 7.5 % had never measured
      their blood pressure, 45.9 % had never had a glucose test, and 61.2 % had never
      had a triglyceride test. The statistical analysis showed that whereas men had
      gone longer since their last medical consultation and blood pressure measurement,
      women had increased frequencies of overweight, abdominal obesity, awareness of
      their hypertension and use of anti-hypertensive drugs (p < 0.05). Therefore, the
      health profile of waste pickers is critical, with a high prevalence of NCDs and
      poor healthcare usage. Strategies to improve monitoring and treatment are
      recommended. 

PMID- 23864430
TI  - Functional binding analysis of human fibrinogen as an iron- and heme-binding
      protein.
AB  - Human fibrinogen is a metal ion-binding protein, but its mechanism of binding
      with iron and heme has not been elucidated in detail. In this study, human
      fibrinogen was immobilized on CNBr-activated Sepharose 4B beads. The fibrinogen
      beads bound hemin (iron-protoporphyrin IX: PPIX) as well as iron ion released
      from ferrous ammonium sulfate (FAS) more efficiently than Sepharose 4B beads
      alone. Hemin bound to fibrinogen still exhibited pseudo-peroxidase activity. The
      affinity of fibrinogen binding to hemin, Sn-PPIX, Zn-PPIX and metal-free PPIX
      followed the order Sn-PPIX metal-free PPIX < hemin < Zn-PPIX; PPIX bound more non
      specifically to control beads. FAS significantly enhanced the binding of hemin to
      fibrinogen beads. These results suggest that human fibrinogen directly recognizes
      iron ion, the PPIX ring and metal ions complexed with the PPIX ring, and that the
      binding of hemin is augmented by iron ions.

PMID- 23864431
TI  - Characterization of two genes encoding metal tolerance proteins from Beta
      vulgaris subspecies maritima that confers manganese tolerance in yeast.
AB  - Manganese (Mn(2+)) is an essential micronutrient in plants. However increased
      Mn(2+) levels are toxic to plant cells. Metal tolerance proteins (MTPs), member
      of cation diffusion facilitator protein (CDF) family, have important roles in
      metal homeostatis in different plant species and catalyse efflux of excess metal
      ions. In this study, we identified and characterized two MTP genes from Beta
      vulgaris spp. maritima (B. v. ssp. maritima). Overexpression of these two genes
      provided Mn tolerance in yeast cells. Sequence analyses displayed BmMTP10 and
      BmMTP11 as members of the Mn-CDF family. Functional analyses of these proteins
      indicated that they are specific to Mn(2+) with a role in reducing excess
      cellular Mn(2+) levels when expressed in yeast. GFP-fusion constructs of both
      proteins localized to the Golgi apparatus as a punctuated pattern. Finally, Q-RT
      PCR results showed that BmMTP10 expression was induced threefold in response to
      the excess Mn(2+) treatment. On the other hand BmMTP11 expression was not
      affected in response to excess Mn(2+) levels. Thus, our results suggest that the
      BmMTP10 and BmMTP11 proteins from B. v. ssp. maritima have non-redundant
      functions in terms of Mn(2+) detoxification with a similar in planta localization
      and function as the Arabidopsis Mn-CDF homolog AtMTP11 and this conservation
      shows the evolutionary importance of these vesicular proteins in heavy metal
      homeostatis among plant species.

PMID- 23864432
TI  - Synthesis of novel peptides through Ugi-ligation and their anti-cancer
      activities.
AB  - Proline-rich heptapeptide was synthesized and its structure was modified through
      Ugi-ligation. The desired pseudopeptides were separated as diastereomers and
      their anti-cancer activities were investigated. Their in vitro anti-cancer
      activities were investigated by treating HL60 (leukemia cancer cells), MCF7
      (breast cancer cells) and A549 (lung cancer cells) cells with appropriate amounts
      of synthesized peptides. Our in vitro studies suggest that compounds 11a-b, 11i
      j, and 11e had little or no effect on cancer cells viabilities. 

PMID- 23864433
TI  - Transport of asymmetric dimethylarginine (ADMA) by cationic amino acid
      transporter 2 (CAT2), organic cation transporter 2 (OCT2) and multidrug and toxin
      extrusion protein 1 (MATE1).
AB  - Asymmetric dimethylarginine (ADMA), inhibiting the nitric oxide (NO) synthesis
      from L-arginine, is a known cardiovascular risk factor. Our aim was to
      investigate if ADMA and/or L-arginine are substrates of the human cationic amino
      acid transporters 2A (CAT2A, SLC7A2A) and 2B (CAT2B, SLC7A2B), the organic cation
      transporter 2 (OCT2, SLC22A2), and the multidrug and toxin extrusion protein 1
      (MATE1, SLC47A1). We systematically investigated the kinetics of ADMA and L
      arginine transport in human embryonic kidney (HEK293) cells stably overexpressing
      CAT2A, CAT2B, OCT2, or MATE1. Vector-only transfected HEK293 cells served as
      controls. Compared to vector control cells, uptake of ADMA and L-arginine was
      significantly higher (p < 0.05) in cells expressing CAT2B and OCT2 at almost all
      investigated concentrations, while cells expressing CAT2A only showed a
      significant uptake at concentrations above 300 MUM. Uptake of MATE1
      overexpressing cells was significantly (p < 0.05) higher at pH 7.8 and 8.2 than
      controls. Apparent V max values (nmol mg protein(-1) min(-1)) for cellular uptake
      of ADMA and L-arginine were ~11.8 +/- 1.2 and 19.5 +/- 0.7 for CAT2A, ~14.3 +/-
      1.0 and 15.3 +/- 0.4 for CAT2B, and 6.3 +/- 0.3 and >50 for OCT2, respectively.
      Apparent K m values (MUmol/l) for cellular uptake of ADMA and L-arginine were
      ~3,033 +/- 675 and 3,510 +/- 419 for CAT2A, ~4,021 +/- 532 and 952 +/- 92 for
      CAT2B, and 967 +/- 143 and >10,000 for OCT2, respectively. ADMA and L-arginine
      are substrates of human CAT2A, CAT2B, OCT2 and MATE1. Transport kinetics of
      CAT2A, CAT2B, and OCT2 indicate a low affinity, high capacity transport, which
      may be relevant for renal and hepatic elimination of ADMA or L-arginine. 

PMID- 23864434
TI  - The role of L-arginine-nitric oxide pathway in bacterial translocation.
AB  - This study investigated the nitric oxide (NO) role as a mediator of arginine on
      bacterial translocation (BT) and gut damage in mice after intestinal obstruction
      (IO). The effects of pretreatment with arginine with or without NO inhibition on
      the systemic and local immunological response were also assessed. Mice were
      categorized into four groups. Group ARG received chow containing 2 % arginine,
      while group ARG + L-NAME received the same diet plus L-NAME (N-nitro-L-arginine
      methyl ester) by gavage. The IO and Sham groups were fed standard chow. After 7
      days, animals were gavaged with radiolabeled Escherichia coli, anesthetized and
      subjected to IO, except the Sham group. Animals were euthanized after 18 h, and
      BT was evaluated in the mesenteric lymph nodes, blood, liver, spleen and lungs.
      In another experiment, the intestinal injury was assessed regarding intestinal
      permeability and ileum histological analyses. Intestinal secretory immunoglobulin
      A (sIgA) levels, serum IFN-gamma and IL-10 cytokines were assessed. Arginine
      reduced BT, but NO inhibition enhanced BT compared with the ARG group (p < 0.05).
      Intestinal permeability in the ARG and ARG + L-NAME groups was similar but
      decreased when compared with the IO group (p < 0.05). Histological preservation
      was observed. Arginine treatment increased IL-10 and sIgA levels when compared
      with the Sham and IO groups (p < 0.05). The cytokines and sIgA concentrations
      were similar in the ARG + L-NAME and Sham groups. Arginine appeared to reduce BT
      and its effects on the modulation of cytokines and secretory IgA in mice after IO
      are mediated by NO production.

PMID- 23864435
TI  - Extrapolation of survival data in cost-effectiveness analyses: improving the
      current state of play.

PMID- 23864436
TI  - Identification of marker proteins by orthodontic treatment: relationship of RANKL
      in the gingival crevicular fluid and of amylase in whole saliva with orthodontic
      treatment.
AB  - Orthodontic medical treatment is performed to move a tooth to the optimal
      position to obtain optimal occlusion. Orthodontic treatment is accompanied by
      mechanical stress due to orthodontic force and by psychological stress that is
      experienced as pain or displeasure. The purpose of this study was to identify
      stress marker proteins during orthodontic treatment. Levels of receptor activator
      of NFkappaB (RANKL) and heat shock protein 70 (HSP70) in the gingival crevicular
      fluid (GCF) were analyzed as markers of mechanical stress, and levels of
      chromogranin A (CgA) and amylase in whole saliva were analyzed as markers of
      psychological stress. GCF was collected from control and experimental teeth at
      initiation of treatment and 24 h after treatment. Whole saliva was collected
      before treatment, at initiation of treatment and 24 h after treatment. RANKL was
      expressed at 24 h after treatment in the experimental GCF, but not in the control
      GCF. HSP70 appeared to be constitutively expressed in GCF, and its levels showed
      no major change between the control and experimental groups from initiation of
      treatment to 24 h after treatment. Amylase activity in whole saliva was enhanced
      at 24 h after treatment compared to control, but CgA levels showed little change
      between the groups. These results indicated that RANKL and amylase may be the
      candidate markers for mechanical and psychological stress, respectively, during
      orthodontic treatment, even though the total protein concentration and amylase
      activity displayed a large standard deviation among subjects. Further studies are
      therefore required to establish these markers for clinical use.

PMID- 23864437
TI  - Reduction in choroidal thickness of macular area in polypoidal choroidal
      vasculopathy patients after intravitreal ranibizumab therapy.
AB  - BACKGROUND: To evaluate changes in retinal and choroidal thickness changes after
      three intravitreal ranibizumab (IVR) injections for polypoidal choroidal
      vasculopathy (PCV) using enhanced depth-imaging-optical coherence tomography (EDI
      OCT). METHODS: In this retrospective, observational case series, EDI-OCT was used
      to measure changes in choroidal thickness at nine points in a lattice shape in
      the macula before and after introductory-stage IVR. RESULTS: Choroidal thickness
      was decreased at all nine points in the lattice shape, but was significantly
      decreased only at the fovea. CONCLUSION: The subfoveal choroidal thickness may be
      reduced by introductory-stage IVR in patients with PCV. In particular, choroidal
      thickness at the fovea was reduced during the early stage of treatment.

PMID- 23864438
TI  - Attention-deficit/hyperactivity disorder and alexithymia: a pilot study.
AB  - Although the relationship between alexithymia and psychopathology has been
      studied extensively in adults, research is lacking on alexithymia in childhood
      psychopathology. The aim of this study was to investigate the relationship
      between alexithymia and attention-deficit/hyperactivity disorder (ADHD). The
      Italian version of the Alexithymia Questionnaire for Children was administered to
      a sample of 50 children with a DSM-IV diagnosis of ADHD, as assessed by means of
      the K-SADS PL, and to 100 healthy, age- and sex-matched children without ADHD.
      The total alexithymia score as well as the difficulty in identifying feelings
      (DIF) and externally oriented thinking factors were significantly associated with
      ADHD. The total alexithymia score, the DIF, and the difficulty in describing
      feelings factors were also significantly associated with symptoms of
      hyperactivity/impulsivity. No significant relationship between alexithymia and
      inattentiveness symptoms emerged. Results provide preliminary data on the
      relationship between alexithymia and ADHD. Findings point to an association
      between difficulty in identifying emotions and hyperactivity/impulsivity. Future
      studies conducted on larger patient samples, as well as longitudinal designs, are
      warranted to confirm our findings.

PMID- 23864439
TI  - Epigenetics primer: why the clinician should care about epigenetics.
AB  - Epigenetics describes heritable alterations of gene expression that do not
      involve DNA sequence variation and are changeable throughout an organism's
      lifetime. Not only can epigenetic status influence drug response, but it can also
      be modulated by drugs. In this review, the three major epigenetic mechanisms are
      described: covalent DNA modification, histone protein modification, and
      regulation by noncoding RNA. Further, this review describes how drug therapy can
      influence, and be influenced by, these mechanisms. Drugs with epigenetic
      mechanisms are already in use, with many more likely to be approved within the
      next few years. As the understanding of epigenetic processes improves, so will
      the ability to use these data in the clinic to improve patient care. 

PMID- 23864440
TI  - Enhancement of vindoline and vinblastine production in suspension-cultured cells
      of Catharanthus roseus by artemisinic acid elicitation.
AB  - Elicitation is an important strategy to improve production of secondary
      metabolites in vitro. Artemisinic acid was studied as a novel elicitor to enhance
      the yield of terpenoid indole alkaloids in the present paper. Our results
      demonstrated that the concentrations of vindoline and vinblastine were increased
      by sixfold and twofold, respectively, compared to those of the control group
      after treatment with artemisinic acid. To elucidate the underlying mechanism, we
      investigated the gene expression of four enzymes involved in the biosynthetic
      pathway of vinblastine in the suspension-cultured cells of Catharanthu sroseus.
      RT-PCR experiment showed that artemisinic acid was able to up-regulate the
      transcriptions of tryptophan decarboxylase, geraniol 10-hydroxylase, tabersonine
      16-hydroxylase and deacetoxyvindoline 4-hydroxylase. 

PMID- 23864441
TI  - Structural and functional diversity of rhizobacteria associated with Rauwolfia
      spp. across the Western Ghat regions of Karnataka, India.
AB  - The present study carried out with denaturing gradient gel electrophoresis of DNA
      extracted from rhizosphere soils of Rauwolfia spp. collected from Western Ghat
      (WG) regions of Karnataka indicated that Pseudomonas sp. was prevalently found
      followed by Methylobacterium sp., Bacillus sp. and uncultured bacteria. A total
      of 200 rhizobacteria were isolated from 58 rhizosphere soil samples comprising of
      15 different bacterial genera. The Shannon Weaver diversity index (H') and
      Simpson's diversity index (D) were found to be 2.57 and 0.91 for cultivable
      bacteria, respectively. The total species richness of cultivable rhizobacteria
      was high in Coorg district comprising 15 bacterial genera while in Mysore
      district, four bacterial genera were recorded. Rarefaction curve analysis also
      indicated the presence of higher species richness in samples of Shimoga and
      Coorg. All the rhizobacteria were screened for their multiple plant growth
      promotion and disease suppression traits. The results revealed that 70% of the
      isolates colonized tomato roots, 42% produced indole acetic acid, 55% solubilized
      phosphorus, while 43, 22, 27, 19, 40, 15 and 44% produced siderophore, salicylic
      acid, hydrogen cyanide, chitinase, phytase, cellulase and protease, respectively.
      Rhizobacterial isolates showing antagonistic activity against Fusarium oxysporum
      and Aspergillus flavus were 53 and 33%, respectively. Plant growth promotion
      studies revealed that most of the isolates increased percent germination with
      significantly higher vigour index as compared to untreated control. Most
      predominant rhizobacteria found in the rhizospheres of Rauwolfia spp. of WG
      regions are potential PGPR which can serve as biofertilizers and biopesticides.

PMID- 23864443
TI  - First-day weight loss predicts eventual weight nadir for breastfeeding newborns.
AB  - OBJECTIVE: To examine the relationship between high (>=5%) weight loss during the
      first 24 h after birth and eventual excess weight loss (EWL) of >=10% of birth
      weight. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Northern
      California hospitals. PATIENTS: 63 096 infants born at >=36 weeks in 2009-2010,
      of whom 59 761 (94.5%) had a weight subsequent to birth weight measured at <24 h.
      MAIN PREDICTOR MEASURE: Per cent of birth weight lost by 24 h of age. MAIN
      OUTCOME MEASURE: Weight nadir, defined as the lowest recorded inpatient or
      outpatient weight in the first 30 days after birth, expressed as a percentage of
      birth weight. RESULTS: Among infants who breastfed at least once, mean (+/-SD)
      weight nadir was 6.3+/-3.5% below birth weight, and 9.6% of the newborns lost
      >=10% of birth weight. Among 2670 infants who lost >=5% of their birth weight in
      the first 24 h, 782 (29%) eventually developed EWL, compared with 4840 (8%) of 57
      109 infants who lost <5% (p<0.0005). In multivariate analysis, >=5% first-day
      weight loss predicted eventual EWL (>=10%) with an OR of 4.06 (95% CI 3.69 to
      4.46) after adjusting for gestational age, method of delivery, maternal
      race/ethnicity and hospital of birth. CONCLUSIONS: High first-day weight loss
      predicts eventual weight nadir and can be used to identify infants who might
      benefit from targeted interventions to support breastfeeding and prevent EWL.

PMID- 23864444
TI  - The joint use of the tangential electric field and surface Laplacian in EEG
      classification.
AB  - We investigate the joint use of the tangential electric field (EF) and the
      surface Laplacian (SL) derivation as a method to improve the classification of
      EEG signals. We considered five classification tasks to test the validity of such
      approach. In all five tasks, the joint use of the components of the EF and the SL
      outperformed the scalar potential. The smallest effect occurred in the
      classification of a mental task, wherein the average classification rate was
      improved by 0.5 standard deviations. The largest effect was obtained in the
      classification of visual stimuli and corresponded to an improvement of 2.1
      standard deviations. 

PMID- 23864442
TI  - Do very preterm twins and singletons differ in their neurodevelopment at 5 years
      of age?
AB  - OBJECTIVE: Twins have inconsistently shown poorer outcomes than singletons.
      Although a high proportion of twins are born very preterm, data are sparse on the
      long-term outcomes in very preterm twins. The objective of this study was to
      compare mortality and neurodevelopmental outcomes of very preterm singletons and
      twins and to study outcomes in relation to factors specific to twins. DESIGN:
      Birth cohort study Etude Epidemiologique sur les Petits Ages Gestationnels
      (EPIPAGE). SETTING: Nine regions in France. PATIENTS: All very preterm live
      births occurring from 22 to 32 weeks of gestation in all maternity wards of nine
      French regions in 1997 (n=2773). MAIN OUTCOMES MEASURES: Neurodevelopmental
      status, including cerebral palsy, and a cognitive assessment with the Kaufman
      Assessment Battery for Children, with scores on the Mental Processing Composite
      (MPC) scale, was available for 1732 and 1473 children at 5 years of age,
      respectively. RESULTS: Among live births, twins had higher hospital mortality
      than singletons (adjusted (a)OR: 1.4 (95% CI 1.1 to 1.9)). Among survivors, there
      was no crude difference at 5 years between twins and singletons in the prevalence
      of cerebral palsy (8.0% vs 9.1%, respectively), MPC <70 (9.5% vs 11.1%) and mean
      MPC (94.6 vs 94.4). However, after adjustment for sex, gestational age,
      intrauterine growth restriction and social factors, twins were more likely to
      have lower MPC scores (mean difference: -2.4 (95% CI-4.8 to 0.01)). Live born
      twins had a higher risk of mortality when birth weight discordance was present
      (aOR:2.9 (95% CI 1.7 to 4.8)), but there were no differences in long-term
      outcomes. CONCLUSIONS: Compared with very preterm singletons, twins had higher
      mortality, no difference with respect to severe deficiencies, but slightly lower
      MPC scores at 5 years.

PMID- 23864445
TI  - Both HCV and HBV are major causes of liver cancer in Southeast Asians.
AB  - The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than
      in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus
      (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology
      of liver disease associated with HCC in subgroups of Asian Americans. This was an
      analysis of 510 Asian HCC patients at a US medical center. Patients were
      identified using ICD9 diagnosis. Multivariate logistic regression was used to
      study predictors of HCV as the cause of HCC. Patients were Southeast Asian,
      Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast
      Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and
      Korean patients had a higher proportion of HBV-related HCC. HCC was usually
      associated with HBV in Chinese and Korean patients, but both HCV and HBV were
      important associations in Southeast Asians. 

PMID- 23864446
TI  - Impaired hepatocyte maturation, abnormal expression of biliary transcription
      factors and liver fibrosis in C/EBPalpha(Cebpa)-knockout mice.
AB  - Inactivation of the C/EBPalpha gene (Cebpa) in the mouse not only causes impaired
      hepatocyte maturation, but also induces pseudoglandular structures in the liver
      parenchyma. The present study was undertaken to determine how the expression of
      other transcription factors controlling differentiation into hepatocytes and
      biliary epithelial cells is affected, and how the hepatic architecture, including
      the bile and vascular systems, is disordered in the fetal knockout liver.
      Histochemical analyses demonstrated that the expression of HNF1alpha and
      HNF4alpha was heterogeneous in the knockout liver, and that not all parenchymal
      cells (pseudoglandular) expressed these transcription factors, whereas
      parenchymal cells in the wild-type liver homogeneously expressed these
      transcription factors. SOX9, which was expressed only in biliary cells in the
      wild-type liver, was detectable in many pseudoglandular cells of the knockout
      liver. Although the pseudoglandular cells often coexpressed SOX9 and
      HNF1alpha/HNF4alpha, cells expressing SOX9 but not expressing HNF1alpha/HNF4alpha
      (biliary cells) were sometimes detectable in the parenchyma. Periportal biliary
      structures were abnormal in their segregation from the parenchyma and in their
      expression of the transcription factors and Ep-CAM, a biliary adhesion molecule.
      These results suggest that the inactivation of the Cebpa gene causes unstable
      expression of liver-enriched transcription factors or biliary transcription
      factors and elevated expression of Ep-CAM, which may lead to abnormal biliary
      morphogenesis in the knockout liver. The impaired maturation of the parenchyma
      caused elevated expression of PECAM-1, desmin and Foxf1, suggesting that the
      maturation of the parenchyma plays an important role in the normal histogenesis
      of nonparenchymal cells (stellate cells and sinusoidal endothelial cells).

PMID- 23864447
TI  - Endosonography-assisted transmural endoscopic drainage of pancreatic pseudocysts:
      a single center experience.
AB  - BACKGROUND/AIMS: Management of pancreatic pseudocysts can be challenging.
      Endosonography-guided drainage of the pseudocysts is an important treatment
      modality. In this study, we evaluated the results of endosonography-guided
      transmural endoscopic drainage of these lesions. MATERIALS AND METHODS: We
      performed drainage of the pancreatic pseudocysts through the stomach or duodenum
      using a linear endosonography device. The procedure steps were as follows:
      Determination of the best location for needle insertion, puncture of the cyst,
      guide insertion, creation of a window between the cyst and stomach lumen using a
      cystotome, and finally insertion of a double pigtail catheter. RESULTS: The
      procedure was applied to 12 patients (8 males, 4 females, mean age: 51 +/- 15.6
      years), with success achieved in 10 patients (83%), defined as complete
      disappearance of the cyst. The mean cyst diameter was 9 cm (range: 6-12 cm).
      There was only one complication (8%), as an intraabdominal abscess with an
      uncomplicated course after surgical drainage. CONCLUSIONS: Endosonography-guided
      drainage is an effective and safe method for the management of pancreatic
      pseudocysts.

PMID- 23864448
TI  - Typical symptoms rather than extraesophageal symptoms affect the quality of life
      in gastroesophageal reflux disease.
AB  - BACKGROUND/AIMS: Compared with the general population, the quality of life of
      patients with gastroesophageal reflux disease has been known to be impaired. The
      aim of this study was to assess and compare how typical esophageal symptoms and
      extraesophageal symptoms affect quality of life. MATERIALS AND METHODS: This
      study was performed in patients who had visited the Health Promotion Center of
      St. Paul's Hospital and undergone an endoscopy. Two instruments were used to
      assess quality of life: a questionnaire on the symptoms of gastroesophageal
      reflux disease and the Korean version of the World Health Organization Quality of
      Life Scale, Abbreviated Version. For comparison purposes, data from an age
      matched healthy control group were obtained. RESULTS: In this study, 262 health
      check-up subjects were classified with gastroesophageal reflux disease. An
      additional 447 health check-up subjects, who had shown normal and asymptomatic
      results from endoscopy, were assigned to the control group. The quality of life
      in gastroesophageal reflux disease patients was lower than that of the control
      group (81.7 vs. 87.5, p < 0.05). Compared to the group with asymptomatic erosive
      reflux disease and the control group, the quality of life was also lower in the
      group that manifestedboth typical symptoms and extraesophageal symptoms (79.9 vs.
      84.5, p < 0.05). Compared with the control group, the quality of life was lower
      in the group with typical symptoms than in the group with extraesophageal
      symptoms (79.6 vs. 87.5, p < 0.05). CONCLUSIONS: Regardless of whether the
      esophagitis was erosive or non-erosive, the quality of life was deteriorated to a
      greater extent in symptomatic gastroesophageal reflux disease patients than in
      the control group, and the quality of life was even lower among patientswho had
      typical symptoms than among patients with extraesophageal manifestations.

PMID- 23864449
TI  - The diagnostic accuracy of urine IgG antibody tests for the detection of
      Helicobacter pylori infection in Turkish dyspeptic patients.
AB  - BACKGROUND/AIMS: There is increasing interest in noninvasive tests for the
      assessment of Helicobacter pylori infection, and urine-based tests have been
      widely used as noninvasive tests to detect Helicobacter pylori infection. The aim
      of this study was to evaluate the adaptation and usefulness of urine antibody
      enzyme-linked immunosorbent assay and urine card tests in the clinical setting to
      detect anti-Helicobacter pylori IgG antibody excreted into urine in Turkish adult
      patients with dyspepsia. MATERIALS AND METHODS: One-hundred twenty-four patients
      who were admitted and referred for upper endoscopy to Dokuz Eylul University
      Hospital, Gastroenterology Clinic were studied. Antrum and corpus biopsies were
      taken, and Helicobacter pylori status was defined in the presence of at least two
      positive results of rapid urease test, histopathology and culture. Urine and
      serum specimens of 124 patients were collected and examined for anti-Helicobacter
      pylori IgG antibody by URINELISA, RAPIRUN (Otsuka Pharmaceutical, Tokyo, Japan)
      and anti-Helicobacter pylori enzyme-linked immunosorbent assay (Euroimmun,
      Lubeck, Germany) tests, respectively. RESULTS: Helicobacter pylori infection was
      positive in 82 (66.1%) patients according to the gold standard methods. Among 82
      Helicobacter pylori infection-positive patients, 69 patients were positive by
      both URINELISA and RAPIRUN; 109 of 124 patients were positive by anti
      Helicobacter pylori IgG enzyme-linked immunosorbent assay. The sensitivity and
      specificity of URINELISA, RAPIRUN and anti-Helicobacter pylori IgG enzyme-linked
      immunosorbent assay were 74.4%, 73.2%, 100% and 81.0%, 78.6%, 35.7%,
      respectively. However, the urine antibody test cut-off values were searched for
      the best concordance with the results of gold standard methods. This yielded that
      the sensitivity and specificity of URINELISA with our new cut-off value (0.530)
      were 90.2% and 71.4%, respectively. CONCLUSIONS: As a first study among Turkish
      adult patients with dyspepsia, the efficacy of URINELISA was related with the
      determination of a new cut-off value for pretreatment as a screening test value.
      We suggest that the cut-off value of the URINELISA test should be evaluated and
      considered for each patient group and each country. The URINELISA (OD 0.530) and
      RAPIRUN tests were found useful for the diagnosis of Helicobacter pylori
      infection in our patients with dyspepsia.

PMID- 23864450
TI  - The relation between serum cytokeratin 18 and acute pancreatitis: can it be a
      serological predictive marker?
AB  - BACKGROUND/AIMS: Acute pancreatitis is well defined as pancreatic inflammation
      due to the activation of pancreatic enzymes secondary to several etiological
      factors. In the majority of patients, the clinical symptoms are self-limited, but
      it can also cause tissue necrosis and severe organ failures. In experimental
      animal models, it has been shown that wide apoptotic cell death is related to a
      clinically mild presentation of acute pancreatitis. Cytokeratin 18, a
      cytoskeletal protein, is shown to be related with apoptosis. In this study, we
      aimed to show the relation between serum cytokeratin 18 and the clinical
      presentation of acute pancreatitis in humans. MATERIALS AND METHODS: A total of
      54 acute pancreatitis patients were enrolled into the study. Patients were
      classified as mild or severe pancreatitis according to Ranson's criteria. There
      were 36 (66.7%) patients in the mild pancreatitis group (score < 6), and 18
      (33.3%) patients in the severe pancreatitis group (score >= 6). During the first
      admission, blood samples were obtained for serum cytokeratin 18 levels. RESULTS:
      Cytokeratin 18 levels in the mild pancreatitis group were significantly higher
      than in the severe pancreatitis group (271.2 +/- 45.5 vs. 152.6 +/- 38.2 IU/L; p
      < 0.001). There was a negative correlation between the disease activity score
      (Ranson score) and the serum cytokeratin 18 levels (p < 0.001; r = -0.724).
      CONCLUSIONS: This first human study suggests that cytokeratin 18 (marker of
      apoptosis) might be a serological predictive marker for acute pancreatitis for
      disease activity.

PMID- 23864451
TI  - Gallbladder metastasis secondary to gastric cancer as a first site of recurrence
      presented with acute cholecystitis: case report and literature review.
AB  - Metastasis to the gallbladder from other malignancies is extremely rare and is
      related with a very poor prognosis. Malignant melanoma has been reported to be
      the most common origin of gallbladder metastasis. Although only eight cases of
      gallbladder metastasis originating from gastric cancer have been documented in
      the literature based on small series, of these cases, only one case with signet
      ring cell carcinoma histology has been reported previously. We report the case of
      a 58-year-old male with early-stage signet ring cell carcinoma of the stomach who
      presented with acute cholecystitis previously treated with curative gastrectomy.
      After laparoscopic cholecystectomy, the diagnosis of gallbladder metastasis with
      signet ring cell histology secondary to gastric cancer was made. To our
      knowledge, this is only the second case of signet ring cell carcinoma of the
      stomach metastasized to the gallbladder as a first site of recurrence. We suggest
      that for patients with gastric cancer who complain of the findings of acute
      cholecystitis or cholecystolithiasis, gallbladder metastasis from gastric cancer
      should be considered in the differential diagnosis. 

PMID- 23864452
TI  - A case of endoscopic ultrasound diagnosis of gastric amyloidosis.
AB  - A 37-year-old female presented to our hospital with the complaint of abdominal
      distension for one month. A gastroscopy examination showed extensive chyme
      retention and varying erosion and ulceration of the gastric body. The pathology
      showed moderate chronic inflammation and erosion of the gastric body mucosa, with
      accompanying Helicobacter pylori infection. She accepted treatment for one month.
      The patient then accepted to undergo endoscopic ultrasonography, which showed
      that normal structure of the gastric body intumescence was discernible. The
      pathology showed chronic mild-moderate inflammation of the gastric body mucosa
      associated with interstitial amyloidosis, with accompanying Helicobacter pylori
      infection. She accepted treatment for the eradication of Helicobacter pylori, and
      the original ulcer healed. 

PMID- 23864453
TI  - The advantage of retrieval PEG tubes in patients with buried bumper syndrome - a
      case report.
AB  - The aging population has resulted in an increasing need for long-term enteral
      nutrition of patients with a wide range of disabling conditions. Percutaneous
      endoscopic gastrostomy is one of the applicable methods for long-term enteral
      nutrition support. The buried bumper syndrome is a rarely encountered but grave
      complication of percutaneous endoscopic gastrostomy. Various internal and
      external methods have been described for the removal of the buried bumper.
      Removing the percutaneous endoscopic gastrostomy tube by external traction
      without an abdominal incision can resolve this problem efficiently, especially in
      cases in whom retrieval-type percutaneous endoscopic gastrostomy tubes have been
      used. We report a case of buried bumper syndrome as a late complication of
      percutaneous endoscopic gastrostomy placement. We removed the buried bumper with
      external traction and placed a new percutaneous endoscopic gastrostomy tube in a
      different site because of the peristomal infection. 

PMID- 23864454
TI  - Abdominal cocoon syndrome: preoperative diagnostic criteria, good clinical
      outcome with medical treatment and review of the literature.
AB  - Sclerosing encapsulating peritonitis, or abdominal cocoon syndrome, was described
      firstly in young adolescent girls. It is characterized by a thick fibrotic
      peritoneum that wraps the bowel in a concertina-like fashion with some adhesions.
      We report a man with intermittent intestinal obstruction and an abdominal cocoon
      encasing the small bowel. Our patient had no history of peritonitisor
      tuberculosis. We think he had primary abdominal cocoon syndrome. To the best of
      our knowledge, very few male patients have been reported in the medical
      literature as developing this condition. We treated the patient with drug
      therapy, including steroidand mycophenolate mofetil, and a liquid diet program,
      without surgical operation. He was symptom-free on follow-up over a period of 11
      months. 

PMID- 23864455
TI  - Ganglioneuromatous polyposis of the colon in a patient with multiple adenomatous
      polyps.
AB  - Ganglioneuroma of the gastrointestinal tract is an extremely rare neuroectodermal
      tumor that can be located in the colon. In clinical practice, it is usually
      associated with a systemic disease. Herein, we report a case presented with
      intermittent rectal bleeding and finally diagnosed with ganglioneuromatous
      polyposis and multiple adenomatous polyps in the colon. We also discuss the
      patients reported in the pertinent literature. 

PMID- 23864456
TI  - Hepatic artery pseudoaneurysm as a cause of gastrointestinal system bleeding: a
      case report with a brief review of the literature.
AB  - A hepatic artery pseudoaneurysm is, by definition, a pulsatile hematoma due to a
      leakage of blood through a tear or disruption of the arterial wall, and the blood
      is contained only by the hepatic parenchyma or surrounding hematoma. It can be a
      very rare cause of gastrointestinal system bleeding. These pseudoaneurysms are
      usually very well managed by angiographic intervention. However, in some cases,
      surgery is inevitable. Herein, we present a 63-year-old female presenting with
      gastrointestinal system bleeding 45 days after surgery for cholangiocarcinoma.
      She was found to be bleeding from a pseudoaneurysm of the hepatic artery and
      underwent surgical intervention. 

PMID- 23864457
TI  - Ischemic skin necrosis following terlipressin therapy: report of two cases and
      review of the literature.
AB  - Terlipressin is a synthetic vasopressin analogue that is used in the treatment of
      bleeding esophageal varices and hepatorenal syndrome in patients with cirrhosis.
      Hepatorenal syndrome is a form of renal failure seen in patients with cirrhosis,
      with fatal outcomes. Ischemic adverse effects related to terlipressin are rarely
      observed. Herein, two cases who developed ischemic skin necrosis due to
      terlipressin usage are presented. Terlipressin therapy was started in two
      cirrhotic patients with presumptive hepatorenal syndrome. During the therapy,
      ecchymotic and necrotic changes were observed on the scrotal regions of both
      patients. Skin lesions were relieved after terlipressin therapy. Biopsy results
      were consistent with ischemia. Even if seen rarely, possible emergence of
      ischemic complications must be considered. 

PMID- 23864458
TI  - Unusual cholangiographic findings in a patient with primary sclerosing
      cholangitis: cystic dilatation.
AB  - A 45-year-old woman with the diagnosis of primary sclerosing cholangitis and
      ulcerative colitis admitted with the complaints of pruritus and jaundice.
      Endoscopic retrograde cholangiography revealed entirely narrow, irregular common
      bile duct and common hepatic duct and unusual cystic dilations in the common
      hepatic duct and left hepatic duct. Balloon dilation of the common bile duct was
      performed, and a 10 F double pigtail stent was inserted into the cyst. Three
      months after the endoscopic retrograde cholangiography, cystic dilatations had
      completely resolved. Primary sclerosing cholangitis may present with cystic
      dilatations upto a level that it may resemble Caroli disease. 

PMID- 23864459
TI  - A case of biliary cystadenocarcinoma with malignant seeding of the tract after
      percutaneous catheter drainage.
AB  - Biliary cystadenocarcinoma is rare tumor that originates from the hepatobiliary
      epithelium, and its clinical diagnosis is difficult during the preoperative
      course. A 65-year-old woman with biliary cystadenocarcinoma was misdiagnosed as
      hepatic abscess and underwent ultrasonography-guided percutaneous catheter
      drainage. Ten months later, the patient was re-admitted to our department with a
      mucin-producing cauliflower-like mass measuring 10x10x5 cm3 at the site of
      puncture. Tumor seeding through the percutaneous catheter drainage tract was
      diagnosed. Complete resection of the primary and metastatic tumor with partial
      abdominal wall tissue was performed. No local recurrence could be found after a
      follow-up of more than two years.

PMID- 23864460
TI  - Splenomegaly as the first manifestation of pancreatic adenosquamous carcinoma: a
      case report.
AB  - Adenosquamous carcinoma of the pancreas directly invading surrounding organs is
      rare. Here, we describe a case of pancreatic adenosquamous carcinoma directly
      invading the spleen and colon in a 44-year-old man. Imaging examinations revealed
      a huge heterogeneous mass in the enlarged spleen and a colonic lump, but showed
      no obvious space-occupying lesion in the pancreas. An exploratory laparotomy
      revealed that the enlarged spleen, pancreatic tail, and splenic flexure of the
      colon were firmly attached to one another. Splenectomy combined with resection of
      the distal pancreas and splenic flexure of the colon was performed. In the distal
      pancreatectomy specimen, a 0.8-cm solid mass was present in the tail. The tumor
      contained definite components of both adenocarcinoma and squamous cell carcinoma.
      The patient died of cachexia five months after admission. This case is unique in
      that the metastatic tumor involving the spleen was considerably larger than the
      primary tumor itself. 

PMID- 23864461
TI  - Isolated dysphagia due to aquaporin-4 autoimmunity.

PMID- 23864462
TI  - The prevalence of CYP2C19 mutations in Turkish patients with dyspepsia and
      influence on H. pylori eradication therapy.

PMID- 23864463
TI  - Capsule retention in stomach due to gastric bezoar in obscure gastrointestinal
      bleeding.

PMID- 23864464
TI  - Gastric metastasis of breast cancer mimicking primary gastric cancer: a case
      report.

PMID- 23864465
TI  - A case of solitary splenic sarcoid reactions with advanced gastric cancer.

PMID- 23864466
TI  - Celiac disease in patient with Turner syndrome.

PMID- 23864467
TI  - Is intensive phototherapy a risk factor for pathogenesis of intussusception?

PMID- 23864468
TI  - Capsule endoscopic appearance of ureteroenteric fistula in obscure
      gastrointestinal bleeding.

PMID- 23864469
TI  - A rare manifestation of celiac disease: mesenteric lymphadenopathy with
      cavitation.

PMID- 23864470
TI  - Cecal duplication cyst presenting as perforation in an adult patient.

PMID- 23864471
TI  - Primary anorectal melanoma.

PMID- 23864472
TI  - Acquisition time: a key point of hepatitis C virus-related liver disease in renal
      transplant recipients.

PMID- 23864473
TI  - Tissue inhibitor of metalloproteinases-1, hyaluronan and chronic hepatitis.

PMID- 23864474
TI  - B-type natriuretic peptide and cirrhosis: is there any relation?

PMID- 23864475
TI  - Cystic hydatid disease of the gallbladder.

PMID- 23864476
TI  - A rare PRSS1 mutation in a Turkish family with hereditary chronic pancreatitis.

PMID- 23864477
TI  - A case of anaplastic carcinoma of pancreas diagnosed with endoscopic ultrasound
      guided fine needle aspiration cytology.

PMID- 23864478
TI  - The vital role of Riolan's arcade as a mesenteric collateral vessel on lower
      extremity perfusion.

PMID- 23864479
TI  - Combinatorial peptide libraries to overcome the classical affinity-enrichment
      methods in proteomics.
AB  - The enrichment of targeted low-abundance proteins is possible by affinity
      adsorption using selected sorbents. Different categories of very dilute proteins
      are present in most of biological extracts so that specific affinity methods are
      unable to address their collective enrichment. Only recently an interesting
      approach has been proposed associating the affinity of multiple ligands used as a
      library mode under overloading much beyond the saturation of the affinity mixed
      bed. The principle and the limits of this technology are reported along with
      their current and potential applications in various domains. 

PMID- 23864480
TI  - Enhancing cerebral oxygenation during blood donation using biofeedback.
AB  - Biofeedback of cerebral oxygenation was used to guide application of applied
      muscle tension during whole blood donation, and resulted in attenuated reductions
      compared to donors who did not receive feedback. 

PMID- 23864481
TI  - Signalling in sarcomeres in development and disease.
AB  - Sarcomeres are the smallest contractile units of heart and skeletal muscles and
      are essential for generation and propagation of mechanical force in these
      striated muscles. During the last decades it has become increasingly clear that
      components of sarcomeres also play a fundamental role in signal transduction in
      physiological and pathophysiological conditions. Mutations or misexpression of
      both sarcomeric contractile and non-contractile proteins have been associated
      with a variety of cardiac diseases. Moreover, re-expression of foetal sarcomeric
      proteins or isoforms during cardiac disease can be observed, emphasising the
      importance of understanding signalling in sarcomeres in both development and
      disease. The prospective of pharmacological intervention at the level of the
      sarcomere is now emerging and may lead to novel therapeutic strategies for the
      treatment of cardiac and skeletal muscle diseases. These aspects will be
      discussed in this brief review and recent findings, which led to novel insights
      into the role of the sarcomeric cytoskeleton in muscle development and disease,
      will be highlighted. 

PMID- 23864482
TI  - Recurrent syncope: a slow heart rate?

PMID- 23864483
TI  - In situ self-folding assembly of a multi-walled hydrogel tube for uniaxial
      sustained molecular release.
AB  - This study presents a multi-walled poly(ethylene glycol) diacrylate hydrogel tube
      formed by the simple self-folding of a bi-layered hydrogel patch. The gel tube
      has the capability to release encapsulated molecules through designated pathways
      in a sustained manner. Therefore, the gel tube encapsulating the vascular
      endothelial growth factor significantly increases the vascular densities and
      vessel diameters at an implantation site. 

PMID- 23864484
TI  - Our future, our heritage. The chemical family tree of Tetsuo Nozoe.

PMID- 23864485
TI  - A new mathematical pharmacodynamic model of clonogenic cancer cell death by
      doxorubicin.
AB  - Previous models for predicting tumor cell growth are mostly based on measurements
      of total cell numbers. The purpose of this paper is to provide a new simple
      mathematical model for calculating tumor cell growth focusing on the fraction of
      cells that is clonogenic. The non-clonogenic cells are considered to be
      relatively harmless. We performed a number of different types of experiments: a
      long-term drug "treatment", several concentrations/fixed time experiments and
      time-series experiments, in which human MCF-7 breast cancer cells were exposed to
      doxorubicin and the total number of cells were counted. In the latter two types,
      at every measurement point a plating efficiency experiment was started. The final
      number of colonies formed is equal to the number of clonogenic cells at the onset
      of the experiment. Based on the intracellular drug concentration, our model
      predicts cell culture effects taking clonogenic ability and growth inhibition by
      neighboring cells into account. The model fitted well to the experimental data.
      The estimated damage parameter which represents the chance of an MCF-7 cell to
      become non-clonogenic per unit time and per unit intracellular doxorubicin
      concentration was found to be 0.0025 +/- 0.0008 (mean +/- SD) nM(-1) h(-1). The
      model could be used to calculate the effect of every doxorubicin concentration
      versus time (C-t) profile. Although in vivo parameters may well be different from
      those found in vitro, the model can be used to predict trends, e.g. by comparing
      effects of different in vivo C-t profiles. 

PMID- 23864486
TI  - Posaconazole therapeutic drug monitoring in the real-life setting: a single
      center experience and review of the literature.
AB  - STUDY OBJECTIVE: To evaluate the incidence of posaconazole serum levels below 700
      MUg/L, the rate of breakthrough infections during posaconazole prophylaxis, and
      factors influencing posaconazole exposure in daily clinical practice. DESIGN:
      Prospective observational study and review of the literature. SETTING: Hematology
      and oncology department in a tertiary care academic medical center. PATIENTS: A
      total of 31 patients with hematologic diseases: 27 received posaconazole
      prophylaxis and 4 received posaconazole therapy. MEASUREMENTS AND MAIN RESULTS:
      We analyzed 187 posaconazole serum levels from 31 patients (median of five
      posaconazole levels per patient; range 1-16). The analyses revealed that 80 of
      187 levels (43%) were below 700 MUg/L, and 68% of patients were found to have at
      least one measured level below this threshold. Breakthrough invasive fungal
      infections categorized as probable or possible infections occurred in 4 of 27
      patients (15%) receiving the drug as prophylaxis. A multivariate analysis,
      accounting for repeated measurements per patient, revealed that age (p=0.02) and
      mucositis (p=0.04) were associated with significantly reduced posaconazole serum
      levels. A review of the current literature on posaconazole therapeutic drug
      monitoring data from real-world studies is presented as an overview table,
      highlighting the frequency of patients with inadequate posaconazole exposure and
      heterogeneity of factors influencing posaconazole levels. CONCLUSION: Therapeutic
      drug monitoring of posaconazole is an important tool of therapy optimization
      because oral posaconazole suspension shows unreliable absorption rates and
      exposure.

PMID- 23864488
TI  - Proceedings of the seventh Northern region paediatric colloquium.
AB  - Ethical and legal dilemmas frequently arise in paediatric practice. Given the
      nature of the speciality, these issues are relevant to both the medical and legal
      professions. To this end, senior figures from the medical and legal professions
      in the Northern region have met on a regular basis in order to discuss anonymised
      case material. We report on the proceedings of the seventh such meeting. Six
      cases are described and key points arising from the subsequent discussion are
      presented.

PMID- 23864487
TI  - The California Breast Cancer Survivorship Consortium (CBCSC): prognostic factors
      associated with racial/ethnic differences in breast cancer survival.
AB  - Racial/ethnic disparities in mortality among US breast cancer patients are well
      documented. Our knowledge of the contribution of lifestyle factors to disease
      prognosis is based primarily on non-Latina Whites and is limited for Latina,
      African American, and Asian American women. To address this knowledge gap, the
      California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled
      interview information (e.g., demographics, family history of breast cancer,
      parity, smoking, alcohol consumption) from six California-based breast cancer
      studies and assembled corresponding cancer registry data (clinical
      characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina
      Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other
      race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and
      2007. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a
      mean (SD) follow-up of 8.3 (3.5) years. Cox proportional hazards regression
      models were fit to data to estimate hazards ratios (HRs) and 95 % confidence
      intervals (CIs) for overall and breast cancer-specific mortality. Compared with
      non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95 % CI
      0.97-1.33) for African Americans, 0.84 (95 % CI 0.70-1.00) for Latinas, and 0.60
      (95 % CI 0.37-0.97) for Asian Americans after adjustment for age, tumor
      characteristics, and select lifestyle factors. The CBCSC represents a large and
      racially/ethnically diverse cohort of breast cancer patients from California.
      This cohort will enable analyses to jointly consider a variety of clinical,
      lifestyle, and contextual factors in attempting to explain the long-standing
      disparities in breast cancer outcomes.

PMID- 23864489
TI  - Reply to letter to the editor: new tendon transfer for correction of drop-foot in
      common peroneal nerve palsy.

PMID- 23864490
TI  - Mortality in high-risk emergency general surgical admissions.
AB  - BACKGROUND: There is increasing evidence of variable standards of care for
      patients undergoing emergency general surgery in the National Health Service
      (NHS). The aim of this study was to quantify and explore variability in mortality
      amongst high-risk emergency general surgery admissions to English NHS hospital
      Trusts. METHODS: The Hospital Episode Statistics (HES) database was used to
      identify high-risk emergency general surgery diagnoses (greater than 5 per cent
      national 30-day mortality rate). Adults admitted to English NHS Trusts with these
      diagnoses between 2000 and 2009 were included in the study. Thirty-day in
      hospital mortality was adjusted for patient and hospital factors. Trusts were
      grouped into high- and low-mortality outliers, and resource availability was
      compared between high- and low-mortality outlier institutions. RESULTS: Some 367
      796 patients admitted to 145 hospital Trusts were included in the study; the 30
      day mortality rate was 15.6 per cent (institutional range 9.2-18.2 per cent).
      Fourteen and 24 hospital Trusts were identified as high- and low-mortality
      outlier institutions respectively. Intensive care and high-dependency bed
      resources, as well as greater institutional use of computed tomography (CT), were
      independent predictors of reduced mortality (P < 0.001). Low-mortality outlying
      Trusts had significantly more intensive care beds per 1000 hospital beds (20.8
      versus 14.0; P = 0.017) and made significantly greater use of CT (24.6 versus
      17.2 scans per bed per year; P < 0.001) and ultrasonography (42.5 versus 30.2
      scans per bed per year; P < 0.001). CONCLUSION: There is significant variability
      in mortality risk between hospital Trusts treating high-risk emergency general
      surgery patients. Equitable access to essential hospital resources may reduce
      variability in outcomes.

PMID- 23864491
TI  - Effect of streptozotocin-induced diabetes on clock gene expression in tissues
      inside and outside the blood-brain barrier in rat.
AB  - The circadian system allows organisms to remain synchronized with rhythmic
      environmental changes with a 24-h period. The molecular mechanism of circadian
      oscillations is based on the rhythmic expression of clock genes organized in
      feedback loops. Alterations in the circadian system contribute to the development
      of several pathological conditions including diabetes, but the exact mechanisms
      responsible for such alterations are not known. Therefore, we employed
      streptozotocin-induced diabetes to elucidate the influence of metabolic changes
      on clock gene (clock, npas2, per2) expression in peripheral oscillators in
      tissues inside (frontal cortex, cerebellum) and outside (heart, kidney) the blood
      brain barrier. Diabetes was induced by streptozotocin injection. Seventeen days
      later, sampling was performed during a 24-h cycle. Gene expression was measured
      using real-time PCR. We observed a phase advance in rhythmic clock gene
      expression in the heart and kidney of diabetic rats. The study also focused on
      the possible role of npas2 in locomotor activity regulation in diabetic animals.
      The most pronounced changes were observed in the frontal cortex, which displayed
      up-regulation of npas2 expression. A change in locomotor activity was observed in
      diabetic rats during the dark phase of the 24-h cycle. We suggest that the
      altered function of the frontal cortex induced by diabetes might contribute to
      the modified behavior of diabetic rats. 

PMID- 23864492
TI  - Influence of 3 months endurance training on red cell deformability in non insulin
      dependent type 2 diabetes mellitus patients.
AB  - The main purpose of the study was to examine if 3 months of bicycle endurance
      training alters the red cell deformability in non insulin dependent type 2
      diabetes mellitus men.The red cell deformability was measured with the Laser
      assisted optical rotational cell analyzer. The maximal elongation index and the
      semimaximal shear stress were measured with the Lineweaver Burke model.At the
      beginning and the end of the intervention the patients passed a bicycle ergometry
      test. As a reference group, 13 males without diabetes passed the same testing
      procedure. Blood samplings were taken before testing, immediately after physical
      exhaustion and after a 30 min recovery phase.After the training period diabetic
      patients could significantly reduce BMI, fasting glucose and HbA1c. The reference
      group had significantly higher elongation indices than the diabetes patients
      independent from training status. After the training period the basal values of
      the maximal elongation index did not change significantly. However, maximal
      elongation indices were significantly reduced after physical examination and in
      resting time.The semimaximal shear stress of diabetes patients did not alter
      during the training period. In comparison to the reference group semimaximal
      shear stress was significantly reduced at all measurement times.This pilot study
      proves that the maximal elongation index is significantly decreased in diabetes
      mellitus patients. After 3 months endurance training the red cells become more
      rigid while the semimaximal shear stress remains constant. Further interventions
      are required to analyze the exact cause of the presented findings. 

PMID- 23864493
TI  - High glucose level induces cardiovascular dysplasia during early embryo
      development.
AB  - The incidence of gestational diabetes mellitus (GDM) has increased dramatically
      amongst multiethnic population. However, how gestational diabetes mellitus
      damages the developing embryo is still unknown. In this study, we used yolk sac
      membrane (YSM) model to investigate angiogenesis in the developing chick embryo.
      We determined that in the presence of high glucose, it retarded the growth and
      extension of the embryonic vascular plexus and it also reduced the density of the
      vasculature in yolk sac membrane model. Using the same strategy, we used the
      chorioallantoic membrane (CAM) as a model to investigate the influence of high
      glucose on the vasculature. We established that high glucose inhibited
      development of the blood vessel plexus and the blood vessels formed had a
      narrower diameter than control vessels. Concurrent with the abnormal
      angiogenesis, we also examined how it impacted cardiogenesis. We determined the
      myocardium in the right ventricle and left atrium were significantly thicker than
      the control and also there was a reduction in glycogen content in cardiomyocytes.
      The high glucose also induced excess reactive oxygen species (ROS) production in
      the cardiomyocytes. We postulated that it was the excess reactive oxygen species
      that damaged the cardiomyocytes resulting in cardiac hyperplasia. 

PMID- 23864494
TI  - Association of cystatin C-based glomerular filtration rate with SYNTAX score in
      patients with diabetes.
AB  - AIM: Serum cystatin C has been proposed as a better marker of glomerular
      filtration rate than serum creatinine. SYNTAX score (SXscore) can accurately
      reflect the severity of coronary artery disease (CAD). However, the association
      between Cystatin C-based glomerular filtration rate (eGFRcys) and SXscore in
      patients with diabetes has never been reported. METHODS: We prospectively
      included 656 consecutive patients with diabetes who were angiographically
      diagnosed with CAD from January 2010 to December 2011. Renal function was
      assessed by eGFRcys. SXscore was calculated using SXscore algorithm. Ordinal
      logistic regression and Pearson correlation were used to analyze the association
      between eGFRcys and SXscore. RESULTS: Patients with renal dysfunction were older,
      more often female, more likely to have a history of hypertension and less tobacco
      use when compared with those patients with normal renal function. Age, sex, SBP,
      DBP, fasting glucose, HbA1c, TC, LDL, HDL, TG, BMI and CRP were not different
      among SXscore tertile groups. Incidence of hypertension, hyperlipidemia, family
      history and tobacco use were similar among these groups. Correlation analysis
      suggested that eGFRcys was negatively correlated with SXscore (R=-0.255,
      P<0.001). Ordinal logistic regression showed that eGFRcys was an independent
      predictor of SXscore (beta=-0.027, P<0.001). CONCLUSIONS: eGFRcys was an
      independent predictor of SXscore in patients with diabetes. This might help
      explain the increased risk of CVD events and mortality in patients with renal
      dysfunction. Further prospectively multiple centre studies are required to better
      quantify this finding.

PMID- 23864495
TI  - Thyroid-stimulating hormone induces the secretion of tumor necrosis factor-alpha
      from 3T3-L1 adipocytes via a protein kinase A-dependent pathway.
AB  - OBJECTIVES: Numerous reports have suggested that thyroid-stimulating hormone
      (TSH) contributes to insulin resistance in adipocytes by directly stimulating the
      production of adipokines, such as tumor necrosis factor alpha (TNF-alpha). The
      objective of this study was to clarify how TSH regulates TNF-alpha secretion in
      3T3-L1 adipocytes and to determine which cell signaling pathways were involved.
      METHODS: Mouse 3T3-L1 preadipocytes were differentiated into adipocytes and then
      exposed to 0.1 mIU/ml bovine TSH. The optimal treatment duration was determined
      by measuring the TNF-alpha concentration in the medium by ELISA. Thereafter,
      adipocytes were treated with 0.01, 0.1, and 1.0 mIU/ml bovine TSH, and the
      optimal TSH dose was determined. To decrease TSHR expression, TSHR shRNA was
      transfected into adipocytes, and the silencing was confirmed by Western blotting.
      The TSH signaling pathways responsible for regulating TNF-alpha secretion were
      studied. Phospho-NF-kappaBp65 Ser276 was quantified by Western blotting, and co
      immunopreci-pitations were performed to detect the formation of the
      IkappaBalpha/PKAc complex. RESULTS: TNF-alpha secretion from adipocytes peaked 4
      h after TSH treatment. TSH induced TNF-alpha secretion in a dose-dependent
      manner, which was almost completely inhibited by TSHR shRNA. There was a
      significant positive correlation between phospho-NF-kappaBp65 Ser276 levels and
      TNF-alpha secretion. H89, a cAMP-dependent protein kinase A inhibitor,
      significantly inhibited the effects of TSH. Bovine TSH and forskolin, which
      increases intracellular cAMP, simultaneously stimulated TNF-alpha secretion. The
      IkappaBalpha/PKAc complex could be detected in TSH-treated cells, but complex
      formation was inhibited by H89. CONCLUSIONS: TSH stimulated the cAMP-PKA pathway
      in 3T3-L1 adipocytes to increase TNF-alpha secretion.

PMID- 23864496
TI  - Automatic face classification of Cushing's syndrome in women - a novel screening
      approach.
AB  - OBJECTIVE: Cushing's syndrome causes considerable harm to the body if left
      untreated, yet often remains undiagnosed for prolonged periods of time. In this
      study we aimed to test whether face classification software might help in
      discriminating patients with Cushing's syndrome from healthy controls. DESIGN:
      Diagnostic study. PATIENTS: Using a regular digital camera, we took frontal and
      profile pictures of 20 female patients with Cushing's syndrome and 40 sex- and
      age-matched controls. MEASUREMENTS: Semi-automatic analysis of the pictures was
      performed by comparing texture and geometry within a grid of nodes placed on the
      pictures. The leave-one-out cross-validation method was employed to classify
      subjects by the software. RESULTS: The software correctly classified 85.0% of
      patients and 95.0% of controls, resulting in a total classification accuracy of
      91.7%. CONCLUSIONS: In this preliminary analysis we found a good classification
      accuracy of Cushing's syndrome by face classification software. Testing accuracy
      is comparable to that of currently employed screening tests.

PMID- 23864497
TI  - Sensitivity analysis of infectious disease models: methods, advances and their
      application.
AB  - Sensitivity analysis (SA) can aid in identifying influential model parameters and
      optimizing model structure, yet infectious disease modelling has yet to adopt
      advanced SA techniques that are capable of providing considerable insights over
      traditional methods. We investigate five global SA methods-scatter plots, the
      Morris and Sobol' methods, Latin hypercube sampling-partial rank correlation
      coefficient and the sensitivity heat map method-and detail their relative merits
      and pitfalls when applied to a microparasite (cholera) and macroparasite
      (schistosomaisis) transmission model. The methods investigated yielded similar
      results with respect to identifying influential parameters, but offered specific
      insights that vary by method. The classical methods differed in their ability to
      provide information on the quantitative relationship between parameters and model
      output, particularly over time. The heat map approach provides information about
      the group sensitivity of all model state variables, and the parameter sensitivity
      spectrum obtained using this method reveals the sensitivity of all state
      variables to each parameter over the course of the simulation period, especially
      valuable for expressing the dynamic sensitivity of a microparasite epidemic model
      to its parameters. A summary comparison is presented to aid infectious disease
      modellers in selecting appropriate methods, with the goal of improving model
      performance and design. 

PMID- 23864498
TI  - Functions of the hydrophilic channels in protonmotive cytochrome c oxidase.
AB  - The structures and functions of hydrophilic channels in electron-transferring
      membrane proteins are discussed. A distinction is made between proton channels
      that can conduct protons and dielectric channels that are non-conducting but can
      dielectrically polarize in response to the introduction of charge changes in
      buried functional centres. Functions of the K, D and H channels found in A1-type
      cytochrome c oxidases are reviewed in relation to these ideas. Possible control
      of function by dielectric channels and their evolutionary relation to proton
      channels is explored. 

PMID- 23864500
TI  - Honeybee combs: how the circular cells transform into rounded hexagons.
AB  - We report that the cells in a natural honeybee comb have a circular shape at
      'birth' but quickly transform into the familiar rounded hexagonal shape, while
      the comb is being built. The mechanism for this transformation is the flow of
      molten visco-elastic wax near the triple junction between the neighbouring
      circular cells. The flow may be unconstrained or constrained by the unmolten wax
      away from the junction. The heat for melting the wax is provided by the 'hot'
      worker bees. 

PMID- 23864499
TI  - Taking a deep look: modern microscopy technologies to optimize the design and
      functionality of biocompatible scaffolds for tissue engineering in regenerative
      medicine.
AB  - This review focuses on modern nonlinear optical microscopy (NLOM) methods that
      are increasingly being used in the field of tissue engineering (TE) to image
      tissue non-invasively and without labelling in depths unreached by conventional
      microscopy techniques. With NLOM techniques, biomaterial matrices, cultured cells
      and their produced extracellular matrix may be visualized with high resolution.
      After introducing classical imaging methodologies such as uCT, MRI, optical
      coherence tomography, electron microscopy and conventional microscopy two-photon
      fluorescence (2-PF) and second harmonic generation (SHG) imaging are described in
      detail (principle, power, limitations) together with their most widely used TE
      applications. Besides our own cell encapsulation, cell printing and collagen
      scaffolding systems and their NLOM imaging the most current research articles
      will be reviewed. These cover imaging of autofluorescence and fluorescence
      labelled tissue and biomaterial structures, SHG-based quantitative morphometry of
      collagen I and other proteins, imaging of vascularization and online monitoring
      techniques in TE. Finally, some insight is given into state-of-the-art three
      photon-based imaging methods (e.g. coherent anti-Stokes Raman scattering, third
      harmonic generation). This review provides an overview of the powerful and
      constantly evolving field of multiphoton microscopy, which is a powerful and
      indispensable tool for the development of artificial tissues in regenerative
      medicine and which is likely to gain importance also as a means for general
      diagnostic medical imaging. 

PMID- 23864501
TI  - Applicability of ToF-SIMS for monitoring compositional changes in bone in a long
      term animal model.
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a well-established
      technique in material sciences but has not yet been widely explored for
      implementation in life sciences. Here, we demonstrate the applicability and
      advantages of ToF-SIMS analysis for the study of minerals and biomolecules in
      osseous tissue. The locally resolved analysis of fragment ions deriving from the
      sample surface enables imaging and differentiation of bone tissue and facilitates
      histology on non-stained cross sections. In a rat model, bilateral ovariectomy
      combined with either a multi-deficiency diet or steroid treatment was carried out
      to create osteoporotic conditions. We focused our study on the Ca content of the
      mineralized tissue and monitored its decline. Calcium mass images of cross
      sections show the progressive degenerative changes in the bone. We observed a
      decreased Ca concentration in the edge region of the trabeculae and a decline in
      the Ca/P ratio. Additionally, we focused on the non-mineralized matrix and
      identified fragment ions that are characteristic for the collagen matrix. We
      observed trabeculae with wide ranges of non-mineralized collagen for the diet
      group owing to an impaired mineralization process. Here, the advantage of coeval
      monitoring of collagen and minerals indicated an osteomalacic model rather than
      an osteoporotic one. 

PMID- 23864502
TI  - Arenavirus budding resulting from viral-protein-associated cell membrane
      curvature.
AB  - Viral replication occurs within cells, with release (and onward infection)
      primarily achieved through two alternative mechanisms: lysis, in which virions
      emerge as the infected cell dies and bursts open; or budding, in which virions
      emerge gradually from a still living cell by appropriating a small part of the
      cell membrane. Virus budding is a poorly understood process that challenges
      current models of vesicle formation. Here, a plausible mechanism for arenavirus
      budding is presented, building on recent evidence that viral proteins embed in
      the inner lipid layer of the cell membrane. Experimental results confirm that
      viral protein is associated with increased membrane curvature, whereas a
      mathematical model is used to show that localized increases in curvature alone
      are sufficient to generate viral buds. The magnitude of the protein-induced
      curvature is calculated from the size of the amphipathic region hypothetically
      removed from the inner membrane as a result of translation, with a change in
      membrane stiffness estimated from observed differences in virion deformation as a
      result of protein depletion. Numerical results are based on experimental data and
      estimates for three arenaviruses, but the mechanisms described are more broadly
      applicable. The hypothesized mechanism is shown to be sufficient to generate
      spontaneous budding that matches well both qualitatively and quantitatively with
      experimental observations. 

PMID- 23864503
TI  - Structuring targeted surveillance for monitoring disease emergence by mapping
      observational data onto ecological process.
AB  - An efficient surveillance system is a crucial factor in identifying, monitoring
      and tackling outbreaks of infectious diseases. Scarcity of data and limited
      amounts of economic resources require a targeted effort from public health
      authorities. In this paper, we propose a mathematical method to identify areas
      where surveillance is critical and low reporting rates might leave epidemics
      undetected. Our approach combines the use of reference-based susceptible-exposed
      infectious models and observed reporting data; We propose two different
      specifications, for constant and time-varying surveillance, respectively. Our
      case study is centred around the spread of the raccoon rabies epidemic in the
      state of New York, using data collected between 1990 and 2007. Both methods offer
      a feasible solution to analyse and identify areas of intervention. 

PMID- 23864504
TI  - Cell-type-specific modelling of intracellular calcium signalling: a urothelial
      cell model.
AB  - Calcium signalling plays a central role in regulating a wide variety of cell
      processes. A number of calcium signalling models exist in the literature that are
      capable of reproducing a variety of experimentally observed calcium transients.
      These models have been used to examine in more detail the mechanisms underlying
      calcium transients, but very rarely has a model been directly linked to a
      particular cell type and experimentally verified. It is important to show that
      this can be achieved within the general theoretical framework adopted by these
      models. Here, we develop a framework designed specifically for modelling
      cytosolic calcium transients in urothelial cells. Where possible, we draw upon
      existing calcium signalling models, integrating descriptions of components known
      to be important in this cell type from a number of studies in the literature. We
      then add descriptions of several additional pathways that play a specific role in
      urothelial cell signalling, including an explicit ionic influx term and an active
      pumping mechanism that drives the cytosolic calcium concentration to a target
      equilibrium. The resulting one-pool model of endoplasmic reticulum (ER)-dependent
      calcium signalling relates the cytosolic, extracellular and ER calcium
      concentrations and can generate a wide range of calcium transients, including
      spikes, bursts, oscillations and sustained elevations in the cytosolic calcium
      concentration. Using single-variate robustness and multivariate sensitivity
      analyses, we quantify how varying each of the parameters of the model leads to
      changes in key features of the calcium transient, such as initial peak amplitude
      and the frequency of bursting or spiking, and in the transitions between bursting
      and plateau-dominated modes. We also show that, novel to our urothelial cell
      model, the ionic and purinergic P2Y pathways make distinct contributions to the
      calcium transient. We then validate the model using human bladder epithelial
      cells grown in monolayer cell culture and show that the model robustly captures
      the key features of the experimental data in a way that is not possible using
      more generic calcium models from the literature. 

PMID- 23864506
TI  - Toxicogenomic evaluation of long-term hepatic effects of TCDD in immature,
      ovariectomized C57BL/6 mice.
AB  - Acute exposure to hepatotoxic doses of 2,3,7,8-tetrachloro- dibenzo-p-dioxin
      (TCDD) in mice is characterized by differential gene expression that can be
      phenotypically anchored to elevated levels of serum alanine aminotransferase,
      increased relative liver weights, hepatic steatosis, inflammation, and
      hepatocellular necrosis. Unlike most studies that focus on acute exposure
      effects, this study evaluated the long-term effects of a single oral gavage of 30
      MUg/kg TCDD at 1, 4, 12, 24, 36, and 72 weeks postdose in ovariectomized C57BL/6
      mice. Hepatic TCDD levels were almost completely eliminated by 24 weeks with a
      calculated half-life of 12 days. Hepatic gene expression analysis identified 395
      unique differentially expressed genes between 1 and 12 weeks that decreased to <=
      8 by 72 weeks, consistent with the minimal hepatic TCDD levels. Hepatic
      vacuolization, characteristic of short-term exposure, subsided by 4 weeks.
      Similarly, TCDD-elicited hepatic necrosis and inflammation dissipated by 1 week.
      Collectively, these results suggest that TCDD-elicited histologic and gene
      expression responses can be correlated to elevated hepatic TCDD levels, which,
      once eliminated, elicit minimal hepatic gene expression and histologic
      alterations. 

PMID- 23864507
TI  - Adherence to dietary recommendations is associated with acculturation among
      Latino farm workers.
AB  - We examined adherence to dietary recommendations on fruit/vegetable and fat
      intake and identified correlates with acculturation indicators as well as with
      family, lifestyle, and occupational factors in a farm worker cohort in central
      California. Interviewer-administered questionnaires for this cross-sectional
      study were completed from January 2006 to April 2007. Participants were 18- to 55
      y-old Latinos living in Mendota in a farm worker household. We assessed
      fruit/vegetable consumption and fat intake using the Block Fruit/Vegetable/Fiber
      Screener and the Block Dietary Fat Screener, respectively. Survey data analysis
      methods for contingency tables and logistic regression were used for assessing
      associations. The sample included 802 participants, reporting mean fruit and
      vegetable intake ( +/- SD) of 5.0 +/- 1.5 daily servings, and 47% reporting < 5
      daily servings. Being born in Mexico or Central America and longer United States
      residency were associated with higher odds of consuming >= 5 daily
      fruit/vegetable servings and more frequent consumption of field products while
      working was associated with lower adherence to this recommendation. The average
      daily percent of calories from fat was 35.0 +/- 4.1% and 53% of participants
      consumed > 35% of daily calories from fat. Men born in Mexico, women born in
      Central America, and participants who worked in fruit or vegetable crops had
      higher odds of consuming <= 35% of calories from fat. Higher acculturation level,
      United States school attendance, and having a child at home were associated with
      lower adherence to this recommendation. Acculturation, family, and occupational
      correlates of diet quality were identified in this underserved, immigrant
      population. Our findings may assist program targeting and intervention efforts. 

PMID- 23864509
TI  - Plant and animal protein intakes are differently associated with nutrient
      adequacy of the diet of French adults.
AB  - The sustainability of dietary plant and animal protein consumption is an
      important issue, but few data are available to ascertain the health-related
      impact of animal and plant protein intake. The objective was to study the
      relationships between animal and plant protein intake and diet quality, as
      reflected by an integrated index of nutrient adequacy. Using data on 1912 adults
      from the French Individual and National Consumption Survey 2 (2006-2007), we
      assessed diet quality by using the PANDiet, a unique score combining 35
      probabilities of having an adequate nutrient intake, and used multiple regression
      analysis to study the relationship with intakes of plant, animal, and related
      food source proteins. After adjustments for intakes of energy, alcohol, and
      protein from other sources and sociodemographic factors, plant protein intake was
      positively associated with the PANDiet, irrespective of sex (beta = 0.50, P <
      0.0001). By contrast, total and animal protein intakes were differently
      associated with the PANDiet according to sex, with a positive association in
      women (beta = 0.07 and beta = 0.08, respectively; P < 0.01) and an inverse
      association in men (beta = -0.07 and beta = -0.05, respectively; P < 0.01). The
      relationships between the PANDiet and intakes of protein from animal food sources
      varied: for instance, associations were inverse for red meat and poultry in men
      but not in women, whereas irrespective of sex, they were positive for fish, milk,
      and yogurt and inverse for processed meat, cheese, and eggs. These findings show
      that plant protein is a robust marker of a healthy diet, whereas total animal
      protein includes different subtypes of animal protein that largely vary in their
      relationship with diet quality. These data could help refine protein
      recommendations from a qualitative and dietary standpoint. 

PMID- 23864510
TI  - The future of recommendations on grain foods in dietary guidance.
AB  - Grain foods serve as an important source of energy, essential nutrients, and
      sometimes fiber. Recognizing that fiber continues to be identified as a nutrient
      of public health priority, there is an urgent need to address the ongoing fiber
      intake deficit. The focus in dietary guidance on whole grains as a source of
      fiber from the grains food group has not improved levels of fiber consumption.
      Consumer confusion around whole grains and fiber, combined with the wide range of
      fiber amounts found in whole-grain-labeled products, suggests that the current
      recommendation to "make half your grains whole" may be oversimplified in its
      intent to support increased fiber intakes. Nutrition educators and policy makers
      need to bring the conversation back to balancing all grain food choices,
      including enriched grains, whole grains, bran-based grain foods, and other grain
      based foods with fiber, with greater emphasis on differentiating grain foods by
      the fiber they deliver. Changes in labeling, policy recommendations, and consumer
      messages are needed to help make this happen. 

PMID- 23864508
TI  - A high-salt diet further impairs age-associated declines in cognitive,
      behavioral, and cardiovascular functions in male Fischer brown Norway rats.
AB  - Aging-associated declines in cognitive, emotional, and cardiovascular function
      are well known. Environmental stress triggers critical changes in the brain,
      further compromising cardiovascular and behavioral health during aging. Excessive
      dietary salt intake is one such stressor. Here, we tested the effect of high salt
      (HS) on anxiety, learning-memory function, and blood pressure (BP) in male
      Fischer brown Norway (FBN) rats. Adult (A; 2 mo) and old (O; 20 mo) male rats
      were fed normal-salt (NS; 0.4% NaCl) or HS (8% NaCl) diets for 4 wk after being
      implanted with telemeter probes for conscious BP measurement. Thereafter, tests
      to assess anxiety-like behavior and learning-memory were conducted. The rats were
      then killed, and samples of plasma, urine, and brain tissue were collected. We
      found that systolic BP was higher in O-NS (117 +/- 1.2 mm Hg) than in A-NS (105
      +/- 0.8 mm Hg) rats (P < 0.05). Furthermore, BP was higher in O-HS (124 +/- 1.4
      mm Hg) than in O-NS (117 +/- 1.2 mm Hg) rats (P < 0.05). Moreover, anxiety-like
      behavior (light-dark and open-field tests) was not different between A-NS and O
      NS rats but was greater in O-HS rats than in A-NS, O-NS, or A-HS rats (P < 0.05).
      Short-term memory (radial arm water maze test) was similar in A-NS and O-NS rats
      but was significantly impaired in O-HS rats compared with A-NS, O-NS, or A-HS
      rats (P < 0.05). Furthermore, oxidative stress variables (in plasma, urine, and
      brain) as well as corticosterone (plasma) were greater in O-HS rats when compared
      with A-NS, O-NS, or A-HS rats (P < 0.05). The antioxidant enzyme glyoxalase-1
      expression was selectively reduced in the hippocampus and amygdala of O-HS rats
      compared with A-NS, O-NS, or A-HS rats (P < 0.05), whereas other antioxidant
      enzymes, glutathione reductase 1, manganese superoxide dismutase (SOD), and Cu/Zn
      SOD remained unchanged. We suggest that salt-sensitive hypertension and
      behavioral derangement are associated with a redox imbalance in the brain of aged
      FBN rats. 

PMID- 23864511
TI  - A food store-based environmental intervention is associated with reduced BMI and
      improved psychosocial factors and food-related behaviors on the Navajo nation.
AB  - The prevalence of obesity is significantly higher among American Indians (AIs)
      and is associated with increased rates of diabetes, hypertension, and
      cardiovascular disease. We implemented a 14-mo intervention trial (Navajo Healthy
      Stores) on the Navajo Nation that sought to increase availability of healthier
      foods in local food stores and to promote these foods at the point of purchase
      and through community media. We divided the Navajo Nation into 10 store regions,
      half of which were randomized to intervention and half to comparison. We
      evaluated the program by using a pre-post sample of systematically sampled adult
      Navajo consumers (baseline, n = 276; postintervention, n = 145). Intervention
      impact was examined by analyzing pre-post differences by intervention group and
      by intervention exposure level. When intervention and comparison groups were
      compared, only body mass index (BMI) showed a trend toward impact of the
      intervention (P = 0.06). However, greater exposure to the intervention was
      associated with significantly reduced BMI (P <= 0.05) and improved healthy food
      intentions (P <= 0.01), healthy cooking methods (P <= 0.05), and healthy food
      getting (P <= 0.01). With increasing exposure, the odds of improving overweight
      or obese status was 5.02 (95% CI: 1.48, 16.99; P <= 0.01) times the odds of
      maintaining or worsening overweight or obese status. In summary, a food store
      intervention was associated with reduced overweight/obesity and improved obesity
      related psychosocial and behavioral factors among those persons most exposed to
      the intervention on an AI reservation. 

PMID- 23864513
TI  - Cytochrome c and superoxide.
AB  - Wegerich et al. (J. Biol. Inorg. Chem. 18:429-440, 2013), working with singly
      modified human cytochromes c, claim to have found a new mechanism for the
      reduction of iron(III) cytochrome c by superoxide. I show that electron transfer
      by way of the solvent-accessible haem edge-a mechanism not considered by Wegerich
      et al.-is still the correct mechanism. Furthermore, several deficiencies in this
      work preclude any comparisons with other publications on this topic.

PMID- 23864512
TI  - n3 PUFAs reduce mouse CD4+ T-cell ex vivo polarization into Th17 cells.
AB  - Little is known about the impact of n3 (omega3) PUFAs on polarization of CD4(+) T
      cells into effector subsets other than Th1 and Th2. We assessed the effects of
      dietary fat [corn oil (CO) vs. fish oil (FO)] and fermentable fiber [cellulose
      (C) vs. pectin (P)] (2 * 2 design) in male C57BL/6 mice fed CO-C, CO-P, FO-C, or
      FO-P diets for 3 wk on the ex vivo polarization of purified splenic CD4(+) T
      cells (using magnetic microbeads) into regulatory T cells [Tregs; forkhead box P3
      (Foxp3(+)) cells] or Th17 cells [interleukin (IL)-17A(+) and retinoic acid
      receptor-related orphan receptor (ROR) gammatau(+) cells] by flow cytometry. Treg
      polarization was unaffected by diet; however, FO independently reduced the
      percentage of both CD4(+) IL-17A(+) (P < 0.05) and CD4(+) RORgammatau(+) cells (P
      < 0.05). Moreover, expression of another critical Th17-cell-related transcription
      factor, signal transducer and activator of transcription 3, was reduced by FO.
      Dietary FO reduced the surface expression of both IL-6R and IL-23R on polarized
      Th17 cells (P <= 0.05), thus interfering with the promotive effects of these
      critical cytokines on Th17 polarization. Additionally, C57BL/6 mice fed diets
      enriched in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or DHA + EPA
      similarly reduced Th17-cell polarization in comparison to CO by reducing
      expression of the Th17-cell signature cytokine (IL-17A; P = 0.0015) and
      transcription factor (RORgammatau P = 0.02), whereas Treg polarization was
      unaffected. Collectively, these data show that n3 PUFAs exert a direct effect on
      the development of Th17 cells in healthy mice, implicating a novel n3 PUFA
      dependent, anti-inflammatory mechanism of action via the suppression of the
      initial development of this inflammatory T-cell subset. 

PMID- 23864514
TI  - Effect of whole-body vibration exercise on mobility, balance ability and general
      health status in frail elderly patients: a pilot randomized controlled trial.
AB  - OBJECTIVE: To study the effects of whole-body vibration exercises on the mobility
      function, balance and general health status, and its feasibility as an
      intervention in frail elderly patients. DESIGN: Pilot randomized controlled
      trial. SUBJECTS: Forty-four frail older persons (85.27 +/- 3.63 years) meeting
      the Fried Frailty Criteria. INTERVENTIONS: All eligible subjects were randomly
      assigned to the experimental group, who received a whole-body vibration exercise
      alone (vibration amplitude: 1-3 mm; frequency: 6-26 Hz; 4-5 bouts * 60 seconds; 3
      5 times weekly), or a control group, who received usual care and exercises for
      eight weeks. MAIN MEASURES: The Timed Up and Go Test, 30-second chair stand test,
      lower extremities muscle strength, balance function, balance confidence and
      General Health Status were assessed at the beginning of the study, after four
      weeks and eight weeks of the intervention. RESULTS: Whole-body vibration exercise
      reduced the time of the Timed Up and Go Test (40.47 +/- 15.94 s to 21.34 +/- 4.42
      s), improved the bilateral knees extensor strength (6.96 +/- 1.70 kg to 11.26 +/-
      2.08 kg), the posture stability (surface area ellipse: 404.58 +/- 177.05 to
      255.95 +/- 107.28) and General Health Status (Short-form Health Survey score:
      24.51 +/- 10.69 and 49.63 +/- 9.85 to 45.03 +/- 11.15 and 65.23 +/- 9.39,
      respectively). The repeated-measures ANOVA showed that there were significant
      differences in the Timed Up and Go Test, 30-second chair stand test, bilateral
      knees extensor strength, activities-specific balance confidence score and general
      health status between the two groups (P < 0.05). No side-effects were observed
      during the training. CONCLUSIONS: Whole-body vibration exercise is a safe and
      effective method that can improve the mobility, knee extensor strength, balance
      and the general health status in the frail elderly.

PMID- 23864515
TI  - Functional and psychosocial effects of either a traditional dancing or a formal
      exercising training program in patients with chronic heart failure: a comparative
      randomized controlled study.
AB  - OBJECTIVE: To compare the effects of traditional dancing with formal exercise
      training in terms of functional and cardiovascular benefits and motivation in
      patients with chronic heart failure. DESIGN: Randomized controlled trial.
      SETTING: Sports Medicine Laboratory. SUBJECTS: Fifty-one Greek male patients aged
      67.1+/-5.5 years with chronic heart failure of New York Heart Association (NYHA)
      class II-III, participated in an eight-month study. INTERVENTIONS: They were
      randomly assigned to either training with Greek traditional dances (group A,
      n=18), formal exercise training (group B, n=16) or a sedentary control group
      (group C, n=17). MAIN MEASURES: At entry and the end of the study all patients
      underwent cardiopulmonary exercise testing, functional ability assessment and
      quality of life evaluations. The Intrinsic Motivation Inventory was also used to
      assess participants' subjective experience. RESULTS: After training group A
      showed increased peak oxygen consumption by 33.8% (19.5 vs. 26.1 ml/kg/min,
      p<0.05) and B by 32.3% (19.5 vs. 25.8 ml/kg/min, p<0.05), maximal treadmill
      tolerance by 48.5% (p<0.05) and by 46.4% (p<0.05), and a decreased Slope of
      expired minute ventilation for carbon dioxide output (VE/VCO2) slope by 18%
      (p<0.05) and 19.5% (p<0.05), respectively. Trained patients revealed significant
      improvement in the quality of life indices. Intrinsic Motivation Inventory was
      increased only in group A by 26.2% (3.08 vs. 3.87, p<0.05). CONCLUSIONS: Exercise
      training in chronic heart failure patients with Greek traditional dances led to
      functional and cardiovascular benefits similar to formal exercise training and to
      a higher level of motivation.

PMID- 23864516
TI  - Randomized controlled pilot study of customized pamphlets to promote physical
      activity and symptom self-management in women with multiple sclerosis.
AB  - OBJECTIVE: Investigate the feasibility and potential efficacy of a customized
      print-based intervention to promote physical activity and symptom self-management
      in women with multiple sclerosis. DESIGN: A randomly allocated two-group repeated
      measures design, with a delayed-treatment contact group serving as the control.
      Participants were randomized to receive the intervention immediately (n =14) or
      receive it at week 12 (n =16). Outcome measures were administered at weeks 1, 12,
      and 24. SETTING: Community-based in metropolitan area. SUBJECTS: Thirty women
      with multiple sclerosis. INTERVENTION: Prescribing a home-exercise program and
      following up with customized pamphlets, which are matched to participants' stage
      of readiness to change physical activity behavior and physical activity barriers
      (e.g. encouraging self-management of symptoms). MAIN MEASURES: Physical Activity
      and Disability Survey-revised, Godin Leisure-Time Exercise Questionnaire, SF-12,
      Symptoms of Multiple Sclerosis Scale, and 6-minute walk test. RESULTS: Intent-to
      treat analyses using mixed multivariate analysis of variance (MANOVA) were
      conducted on (1) physical activity levels and (2) health and function outcomes.
      The mixed MANOVAs for physical activity levels and health and function outcomes
      indicated significant improvements in the immediate group compared with the
      delayed group (i.e. condition by time interaction was significant, Wilks' lambda
      = 0.59, F(2, 27) = 9.31, P = 0.001 and Wilks' lambda = 0.70, F(4, 25) = 2.72, P =
      0.052, respectively). The intervention had moderate to large effect sizes in
      improving physical activity levels (d = 0.63 to 0.89), perceptions of physical
      function (d = 0.63), and 6-minute walk test (d=0.86). CONCLUSION: This pilot
      study indicates that a customized print-based intervention shows promise in
      improving physical activity levels and health and function in women with multiple
      sclerosis.

PMID- 23864517
TI  - An occupation-based strategy training approach to managing age-related executive
      changes: a pilot randomized controlled trial.
AB  - OBJECTIVE: To determine the feasibility of recruitment and retention of healthy
      older adults and the effectiveness of an intervention designed to manage age
      related executive changes. DESIGN: A pilot randomized controlled trial. SETTING:
      Research centre and participants' homes. PARTICIPANTS: Nineteen healthy,
      community dwelling older adults with complaints of cognitive difficulties and
      everyday problems, but no evidence of mild cognitive impairment, dementia or
      depression on objective testing. INTERVENTIONS: Seventeen hours of group and
      individual training. Participants in the experimental arm received education
      about self-management, successful aging and an occupation-based meta-cognitive
      strategy-training program. Participants in the control arm received education
      about brain health and participated in cognitively stimulating exercises. MAIN
      MEASURES: Changes on untrained, everyday life goals were identified using the
      Canadian Occupational Performance Measure. Generalization of benefits was
      measured using the Stanford Chronic Disease Questionnaire, general self-efficacy
      and changes in executive function (Delis-Kaplan Executive Function System Tower
      Test, Word Fluency and Trail-Making Test). RESULTS: 20% (19/96) of healthy older
      adults approached were eligible, consented and were enrolled in the study, 90%
      (17/19) were retained to three-month follow-up. Participants in the experimental
      arm reported significantly more improvement on untrained goals (11/22 compared
      with 9/46, chi(2)=4.92, p<0.05), maintenance of physical activity (p<0.05) and
      better preparation for doctors' visits (p<0.05) relative to the control group.
      There were no significant between group differences on objective measures of
      executive function. CONCLUSIONS: These data support the feasibility of a larger
      trial where a sample of 72 (36 participants in each arm) would be required to
      confirm or refute these findings.

PMID- 23864518
TI  - The efficacy of Botulinum Toxin A for spasticity and pain in adults: a systematic
      review and meta-analysis using the Grades of Recommendation, Assessment,
      Development and Evaluation approach.
AB  - OBJECTIVES: A systematic review and meta-analysis using the Grades of
      Recommendation, Assessment, Development and Evaluation (GRADE) approach to
      evaluate Botulinum Toxin Type A efficacy on spasticity and pain in the
      upper/lower limb in adults. DATA SOURCES: Pubmed, Cinahl, Amed, Embase and
      Cochrane Databases. English language. 1989 to April 2013. REVIEW METHODS: All
      randomized controlled trials on adults with spasticity of any origin in the upper
      or lower limb, treated with a single dose of Botulinum Toxin A, with outcome
      measures for pain or spasticity. Quality was assessed by GRADE, which uses a
      transparent, structured process for developing and presenting summaries of
      evidence, including its quality, for systematic reviews. RESULTS: A total of 37
      studies were reviewed. A meta-analysis was carried out on 10 for pain and 21 for
      spasticity. Evidence quality was low/very low for pain. No significant effect was
      found in the upper limb (standardised mean difference (SMD) = 0.44, confidence
      interval (CI) -0.02 to 0.90, Z = 1.88, P=0.06), and no effect was found in the
      lower limb (risk ratio (RR) = 1.01 CI 0.19 to 5.36, Z = 0.02, P=0.99). Evidence
      quality for spasticity was moderate. Significant effects were found for Botulinum
      Toxin in the upper limb (weighted mean difference (WMD) = 0.88, CI 0.63 to 1.14,
      Z = 6.86, P<0.00001), and the lower limb (RR=2.42, CI 1.60 to 3.65, Z=4.18,
      P<0.0001). CONCLUSION: The use of Botulinum Toxin A is supported for upper and
      lower limb spasticity. Further evidence is needed for spasticity-related pain.
      Evidence quality is reduced by inadequate study design.

PMID- 23864519
TI  - Fabrication and characterization of magnetic microrobots for three-dimensional
      cell culture and targeted transportation.
AB  - Magnetically manipulated microrobots are demonstrated for targeted cell
      transportation. Full three-dimensional (3D) porous structures are fabricated with
      an SU-8 photoresist using a 3D laser lithography system. Nickel and titanium are
      deposited as a magnetic material and biocompatible material, respectively. The
      fabricated microrobots are controlled in the fluid by external magnetic fields.
      Human embryonic kidney 239 (HEK 239) cells are cultivated in the microrobot to
      show the possibility for targeted cell transportation. 

PMID- 23864520
TI  - [Adult attention deficit/hyperactivity disorder, associated symptoms and comorbid
      psychiatric disorders: diagnosis and pharmacological treatment].
AB  - Adult attention deficit/hyperactivity disorder (ADHD) is characterised by
      inattention and/or hyperactivity and impulsivity and is a frequent psychiatric
      disorder with childhood onset. In addition to core symptoms, patients often
      experience associated symptoms like emotional dysregulation or low self-esteem
      and suffer from comorbid disorders, particularly depressive episodes, substance
      abuse, anxiety or sleep disorders. It is recommended to include associated
      symptoms and comorbid psychiatric disorders in the diagnostic set-up and in the
      treatment plan. Comorbid psychiatric disorders should be addressed with disorder
      specific therapies while associated symptoms also often improve with treatment of
      the ADHD core symptoms. The most impairing psychiatric disorder should be treated
      first. This review presents recommendations for differential diagnosis and
      treatment of adult ADHD with associated symptoms and comorbid psychiatric
      disorders with respect to internationally published guidelines, clinical trials
      and expert opinions. 

PMID- 23864521
TI  - Not my fault: blame externalization is the psychopathic feature most associated
      with pathological delinquency among confined delinquents.
AB  - The association between psychopathy and crime is established, but the specific
      components of the personality disorders that most contribute to crime are largely
      unknown. Drawing on data from 723 confined delinquents in Missouri, the present
      study delved into the eight subscales of the Psychopathic Personality Inventory
      Short Form to empirically assess the specific aspects of the disorder that are
      most responsible for explaining variation in career delinquency. Blame
      externalization emerged as the strongest predictor of career delinquency in
      ordinary least squares regression, logistic regression, and t-test models.
      Fearlessness and carefree nonplanfulness were also significant in all models.
      Other features of psychopathy, such as stress immunity, social potency, and
      coldheartedness were weakly and inconsistently predictive of career delinquency.
      Implications of these findings for the study of psychopathy and delinquent
      careers are discussed in this article. 

PMID- 23864522
TI  - An empirical assessment of the overlap between sexual victimization and sex
      offending.
AB  - There has been a recent proliferation in the number of studies that are
      investigating the phenomenon that has been coined the victim-offender overlap.
      There has been noticeably less attention toward examining the sexual
      victimization and sex offending overlap. Acknowledging this gap in the
      literature, the present study provides an assessment of this overlap among a
      large sample of male prisoners with a focus on the cycle of violence hypothesis.
      Bivariate results reveal a considerable degree of overlap between sexual
      victimization and sex offending, and multivariate results estimated from a series
      of bivariate probit models simultaneously assessing both outcomes suggest that
      experiencing emotional abuse early on in the life-course is a robust risk factor
      for experiencing sexual victimization and demonstrating sex offending behavior.
      Furthermore, being physically neglected and witnessing family violence also
      emerged as significant risk factors for sexual victimization. Study limitations
      and policy implications are also discussed. 

PMID- 23864523
TI  - An exploration of the latent constructs of the STATIC-99.
AB  - Although actuarial instruments are ubiquitously used in the field of sex offender
      recidivism risk assessment, there is limited empirical information about the
      underlying constructs from which they are derived. The following study utilized a
      nonparametric item response theory procedure, a Mokken analysis, and nonlinear
      factor analysis (Normal Ogive Harmonic Analysis Robust Method) to explore the
      underlying constructs of the STATIC-99 scores obtained for male sexual offenders
      (N = 451) referred for an evaluation to determine if they met criteria for civil
      commitment under a state's Sexually Violent Persons Law. The results from the
      analyses indicated that the STATIC-99 comprises the two previously identified
      constructs associated with sexual deviancy and antisocial behaviors as well as a
      third, additional construct, associated with the items pertaining to age and past
      marital-type relationships. These findings support Hanson and Thornton's
      assertion that sexual offender recidivism risk is multifactorial and not the
      result of a single underlying trait. Implications for future research are
      discussed.

PMID- 23864524
TI  - An examination of the interrater reliability between practitioners and
      researchers on the static-99.
AB  - Many studies have validated the psychometric properties of the Static-99, the
      most widely used measure of sexual offender recidivism risk. However much of this
      research relied on instrument coding completed by well-trained researchers. This
      study is the first to examine the interrater reliability (IRR) of the Static-99
      between practitioners in the field and researchers. Using archival data from a
      sample of 1,973 formerly incarcerated sex offenders, field raters' scores on the
      Static-99 were compared with those of researchers. Overall, clinicians and
      researchers had excellent IRR on Static-99 total scores, with IRR coefficients
      ranging from "substantial" to "outstanding" for the individual 10 items of the
      scale. The most common causes of discrepancies were coding manual errors,
      followed by item subjectivity, inaccurate item scoring, and calculation errors.
      These results offer important data with regard to the frequency and perceived
      nature of scoring errors.

PMID- 23864525
TI  - Blood pressure regulation VII. The "morning surge" in blood pressure: measurement
      issues and clinical significance.
AB  - In keeping with this review-series theme, we question whether the morning surge
      in blood pressure (MSBP) is a benign response to the physiological challenges
      during the first 3 h after waking, or is it clinically important? Therefore, we
      scrutinise the circadian-related mechanisms, the measurement methods and the
      prognostic value of the MSBP. The MSBP is relatively small (<2 mmHg) under
      constant routine conditions. Nevertheless, the blood pressure response to
      exercise can be 8-14 mm Hg greater in the morning vs. afternoon, even when prior
      sleep is controlled. Systematic bias between MSBP methods can be >10 mmHg. The
      "sleep-trough" method provides the largest MSBP (~25 mmHg), but the sensitivity
      of MSBP to a treatment/intervention depends largely on its repeatability. The
      repeatability standard deviation (SD) for most MSBP methods is ~8 mm Hg. While
      the magnitude of this SD precludes the use of MSBP for diagnostic decisions on
      individual patients, sample sizes for future intervention studies may be
      feasible, depending on the minimal clinically important difference in MSBP. This
      difference is somewhat unclear given that a large MSBP has recently been reported
      to predict a reduced, rather than a higher, risk of cardiovascular disease,
      although this particular study has been criticised. The MSBP is also naturally
      correlated to changes in physical activity and nocturnal "dipping" status.
      Therefore, it is important to account for these potential confounders of the
      MSBP, so that more precise knowledge about its clinical significance is gained,
      thereby providing a sound rationale for physiological investigation and
      translational research.

PMID- 23864526
TI  - Retrograde blood flow in the inactive limb is enhanced during constant-load leg
      cycling in hypoxia.
AB  - PURPOSE: This study aimed to elucidate the effects of hypoxia on the pattern of
      oscillatory blood flow in the inactive limb during constant-load dynamic
      exercise. We hypothesised that retrograde blood flow in the brachial artery of
      the inactive limb would increase during constant-load leg cycling under hypoxic
      conditions. METHODS: Three maximal exercise tests were conducted in eight healthy
      males on a semi-recumbent cycle ergometer while the subjects breathed a normoxic
      [inspired oxygen fraction (FIO2) = 0.209] or two hypoxic gas mixtures (FIO2 =
      0.155 and 0.120). Subjects then performed submaximal exercise at the same
      relative exercise intensity of 60 % peak oxygen uptake under normoxic or the two
      hypoxic conditions for 30 min. Brachial artery blood velocity and diameter were
      recorded simultaneously during submaximal exercise using Doppler ultrasonography.
      RESULTS: Antegrade blood flow gradually increased during exercise, with no
      significant differences among the three trials. Retrograde blood flow showed a
      biphasic response, with an initial increase followed by a gradual decrease during
      normoxic exercise. In contrast, retrograde blood flow significantly increased
      during moderate and severe hypoxic exercise, and remained elevated above normoxic
      conditions during exercise. At 30 min of exercise, the magnitude of the change in
      retrograde blood flow during exercise was greater as the level of hypoxia
      increased (normoxia: -18.7 +/- 23.5 ml min(-1); moderate hypoxia: -39.3 +/- 21.4
      ml min(-1); severe hypoxia: -64.0 +/- 36.3 ml min(-1)). CONCLUSION: These results
      indicate that moderate and severe hypoxia augment retrograde blood flow in the
      inactive limb during constant-load dynamic leg exercise.

PMID- 23864527
TI  - Feasibility of implementing a comprehensive warfarin pharmacogenetics service.
AB  - STUDY OBJECTIVE: To determine the procedural feasibility of a pharmacist-led
      interdisciplinary service for providing genotype-guided warfarin dosing for
      hospitalized patients newly starting warfarin. DESIGN: Prospective observational
      study. SETTING: A 438-bed tertiary care hospital affiliated with a large academic
      institution. PATIENTS: Eighty patients who started warfarin therapy and were
      managed by a newly implemented pharmacogenetics service. INTERVENTION: All
      patients received routine warfarin genotyping and clinical pharmacogenetics
      consultation. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were percentage
      of genotype-guided dose recommendations available prior to the second warfarin
      dose and adherence of the medical staff to doses recommended by the
      pharmacogenetics service. Of 436 genotype orders placed during the first 6 months
      of the service, 190 (44%) were deemed appropriate. For the 80 patients on the
      service who consented to data collection, 76% of the genotypes were available
      prior to the second warfarin dose. The median (range) time from genotype order to
      genotype result was 26 hours (7-80 hrs), and the time to genotype-guided dose
      recommendation was 30 hours (7-80 hrs). A total of 73% of warfarin doses ordered
      by the medical staff were within 0.5 mg of the daily dose recommended by the
      pharmacogenetics consult service. CONCLUSION: Providing routine genotype-guided
      warfarin dosing supported by a pharmacogenetics consult service is feasible from
      a procedural standpoint, with most genotypes available prior to the second
      warfarin dose and good adherence to genotype-guided dose recommendations by the
      medical staff.

PMID- 23864528
TI  - Green tea catechins prevent obesity through modulation of peroxisome proliferator
      activated receptors.
AB  - Epidemiological evidence and experimental studies suggest that drinking green tea
      is associated with a lower risk of obesity and related diseases. However, the
      mechanisms of these effects are not clear. In the present study, we investigated
      the anti-obesity mechanisms of green tea catechins (GTCs) through modulation of
      peroxisome proliferator activated-receptor (PPAR) pathways in high-fat diet
      induced obesity in rats. GTC supplementation significantly attenuated the
      increased body and liver weights and the elevated serum and liver triglyceride
      levels. Meanwhile, GTCs increased the PPARgamma levels in subcutaneous white
      adipose tissue (SWAT) and decreased the PPARgamma levels in visceral white
      adipose tissue (VWAT). In addition, GTC treatment up-regulated the levels of
      PPARdelta in SWAT, VWAT, and brown adipose tissue and increased the expression of
      genes involved in fatty acid oxidation in brown adipose tissue. Our results
      suggest that GTCs exert their anti-obesity mechanism in part by modulating PPAR
      signaling pathways.

PMID- 23864529
TI  - The twin-arginine subunit C in Oscarella: origin, evolution, and potential
      functional significance.
AB  - The twin-arginine translocation (Tat) pathway is a protein transport system that
      moves completely folded proteins across lipid membranes. Genes encoding
      components of the pathway have been found in the genomes of many Bacteria,
      Archaea, and eukaryotic organelles including chloroplasts, plant mitochondria,
      and the mitochondria of many protists. However, with a single exception, Tat
      genes are absent from the mitochondrial genomes of all animals. The only
      exception comes from the homoscleromorph sponges in the family Oscarellidae,
      whose mitochondrial genomes encode a gene for tatC, the largest subunit of the
      complex. Here, we explore the origin and evolution of the mitochondrial tatC gene
      in Oscarellidae, and use bioinformatic approaches to evaluate its functional
      significance. We conclude that tatC in Homoscleromorpha sponges was likely
      inherited from the ancestral proto-mitochondrial genome, implying multiple
      independent losses of the mitochondrial Tat pathway during the evolution of
      opisthokonts. In addition, bioinformatic evidence suggests that tatC comprises
      the entire Tat pathway in Oscarellidae, and that the Rieske Fe/S protein of
      mitochondrial complex III is its likely substrate. 

PMID- 23864531
TI  - Super-resolution nonlinear photothermal microscopy.
AB  - Super-resolution fluorescence microscopy enables imaging of fluorescent
      structures beyond the diffraction limit. However, this technique cannot be
      applied to weakly fluorescent cellular components or labels. As an alternative,
      photothermal microscopy based on nonradiative transformation of absorbed energy
      into heat has demonstrated imaging of nonfluorescent structures including single
      molecules and ~1-nm gold nanoparticles. However, previously photothermal imaging
      has been performed with a diffraction-limited resolution only. Herein, super
      resolution, far-field photothermal microscopy based on nonlinear signal
      dependence on the laser energy is introduced. Among various nonlinear phenomena,
      including absorption saturation, multiphoton absorption, and signal temperature
      dependence, signal amplification by laser-induced nanobubbles around overheated
      nano-objects is explored. A Gaussian laser beam profile is used to demonstrate
      the image spatial sharpening for calibrated 260-nm metal strips, resolving of a
      plasmonic nanoassembly, visualization of 10-nm gold nanoparticles in graphene,
      and hemoglobin nanoclusters in live erythrocytes with resolution down to 50 nm.
      These nonlinear phenomena can be used for 3D imaging with improved lateral and
      axial resolution in most photothermal methods, including photoacoustic
      microscopy. 

PMID- 23864530
TI  - How will telomeric complex be further contributed to our longevity? - the
      potential novel biomarkers of telomere complex counteracting both aging and
      cancer.
AB  - With the smooth move towards the coming expected clinical reports of anticancer
      pharmaceutical molecules targeting telomeres and telomerase, and also with the
      exciting success in the extension of lifespan by regulating telomerase activity
      without increased onset of oncogenesis in laboratory mouse models (Garcia-Cao et
      al., 2006; Jaskelioff et al., 2011), we are convinced that targeting telomeres
      based on telomerase will be a potential approach to conquer both aging and cancer
      and the idea of longevity seems to be no more mysterious. More interestingly,
      emerging evidences from clinical research reveal that other telomeric factors,
      like specific telomeric binding proteins and nonspecific telomere associated
      proteins also show crucial importance in aging and oncogenesis. This stems from
      their roles in the stability of telomere structure and in the inhibition of DNA
      damage response at telomeres. Uncapping these proteins from chromosome ends leads
      to dramatic telomere loss and telomere dysfunction which is more abrupt than
      those induced by telomerase inactivation. Abnormal expression of these factors
      results in developmental failure, aging and even oncogenesis evidenced by several
      experimental models and clinical cases, indicating telomere specific proteins and
      its associated proteins have complimentary roles to telomerase in telomere
      protection and controlling cellular fate. Thus, these telomeric factors might be
      potential clinical biomarkers for early detection or even therapeutic targets of
      aging and cancer. Future studies to elucidate how these proteins function in
      telomere protection might benefit patients suffering aging or cancer who are not
      sensitive to telomerase mediation. 

PMID- 23864532
TI  - Evaluation of AlloMax acellular dermal matrix for objective collagen deposition.
AB  - Acellular dermal matrix products are popular in various aspects of surgical
      reconstruction including hernia repairs and breast reconstructions. The goal of
      this study was to determine quantitative collagen weights of AlloMax (C. R. Bard,
      Inc. [Davol], Warwick, RI) and of contralateral dermis for composition
      comparison. A rehydrated sample of AlloMax was subcutaneously implanted on the
      dorsum of 18 male Wistar rats. Rats were randomly assigned to groups on the basis
      of in vivo implant time: 1, 3, and 6 weeks. At the end of the implant time, the
      AlloMax was removed and a section of contralateral dermis was excised as a
      control. Hydroxyproline, rat Collagen I and Collagen III, and neoangiogenesis
      were determined in the sections. The results are reported as mean +/- standard
      error of the mean. Analysis of variance was used to evaluate the between-group
      differences. A p value of 0.05 or less was considered significant. Hydroxyproline
      was significantly increased in the 6-week AlloMax implant (26.19 +/- 1.05 vs.
      15.03 +/- 3.29). Collagen I and Collagen III were significantly increased
      following 3 weeks in vivo (612.5% +/- 98.0 vs. 312.9% +/- 82.7, p < 0.05 Collagen
      I). Neoangiogenesis was significantly increased at 3 and 6 weeks in vivo (2.3 +/-
      0.3 and 1.9 +/- 0.3). Acellular AlloMax was rapidly incorporated into the rat
      dorsum. The measurement parameters were greater than or equivalent to
      contralateral dermis in this study.

PMID- 23864533
TI  - Comment on high-efficiency panchromatic hybrid Schottky solar cells.

PMID- 23864534
TI  - Is the treatment of the small saphenous veins with foam sclerotherapy at risk of
      deep vein thrombosis?
AB  - OBJECTIVE: To assess the deep vein thrombosis risk of the treatment of the small
      saphenous veins depending on the anatomical pattern of the veins. METHOD: A
      multicenter, prospective and controlled study was carried out in which small
      saphenous vein trunks were treated with ultrasound-guided foam sclerotherapy. The
      anatomical pattern (saphenopopliteal junction, perforators) was assessed by
      Duplex ultrasound before the treatment. All patients were systematically checked
      by Duplex ultrasound 8 to 30 days after the procedure to identify a potential
      deep vein thrombosis. RESULTS: Three hundred and thirty-one small saphenous veins
      were treated in 22 phlebology clinics. No proximal deep vein thrombosis occurred.
      Two (0.6%) medial gastrocnemius veins thrombosis occurred in symptomatic
      patients. Five medial gastrocnemius veins thrombosis and four cases of extension
      of the small saphenous vein sclerosis into the popliteal vein, which all occurred
      when the small saphenous vein connected directly into the popliteal vein, were
      identified by systematic Duplex ultrasound examination in asymptomatic patients.
      Medial gastrocnemius veins thrombosis were more frequent (p = 0.02) in patients
      with medial gastrocnemius veins perforator. A common outlet or channel between
      the small saphenous vein and the medial gastrocnemius veins did not increase the
      risk of deep vein thrombosis. CONCLUSION: Deep vein thrombosis after foam
      sclerotherapy of the small saphenous vein are very rare. Only 0.6% medial
      gastrocnemius veins thrombosis occurred in symptomatic patients. However, the
      anatomical pattern of the small saphenous vein should be taken into account and
      patients with medial gastrocnemius veins perforators and the small saphenous vein
      connected directly into the popliteal vein should be checked by Duplex ultrasound
      one or two weeks after the procedure. Recommendations based on our everyday
      practice and the findings of this study are suggested to prevent and treat deep
      vein thrombosis.

PMID- 23864535
TI  - The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the
      efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% compared
      with placebo for the treatment of saphenofemoral junction incompetence.
AB  - OBJECTIVE: VANISH-2 Investigator Group: K Gibson, Bellevue, WA, USA; M Goldman,
      San Diego, CA, USA; P Hertzman, Los Alamos, NM, USA; S Hirsch, Pittsburgh, PA,
      USA; R Hye, San Diego, CA, USA; M Isaacs, Walnut Creek, CA, USA; M Plaza-Ponte,
      Monroeville, PA, USA; S Rathbun, Oklahoma City, OK, USA; J Rhodes, Rochester, NY,
      USA; G Rosenberg, Frederick, MD, USA; M Schul, Lafayette, IN, USA; M Stanbro,
      Greenville, SC, USA; and R Weiss, Hunt Valley, MD, USA To determine efficacy and
      safety of polidocanol endovenous microfoam in treatment of symptoms and
      appearance in patients with saphenofemoral junction incompetence due to reflux of
      the great saphenous vein or major accessory veins. METHOD: Patients were
      randomized equally to receive polidocanol endovenous microfoam 0.5%, polidocanol
      endovenous microfoam 1.0% or placebo. The primary efficacy endpoint was patient
      reported improvement in symptoms, as measured by the change from baseline to Week
      8 in the 7-day average electronic daily diary VVSymQTM score. The co-secondary
      endpoints were the improvement in appearance of visible varicosities from
      baseline to Week 8, as measured by patients and by an independent physician
      review panel. RESULTS: In 232 treated patients, polidocanol endovenous microfoam
      0.5% and polidocanol endovenous microfoam 1.0% were superior to placebo, with a
      larger improvement in symptoms (VVSymQ (-6.01 and-5.06, respectively, versus 
      2.00; P < 0.0001) and greater improvements in physician and patient assessments
      of appearance (P < 0.0001). These findings were supported by the results of
      duplex ultrasound and other clinical measures. Of the 230 polidocanol endovenous
      microfoam-treated patients (including open-label patients), 60% had an adverse
      event compared with 39% of placebo; 95% were mild or moderate. No pulmonary
      emboli were detected and no clinically important neurologic or visual adverse
      events were reported. The most common adverse events in patients treated with
      polidocanol endovenous microfoam were retained coagulum, leg pain and superficial
      thrombophlebitis; most were related to treatment and resolved without sequelae.
      CONCLUSION: Polidocanol endovenous microfoam provided clinically meaningful
      benefit in treating symptoms and appearance in patients with varicose veins.
      Polidocanol endovenous microfoam was an effective and comprehensive minimally
      invasive treatment for patients with a broad spectrum of vein disease (clinical,
      etiology, anatomy, pathophysiology clinical class C2 to C6) and great saphenous
      vein diameters ranging from 3.1 to 19.4 mm. Treatment with polidocanol endovenous
      microfoam was associated with mild or moderate manageable side effects. VVSymQ is
      an important new, validated instrument for symptom assessment in patients with
      varicose veins.

PMID- 23864536
TI  - Healthy feeding habits: efficacy results from a cluster-randomized, controlled
      exploratory trial of a novel, habit-based intervention with parents.
AB  - BACKGROUND: As dietary gatekeepers for young children, parents are often the
      proximal target of family-based dietary interventions. Habit theory offers a
      novel approach to modifying parental feeding, based on "context-dependent
      repetition" to promote automatic responding and to reduce decisional conflict.
      OBJECTIVE: This exploratory trial evaluated an intervention promoting habit
      formation for 3 parental feeding behaviors: serving fruit/vegetables, serving
      healthy snacks, and serving nonsweetened drinks. The primary outcome was parental
      habit strength for each behavior. The secondary outcome was children's food
      intake. DESIGN: Parents of children aged 2-6 y (n = 126) were recruited from 6
      children's centers in London and cluster-randomized to intervention (n = 3) or no
      treatment control (n = 3) conditions. Parents in the intervention group (n = 58)
      received training on habit formation for 3 feeding behaviors; control
      participants (n = 68) were asked only to complete the measures. At baseline and
      after treatment, parents completed validated measures of subjective
      "automaticity" for feeding behaviors and a brief child food-frequency measure.
      Parents in the intervention group were interviewed about the program. The change
      between groups, after clustering was controlled for, was analyzed. RESULTS: For
      all parental feeding behaviors, automaticity increased more in the intervention
      group than in the control group (P < 0.01 for all). Significant intervention
      effects on children's intake of vegetables (P = 0.003), healthy snacks (P =
      0.009), and water (P = 0.032) were observed. Changes in children's food intake
      correlated with changes in parental automaticity of feeding behaviors, and
      program acceptability was high. CONCLUSIONS: A habit-based intervention
      successfully modified parental feeding behaviors, affected children's diets
      positively, and was well received by parents. Habit theory provides a promising
      new tool to support family-based obesity prevention. This trial was registered as
      ISRCTN09910187.

PMID- 23864537
TI  - The influence of early feeding practices on fruit and vegetable intake among
      preschool children in 4 European birth cohorts.
AB  - BACKGROUND: Fruit and vegetable intake in children remains below recommendations
      in many countries. The long-term effects of early parental feeding practices on
      fruit and vegetable intake are not clearly established. OBJECTIVE: The purpose of
      the current study was to examine whether early feeding practices influence later
      fruit and vegetable intake in preschool children. DESIGN: The study used data
      from 4 European cohorts: the British Avon Longitudinal Study of Parents and
      Children (ALSPAC), the French Etude des Determinants pre et postnatals de la
      sante et du developpement de l'Enfant study, the Portuguese Generation XXI Birth
      Cohort, and the Greek EuroPrevall study. Fruit and vegetable intake was assessed
      in each cohort by food-frequency questionnaire. Associations between early
      feeding practices, such as breastfeeding and timing of complementary feeding, and
      fruit and/or vegetable intake in 2-4-y-old children were tested by using logistic
      regressions, separately in each cohort, after adjustment for infant's age and sex
      and maternal age, educational level, smoking during pregnancy, and maternal fruit
      and vegetable intake. RESULTS: Large differences in early feeding practices were
      highlighted across the 4 European cohorts with longer breastfeeding duration in
      the Generation XXI Birth Cohort and earlier introduction to complementary foods
      in ALSPAC. Longer breastfeeding duration was consistently related to higher fruit
      and vegetable intake in young children, whereas the associations with age of
      introduction to fruit and vegetable intake were weaker and less consistent across
      the cohorts. Mothers' fruit and vegetable intake (available in 3 of the cohorts)
      did not substantially attenuate the relation with breastfeeding duration.
      CONCLUSION: The concordant positive association between breastfeeding duration
      and fruit and vegetable intake in different cultural contexts favors an
      independent specific effect.

PMID- 23864538
TI  - Intestinal absorption, metabolism, and excretion of (-)-epicatechin in healthy
      humans assessed by using an intestinal perfusion technique.
AB  - BACKGROUND: (-)-Epicatechin is a dietary flavonoid present in many foods that
      affects vascular function, but its action is limited by incomplete absorption,
      conjugation, and metabolism. Factors that influence this activity may be
      attributed to instability in the gastrointestinal lumen, low permeability across
      the intestinal wall, or active efflux from enterocytes and extensive conjugation.
      OBJECTIVE: With the use of a multilumen perfusion catheter, we investigated the
      jejunal absorption, systemic availability, metabolism, and intestinal, biliary,
      and urinary excretion of (-)-epicatechin in humans. DESIGN: In a single-center,
      randomized, open, controlled study in 8 healthy volunteers, 50 mg purified (-)
      epicatechin was perfused into an isolated jejunal segment together with
      antipyrine as a marker for absorption. (-)-Epicatechin and conjugates were
      measured in intestinal perfusates, bile, plasma, and urine. RESULTS: Forty-six
      percent of the dose was recovered in the perfusate either as unchanged (-)
      epicatechin (22 mg) or conjugates (0.8 mg); with stability taken into account,
      this result indicates that ~46% of the dose had apparently been absorbed. The
      conjugates were predominantly sulfates, which indicated conjugation by
      sulfotransferases followed by efflux from the enterocytes. In contrast,
      epicatechin glucuronides were dominant in plasma, bile, and urine. CONCLUSIONS:
      Almost one-half of the (-)-epicatechin is apparently absorbed in the jejunum but
      with substantial interindividual differences in the extent of absorption. The
      data suggest that the nature and substitution position of (-)-epicatechin
      conjugation are major determinants of the metabolic fate in the body, influencing
      whether the compound is effluxed into the lumen or absorbed into the blood and
      subsequently excreted.

PMID- 23864539
TI  - Comparison of 4 established DASH diet indexes: examining associations of index
      scores and colorectal cancer.
AB  - BACKGROUND: Multiple diet indexes have been developed to capture the Dietary
      Approaches to Stop Hypertension (DASH) dietary pattern and examine relations with
      health outcomes but have not been compared within the same study population to
      our knowledge. OBJECTIVE: We compared 4 established DASH indexes and examined
      associations with colorectal cancer. DESIGN: Scores were generated from a food
      frequency questionnaire in the NIH-AARP Diet and Health Study (n = 491,841).
      Separate indexes defined by Dixon (7 food groups, saturated fat, and alcohol),
      Mellen (9 nutrients), Fung (7 food groups and sodium), and Gunther (8 food
      groups) were used. HRs and 95% CIs for colorectal cancer were generated by using
      Cox proportional hazard models. RESULTS: From 1995 through 2006, 6752 incident
      colorectal cancer cases were ascertained. In men, higher scores were associated
      with reduced colorectal cancer incidence by comparing highest to lowest quintiles
      for all indexes as follows: Dixon (HR: 0.77; 95% CI: 0.69, 0.87), Mellen (HR:
      0.78; 95% CI: 0.71, 0.86), Fung (HR: 0.75; 95% CI: 0.68, 0.83), and Gunther (HR:
      0.81; 95% CI: 0.74, 0.90). Higher scores in women were inversely associated with
      colorectal cancer incidence by using methods defined by Mellen (HR: 0.79; 95% CI:
      0.68, 0.91), Fung (HR: 0.84; 95% CI: 0.73, 0.96), and Gunther (HR: 0.84; 95% CI:
      0.73.0.97) but not Dixon (HR: 1.01; 95% CI: 0.80, 1.28). CONCLUSION: The
      consistency in findings, particularly in men, suggests that all indexes capture
      an underlying construct inherent in the DASH dietary pattern, although the
      specific index used can affect results.

PMID- 23864540
TI  - Thiamine pharmacokinetics in Cambodian mothers and their breastfed infants.
AB  - BACKGROUND: Thiamine deficiency is common in parts of Asia and causes beriberi.
      Pharmacokinetics of thiamine in deficient populations are unknown. OBJECTIVE: We
      characterized thiamine pharmacokinetics in Cambodian mothers and their breastfed
      infants. DESIGN: Total plasma thiamine, whole-blood thiamine diphosphate (TDP),
      and breast milk total thiamine were measured in 16 healthy Cambodian mothers and
      their infants before and after mothers received oral thiamine hydrochloride (100
      mg for 5 d). Assays were also performed in 16 healthy American mothers. RESULTS:
      On day 1, Cambodian mothers were thiamine deficient, with median (range) total
      plasma thiamine and TDP concentrations of 2.4 nmol/L (0-4.4 nmol/L) and 58.0
      nmol/L (27-98 nmol/L), respectively. After a single oral dose, the mean +/- SD
      maximal concentration of thiamine and net area under the thiamine concentration
      time curve were 73.4 +/- 45.6 nmol/L and 465 +/- 241 h . nmol ? L-1. Day 6 median
      maternal total plasma thiamine and TDP concentrations were normal [18.6 nmol/L
      (13.4-25.3 nmol/L) and 76.5 nmol/L (48-107 nmol/L), respectively; P <= 0.001
      compared with day 1]. Median Cambodian total breast milk thiamine concentration
      increased from 180 nmol/L (85-359 nmol/L) on day 1 to 403 nmol/L (314-415 nmol/L)
      on day 2 and 503 nmol/L (360-808 nmol/L) on day 6; the corresponding American
      breast milk value was 500 nmol/L (114-622 nmol/L). Median Cambodian infant total
      plasma thiamine and TDP concentrations increased from 3.0 nmol/L (0-7.3 nmol/L)
      and 38.5 nmol/L (23-57 nmol/L), respectively, on day 1 to 5.6 nmol/L (0-9.7
      nmol/L) and 45.5 nmol/L (32-70 nmol/L), respectively, on day 6. CONCLUSIONS:
      Thiamine-deficient Cambodian mothers effectively absorb oral thiamine, with sharp
      increases in breast milk thiamine concentrations, but their breastfed infants
      remain thiamine deficient after 5 d of maternal supplementation. Longer-term
      maternal supplementation may be necessary to correct thiamine deficiency in
      breastfed infants. This trial was registered at clinicaltrials.gov as
      NCT01864057.

PMID- 23864541
TI  - The effect of age and weight on vancomycin serum trough concentrations in
      pediatric patients.
AB  - BACKGROUND: Vancomycin treatment failure has been associated with low serum
      vancomycin trough concentrations, prompting recommendations to increase the daily
      doses in adults and children. Despite more aggressive vancomycin dosing, there
      continues to be significant variability in vancomycin trough concentrations in
      pediatric patients. METHODS: To determine if vancomycin trough concentrations in
      pediatric patients differ by age and weight, we reviewed records of hospitalized
      patients who received vancomycin between 2008 and 2012. Patients were divided
      into groups that received vancomycin 40 mg/kg/day (2008-2009) or 60 mg/kg/day
      (2010-2012). Vancomycin trough concentrations were compared between groups and
      within the 60 mg/kg/day group, stratified by patient age and weight. RESULTS:
      After increasing the vancomycin dose from 40 to 60 mg/kg/day, initial trough
      concentrations increased significantly in patients younger than 2 and greater
      than 6 years of age, but not in patients between the ages of 2 and 5 years. In
      the 60 mg/kg/day group, only 16.7% of patients between 2 and 5 years of age had
      initial trough concentrations in the therapeutic range (10-20 MUg/ml). Initial
      trough concentrations were therapeutic in a greater proportion of patients ages 6
      12 years (38.7%) and 13-18 years (63.0%). Patients between the ages of 13 and 18
      had the highest proportion of supratherapeutic initial vancomycin trough
      concentrations (14.8%). Patients weighing over 50 kg had significantly higher
      trough concentrations than patients  50 kg or less (17.1 MUg/ml vs 9.3 MUg/ml,
      p<0.001). CONCLUSION: Although increasing the vancomycin dose from 40 to 60
      mg/kg/day led to a significant increase in vancomycin trough concentrations, a
      large proportion of patients receiving 60 mg/kg/day of vancomycin had trough
      concentrations outside of the therapeutic range. Specifically, patients younger
      than 6 years tended to have low trough concentrations, whereas adolescents and
      children over 50 kg were more likely to have elevated trough concentrations.
      Vancomycin dosing strategies in pediatric patients should consider age and weight
      as well as renal function and indication.

PMID- 23864542
TI  - Association between exercise and posttraumatic stress symptoms among trauma
      exposed adults.
AB  - The present investigation examined associations between intensities of exercise
      involvement and posttraumatic stress (PTS) symptom cluster severity
      (reexperiencing, avoidance/numbing, and hyperarousal). The sample was comprised
      of 108 adults (54.6% women; M age = 23.9, SD = 10.22, range = 18-62), who
      endorsed exposure to a Diagnostic and Statistical Manual of Mental Disorders
      (Fourth edition, Text Revision) posttraumatic stress disorder Criterion A
      traumatic life event but did not meet criteria for any current Axis I
      psychopathology. After controlling for gender and lifetime number of trauma
      exposure types experienced, results indicated that vigorous-intensity exercise,
      but not light- or moderate-intensity exercise, was significantly inversely
      associated with hyperarousal symptom cluster severity. This study adds to the
      scarce, yet growing, body of exercise-PTS literature-by illuminating the inverse
      associations of vigorous-intensity exercise, specifically, and PTS hyperarousal
      symptom severity among trauma-exposed individuals. 

PMID- 23864543
TI  - Subthreshold traits of the broad autistic spectrum are distributed across
      different subgroups in parents, but not siblings, of probands with autism.
AB  - Autism is a categorical developmental disorder characterized by impairment in
      socialization, communication, and by restricted and circumscribed interests.
      Several authors have described the presence of subthreshold autistic traits in
      the general population, pervasive developmental disorders representing the
      extreme end of their distribution. In this study, we explored the presence of
      autistic traits in siblings and parents of a proband with autism, and in siblings
      and parents of a normally developing child, using the previously validated self
      report French Autism Quotient, an adaptation of the AQ developed by S. Baron
      Cohen. Scores were distributed between two main factors, F1 corresponding to
      socialization and communication, F2 to imagination and rigidity. Here, we show
      that both parents and siblings of a child with autism have more symptomatic
      scores in the domains of communication and socialization. In addition, we show
      that in these families the parents, but not the siblings, are distributed across
      different subcategories, according to their scores for the F1 and F2 domains. We
      hypothesize that these different subgroups may correspond to different underlying
      genetic mechanisms. 

PMID- 23864545
TI  - Nocardiopsis sp. SD5: a potent feather degrading rare actinobacterium isolated
      from feather waste in Tamil Nadu, India.
AB  - Feather waste, generated in large quantities as a byproduct of commercial poultry
      processing, is nearly pure keratin protein, and keratin in its native state is
      not degradable by common proteolytic enzymes. The aim of the study was to find a
      potent feather degrading actinobacteria from feather waste soil. Out of 91
      actinobacterial isolates recorded from feather waste soil in Tiruchirappalli and
      Nammakkal District, Tamil Nadu, India, isolate SD5 was selected for
      characterization because it exhibited significant keratinolytic activity. On the
      basis of the phenotypic, biochemical characterization and 16S rRNA gene
      sequencing studies, the isolate was identified as Nocardiopsis sp. SD5. Protease
      and keratinase activity of Nocardiopsis sp. SD5 were analyzed. The enzyme was
      more stable over the neutral pH and the temperature of 40  degrees C. The optimum
      temperature and pH for both proteolytic and keratinolytic activity was determined
      at 50  degrees C and pH 9, respectively. Enzyme inhibitors, detergents and
      chelator declined the enzyme activity with increasing concentration.
      Nondenaturing polyacrylamide gel electrophoresis and zymogram elucidated the
      presence of 30 and 60 kDa protease enzymes. These findings indicated that thermo
      alkaliphilic feather degrading strain Nocardiopsis sp. SD5 could be used to
      control the feather waste pollution and to convert keratin rich feather waste
      into useful feedstock for poultry industry.

PMID- 23864544
TI  - Gut microbiota imbalance and chaperoning system malfunction are central to
      ulcerative colitis pathogenesis and can be counteracted with specifically
      designed probiotics: a working hypothesis.
AB  - In this work, we propose that for further studies of the physiopathology and
      treatment for inflammatory bowel diseases, an integral view of the conditions,
      including the triad of microbiota-heat shock proteins (HSPs)-probiotics, ought to
      be considered. Microbiota is the complex microbial flora that resides in the gut,
      affecting not only gut functions but also the health status of the whole body.
      Alteration in the microbiota's composition has been implicated in a variety of
      pathological conditions (e.g., ulcerative colitis, UC), involving both gut and
      extra-intestinal tissues and organs. Some of these pathologies are also
      associated with an altered expression of HSPs (chaperones) and this is the reason
      why they may be considered chaperonopathies. Probiotics, which are live
      microorganisms able to restore the correct, healthy equilibrium of microbiota
      composition, can ameliorate symptoms in patients suffering from UC and modulate
      expression levels of HSPs. However, currently probiotic therapy follows ex
      adiuvantibus criteria, i.e., treatments with beneficial effects but whose
      mechanism of action is unknown, which should be changed so the probiotics needed
      in each case are predetermined on the basis of the patient's microbiota.
      Consequently, efforts are necessary to develop diagnostic tools for elucidating
      levels and distribution of HSPs and the microbiota composition (microbiota
      fingerprint) of each subject and, thus, guide specific probiotic therapy,
      tailored to meet the needs of the patient. Microbiota fingerprinting ought to
      include molecular biology techniques for sequencing highly conserved DNA, e.g.,
      genes encoding 16S RNA, for species identification and, in addition,
      quantification of each relevant microbe. 

PMID- 23864548
TI  - RE: Hernandez, R., Blanco, S., Peragon, J., Pedrosa, J. A., & Peinado, M. A.
      (2012). Hypobaric hypoxia and reoxygenation induce proteomic profile changes in
      the rat brain cortex. Neuromolecular Medicine, doi:10.1007/s12017-012-8197-7.

PMID- 23864549
TI  - In-silico modeling of atrial repolarization in normal and atrial fibrillation
      remodeled state.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total
      number of AF patients is constantly increasing. The mechanisms leading to and
      sustaining AF are not completely understood yet. Heterogeneities in atrial
      electrophysiology seem to play an important role in this context. Although some
      heterogeneities have been used in in-silico human atrial modeling studies, they
      have not been thoroughly investigated. In this study, the original
      electrophysiological (EP) models of Courtemanche et al., Nygren et al. and
      Maleckar et al. were adjusted to reproduce action potentials in 13 atrial
      regions. The parameter sets were validated against experimental action potential
      duration data and ECG data from patients with AV block. The use of the
      heterogeneous EP model led to a more synchronized repolarization sequence in a
      variety of 3D atrial anatomical models. Combination of the heterogeneous EP model
      with a model of persistent AF-remodeled electrophysiology led to a drastic change
      in cell electrophysiology. Simulated Ta-waves were significantly shorter under
      the remodeling. The heterogeneities in cell electrophysiology explain the
      previously observed Ta-wave effects. The results mark an important step toward
      the reliable simulation of the atrial repolarization sequence, give a deeper
      understanding of the mechanism of atrial repolarization and enable further
      clinical investigations. 

PMID- 23864550
TI  - Power type strain energy function model and prediction of the anisotropic
      mechanical properties of skin using uniaxial extension data.
AB  - Many successful models to describe the biomechanical characteristics of planar
      biological soft tissues are based on strain energy function. However, the
      parameters in these models are determined by biaxial extension test, which might
      be difficult to exercise for certain types of soft tissue. This study presents a
      new constitutive model, the power type strain energy density function model
      (PTM), and a method to identify its material parameters for rabbit skin using
      uniaxial extension test of 4-direction strip samples. The abdominal skins from
      eight rabbits were taken to perform uniaxial tension tests in 7 different
      directions. The material parameters were identified for each subject based on any
      4 out of 7 directions by applying some definite conditions of this issue. For
      each rabbit, the 35 groups of material parameters were consistent. The 7 material
      parameters in PTM were identified with root mean square errors <0.061. The
      results indicate that the material parameters of rabbit skin can be identified
      from uniaxial extension test data. 

PMID- 23864551
TI  - Separation of 1,3-dimethylamylamine and other polar compounds in a dietary
      supplement formulation using aqueous normal phase chromatography with MS.
AB  - Five ingredients (caffeine, L-arginine, creatine, beta-alanine, and 1,3
      dimethylamylamine) from a workout supplement were separated by HPLC with UV
      detection and LC-MS using an analytical column based on silica hydride operating
      in aqueous normal phase mode. While RP methods were observed to be inadequate for
      the analysis due to low retention, aqueous normal phase chromatography was able
      to readily retain and resolve the analytes. After method development on the HPLC
      UV system, the conditions were successfully transferred to an LC-MS system for
      analysis. Based on calibration curve data, estimates of 63.5, 380.3, and 13.1
      mg/serving (5.50 g) were obtained for creatine, l-arginine, and 1,3
      dimethylamylamine, respectively. Standard addition data results were compared to
      those of the calibration curve study, and the two values differed by less than 1%
      in the case of creatine. The conditions are suitable for further development as a
      reliable means of quantitating the analytes in workout supplement formulations.

PMID- 23864552
TI  - Microtubule dynamics in neuronal morphogenesis.
AB  - Microtubules (MTs) are essential for neuronal morphogenesis in the developing
      brain. The MT cytoskeleton provides physical support to shape the fine structure
      of neuronal processes. MT-based motors play important roles in nucleokinesis,
      process formation and retraction. Regulation of MT stability downstream of
      extracellular cues is proposed to be critical for axonogenesis. Axons and
      dendrites exhibit different patterns of MT organization, underlying the divergent
      functions of these processes. Centrosomal positioning has drawn the attention of
      researchers because it is a major clue to understanding neuronal MT organization.
      In this review, we focus on how recent advances in live imaging have revealed the
      dynamics of MT organization and centrosome positioning during neural development.

PMID- 23864554
TI  - Mechanics of spreading cells probed by atomic force microscopy.
AB  - Cellular adhesion and motility are fundamental processes in biological systems
      such as morphogenesis and tissue homeostasis. During these processes, cells
      heavily rely on the ability to deform and supply plasma membrane from pre
      existing membrane reservoirs, allowing the cell to cope with substantial
      morphological changes. While morphological changes during single cell adhesion
      and spreading are well characterized, the accompanying alterations in cellular
      mechanics are scarcely addressed. Using the atomic force microscope, we measured
      changes in cortical and plasma membrane mechanics during the transition from
      early adhesion to a fully spread cell. During the initial adhesion step, we found
      that tremendous changes occur in cortical and membrane tension as well as in
      membrane area. Monitoring the spreading progress by means of force measurements
      over 2.5 h reveals that cortical and membrane tension become constant at the
      expense of excess membrane area. This was confirmed by fluorescence microscopy,
      which shows a rougher plasma membrane of cells in suspension compared with spread
      ones, allowing the cell to draw excess membrane from reservoirs such as
      invaginations or protrusions while attaching to the substrate and forming a first
      contact zone. Concretely, we found that cell spreading is initiated by a
      transient drop in tension, which is compensated by a decrease in excess area.
      Finally, all mechanical parameters become almost constant although morphological
      changes continue. Our study shows how a single cell responds to alterations in
      membrane tension by adjusting its overall membrane area. Interference with
      cytoskeletal integrity, membrane tension and excess surface area by
      administration of corresponding small molecular inhibitors leads to perturbations
      of the spreading process. 

PMID- 23864555
TI  - Synthesis of phosphorus-doped graphene and its multifunctional applications for
      oxygen reduction reaction and lithium ion batteries.
AB  - We develop a simple and economical thermal annealing method for the synthesis of
      phosphorus-doped graphene, which exhibits remarkable electrocatalytic activity
      towards the oxygen reduction reaction and enhances the electrochemical
      performance as an anode material for lithium ion batteries. The experimental
      results suggest the significant role of phosphorus atoms in graphene. 

PMID- 23864553
TI  - Molecular mechanisms of cell-cell spread of intracellular bacterial pathogens.
AB  - Several bacterial pathogens, including Listeria monocytogenes, Shigella flexneri
      and Rickettsia spp., have evolved mechanisms to actively spread within human
      tissues. Spreading is initiated by the pathogen-induced recruitment of host
      filamentous (F)-actin. F-actin forms a tail behind the microbe, propelling it
      through the cytoplasm. The motile pathogen then encounters the host plasma
      membrane, forming a bacterium-containing protrusion that is engulfed by an
      adjacent cell. Over the past two decades, much progress has been made in
      elucidating mechanisms of F-actin tail formation. Listeria and Shigella produce
      tails of branched actin filaments by subverting the host Arp2/3 complex. By
      contrast, Rickettsia forms tails with linear actin filaments through a bacterial
      mimic of eukaryotic formins. Compared with F-actin tail formation, mechanisms
      controlling bacterial protrusions are less well understood. However, recent
      findings have highlighted the importance of pathogen manipulation of host cell
      cell junctions in spread. Listeria produces a soluble protein that enhances
      bacterial protrusions by perturbing tight junctions. Shigella protrusions are
      engulfed through a clathrin-mediated pathway at 'tricellular junctions'-
      specialized membrane regions at the intersection of three epithelial cells. This
      review summarizes key past findings in pathogen spread, and focuses on recent
      developments in actin-based motility and the formation and internalization of
      bacterial protrusions.

PMID- 23864556
TI  - The PYL4 A194T mutant uncovers a key role of PYR1-LIKE4/PROTEIN PHOSPHATASE 2CA
      interaction for abscisic acid signaling and plant drought resistance.
AB  - Because abscisic acid (ABA) is recognized as the critical hormonal regulator of
      plant stress physiology, elucidating its signaling pathway has raised promise for
      application in agriculture, for instance through genetic engineering of ABA
      receptors. PYRABACTIN RESISTANCE1/PYR1-LIKE (PYL)/REGULATORY COMPONENTS OF ABA
      RECEPTORS ABA receptors interact with high affinity and inhibit clade A
      phosphatases type-2C (PP2Cs) in an ABA-dependent manner. We generated an allele
      library composed of 10,000 mutant clones of Arabidopsis (Arabidopsis thaliana)
      PYL4 and selected mutations that promoted ABA-independent interaction with
      PP2CA/ABA-HYPERSENSITIVE3. In vitro protein-protein interaction assays and size
      exclusion chromatography confirmed that PYL4(A194T) was able to form stable
      complexes with PP2CA in the absence of ABA, in contrast to PYL4. This interaction
      did not lead to significant inhibition of PP2CA in the absence of ABA; however,
      it improved ABA-dependent inhibition of PP2CA. As a result, 35S:PYL4(A194T)
      plants showed enhanced sensitivity to ABA-mediated inhibition of germination and
      seedling establishment compared with 35S:PYL4 plants. Additionally, at basal
      endogenous ABA levels, whole-rosette gas exchange measurements revealed reduced
      stomatal conductance and enhanced water use efficiency compared with
      nontransformed or 35S:PYL4 plants and partial up-regulation of two ABA-responsive
      genes. Finally, 35S:PYL4(A194T) plants showed enhanced drought and dehydration
      resistance compared with nontransformed or 35S:PYL4 plants. Thus, we describe a
      novel approach to enhance plant drought resistance through allele library
      generation and engineering of a PYL4 mutation that enhances interaction with
      PP2CA. 

PMID- 23864557
TI  - Enlarging cells initiating apomixis in Hieracium praealtum transition to an
      embryo sac program prior to entering mitosis.
AB  - Hieracium praealtum forms seeds asexually by apomixis. During ovule development,
      sexual reproduction initiates with megaspore mother cell entry into meiosis and
      formation of a tetrad of haploid megaspores. The sexual pathway ceases when a
      diploid aposporous initial (AI) cell differentiates, enlarges, and undergoes
      mitosis, forming an aposporous embryo sac that displaces sexual structures.
      Embryo and endosperm development in aposporous embryo sacs is fertilization
      independent. Transcriptional data relating to apomixis initiation in Hieracium
      spp. ovules is scarce and the functional identity of the AI cell relative to
      other ovule cell types is unclear. Enlarging AI cells with undivided nuclei,
      early aposporous embryo sacs containing two to four nuclei, and random groups of
      sporophytic ovule cells not undergoing these events were collected by laser
      capture microdissection. Isolated amplified messenger RNA samples were sequenced
      using the 454 pyrosequencing platform and comparatively analyzed to establish
      indicative roles of the captured cell types. Transcriptome and protein motif
      analyses showed that approximately one-half of the assembled contigs identified
      homologous sequences in Arabidopsis (Arabidopsis thaliana), of which the vast
      majority were expressed during early Arabidopsis ovule development. The
      sporophytic ovule cells were enriched in signaling functions. Gene expression
      indicative of meiosis was notably absent in enlarging AI cells, consistent with
      subsequent aposporous embryo sac formation without meiosis. The AI cell
      transcriptome was most similar to the early aposporous embryo sac transcriptome
      when comparing known functional annotations and both shared expressed genes
      involved in gametophyte development, suggesting that the enlarging AI cell is
      already transitioning to an embryo sac program prior to mitotic division. 

PMID- 23864558
TI  - The effect of chronic kisspeptin administration on seminal fructose levels in
      male mice.
AB  - The discovery that kisspeptin was critical for normal fertility in all mammalian
      species including humans, ushered in a new chapter in our understanding of the
      control of GnRH secretion. Kisspeptin, the product of the KISS1 gene, plays an
      essential role in the regulation of spermatogenesis acting primarily at the
      hypothalamic level of the gonadotropic axis. Among the many identified substances
      in human semen, fructose is becoming increasingly significant. Fructose is
      synthesized and secreted by the seminal vesicles. Its synthesis is regulated by
      androgens and it is correlated directly with the levels of testosterone. Dose
      dependent degeneration of seminal vesicle has been described following
      intraperitoneal kisspeptin treatment; however, effects of kisspeptin
      administration on the levels of seminal fructose remain elusive till date. The
      present study, therefore, addresses the effects of 12-day administration of
      kisspeptin on seminal fructose levels in male mice. Kisspeptin-10 was
      administered intraperitoneally at different dosage concentrations (1 MUg, 1 ng,
      and 10 rhog) to adult male mice, twice daily for 12 days. Seminal fructose levels
      were studied photometrically after 12 days of treatment. At the end of the
      treatment, seminal fructose levels decreased significantly after all tested
      doses. Chronic intermittent kisspeptin-10 administration negatively regulates
      seminal fructose levels in adult male mice.

PMID- 23864559
TI  - Experience with plerixafor for hematopoietic cell mobilization in nine patients
      with germ cell tumors.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of plerixafor as a just-in-time therapy
      for patients with germ cell tumors who were identified as poor hematopoietic cell
      mobilizers after the initiation of apheresis. DESIGN: Case series. SETTING:
      National Cancer Institute-designated cancer center. PATIENTS: Nine patients with
      germ cell tumors who received plerixafor as an adjunct to granulocyte colony
      stimulating factor (G-CSF) for hematopoietic cell mobilization in an attempt to
      prevent mobilization failure between January 2009 and December 2012. MEASUREMENTS
      AND MAIN RESULTS: Patients were heavily pretreated, having received at least four
      prior treatment cycles. A median of three total apheresis days (range 1-4 days)
      was required for all patients, but a median of two apheresis days (range 1-2
      days) was needed after the initiation of plerixafor. A median of 0.9 * 106 CD34+
      cells/kg (range 0.3-1.5 * 106 CD34+ cells/kg) was harvested with G-CSF
      mobilization alone; in addition, a median of 2.6 * 106 CD34+ cells/kg (range 0.6
      32 * 106 CD34+ cells/kg) was harvested using plerixafor. All nine patients
      received high-dose carboplatin and etoposide followed by hematopoietic cell
      transplantation. The median time to neutrophil engraftment was 11 days (range 8
      12 days). The median time to platelet engraftment was 16 days (range 10-22 days).
      CONCLUSIONS: The use of plerixafor in addition to G-CSF as just-in-time therapy
      permits patients with germ cell tumors to pursue potentially curative therapy
      with high-dose chemotherapy followed by autologous stem cell rescue.

PMID- 23864560
TI  - Reply to "comment on high-efficiency panchromatic hybrid Schottky solar cells".

PMID- 23864561
TI  - Association of rhizobia with a marine polychaete.
AB  - We report the presence of Mesorhizobium, a genus best known for its nitrogen
      fixing symbiosis with terrestrial legumes, associated with the marine polychaete
      Meganerilla bactericola (Annelida: Nerillidae). Abundant epibionts were
      previously described as coating the exterior of M. bactericola, which is found
      within the anoxic sulfide-oxidizing microbial mats of the Santa Barbara Basin,
      California, USA. 16S rRNA investigation of the bacterial community associated
      with this polychaete discovered the presence of bacteria belonging to
      Mesorhizobium. We identified these bacteria using phylogenetic analyses of 16S
      rRNA and three additional functional genes, nifH, atpD and recA, and group
      specific fluorescence in situ hybridization (FISH). 

PMID- 23864562
TI  - Localization and morphological variation of three bacteriome-inhabiting symbionts
      within a planthopper of the genus Oliarus (Hemiptera: Cixiidae).
AB  - Many planthoppers of the family Cixiidae (Hemiptera: Fulgoroidea) host three
      bacteriome-inhabiting bacteria: a gammaproteobacterium: 'Ca.Purcelliella
      pentastirinorum', a betaproteobacterium: 'Ca. Vidania fulgoroidea', and a member
      of the bacteroidetes: 'Ca.Sulcia muelleri'. Through light microscopy
      observations, DGGE PCR and FISH analysis, we examined the morphology and
      localization of these three endosymbionts within the abdomens of females of the
      planthopper Oliarus filicicola. Our results indicate a complex distribution and
      variation in bacterial morphologies. 'Ca. Sulcia muelleri' singularly colonize
      one pair of bacteriomes and have cells of irregular shape with an average
      diameter of approximately 4-5 MUm. 'Ca.Purcelliella pentastirinorum' bacteria are
      roughly globular and have an average diameter of approximately 1.5-2 MUm in a
      pair of bacteriomes located near the posterior end of the abdomen, which are
      surrounded by giant and highly degenerated cells of 'Ca.Vidania fulgoroidea'. In
      addition, 'Ca.Vidania fulgoroidea' colonizes the 'rectal organ' (sensu Buchner)
      and the bacterial cells appear as a small, roughly globular with an average
      diameter of 3 MUm; whereas, 'Ca.Purcelliella pentastirinorum' infects an
      additional two bacteriomes and the bacterial cells appear tightly packed and
      highly degenerated. All three endosymbionts colocalize in the forming eggs inside
      the host's ovaries. Based on the abdominal distribution of bacteriomes and
      bacterial morphologies, we suggest that 'Ca.Vidania fulgoroidea' and
      'Ca.Purcelliella pentastirinorum' correspond to the symbionts described by
      Buchner as the 'x-' and the 'c + d symbiont' respectively.

PMID- 23864563
TI  - Do the honeybee pathogens Nosema ceranae and deformed wing virus act
      synergistically?
AB  - The honeybee pathogens Nosema ceranae and deformed wing virus (DWV) cause the
      collapse of honeybee colonies. Therefore, it is plausible that these two
      pathogens act synergistically to increase colony losses, since N.ceranae causes
      damage to the mid-gut epithelial ventricular cells and actively suppresses the
      honeybees' immune response, either of which could increase the virulence of viral
      pathogens within the bee. To test this hypothesis we exploited 322 Hawaiian
      honeybee colonies for which DWV prevalence and load is known. We determined via
      PCR that N.ceranae was present in 89-95% of these colonies, with no Nosema apis
      being detected. We found no significant difference in spore counts in colonies
      infected with DWV and those in which DWV was not detected, either on any of the
      four islands or across the entire honeybee population. Furthermore, no
      significant correlation between DWV loads (DeltaCT levels) and N.ceranae spore
      counts was found, so these two pathogens are not acting synergistically. Although
      the Hawaiian honeybees have the highest known prevalence of N.ceranae in the
      world, with average number of spores been 2.7 million per bee, no acute Nosema
      related problems i.e. large-scale colony deaths, have been reported by Hawaiian
      beekeepers.

PMID- 23864564
TI  - Autophagy is required for trap formation in the nematode-trapping fungus
      Arthrobotrys oligospora.
AB  - Nematode-trapping fungi live mainly as saprobes in soil environments. When
      encountering nematodes, these fungi become 'carnivorous' and develop specialized
      trapping devices to attack their hosts for extracting nutrients, especially
      nitrogen source. Thus, nematode-trapping fungi are model organisms for
      understanding the molecular mechanism of the switch between saprobic and
      parasitic phases of pathogen life cycles. Arthrobotrys oligospora, one of the
      best-studied nematode-trapping fungi, mainly lives as a saprobe. In the presence
      of nematodes, A.oligospora enters the parasitic stage by forming adhesive
      reticulate traps to capture nematodes. In filamentous fungi, autophagy has been
      shown to be involved in morphogenesis and morphology. In this study, we
      demonstrate that autophagy is induced by nematodes during the early stage of trap
      formation in A.oligospora. Disruption of atg8 gene not only abolishes the
      nematode-induced autophagy, but also suppresses trap formation and reduces
      pathogenicity for nematodes. During the early stage of trap formation, the
      expression of genes involved in amino acid biosynthesis is upregulated and the
      transcriptional activity of GCN4 is induced in A.oligospora, suggesting that
      nematodes induce autophagy probably by triggering intracellular amino acid
      starvation. Autophagy is thus crucial for trap formation in A.oligospora during
      infection of nematodes.

PMID- 23864565
TI  - Sulfur-oxidizing bacterial populations within cyanobacterial dominated coral
      disease lesions.
AB  - This study investigated the diversity and quantitative shifts of sulfur-oxidizing
      bacteria (SOB) during the onset of black band disease (BBD) in corals using
      quantitative PCR (qPCR) and cloning approaches targeting the soxB gene, involved
      in sulfur oxidation. Four Montipora sp. coral colonies identified with lesions
      previously termed cyanobacterial patches (CP) (comprising microbial communities
      different from those of BBD lesions), was monitored in situ as CP developed into
      BBD. The overall abundance of SOB in both CP and BBD lesions were very low and
      near the detection limit of the qPCR assay, although consistently indicated that
      SOB populations decreased as the lesions transitioned from CP to BBD.
      Phylogenetic assessment of retrieved soxB genes showed that SOB in both CP and
      BBD lesions were dominated by one sequence type, representing > 70% of all soxB
      gene sequences and affiliated with members of the Rhodobacteraceae within the
      alpha-Proteobacteria. This study represents the first assessment targeting SOB
      within BBD lesions and clearly shows that SOB are not highly diverse or abundant
      in this complex microbial mat. The lack of oxidation of reduced sulfur compounds
      by SOB likely aids the accumulation of high levels of sulfide at the base of the
      BBD mat, a compound contributing to the pathogenicity of BBD lesions.

PMID- 23864566
TI  - A typing scheme for the honeybee pathogen Melissococcus plutonius allows
      detection of disease transmission events and a study of the distribution of
      variants.
AB  - Melissococcus plutonius is the bacterial pathogen that causes European Foulbrood
      of honeybees, a globally important honeybee brood disease. We have used next
      generation sequencing to identify highly polymorphic regions in an otherwise
      genetically homogenous organism, and used these loci to create a modified MLST
      scheme. This synthesis of a proven typing scheme format with next-generation
      sequencing combines reliability and low costs with insights only available from
      high-throughput sequencing technologies. Using this scheme we show that the
      global distribution of M.plutonius variants is not uniform. We use the scheme in
      epidemiological studies to trace movements of infective material around England,
      insights that would have been impossible to confirm without the typing scheme. We
      also demonstrate the persistence of local variants over time.

PMID- 23864568
TI  - Live feed is not a major determinant of the microbiota associated with cod larvae
      (Gadus morhua).
AB  - The gastrointestinal (GI) tract of newly hatched fish is probably colonized by
      bacteria present in the water, but how environmental and internal factors affect
      the development of the GI microbiota is poorly understood. In this study, we
      investigated the effect of diet and of rearing in separate tanks on the cod
      larval microbiota. Cod larvae were fed three different live feed diets. For each
      diet, larvae were reared in three replicate tanks. The microbial communities were
      investigated for water, live feed and individual larvae using a PCR/DGGE
      (Denaturing Gradient Gel Electrophoresis) strategy. Statistical tests were
      applied to investigate differences in the larval microbiota between groups of
      individuals. We found no differences in the larval microbiota due to diet after 8
      dph (days post hatching). Moreover, the larval microbiota was similar at 17 and
      32 dph, despite a change in live feed at 18 dph. The larval microbiota was
      generally more similar to the water microbiota than to live feed microbiota. We
      further found that rearing of larvae in replicate tanks with identical diet could
      result in significant differences in larval microbiota. These findings indicate
      that diet does not entail major changes to the composition of cod larval
      microbiota.

PMID- 23864567
TI  - Apoptosis in the pathogenesis of Nosema ceranae (Microsporidia: Nosematidae) in
      honey bees (Apis mellifera).
AB  - Nosema ceranae is a parasite of the epithelial ventricular cells of the honey bee
      that belongs to the microsporidian phylum, a biological group of single-cell,
      spore-forming obligate intracellular parasites found in all major animal
      lineages. The ability of host cells to accommodate a large parasitic burden for
      several days suggests that these parasites subvert the normal host cells to
      ensure optimal environmental conditions for growth and development. Once
      infected, cells can counteract the invasive pathogen by initiating their own
      death by apoptosis as a defence strategy. To determine whether N. ceranae blocks
      apoptosis in infected ventricular cells, cell death was assessed in sections of
      the ventriculum from experimentally infected honey bees using the TUNEL assay and
      by immunohistochemistry for caspase-3. Ventricular epithelial cells from infected
      bees were larger than those in the uninfected control bees, and they contained N.
      ceranae at both mature and immature stages in the cytoplasm. Apoptotic nuclei
      were only observed in some restricted areas of the ventriculum, whereas apoptosis
      was typically observed throughout the epithelium in uninfected bees. Indeed, the
      apoptotic index was higher in uninfected versus infected ventriculi. Our results
      suggested that N. ceranae prevents apoptosis in epithelial cells of infected
      ventriculi, a mechanism possible designed to enhance parasite development.

PMID- 23864569
TI  - Depth-discrete profiles of bacterial communities reveal pronounced spatio
      temporal dynamics related to lake stratification.
AB  - With this work we intend to stress the importance of considering discrete depth
      sampling for bacterial community analysis of stratified aquatic systems. Depth is
      a very important parameter to consider when sampling bacterial communities, as
      their abundance and composition can change within the distinct water layers.
      Stratified lakes are good model systems to study these connections since changes
      in environmental parameters can occur on a cm-scale at the thermo- and/or
      chemocline. Lake Grosse Fuchskuhle was sampled at discrete fine-scale depths at
      three time points covering a stage in which the lake was stratified and the
      beginning of winter mixing. In this paper we present the most abundant bacterial
      groups at the different depths sampled and also the most abundant operational
      taxonomic units (OTUs). Overall, oxygen was found to be an important factor
      shaping the microbial community composition. 

PMID- 23864570
TI  - Genetic dissection of a motility-associated c-di-GMP signalling protein of
      Pseudomonas putida.
AB  - Lack of the Pseudomonas putida PP2258 protein or its overexpression results in
      defective motility on solid media. The PP2258 protein is tripartite, possessing a
      PAS domain linked to two domains associated with turnover of c-di-GMP - a cyclic
      nucleotide that controls the switch between motile and sessile lifestyles. The
      second messenger c-di-GMP is produced by diguanylate cyclases and degraded by
      phosphodiesterases containing GGDEF and EAL or HD-GYP domains respectively. It is
      common for enzymes involved in c-di-GMP signalling to contain two domains with
      potentially opposing c-di-GMP turnover activities; however, usually one is
      degenerate and has been adopted to serve regulatory functions. Only a few
      proteins have previously been found to have dual enzymatic activities - being
      capable of both synthesizing and hydrolysing c-di-GMP. Here, using truncated and
      mutant derivatives of PP2258, we show that despite a lack of complete consensus
      in either the GGDEF or EAL motifs, the two c-di-GMP turnover domains can function
      independently of each other, and that the diguanylate cyclase activity is
      regulated by an inhibitory I-site within its GGDEF domain. Thus, motility
      associated PP2258 can be added to the short list of bifunctional c-di-GMP
      signalling proteins.

PMID- 23864571
TI  - Aerobic methanotroph diversity in Riganqiao peatlands on the Qinghai-Tibetan
      Plateau.
AB  - The Zoige Plateau is characterized by its high altitude, low latitude and low
      annual mean temperature of approximately 1 degrees C and is a major source of
      atmospheric methane in the Qinghai-Tibetan Plateau. Methanotrophs play an
      important role in the global cycling of CH4, but the diversity, identity and
      activity of methanotrophs in this region are poorly characterized. Soils were
      collected from hummocks and hollows in the Riganqiao peatland and the
      methanotroph community was analysed by qPCR and sequencing methane monooxygenase
      (pmoA and mmoX) genes. The pmoA genes ranged between 10(7) and 10(8) copies g(-1)
      fresh soil, with a somewhat greater abundance in hummocks than hollows. The pmoA
      genes were analysed by amplicon pyrosequencing and the mmoX genes by cloning and
      sequencing. Methylocystis species were found to be the most abundant
      methanotrophs, but numerous clades were present including three novel pmoA and
      three novel mmoX clusters. There were differences between the methanotroph
      communities in the hummocks and hollows, with the most significant being an
      increased abundance of uncultivated type Ib methanotrophs in the hollows. The
      results indicate that aerobic methanotrophs are abundant in Riganqiao peatland
      and include previously undetected clades in this geographically isolated and
      distinctive environment.

PMID- 23864572
TI  - Selective occurrence of Rhizobiales in frost flowers on the surface of young sea
      ice near Barrow, Alaska and distribution in the polar marine rare biosphere.
AB  - Frost flowers are highly saline ice structures that grow on the surface of young
      sea ice, a spatially extensive environment of increasing importance in the Arctic
      Ocean. In a previous study, we reported organic components of frost flowers in
      the form of elevated levels of bacteria and exopolymers relative to underlying
      ice. Here, DNA was extracted from frost flowers and young sea ice, collected in
      springtime from a frozen lead offshore of Barrow, Alaska, to identify bacteria in
      these understudied environments. Evaluation of the distribution of 16S rRNA genes
      via four methods (microarray analysis, T-RFLP, clone library and shotgun
      metagenomic sequencing) indicated distinctive bacterial assemblages between the
      two environments, with frost flowers appearing to select for Rhizobiales. A
      phylogenetic placement approach, used to evaluate the distribution of similar
      Rhizobiales sequences in other polar marine studies, indicated that some of the
      observed strains represent widely distributed members of the marine rare
      biosphere in both the Arctic and Antarctic. 

PMID- 23864573
TI  - Salt deliquescence drives photosynthesis in the hyperarid Atacama Desert.
AB  - Endolithic cyanobacteria are found in halite nodules in the hyperarid core of the
      Atacama Desert. Using Pulse Amplitude Modulated Fluorometry, we show here that
      photosynthetic systems of these cyanobacteria become active when the relative
      humidity rises above 70% and the salt becomes wet by way of deliquescence. This
      is the first evidence of active metabolism in the hyperarid core of the Atacama,
      and supports the view of a microbial community sustained by deliquescence. Our
      results expand the water activity envelope of life on Earth. 

PMID- 23864574
TI  - Impact of microbial diversity depletion on xenobiotic degradation by sewage
      activated sludge.
AB  - Microbial diversity is generally considered as having no effect on the major
      processes of the ecosystem such as respiration or nutrient assimilation. However,
      information about the impact of diversity on minor functions such as xenobiotic
      degradation is scant. We studied the role of diversity on the capacity of an
      activated-sludge microbial community to eliminate phenanthrene, a polycyclic
      aromatic hydrocarbon. We also assessed the impact of diversity erosion on the
      ability of activated sludge to oxidize a wide range of organic compounds. The
      diversity of activated sludge was artificially modified by dilution to extinction
      followed by regrowth stage which led to communities with similar biomass but
      displaying a diversity gradient. The capacity of activated-sludge community to
      degrade phenanthrene was greatly modified: at high levels of diversity, the
      community was able to mineralize phenanthrene whereas at medium levels it first
      of all partially lost its ability to mineralize this pollutant and at the lowest
      diversity, the activated sludge completely lost its capacity to transform
      phenanthrene. Diversity depletion also reduced the metabolic diversity and
      biomass productivity of sewage-activated sludge. This study demonstrates that
      diversity erosion can greatly affect major ecosystem services such as pollutant
      removal. 

PMID- 23864575
TI  - Arabinogalactan and fructo-oligosaccharides have a different fermentation profile
      in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME (r)).
AB  - Current prebiotics, such as fructo-oligosaccharides (FOS), are limited in their
      persistence in the distal colon and are predominantly fermented in the proximal
      colon. In order to identify a potential alternative, the differences in the
      fermentation profile of arabinogalactan (AG) and FOS have been assessed in the
      Simulator of the Human Intestinal Microbial Ecosystem. The effect of each product
      on the composition and activity of the microbial community was analysed during a
      3-week treatment period at a dose of 5 g day(-1). While FOS indeed was mainly
      fermented in the simulated proximal colon, AG was still available for
      fermentation in the simulated distal colon as shown by pH profiles, size
      exclusion chromatography and analyses of specific enzymatic activities. As a
      consequence, the main effect of the products (increase in propionate and butyrate
      and decrease in ammonium production) occurred in different intestinal areas. DGGE
      and qPCR analyses confirmed that the main modulation of the microbiota by the two
      products occurred in different areas of the gut. AG was associated with a
      statistically significant increase in the concentration of total bacteria,
      Bacteroidetes, Faecalibacterium prausnitzii, a delayed bifidogenic effect and a
      decrease of the pathogenic Clostridium perfringens. FOS led to a strong
      lactobacillogenic effect.

PMID- 23864576
TI  - Blackbirds Turdus merula as competent reservoirs for Borrelia turdi and Borrelia
      valaisiana in Portugal: evidence from a xenodiagnostic experiment.
AB  - To confirm that thrushes, such as blackbirds Turdus merula, play a role as
      reservoir for some Borrelia genospecies, we performed a xenodiagnostic experiment
      with blackbirds captured in a mixed wood located in Western Portugal where
      Borrelia turdi, an uncommon genospecies in Europe, was the most prevalent
      genospecies associated with birds. Two out of five birds harboured B. turdi
      infected Ixodes frontalis at the time of capture. Four out of five birds
      transmitted spirochaetes to Ixodes ricinus xenodiagnostic ticks: two birds
      transmitted Borrelia valaisiana to 25.7% and 10.5% of ticks, and two transmitted
      B. turdi to 6.4% and 5.4% of ticks. Our results showed that blackbirds transmit
      B. valaisiana and B. turdi to I. ricinus feeding larvae, acting as reservoir
      hosts for these genospecies in nature.

PMID- 23864577
TI  - The Gac regulon of Pseudomonas fluorescens SBW25.
AB  - Transcriptome analysis of Pseudomonas fluorescens SBW25 showed that 702 genes
      were differentially regulated in a gacS::Tn5 mutant, with 300 and 402 genes up-
      and downregulated respectively. Similar to the Gac regulon of other Pseudomonas
      species, genes involved in motility, biofilm formation, siderophore biosynthesis
      and oxidative stress were differentially regulated in the gacS mutant of SBW25.
      Our analysis also revealed, for the first time, that transcription of 19
      rhizosphere-induced genes and of genes involved in type II secretion,
      (exo)polysaccharide and pectate lyase biosynthesis, twitching motility and an
      orphan non-ribosomal peptide synthetase (NRPS) were significantly affected in the
      gacS mutant. Furthermore, the gacS mutant inhibited growth of oomycete, fungal
      and bacterial pathogens significantly more than wild type SBW25. Since RP-HPLC
      analysis did not reveal any potential candidate metabolites, we focused on the
      Gac-regulated orphan NRPS gene cluster that was predicted to encode an eight
      amino-acid ornicorrugatin-like peptide. Site-directed mutagenesis indicated that
      the encoded peptide is not involved in the enhanced antimicrobial activity of the
      gacS mutant but may function as a siderophore. Collectively, this genome-wide
      analysis revealed that a mutation in the GacS/A two-component regulatory system
      causes major transcriptional changes in SBW25 and significantly enhances its
      antimicrobial activities by yet unknown mechanisms.

PMID- 23864578
TI  - Bacteria and the transition metals: an annotated selection of World Wide Web
      sites relevant to the topics in Environmental microbiology.

PMID- 23864579
TI  - Surgical double valve replacement after transcatheter aortic valve implantation
      and interventional mitral valve repair.
AB  - Transcatheter aortic valve implantation, as well as interventional mitral valve
      repair, offer reasonable therapeutic options for high-risk surgical patients. We
      report a rare case of early post-interventional aortic valve prosthesis migration
      to the left ventricular outflow tract, with paravalvular leakage and causing
      severe mitral valve regurgitation. Initial successful interventional mitral valve
      repair using a clipped edge-to-edge technique revealed, in a subsequent
      procedure, the recurrence of mitral valve regurgitation leading to progressive
      heart failure and necessitating subsequent surgical aortic and mitral valve
      replacement. 

PMID- 23864580
TI  - Predictive factors for complications of anatomical pulmonary segmentectomies.
AB  - OBJECTIVES: The role of anatomical pulmonary segmentectomy is increasing, but
      there are few data about its complication rate. We have analysed the
      postoperative morbidity, mortality and risk factors in a consecutive series of
      228 segmentectomies performed in our department. METHODS: Between January 2007
      and December 2011, 221 patients underwent 228 segmentectomies. There were 99
      women (45%) and 122 men (55%). The mean age was 61 years (range 18-86 years). The
      mean forced expiratory volume in 1 s (FEV1) was 87%, and 30 patients had an FEV1
      of <=60%. Fifty-seven patients had a previous history of pulmonary resection.
      Indications for segmentectomy were: primary lung cancer (111 cases), metastases
      (71 cases), benign non-infectious (25 cases) and benign infectious diseases (21
      cases). The approach was a posterolateral thoracotomy (Group PLT) in 146 patients
      (64%) and a thoracoscopy (Group TS) in 82 (36%). The two groups were homogenous
      in terms of age, gender, indications of surgery and type of segmentectomy.
      RESULTS: The mortality rate at 3 months was 1.3% (3 patients). The overall
      complication rate was 34%. Ten patients were reoperated for the following
      reasons: haemothorax (4 cases), ischaemia of the remaining segment (3 cases),
      active bleeding (1 case), prolonged air leak (1 case) and dehiscence of
      thoracotomy (1 case). The average duration of drainage was 5 days (range 1-34
      days) and the average length of stay was 9 days (range 3-126 days). On univariate
      analysis, FEV1, male gender and thoracotomy were statistically significant risk
      factors for complications. On multivariate analysis, the same three predictive
      factors of complications independently of age were found statistically
      significant: preoperative FEV1 < 60% [odds ratio (OR) = 5.9, 95% CI (2.5-13.7), P
      < 0.001] male gender [OR = 2.04, 95% CI (1.2-3.6), P < 0.013] and thoracotomy [OR
      = 2.14, 95% CI (1.33-3.46), P = 0.001]. CONCLUSIONS: Pulmonary anatomical
      segmentectomies have an acceptable morbidity rate. Postoperative complications
      are more likely to develop in male gender patients, with FEV1 <= 60% and operated
      by open surgery.

PMID- 23864581
TI  - Effects of metformin dose on cancer risk reduction in patients with type 2
      diabetes mellitus: a 6-year follow-up study.
AB  - STUDY OBJECTIVE: To explore the effects of metformin dose on cancer risk
      reduction in patients with type 2 diabetes. DESIGN: Population-based cohort
      study. DATA SOURCE: National Health Insurance program Longitudinal Health
      Insurance Database. PATIENTS: A total of 65,754 age- and gender-matched patients
      without diabetes and no previous cancer diagnosis were extracted from the
      database. MEASUREMENTS AND MAIN RESULTS: We compared cancer risk among the
      subjects who had no diabetes, had type 2 diabetes but were not on diabetes drugs,
      used metformin only, used antidiabetic drugs other than metformin, or used
      metformin in combination with other antidiabetic drugs. Our results revealed dose
      dependent effects of metformin on cancer risk and cancer onset times. A
      significant decrease in cancer risk was found in the monotherapy group who
      received more than 360 defined daily doses (DDDs) of metformin (hazard ratio [HR]
      0.40, 95% confidence interval [CI] 0.24-0.66). The greatest decrease in cancer
      risk was observed in patients who took more than 1080 DDDs (HR 0.27, 95% CI 0.09
      0.84). Significantly greater dose-dependent effects were seen in patients who
      used metformin in combination with other antidiabetic drugs. CONCLUSION: The
      magnitude of cancer risk reduction and prolonged cancer onset times produced by
      metformin in patients with type 2 diabetes depended on the dose of metformin,
      regardless of whether metformin was used alone or combined with other
      antidiabetic drugs.

PMID- 23864583
TI  - Association of race consciousness with the patient-physician relationship,
      medication adherence, and blood pressure in urban primary care patients.
AB  - BACKGROUND: Race consciousness (the frequency with which one thinks about his or
      her own race) is a measure that may be useful in assessing whether racial
      discrimination negatively impacts blood pressure (BP). However, the relation
      between race consciousness and BP has yet to be empirically tested, especially
      within the context of the patient-physician relationship and medication
      adherence. METHODS: Race-stratified generalized estimating equations were used to
      assess the relationship of race consciousness on BP, measures of the patient
      physician relationship, and self-reported medication adherence, controlling for
      patients being nested within physicians and for patient age and sex. RESULTS: The
      mean age of the patients was 61.3 years, 62% were black, and 65% were women.
      Black patients were more likely to ever think about race than were white patients
      (49% vs. 21%; P < 0.001). Race-conscious blacks had significantly higher
      diastolic BP (79.4 vs. 74.5 mm Hg; P = 0.004) and somewhat higher systolic BP
      (138.8 vs. 134.7 mm Hg; P = 0.13) than blacks who were not race conscious. Race
      conscious whites were more likely to perceive respect from their physician (57.1%
      vs. 25.8%; P = 0.01) but had lower medication adherence (62.4% vs. 82.9%; P =
      0.05) than whites who were not race-conscious. CONCLUSIONS: Among blacks, race
      consciousness was associated with higher diastolic BP. In contrast, among whites,
      there was no association between race consciousness and BP, but race
      consciousness was associated with poor ratings of adherence, despite more
      favorable ratings of the patient-physician relationship. Future work should
      explore disparities in race consciousness and its impact on health and health
      care disparities.

PMID- 23864584
TI  - Is the association of diabetes with uncontrolled blood pressure stronger in
      Mexican Americans and blacks than in whites among diagnosed hypertensive
      patients?
AB  - BACKGROUND: Clinical evidence shows that diabetes may provoke uncontrolled blood
      pressure (BP) in hypertensive patients. However, racial differences in the
      associations of diabetes with uncontrolled BP outcomes among diagnosed
      hypertensive patients have not been evaluated. METHODS: A total of 6,134
      diagnosed hypertensive subjects aged >= 20 years were collected from the National
      Health and Nutrition Examination Survey 1999-2008 with a stratified multistage
      design. Odds ratios (ORs) and relative ORs of uncontrolled BP and effect
      differences in continuous BP for diabetes over race/ethnicity were derived using
      weighted logistic regression and linear regression models. RESULTS: Compared with
      participants who did not have diabetes, non-Hispanic black participants with
      diabetes had a 138% higher chance of having uncontrolled BP, Mexican participants
      with diabetes had a 60% higher chance of having uncontrolled BP, and non-Hispanic
      white participants with diabetes had a 161% higher chances of having uncontrolled
      BP. The association of diabetes with uncontrolled BP was lower in Mexican
      Americans than in non-Hispanic blacks and whites (Mexican Americans vs. non
      Hispanic blacks: relative OR = 0.55, 95% confidence interval (CI) = 0.37-0.82;
      Mexican Americans vs. non-Hispanic whites: relative OR = 0.53, 95% CI = 0.35
      0.80) and the association of diabetes with isolated uncontrolled systolic BP was
      lower in Mexican Americans than in non-Hispanic whites (Mexican Americans vs. non
      Hispanic whites: relative OR = 0.62, 95% CI = 0.40-0.96). Mexican Americans have
      a stronger association of diabetes with decreased systolic BP and diastolic BP
      than non-Hispanic whites, and a stronger association of diabetes with decreased
      diastolic BP than non-Hispanic blacks. CONCLUSIONS: The association of diabetes
      with uncontrolled BP outcomes is lower despite higher prevalence of diabetes in
      Mexican Americans than in non-Hispanic whites. The stronger association of
      diabetes with BP outcomes in whites should be of clinical concern, considering
      they account for the majority of the hypertensive population in the United
      States.

PMID- 23864582
TI  - Disturbed sleep and inflammatory cytokines in depressed and nondepressed pregnant
      women: an exploratory analysis of pregnancy outcomes.
AB  - OBJECTIVE: Disturbed sleep and depression are potential risk factors for
      pregnancy complications. Both conditions are known to dysregulate biological
      pathways responsible for maintaining homeostatic balance and pregnancy health.
      Depression during pregnancy is associated with poor sleep. Thus, we explored
      whether disturbed sleep was associated with inflammatory cytokines and risk for
      adverse pregnancy outcomes, as well as whether depression augmented the sleep
      cytokine relationship, thereby additively contributing to risk for adverse
      outcomes. METHODS: Interview-assessed sleep and plasma cytokine concentrations
      were evaluated in a cohort of depressed and nondepressed pregnant women (n = 168)
      at 20 and 30 weeks' gestation. Outcomes evaluated included preterm birth, birth
      weight, and peripartum events. RESULTS: Among depressed women, short sleep
      duration (<7 hours) was associated with higher interleukin (IL)-8 across time
      (beta = 0.506, p = .001), poor sleep efficiency (<85%) was associated with higher
      IL-6 (beta = 0.205, p = .006), and daytime naps were associated with higher tumor
      necrosis factor alpha (beta = 0.105, p = .024). Aspects of poor sleep were
      associated with having a lower weight baby (p values <.053). Among depressed
      women, interferon-gamma increased risk for preterm birth (odds ratio = 1.175, p =
      .032). Trends for IL-6 and higher birth weight (beta = 105.2, p = .085),
      interferon-gamma and lower birth weight (beta = -19.92, p < .069), and increased
      IL-8 and babies weighing less than 4000 grams (odds ratio = 0.72, p < .083) were
      observed. CONCLUSIONS: Although speculative, disturbed sleep may disrupt normal
      immune processes and contribute to adverse pregnancy outcomes. Exploratory
      analyses indicate that depression modifies these relationships.

PMID- 23864585
TI  - Correlations of DDAH1 transcript variants with human endothelial asymmetric
      dimethylarginine metabolizing activity.
AB  - BACKGROUND: Dimethylarginine dimethylaminohydrolases 1 (DDAH1) is the major
      enzyme responsible for inactivation of asymmetric dimethylarginine (ADMA). This
      study seeks to clarify the correlations between mRNA expression levels of DDAH1
      transcript variants and the relationship with ADMA metabolizing activity in
      human. METHODS: The mRNA expression levels of DDAH1 transcript variants in
      primarily cultured human umbilical vein endothelial cells (HUVECs) and peripheral
      blood mononuclear cells (PBMCs) from healthy control subjects and patients
      suffering from both acute ischemic stroke (AIS) and acute myocardial infarction
      (AMI) were determined by real-time polymerase chain reaction. ADMA metabolizing
      activity of the cell lysates from HUVECs was determined by enzyme-linked
      immunosorbent assay. RESULTS: A novel DDAH1 transcript variant DDAH1-V3 was
      identified. DDAH1-V3 mRNA expression correlated significantly with that of both 
      V2 (R = 0.811; P = 0.000008) and -V1 (R = 0.454; P = 0.04) in HUVECs. In PBMCs
      from healthy subjects, significant correlation was observed only between DDAH1-V2
      and -V3 (R = 0.571; P = 0.001; n = 36). Delta threshold cycle (DCT) values for
      both DDAH1-V2 and -V3 transcripts were increased significantly in PBMCs from AIS
      patients (P < 0.05, respectively). In PBMCs from patients suffering from both AIS
      and AMI, positive pairwise correlations between mRNA levels of DDAH1 transcripts
      were also observed as analyzed by partial correlation analysis (P < 0.05,
      respectively). However, only mRNA expression level of the DDAH1-V1 transcript
      correlated significantly with intracellular ADMA metabolizing activity in HUVECs
      (R = 0.805; P=0.002). CONCLUSIONS: This study demonstrated that although there
      are positive correlations between mRNA expression levels of DDAH1 transcript
      variants, only the DDAH1-V1 transcript is responsible for ADMA metabolism, and
      transcript specific primers are recommended to determine DDAH1 mRNA expression.

PMID- 23864586
TI  - Relationship between augmentation index and left ventricular diastolic function
      in healthy women and men.
AB  - BACKGROUND: The aim of this study was to investigate the effect of sex on the
      correlation between arterial stiffness and left ventricular (LV) diastolic
      function in a healthy population without significant atherosclerosis. METHODS:
      Subjects (n = 446) who had simultaneous echocardiography and arterial stiffness
      recordings were enrolled. From these subjects, 95 men and 72 age-matched women
      without atherosclerotic risk factors (hypertension, dyslipidemia, and diabetes
      mellitus) were included in the analysis. We measured brachial-ankle pulse wave
      velocity (baPWV) and carotid augmentation index (AIx) as arterial stiffness
      parameters. RESULTS: Peak early diastolic mitral annular velocity (e') was
      significantly correlated with baPWV (men: r = -0.428, P < 0.001; women: r = 
      0.515, P < 0.001) and carotid AIx (men: r = -0.295, P = 0.004; women: r = -0.558,
      P < 0.001). The ratio of early diastolic mitral flow velocity to e' (E/e') was
      significantly correlated with both arterial stiffness parameters in women but not
      men. Multivariable regression analysis revealed carotid AIx (beta = -0.257; P =
      0.02) was a significant independent predictor of e' in women but not men.
      CONCLUSIONS: These results suggest that the correlation between AIx and LV
      diastolic function is stronger in women than men in a healthy population.

PMID- 23864587
TI  - Lissencephaly with brainstem and cerebellar hypoplasia and congenital cataracts.

PMID- 23864589
TI  - Obstetric brachial plexus palsy following routine versus difficult deliveries.
AB  - Previous bio-engineering studies showed that intrapartum peak forces applied by
      the clinician were lower in routine deliveries than difficult deliveries. A total
      of 751 cases of obstetric brachial plexus palsy were included and divided into
      two groups: group I (248 patients) were born following routine deliveries and
      group II (503 patients) were born following difficult deliveries. Both groups
      were compared regarding the type of palsy and the rate of good/poor spontaneous
      motor recovery from the palsy. Group I subjects were more likely to have upper
      Erb palsy whereas those in group II were more likely to develop total palsy (P <
      .0001). The percentage of newborns with poor functional recovery was
      significantly higher (P < .05) in group II with regards to shoulder, wrist, and
      hand function. It was concluded that higher peak forces applied by the clinician
      in difficult deliveries affect the type of obstetric brachial plexus palsy. 

PMID- 23864588
TI  - Hemisphere differences in speech-sound event-related potentials in intensive care
      neonates: associations and predictive value for development in infancy.
AB  - Neurodevelopmental delays in intensive care neonates are common but difficult to
      predict. In children, hemisphere differences in cortical processing of speech are
      predictive of cognitive performance. We hypothesized that hemisphere differences
      in auditory event-related potentials in intensive care neonates are predictive of
      neurodevelopment in infancy, even in those born preterm. Event-related potentials
      to speech sounds were prospectively recorded in 57 infants (gestational age 24-40
      weeks) prior to discharge. The Developmental Assessment of Young Children was
      performed at 6 and 12 months. Hemisphere differences in mean amplitudes increased
      with postnatal age (P < .01) but not with gestational age. Greater hemisphere
      differences were associated with improved communication and cognitive scores at 6
      and 12 months, but decreased in significance at 12 months after adjusting for
      socioeconomic and clinical factors. Auditory cortical responses can be used in
      intensive care neonates to help identify infants at higher risk for delays in
      infancy. 

PMID- 23864590
TI  - Blindness from late presenting undiagnosed pancraniosynostosis mimicking
      pseudotumor cerebri.
AB  - We report the unique case of late-onset pancraniosynostosis presenting with rapid
      visual deterioration, without other symptoms of increased intracranial pressure.
      A 10-year-old girl had episodes of blurry vision for 1 month. Magnetic resonance
      imaging (MRI) demonstrated a borderline Chiari I malformation. Ophthalmologic
      exam confirmed papilledema and decreased visual acuity. Opening pressure on
      lumbar puncture was 55 mmH2O. The patient was diagnosed with pseudotumor cerebri
      and prescribed Diamox. Four days later, she re-presented with worsening vision
      and increased papilledema and was taken for emergent ventriculo-peritoneal shunt
      placement. A postoperative computed tomographic scan showed the absence of all
      cranial sutures. Vision had not improved. A cranial vault expansion and optic
      nerve fenestration was performed. Pancraniosynostosis must be considered in a
      child with rapid visual deterioration and increased intracranial pressure, or
      with the presumptive diagnosis of pseudotumor cerebri. Assurance of normal
      cranial suture anatomy by computed tomographic scan is imperative in patients
      with an atypical presentation of pseudotumor cerebri. 

PMID- 23864591
TI  - Uncommon Leber "plus" disease associated with mitochondrial mutation m.11778G>A
      in a premature child.
AB  - Leber hereditary optic neuropathy is a well-known mitochondrial disorder that
      leads to bilateral subacute visual failure. Although visual impairment is often
      the sole clinical feature, additional and severe neurologic abnormalities also
      have been documented for this disease. We report on a 13-year-old boy who has
      presented with severe visual failure since early childhood in a context of
      prematurity. In the first years of his life, clinical features included delayed
      psychomotor development and ataxia. The clinical presentation, which was
      initially attributed to prematurity, worsened thereafter, and the child developed
      acute neurologic degradation with the typical radiological findings of Leigh
      syndrome. The mitochondrial DNA point mutation 11778G>A was identified in the ND4
      gene. The probable influence of environmental background on clinical expression
      of Leber optic neuropathy, particularly those of prematurity and oxygen therapy,
      is discussed in our manuscript. 

PMID- 23864592
TI  - The stress response to surgery and postoperative delirium: evidence of
      hypothalamic-pituitary-adrenal axis hyperresponsiveness and decreased suppression
      of the GH/IGF-1 Axis.
AB  - INTRODUCTION: The aim of this study is to determine whether postoperative
      delirium is associated with dysregulation of hypothalamic-pituitary-adrenal and
      growth hormone/insulin-like growth factor 1 (GH/IGF-1) responses following acute
      systemic inflammation. METHODS: Plasma levels of cortisol, IGF-1, C-reactive
      protein, interleukin (IL)-6, IL-8, and IL-10 were measured before and after
      surgery in 101 patients >= 60 years without dementia undergoing elective hip
      arthroplasty. Participants were assessed with confusion assessment method and
      Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text
      Revision; DSM-IV-TR) postoperatively and 37 patients fulfilled the DSM-IV-TR
      criteria for delirium. RESULTS: Preoperative plasma cortisol levels were similar
      in delirium and nondelirium groups (405.37 +/- 189.04 vs 461.83 +/- 219.39; P =
      .22). Participants with delirium had higher postoperative cortisol levels (821.67
      +/- 367.17 vs 599.58 +/- 214.94; P = .002) with enhanced postoperative elevation
      in relation to baseline (1.9- vs 1.5-fold; P = .004). The plasma levels of IGF1
      did not differ in delirium and nondelirium groups before (18.12 +/- 7.58 vs 16.8
      +/- 7.86; P = .477) and following surgery (13.39 +/- 5.94 vs 11.12 +/- 6.2; P =
      .639), but the levels increased in relation to baseline more frequently in
      patients who developed delirium (24.3% vs 7.8%; P = .034). The magnitude of
      postoperative cortisol elevation correlated with DeltaIL-6 (P = .485; P = .002),
      DeltaIL-8 (P = .429; P = .008), and DeltaIL-10 (P = .544; P < .001) only in
      patients with delirium. CONCLUSIONS: Hypothalamic-pituitary-adrenal axis
      hyperresponsiveness and a less frequent suppression of the GH/IGF-1 axis in
      response to acute stress are possibly involved in delirium pathophysiology.

PMID- 23864593
TI  - Human mobility patterns predict divergent epidemic dynamics among cities.
AB  - The epidemic dynamics of infectious diseases vary among cities, but it is unclear
      how this is caused by patterns of infectious contact among individuals. Here, we
      ask whether systematic differences in human mobility patterns are sufficient to
      cause inter-city variation in epidemic dynamics for infectious diseases spread by
      casual contact between hosts. We analyse census data on the mobility patterns of
      every full-time worker in 48 Canadian cities, finding a power-law relationship
      between population size and the level of organization in mobility patterns, where
      in larger cities, a greater fraction of workers travel to work in a few focal
      locations. Similarly sized cities also vary in the level of organization in their
      mobility patterns, equivalent on average to the variation expected from a 2.64
      fold change in population size. Systematic variation in mobility patterns is
      sufficient to cause significant differences among cities in infectious disease
      dynamics-even among cities of the same size-according to an individual-based
      model of airborne pathogen transmission parametrized with the mobility data. This
      suggests that differences among cities in host contact patterns are sufficient to
      drive differences in infectious disease dynamics and provides a framework for
      testing the effects of host mobility patterns in city-level disease data. 

PMID- 23864595
TI  - Travelling light: white sharks (Carcharodon carcharias) rely on body lipid stores
      to power ocean-basin scale migration.
AB  - Many species undertake long-distance annual migrations between foraging and
      reproductive areas. Such migrants depend on the efficient packaging, storage and
      utilization of energy to succeed. A diverse assemblage of organisms accomplishes
      this through the use of lipid reserves; yet, it remains unclear whether the
      migrations of elasmobranchs, which include the largest gill breathers on Earth,
      depend on such a mechanism. We examine depth records from pop-up satellite
      archival tags to discern changes in buoyancy as a proxy for energy storage in
      Eastern Pacific white sharks, and assess whether lipid depletion fuels long
      distance (approx. 4000 km) migrations. We develop new algorithms to assess body
      condition, buoyancy and drift rate during drift dives and validate the techniques
      using a captive white shark. In the wild, we document a consistent increase in
      drift rate over the course of all migrations, indicating a decrease in buoyancy
      caused by the depletion of lipid reserves. These results comprise, to our
      knowledge, the first assessment of energy storage and budgeting in migrating
      sharks. The methods provide a basis for further insights into using electronic
      tags to reveal the energetic strategies of a wide range of elasmobranchs. 

PMID- 23864594
TI  - Reproductive competence: a recurrent logic module in eukaryotic development.
AB  - Developmental competence is the ability to differentiate in response to an
      appropriate stimulus, as first elaborated by Waddington in relation to organs and
      tissues. Competence thresholds operate at all levels of biological systems from
      the molecular (e.g. the cell cycle) to the ontological (e.g. metamorphosis and
      reproduction). Reproductive competence, an organismal process, is well studied in
      mammals (sexual maturity) and plants (vegetative phase change), though far less
      than later stages of terminal differentiation. The phenomenon has also been
      documented in multiple species of multicellular fungi, mostly in early, disparate
      literature, providing a clear example of physiological differentiation in the
      absence of morphological change. This review brings together data on reproductive
      competence in Ascomycete fungi, particularly the model filamentous fungus
      Aspergillus nidulans, contrasting mechanisms within Unikonts and plants. We posit
      reproductive competence is an elementary logic module necessary for coordinated
      development of multicellular organisms or functional units. This includes unitary
      multicellular life as well as colonial species both unicellular and multicellular
      (e.g. social insects such as ants). We discuss adaptive hypotheses for
      developmental and reproductive competence systems and suggest experimental work
      to address the evolutionary origins, generality and genetic basis of competence
      in the fungal kingdom. 

PMID- 23864596
TI  - Sexual selection accelerates signal evolution during speciation in birds.
AB  - Sexual selection is proposed to be an important driver of diversification in
      animal systems, yet previous tests of this hypothesis have produced mixed results
      and the mechanisms involved remain unclear. Here, we use a novel phylogenetic
      approach to assess the influence of sexual selection on patterns of evolutionary
      change during 84 recent speciation events across 23 passerine bird families. We
      show that elevated levels of sexual selection are associated with more rapid
      phenotypic divergence between related lineages, and that this effect is
      restricted to male plumage traits proposed to function in mate choice and species
      recognition. Conversely, we found no evidence that sexual selection promoted
      divergence in female plumage traits, or in male traits related to foraging and
      locomotion. These results provide strong evidence that female choice and male
      male competition are dominant mechanisms driving divergence during speciation in
      birds, potentially linking sexual selection to the accelerated evolution of pre
      mating reproductive isolation. 

PMID- 23864598
TI  - A remarkable short-snouted horned dinosaur from the Late Cretaceous (late
      Campanian) of southern Laramidia.
AB  - The fossil record of centrosaurine ceratopsids is largely restricted to the
      northern region of western North America (Alberta, Montana and Alaska).
      Exceptions consist of single taxa from Utah (Diabloceratops) and China
      (Sinoceratops), plus otherwise fragmentary remains from the southern Western
      Interior of North America. Here, we describe a remarkable new taxon,
      Nasutoceratops titusi n. gen. et sp., from the late Campanian Kaiparowits
      Formation of Utah, represented by multiple specimens, including a nearly complete
      skull and partial postcranial skeleton. Autapomorphies include an enlarged narial
      region, pneumatic nasal ornamentation, abbreviated snout and elongate,
      rostrolaterally directed supraorbital horncores. The subrectangular
      parietosquamosal frill is relatively unadorned and broadest in the mid-region. A
      phylogenetic analysis indicates that Nasutoceratops is the sister taxon to
      Avaceratops, and that a previously unknown subclade of centrosaurines branched
      off early in the group's history and persisted for several million years during
      the late Campanian. As the first well-represented southern centrosaurine
      comparable in age to the bulk of northern forms, Nasutoceratops provides strong
      support for the provincialism hypothesis, which posits that Laramidia-the western
      landmass formed by inundation of the central region of North America by the
      Western Interior Seaway-hosted at least two coeval dinosaur communities for over
      a million years of late Campanian time. 

PMID- 23864597
TI  - Androgenesis is a maternal trait in the invasive ant Wasmannia auropunctata.
AB  - Androgenesis is the production of an offspring containing exclusively the nuclear
      genome of the fathering male via the maternal eggs. This unusual mating system is
      generally considered a male trait, giving to androgenetic males a substantial
      fitness advantage over their sexually reproducing relatives. We here provide the
      first empirical study of the evolutionary outcomes of androgenesis in a haplo
      diploid organism: the invasive ant Wasmannia auropunctata. Some of the
      populations of this species have a classical haplo-diploid sexual mating system.
      In other populations, females and males are produced through parthenogenesis and
      androgenesis, respectively, whereas workers are produced sexually. We conducted
      laboratory reciprocal-cross experiments with reproductive individuals from both
      types of populations and analysed their progenies with genetic markers, to
      determine the respective contribution of males and females to the production of
      androgenetic males. We found that androgenesis was a parthenogenetic female
      trait. A population genetic study conducted in natura confirmed the
      parthenogenetic female origin of androgenesis, with the identification of
      introgression events of sexual male genotypes into androgenetic/parthenogenetic
      lineages. We argue that by producing males via androgenesis, parthenogenetic
      queen lineages may increase and/or maintain their adaptive potential, while
      maintaining the integrity of their own genome, by occasionally acquiring new male
      genetic material and avoiding inbreeding depression within the sexually produced
      worker cast. 

PMID- 23864599
TI  - An early fossil remora (Echeneoidea) reveals the evolutionary assembly of the
      adhesion disc.
AB  - The adhesion disc of living remoras (Echeneoidea: Echeneidae) represents one of
      the most remarkable structural innovations within fishes. Although homology
      between the spinous dorsal fin of generalized acanthomorph fishes and the remora
      adhesion disc is widely accepted, the sequence of evolutionary-rather than
      developmental-transformations leading from one to the other has remained unclear.
      Here, we show that the early remora ?Opisthomyzon (Echeneoidea:
      ?Opisthomyzonidae), from the early Oligocene (Rupelian) of Switzerland, is a stem
      group echeneid and provides unique insights into the evolutionary assembly of the
      unusual body plan characteristic of all living remoras. The adhesion disc of
      ?Opisthomyzon retains ancestral features found in the spiny dorsal fins of remora
      outgroups, and corroborates developmental interpretations of the homology of
      individual skeletal components of the disc. ?Opisthomyzon indicates that the
      adhesion disc originated in a postcranial position, and that other
      specializations (including the origin of pectination, subdivision of median fin
      spines into paired lamellae, increase in segment count and migration to a
      supracranial position) took place later in the evolutionary history of remoras.
      This phylogenetic sequence of transformation finds some parallels in the order of
      ontogenetic changes to the disc documented for living remoras. 

PMID- 23864600
TI  - Colour cues proved to be more informative for dogs than brightness.
AB  - The results of early studies on colour vision in dogs led to the conclusion that
      chromatic cues are unimportant for dogs during their normal activities.
      Nevertheless, the canine retina possesses two cone types which provide at least
      the potential for colour vision. Recently, experiments controlling for the
      brightness information in visual stimuli demonstrated that dogs have the ability
      to perform chromatic discrimination. Here, we show that for eight previously
      untrained dogs colour proved to be more informative than brightness when choosing
      between visual stimuli differing both in brightness and chromaticity. Although
      brightness could have been used by the dogs in our experiments (unlike previous
      studies), it was not. Our results demonstrate that under natural photopic
      lighting conditions colour information may be predominant even for animals that
      possess only two spectral types of cone photoreceptors. 

PMID- 23864601
TI  - Trophic omnivory across a productivity gradient: intraguild predation theory and
      the structure and strength of species interactions.
AB  - Intraguild predation theory centres on two predictions: (i) for an omnivore and
      an intermediate predator (IG-prey) to coexist on shared resources, the IG-prey
      must be the superior resource competitor, and (ii) increasing resource
      productivity causes the IG-prey's equilibrium abundance to decline. I tested
      these predictions with a series of species-rich food webs along New Zealand's
      rocky shores, focusing on two predatory whelks, Haustrum haustorium, a trophic
      omnivore, and Haustrum scobina, the IG-prey. In contrast to theory, the IG-prey's
      abundance increased with productivity. Furthermore, feeding rates and allometric
      considerations indicate a competitive advantage for the omnivore when non-shared
      prey are considered, despite the IG-prey's superiority for shared prey.
      Nevertheless, clear and regular cross-gradient changes in network structure and
      interaction strengths were observed that challenge the assumptions of current
      theory. These insights suggest that the consideration of consumer-dependent
      functional responses, non-equilibrium dynamics, the dynamic nature of prey choice
      and non-trophic interactions among basal prey will be fruitful avenues for
      theoretical development. 

PMID- 23864602
TI  - Eyespots divert attacks by fish.
AB  - Eyespots (colour patterns consisting of concentric rings) are found in a wide
      range of animal taxa and are often assumed to have an anti-predator function.
      Previous experiments have found strong evidence for an intimidating effect of
      eyespots against passerine birds. Some eyespots have been suggested to increase
      prey survival by diverting attacks towards less vital body parts or a direction
      that would facilitate escape. While eyespots in aquatic environments are
      widespread, their function is extremely understudied. Therefore, we investigated
      the protective function of eyespots against attacking fish. We used artificial
      prey and predator-naive three-spined sticklebacks (Gasterosteus aculeatus) as
      predators to test both the diversion (deflection) and the intimidation
      hypothesis. Interestingly, our results showed that eyespots smaller than the
      fish' own eye very effectively draw the attacks of the fish towards them.
      Furthermore, our experiment also showed that this was not due to the
      conspicuousness of the eyespot, because attack latency did not differ between
      prey items with and without eyespots. We found little support for an intimidating
      effect by larger eyespots. Even though also other markings might misdirect
      attacks, we can conclude that the misdirecting function may have played an
      important role in the evolution of eyespots in aquatic environments. 

PMID- 23864603
TI  - The excuse principle can maintain cooperation through forgivable defection in the
      Prisoner's Dilemma game.
AB  - Reciprocal altruism describes a situation in which an organism acts in a manner
      that temporarily reduces its fitness while increasing another organism's fitness,
      but there is an ultimate fitness benefit based on an expectation that the other
      organism will act in a similar manner at a later time. It creates the obvious
      dilemma in which there is always a short-term benefit to cheating, therefore
      cooperating individuals must avoid being exploited by non-cooperating cheaters.
      This is achieved by following various decision rules, usually variants of the tit
      for-tat (TFT) strategy. The strength of TFT, however, is also its weakness
      mistakes in implementation or interpretation of moves, or the inability to
      cooperate, lead to a permanent breakdown in cooperation. We show that pied
      flycatchers (Ficedula hypoleuca) use a TFT with an embedded 'excuse principle' to
      forgive the neighbours that were perceived as unable to cooperate during mobbing
      of predators. The excuse principle dramatically increases the stability of TFT
      like behavioural strategies within the Prisoner's Dilemma game. 

PMID- 23864604
TI  - Time for T...(T3, T4, rT3)? Focus on "Acute inhibition of the cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl- channel by thyroid hormones
      involves multiple mechanisms".

PMID- 23864605
TI  - Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases
      the trafficking of Kv11.1 channels stored in the transitional endoplasmic
      reticulum.
AB  - KCNH2 encodes Kv11.1 and underlies the rapidly activating delayed rectifier K(+)
      current (IKr) in the heart. Loss-of-function KCNH2 mutations cause the type 2
      long QT syndrome (LQT2), and most LQT2-linked missense mutations inhibit the
      trafficking of Kv11.1 channels. Drugs that bind to Kv11.1 and block IKr (e.g., E
      4031) can act as pharmacological chaperones to increase the trafficking and
      functional expression for most LQT2 channels (pharmacological correction). We
      previously showed that LQT2 channels are selectively stored in a microtubule
      dependent compartment within the endoplasmic reticulum (ER). We tested the
      hypothesis that pharmacological correction promotes the trafficking of LQT2
      channels stored in this compartment. Confocal analyses of cells expressing the
      trafficking-deficient LQT2 channel G601S showed that the microtubule-dependent ER
      compartment is the transitional ER. Experiments with E-4031 and the protein
      synthesis inhibitor cycloheximide suggested that pharmacological correction
      promotes the trafficking of G601S stored in this compartment. Treating cells in E
      4031 or ranolazine (a drug that blocks IKr and has a short half-life) for 30 min
      was sufficient to cause pharmacological correction. Moreover, the increased
      functional expression of G601S persisted 4-5 h after drug washout. Coexpression
      studies with a dominant-negative form of Rab11B, a small GTPase that regulates
      Kv11.1 trafficking, prevented the pharmacological correction of G601S trafficking
      from the transitional ER. These data suggest that pharmacological correction
      quickly increases the trafficking of LQT2 channels stored in the transitional ER
      via a Rab11B-dependent pathway, and we conclude that the pharmacological
      chaperone activity of drugs like ranolazine might have therapeutic potential.

PMID- 23864606
TI  - SLC4A11 is an EIPA-sensitive Na(+) permeable pHi regulator.
AB  - Slc4a11, a member of the solute linked cotransporter 4 family that is comprised
      predominantly of bicarbonate transporters, was described as an electrogenic
      2Na(+)-B(OH)4(-) (borate) cotransporter and a Na(+)-2OH(-) cotransporter. The
      goal of the current study was to confirm and/or clarify the function of SLC4A11.
      In HEK293 cells transfected with SLC4A11 we tested if SLC4A11 is a: 1) Na(+)
      HCO3(-) cotransporter, 2) Na(+)-OH(-)(H(+)) transporter, and/or 3) Na(+)-B(OH)4(
      ) cotransporter. CO2/HCO3(-) perfusion yielded no significant differences in rate
      or extent of pHi changes or Na(+) flux in SLC4A11-transfected compared with
      control cells. Similarly, in CO2/HCO3(-), acidification on removal of Na(+) and
      alkalinization on Na(+) add back were not significantly different between control
      and transfected indicating that SLC4A11 does not have Na(+)-HCO3(-) cotransport
      activity. In the absence of CO2/HCO3(-), SLC4A11-transfected cells showed higher
      resting intracelllular Na(+) concentration ([Na(+)]i; 25 vs. 17 mM), increased
      NH4(+)-induced acidification and increased acid recovery rate (160%) after an NH4
      pulse. Na(+) efflux and influx were faster (80%) following Na(+) removal and add
      back, respectively, indicative of Na(+)-OH(-)(H(+)) transport by SLC4A11. The
      increased alkalinization recovery was confirmed in NHE-deficient PS120 cells
      demonstrating that SLC4A11 is a bonafide Na(+)-OH(-)(H(+)) transporter and not an
      activator of NHEs. SLC4A11-mediated H(+) efflux is inhibited by 5-(N-ethyl-N
      isopropyl) amiloride (EIPA; EC50: 0.1 MUM). The presence of 10 mM borate did not
      alter dpHi/dt or DeltapH during a Na(+)-free pulse in SLC4A11-transfected cells.
      In summary our results show that SLC4A11 is not a bicarbonate or borate-linked
      transporter but has significant EIPA-sensitive Na(+)-OH(-)(H(+)) and NH4(+)
      permeability.

PMID- 23864607
TI  - Age-related changes in the features of porcine adult stem cells isolated from
      adipose tissue and skeletal muscle.
AB  - A better understanding of the control of body fat distribution and muscle
      development is of the upmost importance for both human and animal physiology.
      This requires a better knowledge of the features and physiology of adult stem
      cells in adipose tissue and skeletal muscle. Thus the objective of the current
      study was to determine the type and proportion of these cells in growing and
      adult pigs. The different cell subsets of stromal vascular cells isolated from
      these tissues were characterized by flow cytometry using cell surface markers
      (CD11b, CD14, CD31, CD34, CD45, CD56, and CD90). Adipose and muscle cells were
      predominantly positive for the CD34, CD56, and CD90 markers. The proportion of
      positive cells changed with age especially in intermuscular adipose tissue and
      skeletal muscle where the percentage of CD90(+) cells markedly increased in adult
      animals. Further analysis using coimmunostaining indicates that eight populations
      with proportions ranging from 12 to 30% were identified in at least one tissue at
      7 days of age, i.e., CD90(+)/CD34(+), CD90(+)/CD34(-), CD90(+)/CD56(+),
      CD90(+)/CD56(-), CD90(-)/CD56(+), CD56(+)/CD34(+), CD56(+)/CD34(-), and CD56(
      )/CD34(+). Adipose tissues appeared to be a less heterogeneous tissue than
      skeletal muscle with two main populations (CD90(+)/CD34(-) and CD90(+)/CD56(-))
      compared with five or more in muscle during the studied period. In culture, cells
      from adipose tissue and muscle differentiated into mature adipocytes in
      adipogenic medium. In myogenic conditions, only cells from muscle could form
      mature myofibers. Further studies are now needed to better understand the
      plasticity of those cell populations throughout life.

PMID- 23864608
TI  - Cyclic AMP-Rap1A signaling mediates cell surface translocation of microvascular
      smooth muscle alpha2C-adrenoceptors through the actin-binding protein filamin-2.
AB  - The second messenger cyclic AMP (cAMP) plays a vital role in vascular physiology,
      including vasodilation of large blood vessels. We recently demonstrated cAMP
      activation of Epac-Rap1A and RhoA-Rho-associated kinase (ROCK)-F-actin signaling
      in arteriolar-derived smooth muscle cells increases expression and cell surface
      translocation of functional alpha2C-adrenoceptors (alpha2C-ARs) that mediate
      vasoconstriction in small blood vessels (arterioles). The Ras-related small
      GTPAse Rap1A increased expression of alpha2C-ARs and also increased translocation
      of perinuclear alpha2C-ARs to intracellular F-actin and to the plasma membrane.
      This study examined the mechanism of translocation to better understand the role
      of these newly discovered mediators of blood flow control, potentially activated
      in peripheral vascular disorders. We utilized a yeast two-hybrid screen with
      human microvascular smooth muscle cells (microVSM) cDNA library and the alpha2C
      AR COOH terminus to identify a novel interaction with the actin cross-linker
      filamin-2. Yeast alpha-galactosidase assays, site-directed mutagenesis, and
      coimmunoprecipitation experiments in heterologous human embryonic kidney (HEK)
      293 cells and in human microVSM demonstrated that alpha2C-ARs, but not alpha2A-AR
      subtype, interacted with filamin. In Rap1-stimulated human microVSM, alpha2C-ARs
      colocalized with filamin on intracellular filaments and at the plasma membrane.
      Small interfering RNA-mediated knockdown of filamin-2 inhibited Rap1-induced
      redistribution of alpha2C-ARs to the cell surface and inhibited receptor
      function. The studies suggest that cAMP-Rap1-Rho-ROCK signaling facilitates
      receptor translocation and function via phosphorylation of filamin-2 Ser(2113).
      Together, these studies extend our previous findings to show that functional
      rescue of alpha2C-ARs is mediated through Rap1-filamin signaling. Perturbation of
      this signaling pathway may lead to alterations in alpha2C-AR trafficking and
      physiological function. 

PMID- 23864610
TI  - Transport of H2S and HS(-) across the human red blood cell membrane: rapid H2S
      diffusion and AE1-mediated Cl(-)/HS(-) exchange.
AB  - The rates of H2S and HS(-) transport across the human erythrocyte membrane were
      estimated by measuring rates of dissipation of pH gradients in media containing
      250 MUM H2S/HS(-). Net acid efflux is caused by H2S/HS(-) acting analogously to
      CO2/HCO3(-) in the Jacobs-Stewart cycle. The steps are as follows: 1) H2S efflux
      through the lipid bilayer and/or a gas channel, 2) extracellular H2S
      deprotonation, 3) HS(-) influx in exchange for Cl(-), catalyzed by the anion
      exchange protein AE1, and 4) intracellular HS(-) protonation. Net acid transport
      by the Cl(-)/HS(-)/H2S cycle is more efficient than by the Cl(-)/HCO3(-)/CO2
      cycle because of the rapid H2S-HS(-) interconversion in cells and medium. The
      rates of acid transport were analyzed by solving the mass flow equations for the
      cycle to produce estimates of the HS(-) and H2S transport rates. The data
      indicate that HS(-) is a very good substrate for AE1; the Cl(-)/HS(-) exchange
      rate is about one-third as rapid as Cl(-)/HCO3(-) exchange. The H2S permeability
      coefficient must also be high (>10(-2) cm/s, half time <0.003 s) to account for
      the pH equilibration data. The results imply that H2S and HS(-) enter
      erythrocytes very rapidly in the microcirculation of H2S-producing tissues,
      thereby acting as a sink for H2S and lowering the local extracellular
      concentration, and the fact that HS(-) is a substrate for a Cl(-)/HCO3(-)
      exchanger indicates that some effects of exogenous H2S/HS(-) may not result from
      a regulatory role of H2S but, rather, from net acid flux by H2S and HS(-)
      transport in a Jacobs-Stewart cycle.

PMID- 23864611
TI  - Association of the vaccinia virus A11 protein with the endoplasmic reticulum and
      crescent precursors of immature virions.
AB  - The apparent de novo formation of viral membranes within cytoplasmic factories is
      a mysterious, poorly understood first step in poxvirus morphogenesis. Genetic
      studies identified several viral proteins essential for membrane formation and
      the assembly of immature virus particles. Their repression results in abortive
      replication with the accumulation of dense masses of viroplasm. In the present
      study, we further characterized one of these proteins, A11, and investigated its
      association with cellular and viral membranes under normal and abortive
      replication conditions. We discovered that A11 colocalized in cytoplasmic
      factories with the endoplasmic reticulum (ER) and L2, another viral protein
      required for morphogenesis. Confocal microscopy and subcellular fractionation
      indicated that A11 was not membrane associated in uninfected cells, whereas L2
      still colocalized with the ER. Cell-free transcription and translation
      experiments indicated that both A11 and L2 are tail-anchored proteins that
      associate posttranslationally with membranes and likely require specific
      cytoplasmic targeting chaperones. Transmission electron microscopy indicated that
      A11, like L2, associated with crescent membranes and immature virions during
      normal infection and with vesicles and tubules near masses of dense viroplasm
      during abortive infection in the absence of the A17 or A14 protein component of
      viral membranes. When the synthesis of A11 was repressed, "empty" immature-virion
      like structures formed in addition to masses of viroplasm. The immature-virion
      like structures were labeled with antibodies to A17 and to the D13 scaffold
      protein and were closely associated with calnexin-labeled ER. These studies
      revealed similarities and differences between A11 and L2, both of which may be
      involved in the recruitment of the ER for virus assembly. 

PMID- 23864609
TI  - Resolvin D1 protects periodontal ligament.
AB  - Resolution agonists are endogenous mediators that drive inflammation to
      homeostasis. We earlier demonstrated in vivo activity of resolvins and lipoxins
      on regenerative periodontal wound healing. The goal of this study was to
      determine the impact of resolvin D1 (RvD1) on the function of human periodontal
      ligament (PDL) fibroblasts, which are critical for wound healing during
      regeneration of the soft and hard tissues around teeth. Primary cells were
      cultured from biopsies obtained from three individuals free of periodontal
      diseases. Peripheral blood mononuclear cells were isolated by density gradient
      centrifugation from whole blood of healthy volunteers. PGE2, leukotriene B4
      (LTB4), and lipoxin A4 (LXA4) in culture supernatants were measured by ELISA. The
      direct impact of RvD1 on PDL fibroblast proliferation was measured and wound
      closure was analyzed in vitro using a fibroblast culture "scratch assay." PDL
      fibroblast function in response to RvD1 was further characterized by basic FGF
      production by ELISA. IL-1beta and TNF-alpha enhanced the production of PGE2.
      Treatment of PDL cells and monocytes with 0.1-10 ng/ml RvD1 (0.27-27 M) reduced
      cytokine induced production of PGE2 and upregulated LXA4 production by both PDL
      cells and monocytes. RvD1 significantly enhanced PDL fibroblast proliferation and
      wound closure as well as basic FGF release. The results demonstrate that anti
      inflammatory and proresolution actions of RvD1 with upregulation of arachidonic
      acid-derived endogenous resolution pathways (LXA4) and suggest resolution pathway
      synergy establishing a novel mechanism for the proresolution activity of the
      omega-3 docosahexaenoic acid-derived resolution agonist RvD1. 

PMID- 23864612
TI  - A novel rabbit monoclonal antibody platform to dissect the diverse repertoire of
      antibody epitopes for HIV-1 Env immunogen design.
AB  - The majority of available monoclonal antibodies (MAbs) in the current HIV vaccine
      field are generated from HIV-1-infected people. In contrast, preclinical
      immunogenicity studies have mainly focused on polyclonal antibody responses in
      experimental animals. Although rabbits have been widely used for antibody
      studies, there has been no report of using rabbit MAbs to dissect the specificity
      of antibody responses for AIDS vaccine development. Here we report on the
      production of a panel of 12 MAbs from a New Zealand White (NZW) rabbit that was
      immunized with an HIV-1 JR-FL gp120 DNA prime and protein boost vaccination
      regimen. These rabbit MAbs recognized a diverse repertoire of envelope (Env)
      epitopes ranging from the highly immunogenic V3 region to several previously
      underappreciated epitopes in the C1, C4, and C5 regions. Nine MAbs showed cross
      reactivity to gp120s of clades other than clade B. Increased somatic mutation and
      extended CDR3 were observed with Ig genes of several molecularly cloned rabbit
      MAbs. Phylogenic tree analysis showed that the heavy chains of MAbs recognizing
      the same region on gp120 tend to segregate into an independent subtree. At least
      three rabbit MAbs showed neutralizing activities with various degrees of breadth
      and potency. The establishment of this rabbit MAb platform will significantly
      enhance our ability to test optimal designs of Env immunogens to gain a better
      understanding of the structural specificity and evolution process of Env-specific
      antibody responses elicited by candidate AIDS vaccines. 

PMID- 23864613
TI  - Mammalian adaptation in the PB2 gene of avian H5N1 influenza virus.
AB  - The substitution of glutamic acid (E) for lysine (K) at position 627 of the PB2
      protein of avian H5N1 viruses has been identified as a virulence and host range
      determinant for infection of mammals. Here, we report that the E-to-K host
      adaptive mutation in the PB2 gene appeared from day 4 and 5 along the respiratory
      tracts of mice and was complete by day 6 postinoculation. This mutation
      correlated with efficient replication of the virus in mice. 

PMID- 23864614
TI  - Presentation overrides specificity: probing the plasticity of alphaviral
      proteolytic activity through mutational analysis.
AB  - Semliki Forest virus (genus Alphavirus) is an important model for studying
      regulated nonstructural (ns) polyprotein processing. In this study, we evaluated
      the strictness of the previously outlined cleavage rules, accounting for the
      timing and outcome of each of three cleavages within the ns polyprotein P1234,
      and assessed the significance of residues P6 to P4 within the cleavage sites
      using an alanine scanning approach. The processing of the 1/2 and 3/4 sites was
      most strongly affected following changes in residues P5 and P4, respectively.
      However, none of the mutations had a detectable effect on the processing of the
      2/3 site. An analysis of recombinant viruses bearing combinations of mutations in
      cleavage sites revealed tolerance toward the cooccurrence of native and mutated
      cleavage sites within the same polyprotein, suggesting a remarkable plasticity of
      the protease recognition pocket. Even in a virus in which all of the cleavage
      sequences were replaced with alanines in the P6, P5, and P4 positions, the
      processing pattern was largely preserved, without leading to reversion of
      cleavage site mutations. Instead, the emergence of second-site mutations was
      identified, among which Q706R/L in nsP2 was confirmed to be associated with the
      recognition of the P4 position within the modified cleavage sites. Our results
      imply that the spatial arrangement of the viral replication complex inherently
      contributes to scissile-site presentation for the protease, alleviating stringent
      sequence recognition requirements yet ensuring the precision and the correct
      order of processing events. Obtaining a proper understanding of the consequences
      of cleavage site manipulations may provide new tools for taming alphaviruses. 

PMID- 23864616
TI  - Uncoupling of influenza A virus transcription and replication through mutation of
      the unpaired adenosine in the viral RNA promoter.
AB  - Transcription and replication of the influenza A virus RNA genome are mediated by
      the viral RNA polymerase from a promoter consisting of the partially base-paired
      3' and 5' termini of viral genome segments. Here we show that transcription and
      replication can be uncoupled by mutation of an unpaired adenosine in the 5'
      strand of the promoter. This residue is important for transcription but not
      replication by being essential for the cap-binding activity of the RNA
      polymerase. 

PMID- 23864615
TI  - The short stalk length of highly pathogenic avian influenza H5N1 virus
      neuraminidase limits transmission of pandemic H1N1 virus in ferrets.
AB  - H5N1 influenza viruses pose a pandemic threat but have not acquired the ability
      to support sustained transmission between mammals in nature. The restrictions to
      transmissibility of avian influenza viruses in mammals are multigenic, and
      overcoming them requires adaptations in hemagglutinin (HA) and PB2 genes. Here we
      propose that a further restriction to mammalian transmission of the majority of
      highly pathogenic avian influenza (HPAI) H5N1 viruses may be the short stalk
      length of the neuraminidase (NA) protein. This genetic feature is selected for
      when influenza viruses adapt to chickens. In our study, a recombinant virus with
      seven gene segments from a human isolate of the 2009 H1N1 pandemic combined with
      the NA gene from a typical chicken-adapted H5N1 virus with a short stalk did not
      support transmission by respiratory droplet between ferrets. This virus was also
      compromised in multicycle replication in cultures of human airway epithelial
      cells at 32 degrees C. These defects correlated with a reduction in the ability
      of virus with a short-stalk NA to penetrate mucus and deaggregate virions. The
      deficiency in transmission and in cleavage of tethered substrates was overcome by
      increasing the stalk length of the NA protein. These observations suggest that
      H5N1 viruses that acquire a long-stalk NA through reassortment might be more
      likely to support transmission between humans. Phylogenetic analysis showed that
      reassortment with long-stalk NA occurred sporadically and as recently as 2011.
      However, all identified H5N1 viruses with a long-stalk NA lacked other mammalian
      adapting features and were thus several genetic steps away from becoming
      transmissible between humans. 

PMID- 23864617
TI  - Mode of virus rescue determines the acquisition of VHS mutations in VP22-negative
      herpes simplex virus 1.
AB  - It has been proposed that herpes simplex virus 1 with VP22 deleted requires
      secondary mutation of VHS for viability. Here we show that a replication
      competent Delta22 virus constructed by homologous recombination maintains a wild
      type (Wt) VHS gene and has no other gross mutations. By contrast, Delta22 viruses
      recovered from a bacterial artificial chromosome contain multiple amino acid
      changes within a conserved region of VHS. Hence, the mode of virus rescue
      influences the acquisition of secondary mutations. 

PMID- 23864618
TI  - Human cytomegalovirus interleukin-10 polarizes monocytes toward a deactivated M2c
      phenotype to repress host immune responses.
AB  - Several human cytomegalovirus (HCMV) genes encode products that modulate cellular
      functions in a manner likely to enhance viral pathogenesis. This includes UL111A,
      which encodes homologs of human interleukin-10 (hIL-10). Depending upon signals
      received, monocytes and macrophages become polarized to either classically
      activated (M1 proinflammatory) or alternatively activated (M2 anti-inflammatory)
      subsets. Skewing of polarization toward an M2 subset may benefit the virus by
      limiting the proinflammatory responses to infection, and so we determined whether
      HCMV-encoded viral IL-10 influenced monocyte polarization. Recombinant viral IL
      10 protein polarized CD14(+) monocytes toward an anti-inflammatory M2 subset with
      an M2c phenotype, as demonstrated by high expression of CD163 and CD14 and
      suppression of major histocompatibility complex (MHC) class II. Significantly, in
      the context of productive HCMV infection, viral IL-10 produced by infected cells
      polarized uninfected monocytes toward an M2c phenotype. We also assessed the
      impact of viral IL-10 on heme oxygenase 1 (HO-1), which is an enzyme linked with
      suppression of inflammatory responses. Polarization of monocytes by viral IL-10
      resulted in upregulation of HO-1, and inhibition of HO-1 function resulted in a
      loss of capacity of viral IL-10 to suppress tumor necrosis factor alpha (TNF
      alpha) and IL-1beta, implicating HO-1 in viral IL-10-induced suppression of
      proinflammatory cytokines by M2c monocytes. In addition, a functional consequence
      of monocytes polarized with viral IL-10 was a decreased capacity to activate
      CD4(+) T cells. This study identifies a novel role for viral IL-10 in driving M2c
      polarization, which may limit virus clearance by restricting proinflammatory and
      CD4(+) T cell responses at sites of infection. 

PMID- 23864619
TI  - The HEX1 gene of Fusarium graminearum is required for fungal asexual reproduction
      and pathogenesis and for efficient viral RNA accumulation of Fusarium graminearum
      virus 1.
AB  - The accumulation of viral RNA depends on many host cellular factors. The
      hexagonal peroxisome (Hex1) protein is a fungal protein that is highly expressed
      when the DK21 strain of Fusarium graminearum virus 1 (FgV1) infects its host, and
      Hex1 affects the accumulation of FgV1 RNA. The Hex1 protein is the major
      constituent of the Woronin body (WB), which is a peroxisome-derived electron
      dense core organelle that seals the septal pore in response to hyphal wounding.
      To clarify the role of Hex1 and the WB in the relationship between FgV1 and
      Fusarium graminearum, we generated targeted gene deletion and overexpression
      mutants. Although neither HEX1 gene deletion nor overexpression substantially
      affected vegetative growth, both changes reduced the production of asexual spores
      and reduced virulence on wheat spikelets in the absence of FgV1 infection.
      However, the vegetative growth of deletion and overexpression mutants was
      increased and decreased, respectively, upon FgV1 infection compared to that of an
      FgV1-infected wild-type isolate. Viral RNA accumulation was significantly
      decreased in deletion mutants but was significantly increased in overexpression
      mutants compared to the viral RNA accumulation in the virus-infected wild-type
      control. Overall, these data indicate that the HEX1 gene plays a direct role in
      the asexual reproduction and virulence of F. graminearum and facilitates viral
      RNA accumulation in the FgV1-infected host fungus. 

PMID- 23864621
TI  - The template specificity of bacteriophage Phi6 RNA polymerase.
AB  - Bacteriophage Phi6 contains three double-stranded RNA (dsRNA) genomic segments,
      L, M, and S. The RNA is located inside a core particle composed of multiple
      copies of a major structural protein, an RNA-dependent RNA polymerase, a
      hexameric NTPase, and an auxiliary protein. The virion RNA polymerase in the core
      particle transcribes segments M and S in vitro. Segment L is transcribed poorly
      because its transcript starts with GU instead of GG found on segments S and M.
      Transcription in vivo is modified by the binding of host protein YajQ to the
      outside the core particle so that segment L is transcribed well. This mechanism
      is the determinant of the temporal control of gene expression in Phi6. Mutants of
      Phi6 have been isolated that are independent of YajQ for transcription of segment
      L. The mutations are found in the gene of the viral polymerase or the major
      capsid protein or both. These mutants are capable of transcribing segment L with
      the GU start or GA or GC. The same is found to be true when YajQ is added to wild
      type particles. Minus-strand synthesis has restrictions that are different from
      that of plus-strand synthesis, and YajQ or mutations to independence do not
      modify minus-strand synthesis behavior. Purified polymerase P2 is able to
      transcribe dsRNA, but transcription behavior of segment L by both wild-type and
      mutant polymerases is different from that seen in capsid structures. Adding YajQ
      to purified polymerase does not change its transcription specificity. 

PMID- 23864620
TI  - An inactivated cell culture Japanese encephalitis vaccine (JE-ADVAX) formulated
      with delta inulin adjuvant provides robust heterologous protection against West
      Nile encephalitis via cross-protective memory B cells and neutralizing antibody.
AB  - West Nile virus (WNV), currently the cause of a serious U.S. epidemic, is a
      mosquito-borne flavivirus and member of the Japanese encephalitis (JE)
      serocomplex. There is currently no approved human WNV vaccine, and treatment
      options remain limited, resulting in significant mortality and morbidity from
      human infection. Given the availability of approved human JE vaccines, this study
      asked whether the JE-ADVAX vaccine, which contains an inactivated cell culture JE
      virus antigen formulated with Advax delta inulin adjuvant, could provide
      heterologous protection against WNV infection in wild-type and beta2
      microglobulin-deficient (beta2m(-/-)) murine models. Mice immunized twice or even
      once with JE-ADVAX were protected against lethal WNV challenge even when mice had
      low or absent serum cross-neutralizing WNV titers prior to challenge. Similarly,
      beta2m(-/-) mice immunized with JE-ADVAX were protected against lethal WNV
      challenge in the absence of CD8(+) T cells and prechallenge WNV antibody titers.
      Protection against WNV could be adoptively transferred to naive mice by memory B
      cells from JE-ADVAX-immunized animals. Hence, in addition to increasing serum
      cross-neutralizing antibody titers, JE-ADVAX induced a memory B-cell population
      able to provide heterologous protection against WNV challenge. Heterologous
      protection was reduced when JE vaccine antigen was administered alone without
      Advax, confirming the importance of the adjuvant to induction of cross-protective
      immunity. In the absence of an approved human WNV vaccine, JE-ADVAX could provide
      an alternative approach for control of a major human WNV epidemic. 

PMID- 23864622
TI  - Interaction of herpes simplex virus ICP0 with ND10 bodies: a sequential process
      of adhesion, fusion, and retention.
AB  - On entry into the nucleus, herpes simplex virus 1 (HSV-1) DNA localizes to
      nuclear bodies known as ND10. Gene repression imposed by ND10 is released by a
      viral protein, ICP0, via degradation of the ND10 constituents promyelocytic
      leukemia protein (PML) and Sp100 and the subsequent dispersal of ND10 bodies. In
      order to understand the dynamic interaction between ICP0 and ND10, we carried out
      deletion mapping to identify the domains of ICP0 responsible for its association
      with ND10. Here, we report the following. (i) An ND10 entry signal (ND10-ES),
      located between residues 245 and 474, is required for ICP0 to penetrate and fuse
      with ND10. ICP0 lacking ND10-ES adheres to the surface of ND10 but fails to
      enter. (ii) In the absence of ND10-ES, the E3 ubiquitin ligase of ICP0
      facilitates the transient adhesion of the truncated ICP0 to the ND10 surface,
      whereas the presence of ND10-ES in ICP0 renders ND10 fusion regardless of the E3
      ligase activity. (iii) The C terminus of ICP0 is required for retention of ICP0
      in ND10 but plays no role in the recruitment process. (iv) The adverse effects of
      an inactive RING domain on viral replication are partially reversed by deleting
      either ND10-ES or the C-terminal retention domain, suggesting that additional
      ICP0 functions require the release of ICP0 from ND10. Based on these results, we
      conclude that association of ICP0 and ND10 is a dynamic process, in which three
      sequential steps--adhesion, fusion, and retention--are adopted to stabilize the
      interaction. A faithful execution of these steps defines the ultimate
      productivity of the virus.

PMID- 23864623
TI  - The recent establishment of North American H10 lineage influenza viruses in
      Australian wild waterfowl and the evolution of Australian avian influenza
      viruses.
AB  - Influenza A H10N7 virus with a hemagglutinin gene of North American origin was
      detected in Australian chickens and poultry abattoir workers in New South Wales,
      Australia, in 2010 and in chickens in Queensland, Australia, on a mixed chicken
      and domestic duck farm in 2012. We investigated their genomic origins by
      sequencing full and partial genomes of H10 viruses isolated from wild aquatic
      birds and poultry in Australia and analyzed them with all available avian
      influenza virus sequences from Oceania and representative viruses from North
      America and Eurasia. Our analysis showed that the H10N7 viruses isolated from
      poultry were similar to those that have been circulating since 2009 in Australian
      aquatic birds and that their initial transmission into Australia occurred during
      2007 and 2008. The H10 viruses that appear to have developed endemicity in
      Australian wild aquatic birds were derived from several viruses circulating in
      waterfowl along various flyways. Their hemagglutinin gene was derived from
      aquatic birds in the western states of the United States, whereas the
      neuraminidase was closely related to that from viruses previously detected in
      waterfowl in Japan. The remaining genes were derived from Eurasian avian
      influenza virus lineages. Our analysis of virological data spanning 40 years in
      Oceania indicates that the long-term evolutionary dynamics of avian influenza
      viruses in Australia may be determined by climatic changes. The introduction and
      long-term persistence of avian influenza virus lineages were observed during
      periods with increased rainfall, whereas bottlenecks and extinction were observed
      during phases of widespread decreases in rainfall. These results extend our
      understanding of factors affecting the dynamics of avian influenza and provide
      important considerations for surveillance and disease control strategies. 

PMID- 23864624
TI  - The homologous tripartite viral RNA polymerase of A/swine/Korea/CT1204/2009(H1N2)
      influenza virus synergistically drives efficient replication and promotes
      respiratory droplet transmission in ferrets.
AB  - We previously reported that influenza A/swine/Korea/1204/2009(H1N2) virus was
      virulent and transmissible in ferrets in which the respiratory-droplet
      transmissible virus (CT-Sw/1204) had acquired simultaneous hemagglutinin
      (HAD225G) and neuraminidase (NAS315N) mutations. Incorporating these mutations
      into the nonpathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently
      altered pathogenicity and growth in animal models but could not establish
      efficient transmission or noticeable disease. We therefore exploited various
      reassortants of these two viruses to better understand and identify other viral
      factors responsible for pathogenicity, transmissibility, or both. We found that
      possession of the CT-Sw/1204 tripartite viral polymerase enhanced replicative
      ability and pathogenicity in mice more significantly than did expression of
      individual polymerase subunit proteins. In ferrets, homologous expression of
      viral RNA polymerase complex genes in the context of the mutant Sw/1130 carrying
      the HA225G and NA315N modifications induced optimal replication in the upper
      nasal and lower respiratory tracts and also promoted efficient aerosol
      transmission to respiratory droplet contact ferrets. These data show that the
      synergistic function of the tripartite polymerase gene complex of CT-Sw/1204 is
      critically important for virulence and transmission independent of the surface
      glycoproteins. Sequence comparison results reveal putative differences that are
      likely to be responsible for variation in disease. Our findings may help
      elucidate previously undefined viral factors that could expand the host range and
      disease severity induced by triple-reassortant swine viruses, including the
      A(H1N1)pdm09 virus, and therefore further justify the ongoing development of
      novel antiviral drugs targeting the viral polymerase complex subunits. 

PMID- 23864625
TI  - Oncolytic vesicular stomatitis virus in an immunocompetent model of MUC1-positive
      or MUC1-null pancreatic ductal adenocarcinoma.
AB  - Vesicular stomatitis virus (VSV) is a promising oncolytic agent against various
      malignancies. Here, for the first time, we tested VSV in vitro and in vivo in a
      clinically relevant, immunocompetent mouse model of pancreatic ductal
      adenocarcinoma (PDA). Our system allows the study of virotherapy against PDA in
      the context of overexpression (80% of PDA patients) or no expression of human
      mucin 1 (MUC1), a major marker for poor prognosis in patients. In vitro, we
      tested three VSV recombinants, wild-type VSV, VSV-green fluorescent protein (VSV
      GFP), and a safe oncolytic VSV-DeltaM51-GFP, against five mouse PDA cell lines
      that either expressed human MUC1 or were MUC1 null. All viruses demonstrated
      significant oncolytic abilities independent of MUC1 expression, although VSV
      DeltaM51-GFP was somewhat less effective in two PDA cell lines. In vivo
      administration of VSV-DeltaM51-GFP resulted in significant reduction of tumor
      growth for tested mouse PDA xenografts (+MUC1 or MUC1 null), and antitumor
      efficacy was further improved when the virus was combined with the
      chemotherapeutic drug gemcitabine. The antitumor effect was transient in all
      tested groups. The developed system can be used to study therapies involving
      various oncolytic viruses and chemotherapeutics, with the goal of inducing tumor
      specific immunity while preventing premature virus clearance. 

PMID- 23864626
TI  - The role of E3 in pH protection during alphavirus assembly and exit.
AB  - Alphaviruses are small enveloped viruses whose surface is covered by spikes
      composed of trimers of E2/E1 glycoprotein heterodimers. During virus entry, the
      E2/E1 dimer dissociates within the acidic endosomal environment, freeing the E1
      protein to mediate fusion of the viral and endosome membranes. E2 is synthesized
      as a precursor, p62, which is cleaved by furin in the late secretory pathway to
      produce mature E2 and a small peripheral glycoprotein, E3. The immature p62/E1
      dimer is acid resistant, but since p62 is cleaved before exit from the acidic
      secretory pathway, low pH-dependent binding of E3 to the spike complex is
      believed to prevent premature fusion. Based on analysis of the structure of the
      Chikungunya virus E3/E2/E1 complex, we hypothesized that interactions of E3
      residues Y47 and Y48 with E2 are important in this binding. We then directly
      tested the in vivo role of E3 in pH protection by alanine substitutions of E3 Y47
      and Y48 (Y47/48A) in Semliki Forest virus. The mutant was nonviable and was
      blocked in E1 transport to the plasma membrane and virus production. Although the
      Y47/48A mutant initially formed the p62/E1 heterodimer, the dimer dissociated
      during transport through the secretory pathway. Neutralization of the pH in the
      secretory pathway successfully rescued dimer association, E1 transport, and
      infectious particle production. Further mutagenesis identified the critical
      contact as the cation-pi interaction of E3 Y47 with E2. Thus, E3 mediates pH
      protection of E1 during virus biogenesis via interactions strongly dependent on
      Y47 at the E3-E2 interface. 

PMID- 23864627
TI  - Exosomes derived from Epstein-Barr virus-infected cells are internalized via
      caveola-dependent endocytosis and promote phenotypic modulation in target cells.
AB  - Epstein-Barr virus (EBV), a human gammaherpesvirus, establishes a lifelong latent
      infection in B lymphocytes and epithelial cells following primary infection.
      Several lines of evidence suggest that exosomes derived from EBV-infected cells
      are internalized and transfer viral factors, including EBV-encoded latent
      membrane protein and microRNAs, to the recipient cells. However, the detailed
      mechanism by which exosomes are internalized and their physiological impact on
      the recipient cells are still poorly understood. In this study, we visualized the
      internalization of fluorescently labeled exosomes derived from EBV-uninfected and
      EBV-infected B cells of type I and type III latency into EBV-negative epithelial
      cells. In this way, we demonstrated that exosomes derived from all three cell
      types were internalized into the target cells in a similar fashion.
      Internalization of exosomes was significantly suppressed by treatment with an
      inhibitor of dynamin and also by the knockdown of caveolin-1. Labeled exosomes
      were colocalized with caveolae and subsequently trafficked through endocytic
      pathways. Moreover, we observed that exosomes derived from type III latency cells
      upregulated proliferation and expression of intercellular adhesion molecule 1
      (ICAM-1) in the recipient cells more significantly than did those derived from
      EBV-negative and type I latency cells. We also identified the EBV latent membrane
      protein 1 (LMP1) gene as responsible for induction of ICAM-1 expression. Taken
      together, our data indicate that exosomes released from EBV-infected B cells are
      internalized via caveola-dependent endocytosis, which, in turn, contributes to
      phenotypic changes in the recipient cells through transferring one or more viral
      factors. 

PMID- 23864628
TI  - Phenotypic and functional characterization of circulating polyomavirus BK VP1
      specific CD8+ T cells in healthy adults.
AB  - The human polyomavirus BK virus (BKV) establishes a latent and asymptomatic
      infection in the majority of the population. In immunocompromised individuals,
      the virus frequently (re)activates and may cause severe disease such as
      interstitial nephritis and hemorrhagic cystitis. Currently, the therapeutic
      options are limited to reconstitution of the antiviral immune response. T cells
      are particularly important for controlling this virus, and T cell therapies may
      provide a highly specific and effective mode of treatment. However, little is
      known about the phenotype and function of BKV-specific T cells in healthy
      individuals. Using tetrameric BKV peptide-HLA-A02 complexes, we determined the
      presence, phenotype, and functional characteristics of circulating BKV VP1
      specific CD8(+) T cells in 5 healthy individuals. We show that these cells are
      present in low frequencies in the circulation and that they have a resting
      CD45RA(-) CD27(+) memory and predominantly CCR7(-) CD127(+) KLRG1(+) CD49d(hi)
      CXCR3(hi) T-bet(int) Eomesodermin(lo) phenotype. Furthermore, their direct
      cytotoxic capacity seems to be limited, since they do not readily express
      granzyme B and express only little granzyme K. We compared these cells to
      circulating CD8(+) T cells specific for cytomegalovirus (CMV), Epstein-Barr virus
      (EBV), and influenza virus (Flu) in the same donors and show that BKV-specific T
      cells have a phenotype that is distinct from that of CMV- and EBV-specific T
      cells. Lastly, we show that BKV-specific T cells are polyfunctional since they
      are able to rapidly express interleukin-2 (IL-2), gamma interferon (IFN-gamma),
      tumor necrosis factor alpha, and also, to a much lower extent, MIP-1beta and
      CD107a. 

PMID- 23864629
TI  - Hydrophobic and charged residues in the central segment of the measles virus
      hemagglutinin stalk mediate transmission of the fusion-triggering signal.
AB  - The pH-independent measles virus membrane fusion process begins when the
      attachment protein H binds to a receptor. Knowing that the central segment of the
      tetrameric H stalk transmits the signal to the fusion protein trimer, we
      investigated how. We document that exact conservation of most residues in the 92
      through 99 segment is essential for function. In addition, hydrophobic and
      charged residues in the 104 through 125 segment, arranged with helical
      periodicity, are critical for F protein interactions and signal transmission. 

PMID- 23864630
TI  - Targeting of human antigen-presenting cell subsets.
AB  - Antigen-presenting cells are a heterogeneous group of cells that are
      characterized by their functional specialization. Consequently, targeting
      specific antigen-presenting cell subsets offers opportunities to induce distinct
      T cell responses. Here we report on the generation and use of nanobodies (Nbs) to
      target lentivectors specifically to human lymph node-resident myeloid dendritic
      cells, demonstrating that Nbs represent a powerful tool to redirect lentivectors
      to human antigen-presenting cell subsets. 

PMID- 23864631
TI  - Fematrin-1 is involved in fetomaternal cell-to-cell fusion in Bovinae placenta
      and has contributed to diversity of ruminant placentation.
AB  - During placentation, mammals employ different strategies for nourishing and
      supporting fetuses. Members of the Bovidae family, consisting of cloven-hoofed
      ruminants, utilize multiple maternal attachment points on the placenta, known as
      cotyledons, and hybrid cells, named trinucleate cells or syncytial plaques, made
      up of a fusion of fetal trophoblasts and maternal endometrial cells to provide
      essential hormones and maintain long gestation periods. These hybrid cells are
      unique to the Bovidae, as fetomaternal borders are clearly separated by
      syncytiotrophoblasts or epithelial cells in the placenta of other mammals.
      Recently, it was reported that Syncytin-Rum1 was inserted into ruminant genomes,
      including cattle and sheep, and was possibly involved in fetomaternal cell-to
      cell fusion in both species. However, Syncytin-Rum1 alone is insufficient to
      explain the morphological diversity of the fetomaternal hybrids between Bovinae
      and Caprinae (i.e., trinucleate cells in Bovinae and syncytial plaques in
      Caprinae). Here we report that the bovine endogenous retrovirus K1 (BERV-K1)
      envelope, which we term Fematrin-1, was specifically expressed in binucleated
      trophoblasts throughout gestation in cattle and induced fusion with bovine
      endometrial cells in vitro at a significantly higher level than Syncytin-Rum1
      under physiological conditions. Fematrin-1 was found to be integrated into intron
      18 of FAT tumor suppressor homolog 2 (FAT2) about 18.3 to 25.4 million years ago
      and has been subject to purifying selection through the evolution of Bovinae.
      Phylogenetically, Fematrin-1 is distinct from Syncytin genes found in other
      mammalian species that form syncytiotrophoblasts. Our results suggest that the
      newly acquired endogenous retroelement has contributed to generating placentation
      diversity through ruminant evolution. 

PMID- 23864632
TI  - The C-terminal domain of chikungunya virus nsP2 independently governs viral RNA
      replication, cytopathicity, and inhibition of interferon signaling.
AB  - Alphavirus nonstructural protein 2 (nsP2) has pivotal roles in viral RNA
      replication, host cell shutoff, and inhibition of antiviral responses. Mutations
      that individually rendered other alphaviruses noncytopathic were introduced into
      chikungunya virus nsP2. Results show that (i) nsP2 mutation P718S only in
      combination with KR649AA or adaptive mutation D711G allowed noncytopathic
      replicon RNA replication, (ii) prohibiting nsP2 nuclear localization abrogates
      inhibition of antiviral interferon-induced JAK-STAT signaling, and (iii) nsP2
      independently affects RNA replication, cytopathicity, and JAK-STAT signaling. 

PMID- 23864633
TI  - Functional analysis of claudin-6 and claudin-9 as entry factors for hepatitis C
      virus infection of human hepatocytes by using monoclonal antibodies.
AB  - The relevance of claudin-6 and claudin-9 in hepatitis C virus (HCV) entry remains
      elusive. We produced claudin-6- or claudin-9-specific monoclonal antibodies that
      inhibit HCV entry into nonhepatic cells expressing exogenous claudin-6 or claudin
      9. These antibodies had no effect on HCV infection of hepatoma cells or primary
      hepatocytes. Thus, although claudin-6 and claudin-9 can serve as entry factors in
      cell lines, HCV infection into human hepatocytes is not dependent on claudin-6
      and claudin-9. 

PMID- 23864634
TI  - Virion factors that target Daxx to overcome intrinsic immunity.
AB  - PML nuclear bodies and their associated functions are part of an intrinsic
      cellular mechanism aimed at maintaining transcriptional control over viral gene
      expression and preventing replication of invading viruses. To overcome these
      barriers, many viruses express early nonstructural, multifunctional proteins to
      support the viral replication cycle or modulate host immune responses. Virion
      proteins constituting the invading particle are traditionally investigated for
      their role in transport during entry or egress and in the assembly of new
      virions. The additional functions of virion proteins have largely been ignored,
      in contrast to those of their nonstructural counterparts. A number of recent
      reports suggest that several virion proteins may also play vital roles in gene
      activation processes, in particular by counteracting intrinsic immune mechanisms
      mediated by the PML nuclear body-associated cellular factors Daxx, ATRX, and
      Sp100. These virion proteins share several features with their more potent
      nonstructural counterparts, and they may serve to bridge the gap in the early
      phase of an infection until immediate early viral gene expression is established.
      In this review, we discuss how virion proteins are an integral part of gene
      regulation among several viral families and to what extent structural proteins of
      incoming virions may contribute to species barrier, latency, and oncogenesis. 

PMID- 23864635
TI  - Dissection of the C-terminal region of E1A redefines the roles of CtBP and other
      cellular targets in oncogenic transformation.
AB  - Human adenovirus E1A makes extensive connections with the cellular protein
      interaction network. By doing so, E1A can manipulate many cellular programs,
      including cell cycle progression. Through these reprogramming events, E1A
      functions as a growth-promoting oncogene and has been used extensively to
      investigate mechanisms contributing to oncogenesis. Nevertheless, it remains
      unclear how the C-terminal region of E1A contributes to oncogenic transformation.
      Although this region is required for transformation in cooperation with E1B, it
      paradoxically suppresses transformation in cooperation with activated Ras.
      Previous analysis has suggested that the interaction of E1A with CtBP plays a
      pivotal role in both activities. However, some C-terminal mutants of E1A retain
      CtBP binding and yet exhibit defects in transformation, suggesting that other
      targets of this region are also necessary. To explore the roles of these
      additional factors, we performed an extensive mutational analysis of the C
      terminus of E1A. We identified key residues that are specifically required for
      binding all known targets of the C terminus of E1A. We further tested each mutant
      for the ability to both localize to the nucleus and transform primary rat cells
      in cooperation with E1B-55K or Ras. Interaction of E1A with importin alpha3/Qip1,
      dual-specificity tyrosine-regulated kinase 1A (DYRK1A), HAN11, and CtBP
      influenced transformation with E1B-55K. Interestingly, the interaction of E1A
      with DYRK1A and HAN11 appeared to play a role in suppression of transformation by
      activated Ras whereas interaction with CtBP was not necessary. This unexpected
      result suggests a need for revision of current models and provides new insight
      into transformation by the C terminus of E1A. 

PMID- 23864636
TI  - Magnetic fractionation and proteomic dissection of cellular organelles occupied
      by the late replication complexes of Semliki Forest virus.
AB  - Alphavirus replicase complexes are initially formed at the plasma membrane and
      are subsequently internalized by endocytosis. During the late stages of
      infection, viral replication organelles are represented by large cytopathic
      vacuoles, where replicase complexes bind to membranes of endolysosomal origin. In
      addition to viral components, these organelles harbor an unknown number of host
      proteins. In this study, a fraction of modified lysosomes carrying functionally
      intact replicase complexes was obtained by feeding Semliki Forest virus (SFV)
      infected HeLa cells with dextran-covered magnetic nanoparticles and later
      magnetically isolating the nanoparticle-containing lysosomes. Stable isotope
      labeling with amino acids in cell culture combined with quantitative proteomics
      was used to reveal 78 distinct cellular proteins that were at least 2.5-fold more
      abundant in replicase complex-carrying vesicles than in vesicles obtained from
      noninfected cells. These host components included the RNA-binding proteins PCBP1,
      hnRNP M, hnRNP C, and hnRNP K, which were shown to colocalize with the viral
      replicase. Silencing of hnRNP M and hnRNP C expression enhanced the replication
      of SFV, Chikungunya virus (CHIKV), and Sindbis virus (SINV). PCBP1 silencing
      decreased SFV-mediated protein synthesis, whereas hnRNP K silencing increased
      this synthesis. Notably, the effect of hnRNP K silencing on CHIKV- and SINV
      mediated protein synthesis was opposite to that observed for SFV. This study
      provides a new approach for analyzing the proteome of the virus replication
      organelle of positive-strand RNA viruses and helps to elucidate how host RNA
      binding proteins exert important but diverse functions during positive-strand RNA
      viral infection. 

PMID- 23864637
TI  - Rabbit anti-HIV-1 monoclonal antibodies raised by immunization can mimic the
      antigen-binding modes of antibodies derived from HIV-1-infected humans.
AB  - The rabbit is a commonly used animal model in studying antibody responses in
      HIV/AIDS vaccine development. However, no rabbit monoclonal antibodies (MAbs)
      have been developed previously to study the epitope-specific antibody responses
      against HIV-1 envelope (Env) glycoproteins, and little is known about how the
      rabbit immune system can mimic the human immune system in eliciting such
      antibodies. Here we present structural analyses of two rabbit MAbs, R56 and R20,
      against the third variable region (V3) of HIV-1 gp120. R56 recognizes the well
      studied immunogenic region in the V3 crown, while R20 targets a less-studied
      region at the C terminus of V3. By comparison of the Fab/epitope complex
      structures of these two antibodies raised by immunization with that of the
      corresponding human antibodies derived from patients chronically infected with
      HIV-1, we found that rabbit antibodies can recognize immunogenic regions of gp120
      and mimic the binding modes of human antibodies. This result can provide new
      insight into the use of the rabbit as an animal model in AIDS vaccine
      development. 

PMID- 23864638
TI  - Pressure from TRIM5alpha contributes to control of HIV-1 replication by
      individuals expressing protective HLA-B alleles.
AB  - The expression of certain HLA class I alleles, including HLA-B*27 and HLA-B*57,
      is associated with better control of human immunodeficiency virus type 1 (HIV-1)
      infection, but the mechanisms responsible are not fully understood. We sought
      evidence that pressure from the human restriction factor TRIM5alpha (hTRIM5alpha)
      could contribute to viral control. The hTRIM5alpha sensitivity of viruses from
      both HLA-B*57-positive (HLA-B*57(+)) and HLA-B*27(+) patients who spontaneously
      controlled viral replication, but not viruses from viremic patients expressing
      these alleles, was significantly greater than that of viruses from patients not
      expressing these protective HLA-B alleles. Overall, a significant negative
      correlation between hTRIM5alpha sensitivity and viral load was observed. In HLA
      B*57(+) patients, the T242N mutation in the HLA-B*57-restricted TW10 CD8(+) T
      lymphocyte (CTL) epitope was strongly associated with hTRIM5alpha sensitivity. In
      HLA-B*27(+) controllers, hTRIM5alpha sensitivity was associated with a
      significant reduction in emergence of key CTL mutations. In several patients,
      viral evolution to avoid hTRIM5alpha sensitivity was observed but could be
      associated with reduced viral replicative capacity. Thus, in individuals
      expressing protective HLA-B alleles, the combined pressures exerted by CTL,
      hTRIM5alpha, and capsid structural constraints can prevent viral escape both by
      impeding the selection of necessary resistance/compensatory mutations and forcing
      the selection of escape mutations that increase hTRIM5alpha sensitivity or impair
      viral replicative capacity. 

PMID- 23864639
TI  - The baculovirus core gene ac83 is required for nucleocapsid assembly and per os
      infectivity of Autographa californica nucleopolyhedrovirus.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac83 is a
      baculovirus core gene whose function in the AcMNPV life cycle is unknown. In the
      present study, an ac83-knockout AcMNPV (vAc83KO) was constructed to investigate
      the function of ac83 through homologous recombination in Escherichia coli. No
      budded virions were produced in vAc83KO-transfected Sf9 cells, although viral DNA
      replication was unaffected. Electron microscopy revealed that nucleocapsid
      assembly was aborted due to the ac83 deletion. Domain-mapping studies revealed
      that the expression of Ac83 amino acid residues 451 to 600 partially rescued the
      ability of AcMNPV to produce infectious budded virions. Bioassays indicated that
      deletion of the chitin-binding domain of Ac83 resulted in the failure of oral
      infection of Trichoplusia ni larvae by AcMNPV, but AcMNPV remained infectious
      following intrahemocoelic injection, suggesting that the domain is involved in
      the binding of occlusion-derived virions to the peritrophic membrane and/or to
      other chitin-containing insect tissues. It has been demonstrated that Ac83 is the
      only component with a chitin-binding domain in the per os infectivity factor
      complex on the occlusion-derived virion envelope. Interestingly, a functional
      inner nuclear membrane sorting motif, which may facilitate the localization of
      Ac83 to the envelopes of occlusion-derived virions, was identified by
      immunofluorescence analysis. Taken together, these results demonstrate that Ac83
      plays an important role in nucleocapsid assembly and the establishment of oral
      infection. 

PMID- 23864640
TI  - HLA-specific intracellular epitope processing shapes an immunodominance pattern
      for HLA-B*57 that is distinct from HLA-B*58:01.
AB  - HLA-B*57 is strongly associated with immune control of HIV and delayed AIDS
      progression. The closely related, but less protective, HLA-B*58:01 presents
      similar epitopes, but HLA-B*58:01(+) individuals do not generate CD8(+) T cells
      targeting the KF11-Gag epitope, which has been linked to low viremia. Here we
      show that HLA-B*58:01 binds and presents KF11 peptide, but HIV-infected HLA
      B*58:01(+) cells fail to process KF11. This unexpected finding demonstrates that
      immunodominance patterns can be influenced by intracellular events independent of
      HLA binding motifs. 

PMID- 23864641
TI  - Hypercapnia-induced increases in cerebral blood flow do not improve lower body
      negative pressure tolerance during hyperthermia.
AB  - Heat-related decreases in cerebral perfusion are partly the result of ventilatory
      related reductions in arterial CO2 tension. Cerebral perfusion likely contributes
      to an individual's tolerance to a challenge like lower body negative pressure
      (LBNP). Thus increasing cerebral perfusion may prolong LBNP tolerance. This study
      tested the hypothesis that a hypercapnia-induced increase in cerebral perfusion
      improves LBNP tolerance in hyperthermic individuals. Eleven individuals (31 +/- 7
      yr; 75 +/- 12 kg) underwent passive heat stress (increased intestinal temperature
      ~1.3 degrees C) followed by a progressive LBNP challenge to tolerance on two
      separate days (randomized). From 30 mmHg LBNP, subjects inhaled either (blinded)
      a hypercapnic gas mixture (5% CO2, 21% oxygen, balanced nitrogen) or room air
      (SHAM). LBNP tolerance was quantified via the cumulative stress index (CSI). Mean
      middle cerebral artery blood velocity (MCAvmean,) and end-tidal CO2 (PetCO2) were
      also measured. CO2 inhalation of 5% increased PetCO2 at ~40 mmHg LBNP (by 16 +/-
      4 mmHg) and at LBNP tolerance (by 18 +/- 5 mmHg) compared with SHAM (P < 0.01).
      Subsequently, MCAvmean was higher in the 5% CO2 trial during ~40 mmHg LBNP (by 21
      +/- 12 cm/s, ~31%) and at LBNP tolerance (by 18 +/- 10 cm/s, ~25%) relative to
      the SHAM (P < 0.01). However, hypercapnia-induced increases in MCAvmean did not
      alter LBNP tolerance (5% CO2 CSI: 339 +/- 155 mmHg * min; SHAM CSI: 273 +/- 158
      mmHg * min; P = 0.26). These data indicate that inhaling a hypercapnic gas
      mixture increases cerebral perfusion during LBNP but does not improve LBNP
      tolerance when hyperthermic. 

PMID- 23864642
TI  - Experimental estimates of peak skin dose and its relationship to the CT dose
      index using the CTDI head phantom.
AB  - A straightforward method is presented to estimate peak skin doses (PSDs)
      delivered by computed tomography (CT) scanners. The measured PSD values are
      related to the well-known volume CT dose index (CTDI(vol)), displayed on the
      console of CT scanners. PSD measurement estimates were obtained, in four CT
      units, by placing radiochromic film on the surface of a CTDI head phantom. Six
      different X-ray tube currents including the maximum allowed value were used to
      irradiate the phantom. PSD and CTDI(vol) were independently measured and later
      related to the CTDI(vol) value displayed on the console. A scanner-specific
      relationship was found between the measured PSD and the associated CTDI(vol)
      displayed on the console. The measured PSD values varied between 27 and 136 mGy
      among all scanners when the routine head scan parameters were used. The results
      of this work allow relating the widely used CTDI(vol) to an actual radiation dose
      delivered to the skin of a patient.

PMID- 23864643
TI  - Compliance boundaries for train protection systems.
AB  - Occupational exposure to non-ionising electromagnetic radiation emitted by train
      protection (TP) systems operating at ~27 MHz is investigated in situ. In total,
      five TP systems of two different types, i.e. KVB (Controle de Vitesse par
      Balises) and TBL1+ (Transmission Balise-Locomotive), are considered. For each
      type, the boundaries outside which the field levels are in compliance with the
      International Commission on Non-Ionizing Radiation Protection guidelines for
      occupational exposure ('compliance boundaries') are determined. Maximal fields of
      4.7 A m(-1) and 0.2 kV m(-1) for KVB, and 51 A m(-1) and 1.5 kV m(-1) for TBL1+
      are measured, at distances between 10 and 25 cm from the respective antennas.
      Compliance boundaries for occupational exposure are maximally 0.6 m for KVB to 1
      m for TBL1+, while no specific compliance boundary is needed for the general
      public. 

PMID- 23864644
TI  - Gamma photon techniques for detection of nucleation in superheated emulsion
      detectors for neutron dosimetry.
AB  - Application of transmission and scattering gamma photon techniques for
      calibration of superheated emulsion detectors used for neutron dosimetry is
      described. The bubbles nucleated in the detector due to neutron exposure generate
      detectable changes in both attenuation and scattering properties of the medium,
      and the magnitude of change in properties depends on population density of
      bubbles nucleated and in turn is proportional to neutron dose. The experimental
      set-up consists of (137)Cs and (241)Am sources and an HPGe detector-based gamma
      ray spectrometer. An indigenously developed bubble detector and a commercially
      available one (BTI, Canada) are used in the present study. Theoretical models for
      the variation in transmitted and scattered intensities through the bubble
      detector as a function of neutron dose are formulated, and the experimental
      results obtained are found to be in good agreement with the models. In the
      neutron dose region studied, the transmission technique shows better sensitivity
      than scattering technique. 

PMID- 23864646
TI  - Recognition errors suggest fast familiarity and slow recollection in rhesus
      monkeys.
AB  - One influential model of recognition posits two underlying memory processes:
      recollection, which is detailed but relatively slow, and familiarity, which is
      quick but lacks detail. Most of the evidence for this dual-process model in
      nonhumans has come from analyses of receiver operating characteristic (ROC)
      curves in rats, but whether ROC analyses can demonstrate dual processes has been
      repeatedly challenged. Here, we present independent converging evidence for the
      dual-process model from analyses of recognition errors made by rhesus monkeys.
      Recognition choices were made in three different ways depending on processing
      duration. Short-latency errors were disproportionately false alarms to familiar
      lures, suggesting control by familiarity. Medium-latency responses were less
      likely to be false alarms and were more accurate, suggesting onset of a
      recollective process that could correctly reject familiar lures. Long-latency
      responses were guesses. A response deadline increased false alarms, suggesting
      that limiting processing time weakened the contribution of recollection and
      strengthened the contribution of familiarity. Together, these findings suggest
      fast familiarity and slow recollection in monkeys, that monkeys use a "recollect
      to reject" strategy to countermand false familiarity, and that primate
      recognition performance is well-characterized by a dual-process model consisting
      of recollection and familiarity. 

PMID- 23864645
TI  - Mechanisms contributing to the induction and storage of Pavlovian fear memories
      in the lateral amygdala.
AB  - The relative contributions of plasticity in the amygdala vs. its afferent
      pathways to conditioned fear remain controversial. Some believe that thalamic and
      cortical neurons transmitting information about the conditioned stimulus (CS) to
      the lateral amygdala (LA) serve a relay function. Others maintain that thalamic
      and/or cortical plasticity is critically involved in fear conditioning. To
      address this question, we developed a large-scale biophysical model of the LA
      that could reproduce earlier findings regarding the cellular correlates of fear
      conditioning in LA. We then conducted model experiments that examined whether
      fear memories depend on (1) training-induced increases in the responsiveness of
      thalamic and cortical neurons projecting to LA, (2) plasticity at the synapses
      they form in LA, and/or (3) plasticity at synapses between LA neurons. These
      tests revealed that training-induced increases in the responsiveness of afferent
      neurons are required for fear memory formation. However, once the memory has been
      formed, this factor is no longer required because the efficacy of the synapses
      that thalamic and cortical neurons form with LA cells has augmented enough to
      maintain the memory. In contrast, our model experiments suggest that plasticity
      at synapses between LA neurons plays a minor role in maintaining the fear memory.

PMID- 23864647
TI  - Effect of 7 days of phenytoin on the pharmacokinetics of and the development of
      resistance to single-dose nevirapine for perinatal HIV prevention: a randomized
      pilot trial.
AB  - OBJECTIVES: To confirm whether 7 days of phenytoin, an enzyme inducer, would
      decrease the elimination half-life of single-dose nevirapine and to investigate
      its effect on the development of nevirapine resistance in pregnant, HIV-infected
      women. METHODS: In a pharmacokinetic pilot trial (NCT01187719), HIV-infected,
      antiretroviral (ARV)-naive pregnant women >=18 years old from Zambia and Tanzania
      and with CD4 cell counts >350 cells/mm(3) were randomized 1 : 1 to a control
      (zidovudine pre-delivery, single-dose nevirapine/zidovudine/lamivudine at
      delivery and zidovudine/lamivudine for 7 days post-delivery) or an intervention
      (control plus 184 mg of phenytoin once daily for 7 days post-delivery) group.
      Primary endpoints were the pharmacokinetics of and resistance to nevirapine.
      RESULTS: Thirty-five and 37 women were allocated to the control and intervention
      groups, with median (IQR) ages of 27 (23-31) and 27 (23-33) years, respectively.
      Twenty-three and 23 women had detectable nevirapine levels at delivery and
      subsequent samples in the control and the intervention groups, respectively.
      Geometric mean (GM) (95% CI) plasma levels of nevirapine at delivery were 1.02
      (0.58-1.78) mg/L and 1.14 (0.70-1.86) mg/L in the control and intervention
      groups, respectively (P = 0.76). One week after delivery, 0/23 (0%) and 15/22
      (68%) control and intervention mothers, respectively, had undetectable levels of
      nevirapine (<0.05 mg/L; P<0.001). One week later, the figures were 10/21 (48%)
      and 18/19 (95%) mothers, respectively (P = 0.002). The GM (95% CI) half-life of
      nevirapine was 63.2 (52.8-75.7) versus 25.5 (21.6-30.1) h in the control group
      versus the intervention group (P < 0.001). New nevirapine mutations were found in
      0/20 (0%) intervention-group mothers versus 1/21 (5%) control-group mothers.
      Overall, there was no difference in adverse events reported between the control
      and intervention arms (P > 0.28). CONCLUSIONS: Adding 7 days of an enzyme inducer
      to single-dose nevirapine to prevent mother-to-child transmission of HIV
      significantly reduced subtherapeutic nevirapine levels by shortening the half
      life of nevirapine. As prolonged subtherapeutic nevirapine dosage leads to the
      emergence of resistance, single-dose nevirapine could be used with phenytoin as
      an alternative if other ARVs were unavailable.

PMID- 23864648
TI  - Pseudomonas in augmented care: should we worry?
AB  - The problem of Pseudomonas as a nosocomial pathogen is not new, with some authors
      dating its onset to the start of the antimicrobial era, although other factors,
      such as the growth of intensive or augmented care, have a part to play. This
      paper outlines the historical and environmental issues that may be associated
      with a potential increase in the incidence of this difficult-to-treat pathogen. 

PMID- 23864649
TI  - Minireview: Signal bias, allosterism, and polymorphic variation at the GLP-1R:
      implications for drug discovery.
AB  - The glucagon-like peptide-1 receptor (GLP-1R) controls the physiological
      responses to the incretin hormone glucagon-like peptide-1 and is a major
      therapeutic target for the treatment of type 2 diabetes, owing to the broad range
      of effects that are mediated upon its activation. These include the promotion of
      glucose-dependent insulin secretion, increased insulin biosynthesis, preservation
      of beta-cell mass, improved peripheral insulin action, and promotion of weight
      loss. Regulation of GLP-1R function is complex, with multiple endogenous and
      exogenous peptides that interact with the receptor that result in the activation
      of numerous downstream signaling cascades. The current understanding of GLP-1R
      signaling and regulation is limited, with the desired spectrum of signaling
      required for the ideal therapeutic outcome still to be determined. In addition,
      there are several single-nucleotide polymorphisms (used in this review as
      defining a natural change of single nucleotide in the receptor sequence;
      clinically, this is viewed as a single-nucleotide polymorphism only if the
      frequency of the mutation occurs in 1% or more of the population) distributed
      within the coding sequence of the receptor protein that have the potential to
      produce differential responses for distinct ligands. In this review, we discuss
      the current understanding of GLP-1R function, in particular highlighting recent
      advances in the field on ligand-directed signal bias, allosteric modulation, and
      probe dependence and the implications of these behaviors for drug discovery and
      development. 

PMID- 23864650
TI  - Cyclin D1 determines estrogen signaling in the mammary gland in vivo.
AB  - The CCND1 gene, which is frequently overexpressed in cancers, encodes the
      regulatory subunit of a holoenzyme that phosphorylates the retinoblastoma
      protein. Although it is known that cyclin D1 regulates estrogen receptor
      (ER)alpha transactivation using heterologous reporter systems, the in vivo
      biological significance of cyclin D1 to estrogen-dependent signaling, and the
      molecular mechanisms by which cyclin D1 is involved, are yet to be elucidated.
      Herein, genome-wide expression profiling conducted of 17beta-estradiol-treated
      castrated virgin mice deleted of the Ccnd1 gene demonstrated that cyclin D1
      determines estrogen-dependent gene expression for 88% of estrogen-responsive
      genes in vivo. In addition, expression profiling of 17beta-estradiol-stimulated
      cyclin D1 small interfering RNA treated MCF7 cells shows cyclin D1 is required
      for estrogen-mediated gene expression in vitro. Genome-wide chromatin
      immunoprecipitation-Seq analysis revealed a cyclin D1-DNA bound form associated
      with genes that were regulated by estrogen in a cyclin D1-dependent manner. The
      cyclin D1-dependent estrogen signaling pathways identified in vivo were highly
      enriched for extracellular membrane-associated growth factor receptors (epidermal
      growth factor receptor, ErbB3, and EphB3) and their ligands (amphiregulin,
      encoded by AREG gene), and matrix metalloproteinase. The AREG protein, a pivotal
      ligand for epidermal growth factor receptors to promote cellular proliferation,
      was induced by cyclin D1 via the AREG promoter. Chromatin immunoprecipitation
      analysis demonstrated the recruitment of cyclin D1 to the breast cancer 1
      (Brca1)/ERalpha binding site of the Areg gene. Cyclin D1 genetic deletion
      demonstrated the in vivo requirement for cyclin D1 in assembling the estrogen
      dependent amplified in breast cancer 1-associated multiprotein complex. The
      current studies define a requirement for cyclin D1 in estrogen-dependent
      signaling modules governing growth factor receptor and ligand expression in vivo
      and reveal a noncanonical function of cyclin D1 at ERalpha target gene promoters.
      Cyclin D1 mediates the convergence of ERalpha and growth factor signaling at a
      common cis-element of growth factor genes. 

PMID- 23864651
TI  - The identification of novel proteins that interact with the GLP-1 receptor and
      restrain its activity.
AB  - Glucagon-like peptide 1 receptor (GLP-1R) controls diverse physiological
      functions in tissues including the pancreatic islets, brain, and heart. To
      understand the mechanisms that control glucagon-like peptide 1 (GLP-1) signaling
      better, we sought to identify proteins that interact with the GLP-1R using a
      membrane-based split ubiquitin yeast two-hybrid (MYTH) assay. A screen of a human
      fetal brain cDNA prey library with an unliganded human GLP-1R as bait in yeast
      revealed 38 novel interactor protein candidates. These interactions were
      confirmed in mammalian Chinese hamster ovarian cells by coimmunoprecipitation.
      Immunofluorescence was used to show subcellular colocalization of the interactors
      with GLP-1R. Cluster analysis revealed that the interactors were primarily
      associated with signal transduction, metabolism, and cell development. When
      coexpressed with the GLP-1R in Chinese hamster ovarian cells, 15 interactors
      significantly altered GLP-1-induced cAMP accumulation. Surprisingly, all 15
      proteins inhibited GLP-1-activated cAMP. Given GLP-1's prominent role as an
      incretin, we then focused on 3 novel interactors, SLC15A4, APLP1, and AP2M1,
      because they are highly expressed and localized to the membrane in mouse
      insulinoma beta-cells. Small interfering RNA-mediated knockdown of each candidate
      gene significantly enhanced GLP-1-induced insulin secretion. In conclusion, we
      have generated a novel GLP-1R-protein interactome, identifying several
      interactors that suppress GLP-1R signaling. We suggest that the inhibition of
      these interactors may serve as a novel strategy to enhance GLP-1R activity. 

PMID- 23864652
TI  - Role for human mediator subunit MED25 in recruitment of mediator to promoters by
      endoplasmic reticulum stress-responsive transcription factor ATF6alpha.
AB  - Transcription factor ATF6alpha functions as a master regulator of endoplasmic
      reticulum (ER) stress response genes. In response to ER stress, ATF6alpha
      translocates from its site of latency in the ER membrane to the nucleus, where it
      activates RNA polymerase II transcription of ER stress response genes upon
      binding sequence-specifically to ER stress response enhancer elements (ERSEs) in
      their promoter-regulatory regions. In a recent study, we demonstrated that
      ATF6alpha activates transcription of ER stress response genes by a mechanism
      involving recruitment to ERSEs of the multisubunit Mediator and several histone
      acetyltransferase (HAT) complexes, including Spt-Ada-Gcn5 (SAGA) and Ada-Two-A
      containing (ATAC) (Sela, D., Chen, L., Martin-Brown, S., Washburn, M.P., Florens,
      L., Conaway, J.W., and Conaway, R.C. (2012) J. Biol. Chem. 287, 23035-23045). In
      this study, we extend our investigation of the mechanism by which ATF6alpha
      supports recruitment of Mediator to ER stress response genes. We present findings
      arguing that Mediator subunit MED25 plays a critical role in this process and
      identify a MED25 domain that serves as a docking site on Mediator for the
      ATF6alpha transcription activation domain. 

PMID- 23864653
TI  - Molecular basis of glycosaminoglycan heparin binding to the chemokine CXCL1
      dimer.
AB  - Glycosaminoglycan (GAG)-bound and soluble chemokine gradients in the vasculature
      and extracellular matrix mediate neutrophil recruitment to the site of microbial
      infection and sterile injury in the host tissue. However, the molecular
      principles by which chemokine-GAG interactions orchestrate these gradients are
      poorly understood. This, in part, can be directly attributed to the complex
      interrelationship between the chemokine monomer-dimer equilibrium and binding
      geometry and affinities that are also intimately linked to GAG length. To address
      some of this missing knowledge, we have characterized the structural basis of
      heparin binding to the murine CXCL1 dimer. CXCL1 is a neutrophil-activating
      chemokine and exists as both monomers and dimers (Kd = 36 MUm). To avoid
      interference from monomer-GAG interactions, we designed a trapped dimer (dCXCL1)
      by introducing a disulfide bridge across the dimer interface. We characterized
      the binding of GAG heparin octasaccharide to dCXCL1 using solution NMR
      spectroscopy. Our studies show that octasaccharide binds orthogonally to the
      interhelical axis and spans the dimer interface and that heparin binding enhances
      the structural integrity of the C-terminal helical residues and stability of the
      dimer. We generated a quadruple mutant (H20A/K22A/K62A/K66A) on the basis of the
      binding data and observed that this mutant failed to bind heparin octasaccharide,
      validating our structural model. We propose that the stability enhancement of
      dimers upon GAG binding regulates in vivo neutrophil trafficking by increasing
      the lifetime of "active" chemokines, and that this structural knowledge could be
      exploited for designing inhibitors that disrupt chemokine-GAG interactions and
      neutrophil homing to the target tissue. 

PMID- 23864654
TI  - Quantification of mitochondrial acetylation dynamics highlights prominent sites
      of metabolic regulation.
AB  - Lysine acetylation is rapidly becoming established as a key post-translational
      modification for regulating mitochondrial metabolism. Nonetheless, distinguishing
      regulatory sites from among the thousands identified by mass spectrometry and
      elucidating how these modifications alter enzyme function remain primary
      challenges. Here, we performed multiplexed quantitative mass spectrometry to
      measure changes in the mouse liver mitochondrial acetylproteome in response to
      acute and chronic alterations in nutritional status, and integrated these data
      sets with our compendium of predicted Sirt3 targets. These analyses highlight a
      subset of mitochondrial proteins with dynamic acetylation sites, including acetyl
      CoA acetyltransferase 1 (Acat1), an enzyme central to multiple metabolic
      pathways. We performed in vitro biochemistry and molecular modeling to
      demonstrate that acetylation of Acat1 decreases its activity by disrupting the
      binding of coenzyme A. Collectively, our data reveal an important new target of
      regulatory acetylation and provide a foundation for investigating the role of
      select mitochondrial protein acetylation sites in mediating acute and chronic
      metabolic transitions. 

PMID- 23864655
TI  - Significance of glycosylphosphatidylinositol-anchored protein enrichment in lipid
      rafts for the control of autoimmunity.
AB  - Glycosylphosphatidylinositols (GPI) are complex glycolipids that are covalently
      linked to the C terminus of proteins as a post-translational modification and
      tether proteins to the plasma membrane. One of the most striking features of GPI
      anchored proteins (APs) is their enrichment in lipid rafts. The biosynthesis of
      GPI and its attachment to proteins occur in the endoplasmic reticulum. In the
      Golgi, GPI-APs are subjected to fatty acid remodeling, which replaces an
      unsaturated fatty acid at the sn-2 position of the phosphatidylinositol moiety
      with a saturated fatty acid. We previously reported that fatty acid remodeling is
      critical for the enrichment of GPI-APs in lipid rafts. To investigate the
      biological significance of GPI-AP enrichment in lipid rafts, we generated a PGAP3
      knock-out mouse (PGAP3(-/-)) in which fatty acid remodeling of GPI-APs does not
      occur. We report here that a significant number of aged PGAP3(-/-) mice developed
      autoimmune-like symptoms, such as increased anti-DNA antibodies, spontaneous
      germinal center formation, and enlarged renal glomeruli with deposition of immune
      complexes and matrix expansion. A possible cause for this was the impaired
      engulfment of apoptotic cells by resident peritoneal macrophages in PGAP3(-/-)
      mice. Mice with conditional targeting of PGAP3 in either B or T cells did not
      develop such autoimmune-like symptoms. In addition, PGAP3(-/-) mice exhibited the
      tendency of Th2 polarization. These data demonstrate that PGAP3-dependent fatty
      acid remodeling of GPI-APs has a significant role in the control of autoimmunity,
      possibly by the regulation of apoptotic cell clearance and Th1/Th2 balance. 

PMID- 23864656
TI  - Subunit delta is the key player for assembly of the H(+)-translocating unit of
      Escherichia coli F(O)F1 ATP synthase.
AB  - The ATP synthase (F(O)F1) of Escherichia coli couples the translocation of
      protons across the cytoplasmic membrane to the synthesis or hydrolysis of ATP.
      This nanomotor is composed of the rotor c10gammaepsilon and the stator
      ab2alpha3beta3delta. To study the assembly of this multimeric enzyme complex
      consisting of membrane-integral as well as peripheral hydrophilic subunits, we
      combined nearest neighbor analyses by intermolecular disulfide bond formation or
      purification of partially assembled F(O)F1 complexes by affinity chromatography
      with the use of mutants synthesizing different sets of F(O)F1 subunits. Together
      with a time-delayed in vivo assembly system, the results demonstrate that F(O)F1
      is assembled in a modular way via subcomplexes, thereby preventing the formation
      of a functional H(+)-translocating unit as intermediate product. Surprisingly,
      during the biogenesis of F(O)F1, F1 subunit delta is the key player in generating
      stable F(O). Subunit delta serves as clamp between ab2 and
      c10alpha3beta3gammaepsilon and guarantees that the open H(+) channel is
      concomitantly assembled within coupled F(O)F1 to maintain the low membrane proton
      permeability essential for viability, a general prerequisite for the assembly of
      multimeric H(+)-translocating enzymes.

PMID- 23864657
TI  - Tumor cell migration and invasion are enhanced by depletion of Rap1 GTPase
      activating protein (Rap1GAP).
AB  - The functional significance of the widespread down-regulation of Rap1 GTPase
      activating protein (Rap1GAP), a negative regulator of Rap activity, in human
      tumors is unknown. Here we show that human colon cancer cells depleted of Rap1GAP
      are endowed with more aggressive migratory and invasive properties. Silencing
      Rap1GAP enhanced the migration of confluent and single cells. In the latter,
      migration distance, velocity, and directionality were increased. Enhanced
      migration was a consequence of increased endogenous Rap activity as silencing Rap
      expression selectively abolished the migration of Rap1GAP-depleted cells. ROCK
      mediated cell contractility was suppressed in Rap1GAP-depleted cells, which
      exhibited a spindle-shaped morphology and abundant membrane protrusions. Tumor
      cells can switch between Rho/ROCK-mediated contractility-based migration and Rac1
      mediated mesenchymal motility. Strikingly, the migration of Rap1GAP-depleted, but
      not control cells required Rac1 activity, suggesting that loss of Rap1GAP alters
      migratory mechanisms. Inhibition of Rac1 activity restored membrane blebbing and
      increased ROCK activity in Rap1GAP-depleted cells, suggesting that Rac1
      contributes to the suppression of contractility. Collectively, these findings
      identify Rap1GAP as a critical regulator of aggressive tumor cell behavior and
      suggest that the level of Rap1GAP expression influences the migratory mechanisms
      that are operative in tumor cells. 

PMID- 23864658
TI  - Energy transducing roles of antiporter-like subunits in Escherichia coli NDH-1
      with main focus on subunit NuoN (ND2).
AB  - The proton-translocating NADH-quinone oxidoreductase (complex I/NDH-1) contains a
      peripheral and a membrane domain. Three antiporter-like subunits in the membrane
      domain, NuoL, NuoM, and NuoN (ND5, ND4 and ND2, respectively), are structurally
      similar. We analyzed the role of NuoN in Escherichia coli NDH-1. The lysine
      residue at position 395 in NuoN (NLys(395)) is conserved in NuoL (LLys(399)) but
      is replaced by glutamic acid (MGlu(407)) in NuoM. Our mutation study on NLys(395)
      suggests that this residue participates in the proton translocation. Furthermore,
      we found that MGlu(407) is also essential and most likely interacts with
      conserved LArg(175). Glutamic acids, NGlu(133), MGlu(144), and LGlu(144), are
      corresponding residues. Unlike mutants of MGlu(144) and LGlu(144), mutation of
      NGlu(133) scarcely affected the energy-transducing activities. However, a double
      mutant of NGlu(133) and nearby KGlu(72) showed significant inhibition of these
      activities. This suggests that NGlu(133) bears a functional role similar to
      LGlu(144) and MGlu(144) but its mutation can be partially compensated by the
      nearby carboxyl residue. Conserved prolines located at loops of discontinuous
      transmembrane helices of NuoL, NuoM, and NuoN were shown to play a similar role
      in the energy-transducing activity. It seems likely that NuoL, NuoM, and NuoN
      pump protons by a similar mechanism. Our data also revealed that NLys(158) is one
      of the key interaction points with helix HL in NuoL. A truncation study indicated
      that the C-terminal amphipathic segments of NTM14 interacts with the Mbeta sheet
      located on the opposite side of helix HL. Taken together, the mechanism of H(+)
      translocation in NDH-1 is discussed. 

PMID- 23864659
TI  - Obstruction of transmembrane helical movements in subunit a blocks proton pumping
      by F1Fo ATP synthase.
AB  - Subunit a plays a key role in promoting H(+) transport-coupled rotary motion of
      the subunit c ring in F1Fo ATP synthase. H(+) binding and release occur at Asp-61
      in the middle of the second transmembrane helix (TMH) of Fo subunit c. H(+) are
      thought to reach cAsp61 via aqueous half-channels formed by TMHs 2-5 of subunit
      a. Movements of TMH4 and TMH5 have been proposed to facilitate protonation of
      cAsp61 from a half channel centered in a four helix bundle at the periplasmic
      side of subunit a. The possible necessity of these proposed TMH movements was
      investigated by assaying ATP driven H(+) pumping function before and after cross
      linking paired Cys substitutions at the center of TMHs within subunit a. The
      cross-linking of the Cys pairs aG218C/I248C in TMH4 and TMH5, and aL120C/H245C in
      TMH2 and TMH5, inhibited H(+) pumping by 85-90%. H(+) pumping function was
      largely unaffected by modification of the same Cys residues in the absence of
      cross-link formation. The inhibition is consistent with the proposed requirement
      for TMH movements during the gating of periplasmic H(+) access to cAsp61. The
      cytoplasmic loops of subunit a have been implicated in gating H(+) release to the
      cytoplasm, and previous cross-linking experiments suggest that the chemically
      reactive regions of the loops may pack as a single domain. Here we show that Cys
      substitutions in these domains can be cross-linked with retention of function and
      conclude that these domains need not undergo large conformational changes during
      enzyme function. 

PMID- 23864660
TI  - Crystal structure of 3-hydroxybenzoate 6-hydroxylase uncovers lipid-assisted
      flavoprotein strategy for regioselective aromatic hydroxylation.
AB  - 3-Hydroxybenzoate 6-hydroxylase (3HB6H) from Rhodococcus jostii RHA1 is a dimeric
      flavoprotein that catalyzes the NADH- and oxygen-dependent para-hydroxylation of
      3-hydroxybenzoate to 2,5-dihydroxybenzoate. In this study, we report the crystal
      structure of 3HB6H as expressed in Escherichia coli. The overall fold of 3HB6H is
      similar to that of p-hydroxybenzoate hydroxylase and other flavoprotein aromatic
      hydroxylases. Unexpectedly, a lipid ligand is bound to each 3HB6H monomer. Mass
      spectral analysis identified the ligand as a mixture of phosphatidylglycerol and
      phosphatidylethanolamine. The fatty acid chains occupy hydrophobic channels that
      deeply penetrate into the interior of the substrate-binding domain of each
      subunit, whereas the hydrophilic part is exposed on the protein surface,
      connecting the dimerization domains via a few interactions. Most remarkably, the
      terminal part of a phospholipid acyl chain is directly involved in the substrate
      binding site. Co-crystallized chloride ion and the crystal structure of the H213S
      variant with bound 3-hydroxybenzoate provide hints about oxygen activation and
      substrate hydroxylation. Essential roles are played by His-213 in catalysis and
      Tyr-105 in substrate binding. This phospholipid-assisted strategy to control
      regioselective aromatic hydroxylation is of relevance for optimization of flavin
      dependent biocatalysts. 

PMID- 23864661
TI  - Inhibition of DNA binding of MCM2-7 complex by phosphorylation with cyclin
      dependent kinases.
AB  - Cyclin-dependent kinase (CDK) that plays a central role in preventing re
      replication of DNA phosphorylates several replication proteins to inactivate
      them. MCM4 in MCM2-7 and RPA2 in RPA are phosphorylated with CDK in vivo. There
      are inversed correlations between the phosphorylation of these proteins and their
      chromatin binding. Here, we examined in vitro phosphorylation of human
      replication proteins of MCM2-7, RPA, TRESLIN, CDC45 and RECQL4 with CDK2/cyclinE,
      CDK2/cyclinA, CDK1/cyclinB, CHK1, CHK2 and CDC7/DBF4 kinases. MCM4, RPA2, TRESLIN
      and RECQL4 were phosphorylated with CDKs. Effect of the phosphorylation by
      CDK2/cyclinA on DNA-binding abilities of MCM2-7 and RPA was examined by gel-shift
      analysis. The phosphorylation of RPA did not affect its DNA-binding ability but
      that of MCM4 inhibited the ability of MCM2-7. Change of six amino acids of serine
      and threonine to alanines in the amino-terminal region of MCM4 rendered the
      mutant MCM2-7 insensitive to the inhibition with CDK. These biochemical data
      suggest that phosphorylation of MCM4 at these sites by CDK plays a direct role in
      dislodging MCM2-7 from chromatin and/or preventing re-loading of the complex to
      chromatin. 

PMID- 23864662
TI  - Cone phosphodiesterase-6alpha' restores rod function and confers distinct
      physiological properties in the rod phosphodiesterase-6beta-deficient rd10 mouse.
AB  - Phosphodiesterase-6 (PDE6) is the key effector enzyme of the vertebrate
      phototransduction pathway in rods and cones. Rod PDE6 catalytic core is composed
      of two distinct subunits, PDE6alpha and PDE6beta, whereas two identical
      PDE6alpha' subunits form the cone PDE6 catalytic core. It is not known whether
      this difference in PDE6 catalytic subunit identity contributes to the functional
      differences between rods and cones. To address this question, we expressed cone
      PDE6alpha' in the photoreceptor cells of the retinal degeneration 10 (rd10) mouse
      that carries a mutation in rod PDEbeta subunit. We show that adeno-associated
      virus-mediated subretinal delivery of PDE6alpha' rescues rod electroretinogram
      responses and preserves retinal structure, indicating that cone PDE6alpha' can
      couple effectively to the rod phototransduction pathway. We also show that
      restoration of light sensitivity in rd10 rods is attributable to assembly of
      PDE6alpha' with rod PDE6gamma. Single-cell recordings revealed that,
      surprisingly, rods expressing cone PDE6alpha' are twofold more sensitive to light
      than wild-type rods, most likely because of the slower shutoff of their light
      responses. Unlike in wild-type rods, the response kinetics in PDE6alpha'-treated
      rd10 rods accelerated with increasing flash intensity, indicating a possible
      direct feedback modulation of cone PDE6alpha' activity. Together, these results
      demonstrate that cone PDE6alpha' can functionally substitute for rod PDEalphabeta
      in vivo, conferring treated rods with distinct physiological properties. 

PMID- 23864663
TI  - Neural signatures of test-potentiated learning in parietal cortex.
AB  - Testing, or retrieval practice, is beneficial for long-term memory both directly,
      by enhancing performance on tested information, and indirectly, by facilitating
      learning from subsequent encounters with the information. Although a wealth of
      behavioral research has examined the "testing effect," neuroimaging has provided
      little insight regarding the potential mechanisms that underlie the benefits of
      retrieval practice. Here, fMRI was used to examine the effects of retrieval
      practice on later study trials. Human subjects studied pairs of associated words,
      which were then tested, restudied, or neither tested nor restudied. All pairs
      were then studied once more in expectation of a final test. We asked how this
      Final Study episode was affected by prior history (whether the pair had been
      previously tested, restudied, or neither). The data revealed striking
      similarities between responses in lateral parietal cortex in the present study
      and those in a host of studies explicitly tapping recognition memory processes.
      Moreover, activity in lateral parietal cortex during Final Study was correlated
      with a behavioral index of test-potentiated learning. We conclude that retrieval
      practice may enhance learning by promoting the recruitment of retrieval
      mechanisms during subsequent study opportunities. 

PMID- 23864664
TI  - Persistent synaptic scaling independent of AMPA receptor subunit composition.
AB  - Despite long-standing evidence that the specific intracellular domains of AMPA
      type glutamate receptor (AMPAR) subunits are critical for trafficking, it has
      recently been demonstrated that there is no absolute requirement for any AMPAR
      subunit for the receptor insertion underlying LTP. It is unclear whether this
      holds true to other forms of plasticity. Homeostatic synaptic plasticity (HSP) is
      an important form of negative feedback that provides stability to neuronal
      networks, and results at least in part from the insertion of AMPARs into
      glutamatergic synapses following chronic reductions in neuronal activity. Similar
      to LTP, the GluA1 subunit has been suggested to be the requisite subunit for HSP
      induced AMPAR insertion and acute treatment with signaling molecules that
      underlie some forms of HSP results in the preferential incorporation of GluA2
      lacking receptors. However, knockdown experiments have instead implicated a
      requirement for the GluA2 subunit. Here we re-examined the requirement for
      specific AMPAR subunit during chronic tetrodotoxin-induced HSP using hippocampal
      cultures derived from AMPAR subunit knock-out mice. We observed HSP in cultures
      from GluA1-/-, GluA2-/-, and GluA2-/- GluA3-/- mice, and conclude that, as with
      LTP, there is no subunit requirement for HSP.

PMID- 23864665
TI  - Faces in motion: selectivity of macaque and human face processing areas for
      dynamic stimuli.
AB  - Face recognition mechanisms need to extract information from static and dynamic
      faces. It has been hypothesized that the analysis of dynamic face attributes is
      performed by different face areas than the analysis of static facial attributes.
      To date, there is no evidence for such a division of labor in macaque monkeys. We
      used fMRI to determine specializations of macaque face areas for motion. Face
      areas in the fundus of the superior temporal sulcus responded to general object
      motion; face areas outside of the superior temporal sulcus fundus responded more
      to facial motion than general object motion. Thus, the macaque face-processing
      system exhibits regional specialization for facial motion. Human face areas,
      processing the same stimuli, exhibited specializations for facial motion as well.
      Yet the spatial patterns of facial motion selectivity differed across species,
      suggesting that facial dynamics are analyzed differently in humans and macaques. 

PMID- 23864666
TI  - Temporally coherent visual stimuli boost ocular dominance plasticity.
AB  - Does cortical plasticity depend on the temporal coherence of visual stimuli? We
      addressed this question by studying ocular dominance (OD) plasticity in mice that
      were stimulated by moving square wave gratings for 6 h/d during a period of
      monocular deprivation (MD). It turned out that 4 d of deprivation were sufficient
      to induce a saturated shift in plasticity in adult (older than postnatal day 100)
      mice. Seeking to determine the shortest effective period of stimulation, we
      further showed that even 2 d of deprivation and stimulation shifted OD at any
      age. This shift was achieved by a decline in deprived-eye input that was
      saturated within 2 d and did not change during 7 d of MD. However, after 2 weeks
      of MD, cortical activity induced by both eyes increased again and this increase
      did not depend on continued stimulation, suggesting a homeostatic mechanism.
      Starting stimulation 4 d before MD did not mask OD plasticity, showing that the
      effect is not merely due to the "stimulus-dependent response potentiation"
      described recently (Frenkel et al., 2006). These results are the first to
      demonstrate the influence of stimulus quality on cortical plasticity and that
      cortical responses can be changed within very short periods of time (merely 2 d).

PMID- 23864667
TI  - Efference copy failure during smooth pursuit eye movements in schizophrenia.
AB  - Abnormal smooth pursuit eye movements in patients with schizophrenia are often
      considered a consequence of impaired motion perception. Here we used a novel
      motion prediction task to assess the effects of abnormal pursuit on perception in
      human patients. Schizophrenia patients (n = 15) and healthy controls (n = 16)
      judged whether a briefly presented moving target ("ball") would hit/miss a
      stationary vertical line segment ("goal"). To relate prediction performance and
      pursuit directly, we manipulated eye movements: in half of the trials, observers
      smoothly tracked the ball; in the other half, they fixated on the goal. Strict
      quality criteria ensured that pursuit was initiated and that fixation was
      maintained. Controls were significantly better in trajectory prediction during
      pursuit than during fixation, their performance increased with presentation
      duration, and their pursuit gain and perceptual judgments were correlated. Such
      perceptual benefits during pursuit may be due to the use of extraretinal motion
      information estimated from an efference copy signal. With an overall lower
      performance in pursuit and perception, patients showed no such pursuit advantage
      and no correlation between pursuit gain and perception. Although patients'
      pursuit showed normal improvement with longer duration, their prediction
      performance failed to benefit from duration increases. This dissociation
      indicates relatively intact early visual motion processing, but a failure to use
      efference copy information. Impaired efference function in the sensory system may
      represent a general deficit in schizophrenia and thus contribute to symptoms and
      functional outcome impairments associated with the disorder. 

PMID- 23864668
TI  - Gait abnormalities and progressive myelin degeneration in a new murine model of
      Pelizaeus-Merzbacher disease with tandem genomic duplication.
AB  - Pelizaeus-Merzbacher disease (PMD) is a hypomyelinating leukodystrophy caused by
      mutations of the proteolipid protein 1 gene (PLP1), which is located on the X
      chromosome and encodes the most abundant protein of myelin in the central nervous
      sytem. Approximately 60% of PMD cases result from genomic duplications of a
      region of the X chromosome that includes the entire PLP1 gene. The duplications
      are typically in a head-to-tail arrangement, and they vary in size and gene
      content. Although rodent models with extra copies of Plp1 have been developed,
      none contains an actual genomic rearrangement that resembles those found in PMD
      patients. We used mutagenic insertion chromosome engineering resources to
      generate the Plp1dup mouse model by introducing an X chromosome duplication in
      the mouse genome that contains Plp1 and five neighboring genes that are also
      commonly duplicated in PMD patients. The Plp1dup mice display progressive gait
      abnormalities compared with wild-type littermates. The single duplication leads
      to increased transcript levels of Plp1 and four of the five other duplicated
      genes over wild-type levels in the brain beginning the second postnatal week. The
      Plp1dup mice also display altered transcript levels of other important myelin
      proteins leading to a progressive degeneration of myelin. Our results show that a
      single duplication of the Plp1 gene leads to a phenotype similar to the pattern
      seen in human PMD patients with duplications. 

PMID- 23864669
TI  - Corticosterone acts in the nucleus accumbens to enhance dopamine signaling and
      potentiate reinstatement of cocaine seeking.
AB  - Stressful life events are important contributors to relapse in recovering cocaine
      addicts, but the mechanisms by which they influence motivational systems are
      poorly understood. Studies suggest that stress may "set the stage" for relapse by
      increasing the sensitivity of brain reward circuits to drug-associated stimuli.
      We examined the effects of stress and corticosterone on behavioral and
      neurochemical responses of rats to a cocaine prime after cocaine self
      administration and extinction. Exposure of rats to acute electric footshock
      stress did not by itself reinstate drug-seeking behavior but potentiated
      reinstatement in response to a subthreshold dose of cocaine. This effect of
      stress was not observed in adrenalectomized animals, and was reproduced in
      nonstressed animals by administration of corticosterone at a dose that reproduced
      stress-induced plasma levels. Pretreatment with the glucocorticoid receptor
      antagonist RU38486 did not block the corticosterone effect. Corticosterone
      potentiated cocaine-induced increases in extracellular dopamine in the nucleus
      accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked
      corticosterone-induced potentiation of reinstatement. Intra-accumbens
      administration of corticosterone reproduced the behavioral effects of stress and
      systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine
      clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of
      uptake2-mediated dopamine clearance may underlie corticosterone effects.
      Consistent with this hypothesis, intra-accumbens administration of the uptake2
      inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression
      of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter,
      was detected on NAc neurons. These findings reveal a novel mechanism by which
      stress hormones can rapidly regulate dopamine signaling and contribute to the
      impact of stress on drug intake.

PMID- 23864670
TI  - Cytoskeletal determinants of stimulus-response habits.
AB  - Both humans and rodents can learn to associate specific actions with their
      outcomes, but with repeated performance or exposure to pathological stimuli, such
      as drugs of abuse, behaviors assume stimulus-elicited, or "habitual," qualities.
      Psychostimulants remodel dorsal striatal neurons, critical determinants of
      decision-making strategies, but cytoskeletal mechanisms associated with drug
      induced habit formation are largely unknown. We first show that cocaine can bias
      decision-making strategies toward stimulus-response habits by interfering with
      learning about the predictive relationship between a response and its outcome. In
      the dorsomedial, but not ventral, striatum, cocaine decreases PSD95 expression
      and phosphorylation of cortactin, a cytoskeletal regulator that interacts with,
      and is phophorylated by, the Abl2 (Arg) kinase. Based on this pattern, we
      inhibited Abl-family kinase signaling in the dorsomedial striatum, impairing new
      response-outcome learning. Consistent with evidence that the dorsomedial striatum
      promotes response-outcome decision-making while the dorsolateral compartment
      promotes stimulus-response habits, inhibition of Abl-family kinases in the
      dorsolateral striatum reinstates goal sensitivity in over-trained "habitual"
      mice. These findings provide a structural mechanism by which even acute exposure
      to drugs of abuse can reorganize behavioral response strategies and promote
      outcome-insensitive stimulus-response habits. 

PMID- 23864671
TI  - Effect of prestimulus alpha power, phase, and synchronization on stimulus
      detection rates in a biophysical attractor network model.
AB  - Spontaneous oscillations measured by local field potentials,
      electroencephalograms and magnetoencephalograms exhibit a pronounced peak in the
      alpha band (8-12 Hz) in humans and primates. Both instantaneous power and phase
      of these ongoing oscillations have commonly been observed to correlate with
      psychophysical performance in stimulus detection tasks. We use a novel model
      based approach to study the effect of prestimulus oscillations on detection rate.
      A previously developed biophysically detailed attractor network exhibits
      spontaneous oscillations in the alpha range before a stimulus is presented and
      transiently switches to gamma-like oscillations on successful detection. We
      demonstrate that both phase and power of the ongoing alpha oscillations modulate
      the probability of such state transitions. The power can either positively or
      negatively correlate with the detection rate, in agreement with experimental
      findings, depending on the underlying neural mechanism modulating the oscillatory
      power. Furthermore, the spatially distributed alpha oscillators of the network
      can be synchronized by global nonspecific weak excitatory signals. These
      synchronization events lead to transient increases in alpha-band power and render
      the network sensitive to the exact timing of target stimuli, making the alpha
      cycle function as a temporal mask in line with recent experimental observations.
      Our results are relevant to several studies that attribute a modulatory role to
      prestimulus alpha dynamics. 

PMID- 23864672
TI  - Norepinephrine enhances a discrete form of long-term depression during fear
      memory storage.
AB  - Amygdala excitatory synaptic strengthening is thought to contribute to both
      conditioned fear and anxiety. Thus, one basis for behavioral flexibility could
      allow these pathways to be weakened and corresponding emotion to be attenuated.
      However, synaptic depression within the context of amygdala-dependent behavior
      remains poorly understood. Previous work identified lateral amygdala (LA) calcium
      permeable AMPA receptors (CP-AMPARs) as a key target for synaptic removal in long
      term depression (LTD) and persistent fear attenuation. Here we demonstrate that
      LA neurons express two equally potent forms of LTD with contrasting requirements
      for protein kinase and phosphatase activity and differential impact on CP-AMPAR
      trafficking. Selective removal of CP-AMPARs from synapses is contingent on group
      1 metabotropic glutamate receptor (mGluR1) and PKC signaling, in contrast to an
      alternate LTD pathway that nonselectively removes AMPARs and requires calcineurin
      (PP2b). Intriguingly, the balance between these forms of LTD is shifted by
      posttraining activation of beta-adrenergic receptors in fear conditioned mice,
      resulting in selective augmentation of mGluR-dependent depression. These results
      highlight the complexity of core mechanisms in LTD and suggest that
      norepinephrine exposure mediates a form of synaptic metaplasticity that
      recalibrates fear memory processing. 

PMID- 23864673
TI  - Disassociation of histone deacetylase-3 from normal huntingtin underlies mutant
      huntingtin neurotoxicity.
AB  - Huntington's disease (HD) is caused by a polyglutamine expansion within the
      huntingtin (Htt) protein. Both loss of function of normal Htt and gain of a toxic
      function by the polyglutamine-expanded mutant Htt protein have been proposed to
      be responsible for HD, although the molecular mechanisms involved are unclear. We
      show that Htt is a neuroprotective protein in both HD-related and unrelated model
      systems. Neuroprotection by Htt is mediated by its sequestration of histone
      deacetylase-3 (HDAC3), a protein known to promote neuronal death. In contrast to
      the normal Htt, mutant Htt interacts poorly with HDAC3. However, expression of
      mutant Htt liberates HDAC3 from Htt, thus de-repressing its neurotoxic activity.
      Indeed, mutant Htt neurotoxicity is inhibited by the knockdown of HDAC3 and
      markedly reduced in HDAC3-deficient neurons. A reduction in Htt-HDAC3 interaction
      is also seen in neurons exposed to other apoptotic stimuli and in the striatum of
      R6/2 HD mice. Our results suggest that the robust interaction between Htt and
      HDAC3 along with the ability of mutant Htt to disrupt this association while not
      itself interacting with HDAC3 provides an explanation for both the loss-of
      function and gain-of-toxic-function mechanisms proposed for HD. Moreover, our
      results identify HDAC3 as an essential player in mutant Htt-induced
      neurodegeneration. 

PMID- 23864674
TI  - Conserved chromosome 2q31 conformations are associated with transcriptional
      regulation of GAD1 GABA synthesis enzyme and altered in prefrontal cortex of
      subjects with schizophrenia.
AB  - Little is known about chromosomal loopings involving proximal promoter and distal
      enhancer elements regulating GABAergic gene expression, including changes in
      schizophrenia and other psychiatric conditions linked to altered inhibition.
      Here, we map in human chromosome 2q31 the 3D configuration of 200 kb of linear
      sequence encompassing the GAD1 GABA synthesis enzyme gene locus, and we describe
      a loop formation involving the GAD1 transcription start site and intergenic
      noncoding DNA elements facilitating reporter gene expression. The GAD1-TSS(
      50kbLoop) was enriched with nucleosomes epigenetically decorated with the
      transcriptional mark, histone H3 trimethylated at lysine 4, and was weak or
      absent in skin fibroblasts and pluripotent stem cells compared with neuronal
      cultures differentiated from them. In the prefrontal cortex of subjects with
      schizophrenia, GAD1-TSS(-50kbLoop) was decreased compared with controls, in
      conjunction with downregulated GAD1 expression. We generated transgenic mice
      expressing Gad2 promoter-driven green fluorescent protein-conjugated histone H2B
      and confirmed that Gad1-TSS(-55kbLoop), the murine homolog to GAD1-TSS(
      50kbLoop), is a chromosomal conformation specific for GABAergic neurons. In
      primary neuronal culture, Gad1-TSS(-55kbLoop) and Gad1 expression became
      upregulated when neuronal activity was increased. We conclude that 3D genome
      architectures, including chromosomal loopings for promoter-enhancer interactions
      involved in the regulation of GABAergic gene expression, are conserved between
      the rodent and primate brain, and subject to developmental and activity-dependent
      regulation, and disordered in some cases with schizophrenia. More broadly, the
      findings presented here draw a connection between noncoding DNA, spatial genome
      architecture, and neuronal plasticity in development and disease. 

PMID- 23864676
TI  - Spectrum of short- and long-term brain pathology and long-term behavioral
      deficits in male repeated hypoxic rats closely resembling human extreme
      prematurity.
AB  - Brain injury in the premature infant is associated with a high risk of
      neurodevelopmental disability. Previous small-animal models of brain injury
      attributable to extreme prematurity typically fail to generate a spectrum of
      pathology and behavior that closely resembles that observed in humans, although
      they provide initial answers to numerous cellular, molecular, and therapeutic
      questions. We tested the hypothesis that exposure of rats to repeated hypoxia
      from postnatal day 1 (P1) to P3 models the characteristic white matter
      neuropathological injury, gray matter volume loss, and memory deficits seen in
      children born extremely prematurely. Male Sprague Dawley rats were exposed to
      repeated hypoxia or repeated normoxia from P1 to P3. The absolute number of pre
      oligodendrocytes and mature oligodendrocytes, the surface area and g-ratio of
      myelin, the absolute volume of cerebral white and gray matter, and the absolute
      number of cerebral neurons were quantified stereologically. Spatial memory was
      investigated on a radial arm maze. Rats exposed to repeated hypoxia had a
      significant loss of (1) pre-oligodendrocytes at P4, (2) cerebral white matter
      volume and myelin at P14, (3) cerebral cortical and striatal gray matter volume
      without neuronal loss at P14, and (4) cerebral myelin and memory deficits in
      adulthood. Decreased myelin was correlated with increased attention deficit
      hyperactivity disorder-like hyperactivity. This new small-animal model of extreme
      prematurity generates a spectrum of short- and long-term pathology and behavior
      that closely resembles that observed in humans. This new rat model provides a
      clinically relevant tool to investigate numerous cellular, molecular, and
      therapeutic questions on brain injury attributable to extreme prematurity. 

PMID- 23864675
TI  - Choosing the rules: distinct and overlapping frontoparietal representations of
      task rules for perceptual decisions.
AB  - Behavior is governed by rules that associate stimuli with responses and outcomes.
      Human and monkey studies have shown that rule-specific information is widely
      represented in the frontoparietal cortex. However, it is not known how
      establishing a rule under different contexts affects its neural representation.
      Here, we use event-related functional MRI (fMRI) and multivoxel pattern
      classification methods to investigate the human brain's mechanisms of
      establishing and maintaining rules for multiple perceptual decision tasks. Rules
      were either chosen by participants or specifically instructed to them, and the
      fMRI activation patterns representing rule-specific information were compared
      between these contexts. We show that frontoparietal regions differ in the
      properties of their rule representations during active maintenance before
      execution. First, rule-specific information maintained in the dorsolateral and
      medial frontal cortex depends on the context in which it was established (chosen
      vs specified). Second, rule representations maintained in the ventrolateral
      frontal and parietal cortex are independent of the context in which they were
      established. Furthermore, we found that the rule-specific coding maintained in
      anticipation of stimuli may change with execution of the rule: representations in
      context-independent regions remain invariant from maintenance to execution
      stages, whereas rule representations in context-dependent regions do not
      generalize to execution stage. The identification of distinct frontoparietal
      systems with context-independent and context-dependent task rule representations,
      and the distinction between anticipatory and executive rule representations,
      provide new insights into the functional architecture of goal-directed behavior. 

PMID- 23864677
TI  - Subjective rating of weak tactile stimuli is parametrically encoded in event
      related potentials.
AB  - Neural signatures of somatosensory awareness have often been studied by examining
      EEG responses to hardly detectable stimuli. Previous reports consistently showed
      that event-related potentials (ERPs) measured over early somatosensory cortex
      diverge for detected and missed perithreshold stimuli at 80-100 ms after stimulus
      onset. So far, however, all previous studies have operationalized somatosensory
      awareness as binary stimulus detection. Here, we investigated whether ERP
      components attributed to neuronal activity in early somatosensory cortices would
      parametrically reflect subjective ratings of stimulus awareness. EEG (64 channel)
      was recorded in human participants (N = 20), with perithreshold electrical
      stimulation applied to the left median nerve. Participants indicated
      perceptibility on a continuous visual rating scale, and stimulation intensity was
      readjusted in each block to a perithreshold level. The aim of the analysis was to
      investigate which brain areas reflect the subsequent perceptual awareness ratings
      parametrically, and how early such parametric effects occur. Parametric ERP
      effects were found as early as 86 ms after stimulus onset. This parametric
      modulation of ERP amplitude was source localized to secondary somatosensory
      cortex, and attributed to feedforward processing between primary and secondary
      somatosensory cortex by means of dynamic causal modeling (DCM). Furthermore,
      later in the analysis window, the subjective rating of stimuli correlated with
      the amplitude of the N140 component and with a broadly distributed P300
      component. By DCM modeling, these late effects were explained in terms of
      recurrent processing within the network of somatosensory and premotor cortices.
      Our results indicate that early neural activity in the somatosensory cortex can
      reflect the subjective quality of tactile perception. 

PMID- 23864678
TI  - Processing of natural sounds: characterization of multipeak spectral tuning in
      human auditory cortex.
AB  - We examine the mechanisms by which the human auditory cortex processes the
      frequency content of natural sounds. Through mathematical modeling of ultra-high
      field (7 T) functional magnetic resonance imaging responses to natural sounds, we
      derive frequency-tuning curves of cortical neuronal populations. With a data
      driven analysis, we divide the auditory cortex into five spatially distributed
      clusters, each characterized by a spectral tuning profile. Beyond neuronal
      populations with simple single-peaked spectral tuning (grouped into two
      clusters), we observe that ~60% of auditory populations are sensitive to multiple
      frequency bands. Specifically, we observe sensitivity to multiple frequency bands
      (1) at exactly one octave distance from each other, (2) at multiple harmonically
      related frequency intervals, and (3) with no apparent relationship to each other.
      We propose that beyond the well known cortical tonotopic organization,
      multipeaked spectral tuning amplifies selected combinations of frequency bands.
      Such selective amplification might serve to detect behaviorally relevant and
      complex sound features, aid in segregating auditory scenes, and explain prominent
      perceptual phenomena such as octave invariance. 

PMID- 23864679
TI  - Effects of adult neural precursor-derived myelination on axonal function in the
      perinatal congenitally dysmyelinated brain: optimizing time of intervention,
      developing accurate prediction models, and enhancing performance.
AB  - Stem cell repair shows substantial translational potential for neurological
      injury, but the mechanisms of action remain unclear. This study aimed to
      investigate whether transplanted stem cells could induce comprehensive functional
      remyelination. Subventricular zone (SVZ)-derived adult neural precursor cells
      (aNPCs) were injected bilaterally into major cerebral white matter tracts of
      myelin-deficient shiverer mice on postnatal day (P) 0, P7, and P21. Tripotential
      NPCs, when transplanted in vivo, integrated anatomically and functionally into
      local white matter and preferentially became Olig2+, Myelin Associated
      Glycoprotein-positive, Myelin Basic Protein-positive oligodendrocytes, rather
      than Glial Fibrillary Acidic Protein-positive astrocytes or Neurofiliment 200
      positive neurons. Processes interacted with axons and transmission electron
      microscopy showed multilamellar axonal ensheathment. Nodal architecture was
      restored and by quantifying these anatomical parameters a computer model was
      generated that accurately predicted action potential velocity, determined by ex
      vivo slice recordings. Although there was no obvious phenotypic improvement in
      transplanted shi/shis, myelinated axons exhibited faster conduction, lower
      activation threshold, less refractoriness, and improved response to high
      frequency stimulation than dysmyelinated counterparts. Furthermore, they showed
      improved resilience to ischemic insult, a promising finding in the context of
      perinatal brain injury. This study describes, for the first time mechanistically,
      the functional characteristics and anatomical integration of nonimmortalized
      donor SVZ-derived murine aNPCs in the dysmyelinated brain at key developmental
      time points. 

PMID- 23864681
TI  - Shootin1 acts in concert with KIF20B to promote polarization of migrating
      neurons.
AB  - Shootin1 has been ascribed a role in regulating polarization of primary
      hippocampal neurons. To better understand the possible role of Shootin1 in the
      developing brain, we identified a member of the kinesin superfamily, KIF20B, as a
      novel Shootin1 interacting protein and a potential mediator of Shootin1
      interaction with microtubules. KIF20B/Shootin1 binding was mapped to a 57 aa
      KIF20B sequence, which was used as a dominant-negative fragment. Direct
      interaction between that peptide (MBD) and Shootin1 was confirmed by surface
      plasmon resonance-based technology and the affinity was determined in the 10-7 m
      range. The proteins are expressed in the developing brain and formed a complex in
      vivo based on coimmunoprecipitation experiments and coimmunostaining in primary
      neurons. In primary hippocampal neurons Kif20b knockdown reduced Shootin1
      mobilization to the developing axon, as evidenced by immunostaining and
      fluorescence recovery after photobleaching analysis, suggesting that Shootin1 is
      a novel KIF20B cargo. shRNA targeting of Shootin1 reduced PIP3 accumulation in
      the growth cone, as did Kif20b shRNA. In the developing mouse brain, Kif20b
      knockdown or expression of the KIF20B minimal binding domain inhibited neuronal
      migration, and in vivo migration assays suggested that Shootin1/Kif20b acts in
      the same genetic pathway. Time-lapse imaging of multipolar cells in the
      subventricular zone revealed that downregulating levels of either Shootin1 or
      Kif20b hindered the transition from multipolar to bipolar cells. Collectively,
      our data demonstrate the importance of the Shootin1/KIF20B interaction to the
      dynamic process of pyramidal neuronal polarization and migration.

PMID- 23864680
TI  - The Drosophila transcription factor Adf-1 (nalyot) regulates dendrite growth by
      controlling FasII and Staufen expression downstream of CaMKII and neural
      activity.
AB  - Memory deficits in Drosophila nalyot mutants suggest that the Myb family
      transcription factor Adf-1 is an important regulator of developmental plasticity
      in the brain. However, the cellular functions for this transcription factor in
      neurons or molecular mechanisms by which it regulates plasticity remain unknown.
      Here, we use in vivo 3D reconstruction of identifiable larval motor neuron
      dendrites to show that Adf-1 is required cell autonomously for dendritic
      development and activity-dependent plasticity of motor neurons downstream of
      CaMKII. Adf-1 inhibition reduces dendrite growth and neuronal excitability, and
      results in motor deficits and altered transcriptional profiles. Surprisingly,
      analysis by comparative chromatin immunoprecipitation followed by sequencing
      (ChIP-Seq) of Adf-1, RNA Polymerase II (Pol II), and histone modifications in Kc
      cells shows that Adf-1 binding correlates positively with high Pol II-pausing
      indices and negatively with active chromatin marks such as H3K4me3 and H3K27ac.
      Consistently, the expression of Adf-1 targets Staufen and Fasciclin II (FasII),
      identified through larval brain ChIP-Seq for Adf-1, is negatively regulated by
      Adf-1, and manipulations of these genes predictably modify dendrite growth. Our
      results imply mechanistic interactions between transcriptional and local
      translational machinery in neurons as well as conserved neuronal growth
      mechanisms mediated by cell adhesion molecules, and suggest that CaMKII, Adf-1,
      FasII, and Staufen influence crucial aspects of dendrite development and
      plasticity with potential implications for memory formation. Further, our
      experiments reveal molecular details underlying transcriptional regulation by Adf
      1, and indicate active interaction between Adf-1 and epigenetic regulators of
      gene expression during activity-dependent neuronal plasticity. 

PMID- 23864682
TI  - NGL-2 regulates pathway-specific neurite growth and lamination, synapse
      formation, and signal transmission in the retina.
AB  - Parallel processing is an organizing principle of many neural circuits. In the
      retina, parallel neuronal pathways process signals from rod and cone
      photoreceptors and support vision over a wide range of light levels. Toward this
      end, rods and cones form triad synapses with dendrites of distinct bipolar cell
      types, and the axons or dendrites, respectively, of horizontal cells (HCs). The
      molecular cues that promote the formation of specific neuronal pathways remain
      largely unknown. Here, we discover that developing and mature HCs express the
      leucine-rich repeat (LRR)-containing protein netrin-G ligand 2 (NGL-2). NGL-2
      localizes selectively to the tips of HC axons, which form reciprocal connections
      with rods. In mice with null mutations in Ngl-2 (Ngl-2-/-), many branches of HC
      axons fail to stratify in the outer plexiform layer (OPL) and invade the outer
      nuclear layer. In addition, HC axons expand lateral territories and increase
      coverage of the OPL, but establish fewer synapses with rods. NGL-2 can form
      transsynaptic adhesion complexes with netrin-G2, which we show to be expressed by
      photoreceptors. In Ngl-2-/- mice, we find specific defects in the assembly of
      presynaptic ribbons in rods, indicating that reverse signaling of complexes
      involving NGL-2 regulates presynaptic maturation. The development of HC dendrites
      and triad synapses of cone photoreceptors proceeds normally in the absence of NGL
      2 and in vivo electrophysiology reveals selective defects in rod-mediated signal
      transmission in Ngl-2-/- mice. Thus, our results identify NGL-2 as a central
      component of pathway-specific development in the outer retina.

PMID- 23864683
TI  - D1 dopamine receptor-mediated LTP at GABA synapses encodes motivation to self
      administer cocaine in rats.
AB  - Enhanced motivation to take drugs is a central characteristic of addiction, yet
      the neural underpinning of this maladaptive behavior is still largely unknown.
      Here, we report a D1-like dopamine receptor (DRD1)-mediated long-term
      potentiation of GABAA-IPSCs (D1-LTPGABA) in the oval bed nucleus of the stria
      terminalis that was positively correlated with motivation to self-administer
      cocaine in rats. Likewise, in vivo intra-oval bed nucleus of the stria terminalis
      DRD1 pharmacological blockade reduced lever pressing for cocaine more effectively
      in rats showing enhanced motivation toward cocaine. D1-LTPGABA resulted from
      enhanced function and expression of G-protein-independent DRD1 coupled to c-Src
      tyrosine kinases and required local release of neurotensin. There was no D1
      LTPGABA in rats that self-administered sucrose, in those with limited cocaine
      self-administration experience, or in those that received cocaine passively
      (yoked). Therefore, our study reveals a novel neurophysiological mechanism
      contributing to individual motivation to self-administer cocaine, a critical
      psychobiological element of compulsive drug use and addiction. 

PMID- 23864685
TI  - Gait disorders in parkinsonian monkeys with pedunculopontine nucleus lesions: a
      tale of two systems.
AB  - Gait and balance disorders unresponsive to dopaminergic drugs in Parkinson's
      disease (PD) are secondary to lesions located outside the dopaminergic system.
      However, available animal models of PD fail to display l-3,4
      dihydroxyphenylalanine (DOPA)-responsive parkinsonism and drug-resistant gait and
      balance disorders, and this lack of appropriate model could account for the
      deficit of efficient treatments. Because the pedunculopontine nucleus (PPN) plays
      an important role in locomotion control, we conducted the present study to
      investigate the consequences of combined dopaminergic and PPN lesions in a same
      animal. We used macaques that received first 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) intoxication to render them parkinsonian and then local
      stereotaxic lesion of the PPN. Adding bilateral PPN lesions in MPTP-lesioned
      macaques induced dopamine-resistant gait and balance disorders but unexpectedly
      improved hypokinesia. Additional MPTP injections resulted in the association of a
      severe DOPA-responsive parkinsonism together with DOPA-unresponsive gait
      disorders. Histological examination assessed a severe dopaminergic degeneration
      and a significant loss of PPN cholinergic neurons. We observed similar results in
      aged monkeys intoxicated with MPTP: they developed severe DOPA-responsive
      hypokinesia and tremor together with unresponsive gait and balance disorders and
      displayed dopaminergic lesion and a weak but significant cholinergic PPN lesion.
      Our results highlight the complex role of the cholinergic PPN neurons in the
      pathophysiology of PD because its lesion induces a dual effect with an
      improvement of hypokinesia contrasting with a worsening of DOPA-unresponsive gait
      and balance disorders. Thus, we obtained a primate model of PD that could be
      useful to test symptomatic treatments for these heavily disabling symptoms. 

PMID- 23864684
TI  - Coordinated regulation of hepatic energy stores by leptin and hypothalamic agouti
      related protein.
AB  - Like obesity, prolonged food deprivation induces severe hepatic steatosis;
      however, the functional significance of this phenomenon is not well understood.
      In this study, we show that the fall in plasma leptin concentration during
      fasting is required for the development of hepatic steatosis in mice. Removal of
      leptin receptors from AGRP neurons diminishes fasting-induced hepatic steatosis.
      Furthermore, the suppressive effects of leptin on fasting-induced hepatic
      steatosis are absent in mice lacking the gene encoding agouti-related protein
      (Agrp), suggesting that this function of leptin is mediated by AGRP. Prolonged
      fasting leads to suppression of hepatic sympathetic activity, increased
      expression of acyl CoA:diacylglycerol acyltransferase-2 in the liver, and
      elevation of hepatic triglyceride content and all of these effects are blunted in
      the absence of AGRP. AGRP deficiency, despite having no effects on feeding or
      body adiposity in the free-fed state, impairs triglyceride and ketone body
      release from the liver during prolonged fasting. Furthermore, reducing CNS Agrp
      expression in wild-type mice by RNAi protected against the development of hepatic
      steatosis not only during starvation, but also in response to consumption of a
      high-fat diet. These findings identify the leptin-AGRP circuit as a critical
      modulator of hepatic triglyceride stores in starvation and suggest a vital role
      for this circuit in sustaining the supply of energy from the liver to
      extrahepatic tissues during periods of prolonged food deprivation. 

PMID- 23864686
TI  - Patients with chronic visceral pain show sex-related alterations in intrinsic
      oscillations of the resting brain.
AB  - Abnormal responses of the brain to delivered and expected aversive gut stimuli
      have been implicated in the pathophysiology of irritable bowel syndrome (IBS), a
      visceral pain syndrome occurring more commonly in women. Task-free resting-state
      functional magnetic resonance imaging (fMRI) can provide information about the
      dynamics of brain activity that may be involved in altered processing and/or
      modulation of visceral afferent signals. Fractional amplitude of low-frequency
      fluctuation is a measure of the power spectrum intensity of spontaneous brain
      oscillations. This approach was used here to identify differences in the resting
      state activity of the human brain in IBS subjects compared with healthy controls
      (HCs) and to identify the role of sex-related differences. We found that both the
      female HCs and female IBS subjects had a frequency power distribution skewed
      toward high frequency to a greater extent in the amygdala and hippocampus
      compared with male subjects. In addition, female IBS subjects had a frequency
      power distribution skewed toward high frequency in the insula and toward low
      frequency in the sensorimotor cortex to a greater extent than male IBS subjects.
      Correlations were observed between resting-state blood oxygen level-dependent
      signal dynamics and some clinical symptom measures (e.g., abdominal discomfort).
      These findings provide the first insight into sex-related differences in IBS
      subjects compared with HCs using resting-state fMRI. 

PMID- 23864687
TI  - Low-dimensional sensory feature representation by trigeminal primary afferents.
AB  - In any sensory system, the primary afferents constitute the first level of
      sensory representation and fundamentally constrain all subsequent information
      processing. Here, we show that the spike timing, reliability, and stimulus
      selectivity of primary afferents in the whisker system can be accurately
      described by a simple model consisting of linear stimulus filtering combined with
      spike feedback. We fitted the parameters of the model by recording the responses
      of primary afferents to filtered, white noise whisker motion in anesthetized
      rats. The model accurately predicted not only the response of primary afferents
      to white noise whisker motion (median correlation coefficient 0.92) but also to
      naturalistic, texture-induced whisker motion. The model accounted both for
      submillisecond spike-timing precision and for non-Poisson spike train structure.
      We found substantial diversity in the responses of the afferent population, but
      this diversity was accurately captured by the model: a 2D filter subspace,
      corresponding to different mixtures of position and velocity sensitivity,
      captured 94% of the variance in the stimulus selectivity. Our results suggest
      that the first stage of the whisker system can be well approximated as a bank of
      linear filters, forming an overcomplete representation of a low-dimensional
      feature space. 

PMID- 23864689
TI  - Expression of the gamma2-subunit distinguishes synaptic and extrasynaptic GABA(A)
      receptors in NG2 cells of the hippocampus.
AB  - NG2 cells are equipped with transmitter receptors and receive direct synaptic
      input from glutamatergic and GABAergic neurons. The functional impact of these
      neuron-glia synapses is still unclear. Here, we combined functional and molecular
      techniques to analyze properties of GABA(A) receptors in NG2 cells of the
      juvenile mouse hippocampus. GABA activated slowly desensitizing responses in NG2
      cells, which were mimicked by muscimol and inhibited by bicuculline. To elucidate
      the subunit composition of the receptors we tested its pharmacological
      properties. Coapplication of pentobarbital, benzodiazepines, and zolpidem all
      significantly increased the GABA-evoked responses. The presence of small tonic
      currents indicated the presence of extrasynaptic GABA(A) receptors. To further
      analyze the subunit expression, single cell transcript analysis was performed
      subsequent to functional characterization of NG2 cells. The subunits alpha1,
      alpha2, beta3, gamma1, and gamma2 were most abundantly expressed, matching
      properties resulting from pharmacological characterization. Importantly, lack of
      the gamma2-subunit conferred a high Zn2+ sensitivity to the GABA(A) receptors of
      NG2 cells. Judging from the zolpidem sensitivity, postsynaptic GABA(A) receptors
      in NG2 cells contain the gamma2-subunit, in contrast to extrasynaptic receptors,
      which were not modulated by zolpidem. To determine the effect of GABA(A) receptor
      activation on membrane potential, perforated patch recordings were obtained from
      NG2 cells. In the current-clamp mode, GABA depolarized the cells to approximately
      -30 mV, indicating a higher intracellular Cl- concentration (~50 mM) than
      previously reported. GABA-induced depolarization in NG2 cells might trigger Ca2+
      influx through voltage-activated Ca2+ channels.

PMID- 23864688
TI  - Motor circuit-specific burst patterns drive different muscle and behavior
      patterns.
AB  - In the isolated CNS, different modulatory inputs can enable one motor network to
      generate multiple output patterns. Thus far, however, few studies have
      established whether different modulatory inputs also enable a defined network to
      drive distinct muscle and movement patterns in vivo, much as they enable these
      distinctions in behavioral studies. This possibility is not a foregone
      conclusion, because additional influences present in vivo (e.g., sensory
      feedback, hormonal modulation) could alter the motor patterns. Additionally,
      rhythmic neuronal activity can be transformed into sustained muscle contractions,
      particularly in systems with slow muscle dynamics, as in the crab (Cancer
      borealis) stomatogastric system used here. We assessed whether two different
      versions of the biphasic (protraction, retraction) gastric mill (chewing) rhythm,
      triggered in the isolated stomatogastric system by the modulatory ventral cardiac
      neurons (VCNs) and postoesophageal commissure (POC) neurons, drive different
      muscle and movement patterns. One distinction between these rhythms is that the
      lateral gastric (LG) protractor motor neuron generates tonic bursts during the
      VCN rhythm, whereas its POC-rhythm bursts are divided into fast, rhythmic
      burstlets. Intracellular muscle fiber recordings and tension measurements show
      that the LG-innervated muscles retain the distinct VCN-LG and POC-LG neuron burst
      structures. Moreover, endoscope video recordings in vivo, during VCN-triggered
      and POC-triggered chewing, show that the lateral teeth protraction movements
      exhibit the same, distinct protraction patterns generated by LG in the isolated
      nervous system. Thus, the multifunctional nature of an identified motor network
      in the isolated CNS can be preserved in vivo, where it drives different muscle
      activity and movement patterns. 

PMID- 23864690
TI  - Toll-like receptor-3 activation increases the vulnerability of the neonatal brain
      to hypoxia-ischemia.
AB  - Susceptibility and progression of brain injury in the newborn is closely
      associated with an exacerbated innate immune response, but the underlying
      mechanisms are often unclear. Toll-like receptors (TLRs) are important innate
      immune sensors that may influence the vulnerability of the developing brain. In
      the current study, we provide novel data to show that activation of the viral
      innate immune receptor TLR-3 sensitizes the neonatal brain to subsequent hypoxic
      ischemic (HI) damage. Poly inosinic:poly cytidylic acid (Poly I:C), a synthetic
      ligand for TLR-3, was administered to neonatal mice 14 h before cerebral HI.
      Activation of TLR-3 before HI increased infarct volume from 3.0 +/- 0.5 to 15.4
      +/- 2.1 mm3 and augmented loss of myelin basic protein from 13.4 +/- 6.0 to 70.6
      +/- 5.3%. The sensitizing effect of Poly I:C was specific for the TLR-3 pathway
      because mice deficient in the TLR-3 adaptor protein Toll/IL-1R domain-containing
      adaptor molecule-1 (TRIF) did not develop larger brain damage. The increased
      vulnerability was associated with a TRIF-dependent heightened inflammatory
      response, including proinflammatory cytokines, chemokines, and the apoptosis
      associated mediator Fas, whereas there was a decrease in reparative M2-like
      CD11b+ microglia and phosphorylation of Akt. Because TLR-3 is activated via
      double-stranded RNA during most viral infections, the present study provides
      evidence that viral infections during pregnancy or in the neonate could have
      great impact on subsequent HI brain injury.

PMID- 23864691
TI  - Asynchronous movements prior to pore opening in NMDA receptors.
AB  - Glutamate-gated ion channels embedded within the neuronal membrane are the
      primary mediators of fast excitatory synaptic transmission in the CNS. The ion
      channel of these glutamate receptors contains a pore-lining transmembrane M3
      helix surrounded by peripheral M1 and M4 helices. In the NMDA receptor subtype,
      opening of the ion channel pore, mediated by displacement of the M3 helices away
      from the central pore axis, occurs in a highly concerted fashion, but the
      associated temporal movements of the peripheral helices are unknown. To address
      the gating dynamics of the peripheral helices, we constrained the relative
      movements of the linkers that connect these helices to the ligand-binding domain
      using engineered cross-links, either within (intra-GluN1 or GluN2A) or between
      subunits. Constraining the peripheral linkers in any manner dramatically
      curtailed channel opening, highlighting the requirement for rearrangements of
      these peripheral structural elements for efficient gating to occur. However, the
      magnitude of this gating effect depended on the specific subunit being
      constrained, with the most dramatic effects occurring when the constraint was
      between subunits. Based on kinetic and thermodynamic analysis, our results
      suggest an asynchrony in the displacement of the peripheral linkers during the
      conformational and energetic changes leading to pore opening. Initially there are
      large-scale rearrangements occurring between the four subunits. Subsequently,
      rearrangements occur within individual subunits, mainly GluN2A, leading up to or
      in concert with pore opening. Thus, the conformational changes induced by agonist
      binding in NMDA receptors converge asynchronously to permit pore opening. 

PMID- 23864692
TI  - CASK regulates SAP97 conformation and its interactions with AMPA and NMDA
      receptors.
AB  - SAP97 interacts with AMPA receptors (AMPARs) and NMDA receptors (NMDARs) during
      sorting and trafficking to synapses. Here we addressed how SAP97 distinguishes
      between AMPARs and NMDARs and what role the adaptor/scaffold protein, CASK, plays
      in the process. Using intramolecular SAP97 Forster resonance energy transfer
      sensors, we demonstrated that SAP97 is in "extended" or "compact" conformations
      in vivo. SAP97 conformation was regulated by a direct interaction between SAP97
      and CASK through L27 protein-interaction domains on each protein. Unbound SAP97
      was mostly in the compact conformation, while CASK binding stabilized it in an
      extended conformation. In HEK cells and rat hippocampal neurons, SAP97 in the
      compact conformation preferentially associated and colocalized with GluA1
      containing AMPARs, and in the extended conformation colocalized with GluN2B
      containing NMDARs. Altogether, our findings suggest a molecular mechanism by
      which CASK binding regulates SAP97 conformation and its subsequent sorting and
      synaptic targeting of AMPARs and NMDARs during trafficking to synapses. 

PMID- 23864693
TI  - Saccade target selection relies on feedback competitive signal integration.
AB  - It is often assumed that decision making involves neural competition,
      accumulation of evidence "scores" over time, and commitment to a particular
      alternative once its scores reach a critical decision threshold first. So far,
      however, neither the first-to-threshold rule nor the nature of competition
      (feedforward or feedback inhibition) has been revealed by experiments. Here, we
      presented two simultaneously flashed targets that reversed their intensity
      difference during each presentation and instructed human subjects to make a
      saccade toward the brightest target. All subjects preferentially chose the target
      that was brightest during the first stimulus phase. Unless this first phase
      lasted only 40 ms, this primacy effect persisted even if the second, reversed
      intensity phase lasted longer. This effect did not result from premature
      commitment to the initially dominant target, because a strong target imbalance in
      the opposite direction later drove nearly all responses toward that location.
      Moreover, there was a nonmonotonic relation between target imbalance and primacy:
      increasing the target imbalance beyond 40 cd/m(2) caused an attenuation of
      primacy. These are the hallmarks of hysteresis, predicted by models in which
      target representations compete through strong feedback. Reaction times were
      independent of the choice probability. This dissociation suggests that target
      selection and movement initiation are distinct phenomena. 

PMID- 23864694
TI  - Vowel category boundaries enhance cortical and behavioral responses to speech
      feedback alterations.
AB  - Auditory feedback is instrumental in the online control of speech, allowing
      speakers to compare their self-produced speech signal with a desired auditory
      target and correct for errors. However, there is little account of the
      representation of "target" and "error": does error depend purely on acoustic
      distance from a target, or is error enhanced by phoneme category changes? Here,
      we show an effect of vowel boundaries on compensatory responses to a real-time
      auditory perturbation. While human subjects spoke monosyllabic words, event
      triggered functional magnetic resonance imaging was used to characterize neural
      responses to unexpected changes in auditory feedback. Capitalizing on speakers'
      natural variability, we contrasted the responses to feedback perturbations
      applied to two classes of utterances: (1) those that fell nearer to the category
      boundary, for which perturbations were designed to change the phonemic identity
      of the heard speech; and (2) those that fell farther from the boundary, for which
      perturbations resulted in only sub-phonemic auditory differences. Subjects'
      behavioral compensation was more than three times greater when feedback shifts
      were applied nearer to a category boundary. Furthermore, a near-boundary shift
      resulted in stronger cortical responses, most notably in right posterior superior
      temporal gyrus, than an identical shift that occurred far from the boundary.
      Across participants, a correlation was found between the amount of compensation
      to the perturbation and the amount of activity in a network of superior temporal
      and inferior frontal brain regions. Together, these results demonstrate that
      auditory feedback control of speech is sensitive to linguistic categories learned
      through auditory experience. 

PMID- 23864695
TI  - Rho-kinase accelerates synaptic vesicle endocytosis by linking cyclic GMP
      dependent protein kinase activity to phosphatidylinositol-4,5-bisphosphate
      synthesis.
AB  - Rho-kinase plays diverse roles in cell motility. During neuronal development, Rho
      kinase is involved in neuronal migration, and in neurite outgrowth and
      retraction. Rho-kinase remains highly expressed in mature neurons, but its
      physiological roles are poorly understood. Here we report that Rho-kinase plays a
      key role in the synaptic vesicle recycling system in presynaptic terminals.
      Vesicles consumed by excessive exocytosis are replenished by accelerating vesicle
      endocytosis via a retrograde feedback mechanism involving nitric oxide released
      from postsynaptic cells. This homeostatic control system involves presynaptic
      cyclic GMP-dependent protein kinase (PKG) and a plasma membrane phospholipid,
      phosphatidylinositol-4,5-bisphophate (PIP2). We found that application of a Rho
      kinase inhibitor, a PKG inhibitor or both, reduced the PIP2 content in Wistar rat
      brainstem synaptosomes to a similar extent. Likewise, application of the Rho
      kinase inhibitor into the calyx of Held presynaptic terminal slowed vesicle
      endocytosis to the same degree as did application of the PKG inhibitor. This
      endocytic slowing effect of the Rho-kinase inhibitor was canceled by
      coapplication of PIP2 into the terminal. By contrast, a RhoA activator increased
      the PIP2 content and reversed the effect of the PKG inhibitor in brainstem
      synaptosomes. The RhoA activator, when loaded into calyceal terminals, also
      rescued the endocytic slowing effect of the PKG inhibitor. Furthermore,
      intraterminal loading of anti-PIP2 antibody slowed vesicle endocytosis and
      blocked the rescuing effect of the RhoA activator. We conclude that Rho-kinase
      links presynaptic PKG activity to PIP2 synthesis, thereby controlling the
      homeostatic balance of vesicle exocytosis and endocytosis in nerve terminals. 

PMID- 23864696
TI  - Interleukin-1beta alters glutamate transmission at purkinje cell synapses in a
      mouse model of multiple sclerosis.
AB  - Cerebellar deficit contributes significantly to disability in multiple sclerosis
      (MS). Several clinical and experimental studies have investigated the
      pathophysiology of cerebellar dysfunction in this neuroinflammatory disorder, but
      the cellular and molecular mechanisms are still unclear. In experimental
      autoimmune encephalomyelitis (EAE), a mouse model of MS, proinflammatory
      cytokines, together with a degeneration of inhibitory neurons, contribute to
      impair GABAergic transmission at Purkinje cells (PCs). Here, we investigated
      glutamatergic transmission to gain insight into the pathophysiology of cerebellar
      dysfunction in EAE. Electrophysiological recordings from PCs showed increased
      duration of spontaneous excitatory postsynaptic currents (EPSCs) during the
      symptomatic phase of EAE, suggesting an alteration of glutamate uptake played by
      Bergmann glia. We indeed observed an impaired functioning of the glutamate
      aspartate transporter/excitatory amino acid transporter 1 (GLAST/EAAT1) in EAE
      cerebellum caused by protein downregulation and in correlation with prominent
      astroglia activation. We have also demonstrated that the proinflammatory cytokine
      interleukin-1beta (IL-1beta), released by a subset of activated
      microglia/macrophages and infiltrating lymphocytes, was involved directly in such
      synaptic alteration. In fact, brief incubation of IL-1beta in normal cerebellar
      slices replicated EAE modifications through a rapid GLAST/EAAT1 downregulation,
      whereas incubation of an IL-1 receptor antagonist (IL-1ra) in EAE slices reduced
      spontaneous EPSC alterations. Finally, EAE mice treated with
      intracerebroventricular IL-1ra showed normal glutamatergic and GABAergic
      transmissions, along with GLAST/EAAT1 normalization, milder inflammation, and
      reduced motor deficits. These results highlight the crucial role played by the
      proinflammatory IL-1beta in triggering molecular and synaptic events involved in
      neurodegenerative processes that characterize neuroinflammatory diseases such as
      MS. 

PMID- 23864698
TI  - Feature extraction and integration underlying perceptual decision making during
      courtship behavior.
AB  - Traditionally, perceptual decision making is studied in trained animals and
      carefully controlled tasks. Here, we sought to elucidate the stimulus features
      and their combination underlying a naturalistic behavior--female decision making
      during acoustic courtship in grasshoppers. Using behavioral data, we developed a
      model in which stimulus features were extracted by physiologically plausible
      models of sensory neurons from the time-varying stimulus. This sensory evidence
      was integrated over the stimulus duration and combined to predict the behavior.
      We show that decisions were determined by the interaction of an excitatory and a
      suppressive stimulus feature. The observed increase of behavioral response with
      stimulus intensity was the result of an increase of the excitatory feature's gain
      that was not controlled by an equivalent increase of the suppressive feature.
      Differences in how these two features were combined could explain interindividual
      variability. In addition, the mapping between the two stimulus features and
      different parameters of the song led us to re-evaluate the cues underlying
      acoustic communication. Our framework provided a rich and plausible explanation
      of behavior in terms of two stimulus cues that were extracted by models of
      sensory neurons and combined through excitatory-inhibitory interactions. We thus
      were able to link single neuron's feature selectivity and network computations
      with decision making in a natural task. This data-driven approach has the
      potential to advance our understanding of decision making in other systems and
      can inform the search for the neural correlates of behavior.

PMID- 23864697
TI  - Phosphorylation of threonine-19 of PSD-95 by GSK-3beta is required for PSD-95
      mobilization and long-term depression.
AB  - Activity of glycogen synthase kinase-3beta (GSK-3beta) is required for long-term
      depression (LTD) via molecular mechanisms that are incompletely understood. Here,
      we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD)
      that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK
      3beta. In cultured rat hippocampal neurons, phosphorylation of T19 increases
      rapidly with chemical LTD and is attenuated by pharmacologic or genetic
      suppression of GSK-3beta. In organotypic rat hippocampal slices, we find that a
      nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green
      fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus
      wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily
      dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs
      AMPA receptor internalization and the induction of LTD. These data indicate that
      phosphorylation on T19 by GSK-3beta destabilizes PSD-95 within the PSD and is a
      critical step for AMPA receptor mobilization and LTD. 

PMID- 23864699
TI  - Clinical assessment determines the diagnosis of inclusion body myositis
      independently of pathological features.
AB  - BACKGROUND AND OBJECTIVE: Historically, the diagnosis of sporadic inclusion body
      myositis (IBM) has required the demonstration of the presence of a number of
      histopathological findings on muscle biopsy--namely, rimmed vacuoles, an
      inflammatory infiltrate with invasion of non-necrotic muscle fibres (partial
      invasion) and amyloid or 15-18 nm tubulofilamentous inclusions (Griggs criteria).
      However, biopsies of many patients with clinically typical IBM do not show all of
      these histopathological findings, at least at presentation. We compared the
      clinical features at presentation and during the course of disease in 67 patients
      with histopathologically diagnosed IBM and clinically diagnosed IBM seen within a
      single UK specialist muscle centre. METHODS AND RESULTS: At presentation, using
      clinically focused diagnostic criteria (European Neuromuscular Centre (ENMC)
      2011), a diagnosis of IBM was made in 88% of patients whereas 76% fulfilled the
      1997 ENMC criteria and only 27% satisfied the histopathologically focused Griggs
      criteria. There were no differences in clinical features or outcomes between
      clinically and histopathologically diagnosed patients, but patients lacking the
      classical histopathological finding of rimmed vacuoles were younger, suggesting
      that rimmed vacuoles may be a later feature of the disease. CONCLUSIONS: These
      findings have important implications for diagnosis and future studies or trials
      in IBM as adherence to histopathologically focused diagnostic criteria will
      exclude large numbers of patients with IBM. Importantly, those excluded may be at
      an earlier stage of the disease and more amenable to treatment.

PMID- 23864700
TI  - Vitamin D status is associated with functional limitations and functional decline
      in older individuals.
AB  - CONTEXT: Vitamin D is known to influence muscle health. A reduction in muscle
      mass increases the risk of functional limitations among older individuals.
      OBJECTIVE: The aim of this study was to examine the relationship between vitamin
      D status and functional limitations. DESIGN, SETTING, AND PARTICIPANTS: Two
      independent cohorts of the Longitudinal Aging Study Amsterdam were used.
      Participants were aged 65 to 88 years (older cohort, n = 1237; baseline 1995) and
      55 to 65 years (younger cohort, n = 725; baseline 2002). MAIN OUTCOME MEASURES:
      Questions on the ability and degree of difficulty to perform 6 functions of daily
      life were asked. RESULTS: Of the participants, 56% in the older cohort and 30% in
      the younger cohort had >=1 limitation. Vitamin D deficiency (25-hydroxyvitamin D
      level of <20 ng/mL) compared with the value in the reference group (>30 ng/mL)
      was related to the presence of functional limitations at baseline (odds ratio
      [OR] = 1.7; 95% confidence interval [CI], 1.2-2.5 and OR = 2.2; 95% CI 1.3-3.7
      for the older and younger cohorts, respectively). In the older cohort, vitamin D
      deficiency was associated with an increase in limitations at 3 years (OR = 2.0;
      95% CI, 1.1-3.5), whereas vitamin D deficiency in the younger cohort was
      associated with an increase in limitations at 6 years (OR = 3.3; 95% CI, 1.1
      10.1). Analyses were adjusted for confounders. CONCLUSION: Vitamin D status is
      associated with functional limitations cross-sectionally and longitudinally in
      individuals aged 55 to 65 years and those 65 years and older. The possible
      association of vitamin D with functional limitations is present after a shorter
      follow-up time in the oldest age group compared with the younger age group.

PMID- 23864701
TI  - Association between serum perfluorinated chemicals and thyroid function in U.S.
      adults: the National Health and Nutrition Examination Survey 2007-2010.
AB  - CONTEXT: Perfluorinated chemicals (PFCs) have been widely used in a variety of
      products worldwide for years. The relationship between serum PFCs and thyroid
      function has never been addressed in a nationally representative survey.
      OBJECTIVES: The study examined the association between serum PFCs and thyroid
      function in the general U.S. population. DESIGN AND PARTICIPANTS: We selected
      1181 subjects (aged >20 years) from a National Health and Nutrition Examination
      Survey (NHANES) in 2007 through 2008 and 2009 through 2010 to determine the
      relationship between serum PFCs and thyroid function. Data were adjusted for
      confounding variables. RESULTS: The geometric means and 95% confidence interval
      (CI) concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate,
      perfluorononanoic acid, and perfluorohexane sulfonate (PFHxS) were 4.15 (4.02
      4.29), 14.2 (13.59-14.86), 1.54 (1.48-1.59), and 2.00 (1.89-2.11) ng/mL,
      respectively. After weighting for sampling strategy, we determined a 1-U increase
      in natural log-serum PFOA increased serum total T3 concentration by 6.628 ng/dL
      (95% CI = 0.545-12.712, P = .035) in women. A 1-U increase in natural log-PFHxS
      was associated with an increase of total T4 by 0.26 MUg/mL (95% CI = 0.108-0.413,
      P = .002) and total T3 by 4.074 ng/dL (95% CI = 2.232-5.916, P < .001) in women
      and a decrease of natural log-free T4 by 0.016 (ng/dL) (95% CI = -0.029 to 0.003,
      P = .019) in men. CONCLUSION: Higher serum concentrations of PFOA and PFHxS are
      associated with total T3, total T4, and free T4 in the U.S. general population.
      More studies are warranted to clarify the causal relationship between PFCs and
      thyroid function.

PMID- 23864703
TI  - Association of circulating sclerostin with bone mineral mass, microstructure, and
      turnover biochemical markers in healthy elderly men and women.
AB  - CONTEXT: Sclerostin inhibits bone formation and is involved in the bone response
      to mechanical loading, but the role and significance of circulating sclerostin
      are poorly understood. OBJECTIVE: We assessed the association between serum
      sclerostin and calcitropic hormones, bone turnover marker levels, bone mineral
      content/density, and microstructure using 3 different immunoassays. DESIGN,
      SETTING, AND PARTICIPANTS: In a cross-sectional study, serum sclerostin was
      measured in a cohort of 187 healthy subjects (98 women; 89 men) aged 65 +/- 1 (+/
      SD) years. RESULTS: Overall, mean sclerostin (95% confidence interval) was 37.3
      (18.0-69.2) ng/L, 1165.8 (464.0-2296.4) ng/L, and 513.5 (250.7-950.9) ng/L with
      assays I, II, and III, respectively. Serum sclerostin was higher in men with
      assays II and III. In all 3 assays, sclerostin and PTH were inversely correlated,
      only after adjustment for whole-body bone mineral content (WB-BMC). After
      adjustment for sex and WB-BMC, the bone turnover markers amino-terminal
      propeptide of type I procollagen and carboxyterminal cross-linked telopeptide of
      type I collagen negatively correlated only with assay II. In all 3 assays,
      sclerostin positively correlated to WB-BMC, the distal radius and the distal
      tibia cortical area, cancellous bone volume and trabecular number, and lumbar
      spine and proximal femur areal bone mineral density after adjustment for sex.
      CONCLUSION: Sclerostin levels are markedly different according to the immunoassay
      used. Detection of an association with calcitropic hormones or turnover markers
      relies on the epitope recognized by the immunoassay and adjustment for bone mass.

PMID- 23864702
TI  - Decreased transcriptional activity of calcium-sensing receptor gene promoter 1 is
      associated with calcium nephrolithiasis.
AB  - BACKGROUND: CaSR gene is a candidate for calcium nephrolithiasis. Single
      nucleotide polymorphisms (SNPs) encompassing its regulatory region were
      associated with calcium nephrolithiasis. AIMS: We tested SNPs in the CaSR gene
      regulatory region associated with calcium nephrolithiasis and their effects in
      kidney. SUBJECTS AND METHODS: One hundred sixty-seven idiopathic calcium stone
      formers and 214 healthy controls were genotyped for four CaSR gene SNPs
      identified by bioinformatics analysis as modifying transcription factor binding
      sites. Strontium excretion after an oral load was tested in 55 stone formers.
      Transcriptional activity induced by variant alleles at CaSR gene promoters was
      compared by luciferase reporter gene assay in HEK-293 and HKC-8 cells. CaSR and
      claudin-14 mRNA levels were measured by real-time PCR in 107 normal kidney
      medulla samples and compared in patients with different CaSR genotype. RESULTS:
      Only rs6776158 (A>G), located in the promoter 1, was associated with
      nephrolithiasis. Its minor G allele was more frequent in stone formers than
      controls (37.8% vs 26.4%, P = .001). A reduced strontium excretion was observed
      in GG homozygous stone formers. Luciferase fluorescent activity was lower in
      cells transfected with the promoter 1 including G allele at rs6776158 than cells
      transfected with the A allele. CaSR mRNA levels were lower in kidney medulla
      samples from homozygous carriers for the G allele at rs6776158 than carriers for
      the A allele. Claudin-14 mRNA levels were also lower in GG homozygous subjects.
      CONCLUSIONS: Minor allele at rs6776158 may predispose to calcium stones by
      decreasing transcriptional activity of the CaSR gene promoter 1 and CaSR
      expression in kidney tubules.

PMID- 23864704
TI  - Modulation of inositol polyphosphate levels regulates neuronal differentiation.
AB  - The binding of neurotrophins to tropomyosin receptor kinase receptors initiates
      several signaling pathways, including the activation of phospholipase C-gamma,
      which promotes the release of diacylglycerol and inositol 1,4,5-trisphosphate
      (IP(3)). In addition to recycling back to inositol, IP(3) serves as a precursor
      for the synthesis of higher phosphorylated inositols, such as inositol 1,3,4,5,6
      pentakisphosphate (IP(5)) and inositol hexakisphosphate (IP(6)). Previous studies
      on the effect of neurotrophins on inositol signaling were limited to the analysis
      of IP(3) and its dephosphorylation products. Here we demonstrate that nerve
      growth factor (NGF) regulates the levels of IP(5) and IP(6) during PC12
      differentiation. Furthermore, both NGF and brain-derived neurotrophic factor
      alter IP(5) and IP(6) intracellular ratio in differentiated PC12 cells and
      primary neurons. Neurotrophins specifically regulate the expression of IP(5)-2
      kinase (IP(5)-2K), which phosphorylates IP(5) into IP(6). IP(5)-2K is rapidly
      induced after NGF treatment, but its transcriptional levels sharply decrease in
      fully differentiated PC12 cells. Reduction of IP(5)-2K protein levels by small
      interfering RNA has an effect on the early stages of PC12 cell differentiation,
      whereas fully differentiated cells are not affected. Conversely, perturbation of
      IP(5)-2K levels by overexpression suggests that both differentiated PC12 cells
      and sympathetic neurons require low levels of the enzyme for survival. Therefore
      maintaining appropriate intracellular levels of inositol polyphosphates is
      necessary for neuronal survival and differentiation.

PMID- 23864705
TI  - Myosin-1c regulates the dynamic stability of E-cadherin-based cell-cell contacts
      in polarized Madin-Darby canine kidney cells.
AB  - Cooperation between cadherins and the actin cytoskeleton controls the formation
      and maintenance of cell-cell adhesions in epithelia. We find that the molecular
      motor protein myosin-1c (Myo1c) regulates the dynamic stability of E-cadherin
      based cell-cell contacts. In Myo1c-depleted Madin-Darby canine kidney cells, E
      cadherin localization was dis-organized and lateral membranes appeared less
      vertical with convoluted edges versus control cells. In polarized monolayers,
      Myo1c-knockdown (KD) cells were more sensitive to reduced calcium concentration.
      Myo1c separated in the same plasma membrane fractions as E-cadherin, and Myo1c KD
      caused a significant reduction in the amount of E-cadherin recovered in one peak
      fraction. Expression of green fluorescent protein (GFP)-Myo1c mutants revealed
      that the phosphatidylinositol-4,5-bisphosphate-binding site is necessary for its
      localization to cell-cell adhesions, and fluorescence recovery after
      photobleaching assays with GFP-Myo1c mutants revealed that motor function was
      important for Myo1c dynamics at these sites. At 18 degrees C, which inhibits
      vesicle recycling, Myo1c-KD cells accumulated more E-cadherin-positive vesicles
      in their cytoplasm, suggesting that Myo1c affects E-cadherin endocytosis. Studies
      with photoactivatable GFP-E-cadherin showed that Myo1c KD reduced the stability
      of E-cadherin at cell-cell adhesions. We conclude that Myo1c stabilizes E
      cadherin at adherens junctions in polarized epithelial cells and that the motor
      function and ability of Myo1c to bind membrane are critical. 

PMID- 23864706
TI  - A complex of Cox4 and mitochondrial Hsp70 plays an important role in the assembly
      of the cytochrome c oxidase.
AB  - The formation of the mature cytochrome c oxidase (complex IV) involves the
      association of nuclear- and mitochondria-encoded subunits. The assembly of
      nuclear-encoded subunits like cytochrome c oxidase subunit 4 (Cox4) into the
      mature complex is poorly understood. Cox4 is crucial for the stability of complex
      IV. To find specific biogenesis factors, we analyze interaction partners of Cox4
      by affinity purification and mass spectroscopy. Surprisingly, we identify a
      complex of Cox4, the mitochondrial Hsp70 (mtHsp70), and its nucleotide-exchange
      factor mitochondrial GrpE (Mge1). We generate a yeast mutant of mtHsp70
      specifically impaired in the formation of this novel mtHsp70-Mge1-Cox4 complex.
      Strikingly, the assembly of Cox4 is strongly decreased in these mutant
      mitochondria. Because Cox4 is a key factor for the biogenesis of complex IV, we
      conclude that the mtHsp70-Mge1-Cox4 complex plays an important role in the
      formation of cytochrome c oxidase. Cox4 arrests at this chaperone complex in the
      absence of mature complex IV. Thus the mtHsp70-Cox4 complex likely serves as a
      novel delivery system to channel Cox4 into the assembly line when needed. 

PMID- 23864707
TI  - Sit4p/PP6 regulates ER-to-Golgi traffic by controlling the dephosphorylation of
      COPII coat subunits.
AB  - Traffic from the endoplasmic reticulum (ER) to the Golgi complex is initiated
      when the activated form of the GTPase Sar1p recruits the Sec23p-Sec24p complex to
      ER membranes. The Sec23p-Sec24p complex, which forms the inner shell of the COPII
      coat, sorts cargo into ER-derived vesicles. The coat inner shell recruits the
      Sec13p-Sec31p complex, leading to coat polymerization and vesicle budding. Recent
      studies revealed that the Sec23p subunit sequentially interacts with three
      different binding partners to direct a COPII vesicle to the Golgi. One of these
      binding partners is the serine/threonine kinase Hrr25p. Hrr25p phosphorylates the
      COPII coat, driving the membrane-bound pool into the cytosol. The phosphorylated
      coat cannot rebind to the ER to initiate a new round of vesicle budding unless it
      is dephosphorylated. Here we screen all known protein phosphatases in yeast to
      identify one whose loss of function alters the cellular distribution of COPII
      coat subunits. This screen identifies the PP2A-like phosphatase Sit4p as a
      regulator of COPII coat dephosphorylation. Hyperphosphorylated coat subunits
      accumulate in the sit4Delta mutant in vivo. In vitro, Sit4p dephosphorylates
      COPII coat subunits. Consistent with a role in coat recycling, Sit4p and its
      mammalian orthologue, PP6, regulate traffic from the ER to the Golgi complex. 

PMID- 23864708
TI  - Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness
      and chemoresistance of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is almost always lethal. One of the
      underlying reasons for this lethality is believed to be the presence of cancer
      stem cells (CSC), which impart chemoresistance and promote recurrence, but the
      mechanisms responsible are unclear. Recently the poor prognosis of PDAC has been
      correlated with increased expression of urokinase plasminogen activator (uPA). In
      the present study we examine the role of uPA in the generation of PDAC CSC. We
      observe a subset of cells identifiable as a side population (SP) when sorted by
      flow cytometry of MIA PaCa-2 and PANC-1 pancreatic cancer cells that possess the
      properties of CSC. A large fraction of these SP cells are CD44 and CD24 positive,
      are gemcitabine resistant, possess sphere-forming ability, and exhibit increased
      tumorigenicity, known characteristics of cancer stemness. Increased
      tumorigenicity and gemcitabine resistance decrease after suppression of uPA. We
      observe that uPA interacts directly with transcription factors LIM homeobox-2
      (Lhx2), homeobox transcription factor A5 (HOXA5), and Hey to possibly promote
      cancer stemness. uPA regulates Lhx2 expression by suppressing expression of miR
      124 and p53 expression by repressing its promoter by inactivating HOXA5. These
      results demonstrate that regulation of gene transcription by uPA contributes to
      cancer stemness and clinical lethality. 

PMID- 23864709
TI  - Rho GTPase-independent regulation of mitotic progression by the RhoGEF Net1.
AB  - Neuroepithelial transforming gene 1 (Net1) is a RhoA-subfamily-specific guanine
      nucleotide exchange factor that is overexpressed in multiple human cancers and is
      required for proliferation. Molecular mechanisms underlying its role in cell
      proliferation are unknown. Here we show that overexpression or knockdown of Net1
      causes mitotic defects. Net1 is required for chromosome congression during
      metaphase and generation of stable kinetochore microtubule attachments.
      Accordingly, inhibition of Net1 expression results in spindle assembly checkpoint
      activation. The ability of Net1 to control mitosis is independent of RhoA or RhoB
      activation, as knockdown of either GTPase does not phenocopy effects of Net1
      knockdown on nuclear morphology, and effects of Net1 knockdown are effectively
      rescued by expression of catalytically inactive Net1. We also observe that Net1
      expression is required for centrosomal activation of p21-activated kinase and its
      downstream kinase Aurora A, which are critical regulators of centrosome
      maturation and spindle assembly. These results identify Net1 as a novel regulator
      of mitosis and indicate that altered expression of Net1, as occurs in human
      cancers, may adversely affect genomic stability. 

PMID- 23864710
TI  - Plasma membrane domains enriched in cortical endoplasmic reticulum function as
      membrane protein trafficking hubs.
AB  - In mammalian cells, the cortical endoplasmic reticulum (cER) is a network of
      tubules and cisterns that lie in close apposition to the plasma membrane (PM). We
      provide evidence that PM domains enriched in underlying cER function as
      trafficking hubs for insertion and removal of PM proteins in HEK 293 cells. By
      simultaneously visualizing cER and various transmembrane protein cargoes with
      total internal reflectance fluorescence microscopy, we demonstrate that the
      majority of exocytotic delivery events for a recycled membrane protein or for a
      membrane protein being delivered to the PM for the first time occur at regions
      enriched in cER. Likewise, we observed recurring clathrin clusters and functional
      endocytosis of PM proteins preferentially at the cER-enriched regions. Thus the
      cER network serves to organize the molecular machinery for both insertion and
      removal of cell surface proteins, highlighting a novel role for these unique
      cellular microdomains in membrane trafficking. 

PMID- 23864711
TI  - Superoxide radicals have a protective role during H2O2 stress.
AB  - Reactive oxygen species (ROS) consist of potentially toxic, partly reduced oxygen
      species and free radicals. After H(2)O(2) treatment, yeast cells significantly
      increase superoxide radical production. Respiratory chain complex III and
      possibly cytochrome b function are essential for this increase. Disruption of
      complex III renders cells sensitive to H(2)O(2) but not to the superoxide radical
      generator menadione. Of interest, the same H(2)O(2)-sensitive mutant strains have
      the lowest superoxide radical levels, and strains with the highest resistance to
      H(2)O(2) have the highest levels of superoxide radicals. Consistent with this
      correlation, overexpression of superoxide dismutase increases sensitivity to
      H(2)O(2), and this phenotype is partially rescued by addition of small
      concentrations of menadione. Small increases in levels of mitochondrially
      produced superoxide radicals have a protective effect during H(2)O(2)-induced
      stress, and in response to H(2)O(2), the wild-type strain increases superoxide
      radical production to activate this defense mechanism. This provides a direct
      link between complex III as the main source of ROS and its role in defense
      against ROS. High levels of the superoxide radical are still toxic. These
      opposing, concentration-dependent roles of the superoxide radical comprise a form
      of hormesis and show one ROS having a hormetic effect on the toxicity of another.

PMID- 23864712
TI  - UDP-glucose:glycoprotein glucosyltransferase (UGGT1) promotes substrate
      solubility in the endoplasmic reticulum.
AB  - Protein folding in the endoplasmic reticulum (ER) is error prone, and ER quality
      control (ERQC) processes ensure that only correctly folded proteins are exported
      from the ER. Glycoproteins can be retained in the ER by ERQC, and this retention
      contributes to multiple human diseases, termed ER storage diseases. UDP
      glucose:glycoprotein glucosyltransferase (UGGT1) acts as a central component of
      glycoprotein ERQC, monoglucosylating deglucosylated N-glycans of incompletely
      folded glycoproteins and promoting subsequent reassociation with the lectin-like
      chaperones calreticulin and calnexin. The extent to which UGGT1 influences
      glycoprotein folding, however, has only been investigated for a few selected
      substrates. Using mouse embryonic fibroblasts lacking UGGT1 or those with UGGT1
      complementation, we investigated the effect of monoglucosylation on the
      soluble/insoluble distribution of two misfolded alpha1-antitrypsin (AAT) variants
      responsible for AAT deficiency disease: null Hong Kong (NHK) and Z allele.
      Whereas substrate solubility increases directly with the number of N-linked
      glycosylation sites, our results indicate that additional solubility is conferred
      by UGGT1 enzymatic activity. Monoglucosylation-dependent solubility decreases
      both BiP association with NHK and unfolded protein response activation, and the
      solubility increase is blocked in cells deficient for calreticulin. These results
      suggest that UGGT1-dependent monoglucosylation of N-linked glycoproteins promotes
      substrate solubility in the ER. 

PMID- 23864713
TI  - WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar
      transport in cilia.
AB  - Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We
      identify a Chlamydomonas flagellar protein (flagellar-associated protein 163
      [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC)
      of the dynein that powers this movement. Biochemical analysis revealed that
      FAP163 is present in the flagellar matrix and is actively trafficked by IFT.
      Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain,
      indicating that it is an integral component of the retrograde IFT dynein. To
      assess the functional role of FAP163, we generated an RNA interference knockdown
      of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a
      severe ciliary assembly defect that dramatically compromised whole-organism
      motility. Most cilia were present as short stubs that had accumulated large
      quantities of IFT particle-like material between the doublet microtubules and the
      membrane. The few remaining approximately full-length cilia had a chaotic beat
      with a frequency reduced from 24 to ~10 Hz. Thus WD60/FAP163 is a dynein IC that
      is absolutely required for retrograde IFT and ciliary assembly. 

PMID- 23864714
TI  - Abnormal centrosomal structure and duplication in Cep135-deficient vertebrate
      cells.
AB  - Centrosomes are key microtubule-organizing centers that contain a pair of
      centrioles, conserved cylindrical, microtubule-based structures. Centrosome
      duplication occurs once per cell cycle and relies on templated centriole
      assembly. In many animal cells this process starts with the formation of a
      radially symmetrical cartwheel structure. The centrosomal protein Cep135
      localizes to this cartwheel, but its role in vertebrates is not well understood.
      Here we examine the involvement of Cep135 in centriole function by disrupting the
      Cep135 gene in the DT40 chicken B-cell line. DT40 cells that lack Cep135 are
      viable and show no major defects in centrosome composition or function, although
      we note a small decrease in centriole numbers and a concomitant increase in the
      frequency of monopolar spindles. Furthermore, electron microscopy reveals an
      atypical structure in the lumen of Cep135-deficient centrioles. Centrosome
      amplification after hydroxyurea treatment increases significantly in Cep135
      deficient cells, suggesting an inhibitory role for the protein in centrosome
      reduplication during S-phase delay. We propose that Cep135 is required for the
      structural integrity of centrioles in proliferating vertebrate cells, a role that
      also limits centrosome amplification in S-phase-arrested cells. 

PMID- 23864715
TI  - Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis.
AB  - Calcium-dependent cysteine proteases of the calpain family are modulatory
      proteases that cleave their substrates in a limited manner. Among their
      substrates, calpains target vertebrate and invertebrate IkappaB proteins. Because
      proteolysis by calpains potentially generates novel protein functions, it is
      important to understand how this affects NFkappaB activity. We investigate the
      action of Calpain A (CalpA) on the Drosophila melanogaster IkappaB homologue
      Cactus in vivo. CalpA alters the absolute amounts of Cactus protein. Our data
      indicate, however, that CalpA uses additional mechanisms to regulate NFkappaB
      function. We provide evidence that CalpA interacts physically with Cactus,
      recognizing a Cactus pool that is not bound to Dorsal, a fly NFkappaB/Rel
      homologue. We show that proteolytic cleavage by CalpA generates Cactus fragments
      lacking an N-terminal region required for Toll responsiveness. These fragments
      are generated in vivo and display properties distinct from those of full-length
      Cactus. We propose that CalpA targets free Cactus, which is incorporated into and
      modulates Toll-responsive complexes in the embryo and immune system. 

PMID- 23864716
TI  - Rap-afadin axis in control of Rho signaling and endothelial barrier recovery.
AB  - Activation of the Rho GTPase pathway determines endothelial cell (EC)
      hyperpermeability after injurious stimuli. To date, feedback mechanisms of Rho
      down-regulation critical for barrier restoration remain poorly understood. We
      tested a hypothesis that Rho down-regulation and barrier recovery of agonist
      stimulated ECs is mediated by the Ras family GTPase Rap1. Thrombin-induced EC
      permeability driven by rapid activation of the Rho GTPase pathway was followed by
      Src kinase-dependent phosphorylation of the Rap1-specific guanine nucleotide
      exchange factor (GEF) C3G, activation of Rap1, and initiation of EC barrier
      recovery. Knockdown experiments showed that Rap1 activation was essential for
      down-regulation of Rho signaling and actin stress fiber dissolution. Rap1
      activation also enhanced interaction between adherens junction (AJ) proteins VE
      cadherin and p120-catenin and stimulated AJ reannealing mediated by the Rap1
      effector afadin. This mechanism also included Rap1-dependent membrane
      translocation of the Rac1-specific GEF Tiam1 and activation of Rac1-dependent
      peripheral cytoskeletal dynamics, leading to resealing of intercellular gaps.
      These data demonstrate that activation of the Rap1-afadin axis is a physiological
      mechanism driving restoration of barrier integrity in agonist-stimulated EC
      monolayers via negative-feedback regulation of Rho signaling, stimulation of
      actin peripheral dynamics, and reestablishment of cell-cell adhesive complexes. 

PMID- 23864718
TI  - Nigrostriatal dopamine terminal imaging with dopamine transporter SPECT: an
      update.
AB  - This article gives an update on nigrostriatal dopamine terminal imaging, with
      emphasis on SPECT performed with the presynaptic dopamine transporter (DAT)
      ligand (123)I-FP-CIT. The paper covers the rational use of this technique in the
      diagnostic work-up of patients with known or suspected parkinsonian syndromes. In
      detail, it addresses the impact of the method for the proof or exclusion of
      neurodegenerative parkinsonism, for its early and preclinical diagnosis, and for
      the evaluation of disease progression. The importance of normal DAT binding for
      differentiating symptomatic parkinsonism and relevant tremor syndromes from
      neurodegeneration is highlighted. Particularly emphasized is the role of DAT
      SPECT for diagnosing Lewy body dementia and its separation from Alzheimer
      dementia. Finally, some remarks deal with the economic aspects of the use of
      these imaging techniques in the clinical setting. 

PMID- 23864717
TI  - The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi
      network and subsequent acrosome formation in spermiogenesis.
AB  - The trans-Golgi network (TGN) functions as a hub organelle in the exocytosis of
      clathrin-coated membrane vesicles, and SMAP2 is an Arf GTPase-activating protein
      that binds to both clathrin and the clathrin assembly protein (CALM). In the
      present study, SMAP2 is detected on the TGN in the pachytene spermatocyte to the
      round spermatid stages of spermatogenesis. Gene targeting reveals that SMAP2
      deficient male mice are healthy and survive to adulthood but are infertile and
      exhibit globozoospermia. In SMAP2-deficient spermatids, the diameter of
      proacrosomal vesicles budding from TGN increases, TGN structures are distorted,
      acrosome formation is severely impaired, and reorganization of the nucleus does
      not proceed properly. CALM functions to regulate vesicle sizes, and this study
      shows that CALM is not recruited to the TGN in the absence of SMAP2. Furthermore,
      syntaxin2, a component of the soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) complex, is not properly concentrated at the
      site of acrosome formation. Thus this study reveals a link between SMAP2 and
      CALM/syntaxin2 in clathrin-coated vesicle formation from the TGN and subsequent
      acrosome formation. SMAP2-deficient mice provide a model for globozoospermia in
      humans. 

PMID- 23864719
TI  - 18F-FDG PET early response evaluation of locally advanced non-small cell lung
      cancer treated with concomitant chemoradiotherapy.
AB  - The potential of (18)F-FDG PET changes was evaluated for prediction of response
      to concomitant chemoradiotherapy in patients with locally advanced non-small cell
      lung cancer (NSCLC). METHODS: For 28 patients, (18)F-FDG PET was performed before
      treatment, at the end of the second week of treatment, and at 2 wk and 3 mo after
      the completion of treatment. Standardized uptake value (SUV), maximum SUV,
      metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained.
      Early metabolic changes were defined as fractional change (DeltaTLG) when (18)F
      FDG PET at the end of the second week was compared with pretreatment (18)F-FDG
      PET. In-treatment metabolic changes, as measured by serial (18)F-FDG PET, were
      correlated with standard criteria of response evaluation of solid tumors by means
      of CT imaging (Response Evaluation Criteria In Solid Tumors 1.1). Parameters were
      analyzed for stratification in progression-free survival (PFS). RESULTS: When
      compared with early metabolic nonresponders, a DeltaTLG decrease of 38% or more
      was associated with a significantly longer PFS (1-y PFS 80% vs. 36%, P = 0.02).
      Pretreatment TLG was found to be a prognostic factor for PFS. CONCLUSION: The
      degree of change in TLG was predictive for response to concomitant
      chemoradiotherapy as early as the end of the second week into treatment for
      patients with locally advanced NSCLC. Pretreatment TLG was prognostic for PFS.

PMID- 23864720
TI  - Longitudinal progression of cognitive decline correlates with changes in the
      spatial pattern of brain 18F-FDG PET.
AB  - Evaluating the symptomatic progression of mild cognitive impairment (MCI) caused
      by Alzheimer disease (AD) is practically accomplished by tracking performance on
      cognitive tasks, such as the Alzheimer Disease Assessment Scale's cognitive
      subscale (ADAS_cog), the Mini-Mental Status Examination (MMSE), and the
      Functional Activities Questionnaire (FAQ). The longitudinal relationships between
      cognitive decline and metabolic function as assessed using (18)F-FDG PET are
      needed to address both the cognitive and the biologic progression of disease
      state in individual subjects. We conducted an exploratory investigation to
      evaluate longitudinal changes in brain glucose metabolism of individual subjects
      and their relationship to the subject's changes of cognitive status. METHODS: We
      describe a method to determine correlations in (18)F-FDG spatial distribution
      over time. This parameter is termed the regional (18)F-FDG time correlation
      coefficient (rFTC). By using linear mixed-effects models, we determined the
      difference in the rFTC decline rate between controls and subjects at high risk of
      developing AD, such as individuals with MCI or the presence of apolipoprotein E
      (APOE)-epsilon4 allele. The association between each subject's rFTC and
      performance on cognitive tests (ADAS_cog, MMSE, and FAQ) was determined with 2
      different correlation methods. All subject data were downloaded from the
      Alzheimer Disease Neuroimaging Initiative. RESULTS: The rFTC values of controls
      remained fairly constant over time (-0.003 annual change; 95% confidence
      interval, -0.010-0.004). In MCI patients, the rFTC declined faster than in
      controls by an additional annual change of -0.02 (95% confidence interval, -0.030
      to -0.010). In MCI patients, the decline in rFTC was associated with cognitive
      decline (ADAS_cog, P = 0.011; FAQ, P = 0.0016; MMSE, P = 0.004). After a linear
      effect of time was accounted for, visit-to-visit changes in rFTC correlated with
      visit-to-visit changes in all 3 cognitive tests. CONCLUSION: Longitudinal changes
      in rFTC detect subtle metabolic changes in individuals associated with variations
      in their cognition. This analytic tool may be useful for a patient-based
      monitoring of cognitive decline.

PMID- 23864721
TI  - Extensive trans-specific polymorphism at the mating type locus of the root decay
      fungus Heterobasidion.
AB  - Incompatibility systems in which individuals bearing identical alleles reject
      each other favor the maintenance of a diversity of alleles. Mushroom mating type
      loci (MAT) encode for dozens or hundreds of incompatibility alleles whose loss
      from the population is greatly restricted through negative frequency selection,
      leading to a system of alleles with highly divergent sequences. Here, we use DNA
      sequences of homeodomain (HD) encoding genes at the MAT locus of five closely
      related species of the root rot basidiomycete Heterobasidion annosum sensu lato
      to show that the extended coalescence time of MAT alleles greatly predates
      speciation in the group, contrasting loci outside of MAT that show allele
      divergences largely consistent with the species phylogeny with those of MAT,
      which show rampant trans-species polymorphism. We observe a roughly 6-fold
      greater genealogical depth and polymorphism of MAT compared with non-MAT that
      argues for the maintenance of balanced polymorphism for a minimum duration of 24
      My based on a molecular-clock calibrated species phylogeny. As with other
      basidiomycete HD genes, balancing selection appears to be concentrated at the
      specificity-determining region in the N-terminus of the protein based on
      identification of codons under selection and the absence of recombination within
      the region. However, the elevated polymorphism extends into the nonspecificity
      determining regions as well as a neighboring non-MAT gene, the mitochondrial
      intermediate peptidase (MIP). In doing so, increased divergence should decrease
      recombination among alleles and as a by-product create incompatibilities in the
      functional domains not involved in allele recognition but in regulating sexual
      development. 

PMID- 23864722
TI  - Old suspect--new evidence: the role of PKCbeta in diabetes mellitus-accelerated
      atherosclerosis.

PMID- 23864723
TI  - MicroRNAs in stem cell function and regenerative therapy of the heart.
AB  - MicroRNAs are small noncoding RNAs that posttranscriptionally control gene
      expression by targeting mRNAs. Distinct microRNAs regulate stem and progenitor
      cell functions, thereby modulating cell survival and homing or controlling
      differentiation and maturation. Experimental studies additionally show that
      microRNAs regulate endogenous repair and might potentially be useful to enhance
      the regeneration of the heart. This review summarizes the current studies that
      address the use of microRNAs to either improve cellular therapies or that might
      be targeted for enhancing endogenous tissue repair and regeneration after
      myocardial infarction. 

PMID- 23864724
TI  - Superactivated platelets: thrombus regulators, thrombin generators, and potential
      clinical targets.
AB  - Platelets contribute to hemostasis by forming the platelet plug and then
      contributing to coagulation by providing a catalytic surface where thrombin
      generation occurs efficiently. This catalytic activity, known as the platelet
      procoagulant response, is being recognized as a nuanced response. This review
      examines platelets' response to strong stimuli, which results in the formation of
      a platelet subpopulation (superactivated platelets) with several unique
      properties, including enhanced procoagulant activity. These platelets contribute
      uniquely to thrombus architecture and seem to have thrombus regulatory activity.
      Superactivated platelets' role in diseases of thrombosis and hemostasis, as
      either potentiating or mitigating factors, is not currently known, but may be an
      important pharmacological target. 

PMID- 23864729
TI  - AIM2, an IFN-inducible cytosolic DNA sensor, in the development of benign
      prostate hyperplasia and prostate cancer.
AB  - Close links have been noted between chronic inflammation of the prostate and the
      development of human prostatic diseases such as benign prostate hyperplasia (BPH)
      and prostate cancer. However, the molecular mechanisms that contribute to
      prostatic inflammation remain largely unexplored. Recent studies have indicated
      that the IFN-inducible AIM2 protein is a cytosolic DNA sensor in macrophages and
      keratinocytes. Upon sensing DNA, AIM2 recruits the adaptor ASC and pro-CASP1 to
      assemble the AIM2 inflammasome. Activation of the AIM2 inflammasome cleaves pro
      interleukin (IL)-1beta and pro-IL-18 and promotes the secretion of IL-1beta and
      IL-18 proinflammatory cytokines. Given that human prostatic infections are
      associated with chronic inflammation, the development of BPH is associated with
      an accumulation of senescent cells with a proinflammatory phenotype, and the
      development of prostate cancer is associated with the loss of IFN signaling, the
      role of AIM2 in mediating the formation of prostatic diseases was investigated.
      It was determined that IFNs (alpha, beta, or gamma) induced AIM2 expression in
      human prostate epithelial cells and cytosolic DNA activated the AIM2
      inflammasome. Steady-state levels of the AIM2 mRNA were higher in BPH than in
      normal prostate tissue. However, the levels of AIM2 mRNA were significantly lower
      in clinical tumor specimens. Accordingly, constitutive levels of AIM2 mRNA and
      protein were lower in a subset of prostate cancer cells as compared with BPH
      cells. Further, the cytosolic DNA activated the AIM2 inflammasome in the androgen
      receptor-negative PC3 prostate cancer cell line, suggesting that AIM2-mediated
      events are independent of androgen receptor status. IMPLICATIONS: The AIM2
      inflammasome has a fundamental role in the generation of human prostatic
      diseases.

PMID- 23864730
TI  - SW#-GPU-enabled exact alignments on genome scale.
AB  - SUMMARY: We propose SW#, a new CUDA graphical processor unit-enabled and memory
      efficient implementation of dynamic programming algorithm, for local alignment.
      It can be used as either a stand-alone application or a library. Although there
      are other graphical processor unit implementations of the Smith-Waterman
      algorithm, SW# is the only one publicly available that can produce sequence
      alignments on genome-wide scale. For long sequences, it is at least a few hundred
      times faster than a CPU version of the same algorithm. AVAILABILITY: Source code
      and installation instructions freely available for download at
      http://complex.zesoi.fer.hr/SW.html.

PMID- 23864731
TI  - deltaGseg: macrostate estimation via molecular dynamics simulations and
      multiscale time series analysis.
AB  - SUMMARY: Binding free energy calculations obtained through molecular dynamics
      simulations reflect intermolecular interaction states through a series of
      independent snapshots. Typically, the free energies of multiple simulated series
      (each with slightly different starting conditions) need to be estimated. Previous
      approaches carry out this task by moving averages at certain decorrelation times,
      assuming that the system comes from a single conformation description of binding
      events. Here, we discuss a more general approach that uses statistical modeling,
      wavelets denoising and hierarchical clustering to estimate the significance of
      multiple statistically distinct subpopulations, reflecting potential macrostates
      of the system. We present the deltaGseg R package that performs macrostate
      estimation from multiple replicated series and allows molecular
      biologists/chemists to gain physical insight into the molecular details that are
      not easily accessible by experimental techniques. AVAILABILITY: deltaGseg is a
      Bioconductor R package available at
      http://bioconductor.org/packages/release/bioc/html/deltaGseg.html.

PMID- 23864732
TI  - Twist-DNA: computing base-pair and bubble opening probabilities in genomic
      superhelical DNA.
AB  - SUMMARY: Local opening of the DNA double helix is required in many fundamental
      biological processes and is, in part, controlled by the degree of superhelicity
      imposed in vivo by the protein machinery. In particular, positions of
      superhelically destabilized regions correlate with regulatory sites along the
      genome. Based on a self-consistent linearization of a thermodynamic model of
      superhelical DNA introduced by Benham, we have developed a program that predicts
      the locations of these regions by efficiently computing base-pair and bubble
      opening probabilities in genomic DNA. The program allows visualization of results
      in standard genome browsers to compare DNA opening properties with other
      available datasets. AVAILABILITY AND IMPLEMENTATION: Source codes freely
      available for download at http://www.cbp.ens
      lyon.fr/doku.php?id=developpement:productions:logiciels:twistdna, implemented in
      Fortran90 and supported on any Unix-based operating system (Linux, Mac OS X).

PMID- 23864733
TI  - The status of fatherhood and fathering in South Africa.
AB  - This paper begins with estimates of fatherhood in South Africa, in the absence of
      formal measures of paternity. It highlights several salient features of
      fatherhood in the country, particularly low rates of marriages and father absence
      from households, and it traces their roots in colonialism and Apartheid, the
      political system in South Africa under which Black people were systematically
      oppressed. We point out that some forms of father absence illustrate the
      commitment of men to supporting their families by their willingness to seek
      migrant work far from their homes. Examples are given of government policies to
      support fathers and some of the major civil society efforts are described. The
      paper closes with important themes about fatherhood in work with young children.

PMID- 23864734
TI  - Children's Learning in the Diverse Socio-Cultural Context of South Africa.
AB  - Children develop in several interlocking systems-in the context of their family,
      and within the interaction of settings such as home, school, and church (Russell,
      2011). In South Africa, children's diverse backgrounds within families,
      neighborhoods and socio-cultural environments provide them with varied
      experiences and opportunities to learn. Whether growing up in urban or rural
      communities, belonging to a specific race and ethnic group, or being poor or
      rich, all imply exposure to cultures, lifestyles, amenities, and living
      conditions that differ in marked ways (Makoe, 2006). With 79% of the total
      population being Blacks, the racial and ethnic heterogeneity translates into a
      complex mix of languages: English, Afrikaans, nine indigenous languages and five
      Indian languages are spoken (Reagan, 2001).

PMID- 23864735
TI  - Synthesis of OMS Materials and Investigation of Their Acceptor-Donor
      Characteristics.
AB  - Three ordered mesoporous siliceous (OMS) materials known as MCM41s-unmodified MCM
      41C16 ("C16"), and two MCM41s with different surface functionalities: MCM-41C16
      SH ("C16-SH") and MCM-41C16-NH2 ("C16-NH2")-were synthesized and studied by
      inverse gas chromatography in order to determine their acceptor-donor properties.
      The specific retention volumes of nonpolar and polar probes that were
      chromatographed on these ordered mesoporous silica adsorbents were evaluated
      under infinite dilution conditions. Two methods were employed to calculate the
      standard free energy of adsorption, DeltaGads, of each chromatographed probe on
      the basis its specific retention volume. These DeltaGads values were then
      employed to estimate the van der Waals contribution and the specific contribution
      of the free surface energy for each MCM41. DN values (donor numbers, based on the
      Gutmann scale) and AN* values (acceptor numbers, based on the Riddle-Fowkes
      scale) were employed to determine the values of parameters that characterize the
      ability of the MCM41s to act as electron acceptors (parameter: KA) and donors
      (parameter: KD). Considering the different compositions of the probes, each of
      which has different acceptor-donor properties, a new chromatographic test to
      supplement the Grob test is suggested.

PMID- 23864736
TI  - Optimization and Simultaneous Determination of Alkyl Phenol Ethoxylates and
      Brominated Flame Retardants in Water after SPE and Heptafluorobutyric Anhydride
      Derivatization followed by GC/MS.
AB  - A gas chromatography-mass spectrometry (GC-MS) method was investigated for the
      simultaneous analysis of two types of endocrine disrupting compounds (EDCs),
      i.e., alkylphenol ethoxylates and brominated flame retardants (BFRs), by
      extraction and derivatization followed by GC-MS. Different solid phase extraction
      (SPE) cartridges (Cleanert PestiCarb, C18, Cleanert-SAX and Florosil), solvents
      (toluene, tetrahydrofuran, acetone, acetonitrile and ethyl acetate) and bases
      (NaHCO3, triethylamine and pyridine) were tested and the best chromatographic
      analysis was achieved by extraction with Strata-X (33 MUm, Reverse Phase)
      cartridge and derivatization with heptafluorobutyric anhydride at 55  degrees C
      under Na2CO3 base in hexane. It was observed that APE together with lower
      substituted PBBs (PBB1, PBB10, PBB18 and PBB49), HBCD and TBBPA can be determined
      simultaneously under the same GC conditions. This simple and reliable analytical
      method was applied to determining trace amounts of these compounds from
      wastewater treatment plant samples. The recoveries of the target compounds from
      simulated water were above 60 %. The limit of detection ranged from 0.01 to 0.15
      MUg L-1 and the limit of quantification ranged from 0.05 to 0.66 MUg L-1. There
      were no appreciable differences between filtered and unfiltered wastewater
      samples from Leeuwkil treatment plant although concentration of target analytes
      in filtered influent was slightly lower than the concentration of target analytes
      in unfiltered influent water. The concentrations of the target compounds from the
      wastewater treatment were determined from LOQ upwards.

PMID- 23864737
TI  - Loop-mediated isothermal amplification targeting 18S ribosomal DNA for rapid
      detection of Acanthamoeba.
AB  - Amoebic keratitis (AK) caused by Acanthamoeba is one of the most serious corneal
      infections. AK is frequently misdiagnosed initially as viral, bacterial, or
      fungal keratitis, thus ensuring treatment delays. Accordingly, the early
      detection of Acanthamoeba would contribute significantly to disease management
      and selection of an appropriate anti-amoebic therapy. Recently, the loop-mediated
      isothermal amplification (LAMP) method has been applied to the clinical diagnosis
      of a range of infectious diseases. Here, we describe a rapid and efficient LAMP
      based method targeting Acanthamoeba 18S rDNA gene for the detection of
      Acanthamoeba using clinical ocular specimens in the diagnosis of AK. Acanthamoeba
      LAMP assays detected 11 different strains including all AK-associated species.
      The copy number detection limit for a positive signal was 10 DNA copies of 18S
      rDNA per reaction. No cross-reactivity with the DNA of fungi or other protozoa
      was observed. The sensitivity of LAMP assay was higher than those of Nelson
      primer PCR and JDP primer PCR. In the present study, LAMP assay based on directly
      heat-treated samples was found to be as efficient at detecting Acanthamoeba as
      DNA extracted using a commercial kit, whereas PCR was only effective when
      commercial kit-extracted DNA was used. This study showed that the devised
      Acanthamoeba LAMP assay could be used to diagnose AK in a simple, sensitive, and
      specific manner. 

PMID- 23864738
TI  - Proliferation of Toxoplasma gondii suppresses host cell autophagy.
AB  - Autophagy is a process of cytoplasmic degradation of endogenous proteins and
      organelles. Although its primary role is protective, it can also contribute to
      cell death. Recently, autophagy was found to play a role in the activation of
      host defense against intracellular pathogens. The aims of our study was to
      investigate whether host cell autophagy influences Toxoplasma gondii
      proliferation and whether autophagy inhibitors modulate cell survival. HeLa cells
      were infected with T. gondii with and without rapamycin treatment to induce
      autophagy. Lactate dehydrogenase assays showed that cell death was extensive at
      36-48 hr after infection in cells treated with T. gondii with or without
      rapamycin. The autophagic markers, LC3 II and Beclin 1, were strongly expressed
      at 18-24 hr after exposure as shown by Western blotting and RT-PCR. However, the
      subsequent T. gondii proliferation suppressed autophagy at 36 hr post-infection.
      Pre-treatment with the autophagy inhibitor, 3-methyladenine (3-MA), down
      regulated LC3 II and Beclin 1. The latter was also down-regulated by calpeptin, a
      calpain inhibitor. Monodansyl cadaverine (MDC) staining detected numerous
      autophagic vacuoles (AVs) at 18 hr post-infection. Ultrastructural observations
      showed T. gondii proliferation in parasitophorous vacuoles (PVs) coinciding with
      a decline in the numbers of AVs by 18 hr. FACS analysis failed to confirm the
      presence of cell apoptosis after exposure to T. gondii and rapamycin. We
      concluded that T. gondii proliferation may inhibit host cell autophagy and has an
      impact on cell survival. 

PMID- 23864739
TI  - Age-related CD4(+)CD25(+)Foxp3(+) regulatory T-cell responses during Plasmodium
      berghei ANKA infection in mice susceptible or resistant to cerebral malaria.
AB  - Different functions have been attributed to CD4(+)CD25(+)Foxp3(+) regulatory T
      cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg
      response and pro- and anti-inflammatory cytokines during infection with
      Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old)
      C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the
      middle-aged mice were resistant to CM and succumbed to hyperparasitemia and
      severe anemia. The levels of pro-inflammatory cytokines, such as TNF-alpha, in
      young CM-susceptible mice were markedly higher than in middle-aged CM-resistant
      mice. An increased absolute number of Tregs 3-5 days post-inoculation, co
      occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant
      mice but not in young CM-susceptible mice. Our findings suggest that Treg
      proliferation might be associated with the suppression of excessive pro
      inflammatory Th1 response during early malaria infection, leading to resistance
      to CM in the middle-aged mice, possibly in an IL-10-dependent manner. 

PMID- 23864740
TI  - Therapeutic potential of myrrh and ivermectin against experimental Trichinella
      spiralis infection in mice.
AB  - Trichinosis is a parasitic zoonosis caused by the nematode Trichinella spiralis.
      Anthelmintics are used to eliminate intestinal adults as well as tissue-migrating
      and encysted larvae. This study aimed to investigate the effects of ivermectin
      and myrrh obtained from the aloe-gum resin of Commiphora molmol on experimental
      trichinosis. Ninety albino mice were orally infected with 300 T. spiralis larvae.
      Drugs were tested against adult worms at day 0 and day 5 and against encysted
      larvae on day 15 and day 35 post-infection (PI). Mature worms and encysted larvae
      were counted in addition to histopathological examination of muscle specimens.
      Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total
      protein, albumin, globulin, urea, and creatinine values were estimated.
      Significant reductions in mean worm numbers were detected in ivermectin treated
      mice at day 0 and day 5 PI achieving efficacies of 98.5% and 80.0%, while
      efficacies of myrrh in treated mice were 80.7% and 51.5%, respectively. At days
      15 and 35 post-infection, ivermectin induced significant reduction in encysted
      larval counts achieving efficacies of 76.5% and 54.0%, respectively, while myrrh
      efficacies were 76.6% and 35.0%, respectively. AST, ALT, urea, and creatinine
      levels were reduced, while total proteins were increased in response to both
      treatments compared to their values in the infected non-treated mice. Ivermectin
      use for controlling T. spiralis could be continued. Myrrh was effective and could
      be a promising drug against the Egyptian strains of T. spiralis with results
      nearly comparable to ivermectin. 

PMID- 23864741
TI  - Hyperendemicity of Haplorchis taichui infection among riparian people in Saravane
      and Champasak province, Lao PDR.
AB  - In this study, we found that Haplorchis taichui, a heterophyid intestinal fluke,
      is highly prevalent, with heavy worm loads, among riparian people in Saravane and
      Champasak province, Lao PDR. Fecal specimens were collected from 1,460 people
      (717 men and 743 women) in 12 riparian (Mekong river) districts and were examined
      by the Kato-Katz fecal smear technique. The overall helminth egg positive rate
      was 78.8% and 66.4% in Saravane and Champasak province, respectively. The
      positive rate for small trematode eggs (STE), which included H. taichui and other
      heterophyids, Opisthorchis viverrini, and lecithodendriids, was 69.9% and 46.3%
      in Saravane and Champasak province, respectively. To obtain adult flukes, 30 STE
      positive people were treated with 40 mg/kg praziquantel and then purged. Whole
      diarrheic stools were collected 4-5 times for each person and searched for fluke
      specimens using a stereomicroscope. Mixed infections with various species of
      trematodes (H. taichui, Haplorchis pumilio, O. viverrini, Prosthodendrium
      molenkampi, Centrocestus formosanus, and Echinochasmus japonicus) and a species
      of cestode (Taenia saginata) were found. However, the worm load was exceptionally
      high for H. taichui compared with other trematode species, with an average of
      21,565 and 12,079 specimens per infected person in Saravane and Champasak
      province, respectively, followed by H. pumilio (41.9 and 22.5, respectively) and
      O. viverrini (9.4 and 1.5, respectively). These results show that diverse species
      of intestinal and liver flukes are prevalent among riparian people in Saravane
      and Champasak province, Lao PDR, with H. taichui being the exceptionally dominant
      species. 

PMID- 23864742
TI  - Serodiagnosis of echinococcosis by ELISA using cystic fluid from Uzbekistan
      sheep.
AB  - According to increase of travel, the cases of imported echinococcosis have been
      increasing in Korea. The present study was undertaken to develop a serodiagnostic
      system for echinococcosis in Korea. For diagnosis of echinococcosis, the fluid of
      Echinococcus granulosus hydatid cysts was collected from naturally infected sheep
      in Uzbekistan. Also serum samples of infected patients who were surgically
      confirmed were collected in a hospital in Tashkent, Uzbekistan. According to the
      absorbance of 59 echinococcosis positive and 39 negative control serum samples,
      the cut-off value was determined as 0.27. The sensitivity and specificity of
      ELISA with hydatid fluid antigen were 91.5% and 96%, respectively. The antigen
      cross-reacted with the serum of some cysticercosis or clonorchiasis patients.
      However, immunoblot analysis on the cystic fluid recognized antigenic proteins of
      7-, 16-, and 24-kDa bands in their dominant protein quantity and strong blotting
      reactivity. In conclusion, the present ELISA system using hydatid cyst fluid
      antigen from Uzbekistan sheep is sensitive and specific for diagnosis of
      echinococcosis cases. 

PMID- 23864743
TI  - Seasonal distribution of ticks in four habitats near the demilitarized zone,
      Gyeonggi-do (Province), Republic of Korea.
AB  - This study describes the seasonal distribution of larvae, nymph, and adult life
      stages for 3 species of ixodid ticks collected by tick drag and sweep methods
      from various habitats in the Republic of Korea (ROK). Grasses less than 0.5 m in
      height, including herbaceous and crawling vegetation, and deciduous, conifer, and
      mixed forests with abundant leaf/needle litter were surveyed at United States
      (US) and ROK operated military training sites and privately owned lands near the
      demilitarized zone from April-October, 2004 and 2005. Haemaphysalis longicornis
      Neumann adults and nymphs were more frequently collected from April-August, while
      those of Haemaphysalis flava Neumann and Ixodes nipponensis Kitaoka and Saito
      were collected more frequently from April-July and again during October. H.
      longicornis was the most frequently collected tick in grass habitats (98.9%),
      while H. flava was more frequently collected in deciduous (60.2%) and conifer
      (57.4%) forest habitats. While more H. flava (54.1%) were collected in mixed
      forest habitats than H. longicornis (35.2%), the differences were not
      significant. I. nipponensis was more frequently collected from conifer (mean 8.8)
      compared to deciduous (3.2) and mixed (2.4) forests. 

PMID- 23864744
TI  - Screening and molecular cloning of a protective antigen from the midgut of
      Haemaphysalis longicornis.
AB  - Vaccination is considered a promising alternative for controlling tick
      infestations. Haemaphysalis longicornis midgut proteins separated by SDS-PAGE and
      transferred to polyvinylidene difluoride (PVDF) membrane were screened for
      protective value against bites. The western blot demonstrated the immunogenicity
      of 92 kDa protein (P92). The analysis of the P92 amino acid sequence by LC-MS/MS
      indicated that it was a H. longicornis paramyosin (Hl-Pmy). The full lenghth cDNA
      of Hl-Pmy was obtained by rapid amplification of cDNA ends (RACE) which consisted
      of 2,783 bp with a 161 bp 3' untranslated region. Sequence alignment of tick
      paramyosin (Pmy) showed that Hl-Pmy shared a high level of conservation among
      ticks. Comparison with the protective epitope sequence of other invertebrate Pmy,
      it was calculated that the protective epitope of Hl-Pmy was a peptide
      (LEEAEGSSETVVEMNKKRDTE) named LEE, which was close to the N-terminal of Hl-Pmy
      protein. The secondary structure analysis suggested that LEE had non-helical
      segments within an alpha-helical structure. These results provide the basis for
      developing a vaccine against biting H. longicornis ticks. 

PMID- 23864745
TI  - Fatal Balamuthia amebic encephalitis in a healthy child: a case report with
      review of survival cases.
AB  - Balamuthia mandrillaris is one of the 4 amebas in fresh water and soil that cause
      diseases in humans. Granulomatous amebic encephalitis (GAE), caused by B.
      mandrillaris, is a rare but life-threatening condition. A 4-year-old, previously
      healthy, Thai girl presented with progressive headache and ataxia for over a
      month. Neuroimaging studies showed an infiltrative mass at the right cerebellar
      hemisphere mimicking a malignant cerebellar tumor. The pathological finding after
      total mass removal revealed severe necrotizing inflammation, with presence of
      scattered amebic trophozoites. Cerebrospinal fluid (CSF) obtained from lumbar
      puncture showed evidence of non-specific inflammation without identifiable
      organisms. A combination of pentamidine, sulfasalazine, fluconazole, and
      clarithromycin had been initiated promptly before PCR confirmed the diagnosis of
      Balamuthia amebic encephalitis (BAE). The patient showed initial improvement
      after the surgery and combined medical treatment, but gradually deteriorated and
      died of multiple organ failure within 46 days upon admission despite early
      diagnosis and treatment. In addition to the case, 10 survivors of BAE reported in
      the PubMed database were briefly reviewed in an attempt to identify the possible
      factors leading to survival of the patients diagnosed with this rare disease. 

PMID- 23864746
TI  - Gnathostoma spinigerum infection in the upper lip of a Korean woman: an
      autochthonous case in Korea.
AB  - Autochthonous human gnathostomiasis had never been reported in the Republic of
      Korea. We report here a case of Gnathostoma spinigerum infection in a 32-year-old
      Korean woman, presumed to have been infected via an indigenous route. The patient
      had experienced a painful migratory swelling near the left nasolabial fold area
      of the face for a year, with movement of the swelling to the mucosal area of the
      upper lip 2 weeks before surgical removal of the lesion. Histopathological
      examinations of the extracted tissue revealed inflammation with heavy
      eosinophilic infiltrations and sections of a nematode suggestive of a Gnathostoma
      sp. larva. The larva characteristically revealed about 25 intestinal cells with
      multiple (3-6) nuclei in each intestinal cell consistent with the 3rd-stage larva
      of G. spinigerum. The patient did not have any special history of travel abroad
      except a recent trip, 4 months before surgery, to China where she ate only cooked
      food. The patient is the first recorded autochthonous case of G. spinigerum
      infection in Korea. 

PMID- 23864747
TI  - A giant hydatid cyst in the interventricular septum with papillary muscle
      involvement.
AB  - We present here a 44-year-old male patient with hydatid disease who was referred
      to our hospital due to dyspnea and chest pain for the last 2 month before
      admission. Using echocardiography and contrast-enhanced computed tomography the
      heart hydatid was diagnosed. However, hydatid disease of the interventricular
      septum is rare; particularly, the involvement of mitral apparatus with mitral
      regurgitation (MR) is an exceptionally rare presentation. Early diagnosis and an
      integrated treatment strategy are crucial. Surgical excision was performed and
      the patient had an uneventful recovery and follow-up at 3 months. 

PMID- 23864748
TI  - Cryptosporidium hominis infection diagnosed by real-time PCR-RFLP.
AB  - There are approximately 20 known species of the genus Cryptosporidium, and among
      these, 8 infect immunocompetent or immunocompromised humans. C. hominis and C.
      parvum most commonly infect humans. Differentiating between them is important for
      evaluating potential sources of infection. We report here the development of a
      simple and accurate real-time PCR-based restriction fragment length polymorphism
      (RFLP) method to distinguish between C. parvum and C. hominis. Using the CP2 gene
      as the target, we found that both Cryptosporidium species yielded 224 bp
      products. In the subsequent RFLP method using TaqI, 2 bands (99 and 125 bp)
      specific to C. hominis were detected. Using this method, we detected C. hominis
      infection in 1 of 21 patients with diarrhea, suggesting that this method could
      facilitate the detection of C. hominis infections. 

PMID- 23864749
TI  - Prevalence of Toxoplasma gondii infection in household cats in Korea and risk
      factors.
AB  - Several epidemiological surveys have reported the prevalence of Toxoplasma gondii
      infection in stray cats in Korea, but little information is available on T.
      gondii infection in household cats. The aim of the present study was to assess
      the prevalence and risk factors of T. gondii infection among household cats
      reared in Seoul, Korea. A total of 474 blood samples were collected from
      clinically healthy household cats. All samples were tested using ELISA and PCR.
      The risk factor analysis was based on a questionnaire filled out by the owners.
      The overall positive rate for ELISA and PCR assays was 2.2% (10/437) and 2.1%
      (10/474), respectively. With regard to the origin of cats, the positive rates
      among cats adopted from the animal shelter and veterinary clinic for stray cats
      were significantly different (P<0.05). Our study demonstrated that the positive
      rate of T. gondii infection in household cats was low and that this low
      prevalence was assumed to be associated with keeping the cats indoors and
      restriction of eating raw food and uncooked meat. Therefore, we suggest that the
      owners check the origin of the cats prior to adoption to prevent infection of
      other animals, including humans. 

PMID- 23864750
TI  - Prevalence and genetic characterization of Toxoplasma gondii in house sparrows
      (Passer domesticus) in Lanzhou, China.
AB  - The prevalence of Toxoplasma gondii infection in birds has epidemiological
      significance because birds are indeed considered as a good indicator of
      environmental contamination by T. gondii oocysts. In this study, the prevalence
      of T. gondii in 313 house sparrows in Lanzhou, northwestern China was assayed by
      the modified agglutination test (MAT). Antibodies to T. gondii were positive in
      39 (12.46%) of 313 samples (MAT titer >= 1:5). Tissues of heart, brain, and lung
      from the 39 seropositive house sparrows were tested for T. gondii DNA, 11 of
      which were found to be positive for the T. gondii B1 gene by PCR amplification.
      These positive DNA samples were typed at 9 genetic markers, including 8 nuclear
      loci, i.e., SAG1, 5'- and 3'-SAG2, alternative SAG2, SAG3, GRA6, L358, PK1, c22-8
      and an apicoplast locus Apico. Of them, 4 isolates were genotyped with complete
      data for all loci, and 2 genotypes (Type II variants; ToxoDB #3 and a new
      genotype) were identified. These results showed that there is a potential risk
      for human infection with T. gondii in this region. To our knowledge, this is the
      first report of T. gondii seroprevalence in house sparrows in China. 

PMID- 23864751
TI  - Morphologic and genetic evidence for mixed infection with two Myxobolus species
      (Myxozoa: Myxobolidae) in gray mullets, Mugil cephalus, from Korean waters.
AB  - The present study was performed to trace the decisive evidence for mixed
      infection of 2 Myxobolus species, M. episquamalis and Myxobolus sp., in the gray
      mullet, Mugil cephalus, from Korean waters. Mullets with whitish cyst-like
      plasmodia on their scales were collected near a sewage plant in Yeosu, southern
      part of Korea, in 2009. The cysts were mainly located on scales and also found in
      the intestine. The spores from scales were oval in a frontal view, tapering
      anteriorly to a blunt apex, and measured 7.2 um (5.8-8.0) in length and 5.3 um
      (4.7-6.1) in width. Two polar capsules were pyriform and extended over the
      anterior half of the spore, measuring 3.5 um (2.3-4.8) in length and 2.0 um (1.5
      2.2) in width. In contrast, the spores from the intestine were ellipsoidal, 10.4
      um (9.0-11.9) in length and 8.4 um (7.3-10.1) in width. The polar capsules were
      pyriform but did not extend over the anterior half of the spore, 3.7 um (2.5-4.5)
      in length and 2.2 um (1.8-2.9) in width. The nucleotide sequences of the 18S rDNA
      gene of the 2 myxosporean spores from scales and intestine showed 88.1% identity
      to each other and 100% identity with M. episquamalis and 94.5% identity with M.
      spinacurvatura from mullet, respectively. By the above findings, it is first
      confirmed that mullets from the Korean water are infected with 2 myxosporean
      species, M. episquamalis and Myxobolus sp. 

PMID- 23864752
TI  - Prevalence of Dirofilaria immitis in dogs in Shenyang, Northeastern China.
AB  - In the present study, we first report the seroprevalence of Dirofilaria immitis
      in dogs in Shenyang, northeastern China. Sera from 528 randomly selected dogs
      were examined for D. immitis antigen using SNAP(r)4Dx test kit; 12.7% tested
      showed seropositive. No significant difference of infection was observed in
      different genders and breeds (P>0.05), but the difference was significant in
      different age groups and rearing conditions (P<0.05). The result suggested that
      the risk of exposure to D. immitis in dogs is high in Shenyang, and should be
      given attention. 

PMID- 23864753
TI  - Spargana in a weasel, Mustela sibirica manchurica, and a wild boar, Sus scrofa,
      from Gangwon-do, Korea.
AB  - To know the status of sparganum (plerocercoid of Spirometra erinacei) infection
      in the Korean wild life, several species of wild animals were captured in Gangwon
      do and examined for their status of infection with spargana. From February to
      December 2011, a total of 62 wild boars, 5 badgers, 1 weasel, 1 Siberian
      chipmunk, and 53 wild rodents were captured, and their whole muscles were
      examined with naked eyes for the presence of spargana worms. From the weasel and
      1 wild boar, a total of 5 spargana specimens were extracted. The weasel was for
      the first time recorded as an intermediate or paratenic/transport host of S.
      erinacei in Korea, and both the weasel (Mustela sibirica manchurica) and wild
      boar (Sus scrofa) were added to the list of wild animals carrying spargana. 

PMID- 23864754
TI  - Infection status of hydatid cysts in humans and sheep in Uzbekistan.
AB  - Uzbekistan is endemic of cystic echinococcosis (CE). In order to estimate
      endemicity of CE, we collected data from emergency surgery due to CE in 2002-2010
      and also investigated the prevalence of hydatid cysts in the liver and lungs of
      sheep at an abattoir in Uzbekistan from July 2009 to June 2010. In 14 emergency
      hospitals, 8,014 patients received surgical removal or drainage of CE during 2002
      2010, and 2,966 patients were found in 2010. A total of 22,959 sheep were grossly
      examined of their liver and lungs, and 479 (2.1%) and 340 (1.5%) of them were
      positive for the cyst in the liver and lungs, respectively. Echinococcus
      granulosus is actively transmitted both to humans and sheep, and CE is a zoonotic
      disease of public health priority in Uzbekistan. 

PMID- 23864755
TI  - RTOG 0631 Phase II/III Study of Image-Guided Stereotactic Radiosurgery for
      Localized (1-3) Spine Metastases: Phase II Results.
AB  - PURPOSE: The phase II component of RTOG 0631 assessed the feasibility and safety
      of spine radiosurgery (SRS) for localized spine metastases in a cooperative group
      setting. MATERIALS AND METHODS: Patients with 1-3 spine metastasis with a
      Numerical Rating Pain Scale (NRPS) score >= 5 received 16 Gy single fraction SRS.
      The primary endpoint was SRS feasibility: image-guidance RT (IGRT) targeting
      accuracy <= 2mm, target volume coverage > 90% of prescription dose, maintaining
      spinal cord dose constraints (10 Gy to <= 10% of the cord volume from 5-6mm above
      to 5-6mm below the target or absolute spinal cord volume < 0.35cc) and other
      normal tissue dose constraints. A feasibility success rate < 70% was considered
      unacceptable for continuation of the phase III component. Based on the one-sample
      exact binomial test with alpha=0.10 (1-sided), 41 patients were required. Acute
      toxicity was assessed using the National Cancer Institute Common Toxicity
      Criteria for Adverse Events, version 3.0. RESULTS: Sixty-five institutions were
      credentialed with spine phantom dosimetry and IGRT compliance. Forty-six patients
      were accrued, and 44 were eligible. There were 4 cervical, 21 thoracic and 19
      lumbar sites. Median NRPS was 7 at presentation. Final pre-treatment rapid review
      was approved in 100%. Accuracy of image-guided SRS targeting was in compliance
      with the protocol in 95%. The target coverage and spinal cord dose constraint
      were in accordance with the protocol requirements in 100% and 97%. Overall
      compliance for other normal tissue constraints was per protocol in 74%. There
      were no cases of grade 4-5 acute treatment-related toxicity. CONCLUSION: The
      phase II results demonstrate the feasibility and accurate use of SRS to treat
      spinal metastases, with rigorous quality control, in a cooperative group setting.
      The planned RTOG 0631 phase III component will proceed to compare pain relief and
      quality of life between SRS and external beam radiotherapy.

PMID- 23864756
TI  - An evaluation of neoadjuvant chemoradiotherapy for patients with resectable
      pancreatic ductal adenocarcinoma.
AB  - Aims. The aim of this study is to compare our results of preoperative
      chemotherapy followed by pancreaticoduodenectomy (PD) with those of surgery alone
      in patients with localized resectable pancreatic ductal adenocarcinoma (PDAC).
      Methods. Outcome data for 112 patients of resectable PDAC who received
      preoperative chemoradiotherapy followed by PD (group I) between January 2004 and
      April 2010 were retrospectively analyzed and were compared with selected 120
      patients who underwent PD alone (group II) in the same period. Results. Patients
      in group I had an incidence of locoregional recurrence of 17.1% compared to 30.8%
      in group II (P = 0.03). There were no statistically significant differences in
      postoperative morbidity (27.7% versus 30.8%) and mortality (2.67% versus 3.33%).
      The 1-, 2-, and 3-year survival rates were estimated at 82.1%, 54%, and 28%,
      respectively, with NCRT and 65.8%, 29.1%, and 10% without (P = 0.006).
      Nevertheless, preoperative chemotherapy did not reduce the 1-, 3-, and 5-year
      disease-free survival rates, which were estimated at 58%, 36.6%, and 12.5% with
      NCRT and 51.7%, 18.3%, and 7.5% without (P = 0.058). Conclusions. The treatment
      of NCRT followed by PD in patients with PDAC has a significantly lower rate of
      locoregional recurrence and a longer overall survival than those with surgery
      alone. 

PMID- 23864758
TI  - Assalaamu alaykum.

PMID- 23864757
TI  - Assalaamu alaykum.

PMID- 23864759
TI  - Eliminate Second-hand Smoking from Islamic Campuses in North America.

PMID- 23864760
TI  - The Bioethical Concept of Life for Life in Judaism, Catholicism, and Islam:
      Abortion When the Mother's Life is in Danger.
AB  - Modern secular bioethics has focused on developing a set of universal principles
      to guide clinical decision making. However, this ignores the important role of
      religion in resolving bioethical questions. It is imperative that health-care
      providers understand these belief systems in order to traverse value conflicts
      and provide the highest quality care to a diverse population. This paper focuses
      on the process of bioethical deliberation in Judaism, Catholicism, and Islam.
      Abortion is normatively prohibited in each faith and through examining how each
      ethical code allows for abortion when the mother's life is in peril due to the
      fetus, we highlight the value of unborn life in each faith. Orthodox Judaism uses
      the concept of rodef, or pursuer, to permit abortion in this scenario,
      Catholicism uses the moral concept of "double effect," while Islamic law cites
      the maqasid, higher objectives of the law, to permit abortion in this scenario. 

PMID- 23864761
TI  - Mental health issues of muslim americans.
AB  - The underpinning of all research leading to various schools of thought in the
      field of psychiatry and psychology is without doubt a product of Western
      professionals who represent the religio-cultural traditions, historical symbols,
      and narratives of Western society. Also, the major schools of psychotherapy
      emerged during an era of individualism and logical positivism reflecting the
      religious, ethical, and cultural heritage that has shaped the modern Western
      society. Consequently, the methods and techniques developed in the West may not
      be always suitable and effective for Muslim Americans. To respond to the growing
      needs of psychiatric problems encountered by Muslim Americans, many community
      social service centers have been established in the United States during the past
      two decades. We now have a growing body of research data suggesting how to tailor
      our field to the specific needs of this population. We will discuss what kind of
      emotional and psychiatric problems are most prevalent in Muslim Americans and
      explain the therapeutic approaches mental health professionals have used and the
      treatment strategies which have been found effective in the psychosocial
      rehabilitation of Muslim Americans. 

PMID- 23864762
TI  - The muslim physician and the ethics of medicine.
AB  - Virtuous physicians seem to have become a rarity in modern day medical practice.
      Many patients and physicians feel that the profession of medicine is not living
      up to its own standards and expectations. It is the contention of the author that
      the Muslim physician, guided by the two primary sources of Islamic Law, the
      Qur'an and the Sunna, will possess the necessary character traits of a good
      physician. In this article I argue that the Muslim physician who abides by the
      Qur'an will live a contented life, will be trusted by his/her patients and
      community, and will be in line with the recently enacted Western principles of
      medical ethics. 

PMID- 23864764
TI  - Dr. Humayun chaudhry: a public health policy advocate.

PMID- 23864763
TI  - The muslim community center clinic: a Maryland safety net clinic, achievements
      and challenges.
AB  - The Muslim Community Center (MCC) is located in Silver Spring, Maryland, which is
      about 13 miles from the United States Capitol in Washington, D.C. The clinic is a
      part of the Primary Care Coalition, a network of 13 clinics that provide medical
      care to low-income uninsured residents of Montgomery County, Maryland. The clinic
      is open six days a week from 9 a.m. to 5 p.m. to provide free medical care to
      people age 18 or older without medical coverage, regardless of race, religion,
      country of origin, creed, ethnicity, or sex. Since its inception on June 15,
      2003, it has provided more than 18,000 patient visits. The Muslim Community
      Center Medical Clinic is the second largest Muslim-run charity clinic in the
      United States. 

PMID- 23864765
TI  - TLR2 and TLR4 in the brain injury caused by cerebral ischemia and reperfusion.
AB  - Brain injury caused by cerebral ischemia/reperfusion is a complicated
      pathophysiological course, in which inflammation is thought to play an important
      role. Toll-like receptors are a type of transmembrane proteins, which can
      recognize either exogenous pathogen-associated molecular patterns or endogenous
      stress or damage-associated molecular patterns in the innate immune system and
      initiate inflammatory responses. Among Toll-like receptors, TLR2 and TLR4 are
      found to be more important than others in the pathological progression of
      cerebral injury due to ischemia and reperfusion. This review will focus on the
      biological characteristics and functions of TLR2 and TLR4 and their downstream
      signal pathways.

PMID- 23864766
TI  - The causative pathogen determines the inflammatory profile in cerebrospinal fluid
      and outcome in patients with bacterial meningitis.
AB  - BACKGROUND: The brain's inflammatory response to the infecting pathogen
      determines the outcome of bacterial meningitis (BM), for example, the associated
      mortality and the extent of brain injury. The inflammatory cascade is initiated
      by the presence of bacteria in the cerebrospinal fluid (CSF) activating resident
      immune cells and leading to the influx of blood derived leukocytes. To elucidate
      the pathomechanisms behind the observed difference in outcome between different
      pathogens, we compared the inflammatory profile in the CSF of patients with BM
      caused by Streptococcus pneumonia (n = 14), Neisseria meningitidis (n = 22), and
      Haemophilus influenza (n = 9). METHODS: CSF inflammatory parameters, including
      cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were
      assessed in a cohort of patients with BM from Burkina Faso. RESULTS: Pneumococcal
      meningitis was associated with significantly higher CSF concentrations of IFN
      gamma , MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a
      fatal outcome, levels of TNF-alpha, IL-1 beta, IL-1RA, IL-6, and TGF-alpha were
      significantly higher. CONCLUSION: The signature of pro- and anti-inflammatory
      mediators and the intensity of inflammatory processes in CSF are determined by
      the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis
      being associated with a higher case fatality rate than meningitis caused by N.
      meningitidis or H. influenzae.

PMID- 23864767
TI  - Association of CFH and CFB gene polymorphisms with retinopathy in type 2 diabetic
      patients.
AB  - OBJECTIVES: The complement system is a key component of innate immunity and has
      been implicated in the pathogenesis of diabetic retinopathy (DR). This study
      aimed at investigating whether polymorphisms of two genes in the complement
      pathway, complement factor H (CFH) and complement factor B (CFB), are associated
      with DR. METHODS: 552 well-defined subjects with type 2 diabetes, consisting of
      277 DR patients and 275 diabetic controls, were recruited. Four Tag-SNPs
      rs1048709, rs537160, rs4151657, and rs2072633 in CFB and rs800292 (I62V) in CFH
      were examined using TaqMan Genotyping Assays. RESULTS: There were significant
      increases in the frequencies of A allele and AA genotype for rs1048709 in DR
      patients compared with diabetic controls (P(corr) = 0.035, OR = 1.42; P(corr) =
      0.02, OR = 2.27, resp.): meanwhile, significant decreases in the frequencies of A
      allele and AA genotype for rs800292 were observed in DR patients compared with
      diabetic controls (P(corr) = 0.04, OR = 0.72; P(corr) = 0.015, OR = 0.51, resp.).
      Joint effect of these two loci was also identified. Moreover, rs800292/AA
      genotype was found to be related with delayed progression to DR. CONCLUSIONS: CFH
      rs800292 and CFB-rs1048709 are associated with the presence of DR, which
      strengthens the concept that complement system plays an important role in the
      pathogenesis of DR.

PMID- 23864768
TI  - The effect of anti-inflammatory and antimicrobial herbal remedy PADMA 28 on
      immunological angiogenesis and granulocytes activity in mice.
AB  - PADMA 28 is a herbal multicompound remedy that originates from traditional
      Tibetan medicine and possesses anti-inflammatory, antioxidant, antimicrobial,
      angioprotecting, and wound healing properties. The aim of the present study was
      to evaluate the influence of this remedy on immunological angiogenesis and
      granulocytes metabolic activity in Balb/c mice. Mice were fed daily, for seven
      days, with 5.8 mg of PADMA (calculated from recommended human daily dose) or
      0.085 mg (dose in the range of active doses of other herbal extracts studied by
      us previously). RESULTS: Highly significant increase of newly formed blood
      vessels number in ex vivo cutaneous lymphocyte-induced angiogenesis test (LIA)
      after grafting of Balb/c splenocytes from both dosage groups to F1 hybrids
      (Balb/c * C3H); increase of blood lymphocytes and granulocytes number only in
      mice fed with lower dose of remedy; and significant suppression of metabolic
      activity (chemiluminescence test) of blood granulocytes in mice fed with higher
      dose of PADMA. CONCLUSION: PADMA 28 behaves as a good stimulator of physiological
      angiogenesis, but for this purpose it should be used in substantially lower doses
      than recommended by producers for avoiding the deterioration of granulocyte
      function.

PMID- 23864769
TI  - Posttranslational nitration of tyrosine residues modulates glutamate transmission
      and contributes to N-methyl-D-aspartate-mediated thermal hyperalgesia.
AB  - Activation of the N-methyl-D-aspartate receptor (NMDAR) is fundamental in the
      development of hyperalgesia. Overactivation of this receptor releases superoxide
      and nitric oxide that, in turn, forms peroxynitrite (PN). All of these events
      have been linked to neurotoxicity. The receptors and enzymes involved in the
      handling of glutamate pathway--specifically NMDARs, glutamate transporter, and
      glutamine synthase (GS)--have key tyrosine residues which are targets of the
      nitration process causing subsequent function modification. Our results
      demonstrate that the thermal hyperalgesia induced by intrathecal administration
      of NMDA is associated with spinal nitration of GluN1 and GluN2B receptor
      subunits, GS, that normally convert glutamate into nontoxic glutamine, and
      glutamate transporter GLT1. Intrathecal injection of PN decomposition catalyst
      FeTM-4-PyP(5+) prevents nitration and overall inhibits NMDA-mediated thermal
      hyperalgesia. Our study supports the hypothesis that nitration of key proteins
      involved in the regulation of glutamate transmission is a crucial pathway used by
      PN to mediate the development and maintenance of NMDA-mediated thermal
      hyperalgesia. The broader implication of our findings reinforces the notion that
      free radicals may contribute to various forms of pain events and the importance
      of the development of new pharmacological tool that can modulate the glutamate
      transmission without blocking its actions directly.

PMID- 23864771
TI  - The role of alcohol price in young adult drinking cultures in Scotland.
AB  - Minimum Unit Pricing (MUP) is one of the Scottish Government's key policy options
      to reduce alcohol consumption and related harm. Although strongly evidenced for
      efficacy in reducing headline population level consumption, efficacy in changing
      the role of alcohol in Scottish culture is unknown. Questions remain as to how
      MUP will play across population subgroups with different sensitivities to price.
      In this paper we explore the views of the young adult population and situate the
      influence of price paid for alcohol alongside broader cultural drivers of
      consumption. Qualitative data from two studies investigating the role of alcohol
      in the transition to adulthood from 130 participants (aged 16-30) are analysed to
      situate the influence of price paid in shaping drinking styles and practices.
      Findings highlight how considerations of price paid for alcohol compete with non
      financial considerations associated with choosing to drink excessively,
      moderately or not at all. Two broad categories of response to potential price
      increases were anticipated by drinkers which indicate that young adults are not a
      homogenous group in relation to price sensitivity. These differences highlight
      the potential for variation in subgroup responses to a pricing policy conceived
      to be effective at a population level.

PMID- 23864770
TI  - Cytokine patterns in brain tumour progression.
AB  - Inflammation represents the immune system response to external or internal
      aggressors such as injury or infection in certain tissues. The body's response to
      cancer has many parallels with inflammation and repair; the inflammatory cells
      and cytokines present in tumours are more likely to contribute to tumour growth,
      progression, and immunosuppression, rather than in building an effective
      antitumour defence. Using new proteomic technology, we have investigated serum
      profile of pro- (IL-1beta , IL-6, IL-8, IL-12, GM-CSF, and TNF-alpha ) and anti
      inflammatory cytokines (IL-4, IL-10), along with angiogenic factors (VEGF, bFGF)
      in order to assess tumoural aggressiveness. Our results indicate significant
      dysregulation in serum levels of cytokines and angiogenic factors, with over
      threefold upregulation of IL-6, IL-1beta , TNF-alpha , and IL-10 and up to
      twofold upregulation of VEGF, FGF-2, IL-8, IL-2, and GM-CSF. These molecules are
      involved in tumour progression and aggressiveness, and are also involved in a
      generation of disease associated pain.

PMID- 23864772
TI  - Cellular and molecular basis of chronic constipation: taking the
      functional/idiopathic label out.
AB  - In recent years, the improvement of technology and the increase in knowledge have
      shifted several strongly held paradigms. This is particularly true in
      gastroenterology, and specifically in the field of the so-called "functional" or
      "idiopathic" disease, where conditions thought for decades to be based mainly on
      alterations of visceral perception or aberrant psychosomatic mechanisms have, in
      fact, be reconducted to an organic basis (or, at the very least, have shown one
      or more demonstrable abnormalities). This is particularly true, for instance, for
      irritable bowel syndrome, the prototype entity of "functional" gastrointestinal
      disorders, where low-grade inflammation of both mucosa and myenteric plexus has
      been repeatedly demonstrated. Thus, researchers have also investigated other
      functional/idiopathic gastrointestinal disorders, and found that some organic
      ground is present, such as abnormal neurotransmission and myenteric plexitis in
      esophageal achalasia and mucosal immune activation and mild eosinophilia in
      functional dyspepsia. Here we show evidence, based on our own and other authors'
      work, that chronic constipation has several abnormalities reconductable to
      alterations in the enteric nervous system, abnormalities mainly characterized by
      a constant decrease of enteric glial cells and interstitial cells of Cajal (and,
      sometimes, of enteric neurons). Thus, we feel that (at least some forms of)
      chronic constipation should no more be considered as a functional/idiopathic
      gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.

PMID- 23864773
TI  - Systematic review of surgical resection vs radiofrequency ablation for
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) represents one of the most common neoplasms
      worldwide. Surgical resection and local ablative therapies represent the most
      frequent first lines therapies adopted when liver transplantation can not be
      offered or is not immediately accessible. Hepatic resection (HR) is currently
      considered the most curative strategy, but in the last decade local ablative
      therapies have started to obtain satisfactory results in term of efficacy and, of
      them, radiofrequency ablation (RFA) is considered the reference standard. An
      extensive literature review, from the year 2000, was performed, focusing on
      results coming from studies that directly compared HR and RFA. Qualities of the
      studies, characteristics of patients included, and patient survival and
      recurrence rates were analyzed. Except for three randomized controlled trials
      (RCT), most studies are affected by uncertain methodological approaches since
      surgical and ablated patients represent different populations as regards clinical
      and tumor features that are known to affect prognosis. Unfortunately, even the
      available RCTs report conflicting results. Until further evidences become
      available, it seems reasonable to offer RFA to very small HCC (< 2 cm) with no
      technical contraindications, since in this instance complete necrosis is most
      likely to be achieved. In larger nodules, namely > 2 cm and especially if > 3 cm,
      and/or in tumor locations in which ablation is not expected to be effective or
      safe, surgical removal is to be preferred. 

PMID- 23864774
TI  - Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer:
      clinico-pathogenic aspects.
AB  - Toll-like receptors (TLRs) recognize specific motifs which are frequently present
      in bacteria, fungi, prokaryotes and viruses. Amongst TLRs, TLR9 can be activated
      by such bacterial or viral DNA fragments, immunoglobulin-DNA complexes or
      synthetic oligonucleotides, which all contain unmethylated cytosine-guanine
      nucleotide sequences (CpGs). Emerging data indicate that TLR9 signaling has a
      role in, and may influence, colorectal carcinogenesis and colonic inflammation.
      CpGs are classified into three groups according to their influence on both the
      antigen-specific humoral- and cellular immunity, and the production of type 1
      interferons and proinflammatory cytokines. TLR9 activation via CpGs may serve as
      a new therapeutic target for several cancerous and various inflammatory
      conditions. Due to its probable anti-cancer effects, the application
      possibilities of TLR9-signaling modulation may be extremely diverse even in
      colorectal tumors. In this review we aimed to summarize the current knowledge
      about TLR-signaling in the pathogenesis and therapy of inflammatory bowel
      diseases and colorectal cancer. Due to the species-specific differences in TLR9
      expression, however, one must be careful in translating the animal model data
      into the human system, because of the differences between CpG
      oligodeoxynucleotide-responsive cells. TLR9 agonist DNA-based immunomodulatory
      sequences could also represent a promising therapeutic alternative in systemic
      inflammatory conditions and chronic colonic inflammations as their side effects
      are not significant. 

PMID- 23864775
TI  - Hugl-1 induces apoptosis in esophageal carcinoma cells both in vitro and in vivo.
AB  - AIM: To determine whether the human giant larvae homolog 1 gene (Hugl
      1/Llg1/Lgl1) exerts tumor suppressor effects in esophageal cancer. METHODS: We
      constructed a Hugl-1 expression plasmid, pEZ-M29-Hugl1, for gene transfection. We
      transfected the pEZ-M29-Hugl1 plasmid into Eca109 esophageal cancer cell lines
      with Lipofectamine 2000 to overexpress Hugl-1. Real-time reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting were performed to
      determine the effects of the plasmid on Hugl-1 expression. In vitro cell
      proliferation and apoptosis were examined separately by cell counting Kit-8 (CCK
      8) assay, flow cytometry, and Western blotting before and after the transfection
      of the plasmid into Eca109 cells. Cell cycle distribution was assessed with flow
      cytometry. The effect of Hugl-1 overexpressing on tumor growth in vivo was
      performed with a xenograft tumor model in nude mice. Expression of Hugl-1 in
      xenograft tumor was analyzed by immunohistochemistry. The transferase-mediated
      dUTP nick end-labeling (TUNEL) technique was performed to detect and quantitate
      apoptotic cell. RESULTS: The transfection efficiency was confirmed with real-time
      RT-PCR and Western blotting. Our results show that compared with control groups
      the mRNA levels and protein levels of Hugl-1 in pEZ-M29-Hugl1-treated group were
      remarkably increased (P < 0.05). The CCK-8 assay demonstrated that the growth of
      cells overexpressing Hugl-1 was significantly lower than control cells. Cell
      cycle distribution showed there was a G0/G1 cell cycle arrest in cells
      overexpressing Hugl-1 (64.09% +/- 3.14% vs 50.32% +/- 4.60%, 64.09% +/- 3.14% vs
      49.13% +/- 2.24%). Annexin V-fluorescein isothiocyanate revealed that apoptosis
      was significantly increased in cells overexpressing Hugl-1 compared with control
      group (17.33% +/- 4.76% vs 6.90% +/- 1.61%, 17.33% +/- 4.76% vs 6.27% +/- 0.38%).
      Moreover, we found that Hugl-1 changes the level of the anti-apoptotic protein
      Bcl-2 and the pro-apoptotic protein Bax and the activation of both caspase-3 and
      caspase-9. With a TUNEL assay, we found that Hugl-1 markedly increased the
      apoptosis rate of Eca109 cells in vivo (60.50% +/- 9.11% vs 25.00% +/- 12.25%).
      It was shown that Hugl-1 represents a significantly more effective tumor
      suppressor gene alone in a xenograft tumor mouse model. This data suggest that
      Hugl-1 inhibited tumor growth and induced cell apoptosis in vivo. CONCLUSION:
      These results suggest that Hugl-1 induces growth suppression and apoptosis in a
      human esophageal squamous cell carcinoma cell line both in vitro and in vivo.

PMID- 23864776
TI  - Effects of rhein on intestinal epithelial tight junction in IgA nephropathy.
AB  - AIM: To investigate the effects of rhein on intestinal epithelial tight junction
      proteins in rats with IgA nephropathy (IgAN). METHODS: Twenty-eight female
      Sprague-Dawley rats were randomly divided into four groups (7 per group):
      Control, IgAN, Rhein-treated, and Rhein-prevented. Bovine serum albumin,
      lipopolysaccharide and CCl4 were used to establish the rat model of IgA
      nephropathy. The Rhein-treated group was given rhein from week 7 until the rats
      were sacrificed. The Rhein-prevented group was given rhein from week 1. Animals
      were sacrificed at the end of week 10. We observed the changes in the intestinal
      epithelial tight junctions using transmission electron microscopy, and expression
      of intestinal epithelial tight junction proteins zona occludens protein (ZO)-1
      and occludin by immunofluorescence using laser confocal microscopy. Changes in
      mRNA and protein expression of ZO-1 and occludin were measured by reverse
      transcriptase polymerase chain reaction and Western blotting. The ratio of
      urinary lactulose/mannitol was measured by high performance liquid chromatography
      (HPLC) for assessing the intestinal permeability. RESULTS: In the control group,
      the tight junctions lied between epithelial cells on the top of the outer side of
      the cell membrane, and appeared in dense dotted crystal structures, the
      neighboring cells were binded tightly with no significant gap, and the tight
      junction protein ZO-1 and occludin were evenly distributed in the intestinal
      epithelial cells at the top of the junction. Compared with the control group, in
      the IgAN group, the structure of the tight junction became obscured and the
      dotted crystal structures had disappeared; the fluorescence of ZO-1 and occludin
      was uneven and weaker (5.37 +/- 1.27 vs 10.03 +/- 1.96, P < 0.01; 4.23 +/- 0.85
      vs 12.35 +/- 4.17, P < 0.01); the mRNA expression of ZO-1 and occludin decreased
      (0.42 +/- 0.19 vs 0.92 +/- 0.24, P < 0.01; 0.40 +/- 0.15 vs 0.97 +/- 0.25, P <
      0.01); protein expression of ZO-1 and occludin was decreased (0.85 +/- 0.12 vs
      1.98 +/- 0.43, P < 0.01; 0.72 +/- 0.15 vs 1.38 +/- 0.31, P < 0.01); and the ratio
      of urinary lactulose/mannitol increased (3.55 +/- 0.68 vs 2.72 +/- 0.21, P <
      0.01). In the Rhein-prevented and Rhein-treated groups, compared with the IgAN
      group, the intestinal epithelial tight junctions were repaired; fluorescence of
      ZO-1 and occludin was stronger (11.16 +/- 3.52 and 8.81 +/- 2.30 vs 5.37 +/-
      1.27, P < 0.01; 10.97 +/- 3.40 and 9.46 +/- 2.40 vs 4.23 +/- 0.85, P < 0.01);
      mRNA of ZO-1 and occludin increased (0.81 +/- 0.17 and 0.64 +/- 0.16 vs 0.42 +/-
      0.19, P < 0.01; 0.82 +/- 0.22 and 0.76 +/- 0.31 vs 0.40 +/- 0.15, P < 0.01);
      protein expression of ZO-1 and occludin was increased (2.07 +/- 0.41 and 1.57 +/-
      0.23 vs 0.85 +/- 0.12, P < 0.01; 1.34 +/- 0.21 and 1.15 +/- 0.17 vs 0.72 +/-
      0.15, P < 0.01); and the ratio of urinary lactulose/mannitol decreased (2.83 +/-
      0.43 and 2.87 +/- 0.18 vs 3.55 +/- 0.68, P < 0.01). CONCLUSION: Rhein can enhance
      the expression of ZO-1 and occludin, repair damaged tight junctions, and protect
      the intestinal barrier.

PMID- 23864777
TI  - Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on
      chronic liver failure.
AB  - AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells
      (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).
      METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients
      with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the
      First Affiliated Hospital of Medical College from January 2009 to June 2012. The
      ACLF patients were diagnosed according to the criteria recommended by The 19(th)
      Conference of the Asian Pacific Association for the Study of the Liver in 2009.
      Twenty healthy individuals with a similar gender and age structures to the two
      patient groups were also included as the normal controls (NC). Of the 50 ACLF
      patients, 28 were subsequently classified as non-survivors: 19 patients died from
      multi-organ failure, 3 underwent liver transplantation, and 6 discontinued
      therapy during follow-up because of financial reasons. The remaining 22 ACLF
      patients whose liver and anticoagulation function recovered to nearly normal
      levels within the next 6 mo were classified as survivors. The number of
      circulating Treg and Th17 cells was determined upon diagnosis and during the 8th
      week of follow-up through flow cytometry. RESULTS: The percentage of circulating
      Treg cells in the ACLF group was significantly higher than that in the CHB group
      (5.50% +/- 1.15% vs 3.30% +/- 1.13%, P < 0.01). The percentages of circulating
      Th17 cells in the ACLF and the CHB groups were significantly higher than that in
      the NC group (6.32% +/- 2.22% vs 1.56% +/- 0.44%, P < 0.01; 3.53% +/- 1.65% vs
      1.56% +/- 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell
      ratio was observed between the ACLF group and the CHB group (0.98 +/- 0.44 vs
      1.12 +/- 0.64, P = 0.991), whereas those in the two HBV infection groups were
      significantly lower than that in the NC group (1.85 +/- 1.22; both P < 0.01). The
      percentage of Treg cells in the survivors during the 8(th) week of follow-up was
      significantly lower than that during peak ACLF severity [total bilirubin (TBIL)
      peak] (3.45% +/- 0.97% vs 5.18% +/- 1.02%, P < 0.01). The percentage of Th17
      cells in survivors during the 8(th) week of follow-up was significantly lower
      than that during the peak TBIL (2.89% +/- 0.60% vs 5.24% +/- 1.46%; P < 0.01).
      The Treg cell to Th17 cell ratio during the 8(th) week of follow-up was
      significantly higher than that during the TBIL peak (1.22 +/- 0.36 vs 1.10 +/-
      0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during
      the follow-up phase of ACLF could maintain the immune system at a steady state,
      which favours good prognosis.

PMID- 23864779
TI  - Helicobacter pylori infection as a cause of iron deficiency anaemia of unknown
      origin.
AB  - AIM: To assess the aetiological role of Helicobacter pylori (H. pylori) infection
      in adult patients with iron-refractory or iron-dependent anaemia of previously
      unknown origin. METHODS: Consecutive patients with chronic iron-deficient anaemia
      (IDA) with H. pylori infection and a negative standard work-up were prospectively
      evaluated. All of them had either iron refractoriness or iron dependency.
      Response to H. pylori eradication was assessed at 6 and 12 mo from follow-up. H.
      pylori infection was considered to be the cause of the anaemia when a complete
      anaemia resolution without iron supplements was observed after eradication.
      RESULTS: H. pylori was eradicated in 88 of the 89 patients. In the non-eradicated
      patient the four eradicating regimens failed. There were violations of protocol
      in 4 patients, for whom it was not possible to ascertain the cause of the
      anaemia. Thus, 84 H. pylori eradicated patients (10 men; 74 women) were available
      to assess the effect of eradication on IDA. H. pylori infection was considered to
      be the aetiology of IDA in 32 patients (38.1%; 95%CI: 28.4%-48.8%). This was more
      frequent in men/postmenopausal women than in premenopausal women (75% vs 23.3%; P
      < 0.0001) with an OR of 9.8 (95%CI: 3.3-29.6). In these patients, anaemia
      resolution occurred in the first follow-up visit at 6 mo, and no anaemia or iron
      deficiency relapse was observed after a mean follow-up of 21 +/- 2 mo.
      CONCLUSION: Gastric H. pylori infection is a frequent cause of iron-refractory or
      iron-dependent anaemia of previously unknown origin in adult patients.

PMID- 23864778
TI  - Reversal of multidrug resistance in gastric cancer cells by CDX2 downregulation.
AB  - AIM: To explore the role of CDX2 in the multi-drug resistance (MDR) process of
      gastric cancer in vitro and in vivo. METHODS: A cisplatin-resistant gastric
      cancer cell line with stable downregulation of CDX2 was established. mRNA and
      protein expression levels of CDX2, survivin, cyclin D1, and c-Myc were detected
      by western blotting and semi-quantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR). The influence of downregulation of CDX2 on MDR was assessed by
      measuring IC50 of SGC7901/DDP cells to cisplatin, doxorubicin, and 5
      fluorouracil, rate of doxorubicin efflux, apoptosis, and cell cycle progression
      detected by flow cytometry. In addition, we determined the in vivo effects of
      CDX2 small interfering RNA (siRNA) on tumor size, and apoptotic cells in tumor
      tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end labeling and hematoxylin and eosin staining. RESULTS: CDX2 siRNA led to
      downregulation of endogenous CDX2 mRNA (0.31 +/- 0.05 vs 1.10 +/- 0.51, 0.31 +/-
      0.05 vs 1.05 +/- 0.21, P = 0.003) and protein (0.12 +/- 0.08 vs 0.51 +/- 0.07,
      0.12 +/- 0.08 vs 0.55 +/- 0.16, P = 2.57 * 10(-4)) expression. It significantly
      promoted the sensitivity of SGC7901/DDP cells to cisplatin (0.12 +/- 0.05 vs 0.33
      +/- 0.08, 0.12 +/- 0.05 vs 0.39 +/- 0.15, P = 0.001), doxorubicin (0.52 +/- 0.13
      vs 4.11 +/- 1.25, 0.52 +/- 0.13 vs 4.05 +/- 1.44, P = 2.81 * 10(-4)), and 5
      fluorouracil (0.82 +/- 0.13 vs 2.81 +/- 0.51, 0.82 +/- 0.13 vs 3.28 +/- 1.03, P =
      1.71 * 10(-4)). Flow cytometry confirmed that the percentage of apoptotic cells
      increased after CDX2 downregulation (32.15% +/- 2.15% vs 17.63% +/- 3.16%, 32.15%
      +/- 2.15% vs 19.3% +/- 2.25%, P = 1.73 * 10(-6)). This notion was further
      supported by the observation that downregulation of CDX2 blocked entry into the S
      phase of the cell cycle (31.53% +/- 3.78% vs 65.05% +/- 7.25%, 31.53% +/- 3.78%
      vs 62.27% +/- 5.02%, P = 7.55 * 10(-7)). Furthermore, downregulation of CDX2
      significantly increased intracellular accumulation of doxorubicin (0.21 +/- 0.06
      vs 0.41 +/- 0.11, 0.21 +/- 0.06 vs 0.40 +/- 0.08, P = 0.003). In molecular
      studies, semiquantitative RT-PCR and western blotting revealed that CDX2
      downregulation could inhibit expression of c-Myc, survivin and cyclin D1.
      CONCLUSION: CDX2 may be involved in regulating multiple signaling pathways in
      reversing MDR, suggesting that CDX2 may represent a novel target for gastric
      cancer therapy.

PMID- 23864780
TI  - Single endoscopist-performed percutaneous endoscopic gastrostomy tube placement.
AB  - AIM: To investigate whether single endoscopist-performed percutaneous endoscopic
      gastrostomy (PEG) is safe and to compare the complications of PEG with those
      reported in the literature. METHODS: Patients who underwent PEG placement between
      June 2001 and August 2011 at the Baskent University Alanya Teaching and Research
      Center were evaluated retrospectively. Patients whose PEG was placed for the
      first time by a single endoscopist were enrolled in the study. PEG was performed
      using the pull method. All of the patients were evaluated for their indications
      for PEG, major and minor complications resulting from PEG, nutritional status, C
      reactive protein (CRP) levels and the use of antibiotic treatment or antibiotic
      prophylaxis prior to PEG. Comorbidities, rates, time and reasons for mortality
      were also evaluated. The reasons for PEG removal and PEG duration were also
      investigated. RESULTS: Sixty-two patients underwent the PEG procedure for the
      first time during this study. Eight patients who underwent PEG placement by 2
      endoscopists were not enrolled in the study. A total of 54 patients were
      investigated. The patients' mean age was 69.9 years. The most common indication
      for PEG was cerebral infarct, which occurred in approximately two-thirds of the
      patients. The mean albumin level was 3.04 +/- 0.7 g/dL, and 76.2% of the
      patients' albumin levels were below the normal values. The mean CRP level was
      high in 90.6% of patients prior to the procedure. Approximately two-thirds of the
      patients received antibiotics for either prophylaxis or treatment for infections
      prior to the PEG procedure. Mortality was not related to the procedure in any of
      the patients. Buried bumper syndrome was the only major complication, and it
      occurred in the third year. In such case, the PEG was removed and a new PEG tube
      was placed via surgery. Eight patients (15.1%) experienced minor complications, 6
      (11.1%) of which were wound infections. All wound infections except one recovered
      with antibiotic treatment. Two patients had bleeding from the PEG site, one was
      resolved with primary suturing and the other with fresh frozen plasma
      transfusion. CONCLUSION: The incidence of major and minor complications is in
      keeping with literature. This finding may be noteworthy, especially in developing
      countries.

PMID- 23864781
TI  - Comparison of double pants with single pants on satisfaction with colonoscopy.
AB  - AIM: To increase satisfaction and diminish anxiety and shame during colonoscopy,
      we developed novel double pants (NDP) which consist of doubled fabrics with an
      inner hole. The aim of study was to compare satisfaction, anxiety and shame
      between NDP and conventional single pants (CSP). METHODS: Total 160 consecutive
      examinees were randomly divided into NDP and CSP group. Before colonoscopy,
      questionnaires identifying state and trait anxiety were completed. After
      colonoscopy, questionnaires for overall satisfaction (Group Health Association of
      America 9) and pants-specific satisfaction (5-20), state anxiety (20-80), and
      shame (6-24) were interviewed. RESULTS: Pants-specific satisfaction scores
      regarding willingness to repeat colonoscopy using same pants (3.3 +/- 0.8 vs 2.1
      +/- 0.9, P < 0.001) and recommendation of same pants to other people (3.3 +/- 0.7
      vs 2.0 +/- 1.0, P < 0.001) were significantly higher in NDP than CSP groups.
      State anxiety (33.0 +/- 7.0 vs 35.4 +/- 6.9, P = 0.028) and shame (6.6 +/- 1.5 vs
      8.1 +/- 3.2, P = 0.001) after colonoscopy was lower in NDP group compared with
      CSP group. CONCLUSION: The NDP contribute to increase satisfaction and decrease
      anxiety and shame after colonoscopy.

PMID- 23864782
TI  - Cap polyposis: a rare cause of rectal bleeding in children.
AB  - AIM: To evaluate the clinicopathological features and treatment outcomes of cap
      polyposis in the pediatric population. METHODS: All pediatric patients with
      histologically proven diagnosis of cap polyposis were identified from our
      endoscopy and histology database over a 12 year period from 2000-2012 at our
      tertiary pediatric center, KK Women's and Children's Hospital in Singapore. The
      case records of these patients were retrospectively reviewed. The demographics,
      clinical course, laboratory results, endoscopic and histopathological features,
      treatments, and outcomes were analyzed. The study protocol was approved by the
      hospital institutional review board. The histological slides were reviewed by a
      pediatric histopathologist to confirm the diagnosis of cap polyposis. RESULTS:
      Eleven patients were diagnosed with cap polyposis. The median patient age was 13
      years (range 5-17 years); the sample included 7 males and 4 females. All of the
      patients presented with bloody stools. Seven patients (63%) had constipation,
      while 4 patients (36%) had diarrhea. All of the patients underwent colonoscopy
      and polypectomies (excluding 1 patient who refused polypectomy). The macroscopic
      findings were of polypoid lesions covered by fibrinopurulent exudates with normal
      intervening mucosa. The rectum was the most common involvement site (n = 9, 82%),
      followed by the rectosigmoid colon (n = 3, 18%). Five (45%) patients had fewer
      than 5 polyps, and 6 patients (65%) had multiple polyps. Histological examination
      of these polyps showed surface ulcerations with a cap of fibrin inflammatory
      exudate. Four (80%) patients with fewer than 5 polyps had complete resolution of
      symptoms following the polypectomy. One patient who did not consent to the
      polypectomy had resolution of symptoms after being treated with sulphasalazine.
      All 6 patients with multiple polyps experienced recurrence of bloody stools on
      follow-up (mean = 28 mo). CONCLUSION: Cap polyposis is a rare and under
      recognised cause of rectal bleeding in children. Our study has characterized the
      disease phenotype and treatment outcomes in a pediatric cohort.

PMID- 23864783
TI  - Transcatheter arterial chemoembolization followed by immediate radiofrequency
      ablation for large solitary hepatocellular carcinomas.
AB  - AIM: To assess the technical safety and efficacy of transcatheter arterial
      chemoembolization (TACE) combined with immediate radiofrequency ablation (RFA)
      for large hepatocellular carcinomas (HCC) (maximum diameter >= 5 cm). METHODS:
      Individual lesions in 18 patients with HCCs (mean maximum diameter: 7.5 cm;
      range: 5.1-15.5 cm) were treated by TACE combined with percutaneous RFA between
      January 2010 and June 2012. All of the patients had previously undergone one to
      four cycles of TACE treatment. Regular imaging and laboratory tests were
      performed to evaluate the rate of technical success, technique-related
      complications, local-regional tumor responses, recurrence-free survival time and
      survival rate after treatment. RESULTS: Technical success was achieved for all 18
      visible HCCs. Complete response (CR) was observed in 17 cases, and partial
      response was observed in 1 case 1 mo after intervention. The CR rate was 94.4%.
      Local tumors were mainly characterized by coagulative necrosis. During follow-up
      (2-29 mo), the mean recurrence-free survival time was 16.8 +/- 4.0 mo in 17 cases
      of CR. The estimated overall survival rate at 6, 12, and 18 mo was 100%. No major
      complications were observed. Levels of alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) in the blood of 17 patients transiently
      increased on the third day after treatment (ALT 200.4 +/- 63.4 U/L vs 24.7 +/-
      9.3 U/L, P < 0.05; AST 228.1 +/- 25.4 U/L vs 32.7 +/- 6.8 U/L, P < 0.05). Severe
      pain occurred in three patients, which was controlled with morphine and fentanyl.
      CONCLUSION: TACE combined with immediate RFA is a safe and effective treatment
      for large solitary HCCs. Severe pain is a major side effect, but can be
      controlled by morphine.

PMID- 23864784
TI  - Metabonomic studies of pancreatic cancer response to radiotherapy in a mouse
      xenograft model using magnetic resonance spectroscopy and principal components
      analysis.
AB  - AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before
      and after radiotherapy by high-resolution magic angle spinning proton magnetic
      resonance spectroscopy (HRMAS (1)H NMR) combined with principal components
      analysis (PCA) and evaluate the radiotherapeutic effect. METHODS: The nude mouse
      xenograft model of human pancreatic cancer was established by injecting human
      pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors
      volume reached 800 mm(3), the mice received various radiation doses. Two weeks
      later, tumor tissue sections were prepared for running the NMR measurements. (1)H
      NMR and PCA were used to determine the changes in the metabolic profiles of tumor
      tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic
      tumor tissues, and radiation- treated pancreatic tumor tissues were compared.
      RESULTS: Compared with (1)H NMR spectra of the normal nude mouse pancreas, the
      levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and
      glutamic acid of the pancreatic cancer group were increased, whereas an opposite
      trend for phosphocholine, glycerophosphocholine, and betaine was observed. The
      ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed
      noticeable decrease in the pancreatic cancer group. After further evaluation of
      the tissue metabolic profile after treatment with three different radiation
      doses, no significant change in metabolites was observed in the (1)H NMR spectra,
      while the inhibition of tumor growth was in proportion to the radiation doses.
      However, PCA results showed that the levels of choline and betaine were decreased
      with the increased radiation dose, and conversely, the level of acetic acid was
      dramatically increased. CONCLUSION: The combined methods were demonstrated to
      have the potential for allowing early diagnosis and assessment of pancreatic
      cancer response to radiotherapy.

PMID- 23864785
TI  - Laparoendoscopic single-site cholecystectomy vs three-port laparoscopic
      cholecystectomy: a large-scale retrospective study.
AB  - AIM: To perform a large-scale retrospective comparison of laparoendoscopic single
      site cholecystectomy (LESSC) and three-port laparoscopic cholecystectomy (TPLC)
      in a single institution. METHODS: Data were collected from 366 patients
      undergoing LESSC between January 2005 and July 2008 and were compared with the
      data from 355 patients undergoing TPLC between August 2008 and November 2011 in
      our department. Patients with body mass index greater than 35 kg/m(2), a history
      of major upper abdominal surgery, signs of acute cholecystitis, such as fever,
      right upper quadrant tenderness with or without Murphy's sign, elevated white
      blood cell count, imaging findings suggestive of pericholecystic fluid,
      gallbladder wall thickening > 4 mm, and gallstones > 3 cm, were excluded to avoid
      bias. RESULTS: Altogether, 298 LESSC and 315 TPLC patients met the inclusion
      criteria. The groups were well matched with regard to demographic data. There
      were no significant differences in terms of postoperative complications
      (contusion: 19 vs 25 and hematoma at incision: 11 vs 19), hospital stay (mean +/-
      SD, 1.4 +/- 0.2 d vs 1.4 +/- 0.7 d) and visual analogue pain score (mean +/- SD,
      8 h after surgery: 2.3 +/- 1.4 vs 2.3 +/- 1.3 and at day 1: 1.2 +/- 0.4 vs 1.3 +/
      1.2) between the LESSC and TPLC patients. Four patients required the addition of
      extra ports and 2 patients were converted to open surgery in the LESSC group,
      which was not significantly different when compared with TPLC patients converted
      to laparotomy (2 vs 2). LESSC resulted in a longer operating time (mean +/- SD,
      54.8 +/- 11.0 min vs 33.5 +/- 9.0 min), a higher incidence of intraoperative
      gallbladder perforation (56 vs 6) and higher operating cost (mean +/- SD, 1933.7
      +/- 64.4 USD vs 1874.7 +/- 46.2 USD) than TPLC. No significant differences in
      operating time (mean +/- SD, 34.3 +/- 6.0 min vs 32.7 +/- 8.7 min) and total cost
      (mean +/- SD, 1881.3 +/- 32.8 USD vs 1876.2 +/- 33.4 USD) were found when the
      last 100 cases in the two groups were compared. A correlation was observed
      between reduced operating time of LESSC and increased experience (Spearman rank
      correlation coefficient, -0.28). More patients in the LESSC group expressed
      satisfaction with the cosmetic result (98% vs 85%). CONCLUSION: LESSC is a safe
      and feasible procedure in selected patients with benign gallbladder diseases,
      with the significant advantage of cosmesis.

PMID- 23864786
TI  - Effect of amitriptyline on gastrointestinal function and brain-gut peptides: a
      double-blind trial.
AB  - AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal
      function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was
      a double-blind, randomised, placebo-controlled, two-period cross-over trial.
      Twenty-eight healthy volunteers were randomised and administered 1-wk treatments
      of AMT (12.5 mg tid) or placebo. Before and during the final two days of
      treatment, gastric emptying, proximal gastric accommodation and visceral
      sensitivity were measured by drinking-ultrasonography test; the orocecal transit
      time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was
      collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were
      measured by enzyme-linked immunosorbent assay kits. RESULTS: AMT slowed the OCTT
      (109.2 +/- 29.68 min vs 96.61 +/- 23.9 min, P = 0.004) but did not affect liquid
      gastric emptying and had no effect on proximal gastric accommodation. AMT
      resulted in decreases in the visual analogue scale (VAS) for difficulty in
      drinking 600 and 800 mL of water (3.57 +/- 0.94 vs 2.98 +/- 0.85, 5.57 +/- 0.82
      vs 4.57 +/- 0.98, P < 0.01 for both), although it had no significant effect on
      the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly
      increased the plasma ghrelin level (442.87 +/- 176.79 pg/mL vs 526.87 +/- 158.44
      pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 +/- 131.46 pg/mL vs 965.64
      +/- 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level.
      CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and
      increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low
      dose AMT for functional gastrointestinal disorders.

PMID- 23864787
TI  - Magnified and enhanced computed virtual chromoendoscopy in gastric neoplasia: a
      feasibility study.
AB  - AIM: To evaluate the feasibility of a new computed virtual chromoendoscopy (CVC)
      device (M i-scan) in the diagnosis of gastric neoplasia. METHODS: Patients with
      superficial lesions no larger than 1.0 cm found during high definition endoscopy
      were included. Those with advanced or obviously protruded or depressed lesions,
      lesions larger than 1.0 cm and/or lesions which were not amenable to observation
      by zoom function were excluded. The endoscopist was required to give the real
      time descriptions of surface pit patterns of the lesions, based on surface
      pattern classification of enhanced magnification endoscopy. According to previous
      reports, types I-III represent non-neoplastic lesions, and types IV-V represent
      neoplastic lesions. Diagnosis with M i-scan and biopsy was performed before
      histopathological diagnosis. Magnified images of gastric lesions with and without
      enhancement were collected for further analysis. The diagnostic yield of real
      time M i-scan and effects on magnification image quality by tone enhancement
      (TE), surface enhancement (SE) and color enhancement (CE) were calculated. The
      selected images were sent to another endoscopist. The endoscopist rated the image
      quality of each lesion at 3 levels. Ratings of image quality were based on
      visualization of pit pattern, vessel and demarcation line. RESULTS: One hundred
      and eighty-three patients were recruited. Five patients were excluded for
      advanced gastric lesions, 1 patient was excluded for poor preparation and 2
      patients were excluded for superficial lesions larger than 1.0 cm; 132 patients
      were excluded for no lesions found by high definition endoscopy. In the end, 43
      patients with 43 lesions were included. Histopathology revealed 10 inflammation,
      14 atrophy, 10 metaplasia, 1 low grade dysplasia (LGD), 5 high grade dysplasia
      (HGD) and 3 cancers. For 7 lesions classified into type I, histopathology
      revealed 6 atrophy and 1 metaplasia; for 10 lesions classified into type II,
      histopathology revealed 2 inflammation, 7 atrophy and 1 metaplasia; for 10
      lesions classified into type III, histopathology revealed 1 inflammation, 8
      metaplasia and 1 LGD; for 9 lesions classified into type IV, histopathology
      revealed 4 inflammation, 1 atrophy and 4 HGD; for 7 lesions classified into type
      V, histopathology revealed 3 inflammation, 1 HGD and 3 cancers. A total of 172
      still images, including 43 images by white light (MWL) and 129 images by M i-scan
      (43 with TE, 43 with SE and 43 with CE), were selected and sent to the
      endoscopist who did the analysis. General image quality of M i-scan with TE and
      SE was significantly better than that of MWL (TE, 4.55 +/- 1.07; SE, 4.30 +/-
      1.02; MWL, 3.25 +/- 0.99; P < 0.001). Visualization of pit pattern was
      significantly improved by M i-scan with SE (1.93 +/- 0.25 vs 1.50 +/- 0.50, P <
      0.001). Microvessel visualization was significantly improved by M i-scan with TE
      (1.23 +/- 0.78 vs 0.76 +/- 0.73, P < 0.001). Demarcation line visualization was
      improved by M i-scan with both TE and SE (TE, 1.75 +/- 0.52; SE, 1.56 +/- 0.59;
      MWL, 0.98 +/- 0.44; P < 0.001). M i-scan with CE did not show any significant
      improvements of image quality in general or in the 3 key parameters. Although M i
      scan with TE and SE slightly increased the diagnostic yield of MWL, there was no
      significant difference (P > 0.1). CONCLUSION: Although digital enhancement
      improves the image quality of magnification endoscopy, its value in improving the
      diagnostic yield seems to be limited.

PMID- 23864788
TI  - Effects of propranolol or propranolol plus isosorbide-5-mononitrate on variceal
      pressure in schistosomiasis.
AB  - AIM: To compare the effects of propranolol (PR) to that of PR plus isosorbide-5
      mononitrate (ISMN) on variceal pressure in patients with schistosomiasis.
      METHODS: Forty-eight patients with schistosomiasis who had no previous variceal
      bleeding were treated with PR alone or PR plus ISMN. Seven patients refused
      variceal pressure manometry (3 receiving PR and 4 receiving PR plus ISMN). One
      patient withdrew from the trial due to headache after taking ISMN. At the time of
      termination, twenty patients were randomly assigned to treatment with PR plus
      ISMN or PR alone. The dose of PR was adjusted until the resting heart rate had
      been reduced by 25% or was less than 55 bpm. In the PR plus ISMN group, after PR
      was titrated to the same target, the dose of ISMN was increased up to 20 mg
      orally twice a day. Variceal pressure was measured using a noninvasive endoscopic
      balloon technique at the end of the 6-mo treatment period. RESULTS: In 40
      patients (20 in the PR group and 20 in the PR plus ISMN group), variceal pressure
      was measured before treatment and at the end of the 6-mo treatment period. PR or
      PR plus ISMN treatment caused a significant reduction in variceal pressure (PR
      group: from 24.15 +/- 6.05 mmHg to 22.68 +/- 5.70 mmHg, P = 0.001; PR plus ISMN
      group: from 25.69 +/- 5.26 mmHg to 20.48 +/- 5.43 mmHg; P < 0.001). The
      percentage decrease in variceal pressure was significant after PR plus ISMN
      compared with that after PR alone (15.93% +/- 8.37% vs 6.05% +/- 3.67%, P =
      0.01). One patient in the PR plus ISMN group and two patients in the PR group had
      variceal bleeding during follow-up. There were no significant differences between
      the two groups regarding the incidence of variceal bleeding. In the PR plus ISMN
      group, three patients had headache and hypotension. The headache was mild and
      transient and promptly disappeared after continuation of the relevant drug in two
      patients. Only one patient withdrew from the trial due to severe and lasting
      headache after taking ISMN. No side effects occurred in the PR group. CONCLUSION:
      PR plus ISMN therapy may be an alternative treatment for patients with
      schistosomiasis who have a high risk of bleeding.

PMID- 23864789
TI  - Hepatitis B or C viral infection and risk of pancreatic cancer: a meta-analysis
      of observational studies.
AB  - AIM: To investigate if there is an association between hepatitis B virus (HBV) or
      hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All
      relevant studies published before 11 October, 2012 were identified by a
      systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library
      databases and with cross-referencing. The observational studies that reported RR
      or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic
      cancer were included. A random-effects model was used to summarize meta-analytic
      estimates. The Newcastle-Ottawa quality assessment scale was applied to assess
      the quality of the methodology in the included studies. RESULTS: A total of 8
      eligible studies were selected for meta-analysis. Overall, chronic hepatitis B
      and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive)
      had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI:
      1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56).
      Past exposure to HBV (possible occult HBV infection) had an increased OR of
      pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those
      patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis
      B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22).
      However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs
      positive) had no association with pancreatic cancer development, with OR 0.98
      (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen
      positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer
      among anti-HBs positive patients was significantly lower than among anti-HBs
      negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also
      resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50).
      Significant between-study heterogeneity was observed. Evidence of publication
      bias for HBV/HCV infection-pancreatic cancer association was not found.
      CONCLUSION: Chronic HBV and HCV infection increases pancreatic cancer risk. Our
      findings underscore the need for more studies to confirm this potential
      relationship.

PMID- 23864790
TI  - Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric
      cancer.
AB  - AIM: To investigate the association between babA2 gene and peptic ulcer disease
      (PUD) and gastric cancer (GC) in Helicobacter pylori-infected populations.
      METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD
      and GC) using a meta-analysis. A literature search was performed using the PubMed
      and Web of Science databases for relevant case-control studies that met the
      defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the
      association between babA2 genotype and clinical outcomes. A fixed-effect or
      random-effect model was performed depending on the absence or presence of
      significant heterogeneity. RESULTS: A total of 25 articles with 38 studies met
      the inclusion criteria and were finally included in this meta-analysis. The
      results showed that the babA2 genotype was significantly associated with an
      increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially
      in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006).
      Moreover, a significant association between babA2 gene and PUD and duodenal ulcer
      (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P <
      0.001, respectively) was observed in western countries but not in Asian
      countries. CONCLUSION: We demonstrated that the presence of babA2 may be
      associated with increased risks for PUD, especially duodenal ulcer, in western
      countries.

PMID- 23864791
TI  - Microscopic colitis: is it a spectrum of inflammatory bowel disease?
AB  - Lymphocytic and collagenous colitis are forms of microscopic colitis which
      typically presents in elderly patients as chronic watery diarrhea. The
      association between microscopic colitis and inflammatory bowel disease is weak
      and unclear. Lymphocytic colitis progressing to ulcerative colitis has been
      previously reported; however there is limited data on ulcerative colitis evolving
      into microscopic (lymphocytic or collagenous) colitis. We report a series of six
      patients with documented ulcerative colitis who subsequently were diagnosed with
      collagenous colitis or lymphocytic colitis suggesting microscopic colitis could
      be a part of the spectrum of inflammatory bowel disease. The median duration of
      ulcerative colitis prior to being diagnosed with microscopic colitis was 15
      years. We noted complete histological and/or symptomatic remission in three out
      of six cases while the other three patients reverted back into ulcerative colitis
      suggesting lymphocytic or collagenous colitis could present as a continuum of
      ulcerative colitis. The exact molecular mechanism of this histological
      transformation or the prognostic implications is still unclear. Till then it
      might be prudent to follow up these patients to assess for the relapse of
      inflammatory bowel disease as well as for dysplasia surveillance. 

PMID- 23864792
TI  - Alveolar echinococcosis-spreading disease challenging clinicians: a case report
      and literature review.
AB  - Human alveolar echinococcosis (AE) is a potentially deadly disease; recent
      studies have shown that the endemic area of Echinococcus multilocularis, its
      causative agent, is larger than previously known. This disease has low prevalence
      and remains underreported in Europe. Emerging clinical data show that diagnostic
      difficulties are still common. We report on a 76-year old patient suffering from
      AE lesions restricted to the left lobe of the liver who underwent a curative
      extended left hemihepatectomy. Prior to the resection a liver biopsy under the
      suspicion of an atypical malignancy was performed. After the intervention he
      developed a pseudoaneurysm of the hepatic artery that was successfully coiled.
      Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a
      growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a
      gross tumour composed of multiple large vesicles with several centimeters in
      diameter. In addition, there were neither extensive adhesions nor infiltrations
      of the neighboring pancreas and diaphragm as was expected from previous imaging
      results. The unexpected diagnosis of AE was confirmed by definite histopathology,
      specific polymerase chain reaction and serology results. This is a rare case of
      unusual macroscopic presentation of AE that posed immense diagnostic challenges
      and had an eventful course. To our knowledge this is the first case of an
      autochthonous infection in this particular geographic area of Germany, the
      federal state of Saxony. This report may provide new hints for an expanding area
      of risk for AE and emphasizes the risk of complications in the scope of
      diagnostic procedures and the limitations of modern radiological imaging. 

PMID- 23864793
TI  - A white opaque substance-positive gastric hyperplastic polyp with dysplasia.
AB  - The endoscopic findings of gastric hyperplastic polyps (HPs) with dysplasia have
      not been well-defined, and the clinical significance of these lesions, including
      their malignant potential, is unclear. In this report, we describe a case of a
      white opaque substance (WOS)-positive gastric HP with dysplasia. A 76-year-old
      woman was referred to our hospital for endoscopic resection of a gastric HP.
      Upper endoscopy revealed a 25-mm whitish and reddish polypoid lesion on the
      greater curvature in the lower third of the stomach. The whitish part was
      diagnosed as a WOS using conventional and magnifying endoscopy with narrow band
      imaging. An examination of the biopsy specimen indicated that the lesion was a
      typical gastric HP. However, because of its color and the presence of a WOS, we
      suspected that this lesion was an atypical gastric HP. Therefore, we performed a
      polypectomy. Histopathologically, diffuse low- to high-grade dysplasia was found
      on the surface of the polyp. We performed immunohistochemical staining using a
      monoclonal antibody specific for adipophilin as a marker of lipid droplets (LDs).
      LDs were detected in approximately all of the neoplastic cells, especially in the
      surface epithelium of the intervening apical parts and were located in the
      subnuclear cytoplasm of the neoplastic cells. According to endoscopic and
      histopathological findings, the WOS-positive epithelium indicated dysplasia of
      the gastrointestinal phenotype, which could absorb lipids. The presence of a WOS
      in a gastric HP may be considered an endoscopic finding that is predictive of the
      neoplastic transformation of a gastric HP. We suggest that a WOS-positive gastric
      HP should be resected endoscopically to investigate its neoplastic
      transformation.

PMID- 23864794
TI  - Unexpected endoscopic full-thickness resection of a duodenal neuroendocrine
      tumor.
AB  - A 57-year-old man underwent endoscopy for investigation of a duodenal polyp.
      Endoscopy revealed a hemispheric submucosal tumor, about 5 mm in diameter, in the
      anterior wall of the duodenal bulb. Endoscopic biopsy disclosed a neuroendocrine
      tumor histologically, therefore endoscopic mucosal resection was conducted. The
      tumor was effectively and evenly elevated after injection of a mixture of 0.2%
      hyaluronic acid and glycerol at a ratio of 1:1 into the submucosal layer. A small
      amount of indigo-carmine dye was also added for coloration of injection fluid.
      The lesion was completely resected en bloc with a snare after submucosal fluid
      injection. Immediately, muscle-fiber-like tissues were identified in the marginal
      area of the resected defect above the blue-colored layer, which suggested
      perforation. The defect was completely closed with a total of 9 endoclips, and no
      symptoms associated with peritonitis appeared thereafter. Histologically, the
      horizontal and vertical margins of the resected specimen were free of tumor and
      muscularis propria was also seen in the resected specimen. Generally, endoscopic
      mucosal resection is considered to be theoretically successful if the mucosal
      defect is colored blue. The blue layer in this case, however, had been created by
      unplanned injection into the subserosal rather than the submucosal layer. 

PMID- 23864796
TI  - Vaccines against Coccidioides.
AB  - Vaccines against fungal diseases are gaining attention because of their growing
      impact on modern medicine. Development of these vaccines should incorporate
      immunological tools that integrate with or replace chemotherapy to minimize
      antibiotic use and consequent resistance. In this review, we evaluate the current
      developmental status of fungal vaccines against coccidioidomycosis. There is a
      need for a vaccine that sufficiently prevents disease, without eradicating the
      fungus, by neutralizing adhesions and enzymes or other low penetrance virulence
      traits. 

PMID- 23864797
TI  - Hepatitis B virus infection in South Korea: three decades after universal
      vaccination.

PMID- 23864795
TI  - Clinical applications of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are self-renewing, multipotent progenitor cells
      with multilineage potential to differentiate into cell types of mesodermal
      origin, such as adipocytes, osteocytes, and chondrocytes. In addition, MSCs can
      migrate to sites of inflammation and exert potent immunosuppressive and anti
      inflammatory effects through interactions between lymphocytes associated with
      both the innate and adaptive immune system. Along with these unique therapeutic
      properties, their ease of accessibility and expansion suggest that use of MSCs
      may be a useful therapeutic approach for various disorders. In the clinical
      setting, MSCs are being explored in trials of various conditions, including
      orthopedic injuries, graft versus host disease following bone marrow
      transplantation, cardiovascular diseases, autoimmune diseases, and liver
      diseases. Furthermore, genetic modification of MSCs to overexpress antitumor
      genes has provided prospects for clinical use as anticancer therapy. Here, we
      highlight the currently reported uses of MSCs in clinical trials and discuss
      their efficacy as well as their limitations. 

PMID- 23864798
TI  - Cyclophosphamide dose: how much is needed to win the war against paraquat
      poisoning?

PMID- 23864799
TI  - Recent trends in hepatitis B virus infection in the general Korean population.
AB  - BACKGROUND/AIMS: Hepatitis B virus (HBV) is the major cause of chronic liver
      disease in Korea, but viral prevalence has decreased because of hepatitis B
      vaccination programs. In this study, we investigated longitudinal changes in HBV
      in fection in the general Korean population. METHODS: HBV surface antigen
      (hepatitis B surface antigen, HBsAg) seropositivity was assessed from the Korea
      National Health and Nutrition Examination Survey (I to V). In total, 50,140
      subjects were tested for serum HBsAg positivity over a period of 12 years (1998
      to 2010). RESULTS: The prevalence of HBsAg seropositivity decreased over the
      study period. The rates of HBsAg carriers were 4.61% in 1998, 4.60% in 2001,
      3.69% in 2005, 3.01% in 2008, and 2.98% in 2010 (p < 0.0001). The reduction in
      HBV infection rates was more prominent in younger age groups. Among teenagers (10
      to 19 years), the percentage of HBsAg carriers decreased from 2.2% in 1998 to
      0.12% in 2010 (p < 0.0001). Among those aged 10 to 39 years, the percentage of
      HBV infection decreased from 4.72% in 1998 to 2.29% in 2010 (p < 0.0001).
      However, no decreasing trend in HBsAg positivity was observed among those aged 50
      or older (p > 0.05). Neither gender nor socioeconomic status were associated with
      the decreased prevalence of HBsAg carriers. CONCLUSIONS: HBV infection has
      decreased in the Korean population since the advent of vaccination programs.
      However, the decrease is limited to the younger population, and viral persistence
      remains in the middle-aged and older population.

PMID- 23864800
TI  - The dose of cyclophosphamide for treating paraquat-induced rat lung injury.
AB  - BACKGROUND/AIMS: Cyclophosphamide (CP) is a promising treatment for severe cases
      of paraquat (PQ) poisoning. We investigated the effective dose of CP for
      mitigating PQ-induced lung injury. METHODS: Adult male Sprague-Dawley rats were
      allocated into five groups: control, PQ (35 mg/kg, intraperitoneal injection),
      and PQ + CP (1.5, 15, or 30 mg/kg). The dimensions of lung lesions were
      determined using X-ray microtomography (micro-CT), and histological changes and
      cytokine levels were recorded. RESULTS: The micro-CT results showed that 15 mg/kg
      CP was more effective than 1.5 mg/kg CP for treating PQ-induced lung injury. At a
      dose of 1.5 mg/kg, CP alleviated the histological evidence of inflammation and
      altered superoxide dismutase activity. Using 15 mg/kg CP reduced the elevated
      catalase activity and serum transforming growth factor (TGF)-beta1 level.
      CONCLUSIONS: A CP dose of > 15 mg/kg is effective for reducing the severity of PQ
      induced lung injury as determined by histological and micro-CT tissue
      examination, possibly by modulating antioxidant enzyme and TGF-beta1 levels.

PMID- 23864801
TI  - Factors influencing hepatocellular carcinoma prognosis after hepatectomy: a
      single-center experience.
AB  - BACKGROUND/AIMS: Recurrence after hepatic resection is one of the most important
      factors impacting the prognosis and survival of patients with hepatocellular
      carcinoma (HCC). We identified prognostic factors affecting overall survival (OS)
      and disease-free survival (DFS) in patients with HCC after hepatic resection.
      METHODS: This study was of a retrospective cohort design, and 126 patients who
      underwent hepatic resection for HCC at Gachon University Gil Medical Center
      between January 2005 and December 2010 were enrolled. Various clinical,
      laboratory, and pathological data were evaluated to determine the prognostic
      factors affecting OS and DFS. RESULTS: Two- and 4-year OS and 2- and 4-year DFS
      were 78.1% and 65% and 51.1% and 26.6%, respectively. In a multivariate analysis,
      preoperative alpha-fetoprotein (> 400 ng/mL), tumor size (>= 5 cm), multiple
      tumors (two or more nodules), presence of portal vein invasion, modified Union
      for International Cancer Control (UICC) stage III/IV, and Barcelona Clinic Liver
      Cancer (BCLC) stage B/C were independent prognostic factors affecting a shorter
      OS. In the multivariate analysis, presence of microvascular invasion, modified
      UICC stage III/IV, and BCLC stage B/C were independent prognostic factors for a
      shorter DFS. CONCLUSIONS: The presence of vascular invasion was an independent
      poor prognostic factor for OS and DFS in patients with HCC after hepatic
      resection. Thus, close postoperative surveillance for early detection of
      recurrence and additional treatments are urgently needed in patients with
      vascular invasion after hepatic resection.

PMID- 23864802
TI  - Effects of D-002, a mixture of high molecular weight beeswax alcohols, on
      patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is intimately related
      to insulin resistance and ranges from a benign course to liver fibrosis and
      cirrhosis. NAFLD management mainly involves dietary modification and weight loss.
      Although no fully successful pharmacological intervention is available,
      alternative therapies to treat NAFLD have shown promising results. Experimental
      studies have shown that D-002, a mixture of beeswax alcohols with antioxidant
      effects, is hepatoprotective. The aim of this study was to investigate the
      efficacy and safety of D-002 in patients with NALFD. METHODS: Fifty patients with
      NAFLD were randomized to receive a placebo or D-002 (100 mg/day) for 24 weeks.
      The primary endpoint was a significant ultrasonography-detected reduction of
      liver fat infiltration versus a placebo. Secondary endpoints were decreases in
      the homeostatic model assessment (HOMA) index, insulin levels, serum liver
      enzymes, increases in plasma total antioxidant status (TAS) and improved clinical
      symptoms versus the placebo recipients. RESULTS: At randomization, all indicators
      were comparable in both groups. At study completion, seven (28.0%) D-002
      patients, but none of the placebo recipients, exhibited a normal liver echo
      pattern on ultrasonography (p < 0.01). Also, D-002 significantly reduced (p <
      0.01 vs. baseline and placebo) the HOMA index and insulin levels and increased
      the TAS, but did not affect other parameters. The proportion of D-002-patients
      (12/25, 48.0%) showing symptom improvement was higher (p < 0.001) than that of
      the placebo group (1/25, 4.0%). The treatment was safe and well tolerated. Three
      patients in each group withdrew from the study. CONCLUSIONS: D-002 (100 mg/day)
      improved ultrasonographic findings, indicators of insulin resistance, plasma TAS
      and clinical evolution on NAFLD patients. Further studies, however, are needed to
      confirm these results.

PMID- 23864803
TI  - The start of chemotherapy until the end of radiotherapy in patients with limited
      stage small cell lung cancer.
AB  - BACKGROUND/AIMS: Chemotherapy combined with radiation therapy is the standard
      treatment for limited stage small cell lung cancer (LS-SCLC). Although numerous
      studies indicate that the overall duration of chemoradiotherapy is the most
      relevant predictor of outcome, the optimal chemotherapy and radiation schedule
      for LS-SCLC remains controversial. Therefore we analyzed the time from the start
      of any treatment until the end of radiotherapy (SER) in patients with LS-SCLC.
      METHODS: We retrospectively analyzed 29 patients diagnosed histologically with LS
      SCLC and divided them into two groups: a short SER group (< 60 days) and a long
      SER (> 60 days) group. Patients were treated with irinotecan-based chemotherapy
      and thoracic radiotherapy. RESULTS: Sixteen patients were in the short SER group
      and 13 patients were in the long SER group. Short SER significantly prolonged
      survival rate (p = 0.03) compared with that of long SER. However, no significant
      differences in side effects were observed. CONCLUSIONS: Short SER should be
      considered to improve the outcome of concurrent chemoradiotherapy for LS-SCLC.

PMID- 23864804
TI  - Adipokines, insulin-like growth factor binding protein-3 levels, and insulin
      sensitivity in women with polycystic ovary syndrome.
AB  - BACKGROUND/AIMS: Many women with polycystic ovary syndrome (PCOS) exhibit insulin
      resistance. Adipose tissue plays an important role in insulin resistance, and
      adipokines including tumor necrosis factor (TNF)-alpha and adiponectin are
      altered in PCOS. Insulin-like growth factor binding protein-3 (IGFBP-3), alone or
      in conjunction with other adipokines, is also associated with insulin resistance.
      We evaluated the effects of TNF-alpha, adiponectin, and IGFBP-3 on insulin
      sensitivity and the relationships among these proteins in women with PCOS.
      METHODS: We recruited 40 women with PCOS and 40 age- and body mass index (BMI)
      matched regular cycling women (controls). The women were divided into obese (BMI
      >= 25 kg/m(2)) and nonobese (BMI < 25 kg/m(2)) groups. Anthropometric
      measurements were performed, and serum levels of TNF-alpha, adiponectin, and
      IGFBP-3 were determined. Insulin sensitivity was estimated using the metabolic
      clearance rate (MCR) of glucose calculated from the oral glucose tolerance test.
      RESULTS: Serum levels of TNF-alpha and IGFBP-3 did not differ between the PCOS
      and control groups, but adiponectin levels in the PCOS group were lower than
      those in control women in the nonobese group (p < 0.05). TNF-alpha, adiponectin,
      and IGFBP-3 levels were not correlated with each other in women with PCOS, but a
      significant positive correlation was observed between adiponectin levels and MCR
      (p < 0.05). Multiple regression analysis revealed that adiponectin levels were
      significantly associated with insulin sensitivity (p < 0.05) in women with PCOS.
      CONCLUSIONS: IGFBP-3 and TNF-alpha levels were not associated with insulin
      sensitivity, but adiponectin levels were related to insulin sensitivity in women
      with PCOS.

PMID- 23864805
TI  - Accelerated progression of arterial stiffness in dialysis patients compared with
      the general population.
AB  - BACKGROUND/AIMS: The aim of this study was to compare the progression of aortic
      stiffness in chronic hemodialysis patients (CHP) with that of general population
      patients (GPP) over a 36-month period and to evaluate the determinants of this
      progression. METHODS: The study group included 80 patients undergoing
      hemodialysis (aged 59.3 +/- 11.8 years; duration of dialysis 5.47 +/- 5.16
      years). The control group consisted of 60 patients (aged 57.5 +/- 10.9 years)
      with a glomerular filtration rate of > 60 mL/min/1.73 m(2). Pulse wave velocity
      (PWV) was determined from time diversity propagation of the common carotid artery
      and femoral artery by Doppler ultrasound. Clinical and biochemical parameters
      were determined in serum using standard laboratory procedures. RESULTS: The mean
      PWV values at baseline and 36 months were 11.18 +/- 2.29 and 11.82 +/- 2.34 m/sec
      in the CHP group, and 9.02 +/- 1.89 and 9.29 +/- 1.93 m/sec in the GPP group,
      respectively. The average PWV progressions were 63.95 +/- 18.373 cm/sec in CHP
      and 27.28 +/- 28.519 cm/sec in GPP. By multiple regression analysis, hemoglobin
      (standardized coefficient beta [betast] = -0.405, p = 0.004; betast = -0.364, p =
      0.011), albumin (betast = -0.349, p = 0.042; betast = -0.303, p = 0.034), CRP
      (betast = 0.458, p = 0.002; betast = 0.187, p = 0.008), and total cholesterol
      (betast = 0.236, p = 0.038; betast = 0.171, p = 0.078) were independently
      associated with PWV in the CHP and GPP groups, respectively. CONCLUSIONS:
      Accelerated arterial stiffness was more pronounced in the CHP group than in the
      GPP group. The independent determinants of this progression in both groups
      include traditional risk factors and blood levels of hemoglobin, albumin and CRP.
      Cholesterol and uremia-related factors are determinants only in CHP.

PMID- 23864806
TI  - Malakoplakia in a healthy young female patient.
AB  - Malakoplakia is a rare granulomatous disease that occurs commonly in the urinary
      tract and secondarily in the gastrointestinal tract. Most reported cases of
      malakoplakia are associated with immunosuppressive diseases or chronic prolonged
      illness. Here, we report a rare case of malakoplakia in a young healthy
      adolescent without any underlying disease. A 19-year-old female was referred to
      our hospital following the discovery of multiple rectal polyps with
      sigmoidoscopy. She had no specific past medical history but complained of
      recurrent abdominal pain and diarrhea for 3 months. A colonoscopy revealed
      diverse mucosal lesions including plaques, polyps, nodules, and mass-like
      lesions. Histological examination revealed a sheet of histiocytes with
      pathognomonic Michaelis-Gutmann bodies. We treated the patient with
      ciprofloxacin, the cholinergic agonist bethanechol, and a multivitamin for 6
      months. A follow-up colonoscopy revealed that her condition was resolved with
      this course of treatment. 

PMID- 23864807
TI  - Successful coronary stent retrieval from the ascending aorta using a gooseneck
      snare kit.
AB  - Coronary stent dislodgement is a rare complication of percutaneous coronary
      intervention. We report a case of stent dislodgement in the ascending thoracic
      aorta. The stent was mechanically distorted in the left circumflex artery (LCX)
      while being delivered to the proximal LCX lesion. The balloon catheter was
      withdrawn, but the stent with the guide wire was remained in the ascending
      thoracic aorta. The stent was unable to be retrieved into the guide catheter, as
      it was distorted. A goose neck snare was used successfully to catch the stent in
      the ascending thoracic aorta and retrieved the stent externally via the arterial
      sheath. 

PMID- 23864808
TI  - A case of fulminant community-acquired Acinetobacter baumannii pneumonia in
      Korea.
AB  - Acinetobacter baumannii (AB) is a common pathogen found in patients with hospital
      acquired pneumonia all over the world. Community-acquired AB pneumonia, however,
      is very rare and has seldom been reported in Asia-Pacific countries. Community
      acquired AB pneumonia has a fulminant course and is associated with a higher
      mortality than hospital-acquired AB pneumonia. In Korea, no case of fatal
      community-acquired AB pneumonia has been reported to date. Here, we describe the
      first fatal case of fulminant community-acquired AB pneumonia in Korea. 

PMID- 23864809
TI  - Takayasu arteritis associated with ulcerative colitis and optic neuritis: first
      case in Korea.
AB  - Takayasu arteritis (TA) is a chronic vasculitis that affects the aortic arch and
      its primary branches. Ulcerative colitis (UC) is an inflammatory bowel disease of
      unknown etiology. Patients diagnosed with both TA and UC have rarely been
      reported. The pathogenesis of TA and UC is uncertain, but cell-mediated
      mechanisms play an important role in both diseases, and a genetic factor is
      thought to have an effect on the coincidence of these two diseases. We herein
      report a 38-year-old female with TA who had a history of UC with optic neuritis.
      We believe that this is the first case of the coexistence of TA and UC in Korea. 

PMID- 23864810
TI  - Cytomegalovirus esophagitis presents as chest pain in a renal transplant
      recipient.

PMID- 23864811
TI  - Positron emission tomography detection of synchronous colon cancer in a patient
      with chronic lymphocytic leukemia.

PMID- 23864812
TI  - What caused hemolytic anemia and colicky abdominal pain? Lead!

PMID- 23864813
TI  - Sensitivities of seasonal and pandemic rapid antigen tests differentiated by the
      level of immunofluorescence for the detection of pandemic influenza A/H1N1 2009
      virus.

PMID- 23864814
TI  - A solitary necrotic nodule of the liver.

PMID- 23864815
TI  - Rheumatoid pannus compressing the medulla oblongata.

PMID- 23864817
TI  - Metastatic pattern, local relapse, and survival of patients with myxoid
      liposarcoma: a retrospective study of 45 patients.
AB  - Purpose. To assess the metastatic pattern of the histological subtype myxoid
      liposarcoma (MLS) with no or few round cells. Methods. Forty-five patients (F/M =
      27/18, mean age 49 (range 17-85) years) were diagnosed with MLS at two Danish
      sarcoma centres in the period 1995-2004. A retrospective review of patients'
      files combined with an extraction of survival data from the Danish Centralised
      Civil Register was performed. Results. Seven patients had distant metastases
      during the observation period. Two patients had metastases at the time of
      diagnosis, while metastases occurred within 2.5 years in four patients, and in
      one patient 11.9 years after primary diagnosis. All metastases occurred at
      extrapulmonary sites. The first local relapse occurred within 3 years after
      surgery in six patients, in one patient after 4.0 years, and in one patient 7.7
      years after surgery. The 5- and 10-year overall survival was 80% and 69%,
      respectively. Both the 5- and 10-year distant metastases-free survival was,
      respectively, 86%. The 5- and 10-year local relapse-free survival was,
      respectively, 83% and 80%. Conclusions. Patients with MLS had only extra
      pulmonary metastases, and no lung metastases were found. Most local relapses and
      distant metastases occurred within the first 2-3 years after surgery. 

PMID- 23864818
TI  - Strong field-induced frequency conversion of laser radiation in plasma plumes:
      recent achievements.
AB  - New findings in plasma harmonics studies using strong laser fields are reviewed.
      We discuss recent achievements in the growth of the efficiency of coherent
      extreme ultraviolet (XUV) radiation sources based on frequency conversion of the
      ultrashort pulses in the laser-produced plasmas, which allowed for the spectral
      and structural studies of matter through the high-order harmonic generation (HHG)
      spectroscopy. These studies showed that plasma HHG can open new opportunities in
      many unexpected areas of laser-matter interaction. Besides being considered as an
      alternative method for generation of coherent XUV radiation, it can be used as a
      powerful tool for various spectroscopic and analytical applications. 

PMID- 23864819
TI  - Population-based study of the association between urbanization and Kawasaki
      disease in Taiwan.
AB  - Background. It is unclear if the prevalence of Kawasaki disease (KD) correlates
      with the degree of urbanization. We hypothesized that the prevalence of KD is
      more pronounced in urban versus rural environments. Methods. The National Health
      Insurance (NHI) program was implemented in Taiwan in 1995 and covers most of the
      population (>99%). We used the NHI database to investigate the epidemiological
      features of KD. A total of 115 diagnosed patients with KD from 1997 to 2010 were
      included, together with 1,150 matched controls without KD. Chi-square analyses
      were performed to investigate the difference between modern city and rural
      environments. Results. Of the 1265 sampled subjects (claims data from 1,000,000
      random subjects), the mean age of the KD study group and control group was 2.08
      +/- 1.66 and 2.08 +/- 1.64 years, respectively. After matching for age, sex, and
      same index date, no statistically significant differences in urbanization level
      and geographical location of the patients' residence were observed. Conclusion.
      Urbanization did not appear to be an important effect modifier of Kawasaki
      disease in Taiwan. 

PMID- 23864820
TI  - Research on an infectious disease transmission by flocking birds.
AB  - The swarm intelligence is becoming a hot topic. The flocking of birds is a
      natural phenomenon, which is formed and organized without central or external
      controls for some benefits (e.g., reduction of energy consummation). However, the
      flocking also has some negative effects on the human, as the infectious disease
      H7N9 will easily be transmited from the denser flocking birds to the human.
      Zombie-city model has been proposed to help analyzing and modeling the flocking
      birds and the artificial society. This paper focuses on the H7N9 virus
      transmission in the flocking birds and from the flocking birds to the human. And
      some interesting results have been shown: (1) only some simple rules could result
      in an emergence such as the flocking; (2) the minimum distance between birds
      could affect H7N9 virus transmission in the flocking birds and even affect the
      virus transmissions from the flocking birds to the human. 

PMID- 23864821
TI  - 3D-Web-GIS RFID location sensing system for construction objects.
AB  - Construction site managers could benefit from being able to visualize on-site
      construction objects. Radio frequency identification (RFID) technology has been
      shown to improve the efficiency of construction object management. The objective
      of this study is to develop a 3D-Web-GIS RFID location sensing system for
      construction objects. An RFID 3D location sensing algorithm combining Simulated
      Annealing (SA) and a gradient descent method is proposed to determine target
      object location. In the algorithm, SA is used to stabilize the search process and
      the gradient descent method is used to reduce errors. The locations of the
      analyzed objects are visualized using the 3D-Web-GIS system. A real construction
      site is used to validate the applicability of the proposed method, with results
      indicating that the proposed approach can provide faster, more accurate, and more
      stable 3D positioning results than other location sensing algorithms. The
      proposed system allows construction managers to better understand worksite
      status, thus enhancing managerial efficiency. 

PMID- 23864822
TI  - Imaging tasks scheduling for high-altitude airship in emergency condition based
      on energy-aware strategy.
AB  - Aiming to the imaging tasks scheduling problem on high-altitude airship in
      emergency condition, the programming models are constructed by analyzing the main
      constraints, which take the maximum task benefit and the minimum energy
      consumption as two optimization objectives. Firstly, the hierarchy architecture
      is adopted to convert this scheduling problem into three subproblems, that is,
      the task ranking, value task detecting, and energy conservation optimization.
      Then, the algorithms are designed for the sub-problems, and the solving results
      are corresponding to feasible solution, efficient solution, and optimization
      solution of original problem, respectively. This paper makes detailed
      introduction to the energy-aware optimization strategy, which can rationally
      adjust airship's cruising speed based on the distribution of task's deadline, so
      as to decrease the total energy consumption caused by cruising activities.
      Finally, the application results and comparison analysis show that the proposed
      strategy and algorithm are effective and feasible. 

PMID- 23864823
TI  - Order batching in warehouses by minimizing total tardiness: a hybrid approach of
      weighted association rule mining and genetic algorithms.
AB  - One of the cost-intensive issues in managing warehouses is the order picking
      problem which deals with the retrieval of items from their storage locations in
      order to meet customer requests. Many solution approaches have been proposed in
      order to minimize traveling distance in the process of order picking. However, in
      practice, customer orders have to be completed by certain due dates in order to
      avoid tardiness which is neglected in most of the related scientific papers.
      Consequently, we proposed a novel solution approach in order to minimize
      tardiness which consists of four phases. First of all, weighted association rule
      mining has been used to calculate associations between orders with respect to
      their due date. Next, a batching model based on binary integer programming has
      been formulated to maximize the associations between orders within each batch.
      Subsequently, the order picking phase will come up which used a Genetic Algorithm
      integrated with the Traveling Salesman Problem in order to identify the most
      suitable travel path. Finally, the Genetic Algorithm has been applied for
      sequencing the constructed batches in order to minimize tardiness. Illustrative
      examples and comparisons are presented to demonstrate the proficiency and
      solution quality of the proposed approach. 

PMID- 23864824
TI  - Diurnal characteristics of ecosystem respiration of alpine meadow on the Qinghai
      Tibetan Plateau: implications for carbon budget estimation.
AB  - Accurately estimating daily mean ecosystem respiration rate (Re) is important for
      understanding how ecosystem carbon budgets will respond to climate change.
      Usually, daily mean Re is represented by measurement using static chamber on
      alpine meadow ecosystems from 9:00 to 11:00 h a.m. local time directly. In the
      present study, however, we found that the calculated daily mean Re from 9:00 to
      11:00 h a.m. local time was significantly higher than that from 0:00 to 23:30 h
      local time in an alpine meadow site, which might be caused by special climate
      condition on the Qinghai-Tibetan Plateau. Our results indicated that the
      calculated daily mean Re from 9:00 to 11:00 h a.m. local time cannot be used to
      represent daily mean Re directly. 

PMID- 23864825
TI  - Leaf epidermis of the rheophyte Dyckia brevifolia Baker (Bromeliaceae).
AB  - Some species of Dyckia Schult. f., including Dyckia brevifolia Baker, are
      rheophytes that live in the fast-moving water currents of streams and rivers
      which are subject to frequent flooding, but also period of low water. This study
      aimed to analyze the leaf epidermis of D. brevifolia in the context of epidermal
      adaptation to this aquatic plant's rheophytic habitat. The epidermis is
      uniseriate, and the cuticle is thickened. The inner periclinal and anticlinal
      walls of the epidermal cells are thickened and lignified. Stomata are tetracytic,
      located in the depressions in relation to the surrounding epidermal cells, and
      covered by peltate trichomes. While the epidermal characteristics of D.
      brevifolia are similar to those of Bromeliaceae species, this species has made
      particular adaptations of leaf epidermis in response to its rheophytic
      environment. 

PMID- 23864826
TI  - Amniotic fluid or its fatty acids produce actions similar to diazepam on lateral
      septal neurons firing rate.
AB  - Human amniotic fluid (AF) contains eight fatty acids (FATs), and both produce
      anxiolytic-like effects in adult rats and appetitive responses in human newborns.
      The medial amygdala and lateral septal nucleus function are related to social
      behavior, but the action of AF or its FATs in this circuit is known. We obtained
      267 single-unit extracellular recordings in Wistar rats treated with vehicle (1
      mL, s.c.; n = 12), human AF (1 mL, s.c.; n = 12), a FAT mixture (1 mL, s.c.; n =
      13), diazepam (1 mg/kg, i.p.; n = 11), and fluoxetine (1 mg/kg, p.o.; n = 12).
      Compared with the vehicle group, the spontaneous septal firing rate in the AF,
      FAT mixture, and diazepam groups was the lowest and in the fluoxetine group the
      highest. Cumulative peristimulus histograms indicated that the significant change
      in septal firing occurred only in the AF and FAT mixture groups and exclusively
      in those neurons that increased their firing rate during amygdala stimulation. We
      conclude that human AF and its FATs produce actions comparable to anxiolytic
      drugs and are able to modify the responsivity of a circuit involved in social
      behavior, suggesting facilitation of social recognition processes by maternal
      fetal fluids. 

PMID- 23864827
TI  - Nitrogen and potassium concentrations in the nutrients solution for melon plants
      growing in coconut fiber without drainage.
AB  - With the objective of evaluating the effects of N and K concentrations for melon
      plants, an experiment was carried out from July 1, 2011 to January 3, 2012 in
      Muzambinho city, Minas Gerais State, Brazil. The "Bonus no. 2" was cultivated at
      the spacing of 1.1 * 0.4. The experimental design was a randomized complete block
      with three replications in a 4 * 4 factorial scheme with four N concentrations
      (8, 12, 16, and 20 mmol L(-1)) and four K concentrations (4, 6, 8, and 10 mmol L(
      1)). The experimental plot constituted of eight plants. It was observed that the
      leaf levels of N and K, of N-NO3 and of K, and the electrical conductivity (CE)
      of the substrate increased with the increment of N and K in the nutrients'
      solution. Substratum pH, in general, was reduced with increments in N
      concentration and increased with increasing K concentrations in the nutrients'
      solution. Leaf area increased with increments in N concentration in the nutrients
      solution. Fertigation with solutions stronger in N (20 mmol L(-1)) and K (10 mmol
      L(-1)) resulted in higher masses for the first (968 g) and the second (951 g)
      fruits and crop yield (4,425 gm(-2)).

PMID- 23864828
TI  - Effects of using pozzolan and Portland cement in the treatment of dispersive
      clay.
AB  - Use of dispersive clay as construction material requires treatment such as by
      chemical addition. Treatments to dispersive clay using pozzolan and Portland
      cement, singly and simultaneously, were carried out in this study. When used
      alone, the optimum amount of pozzolan required to treat a fully dispersive clay
      sample was 5%, but the curing time to reduce dispersion potential, from 100% to
      30% or less, was 3 month long. On the other hand, also when used alone, a 3%
      cement content was capable of reducing dispersion potential to almost zero
      percent in only 7 days; and a 2% cement content was capable of achieving similar
      result in 14 days. However, treatment by cement alone is costly and could
      jeopardize the long term performance. Thus, a combined 5% pozzolan and 1.5%
      cement content was found capable of reducing dispersion potential from 100% to
      zero percent in 14 days. The results indicate that although simultaneous
      treatment with pozzolan and cement would extend the required curing time in
      comparison to treatment by cement alone of a higher content, the task could still
      be carried out in a reasonable period of curing time while avoiding the drawbacks
      of using either pozzolan or cement alone. 

PMID- 23864830
TI  - Predicting subcontractor performance using web-based Evolutionary Fuzzy Neural
      Networks.
AB  - Subcontractor performance directly affects project success. The use of
      inappropriate subcontractors may result in individual work delays, cost overruns,
      and quality defects throughout the project. This study develops web-based
      Evolutionary Fuzzy Neural Networks (EFNNs) to predict subcontractor performance.
      EFNNs are a fusion of Genetic Algorithms (GAs), Fuzzy Logic (FL), and Neural
      Networks (NNs). FL is primarily used to mimic high level of decision-making
      processes and deal with uncertainty in the construction industry. NNs are used to
      identify the association between previous performance and future status when
      predicting subcontractor performance. GAs are optimizing parameters required in
      FL and NNs. EFNNs encode FL and NNs using floating numbers to shorten the length
      of a string. A multi-cut-point crossover operator is used to explore the
      parameter and retain solution legality. Finally, the applicability of the
      proposed EFNNs is validated using real subcontractors. The EFNNs are evolved
      using 22 historical patterns and tested using 12 unseen cases. Application
      results show that the proposed EFNNs surpass FL and NNs in predicting
      subcontractor performance. The proposed approach improves prediction accuracy and
      reduces the effort required to predict subcontractor performance, providing field
      operators with web-based remote access to a reliable, scientific prediction
      mechanism. 

PMID- 23864829
TI  - Planktonic rotifers in a subtropical shallow lake: succession, relationship to
      environmental factors, and use as bioindicators.
AB  - Changes in the density and species composition of planktonic rotifers as well as
      their relationship to several environmental variables were studied at Dadian
      Lake, a shallow subtropical lake, which was completely dredged and reconstructed.
      Samples were taken monthly (2006-2009) at five stations. The total rotifer
      abundance exponentially declined and reached a relatively stable stage in 2009.
      Polyarthra dolichoptera and Trichocerca pusilla dominated the rotifer community
      in most seasons. TN, TP, and CODMn went down at the beginning of the monitoring
      period, rebounded in the second winter, and then decreased and reached a stable
      state in 2009. CCA showed that the most significant variations were caused by
      fluctuations in temperature, COD(Mn), SRP, and NO2-N. The rotifer community
      experienced a two-stage succession and the difference of species between the
      stages was exhibited during warm seasons. GAMs indicated that the selected
      factors were responsible for 64.8% of the total rotifer abundance variance and
      16.5~64.3% of the variances of individual species abundance. Most of the
      environmental parameters had effects on rotifer abundance that could only be
      described by complicated curves, characterised by unimodality and bimodality
      instead of linearity. Our study highlighted the temperature influence on rotifer
      species composition and total abundance in subtropical lakes.

PMID- 23864831
TI  - A new linearized Crank-Nicolson mixed element scheme for the extended Fisher
      Kolmogorov equation.
AB  - We present a new mixed finite element method for solving the extended Fisher
      Kolmogorov (EFK) equation. We first decompose the EFK equation as the two second
      order equations, then deal with a second-order equation employing finite element
      method, and handle the other second-order equation using a new mixed finite
      element method. In the new mixed finite element method, the gradient ?u belongs
      to the weaker (L2(Omega))2 space taking the place of the classical H(div; Omega)
      space. We prove some a priori bounds for the solution for semidiscrete scheme and
      derive a fully discrete mixed scheme based on a linearized Crank-Nicolson method.
      At the same time, we get the optimal a priori error estimates in L2 and H1-norm
      for both the scalar unknown u and the diffusion term w = -Deltau and a priori
      error estimates in (L2)2-norm for its gradient chi = ?u for both semi-discrete
      and fully discrete schemes.

PMID- 23864833
TI  - Study of Zn-Cu ferrite nanoparticles for LPG sensing.
AB  - Nanostructured zinc-copper mixed ferrite was synthesized using sol-gel method.
      XRD patterns of different compositions of zinc-copper ferrite, Zn(1-x)Cu(x)Fe2O4
      (x = 0.0, 0.25, 0.50, 0.75), revealed single phase inverse spinel ferrite in all
      the samples synthesized. With increasing copper concentration, the crystallite
      size was found to be increased from 28 nm to 47 nm. The surface morphology of all
      the samples studied by the Scanning Electron Microscopy there exhibits porous
      structure of particles throughout the samples. The pellets of the samples are
      prepared for LPG sensing characteristics. The sensing is carried out at different
      operating temperatures (200, 225, and 250 degrees C) with the variation of LPG
      concentrations (0.2, 0.4, and 0.6 vol%). The maximum sensitivity of 55.33% is
      observed at 250 degrees C operating for the 0.6 vol% LPG.

PMID- 23864832
TI  - Effects of low-level autonomic stimulation on prevention of atrial fibrillation
      induced by acute electrical remodeling.
AB  - BACKGROUND: Rapid atrial pacing (RAP) can induce electrical and autonomic
      remodeling and facilitate atrial fibrillation (AF). Recent reports showed that
      low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an
      antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate
      heterogeneity induced by RAP. METHODS AND RESULTS: Mongrel dogs were divided into
      (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial
      sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50%
      below the threshold slowing sinus rate by <= 30 msec. RAP induced a significant
      decrease in effective refractory period (ERP) and increase in the window of
      vulnerability at all sites, characterized by descending and elevated gradient
      differences towards the ganglionic plexi (GP) sites, respectively. The ERP
      dispersion was obviously enlarged by RAP and more significant when the ERP of GP
      related sites was considered. Recovery time from AF was also prolonged
      significantly as a result of RAP. LLVNS could reverse all these changes induced
      by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS
      can reverse the electrical and autonomic remodeling and abolish the GP-central
      gradient differences induced by RAP, and thus it can recover the homogeneous
      substrate, which may be the underlying mechanism of its antiarrhythmic effect.

PMID- 23864834
TI  - Timing and operating mode design for time-gated fluorescence lifetime imaging
      microscopy.
AB  - Steady-state fluorence imaging and time-resolved fluorescence imaging are two
      important areas in fluorescence imaging research. Fluorescence lifetime imaging
      is an absolute measurement method which is independent of excitation laser
      intensity, fluorophore concentration, and photobleaching compared to fluorescence
      intensity imaging techniques. Time-gated fluorescence lifetime imaging microscopy
      (FLIM) can provide high resolution and high imaging frame during mature FLIM
      methods. An abstract time-gated FLIM model was given, and important temporal
      parameters are shown as well. Aiming at different applications of steady and
      transient fluorescence processes, two different operation modes, timing and
      lifetime computing algorithm are designed. High resolution and high frame can be
      achieved by one-excitation one-sampling mode and least square algorithm for
      steady imaging applications. Correspondingly, one-excitation two-sampling mode
      and rapid lifetime determination algorithm contribute to transient fluorescence
      situations. 

PMID- 23864835
TI  - Liquid-liquid equilibrium of poly(ethylene glycol) 6000 + sodium succinate +
      water system at different temperatures.
AB  - Phase diagrams and the compositions of coexisting phases of poly(ethylene glycol)
      (PEG) 6000 + sodium succinate + water system have been determined experimentally
      at 298.15, 308.15, and 318.15 K. The effects of temperature on the binodal curve
      and tie lines have been studied. The binodal curves were successfully fitted to a
      nonlinear equation relating the concentrations of PEG 6000 and sodium succinate,
      and the coefficients were estimated for the formentioned systems (low AARD, high
      R(2), and low SD). Tie-line compositions were estimated and correlated using
      Othmer-Tobias and Bancroft equations, and the parameters were reported. The
      effect of temperature on the phase-forming ability has been studied by fitting
      the binodal data to a Setschenow-type equation for each temperature. The
      effective excluded volume (EEV) values were also calculated from the binodal
      data, and it was found out that the values increased with an increase in the
      temperature. Furthermore, the effect of MW of PEG on the phase diagram has been
      studied and verified.

PMID- 23864836
TI  - Stomatal development in Arabidopsis.
AB  - Stomata consist of two guard cells that function as turgor-operated valves that
      regulate gas exchange in plants. In Arabidopsis, a dedicated cell lineage is
      initiated and undergoes a series of cell divisions and cell-state transitions to
      produce a stoma. A set of basic helix-loop-helix (bHLH) transcription factors
      regulates the transition and differentiation events through the lineage, while
      the placement of stomata relative to each other is controlled by intercellular
      signaling via peptide ligands, transmembrane receptors, and mitogen-activated
      protein kinase (MAPK) modules. Some genes involved in regulating stomatal
      differentiation or density are also involved in hormonal and environmental stress
      responses, which may provide a link between modulation of stomatal development or
      function in response to changes in the environment. Premitotic polarlylocalized
      proteins provide an added layer of regulation, which can be addressed more
      thoroughly with the identification of additional proteins in this pathway.
      Linking the networks that control stomatal development promises to bring advances
      to our understanding of signal transduction, cell polarity, and cell-fate
      specification in plants. 

PMID- 23864837
TI  - Leaf development.
AB  - Leaves are the most important organs for plants. Without leaves, plants cannot
      capture light energy or synthesize organic compounds via photosynthesis. Without
      leaves, plants would be unable perceive diverse environmental conditions,
      particularly those relating to light quality/quantity. Without leaves, plants
      would not be able to flower because all floral organs are modified leaves.
      Arabidopsis thaliana is a good model system for analyzing mechanisms of
      eudicotyledonous, simple-leaf development. The first section of this review
      provides a brief history of studies on development in Arabidopsis leaves. This
      history largely coincides with a general history of advancement in understanding
      of the genetic mechanisms operating during simple-leaf development in
      angiosperms. In the second section, I outline events in Arabidopsis leaf
      development, with emphasis on genetic controls. Current knowledge of six
      important components in these developmental events is summarized in detail,
      followed by concluding remarks and perspectives. 

PMID- 23864839
TI  - Novel Organotin(IV) Schiff Base Complexes with Histidine Derivatives: Synthesis,
      Characterization, and Biological Activity.
AB  - Five novel tin Schiff base complexes with histidine analogues (derived from the
      condensation reaction between L-histidine and 3,5-di-tert-butyl-2
      hydroxybenzaldehyde) have been synthesized and characterized. Characterization
      has been completed by IR and high-resolution mass spectroscopy, 1D and 2D
      solution NMR ((1)H, (13)C  and (119)Sn), as well as solid state (119)Sn NMR. The
      spectroscopic evidence shows two types of structures: a trigonal bipyramidal
      stereochemistry with the tin atom coordinated to five donating atoms (two oxygen
      atoms, one nitrogen atom, and two carbon atoms belonging to the alkyl moieties),
      where one molecule of ligand is coordinated in a three dentate fashion. The
      second structure is spectroscopically described as a tetrahedral tin complex with
      four donating atoms (one oxygen atom coordinated to the metal and three carbon
      atoms belonging to the alkyl or aryl substituents), with one molecule of ligand
      attached. The antimicrobial activity of the tin compounds has been tested against
      the growth of bacteria in vitro to assess their bactericidal properties. While
      pentacoordinated compounds 1, 2, and 3 are described as moderate effective to
      noneffective drugs against both Gram-positive and Gram-negative bacteria,
      tetracoordinated tin(IV) compounds 4 and 5 are considered as moderate effective
      and most effective compounds, respectively, against the methicillin-resistant
      Staphylococcus aureus strains (Gram-positive). 

PMID- 23864838
TI  - The UVR8 UV-B Photoreceptor: Perception, Signaling and Response.
AB  - Ultraviolet-B radiation (UV-B) is an intrinsic part of sunlight that is
      accompanied by significant biological effects. Plants are able to perceive UV-B
      using the UV-B photoreceptor UVR8 which is linked to a specific molecular
      signaling pathway and leads to UV-B acclimation. Herein we review the biological
      process in plants from initial UV-B perception and signal transduction through to
      the known UV-B responses that promote survival in sunlight. The UVR8 UV-B
      photoreceptor exists as a homodimer that instantly monomerises upon UV-B
      absorption via specific intrinsic tryptophans which act as UV-B chromophores. The
      UVR8 monomer interacts with COP1, an E3 ubiquitin ligase, initiating a molecular
      signaling pathway that leads to gene expression changes. This signaling output
      leads to UVR8-dependent responses including UV-B-induced photomorphogenesis and
      the accumulation of UV-B-absorbing flavonols. Negative feedback regulation of the
      pathway is provided by the WD40-repeat proteins RUP1 and RUP2, which facilitate
      UVR8 redimerization, disrupting the UVR8-COP1 interaction. Despite rapid
      advancements in the field of recent years, further components of UVR8 UV-B
      signaling are constantly emerging, and the precise interplay of these and the
      established players UVR8, COP1, RUP1, RUP2 and HY5 needs to be defined. UVR8 UV-B
      signaling represents our further understanding of how plants are able to sense
      their light environment and adjust their growth accordingly. 

PMID- 23864840
TI  - Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth
      Factor Receptor Tyrosine Kinase Inhibitor.
AB  - Since the first description of non-small cell lung cancer (NSCLC) with activating
      epidermal growth factor receptor (EGFR) mutation as a distinct clinical entity,
      studies have proved EGFR tyrosine kinase inhibitors (TKIs) as a first choice of
      treatment. The median response duration of TKIs as a first-line treatment for
      EGFR mutant tumors ranges from 11 to 14 months. However, acquired resistance to
      EGFR-TKIs is inevitable due to various mechanisms, such as T790M, c-Met
      amplification, activation of alternative pathways (IGF-1, HGF, PI3CA, AXL),
      transformation to mesenchymal cell or small cell features, and tumor
      heterogeneity. Until development of a successful treatment strategy to overcome
      such acquired resistance, few options are currently available. Here we provide a
      summary of the therapeutic options after failure of first line EGFR-TKI treatment
      for NSCLC. 

PMID- 23864841
TI  - Trends in Cancer Screening Rates among Korean Men and Women: Results from the
      Korean National Cancer Screening Survey, 2004-2012.
AB  - PURPOSE: The Korean National Cancer Screening Survey (KNCSS), a nationwide,
      annual cross-sectional survey, has been conducted since 2004. The current study
      was conducted in order to report on trends in cancer screening rates for five
      types of cancer (stomach, liver, colorectal, breast, and cervix uteri). MATERIALS
      AND METHODS: KNCSS data were collected between 2004 and 2012. The eligible study
      population included cancer-free men who were 40 years of age and older and women
      who were 30 years of age and older. The lifetime screening rate, screening rate
      with recommendation, and changes in annual rates were calculated. RESULTS:
      Lifetime screening rates and screening rates with recommendation for the five
      types of cancer rose steadily until 2010, showed a slight drop or were stable in
      2011, and increased again in 2012. On average, screening rates with
      recommendation have shown annual increases of 4.3% (95% confidence interval [CI],
      3.6 to 5.0%) for stomach cancer, 0.8% (95% CI, -0.5 to 2.1%) for liver cancer,
      2.4% (95% CI, 1.3 to 3.5%) for colorectal cancer, 4.5% (95% CI, 3.9 to 5.1%) for
      breast cancer, and 1.3% (95% CI, 0.6 to 2.0%) for cervical cancer. Disparities in
      age groups and household incomes have been decreasing since 2004. CONCLUSION:
      Cancer screening rates in Korea showed a significant increase from 2004 to 2012,
      and screening rates for gastric and breast cancer are now approaching 70%. The 10
      Year Plan for Cancer Control target for screening rates was met or nearly met for
      all cancer types examined, with the exception of liver and colorectal cancer.

PMID- 23864842
TI  - Predicting Survival in Patients with Advanced Non-squamous Non-small Cell Lung
      Cancer: Validating the Extent of Metastasis.
AB  - PURPOSE: A number of factors related to overall survival (OS) have been addressed
      in advanced non-small cell lung cancer (NSCLC). This study was conducted to
      determine the impact of whole-body metastatic regions on survival outcome in
      advanced non-squamous NSCLC. MATERIALS AND METHODS: Between March 2005 and
      February 2011, 112 eligible patients with newly confirmed stage IV non-squamous
      NSCLC, available for epidermal growth factor receptor (EGFR) mutation status 18
      21 analysis, and accessible for the determination of pretreatment whole-body
      metastatic regions were enrolled in this retrospective study. The total number of
      synchronous metastatic regions was scored according to the following disease
      sites: abdomen/pelvis, lung to lung/pulmonary lymphangitic spread, bone,
      pleura/pleural effusion/pericardial effusion, neck/axillary lymph nodes, other
      soft tissue, brain. RESULTS: The median age of the cohort was 65 years (range, 31
      to 88 years). The median whole-body metastatic score was 2 (range, 1 to 6), and
      bone and lung to lung were the most common metastatic sites. EGFR mutations were
      observed in 40 (35.7%) patients with a deletion in exon 19 and Leu858Arg mutation
      in exon 21 being detected in 16 (40.0%) and 19 (47.5%) patients, respectively.
      Multivariate analysis for OS revealed that treatment factors (p=0.005),
      performance status (p=0.006), whole-body metastatic score (p<0.001), and EGFR
      mutation status (p=0.095) were significantly or marginally associated with OS.
      CONCLUSION: The results of the present study demonstrated that whole-body
      metastatic extent strongly affects survival outcome, even after adjustment for
      other significant variables in advanced non-squamous NSCLC. The clinical validity
      of more curative multimodal approaches in cohorts with limited metastases remains
      to be explored.

PMID- 23864843
TI  - Which patients might benefit from postmastectomy radiotherapy in breast cancer
      patients with t1-2 tumor and 1-3 axillary lymph nodes metastasis?
AB  - PURPOSE: This study compared the clinical outcomes of T1-2N1 breast cancer
      patients with and without postmastectomy radiotherapy (PMRT). Risk factors for
      loco-regional recurrence (LRR) were identified in order to define a subgroup of
      patients who might benefit from PMRT. MATERIALS AND METHODS: Of 110 T1-2N1 breast
      cancer patients who underwent mastectomy from January 1994 through December 2009,
      32 patients underwent PMRT and 78 patients did not. Treatment outcomes and risk
      factors for LRR were analyzed. RESULTS: The 5- and 10-year LRR rates were both
      6.2% in the PMRT group, and 10.4% and 14.6% in the no-PMRT group (p=0.336). In
      addition, no significant differences in distant metastasis-free survival (DMFS)
      or overall survival (OS) were observed between patients receiving and not
      receiving PMRT. In multivariate analysis, factors associated with higher LRR
      rates included grade 3 disease, extracapsular extension (ECE), and triple
      negative subtype. Patients who had one or more risk factors for LRR were defined
      as a high-risk patient group. In the high-risk group, both 5- and 10-year LRR
      rates for patients who underwent PMRT was 18.2%, and LRR rates of 21.4% at five
      years and 36.6% at 10 years were observed for patients who did not undergo PMRT
      (p=0.069). CONCLUSION: PMRT in T1-2N1 breast cancer patients should be considered
      according to several prognostic factors in addition to T and N stage. Findings of
      our study indicated that PMRT did not improve LRR, DMFS, or OS in T1-2N1 breast
      cancer patients. However, in a subgroup of patients with grade 3 disease, ECE, or
      triple negative subtype, PMRT might be beneficial.

PMID- 23864844
TI  - Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell
      Lymphoma Patients with Bone Marrow Involvement.
AB  - PURPOSE: We investigated the clinical outcome of bone marrow (BM) involvement in
      patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based
      therapy. MATERIALS AND METHODS: A total of 567 consecutive patients with newly
      diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and
      March 2010 were included in the current study. All of the patients underwent a BM
      study at the initial staging and the clinical characteristics and prognosis of
      these patients with or without BM involvement were analyzed retrospectively.
      RESULTS: The total cohort included 567 patients. The overall incidence of BM
      involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1
      to 80.7 months) for patients who were alive at the last follow-up, the five-year
      overall survival (OS) and event-free survival (EFS) rate in patients without BM
      involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in
      patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate
      analysis, among total patients, BM involvement showed a significant association
      with OS and EFS. In univariate and multivariate analyses, even among stage IV
      patients, a significant association with worse EFS was observed in the BM
      involvement group. CONCLUSION: BM involvement at diagnosis affected the survival
      of patients with DLBCL who received RCHOP. Although use of RCHOP can result in
      significant improvement of the therapeutic effect of DLBCL, BM involvement is
      still a negative prognostic factor of DLBCL patients in the era of rituximab.

PMID- 23864845
TI  - Expression of Transforming Growth Factor beta1 and E-Cadherin Proteins in
      Pulmonary Adenocarcinoma: Its Significance in Tumor Progression.
AB  - PURPOSE: This study was conducted in order to investigate the significance of
      transforming growth factor beta1 (TGFbeta1) and E-cadherin proteins in tumor
      progression of lung adenocarcinoma and to evaluate their differential expression
      in association with morphologic characteristics. MATERIALS AND METHODS: A total
      of 65 pulmonary adenocarcinomas were reclassified according to the new
      classification system proposed by the International Association for the Study of
      Lung Cancer, American Thoracic Society, and European Respiratory Society. Tumor
      samples from 20 adenocarcinomas in situ (AIS, formerly bronchioloalveolar
      carcinoma [BAC]), 9 minimally invasive adenocarcinomas (MIA, formerly BAC with <=
      5 mm invasion), 17 lepidic predominant adenocarcinomas (LPA, formerly mixed
      adenocarcinoma showing nonmucinous BAC features with >5 mm invasion), and 19
      invasive adenocarcinomas with no BAC features were analyzed by
      immunohistochemistry for expression of TGFbeta1 and E-cadherin proteins. RESULTS:
      TGFbeta1 expression was detected in 46% (21/46) of noninvasive elements and 87%
      (39/45) of invasive elements (p=0.001). E-Cadherin expression was less frequent
      in invasive components than in noninvasive components (38% vs. 65%, p=0.009).
      Negative correlation was identified between TGFbeta1 expression and E-cadherin
      expression in noninvasive elements (p=0.022). More importantly, significantly
      higher frequency of TGFbeta1 expression was observed in noninvasive components of
      LPA (14/17, 82%), compared with those of either AIS (5/20, 25%) or MIA (2/9, 22%)
      (p=0.008). CONCLUSION: Our data indicate involvement of both TGFbeta1 and E
      cadherin proteins in tumor progression of pulmonary adenocarcinoma. It is
      noteworthy that TGFbeta1 up-regulation precedes alveolar destruction by invasion
      of tumor cells. TGFbeta1 may thus have the potential to improve lung
      adenocarcinoma diagnostics and therapeutics.

PMID- 23864846
TI  - Src Family Kinase Inhibitor PP2 Has Different Effects on All-Trans-Retinoic Acid
      or Arsenic Trioxide-Induced Differentiation of an Acute Promyelocytic Leukemia
      Cell Line.
AB  - PURPOSE: Leukemic promyelocytes have the unique ability to undergo
      differentiation after exposure to retinoic acid and both differentiation and
      apoptosis after exposure to arsenic trioxide (ATO). Recent studies have shown
      that inhibition of Src family kinases (SFKs) resulted in enhancement of retinoic
      acid-induced myeloid differentiation. MATERIALS AND METHODS: In this study, we
      investigated the question of whether the SFK inhibitor PP2 enhanced the
      differentiation of NB4 cells when combined with ATO as well as when combined with
      all-trans-retinoic acid (ATRA). In addition, we attempted to determine the
      difference in retinoic acid-induced gene expression between cells treated with
      PP2 in combination with ATRA and in combination with ATO. RESULTS: SFK inhibitor
      PP2 induced significant enhancement of ATRA- or ATO-induced differentiation of
      NB4 cells. A significantly stronger synergistic effect was observed when PP2 was
      combined with ATRA than when combined with ATO. Flow cytometric analysis
      demonstrated a significant increase in CD11b-positive granulocytes up to 60.73%
      and 31.58%, respectively. These results were confirmed by nitroblue tetrazolium
      staining. These effects were not related to apoptosis. Results of Annexin-V
      fluorescein staining revealed that PP2 combined with ATRA or PP2 combined with
      ATO did not induce apoptosis in NB4 cells. Retinoic acid-induced gene expression
      was different in both groups. Intercellular adhesion molecule-1 expression showed
      a significant increase in cells treated with PP2 in combination with ATRA,
      whereas cathepsin D expression showed a significant increase in cells treated
      with PP2 in combination with ATO. CONCLUSION: Our data showed that SFK inhibitor
      PP2 enhanced acute promyelocytic leukemia cell differentiation when combined with
      either ATRA or ATO with difference in activation of retinoic acid-induced genes.

PMID- 23864847
TI  - RASSF1A Suppresses Cell Migration through Inactivation of HDAC6 and Increase of
      Acetylated alpha-Tubulin.
AB  - PURPOSE: The RAS association domain family protein 1 (RASSF1) has been implicated
      in a tumor-suppressive function through the induction of acetylated alpha-tubulin
      and modulation of cell migration. However, the mechanisms of how RASSF1A is
      associated with acetylation of alpha-tubulin for controlling cell migration have
      not yet been elucidated. In this study, we found that RASSF1A regulated cell
      migration through the regulation of histon deacetylase 6 (HDAC6), which functions
      as a tubulin deacetylase. MATERIALS AND METHODS: The cell migration was assessed
      using wound-healing and transwell assays. The role of RASSF1A on cell migration
      was examined by immunofluorescence staining, HDAC activity assay and western blot
      analysis. RESULTS: Cell migration was inhibited and cell morphology was changed
      in RASSF1A-transfected H1299 cells, compared with controls, whereas HDAC6 protein
      expression was not changed by RASSF1A transfection in these cells. However,
      RASSF1A inhibited deacetylating activity of HDAC6 protein and induced acetylated
      alpha-tubulin expression. Furthermore, acetylated alpha-tubulin and HDAC6 protein
      were co-localized in the cytoplasm in RASSF1A-transfected H1299 cells.
      Conversely, when the endogenous RASSF1A expression in HeLa cells was blocked with
      RASSF1A siRNA treatment, acetylated alpha-tubulin was co-localized with HDAC6
      protein throughout the whole cells, including the nucleus, compared with scramble
      siRNA-treated HeLa cells. The restoration of RASSF1A by 5-Aza-dC treatment also
      induced acetylated alpha-tubulin through inhibition of HDAC6 activity that
      finally resulted in suppressing cell migration in H1299 cells. To further confirm
      the role of HDAC6 in RASSF1A-mediated cell migration, the HDAC6 expression in
      H1299 cells was suppressed by using HDAC6 siRNA, and cell motility was found to
      be decreased through enhanced acetylated alpha-tubulin. CONCLUSION: The results
      of this study suggest that the inactivation of HDAC6 by RASSF1A regulates cell
      migration through increased acetylated alpha-tubulin protein.

PMID- 23864848
TI  - Two cases of humoral hypercalcemia of malignancy in metastatic
      cholangiocarcinoma.
AB  - Humoral hypercalcemia of malignancy (HHM) is rarely associated with
      cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was
      admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM
      associated with locally advanced CC. As the tumor responded to the concurrent
      chemoradiotherapy with capecitabine and cisplatin, serum calcium level was
      normalized. However, according to the disease progression, he suffered recurrence
      of HHM and he expired approximately one year after initial diagnosis. A 68-year
      old male who presented with abdominal pain was diagnosed with metastatic CC.
      After the eighth cycle of gemcitabine and cisplatin, progression of the disease
      was found with HHM. He was treated with the best supportive care, until his
      demise approximately one month after the diagnosis of HHM. We report on two cases
      of HHM associated with CC that demonstrate strong correlation between
      hypercalcemia and disease burden. 

PMID- 23864849
TI  - Multiple cardiac metastases from a nonfunctioning pancreatic neuroendocrine
      tumor.
AB  - Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms, which most commonly
      metastasize to the liver. However, intrathoracic metastases from pNETs are
      encountered infrequently. This report describes a case of nonfunctioning pNET
      with multiple cardiac metastases. A 56-year-old male presented with a palpable
      abdominal mass that showed progressive enlargement. Findings on computed
      tomography (CT) of the abdomen revealed two relatively well-marginated
      inhomogeneous low-attenuation masses, one in the head of the pancreas and the
      other in the tail. Multiple enhancing masses in the left pericardium with
      myocardial involvement were observed on chest CT and transthoracic
      echocardiography. Needle biopsies were performed on the mass in the tail of the
      pancreas and the left ventricular apical pericardium; histologic examination by
      hematoxylin and eosin morphology and immunohistochemical staining showed pNET in
      both. This is the first report of pNET with multiple cardiac metastases to
      previously undescribed metastatic sites. 

PMID- 23864850
TI  - Detection of the enterotoxigenic genes (sei,sej) in Staphylococcus aureus
      isolates from bovine mastitis milk in the West Azerbaijan of Iran.
AB  - Staphylococcus aureus is a major causative pathogen of clinical and subclinical
      mastitis of dairy domestic ruminants. This organism produces a variety of
      extracellular toxins and virulence factors such as enterotoxin SEI and SEJ that
      contribute to its pathogenic potential. In this study 25 S. aureus isolates
      obtained from four dairy herds of Urmia region which is located in West
      Azerbaijan province in Iran. The tested isolates were identified on the basis of
      the cultural and biochemical properties, as well as amplification of the aroA
      gene which is specific for S. aureus. All isolates were also analyzed for the
      presence of the SEI (sei) and SEJ (sej) encoding genes using polymerase chain
      reaction (PCR). Seven positive isolates were detected for sei, but sej gene was
      not detected in any of the total number of 25 isolates. The present study
      revealed that the PCR amplification of the aroA gene could be used as a powerful
      tool for identification of S. aureus from the cases of bovine mastitis. Results
      of the present study also showed that the strains of S. aureus which cause
      mastitis can potentially produce enterotoxin SEI. Overall, our results suggest
      that it is of special importance to follow the presence of enterotoxin-producing
      S. aureus in other dairy products, especially for protecting the consumers from
      staphylococcal food poisoning.

PMID- 23864851
TI  - Learned shrinkage approach for low-dose reconstruction in computed tomography.
AB  - We propose a direct nonlinear reconstruction algorithm for Computed Tomography
      (CT), designed to handle low-dose measurements. It involves the filtered back
      projection and adaptive nonlinear filtering in both the projection and the image
      domains. The filter is an extension of the learned shrinkage method by Hel-Or and
      Shaked to the case of indirect observations. The shrinkage functions are learned
      using a training set of reference CT images. The optimization is performed with
      respect to an error functional in the image domain that combines the mean square
      error with a gradient-based penalty, promoting image sharpness. Our numerical
      simulations indicate that the proposed algorithm can manage well with noisy
      measurements, allowing a dose reduction by a factor of 4, while reducing noise
      and streak artifacts in the FBP reconstruction, comparable to the performance of
      a statistically based iterative algorithm. 

PMID- 23864852
TI  - Psoriasis Patients' Knowledge about the Disease and Treatments.
AB  - Patients' knowledge about psoriasis and its treatment has been randomly studied
      previously. The aim of the study is to investigate patients' knowledge about
      psoriasis in relation to undergoing patient education in the context of climate
      therapy (CT). The psoriasis knowledge questionnaire (PKQ) was used in a follow-up
      pre-post study design of Norwegian patients with psoriasis at the age of 20 years
      and older undergoing CT at Gran Canaria (Spain). Patients completed the PKQ and
      provided selected demographic, clinical and health information before (T1),
      immediately after (T2), and 3 months after (T3) CT. Disease severity was assessed
      using the psoriasis area and severity index (PASI). 254 psoriasis patients were
      included (74%). The PKQ score improved significantly from T1 to T2 and T3 (P <
      0.001 for both comparisons). Although patient's knowledge improved, further
      research should use gold standard designs (experiments) to study the effects of
      educational interventions in different contexts. 

PMID- 23864853
TI  - Protective Effect of Acacia nilotica (L.) against Acetaminophen-Induced
      Hepatocellular Damage in Wistar Rats.
AB  - The potential biological functions of A. nilotica have long been described in
      traditional system of medicine. However, the protective effect of A. nilotica on
      acetaminophen-induced hepatotoxicity is still unknown. The present study
      attempted to investigate the protective effect of A. nilotica against
      acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver
      functional tests Alanine transaminase (ALT), Aspartate transaminase (AST),
      Alkaline phosphatase (ALP), total bilirubin, total protein, oxidative stress test
      (Lipid peroxidation), antioxidant parameter glutathione (GSH), and
      histopathological changes were examined. Our results show that the pretreatment
      with A. nilotica (250 mg/kg.bw) orally revealed attenuation of serum activities
      of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by
      administration of acetaminophen. Further, pretreatment with extract elevated the
      total protein and GSH level and decreased the level of LPO. Histopathological
      analysis confirmed the alleviation of liver damage and reduced lesions caused by
      acetaminophen. The present study undoubtedly provides a proof that
      hepatoprotective action of A. nilotica extract may rely on its effect on reducing
      the oxidative stress in acetaminophen-induced hepatic damage in rat model. 

PMID- 23864854
TI  - Attracting Child Psychiatrists to a Televideo Consultation Service: The TeleLink
      Experience.
AB  - Objective. Identify aspects of psychiatry work that are rewarding, as well as
      those that are challenging, from the perspective of psychiatrists and residents
      participating in televideo consultation services. Method. A web-based survey was
      distributed to psychiatrists within the Division of Child Psychiatry at the
      University of Toronto. Also, semistructured interviews were conducted with six
      child psychiatrists providing services to a telepsychiatry program. Finally, a
      focus group interview was held with four psychiatry residents. Results. Child
      psychiatrists are very comfortable conducting assessments via televideo. Factors
      identified as being important in the decision to participate in telepsychiatry
      include assisting underserved communities, supportive administrative staff,
      enhanced rural provider capacity, financial incentives, and convenience. The
      study's qualitative phase identified four themes in the decision to participate
      in telepsychiatry: (1) organizational, (2) shared values, (3) innovation, and (4)
      the consultation model. Conclusion. The success of televideo consultation
      programs in attracting child psychiatrists to provide consultation services to
      underresourced communities makes an important contribution to psychiatric
      workforce shortages. Understanding what aspects of telepsychiatry are most
      appreciated by consulting psychiatrists and residents offers useful strategies to
      telepsychiatry administrators and medical school educators seeking to attract,
      train, and retain psychiatry practitioners. 

PMID- 23864855
TI  - A multilevel gamma-clustering layout algorithm for visualization of biological
      networks.
AB  - Visualization of large complex networks has become an indispensable part of
      systems biology, where organisms need to be considered as one complex system. The
      visualization of the corresponding network is challenging due to the size and
      density of edges. In many cases, the use of standard visualization algorithms can
      lead to high running times and poorly readable visualizations due to many edge
      crossings. We suggest an approach that analyzes the structure of the graph first
      and then generates a new graph which contains specific semantic symbols for
      regular substructures like dense clusters. We propose a multilevel gamma
      clustering layout visualization algorithm (MLGA) which proceeds in three
      subsequent steps: (i) a multilevel gamma -clustering is used to identify the
      structure of the underlying network, (ii) the network is transformed to a tree,
      and (iii) finally, the resulting tree which shows the network structure is drawn
      using a variation of a force-directed algorithm. The algorithm has a potential to
      visualize very large networks because it uses modern clustering heuristics which
      are optimized for large graphs. Moreover, most of the edges are removed from the
      visual representation which allows keeping the overview over complex graphs with
      dense subgraphs. 

PMID- 23864856
TI  - A study on bone mass in elderly chinese foot-binding women.
AB  - The aim of this study is to understand the influences of the social custom of
      foot binding on female osteoporosis by means of comparing and analyzing the
      lumbar vertebrae and hip bone mass differences between the foot-binding aged
      women and unbound women of the same age at Qujing District of Yunnan Province. Of
      the examined people, 81.37% suffer from osteoporosis on the basis of lumbar
      vertebra (L1-L4) and femoral neck BMD, of which 82.14% for the foot-binding group
      and 80.44% for the unbound group. There is no statistical difference for the
      osteoporosis morbidity of the two groups. Compare the BMD value for various
      vertebrae, femoral neck, and rehabilitation of the two groups and find the BMD
      value for the other parts have no statistical difference except the BMD value of
      L1 centrum, which shows that foot binding does not significantly influence the
      overall bone mineral density of foot-binding women. 

PMID- 23864857
TI  - Delay in diagnosis of adrenal insufficiency is a frequent cause of adrenal
      crisis.
AB  - Delay of diagnosis of primary adrenal insufficiency (PAI) leads to adrenal crisis
      which is potentially lethal complication. The objective of our work was an
      assessment whether the establishment of diagnosis of adrenocortical insufficiency
      in Poland is so much delayed as assessed in the past. We have analysed data from
      60 patients with diagnosis of PAI established in our department during the past
      12 years and who are still under our care. We found that the time to diagnosis of
      primary adrenal insufficiency in Poland exceeds 3 months in every patient and 6
      months in patients admitted with symptoms of adrenal crisis. Forty-four percent
      of patients were diagnosed only just after the hospitalisation due to crisis,
      despite the evident signs and symptoms of PAI. Lack of appetite and loss of body
      weight occurred in all patients and for that reason a diagnosis of chronic
      gastric and duodenal ulcer disease was the most often incorrect diagnosis. After
      the proper diagnosis and treatment, in the course of 1-11 years of observation,
      there was only 6 imminent adrenal crises in 5 patients. Our results indicated
      that training of primary care physicians in the field of recognising and
      treatment of adrenal insufficiency is still essential. 

PMID- 23864858
TI  - Epidemiological study of the incidence of cancers eligible for proton or carbon
      ions therapy: methodology and results of recruitment estimation.
AB  - Context. Hadrontherapy is an innovative form of radiotherapy using beams of
      protons or carbon ions able to destroy some radio-resistant tumours. Because
      these tumours are highly specific amongst all cancerous tumours, it is impossible
      to determine the incidence of these diseases from surveillance registries. Goal.
      To assess, within the Rhone-Alpes region, the incidence of cancers being
      hadrontherapy indications. Method. Prospective, multicentre continuous data
      collection during 1 year, by practitioners participating to multidisciplinary
      tumor board. Tumours are inoperable, radio resistant, at primary stage of
      development, or locally recurrent, with low metastatic potential. Results. Study
      involved 27 healthcare centres, 52 groups of specialist practitioners. The
      estimated incidence of cancers eligible for hadrontherapy in the Rhone-Alpes
      region in 2010, that is, for 34 locations in all, is of 8.5/100 000 inhabitants.
      Appraisal of the low potential of metastatic progression is impeded, because
      these are rare diseases, whose outcome is unfamiliar to investigators.
      Conclusion. Future epidemiological studies will need to focus on prognosis and on
      the metastatic progression rate of these diseases. Indeed, there are few
      information available on this subject in the literature that could be used to
      improve preventive measures, medical care, and the surveillance of these rare
      cancers. 

PMID- 23864859
TI  - Metabolism and cancer: old and new players.

PMID- 23864860
TI  - Interaction of Wnt Signaling with BMP/Smad Signaling during the Transition from
      Cell Proliferation to Myogenic Differentiation in Mouse Myoblast-Derived Cells.
AB  - Background. Wnt signaling is involved in muscle formation through beta-catenin
      dependent or -independent pathways, but interactions with other signaling
      pathways including transforming growth factor beta/Smad have not been precisely
      elucidated. Results. As Wnt4 stimulates myogenic differentiation by antagonizing
      myostatin (GDF8) activity, we examined the role of Wnt4 signaling during muscle
      differentiation in the C2C12 myoblast cell line. Among several extrinsic
      signaling molecules examined in a microarray analysis of C2C12 cells during the
      transition from cell proliferation to differentiation after mitogen deprivation,
      bone morphogenetic protein 4 (BMP4) expression was prominently increased. Wnt4
      overexpression had similar effects on BMP4 expression. BMP4 was able to inhibit
      muscle differentiation when added to the culture medium. BMP4 and noggin had no
      effects on the cellular localization of beta-catenin induced by Wnt3a; however,
      the BMP4-induced phosphorylation of Smad1/5/8 was enhanced by Wnt4, but not by
      Wnt3a. The BMP antagonist noggin effectively stimulated muscle differentiation
      through binding to endogenous BMPs, and the effect of noggin was enhanced by the
      presence of Wnt3a and Wnt4. Conclusion. These results suggest that BMP/Smad
      pathways are modified through Wnt signaling during the transition from progenitor
      cell proliferation to myogenic differentiation, although Wnt/beta-catenin
      signaling is not modified with BMP/Smad signaling. 

PMID- 23864861
TI  - Contemporary clinical management of endometrial cancer.
AB  - Although the contemporary management of endometrial cancer is straightforward in
      many ways, novel data has emerged over the past decade that has altered the
      clinical standards of care while generating new controversies that will require
      further investigation. Fortunately most cases are diagnosed at early stages, but
      high-risk histologies and poorly differentiated tumors have high metastatic
      potential with a significantly worse prognosis. Initial management typically
      requires surgery, but the role and extent of lymphadenectomy are debated
      especially with well-differentiated tumors. With the changes in surgical staging,
      prognosis correlates more closely with stage, and the importance of cytology has
      been questioned and is under evaluation. The roles of radiation in intermediate
      risk patients and chemotherapy in high-risk patients are emerging. The
      therapeutic index of brachytherapy needs to be considered, and the best
      sequencing of combined modalities needs to balance efficacy and toxicities.
      Additionally novel targeted therapies show promise, and further studies are
      needed to determine the appropriate use of these new agents. Management of
      endometrial cancer will continue to evolve as clinical trials continue to answer
      unsolved clinical questions. 

PMID- 23864863
TI  - Pneumothorax following ERCP: Report of Two Cases with Different Pathophysiology.
AB  - In the last thirty years, the widespread use of endoscopic retrograde
      cholangiopancreatography (ERCP) has radically changed the management of patients
      with diseases of the extrahepatic biliary tract and pancreas. Pneumothorax is a
      rare complication of ERCP. We report two cases of pneumothorax following elective
      ERCP for ductal stone clearance. The first patient was a 45-year-old female, who
      developed respiratory distress, abdominal pain, and profoundly abdominal
      distention immediately after the procedure. Imaging studies revealed the presence
      of a right-side pneumothorax, pneumomediastinum, pneumoperitoneum, and
      pneumoretroperitoneum. The second patient was a 94-year-old female, who developed
      tension pneumothorax with clinical signs of shock during the procedure. Imaging
      studies revealed the presence of a right-side pneumothorax without free air in
      the mediastinum and retroperitoneal space. The imaging findings suggest that the
      occurrence of this rare complication in our patients was caused by entirely
      different pathophysiological mechanisms. Both patients were successfully treated
      with chest tube insertion, and no further intervention was required. Clinicians
      should be aware of this serious complication because delayed diagnosis may
      involve significant morbidity and mortality risks. 

PMID- 23864862
TI  - Intrauterine growth restriction: effects of physiological fetal growth
      determinants on diagnosis.
AB  - The growth of the fetus, which is strongly associated with the outcome of
      pregnancy, reflects interplay of several physiological and pathological factors.
      The assessment of fetal growth is based on comparison of birthweight (BW) or
      estimated fetal weight (EFW) to standards which define reference ranges at a
      spectrum of gestational ages. Most birthweight standards do not take into account
      effects of physiological determinants of fetal growth. Additionally, gestational
      age in many standards is based on the menstrual history and is often inaccurate.
      Fetal growth norms should be based on an early ultrasound estimate of gestational
      age. Customized standards, which have included only ultrasound-dated pregnancies,
      seem to be superior to population-based birthweight norms in predicting perinatal
      mortality and morbidity. Adjustment for individual variation in customized growth
      curves reduces false-positive diagnosis of IUGR and may lead to a very
      significant reduction in intervention for suspected IUGR. Customized growth
      potential identifies better the risk for adverse outcome than the currently used
      national standards, but customized charts may fail in detecting growth-restricted
      stillbirth. An individual's birthweight is the sum of physiological and
      pathological influences operating during pregnancy. Growth potential norms are a
      better discriminator of aberrations of fetal growth than population, ultrasound,
      and customized norms. 

PMID- 23864864
TI  - Immunohistochemical character of hepatic angiomyolipoma: for its management.
AB  - Hepatic angiomyolipoma (AML) is notoriously difficult to diagnose without an
      invasive surgery even with the recent development of the various imaging
      modalities. Additionally, recent reports showed its malignant behavior after the
      surgery; it is important to diagnose the character of each tumor including the
      possible malignant potential and determine the postoperative management for each
      case. For this purpose, we have reviewed reports and focused on the
      immunohistochemical staining with p53 and ki67 of the tumors showing the
      representative case of 60-year-old female. The imaging study of her tumor showed
      the character similar to the hepatocellular carcinoma, and she underwent the
      hepatectomy. The resected tumor stained positive for HMB-45 that is a marker of
      the AML, and 30-50% of the tumor cells were positively stained with Ki67 that is
      a mitotic marker. Also, the atypical epithelioid cells displayed p53
      immunoreactivity. These results suggest the malignant potential of our tumor
      based on the previous reports; therefore the careful followup for this case is
      necessary for a long period whether it shows metastasis, sizing up, and so forth.

PMID- 23864865
TI  - The cannabinoid receptor type 1 is essential for mesenchymal stem cell survival
      and differentiation: implications for bone health.
AB  - Significant loss of bone due to trauma, underlying metabolic disease, or lack of
      repair due to old age surpasses the body's endogenous bone repair mechanisms.
      Mesenchymal stem cells (MSCs) are adult stem cells which may represent an ideal
      cell type for use in cell-based tissue engineered bone regeneration strategies.
      The body's endocannabinoid system has been identified as a central regulator of
      bone metabolism. The aim of the study was to elucidate the role of the
      cannabinoid receptor type 1 in the differentiation and survival of MSCs. We show
      that the cannabinoid receptor type 1 has a prosurvival function during acute cell
      stress. Additionally, we show that the phytocannabinoid, Delta(9)
      Tetrahydrocannabinol, has a negative impact on MSC survival and osteogenesis.
      Overall, these results show the potential for the modulation of the cannabinoid
      system in cell-based tissue engineered bone regeneration strategies whilst
      highlighting cannabis use as a potential cause for concern in the management of
      orthopaedic patients. 

PMID- 23864867
TI  - Detection of the Hematopoietic Stem and Progenitor Cell Marker CD133 during
      Angiogenesis in Three-Dimensional Collagen Gel Culture.
AB  - We detected the hematopoietic stem and progenitor cell marker CD133 using
      immunogold labeling during angiogenesis in a three-dimensional collagen gel
      culture. CD133-positive cells were present in capillary tubes newly formed from
      aortic explants in vitro. The CD133-positive cell population had the capacity to
      form capillary tubes. Lovastatin strongly inhibited cell migration from aortic
      explants and caused the degradation of the capillary tubes. The present study
      provides insight into the function of CD133 during angiogenesis as well as an
      explanation for the antiangiogenic effect of statins. 

PMID- 23864866
TI  - The Necessity of a Systematic Approach for the Use of MSCs in the Clinical
      Setting.
AB  - Cell therapy has emerged as a potential therapeutic strategy in regenerative
      disease. Among different cell types, mesenchymal stem/stromal cells have been
      wildly studied in vitro, in vivo in animal models and even used in clinical
      trials. However, while clinical applications continue to increase markedly, the
      understanding of their physiological properties and interactions raises many
      questions and drives the necessity of more caution and supervised strategy in
      their use. 

PMID- 23864868
TI  - Ecological study on hospitalizations for cancer, cardiovascular, and respiratory
      diseases in the industrial area of Etang-de-Berre in the South of France.
AB  - The Etang-de-Berre area is a large industrialized area in the South of France,
      exposing 300,000 inhabitants to the plumes of its industries. The possible
      associated health risks are of the highest concern to the population, who asked
      for studies investigating their health status. A geographical ecological study
      based on standardized hospitalizations ratios for cancer, cardiovascular, and
      respiratory diseases was carried out over the 2004-2007 period. Exposure to air
      pollution was assessed using dispersion models coupled with a geographic
      information system to estimate an annual mean concentration of sulfur dioxide
      (SO2) for each district. Results showed an excess risk of hospitalization for
      myocardial infarction in women living in districts with medium or high SO2
      exposure, respectively, 38% [CI 95% 4 : 83] and 54% [14 : 110] greater than women
      living in districts at the reference level exposure. A 26% [2 : 57] excess risk
      of hospitalization for myocardial infarction was also observed in men living in
      districts with high SO2 levels. No excess risk of hospitalization for respiratory
      diseases or for cancer was observed, except for acute leukemia in men only.
      Results illustrate the impact of industrial air pollution on the cardiovascular
      system and call for an improvement of the air quality in the area.

PMID- 23864869
TI  - Joy, exercise, enjoyment, getting out: a qualitative study of older people's
      experience of cycling in Sydney, Australia.
AB  - INTRODUCTION: Cycling can be an enjoyable way to meet physical activity
      recommendations and is suitable for older people; however cycling participation
      by older Australians is low. This qualitative study explored motivators,
      enablers, and barriers to cycling among older people through an age-targeted
      cycling promotion program. METHODS: Seventeen adults who aged 50-75 years
      participated in a 12-week cycling promotion program which included a cycling
      skills course, mentor, and resource pack. Semistructured interviews at the
      beginning and end of the program explored motivators, enablers, and barriers to
      cycling. RESULTS: Fitness and recreation were the primary motivators for cycling.
      The biggest barrier was fear of cars and traffic, and the cycling skills course
      was the most important enabler for improving participants' confidence. Reported
      outcomes from cycling included improved quality of life (better mental health,
      social benefit, and empowerment) and improved physical health. CONCLUSIONS: A
      simple cycling program increased cycling participation among older people. This
      work confirms the importance of improving confidence in this age group through a
      skills course, mentors, and maps and highlights additional strategies for
      promoting cycling, such as ongoing improvement to infrastructure and advertising.

PMID- 23864870
TI  - Antibacterial activity of endemic Satureja Khuzistanica Jamzad essential oil
      against oral pathogens.
AB  - INTRODUCTION: To assess the antibacterial effects of an Iranian endemic essential
      oil, Satureja Khuzistanica Jamzad (SKJ) when used as an intracanal antiseptic and
      interappointment medicament. MATERIALS AND METHODS: Antimicrobial activity and
      minimum inhibition concentrations (MICs) of SKJ essential oil with and without
      calcium hydroxide (CH) against eleven aerobic, microaerophilic and anaerobic
      bacteria were assessed. The evaluation was carried out by agar dilution and well
      diffusion methods. The results were measured and recorded by an independent
      observer. Data were analyzed statistically using student t-test. RESULTS: The MIC
      for eight species was recorded in 0.31 mg/mL of essential oil. Pseudomonas
      aeruginosa with a MIC value of 1.25 mg/mL appeared to be the most resistant
      bacterium; while only 0.16 mg/mL of essential oil was sufficient to inhibit the
      growth of Bacillus subtilis and Staphylococcus aureus. The inhibition zone of the
      antiseptic oil (at 0.31 mg/mL) with E. faecalis in the well diffusion method was
      13 mm; this was comparable with 12.5 mm inhibition zone value of the tetracycline
      disc (30 ug). No synergistic effect was found in combination of essential oil and
      CH powder. CONCLUSION: SKJ essential oil with the concentration of 0.31 mg/mL is
      effective against most of oral pathogens including E. faecalis.

PMID- 23864871
TI  - Coronal and apical sealing ability of a new endodontic cement.
AB  - INTRODUCTION: This in vitro study aims to evaluate the coronal and apical sealing
      ability of gutta-percha (GP) root filling used with either mineral trioxide
      aggregate (MTA), new endodontic cement (NEC) or AH26 as filler/sealers. MATERIALS
      AND METHODS: Forty eight single-rooted extracted teeth were selected, decoronated
      and then instrumented. Samples were randomly divided into three experimental
      (n=12) and two control groups (n=6). In group 1, root canals were filled using
      lateral condensation technique (L); while single cone technique (S) was used for
      groups 2 and 3. AH26, MTA and NEC were the root canal sealer/fillers in groups 1,
      2 and 3, respectively. Samples were immersed in 1% methylene-blue dye and then
      independently centrifuged apically and coronally. The roots were split
      longitudinally and linear extent of dye penetration was measured with a
      stereomicroscope from apical and coronal directions. Data were analyzed using One
      way ANOVA and T-test. RESULTS: No statistical differences in mean apical dye
      penetration between groups LGP/AH26, SGP/MTA and SGP/NEC were found; SGP/NEC
      group showed significantly less coronal dye penetration (P<0.001). CONCLUSION:
      Considering the limitations of this in vitro study, it was concluded that the
      simple single cone technique with NEC can provide favorable coronal and apical
      seal.

PMID- 23864872
TI  - Histologic effects of demineralized bone matrix on regeneration of alveolar
      socket in diabetic rats.
AB  - INTRODUCTION: The aim of this in vivo study was to determine the effect of
      demineralized bone matrix (DBM) on alveolar bone repair in type I diabetic rats.
      MATERIALS AND METHODS: This study was carried out on 40 adult (8 weeks-old)
      albino rats with an average weight of 200-250 grams. The animals were divided
      into four groups (n=10) as follows: group 1 nondiabetic rats, group 2, 3 and 4
      were diabetic rats, group 4 rats took one unit of insulin daily. Diabetes was
      induced by Alloxan Monohydrate through the tail veins of the rats in groups 2-4.
      Only group 4 received insulin NPH 1 unit daily. After 10 days, the upper right
      incisors of all samples were extracted and the socket was filled with DBM in
      groups 3 and 4. The animals were sacrificed at the end of week 1 and 2. The
      specimens were prepared and stained with H&E. RESULTS: Histological results of
      group 4 displayed osteoblastic activity and bone formation with collagen fibers
      at the end of the first week and thick bone trabeculae formation in vicinity of
      DBM at the end of second week. In group 3, DBM showed some osteoinductivity at
      the end of the first week, but in some regions DBM particles were degraded by
      osteoclastic activity. Bone trabeculae formed with a dispersed and separate
      pattern at the end of second week. In group 2 hematoma and inflammation were
      dominant histological features at the end of first and second weeks; poor bone
      formation was detected in these two groups (2 and 3). In group 1, the results
      were as expected. CONCLUSION: It seems demineralized bone matrix simulate
      osteoblastic activity.

PMID- 23864873
TI  - Connective Tissue Reaction to White and Gray MTA Mixed With Distilled Water or
      Chlorhexidine in Rats.
AB  - INTRODUCTION: The purpose of this study was to compare the histocompatibility of
      white (WMTA) and gray (GMTA) mineral trioxide aggregate mixed with 0.12%
      chlorhexidine (CHX) and distilled water (DW) in subcutaneous connective tissues
      of rats. MATERIALS AND METHODS: The freshly mixed WMTA and GMTA with CHX or DW
      were inserted in polyethylene tubes and implanted into dorsal subcutaneous
      connective tissue of 50 Wistar Albino rats; tissue biopsies were collected and
      were then examined histologically 7, 15, 30, 60 and 90 days after the
      implantation procedure. The histology results were scored from 1-4; score 4 was
      considered as the worst finding. Data were analyzed using one-way ANOVA tests.
      RESULTS: All experimented materials were tolerated well by the connective tissues
      after 90-day evaluation, except for the WMTA/CHX group that had significantly
      more mean inflammatory scores (P<0.001). There was a statistically significant
      difference in the mean inflammation grades between experimental groups in each
      interval (P<0.001). After 90 days, GMTA/CHX group had the lowest inflammatory
      score. CONCLUSION: Although adding CHX to WMTA produces significantly higher
      inflammatory response, it seems a suitable substitute for DW in combination with
      GMTA. Further research is necessary to recommend this mixture for clinical use.

PMID- 23864874
TI  - Evaluation of cytotoxicity of different root canal sealers and their effect on
      cytokine production.
AB  - INTRODUCTION: Endodontic sealers are in direct contact with periradicular tissues
      and play a critical role in regeneration and pathogenesis of periradicular
      diseases. The aim of this study was to compare cytotoxicity of four different
      types of sealers including AH plus, Sankin, Tubliseal EWT and Apexit as well as
      their effect on cytokine release of L929 fibroblasts. MATERIALS AND METHODS: In
      this experimental study, cells were cultured in Complete Medium Culture (CMC) and
      then divided into two test groups. In group 1, sealers were added to cell culture
      wells immediately after mixing. In group 2, sealers were added to cell cultures 3
      hours after mixing. Cell viability was evaluated by MTT assay after 4, 24 and 168
      hours. The amount of Interleukin-6 (IL-6) released in response to the sealers was
      also evaluated by ELISA technique on fibroblasts after 24 hour period. Data were
      analyzed using Kruskal-Wallis and Mann Whitey-U tests. RESULTS: Significant
      differences were seen in cytotoxicity in both groups (P<0.001). The least
      cytotoxic sealers were AH Plus and Sankin respectively, whereas Tubliseal EWT
      showed the greatest cytotoxicity. Production of IL-6 was significantly different
      among studied groups (P<0.001). The highest IL-6 level was observed in Tubliseal
      EWT and Sankin groups; which was statistically significant (P<0.001). CONCLUSION:
      AH plus has less cytotoxicity and induces less IL-6 release. Tubliseal EWT has
      greater cytotoxicity and induces more IL-6 release than other sealers. This
      should be considered during their routine use in root canal treatments.

PMID- 23864875
TI  - Endodontic Treatment of a Maxillary First Premolar with Type IV Buccal Root
      Canal: A Case Report.
AB  - The maxillary first premolar may present large number of anatomic variations. The
      clinician should be aware of the configuration of the pulp system. Maxillary
      first premolars usually have two canals. The incidence of three canals in these
      teeth is quite rare. This case report presents the diagnosis and clinical
      management of a maxillary first premolar with two distinct canals in the apical
      third of buccal root (type IV), drawing particular attention to tactile
      examination of all the canal walls. 

PMID- 23864876
TI  - Microglia and macrophages in malignant gliomas: recent discoveries and
      implications for promising therapies.
AB  - Malignant gliomas are the most common primary brain tumors. Their deadliest
      manifestation, glioblastoma multiforme (GBM), accounts for 15% of all primary
      brain tumors and is associated with a median survival of only 15 months even
      after multimodal therapy. There is substantial presence of microglia and
      macrophages within and surrounding brain tumors. These immune cells acquire an
      alternatively activated phenotype with potent tumor-tropic functions that
      contribute to glioma growth and invasion. In this review, we briefly summarize
      recent data that has been reported on the interaction of microglia/macrophages
      with brain tumors and discuss potential application of these findings to the
      development of future antiglioma therapies. 

PMID- 23864877
TI  - The correlations of disease activity, socioeconomic status, quality of life, and
      depression/anxiety in Chinese patients with systemic lupus erythematosus.
AB  - The prevalence of psychological problems is frequent in systemic lupus
      erythematosus (SLE) patients and appears to be increasing. The current study
      investigated the relationship among disease parameters, quality of life, and the
      psychological status in Chinese patients with SLE. A self-report survey design
      was administered to 170 SLE patients and 210 healthy individuals using the Self
      Rating Anxiety Scale, the Self-Rating Depression Scale, and the Short Form 36
      health survey (SF-36). Our results showed that 20.3% SLE patients had anxiety,
      and 32.9% had depression, which were significantly higher than the control group
      (7.1%, 14.3%, resp.). And there were significant correlations among socioeconomic
      status (SES), disease activity, and anxiety/depression in SLE patients.
      Meanwhile, SF-36 analysis results revealed that VT, PF, and RP scales were the
      most powerful predictors of anxiety of SLE patients, and SLEDAI, VT, PF, SF, and
      RE domains were significantly accounted for anxiety. In summary, there were
      significant relationships among disease parameters, quality of life, and
      anxiety/depression in Chinese SLE patients. Therefore, it is necessary to have
      psychiatric and psychological evaluations and formulate an integrated approach
      for managing mental health in Chinese lupus patients, especially those who have
      high disease activity, low SES, and poor quality of life. 

PMID- 23864878
TI  - Microglia play a major role in direct viral-induced demyelination.
AB  - Microglia are the resident macrophage-like populations in the central nervous
      system (CNS). Microglia remain quiescent, unable to perform effector and antigen
      presentation (APC) functions until activated by injury or infection, and have
      been suggested to represent the first line of defence for the CNS. Previous
      studies demonstrated that microglia can be persistently infected by neurotropic
      mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with
      subsequent axonal loss, and demyelination and serve as a virus-induced model of
      human neurological disease multiple sclerosis (MS). Current studies revealed that
      MHV infection is associated with the pronounced activation of microglia during
      acute inflammation, as evidenced by characteristic changes in cellular morphology
      and increased expression of microglia-specific proteins, Iba1 (ionized calcium
      binding adaptor molecule 1), which is a macrophage/microglia-specific novel
      calcium-binding protein and involved in membrane ruffling and phagocytosis.
      During chronic inflammation (day 30 postinfection), microglia were still present
      within areas of demyelination. Experiments performed in ex vivo spinal cord slice
      culture and in vitro neonatal microglial culture confirmed direct microglial
      infection. Our results suggest that MHV can directly infect and activate
      microglia during acute inflammation, which in turn during chronic inflammation
      stage causes phagocytosis of myelin sheath leading to chronic inflammatory
      demyelination. 

PMID- 23864879
TI  - Mucins help to avoid alloreactivity at the maternal fetal interface.
AB  - During gestation, many different mechanisms act to render the maternal immune
      system tolerant to semi-allogeneic trophoblast cells of foetal origin, including
      those mediated via mucins that are expressed during the peri-implantation period
      in the uterus. Tumour- associated glycoprotein-72 (TAG-72) enhances the already
      established tolerogenic features of decidual dendritic cells with the inability
      to progress towards Th1 immune orientation due to lowered interferon (IFN)- gamma
      and interleukin (IL)-15 expression. Mucine 1 (Muc 1) supports alternative
      activation of decidual macrophages, restricts the proliferation of decidual
      regulatory CD56(+) bright natural killer (NK) cells, and downregulates their
      cytotoxic potential, including cytotoxic mediator protein expression. Removing
      TAG-72 and Muc 1 from the eutopic implantation site likely contributes to better
      control of trophoblast invasion by T cells and NK cells and appears to have
      important immunologic advantages for successful implantation, in addition to
      mechanical advantages. However, these processes may lead to uncontrolled
      trophoblast growth after implantation, inefficient defence against infection or
      tumours, and elimination of unwanted immunocompetent cells at the maternal-foetal
      interface. The use of mucins by tumour cells to affect the local microenvironment
      in order to avoid the host immune response and to promote local tumour growth,
      invasion, and metastasis confirms this postulation. 

PMID- 23864880
TI  - Bone effects of biologic drugs in rheumatoid arthritis.
AB  - Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to
      reduce both disease activity and radiographic progression of joint disease. These
      drugs are directed against several proinflammatory cytokines (TNF alpha , IL-6,
      and IL-1) which are involved both in the pathogenesis of chronic inflammation and
      progression of joint structural damage and in systemic and local bone loss
      typically observed in RA. However, the role of biologic drugs in preventing bone
      loss in clinical practice has not yet clearly assessed. Many clinical studies
      showed a trend to a positive effect of biologic agents in preventing systemic
      bone loss observed in RA. Although the suppression of inflammation is the main
      goal in the treatment of RA and the anti-inflammatory effects of biologic drugs
      exert a positive effect on bone metabolism, the exact relationship between the
      prevention of bone loss and control of inflammation has not been clearly
      established, and if the available biologic drugs against TNF alpha , IL-1, and IL
      6 can exert their effect on systemic and local bone loss also through a direct
      mechanism on bone cell metabolism is still to be clearly defined. 

PMID- 23864881
TI  - Synergistic Anticancer Effects of Vorinostat and Epigallocatechin-3-Gallate
      against HuCC-T1 Human Cholangiocarcinoma Cells.
AB  - The aim of this study was to investigate the effect of the combination of
      vorinostat and epigallocatechin-3-gallate against HuCC-T1 human
      cholangiocarcinoma cells. A novel chemotherapy strategy is required as
      cholangiocarcinomas rarely respond to conventional chemotherapeutic agents. Both
      vorinostat and EGCG induce apoptosis and suppress invasion, migration, and
      angiogenesis of tumor cells. The combination of vorinostat and EGCG showed
      synergistic growth inhibitory effects and induced apoptosis in tumor cells. The
      Bax/Bcl-2 expression ratio and caspase-3 and -7 activity increased, but poly (ADP
      ribose) polymerase expression decreased when compared to treatment with each
      agent alone. Furthermore, invasion, matrix metalloproteinase (MMP) expression,
      and migration of tumor cells decreased following treatment with the vorinostat
      and EGCG combination compared to those of vorinostat or EGCG alone. Tube length
      and junction number of human umbilical vein endothelial cells (HUVECs) decreased
      as well as vascular endothelial growth factor expression following vorinostat and
      EGCG combined treatment. These results indicate that the combination of
      vorinostat and EGCG had a synergistic effect on inhibiting tumor cell
      angiogenesis potential. We suggest that the combination of vorinostat and EGCG is
      a novel option for cholangiocarcinoma chemotherapy. 

PMID- 23864882
TI  - The action of antidiabetic plants of the canadian james bay cree traditional
      pharmacopeia on key enzymes of hepatic glucose homeostasis.
AB  - We determined the capacity of putative antidiabetic plants used by the Eastern
      James Bay Cree (Canada) to modulate key enzymes of gluconeogenesis and glycogen
      synthesis and key regulating kinases. Glucose-6-phosphatase (G6Pase) and glycogen
      synthase (GS) activities were assessed in cultured hepatocytes treated with crude
      extracts of seventeen plant species. Phosphorylation of AMP-dependent protein
      kinase (AMPK), Akt, and Glycogen synthase kinase-3 (GSK-3) were probed by Western
      blot. Seven of the seventeen plant extracts significantly decreased G6Pase
      activity, Abies balsamea and Picea glauca, exerting an effect similar to insulin.
      This action involved both Akt and AMPK phosphorylation. On the other hand,
      several plant extracts activated GS, Larix laricina and A. balsamea, far
      exceeding the action of insulin. We also found a significant correlation between
      GS stimulation and GSK-3 phosphorylation induced by plant extract treatments. In
      summary, three Cree plants stand out for marked effects on hepatic glucose
      homeostasis. P. glauca affects glucose production whereas L. laricina rather acts
      on glucose storage. However, A. balsamea has the most promising profile,
      simultaneously and powerfully reducing G6Pase and stimulating GS. Our studies
      thus confirm that the reduction of hepatic glucose production likely contributes
      to the therapeutic potential of several antidiabetic Cree traditional medicines. 

PMID- 23864883
TI  - Integrative TCM Conservative Therapy for Low Back Pain due to Lumbar Disc
      Herniation: A Randomized Controlled Clinical Trial.
AB  - Low back pain due to lumbar disc herniation (LDH) is very common in clinic. This
      randomized controlled trial was designed to investigate the effects of
      integrative TCM conservative therapy for low back pain due to LDH. A total of 408
      patients with low back pain due to LDH were randomly assigned to an experimental
      group with integrative TCM therapy and a control group with normal conservative
      treatment by the ratio of 3 : 1. The primary outcome was the pain by the visual
      analogue scale (VAS). The secondary outcome was the low back functional
      activities by Chinese Short Form Oswestry Disability Index (C-SFODI). Immediately
      after treatment, patients in the experimental group experienced significant
      improvements in VAS and C-SFODI compared with the control group (between-group
      difference in mean change from baseline, -16.62 points, P < 0.001 in VAS; -15.55
      points, P < 0.001 in C-SFODI). The difference remained at one-month followup, but
      it is only significant in C-SFODI at six-month followup (-7.68 points, P <
      0.001). No serious adverse events were observed. These findings suggest that
      integrative TCM therapy may be a beneficial complementary and alternative therapy
      for patients with low back pain due to LDH. 

PMID- 23864885
TI  - The impacts of along-channel acupuncture on the protein expressions of the
      chloride channel of the rats with myocardial ischemia.
AB  - Recent evidence suggests that chloride (CL(-)) channels are involved in
      myocardial ischemia. In this study, the impact of acupuncture on the protein
      expressions of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and CLC
      2 CL(-) channel of the rats with myocardial ischemia were tested and its
      mechanism was explored. The rats for experiment were distributed randomly into 5
      groups: blank control group, modeling control group, Neiguan (PC-6) treatment
      group, Lieque (LU-7) control group, and Non-acupoint control group. The rats of
      all groups, except the blank control group, had myocardial ischemia via multiple
      subcutaneous injection of isoproterenol (ISO). Electroacupuncture treatment was
      given to Neiguan (PC-6) treatment group, Lieque (LU-7) control group, and Non
      acupoints control group, respectively, once a day for 7 days. The results show
      that acupuncture can alleviate the myocardial ischemia of cardiac tissue,
      decrease significantly the activities of serum SOD and MDA, and thereby influence
      the protein expressions of CFTR and CLC-2 in CL(-) channels. The results of the
      study implies that acupuncture suppresses the pathological changes of cardiac
      tissue of rats with myocardial ischemia and regulates the protein expression of
      CFTR and CLC-2 CL(-) channels, which may serve as one possible mechanism to
      reduce myocardial ischemia. 

PMID- 23864884
TI  - Characterization of deqi sensation and acupuncture effect.
AB  - Acupuncture stimulation elicits deqi, a composite of unique sensations. According
      to traditional Chinese medicine (TCM), deqi experienced by patients is often
      described as suan (aching or soreness), ma (numbness or tingling), zhang
      (fullness, distention, or pressure), and zhong (heaviness) and is felt by the
      acupuncturists (needle grasping) as tense, tight, and full. It is believed that
      deqi may be an important variable in the studies of the mechanism and efficacy of
      acupuncture treatment. In recent years, great efforts have been made to
      understand deqi, which include a couple of questionnaires to qualify and quantify
      deqi sensations, neuroimaging studies of deqi and acupuncture, physiological
      mechanisms of deqi, and the relation between deqi and clinical efficacy. However,
      many problems need to be resolved, and more researches are required to be made in
      the future. 

PMID- 23864886
TI  - Reconstitution of kidney side population cells after ischemia-reperfusion injury
      by self-proliferation and bone marrow-derived cell homing.
AB  - The aim of this study was to examine the contribution of side population (SP)
      cells from kidney and bone marrow for reconstitution of kidney SP pools after
      ischemia-reperfusion injury (IRI). The SP and non-SP cells in kidneys following
      IRI were isolated and serially assessed by fluorescence-activated cell sorting.
      The apoptosis, proliferation, phenotype, and paracrine actions of SP cells were
      evaluated in vitro and in vivo. Results indicated that the SP cells from ischemic
      kidney were acutely depleted within one day following renal IRI and were
      progressively restored to baseline within 7 days after IRI, through both
      proliferation of remaining kidney SP cells and homing of bone marrow-derived
      cells to ischemic kidney. Either hypoxia or serum deprivation alone increased
      apoptosis of SP cells, and a combination of both further aggravated it.
      Furthermore, hypoxia in vivo and in vitro induced the increase in the secretion
      of vascular endothelial growth factor, insulin-like growth factor 1, hepatocyte
      growth factor, and stromal cell-derived factor-1 alpha in kidney SP but not non
      SP cells. In summary, these results suggest that following renal IRI, kidney SP
      cells are acutely depleted and then progressively restored to baseline levels by
      both self-proliferation and extrarenal source, that is, bone marrow-derived cell
      homing. 

PMID- 23864887
TI  - Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ER alpha
      Inhibition.
AB  - The anthraquinones emodin and aloe-emodin are abundant in rhubarb. Several lines
      of evidence indicate that emodin and aloe-emodin have estrogenic activity as
      phytoestrogens. However, their effects on estrogen receptor alpha (ER alpha )
      activation and breast cancer cell growth remain controversial. The goal of this
      study is to investigate the effects and molecular mechanisms of emodin and aloe
      emodin on breast cancer cell proliferation. Our results indicate that both emodin
      and aloe-emodin are capable of inhibiting breast cancer cell proliferation by
      downregulating ER alpha protein levels, thereby suppressing ER alpha
      transcriptional activation. Furthermore, aloe-emodin treatment led to the
      dissociation of heat shock protein 90 (HSP90) and ER alpha and increased ER alpha
      ubiquitination. Although emodin had similar effects to aloe-emodin, it was not
      capable of promoting HSP90/ER alpha dissociation and ER alpha ubiquitination.
      Protein fractionation results suggest that aloe-emodin tended to induce cytosolic
      ER alpha degradation. Although emodin might induce cytosolic ER alpha
      degradation, it primarily affected nuclear ER alpha distribution similar to the
      action of estrogen when protein degradation was blocked. In conclusion, our data
      demonstrate that emodin and aloe-emodin specifically suppress breast cancer cell
      proliferation by targeting ER alpha protein stability through distinct
      mechanisms. These findings suggest a possible application of anthraquinones in
      preventing or treating breast cancer in the future. 

PMID- 23864888
TI  - Indian traditional ayurvedic system of medicine and nutritional supplementation.
AB  - Food is the major source for serving the nutritional needs, but with growing
      modernization some traditional ways are being given up. Affluence of working
      population with changing lifestyles and reducing affordability of sick care, in
      terms of time and money involved, are some of the forces that are presently
      driving people towards thinking about their wellness. There has been increased
      global interest in traditional medicine. Efforts to monitor and regulate
      traditional herbal medicine are underway. Ayurveda, the traditional Indian
      medicine, remains the most ancient yet living traditions. Although India has been
      successful in promoting its therapies with more research and science-based
      approach, it still needs more extensive research and evidence base. Increased
      side effects, lack of curative treatment for several chronic diseases, high cost
      of new drugs, microbial resistance and emerging, diseases are some reasons for
      renewed public interest in complementary and alternative medicines. Numerous
      nutraceutical combinations have entered the international market through
      exploration of ethnopharmacological claims made by different traditional
      practices. This review gives an overview of the Ayurvedic system of medicine and
      its role in translational medicine in order to overcome malnutrition and related
      disorders. 

PMID- 23864889
TI  - The Effect of Camellia sinensis on Wound Healing Potential in an Animal Model.
AB  - Camellia sinensis (tea) is reported to have health benefits, including the
      building of healthy skin. This study evaluated the effects of topical application
      of Camellia sinensis extract on the rate of wound closure and the histology of
      wound area. A uniform area of 2.00 cm in diameter was excised from the neck of
      adult male Sprague Dawley rats. The animals were topically treated with 0.2 mL of
      vehicle (CMC), Intrasite gel (positive control), or 200 and 400 mg/mL of extract.
      Wounds dressed with the extract and Intrasite gel healed significantly earlier
      than those with vehicle. Histological analysis of the wound area after 10 days
      showed that wounds dressed with the extract had less scar width when compared to
      the control. The tissue contained less inflammatory cells and more collagen and
      angiogenesis, compared to wounds dressed with vehicle. In this study, Camellia
      sinensis showed high potential in wound healing activity. 

PMID- 23864890
TI  - Therapeutic and radiosensitizing effects of armillaridin on human esophageal
      cancer cells.
AB  - Background. Armillaridin (AM) is isolated from Armillaria mellea. We examined the
      anticancer activity and radiosensitizing effect on human esophageal cancer cells.
      Methods. Human squamous cell carcinoma (CE81T/VGH and TE-2) and adenocarcinoma
      (BE-3 and SKGT-4) cell lines were cultured. The MTT assay was used for cell
      viability. The cell cycle was analyzed using propidium iodide staining.
      Mitochondrial transmembrane potential was measured by DiOC6(3) staining. The
      colony formation assay was performed for estimation of the radiation surviving
      fraction. Human CE81T/VGH xenografts were established for evaluation of
      therapeutic activity in vivo. Results. AM inhibited the viability of four human
      esophageal cancer cell lines with an estimated concentration of 50% inhibition
      (IC50) which was 3.4-6.9 MUM. AM induced a hypoploid cell population and
      morphological alterations typical of apoptosis in cells. This apoptosis induction
      was accompanied by a reduction of mitochondrial transmembrane potential. AM
      accumulated cell cycle at G2/M phase and enhanced the radiosensitivity in
      CE81T/VGH cells. In vivo, AM inhibited the growth of CE81T/VGH xenografts without
      significant impact on body weight and white blood cell counts. Conclusion.
      Armillaridin could inhibit growth and enhance radiosensitivity of human
      esophageal cancer cells. There might be potential to integrate AM with
      radiotherapy for esophageal cancer treatment. 

PMID- 23864891
TI  - Effective Components of Panax quinquefolius and Corydalis tuber Protect
      Myocardium through Attenuating Oxidative Stress and Endoplasmic Reticulum Stress.
AB  - Both oxidative stress and endoplasmic reticulum stress (ERS) have been implicated
      in carcinogenesis and neurological diseases, while there are few reports about
      the mechanisms of them in the progression of acute myocardial infarction (AMI).
      This study examined oxidative stress and ERS in a rat model of AMI and evaluated
      their role in therapy by metoprolol and effective components of Panax
      quinquefolius and Corydalis tuber (EPC). In the present study a rat model of AMI
      was established by ligation of the left anterior descending coronary artery.
      After oral administration of metoprolol or low-to-high doses of EPC for 2 weeks,
      serum malondialdehyde (MDA), superoxide dismutase (SOD), and 8-iso-prostaglandin
      F2 alpha (8-iso-PGF2 alpha ) were detected using enzyme-linked immunosorbent
      assay (ELISA). Quantitative real-time PCR and Western blotting were used to
      examine mRNA and protein expressions of the hallmarks of ERS-glucose-regulated
      protein-78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP).
      We confirmed that both metoprolol and moderate-to-high dose of EPC decreased 8
      iso-PGF2 alpha serum level and downregulated the mRNA and protein expressions of
      GRP78 and CHOP in myocardium, while EPC also increased SOD serum level. These
      results indicated that metoprolol and EPC protect the myocardium by attenuating
      oxidative stress and ERS induced by myocardial infarction, highlighting the ERS
      pathways as potential therapeutic targets for AMI. 

PMID- 23864892
TI  - Anthocyanins from Vitis coignetiae Pulliat Inhibit Cancer Invasion and Epithelial
      Mesenchymal Transition, but These Effects Can Be Attenuated by Tumor Necrosis
      Factor in Human Uterine Cervical Cancer HeLa Cells.
AB  - Recently we have demonstrated that anthocyanins from fruits of Vitis coignetiae
      Pulliat (AIMs) have anticancer effects. Here, we investigate the effects of AIMs
      on cell proliferation and invasion as well as epithelial-mesenchymal transition
      (EMT) which have been linked to cancer metastasis in human uterine cervical
      cancer HeLa cells. AIMs inhibited the invasion of HeLa cells in a dose-dependent
      manner. AIMs inhibited MMP-9 expression in a dose-dependent manner. AIMs
      inhibited the motility of HeLa cells in a wound healing test. AIMs still
      suppressed NF- kappa B activation induced by TNF. AIMs also inhibited EMT in HeLa
      cells. AIMs suppressed vimentin, N-cadherin, and beta-catenin expression and
      induced E-cadherin. AIMs also suppressed expression of beta-catenin and Snail,
      which was regulated by GSK-3. These effects of AIMs were also limited in the HeLa
      cells treated with TNF. In conclusion, this study indicates that AIMs have
      anticancer effects by suppressing NF- kappa B-regulated genes and EMT, which
      relates to suppression of I kappa B alpha phosphorylation and GSK-3 activity,
      respectively. However, the effects of AIMs were attenuated in the TNF-high
      condition. 

PMID- 23864893
TI  - Reishi Protein LZ-8 Induces FOXP3(+) Treg Expansion via a CD45-Dependent
      Signaling Pathway and Alleviates Acute Intestinal Inflammation in Mice.
AB  - LZ-8, an immunomodulatory protein isolated from Ganoderma lucidum (also known as
      Ling-Zhi or Reishi), has been shown to promote cell proliferation and IL-2
      production in T cells. In this study, we show that LZ-8 induces the expansion of
      both murine and human CD4(+) T cells into FOXP3(+) regulatory T (Treg) cells. LZ
      8 treatment was found to stimulate a 4-fold and a 10-fold expansion in the Treg
      populations of murine and human primary CD4(+) T cells, respectively. In
      addition, the expression of CTLA-4 and IL-10 was induced in LZ-8-treated CD4(+) T
      cells. Using neutralizing antibodies and gene-deficient T-cell lines, we also
      found that LZ-8 promotes Treg expansion through a CD45-mediated signaling pathway
      and that the CD18-dependent induction of IL-2 was involved in Treg formation and
      IL-10 production. The suppressive activity of LZ-8 was confirmed using a murine
      model of DSS-induced colitis; the disease was alleviated by the adoptive transfer
      of LZ-8-treated CD4(+) T cells. In conclusion, a new regulatory function for LZ-8
      was identified, and the molecular mechanisms underlying this function were
      elucidated. 

PMID- 23864894
TI  - Antiulcerogenic Activity of the Hydroalcoholic Extract of Leaves of Croton
      campestris A. St.-Hill in Rodents.
AB  - Croton campestris A. St.-Hill., popularly known as "velame do campo," is a
      species native to the savannah area of Northeast Brazil, which is used by
      traditional communities in folk medicine for variety of health problems,
      especially detoxification, inflammation, and gastritis. The hydroalcoholic
      extract of C. campestris leaves (HELCC) was assessed for its antiulcerogenic
      effect in gastric lesion models and effect on intestinal motility in mice, and
      possible mechanisms of action were examined. HELCC showed significant
      gastroprotective action in all models of gastric ulcer evaluated; the results
      suggest that this action probably involves the nitric oxide pathway. HELCC did
      not show alteration of intestinal motility in mice. It was also found that C.
      campestris represents a promising natural source with important biological
      potential, justifying some of its uses in folk medicine. 

PMID- 23864895
TI  - Prevalence and Correlates of Discomfort and Acceptability of Acupuncture among
      Outpatients in Chinese Acupuncture and Moxibustion Departments: A Cross-Sectional
      Study.
AB  - Objective. This study aims to give a profile of discomfort and acceptability of
      acupuncture, including the prevalence and association with demographic and
      acupuncture-related factors. Methods. A cross-sectional study was conducted in
      Beijing, China. Outpatients of acupuncture and moxibustion departments were
      recruited using purposive sampling. 925 subjects were interviewed with an
      anonymous questionnaire. Multinomial and binary logistic regression were used to
      analyze factors affecting discomfort and acceptability of acupuncture. Results.
      The average VAS value of 925 subjects' acupuncture discomfort was 2.66 +/- 2.02,
      within the range of mild discomfort. Acupuncture was easily accepted by 81.1% of
      the subjects. Results of logistic regression were as follows: (1) subjects with a
      better knowledge of acupuncture, or a greater fear of pain or needles,
      experienced more "moderate to severe discomfort" and showed a decreased
      acupuncture acceptance (P < 0.001 or P < 0.01); (2) Acupuncture with less
      discomfort or implemented by a more qualified doctor was easy to be accepted (P <
      0.001); (3) subjects aged 20-29 preferred to report "moderate to severe
      discomfort" while those aged 40-59 preferred to report "slight discomfort" (P <
      0.001). Conclusion. Acupuncture is an acceptable therapy with less discomfort,
      which can be greatly affected by fear of pain or needles, age, knowledge of
      acupuncture, and professional title of acupuncturist. 

PMID- 23864896
TI  - Baicalein, Ethyl Acetate, and Chloroform Extracts of Scutellaria baicalensis
      Inhibit the Neuraminidase Activity of Pandemic 2009 H1N1 and Seasonal Influenza A
      Viruses.
AB  - This study rated antiviral activity of Scutellaria baicalensis Georgi (S.
      baicalensis) extracts against influenza A virus subtypes, for example, pandemic
      2009 H1N1, seasonal H1N1 and H3N2. Ethyl acetate (EtOAc) and chloroform extracts
      inhibited in vitro neuraminidase (NA) enzymatic activity and viral replication
      more than methanol (MeOH) extract. EtOAc extract demonstrated NA inhibition IC50
      values ranging from 73.16 to 487.40 MUg/mL and plaque reduction IC50 values
      ranging from 23.7 to 27.4 MUg/mL. Chloroform extract showed antiviral activities
      with plaque reduction IC50 values ranging from 14.16 to 41.49 MUg/mL Time-of
      addition assay indicated that EtOAc and chloroform extracts also significantly
      inhibited virus yields after infection. HPLC analysis demonstrated that baicalin
      was dominant in the MeOH extract; baicalein and chrysin were rich in the EtOAc
      and chloroform extracts. Molecular simulation revealed baicalein hydrogen bonding
      with Glu277 as well as hydrophobic and Van der Waals interactions with Ile222,
      Arg224, Ser246, and Tyr347 in NA1 active sites of NA1. Baicalein inhibited in
      vitro replication of influenza A viruses pandemic 2009 H1N1 (IC50 = 0.018 MUM)
      and seasonal 2007 H1N1 using plaque reduction assays. A combination of low-dose
      baicalein with other anti-influenza agents could be applicable for development of
      alternative remedies treating influenza A virus infection. 

PMID- 23864897
TI  - Trans- beta -Caryophyllene: An Effective Antileishmanial Compound Found in
      Commercial Copaiba Oil (Copaifera spp.).
AB  - This study investigated the leishmanicidal activity against Leishmania
      amazonensis of four commercial oils from Copaifera spp. named as C1, C2, C3, and
      C4, the sesquiterpene and diterpene pools obtained from distilling C4, and
      isolated beta -caryophyllene (CAR). Copaiba oils chemical compositions were
      analyzed by gas chromatography and correlated with biological activities.
      Diterpenes-rich oils C2 and C3 showed antipromastigote activity. Sesquiterpenes
      rich C1 and C4, and isolated CAR presented a dose-dependent activity against
      intracellular amastigotes, with IC50s of 2.9  u g/mL, 2.3  u g/mL, and 1.3  u
      g/mL (6.4  u M), respectively. Based on the highest antiamastigote activity and
      the low toxicity to the host cells, C4 was steamdistillated to separate pools of
      sesquiterpenes and diterpenes. Both pools were less active against L. amazonensis
      and more toxic for the macrophages than the whole C4 oil. The leishmanicidal
      activity of C3 and C4 oils, as well as C4 fractions and CAR, appears to be
      independent of nitric oxide production by macrophages. This study pointed out
      beta -caryophyllene as an effective antileishmanial compound and also to its role
      as potential chemical marker in copaiba oils or fractions derived thereof, aiming
      further development of this rainforest raw material for leishmaniasis therapy. 

PMID- 23864898
TI  - Oral administration of alkylglycerols differentially modulates high-fat diet
      induced obesity and insulin resistance in mice.
AB  - Alkylglycerols (AKGs) from shark liver oil (SLO) were demonstrated to have strong
      potency to stimulate immune response. However, no study has been conducted on the
      effects of AKGs on diet-induced obesity and metabolic inflammatory disorder. The
      purpose of the present study was to investigate the effect of two AKGs isoforms
      on obesity and insulin resistance in mice fed high-fat (HF) diet. Forty-eight
      C57BL/6 mice were divided into normal, HF, HF + 20 mg/kg selachyl alcohol (SA),
      HF + 200 mg/kg SA, HF + 20 mg/kg batyl alcohol (BA), and HF + 200 mg/kg BA
      groups. Body weight, fasting glucose, lipids, insulin and leptin levels, serum IL
      1beta, and TNF- alpha levels were compared among different groups. Our results
      showed that high-dose SA decreased body weight, serum triglyceride, cholesterol,
      fasting glucose level, insulin level, and serum leptin level of the HF fed mice,
      while high-dose BA increased fasting insulin level of the HF fed mice.
      Pretreatment of primary adipocytes with 10  MU M SA or BA differentially
      modulates LPS-mediated MAPK and NF- kappa B signaling. Our study demonstrated
      that oral administration of AKGs has differential effects on HF-induced obesity
      and metabolic inflammatory disorder in mice. 

PMID- 23864899
TI  - Antiadipogenic Effects of Aster glehni Extract: In Vivo and In Vitro Effects.
AB  - Aster glehni (AG) is a Korean traditional herb that grows in Ulleungdo Island,
      Republic of Korea. None of the several reports on AG include a determination of
      the effect of AG on adipogenesis. The primary aim of this study was to determine
      whether AG attenuates adipogenesis in mouse 3T3-L1 cells and epididymal fat
      tissue. AG blocked the differentiation of 3T3-L1 preadipocytes in a concentration
      dependent manner and suppressed the expression of adipogenesis-related genes such
      as PPAR gamma , C/EBP alpha , and SREBP1c, the master regulators of adipogenesis.
      Male C57BL/6J mice were divided randomly and equally into 4 diet groups: control
      diet (CON), high-fat diet (HFD), HFD with 1% AG extract added (AG1), and HFD with
      5% AG extract added (AG5). The experimental animals were fed HFD and the 2
      combinations for 10 weeks. Mice fed HFD with AG gained less body weight and
      visceral fat-pad weight than did the mice fed HFD alone. Moreover, AG inhibited
      the expression of important adipogenic genes such as PPAR gamma , C/EBP alpha ,
      SREBP1c, LXR, and leptin in the epididymal adipose tissue of the mice treated
      with AG1 and AG5. These findings indicate antiadipogenic and antiobesity effects
      of AG and suggest its therapeutic potential in obesity and obesity-related
      diseases. 

PMID- 23864900
TI  - Hemiparesis after Operation of Astrocytoma Grade II in Adults: Effects of
      Acupuncture on Sensory-Motor Behavior and Quality of Life.
AB  - To evaluate the effect of acupuncture on hemiparesis and quality of life for
      adults with brain astrocytoma grade II, we conducted a randomized, observer
      blinded clinical trial. Fifty-eight patients were randomized to standard
      rehabilitation (SR) therapy without acupuncture (n = 20), SR plus standard
      acupuncture (SA) (n = 19), and SR plus individualized acupuncture (IA) (n = 19).
      SA points were PC6, SP6, HT1, LU5, BL40, and ST36, while a special concept called
      "connecting and regulation Ren and Du" and "Jin-3-needling" served as IA. This
      treatment was individualized according to the clinical syndrome. The outcome was
      measured by the Barthel Index (BI), the Fugl-Meyer scale (FM), and the EORTC Core
      Quality of Life Questionnaire (QLQ-C30) with the Brain Cancer Module (BCM20). IA
      + SR reached significantly higher BI scores than SA + SR, which reached
      significantly higher BI scores than SR. IA + SR was significantly superior to SA
      + SR and to SR at the 8th week for the scores of FM motor and sensory assessments
      and most QLQ-C30-BCM20 items. In conclusion, the individualized acupuncture
      concept of "connecting and regulating Ren and Du" combined with "Jin-3-needling"
      offers a promising possibility for the treatment of hemiparesis due to
      astrocytoma, but further evaluation is mandatory. 

PMID- 23864901
TI  - Monoester-Diterpene Aconitum Alkaloid Metabolism in Human Liver Microsomes:
      Predominant Role of CYP3A4 and CYP3A5.
AB  - Aconitum, widely used to treat rheumatoid arthritis for thousands of years, is a
      toxic herb that can frequently cause fatal cardiac poisoning. Aconitum toxicity
      could be decreased by properly hydrolyzing diester-diterpene alkaloids into
      monoester-diterpene alkaloids. Monoester-diterpene alkaloids, including
      benzoylaconine (BAC), benzoylmesaconine (BMA), and benzoylhypaconine (BHA), are
      the primary active and toxic constituents of processed Aconitum. Cytochrome P450
      (CYP) enzymes protect the human body by functioning as the defense line that
      limits the invasion of toxicants. Our purposes were to identify the CYP
      metabolites of BAC, BMA, and BHA in human liver microsomes and to distinguish
      which isozymes are responsible for their metabolism through the use of chemical
      inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzyme. High-resolution
      mass spectrometry was used to characterize the metabolites. A total of 7, 8, and
      9 metabolites were detected for BAC, BMA, and BHA, respectively. The main
      metabolic pathways were demethylation, dehydrogenation, demethylation
      dehydrogenation, hydroxylation and didemethylation, which produced less toxic
      metabolites by decomposing the group responsible for the toxicity of the parent
      compound. Taken together, the results of the chemical inhibitors, monoclonal
      antibodies, and cDNA-expressed CYP enzymes experiments demonstrated that CYP3A4
      and CYP3A5 have essential functions in the metabolism of BAC, BMA, and BHA. 

PMID- 23864902
TI  - Whole-systems research in integrative inpatient treatment.

PMID- 23864903
TI  - The beginnings of modern research on propolis in poland.
AB  - Propolis studies in Poland were initiated by Professor Stan Scheller in the
      1960s. It was a team of Polish researchers who developed a method of introducing
      hydrophobic ethanol extracts of propolis (EEP) into aqueous solutions, which
      enabled the study of their biological properties. The studies performed in Poland
      showed that EEP possesses antioxidant, radioprotective, and immunostimulating
      properties. It was possible to demonstrate antibacterial activity of propolis on
      Gram-positive bacteria, virulent Mycobacterium tuberculosis, and protozoa as well
      as stimulating activity of aqueous extracts of propolis on proliferation of cells
      in vitro. Polish investigators showed that propolis stimulates regeneration of
      tissue, acts as antioxidant and radioprotector, has strong immunostimulative
      properties, affects animals' life span by extending it, and improves intellectual
      and life functions of the elderly. 

PMID- 23864904
TI  - Characterization of suicidal behaviour with self-organizing maps.
AB  - The study of the variables involved in suicidal behavior is important from a
      social, medical, and economical point of view. Given the high number of potential
      variables of interest, a large population of subjects must be analysed in order
      to get conclusive results. In this paper, we describe a method based on self
      organizing maps (SOMs) for finding the most relevant variables even when their
      relation to suicidal behavior is strongly nonlinear. We have applied the method
      to a cohort with more than 8,000 subjects and 600 variables and discovered four
      groups of variables involved in suicidal behavior. According to the results,
      there are four main groups of risk factors that characterize the population of
      suicide attempters: mental disorders, alcoholism, impulsivity, and childhood
      abuse. The identification of specific subpopulations of suicide attempters is
      consistent with current medical knowledge and may provide a new avenue of
      research to improve the management of suicidal cases. 

PMID- 23864905
TI  - Multiscale cross-approximate entropy analysis as a measure of complexity among
      the aged and diabetic.
AB  - Complex fluctuations within physiological signals can be used to evaluate the
      health of the human body. This study recruited four groups of subjects: young
      healthy subjects (Group 1, n = 32), healthy upper middle-aged subjects (Group 2,
      n = 36), subjects with well-controlled type 2 diabetes (Group 3, n = 31), and
      subjects with poorly controlled type 2 diabetes (Group 4, n = 24). Data
      acquisition for each participant lasted 30 minutes. We obtained data related to
      consecutive time series with R-R interval (RRI) and pulse transit time (PTT).
      Using multiscale cross-approximate entropy (MCE), we quantified the complexity
      between the two series and thereby differentiated the influence of age and
      diabetes on the complexity of physiological signals. This study used MCE in the
      quantification of complexity between RRI and PTT time series. We observed changes
      in the influences of age and disease on the coupling effects between the heart
      and blood vessels in the cardiovascular system, which reduced the complexity
      between RRI and PTT series. 

PMID- 23864906
TI  - CFD modelling of abdominal aortic aneurysm on hemodynamic loads using a realistic
      geometry with CT.
AB  - The objective of this study is to find a correlation between the abdominal aortic
      aneurysm (AAA) geometric parameters, wall stress shear (WSS), abdominal flow
      patterns, intraluminal thrombus (ILT), and AAA arterial wall rupture using
      computational fluid dynamics (CFD). Real AAA 3D models were created by three
      dimensional (3D) reconstruction of in vivo acquired computed tomography (CT)
      images from 5 patients. Based on 3D AAA models, high quality volume meshes were
      created using an optimal tetrahedral aspect ratio for the whole domain. In order
      to quantify the WSS and the recirculation inside the AAA, a 3D CFD using finite
      elements analysis was used. The CFD computation was performed assuming that the
      arterial wall is rigid and the blood is considered a homogeneous Newtonian fluid
      with a density of 1050 kg/m(3) and a kinematic viscosity of 4 * 10(-3) Pa.s.
      Parallelization procedures were used in order to increase the performance of the
      CFD calculations. A relation between AAA geometric parameters (asymmetry index (
      beta ), saccular index ( gamma ), deformation diameter ratio ( chi ), and
      tortuosity index ( epsilon )) and hemodynamic loads was observed, and it could be
      used as a potential predictor of AAA arterial wall rupture and potential ILT
      formation. 

PMID- 23864907
TI  - Social Epigenetics and Equality of Opportunity.
AB  - Recent epidemiological reports of associations between socioeconomic status and
      epigenetic markers that predict vulnerability to diseases are bringing to light
      substantial biological effects of social inequalities. Here, we start the
      discussion of the moral consequences of these findings. We firstly highlight
      their explanatory importance in the context of the research program on the
      Developmental Origins of Health and Disease (DOHaD) and the social determinants
      of health. In the second section, we review some theories of the moral status of
      health inequalities. Rather than a complete outline of the debate, we single out
      those theories that rest on the principle of equality of opportunity and analyze
      the consequences of DOHaD and epigenetics for these particular conceptions of
      justice. We argue that DOHaD and epigenetics reshape the conceptual distinction
      between natural and acquired traits on which these theories rely and might
      provide important policy tools to tackle unjust distributions of health.

PMID- 23864908
TI  - Ancillary Care: From Theory to Practice in International Clinical Research.
AB  - How international research might contribute to justice in global health has not
      been substantively addressed by bioethics. This article describes how the
      provision of ancillary care can link international clinical research to the
      reduction of global health disparities. It identifies the ancillary care
      obligations supported by a theory of global justice, showing that Jennifer
      Ruger's health capability paradigm requires the delivery of ancillary care to
      trial participants for a limited subset of conditions that cause severe morbidity
      and mortality. Empirical research on the Shoklo Malaria Research Unit's (SMRU)
      vivax malaria treatment trial was then undertaken to demonstrate whether and how
      these obligations might be upheld in a resource-poor setting. Our findings show
      that fulfilment of the ancillary care obligations is feasible where there is
      commitment from chief investigators and funders and is strongly facilitated by
      SMRU's dual role as a research unit and medical non-governmental organization.

PMID- 23864909
TI  - Enhancing Children against Unhealthy Behaviors-An Ethical and Policy Assessment
      of Using a Nicotine Vaccine.
AB  - Health behaviors such as tobacco use contribute significantly to poor health. It
      is widely recognized that efforts to prevent poor health outcomes should begin in
      early childhood. Biomedical enhancements, such as a nicotine vaccine, are now
      emerging and have potential to be used for primary prevention of common diseases.
      In anticipation of such enhancements, it is important that we begin to consider
      the ethical and policy appropriateness of their use with children. The main
      ethical concerns raised by enhancing children relate to their impact on
      children's well-being and autonomy. These concerns are significant, however they
      do not appear to apply in the case of the nicotine vaccine; indeed the vaccine
      could even further these goals for children. Nevertheless, concerns about broadly
      applying this enhancement may be more challenging. The vaccine may be less cost
      effective than alternative public efforts to prevent tobacco use, utilizing it
      could distract from addressing the foundational causes of smoking and it might
      not be publically acceptable. Empirical research about these concerns is needed
      to ascertain their likelihood and impact as well as how they could be minimized.
      This research could help determine whether behavior-related enhancements hold
      promise for improving children's health.

PMID- 23864910
TI  - Proteolytic Cleavage of the Red Blood Cell Glycocalyx in a Genetic Form of
      Hypertension.
AB  - Recent evidence suggests that the spontaneously hypertensive rat (SHR) has an
      elevated level of proteases, including matrix metalloproteinases (MMPs), involved
      in cell membrane receptor cleavage. We hypothesize that SHR red blood cells
      (RBCs) may be subject to an enhanced glycocalyx cleavage compared to the RBCs of
      the normotensive Wistar-Kyoto (WKY) rats. By direct observation of RBC rouleaux,
      we found no significant difference in RBC aggregation for unseparated SHR and WKY
      RBCs. However, lighter SHR RBCs have a greater tendency to aggregate than WKY
      RBCs when separated by centrifugation. When SHR plasma was mixed with WKY RBCs,
      SHR plasma proteases cleaved the glycocalyx of WKY RBCs, a process that can be
      blocked by MMP inhibition. When treated with MMPs, WKY RBCs showed strong
      aggregation in dextran but not in fibrinogen, indicating that RBC membrane
      glycoproteins from the inner core of the glycocalyx were cleaved and that dextran
      was able to bind to the lipid portion of the RBC membrane. In contrast, treatment
      with amylases produced fibrinogen-induced aggregation with fibrinogen binding to
      the protein core. MMP cleavage of RBC glycocalyx reduces RBC adhesion to
      macrophages as a mechanism to remove old RBCs from the circulation.

PMID- 23864911
TI  - Current treatment of low grade gliomas.
AB  - Low grade gliomas affect predominantly young adults, and have a relatively
      favorable prognosis compared to grade III and grade IV gliomas. The challenge for
      an optimal management of these patients is to find the balance between an optimal
      survival and the preservation of neurological function including cognition.
      Because all medical treatments may induce side effects, in young and nearly
      asymptomatic patients the choices can be difficult. This review summarizes the
      current strategies: a watch-and-wait policy, surgery, chemotherapy, and
      radiotherapy.

PMID- 23864912
TI  - Update on molecular and genetic alterations in adult medulloblastoma.
AB  - Medulloblastoma encompasses a group of aggressively growing cancers that arise
      either in the cerebellum or brain stem. They present primarily in children, with
      80-85 % of medulloblastomas being diagnosed in patients of 16 years and younger.
      In adults, medulloblastomas are rare and account for less than 1 % of
      intracranial malignancies. Due to the low incidence of medulloblastoma in adults,
      the biology and genetics of adult medulloblastomas have long been poorly
      understood. Many centers therefore still treat adults either by radiotherapy only
      or by using glioblastoma protocols (both often noncurative), or with standard
      pediatric medulloblastoma regimes (often associated with dose-limiting
      toxicity).Current clinical staging systems discriminate between standard-risk or
      high-risk patients based on clinical and histological parameters. However,
      clinico-pathological features often fail to accurately predict treatment
      response. In children, molecularly defined risk assessment has become important
      to improve survival of high-risk patients and to decrease treatment-related
      toxicity and long-term sequelae in standard-risk patients. However, several
      recent studies have shown that adult and pediatric medulloblastomas are
      genetically distinct and may require different algorithms for molecular risk
      stratification. Moreover, four subtypes of medulloblastoma have been identified
      that appear at different frequencies in children and adults and that have a
      different prognostic impact depending on age. Molecular markers such as
      chromosome 10q and chromosome 17 statuses can be used for molecular risk
      stratification of adult medulloblastoma, but only in a subgroup-specific context.
      Here we present an overview of the current knowledge of the genomics of adult
      medulloblastoma and how these tumors differ from their pediatric counterparts.

PMID- 23864914
TI  - The Prostate Cancer Intervention Versus Observation Trial (PIVOT) in Perspective.
AB  - Low risk localised prostate cancer may be able to be observed rather than treated
      according to the Prostate Cancer Intervention Versus Observation Trial (PIVOT).
      This review summarises the key issues surrounding the debate in the management of
      localised prostate cancer, and contextualises the PIVOT's contribution. 

PMID- 23864913
TI  - The quest for arterial recanalization in acute ischemic stroke-the past, present
      and the future.
AB  - Ischemic stroke is one of the major causes of mortality and long-term disability.
      In the recent past, only very few treatment options were available and a
      considerable proportion of stroke survivors remained permanently disabled.
      However, over the last 2 decades rapid advances in acute stroke care have
      resulted in a corresponding improvement in mortality rates and functional
      outcomes. In this review, we describe the evolution of systemic thrombolytic
      agents and various interventional devices, their current status as well as some
      of the future prospects. We reviewed literature pertaining to acute ischemic
      stroke reperfusion treatment. We explored the current accepted treatment
      strategies to attain cerebral reperfusion via intravenous modalities and compare
      and contrast them within the boundaries of their clinical trials. Subsequently we
      reviewed the trials for interventional devices for acute ischemic stroke,
      categorizing them into thrombectomy devices, aspiration devices, clot disruption
      devices and thrombus entrapment devices. Finally we surveyed several of the
      alternative reperfusion strategies available. We also shed some light on the
      controversies surrounding the current strategies of treatment of acute ischemic
      stroke. Acute invasive interventional strategies continue to improve along with
      the noninvasive modalities. Both approaches appear promising. We conducted a
      comprehensive chronological review of the existing treatments as well as upcoming
      remedies for acute ischemic stroke. 

PMID- 23864915
TI  - Biochemical pregnancy during assisted conception: a little bit pregnant.
AB  - Assisted reproductive technology (ART) has revolutionized the management of
      subfertility as many couples who previously had no hope of achieving a pregnancy
      are able to do so. Several factors contribute to the successful outcome of
      assisted conception. The period of waiting for the pregnancy test after assisted
      conception could be very crucial to the patient. One outcome of assisted
      conception could be a positive pregnancy test which could lead to a clinical
      pregnancy resulting in a live birth, clinical pregnancy resulting in a
      miscarriage or a biochemical pregnancy. A negative pregnancy test, failure to
      fertilise and failure to respond to stimulation usually lead to a big blow to the
      couple. As far as biochemical pregnancy is concerned, its exact aetiology remains
      unknown. There are no definite predictive factors for its occurrence that can be
      remedied in subsequent cycles. Several associated aetiologies have been suggested
      in the literature. This review aims at addressing the issue of biochemical
      pregnancy after assisted conception as a prelude to conducting further studies to
      assess if there are any predictive factors for its occurrence. 

PMID- 23864916
TI  - Ezetimibe in combination with a statin does not reduce all-cause mortality.
AB  - BACKGROUND: Although the ezetimibe-statin combination has been shown to reduce
      LDL cholesterol by 12% compared to a statin alone, its effect on hard clinical
      endpoints such as mortality is less certain. Prior trials evaluated this
      combination in highly select population groups, but impact on all- cause
      mortality in the general population has not been reported. METHODS: A total of
      3,827 subjects who were prescribed either a statin (group 1) or the combination
      of statin with ezetimibe (group 2) between January 1st, 2005 and January 1st,
      2008 were studied. Socio-demographic and clinical variables and mortality records
      were analyzed. Univariate and stepwise multivariate logistic regression analysis
      was performed to identify the impact of ezetimibe on all-cause mortality,
      controlling for patient characteristics, selected cardiovascular diseases and
      risk factors, and medications. RESULTS: Group 1 (n = 2,909), and group 2 (n =
      918) were similar in regards to most demographic variables, 152 patients died
      from any cause during the study period. There was no difference in all cause
      mortality between the groups. Hypertension, higher HDL-C and omega-3 fatty acid
      use were associated with ezetimibe use in this cohort of patients and were
      considered as covariates in the analysis. Patients on the drug combination did
      not experience lower mortality after controlling for covariates and other
      significant risk factors. CONCLUSIONS: No significant mortality benefit was found
      with the use of ezetimibe in combination with a statin over use of a statin
      alone. Omega-3 fatty acid use and higher HDL-C demonstrated a substantial
      survival benefit.

PMID- 23864917
TI  - Comparing efficacy between regimens in the initial treatment of autoimmune
      hepatitis.
AB  - BACKGROUND: Autoimmune hepatitis is a chronic syndrome characterized by auto
      immunologic features generally including the presence of circulating auto
      antibodies and high serum globulin concentrations. The American Association for
      the Study of Liver Diseases (AASLD) recommends initial treatment or induction
      therapy for autoimmune hepatitis to involve a glucocorticoid alone or a
      combination of a glucocorticoid and an immunosuppressant. The objective of this
      study is to review and compare the efficacy of the treatment regimens described
      above among patients diagnosed with and treated for autoimmune hepatitis over the
      past 10 years in our center which is a major university based hospital. METHODS:
      We retrospectively identified patients above the age of 18 years diagnosed with
      autoimmune hepatitis in our center between February, 2003 and February, 2013
      using the ICD-9 code 571.42. The primary outcome of our study was efficacy of the
      treatment regimen. We defined efficacy by considering 3 scenarios: Complete
      Resolution, Incomplete Resolution and Treatment Failure. RESULTS: We found
      differences among 3 treatment groups: patients who received Prednisone and
      immunosuppressant from the beginning of their treatment course, patients who had
      an immunosuppressant introduced after about 4 weeks on Prednisone and patients
      who were placed on Prednisone alone. CONCLUSION: From our study, better efficacy
      was achieved in the induction phase using a combination of Prednisone and
      Azathioprine from the beginning of the treatment course.

PMID- 23864918
TI  - An Observational Retrospective Study Provide Information on Hospitalization and
      Severe Outcomes of the 2009 A(H1N1) Infection in Italy.
AB  - BACKGROUND: The aim of this study was to try to ascertain whether, in the absence
      of a pre-organized programme, locally collected data might provide information
      about the epidemiological and clinical characteristics of the recent A(H1N1)
      pandemic in Italy. METHODS: The study was an observational retrospective analysis
      of the clinic-epidemiological features performed by reviewing medical charts from
      141 hospitalized patients with laboratory confirmed pandemic A(H1N1) infection in
      Umbria, a region of central Italy, in the period July 2009 to March 2010.
      RESULTS: The pandemic virus was found capable of inducing severe illness
      requiring hospitalization or intensive care unit admission (ICU), or resulting in
      death. Age and comorbidity were found to be potential risk factors for severe
      disease. The mean age of the hospitalized patients was 37 years (range 0 - 93
      yrs), however the mean age of ICU admitted patients, including people who did not
      survive, was higher as compared with those admitted to general medical ward (54
      vs 35 yrs). The highest incidence of hospitalization was observed in the youngest
      group (0 - 17 yrs), the greatest rate of ICU admission in adults (18 - 64 years),
      and the risk of death in the oldest population (>= 65 yrs). Comorbity conditions
      were present in some (55%), but not all hospitalized patients and increased with
      the age and the severity of the illness. CONCLUSIONS: The data obtained are
      compatible with the identified epidemiological characteristics of the A(H1N1)
      pandemic derived from partial information previously collected in Italy and from
      studies conducted in other European and non European countries. The results of
      our retrospective observational study suggest that locally organized data
      collection may give information on the epidemiological and clinical
      characteristics of a pandemic that are compatible with those obtained from more
      complex and complete studies.

PMID- 23864919
TI  - C-reactive protein is not correlated with endothelial dysfunction in overweight
      and obese women.
AB  - BACKGROUND: Obesity is a complex and multifactorial disease, has an inflammatory
      pattern and is associated with higher cardiometabolic risk. There are recent
      reports associating an elevated C-Reactive Protein (CRP) with a microscopic
      endothelial dysfunction. The objective is to evaluate if there is an association
      between serum levels of CRP and endothelial function in women with
      overweight/obesity, as well as the correlation between CRP and anthropometric
      variables. METHODS: This is a cross-sectional study that analyzed secondary data
      from patients treated in an institution of tertiary education, as part of the
      weight excess and cardiometabolic disease survey. The study included patients
      with overweight/obesity who had CRP and endothelial function tests already made
      and inserted into the survey database. The endothelial function was evaluated by:
      reactive hyperemia test (endothelium-dependent vasodilation). All tests were
      recorded and later analyzed by the same echocardiographer who performed the
      examination. Statistical analyses were realized in the Statistical Package for
      the Social Sciences (SPSS) version 14. It was considered statistically
      significant a P value < 0.05. RESULTS: This study included 47, nonsmoker women.
      with a BMI of 32.37 +/- 5.06 kg/m(2), median of CRP of 2.59 mg/L and flow
      mediated dilation (FMD) of 8.75% +/- 5.22%. There was no correlation between CRP
      and endothelial dysfunction in this population (rs = 0.08, P = 0.64). No
      correlation was observed between CRP and BMI. There were no differences of
      endothelial dysfunction variables and CRP in groups in use or not of medications
      (Hypolipidemic, antihypertensives and hypoglycemic agents). CONCLUSION: There was
      no association between CRP and FMD and this can suggest that it is possible that
      the level of eNOS dysfunction associated with increased CRP is not enough to lead
      to macroscopic changes and harm vasodilation.

PMID- 23864920
TI  - Comparative approach to non-traumatic acute abdominal pain between elderly and
      non-elderly in the emergency department: a study in rural Greece.
AB  - BACKGROUND: Acute abdominal pain is one of the most common symptoms that
      emergency department physicians encounter during their practice. The difficult
      task of early diagnosis and management of abdominal pain becomes more complicated
      when it involves elderly patients. The aim of this study was to evaluate the
      presence of age based differences regarding the management of acute non-traumatic
      abdominal pain in the Emergency Department. METHODS: We retrospectively analyzed
      the medical records of 933 patients with acute non-traumatic abdominal pain in
      the emergency department of a regional hospital during one year period. RESULTS:
      There were no differences between native and foreign elder patients regarding the
      use of imaging studies and discharge status. Although no differences were
      detected regarding the clinical presentation and management within the Emergency
      Department, elder patients with abdominal pain had a higher likelihood of being
      admitted for further hospitalization and were more often submitted to diagnostic
      examinations. The elder group had a trend towards lower number of cases of non
      specific abdominal pain in comparison with the non-elders. Between male and
      female elders no statistically significant differences were detected.
      CONCLUSIONS: A thorough work-up is essential for all patients. The clinician
      should always be alerted, since elderly patients may require more tests and they
      should have a low threshold for hospital admission.

PMID- 23864921
TI  - Delivery route following elective induction of labor at term: analysis of 807
      patients.
AB  - BACKGROUND: The purpose of this study is to compare mode of delivery for both
      nulliparous and multiparous women at term that underwent elective induction of
      labor to those who arrived in spontaneous labor. METHODS: Medical records of 807
      deliveries were reviewed. There were 566 labor patients and 241 elective
      induction patients. RESULTS: Women who underwent elective induction of labor were
      more likely to undergo cesarean delivery compared to those women who arrived in
      spontaneous labor (41.1% versus 9.9%, P = 0.001). This was true for both
      nulliparous women (49% versus 31%, P < 0.0001), and multiparous women (22.7%
      versus 1.6%, P < 0.0001). The rate of operative vaginal delivery was also
      increased in the elective induction of labor group (8.4% versus 3.6%, P <
      0.0001). Operative vaginal delivery was statistically significant in multiparous
      women (21% versus 4.1%, P < 0.0001), but not in nulliparous women (10.1% versus
      9.8%, P = NS). CONCLUSION: Elective induction of labor at term is associated with
      an increased risk of cesarean section in both nulliparous and multiparous women.
      There is also an increased risk of an operative vaginal delivery in multiparous
      women who underwent elective induction of labor.

PMID- 23864922
TI  - Efficacy of vitamin C vaginal tablets as prophylaxis for recurrent bacterial
      vaginosis: a randomised, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: The aetiology of bacterial vaginosis (BV) is still unclear but it is
      currently considered to be a synergistic polymicrobial syndrome. BV can often
      arise as a chronic or recurrent disease. The reason for such recurrences is not
      well elucidated. Previous studies have suggested that vaginal vitamin C may be a
      useful treatment in reducing recurrence rate, by increasing vaginal acidification
      and thereby making up for the decrease in hydrogen peroxide that results from a
      reduction in the number of lactobacilli present. Based on the above-mentioned
      consideration, a study was performed that aimed to evaluate the effect of vitamin
      C in the prophylaxis of BV relapses. METHODS: This was a randomised, double
      blind, placebo-controlled, parallel-group clinical trial. One hundred and forty
      two women, after having been cured from a recent episode of BV by either
      metronidazole or clindamycin, were randomised to receive vitamin C (74 patients)
      or placebo (68 patients) as prophylaxis for six monthly cycles, starting within
      24 hours of the determination of 'BV cure'. The patients applied one vaginal
      tablet once a day for 6 consecutive days per month after menses. RESULTS: The
      rate of BV recurrence during the first 3 months was considerably lower in the
      vitamin C group (6.8%) than in the placebo (14.7%) group. Considering a 6-month
      treatment period, the recurrence rate in the vitamin C group (16.2%) was
      significantly lower (P = 0.024) than in the placebo group (32.4%). Moreover, at
      the same time point, the survival analysis of Kaplan Meyer was significant in
      favour of the vitamin C group compared with the placebo group (P = 0.029).
      CONCLUSIONS: The study showed that regular use of 250 mg ascorbic acid vaginal
      tablets on 6 days per month for 6 months after successful treatment of bacterial
      vaginosis halves the risk of recurrence from 32.4% to 16.2% (P = 0.024).

PMID- 23864923
TI  - Sustained remission of antineutrophil cytoplasmic antibody-mediated
      glomerulonephritis and nephrotic syndrome in mixed connective tissue disease.
AB  - A woman diagnosed with mixed connective tissue disease (MCTD) developed an anti
      myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) and nephrotic
      syndrome with normal serum creatinine. Percutaneous kidney biopsy showed pauci
      immune glomerulonephritis with superimposed immune complex deposition. After
      treatment with cyclophophamide and prednisone, proteinuria decreased
      progressively to a level of 0.4 g/g creatinine, ANCA became undetectable, while
      serum creatinine remained normal seven years after the beginning of treatment.
      Sustained remission of nephrotic proteinuria with preserved renal function may
      follow treatment of ANCA-mediated disease developing in patients with MCTD. 

PMID- 23864924
TI  - Trends of ankylosing spondylitis ossification.

PMID- 23864926
TI  - Management of Medication-Related Cardiometabolic Risk in Patients with Severe
      Mental Illness.
AB  - Severe psychotic disorders, which on their own may be a risk factor for metabolic
      disorder and cardiovascular illness, are clinically compounded by the significant
      adverse side effects of antipsychotic medications. The majority of patients with
      severe psychotic disorders (i.e., schizophrenia, bipolar disorder, mania, and
      depression) must take antipsychotic medications to treat their psychoses and,
      subsequently, will require efficacious interventions to manage the metabolic
      consequences of pharmacologic treatment to mitigate excessive mortality
      associated with cardiovascular illness. We have reviewed the metabolic
      consequences of antipsychotic treatment and discussed pilot findings from a new
      nonpharmacologic intervention study looking at the clinical benefits of regular
      exercise as a management tool for the cardiometabolic risk factors in a cohort
      with severe mental illness.

PMID- 23864925
TI  - Optofluidics incorporating actively controlled micro- and nano-particles.
AB  - The advent of optofluidic systems incorporating suspended particles has resulted
      in the emergence of novel applications. Such systems operate based on the fact
      that suspended particles can be manipulated using well-appointed active forces,
      and their motions, locations and local concentrations can be controlled. These
      forces can be exerted on both individual and clusters of particles. Having the
      capability to manipulate suspended particles gives users the ability for tuning
      the physical and, to some extent, the chemical properties of the suspension
      media, which addresses the needs of various advanced optofluidic systems.
      Additionally, the incorporation of particles results in the realization of novel
      optofluidic solutions used for creating optical components and sensing platforms.
      In this review, we present different types of active forces that are used for
      particle manipulations and the resulting optofluidic systems incorporating them.
      These systems include optical components, optofluidic detection and analysis
      platforms, plasmonics and Raman systems, thermal and energy related systems, and
      platforms specifically incorporating biological particles. We conclude the review
      with a discussion of future perspectives, which are expected to further advance
      this rapidly growing field. 

PMID- 23864928
TI  - Boron-Based 4-Hydroxytamoxifen Bioisosteres for Treatment of de Novo Tamoxifen
      Resistant Breast Cancer.
AB  - Tamoxifen remains the first line therapy for estrogen receptor positive (ER+)
      breast cancer. However, polymorphisms of the gene encoding P450 2D6 could result
      in no protein expression or no CYP2D6 enzymatic activity and may significantly
      reduce the benefit of the hormone therapy. To address this issue, we designed and
      synthesized three 4-hydroxytamoxifen bioisosteres utilizing a boron-aryl carbon
      bond that can be oxidized under physiological conditions to yield 4
      hydroxytamoxifen. We show that the bioisosteres inhibit the growth of two ER+
      breast cancer cell lines, MCF-7 and T47D, with potencies comparable to or greater
      than that of 4-hydroxytamoxifen. We further demonstrate that after incubation
      with breast cancer cells, the majority of the bioisosteres has been converted to
      4-hydroxytamoxifen. Our study suggests that boron-based 4-hydroxytamoxifen
      bioisosteres may be an effective therapeutic remedy for intrinsic tamoxifen
      resistance in breast cancer patients deficient in CYP2D6 metabolism.

PMID- 23864927
TI  - Attenuation of beta-amyloid-induced oxidative cell death by sulforaphane via
      activation of NF-E2-related factor 2.
AB  - beta-amyloid peptide (Abeta), a major component of senile plaques, plays
      important roles in neuropathology of Alzheimer's disease (AD). An array of in
      vitro and in vivo data indicates that Abeta-induced neuronal death is mediated by
      oxidative stress. In this study, we aimed to investigate effects of sulforaphane
      (SUL), an isothiocyanate in cruciferous vegetables, on Abeta-induced oxidative
      cell death in SH-SY5Y cells. Cells treated with Abeta(25-35) exhibited decreased
      cell viability and underwent apoptosis as determined by MTT assay and TUNEL,
      respectively. Abeta(25-35)-induced cytotoxicity and apoptotic characteristics
      such as activation of c-JNK, dissipation of mitochondrial membrane potential,
      altered expression of Bcl-2 family proteins, and DNA fragmentation were
      effectively attenuated by SUL pretreatment. The antiapoptotic activity of SUL
      seemed to be mediated by inhibition of intracellular accumulation of reactive
      oxygen species and oxidative damages. SUL exerted antioxidant potential by
      upregulating expression of antioxidant enzymes including gamma-glutamylcysteine
      ligase, NAD(P)H:quinone oxidoreductase-1, and heme oxygenase-1 via activation of
      NF-E2-related factor 2(Nrf2). The protective effect of SUL against Abeta(25-35)
      induced apoptotic cell death was abolished by siRNA of Nrf2. Taken together, the
      results suggest that pharmacologic activation of Nrf2 signaling pathway by SUL
      might be a practical prevention and/or protective treatment for the management of
      AD.

PMID- 23864929
TI  - Urinary markers for bladder cancer.
AB  - Bladder cancer has the fifth highest incidence of all malignancies in the United
      States, with a propensity to recur, requiring lifelong surveillance after
      diagnosis. Urinary markers of disease have been of extreme interest in this field
      in an effort to simplify surveillance schedules and improve early detection of
      tumors. Many markers have been described, but most remain investigational.
      However, some markers have undergone clinical trials and are approved for
      clinical use. In this review, urinary markers and their application for screening
      and surveillance of bladder cancer are discussed. 

PMID- 23864930
TI  - Signalling mechanisms of long term facilitation of breathing with intermittent
      hypoxia.
AB  - Intermittent hypoxia causes long-term facilitation (LTF) of respiratory motor
      nerve activity and ventilation, which manifests as a persistent increase over the
      normoxic baseline for an hour or more after the acute hypoxic ventilatory
      response. LTF is likely involved in sleep apnea, but its exact role is uncertain.
      Previously, LTF was defined as a serotonergic mechanism, but new evidence shows
      that multiple signaling pathways can elicit LTF. This raises new questions about
      the interactions between signaling pathways in different time domains of the
      hypoxic ventilatory response, which can no longer be defined simply in terms of
      neurochemical mechanisms. 

PMID- 23864931
TI  - Management algorithm for genotype 1 hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection is the most common etiology of chronic liver
      disease in Western countries. Morbidity and mortality due to HCV-related end
      stage liver disease are increasing, just as novel therapeutics arrive with the
      promise of better cure rates that prevent these complications. However,
      substantial barriers to successful application of these novel treatments remain,
      including the lack of providers with sufficient knowledge to address this
      epidemic. To address these deficits, this article aims to provide a general
      framework with algorithms to guide initial management decisions for HCV genotype
      1 infection, the most commonly found genotype, based on therapies approved as of
      2013. 

PMID- 23864932
TI  - Recent advances in pediatric gastroenterology, hepatology and nutrition.
AB  - Pediatric gastroenterology, hepatology and nutrition are rapidly evolving,
      exciting and diverse disciplines. Because the field is so expansive, this
      commentary highlights important trends, rather than narrowly focusing on specific
      advances. Examples of advances in the highest impact and rapidly moving areas of
      pediatric gastroenterology are reviewed, including the intestinal microbiome,
      biomedical genomics, the biology of unique gastrointestinal cell types, and
      microRNAs (miRNAs). 

PMID- 23864933
TI  - Genetic Variation and Population Genetics of Taenia saginata in North and
      Northeast Thailand in relation to Taenia asiatica.
AB  - Taenia saginata is the most common human Taenia in Thailand. By cox1 sequences,
      73 isolates from four localities in north and northeast were differentiated into
      14 haplotypes, 11 variation sites and haplotype diversity of 0.683. Among 14
      haplotypes, haplotype A was the major (52.1%), followed by haplotype B (21.9%).
      Clustering diagram of Thai and GenBank sequences indicated mixed phylogeny among
      localities. By MJ analysis, haplotype clustering relationships showed paired
      stars-like network, having two main cores surrounded by minor haplotypes.
      Tajima's D values were significantly negative in T. saginata world population,
      suggesting population expansion. Significant Fu's F s values in Thai, as well as
      world population, also indicate that population is expanding and may be
      hitchhiking as part of selective sweep. Haplotype B and its dispersion were only
      found in populations from Thailand. Haplotype B may evolve and ultimately become
      an ancestor of future populations in Thailand. Haplotype A seems to be dispersion
      haplotype, not just in Thailand, but worldwide. High genetic T. saginata
      intraspecies divergence was found, in contrast to its sister species, T.
      asiatica; among 30 samples from seven countries, its haplotype diversity was
      0.067, while only 2 haplotypes were revealed. This extremely low intraspecific
      variation suggests that T. asiatica could be an endangered species. 

PMID- 23864934
TI  - Pattern Strabismus: Where Does the Brain's Role End and the Muscle's Begin?
AB  - Vertically incomitant pattern strabismus comprises 50% of infantile horizontal
      strabismus. The oblique muscle dysfunction has been associated with pattern
      strabismus. High-resolution orbit imaging and contemporary neurophysiology
      studies in non-human primate models of strabismus have shed light into the
      mechanisms of pattern strabismus. In this review, we will examine our current
      understanding of etiologies of pattern strabismus. Speculated pathophysiology
      includes oblique muscle dysfunction, loss of fusion with altered recti muscle
      pull, displacements and instability in connective tissue pulleys of the recti
      muscles, vestibular hypofunction, and abnormal neural connections. Orbital
      mechanical factors, such as abnormal pulleys, were reported as a cause of pattern
      strabismus in patients with craniofacial anomalies, connective tissue disorders,
      and late-onset strabismus. In contrast, abnormal neural connections could be
      responsible for the development of a pattern in infantile-onset strabismus.
      Pattern strabismus is likely multifactorial. Understanding the mechanisms of
      pattern strabismus is pivotal to determine an appropriate surgical treatment
      strategy for these patients. 

PMID- 23864935
TI  - Dried human amniotic membrane does not alleviate inflammation and fibrosis in
      experimental strabismus surgery.
AB  - Purpose. The purpose of this study was to evaluate the efficacy of dried human
      amniotic membrane (AM) in reducing the postoperative inflammatory response and
      scarring after strabismus surgery. Methods. The inflammatory response at the
      extraocular muscle reattachment site was analyzed after superior rectus (SR)
      resection in 12 rabbits. Dried human AM (Ambiodry2) was applied between the
      resected SR muscle plane and Tenon's capsule of the left eyes of rabbits. As a
      control, the right eyes of rabbits underwent SR resection only. The surgeon
      randomly ordered which eye gets operated first during the experiment. Two weeks
      later, enucleation was performed. Six sagittal sections were made for each eye at
      the insertion of the SR muscle. The grade of postoperative inflammation and the
      presence of fibrosis were evaluated in histological examinations. Results. There
      was no statistically significant difference in the intensity of inflammation and
      fibrous proliferation between the eyes treated with dried human AM after SR
      resection and those treated with SR resection only. Conclusions. The use of dried
      human AM was not effective in controlling the postoperative inflammation and
      scarring in rabbit eyes after extraocular muscle surgery. However, this may be
      due to the devitalized dry preparation of human AM (Ambiodry2), which may have
      lost the expected anti-inflammatory and anti-scarring properties, and further
      studies on humans may be necessary. 

PMID- 23864936
TI  - Multimodal imaging of the fundus.

PMID- 23864937
TI  - An Evaluation of Interindividual Responses to the Orally Administered
      Neurotransmitter beta -Alanine.
AB  - Previously, we have identified beta -alanine as a potential endogenous
      anticonvulsant molecule. beta -Alanine occurs within the human central nervous
      system and has been identified as both an inhibitory neuromodulator and
      neurotransmitter that is bioavailable to brain after oral administration. During
      preliminary compounding trials to ascertain dosing strategies for beta -alanine,
      we noted pronounced differences in the side effect profile experienced by
      individuals of Asian and Caucasian descent. To investigate whether ethnicity
      affects beta -alanine-induced side effects, we administered 3 g of beta -alanine
      in 200 mL of fruit drink to ten people of each ethnic background and observed
      them for 30 minutes. Data collected included basic physical statistics (height,
      age, and weight) and descriptions of all side effects, as reported by
      participants. We found that participants of Asian descent experienced
      paraesthesia, but significantly different in time of onset, intensity, and
      anatomical localization, as compared to the effects experienced by Caucasian
      participants. Since beta -alanine is an endogenous neurotransmitter substance
      within human brain, these side effect differences were unexpected. 

PMID- 23864938
TI  - Hypertension and cardiometabolic risk factors.

PMID- 23864939
TI  - Laryngeal manifestations of rheumatoid arthritis.
AB  - Rheumatoid arthritis is a destructive autoimmune disease that affects 3% of the
      adult population. It is characterized by the formation of both articular and
      extra-articular lesions with predilection for small joints. There are ubiquitous
      reports on the head and neck manifestations of RA with emphasis on the larynx.
      The laryngeal presenting features of this systemic disease may mimic a plethora
      of medical conditions, inflammatory and neoplastic. The main phonatory and
      respiratory symptoms are often subtle and misleading. This paper represents a
      literature review of the laryngeal manifestations of RA with emphasis on the
      clinical symptoms, laryngeal findings, diagnosis, and treatment. An early
      diagnosis of laryngeal involvement may prevent drastic complications. 

PMID- 23864940
TI  - Susceptibility for Lupus Nephritis by Low Copy Number of the FCGR3B Gene Is
      Linked to Increased Levels of Pathogenic Autoantibodies.
AB  - Low copy number (CN) of the FCGR3B gene reduces FCGR3B membrane expression on
      neutrophils and results in clearance of a smaller amount of immune complex. We
      investigated FCGR3B CN in relation to the clinical phenotype in a Caucasian SLE
      cohort (n = 107). FCGR3B CN was determined by three different qPCR parameter
      estimations (Ct-, Cy0, and cpD1) and confirmed by the FCGR2C/FCGR2A paralog ratio
      test. Clinical and serological data were then analyzed for their association with
      FCGR3B CN. Low FCGR3B CN (<2) was more frequent in SLE patients than in healthy
      controls (n = 162) (20% versus 6%, OR 4.15, P = 0.003) and associated with higher
      disease activity scores (SLEDAI 10.4 versus 6.1, P = 0.03), lupus nephritis (LN)
      (25 versus 5%, P = 0.03), and increased levels of antibodies against dsDNA (81
      versus 37 IU, P = 0.03), C1q (22 versus 6 IU, P = 0.003), and ribosomal P (10
      versus 5 IU, P = 0.01). No such associations were seen with antibodies against
      extractable nuclear antigens or high FCGR3B CN (>2). In multivariate analyses, LN
      was independently associated with anti-C1q-Ab levels (P = 0.03) and low FCGR3B CN
      (P = 0.09). We conclude that the susceptibility for LN in patients with low
      FCGR3B CN is linked to increased levels of pathogenic autoantibodies. 

PMID- 23864941
TI  - Prevalence and predictors of self-reported sexual abuse in severely obese
      patients in a population-based bariatric program.
AB  - BACKGROUND: Sexual abuse may be associated with poorer weight loss outcomes
      following bariatric treatment. Identifying predictors of abuse would enable
      focused screening and may increase weight management success. METHODS: We
      analyzed data from 500 consecutively recruited obese subjects from a population
      based, regional bariatric program. The prevalence of self-reported sexual abuse
      was ascertained using a single interview question. Health status was measured
      using a visual analogue scale (VAS). Multivariable logistic regression was
      performed to identify sexual abuse predictors. RESULTS: The mean age was 43.7 y
      (SD 9.6), 441 (88.2%) were females, 458 (91.8%) were white, and the mean body
      mass index (BMI) was 47.9 kg/m(2) (SD 8.1). The self-reported prevalence of past
      abuse was 21.8% (95% CI 18.4-25.4%). Abused subjects had worse health status (VAS
      score 53.1 (SD 21.2) versus 58.0 (SD 20.1), P = 0.03). BMI was not associated
      with abuse (P > 0.5). Age, sex, BMI, and covariate-adjusted independent
      predictors of abuse included alcohol addiction (adjusted odds ratio 15.8; 95% CI
      4.0-62.8), posttraumatic stress disorder (4.9; 2.5-9.5), borderline personality
      (3.8; 1.0-13.8), depression (2.4; 1.3-4.3), and lower household income (3.4; 1.6
      7.0). CONCLUSIONS: Abuse was common amongst obese patients managed in a
      population-based bariatric program; alcohol addiction, psychiatric comorbidities,
      and low-income status were highly associated with sexual abuse.

PMID- 23864942
TI  - Formation of short-chain Fatty acids, excretion of anthocyanins, and microbial
      diversity in rats fed blackcurrants, blackberries, and raspberries.
AB  - Introduction. Berries contain high amounts of dietary fibre and flavonoids and
      have been associated with improved metabolic health. The mechanisms are not clear
      but the formation of SCFAs, especially propionic and butyric acids, could be
      important. The potent antioxidant and antimicrobial properties of flavonoids
      could also be a factor, but little is known about their fate in the
      gastrointestinal tract. Aim. To compare how blackcurrants, blackberries,
      raspberries, and Lactobacillus plantarum HEAL19 affect formation of SCFAs,
      inflammatory status, caecal microbial diversity, and flavonoids. Results and
      Conclusions. Degradation of the dietary fibre, formation of SCFAs including
      propionic and butyric acids, the weight of the caecal content and tissue, and the
      faecal wet and dry weight were all higher in rats fed blackcurrants rather than
      blackberries or raspberries. However, the microbial diversity of the gut
      microbiota was higher in rats fed raspberries. The high content of soluble fibre
      in blackcurrants and the high proportion of mannose-containing polymers might
      explain these effects. Anthocyanins could only be detected in urine of rats fed
      blackcurrants, and the excretion was lower with HEAL19. No anthocyanins or
      anthocyanidins were detected in caecal content or blood. This may indicate uptake
      in the stomach or small intestine. 

PMID- 23864943
TI  - An Assessment of the Breastfeeding Practices and Infant Feeding Pattern among
      Mothers in Mauritius.
AB  - Proper breastfeeding practices are effective ways for reducing childhood
      morbidity and mortality. While many mothers understand the importance of
      breastfeeding, others are less knowledgeable on the benefits of breastfeeding and
      weaning. The aim in here is to assess breastfeeding pattern, infant formula
      feeding pattern, and weaning introduction in Mauritius and to investigate the
      factors that influence infant nutrition. 500 mothers were interviewed using a
      questionnaire which was designed to elicit information on infant feeding
      practices. Statistical analyses were done using SPSS (version 13.0), whereby chi
      square tests were used to evaluate relationships between different selected
      variables. The prevalence of breastfeeding practice in Mauritius has risen from
      72% in 1991 to 93.4% as found in this study, while only 17.9% breastfed their
      children exclusively for the first 6 months, and the mean duration of EBF
      (exclusive breastfeeding) is 2.10 months. Complementary feeding was more commonly
      initiated around 4-6 months (75.2%). Despite the fact that 60.6% of mothers
      initiate breastfeeding and 26.1% of mothers are found to breastfeed up to 2
      years, the practice of EBF for the first 6 months is low (17.9%). Factors found
      to influence infant feeding practices are type of delivery, parity, alcohol
      consumption, occupation, education, and breast problems. 

PMID- 23864945
TI  - Acute kidney injury in the critically ill patient.

PMID- 23864944
TI  - Engagement in HIV Medical Care and Technology Use among Stimulant-Using and
      Nonstimulant-Using Men who have Sex with Men.
AB  - Aims of this study were to assess the associations between stimulant use and
      attitudes toward and engagement in HIV medical care and to examine technology use
      among stimulant-using and nonstimulant-using men who have sex with men (MSM). HIV
      positive MSM (n = 276; mean age = 42 years; 71% white, non-Hispanic; 43% with
      college degree) completed an online survey in 2009. Most men (69%) had not missed
      any scheduled HIV medical appointments in the past year, while 23% had missed at
      least one, and 9% had not attended any appointments. Stimulant use was
      significantly associated with not attending any HIV medical appointments in the
      unadjusted model (relative risk ratio (RRR) = 2.84, 95% CI [1.07, 7.58]), as well
      as in models adjusted for demographic (RRR = 3.16, 95% CI [1.13, 8.84]) and
      psychosocial (RRR = 3.44, 95% CI [1.17, 10.15]) factors (Ps < 0.05). Fewer
      stimulant-using than non-stimulant-using men rated HIV medical care a high
      priority (57% versus 85%; P < 0.01). Few significant differences were found in
      online social networking or mobile phone use between stimulant-using and non
      stimulant-using MSM, even when stratified by engagement in HIV care. Findings
      indicate that stimulant use is uniquely associated with nonengagement in HIV
      medical care in this sample, and that it may be possible to reach stimulant-using
      MSM using online social networking and mobile technologies. 

PMID- 23864946
TI  - Development and preliminary testing of a framework to evaluate patients'
      experiences of the fundamentals of care: a secondary analysis of three stroke
      survivor narratives.
AB  - Aim. To develop and test a framework describing the interrelationship of three
      key dimensions (physical, psychosocial, and relational) in the provision of the
      fundamentals of care to patients. Background. There are few conceptual frameworks
      to help healthcare staff, particularly nurses, know how to provide direct care
      around fundamental needs such as eating, drinking, and going to the toilet.
      Design. Deductive development of a conceptual framework and qualitative analysis
      of secondary interview data. Method. Framework development followed by a
      secondary in-depth analysis of primary narrative interview data from three stroke
      survivors. Results. Using the physical, psychosocial and relational dimensions to
      develop a conceptual framework, it was possible to identify a number of
      "archetypes" or scenarios that could explain stroke survivors' positive
      experiences of their care. Factors contributing to suboptimal care were also
      identified. Conclusions. This way of thinking about how the fundamentals of care
      are experienced by patients may help to elucidate the complex processes involved
      around providing high quality fundamentals of care. This analysis illustrates the
      multiple dimensions at play. However, more systematic investigation is required
      with further refining and testing with wider healthcare user groups. The
      framework has potential to be used as a predictive, evaluative, and explanatory
      tool. 

PMID- 23864947
TI  - Retrospective cohort study of the prevalence of lumbosacral transitional vertebra
      in a wide and well-represented population.
AB  - Purpose. The aim of this study is to determine the prevalence of lumbosacral
      transitional vertebra (LSTV) in a well-represented general population. Methods.
      For a retrospective cohort study, abdominal radiographs of adult subjects were
      queried with clear visibility of the vertebral body articulation of the last rib,
      all lumbar transverse processes, and complete sacral wings. Exclusion criteria
      included any radiologic evidence of previous lumbosacral surgery that would block
      our view. A total of 6200 abdominal films were reviewed, and 3607 were identified
      as being suitable for the measurement of the desired parameters. Results. A total
      of 3607 subjects were identified as eligible for the study, and 683 (18.9%) were
      classified as positive for a lumbosacral transitional vertebra. The prevalence of
      sacralization and lumbarization was found as 17.2% and 1.7%, respectively. The
      average age at the time of the study was 39.5 +/- 15.2 years (18-86 years).
      Conclusions. As a result of different opinions, LSTV retains its controversial
      status. Our prevalence study of the general population will provide assistance
      for resolution of the controversy. Prevalence studies of the general population
      with a wide participation will shed light on comparative studies. 

PMID- 23864948
TI  - Differences in Mammalian target of rapamycin gene expression in the peripheral
      blood and articular cartilages of osteoarthritic patients and disease activity.
AB  - The gene expression of mTOR, autophagy-related ULK1, caspase 3, CDK-inhibitor
      p21, and TNF alpha was measured in the peripheral blood of osteoarthritic (OA)
      patients at different stages of the disease aiming to establish a gene expression
      profile that might indicate the activity of the disease and joint destruction.
      Whole blood of 65 OA outpatients, 27 end-stage OA patients, 27 healthy
      volunteers, and knee articular cartilages of 28 end-stage OA patients and 26
      healthy subjects were examined. OA outpatients were subjected to clinical
      testing, ultrasonography, and radiographic and WOMAC scoring. Protein levels of
      p70-S6K, p21, and caspase 3 were quantified by ELISA. Gene expression was
      measured using real-time RT-PCR. Upregulation of mTOR gene expression was
      observed in PBMCs of 42 OA outpatients ("High mTOR expression subset") and in
      PBMCs and articular cartilages of all end-stage OA patients. A positive
      correlation between mTOR gene expression in PBMCs and cartilage was observed in
      the end-stage OA patients. 23 OA outpatients in the "Low mTOR expression subset"
      exhibited significantly lower mTOR gene expression in PBMCs compared to healthy
      controls. These "Low mTOR" subset subjects experienced significantly more pain
      upon walking, and standing and increased total joint stiffness versus "High mTOR"
      subset, while the latter more often exhibited synovitis. The protein
      concentrations of p70-S6K, p21, and caspase 3 in PBMCs were significantly lower
      in the "Low" subset versus "High" subset and end-stage subjects. Increases in the
      expression of mTOR in PBMCs of OA patients are related to disease activity, being
      associated with synovitis more than with pain. 

PMID- 23864949
TI  - Association of the cardioankle vascular index and ankle-brachial index with
      carotid artery intima media thickness in hemodialysis patients.
AB  - The objectives of the present study are (1) to compare the cardioankle vascular
      index (CAVI), ankle-brachial index (ABI), and carotid artery intima-media
      thickness (CA-IMT) between HD patients with and without type 2 diabetes (T2D) or
      prevalence of cardiovascular (CV) disease and (2) also to evaluate the
      relationship of these indices with CA-IMT in these patients according to ABI
      levels. This study consisted of 132 HD patients with T2D and the same number of
      patients without T2D. The patients with diabetes or prevalence of CV disease had
      significantly higher CA-IMT and lower ABI values than those without diabetes or
      prevalence of CV disease, respectively. Although diabetic patients had higher
      CAVI than those without diabetes, CAVI did not differ between patients with or
      without prevalence of CV disease. In univariate analysis, CA-IMT was more
      strongly correlated with ABI than CAVI. However, the opposite was true in
      patients with an ABI value of more than 0.95. Both indices were significantly
      correlated with CA-IMT although ABI was a powerful determinant than CAVI. It
      appears that both indices are associated with CA-IMT in HD patients, especially
      with an ABI value of more than 0.95. 

PMID- 23864950
TI  - Integrity of the anterior visual pathway and its association with ambulatory
      performance in multiple sclerosis.
AB  - Background. Retinal nerve fiber layer thickness (RNFLT) and total macular volume
      (TMV) represent markers of neuroaxonal degeneration within the anterior visual
      pathway that might correlate with ambulation in persons with multiple sclerosis
      (MS). Objective. This study examined the associations between RNFLT and TMV with
      ambulatory parameters in MS. Methods. Fifty-eight MS patients underwent a
      neurological examination for generation of an expanded disability status scale
      (EDSS) score and measurement of RNFLT and TMV using optical coherence tomography
      (OCT). Participants completed the 6-minute walk (6MW) and the timed 25-foot walk
      (T25FW). The associations were examined using generalized estimating equation
      models that accounted for within-patient, inter-eye correlations, and controlled
      for disease duration, EDSS score, and age. Results. RNFLT was not significantly
      associated with 6MW (P = 0.99) or T25FW (P = 0.57). TMV was significantly
      associated with 6MW (P = 0.023) and T25FW (P = 0.005). The coefficients indicated
      that unit differences in 6MW (100 feet) and T25FW (1 second) were associated with
      0.040 and -0.048 unit differences in TMV (mm(3)), respectively. Conclusion.
      Integrity of the anterior visual pathway, particularly TMV, might represent a
      noninvasive measure of neuroaxonal degeneration that is correlated with
      ambulatory function in MS. 

PMID- 23864951
TI  - Chronic NaHS Treatment Is Vasoprotective in High-Fat-Fed ApoE(-/-) Mice.
AB  - Hydrogen sulfide is emerging as an important mediator of vascular function that
      has antioxidant and cytoprotective effects. The aim of this study was to
      investigate the role of endogenous H2S and the effect of chronic exogenous H2S
      treatment on vascular function during the progression of atherosclerotic disease.
      ApoE(-/-) mice were fed a high-fat diet for 16 weeks and treated with the H2S
      donor NaHS or the cystathionine- gamma -lyase (CSE) inhibitor D,L
      propargylglycine (PPG), to inhibit endogenous H2S production for the final 4
      weeks. Fat-fed ApoE(-/-) mice displayed significant aortic atherosclerotic
      lesions and significantly impaired endothelial function compared to wild-type
      mice. Importantly, 4 weeks of NaHS treatment significantly reduced vascular
      dysfunction and inhibited vascular superoxide generation. NaHS treatment
      significantly reduced the area of aortic atherosclerotic lesions and attenuated
      systolic blood pressure. Interestingly, inhibiting endogenous, CSE-dependent H2S
      production with PPG did not exacerbate the deleterious vascular changes seen in
      the untreated fat-fed ApoE(-/-) mice. The results indicate NaHS can improve
      vascular function by reducing vascular superoxide generation and impairing
      atherosclerotic lesion development. Endogenous H2S production via CSE is
      insufficient to counter the atherogenic effects seen in this model; however
      exogenous H2S treatment has a significant vasoprotective effect. 

PMID- 23864952
TI  - Bioremediating oil spills in nutrient poor ocean waters using fertilized clay
      mineral flakes: some experimental constraints.
AB  - Much oil spill research has focused on fertilizing hydrocarbon oxidising
      bacteria, but a primary limitation is the rapid dilution of additives in open
      waters. A new technique is presented for bioremediation by adding nutrient
      amendments to the oil spill using thin filmed minerals comprised largely of
      Fullers Earth clay. Together with adsorbed N and P fertilizers, filming
      additives, and organoclay, clay flakes can be engineered to float on seawater,
      attach to the oil, and slowly release contained nutrients. Our laboratory
      experiments of microbial activity on weathered source oil from the Deepwater
      Horizon spill in the Gulf of Mexico show fertilized clay treatment significantly
      enhanced bacterial respiration and consumption of alkanes compared to untreated
      oil-in-water conditions and reacted faster than straight fertilization. Whereas a
      major portion (up to 98%) of the alkane content was removed during the 1 month
      period of experimentation by fertilized clay flake interaction; the reduced
      concentration of polyaromatic hydrocarbons was not significantly different from
      the non-clay bearing samples. Such clay flake treatment could offer a way to more
      effectively apply the fertilizer to the spill in open nutrient poor waters and
      thus significantly reduce the extent and duration of marine oil spills, but this
      method is not expected to impact hydrocarbon toxicity. 

PMID- 23864953
TI  - Drug resistance and the role of combination chemotherapy in improving patient
      outcomes.
AB  - Resistance to cancer chemotherapy is a common phenomenon especially in metastatic
      breast cancer (MBC), a setting in which patients typically have had exposure to
      multiple lines of prior therapy. The subsequent development of drug resistance
      can result in rapid disease progression during or shortly after completion of
      treatment. Moreover, cross-class multidrug resistance limits patient treatment
      choices, particularly in a setting where treatments options are few. One attempt
      to minimize the impact of drug resistance has been the concurrent use of two or
      more chemotherapy agents with unrelated mechanisms of action and differing modes
      of drug resistance, with the intent of blocking the development of multiple
      intracellular escape pathways essential for tumor survival. Within the past
      decade, an array of mechanistically diverse agents has augmented the list of
      combination regimens that may be both synergistic and efficacious in pretreated
      MBC. The aim of this paper is to review mechanisms of resistance to common
      chemotherapy agents and to consider current combination treatment options for
      heavily pretreated and/or drug-resistant patients with MBC. 

PMID- 23864954
TI  - Pretreatment thrombocytosis as a prognostic factor in metastatic breast cancer.
AB  - Background. An elevated platelet count is often associated with malignancies, and
      it has been confirmed as an adverse prognostic factor in various cancers
      including early stage breast cancer. We sought to determine if thrombocytosis is
      also a prognostic factor in metastatic breast cancer. Patients and Methods. The
      records of 165 metastatic breast cancer patients with complete follow-up that had
      thrombocytosis or normal platelet counts were reviewed. Kaplan-Meier curves were
      constructed, and the survivals of the two groups were compared using the LogRank
      test. A Cox regression analysis was used to determine if thrombocytosis is an
      independent factor for overall and progression free survival. Results. There was
      a statistically significant difference in overall and progression free survival
      favoring the normal platelets group (LogRank test P = 0.038 and 0.008, resp.).
      Thrombocytosis remained a significant adverse prognostic factor in multivariate
      analysis. Other independent prognostic factors for overall survival included age,
      ER/PR status, and grade. Conclusion. Thrombocytosis represents an independent
      adverse prognostic factor in patients with metastatic breast cancer. Thus
      metastatic breast cancer joins a range of cancers in which this easily measurable
      value can be used for clinical prognostication. Further use as a predictive value
      for specific treatments has a rationale and deserves to be investigated. 

PMID- 23864955
TI  - Hemin and Zinc Protoporphyrin IX Affect Granisetron Constipating Effects In Vitro
      and In Vivo.
AB  - Granisetron is a 5-HT3 receptors antagonist used in the management of emesis
      associated with anticancer chemotherapy. It affects intestinal motility with
      constipating effect. Since the pathway heme oxygenase/carbon monoxide (HO/CO) is
      involved in gastrointestinal motility, we evaluated the possible interplay
      between granisetron and agents affecting HO/CO pathways such as zinc
      protoporphyrin IX (ZnPPIX), an HO inhibitor, or hemin, an HO-1 inducer. ZnPPIX
      (10 uM) or hemin (10 uM), but not granisetron (0.1, 0.3, 1 uM), affected
      spontaneous basal activity recorded in rat duodenal strips, in noncholinergic
      nonadrenergic conditions. Granisetron restored spontaneous basal activity after
      ZnPPIX, but not after hemin. ZnPPIX decreased and hemin increased the inhibition
      of activity after electrical field stimulation (EFS), but they did not affect the
      contraction that follows the relaxation induced by EFS called off contraction.
      Granisetron did not alter the response to EFS per se but abolished both ZnPPIX
      and hemin effect when coadministered. In vivo study showed constipating effect of
      granisetron (25, 50, 75 ug/kg/sc) but no effect of either ZnPPIX (50 ug/kg/i.p.)
      or hemin (50 uM/kg/i.p.). When coadministered, granisetron effect was abolished
      by ZnPPIX and increased by hemin. Specimens from rats treated in vivo with hemin
      (50 uM/kg/i.p.) showed increased HO-1 protein levels. In conclusion, granisetron
      seems to interact with agents affecting HO/CO pathway both in vitro and in vivo. 

PMID- 23864956
TI  - Bacteriological safety of blood collected for transfusion at university of gondar
      hospital blood bank, northwest ethiopia.
AB  - Background. Transfusion associated bacterial infection has remained more frequent
      with a sever risk of morbidity and mortality. This study assessed the
      bacteriological safety of blood collected for transfusion. Method. A cross
      sectional study was conducted at University of Gondar hospital blood bank from
      December 2011 to June 2012. Bacterial isolation, identification, and
      antimicrobial susceptibility tests were done as per the standard procedure. Chi
      square test and P value were used to assess associations between risk factors and
      the bacterial isolation rate. Results. Twenty-one (15.33%) blood units were found
      contaminated with bacteria, and 95.24% contamination was due to external sources.
      The commonly isolated bacteria were Staphylococcus aureus, Coagulase negative
      Staphylococci, Escherichia coli, Klebsiella species, Streptococci species,
      Enterobacter species, and Citrobacter species. All of the bacteria isolated were
      100% sensitive to Gentamicin, Chloramphenicol, Amoxicillin, and Doxycycline.
      Multiple antimicrobial resistances were observed in 66.7% of the isolates. Not
      using glove by phlebotomist, touching disinfected phlebotomy site and double
      puncture at the same hand or both hands of a donor were found to be risk factors
      for bacterial contamination. Conclusion. Bacterial contamination of blood to be
      transfused is a common problem in the hospital. So attention should be given to
      activities performed at the blood bank for safe transfusion practices. 

PMID- 23864957
TI  - Detection of minimal residual disease by flow cytometry for patients with
      multiple myeloma submitted to autologous hematopoietic stem cell transplantation.
AB  - The treatment strategy in multiple myeloma (MM) is to get complete remission
      followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell
      Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45(-/dim),
      CD38(+high), CD138(+), CD19(-), and  CD56(+high) in most cases. The description
      of this immunophenotype is of major importance as it leads to the correct
      identification of minimal residual disease (MRD). Samples from 44 Patients were
      analyzed prospectively in this study. We analyzed if the presence of MRD at three
      months after HSCT was predictive of relapse or death. There were 40 evaluable
      patients of whom 16/40 patients had MRD at three moths after HSCT and there were
      none in cytological relapse. The mean overall survival (OS) was 34 months and
      disease-free survival (RFS) was 28 months after HSCT. There was no significant
      difference in the log rank analysis comparing OS and the presence of MRD (P =
      0,611) and RFS (P = 0,3106). Here, we demonstrate that three color flow cytometry
      (FCM) is more sensitive for MDR evaluation than cytological analyzes. However,
      based in our data we can not affirm that MRD is a good predictor of MM relapse or
      death. In conclusion, our results could be attributed to a short followup, small
      sample size, and over most to the inability of a three-color FCM to detect the
      NPC population. 

PMID- 23864958
TI  - Prevalence and pattern of neurocognitive impairment in nigerians with stages 3 to
      5 chronic kidney disease.
AB  - Background. Cognitive impairment with its negative effect on quality of life has
      been reported in chronic kidney disease (CKD). The paucity of the literature on
      cognitive impairment in Africans with CKD prompted this study. Objectives. To
      determine the frequency and pattern of cognitive impairment in patients with
      stages 3 to 5 CKD. Methods. We studied 79 consecutive consenting adults with a
      National Kidney Foundation (NKF) stage 3 to 5 CKD based on their estimated
      glomerular filtration rate using the Cockcroft-Gault formula. The controls
      consisted of healthy demographically matched subjects. Community screening
      instrument for dementia (CSI'D), trail making test A (TMTA), and trail making
      test B (TMTB) were used for cognitive assessment. Results. More CKD patients had
      cognitive impairment compared with controls using CSI'D (51.9% versus 2.5%, P <
      0.001); TMTA (53.2% versus 0%, P < 0.001); and TMTB (40% versus 0%, P < 0.001).
      The odds of having cognitive impairment increased in the presence of CKD when
      assessed using CSI'D (OR = 2.026; CI = 1.607-2.555); TMTA (OR = 3.13; CI = 2.40
      4.09) and TMTB (OR = 3.22; CI = 2.42-4.25). CKD patients performed poorer on
      tests of executive function TMTA (P < 0.001) and TMTB (P < 0.001) while CSI'D
      showed significantly lower scores on multiple cognitive domains. Conclusions.
      Significant cognitive impairment in multiple domains exists among Nigerians with
      CKD. 

PMID- 23864959
TI  - Detection of otosclerosis-specific measles virus receptor (cd46) protein
      isoforms.
AB  - Genetic predisposition of otosclerosis has long been suspected, but unclarified.
      Unique coexpression pattern of measles virus receptor (CD46) splicing isoforms in
      the human otic capsule is assumed, since otosclerosis is a measles virus
      associated organ-specific disease. In order to identify CD46 involved in the
      pathogenesis of otosclerosis, we used representative groups of histologically
      diagnosed otosclerotic, nonotosclerotic, and normal stapes footplates (n = 109).
      Consecutive histopathological examinations and CD46-specific Western blot
      analysis were performed. Normal and nonotosclerotic stapes footplates showed
      consistent expression of the conventional c, d, e, f, and l CD46 isoforms. In
      contrast, four novel isoforms (os1-4) translated as intact proteins were
      additionally detected in each otosclerotic specimen. The study herein presented
      provides evidence for the otosclerosis-associated expression pattern of CD46.
      This finding might explain the organ-specific, virus-associated and autoimmune
      inflammatory pathogenesis of otosclerosis. Regarding our current knowledge, this
      is the first report that confirms the presence of four new disease-specific
      protein variants of CD46. 

PMID- 23864960
TI  - The role of dentate gyrus neurogenesis in neuropsychiatric disorders.

PMID- 23864961
TI  - Ultrasonic assessment of females with carpal tunnel syndrome proved by nerve
      conduction study.
AB  - INTRODUCTION: Carpal tunnel syndrome (CTS) is the most commonly diagnosed
      entrapment neuropathy of the upper extremity. The objective of this study was to
      diagnose CTS and to assess its severity using high resolution ultrasound (HRUS)
      depending on the results of nerve conduction study (NCS). METHODS: A prospective
      cross-sectional study, in which HRUS was performed at 63 wrists of 35 female
      patients with different severity of CTS (as proved by NCS). Furthermore, 40
      healthy volunteers (80 wrists) underwent the same tests as the patients and have
      been chosen to match the patients in gender, age, and body mass index (BMI). The
      cross section area (CSA) of the median nerve (MN) was obtained using HRUS at the
      carpal tunnel inlet by direct tracing method. RESULTS: There was a significant
      difference in the CSA of the MN at the tunnel inlet in CTS patients when compared
      with the control group. In fact, the CSA of the control group showed a
      significant difference from each of patients subgroups. Furthermore, a
      significant difference in the CSA was seen in between these subgroups. In
      conclusion, the US examination of the MN seems to be a promising method in
      diagnosing and grading of carpal tunnel syndrome.

PMID- 23864963
TI  - Management and followup of complicated crown fractures in young patients treated
      with partial pulpotomy.
AB  - Two cases of young patients with traumatized permanent teeth having complicated
      crown fractures are reported. Endodontic management included partial pulpotomy by
      the Cvek technique; restorative management included resin restoration and
      reattachment of the teeth fragments. Treatments were considered successful in all
      cases according to the following criteria: absence of clinical symptoms, absence
      of X-ray signs of pathology, and presence of pulpal vitality 6 to 25 months after
      treatment. 

PMID- 23864965
TI  - Basic fibroblast growth factor for treatment of onychomadesis with delayed
      regrowth of the nail.
AB  - Onychomadesis usually arises from an inflammation of the paronychium or as a
      result of blisters and hemorrhaging under a nail that has been struck or
      compressed. No documented interactions between basic fibroblast growth factor
      (bFGF) and onychomadesis have hitherto been reported. This case report describes
      a 25-year-old woman with onychomadesis following infection of the ingrown nail of
      her left thumb. After ten months of observation with no treatment showed no
      regrowth of her left thumbnail, the external use of bFGF and antibiotic ointment
      was started. One month later, nail regrowth was observed up to the halfway point
      of the nail bed, and after treatment for three months, the regrown nail reached
      the top of the nail bed. Both thumbnails now looked identical. This case suggests
      that external use of bFGF can promote nail regrowth in cases of onychomadesis
      with delayed regrowth of the nail. 

PMID- 23864964
TI  - Circummandibular wiring of symphysis fracture in a five-year-old child.
AB  - The treatment of pediatric maxillofacial fractures is unique due to the
      psychological, physiological, developmental, and anatomical characteristics of
      children. Method. This case report describes the management of symphysis fracture
      of mandible in a 5-year-old boy. The fracture was treated by acrylic splint with
      circummandibular wiring. Results. The splint was removed after 3 weeks. The
      patient had no complaints, and radiograph revealed a healed fracture. Conclusion.
      The clinical outcome in the present case indicates the management of mandibular
      fractures in pediatric patients using acrylic splint with circummandibular
      wiring. 

PMID- 23864966
TI  - Cerebral arterial thrombosis in ulcerative colitis.
AB  - Thrombosis, mainly venous, is a rare and well-recognized extraintestinal
      manifestation of inflammatory bowel disease (IBD). We describe a 25-year-old
      Caucasian man affected by ulcerative colitis and sclerosing cholangitis with an
      episode of right middle cerebral arterial thrombosis resolved by intraarterial
      thrombolysis. We perform a brief review of the International Literature. 

PMID- 23864967
TI  - Adderall induced acute liver injury: a rare case and review of the literature.
AB  - Adderall (dextroamphetamine/amphetamine) is a widely prescribed medicine for the
      treatment of attention-deficit/hyperactivity disorder (ADHD) and is considered
      safe with due precautions. Use of prescribed Adderall without intention to
      overdose as a cause of acute liver injury is extremely rare, and to our knowledge
      no cases have been reported in the English literature. Amphetamine is an
      ingredient of recreational drugs such as Ecstacy and is known to cause
      hepatotoxicity. We describe here the case of a 55-year-old woman who developed
      acute liver failure during the treatment of ADHD with Adderall. She presented to
      the emergency room with worsening abdominal pain, malaise, and jaundice requiring
      hospitalization. She had a past history of partial hepatic resection secondary to
      metastasis from colon cancer which was under remission at the time of
      presentation. She recovered after intensive monitoring and conservative
      management. Adderall should be used carefully in individuals with underlying
      liver conditions. 

PMID- 23864968
TI  - Expanding the BP1-BP2 15q11.2 Microdeletion Phenotype: Tracheoesophageal Fistula
      and Congenital Cataracts.
AB  - The proximal q arm of chromosome 15 contains breakpoint regions BP1-BP5 with the
      classic deletion of BP1-BP3 best known to be associated with Prader-Willi and
      Angelman syndromes. The region is approximately 500 kb and microdeletions within
      the BP1-BP2 region have been reported in patients with developmental delay,
      behavioral abnormalities, and motor apraxia as well as dysmorphic features
      including hypertelorism, cleft or narrow palate, ear abnormalities, and recurrent
      upper airway infections. We report two patients with unique, never-before
      reported 15q11.2 BP1-2 microdeletion syndrome findings, one with proximal
      esophageal atresia and distal tracheoesophageal fistula (type C) and one with
      congenital cataracts. Cataracts have been described in Prader-Willi syndrome but
      we could not find any description of cataracts in Angelman syndrome. Esophageal
      atresia and tracheoesophageal fistula have not been reported to our knowledge in
      either syndrome. A chance exists that both cases are sporadic birth defects;
      however, the findings of the concomitant microdeletion cannot be overlooked as a
      possible cause. Based on our review of the literature and the presentation of our
      patients, we recommend that esophageal atresia and distal tracheoesophageal
      fistula as well as congenital cataracts be included in the phenotypic spectrum of
      15q11.2 BP1-2 microdeletion syndrome. 

PMID- 23864969
TI  - Hidden under a Cauliflower-Like Skin Tumor: Chromoblastomycosis.
AB  - We present the case of an 80-year-old patient with a recurrent hyperpigmented and
      cauliflower-like skin tumor on the stump of his left index finger. Despite
      suggestive clinical appearance for chromoblastomycosis the tumor was initially
      clinically and also histopathologically misdiagnosed as recurrent squamous cell
      carcinoma. Due to a cardiogenic shock, the patient died shortly after the
      diagnosis of chromoblastomycosis, before adequate treatment could be introduced.
      In non-tropical regions chromoblastomycosis is an uncommon chronic fungal
      infection with Fonsecaea pedrosoi being the most prevalent etiological agent.
      Mostly lower extremities are involved. It is not unusual that, clinically, in the
      absence of pigmentation, and, histopathologically, because of
      pseudoepitheliomatous hyperplasia of the epidermis, chromoblastomycosis is
      confounded with squamous cell cancer, and delays in diagnosis of one to 3 years
      are common. Therefore, a high grade of clinical suspicion and inclusion of
      chromoblastomycosis in the differential diagnosis of pigmented skin tumors are
      important to initiate adequate therapy. Our case is remarkable in many aspects.
      The localization on an upper extremity and the grade of invasiveness with
      involvement of bone are unusual; furthermore the lack of a tropical travel
      history emphasizes that the infection almost surely occurred in Switzerland. 

PMID- 23864962
TI  - Noninvasive strategies to promote functional recovery after stroke.
AB  - Stroke is a common and disabling global health-care problem, which is the third
      most common cause of death and one of the main causes of acquired adult
      disability in many countries. Rehabilitation interventions are a major component
      of patient care. In the last few years, brain stimulation, mirror therapy, action
      observation, or mental practice with motor imagery has emerged as interesting
      options as add-on interventions to standard physical therapies. The neural bases
      for poststroke recovery rely on the concept of plasticity, namely, the ability of
      central nervous system cells to modify their structure and function in response
      to external stimuli. In this review, we will discuss recent noninvasive
      strategies employed to enhance functional recovery in stroke patients and we will
      provide an overview of neural plastic events associated with rehabilitation in
      preclinical models of stroke. 

PMID- 23864970
TI  - Purple urine bag syndrome may not be benign: a case report and brief review of
      the literature.
AB  - Purple urine bag syndrome (PUBS) is a rare condition in which there is purple
      discoloration of the urine with its collecting bag and associated tubing occurs.
      It is considered a benign condition. We report an unusual case of PUBS in an 87
      year-old female from nursing home who had a history of recurrent UTI. She also
      had a history of ureteral obstruction requiring left nephrostomy tube. She was
      brought to emergency department with altered mental status which developed five
      days after the occurrence of purple discoloration of the urinary bag. Her urine
      culture grew vancomycin-resistant Enterococci (VRE) and Pseudomonas aeruginosa.
      She died within three days of hospitalization despite intensive care in tertiary
      center. This case highlights that PUBS may not always be benign and should be
      approached on a case-by-case basis because it may signal the underlying UTI which
      might be very difficult to treat. Failure of recognition of this peculiar color
      early could delay the appropriate intervention leading to fatal complication.
      This case also represents the rare occurrence of PUBS in the setting of
      nephrostomy tube. 

PMID- 23864971
TI  - Clinical manifest x-linked recessive adrenoleukodystrophy in a female.
AB  - Adrenoleukodystrophy (ALD) is a rare X-linked inherited leukodystrophy with a
      reduced capacity for degradation of very long chain fatty acids (VLCFAs). The
      intracellular accumulation of VLCFA leads to demyelination in the central nervous
      system (CNS) and cell destruction in the adrenal glands. ALD primarily affects
      males; however, females may develop milder symptoms that may be difficult to
      recognize. The present report describes a 35-year-old female who experienced a
      feeling of heaviness in the upper and lower limbs, pain in both knees, and
      difficulty climbing stairs, running, and jumping. Clinical examination revealed
      decreased sensitivity in the feet, particularly to touch. Deep tendon reflexes in
      the lower limbs were brisk, and Babinski's sign was present bilaterally. Multiple
      sclerosis (MS) was excluded, and all clinical and biochemical tests were normal.
      After two years of progressing symptoms, the patient was reevaluated and plasma
      levels of VLCFA were found to be elevated. Seven years prior to this finding, the
      patient had been found to be heterozygous for the missense mutation c.1679C> T,
      p.Pro560Leu on the ABCD1 gene (ATP-Binding Cassette subfamily D1). In conclusion,
      the patient's symptoms could be attributed to ALD. The present case underlines
      the importance of reevaluating family history in women presenting with vague
      neurological symptoms. 

PMID- 23864972
TI  - Technical, Anatomical, and Functional Study after Removal of a Symptomatic
      Cavernous Angioma Located in Deep Wernicke's Territories with Cortico-Subcortical
      Awake Mapping.
AB  - Introduction. The subcortical region underneath Wernicke's area (WA) is a
      critical crossing of the eloquent language pathways involved in all semantic,
      phonological, syntactic, and working memory elaboration. We report the resection
      of a CA located underneath the dominant WA discussing the functional and
      anatomical evidence provided by fMRI, dissections with Klingler's technique, and
      intraoperative mapping during awake surgery. Case Report. A 64-year-old right
      handed female affected by daily complex focal seizures underwent f-MRI, showing
      language activations in the middle and inferior temporal gyri and an unusual free
      entry zone in the "classical" WA. The cortical intraoperative mapping partially
      confirmed the f-MRI results, and we approached the lesion directly through WA.
      Subcortical DES allowed the identification of the eloquent language pathways and
      the radical resection of the perilesional gliotic rim. The patient did not report
      deficits and she is seizures and drug free after 1-year surgery. Discussion.
      Cortical DES demonstrated the variability of the eloquent areas within the cortex
      of the dominant temporal lobe. The subcortical DES confirmed the crucial role in
      language elaboration and the anatomical course of the bundles underneath WA.
      Conclusions. Awake surgery with DES represents a reliable and dynamic technique
      also for safer and functional-customized resection of CAs. 

PMID- 23864973
TI  - Angiographic embolization of a postpartum vulvovaginal hematoma in a patient with
      situs inversus totalis: an effective second-line treatment.
AB  - Situs inversus totalis is a rare congenital anomaly where asymmetrical
      positioning of internal organs may affect the surgical and radiological
      management of certain conditions. Vulvovaginal hematoma is a life-threatening
      complication of vaginal delivery whose primary treatment usually consists of
      incision and drainage of the hematoma and ligation of the responsible vessels,
      followed by wound packing. Failure of these measures to control the bleeding was
      previously considered as an indication for laparotomy to perform bilateral
      hypogastric artery ligation and, if needed, a hysterectomy. Relative to major
      abdominal surgery, selective percutaneous angiographic embolization offers
      considerable advantages and significant less morbidity. Indeed, angiographic
      embolization is routinely used as a measure to control refractory pelvic
      bleeding, though the literature and experience in women with situs inversus
      totalis are scarce. In this paper, we report a case of postpartum vulvovaginal
      hematoma in a patient with situs inversus, refractory to conventional treatment,
      where arteriographic embolization was successfully used to control the bleeding.
      The management of this obstetrical complication and the use of this minimally
      invasive technique are also reviewed. To the best of our knowledge, this is the
      first report in the literature describing the feasibility of this technique in a
      patient with situs inversus totalis. 

PMID- 23864974
TI  - Foudroyant Course of an Extensive Clostridium septicum Gas Gangrene in a Diabetic
      Patient with Occult Carcinoma of the Colon.
AB  - Background. Spontaneous gas gangrene is a rare disease in which Clostridium
      septicum frequently can be detected. After an incubation period of 5-48 hours, a
      very painful swelling is accompanied by a rapidly spreading toxic-infectious
      clinical picture ultimately leading to septic shock and multiple organ failure.
      We present a case of a completely documented rare infectious disease with triage
      findings including initial vital signs, initial medical findings, and the
      emergency lab., radiological, intraoperative, histopathological, microbiological,
      and postmortem results. After initial diagnosis of the underlying disease, the
      patient has been immediately transferred to the operating theatre. The laboratory
      findings reflect the devastating effect of toxin alpha which is a toxin typically
      produced by C. septicum. The patient presented both an anaemia and a manifest
      coagulopathy as well as an onset of multiple organ failure. Despite the
      aggressive medical and surgical measures that have been taken, this patient could
      not be saved. Discussion. The case presented vividly emphasises the difficulty to
      identify these cases early enough to save a patient. This documentation may help
      health care providers to identify this life threatening disease as early as
      possible in future cases. 

PMID- 23864975
TI  - Apocrine carcinoma of breast: a case report with review of the literature.
AB  - Apocrine carcinoma is a very rare form of breast malignancy with an incidence of
      <1% of female invasive breast carcinoma. We report a case of apocrine carcinoma
      in a 42-year female with marked adenosis showing apocrine metaplasia and discuss
      the criteria to diagnose apocrine carcinoma with the emerging concept of androgen
      receptor positivity with its implication on treatment and management of the
      patient. 

PMID- 23864976
TI  - A rare case of systemic lupus erythematosus with chylous ascites and chylothorax.
AB  - During the course of the disease a patient with systemic lupus erythematosus
      (SLE) may develop inflammation of one or more serous membranes, resulting in
      pleural, peritoneal, or pericardial effusion. Chylous ascites and chylothorax
      have rarely been described in patients with SLE. Therefore, in parallel with the
      analysis of blood samples, detailed analysis of the effusions should be carried
      out. Supportive measures are often needed to relieve the symptoms of chylothorax
      or chylous ascites together with the treatment of the primary disease. The
      available literature had reported just 4 cases of chylous ascites and/or
      chylothorax in association with SLE, and this patient presented here is one of
      the rare cases apart from the reported ones. 

PMID- 23864977
TI  - Bouveret syndrome-the rarest variant of gallstone ileus: a case report and
      literature review.
AB  - We present a case report of a patient with Bouveret syndrome with interesting
      radiological findings and successful surgical treatment after failure of the
      endoscopic techniques. The report is followed by a review of the literature
      regarding the diagnostic means and proper treatment of this rare entity. Bouveret
      syndrome refers to the condition of gastric outlet obstruction caused by the
      impaction of a large gallstone into the duodenum after passage through a
      cholecystoduodenal fistula. Many endoscopic and surgical techniques have been
      described in the management of this syndrome. This is a case of a 78-year-old
      patient with severe medical history who presented in bad general condition with
      an 8-day history of nausea, multiple bilious vomiting episodes, anorexia,
      discomfort in the right hypochondrium and epigastrium, and fever up to 38,5
      degrees C. The diagnosis of Bouveret syndrome was set after performing the proper
      imaging studies. An initial endoscopic effort to resolve the obstruction was
      performed without success. Surgical treatment managed to extract the impacted
      gallstone through an enterotomy after removal into the first part of the jejunum.

PMID- 23864978
TI  - Cecal lipoma presenting as acute intestinal obstruction in an elderly woman: a
      case report.
AB  - Colonic lipomas are rare nonepithelial tumors that are usually detected
      incidentally during surgery or colonoscopy. Although lipomas generally remain
      asymptomatic, when they exceed 2 cm of diameter they may cause abdominal pain,
      obstruction, or intussusception. Here we present a case of an elderly woman
      referred by her general practitioner to a general hospital of Crete because of
      acute abdominal pain along with signs of intestinal obstruction and a positive
      history of appetite loss. Abdominal computed tomography was performed. To
      marginalise the risk of malignancy, a right hemicolectomy was performed.
      Histopathological examination of the resected specimen confirmed the diagnosis of
      cecal lipoma. 

PMID- 23864979
TI  - Pelvic mass 21 years after total hip arthroplasty.
AB  - Background. Long-term urologic complications after total hip arthroplasty are
      rare, and reports in the urologic literature are scant. We present a recent case
      and review the relevant literature. Case. A 77-year-old man was referred to the
      urology clinic for a single episode of gross painless hematuria, abnormal urine
      cytology, and pelvic mass. He had a significant smoking history. Surgical history
      included right total hip arthroplasty 21 years prior. Results. Pelvic ultrasound
      revealed a large mass abutting the right bladder wall. Subsequent computed
      tomography indicated that the mass was extrinsic to the bladder. Results of
      computed tomography-guided biopsy of the mass were consistent with foreign body
      granuloma. Surveillance imaging confirmed no growth or progression, and
      intervention was deferred. Conclusion. Long-term complications of total hip
      arthroplasty may present with signs and symptoms of urologic disease. Reports in
      the urologic literature are rare. 

PMID- 23864980
TI  - Failure of Urological Implants in Spinal Cord Injury Patients due to Infection,
      Malfunction, and Implants Becoming Obsolete due to Medical Progress and Age
      Related Changes in Human Body Making Implant Futile: Report of Three Cases.
AB  - Any new clinical data, whether positive or negative, generated about a medical
      device should be published because health professionals should know which devices
      do not work, as well as those which do. We report three spinal cord injury
      patients in whom urological implants failed to work. In the first, paraplegic,
      patient, a sacral anterior root stimulator failed to produce erection, and a drug
      delivery system for intracavernosal administration of vasoactive drugs was
      therefore implanted; however, this implant never functioned (and, furthermore,
      such penile drug delivery systems to produce erection had effectively become
      obsolete following the advent of phosphodiesterase type 5 inhibitors).
      Subsequently, the sacral anterior root stimulator developed a malfunction and the
      patient therefore learned to perform self-catheterisation. In the second patient,
      also paraplegic, an artificial urinary sphincter was implanted but the patient
      developed a postoperative sacral pressure sore. Eight months later, a suprapubic
      cystostomy was performed as urethral catheterisation was very difficult. The
      pressure sore had not healed completely even after five years. In the third case,
      a sacral anterior root stimulator was implanted in a tetraplegic patient in whom,
      after five years, a penile sheath could not be fitted because of penile
      retraction. This patient was therefore established on urethral catheter drainage.
      Later, infection with Staphylococcus aureus around the receiver block
      necessitated its removal. In conclusion, spinal cord injury patients are at risk
      of developing pressure sores, wound infections, malfunction of implants, and the
      inability to use implants because of age-related changes, as well as running the
      risk of their implants becoming obsolete due to advances in medicine. Some
      surgical procedures such as dorsal rhizotomy are irreversible. Alternative
      treatments such as intermittent catheterisations may be less damaging than
      bladder stimulator in the long term. 

PMID- 23864981
TI  - A Cough Deteriorating Gross Hematuria: A Clinical Sign of a Forthcoming Life
      Threatening Rupture of an Intraparenchymal Aneurysm of Renal Artery (Wunderlich's
      Syndrome).
AB  - Macroscopic hematuria regards the 4% to 20% of all urological visits. Renal
      artery aneurysms (RAAs) are detected in approximately 0.01%-1% of the general
      population, while intraparenchymal renal artery aneurysms (IPRAAs) are even more
      rarely detected in less than 10% of patients with RAAs. We present a case of a 58
      year-old woman that came into the emergency room (ER) complaining of a gross
      hematuria during the last four days. Although in the ER room the first urine
      sample was clear after a cough episode, a severe gross hematuria began which led
      to a hemodynamically unstable patient. Finally, a radical nephrectomy was
      performed, and an IPRAA was the final diagnosis. A cough deteriorating hematuria
      could be attributed to a ruptured intraparenchymal renal artery aneurysm, which
      even though constitutes a rare entity, it is a life-threatening medical
      emergency. 

PMID- 23864982
TI  - Coronary arteriovenous fistula secondary to percutaneous coronary intervention of
      chronic total occlusion.
AB  - This is a case report of a 61-year-old female presenting with ongoing chest pain
      in the setting of an NSTEMI with lateral ST-T changes. On attempting to open the
      left circumflex (LCX), it resulted in a proximal LCX dissection. The patient
      remained stable with no further chest pain. She was treated with IV Eptifibatide
      for 48 hours and restudied in 72 hours. Repeat coronary angiography showed a
      marginally improved proximal dissection plane with a coronary AV fistula. She was
      managed conservatively and discharged with a non-invasive assessment in 8 weeks.
      The patient had a negative stress echocardiogram and was managed with maximal
      medical therapy. 

PMID- 23864983
TI  - The therapeutic effect of adding dextromethorphan to clonidine for reducing
      symptoms of opioid withdrawal: a randomized clinical trial.
AB  - Background. Dextromethorphan is a noncompetitive N-methyl D-aspartate receptor
      antagonist that is clinically feasible for relieving the opioid withdrawal
      symptoms. This study compares the efficacy of a combination therapy with
      dextromethorphan and clonidine to treatment with clonidine alone. Methods and
      Materials. In this double-blind randomized clinical trial, patients were selected
      from inpatients of detox and rehabilitation ward of Razi Hospital, Tabriz, Iran.
      They were randomly allocated to two groups receiving either clonidine (0.4-1.2
      mg/day) or clonidine and dextromethorphan (300 mg/day). Withdrawal symptoms were
      evaluated in the first day of admission and again 24, 48, and 72 hours later.
      Results. Thirty male patients completed the trial in each group. Withdrawal
      symptoms began to decrease in the second day in patients receiving
      dextromethorphan and clonidine while patients receiving clonidine experienced the
      more severe symptoms in 72 hours. Analysis of variance of the symptom severity
      score revealed a significant group * time interaction (F = 14.25; P < 0.001), so
      that patients receiving dextromethorphan plus clonidine had milder symptoms
      during three days in all of the measurements compared to clonidine group.
      Conclusion. Combination therapy of dextromethorphan and clonidine would result in
      milder opioid withdrawal symptoms compared to clonidine alone with a reduction
      beginning at the second day. 

PMID- 23864984
TI  - The Social Attribution Task-Multiple Choice (SAT-MC): A Psychometric and
      Equivalence Study of an Alternate Form.
AB  - The Social Attribution Task-Multiple Choice (SAT-MC) uses a 64-second video of
      geometric shapes set in motion to portray themes of social relatedness and
      intentions. Considered a test of "Theory of Mind," the SAT-MC assesses implicit
      social attribution formation while reducing verbal and basic cognitive demands
      required of other common measures. We present a comparability analysis of the SAT
      MC and the new SAT-MC-II, an alternate form created for repeat testing, in a
      university sample (n = 92). Score distributions and patterns of association with
      external validation measures were nearly identical between the two forms, with
      convergent and discriminant validity supported by association with affect
      recognition ability and lack of association with basic visual reasoning. Internal
      consistency of the SAT-MC-II was superior (alpha = .81) to the SAT-MC (alpha =
      .56). Results support the use of SAT-MC and new SAT-MC-II as equivalent test
      forms. Demonstrating relatively higher association to social cognitive than basic
      cognitive abilities, the SAT-MC may provide enhanced sensitivity as an outcome
      measure of social cognitive intervention trials. 

PMID- 23864985
TI  - The effects of insufflation conditions on rat mesothelium.
AB  - Aim. The aim of this investigation was to examine the alterations in the
      peritoneum after cold dry CO2, heated dry CO2, and humidified heated CO2 at
      pressures equivalent to intraperitoneal pressures used in human laparoscopy.
      Methods. Eighteen rats were divided into 4 treatment groups-group 1: untreated
      control; group 2: insufflation with cold dry CO2; group 3: insufflation with
      heated, dry CO2; group 4: insufflation with heated and humidified CO2. The
      abdomen was insufflated to 5 mm/Hg (flow rate 50 mL/min) for 2 h. Twelve hours
      later, tissue samples were collected for analysis by light microscopy (LM) and
      scanning electron microscopy (SEM). Results. Group 1: no abnormalities were
      detected. Group 2: specimens revealed an inflammatory response with loss of
      mesothelium and mesothelial cell nuclei showing lytic change. Cells were rounded
      with some areas of cell flattening and separation. Group 3: some animals showed
      little or no alteration, while others had a mild inflammatory response.
      Mesothelial cells were rounded and showed crenation on the exposed surface. Group
      4: specimens showed little change from the control group. Conclusions. The LM
      results indicate that insufflations with heated, humidified CO2 are the least
      likely to induce mesothelial damage. 

PMID- 23864986
TI  - Protective Efficacy of the Calicivirus Valency of the Leucofeligen Vaccine
      against a Virulent Heterologous Challenge in Kittens.
AB  - Feline calicivirus (FCV) is a common feline pathogen with a potential for
      antigenic diversity. This study aimed to evaluate and characterize the protective
      efficacy of the FCV-F9 valency of a tetravalent vaccine, Leucofeligen, against
      challenge with an unrelated strain. Ten 9-week-old kittens were vaccinated while
      10 remained as unvaccinated controls. The vaccinated cats received Leucofeligen
      twice subcutaneously with a 3-week interval. Four weeks after the second
      vaccination, all cats were challenged with virulent heterologous FCV and followed
      up for 21 days, monitoring their general condition, clinical signs, and
      immunological responses. During the vaccination phase, rectal temperatures and
      body weights were indistinguishable between the two groups. Only vaccinated cats
      showed FCV-specific seroconversion (both total and neutralizing antibodies). In
      the first week after challenge, the vaccinated cats had an 82.6% reduction in
      median clinical score compared to controls. Leucofeligen was thus shown to
      provide a significant clinical protection to kittens challenged with heterologous
      virulent FCV. This protection was similar whether the cats had neutralizing
      antibody or not, indicating a key role for cellular immunity in the overall
      protection. This also suggests that previously reported seroneutralisation
      studies may underestimate the level of cross-protection against field strains
      obtained with this modified live FCV-F9 vaccine. 

PMID- 23864987
TI  - Patient And phaRmacist Telephonic Encounters (PARTE) in an underserved rural
      population with asthma: methods and rationale.
AB  - PURPOSE: Methods used to deliver and test a pharmacy-based asthma care telephonic
      service for an underserved, rural patient population are described. SUMMARY: In a
      randomized controlled trial (RCT), the Patient And phaRmacist Telephonic
      Encounters (PARTE) project is assessing the feasibility, acceptability, and
      preliminary impact of providing pharmacy-based asthma care service
      telephonically. The target audience is a low income patient population across a
      large geographic area served by a federally qualified community health center.
      Ninety-eight participants have been randomized to either standard care or the
      intervention group who received consultation and direct feedback from pharmacists
      via telephone regarding their asthma self-management and medication use.
      Pharmacists used a counseling framework that incorporates the Indian Health
      Services 3 Prime Questions and the RIM Technique (Recognition, Identification,
      and Management) for managing medication use problems. Pharmacists encouraged
      patients to be active partners in the decision-making process to identify and
      address the underlying cause of medication use problems. Uniquely, this trial
      collected process and summative data using qualitative and quantitative
      approaches. Pharmacists' training, the fidelity and quality of pharmacists'
      service delivery, and short term patient outcomes are being evaluated. This
      evaluation will improve our ability to address research challenges and
      intervention barriers, refine staff training, explore patient perspectives, and
      evaluate measures' power to provide preliminary patient outcome findings.
      CONCLUSION: A mixed method evaluation of a structured pharmacist intervention has
      the potential to offer insights regarding staff training, service fidelity and
      short term outcomes using quantitative and qualitative data in an RCT. Results
      will provide evidence regarding the feasibility and quality of carrying out the
      study and service delivery from the multiple perspectives of participants,
      clinicians, and researchers.

PMID- 23864988
TI  - What is It? Difficult to Pigeon Hole Tremor: a Clinical-Pathological Study of a
      Man with Jaw Tremor.
AB  - BACKGROUND: The phenomenology of tremor is broad and its classification is
      complicated. Furthermore, the full range of tremor phenomenology with respect to
      specific neurological and neurodegenerative diseases has not been fully
      elaborated. CASE REPORT: This right-handed man had a chief complaint of jaw
      tremor, which began approximately 20 years prior to death at age 101 years. He
      had been diagnosed with essential tremor (ET) by a local doctor. His examination
      at age 100 years was notable for marked jaw tremor at rest in the absence of
      other clear features of parkinsonism, mild kinetic tremor of the hands and, in
      the last year of life, a score of 22/41 on a cognitive screen. A senior movement
      disorder neurologist raised doubt about the "ET" diagnosis. The history and
      videotaped examination were reviewed by three additional senior tremor experts,
      who raised a number of diagnostic possibilities. A complete postmortem
      examination was performed by a senior neuropathologist, and was notable for the
      presence of tufted astrocytes, AT8-labeled glial cytoplasmic inclusions, and
      globose neuronal tangles. These changes were widespread and definitive. A
      neuropathological diagnosis of progressive supranuclear palsy was assigned.
      DISCUSSION: This case presents with mixed and difficult to clinically classify
      tremor phenomenology and other neurological findings. The postmortem diagnosis
      was not predicted based on the clinical features, and it is possible that it does
      not account for all of the features. The case raises many interesting issues and
      provides a window into the complexity of the interpretation, nosology, and
      classification of tremor phenomenology.

PMID- 23864989
TI  - Corticosteroid Induced, HHV-8 Positive Kaposi's Sarcoma in a Non-HIV Elderly
      Patient.
AB  - Kaposi's sarcoma (KS) was first described in 1872 by Moritz Kaposi. In 1994,
      Chang et al. first identified DNA sequences corresponding to human herpesvirus-8
      (HHV-8) in AIDS-associated Kaposi sarcoma biopsies. It is now believed that
      presence of HHV-8 is necessary but not sufficient to cause KS. Other factors like
      immunosuppressive therapy also play a role. We describe an HIV-negative elderly
      patient who developed KS of skin and mucous membrane after prolonged use of
      corticosteroids for knee pain. The patient was positive for HHV-8. 

PMID- 23864990
TI  - Report of three cases of unusual anterior abdominal wall defects in fallujah
      general hospital during the year 2010.
AB  - Abdominal wall defects occur when the normal sequence of the gastro intestinal
      tract development is interrupted. Gastroschisis represents a herniation of
      abdominal contents through a paramedian full-thickness abdominal wall fusion
      defect without involving the umbilical cord. Evisceration usually only contains
      intestinal loops and has no surrounding membrane unlike omphalocoele. It is
      unusual for a newborn with gastroschisis to have other serious birth defects.
      Neonates with gastroschisis have better prognosis than those with omphalocele.
      Very rarely is gastroschisis associated with herniation of other organs, and
      their presence makes the prognosis worse. I report three cases of unusual
      anterior abdominal wall defects during the year 2010, each having specific
      associated abnormalities. One was stillborn, and the other two died shortly after
      delivery. 

PMID- 23864991
TI  - Pilot study of congenital anomaly rates at birth in fallujah, iraq, 2010.
AB  - OBJECTIVES: To examine numbers of congenital anomaly (CA) at birth overall and by
      class in one clinic in Fallujah General Hospital, Fallujah, Iraq. STUDY DESIGN:
      All congenital anomaly birth referrals to one pediatric clinician at Fallujah
      General Hospital for an eleven month period beginning November 1, 2009 were
      recorded. This clinic was one of three clinics to which cases would be referred.
      RESULTS: There were 291 CA cases registered at birth in the period at the study's
      clinic. The total number of births recorded in the hospital over the period was
      6049. The CAs included 113 heart and circulatory system cases, 72 nervous system
      cases, 40 digestive system cases, 9 genitourinary cases, 6 ear, face and neck
      cases, 7 respiratory cases and 30 Down syndrome cases. CONCLUSION: Owing to
      difficulties establishing the exact number of births from which these cases were
      drawn, the exact rates cannot be precisely determined. Nevertheless, on the basis
      of reasonable assumptions relating to the activity of the clinic involved, these
      results support earlier epidemiological findings. On the basis of work reported
      elsewhere, the higher rates of congenital anomalies are believed to be caused by
      exposure to some genotoxic agent, possibly uranium.

PMID- 23864992
TI  - Islamic medicine and evolutionary medicine: a comparative analysis.
AB  - The advent of evolutionary medicine in the last two decades has provided new
      insights into the causes of human disease and possible preventative strategies.
      One of the strengths of evolutionary medicine is that it follows a multi
      disciplinary approach. Such an approach is vital to future biomedicine as it
      enables for the infiltration of new ideas. Although evolutionary medicine uses
      Darwinian evolution as a heuristic for understanding human beings' susceptibility
      to disease, this is not necessarily in conflict with Islamic medicine. It should
      be noted that current evolutionary theory was first expounded by various Muslim
      scientists such as al-Jahiz, al-Tusi, Ibn Khaldun and Ibn Maskawayh centuries
      before Darwin and Wallace. In this way, evolution should not be viewed as being
      totally antithetical to Islam. This article provides a comparative overview of
      Islamic medicine and Evolutionary medicine as well as drawing points of
      comparison between the two approaches which enables their possible future
      integration. 

PMID- 23864993
TI  - Neglected Basal cell carcinoma in axilla.
AB  - Basal cell carcinoma (BCC) is the most common skin cancer. The most significant
      risk factor is ultraviolet radiation and the most frequent site of BCC is head
      and neck, with around 75-80% occurring on face. BCC occurs infrequently in non
      sun-exposed skin. The axilla is one of the least sun-exposed areas of our body,
      and as such BCC at this site is very rare. We present a case of large neglected
      axillary BCC in a 35- year-old male. 

PMID- 23864994
TI  - Ethics of surrogacy: a comparative study of Western secular and islamic
      bioethics.
AB  - The comparative approach regarding the ethics of surrogacy from the Western
      secular and Islamic bioethical view reveals both commensurable and
      incommensurable relationship. Both are eager to achieve the welfare of the
      mother, child and society as a whole but the approaches are not always the same.
      Islamic bioethics is straightforward in prohibiting surrogacy by highlighting the
      lineage problem and also other social chaos and anarchy. Western secular
      bioethics is relative and mostly follows a utilitarian approach. 

PMID- 23864995
TI  - Achalasia cardia in infants: report of two cases.
AB  - Achalasia cardia is a neuromuscular disorder of unknown etiology involving the
      body of the esophagus and lower esophageal sphincter (LES). It is characterized
      by aperistalsis of the body of the esophagus and failure of relaxation of lower
      esophageal sphincter. It usually affects patients between the ages of 30 and 60
      years. It is unusual in childhood and extremely rare in infants. We report two
      cases of achalasia cardia in infants. Both cases were treated with open Heller's
      esophagocardiomyotomy with anti-reflux procedure. 

PMID- 23864996
TI  - A Pilot Trial of Jawarish Amla as Adjuvant to Anti-Tubercular Treatment Drugs for
      Control of Adverse Reactions in DOTS Regime in Pulmonary TB.
AB  - BACKGROUND AND OBJECTIVES: One of the greatest challenges of health care systems
      at the dawn of the 21st century is tuberculosis (TB). Drug resistant strains of
      TB are becoming a global public health risk. These strains commonly appear due to
      faulty therapies. Patients frequently stop treatment due to the toxicity of anti
      tubercular treatment (ATT) drugs. Amla (Emblica officinalis) is a well-known
      Unani single drug. Jawarish amla is a Unani compound formulation which is
      commonly used to administer amla. This study tested the efficacy of Jawarish amla
      as an adjuvant to ATT drugs in reducing their side effects. METHODOLOGY: Half of
      forty eligible pulmonary tuberculosis patients were randomly assigned to Test
      (Group B) and the other half to Control (Group A). Six grams of Jawarish amla
      twice daily was administered to the test group, and the same dosage of placebo
      was administered to control group along with directly observed treatment, short
      course chemotherapy (DOTS) for 60 days. Fisher exact test and paired t-test were
      applied for efficacy evaluation. Grading of symptoms was done to assess the
      toxicity of ATT and outcome of the adjuvant. RESULTS AND DISCUSSION: Significant
      improvements were observed in almost all subjective and objective parameters. The
      exceptions were serum creatine and serum uric acid, which showed non-significant
      slight elevations within normal limits. CONCLUSION: Jawarish amla was ascertained
      to be safe and effective adjuvant of DOTS in combating the adverse effects of ATT
      drugs.

PMID- 23864997
TI  - Management of breast cancer by vaccine: fact or fiction.
AB  - Breast cancer (BC) is the most common malignancy (75-80%) among women. Options
      for management of BC are multivariate. Available modalities include surgery,
      radiotherapy, chemotherapy and hormone therapy. Despite availability of improved
      therapeutic adjuncts, mortality from BC is 40%. Vaccination strategies against BC
      are emerging as a viable alternative. This review highlights the available
      results of this emerging therapeutic strategy. 

PMID- 23864998
TI  - Biomarkers of Cognitive Training Effects in Aging.
AB  - An increasing number of studies have relied on brain imaging to assess the
      effects of cognitive training in healthy aging populations and in persons with
      early Alzheimer's disease or mild cognitive impairment (MCI). At the structural
      level, cognitive training in healthy aging individuals has been associated with
      increased brain volume, cortical thickness, and density and coherence of white
      matter tracts. At the functional level, task-related brain activation (using fMRI
      and PET) and fluorodeoxyglucose positron emission tomography (FDG-PET) were found
      to be sensitive to the effects of training. In persons with MCI, cognitive
      training increased brain metabolism and task-related brain activation, whereas
      healthy older adults showed patterns of increased and decreased activation.
      Further studies are required to generalize these findings to larger groups and to
      investigate more diverse training protocols. Research will also need to address
      important methodological issues regarding the use of biomarkers in cognitive
      aging, including reliability, clinical validity, and relevance to the
      pathophysiological process.

PMID- 23864999
TI  - Engineering triiodothyronine (T3) nanoparticle for use in ischemic brain stroke.
AB  - A potential means of pharmacological management of ischemic stroke is rapid
      intervention using potent neuroprotective agents. Thyroid hormone (T3) has been
      shown to protect against ischemic damage in middle cerebral artery occlusion
      (MCAO) model of ischemic brain stroke. While thyroid hormone is permeable across
      the blood-brain barrier, we hypothesized that efficacy of thyroid hormone in
      ischemic brain stroke can be enhanced by encapsulation in nanoparticulate
      delivery vehicles. We tested our hypothesis by generating poly-(lactide-co
      glycolide)-polyethyleneglycol (PLGA-b-PEG) nanoparticles that are either coated
      with glutathione or are not coated. We have previously reported that glutathione
      coating of PLGA-PEG nanoparticles is an efficient means of brain targeted drug
      delivery. Encapsulation of T3 in PLGA-PEG delivery vehicle resulted in particles
      that were in the nano range and exhibited a zeta potential of -6.51 mV (uncoated)
      or -1.70 mV (coated). We observed that both glutathione-coated and uncoated
      nanoparticles are taken up in cells wherein they stimulated the expression of
      thyroid hormone response element driven reporter robustly. In MCAO model of
      ischemic stroke, significant benefit of administering T3 in nanoparticulate form
      was observed over injection of a T3 solution. A 34 % decrease in tissue
      infarction and a 59 % decrease in brain edema were seen upon administration of T3
      solution in MCAO stroke model. Corresponding measurements for uncoated T3
      nanoparticles were 51 % and 68 %, whereas for the glutathione coated were 58 %
      and 75 %. Our study demonstrates that using nanoparticle formulations can
      significantly improve the efficacy of neuroprotective drugs in ischemic brain
      stroke. 

PMID- 23865000
TI  - Validation of DM-Scan, a computer-assisted tool to assess mammographic density in
      full-field digital mammograms.
AB  - We developed a semi-automated tool to assess mammographic density (MD), a
      phenotype risk marker for breast cancer (BC), in full-field digital images and
      evaluated its performance testing its reproducibility, comparing our MD estimates
      with those obtained by visual inspection and using Cumulus, verifying their
      association with factors that influence MD, and studying the association between
      MD measures and subsequent BC risk. Three radiologists assessed MD using DM-Scan,
      the new tool, on 655 processed images (craniocaudal view) obtained in two
      screening centers. Reproducibility was explored computing pair-wise concordance
      correlation coefficients (CCC). The agreement between DM-Scan estimates and
      visual assessment (semi-quantitative scale, 6 categories) was quantified
      computing weighted kappa statistics (quadratic weights). DM-Scan and Cumulus
      readings were compared using CCC. Variation of DM-Scan measures by age, body mass
      index (BMI) and other MD modifiers was tested in regression mixed models with
      mammographic device as a random-effect term. The association between DM-Scan
      measures and subsequent BC was estimated in a case-control study. All BC cases in
      screening attendants (2007-2010) at a center with full-field digital mammography
      were matched by age and screening year with healthy controls (127 pairs). DM-Scan
      was used to blindly assess MD in available mammograms (112 cases/119 controls).
      Unconditional logistic models were fitted, including age, menopausal status and
      BMI as confounders. DM-Scan estimates were very reliable (pairwise CCC: 0.921,
      0.928 and 0.916). They showed a reasonable agreement with visual MD assessment
      (weighted kappa ranging 0.79-0.81). DM-Scan and Cumulus measures were highly
      concordant (CCC ranging 0.80-0.84), but ours tended to be higher (4%-5% on
      average). As expected, DM-Scan estimates varied with age, BMI, parity and family
      history of BC. Finally, DM-Scan measures were significantly associated with BC (p
      trend=0.005). Taking MD<7% as reference, OR per categories of MD were: OR7%
      17%=1.32 (95% CI=0.59-2.99), OR17%-28%=2.28 (95% CI=1.03-5.04) and OR>=29%=3.10
      (95% CI=1.35-7.14). Our results confirm that DM-Scan is a reliable tool to assess
      MD in full-field digital mammograms. 

PMID- 23865002
TI  - Long-term results of ipsilateral radiotherapy for tonsil cancer.
AB  - PURPOSE: WE EVALUATED THE EFFECTIVENESS AND SAFETY OF IPSILATERAL RADIOTHERAPY
      FOR THE PATIENT WITH WELL LATERALIZED TONSIL CANCER: not cross midline and <1 cm
      of tumor invasion into the soft palate or base of tongue. MATERIALS AND METHODS:
      From 2003 to 2011, twenty patients with well lateralized tonsil cancer underwent
      ipsilateral radiotherapy. Nineteen patients had T1-T2 tumors, and one patient had
      T3 tumor; twelve patients had N0-N2a disease and eight patients had N2b disease.
      Primary surgery followed by radiotherapy was performed in fourteen patients: four
      of these patients received chemotherapy. Four patients underwent induction
      chemotherapy followed by concurrent chemoradiotherapy (CCRT). The remaining two
      patients received induction chemotherapy followed by radiotherapy and definitive
      CCRT, respectively. No patient underwent radiotherapy alone. We analyzed the
      pattern of failure and complications. RESULTS: The median follow-up time was 64
      months (range, 11 to 106 months) for surviving patients. One patient had local
      failure at tumor bed. There was no regional failure in contralateral neck, even
      in N2b disease. At five-year, local progression-free survival, distant metastasis
      free survival, and progression-free survival rates were 95%, 100%, and 95%,
      respectively. One patient with treatment failure died, and the five-year overall
      survival rate was 95%. Radiation Therapy Oncology Group grade 2 xerostomia was
      found in one patient at least 6 months after the completion of radiotherapy.
      CONCLUSION: Ipsilateral radiotherapy is a reasonable treatment option for well
      lateralized tonsil cancer. Low rate of chronic xerostomia can be expected by
      sparing contralateral major salivary glands.

PMID- 23865001
TI  - Enhancement of radiation effect using beta-lapachone and underlying mechanism.
AB  - Beta-lapachone (beta-Lap; 3,4-dihydro-2, 2-dimethyl-2H-naphthol[1, 2-b]pyran-5,6
      dione) is a novel anti-cancer drug under phase I/II clinical trials. beta-Lap has
      been demonstrated to cause apoptotic and necrotic death in a variety of human
      cancer cells in vitro and in vivo. The mechanisms underlying the beta-Lap
      toxicity against cancer cells has been controversial. The most recent view is
      that beta-Lap, which is a quinone compound, undergoes two-electron reduction to
      hydroquinone form utilizing NAD(P)H or NADH as electron source. This two-electron
      reduction of beta-Lap is mediated by NAD(P)H:quinone oxidoreductase (NQO1), which
      is known to mediate the reduction of many quinone compounds. The hydroquinone
      forms of beta-Lap then spontaneously oxidizes back to the original oxidized beta
      Lap, creating futile cycling between the oxidized and reduced forms of beta-Lap.
      It is proposed that the futile recycling between oxidized and reduced forms of
      beta-Lap leads to two distinct cell death pathways. First one is that the two
      electron reduced beta-Lap is converted first to one-electron reduced beta-Lap,
      i.e., semiquinone beta-Lap (SQ)(.-) causing production of reactive oxygen species
      (ROS), which then causes apoptotic cell death. The second mechanism is that
      severe depletion of NAD(P)H and NADH as a result of futile cycling between the
      quinone and hydroquinone forms of beta-Lap causes severe disturbance in cellular
      metabolism leading to apoptosis and necrosis. The relative importance of the
      aforementioned two mechanisms, i.e., generation of ROS or depletion of
      NAD(P)H/NADH, may vary depending on cell type and environment. Importantly, the
      NQO1 level in cancer cells has been found to be higher than that in normal cells
      indicating that beta-Lap may be preferentially toxic to cancer cells relative to
      non-cancer cells. The cellular level of NQO1 has been found to be significantly
      increased by divergent physical and chemical stresses including ionizing
      radiation. Recent reports clearly demonstrated that beta-Lap and ionizing
      radiation kill cancer cells in a synergistic manner. Indications are that
      irradiation of cancer cells causes long-lasting elevation of NQO1, thereby
      sensitizing the cells to beta-Lap. In addition, beta-Lap has been shown to
      inhibit the repair of sublethal radiation damage. Treating experimental tumors
      growing in the legs of mice with irradiation and intraperitoneal injection of
      beta-Lap suppressed the growth of the tumors in a manner more than additive.
      Collectively, beta-Lap is a potentially useful anti-cancer drug, particularly in
      combination with radiotherapy. 

PMID- 23865003
TI  - The reasonable timing of the adjuvant radiotherapy in the treatment of uterine
      carcinosarcoma according to the surgical intent: suggestion based on progression
      patterns.
AB  - PURPOSE: We designed this study to identify and suggest the reasonable timing of
      adjuvant radiotherapy in the treatment of uterine carcinosarcoma according to the
      surgical intent and patterns of progression. MATERIALS AND METHODS: We
      retrospectively analyzed a total of 50 carcinosarcoma patients diagnosed between
      1995 and 2010. Among these 50 patients, 32 underwent curative surgery and 13
      underwent maximal tumor debulking surgery. The remaining five patients underwent
      biopsy only. Twenty-six patients received chemotherapy, and 15 patients received
      adjuvant radiotherapy. RESULTS: The median follow-up period was 17.3 months.
      Curative resection (p < 0.001) and stage (p < 0.001) were statistically
      significant factors affecting survival. During follow-up, 30 patients showed
      progression. Among these, eight patients (16.0%) had loco-regional progression
      only. The patients who had received adjuvant radiotherapy did not show loco
      regional progression, and radiotherapy was a significant negative risk factor for
      loco-regional progression (p = 0.01). The time to loco-regional progression was
      much earlier for non-curative than curative resection (range, 0.7 to 7.6 months
      vs. 7.5 to 39.0 months). CONCLUSION: Adjuvant radiotherapy in the treatment of
      carcinosarcoma might be related to a low loco-regional progression rate.
      Radiotherapy should be considered in non-curatively resected patients as soon as
      possible.

PMID- 23865004
TI  - Endoscopic findings of rectal mucosal damage after pelvic radiotherapy for
      cervical carcinoma: correlation of rectal mucosal damage with radiation dose and
      clinical symptoms.
AB  - PURPOSE: To describe chronic rectal mucosal damage after pelvic radiotherapy (RT)
      for cervical cancer and correlate these findings with clinical symptoms and
      radiation dose. MATERIALS AND METHODS: Thirty-two patients who underwent pelvic
      RT were diagnosed with radiation-induced proctitis based on endoscopy findings.
      The median follow-up period was 35 months after external beam radiotherapy (EBRT)
      and intracavitary radiotherapy (ICR). The Vienna Rectoscopy Score (VRS) was used
      to describe the endoscopic findings and compared to the European Organization for
      Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG)
      morbidity score and the dosimetric parameters of RT (the ratio of rectal dose
      calculated at the rectal point [RP] to the prescribed dose, biologically
      effective dose [BED] at the RP in the ICR and EBRT plans, alpha/beta = 3).
      RESULTS: Rectal symptoms were noted in 28 patients (rectal bleeding in 21
      patients, bowel habit changes in 6, mucosal stools in 1), and 4 patients had no
      symptoms. Endoscopic findings included telangiectasia in 18 patients, congested
      mucosa in 20, ulceration in 5, and stricture in 1. The RP ratio, BEDICR,
      BEDICR+EBRT was significantly associated with the VRS (RP ratio, median 76.5%;
      BEDICR, median 37.1 Gy3; BEDICR+EBRT, median 102.5 Gy3; p < 0.001). The VRS was
      significantly associated with the EORTC/RTOG score (p = 0.038). CONCLUSION: The
      most prevalent endoscopic findings of RT-induced proctitis were telangiectasia
      and congested mucosa. The VRS was significantly associated with the EORTC/RTOG
      score and RP radiation dose.

PMID- 23865005
TI  - Categorizing accident sequences in the external radiotherapy for risk analysis.
AB  - PURPOSE: This study identifies accident sequences from the past accidents in
      order to help the risk analysis application to the external radiotherapy.
      MATERIALS AND METHODS: This study reviews 59 accidental cases in two
      retrospective safety analyses that have collected the incidents in the external
      radiotherapy extensively. Two accident analysis reports that accumulated past
      incidents are investigated to identify accident sequences including initiating
      events, failure of safety measures, and consequences. This study classifies the
      accidents by the treatments stages and sources of errors for initiating events,
      types of failures in the safety measures, and types of undesirable consequences
      and the number of affected patients. Then, the accident sequences are grouped
      into several categories on the basis of similarity of progression. As a result,
      these cases can be categorized into 14 groups of accident sequence. RESULTS: The
      result indicates that risk analysis needs to pay attention to not only the
      planning stage, but also the calibration stage that is committed prior to the
      main treatment process. It also shows that human error is the largest contributor
      to initiating events as well as to the failure of safety measures. This study
      also illustrates an event tree analysis for an accident sequence initiated in the
      calibration. CONCLUSION: This study is expected to provide sights into the
      accident sequences for the prospective risk analysis through the review of
      experiences.

PMID- 23865006
TI  - The location of locoregional recurrence in pathologic T3N0, non-irradiated lower
      rectal cancer.
AB  - PURPOSE: To investigate the patterns of locoregional recurrence of pathologic
      T3N0 (pT3N0) lower rectal cancer omitting postoperative radiotherapy (RT) and
      explore the potential of modification of a RT field. MATERIALS AND METHODS: From
      Jan 2003 to Nov 2011, 35 patients omitting preoperative or postoperative RT for
      pT3N0 lower rectal cancer were included. We defined the lower rectal cancer as
      the tumor with the inferior margin located below the virtual line-a convergent
      level between rectal wall and levator ani muscle. All patients had radiologic
      examinations for recurrence evaluation during the follow-up duration. RESULTS:
      The median follow-up duration was 66.4 months (range, 1.4 to 126.1 months). Eight
      (22.9%) of the 35 patients had recurrence. Three (8.6%) was local recurrence (LR)
      only, 3 (8.6%) was distant metastasis (DM) only, and 2 (5.7%) was LR with DM. All
      LR were located at primary tumor sites. The overall survival rate, LR-free
      survival rate, and DM-free survival rate at 5 years was 79.8%, 83%, and 87%,
      respectively. All LR developed from tumors over 5 cm. However, there was no
      statistical significance (p = 0.065). There was no other risk factor for LR.
      CONCLUSION: Even though the patients included in this study had pathologically
      favorable pT3N0 rectal cancer, LR developed in 14.3% of patients. Most of the LR
      was located at primary tumor sites prior to surgery. Based on these findings, it
      might seem reasonable to consider postoperative RT with a smaller radiation field
      to the primary tumor site rather than the conventional whole pelvic irradiation.

PMID- 23865007
TI  - Comparison study of intensity modulated arc therapy using single or multiple arcs
      to intensity modulated radiation therapy for high-risk prostate cancer.
AB  - PURPOSE: Intensity modulated arc therapy (IMAT) is a form of intensity modulated
      radiation therapy (IMRT) that delivers dose in single or multiple arcs. We
      compared IMRT plans versus single-arc field (1ARC) and multi-arc fields (3ARC)
      IMAT plans in high-risk prostate cancer. MATERIALS AND METHODS: Sixteen patients
      were studied. Prostate (PTV P ), right pelvic (PTV RtLN ) and left pelvic lymph
      nodes (PTV LtLN ), and organs at risk were contoured. PTV P , PTV RtLN , and PTV
      LtLN received 50.40 Gy followed by a boost to PTV B of 28.80 Gy. Three plans were
      per patient generated: IMRT, 1ARC, and 3ARC. We recorded the dose to the PTV, the
      mean dose (D MEAN ) to the organs at risk, and volume covered by the 50% isodose.
      Efficiency was evaluated by monitor units (MU) and beam on time (BOT). Conformity
      index (CI), Paddick gradient index, and homogeneity index (HI) were also
      calculated. RESULTS: Average Radiation Therapy Oncology Group CI was 1.17, 1.20,
      and 1.15 for IMRT, 1ARC, and 3ARC, respectively. The plans' HI were within 1% of
      each other. The D MEAN of bladder was within 2% of each other. The rectum D MEAN
      in IMRT plans was 10% lower dose than the arc plans (p < 0.0001). The GI of the
      3ARC was superior to IMRT by 27.4% (p = 0.006). The average MU was highest in the
      IMRT plans (1686) versus 1ARC (575) versus 3ARC (1079). The average BOT was 6
      minutes for IMRT compared to 1.3 and 2.9 for 1ARC and 3ARC IMAT (p < 0.05).
      CONCLUSION: For high-risk prostate cancer, IMAT may offer a favorable dose
      gradient profile, conformity, MU and BOT compared to IMRT.

PMID- 23865008
TI  - The code of ethics for nurses.
AB  - Nurses are ever-increasingly confronted with complex concerns in their practice.
      Codes of ethics are fundamental guidance for nursing as many other professions.
      Although there are authentic international codes of ethics for nurses, the
      national code would be the additional assistance provided for clinical nurses in
      their complex roles in care of patients, education, research and management of
      some parts of health care system in the country. A national code can provide
      nurses with culturally-adapted guidance and help them to make ethical decisions
      more closely to the Iranian-Islamic background. Given the general acknowledgement
      of the need, the National Code of Ethics for Nurses was compiled as a joint
      project (2009-2011). The Code was approved by the Health Policy Council of the
      Ministry of Health and Medical Education and communicated to all universities,
      healthcare centers, hospitals and research centers early in 2011. The focus of
      this article is on the course of action through which the Code was compiled,
      amended and approved. The main concepts of the code will be also presented here.
      No doubt, development of the codes should be considered as an ongoing process.
      This is an overall responsibility to keep the codes current, updated with the new
      progresses of science and emerging challenges, and pertinent to the nursing
      practice. 

PMID- 23865009
TI  - Implementation of Patient's Rights Charter: a Report from Ministry of Health and
      Medical Education, Iran.
AB  - At the aim of explaining the rights of health care recipients and upgrading
      ethical observance in the field of treatment-the most important field of health
      care-, the Patient's Rights Charter was declared by Ministry of Health and
      Medical Education to all medical universities in September 2009. This paper
      provides a report of strategic planning for implementation of Patient's Rights
      Charter and a summary of other projects. 

PMID- 23865010
TI  - Iran health system reform plan methodology.
AB  - BACKGROUND: The Ministry of Health and Medical Education of Iran, along with the
      country movement towards achievements of Iran's Vision 2025 put compilation of
      the health system reform plan on its agenda. In this article, we are trying to
      show the method we used for developing this plan and how this method considered
      the general condition of the country along with maintaining the standards of
      scientific and technical programs. All steps of this planning are described in
      the paper and finally we discuss the techniques and the appropriateness of the
      method compare with the experience of the other countries.

PMID- 23865011
TI  - Health system vision of iran in 2025.
AB  - BACKGROUND: Vast changes in disease features and risk factors and influence of
      demographic, economical, and social trends on health system, makes formulating a
      long term evolutionary plan, unavoidable. In this regard, to determine health
      system vision in a long term horizon is a primary stage. METHOD: After narrative
      and purposeful review of documentaries, major themes of vision statement were
      determined and its context was organized in a work group consist of selected
      managers and experts of health system. Final content of the statement was
      prepared after several sessions of group discussions and receiving ideas of
      policy makers and experts of health system. RESULTS: Vision statement in
      evolutionary plan of health system is considered to be :"a progressive community
      in the course of human prosperity which has attained to a developed level of
      health standards in the light of the most efficient and equitable health system
      in visionary region(1) and with the regarding to health in all policies,
      accountability and innovation". An explanatory context was compiled either to
      create a complete image of the vision. CONCLUSION: Social values and leaders'
      strategic goals, and also main orientations are generally mentioned in vision
      statement. In this statement prosperity and justice are considered as major
      values and ideals in society of Iran; development and excellence in the region as
      leaders' strategic goals; and also considering efficiency and equality, health in
      all policies, and accountability and innovation as main orientations of health
      system.

PMID- 23865012
TI  - Future of health care delivery in iran, opportunities and threats.
AB  - BACKGROUND: The aim of this study was to determine the impact of important social
      and technological trends on health care delivery, in the context of developing
      "Iran's Health System Reform Plan by 2025". METHODS: A detailed review of the
      national and international literature was done to identify the main trends
      affecting health system. To collect the experts' opinions about important trends
      and their impact on health care delivery, Focus Group Discussions (FGDs) and semi
      structured in-depth interviews techniques were used. The study was based on the
      STEEP model. Final results were approved in an expert's panel session. RESULTS:
      The important social and technological trends, affecting health system in Iran in
      the next 15 years are demographic transition, epidemiologic transition,
      increasing bio-environmental pollution, increasing slums, increasing private
      sector partnership in health care delivery, moving toward knowledge-based
      society, development of information and communication technology, increasing use
      of high technologies in health system, and development of traditional and
      alternative medicine. The opportunities and threats resulting from the above
      mentioned trends were also assessed in this study. CONCLUSION: Increasing
      healthcare cost due to some trends like demographic and epidemiologic transition
      and uncontrolled increase in using new technologies in health care is one of the
      most important threats that the health system will be facing. The opportunities
      that advancement in technology and moving toward knowledge-based society create
      are important and should not be ignored.

PMID- 23865013
TI  - Intersectoral collaboration to develop health equity indicators in iran.
AB  - BACKGROUND: Health equity is considered as one of the main objectives of health
      care systems. This study was carried out with the aim of determining health
      equity indicators in Iran. Through consideration of these indicators, differences
      in health status of different social groups and different geographical areas can
      be shown in different periods and based on that, effective interventions can be
      designed. This study is carried out through a main workshop and expert panels and
      final consensus on selected indicators. The first draft of indicators and
      inequity stratifying variables were prepared and then revised by working groups
      consisting of experts inside and outside Health system. Finally ideas were
      accepted or rejected after presenting enough reasons and deep examination through
      the Consensus-Oriented Decision-Making (COMD) model. Fifty two indicators have
      been determined as health equity indicators in five areas including health,
      social and human development, economic development, physical environment and
      infrastructure and governance. Furthermore, for each indicator the proper and
      practical stratifying variables of inequity were identified. By calculating such
      indicators, it becomes possible to determine differences in health status of
      different social groups and different geographical areas.

PMID- 23865014
TI  - Ways to improve the current performance of the boards of trustees of medical
      universities in iran.
AB  - BACKGROUND: Establishment of boards of trustees for all universities was
      legalized in 1988. It is crucial to assess the performance of the boards and to
      adjust them to the mandates raised by new visions of the country. METHODS:
      Subjects were members of boards of trustees and officers in charge of board's
      affairs at medical universities. Furthermore, a sample of 860 resolutions adopted
      by the boards was selected to assess the state of their enforcement. RESULTS:
      About 70% of the resolutions addressed have been enforced. There is a consensus
      on focusing on policy-making and high supervision on the objectives of the
      institutes rather than other areas. Furthermore, ways suggested improving the
      performance of the boards. CONCLUSION: Despite the rather high enforcement rate
      of the resolution in the past ten years, several interventions are suggested to
      improve the current performance of the boards of trustees and to meet new
      directions.

PMID- 23865015
TI  - Health in the 5th 5-years Development Plan of Iran: Main Challenges, General
      Policies and Strategies.
AB  - Access to the right to the highest attainable level of health is a constitutional
      right that obliges governments and other players to take step to increase all
      individuals' chances of obtaining good health. At the least, health and education
      are two crucial requirements for this as well. Iran's vision 2025 is going to
      lead the country to a developed state with the highest rank of economic,
      scientific and technological status in the region. Enjoying health, welfare, food
      security, social security, equal opportunities, etc, are also considered as part
      of characteristics of Iranian society in 2025. Although health system of Iran has
      many achievements in providing health services specially for the poor following
      the Islamic Revolution of 1979, but the evidences gathered to develop the 5(th) 5
      years economical, social and cultural plan (5(th)5YDP:2011-2015), listed a
      variety of main challenges in stewardship, financing, resources generation and
      service provision functions of the existing health system. Thus, to overcome the
      main challenges, about 11% of general policies of 5(th)5YDP are directly address
      health related issues with emphasizing on healthy human and comprehensive health
      approach with considering: Integration of policy making, planning, evaluation,
      supervision and public financing; Developing both quantity and quality of health
      insurance system and reducing out-of-pocket expenditures for health services to
      30% by the end of the 5th plan. The strategies of 5(th)5YDP adopted by the
      parliament as an Act will change the health system fundamentally through tuning
      the main drivers; so, its implementation needs brave leaders, capable managers,
      motivated technical staff and social mobilization. 

PMID- 23865016
TI  - Development and implementation of health technology assessment: a policy study.
AB  - BACKGROUND: To provide an overview of the development of health technology
      assessment (HTA) in Iran since 2007, and to facilitate further development of HTA
      and its integration into policy making. METHODS: Data of this study were
      collected through key documents (e.g. literature, laws, and other official
      documentation) and analyzed by experts of opinion in form of qualitative methods.
      RESULTS: Health technology assessment entered to the political agenda in Iran
      only in 2007 with a strong impetus of an evidence-based medicine movement with
      the bellow objectives: Institutionalization of evidence-based decision making in
      Ministry of Health, Creating an localization for structural HTA in Health system
      of Iran, Setting up training courses in order to educate capable manpower to full
      up the capacity of the universities, Establishment of a new field in HTA subject
      in medical universities for MSc and PhD degree, International communication about
      HTA through national website and possible participation in international
      Congress. CONCLUSION: HTA has been established in the healthcare system of Iran
      but what is needed is a clear political will to push forward the objectives of
      HTA in Iran. Similar to other countries, advance the regulation on the adoption
      of new health technologies to improve not only technical or allocate efficiency,
      but also health equity.

PMID- 23865017
TI  - Trend of knowledge production of research centers in the field of medical
      sciences in iran.
AB  - Establishment of medical research centers at universities and health-related
      organizations and annually evaluation of their research activities was one of the
      strategic policies which followed by governmental organization in last decade in
      order to strengthening the connections between health research system and health
      system. The aim of this study is to scrutinize the role of medical research
      centers in medical science production in Iran. This study is a cross sectional
      which has been performed based on existing reports on national scientometrics and
      evaluation results of research performance of medical research centers between
      years 2001 to 2010. During last decade number of medical research centers
      increased from 53 in 2001 to 359 in 2010. Simultaneous scientific output of
      medical research centers has been increased especially articles indexed in ISI
      (web of science). Proper policy implementation in the field of health research
      system during last decades led to improving capacity building and growth
      knowledge production of medical science in recent years in Iran. The process
      embedding research into the health systems requires planning up until research
      products improves health outcomes and health equity in country. 

PMID- 23865018
TI  - The analysis of health research system evaluation in medical sciences
      universities.
AB  - BACKGROUND: Based on Iran by 2025 defined vision, we must to receive the first
      grade of science position in south western Asian region. Thus we need to have a
      comprehensive evaluation program. METHODS: A comprehensive WHO Health Research
      System Analysis (HRSA)- based evaluation system was developed to evaluate the HRS
      in Iran. This article has explored the results of the five-year evaluation (2003
      2008) and aims to introduce this method to other developing countries. Here we
      explore the results of research performance evaluation from 2002 to 2010 and by
      comparing the results with previous available information, we reveal the probable
      role of this method in research promotion and proposed approach to facilitate and
      expedite achieving the prospects for goals of health research based on the
      visions of Iran by 2025. RESULTS: All of the indicators of stewardship and
      capacity building axes are received to their predefined levels. Moreover all of
      the medical science university research policies are based on their strategic
      plannings which are extracted from national visions of Iran by 2025. Most of the
      predefined goals in knowledge production domain had a significant grow trend but
      for more growth for commitments they should be closely follow. CONCLUSION: We
      developed an HRS-based comprehensive evaluation program to our national vision as
      well as our regional and international research competition.

PMID- 23865019
TI  - Designing a minimum data set for breast cancer: a starting point for breast
      cancer registration in iran.
AB  - BACKGROUND: Due to the high incidence of deaths from breast cancer, high cost of
      treatment and limited resources, the need to formulate and implement effective
      programs in reducing the burden of disease is obvious. Care, control and creation
      of cancer information system having an infrastructure from collection of minimum
      data sets (MDS) are the top priorities of research in Iran's Ministry of Health.
      METHODS: This is an applied descriptive research with comparative approach
      implemented in 2010. MDS for breast cancer on selected countries were searched
      and reviewed and proposed model based on the country's need was designed.
      Research data were implemented in 2 stages; assessment of MDS on selected
      countries and the validation of the proposed model through several meetings that
      has been carried out by the Undersecretary for Research and Technology and
      several oncologists and pathologists. RESULTS: The MDS is composed of 11
      parameters in the form of fields in closed structured arrangements with
      consideration to coding responses. These parameters include: hospital data,
      demography, referral, physical examination and investigation, diagnostic
      information, pathology, treatment, palliative care, completion of primary
      treatment, clinical trials and follow-up. This form is available for use in the
      cancer registry database. CONCLUSION: MDS provides an opportunity to strengthen
      communication between performed researches and research results for the
      improvement of programs, policies and strategies and provides positive effect on
      equality in the health system. Although the stages of creating the MDS for breast
      cancer has been successful, but many challenges has been met until its
      completion.

PMID- 23865020
TI  - The evaluation of international relationship role in promotion of health system
      research.
AB  - BACKGROUND: Regarding the need for scientific development and achievement our
      national goals, it is clear that international cooperation has the main role in
      this way. Here is a report on what we have done during past almost 10 years (2001
      2011) in the field of international medical research activities in Deputy
      Ministry for Research & Technology, Ministry of Health, Iran. Our effort was
      focused to identify and contact with the prominent scientific centers among the
      world where could make a connection between our researchers in medical science
      universities with those centers.

PMID- 23865021
TI  - Iranian Health Research Networks and Vision of Iran by 2025: A Case of Virtual
      Health Network in EMRI.
AB  - BACKGROUND: The present paper aims to explore the role of Health Research
      Networks (HRN) in facilitating and expedite achieving the prospects for goals of
      health research based on the visions of Iran by 2025. METHODS: Aiming to the main
      function of HSR to achieve the targeted conducting of health sciences research;
      more cooperation and coordination between health science researchers; avoid
      parallel investigations; and optimum utilization and appropriate distribution of
      resources, in 2000 the deputy of Research and Technology of Ministry of Health
      and Medical Education defined and developed a comprehensive HRN. RESULT: There
      are currently 27 research networks operating under the supervision of the Deputy
      of Research and Technology at MOHME. All of the HRN policies are following based
      on their strategic planning's which are extracted from national visions of Iran
      by 2025. CONCLUSION: Promoting the current position needs a reliable and feasible
      new strategies. The present article introduces the lessons learned of our
      experience in virtual web-based health research networking in Endocrinology and
      Metabolism Research Institute (EMRI).

PMID- 23865022
TI  - Health observatories in iran.
AB  - BACKGROUND: The Islamic Republic of Iran, in her 20 year vision by the year 2025,
      is a developed country with the first economic, scientific and technological
      status in the region, with revolutionary and Islamic identity, inspiring Islamic
      world, as well as effective and constructive interaction in international
      relations. Enjoying health, welfare, food security, social security, equal
      opportunities, fair income distribution, strong family structure; to be away from
      poverty, corruption, and discrimination; and benefiting desirable living
      environment are also considered out of characteristics of Iranian society in that
      year. Strategic leadership towards perceived vision in each setting requires
      restrictive, complete and timely information. According to constitution of
      National Institute for Health Researches, law of the Fifth Development Plan of
      the country and characteristics of health policy making, necessity of designing a
      Health Observatory System (HOS) was felt. Some Principles for designing such
      system were formulated by taking following steps: reviewing experience in other
      countries, having local history of the HOS in mind, superior documents, analysis
      of current production and management of health information, taking the
      possibilities to run a HOS into account. Based on these principles, the protocol
      of HOS was outlined in 3 different stages of opinion poll of informed experts
      responsible for production on management of information, by using questionnaires
      and Focus Group Discussions. The protocol includes executive regulations, the
      list of health indicators, vocabulary and a calendar for periodic studies of the
      community health situation.

PMID- 23865023
TI  - Determining dimensions of iranians' individual social health: a qualitative
      approach.
AB  - BACKGROUND: Social health is important to be assessed as a dimension of health.
      The aim of study was to determine domains and sub-domains of individual social
      health of Iranians. METHODS: This study was carried out with a qualitative
      approach, using thematic content analysis. Twenty five experts participated in
      interviews, using individual semi-structured interviews between November 2010 and
      June 2011.This data supported with strong search. RESULTS: Two main areas
      extracted from these interviews including social support and social function. The
      social support domain contained seventeen sub-areas, including social support at
      the time of disease; disability; daily life issues, etc. And the social function
      as second domain contained twelve sub-areas, including: financial aids to others;
      emotionally aids to others; participating in social groups, etc. CONCLUSION: We
      developed a conceptual framework for social health in the individual level in
      Iranian population. It makes preparations for providing a valid and reliable
      measurement scale for social health in next studies and evidence-based policy
      making.

PMID- 23865024
TI  - Mortality causes in children 1-59 months in iran.
AB  - BACKGROUND: Mortality rate indicator for children under 5 years old is one of the
      important indicators in countries' development. Identifying the most common
      causes of mortality is one of the most important attempts to reduce mortality in
      children less than 5 years. The purpose of this study was to identify
      distribution of the mortality causes in Iranian children less than 5 years.
      METHODS: This cross-sectional study has been carried out based on the results of
      data from the Child Mortality Surveillance System since 2007 to 2008. To
      determine the causes of death questionnaires have been designed which include
      personal data of the deceased child, medical history, and information on
      procedures at the time of hospitalization or death. RESULTS: Of 5926 deaths on
      children under 5 years which the questionnaires were filled out, 63.2% were
      postneonatal deaths (1-11 month). Totally 60% of mortalities occurred in the
      rural areas and 52% of them had been among boys. The most common causes of
      mortality were the congenital and chromosomal abnormalities with 23.4%. The most
      incidences among diseases were respiratory system diseases. CONCLUSIONS: Carrying
      out more epidemiologic studies, providing health programs to control and prevent
      diseases with high incidences and delivering more specialized health facilities
      and services could be the proper strategies to reduce under 5 mortality rates in
      Iran.

PMID- 23865025
TI  - Counseling and Harm Reduction Centers for Vulnerable Women to HIV/AIDS in Iran.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) is a public health challenge
      facing both developing and developed nations. Although injecting drug use is even
      the main route of HIV transmission in Iran, sexual route is rising gradually.
      Vulnerable women have been considered as important bridging population for
      driving HIV epidemics. To increase the access to vulnerable women, in 2007, 5
      pilot centers were established in risky areas to deliver comprehensive services
      to women who themselves or their spouses are engaged in drug use, risky sexual
      behavior or have history of imprisonment. Management of Sexually Transmitted
      Infection, psychological counseling and harm reduction are provided by female
      staff. The aim of this study was to report the activities conducting in 2008.
      METHODS: Registered information was used to assess the demographic
      characteristic, HIV/ AIDS related risk factors and services delivered to clients.
      RESULTS: Till March 2008, 442 clients have been admitted. Most of them (36.2%)
      had 25-34 years old. 14.3% were illiterate and 31% were totally jobless. The most
      prevalent risk factors were risky sexual behavior (27.1%) and non-injecting drug
      use (23.2%). Injecting drug use was detected in 11.3% of attendees. Dividing
      clients according to marital status, risky sexual behavior was the main risk
      factor in unmarried (40.2%) and divorced (26.9%) but in married and widow ones,
      non-injecting drug use was the most (25.8% and 36.5% respectively). Harm
      reduction (40.5%) and counseling (36.6%) were the most delivered services.
      CONCLUSION: Since vulnerable women play a critical role to spread HIV-epidemic to
      general population, increasing centers provide more access to this population.

PMID- 23865026
TI  - What to do to promote mental health of the society.
AB  - BACKGROUND: According to the last existing documents, the prevalence rate of
      mental disorders is about 20% which is considered to be 14% of all country's
      burden of disease. In the fifth economical, social, and cultural development plan
      of the country in accordance with the 20 year vision, "healthy human being" and
      "comprehensive health" approaches and also improving of mental health indicators
      are emphasized. Aim of study was preparing national policy and interventions for
      promoting mental health. METHODS: Using secondary data, analytical review of
      country's mental health programs, recommendations of WHO, descriptive situation
      of mental health and its trend during the last decade were drafted and a group of
      experts and stakeholders was formed following a sound stakeholder's analysis.
      After three Focus Group Discussions (FGDs), main points of the meetings,
      influencing factors of present situation, and oncoming strategies were agreed
      upon. RESULTS: Based on different studies and the experts' opinions, the
      prevalence of mental disorders in the last decade has increased. Coverage of
      mental health programs in two last decades in the best could be equal to rural
      population. Urban areas have been deprived of these services. Analysis of mental
      health system of the country shows that internal environment is weak and the
      external one is concede to be in threat. Eight principal challenges in country's
      mental health are considered. CONCLUSION: Improving current situation requires
      increasing internal capacity of mental health system and developing inter
      sectoral cooperation. During next five years, the Ministry of Health, Iran should
      mainly focus on improving mental health services particularly in urban and peri
      urban areas, promoting mental health literacy of different groups and minimizing
      mental health risk factors.

PMID- 23865027
TI  - Urbanization and non-communicable risk factors in the capital city of 6 big
      provinces of iran.
AB  - BACKGROUND: The prevalence of non-communicable diseases such as hypertension and
      diabetes including obesity has increased over the past few years in Iran. The
      increase in these diseases has been associated with increased urbanization and
      lifestyle changes. The burden of non-communicable diseases (NCD) is increasing in
      low and middle-income countries. The aim of this report is to address the threat
      of NCDs in the capital city of 6 big provinces of Iran. METHODS: A community
      based cross sectional study was carried out between March 2010 to January 2011 in
      6 provinces' capital cities (Isfahan, Karaj, Mashad, Shiraz, Tabriz, and Tehran).
      Participants were men and women of 30 years and older who had been screened
      through the National Diabetes Prevention and Control Program. BMI, blood
      pressure, fasting blood glucose and lipids were measured. RESULTS: 439406 cases
      (60% female & 40% male) were studied. The prevalence of pre-diabetes (13%),
      diabetes (13%), hypercholesterolemia (14%), hypertension (11%), overweight (27%)
      and obesity (20%) was higher than expected. Only 35% of participants were
      healthy. CONCLUSION: This study reveals a high prevalence of NCDs in urban living
      population in those capital cities. It also shows that increasing urbanization
      may be an important threat to public health regarding NCDs especially in
      developing countries. It is crucial to implement a comprehensive NCD program
      (across the life time) in the health system with a strong collaboration with all
      stakeholders (governmental and non-governmental sector, academic, research
      centers and scientific associations) in the community (Multisectoral Approaches).

PMID- 23865028
TI  - Quality assurance program for molecular medicine laboratories.
AB  - BACKGROUND: Molecular diagnostic methods have played and continuing to have a
      critical role in clinical laboratories in recent years. Therefore,
      standardization is an evolutionary process that needs to be upgrade with
      increasing scientific knowledge, improvement of the instruments and techniques.
      The aim of this study was to design a quality assurance program in order to have
      similar conditions for all medical laboratories engaging with molecular tests.
      METHODS: We had to design a plan for all four elements; required space
      conditions, equipments, training, and basic guidelines. Necessary guidelines was
      prepared and confirmed by the launched specific committee at the Health Reference
      Laboratory. RESULTS: Several workshops were also held for medical laboratories
      directors and staffs, quality control manager of molecular companies, directors
      and nominees from universities. Accreditation of equipments and molecular
      material was followed parallel with rest of program. Now we are going to accredit
      medical laboratories and to evaluate the success of the program. CONCLUSION:
      Accreditation of medical laboratory will be succeeding if its basic elements are
      provided in advance. Professional practice guidelines, holding training and
      performing accreditation the molecular materials and equipments ensured us that
      laboratories are aware of best practices, proper interpretation, limitations of
      techniques, and technical issues. Now, active external auditing can improve the
      applied laboratory conditions toward the defined standard level.

PMID- 23865029
TI  - Challenges of implementing Iranian national laboratory standards.
AB  - After four years of publishing the Iranian National Laboratory Standard and
      following a strategic plan to implement its requirements, it was decided to
      review the taken actions, evaluating the achievements and the failures, as well
      as analyzing the gaps and planning the interventional activities to resolve the
      problems. A thorough evaluation revealed that the progress of implementation
      process varies considerably in different provinces, as well as in laboratories in
      different public and private sectors. Diversity and heterogeneousity of
      laboratories throughout the country is one of unresolvable problems. Although we
      encounter shortage of resources in the country, improper allocation or
      distribution of resources and budgets make the problems more complicated.
      Inadequacy of academic training in laboratory sciences has resulted in necessity
      of holding comprehensive post-graduate training courses. Revising academic
      curriculum of laboratory sciences could be mostly helpful, moreover there should
      be organized, training courses with pre-determined practical topics. providing
      specific technical guidelines, to clarify the required technical details could
      temporarily fill the training gaps of laboratory staff. Inadequate number of
      competent auditors was one of the difficulties in universities. Another important
      challenge returns to laboratory equipment, developing the national controlling
      system to manage the laboratory equipment in terms of quality and accessibility
      has been planned in RHL. At last cultural problems and resistance to change are
      main obstacles that have reduced the pace of standardization, it needs to
      rationalize the necessity of establishing laboratory standards for all
      stakeholders. 

PMID- 23865030
TI  - Dental Curriculum Revision in Iran: Dentists' Perspective on Achievement of
      Essential Competencies through National Curriculum.
AB  - BACKGROUND: Based on the current emphasis on competency-based education, as a
      part of need assessment phase of dental curriculum revision in Iran, in the
      present study the dental graduates' perspective concerning the minimum competency
      requirements for an Iranian general dentist has been investigated. METHODS: Based
      on the three available major competency documents in the literature a
      questionnaire was developed in which the participants were asked to indicate
      their opinion about the necessity of each of the 142 stated competencies for an
      Iranian general dentist (Yes/No), and to state the degree to which they believed
      the current curriculum covers each competency (Completely, Partially, Not at
      all). In an annual meeting in June 2008, the provincial chief dental managers
      were asked to distribute the questionnaires among general dentists in their
      province (10 questionnaires in each province). The managers posted back the
      completed questionnaires to the researchers. RESULTS: Of 300 questionnaires
      distributed in the 30 provinces of the country, 250 questionnaires (83%) were
      returned. While most of the participants considered the competencies as necessary
      for an Iranian dentist, less than 40% of the respondents believed that the
      graduates acquire the most required competencies of the profession during the
      current educational program. CONCLUSION: A necessity exists for curriculum
      revision. In addition to clinical skills, in this revision more emphasis also
      should be placed on the non-clinical part of the curriculum.

PMID- 23865031
TI  - Accreditation the Education Development Centers of Medical-Sciences Universities:
      Another Step toward Quality Improvement in Education.
AB  - BACKGROUND: In order to improve the quality of education in universities of
      medical sciences (UMS), and because of the key role of education development
      centers (EDCs), an accreditation scheme was developed to evaluate their
      performance. METHOD: A group of experts in the medical education field was
      selected based on pre-defined criteria by EDC of Ministry of Health and Medical
      education. The team, worked intensively for 6 months to develop a list of
      essential standards to assess the performance of EDCs. Having checked for the
      content validity of standards, clear and measurable indicators were created via
      consensus. Then, required information were collected from UMS EDCs; the first
      round of accreditation was carried out just to check the acceptability of this
      scheme, and make force universities to prepare themselves for the next factual
      round of accreditation. RESULTS: Five standards domains were developed as the
      conceptual framework for defining main categories of indicators. This included:
      governing and leadership, educational planning, faculty development, assessment
      and examination and research in education. Nearly all of UMS filled all required
      data forms precisely with minimum confusion which shows the practicality of this
      accreditation scheme. CONCLUSION: It seems that the UMS have enough interest to
      provide required information for this accreditation scheme. However, in order to
      receive promising results, most of universities have to work intensively in order
      to prepare minimum levels in all required standards. However, it seems that in
      long term, implementation of a valid accreditation scheme plays an important role
      in improvement of the quality of medical education around the country.

PMID- 23865032
TI  - The trend of governmental support from post-graduated Iranian students in medical
      fields to study abroad.
AB  - BACKGROUND: To explore the trend and composition of post-graduate Iranian
      students who received governmental scholarship during the last two decades.
      METHOD: Detailed information about the awarded scholarships and also about the
      number of post graduate students in clinical and basic sciences in domestic
      universities were collected from the related offices within the ministry of
      health and medical education and their trends were triangulated. RESULTS: A sharp
      drop was observed in the number of awarded scholarships, from 263 in 1992 to 46
      in 2009. In the beginning, almost all of scholarships fully supported students
      for a whole academic course; while in recent years most of scholarships supported
      students for a short fellowship or complementary course (more than 80%). Students
      studied in a wide range of colleges within 30 countries; more than 50% in Europe.
      Although one third of students studied in UK in the first years, only 4% of
      students selected this country in recent years. conversely, the number of
      scholarships to Germany and sweden have increased more than 10 and 3 times during
      this period. In parallel, the capacity of domestic universities for training of
      post-graduate students has been expanded dramatically. CONCLUSION: Although
      expanding post-graduate education has been one of the main strategic objectives
      of the ministry of health and medical education in last two decades, it was
      obtained using different approaches. By time, more attention was to expanding the
      capacities of Iranian universities, and choosing less but more targeted students
      to continue their studies abroad.

PMID- 23865033
TI  - Necessity of accreditation standards for quality assurance of medical basic
      sciences.
AB  - BACKGROUND: The present article reviews the significance of accreditation
      standards while emphasizing the necessity of implementation of such standards by
      basic medical science council, with an eye on such international standards as
      those published by WFME. This review article had to decide on the key words and
      expressions, data bases, to review relevant literature, review higher and medical
      education journals at GOOGLE, ELSEVIER, PUBMED, and such web sites as those of
      WFME and WMA's. Accreditation is a powerful leverage for institutional change and
      improvement and must be actively supported by academic and national health
      authorities worldwide. Considering the mission of the Basic Medical Science,
      Health and Post grad. Education, Ministry of Health and Medical Education,
      Tehran, Iran as accountable medical education, all specialists of the spectrum of
      disciplines agreed on the necessity of formulating the medical education
      standards for all disciplines of their interest. It is important that all efforts
      be joined in the endeavor to create effective and reliable instruments for
      quality assurance of Basic Medical Sciences Education.

PMID- 23865034
TI  - Determinants of catastrophic health expenditure in iran.
AB  - BACKGROUND: This study will provide detailed specification of those variables and
      determinants of unpredictable health expenditure in Iran, and the requirements to
      reduce extensive effects of the factors affecting households' payments for health
      and other goods and services inappropriately. METHOD: This study aims to identify
      measures of fair financing of health services and determinants of fair financing
      contribution, regarding the required share of households that prevents their
      catastrophic payments. In this regard, analysis of shares of households'
      expenditures on main groups of goods and services in urban and rural areas and in
      groups of deciles in the statistics from households' expenditure surveys was
      applied. RESULTS: The growth of spending in nominal values within the years 2002
      2008 was considerably high and the rate for out-of-pocket payments is nearly the
      same or greater than the rate for total health expenditure. In 2008, urban and
      rural households in average pay 6.4% and 6.35% of their total expenditure on
      health services. Finally three categories of determinants of unfair and
      catastrophic payments by households were recognized in terms of households' socio
      economic status, equality/inequality conditions of the distribution of risk of
      financing, and economic aspects of health expenditure distribution. CONCLUSION:
      While extending the total share of government and prepayment sources of financing
      health services are considered as the simplest policy for limiting out-of-pocket
      payments, indicators and policies introduced in this study could also be
      considered important and useful for the development of health sector and easing
      access to health services, irrespective of health financing fairness.

PMID- 23865035
TI  - Equality in Distribution of Human Resources: the Case of Iran's Ministry of
      Health and Medical Education.
AB  - BACKGROUND:  BACKGROUND: Equity in access to and utilization of health services
      is a common goal of policy-makers in most countries. The fair allocation of human
      resources is one of the dimensions of equity, which was evaluated in this study.
      METHODS: We evaluated the equity of human resources' distribution among Iran's
      medical science universities between 2005 and 2009 by inequality measures
      including Lorenze curve, Gini coefficient and Rabin hood indexes. RESULTS: In the
      distribution 60403 recruitment licenses among medical universities with 72456140
      covered populations, Gini coefficient was 0.167 and Robin Hood Index 0.11.
      CONCLUSIONS: Calculations indicated Recruitment licenses are equitably
      distributed in MOH&ME of Iran. However a portion of recruitment licenses should
      redistributed for achieving perfect equal distribution among all public medical
      universities of Iran.

PMID- 23865036
TI  - Allocation of health resources according to the type and size of Iranian
      governmental hospitals.
AB  - BACKGROUND: Due to consuming about 50%-80% of health resources, hospitals are the
      greatest and costly operational units in Iranian Health system. so allocation of
      resources specially human and space resources as the most expensive ones is
      really important for further controlling of costs, analysis of costs and making
      suitable policies for increasing the profitability and allocation of resources
      and improvement of quality. METHOD: This paper intends to describe and analyze
      any allocation of resources in 530 university hospitals in Iran. The final goal
      of this research is to provide a data bank according which there is a basis for
      more scientific budget allocation of state's hospitals from the size and type of
      application points of view. RESULTS: The relevant index of person to bed was 2.04
      for human resources. All hospitals more than 300 beds are located in benefiting
      areas from which 17 cases are educational and 2 cases are therapeutic. This is
      necessary to mention that the rate of management group forces to total personnel
      at deprived areas is about 2.5% more than benefiting areas. CONCLUSION: Because
      60-80% of hospital costs are applied for human forces, all managers of hospitals
      are obliged to revise their policies in attraction and employment of human force
      in order to benefit from such a valuable resource and prevent from expensive
      costs. So any employment of personnel should be based upon real needs of
      hospital.

PMID- 23865037
TI  - Islamic Republic of Iran's Health System: Achievements and Prospective.

PMID- 23865038
TI  - Effect of pupil size on optical quality parameters in astigmatic eyes using a
      double-pass instrument.
AB  - PURPOSE: To objectively determine the effects of pupil size on optical quality
      parameters in astigmatic eyes using a double-pass instrument. METHODS: We
      examined twenty-two eyes of 22 healthy volunteers (mean age  +/-  standard
      deviation, 27.1 +/- 2.8 years) who had no ophthalmic diseases other than
      refractive errors (manifest cylinder <= 0.25 diopters (D)). After we fully
      corrected cycloplegic refraction, we created with-the-rule astigmatism of 1, 2,
      and 3 diopters in these eyes and then quantitatively assessed the modulation
      transfer function (MTF) cutoff frequency and the Strehl2D ratio with 2-, 4-, and
      6-mm pupil sizes using the Optical Quality Analysis System. RESULTS: The MTF
      cutoff frequency and the Strehl2D ratio decreased significantly as the amount of
      astigmatism increased at each pupil size (P < 0.001 for 2, 4, and 6 mm, analysis
      of variance). They also decreased significantly with an increase in pupil size at
      each diopter of astigmatism (P < 0.001 for 0, 1, 2, and 3 D). Multiple
      comparisons demonstrated a significant difference between measurements made for a
      2-mm pupil and for a 6-mm pupil at each diopter of astigmatism (P < 0.001 for 0,
      1, 2, and 3 D, Dunnett test) and those made for a 4-mm pupil and for a 6-mm pupil
      at each diopter of astigmatism (P < 0.001 for 0 D, P < 0.05 1, 2, and 3 D).
      CONCLUSIONS: Eyes with larger pupils had lower optical quality even when they
      were astigmatic. It may be necessary to correct the preexisting astigmatism to
      acquire excellent visual performance, especially in astigmatic eyes with larger
      pupils.

PMID- 23865039
TI  - Investigating differences in health-related quality of life of Greeks and
      Albanian immigrants with the generic EQ-5D questionnaire.
AB  - BACKGROUND: Low socioeconomic status (SES) has been related by previous studies
      to low self-perceived HRQoL. Health is a major determinant of the society's
      welfare, and few studies have determined the relevant elements that contribute to
      health and quality of life in Greece. AIM: The aim of the study was to evaluate
      and test for differences in HRQoL of Greek and Albanian immigrant population
      according to ethnicity and their demographic and SES characteristics. METHODS:
      The study was conducted in a sample of 660 age-matched and gender-matched Greeks
      and Albanian immigrants. Moderate or severe decrease in HRQoL was assessed with
      the generic tool EQ-5D. Differences were statistically analyzed by t-test and
      ANOVA. Also, logistic and linear regression analyses were conducted for the
      dependent variables of the EQ-5D dimensions and VAS scores, respectively.
      RESULTS: The Albanian immigrants reported better self-perceived health than their
      Greek counterparts. Health problems increase moderately with age and lower SES
      and are slightly higher for women than for men. Urbanity and superior education
      in both Greeks and Albaniansareassociated with worse HRQoL. CONCLUSION: There are
      some structural and compositional differences in the self-perceived quality of
      life between the two ethnicities, as estimated by EQ-5D. The combined information
      presents to public health providers the relevant data to assess health policies
      according to health needs.

PMID- 23865040
TI  - Strategies to characterize fungal lipases for applications in medicine and dairy
      industry.
AB  - Lipases are water-soluble enzymes that act on insoluble substrates and catalyze
      the hydrolysis of long-chain triglycerides. Lipases play a vital role in the
      food, detergent, chemical, and pharmaceutical industries. In the past, fungal
      lipases gained significant attention in the industries due to their substrate
      specificity and stability under varied chemical and physical conditions. Fungal
      enzymes are extracellular in nature, and they can be extracted easily, which
      significantly reduces the cost and makes this source preferable over bacteria.
      Soil contaminated with spillage from the products of oil and dairy harbors fungal
      species, which have the potential to secrete lipases to degrade fats and oils.
      Herein, the strategies involved in the characterization of fungal lipases,
      capable of degrading fatty substances, are narrated with a focus on further
      applications. 

PMID- 23865041
TI  - Spectacle coverage and spectacles use among elderly population in residential
      care in the south Indian state of Andhra Pradesh.
AB  - BACKGROUND: There is limited research conducted on uncorrected refractive errors,
      presbyopia, and spectacles use among the elderly population in residential care
      in developing countries such as India. We conducted a cross-sectional study among
      elderly in residential care to assess the spectacle coverage and spectacles usage
      in the south Indian state of Andhra Pradesh. METHODS: All 524 residents in the 26
      "homes for aged" institutions in the district were enumerated. Eye examination
      was performed that included visual acuity (VA) assessment for distant and near
      vision. A questionnaire was used to collect information on spectacles use.
      RESULTS: 494/524 individuals were examined, 78% were women, and 72% had no
      education. The mean age of participants was 70 years. The spectacle coverage for
      refractive errors was 35.1% and 23.9% for presbyopia. The prevalence of current
      use and past use of spectacles was 38.5% (95% CI: 34.2-42.8; n = 190) and 17.2%
      (95% CI: 13.9-42.8), respectively. CONCLUSIONS: There is low spectacle coverage
      for both refractive errors and presbyopia among elderly individuals in
      residential care in the south Indian state of Andhra Pradesh. Appropriate service
      delivery systems should be developed to reach out this vulnerable group of
      seniors on a priority basis.

PMID- 23865042
TI  - Is neutrophil/lymphocyte ratio associated with subclinical inflammation and
      amyloidosis in patients with familial Mediterranean fever?
AB  - BACKGROUND: The purpose of the present study is to determine the association
      between neutrophil/lymphocyte ratio and both subclinical inflammation and
      amyloidosis in familial Mediterranean fever. METHODS: Ninety-four patients with
      familial Mediterranean fever and 60 healthy volunteers were included in the
      study. Of the patients, 12 had familial Mediterranean fever related amyloidosis.
      The neutrophil/lymphocyte ratio of the patients was obtained from the hematology
      laboratory archive. RESULTS: The neutrophil/lymphocyte ratio was significantly
      higher among persons with familial Mediterranean fever compared to healthy
      individuals (P < 0.0001). Also, neutrophil/lymphocyte ratio was significantly
      higher in patients with amyloidosis than in amyloidosis-free patients (P <
      0.0001). Since NLR was evaluated in nonamyloid and amyloid stages of the same
      patient population (type 1 phenotype), we obtained significant statistical
      differences (1.95 +/- 0.30 versus 2.64 +/- 0.48, P < 0.05, resp.). With the
      cutoff value of neutrophil/lymphocyte ratio >2.21 and AUC = 0.734 (P = 0.009), it
      was a reliable marker in predicting the development of amyloidosis. CONCLUSION:
      The neutrophil/lymphocyte ratio, an emerging marker of inflammation, is higher in
      patients with familial Mediterranean fever in attack-free periods. The
      neutrophil/lymphocyte ratio may be a useful marker in predicting the development
      of amyloidosis.

PMID- 23865043
TI  - Bovine papillomavirus in Brazil: detection of coinfection of unusual types by a
      PCR-RFLP method.
AB  - Bovine papillomavirus (BPV) is recognized as a causal agent of benign and
      malignant tumors in cattle. Thirteen types of BPV are currently characterized and
      classified into three distinct genera, associated with different pathological
      outcomes. The described BPV types as well as other putative ones have been
      demonstrated by molecular biology methods, mainly by the employment of
      degenerated PCR primers. Specifically, divergences in the nucleotide sequence of
      the L1 gene are useful for the identification and classification of new
      papillomavirus types. On the present work, a method based on the PCR-RFLP
      technique and DNA sequencing was evaluated as a screening tool, allowing for the
      detection of two relatively rare types of BPV in lesions samples from a six-year
      old Holstein dairy cow, chronically affected with cutaneous papillomatosis. These
      findings point to the dissemination of BPVs with unclear pathogenic potential,
      since two relatively rare, new described BPV types, which were first
      characterized in Japan, were also detected in Brazil. 

PMID- 23865045
TI  - Incidence of heterotopic ossification after surface and conventional total hip
      arthroplasty: a comparative study using anterolateral approach and indomethacin
      prophylaxis.
AB  - The incidence and severity of heterotopic ossification (HO) in two homogeneous
      groups of patients that received surface replacement arthroplasty (SRA) and
      conventional total hip arthroplasty (THA) were evaluated retrospectively. Thirty
      nine patients undergoing 42 hip resurfacing procedures and 41 primary cementless
      THAs through an anterolateral approach received a 10-day course of 150 mg/die of
      indomethacin postoperatively. The median surgical time was 190 minutes and 156
      minutes, respectively (P < 0.003). At a minimum 1-year followup, the development
      of HO was assessed on standard X-ray using Brooker grading. Ectopic bone
      formation was detected in five cases (11.9%, two Brooker grade I and three grade
      II) in the SRA group and in 14 hips (34.1%, 12 grade I and two grade II) treated
      with conventional THA, but the difference was not significant (P < 0.11). No
      clinically relevant periprosthetic ossification (Brooker III or IV) occurred in
      both groups. Although the difference was not statistically significant, the
      incidence of HO after SRA was lower than conventional THA. More extensive soft
      tissue trauma, bone debris, and longer operative time in hip resurfacing are not
      likely to be absolute risk factors for HO. Further investigations including
      larger patient populations are needed to confirm these findings.

PMID- 23865044
TI  - Recent advances in particulate matter and nanoparticle toxicology: a review of
      the in vivo and in vitro studies.
AB  - Epidemiological and clinical studies have linked exposure to particulate matter
      (PM) to adverse health effects, which may be registered as increased mortality
      and morbidity from various cardiopulmonary diseases. Despite the evidence
      relating PM to health effects, the physiological, cellular, and molecular
      mechanisms causing such effects are still not fully characterized. Two main
      approaches are used to elucidate the mechanisms of toxicity. One is the use of in
      vivo experimental models, where various effects of PM on respiratory,
      cardiovascular, and nervous systems can be evaluated. To more closely examine the
      molecular and cellular mechanisms behind the different physiological effects, the
      use of various in vitro models has proven to be valuable. In the present review,
      we discuss the current advances on the toxicology of particulate matter and
      nanoparticles based on these techniques. 

PMID- 23865046
TI  - Interference with RUNX1/ETO leukemogenic function by cell-penetrating peptides
      targeting the NHR2 oligomerization domain.
AB  - The leukemia-associated fusion protein RUNX1/ETO is generated by the chromosomal
      translocation t(8;21) which appears in about 12% of all de novo acute myeloid
      leukemias (AMLs). Essential for the oncogenic potential of RUNX1/ETO is the
      oligomerization of the chimeric fusion protein through the nervy homology region
      2 (NHR2) within ETO. In previous studies, we have shown that the intracellular
      expression of peptides containing the NHR2 domain inhibits RUNX1/ETO
      oligomerization, thereby preventing cell proliferation and inducing
      differentiation of RUNX1/ETO transformed cells. Here, we show that introduction
      of a recombinant TAT-NHR2 fusion polypeptide into the RUNX1/ETO growth-dependent
      myeloid cell line Kasumi-1 results in decreased cell proliferation and increased
      numbers of apoptotic cells. This effect was highly specific and mediated by
      binding the TAT-NHR2 peptide to ETO sequences, as TAT-polypeptides containing the
      oligomerization domain of BCR did not affect cell proliferation or apoptosis in
      Kasumi-1 cells. Thus, the selective interference with NHR2-mediated
      oligomerization by peptides represents a challenging but promising strategy for
      the inhibition of the leukemogenic potential of RUNX1/ETO in t(8;21)-positive
      leukemia. 

PMID- 23865048
TI  - Border malaria associated with multidrug resistance on Thailand-Myanmar and
      Thailand-Cambodia borders: transmission dynamic, vulnerability, and surveillance.
AB  - This systematic review elaborates the concepts and impacts of border malaria,
      particularly on the emergence and spread of Plasmodium falciparum and Plasmodium
      vivax multidrug resistance (MDR) malaria on Thailand-Myanmar and Thailand
      Cambodia borders. Border malaria encompasses any complex epidemiological settings
      of forest-related and forest fringe-related malaria, both regularly occurring in
      certain transmission areas and manifesting a trend of increased incidence in
      transmission prone areas along these borders, as the result of interconnections
      of human settlements and movement activities, cross-border population migrations,
      ecological changes, vector population dynamics, and multidrug resistance. For
      regional and global perspectives, this review analyzes and synthesizes the
      rationales pertaining to transmission dynamics and the vulnerabilities of border
      malaria that constrain surveillance and control of the world's most MDR
      falciparum and vivax malaria on these chaotic borders. 

PMID- 23865047
TI  - Antimicrobial resistance mechanisms among Campylobacter.
AB  - Campylobacter jejuni and Campylobacter coli are recognized as the most common
      causative agents of bacterial gastroenteritis in the world. Humans most often
      become infected by ingesting contaminated food, especially undercooked chicken,
      but also other sources of bacteria have been described. Campylobacteriosis is
      normally a self-limiting disease. Antimicrobial treatment is needed only in
      patients with more severe disease and in those who are immunologically
      compromised. The most common antimicrobial agents used in the treatment of
      Campylobacter infections are macrolides, such as erythromycin, and
      fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an
      alternative choice in the treatment of clinical campylobacteriosis but in
      practice are not often used. However, during the past few decades an increasing
      number of resistant Campylobacter isolates have developed resistance to
      fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides,
      and beta-lactams. Trends in antimicrobial resistance have shown a clear
      correlation between use of antibiotics in the veterinary medicine and animal
      production and resistant isolates of Campylobacter in humans. In this review, the
      patterns of emerging resistance to the antimicrobial agents useful in treatment
      of the disease are presented and the mechanisms of resistance to these drugs in
      Campylobacter are discussed. 

PMID- 23865049
TI  - Omega-3 fatty acids inhibit tumor growth in a rat model of bladder cancer.
AB  - Omega-3 (omega-3) fatty acids have been tested on prevention and treatment of
      several cancer types, but the efficacy on "in vivo" bladder cancer has not been
      analyzed yet. This study aimed at evaluating the chemopreventive efficacy of
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) mixture in an animal
      model of bladder cancer. Forty-four male Wistar rats were divided into 4 groups
      during a 20-week protocol: control; carcinogen-N-butyl-N-(4-hydroxybutyl)
      nitrosamine (BBN); omega-3 (DHA + EPA); and omega-3 + BBN. BBN and omega-3 were
      given during the initial 8 weeks. At week 20 blood and bladder were collected and
      checked for the presence of urothelium lesions and tumors, markers of
      inflammation, proliferation, and redox status. Incidence of bladder carcinoma
      was, control (0%), omega-3 (0%), BBN (65%), and omega-3 + BBN (62.5%). The omega
      3 + BBN group had no infiltrative tumors or carcinoma in situ, and tumor volume
      was significantly reduced compared to the BBN (0.9 +/- 0.1 mm(3) versus 112.5 +/-
      6.4 mm(3)). Also, it showed a reduced MDA/TAS ratio and BBN-induced serum CRP,
      TGF-beta1, and CD31 were prevented. In conclusion, omega-3 fatty acids inhibit
      the development of premalignant and malignant lesions in a rat model of bladder
      cancer, which might be due to anti-inflammatory, antioxidant, anti-proliferative,
      and anti-angiogenic properties.

PMID- 23865050
TI  - Secondary bacterial infections in patients with seasonal influenza A and pandemic
      H1N1.
AB  - The aim of the present study is to analyse the secondary bacterial infections in
      a large group of patients with seasonal influenza A and influenza A(H1N1) pdm09.
      Patients diagnosed with seasonal influenza A and influenza A(H1N1) pdm09 between
      2005 and 2009 were enrolled in the study. Data was retrieved from medical records
      and laboratory information systems (LIS). In total, 1094 patients with laboratory
      confirmed influenza were studied. There were 352 patients with seasonal influenza
      A and 742 patients with influenza A(H1N1) pdm09. The patients with influenza A
      were older and had higher comorbidity than patients with influenza A(H1N1) pdm09
      (P < 0.001 and P < 0.05, resp.). Hospital admission was higher in influenza A
      group (P = 0.01). In contrast, ICU admission was higher in patients with
      influenza A(H1N1) pdm09 than influenza A patients (P < 0.05). There were higher
      numbers of bacterial samples taken and culture positivity in patients with
      influenza A than patients with influenza A(H1N1) pdm09 (P < 0.0001 and P = 0.01,
      resp.). In both groups, the majority of the patients with positive bacterial
      cultures had underlying diseases. The present study shows that the patient
      characteristics and the frequency of secondary bacterial infections were
      different in patients with seasonal influenza A and in patients with influenza
      A(H1N1) pdm09.

PMID- 23865051
TI  - Enhanced removal of a pesticides mixture by single cultures and consortia of free
      and immobilized Streptomyces strains.
AB  - Pesticides are normally used to control specific pests and to increase the
      productivity in crops; as a result, soils are contaminated with mixtures of
      pesticides. In this work, the ability of Streptomyces strains (either as pure or
      mixed cultures) to remove pentachlorophenol and chlorpyrifos was studied. The
      antagonism among the strains and their tolerance to the toxic mixture was
      evaluated. Results revealed that the strains did not have any antagonistic
      effects and showed tolerance against the pesticides mixture. In fact, the growth
      of mixed cultures was significantly higher than in pure cultures. Moreover, a
      pure culture (Streptomyces sp. A5) and a quadruple culture had the highest
      pentachlorophenol removal percentages (10.6% and 10.1%, resp.), while
      Streptomyces sp. M7 presented the best chlorpyrifos removal (99.2%). Mixed
      culture of all Streptomyces spp. when assayed either as free or immobilized cells
      showed chlorpyrifos removal percentages of 40.17% and 71.05%, respectively, and
      for pentachlorophenol 5.24% and 14.72%, respectively, suggesting better removal
      of both pesticides by using immobilized cells. These results reveal that
      environments contaminated with mixtures of xenobiotics could be successfully
      cleaned up by using either free or immobilized cultures of Streptomyces, through
      in situ or ex situ remediation techniques. 

PMID- 23865052
TI  - Potential of chitinolytic Serratia marcescens strain JPP1 for biological control
      of Aspergillus parasiticus and aflatoxin.
AB  - Serratia marcescens strain JPP1 was isolated from peanut hulls in Huai'an city,
      Jiangsu Province, China. Its potential to inhibit the mycelial growth of
      Aspergillus parasiticus and the subsequent aflatoxin production was evaluated.
      The strain JPP1 could produce chitinase to degrade fungal cell walls, which was
      the main mechanism of strain JPP1 for biocontrol. Scanning electron microscopy of
      fungi treated with the crude chitinase revealed abnormal morphological changes.
      While the strain was grown in the peanut hulls-based medium, the chitinase
      activity reached 7.39 units. RT-PCR analysis showed that the crude chitinase
      repressed the transcription of genes involved in the aflatoxin gene cluster, such
      as aflR, aflC (pksL1), and aflO (dmtA) genes. By visual agar plate assay and tip
      culture method, the strain JPP1 exhibited remarkable inhibitory effect on mycelia
      growth (antifungal ratio >95%) and subsequent aflatoxin production
      (antiaflatoxigenic ratio >98%). An in vitro assay with seed coating agent of
      bacterial suspension showed that strain JPP1 effectively reduced fungal growth
      and subsequent aflatoxin production on peanut seeds, and its antagonistic effect
      was superior to the common agricultural fungicide of carbendazim. These
      characteristics suggest that S. marcescens JPP1 strain could potentially be
      utilized for the biological control of phytopathogenic fungi and aflatoxin in
      Chinese peanut main producing areas.

PMID- 23865053
TI  - Effect of fluorometholone/tetrahydrozoline fixed combination on conjunctival
      autograft morphology after primary pterygium excision.
AB  - PURPOSE: To evaluate the effect of a fluorometholone/tetrahydrozoline fixed
      combination on conjunctival graft morphology after primary pterygium excision.
      METHODS: The patients who underwent pterygium excision with conjunctival
      autograft transplantation were randomized into three groups based on
      postoperative medications as the fluorometholone/tetrahydrozoline group,
      fluorometholone group, and dexamethasone group. Conjunctival graft thickness was
      measured with anterior segment optical coherence tomography. The conjunctival
      graft hyperemia was evaluated using a high definition external camera. RESULTS:
      The mean graft thickness was significantly lower in the
      fluorometholone/tetrahydrozoline group compared with fluorometholone and
      dexamethasone groups at 2 weeks (P = 0.002 and P = 0.012, resp.) and at 1 month
      after surgery (P = 0.003 and P = 0.013, resp.). The conjunctival hyperemia score
      was significantly lower in the fluorometholone/tetrahydrozoline group compared
      with fluorometholone and dexamethasone groups at 2 weeks (P = 0.000 and P =
      0.000, resp.) and at 1 month (P = 0.039 and P = 0.040, resp.). The graft
      thickness and conjunctival hyperemia score were similar among the groups at 1
      week and 3 months (P > 0.05). CONCLUSION: The findings of the present study
      revealed that treatment with the fluorometholone/tetrahydrozoline fixed
      combination may be helpful to decrease graft edema and to achieve better cosmetic
      appearance at 2 weeks and 1 month after pterygium excision.

PMID- 23865054
TI  - Microalbuminuria and glomerular filtration rate in paediatric visceral
      leishmaniasis.
AB  - Visceral leishmaniasis, caused by Leishmania donovani, is a serious form of
      leishmaniasis and fatal if untreated. Nearly half of the VL cases are children.
      There are very few studies of renal function in pediatric visceral leishmaniasis.
      The aim of this study was to evaluate renal dysfunction by studying glomerular
      filtration rate (GFR), microalbuminuria, and microscopic examination of urine.
      Laboratory analysis was performed on blood and urine samples of 40
      parasitologically confirmed pediatric VL cases. Laboratory data of urine
      examination showed albuminuria in 10% (4/40), white blood cells in 20% (8/40),
      hematuria in 10% (4/40), microalbuminuria in 37.5% (15/40), and decreased GFR in
      27.5% (11/40). Renal involvement was manifested in most of the pediatric VL
      cases. These findings may help clinicians in decision making for safe and
      suitable antileishmanial treatment particularly in childhood VL. 

PMID- 23865056
TI  - Addressing the question of disorder-specific risk factors of internet addiction:
      a comparison of personality traits in patients with addictive behaviors and
      comorbid internet addiction.
AB  - Uncontrolled use of the internet has been reported to affect the lives of some
      users in a negative way. According to epidemiological studies, about 1% of the
      general population is showing signs of internet addiction. Since internet
      addiction is becoming a growing health concern, research on potential risk
      factors is becoming more important in order to develop strategies for prevention
      and to adopt therapeutic treatment. Although there are some studies investigating
      personality traits in internet addiction, most of these studies are based on
      samples of healthy subjects. In this research project, we compared personality
      profiles of a sample of patients in different rehabilitation centers. 70 patients
      with an addiction disorder that additionally met the criteria for internet
      addiction were compared to 48 patients suffering from alcohol dependence. Besides
      Big Five personality traits, we also assessed depressive symptoms. It was shown
      that patients with comorbid internet addiction can be discriminated from other
      patients by higher neuroticism and lower extraversion as well as lower
      conscientiousness. After controlling for depressive symptoms, lower
      conscientiousness especially turned out to be a disorder-specific risk factor. As
      internet addiction is related to unique patterns of personality traits and can be
      discriminated from alcohol dependence, treatment approaches are needed that meet
      the specific requirements of patients with internet addiction. 

PMID- 23865057
TI  - Prevalence and genetic variability in capsid L1 gene of rare human
      papillomaviruses (HPV) found in cervical lesions of women from North-East Brazil.
AB  - The aim of this study was to examine the prevalence and genetic variability of
      the capsid L1 gene of rare HPV genotypes that were found in the cervical lesions
      of women from North-East Brazil. A total number of 263 patients were included in
      this study. HPV detection was performed using PCR followed by direct sequencing
      of MY09/11, as well as type-specific PCR to detect the Alpha-9 species. Epitope
      prediction was performed to determine whether or not the genetic variants are
      inserted in B-cell and T-cell epitopes. The prevalence of rare HPV types in
      cervical lesions was found to be 9.47%. The rare HPV genotypes that were detected
      were HPV-53, 54, 56, 61, 62, 66, 70, and 81. The genetic variability in the L1
      gene of rare HPV types involved thirty nucleotide changes, eight of which were
      detected for the first time in this study. Moreover, some of these variants are
      embedded in B-cell or T-cell epitope regions. The results of this research
      suggest that rare HPV types might be involved in cervical lesions and some of
      these variants can be found in B-cell and T-cell epitopes. Data on the prevalence
      and variability of rare HPV types will assist in clarifying the role of these
      viruses in carcinogenesis. 

PMID- 23865058
TI  - Chitosan combined with poly-L-arginine as efficient, safe, and serum-insensitive
      vehicle with RNase protection ability for siRNA delivery.
AB  - Chitosan (CS) combined with poly-L-arginine (PLA) was formulated and evaluated
      for its performance to deliver siRNA to HeLa cells expressing enhanced green
      fluorescent protein (EGFP). Compared with the formulations using single polymer
      in which the polyplexes were completely formed at the weight ratio of >20 : 1 for
      CS/siRNA or 1 : 1 for PLA/siRNA, the combination of CS and PLA could reduce the
      amounts of the polymers required for the complete complexation with siRNA,
      thereby forming positively charged, nanosized polyplex at the weight ratio of
      CS/PLA/siRNA of 5 : 0.5: 1. In addition, while the transfection efficiency of
      CS/siRNA and PLA/siRNA was very low at physiological pH (7.4), CS/PLA/siRNA at
      the optimal weight ratio of 5 : 0.5 : 1 satisfactorily silenced the endogenous
      EGFP gene at pH 7.4 as well as at pH 6.4 without the deterrent effect from serum.
      The combined polymers could protect siRNA from RNase degradation over a period of
      at least 6 h. Furthermore, MTT assay results demonstrated that CS/PLA/siRNA
      complexes showed acceptably low cytotoxicity with 75% cell viability. Therefore,
      CS combined with PLA is easy to prepare, safe, and promising for use as an
      efficient siRNA delivery vehicle.

PMID- 23865055
TI  - Nutrition and the risk of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that
      accounts for the major cause of dementia, and the increasing worldwide prevalence
      of AD is a major public health concern. Increasing epidemiological studies
      suggest that diet and nutrition might be important modifiable risk factors for
      AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and
      polyunsaturated fatty acids are beneficial to AD, and consumptions of fish,
      fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD.
      However, many of the results from randomized controlled trials are contradictory
      to that of epidemiological studies. Dietary patterns summarizing an overall diet
      are gaining momentum in recent years. Adherence to a healthy diet, the Japanese
      diet, and the Mediterranean diet is associated with a lower risk of AD. This
      paper will focus on the evidence linking many nutrients, foods, and dietary
      patterns to AD. 

PMID- 23865060
TI  - Mean 5-year clinical and radiographic outcomes of cementless total hip
      arthroplasty in patients under the age of 30.
AB  - We performed a retrospective review of 40 consecutive modern cementless THAs with
      65-month mean followup in 34 patients under the age of 30 primarily for diagnoses
      other than inflammatory arthritis. We found acceptable functional improvement and
      radiographic outcomes at mean 5-year followup. We found a high transfusion rate,
      dislocation rate (10%), and midterm overall aseptic revision rate (17%). Twenty
      eight (67.5%) of hips in this series were metal on metal, with a large percentage
      of aseptic revisions related to metallosis (57%). When revisions due to
      metallosis were excluded, the aseptic revision rate was 7.5%. The high prevalence
      of prior pediatric hip surgery in these patients (50%) may predispose to
      increased technical difficulty resulting in increased complications and higher
      revision rates. Although our revision rate was high in these young patients, it
      is favorable compared to older techniques and consistent with the limited data
      available with modern cementless techniques in patients of similar age.
      Cementless THA with modern designs remains a viable option for the treatment of
      arthritis in the young patient.

PMID- 23865059
TI  - Intraperitoneal exposure to nano/microparticles of fullerene (C60) increases
      acetylcholinesterase activity and lipid peroxidation in adult zebrafish (Danio
      rerio) brain.
AB  - Even though technologies involving nano/microparticles have great potential, it
      is crucial to determine possible toxicity of these technological products before
      extensive use. Fullerenes C60 are nanomaterials with unique physicochemical and
      biological properties that are important for the development of many
      technological applications. The aim of this study was to evaluate the
      consequences of nonphotoexcited fullerene C60 exposure in brain
      acetylcholinesterase expression and activity, antioxidant responses, and
      oxidative damage using adult zebrafish as an animal model. None of the doses
      tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and
      oxidative damage when zebrafish were exposed to nonphotoexcited C60
      nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to
      the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented
      lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of
      brain AChE activity was neither related to the transcriptional control (RT-qPCR
      analysis) nor to the direct action of nonphotoexcited C60 nano/microparticles on
      the protein (in vitro results) but probably involved a posttranscriptional or
      posttranslational modulation of this enzymatic activity. Taken together these
      findings provided further evidence of toxic effects on brain after C60 exposure.

PMID- 23865061
TI  - Dengue in the United States of America: a worsening scenario?
AB  - Dengue is a febrile illness caused by any of the four dengue virus types (DENV-1
      to -4, genus Flavivirus, family Flaviviridae) mainly transmitted by the mosquito
      Aedes aegypti. DENV can be transmitted by blood transfusion. Dengue has been
      historically present in the continental United States (US), in the state of
      Hawaii, and in the US insular territories in the Caribbean and the Pacific.
      During the second half of the 20th century, most of the cases reported in the US
      were imported cases brought to the country by travelers. Since 2009, cases of
      autochthonous dengue have been recognized in the state of Florida after 75 years
      of absence, followed by intensification of transmission in endemic places
      including the US territories of US Virgin Islands and Puerto Rico, which
      experienced a large dengue epidemic in 2010. The widespread distribution of
      dengue mosquito vectors, deficient mosquito control measures and increased
      frequency of DENV-infected visitors to the US coming from dengue-endemic
      locations or places experiencing epidemics appear to be jointly responsible for
      the emergence and reemergence of dengue in the US and its territories. 

PMID- 23865063
TI  - Coefficient of energy balance: effective tool for early differential diagnosis of
      CNS diseases.
AB  - Urgent examination of cerebrospinal fluid (CSF) provides immediate important
      information about the character of central nervous system (CNS) impairment.
      Although this examination includes energy parameters such as glucose and lactate
      concentrations, it does not commonly use Coefficient of Energy Balance (CEB). In
      this study, we focused on CEB because it enables more exact assessment of actual
      energy state in the CSF compartment than glucose and lactate alone. CEB informs
      about the actual functioning condition of present cells, and it does not require
      any other analysis or costs. Using Kruskal-Wallis ANOVA, we examined a large CSF
      sample (n = 8183) and we compared CEB values among groups with different
      cytological syndromes. We found a statistically significant difference of CEB
      between the group with granulocyte pleocytosis and the control group. These
      results indicate a high degree of anaerobic metabolism caused by the oxidative
      burst of neutrophils. Similarly, we found a statistically significant difference
      of CEB between the control group and groups with tumorous oligocytosis plus
      pleocytosis and monocyte pleocytosis. This difference can be attributed to the
      oxidative burst of macrophages. Our findings suggest that CEB combined with CSF
      cytology has a great importance for diagnosis, differential diagnosis, and early
      therapy of CNS diseases. 

PMID- 23865064
TI  - Interinstitutional variation of caesarean delivery rates according to indications
      in selected obstetric populations: a prospective multicenter study.
AB  - The aim of the study was to identify which groups of women contribute to
      interinstitutional variation of caesarean delivery (CD) rates and which are the
      reasons for this variation. In this regard, 15,726 deliveries from 11 regional
      centers were evaluated using the 10-group classification system. Standardized
      indications for CD in each group were used. Spearman's correlation coefficient
      was used to calculate (1) relationship between institutional CD rates and
      relative sizes/CD rates in each of the ten groups/centers; (2) correlation
      between institutional CD rates and indications for CD in each of the ten
      groups/centers. Overall CD rates correlated with both CD rates in spontaneous and
      induced labouring nulliparous women with a single cephalic pregnancy at term (P =
      0.005). Variation of CD rates was also dependent on relative size and CD rates in
      multiparous women with previous CD, single cephalic pregnancy at term (P <
      0.001). As for the indications, "cardiotocographic anomalies" and "failure to
      progress" in the group of nulliparous women in spontaneous labour and "one
      previous CD" in multiparous women previous CD correlated significantly with
      institutional CD rates (P = 0.021, P = 0.005, and P < 0.001, resp.). These
      results supported the conclusion that only selected indications in specific
      obstetric groups accounted for interinstitutional variation of CD rates. 

PMID- 23865065
TI  - Predicting the DPP-IV inhibitory activity pIC50 based on their physicochemical
      properties.
AB  - The second development program developed in this work was introduced to obtain
      physicochemical properties of DPP-IV inhibitors. Based on the computation of
      molecular descriptors, a two-stage feature selection method called mRMR-BFS
      (minimum redundancy maximum relevance-backward feature selection) was adopted.
      Then, the support vector regression (SVR) was used in the establishment of the
      model to map DPP-IV inhibitors to their corresponding inhibitory activity
      possible. The squared correlation coefficient for the training set of LOOCV and
      the test set are 0.815 and 0.884, respectively. An online server for predicting
      inhibitory activity pIC50 of the DPP-IV inhibitors as described in this paper has
      been given in the introduction.

PMID- 23865062
TI  - The role of cytidine deaminases on innate immune responses against human viral
      infections.
AB  - The APOBEC family of proteins comprises deaminase enzymes that edit DNA and/or
      RNA sequences. The APOBEC3 subgroup plays an important role on the innate immune
      system, acting on host defense against exogenous viruses and endogenous
      retroelements. The role of APOBEC3 proteins in the inhibition of viral infection
      was firstly described for HIV-1. However, in the past few years many studies have
      also shown evidence of APOBEC3 action on other viruses associated with human
      diseases, including HTLV, HCV, HBV, HPV, HSV-1, and EBV. APOBEC3 inhibits these
      viruses through a series of editing-dependent and independent mechanisms. Many
      viruses have evolved mechanisms to counteract APOBEC effects, and strategies that
      enhance APOBEC3 activity constitute a new approach for antiviral drug
      development. On the other hand, novel evidence that editing by APOBEC3
      constitutes a source for viral genetic diversification and evolution has emerged.
      Furthermore, a possible role in cancer development has been shown for these host
      enzymes. Therefore, understanding the role of deaminases on the immune response
      against infectious agents, as well as their role in human disease, has become
      pivotal. This review summarizes the state-of-the-art knowledge of the impact of
      APOBEC enzymes on human viruses of distinct families and harboring disparate
      replication strategies. 

PMID- 23865066
TI  - Carotid artery segmentation in ultrasound images and measurement of intima-media
      thickness.
AB  - BACKGROUND: The segmentation of the common carotid artery (CCA) wall is
      imperative for the determination of the intima-media thickness (IMT) on B-mode
      ultrasound (US) images. The IMT is considered an important indicator in the
      evaluation of the risk for the development of atherosclerosis. In this paper,
      authors have discussed the relevance of measurements in clinical practices and
      the challenges that one has to face while approaching the segmentation of carotid
      artery on ultrasound images. The paper presents an overall review of commonly
      used methods for the CCA segmentation and IMT measurement along with the
      different performance metrics that have been proposed and used for performance
      validation. Summary and future directions are given in the conclusion.

PMID- 23865067
TI  - Assessment of hemodynamics in a rat model of liver cirrhosis with precancerous
      lesions using multislice spiral CT perfusion imaging.
AB  - RATIONALE AND OBJECTIVES: To develop an optimal scanning protocol for multislice
      spiral CT perfusion (CTP) imaging to evaluate hemodynamic changes in liver
      cirrhosis with diethylnitrosamine- (DEN-) induced precancerous lesions. MATERIALS
      AND METHODS: Male Wistar rats were randomly divided into the control group (n =
      80) and the precancerous liver cirrhosis group (n = 40). The control group
      received saline injection and the liver cirrhosis group received 50 mg/kg DEN
      i.p. twice a week for 12 weeks. All animals underwent plain CT scanning, CTP, and
      contrast-enhanced CT scanning. Scanning parameters were optimized by adjusting
      the diatrizoate concentration, the flow rate, and the delivery time. The
      hemodynamics of both groups was further compared using optimized multislice
      spiral CTP imaging. RESULTS: High-quality CTP images were obtained with following
      parameters: 150 kV; 150 mAs; 5 mm thickness, 5 mm interval; pitch, 1; matrix, 512
      * 512; and FOV, 9.6 cm. Compared to the control group, the liver cirrhosis group
      had a significantly increased value of the hepatic arterial fraction and the
      hepatic artery perfusion (P < 0.05) but significantly decreased hepatic portal
      perfusion and mean transit time (P < 0.05). CONCLUSION: Multislice spiral CTP
      imaging can be used to evaluate the hemodynamic changes in the rat model of liver
      cirrhosis with precancerous lesions.

PMID- 23865068
TI  - Remarkable anti-trichomonas vaginalis activity of plants traditionally used by
      the Mbya-Guarani indigenous group in Brazil.
AB  - Trichomonas vaginalis, a flagellate protozoan, is the causative agent of
      trichomonosis, the most common nonviral sexually transmitted disease worldwide.
      Taking into account the increased prevalence of metronidazole-resistant isolates,
      alternative drugs are essential for the successful treatment. Natural products
      are the source of most new drugs, and popular wisdom about the use of medicinal
      plants is a powerful tool in this search. In this study, the activity of 10
      medicinal plants extensively used in daily life by Mbya-Guarani indigenous group
      was evaluated against seven different T. vaginalis isolates. Among the aqueous
      extracts tested, Verbena sp. (Guachu ka'a in Mbya-Guarani language) and
      Campomanesia xanthocarpa (Guavira in Mbya-Guarani language) showed the highest
      activity against T. vaginalis with MIC value of 4.0 mg/mL reaching 100% of
      efficacy against the parasite. The kinetic growth assays showed that the extracts
      promoted complete growth abolishment after 4 h of incubation. In addition, the
      extracts tested did not promote a significant hemolytic activity against human
      erythrocytes. Our results show for the first time the potential activity of
      Verbena sp. and C. xanthocarpa against T. vaginalis. In addition, this study
      demonstrates that indigenous knowledge is an important source of new prototype
      antiprotozoal agents. 

PMID- 23865069
TI  - Lower lid reconstruction utilizing auricular conchal chondral-perichondral tissue
      in patients with neoplastic lesions.
AB  - PURPOSE: To assess surgical outcomes of lower lid reconstruction surgery using
      auricular conchal tissue. METHODS: This prospective study included 20 patients
      that underwent reconstructive lower lid surgery using autologous auricle chondral
      perichondral graft tissue. Auricle tissue was used to provide adequate support
      and protection with similar conjunctiva tarsal structures on overlying soft
      tissues in patients with pathologic inferior lid tissue loss requiring
      reconstructive surgery. Biopsies with histopathology and cytology analysis were
      taken after 1 year. Cytology analysis using CK19 was used to confirm newly formed
      conjunctiva overlying the graft. RESULTS: All patients showed no graft rejection.
      Surgical outcomes were generally good, with minimal or no ocular complications.
      16 of 20 patients had excellent results, showing good lid symmetry and esthetics,
      minimal auricular discomfort, patient satisfaction and proper lid function.
      Surgical outcomes were highly dependent on proper post-op conjunctiva formation.
      All patients were positive for CK19, thus indicating proper conjunctiva tissue
      formation. CONCLUSIONS: Lower lid reconstruction surgery using auricular chondral
      perichondral conchal tissue is a good alternative in patients with neoplastic
      lesions. Autologous chondral-perichondral tissue provides good functional and
      mechanical support in the reconstructed lid, thus reducing the risks of ectropion
      and corneal exposure and ensuring a protected ocular surface.

PMID- 23865070
TI  - Reproducibility of NMR analysis of urine samples: impact of sample preparation,
      storage conditions, and animal health status.
AB  - INTRODUCTION: Spectroscopic analysis of urine samples from laboratory animals can
      be used to predict the efficacy and side effects of drugs. This employs methods
      combining (1)H NMR spectroscopy with quantification of biomarkers or with
      multivariate data analysis. The most critical steps in data evaluation are
      analytical reproducibility of NMR data (collection, storage, and processing) and
      the health status of the animals, which may influence urine pH and osmolarity.
      METHODS: We treated rats with a solvent, a diuretic, or a nephrotoxicant and
      collected urine samples. Samples were titrated to pH 3 to 9, or salt
      concentrations increased up to 20-fold. The effects of storage conditions and
      freeze-thaw cycles were monitored. Selected metabolites and multivariate data
      analysis were evaluated after (1)H NMR spectroscopy. RESULTS: We showed that
      variation of pH from 3 to 9 and increases in osmolarity up to 6-fold had no
      effect on the quantification of the metabolites or on multivariate data analysis.
      Storage led to changes after 14 days at 4 degrees C or after 12 months at -20
      degrees C, independent of sample composition. Multiple freeze-thaw cycles did not
      affect data analysis. CONCLUSION: Reproducibility of NMR measurements is not
      dependent on sample composition under physiological or pathological conditions.

PMID- 23865071
TI  - Effects of community-based cardiac rehabilitation on body composition and
      physical function in individuals with stable coronary artery disease: 1.6-year
      followup.
AB  - OBJECTIVE: To examine long-term changes in physical function and body composition
      in coronary artery disease (CAD) patients participating in ongoing community
      based cardiac rehabilitation (CR). DESIGN: Thirty-four individuals (69.7 +/- 8.2
      years; 79% men) participated in this longitudinal observational study. Baseline
      and follow-up assessments included incremental shuttle walk, short physical
      performance battery, handgrip strength, chair stands, body composition, last year
      physical activity, and CR attendance. RESULTS: Participants attended 38.5 +/-
      30.3% sessions during 1.6 +/- 0.2 year followup. A significant increase in 30
      second chair stands (17.0 +/- 4.7 to 19.6 +/- 6.4, P < 0.001), body weight (75.8
      +/- 11.1 to 77.2 +/- 12.1 kg, P = 0.001), and body fat (27.0 +/- 9.5 to 29.1 +/-
      9.6%, P < 0.001) and a decline in handgrip strength (36.4 +/- 9.4 to 33.0 +/-
      10.6 kg.f, P < 0.001) and muscle mass (40.8 +/- 5.6 to 39.3 +/- 5.8%, P < 0.001)
      were observed during followup. There was no significant change in shuttle walk
      duration. CR attendance was not correlated to observed changes. CONCLUSIONS:
      Elderly CAD patients participating in a maintenance CR program improve lower-body
      muscle strength but experience a decline in handgrip strength and unfavourable
      changes in body composition, irrespective of CR attendance.

PMID- 23865072
TI  - Detergent-enzymatic decellularization of swine blood vessels: insight on
      mechanical properties for vascular tissue engineering.
AB  - Small caliber vessels substitutes still remain an unmet clinical need; few
      autologous substitutes are available, while synthetic grafts show insufficient
      patency in the long term. Decellularization is the complete removal of all
      cellular and nuclear matters from a tissue while leaving a preserved
      extracellular matrix representing a promising tool for the generation of
      acellular scaffolds for tissue engineering, already used for various tissues with
      positive outcomes. The aim of this work is to investigate the effect of a
      detergent-enzymatic decellularization protocol on swine arteries in terms of cell
      removal, extracellular matrix preservation, and mechanical properties.
      Furthermore, the effect of storage at -80 degrees C on the mechanical properties
      of the tissue is evaluated. Swine arteries were harvested, frozen, and
      decellularized; histological analysis revealed complete cell removal and
      preserved extracellular matrix. Furthermore, the residual DNA content in
      decellularized tissues was far low compared to native one. Mechanical testings
      were performed on native, defrozen, and decellularized tissues; no statistically
      significant differences were reported for Young's modulus, ultimate stress,
      compliance, burst pressure, and suture retention strength, while ultimate strain
      and stress relaxation of decellularized vessels were significantly different from
      the native ones. Considering the overall results, the process was confirmed to be
      suitable for the generation of acellular scaffolds for vascular tissue
      engineering.

PMID- 23865073
TI  - A simple assay to screen antimicrobial compounds potentiating the activity of
      current antibiotics.
AB  - Antibiotic resistance continues to pose a significant problem in the management
      of bacterial infections, despite advances in antimicrobial chemotherapy and
      supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform
      assay to screen antimicrobial compounds from natural products or synthetic
      chemical libraries for their potential to work in tandem with the available
      antibiotics against multiple drug-resistant bacteria. The aqueous extract of
      Juglans regia tree bark was tested against representative multiple drug-resistant
      bacteria in the aforementioned assay to determine whether it potentiates the
      activity of selected antibiotics. The aqueous extract of J. regia bark was added
      to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria,
      Salmonella typhi or enteropathogenic E. coli. Next, filter paper discs
      impregnated with different classes of antibiotics were placed on the agar
      surface. Bacteria incubated with extract or antibiotics alone were used as
      controls. The results showed a significant increase (>30%) in the zone of
      inhibition around the aztreonam, cefuroxime, and ampicillin discs compared with
      bacteria incubated with the antibiotics/extract alone. In conclusion, our assay
      is able to detect either synergistic or additive action of J. regia extract
      against multiple drug-resistant bacteria when tested with a range of antibiotics.

PMID- 23865074
TI  - Cardiovascular profile of xanthelasma palpebrarum.
AB  - Xanthelasma palpebrarum (XP) are yellow plaques that occur most commonly near the
      inner canthus of the eyelid and are often associated with atherosclerosis,
      dyslipidemia, and coronary artery disease. This study was planned to address the
      issue of associated cardiovascular morbidity in xanthelasma patients attending
      our cardiac clinic. MATERIALS AND METHODS: A total of 61 patients were detected
      to be having xanthelasma and constituted the study group. The control group
      constituted of 130 apparently normal individuals. Each patient underwent detailed
      history, examination, and investigations. RESULTS AND DISCUSSION: The most
      prevalent age group was 40 to 60 years. Males outnumbered females. A percentage
      of 39.3% of cases had concomitant nicotine addiction. Dyslipidemia was present in
      60% of cases, hypertension in 37.7%, prehypertension in 8.77%, diabetes mellitus
      in 18.03%, and prediabetes in 26.3%. Smokers and obese patients with xanthelasma
      had a higher prevalence of hypertension. Coronary artery disease (CAD) was found
      in 6.56% of XP cases. The waist circumference and diastolic blood pressures were
      significantly higher in XP patients. CONCLUSION: A significant number of cases of
      xanthelasma palpebrarum are combined with smoking, central obesity, hypertension,
      diabetes mellitus, and dyslipidemia which are the major risk factors for CAD.
      Efforts should be made to rule out the same in high-risk xanthelasma subjects.

PMID- 23865075
TI  - Kidney dosimetry in 177Lu and 90Y peptide receptor radionuclide therapy:
      influence of image timing, time-activity integration method, and risk factors.
AB  - Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans
      to extrapolate the peptide kinetics, and it is considered time and resource
      consuming. We investigated the most adequate timing for imaging and time-activity
      interpolating curve, as well as the performance of a simplified dosimetry, by
      means of just 1-2 scans. Finally the influence of risk factors and of the peptide
      (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with
      (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6
      hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was
      calculated with our simplified method, as well as the ones most used in the
      clinic, that is, trapezoids, monoexponential, and biexponential functions. The
      same was done skipping the 6 h and the 3 d points. We found that data should be
      collected until 100 h for (177)Lu therapy and 70 h for (90)Y therapy, otherwise
      the dose calculation is strongly influenced by the curve interpolating the data
      and should be carefully chosen. Risk factors (hypertension, diabetes) cause a
      rather statistically significant 20% increase in dose (t-test, P < 0.10), with
      DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).

PMID- 23865076
TI  - Nanocarriers for diagnosis and targeting of breast cancer.
AB  - Breast cancer nanotherapeutics is consistently progressing and being used to
      remove the various limitations of conventional method available for the diagnosis
      and treatment of breast cancer. Nanoparticles provide an interdisciplinary area
      for research in imaging, diagnosis, and targeting of breast cancer. With advanced
      physicochemical properties and better bioavailability, they show prolonged blood
      circulation with efficient tumor targeting. Passive targeting mechanisms by using
      leaky vasculature, tumor microenvironment, or direct local application and active
      targeting approaches using receptor antibody, amplification in the ability of
      nanoparticles to target specific tumor can be achieved. Nanoparticles are able to
      reduce cytotoxic effect of the active anticancer drugs by increasing cancer cell
      targeting in comparison to conventional formulations. Various nanoparticles-based
      formulations are in the preclinical and clinical stages of development; among
      them, polymeric drug micelles, liposomes, dendrimer, carbon nanotubes, and
      nanorods are the most common. In this review, we have discussed the role of
      nanoparticles with respect to oncology, by particularly focusing on the breast
      cancer and various nanodelivery systems used for targeting action. 

PMID- 23865077
TI  - Human platelet antigen alleles in 998 Taiwanese blood donors determined by
      sequence-specific primer polymerase chain reaction.
AB  - Polymorphism of human platelet antigens (HPAs) leads to alloimmunizations and
      immune-mediated platelet disorders including fetal-neonatal alloimmune
      thrombocytopenia (FNAIT), posttransfusion purpura (PTP), and platelet transfusion
      refractoriness (PTR). HPA typing and knowledge of antigen frequency in a
      population are important in particular for the provision of HPA-matched blood
      components for patients with PTR. We have performed allele genotyping for HPA-1
      through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using
      sequence-specific primer polymerase chain reaction. The HPA allele frequency was
      99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81,
      and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and
      1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29%
      for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important,
      followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR
      based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on
      their immunogenicity. A larger-scale study will now be conducted to confirm these
      hypotheses and to establish an apheresis donor database for the procurement of
      HPA-matched apheresis platelets for patients with PTR.

PMID- 23865078
TI  - Dynamic folding pathway models of the Trp-cage protein.
AB  - Using action-derived molecular dynamics (ADMD), we study the dynamic folding
      pathway models of the Trp-cage protein by providing its sequential conformational
      changes from its initial disordered structure to the final native structure at
      atomic details. We find that the numbers of native contacts and native hydrogen
      bonds are highly correlated, implying that the native structure of Trp-cage is
      achieved through the concurrent formations of native contacts and native hydrogen
      bonds. In early stage, an unfolded state appears with partially formed native
      contacts (~40%) and native hydrogen bonds (~30%). Afterward, the folding is
      initiated by the contact of the side chain of Tyr3 with that of Trp6, together
      with the formation of the N-terminal alpha -helix. Then, the C-terminal
      polyproline structure docks onto the Trp6 and Tyr3 rings, resulting in the
      formations of the hydrophobic core of Trp-cage and its near-native state.
      Finally, the slow adjustment processes of the near-native states into the native
      structure are dominant in later stage. The ADMD results are in agreement with
      those of the experimental folding studies on Trp-cage and consistent with most of
      other computational studies. 

PMID- 23865079
TI  - Loss of RASSF1A expression in colorectal cancer and its association with K-ras
      status.
AB  - BACKGROUND: The RAS-association domain family 1 A (RASSF1A) is a classical member
      of RAS effectors regulating cell proliferation and apoptosis. Loss of RASSF1A
      expression may shift the balance towards a growth-promoting effect without the
      necessity of activating K-ras mutations. Its potential association with K-ras
      mutations in colorectal cancer (CRC) is unclear. METHODS: RASSF1A expression was
      examined in normal mucosa, adenoma, and tumor tissues of colon and rectum,
      respectively. We examined the association of RASSF1A expression, mutations of K
      ras, and EGFR status in 76 primary CRCs. The relationship between
      clinicopathological characteristics and RASSF1A expression was also analyzed.
      RESULTS: RASSF1A expression level decreased progressively in normal mucosa,
      adenoma and, tumor tissues, and the loss of RASSF1A expression occurred more
      frequently in tumor tissues. Of 76 primary CRCs, loss of RASSF1A expression
      and/or K-ras mutations were detected in 77% cases. Loss of RASSF1A expression was
      more frequent in K-ras wild-type than in mutation cases (63% versus 32%, P =
      0.011). CONCLUSIONS: Our study indicates that loss of RASSF1A may be involved in
      pathogenesis of CRC, its expression was found predominantly in K-ras wild-type
      CRCs, suggesting that it may be another way of affecting RAS signaling, in
      addition to K-ras mutations.

PMID- 23865081
TI  - Gastric emptying test: a useful functional study rarely applied.

PMID- 23865080
TI  - Single nucleotide polymorphism in the promoter of the human interleukin-13 gene
      is associated with asthma in Malaysian adults.
AB  - Asthma susceptibility genes are mapped to a region on human chromosome 5q31-q33,
      which contains a cluster of proinflammatory cytokine genes such as interleukin-13
      (IL-13), which is associated with asthma. This study investigated the allele
      frequencies of two single nucleotide polymorphisms (SNPs) (-1111C>T and 4257C>A)
      in the IL-13 gene between asthmatics and healthy volunteers as well as the
      relationship between these SNPs and IL-13 production. DNA extracted from buffy
      coat of asthmatic and control subjects was genotyped using the PCR-RFLP method.
      Amount of IL-13 produced by mitogen-stimulated peripheral blood leucocytes PBLs
      (PBLs) was determined by ELISA. The frequencies of the -1111C and 4257G wild-type
      alleles were 0.52 and 0.55 in asthmatics and were 0.67 and 0.56 in controls. A
      significant (P < 0.05) association was found between genotype and allele
      frequencies of SNP at position -1111C>T between asthmatic and control groups (OR,
      1.810; 95% CI = 1.184 to 2.767; P < 0.05). The mitogen-stimulated PBLs from
      asthmatics produced higher amounts of IL-13 production (P < 0.001). The 4257GA
      heterozygous and 4257AA homozygous mutant alleles were associated with higher IL
      13 production in asthmatics (P < 0.05). Our results show that the -1111T mutant
      allele are associated with asthma and the 4257A mutant alleles are associated
      with elevated IL-13 production.

PMID- 23865082
TI  - Is there a link between Hashimoto's thyroiditis and primary hyperparathyroidism?
      A study of serum parathormone and anti-TPO antibodies in 2267 patients.
AB  - According to various authors, thyroid disorders like Hashimoto's thyroiditis
      (HT), diffuse goiter or multinodular goiter, Graves' disease, medullary or
      papillary carcinoma could be found in a number of patients with primary
      hyperparathyroidism (PHPT). This association is more common in elderly women.
      Neck irradiation, lithium treatment and elevated TSH levels have been suggested
      as some of the possible causes of this co-existance. The aim of this study was to
      investigate and determine the prevalence of patients having both HT and PHPT, and
      the possible relation between these two diseases. We conducted a prospective
      study during three and a half years. This study included 45,231 patients, which
      were referred by their general practitioner or endocrinologist, under suspicion
      of having thyroid and/or parathyroid disease. In these patients we measured serum
      levels of the following parameters: anti-thyroid peroxidase antibodies (antiTPO
      Ab), anti-thyroglobulin antibodies (Tg-Ab), anti-TSH-receptor antibodies (TSHR
      Ab), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium
      (Ca). In 2,267 of these 45,231 patients (5.01%) we noticed elevated antiTPO-Ab
      (3542+/-3407IU/mL), with statistical significant difference from normal values
      (normal range 0-70IU/mL), P<0.05, and normal levels of other antithyroid
      antibodies (Tg-Ab, TSHR-Ab). All patients with elevated antiTPO-Ab were assumed
      to have HT. Within this group, 43 patients (1.89%) also had elevated serum levels
      of PTH (112.4+/-33.2pg/mL, normal range 8-76pg/mL) as well as elevated serum
      levels of calcium (2.92+/-0.06mmol/L, normal range 2.2-2.65mmol/L). These
      laboratory findings, accompanied with clinical symptoms, satisfied the criteria
      for PHPT. The mean age in this subgroup was 60.5+/-12.2 years. All 2,267 patients
      had normal or slightly elevated TSH levels. In conclusion, although the reported
      rate of prevalence of PHPT in the general population is about 0.3%, our results
      indicated a 1.89% occurrence of PHPT in 2267 patients with HT in central Serbia.
      This may be due to the autoimmune inflammatory process in HT supporting PHPT to
      PTH or calcium supporting HT or to common genetical predisposition of both
      entities.

PMID- 23865083
TI  - Assessment of salivary gland function in patients after successful kidney
      transplantation using (99m)Tc-pertechnetate salivary gland scintigraphy.
AB  - Chronic renal failure and its treatment can induce oral health problems and
      salivary glands dysfunction. The purpose of this study was to assess salivary
      glands function in patients with kidney transplantation using technetium-99m
      pertechnetate ((99m)Tc-P) salivary glands scintigraphy. We prospectively studied
      34 patients with kidney transplantation (30 males and 4 females,mean age 39.76+/
      11.6 years) and 28 healthy controls (12 males and 16 females, mean age 36.1+/-9.5
      years). Salivary gland scintigraphy was performed nearly 4.4+/-2.9 years after
      successful kidney transplantation. Dynamic salivary glands scintigraphy was
      performed during 25min after the intravenous administration of 185MBq of (99m)Tc
      P. Time-activity curves and glands functional parameters were calculated for the
      parotid and submandibular salivary glands: uptake ratio, maximum accumulation of
      the radionuclide, and excretion fraction. Statistical analysis of the functional
      parameters showed no significant differences between patients with kidney
      transplantation and healthy controls (P>0.05). In conclusion, this study showed
      that using (99m)Tc-P salivary gland scintigraphy, salivary glands function of
      patients with successful kidney transplantation do not differ statistically from
      those in healthy controls. 

PMID- 23865084
TI  - Positron emission tomography in chronic obstructive pulmonary disease.
AB  - The purpose of this paper was to systematically search the literature on (18)F
      fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the management
      of chronic obstructive pulmonary disease (COPD) and to provide a concise review
      of the reported results. Papers were searched through PubMed, EMBASE and Cochrane
      Library using the MESH terms "pulmonary disease, chronic obstructive", "pulmonary
      emphysema", and "positron-emission tomography". Of the 38 citations from the
      search and from browsing the literature lists of selected articles, seven
      relevant reports were identified. The sparse and heterogeneous literature
      available provide some indication that (18)F-FDG-PET could prove useful in COPD
      by a) differentiating COPD from chronic asthma and alpha-1-antitrypsin
      deficiency, b) measuring pulmonary and systemic inflammation to guide treatment
      and estimate prognosis, c) quantifying respiratory muscle use, and d) diagnosing
      cor pulmonale. In conclusion, the role of (18)F-FDG-PET in diagnosing and
      managing COPD patients seems to be promising and deserves to be further studied. 

PMID- 23865085
TI  - Is there a role for Nuclear Medicine in diagnosis and management of patients with
      primary aldosteronism?
AB  - Primary aldosteronism (PA) is the most common cause of secondary hypertension.
      The diagnosis of PA is of clinical importance for choosing the appropriate
      treatment, meaning, surgery for the unilateral disease, and inclusion of
      aldosterone antagonists in the antihypertensive treatment for the bilateral
      disease. Current diagnostic approaches showed that the prevalence of PA is much
      higher than previously estimated. There is still controversy regarding the true
      prevalence of PA in hypertensive patients. The gold standard for differentiating
      between unilateral and bilateral disease is the adrenal vein sampling (AVS), a
      method that is invasive and is performed accurately in only few dedicated
      centers. Non invasive methods (imaging) for discriminating the two entities are:
      the CT scan, MRI and iodocholesterol (NP-59) scintigraphy performed under
      dexamethasone suppression. But the accuracy of imaging compared to AVS is
      suboptimal and can result in wrong therapeutic decisions. NP-59 scintigraphy is a
      non-invasive functional imaging technique that reveals the adrenal cortical
      autonomic function and could have of incremental value over anatomical imaging.
      In conclusion, in previous years NP-59 scintigraphy was used infrequently, but
      recently with the advent of hybrid single photon emission tomography (SPET/CT)
      systems the interest in NP-59 scintigraphy has been renewed. Studies comparing NP
      59 SPET/CT imaging with AVS are warranted in order to establish its diagnostic
      accuracy. 

PMID- 23865086
TI  - Radioiodine SPET/CT guided needle aspiration as a useful technique for recurrence
      surveillance in a thyroidectomized differentiated thyroid cancer patient with
      negative US and serum Tg and positive Tg of the lymph node aspirate.

PMID- 23865087
TI  - Determination of trace amount of Cu2+ with a multi-responsive colorimetric and
      reversible chemosensor.
AB  - A multi-responsive sensor 1 was constructed by combining a ferrocene unit and a
      rhodamine block via a carbohydrazone bond. The sensor showed high selectivity
      toward Cu(2+) over other common metal ions in a wide pH range with excellent
      reversibility and rapid response. The obvious color change from colorless to pink
      upon the addition of Cu(2+) could make it a suitable 'naked-eye' indicator for
      Cu(2+). The detection limit (LOD) obtained was down to 2.0 nM and the association
      constant (Ka) was evaluated as 4.65 * 10(7) M(-1). The accuracy for detecting
      Cu(2+) in environmental river water was compared favorably with the traditional
      atomic absorption spectroscopy method (AAS). Finally, we proposed a reversible
      ring-opening mechanism (Off-On) of the rhodamine spirolactam induced by Cu(2+)
      binding and a 2 : 1 stoichiometric structure between 1 and Cu(2+). 

PMID- 23865088
TI  - A reversible fluorescent logic gate for sensing mercury and iodide ions based on
      a molecular beacon.
AB  - A simple, rapid, and reversible fluorescent DNA INHIBIT logic gate has been
      developed for sensing mercury (Hg(2+)) and iodide (I(-)) ions based on a
      molecular beacon (MB). In this logic gate, a mercury ion was introduced as the
      first input into the MB logic gate system to assist in the hybridization of the
      MB with an assistant DNA probe through the thymine-Hg(2+)-thymine interaction,
      which eventually restored the fluorescence of MB as the output. With this signal
      on process, mercury ions can be detected with a limit of detection as low as 7.9
      nM. Furthermore, when iodide ions were added to the Hg(2+)/MB system as the
      second input, the fluorescence intensity decreased because Hg(2+) in the thymine
      Hg(2+)-thymine complex was grabbed by I(-) due to a stronger binding force.
      Iodide ions can be detected with a limit of detection of 42 nM. Meanwhile, we
      studied the feasibility and basic performance of the DNA INHIBIT logic gate,
      optimized the logic gate conditions, and investigated its sensitivity and
      selectivity. The results showed that the MB based logic gate is highly selective
      and sensitive for the detection of Hg(2+) and I(-) over other interfering cations
      and anions. 

PMID- 23865089
TI  - Solid-state Forensic Finger sensor for integrated sampling and detection of
      gunshot residue and explosives: towards 'Lab-on-a-finger'.
AB  - Increasing security needs require field-deployable, on-the-spot detection tools
      for the rapid and reliable identification of gunshot residue (GSR) and
      nitroaromatic explosive compounds. This manuscript presents a simple, all-solid
      state, wearable fingertip sensor for the rapid on-site voltammetric screening of
      GSR and explosive surface residues. To fabricate the new Forensic Fingers, we
      screen-print a three-electrode setup onto a nitrile finger cot, and coat another
      finger cot with an ionogel electrolyte layer. The new integrated
      sampling/detection methodology relies on 'voltammetry of microparticles' (VMP)
      and involves an initial mechanical transfer of trace amounts of surface-confined
      analytes directly onto the fingertip-based electrode contingent. Voltammetric
      measurements of the sample residues are carried out upon bringing the working
      electrode (printed on the index finger cot) in direct contact with a second
      finger cot coated with an ionogel electrolyte (worn on the thumb), thus
      completing the solid-state electrochemical cell. Sampling and screening are
      performed in less than four minutes and generate distinct voltammetric
      fingerprints which are specific to both GSR and explosives. The use of the solid,
      flexible ionogel electrolyte eliminates any liquid handling which can resolve
      problems associated with leakage, portability and contamination. A detailed study
      reveals that the fingertip detection system can rapidly identify residues of GSR
      and nitroaromatic compounds with high specificity, without compromising its
      attractive behavior even after undergoing repeated mechanical stress. This new
      integrated sampling/detection fingertip strategy holds considerable promise as a
      rapid, effective and low-cost approach for on-site crime scene investigations in
      various forensic scenarios. 

PMID- 23865099
TI  - Cytoplasmic droplets of painted turtle spermatozoa.
AB  - Epididymal sperm from the painted turtle (Chrysemys picta) possess a cytoplasmic
      droplet which is located eccentrically on the sperm midpiece. The droplet
      contains a large quantity of lipid droplets in addition to hollow vesicles and
      degenerate mitochondrial fragments. Lipid droplets are closely associated with
      mitochondrial membranes and may function in the formation or degradation of
      mitochondria. Cytoplasmic droplets become detached from the sperm midpiece in a
      coordinated manner shortly before the commencement of fall mating and are not
      observed on sperm recovered from the oviduct of females.

PMID- 23865100
TI  - Evidence appraisal of Savage JW, Weatherford BM, Sugrue PA, et al. Efficacy of
      surgical preparation solutions in lumbar spine surgery. J Bone Joint Surg Am.
      2012;94(6):490-494.

PMID- 23865101
TI  - Healthier hospital food can affect health of patients and the planet.

PMID- 23865102
TI  - Time out remains key weapon in fight against wrong-site surgeries.

PMID- 23865103
TI  - In focus: manufacturer's written instructions for use: a critical component.

PMID- 23865104
TI  - Special report: treatments for castration-resistant metastatic prostate cancer.

PMID- 23865105
TI  - Balloon sinus ostial dilation for treatment of chronic rhinosinusitis.

PMID- 23865106
TI  - Special report: multiple molecular testing of cancers to identify targeted
      therapies.

PMID- 23865107
TI  - Breast-specific gamma imaging (BSGI), molecular breast imaging (MBI), or
      scintimammography with breast-specific gamma camera.

PMID- 23865108
TI  - Multianalyte testing for the evaluation of adnexal masses.

PMID- 23865109
TI  - Preface. Embodiment and epigeness; theoretical and methodological issues in
      understanding the role of biology within the relational developmental system.

PMID- 23865110
TI  - Introduction: embodiment and epigenesis: a view of the issues.
AB  - Relational developmental systems' theories emphasize that any facet of individual
      structure or function is embodied with other features of the individual and with
      the characteristics of his or her proximal and distal ecology, including culture
      and history. Embodiment means that biological, psychological, and behavioral
      attributes of the person, in fusion with the contexts of human development, have
      a temporal parameter. Embodiment provides a basis for epigenetics across
      generations and for epigenetic (qualitative discontinuous) change across
      ontogeny. We describe how the chapters in this two-volume set present theory and
      research pertinent to the roles of evolutionary and ontogenetic processes in
      cognitive, emotional, and behavioral development across the life span. The
      scholarship presented in these volumes suggests that rigorous, relational
      developmental theory-predicated research about the plastic, mutually influential
      relations among individual and ecological processes will enable developmental
      science to better describe, explain, and optimize the fundamental relational
      process of human development.

PMID- 23865111
TI  - Dynamic models of biological pattern formation have some surprising implications
      for understanding the epigenetics of development.
AB  - Nonlinear epigenetic processes are conceived of in terms of self-organizing
      dynamic models of biological pattern formation. Epigenetic processes thus
      conceived generate substantial subject-specific structural variation, for
      instance, in growing brain networks. It is shown that standard quantitative
      genetic modeling based on analyses of interindividual phenotypic variation
      misclassifies the variation generated by nonlinear epigenetic processes as being
      due to specific environmental influences. A new quantitative genetic model,
      iFACE, is introduced to correctly identify the structural variation generated by
      self-organizing epigenetic processes. iFACE is based on time series analysis of
      intraindividual variation of a single pair of genetically related subjects. The
      results of an application of iFACE to multilead EEG obtained with a single
      dizygotic twin pair is presented.

PMID- 23865112
TI  - A developmental systems approach to executive function.
AB  - According to recent claims from behavior genetics, executive function (EF) is
      almost entirely heritable. The implications of this claim are significant, given
      the importance of EF in academic, social, and psychological domains. This paper
      critically examines the behavior genetics approach to explaining individual
      differences in EF and proposes a relational developmental systems model that
      integrates both biological and social factors in the development of EF and the
      emergence of individual differences in EF. Problems inherent to behavioral
      genetics research are discussed, as is neuroscience research that emphasizes the
      plasticity of the prefrontal cortex. Empirical evidence from research on stress,
      social interaction, and intervention and training demonstrates that individual
      differences in EF are experience-dependent. Taken together, these findings
      challenge the claim that EF is almost entirely genetic but are consistent with an
      approach that considers biological differences in the context of social
      interaction.

PMID- 23865113
TI  - No genes for intelligence in the fluid genome.
AB  - Revolution is brewing belatedly within the heartlands of the genetic determinist
      establishment still in denial about the fluid genome that makes identifying genes
      even for common disease well-nigh impossible. The fruitless hunt for intelligence
      genes serves to expose the poverty of an obsolete paradigm that is obstructing
      knowledge and preventing fruitful policies from being widely implemented. Genome
      wide scans using state-of-the art technologies on extensive databases have failed
      to find a single gene for intelligence; instead, environment and maternal effects
      may account for most, if not all correlation among relatives, while identical
      twins diverge genetically and epigenetically throughout life. Abundant evidence
      points to the enormous potential for improving intellectual abilities (and
      health) through simple environmental and social interventions.

PMID- 23865114
TI  - The lost study: a 1998 adoption study of personality that found no genetic
      relationship between birthparents and their 240 adopted-away biological
      offspring.
AB  - In 1998, Robert Plomin and his Colorado Adoption Project (CAP) colleagues
      published the results of a longitudinal adoption study of personality. They found
      an average personality test score correlation of only 0.01 between birthparents
      and their 240 adopted-away 16-year-old biological offspring, suggesting no
      genetic influences on personality. However, the researchers interpreted their
      results in the context of previous twin studies, produced an average 14%
      heritability estimate, and concluded that nonadditive genetic factors underlie
      personality traits. The author challenges these conclusions and notes that the
      near-zero correlation stands in contrast to other types of behavioral genetic
      methods, such as twin studies, that are more vulnerable to environmental
      confounds and other biases. The author shows that authoritative psychology texts
      frequently fail to mention this 1998 CAP study. When it is mentioned, the
      original researchers' conclusions are usually accepted without critical analysis.
      The author also assesses the results in the context of the 20-year failure to
      discover the genes that behavioral geneticists believe underlie personality
      traits. He concludes that this 1998 investigation is a "lost study" in the sense
      that, although it is one of the most methodologically sound behavioral genetic
      studies ever performed, its results are largely unknown.

PMID- 23865115
TI  - A relational developmental systems approach to moral development.
AB  - Morality and cooperation are central to human life. Psychological explanations
      for moral development and cooperative behavior will have biological and
      evolutionary dimensions, but they can differ radically in their approach to
      biology. In particular, many recent proposals have pursued the view that aspects
      of morality are innate. We briefly review and critique two of these claims. In
      contrast to these nativist assumptions about the role of biology in morality, we
      present an alternative approach based on a relational developmental systems view
      of moral development. The role for biology in this approach is in setting up the
      conditions--the developmental system--in which forms of interaction and later
      forms of thinking emerge.

PMID- 23865116
TI  - Adolescent rationality.
AB  - Adolescents are commonly seen as irrational, a position supported to varying
      degrees by many developmentalists, who often appeal to recent research on
      adolescent brains. Careful review of relevant evidence, however, shows that (1)
      adults are less rational than is generally assumed, (2) adolescents (and adults)
      are categorically different from children with respect to the attainment of
      advanced levels of rationality and psychological functioning, and (3) adolescents
      and adults do not differ categorically from each other with respect to any
      rational competencies, irrational tendencies, brain structures, or neurological
      functioning. Development often continues in adolescence and beyond but
      categorical claims about adolescents as distinct from adults cannot be justified.
      A review of U.S. Supreme Court decisions concerning intellectual freedom,
      reproductive freedom, and criminal responsibility shows ongoing ambivalence and
      confusion about the rationality of adolescents. Developmental theory and research
      suggest that adolescents should be conceptualized as young adults, not immature
      brains, with important implications for their roles, rights, and
      responsibilities.

PMID- 23865117
TI  - Developing through relationships: an embodied coactive systems framework.
AB  - In recent decades, the developmental sciences have undergone a relational turn.
      Epigenetic (Gottlieb & Lickliter, 2007), embodied (Thompson, 2007), relational
      (Lerner & Overton, 2008) and systems (Kelso, 2003) approaches are transforming
      the ways in which we think about the nature and origins of psychological
      structures. At their most basic level, relational and systems approaches analyze
      the developmental origins of order and variability not in terms of sets of
      separable causal forces but instead in analyses of relations between causal
      systems. From this view, genes and environment, biology and culture, cognition
      and emotion, self and other, and so forth are inseparable as causal processes in
      the development of action and experience. Drawing on these principles, this paper
      contains an outline of an embodied coactive systems framework for understanding
      how individual psychological structures develop as a product of socially
      distributed coactions that occur among elements of the extended person
      environment system. Based on these principles, a system for the Developmental
      Analysis of Joint Action is described. This system provides a set of conceptual
      and empirical tools for making precise assessments of dynamic structure of
      jointly constructed patterns of thinking, feeling and acting. By tracking
      developmental changes in joint action, the system allows researchers to track the
      origins of higher order psychological structures through particular sequences of
      coconstructive activity. The holistic analytic system is illustrated through
      microdevelopmental analyses of (1) the joint construction of shoe-tying skill
      between a 5-year-old boy and a caregiver, and (2) socioemotional organization
      developing representations of self in a young adult over the course of a single
      session of psychotherapy.

PMID- 23865118
TI  - Multiple trajectories in the developmental psychobiology of human handedness.
AB  - We show that handedness is a product of a multifaceted biosocial developmental
      process that begins prenatally and continues into adulthood. Although right
      handedness predominates, handedness varies continuously across the population.
      Therefore, our phrase "multiple trajectories"refers to both differences in
      developmental pathways that can lead to similarities in handedness and
      similarities in pathways that can lead to differences in handedness. The task for
      the researcher is to identify how, when, and for what actions the trajectory of
      handedness development can be maintained or changed for an individual. Given the
      complexity of these developmental pathways, it is likely that the asymmetric
      sensorimotor activity that occurs during the development of handedness influences
      other hemispheric variations in neural processing. Indeed, researchers have
      investigated how handedness relates to cognitive, social, and emotional
      functioning because handedness represents different patterns of hemispheric
      specialization. Although the story of handedness development is not complete, it
      is well worth pursuing because it makes the development of brain-behavior
      relations more transparent, especially for hemispheric differences in function.

PMID- 23865119
TI  - Positive movement experiences: approaching the study of athletic participation,
      exercise, and leisure activity through relational developmental systems theory
      and the concept of embodiment.
AB  - Exercise and athletic participation are widely recognized as important aspects of
      healthy lifestyles and human development; yet most of the research on youth
      athletic participation, exercise, and leisure activity has not yet adopted a
      theoretical framework useful for understanding the development of individual
      engagement with these movement contexts. In order to gain an adequate
      understanding of the developmental experiences of involvement in movement
      contexts, understanding the role of the active individual and the mutually
      influential relations between individual and context are important. In this
      chapter, we present a new approach to the study of involvement in movement
      contexts, using relational developmental systems theory and the concept of
      embodiment to forward the idea of positive movement experiences (PMEs). The
      concept of PMEs may facilitate better understanding of involvement in movement
      contexts as a fundamental component of human life in general, and of youth
      development in particular.

PMID- 23865120
TI  - Integration of culture and biology in human development.
AB  - The challenge of integrating biology and culture is addressed in this chapter by
      emphasizing human development as involving mutually constitutive, embodied, and
      epigenetic processes. Heuristically rich constructs extrapolated from cultural
      psychology and developmental science, such as embodiment, action, and activity,
      are presented as promising approaches to the integration of cultural and biology
      in human development. These theoretical notions are applied to frame the nascent
      field of cultural neuroscience as representing this integration of culture and
      biology. Current empirical research in cultural neuroscience is then synthesized
      to illustrate emerging trends in this body of literature that examine the
      integration of biology and culture.

PMID- 23865121
TI  - Evolution in research and editing.

PMID- 23865122
TI  - Comparison of efficacy and safety of topiramate with gabapentin in migraine
      prophylaxis: randomized open label control trial.
AB  - OBJECTIVE: To compare the efficacy and safety of topiramate with gabapentin in
      the prophylaxis of migraine patients. METHODS: A 12-week randomised open label
      control trial was conducted at the Department of Pharmacology and Therapeutics,
      Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre (JPMC),
      Karachi from January to March 2011 involving 80 outpatients who had a history of
      migraine. The sample was divided into two equal groups. Primary efficacy measure
      was changed into mean monthly migraine frequency. Secondary efficacy measure
      included reduction in severity and average duration of an attack. Chi square test
      and paired t-test were used to analyse the data through SPSS 15. RESULT:
      Reduction in mean monthly migraine frequency (10.67 +/- 4.25 to 1.82 +/- 2.02) in
      the topiramate group was significantly greater compared with (11.97 +/- 4.452 to
      2.73 +/- 2.59) that in the gabapentin group (p < 0.001). Reduction in severity
      from 6.60 +/- 2.122 to 1.03 +/- 0.92 in the topiramate group was also
      significantly greater compared with 6.93 +/- 1.90 to 1.18 +/- 1.01 in the
      gabapentin group (p < 0.001). Reduction in the average duration of attacks from
      25.77 +/- 22.32 hours to 1.05 +/- 1.06 hours in the topiramate group was
      significantly greater compared with 22.20 +/- 20.72 to 1.08 +/- 1.40 hours in the
      gabapentin group (p < 0.001). Weight loss and numbness were common adverse
      effects in the topiramate group. Dizziness, weight gain and somnolence were
      reported in the gabapentin group. CONCLUSION: Gabapentin appeared well tolerated
      in 30 (75%) patients compared to topiramate in 23(57.5%) patients. Both drugs
      were equally effective in migraine prophylaxis.

PMID- 23865123
TI  - The effect of ginger for relieving of primary dysmenorrhoea.
AB  - OBJECTIVE: To assess the effectiveness of ginger in providing relief to patients
      of primary dysmenorrhoea. METHODS: The clinical trial was conducted at Toyserkan
      Azad University in western Iran from July 10 to September 5, 2010. It comprised
      of 70 female students of the university with primary dysmenorrhoea.The subjects
      were randomly divided in to two equal groups and were given either placebo or
      ginger in capsule form for 3 days in first menstruation cycles. They graded the
      severity of their pain using a visual analogue scale. A 5-point Likert scale was
      used to assess response to treatment. Wilcoxor's rank-sum test was used to
      compare the severity of pain in the two groups. RESULTS: Compared with the
      baseline, the decrease in the visual analogue scores of post-therapy pain in the
      ginger group was significantly greater than that for placebo group. In the ginger
      group, 29 (82.85%) subjects reported an improvement in nausea symptoms, compared
      with 16 (47.05%) in the placebo group. CONCLUSION: Ginger is effective in
      minimising the pain severity in primary dysmenorrhoea.

PMID- 23865124
TI  - Induction position for spinal anaesthesia: sitting versus lateral position.
AB  - OBJECTIVE: To compare the effect of induction position on block characteristics
      (sensory and motor nerves) and haemodynamic stability in elderly patients with
      isobaric bupivacaine. Patient comfort was also looked at. METHODS: The randomized
      single blinded study was conducted at the Aga Khan University Hospital, Karachi,
      from September 2007 to August 2008. A total of 70 patients aged >60 years of both
      genders were included. Spinal anaesthesia was performed either in sitting or
      lateral position according to random allocation. Assessments of sensory, motor
      block and heart rate, systolic and diastolic blood pressure were recorded for 20
      minutes. SPSS 16 was used for statistical analysis. RESULTS: There was no
      significant difference for haemodynamic variables heart rate, systolic and
      diastolic blood pressure. The onset of anaesthesia was faster in the sitting
      group (4.5 minutes vs 5.4 minutes). The motor block characteristics were similar
      in both the groups. The majority of patients who reported 'very comfortable' for
      induction position belonged to the lateral group. CONCLUSION: Both sitting and
      lateral positions have similar effects on sensory and motor blockade and
      haemodynamic stability. However, patients generally found lateral position very
      comfortable.

PMID- 23865125
TI  - Pattern of left ventricular hypertrophy seen on transthoracic echo in patients
      with hypertensive cardiomyopathy when compared with idiopathic hypertrophic
      cardiomyopathy.
AB  - OBJECTIVE: To explore the pattern of left ventricular hypertrophy caused by
      hypertension and to compare it with idiopathic hypertrophiccardiomyopathy.
      METHODS: The retrospective study was conducted at the echocardiography lab of
      Rashid Hospital, Dubai, from January 2009 to January 2010. Cases of 11 patients
      with significant left ventricular hypertrophy (septum > 15 mm) due to underlying
      hypertension were analysed and compared with 11 cases of idiopathic hypertrophic
      cardiography (septum >15mm) to assess the two groups with similar baseline
      echocardiographic features. Minitab software was used for statistical analysis.
      RESULTS: Although the pattern of hypertrophy in hypertensive patients was more
      concentric (n = 5; 45%), there was also asymmetrical septal hypertrophy in 4
      (36%) cases, particularly the elderly with sigmoid shape septum. There was
      evidence of resting mid-cavity gradient due to reduced left ventricular end
      systolic diametre in 4 (36%) cases. CONCLUSION: Although the equation between
      hypertension and left ventricular hypertrophy is more concentric, but it can be
      associated with left ventricular outflow tract obstruction and significant mid
      cavity gradients similar to that seen in idiopathic hypertrophic cardiomyopathy.

PMID- 23865126
TI  - Civilian perspective of firearm injuries in Bahawalpur.
AB  - OBJECTIVE: To study the firearm injury patterns, weaponry detail, etiological
      factors and offered management in civilian population. METHODS: The retrospective
      descriptive cross-sectional study was conducted at the Bahawal Victoria Hospital
      comprising 297 cases of civilian firearms fulfilling the inclusion criteria from
      January 2008 to December 2010. Medicolegal record of the hospital's Statistical
      Department was collected and recorded on a pre-designed proforma. RESULTS: Of the
      297 cases 248 (84%) related to men, and 49 (16%) to women. The age of patients
      ranged between 10 and 50 years, with a 5: 1 male-female ratio. There was an
      yearly increase in the number of patients, with 84 patients in 2008; 99 in 2009;
      and 114 in 2010. Weaponry detail was not available in 89 cases; hand-guns were
      used in 104 cases; hunting guns in 62 cases; and assault rifles in 42 cases.
      There were 178 (60%) injuries in civilian clashes; 59 (20%) in homicidal cases;
      and 30 (10%) in robbery encounters. Limbs were involved in 148 (50%) patients;
      abdomen injuries in 92 (31%) patients; thorax in 35 (12%) patients; head and neck
      in 18 (6%) patients; and multiple injuries in 6 (2%). Overall mortality was 36
      (12%). CONCLUSION: Hand-guns were the commonest weapons in civilian firearm
      injuries. Civilian clashes were the leading cause followed by homicidal and
      robbery events. Firearm injuries to the extremities were associated with severe
      morbidity. Laparotomy was used in the majority of abdominal firearms, while chest
      intubation was the mainstay in thoracic injuries.

PMID- 23865127
TI  - Clinicopathological analysis of malignant eyelid tumours in north-west Pakistan.
AB  - OBJECTIVE: To analyse the demography, mode of presentation, gross morphology,
      histopathological diagnosis and subsequent course of malignant eyelid tumours in
      north-west Pakistan. METHODS: The retrospective observational study was performed
      at the Department of Ophthalmology, Khyber Teaching Hospital, Peshawar, from
      January 2007 to July 2010, and comprised data related to 222 patients. Charts of
      patients with malignant eyelid tumours admitted to the department during study
      period were reviewed. Patients' demographic data, gross and microscopic features
      of the tumours and their subsequent course of treatments were recorded. SPSS 14
      was used for statistical analysis. RESULTS: Of the total, 122 (54.1%) patients
      were male and 102 (45.9%) were female. Mean age of all patients was 59.3 +/- 14.2
      years. Among the patients, 73 (32.9%) had the involvement of the lower lid; 57
      (25.7%) the upper lid; 18 (8.11%) the medial canthus; 2 (0.9%) the lateral
      canthus; and 72 (32.4%) had more than one region involved. On histopathology,
      basal cell carcinoma was the most common (n= 131; 59%), followed by squamous cell
      carcinoma in 70 (31.5%), sebaceous gland carcinoma in 15 (6.8%), malignant
      melanoma in 3 (1.3%) and undifferentiated carcinoma in 3 (1.3%) cases. Of the
      total tumours, 164 (73.87%) did not spread, and 58 (26.13%) spread either locally
      or distantly. CONCLUSION: Basal cell carcinoma was is the most common malignant
      eyelid tumour in the study. Squamous cell carcinoma, which was second, was found
      to be more common in north-west Pakistan than in any other part of Asia, while
      the sebaceous gland carcinoma was relatively less common.

PMID- 23865128
TI  - Accuracy of Doppler ultrasound in diagnosis of endometrial carcinoma.
AB  - OBJECTIVE: To determine the accuracy of Doppler ultrasound in the diagnosis of
      endometrial carcinoma in patients presenting with post-menopausal bleeding while
      taking histopathological findings as the gold standard. METHODS: The cross
      sectional study was done at the Department of Radiology, Bahawal Victoria
      Hospital, Bahawalpur, from April 1 to September 30, 2009, and comprised 128
      patients above 50 years of age having history of post-menopausal bleeding and who
      were referred to the department. Name, age and hospital registration number were
      recorded on a proforma. Doppler ultrasound was performed and endometrial
      thickness and uterine artery resistive index were recorded on transabdominal
      ultrasonography. Patients with endometrial thickness of more than 5 mm and
      uterine artery resistive index of less than 0.7 were considered to be having
      endometrial carcinoma. Histopathology findings were also recorded using the
      hospital registration number of the patient. The findings of Doppler ultrasound
      scan were validated with the findings of histopathology. RESULTS: Of the 128
      patients, 48 (37.5%) were between the ages of 51 and 55 years; 46 (35.93%) were
      in the 56-60 age group; and 34 (26.57%) were over 65 years. On the basis of
      Doppler ultrasound findings, 106 (82.8%) patients were diagnosed as having
      endometrial carcinoma, while 22 (17.19%) were declared negative. Ultrasonography
      results were compared with histopathology findings. The percentages of true
      positive, true negative, false positive and false negative were calculated. There
      were 103 (80.47%) true positive; 12 (9.37%) false positive; 10 (7.81%) true
      negative; and 3 (2.35%) false negative. Specificity, sensitivity, positive
      predictive value and negative predictive value were found to be 97.16%, 76%,
      89.56% and 76.92% respectively. CONCLUSION: The use of Doppler ultrasonography in
      non-invasive diagnosis of endometrial carcinoma in patients presenting with post
      menopausal bleeding was quite useful with good sensitivity, specificity, as well
      as positive and negative predictive values. There were no procedural
      complications.

PMID- 23865129
TI  - Efficacy of aprotinin treatment on bilateral blunt chest trauma created in
      rabbits.
AB  - OBJECTIVES: To investigate the effects of aprotinin, on blood gasses, oxidant
      antioxidant status, and lung histopathology in an experimental bilateral blunt
      chest trauma model. METHODS: Conducted at the Experimental Animal Laboratory of
      Meram Medical School at Selcuk University, Konya, Turkey, the study comprised 21
      New Zealand female albino rabbits who were divided into three groups.Trauma was
      applied on the sham and aprotinin groups, which was administered intravenous
      Aprotinin 20.000 U/kg. Arterial blood samples were obtained from all rabbits at
      hours 0, 3, 24, and 96. At hour 96 after trauma, all rabbits were sacrificed
      using the decapitation method, and then blood and lung tissue samples were
      obtained. Blood nitric oxide, malondialdehyde and blood gas measurements were
      made. Histopathological changes in the lung were examined with a light
      microscope. RESULTS: While no positive effect of aprotinin was observed on nitric
      oxide malondialdehyde and partial pressure of carbon dioxide values, it was seen
      to have an increasing effect on partial oxygen pressure level. Aprotinin had a
      partial effect on lung histopathology. CONCLUSION: Aprotinin was determined to
      have a positive effect on PO2 levels. We could not find any positive effects
      especially on alveolar haemorrhage.

PMID- 23865130
TI  - Decompressive craniectomy for acute subdural haematoma: an overview of current
      prognostic factors and a discussion about some novel prognostic parametres.
AB  - OBJECTIVE: To identify specific factors that can be used to predict functional
      outcome and to assess the value of decompressive craniectomy in patients with
      acute subdural haematoma. METHODS: The retrospective study was done at the
      Zonguldak Karaelwas University Practice and Research Hospital, Turkey, and
      included 34 trauma patients who had undergone decompressive craniectomy for acute
      subdural haematoma from 2001 to 2009. At the 30th day of the operation, the
      patients were grouped as survivors and non-survivors. Besides, based on their
      Glasgow Outcome Scale, which was calculated 6 months postoperatively, the
      patients were divided into two functional groups: favourable outcomes (4-5 on the
      scale), and unfavourable outcomes (1-3 on the scale). The characteristics of the
      groups were compared using SPSS 15 for statistical analysis. RESULTS: One-month
      mortality was 38.2% (n = 13) and 6-month total mortality reached 47% (n = 16).
      Patients with higher pre-operative revised trauma score, Glasgow coma scale,
      partial anterial pressure of carbon dioxide, arterial oxygen pressure, Charlson
      co-morbidity index score, blood glucose level, blood urea nitrogen, and lower age
      had a higher rate of survival and consequently a favourable outcome. Higher
      platelet values were only found to be a determinant of higher survival at the end
      of the first month without having any significant effect on the favourable
      outcome. CONCLUSION: In patients of traumatic acute subdural haematoma whose
      Glasgow coma scale on arrival was < or = 8, a massive craniectomy along with the
      evacuation of the haematoma, may be considered as a treatment option for intra
      operative and post-operative brain swelling. But in patients with a score of 3 on
      arrival and bilaterally fixed and dilated pupils, decompressive craniectomy is
      unnecessary.

PMID- 23865131
TI  - Women's attitude to group prenatal care and their satisfaction.
AB  - OBJECTIVE: To evaluate the attitude and satisfaction level of women attending
      prenatal clinics for getting group care in Iran. METHODS: The descriptive
      analytical study performed from 2009 to 2010, comprised of 701 pregnant women
      with gestational age of 20 weeks or more who had undergone at least two visits at
      15 prenatal care centres in Zanjan, Iran. Detailed questionnaire regarding
      overall satisfaction, communication skills, quality of the care, existing
      attitudes about group prenatal care, availability and costs of services etc was
      filled up through face-to-face interviews with each subject. Data was analysed
      using SPSS 11 and analysis of variance. RESULTS: Of the total, 489 (71%) subjects
      claimed that they preferred group prenatal care. The satisfaction level was found
      to be statistically significant according to the type of insurance (p < 0.001).
      The least and the most disappointed were subjects with private and social
      security insurances respectively. There was no significant relationship between
      satisfaction and age or level of maternal education, but the subjects said that
      the relationship with others in the group would have a severe effect on their
      learning. The overall satisfaction rate was more than 99% (n = 694). CONCLUSION:
      The high satisfaction level suggests good quality of care is being provided by
      the centres concerned. Moreover, most of the mothers had a positive attitude
      towards the concept and practice of group prenatal care.

PMID- 23865132
TI  - A prospective observational study of paediatric cardiac surgery outcomes in a
      postoperative intensive care unit in Iran.
AB  - OBJECTIVE: To evaluate the incidence of complications, morbidity and mortality,
      and the associated risk factors with mortality at a Paediatric Cardiology
      Intensiv Care Unit of a developing country. METHODS: The prospective
      observational study was conducted at Shahid Modarres Hospital, Tehran, Iran, from
      August 2009 to July 2010. A total of 202 patients were monitored from the time
      they entered the Paediatric Cardiology Intensive Care Unit till their final
      discharge. SPSS 16 was used for statistical analysis and p < or = 0.05 was
      considered statistically significant. RESULTS: Of the total, 107 (53%) were male
      and 95 (47%) were female. The mean age of the patients was 4.5 +/- 4.9 years
      (range: 2 days to 18 years). Among the patients 59 (29.2%) had complications and
      25 (12.37%) of them died. A total of 177 (87.6%) survived and were discharged.
      Infants (p = 0.012), cyanotic congenital heart disease (p = 0.002), longer
      duration of cardiopulmonary bypass (p = 0.027), longer aortic cross-clamp time (p
      = 0.038), longer mechanical ventilation time (p < 0.006), and early post
      operative period (p = 0.05) were associated factors for mortality. According to
      regression analysis, cyanotic congenital heart disease, longer intubation time,
      and early post-operative period were major factors for mortality (p = 0.01, p <
      0.001, and p = 0.001) respectively. CONCLUSION: Critically ill cyanotic young
      infants in the first 24 hours after operation experienced high mortality.
      Prolonged mechanical ventilation was also associated with high mortality.

PMID- 23865133
TI  - Rational use of antibiotics--a quality improvement initiative in hospital
      setting.
AB  - OBJECTIVES: To minimise irrational use of antibiotics by implementing guidelines
      for antibiotic usage in obstetrics and Gynaeocology. METHODS: The observational
      study was conducted from January to December 2010 at the maternity unit of Aga
      Khan Hospital for Women and children, Kharadar, a secondary care facility in
      Karachi, Pakistan. Data was collected from medical records related to the study
      period. Prophylactic antibiotics were given according to the American College of
      Obstetricians and Gynaecologists recommendation 2009. Surveillance was done by
      surgical site infection rates and infectious morbidity. Data was analysed on SPSS
      13. RESULTS: Therapeutic antibiotic use was rationalized, reducing the use of
      therapeutic antibiotics from 97% (n = 160/165) in January 2010 to 8% (n = 10/125)
      in December 2010. Surgical site infection rates were less than 5%. Cost of
      antibiotics per patient decreased by 90%. Decrease in the length of stay and
      workload on nursing staff was also observed. CONCLUSION: Implementing guidelines
      for antibiotic use in obstetrics and gynaecology and translating it into our
      protocols was effective in decreasing the irrational antibiotic consumption and
      increasing the rational use of antibiotics in the hospital.

PMID- 23865134
TI  - Role of decreased plasma tryptophan in memory deficits observed in type-I
      diabetes.
AB  - OBJECTIVE: To investigate the relationship between plasma tryptophan and the
      occurrence of memory dysfunctions in male and female type 1 diabetics. METHODS:
      The case-control study was conducted at two urban healthcare facilities in
      Karachi from January to June 2009, and comprised 100 diabetic subjects of among
      whom were 50 men and 50 women. The controls were also similar in number and
      gender. A questionnaire was used to evaluate the memory impairment in the
      subjects. Plasma tryptophan was determined by high performance liquid
      chromatography with ultra-violet method. Students' t test was used to analyse
      tryptophan data. RESULTS: There was considerable memory impairment in the cases
      (n = 40) compared to the controls (n = 5). Results also showed a significant (p <
      0.01) decrease in plasma tryptophan levels in both male and female diabetic
      patients. CONCLUSIONS: Diabetic subjects exhibited occurrence of memory
      impairment with concomitant decline in plasma tryptophan levels. The findings
      indicate that decreased brain uptake of tryptophan and lowered brain 5
      hydroxytryptamine levels may be responsible for the memory deficits seen in
      diabetics.

PMID- 23865135
TI  - Depression and health related quality of life in breast cancer patients.
AB  - OBJECTIVE: To investigate the prevalence of depression in women with breast
      cancer and relate it to their health-related quality of life. METHODS: The cross
      sectional study was conducted at the Imam Khomeini Hospital in Iran between
      January and December 2009, and comprised 60 women with breast cancer with a mean
      age of 43.8 +/- 47.12 years. In order to assess the health-related quality of
      life, the study used the parameters of the Iranian version of the Functional
      Assessment of Cancer Therapy for Breast Cancer. To identify expressive symptoms,
      the Beck Depression Inventory was used. General linear model regression and SPSS
      14 were used to analyse the data. RESULTS: Significant differences in the
      prevalence of depression between treatment types was found. The presence of
      depression was significantly correlated with poorer overall health-related
      quality of life and the four subscales of the protocol. The patients reported
      statistically significant effects of depression in the overall category (p=
      0.001). Participants with depression were more likely to have a poorer overall
      health-related quality of life, the exception being the social/family well-being
      subscale. CONCLUSIONS: Depression affects health-related quality of life in
      breast cancer patients. Although further studies are necessary to confirm our
      findings, but our results emphasise the necessity for better mental health
      strategies for such patients.

PMID- 23865136
TI  - Valproic acid induced hyperammonaemic encephalopathy.
AB  - OBJECTIVE: To observe clinical and laboratory features of valproic acid-induced
      hyperammonaemic encephalopathy in patients taking valproic acid. METHODS:
      Observational study was conducted at the Neurology Department, Dow University of
      Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20,
      2011. Ten patients on valproic acid therapy of any age group with idiopathic or
      secondary epilepsy, who presented with encephalopathic symptoms, were registered
      and followed up during the study. Serum ammonia level, serum valproic acid level,
      liver function test, cerebrospinal fluid examination, electroencephalogram and
      brain imaging of all the patients were done. Other causes of encephalopathy were
      excluded after clinical and appropriate laboratory investigations. Microsoft
      Excell 2007 was used for statistical analysis. RESULTS: Hyperammonaemia was found
      in all patients with encephalopathic symptoms. Rise in serum ammonia was
      independent of dose and serum level of valproic acid. Liver function was also
      found to be normal in 80% (n = 8) of the patients. Valproic acid was withdrawn in
      all patients. Three (30%) patients improved only after the withdrawal of valproic
      acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after
      sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%)
      patients and to more than half of the baseline level in two (20%) patients. Three
      (30%) patients were lost to followup after complete clinical improvement.
      CONCLUSION: Within therapeutic dose and serum levels, valproic acid can cause
      symptomatic hyperammonaemia resulting in encephalopathy. All patients taking
      valproic acid presenting with encephalopathic symptoms must be monitored for the
      condition.

PMID- 23865137
TI  - Surgical safety practices in Pakistan.
AB  - OBJECTIVES: To evaluate the current practices regarding formal or informal
      implementation of individual elements of the World Health Organisation's Surgical
      Safety Checklist in tertiary care hospitals of Karachi and to establish a pre
      checklist baseline to suggest a plan for implementation of the checklist.
      METHODS: The qualitative knowledge-attitude-practice (KAP) survey was conducted
      from May 1, 2009 to January 31, 2010, during whch 103 surgeries were observed in
      10 hospitals across Karachi based on simple stratified sampling. Initially, 15
      tertiary care hospitals were selected, but response and consent was received from
      10 of them. The WHO checklist was applied after some basic changes according to
      local needs and perspectives. The surgical teams were also observed for
      coordination and working harmony. The data was analysed on SPSS version 12 and
      statistical tests were applied accordingly. RESULTS: Of the 103 surgeries
      observed, 13 (13.4%) patients did not confirm their identity, site of surgery or
      procedure. There was no concept of timeout in 91 (88.5%) cases, while in 52
      (53.8%) cases, the anaesthetist did not ask for known allergy, and prophylaxis
      antibiotic was not given in 36 (37.5%) cases. In 20 (21.2%) cases, sponge, needle
      and instruments were not counted. CONCLUSION: The results suggest that the safety
      of surgical patients in the operating theaters in hospitals under review was far
      from satisfactory. Introduction of and adherence to a safety checklist would
      result in significant reduction in death and complication rate.

PMID- 23865138
TI  - The relationship between menarche age and anthropometric indices of girls in
      Sabzevar, Iran.
AB  - OBJECTIVE: To determine the relationship between anthropometric indices and the
      age of menarche in female students of Sabzevar, Iran. METHODS: The cross
      sectional study was conducted in Sabzevar, Iran, from April to September 2010,
      and involved girls of 11-18 years of age. The required sample size for analysing
      the relationship between menarche age and Body Mass Index was estimated to be 110
      by correlation coefficient and Cox survival regression model and by using the
      NCSS_PASS software. The study had 130 students who were selected by multi-stage
      probability sampling. Relevant data were collected through a questionnaire as
      well as by measuring the anthropometric indices such as height, weight etc.
      Analysis of data was done by independent t-test, Pearson's correlation
      coefficient, Chi-square, Kaplan-Meier and Cox survival regression model using
      SPSS 15. RESULTS: The mean menarche age was 12.5 +/- 1.4 years. Mean body mass
      index, weight and height of the menstruated girls were higher and significant
      than the corresponding figures of the non-menstruated girls. The correlation
      coefficient showed a significantly negative relation between body mass index and
      menarche age (r = -0.221, p = 0.025 (but correlation between menarche age and
      height or weight was not significant. Menarche occurrence rate was significantly
      higher in overweight girls than girls with normal weight. Menarche occurrence
      rate in girls with low weight was lower than those of normal weight. CONCLUSION:
      The menarche age and body mass index are significantly related; the higher body
      mass index, the lower was the menarche age, resulting in a higher menarche
      occurrence rate.

PMID- 23865139
TI  - A comparison of public and private hospital on rational use of blood in
      Islamabad.
AB  - OBJECTIVE: To assess rational use of blood and blood products in adults treated
      in surgical and allied departments in a public and a private hospital in
      Islamabad. METHODS: The comparative cross-sectional study was conducted from
      April 15 to June 15, 2011, in Islamabad. A total of 350 patients were enrolled
      using universal sampling; 170 (48%) from the public and 180 (52%) from the
      private hospital. Data was collected using a pre-tested questionnaire on age,
      gender, department, haemoglobin levels, indications of blood transfusions, types
      of product advised, total number of units ordered, cross-matched and transfused.
      Rational use of blood was assessed by determining prevalence of appropriateness
      using World Health Organisation's clinical practical guidelines and transfusion
      indices.Ten in-depth interviews were done with doctors to assess their knowledge
      and practices. SPSS 15 was used for statistical analysis. RESULT: In the public
      hospital, appropriate use of blood was only 54.1% (n = 92) as compared to the
      private hospital where the appropriateness was 69.4% (n = 125). The cross-matched
      to-transfusion ratio was 1.1 and 2.7, where transfusion index was 2.6 and 2.5 in
      public and private hospital respectively. Doctors had good clinical knowledge,
      but were not using any guidelines. CONCLUSION: Neither the public nor the private
      hospital was rational in use of blood.

PMID- 23865140
TI  - Determinants of HIV sero-conversion among male injection drug users enrolled in a
      needle exchange programme at Karachi, Pakistan.
AB  - OBJECTIVE: To assess the determinants of HIV sero-conversion among male injection
      drug users enrolled in needle exchange programme at Karachi. METHODS: An
      unmatched retrospective case control study was conducted among male injection
      drug users receiving needle exchange services in Karachi. The cases and controls
      were identified from one drop in center providing needle exchange services. The
      data for the study participants was collected retrospectively from the programme.
      Descriptive statistics, univariat analysis, and multivariate regression analysis
      for determinants of HIV sero-conversion and Hosmer and Lameshow goodness of fit
      test for model adequacy were performed. RESULTS: Mean age of the study
      participants was 34.17 +/- 10.74 years. Average monthly income of the
      participants was US$ 125.15 +/- 76.32. In unconditional multivariate regression
      analysis being unmarried (AOR: 3.0 95% CI 1.14-7.9, p=0.02), not living with
      family (AOR: 2.8 95% CI 1.18-6.79 p = 0.02), family history of addiction (AOR:
      2.5, 95% CI 1.01-6.49, p = 0.04), injecting drugs in groups (AOR: 2.8, 95% CI
      1.12 7.02 p=0.02), not obtaining syringes from the programme (AOR: 26.45, 95% CI
      2.47-282.8 p = 0.007), and history of blood transfusion (AOR: 52.9, 95% CI 1.32
      2118.416 p = 0.03) were significantly associated with HIV positive sero-status.
      Model adequacy was assessed by Hosmer and Lameshow goodness of (J: 4.95, p = 0.7)
      indicating that the model was accurate. CONCLUSION: Social and drug related risky
      behaviours are important determinants of HIV among male IDUs in Karachi. The
      situation calls for programmematic initiatives for addressing the risky
      behaviours among IDUs for effective control of epidemic in the country.

PMID- 23865141
TI  - Are we ready for a new epidemic of under recognized liver disease in South Asia
      especially in Pakistan? Non alcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as an
      important public health problem nowadays. NAFLD encompass a variety of liver
      pathologies including simple steatosis, NASH, fibrosis, cirrhosis and finally
      cancer. It is associated with obesity, metabolic syndrome, dyslipidaemia, Insulin
      resistance (IR) and type 2 diabetes. It is the most common chronic liver disease
      in USA and considered to be increasing in Asia Pacific region including South
      Asia however there is no community based study from Pakistan. Customarily NAFLD
      had been regarded as a benign disease; however clinical as well as
      epidemiological studies had contradicted this belief because approximately 20% of
      the patients with NAFLD had NASH which has propensity to develop cirrhosis and
      ultimately to HCC. The diagnosis of NAFLD is made most of the times incidentally
      on abdominal imaging which is done for other purposes. Despite its prevalence,
      treatment options are very limited. However modification of risk factors such as
      dyslipidemia, diabetes control and weight reduction does help in NAFLD. Fatty
      liver results due to lack of physical activity; hence foremost step to manage
      such patients would be to develop the healthy life style. We need population
      based studies in our country so that we can protect our population from a new
      epidemic.

PMID- 23865142
TI  - Ray of hope: opportunities for reducing unsafe abortions!
AB  - Unsafe abortion is one of the leading causes of maternal mortality and morbidity
      which impede the nation in achieving the targets of MDG 5. In the developing
      world, it is estimated that 13% of all maternal deaths are due to unsafe
      abortions. Despite having certain liberty in the law and religion, Pakistan has a
      relatively high prevalence of unsafe abortion. Poverty, unintended pregnancies,
      ineffective use of contraceptive methods and unawareness about the law are the
      root causes for the rise in the number of women seeking abortions. Nonetheless,
      with all these opening points of having permission in the law and religion could
      direct us that if we just follow them we can reduce the number of unsafe and
      illegal abortions.Therefore, there is a strong interventions would be required in
      health and legal aspects, which would decrease maternal mortality and morbidity.

PMID- 23865143
TI  - Assessment of experimental animal model for training obstetric anal sphincter
      injury techniques.
AB  - The Multiparous Goat Pelvic Model was used to train obstetricians and residents
      for perineal and anal sphincter anatomy and techniques of repair of Obstetric
      Anal Sphincter Injuries (OASIs). The purpose of this study was to assess the
      similarity of this model with human anatomy and the usefulness of goat model for
      training obstetricians for perineal tears. Six workshops were conducted between
      June 2009 and December 2010. A total of 90 participants, including 64(70.3%)
      residents and 26(28.5%) consultants in Obstetrics and Gynaecology, attended hands
      on training workshops using experimental goat pelvic model for the repair of
      perineal tears. Among the consultants, 23 (88.5%), and 60 (93.7%) residents could
      easily identify the goat anal sphincter. With reference to the similarity to
      human vaginal dimensions, 20 (76.9%) consultants and 43(67.1%) residents found it
      to be similar with human anatomy. Evaluating the anal canal anatomy, 22 (84.6%)
      consultants and 34(53.1%) residents reported it to be similar to the human anal
      canal. The perineal body anatomy was reported as very different by both
      consultants and residents (80% and 67.9% respectively). All the consultants and
      49(76.5%) of the residents strongly recommended the use of this model for future
      hands-on workshops.

PMID- 23865144
TI  - Genetics of non-syndromic autosomal recessive mental retardation.
AB  - Non-syndromic mental retardation is one of the most serious neurodevelopmental
      disorders, which has a serious impact not only on the affected individuals and
      their families but also on the health care system and society. Previously
      research has been more focused on the X-linked mental retardation and only
      recently studies have shown that non-syndromic autosomal recessive mental
      retardation is extremely heterogeneous and contributes much more than the X
      linked mental retardation. But very little is known about the genes and loci
      involved in nonsyndromic autosomal recessive mental retardation than the X-linked
      mental retardation. To date only thirty loci and ten genes have been established
      associated with the non-syndromic autosomal recessive mental retardation. This
      short review presents an overview of the current knowledge on clinical
      information available for the ten genes associated with this unexplored group of
      genetic disorder.

PMID- 23865145
TI  - Cutaneous metastasis of bilateral renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of
      metastasis. However, metastasis from RCC to the skin is much less common. It is
      virtually a sign of poor prognosis. We represent a 42 years old man with
      bilateral RCC of clear cell type followed by metastasis to the scalp one month
      later. In this case the relatively young age of the patient, bilaterality of RCC
      and occurance of skin metastasis in the absence of recurrent kidney tumour are
      interesting.

PMID- 23865147
TI  - Common presentation uncommon diagnosis primary omental torsion.
AB  - Primary omental torsion is a rare cause of acute abdomen and mimics common acute
      abdominal condition like appendicitis. Torsion of the greater omentum may be
      primary or secondary. Here we present 2 cases admitted through emergency with the
      pain in right iliac fossa with this unusual diagnosis.

PMID- 23865146
TI  - Thoracic endometriosis syndrome with bloody pleural effusion in a 28 year old
      woman.
AB  - Thoracic endometriosis, rarely encountered, is characterized with the
      localization of functional endometrium tissue in pleura, lung parenchyma or
      tracheobronchial system. A 28 years old female patient visited our clinic with
      complaints of cough and shortness of breath for the last two months. Right-sided
      massive pleural effusion was detected in the chest radiography and thorax
      computed tomography. Exudative fluid was aspirated with a haemorrhagic appearance
      on thoracentesis. Cytology was evaluated as suspicious. "Signet ring cells" were
      reported in pleural biopsy. Diagnostic biopsy was performed by video-assisted
      thoracic surgery (VATS) on the patient whose fiber-optic bronchoscopy was normal.
      The histopathological diagnosis was reported as "pleural endometriosis". Chemical
      pleurodesis was applied with asbestos-free chalk. The thorax HRCT (high
      resolution computed tomography) performed during menstruation was normal.
      Thoracentesis was needed 3 times for recurrent pleural effusion in the follow-ups
      and then parietal pleurectomy was performed. The patient is in postoperative 10th
      month follow-up and evaluated as normal clinically and as radiologically. Pleural
      endometriosis should be considered as a differential diagnosis in female patients
      with infertility with chest symptoms. Video-assisted thoracoscopic surgery can be
      useful in the diagnosis and treatment of these patients and chemical pleurodesis
      and parietal pleurectomy should be considered among the treatment options.

PMID- 23865148
TI  - Failed percutaneous mitral commisurotomy due to congenital anomaly of inferior
      vena cava.
AB  - Since its inception in 1982, percutaneous transvenous mitral commissurotomy
      (PTMC) has gained increasingly wide use internationally in patients with
      Rheumatic Mitral stenosis. PTMC offers an alternative to surgery in patients who
      have pliable mitral valve.Very few reasons were reported to abort the procedure
      when patient lies on the table. This study presents two case reports in which
      congenital venous anomalies were one of the reasons to terminate the procedure.

PMID- 23865149
TI  - Anaesthetic management of craniotomy for intracranial lesion in a child with
      uncorrected tetrology of fallot.
AB  - The case of a 16 years old female with uncorrected Tetrology of Fallot, who
      operated for intracranial lesion in parieto frontal area with midline shift is
      presented. She had right ventricular hypertrophy, clubbing, central and
      peripheral cyanosis. Patient was anaesthetized keeping all measures required to
      avoid haemodynamic swings, tachycardia, desaturation, acidosis and dehydration.
      Pre-operative antibiotic cover was given to prevent bacterial endocarditis.
      Neurosurgeon, Paediatric cardiologist, Anaesthesiologist and Intensivist were
      involved in the preoperative planning and management of the patient.
      Haemodynamics were maintained and managed by monitoring continuous arterial line
      secured pre-induction and central line after induction. During surgery pain was
      controlled with fentanyl boluses intraoperatively and post operatively by
      tramadol infusion. Patient was extubated post operatively in the recovery room
      fulfilling the extubation criteria. She remained haemodynamically stable
      throughout the course. She was discharged on 5th post operative day from the
      hospital on SpO2 of 70-80% at room air.

PMID- 23865150
TI  - Primary skeletal muscle tuberculosis at an unusual site.
AB  - Tuberculosis can involve virtually any organ and it manifests itself in various
      forms. The selective involvement of muscles by a tuberculous process without
      coexisting active skeletal or extraskeletal tuberculosis is very rarely seen. A
      case of isolated tuberculosis of the biceps brachii muscle without any evident
      primary focus revealed as an intramuscular mass in a 37 years old immunocompetent
      female is presented. Diagnosis was established by histology and acid fast stain
      culture. The patient showed marked improvement with a standard four drug regimen
      with no evidence of disease activity at the four year follow up. This rare case
      is presented with review of literature.

PMID- 23865151
TI  - What are the new therapeutic alternatives to warfarin in atrial fibrillation?

PMID- 23865152
TI  - Impact factor of Pakistani medical journals.

PMID- 23865153
TI  - Developmental milestones: even the physicians don't know enough and what we need
      to do?

PMID- 23865154
TI  - Juvenile nasopharyngeal angiofibroma: experience at a tertiary care centre in
      Pakistan.
AB  - OBJECTIVE: To review the clinical presentations of Juvenile nasopharyngeal
      angiofibroma surgical approaches used and outcomes of patients at an urban
      tertiary care centre in Pakistan. METHOD: The retrospective study was conducted
      at Aga Khan University Hospital, Karachi, involving medical records of patients
      with histologically confirmed Juvenile nasopharyngeal angiofibroma who were
      treated between 2000 and 2008. RESULTS: Eighteen male patients were identified,
      with an average age at diagnosis of 16 5.6 (range 11-28) years. Most patients (n
      = 16; 88.9%) presented with epistaxis. CT scan was the most common (n = 17;
      94.44%) radiological investigation for staging. Blood supply of the tumour was
      varied (ipsilateral or bilateral internal maxillary artery). According to Andrews
      staging, 4 (22.22%) patients presented with stage I disease; 5 (27.77%) with
      stage II; 4 (22.22%) with stage IIIa; 1 (5.55%) with stage IIIb; and 4 (22.22%)
      with stage IVb disease. Of the 18 patients, 17 (94.44%) underwent 19 surgical
      procedures, with a recurrence rate of 10.5% (n=2) and incomplete resection in
      15.8% (n = 3) procedures. Lateral rhinotomy was the most frequently employed (n =
      13; 68.42%) surgical approach in the 19 surgical procedures conducted at the
      AKUH. CONCLUSION: Surgery continues to be the mainstay treatment modality.
      Surgical approach is dependent on various disease factors as well as
      institutional resources. In situations of limited resources, the condition may
      still be managed effectively with traditional approaches that result in good
      functional outcome and low morbidity.

PMID- 23865155
TI  - Occupational hazards, illness and injuries faced by child labourers.
AB  - OBJECTIVE: To assess hazards, injuries and illnesses faced by child labourers in
      their working environment. METHODS: The cross-sectional study was conducted in a
      squatter settlement in Sultanabad, Karachi, in January and February, 2011. A
      total of 190 children, aged 9-14 years were interviewed through structured pre
      tested questionnaire at their workplaces. They were asked about their health,
      illness, working hours, frequency of work related illness, frequency and severity
      of injuries they received during work and various other associated factors. SPSS
      17 was used for statistical analysis. RESULTS: The mean age of the children was
      12.60 +/- 1.47 years. Of the total, 140 (78.4%) said they had got injured while
      working during preceding 3 months; 64 (33.7%) had high frequency of injuries; 13
      (6.8%) had severe and 59 (30.6%) had moderate type of injuries; 114 (60.0%) said
      their illness was 'sometimes' work-related or due to the working environment; 159
      (83.2%) were unaware of the occupational hazards they were facing; and 142
      (74.7%) had no adult supervision at work. A significant association was found
      between the occupational related illnesses and the working environment of the
      participants (p = 0.03). CONCLUSION: Majority of the child labourers were found
      to be facing unsafe working conditions, and encountered frequent work-related
      injuries and illnesses.

PMID- 23865156
TI  - Effects of inflow of inpatients attendants at a tertiary care hospital--a study
      at civil hospital Karachi.
AB  - OBJECTIVE: To assess the trend of attendants accompanying inpatients and its
      effect on a tertiary care hospital in Karachi. METHODS: A cross sectional study
      was carried out at CHK, through interview-based questionnaires targeting three
      groups of interest viz. patients admitted in the wards and stable enough to
      answer questions appropriately, attendants residing at CHK premises and heads of
      hospital departments or administrative Resident Medical Officers. RESULTS: Out of
      281 patients, 149 (53.03%) had only one attendant staying with them, 74 (26.34%)
      had two, 39 (13.88%) had more than two and 19 (6.76%) had none. Out of 240
      attendants, 204 (85%) planned to stay within the hospital till discharge of their
      patient while 24 (10%) till a week and 12 (5%) for two weeks. Out of 21
      administrative heads, 18 (85.71%) faced problems due to presence of extra
      attendants and 3 (14.29%) did not. However, all 21 (100%) agreed that there were
      risks associated with presence of too many attendants; which were financial
      burden 13 (61.9%), infections 14 (66.67%), physical violence 11 (52.38%),
      disturbance of hospital sanctity 13 (61.91%), and crimes 10 (47.62%). CONCLUSION:
      Our study suggested that there was a significant trend for patients to be
      accompanied by multiple attendants at CHK. Although hospital did not have to
      provide food and shelter to them, but their presence in large numbers was in
      violation to hospital protocols. In view of the hospital administration multiple
      attendants caused hindrance in duties of staff and posed infections and security
      risks.

PMID- 23865157
TI  - Rare and unusual metastases of a gastrointestinal stromal tumour.
AB  - Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours
      of the gastrointestinal tract, histological and immunohistochemistry findings
      help to differentiate such tumours from other gastrointestinal malignancies.
      Metastasis is common to the stomach and small bowel and often presents with
      gastrointestinal bleeding. This is a case of an 82 year old man with an inguinal
      mass that following exploratory examination was found on histology to be a GIST
      metastases, imaging also showed pulmonary metastases. Following colonoscopy the
      primary caecal mass was found. Such metastatic presentations are extremely rare
      for this type of tumour. This case report highlights these unusual findings.

PMID- 23865158
TI  - Young people with aging ears: a consequence of early presbycusis due to earphones
      misuse.

PMID- 23865159
TI  - Burn injuries and women: a public health concern.

PMID- 23865160
TI  - Factitious disorders and implications for emergency health services.

PMID- 23865161
TI  - Academic practices and research: current scenario and remedial measures.

PMID- 23865162
TI  - MAIL: mining sequential patterns with wildcards.
AB  - Sequential pattern mining is an important research task in many domains, such as
      biological science. In this paper, we study the problem of mining frequent
      patterns from sequences with wildcards. The user can specify the gap constraints
      with flexibility. Given a subject sequence, a minimal support threshold and a gap
      constraint, we aim to find frequent patterns whose supports in the sequence are
      no less than the given support threshold. We design an efficient mining algorithm
      MAIL. Two pattern growth strategies are proposed to improve the completeness and
      the time efficiency. One is based on the candidate occurrence pruning, and the
      other uses an occurrence graph. A random data generator is designed to test the
      completeness on artificial data. Experiments on DNA sequences show that MAIL
      mines four times more patterns than one of its peers and the time performance is
      six times faster on average than its another peer. We also give a concrete
      example in which our algorithm is applied on DNA sequences to find interesting
      patterns.

PMID- 23865163
TI  - Comparison of methods for the selection of genomic biomarkers.
AB  - In recent years, a lot of attention is placed on the selection and evaluation of
      biomarkers in microarray experiments. Two sets of biomarkers are of importance,
      namely therapeutic and prognostic. The therapeutic biomarkers would give us
      information on the response of the genes to treatment in relation to the response
      of the clinical outcome to the same treatments, whereas the prognostic biomarkers
      enable us to predict the clinical outcome irrespective of treatments and other
      confounding factors. In this paper, we use different methods that allow for both
      linear and non-linear associations to select prognostic markers for depression,
      the response.

PMID- 23865164
TI  - A multi-index ROC-based methodology for high throughput experiments in gene
      discovery.
AB  - We address the problem of ranking differentially expressed genes in high
      throughput experiments using Receiver Operating Characteristic (ROC) curves. As
      it is generally unknown whether large expression values constitute 'positive' or
      'negative' results or which group is 'healthy' or 'diseased', we generate four
      ROC curves per gene. We then consider classification indices based on all or part
      of the four ROC curves and identify genes ranked low by the area under the curve
      (AUC) but high by at least one alternative index, invariably resulting to the
      discovery of genes that would otherwise be missed by the AUC index.

PMID- 23865166
TI  - The significance of molecular mechanics property to protein evolution.
AB  - In the study of protein homology, multiple physical systems that correspond to
      different proteins must be jointly considered, such that the similarity of
      homologs can be explained in an aspect of the physics. Compared with the
      investigations that focus on the character of certain protein, the research
      object changes from one physical system to a set of systems. For this enlarged
      object, the importance of different physical quantities is still unclear. In an
      aspect of hydrophobic interaction, we rank the significance of different physical
      quantities here, according to their contribution to the conservation of family
      representative biological properties in protein evolution. Molecular mechanics
      property is suggested to be the governing factor responsible for protein
      homology.

PMID- 23865165
TI  - A clustering approach for estimating parameters of a profile hidden Markov model.
AB  - A Profile Hidden Markov Model (PHMM) is a standard form of a Hidden Markov Models
      used for modeling protein and DNA sequence families based on multiple alignment.
      In this paper, we implement Baum-Welch algorithm and the Bayesian Monte Carlo
      Markov Chain (BMCMC) method for estimating parameters of small artificial PHMM.
      In order to improve the prediction accuracy of the estimation of the parameters
      of the PHMM, we classify the training data using the weighted values of sequences
      in the PHMM then apply an algorithm for estimating parameters of the PHMM. The
      results show that the BMCMC method performs better than the Maximum Likelihood
      estimation.

PMID- 23865167
TI  - Concurrent analysis of copy number variation and gene expression: application in
      paired non-smoking female lung cancer patients.
AB  - Recent studies indicate that both genomic alterations and transcriptional
      dysregulation influence the disease progresses. This study proposes a method
      identifying pathways by integrating copy numbers (CN), gene expressions (GE) and
      their correlations. A lung cancer patients dataset with both normal and tumor
      tissues is utilized to evaluate the performance of the proposed method. To
      further appraise the predicting abilities of those pathways, these patients are
      classified by support vector machines. Based on the classification results,
      pathways integrating CN, GE and their correlations is more informative and
      biologically meaningful and perform better than pathways obtained by only CN or
      only GE.

PMID- 23865168
TI  - A supervised approach to detect protein complex by combining biological and
      topological properties.
AB  - Protein biochemical functions are revealed in the form of protein complexes from
      the Protein-Protein Interaction (PPI) network. In this paper, we propose a
      supervised based algorithm by combining biological and topological properties to
      detect protein complexes in PPI networks, in which protein amino acid background
      frequency is introduced as biological properties and become a new block of the
      features. In comparison with other established methods, the evaluation results
      indicate that the applied method can achieve comparable performances and match
      more meaningful real complexes. We also demonstrate that the use of protein amino
      acid background frequency and the SVM based method can efficiently improve the
      performance.

PMID- 23865169
TI  - Effect of chemical additives on Bacillus thuringiensis (Bacillales: Bacillaceae)
      against Plutella xylostella (Lepidoptera: Pyralidae).
AB  - To examine the effect of chemical additives on Bacillus thuringiensis (Berliner)
      against Plutella xylostella (L.), inorganic salts, nitrogenous compounds, protein
      solubilizing agents, and organic acids were selected and tested. The chosen
      materials are low in cost and environmentally safe. Results show that many
      inorganic salts can increase the activity of B. thuringiensis in a range of 1.31-
      to 3.08-fold. These include calcium acetate, calcium chloride, calcium hydroxide,
      calcium sulfate, calcium carbonate, sodium carbonate, sodium acetate, potassium
      hydroxide, potassium carbonate, potassium acetate, magnesium chloride, magnesium
      sulfate, and zinc sulfate. Nitrogenous compounds, including peptone, sodium
      nitrate, and ammonium nitrate, can enhance the activity of B. thuringiensis 1.62
      , 1.32-, and 1.37-fold, respectively. Among the protein solubilizing agents,
      EDTA, urea, mercaptoethanol and dipotassium hydrogen phosphate increased the
      activity of B. thuringiensis 1.62- to 2.34-fold. Among the organic acids, maleic
      and citric acids boosted the activity 1.45- and 1.55-fold, respectively.
      Meanwhile, sodium benzoate and resorcinol led to 1.74- and 1.44-fold activity
      gains, respectively. Use of appropriate additives could provide great benefit not
      only in reducing the costs for field applications of biological insecticides but
      also by boosting the efficacy of B. thuringiensis.

PMID- 23865170
TI  - A fluctuating thermal regime improves long-term survival of quiescent prepupal
      Megachile rotundata (Hymenoptera: Megachilidae).
AB  - The alfalfa leafcutting bee Megachile rotundata (F.) is the primary pollinator
      for alfalfa seed production. Under standard management conditions, the alfalfa
      leafcutting bee develops to the diapausing prepupal stage under field conditions,
      after which they are cold-stored at a static temperature until the following
      spring, when temperatures are raised and development resumes. We have assessed
      the effects of a fluctuating thermal regime (FTR) during overwintering cold
      storage, where bees were exposed to a daily 1 h pulse of 20 degrees C, and
      compared viability and insect quality to bees stored under a static thermal
      regime. Our results demonstrate that implementing an FTR protocol dramatically
      increases the survival of cold-stored alfalfa leafcutting bees, effectively
      extending their shelf-life into the subsequent growing season. These findings
      could substantially ameliorate significant obstacles that restrict the more
      widespread use of this important pollinator, such as the biological constraints
      that restrict its use in early blooming crops, and yearly fluctuations in bee
      prices that add significant financial uncertainty to end users. This study also
      strengthens a growing body of evidence that indicates FTR protocols are superior
      to static thermal regime protocols for insect cold storage.

PMID- 23865171
TI  - Effects of extended prepupal storage duration on adult flight physiology of the
      alfalfa leafcutting bee (Hymenoptera: Megachilidae).
AB  - The alfalfa leafcutting bee, Megachile rotundata (F.), is a solitary, cavity
      nesting bee and is the primary pollinator for alfalfa seed production. Bee
      management practices include cold storage during the prepupal stage. Fluctuating
      thermal regimes during cold storage increases survival of cold storage and allows
      a doubling of the cold storage period with no decrease in survival. However,
      survival, characterized as successful adult emergence, is not qualitative. In
      this study, we determined whether extended storage affects adult bee respiration
      or flight physiology. We overwintered bees for a single winter (current
      management protocol) or for 12 mo longer (extended storage). We used resting and
      tethered flight metabolic rates and resting critical PO2 (the oxygen partial
      pressure below which metabolism can no longer be sustained) as indices of adult
      bee quality. We found no significant differences in body mass, resting or flight
      metabolic rates, or critical PO2 between the two groups. Together these data
      indicate that extended storage of M. rotundata produces bees of similar
      respiratory capacity and flight ability. These findings could increase the use of
      M. rotundata as an alternative pollinator, allowing for extended storage to time
      adult emergence with early blooming crops.

PMID- 23865172
TI  - Different toxicity of the novel Bacillus thuringiensis (Bacillales: Bacillaceae)
      strain LLP29 against Aedes albopictus and Culex quinquefasciatus (Diptera:
      Culicidae).
AB  - Bacillus thuringiensis (Bt) (Berliner) strain LLP29 produces a crystal protein
      Cyt1Aa6 toxic to mosquito vectors of human diseases. However, the susceptibility
      of Culex quinquefasciatus (Say) in the current study was 8.25 times higher than
      that of Aedes albopictus (Skuse) with this single protein Cyt1Aa6 purified from
      LLP29. To understand the mechanism of the novel mosquitocidal protein, the
      binding characteristic of brush border membrane vesicles from the two tested
      mosquitoes was investigated. Enzyme-linked immunosorbent assay showed that
      Cyt1Aa6 bound to the two mosquitoes' brush border membrane vesicles. However, the
      titer of Ae. albopictus was a little higher than that of Cx. quinquefasciatus,
      with 3.21 and 2.91, respectively. Ligand Western blot analysis showed Cyt1Aa6
      toxin specifically bound to the same three proteins (i.e., 68, 54, and 26 kDa) in
      the two mosquitoes, but one another protein, approximately to 37 kDa, could just
      be detected in Cx. quinquefasciatus. However, little difference was found in the
      test of immunohistochemistry. Cyt1Aa6 was detected in the midguts of both
      mosquitoes with histopathological changes. It would of great importance to the
      knowledge of the novel toxin against to Cx. quinquefasciatus and Ae. albopictus.

PMID- 23865173
TI  - Modeling the integration of parasitoid, insecticide, and transgenic insecticidal
      crop for the long-term control of an insect pest.
AB  - The tools of insect pest management include host plant resistance, biological
      control, and insecticides and how they are integrated will influence the
      durability of each. We created a detailed model of the population dynamics and
      population genetics of the diamondback moth, Plutella xylostella L., and its
      parasitoid, Diadegma insulare (Cresson), to study long-term pest management in
      broccoli Brassica oleracea L. Given this pest's history of evolving resistance to
      various toxins, we also evaluated the evolution of resistance to transgenic
      insecticidal Bt broccoli (expressing Cry1Ac) and two types of insecticides.
      Simulations demonstrated that parasitism provided the most reliable, long-term
      control of P. xylostella populations. Use of Bt broccoli with a 10% insecticide
      free refuge did not reduce the long-term contribution of parasitism to pest
      control. Small refuges within Bt broccoli fields can delay evolution of
      resistance > 30 generations if resistance alleles are rare in the pest
      population. However, the effectiveness of these refuges can be compromised by
      insecticide use. Rainfall mortality during the pest's egg and neonate stages
      significantly influences pest control but especially resistance management. Our
      model results support the idea that Bt crops and biological control can be
      integrated in integrated pest management and actually synergistically support
      each other. However, the planting and maintenance of toxin-free refuges are
      critical to this integration.

PMID- 23865174
TI  - Efficacy of entomopathogenic Steinernema and Heterorhabditis nematodes against
      white grubs (Coleoptera: Scarabaeidae) in peanut fields.
AB  - The efficacy of entomopathogenic nematodes (EPNs) against the white grub
      Holotrichia parallela Motschulsky (Coleoptera: Scarabaeidae) in the peanut
      (Arachis hypogaea L.) fields was evaluated. In the first experiment with a high
      initial white grub population (24.65 +/- 2.44 larvae per m2) in the field,
      Steinernema longicaudum X-7 and Heterorhabditis bacteriophora H06 at 10,000 and
      5,000 infective juveniles (IJs) per plant contributed to significantly higher
      percentage reduction of the white grub larvae, lower percentage of the injured
      legume, and higher peanut yield compared with chlorpyrifos and other treatments.
      The peanut yields harvested from the plots treated with EPNs at 5,000 IJs per
      plant were at least 70% higher than that from the untreated control (water) and
      at least 30% higher than that from chlorpyrifos-treated plots. In the second
      experiment with a low initial white grub population (8.07 +/- 1.29 larvae per m2)
      in the field, EPN treatment did not increase peanut yield compared with the other
      treatments. But both S. longicaudum X-7 and H. bacteriophora H06 gained higher
      percentage reduction of the white grub larvae and lower percentage of the injured
      legume than Steinernema carpocapsae (Weiser) All and the control. The cost
      benefit of using EPNs for white grub control was estimated to be comparable with
      that of using chemicals. S. longicaudum X-7 and H. bacteriophora H06 showed
      promise for white grub control in peanut fields.

PMID- 23865175
TI  - Biocontrol of Bactrocera oleae (Diptera: Tephritidae) with Metarhizium brunneum
      and its extracts.
AB  - The susceptibility of preimaginal and adult olive fruit fly, Bactrocera oleae
      (Gmelin) (Diptera: Tephritidae), to a strain of the mitosporic ascomycete
      Metarhizium brunneum (Petch) (Hypocreales: Clavicipitaceae) and the insecticidal
      activity of its crude extract to olive fruit fly adults were investigated. Strain
      EAMb 09/01-Su caused 60% mortality to B. oleae adults, with average survival time
      (AST) of 8.8 d. In soil treatments against pupariating third-instar larvae,
      preimaginal B. oleae mortality reached 82.3%, whereas preimaginal mortality
      targeting puparia was 33.3%. The crude extract of EAMb 09/01-Su strain caused
      80.0% adult mortality when administered per os, with AST of 27.7 h. The crude
      extract was demonstrated to be quite thermostable and photoresistant. These
      results indicate that M. brunneum EAMb 09/01-Su strain and its crude extract show
      potential to be used in an integrated pest management olive fruit fly management
      strategy targeting both adults and preimaginals.

PMID- 23865176
TI  - Comparing effects of insecticides on two green lacewings species, Chrysoperla
      johnsoni and Chrysoperla carnea (Neuroptera: Chrysopidae).
AB  - This study compared lethal and sublethal effects of five insecticides,
      chlorantraniliprole, cyantraniliprole, spinetoram, novaluron, and lambda
      cyhalothrin, on adult and second instars of two green lacewing species,
      Chrysoperla carnea (Stephens) and Chrysoperla johnsoni Henry, Wells and Pupedis
      (Neuroptera: Chrysopidae) in the laboratory. Formulated pesticides were tested
      using concentrations equivalent to the high label rate dissolved in 378.5 liters
      of water. Novaluron and lambda-cyhalothrin were toxic to larvae and no treated
      larvae survived to the adult stage. Larva to adult survival was reduced in
      chlorantraniliprole, cyantraniliprole, and spinetoram treatments. Larva to adult
      developmental time and sex ratio were not different among the treatments within a
      species. Chlorantraniliprole, cyantraniliprole, spinetoram, and lambda
      cyhalothrin treatments were highly toxic to adults of both species. C. johnsoni
      females had lower fecundity than C. carnea females in the control. Fecundity of
      females was similar in the control and novaluron treatment within each species.
      However, fertility and egg viability were negatively impacted for both species
      when females were treated with novaluron. C. carnea females had higher fertility
      and egg viability than C. johnsoni females in the control. Adults of both species
      had similar longevity in the control and novaluron treatment and adult longevity
      was not gender specific. All insecticides tested were toxic to C. johnsoni and C.
      carnea either at the immature or adult stage or both. Results of this study
      demonstrate a similarity between C. johnsoni and C. carnea for pesticide toxicity
      irrespective of their varied geographical distributions.

PMID- 23865177
TI  - Intraspecific variation of host plant and locality influence the lepidopteran
      parasitoid system of Brassica oleracea crops.
AB  - The aim of the study was to investigate the attractiveness to herbivores and
      parasitoids of two cultivars of Brassica oleracea L., namely, B. oleracea variety
      acephala (kale) and B. oleracea variety capitata (cabbage), that exhibit
      differences of morphological and biochemical traits. To this end, field samplings
      were replicated at seven localities in Galicia (northwestern Spain). Three
      specialist and three generalist lepidopteran species were sampled. In total,
      7,050 parasitoids were obtained, belonging to 18 genera and 22 species. The
      results showed that 1) parasitism rate and parasitoid species richness changed
      with locality and was higher in cabbage, although this crop had lower herbivore
      abundance; 2) the proportion of specialist herbivores was higher in cabbage
      crops, whereas generalists dominated in kale crops; 3) the abundance of the
      parasitoids Telenomus sp. (Hymenoptera, Scelionidae), Cotesia glomerata L.
      (Hymenoptera: Braconidae), and Diadegma fenestrale (Holmgren) (Hymenoptera:
      Ichneumonidae) was higher in kale crops; and 4) parasitism rate of Pieris rapae
      larvae and pupae and Mamestra brassicae eggs were higher in kale crops. In
      contrast with the notion that plant structural complexity provides physical
      refuge to the hosts and can interfere with parasitoid foraging, parasitism rate
      was higher on cabbage plants, which form heads of overlapped leaves. Possibly,
      different chemical profiles of cultivars also influenced the host-parasitoid
      relationship. These results suggest that top-down and bottom-up forces may
      enhance cabbage crops to better control herbivore pressure during the studied
      season. In Spain, information on natural occurring parasitoid guilds of Brassica
      crops is still scarce. The data provided here also represent a critical first
      step for conservation biological control plans of these cultivations.

PMID- 23865178
TI  - Establishment and abundance of Tetrastichus planipennisi (Hymenoptera:
      Eulophidae) in Michigan: potential for success in classical biocontrol of the
      invasive emerald ash borer (Coleoptera: Buprestidae).
AB  - Tetrastichus planipennisi Yang is a gregarious larval endoparasitoid native to
      China and has been introduced to the United States since 2007 for classical
      biological control of the invasive emerald ash borer, Agrilus planipennis
      Fairmaire, an exotic beetle responsible for widespread ash mortality. Between
      2007-2010, T. planipennisi adults (3,311-4,597 females and approximately 1,500
      males per site) were released into each of six forest sites in three counties
      (Ingham, Gratiot, and Shiawassee) of southern Michigan. By the fall of 2012, the
      proportion of sampled trees with one or more broods of T. planipennisi increased
      to 92 and 83% in the parasitoid-release and control plots, respectively, from 33
      and 4% in the first year after parasitoid releases (2009 fall for Ingham county
      sites and 2010 for other sites). Similarly, the mean number of T. planipennisi
      broods observed from sampled trees increased from less than one brood per tree in
      the first year after parasitoid releases to 2.46 (at control plots) to 3.08 (at
      release plots) broods by the fall of 2012. The rates of emerald ash borer larval
      parasitism by T. planipennisi also increased from 1.2% in the first year after
      parasitoid releases to 21.2% in the parasitoid-release plots, and from 0.2 to
      12.8% for the control plots by the fall of 2012. These results demonstrate that
      T. planipennisi is established in southern Michigan and that its populations are
      increasing and expanding. This suggests that T. planipennisi will likely play a
      critical role in suppressing emerald ash borer populations in Michigan.

PMID- 23865179
TI  - Postharvest treatment of fresh fruit from California with methyl bromide for
      control of light brown apple moth (Lepidoptera: Tortricidae).
AB  - Methyl bromide (MB) chamber fumigations were evaluated for postharvest control of
      light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae),
      in fresh fruit destined for export from California. To simulate external feeding,
      larvae were contained in gas-permeable cages and distributed throughout loads of
      peaches, plums, nectarines (all Prunus spp.), apples (Malus spp.), raspberries
      (Rubus spp.), or grapes (Vitis spp.). Varying the applied MB dose and the
      differential sorption of MB by the loads resulted in a range of exposures,
      expressed as concentration x time cross products (CTs) that were verified by gas
      chromatographic quantification of MB in chamber headspace over the course of each
      fumigation. CTs > or = 60 and > or = 72 mg liter(-1) h at 10.0 +/- 0.5 and 15.6
      +/- 0.5 degrees C (x +/- s, average +/- SD), respectively, yielded complete
      mortality of approximately 6,200 larvae at each temperature. These confirmatory
      fumigations corroborate E. postvittana mortality data for the first time in
      relation to measured MB exposures and collectively comprise the largest number of
      larval specimens tested to date. In addition, akinetic model of MB sorption was
      developed for the quarantine fumigation of fresh fruit based on the measurement
      of exposures and how they varied across the fumigation trials. The model
      describes how to manipulate the applied MB dose, the load factor, and the load
      geometry for different types of packaged fresh fruit so that the resultant
      exposure is adequate for insect control.

PMID- 23865180
TI  - Survival of Hessian fly (Diptera: Cecidomyiidae) puparia exposed to simulated hay
      harvest conditions, location and windrow drying in Washington and California.
AB  - Hessian fly, Mayetiola destructor (Say) (Diptera: Cecidomyiidae) puparia are of
      regulatory concern in exported hay, and drying after harvest was evaluated as a
      cultural control technique for bales shipped from the western states. In total
      16,836; 31,122; and 48,051 puparia were tested under drying conditions in
      environmental chambers, open air on location, and hay windrows, respectively.
      Regression lines for percentage of total adults emerging from puparia exposed to
      simulated drying conditions for 1-7 d in environmental chambers was significant
      for 1 September, Kittitas Valley, WA; 3 June, East Columbia Basin, WA; 15 May and
      15 July, San Joaquin Valley, CA; and 15 May, 20 July, and 15 September, Imperial
      Valley, CA. In open air drying on location for 1-7 d, total percentage of puparia
      surviving to adults for all exposure days was 0.4% for 18 June, Kittitas Valley;
      1.2% for 15 May, San Joaquin Valley; and 0% for 16 July, Imperial Valley; and
      significantly different between controls and exposure durations. In hay windrow
      drying for 1-6 d, total percentage of puparia surviving to adults for all
      exposure days was 5.4% on 28 June and 24.2% on 7 September in timothy, Phleum
      pretense, in the Kittitas Valley; 3.8% on 28 June in timothy in the East Columbia
      Basin; 2.2% on 20 July in alfalfa, Medicago sativa, in the San Joaquin Valley;
      and 6.3% on 21 July in Sudan grass, Sorghum bicolor sudanensis, in the Imperial
      Valley. The number of puparia surviving to adults in open air drying and in
      windrows was significantly different between controls and exposure durations for
      all test dates and locations. Puparial survival in field tests was related to
      mild temperatures and high humidities. Hay drying with subsequent field baling,
      storage, and export bale compression is discussed in relation to a systems
      approach for quarantine control of Hessian fly in exported hay.

PMID- 23865181
TI  - Potential for hypobaric storage as a phytosanitary treatment: mortality of
      Rhagoletis pomonella (Diptera: Tephritidae) in apples and effects on fruit
      quality.
AB  - The efficacy of low-oxygen atmospheres using low pressure, referred to as
      hypobaric conditions, to kill egg and third-instar Rhagoletis pomonella (Walsh)
      in apples was investigated. Infested apples were exposed to 3.33 and 6.67 kPa in
      glass jars at 25 and 30 degrees C for times ranging from 3 to 120 h. Probit
      analyses and lethal dose ratio tests were performed to determine differences in
      lethal time values. Eggs were more tolerant of low pressure compared with third
      instar R. pomonella. Mortality of eggs and larvae increased with increase in time
      of exposure to low pressure and temperature. Lower pressures increased percent
      mortality of eggs, but these values were not significantly different at the
      pressures tested in this investigation. The LT99 for R. pomonella eggs at 3.33
      kPa was 105.98 and 51.46 h, respectively, at 25 and 30 degrees C, which was a
      significant effect of the higher temperature on egg mortality. Investigation into
      consumer acceptance of low-pressure-treated apples was done with 'Red Delicious'
      and 'Golden Delicious'. Apples exposed to 3.33 kPa at 25 and 30 degrees C for 3
      and 5 d were stored at 1 degrees C for 2 wk and presented to a sensory panel for
      evaluation. The panelists rated treated apples with untreated controls for
      external and internal appearance and taste. Golden Delicious apples were
      unaffected for all three sensory factors across both temperatures and exposure
      times. Although taste was unaffected for Red Delicious, the internal and external
      appearances deteriorated. Use of low pressure for disinfestation and preservation
      of apples is a potential nonchemical alternative to chemical fumigants such as
      methyl bromide and phosphine.

PMID- 23865182
TI  - Intercepting aliens: insects and mites on budwood imported to South Africa.
AB  - South Africa imports plant budwood (dormant cuttings for propagation) from
      various countries. Phytosanitary measures, including inspections at points of
      entry, are implemented to minimize the chance of a pest being introduced on the
      budwood. This study presents the inspections and interceptions of mites and
      insects on budwood imported to South Africa from 2004 to 2011. The study presents
      crops and countries from which South Africa imports budwood, and gives data on
      the type of imports more often infested with arthropods. Interceptions of insects
      and mites are reported, including interceptions of phytosanitary, economically
      important and nonphytophagous mites. The arthropod taxa intercepted are listed,
      and it is noted that the majority of interceptions are of mites, particularly of
      Eriophyoidea. These data are discussed in the context of quarantine and research.

PMID- 23865183
TI  - Preharvest quarantine treatments of chlorantraniliprole, clothianidin, and
      imidacloprid-based insecticides for control of Japanese beetle (Coleoptera:
      Scarabaeidae) and other scarab larvae in the root zone of field-grown nursery
      trees.
AB  - Japanese beetle, Popillia japonica Newman (Coleoptera: Scarabaeidae), is an
      important quarantine pest of nurseries. Nursery plant movement from P. japonica
      infested regions is regulated by the U.S. Domestic Japanese Beetle Harmonization
      Plan (DJHP), which classifies states by risk categories. Treatments for category
      2 states include preharvest soil surface treatment of nursery plants grown in
      field soil using Discus SC, Marathon (1G or 60 WP), or Flagship (0.22G or 25 WG).
      In this study, Discus, Marathon 60 WP, or Flagship 0.22G DJHP standards were
      compared with labeled rates of non-DJHP-approved insecticides, including
      neonicotinoids clothianidin (Arena 50WDG), generic imidacloprid (Quali-Pro
      Imidacloprid 2 F T&O Insecticide, Mallet 2 F T&O Insecticide, and Lada 2 F
      Insecticide), and imidacloprid + bifenthrin (Allectus SC), as well as the
      anthranilic diamide, chlorantraniliprole (Acelepryn Insecticide). Arena provided
      100% P. japonica control in May, June, and July over four test years, but had one
      larva recovered during August in two of those 4 yr. Acelepryn did not provide
      DJHP-acceptable P. japonica control. During July, Allectus provided 100% P.
      japonica control in three of four test years, but had four larvae in one test
      year. Other treatments tested only during July, which provided 100% P. japonica
      control, included Discus (five tests); Marathon, Quali-Pro, and Mallet (two
      tests); and Lada and Flagship (one test). Generic imidacloprid 2 F formulations
      were equivalent in P. japonica control to DJHP-approved insecticides.
      Insecticides generally performed poorly on other scarabs or curculionid larvae.
      The study supports Arena, Allectus, and generic imidacloprid 2 F products as
      suitable candidates for the DJHP.

PMID- 23865184
TI  - Combination of plant and insect eggs as food sources facilitates ovarian
      development in an omnivorous bug Apolygus lucorum (Hemiptera: Miridae).
AB  - Diet nutrient is considered as an important regulatory factor for reproduction of
      insects. To understand the effect of different food sources on the reproductive
      physiology of Apolygus lucorum (Meyer-Dur), the ovarian development in adult
      females was investigated when they were fed on green beans (Gb), combination of
      green beans Phaseolus vulgaris L and Helicoverpa armigera eggs (GbHe), or H.
      armigera eggs (He). A female of A. lucorum has two ovaries, and each ovary
      contained seven yellowish ovarioles. Females fed on Gb or GbHe had larger ovaries
      and the ovarioles contained larger numbers of oocytes compared with those fed on
      He. Females in GeHe treatment has significantly higher number of follicles per
      ovary throughout the whole adult period compared with those in Gb or He
      treatment. Furthermore, the length of the best developed ovariole was affected by
      the diet type. The females fed on GbHe had the most developed ovarioles, with
      significantly longer ovarioles than those fed on Gb or He. A method was described
      to quantitatively score the degree of ovarian development in the current study.
      Similarly, the ovarian development scores were significantly higher for females
      in GbHe treatment than those in other two diet treatments. The ovarian
      development significantly delayed for females fed on He. Our results demonstrate
      that A. lucorum, as an omnivorous insect species, can acquire nutrients from both
      plant and animal origin food sources, and the combination of plants and animal
      food sources can significantly facilitate the ovary development of its females.

PMID- 23865185
TI  - Compensation of Lygus hesperus induced preflower fruit loss in cotton.
AB  - A 3-yr field study quantified the compensatory ability of cotton (Gossypium
      hirsutum L.) to preflower fruit damage by Lygus hesperus Knight in the Texas High
      Plains under limited irrigation. Experiments were designed to achieve varying
      levels of preflower fruit loss by augmenting Lygus bug populations using nymphal
      bugs reared in a laboratory colony. Treatments included 1) three bugs per plant
      (3PP), 2) one bug per plant (1PP), 3) naturally occurring background bug density
      or untreated control (NC), and 4) 0 bugs achieved through insecticide spray
      applications (SC). Lygus release treatments (3PP and 1PP) were initiated at early
      fruiting (squaring) and repeated weekly for a total of three consecutive weeks.
      Two levels of Lygus bug infestations, one insect per plant (1PP) and three
      insects per plant (3PP), inflicted fruit loss percentages of 24-38 during the
      maximum fruit set period. Observations on the number of fruit lost at the crop
      preharvest stage indicate that plants receiving the 3PP and 1PP treatments
      exhibited higher ability to restrain physiological fruit loss when compared with
      the two control treatments (NC and SC). Cotton plants could not fully compensate
      the yield loss because of fruit damage caused by Lygus bugs at the observed level
      of damage. The total lint yields in the 1PP and 3PP treatments were 114 and 118
      kg/ha lower, respectively, compared with that in treatment SC. The reduction in
      yield was primarily because of the loss of first fruiting position bolls.
      However, lint yields from bolls other than first position of the cotton plant
      were similar across treatments. Fiber quality data indicated an increase in fiber
      length from insect release treatment plants compared with the two control
      treatments.

PMID- 23865186
TI  - Patterns of spatial and temporal distribution of the asparagus miner (Diptera:
      Agromyzidae): implications for management.
AB  - The asparagus miner is an obligatory feeder on asparagus and a putative vector
      for pathogenic fungi implicated in the early decline of asparagus fields. To
      date, the distribution of the asparagus miner over space and time is poorly
      understood. Our study evaluated the spatial and temporal pattern of adult
      asparagus miners in commercial asparagus fields in Michigan in 2011 and 2012. We
      sampled adults and damage weekly during the growing season using yellow sticky
      traps outside, at the edge, and inside commercial fields. Yellow sticky traps at
      each trapping location were placed at the canopy and ground level to determine
      vertical distribution of adults. During the first generation, adults were more
      evenly distributed throughout the field. In the second generation, adults were
      more commonly found on the edge of the field. Overall, there was a greater
      percent of mining damage near the edge of the field. Additionally, three times as
      many asparagus miners were found in the canopy compared with ground-level traps.
      There were 12 times as many asparagus miner adults on edges bordered by another
      asparagus field than on ones bordered by forest. Taken together, our results
      indicate that while asparagus miner management in the beginning of the growing
      season should focus on the entire field, in the latter half of the season,
      growers could save money and resources by targeting miner adults at the edges of
      fields. Finally, conserving the remaining naturally forested landscape and
      planting borders of trees may help ameliorate pest pressure in asparagus fields.

PMID- 23865187
TI  - Effects of pesticides used on citrus grown in Spain on the mortality of Ceratitis
      capitata (Diptera: Tephritidae) Vienna-8 strain sterile males.
AB  - Vienna-8 sterile males are currently released in Spain to reduce wild populations
      of the medfly. Because pesticides are required to maintain populations of some
      citrus key pests below economic thresholds, there is a need to evaluate the
      effects of pesticides commonly used in citrus on Vienna-8 males. Males were
      exposed to differently aged residues of eight pesticides. Abamectin, etofenprox,
      etoxazole, petroleum spray oil, pymetrozine, and pyriproxyfen resulted harmless
      to Vienna-8 males. However, fresh residues of chlorpyrifos and spinosad caused
      high mortalities and had residual effects until 21 and 28 d after treatment,
      respectively. Following the same method, the lethal effects of chlorpyrifos and
      spinosad on Ceratitis capitata (Wiedemann) wild-type (wt) males were determined.
      Surprisingly, these pesticides resulted more toxic for wt than for Vienna-8
      males. To determine whether these results could be attributed to intrinsic
      characteristics of the pesticides or to behavioral differences among Vienna-8 and
      wt males, a topical application trial was conducted. Vienna-8 males were twice as
      susceptible to chlorpyrifos as wt males, whereas their susceptibility to spinosad
      was slightly lower. These results in intrinsic toxicity did not directly explain
      the differences observed in the extended-laboratory tests with these pesticides.
      We hypothesize that the lower flight activity ofVienna-8 males relative to wt
      conspecifics can explain the lower risk observed for Vienna-8 males in the
      residual tests. Our results should be taken into account when planning area-wide
      Sterile Insect Technique programs against C. capitata especially in those areas
      where treatments with chlorpyrifos are approved.

PMID- 23865189
TI  - Corn defense responses to nitrogen availability and subsequent performance and
      feeding preferences of beet armyworm (Lepidoptera: Noctuidae).
AB  - Many studies have reported the effect of nitrogen (N) fertilization on plant
      constitutive defense responses; however, little is known about their effects on
      plant induced defense patterns and its consequence for insect herbivores. In our
      experiments, the effects of N availability on growth, nutritional quality (N
      content, protein/carbohydrate [P:C] ratio, modified gross energy [MGE]), and
      constitutive phenolics of corn, Zea mays L. were quantified. Moreover, the
      indirect effects of N fertilization on the beet armyworm, Spodoptera exigua
      Hubner through larval performance and feeding preference were examined. N
      fertilization increased plant growth, and depressed defense traits by increasing
      N content and the P:C ratio, as well as decreasing the constitutive concentration
      of phenolics. Subsequently, beet armyworm showed higher performance and
      preferentially fed on high-N corn because of its low defense traits. After beet
      armyworm feeding, high-N corn significantly deterred larval feeding, and had
      negative effects on the performance of beet armyworm through decreasing P:C ratio
      and increasing induced phenolics. On the contrary, there were no significant
      changes in P:C ratio and phenolics in low-N corn after feeding damage. Larval
      performance and preference were also not affected by induced compounds in low-N
      corn, which suggested that the expression of induced defense was dependent on N
      availability. The result indicates that N availability can exert a variety of
      bottom-up effect on plant defense patterns to influence insect population
      dynamics, and thereby may represent a source of variation in plant-insect
      interactions.

PMID- 23865188
TI  - Relationship between time to flowering and stalk and ear damage by second
      generation corn borers.
AB  - In the Mediterranean area, the main corn borer species are Sesamia nonagrioides
      Lefebvre (Mediterranean corn borer) and Ostrinia nubilalis Hubner (European corn
      borer). In the overall context of integrated pest control, it is possible to
      reduce the effect of a pest without having a negative effect on the environment
      by varying the sowing date. Benefits are possible if the most susceptible stages
      of the crop no longer coincide with the peak of the pest. We used different
      cycles of selection (0, 6, 8, 10, and 12) of two populations (Purdue A and Purdue
      B) of maize selected for early flowering to get a more precise estimation of the
      relationship between maturity of plant tissues and corn borer damage. We found a
      relationship between the damage produced by corn borers and the number of days
      from flowering to infestation. We conclude that, after flowering, a later stage
      of plant development at the moment of the infestation by corn borers reduces the
      damage caused by the larvae. Based on our results, we recommend to plant as early
      as possible so the tissues would be as mature as possible at the moment of insect
      attack.

PMID- 23865190
TI  - Corn earworm (Lepidoptera: Noctuidae) in northeastern field corn: infestation
      levels and the value of transgenic hybrids.
AB  - Corn earworm, Helicoverpa zea (Boddie), is a polyphagous noctuid pest of
      agricultural crops across the United States that is gaining attention as a pest
      of field corn. Before the introduction of transgenic insect-resistant hybrids,
      this pest was largely ignored in field corn, but now many Bacillus thuringiensis
      (Bt) corn hybrids have activity against corn earworm. However, the value of
      control in the northeastern United States is unclear because the risk posed by
      corn earworm to field corn has not been well characterized. To understand the
      threat from corn earworm and the value of Bt hybrids in field corn, we assessed
      corn earworm injury in Bt and non-Bt hybrids at 16 sites across four maturity
      zones throughout Pennsylvania in 2010, and 10 sites in 2011. We also used corn
      earworm captures from the PestWatch pheromone trapping network to relate moth
      activity to larval damage in field corn. Corn earworm damage was less than one
      kernel per ear at 21 of 26 sites over both years, and the percentage of ears
      damaged was generally < 15%, much lower than in the southern United States where
      damage can be up to 30 kernels per ear. At sites with the highest damage levels,
      Bt hybrids suppressed corn earworm damage relative to non-Bt hybrids, but we
      found no differences among Bt traits. Cumulative moth captures through July
      effectively predicted damage at the end of the season. Currently, the additional
      benefit of corn earworm control provided by Bt hybrids is typically less than
      US$4.00/ha in northeastern field corn.

PMID- 23865191
TI  - Relative influence of plant quality and natural enemies on the seasonal dynamics
      of Bemisia tabaci (Hemiptera: Aleyrodidae) in cotton.
AB  - The abundance and distribution of insect herbivores is determined by, among other
      things, plant quality and natural enemies. These two factors vary temporally and
      spatially, subsequently affecting seasonal population dynamics. The relative
      influence of plant quality and natural enemies on the seasonal dynamics of
      Bemisia tabaci (Gennadius) was investigated in a 3-yr field study in cotton.
      Plant quality was manipulated through varying irrigation regimes: irrigations
      done at 20, 40, and 60% soil water depletions; and natural enemy densities were
      manipulated using broad spectrum insecticide applications that reduced their
      densities compared with unsprayed controls. In each year, densities of B. tabaci
      eggs, large nymphs and adults were consistently higher when natural enemy
      densities were reduced compared with when they were left unaltered, regardless of
      irrigation regime. In contrast, effects of plant quality on densities of all
      whitefly stages were weak and inconsistent. In addition, natural enemy densities
      and predator:prey ratios also were not generally affected by plant quality.
      Interactions between natural enemies and plant quality on whitefly dynamics were
      rare. In general, whitefly densities were elevated two-thirds of the time and
      increased two- to sixfold when natural enemy densities were reduced compared with
      plant quality effects which influenced whitefly densities about one-third of the
      time and were expressed inconsistently over the years. This indicates that
      natural enemies exert a comparatively greater influence on seasonal dynamics of
      B. tabaci in cotton than plant quality, as manipulated by differential
      irrigation.

PMID- 23865192
TI  - Western bean cutworm survival and the development of economic injury levels and
      economic thresholds in field corn.
AB  - Western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), is a
      native pest of dry beans (Phaseolus vulgaris L.) and corn (Zea mays L.).
      Historically, the western bean cutworm was distributed in the western United
      States, but since 1999 eastward expansion has been observed. In corn, economic
      impact is caused by larval ear feeding. Information on western bean cutworm
      biology, ecology, and economic impact is relatively limited, and the development
      of economic injury levels (EILs) and economic thresholds (ETs) is required for
      more effective management. Studies during 2008-2011, across three ecoregions of
      Nebraska, sought to characterize western bean cutworm survival and development of
      EILs and ETs. Calculations of EILs and ETs incorporated the dynamics of corn
      price, management cost, and pest survival. The results from the current study
      demonstrated low larval survival of this species (1.51-12.82%). The mean yield
      loss from one western bean cutworm larva per plant was 945.52 kg/ha (15.08
      bu/acre), based on 74,100 plants per ha. Economic thresholds are expressed as a
      percentage of plants with at least one egg mass. This study is the first study
      that explicitly incorporates variable management costs and crop values into
      western bean cutworm EIL calculations, and larval survival into ET calculations.

PMID- 23865193
TI  - Costs of Lygus herbivory on cotton associated with farmer decision-making: an
      ecoinformatics approach.
AB  - Because the farmer is typically excluded from the experimental research setting,
      experimental research may face challenges in evaluating pest management tactics
      whose costs and benefits hinge on farmer decision-making. In these cases an
      ecoinformatics approach, in which observational data collected from the
      commercial farming setting are "mined" to quantify both biological variables and
      farmer behavior, can complement experimentation as a useful research tool. Here I
      analyze such an observational data set to characterize associations between early
      (June) and mid-season (July) Lygus hesperus Knight populations and farmer
      decisions to apply plant growth regulators and defoliants. Previous experimental
      work suggested the hypothesis that Lygus herbivory, by inducing abscission of
      young flower buds, might generate increased use of plant growth regulators and
      defoliants. Cotton's ability to compensate for loss of flower buds may, however,
      increase as plants grow. On upland cotton, June Lygus populations were associated
      with increased use of plant growth regulators, as expected, but this relationship
      was not observed for July Lygus populations. June Lygus populations were not
      associated with the use of defoliants, whereas, surprisingly, July Lygus
      populations were associated with decreases in defoliant use. In contrast to these
      positive and negative associations observed on upland cotton, on Pima cotton
      Lygus populations exhibited no associations with use of either plant growth
      regulators or defoliants. These results suggest that cotton responses to Lygus
      herbivory, as demonstrated in previously published experimental studies, can
      translate into economically meaningful changes in farmer decisions to apply
      agricultural chemicals.

PMID- 23865194
TI  - Differential performance of Sitobion avenae (Hemiptera: Aphididae) clones from
      wheat and barley with implications for its management through alternative
      cultural practices.
AB  - Cultural control measures should play an important role in cereal aphid
      management on wheat and barley. Planting barley in fields adjacent to those of
      wheat and intercropping wheat with barley are cultural practices that might
      suppress the cosmopolitan cereal pest Sitobion avenae (F.). To evaluate the
      potential effects of these cultural measures on aphid outbreak risks, clones of
      S. avenae were collected from wheat and barley. Host-switch experiments for the
      collected clones were conducted in the laboratory to compare their life table
      parameters and other life history traits. Our results demonstrated that wheat
      clones of S. avenae had lower developmental times, higher fecundities, and higher
      growth rates compared with barley clones when tested on the plant of origin. When
      transferred to barley, the performance of wheat clones was decreased in terms of
      developmental times of nymphs and age at first reproduction of adults. Barley
      clones' performance was decreased in terms of reproductive time or lifespan of
      adult on wheat compared with that on barley. The age-specific survival rates of
      barley clones tended to be lower than wheat clones in the earlier part of their
      lives on wheat. The age-specific fecundity of barley clones on barley remained
      low and fluctuated significantly during their lifetime. Although quite a few
      significant correlations between developmental and reproductive traits were
      identified on both plants, no significantly negative correlations (i.e., trade
      offs) for the traits were found between plants. The results suggested that barley
      clones could be generalized but wheat clones were more specialized to their host
      plant. The potential benefits of the abovementioned cultural measures were
      discussed.

PMID- 23865196
TI  - Single and multiple in-season measurements as indicators of at-harvest cotton
      boll damage caused by verde plant bug (Hemiptera: Miridae).
AB  - The ability to monitor verde plant bug, Creontiades signatus Distant (Hemiptera:
      Miridae), and the progression of cotton, Gossypium hirsutum L., boll responses to
      feeding and associated cotton boll rot provided opportunity to assess if single
      in-season measurements had value in evaluating at-harvest damage to bolls and if
      multiple in-season measurements enhanced their combined use. One in-season verde
      plant bug density measurement, three in-season plant injury measurements, and two
      at-harvest damage measurements were taken in 15 cotton fields in South Texas,
      2010. Linear regression selected two measurements as potentially useful
      indicators of at-harvest damage: verde plant bug density (adjusted r2 = 0.68; P =
      0.0004) and internal boll injury of the carpel wall (adjusted r2 = 0.72; P =
      0.004). Considering use of multiple measurements, a stepwise multiple regression
      of the four in-season measurements selected a univariate model (verde plant bug
      density) using a 0.15 selection criterion (adjusted r2 = 0.74; P = 0.0002) and a
      bivariate model (verde plant bug density-internal boll injury) using a 0.25
      selection criterion (adjusted r2 = 0.76; P = 0.0007) as indicators of at-harvest
      damage. In a validation using cultivar and water regime treatments experiencing
      low verde plant bug pressure in 2011 and 2012, the bivariate model performed
      better than models using verde plant bug density or internal boll injury
      separately. Overall, verde plant bug damaging cotton bolls exemplified the
      benefits of using multiple in-season measurements in pest monitoring programs,
      under the challenging situation when at-harvest damage results from a sequence of
      plant responses initiated by in-season insect feeding.

PMID- 23865195
TI  - Soybean aphid (Aphididae: Hemiptera) population growth as affected by host plant
      resistance and an insecticidal seed treatment.
AB  - The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae) is a
      significant soybean pest in the north central United States. Insecticidal seed
      treatments and host plant resistance are two commercially available management
      tools. Here we investigate the efficacy of both management tools throughout the
      season. Soybean lines containing the soybean aphid resistance genes Rag1, Rag2,
      or both Rag1 + Rag2 were compared with a near-isogenic aphid-susceptible line.
      Each line was grown in field plots both with and without thiamethoxam applied to
      the seed. Individual plants from each plot were caged and infested with soybean
      aphids to measure the efficacy and potential interaction of aphid resistance and
      thiamethoxam. Aphid population growth rate was measured for each caged plant for
      9-12 d after infestation. New cages were established each week from 34 d after
      planting (dap) to 92 dap to track seasonal variations in efficacy. Thiamethoxam
      reduced population growth only at the 42 dap time point and only for the
      susceptible, Rag1, and Rag2 lines. The lack of an effect of thiamethoxam on the
      Rag1 + Rag2 line was likely because of already high mortality from two resistance
      genes. Aphid resistance alone reduced population growth compared with the
      susceptible line at least till 55 dap for single-gene resistance and 63 dap for
      the two genes combined. Aphid resistance provided suppression of soybean aphid
      population growth throughout the season unlike the insecticidal seed treatment.

PMID- 23865197
TI  - Does feeding by Halyomorpha halys (Hemiptera: Pentatomidae) reduce soybean seed
      quality and yield?
AB  - The nonnative brown marmorated stink bug, Halyomorpha halys Stal (Hemiptera:
      Pentatomidae), has become an abundant pest of mid-Atlantic soybean since its
      introduction in the mid-1990s. Currently, there is little information indicating
      how this new pest should be managed in soybean or if economic thresholds
      developed for native stink bugs should be adjusted. In 2010 and 2011, field cage
      studies were conducted in Beltsville, MD, and Suffolk, VA, to evaluate H. halys
      injury to three different soybean reproductive development stages. Cages were
      infested for 2 wk using densities of zero, one, two, four, or eight stink bugs
      (fifth instars and adults) per 0.3 row-m. Cage plots were harvested, and
      subsamples were taken to determine pod losses and seed quality. Feeding injury to
      soybean caused by H. halys was similar to that of native stink bugs, as evidenced
      by seed destruction, punctures, and destroyed pods. Densities of four stink bugs
      per 0.3 row-m resulted in significant seed damage in three of four experiments.
      The full flowering (R2) soybean development stage was least affected by H. halys
      feeding. The full pod (R4) and the full seed (R6) stage were similarly sensitive
      to injury. There was no significant yield loss was associated with stink bug
      densities at either location, although there were significant differences among
      stages in two of four experiments. The data do not indicate that threshold
      densities for H. halys should be different than for the native stink bugs.

PMID- 23865198
TI  - Evaluation of digital photography for quantifying Cryptococcus fagisuga
      (Hemiptera: Eriococcidae) density on American beech trees.
AB  - Beech scale (Cryptococcus fagisuga Lindinger) (Hemiptera: Eriococcidae) is an
      invasive forest insect established in the eastern United States and Canada. It
      predisposes American beech (Fagus grandifolia Ehrhart) trees to infection by
      Neonectria spp. Fungi causing beech bark disease. White wax secreted by the
      diminutive scales obscures individual insects, making it difficult to accurately
      quantify beech scale density. Our goals were to 1) evaluate the relationship
      between the area of wax and number of beech scales on bark samples, 2) determine
      whether digital photos of bark could accurately quantify beech scale density, and
      3) compare efficiency and utility of a qualitative visual estimate and using the
      quantitative digital photo technique to assess beech scale populations. We
      visually estimated beech scale abundance and photographed designated areas on the
      trunk of 427 trees in 40 sites across Michigan. Photos were analyzed using a
      binary threshold technique to quantify the area of beech scale wax on each photo.
      We also photographed and then collected 104 bark samples from 45 additional beech
      trees in ten sites. We removed the wax, counted individual scales on each sample
      using a microscope, and assessed the linear relationship between wax area and
      scale counts. Area of wax explained approximately 80% of the variability in scale
      density. We could typically quantify beech scale density on 15 photographs per
      hour. Qualitative visual assessments of beech scale in the field corresponded
      with estimates derived from photos of bark samples for 79% of trees.

PMID- 23865199
TI  - Effect of temperature and tree species on damage progression caused by
      whitespotted sawyer (Coleoptera: Cerambycidae) larvae in recently burned logs.
AB  - The whitespotted sawyer, Monochamus scutellatus scutellatus (Say) (Coleoptera: Ce
      rambycidae), is one of the most damaging wood-boring insects in recently burned
      boreal forests of North America. In Canada, salvage logging after wildfire
      contributes to maintaining the timber volume required by the forest industry, but
      larvae of this insect cause significant damage that reduces the economic value of
      lumber products. This study aimed to estimate damage progression as a function of
      temperature in recently burned black spruce (Picea mariana (Miller) Britton,
      Sterns, and Poggenburg) and jack pine (Pinus banksiana Lambert) trees. Using
      axial tomographic technology, we modeled subcortical development and gallery
      depth progression rates as functions of temperature for both tree species.
      Generally, these rates were slightly faster in black spruce than in jack pine
      logs. Eggs laid on logs kept at 12 degrees C did not hatch or larvae were unable
      to establish themselves under the bark because no larval development was
      observed. At 16 degrees C, larvae stayed under the bark for > 200 d before
      penetrating into the sapwood. At 20 degrees C, half of the larvae entered the
      sapwood after 30-50 d, but gallery depth progression stopped for approximately 70
      d, suggesting that larvae went into diapause. The other half of the larvae
      entered the sapwood only after 100-200 d. At 24 and 28 degrees C, larvae entered
      the sapwood after 26-27 and 21 d, respectively. At 28 degrees C, gallery depth
      progressed at a rate of 1.44 mm/d. Temperature threshold for subcortical
      development was slightly lower in black spruce (12.9 degrees C) than in jack pine
      (14.6 degrees C) and it was 1 degrees C warmer for gallery depth progression for
      both tree species. These results indicate that significant damage may occur
      within a few months after fire during warm summers, particularly in black spruce,
      which highlights the importance of beginning postfire salvage logging as soon as
      possible to reduce economic losses.

PMID- 23865200
TI  - Impact of early season apical meristem injury by gall inducing tipworm (Diptera:
      Cecidomyiidae) on reproductive and vegetative growth of cranberry.
AB  - Larvae of cranberry tipworm, Dasineura oxycoccana Johnson, disrupt early season
      growth of cranberry (Vaccinium macrocarpon Aiton) uprights or shoots by feeding
      on apical meristem tissue. A 2-yr field study was carried out at three different
      locations to determine the impact of tipworm feeding injury on the reproductive
      and vegetative growth of two cranberry cultivars ('Howes' and 'Stevens') in
      Massachusetts. In addition to tipworm-injured and intact control uprights, an
      artificial injury treatment simulating tipworm feeding was also included.
      Individual uprights of cranberry exhibited tolerance to natural (tipworm) and
      simulated apical meristem injury in the current growing season (fruit production)
      and results were corroborated by a greenhouse study. In the field study, weight
      of fruit was higher in tipworm-injured uprights as compared with intact control
      uprights at the sites with Howes. However, majority of injured uprights (tipworm
      and simulated) did not produce new growth from lateral buds (side-shoots) before
      the onset of dormancy. In the next growing season, fewer injured uprights resumed
      growth and produced flowers as compared with intact uprights at two of the three
      sites. We suggest that multiple-year studies focusing on whole plant response to
      tipworm herbivory will be required to determine the costs of chronic feeding
      injury over time.

PMID- 23865201
TI  - Evaluation of acute toxicity of essential oil of garlic (Allium sativum) and its
      selected major constituent compounds against overwintering Cacopsylla chinensis
      (Hemiptera: Psyllidae).
AB  - In our screening program for insecticidal activity of the essential oils/extracts
      derived from some Chinese medicinal herbs and spices, garlic (Allium sativum L.)
      essential oil was found to possess strong insecticidal activity against
      overwintering adults of Cacopsylla chinensis Yang et Li (Hemiptera: Psyllidae).
      The commercial essential oil of A. sativum was analyzed by gas chromatography
      mass spectrometry. Sixteen compounds, accounting for 97.44% of the total oil,
      were identified, and the main components of the essential oil of A. sativum were
      diallyl trisulfide (50.43%), diallyl disulfide (25.30%), diallyl sulfide (6.25%),
      diallyl tetrasulfide (4.03%), 1,2-dithiolane (3.12%), allyl methyl disulfide
      (3.07%), 1,3-dithiane (2.12%), and allyl methyl trisulfide (2.08%). The essential
      oil of A. sativum possessed contact toxicity against overwintering C. chinensis,
      with an LC50 value of 1.42 microg per adult. The two main constituent compounds,
      diallyl trisulfide and diallyl disulfide, exhibited strong acute toxicity against
      the overwintering C. chinensis, with LC50 values of 0.64 and 11.04 /g per adult,
      respectively.

PMID- 23865202
TI  - Population genetics of invasive Bemisia tabaci (Hemiptera: Aleyrodidae) cryptic
      species in the United States based on microsatellite markers.
AB  - The Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) cryptic species complex
      of whiteflies contains two species, MEAM1 and MED, that are highly invasive in
      supportive climates the world over. In the United States, MEAM1 occurs both in
      the field and in the greenhouse, but MED is only found in the greenhouse. To make
      inferences about the population structure of both species, and the origin and
      recent spread of MED within the United States, 987 MEAM1 whiteflies and 340 MED
      whiteflies were genotyped at six and seven microsatellite loci, respectively, for
      population genetic analyses. Major results of the study are 1) MED exhibits more
      population structure and genetic differentiation than MEAM1, 2) nuclear
      microsatellite markers exhibit a high degree of concordance with mitochondrial
      markers recovering a major east-west phylogeographic break within MED, 3) both
      eastern and western MED are found throughout the continental United States and
      eastern MED is present in Hawaii, and 4) MEAM1 contains two greenhouse U.S.
      populations significantly differentiated from other U.S. MEAM1. The results
      suggest that MED was introduced into the United States on at least three
      occasions and rapidly spread throughout the United States, showing no discernible
      differentiation across 7,000 km. The results further suggest that there is an
      enhanced role of the protected agricultural environment in promoting genetic
      differentiation in both invasive B. tabaci cryptic species.

PMID- 23865203
TI  - Relationship of almond kernel damage occurrence to navel orangeworm (Lepidoptera:
      Pyralidae) success.
AB  - ALaboratory and field studies are reported that assess navel orangeworm (Amyelois
      transitella (Walker)) development and damage on 11 almond varieties that
      represent both expected and outlying hull split and shell seal A. transitella
      damage. Twenty neonate larvae were introduced to almonds of three treatments for
      each variety: scratched (1 mm scratch through the pellicle), shelled (shell
      removed but pellicle intact), and unshelled (shell intact and exhibiting the
      tightest shell seal for the variety). Success was evaluated as moth emergence and
      degree-days (DD) to emergence. In 2010-2011 and 2011-2012, 10 replicate rows
      containing randomized strands of 20 unshelled, uninfested almonds from each
      variety were placed in the field for both the fall and spring A. transitella
      flight. The almonds were returned to the lab before the initiation of the second
      spring A. transitella flight and categorized by presumed cause of damage (bird
      damage, A. transitella damage, or both types of damage). Damage, variety, and
      their interaction significantly impacted A. transitella survival and DDs to
      emergence in male moths. Female moth DDs to emergence were significantly impacted
      by damage alone. Damage from birds and A. transitella damage were positively
      correlated, and A. transitella damage associated with bird damage was more common
      than A. transitella damage alone. Nonconspecific damage may have a significant
      impact on A. transitella populations in the field, and bird damage may have
      repercussions beyond its direct impact on marketable yield.

PMID- 23865204
TI  - Mating behavior of Cnephasia jactatana (Lepidoptera: Tortricidae), an important
      pest of kiwifruit.
AB  - Understanding mating behavioral sequence helps us identify the mechanisms of mate
      assessment and choice, and better evaluate behavior-based pest control
      strategies. Here we describe the mating behavior of Cnephasia jactatana Walker
      whose females release a sex pheromone, and determine the effect of male mating
      status on reproductive success. The mating sequence starts when males approach
      females and display courtship behavior with antennation and fanning wings. Both
      males and females may end a mating attempt at any stage of the sequence. Both
      sexes assess their mates from the initial contact to copulation. Females appear
      to be choosier at the early and mid-stages than at the late stage of the
      sequence. Virgin males approach and court females significantly earlier than
      nonvirgin males. As compared with nonvirgin males, virgin males are approximately
      1.6 times more likely to approach and 1.8 times more likely to court females, and
      four times more likely to achieve mating. This may be attributed to depletion of
      sperm and accessory gland materials and reduced ability to respond to female sex
      pheromones in nonvirgin males. The number of attempts by males to acquire mates
      may be one of the traits that females assess before choosing their mates.

PMID- 23865205
TI  - Effects of high-gossypol cotton on the development and reproduction of Bemisia
      tabaci (Hemiptera: Aleyrodidae) MEAM1 cryptic species.
AB  - Use of plant secondary metabolic compounds is an important method for insect pest
      control. In this study, the survival, development, and reproduction of Bemisia
      tabaci (Gennadius) (Hemiptera: Aleyrodidae) MEAM1 cryptic species were compared
      over two consecutive generations on three cotton cultivars of different gossypol
      levels. Both cotton cultivar and generation significantly affected the fitness of
      the whitefly. In both generations, the immature development times on the low
      gossypol cultivar ZMS13 were significantly longer than those on the high-gossypol
      cultivar M9101 or medium-gossypol cultivar HZ401. The female fecundity and rate
      of population increase of the whitefly ranked in the following order: ZMS13 >
      HZ401 > M9101. On each cultivar, the immature development time was shorter and
      the immature survival rate was higher in the second generation than those in the
      first generation. Rate of increase was also higher in the second generation.
      These results demonstrated that the fitness of B. tabaci MEAM1 cryptic species on
      the low-gossypol cotton cultivar ZMS13 was higher than that on the medium- or
      high-gossypol cultivar. The comparison of the life histories of B. tabaci MEAM1
      cryptic species on different cotton varieties is important for the development of
      an integrated pest management program of the whitefly by using plant secondary
      metabolic compounds.

PMID- 23865206
TI  - Nectar and flower traits of different onion male sterile lines related to
      pollination efficiency and seed yield of F1 hybrids.
AB  - Honey bees are the main pollinators of onion crops for seed production, but owing
      to low attractiveness of flowers, pollination is often inadequate. Pollination
      problems result in low seed yields. This problem is accentuated when male sterile
      lines (MSL) are used to produce hybrid onion seeds. In this study, the effect of
      floral attributes and nectar composition on the preference of honey bees of four
      MSLs and one onion open pollinated cultivar were assessed. The chemical
      composition of nectar was described through the analysis of sugars, trace
      elements, volatile organic compounds, and phenol compounds. The samples studied
      showed qualitative and quantitative differences in the analyzed traits of flowers
      and nectar among the different lines. Furthermore, field observations showed a
      great difference on the number of bee visits and seed yield among the onion lines
      analyzed. For the first time, this study demonstrates that there are marked
      differences in the chemical composition of nectar and floral morphology between
      open pollinated and MSLs and also within MSLs. In addition, these differences
      were correlated with the number of visits and seed yield. Therefore, it would be
      possible to select indirectly the most promising productive MSL using simple
      determinations of chemical compounds or floral morphological characters.

PMID- 23865207
TI  - Ability of field populations of Coptotermes spp., Reticulitermes flavipes, and
      Mastotermes darwiniensis (Isoptera: Rhinotermitidae; Mastotermitidae) to damage
      plastic cable sheathings.
AB  - A comparative field study was conducted to evaluate the ability of subterranean
      termites to damage a set of four different plastic materials (cable sheathings)
      exposed below- and above-ground. Eight pest species from six countries were
      included, viz., Coptotermes formosanus (Shiraki) in China, Japan, and the United
      States; Coptotermes gestroi (Wasmann) in Thailand and Malaysia; Coptotermes
      curvignathus (Holmgren) and Coptotermes kalshoveni (Kemner) in Malaysia;
      Coptotermes acinaciformis (Froggatt) with two forms of the species complex and
      Mastotermes darwiniensis (Froggatt) in Australia; and Reticulitermes flavipes
      (Kollar) in the United States. Termite species were separated into four tiers
      relative to decreasing ability to damage plastics. The first tier, most damaging,
      included C. acinaciformis, mound-building form, and M. darwiniensis, both from
      tropical Australia. The second tier included C. acinaciformis, tree-nesting form,
      from temperate Australia and C. kalshoveni from Southeast Asia. The third tier
      included C. curcignathus and C. gestroi from Southeast Asia and C. formosanus
      from China, Japan, and the United States, whereas the fourth tier included only
      R. flavipes, which caused no damage. A consequence of these results is that
      plastics considered resistant to termite damage in some locations will not be so
      in others because of differences in the termite fauna, for example, resistant
      plastics from the United States and Japan will require further testing in
      Southeast Asia and Australia. However, plastics considered resistant in Australia
      will be resistant in all other locations.

PMID- 23865209
TI  - Detection of resistance, cross-resistance, and stability of resistance to new
      chemistry insecticides in Bemisia tabaci (Homoptera: Aleyrodidae).
AB  - Resistance levels in whitefly, Bemisia tabaci (Gennadius) collections from cotton
      and sunflower (up to four districts) for five neonicotinoids and two insect
      growth regulators (IGRs) were investigated for two consecutive years. Based on
      the LC50(s), all collections showed slight to moderate levels of resistance for
      the tested insecticides compared with the laboratory susceptible population. The
      data also indicated that cotton and sunflower collections had similar resistance
      levels. In comparison (four collections), Vehari collections showed higher
      resistance for acetamiprid, thiacloprid, and nitenpyram compared with those of
      others. Average resistance ratios for acetamiprid, thiacloprid, and nitenpyram
      ranged from 5- to 13-, 4- to 8-, and 9- to 13-fold, respectively. Multan and
      Vehari collections also exhibited moderate levels (9- to 16-fold) of resistance
      to buprofezin. Furthermore, toxicity of neonicotinoids against immature stages
      was equal to that of insect growth regulators. The data also suggested that
      resistance in the field populations was stable. After selection for four
      generations with bifenthrin (G1 to G4), resistance to bifenthrin increased to 14
      fold compared with the laboratory susceptible population. Selection also
      increased resistance to fenpropathrin, lambdacyhalothrin, imidacloprid,
      acetamiprid, and diafenthuron. Cross-resistance and stability of resistance in
      the field populations is of some concern. Rotation of insecticides having no
      cross-resistance and targeting the control against immature stages may control
      the resistant insects, simultaneously reducing the selection pressure imposed.

PMID- 23865208
TI  - Monitoring changes in Bemisia tabaci (Hemiptera: Aleyrodidae) susceptibility to
      neonicotinoid insecticides in Arizona and California.
AB  - Bemisia tabaci (Gennadius) biotype B is a highly prolific and polyphagous
      whitefly that established in much of North America during the 1980s.
      Neonicotinoid insecticides have been fundamental in regaining control over
      outbreak populations of B. tabaci, but resistance threatens their sustainability.
      Susceptibility of B. tabaci in the southwestern United States to four
      neonicotinoid insecticides varied considerably across populations within each
      year over a 3 yr period. Using a variability ratio of highest LC50 to lowest LC50
      in field-collected whitefly adults from Arizona and California, the ranges of
      LC50(s) across all tests within compounds were highest to imidacloprid and lowest
      to thiamethoxam. Patterns of susceptibility were similar among all four
      neonicotinoid insecticides, but the greater variability in responses to
      imidacloprid and significantly higher LC50(s) attained indicated higher
      resistance levels to imidacloprid in all field populations. Further evidence of
      differential toxicities of neonicotinoids was observed in multiple tests of
      dinotefuran against imidacloprid-resistant lab strains that yielded significant
      differences in the LC50(s) of dinotefuran and imidacloprid in simultaneous
      bioassays. To test the possibility that resistance expression in field-collected
      insects was sometimes masked by stressful conditions, field strains cultured in a
      greenhouse without insecticide exposure produced significantly higher LC50(s) to
      all neonicotinoids compared with LC50(s) attained directly from the field. In
      harsh climates such as the American southwest, resistance expression in field
      collected test insects may be strongly influenced by environmental stresses such
      as high temperatures, overcrowding, and declining host plant quality.

PMID- 23865210
TI  - Baseline toxicity of metaflumizone and lack of cross resistance between
      indoxacarb and metaflumizone in diamondback moth (Lepidoptera: Plutellidae).
AB  - Diamondback moth, Plutella xylostella (L.) is a serious insect pest of vegetables
      worldwide, and has evolved resistance to various kinds of insecticides. Studies
      were conducted to determine the baseline toxicity of metaflumizone and the
      possibility of cross-resistance between metaflumizone and indoxacarb, two sodium
      channel blocking insecticides (SCBIs), in field populations of P. xylostella from
      China. The variation in susceptibility to metaflumizone among 29 field
      populations of P. xylostella collected from 14 geographical locations in China
      was less than five-fold, with 50% lethal concentrations (LC50(s)) varying from
      1.34 to 6.55 mg/liter. Limited variations in LC50(s) (less than five-fold,
      ranging from 1.76 to 8.16 mg/liter) were also observed in the four laboratory
      selected strains with high levels of resistance to abamectin, spinosad, fipronil,
      or Bt toxin Cry1Ac. The toxicity of metaflumizone and indoxacarb was compared
      among 23 out of the 29 field populations. When compared with the susceptible Roth
      strain, the JN-09B population showed the highest level of resistance to
      indoxacarb (110-fold), but two-fold tolerance to metaflumizone. The other 22
      populations (with 5- to 58-fold of resistance to indoxacarb) had 1- to three-fold
      tolerance to metaflumizone. Metaflumizone could provide an effective alternative
      insecticide for diamondback moth management. Although the field populations of P.
      xylostella tested with various levels of resistance to indoxacarb did not have
      cross-resistance to metaflumizone, metaflumizone should be rotated with other
      chemicals of different modes of action instead of indoxacarb.

PMID- 23865211
TI  - Cotton aphid (Heteroptera: Aphididae) susceptibility to commercial and
      experimental insecticides in the southern United States.
AB  - Cotton aphid, Aphis gossypii Glover, has a history of developing resistance to
      novel insecticides. A program is needed to monitor cotton aphid susceptibility to
      new insecticides. Concentration-mortality bioassays were conducted from 2008 to
      2011 to monitor the susceptibility of cotton aphids from fields across the
      midsouthern United States to thiamethoxam and sulfoxaflor. Flonicamid was
      included in 2010 and 2011. Bioassays followed the procedures described by the
      Insecticide Resistance Action Committee for testing neonicotinoids against cotton
      aphid. Mortality was rated at 48 and 72 h. These bioassays suggest that high
      levels of resistance to thiamethoxam occur in cotton aphid throughout the
      midsouthern United States. Resistance ratios ranged from 0.9 to 562.6 at 48 h,
      and from 0.9 to 29.1 at 72 h. Aphid colonies tested were considered susceptible
      to flonicamid and sulfoxaflor. The LC50 values ranged from 1.43 to 6.60 ppm for
      flonicamid. The LC50 values for sulfoxaflor ranged from 1.01 to 5.85 ppm and 0.92
      4.13 ppm at 48 and 72 h, respectively. These values represent the baseline
      variability of the susceptibility of cotton aphid to flonicamid and sulfoxaflor.
      The moderate level of variability observed combined with the high level of
      efficacy at low rates and the high reproductive rate of cotton aphid suggests
      that an effective resistance management plan needs to be devised for these
      insecticides. Flonicamid and sulfoxaflor should provide effective control of
      cotton aphid in areas where thiamethoxam resistance occurs. However, these
      insecticides need to be incorporated into a rotation strategy to preserve their
      efficacy against cotton aphid.

PMID- 23865212
TI  - Methods for rapid and effective PCR-based detection of 'Candidatus Liberibacter
      solanacearum' from the insect vector Bactericera cockerelli: streamlining the DNA
      extraction/purification process.
AB  - This study provides a protocol for rapid DNA isolation from psyllid vectors
      (Bactericera cockerelli and Diaphorina citri) that can be used directly with DNA
      based methods for the detection of 'Candidatus (Ca.) Liberibacter solanacearum,'
      the bacterial causal agent of potato zebra chip disease and eventually for 'Ca.
      Liberibacter asiaticus' the causal agent of huanglongbing disease in citrus. The
      fast DNA extraction protocol was designed to work with conventional polymerase
      chain reaction (cPCR) DNA amplification as well as Loop mediated PCR DNA
      amplification. Direct cPCR of the psyllid 28S rDNA gene from samples prepared
      using the fast DNA extraction method was as reliable as from samples prepared
      using standard DNA purification (> 97% from live insects) as tested in B.
      cockerelli. However, samples prepared using the fast DNA extraction method had to
      be diluted 1:100 in sterile water for reliable amplification, presumably to
      dilute PCR inhibitors in the crude extract. Similarly, both cPCR and loop
      mediated PCR DNA amplification detected 'Ca. Liberibacter' in psyllids infected
      with either the zebra chip or huanglongbing pathogen equally well from diluted
      samples prepared using the fast DNA extraction method or from samples prepared
      using a DNA purification step. In addition to being reliable, the time required
      to complete the fast DNA extraction for 10 samples was on average approximately 5
      min and required no special reagents or laboratory equipment. Thus, the fast DNA
      extraction method shows strong promise as a rapid, reliable, and expedient method
      when coupled with PCR-based analyses for detection of 'Ca. Liberibacter'
      pathogens in psyllids.

PMID- 23865213
TI  - Selection of endogenous reference genes for gene expression analysis in the
      Mediterranean species of the Bemisia tabaci (Hemiptera: Aleyrodidae) complex.
AB  - Quantitative real-time reverse transcription polymerase chain reaction is widely
      used for gene expression analysis, and robust normalization against stably
      expressed endogenous reference genes (ERGs) is necessary to obtain accurate
      results. In this study, the stability of nine housekeeping genes of the
      sweetpotato whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae) Mediterranean were
      evaluated in various conditions by quantitative real-time reverse transcription
      polymerase chain reaction using geNorm and Normfinder programs. Both programs
      suggested alpha-tubulin/ubiquitin and 18S small subunit ribosomal RNA the most
      stable genes for bacterium- and insecticide-treated whiteflies, respectively. For
      developmental stages, organs, and the samples including salivary glands and the
      whole body, transcription initiation factor TFIID subunit was calculated as the
      most stably expressed gene by both programs. In addition, we compared the RNA-seq
      data with the results of geNorm and Normfinder and found that the stable genes
      revealed by RNA-seq analysis were also the ERGs recommended by geNorm and
      Normfinder. Furthermore, the use of the most stable gene suggested by RNA-seq
      analysis as an ERG produced similar gene expression patterns compared with
      results generated from the normalization against the most stable gene selected by
      geNorm and Normfinder and multiple genes recommended by geNorm. It indicates that
      RNA-seq data are reliable and provide a great source for ERG candidate
      exploration. Our results benefit future research on gene expression profiles of
      whiteflies and possibly other organisms.

PMID- 23865214
TI  - Insect resistance in traditional and heirloom sweetpotato varieties.
AB  - Fifty-nine sweetpotato cultivars, including 16 heirlooms, 11 near-heirlooms
      (developed in the 1960s and 1970s), 19 cultivars from the 1980s, and 13 modern
      varieties (since 1990), were evaluated for resistance to soil insects in field
      experiments during 2010-2011 at the U.S. Department of Agriculture-Agriculture
      Research Service, U.S. Vegetable Laboratory (USDA-ARS, USVL), Charleston, SC.
      These experiments included two insect-susceptible control cultivars ('Beauregard'
      and 'SC1149-19') and four insect-resistant control cultivars ('Charleston
      Scarlet,''Regal,' 'Ruddy,' and 'Sumor') that were developed by the USDA-ARS, USVL
      sweetpotato breeding program. Sweetpotato genotypes differed significantly in
      resistance measured by the overall percentage of injured roots, WDS (Wireworm,
      Diabrotica, and Systena) index, the percentage of roots damaged by the
      sweetpotato weevil (Cylas formicarius F.), the percentage of roots damaged by the
      sweetpotato flea beetle (Chaetonema confinis Crotch), and the percentage of roots
      damaged by white grub larvae (including Plectris aliena Chapin and Phyllophaga
      spp.). Twenty-three sweetpotato cultivars had a lower percentage of injured roots
      than the susceptible control genotype, SC1149-19, while 14 varieties had a lower
      percentage of injured roots than Beauregard, one of the leading commercial orange
      fleshed cultivars in the United States. Over the 2-yr period, Ruddy (7.6%) had
      the lowest percentage of injured roots and 'Carolina Ruby' (84.6%) the highest
      percentage of injured roots. Carolina Ruby (1.07) also had the highest WDS index,
      but 15 genotypes had a significantly lower WDS index than either susceptible
      control, SC1149-19 (1.03) or Beauregard (0.82). Ruddy (0.07) and 'Murasaki-29'
      (0.09) had the lowest WDS indices. Forty-five genotypes had a significantly lower
      percentage infestation by flea beetles than SC1149-19 (12.3%), and the highest
      level of flea beetle infestation was for 'Bonita' (18.9%). The highest percent
      white grub infestation was for 'Caromex' (19.6%), however none of the genotypes
      had significantly less white grubs than the susceptible controls. The highest
      infestation of sweetpotato weevils was observed for SC1149-19 (17.9%), while 29
      genotypes had significantly lower percentage of sweetpotato weevil infestation
      than SC1149-19. The moderate to high levels of resistance to soil insect pests
      exhibited by many of these traditional and heirloom cultivars may provide useful
      sources of germplasm for sweetpotato breeding programs.

PMID- 23865215
TI  - Host plant resistance of cool-season (C3) turfgrasses to above- and belowground
      feeding by Tipula paludosa (Diptera: Tipulidae).
AB  - Feeding on above- and belowground plant tissues by Tipula paludosa Meigen during
      the period of rapid growth from second to forth instars is highly damaging to
      cool-season (C3) turfgrasses. It may be possible to reduce this damage by
      identifying grass genotypes that increase host plant protection. This study
      examined the impacts of plant genotype, endophyte infection, and plant ontogeny
      on host plant and insect responses during whole-plant feeding by T. paludosa. A
      series of no-choice greenhouse trials were conducted with third instar crane
      flies to determine 1) host plant tolerance in terms of reductions to above- and
      belowground plant biomass, 2) antixenosis resistance impacting insect behavior
      (emigration), and 3) antibiosis resistance impacting insect growth. Results
      showed that insect infestation level was the primary factor influencing plant
      biomass reductions. Belowground tissues were more tolerant to feeding than were
      aboveground tissues, with tall fescues, Festuca arundinacea Schreber, being most
      resistant to aboveground biomass reduction. Host plant associations with
      intercellular fungal endophytes (E+) decreased insect weight gain and decreased
      insect movement, but did not increase host plant tolerance. Plant ontogeny
      affected this response with insect weight gain significantly decreased on young
      (28 d) growth E+ grasses but not on old (90 d) growth E+ grasses, however. Host
      plant genotype and plant ontogeny can have significant impacts to host plant
      tolerance and insect physiology for T. paludosa larva. Furthermore, plant
      endophyte associations have apparent sublethal effects that impact insect fitness
      and may further enhance host plant protection.

PMID- 23865216
TI  - Response of wheat germplasm to infestation of English grain aphid (Hemiptera:
      Aphididae).
AB  - The English grain aphid, Sitobion avenae (F.), is a destructive insect pest of
      wheat. In this study, wheat germplasm was evaluated for resistance and tolerance
      to English grain aphid infestation. Except for spikelet number/spike, the 1,000
      kernel weight, spike weight, grain weight/ spike, and sterile spikelet
      number/spike of infested plants were all significantly impacted by English grain
      aphid infestation. Of 292 wheat accessions, only one genotype showed English
      grain aphid high resistance, and most genotypes showed intermediate resistance.
      Tolerance index values ranged widely among all accessions, but 11 genotypes had
      high tolerance to English grain aphid. Different resistance and tolerance
      parameters were positively correlated. Five green bug-resistant genotypes had a
      better English grain aphid tolerance index than other genotypes. Eleven genotypes
      exhibited a high or moderate level of tolerance and moderate level of resistance
      to English grain aphid. The broad-sense heritability of 1,000-kernel weight loss
      rate and peak aphid density were also estimated. English grain aphid resistant
      and tolerant lines identified in our study will be helpful in future breeding
      programs.

PMID- 23865217
TI  - Identification of novel sources of host plant resistance to known soybean aphid
      biotypes.
AB  - While soybean cultivars with resistance to the soybean aphid (Aphis glycines
      Matsumura) have been commercially released, the presence of virulent biotypes
      capable of overcoming plant resistance threatens the durability of host plant
      resistance as a stable management tactic. Novel sources of host plant resistance
      are needed to combat rapid biotype evolution. In this study, we screened 1,061
      soybean plant introductions (PIs) for resistance to three known biotypes of A.
      glycines. Based on a series of growth chamber and field screenings, we identified
      11 PIs that showed resistance to biotype 1 of A. glycines. Among these 11 PIs, 7
      PIs were resistant to biotype 2 and 5 PIs were resistant to biotype 3. Further,
      two PIs (PI 606390A from Vietnam and PI 340034 from South Korea) showed
      resistance to all three biotypes of A. glycines. We also identified 11 PIs that
      were potentially tolerant to A. glycines, illustrated by no adverse impact on
      plant quality because of A. glycines infestation. As resistant PIs identified in
      this study belong to maturity group II-IV, they can be readily crossed to early
      maturing cultivars adapted to north-central states of the United States, where A.
      glycines is a major pest. The genetic characterization of resistance in these PIs
      and incorporation of novel resistant genes into elite soybean cultivars will
      broaden the defense against multiple biotypes of A. glycines.

PMID- 23865218
TI  - Seasonal phenology, spatial distribution, and sampling plan for the invasive
      mealybug Phenacoccus peruvianus (Hemiptera: Pseudococcidae).
AB  - Phlenacoccus peruvianus Granara de Willink (Hemiptera: Pseudococcidae) is an
      invasive mealybug of Neotropical origin. In recent years it has invaded the
      Mediterranean Basin causing significant damages in bougainvillea and other
      ornamental plants. This article examines its phenology, location on the plant and
      spatial distribution, and presents a sampling plan to determine P. peruvianus
      population density for the management of this mealybug in southern Europe. Six
      urban green spaces with bougainvillea plants were periodically surveyed between
      March 2008 and September 2010 in eastern Spain, sampling bracts, leaves, and
      twigs. Our results show that P. peruvianus abundance was high in spring and
      summer, declining to almost undetectable levels in autumn and winter. The
      mealybugs showed a preference for settling on bracts and there were no
      significant migrations between plant organs. P. peruvianus showed a highly
      aggregated distribution on bracts, leaves, and twigs. We recommend abinomial
      sampling of 200 leaves and an action threshold of 55% infested leaves for
      integrated pest management purposes on urban landscapes and enumerative sampling
      for ornamental nursery management and additional biological studies.

PMID- 23865219
TI  - Use of black light traps to monitor the abundance, spread, and flight behavior of
      Halyomorpha halys (Hemiptera: Pentatomidae).
AB  - Monitoring the distribution and abundance of an invasive species is challenging,
      especially during the initial years of spread when population densities are low
      and basic biology and monitoring methods are being investigated. Brown marmorated
      stink bug (Halyomorpha halys (Stal)) is an invasive agricultural and urban pest
      that was first detected in the United States in the late 1990s. At the time of
      its detection, no method was available to effectively track H. halys populations,
      which are highly mobile and polyphagous. One possible solution was the
      utilization of black light traps, which are nonspecific traps attractive to night
      flying insects. To determine if black light traps are a reliable monitoring tool
      for H. halys, a state-wide network of 40-75 traps located on New Jersey farms
      were monitored from 2004 to 2011 for H. halys. This proved to be a highly
      effective method of monitoring H. halys populations and their spread at the
      landscape level. The total number of brown marmorated stink bug caught in New
      Jersey increased exponentially during this period at a rate of 75% per year.
      Logistic regression estimates that 2.84 new farms are invaded each year by H.
      halys. The results indicate that black light traps are attractive to early season
      populations as well as at low population densities. Weekly trap catch data are
      being used to generate state-wide population distribution maps made available to
      farmers in weekly newsletters and online. While no economic threshold currently
      exists for brown marmorated stink bug, the maps provide farmers with a tool to
      forecast pest pressure and plan management.

PMID- 23865220
TI  - Economic feasibility of methoprene applied as a surface treatment and as an
      aerosol alone and in combination with two other insecticides.
AB  - Economic evaluations of integrated pest management strategies are becoming
      increasingly important as restrictions on conventional insecticides continue to
      become more stringent and chemical control costs rise. Aerosol treatments with
      insect growth regulators alone and in combination with conventional contact
      insecticides may be a feasible alternative to expensive and highly toxic
      fumigants such as methyl bromide for control of the Indianmeal moth (Plodia
      interpunctella (Hubner)). Average calculated mortality of Indianmeal moth eggs
      exposed to surface applied methoprene, aerosol methoprene alone and in
      combination with esfenvalerate and synergized pyrethrins is 55.0, 69.0, and
      94.6%, respectively. Temperature effects on development time makes frequency and
      timing of insecticide applications very important as evidenced by simulations of
      population levels in response to a variety of treatment dates by diet, and become
      critical in situations where survival of Indianmeal moth is high. Using a
      measurement of risk that is equal to deviations below a target mortality goal
      (99%), we are able to optimize cost and frequency of application using simulated
      mortality data for each of the treatment strategies. Optimal timing of each
      insecticide treatment depends heavily on the rate of development by diet. This
      type of analysis helps pest control operators and managers by showing
      consequences of treatment scenarios in time and cost.

PMID- 23865221
TI  - Genetic identification of an unknown Rhagoletis fruit fly (Diptera: Tephritidae)
      infesting Chinese crabapple: implications for apple pest management.
AB  - The apple maggot, Rhagoletis pomonella (Walsh) (Diptera: Tephritidae), is a
      serious introduced quarantine pest in the apple (Malus spp.)-growing regions of
      central Washington and Oregon. In August 2011, seven fly larvae of unknown origin
      were discovered infesting fruit of an exotic Chinese crabapple, Malus spectabilis
      (Aiton) Borkhausen, in Kennewick, Benton County, WA. If confirmed, Chinese
      crabapple would have represented a new host for R. pomonella in Washington and
      triggered quarantine measures in a surrounding three-county region of the state.
      Here, we establish, based on five microsatellite loci, the identity of the
      crabapple-infesting larvae as the western cherry fruit fly, Rhagoletis
      indifferens Curran, representing a new host record for the fly. Morphological
      analysis of six flies reared to adulthood confirmed the genetic identification.
      The results demonstrate the utility of integrating rapid genetic identification
      methods with field surveys of economic pests, which decreased detection times by
      months, and avoided enacting costly quarantine measures that saved local and
      federal bodies > US$0.5 million in monitoring, inspection, and control costs. We
      discuss current ongoing efforts to develop rapid, accurate, and inexpensive on
      site DNA-based detection tools for R. pomonella that would have general
      applicability for the control of pest insects.

PMID- 23865222
TI  - Bayesian learning and predictability in a stochastic nonlinear dynamical model.
AB  - Bayesian inference methods are applied within a Bayesian hierarchical modeling
      framework to the problems of joint state and parameter estimation, and of state
      forecasting. We explore and demonstrate the ideas in the context of a simple
      nonlinear marine biogeochemical model. A novel approach is proposed to the
      formulation of the stochastic process model, in which ecophysiological properties
      of plankton communities are represented by autoregressive stochastic processes.
      This approach captures the effects of changes in plankton communities over time,
      and it allows the incorporation of literature metadata on individual species into
      prior distributions for process model parameters. The approach is applied to a
      case study at Ocean Station Papa, using particle Markov chain Monte Carlo
      computational techniques. The results suggest that, by drawing on objective prior
      information, it is possible to extract useful information about model state and a
      subset of parameters, and even to make useful long-term forecasts, based on
      sparse and noisy observations.

PMID- 23865223
TI  - A semiparametric Bayesian approach to estimating maximum reproductive rates at
      low population sizes.
AB  - The maximum annual reproductive rate (i.e., the slope at the origin in a stock
      recruitment relationship) is one of the most important biological reference
      points in fisheries; it sets the upper limit to sustainable fishing mortality.
      Estimating the maximum reproductive rate by fitting parametric models to stock
      recruitment data may not be a robust approach because two statistically
      indistinguishable models can generate radically different estimates. To mitigate
      this issue, we developed a flexible, semiparametric Bayesian approach based on a
      conditional Gaussian process prior specifically designed to estimate the maximum
      annual reproductive rate, and applied it to analyze simulated stock-recruitment
      data sets. Compared with results based on other Gaussian process priors, we found
      that the conditional Gaussian process prior provided superior results: the
      accuracy and precision of estimates were enhanced without increasing model
      complexity. Moreover, compared with parametric alternatives, performance of the
      conditional Gaussian process prior was comparable to that of the data-generating
      model and always better than the wrong model.

PMID- 23865224
TI  - Decision-making for ecosystem-based management: evaluating options for a krill
      fishery with an ecosystem dynamics model.
AB  - Decision-makers charged with implementing ecosystem-based management (EBM) rely
      on scientists to predict the consequences of decisions relating to multiple,
      potentially conflicting, objectives. Such predictions are inherently uncertain,
      and this can be a barrier to decision-making. The Convention on the Conservation
      of Antarctic Marine Living Resources requires managers of Southern Ocean
      fisheries to sustain the productivity of target stocks, the health and resilience
      of the ecosystem, and the performance of the fisheries themselves. The managers
      of the Antarctic krill fishery in the Scotia Sea and southern Drake Passage have
      requested advice on candidate management measures consisting of a regional catch
      limit and options for subdividing this among smaller areas. We developed a
      spatially resolved model that simulates krill-predator-fishery interactions and
      reproduces a plausible representation of past dynamics. We worked with experts
      and stakeholders to identify (1) key uncertainties affecting our ability to
      predict ecosystem state; (2) illustrative reference points that represent the
      management objectives; and (3) a clear and simple way of conveying our results to
      decision-makers. We developed four scenarios that bracket the key uncertainties
      and evaluated candidate management measures in each of these scenarios using
      multiple stochastic simulations. The model emphasizes uncertainty and simulates
      multiple ecosystem components relating to diverse objectives. We summarize the
      potentially complex results as estimates of the risk that each illustrative
      objective will not be achieved (i.e., of the state being outside the range
      specified by the reference point). This approach allows direct comparisons
      between objectives. It also demonstrates that a candid appraisal of uncertainty,
      in the form of risk estimates, can be an aid, rather than a barrier, to
      understanding and using ecosystem model predictions. Management measures that
      reduce coastal fishing, relative to oceanic fishing, apparently reduce risks to
      both the fishery and the ecosystem. However, alternative reference points could
      alter the perceived risks, so further stakeholder involvement is needed to
      identify risk metrics that appropriately represent their objectives.

PMID- 23865225
TI  - Evidence of market-driven size-selective fishing and the mediating effects of
      biological and institutional factors.
AB  - Market demand is often ignored or assumed to lead uniformly to the decline of
      resources. Yet little is known about how market demand influences natural
      resources in particular contexts, or the mediating effects of biological or
      institutional factors. Here, we investigate this problem by examining the Pacific
      red snapper (Lutjanus peru) fishery around La Paz, Mexico, where medium or "plate
      sized" fish are sold to restaurants at a premium price. If higher demand for
      plate-sized fish increases the relative abundance of the smallest (recruit size
      class) and largest (most fecund) fish, this may be a market mechanism to increase
      stocks and fishermen's revenues. We tested this hypothesis by estimating the
      effect of prices on the distribution of catch across size classes using daily
      records of prices and catch. We linked predictions from this economic choice
      model to a staged-based model of the fishery to estimate the effects on the stock
      and revenues from harvest. We found that the supply of plate-sized fish increased
      by 6%, while the supply of large fish decreased by 4% as a result of a 13% price
      premium for plate-sized fish. This market-driven size selection increased
      revenues (14%) but decreased total fish biomass (-3%). However, when market
      driven size selection was combined with limited institutional constraints, both
      fish biomass (28%) and fishermen's revenue (22%) increased. These results show
      that the direction and magnitude of the effects of market demand on biological
      populations and human behavior can depend on both biological attributes and
      institutional constraints. Fisheries management may capitalize on these
      conditional effects by implementing size-based regulations when economic and
      institutional incentives will enhance compliance, as in the case we describe
      here, or by creating compliance enhancing conditions for existing regulations.

PMID- 23865226
TI  - Biological ensemble modeling to evaluate potential futures of living marine
      resources.
AB  - Natural resource management requires approaches to understand and handle sources
      of uncertainty in future responses of complex systems to human activities. Here
      we present one such approach, the "biological ensemble modeling approach," using
      the Eastern Baltic cod (Gadus morhua callarias) as an example. The core of the
      approach is to expose an ensemble of models with different ecological assumptions
      to climate forcing, using multiple realizations of each climate scenario. We
      simulated the long-term response of cod to future fishing and climate change in
      seven ecological models ranging from single-species to food web models. These
      models were analyzed using the "biological ensemble modeling approach" by which
      we (1) identified a key ecological mechanism explaining the differences in
      simulated cod responses between models, (2) disentangled the uncertainty caused
      by differences in ecological model assumptions from the statistical uncertainty
      of future climate, and (3) identified results common for the whole model
      ensemble. Species interactions greatly influenced the simulated response of cod
      to fishing and climate, as well as the degree to which the statistical
      uncertainty of climate trajectories carried through to uncertainty of cod
      responses. Models ignoring the feedback from prey on cod showed large interannual
      fluctuations in cod dynamics and were more sensitive to the underlying
      uncertainty of climate forcing than models accounting for such stabilizing
      predator-prey feedbacks. Yet in all models, intense fishing prevented recovery,
      and climate change further decreased the cod population. Our study demonstrates
      how the biological ensemble modeling approach makes it possible to evaluate the
      relative importance of different sources of uncertainty in future species
      responses, as well as to seek scientific conclusions and sustainable management
      solutions robust to uncertainty of food web processes in the face of climate
      change.

PMID- 23865227
TI  - Identifying common pressure pathways from a complex network of human activities
      to support ecosystem-based management.
AB  - The marine environment is heavily exploited, but unintentional consequences cause
      wide-ranging negative effects to its characteristics. Linkage frameworks (e.g.,
      DPSIR [driver-pressure-state-impact-response]) are commonly used to describe an
      interaction between human activities and ecological characteristics of the
      ecosystem, but as each linkage is viewed independently, the diversity of
      pressures that affect those characteristics may not be identified or managed
      effectively. Here we demonstrate an approach for using linkages to build a simple
      network to capture the complex relationships arising from multiple sectors and
      their activities. Using data-analysis tools common to ecology, we show how
      linkages can be placed into mechanistically similar groups. Management measures
      can be combined into fewer and more simplified measures that target groups of
      pressures rather than individual pressures, which is likely to increase
      compliance and the success of the measure while reducing the cost of enforcement.
      Given that conservation objectives (regional priorities) can vary, we also
      demonstrate by way of a case study example from the Marine Strategy Framework
      Directive, how management priorities might change, and illustrate how the
      approach can be used to identify sectors for control that best support the
      conservation objectives.

PMID- 23865228
TI  - Sustainable exploitation and management of autogenic ecosystem engineers:
      application to oysters in Chesapeake Bay.
AB  - Autogenic ecosystem engineers are critically important parts of many marine and
      estuarine systems because of their substantial effect on ecosystem services.
      Oysters are of particular importance because of their capacity to modify coastal
      and estuarine habitats and the highly degraded status of their habitats
      worldwide. However, models to predict dynamics of ecosystem engineers have not
      previously included the effects of exploitation. We developed a linked population
      and habitat model for autogenic ecosystem engineers undergoing exploitation. We
      parameterized the model to represent eastern oyster (Crassostrea virginica) in
      upper Chesapeake Bay by selecting sets of parameter values that matched observed
      rates of change in abundance and habitat. We used the model to evaluate the
      effects of a range of management and restoration options including sustainability
      of historical fishing pressure, effectiveness of a newly enacted sanctuary
      program, and relative performance of two restoration approaches. In general,
      autogenic ecosystem engineers are expected to be substantially less resilient to
      fishing than an equivalent species that does not rely on itself for habitat.
      Historical fishing mortality rates in upper Chesapeake Bay for oysters were above
      the levels that would lead to extirpation. Reductions in fishing or closure of
      the fishery were projected to lead to long-term increases in abundance and
      habitat. For fisheries to become sustainable outside of sanctuaries, a
      substantial larval subsidy would be required from oysters within sanctuaries.
      Restoration efforts using high-relief reefs were predicted to allow recovery
      within a shorter period of time than low-relief reefs. Models such as ours, that
      allow for feedbacks between population and habitat dynamics, can be effective
      tools for guiding management and restoration of autogenic ecosystem engineers.

PMID- 23865229
TI  - Future species composition will affect forest water use after loss of eastern
      hemlock from southern Appalachian forests.
AB  - Infestation of eastern hemlock (Tsuga canadensis (L.) Carr.) with hemlock woolly
      adelgid (HWA, Adelges tsugae) has caused widespread mortality of this key canopy
      species throughout much of the southern Appalachian Mountains in the past decade.
      Because eastern hemlock is heavily concentrated in riparian habitats, maintains a
      dense canopy, and has an evergreen leaf habit, its loss is expected to have a
      major impact on forest processes, including transpiration (E(t)). Our goal was to
      estimate changes in stand-level E(t) since HWA infestation, and predict future
      effects of forest regeneration on forest E(t) in declining eastern hemlock stands
      where hemlock represented 50-60% of forest basal area. We used a combination of
      community surveys, sap flux measurements, and empirical models relating sap flux
      scaled leaf-level transpiration (E(L)) to climate to estimate the change in E(t)
      after hemlock mortality and forecast how forest E(t) will change in the future in
      response to eastern hemlock loss. From 2004 to 2011, eastern hemlock mortality
      reduced annual forest E(t) by 22% and reduced winter E(t) by 74%. As hemlock
      mortality increased, growth of deciduous tree species--especially sweet birch
      (Betula lenta L.), red maple (Acer rubrum L.), yellow poplar (Liriodendron
      tulipifera L.), and the evergreen understory shrub rosebay rhododendron
      (Rhododendron maximum L.)--also increased, and these species will probably
      dominate post-hemlock riparian forests. All of these species have higher daytime
      E(L) rates than hemlock, and replacement of hemlock with species that have less
      conservative transpiration rates will result in rapid recovery of annual stand
      E(t). Further, we predict that annual stand E(t) will eventually surpass E(t)
      levels observed before hemlock was infested with HWA. This long-term increase in
      forest E(t) may eventually reduce stream discharge, especially during the growing
      season. However, the dominance of deciduous species in the canopy will result in
      a permanent reduction in winter E(t) and possible increase in winter stream
      discharge. The effects of hemlock die-off and replacement with deciduous species
      will have a significant impact on the hydrologic flux of forest transpiration,
      especially in winter. These results highlight the impact that invasive species
      can have on landscape-level ecosystem fluxes.

PMID- 23865230
TI  - Hydrogeomorphology explains acidification-driven variation in aquatic biological
      communities in the Neversink Basin, USA.
AB  - Describing the distribution of aquatic habitats and the health of biological
      communities can be costly and time-consuming; therefore, simple, inexpensive
      methods to scale observations of aquatic biota to watersheds that lack data would
      be useful. In this study, we explored the potential of a simple "hydrogeomorphic"
      model to predict the effects of acid deposition on macroinvertebrate, fish, and
      diatom communities in 28 sub-watersheds of the 176-km2 Neversink River basin in
      the Catskill Mountains of New York State. The empirical model was originally
      developed to predict stream-water acid neutralizing capacity (ANC) using the
      watershed slope and drainage density. Because ANC is known to be strongly related
      to aquatic biological communities in the Neversink, we speculated that the model
      might correlate well with biotic indicators of ANC response. The hydrogeomorphic
      model was strongly correlated to several measures of macroinvertebrate and fish
      community richness and density, but less strongly correlated to diatom acid
      tolerance. The model was also strongly correlated to biological communities in 18
      sub-watersheds independent of the model development, with the linear correlation
      capturing the strongly acidic nature of small upland watersheds (< 1 km2).
      Overall, we demonstrated the applicability of geospatial data sets and a simple
      hydrogeomorphic model for estimating aquatic biological communities in areas with
      stream-water acidification, allowing estimates where no direct field observations
      are available. Similar modeling approaches have the potential to complement or
      refine expensive and time-consuming measurements of aquatic biota populations and
      to aid in regional assessments of aquatic health.

PMID- 23865231
TI  - Demographic effects on the use of genetic options for the control of
      mosquitofish, Gambusia holbrooki.
AB  - This study tests the sensitivity of genetically based pest control options based
      on sex ratio distortion to intra- and intersexual aggressive interactions that
      affect male and female survival and fitness. Data on these interactions and their
      impacts were gathered for the mosquitofish Gambusia holbrooki (Poeciliidae), a
      promiscuous species with a strongly male-biased operational sex ratio and well
      documented male harassment of females. The experimental design consisted of an
      orthogonal combination of two population densities and three sex ratios, ranging
      from strongly male-biased to strongly female-biased, and long-term observations
      of laboratory populations. Contrary to expectations, the number of males in a
      population had little evident effect on population demographics. Rather, the
      density of adult females determined population fecundity (as a result of a stock
      recruitment relationship involving females, but not males), constrained male
      densities (apparently as a result of cannibalism or intersexual aggression), and
      regulated itself (most likely through effects of intrasexual aggression on female
      recruitment). The principal effect of males was to constrain their own densities
      via effects of male-male aggression on adult male mortality rates. Through use of
      a realistically parameterized genetic/demographic model, we show that of three
      different genetic options applied to control G. holbrooki, one based on
      recombinant sex ratio distortion (release of Female Lethal carriers) is
      marginally more efficient than a sterile male release program, and both
      outperform an option based on chromosomal sex ratio distortion (Trojan W).
      Nonlinear dependence of reproductive rate on female density reduces the efficacy
      of all three approaches. The major effect of intra- and intersexual aggression is
      mediated through females, whose interactions reduce female numbers and increase
      the efficacy of a control program based on sex ratio. Socially mediated male
      mortality has a small impact on control programs due to operational sex ratios
      that are heavily male-biased. The sensitivity of sex ratio-based control options
      to social factors will depend on the mating system of the targeted pest, but
      evidence of widespread density-dependent population regulation suggests that, for
      most species, the effects of elevated adult mortality (due to intra- and
      intersexual aggression) on control programs are likely to be slight.

PMID- 23865232
TI  - Mechanistic models for the spatial spread of species under climate change.
AB  - Global climate change is a major threat to biodiversity. The most common methods
      for predicting the response of biodiversity to changing climate do not explicitly
      incorporate fundamental evolutionary and ecological processes that determine
      species responses to changing climate, such as reproduction, dispersal, and
      adaptation. We provide an overview of an emerging mechanistic spatial theory of
      species range shifts under climate change. This theoretical framework explicitly
      defines the ecological processes that contribute to species range shifts via
      biologically meaningful dispersal, reproductive, and climate envelope parameters.
      We present methods for estimating the parameters of the model with widely
      available species occurrence and abundance data and then apply these methods to
      empirical data for 12 North American butterfly species to illustrate the
      potential use of the theory for global change biology. The model predicts species
      persistence in light of current climate change and habitat loss. On average, we
      estimate that the climate envelopes of our study species are shifting north at a
      rate of 3.25 +/- 1.36 km/yr (mean +/- SD) and that our study species produce 3.46
      +/- 1.39 (mean +/- SD) viable offspring per individual per year. Based on our
      parameter estimates, we are able to predict the relative risk of our 12 study
      species for lagging behind changing climate. This theoretical framework improves
      predictions of global change outcomes by facilitating the development and testing
      of hypotheses, providing mechanistic predictions of current and future range
      dynamics, and encouraging the adaptive integration of theory and data. The theory
      is ripe for future developments such as the incorporation of biotic interactions
      and evolution of adaptations to novel climatic conditions, and it has the
      potential to be a catalyst for the development of more effective conservation
      strategies to mitigate losses of biodiversity from global climate change.

PMID- 23865233
TI  - Hedgerow restoration promotes pollinator populations and exports native bees to
      adjacent fields.
AB  - In intensive agricultural landscapes, restoration within farms could enhance
      biodiversity and ecosystem services such as pollination by native pollinators.
      Although governments and conservation groups are promoting small-scale
      restoration on working farms, there are few studies that assess whether these
      practices enhance pollinator communities in restored areas. Further, there is no
      information on whether floral enhancements will deplete pollinators in adjacent
      fields by concentrating ambient populations or whether they result in a net
      increase in abundance in adjacent farm fields. We investigated whether field
      edges restored with native perennial plants in California's Central Valley
      agricultural region increased floral abundance and potential bee nesting sites,
      and native bee and syrphid fly abundance and diversity, in comparison to
      relatively unmanaged edges. Native bees and syrphid flies collected from flowers
      were more abundant, species-rich, and diverse at hedgerow sites than in weedy,
      unmanaged edges. Abundance of bees collected passively in pan traps was
      negatively correlated with floral abundance, was significantly different from
      communities captured by net sampling from flowers, and did not distinguish
      between site types; we therefore focused on the results of net samples and visual
      observations. Uncommon species of native bees were sevenfold more abundant on
      hedgerow flowers than on flowers at weedy, unmanaged edges. Of the species on
      flowers at hedgerows, 40% were exclusive to hedgerow sites, but there were no
      species exclusively found on flowers at control sites. Hedgerows were especially
      important for supporting less-common species of native bees in our intensive
      agricultural landscape. Hedgerows did not concentrate ambient native bee, honey
      bee, or syphid fly populations, and they acted as net exporters of native bees
      into adjacent fields. Within-farm habitat restoration such as hedgerow creation
      may be essential for enhancing native pollinator abundance and diversity, and for
      pollination services to adjacent crops.

PMID- 23865234
TI  - Nonrandom extinction patterns can modulate pest control service decline.
AB  - Changes in biodiversity will mediate the consequences of agricultural
      intensification and expansion for ecosystem services. Regulating services, like
      pollination and pest control, generally decline with species loss. In nature,
      however, relationships between service provision and species richness are not
      always strong, partially because anthropogenic disturbances purge species from
      communities in nonrandom orders. The same traits that make for effective service
      providers may also confer resistance or sensitivity to anthropogenic
      disturbances, which may either temper or accelerate declines in service provision
      with species loss. We modeled a community of predators interacting with insect
      pest prey, and identified the contexts in which pest control provision was most
      sensitive to species loss. We found pest populations increased rapidly when
      functionally unique and dietary-generalist predators were lost first, with up to
      20% lower pest control provision than random loss. In general, pest abundance
      increased most in the scenarios that freed more pest species from predation.
      Species loss also decreased the likelihood that the most effective service
      providers were present. In communities composed of species with identical traits,
      predators were equally effective service providers and, when competing predators
      went extinct, remaining community members assumed their functional roles. In more
      realistic trait-diverse communities, predators differed in pest control efficacy,
      and remaining predators could not fully compensate for the loss of their
      competitors, causing steeper declines in pest control provision with predator
      species loss. These results highlight diet breadth in particular as a key
      predictor of service provision, as it affects both the way species respond to and
      alter their environments. More generally, our model provides testable hypotheses
      for predicting how nonrandom species loss alters relationships between
      biodiversity and pest control provision.

PMID- 23865235
TI  - Competition and facilitation between a native and a domestic herbivore: trade
      offs between forage quantity and quality.
AB  - Potential competition between native and domestic herbivores is a major
      consideration influencing the management and conservation of native herbivores in
      rangeland ecosystems. In grasslands of the North American Great Plains, black
      tailed prairie dogs (Cynomys ludovicianus) are widely viewed as competitors with
      cattle but are also important for biodiversity conservation due to their role in
      creating habitat for other native species. We examined spatiotemporal variation
      in prairie dog effects on growing-season forage quality and quantity using
      measurements from three colony complexes in Colorado and South Dakota and from a
      previous study of a fourth complex in Montana. At two complexes experiencing
      below-average precipitation, forage availability both on and off colonies was so
      low (12-54 g/m2) that daily forage intake rates of cattle were likely constrained
      by instantaneous intake rates and daily foraging time. Under these dry
      conditions, prairie dogs (1) substantially reduced forage availability, thus
      further limiting cattle daily intake rates, and (2) had either no or a small
      positive effect on forage digestibility. Under such conditions, prairie dogs are
      likely to compete with cattle in direct proportion to their abundance. For two
      complexes experiencing above-average precipitation, forage quantity on and off
      colonies (77-208 g/m2) was sufficient for daily forage intake of cattle to be
      limited by digestion rather than instantaneous forage intake. At one complex
      where prairie dogs enhanced forage digestibility and [N] while having no effect
      on forage quantity, prairie dogs are predicted to facilitate cattle mass gains
      regardless of prairie dog abundance. At the second complex where prairie dogs
      enhanced digestibility and [N] but reduced forage quantity, effects on cattle can
      vary from competition to facilitation depending on prairie dog abundance. Our
      findings show that the high spatiotemporal variation in vegetation dynamics
      characteristic of semiarid grasslands is paralleled by variability in the
      magnitude of competition between native and domestic grazers. Competitive
      interactions evident during dry periods may be partially or wholly offset by
      facilitation during periods when forage digestibility is enhanced and forage
      quantity does not limit the daily intake rate of cattle.

PMID- 23865236
TI  - The idiosyncrasies of place: geographic variation in the climate-distribution
      relationships of the American pika.
AB  - Although climate acts as a fundamental constraint on the distribution of
      organisms, understanding how this relationship between climate and distribution
      varies over a species' range is critical for addressing the potential impacts of
      accelerated climate change on biodiversity. Bioclimatic niche models provide
      compelling evidence that many species will experience range shifts under
      scenarios of global change, yet these broad, macroecological perspectives lack
      specificity at local scales, where unique combinations of environment, biota, and
      history conspire against generalizations. We explored how these idiosyncrasies of
      place affect the climate-distribution relationship of the American pika (Ochotona
      princeps) by replicating intensive field surveys across bioclimatic gradients in
      eight U.S. national parks. At macroecological scales, the importance of climate
      as a constraint on pika distribution appears unequivocal; forecasts suggest that
      the species' range will contract sharply in coming decades. However, the species
      persists outside of its modeled bioclimatic envelope in many locations, fueling
      uncertainty and debate over its conservation status. Using a Bayesian
      hierarchical approach, we modeled variation in local patterns of pika
      distribution along topographic position, vegetation cover, elevation,
      temperature, and precipitation gradients in each park landscape. We also
      accounted for annual turnover in site occupancy probabilities. Topographic
      position and vegetation cover influenced occurrence in all parks. After
      accounting for these factors, pika occurrence varied widely among parks along
      bioclimatic gradients. Precipitation by itself was not a particularly influential
      predictor. However, measures of heat stress appeared most influential in the
      driest parks, suggesting an interaction between the strength of climate effects
      and the position of parks along precipitation gradients. The combination of high
      elevation, cold temperatures, and high precipitation lowered occurrence
      probabilities in some parks, suggesting an upper elevational limit for pikas in
      some environments. Our results demonstrate that the idiosyncrasies of place
      influence both the nature and strength of the climate-distribution relationship
      for the American pika. Fine-grained, but geographically extensive, studies
      replicated across multiple landscapes offer insights important to assessing the
      impacts of climate change that otherwise may be masked at macroecological scales.
      The hierarchical approach to modeling provides a coherent conceptual and
      technical framework for gaining these insights.

PMID- 23865237
TI  - Patch size and edge proximity are useful predictors of brood parasitism but not
      nest survival of grassland birds.
AB  - Declines of migratory birds have led to increased focus on causative factors for
      these declines, including the potential adverse effects of habitat fragmentation
      on reproductive success. Although numerous studies have addressed how proximity
      to a habitat edge, patch size, or landscape context influence nest survival or
      brood parasitism, many have failed to find the purported effects. Furthermore,
      many have sought to generalize patterns across large geographic areas and
      habitats. Here, we examined evidence for effects of edge proximity, patch size,
      and landscape context on nest survival and brood parasitism of grassland birds, a
      group of conservation concern. The only consistent effect was a positive
      association between edge proximity and brood parasitism. We examined effects of
      patch size on nest survival (37 studies) and brood parasitism (30 studies)
      representing 170 and 97 different estimates, respectively, with a total sample
      size of > 14000 nests spanning eastern North America. Nest survival weakly
      increased with patch size in the Great Plains, but not in the Midwestern or
      Eastern United States, and brood parasitism was inversely related to patch size
      and consistently greater in the Great Plains. The consistency in brood parasitism
      relative to nest survival patterns is likely due to parasitism being caused by
      one species, while nest survival is driven by a diverse and variable suite of
      nest predators. Often, studies assume that predators responsible for nest
      predation, the main driver of nest success, either are the same or exhibit the
      same behaviors across large geographic areas. These results suggest that a better
      mechanistic understanding of nest predation is needed to provide meaningful
      conservation recommendations for improving grassland bird productivity, and that
      the use of general recommendations across large geographic areas should only be
      undertaken when sufficient data are available from all regions.

PMID- 23865238
TI  - Exploring the ecological processes driving geographical patterns of breeding bird
      richness in British Columbia, Canada.
AB  - British Columbia (BC), Canada, has a diverse landscape that provides breeding
      habitat for > 300 avian species, and the recent development of the BC Breeding
      Bird Atlas data set presents key information for exploring the landscape
      conditions which lead to biological richness. We used the volunteer-collected raw
      breeding bird evidence data set to analyze the effects of sampling biases on
      spatial distribution of observed breeding bird species and implemented regression
      tree analysis (Random Forests) to examine the influence of productivity, ambient
      energy, and habitat heterogeneity on independently measured breeding bird
      richness. Results indicated that total breeding species richness is correlated
      with total survey effort (alpha < 0.001). By stratifying species richness by
      survey effort, we observed that ambient energy is the top-ranked environmental
      predictor of breeding bird richness across BC, which, when used in combination
      with a number of other environmental variables, explains -40% of the variation in
      richness. Using our modeled relationships, we predicted breeding bird species
      richness in the areas of BC not presently surveyed between three and six hours.
      The majority of the productive Boreal Plains, the southern portion of the Taiga
      Plains region, the lowlands of the Southern and Central Interior, along the Rocky
      Mountain Trench, and the coastal areas of the Georgia Depression are predicted to
      have the highest categories of breeding richness (35-57 unique species). Our
      results support ongoing species diversity gradient research, which identifies
      ambient energy as an important factor influencing species diversity distributions
      in the Northern Hemisphere. By linking breeding bird richness to environmental
      data derived from remotely sensed data and systematically collected climate data,
      we demonstrate the potential to monitor shifts in ambient energy as a surrogate
      for vertebrate habitat condition affecting population levels. By analyzing the
      influence of survey effort on species richness metrics, we also highlight the
      need to consider adding attributes to the raw breeding bird data set to describe
      observer experience, such as hours or seasons spent surveying, and provide survey
      dates to allow greater flexibility for removing survey bias. These additions can
      increase the utility of atlas data for species richness studies useful for
      conservation planning.

PMID- 23865239
TI  - Fire regime zonation under current and future climate over eastern Canada.
AB  - Fire is a major disturbance in Canadian forests. Along with fuel and ignition
      characteristics, climatic conditions are seen as one of the main drivers of fire
      regimes. Projected changes in climate are expected to significantly influence
      fire regimes in Canada. As fire regime greatly shapes large-scale patterns in
      biodiversity, carbon, and vegetation, as well as forest and fire management
      strategies, it becomes necessary to define regions where current and future fire
      regimes are homogeneous. Random Forests (RF) modeling was used to relate fire
      regime attributes prevailing between 1961 and 1990 in eastern Canada with
      climatic/fire-weather and environmental variables. Using climatic normals outputs
      from the Canadian Regional Climate Model (CRCM), we delineated current (1961
      1990) and future (2011-2040, 2040-2070, 2071 2100) homogeneous fire regime (HFR)
      zones. Heterogeneous response of fire regime to climate changes is projected for
      eastern Canada with some areas (e.g., western Quebec) experiencing very small
      alterations while others (e.g., southeastern Ontario) are facing great shifts.
      Overall, models predicted a 2.2- and 2.4-fold increase in the number of fires and
      the annual area burned respectively mostly as a result of an increase in extreme
      fire-weather normals and mean drought code. As extreme fire danger would occur
      later in the fire season on average, the fire season would shift slightly later
      (5-20 days) in the summer for much of the study area while remaining relatively
      stable elsewhere. Although fire regime values would change significantly over
      time, most zone boundaries would remain relatively stable. The information
      resulting from HFR zonations is clearly of interest for forest and fire
      management agencies as it reveals zones with peculiar fire regimes that would
      have been hidden otherwise using predefined administrative or ecological
      stratifications.

PMID- 23865240
TI  - Estimating fire interval bounds using vital attributes: implications of
      uncertainty and among-population variability.
AB  - Identifying the range of appropriate fire return intervals is crucial for
      ecosystem management in fire-prone environments. Plant vital attributes and
      changes in their associated trait values with time since fire are important
      indicators of suitable fire interval bounds to conserve biodiversity. However,
      using vital attributes to derive prescriptions for acceptable fire intervals
      remains challenging due to (1) uncertainty regarding how traits are best
      measured, (2) uncertainty in the acceptable ranges of trait values to avoid local
      extinctions, and (3) potential for variability among populations in the time
      taken postfire to reach trait threshold values. Using a time-since-fire gradient
      in contrasting mallee and mallee-heath vegetation types of southwestern
      Australia, we calculate, compare, and aggregate fire interval bound predictions
      from nine serotinous non-resprouters and seven serotinous resprouters across
      these three sources of uncertainty or variation. Relationships between time since
      fire and both trait measures reflecting minimum fire interval (mean number of
      closed fruit per plant or proportion of plants with closed fruit) were typically
      significant, had reasonable goodness of fit, and showed similar patterns of
      change with time since fire. Significant relationships reflecting maximum fire
      interval were less frequent but were more commonly detected using direct measures
      of mortality than using evidence for decline in reproductive potential. Of the
      two sources of uncertainty, trait value threshold selection caused more
      substantial differences in estimated interval bounds than trait measurement
      method. Variation between populations increased with greater estimated minimum
      interval length and, in some species, rendered interval estimates of limited
      practical value. On balance, we conclude that measures of vital attribute traits
      offer a transparent approach for estimating fire interval bounds at the plant
      community level, but selection of trait value thresholds is in need of stronger
      biological justification in their application. Further, variation between
      populations should be explicitly sampled if fire interval estimates are to be
      applied across the landscape.

PMID- 23865241
TI  - Quantifying the sampling error in tree census measurements by volunteers and its
      effect on carbon stock estimates.
AB  - A typical way to quantify aboveground carbon in forests is to measure tree
      diameters and use species-specific allometric equations to estimate biomass and
      carbon stocks. Using "citizen scientists" to collect data that are usually time
      consuming and labor-intensive can play a valuable role in ecological research.
      However, data validation, such as establishing the sampling error in volunteer
      measurements, is a crucial, but little studied, part of utilizing citizen science
      data. The aims of this study were to (1) evaluate the quality of tree diameter
      and height measurements carried out by volunteers compared to expert scientists
      and (2) estimate how sensitive carbon stock estimates are to these measurement
      sampling errors. Using all diameter data measured with a diameter tape, the
      volunteer mean sampling error (difference between repeated measurements of the
      same stem) was 9.9 mm, and the expert sampling error was 1.8 mm. Excluding those
      sampling errors > 1 cm, the mean sampling errors were 2.3 mm (volunteers) and 1.4
      mm (experts) (this excluded 14% [volunteer] and 3% [expert] of the data). The
      sampling error in diameter measurements had a small effect on the biomass
      estimates of the plots: a volunteer (expert) diameter sampling error of 2.3 mm
      (1.4 mm) translated into 1.7% (0.9%) change in the biomass estimates calculated
      from species-specific allometric equations based upon diameter. Height sampling
      error had a dependent relationship with tree height. Including height
      measurements in biomass calculations compounded the sampling error markedly; the
      impact of volunteer sampling error on biomass estimates was +/- 15%, and the
      expert range was +/- 9%. Using dendrometer bands, used to measure growth rates,
      we calculated that the volunteer (vs. expert) sampling error was 0.6 mm (vs. 0.3
      mm), which is equivalent to a difference in carbon storage of +/- 0.011 kg C/yr
      (vs. +/- 0.002 kg C/yr) per stem. Using a citizen science model for monitoring
      carbon stocks not only has benefits in educating and engaging the public in
      science, but as demonstrated here, can also provide accurate estimates of biomass
      or forest carbon stocks.

PMID- 23865242
TI  - Predicting yields of short-rotation hybrid poplar (Populus spp.) for the United
      States through model-data synthesis.
AB  - Hybrid poplar (Populus spp.) is an important biomass crop being evaluated for
      cellulosic ethanol production. Predictions of poplar growth, rotation period, and
      soil carbon sequestration under various growing conditions, soils, and climates
      are critical for farmers and managers planning to establish short-rotation
      forestry (SRF) plantations. In this study, we used an ecoinformatics workflow,
      the Predictive Ecosystem Analyzer (PEcAn), to integrate literature data and field
      measurements into the Ecosystem Demography 2 (ED2) model to estimate yield
      potential of poplar plantations. Within PEcAn 164 records of seven different
      traits from the literature were assimilated using a Bayesian meta-analysis. Next,
      variance decomposition identified seven variables for further constraint that
      contributed > 80% to the uncertainty in modeled yields: growth respiration, dark
      respiration, quantum efficiency, mortality coefficient, water conductance, fine
      root allocation, and root turnover rate. Assimilation of observed yields further
      constrained uncertainty in model parameters (especially dark respiration and root
      turnover rate) and biomass estimates. Additional measurements of growth
      respiration, mortality, water conductance, and quantum efficiency would provide
      the most efficient path toward further constraint of modeled yields. Modeled
      validation demonstrated that ED2 successfully captured the interannual and
      spatial variability of poplar yield observed at nine independent sites. Site
      level analyses were conducted to estimate the effect of land use change to SRF
      poplar on soil C sequestration compared to alternate land uses. These suggest
      that poplar plantations became a C sink within 18 years of conversion from corn
      production or existing forest. Finally, poplar yields were estimated for the
      contiguous United States at a half degree resolution in order to determine
      potential productivity, estimate the optimal rotation period, and compare poplar
      to perennial grass yields. This regional projection suggests that poplar yield
      varies considerably with differences in soil and climate, reaching as much as 18
      Mg x ha(-1) x yr(-1) in eastern, southern, and northwest regions. In New England,
      the upper Midwest, and northern California, yields are predicted to exceed those
      of the highly productive C4 perennial grass, Miscanthus. In these poplar
      productive regions, 4-11 year rotations give the highest potential yields. In
      conclusion, poplar plantations are predicted to have a high yield potential
      across a wide range of climates and soils and could be sustainable in soil C
      sequestration.

PMID- 23865243
TI  - [Preserving our civil and professional indignation].

PMID- 23865244
TI  - [Results of a new consensus development conference for improving the management
      of bedsores].

PMID- 23865245
TI  - [A new treatment for venous leg ulcers].

PMID- 23865246
TI  - [Multi-drug resistant bacteria, a complex mechanism].
AB  - Bacteria are said to be multidrug resistant when they are only sensitive to a
      small number of antibiotics used as treatments. This problem of resistance
      appeared in hospitals soon after antibiotics were first used. In the 1960s,
      strains of staphylococcus became resistant to penicillin.

PMID- 23865247
TI  - [Multi-drug resistant bacteria and antibiotics].
AB  - Antibiotics are still routinely prescribed, despite the increase in bacterial
      resistance to these drugs. To contain this public health problem, doctors need to
      be better trained and the general public better informed.

PMID- 23865248
TI  - [Managing multi-drug resistant bacteria in nursing homes].
AB  - The application of standard and sometimes additional hygiene precautions also
      concerns nursing homes, in order to prevent the transmission of multi-drug
      resistant bacteria. If a resident is a carrier or infected by a multi-drug
      resistant bacteria, the care must be organised accordingly but geographic
      confinement is rarely adapted.

PMID- 23865249
TI  - [Multi-drug resistant bacteria in the home].
AB  - Short hospital stays, outpatient care, home care, the treatment of patients is
      evolving and the role of home nursing care professionals is essential. This
      article reviews the procedures to respect to improve the quality of care provided
      in the patient's home.

PMID- 23865250
TI  - [Harassment in the public sector].
AB  - The French Labour Code, which provides full protection against moral and sexual
      harassment, is not applicable to public sector workers. The public hospital is
      however not exempt from such behaviour, which could go unpunished. Public sector
      workers are therefore protected by the French General Civil Service Regulations
      and the penal code.

PMID- 23865251
TI  - [Benevolence at the heart of care].
AB  - The procedures to assess practices in health or medical social institutions aim
      to improve the quality and safety of health care. The respect of good practices
      concerns all players in the health care system. At practice level, the risk of
      maltreatment, a major potential hindrance to the quality of care, must always be
      borne in mind.

PMID- 23865252
TI  - [The social dimension of care favors care in the home].
AB  - Caring for sick people who are losing their autonomy in their home requires a
      range of social actions, in terms of the search for human, material as well as
      financial resources. Home care nurses play a specific role in this social aspect
      of care which, if it is planned for, significantly contributes to avoiding
      hospitalisations.

PMID- 23865253
TI  - [Nursing care of the patient in a confusional state].

PMID- 23865254
TI  - [Kidney transplantation and diet].

PMID- 23865255
TI  - [Medication administration and dose calculation].

PMID- 23865256
TI  - [The placement and removal of nasogastric intubation].

PMID- 23865257
TI  - [Demand scientific evidence for surrogate motherhood].

PMID- 23865258
TI  - [Risks for the children in surrogacy. Important to follow the outcome of in vitro
      fertilization].

PMID- 23865259
TI  - [DSM-IV has become DSM-5. Psychiatric diagnostics has taken a step forward].

PMID- 23865260
TI  - [The proportion of laparoscopic colorectal cancer surgery should increase. Sweden
      is left behind--large regional differences within the country].

PMID- 23865261
TI  - [Prescription of warfarin after stroke care showed weaknesses. Procedures for
      documentation and indications should be improved, according to Malmo study].

PMID- 23865262
TI  - [Modern imaging important tool in diagnosing spondyloarthritis].

PMID- 23865263
TI  - [Swedish forensic psychiatry changing. Comprehensive proposal for legislative
      changes in the Psychiatry Law Inquiry report].

PMID- 23865264
TI  - [Contradictory whether paracetamol is contraindicated after childhood
      vaccination].

PMID- 23865265
TI  - [Respect for fellow human beings own choice].

PMID- 23865266
TI  - [Screening for abdominal aortic aneurysm is an effective and evidence-based
      medical intervention].

PMID- 23865267
TI  - [Wilderness Medicine requires improvisation and evidence-based knowledge].

PMID- 23865268
TI  - [Female physicians' salaries should not continue to lag behind].

PMID- 23865269
TI  - [The employer is responsible for lack of objectivity].

PMID- 23865270
TI  - [The Swedish Medical Association--it's not enough!].

PMID- 23865271
TI  - [We need to make others understand what is required].

PMID- 23865272
TI  - [Health Library online--an inexhaustible source of knowledge].

PMID- 23865274
TI  - Nursing owns nutrition!

PMID- 23865273
TI  - [It usually turns out well].

PMID- 23865275
TI  - When it's good to remember.

PMID- 23865276
TI  - Critical role of nutrition in improving quality of care: an interdisciplinary
      call to action to address adult hospital malnutrition.
AB  - The current era of health care delivery, with its focus on providing high
      quality, affordable care, presents many challenges to hospital-based health
      professionals. The prevention and treatment of hospital malnutrition offers a
      tremendous opportunity to optimize the overall quality of patient care, improve
      clinical outcomes, and reduce costs. Unfortunately, malnutrition continues to go
      unrecognized and untreated in many hospitalized patients. This article represents
      a call to action from the interdisciplinary Alliance to Advance Patient Nutrition
      to highlight the critical role of nutrition intervention in clinical care and
      suggest practical ways for prompt diagosis and treatment of malnourished patients
      and those at risk for malnutrition. We underscore the importance of an
      interdisciplinary approach to addressing malnutrition both in the hospital and in
      the acute post-hospital phase. It is well recognized that malnutrition is
      associated with adverse clinical outcomes. Although data vary across studies,
      available evidence shows early nutrition intervention can reduce complication
      rates, length of hospital stay, re-admission rates, mortality, and cost of care.
      The key is to identify patients systematically who are malnourished or at risk
      and to promptly intervene. We present a novel care model to drive improvement,
      emphasizing the following six principles: (1) create an institutional culture
      where all stakeholders value nutrition; (2) redefine clinicians' roles to include
      nutrition care; (3) recognize and diagnose all malnourished patients and those at
      risk; (4) rapidly implement comprehensive nutrition interventions and continued
      monitoring; (5) communicate nutrition care plans; and (6) develop a comprehensive
      discharge nutrition care and education plan.

PMID- 23865277
TI  - Medical home model of patient-centered health care.

PMID- 23865278
TI  - Understanding nurse-to-nurse relationships and their impact on work environments.
AB  - INTRODUCTION: Nurse-to-nurse relationships are a key component in determining the
      health of a work setting. Because of the impact that such relationships can have
      on patients, health care organizations, nurses, and the nursing profession, it is
      imperative to understand how nurses relate to each other. PURPOSE: The purpose of
      this article is to present findings from a study that explored how direct-care
      nurses relate to each other in everyday interactions on patient care units.
      METHOD: This study used a mixed method research design. Both quantitative and
      qualitative data were collected, but only qualitative findings are presented.
      Eighty-two staff registered nurses responded to a researcher-developed online
      questionnaire. A qualitative content analysis was conducted. Data were
      categorized according to questions then analyzed for key thoughts. Common themes
      were determined. FINDINGS: Findings revealed participants had considered leaving
      the profession, and had considered leaving or had left a nursing unit because of
      poor nurse relationships. Participants identified environmental characteristics
      necessary for good relations. The crucial role nurse managers play in
      establishing good nurse relations was highlighted. Participants cited new
      graduate actions that could enhance relationships with expert nurses.
      Participants also noted missing factors on many nursing units that are essential
      for good nurse-to-nurse relationships. CONCLUSION: Positive nursing relationships
      are the key to establishing a healthy place of work. Only when positive nurse-to
      nurse relationships are established can healthy work environments be created and
      sustained for nurses in the future.

PMID- 23865279
TI  - Relationship between occurrence of falls and fall-risk scores in an acute care
      setting using the Hendrich II fall risk model.
AB  - INTRODUCTION: Falls are a common clinical problem in the acute care setting, and
      fall-related injuries can include fractures, subdural hematomas, excessive
      bleeding, and even death (Hitcho et al., 2004). Several instruments are used
      clinically to estimate a patient's risk of falling. The STRATIFY (Oliver,
      Britton, Seed, Martin, & Hopper, 1997), the Morse Fall Scale (Morse, Black,
      Oberle, & Donahue, 1989), and the Hendrich II Fall Risk Model (Hendrich, Bender,
      & Nyhuis, 2003) are three instruments widely used in clinical practice by nurses.
      To be clinically useful, a fall risk assessment instrument should be easy to use
      with only a small number of items, perform consistently across target
      populations, and have evidence-based scoring and good inter-rater reliability.
      Oliver (2008), author of the STRATIFY tool, questioned the merits of any
      instrument used to assess fall risk in hospital inpatients in the absence of
      interventions to modify the risk factors. Too often, patient assessment and
      assignment of a score become required tasks and resulting data do not drive
      interventions. PURPOSE: The purpose of this study was to explore the relationship
      between scores on the Hendrich II Fall Risk Model (HIIFRM) and fall occurrence as
      recorded in the medical record for patients diagnosed with diabetes mellitus,
      stroke, or heart failure in an acute care inpatient setting. METHOD: To determine
      if a relationship existed between the occurrence of a fall and the HIIFRM score,
      the study used a random sample of patients who fell during admission and a
      matched control group of patients who did not fall. Fall cases were identified
      based on an admission Medical Severity-Diagnosis Related Group (MS-DRG) (Schmidt
      & Stegman, 2008) of stroke or secondary International Classification of Diseases
      (9th revision) (ICD-9) code (Hart, Stegman, & Ford, 2009) of heart failure or
      diabetes. Non-faller matched controls were selected at random from the same
      admission MS-DRG or secondary ICD-9 code as the fall case and matched for
      admission month/year. DISCUSSION: This study found HIIFRM scores to be related
      significantly to falls in the sample of patients with diabetes, but not in the
      sample of patients with heart failure. Although the HIIFRM demonstrated
      statistically significant mean differences in scores between patients who fell
      and those who did not, clinically the instrument failed to identify 44% of
      patients who did fall as being at high risk for falling. Given the negative
      consequences associated with falling, not identifying 44% of high-risk patients
      can have significant clinical implications. CONCLUSIONS: In this study, HIIFRM
      scores were related to falls among inpatients in an acute care hospital who had a
      diabetes diagnosis, but not a heart failure diagnosis. The differ ences between
      patient groups based on medical diagnoses suggest the instrument does not perform
      equally across patient groups, nursing skill levels, or clinical units. Though
      the findings are statistically significant, the clinical concemrn remains that a
      large percentage of patients who fell were scored as low risk using the HIIFRM
      instrument. At some level, every patient admitted to an acute care hospital is at
      risk for falls. Patients sick enough to be in the hospital have underlying
      disease, are receiving physiologically altering medications and treatments, and
      are likely experiencing pain, fatigue, anxiety, sleep disturbance, and other
      symptoms that interfere with cognitive and physical functioning. The key to
      preventing falls among hospitalized patients may lie in addressing how the
      hospital environment creates risk. Nurses should continue to improve the ability
      to assess fall risk and implement interventions that modify or eliminate risk
      when possible.

PMID- 23865280
TI  - The impact of zolpidem on the mental status of hospitalized patients older than
      age 50.
AB  - INTRODUCTION: Although zolpidem is prescribed widely, determining the incidence
      of adverse drug reactions such as mental confusion is of considerable clinical
      importance for nursing practice. PURPOSE: The purpose of this study was to
      examine the use of zolpidem in a hospital setting to determine the incidence of
      mental confusion for patients receiving the drug. METHOD: A correlational cross
      sectional study design was used to examine the effects of zolpidem on
      hospitalized patients. Data abstraction from medical records was used to collect
      demographic and variable information. FINDINGS: The first mental status
      assessment showed no statistical difference of decline in mental status (p=0.08).
      There was, however, a significant change (p<0.000) after the second mental status
      assessment. CONCLUSION: Based on the results of this study, caution must be
      considered for first-time users of zolpidem who are greater than age 50.

PMID- 23865281
TI  - When professional and personal worlds meet: nurse as daughter.

PMID- 23865282
TI  - Floating as a reality: helping nursing staff keep their heads above water.

PMID- 23865283
TI  - Accountability: Is there an app for that?

PMID- 23865284
TI  - Social work and implementation of the Affordable Care Act.

PMID- 23865285
TI  - Part of the job? Workplace violence in Massachusetts social service agencies.
AB  - Workplace violence is a serious and surprisingly understudied occupational hazard
      in social service settings. The authors of this study conducted an anonymous,
      Internet-based survey of Massachusetts social service agencies to estimate the
      incidence of physical assault and verbal threat of violence in social service
      agencies, understand how social service agencies collect data on workplace
      violence, and identify disparities in who is at risk in terms of staff education
      and training level and the work setting. The study gathered general descriptions
      of each agency and compiled incidence data on workplace violence that were
      collected by agencies in fiscal year 2009. The key findings of this descriptive
      study showed high rates of workplace violence against social services providers
      and a pattern of risk disparity, with significantly more risk for direct care
      versus clinical staff. These results are based on data routinely collected by
      social service agencies that typically remain unexamined. A research agenda that
      is sensitive to potential occupational health disparities and focuses on
      maximizing workplace safety in social services is needed.

PMID- 23865286
TI  - Detection of memory impairment in a community-based system: a collaborative
      study.
AB  - The ability to distinguish between older people with cognitive impairment and
      those who age in a healthy manner is crucial because cognitive impairment may be
      a precursor to full-blown dementia. Therefore, an early diagnosis of cognitive
      impairment is important. However, patients are often admitted to a hospital only
      when they already have a serious cognitive impairment. Consequently, cooperative
      studies between clinics and community-based organizations may assist hospitals in
      detecting early cognitive impairment. This article examines how community-based
      organizations can contribute to the early diagnosis of dementia. A cooperation
      model between the Neurology Department of Mersin University Hospital and the
      Mersin branch of the Alzheimer's Association was developed. Trained professionals
      used a neuropsychological battery to evaluate 50 individuals at the Mersin branch
      of the Alzheimer's Association in Turkey. Individuals whose performance fell
      below the average (1 standard deviation or less) were subsequently referred to
      the hospital. On the basis of the neurological and neuropsychological
      assessments, 11 participants were placed in the mild cognitive impairment group
      and 39 were placed in the healthy group. The results suggest that the
      Standardized Mini-Mental State Examination and the Three Words-Three Shapes Test
      are useful tools for detecting early memory impairments in a community-based
      setting.

PMID- 23865287
TI  - Factors leading African Americans and black Caribbeans to use social work
      services for treating mental and substance use disorders.
AB  - This secondary analysis of 5,000 African Americans and black Caribbeans explored
      how their use of social work services to address mental and substance use
      disorders was associated with the disorder involved as well as their perceived
      need for services, belief system, family resources, proximity to services, social
      structural factors, and demographic characteristics. The sample was extracted
      from a national data set. Results of multinomial logistic regression showed that
      use of social work services was increased by dual diagnosis, substance use
      disorder alone, and mental disorder alone; by deteriorating mental health; by
      perceived stigma in treatment use; by welfare receipt and insurance coverage for
      mental health services; and by college graduation. Results also showed that use
      of services outside social work was promoted by dual diagnosis, substance use
      disorder alone, and mental disorder alone; by deteriorating mental health; by
      experience of racial discrimination; by insurance coverage for mental health
      services; by college education or graduation; and by female gender and increasing
      age. The findings' implications for social work intervention and education are
      discussed.

PMID- 23865288
TI  - Use of psychosocial services increases after a social worker-mediated
      intervention in gynecology oncology patients.
AB  - The purpose of this study was to determine whether the introduction of
      psychosocial services to gynecologic oncology outpatients by a social worker
      increases service use. During the initial six weeks (phase I), patients were
      referred for psychosocial services by clinic staff. During the second six weeks
      (phase II), a nurse introduced available services to each patient with a
      brochure. During the final 12 weeks (phase III), a social worker introduced
      services to each patient. The authors then compared psychosocial service referral
      rates. The sample included 196 patients. During phase III, the probability of a
      patient-initiated referral increased 3.4-fold (95 percent confidence interval
      [CI] [1.1, 10.4], p = .04) compared with baseline; the probability of any
      referral rose 2.7-fold (95 percent CI [1.1, 6.3], p = .03). The mean time to
      referral decreased from 79.4 days at baseline to 3.9 days during phase III (p <
      .001). The phase III intervention was accomplished only in 34 patients (39
      percent) because of scheduling conflicts. Of these, eight requested referral,
      resulting in a 24 percent patient-initiated referral rate after meeting with a
      social worker. The introduction of psychosocial services by a social worker to
      gynecologic oncology outpatients increases referral rates and expedites
      evaluation.

PMID- 23865289
TI  - Navigators and assisters: two case management roles for social workers in the
      Affordable Care Act.

PMID- 23865290
TI  - From the Editor.

PMID- 23865291
TI  - Recommendations after non-localizing sestamibi and ultrasound scans in primary
      hyperparathyroid disease: order more scans or explore surgically?
AB  - BACKGROUND: Treatment for primary hyperparathyroidism (PHPT) is surgical
      excision. Sestamibi and ultrasound scans, used to locate hyperfunctioning glands,
      can fail to do so. When both preoperative studies are non-localizing, options
      include 1) referral to a surgeon for a bilateral neck examination or 2)
      additional preoperative imaging. STUDY DESIGN: Retrospective review of patients
      who underwent a parathyroidectomy from January 2010 to December 2011 at the
      University of Mississippi Medical Center (UMMC) was conducted. Only patients with
      negative or inconclusive findings on both sestamibi and ultrasound scans were
      included. The subsequent courses of action and the operative and postoperative
      outcomes were retrospectively reviewed. RESULTS: Negative or inconclusive
      preoperative findings were present in 3 of 26 patients (12%). Additional imaging
      studies were ordered for 1 patient, which also produced nonlocalizing findings.
      All three patients underwent bilateral neck examination (BNE) with intraoperative
      PTH assay. A parathyroid adenoma was found in each case but was found in an
      ectopic location or in the presence of a multinodular goiter. Surgery yielded
      appropriate PTH levels for all 3 patients and each patient was eucalcemic at
      follow-up. CONCLUSIONS: Non-localizing preoperative scans may result from ectopic
      parathyroid adenoma or presence of a multinodular goiter in PHPT. When presented
      with negative preoperative studies, we propose that the patient be scheduled for
      bilateral neck examination with intraoperative PTH assay rather than for
      additional preoperative studies. The surgeon's level of experience with four
      gland exploration and a thorough understanding of normal and aberrant positioning
      of parathyroid glands are imperative for patient safety and treatment, especially
      when localization studies have failed.

PMID- 23865292
TI  - Friends of medicine can make a difference: organize a mini-internship program.
AB  - The mini-internship program cultivates relationships and influence with
      government officials and other important leaders. Because of the educational
      experience of seeing the process of medical practice from the inside, hopefully,
      those who decide how Mississippi health care delivery will be structured are
      better prepared to make those policy decisions. Sample letters are available to
      help get your component society started (@MSMAonline.com). For additional
      infomration about SRH's mini-internship program contact: Cindy Seymour, Singing
      River Medical Society, Telephone (602) 246-8901 or Karen Evers, Managing Editor
      (601) 853-6733. Sample initations, letters, and forms can be found on our
      website: @MSMAonline.com.

PMID- 23865293
TI  - Why is your membership important?

PMID- 23865294
TI  - Going the back way...a southernism.

PMID- 23865295
TI  - [Dysphagia screening on resumption of oral intake in inpatients predictive factor
      for the resumption of oral intake].
AB  - There is much concern about the acute phase of restarting an oral diet for
      hospital inpatients who have been prohibited from any oral intake. We found
      predictive factors for the successful resumption of oral intake in such patients.
      A total of 186 subjects who had been hospitalized without oral intake were
      screened for dysphagia between January 1st and December 31st in 2010 (mean age
      80.9 years), and formed the study population. We observed them from the initial
      consultation day until the discharge. (mean days 32.6) We examined factors of
      age, sex, appetite, gag reflex, tongue activity, the repetitive saliva swallowing
      test (RSST), obeying commands, the status of the laryngopharynx, laryngeal
      sensation and the 3 ml water swallowing test under endoscopy. We excluded those
      who died in hospital after dysphagia screening because they were obviously lost
      to follow-up. One hundred and twelve patients (60.2%) could resume oral intake,
      54 patients could not and 20 (10.8%) died. Logistic regression analysis
      identified seven significant factors in predicting the resumption of oral intake
      : 1) age (p = 0.01, OR = 0.938, 95% CI 0.903-0.976); 2) sex (p = 0.21, OR = 2.15,
      95% CI 1.124-4.128); 3) appetite (p = 0.041, OR = 1.983, 95% CI 1.029-3.821); 4)
      gag reflex (p = 0.06, OR = 1.932, 95% CI 0.971-3.844); 5) tongue activity (P =
      0.002, OR = 3.825, 95% CI 1.647-8.883); 6) RSST (P = 0.013, OR = 2.284, 95% CI
      1.186-4.397); 7) obeying commands (p = 0.02, OR = 3.005, 95% CI 1.507-5.993); 8)
      the status of the laryngopharynx (P = 0.668, OR = 0.668, 95% CI 0.351-1.272); 9)
      laryngeal sensation (P = 0.081, OR = 1.841, 95% CI 0.928-3.650); and the 3 ml
      water swallowing test under endoscopy (P = 0.000, OR = 0.226, 95% CI 0.102
      0.499). These predictive factors could be very useful for dysphagia screening to
      help forecast the successful resumption of oral intake in affected patients. When
      the likelihood of dysphagia and the onset of aspiration pneumonia are suggested
      by dysphagia screening, these factors must be taken into careful consideration
      when oral intake is to be resumed.

PMID- 23865296
TI  - [Office surgery in a private ENT clinic: a statistical analysis of 2,814
      outpatient surgeries].
AB  - All 2,184 outpatient surgeries consisting of 18 surgical procedures were carried
      out for 1,383 subjects in four years from 2008 to 2011 at my clinic. The number
      of subjects undergoing office surgery ranged from 397 cases down to 308 cases per
      year with an annual average of 346 cases. The subjects broken down by the main
      surgical procedures performed comprised 780 cases of myringotomy, 276 cases of
      coagulator ablation of the nasal mucosa, 94 cases of removal of a foreign body in
      the external auditory canal and 92 cases of insertion of the ventilation tube:
      these 4 procedures accounted for about 90% of the total number of patients in my
      practice. The range indications of the other 14 procedures not only included the
      ear, nose and throat, but had spread to the salivary gland, the skin and the
      temporomandibular joint, which demonstrated the necessary skills and flexibility
      of an otorhinolaryngologist. Infants and children between 0 and 11 years old
      consisted about 60% (827/1,383), especially infants between 0 and 5 years old
      accounted for more than 40% (563/1,383), and so suggested the raison d'etre of
      pediatric otorhinolaryngology surgery. On the other hand, subjects over the age
      of 70 accounted for 123 of 1,383 cases (8.9%), and there were three subjects over
      the age of 90, the oldest patient being 99 years old. The male to female ratio
      was 867:516, giving a sex ratio of 1.68. Recently in Japan under the universal
      healthcare system, we must emphasize that office surgery, completing the
      treatment without hospitalization, not only maintains one's expertise as an
      otorhinolaryngologist and has improved the quality of local healthcare, but also
      has contributed to the reduction of medical expenses.

PMID- 23865297
TI  - [A case of early Takayasu's arteritis with initial symptoms of carotidynia and
      fever].
AB  - We report herein on a 15-year-old girl with Takayasu's arteritis (TA) in the
      early pre-pulseless phase who presented with left neck pain and fever. Laboratory
      examination revealed a high level of C-reactive protein (CRP) and an elevated
      erythrocyte sedimentation rate (ESR). Findings of ultrasonography, computed
      tomography (CT), and magnetic resonance imaging and angiography (MRI, MRA)
      demonstrated a thickening of the left carotid artery but neither stenosis nor
      dilation of the large vessels. 18F-fluorodeoxyglucose positron emission
      tomography (18F-FDG PET) after twenty days duration of fever revealed an
      accumulation of 18F-fluorodeoxyglucose not only in the left carotid artery but
      also the wall of the ascending aorta, aortic arch, thoratic aorta, and part of
      abdominal aorta, which led to the diagnosis of TA in the early pre-pulseless
      phase. The patient was treated with prednisolone resulting in a marked
      improvement in both the clinical symptoms and laboratory parameters within a
      couple of weeks. Stenosis of the left carotid artery was found in MRI, MRA
      following four months and a definitive diagnosis was reached. We suggest early
      diagnosis of TA may permit early treatment and improve the prognosis.

PMID- 23865298
TI  - [Subsidized project of hearing aid purchase for mild-moderate hearing impaired
      children in Akita prefecture].
AB  - The dissemination of newborn hearing screening has detected children with mild
      moderate hearing impairment at an early age. However, there is no nation-wide
      welfare system for children with mild-moderate hearing impairment in Japan. Under
      these kinds of social conditions, a subsidized project of hearing aid purchase
      for mild-moderate hearing impaired children has come into force from April 2010
      in Akita prefecture. All 18 candidates who applied for this project were
      subsidized in Akita prefecture. Eighteen children purchased their hearing aids
      using this subsidy. The feature of this project was that every child could have
      access to subsidies as long as their doctor recognized the effectiveness of
      hearing aids because children with hearing impairment need to learn language.
      They contacted the hospital, prefectural government and institutes related to
      hearing loss before this project come into force. We recognized parents who are
      raising a child with mild-moderate hearing impairment have high interest in this
      project. Hearing aids can represent a considerable expense for young parents who
      are raising a child. We encountered some children who had to give up the idea of
      hearing aids due to their parents' economic circumstances before this project
      become effective. These situations were completely avoided after this project
      came into being. This administrative purpose was of demonstrated value in
      children with mild-moderate hearing impairment.

PMID- 23865299
TI  - [Tsallis entropy-based prior for PET reconstruction].
AB  - Maximum a Posteriori (MAP) method has been widely applied to the ill-posed
      problem of image reconstruction. The choice of prior is the crucial point on MAP
      methods. However, the most conventional priors will lead to a blurring of the
      whole image or cause ladder-like artifacts. We therefore proposed a Tsallis
      entropy-based prior for positron emission tomography (PET) iterative
      reconstruction in MAP framework. The method uses a Tsallis entropy-based prior to
      eliminate the uncertainty between prior information and the estimated images. We
      tested this method in the phantom image, compared it with the traditional prior
      methods. the results showed that the proposed algorithm could suppress noise and
      obtain better reconstructed image quality.

PMID- 23865300
TI  - [ECoG classification based on wavelet variance].
AB  - For a typical electrocorticogram (ECoG)-based brain-computer interface (BCI)
      system in which the subject's task is to imagine movements of either the left
      small finger or the tongue, we proposed a feature extraction algorithm using
      wavelet variance. Firstly the definition and significance of wavelet variance
      were brought out and taken as feature based on the discussion of wavelet
      transform. Six channels with most distinctive features were selected from 64
      channels for analysis. Consequently the EEG data were decomposed using db4
      wavelet. The wavelet coeffi-cient variances containing Mu rhythm and Beta rhythm
      were taken out as features based on ERD/ERS phenomenon. The features were
      classified linearly with an algorithm of cross validation. The results of off
      line analysis showed that high classification accuracies of 90. 24% and 93. 77%
      for training and test data set were achieved, the wavelet vari-ance had
      characteristics of simplicity and effectiveness and it was suitable for feature
      extraction in BCI research. K

PMID- 23865301
TI  - [Study on the orientation of liquid crystals presented on the glass substrates
      spin-coated and functionalized with copper ions].
AB  - A stable, uniform, easily implemented, LC-based chemical and biological sensor
      substrate for orientations of liquid crystals (LCs) for a long-term is urgently
      needed for medical applications of the sensors. We proposed a use of spin-coating
      of copper perchlorate (Cu(ClO4)2), with five different concentrations(0
      100mmol/L), directly on glass slides for fabricating a layer of chemically
      sensitive copper ions. Observing the transmitted light with a polarized
      microscope, we found the luminosity of the light propagated through sensors
      deposited with copper ions started to weaken gradually after a certain time. The
      higher was the concentration of copper ions covered on the glass substrates of
      the sensors, the faster the weakening occurred, and the less time was needed for
      transmitted light to turn completely dark. But there was no change in luminosity
      of the transmitted light for the sensors without Cu(ClO4)2 spin-coating even
      after stored at room temperature (25 degrees C) for a whole day. When the
      Cu(ClO4)2 deposited sensors were stored within a drying oven at room temperature
      (25 degrees C) for 2 months, it was found that there vas almost no change in
      luminosity of the transmitted lights. The results showed that all the thin films
      of LC on glass slides functionalized with Cu(ClO4)2 could keep homeotropic and
      stable orientation for a long time; the concentration of Cu (ClO4)2I has an
      influence on the orientation response speed of LC from planar to perpendicular
      orientation.

PMID- 23865302
TI  - [A study of brain-computer interface paradigm based on mental arithmetic].
AB  - In the traditional P300 brain-computer interface (BCI) system, the
      electroencephalogram (EEG) signals can only provide limited information with a
      low signal-to-noise ratio. A BCI paradigm under visual stimulus was proposed in
      our study aiming to effectively activate the related brain areas and response
      signal while dealing with specific cognitive task (mental arithmetic task), so as
      to enhance the EEG signals. The result was compared with the traditional P300
      counting task paradigm. Then the collected EEG data were preprocessed including
      extracting signal features with coherent averaging method, and analyzing the
      influences of different experimental paradigms on main components of event
      related potential (ERP). In the improved paradigm experiments the average
      increasing rate of P300 amplitude was 6. 83MV (73. 94%). The brain activity from
      400ms was more active and lasted longer. Besides, unlike traditional counting
      task, mental arithmetic task appeared to have apparent activation at 650ms. The
      results showed that the improved paradigm could activate the related brain areas
      better and enhance the characteristics of signal. This provides a new system
      paradigm for BCI.

PMID- 23865303
TI  - [Studies of visual mismatch negativity elicited by cartoon facial expressions].
AB  - A modified "cross-modal delayed response" paradigm was used to investigate
      whether the visual mismatch negativity can be elicited by cartoon facial
      expressions, and to define the mechanism underlying automatic processing of
      facial expressions. Subjects taking part in the tests were instructed to
      discriminate the type of the tones they heard as quickly and accurately as
      possible, and to act merely when they heard the response imperative signal.
      Neutral, happy and angry faces were presented during intervals between a tone and
      a response imperative signal. Visual mismatch negativity (VMMN) was obtained by
      subtracting the event - related potential (ERP) elicited by neutral faces from
      that elicited by happy faces or angry faces. The angry-related VMMN was more
      negative than happy-related VMMN, and both were more negative in the left than in
      the right cerebral hemisphere. The results indicated that VMMN can be elicited by
      the cartoon facial expressions, and the facial expressions can be processed
      automatically.

PMID- 23865304
TI  - [Research on infrared radiation characteristics of skin covering two acupuncture
      points in the hand and forearm, NeiGuan and LaoGong points].
AB  - In order to research the infrared radiation characteristics of the skin covering
      Traditional Chinese acupuncture points, which are NeiGuan in the forearm and
      LaoGong in the center of the palm, we detected continuously the infrared
      radiation spectra of the human body surface by using Fourier Transform Infrared
      Spectroscopy. The experimental results showed that firstly, the differences of
      the infrared radiation spectra of the human body surface were obvious between
      individuals. Secondly, the infrared radiation intensity of the human body surface
      changed with time changing. The infrared radiation intensity in two special
      wavelength ranges (wavelengths from 6. 79 microm to 6. 85 microm and from 13. 6
      microm to 14. 0 microm) changed much more than that in other ranges obviously.
      Thirdly, the proportions of the infrared radiation spectra changed, which were
      calculated from the spectra of two different aupuncture points, were same in
      these two special wavelength ranges, but their magnitude changes were different.
      These results suggested that the infrared radiation of acupuncture points have
      the same biological basis, and the mechanism of the infrared radiation in these
      two special wavelength ranges is different from other tissue heat radiation.

PMID- 23865305
TI  - [3D liver vessel segmentation based on hessian matrix and GMM-EM algorithm].
AB  - An accurate segmentation of vascular systems is fundamental for many medical
      applications. In this paper, we propose a 3D vessel enhancement and extraction
      method. It is based on the analysis of Hessian matrix and Gaussian mixture model
      expectation-maximization (GMM-EM) algorithm. Firstly, tube-like vessels were
      detected and enhanced based on the Hessian matrix eigenvalues. And then, the
      vascular system was segmented, and then a rough system was obtained with GMM-EM.
      Hessian-based filters were found to be sensitive to noise and sometimes gave
      discontinued vessels. Hence, we utilized the closing operation to avoid
      discontinuity and a 3D-filter on the segmented vessels to reduce noise brought by
      the contrast agent. Finally, a searching method based on spatial connected area
      is presented to connect the vascular system in 3D. The experimental results
      illustrated the efficiency of the method for 3D liver vessel segmentation
      proposed in this paper.

PMID- 23865306
TI  - [Diagnostic value of intraluminal contrast enhanced ultrasonography in evaluation
      of gastrointestinal stromal tumors].
AB  - The aim of the present study was to investigate the diagnostic value of the
      contrast-enhanced ultrasonography for gastrointestinal stromal tumors (GISTs).
      The conventional transabdominal ultrasonography and contrast-enhanced
      ultrasonography using an intraluminal contrast agent were performed in 66 cases.
      The different diagnostic value between conventional transabdominal
      ultrasonography and contrast-enhanced hydrocolon ultrasonography was compared,
      including the depiction ratio and location accuracy. The morpholpgical features
      of GISTs were observed. The sensitivity of the contrast-enhanced hydrocolon
      ultrasonography in the depiction of the GISTs (57/66, 86.4%) was higher than that
      of the conventional transabdominal ultrasonography(33/66, 50%, P<0. 05).
      Furthermore, the accuracy of the contrast-enhanced ultrasonography in the
      location of the GISTs (52/57, 91. 2%) was higher than that of the conventional
      transabdominal ultrasonography (13/33, 39. 4%, P<0. 05). The GISTs with higher or
      lower risk have different ultrasonic features. The contrast-enhanced
      ultrasonography was a more valuable diagnostic method for GIST than the
      conventional transabdominal ultrasonography.

PMID- 23865307
TI  - [Research on non-contacting ECG measurement and filtering method].
AB  - Non-contact measurement is an effective method of long time measurement of human
      electrocardiograph (ECG) signal. Because the relative position between measuring
      electrode and human body is not fixed, this method could result in constant
      changes of ECG signal collection. It often appears ECG signal distorting and
      weakened in filtering. This paper, using the principal component analysis (PCA)
      basic theory, proposes a fast adaptive PCA denoising algorithm which can
      automatically adjust the parameters according to the changes of ECG signal. The
      experiment proved that PCA denoising could be barely impacted by signal changes
      and can disposably remove interference signal on the premise of keeping the main
      features of ECG signal and can prevent ECG signal from being weakened in
      filtering at the same time.

PMID- 23865308
TI  - [Primary study of the threatening of unfixed planning of image guided
      radiotherapy to the volume margin of neck tumor].
AB  - Some patients who have neck tumor but cannot tolerate the thermoplastic
      immobilization may be supported by simple cushions, and are marked on the neck
      skin during CT simulation. We therefore set 5 mm as the spinal cord-planning risk
      volume margin in the intensity-modulated radiotherapy plans in our Centre. Cone
      beam CT (CBCT) scans were acquired for three times, and matched with the
      simulation CT images in each radiotherapy. The mean and the standard deviation of
      the individual, the root mean-square and the standard deviation of the individual
      were calculated. The matched results of the third CBCT were used to calculate the
      spinal cord- planning risk volume margin. The results showed that the
      interfraction error was significantly reduced and the intrafraction error was
      stable by CBCT guiding. CBCT and 5 mm spinal cord-planning organ is feasible and
      safe without threatening volume margin to high dose radiotherapy for the patients
      with neck tumor and not able to tolerate thermoplastic immobilization.

PMID- 23865309
TI  - [Value of dual-source CT in diagnosis of single ventricle].
AB  - This paper was aimed to explore the features of single ventricle with dual source
      computed tomography (DSCT) and the value of the modality in diagnosis of the
      single ventricle disease. Dual-source computed tomography imaging of 14 cases of
      single ventricle compared with the results of surgery and cardiac catheter were
      retrospectively analyzed. Firstly, 14 cases were classified into three types
      according to Anderson classification method, including 7 cases(50. 0%) left
      ventricular type, 3 cases(21. 4%) right ventricular type and 4 cases (28. 6%)
      undecided ventricular type. Secondly, in accompanying malformation respect,
      pulmonary stenosis, bilateral superior vena cava, atrial septal defect (ASD) and
      common atrioventricular valve were presented frequently. Thirdly, affiliated
      cardiac chamber of left ventricular type were mostly in front of the major
      cardiac chamber (5 cases,71. 4%), while affiliated cardiac chamber of right
      ventricular type were behind of the major cardiac chamber totally. Fourthly, more
      than half of aortas and pulmonary arteries stemming from common cardiac chamber
      can be seen (8 cases, 57. 1%). Meanwhile the aorta valves were more on the right
      of pulmonary valve (9 cases, 64. 3%). The classification of 10 cases of single
      ventricle was compared with the results of surgery, and the coincidence rate is
      100%. DSCT can diagnose the single ventricle disease accurately. The aorta,
      pulmonary artery and coronary artery can be displayed completely and
      simultaneously as well.

PMID- 23865310
TI  - [Evaluating the left ventricular global systolic function of patients with
      diabetes mellitus by the real-time three-plane speckle tracking imaging].
AB  - Our study was aimed to evaluate the left ventricular (LV) global longitudinal
      systolic function of patients with diabetes mellitus (DM) using real-time three
      plane speckle tracking imaging (RT-3P STI). The case group was the patients of
      type 2 DM with normal LV ejection fraction (EF). Then according to glycated
      hemoglobin (HbAlc) control level, the case group was divided into two groups,
      including DM1 (HbAlc<7%, n=31) and DM2 (HbAlc >or=7%, n= 37); 63 matched
      volunteers were chosen as control group. Conventional measurements of the LV size
      and function were performed. We then applied the automatic function imaging to
      analyze the global longitudinal systolic peak strain (GLPS) of the three apical
      views online, including the GLPS of apical four chamber view (GLPS-A4C), the GLPS
      of apical two chamber view (GLPS-A2C), the GLPS of apical long axis view (GLPS
      LAX), and then generating the average GLPS (GLPS-Avg). The experimental results
      showed that there was no statistical difference in clinical baseline
      characteristics among the three groups (P>0.05). However, there were statistical
      differences in the ventricular wall thickness and the LV mass index of the DM1
      and DM2 groups compared with that of the control (P<0. 05). No significant
      differences were found in LV diameters, volumes, LVEF among the three studied
      groups (P>0. 05). We also found significant differences in GLPS-LAX, GLPS-A2C,
      GLPS-Avg when we compared DM2 group with those of the DM1 group or the control
      (P<0. 05). We found a statistical difference in GLPS-A4C only when we compared
      the DM2 group with the control(P<0. 05), and no statistical difference in the
      strains of the three views between DM1 group and control (P>0. 05). RT-3P STI
      could not only accurately be used to evaluate the LV global longitudinal systolic
      function, but could also reflect the reduction of sub-clilical systolic function
      in DM patients with poor blood glucose control in the early stage.

PMID- 23865311
TI  - [Investigation on the relationship between seat heights and performance during
      the sit-to-walk movement].
AB  - DLUT4060 piezoelectric multi-component force platforms and DVM8820 three
      dimensional infrared image capture system were used to test the sit-to-walk (STW)
      movements of 11 healthy elderly (72. 6 +/- 12. 2 years old) and 11 healthy young
      (19. 7 +/-1. 3 years old) individuals. Firstly, we studied the effects of seat
      heights on the ground reaction forces, the velocity of the center of mass, and
      action time duration. Then we discussed the movement strategies and falling risks
      of the persons in the two age groups respectively. Finally, we decided the best
      seat height for the two age groups. It was found that the best seat heights for
      both the two age groups were 100% popliteal height. This height may make the
      subject get the greatest biomechanical advantages and the lowest falling risks.
      The popliteal height must be concerned when designing and fixing up the public
      activity area facilities and daily life of the elderly. To some extent, it can
      reduce the falling risk of the elderly.

PMID- 23865312
TI  - [Study on plantaer pressure distribution of people walking with different
      backpack load].
AB  - The purpose of this study was to investigate the effect of different backpack
      load on the plantar pressure of people during walking. By using three-dimensional
      force platform system, we collected the ground reaction force data from 20
      college students, who were carrying different loads on their backs, and then we
      transformed the data into a characteristic two-peak curve. Seven characteristic
      parameters on the curve were selected and analyzed by using statistical methods.
      The results indicated that the peak ground reaction forces increased as the loads
      increased. Furthermore, in consideration of different genders, the amount
      increased was different. For the male subjects, when backpack load reached 17%
      body weight, changes in ground reaction force began to take place until the
      backloads reached 20% body weight changes in ground reaction force induced a
      significant difference. Por the female subjects, changes in ground reaction force
      began to take place with loads up to 14% body weight and while it reached 15%
      body weight it induced a significant difference.

PMID- 23865313
TI  - [Effect of Pinch-3 gene interference of glomerular podocytes on cell morphology
      and cell traction force].
AB  - Pinch-3 protein is an important constituent of cell membranes, which directly
      affects the cell morphology and mechanical properties. We observed and compared
      the change of morphology and cell traction force of glomerular podocytes before
      and after Pinch-3 gene inhibition by gene interference technology in this
      experiment. We found that a number of pores appeared on the cell surface, and the
      cell projected area were increased at the same time, with an approximate average
      about an increase of 40% after Pinch-3 gene inhibition. The results showed that
      the cell traction force of glomerular podocytes was significantly reduced, with
      an approximate average decrease of 40%, the maximum value of the cell traction
      force was reduced and the distribution of cell traction force became dispersive.
      All this suggested that after Pinch-3 gene inhibition, some pores created on the
      cell surface influenced the physical properties of glomerular podocytes and then
      affected the cell projected area and influenced the formation and distribution of
      cell traction force of the glomerular podocytes as well.

PMID- 23865314
TI  - [Design and realization of training methods based on sit-to-stand balance ability
      training apparatus].
AB  - In this research, a new set of training methods was created and put into practice
      to train the body's sit-to-stand balancing ability, and controlling ability of
      body's gravity centre of patients with cerebrovascular diseases. It contains a
      series of motion trainings, including sitting position training, standing
      position training, sit-to-stand training and game training, etc. There is also a
      series of trainings of feedback included in this set of methods, such as internal
      feedback, external feedback, bandwidth feedback, conclusive feedback, visual
      feedback, acoustical feedback and so on. The trainings resulted in better
      controlling ability of body's centre of gravity in the sit-to-stand process of
      patients after a period of training. It indicated that these targeted-designed
      trainings, especially the feedback trainings, could effectively help the under
      trained patients to have a better knowledge of their current situation, and in
      turn to have a better knowledge of which aspects they should take more training
      to achieve a better therapeutic effect.

PMID- 23865315
TI  - [Three-dimensional displacement of implant-supported cantilever fixed partial
      denture under oblique loading].
AB  - The purpose of this study was to research the three-dimensional displacements of
      implant-supported cantilever fixed partial denture (CFPD) under oblique loading.
      One Beagle dog was used in this experiment. Two immediate implants of ITI were
      inserted in the mandible of the dog, and the implant-supported CFPD which used
      the implants as abutments was made in vitro fresh mandible. Then the digital
      laser speckle technique was employed to measure the three-dimensional
      displacements of CFPD under different oblique loading. We found that when an
      oblique loading was exerted on the pontic, the displacement increased with
      increasing of load. Under equal loading, the displacement of the abutment near to
      the pontic was smaller than that of the pontic but greater than that of the abut
      ment far from the pontic. When oblique loading was exerted on the abutment, the
      displacement of the direct loaded abutment was greater than that of the other
      abutment and the pontic. Under the.eeual loading, the displacement of implant
      supported CFPD of loading on pontic was greater than that of loading on
      abutments. The experiments demonstrated that implant-supported cantilever fixed
      partial denture (CFPD) is an effective and advisable therapy for totally? or
      partially edentulous patients. However, it is also suggested that the clinicians
      should avoid exerting oblique loading, especially the obliqe loading of the
      pontic when th e CPDF is used.

PMID- 23865316
TI  - [Comments and suggestions on the medical device standardization system from the
      view point of medical devices test].
AB  - Medical device test is a very important step of medical device registration
      processes and is also a procedure to confirm whether the medical devices comply
      with applicable standards. The standardization system is imperfect yet in China
      due to the complexity of medical devices and the specialty of medical device
      industry. In this circumstance, the medical device standard is not only the
      important criteria for the medical devices registration, but also an important
      practical procedure of the medical device registration. This paper reviews the
      existing questions and also gives some comments and suggestions on the medical
      device standardization system from the view point of medical device test.

PMID- 23865317
TI  - [Long-term anti-cancer implants inhibiting the activity of tumor growth in animal
      models].
AB  - This study was aimed to establish rat bladder tumor animal models to investigate
      the in viva antitumor effect of polyanhydride-pirarubicin (PAD-THP), a long
      lasting anti-cancer implant, in the bladder tumor of animal models. The model of
      bladder cancer was set up with N-butly-N-(4 hydroxybutyl) nitrosamine (BBN)
      feeding into rats. The PAD-THP long-acting anti-cancer implants containing the
      drugs and the same dose of the THP naked drug were placed under the bladder
      mucosa of bladder tumor model in vivo. The pirarubicin plasma concentration was
      measured with high performance liquid chromatography (HPLC) detection in vivo.
      The effective drug concentration and lasting period were observed and compared in
      the animal bodies. The tumor sizes were measured before and after the treatment.
      The in viva antitumor effects were analyzed and compared. The results showed that
      more significant antitumor effect of PAD-THP implants on the local drug release
      characteristics were presented compared with that of the same dose of THP bare
      drug group and there were significant differences (P<0. 05) between the two
      methods. All the results indicated that the PAD-THP anti-cancer implants in the
      postoperative local treatment of bladder tumors would show prosperous in the
      future for clinical application.

PMID- 23865318
TI  - [Effects of electrical stimulation on the differentiation of mesenchymal stem
      cells into cardiomyocyte-like cells].
AB  - The aim of this study is to investigate the effects of electrical stimulation ES)
      on the induction of rat bone marrow mesenchymal stem cells (rBMSCs) to
      differentiate into cardiomyocyte-like cells in vitro. The third or fourth
      generation of the rBMSCs was randomly divided into three groups, i. e. ES group,
      5-Azacytidine (5-Aza) group, and control group. Those in the ES group with
      complete medium were exposed to 1,2,4 and 6V, 2Hz, 5ms ES for 2h everyday,lasting
      for 10d. Those in the 5-Aza group were induced by 10 micromol/L 5-Aza for 24h,
      then the medium was changed to complete medium without 5-Aza. Those in the
      control group were only cultured with complete medium. The growth status and
      morphological features of rBMSCs were observed by inverted phase microscope. The
      mRNA expressions of GATA4, a-actin, ACTN2 and TNNT2 were determined by Real-time
      fluorescent quantification PCR, and the protein expression of TNNT2 was detected
      with immunofluorescence staining. The results showed that the mRNA expression
      level of the GATA4, a-actin, ACTN2 and TNNT2 and the protein expression level of
      the TNNT2 were significantly higher in the ES group and 5-Aza group, compared to
      those in the control group(P<0. 05). It suggested that ES could induce rBMSCs
      differentiation into cardiomyocyte-like cells in vitro.

PMID- 23865319
TI  - [Effect of sinusoidal electromagnetic fields on rats femur tissue cultivation in
      vitro].
AB  - The present research was aimed to investigate the effect of 50Hz, 1. 8mT of
      sinusoidal electromagnetic fields(SEMFs)on femur tissue cultivation in vitro. The
      rat femur tissue was isolated from SD rats by method of enzyme digestion, and
      randomly divided into two groups: SEMFs group and control. The femur tissue of
      SEMFs groups were exposured under 50Hz 1. 8mT of SEMFs for 1. 5h/time/d, but
      those in the control groups were without SEMFs treatment. The correlative gene
      was detected by the Real-time RT-PCR that after SEMFs treatment for 0 (first
      times treatments is 0 days), 1, 2, 3, 4 and 5d. The alkaline phosphatase (ALP)
      activity was measured after SEMFs treatment for 3, 6, 9 and 12d respectively. The
      calcium content was detected after SEMFs treatment for 3, 6, 9 and 12d. The
      results showed that the OPG and Collagen-1 mRNA expression level was kept at a
      relatively stable level by SEMFs in the SEMFs group significantly. The Runx-2
      mRNA expression level was significantly increased after the SEMFs treatment for
      1d and 5d. The ALP activity of femur tissue was significantly increased alter
      SEMFs treatment for 3d and 9d. The calcium content was higher than untreated
      groups after SEMFs treatment for 6, 9 and 12d. The SEMFs promoted OPG, Collagen
      1, Runx-2 mRNA expression level, ALP activity and calcium content. The result
      indicated that SEMFs increased the metabolism activity of femur tissues.

PMID- 23865320
TI  - [Study on FAK regulation of migration of vascular endothelial cells depending
      upon focal adhesion proteins].
AB  - Tumor angiogenesis induced by vascular endothelial cells (VECs) migration is a
      necessary condition for tumor growth and metastasis. The purpose of this study is
      to investigate the effect of focal adhesion kinase (FAK) inhibitor (50nmol/mL) on
      the adhesion and migration of endothelial cells(ECs) and the expression of focal
      adhesion proteins vinculin, talin and paxillin. Scratch wound migration assay was
      performed to examine the effect of FAK inhibitor with 50nmol/mL on ECs migration
      at 0, 5, 10, 30, 60 and 120min, respectively. And immunofluorescence analysis was
      performed to detect the expression of F-actin in ECs treated with FAK inhibitor
      within 2h. Western blot was carried out to determine the effect of FAK inhibitor
      on expression of vinculin, talin and paxillin proteins. The results showed that
      the migration distance and the expression of F-actin in ECs treated with FAK
      inhibitor decreased significantly compared with that of the controls, and the
      level of vinculin showed no significant difference with increasing of treated
      time of FAK inhibitor. However, the talin and paxillin showed an identical
      decreasing tendency in 5-10min, but slowly going up in 30min and then after
      subsequently decreasing. The results of this study proved that blocking
      phosphorylation of FAK could inhibit VECs adhesion and migration by
      downregulating focal adhesion proteins so that it may inhibit tumor angiogenesis.
      This may provide a new approach for tumor therapy.

PMID- 23865321
TI  - [Characteristics of JC virus VLP-Z for targeting gene delivery].
AB  - The characteristics of virus-like particle (VLP) of JC virus (JCV) as a vector
      for targeting gene delivery was determined. The exogenous DNA (PUC19) packaged in
      VLP-Z was resistant to DNase I. VLP-Z was able to deliver a reporter plasmid
      pEGFP-N1 into HeLa cells and the green fluorescent reporter protein was expressed
      in these cells. VLP-Z was also able to bind IgG by interaction with the Z
      fragment of VLP-Z and IgG. These results suggested that VLP-Z might be used as a
      vector to deliver therapeutic genes to target cells with incorporating IgG
      antibodies.

PMID- 23865322
TI  - [Preparation of cytoplasts from HL-60 cells].
AB  - This experimental research was aimed to establish an optimum system of
      enucleation, purification and identification for preparing the cytoplasts of
      suspension culture cells in order to undertake cell recombination. Human leukemia
      HL-60 cells in suspension culture were purified by 42% Percoll density gradient
      centrifugation and low-speed centrifugation at 1 500r/min, respectively. The
      purified HL-60 cells were treated with cytochalasin B (CB) alone or combined with
      colcchicine and enucleated by isopycnic gradient centrifugation on 50% Percoll at
      25 degrees C and 34 degrees C, respectively. Cytoplasts made from HL-60 cells
      were purified through gradient centrifugation by 37%, 38% and 40% Percoll,
      respectively. The final cytoplasts were identified by Wright-Giemsa staining and
      4,6-diamidino-2-phenylidole dihydrochloride (DAPI)/5, 6-carboxyflu-orescein
      diacetate succinimidyl ester (CFSE) double-staining. The phenotype and
      mitochondrial membrane potential of HL-60 cytoplasts were analyzed by flow
      cytometry. The results indicated that the enucleation ratio of HL-60 cells
      induced by CB combined with colcchicine was up to 91. 98% +/-4. 29%, which was
      significantly higher than that in CB alone group (74. 95% +/- 3. 02%)(P<0. 01).
      The rates of enucleation and cytoplast with diameter over 5min in 34 degrees C
      group were higher than those in 25 degrees C group (all P<0. 01). The cytoplast
      purities were (95.43 +/- 0. 59)% in 38% Percoll groups,which were higher than
      those of 40% Percoll (P<0. 05). Nucleus and caryoplasm could be clearly
      distinguished by DAPI and CFSE double labeling. The results further showed that
      the phenotype of HL-60 cytoplasts had no significant change, and the activity of
      the cytoplasts was above 80% within 12h. It is concluded that enucleation throuth
      density gradient centrifugation on 50% Percoll mediated by CB combined with
      colcchicine, 38%Percoll of purification followed by DAPI/CFSE double labeling and
      MMP detection is an optimum scheme for preparation and identification of
      cytoplast from suspension culture cells.

PMID- 23865323
TI  - [Construction of Runx1 transgenic mice].
AB  - This study was aimed to construct transgenic mouse model with target for Runxl
      gene. Runxl cDNA of mice was amplified by PCR from pcDNA3. 1 Flag Runx1 FL vector
      and inserted into ptetO7-Asc-IRES-EGFP vector to form a recombinant vector, and
      then the recombinant vector was injected into fertilized egg by microinjection
      technology to get a transgenic mouse. The results of PCR and Southern blot
      indicated that the Runx1 transgenic mouse was constructed successfully, and this
      could provide an important tool for studying the function of Runxl gene in vivo.

PMID- 23865324
TI  - [Study on the effect of Klotho gene interferred by plasmid-mediated short hairpin
      RNA (shRNA) on sinoatrial node pacing channel gene].
AB  - The study was aimed to assess the effect of Klotho gene and sinoatrial node
      pacing channel gene (HCN4 and HCN2) for studying sick sinus syndrome, with Klotho
      gene under the interference of Plasmid-mediated short hairpin RNA. Twenty-five
      C57BL/6J mice were divided into four groups, i. e, plasmid shRNA 24h group,
      plasmid shRNA 12h group, sodium chloride 24h group and sodium chloride 12h group.
      Plasmid shRNA 50microL (1microg/microL) and sodium chloride 50microl were
      respectively injected according to mice vena caudalis into those in plasmid shRNA
      group and sodium chloride group. After 12h or 24h respectively, all mice were
      executed and their sinoatrial node tissues were cut. The mRNA of Klotho, HCN4 and
      HCN2 gene were detected by RT-PCR. The results of RT-PCR showed that Klotho, HCN4
      and HCN2 mRNA levels were lower compared with those in sodium chloride 12h group
      after 12h interference interval. The results indicated that there might be the a
      certain relationship between Klotho gene and sinoatrial node pacing channel gene.

PMID- 23865325
TI  - [Experimental study of effect of low power laser on telomere length of cells].
AB  - To investigate the effect of low power helium neon laser (He-Ne laser) on the
      telomere length of human fetal lung diploid fibroblast (2BS) cell, we used the
      laser (gamma = 632. 8 nm, P = 2 mW) to treat the young 2BS cells. Cell growth and
      proliferation was observed through MTT method after treating with low power
      laser. The relative telomere length of 2BS cells was detected by fluorescence
      real-time quantitative PCR (q-PCR). The results showed that the cells of the
      treated groups grew better than the untreated groups. The telomere DNA length of
      the old 2BS cells, treated by low power He-Ne laser when they were young, was
      longer than that of untreated group. The results of the present study indicated
      that the low power He-Ne laser might decrease shortening rate of telomere and
      delay the aging of cells. Therefore, this study provides the experimental basis
      for us to further investigate the effect of low power laser on cell aging at the
      gene level.

PMID- 23865326
TI  - [Comparison of clinical features between fulminant type 1 diabetes and classical
      autoimmune type 1 diabetes].
AB  - The data of 1,265 in-patients with diabetic ketosis or ketoacidosis treated in
      West China Hospital from October 2005 to October 2011 were analyzed
      retrospectively, and 8 of whom met fulminant type 1 diabetes (F1D) diagnostic
      criteria. The clinical features of the 8 F1D patients were investigated and
      compared with other 16 newly diagnosed autoimmune type 1 diabetes (T1D) patients,
      gender- and age-matched and with acute onset of ketoacidosis. During the six
      years between 2005 and 2011, the incidence of FID was 6.3 per thousand (8/T265)
      among all patients with diabetic ketosis or ketoacidosis admitted to the West
      China Hospital. The averaged age of the patients at onset of F1D was (30. 1 +/-
      9. 7) years old, and the duration of diabetes was (4. 0 +/- 2. 4) days. Five of
      the 8 F1D patients had flu-like symptoms, and 7 had gastrointestinal symptoms.
      Blood glucose of F1D patients on admission was significantly higher than that of
      autoimmune T1D patients (P<0. 01), while the glycated hemoglobin (HbAlc) was
      lower than that of autoimmune T1D patients (P<0. 01). Additionally, fasting and
      postprandial C-peptide was significantly lower in F1D patients, with more severe
      acidosis, electrolytes and acid-base disturbances. The data suggest, that,
      compared with the autoimmune T1D patients, F1D patients have more complicated and
      more severe clinical manifestation with more severe hyperglycemia, more
      significant insulin deficiency and more obvious fluid electrolytes and acid-base
      disturbances. However, the sensitivity and the specificity of the diagnostic
      criteria of F1D are still needed to be improved for the Chinese people, so more
      multi-center and large-scale clinical trials should be conducted in the future.

PMID- 23865327
TI  - [Research on effects of bone marrow mononuclear cells implantation on model of
      experimental pulmonary artery hypertension].
AB  - In the present study, we carried out intratracheal administration of bone marrow
      derived mononuclear cells (BM-MNCs) to dehydromonocrotaline (DMCT)-induced canine
      pulmonary artery hypertension (PH) of rat model to examine the security and
      feasibility, and the aim was to discuss the mechanism. All animals (n=30) were
      randomly divided into 3 groups (n=10 in each group), i. e. control group, PH
      group and BM-MNCs group. Six weeks after the transplantation, the hemodynamic
      data and right ventricle weight ratio were significantly improved for those in BM
      MNCs group compared with those in PH group. The lung mRNA levels of vascular
      endothelial growth factor (VEGF) were higher, while preproendothelin-1 (ppET-1),
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were lower
      compared with those in the PH group (P<0. 05). Immunofluorescence and
      histochemical results confirmed that 6 weeks after the administration,
      transplanted BM-MNCs were still alive and could differentiate into pulmonary
      vascular endothelial cells. These results showed that intratracheal
      administration of BM-MNCs could obviously reduce or even reverse the DMCT
      induction of PAH process. The mechanism could be explained as that the function
      was mainly through the paracrine effect to promote renewable and reduce
      inflammation.

PMID- 23865328
TI  - [Comparison of dexmedetomidine and midazolam on neurotoxicity in neonatal mice].
AB  - Dexmedetomidine and midazolam have been widely used in clinical anesthesia and
      intensive care unit sedation. These two drugs differ in sedative mechanism. We
      hypothesized that the neurotoxicity of repeated exposure to dexmedetomidine or
      midazolam for neonatal mice might be different. Twenty four mice of postnatal day
      8 were randomly divided into control (n=8), dexmedetomidine (n=8) and midazolam
      group (n=8) respectively. In the three groups, saline(10mL/kg),
      dexmedetomidine(10microg/kg) or midazolam(40mg/kg) was injected intraperitoneally
      once a day, in the next five days, respectively. Then the brains of the mice in
      the three qroups were removed and cryosectioned. Apoptotic neural cell in
      hippocampus region was detected with terminal deoxynucleotydyl transferase 
      mediated dUTP nick end labeling(TUNEL). Bcl2 and Bax protein expression level in
      the hippocampus were determined by immunofluorescent staining. In the present
      study, the number of TUNEL-positive cells from midazolam group ((20 +/-3) /mm2)
      was larger than that from dexmedetomidine group ((15+/-2) /mm2, P<0. 05) and
      control group((13+/-3) /mm2, P<0. 05); Bcl-2 protein quantity in hippocampus from
      control group((790+/-103)/mm2)was significantly lower than that in midazolam
      group((1187+/- 162)/mm2, P<0.05)and dexmedetomidine group((890+/-125)/mm2, P<0.
      05). Bax protein level in control group((942+/-104)/mm2) was also significantly
      lower than that in midazolam group((1839+/-160)/mm2, P<0. 05)and dexmedetomidine
      group((1143+/-125)/mm2, P<0. 05); Bax/Bcl-2 ratio in midazolam group(0. 64+/-0.
      13) was significantly lower than that in dexmedetomidine group(0. 78 +/-0. 14,
      P<0. 05) and control group(0. 84+/-0. 15, P<0. 05). Our results suggest that
      dexmedetomidine has lower neurotoxicity than midazolam for neonatal mice.

PMID- 23865329
TI  - [Design of minimally invasive surgery wrist institution actuated by shape memory
      alloy].
AB  - The rapid development of minimally invasive surgery technology requires higher
      flexibility of surgical treatment and small volume of medical instrument. This
      paper proposed a new type of minimally invasive surgery wrist institution
      actuated by TiNi shape memory alloy (SMA) wire. The wrist institution has some
      advantages such as compact structure, flexible function, light weight, big
      movement space, and high output position precision. The paper briefly introduces
      the properties of TiNi SMA and describes the configuration of wrist institution.
      We also carried out mechanism simulation analysis to the mechanics model and set
      up kinematics equations, and finally presented the workspace of the institution.

PMID- 23865330
TI  - [ECG QRS signal detection and control system design of ventricular assist
      device].
AB  - In order to achieve auxiliary timing of ventricular assisting device to
      automatically track the ECG signals, we designed a set of ECG acquisition circuit
      in our study for the first time. Then we carried out ECG acquisition, smoothing
      filter and QRS detection on the LabVIEW. With the QRS signal as a benchmark, the
      control system immediately triggered ventricular assisting device to trigger the
      heart to contract for ejection for about 300 ms, and then to assist to make it
      relax. The practical effects of the experiment proved that ECG acquisition
      circuit had the feature of strong anti-interference, and control system had no
      false QRS detection and no false triggering of assist device. This achieves the
      auxiliary timing which could automatically track the ECG signal.

PMID- 23865331
TI  - [Development of a new type intelligent high potential therapeutic apparatus].
AB  - This article presents the development and design of a new type intelligent high
      potential therapeutic apparatus, by using Atmega1280 as its controller. The
      circuit transforms voltage from 220 V ac to 110 V ac and constitutes different
      circuits with relays. In order to get different treatment waveforms, inductance
      of various values is used in different circuits. The circuit generates
      appropriate treatment voltage with the transformer booster. Simultaneously, the
      corresponding control software was composed. Finally the hardware and software
      designs of the high potential therapeutic apparatus were completed. Result of the
      experiment showed that the high potential therapeutic apparatus worked steadily
      and the effect of treatment was satisfactory.

PMID- 23865332
TI  - [A method of synthesizing cicada sound for treatment of tinnitus].
AB  - Masking therapy can make patients accustom to tinnitus. This therapy is safe and
      easy to implement, so that it has become a widely used treatment of curing
      tinnitus. According to surveys of tinnitus sounds, cicada sound is one of the
      most usual tinnituses. Meanwhile, we have not hitherto found published papers
      concerning how to synthesize cicada sound and to use it to ameliorate tinnitus.
      Inspired by the human acoustics theory, we proposed a method to synthesize
      medical masking sound and to realize the diversity by illustrating the process of
      synthesizing various cicada sounds. In addition, energy attenuation problem in
      spectrum shifting process has been successfully solved. Simulation results
      indicated that the proposed method achieved decent results and would have
      practical value for the future applications.

PMID- 23865333
TI  - [Study on preparation and property of a new adsorbent for endotoxin removal in
      blood purification].
AB  - In order to remove the endotoxin from the blood of endotoxemia patients, we
      prepared a new adsorbent with heparin space arm and polymyxin B (PMB) ligand. The
      carrier of chloromethyl polystyrene resin was activated and heparin space arm was
      grafted, and then PMB ligand was immobilized onto adsorbent with glutaraldehyde.
      We employed in vitro FITC-lipopolysaccharide (FITC-LPS) static adsorption to
      characterize the adsorption properties on the adsorbent, and conducted in vitro
      lipopolysaccharide (LPS) static adsorption to measure quantitavely the adsorption
      capacity and rate, and then evaluated the blood compatibility. The in vitro
      static adsorption indicated that the adsorbent had the removal rate of LPS above
      70% with the adsorption equilibrium time for 2 hours. Blood compatibility
      experiment showed that the adsorbent had little negative effects on blood cells
      and plasma protein, and their adsorption rates were less than 10% for hemocytes
      and 20% for plasma protein respectively. This adsorbent exhibited high
      selectivity, high adsorption capacity and good biocompatibility, and presented a
      promising clinical application in the treatment of endotoxemia.

PMID- 23865334
TI  - [Construction and identification of lentiviral vector carrying FOLR1 gene].
AB  - Through this research a lentiviral vector expressing the gene of folate-binding
      protein-1 (FOLR1) was constructed and the corrsponding expression products were
      identified. Firstly, full-length of the FORL1 gene was amplified by PCR and
      cloned into the plasmid pWPI. Then it was further confirmed by PCR and
      sequencing. Secondly, after the recombinant pWPI and its helper plasmid co
      transfected the virus packaging 293T cells, SKOV3 cells were infected with the
      virus particles and sorted by flow cytometry. Thirdly, the FOLR1 gene was
      detected by RT-PCR and its protein expression was detected by Western blot.
      Finally, the recombinant expression vector was successfully constructed, and
      lentiviruses were successfully packaged by the 293T cells. A great quantity of
      green fluorescent cells could be seen after the SKOV3 cells were effectively
      infected with the lentiviruses carrying the FOLR1 gene. The sorting could be done
      and detected by cytometrying the FORL1 gene and its stable expression by the two
      methods above, which laid experimental foundation for exploring its biological
      function in ovarian cancers.

PMID- 23865335
TI  - [Determination of oxaprozin in human plasma with high performance liquid
      chromatography (HPLC) and its application].
AB  - The present research was aimed to develop a high performance liquid
      chromatography (HPLC) method to determine oxaprozin in plasma and to evaluate the
      bioavailability of two oxaprozin enteric coated tablets. A C18 column was used to
      separate the plasma after protein precipitation and the mobile phase was methanol
      12. 5mmol/L ammonium acetate buffer solution (pH=3.0)(71:29). The calibration
      curve was linear in the concentration range of 0. 50-70. 56 microg . mL-1, and
      the intra and inter-day RSDs were less than 12. 33% and 10. 42% respectively. A
      single dose of 0. 4 g reference preparation or test preparation of oxaprozin
      enteric coated tablets was administered to 20 healthy volunteers according to a
      randomized crossover study. AUC0-->264h were (4 917. 44 +/- 629. 57) microg . h .
      mL-1 and (4 604. 30+/-737. 83) microg . h . mL-1, respectively; Cmax were (52.
      34+/-7. 68) microg . mL-1 and (48. 66+/-4. 87) microg . mL-1, respectively; Tmax
      were (18. 70+/-2.27) h and (19. 30+/-1. 63) h, respectively; The relative
      bioavailability of test preparation was 94.0% +/- 13. 7%. The method is simple,
      rapid and selective for oxaprozin determination. There is no significant
      difference in the main pharmacokinetic parameters between the test formulation
      and reference formulation and the two formulations are in bioequivalence.

PMID- 23865336
TI  - [Research progress of methods for brain vigilance improvement].
AB  - Vigilance is defined as the ability to maintain attention or alertness over
      prolonged periods of time. Since Mid-20th century, following the increasing man
      machine communication, high level of vigilance has been demanded in many areas
      including driving safety, medical care and therapy, aerospace and military
      affairs, etc. Therefore, finding quick methods to improve the level of vigilance
      has become a key issue in medical study. Based on physical regulation, chemical
      regulation and physiological regulation, the research progress has been
      summarized in this paper. We, furthermore, also try to predict the future trend
      in this academic area and develop some tentative ideas about seeking more
      effective and convenient ways to improve the level of brain vigilance.

PMID- 23865337
TI  - [Potential applications of beta-elemene in anti-atherosclerosis and anti
      restenosis].
AB  - It is well known that beta-elemene is a broadly effective antitumor drug. In
      recent years, many studies suggested that beta-elemene also has potential value
      in the treatment of atherosclerosis and restenosis. In this paper, the effect of
      beta-elemene in inhibition of angiogenesis, inhibition of thrombus formation,
      improvement of hemorheology, protection against oxidative injuries, anti
      inflammation and suppression of restenosis after percutaneous transluminal
      coronary angioplasty (PTCA) are summarized and reviewed.

PMID- 23865338
TI  - [Research progress of external tufted cells in olfactory glomerulus].
AB  - External tufted (ET) cells are the major excitatory elements coordinating the
      activities of glomerulars and mediating the input from the olfactory neurons to
      mitral cells. The ET cells participate in inter-and intra-glomerular
      microcircuits in the olfactory bulb, link the isofunctional odor columns within
      the same olfactory bulb, and play an important role in olfactory information
      processing. This paper reviews the research progress of the anatomy and
      physiological properties and electrophysiological modeling of ET cells, elaborate
      the problems and defects in the field. And then it further gives some proposals
      for the future research of electrophysiological properties, development of
      olfactory information coding and performance of modeling of ET cells.

PMID- 23865339
TI  - [Advancement of studies on second mitochondrial activator of caspase].
AB  - Smac is a mitochondrial protein that interacts with inhibitor of apoptosis
      proteins (IAPs). Upon apoptotic stimuli, the Smac is released into the cytoplasm
      to inhibit the capase-binding activity of IAPs. The low expression of Smac in
      tissues has been reported existing in various cancers. Smac plays key roles in
      prognosis and chemoradiotherapy resistance of malignant tumor besides neoplasm
      genesis and growth. Furthermore, Smac may be a molecular therapeutic target in
      cancer patients. Overexpression of Smac by transfecting extrinsic Smac gene or
      Smac mimetic into tumor cell can improve their sensitivity to radiotherapy and
      chemotherapy, which has great significance to the treatment of tumor. Our review
      will focus on the roles of Smac in structure, pro-apoptotic mechanism, tissue
      distribution and cancer treatment.

PMID- 23865340
TI  - [Flexible print circuit technology application in biomedical engineering].
AB  - Flexible print circuit (FPC) technology has been widely applied in variety of
      electric circuits with high precision due to its advantages, such as low-cost,
      high specific fabrication ability, and good flexibility, etc. Recently, this
      technology has also been used in biomedical engineering, especially in the
      development of microfluidic chip and microelectrode array. The high specific
      fabrication can help making microelectrode and other micro-structure equipment.
      And good flexibility allows the micro devices based on FPC technique to be easily
      packaged with other parts. In addition, it also reduces the damage of
      microelectrodes to the tissue. In this paper, the application of FPC technology
      in biomedical engineering is introduced. Moreover, the important parameters of
      FPC technique and the development trend of prosperous applications is also
      discussed.

PMID- 23865341
TI  - [Research progresses in cancer stem cell and its vascular microenvironment].
AB  - Cancer stem cells (CSCs) and angiogenesis play important roles in generation and
      development of malignant tumours. The number of researches concerned both of them
      is increasing rapidly and many impressive conclusions have been achieved based on
      recent studies. It is indicated that the CSCs have complicated interaction with
      the adjacent vascular microenvironment and they act on the disease progression
      together. CSCs may enhance angiogenesis while the vascular microenvironment has
      effects on maintenance and even induction of stemness, and new illustrations of
      mechanisms are constantly obtained. In this review, we summarize the current
      research status of mutual actions between CSCs and the vascular microenvironment,
      and also overview the latest progresses about relevant targeted therapies, to
      provide advisable information for future preclinical and clinical explorations.

PMID- 23865342
TI  - Interventions to reduce platelet prophylactic transfusions in patients with
      hypoproliferative thrombocytopenia: providing patients with the full benefit.
AB  - To reduce the infectious and immunologic complications of platelet transfusions
      in patients with hypoproliferative thrombocytopenia, three interventions have
      aimed to decrease the number of prophylactic platelet transfusions received by
      such patients for the prevention of bleeding. These are the reduction of the
      platelet count threshold triggering prophylactic transfusion, the administration
      of low-dose (as opposed to standard-dose) platelet transfusions, and the
      administration of therapeutic (as opposed to prophylactic) platelet transfusions.
      We demonstrate that--in terms of absolute risk reduction in all infectious and
      some immunologic complications of transfusion--patients can benefit more from the
      transition to all-apheresis platelet supply than from the reduction of the
      platelet count threshold from 20,000/microL to 10,000/microL (mean reduction in
      the number of donor exposures by 26.28 versus 9.6, respectively). Also, patients
      can benefit just as much from the transition to an all-apheresis platelet supply
      as from the transition to a new standard of care employing therapeutic platelet
      transfusions for selected patients with hypoproliferative thrombocytopenia (mean
      reduction in the number of donor exposures by 4.08 versus 3.24, respectively).
      Finally, policies of low-dose platelet transfusions can directly benefit patients
      with hypoproliferative thrombocytopenia, effecting a median reduction in the
      number of donor exposures by 12.5 compared with a setting transfusing platelet
      pools, only if they are combined with Patient Blood Management (PBM) and an all
      apheresis platelet supply. Thus, whatever strategy is adopted from among these
      three interventions, the replacement of the current platelet pools with an all
      apheresis platelet supply is necessary for providing patients with the full
      benefit.

PMID- 23865343
TI  - Application of proteomics in lab diagnosis.
AB  - Proteomics is defined as a large-scale study of proteins, in particular their
      functions and structures. This review was aimed to introduce the application of
      proteomics in lab diagnosis. Beforehand, we introduce the methods, which were
      used in proteomics also the advantages and disadvantages of proteomics are
      challenged. In the end, the necessity of proteomics for understanding the
      structure, function, and interaction of proteins in different fields of sciences
      including biomarkers, drug discovery, etc. will be discussed.

PMID- 23865344
TI  - Diagnosis of essential hypertension in humans by the determination of plasma
      renal cortexin using enzyme-linked immunosorbent assay.
AB  - BACKGROUND: More than 90% of all hypertensive persons are reported to have
      essential hypertension (EH), a particular form of elevated blood pressure, for
      which no diagnostic test is currently available. The level of plasma renal (R)
      cortexin (PRC), a hypotensive protein produced in the kidney cortex cells, was
      reported to be reduced from 218 nM in the plasma of normotensive persons (NP) to
      0 nM in the plasma of patients with EH. The feasibility of using the
      determination of PRC by enzyme-linked immunosorbent assay (ELISA) as a diagnostic
      test for EH was investigated. METHODS: The PRC was determined by ELISA using
      electrophoretically pure cortexin as the antigen. A total of 344 persons (male
      and female) with EH, with or without diabetes mellitus (DM), and receiving or not
      receiving any anti-hypertensive and/or anti-diabetic medication at presentation,
      as well as an equal number of age- and gender-matched NP participated in the
      study. RESULTS: All persons with EH, with or without co-existing DM, were found
      to have 0 nM PRC, regardless of whether they were receiving anti-hypertensive and
      anti-diabetic drugs, including those who had been taking these medications over
      an extended period of time (3 months). CONCLUSIONS: The determination of PRC as a
      marker protein by ELISA, a rapid method that can be carried out in any diagnostic
      laboratory, was shown to be suitable for the diagnosis of EH, even in those
      subjects who had co-existing DM and were receiving both anti-hypertensive and
      anti-diabetic medication.

PMID- 23865345
TI  - The evaluation of the FOXO1, KLF9 and YT521 genes expression in human endometrial
      cancer.
AB  - BACKGROUND: The current study was designed to explore the changes of the mRNA
      levels of the YT521, Forkhead box protein O1 (FOXO1), and Kruppel-like factor 9
      (KLF9) proteins in human normal and cancerous endometrial tissue. METHODS: The
      study was conducted in 30 premenopausal patients diagnosed with endometrial
      cancer and 20 premenopausal women with no clinically documented abnormalities of
      the endometrium undergoing hysterectomy. Gene expression levels were assayed
      using quantitative real-time PCR. RESULTS: The endometrial tissue FOXO1 mRNA
      level (0.82 +/- 0.27) of patients with endometrial cancer was significantly lower
      (p < 0.001) than controls (4.51 +/- 2.68). In subjects with endometrial cancer
      the KLF9 mRNA level (1.12 +/- 0.38) was lower (p < 0.001) when compared to
      controls (3.11 +/- 1.52). A remarkable (not significant, p = 0.069) increase was
      found in the YT521 mRNA level of patients' endometrial tissue (11.19 +/- 3.99) in
      comparison with the control subjects (8.82 +/- 5.01). No significant difference
      was detected for the FOXO1, KLF9 and YT521 mRNA levels of the endometrial tissue
      of patients with cancer at different stages. CONCLUSIONS: It is suggested that
      the alteration of the gene expression profiles of FOXO1, KLF9 and YT521, which
      occur in human endometrial cancers likely play a crucial role in initiation of
      cancer.

PMID- 23865346
TI  - Glycohemoglobin levels with severity of periodontitis in non-diabetic population.
AB  - BACKGROUND: Periodontal disease is closely related to type 2 diabetes and is an
      important complication of diabetes. There are few studies about the relationship
      the glycohemoglobin levels with severity of periodontitis in non-diabetic
      population. We therefore planned this study to evaluate the glycohemoglobin
      levels with severity of periodontitis in non-diabetic population. METHODS: This
      study was conducted on 50 age and gender matched subjects in each of the three
      groups (according to the grades of mobility in periodontitis), a total of 150 non
      diabetic periodontitis patients (Grade 1, Grade 2, and Grade 3 mobility) and 50
      non-diabetic periodontitis patients with Grade 0 mobility (controls), in
      collaboration with the Department of Periodontics of Dental College and
      Department of Biochemistry, PGIMS, Rohtak, Haryana. After obtaining informed
      consent, fasting venous blood samples of all the non-diabetic periodontitis
      patients of all grades were collected aseptically for HbA1c, plasma glucose, and
      serum C-reactive protein (CRP) estimation. RESULTS: A total of 150 non-diabetic
      periodontitis patients (Grade 1, Grade 2, and Grade 3 mobility) and 50 age and
      gender matched controls participated in the study. There was no significant
      difference in fasting plasma glucose and postprandial plasma glucose in non
      diabetic periodontitis patients with Grade 1, Grade 2, and Grade 3 mobility as
      compared to controls, non-diabetic periodontitis patients with Grade 1 mobility
      as compared to Grade 2, non-diabetic periodontitis patients with Grade 1 mobility
      as compared to Grade 3 and non-diabetic periodontitis patients with Grade 2
      mobility as compared to Grade 3. Glycohemoglobin and serum C-reactive protein
      levels were significantly increased in non-diabetic periodontitis patients with
      Grade 1, Grade 2, and Grade 3 mobility as compared to controls, non-diabetic
      periodontitis patients with Grade 1 mobility as compared to Grade 3 and non
      diabetic periodontitis patients with Grade 2 mobility as compared to Grade 3. The
      difference of serum C-reactive protein levels were significant. However,
      glycohemoglobin levels were non-significant between non-diabetic periodontitis
      patients with Grade 1 and Grade 2 mobility. CONCLUSIONS: The evidence of
      association between periodontitis and increased glycohemoglobin increases
      attention to the diagnosis and treatment of periodontitis, consequently improving
      the patient's oral health and prevention of occurrence in future diabetes. An
      understanding of these correlations is important to allow dental health care
      providers to inform patients with periodontitis of their increased risks and to
      counsel such patients to seek additional medical assessment or intervention as
      indicated.

PMID- 23865347
TI  - The regulatory impacts of Morus Alba leaf extract on some enzymes involved in
      glucose metabolism pathways in diabetic rat liver.
AB  - BACKGROUND: Many traditional therapies have been proposed as alternative regimens
      for treatment of diabetes mellitus. The Morus Alba (MA) leaf is a natural
      therapeutic compound which is shown to have antidiabetic properties. The aim of
      the present study was to determine whether MA leaf extract is capable of
      regulating liver enzymes that are involved in glucose metabolism pathways in
      normal and Streptozotocin (STZ)-induced diabetic rats. METHODS: Forty healthy
      adult male Wistar rats (eight weeks old) weighing about 250 +/- 10 g were taken
      for this experiment. The rats were divided into 4 groups with 10 rats in each
      group and treated through a gavage tube for a period of two months as follows:
      group I: non diabetic control rats with distilled water; group II: non diabetic
      rats with 1.0 g/kg per day; group III: diabetic control rats with distilled water
      and group IV: diabetic rats with MA 1.0 g/kg per day. At the end of the 8th week,
      serum glucose, insulin and hepatic glucokinase activity were measured using
      standard methods and compared between diabetic and healthy rats. We also assessed
      the expression of phosphofructokinase-1 enzyme at the level of mRNA, using a Real
      Time-PCR method. RESULTS: Findings of the present study demonstrated that MA leaf
      extract can significantly increase liver glucokinase activity and serum insulin
      levels in diabetic rats (p < 0.05). It also significantly attenuated the serum
      glucose level in rats compared to the control groups (p < 0.05). Also, the body
      weight of diabetic rats was significantly (p < 0.05) decreased as compared to
      their initial weight. However, the body weights of diabetic rats treated with MA
      increased in the same way as normal control rats. CONCLUSIONS: The present
      findings suggest that the antihyperglycemic action of MA is mediated by
      increasing liver glucokinase activity and serum insulin level. These results are
      additional, definite evidence supporting MA as traditional medicine for diabetic
      patients.

PMID- 23865348
TI  - Reference values of serum rheumatoid factor in coastal residents.
AB  - BACKGROUND: This study aims to investigate the reference values of serum
      rheumatoid factor (RF) in coastal residents. METHODS: We collected 1,762 serum
      samples from 20 - 69 year-old males who participated in the population-based
      Fangchenggang Area Male Health and Examination Survey from September 2009 to
      December 2009. The values of serum RF were measured by immunoturbidimetry.
      RESULTS: The established normal reference value range of serum RF (< or = 18.90
      IU/mL) in healthy adult males who live in coastal areas is lower than the current
      value that is extensively used (20 IU/mL). Age, ethnicity, and smoking specific
      reference values were calculated. Differences were found within groups, but no
      significant difference in drinking was observed. CONCLUSIONS: It is suggested
      that every special region should establish respective normal reference values of
      serum RF in healthy individuals.

PMID- 23865349
TI  - Effect of picric acid and enzymatic creatinine on the efficiency of the
      glomerular filtration rate predicator formula.
AB  - BACKGROUND: To investigate the impact of serum creatinine measurement on the
      applicability of glomerular filtration rate (GFR) evaluation equations. METHODS:
      99mTc-DTPA plasma clearance rate was used as GFR reference (rGFR) in patients
      with chronic kidney disease (CKD). Serum creatinine was measureded using
      enzymatic or picric acid creatinine reagent. The GFR of the patients were
      estimated using the Cockcroft-Gault equation corrected for body surface area,
      simplified Modification of Diet in Renal Disease (MDRD) equation, simplified MDRD
      equation corrected to isotopes dilution mass spectrometry, the CKD epidemiology
      collaborative research equation, and two Chinese simplified MDRD equations.
      RESULTS: Significant differences in the eGFR results estimated through enzymatic
      and picric acid methods were observed for the same evaluation equation. The
      intraclass correlation coefficient (ICC) of eGFR when the creatinine was measured
      by the picric acid method was significantly lower than that of the enzymatic
      method. The assessment accuracy of every equation using the enzymatic method to
      measure creatinine was significantly higher than that measured by the picric acid
      method when rGFR was > or = 60 mL/min/1.73m2. CONCLUSIONS: A significant
      difference was demonstrated in the same GFR evaluation equation using the picric
      acid and enzymatic methods. The enzymatic creatinine method was better than the
      picric acid method.

PMID- 23865350
TI  - Evaluation of a new recombinant antigen-based Virotech Treponema pallidum screen
      ELISA for diagnosis of syphilis.
AB  - BACKGROUND: The purpose of this study was to evaluate the diagnostic performance
      of the new Sekisui Virotech Treponema pallidum Screen ELISA in comparison with
      the currently used treponemal tests, TPPA and FTA-abs, and to compare this new
      ELISA to the FDA approved Phoenix Trep-Sure ELISA. METHODS: To establish the
      sensitivity and specificity of the Virotech Screen, 421 serum samples from
      different panels of infected and noninfected patients, sera from seronegative
      pregnant women as well as international syphilis standard sera and panels were
      tested. RESULTS: In comparison to combined TPPA/FTA-abs, Phoenix Trep-Sure and
      Virotech Screen demonstrated a sensitivity of 100% and a specificity of 93.9% and
      98.3%, respectively. All samples of a well defined syphilis serum panel were
      correctly identified by the Virotech test, whereas the Phoenix test identified
      two Treponema negative samples as equivocal. Results of both ELISAs highly
      correlated with TPPA negative and positive samples. The analytical sensitivity of
      the Virotech Screen with international standards 05/122 and 05/132 was determined
      at 0.02 IU/mL and 0.03 IU/mL, respectively, and was slightly superior to the
      Phoenix Trep-Sure. CONCLUSIONS: The Virotech Screen ELISA demonstrated good
      diagnostic sensitivity and specificity when evaluated as a screening test for
      syphilis among various patient populations, including samples with increased
      rates of false-positive nontreponemal test results. Thus, the new Virotech ELISA
      may be used in automatic analysers as an alternative to the manual TPPA. However,
      the use of a confirmatory test remains a must in order to avoid false-positive
      results.

PMID- 23865351
TI  - Increased circulating levels of CXC chemokines is correlated with duration and
      complications of the disease in type-1 diabetes: a study on Iranian diabetic
      patients.
AB  - BACKGROUND: Type-1 diabetes (T1D) is characterized as a heterogenous autoimmune
      disease. Immune system factors are important in the pathogenesis of T1D.
      Chemokines as crucial members of the immune system are key factors in the
      pathogenesis of several autoimmune diseases, including T1D. They are potent
      chemotactic cytokines with various functions varied from maturation, trafficking
      of leukocytes, to angiogenesis, angiostasis, and homing of stem cells. Therefore,
      the current study was aimed to examine if the expression of pro-angiogenic CXC
      chemokines like CXCL1 and anti-angiogenic chemochines such as CXCL9 are
      associated with duration and complications of T1D in Iranian diabetic patients.
      METHODS: In this experimental study, blood samples were collected from 209 T1D
      patients and 189 healthy controls. The serum levels of CXCL1 and CXCL9 were
      measured by ELISA. Demographic data were also collected on a questionnaire which
      was designed specifically for this study. RESULTS: Increased plasma levels of
      chemokines studied (CXCL1 and CXCL9) were observed in T1D patients compared to
      controls. Current findings also demonstrated that there was a close association
      between chemokines and complications of T1D and chemokines were elevated in T1D
      patients suffering complications. CONCLUSIONS: Our results probably suggest that
      the serum levels of CXCL1 and CXCL9 play important roles in T1D pathogenesis. It
      is also worth noting that these factors are useful prognostic and/or diagnostic
      biological markers in T1D patients.

PMID- 23865352
TI  - Evaluation of calcium, magnesium, potassium and sodium in biological samples of
      male human immunodeficiency virus patients with tuberculosis and diarrhea
      compared to healthy control subjects in Pakistan.
AB  - BACKGROUND: Electrolyte deficiency has been associated with an increased risk of
      human immunodeficiency virus type 1 (HIV-1) disease progression and mortality.
      This study examined the association between low electrolyte concentrations in
      blood and scalp hair and the presence of opportunistic infections in patients
      with acquired immune deficiency syndrome (AIDS). METHODS: Sixty-two male HIV
      positive patients (HIV-1) from various cities in Pakistan were recruited to the
      study. These Patients were divided into two groups according to secondary
      infections (tuberculosis and high fever with diarrhea), and biological samples
      (scalp hair, serum, blood and urine) were collected from them. As a comparative
      control group, 120 healthy subjects (males) of the same age group (31 - 45
      years), socio-economic status, localities and dietary habits were also included
      in the study. The elements in the biological samples were analyzed by flame
      atomic absorption spectrophotometry after microwave-assisted acid digestion.
      Validity and accuracy of the methodology were checked using certified reference
      materials (CRMs) and against values obtained by a conventional wet acid digestion
      method on the same CRMs. RESULTS: The results indicated significantly lower
      levels of calcium, potassium, magnesium and natrium in all analyzed biological
      samples (blood, serum and scalp hair) of male patients with Acquired Immune
      Deficiency Syndrome (AIDS) in comparison to healthy controls (p < 0.01), while
      the levels of these elements were found to be higher in urine samples of the AIDS
      patients than in those of the control group. CONCLUSIONS: These data offer
      guidance to clinicians and other professionals investigating the deficiency of
      electrolytes in biological samples (scalp hair, serum and blood) of AIDS patients
      in relation to healthy subjects.

PMID- 23865353
TI  - The clinical value of new tumor biomarker cytokeratin 2G2 detection in non-small
      cell lung cancer patients.
AB  - BACKGROUND: Many tumor markers are analyzed for usefulness in diagnosis,
      prognosis, and monitoring. The purpose of this study was to evaluate a new type
      of tumor biomarker, cytokeratin (CK)-2G2, in serum for the early diagnosis,
      confirmative diagnosis as well as assessment of treatments of non-small cell lung
      cancer (NSCLC). METHODS: Use a chemiluminescent method to examine the serum CK
      2G2 levels in 100 patients with non-malignant lung diseases and 100 cases from
      the healthy population, as well as 124 cases of NSCLC patients prior to
      chemotherapy, after one course of treatment and after two courses of treatment.
      RESULTS: The average levels of CK-2G2 in the serum of NSCLC patients was found to
      be significantly higher than that of the group of non-malignant patients as well
      as the healthy control group (p < 0.01). It was further observed that CK-2G2 is
      markedly higher in squamous-cell carcinoma than in adenocarcinoma (p < 0.05)
      whereas CK-2G2 was found to be higher in stages III and IV than stages I and II
      (p < 0.05) and CK-2G2 is markedly higher in large tumor size (> 3cm) than in
      small tumor size (< or = 3cm) (p < 0.05). Serum CK-2G2 levels for patients with
      cancer progression were found to increase after two courses of chemotherapy (p <
      0.01) whereas patients with stabilized tumorigenesis or tumor regression showed a
      significant trend of CK-2G2 decrease (p < 0.01). CONCLUSIONS: Detection of the
      new tumor biomarker CK-2G2 has certain clinical values for early diagnosis,
      verification of diagnosis as well as classification of patients. Thus it is
      warranted that CK-2G2 be widely deployed as a new type of cost effective
      parameter for evaluating efficacy of chemotherapy of NSCLC.

PMID- 23865354
TI  - The effects of acute and regular exercise on calcium, phosphorus and trace
      elements in young amateur boxers.
AB  - BACKGROUND: The aim of this study was to assess the acute and chronic effects of
      vigorous physical activity, with and without zinc supplementation, on
      distribution of elements in young amateur boxers. METHODS: The 8 week
      intervention trial experiment was designed with 32 healthy adolescent males in
      three parts: part 1, a 1 hour boxing training program; part 2, 4 weeks of regular
      boxing training without any supplementation; part 3, 4 weeks of regular boxing
      training with supplementation of pills containing 50 mg oral zinc. Plasma
      calcium, phosphorus, zinc, iron, copper, and magnesium levels of all participants
      were measured before and after each part of the study. RESULTS: After acute
      exercise serum calcium, zinc, copper levels decreased (p < 0.001; 0.001 and
      0.017, respectively) and phosphorus increased (p < 0.001); iron and magnesium
      levels did not differ (p > 0.05). However, after 4 weeks of regular boxing
      training there was a decrease in zinc (93.92 +/- 9.03 microg/dL vs. 85.86 +/-
      10.32 microg/dL, p < 0.001) and an increase in calcium concentrations (9.62 +/-
      0.34 microg/dL vs. 9.90 +/- 0.26 microg/dL, p < 0.001). Zinc supplementation
      increased plasma calcium, phosphorus, and iron and decreased copper and magnesium
      (p < 0.001). CONCLUSIONS: The body element distribution of children in pubertal
      age changes with physical activities. Zinc supplementation can negatively affect
      their magnesium and copper concentrations.

PMID- 23865355
TI  - Association of the apolipoprotein E variants with susceptibility to pregnancy
      with preeclampsia.
AB  - BACKGROUND: Apolipoprotein E (ApoE) polymorphism plays a significant role in the
      development of several diseases, but its role in the preeclampsia disease
      incidence is not clear. Therefore, the purpose of this study was to investigate
      the susceptibility of some pregnant women to preeclampsia. METHODS: In a
      comparative cross-sectional study, the ApoE polymorphism genotypes were
      investigated in 100 patients with preeclampcia and 100 normal pregnant, using the
      polymerase chain reactions (PCR) analysis. Serum lipids and lipoproteins
      concentrations were also evaluated using the commercially available kits.
      RESULTS: The difference in distribution of the epsilon2/epsilon2,
      epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon3, epsilon3/epsilon4 and
      epsilon4/epsilon4 genotypes between patient subjects and controls was not
      significantly (p = 0.266). The data obtained for Apo epsilon4, epsilon2 and
      epsilon3 alleles in the patient group was not different significantly from those
      obtained for the control group (p = 0.220). The VLDL and TG levels of the patient
      group were higher significantly than controls (p < 0.01, p < 0.01 respectively).
      The data obtained for HDL concentration (52.2 +/- 16.1 g/dL) of the patient group
      was not different significantly from controls (49.4 +/- 12.5 g/dL). The
      difference between LDL concentration of patients with preeclampsia and controls
      was not significant. The cholesterol concentration of control subjects was not
      different significantly from patient subjects. CONCLUSIONS: The observed profiles
      of ApoE alleles and genotypes frequencies suggest that Apo E polymorphism does
      not play a major role in the development of preeclampsia. Nonetheless, the
      abnormal lipid profiles that we found in patients with preeclampsia may have a
      genetic explanation and/or contribution.

PMID- 23865356
TI  - Adenosine receptor expression and gene reference evaluation in human leukocytes.
AB  - BACKGROUND: Peripheral blood mononuclear cells and isolated polymorphonuclear
      neutrophilis were used to evaluate gene expression studies. Unfortunately, there
      are many methodological problems related to these cellular models, limiting their
      use. The aim was to evaluate a fast and easy procedure for the extraction of
      total RNA from leukocytes obtained from human whole blood (WB) < 10 mL; to
      determine adenosine receptor (AR) mRNA expression in WB samples of normal
      subjects and to establish the most stable reference genes for data normalization.
      METHODS: mRNA expression was performed by Real-Time PCR. RESULTS: The most stably
      expressed genes were TPT1, EEF1A, and RPL13A. Similar levels of mRNA expression
      were observed for A2aR, A2bR, and A3R while lower levels were measured for A1R (p
      = 0.02 A1R vs. A2aR; p = 0.04 A1R vs. A3R). CONCLUSIONS: Our study represents an
      important and useful starting point for future investigations devoted to evaluate
      the expression of ARs in human diseases.

PMID- 23865357
TI  - Investigation of the effects of Chlorella vulgaris supplementation on the
      modulation of oxidative stress in apparently healthy smokers.
AB  - BACKGROUND: Smoking is among the established yet modifiable risk factors for
      cancers, cardiovascular diseases, and pulmonary disorders. Oxidative stress has
      been proposed as a key mechanism mediating the deleterious consequences of
      smoking. The present study evaluated the effect of supplementation with Chlorella
      vulgaris, a nutrient and bioactive green microalgae with proven antioxidant
      capacity, on the burden of oxidative stress in Iranian smokers. METHODS: Thirty
      eight smokers (mean age: 37.11 +/- 1.69 years; females: 18.4%) were administered
      C. vulgaris extract (3600 mg/day) for a period of 6 weeks. Fasted serum samples
      collected at baseline and after the completion of study were analyzed for the
      concentrations of vitamin C, vitamin E, glutathione, and malonedialdehyde (MDA)
      as well as activities of superoxide dismutase, glutathione peroxidase, and
      catalase. Total antioxidant capacity of serum was also determined by the ability
      of serum to inhibit the formation of ferryl myoglobin radical species. RESULTS:
      Six-week supplementation with C. vulgaris extract in smokers was associated with
      marked elevation of all assessed serum antioxidant measures (p < 0.001) and
      significant reduction of MDA levels (p = 0.002). After gender segregation, a
      similar pattern of changes was observed for both male and female subjects apart
      from lack of significant change in serum vitamin E status in females. Although
      the magnitude of change in serum vitamin E was significantly greater in males
      compared to females (p = 0.014), there was no significant change in the magnitude
      of changes for other assessed parameters between the genders. CONCLUSIONS:
      Supplementation with C. vulgaris extract significantly improves antioxidant
      status and attenuates lipid peroxidation in chronic cigarette smokers. Hence, C.
      vulgaris might prevent the disease burden and mortality rate associated with
      smoking.

PMID- 23865358
TI  - The effect of intermedin on angiotensin II and endothelin-1 induced ventricular
      myocyte hypertrophy in neonatal rat.
AB  - BACKGROUND: Intermedin (IMD), a novel peptide related to calcitonin gene-related
      peptide (CGRP) and adrenomedullin (ADM), may have localized actions as a
      modulator of cardiac function. The aim of the study is to explore the effect of
      IMD on angiotensin II (Ang II) and endothelin-1 (ET-1) induced hypertrophy in
      ventricular myocytes of neonatal rat and to try to elucidate the possible
      mechanism. METHODS: Neonatal rat cardiomyocytes were cultured in serum-free
      medium with and without AngII (1 micromol/L) or ET-1 (60 micromol/L) in the
      presence and absence of IMD (1 micromol/L). Hypertrophic responses (including
      cell surface area, alpha-actin, and beta-myosin heavy chain mRNA expression) and
      cardiomyocyte expression of NADPH oxidase gp91phox were determined. RESULTS: Ang
      II induced increases in cardiomyocyte size to 305 +/- 32 microm2 (n = 198, p <
      0.05, at 48 hours), alpha-actin expression to 4 +/- 2.8-fold (n = 6, p < 0.05, at
      48 hours) and beta-myosin heavy chain expression to 11 +/- 4.8-fold (n = 6, p <
      0.05, at 48 hours), and expression of the gp91phox subunit of NADPH oxidase to
      29.4 +/- 12.7-fold (n = 6, p < 0.05, at 48 hours). These effects were all
      significantly inhibited by IMD; cardiomyocyte size, alpha-actin expression, beta
      myosin heavy chain expression, and gp91phox expression were reduced to 265 +/- 32
      microm2 (n = 374, p < 0.05), 3.0 +/- 1.7-fold (n = 6, p < 0.05), 8.7 +/- 4.9-fold
      (n = 6, p < 0.05), 3.9 +/- 3-fold (n = 6, p < 0.05), respectively. IMD also
      significantly inhibited ET1-induced increases in cardiomyocyte size and
      superoxide generation. CONCLUSIONS: IMD exerts an antihypertrophic effect on
      neonatal cardiomyocytes by reduced levels of superoxide, suggesting that an
      antioxidant action contributes to the antihypertrophic actions of IMD.

PMID- 23865359
TI  - Decreased paraoxonase 1, arylesterase enzyme activity, and enhanced oxidative
      stress in patients with mitral and aortic valve insufficiency.
AB  - BACKGROUND: Oxidative stress is reportedly associated with several cardiovascular
      diseases. The antioxidant ability of high density lipoprotein (HDL) is, at least
      in part, attributable to the pleiotropic serum paraoxonase (PON1). The aim of the
      study was to investigate the body oxidant/antioxidant balance in patients with
      mitral regurgitation (MR) and aortic regurgitation (AR) to get new points of view
      for the underlying oxidative mechanisms. METHODS: Oxidative stress index (OSI),
      total oxidant status (TOS), and total antioxidant status (TAS) were examined in
      addition to the PON1 and arylesterase (ARE) enzyme activities in fifty-six
      patients and thirty-seven healthy control subjects. RESULTS: Serum PON1 and ARE
      enzyme activities were statistically significantly reduced in heart valve disease
      (HVD) patients (p = 0.0005 and p < 0.0001, respectively), whereas TOS and OSI
      levels were found to be significantly higher (p = 0.0021 and p < 0.0001,
      respectively). CONCLUSIONS: Serum PON1 activity is reduced in patients with HVD,
      caused by elevated oxidative stress and disturbances of heart valve metabolism.
      The findings from this novel detailed approach, implicate an
      inflammatory/oxidative stress process in the pathogenesis of the valve's
      presentation associated with the HVD. The strength of the significance in
      differences encourage us to propose that the role of oxidative stress in HVD
      pathogenesis is very prominent, and oxidative stress markers are potential
      ancillary tests to evaluate the state of the disease.

PMID- 23865360
TI  - Clinical parameters and aMMP-8-concentrations in gingival crevicular fluid in
      pregnancy gingivitis.
AB  - BACKGROUND: During pregnancy hormonal changes may increase the risk for
      developing gingivitis. The aim of this study was to evaluate the signs of
      gingival inflammation and the enzyme activity of matrix metalloproteinase-8 (aMMP
      8) in the gingival crevicular fluid of pregnant women. METHODS: After approval by
      the ethics commission, a total of 40 volunteers participated in the study; group
      1 (n = 20, age: 32 +/- 4 years) with pregnant women, and group 2 (n = 20, age: 30
      +/- 10 years) with age-matched non-pregnant women as controls. After obtaining
      anamnestic data, the dental examination included assessment of oral hygiene,
      gingival inflammation, probing pocket depth, and recession. Gingival crevicular
      fluid was collected from both groups. A quantitative determination of aMMP-8
      concentrations in the gingival crevicular fluid samples was performed. RESULTS:
      The aMMP-8 values of group 1 were higher (median 6.25 ng/mL aMMP-8 eluate)
      compared with group 2 (median 3.88 ng/mL aMMP-8 eluate), but the difference was
      not statistically significant (p = 0.265). Group 1 showed significantly increased
      probing pocket depths (p = 0.001). Gingival inflammation was present in 80% of
      the pregnant women, but only in 40% of the control subjects. CONCLUSIONS: It was
      shown that during pregnancy changes related to periodontal health could be
      observed. Higher aMMP-8 values, elevated probing pocket depths, and an increase
      of gingival inflammation could be detected in comparison with non-pregnant women.

PMID- 23865361
TI  - KIR2DL1-HLA signaling pathway: notable inhibition in the cytotoxicity of allo-NK
      cell against KG1A cell.
AB  - BACKGROUND: KIR2DL1 is an important member of killer cell immunoglobulin-like
      receptors (KIRs). It recognizes the C2 group of alleles exclusively and delivers
      signals that inhibit NK cell cytotoxicity. METHODS: In this study, NK cells were
      isolated by magnetic activated cell sorting (MACS) from peripheral blood of 12
      healthy unrelated male donors. Flow cytometry (FCM) was used to evaluate the
      purity of NK cells and phenotypic KIR2DL1 expression on them. The lysis of KG1A
      and K562 cells by NK cells was analyzed in the lactate dehydrogenase (LDH) assay
      to investigate whether KIR2DL1 expression on NK cells would affect the
      cytotoxicity. RESULTS: Significant differences in KIR2DL1 frequency were noted
      among the donors (range, 27.14% - 92.49%). NK cells with lower KIR2DL1 expression
      exerted higher cytolytic activity against KG1A cells, whereas those with higher
      KIR2DL1 expression exerted significantly lower lysis against KG1A cells (R2 =
      0.8169, p < 0.05). CONCLUSIONS: KIR2DL1 expression frequency was negatively
      correlated with the cytotoxicity of NK cells against KG1A cells. This study
      discovered that differential KIR2DL1 expression could positively affect the lytic
      activity of NK cells against KG1A cells, suggesting potential clinical value of
      KIR2DL1 selection in the treatment of acute myeloid leukemia (AML) patients.

PMID- 23865362
TI  - Prognostic implication of BAALC gene expression in adult acute myeloid leukemia.
AB  - BACKGROUND: Recently various molecular markers and global gene expression
      profiling have been investigated to improve risk profile characterization of AML
      with normal cytogenetics. Our main objective is to investigate the prognostic
      impact of brain and acute leukemia, cytoplasmic (BAALC) expression in AML with
      normal karyotype. METHODS: BAALC expression was analysed using quantitative real
      time (QRT) PCR. RESULTS: High expression was detected in 22 of 45 patients
      (48.9%) and its expression did not correlate with the clinical parameters of
      patients. High BAALC expressers had significantly lower incidence of CR (22.7%
      vs. 73.9%; p = 0.001), higher mortality rate (72.1% vs. 39.1%; p = 0.023), showed
      significantly shorter DFS (mean 4.5 vs. 13.21 months, p < 0.001), and inferior
      overall survival (7.02 vs. 15.02 months, p < 0.001). Multivariable analysis
      confirmed high BAALC expression as an independent risk factor for DFS and OS.
      CONCLUSIONS: BAALC expression is an important prognostic factor in AML patients
      with normal karyotype and its incorporation into novel risk-adapted therapeutic
      strategies will improve the currently disappointing cure rate of this group of
      patients.

PMID- 23865363
TI  - A detailed examination of platelet function inhibition by nitric oxide in
      platelet-rich plasma and whole blood.
AB  - BACKGROUND: The question of whether novel instruments such as multiple electrode
      aggregometry (MEA) can be used for measurement of the effects of nitric oxide
      (NO) on platelets (PLTs) has not been examined. METHODS: Therefore, we compared
      the effects of NO concentrations (1, 10, and 100 microM) on the PLT aggregation
      response to ADP, arachidonic acid (AA), collagen, ristocetin, and thrombin
      receptor-activating peptide 6 (TRAP6) using light transmission aggregometry (LTA)
      and multiple electrode aggregometry (MEA) and examined the effects of NO using
      the platelet function analyzer (PFA)-100. RESULTS: The response of PLTs to ADP
      and AA was strongly inhibited by all NO concentrations in LTA and MEA. The
      inhibition of the responses to ristocetin and collagen was detectable in MEA at
      lower NO concentrations than in LTA. However, the typically increasing lag phase
      between collagen addition and the aggregation response in the presence of NO was
      more obvious in LTA. TRAP caused a reproducible early response in the presence of
      NO in LTA which was followed by rapid PLT disaggregation, whereas even 100 microM
      NO did not inhibit the response to TRAP in MEA. Finally, NO prolonged the in
      vitro bleeding time remarkably more in the PFA-100 collagen-epinephrin cartridge
      than in the collagen-ADP cartridge. CONCLUSIONS: Whole blood versus PLT rich
      plasma, citrate versus hirudin, and high versus low shear influenced the effects
      of NO. This shows that a careful selection of models and potentially a
      combination of different methods is appropriate for a differentiated evaluation
      of pharmacological or physiological mechanisms of NO-donors or of NO-inhibitors.

PMID- 23865364
TI  - Serum proteome changes following human immunodeficiency virus infection.
AB  - BACKGROUND: Quantification of viral RNA levels and CD4 cell count determinations
      are the most widely used laboratory assays employed in monitoring HIV patients.
      However, these tests are expensive, complex to perform, and require advanced
      laboratory infrastructure and highly skilled laboratory technicians. For these
      reasons, alternative ways to monitor the progression of HIV have been sought. The
      aim of this study was to compare the serum proteome of asymptomatic HIV-positive
      subjects to HIV-negative controls in order to identify novel protein changes that
      are induced in the human serum proteome following HIV infection. It is hoped that
      monitoring changes in these protein could be used as a cheaper biomarker for the
      progression of HIV infection. METHODS: Blood was collected from volunteers
      undergoing HIV testing at a primary health clinic. Samples were separated into
      HIV-positive and HIV-negative groups, and subjected to two-dimensional gel
      electrophoresis. The gels were silver-stained and analyzed to detect significant
      differences between protein spots. Significant spots were digested with trypsin
      and subjected to analysis using MALDI-TOF mass spectrometry. RESULTS: Eleven
      spots were found to be significantly different between the two groups. Nine spots
      were significantly decreased and two spots were significantly increased in the
      HIV-positive group compared to the HIV-negative group. The proteins found to be
      decreased were identified as abnormal spindle-like microcephaly-associated
      protein, type II cytoskeletal keratin, alpha-1-acid glycoprotein, haptoglobin,
      apolipoprotein A-I, zinc finger CCCH domain-containing protein 13 and haemoglobin
      beta subunit. The proteins found to be increased were identified as pre-mRNA
      splicing factor CWC25 homolog and 60S ribosomal protein L4. CONCLUSIONS:
      Significant differences were found between HIV-positive and HIV-negative samples.
      This information could be used to develop immunoassays to analyse protein changes
      as an additional method of monitoring changes in HIV infection in the clinical
      laboratory.

PMID- 23865365
TI  - Expression of putative tumor suppressor gene spleen tyrosine kinase in esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: To study the expression of Syk (spleen tyrosine kinase) gene in human
      ESCC (esophageal squamous cell carcinoma). METHODS: We used immunohistochemical
      staining to detect Syk protein expression in esophageal carcinoma tissues and RT
      PCR (semi-quantitative reverse transcription PCR), Real-time PCR (Real-time
      quantitative PCR) and western blotting technique to detect the expression of Syk
      mRNA and protein in specimens from 4 esophageal cell lines. RESULTS:
      Immunohistochemistry analyses showed that in the esophageal cancer tissues Syk
      protein was expressed inferior to the adjacent normal one, p < 0.05. Real-time
      PCR and Western blotting showed that low expression of the Syk gene was detected
      in the 4 esophageal cancer cell lines compared with positive and negative cell
      lines, p < 0.05. CONCLUSIONS: The low expression of the Syk gene may play an
      important role in tumorigenesis in esophageal cancer.

PMID- 23865367
TI  - Unexpectedly elevated cardiac troponin I level in the patient without acute
      coronary syndrome.
AB  - BACKGROUND: Since cTnI assay is leading test in diagnostic of myocardial
      infarctions, and it is used for risk assessment in patients with ACS as well as
      unstable angina pectoris, it is very important to measure its concentration
      accurately and precisely. METHODS: Here we report a case in which there was a
      significant difference in the cTnI concentrations measured by three different
      methods, which was detected in one patient's sera during preoperative evaluation
      for cardiac surgery. RESULTS: Due to variations in the results for the cTnI
      concentrations (0.62; 0.13; 0.89 microg/L), the question was raised about the
      possibility of an interference known to occur in especially rare situations. A 76
      year-old male was operated, temporal elevation and subsequent decrease in the
      concentrations of cTnI were monitored. CONCLUSIONS: It was observed that results
      obtain with different assays are not comparable.

PMID- 23865366
TI  - Mitochondrial DNA copy number and oxidative DNA damage in placental tissues from
      gestational diabetes and control pregnancies: a pilot study.
AB  - BACKGROUND: Available evidence supports the role of reactive oxygen species in
      the pathogenesis of placental insufficiency, gestational diabetes mellitus (GDM),
      and other pregnancy complications. Abnormal placental mitochondrial function
      resulting from reactive oxygen species may also be an important precedent of
      adverse perinatal outcomes. METHODS: We investigated the association of placental
      oxidative stress with placental mitochondrial DNA (mtDNA) copy number, an
      indicator of placental mitochondrial density and possible mitochondrial
      dysfunction, using samples collected from GDM cases and controls. 8-hydroxy-2'
      deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was measured in
      placentas of 19 GDM cases and 21 controls using a competitive immunoassay.
      Placental mtDNA copy number was determined using real-time quantitative PCR.
      Bivariate and multivariable linear regression procedures were used to evaluate
      associations of these two biomarkers. RESULTS: Placental DNA oxidation was
      positively associated with mtDNA copy number in both GDM and control placentas.
      After adjusting for maternal age, pre-pregnancy body mass index and gestational
      age at delivery, mtDNA copy number increased (beta = 67.0; 95% CI 27.8 - 106.2, p
      = 0.001) for every 0.1 ng/microg increase of placental 8-OHdG among GDM cases and
      controls. CONCLUSIONS: These cross sectional data suggest an association of
      placental mtDNA copy number with oxidative stress. The consequences of placental
      oxidative stress and mitochondrial dysfunction on the course and outcomes of
      pregnancy remain to be elucidated in larger prospective studies.

PMID- 23865368
TI  - The economic evaluation of screening for colorectal cancer: Case of Iran.
AB  - BACKGROUND: Given increasing rates of colorectal cancer (CRC) in countries with
      intermediate incidence rates, the decision to implement population-based
      screening must consider the trade-off between high costs and a relatively low
      yield. We estimated the incremental cost-effectiveness ratio of 10 strategies for
      colorectal cancer screening, as well as no screening, incorporating quality of
      life, noncompliance, and data on the costs and benefits of chemotherapy in Iran.
      METHODS: We used a Markov model to measure the costs and quality-adjusted life
      expectancy of 50-year-old average-risk Iranian without screening and with
      screening by each test. In this study, we populated the model with data from the
      ministry of health and published literature. We considered costs from the
      perspective of a health insurance organization, with inflation to the 2011
      Iranian Rial converted to US dollars. We focused on three tests of the 10
      strategies considered, currently being used for population screening in some
      Iranian provinces (Mazandaran Kerman, Golestan, Ardabil, and Tehran): low
      sensitivity guaiac fecal occult blood test, performed annually; fecal
      immunochemical test, performed annually; and colonoscopy, performed every 10
      years. RESULTS: These strategies reduced the incidence of colorectal cancer by
      39%, 60%, and 76% and mortality by 50%, 69%, and 78%, respectively, compared with
      no screening. These strategies generated ICER (incremental cost-effectiveness
      ratios) of $9067, $654, and $8700 per QALY (quality-adjusted life year),
      respectively. Sensitivity analyses were performed to evaluate the influence of
      various parameters on the cost-effectiveness of screening. The results were
      robust to probabilistic sensitivity analysis. Colonoscopy every 10 years yielded
      the greatest net health benefit. CONCLUSIONS: Screening for colorectal cancer is
      cost-effective over conventional levels of WTP (Willingness to Pay). Annual high
      sensitivity fecal occult blood testing, such as a fecal immunochemical test, or
      colonoscopy every 10 years offer the best value for the money in Iran.

PMID- 23865369
TI  - Peculiar genotypes of the autoimmune regulator gene in Italian patients with
      autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.
AB  - BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
      (APECED) is due to mutations in the autoimmune regulator gene (AIRE). The highest
      number of patients was reported in Finland and among other ethnic groups such as
      Iranian Jews. Hot spots of incidence are also in Italian regions including
      Sardinia, Apulia, and the Venetian region, where peculiar AIRE genotypes were
      identified. METHODS: We conducted screenings of all the 14 exons of the AIRE gene
      in 5 APECED patients from 3 different Italian regions. RESULTS: We confirmed the
      peculiar Sardinian R139X genotype in 2 Sardinians and unusually in one patient
      from the Venetian region. As expected, exon 1 mutation was detected in one
      patient from Campania, while the other with the novel c.1314-1326del13/insGT
      mutation in exon 11 and already described, presented candidiasis and autoimmune
      hepatitis as first symptoms. No genotype/phenotype correlation was observed in
      the remaining patients. CONCLUSIONS: Testing AIRE genotypes is useful to confirm
      an APECED diagnosis but also in investigating the pathogenesis and epidemiology
      of the disease in different regions.

PMID- 23865370
TI  - A case of toxic epidermal necrolysis with diverse etiologies: successful
      treatment with intravenous immunoglobulin and pulse prednisolone and effects on
      sTRAIL and sCD200 levels.
AB  - BACKGROUND: Here, we report the first case of patient with intracranial tumors
      (ICT) who developed a cutaneous adverse drug reaction during lansoprazole and
      prophylactic anticonvulsant treatment. SCORTEN is a scoring system used to
      predict mortality in TEN patients. If SCORTEN index is 5 or more, mortality rate
      is more than 90%. SCORTEN of our patient was calculated as 5. METHODS: Our
      patient is a 64 year-old white female, who had glioma and had been on post-op
      prophylactic anticonvulsant therapy. On the 3rd day post operation, lansoprazole
      was added to the therapy. After the first lansoprazole dose, erythematous dusky
      red macules occurred on extremities and trunk and on the following day confluent
      purpuric lesions tended to run together in 95% of the whole body including scalp,
      oral and genital mucosa. Nikolsky's Sign was positive on the skin. Physical
      examination; body temperature was 38.4 degrees C with a heart rate of 146
      beats/minute and 80/50 mm Hg arterial blood pressure, Glascow Coma Scale was E1
      M1e, pupillary light reflex was 2/2 +/+ and she was confused. Her biopsy resulted
      as toxic epidermal necrolysis. Moreover, sTRAIL and sCD200 levels of serum and
      blister fluid were investigated as an apoptotic marker and a negative marker for
      inflammation. RESULTS AND CONCLUSIONS: sTRAIL and sCD200 were evaluated both in
      the sera and blister fluid. sTRAIL level was lower than for healthy individuals
      with high levels in blister fluid; and sCD200 level was depressed by up to 10% of
      the normal values of healthy individuals but with high levels in the blister
      fluid during the active phase of the disease. After our successful treatment with
      human albumin, prednisolone pulse therapy, and IVIG at a dose of 400 mg/kg, she
      was discharged from the hospital on the 23rd day and followed up after 2 months.
      The increase in sTRAIL (up to two-fold) and sCD200 (up to six-fold) levels may
      provide useful information in understanding disease pathogenesis and monitoring
      treatment efficacy.

PMID- 23865371
TI  - Total antioxidant capacity and ischemia modified albumin in beta thalassemia.
AB  - BACKGROUND: Total antioxidant capacity (TAC) and ischemia modified albumin (IMA)
      are common parameters used to assess the status of oxidative stress under
      different conditions. This study reports on TAC and levels of IMA in patients
      with beta-thalassemia major. METHODS: Blood specimens were collected from 98
      subjects (55 beta-thalassemia major patients and 43 healthy controls). Serum
      levels of IMA and TAC were determined using conventional biochemical methods.
      Serum levels of ferritin, iron, TIBC, ALT, bilirubin, total protein, and albumin
      were measured using automated chemistry analyzers. RESULTS: Levels of TIBC were
      significantly lower, and those of ferritin, iron, percentage of transferrin
      saturation, ALT, total and direct bilirubin were significantly higher in patients
      than in controls. No significant differences were observed between patients and
      controls with respect to total protein and albumin. TAC levels, expressed as mM
      Trolox equivalents, were significantly lower in patients than in controls (0.197
      +/- 0.106 vs. 0.274 +/- 0.122, p < 0.01). Serum levels of IMA (ABSU) were
      significantly higher in patients than in controls (0.543 +/- 0.124 vs. 0.452 +/-
      0.085, p < 0.01). Spearman univariate analysis demonstrated significant inverse
      correlations of TAC with both IMA and ferritin (r = -0.307, p < 0.05 and r = 
      0.395, p < 0.01, respectively) and significant direct correlation of IMA with
      ferritin (r = 0.519, p < 0.01). CONCLUSIONS: This study demonstrates the presence
      of a significant inverse correlation between total antioxidant capacity and IMA;
      this further argues for the inclusion of IMA as one of the oxidative stress
      markers in thalassemic patients.

PMID- 23865372
TI  - Detection of beta-thalassemia/hemoglobin E disease in samples which initially
      were diagnosed as homozygous hemoglobin E.
AB  - BACKGROUND: Differentiation of beta-thalassemia/HbE disease from homozygous HbE
      in samples containing HbA2/E > 75% and HbF < 15% is difficult. The aim of this
      study is to observe the possibility of using Hb typing and hematological
      parameters to identify both disorders. METHODS: Multiplex amplification
      refractory mutation system (MARMS)-PCR for beta-thalassemia codons 17 (A > T),
      41/42 (-TCTT), 71/72 (+A), and IVSI-ntl (G > T) mutations and ARMS-PCR for HbE
      were performed in 67 samples that contained HbA2/E > 75% and HbF < 15%. RESULTS:
      Beta-thalassemia/HbE disease was identified in 10 of 67 (14.93%) samples. Levels
      of hemoglobin, hematocrit, and mean corpuscular volume (MCV) of beta
      thalassemia/HbE disease were significantly lower than those of homozygous HbE
      whereas, levels of HbF were significantly higher. CONCLUSIONS: In places where
      the molecular analysis is not available, HbF > 5% in combination with MCV < 55
      fL, hemoglobin < 100 g/L, and hematocrit < 0.30 L/L could be used for screening
      of beta-thalassemia/HbE disease.

PMID- 23865373
TI  - Rapid influenza virus test.

PMID- 23865374
TI  - Evaluation of rapid influenza virus tests in patients with influenza-like illness
      in Thailand.

PMID- 23865375
TI  - Escherichia coli heptosyltransferase I: investigation of protein dynamics of a GT
      B structural enzyme.
AB  - Heptosyltransferase I (HepI), the enzyme responsible for the transfer of l
      glycero-d-manno-heptose to a 3-deoxy-alpha-d-manno-oct-2-ulopyranosonic acid
      (Kdo) of the growing core region of lipopolysaccharide, is a member of the GT-B
      structural class of enzymes. Crystal structures have revealed open and closed
      conformations of apo and ligand-bound GT-B enzymes, implying that large-scale
      protein conformational dynamics play a role in their reaction mechanism. Here we
      report transient kinetic analysis of conformational changes in HepI reported by
      intrinsic tryptophan fluorescence and present the first real-time evidence of a
      GT-B enzyme undergoing a substrate binding-induced transition from an open to
      closed state prior to catalysis. 

PMID- 23865376
TI  - Direct observation of reductive elimination of MeX (X = Cl, Br, I) from Rh(III)
      complexes: mechanistic insight and the importance of sterics.
AB  - Rare cases of directly observed reductive elimination (RE) of methyl halides from
      Rh(III) complexes are described. Treatment of the coordinatively unsaturated
      complexes [((t)BuPNP)Rh(CH3)X][BF4] (1-3, X = I, Br, and Cl; (t)BuPNP = 2,6-bis
      (di-tert-butylphosphinomethyl)pyridine) with coordinating and noncoordinating
      compounds results in the formation of the corresponding free methyl halides and
      Rh(I) complexes. The rate increase of CH3I and CH3Br RE in the presence of polar
      aprotic solvents argues in favor of an SN2 RE mechanism. However, the RE of CH3Cl
      is faster in polar protic solvents, which argues in favor of a concerted C-Cl RE.
      The RE of methyl halides from complexes 1-3 is induced by steric factors, as
      treatment of the less bulky complexes [((i)PrPNP)Rh(CH3)X][BF4] (19-21; X = I,
      Br, Cl, respectively) with coordinating compounds leads to the formation of the
      adducts complexes rather than RE of the methyl halides. The accumulated evidence
      suggests that the RE process is nonassociative. 

PMID- 23865377
TI  - Triclosan exposure increases triclosan resistance and influences taxonomic
      composition of benthic bacterial communities.
AB  - Triclosan (TCS) is a broad-spectrum antimicrobial compound that is incorporated
      into numerous consumer products. TCS has been detected in aquatic ecosystems
      across the U.S., raising concern about its potential ecological effects. We
      conducted a field survey and an artificial stream experiment to assess effects of
      TCS on benthic bacterial communities. Field sampling indicated that TCS
      concentrations in stream sediments increased with degree of urbanization. There
      was significant correlation between sediment TCS concentration and the proportion
      of cultivable benthic bacteria that were resistant to TCS, demonstrating that the
      levels of TCS present in these streams was affecting the native communities. An
      artificial stream experiment confirmed that TCS exposure could trigger increases
      in TCS resistance within cultivable benthic bacteria, and pyrosequencing analysis
      indicated that TCS resulted in decreased benthic bacterial diversity and shifts
      in bacterial community composition. One notable change was a 6-fold increase in
      the relative abundance of cyanobacterial sequences and a dramatic die-off of
      algae within the artificial streams. Selection of cyanobacteria over algae could
      have significant implications for higher trophic levels within streams. Finally,
      there were no observed effects of TCS on bacterial abundance or respiration
      rates, suggesting that bacterial density and function were highly resilient to
      TCS exposure. 

PMID- 23865378
TI  - Copper-catalyzed P-arylation via direct coupling of diaryliodonium salts with
      phosphorus nucleophiles at room temperature.
AB  - A new method for copper-catalyzed P-C bond formation through reaction of
      phosphorus nucleophiles with diaryliodonium salts at room temperature is
      described. Most target products are obtained with this method in high yields
      within a short reaction time of 10 min. It can be easily adapted to large-scale
      preparations. When unsymmetrical iodonium salts are employed, nucleophilic
      substitution occurs preferentially on the sterically hindered aromatic ring or
      the more electron-deficient ring. 

PMID- 23865380
TI  - Editorial: from correlations to causation: the value of preventive interventions
      in studying pathogenic mechanisms in childhood psychiatric disorders.
AB  - The ultimate goal of all research in childhood psychiatric disorders is to
      provide knowledge that will be useful in treating or preventing illness. To be
      useful in treating or preventing illness, research studies must provide valid
      information about the causes of illness, because only by targeting those causes
      can we prevent or counter their effects in a truly rational way. Until now, the
      discovery of interventions has largely been by serendipity, yielding medications
      and behavioral interventions that produce too little therapeutic response, in too
      few people, and with too many side effects. The selection of which specific
      intervention to use for which child is based on trial-and-error guesswork and the
      personal preferences and idiosyncrasies of the treating clinician, with little or
      no empirical support, and at great cost to children, families, and health care
      systems. Guesswork in treatment will decline only when we have more detailed
      knowledge of the differing causal pathways that produce differing subtypes of the
      same disease phenotype. Identifying more homogeneous subtypes of disease that
      have more uniform natural histories and treatment responses will permit
      development of more genuinely rational and individualized interventions, or more
      truly personalized medicine (Insel, 2009). Identifying causal pathways in human
      disease, however, is especially challenging because the classic method of
      experimental investigation - isolating and manipulating at will a variable that
      is hypothesized to exert a causal influence on the illness in order to understand
      its effects on other variables - is not possible when studying the causes of
      human illness, for obvious ethical reasons. We are therefore left with a variety
      of methods for identifying probable causal pathways in human illness, all of
      which have varying strengths and limitations in the weight of evidence that they
      provide that a variable has a true causal influence on the disorder. 

PMID- 23865379
TI  - Immunohistochemical analysis of mismatch proteins in carcinogenesis of the lower
      lip.
AB  - AIM: This study investigated the immunohistochemical expression of hMLH1 and
      hMSH2 proteins in lower lip squamous cell carcinoma (SCC) and actinic cheilitis
      (AC), to contribute to the understanding of the development of lower lip cancer.
      METHODS AND RESULTS: Forty cases of lower lip AC and SCC were studied.
      Quantitative immunohistochemical analysis was undertaken by counting 1000 cells
      (positive and negative) in each lesion. Statistical evaluation included Student's
      t-test and one-way ANOVA. For SCC and AC, the mean number of hMLH1- and hMSH2
      positive cells decreased with advanced stage of the lesion. The largest mean
      number of immunostained cells was observed in AC cases without dysplasia or with
      mild dysplasia (hMLH1: 721.23 +/- 88.116; hMHS2: 781.50 +/- 156.93). Intermediate
      values were obtained for AC with moderate or severe dysplasia (hMLH1: 532.86 +/-
      197.72; hMHS2: 611.14 +/- 172.48). Lower lip SSCs presented the smallest number
      of positive cells (hMLH1: 255.03 +/- 199.47; hMHS2: 518.38 +/- 265.68). A
      statistically significant difference was observed between groups (P < 0.001).
      CONCLUSIONS: The results support the hypothesis that changes in the
      immunoexpression of these mismatch proteins are related to the process of
      carcinogenesis of the lower lip.

PMID- 23865381
TI  - Ex(2)Box: interdependent modes of binding in a two-nanometer-long synthetic
      receptor.
AB  - Incorporation of two biphenylene-bridged 4,4'-bipyridinium extended viologen
      units into a para-phenylene-based cyclophane results in a synthetic receptor that
      is ~2 nm long and adopts a box-like geometry. This cyclophane, Ex(2)Box(4+),
      possesses the ability to form binary and ternary complexes with a myriad of guest
      molecules ranging from long pi-electron-rich polycyclic aromatic hydrocarbons,
      such as tetracene, tetraphene, and chrysene, to pi-electron-poor 2,6
      dinitrotoluene, 1,2,4-trichlorobenzene, and both the 9,10- and 1,4-anthraquinone
      molecules. Moreover, Ex(2)Box(4+) is capable of forming one-to-one complexes with
      polyether macrocycles that consist of two pi-electron-rich dioxynaphthalene
      units, namely, 1,5-dinaphtho[38]crown-10. This type of broad molecular
      recognition is possible because the electronic constitution of Ex(2)Box(4+) is
      such that the pyridinium rings located at the "ends" of the cyclophane are
      electron-poor and prefer to enter into donor-acceptor interactions with pi
      electron-rich guests, while the "middle" of the cyclophane, consisting of the
      biphenylene spacer, is more electron-rich and can interact with pi-electron-poor
      guests. In some cases, these different modes of binding can act in concert to
      generate one-to-one complexes which possess high stability constants in organic
      media. The binding affinity of Ex(2)Box(4+) was investigated in the solid state
      by way of single-crystal X-ray diffraction and in solution by using UV-vis and
      NMR spectroscopy for 12 inclusion complexes consisting of the tetracationic
      cyclophane and the corresponding guests of different sizes, shapes, and
      electronic compositions. Additionally, density functional theory was carried out
      to elucidate the relative energetic differences between the different modes of
      binding of Ex(2)Box(4+) with anthracene, 9,10-anthraquinone, and 1,4
      anthraquinone in order to understand the degree with which each mode of binding
      contributes to the overall encapsulation of each guest.

PMID- 23865382
TI  - GLP-1 receptor agonists: effects on cardiovascular risk reduction.
AB  - Comorbid obesity, dyslipidemia, and hypertension place patients with type 2
      diabetes (T2DM) at greatly increased risk of cardiovascular (CV) disease-related
      morbidity and mortality. An urgent need exists for effective treatment for
      patients with T2DM that encompasses glycemic control, weight loss, and reduction
      in CV risk factors. The glucagon-like peptide-1 receptor agonists (GLP-1 RAs)
      liraglutide and exenatide are incretin-based antidiabetes agents. This review
      examines CV-associated effects of liraglutide and exenatide in animal models and
      clinical trials with patients with T2DM. Studies support the effectiveness of GLP
      1 RAs in reducing hyperglycemia. Further, GLP-1 RAs represent a significant
      advance in T2DM treatment because they uniquely affect a broad array of CV risk
      factors through significant weight and systolic blood pressure reduction,
      improved lipid levels, and possibly, as shown in in vitro studies and animal
      models, through direct effects on cardiac myocytes and endothelium. 

PMID- 23865383
TI  - Effect of simvastatin on plasma homocysteine levels and its modification by MTHFR
      C677T polymorphism in Chinese patients with primary hyperlipidemia.
AB  - OBJECTIVE: We investigate the effect of simvastatin on plasma homocysteine (Hcy)
      levels and whether genetic factor affects the effect of simvastatin. METHODS: A
      total of 338 patients with hyperlipidemia were enrolled. Simvastatin was orally
      administered at a dose of 20 mg/day for 8 weeks. Plasma Hcy levels were measured
      by high-performance liquid chromatography at baseline and after 8 weeks of
      treatment. Genotyping of methylenetetrahydrofolate reductase (MTHFR) C677T
      polymorphism was performed by TaqMan probe technique. RESULTS: Serum total Hcy
      levels were positively correlated with serum creatinine (r = 0.332, P < 0.001).
      Among total subjects, simvastatin treatment resulted in a significant reduction
      in serum Hcy levels after 8 weeks (-0.37 +/- 2.21 MUmol/L, P = 0.003), and this
      effect was dependent on the initial levels of serum Hcy. The individuals with
      677TT genotype had a significantly higher baseline Hcy level and a greater change
      in Hcy levels. After stratification by body mass index (BMI), we observed a
      significant increase in Hcy levels among the TT genotype group in adjusted model
      (beta+/-SE: 2.64 +/- 0.84 MUmol/L; P = 0.002) among patients with BMI >= 25
      (kg/m(2) ). CONCLUSIONS: Simvastatin can cause a marked decrease in plasma Hcy
      levels. MTHFR C677T genetic variant contributes to simvastatin's effects among
      Chinese subjects with primary hyperlipidemia.

PMID- 23865385
TI  - Regioselective copper-catalyzed carboxylation of allylboronates with carbon
      dioxide.
AB  - In the presence of a Cu(I)/NHC catalyst, the reactions of allylboronic pinacol
      esters with CO2 (1 atm) are highly regioselective, giving exclusively the more
      substituted beta,gamma-unsaturated carboxylic acids in most cases. A diverse
      array of substituted carboxylic acids can be prepared via this method, including
      compounds featuring all-carbon quaternary centers. 

PMID- 23865386
TI  - Pigmented mammary Paget's disease presenting with dermoscopic features of
      multiple dots.

PMID- 23865384
TI  - Transient domoic acid excitotoxicity increases BDNF expression and activates both
      MEK- and PKA-dependent neurogenesis in organotypic hippocampal slices.
AB  - BACKGROUND: We have previously reported evidence of cell proliferation and
      increased neurogenesis in rat organotypic hippocampal slice cultures (OHSC) after
      a transient excitotoxic injury to the hippocampal CA1 area induced by low
      concentrations of the AMPA/kainate agonist domoic acid (DOM). An increased
      baseline rate of neurogenesis may contribute to recovery from DOM-induced mild
      injury but the intracellular mechanism(s) responsible for neuronal proliferation
      remain unclear. The current study investigated the key intracellular pathways
      responsible for DOM-induced neurogenesis in OHSC including the effects of
      transient excitotoxicity on the expression of brain-derived neurotrophic factor
      (BDNF), a well-known regulator of progenitor cell mitosis. RESULTS: Application
      of a low concentration of DOM (2 MUM) for 24 h followed by recovery induced a
      significant and long lasting increase in BDNF protein levels expressed by both
      neurons and microglial cells. Furthermore, the mild DOM toxicity stimulated both
      PKA and MEK-dependent intracellular signaling cascades and induced a significant
      increase in BDNF- transcription factor CREB activation and BDNF-receptor TrkB
      expression. Coexposure to specific inhibitors of PKA and MEK phosphorylation
      resulted in a significant decrease in the neurogenic marker doublecortin.
      CONCLUSIONS: Our results suggest that transient excitotoxic insult induced by DOM
      produces BDNF and CREB overexpression via MEK and PKA pathways and that both
      pathways mediate, at least in part, the increased neural proliferation resulting
      from mild excitotoxicity.

PMID- 23865387
TI  - Risk factors for primary prevention of cardiovascular disease and risk reduction
      by lipid control: the OMEGA study risk factor sub-analysis.
AB  - To identify risk factors for cardiovascular disease (CVD) in hypertensive
      patients with no history of CVD being treated with antihypertensive drugs, we
      examined subgroup data (n = 13 052) from the prospective, observational
      Olmesartan Mega Study to Determine the Relationship between Cardiovascular
      Endpoints and Blood Pressure Goal Achievement (OMEGA) study. Risk factors for
      CVD, stroke and coronary heart disease (CHD) were examined using a Cox
      proportional hazards model. In addition, the effect of statin therapy at baseline
      on CHD prevention was analyzed in dyslipidemic patients. The factors
      significantly related to CVD were female (hazard ratio [HR] = 0.637, 95%
      confidence interval [CI] 0.428-0.948), older age (65-69 years: HR = 2.165, 95% CI
      1.214-3.861; 70-74 years: HR = 2.324, 95% CI 1.294-4.174; >=75 years: HR = 2.448,
      95% CI 1.309-4.578), family history of CHD (HR = 1.993, 95% CI 1.249-3.179),
      diabetes (HR = 2.287, 95% CI 1.700-3.078), current smoking (HR = 2.289, 95% CI
      1.512-3.466) and alcohol drinking socially (HR = 0.589, 95% CI 0.379-0.913).
      Diabetes was a risk factor for both stroke and CHD, while age, family history of
      CHD, and sodium intake score were risk factors for stroke alone. Sex,
      dyslipidemia, smoking and exercise habits were risk factors for CHD alone. The
      risk of CHD in dyslipidemic patients on statin treatment was comparable to the
      risk in patients without dyslipidemia (HR = 1.134, 95% CI 0.604-2.126). However,
      in dyslipidemic patients not on statin treatment, the HR increased to 1.807 (95%
      CI 1.156-2.825). In conclusion, some risk factors for CVD in hypertensive
      patients being treated with antihypertensive drugs with no history of CVD
      differed between CHD and stroke. These results suggest the importance of managing
      dyslipidemia with a statin for primary prevention of CHD, as well as the
      importance of hypertension therapy.

PMID- 23865388
TI  - Use of continuous renal replacement therapy in acute aluminum phosphide
      poisoning: a novel therapy.
AB  - Aluminum phosphide is most common cause of poisoning in northern India. There is
      no specific antidote available and management of such cases is mainly supportive
      with high mortality. We present two cases of severe acute aluminium phosphide
      poisoning where continuous renal replacement therapy (CRRT) was started early
      along with other resuscitative measures and both the patients survived.

PMID- 23865389
TI  - Association of HbA1c and cardiovascular and renal disease in an adult
      Mediterranean population.
AB  - BACKGROUND: Increasing evidence suggests a mechanistic link between the glycemic
      environment and renal and cardiovascular events, even below the threshold for
      diabetes. We aimed to assess the association between HbA1c and chronic kidney
      disease (CKD) and cardiovascular disease (CVD). METHODS: A cross-sectional study
      involving a random representative sample of 2270 adults from southern Spain
      (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in
      fasting blood and urine samples. RESULTS: Individuals without diabetes in the
      upper HbA1c tertile had an unfavorable cardiovascular and renal profile and
      shared certain clinical characteristics with the patients with diabetes. Overall,
      a higher HbA1c concentration was strongly associated with CKD or CVD after
      adjustment for traditional risk factors. The patients with known diabetes had a 2
      fold higher odds of CKD or CVD. However, when both parameters were introduced in
      the same model, the HbA1c concentration was only significantly associated with
      clinical endpoints (OR: 1.4, 95% CI, 1.1-1.6, P = 0.002). An increase in HbA1c of
      one percentage point was associated with a 30% to 40% increase in the rate of CKD
      or CVD. This relationship was apparent in persons with and without known
      diabetes. ROC curves illustrated that a HbA1c of 37 mmol/mol (5.5%) was the
      optimal value in terms of sensitivity and specificity for predicting endpoints in
      this population. CONCLUSION: HbA1c levels were associated with a higher
      prevalence of CKD and CVD cross-sectionally, regardless of diabetes status. These
      data support the value of HbA1c as a marker of cardiovascular and renal disease
      in the general population.

PMID- 23865390
TI  - Polyphenol metabolite profile of artichoke is modulated by agronomical practices
      and cooking method.
AB  - In this paper artichoke phenolic pattern was characterized using an Orbitrap
      Exactive Mass Spectrometer at high mass accuracy and conventional HPLC MS/MS.
      Twenty four phenolic acids and 40 flavonoids were identified, many of them not
      previously reported in artichoke. Variations in phenolic compounds were
      investigated in relation to mycorrhization: results showed that inoculation with
      mycorrhizae greatly influences metabolite profile proving to be a good strategy
      to enhance the biosynthesis of secondary metabolites in this plant. This practice
      also caused a different distribution of the main phenolic compounds within head
      parts. Both steaming and microwaving cooking treatments caused an increase in
      antioxidant activity: the lower the initial concentration the higher the effect.
      A similar trend was observed looking at the phenolic compounds concentration: it
      increased because of cooking treatments the lower the initial content, the
      highest the increase. Steamed artichoke showed higher phenols content than
      microwaved ones. 

PMID- 23865391
TI  - Paraspinal muscle asymmetry in Parkinson's disease.
AB  - Lateral postural deviation in Parkinson's disease (PD) is not uncommon but has
      never been radiographically queried to evaluate for specific muscle anatomy. Ten
      subjects (9 female) were identified with paraspinal asymmetry on examination and
      MRI. Relative atrophy was seen diffusely in all paraspinal muscles (psoas,
      interspinalis, quadratus, multifidus, longissimus and ileocostalis). The
      quadratus, multifidus, longissimus and ileocostalis were the most asymmetric and
      equally involved. The interspinalis was less asymmetric, whereas the psoas was
      almost never asymmetric. Fatty infiltrates, consistent with radiographic
      myopathic degeneration, were often seen in the atrophic muscles. In 8/10 cases,
      the side of PD symptom onset demonstrated the greatest atrophy. Lateral postural
      deviation appears to result from ipsilateral paraspinal atrophy with fatty
      infiltration. Correlation with the most affected side suggests causality.

PMID- 23865392
TI  - Microwave selective thermal development of latent fingerprints on porous
      surfaces: potentialities of the method and preliminary experimental results.
AB  - The thermal development of latent fingerprints on paper surfaces is a simple,
      safe, and chemicals-free method, based on the faster heating of the substrate
      underlying the print residue. Microwave heating is proposed for the first time
      for the development of latent fingerprints on cellulose-based substrate, in order
      to add to the thermal development mechanism the further characteristic of being
      able to heat the fingerprint residues to a different extent with respect to the
      substrate, due to the intrinsic difference in their dielectric properties.
      Numerical simulation was performed to confirm and highlight the selectivity of
      microwaves, and preliminary experimental results point out the great
      potentialities of this technique, which allowed developing both latent sebaceous
      rich and latent eccrine-rich fingerprints on different porous surfaces, in less
      than 30 sec time with an applied output power of 500 W. Microwaves demonstrated
      more effectiveness in the development of eccrine-rich residues, aged up to 12
      weeks. 

PMID- 23865393
TI  - Haemovigilance in 2013.

PMID- 23865394
TI  - Transfusion safety in 2012: main messages from the SHOT Annual Report for 2012.

PMID- 23865395
TI  - Blood donation associated risks: data from a Swiss regional haemovigilance
      program.

PMID- 23865396
TI  - Breaking records in blood transfusion safety: universal leucodepletion--is it
      saving us from catastrophe?

PMID- 23865399
TI  - Association between host's genetic diversity and parasite burden in damselflies.
AB  - Recent research indicates that low genetic variation in individuals can increase
      susceptibility to parasite infection, yet evidence from natural invertebrate
      populations remains scarce. Here, we studied the relationship between genetic
      heterozygosity, measured as AFLP-based inbreeding coefficient fAFLP , and
      gregarine parasite burden from eleven damselfly, Calopteryx splendens,
      populations. We found that in the studied populations, 5-92% of males were
      parasitized by endoparasitic gregarines (Apicomplexa: Actinocephalidae). Number
      of parasites ranged from none to 47 parasites per male, and parasites were highly
      aggregated in a few hosts. Mean individual fAFLP did not differ between
      populations. Moreover, we found a positive association between individual's
      inbreeding coefficient and parasite burden. In other words, the more homozygous
      the individual, the more parasites it harbours. Thus, parasites are likely to
      pose strong selection pressure against inbreeding and homozygosity. Our results
      support the heterozygosity-fitness correlation hypothesis, which suggests the
      importance of heterozygosity for an individual's pathogen resistance. 

PMID- 23865400
TI  - Ultrafast time-resolved broadband fluorescence studies of the benzene
      tetracyanoethylene complex: solvation, vibrational relaxation, and charge
      recombination dynamics.
AB  - The charge-transfer (CT) state relaxation dynamics of the benzene
      tetracyanoethylene (BZ-TCNE) complex was studied with broadband ultrafast time
      resolved fluorescence spectroscopy implemented by optical Kerr gating in three
      solvents of different polarities. The CT state of the BZ-TCNE complex is reached
      via femtosecond laser excitation, and the subsequent temporal evolutions of the
      fluorescence spectra were measured. Analyses of various time-dependent spectral
      properties revealed rapid relaxations along solvent and vibrational coordinates
      in competition with charge recombination (CR). By comparing the results in
      solvents of different polarities, we partially separated solvation and
      vibrational relaxation dynamics and explored the solvent-dependent CR dynamics.
      Time-dependent dynamic fluorescence Stokes shift (TDFSS) measurements unveiled
      the solvation and vibrational relaxation contributions to the observed spectral
      relaxation. The biphasic and slow time scales of the vibrational contributions
      identified in TDFSS suggested nonstatistical and hindered intramolecular
      vibrational-energy redistribution that can be attributed to the unique structural
      properties of EDA complexes. The slowest spectral relaxation of 10-15 ps
      identified in TDFSS was ascribed to relaxation of the BZ(+)-TCNE(-)
      intermolecular vibrations, which is equivalent to a structural relaxation from
      the initial Franck-Condon configuration to the equilibrium CT-state structure.
      The time scales of vibrational relaxation indicate that a fraction of the CT
      state population undergoes CR reactions before complete vibrational/structural
      equilibrium is achieved. In carbon tetrachloride, a nonexponential temporal
      profile was observed and attributed to vibrational nonequilibrium CR. In
      dichloromethane, polar solvation greatly accelerates CR reactions, and a slower
      reaction-field-induced structural relaxation gives rise to a pronounced
      biexponential decay. The equilibrium CR time constants of the BZ-TCNE CT state
      are 29 ps, 150 ps, and 68 ps in dichloromethane, carbon tetrachloride, and
      cyclohexane, respectively. 

PMID- 23865401
TI  - Comparison of presumptive echocardiographic and definitive diagnoses of cardiac
      tumors in dogs.
AB  - BACKGROUND: Echocardiography is used for identification of cardiac tumors and
      presumptive diagnoses often are made based on the location of identified masses.
      OBJECTIVES: To determine the accuracy of echocardiographically based presumptive
      diagnoses of cardiac tumors when compared with clinicopathologic or
      histopathologic definitive diagnoses. ANIMALS: A total of 24 client-owned dogs
      having a cardiac mass on echocardiogram that was subsequently definitively
      diagnosed by cytology or histopathology. METHODS: Retrospective study. A Cardiac
      Veterinary Database search of animals seen at the University of Tennessee John
      and Ann Tickle Small Animal Hospital from 2006 to 2012 identified 24 dogs that
      fit the inclusion criteria. RESULTS: The presumptive diagnosis of chemodectoma,
      ectopic thyroid carcinoma, or lymphoma in cases with heart base masses was
      correct in 7/9 cases. The presumptive diagnosis of hemangiosarcoma in cases with
      right atrial masses was correct in 4/8 cases. Seven cases had an open diagnosis
      because of the unusual presentation on echocardiogram (ECG); various neoplasms
      were diagnosed in these animals, but hemangiosarcoma, chemodectoma, ectopic
      thyroid carcinoma, and lymphoma accounted for 6 of them. Pericardial effusion was
      seen in 10/24 cases. ECG abnormalities were seen in 8/24 cases. Survival ranged
      from <1 to >150 days. CONCLUSIONS AND CLINICAL IMPORTANCE: In this retrospective
      study, the presumptive diagnosis based on echocardiographic tumor location was
      only moderately accurate. Cardiac tumors that were considered unusual on
      echocardiogram were nonetheless frequently found to be the common cardiac tumor
      types seen in dogs.

PMID- 23865402
TI  - Metacognitive beliefs, beliefs about voices and affective symptoms in patients
      with severe auditory verbal hallucinations.
AB  - OBJECTIVES: This study explores associations between metacognitive beliefs and
      beliefs about voices in patients with severe auditory verbal hallucinations, and
      their hypothesized relationship with levels of depression and anxiety.
      Furthermore, it was hypothesized that metacognitive beliefs are better able to
      explain differences in levels of depression and anxiety, than beliefs about
      voices. DESIGN: Cross-sectional data were obtained from baseline measurements of
      a randomized controlled trial. All patients (N = 77) met the criteria for a DSM
      IV diagnosis within the schizophrenia spectrum. A correlation analysis was
      conducted to explore the associations between metacognitive beliefs and beliefs
      about voices. Regression analysis was performed to test the second hypothesis.
      METHOD: Metacognitive beliefs were measured using the MCQ-30. Beliefs about
      voices were measured using the BAVQ-R. Furthermore, the Beck Depression Inventory
      II and the Beck Anxiety Inventory were applied to measure depression and anxiety.
      All analyses were a priori controlled for gender and level of education. RESULTS:
      Significant associations were found between negative beliefs about voices and
      negative metacognitive beliefs. One of the metacognitive beliefs, that is,
      perceived uncontrollability and danger of thinking, proved to be a key variable
      in explaining differences in levels of depression and anxiety and seemed to have
      greater explanatory value than all of the beliefs about voices when analysed
      simultaneously. CONCLUSIONS: The results offer modest support to models
      emphasizing the fact that metacognitive beliefs are a core feature in the
      development and maintenance of depression and anxiety in patients with severe
      auditory verbal hallucinations. PRACTITIONER POINTS: POSITIVE CLINICAL
      IMPLICATIONS: Further evidence for the importance of metacognitive beliefs.
      Specific emphasis on anxiety and depression in patients with severe
      hallucinations. LIMITATIONS: Small sample size. Cross-sectional data only.

PMID- 23865403
TI  - Development and validation of the supervisory relationship measure: a self-report
      questionnaire for use with supervisors.
AB  - OBJECTIVE: To develop a valid and reliable measure of the supervisory
      relationship (SR) from the perspective of the supervisor. DESIGN: A cross
      sectional self-report questionnaire design was used with a repeated component for
      a subsample. METHOD: Qualitative data from a previous study of the SR (collected
      by interviews with supervisors) were used to construct an 89-item self-report
      questionnaire measure (Supervisory Relationship Measure [SRM]). This was
      administered to 267 clinical psychology supervisors involved in supervising UK
      trainee clinical psychologists. One hundred and thirty-four participants
      completed the measure a second time to establish its test-retest reliability.
      RESULTS: Principal components analysis was used. Five factors were identified and
      labelled 'safe base', 'supervisor commitment', 'trainee contribution', 'external
      influences', and 'supervisor investment'. Fifty-one items (comprising five
      subscales based on the factors identified) were selected for the final measure.
      Analyses revealed the SRM to have good internal consistency, good test-retest
      reliability, and good construct (convergent and divergent) validity. A
      preliminary test of predictive (statistical) validity (supervisor satisfaction
      with the relationship and trainee competence as perceived by the supervisor)
      yielded promising results. CONCLUSION: The SRM is a valid and reliable measure of
      the SR from the supervisor perspective. It predicts supervisor satisfaction and
      preliminary evidence suggests that it may also predict trainee competence (as
      perceived by the supervisor). The findings are consistent with current theory on
      the SR. The SRM is, therefore, a promising tool for use in research, clinical,
      and training settings. PRACTITIONER POINTS: The supervisory relationship measure
      (SRM) is a new psychometrically sound measure of the supervisory relationship
      (SR) with clinical and research uses. Clinically, it is a useful and structured
      way for supervisors to provide constructive feedback to their trainees. It can be
      used in conjunction with the Supervisory Relationship Questionnaire (SRQ)
      (completed by the supervisee) to support a dyadic discussion about clinical
      supervision. Currently the measure is only validated on Clinical Psychology
      trainees and should be used with caution with qualified staff and other
      professional groups. Participants were predominantly white British supervisors
      who chose to take part in an internet-based study and thus the sample may not be
      fully representative of the population.

PMID- 23865404
TI  - Discrepancies in parental and self-appraisals of prosocial characteristics
      predict emotional problems in adolescents.
AB  - OBJECTIVES: Parental appraisals of an adolescent may have an effect upon the
      adolescent's well-being and likelihood of emotional problems. However, the impact
      of these parental appraisals is likely to be partly determined by the young
      person's self-appraisal. It was predicted that a discrepancy in self- and parent
      appraisals of positive, prosocial qualities would be associated with an increased
      risk of emotional problems. DESIGN: The study employed a cross-sectional design
      within a large sample of adolescent and caregiver dyads (N = 3,976, aged 11-17
      years), drawn from the 'Mental health of children and young people in Great
      Britain, 2004' survey. METHOD: Two separate measures of prosociality were used to
      ensure that effects were not specific to one measure. The analysis explored the
      discrepancy in parent and self-ratings on these measures via interactions within
      a logistic regression framework. Potential confounds, including gender, parental
      mental health, conduct and hyperkinetic problems were controlled for in the
      analysis. RESULTS: The logistic regression analyses demonstrated significant
      interactions between self- and parent ratings of prosocial qualities in
      predicting the odds of emotional disorder (i.e., depression and anxiety). This
      effect occurred across both measures of prosocial qualities whilst controlling
      for confounds. The pattern of the interactions suggested that low parental
      appraisals had a more detrimental effect on well-being when self-appraisals were
      highly positive. CONCLUSIONS: The results suggest that moderately high self
      appraised positive traits may carry a cost of leaving young people more
      vulnerable to discrepant, negative parental appraisals. This has important
      implications for the meaning attributed to self-appraised positive traits in
      clinical contexts. PRACTITIONER POINTS: Clinicians should be aware that the
      association between parental perceptions of a child's prosociality and emotional
      disorder may be influenced by the adolescents' self-perceptions. Clinicians
      should therefore endeavour to assess both parental and adolescent appraisals.
      Discrepancies may be clinically meaningful, in terms of the risk of emotional
      problems, rather than simply being a nuisance. This study is cross-sectional, so
      although discrepancies may be linked to risk of emotional problems, the direction
      of this effect requires elucidation. The current study only focusses on the
      parent-adolescent dynamic and so may not extend to discrepancy effects in other
      areas of positive functioning or in other relational contexts.

PMID- 23865405
TI  - Major depressive disorder and impulsive reactivity to emotion: toward a dual
      process view of depression.
AB  - OBJECTIVE: Dual-process theories of behaviour have been used to suggest that
      vulnerability to depression involves elevated reactivity to emotions. This study
      tests that idea, examining self-reported reactivity. DESIGN: Comparison between
      persons with at least one lifetime episode of major depressive disorder (lifetime
      MDD) and those without this diagnosis, controlling for symptoms of alcohol use (a
      potential externalizing confound) and current symptoms of depression (a potential
      state-dependent confound). METHODS: Undergraduates (N = 120) completed a clinical
      interview to diagnose lifetime MDD and a series of self-reports bearing on
      diverse aspects of self-control, including reactivity to emotion. Thirty-four
      people were diagnosed with lifetime MDD; 86 did not meet criteria for MDD. The
      groups were then compared on three factors underlying the scales assessing self
      control. RESULTS: The MDD group had higher scores than controls on the two
      factors that reflect impulsive reactivity to diverse emotions, including emotions
      that are positive in valence. These effects were not explained by associations
      with either externalizing symptoms or current depressive symptoms. CONCLUSIONS:
      Reflexive reactivity to emotions characterizes depression, in addition to some
      externalizing problems, and it may deserve study as a potential trans-diagnostic
      feature. PRACTITIONER POINTS: Reflexive reactivity to emotions characterizes
      persons diagnosed with major depressive disorder. Findings suggest desirability
      of focusing treatment partly on management of reflexive reactions to emotions.
      LIMITATION: Measures were self-reports, rather than behavioural responses to
      emotions.

PMID- 23865406
TI  - The association between obsessive compulsive disorder and obsessive compulsive
      personality disorder: prevalence and clinical presentation.
AB  - OBJECTIVES: The relationship between Obsessive Compulsive Disorder (OCD) and
      Obsessive Compulsive Personality Disorder (OCPD) has been the subject of interest
      for some time due to the historical assumption that OCPD causes OCD. This study
      systematically examined the association between OCD and OCPD in terms of
      prevalence and clinical presentation. The specificity of the association between
      OCD and OCPD was investigated relative to another axis I anxiety disorder (Panic
      disorder). DESIGN AND METHOD: Data for this study were drawn from measures taken
      at initial assessment at a specialist treatment centre for anxiety disorders. Of
      the 359 participants included in this study, 189 had a principal diagnosis of
      OCD, while 170 had a principal diagnosis of Panic disorder. Measures included
      SCID I and II interview modules and self-report measures of anxiety, depression,
      and OCD syptomatology. RESULTS: Significantly elevated rates of OCPD were found
      in OCD relative to Panic disorder. Regardless of axis I disorder, individuals
      with comorbid OCPD reported more severe depression relative to those without.
      Participants with both OCD and OCPD had greater self-reported OCD symptom
      severity, doubting, ordering, and hoarding symptoms at assessment relative to
      those without OCPD. Participants with OCD and comorbid OCPD also reported
      significantly higher levels of alcohol consumption. CONCLUSIONS: There appears to
      be a significant and specific association between OCD and OCPD. Co-occurring OCD
      and OCPD is associated with greater severity of impairment in terms of certain
      OCD symptoms. PRACTITIONER POINTS:  CLINICAL IMPLICATIONS: The significant and
      specific association between OCD and OCPD suggests that OCPD occurs more
      frequently with OCD than previously suggested. A comorbid OCPD diagnosis is
      associated with a greater degree of depression, regardless of axis I disorder,
      either OCD or Panic disorder. This is an important consideration, as depression
      can interfere with therapeutic progress (Foa, 1979). Participants with OCD and
      OCPD had greater self-reported OCD severity, along with doubting, ordering, and
      hoarding symptoms, relative to those without OCPD. In clinical practice, where
      OCD symptoms are severe, and the primary OCD symptoms include doubting, ordering,
      and hoarding, this may indicate a need to assess for comorbid OCPD. This may be
      useful in terms of including relevant information in formulation with the
      patient, and in addressing these issues in treatment. LIMITATIONS OF THE STUDY:
      There may have been a sampling issue, as the study compared patients from a
      specialist clinic for the treatment of OCD and Panic disorder. Furthermore, OCD
      referrals were primary, secondary, or tertiary, whereas Panic disorder referrals
      were primary or secondary from the immediate catchment area only. This suggests
      the possibility of greater severity of the OCD sample relative to Panic disorder
      patients. All participants who met criteria for OCD were assessed for OCPD
      regardless of whether or not this was indicated by the SCID II screener self
      report measure, while participants with Panic disorder were interviewed for OCPD
      only if indicated by the SCID-II screener. Had participants with Panic disorder
      been assessed for OCPD regardless of whether or not this was indicated by the
      SCID-II screener, there is a possibility that a higher rate of OCPD in the Panic
      disorder sample may have been found.

PMID- 23865407
TI  - An experimental investigation of emotional reasoning processes in depression.
AB  - OBJECTIVES: Cognitive models of depression emphasize how distorted thoughts and
      interpretations contribute to low mood. Emotional reasoning is considered to be
      one such interpretative style. We used an experimental procedure to determine
      whether elevated levels of emotional reasoning characterize depression. METHODS:
      Participants who were currently experiencing a major depressive episode (n = 27)
      were compared with those who were non-depressed (n = 25 who had never been
      depressed and n = 26 previously but not currently depressed) on an emotional
      reasoning task. RESULTS: Although there were some trends for depressed
      participants to show greater levels of emotional reasoning relative to non
      depressed participants, none of these differences attained significance.
      Interestingly, previously depressed participants engaged in more non-self
      referent emotional reasoning than never-depressed participants. CONCLUSIONS:
      Emotional reasoning does not appear to characterize mild to moderate levels of
      depression. The lack of significant differences in emotional reasoning between
      currently depressed and non-depressed participants may have been a consequence of
      the fact that participants in our currently depressed group were, for the most
      part, only mildly depressed. Non-self-referent emotional reasoning may
      nevertheless be a risk factor for subsequent depressive episodes, or else serve
      as a 'cognitive scar' from previous episodes. PRACTITIONER POINTS:  CLINICAL
      IMPLICATIONS: In contrast with the predictions of cognitive models of depression,
      emotional reasoning tendencies may not be especially prominent in currently
      depressed individuals. Depressed individuals vary greatly in the degree to which
      they engage in emotional reasoning. Individuals with remitted depression may show
      elevated of levels non-self-referent emotional reasoning compared with those who
      have never had a depressive episode, that is, rely on their emotions when forming
      interpretations about situations. LIMITATIONS: Our findings require replication
      using alternative indices of emotional reasoning. Our currently depressed
      individuals were only mildly clinically depressed precluding conclusions about
      individuals with more severe levels of depression.

PMID- 23865408
TI  - The role of metacognitive beliefs in the proneness to hallucinations and
      delusions: an analysis across clinical and non-clinical populations.
AB  - OBJECTIVES: This study explored specific and differential effects of
      metacognitive beliefs on proneness to both hallucinations and delusions in a
      general population sample, including a control for the alternate symptom. The
      study then examined whether similar findings were reproduced in a sample of
      people with psychotic disorders. DESIGN: Linear and hierarchical regressions were
      used to determine the role of metacognitive beliefs in the proneness to symptoms,
      whilst ANCOVAs analysed group differences. METHODS: Participants were recruited
      to a non-clinical sample (N = 133) and a psychosis sample (N = 100). Both groups
      completed the Launay-Slade Hallucinations Scale-Revised (Laroi et al., ; Eur.
      Psychiatry, 19, 15), the Peters Delusions Inventory (Peters et al., ; Schizophr.
      Bull., 25, 553), and the Metacognitions Questionnaire-30 (Wells & Cartwright
      Hatton, ; Behav. Res. Ther., 42, 385). RESULTS: Metacognitions were predictive of
      both hallucination- and delusion-proneness in the non-clinical sample. Controlled
      analyses in the non-clinical sample revealed specific effects: low cognitive
      confidence (CC) predicted hallucination-proneness, whilst negative beliefs about
      the uncontrollability and danger of thoughts (NBUD) predicted delusion-proneness.
      Mean ratings on NBUD, low CC, and need to control thoughts were elevated in the
      psychosis sample; however, after controlling for comorbid symptoms, no
      metacognitive belief predicted symptom-specific vulnerability in the clinical
      sample. CONCLUSIONS: The pattern of findings provided little support for
      Morrison's theoretical model of symptom-proneness. Metacognitive beliefs may be
      related to sub-acute vulnerability to psychosis symptoms; however, the
      specificity of the relationship between individual metacognitive beliefs and
      positive psychosis symptoms appeared no longer significant in psychosis patients.
      The possibility that these metacognitive beliefs are evoked by psychotic
      experiences, rather than primarily functioning as a driver of them, warrants
      greater attention. PRACTITIONER POINTS:  CLINICAL IMPLICATIONS: Metacognitive
      beliefs appear at least equally associated with delusion-proneness as
      hallucination-proneness. Negative metacognitive beliefs appear more central to
      delusion-proneness than hallucination-proneness in the general population. When
      controlling for alternate symptom, no individual metacognitive belief appears
      reliably able to predict symptom-proneness in psychosis patients. LIMITATIONS:
      Consistent with existing literature on metacognitions in psychosis, this study
      adopted a cross-sectional design, meaning we were unable to determine the causal
      direction of the observed associations between metacognitive beliefs and symptom
      proneness. Although a strength of this study design was its control for alternate
      psychotic symptoms, we did not control for non-psychotic symptoms, particularly,
      anxiety and depression. The symptom measures used were developed primarily for
      assessment of psychosis-proneness within the general population; thus, their use
      by people with established psychosis may have been less sensitive to clinical
      manifestations of these phenomena.

PMID- 23865410
TI  - Perioperative antibiotic use of dermatologic surgeons in 2012.
AB  - BACKGROUND: Recommendations for antibiotic prophylaxis in dermatologic surgery
      have been established, but there is variability in perioperative antibiotic use
      of dermatologists. Authoritative guidelines have shifted away from routine use of
      antibiotic prophylaxis because there is no conclusive evidence that antibiotic
      use reduces risk of infective endocarditis or prosthetic joint infection.
      OBJECTIVE: To determine current practices of perioperative antibiotic use of Mohs
      trained surgeons and to compare patterns of use with updated administration
      guidelines. METHODS AND MATERIALS: A survey was sent to American College of Mohs
      Surgery members in 2012. The main outcome measures were survey responses relating
      to demographic characteristics, experience with postoperative infection,
      familiarity with antibiotic guidelines, perioperative antibiotic practices,
      attitudes regarding antibiotic use, and antibiotic selection. RESULTS: Most
      survey respondents are familiar with the Antibiotic Prophylaxis in Dermatologic
      Surgery Advisory Statement 2008, but respondents give antibiotics for more
      indications than are recommended. Although not recommended, a high percentage
      reported giving antibiotics to patients at high risk of infective endocarditis or
      joint infection even when surgery does not breach oral mucosa or involve infected
      skin. CONCLUSION: Dermatologic surgeons overuse perioperative antibiotics for
      prevention of surgical site infection, infective endocarditis, and prosthetic
      joint infection based on current recommendations.

PMID- 23865409
TI  - Genome-wide identification of binding sites for NAC and YABBY transcription
      factors and co-regulated genes during soybean seedling development by ChIP-Seq
      and RNA-Seq.
AB  - BACKGROUND: Two plant-specific transcription factors, NAC and YABBY, are involved
      in important plant developmental processes. However their molecular mechanisms,
      especially DNA binding sites and co-regulated genes, are largely unknown during
      soybean seedling development. RESULTS: In order to identify genome-wide binding
      sites of specific members of the NAC and YABBY transcription factors and co
      regulated genes, we performed Chromatin Immunoprecipitation Sequencing (ChIP-Seq)
      and RNA Sequencing (RNA-Seq) using cotyledons from soybean seedling developmental
      stages. Our RNA-Seq data revealed that these particular NAC and YABBY
      transcription factors showed a clear pattern in their expression during soybean
      seedling development. The highest level of their expression was found in seedling
      developmental stage 4 when cotyledons undergo a physiological transition from non
      photosynthetic storage tissue to a metabolically active photosynthetic tissue.
      Our ChIP-Seq data identified 72 genes potentially regulated by the NAC and 96
      genes by the YABBY transcription factors examined. Our RNA-Seq data revealed
      highly differentially expressed candidate genes regulated by the NAC
      transcription factor include lipoxygense, pectin methyl esterase inhibitor,
      DEAD/DEAH box helicase and homeobox associated proteins. YABBY-regulated genes
      include AP2 transcription factor, fatty acid desaturase and WRKY transcription
      factor. Additionally, we have identified DNA binding motifs for the NAC and YABBY
      transcription factors. CONCLUSIONS: Genome-wide determination of binding sites
      for NAC and YABBY transcription factors and identification of candidate genes
      regulated by these transcription factors will advance the understanding of
      complex gene regulatory networks during soybean seedling development. Our data
      imply that there is transcriptional reprogramming during the functional
      transition of cotyledons from non-photosynthetic storage tissue to metabolically
      active photosynthetic tissue.

PMID- 23865411
TI  - Assessing outcome of diabetic foot ulcers and multidisciplinary foot clinic.
AB  - Foot problem has been increasingly recognised as a major complication of
      diabetes, which is associated with a very high mortality and morbidity. Therefore
      Multi-Disciplinary Foot Clinics (MDFC) have been established all over the world
      to provide holistic care to these patients. There is a wide variation in the
      availability of a range of professional skills in the MDFC in different health
      economy. Therefore the care provided by these MDFC can vary from one place to
      other. It is very important to measure the outcome of these MDFC so that
      patients, regulatory authorities and funding bodies can compare them.
      Traditionally ulcer related outcomes such as the healing rate and the proportion
      of ulcers healed have been measured in many foot ulcer studies. Similarly the
      amputation rate is measured to determine the efficacy of diabetic foot management
      in an area of the health economy. However, these measures do not take into
      account other important factors such as the functional ability and the quality of
      life of patients. Therefore patient related outcomes such as the recurrence of
      ulcer, number of working days lost, the mobility of patient following treatment,
      survival following first episode of ulceration etc also needs to be measured,
      which are very important from the patient's perspective. This review looks into
      various patient related outcomes that can and should be measured to assess the
      quality of care provided by the MDFC. 

PMID- 23865412
TI  - An insight into the recent diabetes trials: what is the best approach to prevent
      macrovascular and microvascular complications?
AB  - Type 2 diabetes mellitus (T2DM) accounts for 90%-95% of all diabetes cases. The
      overarching goal in caring for patients with T2DM is to prevent microvascular and
      macrovascular complications with glycemic control. Several studies such as UKPDS,
      DCCT, and EDIC have been performed to evaluate the effects of glucose control on
      tissue complications in patients with diabetes. In recent diabetes trials
      including ACCORD, ADVANCE, VADT, BARI 2D, and ORIGIN, intensive glucose control
      did not prevent macrovascular complications in older patients with long-standing
      diabetes with either cardiovascular disease or risk factors for cardiovascular
      disease. In fact, intensive therapy was associated with increased mortality in
      the ACCORD trial. Although no clear macrovascular benefit was seen in these
      trials, analyses of earlier studies in younger patients with type 1 and type 2
      diabetes have suggested a significant benefit of intensive glycemic control in
      patients with a shorter duration of diabetes and less vasculopathy. In the UKPDS,
      the incidence of microvascular disease, particularly retinopathy, was reduced
      significantly with intensive glucose control, but in the more recent trials
      (ACCORD, ADVANCE, VADT, ORIGIN) the benefit was relatively modest and limited to
      reduced proteinuria. Perhaps the most important message from the above trials is
      to optimize control of cardiovascular risk factors. Although the goal HbA1c to
      prevent microvascular and macrovascular complications, per the American Diabetes
      Association, is less than 7%, hypoglycemia should be avoided as it can increase
      the risk for severe cardiovascular events. 

PMID- 23865413
TI  - Immunomodulation in inflammatory neuropathies: rationale and safety.
AB  - Inflammatory neuropathies are treatable immune-mediated disorders of the
      peripheral nerves, the prevalence of which is higher than previously believed.
      Although there are now established treatments of proven benefit for acute and
      chronic inflammatory neuropathies consisting of intravenous immunoglobulins,
      corticosteroids and plasma exchanges, there are patients who fail to respond to
      these therapies. Immunosuppressants have been used in these refractory patients
      and also to lower the requirements of therapies of established efficacy due to
      their cost (e.g. immunoglobulins) or sideeffects (e.g., corticosteroids). These
      drugs include "conventional" immunosuppressants like azathioprine,
      cyclophosphamide etc. and also newer drugs like Rituximab. Other immunomodulatory
      drugs like interferon beta have also been trialled in some patients. Currently
      the role of newer drugs like Fingolimod in inflammatory neuropathies is being
      studied. In this article, the issue of treating inflammatory neuropathies with
      immunomodulatory and immunosuppressive agents in the context of their potential
      adverse effects, is reviewed and discussed. The published evidence on these drugs
      is reviewed, rationale behind the use of such drugs is analyzed and benefit to
      risk ratio highlighted. 

PMID- 23865414
TI  - MRI findings and renal function in patients on lithium therapy.
AB  - BACKGROUND: Lithium is one of the most effective medications in the treatment of
      mood disorders. The long-term lithium therapy can alter kidney morphology and
      function. OBJECTIVE: To evaluate the relation of Magnetic resonance imaging (MRI)
      of the kidneys and renal function in patients undergoing chronic lithium therapy.
      METHODS: Thirty five consecutive patients with mood disorders who were undergoing
      lithium therapy for at least two years were evaluated with a 1.5 tesla MR imaging
      and renal function tests. The relationship between renal size, the presence,
      number and location of renal microcyst with renal function were evaluated. The
      partial correlation analysis was performed to assess correlation between
      variables. RESULTS: The mean size of kidney was 106.0 mm +/- 6.0 and 106.0 mm +/-
      11.0 in right and left kidneys respectively. The mean number of microcysts in
      both kidneys was 6.2. There was a positive correlation between duration of
      lithium treatment and number of renal microcyst (P-value=0.03). Correlation
      between MRI findings and renal function tests was not statistically significant.
      CONCLUSION: The present study revealed that longer duration of lithium therapy
      can increase number of renal microcysts which is well shown with MR imaging. It
      seems that increasing renal microcysts may not be consistent with renal function
      impairment especially in earlier treatment phase. Thus the question arises is
      that MRI may not be as the first line method for clinicians who aim to assess
      renal function during long term lithium therapy.

PMID- 23865415
TI  - Emerging role of JNK in insulin resistance.
AB  - Insulin resistance is closely associated with obesity and type 2 diabetes.
      Although the mechanisms of insulin resistance are not fully elucidated, recent
      studies suggest that a complex interaction between inflammation, endoplasmic
      reticulum stress, oxidative stress, mitochondrial dysfunction and autophagy
      dysregulation plays an important role in insulin resistance. The stress-activated
      c-Jun N-terminal kinase (JNK) has been increasingly recognized as a central
      mediator of insulin resistance. JNK mediates many of the effects of stress on
      insulin resistance through inhibitory phosphorylation of insulin receptor
      substrate, and suppression of the JNK pathway has been shown to improve insulin
      resistance and glucose tolerance. Therefore JNK may serve as a crucial link
      between stress and metabolic diseases as well as a promising therapeutic target.
      This review focuses on recent findings that support a critical role for JNK in
      the development of insulin resistance associated with inflammation, endoplasmic
      reticulum stress, oxidative stress and mitochondrial dysfunction. JNK regulation
      of autophagy and its implications in insulin resistance also will be discussed. 

PMID- 23865416
TI  - A review on natural products for controlling type 2 diabetes with an emphasis on
      their mechanisms of actions.
AB  - The use of natural products is very common among non-industrialized societies
      because these remedies are more accessible and affordable than modern
      pharmaceuticals. In developed countries, use of herbal products has recently
      increased as scientific evidence about their effectiveness has become broadly
      available. For the past two decades many research articles in the field of ethno
      pharmacology have focused on the anti-diabetic effects of some natural products.
      This dramatic increase of interest was partly due to the fact that type 2
      diabetes mellitus (T2DM) was considered as becoming a global epidemic health
      problem which imposed high cost to national health services around the world. We
      have no intention to advocate for replacing conventional pharmacotherapy with
      natural products to prevent and control T2DM. However, the fact that a lack of
      highly effective drug-therapy with existing synthetic agents and their resulting
      adverse effects motivated further search into traditional medicine in order to re
      evaluate old remedies as well as screening to find new natural entities to be
      used as anti-diabetic products cannot be ignored. Some recent reports on the
      natural products with anti-diabetic effects have provided evidence for possible
      mechanisms of action. Nonetheless, the majority of investigators only speculated
      on a wide range of possible mechanisms or simply demonstrated an anti
      hyperglycemic effect for the crude plant extracts or the isolated compounds of
      interest. A few reviews with less attention paid to mechanisms of action have
      been published on medicinal plants and diabetes. This article reviews
      publications on anti-diabetic natural products that have appeared in PUBMED or
      other research-related literature found on the Internet (from 1990 to present) to
      categorize them based on their mechanisms of action. We hope that this
      communication will be beneficial as a starting point to consider the discussed
      products for further investigations to identify and develop new remedies with
      potential alternative or complementary use in controlling T2DM. 

PMID- 23865417
TI  - Dynamic compartment specific changes in glutathione and ascorbate levels in
      Arabidopsis plants exposed to different light intensities.
AB  - BACKGROUND: Excess light conditions induce the generation of reactive oxygen
      species (ROS) directly in the chloroplasts but also cause an accumulation and
      production of ROS in peroxisomes, cytosol and vacuoles. Antioxidants such as
      ascorbate and glutathione occur in all cell compartments where they detoxify ROS.
      In this study compartment specific changes in antioxidant levels and related
      enzymes were monitored among Arabidopsis wildtype plants and ascorbate and
      glutathione deficient mutants (vtc2-1 and pad2-1, respectively) exposed to
      different light intensities (50, 150 which was considered as control condition,
      300, 700 and 1,500 MUmol m(-2) s(-1)) for 4 h and 14 d. RESULTS: The results
      revealed that wildtype plants reacted to short term exposure to excess light
      conditions with the accumulation of ascorbate and glutathione in chloroplasts,
      peroxisomes and the cytosol and an increased activity of catalase in the leaves.
      Long term exposure led to an accumulation of ascorbate and glutathione mainly in
      chloroplasts. In wildtype plants an accumulation of ascorbate and hydrogen
      peroxide (H2O2) could be observed in vacuoles when exposed to high light
      conditions. The pad2-1 mutant reacted to long term excess light exposure with an
      accumulation of ascorbate in peroxisomes whereas the vtc2-1 mutant reacted with
      an accumulation of glutathione in the chloroplasts (relative to the wildtype) and
      nuclei during long term high light conditions indicating an important role of
      these antioxidants in these cell compartments for the protection of the mutants
      against high light stress. CONCLUSION: The results obtained in this study
      demonstrate that the accumulation of ascorbate and glutathione in chloroplasts,
      peroxisomes and the cytosol is an important reaction of plants to short term high
      light stress. The accumulation of ascorbate and H2O2 along the tonoplast and in
      vacuoles during these conditions indicates an important route for H2O2
      detoxification under these conditions.

PMID- 23865418
TI  - Baseline characteristics and prevalence of cardiovascular disease in newly
      visiting or referred chronic kidney disease patients to nephrology centers in
      Japan: a prospective cohort study.
AB  - BACKGROUND: About 39,000 patients were newly prescribed renal replacement therapy
      in Japan in 2011, resulting in a total of more than 300,000 patients being
      treated with dialysis. This high prevalence of treated end stage kidney disease
      (ESKD) patients is an emergent problem that requires immediate attention. We
      launched a prospective cohort study to evaluate population specific
      characteristics of the progression of chronic kidney disease (CKD). In this
      report, we describe the baseline characteristics and risk factors for
      cardiovascular disease (CVD) prevalence among this cohort. METHODS: New patients
      from 16 nephrology centers who were older than 20 years of age and who visited or
      were referred for the treatment of CKD stage 2-5, but were not on dialysis
      therapy, were recruited in this study. At enrollment, medical history, lifestyle
      behaviors, functional status and current medications were recorded, and blood and
      urine samples were collected. Estimated glomerular filtration rate (eGFR) was
      calculated by a modified three-variable equation. RESULTS: We enrolled 1138
      patients, 69.6% of whom were male, with a mean age of 68 years. Compared with
      Western cohorts, patients in this study had a lower body mass index (BMI) and
      higher proteinuria. The prevalence of CVD was 26.8%, which was lower than that in
      Western cohorts but higher than that in the general Japanese population.
      Multivariate analysis demonstrated the following association with CVD prevalence:
      hypertension (adjusted odds ratio (aOR) 3.57; 95% confidence interval (CI) 1.82
      7.02); diabetes (aOR 2.45; 95% CI 1.86-3.23); hemoglobin level less than 11 g/dl
      (aOR 1.61; 95% CI 1.21-2.15); receiving anti-hypertensive agents (aOR 3.54; 95%
      CI 2.27-5.53); and statin therapy (aOR 2.73; 95% CI 2.04-3.66). The combination
      of decreased eGFR and increased proteinuria was also associated with a higher
      prevalence of CVD. CONCLUSIONS: The participants in this cohort had a lower BMI,
      higher proteinuria and lower prevalence of CVD compared with Western cohorts.
      Lower eGFR and high proteinuria were associated with CVD prevalence. Prospective
      follow up of these study patients will contribute to establishment of individual
      population-based treatment of CKD.

PMID- 23865419
TI  - Deep brain stimulation modulates nonsense-mediated RNA decay in Parkinson's
      patients leukocytes.
AB  - BACKGROUND: Nonsense-Mediated decay (NMD) selectively degrades mRNA transcripts
      that carry premature stop codons. NMD is often triggered by alternative splicing
      (AS) modifications introducing such codons. NMD plays an important regulatory
      role in brain neurons, but the in vivo dynamics of AS and NMD changes in
      neurological diseases and under treatment were scarcely explored. RESULTS: Here,
      we report exon arrays analysis of leukocyte mRNA AS events prior to and following
      Deep Brain Stimulation (DBS) neurosurgery, which efficiently improves the motor
      symptoms of Parkinson's disease (PD), the leading movement disorder, and is
      increasingly applied to treat other diseases. We also analyzed publicly available
      exon array dataset of whole blood cells from mixed early and advanced PD
      patients. Our in-house exon array dataset of leukocyte transcripts was derived
      from advanced PD patients' pre- and post-DBS stimulation and matched healthy
      control volunteers. The mixed cohort exhibited 146 AS changes in 136 transcripts
      compared to controls, including 9 NMD protein-level assessed events. In
      comparison, PD patients from our advanced cohort differed from healthy controls
      by 319 AS events in 280 transcripts, assessed as inducing 27 protein-level NMD
      events. DBS stimulation induced 254 AS events in 229 genes as compared to the pre
      DBS state including 44 NMD inductions. A short, one hour electrical stimulus
      cessation caused 234 AS changes in 125 genes compared to ON-stimulus state, 22 of
      these were assessed for NMD. Functional analysis highlighted disease-induced DNA
      damage and inflammatory control and its reversal under ON and OFF stimulus as
      well as alternative splicing in all the tested states. CONCLUSIONS: The study
      findings indicate a potential role for NMD both in PD and following electrical
      brain stimulation. Furthermore, our current observations entail future
      implications for developing therapies for PD, and for interfering with the
      impaired molecular mechanisms that underlie PD and other neurodegenerative and
      neurological disorders, as well as DBS-treatable conditions in general.

PMID- 23865420
TI  - Anesthesia management of patients undergoing hyperthermic isolated limb perfusion
      with melphalan for melanoma treatment: an analysis of 17 cases.
AB  - BACKGROUND: Hyperthermic isolated limb perfusion (HILP) is used for patients with
      intractable or extensive in-transit metastatic melanoma of the limb to deliver
      high concentrations of cytotoxic agents to the affected limb and offers a
      treatment option in a disease stage with a poor prognosis when no treatment is
      given. METHODS: In a retrospective chart review of 17 cases, we studied the
      anesthetic and hemodynamic changes during HILP and its management. RESULTS: HILP
      was well tolerated except in one case that is described herein. We present
      summary data of all cases undergoing upper and lower limb perfusion, discuss our
      current clinical practice of preoperative, perioperative and intraoperative
      patient care including the management of HILP circuit. CONCLUSION: HILP is a
      challenging procedure, and requires a team effort including the surgical team,
      anesthesia care providers, perfusionists and nurses. Intraoperatively, invasive
      hemodynamic and metabolic monitoring is indispensable to manage significant
      hemodynamic and metabolic changes due to fluid shifts and release of cytokines.

PMID- 23865422
TI  - Bithiazole correctors rescue CFTR mutants by two different mechanisms.
AB  - Better correctors are needed to repair cystic fibrosis transmembrane conductance
      regulator (CFTR) processing mutants that cause cystic fibrosis. Determining where
      the correctors bind to CFTR would aid in the development of new correctors. A
      recent study reported that the second nucleotide-binding domain (NBD2) was
      involved in binding of bithiazole correctors. Here, we show that bithiazole
      correctors could also rescue CFTR mutants that lacked NBD2. These results suggest
      that bithiazoles rescue CFTR mutants by two different mechanisms. 

PMID- 23865421
TI  - Hyperphosphatemia in patients with ESRD: assessing the current evidence linking
      outcomes with treatment adherence.
AB  - In recent years, the imbalance in phosphate homeostasis in patients with end
      stage renal disease (ESRD) has been the subject of much research. It appears
      that, while hyperphosphatemia may be a tangible indicator of deteriorating kidney
      function, lack of phosphate homeostasis may also be associated with the increased
      risk of cardiovascular events and mortality that has become a hallmark of ESRD.
      The need to maintain phosphorus concentrations within a recommended range is
      reflected in evidence-based guidelines. However, these do not reflect serum
      phosphorus concentrations achieved by most patients in clinical practice. Given
      this discrepancy, it is important to consider ways in which dietary restriction
      of phosphorus intake and, in particular, use of phosphate binders in patients
      with ESRD can be made more effective. Poor adherence is common in patients with
      ESRD and has been associated with inadequate control of serum phosphorus
      concentrations. Studies indicate that, among other factors, major reasons for
      poor adherence to phosphate binder therapy include high pill burden and patients'
      lack of understanding of their condition and its treatment. This review examines
      available evidence, seeking to understand fully the reasons underlying poor
      adherence in patients with ESRD and consider possible strategies for improving
      adherence in clinical practice. 

PMID- 23865423
TI  - Activities of Apiaceae essential oils against armyworm, Pseudaletia unipuncta
      (Lepidoptera: Noctuidae).
AB  - Essential oils (EOs) from four Apiaceae species and 11 pure compounds were
      evaluated for their antifeedant, growth inhibitory, and insecticidal activities
      against Pseudaletia unipuncta (Lepidoptera: Noctuidae) fourth-instar larvae. EOs
      from Foeniculum vulgare subsp. vulgare var. vulgare, Anethum graveolens ,
      Petroselinum crispum , and Cuminum cyminum were characterized by gas
      chromatography (GC) and mass spectrometry. Anti-insect activity varied according
      to plant specie/composition, type, and exposure period. EOs from P. crispum and
      A. graveolens fruits, trans-anethole and cuminaldehyde, exerted acute effects on
      larvae feeding and growth (FDI and GI > 70%). A. graveolens , C. cyminum , and F.
      vulgare EOs and some of their constituents were effective by fumigation (>= 80%).
      Satisfactory contact toxicities (>70%) were observed for five compounds and all
      EOs, except F. vulgare EOs, when tested by the filter paper impregnation method.
      For the most active EOs/compounds, dose-dependent toxicity was determined and
      inverse relationships of LC50 with time were established.

PMID- 23865424
TI  - SunShot solar power reduces costs and uncertainty in future low-carbon
      electricity systems.
AB  - The United States Department of Energy's SunShot Initiative has set cost
      reduction targets of $1/watt for central-station solar technologies. We use
      SWITCH, a high-resolution electricity system planning model, to study the
      implications of achieving these targets for technology deployment and electricity
      costs in western North America, focusing on scenarios limiting carbon emissions
      to 80% below 1990 levels by 2050. We find that achieving the SunShot target for
      solar photovoltaics would allow this technology to provide more than a third of
      electric power in the region, displacing natural gas in the medium term and
      reducing the need for nuclear and carbon capture and sequestration (CCS)
      technologies, which face technological and cost uncertainties, by 2050. We
      demonstrate that a diverse portfolio of technological options can help integrate
      high levels of solar generation successfully and cost-effectively. The deployment
      of GW-scale storage plays a central role in facilitating solar deployment and the
      availability of flexible loads could increase the solar penetration level
      further. In the scenarios investigated, achieving the SunShot target can
      substantially mitigate the cost of implementing a carbon cap, decreasing power
      costs by up to 14% and saving up to $20 billion ($2010) annually by 2050 relative
      to scenarios with Reference solar costs. 

PMID- 23865425
TI  - The emerging role of connexin 43 in testis pathogenesis.
AB  - Direct intercellular communication is mediated by gap junctions and their
      constitutive proteins, the connexins, which are organized in a hexameric
      arrangement forming a channel between adjacent cells. Connexins are essential for
      cell homeostasis and are also involved in many physiological processes such as
      cell growth, differentiation and death. Spermatogenesis is a sophisticated model
      of germ cell proliferation, differentiation, survival and apoptosis, in which one
      connexin isoform, connexin 43, plays an essential role as evidenced by the
      targeted genetic deletion of Cx43 gene. A controlled balance of germ cell growth
      is a prerequisite to maintain either normal level of spermatozoa necessary for
      fertility and/or to limit an uncontrolled and anarchic germ cell proliferation, a
      major risk for germ cell tumor cell development. In the present review, we
      highlight the emerging role of connexins in testis pathogenesis, specifically in
      two intimately interconnected human testicular diseases: azoospermia with
      impaired spermatogenesis and testicular germ cell tumors, whose incidence
      increased during the last decades. This review proposes the gap junction protein
      connexin 43 as a new potential cancer diagnostic and prognostic marker, as well
      as a promising therapeutic target for testicular diseases. 

PMID- 23865426
TI  - Modulation of neutrophil development and homeostasis.
AB  - Neutrophils are highly motile phagocytic cells that constitute the first line of
      defense of the innate immune system. Unlike the other innate immune cells, mature
      neutrophils fully equipped with an armory of granules are short lived cells which
      are differentiated and programmed from hematopoietic stem cells in the bone
      marrow. In blood, mature or nearly mature cells are devoid of proliferative
      potential. While the killing mechanisms of neutrophils have been the research
      focus in the past, attention was then directed toward granulocytopoiesis by the
      recent studies about the specific functional states and exact regulatory
      mechanisms in neutrophil development and homeostasis. Here, we focus on the
      recent findings regarding the mechanisms that control the generation and
      homeostasis of neutrophils. 

PMID- 23865428
TI  - Matrix metalloproteinase inhibition in atherosclerosis and stroke.
AB  - Matrix metalloproteinases (MMPs) are a family of tightly regulated, zinc
      dependent proteases that degrade extracellular matrix (ECM), cell surface, and
      intracellular proteins. Vascular remodeling, whether as a function of normal
      physiology or as a consequence of a myriad of pathological processes, requires
      degradation of the ECM. Thus, the expression and activity of many MMPs are up
      regulated in numerous conditions affecting the vasculature and often exacerbate
      vascular dysfunction. A growing body of evidence supports the rationale of using
      MMP inhibitors for the treatment of cardiovascular diseases, stroke, and chronic
      vascular dementia. This manuscript will examine promising targets for MMP
      inhibition in atherosclerosis and stroke, reviewing findings in preclinical
      animal models and human patient studies. Strategies for MMP inhibition have
      progressed beyond chelating the catalytic zinc to functional blocking antibodies
      and peptides that target either the active site or exosites of the enzyme. While
      the inhibition of MMP activity presents a rational therapeutic avenue, the
      multiplicity of roles for MMPs and the non-selective nature of MMP inhibitors
      that cause unintended side-effects hinder full realization of MMP inhibition as
      therapy for vascular disease. For optimal therapeutic effects to be realized,
      specific targets for MMP inhibition in these pathologies must first be identified
      and then attacked by potent and selective agents during the most appropriate
      timepoint. 

PMID- 23865429
TI  - Towards more successful gene therapy clinical trials for beta-thalassemia.
AB  - beta-thalassemias constitute hereditary blood disorders characterized by reduced
      or absence of beta-globin synthesis resulting in mild to severe anemia, depending
      on the genotype. More than 200 mutations in the beta-globin gene are responsible
      for their specific features leading to a very heterogeneous phenotype. Current
      therapies for beta-thalassemia include blood transfusions, usually along with
      iron chelation and in selected cases with bone marrow transplantation (BMT) of
      HLA-matched hematopoietic stem cells (HSCs). However, these approaches are
      limited by factors, such as iron overload and donor availability, respectively.
      Since 2000, when globin lentiviral vectors (LVs) were first successfully tested
      for transfer efficiency of the therapeutic transgene, which led to disease
      amelioration in murine models, attention was drawn towards the improvement of
      such vectors for beta-thalassemia gene therapy. Constantly improving vector
      design and efficient HSC manipulation led recently to the first successful
      clinical trial in France, which further proved that this genetic approach can be
      curative. Furthermore, improved new efficient vectors and methods to safely
      monitor integration sites and therapeutic transgene position effects, promise a
      new era for beta-thalassemia gene therapy, with more and safer clinical trials
      yet to come. 

PMID- 23865430
TI  - Halitosis vaccines targeting FomA, a biofilm-bridging protein of fusobacteria
      nucleatum.
AB  - Halitosis (bad breath) is estimated to influence more than half of the world's
      population with varying degree of intensity. More than 85% of halitosis
      originates from oral bacterial infections. Foul-smelling breath mainly results
      from bacterial production of volatile sulfur compounds (VSCs) such as hydrogen
      sulfide and methyl mercaptan. To date, major treatments for elimination of oral
      malodor include periodontal therapy combined with antibiotics or antimicrobial
      agents, and mechanical approaches including tooth and tongue cleaning. These
      treatments may transiently reduce VSCs but carry risks of generating toxicity,
      increasing resistant strains and misbalancing the resident human flora.
      Therefore, there is a need to develop alternative therapeutic modalities for
      halitosis. Plaque biofilms are the principal source for generating VSCs which are
      originally metabolized from amino acids during co-aggregation of oral bacteria.
      Blocking the bacterial coaggregation, therefore, may prevent various biofilm
      associated oral diseases such as periodontitis and halitosis. Fusobacterium
      nucleatum (F. nucleatum), a Gram-negative anaerobe oral bacterium, is a main
      bacterial strain related to halitosis. Aggregation of F. nucleatum with other
      bacteria to form plaque biofilms in oral cavity causes bad breath. FomA, the
      major outer membrane protein of F. nucleatum, recruits other oral pathogenic
      bacteria such as Porphyromonas gingivalis (P. gingivalis) in the periodontal
      pockets. A halitosis vaccine targeting F. bacterium FomA significantly abrogates
      the enhancement of bacterial co-aggregation, biofilms, production of VSCs, and
      gum inflammation mediated by an inter-species interaction of F. nucleatum with P.
      gingivalis, which suggests FomA of F. nucleatum to be a potential target for
      development of vaccines or drugs against bacterial biofilm formation and its
      associated pathogenicities. 

PMID- 23865431
TI  - New advances in the pathogenesis and progression of barrett's esophagus.
AB  - Barrett's esophagus (BE) is a premalignant condition in the esophagus, with a
      rising incidence rate among Caucasians, and an established risk factor for the
      subsequent progression to esophageal adenocarcinoma (EAC). In contrast to the
      stratified squamous epithelium that normally lines the distal esophagus, BE is
      characterized by columnar epithelium that to some extent resembles the mucosa of
      the lower intestinal tract. The mechanism of intestinalization of the esophagus
      is still uncertain. For many years, it was postulated that either abnormal
      differentiation of resident progenitor cells in the esophagus, or
      transdifferentiation of mature esophageal keratinocytes provoked by reflux
      induced genetic alterations, resulted in the BE phenotype. However, more recent
      studies suggest that indigenous progenitor cells at the gastro-esophageal
      junction might, under unfavorable conditions such as TP63 loss or an activated
      inflammatory response, migrate to the esophagus and initiate columnar cell
      differentiation. In this review, we discuss the competing theories of the origins
      of BE, as well as the role of developmental signaling pathways such as Notch,
      Hedgehog, and Wnt/beta-catenin signaling that have been implicated in the
      molecular pathogenesis of BE and EAC. Additionally, we provide an overview of the
      mutational landscapes of BE and EAC, derived from the results of recently
      published next generation sequencing (NGS) studies. Future research should
      elucidate whether NGS on endoscopic mucosal biopsies can help in identifying BE
      patients at highest risk for EAC development, and whether some of the prevalent
      mutations are "actionable", leading to improvements in current therapeutic
      strategies for BE and EAC. 

PMID- 23865427
TI  - The p53-estrogen receptor loop in cancer.
AB  - Tumor suppressor p53 maintains genome stability by regulating diverse cellular
      functions including cell cycle arrest, apoptosis, senescence and metabolic
      homeostasis. Mutations in the p53 gene occur in almost all human cancers with a
      frequency of up to 80%. However, it is only 20% in breast cancers, 18% in
      endometrial cancers and 1.5% in cervical cancers. Estrogen receptor alpha
      (ERalpha) plays a pivotal role in hormone-dependent cancer development and the
      status of ERalpha is used for designing treatment strategy and for prognosis. A
      closer look at the cross-talk between p53 and ERalpha has revealed that their
      activities are mutually regulated. This review will summarize the current body of
      knowledge on p53, ERalpha and ERbeta in cancer. Clinical correlations between
      estrogen receptors and p53 status have also been reported. Thus, this review will
      discuss the relationship between p53 and ERs at both the molecular and clinical
      levels. 

PMID- 23865432
TI  - High-throughput ellipsometric characterization of vapor-deposited indomethacin
      glasses.
AB  - A method for the high-throughput preparation and characterization of vapor
      deposited organic glasses is presented. Depositing directly onto a substrate with
      a large temperature gradient allows many different glasses to be prepared
      simultaneously. Ellipsometry is used to characterize these glasses, allowing the
      determination of density, birefringence, and kinetic stability as a function of
      substrate temperature. For indomethacin, a model glass former, materials up to
      1.4% more dense than the liquid-cooled glass can be formed with a continuously
      tunable range of molecular orientations as determined by the birefringence. By
      comparing measurements of many properties, we observe three phenomenological
      temperature regimes. For substrate temperatures from Tg + 11 K to Tg - 8 K,
      equilibrium states are produced. Between Tg - 8 K and Tg - 31 K, the vapor
      deposited materials have the macroscopic properties expected for the equilibrium
      supercooled liquid while showing local structural anisotropy. At lower substrate
      temperatures, the properties of the vapor-deposited glasses are strongly
      influenced by kinetic factors. Different macroscopic properties are no longer
      correlated with each other in this regime, allowing unusual combinations of
      properties. 

PMID- 23865433
TI  - Dinitrogen reduction by a chromium(0) complex supported by a 16-membered
      phosphorus macrocycle.
AB  - We report a rare example of a Cr-N2 complex supported by a 16-membered phosphorus
      macrocycle containing pendant amine bases. Reactivity with acid afforded
      hydrazinium and ammonium, representing the first example of N2 reduction by a Cr
      N2 complex. Computational analysis examined the thermodynamically favored
      protonation steps of N2 reduction with Cr leading to the formation of hydrazine. 

PMID- 23865434
TI  - Hypervalent iodine catalyzed generation of nitrile oxides from oximes and their
      cycloaddition with alkenes or alkynes.
AB  - Hypervalent iodine catalyzed oxidation of aldoximes using oxone as a terminal
      oxidant generates nitrile oxides, which react with alkenes and alkynes to give
      the corresponding isoxazolines and isoxazoles in moderate to good yields. This
      reaction involves active hypervalent iodine species formed in situ from catalytic
      iodoarene and oxone in the presence of hexafluoroisopropanol in aqueous methanol
      solution. 

PMID- 23865435
TI  - Renal function, calcium regulation, and time to hospitalization of patients with
      chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease is associated with disruption of the endocrine
      system that distorts the balance between calcitriol, calcium, phosphate and
      parathyroid hormone in the calcium regulation system. This can lead to
      calcification of the arterial tree and increased risk of cardiovascular disease
      and death. In this study we develop a health metric, based on biomarkers involved
      in the calcium regulation system, for use in identifying patients at high risk
      for future high-cost complications. METHODS: This study is a retrospective
      observational study involving a secondary analysis of data from the kidney
      disease registry of a regional managed care organization. Chronic kidney disease
      patients in the registry from November 2007 through November 2011 with a complete
      set of observations of estimated glomerular filtration rate, calcitriol, albumin,
      free calcium, phosphate, and parathyroid hormone were included in the study (n =
      284). Weibull regression model was used to identify the most significant lab
      tests in predicting "waiting time to hospitalization". A multivariate linear path
      model was then constructed to investigate direct and indirect effects of the
      biomarkers on this outcome. RESULTS: The results showed negative significant
      direct effects of phosphate and parathyroid hormone on "waiting time to
      hospitalization". Base on this result, the risk of hospitalization increases
      16.8% for each 0.55 mg/dl increase in phosphate level and 13.5% for each 0.467
      increase in the natural logarithm of parathyroid hormone. Positive indirect
      effects of calcitriol surrogate (calcidiol), free calcium, albumin and estimated
      glomerular filtration rate were observed but were relatively small in magnitude.
      CONCLUSION: Variables involved in the calcium regulation system should be
      included in future efforts to develop a quality of care index for Chronic Kidney
      disease patients.

PMID- 23865436
TI  - Dabigatran for thromboprophylaxis after robotic assisted laparoscopic
      prostatectomy: retrospective analysis of safety profile and effect on blood
      coagulation.
AB  - OBJECTIVE: The aims of this study were to analyse the efficacy and safety of
      orally administered dabigatran in prostate cancer patients who have undergone
      robotic assisted laparoscopic prostatectomy (RALP) and to analyse the effects of
      RALP on selected markers of coagulation activity. MATERIAL AND METHODS: Data were
      collected prospectively on the first 400 patients who underwent RALP at Helsinki
      University Central Hospital between 2009 and 2011. As thromboprophylaxis,
      intermittent compression devices were used in association with anaesthesia.
      Dalteparin sodium at 2500 IU was administered on the preoperative evening and at
      5000 IU daily until discharge. Then patients were prescribed 220 mg dabigatran
      etexilate once daily for the next 15 days. Bleeding and thromboembolic
      complications were recorded. A set of routine coagulation analyses was undertaken
      in 61 patients preoperatively, on the first, second and eight postoperative days.
      RESULTS: One patient with obesity- and cancer-related risk factors developed
      venous thromboembolism 18 days after the operation. Nine patients (2.3%) had
      postoperative blood loss or bleeds, eight patients required blood transfusions
      and three underwent reoperation before dabigatran administration. Increased
      fibrinogen, factor VIII, d-dimer and thrombocytosis were observed
      postoperatively, reflecting coagulation activity. CONCLUSIONS: RALP activates
      coagulation, and thromboprophylaxis for high-risk patients even after minimally
      invasive surgery may be beneficial. Orally administered dabigatran after
      discharge from hospital appears safe for venous thromboembolism prophylaxis after
      RALP.

PMID- 23865437
TI  - Postmortem evaluation of 435 cases of intracranial neoplasia in dogs and
      relationship of neoplasm with breed, age, and body weight.
AB  - BACKGROUND: Intracranial neoplasia of dogs is frequently encountered in
      veterinary medicine, but large-scale studies on prevalence are lacking.
      OBJECTIVES: To determine the prevalence of intracranial neoplasia in a large
      population of dogs examined postmortem and the relationship between breed, age,
      and weight with the presence of primary intracranial neoplasms. ANIMALS: All dogs
      that underwent postmortem examination from 1986 through 2010 (n = 9,574),
      including dogs with a histopathologic diagnosis of primary (n = 227) and
      secondary (n = 208) intracranial neoplasia. METHODS: Retrospective evaluation of
      medical records from 1986 through 2010. RESULTS: Overall prevalence of
      intracranial neoplasia in this study's population of dogs was 4.5%. A
      statistically significant higher prevalence of primary intracranial neoplasms was
      found in dogs with increasing age and body weights. Dogs >=15 kg had an increased
      risk of meningioma (odds ratio 2.3) when compared to dogs <15 kg. The Boxer,
      Boston Terrier, Golden Retriever, French Bulldog, and Rat Terrier had a
      significantly increased risk of primary intracranial neoplasms while the Cocker
      Spaniel and Doberman Pinscher showed a significantly decreased risk of primary
      intracranial neoplasms. CONCLUSIONS AND CLINICAL IMPORTANCE: Intracranial
      neoplasia in dogs might be more common than previous estimates. The study
      suggests that primary intracranial neoplasia should be a strong differential in
      older and larger breed dogs presenting with signs of nontraumatic intracranial
      disease. Specific breeds have been identified with an increased risk, and others
      with a decreased risk of primary intracranial neoplasms. The results warrant
      future investigations into the role of age, size, genetics, and breed on the
      development of intracranial neoplasms.

PMID- 23865438
TI  - Background, clinical features and treatment of attention deficit hyperactivity
      disorder in children.
AB  - INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is an early onset,
      clinically heterogeneous, complex neurobiological disorder, defined by symptoms
      of inattention and hyperactivity/impulsivity and has been associated with a broad
      range of impairments for those affected. Additionally, ADHD in children and
      adolescents is frequently associated with psychiatric comorbidities. This review
      provides an overview of the epidemiology, neurobiology, genetics, diagnosis and
      most recent pharmacological approaches for treatment with a focus on safety and
      efficacy and describes the use of medications used to treat ADHD in special
      populations. AREAS COVERED: PubMed, Cochrane database, Essential Evidence and
      Uptodate were searched for relevant articles about stimulant and non-stimulant
      pharmacological approaches in ADHD. EXPERT OPINION: Data supporting the safety
      and efficacy of both stimulant and non-stimulant formulations have significantly
      grown over the past decade and more efforts are being made to tailor medications
      to the needs of the patients and their families. Pharmacogenomics research is
      evolving, but predictors of treatment response and side effects remain largely
      unknown. Other unmet clinical needs include long-term follow-up studies of the
      safety and efficacy of medications for those with ADHD alone, or with
      comorbidities and in special populations including preschoolers.

PMID- 23865439
TI  - Development and Preliminary Evaluation of a New Real-Time RT-PCR Assay For
      Detection of Peste des petits Ruminants Virus Genome.
AB  - A duplex real-time reverse transcription-polymerase chain reaction (qRT-PCR)
      assay was developed for a simple and rapid diagnosis of Peste des petits
      ruminants (PPR). qRT-PCR primers and TaqMan probe were designed on a conserved
      region of nucleocapsid protein (Np) of PPR virus (PPRV) genome. An in vitro
      transcript of the target region was constructed and tested to determine
      analytical sensitivity. Commercial heterologous Armored RNA((r)) was used as an
      internal positive control (IPC) for either RNA isolation or RT-PCR steps. The
      detection limit of the newly designed duplex real-time RT-PCR (qRT-PCR PPR_Np)
      was approximately 20 copies/MUl with a 95% probability. No amplification signals
      were recorded when the qRT-PCR PPR_Np was applied to viruses closely related or
      clinically similar to PPRV- or to PPR-negative blood samples. A preliminary
      evaluation of the diagnostic performance was carried out by testing a group of 43
      clinical specimens collected from distinct geographic areas of Africa and Middle
      East. qRT-PCR PPR_Np showed higher sensitivity than the conventional gel-based RT
      PCR assays, which have been used as reference standards. Internal positive
      control made it possible to identify the occurrence of 5 false-negative results
      caused by the amplification failure, thus improving the accuracy of PPRV
      detection.

PMID- 23865440
TI  - Role of inactivated influenza vaccine in regulation of autoimmune processes in
      experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is characterized by appearance of
      anti-myelin autoantibodies in the blood and with the increased expression of MHC
      (major histocompatibility complex) class I and II antigens in the brain tissue.
      Although there is an evidence of possible linkage between influenza vaccination
      and development of autoimmune processes, the precise mechanisms of action of this
      vaccine on EAE-induction is still unclear. In this study, effects of influenza
      vaccine on clinical sign, antimyelin antibody titer in the blood by ELISA test
      and expression of MHC class I and II molecules immunohistochemistry were examined
      in the brain of C57BL mice with EAE. EAE was induced by MOG 35-55 protein in 16
      of 32 mice. Influenza split vaccine was administered to eight MOG-induced EAE
      mice and to eight previously nontreated mice. A significant increase of anti
      influenza antibody was detected in vaccinated mice compared to nontreated mice.
      Also, significant increase of antimyelin antibodies was detected in mice with EAE
      compared to vaccinated group without EAE and control group, respectively. In EAE
      influenza vaccinated mice, a mild but not significant increase of antimyelin
      antibodies was detected, compared to EAE mice. High expression of MHC-II and mild
      expression of MHC-I were detected in the brain of mice with EAE. No expressions
      were detected in vaccinated and normal intact brains. Similar staining was found
      between EAE-vaccinated and EAE group in both MHC-I and MHC-II expression. The
      results obtained show that influenza vaccine has no significant influence on EAE
      induction and severity of autoimmune processes.

PMID- 23865441
TI  - A comparative study on the effectiveness of losartan/hydrochlorothiazide and
      telmisartan/hydrochlorothiazide in patients with hypertension.
AB  - PURPOSE: Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan
      (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been
      studied in hypertensive patients in comparison with those of a low-dose HCTZ with
      telmisartan (TEL). METHOD: Fifty-nine hypertensive patients were allocated to a
      combination therapy with either losartan (50 mg/day)/HCTZ (12.5 mg/day) (LOS +
      HCTZ group: n = 37) or telmisartan (40 mg/day)/HCTZ (12.5 mg/day) (TEL + HCTZ
      group: n = 22), respectively. Before and 1 year after the treatment, blood
      pressure and biochemical parameters of blood and urine were evaluated. RESULTS:
      Both systolic and diastolic blood pressures significantly decreased in two
      groups, without any statistical differences among them. LOS + HCTZ caused no
      changes in the serum UA level or the ratio of UA clearance to creatinine
      clearance (CUA/Ccr), whereas TEL + HCTZ significantly increased the serum UA
      level and reduced CUA/Ccr. LOS + HCTZ did not influence CUA/Ccr in patients with
      their serum UA below 5.4 mg/dl, while LOS + HCTZ significantly increased CUA/Ccr
      in patients with their serum UA above 5.5 mg/dl. TEL + HCTZ significantly reduced
      CUA/Ccr in patients with their serum UA below and above 5.4 mg/dl to increase
      serum UA level significantly. Neither combination therapies caused any changes in
      fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level
      above 5.4 mg/dl, TEL + HCTZ increased HOMA-R, whereas LOS + HCTZ did not.
      CONCLUSIONS: LOS + HCTZ did not influence UA metabolism as well as glucose
      metabolism, likely because of inhibitory action of losartan on URAT1, although
      TEL + HCTZ were accompanied with impairment of the UA metabolism and glucose
      metabolism.

PMID- 23865442
TI  - Perioperative anxiety and postoperative pain in children and adolescents
      undergoing elective surgical procedures: a quantitative systematic review.
AB  - AIMS: To examine the relationship between perioperative anxiety and postoperative
      pain in children and adolescents undergoing elective surgical procedures and the
      differences in children's perioperative anxiety and postoperative pain among
      subgroups of demographics. BACKGROUND: While anxiety and pain are regarded as two
      common problems experienced by children and adolescents perioperatively and the
      relationship between them has been reported in previous studies, there has been
      no review paper examining this phenomenon. DESIGN: A quantitative systematic
      review. DATA SOURCES: Nine electronic databases were searched for studies
      published in English from the inception date of the databases to December 2010,
      using various combinations of search terms of 'adolescents', 'anxiety', 'child',
      'pain', 'surgery' and 'correlation/relationship'. REVIEW METHODS: Using the
      Joanna Briggs Institute's comprehensive systematic review strategies, relevant
      studies were independently appraised and extracted by two reviewers using the
      standardized critical appraisal instruments and data extraction tool from Joanna
      Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument.
      RESULTS: Ten studies were included in this review from 943 studies initially
      retrieved. Children and adolescents who had higher level of perioperative anxiety
      experienced a higher level of postoperative pain. Inconclusive evidence was found
      regarding differences of perioperative anxiety and postoperative pain between
      demographic subgroups of gender, age and past surgical experience. CONCLUSION:
      Results of this review inform healthcare providers of the role perioperative
      anxiety plays on children's and adolescents' postoperative pain and indicate the
      need to use interventions to reduce perioperative anxiety and, therefore,
      optimize their postoperative pain management during the perioperative period.

PMID- 23865443
TI  - Synthesis, crystal structure and catalytic behavior of homo- and heteronuclear
      coordination polymers [M(tdc)(bpy)] (M2+ = Fe2+, Co2+, Zn2+, Cd2+; tdc2- = 2,5
      thiophenedicarboxylate).
AB  - A series of isostructural 3D coordination polymers (3)infinity[M(tdc)(bpy)]
      (M(2+) = Zn(2+), Cd(2+), Co(2+), Fe(2+); tdc(2-) = 2,5-thiophenedicarboxylate;
      bpy = 4,4'-bipyridine) was synthesized and characterized by X-ray diffraction,
      thermal analysis, and gas adsorption measurements. The materials show high
      thermal stability up to approximately 400  degrees C and a solvent induced phase
      transition. Single crystal X-ray structure determination was successfully
      performed for all compounds after the phase transition. In the zinc-based
      coordination polymer, various amounts of a second type of metal ions such as
      Co(2+) or Fe(2+) could be incorporated. Furthermore, the catalytic behavior of
      the homo- and heteronuclear 3D coordination polymers in an oxidation model
      reaction was investigated. 

PMID- 23865444
TI  - Application of laws, policies, and guidance from the United States and Canada to
      the regulation of food and feed derived from genetically modified crops:
      interpretation of composition data.
AB  - With the development of recombinant DNA techniques for genetically modifying
      plants to exhibit beneficial traits, laws and regulations were adopted to ensure
      the safety of food and feed derived from such plants. This paper focuses on the
      regulation of genetically modified (GM) plants in Canada and the United States,
      with emphasis on the results of the compositional analysis routinely utilized as
      an indicator of possible unintended effects resulting from genetic modification.
      This work discusses the mandate of Health Canada and the Canadian Food Inspection
      Agency as well as the U.S. Food and Drug Administration's approach to regulating
      food and feed derived from GM plants. This work also addresses how publications
      by the Organisation for Economic Co-operation and Development and Codex
      Alimentarius fit, particularly with defining the importance and purpose of
      compositional analysis. The importance of study design, selection of comparators,
      use of literature, and commercial variety reference values is also discussed. 

PMID- 23865445
TI  - The dynamic observation of plasma concentration of antimicrobial agents during
      balanced ultrafiltration in vitro.
AB  - Routine perioperative intravenous antimicrobial agents are administered as
      surgical prophylaxis. However, whether balanced ultrafiltration during
      extracorporeal circulation has substantial effect on the concentration of
      antimicrobial agents remains unclear. The concentrations of antimicrobial agents
      in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal
      circulation model. Extracorporeal circulation consisted of cardiotomy reservoir,
      membrane oxygenator, and pediatric arterial line filter. A hemoconcentrator was
      placed between the arterial purge line and oxygenator venous reservoir. Fresh
      donor human whole blood was added into the circuit and mixed with Ringer's
      solution to obtain a final hematocrit of 24-28%. Two kinds of antimicrobial
      agents, cefotiam (320 mg) and cefmetazole (160 mg), were bolus added into the
      circuit. After 30 min of extracorporeal circulation, zero-balanced
      ultrafiltration was initiated and arterial line pressure was maintained at
      approximately 100 mm Hg with a Hoffman clamp. The rate of ultrafiltration (12
      mL/min) was controlled by ultrafiltrate outlet pressure. An identical volume of
      Plasmalyte A was dripped into the circuit to maintain stable hematocrit during 45
      min of experiment. Plasma and ultrafiltrate samples were drawn every 5 min, and
      concentrations of antimicrobial agents (including cefotiam and cefmetazole) were
      measured with high performance liquid chromatography. Both antimicrobial agents
      were detected in ultrafiltrate, demonstrating hemoconcentration may remove
      antimicrobial agents. The concentrations of plasma antimicrobial agents decreased
      linearly with the increase of ultrafiltrate volume. At end of balanced
      ultrafiltration, the concentration of plasma cefotiam was 104.96 +/- 44.36 mg/L,
      which is about 44.38% +/- 7.42% of the initial concentration (238.95 +/- 101.12
      mg/L) (P < 0.001); the concentration of plasma cefmetazole decreased linearly to
      25.76 +/- 14.78 mg/L, which is about 49.69% +/- 10.49% of the initial
      concentration (51.49 +/- 28.03 mg/L) (P < 0.001). The total amount of cefotiam in
      ultrafiltrate is 27.16% +/- 12.17% of the total dose administered, whereas
      cefmetazole in ultrafiltrate is 7.74% +/- 4.17%. Balanced ultrafiltration may
      remove antimicrobial agents from plasma and has a prominent influence on plasma
      concentration of antimicrobial agent. The strategy of surgical prophylaxis should
      consider this unique technique during extracorporeal circulation. 

PMID- 23865446
TI  - Corona of glomerular vessels: a diagnostic marker of hyperkeratotic Bowen's
      disease.

PMID- 23865447
TI  - Treatment benefit and treatment harm rate to characterize heterogeneity in
      treatment effect.
AB  - It is well recognized that the conventional summary of treatment effect by
      averaging across individual patients has its limitation in ignoring the
      heterogeneous responses to the treatment in the target population. However, there
      are few alternative metrics in the literature that are designed to capture such
      heterogeneity. We propose the concept of treatment benefit rate (TBR) and
      treatment harm rate (THR) that characterize both the overall treatment effect and
      the magnitude of heterogeneity. We discuss a method to estimate TBR and THR that
      easily incorporates a sensitivity analysis scheme, and illustrate the idea
      through analysis of a randomized trial that evaluates the implantable
      cardioverter-defibrillator (ICD) in reducing mortality. A simulation study is
      presented to assess the performance of the proposed method. 

PMID- 23865448
TI  - Effect of pretreatment with dehulling and microwaving on the flavor
      characteristics of cold-pressed rapeseed oil by GC-MS-PCA and electronic nose
      discrimination.
AB  - Raw and dehulled rapeseeds were treated with microwave energy (800 W) from 1 to 8
      min with 1-min intervals at a frequency of 2450 MHz to investigate the influence
      of microwaving and dehulling pretreatment on the flavor characteristics of
      rapeseed oil extracted by pressing. Headspace solid phase microextraction was
      used to isolate the volatile compounds of rapeseed oil, which were then
      identified by gas chromatography-mass spectrometry analysis. The results
      indicated that microwave and dehulling pretreatment of rapeseed can significantly
      influence the kinds and content of volatile compounds. The key flavor compounds
      in rapeseed oil were oxidized volatiles, heterocyclic compounds, and degradation
      products of glucosinolates. A pungent compound, 4-isothiocyanato-1-butene, was
      reduced by 97% in rapeseed treated for 3 min with microwaves energy when compared
      to the rapeseed oil without any treatment. The pyrazine compounds in the oil
      appeared after 6 min of microwave pretreatment and give a pleasant roasting
      flavor when compared to crude oils. Principal component analysis was able to
      differentiate between oils obtained using 4 pretreatment processes based on
      volatile compounds and electronic nose. The results showed that dehulling
      pretreatment could improve the flavor, yet microwaving had a greater effect on
      the flavor of rapeseed oils. 

PMID- 23865449
TI  - Solid lipid dispersions: potential delivery system for functional ingredients in
      foods.
AB  - Structured solid lipid (SL) systems have the advantages of long-term physical
      stability, low surfactant concentrations, and may exhibit controlled release of
      active ingredients. In this research work, the potential use of high-melting SLs
      for the production of the above structured SL carrier systems was investigated.
      Dispersions containing either SL or blend of solid lipid and oil (SL+O) were
      produced by a hot melt high-pressure homogenization method. Experiments involved
      the use of 3 different SLs for the disperse phase: stearic acid, candelilla wax
      and carnauba wax. Sunflower oil was incorporated in the disperse phase for the
      production of the dispersions containing lipid and oil. In order to evaluate the
      practical aspects of structured particles, analytical techniques were used
      including: static light scattering to measure particle sizes, transmission
      electron microscopy (TEM) for investigating particle morphology and differential
      scanning calorimetry (DSC) to investigate the crystallization behavior of lipids
      in bulk and in dispersions. Results showed different mean particle sizes
      depending on the type of lipid used in the disperse phase. Particle sizes for the
      3 lipids were: stearic acid (SL: 195 +/- 2.5 nm; SL+O: 138 +/- 6.0 nm);
      candelilla wax (SL: 178 +/- 1.7 nm; SL+O: 144 +/- 0.6 nm); carnauba wax (SL: 303
      +/- 1.5 nm; SL+O: 295 +/- 5.0 nm). TEM results gave an insight into the practical
      morphology, showing plate-like and needle-like structures. DSC investigations
      also revealed that SL dispersions melted and crystallized at lower temperatures
      than the bulk. This decrease can be explained by the small particle sizes of the
      dispersion, the high-specific surface area, and the presence of a surfactant. 

PMID- 23865451
TI  - Inhibition of bacterial and filamentous fungal growth in high moisture,
      nonsterile corn with intermittent pumping of trans-2-hexenal vapor.
AB  - Trans-2-hexenal (T2H), a plant-produced aldehyde, was intermittently pumped over
      a 7 d period into a small, bench top model of stored corn (nonsterile, moisture
      content about 23%). Naturally occurring bacteria and fungi, including added
      Aspergillus flavus, grew rapidly on corn not treated with T2H vapor. However,
      intermittently pumped T2H (30 min per 2 h or 30 min per 12 h) significantly
      reduced bacterial and fungal viable populations, with nearly 100% fungal
      viability loss observed after either (1) one day of pumping at the 30 min per 2 h
      rate or (2) pumping cycles of 30 min per 12 h period over the initial 48 to 72 h
      of incubation. Data suggest that short-term intermittent fumigation of stored
      corn with T2H could prevent growth of bacteria and mycotoxigenic fungi such as A.
      flavus. 

PMID- 23865452
TI  - Quality properties, fatty acids, and biogenic amines profile of fresh tilapia
      stored in ice.
AB  - This work determines quality properties and fatty acids content of Nile tilapia
      (Oreochromis niloticus) stored in ice for 21 d. The quality properties consist of
      thiobarbituic acid (TBA), total volatile basic nitrogen (TVB-N), trimethylamine
      (TMA), and microbiological analysis (total viable count (TVC), total coliform,
      Salmonella and Staphylococcus aureus) and determination of biogenic amines
      content (histamine, cadaverine, putrescine, spermine, spermidine, 2
      phenylethylamine, agmatine, tyramine, and ammonia). Moreover, the fat, moisture,
      and ash composition as well as fatty acids profile have also been analyzed. The
      TBA, TVB-N, and biogenic amines analysis showed rather low levels of spoilage
      even after 21 d of storage. The microbiological analysis, however, showed that
      tilapia was unsuitable for consumption after just 10 d. The fat, ash, moisture,
      and fatty acids profile analysis showed that tilapia is not a good source of n-3
      fatty acids. The research indicated that the microbiological analysis was the
      best method to establish spoilage of tilapia stored in ice, of all analytical
      methods performed in this study. 

PMID- 23865453
TI  - Intermolecular interactions and aggregation of fac-tris(2-phenylpyridinato
      C2,N)iridium(III) in nonpolar solvents.
AB  - The intermolecular interaction and aggregation of the neutral complex fac-tris(2
      phenylpyridinato-C(2),N)iridium(III) (fac-Ir(ppy)3) in solution was investigated.
      Intermolecular interactions were found to effectively decrease the luminescence
      lifetime via self-quenching with increasing fac-Ir(ppy)3 concentrations. A Stern
      Volmer plot for quenching in acetonitrile was linear, due to bimolecular self
      quenching, but curved in toluene as the result of excimer formation. (1)H NMR
      spectra demonstrated a monomer-aggregate equilibrium which resulted in spectral
      shifts depending on solvent polarity. X-ray crystallography provided structural
      information concerning the aggregate, which is based on a tetramer consisting of
      two Delta-fac-Ir(ppy)3-Lambda-fac-Ir(ppy)3 pairs. Offset pi-pi stacking of ppy
      ligands and electrostatic dipole-dipole interactions between complex molecules
      play an important role in the formation of these molecular pairs. 

PMID- 23865454
TI  - Selenocysteine confers resistance to inactivation by oxidation in thioredoxin
      reductase: comparison of selenium and sulfur enzymes.
AB  - Mammalian thioredoxin reductase (TR) is a selenocysteine (Sec)-containing
      homodimeric pyridine nucleotide oxidoreductase which catalyzes the reduction of
      oxidized thioredoxin. We have previously demonstrated the full-length
      mitochondrial mammalian TR (mTR3) enzyme to be resistant to inactivation from
      exposure to 50 mM H2O2. Because a Sec residue oxidizes more rapidly than a
      cysteine (Cys) residue, it has been previously thought that Sec-containing
      enzymes are "sensitive to oxidation" compared to Cys-orthologues. Here we show
      for the first time a direct comparison of the abilities of Sec-containing mTR3
      and the Cys-orthologue from D. melanogaster (DmTR) to resist inactivation by
      oxidation from a variety of oxidants including H2O2, hydroxyl radical,
      peroxynitrite, hypochlorous acid, hypobromous acid, and hypothiocyanous acid. The
      results show that the Sec-containing TR is far superior to the Cys-orthologue TR
      in resisting inactivation by oxidation. To further test our hypothesis that the
      use of Sec confers strong resistance to inactivation by oxidation, we constructed
      a chimeric enzyme in which we replaced the active site Cys nucleophile of DmTR
      with a Sec residue using semisynthesis. The chimeric Sec-containing enzyme has
      similar ability to resist inactivation by oxidation as the wild type Sec
      containing TR from mouse mitochondria. The use of Sec in the chimeric enzyme
      "rescued" the enzyme from oxidant-induced inactivation for all of the oxidants
      tested in this study, in direct contrast to previous understanding. We discuss
      two possibilities for this rescue effect from inactivation under identical
      conditions of oxidative stress: (i) Sec resists overoxidation and inactivation,
      whereas a Cys residue can be permanently overoxidized to the sulfinic acid form,
      and (ii) Sec protects the body of the enzyme from harmful oxidation by allowing
      the enzyme to metabolize (turnover) various oxidants much better than a Cys
      containing TR. 

PMID- 23865455
TI  - Clinal variation in a brown lemur (Eulemur spp.) hybrid zone: combining
      morphological, genetic and climatic data to examine stability.
AB  - Studies of hybrid zones can inform our understanding of reproductive isolation
      and speciation. Two species of brown lemur (Eulemur rufifrons and E. cinereiceps)
      form an apparently stable hybrid zone in the Andringitra region of southeastern
      Madagascar. The aim of this study was to identify factors that contribute to this
      stability. We sampled animals at 11 sites along a 90-km transect through the
      hybrid zone and examined variation in 26 microsatellites, the D-loop region of
      mitochondrial DNA, six pelage and nine morphological traits; we also included
      samples collected in more distant allopatric sites. Clines in these traits were
      noncoincident, and there was no increase in either inbreeding coefficients or
      linkage disequilibrium at the centre of the zone. These results could suggest
      that the hybrid zone is maintained by weak selection against hybrids, conforming
      to either the tension zone or geographical selection-gradient model. However, a
      closer examination of clines in pelage and microsatellites indicates that these
      clines are not sigmoid or stepped in shape but instead plateau at their centre.
      Sites within the hybrid zone also occur in a distinct habitat, characterized by
      greater seasonality in precipitation and lower seasonality in temperature.
      Together, these findings suggest that the hybrid zone may follow the bounded
      superiority model, with exogenous selection favouring hybrids within the
      transitional zone. These findings are noteworthy, as examples supporting the
      bounded superiority model are rare and may indicate a process of ecologically
      driven speciation without geographical isolation.

PMID- 23865456
TI  - A survey of education and confidence level among graduating anesthesia residents
      with regard to selected peripheral nerve blocks.
AB  - BACKGROUND: As peripheral nerve blockade has increased significantly over the
      past decade, resident education and exposure to peripheral nerve blocks has also
      increased. This survey assessed the levels of exposure and confidence that
      graduating residents have with performing selected peripheral nerve blocks.
      METHODS: All program directors of ACGME-accredited anesthesiology programs in the
      USA were asked to distribute an online survey to their graduating residents.
      Information was gathered on the number and types of nerve blocks performed,
      technique(s) utilized, perceived comfort level in performing nerve blocks,
      perceived quality of regional anesthesia teaching during residency, and suggested
      areas for improvement. RESULTS: One hundred and seven residents completed the
      survey. The majority completed more than 60 nerve blocks. Femoral and
      interscalene blocks were performed most frequently, with 59% and 41% of residents
      performing more than 20 of each procedure, respectively. The least-performed
      block was the lumber plexus block, with just 9% performing 20 or more blocks.
      Most residents reported feeling "very" to "somewhat" comfortable performing the
      surveyed blocks, with the exception of the lumber plexus block, where 64% were
      "not comfortable." Overall, 78% of residents were "mostly" to "very satisfied"
      with the quality of education received during residency. CONCLUSIONS: Most of the
      respondents fulfilled the ACGME requirement and expressed satisfaction with the
      peripheral nerve block education received during residency. However, the ACGME
      requirement for 40 nerve blocks may not be adequate for some residents to feel
      comfortable in performing a full range of blocks upon graduation. Many residents
      felt that curriculums incorporating simulator training and didactic lectures
      would be the most helpful method of improving the quality of their education
      pertaining to peripheral nerve blocks.

PMID- 23865457
TI  - Serum serotonin concentration is associated with severity of myxomatous mitral
      valve disease in dogs.
AB  - BACKGROUND: The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has
      recently been suggested to play a role in the development of naturally acquired
      myxomatous mitral valve disease (MMVD) in dogs. AIM: To investigate the
      association between serum 5-HT concentration and MMVD severity in dogs, and to
      assess potential associations between serum 5-HT concentrations and dog
      characteristics, echocardiographic variables, heart rate, systolic blood
      pressure, presence of macrothrombocytosis, and plateletcrit. ANIMALS: A total of
      120 client-owned dogs. MATERIAL AND METHODS: Dogs were prospectively recruited
      and were classified by standard echocardiography into healthy (dogs of breeds
      predisposed to MMVD, but without echocardiographic evidence of the disease),
      mild, moderate, or severe MMVD groups. Serum 5-HT concentrations were analyzed
      using an ELISA. RESULTS: Dogs with severe MMVD had lower serum 5-HT
      concentrations than healthy dogs (P = .0025) and dogs with mild MMVD (P = .0011).
      Unilinear and multiple regression analyses showed that serum 5-HT concentrations
      decreased with increasing left atrial to aortic root ratio (LA/Ao), were higher
      in Cavalier King Charles Spaniel (CKCS) dogs compared to dogs of other breeds,
      and were higher in female dogs than in male dogs. The LA/Ao was the variable most
      strongly associated with serum 5-HT concentration. CONCLUSIONS AND CLINICAL
      IMPORTANCE: The finding of higher serum 5-HT concentrations in dogs of breeds
      predisposed to the early onset of MMVD (CKCS) and dogs with mild MMVD suggests
      that alterations in 5-HT signaling might play a role in progression of early
      stages of MMVD.

PMID- 23865458
TI  - The role of ion mobility spectrometry-mass spectrometry in the analysis of
      protein reference standards.
AB  - To achieve comparability of measurement results of protein amount of substance
      content between clinical laboratories, suitable reference materials are required.
      The impact on measurement comparability of potential differences in the tertiary
      and quaternary structure of protein reference standards is as yet not well
      understood. With the use of human growth hormone as a model protein, the
      potential of ion mobility spectrometry-mass spectrometry as a tool to assess
      differences in the structure of protein reference materials and their
      interactions with antibodies has been investigated here. 

PMID- 23865460
TI  - Bimetallic oxidative addition involving radical intermediates in nickel-catalyzed
      alkyl-alkyl Kumada coupling reactions.
AB  - Many nickel-based catalysts have been reported for cross-coupling reactions of
      nonactivated alkyl halides. The mechanistic understanding of these reactions is
      still primitive. Here we report a mechanistic study of alkyl-alkyl Kumada
      coupling catalyzed by a preformed nickel(II) pincer complex ([(N2N)Ni-Cl]). The
      coupling proceeds through a radical process, involving two nickel centers for the
      oxidative addition of alkyl halide. The catalysis is second-order in Grignard
      reagent, first-order in catalyst, and zero-order in alkyl halide. A transient
      species, [(N2N)Ni-alkyl(2)](alkyl(2)-MgCl), is identified as the key intermediate
      responsible for the activation of alkyl halide, the formation of which is the
      turnover-determining step of the catalysis. 

PMID- 23865459
TI  - Explicit consideration of topological and parameter uncertainty gives new
      insights into a well-established model of glycolysis.
AB  - Previous models of glycolysis in the sleeping sickness parasite Trypanosoma
      brucei assumed that the core part of glycolysis in this unicellular parasite is
      tightly compartimentalized within an organelle, the glycosome, which had
      previously been shown to contain most of the glycolytic enzymes. The glycosomes
      were assumed to be largely impermeable, and exchange of metabolites between the
      cytosol and the glycosome was assumed to be regulated by specific transporters in
      the glycosomal membrane. This tight compartmentalization was considered to be
      essential for parasite viability. Recently, size-specific metabolite pores were
      discovered in the membrane of glycosomes. These channels are proposed to allow
      smaller metabolites to diffuse across the membrane but not larger ones. In light
      of this new finding, we re-analyzed the model taking into account uncertainty
      about the topology of the metabolic system in T. brucei, as well as uncertainty
      about the values of all parameters of individual enzymatic reactions. Our
      analysis shows that these newly-discovered nonspecific pores are not necessarily
      incompatible with our current knowledge of the glycosomal metabolic system,
      provided that the known cytosolic activities of the glycosomal enzymes play an
      important role in the regulation of glycolytic fluxes and the concentration of
      metabolic intermediates of the pathway.

PMID- 23865461
TI  - Androgen ablation for low-risk prostate cancer is common among male hip fracture
      patients.
AB  - OBJECTIVE: This study aimed to evaluate the prevalence of androgen deprivation
      therapy (ADT) among male hip fracture patients with prostate cancer and to
      analyse their indications for ADT with regard to prostate cancer risk
      classification. MATERIAL AND METHODS: Tampere University Hospital records were
      screened for International Classification of Diseases, 10th revision (ICD-10)
      diagnoses S72.0-72.2 in 1998-2008 to identify hip fractures among males. Prostate
      cancer and fracture characteristics and concomitant medications were recorded.
      Fracture patients with prior prostate cancer diagnosis were compared to control
      patients from the Tampere University prostate cancer database and the risk
      factors for fracture were analysed by binary logistic regression analysis.
      RESULTS: In total, 133 patients (11.0% of hip fractures) had a prostate cancer
      diagnosis prior to fracture; of these, 111 (84.1%) had osteoporotic, 14 (10.6%)
      pathological and seven (5.3%) high-energy fractures. Furthermore, 117 (88.0%) of
      fracture patients had received ADT for their prostate cancer. The mean interval
      between castration and fracture was 5.9 years (median 4.6 years). Of the fracture
      patients with prostate cancer, 24.8% had been primarily castrated for a low-risk
      disease. In multivariate analysis, ADT was a significant risk factor for fracture
      among low [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.14-8.01, p =
      0.027], intermediate (OR 4.52, 95% CI 1.32-15.40, p = 0.016) and high-risk
      prostate cancer patients (OR 5.85, 95% CI 1.30-26.30, p = 0.021). CONCLUSIONS:
      Hormonally treated prostate cancer is a major risk factor for osteoporotic hip
      fracture in males. Nearly a quarter of the prostate cancer patients suffering a
      hip fracture had been treated by primary castration despite having low-risk
      prostate cancer, emphasizing the importance of patient selection and timing for
      ADT.

PMID- 23865462
TI  - Distinct roles of the Gcn5 histone acetyltransferase revealed during transient
      stress-induced reprogramming of the genome.
AB  - BACKGROUND: Gcn5 belongs to a family of histone acetyltransferases (HATs) that
      regulate protein function by acetylation. Gcn5 plays several different roles in
      gene transcription throughout the genome but their characterisation by classical
      mutation approaches is hampered by the high degree of apparent functional
      redundancy between HAT proteins. RESULTS: Here we utilise the reduced redundancy
      associated with the transiently high levels of genomic reprogramming during
      stress adaptation as a complementary approach to understand the functions of
      redundant protein families like HATs. We show genome-wide evidence for two
      functionally distinct roles of Gcn5. First, Gcn5 transiently re-localises to the
      ORFs of long genes during stress adaptation. Taken together with earlier
      mechanistic studies, our data suggests that Gcn5 plays a genome- wide role in
      specifically increasing the transcriptional elongation of long genes, thus
      increasing the production efficiency of complete long transcripts. Second, we
      suggest that Gcn5 transiently interacts with histones close to the transcription
      start site of the many genes that it activates during stress adaptation by
      acetylation of histone H3K18, leading to histone depletion, probably as a result
      of nucleosome loss as has been described previously. CONCLUSIONS: We show that
      stress adaptation can be used to elucidate the functions of otherwise redundant
      proteins, like Gcn5, in gene transcription. Further, we show that normalization
      of chromatin-associated protein levels in ChIP experiments in relation to the
      histone levels may provide a useful complement to standard approaches. In the
      present study analysis of data in this way provides an alternative explanation
      for previously indicated repressive role of Gcn5 in gene transcription.

PMID- 23865463
TI  - Examining clinical supervision as a mechanism for changes in practice: a research
      protocol.
AB  - AIM: This paper describes the research protocol for a study exploring if and how
      clinical supervision facilitates change in practice relating to psychosocial
      aspects of care for Health Professionals, who have been trained to deliver a
      psychosocial intervention to adults with cancer. BACKGROUND: There is a
      recognized need to implement care that is in line with clinical practice
      guidelines for the psychosocial care of adults with cancer. Clinical supervision
      is recommended as a means to support Health Professionals in providing the
      recommended psychosocial care. DESIGN: A qualitative design embedded within an
      experimental, stepped wedge randomized control trial. METHODS: The study will use
      discourse analysis to analyse audio-recorded data collected in clinical
      supervision sessions that are being delivered as one element of a large
      randomized control trial. The sessions will be attended primarily by nurses, but
      including physiotherapists, radiation therapists, occupational therapists. The
      Health Professionals are participants in a randomized control trial designed to
      reduce anxiety and depression of distressed adults with cancer. The sessions will
      be facilitated by psychiatrists experienced in psycho-oncology and the provision
      of clinical supervision. DISCUSSION: The proposed research is designed
      specifically to facilitate exploration of the mechanisms by which clinical
      supervision enables Health Professionals to deliver a brief, tailored
      psychosocial intervention in the context of their everyday practice. This is the
      first study to use discourse analysis embedded within an experimental randomized
      control trial to explore the mechanisms of change generated within clinical
      supervision by analysing the discourse within the clinical supervision sessions.

PMID- 23865465
TI  - Crystalline forms of 2,2,2-trifluoro-N-[(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol
      5-yl]oxy}-1-(3-methoxyphenyl)-2-propanyl]acetamide (AZD-5423).
AB  - A crystalline form (form B) of the novel glucocorticoid receptor agonist 2,2,2
      trifluoro-N-[(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(3
      methoxyphenyl)-2-propanyl]acetamide (AZD-5423) and its use alone or in
      combination for the treatment of asthma and chronic obstructive pulmonary disease
      are claimed. This form of AZD-5423 is better absorbed than Form A drug after
      inhalation. Two effective large-scale syntheses of AZD-5423 are described.

PMID- 23865466
TI  - [5]Radialene-fused tetrathiafulvalenes exhibiting a simultaneous four- or eight
      electron transfer.
AB  - Novel bis- and tris-fused tetrathiafulvalene (TTF) analogs possessing
      [5]radialene with quintuple 1,3-dithiol-2-ylidene moieties (2-4) were
      successfully synthesized. Cyclic voltammetry and differential pulse voltammetry
      revealed that they exhibited a simultaneous four- or eight-electron transfer
      process. It is suggested that four positive charges are distributed mainly over
      each of one or two DT[5]radialene units in 2(4+), 3(4+), and 4(8+). 

PMID- 23865464
TI  - Age-dependent parathormone levels and different CKD-MBD treatment practices of
      dialysis patients in Hungary--results from a nationwide clinical audit.
AB  - BACKGROUND: Achieving target levels of laboratory parameters of bone and mineral
      metabolism in chronic kidney disease (CKD) patients is important but also
      difficult in those living with end-stage kidney disease. This study aimed to
      determine if there are age-related differences in chronic kidney disease-mineral
      and bone disorder (CKD-MBD) characteristics, including treatment practice in
      Hungarian dialysis patients. METHODS: Data were collected retrospectively from a
      large cohort of dialysis patients in Hungary. Patients on hemodialysis and
      peritoneal dialysis were also included. The enrolled patients were allocated into
      two groups based on their age (<65 years and >=65 years). Characteristics of the
      age groups and differences in disease-related (epidemiology, laboratory, and
      treatment practice) parameters between the groups were analyzed. RESULTS: A total
      of 5008 patients were included in the analysis and the mean age was 63.4+/-14.2
      years. A total of 47.2% of patients were women, 32.8% had diabetes, and 11.4%
      were on peritoneal dialysis. Diabetes (37.9% vs 27.3%), bone disease (42.9% vs
      34.1%), and soft tissue calcification (56.3% vs 44.7%) were more prevalent in the
      older group than the younger group (p<0.001 for all). We found an inverse
      relationship between age and parathyroid hormone (PTH) levels (p<0.001). Serum
      PTH levels were lower in patients with diabetes compared with those without
      diabetes below 80 years (p<0.001). Diabetes and age were independently associated
      with serum PTH levels (interaction: diabetes * age groups, p=0.138). Older
      patients were more likely than younger patients to achieve laboratory target
      ranges for each parameter (Ca: 66.9% vs 62.1%, p<0.001; PO4: 52.6% vs 49.2%,
      p<0.05; and PTH: 50.6% vs 46.6%, p<0.01), and for combined parameters (19.8% vs
      15.8%, p<0.001). Older patients were less likely to receive related medication
      than younger patients (66.9% vs 79.7%, p<0.001). CONCLUSIONS: The achievement of
      laboratory target ranges for bone and mineral metabolism and clinical practice in
      CKD depends on the age of the patients. A greater proportion of older patients
      met target criteria and received less medication compared with younger patients.

PMID- 23865467
TI  - Observational study of hypertension and snoring in Northeastern Italy (Limana
      Hypertension Study).
AB  - OBJECTIVE: To evaluate through an observational study on volunteers some
      important cardiovascular disease risk factors such as hypertension and snoring in
      a population from Limana, a town of a subalpine zone of northeastern Italy.
      DESIGN: Limana residents were informed by post and at a public meeting and then
      attended an outpatient clinic set up by the town of Limana for clinical history,
      measurement of blood pressure, weight and height. PATIENTS: Of 202 subjects (94
      men and 108 women), 92.6% of whom were residents of Limana, having a mean age of
      59.7 years, which was significantly higher than the mean (44.7 years), took part
      in the study. RESULTS: Only 32.3% of study subjects with hypertension had normal
      blood pressure values while 38.6% of the subjects without hypertension treatment,
      were hypertensive. We found no significant association between hypertension and
      smoking and there were significant associations between hypertension and age and
      hypertension and snoring. CONCLUSIONS: Given the limitations of an observational
      study based on volunteer participation, nevertheless, our study presents some
      interesting results: (1) a low number of subjects with hypertension whose blood
      pressure is well controlled; (2) a significant number of "normal" subjects with
      high values of blood pressure; (3) no significant relationship between
      hypertension and smoking; (4) a significant relationship between subjects who
      snored and were hypertensive.

PMID- 23865468
TI  - Helicobacter pylori infection associates with a mucosal downregulation of
      ghrelin, negative regulator of Th1-cell responses.
AB  - BACKGROUND: Helicobacter pylori (Hp)-related gastritis is characterized by a
      predominant T helper (Th)1/Th17 cell immunity. Ghrelin (GR) has immunoregulatory
      properties and inhibits experimental Th cell-dependent pathology. AIMS: To
      evaluate whether Hp infection associates with changes in GR expression and
      whether GR negatively regulates Th1/Th17 cytokines during Hp infection. METHODS:
      GR expression was evaluated by real-time PCR in gastric biopsies taken from Hp
      infected and Hp-uninfected patients and in gastric biopsies of Hp-negative
      subjects cultured with or without H. pylori culture supernatant. To examine
      whether GR regulates Hp-induced cytokine production, H. pylori-infected gastric
      biopsies were stimulated with GR, and interleukin (IL)-12, interferon (IFN)-gamma
      and IL-4 transcripts were evaluated by real-time PCR. IL-12 and IFN-gamma were
      also analyzed in lamina propria mononuclear cells (LPMCs) extracted from Hp
      infected gastric biopsies and cultured with GR. RESULTS: GR RNA transcripts were
      reduced in biopsies from Hp-infected patients. Treatment of Hp-negative gastric
      biopsies with Hp culture supernatant reduced GR RNA expression. GR dose
      dependently inhibited RNA expression of IL-12 and IFN-gamma but not IL-4 in ex
      vivo cultures of mucosal explants and in cultures of gastric LPMCs from Hp
      positive patients. CONCLUSIONS: GR is downregulated in the gastric mucosa of H.
      pylori-infected patients. Such a defect could contribute to sustain the ongoing
      Th1-cell response.

PMID- 23865469
TI  - Hepatitis E virus in wild boar in the central northern part of Italy.
AB  - Hepatitis E virus (HEV) is responsible for sporadic acute hepatitis in developed
      countries, where the infection is acquired probably through ingestion of
      contaminated food, in addition to travel-related cases. In this study, the
      circulation of HEV in wild boar from nine Italian provinces was evaluated. An
      overall seroprevalence of 10.2% was found, although there were differences among
      the provinces, while no samples were positive for HEV RNA detection. This study
      indicates an active circulation of HEV in the Italian wild boar populations and
      suggests to consider the zoonotic risk in handling and eating meat from this
      animal. 

PMID- 23865470
TI  - Bioengineered cartilage in a scaffold-free method by human cartilage-derived
      progenitor cells: a comparison with human adipose-derived mesenchymal stromal
      cells.
AB  - The objective of our study was to investigate chondrogenesis potential of human
      adipose-derived mesenchymal stromal cells (MSCs), using as a positive control a
      human source of cartilage-derived progenitor cells (PCs). This source of PCs was
      recently described by our group and dwells on the surface of nasoseptal
      cartilage. Histological analysis using Safranin O staining and immunofluorescence
      for actin filaments and collagen type II was performed on three-dimensional (3D)
      pellet cultures. Cartilage PCs and adipose MSCs showed similarities in monolayer
      culture related to cell morphology and proliferation. Our 3D pellet cultures
      substantially reduced the actin stress and after 21 days under chondrogenic
      medium, we observed an increase in the pellet diameter for cartilage PCs (7.4%)
      and adipose MSCs (21.2%). Adipose-derived MSCs responded to chondrogenic
      stimulus, as seen by positive areas for collagen type II, but they were not able
      to recreate a mature extracellular matrix. Using semi-quantitative analysis, we
      observed a majority of Safranin O areas rising from blue (no stain) to orange
      (moderate staining) and no changes in fibroblastic morphology (P < 0.0001). For
      cartilage PCs, chondrogenic induction is responsible for morphological changes
      and a high percentage of matrix area/number of cells (P <= 0.0001), evaluated by
      computerized histomorphometry. Morphological analyses reveal that adipose-derived
      MSCs were not able to recreate a bioengineered cartilage. The cost of culture was
      reduced, as the cartilage PCs under growth-factor free medium exhibit a high
      score for cartilage formation compared with the induced adipose mesenchymal
      stromal cells (P = 0.0021). Using a pellet 3D culture, our cartilage PCs were
      able to produce a cartilage tissue in vitro, leading to the future development of
      bioengineered products.

PMID- 23865471
TI  - Mono- and dinuclear cationic iridium(III) complexes bearing a 2,5
      dipyridylpyrazine (2,5-dpp) ligand.
AB  - The synthesis, X-ray structures, photophysical, and electrochemical
      characterization of mono- (1) and dinuclear (2) cationic iridium(III) complexes
      bearing a 2,5-dipyridylpyrazine (2,5-dpp) ancillary ligand are reported. Upon the
      complexation of a first equivalent of iridium, the photoluminescence shifts
      markedly into the deep red (lambdaem = 710 nm, PhiPL = 0.9%) compared to other
      cationic iridium complexes such as [Ir(ppy)2(bpy)]PF6. With the coordination of a
      second equivalent of iridium, room temperature luminescence is completely
      quenched. Both 1 and 2 are luminescent at low temperatures but with distinct
      excited state decay kinetics; the emission of 2 is significantly red-shifted
      compared to 1. Emission both at 298 and 77 K results from a mixed charge-transfer
      state. Density functional theory (DFT) calculations and electrochemical behavior
      point to an electronic communication between the two iridium complexes. 

PMID- 23865472
TI  - Fluorescence resonance energy transfer in microemulsions composed of tripled
      chain surface active ionic liquids, RTILs, and biological solvent: an excitation
      wavelength dependence study.
AB  - In this article we have reported the fluorescence resonance energy transfer
      (FRET) study in our earlier characterized surface active ionic liquids (SAILs)
      containing microemulsion, i.e., N-methyl-N-propylpyrrolidinium
      bis(trifluoromethanesulfonyl)imide ([P13][Tf2N])/[CTA][AOT]/isopropyl myristate
      ([IPM]) and N,N,N-trimethyl-N-propylammonium bis(trifluoromethanesulfonyl)imide
      ([N3111][Tf2N])/[CTA][AOT]/[IPM] microemulsions (Banerjee, C.; Mandal, S.; Ghosh,
      S.; Kuchlyan, J.; Kundu, N.; Sarkar, N. J. Phys. Chem. B 2013, 117, 3927-3934).
      The occurrence of effective FRET from the donor, coumarin-153 (C-153) to the
      acceptor rhodamine 6G (R6G) is evident from the decrease in the steady state
      fluorescence intensity of the donor with addition of acceptor and subsequent
      increase in the fluorescence intensity of the acceptor in the presence of donor.
      The excitation wavelength dependent FRET from C-153 to R6G has also been
      performed to assess the dynamic heterogeneity of these confined systems. In time
      resolved experiments, the significant rise time of the acceptor in the presence
      of the donor further confirms the occurrence of FRET. The multiple donor-acceptor
      (D-A) distances, for various microemulsions, obtained from the rise times of the
      acceptor emission in the presence of a donor can be rationalized from the varying
      distribution of the donor, C-153, in the different regions of the microemulsion.
      Time-resolved measurement reveals that with increasing excitation wavelength from
      408 to 440 nm, the contribution of the faster rise component of FRET increases
      significantly due to the close proximity of the C-153 and R6G in the polar region
      of the microemulsion where occurrence of FRET is very high. Moreover, we have
      also studied the FRET with variation of R (R = [room temperature ionic liquids
      (RTILs)]/[surfactant]) and shown that the effect of excitation wavelength on FRET
      is similar irrespective of R values. 

PMID- 23865473
TI  - Anti-miRNA-23a oligonucleotide suppresses glioma cells growth by targeting
      apoptotic protease activating factor-1.
AB  - BACKGROUND: Abnormal expression of microRNAs (miRNAs) is closely related to
      glioma, which is one of the most common malignant brain tumors. The current study
      is to identify the key miRNAs involved in the pathogenesis of glioma and to
      discover novel therapeutic targets for this disease. MATERIALS AND METHODS: Total
      RNA was extracted from glioma tissues of 100 patients. The microRNA microarray
      and the northern blot were used to detect the changes of miRNAs expression in 7
      pairs of glioma specimens. Relative expressions of miR-23a were validated by real
      time reverse transcription polymerase chain reaction (RT-PCR) with specific
      Taqman probes. In order to evaluate the role of miR-23a, the miR-23a mimics and
      anti-miR-23a oligonucleotides were transfected to glioma cell lines; the cell
      proliferation, apoptosis, cell cycle percentage, cell migration and invasion
      abilities were evaluated in vitro. The target genes of miR-23a were also
      investigated using the bioinformatics tools. The expression of the apoptotic
      protease activating factor-1 (APAF1), which might be one of the direct targets of
      miR-23a, was also analyzed using the luciferase reporter assay and western blot
      analysis in 293T cells and glioma cell line, respectively. RESULTS: The microRNA
      microarray and the northern blot results showed that the expressions of miR-23a
      in glioma tissues were significantly upregulated. The miR-23a expression levels
      identified using real time RT-PCR in tumor tissues of 79 samples were higher than
      in the matched adjacent tissues. By transfection of anti-miR-23a oligonucleotide,
      the results showed that the proliferation, migration, and invasion of glioma cell
      lines were significantly suppressed. The bioinformatics searching results showed
      that APAF1 might be a direct target gene of miR-23a, and it was supported by the
      luciferase reporter gene assay and western blot analysis results. Finally,
      experiments showed that overexpression of APAF1 suppressed glioma cell growth and
      promoted cell apoptosis. CONCLUSIONS: Our findings characterized the expression
      properties of miR-23a, contributed to the function and molecular mechanism of miR
      23a in glioma and implied that miR-23a might be employed as novel prognostic
      markers and therapeutic targets of glioma.

PMID- 23865474
TI  - Applicability of cranial models in urethane resin and foam as a substitute for
      bone: are synthetic materials reliable?
AB  - As literature is poor in functional synthetic cranial models, in this study,
      synthetic handmade models of cranial vaults were produced in two different
      materials (a urethane resin and a self-hardening foam), from multiple bone
      specimens (eight original cranial vaults: four human and four swine), in order to
      test their resemblance to bone structure in behavior, during fracture formation.
      All the vaults were mechanically tested with a 2-kg impact weight and filmed with
      a high-speed camera. Fracture patterns were homogeneous in all swine vaults and
      heterogeneous in human vaults, with resin fractures more similar to bone
      fractures. Mean fracture latency time extrapolated by videos were of 0.75 msec
      (bone), 1.5 msec (resin), 5.12 msec (foam) for human vaults and of 0.625 msec
      (bone), 1.87 msec (resin), 3.75 msec (foam) for swine vaults. These data showed
      that resin models are more similar to bone than foam reproductions, but that
      synthetic material may behave quite differently from bone as concerns fracture
      latency times. 

PMID- 23865475
TI  - Hydrogel-based microactuators with remote-controlled locomotion and fast Pb2+
      response for micromanipulation.
AB  - Hydrogel-based microactuators that enable remote-controlled locomotion and fast
      Pb(2+)-response for micromanipulation in Pb(2+)-polluted microenvironment have
      been fabricated from quadruple-component double emulsions. The microactuators are
      Pb(2+)-responsive poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide)
      microgels, each with an eccentric magnetic core for magnetic manipulation and a
      hollow cavity for fast Pb(2+)-response. Micromanipulation of the microactuators
      is demonstrated by using them for preventing Pb(2+)-leakage from microchannel.
      The microactuators can be remotely and precisely transported to the Pb(2+)
      leaking site under magnetic guide, and then clog the microchannel with Pb(2+)
      responsive volume swelling to prevent flowing out of Pb(2+)-contaminated
      solution. The proposed microactuator structure provides a potential and novel
      model for developing multifunctional actuators and sensors, biomimetic soft
      microrobots, microelectro-mechanical systems and drug delivery systems. 

PMID- 23865476
TI  - A natural robustification of the ordinary instrumental variables estimator.
AB  - Instrumental variables estimators are designed to provide consistent parameter
      estimates for linear regression models when some covariates are correlated with
      the error term. We propose a new robust instrumental variables estimator (RIV)
      which is a natural robustification of the ordinary instrumental variables
      estimator (OIV). Specifically, we construct RIV using a robust multivariate
      location and scatter S-estimator to robustify the solution of the estimating
      equations that define OIV. RIV is computationally inexpensive and readily
      available for applications through the R-library riv. It has attractive
      robustness and asymptotic properties, including high resilience to outliers,
      bounded influence function, consistency under weak distributional assumptions,
      asymptotic normality under mild regularity conditions, and equivariance. We
      further endow RIV with an iterative algorithm which allows for the estimation of
      models with endogenous continuous covariates and exogenous dummy covariates. We
      study the performance of RIV when the data contains outliers using an extensive
      Monte Carlo simulation study and by applying it to a limited-access dataset from
      the Framingham Heart Study-Cohort to estimate the effect of long-term systolic
      blood pressure on left atrial size. 

PMID- 23865477
TI  - Ecological divergence and speciation between lemur (Eulemur) sister species in
      Madagascar.
AB  - Understanding ecological niche evolution over evolutionary timescales is crucial
      to elucidating the biogeographic history of organisms. Here, we used, for the
      first time, climate-based ecological niche models (ENMs) to test hypotheses about
      ecological divergence and speciation processes between sister species pairs of
      lemurs (genus Eulemur) in Madagascar. We produced ENMs for eight species, all of
      which had significant validation support. Among the four sister species pairs, we
      found nonequivalent niches between sisters, varying degrees of niche overlap in
      ecological and geographic space, and support for multiple divergence processes.
      Specifically, three sister-pair comparisons supported the null model that niches
      are no more divergent than the available background region. These findings are
      consistent with an allopatric speciation model, and for two sister pairs (E.
      collaris-E. cinereiceps and E. rufus-E. rufifrons), a riverine barrier has been
      previously proposed for driving allopatric speciation. However, for the fourth
      sister pair E. flavifrons-E. macaco, we found support for significant niche
      divergence, and consistent with their parapatric distribution on an ecotone and
      the lack of obvious geographic barriers, these findings most strongly support a
      parapatric model of speciation. These analyses thus suggest that various
      speciation processes have led to diversification among closely related Eulemur
      species. 

PMID- 23865478
TI  - Lentils (Lens culinaris L.), a rich source of folates.
AB  - The potential for genetic biofortification of U.S.-grown lentils ( Lens culinaris
      L.) with bioavailable folate has not been widely studied. The objectives of this
      study were (1) to determine the folate concentration of 10 commercial lentil
      cultivars grown in Minot and McLean counties, North Dakota, USA, in 2010 and
      2011, (2) to determine the genotype (G) * environmental (E) interactions for
      folate concentration in lentil cultivars, and (3) to compare the folate
      concentration of other pulses [field peas ( Pisum sativum L.) and chickpea (
      Cicer arietinum L.)] grown in the United States. Folate concentration in lentil
      cultivars ranged from 216 to 290 MUg/100 g with a mean of 255 MUg/100 g. In
      addition, lentil showed higher folate concentration compared to chickpea (42-125
      MUg/100 g), yellow field pea (41-55 MUg/100 g), and green field pea (50-202
      MUg/100 g). A 100 g serving of lentils could provide a significant amount of the
      recommended daily allowance of dietary folates (54-73%) for adults. A significant
      year * location interaction on lentil folate concentration was observed; this
      indicates that possible location sourcing may be required for future lentil
      folate research.

PMID- 23865479
TI  - Intermediate instability at high temperature leads to low pathway efficiency for
      an in vitro reconstituted system of gluconeogenesis in Sulfolobus solfataricus.
AB  - Four enzymes of the gluconeogenic pathway in Sulfolobus solfataricus were
      purified and kinetically characterized. The enzymes were reconstituted in vitro
      to quantify the contribution of temperature instability of the pathway
      intermediates to carbon loss from the system. The reconstituted system,
      consisting of phosphoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase,
      triose phosphate isomerase and the fructose 1,6-bisphosphate
      aldolase/phosphatase, maintained a constant consumption rate of 3
      phosphoglycerate and production of fructose 6-phosphate over a 1-h period.
      Cofactors ATP and NADPH were regenerated via pyruvate kinase and glucose
      dehydrogenase. A mathematical model was constructed on the basis of the kinetics
      of the purified enzymes and the measured half-life times of the pathway
      intermediates. The model quantitatively predicted the system fluxes and
      metabolite concentrations. Relative enzyme concentrations were chosen such that
      half the carbon in the system was lost due to degradation of the thermolabile
      intermediates dihydroxyacetone phosphate, glyceraldehyde 3-phosphate and 1,3
      bisphosphoglycerate, indicating that intermediate instability at high temperature
      can significantly affect pathway efficiency.

PMID- 23865480
TI  - Is valganciclovir really effective in primary effusion lymphoma: case report of
      an HIV(-) EBV(-) HHV8(+) patient.
AB  - Primary effusion lymphoma (PEL) is a human herpesvirus 8 (HHV8) associated
      lymphoproliferative disease characterized by effusions in body cavities, and lack
      of tumor mass. Valganciclovir is a treatment option in PEL, however, little is
      known about its clinical efficacy. Ganciclovir has been reported to be effective
      in HHV8(+) multicentric Castleman's disease (MCD) by decreasing the plasma HHV8
      load, which is an important factor in the induction and persistence of MCD,
      Kaposi's sarcoma (KS), and PEL. But there is no information about the efficacy of
      valganciclovir on HHV8 associated lymphoproliferative diseases. Here, we present
      the first EBV and HIV negative, HHV8 positive PEL case treated with
      valganciclovir; for whom it initially reduced the viral load leading to a
      transient partial improvement in the clinical status, but failed to induce a
      complete and durable remission. 

PMID- 23865481
TI  - Oxaliplatin induces different cellular and molecular chemoresistance patterns in
      colorectal cancer cell lines of identical origins.
AB  - BACKGROUND: Cancer cells frequently adopt cellular and molecular alterations and
      acquire resistance to cytostatic drugs. Chemotherapy with oxaliplatin is among
      the leading treatments for colorectal cancer with a response rate of 50%,
      inducing intrastrand cross-links on the DNA. Despite of this drug's efficiency,
      resistance develops in nearly all metastatic patients. Chemoresistance being of
      crucial importance for the drug's clinical efficiency this study aimed to
      contribute to the identification and description of some cellular and molecular
      alterations induced by prolonged oxaliplatin therapy. Resistance to oxaliplatin
      was induced in Colo320 (Colo320R) and HT-29 (HT-29R) colorectal adenocarcinoma
      cell lines by exposing the cells to increasing concentrations of the drug.
      Alterations in morphology, cytotoxicity, DNA cross-links formation and gene
      expression profiles were assessed in the parental and resistant variants with
      microscopy, MTT, alkaline comet and pangenomic microarray assays, respectively.
      RESULTS: Morphology analysis revealed epithelial-to-mesenchymal transition in the
      resistant vs parental cells suggesting alterations of the cells' adhesion
      complexes, through which they acquire increased invasiveness and adherence.
      Cytotoxicity measurements demonstrated resistance to oxaliplatin in both cell
      lines; Colo320 being more sensitive than HT-29 to this drug (P < 0.001). The
      treatment with oxaliplatin caused major DNA cross-links in both parental cell
      lines; in Colo320R small amounts of DNA cross-links were still detectable, while
      in HT-29R not. We identified 441 differentially expressed genes in Colo320R and
      613 in HT-29R as compared to their parental counterparts (at least 1.5 -fold up-
      or down- regulation, p < 0.05). More disrupted functions and pathways were
      detected in HT-29R cell line than in Colo320R, involving genes responsible for
      apoptosis inhibition, cellular proliferation and epithelial-to-mesenchymal
      transition. Several upstream regulators were detected as activated in HT-29R cell
      line, but not in Colo320R. CONCLUSIONS: Our findings revealed a more resistant
      phenotype in HT-29R as compared to Colo320R and different cellular and molecular
      chemoresistance patterns induced by prolonged treatment with oxaliplatin in cell
      lines with identical origins (colorectal adenocarcinomas).

PMID- 23865482
TI  - A pearl protein self-assembles to form protein complexes that amplify
      mineralization.
AB  - The formation of the nacre pearl in marine invertebrates represents an on-demand
      production of mineralization in response to an irritant or parasite threat to the
      mantle organ. In the Japanese pearl oyster (Pinctada fucata), this process is
      mediated by a 12-member protein family known as PFMG (Pinctada fucata mantle
      gene). One of these proteins, PFGM1, has been implicated in modulating calcium
      carbonate crystal growth and has been reported to possess an EF-hand-like domain.
      In this report, we establish that the recombinant PFMG1 (rPFMG1) is an
      intrinsically disordered "imitator" EF-hand protein that increases the number of
      calcium carbonate mineral crystals that form relative to control scenarios and
      does not induce aragonite formation. This protein possesses a modified pseudo-EF
      hand sequence at the C-terminal end which exhibits low homology (30-40%) to the
      pseudo-EF-hand mitochondrial SCaMCs buffering/solute transport proteins. This low
      sequence homology is the result of the inclusion of disorder-promoting amino
      acids and short amyloid-like aggregation-prone cross-beta-strand sequences within
      the putative PFMG1 pseudo-EF-hand sequence region. Similar to other nacre
      proteins, rPFMG1 oligomerizes to form amorphous, heterogeneously sized protein
      oligomers and films in vitro, and this process is enhanced by Ca(2+), which
      promotes the formation of aggregation-prone extended beta-strand structure within
      rPFMG1. From these results, we conclude that PFMG1 forms supramolecular
      assemblies that play an important role in amplifying the nucleation process that
      is crucial for coating or neutralizing invasive threats to the mantle organ. 

PMID- 23865484
TI  - A mixed-method systematic review: support for ethical competence of nurses.
AB  - AIM: The aim was to appraise and synthesize evidence of empirical studies of how
      nurses' ethical competence can be supported. BACKGROUND: Ethical competence is an
      essential element of nursing practice. Nurses increasingly need support in
      competence when carrying out their responsibilities towards their patients.
      DESIGN: A mixed-method systematic review of quantitative and qualitative studies
      was undertaken according to the University of York's Centre for Reviews and
      Dissemination guidelines. DATA SOURCES: Searches of MEDLINE, Nursing Database and
      British Nursing Index databases were conducted, yielding 512 citations between
      1985-2012. METHODS: After a two-stage application of inclusion and exclusion
      criteria, 34 articles were included. The quality of the studies was assessed
      using STROBE or COREQ criteria. Data were analysed by content analysis. RESULTS:
      Nurses' ethical competence has been studied from different viewpoints: ethical
      decision-making, ethical sensitivity, ethical knowledge and ethical reflection.
      There was little empirical evidence of provided support, but studies offered
      recommendations on how to support ethical competence. The most common strategies
      to support ethical competence were ethics education, ethics rounds, ethics
      committee and consultation. Nurse leaders and colleagues have a key role in
      providing opportunities for nurses to gain ethical competence. CONCLUSIONS: There
      is a need to develop evidence-based support at the organizational and individual
      level to support nurses' ethical competence. Barriers for multiprofessional
      cooperation in ethical issues should be recognized and addressed as part of the
      development of organizational ethical practices. Research should pay more
      attention to the conceptual, theoretical and practical perspectives of ethical
      competence.

PMID- 23865483
TI  - The Norwegian Stroke in the Young Study (NOR-SYS): rationale and design.
AB  - BACKGROUND: Ischemic stroke in young adults is a major health problem being
      associated with a higher vascular morbidity and mortality compared to controls,
      and a stroke recurrence rate of 25% during the first decade. The assumed cause of
      infarction and the detected risk factors determine the early- and long-term
      treatment. However, for many patients the cause of stroke remains unknown. Risk
      factor profile and etiology differ in young and elderly ischemic stroke patients,
      and atherosclerosis is the determined underlying condition in 10 to 15%. However,
      subclinical atherosclerosis is probably more prevalent and may go unrecognized.
      METHODS/DESIGN: NOR-SYS is a prospective long-term research program. Standardized
      methods are used for anamnestic, clinical, laboratory, imaging, and ultrasound
      data collection in ischemic stroke patients aged <=60 years, their partners and
      joint adult offspring. The ultrasound protocol includes the assessment of
      intracranial, carotid and femoral arteries, abdominal aorta, and the estimation
      of VAT. To date, the study is a single centre study with approximately 400
      patients, 250 partners and 350 adult offspring expected to be recruited at our
      site. DISCUSSION: NOR-SYS aims to increase our knowledge about heredity and the
      development of arterial vascular disease in young patients with ischemic stroke
      and their families. Moreover, optimization of diagnostics, prophylaxis and early
      intervention are major targets with the intention to reduce stroke recurrence and
      other clinical arterial events, physical disability, cognitive impairment and
      death.

PMID- 23865485
TI  - The gastrin receptor antagonist netazepide (YF476) prevents oxyntic mucosal
      inflammation induced by Helicobacter pylori infection in Mongolian gerbils.
AB  - OBJECTIVE: Long-term Helicobacter pylori infection causes gastritis leading to
      hypergastrinemia and predisposes to gastric cancer. Our aim was to assess the
      role of gastrin in oxyntic mucosal inflammation in H. pylori-infected Mongolian
      gerbils by means of the gastrin receptor antagonist netazepide (YF476). DESIGN:
      We studied 60 gerbils for 18 months and left five animals uninfected (control
      group), inoculated 55 with H. pylori, and treated 28 of the infected animals with
      netazepide (Hp+YF476 group). Twenty-seven infected animals were given no
      treatment (Hp group). We measured plasma gastrin and intraluminal pH. H. pylori
      detection and histologic evaluations of the stomach were carried out. RESULTS:
      All 55 inoculated animals were H. pylori positive at termination. Eighteen
      animals in the Hp group had gastritis. There was a threefold increase in mucosal
      thickness in the Hp group compared to the Hp+YF476 group, and a threefold
      increase in oxyntic neuroendocrine cells in the Hp group compared to the Hp+YF476
      group (p < .05). All animals in the Hp+YF476 group had macro- and microscopically
      normal findings in the stomach. Plasma gastrin was higher in the Hp group than in
      the control group (172 +/- 16 pmol/L vs 124 +/- 5 pmol/L, p < .05) and highest in
      the Hp+YF476 group (530 +/- 36 pmol/L). Intraluminal pH was higher in the Hp
      group than in the Hp+YF476 group (2.51 vs 2.30, p < .05). CONCLUSION: The gastrin
      antagonist netazepide prevents H. pylori-induced gastritis in Mongolian gerbils.
      Thus, gastrin has a key role in the inflammatory reaction of the gastric mucosa
      to H. pylori infection in this species.

PMID- 23865486
TI  - Genes of the RNASE5 pathway contain SNP associated with milk production traits in
      dairy cattle.
AB  - BACKGROUND: Identification of the processes and mutations responsible for the
      large genetic variation in milk production among dairy cattle has proved
      challenging. One approach is to identify a biological process potentially
      involved in milk production and to determine the genetic influence of all the
      genes included in the process or pathway. Angiogenin encoded by angiogenin,
      ribonuclease, RNase A family 5 (RNASE5) is relatively abundant in milk, and has
      been shown to regulate protein synthesis and act as a growth factor in epithelial
      cells in vitro. However, little is known about the role of angiogenin in the
      mammary gland or if the polymorphisms present in the bovine RNASE5 gene are
      associated with lactation and milk production traits in dairy cattle. Given the
      high economic value of increased protein in milk, we have tested the hypothesis
      that RNASE5 or genes in the RNASE5 pathway are associated with milk production
      traits. First, we constructed a "RNASE5 pathway" based on upstream and downstream
      interacting genes reported in the literature. We then tested SNP in close
      proximity to the genes of this pathway for association with milk production
      traits in a large dairy cattle dataset. RESULTS: The constructed RNASE5 pathway
      consisted of 11 genes. Association analysis between SNP in 1 Mb regions
      surrounding these genes and milk production traits revealed that more SNP than
      expected by chance were associated with milk protein percent (P < 0.05
      significance). There was no significant association with other traits such as
      milk fat content or fertility. CONCLUSIONS: These results support a role for the
      RNASE5 pathway in milk production, specifically milk protein percent, and
      indicate that polymorphisms in or near these genes explain a proportion of the
      variation for this trait. This method provides a novel way of understanding the
      underlying biology of lactation with implications for milk production and can be
      applied to any pathway or gene set to test whether they are responsible for the
      variation of complex traits.

PMID- 23865487
TI  - Understanding recruitment: outcomes associated with alternate methods for seed
      selection in respondent driven sampling.
AB  - BACKGROUND: Respondent driven sampling (RDS) was designed for sampling "hidden"
      populations and intended as a means of generating unbiased population estimates.
      Its widespread use has been accompanied by increasing scrutiny as researchers
      attempt to understand the extent to which the population estimates produced by
      RDS are, in fact, generalizable to the actual population of interest. In this
      study we compare two different methods of seed selection to determine whether
      this may influence recruitment and RDS measures. METHODS: Two seed groups were
      established. One group was selected as per a standard RDS approach of study staff
      purposefully selecting a small number of individuals to initiate recruitment
      chains. The second group consisted of individuals self-presenting to study staff
      during the time of data collection. Recruitment was allowed to unfold from each
      group and RDS estimates were compared between the groups. A comparison of
      variables associated with HIV was also completed. RESULTS: Three analytic groups
      were used for the majority of the analyses-RDS recruits originating from study
      staff-selected seeds (n = 196); self-presenting seeds (n = 118); and recruits of
      self-presenting seeds (n = 264). Multinomial logistic regression demonstrated
      significant differences between the three groups across six of ten
      sociodemographic and risk behaviours examined. Examination of homophily values
      also revealed differences in recruitment from the two seed groups (e.g. in one
      arm of the study sex workers and solvent users tended not to recruit others like
      themselves, while the opposite was true in the second arm of the study). RDS
      estimates of population proportions were also different between the two
      recruitment arms; in some cases corresponding confidence intervals between the
      two recruitment arms did not overlap. Further differences were revealed when
      comparisons of HIV prevalence were carried out. CONCLUSIONS: RDS is a cost
      effective tool for data collection, however, seed selection has the potential to
      influence which subgroups within a population are accessed. Our findings indicate
      that using multiple methods for seed selection may improve access to hidden
      populations. Our results further highlight the need for a greater understanding
      of RDS to ensure appropriate, accurate and representative estimates of a
      population can be obtained from an RDS sample.

PMID- 23865488
TI  - NT-proBNP predicts impaired myocardial function in newly diagnosed hypertensive
      patients with preserved ejection fraction.
AB  - N-terminal pro-brain natriuretic peptide (NT-proBNP) is an excellent biomarker to
      diagnose left ventricular (LV) dysfunction. LV myocardial performance index (MPI
      Tei index) is commonly used as a measure of combined systolic and diastolic
      function. We aimed to investigate the relationship between NT-proBNP and tissue
      Doppler derived MPI in newly diagnosed hypertensive patients with preserved LV
      ejection fraction (LVEF). We studied 236 patients with newly diagnosed HT (mean
      age; 52.9 +/- 5.2 years). Echocardiographic examination was performed in all
      patients. LV mass index (LVMI) was calculated. Conventional Doppler indices (E
      and A waves) were recorded. The MPI value was obtained from the tissue Doppler
      derived ejection time, isovolumic contraction and relaxation times. The patients
      were divided into two groups according to the median NT-proBNP value (NT
      proBNPlow group <114 pg/ml and NT-proBNPhigh group >=114 pg/ml). Patients with NT
      proBNPhigh were older and had higher levels of glucose and creatinine, lower E/A
      ratio and higher LVMI and MPI values than patients with NT-proBNPlow. However,
      LVEF were similar among the groups. Multiple linear regression analysis showed
      that NT-proBNP was independently associated with age, LVMI, MPI and E/A ratio.
      Increased NT-proBNP level was independently associated with impaired myocardial
      performance index in newly diagnosed hypertensive patients with preserved LVEF.

PMID- 23865489
TI  - Models of mortality probability in severe traumatic brain injury: results of the
      modelling by the UK trauma registry.
AB  - Currently available prognostic models in Traumatic Brain Injury (TBI) are derived
      from historical data sets or from heterogeneous data sets, depending upon the
      trauma care delivered. The objective of our study was to develop models to
      predict survival in a recent cohort of TBI patients within a relatively
      homogeneous trauma care system. Records of patients with brain injury were
      extracted from the Trauma Audit and Research Network (TARN) database. The
      relationship of the variables (i.e., age, Glasgow Coma Score [GCS], pupillary
      reactivity, Injury Severity Score [ISS], Computed Tomography [CT]
      classifications, classification of various intracranial pathologies, systolic and
      mean blood pressure, oxygen saturation, and the presence of extracranial injury)
      to survival at discharge were determined. Stepwise logistical regression analysis
      was performed to determine the best prognostic model. Two models were derived
      from data of 802 patients (models A and B). Age, GCS, pupillary reactivity,
      hypoxia, and brainstem injury are significant predictors in both. However, model
      A contains ISS in contrast to model B, which contains the presence of brain
      swelling and major extracranial injury instead. Both models have good predictive
      performance (model A: area under the Receiver Operating Characteristic [ROC]
      curve [AUC]=0.92 [95% CI, 0.90-0.95], Nagelkerke R(2), 0.62; model B: AUC=0.93
      [95% CI: 0.91-0.95], Nagelkerke R(2): 0.63). Hence, two accurate and reliable
      prognostic models were developed from a recent cohort of the TBI population.

PMID- 23865490
TI  - The influence of different metabolic syndrome definitions in predicting
      vasculogenic erectile dysfunction: is there a role for the index of central
      obesity?
AB  - AIMS: Analyze the capacity of ICO, the ratio of waist circumference (WC) and
      height, in predicting hemodynamic impairment in Erectile Dysfunction (ED)
      patients, independently and integrated in Metabolic Syndrome (MetS) definitions.
      METHODS: Four hundred and eighty-five ED patients followed in Urology consult
      from January 2008 until March 2012 were evaluated by a standardized protocol:
      health questionnaire, anthropometric measurements (AM), blood pressure and
      analysis, and Penile Duplex Doppler Ultrasound (PDDU) exam. Associations between
      AM and MetS definitions, including ATPIII, IDF and a new definition replacing WC
      by ICO in ATPIII MetS definition (ModATPIII), and PDDU were calculated. RESULTS:
      ICO was the measure of obesity more strongly correlated with diminished mean Peak
      Systolic Velocity (mPSV) (r = -0.189, p < 0.001). A positive association remained
      when replacing WC by ICO >= 0.60 (a nationally obtained ratio) in ATPIII MetS
      definition (ModATPIII). Patients with ModATPIII had lower mPSV when compared to
      non-MetS patients (30.8 versus 37.1, p < 0.001). Only the IDF definition had a
      significant association with AD (OR = 1853; 95%CI, 1.202-2.857). CONCLUSIONS: ICO
      revealed potential value to predict PDDU changes in a MetS context. However, IDF
      definition presented a stronger correlation with arteriogenic ED. Although
      longitudinal studies are necessary to confirm this hypothesis, our study
      highlights the importance of different MetS definitions for ED assessment.

PMID- 23865491
TI  - Rhodium-catalyzed asymmetric hydroarylation of 3-pyrrolines giving 3
      arylpyrrolidines: protonation as a key step.
AB  - A hydroxorhodium complex coordinated with (R)-segphos was found to catalyze the
      hydroarylation of 3-pyrrolines with arylboroxines under neutral conditions to
      give 3-arylpyrrolidines with high enantioselectivity in high yields. 

PMID- 23865492
TI  - Strength and size ratios between reciprocal muscle groups in the thigh and lower
      leg of male collegiate soccer players.
AB  - This study investigated the strength and size ratios between reciprocal muscle
      groups in the thigh and lower leg of soccer players. In 11 male collegiate soccer
      players and 21 male non-soccer players, the joint torques developed during
      isometric maximal voluntary contractions of the knee extensors (TQ(KE)) and
      flexors (TQ(KF)), plantar flexors (TQ(PF)) and dorsiflexors (TQ(DF)) were
      determined using a dynamometer. The muscle volumes of the same muscles (i.e.
      MV(KE), MV(KF), MV(PF) and MV(DF)) were determined by magnetic resonance imaging.
      There were no significant differences in any of the joint torques or muscle
      volumes between soccer and non-soccer players. TQ(KE)/TQ(KF) was significantly
      lower for soccer players than for non-soccer players. On the other hand, no
      significant difference in TQ(PF)/TQ(DF) was found between soccer and non-soccer
      players. MV(KE)/MV(KF) and MV(PF)/MV(DF) for soccer players were not
      significantly different from those for non-soccer players. Additionally, there
      were no significant correlations between MV(KE)/MV(KF) and TQ(KE)/TQ(KF) and
      between MV(PF)/MV(DF) and TQ(PF)/TQ(DF) of soccer players. Thus, the strength
      ratios appear not to be affected by the size ratios between the knee extensors
      and flexors and between the plantar flexors and dorsiflexors in soccer players.

PMID- 23865493
TI  - Deoxygenation of mono-oxo bis(dithiolene) Mo and W complexes by protonation.
AB  - Protonation-assisted deoxygenation of a mono-oxo molybdenum center has been
      observed in many oxotransferases when the enzyme removes an oxo group to
      regenerate a substrate binding site. Such a reaction is reported here with
      discrete synthetic mono-oxo bis(dithiolene) molybdenum and tungsten complexes,
      the chemistry of which had been rarely studied because of the instability of the
      resulting deoxygenated products. An addition of tosylic acid to an acetonitrile
      solution of [Mo(IV)O(S2C2Ph2)2](2-) (1) and [W(IV)O(S2C2Ph2)2](2-) (2) results in
      the loss of oxide with a concomitant formation of novel deoxygenated complexes,
      [M(MeCN)2(S2C2Ph2)2] (M = Mo (3), W (4)), that have been isolated and
      characterized. Whereas protonation of 1 exclusively produces 3, two different
      reaction products can be generated from 2; an oxidized product, [WO(S2C2Ph2)2](
      ), is produced with 1 equiv of acid while a deoxygenated product,
      [W(MeCN)2(S2C2Ph2)2] (4), is generated with an excess amount of proton.
      Alternatively, complexes 3 and 4 can be obtained from photolysis of
      [Mo(CO)2(S2C2Ph2)2] (5) and [W(CO)2(S2C2Ph2)2] (6) in acetonitrile. A di- and a
      monosubstituted adducts of 3, [Mo(CO)2(S2C2Ph2)2] (5) and
      [Mo(PPh3)(MeCN)(S2C2Ph2)2] (7) are also reported. 

PMID- 23865494
TI  - Increased carbon monoxide production by hemeoxygenase-1 caused by device-mediated
      hemolysis: thrombotic phantom menace?
AB  - Replacement of key components of the circulatory system with artificial devices
      has become the mainstay of therapy for conditions such as end-stage valvular
      disease or congestive heart failure. Unfortunately, device thrombosis and
      thromboembolic morbidity persist despite optimized anticoagulation. This work
      reviews the commonly known causes of device-associated thrombophilia, introduces
      recent literature concerning the effect of carbon monoxide on coagulation, and
      presents new patient data linking endogenously produced carbon monoxide with
      device-associated thrombosis. A new paradigm involving the interaction of red
      blood cell lysis-induced upregulation of hemoxygenase-1, increased endogenous
      carbon monoxide, hyperfibrinogenemia, and contact protein/microparticle-induced
      thrombin generation is presented.

PMID- 23865495
TI  - Self-association and picosecond dynamics in liquid dimethyl sulfoxide.
AB  - Dimethyl sulfoxide (DMSO) has been known for almost 150 years, but its properties
      as a solvent and reaction medium are far from being understood. In particular,
      association equilibriums in liquid DMSO have been characterized in just four
      papers, and the enthalpy of its self-association is unknown. The aims of this
      paper are to study self-association equilibriums in neat liquid DMSO at various
      temperatures by means of Raman spectroscopy, to find the enthalpy of self
      association, and to solve the problem of hydrogen bonding in this liquid. Time
      correlation functions of vibrational dephasing and reorientation of coexisting
      monomers and dimers studied by the C-S-C and C-H symmetric vibrations indicate
      that external perturbations and vibrational and reorientational dynamics of these
      particles occur on different time scales. No signatures of H-bonding in DMSO are
      found. The association constants vary from 0.20 L mol(-1) (23  degrees C) to
      0.081 L mol(-1) (100  degrees C). Their temperature dependence gives the enthalpy
      of association of DMSO as -11.7 +/- 0.9 kJ mol(-1). 

PMID- 23865496
TI  - Formation of complex interface and stability of oil-in-water (O/W) emulsion
      prepared by soy lipophilic protein nanoparticles.
AB  - A lipophilic protein nanoparticle (LPP) was fabricated by ultrasonication of the
      soy lipophilic protein (LP), which contains hydrophobic proteins and
      phospholipids. This LPP (Rh = 136 +/- 0.8 nm, zeta-potential = -20 mV, pH 7.0)
      had an improved dispersibility and acted as an emulsifier. The oil/water (O/W)
      emulsion stabilized by this LPP exhibited superior physical stability over long
      term storage (8 weeks), during a stress storage test (200 mM NaCl addition and
      heating at 90  degrees C), and in the presence of Tween 20 (1.0-4.0 wt %), in
      contrast to those emulsions stabilized by beta-conglycinin and glycinin. Langmuir
      Blodgett method and interface pressure determination revealed that LPP formed
      rigid and rough granular film at air/water interface. The excellent stability of
      emulsions stabilized by LPP highlights the synergic effect between hydrophobic
      proteins and phospholipids. These findings suggest that the complexes of
      hydrophobic protein aggregates and biosurfactant could form a stable interface
      which could be developed into a novel strategy to fabricate a stable food
      emulsion.

PMID- 23865497
TI  - Microscopic analysis of sharp force trauma in bone and cartilage: a validation
      study.
AB  - Sharp force trauma research lacks agreement on reported error rates for correctly
      identifying toolmark characteristics on bone and cartilage. This study provides
      error rates for determining blade class (serrated, partially serrated,
      nonserrated) and type of edge bevel (left, right, even). Three analysts examined
      cuts to a wax medium, cartilage, and bone using two types of microscopes.
      Additionally, the observers examined impressions taken from the wax medium and
      the cartilage. Overall, a total of 504 observations were performed. Serrated
      blades were distinguishable from nonserrated blades due to their patterned
      striations. Some difficulties were encountered in distinguishing serrated and
      partially serrated blades; however, when these groups were considered together as
      one classification type (serrated), classification accuracy improved from 79% to
      96%. Classification accuracy for edge bevel was 65%. Error rates were similar
      when comparing direct observation of the cut marks versus indirect observation
      (impressions). Additionally, the type of microscope used did not affect error
      rates. 

PMID- 23865499
TI  - Bioinspired wetting surface via laser microfabrication.
AB  - Bioinspired special wettibilities including superhydrophobicity and tunable
      adhesive force have drawn considerable attention because of their significant
      potential for fundamental research and practical applications. This review
      summarizes recent progress in the development of bioinspired wetting surfaces via
      laser microfabrication, with a focus on controllable, biomimetic, and switchable
      wetting surfaces, as well as their applications in biology, microfluidic, and
      paper-based devices, all of which demonstrate the ability of laser
      microfabrication in producing various multiscale structures and its adaptation in
      a great variety of materials. In particular, compared to other techniques, laser
      microfabrication can realize special modulation ranging from superhydrophilic to
      superhydrophobic without the assistance of fluorination, allowing much more
      freedom to achieve complex multiple-wettability integration. The current
      challenges and future research prospects of this rapidly developing field are
      also being discussed. These approaches open the intriguing possibility of the
      development of advanced interfaces equipped with the integration of more
      functionalities. 

PMID- 23865498
TI  - Genomic characterization provides new insight into Salmonella phage diversity.
AB  - BACKGROUND: Salmonella is a widely distributed foodborne pathogen that causes
      tens of millions of salmonellosis cases globally every year. While the genomic
      diversity of Salmonella is increasingly well studied, our knowledge of Salmonella
      phage genomic diversity is still rather limited, despite the contributions of
      both lysogenic and lytic phages to Salmonella virulence, diversity and ecology
      (e.g., through horizontal gene transfer and Salmonella lysis). To gain a better
      understanding of phage diversity in a specific ecological niche, we sequenced 22
      Salmonella phages isolated from a number of dairy farms from New York State
      (United States) and analyzed them using a comparative genomics approach. RESULTS:
      Classification of the 22 phages according to the presence/absence of orthologous
      genes allowed for classification into 8 well supported clusters. In addition to
      two phage clusters that represent novel virulent Salmonella phages, we also
      identified four phage clusters that each contained previously characterized
      phages from multiple continents. Our analyses also identified two clusters of
      phages that carry putative virulence (e.g., adhesins) and antimicrobial
      resistance (tellurite and bicyclomycin) genes as well as virulent and temperate
      transducing phages. Insights into phage evolution from our analyses include (i)
      identification of DNA metabolism genes that may facilitate nucleotide synthesis
      in phages with a G+C % distinct from Salmonella, and (ii) evidence of Salmonella
      phage tailspike and fiber diversity due to both single nucleotide polymorphisms
      and major re-arrangements, which may affect the host specificity of Salmonella
      phages. CONCLUSIONS: Genomics-based characterization of 22 Salmonella phages
      isolated from dairy farms allowed for identification of a number of novel
      Salmonella phages. While the comparative genomics analyses of these phages
      provide a number of new insights in the evolution and diversity of Salmonella
      phages, they only represent a first glimpse into the diversity of Salmonella
      phages that is likely to be discovered when phages from different environments
      are characterized.

PMID- 23865501
TI  - Small internal jugular veins with restricted outflow are associated with severe
      multiple sclerosis: a sonographer-blinded, case-control ultrasound study.
AB  - BACKGROUND: Recent evidence has indicated an association between chronic
      cerebrospinal venous insufficiency (CCSVI) and multiple sclerosis. Small internal
      jugular veins (IJVs) (with a cross-sectional area of less than 0.4 cm2) have been
      previously described as difficult to catheterize, and their presence may
      potentially affect cerebrospinal venous drainage. In this blinded extracranial
      color-Doppler study we had two principal aims: first, to assess prevalence of
      CCSVI among Serbian MS patients compared to healthy controls; and second, to
      assess prevalence of small IJVs (with a CSA <= 0.4 cm2) among MS patients and
      controls. METHODS: The sixty seven unrelated patients with clinical isolated
      syndrome (CIS), relapsing-remitting (RR), secondary progressive (SP) and primary
      progressive (PP) multiple sclerosis and 21 healthy controls were examined by high
      resolution color-Doppler. RESULTS: The ultrasonographic criteria of CCSVI
      (according to Zamboni) were positive in 11.9% of the patients and in none of the
      control subjects. The CCSVI-positive patients had significantly longer disease
      durations and were significantly more disabled (measured by their Expanded
      Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS)
      scores), but after adjustment for gender and disease duration, CCSVI was not an
      independent risk factor for multiple sclerosis severity. The small IJVs were
      found in 28.4% of the patients and 28.6% of the controls. The patients with small
      IJVs were associated with decreased venous outflow from the brain and presented
      with longer disease durations and significantly higher EDSS and MSSS scores
      compared to patients without small IJVs. A multivariate logistic regression
      analysis adjusted for gender and disease duration showed that small IJV is an
      independent factor associated with multiple sclerosis severity (EDSS >=6)
      (adjusted OR = 8.9, 95% CI: 1.8-45.6, p = 0.007). Among patients with small IJVs
      the 36.84% were also CCSVI positive. CONCLUSIONS: Both, CCSVI and small IJVs seem
      to influence or follow MS severity, but only small IJVs turned out to be an
      independent factor in this study. Thus, small IJVs with restricted outflow, which
      might be aspects of CCSVI different from the criteria originally described by
      Zamboni, emerge as a cofactor in the multifactorial pathophysiology of multiple
      sclerosis.

PMID- 23865502
TI  - On population size estimators in the Poisson mixture model.
AB  - Estimating population sizes via capture-recapture experiments has enormous
      applications. The Poisson mixture model can be adopted for those applications
      with a single list in which individuals appear one or more times. We compare
      several nonparametric estimators, including the Chao estimator, the Zelterman
      estimator, two jackknife estimators and the bootstrap estimator. The target
      parameter of the Chao estimator is a lower bound of the population size. Those of
      the other four estimators are not lower bounds, and they may produce lower
      confidence limits for the population size with poor coverage probabilities. A
      simulation study is reported and two examples are investigated. 

PMID- 23865503
TI  - Ten years of experience in chronic ulcers and malignant transformation.
AB  - Malignant degeneration of wounds is rare and often misdiagnosed. Delay in
      diagnosis may result in a worse prognosis. The aim of this study is to determine
      the number of skin cancers associated with chronic skin ulcers in our facility
      over a period of 10 years. Between January 2002 and December 2012, a total of
      about 1000 patients had consulted with us for chronic wounds, especially of
      vascular, diabetic and traumatic origin and pressure ulcers. Thirteen skin
      cancers had been detected: seven squamous cell and five basal cell carcinomas and
      one melanoma. We highlight how important it is to be aware of the signs
      suggesting a malignant change and the importance of biopsy at regular intervals
      during the life cycle of any chronic wound. 

PMID- 23865504
TI  - Critical size defect regeneration using PEG-mediated BMP-2 gene delivery and the
      use of cell occlusive barrier membranes - the osteopromotive principle revisited.
AB  - OBJECTIVE: The objective of this study was to investigate if osseous regeneration
      can be accelerated by involvement of periosteal tissue. Bone defect regeneration
      could be accelerated by the involvement of periosteal tissue if osteogenic cell
      signalling is maintained within the defect. It was questioned if local cell
      mediated BMP-2 gene delivery makes a cell occlusive membrane dispensable during
      bone critical size defect regeneration. METHODS: PEG matrix (degradation time 10
      days) and PEG membrane (degradation time 120 days) were used in the pig calvarial
      model. Cylindrical (1 * 1 cm) critical size defects (CSD) (9 per animal; 20
      animals) were filled with: (i) particulated autologous bone, covered with PEG
      membrane (group 1); (ii) HA/TCP, covered with PEG membrane (group 2); (iii)
      HA/TCP, mixed with PEG matrix (group 3); and (iv) HA/TCP mixed with BMP-2
      transfected osteoblasts and PEG matrix (group 4). BMP-2/4 gene transfer:
      liposomal in vitro transfection of BMP-2/V5-tag fusion-protein. Quantitative
      histomorphometry (toluidine blue staining) after 2, 4 and 12 weeks assessed bone
      formation. Semiquantitative immunohistochemistry estimated the expression of BMP
      2, V5-tag, Runx-2 and Sox9. RESULTS: PEG matrix embedded BMP-2 expressing cells
      presented higher bone formation (P < 0.05) than HA/TCP + PEG matrix defect
      filling or PEG membrane covering (HA/TCP filling) after 12 weeks. Highest
      expression of BMP-2, Runx-2 and lowest expression of fibrous tissue marker Sox9
      was seen in the BMP-2 group. CONCLUSION: PEG matrix embedded BMP-2 expressing
      cells are capable to maintain osteogenic signalling and to accelerate osseous
      defect regeneration in absence of a cell occlusive membrane.

PMID- 23865506
TI  - The impact of metabolic syndrome, recently diagnosed diabetes and hypertension on
      right ventricular remodeling. Is there difference between risk factors?
AB  - The aim of this study was to compare the right ventricular (RV) structure and
      diastolic function between normotensive and non-diabetic subjects with metabolic
      syndrome (MS), and new diagnosed diabetic and hypertensive patients. Study
      included 89 normotensive and non-diabetic subjects with MS which was defined by
      the presence >=3 ATP-NCEP-III criteria, 45 diabetic and 117 hypertensive
      patients, as well as 76 controls with no MS criteria, matched for age and sex.
      All subjects underwent laboratory blood tests and complete two-dimensional
      echocardiography including pulsed and tissue Doppler. RV free wall thickness was
      similar between MS and diabetic patients, but significantly lower than in
      hypertensive patients (4.6 +/- 0.8 versus 4.3 +/- 0.7 versus 4.9 +/- 0.9 mm; p <
      0.01). Tricuspid E/e' ratio was similar between observed groups (5.3 +/- 1.2
      versus 5.2 +/- 1.1 versus 5.7 +/- 1.2, p > 0.05). RV systolic function evaluated
      by tissue Doppler (st) was similar between MS and diabetic participants, but
      still worse than in hypertensive patients (13.1 +/- 2.2 versus 13.5 +/- 2.5
      versus 12.5 +/- 2.4, p < 0.05). Global RV function estimated by Tei index was
      similar among MS and diabetic patients, and most impaired in hypertensive
      patients (0.47 +/- 0.09 versus 0.45 +/- 0.08 versus 0.52 +/- 0.1, p < 0.01).
      Increased fasting glucose level, abdominal obesity and hypertension were
      independent predictors of biventricular hypertrophy, diastolic dysfunction and
      global dysfunction in whole population. RV structure and function gradually
      deteriorated from diabetic patients, across MS subject, to hypertensive patients.
      Normotensive and non-diabetic subjects with MS had similar level of RV impairment
      as diabetic patients which emphasize the synergic effects of MS components on
      cardiac damage.

PMID- 23865505
TI  - Utility of weekly docetaxel combined with preoperative radiotherapy for locally
      advanced esophageal cancer from pathological analysis.
AB  - Esophageal squamous cell cancer (ESCC) is a high-grade carcinoma that is treated
      with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by
      surgery. Despite some success with these therapies, overall survival remains
      poor. In order to investigate a newer CRT regimen, we designed a comparative
      study to evaluate preoperative CRT using docetaxel (DOC) or 5-Fluorouracil and
      cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a
      retrospective review of patients with resectable, locally advanced ESCC, 95
      patients received preoperative CRT between 2001 and 2007. CRT was administered
      using either FP (n = 40) or DOC (n = 55). Pathological response and clinical
      outcomes were compared between the two groups. Hazard ratios and time-to-event
      analyses were used to assess outcomes; the ratios were controlled by multivariate
      logistic regression analysis of potential prognostic factors, and survival was
      presented with Kaplan-Meier curves. In the FP group, a significant curative
      effect was observed on the basis of pathological examination of postoperative
      lesions. However, the DOC group presented a significantly better prognosis on the
      basis of cumulative survival rates. Logistic regression analysis revealed that
      the presence of five or more lymph node metastases was an independent predictor
      of reduced survival. Patients with lymph node metastasis exhibited a better
      prognosis in the DOC group than those in the FP group. Preoperative CRT for
      locally advanced esophageal cancer using DOC results in similar or better long
      term outcomes compared with FP-based CRT. Therefore, CRT using DOC is a promising
      therapy option for esophageal cancer. 

PMID- 23865507
TI  - Assessment of residual body weight gain and residual intake and body weight gain
      as feed efficiency traits in the turkey (Meleagris gallopavo).
AB  - BACKGROUND: Since feed represents 70% of the total cost in poultry production
      systems, an animal's ability to convert feed is an important trait. In this
      study, residual feed intake (RFI) and residual body weight gain (RG), and their
      linear combination into residual feed intake and body weight gain (RIG) were
      studied to estimate their genetic parameters and analyze the potential
      differences in feed intake between the top ranked birds based on the criteria for
      each trait. METHODS: Phenotypic and genetic analyses were completed on 8340
      growing tom turkeys that were measured for feed intake and body weight gain over
      a four-week period from 16 to 20 weeks of age. RESULTS: The heritabilities of RG
      and RIG were 0.19 +/- 0.03 and 0.23 +/- 0.03, respectively. Residual body weight
      gain had moderate genetic correlations with feed intake (-0.41) and body weight
      gain (0.43). All three linear combinations to form the RIG traits had genetic
      correlations ranging from -0.62 to -0.52 with feed intake, and slightly weaker,
      0.22 to 0.34, with body weight gain. Sorted into three equal groups (low, medium,
      high) based on RG, the most efficient group (high) gained 0.62 and 1.70 kg more
      (P < 0.001) body weight than that of the medium and low groups, yet the feed
      intake for the high group was less (P < 0.05) than that of the medium group
      (19.52 vs. 19.75 kg). When separated into similar partitions, the high RIG group
      (most efficient) had both the lowest (P < 0.001) feed intake (18.86 vs. 19.57 and
      20.41 kg) and the highest (P < 0.001) body weight gain (7.41 vs. 7.03 and 6.43
      kg) relative to the medium and low groups, respectively. CONCLUSIONS: The
      difference in feed intake between the top ranked birds based on different
      residual feed efficiency traits may be small when looking at the average
      individual, however, when extrapolated to the production level, the lower feed
      intake values could lead to significant savings in feed costs over time.

PMID- 23865508
TI  - Triphenylmethane dye activation of beta-arrestin.
AB  - beta-Arrestins regulate G protein-coupled receptor signaling as competitive
      inhibitors and protein adaptors. Low molecular weight biased ligands that bind
      receptors and discriminate between the G protein dependent arm and beta-arrestin,
      clathrin-associated arm of receptor signaling are considered therapeutically
      valuable as a result of this distinctive pharmacological behavior. Other than
      receptor agonists, compounds that activate beta-arrestins are not available. We
      show that within minutes of exposure to the cationic triphenylmethane dyes
      malachite green and brilliant green, tissue culture cells recruit beta-arrestins
      to clathrin scaffolds in a receptor-activation independent manner. In the
      presence of these compounds, G protein signaling is inhibited, ERK and GSK3beta
      signaling are preserved, and the recruitment of the beta2-adaptin, AP2 adaptor
      complex to clathrin as well as transferrin internalization is reduced. Moreover,
      malachite green binds beta-arrestin2-GFP coated immunotrap beads relative to GFP
      only coated beads. Triphenylmethane dyes are FDA approved for topical use on
      newborns as components of triple-dye preparations and are not approved but used
      effectively as aqueous antibiotics in fish husbandry. As possible carcinogens,
      their chronic ingestion in food preparations, particularly through farmed fish,
      is discouraged in the U.S. and Europe. Our results indicate triphenylmethane dyes
      as a result of novel pharmacology may have additional roles as beta
      arrestin/clathrin pathway signaling modulators in both pharmacology research and
      clinical therapy. 

PMID- 23865509
TI  - The "Health Coaching" programme: a new patient-centred and visually supported
      approach for health behaviour change in primary care.
AB  - BACKGROUND: Health related behaviour is an important determinant of chronic
      disease, with a high impact on public health. Motivating and assisting people to
      change their unfavourable health behaviour is thus a major challenge for health
      professionals. The objective of the study was to develop a structured programme
      of counselling in primary care practice, and to test its feasibility and
      acceptance among general practitioners (GPs) and their patients. METHODS: Our new
      concept integrates change of roles, shared responsibility, patient-centredness,
      and modern communication techniques-such as motivational interviewing. A new
      colour-coded visual communication tool is used for the purpose of leading through
      the 4-step counselling process. As doctors' communication skills are crucial,
      communication training is a mandatory part of the programme. We tested the
      feasibility and acceptance of the "Health Coaching" programme with 20 GPs and
      1045 patients, using questionnaires and semistructured interviewing techniques.
      The main outcomes were participation rates; the duration of counselling;
      patients' self-rated behavioural change in their areas of choice; and ratings of
      motivational, conceptual, acceptance, and feasibility issues. RESULTS: In total,
      37% (n=350) of the patients enrolled in step 1 completed the entire 4-Step
      counselling process, with each step taking 8-22 minutes. 50% of ratings (n=303)
      improved by one or two categories in the three-colour circle, and the proportion
      of favourable health behaviour ratings increased from 9% to 39%. The ratings for
      motivation, concept, acceptance, and feasibility of the "Health Coaching"
      programme were consistently high. CONCLUSIONS: Our innovative, patient-centred
      counselling programme for health behaviour change was well accepted and feasible
      among patients and physicians in a primary care setting. Randomised controlled
      studies will have to establish cost-effectiveness and promote dissemination.

PMID- 23865510
TI  - A descriptive exploration of the experiences of patients with significant
      functional impairment following a recent diagnosis of metastatic spinal cord
      compression.
AB  - AIM: To explore the experiences, concerns and priorities of patients newly
      diagnosed with advanced malignant spinal cord compression and had significant
      problems with mobility at presentation. BACKGROUND: The consequences of malignant
      spinal cord compression can be devastating. Patients and their families are under
      pressure to adapt quickly to the significant functional impairment that occurs
      while coping with a diagnosis of advanced cancer. Much of the literature has
      focused on diagnosis and treatment and little is known about patients'
      experiences, priorities and concerns. DESIGN: A descriptive qualitative
      methodology was adopted using semi-structured interviews and Framework Analysis
      techniques. METHOD: A semi-structured interview schedule was developed to explore
      patient's descriptions of their experiences leading up to diagnosis and during
      their admission to the cancer centre along with their thoughts and feelings about
      their future with malignant spinal cord compression. The interviews took place
      after completion of radiotherapy before discharge home. Interviews were carried
      out between April 2009-March 2010. FINDINGS: Ten participants were interviewed. A
      dual narrative was identified in which participants talked about their concerns
      and emphasized their ability to cope and maintain a positive outlook. Patients'
      concerns and priorities were identified. Maintaining hope emerged as an important
      element of coping. Uncertainty was a source of hope. CONCLUSION: The study
      provides insights into the experience of malignant spinal cord compression from
      symptom occurrence to diagnosis and beyond. The findings highlight the importance
      of early discharge planning and family involvement in meeting patients'
      priorities for care.

PMID- 23865511
TI  - The effect of synthetic method and annealing temperature on metal site preference
      in Al(1-x)Ga(x)FeO3.
AB  - Magnetoelectric materials couple both magnetic and electronic properties, making
      them attractive for use in multifunctional devices. The magnetoelectric AFeO3
      compounds (Pna2(1); A = Al, Ga) have received attention as the properties of the
      system depend on composition as well as the synthetic method used. Al(1
      x)Ga(x)FeO3. (0 <= x <= 1) was synthesized by the sol-gel and coprecipitation
      methods and studied by X-ray absorption near-edge spectroscopy (XANES). Al L(2,3
      ), Ga K-, and Fe K-edge XANES spectra were collected to examine how the average
      metal coordination number (CN) changes with the synthetic method. Al and Fe were
      found to prefer octahedral sites, while Ga prefers the tetrahedral site. It was
      found that composition played a larger role in determining site occupancies than
      synthetic method. Samples made by the sol-gel or ceramic methods (reported
      previously; Walker, J. D. S.; Grosvenor, A. P. J. Solid State Chem. 2013, 197,
      147-153) showed smaller spectral changes than samples made via the
      coprecipitation method. This is attributed to greater ion mobility in samples
      synthesized via coprecipitation as the reactants do not have a long-range
      polymeric or oxide network during synthesis like samples synthesized via the sol
      gel or ceramic method. Increasing annealing temperature increases the average
      coordination number of Al, and to a lesser extent Ga, while the average
      coordination number of Fe decreases. This study indicates that greater disorder
      is observed when the Al(1-x)Ga(x)FeO3. compounds have high Al content, and when
      annealed at higher temperatures.

PMID- 23865512
TI  - Auricular acupressure for analgesia in perioperative period of total knee
      arthroplasty.
AB  - OBJECTIVE: We examined whether auricular acupressure (AA) can alleviate
      postoperative pain and decrease narcotic consumption and its adverse effects for
      osteoarthritis patients after total knee arthroplasty (TKA). DESIGN: A
      prospective, randomized, sham control trial comparing AA and a sham control.
      SETTING: Department of Orthopedics, the first Hospital affiliated to Zhejiang
      University of Traditional Chinese Medicine, Hangzhou, China. SUBJECTS: Ninety
      patients with degenerative osteoarthritis undergoing TKA. INTERVENTIONS: The AA
      group received true AA by embedding vaccaria seeds at four specific AA points
      (knee joint, shenmen, subcortex, sympathesis) ipsilateral to the surgery site,
      while the control group received four nonacupuncture points on the auricular
      helix. OUTCOME MEASURES: Visual analog scale (VAS), the consumption of analgesic
      via patient-controlled analgesia, the incidence of analgesia-related adverse
      effects, Hospital for Special Surgery scores (HSS), and range of motion (ROM)
      were recorded. RESULTS: VAS scores were similar at 12, 24, 36, and 48 h
      postsurgery (P > 0.05), but AA group scores were lower than those of the control
      group at 3, 4, 5, and 7 days (P < 0.05). Patients in the AA group consumed lower
      doses of analgesic than those in the control group after surgery (P < 0.05). The
      incidence of analgesia-related adverse effects in the AA group was lower than
      that in the control group (P < 0.05). Although HSS scores were similar in the two
      groups preoperatively and at 3 months postoperatively (P > 0.05), HSS scores 2
      weeks postoperatively were higher in the AA group than in the control group (P <
      0.05), but there was no difference between groups in ROM (P > 0.05). CONCLUSIONS:
      Applying auricular acupoint acupressure in the perioperative period of TKA is
      favorable for alleviating postoperative pain, decreasing opioid consumption and
      its adverse effects, and promoting early rehabilitation. Also, this intervention
      has the advantage of lower costs, fewer complications, simple application, and
      high safety.

PMID- 23865513
TI  - Experiences of non-resident nurses in Australia's remote Northern Territory.
AB  - INTRODUCTION: There is emerging concern in the health literature about the
      impacts of non-resident work modes on the quality of service delivery
      particularly in sparsely populated or remote areas, but little is known about
      what non-resident health workers themselves see as the advantages and
      disadvantages of their modes of work, and whether non-resident workers face the
      same or different social/personal and professional barriers to rural and remote
      practice as their resident colleagues. Although literature from the resources
      sector provides insights into the expected social/personal advantages and
      disadvantages, very little is said about professional issues. METHODS: This
      article reports on semi-structured interviews conducted with seven non-resident
      nurses working in remote locations in Australia's Northern Territory in 2011. All
      nurses lived outside the Northern Territory when not at work. The interviews
      focussed on how the separation of place of residence and place of work affected
      nurses' private and professional lives. RESULTS: Social/personal issues faced by
      these nurses are similar to what has been reported in the broader literature on
      non-resident work. Nurses who successfully engage in non-resident work develop
      strategies to manage their lives across multiple locations. However, questions
      are raised about the professional impacts of non-resident work, in terms of the
      continuing competency of the workers themselves, the performance of work teams
      that consist of resident and non-resident workers, and the maintenance of context
      specific skills. CONCLUSIONS: Non-resident work is likely to become more common
      in remote areas such as Australia's Northern Territory because of the advantages
      workers experience in their personal lives. There is an urgent need to address
      professional issues associated with non-resident work modes.

PMID- 23865514
TI  - Theoretical study on the gas phase reaction of allyl alcohol with hydroxyl
      radical.
AB  - The complex potential energy surface of allyl alcohol (CH2CHCH2OH) with hydroxyl
      radical (OH) has been investigated at the G3(MP2)//MP2/6-311++G(d,p) level. On
      the surface, two kinds of pathways are revealed, namely, direct hydrogen
      abstraction and addition/elimination. Rice-Ramsperger-Kassel-Marcus theory and
      transition state theory are carried out to calculate the total and individual
      rate constants over a wide temperature and pressure region with tunneling
      correction. It is predicted that CH2CHOHCH2OH (IM1) formed by collisional
      stabilization is dominate in the temperature range (200-440 K) at atmospheric
      pressure with N2 (200-315 K at 10 Torr Ar and 100 Torr He). The production of
      CH2CHCHOH + H2O via direct hydrogen abstraction becomes dominate at higher
      temperature. The kinetic isotope effect (KIE) has also been calculated for the
      title reaction. Moreover, the calculated rate constants and KIE are in good
      agreement with the experimental data. 

PMID- 23865515
TI  - Comparison of outcomes of twins conceived spontaneously and by artificial
      reproductive therapy.
AB  - OBJECTIVE: To compare the outcomes of twin pregnancies conceived by artificial
      reproductive techniques (ART) with those of spontaneous conception. STUDY DESIGN:
      In this multicenter prospective trial, comparisons were made between methods of
      conception in twin pregnancies, for maternal and perinatal outcomes. RESULTS: Of
      1001 twin pairs, 763/1001 (72.7%) were spontaneously conceived and
      238/1001(27.3%) were conceived by ART. There were no significant differences
      between the two groups with respect to obstetric complications. There were 13 per
      1000 (20/1504; 1%) perinatal deaths in the spontaneously conceived group and 6
      per 1000 (3/466; 0.6%) in the ART group (p = 0.8141). We found no differences in
      gestational age at delivery (median 36.9 versus 37.0 weeks), birth weight (median
      2520 g versus 2538 g), or in a composite measure of adverse perinatal outcome
      (17% versus 15%) between the groups. CONCLUSION: There were no differences in the
      rate of adverse obstetric or perinatal outcomes between twins conceived naturally
      compared with twins conceived by assisted conception.

PMID- 23865516
TI  - Acute biomarkers of traumatic brain injury: relationship between plasma levels of
      ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein.
AB  - Biomarkers are important for accurate diagnosis of complex disorders such as
      traumatic brain injury (TBI). For a complex and multifaceted condition such as
      TBI, it is likely that a single biomarker will not reflect the full spectrum of
      the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH
      L1) and glial fibrillary acidic protein (GFAP) are among of the most widely
      studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular
      events, we hypothesized that analysis of both biomarkers would be superior to
      analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of
      UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a
      multicenter observational study (Transforming Research and Clinical Knowledge in
      Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly
      correlated to each other (r=0.364). Each biomarker in isolation had good
      sensitivity and sensitivity for discriminating between TBI patients and healthy
      controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP,
      respectively). When biomarkers were combined, superior sensitivity and
      specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers
      discriminated between TBI patients with intracranial lesions on CT scan and those
      without such lesions, but GFAP measures were significantly more sensitive and
      specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months
      after injury, neither biomarker had adequate sensitivity and specificity (AUC
      0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome
      Scale Extended [GOS-E] threshold used). Our results support a role for multiple
      biomarker measurements in TBI research. ( ClinicalTrials.gov Identifier
      NCT01565551).

PMID- 23865517
TI  - Rapid exploration of configuration space with diffusion-map-directed molecular
      dynamics.
AB  - The gap between the time scale of interesting behavior in macromolecular systems
      and that which our computational resources can afford often limits molecular
      dynamics (MD) from understanding experimental results and predicting what is
      inaccessible in experiments. In this paper, we introduce a new sampling scheme,
      named diffusion-map-directed MD (DM-d-MD), to rapidly explore molecular
      configuration space. The method uses a diffusion map to guide MD on the fly. DM-d
      MD can be combined with other methods to reconstruct the equilibrium free energy,
      and here, we used umbrella sampling as an example. We present results from two
      systems: alanine dipeptide and alanine-12. In both systems, we gain tremendous
      speedup with respect to standard MD both in exploring the configuration space and
      reconstructing the equilibrium distribution. In particular, we obtain 3 orders of
      magnitude of speedup over standard MD in the exploration of the configurational
      space of alanine-12 at 300 K with DM-d-MD. The method is reaction coordinate free
      and minimally dependent on a priori knowledge of the system. We expect wide
      applications of DM-d-MD to other macromolecular systems in which equilibrium
      sampling is not affordable by standard MD. 

PMID- 23865518
TI  - Hyperoxic condition promotes an inflammatory response during cardiopulmonary
      bypass in a rat model.
AB  - Systemic inflammatory responses in patients receiving cardiac surgery supported
      by cardiopulmonary bypass (CPB) significantly contribute to CPB-associated
      morbidity and mortality. We hypothesized that hyperoxia insufflation aggravates
      the inflammatory responses and organ damage during CPB. To verify this
      hypothesis, we investigated the inflammatory responses at high and normal levels
      of arterial pressure of oxygen (PaO2 ) in the rat CPB model. Rats were divided
      into a SHAM group, a hyperoxia CPB group (PaO2  > 400 mm Hg), and a normoxia CPB
      group (PaO2 : 100-150 mm Hg). We measured the serum cytokine levels of tumor
      necrosis factor-alpha, interleukin (IL)-6, and IL-10, and biochemical markers
      (lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase)
      before, 60, and 120 min after the initiation of CPB. We also measured the wet-to
      dry weight (W/D) ratio of the left lung and performed dihydroethidium (DHE) stain
      reflecting superoxide generation in the lung and liver tissues 120 min after the
      CPB initiation. In the hyperoxia group, the pro-inflammatory cytokines and
      biochemical markers significantly increased during the CPB compared with the
      SHAM, but such increases were significantly suppressed in the normoxia group.
      However, the increase in anti-inflammatory cytokines was more suppressed in the
      hyperoxia group than in the normoxia group. The W/D ratio increased significantly
      more in the hyperoxia group than in the normoxia group. In addition, the DHE
      fluorescence predominantly increased in the hyperoxia group compared with that in
      the normoxia group. These data suggest that it is better to avoid too much oxygen
      insufflation for attenuating organ damage associated with the superoxide
      production and inflammatory responses during CPB.

PMID- 23865519
TI  - Discovery and characterization of miRNA genes in Atlantic salmon (Salmo salar) by
      use of a deep sequencing approach.
AB  - BACKGROUND: MicroRNAs (miRNAs) are an abundant class of endogenous small RNA
      molecules that downregulate gene expression at the posttranscriptional level.
      They play important roles in multiple biological processes by regulating genes
      that control developmental timing, growth, stem cell division and apoptosis by
      binding to the mRNA of target genes. Despite the position Atlantic salmon (Salmo
      salar) has as an economically important domesticated animal, there has been
      little research on miRNAs in this species. Knowledge about miRNAs and their
      target genes may be used to control health and to improve performance of
      economically important traits. However, before their biological function can be
      unravelled they must be identified and annotated. The aims of this study were to
      identify and characterize miRNA genes in Atlantic salmon by deep sequencing
      analysis of small RNA libraries from nine different tissues. RESULTS: A total of
      180 distinct mature miRNAs belonging to 106 families of evolutionary conserved
      miRNAs, and 13 distinct novel mature miRNAs were discovered and characterized.
      The mature miRNAs corresponded to 521 putative precursor sequences located at
      unique genome locations. About 40% of these precursors were part of gene
      clusters, and the majority of the Salmo salar gene clusters discovered were
      conserved across species. Comparison of expression levels in samples from
      different tissues applying DESeq indicated that there were tissue specific
      expression differences in three conserved and one novel miRNA. Ssa-miR 736 was
      detected in heart tissue only, while two other clustered miRNAs (ssa-miR 212
      and132) seems to be at a higher expression level in brain tissue. These
      observations correlate well with their expected functions as regulators of signal
      pathways in cardiac and neuronal cells, respectively. Ssa-miR 8163 is one of the
      novel miRNAs discovered and its function remains unknown. However, differential
      expression analysis using DESeq suggests that this miRNA is enriched in liver
      tissue and the precursor was mapped to intron 7 of the transferrin gene.
      CONCLUSIONS: The identification and annotation of evolutionary conserved and
      novel Salmo salar miRNAs as well as the characterization of miRNA gene clusters
      provide biological knowledge that will greatly facilitate further functional
      studies on miRNAs in this species.

PMID- 23865521
TI  - Anti-salusin-beta antibody enhances angiogenesis after myocardial ischemia
      reperfusion injury.
AB  - BACKGROUNDS: Salusins are multifunctional endogenous bioactive peptides
      simultaneously biosynthesized from their precursor prosalusin. Salusin-beta
      stimulates proliferation of vascular smooth muscle cells and fibroblasts and
      regulates myocardial growth and hypertrophy. Salusin-beta has potent hypotensive,
      bradycardic and proatherosclerotic effects. OBJECTIVES: To investigate whether
      salusin-beta plays a role in myocardial remodeling after myocardial ischemia
      reperfusion (I/R) injury, rat I/R models were created by the left anterior
      descending coronary artery occlusion for 30 min, followed by 24 h or 7 days of
      reperfusion (control, n = 6 each). RESULTS AND CONCLUSION: Immunohistochemical
      double staining showed the enhanced expression of salusin-beta in the macrophages
      around myocardial ischemic area. Anti-salusin-beta treated groups were
      administered the neutralizing salusin-beta antibody (10 MUl/day, i.p.) once daily
      from day -1 to day 1 or from day -1 to day 7 (anti-salusin-beta, n = 6 each). The
      anti-salusin-beta therapy enhanced myocardial angiogenesis in the peri-ischemic
      area of reperfusion. The small vessels (< 40 MUm in diameter) of I/R hearts
      treated with anti-salusin-beta were more densely populated than those of control
      animals (108.5 +/- 19.7 vs 47.5 +/- 2.4, p < 0.05). Real-time PCR revealed that
      the anti-salusin-beta therapy-induced angiogenesis was not associated with
      enhanced vascular endothelial growth factor A expression. The authors, for the
      first time, have clarified that endogenous salusin-beta suppresses angiogenesis
      which is critical in the development of cardiac remodeling following I/R injury.

PMID- 23865520
TI  - The role of CD133+ cells in a recurrent embryonal tumor with abundant neuropil
      and true rosettes (ETANTR).
AB  - Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a recently
      described embryonal neoplasm of the central nervous system, consisting of a well
      circumscribed embryonal tumor of infancy with mixed features of ependymoblastoma
      (multilayer ependymoblastic rosettes and pseudorosettes) and neuroblastoma
      (neuroblastic rosettes) in the presence of neuropil-like islands. We present the
      case of a young child with a very aggressive tumor that rapidly recurred after
      gross total resection, chemotherapy and radiation. Prominent vascular sclerosis
      and circumscribed tumor led to the diagnosis of malignant astroblastoma; however,
      rapid recurrence and progression of this large tumor after gross total resection
      prompted review of the original pathology. ETANTR is histologically distinct with
      focal glial fibrillary acid protein (GFAP) and synaptophysin expression in the
      presence of neuronal and ependymoblastic rosettes with focal neuropil islands.
      These architectural features, combined with unique chromosome 19q13.42
      amplification, confirmed the diagnosis. In this report, we describe tumor stem
      cell (TSC) marker CD133, CD15 and nestin alterations in ETANTR before and after
      chemotherapy. We found that TSC marker CD133 was richly expressed after
      chemotherapy in recurrent ETANTR, while CD15 is depleted compared with that
      expressed in the original tumor, suggesting that CD133+ cells likely survived
      initial treatment, further contributing to formation of the recurrent tumor. 

PMID- 23865522
TI  - Calcium-binding capacity of wheat germ protein hydrolysate and characterization
      of Peptide-calcium complex.
AB  - This study investigates the ability of various wheat germ protein hydrolysates
      (WGPHs) to bind calcium and characterizes the peptide-calcium complexes. We
      demonstrate that the amount of Ca bound depended greatly on the type of enzyme,
      degree of hydrolysis (DH), amino acid composition, and molecular mass
      distribution of different hydrolysates. The maximum level of Ca bound (67.5 mg.g(
      1)) occurred when Alcalase was used to hydrolyze wheat germ protein at a DH of
      21.5%. Peptide fragments exhibiting high calcium-binding capacity had molecular
      mass <2000 Da. The calcium-binding peptides mainly consisted of Glu, Arg, Asp,
      and Gly, and the level of Ca bound was related to the hydrophobic amino acid
      content in WGPHs. UV-visible and Fourier transform infrared spectra demonstrate
      that amino nitrogen atoms and oxygen atoms on the carboxyl group were involved in
      complexation. Therefore, wheat germ protein is a promising protein source for the
      production of calcium-binding peptides and could be utilized as a bioactive
      ingredient for nutraceutical food production. 

PMID- 23865523
TI  - Dynamic pseudo-observations: a robust approach to dynamic prediction in competing
      risks.
AB  - In this article, we propose a new approach to the problem of dynamic prediction
      of survival data in the presence of competing risks as an extension of the
      landmark model for ordinary survival data. The key feature of our method is the
      introduction of dynamic pseudo-observations constructed from the prediction
      probabilities at different landmark prediction times. They specifically address
      the issue of estimating covariate effects directly on the cumulative incidence
      scale in competing risks. A flexible generalized linear model based on these
      dynamic pseudo-observations and a generalized estimation equations approach to
      estimate the baseline and covariate effects will result in the desired dynamic
      predictions and robust standard errors. Our approach has a number of attractive
      features. It focuses directly on the prediction probabilities of interest,
      avoiding in this way complex modeling of cause-specific hazards or
      subdistribution hazards. As a result, it is robust against departures from these
      omnibus models. From a computational point of view an advantage of our approach
      is that it can be fitted with existing statistical software and that a variety of
      link functions and regression models can be considered, once the dynamic pseudo
      observations have been estimated. We illustrate our approach on a real data set
      of chronic myeloid leukemia patients after bone marrow transplantation. 

PMID- 23865524
TI  - Highly ordered protein nanorings designed by accurate control of glutathione S
      transferase self-assembly.
AB  - Protein self-assembly into exquisite, complex, yet highly ordered architectures
      represents the supreme wisdom of nature. However, precise manipulation of protein
      self-assembly behavior in vitro is a great challenge. Here we report that by
      taking advantage of the cooperation of metal-ion-chelating interactions and
      nonspecific protein-protein interactions, we achieved accurate control of the
      orientation of proteins and their self-assembly into protein nanorings. As a
      building block, we utilized the C2-symmetric protein sjGST-2His, a variant of
      glutathione S-transferase from Schistosoma japonicum having two properly oriented
      His metal-chelating sites on the surface. Through synergic metal-coordination and
      non-covalent interactions, sjGST-2His self-assembled in a fixed bending manner to
      form highly ordered protein nanorings. The diameters of the nanorings can be
      regulated by tuning the strength of the non-covalent interaction network between
      sjGST-2His interfaces through variation of the ionic strength of the solution.
      This work provides a de novo design strategy that can be applied in the
      construction of novel protein superstructures. 

PMID- 23865525
TI  - Application of infrared and Raman spectroscopy in paint trace examination.
AB  - Raman spectroscopy has proved to be a promising technique in forensic
      examinations, where optical microscopy, micro-infrared spectroscopy, and
      microspectrophotometry in the visible and UV range are used for identification
      and differentiation between paint traces. Often no organic pigments are detected
      using Fourier transform infrared spectroscopy, because their content in a trace
      is usually undetectable. Application of a micro-Raman spectrometer equipped with
      several excitation lasers helps forensic experts in paint analysis enabling
      identification of main pigments. Three cases concerning comparative examination
      of car paint are discussed in detail. The comparison of Raman spectra of paint
      chips found on clothing of a victim or smears found on body of a damaged car to
      these of paint chips originated from the suspected car enabled us to identify the
      car involved in the accident. When no comparative material is available, the
      method can be useful in establishing the color and make of the car. 

PMID- 23865527
TI  - Insertion of reactive rhodium carbenes into boron-hydrogen bonds of stable N
      heterocyclic carbene boranes.
AB  - Readily available rhodium(II) salts catalyze reactions between NHC-boranes (NHC
      BH3) and diazocarbonyl compounds (N2CRCOR'). Stable alpha-NHC-boryl carbonyl
      compounds (NHC-BH2-CHRCOR') are isolated in good yields. The reaction is a
      reliable way to make boron-carbon bonds with good tolerance for variation in both
      the NHC-borane and diazocarbonyl components. It presumably occurs by insertion of
      a transient rhodium carbene into a boron-hydrogen bond of the NHC-borane.
      Competitive experiments show that a typical NHC-borane is highly reactive toward
      rhodium carbenes. 

PMID- 23865526
TI  - Is a hypothetical melanoma-like neuromelanin the underlying factor essential for
      the aetiopathogenesis and clinical manifestations of multiple sclerosis?
AB  - BACKGROUND: Multiple sclerosis (MS) has undergone a significant increase in
      incidence in the industrialised nations over the last 130 years. Changing
      environmental factors, possibly infections or a lack of or altered timing of
      them, determine the prevalence of the disease. Although a plethora of
      aetiological factors, clearly evident in a group of children with MS, appear
      relevant, there may nevertheless be a single factor essential for the
      aetiopathogenesis and clinical manifestation of MS. DESCRIPTION AND DISCUSSION:
      This hitherto unknown factor is postulated to be a 'melanoma-like neuromelanin'
      (MLN) dependent on the activation of a gene for syncytin-1. An involvement of MLN
      could explain the diverse findings in the epidemiology, immunology and pathology
      of MS, requiring a consideration of a complex infectious background, the human
      leucocyte antigens, as well as cosmic radiation causing geomagnetic disturbances,
      vitamin D deficiency, smoking, and lower levels of uric acid. SUMMARY: In
      principle, the MLN-based concept is a unifying one, capable of explaining a
      number of characteristics of the disease. To date, MLN has not been addressed in
      studies on MS and future work will need to be done on human patients, as there is
      little or no neuromelanin (the precursor of MLN) in the animals used as
      experimental models in the study of MS.

PMID- 23865529
TI  - Convenient, attractive, and normative: the CAN approach to making children slim
      by design.

PMID- 23865528
TI  - Evaluation of a community-based weight management program for predominantly
      severely obese, difficult-to-reach, inner-city minority adolescents.
AB  - BACKGROUND: Few interventions targeting severely obese minority youth have been
      implemented in community-based settings. We evaluate a 9-month multicomponent,
      community-based program for obese, inner-city adolescents. METHODS: Of 5250
      estimated eligible adolescents, 349 were recruited; they had a mean age of 15 +/-
      2 years, mean BMI %ile 98.9 +/- 1.5, and comprised 52% African American and 44%
      Hispanic. Longitudinal trends of anthropometric measures were compared 1 year
      before enrollment (T-12), at baseline (T0) and after program completion (T9).
      Dietary and physical activity behaviors were compared at T0 and T9.
      Anthropometric changes were compared at T9 and 18 months (T18) in completers and
      noncompleters. RESULTS: A majority of participants were severely obese (67%) and
      expressed low readiness to change behaviors (82%). For intervals T-12 to T0
      versus T0 to T9, there were significant decreases in rates of gain in BMI (0.13
      vs. 0.04, p < 0.01), BMI percentile (0.0002 vs. -0.0001, p < 0.01), percent
      overweight (0.001 vs. -0.001, p < 0.01), and BMI z-score (0.003 vs. -0.003, p <
      0.01). Significant increases in vegetable and fruit consumption and in vigorous
      physical activity participation were observed. From T9 to T18, except for a
      significant increase in BMI (38.3 +/- 7.4 vs. 39.0 +/- 7.5, p < 0.01) in
      completers, all other anthropometric measures remained unchanged in completers
      and noncompleters. CONCLUSIONS: We demonstrate modest clinical improvements and
      increased healthy lifestyle behaviors in predominantly severely obese, difficult
      to-reach, ethnic minority adolescents attending a community-based weight
      management program. The loss of clinical improvements 9 months after program
      completion implies that extending the duration of such a program may prevent long
      term weight regain in severely obese adolescents.

PMID- 23865530
TI  - The Philadelphia experience: actionable strategies for childhood obesity
      prevention.

PMID- 23865534
TI  - Use of isothermal microcalorimetry to quantify the influence of glucose and
      antifungals on the growth of Candida albicans in urine.
AB  - AIMS: Urinary tract infection (UTI) caused by Candida spp. is an increasing
      problem in clinical practice. Risk factors include diabetes mellitus, extremes of
      age, urinary tract abnormalities and indwelling catheters. Here, we determined
      the applicability of isothermal microcalorimetry (IMC) for the detection and
      antifungal drug susceptibility testing of Candida albicans in artificial urine.
      METHODS AND RESULTS: Isothermal microcalorimetry was used to monitor the
      metabolic heat production rates of C. albicans at 37  degrees C (MUW = MUJ s(-1)
      ). The influence of increasing concentrations of glucose and antifungal drugs on
      the growth of C. albicans was investigated. The growth rate increased linearly
      from 0.024 +/- 0.010 to 0.203 +/- 0.006 h(-1) with increasing concentration of
      glucose from 20 to 1640 mg l(-1) . The minimum inhibitory concentrations (MIC)
      against C. albicans were determined at a fixed glucose concentration of 560 mg l(
      1) . These MIC were 0.5 MUg ml(-1) for amphotericin B, 5 MUg ml(-1) for
      flucytosine, 0.8 MUg ml(-1) for fluconazole and 0.5 MUg ml(-1) for tioconazole,
      respectively. CONCLUSIONS: IMC is able to detect and quantify growth of C.
      albicans in artificial urine and to determine the MIC of antifungal drugs against
      C. albicans. This study demonstrated that IMC can be used for basic research on
      Candida-UTI and opens promising avenue for the use of IMC as rapid drug
      resistance screening tool and diagnostic tool. SIGNIFICANCE AND IMPACT OF STUDY:
      Little is known on the growth of C. albicans in urine. Our study provides
      measurements of the growth rate of this yeast in urine with various glucose
      concentrations. Thus, important insights are gathered for risk group such as
      patients with diabetes or patients with prolonged parenteral nutrition resulting
      in higher urinary glucose concentration.

PMID- 23865535
TI  - Block copolymer hollow fiber membranes with catalytic activity and pH-response.
AB  - We fabricated block copolymer hollow fiber membranes with self-assembled, shell
      side, uniform pore structures. The fibers in these membranes combined pores able
      to respond to pH and acting as chemical gates that opened above pH 4, and
      catalytic activity, achieved by the incorporation of gold nanoparticles. We used
      a dry/wet spinning process to produce the asymmetric hollow fibers and determined
      the conditions under which the hollow fibers were optimized to create the desired
      pore morphology and the necessary mechanical stability. To induce ordered micelle
      assembly in the doped solution, we identified an ideal solvent mixture as
      confirmed by small-angle X-ray scattering. We then reduced p-nitrophenol with a
      gold-loaded fiber to confirm the catalytic performance of the membranes. 

PMID- 23865536
TI  - Enzyme inhibition-based determination of pesticide residues in vegetable and soil
      in centrifugal microfluidic devices.
AB  - Pesticide residue is of concern as an environmental pollutant when present at
      medium to high concentrations. Such residue was quantified in both vegetable and
      soil samples by an enzyme inhibition technique. The multistep reactions were
      integrated into centrifugal microfluidic devices allowing automated simultaneous
      analysis of several samples or of replicates. The small sample size inherent to
      microfluidic devices allowed for less reagent to be used including less of the
      expensive enzyme which is key to this method. Liquid-solid magnetically actuated
      extraction, filtration, sedimentation, and detection were all integrated on the
      same device. Several parameters were optimized including the concentration of
      enzyme, substrate, chromatic agent, and reaction time. In this environmental
      application of centrifugal microfluidics, the percent inhibition of enzyme
      activity is logarithmically proportional to the demonstration pesticide
      concentration (in this case carbofuran). This meant that as the pesticide
      concentration increased in the samples, the reaction was more inhibited and the
      final product absorbed less light at 525 nm. Two versions of the centrifugal
      microfluidic devices were made. One version was designed for the analysis of
      vegetable samples (cabbage) and the other for the analysis of soil samples. Each
      version provided results that were statistically similar to the conventional
      benchtop method with a carbofuran limit of detection of 0.1 ppm or 0.1 MUg g(-1)
      (5 ng absolute limit of detection). 

PMID- 23865538
TI  - Profound isotope effect in dissociation of triatomic hydrogen.
AB  - Three-particle dissociation of high-lying Rydberg states of D3 is induced by an
      external electric field. We observe that the momentum vector correlation map of
      the center-of-mass motion of the fragments converges near the ionization
      threshold to two distinct fragment configurations, the near linear geometry and
      the symmetric acute angle geometry. A comparison is made with the momentum vector
      correlation map recorded in dissociative recombination of D3(+) with slow
      electrons and with the corresponding results for H3 where the acute angle
      geometry is conspicuously absent.

PMID- 23865537
TI  - Designing a complex intervention for dementia case management in primary care.
AB  - BACKGROUND: Community-based support will become increasingly important for people
      with dementia, but currently services are fragmented and the quality of care is
      variable. Case management is a popular approach to care co-ordination, but
      evidence to date on its effectiveness in dementia has been equivocal. Case
      management interventions need to be designed to overcome obstacles to care co
      ordination and maximise benefit. A successful case management methodology was
      adapted from the United States (US) version for use in English primary care, with
      a view to a definitive trial. Medical Research Council guidance on the
      development of complex interventions was implemented in the adaptation process,
      to capture the skill sets, person characteristics and learning needs of primary
      care based case managers. METHODS: Co-design of the case manager role in a single
      NHS provider organisation, with external peer review by professionals and carers,
      in an iterative technology development process. RESULTS: The generic skills and
      personal attributes were described for practice nurses taking up the case manager
      role in their workplaces, and for social workers seconded to general practice
      teams, together with a method of assessing their learning needs. A manual of
      information material for people with dementia and their family carers was also
      created using the US intervention as its source. CONCLUSIONS: Co-design produces
      rich products that have face validity and map onto the complexities of dementia
      and of health and care services. The feasibility of the case manager role, as
      described and defined by this process, needs evaluation in 'real life' settings.

PMID- 23865539
TI  - Chemotherapeutic options for colorectal cancer patients with cardiovascular
      diseases.
AB  - The high incidence of cardiovascular disease and colorectal cancer in the world's
      population means that these two conditions may coexist in the same patient. In
      addition fluoropyrimidines, backbone for the treatment of colorectal cancer in
      both early stage and advanced disease, have a well-characterized cardio-toxicity,
      which limits their use in patients with heart disease and limits their
      reintroduction in those patients who have shown this toxicity. For the treatment
      of this, increasing proportion of patients is now possible to consider
      fluoropyrimidines-free chemotherapy regimens that are examined in this work, with
      the attempt to provide a possible treatment algorithm for various situations
      encountered in clinical practice. 

PMID- 23865541
TI  - The promises and pitfalls of leveraging mobile health technology for pain care.

PMID- 23865542
TI  - Antioxidants for chronic kidney disease.

PMID- 23865540
TI  - The IL-10 homologue encoded by cyprinid herpesvirus 3 is essential neither for
      viral replication in vitro nor for virulence in vivo.
AB  - Cyprinid herpesvirus 3 (CyHV-3), a member of the family Alloherpesviridae, is the
      causative agent of a lethal disease in common and koi carp. CyHV-3 ORF134 encodes
      an interleukin-10 (IL-10) homologue. The present study was devoted to this ORF.
      Transcriptomic analyses revealed that ORF134 is expressed as a spliced gene
      belonging to the early-late class. Proteomic analyses of CyHV-3 infected cell
      supernatant demonstrated that the ORF134 expression product is one of the most
      abundant proteins of the CyHV-3 secretome. To investigate the role of ORF134 in
      viral replication in vitro and in virulence in vivo, a deleted strain and a
      derived revertant strain were produced using BAC cloning technologies. The
      recombinant ORF134 deleted strain replicated in vitro comparably to the parental
      and the revertant strains. Infection of fish by immersion in water containing the
      virus induced comparable CyHV-3 disease for the three virus genotypes tested
      (wild type, deleted and revertant). Quantification of viral DNA by real time
      TaqMan PCR (in the gills and the kidney) and analysis of carp cytokine expression
      (in the spleen) by RT-qPCR at different times post-infection did not revealed any
      significant difference between the groups of fish infected with the three virus
      genotypes. Similarly, histological examination of the gills and the kidney of
      infected fish revealed no significant differences between fish infected with
      ORF134 deleted virus versus fish infected with the control parental or revertant
      strains. All together, the results of the present study demonstrate that the IL
      10 homologue encoded by CyHV-3 is essential neither for viral replication in
      vitro nor for virulence in common carp. 

PMID- 23865543
TI  - Antineutrophil cytoplasmic antibody-associated necrotizing glomerulonephritis:
      Not always pauci-immune.

PMID- 23865544
TI  - Perforation of the left innominate vein during cannulation for haemodialysis.

PMID- 23865545
TI  - Reversal of dabigatran with haemodialysis in a patient requiring decompression
      for cord compression from an epidural abscess.

PMID- 23865546
TI  - QM/MM structural and spectroscopic analysis of the di-iron(II) and di-iron(III)
      ferroxidase site in M ferritin.
AB  - Ferritins are cage-like proteins composed of 24 subunits that take up iron(II)
      and store it as an iron(III) oxide mineral core. A critical step is the
      ferroxidase reaction, in which oxygen reacts with a di-iron(II) site, proceeding
      through a peroxo intermediate, to form MU-oxo/hydroxo-bridged di-iron(III)
      products. The recent crystal structures of copper(II)- and iron(III)-bound frog M
      ferritin at 2.8 A resolution [Bertini; et al. J. Am. Chem. Soc. 2012, 134, 6169
      6176] provided an opportunity to theoretically investigate the detailed
      structures of the reactant state and products. In this study, the quantum
      mechanical/molecular mechanical ONIOM method is used to structurally optimize a
      series of single-subunit models with various hydration, protonation, and
      coordination states of the ferroxidase site. Calculated exchange coupling
      constants (J), Mossbauer parameters, and time-dependent density functional
      theoretical (TD-DFT) circular dichroism spectra with electronic embedding are
      compared with the available experimental data. The di-iron(II) model with the
      most experimentally consistent structural and spectroscopic parameters has 5
      coordinate iron centers with Glu23, Glu58, His61, and two waters completing one
      coordination sphere, and His54, Glu58, Glu103, and Asp140 completing the other.
      In contrast to a previously proposed structure, Gln137 is not directly
      coordinated, but it is involved in hydrogen bonding with several iron ligands.
      For the di-iron(III) products, we find that a MU-oxo-bridged and two doubly
      bridged (MU-hydroxo and MU-oxo/hydroxo) species are likely coproduced. Although
      four quadrupole doublets were observed experimentally, we find that two doublets
      may arise from a single asymmetrically coordinated ferroxidase site. These
      proposed key structures will help to explore the pathway connecting the di-Fe(II)
      state to the peroxo intermediate and the branching mechanisms leading to the
      multiple products.

PMID- 23865547
TI  - Effects of double filtration plasmapheresis on nocturnal respiratory function in
      myasthenic patients.
AB  - Assessment of respiratory function using combined oximetry-cutaneous capnography
      has never been evaluated in patients with myasthenia gravis (MG). We investigated
      the effects of double filtration plasmapheresis (DFPP) on respiratory status in
      18 MG patients. Results of combined oximetry and transcutaneous capnography, MG
      scores, and acetylcholine receptor antibody titers before and after DFPP
      treatment were compared. The respiratory monitoring was performed at three time
      periods (morning, afternoon, and sleep). Mean MG score was markedly lower after
      DFPP treatment (5.7) than before treatment (7.9). Before DFPP, the minimum pulse
      oximetric saturation (SpO2 ) level obtained during the night session was
      significantly lower (P = 0.0513 and P = 0.0199) than the levels obtained during
      the two daytime sessions. A similar phenomenon was noted for maximum
      transcutaneous carbon dioxide tension (PtcCO2 ). After DFPP treatment, the
      maximum and mean PtcCO2 levels were significantly higher (P = 0.0056) in the
      morning than in the afternoon. Of all the respiratory function parameters
      measured, only minimum SpO2 levels obtained during morning sessions before DFP
      treatment differed significantly from those obtained after DFPP treatment (P =
      0.0322). Overall, however, minimum SpO2 levels as well as mean and maximum PtcCO2
      levels improved significantly during sleep after DFPP. In conclusion, we found
      that respiratory function abnormalities were common in myasthenic patients
      without clinical respiratory symptoms. DFPP treatment resulted in minimal
      improvement of respiratory parameters.

PMID- 23865548
TI  - Compact representations of extended causal models.
AB  - Judea Pearl (2000) was the first to propose a definition of actual causation
      using causal models. A number of authors have suggested that an adequate account
      of actual causation must appeal not only to causal structure but also to
      considerations of normality. In Halpern and Hitchcock (2011), we offer a
      definition of actual causation using extended causal models, which include
      information about both causal structure and normality. Extended causal models are
      potentially very complex. In this study, we show how it is possible to achieve a
      compact representation of extended causal models. 

PMID- 23865549
TI  - Fracture strength of monolithic all-ceramic crowns made of high translucent
      yttrium oxide-stabilized zirconium dioxide compared to porcelain-veneered crowns
      and lithium disilicate crowns.
AB  - OBJECTIVE: The aim of the study was to provide data on the fracture strength of
      monolithic high translucent Y-TZP crowns and porcelain-veneered high translucent
      Y-TZP crown cores and to compare that data with the fracture strength of
      porcelain-veneered Y-TZP crown cores and monolithic lithium disilicate glass
      ceramic crowns. MATERIALS AND METHODS: Sixty standardized crowns divided into six
      groups (n = 10) were fabricated: monolithic high translucent Y-TZP crowns, brand
      A, monolithic high translucent Y-TZP crowns, brand B, veneered high translucent Y
      TZP crown cores, brand A, veneered high translucent Y-TZP crown cores, brand B,
      heat-pressed monolithic lithium disilicate crowns and veneered Y-TZP crown cores.
      All crowns were thermocycled, cemented onto dies, cyclically pre-loaded and
      finally loaded to fracture. RESULTS: The monolithic Y-TZP groups showed
      significantly higher fracture strength (2795 N and 3038 N) compared to all other
      groups. The fracture strength in the veneered Y-TZP group (2229 N) was
      significantly higher than the monolithic lithium disilicate group (1856 N) and
      the veneered high translucent Y-TZP groups (1480 N and 1808 N). CONCLUSIONS: The
      fracture strength of monolithic high translucent Y-TZP crowns is considerably
      higher than that of porcelain-veneered Y-TZP crown cores, porcelain-veneered high
      translucent Y-TZP crown cores and monolithic lithium disilicate crowns. The
      fracture strength of a crown made of monolithic high translucent Y-TZP is, with a
      large safety margin, sufficient for clinical use for the majority of patients.
      Porcelain-veneered Y-TZP crown cores show higher fracture resistance than
      monolithic lithium disilicate crowns.

PMID- 23865550
TI  - Infant dental enucleation: A literature review on a traditional remedial practice
      in East Africa.
AB  - OBJECTIVE: To summarize and review the literature on infant dental enucleation, a
      traditional remedial procedure prevalent mainly in East Africa. MATERIALS AND
      METHODS: Literature searches were made electronically using general and
      specialized search engines. The main search was performed through a systematic
      strategy in PubMed, comprising tabulated keywords, search codes, and translated
      and transliterated terms. Criteria for the selection of studies were designed to
      provide a general understanding of the procedure. The findings were synthesized
      into two sections: a summary of the population prevalence studies, and a thematic
      literature review. RESULTS: An overview of the known prevalence and clinical
      specifications was established. Insight was gained into the purpose of the
      procedure and the factors influencing its performance. Diverging suggestions were
      seen with regard to the rationale for use of infant dental enucleation between
      different populations. Moreover, reports of complications and consequences
      involving the general health and the dentoalveolar structures of patients were
      examined. CONCLUSIONS: Prevalence, clinical features and risks of infant dental
      enucleation point to a need for greater awareness of the procedure. Further,
      there is a need for specific guidelines regarding management of suspected cases
      within dental and healthcare communities.

PMID- 23865552
TI  - CHARMM-GUI micelle builder for pure/mixed micelle and protein/micelle complex
      systems.
AB  - Micelle Builder in CHARMM-GUI, http://www.charmm-gui.org/input/micelle , is a web
      based graphical user interface to build pure/mixed micelle and protein/micelle
      complex systems for molecular dynamics (MD) simulation. The robustness of Micelle
      Builder is tested by simulating four detergent-only homogeneous micelles of DHPC
      (dihexanoylphosphatidylcholine), DPC (dodecylphosphocholine), TPC
      (tetradecylphosphocholine), and SDS (sodium dodecyl sulfate) and comparing the
      calculated micelle properties with experiments and previous simulations. As a
      representative protein/micelle model, Pf1 coat protein is modeled and simulated
      in DHPC micelles with three different numbers of DHPC molecules. While the number
      of DHPC molecules in direct contact with Pf1 protein converges during the
      simulation, distinct behavior and geometry of micelles lead to different protein
      conformations in comparison to that in bilayers. It is our hope that CHARMM-GUI
      Micelle Builder can be used for simulation studies of various protein/micelle
      systems to better understand the protein structure and dynamics in micelles as
      well as distribution of detergents and their dynamics around proteins. 

PMID- 23865553
TI  - MicroRNA-21: a therapeutic target for reversing drug resistance in cancer.
AB  - INTRODUCTION: Drug resistance is a major clinical obstacle to the successful
      treatment of human cancer. The microRNAs-21 (miR-21), an oncomiR, may play an
      important role in the progress of drug resistance. AREAS COVERED: This review
      covers all related literature on miR-21 in drug resistance of human cancers and
      analyzes the expression, biological functions and targets of it. This study also
      envisages future developments toward its clinical and therapeutic applications in
      cancer treatment. EXPERT OPINION: The miR-21 may promote the drug resistance of
      various cancers. Inhibitors of miR-21 may function as effective approaches for
      reversing drug resistance in cancer cells. There is a tough way from discovering
      the function of miR-21 to clinical use. Further understanding of miR-21-mediated
      signaling pathways will help to promote the therapeutic-clinical use of miR-21 in
      cancer.

PMID- 23865551
TI  - In vivo bone regeneration using tubular perfusion system bioreactor cultured
      nanofibrous scaffolds.
AB  - The use of bioreactors for the in vitro culture of constructs for bone tissue
      engineering has become prevalent as these systems may improve the growth and
      differentiation of a cultured cell population. Here we utilize a tubular
      perfusion system (TPS) bioreactor for the in vitro culture of human mesenchymal
      stem cells (hMSCs) and implant the cultured constructs into rat femoral condyle
      defects. Using nanofibrous electrospun poly(lactic-co-glycolic acid)/poly(epsilon
      caprolactone) scaffolds, hMSCs were cultured for 10 days in vitro in the TPS
      bioreactor with cellular and acellular scaffolds cultured statically for 10 days
      as a control. After 3 and 6 weeks of in vivo culture, explants were removed and
      subjected to histomorphometric analysis. Results indicated more rapid bone
      regeneration in defects implanted with bioreactor cultured scaffolds with a new
      bone area of 1.23 +/- 0.35 mm(2) at 21 days compared to 0.99 +/- 0.43 mm(2) and
      0.50 +/- 0.29 mm(2) in defects implanted with statically cultured scaffolds and
      acellular scaffolds, respectively. At the 21 day timepoint, statistical
      differences (p<0.05) were only observed between defects implanted with cell
      containing scaffolds and the acellular control. After 42 days, however, defects
      implanted with TPS cultured scaffolds had the greatest new bone area with 1.72 +/
      0.40 mm(2). Defects implanted with statically cultured and acellular scaffolds
      had a new bone area of 1.26 +/- 0.43 mm(2) and 1.19 +/- 0.33 mm(2), respectively.
      The increase in bone growth observed in defects implanted with TPS cultured
      scaffolds was statistically significant (p<0.05) when compared to both the static
      and acellular groups at this timepoint. This study demonstrates the efficacy of
      the TPS bioreactor to improve bone tissue regeneration and highlights the
      benefits of utilizing perfusion bioreactor systems to culture MSCs for bone
      tissue engineering.

PMID- 23865554
TI  - Long-term results of a three arms prospective cohort study on implants in
      periodontally compromised patients: 10-year data around sandblasted and acid
      etched (SLA) surface.
AB  - OBJECTIVES: The aim of this study was to compare the long-term outcomes of
      sandblasted and acid-etched (SLA) implants in patients previously treated for
      periodontitis and in periodontally healthy patients (PHP). MATERIAL AND METHODS:
      One hundred and forty-nine partially edentulous patients were consecutively
      enrolled in private specialist practice and divided into three groups according
      to their periodontal condition: PHP, moderately periodontally compromised
      patients (PCP) and severely PCP. Implants were placed to support fixed
      prostheses, after successful completion of initial periodontal therapy. At the
      end of active periodontal treatment (APT), patients were asked to follow an
      individualized supportive periodontal therapy (SPT) program. Diagnosis and
      treatment of peri-implant biological complications were performed according to
      cumulative interceptive supportive therapy (CIST). At 10 years, clinical and
      radiographic measures were recorded by two calibrated operators, blind to the
      initial patient classification, on 123 patients, as 26 were lost to follow up.
      The number of sites treated according to therapy modalities C and D (antibiotics
      and/or surgery) during the 10 years was registered. RESULTS: Six implants were
      removed for biological complications. The implant survival rate was 100% for PHP,
      96.9% for moderate PCP and 97.1% for severe PCP. Antibiotic and/or surgical
      therapy was performed in 18.8% of cases in PHP, in 52.2% of cases in moderate PCP
      and in 66.7% cases in severe PCP, with a statistically significant differences
      between PHP and both PCP groups. At 10 years, the percentage of implants, with at
      least one site that presented a PD >= 6 mm, was, respectively, 0% for PHP, 9.4%
      for moderate PCP and 10.8% for severe PCP, with a statistically significant
      difference between PHP and both PCP groups. CONCLUSIONS: This study shows that
      SLA implants, placed under a strict periodontal control, offer predictable long
      term results. Nevertheless, patients with a history of periodontitis, who did not
      fully adhere to the SPT, presented a statistically significant higher number of
      sites that required additional surgical and/or antibiotic treatment. Therefore,
      patients should be informed, from the beginning, of the value of the SPT in
      enhancing long-term outcomes of implant therapy, particularly those affected by
      periodontitis.

PMID- 23865555
TI  - A predicted functional gene network for the plant pathogen Phytophthora infestans
      as a framework for genomic biology.
AB  - BACKGROUND: Associations between proteins are essential to understand cell
      biology. While this complex interplay between proteins has been studied in model
      organisms, it has not yet been described for the oomycete late blight pathogen
      Phytophthora infestans. RESULTS: We present an integrative probabilistic
      functional gene network that provides associations for 37 percent of the
      predicted P. infestans proteome. Our method unifies available genomic,
      transcriptomic and comparative genomic data into a single comprehensive network
      using a Bayesian approach. Enrichment of proteins residing in the same or related
      subcellular localization validates the biological coherence of our predictions.
      The network serves as a framework to query existing genomic data using network
      based methods, which thus far was not possible in Phytophthora. We used the
      network to study the set of interacting proteins that are encoded by genes co
      expressed during sporulation. This identified potential novel roles for proteins
      in spore formation through their links to proteins known to be involved in this
      process such as the phosphatase Cdc14. CONCLUSIONS: The functional association
      network represents a novel genome-wide data source for P. infestans that also
      acts as a framework to interrogate other system-wide data. In both capacities it
      will improve our understanding of the complex biology of P. infestans and related
      oomycete pathogens.

PMID- 23865557
TI  - Ablation effect indicated by impedance fall is correlated with contact force
      level during ablation for atrial fibrillation.
AB  - INTRODUCTION: Previous studies have validated the use of impedance fall as a
      measure of the effects of ablation. We investigated whether catheter-to-tissue
      contact force correlated with impedance fall during atrial fibrillation ablation.
      METHODS AND RESULTS: A total of 394 ablation points from 35 patients who
      underwent atrial fibrillation ablation were selected and analyzed in terms of the
      presence of stable catheter contact in non-ablated areas in the left atrium. A
      fixed power output (30 W) was applied for 60 seconds. Contact force, impedance
      fall, and force-direction angle were retrieved and exported for off-line
      analysis. Qualified points were divided into 5 groups according to the level of
      contact force (1-5 g, 6-10 g, 11-15 g, 16-20 g, and >20 g). An acute impedance
      fall was observed in the first 10 seconds followed by a plateau in group I and by
      a further fall in the other groups. Group V showed a rise in impedance during the
      last 20 seconds of ablation. Levels of impedance fall at each time point were
      significantly different among all the groups (P<0.001) except between groups III
      and IV. There was a significant correlation between contact force and maximum
      impedance fall (rho = 0.54, P<0.01). Lesions with a force-direction angle of 0-30
      degrees  had significantly lower contact force and maximum impedance fall than
      those with angles of 30-60 degrees  and 60-135 degrees  (P<0.01). CONCLUSIONS:
      Under stable catheter conditions, contact force correlates with impedance fall
      during 60 seconds of ablation. Contact force exceeding 5 g produces greater
      impedance fall, which probably indicates adequate lesion formation. A contact
      force greater than 20 g may lead to late tissue overheating.

PMID- 23865556
TI  - Levels of heroin and its metabolites in blood and brain extracellular fluid after
      i.v. heroin administration to freely moving rats.
AB  - BACKGROUND AND PURPOSE: Heroin, with low affinity for MU-opioid receptors, has
      been considered to act as a prodrug. In order to study the pharmacokinetics of
      heroin and its active metabolites after i.v. administration, we gave a bolus
      injection of heroin to rats and measured the concentration of heroin and its
      metabolites in blood and brain extracellular fluid (ECF). EXPERIMENTAL APPROACH:
      After an i.v. bolus injection of heroin to freely moving Sprague-Dawley rats, the
      concentrations of heroin and metabolites in blood samples from the vena jugularis
      and in microdialysis samples from striatal brain ECF were measured by
      ultraperformance LC-MS/MS. KEY RESULTS: Heroin levels decreased very fast, both
      in blood and brain ECF, and could not be detected after 18 and 10 min
      respectively. 6-Monoacetylmorphine (6-MAM) increased very rapidly, reaching its
      maximal concentrations after 2.0 and 4.3 min, respectively, and falling
      thereafter. Morphine increased very slowly, reaching its maximal levels, which
      were six times lower than the highest 6-MAM concentrations, after 12.6 and 21.3
      min, with a very slow decline during the rest of the experiment and only
      surpassing 6-MAM levels at least 30 min after injection. CONCLUSIONS AND
      IMPLICATIONS: After an i.v. heroin injection, 6-MAM was the predominant opioid
      present shortly after injection and during the first 30 min, not only in the
      blood but also in rat brain ECF. 6-MAM might therefore mediate most of the
      effects observed shortly after heroin intake, and this finding questions the
      general assumption that morphine is the main and most important metabolite of
      heroin.

PMID- 23865558
TI  - Novel polymerase gamma (POLG1) gene mutation in the linker domain associated with
      parkinsonism.
AB  - BACKGROUND: Mutations in the POLG1 gene have variable phenotypic presentations
      and a high degree of clinical suspicion is necessary for their recognition.
      Parkinsonism and ataxia are the most common movement disorders associated with
      POLG1 mutations but no phenotype-genotype correlation has been established. CASE
      PRESENTATION: We identified a male patient with progressive external
      ophthalmoplegia who also developed a progressive bradykinesia, rigidity and
      camptocormia in the third decade. Parkinsonism was partially responsive to
      dopaminegic replacement. His father and brother had reportedly similar clinical
      problems. Genetic analysis identified a novel mutation p.K512M in the POLG1 gene.
      CONCLUSION: This report further expands the spectrum of POLG1-associated
      neurologic problems with the report of a novel mutation in the linker region of
      the gene, which are rarely associated with parkinsonism.

PMID- 23865559
TI  - Mechanisms of acceleration and retardation of water dynamics by ions.
AB  - There are fundamental and not yet fully resolved questions concerning the impact
      of solutes, ions in particular, on the structure and dynamics of water, which can
      be formulated as follows: Are the effects of ions local or long-ranged? Is the
      action of cations and anions on water cooperative or not? Here, we investigate
      how the reorientation and hydrogen-bond dynamics of water are affected by ions in
      dilute and concentrated aqueous salt solutions. By combining simulations and
      analytic modeling, we first show that ions have a short-ranged influence on the
      reorientation of individual water molecules and that depending on their
      interaction strength with water, they may accelerate or slow down water dynamics.
      A simple additive picture combining the effects of the cations and anions is
      found to provide a good description in dilute solutions. In concentrated
      solutions, we show that the average water reorientation time ceases to scale
      linearly with salt concentration due to overlapping hydration shells and
      structural rearrangements which reduce the translational displacements induced by
      hydrogen-bond switches and increase the solution viscosity. This effect is not
      ion-specific and explains why all concentrated salt solutions slow down water
      dynamics. Our picture, which is demonstrated to be robust vis-a-vis a change in
      the force-field, reconciles the seemingly contradictory experimental results
      obtained by ultrafast infrared and NMR spectroscopies, and suggests that there
      are no long-ranged cooperative ion effects on the dynamics of individual water
      molecules in dilute solutions. 

PMID- 23865560
TI  - Forensic identification of CITES protected slimming cactus (Hoodia) using DNA
      barcoding.
AB  - Slimming cactus (Hoodia), found only in southwestern Africa, is a well-known
      herbal product for losing weight. Consequently, Hoodia extracts are sought-after
      worldwide despite a CITES Appendix II status. The failure to eradicate illegal
      trade is due to problems with detecting and identifying Hoodia using
      morphological and chemical characters. Our aim was to evaluate the potential of
      molecular identification of Hoodia based on DNA barcoding. Screening of nrITS1
      and psbA-trnH DNA sequences from 26 accessions of Ceropegieae resulted in
      successful identification, while conventional chemical profiling using DLI-MS led
      to inaccurate detection and identification of Hoodia. The presence of Hoodia in
      herbal products was also successfully established using DNA sequences. A
      validation procedure of our DNA barcoding protocol demonstrated its robustness to
      changes in PCR conditions. We conclude that DNA barcoding is an effective tool
      for Hoodia detection and identification which can contribute to preventing
      illegal trade.

PMID- 23865561
TI  - Nonlinear active materials: an illustration of controllable phase matchability.
AB  - For a crystal to exhibit nonlinear optical (NLO) activity such as second-harmonic
      generation (SHG), it must belong to a noncentrosymmetric (NCS) space group.
      Moreover, for these nonlinear optical (NLO) materials to be suitable for
      practical uses, the synthesized crystals should be phase-matchable (PM). Previous
      synthetic research into SHG-active crystals has centered on (i) how to create NCS
      compounds and/or (ii) how to obtain NCS compounds with high SHG efficiencies.
      With these tactics, one can synthesize a material with a high SHG efficiency, but
      the material could be unusable if the material was nonphase-matchable (non-PM).
      To probe the origin of phase matchability of NCS structures, we present two new
      chemically similar hybrid compounds within one composition space: (I)
      [Hdpa]2NbOF5.2H2O and (II) HdpaNbOF4 (dpa = 2,2'-dipyridylamine). Both compounds
      are NCS and chemically similar, but (I) is non-PM while (II) is PM. Our results
      indicate--consistent with organic crystallography--the arrangement of the organic
      molecule within hybrid materials dictates whether the material is PM or non-PM.

PMID- 23865562
TI  - Fish consumption patterns, knowledge and potential exposure to mercury by race.
AB  - OBJECTIVE: Compared fish consumption patterns, fish advisory/benefit awareness
      and risk factors of consuming high-mercury (Hg) fish between Chinese and non
      Chinese adults. METHODS: 301 Chinese and 120 non-Chinese participated in this
      cross-sectional study. Participants self-reported demographics, fish consumption
      behavior, and awareness of warnings/benefits of fish consumption. RESULTS: non
      Chinese (62.5%) ate more high-Hg fish than Chinese (35.9%) although more Chinese
      ate fish in the last year. Over 90% of both groups knew general benefits of
      consuming fish; fewer knew specific benefits. Chinese were less aware of fish
      warnings (49.8%) than non-Chinese (86.7%); knowledge did not appear to affect
      their fish consumption. CONCLUSIONS: There were significant differences in fish
      consumption patterns and fish benefit/warning knowledge between the two groups. A
      higher proportion of non-Chinese reported consumption of high-Hg fish. Fish
      knowledge did not affect fish consumption behavior for either group. Public
      education efforts regarding fish consumption should emphasize details such as
      species and amounts.

PMID- 23865563
TI  - Polyetherimide/bucky gels nanocomposites with superior conductivity and thermal
      stability.
AB  - Polyetherimide (PEI) nanocomposites comprising bucky gels of industrial-grade
      multiwalled carbon nanotubes (MWCNTs) and ionic liquid (IL, 1-butyl-3-methyl
      imidazolium hexafluorophosphate ([BMIM][PF6])) were prepared. The processing
      framework for this nanocomposite is simple, reproducible, and easily scalable.
      The strong interaction between IL and MWCNTs caused the latter to uniformly
      disperse in the PEI matrix while IL flowed into the gaps between the nanotubes'
      walls. The nanocomposite exhibited an enhanced conductivity of 2.01 * 10(4)
      Omega.cm volume resistivity at room temperature; the value decreased dramatically
      by 12 orders of magnitude, compared to pristine PEI. The IL free ions and MWCNTs
      networks provided excellent channels for electron transfer. PEI/bucky gels
      nanocomposites also showed improved thermal stability and high tensile strength.
      Other than having antiwear properties, this material can have numerous
      applications in the aerospace and electronics industries. Moreover, our work
      presents a "green" method toward modified nanocomposites industrial production as
      IL is environmentally safe and is easily recyclable. 

PMID- 23865564
TI  - Development and validity of a questionnaire to test the knowledge of primary care
      personnel regarding nutrition in obese adolescents.
AB  - BACKGROUND: In light of its epidemic proportions in developed and developing
      countries, obesity is considered a serious public health issue. In order to
      increase knowledge concerning the ability of health care professionals in caring
      for obese adolescents and adopt more efficient preventive and control measures, a
      questionnaire was developed and validated to assess non-dietitian health
      professionals regarding their Knowledge of Nutrition in Obese Adolescents (KNOA).
      METHODS: The development and evaluation of a questionnaire to assess the
      knowledge of primary care practitioners with respect to nutrition in obese
      adolescents was carried out in five phases, as follows: 1) definition of study
      dimensions 2) development of 42 questions and preliminary evaluation of the
      questionnaire by a panel of experts; 3) characterization and selection of primary
      care practitioners (35 dietitians and 265 non-dietitians) and measurement of
      questionnaire criteria by contrasting the responses of dietitians and non
      dietitians; 4) reliability assessment by question exclusion based on item
      difficulty (too easy and too difficult for non-dietitian practitioners), item
      discrimination, internal consistency and reproducibility index determination; and
      5) scoring the completed questionnaires. RESULTS: Dietitians obtained higher
      scores than non-dietitians (Mann-Whitney U test, P < 0.05), confirming the
      validity of the questionnaire criteria. Items were discriminated by correlating
      the score for each item with the total score, using a minimum of 0.2 as a
      correlation coefficient cutoff value. Item difficulty was controlled by excluding
      questions answered correctly by more than 90% of the non-dietitian subjects (too
      easy) or by less than 10% of them (too difficult). The final questionnaire
      contained 26 of the original 42 questions, increasing Cronbach's alpha value from
      0.788 to 0.807. Test-retest agreement between respondents was classified as good
      to very good (Kappa test, >0.60). CONCLUSION: The KNOA questionnaire developed
      for primary care practitioners is a valid, consistent and suitable instrument
      that can be applied over time, making it a promising tool for developing and
      guiding public health policies.

PMID- 23865565
TI  - High-sensitivity naphthalene-based two-photon fluorescent probe suitable for
      direct bioimaging of H2S in living cells.
AB  - H2S is the third endogenously generated gaseous signaling compound and has also
      been known to involve a variety of physiological processes. To better understand
      its physiological and pathological functions, efficient methods for monitoring of
      H2S in living systems are desired. Although quite a few one photon fluorescence
      probes have been reported for H2S, two-photon (TP) probes are more favorable for
      intracellular imaging. In this work, by employing a donor-pi-acceptor-structured
      naphthalene derivative as the two-photon fluorophore and an azide group as the
      recognition unit, we reported a new two-photon bioimaging probe 6
      (benzo[d]thiazol-2'-yl)-2-azidonaphthalene (NHS1) for H2S with improved
      sensitivity. The probe shows very low background fluorescence in the absence of
      H2S. In the presence of H2S, however, a significant enhancement for both one
      photon and TP excited fluorescence were observed, resulting in a high sensitivity
      to H2S in aqueous solutions with a detection limit of 20 nM observed, much lower
      than the previously reported TP probe. The probe also exhibits a wide linear
      response concentration range (0-5 MUM) to H2S with high selectivity. All these
      features are favorable for direct monitoring of H2S in complex biological
      samples. It was then applied for direct TP imaging of H2S in living cells with
      satisfactory sensitivity, demonstrating its value of practical application in
      biological systems. 

PMID- 23865567
TI  - Supervised evolution: research concerning the number of evolutions that occur
      under certain constraints.
AB  - It is known that evolution may lead to a new species while adaptation may lead to
      a new variety. In this manuscript, we present an analysis of the number of
      evolutions (defined by improvement of the score associated with an objective
      function of a genetic algorithm) in an experiment supervised by a genetic
      algorithm, experiment conducted on octan-1-ol/H20 partition coefficient of
      polychlorinated biphenyls. The numbers of evolutions resulted from 9 implemented
      evolution strategies were investigated. Evolutions arisen from the first 20 000
      generations coming from 46 independent runs were recorded. A distribution
      analysis has been conducted for each evolution strategy. Without exception, the
      Weibull distribution fits well with the number of evolutions at a significance
      level of 5% for any evolution strategy. Furthermore, the Weibull distribution
      could not be rejected when different merged samples were investigated. 

PMID- 23865566
TI  - EndoS2 is a unique and conserved enzyme of serotype M49 group A Streptococcus
      that hydrolyses N-linked glycans on IgG and alpha1-acid glycoprotein.
AB  - Many bacteria have evolved ways to interact with glycosylation functions of the
      immune system of their hosts. Streptococcus pyogenes [GAS (group A
      Streptococcus)] secretes the enzyme EndoS that cleaves glycans on human IgG and
      impairs the effector functions of the antibody. The ndoS gene, encoding EndoS,
      has, until now, been thought to be conserved throughout the serotypes. However,
      in the present study, we identify EndoS2, an endoglycosidase in serotype M49 GAS
      strains. We characterized EndoS2 and the corresponding ndoS2 gene using
      sequencing, bioinformatics, phylogenetic analysis, recombinant expression and LC
      MS analysis of glycosidic activity. This revealed that EndoS2 is present
      exclusively, and highly conserved, in serotype M49 of GAS and is only 37%
      identical with EndoS. EndoS2 showed endo-beta-N-acetylglucosaminidase activity on
      all N-linked glycans of IgG and on biantennary and sialylated glycans of AGP
      (alpha1-acid glycoprotein). The enzyme was found to act only on native IgG and
      AGP and to be specific for free biantennary glycans with or without terminal
      sialylation. GAS M49 expression of EndoS2 was monitored in relation to
      carbohydrates present in the culture medium and was linked to the presence of
      sucrose. We conclude that EndoS2 is a unique endoglycosidase in serotype M49 and
      differs from EndoS of other GAS strains by targeting both IgG and AGP. EndoS2
      expands the repertoire of GAS effectors that modify key glycosylated molecules of
      host defence. 

PMID- 23865568
TI  - Vaccination with recombinant NetB toxin partially protects broiler chickens from
      necrotic enteritis.
AB  - NetB toxin from Clostridium perfringens is a major virulence factor in necrotic
      enteritis in poultry. In this study the efficacy of NetB as a vaccine antigen to
      protect chickens from necrotic enteritis was examined. Broiler chickens were
      immunized subcutaneously with purified recombinant NetB (rNetB), formalin treated
      bacterin and cell free toxoid with or without rNetB supplementation. Intestinal
      lesion scores and NetB antibody levels were measured to determine protection
      after mild oral gavage, moderate in-feed and heavy in-feed challenges with
      virulent C. perfringens isolates. Birds immunized with rNetB were significantly
      protected against necrotic enteritis when challenged with a mild oral dose of
      virulent bacteria, but were not protected when a more robust challenge was used.
      Bacterin and cell free toxoid without rNetB supplementation did not protect birds
      from moderate and severe in-feed challenge. Only birds immunized with bacterin
      and cell free toxoid supplemented with rNetB showed significant protection
      against moderate and severe in-feed challenge, with the later giving the greatest
      protection. Higher NetB antibody titres were observed in birds immunized with
      rNetB compared to those vaccinated with bacterin or toxoid, suggesting that the
      in vitro levels of NetB produced by virulent C. perfringens isolates are too low
      to induce the development of a strong immune response. These results suggest that
      vaccination with NetB alone may not be sufficient to protect birds from necrotic
      enteritis in the field, but that in combination with other cellular or cell-free
      antigens it can significantly protect chickens from disease. 

PMID- 23865570
TI  - Photocatalytic hydrogen generation system using a nickel-thiolate hexameric
      cluster.
AB  - We report the use of a nickel-thiolate hexameric cluster, Ni6(SC2H4Ph)12, for
      photocatalytic hydrogen production from water. The nickel cluster was synthesized
      ex-situ and characterized by various techniques. Single crystal X-ray analysis,
      (1)H NMR, 2D COSY, ESI-MS, UV-visible spectroscopy, and TGA provided insight into
      the structure and confirmed the purity and stability of the cluster. Cyclic
      voltammetry helped confirm hydrogen evolution reaction (HER) activity of this
      catalyst. Photoreactions carried out using an iridium photosensitizer, Ir(F
      mppy)2(dtbbpy)[PF6], and TEA as the sacrificial reductant revealed the high
      activity of the Ni6 cluster as a water reducing catalyst. High TONs (3750) and
      TOFs (970 h(-1)) were obtained at optimum catalyst concentration (0.025 mM), with
      low concentrations of catalyst yielding up to 30,000 turnovers. Quenching
      studies, along with the evidence obtained from the electrochemical analysis,
      showed that this water reduction system proceeds through a reductive quenching
      mechanism. Mercury poisoning studies confirmed that no active, metallic colloids
      were formed during the photocatalytic reaction.

PMID- 23865569
TI  - Cold induces reactive oxygen species production and activation of the NF-kappa B
      response in endothelial cells and inflammation in vivo.
AB  - BACKGROUND: Organs intended for transplantation are generally stored in the cold
      for better preservation of their function. However, following transplantation and
      reperfusion, the microvasculature of transplanted organs often proves to be
      activated. Extensive leukocyte adhesion and microthrombus formation contribute to
      failure of the transplanted organ. OBJECTIVES: In this study we analyzed cold
      induced changes to the activation status of cultured endothelial cells, possibly
      contributing to organ failure. METHODS: We exposed human umbilical vein
      endothelial cells (HUVECs) to temperatures below 37  degrees C (mostly to 8 
      degrees C) for 30 min and upon rewarming to 37  degrees C kept incubating them
      for up to 24 h. We also in vivo locally exposed mice to cold. RESULTS: The
      exposure to low temperatures induced, in HUVECs, expression of the prothrombotic
      factors plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and of
      the inflammatory adhesion molecules, E-selectin, intracellular adhesion molecule
      1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, upon
      rewarming for 30 min, we detected activation of the inflammatory NF-kappaB
      pathway, as measured by transient NF-kappaB translocation to the nucleus and
      IkappaBalpha degradation. Using butylated hydroxytoluene (BHT), a scavenger of
      reactive oxygen species (ROS), we further demonstrated that cold-induced NF
      kappaB activation depends on ROS production. Local exposure to cold also, in
      vivo, induced ROS production and ICAM-1 expression and resulted in leukocyte
      infiltration. CONCLUSIONS: Our results point to a causative link between ROS
      production and NF-kappaB activation, suppression of which had been shown to be
      beneficial during hypothermic storage and subsequent rewarming of organs for
      transplantation.

PMID- 23865571
TI  - Over-expression of BACH2 is related to ongoing somatic hypermutation of the
      immunoglobulin heavy chain gene variable region of de novo diffuse large B-cell
      lymphoma.
AB  - The basic region-leucine zipper (bZip) factor BTB, CNC homology 2 (BACH2) is
      known to have important roles in class switch recombination and somatic
      hypermutation (SHM) of the immunoglobulin (Ig) gene. In this study, we
      investigated the relationship between the expression of BACH2 and the status of
      SHM of the Ig heavy chain gene variable region (IgHV) for SHM in diffuse large B
      cell lymphoma (DLBCL). We examined 20 cases of DLBCL, 13 of which were germinal
      center B-cell (GCB) DLBCL and 7 were non-GCB DLBCL. Seven cases were negative, 6
      were positive (cytoplasmic expression) and 7 were strongly positive (both nuclear
      and cytoplasmic expression) for BACH2. Confirmed mutation (CM) was identified in
      8 cases and the CM index (number of confirmed mutations per 10 subclones) was
      distributed from 0 to 5. A CM index of 7 strongly positive (over-expression)
      cases with BACH2 were distributed from 0 to 5, and that of 7 negative and 6
      positive cases were distributed from 0 to 1. Over-expression of BACH2 was
      statistically related to CM index (P = 0.008). In conclusion, over-expression of
      BACH2 is critical for ongoing SHM of IgHV in DLBCL, and our data suggest that
      BACH2 may play an essential role for SHM of the Ig gene in B-cell lymphoma. 

PMID- 23865572
TI  - Fat cells and membranous fat necrosis of aortic valves: a clinicopathological
      study.
AB  - We examined 152 aortic valves (AVs), which included 82 postmortem non
      dysfunctional AVs (nd-AVs) and 70 surgically removed dysfunctional AVs showing
      aortic stenosis (AS), aortic regurgitation (AR), or combined AS and AR (AS-R).
      Fat cells, membranous fat necrosis (MFN), and fat-MFN-related lesions composed of
      fat cells and/or MFN were found in 127 (83.6%), 110 (72.4%), and 140 (92.1%) of
      152 AVs, respectively, and all were associated with older age (P = 0.010, P =
      0.022, and P = 0.003, respectively). MFN was associated with fibrous thickening
      and calcification (both, P = 0.001). Nd-AV fat cells and fat-MFN-related lesions
      were not correlated with body mass index. Compared with age- and sex-matched
      control cases, MFN in AS and AS-R cases was more frequent (P = 0.030 and P =
      0.045, respectively), but MFN in AR cases showed no significant differences. Fat
      MFN-related lesions, possibly representing true preceding fat cells, showed no
      differences in AVs with and without dysfunction or in dysfunctional types. These
      data suggest that AV fat cells are age-related, obesity-independent, and AV
      dysfunction-unrelated common phenomenon. MFN is also age-dependent and could be
      caused by AS and AS-R, which is probably concerned with AV thickening and
      calcification. 

PMID- 23865573
TI  - Desmin-positivity in spindle cells: under-recognized immunophenotype of
      lipoblastoma.
AB  - Lipoblastoma is a distinct benign fatty tumor composed of adipocytes, lipoblasts,
      and primitive mesenchymal cells with a myxoid stroma. Lipoblastoma harbors
      characteristic fusion genes involving the PLAG1, resulting in aberrant expression
      of PLAG1. However, the nature of the primitive mesenchymal cells remains obscure.
      In our routine pathology practice, we noticed desmin-positive spindle mesenchymal
      cells in lipoblastomas, which is a hitherto poorly described phenomenon. Thus, we
      examined the expression of several myogenic markers including desmin in a variety
      of 95 mesenchymal tumors with fatty elements. Fourteen of the 15 lipoblastomas
      examined contained desmin-positive spindle cells, which also showed nuclear
      expression of PLAG1, whereas alpha-smooth muscle actin, muscle specific actin, h
      caldesmon, and myogenin were negative. Some spindle cells in subsets of atypical
      lipomatous tumors/well differentiated liposarcomas (6/20), dedifferentiated
      liposarcomas (11/31) and pleomorphic liposarcomas (2/10) were positive for actins
      and/or desmin, supporting focal myofibroblastic or smooth muscle differentiation.
      The other tumors, including 11 myxoid/round cell liposarcomas, four spindle cell
      lipomas, and four lipofibromatoses, were negative for all of the myogenic markers
      assessed. The almost consistent desmin expression in spindle mesenchymal cells
      suggests a potential diagnostic utility of this marker and myofibroblastic
      phenotype of fractions in lipoblastoma cells. 

PMID- 23865574
TI  - Hepatocyte nuclear factor-1 alpha inactivated hepatocellular adenomas in patient
      with congenital absence of the portal vein: a case report.
AB  - Hepatocellular adenomas (HCAs) have been recognized recently as a heterogeneous
      group, and are subclassified according to genotype as well as morphological
      characteristics. We report a case of a 35-year-old Japanese woman who exhibited
      hepatocyte nuclear factor (HNF)-1alpha-inactivated HCA in the background of the
      congenital absence of the portal vein (CAPV). On a dynamic contrast computed
      tomography (CT) scan, the hypovascular tumor enlarged from 1 cm to 3 cm and
      another tumor emerged in the course of 7 years. Because the possibility of
      hepatocellular carcinoma (HCC) with multiple metastases was not excluded, partial
      hepatectomy was performed. On a cut section, two well-demarcated tumors were
      observed and one tumor had a central fibrous scar. The histological features of
      these tumors were similar to those of focal nodular hyperplasia (FNH) with a
      central scar and HCA; however, these tumors were diagnosed as HNF-1alpha
      inactivated HCA by immunohistochemistry according to the criteria of the current
      World Health Organization (WHO) classification. In non-tumorous liver tissue, an
      abnormal architecture of the vessels and a vague nodular appearance of lobuli
      were observed, which were likely to be those of nodular regenerated hyperplasia
      (NRH). We discuss its pathogenesis and relationship with CAPV.

PMID- 23865575
TI  - Pulmonary sclerosing papillary adenoma.
AB  - Pulmonary papillary adenomas are very rare benign neoplasms, with approximately
      24 cases reported in the English literature. They typically do not contain any
      more than an occasional focal area of sclerosis. Indeed, sclerotic interstitium
      within a sclerosing hemangioma has been reported to be a criterion used to
      distinguish it from pulmonary papillary adenoma. We present a case of pulmonary
      sclerosing papillary adenoma, with extensive sclerotic stroma and scattered areas
      containing typical papillary architecture. 

PMID- 23865576
TI  - Hybrid schwannoma/perineurioma of the spinal nerve: multifocal occurrence, and
      recurrence as an intraneural perineurioma.
AB  - A 63-year-old Japanese man complained of lower back pain and numbness and was
      diagnosed as intradural tumors at the T11/12 and L1 level. The thoracic tumor
      originated from the posterior nerve root, and the lumbar tumor originated from
      the cauda equina. Five months after surgical resection, the patient developed
      recurrent tumor consisting of enlargement of multiple caudal nerves.
      Pathologically, the primary tumors showed a nodular and lobular pattern,
      including spindle cells in a fascicular, whorl and storiform pattern, with
      variable cellularity, nuclear palisading and frequent small onion bulb
      structures. Mild pleomorphism was present, and there were four mitoses per 10
      high power fields. Many cells showed immunoreactivity for S-100 and Sox10. There
      were also claudin-1-positive spindle cells, but no epithelial membrane antigen
      (EMA)-positive cells. The cells in onion bulb structures were positive for
      claudin-1 and glucose transporter 1 (GLUT-1). These findings led to a diagnosis
      of hybrid schwannoma/perineurioma. The features of high cellularity, pleomorphism
      and a Ki-67 index over 10% suggested a low-malignant nature. The recurrent tumor
      also showed high proliferative activity, as reflected by mitotic figures and a Ki
      67 index of 20%. This is the first case of spinal nerve hybrid
      schwannoma/perineurioma with low malignant potential and peculiar intraneural
      perineurioma component. 

PMID- 23865577
TI  - Primary signet-ring cell/histiocytoid carcinoma of the axilla.

PMID- 23865578
TI  - Blastomatoid carcinosarcoma of the lung.

PMID- 23865580
TI  - Hypertriglyceridemic waist and newly-diagnosed diabetes among remote-dwelling
      Indigenous Australians.
AB  - AIMS: Hypertriglyceridemic waist (HTgW) is predictive of cardiovascular disease.
      The HTgW relationship with diabetes is little studied. METHODS: This study
      analysed data from diabetes and cardiovascular risk factor screening programmes
      in remote Indigenous Australian settlements. Elevated waist girth (EW) was
      defined as >=90 cm for men (n = 1134) or >=80 cm for women (n = 1313).
      Hypertriglyceridemia (ETg) was defined as >=1.7 mmol/L. Diabetes was defined as
      fasting plasma glucose >=7.0 mmol/L. Body mass index (BMI) was categorised as
      <22, 22-24.9 and >25.0 kg/m(2). Logistic regression was used to analyse the odds
      of newly-diagnosed diabetes for individuals with either HTgW, ETg or EW, relative
      to individuals with values below cut-offs. RESULTS: The prevalence of HTgW was
      33.2% for men and 34.8% for women. Accounting for age-group and gender, newly
      diagnosed diabetes was associated (odds ratio (OR) (95% confidence interval))
      with HTgW: 9.6 (6.6, 13.8). The relationship remained strong after accounting for
      the covariates BMI and smoking (OR = 4.9 (2.7, 8.8)). In BMI-stratified analyses
      the strongest odds were observed for the lowest category (<22 kg/m(2): OR = 12.9
      (4.0, 41.7)). CONCLUSIONS: HTgW has a high prevalence and is associated with
      newly-diagnosed diabetes in Indigenous people, particularly those with BMI <22
      kg/m(2), whom clinicians might not normally consider for screening.

PMID- 23865579
TI  - Deficiency of the Cog8 subunit in normal and CDG-derived cells impairs the
      assembly of the COG and Golgi SNARE complexes.
AB  - Multiple mutations in different subunits of the tethering complex Conserved
      Oligomeric Golgi (COG) have been identified as a cause for Congenital Disorders
      of Glycosylation (CDG) in humans. Yet, the mechanisms by which COG mutations
      induce the pleiotropic CDG defects have not been fully defined. By detailed
      analysis of Cog8 deficiency in either HeLa cells or CDG-derived fibroblasts, we
      show that Cog8 is required for the assembly of both the COG complex and the Golgi
      Stx5-GS28-Ykt6-GS15 and Stx6-Stx16-Vti1a-VAMP4 SNARE complexes. The assembly of
      these SNARE complexes is also impaired in cells derived from a Cog7-deficient CDG
      patient. Likewise, the integrity of the COG complex is also impaired in Cog1-,
      Cog4- and Cog6-depleted cells. Significantly, deficiency of Cog1, Cog4, Cog6 or
      Cog8 distinctly influences the production of COG subcomplexes and their Golgi
      targeting. These results shed light on the structural organization of the COG
      complex and its subcellular localization, and suggest that its integrity is
      required for both tethering of transport vesicles to the Golgi apparatus and the
      assembly of Golgi SNARE complexes. We propose that these two key functions are
      generally and mechanistically impaired in COG-associated CDG patients, thereby
      exerting severe pleiotropic defects. 

PMID- 23865581
TI  - Effect of simulated tooth temperature on the degree of conversion of self
      adhesive resin cements exposed to different curing conditions.
AB  - OBJECTIVES: This study evaluated the degree of conversion (DC) of two commercial,
      self-adhesive resin cements (SARCs) using Fourier transform infrared analysis
      (FTIR) polymerized at simulated prepared tooth surface temperatures and under
      different curing conditions. MATERIALS AND METHODS: RelyX U100 (U100, 3M ESPE)
      and Maxcem Elite (MX, Kerr Corporation) were mixed at 25 degrees C and applied to
      the surface of a horizontal attenuated total reflectance (ATR) unit, which was
      near room temperature (RT, control) (25 degrees C) or heated to simulate prepared
      tooth surface temperatures (28 degrees C and 32 degrees C) and then attached to
      an infrared spectrometer. The products were polymerized using one of three
      conditions: direct light exposure through a glass slide (DLE), exposure through a
      1.5-mm thick ceramic disc overlay (CO) (A2 shade, IPS e.max, Ivoclar Vivadent),
      or self-curing (SC). FTIR spectra were recorded for 12 minutes (1 spectrum/s, 16
      scans/spectrum, resolution 4 cm(-1)) immediately after application to the ATR.
      The DC was calculated using standard techniques of observing changes in aliphatic
      to-aromatic peak ratios before and 12 minutes after curing, as well as during
      each 1-second interval. DC data (n=7) were analyzed by two-way analysis of
      variance and Tukey's post-hoc test (p=0.05). RESULTS: Both simulated tooth
      temperatures significantly increased DC in all groups of MX and in the CO and SC
      groups of U100 compared with the RT control. For MX, the self-cure groups exposed
      to tooth temperatures showed DC values similar to those of the CO groups. For
      U100, the CO groups showed higher DC values than SC groups regardless of
      temperature. Time-based conversion profiles ranged according to product,
      temperature, and curing mode. CONCLUSIONS: Causing SARCs to polymerize at
      simulated tooth temperatures increases DC of SARCs compared with room-temperature
      curing values, mainly in the SC mode.

PMID- 23865582
TI  - Polymerization shrinkage stress kinetics and related properties of bulk-fill
      resin composites.
AB  - The present study assessed the polymerization shrinkage stress kinetics of five
      low-shrinkage light-cured bulk-fill resin composites: Surefil SDR flow (SF,
      Dentsply), Tetric EvoCeram Bulkfil (TE, Ivoclar Vivadent), Venus Bulk Fill (VB,
      Heraeus Kulzer), x-tra fil (XF, Voco), and experimental bulk fill (FB, 3M ESPE).
      Filtek Z250 (FZ, 3M ESPE) was used as a control. Real-time shrinkage stress of
      investigated composites was measured using a tensometer; maximum shrinkage
      stress, stress rate (Rmax), and time to reach maximum stress rate (tmax) were
      recorded. Flexural strength and modulus were measured using a standard procedure,
      and curing efficiency of 4-mm long specimens was determined using bottom/top
      percentage Knoop microhardness. Data were analyzed using one-way analysis of
      variance and Bonferroni multiple range tests at a significance level of
      alpha=0.05. Results of shrinkage stress, Rmax, and tmax of all bulk-fill
      materials were significantly lower (p<0.05) than those of the control except for
      XF. All tested bulk-fill materials were able to achieve acceptable curing
      efficiency (>=80% bottom/top percentage) at 4-mm depth. In conclusion, this study
      reports a significant reduction in polymerization shrinkage stress while
      maintaining comparable curing efficiency at 4 mm for some bulk-fill composites
      and supports their potential use in posterior clinical situations.

PMID- 23865583
TI  - Microleakage of nanofilled resin-modified glass-ionomer/silorane- or methacrylate
      based composite sandwich Class II restoration: effect of simultaneous bonding.
AB  - OBJECTIVES: Microleakage of composite restorations at the cervical margin placed
      apically to the cementoenamel junction (CEJ) is still a concern. This study
      evaluated the effect of simultaneous bonding application on cervical sealing of
      nano-ionomer/silorane- or methacrylate-based composite open sandwich Class II
      restorations in the modified technique compared with that of conventional
      bonding. METHODS AND MATERIALS: In 60 sound maxillary premolars, two standardized
      Class II cavities were prepared with cervical margins 1 mm below the CEJ. The
      teeth were randomly divided into six groups of 10 teeth each. In the first three
      groups (groups 1-3), Clearfil SE Bond and Clearfil APX (Kuraray) were used for
      restoration in the total bonding technique (group 1), conventional open sandwich
      technique associated with a nano-ionomer (Ketac N100, 3M ESPE) (group 2), and
      modified open sandwich technique with simultaneous bonding application for both
      nano-ionomer and composite (group 3). In the second three groups (groups 4-6),
      Silorane Adhesive and Filtek Silorane composite (3M ESPE) were used in the same
      manner as in the first three groups, respectively. RESULTS: The simultaneous
      bonding application in the modified sandwich restorations (with SE Bond or
      Silorane Adhesive) resulted in a significant reduction of the cervical
      microleakage compared with that of the conventional bonding (p<0.05). However,
      microleakage of the modified technique was similar to that of the total bonding
      (with SE Bond or Silorane Adhesive) (p>0.05), both showing good marginal seal.

PMID- 23865584
TI  - Characterization of depth-related changes in bacterial community compositions and
      functions of a paddy soil profile.
AB  - Depth-related changes in bacterial community structures and functions were
      analyzed in a paddy soil profile using denaturing gradient gel electrophoresis
      (DGGE) and a metabolic profiling technique (BIOLOG ECO plates). Canonical
      correspondence analysis (CCA) was used to analyze the correlations between the
      relative abundance of bacterial groups and soil-available elements. DGGE and
      sequencing analysis revealed 12 classes and one unknown bacterial group. At the
      family level, Comamonadaceae and Moraxellaceae dominated through the soil
      profile, while Acidobacteriaceae and Nitrospiraceae dominated in the deepest
      layer. In addition, Streptococcaceae dominated and was only observed in the
      deeper layers. Metabolic profiles revealed the greatest carbon source utilization
      capacity in the surface layer, and no significant differences between upper and
      deeper soil layers. The carbon sources utilized by microorganisms were different
      among the different layers. CCA indicated that soil-available Mn, Ca, Cu, Al, and
      K concentrations were positively correlated with the relative abundance of
      Comamonadaceae, Moraxellaceae, Streptococcaceae, Microbacteriaceae,
      Nocardioidaceae, and Nitrospiraceae in the profile. The results showed that the
      paddy soil profile harbored diverse bacterial communities and experienced depth
      related changes in community structure and carbon source utilization. The
      bacterial communities and functions might be shaped by the soil edaphic
      characteristics along the soil profile. 

PMID- 23865585
TI  - Response to "letter to the editor" written by Peter Luke Santa Maria, MBBS, PhD.

PMID- 23865586
TI  - Case report of fetal lingual tumor - perinatal care and neonatal surgical
      intervention.
AB  - Fetal tumors are rare and can be difficult to diagnose in utero. In this
      presentation, we report an infantile hemangiopericytoma of the tongue, and also
      review the clinical characteristics, imaging appearances, perinatal differential
      diagnosis, and potential treatments of this tumors. Prenatal diagnosis of lingual
      fetal tumors with two-dimensional (2D) ultrasound presents a challenge to
      sonographers and perinatologists because these lesions are rare, usually develop
      in the third trimester of pregnancy and need a multidisciplinary approach. We
      describe an lingual tumor and moderate polyhydramnios which were prenatally
      detected at 31 weeks of gestation with two- dimensional ultrasound. The
      application of the surface mode of three-dimensional ultrasound improved the
      visualization of this tumor. Fetal Magnetic resonance imaging was performed to
      help in prenatal differential diagnostic. The option of prenatal cytology gained
      by amniocentesis should also be considered. To our knowledge there are no
      prenatal reports of similar cases. However, in our experience every information
      provided during the pregnancy, a correct and early diagnose of fetal condition
      helps to cope with the demands of perinatal management and to explain to the
      parents and neonatologists the findings of the case.

PMID- 23865587
TI  - Analysis of the proteome of Saccharomyces cerevisiae for methylarginine.
AB  - Arginine methylation is a post-translational modification that has been
      implicated in a plethora of cellular processes. In the present manuscript, using
      two antimethylarginine antibodies and combinatorial deletion mutants of arginine
      methyltransferases, we found evidence of widespread arginine methylation in the
      Saccharomyces cerevisiae proteome. Immunoprecipitation was used for enrichment of
      methylarginine-containing proteins, which were identified via tandem mass
      spectrometry. From this, we identified a total of 90 proteins, of which 5 were
      previously known to be methylated. The proteins identified were involved in known
      methylarginine-associated biological functions such as RNA processing, nuclear
      transport, carbohydrate metabolic process, GMP biosynthetic process and protein
      folding. Through in vivo methylation by the incorporation of [3H]-methyl groups,
      we validated the methylation of 7 proteins (Ded1, Imd4, Lhp1, Nop1, Cdc11, Gus1,
      Pob3). By LC-MS/MS, we then confirmed a total of 15 novel methylarginine sites on
      5 proteins (Ded1, Lhp1, Nop1, Pab1, and Ugp1). By examination of methylation on
      proteins from the triple knockout of methyltransferases Hmt1, Hsl7, Rmt2, we
      present evidence for the existence of additional unidentified arginine
      methyltransferases in the Saccharomyces cerevisiae proteome.

PMID- 23865588
TI  - Stress-induced elevation of oxytocin in maltreated children: evolution,
      neurodevelopment, and social behavior.
AB  - Child maltreatment often has a negative impact on the development of social
      behavior and health. The biobehavioral mechanisms through which these adverse
      outcomes emerge, however, are not clear. To better understand the ways in which
      early life adversity affects subsequent social behavior, changes in the
      neuropeptide oxytocin (OT) in children (n = 73) aged 8.1-11.5 years following a
      laboratory stressor were examined. Girls with histories of physical abuse have
      higher levels of urinary OT and lower levels of salivary cortisol following the
      stressor when compared to controls. Abused and control boys, however, do not
      differ in their hormonal responses. These data suggest that early adversity may
      disrupt the development of the stress regulation system in girls by middle
      childhood.

PMID- 23865590
TI  - Managing dyspepsia in the young adult patient: effects of different tests for
      Helicobacter pylori in a "test-and-scope" approach.
AB  - AIM: To evaluate how different methods for the detection of Helicobacter pylori
      influence on a "test, score and scope" decision approach in young dyspeptic
      patients. RESULTS: Complete data from 341 patients (52.2% males) were analyzed.
      One hundred and ten (32%) were H. pylori-positive by definition. The rapid
      serology test was true-positive in 64 patients, false-positive in 8, and false
      negative in 46. For the EIA IgG serology test, the corresponding results were 99
      true-positive, 7 false-positive, and 11 false-negative. If the H. pylori fecal
      test or urea breath test had been applied, 108 (98%) and 107 (97%) positives
      would have been correctly detected, respectively, as well as 14 and 7 false
      positives. Models using test data in a setting of decreasing H. pylori prevalence
      show that test properties have increasing significance. CONCLUSIONS: In a
      selection strategy for young dyspeptics based on the detection of H. pylori, the
      choice of test should be made with caution. H. pylori fecal test would probably
      give the best basis for such selection.

PMID- 23865589
TI  - Screening bicyclic peptide libraries for protein-protein interaction inhibitors:
      discovery of a tumor necrosis factor-alpha antagonist.
AB  - Protein-protein interactions represent a new class of exciting but challenging
      drug targets, because their large, flat binding sites lack well-defined pockets
      for small molecules to bind. We report here a methodology for chemical synthesis
      and screening of large combinatorial libraries of bicyclic peptides displayed on
      rigid small-molecule scaffolds. With planar trimesic acid as the scaffold, the
      resulting bicyclic peptides are effective for binding to protein surfaces such as
      the interfaces of protein-protein interactions. Screening of a bicyclic peptide
      library against tumor necrosis factor-alpha (TNFalpha) identified a potent
      antagonist that inhibits the TNFalpha-TNFalpha receptor interaction and protects
      cells from TNFalpha-induced cell death. Bicyclic peptides of this type may
      provide a general solution for inhibition of protein-protein interactions. 

PMID- 23865591
TI  - On-demand hyoscine butylbromide for the treatment of self-reported functional
      cramping abdominal pain.
AB  - OBJECTIVE: Hyoscine butylbromide (HBB) has been used for 60 years to treat
      cramping abdominal pain, but scientific evidence to support on-demand use is
      limited. The aim of this study was to identify a meaningful efficacy end point
      that differentiates between the effects of HBB (20-100 mg/day) and placebo when
      used on demand. MATERIALS & METHODS: 175 patients were treated in a randomized,
      double-blind, placebo-controlled, two-arm parallel group study. After a 4-week
      run-in period, patients used HBB to treat 2 distinct episodes of abdominal pain
      associated with cramping (APC). Patients entered data into an electronic diary
      for up to 4 h/episode. Pain intensity was assessed using an 11-point numerical
      pain rating scale (NPRS). Patients were allowed to self-medicate with up to 4
      additional doses of HBB every 30 min. RESULTS: The adjusted mean difference for
      the change from baseline during the 4-h observation period for a reduction in
      abdominal pain was -0.7 (95% confidence interval (CI) -1.3, -0.1, p = 0.016) for
      episode 1 and -0.6 (95% CI -1.2, 0.0, p = 0.051) for episode 2. Patients in the
      HBB group recorded a clinically relevant reduction of at least 2 points on the
      NPRS (approximately 30% pain relief) earlier than patients in the placebo group
      (HBB: 45 min, placebo: 60 min). Reported adverse events were infrequent in both
      groups (10.2% and 10.3%). CONCLUSIONS: HBB is effective in the treatment of
      recurrent APC and is safe and well tolerated when used on demand. The change from
      baseline in the intensity of APC using the 11-point NPRS distinguished HBB from
      placebo.

PMID- 23865592
TI  - Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced
      mucositis.
AB  - BACKGROUND: Mucositis is a debilitating intestinal side effect of
      chemotherapeutic regimens. Probiotics have been considered a possible
      preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a
      newly identified probiotic, has been shown to partially alleviate mucositis
      induced by administration of the antimetabolite chemotherapy drug, methotrexate
      in rats; likely mediated through a mechanism of folate production. However, its
      effects against other classes of chemotherapy drug have yet to be determined.
      AIMS: The authors investigated the effects of TH-4 in a rat model of mucositis
      induced by the anthracycline chemotherapy drug, doxorubicin. METHODS:
      Gastrointestinal damage was induced in female Dark Agouti rats (148.3 +/- 1.5 g)
      by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily
      oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At
      day 6, rats were injected with either saline or doxorubicin. At kill, small
      intestinal tissues were collected for determination of sucrase and
      myeloperoxidase (MPO) activities and histological assessment. RESULTS: Body
      weight was significantly decreased by doxorubicin compared with normal controls
      (p < 0.05). Histological parameters, such as crypt depth and villus height, were
      also significantly decreased by doxorubicin. TH-4 partially prevented the loss of
      body weight induced by doxorubicin (2.3% compared with 4%), but provided no
      further therapeutic benefit. CONCLUSIONS: The minimal amelioration of doxorubicin
      induced mucositis by TH-4 further supports folate production as a likely
      mechanism of TH-4 action against methotrexate-induced mucositis. Further studies
      into TH-4 are required to confirm its applicability to other conventional
      chemotherapy regimens.

PMID- 23865593
TI  - Using wireless technology in clinical practice: does feedback of daily walking
      activity improve walking outcomes of individuals receiving rehabilitation post
      stroke? Study protocol for a randomized controlled trial.
AB  - BACKGROUND: Regaining independent ambulation is the top priority for individuals
      recovering from stroke. Thus, physical rehabilitation post-stroke should focus on
      improving walking function and endurance. However, the amount of walking
      completed by individuals with stroke attending rehabilitation is far below that
      required for independent community ambulation. There has been increased interest
      in accelerometer-based monitoring of walking post-stroke. Walking monitoring
      could be integrated within the goal-setting process for those with ambulation
      goals in rehabilitation. The feedback from these devices can be downloaded to a
      computer to produce reports. The purpose of this study is to determine the effect
      of accelerometer-based feedback of daily walking activity during rehabilitation
      on the frequency and duration of walking post-stroke. METHODS: Participants will
      be randomly assigned to one of two groups: feedback or no feedback. Participants
      will wear accelerometers daily during in- and out-patient rehabilitation and, for
      participants in the feedback group, the participants' treating physiotherapist
      will receive regular reports of walking activity. The primary outcome measures
      are the amount of daily walking completed, as measured using the accelerometers,
      and spatio-temporal characteristics of walking (e.g. walking speed). We will also
      examine goal attainment, satisfaction with progress towards goals, stroke self
      efficacy, and community-integration. DISCUSSION: Increased walking activity
      during rehabilitation is expected to improve walking function and community re
      integration following discharge. In addition, a focus on altering walking
      behaviour within the rehabilitation setting may lead to altered behaviour and
      increased activity patterns after discharge. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01521234.

PMID- 23865594
TI  - Design and validation of a supragenome array for determination of the genomic
      content of Haemophilus influenzae isolates.
AB  - BACKGROUND: Haemophilus influenzae colonizes the human nasopharynx as a
      commensal, and is etiologically associated with numerous opportunistic infections
      of the airway; it is also less commonly associated with invasive disease.
      Clinical isolates of H. influenzae display extensive genomic diversity and
      plasticity. The development of strategies to successfully prevent, diagnose and
      treat H. influenzae infections depends on tools to ascertain the gene content of
      individual isolates. RESULTS: We describe and validate a Haemophilus influenzae
      supragenome hybridization (SGH) array that can be used to characterize the full
      genic complement of any strain within the species, as well as strains from
      several highly related species. The array contains 31,307 probes that
      collectively cover essentially all alleles of the 2890 gene clusters identified
      from the whole genome sequencing of 24 clinical H. influenzae strains. The finite
      supragenome model predicts that these data include greater than 85% of all non
      rare genes (where rare genes are defined as those present in less than 10% of
      sequenced strains). The veracity of the array was tested by comparing the whole
      genome sequences of eight strains with their hybridization data obtained using
      the supragenome array. The array predictions were correct and reproducible for ~
      98% of the gene content of all of the sequenced strains. This technology was then
      applied to an investigation of the gene content of 193 geographically and
      clinically diverse H. influenzae clinical strains. These strains came from
      multiple locations from five different continents and Papua New Guinea and
      include isolates from: the middle ears of persons with otitis media and otorrhea;
      lung aspirates and sputum samples from pneumonia and COPD patients, blood
      specimens from patients with sepsis; cerebrospinal fluid from patients with
      meningitis, as well as from pharyngeal specimens from healthy persons.
      CONCLUSIONS: These analyses provided the most comprehensive and detailed
      genomic/phylogenetic look at this species to date, and identified a subset of
      highly divergent strains that form a separate lineage within the species. This
      array provides a cost-effective and high-throughput tool to determine the gene
      content of any H. influenzae isolate or lineage. Furthermore, the method for
      probe selection can be applied to any species, given a group of available whole
      genome sequences.

PMID- 23865595
TI  - Assessment of leishmanicidal and trypanocidal activities of aliphatic diamine
      derivatives.
AB  - Leishmanicidal and trypanocidal activity of seventeen lipophilic diamines was
      evaluated in vitro against Leishmania braziliensis, L. chagasi, and Trypanosoma
      cruzi. Twelve compounds presented anti-Leishmania and six showed anti-T. cruzi
      amastigote activity. Compound 14 (N-tetradecyl-1,4-butanediamine) was the most
      active against both L. braziliensis (IC50  = 2.6 MUm) and L. chagasi (IC50  = 3.0
      MUm) which showed a selectivity index (SI) >100. N-decyl-1,6-hexanediamine
      (compound 9) presented an IC50  = 1.6 MUm and SI >187 and was over six times more
      potent than the reference drug benznidazole against T. cruzi. Treatment of
      infected or uninfected macrophages with compounds 9 and 14 did not induce
      significant TNFalpha and NO production. Four compounds (15, 16, 22, and 23)
      inhibited 78.9%, 77.7%, 83.7%, and 70.1% of rTRLb activity, respectively, and
      compound 23 inhibited 73.3% of rTRTc activity at 100 MUm. A concentration
      dependent effect on mitochondrial membrane depolarization was observed in T.
      cruzi epimastigotes treated with compound 9, suggesting this mechanism may be
      involved in the trypanocidal effect. On the contrary, in L. braziliensis
      promastigotes treated with compound 14, no mitochondrial depolarization was
      observed. Our results demonstrate that N-decyl-1,6-hexanediamine and N-tetradecyl
      1,4-butanediamine are promising molecules for the development of novel leading
      compounds against T. cruzi and Leishmania spp., particularly given a possible
      alternative mechanism of action. 

PMID- 23865596
TI  - The protective effect of recombinant Lactococcus lactis oral vaccine on a
      Clostridium difficile-infected animal model.
AB  - BACKGROUND: Oral immunization with vaccines may be an effective strategy for
      prevention of Clostridium difficile infection (CDI). However, application of
      previously developed vaccines for preventing CDI has been limited due to various
      reasons. Here, we developed a recombinant Lactococcus lactis oral vaccine and
      evaluated its effect on a C. difficile-infected animal model established in
      golden hamsters in attempt to provide an alternative strategy for CDI prevention.
      METHODS: Recombinant L. lactis vaccine was developed using the pTRKH2 plasmid, a
      high-copy-number Escherichia coli-L. shuttle vector: 1) L. lactis expressing
      secreted proteins was constructed with recombinant pTRKH2 (secreted-protein
      plasmid) carrying the Usp45 signal peptide (SPUsp45), nontoxic adjuvanted tetanus
      toxin fragment C (TETC), and 14 of the 38 C-terminal repeats (14CDTA) of nontoxic
      C. difficile toxin A (TcdA); and 2) L. lactis expressing secreted and membrane
      proteins was constructed with recombinant pTRKH2 (membrane-anchored plasmid)
      carrying SPUsp45, TETC, 14CDTA, and the cell wall-anchored sequence of protein M6
      (cwaM6). Then, 32 male Syrian golden hamsters were randomly divided into 4 groups
      (n = 8 each) for gavage of normal saline (blank control) and L. lactis carrying
      the empty shuttle vector, secreted-protein plasmid, and membrane-anchored
      plasmid, respectively. After 1-week gavage of clindamycin, the animals were
      administered with C. difficile spore suspension. General symptoms and intestinal
      pathological changes of the animals were examined by naked eye and microscopy,
      respectively. Protein levels of anti-TcdA IgG/IgA antibodies in intestinal tissue
      and fluid were analyzed by enzyme-linked immunosorbent assay (ELISA). A cell
      culture cytotoxicity neutralization assay was done by TcdA treatment with or
      without anti-TcdA serum pre-incubation or treatment. Apoptosis of intestinal
      epithelial cells was examined by flow cytometry (FL) assay. Expression of mucosal
      inflammatory cytokines in the animals was detected by polymer chain reaction
      (PCR) assay. RESULTS: After the C. difficile challenge, the animals of control
      group had severe diarrhea symptoms on day 1 and all died on day 4, indicating
      that the CDI animal model was established in hamster. Of the 3 immunization
      groups, secreted-protein and membrane-anchored plasmid groups had significantly
      lower mortalities, body weight decreases, and pathological scores, with higher
      survival rate/time than the empty plasmid group (P < 0.05). The tilter of IgG
      antibody directed against TcdA was significantly higher in serum and intestinal
      fluid of secreted-protein and membrane-anchored plasmid groups than in the empty
      plasmid group (P < 0.05) while the corresponding titer of IgA antibody directed
      against TcdA had no substantial differences (P > 0.05). The anti-TcdA serum of
      membrane-anchored plasmid group neutralized the cytotoxicity of 200 ng/ml TcdA
      with the best protective effect achieved by anti-TcdA serum pre-incubation. The
      incidences of TcdA-induced death and apoptosis of intestinal epithelial cells
      were significantly reduced by cell pre-incubation or treatment with anti-TcdA
      serum of membrane-anchored plasmid group (P < 0.05). MCP-1, ICAM-1, IL-6, and Gro
      1 mRNA expression levels were the lowest in cecum tissue of the membrane-anchored
      groups compared to the other groups. CONCLUSION: Recombinant L. lactis live
      vaccine is effective for preventing CDI in the hamster model, thus providing an
      alternative for immunization of C. difficile-associated diseases.

PMID- 23865597
TI  - First quantification of alpha-Gal epitope in current glutaraldehyde-fixed heart
      valve bioprostheses.
AB  - BACKGROUND: Glutaraldehyde fixation does not guarantee complete tissue
      biocompatibility in current clinical bioprosthetic heart valves (BHVs).
      Particularly, circulating anti-alphaGal human antibodies increase significantly
      from just 10 days after a BHV implantation. The inactivation of such epitope
      should be mandatory to meet the requirements for a perspectively safe clinical
      application; nevertheless, its quantitative assessment in commercially available
      BHVs has never been carried out. METHODS: In this investigation, seven different
      models of BHVs were tested. The number of epitopes was determined with reference
      to a standard alphaGal source by an ELISA test. The presence of xenoantigen was
      subsequently confirmed by immunofluorescence analysis. Porcine tissue, knockout
      for the alphaGal epitopes, was used as negative control. RESULTS: EpicTM valve
      was the only model among those tested, in which the alphaGal antigen appeared to
      be completely shielded. Composite TrifectaTM valve exhibited conflicting results:
      cusps of bovine pericardial tissue were devoid of reactive alphaGal epitopes,
      while the stent cover strip of porcine pericardium still maintained 30% of active
      antigens originally present in native tissue. All other tested BHVs express an
      alphaGal amount not significantly different from that exhibited by porcine
      Mosaic((r)) valve (5.2 +/- 0.6 * 10(10) each 10 mg of tissue). CONCLUSIONS: For
      the first time, the quantitative evaluation of the alphaGal epitope in heart
      valve bioprostheses, already in clinical practice for about 40 yrs, was finally
      determined. Such quantification might provide indications of biocompatibility
      relevant for the selection of bioprosthetic devices and an increase in the
      confidence of the patient. It might become a major quality control tool in the
      production and redirection of future investigation in the quest for alphaGal-free
      long-lasting substitutes.

PMID- 23865598
TI  - Steric effects in peptide and protein exchange with activated disulfides.
AB  - Disulfide exchange is an important bioconjugation tool, enabling chemical
      modification of peptides and proteins containing free cysteines. We previously
      reported the synthesis of a macromer bearing an activated disulfide and its
      incorporation into hydrogels. Despite their ability to diffuse freely into
      hydrogels, larger proteins were unable to undergo in-gel disulfide exchange. In
      order to understand this phenomenon, we synthesized four different activated
      disulfide-bearing model compounds (Mn = 300 Da to 10 kDa) and quantified their
      rate of disulfide exchange with a small peptide (glutathione), a moderate-sized
      protein (beta-lactoglobulin), and a large protein (bovine serum albumin) in four
      different pH solutions (6.0, 7.0, 7.4, and 8.0) to mimic biological systems. Rate
      constants of exchange depend significantly on the size and accessibility of the
      thiolate. pH also significantly affects the rate of reaction, with the faster
      reactions occurring at higher pH. Surprisingly, little difference in exchange
      rates is seen between macromolecular disulfides of varying size (Mn = 2 kDa - 10
      kDa), although all undergo exchange more slowly than their small molecule
      analogue (MW = 300 g/mol). The maximum exchange efficiencies (% disulfides
      exchanged after 24 h) are not siginificantly affected by thiol size or pH, but
      somewhat affected by disulfide size. Therefore, while all three factors
      investigated (pH, disulfide size, and thiolate size) can influence the exchange
      kinetics and extent of reaction, the size of the thiolate and its accessibility
      plays the most significant role.

PMID- 23865599
TI  - Effect of molecular size and particle shape on the terahertz absorption of a
      homologous series of tetraalkylammonium salts.
AB  - The absorption coefficient and refractive index have been measured for a
      homologous series of tetraalkylammonium bromides over the frequency range 0.3-5.5
      THz. Spectral features are found to shift to lower frequencies as the molecular
      mass is increased, as expected. However, to understand the detailed structure of
      the observed spectral features, density functional perturbation theory
      calculations have been performed on the first four crystalline compounds in the
      series. From these calculations, we find that each spectrum is dominated by three
      translatory modes involving asymmetric motion of the ammonium cation and bromine
      counterion, although the overall number of active modes increases with increasing
      molecular size. The experimentally observed absorption is not completely
      described by the infrared active phonon modes alone. We show that it is also
      necessary to include the coupling of the phonon modes with the macroscopic field
      generated by the collective displacement of the vibrating ions, and we have
      applied an effective medium theory, which accounts for particle shape to allow
      for this effect in the calculation of the terahertz spectra. 

PMID- 23865600
TI  - Comparison of learning ability and memory retention in altricial (Bengalese
      finch, Lonchura striata var. domestica) and precocial (blue-breasted quail,
      Coturnix chinensis) birds using a color discrimination task.
AB  - The present study sought to assess the potential application of avian models with
      different developmental modes to studies on cognition and neuroscience. Six
      altricial Bengalese finches (Lonchura striata var. domestica), and eight
      precocial blue-breasted quails (Coturnix chinensis) were presented with color
      discrimination tasks to compare their respective faculties for learning and
      memory retention within the context of the two developmental modes. Tasks
      consisted of presenting birds with discriminative cues in the form of colored
      feeder lids, and birds were considered to have learned a task when 80% of their
      attempts at selecting the correctly colored lid in two consecutive blocks of 10
      trials were successful. All of the finches successfully performed the required
      experimental tasks, whereas only half of the quails were able to execute the same
      tasks. In the learning test, finches required significantly fewer trials than
      quails to learn the task (finches: 13.5 +/- 9.14 trials, quails: 45.8 +/- 4.35
      trials, P < 0.05), with finches scoring significantly more correct responses than
      quails (finches: 98.3 +/- 4.08%, quails: 85.0 +/- 5.77% at the peak of the
      learning curve). In the memory retention tests, which were conducted 45 days
      after the learning test, finches retained the ability to discriminate between
      colors correctly (95.0 +/- 4.47%), whereas quails did not retain any memory of
      the experimental procedure and so could not be tested. These results suggested
      that altricial and precocial birds both possess the faculty for learning and
      retaining discrimination-type tasks, but that altricial birds perform better than
      precocial birds in both faculties. The present findings imply that developmental
      mode is an important consideration for assessing the suitability of bird species
      for particular experiments. 

PMID- 23865601
TI  - Outcomes of a vision screening program for underserved populations in the United
      States.
AB  - PURPOSE: To evaluate which components of a vision screening process are most
      effective in identifying individuals who need eye care services. METHODS:
      Subjects visiting a free health clinic were screened using visual acuity and a
      questionnaire. Persons who failed screening were referred for a professional eye
      examination. RESULTS: A total of 1380 of 3004 screened persons (46%) screened
      positive on question(s) or distance visual acuity; 81% of screened positives were
      referred for an eye exam, <50% of the positives attended the examination, and one
      third had >=1 problem requiring intervention or monitoring. The most common
      problem was distance refractive error that, once corrected, improved vision by
      two or more lines, followed by glaucoma or glaucoma suspect (8.9%), visually
      significant cataract (7.2%), and diabetic retinopathy (2.5%). Ninety-four
      subjects who screened negative ("normal") were examined; nearly half of these had
      2+ lines of visual acuity improvement with refraction (from 20/40 or 20/32 to
      20/20). Sensitivity for detecting specific eye conditions varied substantially,
      ranging from 0-83% for individual screening questions. Time since last exam and
      distance acuity <20/50 were the most sensitive questions for visually significant
      cataract; however, their specificity was low. No combination of questions and
      acuity testing had both high sensitivity and specificity. CONCLUSIONS: Vision
      problems requiring intervention were common among this relatively young
      population, but no combination of screening questions and vision testing proved
      effective for screening. More than half of those who screened positive never
      showed for an examination, indicating that on-site eye exams might be more
      effective.

PMID- 23865602
TI  - Prevalence and associated risk indicators of retinopathy in a rural Bangladeshi
      population with and without diabetes.
AB  - PURPOSE: To determine the prevalence of retinopathy among people with normal and
      abnormal glucose metabolism in a remote rural community of Bangladesh, and to
      identify the associated risk indicators for developing retinopathy in this
      population. METHODS: A population-based cross-sectional study was conducted
      through screening in camp settings, which included a total of 836 participants
      (468 male and 368 female) aged 30 years or over. Retinopathy was determined by
      fundus photography. Anthropometric measures (body mass index and waist-to-hip
      ratio), oral glucose tolerance, glycosylated hemoglobin (HbA1c), blood pressure,
      lipid profile, serum creatinine and urine albumin creatinine ratio (UACR) were
      measured. Logistic regression analysis was used with adjustment for potential
      confounders. RESULTS: The overall prevalence of retinopathy was 5.4% (95%
      confidence interval, CI, 3.9-6.9). The prevalence rates of retinopathy among
      diabetic, impaired glucose regulation and non-diabetic subjects were 21.6%, 13%
      and 3.5%, respectively. Adjusted odds ratios for retinopathy were 2.53 (95% CI
      1.52-5.41) for abnormal glucose metabolism and 1.98 (95% CI 1.17-5.63), 1.74 (95%
      CI 1.09-3.02) and 1.63 (95% CI 1.08-3.12) for hypertension, HbA1c and UACR,
      respectively. Additionally, age, body mass index, triglyceride and total
      cholesterol were also found to be significant independent risk indicators for the
      occurrence of retinopathy in this population. CONCLUSION: A high prevalence of
      retinopathy was observed in this rural Bangladeshi population. In addition to
      blood glucose control for diabetes, screening for hypertension, obesity,
      hyperlipidemia and proteinuria as well as adequate treatment of these risk
      indicators may prevent retinopathy in rural Bangladeshi populations.

PMID- 23865603
TI  - Prevalence and etiology of amblyopia in Southern India: results from screening of
      school children aged 5-15 years.
AB  - PURPOSE: To determine the prevalence and etiology of amblyopia in school
      children. METHODS: A total of 4020 school children aged between 5 and 15 years
      were screened in a population-based, cross-sectional study. Best corrected visual
      acuity and detailed ophthalmic evaluation were performed in all participants.
      Amblyopia associated with degraded visual input due to high refractive error was
      labeled ametropic amblyopia. Anisometropic amblyopia was diagnosed in
      participants with interocular refractive error difference >=1 diopter. Strabismic
      amblyopia included that due to conflicting visual inputs between the eyes due to
      squint. Stimulus deprivation amblyopia was defined as amblyopia due to
      obstruction of the visual axis. RESULTS: Prevalence of amblyopia was 1.1% (n =
      44). The number of boys with amblyopia (n = 25, 57%) was slightly higher than the
      number of girls with amblyopia (n = 19, 43%; p = 0.6). A total of 28 (63.7%)
      children had mild to moderate amblyopia, whereas 16 (36.3%) had severe amblyopia.
      Underlying amblyogenic causes were ametropia (50%), anisometropia (40.9%),
      strabismus (6.8%), visual deprivation (4.5%) and combined causes (2.2%). No
      statistically significant difference was noted in the prevalence of amblyopia
      between rural (1.2%) and urban (0.9%) children (p = 0.5). CONCLUSION: In this
      study, the prevalence of amblyopia was 1.1% of the school children. Ametropia and
      anisometropia were the most common causes of amblyopia. We did not find any
      significant difference in amblyopia prevalence between rural and urban school
      children.

PMID- 23865604
TI  - Vision screening in children entering school: Eskisehir, Turkey.
AB  - PURPOSE: To report vision screening results among school children in Eskisehir,
      Turkey. METHODS: Vision screening was performed in 7- to 8-year-old school
      children in November and December 2011. Best-corrected visual acuity (BCVA)
      assessment, cover test, and autorefractometer measurement under cycloplegia were
      performed. Spherical equivalent <=-0.50 diopters (D) was considered to be myopic,
      while spherical equivalent >0.75 D was considered to be hypermetropic.
      Astigmatism was defined as a cylinder power >=0.75 D. Regression analysis was
      used to determine the likelihood of having BCVA <=0.8 Snellen (versus having BCVA
      >0.8 Snellen) in the presence of independent variables. RESULTS: A total of 709
      children were included. The prevalence rates of myopia, hypermetropia, and
      astigmatism were 22.6%, 10.6%, and 11.0%, respectively. Overall, 145 children
      (20.4%) needed spectacles, but only 65 of these were wearing them. The prevalence
      of children who required spectacles for myopia <=-3.00 D and spectacles for
      hypermetropia >=3.00 D were 0.8% and 1.0%, respectively. The prevalence of BCVA
      <= 0.8 Snellen was 56/709 (7.9%). In 39/709 (5.5%) of children, amblyopia was
      present; strabismus (14/56), isometropia (14/56), and anisometropia (11/56) were
      the etiologies. Strabismus was diagnosed in 18 children (2.5%). Anisometropia,
      strabismus, hypermetropia, and astigmatism were associated with BCVA <= 0.8
      Snellen (odds ratio, OR, 6.32, 39.18, 5.47, 5.17, respectively; p = 0.0001 for
      all ORs). CONCLUSIONS: Myopia and amblyopia rates in Eskisehir were high among
      school children. The need for a national large-scale vision screening program for
      children that includes diverse regions of Turkey is apparent.

PMID- 23865605
TI  - Development and evaluation of a Chinese version of the Adult Strabismus
      Questionnaire (AS-20).
AB  - PURPOSE: The 20-item Adult Strabismus Quality of Life Questionnaire (AS-20) was
      developed in the United States to assess health-related quality of life (HRQOL)
      of adult patients with strabismus. At present, no questionnaire is available for
      assessing HRQOL specifically for adult patients with strabismus in China. A
      Chinese version of the AS-20 (CAS-20) was developed and its reliability and
      validity evaluated in adult patients with strabismus in China. METHODS: The AS-20
      was translated into Chinese. A total of 102 adults with strabismus and 102
      visually healthy adult controls were recruited to answer the 5-level Likert items
      of the CAS-20. Demographic (age and sex) and clinical data of the recruited
      subjects were documented. Internal consistency, test-retest reliability,
      correlations between items and their respective subscale, and construct validity
      were evaluated to assess questionnaire reliability and validity. RESULTS: The
      number of responses for each item was calculated, as well as individual items'
      correlation with their respective subscale. Cronbach's alpha coefficient for the
      two subscales and the CAS-20 were satisfactory (0.846, 0.819, 0.883,
      respectively). The intra-class correlation coefficient for test-retest
      reliability was 0.723-0.862. Patients with strabismus had significantly lower
      scores on the CAS-20 than controls. Factor analysis identified six principal
      factors, and could be grouped into two subscales. The results supported the
      construct validity of the CAS-20. CONCLUSION: The CAS-20 presented satisfactory
      reliability and validity in our study. It is suggested that the questionnaire can
      be applied in clinical trials or research for Chinese patients with strabismus.

PMID- 23865606
TI  - Knowledge and attitudes about corneal ulceration among residents in a county of
      Shandong Province, China.
AB  - PURPOSE: To investigate knowledge, attitudes and status of health education about
      corneal ulceration among residents in Shouguang, a county of Shandong Province,
      China. METHODS: A cross-sectional survey was conducted in October 2010, and 2700
      residents aged 18-60 years were selected by multi-stage sampling to answer a
      questionnaire assessing knowledge, attitudes and status of health education about
      corneal ulceration. Influencing factors for knowledge and attitudes were
      evaluated with a chi(2) test and logistic regression analyses. RESULTS: Among all
      2440 participants, 37.4% had heard of corneal ulceration. Of these, 72.5% knew
      corneal trauma might cause corneal ulceration, 37.6% knew corneal ulceration
      might cause blindness and 52.2% had received health education on corneal
      ulceration. Of all participants, 55.1% thought they would not immediately seek
      help if corneal trauma occurred and 90.6% would like to receive health education
      on corneal ulceration. While sex, age, occupation, education level and contact
      lens wear were influencing factors for knowledge of corneal ulceration (all p <
      0.05), sex, age, income and contact lens wear were associated with participants'
      willingness to seek help for corneal trauma (all p < 0.05). CONCLUSIONS: There
      was a lack of knowledge and awareness about corneal ulceration among residents in
      Shouguang. Health education on corneal ulceration was limited, and should target
      high risk populations such as males, older people, farmers and workers, people
      with lower education, people with lower incomes and contact lens wearers. Health
      education should also focus on addressing the importance of timely treatment,
      encouraging people to seek help immediately and actively after corneal trauma.

PMID- 23865607
TI  - R2PI spectroscopy of aromatic molecules produced in an ethylene-rich flame.
AB  - Laser spectroscopy, combined with mass spectrometry, was applied to study the
      spectra of aromatic molecules produced in a premixed ethylene-rich flat flame.
      These studies produce new gas-phase electronic spectra of polyaromatic compounds,
      which ultimately will guide the understanding of the chemical processes that lead
      to polycyclic aromatic hydrocarbon (PAH) growth or PAH formation locking.
      Resonant two-photon ionization (R2PI) spectra of all species detectable in a
      specific fuel-rich flame were recorded simultaneously during a single scan of the
      laser wavelength, within the 220-330 nm range. Comparison with spectra available
      in the literature allowed us to identify 16 aromatic species. In the PAH forming
      region of this flame, we found that the main PAHs are accompanied by a great
      diversity of other species, including in particular various side-chains on
      aromatic networks. We also show that this technique allows, at least in some
      cases, to distinguish between different isomers associated with the same mass
      peak, although the extracted PAHs are only cooled down to room temperature. 

PMID- 23865609
TI  - An adherence based cost-consequence model comparing bimatoprost 0.01% to
      bimatoprost 0.03%.
AB  - OBJECTIVES: Estimate the long-term direct medical costs and clinical consequences
      of improved adherence with bimatoprost 0.01% compared to bimatoprost 0.03% in the
      treatment of glaucoma. METHODS: A cost-consequence model was constructed from the
      perspective of a US healthcare payer. The model structure included three
      adherence levels (high, moderate, low) and four mean deviation (MD) defined
      health states (mild, moderate, severe glaucoma, blindness) for each adherence
      level. Clinical efficacy in terms of IOP reduction was obtained from the
      randomized controlled trial comparing bimatoprost 0.01% with bimatoprost 0.03%.
      Medication adherence was based on observed 12 month rates from an analysis of a
      nationally representative pharmacy claims database. Patients with high, moderate
      and low adherence were assumed to receive 100%, 50% and 0% of the IOP reduction
      observed in the clinical trial, respectively. Each 1 mmHg reduction in IOP was
      assumed to result in a 10% reduction in the risk of glaucoma progression. Worse
      glaucoma severity health states were associated with higher medical resource
      costs. Outcome measures were total costs, proportion of patients who progress and
      who become blind, and years of blindness. Deterministic sensitivity analyses were
      performed on uncertain model parameters. RESULTS: The percentage of patients
      progressing, becoming blind, and the time spent blind slightly favored
      bimatoprost 0.01%. Improved adherence with bimatoprost 0.01% led to higher costs
      in the first 2 years; however, starting in year 3 bimatoprost 0.01% became less
      costly compared to bimatoprost 0.03% with a total reduction in costs reaching
      US$3433 over a lifetime time horizon. Deterministic sensitivity analyses
      demonstrated that results were robust, with the majority of analyses favoring
      bimatoprost 0.01%. Application of 1 year adherence and efficacy over the long
      term are limitations. CONCLUSIONS: Modeling the effect of greater medication
      adherence with bimatoprost 0.01% compared with bimatoprost 0.03% suggests that
      differences may result in improved economic and patient outcomes.

PMID- 23865610
TI  - Preliminary study on the effect of heated surfaces upon bloodstain pattern
      analysis.
AB  - Bloodstain pattern analysis (BPA) involves the interpretation of distinct blood
      patterns found at crime scenes following a violent act. In this paper, we
      explored for the first time the effects of surface temperatures upon blood
      impacting a horizontal surface (steel) with its implications in BPA explored.
      Specific surface temperatures were explored over the range 24-250 degrees C which
      relate to the four major boiling regimes of liquid media; natural convection,
      nucleate boiling, transition boiling, and film boiling, where a series of blood
      drops tests were performed at varying impact velocities. Blood was found to
      separate into its components at temperatures of 50 degrees C+, displayed as
      temperature induced blood rings, where a single secondary and a series of further
      inner rings are exhibited. This consequently led to the development of a new
      constant Cd heated expressing the decrease in spread factor (D(s)/D(o)) at the
      secondary ring.

PMID- 23865611
TI  - Adolescents' selective visual attention for high-status peers: the role of
      perceiver status and gender.
AB  - Previous research has shown that adolescents' attention for a peer is determined
      by the peer's status. This study examined how it is also determined by the status
      of the perceiving adolescent, and the gender of both parties involved (perceiver
      and perceived). Participants were 122 early adolescents (M age = 11.0 years) who
      completed sociometric measures and eye-tracking recordings of visual fixations at
      pictures of high-status (popular) and low-status (unpopular) classmates.
      Automatic attention (first-gaze preference) and controlled attention (total gaze
      time) were measured. Target popularity was associated with both measures of
      attention. These associations were further moderated by perceiver popularity and
      perceiver and target gender. Popular adolescents attracted attention especially
      from other popular adolescents. Popular boys attracted attention especially from
      girls. 

PMID- 23865613
TI  - Bifunctional sucrose phosphate synthase/phosphatase is involved in the sucrose
      biosynthesis by Methylobacillus flagellatus KT.
AB  - The aerobic obligate methylotroph Methylobacillus flagellatus KT was shown to
      synthesize sucrose in the presence of 0.5-2% NaCl in the growth medium. In the
      genome of this bacterium, an open reading frame (ORF) encoding a predicted 84-kD
      polypeptide homologous to the plant and cyanobacterial sucrose phosphate
      synthases (SPSs) was found. Using heterologous expression of the putative sps
      gene in Escherichia coli, followed by affinity chromatography, pure recombinant
      protein SPS-His6 was obtained. The enzyme catalyzed two reactions: conversion of
      fructose 6-phosphate and UDP-glucose into sucrose 6-phosphate and hydrolysis of
      sucrose 6-phosphate to sucrose. The bifunctional sucrose phosphate
      synthase/phosphatase (SPS/SPP) was a 340 kDa homotetrameric Mg(2+) -dependent
      enzyme activated by fructose 1,6-phosphate2 and ATP but inhibited by glucose 6
      phosphate, fructose 1-phosphate, AMP and inorganic phosphate. The amino acid
      sequence of the protein had a C-terminal domain homologous to SPPs. This
      correlated with the absence of the spp gene in the M. flagellatus chromosome. The
      ORFs homologous to the M. flagellatus SPS were found in the genomes of another
      obligate methylotroph Methylovorus glucosetrophus as well as the lithoautotrophic
      bacteria Acidithiobacillus ferrooxidans, Nitrosomonas europaea and Nitrosospira
      multiformis whose genomes lacked the spp genes. Thus, data extending the
      knowledge of biochemical properties of bacterial SPSs have been obtained. 

PMID- 23865614
TI  - Pharmacists and maternal-fetal medicine: development of a tool to characterize
      knowledge and current clinical practice.
AB  - OBJECTIVE: To develop a knowledge assessment tool to assess baseline knowledge
      and current practice regarding maternal-fetal medicine. METHODS: A literature
      search was complemented with categorization of questions under five predefined
      domains related to maternal-fetal medicine. The final questionnaire was sent for
      expert review, cultural adaptation, and piloting, with feedback incorporated
      accordingly. RESULTS: A questionnaire was developed consisting of questions
      pertaining to demographics, knowledge, and current practice. CONCLUSIONS: This
      tool is of interest to researchers, educators, and clinicians aiming to assess
      baseline knowledge, current curricula (both entry-to-practice and graduate) and
      continuing education opportunities for practicing pharmacists.

PMID- 23865615
TI  - Selective synthesis of Co8S15 cluster in bowl-shaped template of the
      pentaaryl[60]fullerene ligand.
AB  - A cobalt-sulfur cluster Co8S15 with molecular formula of (C60Ar5)-Co8S15(n)Bu2
      (C60Ar5) (Ar = 4-(t)BuC6H4) was selectively synthesized from a
      pentaaryl[60]fullerene cobalt trisulfide complex, (eta(5)-C60Ar5)CoS3. The bowl
      shaped steric templating fullerene ligand, as well as the metastable cobalt
      trisulfide moiety, played important roles in the exclusive cluster formation. X
      ray crystallography, as well as electrochemical, time-resolved photophysical, and
      magnetic, measurements revealed a mixed-valence cluster with six cobalt(III) and
      two high-spin cobalt(II) centers showing reversible redox behavior and
      photoinduced charge separation. 

PMID- 23865616
TI  - Immune gene expression profiling of Proliferative Kidney Disease in rainbow trout
      Oncorhynchus mykiss reveals a dominance of anti-inflammatory, antibody and T
      helper cell-like activities.
AB  - The myxozoan Tetracapsuloides bryosalmonae is the causative agent of
      Proliferative Kidney Disease (PKD) targeting primarily the kidney of infected
      fish where it causes a chronic lymphoid immunopathology. Although known to be
      associated with suppression of some cellular aspects of innate immunity and a
      prominent lymphocytic hyperplasia, there remains a considerable knowledge gap in
      our understanding of the underlying immune mechanisms driving PKD pathogenesis.
      To provide further insights, the expression profiles of a panel of
      innate/inflammatory and adaptive immune molecules were examined in rainbow trout
      Oncorhynchus mykiss following a natural exposure to the parasite. Relative to
      controls, fish with early to advanced stages of kidney pathology exhibited up
      regulation of the inflammatory cytokines interleukin (IL)-6 and IL-11, although
      remaining refractory towards genes indicative of macrophage activity.
      Antimicrobial peptides (AMPs) and anti-inflammatory markers, including
      cathelicidin (CATH) and IL-10 were markedly up-regulated during clinical disease.
      Up-regulation of adaptive immune molecules, including cell markers and antibody
      genes reflect the lymphocytic dominance of this disease and the likely importance
      of lymphocyte subsets in PKD pathogenesis. Up-regulation of T helper (TH) cell
      like response genes and transcription factors implies that T. bryosalmonae may
      elicit a complex interplay between TH cell subsets. This work, for the first time
      in the study of fish-myxozoan interactions, suggests that PKD pathogenesis is
      shaped by an anti-inflammatory phenotype, a profound B cell/antibody response and
      dysregulated TH cell-like activities. A better understanding of the functional
      roles of fish immune cells and molecules in PKD pathogenesis may facilitate
      future development of control measures against this disease.

PMID- 23865617
TI  - Photoprotection in the green tidal alga Ulva prolifera: role of LHCSR and PsbS
      proteins in response to high light stress.
AB  - Ulva prolifera, an intertidal macroalga, has to adapt to wide variations in light
      intensity, making this species particularly rewarding for studying the evolution
      of photoprotective mechanisms. Intense light induced increased non-photochemical
      quenching (NPQ) and stimulated de-epoxidation of xanthophyll cycle components,
      while DTT-treated samples had lower NPQ capacity, indicating that the xanthophyll
      cycle must participate in photoprotection. In this work, we found that the PsbS
      related NPQ was maintained in U. prolifera. According to analysed gene
      expression, both LhcSR and psbS were up-regulated in high light, suggesting that
      these two genes are light-induced. LHCSR and PsbS proteins were present at
      different light intensities and accumulated under high light conditions, and PsbS
      concentrations were higher than LHCSR, showing that the NPQ mechanism of U.
      prolifera is more dependent on PsbS protein concentration. Moreover, the level of
      both LHCSR and PsbS proteins was high even in the darkness, and neither the
      transcript level nor protein content of LhcSR and psbS genes varied significantly
      following short-term exposure to intense light. These findings suggest that this
      alga can modulate NPQ levels through regulation of the xanthophyll cycle and
      concentrations of PsbS and/or LHCSR. 

PMID- 23865618
TI  - Morphological and ribosomal DNA-based characterization of six Antarctic ciliate
      morphospecies from the Amundsen Sea with phylogenetic analyses.
AB  - We characterized six tintinnid ciliates from Antarctic waters using molecular
      markers and morphological traits: Amphorellopsis quinquealata, Codonellopsis
      gaussi, Cymatocylis convallaria, Cy. calyciformis, Cy. drygalskii, and
      Laackmanniella prolongata. The 100% similarity in SSU-ITS1-5.8S rDNA-ITS2-partial
      LSU rDNA sequences among Cy. convallaria, Cy. calyciformis, and Cy. drygalskii is
      supportive of synonymy. Codonellopsis gaussi and L. prolongata also showed high
      levels of similarity in SSU rDNA (99.83%) and the D2 domain of LSU rDNA (95.77%),
      suggesting that they are closely related. Phylogenetic analysis placed
      Cymatocylis in the Rhabdonellidae, Amphorellopsis in the Tintinnidae and L.
      prolongata/Co. gaussi within the Dictyocystidae. 

PMID- 23865620
TI  - The effects of fine-scale substratum roughness on diatom community structure in
      estuarine biofilms.
AB  - Benthic diatoms are a major component of biofilms that form on surfaces submerged
      in marine environments. Roughness of the underlying substratum affects the
      settlement of both diatoms and subsequent macrofouling colonizers. This study
      reports the effects of roughness on estuarine diatom communities established in
      situ in the Indian River Lagoon, FL, USA. Natural communities were established on
      acrylic panels with a range of surface roughnesses. Smoother substrata exhibited
      higher cell density, species richness, and diversity. Twenty-three of 58 species
      were found either exclusively or more abundantly on the smooth surfaces compared
      to one or both roughened treatments. The results suggest a greater ability of
      benthic diatoms to recruit and colonize smooth surfaces, which is probably
      explained by a higher degree of contact between the cells and the surface. 

PMID- 23865619
TI  - Multipotent mesenchymal stem cells from human subacromial bursa: potential for
      cell based tendon tissue engineering.
AB  - Rotator cuff injuries are a common clinical problem either as a result of overuse
      or aging. Biological approaches to tendon repair that involve use of scaffolding
      materials or cell-based approaches are currently being investigated. The cell
      based approaches are focused on applying multipotent mesenchymal stem cells
      (MSCs) mostly harvested from bone marrow. In the present study, we focused on
      characterizing cells harvested from tissues associated with rotator cuff tendons
      based on an assumption that these cells would be more appropriate for tendon
      repair. We isolated MSCs from bursa tissue associated with rotator cuff tendons
      and characterized them for multilineage differentiation in vitro and in vivo.
      Human bursa was obtained from patients undergoing rotator cuff surgery and cells
      within were isolated using collagenase and dispase digestion. The cells isolated
      from the tissues were characterized for osteoblastic, adipogenic, chondrogenic,
      and tenogenic differentiation in vitro and in vivo. The results showed that the
      cells isolated from bursa tissue exhibited MSCs characteristics as evidenced by
      the expression of putative cell surface markers attributed to MSCs. The cells
      exhibited high proliferative capacity and differentiated toward cells of
      mesenchymal lineages with high efficiency. Bursa-derived cells expressed markers
      of tenocytes when treated with bone morphogenetic protein-12 (BMP-12) and assumed
      aligned morphology in culture. Bursa cells pretreated with BMP-12 and seeded in
      ceramic scaffolds formed extensive bone, as well as tendon-like tissue in vivo.
      Bone formation was demonstrated by histological analysis and immunofluorescence
      for DMP-1 in tissue sections made from the scaffolds seeded with the cells.
      Tendon-like tissue formed in vivo consisted of parallel collagen fibres typical
      of tendon tissues. Bursa-derived cells also formed a fibrocartilagenous tissue in
      the ceramic scaffolds. Taken together, the results demonstrate a new source of
      MSCs with a high potential for application in tendon repair. 

PMID- 23865621
TI  - Enhanced photovoltaic effect in BiVO4 semiconductor by incorporation with an
      ultrathin BiFeO3 ferroelectric layer.
AB  - The photovoltaic effect of BiVO4 semiconductor was investigated by incorporating
      an ultrathin BiFeO3 ferroelectric layer. It is found that the ultrathin
      ferroelectric layer with strong self-polarization and high carrier density is
      desirable to enhance the photovoltaic effect and to manipulate the photovoltaic
      polarity of the semiconductors. The photovoltage increases by 5-fold to 1 V, and
      the photocurrent density increases by 2-fold to 140 MUA/cm(2), in which the
      photovoltage is the highest compared with the reported values in polycrystalline
      and epitaxial ferroelectric thin film solar cells. The mechanism for the observed
      effect is discussed on the basis of a polarization-induced Schottky-like barrier
      at the BiFeO3/fluorine doped tin oxide interface. Our work provides good guidance
      for fabrication of cost-effective semiconductor photovoltaic devices with high
      performance, and this kind of ultrathin ferroelectric film may also have
      promising applications in copper indium gallium selenide solar cell, dye
      sensitized TiO2 solar cell, lighting emitting diode, and other photoelectron
      related devices. 

PMID- 23865622
TI  - Aggregation-free gold nanoparticles in ordered mesoporous carbons: toward highly
      active and stable heterogeneous catalysts.
AB  - A coordination-assisted synthetic approach is reported here for the synthesis of
      highly active and stable gold nanoparticle catalysts in ordered mesoporous carbon
      materials using triblock copolymer F127 as a structure-directing agent, thiol
      containing silane as a coordination agent, HAuCl4 as a gold source, and phenolic
      resin as a carbon source. Upon carbonization, the gold precursor becomes reduced
      to form monodispersed Au nanoparticles of ca. 9.0 nm, which are entrapped or
      confined by the "rigid" mesoporous carbonaceous framework. Nanoparticle
      aggregation is inhibited even at a high temperature of 600  degrees C. After
      removal of the silica component, the materials possess the ordered mesostructure,
      high surface area (~1800 m(2)/g), large pore volume (~1.19 cm(3)/g), and uniform
      bimodal mesopore size (<2.0 and 4.0 nm). The monodispersed gold nanoparticles are
      highly exposed because of the interpenetrated bimodal pores in the carbon
      framework, which exhibit excellent catalytic performance. A completely selective
      conversion of benzyl alcohol in water to benzoic acid can be achieved at 90 
      degrees C and 1 MPa oxygen. Benzyl alcohol can also be quantitatively converted
      to benzoic acid at 60  degrees C even under an atmospheric pressure, showing
      great advantages in green chemistry. The catalysts are stable, poison resistant,
      and reusable with little activity loss due to metal leaching. The silane coupling
      agent played several functions in this approach: (1) coordinating with gold
      species by the thiol group to benefit formation of monodispersed Au
      nanoparticles; (2) reacting with phenolic resins by silanol groups to form
      relatively "rigid" composite framework; (3) pore-forming agent to generate
      secondary pores in carbon pore walls, which lead to higher surface area, larger
      pore volumes, and higher accessibility to to the gold nanoparticles. Complete
      removal of the silica component proves to have little effect on the catalytic
      performance of entrapped Au nanoparticles.

PMID- 23865625
TI  - Combining structure-based pharmacophore and in silico approaches to discover
      novel selective serotonin reuptake inhibitors.
AB  - Inhibition of human serotonin transporter (hSERT) has been reported to be a
      potent strategy for the treatment for depression. To discover novel selective
      serotonin reuptake inhibitors (SSRIs), a structure-based pharmacophore model
      (SBPM) was developed using the docked conformations of six highly active SSRIs.
      The best SBPM, consisting of four chemical features: two ring aromatics (RAs),
      one hydrophobic (HY), and one positive ionizable (PI), was further validated
      using Gunner-Henry (GH) scoring and receiver operating characteristic (ROC) curve
      methods. This well-validated SBPM was then used as a 3D-query in virtual
      screening to identify potential hits from National Cancer Institute (NCI)
      database. These hits were subsequently filtered by absorption, distribution,
      metabolism, excretion, and toxicity (ADMET) prediction and molecular docking, and
      their binding stabilities were validated by 20-ns MD simulations. Finally, only
      two compounds (NSC175176 and NSC705841) were identified as potential leads, which
      exhibited higher binding affinities in comparison with the paroxetine. Our
      results also suggest that cation-pi interaction plays a crucial role in
      stabilizing the hSERT-inhibitor complex. To our knowledge, the present work is
      the first structure-based virtual screening study for new SSRI discovery, which
      should be a useful guide for the rapid identification of novel therapeutic agents
      from chemical database. 

PMID- 23865624
TI  - Safety and efficacy of a lifestyle intervention for pregnant women to prevent
      excessive maternal weight gain: a cluster-randomized controlled trial.
AB  - BACKGROUND: Excessive gestational weight gain (GWG) is associated with short- and
      long-term health problems among mothers and their offspring. There is a strong
      need for effective intervention strategies targeting excessive GWG to prevent
      adverse outcomes. METHODS: We performed a cluster-randomized controlled
      intervention trial in eight gynecological practices evaluating the feasibility
      and effectiveness of a lifestyle intervention presented to all pregnant women;
      250 healthy, pregnant women were recruited for the study. The intervention
      program consisted of two individually delivered counseling sessions focusing on
      diet, physical activity, and weight monitoring. The primary outcome was the
      proportion of pregnant women exceeding weight gain recommendations of the
      Institute of Medicine (IOM). Secondary outcome variables were maternal weight
      retention and short-term obstetric and neonatal outcomes. RESULTS: The
      intervention resulted in a lower proportion of women exceeding IOM guidelines
      among women in the intervention group (38%) compared with the control group (60%)
      (odds ratio (OR): 0.5; 95% confidence interval (CI): 0.3 to 0.9) without
      prompting an increase in the proportion of pregnancies with suboptimal weight
      gain (19% vs. 21%). Participants in the intervention group gained significantly
      less weight than those in the control group. Only 17% of the women in the
      intervention group showed substantial weight retention of more than 5 kg compared
      with 31% of those in the control group at month four postpartum (pp) (OR: 0.5;
      95% CI: 0.2 to 0.9). There were no significant differences in obstetric and
      neonatal outcomes. CONCLUSIONS: Lifestyle counseling given to pregnant women
      reduced the proportion of pregnancies with excessive GWG without increasing
      suboptimal weight gain, and may exert favorable effects on pp weight retention.
      TRIAL REGISTRATION: German Clinical Trials Register DRKS00003801.

PMID- 23865626
TI  - Bowel necrosis following endovascular revascularization for chronic mesenteric
      ischemia: a case report and review of the literature.
AB  - BACKGROUND: Endovascular revascularization has recently been established as a
      less invasive treatment method for chronic mesenteric ischemia. However,
      intestinal necrosis caused by distal embolization following this procedure has
      not been emphasized. CASE PRESENTATION: The present report describes a 59-year
      old man who was treated with endovascular revascularization for chronic
      mesenteric ischemia. After the procedure, he was diagnosed with intestinal
      necrosis caused by distal embolization. Despite emergent bowel resection, he died
      on postoperative day 109. CONCLUSION: Although endovascular revascularization for
      chronic mesenteric ischemia is less invasive and may be suitable for high-risk
      patients, attention should be paid to avoid embolic complications that can cause
      intestinal infarction possibly leading to a fatal condition.

PMID- 23865627
TI  - Properties of alkaline-hydrolyzed waterfowl feather keratin.
AB  - The properties of hydrolyzed feather keratin (HFK) were compared to those of
      hydrolyzed wool keratin (HWK) with the aim of developing better ways to utilize
      feather keratin waste. Amino acid analysis showed that HFK contained more
      hydrophobic amino acids did than HWK. Although gel permeation chromatography
      indicated that HFK and HWK had more low-molecular weight peptides than their
      intact sources, Fourier transform infrared spectroscopy indicated that both
      hydrolyzed keratins retained their original secondary structure. The physical
      properties of HFK were evaluated by treating HFK to human hair fibers. HFK
      treatment enhanced significantly the surface hydrophobicity and strength of
      fibers, and HFK was more permeable into hair fibers. These results suggest that
      HFK is suitable for industrial applications to improve fibers. In addition, HFK
      may be suitable for raw material of products requiring both flexibility and
      hydrophobicity, such as films and biodegradable plastics. 

PMID- 23865623
TI  - Comparative genomics in acid mine drainage biofilm communities reveals metabolic
      and structural differentiation of co-occurring archaea.
AB  - BACKGROUND: Metal sulfide mineral dissolution during bioleaching and acid mine
      drainage (AMD) formation creates an environment that is inhospitable to most
      life. Despite dominance by a small number of bacteria, AMD microbial biofilm
      communities contain a notable variety of coexisting and closely related
      Euryarchaea, most of which have defied cultivation efforts. For this reason, we
      used metagenomics to analyze variation in gene content that may contribute to
      niche differentiation among co-occurring AMD archaea. Our analyses targeted
      members of the Thermoplasmatales and related archaea. These results greatly
      expand genomic information available for this archaeal order. RESULTS: We
      reconstructed near-complete genomes for uncultivated, relatively low abundance
      organisms A-, E-, and Gplasma, members of Thermoplasmatales order, and for a
      novel organism, Iplasma. Genomic analyses of these organisms, as well as
      Ferroplasma type I and II, reveal that all are facultative aerobic heterotrophs
      with the ability to use many of the same carbon substrates, including methanol.
      Most of the genomes share genes for toxic metal resistance and surface-layer
      production. Only Aplasma and Eplasma have a full suite of flagellar genes whereas
      all but the Ferroplasma spp. have genes for pili production. Cryogenic-electron
      microscopy (cryo-EM) and tomography (cryo-ET) strengthen these metagenomics-based
      ultrastructural predictions. Notably, only Aplasma, Gplasma and the Ferroplasma
      spp. have predicted iron oxidation genes and Eplasma and Iplasma lack most genes
      for cobalamin, valine, (iso)leucine and histidine synthesis. CONCLUSION: The
      Thermoplasmatales AMD archaea share a large number of metabolic capabilities. All
      of the uncultivated organisms studied here (A-, E-, G-, and Iplasma) are
      metabolically very similar to characterized Ferroplasma spp., differentiating
      themselves mainly in their genetic capabilities for biosynthesis, motility, and
      possibly iron oxidation. These results indicate that subtle, but important
      genomic differences, coupled with unknown differences in gene expression,
      distinguish these organisms enough to allow for co-existence. Overall this study
      reveals shared features of organisms from the Thermoplasmatales lineage and
      provides new insights into the functioning of AMD communities.

PMID- 23865628
TI  - Genetic structure of Kurtzmaniella cleridarum, a cactus flower beetle yeast of
      the Sonoran and Mojave Deserts: speciation by distance?
AB  - We studied 95 isolates of the yeast species Kurtzmaniella cleridarum recovered
      from nitidulid beetles collected in flowers of cacti of the Sonoran Desert of
      southern Arizona and the Mojave Desert of California. They were characterized on
      the basis of mating type and ten polymorphic DNA markers in relation to their
      geographic distribution. Although all loci appeared to be free of strong linkage,
      the recovered haplotypes represented but a small fraction of possible
      combinations, indicating that abundant asexual reproduction of local genotypes
      accounts for much of population growth, even though the yeast is capable of
      sexual recombination in nature. Much of the genetic differentiation took place at
      the local level, indicating that gene flow across the various localities is
      limited. However, a relationship exists between overall genetic differentiation
      and geography over long distances. We estimated that populations separated by c.
      1300 km would share no alleles in common and that such a separation might be
      enough to favor the onset of speciation. 

PMID- 23865629
TI  - Intramolecular charge transfer with crystal violet lactone in acetonitrile as a
      function of temperature: reaction is not solvent-controlled.
AB  - Intramolecular charge transfer (ICT) with crystal violet lactone (CVL) in the
      excited singlet state takes place in solvents more polar than n-hexane, such as
      ethyl acetate, tetrahydrofuran, and acetonitrile (MeCN). In these solvents, the
      fluorescence spectrum of CVL consists of two emission bands, from a locally
      excited (LE) and an ICT state. The dominant deactivation channel of the lowest
      excited singlet state is internal conversion, as the quantum yields of
      fluorescence (0.007) and intersystem crossing (0.015) in MeCN at 25  degrees C
      are very small. CVL is a weakly coupled electron donor/acceptor (D/A) molecule,
      similar to an exciplex (1)(A(-)D(+)). A solvatochromic treatment of the LE and
      ICT emission maxima results in the dipole moments MUe(LE) = 17 D and MUe(ICT) =
      33 D, much larger than those previously reported. This discrepancy is attributed
      to different Onsager radii and spectral fluorimeter calibration. The LE and ICT
      fluorescence decays of CVL in MeCN are double exponential. As determined by
      global analysis, the LE and ICT decays at 25  degrees C have the times tau2 = 9.2
      ps and tau1 = 1180 ps, with an amplitude ratio of 35.3 for LE. From these
      parameters, the rate constants ka = 106 * 10(9) s(-1) and kd = 3.0 * 10(9) s(-1)
      of the forward and backward reaction in the LE ? ICT equilibrium are calculated,
      resulting in a free enthalpy difference DeltaG of -8.9 kJ/mol. The amplitude
      ratio of the ICT fluorescence decay equals -1.0, which signifies that the ICT
      state is not prepared by light absorption in the S0 ground state, but originates
      exclusively from the directly excited LE precursor. From the temperature
      dependence of the fluorescence decays of CVL in MeCN (-45 to 75  degrees C),
      activation energies E(a) = 3.9 kJ/mol (LE -> ICT) and E(d) = 23.6 kJ/mol (ICT ->
      LE) are obtained, giving an enthalpy difference DeltaH (= E(a) - E(d)) of -19.7
      kJ/mol, and an entropy difference DeltaS = -35.5 J mol(-1) K(-1). These data show
      that the ICT reaction of CVL in MeCN is not barrierless. The ICT reaction time of
      9.2 ps is much longer than the mean solvent relaxation time of MeCN (0.26 ps),
      indicating, in contrast with earlier reports in the literature, that the reaction
      is not solvent controlled. This conclusion is supported by the observation of
      double exponential LE and ICT fluorescence with the same decay times.

PMID- 23865630
TI  - Striae distensae are characterized by distinct microstructural features as
      measured by non-invasive methods in vivo.
AB  - BACKGROUND: Stretch marks or striae distensae (SD) are characterized by epidermal
      atrophy following repeated over-stretching of the skin tissue. The objective of
      this study was to investigate the skin texture and microstructure of SD lesions
      compared to those of normal adjacent skin in vivo using non-invasive methods.
      METHODS: A population of 26 women and 3 men with SD were examined after giving
      written informed consent. Following clinical grading, skin replicas were
      collected, confocal microscopy was performed on SD lesions and healthy
      neighboring skin. Skin surface texture parameters were calculated using 3D image
      analysis of the skin replicas and epidermal and dermal microstructure were
      evaluated by analysis of the confocal images. In a parallel study, histological
      analysis was performed on 6 skin biopsies taken from abdominal reduction
      surgeries in areas where skin exhibited SD. RESULTS: Analysis of the skin surface
      texture showed that the SD area was more anisotropic and with higher skin
      roughness than the adjacent skin in terms of directions of skin microglyphics.
      Confocal microscopy demonstrated that SD were characterized by shallower dermal
      papillae (P < 0.05) and that dermal papillae height inversely correlated to the
      intensity of collagen alignment on the SD sites (P < 0.05). The histology
      findings confirmed the in vivo confocal microscopy findings. CONCLUSIONS: The
      skin structure of SD is qualitatively and quantitatively different compared to
      healthy skin. Altered skin relief reflects structural modifications in the
      dermis. Flattening of the dermal-epidermal junction maybe functionally related to
      the observed collagen fiber alignment. Observations by non-invasive methods were
      in line with the histological findings and therefore relevant in studies
      assessing the efficacy of SD treatment options.

PMID- 23865631
TI  - Polymer-grafted cellulose nanocrystals as pH-responsive reversible flocculants.
AB  - Cellulose nanocrystals (CNCs) are a sustainable nanomaterial with applications
      spanning composites, coatings, gels, and foams. Surface modification routes to
      optimize CNC interfacial compatibility and functionality are required to exploit
      the full potential of this material in the design of new products. In this work,
      CNCs have been rendered pH-responsive by surface-initiated graft polymerization
      of 4-vinylpyridine with the initiator ceric(IV) ammonium nitrate. The
      polymerization is a one-pot, water-based synthesis carried out under sonication,
      which ensures even dispersion of the cellulose nanocrystals during the reaction.
      The resultant suspensions of poly(4-vinylpyridine)-grafted cellulose nanocrystals
      (P4VP-g-CNCs) show reversible flocculation and sedimentation with changes in pH;
      the loss of colloidal stability is visible by eye even at concentrations as low
      as 0.004 wt %. The presence of grafted polymer and the ability to tune the
      hydrophilic/hydrophobic properties of P4VP-g-CNCs were characterized by Fourier
      transform infrared spectroscopy, elemental analysis, electrophoretic mobility,
      mass spectrometry, transmittance spectroscopy, contact-angle measurements,
      thermal analysis, and various microscopies. Atomic force microscopy showed no
      observable changes in the CNC dimensions or degree of aggregation after polymer
      grafting, and a liquid crystalline nematic phase of the modified CNCs was
      detected by polarized light microscopy. Controlled stability and wettability of
      P4VP-g-CNCs is advantageous both in composite design, where cellulose
      nanocrystals generally have limited dispersibility in nonpolar matrices, and as
      biodegradable flocculants. The responsive nature of these novel nanoparticles may
      offer new applications for CNCs in biomedical devices, as clarifying agents, and
      in industrial separation processes. 

PMID- 23865632
TI  - Simultaneous generation of gradients with gradually changed slope in a
      microfluidic device for quantifying axon response.
AB  - Over the past decades, various microfluidic devices have been developed to
      investigate the role of the molecular gradient in axonal development; however,
      there are very few devices providing quantitative information about the response
      of axons to molecular gradients with different slopes. Here, we propose a novel
      laminar-based microfluidic device enabling simultaneous generation of multiple
      gradients with gradually changed slope on a single chip. This device, with two
      asymmetrically designed peripheral channels and opposite flow direction, could
      generate gradients with gradually changed slope in the center channel, enabling
      us to investigate simultaneously the response of axons to multiple slope
      gradients with the same batch of neurons. We quantitatively investigated the
      response of axon growth rate and growth direction to substrate-bound laminin
      gradients with different slopes using this single-layer chip. Furthermore, we
      compartmented this gradient generation chip and a cell culture chip by a porous
      membrane to investigate quantitatively the response of axon growth rate to the
      gradient of soluble factor netrin-1. The results suggested that contacting with a
      molecular gradient would effectively accelerate neurites growth and enhance
      axonal formation, and the axon guidance ratio obviously increased with the
      increase of gradient slope in a proper range. The capability of generating a
      molecular gradient with continuously variable slopes on a single chip would open
      up opportunities for obtaining quantitative information about the sensitivity of
      axons and other types of cells in response to gradients of various proteins. 

PMID- 23865633
TI  - LOV-domain photoreceptor, encoded in a genomic island, attenuates the virulence
      of Pseudomonas syringae in light-exposed Arabidopsis leaves.
AB  - In Arabidopsis thaliana, light signals modulate the defences against bacteria.
      Here we show that light perceived by the LOV domain-regulated two-component
      system (Pst-Lov) of Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) modulates
      virulence against A. thaliana. Bioinformatic analysis and the existence of an
      episomal circular intermediate indicate that the locus encoding Pst-Lov is
      present in an active genomic island acquired by horizontal transfer. Strains
      mutated at Pst-Lov showed enhanced growth on minimal medium and in leaves of A.
      thaliana exposed to light, but not in leaves incubated in darkness or buried in
      the soil. Pst-Lov repressed the expression of principal and alternative sigma
      factor genes and their downstream targets linked to bacterial growth, virulence
      and quorum sensing, in a strictly light-dependent manner. We propose that the
      function of Pst-Lov is to distinguish between soil (dark) and leaf (light)
      environments, attenuating the damage caused to host tissues while releasing
      growth out of the host. Therefore, in addition to its direct actions via
      photosynthesis and plant sensory receptors, light may affect plants indirectly
      via the sensory receptors of bacterial pathogens.

PMID- 23865634
TI  - A method for estimating sex using the clavicle, humerus, radius, and ulna.
AB  - Sex estimation from skeletal remains can be an important part of preliminary
      identification. The best source of information for estimating sex is the pelvis
      but it is not always available for analysis. For these cases, a probabilistic sex
      estimation method is presented using combinations of standard and alternative
      measurements of the clavicle, humerus, radius, and ulna. Various equations are
      developed that are not population specific and that are applicable in various
      recovery scenarios. The equations were tested using four independent samples (n >
      370), including a forensic sample. Allocation accuracies vary by test sample and
      equation and are consistently good (87.4-97.5%) except for a sample of very small
      males that show the extreme effects of poverty and mortality bias. For many of
      the cases where allocation was incorrect, the probabilistic approach indicated
      that no confidence should be placed in the incorrect allocation and the unknown
      should be classified as sex indeterminate.

PMID- 23865635
TI  - Clinical improvement of chromoblastomycosis refractory to itraconazole
      successfully treated with high dose of terbinafine.

PMID- 23865636
TI  - Contingency nature of Helicobacter bizzozeronii oxygen-insensitive NAD(P)H
      nitroreductase (HBZC1_00960) and its role in metronidazole resistance.
AB  - Genomic analysis of a metronidazole resistant H. bizzozeronii strain revealed a
      frame length extension of the oxygen-insensitive NAD(P)H-nitroreductase
      HBZC1_00960 (RdxA), associated with the disruption of the C-terminal cysteine
      containing conserved region (IACLXALGK). This was the result of the extension
      (from C8 to C9) of a simple sequence cytosine repeat (SSCR) located in the 3' of
      the gene. A 3' SSCR is also present in the rdxA homolog of H. heilmannii sensu
      stricto, but not in H. pylori. We showed that in the majority of in vitro
      spontaneous H. bizzozeronii metronidazole resistant mutants, the extension of the
      3' SSCR of rdxA was the only mutation observed. In addition, we observed that H.
      bizzozeronii DeltardxA mutant strain showed the same MIC value of metronidazole
      observed in the spontaneous mutants. These data indicate that loss of function
      mutations in rdxA and in particular the disruption of the conserved region
      IACLXALGK is associated with reduced susceptibility to metronidazole in H.
      bizzozeronii. Slipped-strand mispairing of the SSCR located in the 3' of the H.
      bizzozeronii rdxA appears to be the main mechanism. We also observed that H.
      bizzozeronii acquires resistance to metronidazole at high mutation rate, and that
      serial passages in vitro without selection induced an increased level of
      susceptibility. In conclusion, contrary to what was previously described in H.
      pylori, the H. bizzozeronii rdxA appears to be a contingency gene which undergoes
      phase variation. The contingency nature of rdxA should be carefully considered
      when metronidazole is used in the treatment of H. heilmannii-associated
      gastritis. 

PMID- 23865637
TI  - American and Chinese children's evaluations of personal domain events and
      resistance to parental authority.
AB  - A total of 267 five-, seven-, and ten-year-olds (M = 7.62), 147 in Hong Kong and
      120 in the United States, evaluated hypothetical personal (and moral) events
      described as either essential or peripheral to actors' identity. Except for young
      Chinese in the peripheral condition, straightforward personal events were
      overwhelmingly evaluated as acceptable based on personal justifications. Children
      primarily endorsed compliance, but attributed negative emotions to actors when
      mothers forbade personal choices, especially when described as essential to
      identity. Conventional justifications declined among Chinese children and
      pragmatic justifications for these judgments increased with age for all children,
      as did judgments that personal events were up to the child. Rules were seen as
      more legitimate and events were seen as more up to mothers to decide for moral
      than personal events.

PMID- 23865638
TI  - Selective nitrite reduction at heterobimetallic CoMg complexes.
AB  - Heme-containing nitrite reductases bind and activate nitrite by a mechanism that
      is proposed to involve interactions with Bronsted acidic residues in the
      secondary coordination sphere. To model this functionality using synthetic
      platforms that incorporate a Lewis acidic site, heterobimetallic CoMg complexes
      supported by diimine-dioxime ligands are described. The neutral (MU-NO2)CoMg
      species 3 is synthesized from the [(MU-OAc)(Br)CoMg](+) complex 1 by a sequence
      of one-electron reduction and ligand substitution reactions. Data are presented
      for a redox series of nitrite adducts, featuring a conserved MU-(eta(1)-N:eta(1)
      O)-NO2 motif, derived from this synthon. Conditions are identified for the proton
      induced N-O bond heterolysis of bound NO2(-) in the most reduced member of this
      series, affording the [(NO)(Cl)CoMg(H2O)](+) complex 6. Reduction of this complex
      followed by protonation leads to the evolution of free N2O. On the basis of these
      stoichiometric reactivity studies, the competence of complex 1 as a NO2(-)
      reduction catalyst is evaluated using electrochemical methods. In bulk
      electrolysis experiments, conducted at -1.2 V vs SCE using Et3NHCl as a proton
      source, N2O is produced selectively without the competing formation of NH3,
      NH2OH, or H2. 

PMID- 23865640
TI  - Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer's
      disease: an early event in disease pathogenesis.
AB  - To explore the hypothesis that alterations in cellular membrane lipids are
      present at the stage of pre-clinical Alzheimer's disease (AD) (i.e., cognitively
      normal at death, but with AD neuropathology), we performed targeted shotgun
      lipidomics of lipid extracts from post-mortem brains of subjects with pre
      clinical AD. We found sulfatide levels were significantly lower in subjects with
      pre-clinical AD compared to those without AD neuropathology. We also found that
      the level of ethanolamine glycerophospholipid was marginally lower at this stage
      of AD, whereas changes of the ceramide levels were undetectable with the
      available samples. These results indicate that cellular membrane defects are
      present at the earliest stages of AD pathogenesis and also suggest that sulfatide
      loss is among the earliest events of AD development, while alterations in the
      levels of ethanolamine glycerophospholipid and ceramide occur relatively later in
      disease. 

PMID- 23865641
TI  - Cyanidiales diversity in Yellowstone National Park.
AB  - The Cyanidiales are unicellular red algae that are unique among phototrophs. They
      thrive in acidic, moderately high-temperature habitats typically associated with
      geothermally active regions, although much remains to be learned about their
      distribution and diversity within such extreme environments. We focused on
      Yellowstone National Park (YNP), using culture-dependent efforts in combination
      with a park-wide environmental polymerase chain reaction (PCR) survey to examine
      Cyanidiales diversity and distribution in aqueous (i.e. submerged), soil and
      endolithic environments. Phylogenetic reconstruction of Cyanidiales biodiversity
      demonstrated the presence of Cyanidioschyzon and Galdieria lineages exhibiting
      distinct habitat preferences. Cyanidioschyzon was the only phylotype detected in
      aqueous environments, but was also prominent in moist soil and endolithic
      habitats, environments where this genus was thought to be scarce. Galdieria was
      found in soil and endolithic samples, but absent in aqueous habitats.
      Interestingly, Cyanidium could not be found in the surveys, suggesting this genus
      may be absent or rare in YNP. Direct microscopic counts and viable counts from
      soil samples collected along a moisture gradient were positively correlated with
      moisture content, providing the first in situ evidence that gravimetric moisture
      is an important environmental parameter controlling distribution of these algae.

PMID- 23865639
TI  - Tissue-engineered mandibular bone reconstruction for continuity defects: a
      systematic approach to the literature.
AB  - BACKGROUND: Despite significant surgical advances over the last decades,
      segmental mandibular bone repair remains a challenge. In light of this, tissue
      engineering might offer a next step in the evolution of mandibular
      reconstruction. PURPOSE: The purpose of the present report was to (1)
      systematically review preclinical in vivo as well as clinical literature
      regarding bone tissue engineering for mandibular continuity defects, and (2) to
      analyze their effectiveness. MATERIALS AND METHODS: An electronic search in the
      databases of the National Library of Medicine and ISI Web of Knowledge was
      carried out. Only publications in English were considered, and the search was
      broadened to animals and humans. Furthermore, the reference lists of related
      review articles and publications selected for inclusion in this review were
      systematically screened. Results of histology data and amount of bone bridging
      were chosen as primary outcome variables. However, for human reports, clinical
      radiographic evidence was accepted for defined primary outcome variable. The
      biomechanical properties, scaffold degradation, and clinical wound healing were
      selected as co-outcome variables. RESULTS: The electronic search in the databases
      of the National Library of Medicine and ISI Web of Knowledge resulted in the
      identification of 6727 and 5017 titles, respectively. Thereafter, title
      assessment and hand search resulted in 128 abstracts, 101 full-text articles, and
      29 scientific papers reporting on animal experiments as well as 11 papers
      presenting human data on the subject of tissue-engineered reconstruction of
      mandibular continuity defects that could be included in the present review.
      CONCLUSIONS: It was concluded that (1) published preclinical in vivo as well as
      clinical data are limited, and (2) tissue-engineered approaches demonstrate some
      clinical potential as an alternative to autogenous bone grafting.

PMID- 23865642
TI  - Morphology, morphogenesis, and molecular phylogeny of Anteholosticha multicirrata
      n. sp. (Ciliophora, Spirotrichea) with a note on morphogenesis of A. pulchra
      (Kahl, 1932) Berger, 2003.
AB  - Two marine urostylid ciliates, Anteholosticha multicirrata n. sp. and
      Anteholosticha pulchra (Kahl, 1932) Berger, 2003, were collected from South
      Korea. These species were identified based on morphology, morphogenesis, and SSU
      rRNA gene sequence comparison. Anteholosticha multicirrata n. sp. is
      characterized by the following features: body size 90-125 * 30-45 MUm in vivo,
      shape slender to ellipsoidal in outline, with yellow-greenish cortical granules
      distributed along and between dorsal kineties and cirri; single contractile
      vacuole positioned on left at mid-body; three frontal, five to seven
      frontoterminal, one buccal, one to two pretransverse and four to six transverse
      cirri; three complete dorsal kineties; one left and one right marginal cirral
      row; about 117 macronuclear nodules; and three to four micronuclei observed
      during morphogenesis. In addition, based on the observations of morphogenesis, we
      found that A. pulchra has pretransverse cirri, which were not described in detail
      in previous studies. Nuclear small subunit ribosomal RNA (SSU rRNA) gene was used
      to analyse their phylogenetic relationship, and the gene tree supports that the
      genus Anteholosticha is a highly polyphyletic group. 

PMID- 23865643
TI  - A two-dimensional model for stress driven diffusion in bone tissue.
AB  - The growth and resorption of bone are governed by interaction between several
      cells such as bone-forming osteoblasts, osteocytes, lining cells and bone
      resorbing osteoclasts. The cells considered in this study reside in the
      periosteum. Furthermore, they are believed to be activated by certain substances
      to initiate bone growth. This study focuses on the role that stress driven
      diffusion plays in the transport of these substances from the medullary cavity to
      the periosteum. Calculations of stress driven diffusion are performed under
      steady state conditions using a finite element method with the concentration of
      nutrients in the cambium layer of the periosteum obtained for different choices
      of load frequencies. The results are compared with experimental findings,
      suggesting that increased bone growth occurs in the neighbourhood of relatively
      high nutrient concentration. 

PMID- 23865644
TI  - Randomized, community-based pharmacy intervention to expand services beyond sale
      of sterile syringes to injection drug users in pharmacies in New York City.
AB  - Structural interventions may help reduce racial/ethnic disparities in HIV. In
      2009 to 2011, we randomized pharmacies participating in a nonprescription syringe
      access program in minority communities to intervention (pharmacy enrolled and
      delivered HIV risk reduction information to injection drug users [IDUs]), primary
      control (pharmacy only enrolled IDUs), and secondary control (pharmacy did not
      engage IDUs). Intervention pharmacy staff reported more support for syringe sales
      than did control staff. An expanded pharmacy role in HIV risk reduction may be
      helpful. 

PMID- 23865645
TI  - Overcoming the taboo: advancing the global agenda for menstrual hygiene
      management for schoolgirls.

PMID- 23865646
TI  - Electronic health records and US public health: current realities and future
      promise.
AB  - Electronic health records (EHRs) could contribute to improving population health
      in the United States. Realizing this potential will require understanding what
      EHRs can realistically offer to efforts to improve population health, the
      requirements for obtaining useful information from EHRs, and a plan for
      addressing these requirements. Potential contributions of EHRs to improving
      population health include better understanding of the level and distribution of
      disease, function, and well-being within populations. Requirements are improved
      population coverage of EHRs, standardized EHR content and reporting methods, and
      adequate legal authority for using EHRs, particularly for population health. A
      collaborative national effort to address the most pressing prerequisites for and
      barriers to the use of EHRs for improving population health is needed to realize
      the EHR's potential. 

PMID- 23865647
TI  - Reducing risk behaviors linked to noncommunicable diseases in Mongolia: a
      randomized controlled trial.
AB  - OBJECTIVES: We tested the efficacy of a 6-session, evidence-based health
      promotion intervention aimed at reducing noncommunicable disease (NCD) risk
      behaviors. METHODS: Two hundred male and female factory workers in Ulaanbaatar,
      Mongolia were randomly assigned to groups receiving either the health promotion
      intervention or a time-matched financial literacy control intervention. RESULTS:
      The health promotion intervention increased daily fruit and vegetable intake and
      physical activity, increased readiness for NCD risk behavior reduction and health
      promotion knowledge, and reduced the number of daily alcoholic drinks and
      diabetes symptoms 3 months after the intervention. CONCLUSIONS: The findings
      support the efficacy of the intervention to reduce risk behaviors associated with
      NCDs. Dissemination of the intervention may improve productivity, reduce costs of
      health services, and better the quality of life for Mongolians.

PMID- 23865648
TI  - The "path" not taken: exploring structural differences in mapped- versus shortest
      network-path school travel routes.
AB  - OBJECTIVES: School route measurement often involves estimating the shortest
      network path. We challenged the relatively uncritical adoption of this method in
      school travel research and tested the route discordance hypothesis that several
      types of difference exist between shortest network paths and reported school
      routes. METHODS: We constructed the mapped and shortest path through network
      routes for a sample of 759 children aged 9 to 13 years in grades 5 and 6 (boys =
      45%, girls = 54%, unreported gender = 1%), in Toronto, Ontario, Canada. We used
      Wilcoxon signed-rank tests to compare reported with shortest-path route measures
      including distance, route directness, intersection crossings, and route overlap.
      Measurement difference was explored by mode and location. RESULTS: We found
      statistical evidence of route discordance for walkers and children who were
      driven and detected it more often for inner suburban cases. Evidence of route
      discordance varied by mode and school location. CONCLUSIONS: We found
      statistically significant differences for route structure and built environment
      variables measured along reported and geographic information systems-based
      shortest-path school routes. Uncertainty produced by the shortest-path approach
      challenges its conceptual and empirical validity in school travel research.

PMID- 23865649
TI  - Weight status of Mexican immigrant women: a comparison with women in Mexico and
      with US-born Mexican American women.
AB  - OBJECTIVES: We assessed the association between birthplace, residence, or years
      in the United States and actual weight (body mass index), perceived weight
      accuracy, or provider screens for overweight or obesity among Mexican immigrant
      women. METHODS: We used linked data from Health and Nutrition Examination Survey
      waves 2001-2006 and 2006 National Mexican Health and Nutrition Survey to compare
      513 immigrants with 9527 women in Mexico and 342 US-born Mexican American women.
      RESULTS: Immigrants were more likely than women in Mexico to be obese and to
      perceive themselves as overweight or obese after adjustment for confounders.
      Recent immigrants had similar weight-related outcomes as women in Mexico.
      Immigrants were less likely to be obese than were US-born Mexican Americans.
      Within the overweight or obese population, reported provider screens were higher
      among immigrants than among women in Mexico, but lower than among US-born Mexican
      Americans. US residency of at least 5 years but less than 20 years and reporting
      insufficient provider screens elevated obesity risk. CONCLUSIONS: Mexican-origin
      women in the United States and Mexico are at risk for overweight and obesity. We
      found no evidence of a "healthy immigrant" effect.

PMID- 23865650
TI  - Oral health care for children in countries using dental therapists in public,
      school-based programs, contrasted with that of the United States, using dentists
      in a private practice model.
AB  - The United States faces a significant problem with access to oral health care,
      particularly for children. More than 50 countries have developed an alternative
      dental provider, a dental therapist, practicing in public, school-based programs,
      to address children's access to care. This delivery model has been demonstrated
      to improve access to care and oral health outcomes while providing quality care
      economically. We summarize elements of a recent major review of the global
      literature on the use of dental therapists, "A Review of the Global Literature on
      Dental Therapists: In the Context of the Movement to Add Dental Therapists to the
      Oral Health Workforce in the United States." We contrast the success of a school
      based model of caring for children by dental therapists with that of the US model
      of dentists providing care for children in private practices. 

PMID- 23865651
TI  - Longitudinal associations between types of childhood trauma and suicidal behavior
      among substance users: a cohort study.
AB  - OBJECTIVES: We examined the longitudinal associations between different types and
      severities of childhood trauma and suicide attempts among illicit drug users.
      METHODS: Data came from 2 prospective cohort studies of illicit drug users in
      Vancouver, Canada, in 2005 to 2010. We used recurrent event proportional means
      models to estimate adjusted and weighted associations between types and
      severities of childhood maltreatment and suicide attempts. RESULTS: Of 1634
      participants, 411 (25.2%) reported a history of suicidal behavior at baseline.
      Over 5 years, 80 (4.9%) participants reported 97 suicide attempts, a rate of 2.6
      per 100 person-years. Severe to extreme levels of sexual abuse (adjusted hazard
      ratio [AHR] = 2.5; 95% confidence interval [CI] = 1.4, 4.4), physical abuse (AHR
      = 2.0; 95% CI = 1.1, 3.8), and emotional abuse (AHR = 3.5; 95% CI = 1.4, 8.7)
      predicted suicide attempts. Severe forms of physical and emotional neglect were
      not significantly associated with an increased risk of suicidal behavior.
      CONCLUSIONS: Severe sexual, physical, and emotional childhood abuse confer
      substantial risk of repeated suicidal behavior in adulthood. Illicit drug users
      require intensive secondary suicide prevention efforts, particularly among those
      with a history of childhood trauma.

PMID- 23865652
TI  - Acute alcohol consumption as a contributing factor to suicidal behavior.

PMID- 23865653
TI  - Missed opportunities for improving nutrition through institutional food: the case
      for food worker training.
AB  - The institutional food sector-including food served in schools, child care
      settings, hospitals, and senior centers-is a largely untapped resource for public
      health that may help to arrest increasing rates of obesity and diet-related
      health problems. To make this case, we estimated the reach of a diverse
      institutional food sector in 1 large municipality, New York City, in 2012, and
      explored the potential for improving institutional food by building the skills
      and nutritional knowledge of foodservice workers through training. Drawing on the
      research literature and preliminary data collected in New York City, we discuss
      the dynamics of nutritional decision-making in these settings. Finally, we
      identify opportunities and challenges associated with training the institutional
      food workforce to enhance nutrition and health. 

PMID- 23865654
TI  - The mortality toll of estrogen avoidance: an analysis of excess deaths among
      hysterectomized women aged 50 to 59 years.
AB  - OBJECTIVES: We examined the effect of estrogen avoidance on mortality rates among
      hysterectomized women aged 50 to 59 years. METHODS: We derived a formula to
      relate the excess mortality among hysterectomized women aged 50 to 59 years
      assigned to placebo in the Women's Health Initiative randomized controlled trial
      to the entire population of comparable women in the United States, incorporating
      the decline in estrogen use observed between 2002 and 2011. RESULTS: Over a 10
      year span, starting in 2002, a minimum of 18 601 and as many as 91 610
      postmenopausal women died prematurely because of the avoidance of estrogen
      therapy (ET). CONCLUSIONS: ET in younger postmenopausal women is associated with
      a decisive reduction in all-cause mortality, but estrogen use in this population
      is low and continuing to fall. Our data indicate an associated annual mortality
      toll in the thousands of women aged 50 to 59 years. Informed discussion between
      these women and their health care providers about the effects of ET is a matter
      of considerable urgency.

PMID- 23865655
TI  - Asthma disparities and within-group differences in a national, probability sample
      of same-sex partnered adults.
AB  - OBJECTIVES: We examined the prevalence and correlates of self-reported lifetime
      diagnosis of asthma and current asthma among same-sex and opposite-sex partnered
      adults. METHODS: Data were from the 2004 Behavioral Risk Factor Surveillance
      System, in which same-sex partnership was a response option to a family planning
      item in the core questionnaire. Self-reported lifetime diagnosis of asthma and
      current asthma were examined in logistic regression models adjusted for
      demographic characteristics and asthma-related confounding factors and stratified
      by both gender and same-sex partnership status. RESULTS: Significantly higher
      proportions of same-sex partnered male and female respondents reported lifetime
      and current asthma compared with their opposite-sex partnered peers. In adjusted
      analyses, same-sex partnership status remained significantly associated with
      asthma outcomes among men and women, with odds ratios ranging from 1.57 to 2.34.
      CONCLUSIONS: Results corroborated past studies that indicated asthma
      disproportionately affects sexual minority populations. The addition of sexual
      minority status questions to federal survey projects is key to further exploring
      health disparities in this population. Future studies are needed to investigate
      the etiology of this disparity.

PMID- 23865656
TI  - Psychological first aid: a consensus-derived, empirically supported, competency
      based training model.
AB  - Surges in demand for professional mental health services occasioned by disasters
      represent a major public health challenge. To build response capacity, numerous
      psychological first aid (PFA) training models for professional and lay audiences
      have been developed that, although often concurring on broad intervention aims,
      have not systematically addressed pedagogical elements necessary for optimal
      learning or teaching. We describe a competency-based model of PFA training
      developed under the auspices of the Centers for Disease Control and Prevention
      and the Association of Schools of Public Health. We explain the approach used for
      developing and refining the competency set and summarize the observable
      knowledge, skills, and attitudes underlying the 6 core competency domains. We
      discuss the strategies for model dissemination, validation, and adoption in
      professional and lay communities.

PMID- 23865657
TI  - Supplementing menu labeling with calorie recommendations to test for facilitation
      effects.
AB  - OBJECTIVES: We examined the effect on food purchases of adding recommended
      calorie intake per day or per meal to the mandated calorie information posted on
      chain restaurant menus. METHODS: Before and after New York City implemented
      calorie posting on chain restaurant menus in 2008, we provided daily, per-meal,
      or no calorie recommendations to randomized subsets of adult lunchtime customers
      (n = 1121) entering 2 McDonald's restaurants, in Manhattan and Brooklyn, and
      collected receipts and survey responses as they exited. In linear and logistic
      regressions, with adjustment for gender, race, age, and day, we tested for simple
      differences in calories consumed and interactions between variables. RESULTS:
      Posting calorie benchmarks had no direct impact, nor did it moderate the impact
      of calorie labels on food purchases. The recommendation appeared to promote a
      slight increase in calorie intake, attributable to increased purchases of higher
      calorie entrees. CONCLUSIONS: These results do not support the introduction of
      calorie recommendations as a means of enhancing the impact of posted calorie
      information or reducing the contribution of restaurant dining to the obesity
      epidemic.

PMID- 23865658
TI  - Uptake and predictors of anal cancer screening in men who have sex with men.
AB  - OBJECTIVES: We investigated attitudes about and acceptance of anal Papanicolaou
      (Pap) screening among men who have sex with men (MSM). METHODS: Free anal Pap
      screening (cytology) was offered to 1742 MSM in the Multicenter AIDS Cohort
      Study, who reported history of, attitudes about, and experience with screening.
      We explored predictors of declining screening with multivariate logistic
      regression. RESULTS: A history of anal Pap screening was uncommon among non-HIV
      infected MSM, but more common among HIV-infected MSM (10% vs 39%; P < .001). Most
      participants expressed moderate or strong interest in screening (86%), no anxiety
      about screening (66%), and a strong belief in the utility of screening (65%).
      Acceptance of screening during this study was high (85%) across all 4 US sites.
      Among those screened, most reported it was "not a big deal" or "not as bad as
      expected," and 3% reported that it was "scary." Declining to have screening was
      associated with Black race, anxiety about screening, and low interest, but not
      age or HIV status. CONCLUSIONS: This study demonstrated high acceptance of anal
      Pap screening among both HIV-infected and non-HIV-infected MSM across 4 US sites.

PMID- 23865659
TI  - Designing for dissemination among public health researchers: findings from a
      national survey in the United States.
AB  - OBJECTIVES: We have described the practice of designing for dissemination among
      researchers in the United States with the intent of identifying gaps and areas
      for improvement. METHODS: In 2012, we conducted a cross-sectional study of 266
      researchers using a search of the top 12 public health journals in PubMed and
      lists available from government-sponsored research. The sample involved
      scientists at universities, the National Institutes of Health, and the Centers
      for Disease Control and Prevention in the United States. RESULTS: In the pooled
      sample, 73% of respondents estimated they spent less than 10% of their time on
      dissemination. About half of respondents (53%) had a person or team in their unit
      dedicated to dissemination. Seventeen percent of all respondents used a framework
      or theory to plan their dissemination activities. One third of respondents (34%)
      always or usually involved stakeholders in the research process. CONCLUSIONS: The
      current data and the existing literature suggest considerable room for
      improvement in designing for dissemination.

PMID- 23865660
TI  - Social media adoption in local health departments nationwide.
AB  - OBJECTIVES: We examined whether characteristics of local health departments (LHD)
      and their geographic region were associated with using Facebook and Twitter. We
      also examined the number of tweets per month for Twitter accounts as an indicator
      of social media use by LHDs. METHODS: In 2012, we searched for Facebook and
      Twitter accounts for 2565 LHDs nationwide, and collected adoption date and number
      of connections for each account. Number of tweets sent indicated LHD use of
      social media. LHDs were classified as innovators, early adopters, or nonadopters.
      Characteristics of LHDs were compared across adoption categories, and we examined
      geographic characteristics, connections, and use. RESULTS: Twenty-four percent of
      LHDs had Facebook, 8% had Twitter, and 7% had both. LHDs serving larger
      populations were more likely to be innovators, tweeted more often, and had more
      social media connections. Frequency of tweeting was not associated with adoption
      category. There were differences in adoption across geographic regions, with
      western states more likely to be innovators. Innovation was also higher in states
      where the state health department adopted social media. CONCLUSIONS: Social media
      has the potential to aid LHDs in disseminating information across the public
      health system. More evidence is needed to develop best practices for this
      emerging tool.

PMID- 23865661
TI  - Smokers with behavioral health comorbidity should be designated a tobacco use
      disparity group.
AB  - Smokers with co-occurring mental illness or substance use disorders are not
      designated a disparity group or priority population by most national public
      health and tobacco control groups. These smokers fulfill the criteria commonly
      used to identify groups that merit special attention: targeted marketing by the
      tobacco industry, high smoking prevalence rates, heavy economic and health
      burdens from tobacco, limited access to treatment, and longer durations of
      smoking with less cessation. A national effort to increase surveillance,
      research, and treatment is needed. Designating smokers with behavioral health
      comorbidity a priority group will bring much-needed attention and resources. The
      disparity in smoking rates among persons with behavioral health issues relative
      to the general population will worsen over time if their needs remain
      unaddressed. 

PMID- 23865662
TI  - The association between client characteristics and recovery in California's
      comprehensive community mental health programs.
AB  - OBJECTIVES: In November 2004, California voters passed the Mental Health Services
      Act, which allocated more than $3 billion for comprehensive community mental
      health programs. We examined whether these county-level programs, known as "full
      service partnerships," promoted independent living arrangements (i.e., recovery)
      among their clients. METHODS: We used Markov chain models to identify
      probabilities of residential transitions among 8 living arrangements (n = 9208
      adults followed up to 4 years). We modeled these transitions on the basis of
      patterns of program participation and clinical and sociodemographic
      characteristics. RESULTS: Interrupted program participation and substance abuse
      were significantly associated with a reduced likelihood of independent living and
      a greater probability of homelessness and incarceration. Persons with
      schizophrenia were the least likely to live independently, followed by persons
      with bipolar disorder. Compared with Whites, non-Whites were more frequently
      found to be homeless or in jail. CONCLUSIONS: Clients with sustained enrollment
      in California's comprehensive community mental health programs appear most likely
      to transition to independent living. The likelihood of this transition, however,
      shows a disparity in that ethnic minority clients appear least likely to
      transition to independent living.

PMID- 23865663
TI  - Spanish-language community-based mental health treatment programs, policy
      required language-assistance programming, and mental health treatment access
      among Spanish-speaking clients.
AB  - OBJECTIVES: We investigated the extent to which implementing language assistance
      programming through contracting with community-based organizations improved the
      accessibility of mental health care under Medi-Cal (California's Medicaid
      program) for Spanish-speaking persons with limited English proficiency, and
      whether it reduced language-based treatment access disparities. METHODS: Using a
      time series nonequivalent control group design, we studied county-level
      penetration of language assistance programming over 10 years (1997-2006) for
      Spanish-speaking persons with limited English proficiency covered under Medi-Cal.
      We used linear regression with county fixed effects to control for ongoing trends
      and other influences. RESULTS: When county mental health plans contracted with
      community-based organizations, those implementing language assistance programming
      increased penetration rates of Spanish-language mental health services under Medi
      Cal more than other plans (0.28 percentage points, a 25% increase on average; P <
      .05). However, the increase was insufficient to significantly reduce language
      related disparities. CONCLUSIONS: Mental health treatment programs operated by
      community-based organizations may have moderately improved access after
      implementing required language assistance programming, but the programming did
      not reduce entrenched disparities in the accessibility of mental health services.

PMID- 23865664
TI  - A cross-national study on prevalence of mental disorders, service use, and
      adequacy of treatment among Mexican and Mexican American populations.
AB  - OBJECTIVES: We examined differences in the use of mental health services,
      conditional on the presence of psychiatric disorders, across groups of Mexico's
      population with different US migration exposure and in successive generations of
      Mexican Americans in the United States. METHODS: We merged surveys conducted in
      Mexico (Mexican National Comorbidity Survey, 2001-2002) and the United States
      (Collaborative Psychiatric Epidemiology Surveys, 2001-2003). We compared
      psychiatric disorders and mental health service use, assessed in both countries
      with the Composite International Diagnostic Interview, across migration groups.
      RESULTS: The 12-month prevalence of any disorder was more than twice as high
      among third- and higher generation Mexican Americans (21%) than among Mexicans
      with no migrant in their family (8%). Among people with a disorder, the odds of
      receiving any mental health service were higher in the latter group relative to
      the former (odds ratio = 3.35; 95% confidence interval = 1.82, 6.17) but the age-
      and gender-adjusted prevalence of untreated disorder was also higher.
      CONCLUSIONS: Advancing understanding of the specific enabling and dispositional
      factors that result in increases in mental health care may contribute to reducing
      service use disparities across ethnic groups in the United States.

PMID- 23865665
TI  - The National Prevention Strategy and breast cancer screening: scientific evidence
      for public health action.
AB  - Mammography screening rates in the United States have remained fairly stable over
      the past decade, and screening rates remain low for some groups. We examined
      insights from recent public health research on breast cancer screening to
      identify promising new approaches to improve screening rates and address
      persistent health disparities in mammography use. We considered this research in
      the context of the four strategic directions of the National Prevention Strategy:
      elimination of health disparities, empowered people, healthy and safe community
      environments, and clinical and community preventive services. This research
      points to the value of direct outreach and case management services,
      interventions to support more patient-centered models of care, and more
      organized, population-based approaches to identify women who are eligible to be
      screened, encourage participation, and monitor results. 

PMID- 23865666
TI  - Lifetime socioeconomic inequalities in physical and cognitive aging.
AB  - OBJECTIVES: We examined the relationship between childhood and adult
      socioeconomic position (SEP) and objectively assessed, later-life functioning.
      METHODS: We used the Medical Research Council's National Survey of Health and
      Development data to examine performance at 60 to 64 years (obtained in 2006-2011)
      for a representative UK sample. We compared 9 physical and cognitive performance
      measures (forced expiratory volume, forced vital capacity, handgrip strength,
      chair rise time, standing balance time, timed get up and go speed, verbal memory
      score, processing speed, and simple reaction time) over the SEP distribution.
      RESULTS: Each performance measure was socially graded. Those at the top of the
      childhood SEP distribution had between 7% and 20% better performance than those
      at the bottom. Inequalities generally persisted after adjustment for adult SEP.
      When we combined the 9 performance measures, the relative difference was 66% (95%
      confidence interval = 53%, 78%). CONCLUSIONS: Public health practice should
      monitor and target inequalities in functional performance, as well as risk of
      disease and death. Effective strategies will need to affect the social
      determinants of health in early life to influence inequalities into old age.

PMID- 23865667
TI  - Migration circumstances, psychological distress, and self-rated physical health
      for Latino immigrants in the United States.
AB  - OBJECTIVES: We determined the impact of premigration circumstances on
      postmigration psychological distress and self-rated physical health among Latino
      immigrants. METHODS: We estimated ordinary least squares and logistic regression
      models for Latino immigrants in the 2002-2003 National Latino and Asian American
      Study (n = 1603). RESULTS: Mean psychological distress scores (range = 10-50)
      were 14.8 for women and 12.7 for men; 35% of women and 27% of men reported fair
      or poor physical health. A third of the sample reported having to migrate; up to
      46% reported unplanned migration. In multivariate analyses, immigration-related
      stress was significantly associated with psychological distress, but not with
      self-rated health, for both Latino men and women. Having to migrate was
      associated with increased psychological distress for Puerto Rican and Cuban women
      respondents and with poorer physical health for Puerto Rican migrant men.
      Unplanned migration was significantly associated with poorer physical health for
      all Latina women respondents. CONCLUSIONS: The context of both pre- and
      postmigration has an impact on immigrant health. Those involved in public health
      research, policy, and practice should consider variation in immigrant health by
      migration circumstances, including the context of exit and other immigration
      related stressors.

PMID- 23865668
TI  - Trends of edentulism among middle-aged and older Asian Americans.
AB  - OBJECTIVES: We estimated national trends of the prevalence of edentulism
      (complete tooth loss) for Asian American subgroups in the United States and
      investigated factors that could contribute to improvements in edentulism across
      populations over time. METHODS: We used 10 waves of the National Health Interview
      Survey data collected from 1999 to 2008. Eligible respondents were those aged 50
      years and older who completed the question on tooth loss. We contrasted the odds
      and probabilities of edentulism over time in Chinese, Filipinos, Asian Indians,
      and other Asians with those in Whites, Blacks, and Hispanics. RESULTS: The rates
      of edentulism differed substantially across Asian subgroups. Compared with
      Whites, Chinese and other Asians had a lower risk of being edentulous, whereas
      being Filipino increased the odds. The rate for Asian Indians was similar to that
      for Whites. Nonetheless, rates of decline were similar across the Asian
      population groups. CONCLUSIONS: Asian Americans are heterogeneous in edentulism.
      Innovative and sustainable public health programs and services are essential to
      prevent oral health diseases and conditions.

PMID- 23865669
TI  - Medicaid family planning expansions and related preventive care.
AB  - I examined the impact of state expansions in eligibility for Medicaid family
      planning services on the utilization of Papanicolaou (Pap) tests, clinical breast
      examinations, HIV testing, and routine doctor check-ups among women aged 21 to 44
      years using the Behavioral Risk Factor Surveillance System (1993-2009). Using a
      natural experiment approach, I found significant increases in Pap tests and
      clinical breast examinations among women eligible for services under the
      expansions but no significant change in HIV testing or routine doctor check-ups. 

PMID- 23865670
TI  - Considering the complexity in HIV/AIDS and the environment.

PMID- 23865671
TI  - Haemophilia in extreme immature preterm infants: increased risk for intracranial
      haemorrhage?
AB  - Haemophiliacs and extremely premature infants are both at an increased risk for
      intracranial haemorrhage; both conditions might be further elevating the risk. We
      report a case of a very immature preterm-infant of 26 gestational weeks (birth
      weight 635 g) with severe haemophilia A. Furthermore, we provide an overview of
      the published literature on this subject matter. Until now, deficiency of factor
      VIII or IX as a potential risk factor for ICH in preterm infants remains
      controversial. However, prophylactic substitution of factor VIII or IX in preterm
      infants with haemophilia may minimize the risk of bleeding complications and
      neurologic sequelae.

PMID- 23865672
TI  - Macroporous graphene oxide-polymer composite prepared through pickering high
      internal phase emulsions.
AB  - Macroporous polymer-graphene oxide (GO) composites were successfully prepared
      using Pickering high internal phase emulsion (HIPE) templates. GO flakes were
      modified by the cationic surfactant cetyltrimethylammonium bromide (CTAB) and
      used as the stabilizer of water-in-oil (W/O) Pickering emulsions. CTAB-modified
      GO is effective at stabilizing W/O Pickering HIPEs, and the lowest GO content is
      only about 0.2 mg mL(-1) (relative to the volume of the oil phase). The close
      cell morphology of the resulting poly-Pickering HIPEs is observed, and the void
      size of the porous polymers is tuned by varying the concentration of GO. Three
      dimensional macroporous chemically modified graphene (CMG) monoliths with a high
      specific surface area of about 490 m(2) g(-1) were obtained after removing the
      cellular polymer substrates through calcination. The micropores were also found
      in CMGs, which may be caused by the decomposition of CTAB adsorbed on the surface
      of GO. 

PMID- 23865673
TI  - Unexpected random urinary protein:creatinine ratio results-limitations of the
      pyrocatechol violet-dye method.
AB  - BACKGROUND: For clinicians, it is important to rely on accurate laboratory
      results for patient care and optimal use of health care resources. We sought to
      explore our observations that urine protein:creatinine ratios (PrCr) >=30 mg/mmol
      are seen not infrequently associated with normal pregnancy outcome. METHODS:
      Urine samples were collected prospectively from 160 pregnant women attending high
      risk maternity clinics at a tertiary care facility. Urinary protein was measured
      using a pyrocatechol violet assay and urinary creatinine by an enzymatic method
      on Vitros analysers. Maternal/perinatal outcomes were abstracted from hospital
      records. RESULTS: 91/233 (39.1%) samples had a PrCr >=30 mg/mmol, especially when
      urinary creatinine concentration was <3 mM (94.1%) vs. >=3 mM (16.4%) (p <
      0.001). When using the last sample before delivery, 47/160 (29.4%) had a PrCr
      >=30 mg/mmol in diluted urine vs. only 17/160 (15.4%) in more concentrated urine
      (p < 0.001); PrCr positive results were also more frequent among the 32 (20.0%)
      women with known normal pregnancy outcome (90.9% vs. 0) (p < 0.001). Using the
      same analyser, 0.12 g/L urinary protein was 'detected' in deionised water. Re
      analysis of data from two cohorts revealed substantially less inflation of PrCr
      in dilute urine using a pyrogallol red assay. CONCLUSIONS: Random urinary PrCr
      was overestimated in dilute urine when tested using a common pyrocatechol violet
      dye-based method. This effect was reduced in cohorts when pyrogallol red assays
      were used. False positive results can impact on diagnosis and patient care. This
      highlights the need for both clinical and laboratory quality improvement projects
      and standardization of laboratory protein measurement.

PMID- 23865675
TI  - Relationship between muscle mass and muscle strength, and the impact of
      comorbidities: a population-based, cross-sectional study of older adults in the
      United States.
AB  - BACKGROUND: Loss of muscle mass and muscle strength are natural consequences of
      the aging process, accompanied by an increased prevalence of chronic health
      conditions. Research suggests that in the elderly, the presence of comorbidities
      may impact the muscle mass/strength relationship. The objectives of this study
      were to characterize the muscle mass/strength relationship in older adults in the
      USA and to examine the impact of a variety of comorbidities on this relationship.
      METHODS: Data were obtained from the National Health and Nutrition Examination
      Survey 1999-2002 databases. Subjects aged 50 years and older were included in the
      present study. Muscle mass was assessed by height-adjusted appendicular skeleton
      muscle mass (aASM) in kg/m2, as measured by dual-energy x-ray absorptiometry.
      Muscle strength was assessed via isokinetic quadriceps strength (IQS) in newton
      as measured by a dynamometer. The relationship between aASM and IQS was assessed
      adjusting for age and gender. The effects of a variety of comorbidities on IQS
      and/or on the relationship between IQS and aASM were assessed using multiple
      regression models. RESULTS: This study included 2,647 individuals, with a mean
      age of 62.6 years and 52.9% of whom were female. The mean (SE) aASM (kg/m2) was
      7.3 (0.04), and the mean (SE) IQS (newton) was 365.0 (3.00). After adjusting for
      age and gender, the correlation coefficient between aASM and IQS was 0.365 (P <
      0.001). Diabetes, coronary heart disease/congestive heart failure (CHD/CHF), and
      vision problems were significant predictors of lower muscle strength (P < 0.05)
      in the multiple regression models that adjusted for age, gender, and aASM, and
      obesity significantly modified the relationship between aASM and IQS (P < 0.05).
      CONCLUSIONS: Among individuals aged 50 and older in the US, muscle mass and
      muscle strength are positively correlated, independent of the associations of age
      and gender with muscle mass and strength. A variety of comorbid medical
      conditions serve as independent predictors of lower muscle strength (e.g.,
      diabetes, CHD/CHF, vision problems) and/or modify the relationship between muscle
      mass and muscle strength (e.g., obesity).

PMID- 23865676
TI  - A reductant-resistant and metal-free fluorescent probe for nitroxyl applicable to
      living cells.
AB  - Nitroxyl (HNO) is a one-electron reduced and protonated derivative of nitric
      oxide (NO) and has characteristic biological and pharmacological effects distinct
      from those of NO. However, studies of its biosynthesis and activities are
      restricted by the lack of versatile HNO detection methods applicable to living
      cells. Here, we report the first metal-free and reductant-resistant HNO imaging
      probe available for use in living cells, P-Rhod. It consists of a rhodol
      derivative moiety as the fluorophore, linked via an ester moiety to a
      diphenylphosphinobenzoyl group, which forms an aza-ylide upon reaction with HNO.
      Intramolecular attack of the aza-ylide on the ester carbonyl group releases a
      fluorescent rhodol derivative. P-Rhod showed high selectivity for HNO in the
      presence of various biologically relevant reductants, such as glutathione and
      ascorbate, in comparison with previous HNO probes. We show that P-Rhod can detect
      not only HNO enzymatically generated in the horseradish peroxidase-hydroxylamine
      system in vitro but also intracellular HNO release from Angeli's salt in living
      cells. These results suggest that P-Rhod is suitable for detection of HNO in
      living cells. 

PMID- 23865674
TI  - Transcriptome analyses of the human retina identify unprecedented transcript
      diversity and 3.5 Mb of novel transcribed sequence via significant alternative
      splicing and novel genes.
AB  - BACKGROUND: The retina is a complex tissue comprised of multiple cell types that
      is affected by a diverse set of diseases that are important causes of vision
      loss. Characterizing the transcripts, both annotated and novel, that are
      expressed in a given tissue has become vital for understanding the mechanisms
      underlying the pathology of disease. RESULTS: We sequenced RNA prepared from
      three normal human retinas and characterized the retinal transcriptome at an
      unprecedented level due to the increased depth of sampling provided by the RNA
      seq approach. We used a non-redundant reference transcriptome from all of the
      empirically-determined human reference tracks to identify annotated and novel
      sequences expressed in the retina. We detected 79,915 novel alternative splicing
      events, including 29,887 novel exons, 21,757 3' and 5' alternate splice sites,
      and 28,271 exon skipping events. We also identified 116 potential novel genes.
      These data represent a significant addition to the annotated human transcriptome.
      For example, the novel exons detected increase the number of identified exons by
      3%. Using a high-throughput RNA capture approach to validate 14,696 of these
      novel transcriptome features we found that 99% of the putative novel events can
      be reproducibly detected. Further, 15-36% of the novel splicing events maintain
      an open reading frame, suggesting they produce novel protein products.
      CONCLUSIONS: To our knowledge, this is the first application of RNA capture to
      perform large-scale validation of novel transcriptome features. In total, these
      analyses provide extensive detail about a previously uncharacterized level of
      transcript diversity in the human retina.

PMID- 23865677
TI  - Impact of various color LED flashlights and different lighting source to skin
      distances on the manual and the computer-aided detection of basal cell carcinoma
      borders.
AB  - BACKGROUND/AIMS: Quantitative analysis based on digital skin image has been
      proven to be helpful in dermatology. Moreover, the borders of the basal cell
      carcinoma (BCC) lesions have been challenging borders for the automatic detection
      methods. In this work, a computer-aided dermatoscopy system was proposed to
      enhance the clinical detection of BCC lesion borders. METHODS: Fifty cases of BCC
      were selected and 2000 pictures were taken. The lesion images data were obtained
      with eight colors of flashlights and in five different lighting source to skin
      distances (SSDs). Then, the image-processing techniques were used for automatic
      detection of lesion borders. Further, the dermatologists marked the lesions on
      the obtained photos. RESULTS: Considerable differences between the obtained
      values referring to the photographs that were taken at super blue and aqua green
      color lighting were observed for most of the BCC borders. It was observed that by
      changing the SSD, an optimum distance could be found where that the accuracy of
      the detection reaches to a maximum value. CONCLUSION: This study clearly
      indicates that by changing SSD and lighting color, manual and automatic detection
      of BCC lesions borders can be enhanced.

PMID- 23865678
TI  - Growth performance, carcass characteristics, fatty acid composition and CLA
      concentrations of lambs fed diets supplemented with different oil sources.
AB  - Quality food for human consumption will always be the aim for animal producers.
      Quantity and composition of fat deposits (fatty acid profile) strongly influences
      meat quality in ruminants, especially via increasing conjugated linoleic acid
      (CLA) concentration, which is known to have beneficial anticarcinogenic,
      antiatherogenic, antidiabetic and cholesterol reduction properties for human
      health. Awassi lambs are one of the main and most consumed meat sources in the
      Middle East area; however, studies addressing the fat content of CLA and methods
      to enhance its concentrations in this breed are still rare. For this reason, the
      aim of this study was to evaluate the effect of adding two different oil sources
      (soybean oil (SBO) and sunflower oil (SFO) at two levels (1.8 and 3%)) on growth
      performance, carcass characteristics and fatty acid profile of fat in Awassi
      lambs. Oil supplementation had no effect on growth performance or carcass
      characteristics, while fatty acid composition changed according to the site of
      extraction. CLA concentrations were increased in the tail fat deposit, with 1.8%
      SBO and in intermuscular fat deposit with 3% SFO. Intermuscular fat is the one
      most naturally consumed by humans, serving to improve food quality. 

PMID- 23865679
TI  - Pediatric kidney transplantation in the developing world: challenges and
      solutions.
AB  - The prevalence of pediatric RRT and transplantation are low in developing
      countries, 6-12 and <1 to 5 per million child population (pmcp), respectively.
      This is due to low GDP/capita of <$10 000, government expenditure on health of
      <2.6-9% of GDP and paucity of facilities. The reported incidence of pediatric CKD
      and ESRD is <1.0-8 and 3.4-35 pmcp, respectively. RRT and transplantation are
      offered mostly in private centers in cities where HD costs $20-100/session and
      transplants $10 000-20 000. High costs and long distance to centers results in
      treatment refusal in up to 35% of the cases. In this backdrop 75-85% of children
      with ESRD are disfranchised from RRT and transplantation. Our center initiated an
      integrated dialysis-transplant program funded by a community-government
      partnership where RRT and transplantation was provided "free of cost" with life
      long follow-up and medication. Access to free RRT at doorsteps and
      transplantation lead to societal acceptance of transplantation as the therapy of
      choice for ESRD. This enabled us to perform 475 pediatric transplants in 25 years
      with 1- and 5-year graft survival of 96% and 81%, respectively. Our model shows
      that pediatric transplantation is possible in developing countries when freely
      available and accessible to all who need it in the public sector.

PMID- 23865680
TI  - Homology modeling, docking studies and molecular dynamic simulations using
      graphical processing unit architecture to probe the type-11 phosphodiesterase
      catalytic site: a computational approach for the rational design of selective
      inhibitors.
AB  - Phosphodiesterase 11 (PDE11) is the latest isoform of the PDEs family to be
      identified, acting on both cyclic adenosine monophosphate and cyclic guanosine
      monophosphate. The initial reports of PDE11 found evidence for PDE11 expression
      in skeletal muscle, prostate, testis, and salivary glands; however, the tissue
      distribution of PDE11 still remains a topic of active study and some controversy.
      Given the sequence similarity between PDE11 and PDE5, several PDE5 inhibitors
      have been shown to cross-react with PDE11. Accordingly, many non-selective
      inhibitors, such as IBMX, zaprinast, sildenafil, and dipyridamole, have been
      documented to inhibit PDE11. Only recently, a series of dihydrothieno[3,2
      d]pyrimidin-4(3H)-one derivatives proved to be selective toward the PDE11
      isoform. In the absence of experimental data about PDE11 X-ray structures, we
      found interesting to gain a better understanding of the enzyme-inhibitor
      interactions using in silico simulations. In this work, we describe a
      computational approach based on homology modeling, docking, and molecular
      dynamics simulation to derive a predictive 3D model of PDE11. Using a Graphical
      Processing Unit architecture, it is possible to perform long simulations, find
      stable interactions involved in the complex, and finally to suggest guideline for
      the identification and synthesis of potent and selective inhibitors. 

PMID- 23865681
TI  - On-chip colorimetric detection of Cu2+ ions via density-controlled plasmonic core
      satellites nanoassembly.
AB  - We report on an on-chip colorimetric method for the detection and analysis of
      Cu(2+) ions via the targeted assembly of plasmonic silver nanoparticles (2.6 nm
      satellites) on density-controlled plasmonic gold nanoparticles (50 nm cores) on a
      glass substrate. Without any ligand modification of the nanoparticles, by
      directly using an intrinsic moiety (carboxylate ion, COO(-)) surrounded with
      nanoparticles, the method showed a high selectivity for Cu(2+), resulting in a
      nearly 2 times greater optical response compared to those of other metal ions via
      the targeted core-satellites assembly. By modulating the surface chemistry, it
      was possible to control the density of core gold nanoparticles on the surface,
      thus permitting easy tuning of the optical responses induced by plasmon coupling
      generated between each core-satellites nanostructure. Using chips with a
      controlled optimal core density, we observed the remarkable scattering color
      changes of the chips from green to yellow and finally to orange with the increase
      of Cu(2+) concentration. The detection limits of the fabricated chips with
      controlled core densities (ca. 1821 and 3636 particles/100 MUm(2)) are 10 nM and
      10 pM, respectively, which are quite tunable and below the level of 20 MUM (or
      1.3 ppm) defined by the United States Environmental Protection Agency. The
      findings suggest that the method is a potentially promising protocol for
      detecting small molecules with target selectivity and the tunability of the
      detection limits by replacing with ligands and adjusting core densities. 

PMID- 23865682
TI  - The fatal poisoning pattern of Ankara (Turkey) and nearby cities from 2007 to
      June 2011: a retrospective study in forensic autopsies.
AB  - We aimed to obtain an outline of the nature and number of fatal poisonings which
      still appear to affect widely the population in Turkey. A total of 5921 forensic
      autopsies were performed between 2007 and 2011 in Ankara and nearby cities and
      366 of them were fatal poisonings (219 male, 147 female). Most of the cases were
      between 41 and 60 years old (n = 84). Most of the fatalities were reported during
      winter months (48.1%). Carbon monoxide exposure was the most common reason
      (66.7%) within all the causes followed by medicine and narcotics (13.9%).
      Postmortem blood alcohol concentrations in ethyl and methyl alcohol poisonings
      were 385.1 +/- 61.9 and 206.8 +/- 138.9 mg/dL, respectively. The most common
      location of deaths was home (71.3%). Fatal poisonings have been a growing global
      problem because of some shortcomings about the socioeconomic conditions and
      increasing illicit drug abuse. The level of education, socioeconomic conditions,
      and legal approaches are very important for the prevention fatal poisonings.

PMID- 23865683
TI  - Total synthesis and full histone deacetylase inhibitory profiling of Azumamides A
      E as well as beta2- epi-Azumamide E and beta3-epi-Azumamide E.
AB  - Cyclic tetrapeptide and depsipeptide natural products have proven useful as
      biological probes and drug candidates due to their potent activities as histone
      deacetylase (HDAC) inhibitors. Here, we present the syntheses of a class of
      cyclic tetrapeptide HDAC inhibitors, the azumamides, by a concise route in which
      the key step in preparation of the noncanonical disubstituted beta-amino acid
      building block was an Ellman-type Mannich reaction. By tweaking the reaction
      conditions during this transformation, we gained access to the natural products
      as well as two epimeric homologues. Thus, the first total syntheses of azumamides
      B-D corroborated the originally assigned structures, and the synthetic efforts
      enabled the first full profiling of HDAC inhibitory properties of the entire
      selection of azumamides A-E. This revealed unexpected differences in the relative
      potencies within the class and showed that azumamides C and E are both potent
      inhibitors of HDAC10 and HDAC11. 

PMID- 23865684
TI  - Light-harvesting nanorods based on pheophorbide-appending cellulose.
AB  - In contrast to the success in artificial DNA- and peptide-based nanostructures,
      the ability of polysaccharides to self-assemble into one-, two-, and three
      dimensional nanostructures are limited. Here, we describe a strategy for
      designing and fabricating nanorods using a regioselectively functionalized
      cellulose derivative at the air-water interface in a stepwise manner. A
      semisynthetic chlorophyll derivative, pyro-pheophorbide a, was partially
      introduced into the C-6 position of the cellulose backbone for the design of
      materials with specific optical properties. Remarkably, controlled formation of
      cellulose nanorods can be achieved, producing light-harvesting nanorods that
      display a larger bathochromic shift than their solution counterparts. The results
      presented here demonstrate that the self-assembly of functionalized
      polysaccharides on surfaces could lead the nanostructures mimicking the naturally
      occurring chloroplasts. 

PMID- 23865685
TI  - Targeted expression of SbMATE in the root distal transition zone is responsible
      for sorghum aluminum resistance.
AB  - Aluminum (Al) toxicity is one of the major limiting factors for crop production
      on acid soils that comprise significant portions of the world's lands. Aluminum
      resistance in the cereal crop Sorghum bicolor is mainly achieved by Al-activated
      root apical citrate exudation, which is mediated by the plasma membrane localized
      citrate efflux transporter encoded by SbMATE. Here we precisely localize tissue-
      and cell-specific Al toxicity responses as well as SbMATE gene and protein
      expression in root tips of an Al-resistant near-isogenic line (NIL). We found
      that Al induced the greatest cell damage and generation of reactive oxygen
      species specifically in the root distal transition zone (DTZ), a region 1-3 mm
      behind the root tip where transition from cell division to cell elongation
      occurs. These findings indicate that the root DTZ is the primary region of root
      Al stress. Furthermore, Al-induced SbMATE gene and protein expression were
      specifically localized to the epidermal and outer cortical cell layers of the DTZ
      in the Al-resistant NIL, and the process was precisely coincident with the time
      course of Al induction of SbMATE expression and the onset of the recovery of
      roots from Al-induced damage. These findings show that SbMATE gene and protein
      expression are induced when and where the root cells experience the greatest Al
      stress. Hence, Al-resistant sorghum plants have evolved an effective strategy to
      precisely localize root citrate exudation to the specific site of greatest Al
      induced root damage, which minimizes plant carbon loss while maximizing
      protection of the root cells most susceptible to Al damage.

PMID- 23865686
TI  - Comparison of adherence and persistence with bimatoprost 0.01% versus bimatoprost
      0.03% topical ophthalmic solutions.
AB  - OBJECTIVE: To compare patient adherence and persistence with bimatoprost 0.01%, a
      new formulation that offers equivalent intraocular pressure-lowering efficacy to
      bimatoprost 0.03% and improved tolerability, with that of the original
      bimatoprost 0.03% formulation. METHODS: Pharmacy claims from a longitudinal
      database of prescription and medical claims for >115 million patients were
      analyzed. Patients with an initial (index) prescription for bimatoprost 0.01% or
      0.03% between April and June 2011, and with no claim for ophthalmic prostaglandin
      or prostamide analogs during the preceding 18 months, were identified. Treatment
      adherence was expressed as the proportion of days covered (PDC) with study
      medication over the first 365 days after the index prescription. Treatment
      persistence over the first 12 months following the index prescription was
      assessed using Kaplan-Meier analyses, assuming a 30 day grace period for
      prescription refill. Treatment status (on/off study medication) was determined
      monthly for 12 months post-index. RESULTS: In total, 6150 patients were assessed
      for treatment adherence and 7660 for persistence. Adherence was significantly
      better with bimatoprost 0.01% than bimatoprost 0.03% (mean PDC 0.540 vs. 0.438; p
      < 0.001). Significantly more patients had high adherence (PDC > 0.80) with
      bimatoprost 0.01% than 0.03% (29.1% vs. 17.3%; p < 0.001). Persistence was also
      significantly better with bimatoprost 0.01%, with 29.5% (95% confidence interval
      [CI]: 28.3%, 30.8%) versus 18.3% (95% CI: 16.8%, 19.9%) of patients remaining on
      continuous treatment for 12 months (p < 0.001). At 12 months, significantly more
      patients were 'on treatment' (continuing/restarting treatment) with bimatoprost
      0.01% than 0.03% (48.8% vs. 33.9%; p < 0.001). Sensitivity analyses demonstrated
      similar findings in cohorts of ocular hypotensive treatment-naive and elderly
      (>=65 years) patients. CONCLUSIONS: Bimatoprost 0.01% offers adherence and
      persistency advantages over bimatoprost 0.03% in patients requiring ocular
      hypotensive therapy. Study limitations included the observational design, lack of
      control for imbalances in patient characteristics, and assumption that
      prescription refill is synonymous with medication use.

PMID- 23865687
TI  - Predicting singlet-triplet energy splittings with projected Hartree-Fock methods.
AB  - Hartree-Fock (HF) and density functional theory (DFT) methods are known for
      having problems in predicting singlet-triplet energy splittings when the system
      displays significant diradical character. Multireference methods are
      traditionally advocated to deal with the spin-contamination problem inherent in
      broken-symmetry mean-field methods. In the present work, spin-contamination is
      rigorously eliminated by means of a symmetry projection approach, carried out in
      a variation-after-projection fashion, recently implemented in our research group.
      We here explore the performance of a variety of projected Hartree-Fock (PHF)
      approaches (SUHF, KSUHF, SGHF, and KSGHF) in predicting singlet-triplet energy
      gaps in a broad set of diradical systems: small diatomic molecules, carbenes and
      silenes, and a few larger molecules (trimethylenemethane and benzyne isomers).
      For most of these systems, accurate experimental data is available in the
      literature. Additionally, we assess the quality of the geometrical parameters
      obtained in SUHF-based optimizations for some of the systems considered. Our
      results indicate that PHF methods yield high-quality multireference wave
      functions, providing a good description of the ground state potential surface as
      well as an accurate singlet-triplet splitting gap, all within a modest mean-field
      computational cost. 

PMID- 23865688
TI  - Toll-deficient Drosophila is susceptible to Pythium insidiosum infection.
AB  - There is a paucity of animal models of pythiosis, a life-threatening disease of
      humans and animals, the immunopathogenesis of which is poorly understood. A
      pythiosis model was developed by injecting Toll (Tl)-deficient Drosophila
      melanogaster flies with Pythium insidiosum zoospores. The infected Tl mutant
      flies had significantly lower survival rates (73.7%) than did control flies. This
      study reveals the important role of Tl pathway activation in fly immune response
      to pythiosis. 

PMID- 23865689
TI  - An outbreak of feline infectious peritonitis in a Taiwanese shelter:
      epidemiologic and molecular evidence for horizontal transmission of a novel type
      II feline coronavirus.
AB  - Feline infectious peritonitis (FIP) is a fatal disease caused by feline
      coronavirus (FCoV) infection. FCoV can be divided into serotypes I and II. The
      virus that causes FIP (FIPV) is believed to occur sporadically and spread
      infrequently from cat to cat. Recently, an FIP outbreak from an animal shelter
      was confirmed in Taiwan. FCoV from all the cats in this shelter were analyzed to
      determine the epidemiology of this outbreak. Thirteen of 46 (28.2%) cats with
      typical signs of FIP were identified. Among them, seven cats were confirmed by
      necropsy and/or histopathological examinations. Despite the fact that more than
      one FCoV was identified in this multi-cat environment, the eight FIP cats were
      invariably found to be infected with a type II FCoV. Sequence analysis revealed
      that the type II FIPV detected from fecal samples, body effusions and
      granulomatous tissue homogenates from the cats that succumbed to FIP all harbored
      an identical recombination site in their S gene. Two of the cats that succumbed
      to FIP were found to harbor an identical nonsense mutation in the 3c gene. Fecal
      shedding of this type II virus in the effusive form of FIP can be detected up to
      six days before death. Taken together, our data demonstrate that horizontal
      transmission of FIPV is possible and that FIP cats can pose a potential risk to
      other cats living in the same environment. 

PMID- 23865690
TI  - Spiro-ring formation is catalyzed by a multifunctional dioxygenase in austinol
      biosynthesis.
AB  - Austinol, a fungal meroterpenoid derived from 3,5-dimethylorsellinic acid, has a
      unique chemical structure with a remarkable spiro-lactone ring system. Despite
      the recent identification of its biosynthetic gene cluster and targeted gene
      deletion experiments, the process for the conversion of protoaustinoid A (2), the
      first tetracyclic biosynthetic intermediate, to the spiro-lactone preaustinoid A3
      (7) has remained enigmatic. Here we report the mechanistic details of the enzyme
      catalyzed, stereospecific spiro-lactone ring-forming reaction, which is catalyzed
      by a non-heme iron-dependent dioxygenase, AusE, along with two flavin
      monooxygenases, the 5'-hydroxylase AusB and the Baeyer-Villiger monooxygenase
      AusC. Remarkably, AusE is a multifunctional dioxygenase that is responsible for
      the iterative oxidation steps, including the oxidative spiro-ring-forming
      reaction, to produce the austinol scaffold. 

PMID- 23865691
TI  - Genome-wide in silico screening for microRNA genetic variability in livestock
      species.
AB  - MicroRNAs are a class of non-coding RNAs that post-transcriptionally regulate
      target gene expression. Previous studies have shown that microRNA gene
      variability can interfere with its function, resulting in phenotypic variation.
      Polymorphisms within microRNA genes present a source of novel biomarkers for
      phenotypic traits in animal breeding. However, little is known about microRNA
      genetic variability in livestock species, which is also due to incomplete data in
      genomic resource databases. Therefore, the aim of this study was to perform a
      genome-wide in silico screening of genomic sources and determine the genetic
      variability of microRNA genes in livestock species using mirna sniper 3.0
      (http://www.integratomics-time.com/miRNA-SNiPer/), a new version of our
      previously developed tool. By examining Ensembl and miRBase genome builds, it was
      possible to design a tool-based generated search of 16 genomes including four
      livestock species: pig, horse, cattle and chicken. The analysis revealed 65
      polymorphisms located within mature microRNA regions in these four species,
      including 28% within the seed region in cattle and chicken. Polymorphic microRNA
      genes in cattle and chicken were further examined for mapping to quantitative
      trait loci regions associated with production and health traits. The developed
      bioinformatics tool enables the analysis of polymorphic microRNA genes and
      prioritization of potential regulatory polymorphisms and therefore contributes to
      the development of microRNA-based biomarkers in livestock species. The assembled
      catalog and the developed tool can serve the animal science community to
      efficiently select microRNA SNPs for further quantitative and molecular genetic
      evaluations of their phenotypic effects and causal associations with livestock
      production traits. 

PMID- 23865692
TI  - Short-term memory, working memory, and syntactic comprehension in aphasia.
AB  - Sixty-one people with aphasia were tested on 10 tests of short-term memory (STM)
      and for the ability to use syntactic structure to determine the meanings of 11
      types of sentences in three tasks-object manipulation, picture matching, and
      picture matching with self-paced listening. Multilevel models showed
      relationships between measures of the ability to retain and manipulate item and
      order information in STM and accuracy and reaction time (RT), and a greater
      relationship between these STM measures and accuracy and RT for several more
      complex sentence types in individual tasks. There were no effects of measures of
      STM that reflect the use of phonological codes or rehearsal on comprehension.
      There was only one effect of STM measures on self-paced listening times. There
      were double dissociations between performance on STM and individual comprehension
      tasks, indicating that normal STM is not necessary to perform normally on these
      tasks. The results are most easily related to the view that STM plays a
      facilitatory role in supporting the use of the products of the comprehension
      process to accomplish operations related to tasks. 

PMID- 23865693
TI  - Functional ecology of the ciliate Glaucomides bromelicola, and comparison with
      the sympatric species Bromeliothrix metopoides.
AB  - We investigated the ecology and life strategy of Glaucomides bromelicola (family
      Bromeliophryidae), a very common ciliate in the reservoirs (tanks) of bromeliads,
      assessing its response to food quality and quantity and pH. Further, we conducted
      competition experiments with the frequently coexisting species Bromeliothrix
      metopoides (family Colpodidae). In contrast to B. metopoides and many other
      colpodean ciliates, G. bromelicola does not form resting cysts, which jeopardizes
      this ciliate when its small aquatic habitats dry out. Both species form
      bactivorous microstomes and flagellate-feeding macrostomes. However, only G.
      bromelicola has a low feeding threshold and is able to adapt to different protist
      food. The higher affinity to the local bacterial and flagellate food renders it
      the superior competitor relative to B. metopoides. Continuous encystment and
      excystment of the latter may enable stable coexistence of both species in their
      natural habitat. Both are tolerant to a wide range of pH (4-9). These ciliates
      appear to be limited to tank bromeliads because they either lack resting cysts
      and vectors for long distance dispersal (G. bromelicola) and/or have highly
      specific food requirements (primarily B. metopoides). 

PMID- 23865695
TI  - Progression of major depression during pregnancy and postpartum: a preliminary
      study.
AB  - OBJECTIVE: The purpose of this pilot study was to investigate major depressive
      symptoms among a high-risk group of pregnant women managed at a tertiary care
      setting. METHOD: The study prospectively evaluated pregnant women who met DSM-IV
      criteria for a major depressive episode (MDE). Psychiatric measures for
      depression, anxiety and social impairment were administered at monthly intervals
      during pregnancy and immediate postpartum period. RESULTS: Twenty-four women
      provided longitudinal data from mid pregnancy to 2 months of postpartum period.
      86% of women were clinically symptomatic at the beginning of study during
      pregnancy and only 32% remained clinically symptomatic at 2 months following
      delivery reaching. This difference reached a statistical significance level p <
      0.001. Pregnant women with prior histories of major depression, comorbid anxiety
      disorder, histories of domestic violence, and those with uninvolved spouse or
      partners were more at-risk to be clinically symptomatic in the immediate
      postpartum period. CONCLUSIONS: In a group consisting of largely Latina women at
      a tertiary care setting, progression of major depression when treated with
      antidepressant medication(s) is that of an improvement from pregnancy to
      immediate postpartum period. Further longitudinal studies are needed to assess
      impact of clinical characteristics and treatment on major depression in larger
      diverse obstetric group.

PMID- 23865696
TI  - Effect of delayed initiation of gonadotropin in luteal long protocol on in vitro
      fertilization.
AB  - OBJECTIVE: To evaluate whether delayed initiation of gonadotropin in luteal long
      protocol affected the outcome of in vitro fertilization (IVF). STUDY DESIGN:
      Prospective randomized study at the reproductive centre of a university-based
      hospital. Eighty-five subfertile women undergoing IVF embryo transfer after a
      standardized gonadotropin-releasing hormone agonists (GnRHa) long protocol. The
      patients were randomized into group A (stimulated 3 weeks after GnRHa
      administration) and group B (stimulated 2 weeks after GnRHa administration),
      according to the time of gonadotropin initiation after GnRHa-mediated pituitary
      suppression. The main outcome measures were clinical pregnancy and live birth
      rates. RESULTS: There were no significant differences in baseline characteristics
      such as age, body mass index and basal follicle-stimulating hormone (bFSH)
      between the two groups. In group B, the days of gonadotropin stimulation were
      significantly greater than that in group A (p < 0.05), while the total dose of
      gonadotropin in group A was comparable to that in group B. Serum luteinizing
      hormone was lower and follicle-stimulating hormone higher in group A than in
      group B (p < 0.05) on initiation day. There were no significant differences in
      hormone profile measurements between the two groups. Moreover, the clinical
      pregnancy rate, implantation rate, live birth rate, miscarriage rate and moderate
      ovarian hyperstimulation syndrome rate were not significantly different between
      the groups. CONCLUSION: Delay of gonadotropin stimulation in a standard long
      protocol may increase clinical efficiency, without significantly changing
      clinical outcome.

PMID- 23865694
TI  - Retinoic acid-producing, ex-vivo-generated human tolerogenic dendritic cells
      induce the proliferation of immunosuppressive B lymphocytes.
AB  - While much is known about tolerogenic dendritic cell effects on forkhead box
      protein 3 (FoxP3)+ regulatory T cells, virtually nothing is known about their
      effects on another arm of immunoregulation that is mediated by a subpopulation of
      immunosuppressive B cells. These cells suppress rheumatoid arthritis, lupus and
      inflammatory bowel disease in mice, and functional defects have been reported in
      human lupus. We show that co-stimulation-impaired tolerogenic dendritic cells
      that prevent and reverse type 1 diabetes mellitus induce the proliferation of
      human immunosuppressive B cells in vitro. We also show that the suppressive
      properties of these B cells concentrate inside the CD19+ CD24+ B cell population
      and more specifically inside the CD19+ CD24+ CD38+ regulatory B cell population.
      We discovered that B cell conversion into suppressive cells in vitro is partially
      dependent on dendritic cell production of retinoic acid and also that CD19+ CD24+
      CD38+ B regulatory cells express retinoic acid receptors. Taken together, our
      data suggest a model whereby part of the immunosuppressive properties of human
      tolerogenic dendritic cells could be mediated by retinoic acid which, in addition
      to its known role in favouring T cell differentiation to FoxP3+ regulatory T
      cells, acts to convert B cells into immunosuppressive cells.

PMID- 23865697
TI  - The effect of continuous subcutaneous recombinant PTH (1-34) infusion during
      pregnancy on calcium homeostasis - a case report.
AB  - OBJECTIVE: We describe calcium homeostasis during pregestation and gestation in a
      woman with iatrogenic hypoparathyroidism, treated with continuous subcutaneous
      recombinant parathyroid hormone (PTH) (1-34) infusion. RESULTS: The requirement
      for PTH did not fluctuate much during pregnancy and was essential for maintaining
      normal calcium and phosphorus serum levels. CONCLUSIONS: This study documents the
      insufficiency of PTH-related protein (PTHrP) or other gestation-related hormones
      to compensate for PTH deficiency in hypoparathyroid women, and the successful
      utilization of continuous subcutaneous recombinant PTH (1-34) infusion to achieve
      normal calcium homeostasis during gestation. Clinical trials with PTH replacement
      in such circumstances are warranted.

PMID- 23865698
TI  - Lantz et al. respond.

PMID- 23865699
TI  - Health and the built environment: 10 years after.

PMID- 23865700
TI  - Smokers who try e-cigarettes to quit smoking: findings from a multiethnic study
      in Hawaii.
AB  - OBJECTIVES: We characterized smokers who are likely to use electronic or "e
      "cigarettes to quit smoking. METHODS: We obtained cross-sectional data in 2010
      2012 from 1567 adult daily smokers in Hawaii using a paper-and-pencil survey.
      Analyses were conducted using logistic regression. RESULTS: Of the participants,
      13% reported having ever used e-cigarettes to quit smoking. Smokers who had used
      them reported higher motivation to quit, higher quitting self-efficacy, and
      longer recent quit duration than did other smokers. Age (odds ratio [OR] = 0.98;
      95% confidence interval [CI] = 0.97, 0.99) and Native Hawaiian ethnicity (OR =
      0.68; 95% CI = 0.45, 0.99) were inversely associated with increased likelihood of
      ever using e-cigarettes for cessation. Other significant correlates were higher
      motivation to quit (OR = 1.14; 95% CI = 1.08, 1.21), quitting self-efficacy (OR =
      1.18; 95% CI = 1.06, 1.36), and ever using US Food and Drug Administration (FDA)
      approved cessation aids such as nicotine gum (OR = 3.72; 95% CI = 2.67, 5.19).
      CONCLUSIONS: Smokers who try e-cigarettes to quit smoking appear to be serious
      about wanting to quit. Despite lack of evidence regarding efficacy, smokers treat
      e-cigarettes as valid alternatives to FDA-approved cessation aids. Research is
      needed to test the safety and efficacy of e-cigarettes as cessation aids.

PMID- 23865701
TI  - Monitoring the sodium content of restaurant foods: public health challenges and
      opportunities.
AB  - We reviewed methods of studies assessing restaurant foods' sodium content and
      nutrition databases. We systematically searched the 1964-2012 literature and
      manually examined references in selected articles and studies. Twenty-six (5.2%)
      of the 499 articles we found met the inclusion criteria and were abstracted. Five
      were conducted nationally. Sodium content determination methods included
      laboratory analysis (n = 15), point-of-purchase nutrition information or
      restaurants' Web sites (n = 8), and menu analysis with a nutrient database (n =
      3). There is no comprehensive data system that provides all information needed to
      monitor changes in sodium or other nutrients among restaurant foods. Combining
      information from different sources and methods may help inform a comprehensive
      system to monitor sodium content reduction efforts in the US food supply and to
      develop future strategies.

PMID- 23865702
TI  - Food sources of saturated fat and the association with mortality: a meta
      analysis.
AB  - We summarized the data related to foods high in saturated fat and risk of
      mortality. We searched Cochrane Library, MEDLINE, EMBASE, and ProQuest for
      studies from January 1952 to May 2012. We identified 26 publications with
      individual dietary data and all-cause, total cancer, or cardiovascular mortality
      as endpoints. Pooled relative risk estimates demonstrated that high intakes of
      milk, cheese, yogurt, and butter were not associated with a significantly
      increased risk of mortality compared with low intakes. High intakes of meat and
      processed meat were significantly associated with an increased risk of mortality
      but were associated with a decreased risk in a subanalysis of Asian studies. The
      overall quality of studies was variable. Associations varied by food group and
      population. This may be because of factors outside saturated fat content of
      individual foods. There is an ongoing need for improvement in assessment tools
      and methods that investigate food sources of saturated fat and mortality to
      inform dietary guidelines. 

PMID- 23865703
TI  - Caine responds.

PMID- 23865704
TI  - Talman et al. respond.

PMID- 23865705
TI  - Lung cancer efforts need stronger emphasis on reducing radon exposure.

PMID- 23865706
TI  - Effects of proximate foreclosed properties on individuals' weight gain in
      Massachusetts, 1987-2008.
AB  - OBJECTIVES: We assessed the extent to which living near foreclosed properties is
      associated with individuals' subsequent weight gain. METHODS: We linked health
      and address information on 2068 Framingham Offspring Cohort members (7830
      assessments) across 5 waves (1987-2008) to records of all Massachusetts
      foreclosures during that period. We used counts of lender-owned foreclosed
      properties within 100 meters of participants' homes to predict body mass index
      (BMI; defined as weight in kilograms divided by the square of height in meters)
      and the odds of being overweight (BMI >= 25), adjusted for individual and area
      level covariates. RESULTS: Mean BMI increased from 26.6 in 1987-1991 to 28.5 in
      2005-2008; overweight prevalence increased from 59.0% to 71.3%. Foreclosures were
      within 100 meters of 159 (7.8%) participants' homes on 187 occasions (1.8%), in
      42 municipalities (21%). For each additional foreclosure, BMI increased by 0.20
      units (95% confidence interval [CI] = 0.03, 0.36), and the odds ratio for being
      overweight associated with proximity to a foreclosure was 1.77 (95% CI = 1.02,
      3.05). CONCLUSIONS: We found a robust association between living near
      foreclosures and BMI, suggesting that neighbors' foreclosures may spur weight
      gain.

PMID- 23865707
TI  - Quadrivalent human papillomavirus vaccine uptake in adolescent boys and maternal
      utilization of preventive care and history of sexually transmitted infections.
AB  - OBJECTIVES: We examined whether maternal utilization of preventive care and
      history of sexually transmitted infections (STIs) predicted quadrivalent human
      papillomavirus vaccine (HPV4) uptake among adolescent boys 1 year following the
      recommendation for permissive use of HPV4 for males. METHODS: We linked maternal
      information with electronic health records of 254 489 boys aged 9 to 17 years who
      enrolled in Kaiser Permanente Southern California health plan from October 21,
      2009, through December 21, 2010. We used multivariable Poisson regression with
      robust error variance to examine whether HPV4 initiation was associated with
      maternal uptake of influenza vaccine, Papanicolaou (Pap) screening, and history
      of STIs. RESULTS: We identified a modest but statistically significant
      association between initiation of HPV4 series and maternal receipt of influenza
      vaccine (rate ratio [RR] = 1.16; 95% confidence interval [CI] = 1.07, 1.26) and
      Pap screening (RR = 1.13; 95% CI = 1.01, 1.26). Boys whose mothers had a history
      of genital warts were more likely to initiate HPV4 (RR = 1.47; 95% CI = 0.93,
      2.34), although the association did not reach statistical significance (P = .1).
      CONCLUSIONS: Maternal utilization of preventive care and history of genital warts
      may influence HPV4 uptake among adolescent boys. The important role of maternal
      health characteristics and health behaviors needs be considered in intervention
      efforts to increase vaccine uptake among boys.

PMID- 23865708
TI  - Emerging Hispanic health paradoxes.

PMID- 23865709
TI  - Income inequality and mortality: results from a longitudinal study of older
      residents of Sao Paulo, Brazil.
AB  - OBJECTIVES: We determined whether community-level income inequality was
      associated with mortality among a cohort of older adults in Sao Paulo, Brazil.
      METHODS: We analyzed the Health, Well-Being, and Aging (SABE) survey, a sample of
      community-dwelling older adults in Sao Paulo (2000-2007). We used survival
      analysis to examine the relationship between income inequality and risk for
      mortality among older individuals living in 49 districts of Sao Paulo. RESULTS:
      Compared with individuals living in the most equal districts (lowest Gini
      quintile), rates of mortality were higher for those living in the second
      (adjusted hazard ratio [AHR] = 1.44, 95% confidence interval [CI] = 0.87, 2.41),
      third (AHR = 1.96, 95% CI = 1.20, 3.20), fourth (AHR = 1.34, 95% CI = 0.81,
      2.20), and fifth quintile (AHR = 1.74, 95% CI = 1.10, 2.74). When we imputed
      missing data and used poststratification weights, the adjusted hazard ratios for
      quintiles 2 through 5 were 1.72 (95% CI = 1.13, 2.63), 1.41 (95% CI = 0.99,
      2.05), 1.13 (95% = 0.75, 1.70) and 1.30 (95% CI = 0.90, 1.89), respectively.
      CONCLUSIONS: We did not find a dose-response relationship between area-level
      income inequality and mortality. Our findings could be consistent with either a
      threshold association of income inequality and mortality or little overall
      association.

PMID- 23865710
TI  - Effect of interfaces on the melting of PEO confined in triblock PS-b-PEO-b-PS
      copolymers.
AB  - Block copolymers form nanostructures that have interesting physical properties
      because they combine, for a single compound, the complementary features brought
      by each block. However, in order to fully exploit these properties, the physical
      state of each kind of domain must be precisely controlled. In this work, triblock
      PS-b-PEO-b-PS copolymers consisting of a central poly(ethylene oxide) (PEO) block
      covalently bonded to polystyrene (PS) blocks were synthesized by Atom Transfer
      Radical Polymerization. Their morphology was investigated by X-ray scattering and
      TEM experiments whereas their thermodynamic behavior was characterized by DSC. A
      strong decrease of both the melting temperature and the degree of crystallinity
      of PEO, due to its confinement between the PS domains, was observed and analyzed
      with a modified Gibbs-Thomson equation, following the approaches used for fluids
      confined in porous media. The existence of an amorphous bound layer, a few
      nanometers thick, at the PEO/PS interface, that does not undergo any phase
      transition in the temperature range investigated, accounts for both the melting
      temperature depression and the decrease of crystallinity upon confinement. This
      interfacial layer may significantly affect the mechanical and transport
      properties of these block copolymers that find applications as solid polymer
      electrolytes in batteries for example. Moreover, the value obtained for the solid
      PEO/liquid PEO surface tension is lower than those previously published but is
      thermodynamically consistent with the surface tensions of polymers at the
      solid/vapor and liquid/vapor interfaces. 

PMID- 23865711
TI  - Analysis of copy number variants by three detection algorithms and their
      association with body size in horses.
AB  - BACKGROUND: Copy number variants (CNVs) have been shown to play an important role
      in genetic diversity of mammals and in the development of many complex phenotypic
      traits. The aim of this study was to perform a standard comparative evaluation of
      CNVs in horses using three different CNV detection programs and to identify
      genomic regions associated with body size in horses. RESULTS: Analysis was
      performed using the Illumina Equine SNP50 genotyping beadchip for 854 horses.
      CNVs were detected by three different algorithms, CNVPartition, PennCNV and
      QuantiSNP. Comparative analysis revealed 50 CNVs that affected 153 different
      genes mainly involved in sensory perception, signal transduction and cellular
      components. Genome-wide association analysis for body size showed highly
      significant deleted regions on ECA1, ECA8 and ECA9. Homologous regions to the
      detected CNVs on ECA1 and ECA9 have also been shown to be correlated with human
      height. CONCLUSIONS: Comparative analysis of CNV detection algorithms was useful
      to increase the specificity of CNV detection but had certain limitations
      dependent on the detection tool. GWAS revealed genome-wide associated CNVs for
      body size in horses.

PMID- 23865712
TI  - Au@TiO2-CdS ternary nanostructures for efficient visible-light-driven hydrogen
      generation.
AB  - We report a new type of Au@TiO2-CdS ternary nanostructure by decorating CdS
      nanoparticles onto Au@TiO2 core-shell structures. In comparison to that of binary
      structures such as CdS-TiO2 and Au@TiO2, these ternary nanostructures exhibit a
      remarkably high photocatalytic H2-generation rate under visible-light
      irradiation. The enhanced photocatalytic activity is attributed to the unique
      ternary design, which builds up a transfer path for the photoexcited electrons of
      CdS to the core Au particles via the TiO2 nanocrystal bridge and thus effectively
      suppresses the electron-hole recombination on the CdS photocatalyst. This
      internal electron-transfer pathway (CdS -> TiO2 -> Au) eliminates the need for
      the postdeposition of the metal cocatalyst because the core Au nanoparticles can
      act as the interior active catalyst for proton reduction toward hydrogen
      evolution. We believe that our work demonstrates a promising way for the rational
      design of metal-semiconductor hybrid photocatalysts that can achieve a high
      photocatalytic efficiency for use in solar fuels production. 

PMID- 23865713
TI  - Indeterminate tcdB using a Clostridium difficile PCR assay: a retrospective
      cohort study.
AB  - BACKGROUND: C. difficile (CD) real-time polymerase chain reaction (PCR) for toxin
      B gene (tcdB) is more sensitive, and reduces turnaround time when compared to
      toxin immunoassay. We noted typical amplification curves with high tcdB cycle
      thresholds (Ct) and low endpoints (Ept) that are labeled negative by the
      Xpert((r)) C. difficile assay (Cepheid) and undertook this study to determine
      their significance. METHODS: We defined an indeterminate CD assay result as
      detection of a typical PCR amplification curve with an Ept >10 that was
      interpreted as negative by the Xpert((r)) assay. Samples with indeterminate
      Xpert((r)) result were collected for 5 months and retested by Xpert((r)),
      cultured for toxigenic CD, and isolates subjected to PCR ribotyping, detection of
      toxin genes and multilocus variable-number tandem repeat analysis (MLVA) typing.
      Chart reviews were completed to assess if patients met the Society of Healthcare
      Epidemiology of America and the Infectious Diseases Society of America CD
      infection (CDI) clinical case definition. Illness severity was compared with tcdB
      Ct and culture results. RESULTS: During the 5-month study period, 48/3620 (1%) of
      specimens were indeterminate and 387/3620 (11%) were positive. Of the 48 patients
      with indeterminate results, 39 (81%) met the clinical case definition of CDI, and
      7 of these (18%) met criteria for severe CDI. Toxigenic stool cultures were
      positive for 86% (6/7) of patients with severe CDI, 19% (6/32) of patients with
      non-severe CDI, and 44% (4/9) of patients who did not meet the clinical case
      definition of CDI (p = 0.002). Lower tcdB Ct and higher Ept were associated with
      greater likelihood of toxigenic culture positivity (p = 0.03) and more severe
      symptoms (p = 0.06). Indeterminate results were not associated with a particular
      technologist or instrument module, or CD strain type. CONCLUSIONS: A subset of
      specimens (1%) using the Xpert((r)) C. difficile assay have typical amplification
      curves and are interpreted as negative. At least one-third of these results are
      associated with positive CD culture. The mechanism of these indeterminate results
      is not technique-related, equipment-related, or due to particular CD strains.
      Clinicians should be aware that even PCR testing has the potential to miss CDI
      cases and further highlights the importance of clinical context when interpreting
      results.

PMID- 23865714
TI  - Abnormal expression of Pygopus 2 correlates with a malignant phenotype in human
      lung cancer.
AB  - BACKGROUND: Pygopus 2 (Pygo2) is a Pygo family member and an important component
      of the Wnt signaling transcriptional complex. Despite this data, no clinical
      studies investigating Pygo2 expression in lung cancer have yet been reported.
      METHODS: In the present study, the expression patterns of Pygo2 were evaluated by
      immunochemistry in 168 patients with non-small cell lung cancer (NSCLC). We used
      small interfering RNA (siRNA) to specifically silence Pygo2, and investigated its
      effect on cell growth by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay and flow cytometry analysis in human lung cancer cell lines.
      RESULTS: Immunohistochemical analysis showed low expression of Pygo2 in normal
      lung tissues and increased nuclear expression in lung cancer tissues, either with
      or without perinuclear expression. Abnormal Pygo2 expression was associated with
      poor differentiation and a high Tumor (T), Node (N) and Metastases (M) stage in
      NSCLC patients, and correlated with poor prognosis. Using MTT assay we observed
      that Pygo2 downregulation inhibited cell proliferation; in addition, flow
      cytometry analysis showed that Pygo2 knockdown induced apoptosis and increased
      numbers of G1-phase cells and a reduction in S-phase cells. CONCLUSIONS: We
      therefore conclude that abnormal Pygo2 protein expression may be a marker for
      advanced NSCLC. Furthermore, Pygo2 knockdown suppresses cell growth.

PMID- 23865715
TI  - Folate-based near-infrared fluorescent theranostic gemcitabine delivery.
AB  - A series of heptamethine cyanine (1-3) derivatives bearing a carbamate ethyl
      disulfide group and gemcitabine, an anticancer drug, have been newly synthesized.
      Their disulfide bonds are readily cleaved by various thiols including
      glutathione, to result in a subsequent decomposition of the carbamate into amine
      followed by release of the active gemcitabine, which can be monitored by the
      fluorescence changes. In the biological experiment, prodrug 1 is preferentially
      up-taken by folate-positive KB cells over folate-negative A549 cells via receptor
      mediated endocytosis to release gemcitabine causing cell death and to emit
      fluorescence in endoplasmic reticulum. Moreover, it is selectively accumulated in
      the KB cells which were treated to mice by dorsal subcutaneous injection. This
      drug delivery system is a new theranostic agent, wherein both therapeutic effect
      and drug uptake can be easily monitored at the subcellular level, by in vivo and
      in vitro fluorescence imaging. 

PMID- 23865716
TI  - Pure laparoscopic right hepatectomy in a living donor.
AB  - After reporting the first laparoscopic hepatectomy in a living donor for
      pediatric liver transplantation, we now report a case of pure laparoscopic right
      hepatectomy for adult transplantation. A 50-year-old female volunteered for
      living donation to her sister who suffered from primary biliary cirrhosis. The
      volume of the planned hepatic graft (segments 5-8) was 620 cm(3) , representing
      56% of her entire liver. Five ports were used in the donor to perform the
      operative procedure. The right hepatic artery and portal vein were isolated.
      Parenchymal division was performed using an ultrasonic dissector, bipolar
      coagulation and clips for hemostasis. Cholangiography was performed and the right
      bile duct was cut at the level of a marker thread. The right liver graft was
      placed in a bag and removed through a 10-cm suprapubic incision. The veins of
      segments 5 and 8 were recanalized and the graft was transplanted in the
      recipient. The postoperative course was uneventful for both the donor and
      recipient. This case offers evidence that the right liver can be procured via a
      total laparoscopic approach. This technique may allow for an early rehabilitation
      for the living donor.

PMID- 23865717
TI  - Complete sequence analysis of two cryptic plasmids from Bifidobacterium
      kashiwanohense JCM 15439 (type strain) isolated from healthy infant feces.
AB  - Bifidobacterial plasmids reported so far are derived from a limited number of
      strains and plasmids of bifidobacterial type strains isolated from humans are
      unknown. We found that Bifidobacterium kashiwanohense JCM 15439 (type strain)
      isolated from a healthy infant contained two cryptic plasmids, designated pBBKW-1
      and pBBKW-2. We determined and analyzed the complete sequences of both plasmids.
      pBBKW-1 (7716 bp) was predicted to replicate by a rolling-circle mechanism and
      encode six protein-coding genes, two of which are putative replication proteins.
      pBBKW-1 seems to be a cointegrate plasmid containing two copies of the plasmid
      pMG1 from Bifidobacterium longum. pBBKW-2 (2920 bp) was predicted to encode six
      protein-coding genes and be a theta-type replicating plasmid, which has been
      reported to be more stable than a rolling circle-type replicating plasmid
      frequently found in bifidobacteria. Our finding will provide new insights into
      safe recombinant plasmid constructions for humans. 

PMID- 23865718
TI  - microRNA-181a is involved in insulin-like growth factor-1-mediated regulation of
      the transcription factor CREB1.
AB  - microRNAs are a class of small non-coding RNA molecules negatively regulating
      gene expression at post-transcriptional level in many tissues including the
      central nervous system. cAMP response element binding protein (CREB) is a key
      nuclear factor highly expressed in hippocampal neurons on which many signal
      pathways converge. Recent studies have found that microRNA-181a is rich in mature
      nerve cells, and bioinformatics analysis shows that the CREB1 mRNA 3'
      untranslated region (3'UTR) contains complementary sequence to the miR-181a seed
      region. In this study, we investigated whether miR-181a is a negative regulator
      for CREB1 expression in neurons. It was found that the expression of miR-181a was
      negatively correlated with Insulin-like growth factor-1 (IGF-1) and CREB1 in the
      Lewis rat hippocampus. miR-181a bound to CREB1 mRNA through a specific binding
      site in the 3'UTR sequence. The expression of CREB1 in PC12 cells was down
      regulated by transfection with a miR-181a mimic and up-regulated by a miR-181a
      inhibitor. A down-regulated miR-181a and an up-regulated CREB1 were observed in
      IGF-1-stimulated PC12 cells. And miR-181a inhibited dendritic growth of cultured
      hippocampus neurons. These suggest that miR-181a is involved in IGF-1-regulated
      CREB1 expression by targeting its mRNA 3'UTR. microRNAs (miRNAs) regulate gene
      expression at the post-transcriptional level and are involved in the central
      nervous system development. Here, we demonstrate that miR-181a can inhibit the
      expression of the transcription factor CREB1 by specifically targeting its mRNA
      3'UTR and inhibit the development of hippocampus neurons. Repressed expression of
      miR-181a is involved in IGF-1-mediated up-regulation of CREB1 in vivo and in
      vitro. These findings indicate that miR-181a could be a potential target for
      preventing neurodegenerative diseases. 

PMID- 23865719
TI  - Effect of ethnicity, gender and age on the amount and composition of residual
      skin surface components derived from sebum, sweat and epidermal lipids.
AB  - BACKGROUND/PURPOSE: The superficial layer on the skin surface, known as the acid
      mantle, comprises a mixture of sebum, sweat, corneocyte debris and constituents
      of natural moisturizing factor. Thus, the phrase 'residual skin surface
      components' (RSSC) is an appropriate term for the mixture of substances recovered
      from the skin surface. There is no general agreement about the effects of
      ethnicity, gender and age on RSSC. The aim of this human volunteer study was to
      evaluate RSSC in relation to ethnicity, gender and age. A suitable acquisition
      medium for RSSC collection was identified and samples of RSSC were subsequently
      analysed using gas chromatography-mass spectrometry (GC-MS) and gravimetry.
      METHODS: A total of 315 volunteers participated in the study from a range of self
      declared ethnic backgrounds. Six acquisition media were compared to determine the
      most suitable media for RSSC collection. The effect of age, gender and ethnicity
      on RSSC collection was evaluated by gravimetric analysis while GC-MS was used to
      determine the composition of RSSC. RESULTS: Of the six candidate materials
      assessed, cigarette paper provided the most practical and reproducible sample
      acquisition medium. There was no significant difference in the amount of RSSC
      collected when based on gender and ethnicity and no significant correlation
      between RSSC recovery and age. Up to 49 compounds were detected from human RSSC
      when analysed by GC-MS. CONCLUSIONS: The results of the present study suggest
      that RSSC can be effectively collected using cigarette paper and analysed by GC
      MS. Ethnicity, gender and age had no significant impact on the quantity of RSSC
      recovered from the skin surface.

PMID- 23865720
TI  - Transcatheter aortic valve implantation in surgically repaired double outlet
      right ventricle.
AB  - A 52-year-old male patient, with a medical history of surgically repaired double
      outlet right ventricle presented with severe aortic stenosis (AS) and hepatitis C
      with cirrhosis, presented with New York Heart Association Class IV heart failure.
      During evaluation for a liver transplant, he was deemed a poor surgical candidate
      due to his aortic valve disease and cirrhosis with model for end-stage liver
      disease score of 14. Transthoracic echocardiogram showed severe AS with a mean
      gradient of 62 mm Hg and calculated aortic valve area of 0.74 cm(2) with a normal
      ejection fraction of 65%. The patient underwent transfemoral implantation of a 23
      mm Edwards Sapien commercial heart valve with significant mean gradient reduction
      across the aortic valve from 62 to 13 mm Hg. The patient was observed in the
      coronary care unit and discharged home 2 days postprocedure with his clinical
      symptoms greatly improved.

PMID- 23865721
TI  - Workplace assessment of targeted violence risk: the development and reliability
      of the WAVR-21.
AB  - This study describes the development of the WAVR-21, a structured professional
      judgment guide for the assessment of workplace targeted violence, and presents
      initial interrater reliability results. The 21-item instrument codes both static
      and dynamic risk factors and change, if any, over time. Five critical items or
      red flag indicators assess violent motives, ideation, intent, weapons skill, and
      pre-attack planning. Additional items assess the contribution of mental disorder,
      negative personality factors, situational factors, and a protective factor.
      Eleven raters each rated 12 randomly assigned cases from actual files of
      workplace threat scenarios. Summary interrater reliability correlation
      coefficients (ICCs) for overall presence of risk factors, risk of violence, and
      seriousness of the violent act were in the fair to good range, similar to other
      structured professional judgment instruments. A subgroup of psychologists who
      were coders produced an ICC of 0.76 for overall presence of risk factors. Some of
      the individual items had poor reliability for both clinical and statistical
      reasons. The WAVR-21 appears to improve the structuring and organizing of
      empirically based risk-relevant data and may enhance communication and decision
      making. 

PMID- 23865722
TI  - Transfection efficiency of DNA enhanced by association with salt-free catanionic
      vesicles.
AB  - The interaction of DNA with salt-free tetradecyltrimethylammonium hydroxide and
      lauric acid lamellar vesicles with positive charges was investigated to probe
      potential applications of vesicles in DNA transfection. The aggregation
      morphology of the vesicles changes greatly with the addition of DNA due to the
      dissociation of anionic surfactants, as indicated by (1)H nuclear magnetic
      resonance, and the expelled surfactant molecules self-assemble into micelles at
      high concentrations of DNA. Salt-free cationic and anionic (catanionic) vesicles
      have a much higher binding saturation point with DNA at R = 2.3 (the ratio of DNA
      to the excess positive charge in vesicles) than formerly reported salt-containing
      systems, implying high transfection efficiency. DNA retains its native stretched
      state during the interaction process. This very interesting result shows that
      catanionic vesicles could help transport undisturbed and extended DNA molecules
      into the target cells, which is of great importance in gene delivery,
      nanomedicine field, and controlling the formation of certain morphological
      aggregates.

PMID- 23865723
TI  - Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.
AB  - The cannabinoid receptor type 2 (CB2) is a class A GPCR that was cloned in 1993
      while looking for an alternative receptor that could explain the pharmacological
      properties of Delta(9)-tetrahydrocannabinol. CB2 was identified among cDNAs based
      on its similarity in amino acid sequence to the CB1 receptor and helped provide
      an explanation for the established effects of cannabinoids on the immune system.
      In addition to the immune system, CB2 has widespread tissue expression and has
      been found in brain, peripheral nervous system, and gastrointestinal tract.
      Several "mixed" cannabinoid agonists are currently in clinical use primarily for
      controlling pain, and it is believed that selective CB2 agonism may afford a
      superior analgesic agent devoid of the centrally mediated CB1 effects. Thus,
      selective CB2 receptor agonists represent high value putative therapeutics for
      treating pain and other disease states. In this Perspective, we seek to provide a
      concise update of progress in the field. 

PMID- 23865724
TI  - Dynamics and thermodynamics of crystalline polymorphs. 2. beta-Glycine, analysis
      of variable-temperature atomic displacement parameters.
AB  - The molecular dynamics in the crystal and the thermodynamic functions of the beta
      polymorph of glycine have been determined from a combination of molecular
      translation-libration frequencies reflecting the temperature dependence of atomic
      displacement parameters (ADPs), with frequencies derived from ONIOM(DFT:PM3)
      calculations on a 15-molecule beta-glycine cluster. ADPs have been obtained from
      variable-temperature diffraction data to 0.5 A resolution collected with X-ray
      synchrotron (10-300 K) and sealed tube radiation (50-298 K). At the higher
      temperatures, the ADPs of beta-glycine from synchrotron are larger than those
      from sealed tube probably due to different experimental conditions. The lattice
      vibration frequencies from normal-mode analysis of ADPs and the internal
      vibration frequencies from ONIOM(B3LYP/6-311+G(2d,p):PM3) calculations agree with
      those from spectroscopy. Estimation of thermodynamic functions using the
      vibrational frequencies, the Einstein and Debye models of heat capacity, and the
      room-temperature compressibility provides C(p), H(vib), and S(vib) that agree
      with those from calorimetry. The beta-phase with higher H and G is found to be
      less stable than the alpha-phase in the temperature range of the experiment.

PMID- 23865725
TI  - Differences in rates of hypoglycemia and health care costs in patients treated
      with insulin aspart in pens versus vials.
AB  - OBJECTIVES: To study whether initiation of insulin aspart therapy with a pen vs.
      a vial/syringe has an impact on the risk of subsequent hypoglycemic episodes and
      health care costs. METHODS: This was a longitudinal, retrospective analysis of
      the MarketScan and IMS LifeLink health plan claims databases for patients with
      type 1 or type 2 diabetes who initiated insulin aspart with a pen or a
      vial/syringe. Included were adults (>=18 years) who had received no short-acting
      insulin for the 6 months prior to their index date (date of first claim for
      either treatment) and who initiated treatment with insulin aspart with a pen or
      with a conventional vial/syringe during the period from January 1, 2004, through
      December 31, 2007, based on outpatient pharmacy claims data. Patients were
      excluded if they did not have at least two claims for the index treatment during
      the 12 month post-index period. Hypoglycemic episodes were identified by any
      claim containing a diagnosis code for hypoglycemia. RESULTS: Analyses include
      6065 patients in the pen group and 5523 patients in the vial/syringe group in the
      MarketScan database and 4512 patients in the pen group and 3782 patients in the
      vial/syringe group in the LifeLink database. Vial/syringe use was associated with
      35% greater odds of at least one hypoglycemic episode than pen use in the
      MarketScan database (P < 0.001) and 44% greater odds in the LifeLink database (P
      < 0.001). Use of vials/syringes was associated with 89% and 62.7% greater health
      care costs for hypoglycemic events than use of pens, respectively (P < 0.001 for
      both databases). Patient groups were subject to selection bias as they did not
      have random assignment to treatment groups. CONCLUSIONS: In two independent
      claims databases, initiation of insulin aspart treatment with pen was associated
      with fewer hypoglycemic events and lower diabetes-related health care costs than
      initiation with vial/syringe.

PMID- 23865726
TI  - Superiority of fluticasone propionate/formoterol fumarate versus fluticasone
      propionate alone in patients with moderate-to-severe asthma: a randomised
      controlled trial.
AB  - OBJECTIVE: To demonstrate the efficacy and safety of fluticasone
      propionate/formoterol fumarate (flutiform) in a pressurised metered-dose inhaler
      (pMDI) compared to two formulations of the fluticasone propionate component
      (Skyepharma fluticasone [SKP FP] or Flovent, GlaxoSmithKline [GSK FP]) in adults
      and adolescents with moderate-to-severe asthma. METHODS: Patients included in the
      study were >=12 years, with symptomatic asthma for >=1 year, steroid-requiring,
      had a forced expiratory volume in the first second (FEV1) of 40% to 80%
      (inclusive) of predicted normal values, and documented reversibility within 12
      months of the study. Albuterol/salbuterol was given as rescue medication. The
      primary efficacy endpoint was the change in FEV1 from morning pre-dose at
      baseline (week 0) to 2 hours post-dose at week 12 for fluticasone/formoterol
      compared to SKP FP and, additionally, compared to GSK FP. RESULTS:
      Fluticasone/formoterol was demonstrated to be statistically significantly
      superior to SKP FP. The least squares (LS) mean difference in FEV1 from baseline
      pre-dose to 2 hours post-dose at week 12 was 0.161 L (95% CI: 0.078, 0.245, p <
      0.001). Fluticasone/formoterol also demonstrated superior efficacy against GSK FP
      (LS mean difference = 0.185 L, 95% CI: 0.102, 0.268, p < 0.001). Results from
      multiple secondary and tertiary efficacy endpoints assessing lung function,
      asthma symptoms, exacerbations and rescue medication use supported a superior
      efficacy of the fluticasone/formoterol combination over both fluticasone
      formulations. Treatment-emergent adverse events were lowest in the
      fluticasone/formoterol group (32.9%) compared to SKP FP (39.7%) or GSK FP
      (40.4%). CONCLUSIONS: Results from this study demonstrate that
      fluticasone/formoterol 250/10 ug b.i.d. provides superior efficacy compared to
      fluticasone alone for the management of moderate-to-severe asthma, with a safety
      profile similar to that of fluticasone monotherapy. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00649025; EudraCT number: 2007-005653-37.

PMID- 23865728
TI  - In vitro three-dimensional development of mouse molar tooth germs in a rotary
      cell culture system.
AB  - OBJECTIVE: In vitro tooth germ cultivation is an effective method to explore the
      mechanism of odontogenesis. The three-dimensional rotary cell culture system
      (RCCS) is typically used to culture simulated organs such as cartilage, skin, and
      bone. In this study, we established an in vitro tooth germ culture model using
      RCCS to investigate whether RCCS could provide an appropriate environment for
      tooth germ development in vitro. METHODS: Mandibular first molar tooth germs from
      1-day post-natal mice were cultured in RCCS for 3, 6, and 9 days. Tooth germ
      development was monitored via histology (hematoxylin & eosin staining),
      stereoscopic microscopy, and quantitative real-time PCR (RT-PCR). RESULTS: Tooth
      germs cultured in RCCS maintained their typical spatial shape. Blood vessels were
      maintained on the dental follicle surface surrounding the crown. After
      cultivation, thick layers of dentin and enamel were secreted. Compared with tooth
      germs grown in jaw, the tooth germs grown in RCCS exhibited no significant
      difference in DMP1 or FGF10 expression at all time points. CONCLUSIONS: Use of
      RCCS enhanced the development of tooth germs and allowed the tooth germs to
      maintain their spatial morphology. These results indicate that RCCS may be an
      effective culture system to investigate the mechanism of tooth development.

PMID- 23865727
TI  - Comparison of pharmacokinetics between new quinolone antibiotics: the
      zabofloxacin hydrochloride capsule and the zabofloxacin aspartate tablet.
AB  - OBJECTIVES: Zabofloxacin is being developed as a new fluoroquinolone antibiotic
      that is a potent and selective inhibitor of the essential bacterial type II
      topoisomerases and topoisomerase IV. Zabofloxacin is indicated for community
      acquired respiratory infections due to Gram-positive bacteria. The aim of this
      study was to compare the pharmacokinetics (PK) of the zabofloxacin hydrochloride
      400 mg capsule (DW224a, 366.7 mg as zabofloxacin) with the PK of the zabofloxacin
      aspartate 488 mg tablet (DW224aa, 366.5 mg as zabofloxacin) in healthy Korean
      male volunteers to assess the bioequivalence between the two drug formulations.
      METHODS: A randomized, open-label, single-dose, two-way crossover study was
      performed. The subjects received either DW224a or DW224aa according to their
      sequence group. Plasma concentrations of zabofloxacin were determined by liquid
      chromatography-tandem mass spectrometry. The maximum plasma concentrations
      (Cmax), the area under the plasma concentration versus time curve (AUC) from the
      time of dosing to 48 hours post-dosing (AUClast), and the AUC extrapolated to
      infinity (AUCinf) were determined from the plasma concentration-time profile.
      (ClinicalTrials.gov identifier: NCT01341249). RESULTS: Twenty-nine of the 32
      subjects enrolled completed the study. The Cmax. AUClast, and AUCinf (mean +/-
      SD) values of DW224a were 1889.7 +/- 493.4 ng/mL, 11,110  +/- 2,005.0 ng h/mL,
      and 11,287 +/- 2,012.6 ng h/mL, respectively, and those of DW224aa were 2005.0 +/
      341.3 ng/mL, 11,719  +/-  2,507.5 ng h/mL, and 11,913 +/- 2,544.8 ng h/mL,
      respectively. The geometric mean ratios (90% confidence intervals) of the Cmax.
      AUClast, and AUCinf were 1.08 (1.00-1.17), 1.05 (1.00-1.10), and 1.05 (1.00
      1.10), respectively, and were within the bioequivalence acceptance range of 0.8
      1.25. Both drugs were well tolerated with no serious adverse events. CONCLUSION:
      A single oral dose of DW224a or DW224aa to healthy volunteers appeared to be well
      tolerated. Both DW224a and DW224aa exhibited comparable PK profiles and were
      bioequivalent in terms of PK parameters. Further studies in patients are needed
      to corroborate the result of this study.

PMID- 23865729
TI  - Hepatitis E virus infection in two different regions of Indonesia with
      identification of swine HEV genotype 3.
AB  - Hepatitis E is an emerging disease with a high incidence globally. Few data are
      available on hepatitis E virus (HEV) infection in Indonesia. To obtain molecular
      information on HEV infection in two regions of Indonesia with different customs
      and swine breeding conditions, serum samples from 137 swine farm workers, 100
      blood donors and 100 swine (27 fecal samples also obtained) in Yogyakarta
      (Central Java) and from 12 and 64 swine farm workers, 42 and 135 local residents
      and 89 and 119 swine in Tulungagung (East Java) and Mengwi (Bali), respectively,
      from our previous study, were compared.Serological tests for anti-HEV antibodies
      by ELISA, HEV-RNA detection by RT-PCR and phylogenetic analysis were performed.
      The total prevalence of anti-HEV antibodies in humans was higher in Bali(11.6%)
      than in Java (5.1%; P=0.015). No significant differences in anti-HEV prevalence
      among swine farm workers and local residents in Java were found. The finding of
      swine HEV genotype 3 in specimens from Yogyakarta and genotype 4 from Tulungagung
      and Bali is somewhat different from other reports.We suggest other factors in
      addition to close contact with swine might play an important role in HEV
      transmission of non-endemic/related custom groups. To the best of our knowledge,
      this is the first report on swine HEV genotype 3 in Indonesia.

PMID- 23865731
TI  - Interleukin-6 and statin therapy: potential role in the management of COPD.

PMID- 23865732
TI  - Insights into the glycyl radical enzyme active site of benzylsuccinate synthase:
      a computational study.
AB  - The fumarate addition reaction, catalyzed by the enzyme benzylsuccinate synthase
      (BSS), is considered to be one of the most intriguing and energetically
      challenging reactions in biology. BSS belongs to the glycyl radical enzyme family
      and catalyzes the fumarate addition reaction, which enables microorganisms to
      utilize hydrocarbons as an energy source under anaerobic conditions.
      Unfortunately, the extreme sensitivity of the glycyl radical to oxygen has
      hampered the structural and kinetic characterization of BSS, thereby limiting our
      knowledge on this enzyme. To enhance our molecular-level understanding of BSS, a
      computational approach involving homology modeling, docking studies, and
      molecular dynamics (MD) simulations has been used to deduce the structure of
      BSS's catalytic subunit (BSSalpha) and illuminate the molecular basis for the
      fumarate addition reaction. We have identified two conserved and distinct binding
      pockets at the BSSalpha active site: a hydrophobic pocket for toluene binding and
      a polar pocket for fumaric acid binding. Subsequent dynamical and energetic
      evaluations have identified Glu509, Ser827, Leu390, and Phe384 as active site
      residues critical for substrate binding. The orientation of substrates at the
      active site observed in MD simulations is consistent with experimental
      observations of the syn addition of toluene to fumaric acid. It is also found
      that substrate binding tightens the active site and restricts the conformational
      flexibility of the thiyl radical, leading to hydrogen transfer distances
      conducive to the proposed reaction mechanism. The stability of substrates at the
      active site and the occurrence of feasible radical transfer distances between the
      thiyl radical, substrates, and the active site glycine indicate a substrate
      assisted radical transfer pathway governing fumarate addition. 

PMID- 23865733
TI  - Probiotics for the prevention of necrotizing enterocolitis in neonates: an 8-year
      retrospective cohort study.
AB  - WHAT IS KNOWN AND OBJECTIVE: Probiotic therapy has been shown to reduce morbidity
      and mortality of necrotizing enterocolitis (NEC) in premature infants in several
      international studies using various probiotic agents. The purpose of this
      study(*) is to describe our experience of using probiotic therapy in preventing
      NEC in infants with very low birth weight (VLBW) in a neonatal intensive care
      unit (NICU) and to evaluate whether our records provide evidence of effectiveness
      for probiotic therapy. METHODS: In a retrospective cohort study, the efficacy of
      probiotic therapy in preventing NEC in VLBW infants was investigated via chart
      review. A probiotic administration protocol using a three-strain (Streptococcus
      thermophilus, Bifidobacterium infantis and Bifidobacterium bifidum) supplement
      was implemented in August 2007. Patients admitted to the NICU from August 2003
      through July 2011 were screened. Primary outcomes are the morbidity and mortality
      of NEC. The secondary outcomes were severity of NEC and incidence of where infant
      feeds were stopped but NEC was not diagnosed (NEC scare). RESULTS AND DISCUSSION:
      There was a significant increased baseline risk of NEC development in the
      probiotics group, including younger gestational age, higher incidence of patent
      ductus arteriosus (PDA) and use of indomethacin. The incidence of NEC is similar
      between the control group (2.8%) and probiotics group (2.4%) (hazard ratio, 1.15;
      95% confidence interval [CI], 0.42, 3.12). Mortality of NEC is also not
      statistically different. Incidence of NEC scare was decreased from 2.8% in
      control group to 1.4% in probiotics group, although the difference was not
      statistically significant (P = 0.38). WHAT IS KNOWN AND CONCLUSION: Our findings
      suggest that probiotics are safe in NEC prevention in VLBW infants. We had no
      cases of infection related to the strains of bacteria used in our product. With
      the low incidence of NEC (2.8%) and NEC scare (2.8%) in our cohort, we do not
      have enough power to detect any change in outcome, particularly as our study was
      observational. However, it is hoped that our data give useful information for
      others on probiotic prophylactic therapy in the routine clinical management of
      VLBW infants.

PMID- 23865734
TI  - Morphology and molecular phylogeny of a new marine hypotrichous ciliate,
      Hypotrichidium paraconicum n. sp. (Ciliophora, Hypotrichia).
AB  - A new saline hypotrich, Hypotrichidium paraconicum n. sp., found in coastal
      waters near Hong Kong, China, was investigated with emphasis on its living
      morphology, infraciliature, ontogenesis, and phylogenetic position. A body that
      is pyriform, with a posterior end that is twisted helically toward the left, a
      distinct tail and a dark colour, characterizes H. paraconicum n. sp. The buccal
      cavity is prominent and the cortical granules, which are scattered or sparsely
      distributed, are colourless, round, and about 1 MUm in diam. The contractile
      vacuole is near the left middle of the cell and there are one or two frontal
      cirri, four meridional rows and five or six cirral rows which exhibit a left
      handed spiral and which are distributed in the posterior portion on both sides.
      Three dorsal kineties are distributed in the anterior portion of the dorsal side.
      In our molecular phylogenies, based on SSU rRNA gene sequences, the position of
      H. paraconicum n. sp. is rather poorly resolved, providing some indication of a
      relationship with Neokeronopsis aurea and Rubrioxytricha ferruginea, which fall
      into the assemblage of oxytrichids (s.l.). 

PMID- 23865735
TI  - Large normal alleles and SCA2 prevalence: lessons from a nationwide study and
      analysis of the literature.

PMID- 23865736
TI  - Predicting ambulance time of arrival to the emergency department using global
      positioning system and Google maps.
AB  - OBJECTIVE: To derive and validate a model that accurately predicts ambulance
      arrival time that could be implemented as a Google Maps web application. METHODS:
      This was a retrospective study of all scene transports in Multnomah County,
      Oregon, from January 1 through December 31, 2008. Scene and destination hospital
      addresses were converted to coordinates. ArcGIS Network Analyst was used to
      estimate transport times based on street network speed limits. We then created a
      linear regression model to improve the accuracy of these street network estimates
      using weather, patient characteristics, use of lights and sirens, daylight, and
      rush-hour intervals. The model was derived from a 50% sample and validated on the
      remainder. Significance of the covariates was determined by p < 0.05 for a t-test
      of the model coefficients. Accuracy was quantified by the proportion of estimates
      that were within 5 minutes of the actual transport times recorded by computer
      aided dispatch. We then built a Google Maps-based web application to demonstrate
      application in real-world EMS operations. RESULTS: There were 48,308 included
      transports. Street network estimates of transport time were accurate within 5
      minutes of actual transport time less than 16% of the time. Actual transport
      times were longer during daylight and rush-hour intervals and shorter with use of
      lights and sirens. Age under 18 years, gender, wet weather, and trauma system
      entry were not significant predictors of transport time. Our model predicted
      arrival time within 5 minutes 73% of the time. For lights and sirens transports,
      accuracy was within 5 minutes 77% of the time. Accuracy was identical in the
      validation dataset. Lights and sirens saved an average of 3.1 minutes for
      transports under 8.8 minutes, and 5.3 minutes for longer transports. CONCLUSIONS:
      An estimate of transport time based only on a street network significantly
      underestimated transport times. A simple model incorporating few variables can
      predict ambulance time of arrival to the emergency department with good accuracy.
      This model could be linked to global positioning system data and an automated
      Google Maps web application to optimize emergency department resource use. Use of
      lights and sirens had a significant effect on transport times.

PMID- 23865737
TI  - Long-term follow-up of 163 consecutive patients treated with isolated limb
      perfusion for in-transit metastases of malignant melanoma.
AB  - PURPOSE: The aim of the present study is to describe our experience with isolated
      limb perfusion (ILP) in the treatment of in-transit metastases of malignant
      melanoma and to determine prognostic factors for response, local progression,
      survival and toxicity. MATERIALS AND METHODS: A retrospective follow-up of all
      patients (n = 163) treated between January 1984 and December 2008 using data
      collected from individual patient records and the Swedish National Patient
      Register. RESULTS: Clinical response was evaluable in 155 patients, 65% had a
      complete response (CR) and 20% had a partial response (PR). Local progression
      occurred in 63% of the patients after a median time of 16 months. Negative
      prognostic factors in univariate analyses were proximal location of the primary
      tumour, >10 in-transit metastases and if there was no CR after ILP. In
      multivariate analysis, proximal location of the primary tumour and no CR after
      ILP were significant prognostic factors. Median cancer-specific survival was 30
      months, and negative prognostic factors in univariate analyses were male gender,
      positive lymph node status, systemic metastases, bulky tumour, >10 in-transit
      metastases and if there was no CR after ILP. In multivariate analysis, positive
      lymph node status, bulky tumour and no CR after ILP were significant prognostic
      factors. A majority (97%) of the patients had a Wieberdink grade II-III local
      toxicity. Four patients underwent limb amputation after a median of 19 months,
      none because of toxicity. CONCLUSION: We found that ILP is a safe method with a
      high response rate for the treatment of patients with in-transit metastases of
      malignant melanoma.

PMID- 23865738
TI  - Occiput posterior position diagnosis: vaginal examination or intrapartum
      sonography? A clinical review.
AB  - The occiput posterior (OP) position is one of the most frequent malposition
      during labor. During the first stage of labor, the fetal head may stay in the OP
      position in 30% of the cases, but of these only 5-7% remains as such at time of
      delivery. The diagnosis of OP position in the second stage of labor is made
      difficult by the presence of the caput succedaneum or scalp hair, both of which
      may give some problem in the identification of fetal head sutures and fontanels
      and their location in relationship to maternal pelvic landmarks. The capability
      of diagnosing a fetus in OP position by digital examination has been extremely
      inaccurate, whereas an ultrasound approach, transabdominal, transperineal and
      transvaginal, has clearly shown its superior diagnostic accuracy. This is true
      not only for diagnosis of malpositions, detected in both first and second stage
      of labor, but also in cases of marked asynclitism.

PMID- 23865739
TI  - Interaction of the biosurfactant, Surfactin with betaines in aqueous solution.
AB  - The interactions between the lipopeptide Surfactin and four betaines, N-dodecyl
      N,N-dimethyl-3-ammonio-1-propanesulfonate (SDDAB), N-tetradecyl-N,N-dimethyl-3
      ammonio-1-propanesulfonate (STDAB), N-hexadecyl-N,N-dimethyl-3-ammonio-1
      propanesulfonate (SHDAB), and N-dodecyl-N,N-dimethyl-2-ammonio-acetate (C12BE)
      are studied by surface tension and small-angle neutron scattering (SANS). SDDAB,
      STDAB, and SHDAB have the same headgroup but different hydrophobic chains. C12BE
      has different headgroup but the same hydrophobic chain with SDDAB. According to
      the interfacial parameters calculated from surface tension, the synergism between
      Surfactin and betaine is relevant with the molecule structure of betaine and the
      mole ratio of them. For betaines, the optimum alkyl chain length (STDAB) and long
      enough separation between positive charge and negative charge in headgroup are
      responsible for highest synergetic interaction with Surfactin. The aggregates of
      individual Surfactin and the mixtures of Surfactin and sulfopropyl betaines are
      predicted to be spherical based on the packing parameter (pp) and the average
      packing parameter (P(av)), which is in close qualitative agreement with SANS data
      analysis, while Surfactin/C12BE forms ellipsoidal micelles due to the smaller
      headgroup of C12BE.

PMID- 23865741
TI  - Charging of quantum dots by sulfide redox electrolytes reduces electron injection
      efficiency in quantum dot sensitized solar cells.
AB  - In quantum dot (QD) sensitized solar cells (QDSSCs), redox electrolytes act as
      hole scavengers to regenerate the QD ground state from its oxidized form, thus
      enabling a continuous device operation. However, unlike molecular sensitizers,
      QDs also have redox-active trap states within the band gap, which can be charged
      in the presence of redox electrolyte. The effects of electrolyte induced charging
      of QDs on the performance of QDSSCs have not been reported. Here, using steady
      state and time-resolved absorption and emission spectroscopy, we show that
      CdSe/CdS3MLZnCdS2MLZnS2ML core/multishell QDs are charged in the presence of
      sulfide electrolytes due to the reduction of surface states. As a result, exciton
      lifetimes in these QDs are shortened due to an Auger recombination process. Such
      charging induced fast Auger recombination can compete effectively with electron
      transfer from QDs to TiO2 and reduce the electron injection efficiency in QDSSCs.
      We believe that the reported charging effects are present for most colloidal
      nanocrystals in the presence of redox media and have important implications for
      designing QD-based photovoltaic and photocatalytic devices. 

PMID- 23865740
TI  - De novo sequencing and transcriptome analysis of the desert shrub, Ammopiptanthus
      mongolicus, during cold acclimation using Illumina/Solexa.
AB  - BACKGROUND: Ammopiptanthus mongolicus (Maxim. ex Kom.) Cheng f., an evergreen
      broadleaf legume shrub, is distributed in Mid-Asia where the temperature can be
      as low as -30 degrees C during the winter. Although A. mongolicus is an ideal
      model to study the plant response to cold stress, insufficient genomic resources
      for this species are available in public databases. To identify genes involved in
      cold acclimation (a phenomenon experienced by plants after low temperature
      stress), a high-throughput sequencing technology was applied. RESULTS: We
      sequenced cold-treated and control (untreated) samples of A. mongolicus, and
      obtained 65,075,656 and 67,287,120 high quality reads, respectively. After de
      novo assembly and quantitative assessment, 82795 all-unigenes were finally
      generated with an average length of 816 bp. We then obtained functional
      annotations by aligning all-unigenes with public protein databases including NR,
      SwissProt, KEGG and COG. Differentially expressed genes (DEGs) were investigated
      using the RPKM method. Overall, 9309 up-regulated genes and 23419 down-regulated
      genes were identified. To increase our understanding of these DEGs, we performed
      GO enrichment and metabolic pathway enrichment analyses. Based on these results,
      a series of candidate genes involved in cold responsive pathways were selected
      and discussed. Moreover, we analyzed transcription factors, and found 720 of them
      are differentially expressed. Finally, 20 of the candidate genes that were up
      regulated and known to be associated with cold stress were examined using qRT
      PCR. CONCLUSIONS: In this study, we identified a large set of cDNA unigenes from
      A. mongolicus. This is the first transcriptome sequencing of this non-model
      species under cold-acclimation using Illumina/Solexa, a next-generation
      sequencing technology. We sequenced cold-treated and control (untreated) samples
      of A. mongolicus and obtained large numbers of unigenes annotated to public
      databases. Studies of differentially expressed genes involved in cold-related
      metabolic pathways and transcription factors facilitate the discovery of cold
      resistance genes.

PMID- 23865742
TI  - Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal
      and meningococcal meningitis.
AB  - BACKGROUND: Bacterial meningitis is characterized by an intense inflammatory
      reaction contributing to neuronal damage. The aim of this study was to obtain a
      comparative analysis of cytokines and chemokines in patients with pneumococcal
      (PM) and meningococcal meningitis (MM) considering that a clear difference
      between the immune response induced by these pathogens remains unclear. METHODS:
      The cyto/chemokines, IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-10, IL-1Ra,
      CXCL8/IL-8, CCL2/MCP-1, CLL3/MIP-1alpha, CCL4/MIP-1gamma and G-CSF, were measured
      in cerebrospinal fluid (CSF) samples from patients with PM and MM. Additionally,
      a literature review about the expression of cytokines in CSF samples of patients
      with MB was made. RESULTS: Concerning cytokines levels, only IFN-gamma was
      significantly higher in patients with Streptococcus pneumoniae compared to those
      with Neisseria meningitidis, regardless of the time when the lumbar puncture (LP)
      was made. Furthermore, when samples were compared considering the timing of the
      LP, higher levels of TNF-alpha (P <0.05) were observed in MM patients whose LP
      was made within 48 h from the initial symptoms of disease. We also observed that
      the index of release of cyto/chemokines per cell was significantly higher in PM.
      From the literature review, it was observed that TNF-alpha, IL-1beta and IL-6 are
      the best studied cytokines, while reports describing the concentration of the
      cytokine IL-2, IL-1Ra, G-CSF and CCL4/MIP-1beta in CSF samples of patients with
      bacterial meningitis were not found. CONCLUSION: The data obtained in this study
      and the previously published data show a similar profile of cytokine expression
      during PM and MM. Nevertheless, the high levels of IFN-gamma and the ability to
      release high levels of cytokines with a low number of cells are important factors
      to be considered in the pathogenesis of PM and thereby should be further
      investigated. Moreover, differences in the early response induced by the
      pathogens were observed. However, the differences observed are not sufficient to
      trigger changes in the current therapy of corticosteroids adopted in both the PM
      and MM.

PMID- 23865743
TI  - CXCR7 is induced by hypoxia and mediates glioma cell migration towards SDF
      1alpha.
AB  - BACKGROUND: Glioblastomas, the most common and malignant brain tumors of the
      central nervous system, exhibit high invasive capacity, which hinders effective
      therapy. Therefore, intense efforts aimed at improved therapeutics are ongoing to
      delineate the molecular mechanisms governing glioma cell migration and invasion.
      METHODS: In order to perform the studies, we employed optimal cell culture
      methods and hypoxic conditions, lentivirus-mediated knockdown of protein
      expression, Western Blot analysis, migration assays and immunoprecipitation. We
      determined statistical significance by unpaired t-test. RESULTS: In this report,
      we show that U87MG, LN229 and LN308 glioma cells express CXCR7 and that exposure
      to hypoxia upregulates CXCR7 protein expression in these cell lines. CXCR7
      expressing U87MG, LN229 and LN308 glioma cells migrated towards stromal-derived
      factor (SDF)-1alpha/CXCL12 in hypoxic conditions in the Boyden chamber assays.
      While shRNA-mediated knockdown of CXCR7 expression did not affect the migration
      of any of the three cell lines in normoxic conditions, we observed a reduction in
      the migration of LN229 and LN308, but not U87MG, glioma cells towards SDF-1alpha
      in hypoxic conditions. In addition, knockdown of CXCR7 expression in LN229 and
      LN308 glioma cells decreased levels of SDF-1alpha-induced phosphorylation of
      ERK1/2 and Akt. Inhibiting CXCR4 in LN229 and LN308 glioma cells that were
      knocked down for CXCR7 did not further reduce migration towards SDF-1alpha in
      hypoxic conditions and did not affect the levels of phosphorylated ERK1/2 and
      Akt. Analysis of immunoprecipitated CXCR4 from LN229 and LN308 glioma cells
      revealed co-precipitated CXCR7. CONCLUSIONS: Taken together, our findings
      indicate that both CXCR4 and CXCR7 mediate glioma cell migration towards SDF
      1alpha in hypoxic conditions and support the development of therapeutic agents
      targeting these receptors.

PMID- 23865744
TI  - Influence of sodium halides (NaF, NaCl, NaBr, NaI) on the photocatalytic
      performance of hydrothermally synthesized hematite photoanodes.
AB  - It has been suggested that a high concentration of Fe(3+) in solution, a low pH,
      and noncomplexing ions of high ionic strength are all essential for developing a
      high-quality hematite array. Our curiosity was piqued regarding the role of the
      electrolyte ions in the hydrothermal synthesis of hematite photoanodes. In this
      study, we prepared hematite photoanodes hydrothermally from precursor solutions
      of 0.1 M FeCl3 at pH 1.55 with a background electrolyte of 1.0 M sodium halide
      (NaF, NaCl, NaBr, or NaI). We compared the structures and properties of the as
      obtained hematite photoanodes with those of the material prepared in 1.0 M NaNO3,
      the most widely adopted electrolyte in previous studies. Among our studied
      systems, we found that the hematite photoanode prepared in NaCl solution was the
      only one possessing properties similar to those of the sample obtained from the
      NaNO3 solution-most importantly in terms of photoelectrochemical performance (ca.
      0.2 mA/cm(2) with +0.4 V vs SCE). The hematites obtained from the NaF, NaBr, and
      NaI solutions exhibited much lower (by approximately 2 orders of magnitude)
      photocurrent densities under the same conditions, possibly because of their
      relatively less ordered crystallinity and the absence of rodlike morphologies.
      Because the synthetic protocol was identical in each case, we believe that these
      two distinct features reflect the environments in which these hematite
      photoanodes were formed. Consistent with the latest studies reported in the
      literature of the X-ray photoelectron spectra of fast-frozen hematite colloids in
      aqueous solutions, it appears that the degree of surface ion loading at the
      electrolyte-hematite interface (Stern layer) is critical during the development
      of hematite photoanodes. We suspect that a lower ion surface loading benefits the
      hematite developing relatively higher-order and a rodlike texture, thereby
      improving the photoelectrochemical activity. 

PMID- 23865745
TI  - Effect of chronic smoking on lens nucleus as assessed by Pentacam HR lens
      densitometry in young adults.
AB  - OBJECTIVE: To evaluate the effects of chronic tobacco smoking on lens nucleus by
      Pentacam HR lens densitometry (LD) in young adults. DESIGN: Prospective cross
      sectional case series. METHODS: Thirty subjects (23 M, 7 F) who were chronic
      cigarette smokers (>=10 cigarettes/day for at least 2 years) (group 1) and
      another 30 subjects (23 M, 7 F) who did not smoke (group 2), were included in
      this study. The patients were matched for age and sex between the groups. The
      exclusion criteria were any history of ocular surgery, any systemic disorders and
      any ocular diseases except for mild refractive disorders. Lens densitometry
      measurements were done with the Pentacam HR (Oculus, Wetzlar, Germany). The
      Schirmer test and pachymetry measurements were also performed. RESULTS: Mean age
      of the patients for both groups was 28.90 +/- 8.20 years (range: 18-40 years).
      Mean lens densitometry (LD) measurements of Group 1 (chronic cigarette smoking
      group) were higher than those of Group 2 (control group) in all LD techniques;
      however only mean "peak" LD measurements showed a statistically significant
      difference between these two groups (Group 1: 8.67 +/- 0.61, Group 2: 8.44 +/-
      0.70, p = 0.04). The mean Schirmer test value was 12.43 +/- 5.60 mm in Group 1
      and 13.00 +/- 4.26 mm in Group 2 (p = 0.55). The mean central corneal thickness
      (CCT) value was 564.23 +/- 34.61 um in Group 1 and 550.47 +/- 32.94 um in Group 2
      (p = 0.03). DISCUSSION: The Pentacam HR LD seems to be an important option for
      the evaluation of lens nucleus in young adults, because it gives objective and
      quantitative data. CONCLUSION: Although chronic smoking increases lens nucleus
      density in young adults, the effect is not statistically significant when
      compared with the control group.

PMID- 23865746
TI  - Effects of dietary combination of corn and rice as whole crop silage and grain
      sources on carbohydrate digestion and nitrogen use in steers.
AB  - Four Holstein steers were used to evaluate the combination effects of whole crop
      corn (Cs) or rice (Rs) silage with steam-flaked corn (Cg) or rice (Rg) grain
      (four dietary treatments) on ruminal carbohydrate digestion, duodenal nitrogen
      (N) flow and plasma essential amino acid (EAA) concentration. The ruminal
      digestibility of starch and nonfiber carbohydrate (NFC) for Rs and Rg diets
      compared with Cs and Cg diets was greater, but that of neutral detergent fiber
      (aNDFom) was less. Because the ruminal disappearance of NFC plus aNDFom was
      similar across four dietary treatments, microbial N flow was not affected by the
      diets. There was an interaction of methionine (Met) flow by silage and grain
      sources: greatest for CsRg and least for RsRg diet, and blood plasma
      concentration of Met after feeding was lower for Rg than Cg diets. Postprandial
      reduction degree of plasma EAA varied with the diets and individual EAA. The Cs
      diets compared with the Rs diets tended to be greater in N retention because of
      greater digestible organic matter (OM) intake. These results suggest that silage
      source combined with corn or rice grain affects N use in steers through the
      digestible OM intake, and the kinds of limiting AA may differ among the
      combination of silage and grain sources. 

PMID- 23865747
TI  - Call for antimicrobial stewardship in solid organ transplantation.

PMID- 23865748
TI  - Ecological Inferences from a deep screening of the Complex Bacterial Consortia
      associated with the coral, Porites astreoides.
AB  - The functional role of the bacterial organisms in the reef ecosystem and their
      contribution to the coral well-being remain largely unclear. The first step in
      addressing this gap of knowledge relies on in-depth characterization of the coral
      microbial community and its changes in diversity across coral species, space and
      time. In this study, we focused on the exploration of microbial community
      assemblages associated with an ecologically important Caribbean scleractinian
      coral, Porites astreoides, using Illumina high-throughput sequencing of the V5
      fragment of 16S rRNA gene. We collected data from a large set of biological
      replicates, allowing us to detect patterns of geographical structure and resolve
      co-occurrence patterns using network analyses. The taxonomic analysis of the
      resolved diversity showed consistent and dominant presence of two OTUs affiliated
      with the order Oceanospirillales, which corroborates a specific pattern of
      bacterial association emerging for this coral species and for many other corals
      within the genus Porites. We argue that this specific association might indicate
      a symbiotic association with the adult coral partner. Furthermore, we identified
      a highly diverse rare bacterial 'biosphere' (725 OTUs) also living along with the
      dominant bacterial symbionts, but the assemblage of this biosphere is
      significantly structured along the geographical scale. We further discuss that
      some of these rare bacterial members show significant association with other
      members of the community reflecting the complexity of the networked consortia
      within the coral holobiont. 

PMID- 23865749
TI  - Plant Defensin type 1 (PDF1): protein promiscuity and expression variation within
      the Arabidopsis genus shed light on zinc tolerance acquisition in Arabidopsis
      halleri.
AB  - Plant defensins are recognized for their antifungal properties. However, a few
      type 1 defensins (PDF1s) were identified for their cellular zinc (Zn) tolerance
      properties after a study of the metal extremophile Arabidopsis halleri. In order
      to investigate whether different paralogues would display specialized functions,
      the A. halleri PDF1 family was characterized at the functional and genomic
      levels. Eleven PDF1s were isolated from A. halleri. Their ability to provide Zn
      tolerance in yeast cells, their activity against Fusarium oxysporum f. sp.
      melonii, and their level of expression in planta were compared with those of the
      seven A. thaliana PDF1s. The genomic organization of the PDF1 family was
      comparatively analysed within the Arabidopsis genus. AhPDF1s and AtPDF1s were
      able to confer Zn tolerance and AhPDF1s also displayed antifungal activity. PDF1
      transcripts were constitutively more abundant in A. halleri than in A. thaliana.
      Within the Arabidopsis genus, the PDF1 family is evolutionarily dynamic, in terms
      of gain and loss of gene copy. Arabidopsis halleri PDF1s display no superior
      abilities to provide Zn tolerance. A constitutive increase in AhPDF1 transcript
      accumulation is proposed to be an evolutionary innovation co-opting the
      promiscuous PDF1 protein for its contribution to Zn tolerance in A. halleri. 

PMID- 23865750
TI  - A dynamic G-quadruplex region regulates the HIV-1 long terminal repeat promoter.
AB  - G-Quadruplexes, noncanonical nucleic acid structures, act as silencers in the
      promoter regions of human genes; putative G-quadruplex forming sequences are also
      present in promoters of other mammals, yeasts, and prokaryotes. Here we show that
      also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional
      regulation with striking similarities to eukaryotic promoters and that treatment
      with a G-quadruplex ligand inhibits HIV-1 infectivity. Computational analysis on
      953 HIV-1 strains substantiated a highly conserved G-rich sequence corresponding
      to Sp1 and NF-kappaB binding sites. Biophysical/biochemical analysis proved that
      two mutually exclusive parallel-like intramolecular G-quadruplexes, stabilized by
      small molecule ligands, primarily fold in this region. Mutations disrupting G
      quadruplex formation enhanced HIV promoter activity in cells, whereas treatment
      with a G-quadruplex ligand impaired promoter activity and displayed antiviral
      effects. These findings disclose the possibility of inhibiting the HIV-1 LTR
      promoter by G-quadruplex-interacting small molecules, providing a new pathway to
      development of anti-HIV-1 drugs with unprecedented mechanism of action. 

PMID- 23865751
TI  - HIV incidence from the first population-based cohort study in India.
AB  - BACKGROUND: Understanding about who acquires new HIV infection and the
      determinants of why some persons get infected and others do not is fundamental to
      controlling HIV in the population. We assess HIV incidence and its associations
      in the population of a high HIV burden district in Andhra Pradesh state in
      southern India by a population-based longitudinal cohort study. METHODS: We re
      surveyed a population-based cohort of 12,617 adults in Guntur district of Andhra
      Pradesh for which we had reported a baseline HIV prevalence of 1.72% (rural
      1.64%, urban 1.89%) among the 15-49 years age group in 2004-2005. We conducted
      interviews to assess risk behaviour and performed HIV testing again in 2010-2011.
      We assessed the rate of new HIV infection and its associations using multiple
      logistic regression. RESULTS: The participation rate in the follow-up was 74.9%
      and 63.9% of the baseline rural and urban samples, respectively. Over a mean
      follow-up of 5.63 years, the incidence of HIV was 1.26 per 1000 person-years (95%
      CI 0.83-1.69), after adjusting for slight compositional bias in the follow-up
      sample. The incidence per 1000 person-years was higher among rural men (1.68)
      than urban men (0.85), and among rural women (1.28) than urban women (0.54). The
      strongest association with incidence was a HIV positive spouse in the baseline
      for both men (odds ratio 266, 95% CI 62-1137) and women (odds ratio 28, 95% CI 9
      88). Among men the other significant associations with HIV incidence were
      frequent use of condom for sex over the past 6 months, non-circumcision, more
      than one lifetime woman sex partner or ever visited sex worker, and transport
      related occupation; for women the other significant associations were having had
      HIV testing other than antenatal check-up, previously married but currently not,
      and tobacco use. CONCLUSION: These first population-based cohort incidence data
      from India suggest that rural areas of high HIV burden states would need more
      attention to prevent new HIV infections, and that spouses of HIV positive persons
      and some other risk groups need to be targeted more effectively by HIV prevention
      programmes.

PMID- 23865752
TI  - Catechol-functionalized chitosan/iron oxide nanoparticle composite inspired by
      mussel thread coating and squid beak interfacial chemistry.
AB  - Biological materials offer a wide range of multifunctional and structural
      properties that are currently not achieved in synthetic materials. Herein we
      report on the synthesis and preparation of bioinspired organic/inorganic
      composites that mimic the key physicochemical features associated with the
      mechanical strengthening of both squid beaks and mussel thread coatings using
      chitosan as an initial template. While chitosan is a well-known biocompatible
      material, it suffers from key drawbacks that have limited its usage in a wider
      range of structural biomedical applications. First, its load-bearing capability
      in hydrated conditions remains poor, and second it completely dissolves at pH <
      6, preventing its use in mild acidic microenvironments. In order to overcome
      these intrinsic limitations, a chitosan-based organic/inorganic biocomposite is
      prepared that mimics the interfacial chemistry of squid beaks and mussel thread
      coating. Chitosan was functionalized with catechol moieties in a highly
      controlled fashion and combined with superparamagnetic iron oxide (gamma-Fe2O3)
      nanoparticles to give composites that represent a significant improvement in
      functionality of chitosan-based biomaterials. The inorganic/organic (gamma
      Fe2O3/catechol) interfaces are stabilized and strengthened by coordination
      bonding, resulting in hybrid composites with improved stability at high
      temperatures, physiological pH conditions, and acid/base conditions. The
      inclusion of superparamagnetic particles also makes the composites stimuli
      responsive. 

PMID- 23865753
TI  - Modification of peptide and protein cysteine thiol groups by conjugation with a
      degradation product of ascorbate.
AB  - Ascorbate is an important water-soluble antioxidant, which when oxidized by
      reactive oxygen species is converted into dehydroascorbate (DHA). If not rapidly
      reduced back to ascorbate, DHA decomposes to a reactive 5-carbon compound (DHA*,
      +130 Da) that can modify reduced cysteinyl residues in peptides and proteins in
      vitro. The formation of cysteine adducts by DHA* was characterized by mass
      spectrometry using reduced insulin B-chain, alpha-lactalbumin, and hemoglobin.
      Mass spectrometry of DHA* modified insulin B-chain revealed the presence of one
      and two DHA* adducts. Enzymatic cleavage and tandem mass spectrometry of modified
      peptides allowed unambiguous localization of DHA* to the two cysteine residues in
      positions 7 and 19 of the insulin B-chain. Incubations of DHA with alpha
      lactalbumin revealed that approximately 25% of the protein population was in a
      reduced state and could be modified by DHA*. The adduct was assigned to the N
      terminally located cysteinyl residue in position 6. Incubation of hemoglobin with
      DHA followed by pepsin digestion and electrospray ionization tandem mass
      spectrometry (ESI-MSMS) of the peptide mixture allowed for the identification of
      three modified peptides. Tandem mass spectrometry of the modified peptides, two
      from the hemoglobin A-chain with identical mass and one from the hemoglobin B
      chain, gave a complete series of y-type fragment ions, which were assigned to the
      cysteine containing peptides (100)LLSHCL(105) (A-chain), (101)LSHCLL(106) (A
      chain), and (111)VCVLAHHFGKE(121) (B-chain). Although the DHA* adduct was lost
      from the peptides derived from alpha-lactalbumin and hemoglobin before
      fragmentation of the peptide bond, carbamidomethylation of the proteins prior to
      incubation with DHA abolished the formation of DHA*-protein adducts and confirmed
      that the target was indeed the cysteine thiol group. Future studies are focused
      on the modification of proteins by DHA* in cells and in vivo. 

PMID- 23865754
TI  - Remembering Ernie Mazzaferri - A Personal Reflection.
AB  - NA.

PMID- 23865755
TI  - The third National Food Consumption Survey, INRAN-SCAI 2005-06: major dietary
      sources of nutrients in Italy.
AB  - INTRODUCTION: To promote healthy food consumption patterns, information is
      required on the contribution of food groups to total nutrient intake. The
      objective of this paper is to identify the main dietary sources of nutrients in
      the diet of the population in Italy. METHODS: Data collected through individual
      food records within the INRAN-SCAI 2005-06 survey were required. The final sample
      included 3323 subjects aged 0.1-97.7 years. RESULTS: The percentage contributed
      by each food category to the intake of energy, dietary fibre and of 26 nutrients
      was calculated. Above 3 years of age, the main contributors to macro- and micro
      nutrient intakes were similar among the various age-sex groupings with few
      exceptions. CONCLUSION: These data might be used to develop specific strategies
      for Italy in order to increase the intake of dietary fibre and to decrease that
      of total fats and of sugars in the population.

PMID- 23865756
TI  - Clinical implications of predominant polarity and the polarity index in bipolar
      disorder: a naturalistic study.
AB  - OBJECTIVE: Predominant polarity (PP) is an important variable in maintenance
      treatment of bipolar disorder (BD). This study aimed at determining the role of
      polarity index (PI), a metric indicating antimanic versus antidepressive
      prophylactic potential of drugs, in clinical decision-making. METHOD: Two hundred
      and fifty-seven of 604 (43%) of patients with BD-I or II fulfilled criteria for
      manic (MPP) or depressive PP (DPP). The PI, representing the ratio of number
      needed to treat (NNT) for depression prevention to NNT for mania prevention, was
      calculated for patients' current treatment. MPP and DPP groups were compared
      regarding sociodemographic, clinical and therapeutic characteristics. RESULTS:
      One hundred and forty-three patients (55.6%) fulfilled criteria for DPP and 114
      (44.4%) for MPP. Total PI, Antipsychotics' PI, and mood stabilizers PI were
      higher, indicating a stronger antimanic action, in MPP. MPP presented higher
      prevalence of BD-I, male gender, younger age, age at onset and at first
      hospitalization, more hospitalizations, primary substance misuse, and psychotic
      symptoms. DP correlated with BD-II, depressive onset, primary life events,
      melancholia, and suicide attempts. CONCLUSION: The results confirm the usefulness
      of the PI. In this large sample, clinical differences among these groups justify
      differential treatment approach. The PI appears to be a useful operationalization
      of what clinicians do for maintenance therapy in BD.

PMID- 23865757
TI  - Stress-related responses in Alexandrium tamarense cells exposed to environmental
      changes.
AB  - Organisms tend to be sensitive to drastic changes in environmental conditions.
      For unicellular microorganisms, variations in physico-chemical conditions are
      particularly challenging and may result in acclimation, entrance into quiescence,
      or death through necrotic or autocatalytic pathways. This study focuses on the
      thecate dinoflagellate Alexandrium tamarense. Cellular responses to oxidative,
      thermal, and nutrient stress were characterized using stress indicators, such as
      pigment content, efficiency of photosystem II or production of reactive oxygen
      species (ROS), as well as hallmarks of apoptosis including activity of caspase
      like enzymes and expression of a metacaspase gene homolog. The formation of
      temporary cysts, a survival strategy of short-term quiescence, was also
      monitored. Cellular responses appeared to depend on multifactorial influences
      where type and intensity of stimulus as well as position in cell cycle may act in
      combination. Sequences of events observed implicate ROS production as a key
      determinant of stress-related pathways, playing potential roles in intracellular
      signaling, formation of temporary cysts, or cellular damage. Variations observed
      in caspase-like activities and metacaspase gene expression did not appear to be
      associated with programmed cell death pathways; our results suggest a wider range
      of functions for these proteases in phytoplankton cells, including roles in
      survival pathways and cell cycle progression. 

PMID- 23865758
TI  - Modulation of O-antigen chain length by the wzz gene in Escherichia coli O157
      influences its sensitivities to serum complement.
AB  - Escherichia coli O157 strains belonging to a distinct lineage and expressing
      different O-antigen (Oag) lengths were isolated. Although the function of wzz in
      E. coli has not been adequately investigated, this gene is known to be associated
      with regulation of Oag length. Using E. coli O157:H7 ATCC43888 (wild-type),
      several wzz mutants of E. coli O157, including a wzz deletion mutant, were
      generated and the relationship between the length of Oag modulated by the wzz
      gene and sensitivities to serum complement investigated. SDS-PAGE, immunoblot
      analyses and sensitivity tests to human serum complement were performed on these
      strains. The lengths of the O157-antigen could be modulated by the wzz gene
      mutations and were classified into long, intermediate and short groups. The short
      chain mutant was more serum sensitive than the wild-type strain and the other wzz
      mutants (P < 0.001). In conclusion, Oag chain length modulated by the wzz gene in
      E. coli O157 influences its sensitivities to serum complement. The present
      findings suggest that E. coli O157 strains with intermediate or long length Oag
      chains might show greater resistance to serum complement than those with short
      chains.

PMID- 23865759
TI  - Cervical arterial injury after strangulation--different types of arterial
      lesions.
AB  - After strangulation, cervical arterial injuries (CAI) are uncommon. We report
      three unusual cases where strangulation induced immediate stroke. CAI were
      examined using brain CT scan and Doppler ultrasonography in the three cases and
      then by autopsy in one of the victims. One of the two victims who survived the
      attempted strangulation had a unilateral carotid dissection, whereas in the other
      victim, no arterial dissection or thrombosis was observed. As regards the
      deceased victim, the autopsy confirmed the bilateral dissection showed on CT scan
      and Doppler ultrasonic examination and revealed that both carotid arteries were
      dilated up to two times the normal diameter. Microscopic examination showed a
      major bilateral hemorrhagic dissection of the media with obliterating fibrous
      endarteritis lesions associated with inflammatory damage. CT scan with
      arteriography does not demonstrate all the different types of arterial injury,
      particularly atheromatous embolism, direct compression, or prolonged spasm. Thus,
      traditional autopsy remains an essential forensic tool after strangulation to
      show the type of CAI. 

PMID- 23865760
TI  - Pregnancy and perinatal outcomes among women with multiple sclerosis: a
      retrospective case-controlled study in South Hungary.
AB  - OBJECTIVE: The aim of this study was to investigate the connections between
      multiple sclerosis (MS) and fertility, pregnancy. METHODS: The case histories and
      pregnancy complications in a sample of 65 treatment-naive pregnant women with MS
      in the period 1998-2012 were compared with an age-matched case-controlled
      analysis. Comparisons were made between primigravidas and multigravidas subjects.
      RESULTS: Our results revealed a higher rate of miscarriage (18.46%) in the first
      trimester in women with MS, and intrauterine death (7.69%) in the third
      trimester, as compared with women without MS (p < 0.001 and p = 0.035).
      CONCLUSIONS: These findings suggest that, the risk of miscarriages and
      intrauterine death may be disease-related not drug-related feature. Further
      studies are needed to determine to possible associated factors of miscarriages.

PMID- 23865761
TI  - Tonic GABA inhibition in hippocampal dentate granule cells: its regulation and
      function in temporal lobe epilepsies.
AB  - Both human and experimental evidence strongly supports the view of brain region-
      and cell-specific changes in tonic GABA inhibition in temporal lobe epilepsies
      (TLE). This 'tonic' form of signalling is not time-locked to presynaptic action
      potentials, which depends upon detection of ambient GABA by extrasynaptic GABAA
      receptors (GABAA Rs). Extrasynaptic GABAA Rs have distinct physiological and
      pharmacological features, including high GABA-binding affinity and low
      desensitization and a variety of the specific subunit combinations (alpha4delta
      ,alpha6delta-,alpha5gamma-,epsilon-containing receptors). These features closely
      contribute to the function of tonic GABA current, which is preserved properly or
      increased in dentate gyrus in models of TLE, even in the face of a loss of
      synaptic inhibition and inhibitory interneurones. Markedly reduced tonic GABA
      inhibition may facilitate an episode of epilepsy, while persistent elevated tonic
      inhibition may contribute to the onset of spontaneous recurrent seizures. In
      dentate granule cells, tonic GABA inhibition is positively modulated by
      endogenous neurosteroids and other factors, which undergo changes related to
      hormonal status after TLE. Tonic inhibition regulates neuronal excitability
      through its effects on membrane potential by both offsetting the threshold and
      reducing the frequency of action potentials and input resistance. Therefore,
      extrasynaptic GABAA Rs are expected to be the most important pharmacological
      targets in TLE. It is likely that both elevate the ambient GABA concentration and
      potentiate the tonic currents, contributing to the antiepileptic effects.

PMID- 23865762
TI  - Natural products: tools and more special issue.

PMID- 23865765
TI  - Modeling risk-related knowledge in tunneling projects.
AB  - Knowledge on failure events and their associated factors, gained from past
      construction projects, is regarded as potentially extremely useful in risk
      management. However, a number of circumstances are constraining its wider use.
      Such knowledge is usually scarce, seldom documented, and even unavailable when it
      is required. Further, there exists a lack of proven methods to integrate and
      analyze it in a cost-effective way. This article addresses possible options to
      overcome these difficulties. Focusing on limited but critical potential failure
      events, the article demonstrates how knowledge on a number of important potential
      failure events in tunnel works can be integrated. The problem of unavailable or
      incomplete information was addressed by gathering judgments from a group of
      experts. The elicited expert knowledge consisted of failure scenarios and
      associated probabilistic information. This information was integrated using
      Bayesian belief-networks-based models that were first customized in order to deal
      with the expected divergence in judgments caused by epistemic uncertainty of
      risks. The work described in the article shows that the developed models that
      integrate risk-related knowledge provide guidance as to the use of specific
      remedial measures. 

PMID- 23865766
TI  - Design and application of a novel PNA probe for the detection at single cell
      level of JAK2V617F mutation in Myeloproliferative Neoplasms.
AB  - BACKGROUND: Mutation(s) of the JAK2 gene (V617F) has been described in a
      significant proportion of Philadelphia negative Myeloproliferative Neoplasms
      (MPN) patients and its detection is now a cornerstone in the diagnostic
      algorithm. METHODS: We developed a novel assay based on peptide nucleic acid
      (PNA) technology coupled to immuno-fluorescence microscopy (PNA-FISH) for the
      specific detection at a single cell level of JAK2-mutation thus improving both
      the diagnostic resolution and the study of clonal prevalence. RESULTS: Using this
      assay we found a percentage of mutated CD34+ cells ranging from 40% to 100% in
      Polycythemia Vera patients, from 15% to 80% in Essential Thrombocythemia and from
      25% to 100% in Primary Myelofibrosis. This method allows to distinguish, with a
      high degree of specificity, at single cell level, between CD34+ progenitor stem
      cells harbouring the mutated or the wild type form of JAK2 in NPM patients.
      CONCLUSIONS: This method allows to identify multiple gene abnormalities which
      will be of paramount relevance to understand the pathophysiology and the
      evolution of any type of cancer.

PMID- 23865767
TI  - Synthesis, structure, and optical activity of HPM-1, a pure silica chiral
      zeolite.
AB  - 2-Ethyl-1,3,4-trimethylimidazolium is a poor organic structure-directing agent in
      the synthesis of pure silica zeolites using fluoride as a mineralizer at 150 
      degrees C. Under these conditions only ill-crystallized solids are obtained after
      long hydrothermal treatments (several weeks). It disappoints despite its
      relatively large size, conformational rigidity, and intermediate
      hydrophilic/hydrophobic character, attributes which would qualify it as a
      promising structure-directing agent, according to prior investigations. By
      raising the crystallization temperature to 175  degrees C under otherwise
      identical conditions, crystallization is dramatically accelerated. Depending on
      the water/silica ratio and crystallization time, two different materials are
      obtained: the recently reported pure silica polymorph of the chiral STW-type
      zeolite, HPM-1, and the new layered organosilicate, HPM-2. Prolonged heating
      transforms these phases into the small-pore ITW-type zeolite, while no signs of
      the SOF-type zeolite (formally built from the same layers as STW) was found. A
      complete physicochemical and structural characterization of the as-made chiral
      HPM-1 zeolite is provided, and the proposed stabilization of this zeolite by
      polarization of the Si-O bond is supported by the observed deviation from
      tetrahedrality. HPM-1 is optically active, and a study of several crystallites by
      Mueller matrix microscopy shows that their optical activity can be individually
      measured and that this technique could be useful for the assessment of the
      enantiomeric purity of a microcrystalline powder. 

PMID- 23865768
TI  - Longitudinal growth on an everolimus- versus an MMF-based steroid-free
      immunosuppressive regimen in paediatric renal transplant recipients.
AB  - Concerns have been raised that mammalian target of rapamycin inhibitors in
      pediatric transplant recipients might interfere with longitudinal bone growth by
      inhibition of growth factor signaling and growth plate chondrocyte proliferation.
      We therefore undertook a prospective nested, case-control study on longitudinal
      growth over 2 years in steroid-free pediatric renal transplant recipients.
      Fourteen patients on a steroid-free maintenance immunosuppressive regimen
      consisting of low-dose everolimus (EVR) in conjunction with low-dose cyclosporine
      (CsA) were compared to a matched cohort of 14 steroid-free patients on a standard
      dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose
      calcineurin inhibitor (CNI). The mean change in height standard deviation (SD)
      score in the first study year was 0.31 +/- 0.71 SD score in the EVR group
      compared to 0.31 +/- 0.64 SD score in the MMF group (P = 0.20). For the entire
      study period of 2 years, the change in height SD score in the EVR group was 0.43
      +/- 0.81 SDS compared to 0.75 +/- 0.85 SDS in the MMF group (P = 0.32). The
      percentage of prepubertal patients experiencing catch-up growth, defined as an
      increase in height SD score >=0.5 in 2 years, was similar in the EVR group (5/8,
      65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in
      steroid-free pediatric patients on low-dose EVR and CsA is not different to that
      of a matched steroid-free control group on an immunosuppressive regimen with
      standard-dose CNI and MMF. Hence, low-dose EVR does not appear to negatively
      impact short-term growth in pediatric renal transplant recipients.

PMID- 23865771
TI  - Fabrication of ceramic microspheres by diffusion-induced sol-gel reaction in
      double emulsions.
AB  - We demonstrate an approach to prepare zirconium dioxide (ZrO2) microspheres by
      carrying out a diffusion-induced sol-gel reaction inside double emulsion
      droplets. A glass capillary microfluidic device is introduced to generate
      monodisperse water-in-oil-in-water (W/O/W) double emulsions with a zirconium
      precursor as the inner phase. By adding ammonia to the continuous aqueous phase,
      the zirconium precursor solution is triggered to gel inside the emulsions. The
      double emulsion structure enhances the uniformity in the rate of the sol-gel
      reaction, resulting in sol-gel microspheres with improved size uniformity and
      sphericity. ZrO2 ceramic microspheres are formed following subsequent drying and
      sintering steps. Our approach, which combines double-emulsion-templating and sol
      gel synthesis, has great potential for fabricating versatile ceramic microspheres
      for applications under high temperature and pressure. 

PMID- 23865770
TI  - Maternal supportive and interfering control as predictors of adaptive and social
      development in children with and without developmental delays.
AB  - BACKGROUND: Parents of children with developmental delays (DD) have been found to
      use more controlling behaviour with their children than parents of children with
      typical development (TD). While controlling behaviour is related to poorer
      developmental outcomes in TD children, there is little research on how it
      predicts outcomes in DD children. Furthermore, existing research tends to use
      inconsistent or non-specific definitions of controlling behaviour, often
      combining parent control which follows the child's goal (e.g. supportive
      direction) and that which interferes with the child's goal (e.g. interference).
      METHODS: Participants were 200 mother-child dyads observed at child age 3, with
      follow-up assessments of adaptive behaviour and social skills administered at
      child ages 5 and 6, respectively. We coded the frequency of both types of
      controlling behaviour based on mothers' interactions with their children with TD
      (n = 113) or DD (n = 87) at age 3. RESULTS: Mothers in the DD group used more
      interfering but not more supportive directive acts compared to mothers in the TD
      group. Adaptive behaviour was assessed at child age 5 and social skills were
      assessed at age 6. Higher frequency of supportive directive acts predicted better
      adaptive functioning for the TD group and better social skills for the DD group.
      Higher frequency of interfering acts predicted lower adaptive and social skills
      for children with DD but not with TD. CONCLUSIONS: Results are discussed in terms
      of the differential developmental needs of children with and without DD as well
      as implications for early intervention.

PMID- 23865772
TI  - Defining natural species of bacteria: clear-cut genomic boundaries revealed by a
      turning point in nucleotide sequence divergence.
AB  - BACKGROUND: Bacteria are currently classified into arbitrary species, but whether
      they actually exist as discrete natural species was unclear. To reveal genomic
      features that may unambiguously group bacteria into discrete genetic clusters, we
      carried out systematic genomic comparisons among representative bacteria.
      RESULTS: We found that bacteria of Salmonella formed tight phylogenetic clusters
      separated by various genetic distances: whereas over 90% of the approximately
      four thousand shared genes had completely identical sequences among strains of
      the same lineage, the percentages dropped sharply to below 50% across the
      lineages, demonstrating the existence of clear-cut genetic boundaries by a steep
      turning point in nucleotide sequence divergence. Recombination assays supported
      the genetic boundary hypothesis, suggesting that genetic barriers had been formed
      between bacteria of even very closely related lineages. We found similar
      situations in bacteria of Yersinia and Staphylococcus. CONCLUSIONS: Bacteria are
      genetically isolated into discrete clusters equivalent to natural species.

PMID- 23865773
TI  - Comment on Sharma et al.: Closure of defunctioning loop ileostomy is associated
      with considerable morbidity.

PMID- 23865769
TI  - Pulmonary embolism and 3-month outcomes in 4036 patients with venous
      thromboembolism and chronic obstructive pulmonary disease: data from the RIETE
      registry.
AB  - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a
      modified clinical presentation of venous thromboembolism (VTE) but also a worse
      prognosis than non-COPD patients with VTE. As it may induce therapeutic
      modifications, we evaluated the influence of the initial VTE presentation on the
      3-month outcomes in COPD patients. METHODS: COPD patients included in the on
      going world-wide RIETE Registry were studied. The rate of pulmonary embolism
      (PE), major bleeding and death during the first 3 months in COPD patients were
      compared according to their initial clinical presentation (acute PE or deep vein
      thrombosis (DVT)). RESULTS: Of the 4036 COPD patients included, 2452 (61%; 95%
      CI: 59.2-62.3) initially presented with PE. PE as the first VTE recurrence
      occurred in 116 patients, major bleeding in 101 patients and mortality in 443
      patients (Fatal PE: first cause of death). Multivariate analysis confirmed that
      presenting with PE was associated with higher risk of VTE recurrence as PE (OR,
      2.04; 95% CI: 1.11-3.72) and higher risk of fatal PE (OR, 7.77; 95% CI: 2.92
      15.7). CONCLUSIONS: COPD patients presenting with PE have an increased risk for
      PE recurrences and fatal PE compared with those presenting with DVT alone. More
      efficient therapy is needed in this subtype of patients.

PMID- 23865774
TI  - Effects of the estrous cycle on the efficacy of oocyte collection and in vitro
      embryo production in Duroc-breed.
AB  - Collection efficacy and in vitro embryo developmental ability of oocytes obtained
      from Duroc-breed ovary donors at different stages of the estrous cycle (days 6,
      12 and 16 after estrus) were performed. The numbers of collected oocytes did not
      differ significantly among the different estrous cycle groups (total 72-90
      oocytes per gilt). However, the blastocyst rates of oocytes collected on days 12
      and 16 (9.2% and 19.4%, respectively) were significantly higher than those on day
      6 (1.1%). More oocytes were obtained on day 16 from small follicles (<2 mm in
      diameter; 85.3 oocytes per gilt) than from medium-sized (>=2-<6 mm) and large
      (>=6 mm) follicles (17.5 and 12.8 oocytes, respectively). The blastocyst rates in
      both the medium-sized and large follicle groups (20.0% and 19.2%, respectively)
      were significantly higher than that in the small follicle group (6.3%). The
      blastocyst cell numbers in both the medium-sized and large follicle groups (39.4
      and 43.3 cells, respectively) were significantly higher than that in the small
      follicle group (30.6 cells). The results suggest that oocyte collection from
      cycling Duroc pigs can be carried out efficiently from the late luteal to
      follicular stage. Those oocytes collected from medium-sized and large follicles
      show better embryo development. 

PMID- 23865775
TI  - Successful tolerance to fully MHC disparate renal allografts via donor
      hematopoietic mixed chimerism in non-human primates.

PMID- 23865776
TI  - Implementation of prehospital dispatch protocols that triage low-acuity patients
      to advice-line nurses.
AB  - INTRODUCTION: Although EMS agencies have been designed to efficiently provide
      medical assistance to individuals, the overuse of 9-1-1 as an alternative to
      primary medical care has resulted in the need for new methods to respond to this
      increasing demand. Our study analyzes the efficacy of classifying specific low
      acuity calls that can be transferred to an advice-line nurse for further medical
      instruction. The objectives of our study were to analyze the impact of
      implementing this protocol and resultant patient feedback regarding the transfer
      to an advice-line nurse. METHODS: We collected data for retrospective review from
      April 2011 to April 2012 from a single municipal EMS agency with an average
      annual call volume of approximately 90,000. Medical Priority Dispatch System
      response codes were assigned to calls based on patient acuity. Patients
      classified under Omega response codes were assessed for eligibility of transfer
      to nurse advice lines. Exclusion criteria included the following: if the call was
      placed by a third-party caller; if the patient refused to be transferred to the
      advice-line nurse; anytime the MPDS system was not used; if the patient was
      referred from a skilled nursing facility, school, or university nursing office,
      or physician's office. Telephone surveys were conducted for those patients who
      spoke to an advice-line nurse and did not receive an ambulance response 24 hours
      after calling 9-1-1 to obtain patient feedback. RESULTS: The database included
      1660 patients initially classified as Omega and eligible for transfer to an
      advice-line nurse. After applying the exclusion criteria, 329 (19.8%) patients
      were ultimately transferred to an advice-line nurse and 204 (12.3%) received no
      ambulance response. Of those patients who were not transported by ambulance 118
      (57.8%), patients completed telephone follow-up, with 104 (88.1%) reporting the
      nontransport option met their health-care needs and 108 (91.5%) responding they
      would accept the transfer again for a similar complaint. CONCLUSION: We
      identified an average of two patients per day as eligible for transfer to the
      nurse advice line, with less than one patient successfully completing the Omega
      protocol per day. While impact was limited, there was a decrease in ambulance
      response.

PMID- 23865777
TI  - Molecular characterization of hepatitis B virus in liver disease patients and
      asymptomatic carriers of the virus in Sudan.
AB  - BACKGROUND: Hepatitis B virus is hyperendemic in Sudan. Our aim was to
      molecularly characterize hepatitis B virus from Sudanese individuals, with and
      without liver disease, because genotypes play an important role in clinical
      manifestation and treatment management. METHODS: Ninety-nine patients - 30
      asymptomatic, 42 cirrhotic, 15 with hepatocellular carcinoma, 7 with acute
      hepatitis and 5 with chronic hepatitis- were enrolled. Sequencing of surface and
      basic core promoter/precore regions and complete genome were performed. RESULTS:
      The mean +/- standard deviation, age was 45.7+/-14.8 years and the male to female
      ratio 77:22. The median (interquartile range) of hepatitis B virus DNA and
      alanine aminotransferase levels were 2.8 (2.2-4.2) log IU/ml and 30 (19-49) IU/L,
      respectively. Using three genotyping methods, 81/99 (82%) could be genotyped.
      Forty eight percent of the 99 patients were infected with genotype D and 24% with
      genotype E, 2% with putative D/E recombinants and 7% with genotype A. Patients
      infected with genotype E had higher frequency of hepatitis B e antigen-positivity
      and higher viral loads compared to patients infected with genotype D. Basic core
      promoter/precore region mutations, including the G1896A in 37% of HBeAg-negative
      individuals, could account for hepatitis B e antigen-negativity. Pre-S deletion
      mutants were found in genotypes D and E. Three isolates had the vaccine escape
      mutant sM133T. CONCLUSION: Sudanese hepatitis B virus carriers were mainly
      infected with genotypes D or E, with patients infected with genotype E having
      higher HBeAg-positivity and higher viral loads. This is the first study to
      molecularly characterize hepatitis B virus from liver disease patients in Sudan.

PMID- 23865778
TI  - Antiproliferative activity of abietane diterpenoids against human tumor cells.
AB  - In the present study, the cytotoxicity of 30 diterpenoids with an abietane or a
      halimane skeleton was determined against five human tumor cell lines (HL-60,
      U937, Molt-3, SK-MEL-1, and MCF-7). Diterpenoids containing an abietane skeleton
      including taxodone (1) and taxodione (2), as well as the semisynthetic
      derivatives 12, 14, 15, 17, and 22, were the most cytotoxic compounds for human
      leukemia cells. Overexpression of the protective mitochondrial proteins Bcl-2 and
      Bcl-x(L) did not confer resistance to abietane diterpene-induced cytotoxicity.
      Studies performed on HL-60 cells indicated that growth inhibition triggered by
      compounds 1, 12, 14, and 15 was caused by induction of apoptosis. This was
      prevented by the nonspecific caspase inhibitor Z-VAD-FMK and, in the case of
      compounds 14 and 15, reduced by the selective caspase-8 inhibitor Z-IETD-FMK.
      Cell death induced by these abietane diterpenes was found to be associated with
      the release of mitochondrial proteins, including cytochrome c, Smac/DIABLO, and
      AIF (apoptosis-inducing factor), accompanied by dissipation of the mitochondrial
      membrane potential (DeltaPsi), and modulated by inhibition of extracellular
      signal-regulated kinases signaling and the p38 mitogen-activated protein kinase
      pathway.

PMID- 23865779
TI  - Life cycle assessment of representative swiss road pavements for national roads
      with an accompanying life cycle cost analysis.
AB  - The subject of this paper is an environmental life cycle assessment (LCA) and
      life cycle cost analysis (LCCA) of processes needed to construct and maintain
      representative Swiss asphalt, concrete, and composite pavements (including
      subbase layers) applicable for the Swiss national road network over a period of
      75 years. The environmental indicators analyzed are the global warming potential
      indicator, the nonrenewable cumulative energy demand, and the Swiss ecological
      scarcity indicator. Processes of the use phase of the road (fuel consumption,
      noise, etc.) have been evaluated qualitatively based on intensive research. The
      study shows that the global warming potential of concrete and asphalt pavements
      equilibrates over the analysis period and that concrete pavements compared to
      asphalt and composite pavements offer advantages in regards to the nonrenewable
      cumulative energy demand, the ecological scarcity indicator, and life cycle
      costs. The qualitative evaluation of the processes of the use phase shows for
      example the positive qualities of concrete pavements regarding fuel consumption
      and permanent noise properties. 

PMID- 23865780
TI  - Level alignment of a prototypical photocatalytic system: methanol on TiO2(110).
AB  - Photocatalytic activity depends on the optimal alignment of electronic levels at
      the molecule-semiconductor interface. Establishing the level alignment
      experimentally is complicated by the uncertain chemical identity of the surface
      species. We address the assignment of the occupied and empty electronic levels
      for the prototypical photocatalytic system consisting of methanol on a rutile
      TiO2(110) surface. Using many-body quasiparticle (QP) techniques, we show that
      the frontier levels measured in UV photoelectron and two-photon photoemission
      spectroscopy experiments can be assigned to molecularly chemisorbed methanol
      rather than its dissociated product, the methoxy species. We find that the
      highest occupied molecular orbital of the methoxy species is much closer to the
      valence band maximum, suggesting why it is more photocatalytically active than
      the methanol molecule. We develop a general semiquantitative model for predicting
      many-body QP energies based on the electronic screening within the bulk,
      molecular, or vacuum regions of the wave functions at molecule-semiconductor
      interfaces. 

PMID- 23865781
TI  - Fluxible nanoclusters of Fe3O4 nanocrystal-embedded polyaniline by macromolecule
      induced self-assembly.
AB  - We have prepared Fe3O4 nanocrystal-embedded polyaniline hybrids with well-defined
      cluster-like morphology through macromolecule-induced self-assembly. These
      magnetic and electrically conductive composite nanoclusters show flowability at
      room temperature in the absence of any solvent, which offers great potential in
      applications such as microwave absorbents and electromagnetic shielding coatings.
      This macromolecule-induced self-assembly strategy can be readily applied on the
      fabrication of other ion oxide/conjugated polymer composites to achieve robust
      multifunctional materials. 

PMID- 23865784
TI  - Ernie Mazzaferri.
AB  - NA.

PMID- 23865782
TI  - Allelic variation in two distinct Pseudomonas syringae flagellin epitopes
      modulates the strength of plant immune responses but not bacterial motility.
AB  - The bacterial flagellin (FliC) epitopes flg22 and flgII-28 are microbe-associated
      molecular patterns (MAMPs). Although flg22 is recognized by many plant species
      via the pattern recognition receptor FLS2, neither the flgII-28 receptor nor the
      extent of flgII-28 recognition by different plant families is known. Here, we
      tested the significance of flgII-28 as a MAMP and the importance of allelic
      diversity in flg22 and flgII-28 in plant-pathogen interactions using purified
      peptides and a Pseudomonas syringae ?fliC mutant complemented with different fliC
      alleles. The plant genotype and allelic diversity in flg22 and flgII-28 were
      found to significantly affect the plant immune response, but not bacterial
      motility. The recognition of flgII-28 is restricted to a number of solanaceous
      species. Although the flgII-28 peptide does not trigger any immune response in
      Arabidopsis, mutations in both flg22 and flgII-28 have FLS2-dependent effects on
      virulence. However, the expression of a tomato allele of FLS2 does not confer to
      Nicotiana benthamiana the ability to detect flgII-28, and tomato plants silenced
      for FLS2 are not altered in flgII-28 recognition. Therefore, MAMP diversification
      is an effective pathogen virulence strategy, and flgII-28 appears to be perceived
      by an as yet unidentified receptor in the Solanaceae, although it has an FLS2
      dependent virulence effect in Arabidopsis. 

PMID- 23865783
TI  - Is it acceptable for a physician to request informal payments for treatment? Lay
      people's and health professionals' views in Togo.
AB  - The people's views regarding informal payments for healthcare is essential if we
      are able to develop publicly supported interventions to address this phenomenon.
      We recruited a convenience sample of 300 lay people and health practitioners in
      Togo, a developing country experiencing this practice, and asked them how
      acceptable it would be for a physician to request informal payments for treatment
      in 36 scenarios. The scenarios were all combinations of three levels of the
      physician's income (relatively well-paid, average, or underpaid); two levels of
      the patient's wealth (wealthy vs. poor); two levels of the frequency of the
      practice in the area (common vs. rare); and three levels of the amount of payment
      requested ($50, $30, or $10). Two contrasting positions were found. A substantial
      minority of participants rejected the practice of informal payments, irrespective
      of circumstances. In contrast, a majority of them were of the opinion that when
      patients were wealthy and physicians were underpaid, this practice was
      acceptable. Health practitioners more frequently adhered to the ethical position
      than lay people. Implications for health policy are discussed. 

PMID- 23865785
TI  - Mutations in PDGFRB and NOTCH3 are the first genetic causes identified for
      autosomal dominant infantile myofibromatosis.

PMID- 23865787
TI  - Gynecologic cancer prevention and control in the National Comprehensive Cancer
      Control Program: progress, current activities, and future directions.
AB  - Gynecologic cancer confers a large burden among women in the United States.
      Several evidence-based interventions are available to reduce the incidence,
      morbidity, and mortality from these cancers. The National Comprehensive Cancer
      Control Program (NCCCP) is uniquely positioned to implement these interventions
      in the US population. This review discusses progress and future directions for
      the NCCCP in preventing and controlling gynecologic cancer.

PMID- 23865788
TI  - A critical evaluation of the evidence for ovarian conservation versus removal at
      the time of hysterectomy for benign disease.
AB  - BACKGROUND: Women undergoing hysterectomy for benign disease are presented with
      the choice of ovarian conservation or removal. The beneficial effect on ovarian
      cancer must be weighed against the risks of ovarian hormone withdrawal. Wide
      variations in practice patterns exist. METHODS: The purpose of this review
      article is to summarize and critically evaluate the existing primary evidence
      regarding the impact of adnexal conservation versus removal on the specific
      health issues of ovarian cancer, coronary heart disease (CHD), sexual and
      cognitive function, and osteoporotic hip fractures. RESULTS: Elective bilateral
      salpingo-oophorectomy (BSO) in women under 50 years is associated with an
      increased risk of CHD and sexual dysfunction. In women older than 50 years, there
      is no observed association between BSO and CHD, sexual dysfunction, osteoporotic
      hip fractures, or cognitive function. Oophorectomy is associated with a lower
      risk of death from ovarian cancer. CONCLUSION: Elective BSO should be discouraged
      in women under 50 years old. In postmenopausal women, however, BSO can reduce
      ovarian cancer rates without an adverse impact on CHD, sexual dysfunction, hip
      fractures, or cognitive function.

PMID- 23865786
TI  - Neo-adjuvant capecitabine chemotherapy in women with newly diagnosed locally
      advanced breast cancer in a resource-poor setting (Nigeria): efficacy and safety
      in a phase II feasibility study.
AB  - The majority of clinical trials of neo-adjuvant therapy for breast cancer have
      been conducted in resource-rich countries. We chose Nigeria, a resource-poor
      country, as the major site for a phase II feasibility open-label multicenter
      clinical trial designed to evaluate the efficacy, safety, and tolerability of neo
      adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment
      consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m(2) twice daily
      (2,000 mg/m(2) total per day). The primary endpoints were overall, partial,
      complete clinical response rate (OCR, PCR, CCR) and complete pathologic response
      (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The
      study was terminated early as a result of slow accrual. After the first three
      cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11-59%). Of
      the remaining 11 patients, eight had no response (NR) or stable disease (SD), and
      three had progressive disease (PD). Seven patients proceeded with further therapy
      of which had SD. OCR at the end of eight cycles was 44% (95% CI 20-70%). Clinical
      response and radiologic response by ultrasonomammography were highly concordant
      (spearman correlation 0.70). The most common adverse effect was Grade 1 hand-foot
      syndrome, which was seen in 75% of patients. Despite several limitations, we
      successfully carried out this phase II feasibility study of neo-adjuvant
      capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall
      response rates with minimal toxicity and further studies are warranted.

PMID- 23865789
TI  - Policies on worksite lactation support within states and organizations.
AB  - BACKGROUND: The issue of workplace lactation support has intensified due to the
      Affordable Care Act of 2010 (ACA) amendment of the Fair Labor Standards Act
      (FLSA) obliging employers to provide a reasonable break time for nursing mothers.
      OBJECTIVES: This objective of this study is to examine organizational policies on
      worksite lactation support as they relate to the new federal standards in state
      employees and within large state public and private universities. METHODS: State
      laws were collected from National Conference of State Legislators. Policies for
      state employees and large public and private universities were collected via
      human resource or personnel administration websites. The policies were coded for
      content and compared to FLSA requirements. The presence of state law on lactation
      support and extent to which the organizational policies encompass FSLA were
      compared with state breastfeeding rates at 6 months. RESULTS: After the ACA
      became effective in 2010, 33 state organizations, 36 state public universities,
      and 13 private universities issued the administrative notice and aligned their
      organizational policies with the federal requirements. Twenty-four states enacted
      worksite breastfeeding law prior to the 2010 federal law. Nineteen states with
      enacted worksite breastfeeding state laws also have lactation policies for state
      employees. CONCLUSION: States and universities vary in the presence of a formal,
      written lactation support policy for state employees. There was a significant
      correlation between State law and 6 months exclusive breastfeeding rates. Future
      research should investigate whether the federal law serves as stronger catalyst
      for organizational policies than does state law. Additionally, other policies
      such as paid maternity leave may also contribute to achieving the desired
      breastfeeding rates.

PMID- 23865791
TI  - YKL-40 and EGFR is a good biomarker for predicting nodal metastasis in anal
      carcinoma.

PMID- 23865790
TI  - Receptor for advanced glycation end products (RAGE) on iNKT cells mediates lung
      ischemia-reperfusion injury.
AB  - Activation of invariant natural killer T (iNKT) cells and signaling through
      receptor for advanced glycation end products (RAGE) are known to independently
      mediate lung ischemia-reperfusion (IR) injury. This study tests the hypothesis
      that activation of RAGE specifically on iNKT cells via alveolar macrophage
      produced high mobility group box 1 (HMGB1) is critical for the initiation of lung
      IR injury. A murine in vivo hilar clamp model was utilized, which demonstrated
      that RAGE(-/-) mice were significantly protected from IR injury. Treatment of WT
      mice with soluble RAGE (a decoy receptor), or anti-HMGB1 antibody, attenuated
      lung IR injury and inflammation, whereas treatment with recombinant HMGB1
      enhanced IR injury in WT mice but not RAGE(-/-) mice. Importantly, lung
      dysfunction, cytokine production and neutrophil infiltration were significantly
      attenuated after IR in Jalpha18(-/-) mice reconstituted with RAGE(-/-) iNKT cells
      (versus WT iNKT cells). In vitro studies demonstrated that, after hypoxia
      reoxygenation, alveolar macrophage-derived HMGB1 augmented IL-17 production from
      iNKT cells in a RAGE-dependent manner. These results suggest that HMGB1-mediated
      RAGE activation on iNKT cells is critical for initiation of lung IR injury and
      that a crosstalk between macrophages and iNKT cells via the HMGB1/RAGE axis
      mediates IL-17 production by iNKT cells causing neutrophil infiltration and lung
      IR injury.

PMID- 23865792
TI  - Calcaripeptides A-C, cyclodepsipeptides from a Calcarisporium strain.
AB  - The isolation and structure elucidation of the novel calcaripeptides A (1), B
      (2), and C (3) and studies on their biosynthetic origin are described. The
      calcaripeptides were identified from Calcarisporium sp. strain KF525, which was
      isolated from the German Wadden Sea. Compounds 1-3 are macrocyclic structures
      composed of a proline and a phenylalanine residue as well as a nonpeptidic
      substructure. Structure elucidation was achieved by applying one- and two
      dimensional NMR spectroscopy supported by high-resolution mass spectrometry. X
      ray crystallography was performed to determine the relative configuration of 1.
      The absolute configuration of 1 was assigned by HPLC of the amino acids after
      hydrolysis of the molecule and derivatization with chiral agents. Studies on the
      biosynthesis by feeding 13C-labeled substrates revealed that the nonpeptidic part
      of 1 originates from acetate and l-methionine. The involvement of a hybrid
      between a polyketide synthase and a nonribosomal peptide synthetase in the
      biosynthesis of the calcaripeptides is discussed.

PMID- 23865793
TI  - Development and characterization of stable nanovesicular carrier for drug
      delivery.
AB  - Lipid vesicles are an important drug carrier which can serve for controlled
      delivery of drugs; however, these vesicles are quite unstable at ambient
      temperature and require stringent storage condition. Present work was done to
      develop a stable vesicular system for drug delivery. Vesicles of ceramide-2,
      cholesterol, cholesterol sulfate, and palmitic acid were prepared and compared
      with phosphatidylcholine vesicles for physicochemical parameters and accelerated
      stability. Diclofenac sodium was used as a model drug. Based on physicochemical
      parameter and in vitro release PCV-3 and CV-3 were selected for further studies
      in three different accelerated stability conditions. PCV-3 showed moderate
      changes at 4 degrees C but was severely affected at 25 degrees C and 40 degrees
      C. CV-3 showed stable characteristics at 4 degrees C and 25 degrees C whereas at
      40 degrees C, CV-3 showed signs of slight modification owing to moisture
      absorption. Based on the study, CV-3 containing highest content of palmitic acid
      was found to be most stable.

PMID- 23865794
TI  - Zest for life among 65- and 75-year-olds in Northern Finland and Sweden--a cross
      sectional study.
AB  - BACKGROUND: Zest for life refers to being satisfied with life and having the
      energy and courage to look for new experiences. Research into zest for life among
      older people is scarce, even though it is an important topic. Similarly related
      concepts such as life satisfaction, quality of life and purpose in life have
      received more attention. AIM: The aim of this study was to investigate zest for
      life and factors and variables associated with zest for life among 65- and 75
      year-olds. METHOD: A descriptive cross-sectional design was used, employing data
      from a cross-sectional survey in Northern Finland and Sweden with a total of 3372
      respondents. Sociodemographic data were gathered: social contacts; helping
      relatives; activities; involvement in society; health; use of social services;
      economic situation; ageism; crises in life; and well-being. Logistic regression
      analysis was employed to examine independent factors associated with zest for
      life. RESULTS: A total of 2854 respondents (nearly 85%) reported having zest for
      life, with only 47 (1.4%) having no zest for life. Several factors were
      significantly associated with zest for life. Using logistic regression analysis,
      the following factors were found to be determinants of zest for life: no diseases
      (OR = 9.1), general health (OR = 6.1), not discriminated against due to age (OR =
      5.4), no crises in life last year (OR = 7.0), experienced depression never/seldom
      (OR = 88.4) and experienced meaning in life (OR = 10.4). CONCLUSIONS: In general,
      65- and 75-year-olds in Finland and Sweden have a zest for life. Even though the
      study sample shows that only a small number of respondents have no zest for life,
      zest for life is a concept worth investigating in that there exists a strong
      association between no zest for life and depression. Physical and psychological
      health and well-being are important determinates of zest for life and, seemingly,
      a determinate for successful ageing.

PMID- 23865795
TI  - Rheological study of chitosan/polyol-phosphate systems: influence of the polyol
      part on the thermo-induced gelation mechanism.
AB  - Thermo-sensitive gelling systems, like chitosan/polyol-phosphate, are candidates
      with a high potential for the design of biodegradable drug delivery systems,
      notably for in situ forming depots. They consist of stable and low viscosity
      aqueous solutions, liquid at room temperature, which turn into a gel state upon
      an increase of temperature (e.g., after subcutaneous administration). This
      technology enables a sustained release of potentially encapsulated active
      substances. Despite these thermo-gelling solutions being widely studied for the
      development of parenteral drug delivery systems, most commonly using beta
      glycerophosphate (beta-GP) as gelling agent, the mechanism inducing the gelation
      and the role of the polyol part in this mechanism has not been clearly
      elucidated. To investigate the mechanism of the gelation process, comprehensive
      rheological studies were performed, comparing different chitosan/polyol-phosphate
      systems varying in the chemical structure of the polyol parts of the gelling
      agents. As reference, beta-GP was compared to glucose-1-phosphate (G1-P) and
      glucose-6-phosphate (G6-P) and to a polyol-free phosphate salt, Na2HPO4, as well.
      Frequency sweep experiments at different temperatures or different gelling agent
      concentrations, temperature, and time sweep tests were performed as complementary
      experimental approaches. The results disclosed significant trends with widespread
      implications, establishing a relationship between the chemical structure of the
      polyol part and the macroscopic gelling behavior of the solutions, that is,
      transition temperature, gelation time, and gel strength. The new results
      presented in this study show that increasing the size of the polyol part prevents
      the interactions between the chitosan chains, strongly influencing the gelling
      process. 

PMID- 23865797
TI  - Dietary pattern analysis and biomarkers of low-grade inflammation: a systematic
      literature review.
AB  - The purpose of the present literature review was to investigate and summarize the
      current evidence on associations between dietary patterns and biomarkers of
      inflammation, as derived from epidemiological studies. A systematic literature
      search was conducted using PubMed, Web of Science, and EMBASE, and a total of 46
      studies were included in the review. These studies predominantly applied
      principal component analysis, factor analysis, reduced rank regression analysis,
      the Healthy Eating Index, or the Mediterranean Diet Score. No prospective
      observational study was found. Patterns identified by reduced rank regression as
      being statistically significantly associated with biomarkers of inflammation were
      almost all meat-based or "Western" patterns. Studies using principal component
      analysis or a priori-defined diet scores found that meat-based or "Western-like"
      patterns tended to be positively associated with biomarkers of inflammation,
      predominantly C-reactive protein, while vegetable- and fruit-based or "healthy"
      patterns tended to be inversely associated. While results of the studies were
      inconsistent, interventions with presumed healthy diets resulted in reductions of
      almost all investigated inflammatory biomarkers. In conclusion, prospective
      studies are warranted to confirm the reported findings and further analyze
      associations, particularly by investigating dietary patterns as risk factors for
      changes in inflammatory markers over time. 

PMID- 23865796
TI  - Beyond the Paleolithic prescription: incorporating diversity and flexibility in
      the study of human diet evolution.
AB  - Evolutionary paradigms of human health and nutrition center on the evolutionary
      discordance or "mismatch" model in which human bodies, reflecting adaptations
      established in the Paleolithic era, are ill-suited to modern industrialized
      diets, resulting in rapidly increasing rates of chronic metabolic disease. Though
      this model remains useful, its utility in explaining the evolution of human
      dietary tendencies is limited. The assumption that human diets are mismatched to
      the evolved biology of humans implies that the human diet is instinctual or
      genetically determined and rooted in the Paleolithic era. This review looks at
      current research indicating that human eating habits are learned primarily
      through behavioral, social, and physiological mechanisms that start in utero and
      extend throughout the life course. Adaptations that appear to be strongly genetic
      likely reflect Neolithic, rather than Paleolithic, adaptations and are
      significantly influenced by human niche-constructing behavior. Several examples
      are used to conclude that incorporating a broader understanding of both the
      evolved mechanisms by which humans learn and imprint eating habits and the
      reciprocal effects of those habits on physiology would provide useful tools for
      structuring more lasting nutrition interventions. 

PMID- 23865799
TI  - Ghrelin, neuropeptide Y, and other feeding-regulatory peptides active in the
      hippocampus: role in learning and memory.
AB  - The hippocampus is a brain region of primary importance for neurogenesis, which
      occurs during early developmental states as well as during adulthood. Increases
      in neuronal proliferation and in neuronal death with age have been associated
      with drastic changes in memory and learning. Numerous neurotransmitters are
      involved in these processes, and some neuropeptides that mediate neurogenesis
      also modulate feeding behavior. Concomitantly, feeding peptides, which act
      primarily in the hypothalamus, are also present in the hippocampus. This review
      aims to ascertain the role of several important feeding peptides in cognitive
      functions, either through their local synthesis in the hippocampus or through
      their actions via specific receptors in the hippocampus. A link between
      neurogenesis and the orexigenic or anorexigenic properties of feeding peptides is
      discussed. 

PMID- 23865798
TI  - Influence of iron status on risk of maternal or neonatal infection and on
      neonatal mortality with an emphasis on developing countries.
AB  - Infection is a major cause of neonatal death in developing countries. This review
      investigates whether host iron status affects the risk of maternal and/or
      neonatal infection, potentially contributing to neonatal death, and summarizes
      the iron acquisition mechanisms described for pathogens causing stillbirth,
      preterm birth, and congenital infection. In vitro evidence shows that iron
      availability influences the severity and chronicity of infections that cause
      these negative outcomes of pregnancy. In vivo evidence is lacking, as relevant
      studies of maternal iron supplementation have not assessed the effect of iron
      status on the risk of maternal and/or neonatal infection. Reducing iron
      deficiency anemia among women is beneficial and should improve the iron stores of
      babies; moreover, there is evidence that iron status in young children predicts
      the risk of malaria and, possibly, the risk of invasive bacterial diseases.
      Caution with maternal iron supplementation is indicated in iron-replete women who
      may be at high risk of exposure to infection, although distinguishing between
      iron-replete and iron-deficient women is currently difficult in developing
      countries, where a point-of-care test is needed. Further research is indicated to
      investigate the risk of infection relative to iron status in mothers and babies
      in order to avoid iron intervention strategies that may result in detrimental
      birth outcomes in some groups of women. 

PMID- 23865800
TI  - Pleiotropic effects of genistein in metabolic, inflammatory, and malignant
      diseases.
AB  - Genistein is a soy-derived biologically active isoflavone that exhibits diverse
      health-promoting effects. An increasing body of evidence shows that genistein
      influences lipid homeostasis and insulin resistance, counteracts inflammatory
      cytokines, and possesses antidiabetic properties. Genistein also impedes cancer
      progression by promoting apoptosis, inducing cell cycle arrest, modulating
      intracellular signaling pathways, and inhibiting angiogenesis and metastasis of
      neoplastic cells. This review summarizes the pleiotropic functions of genistein
      in common health disorders such as metabolic syndrome, chronic inflammatory
      diseases, and cancer. In the current era of uncontrolled health expenditure, a
      focus on the clinical development of nutritional agents with the capacity to
      prevent a variety of common health disorders is needed. As a micronutrient that
      exerts multifaceted effects ranging from antidiabetic to anticarcinogenic
      functions, genistein should be clinically developed further for use in the
      prevention and treatment of a variety of health disorders. 

PMID- 23865801
TI  - Energy transfer pathways in light-harvesting complexes of purple bacteria as
      revealed by global kinetic analysis of two-dimensional transient spectra.
AB  - Excited state dynamics in LH2 complexes of two purple bacterial species were
      studied by broad-band two-dimensional electronic spectroscopy. The optical
      response was measured in the 500-600 nm spectral region on the 0-400 fs time
      scale. Global target analysis of two-dimensional (2D) transient spectra revealed
      the main energy transfer pathways between carotenoid S2, 1Bu(-) and S1 states and
      bacteriochlorophyll Qx state. Global analysis ascertained the evolutionary and
      vibration-associated spectra, which also indicated the presence of a higher-lying
      vibrational level in the carotenoid S1 state. The estimation of the spectral
      overlap between the 1Bu(-) state and the Qx state indicated a significant
      contribution of the 1Bu(-) state to the overall S2-to-Qx excitation energy
      transfer. 

PMID- 23865802
TI  - Outcomes in young adulthood: are we achieving community participation and
      inclusion?
AB  - BACKGROUND: Despite recognition of the importance of integrated community living
      and support, there is evidence that parents remain the primary caregivers of
      young adults with intellectual disability (ID). In addition, employment rates
      remain low in this population. This study aimed to investigate the changes in
      living arrangements and participation in daytime activities over time in a
      community population of young people with ID. METHOD: The sample consisted of 536
      participants aged 4.0-18.9 years at Wave 1, followed up at Wave 5 when aged 20.5
      37.6 years. Information was collected on their living arrangements and daytime
      activities at both time points, along with living skills and information on
      community social inclusion at Wave 5. For parents still caring for their adult
      child with ID, information was also collected on parental ratings of their own
      mental and physical health, and their satisfaction with the long-term care
      arrangements for their adult child. RESULTS: A significant proportion of young
      people were still living with their parents at Wave 5. A greater proportion of
      those with a severe-profound degree of ID were living in residential care.
      Parents caring for their adult child reported high levels of mental health
      problems and dissatisfaction with the long-term care arrangements for their
      child. A small proportion of young people were in paid employment, and the
      majority was engaged in structured activities provided for those with an ID. Over
      one-third of the sample participated in a structured daytime activity for 10 or
      fewer hours per week, and 7% were not engaged in any structured daytime activity.
      CONCLUSIONS: These results suggest that adequate provision of accommodation and
      employment services for young adults with an ID is lacking. In many cases the
      responsibility of care continues to reside with parents as their children
      transition from childhood to adulthood. Greater attention is needed to address
      these issues and facilitate social inclusion and integration for young people
      with ID.

PMID- 23865803
TI  - Sentinel lymph node biopsy for risk-reducing mastectomy.
AB  - Risk-reducing mastectomy (RRM) confers 90-95% decreased risk of breast cancer,
      and may reduce mortality, especially in high-risk groups such as BRCA carriers.
      Risk of occult disease in RRM specimen is ~5%. This demands axillary staging:
      sentinel lymph node (SLN) biopsy is no longer possible, axillary clearance
      confers significant risks and may prove negative. Contemporaneous SLN biopsy
      allows axillary staging with minimal further dissection. Women undergoing RRM and
      SLN biopsy between June 2005 and July 2010 were reviewed retrospectively from our
      prospectively maintained database of 1,522 SLN procedures in 1,498 patients.
      SLN(s) localized using routine tracer methods. SLNs and mastectomy specimens
      underwent routine histologic examination. Eighty-three RRMs with SLN biopsy were
      performed in 71 patients (12 bilateral). Indications for RRM: contralateral
      invasive (55), in situ (5) disease, BRCA 1/2 mutation (12), and strong family
      history (10). Mean number of SLNs: 1.35. Occult disease was detected in four
      cases (4.8%), with one case of occult invasive lobular carcinoma (1.2%).
      Remaining occult disease was lobular in situ neoplasia (LISN). SLNs were negative
      in all cases. Our findings are comparable to those in the literature: 4.8% rate
      of occult disease overall, 1.2% invasive. The significant risk with SLN biopsy is
      lymphoedema, quoted around 7%. We have had no reports of symptomatic lymphoedema
      in patients undergoing RRM and SLN biopsy. We propose that SLN at the time of
      mastectomy requires only limited further dissection, and confers minimal risk
      compared with secondary axillary surgery. 

PMID- 23865804
TI  - Retrospective analysis of the success and safety of Gold Micro Shunt Implantation
      in glaucoma.
AB  - BACKGROUND: To evaluate the success rate and adverse effects of Gold Micro Shunt
      Plus (GMS+) implantation into the supraciliary space. METHODS: This retrospective
      study included 31 eyes of 31 patients diagnosed with severe glaucoma and
      uncontrolled intraocular pressure (IOP) with implantation of a GMS+ by means of a
      full-thickness scleral flap. The main outcome measures were surgical failure or
      success, based on the intraocular pressure and adverse effects. Clinical
      examination data are reported up to 4 years postoperatively. RESULTS: Thirty eyes
      (97%) met one of our criteria for failure. Within a mean of 7.3 +/- 7.7 months
      another surgery was performed because of elevated IOP in 24 of 31 eyes (77%) and
      because of adverse effects in 2 (6%). The remaining 4 eyes, that met one of our
      criteria for failure, had an IOP reduction of less than 20% with comparable
      medication. Six GMS+'s were explanted; because of IOP elevation, 2; rubeosis
      iridis, 2; and low grade inflammation, 2. CONCLUSIONS: GMS+ implantation is not
      an effective method to control IOP in patients with glaucoma, when using our
      surgical technique. The reason for the found signs of chronic low grade
      inflammation or rubeosis iridis in 4 eyes (13%) remains unknown and has to be
      further investigated.

PMID- 23865805
TI  - Characterising the aetiology of severe acute gastroenteritis among patients
      visiting a hospital in Qatar using real-time polymerase chain reaction.
AB  - BACKGROUND: Acute gastroenteritis (AGE) remains a common cause of clinic visits
      and hospitalizations, though its aetiology has not been determined in Qatar.
      METHODS: We performed a prospective, emergency department-based study of 288
      children and adults with AGE. Stool specimens were collected at presentation from
      June to November 2009. Faecal specimens were tested, using real-time PCR, for a
      panel of four viral (norovirus, adenovirus, astrovirus and rotavirus) and
      bacterial pathogens. RESULTS: Viral and bacterial pathogens were detected in 131
      (45.5%) and 34 (12.2%) of the 288 patients recruited. The most commonly detected
      pathogens were norovirus (28.5%), rotavirus (10.4%), followed by adenovirus
      (6.25%) and astrovirus (0.30%). Norovirus was the most commonly detected viral
      pathogen amongst all the age groups with an almost even distribution in all age
      groups. Rotavirus and adenovirus were more common in children under 5 yr of age.
      Astrovirus was found in only one person. CONCLUSIONS: Viruses, especially
      noroviruses, are associated with severe diarrhoea in children and adults in
      Qatar. Further studies to confirm the findings and to explore the causes of
      illness among patients from whom a pathogen cannot be determined are needed.

PMID- 23865806
TI  - Short-term outcomes of US Air Force Critical Care Air Transport Team (CCATT)
      patients evacuated from a combat setting.
AB  - PURPOSE: The purpose of this study is to describe the short-term outcomes (during
      air transport) of patients managed by the United States Air Force Critical Care
      Air Transport Teams (CCATT). METHODS: This is a retrospective chart review of
      patients who were transported by CCATT between March 1, 2007 and June 30, 2008. A
      standardized abstraction form was used. Patients were classified as medical or
      trauma. Care given inflight was documented, including mechanical ventilation,
      vasoactive medication administration, and administration of blood products. Short
      term events (during air transport) included death, oxyhemoglobin desaturation,
      hypotension, decline in neurological status, development of anuria or oliguria,
      and dislodgement of endotracheal and chest tubes. RESULTS: A total of 656 patient
      moves met inclusion criteria, of which 425 (64.8%) were trauma and 231 (35.2%)
      were medical. Mechanical ventilation was required by 318 (49%), 68 (10%) received
      vasoactive medications, and 43 (7%) required blood products during the flight.
      There were a total of 75 events documented on 65 patient transports (10%). Of
      these, 19 were oxyhemoglobin desaturation, 29 were hypotension, 3 were decline in
      neurological status, and 23 were due to anuria or oliguria. We did not encounter
      any deaths or loss of airway or chest tubes during transport. CONCLUSION: CCATTs
      are a successful platform in transporting critically injured/ill patients with
      minimal short-term complications.

PMID- 23865808
TI  - The timing of TGF-beta inhibition affects the generation of antigen-specific CD8+
      T cells.
AB  - BACKGROUND: Transforming growth factor (TGF)-beta is a potent immunosuppressive
      cytokine necessary for cancer growth. Animal and human studies have shown that
      pharmacologic inhibition of TGF-beta slows the growth rate of established tumors
      and occasionally eradicates them altogether. We observed, paradoxically, that
      inhibiting TGF-beta before exposing animals to tumor cells increases tumor growth
      kinetics. We hypothesized that TGF-beta is necessary for the anti-tumor effects
      of cytotoxic CD8+ T lymphocytes (CTLs) during the early stages of tumor
      initiation. METHODS: BALB/c mice were pretreated with a blocking soluble TGF-beta
      receptor (sTGF-betaR, TGF-beta-blockade group, n=20) or IgG2a (Control group,
      n=20) before tumor inoculation. Tumor size was followed for 6 weeks. In vivo
      lymphocyte assays and depletion experiments were then performed to investigate
      the immunological basis of our results. Lastly, animals were pretreated with
      either sTGF-betaR (n=6) or IgG2a (n=6) prior to immunization with an adenoviral
      vector encoding the human papillomavirus E7 gene (Ad.E7). One week later, flow
      cytometry was utilized to measure the number of splenic E7-specific CD8+ T cells.
      RESULTS: Inhibition of TGF-beta before the injection of tumor cells resulted in
      significantly larger average tumor volumes on days 11, 17, 22, 26 and 32 post
      tumor-inoculation (p < 0.05). This effect was due to the inhibition of CTLs, as
      it was not present in mice with severe combined immunodeficiency (SCID) or those
      depleted of CD8+ T cells. Furthermore, pretreatment with sTGF-betaR inhibited
      tumor-specific CTL activity in a Winn Assay. Tumors grew to a much larger size
      when mixed with CD8+ T cells from mice pretreated with sTGF-betaR than when mixed
      with CD8+ T cells from mice in the control group: 96 mm3 vs. 22.5 mm3,
      respectively (p < 0.05). In addition, fewer CD8+ T cells were generated in Ad.E7
      immunized mice pretreated with sTGF-betaR than in mice from the control group:
      0.6% total CD8+ T cells vs. 1.9%, respectively (p < 0.05). CONCLUSIONS: These
      studies provide the first in vivo evidence that TGF-beta may be necessary for
      anti-tumor immune responses in certain cancers. This finding has important
      implications for our understanding of anti-tumor immune responses, the role of
      TGF-beta in the immune system, and the future development of TGF-beta inhibiting
      drugs.

PMID- 23865807
TI  - Competition between homodimerization and cholesterol binding to the C99 domain of
      the amyloid precursor protein.
AB  - The 99-residue transmembrane C-terminal domain (C99, also known as beta-CTF) of
      the amyloid precursor protein (APP) is the product of the beta-secretase cleavage
      of the full-length APP and is the substrate for gamma-secretase cleavage. The
      latter cleavage releases the amyloid-beta polypeptides that are closely
      associated with Alzheimer's disease. C99 is thought to form homodimers; however,
      the free energy in favor of dimerization has not previously been quantitated. It
      was also recently documented that cholesterol forms a 1:1 complex with monomeric
      C99 in bicelles. Here, the affinities for both homodimerization and cholesterol
      binding to C99 were measured in bilayered lipid vesicles using both electron
      paramagnetic resonance (EPR) and Forster resonance energy transfer (FRET)
      methods. Homodimerization and cholesterol binding were seen to be competitive
      processes that center on the transmembrane G700XXXG704XXXG708 glycine-zipper
      motif and adjacent Gly709. On one hand, the observed Kd for cholesterol binding
      (Kd = 2.7 +/- 0.3 mol %) is on the low end of the physiological cholesterol
      concentration range in mammalian cell membranes. On the other hand, the observed
      K(d) for homodimerization (K(d) = 0.47 +/- 0.15 mol %) likely exceeds the
      physiological concentration range for C99. These results suggest that the 1:1
      cholesterol/C99 complex will be more highly populated than C99 homodimers under
      most physiological conditions. These observations are of relevance for
      understanding the gamma-secretase cleavage of C99.

PMID- 23865809
TI  - Monitoring translation with modified mRNAs strategically labeled with isomorphic
      fluorescent guanosine mimetics.
AB  - Here we examine three mRNAs, site-specifically modified at codon positions 4, 5,
      and 6 with a new emissive and responsive isosteric guanosine mimetic ((th)G),
      with the goal of developing real time assays for monitoring translation-related
      events at nucleotide resolution. All three emissive mRNAs tested form initiation
      (70SIC), pretranslocation (PRE), and posttranslocation (POST) complexes. In most
      cases spectral differences are seen on binding of the mRNA to the ribosome during
      70SIC formation and on conversion of 70SIC to PRE complexes and PRE complexes to
      POST complexes. These differences allow measurement of the kinetics of such
      conversions by changes in the fluorescence of labeled mRNAs. Such measurements
      directly identify a specific step during PRE complex formation, provisionally
      assigned to codon:anticodon-loop base pair formation, that follows aa-tRNA.EF
      Tu.GTP ternary complex binding to the ribosome and precedes aa-tRNA accommodation
      into the A-site of the ribosome. These observations demonstrate not only the
      functionality of mRNAs modified with the emissive guanosine mimetic but also the
      potential this mimetic offers for observing the formation and disappearance of
      discrete intermediates during the polypeptide elongation cycle. 

PMID- 23865810
TI  - Fast online and index-based algorithms for approximate search of RNA sequence
      structure patterns.
AB  - BACKGROUND: It is well known that the search for homologous RNAs is more
      effective if both sequence and structure information is incorporated into the
      search. However, current tools for searching with RNA sequence-structure patterns
      cannot fully handle mutations occurring on both these levels or are simply not
      fast enough for searching large sequence databases because of the high
      computational costs of the underlying sequence-structure alignment problem.
      RESULTS: We present new fast index-based and online algorithms for approximate
      matching of RNA sequence-structure patterns supporting a full set of edit
      operations on single bases and base pairs. Our methods efficiently compute semi
      global alignments of structural RNA patterns and substrings of the target
      sequence whose costs satisfy a user-defined sequence-structure edit distance
      threshold. For this purpose, we introduce a new computing scheme to optimally
      reuse the entries of the required dynamic programming matrices for all substrings
      and combine it with a technique for avoiding the alignment computation of non
      matching substrings. Our new index-based methods exploit suffix arrays
      preprocessed from the target database and achieve running times that are
      sublinear in the size of the searched sequences. To support the description of
      RNA molecules that fold into complex secondary structures with multiple ordered
      sequence-structure patterns, we use fast algorithms for the local or global
      chaining of approximate sequence-structure pattern matches. The chaining step
      removes spurious matches from the set of intermediate results, in particular of
      patterns with little specificity. In benchmark experiments on the Rfam database,
      our improved online algorithm is faster than the best previous method by up to
      factor 45. Our best new index-based algorithm achieves a speedup of factor 560.
      CONCLUSIONS: The presented methods achieve considerable speedups compared to the
      best previous method. This, together with the expected sublinear running time of
      the presented index-based algorithms, allows for the first time approximate
      matching of RNA sequence-structure patterns in large sequence databases. Beyond
      the algorithmic contributions, we provide with RaligNAtor a robust and well
      documented open-source software package implementing the algorithms presented in
      this manuscript. The RaligNAtor software is available at http://www.zbh.uni
      hamburg.de/ralignator.

PMID- 23865811
TI  - Relationship between Internet use and general belief in a just world among
      Chinese retirees.
AB  - As an emerging medium for acquiring information, the Internet might affect how
      users, including older adults, view or think about the world around them. Using
      data from a survey of retirees aged 50 years and above (N=12,309) in China, the
      present study examined the relationship between Internet use for acquiring
      information about the world and general belief in a just world (GBJW). The
      results indicated that Internet use primarily for obtaining news information was
      negatively related to GBJW. Specifically, Internet users had lower levels of GBJW
      than nonusers; the more time retirees spent visiting Web sites to acquire news
      information, the less likely they were to believe that the world is just. In
      addition, compared with retirees who had acquired information about the world
      through other means (including books, newspapers or magazines, radio and
      television, and direct communication with other people), those who had acquired
      information primarily using the Internet showed lower levels of GBJW. The
      significance and limitations of the current study are discussed.

PMID- 23865813
TI  - Application of FORDISC 3.0 to explore differences among crania of North American
      and South African blacks and whites.
AB  - Using discriminant function analysis, classification accuracies for ancestry and
      sex in white and black South Africans were compared using North American (FDB),
      African groups in Howells (HDB), and South African (SADB) databases in FORDISC
      3.0. (FD3). Twenty-four standard linear measures were collected from a total of
      86 black and 101 white crania obtained from the Pretoria Bone Collection. White
      and black South Africans classified 73% correctly in FDB, 55% correctly in HDB,
      and 71% correctly in SADB. The percentage of atypical cases was higher with FDB
      than SADB. In all three databases, misclassification occurred more with sex than
      ancestry revealing differences in sexual dimorphism between population groups.
      Broad ancestral differences may explain low misclassification rates for ancestry.
      FD3, with a modern South African reference sample, can assist South African
      anthropologists to standardize methodology and to justify procedures for
      estimating ancestry.

PMID- 23865814
TI  - Caregiver perspectives on cancer screening for persons with dementia: "why put
      them through it?".
AB  - OBJECTIVES: To describe the perspectives of family caregivers toward stopping
      cancer screening tests for their relatives with dementia and identify
      opportunities to reduce harmful or unnecessary screening. DESIGN: Focus group
      study. SETTING: Alzheimer's Association support groups for family members of
      individuals with dementia. PARTICIPANTS: Four focus groups including 32
      caregivers (25 female; 24 white, 7 African American, one American/Indian; mean
      age 65.5, range 49-85). MEASUREMENTS: Focus group transcripts were transcribed
      and analyzed using methods of grounded theory. RESULTS: Caregivers considered
      decisions to stop cancer screening in terms of quality of life and burden on the
      patient and caregiver. Many described having to intervene in the patient's care
      to stop unnecessary or harmful screening, and others met resistance when they
      advocated for stopping. Physicians varied widely in their knowledge of dementia
      care and willingness to consider cessation of screening. CONCLUSION: Many family
      caregivers wish to stop cancer screening tests as dementia progresses and are
      relieved when physicians bring it up. Caregivers are open to discussions of
      screening cessation that focus on quality of life, burdens, and benefits.
      Interventions are needed to increase caregiver and clinician discussion of
      screening cessation and to increase clinician awareness of the need to reconsider
      cancer screening in individuals with dementia.

PMID- 23865815
TI  - Differences in serial lung function recorded on four data-logging meters.
AB  - OBJECTIVE: Lung function measurements performed several times daily are useful
      for the diagnosis of occupational asthma. Patient fabrication of hand-recorded
      charts can limit confidence in the results; this is overcome using electronic
      meters that log time and measurement. We have compared individual and meter
      differences in FEV1 and PEF recorded by hand and from meter logs using expert
      subjects on four data-logging spirometers with different methods of measurement
      and different quality control software. METHODS: Eight workers in a respiratory
      physiology department were asked to record FEV1 and PEF 2-hourly from waking for
      7 days using four electronic meters (Easyone, Micro DL, Vitalograph Diary card
      2110 and Piko-1) in random order. Subjects hand-recorded the best FEV1 and PEF
      from each session, this was compared with the logged data. RESULTS: Discordant
      measurements from individuals were lower for FEV1 than PEF and differed from 4.4
      19.1% for FEV1 (mean 9.4%, p < 0.0001) and 6-23.3% for PEF (mean 12.6, p <
      0.0001). There were also significant differences between meters for both
      variables (p < 0.0001). The magnitude of the differences in PEF was highest for
      the Easyone (34l/min) and lowest for the Vitalograph Diary card 2110 (14l/min)
      and varied significantly between meters (mean 22l/min, p = 0.002). CONCLUSIONS:
      Differences between hand-recorded and logged measurements are unlikely to be due
      solely to patient fabrication and can be due to quality criteria or other unclear
      software requirements applied after the results are shown on the meter screen;
      they differ between meters. Whether the differences shown affect clinical outcome
      will require further investigation.

PMID- 23865816
TI  - A synthetic zipper peptide motif orchestrated via co-operative interplay of
      hydrogen bonding, aromatic stacking, and backbone chirality.
AB  - Here, we report on a new class of synthetic zipper peptide which assumes its
      three-dimensional zipper-like structure via a co-operative interplay of hydrogen
      bonding, aromatic stacking, and backbone chirality. Structural studies carried
      out in both solid- and solution-state confirmed the zipper-like structural
      architecture assumed by the synthetic peptide which makes use of unusually remote
      inter-residual hydrogen-bonding and aromatic stacking interactions to attain its
      shape. The effect of chirality modulation and the extent of noncovalent forces in
      the structure stabilization have also been comprehensively explored via single
      crystal X-ray diffraction and solution-state NMR studies. The results highlight
      the utility of noncovalent forces in engineering complex synthetic molecules with
      intriguing structural architectures. 

PMID- 23865817
TI  - Edwardsiellosis caused by Edwardsiella ictaluri in laboratory populations of
      Zebrafish Danio rerio.
AB  - We report the first cases of Edwardsiella ictaluri causing epizootics in
      laboratory populations of Zebrafish Danio rerio. Edwardsiella ictaluri is
      primarily recognized as a disease of catfish species and is known to cause an
      economically important bacterial disease of farm-raised catfish in the USA and
      abroad; however, it has been isolated on occasion from 10 other genera of
      nonictalurid fishes. We isolated E. ictaluri from moribund Zebrafish held in
      quarantine at two different universities in two states and from a research
      facility in a third state between February 23 and December 6, 2011.
      Edwardsiellosis in Zebrafish can be described as a severe systemic disease
      characterized by tissue necrosis and the presence of large numbers of
      extracellular and intracellular bacteria, often within macrophages. The kidneys
      (pronephros and mesonephros), spleen, nares, and forebrain were the most commonly
      and severely affected tissues. In outbreaks, mortality was acute and numerous
      fish died over a 1-2 week period. Mortality continued until the majority of the
      population was lost, at which time the remaining fish were euthanized. In
      addition to these cases, four cultures of bacteria isolated from Zebrafish by
      another diagnostic laboratory were submitted to the Louisiana Aquatic Diagnostic
      Laboratory for identification and were confirmed as E. ictaluri. In total, eight
      cultures of E. ictaluri from Zebrafish from Louisiana, Massachusetts,
      Pennsylvania, and Florida were identified. The isolates were confirmed as E.
      ictaluri by biochemical phenotype, API 20E (bioMerieux), and amplification and
      sequencing of a portion of the 16S rRNA gene. Edwardsiella ictaluri isolates from
      Zebrafish are believed to comprise a unique group and were differentiated from
      catfish isolates by exhibiting weaker motility, autoaggregation in broth, a
      different plasmid profile (two plasmids of 4.0 and 3.5 kb), a different API 20E
      code (4204000), and lack of lipopolysaccharide recognition with Mab Ed9.

PMID- 23865819
TI  - Rapid cascade synthesis of poly-heterocyclic architectures from indigo.
AB  - The base-induced propargylation of the dye indigo results in the rapid and
      unprecedented one-pot synthesis of highly functionalized representatives of the
      pyrazino[1,2-a:4,3-a']diindole, pyrido[1,2-a:3,4-b']diindole and
      benzo[b]indolo[1,2-h]naphthyridine heterocyclic systems, with the last two
      reflecting the core skeleton of the anticancer/antiplasmodial marine natural
      products fascaplysin and homofascaplysins and a ring B-homologue, respectively.
      The polycyclic compounds 6-8, whose structures were confirmed through single
      crystal X-ray crystallographic analysis, arise from sequential
      inter/intramolecular substitution-addition reactions, and in some cases, ring
      rearrangement reactions. Preliminary studies on controlling the reaction path
      selectivity, and the potential reaction mechanisms, are also described. Initial
      biological activity studies with these new heterocyclic derivatives indicated
      promising in vitro antiplasmodial activity as well as good anticancer activity.
      The chemistry described is new for the indigo moiety and cascade reactions from
      this readily available and cheap starting material should be more broadly
      applicable in the synthesis of additional new heterocyclic systems difficult to
      access by other means. 

PMID- 23865818
TI  - Exposure to antiepileptic drugs in utero and child development: a prospective
      population-based study.
AB  - PURPOSE: Antiepileptic drugs may cause congenital malformations. Less is known
      about the effect on development in infancy and childhood. The aim of this study
      was to examine whether exposure to antiepileptic drugs during pregnancy has an
      effect on early child development. METHODS: From mid-1999 through December 2008,
      children of mothers recruited at 13-17 weeks of pregnancy were studied in the
      ongoing prospective Norwegian Mother and Child Cohort Study. Information on birth
      outcomes were obtained from the Medical Birth Registry (108,264 children), and
      mothers reported on their child's motor development, language, social skills, and
      autistic traits using items from standardized screening tools at 18 months
      (61,351 children) and 36 months (44,147 children) of age. The relative risk of
      adverse outcomes in children according to maternal or paternal epilepsy with and
      without prenatal exposure to antiepileptic drugs was estimated as odds ratios
      (ORs), using logistic regression with adjustment for maternal age, parity,
      education, smoking, depression/anxiety, folate supplementation, and child
      congenital malformation or low birth weight. KEY FINDINGS: A total of 333
      children were exposed to antiepileptic drugs in utero. At 18 months, the exposed
      children had increased risk of abnormal scores for gross motor skills (7.1% vs.
      2.9%; OR 2.0, 95% confidence interval [CI] 1.1-3.7) and autistic traits (3.5% vs.
      0.9%; OR 2.7, CI 1.1-6.7) compared to children of parents without epilepsy. At 36
      months, the exposed children had increased risk of abnormal score for gross motor
      skills (7.5% vs. 3.3%; OR 2.2, CI 1.1-4.2), sentence skills (11.2% vs. 4.8%; OR
      2.1, CI 1.2-3.6), and autistic traits (6.0% vs. 1.5%; OR 3.4, CI 1.6-7.0). The
      drug-exposed children also had increased risk of congenital malformations (6.1%
      vs. 2.9%; OR 2.1, CI 1.4-3.4), but exclusion of congenital malformations did not
      affect the risk of adverse development. Children born to women with epilepsy who
      did not use antiepileptic drugs had no increased risks. Children of fathers with
      epilepsy generally scored within the normal range. SIGNIFICANCE: Exposure to
      antiepileptic drugs during pregnancy is associated with adverse development at 18
      and 36 months of age, measured as low scores within key developmental domains
      rated by mothers. Exposures to valproate, lamotrigine, carbamazepine, or multiple
      antiepileptic drugs were associated with adverse outcome within different
      developmental domains.

PMID- 23865820
TI  - Need for objective and reproducible criteria in histopathological assessment of
      total mesorectal excision specimens: lessons from a national improvement project.
AB  - AIM: Data on quality control of the pathologic evaluation of total mesorectal
      excision (TME) specimens are scarce. We aimed to assess differences between
      evaluation by local pathologists participating in PROject on CAncer of the REctum
      (PROCARE; a Belgian improvement project on rectal cancer) and by a review panel
      of experts. METHOD: Based on photographic material and histopathology slides, a
      Review Committee of gastrointestinal expert pathologists re-evaluated the
      mesorectal plane, the tumour differentiation grade, the (y)pT stage and the
      tumour regression grade in 444 patients previously routinely assessed by local
      pathologists. RESULTS: The surgical plane was reported in 89% of patients and the
      circumferential resection margin in 88% of patients by the local pathologist. The
      median number of lymph nodes harvested in patients undergoing neoadjuvant
      radiochemotherapy was 11 and 14 in the other patients. The Review Committee
      downgraded the surgical plane from (intra)mesorectal to intramuscular in 17% of
      patients, and upgraded it from intramuscular to (intra)mesorectal in 27%. Tumour
      differentiation grade, T stage and tumour regression grade differed between local
      pathologists and the Review Committee in 15%, 10% and 38%, respectively, of
      patients. T stage was upgraded, mainly from T2 to T3, in 8% of patients. Tumour
      regression was judged by the Review Committee to be less advanced in 15% of
      patients. CONCLUSION: Acknowledging some shortcomings, this study gives a
      realistic view of clinical practice. There are differences in interpretation with
      regard to both macroscopic and microscopic analysis of TME specimens. These
      findings indicate a need for more objective and reproducible criteria in
      histopathology. Being aware of this is a first step for improvement.

PMID- 23865821
TI  - Association of metabolic syndrome with kidney function and histology in living
      kidney donors.
AB  - The selection of living kidney donors is based on a formal evaluation of the
      state of health. However, this spectrum of health includes subtle metabolic
      derangements that can cluster as metabolic syndrome. We studied the association
      of metabolic syndrome with kidney function and histology in 410 donors from 2005
      to 2012, of whom 178 donors were systematically followed after donation since
      2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a
      BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors
      received counseling on lifestyle modification. Metabolic syndrome was present in
      50 (12.2%) donors. Donors with metabolic syndrome were more likely to have
      chronic histological changes on implant biopsies than donors with no metabolic
      syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired
      kidney function recovery following donation. At last follow-up, reversal of
      metabolic syndrome was observed in 57.1% of donors with predonation metabolic
      syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p <
      0.001). In conclusion, metabolic syndrome in donors is associated with chronic
      histological changes, and nephrectomy in these donors was associated with
      subsequent protracted recovery of kidney function. Importantly, weight loss led
      to improvement of most abnormalities that define metabolic syndrome.

PMID- 23865822
TI  - Effect of the phospholipid chain length and head group on beta-phase formation of
      poly(9,9-dioctylfluorene) enclosed in liposomes.
AB  - We have studied the effect of head group and alkyl chain length on beta-phase
      formation in poly(9,9-dioctylfluorene) (PFO) solubilized in phospholipid
      liposomes. Systems studied have three different alkyl chain lengths (1,2
      dimyristoyl-sn-glycero-3-phosphatidylcholine [DMPC], 1,2-didodecanoyl-sn-glycero
      3-phosphatidylcholine [DLPC], 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine
      [DPPC]) and head groups (1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt
      [DMPA], 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine [DMPE] and 1,2
      dimyristoyl-sn-glycero-3-phospho-l-serine sodium salt [DMPS]). Changes in
      liposome size upon addition of PFO are followed by dynamic light scattering. All
      the phospholipids induce the formation of PFO beta-phase, which is followed by
      the emission intensity and deconvolution of the absorption spectra. Both the head
      group and alkyl chain length affect the yield of beta-phase. The photophysics of
      PFO incorporated in liposomes is characterized by stationary and time-resolved
      fluorescence, whereas the polymer-phospholipid interactions have been studied by
      the effect of the PFO concentration on the phospholipid phase transitions
      (differential scanning calorimetry [DSC]). 

PMID- 23865823
TI  - Improved post-partum follow-up of patients with gestational diabetes mellitus
      using HbA1c.

PMID- 23865824
TI  - Care providers' experiences of guidelines in daily work at a municipal
      residential care facility for older people.
AB  - AIM: To describe care providers' narrated experiences of guidelines in daily work
      at a municipal residential care facility for older people. BACKGROUND: Guidelines
      are used as a way of promoting high-quality health care. Most research concerning
      guidelines has focused on physician behaviour and to improve one specific aspect
      of care. Care providers working within municipal residential care of older people
      have described that working with multiple guidelines sometimes exposed them to
      contradictory demands and trouble their conscience. DESIGN: A qualitative
      descriptive design was adopted. METHODS: Interviews with eight care providers
      were carried out between February and March 2012 and analysed by qualitative
      content analysis. RESULTS: Care providers described experiences that guidelines
      are coming from above and are controlling and not sufficiently anchored at their
      workplace. Furthermore, they described guidelines as stealing time from
      residents, colliding with each other, lacking practical use and complicating
      care, and challenging care providers' judgment. The overall understanding is that
      care providers describe experiences of struggling to do their best, prioritising
      between arcane guidelines while keeping the residents' needs in the foreground.
      CONCLUSION: In order to prevent fragmented use, guidelines have to be coordinated
      and adapted to the reality of daily practice before implementation. It seems
      essential to provide opportunities for discussions between care providers,
      registered nurses and management about how to make guidelines work within their
      daily practice. Sufficient support, knowledge and involvement are likely key
      issues that can help care providers to constructively work according to
      guidelines and thus, by extension, improve the quality of care.

PMID- 23865825
TI  - Three-dimensional evaluation of upper airway following rapid maxillary expansion:
      a CBCT study.
AB  - OBJECTIVES: To evaluate, by using cone beam computed tomography, the skeletal,
      dental, oropharyngeal (OP) airway volume, and nasal passage (NP) volume changes
      that occur after rapid maxillary expansion (RME). MATERIALS AND METHODS: Two
      groups were selected, each with 35 patients (15 males, 20 females), an RME group
      (mean age, 14.02 +/- 1.46 years) and a control group (mean age, 14.10 +/- 1.44
      years). The RME group consisted of patients with maxillary constriction who were
      treated with Hyrax palatal expanders, and the control group comprised age- and
      sex-matched patients who underwent comprehensive orthodontic treatment without
      the use of a rapid maxillary expander. RESULTS: All of the transverse skeletal
      (medial orbital width, lateral nasal width, maxillary width, and mandibular
      width) and interdental (intermolar, interpremolar, and intercanine) parameters
      were significantly enlarged in the RME group. A statistically significant
      increase in airway variables was seen in both groups between pretreatment (T0)
      and final records (T1). The mean increase of NP airway volume for the RME group
      (1719.9 +/- 1510.7 mm(3)) was twofold compared with the control group (813.6 +/-
      1006.7 mm(3)), and no intergroup significant difference was found for the OP
      volume. CONCLUSIONS: Rapid maxillary expansion creates a significant increase in
      nasal passage airway volume but no significant change in the oropharyngeal airway
      volume.

PMID- 23865827
TI  - Acute and chronic effects of desvenlafaxine on gastrointestinal transit and
      motility in dogs.
AB  - BACKGROUND: Antidepressants are commonly used for treating functional
      gastrointestinal (GI) diseases. However, little is known whether antidepressants
      improve or impair GI motility. This study aimed at exploring possible effects of
      a serotonin-norepinephrine reuptake inhibitor, desvenlafaxine succinate (DVS), on
      GI motility in dogs. METHODS: Eight dogs chronically implanted with a duodenal
      cannula and a colon cannula were used in the study. Experiments were performed to
      assess the effects of a single dose of DVS (50 or 100 mg) and DVS given 50 mg
      once a day for 2 weeks on gastric emptying of solid, small intestinal transit,
      and colon transit and contractions. KEY RESULTS: (1) DVS significantly delayed
      gastric emptying of solid at a single dose of 50 or 100 mg. The inhibitory effect
      on gastric emptying was completely blocked by guanethidine (an adrenergic
      blocking agent). (2) DVS at a single dose of 50 or 100 mg accelerated colon
      transit, but showed no effects on small bowel transit. (3) DVS at a single dose
      of 50 mg enhanced colon contractions and guanethidine blocked the effect. (4)
      Surprisingly, DVS given at 50 mg once daily for 2 weeks did not alter gastric
      emptying, small bowel transit or colon transit. CONCLUSIONS & INFERENCES: Acute
      DVS delays gastric emptying of solid and enhances the contractions of the colon,
      which may be mediated via the sympathetic mechanism. Acute DVS promotes the
      transit of the colon but not the small intestine. However, chronic administration
      of DVS does not seem to alter GI motility.

PMID- 23865826
TI  - Comparison of T2 and T2*-weighted MR molecular imaging of a mouse model of
      glioma.
AB  - BACKGROUND: Standard MRI has been used for high-grade gliomas detection, albeit
      with limited success as it does not provide sufficient specificity and
      sensitivity to detect complex tumor structure. Therefore targeted contrast agents
      based on iron oxide, that shorten mostly T2 relaxation time, have been recently
      applied. However pulse sequences for molecular imaging in animal models of
      gliomas have not been yet fully studied. The aim of this study was therefore to
      compare contrast-to-noise ratio (CNR) and explain its origin using spin-echo
      (SE), gradient echo (GE), GE with flow compensation (GEFC) as well as
      susceptibility weighted imaging (SWI) in T2 and T2* contrast-enhanced molecular
      MRI of glioma. METHODS: A mouse model was used. U87MGdEGFRvIII cells (U87MG),
      derived from a human tumor, were injected intracerebrally. A 9.4 T MRI system was
      used and MR imaging was performed on the 10 day after the inoculation of the
      tumor. The CNR was measured prior, 20 min, 2 hrs and 24 hrs post intravenous tail
      administration of glioma targeted paramagnetic nanoparticles (NPs) using SE, SWI,
      GE and GEFC pulse sequences. RESULTS: The results showed significant differences
      in CNR among all pulse sequences prior injection. GEFC provided higher CNR post
      contrast agent injection when compared to GE and SE. Post injection CNR was the
      highest with SWI and significantly different from any other pulse sequence.
      CONCLUSIONS: Molecular MR imaging using targeted contrast agents can enhance the
      detection of glioma cells at 9.4 T if the optimal pulse sequence is used. Hence,
      the use of flow compensated pulse sequences, beside SWI, should to be considered
      in the molecular imaging studies.

PMID- 23865828
TI  - Application of RIFLE criteria in patients with multiple myeloma with acute kidney
      injury: a 15-year retrospective, single center, cohort study.
AB  - Abstract Although there have been numerous studies of patients with multiple
      myeloma (MM) and acute kidney injury (AKI), the results from these studies have
      varied greatly because of inconsistent definitions of AKI. The RIFLE criteria,
      which were designed to standardize the staging of AKI, have been extensively
      validated worldwide, but rarely in patients with MM. We retrospectively analyzed
      the natural history of 78 patients with MM and AKI between July 1995 and December
      2010. RIFLE criteria, solely on the basis of the serum creatinine standard, were
      applied to stage the severity of AKI as risk, injury or failure. Among patients
      at the risk, injury and failure stage, the chemotherapy response rates were
      54.5%, 63.6% and 39.3% (p = 0.26), and the renal response rates were 72.7%, 90.9%
      and 30.4%, respectively (p < 0.001). Severity of AKI predicted renal response but
      not chemotherapy response. Older age (odds ratio [OR] = 1.04, p = 0.01),
      hypercalcemia (OR = 2.57, p = 0.01) and reversibility of renal insufficiency (OR
      = 3.35 for no vs. yes, p < 0.001) were independent prognostic factors associated
      with survival. Severity of AKI staged by RIFLE class (OR = 2.04, failure stage
      vs. risk and injury stages. p = 0.06) was associated with marginally better long
      term outcome. The RIFLE criteria may play a critical role in the early prevention
      and management of AKI in this population. 

PMID- 23865829
TI  - The role of clonal evolution in smoldering multiple myeloma.

PMID- 23865830
TI  - Is it perhaps time for a comprehensive international prognostic index in chronic
      lymphocytic leukemia?

PMID- 23865831
TI  - Baseline low immunoglobulin A predicts inferior disease-free survival in
      pediatric acute myeloid leukemia and serial evaluation suggests role of
      immunoglobulin A in leukemogenesis.
AB  - Abstract Data on serial evaluation of immunoglobulins (Ig) in pediatric AML is
      lacking. From April 2010 to May 2011, 45 consecutive patients with AML aged 1-18
      years were prospectively enrolled along with nine healthy controls. Ig were
      assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow
      up and relapse. At diagnosis, Ig levels were significantly higher in patients
      than in healthy controls. Patienths with gum hypertrophy had low Ig levels (IgG,
      p = 0.007; IgA, p = 0.003; IgM, p = 0.06). Baseline Ig did not correlate with
      complete remission (CR). Patients who relapsed had a lower baseline IgA level
      than those in continuous CR (169 +/- 94 g/dL vs. 310 +/- 177 g/dL, p = 0.019).
      Patients with a low baseline IgA level (less than median) had inferior disease
      free-survival (DFS) on multivariate analysis (p = 0.048). Post-induction, IgM (p
      < 0.001) and IgA (p = 0.048) were significantly reduced as compared to their
      baseline values. On serial follow-up in patients who were in continuous CR, there
      was a significant decrease in IgA from post-induction until 6 months after
      treatment completion. This is the first study to evaluate the trend of humoral
      immunity in sequential pediatric patients with AML. Our study demonstrates that
      in pediatric AML, baseline Ig were higher than in controls. Gum hypertrophy was
      observed in patients with low Ig (IgA and IgG) levels. Relatively lower baseline
      IgA predicted disease relapse and inferior DFS. On serial follow-up, IgA
      significantly decreased in those who continued to stay in CR but not in patients
      who relapsed, suggesting an association of IgA with leukemogenesis. 

PMID- 23865832
TI  - Prevalence and patterns of cytomegalovirus DNAemia in adult patients with acute
      lymphoblastic leukemia on chemotherapy.

PMID- 23865833
TI  - Myeloma skews regulatory T and pro-inflammatory T helper 17 cell balance in favor
      of a suppressive state.
AB  - Abstract Discrepancies in the literature between regulatory T cell (Treg) and pro
      inflammatory T helper 17 (Th17) numbers in multiple myeloma (MM) can be largely
      explained by technical differences in methodology and patient selection. In this
      study, Treg cells were defined as CD3(+)CD4(+)CD25(++)CD127(lo) cells. Patients
      with MM (n = 20) had a significant imbalance in Treg/Th17 ratio when compared
      with either aged-matched controls (n = 28) or other monoclonal gammopathies, and
      this was associated with a significantly worse survival. The percent Treg in bone
      marrow of patients with MM was higher than that in matched peripheral blood
      samples (p = 0.02), although FOXP3 expression within bone marrow T cells was
      lower (p = 0.02). We observed increased Treg function, both in vivo and in vitro,
      due at least partially to an increase in CTLA-4 expression by concurrent
      treatment with dexamethasone and immune modulatory compounds (iMiDs). We suggest
      that immunoregulatory balance is important during active chemotherapy and that
      conclusions related to the immunostimulatory effect of iMiDs based on in vitro
      testing must be considered with caution. 

PMID- 23865834
TI  - Methylenetetrahydrofolate reductase gene haplotypes affect toxicity during
      maintenance therapy for childhood acute lymphoblastic leukemia in Japanese
      patients.
AB  - Abstract The aim of this study was to investigate the influence of daily 6
      mercaptopurine (6-MP) and low-dose weekly methotrexate (MTX) combination
      treatment and methylenetetrahydrofolate reductase (MTHFR) haplotypes on toxicity
      during maintenance therapy in Japanese childhood acute lymphoblastic leukemia
      (ALL). We retrospectively analyzed the MTHFR C677T and A1298C polymorphisms and
      influence of haplotypes on toxicity in 73 patients. Patients with the MTHFR 677TT
      and 677CT + 1298AC were associated with severe liver toxicity (p = 0.014, odds
      ratio [OR] = 3.82, 95% confidence interval [CI] = 1.27-11.46) and more rapid
      onset of liver toxicity (p = 0.010). Patients with MTHFR 677TT and 677CT + 1298AC
      were associated with lower frequency of 6-MP and MTX dose reduction due to
      leukopenia (p < 0.05). No difference was observed in average drug doses in the
      MTHFR genotypes. In conclusion, the MTHFR C677T and A1298C haplotypes might be
      useful for monitoring adverse effects in childhood ALL maintenance therapy in
      Japanese patients. 

PMID- 23865835
TI  - Management of relapsed/refractory mantle cell lymphoma: a review of current
      therapeutic strategies.
AB  - Abstract Despite recent advances in therapeutic strategies, a large proportion of
      patients with mantle cell lymphoma (MCL) experience progression after first-line
      treatment. Several attempts have been made to assess the role of different
      therapies for the treatment of patients with relapsed/refractory mantle cell
      lymphoma; however, a consensus on the optimal therapeutic strategy for each
      individual patient has not been reached. Overall, clinical evidence from phase II
      studies shows that high-dose cytarabine containing regimens, stem cell transplant
      and different biological agents all have promising activity with acceptable
      safety profiles. Therefore, these therapies can represent suitable treatment
      options for patients with relapsed/refractory MCL. Among different biological
      agents, at present only temsirolimus has been tested in a phase III study. This
      review considers available evidence on the management of relapsed/refractory MCL
      as discussed during a consensus meeting on the current treatment strategies for
      MCL. 

PMID- 23865836
TI  - Granular cell tumor of the breast detected on MRI screening.

PMID- 23865837
TI  - Antidiabetic activity of Kalanchoe pinnata in streptozotocin-induced diabetic
      rats by glucose independent insulin secretagogue action.
AB  - CONTEXT: Kalanchoe pinnata Lam. (Crassulaceae) is used as a traditional medicine
      worldwide to treat several ailments, including diabetes. However, the mechanism
      for the antihyperglycemic action is unknown. OBJECTIVE: The present study
      evaluates the antihyperglycemic and insulin secretagogue potential of Kalanchoe
      pinnata and assessment of the probable mechanism of action. MATERIALS AND
      METHODS: Steam distillate of Kalanchoe pinnata leaves was subjected to solvent
      fractionation and antidiabetic activity was detected in dichloromethane (DCM)
      fraction. In the in vivo studies, rats were treated with 5 and 10 mg/kg body
      weight of DCM fraction for 45 days orally. Lipid profile and other biochemical
      parameters were estimated. The probable mechanism for insulin secretagogue action
      was evaluated through studies using diazoxide and nifedipine. The bioactive
      component from DCM fraction was studied using HPTLC, GCMS and IR. RESULTS AND
      DISCUSSION: Fasting blood glucose values were reduced to 116 mg/dl from 228 mg/dl
      on treatment with 10 mg/kg body weight of DCM fraction, while glycated hemoglobin
      improved to 8.4% compared with 12.9% in diabetic controls. The insulin level and
      lipid profile values were close to normal values. In vitro studies demonstrated a
      dose-dependent insulin secretagogue action. Insulin secretion was 3.29-fold
      higher at 10 ug/ml as compared to the positive control. The insulin secretagogue
      activity was glucose independent and K(+)-ATP channel dependent. The bioactive
      component of the DCM fraction was identified to be a phenyl alkyl ether
      derivative. CONCLUSION: The DCM fraction of Kalanchoe pinnata demonstrates
      excellent insulin secretagogue action and can be useful in treatment of diabetes
      mellitus.

PMID- 23865838
TI  - A fast weak motif-finding algorithm based on community detection in graphs.
AB  - BACKGROUND: Identification of transcription factor binding sites (also called
      'motif discovery') in DNA sequences is a basic step in understanding genetic
      regulation. Although many successful programs have been developed, the problem is
      far from being solved on account of diversity in gene expression/regulation and
      the low specificity of binding sites. State-of-the-art algorithms have their own
      constraints (e.g., high time or space complexity for finding long motifs, low
      precision in identification of weak motifs, or the OOPS constraint: one
      occurrence of the motif instance per sequence) which limit their scope of
      application. RESULTS: In this paper, we present a novel and fast algorithm we
      call TFBSGroup. It is based on community detection from a graph and is used to
      discover long and weak (l,d) motifs under the ZOMOPS constraint (zero, one or
      multiple occurrence(s) of the motif instance(s) per sequence), where l is the
      length of a motif and d is the maximum number of mutations between a motif
      instance and the motif itself. Firstly, TFBSGroup transforms the (l, d) motif
      search in sequences to focus on the discovery of dense subgraphs within a graph.
      It identifies these subgraphs using a fast community detection method for
      obtaining coarse-grained candidate motifs. Next, it greedily refines these
      candidate motifs towards the true motif within their own communities. Empirical
      studies on synthetic (l, d) samples have shown that TFBSGroup is very efficient
      (e.g., it can find true (18, 6), (24, 8) motifs within 30 seconds). More
      importantly, the algorithm has succeeded in rapidly identifying motifs in a large
      data set of prokaryotic promoters generated from the Escherichia coli database
      RegulonDB. The algorithm has also accurately identified motifs in ChIP-seq data
      sets for 12 mouse transcription factors involved in ES cell pluripotency and self
      renewal. CONCLUSIONS: Our novel heuristic algorithm, TFBSGroup, is able to
      quickly identify nearly exact matches for long and weak (l, d) motifs in DNA
      sequences under the ZOMOPS constraint. It is also capable of finding motifs in
      real applications. The source code for TFBSGroup can be obtained from
      http://bioinformatics.bioengr.uic.edu/TFBSGroup/.

PMID- 23865839
TI  - Does metformin improve vascular health in children with type 1 diabetes? Protocol
      for a one year, double blind, randomised, placebo controlled trial.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of mortality in Type 1
      diabetes (T1D). Vascular dysfunction is an early and critical event in the
      development of cardiovascular disease. Children with T1D have vascular
      dysfunction therefore early interventions to improve vascular health are
      essential to reduce cardiovascular mortality in T1D. Metformin is an insulin
      sensitising agent which is known to improve vascular health outcomes in type 2
      diabetes (T2D) and other individuals with insulin resistance. It has been used
      safely in children and adolescents with T2D for over 10 years. This study aims to
      assess the effect of metformin on vascular health in children with T1D.
      METHODS/DESIGN: This study is a 12 month, double blind, randomised, placebo
      controlled trial to determine the effect of metformin on vascular health in
      children (age 8-18) with T1D. The sample size is 76 with 38 children in the
      metformin group and 38 children in the placebo group. Vascular health and
      biochemical markers will be measured at baseline, 3, 6 and 12 months. Vascular
      function will be measured using flow mediated dilatation and glyceryl trinitrate
      mediated dilatation of the brachial artery and vascular structure will be
      measured with carotid and aortic intima media thickness, using standardised
      protocols. DISCUSSION: This study will be the first to investigate the effect of
      metformin on vascular health in children with T1D. It will provide important
      information on a potential intervention to improve cardiovascular morbidity and
      mortality in this population at high risk from cardiovascular disease. TRIAL
      REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000148976.

PMID- 23865840
TI  - Continuous glucose monitoring pilot in low-income type 1 diabetes patients.
AB  - BACKGROUND: Continuous glucose monitoring (CGM) has been shown to be a valuable
      tool to improve glycemic control in patients with diabetes. The objective of this
      pilot study was to develop and implement CGM in an existing diabetes clinic for
      low-income patients on multiple daily injections. SUBJECTS AND METHODS: This was
      a single-center, prospective, randomized controlled, crossover pilot study.
      Initial focus groups were held to create low-literacy, Spanish and English guides
      to the use of carbohydrate counting and CGM. These tools were implemented to
      train participants on carbohydrate counting and insulin adjustments participants.
      Subjects were then randomized to start in Group A (CGM) or Group B (self
      monitoring blood glucose and then switched after 28 weeks). Hemoglobin A1c
      (HbA1c) was obtained at baseline and at the end of both study phases. RESULTS:
      Twenty-five economically challenged, primarily Latino participants with minimal
      prior education on intensive diabetes management completed the study. No
      significant reduction in HbA1c or decrease in time spent in parameters of low and
      high blood glucose was shown. However, eighty percent of participants who
      completed the study wanted to continue to use CGM once the research study was
      over. The participants also felt that the CGM made adjusting insulin easier.
      CONCLUSIONS: CGM can be implemented in patients from a low-income public clinic;
      however, HbA1c reduction was not achieved. Given the underlying lack of baseline
      self-management knowledge, a longer trial might be necessary to see benefit with
      CGM in this population.

PMID- 23865841
TI  - In silico design of optimal ratio for co-administration of pramlintide and
      insulin in type 1 diabetes.
AB  - BACKGROUND: The ability to simulate in silico experiments is crucial for fast and
      cost-effective preliminary studies prior to clinical trials. We present an in
      silico approach to the design of optimal pramlintide-to-insulin (P/I) ratios,
      using our computer simulator of the human metabolic system, with a population of
      virtual adult type 1 diabetes mellitus patients and with individual parameters
      modified to account for the dynamic effects of pramlintide. MATERIALS AND
      METHODS: A model of pramlintide action on gastric emptying was built using data
      of 15 type 1 diabetes mellitus subjects studied twice with a standardized dual
      tracer meal on placebo and pramlintide, which was incorporated in our type 1
      diabetes simulator. Extensive in silico experiments on 100 virtual subjects were
      performed to optimize the co-administration of pramlintide and insulin prior to
      its submission to clinical trials; several P/I ratios were tested in terms of
      efficacy, in attenuating postprandial hyperglycemia, and in hypoglycemia safety.
      RESULTS: In silico experiments estimated the optimal P/I ratio to be 9 MUg of
      pramlintide per unit (U) of insulin. Additional simulations narrowing the
      investigated range indicated that P/I ratios of 8 and 10 MUg/U would achieve
      similar performance. Moreover, simulation results suggested that in clinical
      trials, insulin boluses should be reduced by approximately 21% at a P/I ratio of
      9 MUg/U to account for the effects of pramlintide and avoid postprandial
      hypoglycemia. CONCLUSIONS: We can assert that a valid simulation model of
      pramlintide action was developed, leading to in silico estimation of optimal
      pramlintide:insulin co-administration ratio. Clinical trials will confirm (or
      adjust) this initial estimation.

PMID- 23865842
TI  - Synthesis of uniform disk-shaped copper telluride nanocrystals and cation
      exchange to cadmium telluride quantum disks with stable red emission.
AB  - We present the synthesis of novel disk-shaped hexagonal Cu2Te nanocrystals with a
      well-defined stoichiometric composition and tunable diameter and thickness.
      Subsequent cation exchange of Cu to Cd at high temperature (180  degrees C)
      results in highly fluorescent CdTe nanocrystals, with less than 1 mol % of
      residual Cu remaining in the lattice. The procedure preserves the overall disk
      shape, but is accompanied by a substantial reconstruction of the anion
      sublattice, resulting in a reorientation of the c-axis from the surface normal in
      Cu2Te into the disk plane in CdTe nanodisks. The synthesized CdTe nanodisks show
      a continuously tunable photoluminescence (PL) peak position, scaling with the
      thickness of the disks. The PL lifetime further confirms that the CdTe PL arises
      from band-edge exciton recombination; that is, no Cu-related emission is
      observed. On average, the recombination rate is about 25-45% faster with respect
      to their spherical quantum dots counterparts, opening up the possibility to
      enhance the emission rate at a given wavelength by controlling the nanocrystal
      shape. Finally, with a PL quantum efficiency of up to 36% and an enhanced PL
      stability under ambient conditions due to a monolayer of CdS formed on the
      nanocrystal surface during cation exchange, these flat quantum disks form an
      interesting enrichment to the current family of highly fluorescent, shape
      controlled nanocrystals. 

PMID- 23865843
TI  - Pancreaticoduodenectomy in elderly adults: is it justified in terms of mortality,
      long-term morbidity, and quality of life?
AB  - OBJECTIVES: To evaluate long-term morbidity, mortality, and quality of life (QoL)
      after pancreaticoduodenectomy (PD) in elderly adults. DESIGN: Retrospective
      cohort study. SETTING: Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
      PARTICIPANTS: One hundred and sixty-eight individuals aged 70 and older who
      underwent PD between 1995 and 2010. MEASUREMENTS: A prospective pancreatic
      surgery database was analyzed for postoperative morbidity; mortality; intensive
      care unit (ICU), hospital, and rehabilitation facility stay; and readmissions
      after surgery. QoL was assessed using a validated questionnaire completed 3, 6,
      and 12 months after surgery. RESULTS: Seventy-two percent of the participants had
      an American Society of Anesthesiologists score of 3 or greater. There was no
      intraoperative death. Thirty- and 60-day postoperative mortality rates were 5.9%
      and 6.5%, respectively. Median ICU stay was 2 days, and median hospital stay was
      22 days. Sixty-four participants (37.5%) were discharged to a rehabilitation
      facility. The first-year readmission rate was 31%. One- and 2-year overall
      survival rates were 58% and 36%, respectively. Global QoL scores 3 and 12 months
      after surgery were 68% and 73%, respectively. Scores were lower yet comparable
      with those of matched individuals undergoing laparoscopic cholecystectomy.
      CONCLUSION: Most elderly adults with pancreatic cancer survive longer than 1 year
      after PD; 36% survive longer than 2 years. These individuals are likely to have
      acceptable long-term morbidity and overall good QoL, corresponding with their
      age.

PMID- 23865844
TI  - Redox-sensitive DNA binding by homodimeric Methanosarcina acetivorans MsvR is
      modulated by cysteine residues.
AB  - BACKGROUND: Methanoarchaea are among the strictest known anaerobes, yet they can
      survive exposure to oxygen. The mechanisms by which they sense and respond to
      oxidizing conditions are unknown. MsvR is a transcription regulatory protein
      unique to the methanoarchaea. Initially identified and characterized in the
      methanogen Methanothermobacter thermautotrophicus (Mth), MthMsvR displays
      differential DNA binding under either oxidizing or reducing conditions. Since
      MthMsvR regulates a potential oxidative stress operon in M. thermautotrophicus,
      it was hypothesized that the MsvR family of proteins were redox-sensitive
      transcription regulators. RESULTS: An MsvR homologue from the methanogen
      Methanosarcina acetivorans, MaMsvR, was overexpressed and purified. The two MsvR
      proteins bound the same DNA sequence motif found upstream of all known MsvR
      encoding genes, but unlike MthMsvR, MaMsvR did not bind the promoters of select
      genes involved in the oxidative stress response. Unlike MthMsvR that bound DNA
      under both non-reducing and reducing conditions, MaMsvR bound DNA only under
      reducing conditions. MaMsvR appeared as a dimer in gel filtration chromatography
      analysis and site-directed mutagenesis suggested that conserved cysteine residues
      within the V4R domain were involved in conformational rearrangements that impact
      DNA binding. CONCLUSIONS: Results presented herein suggest that homodimeric
      MaMsvR acts as a transcriptional repressor by binding Ma PmsvR under non-reducing
      conditions. Changing redox conditions promote conformational changes that
      abrogate binding to Ma PmsvR which likely leads to de-repression.

PMID- 23865845
TI  - Changing bodies, changing habits: women's experiences of interval training
      following gastric bypass surgery.
AB  - Patients undergoing weight-loss surgery are increasingly encouraged to change
      their lifestyles. Dietary interventions combined with physical exercise
      interventions are regarded as the most effective way to ensure that they do not
      regain the weight they have lost. Little research however, has been done on how
      patients who have had the surgery actually experience the process of changing
      their exercise habits. To help fill this gap, we investigated the experiences of
      women participating in a group-based rehabilitation program designed to radically
      transform these habits. Based on participant observation, and our interviews with
      11 women in the program, we were able to identify a variety of potential benefits
      and negative consequences in group training, organized according to the interval
      principle. We also found that the experiences of these women were closely related
      to their views on how significantly the surgery had changed their lifestyle.
      Based on the experiences related by these women, we believe that the
      "effectiveness" of standardized group-based interventions for patients undergoing
      weight-loss surgery should be reconsidered. Some of the women in our study viewed
      the group-based standardized training intervention positively; others resisted
      it. Our research leads us to conclude that this type of program could be more
      successful if the forms of activity and their intensity were customized to meet
      the needs and desires of each participant. 

PMID- 23865846
TI  - Expression and functional relevance of UGT1A4 in a cohort of human drug-resistant
      epileptic brains.
AB  - PURPOSE: Brain drug bioavailability is regulated by the blood-brain barrier
      (BBB). It was recently suggested that cytochrome P450 (CYP) enzymes could act in
      concert with multidrug transporter proteins to regulate drug penetration and
      distribution into the diseased brain. The possibility that phase II metabolic
      enzymes could be expressed in the epileptic brain has been not evaluated. Phase
      II enzymes are involved in the metabolism of common antiepileptic drugs (AEDs).
      METHODS: Phase II enzyme UGT1A4 brain expression was evaluated in temporal lobe
      resections from patients with epilepsy. UGT1A4 expression was determined by
      western blot and immunocytochemistry in primary cultures of human drug-resistant
      brain endothelial human brain epileptic endothelial cells (EPI-EC)s and
      commercially available control cells human brain microvascular endothelial cells
      (HBMECs). Lack of DNA condensation measured by 4',6-diamidino-2-phenylindole
      (DAPI) was used as a surrogate marker of cell viability and was correlated to
      UGT1A4 expression high performance liquid chromatography ultraviolet detection
      (HPLC-UV) was used to quantify lamotrigine metabolism by EPI-EC and HBMEC. The
      appearance of the specific lamotrigine metabolite, 2-n glucuronide (MET-1), was
      also evaluated. Lamotrigine and MET-1 levels were measured in selected surgical
      brain and matched blood samples. KEY FINDINGS: UGT1A4 expression was observed in
      BBB endothelial cells and neurons. Our quantification study revealed variable
      levels of UGT1A4 expression across the brain specimens analyzed. Neurons devoid
      of UGT1A4 expression displayed nuclear DAPI condensation, a sign of cellular
      distress. UGT1A4 overexpression in EPI-EC, as compared to HBMEC, was reflected by
      a proportional increase in lamotrigine metabolism. The lamotrigine metabolite,
      MET-1, was formed in vitro by EPI-EC and, to a lesser extent, by HBMEC. HPLC-UV
      measurements of brain and blood samples obtained from patients receiving
      lamotrigine prior to surgery revealed the presence of lamotrigine and its
      metabolites in the brain. SIGNIFICANCE: These initial results suggest the
      presence of a phase II enzyme in the epileptic brain. Further studies are
      required to fully describe the pattern of brain UGT1A4 expression in relation to
      clinical variables and drug resistance.

PMID- 23865847
TI  - Causes of sudden death in patients with obstructive sleep apnea.
AB  - There are few autopsy studies of patients dying suddenly with obstructive sleep
      apnea (OSA). Twenty-five forensic autopsies of unexpected sudden death in
      individuals with OSA were reviewed. The causes of death were as follows:
      cardiomyopathy (n = 11); sudden unexpected death without morphologic findings
      (SUDNA, n = 6); and other cardiovascular diseases not related to OSA (n = 8). The
      cardiomyopathy group comprised five hearts with concentric left ventricular
      hypertrophy without dilatation and six with left ventricular diameter >4 cm
      (dilated cardiomyopathy). Four of six hearts in the SUDNA group showed right
      ventricular dilatation compared with seven of 11 showed cardiomyopathy and one of
      eight miscellaneous. The degree of obesity was greatest in the dilated
      cardiomyopathy group (10 of 11 obese) followed by the SUDNA group (four of six
      obese). The cardiac findings in patients dying suddenly and unexpectedly with OSA
      include nonspecific cardiomyopathy, other cardiac conditions, and hearts without
      a morphologic cause of death, which show frequent right ventricular dilatation as
      the only finding. 

PMID- 23865848
TI  - Does the location of the ulcer affect the interpretation of the probe-to-bone
      test in the diagnosis of osteomyelitis in diabetic foot ulcers?

PMID- 23865849
TI  - A radical cascade cyclization to prepare dihydrothiophenes induced by thiyl
      radicals as sulfur biradical equivalents.
AB  - Bicyclic dihydrothiophenes are readily prepared by a radical cascade cyclization
      reaction triggered by the addition of a thiyl radical under thermal or
      photoirradiation conditions. The translocated radical attacks the sulfur atom in
      the initial radical donor unit in an SHi manner. Sufficient stereoselectivity is
      achieved when a large excess of disulfide is used for the reaction under
      photoirradiation conditions. The reaction in the absence of solvents provides
      vinylsulfides instead of dihydrothiophenes. Thus, the sulfur atom in the thiyl
      radical serves as a sulfur biradical synthetic equivalent. 

PMID- 23865850
TI  - Sensitive, site-specific, and stable vibrational probe of local protein
      environments: 4-azidomethyl-L-phenylalanine.
AB  - We have synthesized the unnatural amino acid (UAA), 4-azidomethyl-L-phenylalanine
      (pN3CH2Phe), to serve as an effective vibrational reporter of local protein
      environments. The position, extinction coefficient, and sensitivity to local
      environment of the azide asymmetric stretch vibration of pN3CH2Phe are compared
      to the vibrational reporters: 4-cyano-L-phenylalanine (pCNPhe) and 4-azido-L
      phenylalanine (pN3Phe). This UAA was genetically incorporated in a site-specific
      manner utilizing an engineered, orthogonal aminoacyl-tRNA synthetase in response
      to an amber codon with high efficiency and fidelity into two distinct sites in
      superfolder green fluorescent protein (sfGFP). This allowed for the dependence of
      the azide asymmetric stretch vibration of pN3CH2Phe to different protein
      environments to be measured. The photostability of pN3CH2Phe was also measured
      relative to the photoreactive UAA, pN3Phe.

PMID- 23865851
TI  - Chlorophyll J-aggregates: from bioinspired dye stacks to nanotubes, liquid
      crystals, and biosupramolecular electronics.
AB  - Among the natural light-harvesting (LH) systems, those of green sulfur and
      nonsulfur photosynthetic bacteria are exceptional because they lack the support
      of a protein matrix. Instead, these so-called chlorosomes are based solely on
      "pigments". These are self-assembled bacteriochlorophyll c, d, and e derivatives,
      which consist of a chlorophyll skeleton bearing a 3(1)-hydroxy functional group.
      Chemists consider the latter as an essential structural unit to direct the
      formation of light-harvesting self-assembled dye aggregates with J-type excitonic
      coupling. The intriguing properties of chlorosomal J-type aggregates,
      particularly narrow red-shifted absorption bands, compared with monomers and
      their ability to delocalize and migrate excitons, have inspired intense research
      activities toward synthetic analogues in this field. The ultimate goal of this
      research field is the development of (opto-)electronic devices based on the
      architectural principle of chlorosomal LH systems. In this regard, the challenge
      is to develop small, functional building blocks with appropriate substituents
      that are preprogrammed to self-assemble across different length scales and to
      emulate functions of natural LH systems or to realize entirely new functions
      beyond those found in nature. In this Account, we highlight our achievements in
      the past decade with semisynthetic zinc chlorins (ZnChls) as model compounds of
      bacteriochlorophylls obtained from the naturally most abundant chlorin precursor:
      chlorophyll a. To begin, we explore how supramolecular strategies involving pi
      stacking, hydrogen bonding, and metal-oxygen coordination can be used to design
      ZnChl-based molecular stack, tube, and liquid crystalline assemblies conducive to
      charge and energy transport. Our design principle is based on the bioinspired
      functionalization of the 3(1)-position of ZnChl with a hydroxy or methoxy group;
      the former gives rise to tubular assemblies, whereas the latter induces stack
      assemblies. Functionalization of the 17(2)-position with esterified hydrophilic
      or hydrophobic chains, dendron-wedge substituents, and chromophores having
      complementary optical properties such as naphthalene bisimides (NBIs) is used to
      modulate the self-assembly of ZnChl dyes. The resulting assemblies exhibit
      enhanced charge transport and energy transfer abilities. We have used UV/vis,
      circular dichroism (CD), fluorescence spectroscopy, and dynamic light scattering
      (DLS) for the characterization of these assemblies in solution. In addition, we
      have studied assembly morphologies by atomic force microscopy (AFM), scanning
      tunneling microscopy (STM), transmission electron microscopy (TEM), and cryogenic
      TEM. Crystallographic techniques such as powder X-ray and solid-state NMR have
      been used to explain the precise long- and short-range packing of dyes in these
      assemblies. Finally, functional properties such as charge and energy transport
      have been explored by pulse radiolysis time-resolved microwave conductivity (PR
      TRMC), conductive AFM, and time-resolved fluorescence spectroscopy. The design
      principles discussed in this Account are important steps toward the utilization
      of these materials in biosupramolecular electronics and photonics in the future. 

PMID- 23865854
TI  - Abstracts of the Prostate Cancer World Congress & 14th Australasian Prostate
      Cancer Conference. Melbourne, Australia. August 6-10, 2013.

PMID- 23865852
TI  - Kidney allograft survival after acute rejection, the value of follow-up biopsies.
AB  - Kidney allografts are frequently lost due to alloimmunity. Still, the impact of
      early acute rejection (AR) on long-term graft survival is debated. We examined
      this relationship focusing on graft histology post-AR and assessing specific
      causes of graft loss. Included are 797 recipients without anti-donor antibodies
      (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR
      diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic
      types of AR led to abnormal histology in 1 and 2 years protocol biopsies,
      including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis
      (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001).
      AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p <
      0.0001). However, only those AR episodes followed by abnormal histology led to
      reduced graft survival. Early AR related to more late alloimmune-mediated graft
      losses, particularly transplant glomerulopathy (31% of losses). Related to this
      outcome, recipients with AR were more likely to have new DSA class II 1 year
      posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients,
      early AR often leads to persistent graft inflammation and increases the risk of
      new DSA II production. Both of these post-AR events are associated with increased
      risk of graft loss.

PMID- 23865855
TI  - CELDA -- an ontology for the comprehensive representation of cells in complex
      systems.
AB  - BACKGROUND: The need for detailed description and modeling of cells drives the
      continuous generation of large and diverse datasets. Unfortunately, there exists
      no systematic and comprehensive way to organize these datasets and their
      information. CELDA (Cell: Expression, Localization, Development, Anatomy) is a
      novel ontology for the association of primary experimental data and derived
      knowledge to various types of cells of organisms. RESULTS: CELDA is a structure
      that can help to categorize cell types based on species, anatomical localization,
      subcellular structures, developmental stages and origin. It targets cells in
      vitro as well as in vivo. Instead of developing a novel ontology from scratch, we
      carefully designed CELDA in such a way that existing ontologies were integrated
      as much as possible, and only minimal extensions were performed to cover those
      classes and areas not present in any existing model. Currently, ten existing
      ontologies and models are linked to CELDA through the top-level ontology BioTop.
      Together with 15.439 newly created classes, CELDA contains more than 196.000
      classes and 233.670 relationship axioms. CELDA is primarily used as a
      representational framework for modeling, analyzing and comparing cells within and
      across species in CellFinder, a web based data repository on cells
      (http://cellfinder.org). CONCLUSIONS: CELDA can semantically link diverse types
      of information about cell types. It has been integrated within the research
      platform CellFinder, where it exemplarily relates cell types from liver and
      kidney during development on the one hand and anatomical locations in humans on
      the other, integrating information on all spatial and temporal stages. CELDA is
      available from the CellFinder website: http://cellfinder.org/about/ontology.

PMID- 23865856
TI  - 'Pathognomonic' muscle imaging findings in DNAJB6 mutated LGMD1D.
AB  - BACKGROUND AND PURPOSE: We have previously reported clinical, genetic and
      molecular pathomechanistic findings in DNAJB6 mutated LGMD1D. After publishing
      clinical findings of the original Finnish family we identified more Finnish,
      Italian and US families with the same disease, ultimately confirmed by mutations
      in the same gene. METHODS: Of the total number of 28 examined Finnish and Italian
      patients 23 underwent lower limb muscle imaging. RESULTS: At the early stages of
      the disease fatty degeneration in T1-weighed MRI sequences were observed in the
      soleus, adductor magnus, semimembranosus and biceps femoris muscles followed by
      medial gastrocnemius, adductor longus and later by vasti muscles of the
      quadriceps. Rectus femoris, lateral gastrocnemius, sartorius, gracilis and the
      anterolateral group of the lower leg muscles were spared until late senecence.
      The pattern of differential involvement could be identified at different stages
      of the disease process. CONCLUSIONS: Since the general clinical findings do not
      provide clues for diagnosis this distinct pattern of muscle involvement and
      pathognomonic imaging findings are highly relevant in the clinical setting. The
      pattern of muscle involvement is so typical that it can be used as a differential
      diagnostic tool for LGMD1D. The final diagnosis however requires molecular
      genetic confirmation.

PMID- 23865857
TI  - Musical taste, employment, education, and global region.
AB  - Sociologists have argued that musical taste should vary between social groups,
      but have not considered whether the effect extends beyond taste into uses of
      music and also emotional reactions to music. Moreover, previous research has
      ignored the culture in which participants are located. The present research
      employed a large sample from five post-industrial global regions and showed that
      musical taste differed between regions but not according to education and
      employment; and that there were three-way interactions between education,
      employment, and region in the uses to which participants put music and also their
      typical emotional reactions. In addition to providing partial support for
      existing sociological theory, the findings highlight the potential of culture as
      a variable in future quantitative research on taste. 

PMID- 23865858
TI  - Dioxygen-triggered oxidative radical reaction: direct aerobic difunctionalization
      of terminal alkynes toward beta-keto sulfones.
AB  - An unprecedented dioxygen-triggered oxidative radical process was explored using
      dioxygen as the solely terminal oxidant, realizing aerobic oxidaitve
      difunctionalization of terminal alkynes toward beta-keto sulfones with high
      selectivity. Operando IR experiments revealed that pyridine not only acts as a
      base to successfully surpress ATRA (atom transfer radical addition) process, but
      also plays a vital role in reducing the activity of sulfinic acids. 

PMID- 23865860
TI  - Comparison of the shear bond strength of orthodontic brackets in bonding and
      rebonding: preparation with laser versus conventional acid etch technique.
AB  - OBJECTIVE: The purpose of this study was to compare the bond strength of
      orthodontic brackets using laser versus acid etching. BACKGROUND DATA: Debonding
      of brackets is a common problem in orthodontic treatments. MATERIALS AND METHODS:
      Eighty extracted premolar teeth were divided into two groups. The enamel of the
      teeth in group A and B were etched using CO2 laser and phosphoric acid,
      respectively. The brackets were bonded to the teeth using Transbond XT and then
      debonded from the teeth by Instron machine. The remaining composite on the tooth
      surface was removed by a tungsten carbide polishing bur. Both groups were divided
      into two subgroups (A1, A2 and B1, B2). The teeth were prepared again with laser
      in A1, B1 subgroups and with acid in A2, B2 subgroups. At each stage, the shear
      bond strength and residual adhesive index were measured. One way ANOVA and chi(2)
      tests were used to analyze data. RESULTS: The mean shear bond strength was
      significantly lower in group A and higher in group B compared with all other
      groups (p < 0.05). Most of the bond failures were degree 0 and 1 in groups A, A1,
      and B1, and degree 2 and 3 in groups B, A2, and B2. CONCLUSIONS: Primary
      preparation with acid has a higher bond strength value than does CO2 laser. Less
      adhesive residue remained on enamel after tooth preparation with laser following
      debonding. Secondary preparation of the enamel using laser has higher bond
      strength value than does primary preparation with laser, which can rationalize
      use of laser in rebonding of brackets.

PMID- 23865859
TI  - Dental caries in older adults in the last year of life.
AB  - OBJECTIVES: To examine dental caries severity (measured by number of carious
      teeth) in older adults in the last year of life. DESIGN: Cross-sectional study
      based on dental records. SETTING: Community-based geriatric dental clinic.
      PARTICIPANTS: One thousand two hundred sixteen individuals aged 65 and older,
      including 168 individuals in the last year of life (e.g., individuals died within
      1 year after their new-patient examinations). MEASUREMENTS: Information on
      socioeconomic, medical history, medication, functional status, and oral health
      measures, including number of carious teeth, was abstracted from dental records.
      End-of-life status was determined using the National Death Index. Propensities of
      death were calculated using a logistic regression and then adjusted together with
      mobility and oral care function in the multivariable regression model to examine
      the effect of end-of-life status on dental caries. RESULTS: Caries severity
      differed in end-of-life participants with different oral care function. Of those
      needing help with oral care, end-of-life participants had only a slightly higher
      and nonstatistically significant risk (7.5 vs 6.1, adjusted incidence density
      ratio (IDR) = 1.12, 95% confidence interval (CI) = 0.85-1.48) of having more
      carious teeth than those not in the last year of life. On the other hand, caries
      severity was lower in end-of-life participants without impaired oral care
      function (IDR = 0.53, 95% CI = 0.30-0.92). CONCLUSION: Oral care function
      modifies the association between caries severity and end-of-life status.
      Individuals who could maintain oral hygiene independently had a low level of
      caries at the end of life, however, dental caries had increased before
      functionally dependent individuals entered their last year of life.

PMID- 23865861
TI  - Bilateral radiation-induced angiosarcoma of the breast.

PMID- 23865862
TI  - Efflux system overexpression and decreased OprD contribute to the carbapenem
      resistance among extended-spectrum beta-lactamase-producing Pseudomonas
      aeruginosa isolates from a Chinese university hospital.
AB  - The aim of this study was to investigate, for the first time, the combinations of
      carbapenem resistance mechanisms in clinical isolates of extended-spectrum beta
      lactamase (ESBL)-producing Pseudomonas aeruginosa in a Chinese hospital. Pulsed
      field gel electrophoresis revealed the presence of eight clonal types among the
      15 ESBL producers. Multilocus sequence typing of two isolates harboured blaIMP-1
      identified the clonal strain as ST325. All these genes were found either alone or
      simultaneously in the strains in the following five different
      arrangements:<blaOXA-10>; <blaOXA-10, blaIMP-1>; <blaPER-1, blaOXA-10>; <blaPER
      1, blaPSE-1>; <blaOXA-10, blaTEM-1>. Regarding mutation-driven resistance, all,
      but four of the isolates had a relevant decrease of oprD expression. In addition,
      73.3% of the isolates overexpressed mexB, 40% mexD, and 33.3% mexY. A specific
      combination of overexpressed mexB or mexY and alteration in loop L710 of OprD
      were significantly associated with meropenem resistance. In conclusion,
      combination of several mutation-driven mechanisms leading to OprD inactivation
      and overexpression of efflux systems was the main carbapenem resistance mechanism
      among the ESBL-producing P. aeruginosa isolates, but acquisition of a
      transferable resistance determinant such as metallo-beta-lactamase could be
      problematic in clinical settings in China. 

PMID- 23865863
TI  - Optimism and coping strategies among Caucasian, Korean, and African American
      older women.
AB  - Coping strategies and optimism have significant effects on the health of older
      women. Culture affects coping behaviors used to deal with stress. We examined the
      relationship between optimism and coping strategies used to manage daily stress
      and health among community-dwelling Caucasian, Korean American, and African
      American women. Data were collected from 373 women over the age of 65. Results
      showed that each group used different coping strategies. The more optimistic used
      more problem-focused and adaptive copings, while the less optimistic employed
      more avoidant copings. Differences in cultural background and individual levels
      of optimism guided their coping strategies. 

PMID- 23865864
TI  - Cytochrome P450 2J2: distribution, function, regulation, genetic polymorphisms
      and clinical significance.
AB  - Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic
      tissues, with predominant expression in the cardiovascular systems and lower
      levels in the intestine, kidney, lung, pancreas, brain, liver, etc. During the
      past 15 years, CYP2J2 has attracted much attention for its epoxygenase activity
      in arachidonic acid (AA) metabolism. It converts AA to four epoxyeicosatrienoic
      acids (EETs) that have various biological effects, especially in the
      cardiovascular systems. In recent publications, CYP2J2 is shown highly expressed
      in various human tumor cells, and its EET metabolites are demonstrated to
      implicate in the pathologic development of human cancers. CYP2J2 is also a human
      CYP that involved in phase I xenobiotics metabolism. Antihistamine drugs and many
      other compounds were identified as the substrates of CYP2J2, and studies have
      demonstrated that these substrates have a broad structural diversity. CYP2J2 is
      found not readily induced by known P450 inducers; however, its expression could
      be regulated in some pathological conditions, might through the activator protein
      1(AP-1), the AP-1-like element and microRNA let-7b. Several genetic mutations in
      the CYP2J2 gene have been identified in humans, and some of them have been shown
      to have potential associations with some diseases. With the increasing awareness
      of its roles in cancer disease and drug metabolism, studies about CYP2J2 are
      still going on, and various inhibitors of CYP2J2 have been determined. Further
      studies are needed to delineate the roles of CYP2J2 in disease pathology, drug
      development and clinical practice.

PMID- 23865865
TI  - Pharmacokinetic drug interactions involving Ginkgo biloba.
AB  - Ginkgo biloba leaf extracts (GLEs) are popular herbal remedies for the treatment
      of Alzheimer's dementia, tinnitus, vertigo and peripheral arterial disease. As
      GLEs are taken regularly by older people who are likely to also use multiple
      other drugs for the treatment of, e.g. hypertension, diabetes, rheumatism or
      heart failure, potential herb-drug interactions are of interest. Preclinical
      studies of high doses/concentrations of GLEs of varying quality and
      standardization hinted at both an inhibition and induction of metabolic enzymes
      and transporters. However, in humans, positive in vitro-findings could not be
      replicated in vivo. At maximum recommended doses of 240 mg/day, a clinically
      relevant interaction potential of the standardized GLE EGb 761 could not be
      shown. GLE doses higher than the recommended ones led to a weak induction of the
      CYP2C19-mediated omeprazole 5-hydroxylation, and a weak inhibition of the CYP3A4
      mediated midazolam 1'-hydroxylation, respectively. Also, the regular intake of a
      poorly characterized GLE at a dose of 360 mg/day slightly increased the
      bioavailability of talinolol, a substrate of P-glycoprotein and various organic
      anion-transporting polypeptides. Thus, regarding pharmacokinetic herb-drug
      interactions, the intake of the standardized GLE, EGb 761, together with
      synthetic drugs appears to be safe as long as daily doses up to 240 mg are
      consumed. If this applies to other extracts prepared according to the European
      Pharmacopoeia remains uncertain. Also, a relevant potential for drug interactions
      cannot be excluded for poorly standardized GLEs used in many food supplements.

PMID- 23865866
TI  - Lack of association between Fas rs180082 polymorphism and risk of cervical
      cancer: an update by meta-analysis.
AB  - BACKGROUND: The Fas rs180082 polymorphism has been reported to be associated with
      cervical cancer susceptibility, yet the results of these previous results have
      been inconsistent or controversial. The objective of this study was to explore
      whether the Fas rs180082 polymorphism confers susceptibility to cervical cancer.
      METHODS: The relevant studies were identified through a search of PubMed,
      Excerpta Medica Database (Embase), Elsevier Science Direct and Chinese Biomedical
      Literature Database (CBM) until July 2012. The association between the Fas
      rs180082 polymorphism and cervical cancer risk was assessed by odds ratios (ORs)
      together with their 95% confidence intervals (CIs). RESULTS: A total of 7 case
      control studies were eventually identified. We found no association between Fas
      rs180082 polymorphism and cervical cancer susceptibility in overall population (G
      versus A: OR = 1.03, 95% CI = 0.99-1.07, P = 0.197; AG + GG versus AA: OR = 1.04,
      95% CI = 0.98-1.09, P = 0.176; GG versus AA + AG: OR = 1.04, 95% CI = 0.84-1.31,
      P = 0.701). In subgroup analysis, similar results were found in Asian (G versus
      A: OR = 1.06, 95% CI = 0.97-1.15, P = 0.195; AG + GG versus AA: OR = 1.08, 95% CI
      = 0.98-1.19, P = 0.176; GG versus AA + AG: OR = 0.97, 95% CI = 0.51-1.84, P =
      0.935) and African (G versus A: OR = 1.01, 95% CI = 0.97-1.15, P = 0.195; AG + GG
      versus AA: OR = 0.99, 95% CI = 0.91-1.07, P = 0.739; GG versus AA + AG: OR =
      1.09, 95% CI = 0.94-1.25, P = 0.745). CONCLUSION: This meta-analysis has shown
      that there is a lack of association of the Fas rs180082 polymorphisms with
      cervical cancer susceptibility. However, larger scale primary studies with the
      consideration of gene-gene and gene-environment interactions are still required
      to further evaluate the interaction of Fas rs180082 polymorphism with cervical
      cancer susceptibility.

PMID- 23865867
TI  - Variant MBL2 genotypes producing low mannose-binding lectin may increase risk of
      Bacillus Calmette-Guerin osteitis in vaccinated newborns.
AB  - AIM: The aim of this study was to evaluate whether mannose-binding lectin (MBL)
      plays a role in the development of osteitis after Bacillus Calmette-Guerin (BCG)
      vaccination as a newborn. METHODS: Blood samples were obtained from 132 former
      BCG osteitis patients, now aged 21-49 years, and analysed for MBL concentration
      and MBL2 genotype in a controlled setting. RESULTS: Variant genotypes in the MBL2
      gene were more common in the former BCG osteitis patients (42.4%) than in the
      population controls (32.3%, p = 0.033). However, MBL concentrations at the age of
      21-49 years were not lower in these patients than in the controls in the same age
      group. The variant MBL2 genotypes were associated with low serum MBL
      concentrations, and moreover, MBL concentration was not measurable in two of
      those three patients who were homozygous for the variant MBL2 genotype. Low serum
      MBL concentrations were not associated with any illnesses in the medical history
      of the BCG patients, their siblings or children. CONCLUSION: Preliminary evidence
      was found that variant, low-MBL-producing genotypes may be associated with the
      increased risk of BCG osteitis in vaccinated newborns.

PMID- 23865869
TI  - Confronting the problem of overweight pets.

PMID- 23865870
TI  - Competition in drug sales.

PMID- 23865871
TI  - Cultural competence in veterinary practice.

PMID- 23865872
TI  - What is your diagnosis? Osteosarcoma.

PMID- 23865873
TI  - What is your diagnosis? Lung lobe torsion.

PMID- 23865874
TI  - Diagnostic imaging in veterinary dental practice. Septic arthritis with
      Streptococcus zooepidemicus infection of the mandibular head.

PMID- 23865875
TI  - ECG of the month. Ventricular arrhythmia in a dog.

PMID- 23865876
TI  - Pathology in practice. Calcinosis cutis.

PMID- 23865877
TI  - Understanding jejunal hemorrhage syndrome.
AB  - Jejunal hemorrhage syndrome (JHS) is an acute, highly fatal enterotoxemic
      disorder in dairy cattle that has been reported during the last few decades. No
      specific cause of this syndrome has been identified; however, several studies
      have revealed a strong association between JHS and infection with Clostridium
      perfringens type A. A common mold, Aspergillus fumigatus, has also been
      implicated as a potential causative agent in this disease syndrome. Clinical
      signs of JHS (including sudden decreases in feed intake and milk production,
      rapid loss of condition, a right-sided ping audible during simultaneous
      auscultation and percussion of the abdomen, abdominal distension, and melena or
      bloody feces) usually develop early during lactation when cattle receive rations
      that are high in energy and low in fiber. Appropriate preventive strategies have
      not yet been determined, and intensive medical management with or without
      surgical intervention is rarely successful. The use of commercially available
      vaccines that are directed against C perfringens types C and D is of questionable
      efficacy and not likely to be helpful as a preventative measure. This article
      highlights the potential etiologic and risk factors, describes common clinical
      signs, outlines relevant diagnostic testing, and summarizes treatment options and
      their outcomes. 

PMID- 23865878
TI  - Evaluation of the use of serum C-reactive protein concentration to predict
      outcome in puppies infected with canine parvovirus.
AB  - OBJECTIVE: To evaluate associations of serum C-reactive protein (CRP)
      concentration with duration of hospitalization and with outcome in puppies with
      canine parvoviral enteritis. DESIGN: Prospective observational study. Animals-79
      client-owned puppies with naturally acquired canine parvovirus infection.
      PROCEDURES: All puppies received supportive care. Serum CRP concentration was
      measured at the time of admission, approximately every 10 to 12 hours for the
      first 48 hours, and then every 24 hours until discharge from the hospital or
      death. Associations between outcome and CRP concentration at various time points
      or changes in CRP concentration over time were assessed via multiple logistic
      regression. Associations of CRP concentration with survival time and duration of
      hospitalization among survivors were estimated with Cox proportional hazards
      regression. Use of CRP concentration to predict outcome was evaluated by means of
      receiver operating characteristic curve analysis. RESULTS: Serum CRP
      concentrations at admission and 12 and 24 hours later were positively associated
      with odds of death, and CRP concentrations at 12 and 24 hours after admission
      were negatively associated with survival time for puppies. Among survivors,
      duration of hospitalization was positively associated with CRP concentrations at
      12, 24, and 36 hours after admission. Sensitivity and specificity of CRP
      concentration to differentiate between survivors and nonsurvivors at 24 hours
      after admission were 86.7% and 78.7%, respectively (considered moderately
      accurate). CONCLUSIONS AND CLINICAL RELEVANCE: Although serum CRP concentration
      was associated with outcome in puppies with canine parvovirus enteritis, it did
      not prove to be a good predictor of outcome when used alone.

PMID- 23865879
TI  - Agreement between low-field MRI and CT for the detection of suspected
      intracranial lesions in dogs and cats.
AB  - OBJECTIVE: To assess the agreement between CT and MRI for enabling detection of
      intracranial lesions in cats and dogs. DESIGN: Evaluation study. ANIMALS: 51 dogs
      and 7 cats with suspected intracranial lesions. PROCEDURES: During a 2-year
      period, dogs and cats with suspected intracranial pathological changes underwent
      MRI and CT (single slice) of the head. Radiologists evaluated images produced
      with both techniques without awareness of subject identity. Agreement between
      methods was assessed for allowing detection of solitary or multiple lesions,
      selected lesion characteristics (via the Cohen kappa statistic), and lesion
      dimensions (via Bland-Altman plots). RESULTS: CT and MRI had substantial
      agreement for allowing detection of lesions and identification of whether the
      lesions were solitary or multiple. The techniques agreed almost perfectly for
      allowing identification of a mass effect and contrast medium enhancement, which
      were considered principal diagnostic imaging signs. A lower degree of agreement
      was attained for allowing identification of enhancement patterns and aspects of
      lesion margins. Agreement was substantial to almost perfect for lesion
      visualization in most anatomic brain regions but poor for identification of
      lesion dimensions. CONCLUSIONS AND CLINICAL RELEVANCE: Degrees of agreement
      between CT and MRI for allowing the detection and characterization of
      intracranial lesions ranged from poor to almost perfect, depending on the
      variable assessed. More investigation is needed into the relative analytic
      sensitivity and possible complementarities of CT and MRI in the detection of
      suspected intracranial lesions in dogs and cats.

PMID- 23865880
TI  - Comparison of ultrasonography and histologic examination for identification of
      ocular diseases of animals: 113 cases (2000-2010).
AB  - OBJECTIVE: To compare ultrasonographic and histologic examination findings for
      eyes of animals with ocular diseases. DESIGN: Retrospective case series. ANIMALS:
      116 eyes of 113 animals examined at 2 facilities. PROCEDURES: Diseased eyes of
      animals were examined by means of ultrasonography, removed via enucleation or
      exenteration, then histologically examined. Ultrasonographic images and
      histopathologic slides were evaluated, and diseases of eyes were identified with
      each of those methods and allocated to various categories. For each disease
      category, agreement between results of ultrasonography and those of histologic
      examination was assessed via determination of kappa statistic values. RESULTS:
      Tests had good agreement for identification of iris or ciliary body neoplasia.
      Overall, intraocular neoplasia was not detected via ultrasonography for only 2 of
      31 eyes with histologically detected neoplasia. Hemorrhagic or inflammatory
      changes were misinterpreted as neoplasia for 8 of 37 (22%) eyes. Tests had
      moderate to acceptable agreement for identification of retinal detachment.
      Retinal detachment was not detected by means of ultrasonography for 14 of 38
      (37%) eyes with that diagnosis determined via histologic examination at one of
      the facilities (primarily in eyes with intraocular hemorrhage); however, retinal
      detachment was not identified via histologic examination for 6 of 38 (16%) eyes
      with that diagnosis determined via ultrasonography at the other facility.
      CONCLUSIONS AND CLINICAL RELEVANCE: Agreement between tests evaluated in this
      study was clinically satisfactory for identification of intraocular neoplasia.
      Typically, diseases were misdiagnosed via ultrasonography for eyes with poor
      image contrast. Because determination of ultrasonographic diagnoses of retinal
      detachment and intraocular neoplasm may be of prognostic importance, performance
      of additional ultrasonographic techniques may be indicated.

PMID- 23865881
TI  - Mineral composition of urinary calculi from potbellied pigs with urolithiasis: 50
      cases (1982-2012).
AB  - OBJECTIVE: To determine the mineral composition and anatomic location of urinary
      calculi and to investigate sex and reproductive status as predisposing factors
      for development of urolithiasis in potbellied pigs. DESIGN: Retrospective case
      series SAMPLES: Urinary calculi from 50 purebred and crossbred potbellied pigs.
      PROCEDURES: Laboratory records for urinary calculi of potbellied pigs submitted
      to the University of California-Davis Stone Laboratory from 1982 through 2012
      were reviewed. Mineral composition of calculi was determined by polarized light
      microscopy, infrared spectroscopy, and, in some cases, x-ray diffractometry.
      RESULTS: Of the 48 urinary calculi analyzed by infrared spectroscopy, 21 (44%)
      were composed primarily of amorphous magnesium calcium phosphate; another 9 (19%)
      were primarily composed of calcium phosphate in the form of apatite. Of 50
      urinary calculi, 22 (44%), 14 (28%), 10 (20%), 3 (6%), and 1 (2%) were removed
      from the urinary bladder only, urethra, both urinary bladder and urethra, urine,
      and renal pelvis, respectively. Sex of 6 potbellied pigs was not recorded. For 44
      urinary calculi, 41 (93%) were from males (11 sexually intact males and 30
      castrated) and 3 (7%) were from females (2 sexually intact females and 1 spayed).
      Among males, 73% (30/41) of submissions were from castrated males. CONCLUSIONS
      AND CLINICAL RELEVANCE: In contrast to results from studies in commercial pigs,
      the most common composition of urinary calculi identified in purebred and
      crossbred potbellied pigs was amorphous magnesium calcium phosphate. Potential
      predisposing factors for urolithiasis in potbellied pigs may be similar to those
      for urolithiasis in commercial pigs. These include diet, urinary tract
      infections, and sex. Thus, prevention of urolithiasis should target these
      potential predisposing factors.

PMID- 23865882
TI  - Arterial thrombosis after vehicular trauma and humeral fracture in a dog.
AB  - CASE DESCRIPTION: A 3-year-old 19-kg (42-lb) spayed female mixed-breed dog was
      referred after being hit by a car. Injuries included pneumothorax, hemothorax,
      pulmonary contusions, a full-thickness axillary skin wound, and a grade I
      transverse fracture of the midshaft of the right humerus. Following patient
      stabilization, open reduction and internal fixation of the fracture were
      performed. The dog had weight-bearing lameness at the time of discharge. Eight
      days after fracture repair, the dog was reevaluated for acute onset of signs of
      pain and non-weight-bearing lameness in the right forelimb. CLINICAL FINDINGS:
      Physical examination findings in the right forelimb (knuckling and coolness, with
      absent digital pulses) were suggestive of a thrombus. Ultrasonography confirmed a
      right brachial artery thrombus with minimal blood flow to the affected limb.
      TREATMENT AND OUTCOME: Unfractionated heparin was administered via continuous IV
      infusion for the first 36 hours of hospitalization. Clopidogrel administration
      was also started at this time. During hospitalization, rapid clinical improvement
      occurred, and the dog was discharged 48 hours after admission. The transition to
      outpatient therapy was achieved by discontinuation of the unfractionated heparin
      infusion at 36 hours and beginning SC administration of dalteparin. Outpatient
      treatment with dalteparin and clopidogrel was continued. Repeated physical
      examination and ultrasonography 5 weeks later revealed resolution of the thrombus
      and normal blood flow to the limb. Anticoagulant administration was discontinued
      at that time. CLINICAL RELEVANCE: Thrombosis should be suspected in any dog with
      signs of acute pain after severe trauma or fracture repair, with or without
      concurrent lameness, that do not resolve with appropriate treatment. Restoration
      of blood flow to the affected limb after initiation of unfractionated heparin and
      clopidogrel administration followed by outpatient treatment with dalteparin and
      clopidogrel was achieved in this case.

PMID- 23865883
TI  - Validation of a low-dose adrenocorticotropic hormone stimulation test in healthy
      neonatal foals.
AB  - OBJECTIVE: To determine the lowest ACTH dose that would induce a significant
      increase in serum cortisol concentration and identify the time to peak cortisol
      concentration in healthy neonatal foals. DESIGN: Prospective randomized crossover
      study. ANIMALS: 11 healthy neonatal foals. PROCEDURES: Saline (0.9% NaCl)
      solution or 1 of 4 doses (0.02, 0.1, 0.25, and 0.5 MUg/kg [0.009, 0.045, 0.114,
      and 0.227 MUg/lb]) of cosyntropin (synthetic ACTH) was administered IV. Serum
      cortisol concentrations were measured before and 10, 20, 30, 60, 90, 120, 180,
      and 240 minutes after administration of cosyntropin or saline solution; CBCs were
      performed before and 30, 60, 120, and 240 minutes after administration. RESULTS:
      Serum cortisol concentration was significantly increased, compared with baseline,
      by 10 minutes after cosyntropin administration at doses of 0.1, 0.25, and 0.5
      MUg/kg. Serum cortisol concentration peaked 20 minutes after administration of
      cosyntropin at doses of 0.02, 0.1, and 0.25 MUg/kg, with peak concentrations 1.7,
      2.0, and 1.9 times the baseline concentration, respectively. Serum cortisol
      concentration peaked 30 minutes after cosyntropin administration at a dose of 0.5
      MUg/kg, with peak concentration 2.2 times the baseline concentration. No
      significant differences were detected among peak serum cortisol concentrations
      obtained with cosyntropin administration at doses of 0.25 and 0.5 MUg/kg.
      Cosyntropin administration significantly affected the lymphocyte count and the
      neutrophil-to-lymphocyte ratio. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that in healthy neonatal foals, the lowest dose of cosyntropin to
      result in significant adrenal gland stimulation was 0.25 MUg/kg, with peak
      cortisol concentration 20 minutes after cosyntropin administration.

PMID- 23865884
TI  - Evaluation of survival rate and athletic ability after nonsurgical or surgical
      treatment of cleft palate in horses: 55 cases (1986-2008).
AB  - OBJECTIVE: To determine survival rate and athletic ability after nonsurgical or
      surgical treatment of cleft palate in horses. DESIGN: Retrospective case series.
      ANIMALS: 55 horses with cleft palate. PROCEDURES: 13 of the 55 horses died or
      were euthanized without treatment and were not included in all analyses. Medical
      records were reviewed for signalment, history, method of diagnosis, soft or hard
      palate involvement, type of surgical procedure performed, postoperative
      complications, and survival to hospital discharge. Information on athletic
      ability was acquired from race records and follow-up conversations with owners,
      trainers, or referring veterinarians. RESULTS: The predominant reason for initial
      evaluation was milk or feed in the nostrils (60%). The diagnosis was confirmed by
      means of videoendoscopy of the upper portion of the airway in all cases. Most
      cases involved the soft palate only (92.7%). Twenty-six of the 55 (47.3%) horses
      underwent surgical repair, and 12 of these had dehiscence at the caudal edge of
      the soft palate. Among potential racehorses, 14 of 33 had surgery. Of these, 12
      of 14 survived to discharge and 2 horses raced. Among potential racehorses, 10 of
      33 were discharged without surgery and 2 of these raced. Among nonracehorses, 12
      of 22 underwent surgery and 11 survived to discharge. All horses that were
      discharged and for which follow-up information was available survived to 2 years
      of age or older without ill thrift despite dehiscence at the caudal edge of the
      soft palate and continued mild nasal discharge. CONCLUSIONS AND CLINICAL
      RELEVANCE: Horses with cleft palate had a higher survival rate than previously
      reported.

PMID- 23865885
TI  - Development of a model to simulate infection dynamics of Mycobacterium bovis in
      cattle herds in the United States.
AB  - OBJECTIVE: To develop a mathematical model to simulate infection dynamics of
      Mycobacterium bovis in cattle herds in the United States and predict efficacy of
      the current national control strategy for tuberculosis in cattle. DESIGN:
      Stochastic simulation model. SAMPLE: Theoretical cattle herds in the United
      States. PROCEDURES: A model of within-herd M bovis transmission dynamics
      following introduction of 1 latently infected cow was developed. Frequency- and
      density-dependent transmission modes and 3 tuberculin test-based culling
      strategies (no test-based culling, constant [annual] testing with test-based
      culling, and the current strategy of slaughterhouse detection-based testing and
      culling) were investigated. Results were evaluated for 3 herd sizes over a 10
      year period and validated via simulation of known outbreaks of M bovis infection.
      RESULTS: On the basis of 1,000 simulations (1,000 herds each) at replacement
      rates typical for dairy cattle (0.33/y), median time to detection of M bovis
      infection in medium-sized herds (276 adult cattle) via slaughterhouse
      surveillance was 27 months after introduction, and 58% of these herds would
      spontaneously clear the infection prior to that time. Sixty-two percent of medium
      sized herds without intervention and 99% of those managed with constant test
      based culling were predicted to clear infection < 10 years after introduction.
      The model predicted observed outbreaks best for frequency-dependent transmission,
      and probability of clearance was most sensitive to replacement rate. CONCLUSIONS
      AND CLINICAL RELEVANCE: Although modeling indicated the current national control
      strategy was sufficient for elimination of M bovis infection from dairy herds
      after detection, slaughterhouse surveillance was not sufficient to detect M bovis
      infection in all herds and resulted in subjectively delayed detection, compared
      with the constant testing method. Further research is required to economically
      optimize this strategy.

PMID- 23865886
TI  - Pharmacokinetics and distribution of ceftazidime to milk after intravenous and
      intramuscular administration to lactating female dromedary camels (Camelus
      dromedarius).
AB  - OBJECTIVE: To determine the plasma disposition kinetics, absolute
      bioavailability, and milk concentrations of ceftazidime in healthy lactating
      female dromedary camels (Camelus dromedarius) following IV and IM administration
      of a single dose of 10 mg/kg (4.5 mg/lb). DESIGN: Prospective crossover study.
      ANIMALS: 8 healthy adult lactating female dromedary camels. PROCEDURES: Camels
      received ceftazidime (10 mg/kg) IV and IM in a crossover study design with a 15
      day washout period between treatments. Plasma and milk samples were collected at
      predetermined times for 48 hours after drug administration and analyzed by use of
      high-performance liquid chromatography. RESULTS: A 2-compartment open model best
      represented the plasma concentration-versus-time data after IV and IM
      administration of ceftazidime to camels. Plasma ceftazidime concentrations
      decreased biexponentially after IV administration with mean distribution and
      elimination half-lives of 0.3 hours and 2.85 hours, respectively. After IM
      administration, the mean maximum plasma concentration of ceftazidime was 32.43
      MUg/mL (1.21 hours after administration), mean elimination half-life was 3.20
      hours, mean residence time was 4.84 hours, and mean systemic bioavailability was
      93.72%. Distribution of ceftazidime from plasma to milk was rapid and extensive
      as indicated by the ratio of the area under the milk concentration-versus-time
      curve to the area under the plasma concentration-versus-time curve and the ratio
      of the maximum milk concentration to the maximum plasma concentration of
      ceftazidime after IV and IM administration. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggested that ceftazidime may be a useful treatment for female camels
      with mastitis caused by susceptible microorganisms.

PMID- 23865887
TI  - Osseous sequestration in alpacas and llamas: 36 cases (1999-2010).
AB  - OBJECTIVE: To describe clinical findings, treatments, and outcome in camelids
      treated for osseous sequestration. DESIGN: Retrospective case series. ANIMALS: 27
      alpacas and 9 llamas with osseous sequestration. PROCEDURES: Medical records of 2
      veterinary teaching hospitals were reviewed to identify camelids evaluated
      because of osseous sequestration between January 1, 1999, and December 31, 2010.
      Data on history, signalment, physical examination and medical imaging findings,
      treatment, and complications were collected. RESULTS: Records of 36 camelids were
      included, of which there were 22 sexually intact males, 11 females, and 2
      castrated males with a median age of 7. 5 months, 3.9 months, and 8.5 years,
      respectively (age and sex were not available for 1 camelid). The most common
      clinical signs were lameness, swelling over the affected bone, and associated
      draining sinus. Sequestra were associated with trauma in 7 (19%) camelids.
      Camelids with sequestra not associated with trauma (n = 29 [81%]) were
      significantly younger than those with sequestra attributed to trauma. Thirty-four
      camelids underwent sequestrectomy, and all survived to hospital discharge (median
      duration of hospitalization, 6.5 days). Recurrence of a sequestrum occurred twice
      in 1 (3%) camelid. Long-term follow-up (>= 12 months) information was available
      on 24 camelids, of which 20 (83%) recovered without long-term complications.
      CONCLUSIONS AND CLINICAL RELEVANCE: Unlike in other livestock, trauma was not a
      primary cause of osseous sequestration in camelids. Sequestra should be
      considered in the differential diagnostic process in camelids with lameness, a
      draining sinus, or a firm swelling over a bony prominence. Sequestrectomy is a
      successful treatment option.

PMID- 23865888
TI  - The new species Enterobacter oryziphilus sp. nov. and Enterobacter
      oryzendophyticus sp. nov. are key inhabitants of the endosphere of rice.
AB  - BACKGROUND: Six independent Gram-negative, facultatively anaerobic, non-spore
      forming, nitrogen-fixing rod-shaped isolates were obtained from the root
      endosphere of rice grown at the International Rice Research Institute (IRRI) and
      investigated in a polyphasic taxonomic study. RESULTS: The strains produced fatty
      acid patterns typical for members of the family Enterobacteriaceae. Comparative
      sequence analyses of the 16S rRNA as well as rpoB genes allocated the strains to
      two well-defined groups within the genus Enterobacter, family Enterobacteriaceae.
      The analyses indicated Enterobacter radicincitans, Enterobacter arachidis and
      Enterobacter oryzae to be the closest related species. An RpoB (translated)
      protein comparison supported the placement in the genus Enterobacter and the
      relatedness of our isolates to the aforementioned species. Genomic DNA:DNA
      hybridization analyses and biochemical analyses provided further evidence that
      the novel strains belong to two new species within the genus Enterobacter. The
      two species can be differentiated from each other and from existing enteric
      species by acid production from L-rhamnose and D-melibiose, decarboxylation of
      ornithine and utilization of D-alanine, D-raffinose L-proline and L-aspartic
      acid, among other characteristics. Members of both species revealed capacities to
      colonise rice roots, including plant-growth-promoting capabilities such as an
      active supply of fixed nitrogen to the plant and solubilisation of inorganic
      phosphorus, next to traits allowing adaptation to the plant. CONCLUSIONS: Two
      novel proposed enterobacterial species, denominated Enterobacter oryziphilus sp.
      nov. (type strain REICA_142(T)=LMG 26429(T)=NCCB 100393(T)) and Enterobacter
      oryzendophyticus sp. nov. (type strain REICA_082(T)=LMG 26432(T) =NCCB 100390(T))
      were isolated from rice roots. Both species are capable of promoting rice growth
      by supplying nitrogen and phosphorus.

PMID- 23865889
TI  - Formation of nitro-PAHs from the heterogeneous reaction of ambient particle-bound
      PAHs with N2O5/NO3/NO2.
AB  - Reactions of ambient particles collected from four sites within the Los Angeles,
      CA air basin and Beijing, China with a mixture of N2O5, NO2, and NO3 radicals
      were studied in an environmental chamber at ambient pressure and temperature.
      Exposures in the chamber system resulted in the degradation of particle-bound
      PAHs and formation of molecular weight (mw) 247 nitropyrenes (NPYs) and
      nitrofluoranthenes (NFLs), mw 273 nitrotriphenylenes (NTPs),
      nitrobenz[a]anthracenes (NBaAs), nitrochrysene (NCHR), and mw 297
      nitrobenzo[a]pyrene (NBaP). The distinct isomer distributions resulting from
      exposure of filter-adsorbed deuterated fluoranthene to N2O5/NO3/NO2 and that
      collected from the chamber gas-phase suggest that formation of NFLs in ambient
      particles did not occur by NO3 radical-initiated reaction but from reaction of
      N2O5, presumably subsequent to its surface adsorption. Accordingly, isomers known
      to result from gas-phase radical-initiated reactions of parent PAHs, such as 2
      NFL and 2- and 4-NPY, were not enhanced from the exposure of ambient particulate
      matter to N2O5/NO3/NO2. The reactivity of ambient particles toward nitration by
      N2O5/NO3/NO2, defined by relative 1-NPY formation, varied significantly, with the
      relative amounts of freshly emitted particles versus aged particles (particles
      that had undergone atmospheric chemical processing) affecting the reactivity of
      particle-bound PAHs toward heterogeneous nitration. Analyses of unexposed ambient
      samples suggested that, in nighttime samples where NO3 radical-initiated
      chemistry had occurred, heterogeneous formation of 1-NPY on ambient particles may
      have contributed to the ambient 1-NPY concentrations at downwind receptor sites.
      These results, together with observations that 2-NFL is consistently the dominant
      particle-bound nitro-PAH measured in ambient atmospheres, suggest that for PAHs
      that exist in both the gas- and particle-phase, the heterogeneous formation of
      particle-bound nitro-PAHs is a minor formation route compared to gas-phase
      formation. 

PMID- 23865890
TI  - Design and characterization of molecular nonlinear optical switches.
AB  - Nanoscale structures, including molecules, supramolecules, polymers,
      functionalized surfaces, and crystalline/amorphous solids, can commute between
      two or more forms, displaying contrasts in their nonlinear optical (NLO)
      properties. Because of this property, they have high potential for applications
      in data storage, signal processing, and sensing. As potential candidates for
      integration into responsive materials, scientists have been intensely studying
      organic and organometallic molecules with switchable first hyperpolarizability
      over the past two decades. As a result of this, researchers have been able to
      synthesize and characterize several families of molecular NLO switches that
      differ by the stimulus used to trigger the commutation. These stimuli can include
      light irradiation, pH variation, redox reaction, and ion recognition, among
      others. The design of multistate (including several switchable units) and
      multifunctional (triggered with different stimuli) systems has also motivated a
      large amount of work, aiming at the improvement of the storage capacity of
      optical memories or the diversification of the addressability of the devices. In
      complement to the synthesis of the compounds and the characterization of their
      NLO responses by means of hyper-Rayleigh scattering, quantum chemical
      calculations play a key role in the design of molecular switches with high first
      hyperpolarizability contrasts. Through the latter, we can gain a fundamental
      understanding of the various factors governing the efficiency of the switches.
      These are not easily accessible experimentally, and include donor/acceptor
      contributions, frequency dispersion, and solvent effects. In this Account, we
      illustrate the similarities of the experimental and theoretical tools to design
      and characterize highly efficient NLO switches but also the difficulties in
      comparing them. After providing a critical overview of the different theoretical
      approaches used for evaluating the first hyperpolarizabilities, we report two
      case studies in which theoretical simulations have provided guidelines to design
      NLO switches with improved efficiencies. The first example presents the joint
      theoretical/experimental characterization of a new family of multi-addressable
      NLO switches based on benzazolo-oxazolidine derivatives. The second focuses on
      the photoinduced commutation in merocyanine-spiropyran systems, where the
      significant NLO contrast could be exploited for metal cation identification in a
      new generation of multiusage sensing devices. Finally, we illustrate the impact
      of environment on the NLO switching properties, with examples based on the keto
      enol equilibrium in anil derivatives. Through these representative examples, we
      demonstrate that the rational design of molecular NLO switches, which combines
      experimental and theoretical approaches, has reached maturity. Future challenges
      consist in extending the investigated objects to supramolecular architectures
      involving several NLO-responsive units, in order to exploit their cooperative
      effects for enhancing the NLO responses and contrasts. 

PMID- 23865891
TI  - Getting up to speed with the public health and regulatory challenges posed by new
      psychoactive substances in the information age.

PMID- 23865892
TI  - Oral health assessment in the San Blas and Santa Ana populations of Nicaragua.
AB  - AIM: The aim of this study was to assess the oral health of a population in rural
      Nicaragua. METHODS: A total of 241 individuals were recruited from areas around
      San Blas and Santa Ana, Nicaragua. A demographic questionnaire assessing income,
      access to oral health care, means of transportation and presence of dental/health
      insurance was collected for each patient. Oral screenings were also conducted to
      assess for evidence of untreated decayed teeth, restorations, missing/extracted
      teeth and presence/absence of periodontal disease. RESULTS: The majority of
      residents in San Blas and Santa Ana, Nicaragua, have little income if any, no
      medical or dental insurance of any kind and no means of transportation. There was
      a very high prevalence of untreated decayed teeth among the population studied
      where 51.1% of our sample had three or more dental caries. Children aged fewer
      than 20 years had five times the prevalence of dental decay than those in the
      United States. No statistically significant difference was found in untreated
      decayed teeth by age or gender. A smaller percentage (25.2%) of all patients had
      restorations with a statistically significant difference found between genders (P
      < 0.0001). There was also a relationship between gender and number of
      missing/extracted teeth (P < 0.001). There was no significant difference in
      amount of untreated decayed teeth among those who reported having been seen by a
      dentist within the previous one-to-three, greater than 3 years or never at all.
      CONCLUSION: Among a population of individuals from San Blas and Santa Ana,
      Nicaragua, there are major socio-economic barriers present, and a significant
      burden of oral pathology is evident.

PMID- 23865893
TI  - Haem catabolism: a novel modulator of inflammation in Gilbert's syndrome.
AB  - BACKGROUND: Moderately elevated unconjugated bilirubin concentrations protect
      against inflammatory diseases and are present in individuals with Gilbert's
      syndrome. This study examined the relationship between circulating haem oxygenase
      catabolites, unconjugated bilirubin, carboxy haemoglobin, iron and inflammatory
      parameters. MATERIALS AND METHODS: Seventy-six matched individuals were allocated
      to Gilbert's syndrome (GS) or control group (unconjugated bilirubin >= or < 17.1
      MUM). Iron, carboxy haemoglobin and high-sensitivity C-reactive protein were
      analysed using routine diagnostic tests. Unconjugated bilirubin and haem were
      analysed using high-performance liquid chromatography. The cytokines IL-1beta,
      TNF-alpha and IL-6 were assessed using high-sensitivity enzyme-linked
      immunosorbent assays. RESULTS: Gilbert's syndrome subjects had significantly
      greater levels of unconjugated bilirubin (P < 0.05), carboxy haemoglobin (P <
      0.05), iron (P < 0.05), IL-1beta (P < 0.05), a significantly lower body mass
      index (P < 0.05) and IL-6 concentrations (P < 0.05) vs. controls. Regression
      analysis revealed that unconjugated bilirubin mainly explained IL-1beta results
      (16%), and body mass index+IL-6 predicted 26% of the variance in C-reactive
      protein concentrations. CONCLUSIONS: A positive relationship between unconjugated
      bilirubin and free plasma haem, iron and carboxy haemoglobin indicated a positive
      feedback loop of haem oxygenase induction possibly mediated by unconjugated
      bilirubin. Furthermore, reduced body mass index in Gilbert's syndrome individuals
      was linked to reduced inflammation status, which could be influenced by
      circulating haem oxygenase catabolites and contribute to reduced risk of
      noncommunicable diseases in this population.

PMID- 23865894
TI  - Direct and diastereoselective alkylation and aldol reactions of alpha-bromo-alpha
      fluoro-beta-lactams.
AB  - Herein, we describe the development of a method for the direct alkylation and
      aldol reaction of alpha-bromo-alpha-fluoro-beta-lactams. This method provides
      facile access to a wide range of 3-alkyl- and 3-hydroxyalkyl-fluoro-beta-lactams
      in good yields under mild conditions. The products were obtained with complete
      diastereoselectivity with regard to the relative configuration of the beta-lactam
      ring at C3 and C4 positions. The reaction conditions were tolerant of a broad
      range of electrophiles, which highlights the overall scope and utility of this
      procedure. 

PMID- 23865895
TI  - Social systems and life-history characteristics of mongooses.
AB  - The diversity of extant carnivores provides valuable opportunities for
      comparative research to illuminate general patterns of mammalian social
      evolution. Recent field studies on mongooses (Herpestidae), in particular, have
      generated detailed behavioural and demographic data allowing tests of assumptions
      and predictions of theories of social evolution. The first studies of the social
      systems of their closest relatives, the Malagasy Eupleridae, also have been
      initiated. The literature on mongooses was last reviewed over 25 years ago. In
      this review, we summarise the current state of knowledge on the social
      organisation, mating systems and social structure (especially competition and
      cooperation) of the two mongoose families. Our second aim is to evaluate the
      contributions of these studies to a better understanding of mammalian social
      evolution in general. Based on published reports or anecdotal information, we can
      classify 16 of the 34 species of Herpestidae as solitary and nine as group
      living; there are insufficient data available for the remainder. There is a
      strong phylogenetic signal of sociality with permanent complex groups being
      limited to the genera Crossarchus, Helogale, Liberiictis, Mungos, and Suricata.
      Our review also indicates that studies of solitary and social mongooses have been
      conducted within different theoretical frameworks: whereas solitary species and
      transitions to gregariousness have been mainly investigated in relation to
      ecological determinants, the study of social patterns of highly social mongooses
      has instead been based on reproductive skew theory. In some group-living species,
      group size and composition were found to determine reproductive competition and
      cooperative breeding through group augmentation. Infanticide risk and inbreeding
      avoidance connect social organisation and social structure with reproductive
      tactics and life histories, but their specific impact on mongoose sociality is
      still difficult to evaluate. However, the level of reproductive skew in social
      mongooses is not only determined by the costs and benefits of suppressing each
      other's breeding attempts, but also influenced by resource abundance. Thus,
      dispersal, as a consequence of eviction, is also linked to the costs of co
      breeding in the context of food competition. By linking these facts, we show that
      the socio-ecological model and reproductive skew theory share some determinants
      of social patterns. We also conclude that due to their long bio-geographical
      isolation and divergent selection pressures, future studies of the social systems
      of the Eupleridae will be of great value for the elucidation of general patterns
      in carnivore social evolution. 

PMID- 23865896
TI  - New York State TrueAllele (r) casework validation study.
AB  - DNA evidence can pose interpretation challenges, particularly with low-level or
      mixed samples. It would be desirable to make full use of the quantitative data,
      consider every genotype possibility, and objectively produce accurate and
      reproducible DNA match results. Probabilistic genotype computing is designed to
      achieve these goals. This validation study assessed TrueAllele((r)) probabilistic
      computer interpretation on 368 evidence items in 41 test cases and compared the
      results with human review of the same data. Whenever there was a human result,
      the computer's genotype was concordant. Further, the computer produced a match
      statistic on 81 mixture items (for 87 inferred matching genotypes) in the test
      cases, while human review reported a statistic on 25 of these items (30.9%).
      Using match statistics to quantify information, probabilistic genotyping was
      shown to be sensitive, specific, and reproducible. These results demonstrate that
      objective probabilistic genotyping of biological evidence can reliably preserve
      DNA identification information. 

PMID- 23865897
TI  - Classification of protein motifs based on subcellular localization uncovers
      evolutionary relationships at both sequence and functional levels.
AB  - BACKGROUND: Most proteins have evolved in specific cellular compartments that
      limit their functions and potential interactions. On the other hand, motifs
      define amino acid arrangements conserved between protein family members and
      represent powerful tools for assigning function to protein sequences. The ideal
      motif would identify all members of a protein family but in practice many motifs
      identify both family members and unrelated proteins, referred to as True Positive
      (TP) and False Positive (FP) sequences, respectively. RESULTS: To address the
      relationship between protein motifs, protein function and cellular localization,
      we systematically assigned subcellular localization data to motif sequences from
      the comprehensive PROSITE sequence motif database. Using this data we analyzed
      relationships between localization and function. We find that TPs and FPs have a
      strong tendency to localize in different compartments. When multiple
      localizations are considered, TPs are usually distributed between related
      cellular compartments. We also identified cases where FPs are concentrated in
      particular subcellular regions, indicating possible functional or evolutionary
      relationships with TP sequences of the same motif. CONCLUSIONS: Our findings
      suggest that the systematic examination of subcellular localization has the
      potential to uncover evolutionary and functional relationships between motif
      containing sequences. We believe that this type of analysis complements existing
      motif annotations and could aid in their interpretation. Our results shed light
      on the evolution of cellular organelles and potentially establish the basis for
      new subcellular localization and function prediction algorithms.

PMID- 23865898
TI  - Improvement of quality of life in methadone treatment patients in northern
      Taiwan: a follow-up study.
AB  - BACKGROUND: This study examined long-term improvement of quality of life amongst
      heroin users enrolled in methadone maintenance treatment (MMT). METHODS: The
      sample contained 553 heroin-dependent individuals from 4 hospitals in northern
      Taiwan who enrolled in MMT for an average of 184 days. Each patient signed a
      consent form and was assessed prospectively 3 times semi-annually. Quality of
      life was measured using the WHOQOL-BREF questionnaire, 26 items of which were
      scored by the participants. The WHOQOL-BREF consists of four domains: physical,
      psychological, social, and environmental. 285 and 155 participants completed 6
      month and 12-month follow-ups respectively. RESULTS: After controlling for
      demographic and clinical characteristics, there were statistically significant
      improvements in the psychological and environmental domains between baseline and
      6 months. Significant improvements were found in psychological and social domains
      between baseline and 12 months. CONCLUSIONS: It is concluded that methadone
      maintenance treatment improves heroin users' long-term quality of life in the
      psychological and social relationship domains.

PMID- 23865899
TI  - Hypoxia induces osteogenesis in rabbit adipose-derived stem cells overexpressing
      bone morphogenic protein-2.
AB  - OBJECTIVE: Hypoxic culture potentiates mesenchymal stem cells (MSCs) to survive
      and secrete various growth factors. Genetically modified stem cells
      overexpressing bone morphogenic protein-2 (BMP-2) demonstrate strong osteogenic
      ability. Hence, we investigated the coeffect of hypoxic culture conditions and
      BMP-2 overexpression on the osteogenic ability of rabbit adipose-derived stem
      cells (rASCs) in vitro. MATERIALS AND METHODS: Rabbit adipose-derived stem cells
      with or without adenoviral-BMP-2 transduction were cultured in hypoxic (1%) and
      normoxic (21%) conditions. Cell viability, attachment, and proliferation were
      compared. Real-time PCR amplification of osteogenic and angiogenic genes
      including alkaline phosphatase (ALP), osteocalcin (OCN), HIF-1alpha, and vascular
      endothelial growth factor (VEGF) was performed. Moreover, ALP activity,
      immunofluorescent staining of OCN, and mineralization assay by alizarin red S
      quantification and von Kossa staining were conducted. RESULTS: Cells under
      hypoxic conditions attached better within 12 h and proliferated faster. While BMP
      2 overexpression and hypoxic condition separately elevated the transcription of
      key osteogenic and angiogenic genes, a cooperative effect was observed to enhance
      the upregulation of osteogenic as well as angiogenic genes. Identical changes
      were observed in ALP activity, immunofluorescent staining of OCN, and
      mineralization assay. CONCLUSIONS: Hypoxic culture can enhance the osteogenic
      ability of BMP-2 gene-modified rASCs, which provides a strategy to improve the
      osteogenesis of rASCs for in vivo bone regeneration.

PMID- 23865900
TI  - Complications and morbidity following breast reconstruction--a review of 16,063
      cases from the 2005-2010 NSQIP datasets.
AB  - Post-operative complications pose a significant set-back for patients undergoing
      breast reconstruction. This study aims to characterize factors associated with
      postoperative complications following breast reconstruction using the National
      Surgical Quality Improvement Program (ACS-NSQIP) database from 2005-2010. The
      2005-2010 ACS-NSQIP databases were reviewed, identifying encounters for CPT codes
      including either implant-based reconstruction (immediate, delayed, and tissue
      expander) or autologous reconstruction (pedicled transverse rectus abdominus
      myocutaneous (TRAM), free TRAM, and latissimus dorsi flap with or without
      implant). Complications were characterized into three categories: major surgical
      complications, wound complications, and medical complications. During the study
      period 16,063 breast reconstructions were performed. Autologous reconstructions
      were performed in 20.7% of patients and implant-based in 79.3%. The incidence of
      major surgical complications was 8.4%, whereas the incidence of medical and wound
      complications was 1.6% and 3.5%, respectively. Independent risk factors for major
      surgical complications included: immediate and autologous reconstructions,
      obesity, smoking, previous percutaneous cardiac surgery (PCS), recent weight
      loss, bleeding disorder, recent surgery, ASA >= 3, intra-operative transfusion,
      and prolonged operative times. Risk factors for medical complications included:
      autologous reconstruction, obesity, tumor involving CNS, bleeding disorders,
      recent surgery, ASA >= 3, intra-operative transfusion, and prolonged operative
      times. This study characterizes the incidence of surgical and medical
      complications following breast reconstruction using a large, prospective
      multicentre dataset. Key identifiable risk factors associated with both surgical
      and medical morbidity included: autologous breast reconstruction, obesity, ASA >=
      3, bleeding disorders, and prolonged operative time. Data derived from this
      cohort can be used to risk-stratify patients and to enhance perioperative
      decision-making.

PMID- 23865901
TI  - Palladium(II)-catalyzed direct carboxylation of alkenyl C-H bonds with CO2.
AB  - Pd-catalyzed direct carboxylation of alkenyl C-H bonds with carbon dioxide was
      realized for the first time. Treatment of 2-hydroxystyrenes and a catalytic
      amount of Pd(OAc)2 with Cs2CO3 under atmospheric pressure of CO2 afforded
      corresponding coumarins in good yield. Furthermore, isolation of the key
      alkenylpalladium intermediate via C-H bond cleavage was achieved. The reaction
      was proposed to undergo reversible nucleophilic addition of the alkenylpalladium
      intermediate to CO2. 

PMID- 23865902
TI  - Prevention of seroma formation after axillary dissection--a comparative
      randomized clinical trial of three methods.
AB  - Seroma is a frequent complication after breast cancer surgery. Closed suction
      drainage for several days is the standard procedure to reduce seroma formation.
      The aim of this study was to compare the efficacy of external compression
      dressing, suture flap fixation, and the conventional method of closed suction
      drains in the prevention of seroma formation. A total of 161 patients were
      prospectively randomized in a three groups * two subgroups design into control (n
      = 48), compression dressing (n = 53) and suturing groups (n = 49), and two
      subgroups, conventional drain removal (n = 75) and early drain removal (n = 75).
      All patients underwent ALND as part of MRM or BCT. The primary end point was the
      incidence of seroma. Suture flap fixation significantly reduced the incidence of
      seroma (p = 0.003), total drain output (p = 0.005), and duration of drainage (p =
      0.001) without increase in wound complications. Compression dressing reduced
      duration of drainage significantly (p = 0.03), but not the total drain output (p
      = 0.15) or seromas (p = 0.58). Early drain removal on postoperative day 7
      irrespective of drain output does not significantly increase seroma formation (p
      = 0.34) or wound complications. On multivariate analysis, BMI >= 30 (p = 0.02)
      and longer duration of drainage (p = 0.04) were identified as independent
      predictors for seroma formation. Obliteration of the dead space after breast
      cancer surgery by suture flap fixation is a safe and easy procedure, which
      significantly reduces postoperative seroma formation and duration of drainage.
      Compression dressing offers no advantage over normal dressing. Drains can be
      removed safely on postoperative day 7 irrespective of output without significant
      increase in complications.

PMID- 23865903
TI  - Autonomy and social norms in a three factor grief model predicting perinatal
      grief in India.
AB  - Perinatal grief following stillbirth is a significant social and mental health
      burden. We examined associations among the following latent variables: autonomy,
      social norms, self-despair, strained coping, and acute grief-among poor, rural
      women in India who experienced stillbirth. A structural equation model was built
      and tested using quantitative data from 347 women of reproductive age in
      Chhattisgarh. Maternal acceptance of traditional social norms worsens self
      despair and strained coping, and increases the autonomy granted to women. Greater
      autonomy increases acute grief. Greater despair and acute grief increase strained
      coping. Social and cultural factors were found to predict perinatal grief in
      India. 

PMID- 23865904
TI  - Typing of Pneumocystis jirovecii isolates from Iranian immunosuppressed patients
      based on the Internal Transcribed Spacer (ITS) region of the rRNA gene.
AB  - Since there have been no published molecular studies of Pneumocystis jirovecii
      isolates from Iranian patients, we investigated the genotypes of such isolates
      recovered from HIV-infected patients, those undergoing cancer chemotherapy and
      patients with chronic obstructive pulmonary disease (COPD). P. jirovecii typing,
      based on ITS1 and ITS2 sequence analysis, was performed on 34 isolates from
      Iranian immunosuppressed patients. In total, 44 genotypes were detected of which
      relative to ITS1, eight known genotypes (A, B, C, E, G, H, N and O) and one novel
      sequence were noted. Eight known genotypes (b, c, e, g, h, i, j and n) were also
      found with ITS2. The most frequent ITS1 and ITS2 genotypes were E (21/44, 47.7%)
      and g (22/44, 50%), respectively. From determined haplotypes, the four most
      frequent ones were Eg (11/44, 25%), Gg (5/44, 11.3%), Gi (4/44, 9.1%), Ei (3/44,
      6.8%), and Hg (3/44, 6.8%). Two novel haplotypes (Hb and Hi) were also
      identified, along with mixed infections as seven (20.5%) patients were found to
      have more than one haplotype. It is suggested that novel haplotypes in Iranian
      patients may be generated through sexual recombination within the host.

PMID- 23865906
TI  - Magnocellular neurosecretory neurones: a review by consensus!

PMID- 23865905
TI  - Changes in alcohol intake and their relationship with health status over a 24
      year follow-up period in community-dwelling older adults.
AB  - OBJECTIVES: To determine whether alcohol use changes over time in older adults
      and whether alcohol intake is associated with common chronic diseases. DESIGN:
      Twenty-four-year longitudinal study. SETTING: Southern California community.
      PARTICIPANTS: One thousand seventy-six members of the Rancho Bernardo cohort aged
      50 to 89 at baseline. MEASUREMENTS: Participants completed two to six research
      visits at approximately 4-year intervals between 1984 and 2009. At each visit,
      participants completed standard questionnaires on alcohol use, chronic diseases,
      and behaviors. Mixed-effects linear models were used to examine changes in
      average weekly alcohol intake over time and in relationship to health status.
      RESULTS: Prevalence and frequency of alcohol use was high throughout the study,
      with more than 60% of participants reporting weekly alcohol intake. The average
      amount consumed declined with advancing age, regardless of the presence of any of
      the eight most common chronic diseases. Prevalence of drinking in excess of age-
      and sex-specific low-risk guidelines was high across all visits and did not vary
      according to disease burden. At the final visit, 29% of participants drank in
      excess of low-risk drinking guidelines, including 28% of those with hypertension
      and 31% with diabetes mellitus. CONCLUSION: Prevalence and frequency of alcohol
      intake remained stable over a 24 year follow-up in this cohort of educated,
      white, middle-class, older adults, although average amount consumed decreased
      with advancing age. Despite this decrease, a high proportion of older adults,
      including those with common chronic health conditions, drank in excess of current
      guidelines. Clinicians should provide more education on the importance of older
      adults moderating alcohol intake.

PMID- 23865907
TI  - The impact of falls prevention on participation in daily occupations of older
      adults following discharge: a systematic review and meta-analysis.
AB  - PURPOSE: To investigate the impact of falls intervention programmes on
      participation of older adults returning home to live, following discharge from
      hospital. METHOD: A systematic review of peer-reviewed articles and grey
      literature was completed. Limits were set for articles published in English,
      dated 1990-2012. Inclusion criteria included randomised control trials with older
      adults (>=65 years) that used an effective falls intervention and a participation
      measure, following discharge from hospital or emergency department. Two
      independent researchers assessed the studies for eligibility. Research risk of
      bias was evaluated using the PEDro scale (range 1-10). A meta-analysis of the
      selected articles was completed. RESULTS: Five studies fulfilled the inclusion
      criteria and measured participation outcomes short-term (<six months post
      discharge, n = 488) and long-term (6-12 months post-discharge, n = 571). The
      results indicated that falls interventions provided a positive improvement in
      patients' participation level (p = 0.042, p = 0.026). However, the effect size
      was small at 0.20 and 0.21. CONCLUSIONS: The meta-analysis findings indicate that
      there is a causal association between falls interventions and participation in
      daily occupations with older adults post-discharge. Although the effect size was
      small, practice implications of this study suggest that participation needs to be
      considered in future falls prevention research. Implications for Rehabilitation
      Falls interventions for older adults following discharge home from hospital,
      increase participation in life situations to a small extent. Health professionals
      can include a focus on falls prevention programmes with older adults to promote
      participation.

PMID- 23865908
TI  - Physical activity and low back pain: the role of subgroups based on the avoidance
      endurance model.
AB  - PURPOSE: This study examines the relationship between low back pain, disability
      and fatigue and overt physical activity with respect to fear-avoidance and
      endurance-related subgroups. METHOD: 49 patients completed questionnaires (Pain,
      Disability, Fatigue, Depression, Pain-responses pattern) 6 months after lumbar
      disc surgery and underwent an 8-hour accelerometer assessment measuring overall
      physical activity (PAL), constant strain postures (CSP), standing time (ST) and
      lying time (LT). Four subgroups, representing patterns of distress-endurance
      (DER), eustress-endurance (EER), fear-avoidance (FAR) and adaptive responses (AR)
      due to the avoidance-endurance model of pain-regulation were investigated.
      RESULTS: Multivariate analyses of covariance revealed significantly higher pain,
      disability and fatigue in FAR compared to AR patients and, as expected lower PAL
      and CSP in FAR than in endurance patients. Both endurance groups revealed higher
      pain accompanied by higher accelerometer-based physical activity (PAL, CSP) than
      AR and FAR patients. Most of the subgroup differences displayed moderate to high
      effect sizes. CONCLUSIONS: The results indicate different pathways to chronic
      pain and disability with physical underuse in FAR patients and overuse/overload
      in endurance patients suggesting the need for individually targeted cognitive
      behavioral treatments in the maladaptive groups. Implications for Rehabilitation
      Improving the return to a normal physical activity level is an important goal for
      the rehabilitation of patients after lumbar disc surgery. Different pathways to
      chronic pain and disability with physical underuse in fear-avoidance patients and
      overuse in endurance patients should be considered. Different pain-related pain
      response pattern, based on the avoidance-endurance model, indicate the need for
      individual targeting of rehabilitation programs.

PMID- 23865909
TI  - What place for ethics? An overview of ethics teaching in occupational therapy and
      physiotherapy programs in Canada.
AB  - PURPOSE: The recent introduction of master's level curricula for Occupational
      Therapy (OT) and Physiotherapy (PT) training programs in Canada raises both
      challenges and opportunities to address ethical issues during professional
      training. This study evaluated the inclusion of ethics content in course
      descriptions and course calendars in order to develop a preliminary understanding
      of how rehabilitation ethics is taught in Canadian universities. METHOD: We
      reviewed the ethics content in the online curricula of 27 Canadian rehabilitation
      programs (OT & PT). Courses addressing ethical issues were identified through
      keyword searches, and were then subjected to both quantitative and textual
      descriptive analyses. RESULTS: The mean proportion of credits allotted to courses
      that included ethics terminology was 5.9% (SD = 1.4) for OT and 6.5% (SD = 4.8)
      for PT (p = 0.69). The most common terms in the course descriptions were
      "ethics/ethical" followed by "legal", "professionalism", "deontology" and
      "regulatory". Textual analysis revealed eight course topics, the most frequent
      being: standards of practice, ethical decision-making, clinical courses and
      mediation/communication. CONCLUSION: With the growing recognition and status of
      OT and PT in the healthcare system, and corresponding shifts in how professionals
      are being trained, it is crucial to assess and reflect upon the place accorded to
      and manner of teaching ethics. Implications for Rehabilitation Ethics training in
      rehabilitation programs With the evolving recognition of OT and PT professions
      within the healthcare system, and corresponding shifts in how future
      professionals are trained, it is crucial to assess the place accorded to teaching
      ethics. In Canadian OT and PT programs, ethics content is most commonly included
      in broad courses related to standards of practice and not in specific ethics
      courses. Careful attention is needed to ensure that OT and PT students receive
      sufficient ethics training that is well aligned with their future practice
      context to support them to competently address the ethical issues that they will
      encounter in clinical practice. In addition, OT and PT professionals would
      benefit from the development of continuing education activities that target
      ethical issues relevant to their practice.

PMID- 23865913
TI  - The value of clinical electrophysiology in the assessment of the eye and visual
      system in the era of advanced imaging.
AB  - Electrophysiological techniques allow clinical investigations to include a
      'dissection' of the visual system. Using suitable electrophysiological
      techniques, the 'dissection' allows function to be ascribed to the different
      photoreceptors (rod and cone photoreceptors), retinal layers, retinal location or
      the visual pathway up to the visual cortex. Combined with advances in genetics,
      retinal biochemistry, visual fields and ocular imaging, it is now possible to
      obtain a better understanding of diseases affecting the retina and visual
      pathways. This paper reviews core electrophysiological principles that can
      complement other examination techniques, including advanced ocular imaging, and
      help the interpretation of other clinical data and thus, refine and guide
      clinical diagnosis. 

PMID- 23865912
TI  - Conservation of the genes for HC-toxin biosynthesis in Alternaria jesenskae.
AB  - BACKGROUND: HC-toxin, a cyclic tetrapeptide, is a virulence determinant for the
      plant pathogenic fungus Cochliobolus carbonum. It was recently discovered that
      another fungus, Alternaria jesenskae, also produces HC-toxin. RESULTS: The major
      genes (collectively known as AjTOX2) involved in the biosynthesis of HC-toxin
      were identified from A. jesenskae by genomic sequencing. The encoded orthologous
      proteins share 75-85% amino acid identity, and the genes for HC-toxin
      biosynthesis are duplicated in both fungi. The genomic organization of the genes
      in the two fungi show a similar but not identical partial clustering arrangement.
      A set of representative housekeeping proteins show a similar high level of amino
      acid identity between C. carbonum and A. jesenskae, which is consistent with the
      close relatedness of these two genera within the family Pleosporaceae
      (Dothideomycetes). CONCLUSIONS: This is the first report that the plant virulence
      factor HC-toxin is made by an organism other than C. carbonum. The genes may have
      moved by horizontal transfer between the two species, but it cannot be excluded
      that they were present in a common ancestor and lost from other species of
      Alternaria and Cochliobolus.

PMID- 23865914
TI  - Whole-exome sequencing identifies MYO15A mutations as a cause of autosomal
      recessive nonsyndromic hearing loss in Korean families.
AB  - BACKGROUND: The genetic heterogeneity of hearing loss makes genetic diagnosis
      expensive and time consuming using available methods. Whole-exome sequencing has
      recently been introduced as an alternative approach to identifying causative
      mutations in Mendelian disorders. METHODS: To identify the hidden mutations that
      cause autosomal recessive nonsyndromic hearing loss (ARNSHL), we performed whole
      exome sequencing of 13 unrelated Korean small families with ARNSHL who were
      negative for GJB2 or SLC26A4 mutations. RESULTS: We found two novel compound
      heterozygous mutations, IVS11 + 1 and p.R2146Q, of MYO15A in one (SR903 family)
      of the 13 families with ARNSHL. In addition to these causative mutations, 13
      nonsynonymous variants, including variants with uncertain pathogenicity (SR285
      family), were identified in the coding exons of MYO15A from Korean exomes.
      CONCLUSION: This is the first report of MYO15A mutations in an East Asian
      population. We suggest that close attention should be paid to this gene when
      performing genetic testing of patients with hearing loss in East Asia. The
      present results also indicate that whole-exome sequencing is a valuable method
      for comprehensive medical diagnosis of a genetically heterogeneous recessive
      disease, especially in small-sized families.

PMID- 23865915
TI  - Migraine relief by chilis and other alternative medications: evidence indicates a
      central role for trp channels.

PMID- 23865916
TI  - Fatigue is increased in episodic migraine without aura patients.

PMID- 23865917
TI  - Botulinum toxin-A is an effective and safe treatment for chronic migraine.

PMID- 23865918
TI  - Nummular headache related to exercise or Valsalva maneuver. Clinical
      characteristics of 3 cases.

PMID- 23865919
TI  - Headache after sports-related concussion.

PMID- 23865921
TI  - Clinical significance of aberrant vimentin expression in oral premalignant
      lesions and carcinomas.
AB  - OBJECTIVE: To investigate the clinical significance of vimentin expression at
      early and late events of tobacco/areca nut-associated oral tumorigenesis.
      MATERIALS AND METHODS: Immunohistochemistry (IHC) was carried out on paraffin
      embedded tissues of oral mucosa normal (n = 10), inflammatory lesions (n = 19),
      leukoplakia (n = 52), submucous fibrosis (n = 71) and tumours/cut margins (n =
      227 each), using anti-vimentin antibody, and the expression profile was
      correlated with patients' clinical parameters. Immunofluorescence, Western blot
      and RT-PCR analysis were also carried out wherever adequate and fresh tissues
      were available. RESULTS: Aberrant vimentin expression was seen in hyperplastic,
      dysplastic and fibrotic tissues, which showed statistically significant
      correlation with the histopathological grade of dysplasia (P = 0.001) and
      fibrosis (P = 0.009). Vimentin expression also showed statistically significant
      correlation with tumour size (P = 0.048), clinical stage (P = 0.013), regional
      lymph node metastases (P = 0.001), local recurrence (P = 0.001) and survival (P =
      0.021) of patients with oral squamous cell carcinoma (OSCC). Its expression in
      invasive fronts statistically correlated with development of nodal metastasis and
      local recurrence. CONCLUSIONS: Our results suggest possible role of vimentin in
      early events of tobacco/areca nut-associated oral tumorigenesis, which may prove
      useful to predict the malignant potential of high-risk oral lesions. Further,
      association between vimentin expression in invasive fronts and aggressive
      phenotype of tumours may help clinicians to choose the appropriate treatment
      modality for OSCC management.

PMID- 23865922
TI  - Sugar-sweetened beverages.

PMID- 23865923
TI  - Nursing leadership and patient outcomes.

PMID- 23865924
TI  - The relationship between nursing leadership and patient outcomes: a systematic
      review update.
AB  - AIM: Our aim was to describe the findings of a systematic review of studies that
      examine the relationship between nursing leadership practices and patient
      outcomes. BACKGROUND: As healthcare faces an economic downturn, stressful work
      environments, upcoming retirements of leaders and projected workforce shortages,
      implementing strategies to ensure effective leadership and optimal patient
      outcomes are paramount. However, a gap still exists in what is known about the
      association between nursing leadership and patient outcomes. METHODS: Published
      English-only research articles that examined leadership practices of nurses in
      formal leadership positions and patient outcomes were selected from eight online
      bibliographic databases. Quality assessments, data extraction and analysis were
      completed on all included studies. RESULTS: A total of 20 studies satisfied our
      inclusion criteria and were retained. Current evidence suggests relationships
      between positive relational leadership styles and higher patient satisfaction and
      lower patient mortality, medication errors, restraint use and hospital-acquired
      infections. CONCLUSIONS: The findings document evidence of a positive
      relationship between relational leadership and a variety of patient outcomes,
      although future testing of leadership models that examine the mechanisms of
      influence on outcomes is warranted. IMPLICATIONS FOR NURSING MANAGEMENT: Efforts
      by organisations and individuals to develop transformational and relational
      leadership reinforces organisational strategies to improve patient outcomes.

PMID- 23865925
TI  - The effect of nurse manager turnover on patient fall and pressure ulcer rates.
AB  - AIMS: The purpose of this study was to explore the effects of nurse manager
      turnover on the occurrence of adverse events. BACKGROUND: Nurse managers create
      professional nurse practice environments to support the provision of quality
      patient outcomes. Inconsistent findings were reported in the literature testing
      the relationship between nurse managers and patient outcomes. All prior studies
      assumed stable nursing management. METHODS: A longitudinal quasi-experimental
      study of 23 nursing units in two hospitals was used to determine whether unit
      characteristics, including nurse manager turnover, have an effect on patient
      falls or pressure ulcers. Statistical analyses included repeated measures and
      hierarchical modelling. RESULTS: Patients in medical/surgical units experienced
      more falls than in intensive care units (F1,11 = 15.9, P = 0.002). Patients in
      units with a nurse manager turnover [odds ratio: 3.16; 95% confidence interval:
      1.49-6.70] and intensive care units (odds ratio: 2.70; 95% confidence interval:
      1.33-5.49) were more likely to develop pressure ulcers. CONCLUSIONS: Nurse
      manager turnover and intensive care unit status were associated with more
      pressure ulcers. Medical/surgical unit status was associated with more falls. The
      study was limited by a small sample size. IMPLICATIONS FOR NURSE MANAGERS: Nurse
      manager turnover may negatively impact patient outcomes. Stable nursing
      management, strategic interim management and long-term succession planning may
      reduce adverse patient events.

PMID- 23865926
TI  - Discharge phone calls: using person-centred communication to improve outcomes.
AB  - AIM: This article describes the Clinical Nurse Leader role in implementing person
      centred care bundles to improve patient outcomes through an innovative culture of
      caring. BACKGROUND: Demonstrating the financial value of introducing the Clinical
      Nurse Leader role into an organisation is essential for sustainability. Previous
      authors have established the Clinical Nurse Leaders' influence on patient
      satisfaction and have suggested that Clinical Nurse Leaders improve the
      continuity of care after discharge. EVALUATION: Descriptive data are shared to
      illustrate the effectiveness of implementing the patient care bundles and a
      Clinical Nurse Leader-driven discharge phone call process. KEY ISSUES: Clinical
      Nurse Leaders who practise from a caring lens are uniquely situated to lead
      initiatives that drive person-centred care with the goal of reducing readmission
      rates. Patients who receive person-centred care have an improved perception of
      the hospital experience and are more likely to return to the facility.
      CONCLUSIONS: Clinical Nurse Leaders establish relationships with patients that
      increase the likelihood of successful outcomes from the discharge phone call
      process. Further evaluation of the Clinical Nurse Leader's role and potential
      impact on patient outcomes is warranted. IMPLICATIONS FOR NURSING MANAGEMENT:
      Clinical Nurse Leaders are uniquely prepared to lead transformational change
      within an organisation. Clinical Nurse Leader interventions that are developed at
      the microsystem level in response to problems may have system-wide implications.

PMID- 23865927
TI  - Authentic leadership and nurse-assessed adverse patient outcomes.
AB  - AIM: Our purpose was to test a model examining relationships among authentic
      leadership, nurses' trust in their manager, areas of work life and nurse-assessed
      adverse patient outcomes. BACKGROUND: Although several work environment factors
      have been cited as critical to patient outcomes, studies linking nursing
      leadership styles with patient outcomes are limited suggesting the need for
      additional research to investigate the mechanisms by which leadership may
      influence patient outcomes. METHODS: Secondary analysis of data collected in a
      cross-sectional survey of 280 (48% response rate) registered nurses working in
      acute care hospitals in Ontario was conducted using structural equation
      modelling. RESULTS: The final model fit the data acceptably (chi(2) = 1.30, df =
      2, P = 0.52, IFI = 0.99, CFI = 1.00, RMSEA = 0.00). Authentic leadership was
      significantly associated with decreased adverse patient outcomes through trust in
      the manager and areas of work life. CONCLUSIONS: The findings suggest that nurses
      who see their managers as demonstrating high levels of authentic leadership
      report increased trust, greater congruence in the areas of work life and lower
      frequencies of adverse patient outcomes. IMPLICATIONS FOR NURSING MANAGEMENT:
      Managers who emphasize transparency, balanced processing, self-awareness and high
      ethical standards in their interactions with nurses may contribute to safer work
      environments for patients and nurses.

PMID- 23865928
TI  - Multi-level barriers analysis to promote guideline based nursing care: a
      leadership strategy from home health care.
AB  - BACKGROUND: Understanding the types of barriers that exist when implementing
      change can assist healthcare managers to tailor implementation strategies for
      optimal patient outcomes. AIM: The aim of this paper is to present an organising
      framework, the Barriers Assessment Taxonomy, for understanding barriers to
      nurses' use of clinical practice guideline recommendations. Barriers to
      recommendations are illustrated using the Barriers Assessment Taxonomy and
      insights discussed. METHOD: As part of a pilot implementation study, semi
      structured interviews (n = 26) were conducted to understand barriers to nurses'
      use of nine guideline recommendations for diabetic foot ulcers. Content analysis
      of verbatim transcripts included thematic coding and categorising barriers using
      the Barriers Assessment Taxonomy. RESULTS: Nineteen barriers were associated with
      nine recommendations, crossing five levels of the health care delivery system.
      The Barriers Assessment Taxonomy revealed that all recommendations had individual
      and organisational level barriers, with one recommendation having barriers at all
      levels. Individual level barriers were most frequent and lack of knowledge and
      skills was the only barrier that crossed all recommendations. IMPLICATIONS FOR
      NURSING MANAGEMENT: The Barriers Assessment Taxonomy provides a framework for
      nursing managers to understand the complexity of barriers that exist, and can
      assist in choosing intervention strategies to support improved quality care and
      patient outcomes.

PMID- 23865929
TI  - Determinants of regulated nurses' intention to stay in long-term care homes.
AB  - AIM: To examine determinants of intent to stay among regulated nurses employed in
      long-term care facilities. BACKGROUND: Elderly persons living in long-term care
      have increasingly complex care needs, putting greater demands on health-care
      providers. Indeed, regulated nursing staff employed in long-term care facilities
      represent the largest group of health-care providers who intend to leave their
      current jobs. METHODS: Survey responses from 155 nurses from 12 long-term care
      facilities were analyzed to test the impact of six predictors on intent to stay.
      RESULTS: Intention to stay was positively associated with lower burnout, higher
      job satisfaction, older nurses and resident relationships. Work relationships
      were negatively associated with intention to stay. Leadership support was not a
      significant predictor. CONCLUSION: Most predictors were correlated with intention
      to stay as hypothesized. Further research is warranted to investigate the
      influence of management practices and work relationships on regulated nursing
      staff's intent to stay in long-term care. IMPLICATIONS FOR NURSING MANAGEMENT: To
      retain qualified nursing staff and ensure quality of care, long-term care
      administrators should focus on creating a work environment that reduces burnout,
      increases job satisfaction, and enables nurses to foster relationships with
      residents. Recommendations for long-term care administrators include: (1) provide
      opportunities for self-scheduling, full-time work and benefits; (2) develop
      models of care that enhance resident relationships; (3) examine existing
      regulated nursing staff responsibilities and adjust to minimize burnout.

PMID- 23865930
TI  - How can a social capital framework guide managers to develop positive nurse
      relationships and patient outcomes?
AB  - AIM: To examine how social capital could be a mediating factor through which
      managers' leadership positively influences relationships with nurses and quality
      patient outcomes. BACKGROUND: The relationship between leadership, what managers
      do and optimal outcomes for patients are well established. What is not yet clear
      is an understanding about specific mechanisms by which managers' leadership
      builds social capital to foster cohesive team relationships and quality patient
      outcomes. KEY ISSUES: Conceptual links are drawn between human capital and
      leadership styles of managers. Social capital is introduced and contextualized
      through exemplars from a Canadian study. Exemplars illustrate how the presence or
      absence of social capital influenced nurses' productivity to deliver quality
      patient care. CONCLUSIONS: Nurse researchers could use the Social Capital
      Framework (SCF) to examine the mediating role of social capital in relationships
      between managers and nurses. These findings could inform managers' strategies to
      foster positive networks and norms between nurses to deliver quality patient
      care. IMPLICATIONS FOR NURSING MANAGEMENT: Leadership that uses a framework of
      social capital will enhance team relationships between nurses. Enhanced cohesion
      will have a positive impact on patient outcomes.

PMID- 23865931
TI  - Using a social capital framework to enhance measurement of the nursing work
      environment.
AB  - AIM: To develop, field test and analyse a social capital survey instrument for
      measuring the nursing work environment. BACKGROUND: The concept of social
      capital, which focuses on improving productive capacity by examining
      relationships and networks, may provide a promising framework to measure and
      evaluate the nurse work environment in a variety of settings. METHODS: A survey
      instrument for measuring social capital in the nurse work environment was
      developed by adapting the World Bank's Social Capital - Integrated Questionnaire
      (SC-IQ). Exploratory factor analysis and multiple regression analyses were
      applied to assess the properties of the instrument. RESULTS: The exploratory
      factor analysis yielded five factors that align well with the social capital
      framework, while reflecting unique aspects of the nurse work environment.
      CONCLUSION: The results suggest that the social capital framework provides a
      promising context to assess the nurse work environment. Further work is needed to
      refine the instrument for a diverse range of health-care providers and to
      correlate social capital measures with quality of patient care. IMPLICATIONS FOR
      NURSING MANAGEMENT: Social capital measurement of the nurse work environment has
      the potential to provide managers with an enhanced set of tools for building
      productive capacity in health-care organisations and achieving desired outcomes.

PMID- 23865933
TI  - Chiral phosphoric acid-catalyzed oxidative kinetic resolution of indolines based
      on transfer hydrogenation to imines.
AB  - The oxidative kinetic resolution of 2-substituted indoline derivatives was
      achieved by hydrogen transfer to imines by means of a chiral phosphoric acid
      catalyst. The oxidative kinetic resolution was applicable to racemic alkyl- or
      aryl-substituted indolines, and the remaining indolines were obtained in good
      yields with excellent enantioselectivities. 

PMID- 23865932
TI  - Evolutionary dynamics of retrotransposable elements Rex1, Rex3 and Rex6 in
      neotropical cichlid genomes.
AB  - BACKGROUND: Transposable elements (TEs) have the potential to produce broad
      changes in the genomes of their hosts, acting as a type of evolutionary toolbox
      and generating a collection of new regulatory and coding sequences. Several TE
      classes have been studied in Neotropical cichlids; however, the information
      gained from these studies is restricted to the physical chromosome mapping,
      whereas the genetic diversity of the TEs remains unknown. Therefore, the genomic
      organization of the non-LTR retrotransposons Rex1, Rex3, and Rex6 in five
      Amazonian cichlid species was evaluated using physical chromosome mapping and DNA
      sequencing to provide information about the role of TEs in the evolution of
      cichlid genomes. RESULTS: Physical mapping revealed abundant TE clusters
      dispersed throughout the chromosomes. Furthermore, several species showed
      conspicuous clusters accumulation in the centromeric and terminal portions of the
      chromosomes. These TE chromosomal sites are associated with both heterochromatic
      and euchromatic regions. A higher number of Rex1 clusters were observed among the
      derived species. The Rex1 and Rex3 nucleotide sequences were more conserved in
      the basal species than in the derived species; however, this pattern was not
      observed in Rex6. In addition, it was possible to observe conserved blocks
      corresponding to the reverse transcriptase fragment of the Rex1 and Rex3 clones
      and to the endonuclease of Rex6. CONCLUSION: Our data showed no congruence
      between the Bayesian trees generated for Rex1, Rex3 and Rex6 of cichlid species
      and phylogenetic hypothesis described for the group. Rex1 and Rex3 nucleotide
      sequences were more conserved in the basal species whereas Rex6 exhibited high
      substitution rates in both basal and derived species. The distribution of Rex
      elements in cichlid genomes suggests that such elements are under the action of
      evolutionary mechanisms that lead to their accumulation in particular chromosome
      regions, mostly in heterochromatins.

PMID- 23865934
TI  - trans-[Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] incorporated in PLGA
      nanoparticles for the delivery of nitric oxide to B16-F10 cells: cytotoxicity and
      phototoxicity.
AB  - The immobilization and characterization of trans-[Ru(NO)Cl(cyclam)](PF6)2
      (cyclam=1,4,8,11-tetraazacyclotetradecane), and [Ru(NO)(Hedta)]
      (Hedta=ethylenediaminetetraacetic acid) entrapped in poly(d,l-lactic-co-glycolic)
      acid (PLGA) nanoparticles (NP) using the double emulsification process is
      described. Scanning electron microscopy and dynamic light scattering revealed
      that the particles are spherical in shape, have a size distribution between 220
      and 840 nm of diameter, and have a tendency to aggregate confirmed by a zeta
      potential between -3.2 and +3.5 mV. Using this method the loading efficiency was
      26% for trans-[Ru(NO)Cl(cyclam)](PF6)2 and 32% for [Ru(NO)(Hedta)]. The release
      of the complexes from the NPs shows that cyclam-NP and Hedta-NP exhibited a two
      phase exponential association release pattern, which was characterized by an
      initial complex burst during the first 24 h, followed by a slower release phase
      complex profile, due to a few pores observed in surface of nanoparticles using
      atomic force microscopy. The in vitro cytotoxic activity of the nitrosyl
      complexes in solution and incorporated in PLGA nanoparticles on melanoma cancer
      cells (cell line B16-F10) was investigated. The lower cytotoxicity of trans
      [RuCl(cyclam)(NO)]2+ (12.4+/-2.6%) and [Ru(NO)(Hedta)] (4.0+/-2.7%) in solution
      compared to that of trans-[Ru(NO)(NH3)4py]3+ (46.1+/-6.4%) is consistent with the
      rate constant release of NO of these complexes (k-NO=6.2*10(-4) s(-1), 2.0*10(-3)
      s(-1), and 6.0*10(-2) s(-1), respectively); the cytotoxicities are also inhibited
      in the presence of the NO scavenger carboxy-PTIO. The phototoxicity of these
      complexes is due to NO release, which lead to 53.8+/-6.2% of cell death in the
      presence of trans-[Ru(NO)Cl(cyclam)](PF6)2 and 22.3+/-5.1% in the presence of
      [Ru(NO)(Hedta)]. The PLGA nanoparticles loaded with trans
      [Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] exerted in vitro a reduced activity
      against melanoma cells when compared to the activity of complex in solution
      (nonentrapped in nanoparticles). Blank PLGA nanoparticles did not exhibit
      cytotoxicity. In the presence of light and of ruthenium nitrosyl complexes or
      cyclam-NP and Hedta-NP, B16-F10 cells displayed a considerable damage of the
      surface with rupture of the plasma membrane. This behavior is an indicative of
      the efficiency of the DDS to deliver the NO from the entrapped complex when
      photoinduced.

PMID- 23865935
TI  - Photobacterium damselae in bigeye scad, Selar crumenophthalmus (Bloch), from
      Grenada, West Indies.

PMID- 23865936
TI  - Landscape framework and global stability for stochastic reaction diffusion and
      general spatially extended systems with intrinsic fluctuations.
AB  - Spatially extended systems are widely encountered in physics, chemistry, and
      biology for studying many important natural phenomena. In this work, we
      established a landscape framework for studying general stochastic spatially
      extended systems with intrinsic statistical fluctuations that can be applied to
      both equilibrium systems with detailed balance and nonequilibrium systems without
      detailed balance. We set up the master equation for general stochastic spatially
      extended systems (functional master equation) from two fundamental dynamical
      ingredients that characterize the elementary state transitions of spatially
      extended systems. We explored the entire spectrum of the various approximations
      of the functional master equation under certain conditions, from the functional
      Kramers-Moyal equation to the functional Fokker-Planck equation and its
      equivalent, the functional Langevin equation, to the macroscopic deterministic
      equation. We uncovered the Lyapunov functionals which are required to quantify
      the global stability and function of the system for both the deterministic and
      stochastic spatially extended systems. The global potential landscape functional
      for stochastic spatially extended systems can be quantified by the steady state
      probability distribution functional. In the small fluctuation limit, the
      potential landscape functional becomes the Lyapunov functional for the
      corresponding deterministic spatially extended system. The relative entropy
      functional (or free energy functional) proves to be the Lyapunov functional for
      the stochastic spatially extended systems. The potential landscape functional and
      the relative entropy functional quantify the global stability and function of the
      deterministic and stochastic spatially extended systems for both equilibrium and
      nonequilibrium conditions. The chemical reaction-diffusion systems as a typical
      and important class of spatially extended systems is explored on its own terms as
      well as used as a direct application of the general framework to derive more
      specific results for reaction-diffusion systems. A biological system, the bicoid
      protein concentration distribution in fruit fly embryo development, which can be
      modeled as a specific type of reaction-diffusion dynamics, is studied using the
      proposed framework. We found both the bicoid concentration and its fluctuation
      decay from anterior to posterior when the source producing the bicoid protein is
      located at the anterior point. The corresponding local funneled landscape basin
      of the bicoid concentration becomes narrower and steeper from anterior to
      posterior in such a case. 

PMID- 23865937
TI  - Cortisol secretion from adrenal adenomas discovered as incidentalomas is
      responsive to ACTH.
AB  - OBJECTIVE: Adrenal adenomas discovered as incidentalomas may secrete cortisol and
      cause subclinical hypercortisolism. This cortisol secretion is considered to be
      autonomous. The aim was to investigate whether cortisol secretion by adenomas is
      responsive to ACTH. DESIGN: Descriptive retrospective study of consecutive
      patients. PATIENTS: Eighty patients found to have adrenal incidentalomas during
      2008 and 2009 at our hospital were examined, and 50 patients with a unilateral
      adenoma were included in the study. MEASUREMENTS: Cortisol and ACTH were measured
      at baseline and using 1-mg overnight dexamethasone suppression test (DST). The
      cortisol response to ACTH was calculated using the expression: (cortisolbasal 
      cortisolDST )/(ACTHbasal -ACTHDST ). RESULTS: The patients were divided into
      three groups according to their basal ACTH: >=3.0 pm (29 patients), 2.0-2.9 pm (9
      patients) and <2.0 pm (12 patients). Cortisol at DST was similar in the three
      groups: 30, 46 and 43 nm (P = 0.10). The cortisol response to ACTH increased
      stepwise between the groups: 98, 172 and 249 nm/pm (P = 0.000, undetectable ACTH
      was set to 0 pm). Basal ACTH was negatively correlated with the size of the
      adenoma and positively correlated with the attenuation of the adenoma at
      unenhanced CT (P = 0.03 and P = 0.04, respectively). CONCLUSIONS: Patients with
      adrenal adenomas and low basal ACTH show increased cortisol response to ACTH, and
      the adenomas seem to be the source of the increased cortisol secretion. The
      increased response to ACTH could be a pathogenic factor in metabolic
      complications of subclinical hypercortisolism. The cortisol response to ACTH may
      therefore be a useful measure of subclinical hypercortisolism.

PMID- 23865938
TI  - Analysis of single-case data: randomisation tests for measures of effect size.
AB  - Single-case experiments can be used to evaluate the effect of an intervention or
      treatment for a single entity. The internal validity and statistical conclusion
      validity of single-case experiments can be improved by incorporating
      randomisation in their design. In this article, we explain how to design
      randomised single-case phase and alternation studies as well as randomised
      simultaneous and sequential replication studies, and how to conduct randomisation
      tests for these designs. Advantages and limitations of randomisation tests are
      discussed. In order to not only determine the (non)randomness of an intervention
      effect, but also the magnitude of this effect, we propose to use an effect size
      index as a test statistic for the randomisation test. We illustrate this
      combination for the design and analysis of an ABAB phase study, using a free
      software package. 

PMID- 23865939
TI  - Rational design, synthesis, and characterization of deep blue phosphorescent
      Ir(III) complexes containing (4'-substituted-2'-pyridyl)-1,2,4-triazole ancillary
      ligands.
AB  - On the basis of the results of frontier orbital considerations, 4-substituted-2'
      pyridyltriazoles were designed to serve as ancillary ligands in 2-phenylpyridine
      main ligand containing heteroleptic iridium(III) complexes that display deep blue
      phosphorescence emission. The iridium(III) complexes, Ir1-Ir7, prepared using the
      new ancillary ligands, were found to display structured, highly quantum efficient
      (Phip = 0.20-0.42) phosphorescence with emission maxima in the blue to deep blue
      448-456 nm at room temperature. In accord with predictions based on frontier
      orbital considerations, the complexes were observed to have emission properties
      that are dependent on the electronic nature of substituents at the C-4 position
      of the pyridine moiety of the ancillary ligand. Importantly, placement of an
      electron-donating methyl group at C-4' of the pyridine ring of the 5-(pyridine-2'
      yl)-3-trifluoromethyl-1,2,4-triazole ancillary ligand leads to an iridium(III)
      complex that displays a deep blue phosphorescence emission maximum at 448 nm in
      both the liquid and film states at room temperature. Finally, an OLED device,
      constructed using an Ir-complex containing the optimized ancillary ligand as the
      dopant, was found to emit deep blue color with a CIE of 0.15, 0.18, which is
      close to the perfect goal of 0.15, 0.15. 

PMID- 23865940
TI  - A simple computer-assisted quantification of contrast in a fingerprint.
AB  - A simple method for quantification of contrast in a fingerprint is proposed.
      Contrast is defined as the average difference in intensity of pixels between
      valleys and ridges in a fingerprint. It is quantified from a scanner-acquired
      image of the fingerprint using a histogram function of Adobe Photoshop. The
      method was validated with black inked prints and marks developed with aluminum
      powder. Moreover, we tested resistance of the method to rater-dependent errors
      and dependence of the measurements on the resolution of an image and the model of
      the scanner. For both groups of fingerprints, the method gave coherent and easily
      interpretable quantitative values for contrast. There were no significant
      differences between measurements performed by different raters and by the same
      rater in a test-retest procedure. However, the method was found to be instrument
      dependent, as measurements were significantly affected by image resolution and
      the model of the scanner. 

PMID- 23865941
TI  - Abstracts of the 8th World Congress of Melanoma, the 9th Congress of the European
      Association of Dermatology (EADO), the 7th Interdisciplinary Melanoma/Skin Cancer
      Meeting, and the 3rd European Post-Chicago Melanoma Meeting. July 17-20, 2013.
      Hamburg, Germany.

PMID- 23865944
TI  - A novel approach to efficient access of dermatologic device settings and
      maintenance records using retractable information sheets.

PMID- 23865943
TI  - Humoral and cell-mediated immune responses to different doses of attenuated
      vaccine against avian infectious bronchitis virus.
AB  - The antibody and cellular immune responses against infectious bronchitis virus
      (IBV) were evaluated at mucosal sites of chickens after immunization with various
      doses of an attenuated vaccine at 1 day of age. The correlation of these immune
      responses with protection of tracheal tissues was evaluated after experimental
      infection of these birds. Significantly reduced tracheal pathologic effects,
      measured according to ciliostasis and histology lesions, and reduced viral load
      were observed only in the full-dose vaccinated group at 5 days post-infection
      (dpi), while incomplete protection was observed for the subdose vaccinated
      groups. Moreover, birds of vaccinated groups, especially with full dose,
      developed higher levels of lachrymal IBV-specific IgG and IgA and increased the
      expression of cell-mediated immunity (CMI) genes, such as gamma interferon
      (IFNgamma), CD8+ T cell marker, and granzyme homolog A more rapidly. In addition,
      these humoral and cellular immune responses evaluated at mucosal sites correlated
      significantly with tracheal protection against homologous IBV challenge in a
      vaccine dose-dependent manner. The results indicate that IgG, IgA and CD8+ T cell
      responses developed at mucosal sites after IBV vaccination of day-old chicks,
      could be taken as good correlates of protection against this virus.

PMID- 23865945
TI  - Predictive approaches to increase absorption of compounds during lead
      optimisation.
AB  - INTRODUCTION: Complex physicochemical and biological processes influence the oral
      absorption of a drug molecule. Consideration of these processes is an important
      activity during the optimisation of potential candidate molecules. AREAS COVERED:
      The authors review the applications of physicochemical and structural
      requirements for intestinal absorption. Furthermore, they provide examples of how
      to aid the lead optimisation process through improvement of solubility and
      permeability. EXPERT OPINION: The physicochemical requirements for absorption are
      solubility and permeability. Both are influenced by lipophilicity, but in the
      opposite way. The size of the molecule also affects both solubility and
      permeability. Several models can be used to estimate oral absorption from
      chemical structure or from measured physicochemical properties. Thus, logD-cMR
      model, the 'golden triangle' model, Abraham solvation equations and absorption
      potential can be used as tools in the lead optimisation process. Measured values
      of solubility and permeability greatly improve the estimation of in vivo oral
      absorption of compounds. However, it is important to appreciate that predictions
      of oral absorption may be confounded by the involvement of active transporters in
      the gut which may either increase (e.g., active uptake) or decrease (e.g.,
      efflux) the absorption of drug molecules. To evaluate the first-pass metabolism,
      in vitro clearance measurements using liver microsomes can be used in
      physiologically based models for the estimation of bioavailability. The general
      tools discussed in this review are based on the physicochemical property
      assessment of compound libraries and they help design compounds that occupy
      desirable property space with increased likelihood of good oral absorption.

PMID- 23865946
TI  - Effect of a ctrA promoter mutation, causing a reduction in CtrA abundance, on the
      cell cycle and development of Caulobacter crescentus.
AB  - BACKGROUND: Polar development during the alphaproteobacterium Caulobacter
      crescentus cell cycle is integrated to the point that individual mutations can
      have pleiotropic effects on the synthesis of polar organelles. Disruption of the
      genes encoding the histidine kinase PleC, or its localization factor PodJ,
      disrupts synthesis or functionality of pili, flagella and adhesive holdfast.
      However, the mechanism by which these mutations affect polar development is not
      well understood. The aim of this study was to identify new regulators that
      control multiple aspects of polar organelle development. RESULTS: To identify
      mutants with pleiotropic polar organelle synthesis defects, transposon
      mutagenesis was performed and mutants were selected based resistance to the pili
      tropic bacteriophage PhiCbK. Mutants were then screened for defects in motility
      and holdfast production. Only a single podJ/pleC-independent mutant was isolated
      which had defects in all three phenotypes. Directed phage assays confirmed the
      phage resistance phenotype, while the strain demonstrated a similar dispersal
      radius as a podJ mutant in swarm agar, and treatment with a fluorescent lectin
      that labels the holdfast showed no staining for this mutant. The transposon had
      inserted into the promoter region of ctrA, a gene encoding a master
      transcriptional regulator of the cell cycle, disrupting native transcription but
      still allowing reduced transcriptional activity and protein production of this
      essential protein. Transcriptional fusions showed that essential genes controlled
      by CtrA exhibited minor to moderate changes in expression in the ctrA promoter
      mutant, while the pilA gene, encoding the subunit of the pilus filament, had a
      drastic decrease in gene expression. Introduction of a plasmid-born copy of ctrA
      under its native promoter complemented the phage resistance and holdfast defects,
      as well as a moderate cell morphology defect, but not the swarming defect.
      CONCLUSIONS: A mutation was identified that caused pleiotropic defects in polar
      organelle synthesis, and revealed the surprising result that some CtrA-dependent
      promoters are more sensitive to changes in CtrA concentration than others.
      However, the fact that no pleiotropic mutations were found in new regulators
      suggests that downstream signaling of PleC/PodJ is either essential, redundant,
      or branching such that all three phenotypes were not simultaneously affected.

PMID- 23865947
TI  - Employing crisis postcards with case management in Kaohsiung, Taiwan: 6-month
      outcomes of a randomised controlled trial for suicide attempters.
AB  - BACKGROUND: Suicide attempts constitute a serious clinical problem and have
      important implications for healthcare resources. The aim of the present study was
      to evaluate the effectiveness of case management using crisis postcards over a 6
      month follow-up period. METHOD: A randomised controlled trial was conducted in
      Kaohsiung, Taiwan. Prevention of further suicide attempts was compared between
      two groups with and without the postcard intervention. The intervention group
      consisted of 373 participants (139 males, 234 females; age: 39.8 +/- 14.0 yrs.).
      The control group consisted of 388 participants (113 males, 275 females; age:
      40.0 +/- 16.0 yrs.). A survival analysis was used to test the effectiveness of
      the crisis postcard intervention for the prevention of suicide reattempts. Per
      protocol and intention-to-treat analyses were conducted. RESULTS: The intention
      to-treat analysis indicated that the crisis postcard had no effect (hazard ratio
      = 0.84; 95% CI = 0.56 - 1.29), whereas the per-protocol analysis showed a strong
      benefit for the crisis postcard (hazard ratio = 0.39; 95% CI = 0.21 - 0.72).
      CONCLUSION: Although the results of the present study indicated that the postcard
      intervention did not reduce subsequent suicide behaviour, our study provides an
      alteration to the postcard intervention. Further studies need to be conducted to
      clarify whether this type of intervention can reduce subsequent suicidal
      behaviour, with a particular focus on reducing the rate of loss to follow-up.

PMID- 23865948
TI  - Synergistic effects of mutations in cytochrome P450cam designed to mimic
      CYP101D1.
AB  - A close orthologue to cytochrome P450cam (CYP101A1) that catalyzes the same
      hydroxylation of camphor to 5-exo-hydroxycamphor is CYP101D1. There are
      potentially important differences in and around the active site that could
      contribute to subtle functional differences. Adjacent to the heme iron ligand,
      Cys357, is Leu358 in P450cam, whereas this residue is Ala in CYP101D1. Leu358
      plays a role in binding of the P450cam redox partner, putidaredoxin (Pdx). On the
      opposite side of the heme, about 15-20 A away, Asp251 in P450cam plays a critical
      role in a proton relay network required for O2 activation but forms strong ion
      pairs with Arg186 and Lys178. In CYP101D1 Gly replaces Lys178. Thus, the local
      electrostatic environment and ion pairing are substantially different in
      CYP101D1. These sites have been systematically mutated in P450cam to the
      corresponding residues in CYP101D1 and the mutants analyzed by crystallography,
      kinetics, and UV-vis spectroscopy. Individually, the mutants have little effect
      on activity or structure, but in combination there is a major drop in enzyme
      activity. This loss in activity is due to the mutants being locked in the low
      spin state, which prevents electron transfer from the P450cam redox partner, Pdx.
      These studies illustrate the strong synergistic effects on well-separated parts
      of the structure in controlling the equilibrium between the open (low-spin) and
      closed (high-spin) conformational states. 

PMID- 23865949
TI  - Domestic duck eggs: an important pathway of human exposure to PBDEs around e
      waste and scrap metal processing areas in Eastern China.
AB  - Although consumption of local foods is recognized as an important pathway of
      human exposure to PBDEs in areas of China involved in rudimentary recycling of
      electronic waste (e-waste), dietary intake studies to date have not considered
      the contribution from consumption of duck eggs, despite being a common dietary
      component. Fresh duck eggs (n = 11) were collected from each of five farms
      located within 500 m of e-waste recycling workshops in the Wenling and Luqiao
      districts of Taizhou City, Eastern China, in November 2011, along with eggs from
      a control site located 90 km to the northeast. Average SigmaPBDE yolk
      concentrations in eggs from the Taizhou farms ranged from 52.7 to 1778 ng/g lipid
      weight (8 ng/g lipid weight at the control site), at the high end of values
      previously reported for PBDEs in chicken eggs from the same locations and with
      BDE-209 predominant in over 60% of samples. Estimated typical adult daily
      SigmaPBDE intakes due to consumption of duck eggs were in the range of 159-5124
      ng/person per day. For the pentabrominated BDE-99 congener, estimated intakes
      from duck eggs alone were substantially above the no adverse effect level (NAEL)
      for impaired human spermatogenesis proposed by Netherlands researchers. 

PMID- 23865950
TI  - Developing new pharmacotherapies for autism.
AB  - Developing new pharmacotherapies for autism spectrum disorder (ASD) is a
      challenge. ASD has a complex genetic architecture, several neurobiological
      phenotypes and multiple symptom domains. However, new opportunities are emerging
      that could lead to the development of 'targeted' and individualized
      pharmacological interventions. Here, first we review these important new insights
      into the aetiology and neurobiology of ASD with particular focus on (i) genetic
      variants mediating synaptic structure and functioning and (ii) differences in
      brain anatomy, chemistry and connectivity in this condition. The characterization
      of the genotypic and phenotypic differences underlying ASD might in the future be
      invaluable for stratifying the large range of different individuals on the autism
      spectrum into genetically and/or biologically homogeneous subgroups that might
      respond to similar targeted interventions. Secondly, we propose a strategic
      framework for the development of targeted pharmacotherapies for ASD, which
      comprises several different stages in which research findings are translated into
      clinical applications. The establishment of animal models and cellular assays is
      important for developing and testing new pharmacological targets before
      initiating large-scale clinical trials. Finally, we present the European Autism
      Interventions - A Multicentre Study for Developing New Medications (EU-AIMS)
      Initiative, which was set up in the context of the EU Innovative Medicines
      Initiative as the first European platform for integrated translational research
      in ASD. The EU-AIMS Initiative consists of academic and industrial partners
      working in collaboration to deliver a more 'personalized' approach to diagnosing
      and treating ASD in the future. 

PMID- 23865951
TI  - Exploiting localized surface binding effects to enhance the catalytic reactivity
      of peptide-capped nanoparticles.
AB  - Peptide-based methods represent new approaches to selectively produce
      nanostructures with potentially important functionality. Unfortunately,
      biocombinatorial methods can only select peptides with target affinity and not
      for the properties of the final material. In this work, we present evidence to
      demonstrate that materials-directing peptides can be controllably modified to
      substantially enhance particle functionality without significantly altering
      nanostructural morphology. To this end, modification of selected residues to vary
      the site-specific binding strength and biological recognition can be employed to
      increase the catalytic efficiency of peptide-capped Pd nanoparticles. These
      results represent a step toward the de novo design of materials-directing
      peptides that control nanoparticle structure/function relationships. 

PMID- 23865952
TI  - Host-parasite coevolution favours parasite genetic diversity and horizontal gene
      transfer.
AB  - Host-parasite coevolution is predicted to favour genetic diversity and the
      underlying mechanisms (e.g. sexual reproduction and, more generally, genetic
      exchange), because diversity enhances the antagonists' potential for rapid
      adaptation. To date, this prediction has mainly been tested and confirmed for the
      host. It should similarly apply to the parasite. Indeed, our previous work
      demonstrated that experimental coevolution between the nematode Caenorhabditis
      elegans and its microparasite Bacillus thuringiensis selects for genetic
      diversity in both antagonists. For the parasite, the previous analysis was based
      on plasmid-encoded toxin gene markers. Thus, it was restricted to a very small
      part of the bacterial genome and did not cover the main chromosome, which
      harbours a large variety of virulence factors. Here, we present new data for
      chromosomal gene markers of B. thuringiensis and combine this information with
      the previous results on plasmid-encoded toxins. Our new results demonstrate that,
      in comparison with the control treatment, coevolution with a host similarly leads
      to higher levels of genetic diversity in the bacterial chromosome, thus
      indicating the relevance of chromosomal genes for coevolution. Furthermore, the
      frequency of toxin gene gain is significantly elevated during coevolution,
      highlighting the importance of horizontal gene transfer as a diversity-generating
      mechanism. In conclusion, our study emphasizes the strong influence of
      antagonistic coevolution on parasite genetic diversity and gene exchange. 

PMID- 23865953
TI  - Testing the polynuclear hypothesis: multielectron reduction of small molecules by
      triiron reaction sites.
AB  - High-spin trinuclear iron complex ((tbs)L)Fe3(thf) ([(tbs)L](6-) = [1,3,5
      C6H9(NC6H4-o-NSi(t)BuMe2)3](6-)) (S = 6) facilitates 2 and 4e(-) reduction of
      NxHy type substrates to yield imido and nitrido products. Reaction of hydrazine
      or phenylhydrazine with ((tbs)L)Fe3(thf) yields triiron MU(3)-imido cluster
      ((tbs)L)Fe3(MU(3)-NH) and ammonia or aniline, respectively. ((tbs)L)Fe3(MU(3)-NH)
      has a similar zero-field (57)Fe Mossbauer spectrum compared to previously
      reported [((tbs)L)Fe3(MU(3)-N)]NBu4, and can be directly synthesized by
      protonation of the anionic triiron nitrido with lutidinium tetraphenylborate.
      Deprotonation of the triiron parent imido ((tbs)L)Fe3(MU(3)-NH) with lithium
      bis(trimethylsilyl)amide results in regeneration of the triiron nitrido complex
      capped with a thf-solvated Li cation [((tbs)L)Fe3(MU(3)-N)]Li(thf)3. The lithium
      capped nitrido, structurally similar to the pseudo C3-symmetric triiron nitride
      with a tetrabutylammonium countercation, is rigorously C3-symmetric featuring
      intracore distances of Fe-Fe 2.4802(5) A, Fe-N(nitride) 1.877(2) A, and
      N(nitride)-Li 1.990(6) A. A similar 2e(-) reduction of 1,2-diphenylhydrazine by
      ((tbs)L)Fe3(thf) affords ((tbs)L)Fe3(MU(3)-NPh) and aniline. The solid state
      structure of ((tbs)L)Fe3(MU(3)-NPh) is similar to the series of MU(3)-nitrido and
      -imido triiron complexes synthesized in this work with average Fe-Nimido and Fe
      Fe bond lengths of 1.941(6) and 2.530(1) A, respectively. Reductive N?N bond
      cleavage of azobenzene is also achieved in the presence of ((tbs)L)Fe3(thf) to
      yield triiron bis-imido complex ((tbs)L)Fe3(MU(3)-NPh)(MU(2)-NPh), which has been
      structurally characterized. Ligand redox participation has been ruled out, and
      therefore, charge balance indicates that the bis-imido cluster has undergone a
      4e(-) metal based oxidation resulting in an (Fe(IV))(Fe(III))2 formulation.
      Cyclic voltammograms of the series of triiron clusters presented herein
      demonstrate that oxidation states up to (Fe(IV))(Fe(III))2 (in the case of
      [((tbs)L)Fe3(MU(3)-N)]NBu4) are electrochemically accessible. These results
      highlight the efficacy of high-spin, polynuclear reaction sites to cooperatively
      mediate small molecule activation. 

PMID- 23865954
TI  - Effects of hyperbaric oxygen therapy on the viability of irradiated soft head and
      neck tissues in mice.
AB  - OBJECTIVES: Hyperbaric oxygen therapy (HBOT) is used clinically in irradiation
      induced injury to healthy tissues, but the effectiveness and working mechanism
      remain unclear. This study examined the effects of HBOT on irradiated salivary
      glands and tongue in a mouse model. MATERIALS AND METHODS: Mice were irradiated
      with a single dose (15 Gy) in the head and neck region and subjected to HBOT,
      either before or after irradiation. During the course of the treatments, salivary
      flow rates were measured and at different time points after radiation (2, 6, 10
      and 24 weeks), salivary glands and tongue were harvested and (immuno)
      histochemically analysed. RESULTS: Proliferation and blood vessel density in
      salivary glands were enhanced by HBOT in the medium term (10 weeks after
      irradiation), while salivary flow rates were not influenced. In the long term,
      irradiation-induced proliferation in the muscle tissue of the tongue was
      decreased by HBOT. CONCLUSION: Hyperbaric oxygen therapy (HBOT) appears to
      stimulate regeneration or protection of salivary gland tissue following radiation
      therapy. Possible implications of the effect of HBOT on muscle tissue of the
      tongue for the prevention of dysphagia and trismus are discussed. This study
      provides insights on the cellular changes after HBOT and encourages further
      research on this topic to achieve a better implementation of the therapy in
      humans.

PMID- 23865955
TI  - Proton pump inhibitors and acute kidney injury: a nested case-control study.
AB  - BACKGROUND: Proton pump inhibitors (PPI) are a widely-used class of drugs for the
      treatment of gastro-esophageal reflux disease and other acid-related disorders of
      the gastrointestinal tract. As a class, PPIs have demonstrated a favorable safety
      profile. However, case reports have suggested that this class of drugs may be
      linked to acute kidney injury, which may in turn lead to chronic injury or
      failure. The objective of this study was to determine if an association between
      PPIs and kidney failure exists and to estimate an effect size for the
      relationship between PPI use and renal disease. METHODS: A nested case-control
      study was conducted in a privately insured population in a single Midwestern
      state including a total of 184,480 patients aged 18 years or older who were
      continuously enrolled with the insurer for at least 24 months between September
      2002 and November 2005. RESULTS: Renal disease was positively associated with PPI
      use (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.27, 2.32, p < 0.001)
      even after controlling for potential confounding conditions. After removing
      patients with potential confounding disease states from the study population, the
      number of cases (195 of the 854) and controls (607) was lower, but the
      relationship between renal disease and PPI use remained consistent (OR 2.25, CI
      1.09-4.62, p < 0.001). CONCLUSIONS: Patients with a renal disease diagnosis were
      twice as likely to have used a previous prescription for a PPI. Therefore, it is
      necessary for physicians to increase recognition of patient complaints or
      clinical manifestations of this potentially harmful event in order to prevent
      further injury.

PMID- 23865958
TI  - Implementing physician orders for life-sustaining treatment in California
      hospitals: factors associated with adoption.
AB  - Physician Orders for Life-Sustaining Treatment (POLST) is a tool to document and
      ensure continuity of end-of-life treatment decisions across healthcare settings
      that became a legal document in California in January 2009. Hospitals were
      surveyed to evaluate factors associated with uptake of this intervention and
      whether a grassroots community coalition intervention facilitated dissemination.
      A mail and telephone survey of all acute care hospitals in California was
      conducted between August 2011 and January 2012, and community coalition reports
      of interaction with hospitals and hospital characteristics from the California
      Office of Statewide Planning and Development and Census ZIP Code Tabulation Areas
      were analyzed. Of 349 hospitals, 286 (81.9%) responded to the survey. Sixty-five
      percent of hospitals had a policy about POLST, 87% had available blank POLST
      forms, 84% had educated staff, and 94% reported handling POLST properly in the
      emergency department and on admission. In multivariable analyses, hospitals in
      poor areas and for-profit (vs nonprofit) hospitals were less likely to stock
      blank POLST forms and to have educated staff, and hospitals with community
      coalition interaction and in wealthier areas were more likely to handle POLST
      forms correctly. Although POLST is widely used in California, a significant
      minority of hospitals remain unprepared 3 years after implementation. Efforts to
      improve implementation should emphasize dissemination in poorer areas and in for
      profit hospitals.

PMID- 23865959
TI  - Papilloedema associated with dural venous sinus thrombosis.
AB  - Papilloedema is a diagnostic term used exclusively to describe optic disc oedema
      associated with increased intracranial pressure. Septic cerebral venous sinus
      thrombosis has become an increasingly rare cause of papilloedema because of the
      widespread availability of antimicrobial agents; however, it is imperative for
      optometrists to maintain vigilance for this pathologic process. Presented is a
      case of a 77-year-old Caucasian male with a complaint of blurred vision and non
      specific, diffuse headache. He had a right sixth cranial nerve palsy and
      bilateral disc oedema. Raised intracranial pressure was confirmed by lumbar
      puncture. Neuroimaging, including magnetic resonance imaging and magnetic
      resonance venography in conjunction with cytological assessment of the cerebral
      spinal fluid led to a probable diagnosis of mastoiditis causing multiple dural
      venous sinus thrombi of the superior sagittal and right transverse sinuses.
      Sequential evaluation of this complex case is displayed along with pertinent
      differential diagnoses for optic disc oedema and a review of current standards
      for diagnosis and management of papilloedema from dural sinus thrombosis. 

PMID- 23865956
TI  - Sequence analyses of the distal-less homeobox gene family in East African cichlid
      fishes reveal signatures of positive selection.
AB  - BACKGROUND: Gen(om)e duplication events are hypothesized as key mechanisms
      underlying the origin of phenotypic diversity and evolutionary innovation. The
      diverse and species-rich lineage of teleost fishes is a renowned example of this
      scenario, because of the fish-specific genome duplication. Gene families,
      generated by this and other gene duplication events, have been previously found
      to play a role in the evolution and development of innovations in cichlid fishes 
      a prime model system to study the genetic basis of rapid speciation, adaptation
      and evolutionary innovation. The distal-less homeobox genes are particularly
      interesting candidate genes for evolutionary novelties, such as the pharyngeal
      jaw apparatus and the anal fin egg-spots. Here we study the dlx repertoire in 23
      East African cichlid fishes to determine the rate of evolution and the signatures
      of selection pressure. RESULTS: Four intact dlx clusters were retrieved from
      cichlid draft genomes. Phylogenetic analyses of these eight dlx loci in ten
      teleost species, followed by an in-depth analysis of 23 East African cichlid
      species, show that there is disparity in the rates of evolution of the dlx
      paralogs. Dlx3a and dlx4b are the fastest evolving dlx genes, while dlx1a and
      dlx6a evolved more slowly. Subsequent analyses of the nonsynonymous-synonymous
      substitution rate ratios indicate that dlx3b, dlx4a and dlx5a evolved under
      purifying selection, while signs of positive selection were found for dlx1a,
      dlx2a, dlx3a and dlx4b. CONCLUSIONS: Our results indicate that the dlx repertoire
      of teleost fishes and cichlid fishes in particular, is shaped by differential
      selection pressures and rates of evolution after gene duplication. Although the
      divergence of the dlx paralogs are putative signs of new or altered functions,
      comparisons with available expression patterns indicate that the three dlx loci
      under strong purifying selection, dlx3b, dlx4a and dlx5a, are transcribed at high
      levels in the cichlids' pharyngeal jaw and anal fin. The dlx paralogs emerge as
      excellent candidate genes for the development of evolutionary innovations in
      cichlids, although further functional analyses are necessary to elucidate their
      respective contribution.

PMID- 23865960
TI  - Probing local ionic dynamics in functional oxides at the nanoscale.
AB  - A scanning probe microscopy technique for probing local ionic dynamics in
      electrochemically active materials based on the first-order reversal curve
      current-voltage (FORC-IV) method is presented. FORC-IV imaging mode is applied to
      a Ca-substituted bismuth ferrite (Ca-BFO) system to separate the electronic and
      ionic phenomena in this material and visualize the spatial variability of these
      behaviors. The variable-temperature measurements further demonstrate the
      interplay between the thermally and electric-field-driven resistance changes in
      Ca-BFO. The FORC-IV is shown to be a simple, powerful, and flexible method for
      studying electrochemical activity of materials at the nanoscale and, in
      conjunction with the electrochemical strain microscopy, it can be used for
      differentiating ferroelectric and ionic behaviors. 

PMID- 23865962
TI  - Mapping of QTLs associated with biological nitrogen fixation traits in soybean.
AB  - Biological nitrogen fixation (BNF) is a key process, but despite the economic and
      environmental importance, few studies about quantitative trait loci (QTL)
      controlling BNF traits are available, even in the economically important crop
      soybean Glycine max (L.) Merr. In this study, a population of 157 F2:7 RILs
      derived from crossing soybean cultivars Bossier (high BNF capacity) and Embrapa
      20 (medium BNF capacity) was genotyped with 105 simple sequence repeat markers
      (SSRs). The genetic map obtained has 1231.2 cM and covers about 50% of the
      genome, with an average interval of 18.1 cM. Three traits, nodule number (NN),
      the ratio nodule dry weight (NDW)/NN and shoot dry weight (SDW) were used to
      evaluate BNF performance. A composite interval mapping for multiple traits method
      (mCIM) analysis mapped two QTLs for SDW (LGs E and L), three for NN (LGs B1, E
      and I), and one for NDW/NN (LG I); all QTLs were of small effect (R-values
      ranging from 1.7% to 10.0%) and explained 15.4%, 13.8% and 6.5% of total
      variation for these three traits, respectively.

PMID- 23865963
TI  - Chromosome evolution in Neotropical butterflies.
AB  - We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104
      species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a
      modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n =
      around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among
      Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n =
      26 as the most common chromosome number. Dismorphiinae show wide variation. We
      discuss these results in the context of chromosome numbers of over 1400
      Neotropical butterfly species and subspecies derived from about 3000 populations
      published here and in earlier papers of a series. The overall results show that
      many Neotropical groups are characterized by karyotype instability with several
      derived modal numbers or none at all, while almost all taxa of Lepidoptera
      studied from the other parts of the world have one of n = 29-31 as modal numbers.
      Possibly chromosome number changes become fixed in the course of speciation
      driven by biotic interactions. Population subdivision and structuring facilitate
      karyotype change. Factors that stabilize chromosome numbers include hybridization
      among species sharing the same number, migration, sexual selection and possibly
      the distribution of chromosomes within the nucleus.

PMID- 23865964
TI  - IHH gene polymorphism among three horse breeds and its application for
      association test in horses with osteochondrosis.
AB  - Genetic polymorphism of IHH gene were investigated in Angloarabian, Polish
      Coldblood and Polish Halfbred horses with the inclusion of a group of Polish
      Halfbreds affected by osteochondrosis. IHH is a good candidate gene for
      association study of developmental disorders mainly affecting skeleton
      development. DNA sequence spanning IHH gene annotated in the horse genome and its
      putative promoter were investigated using SANGER sequencing. Analysis of genetic
      variability at polymorphic sites in the IHH gene body and the promoter region
      confirmed genetic differences between warmblood and coldblood horse breeds. A
      test for allelic and genotypic association at particular SNP sites revealed no
      association with osteochondrosis in investigated group of Polish Halfbreds. It
      was concluded that participation of different warmblood breeds in pedigrees of
      Polish Halfbreds make it difficult to search for genetic variants being
      associated with this complex disorder in this breed. IHH gene polymorphism
      investigated among three different horse populations would be valuable for
      further studies on equine bone developmental disorders.

PMID- 23865965
TI  - Expression analysis of a family of developmentally-regulated cytosolic
      sulfotransferases (SULTs) in Drosophila.
AB  - We have compared the amino acid sequence of all four cytosolic sulfotransferases
      (SULTs) in Drosophila and analyzed their spatial expression patterns during
      development. Three out of four SULTs show distinct expression activity during
      embryogenesis, while the 4th SULT shows expression only post-embryonically. st1,
      st3 and st4 are expressed in non-overlapping expression domains mainly confined
      to organs of the alimentary canal such as esophagus, malphigian tubules, hindgut,
      as well as in the tracheal system. All these organs are surrounded by the
      hemolymph suggesting that Drosophila SULTs exert their function in detoxification
      of substances upon influx from the hemolymph.

PMID- 23865966
TI  - Capturing finger and palm impressions using a hand cream and thermochromatic
      paper.
AB  - An inkless set of finger and palm impressions has been obtained on
      thermochromatic paper by incorporating the protic solvent butylene glycol into a
      base hand cream mixture, which is rubbed into the hands for 30 sec before
      donation. This requires no washing of the hands before or after donation,
      removing many of the difficulties associated with inked impressions. In a random
      trial of 50 male and 50 female participants (mean age 41 years), 96 found the
      hand cream pleasant and easy to use and all produced identifiable finger and palm
      impressions. Following donation, participants continued to rub the hand cream
      into their hands. Impressions were visible immediately after donation and have
      not exhibited fading 2 years after being taken. 10% of participants produced
      impressions that captured third-level detail, the variation between participants
      being thought to be associated with the amount of pressure applied during
      donation. 

PMID- 23865969
TI  - A tribute to Dr. Helen Rehr.

PMID- 23865968
TI  - Isolation and partial characterization of a novel virus from different carp
      species suffering gill necrosis - ultrastructure and morphogenesis.
AB  - Two isolates of a novel enveloped RNA virus were obtained from carp and koi carp
      with gill necrosis. Both isolates behaved identically and could be propagated in
      different cyprinid cell lines forming large syncytia. The virus was sensitive to
      lipid solvents and neither exhibited haemadsorption/haemagglutination nor reverse
      transcriptase activity. Mature virus particles displayed a spherical shape with
      diameter of 100-350 nm after negative staining and 100-300 nm in ultrathin
      sections, covered by short projections of 8-10 nm in length. Maturation of virus
      progeny was shown to occur by budding and envelopment of the filamentous helical
      nucleocapsids at the cell surface. A detailed comparison of ultrastructure and
      morphogenesis of the novel virus isolates with selected arena-, ortho- and
      paramyxoviruses as possible candidates for evaluation of taxonomic classification
      yielded no consistency in all phenotypic features. Thus, on the basis of
      ultrastructure the novel virus isolates could not be assigned unequivocally to
      any established virus family.

PMID- 23865970
TI  - Perceived health status and health insurance status: protective factors against
      health-related debt?
AB  - Current health care debate has largely focused on the need for health insurance
      coverage rather than quality coverage. Yet the economic downturn has resulted in
      an increasing number of individuals who are uninsured or underinsured, and
      consequently face financial hardships. Multivariate analyses were used with 95
      adults to examine relationships between health insurance, health status, and
      health debt. Controlling for demographics, and human and financial capital,
      findings suggest that health debt is not related to health insurance or health
      status. However, individuals with post-secondary education and non-homeowners
      appear to be more at risk for accumulating health debt. 

PMID- 23865971
TI  - Parents' experience of their child's first psychiatric breakdown: "welcome to
      hell".
AB  - Clinicians and researchers have emphasized the importance of helping the primary
      caregivers of persons going through the first outbreak of psychiatric illness in
      order to mitigate the negative consequences of the illness on the patient and the
      caregivers. The aim of the current qualitative, retrospective study is to examine
      the experiences, challenges, and difficulties faced by Israeli parents during the
      outbreak of psychiatric illness in their children. In-depth, semi-structured
      interviews were conducted with 10 parents who participated in a psycho
      educational group in a family mental health center. Several themes regarding
      parents' experience of the first outbreak of their children's psychiatric illness
      emerge from the content analysis of the interviews--the perception of sudden
      onset of the illness, feelings of being mired in distress, intense pain stemming
      from guilt and helplessness with concomitant anger, and isolation. The themes are
      then discussed in light of the concept of ambiguous loss and the existential
      approach. The findings indicate psycho-social services in the Israeli mental
      health system provide only a partial response to the needs of parents during this
      critical period.

PMID- 23865972
TI  - Advocacy at the end of life: meeting the needs of vulnerable Latino patients.
AB  - This research explores health care professionals' understanding of the problems
      that arise in managing a terminal condition impacting the Latino population and
      conceptualizes the components of patient advocacy that address gaps in end-of
      life care for patients and their family members. Limited research exists
      regarding patient advocacy from the perspectives of health care providers working
      with vulnerable Latino populations utilizing a public sector health care system.
      Forty-six semi-structured interviews were conducted with providers from different
      disciplines including medicine, nursing, social work, and chaplaincy. Although
      roles and responsibilities vary among health providers, it is imperative that all
      providers become aware of the need for patient advocacy. Doing so is not only in
      the best interest of vulnerable Latino populations but also has overarching
      financial benefits and positive outcomes for patients, administrators, and public
      health care systems. Social workers are the ideal professionals to assume
      leadership roles and share their knowledge of how to advocate effectively for the
      most vulnerable populations. 

PMID- 23865973
TI  - Coping with sickle cell anemia in Nigerian universities: the case of Obafemi
      Awolowo University, Ile-Ife, Nigeria.
AB  - This study examined coping strategies of students living with sickle cell anemia.
      In-depth interviews were conducted on 10 students living with sickle cell anemia
      and eight were conducted on the health workers. To explain the sufferers view and
      experience, interpretative phenomenology approach was employed. Findings were
      that sufferers experience much pain and crisis. Their coping strategies include
      having plenty of rest and water, avoiding strenuous activities and taking their
      medications. They had a good knowledge of the disease but faced the challenges of
      combining caring for themselves and academic pursuit which create problems of
      adherence and finance for buying drugs and sponsoring their education at the same
      time. In conclusion, sufferers were coping well but there was still a need to
      address the problems of harsh university environment, finance and adherence. 

PMID- 23865974
TI  - The role of race and english proficiency on the health of older immigrants.
AB  - This study applies the Commission on Social Determinants of Health model to
      identify the effect of ethnicity/race and English proficiency on the health of
      older immigrants. California Health Interview Survey data of foreign-born
      respondents aged 65 and over were used to examine the four outcomes of health
      related quality of life (HRQOL). The study included 1,196 immigrant Latinos,
      Asians, and non-Hispanic Whites. The results show that ethnicity/race-based
      differences in HRQOL exist. Furthermore, the results indicate that English
      proficiency has a significant moderating relationship on racial/ethnic
      background. The likelihood of reporting more Limited Combined Days increased with
      lower levels of English proficiency for both Latino and Asian-American old adults
      as compared to non-Hispanic Whites. In addition to focusing on racial
      disparities, health promotion efforts with older immigrants need to examine
      language-based stratification. Social work and gerontological advocates need to
      develop and employ evidence-based interventions that reach limited-English
      proficient older immigrants to address the health, psychosocial, and access to
      health care challenges they face. 

PMID- 23865978
TI  - Nanostructure formation in the lecithin/isooctane/water system.
AB  - We present here for the first time a study of the self-assembled nanostructures
      in the lecithin/isooctane/water system by direct-imaging techniques, namely,
      cryogenic transmission electron microscopy (cryo-TEM) and cryogenic scanning
      electron microscopy (cryo-SEM). Along the dilution line [water]/[lecithin] = 5,
      we identified a nanostructural development with the increase of lecithin
      concentration. The system changes from a single reverse micellar phase, through a
      reverse micellar phase coexisting with a lamellar phase, and finally to a reverse
      liquid crystalline cubic phase and a lamellar phase. We compared the
      nanostructures formed when phosphatidylcholine rather than naturally occurring
      lecithin is used and found that both phase behavior and nanostructure are
      significantly different. The use of the two complementary cryo-EM techniques
      proved very efficient in the nanostructural characterization of the system. We
      also performed small-angle X-ray scattering to confirm our findings. Since the
      system is very sensitive to changes in composition, the cryo-EM specimens were
      prepared in a Controlled Environment Vitrification System (CEVS) that has been
      modified for our specimen preparation needs. We were able to overcome the
      challenges involved in directly imaging this nonaqueous (oil-rich), concentrated
      complex liquid systems, thus extending the usefulness of those characterization
      techniques. 

PMID- 23865977
TI  - Intraperitoneal insulin delivery to patients with type 1 diabetes results in
      higher serum IGF-I bioactivity than continuous subcutaneous insulin infusion.
AB  - OBJECTIVE: Type 1 diabetes (T1D) is associated with low IGF-I and altered levels
      of IGF-binding proteins (IGFBPs) in plasma. This may be of importance for insulin
      sensitivity and the risk of developing diabetic complications. We hypothesized
      that IGF-I bioactivity is affected by the route of insulin administration and
      that continuous intraperitoneal insulin infusion (CIPII) has a more pronounced
      effect than continuous subcutaneous insulin infusion (CSII). DESIGN AND METHODS:
      We compared 10 patients with T1D on CIPII with 20 age- and sex-matched patients
      on CSII. Blood sampling was carried out 7-9 am after an overnight fast. All
      patients were C-peptide negative. IGF-I bioactivity was measured in vitro using a
      specific IGF-I kinase receptor activation (KIRA) assay. IGF-I was also measured
      by immunoassay together with IGF-II, IGFBP-1 and IGFBP-2. RESULTS: When compared
      with subcutaneous insulin, intraperitoneal insulin resulted in (CIPII vs CSII)
      higher IGF-I bioactivity (1.83 +/- 0.76 vs 1.16 +/- 0.24 MUg/l; P = 0.02), IGF-I
      (120 +/- 35 vs 81 +/- 19 MUg/l; P = 0.01) and IGF-II (1050 +/- 136 vs 879 +/- 110
      MUg/l; P = 0.02). By contrast, log-transformed IGFBP-1 was reduced (P = 0.013),
      whereas log-transformed IGFBP-2 was not different (P = 0.12). There was a
      positive correlation between IGF bioactivity and IGF-I (r = 0.69; P < 0.001) and
      an inverse correlation between IGF-I bioactivity and log10 IGFBP-1 (r = -0.68, P
      < 0.001). CONCLUSION: The in vitro IGF-I bioactivity was higher in patients
      treated with CIPII compared with CSII supporting the theory that the route of
      insulin administration is of importance for the activity of the IGF system.
      Intraperitoneal insulin administration may therefore be beneficial by correcting
      the alterations of the IGF system in T1D.

PMID- 23865979
TI  - Monitoring approaches for a toxic cyanobacterial bloom.
AB  - Cyanobacterial blooms, dominated by Microcystis sp. and associated microcystin
      variants, have been implicated in illnesses of humans and animals. Little is
      known regarding the formation of blooms and the presence of cyanotoxin variants
      in water bodies. Furthermore, the role played by ecological parameters, in
      regulating Microcystis blooms is complicate and diverse. Local authorities
      responsible for water management are often faced with the challenging task of
      dealing with cyanobacterial blooms. Therefore, the development of suitable
      monitoring approaches to characterize cyanobacterial blooms is an important goal.
      Currently, various biological, biochemical and physicochemical methods/approaches
      are being used to monitor cyanobacterial blooms and detect microcystins in
      freshwater bodies. Because these methods can vary as to the information they
      provide, no single approach seemed to be sufficient to accurately monitor blooms.
      For example, immunosensors are more suited for monitoring the presence of toxins
      in clear water bodies while molecular methods are more suited to detect
      potentially toxic strains. Thus, monitoring approaches should be tailored for
      specific water bodies using methods based on economic feasibility, speed,
      sensitivity and field applicability. This review critically evaluates monitoring
      approaches that are applicable to cyanobacterial blooms, especially those that
      focus on the presence of Microcystis, in freshwater bodies. Further, they were
      characterized and ranked according to their cost, speed, sensitivity and
      selectivity. Suggested improvements were offered as well as future research
      endeavors to accommodate anticipated environmental changes. 

PMID- 23865980
TI  - Fast CO2 sequestration, activation, and catalytic transformation using N
      heterocyclic olefins.
AB  - N-Heterocyclic Olefin (NHO) with high electronegativity at the terminal carbon
      atom was found to show a strong tendency for CO2 sequestration, affording a CO2
      adduct (NHO-CO2). X-ray single crystal analysis revealed the bent geometry of the
      binding CO2 in the NHO-CO2 adducts with an O-C-O angle of 127.7-129.9 degrees ,
      dependent on the substitute groups of N-heterocyclic ring. The length of the
      C(carboxylate)-C(NHO) bond is in the range of 1.55-1.57 A, significantly longer
      than that of the C(carboxylate)-C(NHC) bond (1.52-1.53 A) of the previously
      reported NHC-CO2 adducts. The FTIR study by monitoring the nu(CO2) region of
      transmittance change demonstrated that the decarboxylation of NHO-CO2 adducts is
      easier than that of the corresponding NHC-CO2 adducts. Notably, the NHO-CO2
      adducts were found to be highly active in catalyzing the carboxylative
      cyclization of CO2 and propargylic alcohols at mild conditions (even at ambient
      temperature and 0.1 MPa CO2 pressure), selectively giving alpha-alkylidene cyclic
      carbonates in good yields. The catalytic activity is about 10-200 times that of
      the corresponding NHC-CO2 adducts at the same conditions. Two reaction paths
      regarding the hydrogen at the alkenyl position of cyclic carbonates coming from
      substrate (path A) or both substrate and catalyst (path B) were proposed on the
      basis of deuterium labeling experiments. The high activity of NHO-CO2 adduct was
      tentatively ascribed to its low stability for easily releasing the CO2 moiety
      and/or the desired product, a possible rate-limiting step in the catalytic cycle.

PMID- 23865981
TI  - Novel approaches to drug design for the treatment of schizophrenia.
AB  - INTRODUCTION: Schizophrenia is an important health issue affecting almost 1% of
      the population with significant unmet medical needs. The classical drug targets
      for the treatment of schizophrenia are dopamine D2 receptors. Second-generation
      ('atypical') drugs block more receptors of the G-protein-coupled receptor (GPCR)
      class 1 (e.g., clozapine is a D(2)-5HT(2) antagonist). AREAS COVERED: In this
      article, the author presents the new targets for GPCR as well as ligand-gated
      ion. Furthermore, the author reviews the opportunities for drug design offered by
      the structures solved recently. EXPERT OPINION: For drug design, the availability
      of these protein structures, or the possibility to build high quality models,
      allows to shift the paradigm from ligand-based to target-based drug design. The
      analysis of the drugs, both on the market and in development, shows that numerous
      targets are being considered which may reveal an ambiguity on the ideal drug
      target. This situation may be simplified, in the future, owing to recent
      integrative projects: the 'Human Brain Project' and the 'Brain Activity Map' that
      aim at modeling the brain as well as the Allen Atlas.

PMID- 23865982
TI  - Anti-retrovirals for treatment and prevention--time for new paradigms in our
      response to the HIV/AIDS epidemic?

PMID- 23865983
TI  - Ground Anthrax Bacillus Refined Isolation (GABRI) method for analyzing
      environmental samples with low levels of Bacillus anthracis contamination.
AB  - BACKGROUND: In this work are reported the results of a qualitative analytical
      method capable of detecting Bacillus anthracis spores when they are present in
      very low concentration in the soil. The Ground Anthrax Bacillus Refined Isolation
      (GABRI) method, assessed in our laboratory, was compared with the classic method.
      The comparison involved artificially anthrax-contaminated soil samples (500
      spores/7.5 grams soil) and naturally contaminated soil samples collected in
      Bangladesh during a field investigation. RESULTS: The results indicated that, in
      contrast to the classic method, the GABRI method was able to detect B.anthracis
      in all contaminated samples. The GABRI method produces a more sensitive measure
      of anthrax spore presence significantly different from the standard method. In
      particular, the latter is more sensitive to the presence of normal soil
      contaminants. CONCLUSION: The main feature of the GABRI method is its ability to
      strongly reduce the presence of the environmental contaminants, which being much
      more numerous than B. anthracis tend to inhibit their germination and growth
      making it extremely difficult to visualize any colonies. The reduction of the
      microbial environment also allows one to be able to culture and test a larger
      quantity of potentially contaminated soil and to isolate B. anthracis when the
      spores are present in very low concentrations in the soil.

PMID- 23865984
TI  - Screening high-risk patients and assisting in diagnosing anxiety in primary care:
      the Patient Health Questionnaire evaluated.
AB  - BACKGROUND: Questionnaires may help in detecting and diagnosing anxiety disorders
      in primary care. However, since utility of these questionnaires in target
      populations is rarely studied, the Patient Health Questionnaire anxiety modules
      (PHQ) were evaluated for use as: a) a screener in high-risk patients, and/or b) a
      case finder for general practitioners (GPs) to assist in diagnosing anxiety
      disorders. METHODS: A cross-sectional analysis was performed in 43 primary care
      practices in the Netherlands. The added value of the PHQ was assessed in two
      samples: 1) 170 patients at risk of anxiety disorders (or developing them)
      according to their electronic medical records (high-risk sample); 2) 141 patients
      identified as a possible 'anxiety case' by a GP (GP-identified sample). All
      patients completed the PHQ and were interviewed using the Mini International
      Neuropsychiatric interview to classify DSM-IV anxiety disorders. Psychometric
      properties were calculated, and a logistic regression analysis was performed to
      assess the diagnostic value of the PHQ. RESULTS: Using only the screening
      questions of the PHQ, the area under the curve was 83% in the high-risk sample.
      In GP-identified patients the official algorithm showed the best characteristics
      with an area under the curve of 77%. Positive screening questions significantly
      increased the odds of an anxiety disorder diagnosis in high-risk patients (odds
      ratio = 23.4; 95% confidence interval 6.9 to 78.8) as did a positive algorithm in
      GP-identified patients (odds ratio = 13.9; 95% confidence interval 3.8 to 50.6).
      CONCLUSIONS: The PHQ screening questions can be used to screen for anxiety
      disorders in high-risk primary care patients. In GP-identified patients, the
      benefit of the PHQ is less evident.

PMID- 23865985
TI  - Extensive hybridization and associated geographic trends between two rockfishes
      Sebastes vulpes and S. zonatus (Teleostei: Scorpaeniformes: Sebastidae).
AB  - Interspecific hybridization is an important evolutionary process, which has
      significant influence on the diversity within and between participating taxa.
      Although interspecific hybridization in terrestrial and freshwater organisms has
      been subjected to many detailed studies, studies in marine realm have been
      limited in terms of both numbers and detail. In this study, the potential for
      interspecific hybridization between two rockfishes, Sebastes vulpes and S.
      zonatus, occurring in the western North Pacific, was assessed on the basis of 177
      specimens collected from three sampling localities within the main geographic
      distribution of both species, and analysed using a combination of amplified
      fragment length polymorphisms (AFLP), mitochondrial DNA (mtDNA) markers and
      morphometric characters. Bayesian-based individual genetic assignment based on
      364 AFLP loci detected a total of 63 (35.6%) hybrid specimens in the data set,
      the presence of interspecific hybrids also being rigorously supported by mtDNA
      analysis using partial sequences from the control region and morphological
      analysis based on 31 morphometric characters. Hybrids from all three localities
      were found, showing a common pattern of biased introgression across the
      localities whereby hybrids were more closely related to S. zonatus than to S.
      vulpes. Apart from this common pattern, rates of hybridization varied
      considerably among the localities, being greater in the northern localities.
      Variations in the local rates of hybridization were associated with variations in
      habitat segregation and thermal regime, implying that vertical water temperature
      regimes determined the extent of habitat segregation of the two species and,
      accordingly, the opportunity for hybridization. 

PMID- 23865986
TI  - Synthesis of C-2 arylated tryptophan amino acids and related compounds through
      palladium-catalyzed C-H activation.
AB  - Tryptophan (Trp) and tryptophan derivatives are C2-arylated. A C-H activation
      process allows the preparation of both protected and unprotected arylated-Trp
      amino acids, directly from the amino acid precursor and aryl iodides. The
      obtained compounds are suitable for standard solid-phase peptide synthesis. 

PMID- 23865987
TI  - Effect of sleep position on perceived facial aging.
AB  - OBJECTIVE: To determine whether there is an association between sleep position
      and the appearance of facial wrinkles and facial descent. MATERIALS AND METHODS:
      One hundred women were questioned about their sleep position preference. An
      independent expert observer evaluated frontal images with digital laterality
      randomization to identify the side with more wrinkles and more ptosis. RESULTS:
      Forty-one right-sided sleepers and 23 left-sided sleepers were identified. There
      was statistical independence between sleep side and side with more wrinkles and
      between sleep side and side with more facial ptosis according to the Pearson chi
      square test. CONCLUSION: Sleep side preference was not significantly correlated
      with the appearance of wrinkles or facial descent.

PMID- 23865991
TI  - Some comments on the Freudian unconscious.
AB  - Freud's insight that mental processes are fundamentally unconscious is now an
      unquestioned assumption of neuroscience and cognitive psychology. Psychoanalysts
      are now faced with the question, What differentiated the psychoanalytic
      unconscious from that of other disciplines? Behind this question lies a more
      profound issue, the mind-body or mind-brain problem. It appears to be an
      insoluble paradox. Freud's concept of repression as a defense "mechanism"
      illustrates this paradox. To describe repression as a "mechanism" is to claim
      that it is analogous to a physiological process. Yet we know that repression is
      highly individualistic and subject to cultural values. In examining the Freudian
      concept of the primary process, the Noble prize-winning psychologist Daniel
      Kahneman has shown that the primary process is not wish fulfilling, as Freud
      claimed, but adaptive. The waking primary process is in the service of the
      reality principle. The growth of contemporary neuroscience has created
      challenging problems for psychoanalysis that did not exist in Freud's lifetime. 

PMID- 23865988
TI  - Analyses of the radiation of birnaviruses from diverse host phyla and of their
      evolutionary affinities with other double-stranded RNA and positive strand RNA
      viruses using robust structure-based multiple sequence alignments and advanced
      phylogenetic methods.
AB  - BACKGROUND: Birnaviruses form a distinct family of double-stranded RNA viruses
      infecting animals as different as vertebrates, mollusks, insects and rotifers.
      With such a wide host range, they constitute a good model for studying the
      adaptation to the host. Additionally, several lines of evidence link birnaviruses
      to positive strand RNA viruses and suggest that phylogenetic analyses may provide
      clues about transition. RESULTS: We characterized the genome of a birnavirus from
      the rotifer Branchionus plicalitis. We used X-ray structures of RNA-dependent RNA
      polymerases and capsid proteins to obtain multiple structure alignments that
      allowed us to obtain reliable multiple sequence alignments and we employed
      "advanced" phylogenetic methods to study the evolutionary relationships between
      some positive strand and double-stranded RNA viruses. We showed that the rotifer
      birnavirus genome exhibited an organization remarkably similar to other
      birnaviruses. As this host was phylogenetically very distant from the other known
      species targeted by birnaviruses, we revisited the evolutionary pathways within
      the Birnaviridae family using phylogenetic reconstruction methods. We also
      applied a number of phylogenetic approaches based on structurally conserved
      domains/regions of the capsid and RNA-dependent RNA polymerase proteins to study
      the evolutionary relationships between birnaviruses, other double-stranded RNA
      viruses and positive strand RNA viruses. CONCLUSIONS: We show that there is a
      good correlation between the phylogeny of the birnaviruses and that of their
      hosts at the phylum level using the RNA-dependent RNA polymerase (genomic segment
      B) on the one hand and a concatenation of the capsid protein, protease and
      ribonucleoprotein (genomic segment A) on the other hand. This correlation tends
      to vanish within phyla. The use of advanced phylogenetic methods and robust
      structure-based multiple sequence alignments allowed us to obtain a more accurate
      picture (in terms of probability of the tree topologies) of the evolutionary
      affinities between double-stranded RNA and positive strand RNA viruses. In
      particular, we were able to show that there exists a good statistical support for
      the claims that dsRNA viruses are not monophyletic and that viruses with permuted
      RdRps belong to a common evolution lineage as previously proposed by other
      groups. We also propose a tree topology with a good statistical support
      describing the evolutionary relationships between the Picornaviridae,
      Caliciviridae, Flaviviridae families and a group including the Alphatetraviridae,
      Nodaviridae, Permutotretraviridae, Birnaviridae, and Cystoviridae families.

PMID- 23865992
TI  - Some thoughts about consciousness: from a quantum mechanics perspective.
AB  - The article explores some of the basic findings of quantum physics and
      information theory and their possible usefulness in offering new vistas for
      understanding psychoanalysis and the patient-analyst interchange. Technical terms
      are explained and placed in context, and examples of applying quantum models to
      clinical experience are offered. Given the complexity of the findings of quantum
      mechanics and information theory, the article aims only to introduce some of the
      major concepts from these disciplines. Within this framework the article also
      briefly addresses the question of mind as well as the problematic of reducing the
      experience of consciousness to neurological brain functioning. 

PMID- 23865993
TI  - A theory of art and aesthetic experience.

PMID- 23865994
TI  - The maturational interpretation.

PMID- 23865995
TI  - Pasolini's Edipo Re: myth, play, and autobiography.
AB  - The pervasive influence of the Oedipus complex on world culture is a given, yet
      throughout the long history of motion pictures only one major filmmaker has
      tackled the literary source that inspired Freud. The film, Edipo Re, directed by
      Italian poet, novelist, and social and political activist Pier Paolo Pasolini,
      not only reconstructs the myth and adapts Sophocles' tragedy, but uses both as a
      basis of cinematic autobiography. This paper is a detailed analysis of the
      formal, stylistic, and thematic dimensions of this film, illustrating the complex
      manner in which Pasolini interweaves myth, play, and autobiography into a unique
      cinematic achievement. This analysis is followed by speculations on the
      implications of the film's structure and techniques and on what they reveal about
      Pasolini's character, his sexual profile, and the ignominious murder that ended
      his life. 

PMID- 23865996
TI  - On psychoanalytic supervisor competencies, the persistent paradox without
      parallel in psychoanalytic education, and dreaming of an evidence-based
      psychoanalytic supervision.

PMID- 23865999
TI  - The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic,
      tethered complex.
AB  - The E3 ubiquitin ligase CHIP (C-terminus of Hsc70 Interacting Protein, a 70 kDa
      homodimer) binds to the molecular chaperone Hsc70 (a 70 kDa monomer), and this
      complex is important in both the ubiquitination of Hsc70 and the turnover of
      Hsc70-bound clients. Here we used NMR spectroscopy, biolayer interferometry, and
      fluorescence polarization to characterize the Hsc70-CHIP interaction. We found
      that CHIP binds tightly to two molecules of Hsc70 forming a 210 kDa complex, with
      a Kd of approximately 60 nM, and that the IEEVD motif at the C-terminus of Hsc70
      (residues 642-646) is both necessary and sufficient for binding. Moreover, the
      same motif is required for CHIP-mediated ubiquitination of Hsc70 in vitro,
      highlighting its functional importance. Relaxation-based NMR experiments on the
      Hsc70-CHIP complex determined that the two partners move independently in
      solution, similar to "beads on a string". These results suggest that a dynamic C
      terminal region of Hsc70 provides for flexibility between CHIP and the chaperone,
      allowing the ligase to "search" a large space and engage in productive
      interactions with a wide range of clients. In support of this suggestion, we find
      that deleting residues 623-641 of the C-terminal region, while retaining the
      IEEVD motif, caused a significant decrease in the efficiency of Hsc70
      ubiquitination by CHIP. 

PMID- 23866000
TI  - Flow cytometry significantly improves the diagnostic value of fine needle
      aspiration cytology of lymphoproliferative lesions of salivary glands.
AB  - OBJECTIVE: Lymphoid proliferations of the salivary glands can be either reactive
      or malignant. Diagnosis based solely on fine needle aspiration (FNA) cytology may
      be troublesome in view of the difficulty in distinguishing low-grade B-cell and
      mucosa-associated lymphoid tissue (MALT) lymphomas from reactive lymphoid
      proliferations. We report our experience with FNA cytology combined with flow
      cytometry (FC) immunophenotyping for the diagnosis of lymphoproliferative
      processes affecting the salivary glands. METHODS: Sixty-one FNA specimens,
      obtained from salivary glands over a 10-year period, were analysed by cytology
      and FC. The results were correlated with histological follow-up if available.
      RESULTS: A diagnosis of lymphoma was given in 37 of 61 (61%) specimens; 22 of 61
      (36%) specimens were considered as benign/reactive or non-lymphomatous processes;
      two of 61 (3%) specimens were considered as suspicious for lymphoma on
      cytological analysis and negative on FC. Histological control was available in 23
      malignant, four non-lymphomatous and one cytologically suspicious case. Data
      obtained by the combination of cytology and FC were confirmed in all but one
      case: the case suspicious on cytology received a histological diagnosis of
      carcinoma. Four of seven cases with small populations of clonal cells (less than
      15%) were histologically confirmed as lymphoma, whereas two remain under
      surveillance and one was reactive. Correlation with histological data showed a
      sensitivity of 100% and a specificity of 83% for the combination of cytology and
      FC. CONCLUSIONS: FC is fundamental for the diagnosis of lymphoproliferative
      lesions of the salivary glands. It may solve cytologically suspicious cases and
      detect the presence of neoplastic B or T cells. This combined approach reduces
      the time to therapy and may prevent unnecessary surgical biopsies.

PMID- 23866002
TI  - Mohs moat: peripheral cutaneous margin clearance in a collaborative approach for
      aggressive and deeply invasive basal cell carcinoma.
AB  - Although Mohs micrographic surgery is the standard of care for large, aggressive
      or recurrent non-melanoma skin cancers of the head and neck, tumours that involve
      deep underlying structures (including bone, parotid gland and named nerves) are
      impractical for extirpation under local anaesthesia. Such cases are often
      referred to a head and neck surgeon, who typically relies on intraoperative
      frozen section analysis of the peripheral cutaneous margin. Here we describe the
      use of the Mohs moat technique as part of a collaborative approach for the
      treatment of aggressive and deeply invasive basal cell carcinoma that allows an
      analysis of the complete peripheral cutaneous margin and results in decreased
      operating room and general anaesthesia time. 

PMID- 23866001
TI  - Ecto- and endoparasite induce similar chemical and brain neurogenomic responses
      in the honey bee (Apis mellifera).
AB  - BACKGROUND: Exclusion from a social group is an effective way to avoid parasite
      transmission. This type of social removal has also been proposed as a form of
      collective defense, or social immunity, in eusocial insect groups. If parasitic
      modification of host behavior is widespread in social insects, the underlying
      physiological and neuronal mechanisms remain to be investigated. We studied this
      phenomenon in honey bees parasitized by the mite Varroa destructor or
      microsporidia Nosema ceranae, which make bees leave the hive precociously. We
      characterized the chemical, behavioral and neurogenomic changes in parasitized
      bees, and compared the effects of both parasites. RESULTS: Analysis of cuticular
      hydrocarbon (CHC) profiles by gas chromatography coupled with mass
      spectrophotometry (GC-MS) showed changes in honey bees parasitized by either
      Nosema ceranae or Varroa destructor after 5 days of infestation. Levels of 10
      HDA, an antiseptic important for social immunity, did not change in response to
      parasitism. Behavioral analysis of N. ceranae- or V. destructor- parasitized bees
      revealed no significant differences in their behavioral acts or social
      interactions with nestmates. Digital gene expression (DGE) analysis of
      parasitized honey bee brains demonstrated that, despite the difference in
      developmental stage at which the bee is parasitized, Nosema and Varroa-infested
      bees shared more gene changes with each other than with honey bee brain
      expression gene sets for forager or nurse castes. CONCLUSIONS: Parasitism by
      Nosema or Varroa induces changes to both the CHC profiles on the surface of the
      bee and transcriptomic profiles in the brain, but within the social context of
      the hive, does not result in observable effects on her behavior or behavior
      towards her. While parasitized bees are reported to leave the hive as foragers,
      their brain transcription profiles suggest that their behavior is not driven by
      the same molecular pathways that induce foraging behavior.

PMID- 23866003
TI  - Left ventricular pseudoaneurysm following transfemoral aortic valve implantation.
AB  - In spite of being a less-invasive technique, transcatheter aortic valve
      implantation (TAVI) remains associated with potential serious complications. Left
      ventricular pseudoaneurysm (LVP) is a known, serious complication of transapical
      TAVI. However, this complication has not been described after the trans-femoral
      approach. We describe a case of LVP after transfemoral TAVI, emphasizing the
      importance of an immediate diagnosis of this potential life-threatening
      complication.

PMID- 23866007
TI  - Investigation of possible presence of infectious myonecrosis virus in shrimp in
      China.

PMID- 23866006
TI  - Inverse associations between light-to-moderate alcohol intake and lipid-related
      indices in patients with diabetes.
AB  - BACKGROUND: Dyslipidemia is a common complication in patients with diabetes and
      is involved in being prone to cardiovascular disease. The risk of coronary artery
      disease is known to be lower in light-to-moderate drinkers than in abstainers.
      The aim of this study was to clarify whether and how alcohol drinking influences
      the lipid-related indices, good predictors for cardiovascular disease, such as
      the ratio of LDL cholesterol to HDL cholesterol (LDL-C/HDL-C ratio), the ratio of
      triglycerides to HDL cholesterol (TG/HDL-C ratio), and the lipid accumulation
      product (LAP), in patients with diabetes. METHODS: The subjects were men with
      diabetes (n = 1477; mean age, 54.0 years) and they were divided into non-, light
      (< 22 g ethanol/day), moderate (>= 22 and < 44 g ethanol/day) and heavy (>= 44 g
      ethanol/day) drinkers. The relationships between alcohol intake and the lipid
      related indices were investigated by the multivariate analyses with adjustment
      for age, smoking, regular exercise and drug therapy for diabetes. RESULTS: The
      odds ratio (OR) vs. nondrinkers for high LDL-C/HDL-C ratio tended to be lower
      with an increase in alcohol intake (OR with 95% confidence interval (CI): 0.80
      [0.50-1.29] in light drinkers; 0.24 [0.15-0.38] in moderate drinkers and 0.10
      [0.05-0.19] in heavy drinkers). Alcohol intake showed an inverse association with
      a high TG/HDL-C ratio (OR with 95% CI vs. nondrinkers for high TG/HDL-C ratio:
      0.54 [0.36-0.80] in light drinkers; 0.73 [0.56-0.97] in moderate drinkers and
      0.72 [0.53-0.98] in heavy drinkers) and a J-shaped relationship with a high LAP
      (OR with 95% CI vs. nondrinkers for high LAP: 0.66 [0.43-1.02] in light drinkers;
      0.82 [0.61-1.10] in moderate drinkers, and 1.29 [0.95-1.77] in heavy drinkers).
      Similar associations between alcohol intake and the lipid indices were obtained
      in a covariance analysis. CONCLUSIONS: In patients with diabetes, light-to
      moderate alcohol consumption is inversely associated with lipid-related indices,
      and this correlates with previous findings of cardiovascular risk reduction by
      modest drinking in patients with diabetes.

PMID- 23866008
TI  - Forensic or archaeological issue: is chemical analysis of dental restorations
      helpful in assessing time since death and identification of skeletonized human
      remains?
AB  - In 2011, small mass grave with completely skeletonized remains was discovered in
      Belgrade suburb. An eyewitness claimed that skeletons belonged to German soldiers
      killed in WWII. Anthropologists were engaged to investigate whether the skeletal
      remains correspond to the indicated German group or represent more recent case
      requiring court trial. Numerous dental restorations were noticed. Owing to the
      fact that different dental materials were used in dental practice at certain
      times, the aim of this study was to explore whether analysis of dental
      restorations could help in identification and estimation of time since death.
      Inductively coupled plasma optical emission spectrometry revealed that dental
      fillings corresponded to copper amalgam, conventional silver amalgam,
      silicophosphate cement, and zinc phosphate cement. Chemical results combined with
      anthropological and historical facts suggest that the individuals lived before
      the 1960s in country with well-developed dental service at that time. Therefore,
      chemical analysis of dental fillings was useful to distinguish between skeletal
      remains that are too old to be of forensic interest and the remains relevant to
      legal investigations. 

PMID- 23866011
TI  - Comparative evaluation of ethanolic extracts of Bacopa monnieri, Evolvulus
      alsinoides, Tinospora cordifolia and their combinations on cognitive functions in
      rats.
AB  - The effects of ethanolic extracts of whole plants of Bacopa monnieri (BME),
      Evolvulus alsinoides (EAE), Tinospora cordifolia (TCE) and their combinations in
      equal proportion [CEP-1 (BME+EAE), CEP-2 (BME+TCE), CEP-3 (EAE+TCE) and CEP-4
      (BME+EAE+TCE)] were tested in amnesic rats using Radial arm maze task performance
      (RAM) and Barnes maze test at 200 mg/kg p.o. The latency to find food and target
      hole was observed in RAM and Barnes maze respectively. Cognitive dysfunction was
      induced by scopolamine (0.3 mg/kg i.p.) treatment. BME, EAE, TCE and their
      combinations of equal proportion (CEPs) showed significant decrease in latency to
      find food and target hole in RAM and Barnes maze respectively. Inter comparison
      among single extract alone treated groups revealed that BME treated animals
      showed significant difference as compared to EAE and TCE treated animals. All
      combinations of equal proportion (CEPs) of these extracts showed significant
      difference in latency to find food and target hole as compared to single extracts
      treated animals. CEP-1 showed significantly better effect as compared to CEP-2
      and CEP-3. Significant difference in latency to find food and target hole was
      also present between CEP-2 and CEP-3. Effect of CEP-4 was found to be
      significantly better than CEP-1, CEP-2 and CEP-3 treated rats in both models.
      From present investigation, it was concluded that ethanolic extract of Bacopa
      monnieri, Evolvulus alsinoides and Tinospora cordifolia provided better nootropic
      effect when used in combination. 

PMID- 23866010
TI  - Relative contribution of biomolecules in bacterial extracellular polymeric
      substances to disinfection byproduct formation.
AB  - In this study, detailed chemical compositions of the biomolecules in
      extracellular polymeric substances (EPS) from both pure cultures of bacteria and
      mixed species biofilm isolated from a water utility were analyzed. Then, based on
      detailed EPS analysis results, the DBP yield experiments were conducted with both
      extracted EPS and surrogate chemicals to indirectly identify the influence of
      biomolecules and their structures on DBP formation and speciation. DBP yield
      results of both extracted EPS and EPS surrogates indicated that proteins in EPS
      have a greater influence on DBP formation, especially on the formation of
      nitrogenous DBPs (N-DBPs), where amino acids containing unsaturated organic
      carbon or conjugated bonds in R-group produced higher amount of DBPs. For
      regulated DBPs, HAA yields were higher than THM yields, while haloacetonitriles
      were the dominant DBP species formed among unregulated DBPs. However, DBP yields
      of polysaccharide monomers were lower than those of tested amino acids groups and
      the DBP yields of polysaccharide monomers were not significantly influenced by
      their structures. Considering the results obtained in this study, biofilm needs
      to be considered an important precursor to DBP formation and biofilm eradication
      methods for water distribution systems need to be carefully selected to minimize
      subsequent DBP formation. 

PMID- 23866009
TI  - Group 2 innate lymphoid cells in lung inflammation.
AB  - Although allergic asthma is a heterogeneous disease, allergen-specific T helper 2
      (Th2) cells producing the key cytokines involved in type 2 inflammation,
      interleukin-4 (IL-4), IL-5 and IL-13, are thought to play a major role in asthma
      pathogenesis. This model is challenged by the recent discovery of group 2 innate
      lymphoid cells (ILC2) that represent a critical innate source of type 2
      cytokines. These ILC2 are activated by epithelial cell-derived cytokines,
      including IL-25 and IL-33, which have been implicated in the initiation of
      asthma. In this review, we will discuss recent studies supporting a significant
      role for ILC2 in lung inflammation, with special attention to allergen-induced
      asthma. 

PMID- 23866012
TI  - Iron and iron chelators: a review on potential effects on skin aging.
AB  - Similar to oxygen, iron is essential for aerobic life and energy production. Akin
      to oxygen, iron can be toxic and accelerate the aging process. Indeed, via the
      Fenton and Haber Weiss reactions, iron potentiates the generation of highly
      reactive oxygen free radicals such as hydroxyl radical, thus stimulating
      oxidative damage. The possibility that women's longer life span relates to a
      lower iron status due to iron loss during reproductive life has been considered
      as a valid hypothesis, while hemochromatosis has been proposed as a model of iron
      overload to examine the effects of iron on the aging process. Iron plays an
      aggravating role in many diseases in which iron deprivation has been shown to be
      beneficial including ischaemia-reperfusion injury, neurological disorders and
      muscle diseases such as Duchenne's muscular dystrophy. In the skin, excess iron
      combined with UV radiation exerts pro-oxidant effects while scavenging of free
      iron prevents or inhibits the toxic effects of UV radiation on both nude mice and
      human skin. In this review, we propose that iron chelators and/or iron
      deprivation might play a significant role in the prevention of aging- associated
      diseases and conditions, in particular in the skin, and increase quality of life.
      Controlled iron deprivation might be achieved by regular blood donation in which
      case the quality of life of both the donor and the recipient is improved.
      Increasing the frequency of blood donation may thus significantly contribute to
      both individual and social wellbeing. Furthermore, we propose the skin as an
      accessible model for the study of aging and the effects of iron / iron
      deprivation on the aging mechanisms. Finally, we suggest that the development of
      topical iron chelators might represent a novel and simple approach to prevent
      skin aging, when such prevention has proven an important factor in increasing an
      aging populations' quality of life. 

PMID- 23866013
TI  - Nonplanar tertiary amides in rigid chiral tricyclic dilactams. Peptide group
      distortions and vibrational optical activity.
AB  - We investigate amide nonplanarity in vibrational optical activity (VOA) spectra
      of tricyclic spirodilactams 5,8-diazatricyclo[6,3,0,0(1,5)]undecan-4,9-dione (I)
      and its 6,6',7,7'-tetradeuterio derivative (II). These rigid molecules constrain
      amide groups to nonplanar geometries with twisted pyramidal arrangements of bonds
      to amide nitrogen atoms. We have collected a full range vibrational circular
      dichroism (VCD) and Raman optical activity (ROA) spectra including signals of C-H
      and C-D stretching vibrations. We report normal-mode analysis and a comparison of
      calculated to experimental VCD and ROA. The data provide band-to-band assignment
      and offer a possibility to evaluate roles of constrained nonplanar tertiary amide
      groups and rigid chiral skeletons. Nonplanarity shows as single-signed VCD and
      ROA amide I signals, prevailing the couplets expected to arise from the amide
      amide interaction. Amide-amide coupling dominates amide II (mainly C'-N
      stretching, modified in tertiary amides by the absence of a N-H bond) transitions
      (strong couplet in VCD, no significant ROA) probably due to the close proximity
      of amide nitrogen atoms. At lower wavenumbers, ROA spectra exhibit another likely
      manifestation of amide nonplanarity, showing signals of amide V (delta(oop)(N-C)
      at ~570 cm(-1)) and amide VI (delta(oop)(C'?O) at ~700 cm(-1) and ~650 cm(-1))
      vibrations.

PMID- 23866014
TI  - Smoking influence on sperm vitality, DNA fragmentation, reactive oxygen species
      and zinc in oligoasthenoteratozoospermic men with varicocele.
AB  - This study aimed to assess the influence of smoking duration and intensity on
      sperm vitality, sperm DNA fragmentation, reactive oxygen species (ROS) and zinc
      (Zn) levels in oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). A
      total of 246 men were investigated who were divided into OAT nonsmokers, OAT
      smokers, OAT nonsmokers and OAT smokers with Vx. They were subjected to history
      taking, clinical examination and semen analysis. In their semen, sperm hypo
      osmotic swelling (HOS) test, sperm DNA fragmentation test, seminal ROS and
      seminal Zn were assessed. The results demonstrated significantly decreased HOS
      test, seminal Zn level and significantly increased sperm DNA fragmentation,
      seminal ROS levels in OAT smokers with Vx more than OAT smokers compared with OAT
      nonsmokers. Smoking intensity, smoking duration and Vx grade demonstrated
      significant negative correlations with sperm motility, HOS test percentage and
      significant positive correlations with sperm DNA fragmentation, seminal ROS
      level. It is concluded that smoking has a negative impact on sperm progressive
      motility, HOS test, seminal Zn and positive impact on sperm DNA fragmentation,
      semen ROS level that are exaggerated if Vx is associated being correlated with
      smoking intensity, smoking duration and Vx grade.

PMID- 23866015
TI  - Cosmetic procedures performed in the United States: a 16-year analysis.
AB  - BACKGROUND: Cosmetic procedures, particularly those that are minimally invasive,
      are in demand. The physician specialties performing these procedures are not well
      characterized. OBJECTIVE: To examine changes in the frequency of cosmetic
      dermatologic procedures performed in the United States from 1995 to 2010 and the
      physician specialties performing them. METHODS: The volume of cosmetic procedures
      performed by physician specialties and the types of cosmetic procedures performed
      were determined from data from the National Ambulatory Medical Care Survey
      (NAMCS) from 1995 to 2010. RESULTS: Cosmetic procedures constituted 8.7% of all
      skin procedures and have increased since 1995 (p < .001). Botulinum toxin
      injections were the most frequently performed cosmetic procedure and increased at
      the greatest rate over time. Plastic surgeons performed the largest proportion of
      cosmetic procedures (36.1%), followed by dermatologists (33.7%), but other
      specialties have been performing an increasing proportion of cosmetic procedures.
      This study was limited to the provision of outpatient procedures, and the
      nationally representative data of the NAMCS is subject to sample bias.
      CONCLUSIONS: Plastic surgeons and other physicians performed the majority of
      outpatient cosmetic procedures. Dermatologists performed one-third of ambulatory
      cosmetic procedures from 1995 to 2010. This broadening spectrum of physicians and
      nonphysicians providing cosmetic procedures may have important implications for
      patient safety.

PMID- 23866016
TI  - Indirect costs associated with metastatic breast cancer.
AB  - OBJECTIVE: To compare the indirect costs of productivity loss between metastatic
      breast cancer (MBC) and early stage breast cancer (EBC) patients, as well as
      their respective family members. METHODS: The MarketScan Health and Productivity
      Management database (2005-2009) was used. Adult BC patients eligible for employee
      benefits of sick leave and/or short-term disability were identified with ICD-9
      codes. Difference in sick leave and short-term disability days was calculated
      between MBC patients and their propensity score matched EBC cohort and general
      population (controls) during a 12-month follow-up period. Generalized linear
      models were used to examine the impact of MBC on indirect costs to patients and
      their families. RESULTS: A total of 139 MBC, 432 EBC, and 820 controls were
      eligible for sick leave and 432 MBC, 1552 EBC, and 4682 controls were eligible
      for short-term disability (not mutually exclusive). After matching, no
      statistical difference was found in sick leave days and the associated costs
      between MBC and EBC cohorts. However, MBC patients had significantly higher short
      term disability costs than EBC patients and controls (MBC: $6166 +/- $9194 vs.
      EBC: $3690 +/- $6673 vs. CONTROLS: $558 +/- $2487, both p < 0.001). MBC patients
      had more sick leave cost than controls ($2383 +/- $5539 vs. $1282 +/- $2083, p <
      0.05). Controlling for covariates, MBC patients incurred 47% more short-term
      disability costs vs EBC patients (p = 0.009). Older patients (p = 0.002), non-HMO
      payers (p < 0.05), or patients not receiving chemotherapy during follow-up (p <
      0.001) were associated with lower short-term disability costs. MBC patients'
      families incurred 39.7% (p = 0.06) higher indirect costs compared to EBC
      patients' families after controlling for key covariates. CONCLUSION: Productivity
      loss and associated costs in MBC patients are substantially higher than EBC
      patients or the general population. These findings underscore the economic burden
      of MBC from a US societal perspective. Various treatment regimens should be
      evaluated to identify opportunities to reduce the disease burden from the
      societal perspective.

PMID- 23866017
TI  - Comparably high retention and low relapse rates in different subpopulations of
      bipolar patients in a German non-interventional study.
AB  - BACKGROUND: Although a range of pharmacotherapeutical options are available for
      the treatment of bipolar disorder, patient non-adherence to prescribed treatment
      regimens and early treatment discontinuation remain among the primary obstacles
      to effective treatment. Therefore, this observational study assessed time on mood
      stabilizing medication and retention rates in patients with bipolar disorder
      (BD). METHODS: In an 18-month, prospective, multicenter, non-interventional study
      conducted in Germany 761 outpatients (>=18 years) with BD and on maintenance
      therapy were documented. For analysis, patients were stratified by baseline
      medication: monotherapy olanzapine (OM, N = 186), lithium (LM, N = 152),
      anticonvulsants (N = 216), other mood stabilizing medication (OMS, N = 44);
      combination therapy olanzapine/lithium (N = 47), olanzapine/anticonvulsant (N =
      68), other combinations (OC, N = 48). Continuation on medication was assessed as
      retention rates with 95% confidence intervals. Time to discontinuation and
      relapse-free time were calculated by Kaplan-Meier analysis. A relapse was defined
      as increase to CGI-BP >3, worsening of CGI-BP by >=2 points, hospitalization or
      death related to BD. A Cox regression was calculated for the discontinuation of
      mood stabilizing therapy (reference: OM). Logistic regression models with
      stepwise forward selection were used to explore possible predictors of
      maintenance of treatment and relapse. RESULTS: After 540 days (18 months), the
      overall retention rate of baseline medication was 87.7%, without notable
      differences between the cohorts. The overall mean time on mood stabilizing
      treatment was 444.7 days, with a range of 377.5 (OMS) to 481 (LM) by cohort.
      74.0% of all patients were without relapse, with rates between the cohorts
      ranging from 58.4% (OC) to 80.2% (LM). CONCLUSIONS: Retention rates exceeded
      controlled trial results in all treatment cohorts, in addition to other
      explanations possibly reflecting that the physicians were expertly adapting
      treatment regimens to the individual patient's disease characteristics and
      special needs.

PMID- 23866018
TI  - Detection of new SHV-12, SHV-5 and SHV-2a variants of extended spectrum beta
      lactamase in Klebsiella pneumoniae in Egypt.
AB  - BACKGROUND: Klebsiella pneumoniae outbreaks possessing extended-spectrum beta
      lactamase- (ESBL) mediated resistance to third-generation cephalosporins have
      increased significantly in hospital and community settings worldwide. The study
      objective was to characterize prevalent genetic determinants of TEM, SHV and CTX
      M types ESBL activity in K. pneumoniae isolates from Egypt. METHODS: Sixty five
      ESBL-producing K. pneumoniae strains, isolated from nosocomial and community
      acquired infections from 10 Egyptian University hospitals (2000-2003), were
      confirmed with double disc-synergy method and E-test. blaTEM, blaSHV and blaCTX-m
      genes were identified by PCR and DNA sequencing. Pulsed-field gel electrophoresis
      (PFGE) was conducted for genotyping. RESULTS: All isolates displayed ceftazidime
      and cefotaxime resistance. blaTEM and blaSHV genes were detected in 98% of the
      isolates' genomes, while 11% carried blaCTX-m. DNA sequencing revealed plasmid
      borne SHV-12,-5,-2a (17%), CTX-m-15 (11%), and TEM-1 (10%) prevalence. Among SHV
      12 (n=8), one isolate displayed 100% blaSHV-12 amino acid identity, while others
      had various point mutations: T17G (Leu to Arg, position 6 of the enzyme: n=2);
      A8T and A10G (Tyr and Ile to Phe and Val, positions 3 and 4, respectively: n=4),
      and; A703G (Lys to Glu 235: n=1). SHV-5 and SHV-2a variants were identified in
      three isolates: T17G (n=1); A703G and G705A (Ser and Lys to Gly and Glu: n=1);
      multiple mutations at A8T, A10G, T17G, A703G and G705A (n=1). Remarkably, 57% of
      community-acquired isolates carried CTX-m-15. PFGE demonstrated four distinct
      genetic clusters, grouping strains of different genetic backgrounds. CONCLUSIONS:
      This is the first study demonstrating the occurrence of SHV-12, SHV-5 and SHV-2a
      variants in Egypt, indicating the spread of class A ESBL in K. pneumoniae through
      different mechanisms.

PMID- 23866019
TI  - Substrate specificity, processivity, and kinetic mechanism of protein arginine
      methyltransferase 5.
AB  - Protein arginine methyltransferases (PRMTs) have emerged as attractive
      therapeutic targets for heart disease and cancers. PRMT5 is a particularly
      interesting target because it is overexpressed in blood, breast, colon, and
      stomach cancers and promotes cell survival in the face of DNA damaging agents. As
      the only known member of the PRMT enzyme family to catalyze the formation of mono
      and symmetrically dimethylated arginine residues, PRMT5 is also mechanistically
      unique. As a part of a program to characterize the mechanisms and regulation of
      the PRMTs and develop chemical probes targeting these enzymes, we characterized
      the substrate specificity, processivity, and kinetic mechanism of bacterially
      expressed Caenorhabditis elegans PRMT5 (cPRMT5). In this report, we demonstrate
      that distal positively charged residues contribute to substrate binding in a
      synergistic fashion. Additionally, we show that cPRMT5 catalyzes symmetric
      dimethylation in a distributive fashion. Finally, the results of initial
      velocity, product, and dead-end inhibition studies indicate that cPRMT5 uses a
      rapid equilibrium random mechanism with dead-end EAP and EBQ complexes. In total,
      these studies will guide PRMT5 inhibitor development and lay the foundation for
      studying how the activity of this medically relevant enzyme is regulated. 

PMID- 23866020
TI  - Biocatalytic synthesis of pikromycin, methymycin, neomethymycin, novamethymycin,
      and ketomethymycin.
AB  - A biocatalytic platform that employs the final two monomodular type I polyketide
      synthases of the pikromycin pathway in vitro followed by direct appendage of D
      desosamine and final C-H oxidation(s) in vivo was developed and applied toward
      the synthesis of a suite of 12- and 14-membered ring macrolide natural products.
      This methodology delivered both compound classes in 13 steps (longest linear
      sequence) from commercially available (R)-Roche ester in >10% overall yields.

PMID- 23866021
TI  - Plasma concentration of cis9trans11 CLA in males and females is influenced by
      SCD1 genetic variations and hormonal contraceptives: a cross-sectional study.
AB  - BACKGROUND: The conjugated linoleic acid isomer cis9trans11 CLA can be
      endogenously synthesized from trans vaccenic acid (C18:1 t11) via desaturation at
      the delta 9 position catalyzed by the stearoyl-CoA desaturase 1 (SCD1), also
      known as delta-9 desaturase (D9D). Diet, hormonal regulation of gene expression
      and single nucleotide polymorphisms (SNPs) have been implicated in altering
      circulating levels of fatty acids. Hormonal contraceptives (HC) have also been
      shown to influence levels of some fatty acids. SNPs in SCD1 have been associated
      with altered levels of palmitoleic and oleic acids; however, associations between
      SCD1 SNPs and D9D desaturation index have not been previously examined in
      relation to CLA. Herein, we investigated the effects of sex and HC use on
      circulating concentrations of c9t11 CLA and D9D desaturation index. Furthermore,
      we determined the effects of ten SCD1 SNPs on D9D desaturation indices estimated
      by product to precursor ratio of c9t11 CLA to C18:1 t11. METHODS: PLASMA SAMPLES
      WERE COLLECTED FROM SUBJECTS (CAUCASIAN MALES: n = 113; Caucasian females: n =
      298; Asian males: n = 98; Asian females: n = 277) from the Toronto Nutrigenomics
      and Health Study. Circulating fatty acids levels were measured by gas
      chromatography. RESULTS: Results show that circulating c9t11 CLA concentrations
      are significantly higher in females than males and they are further elevated in
      females using HC. In addition, a significant sex- and ethnic-specific association
      was found between SCD1 SNP rs10883463 (p = 0.0014) and altered D9D activity in
      Caucasian males. CONCLUSION: Findings from the present study identify SCD1 SNPs
      and hormonal contraceptives as factors altering endogenous c9t11 CLA levels in a
      sex- and ethnic-specific manner.

PMID- 23866022
TI  - Association between serum adipocyte fatty-acid binding protein concentrations,
      left ventricular function and myocardial perfusion abnormalities in patients with
      coronary artery disease.
AB  - BACKGROUND: Adipokines, including adipocyte fatty acid-binding protein (A-FABP),
      have been demonstrated to be involved in the pathogenesis of atherosclerosis. In
      the present study, we investigated the association of circulating A-FABP level
      with severity of myocardial perfusion abnormalities analyzed by Tl-201
      dipyridamole single-photon emission computed tomography. METHODS: A total of 170
      patients with coronary artery disease (CAD) from cardiovascular clinics were
      enrolled in the study. Serum A-FABP levels, echocardiography, and stress
      myocardial perfusion imaging results were analyzed. RESULTS: Compared with the
      patients with mild CAD (summed stress score [SSS] <= 8), those with moderate to
      severe CAD (SSS > 8) had significantly higher A-FABP concentrations. However, the
      difference was attenuated in the subgroup of patients with heart failure. In the
      correlation analyses, A-FABP level was correlated with age, body mass index,
      waist circumference, levels of creatinine, fasting glucose, high-sensitivity C
      reactive protein, N-terminal pro-brain natriuretic peptide, adiponectin, and
      several echocardiographic parameters, including left ventricular ejection
      fraction. Multivariate logistic regression analysis demonstrated that the A-FABP
      level was not only associated with higher SSS (odds ratio, 1.30; 95% confidence
      interval [CI], 1.01-1.69; P = 0.048), but also an independent risk factor for
      heart failure (odds ratio 2.71, 95% CI, 1.23-5.94; P = 0.013). CONCLUSIONS: Serum
      A-FABP levels not only were associated with myocardial perfusion abnormalities
      and left ventricular function, but also predicted the presence of heart failure
      in our patients with CAD.

PMID- 23866023
TI  - Genotypic effect of ahFAD2 on fatty acid profiles in six segregating peanut
      (Arachis hypogaea L) populations.
AB  - BACKGROUND: Fatty acid composition of oil extracted from peanut (Arachis hypogaea
      L.) seed is an important quality trait because it may affect the flavor and shelf
      life of resulting food products. In particular, a high ratio of oleic (C18:1)
      relative to linoleic (C18:2) fatty acid (O/L >= 10) results in a longer shelf
      life. Previous reports suggest that the high oleic (~80%) trait was controlled by
      recessive alleles of ahFAD2A and ahFAD2B, the former of which is thought to have
      a high frequency in US runner- and virginia-type cultivars. Functional mutations,
      G448A in ahFAD2A and 442insA in ahFAD2B eliminate or knock down desaturase
      activity and have been demonstrated to produce peanut oil with high O/L ratios.
      In order to employ marker assisted selection (MAS) to select a high oleic disease
      resistant peanut and to evaluate genotypic and phenotypic variation, crosses were
      made between high oleic (~80%) and normal oleic (~50%) peanuts to produce
      segregating populations. RESULTS: A total of 539 F2 progenies were randomly
      selected to empirically determine each ahFAD2 genotype and the resulting fatty
      acid composition. Five of the six crosses segregated for the high oleic trait in
      a digenic fashion. The remaining cross was consistent with monogenic segregation
      because both parental genotypes were fixed for the ahFAD2A mutation. Segregation
      distortion was significant in ahFAD2A in one cross; however, the remaining
      crosses showed no distortion. Quantitative analyses revealed that dominance was
      incomplete for the wild type allele of ahFAD2, and both loci showed significant
      additive effects. Oleic and linoleic acid displayed five unique phenotypes, based
      on the number of ahFAD2 mutant alleles. Further, the ahFAD2 loci did exhibit
      pleiotropic interactions with palmitic (C16:0), oleic (C18:1), linoleic (C18:2)
      acids and the O/L ratio. Fatty acid levels in these progeny were affected by the
      parental genotype suggesting that other genes also influence fatty acid
      composition in peanut. As far as the authors are aware, this is the first study
      in which all of the nine possible ahFAD2 genotypes were quantitatively measured.
      CONCLUSIONS: The inheritance of the high oleic trait initially was suggested to
      be controlled by dominant gene action from two homoeologous genes (ahFAD2A and
      ahFAD2B) exhibiting complete recessivity. Analyzing the ahFAD2 genotypes and
      fatty acid compositions of these segregating peanut populations clearly
      demonstrated that the fatty acid contents are quantitative in nature although
      much of the variability in the predominant fatty acids (oleic, linoleic, and
      palmitic) is controlled by only two loci.

PMID- 23866024
TI  - Growth inhibition of an Araucaria angustifolia (Coniferopsida) fungal seed
      pathogen, Neofusicoccum parvum, by soil streptomycetes.
AB  - BACKGROUND: Araucariaceae are important forest trees of the southern hemisphere.
      Life expectancy of their seedlings can largely be reduced by fungal infections.
      In this study we have isolated and characterized such a fungus and investigated
      the potential of Streptomyces Actinobacteria from the respective rhizosphere to
      act as antagonists. RESULTS: The pathogenic fungus from Araucaria angustifolia
      seeds was identified by morphological markers (pore-associated Woronin-bodies) as
      belonging to the Pezizomycotina. Molecular data identified the fungus as
      Neofusicoccum parvum (Botryosphaeriaceae). Co-cultures on agar of this fungus
      with certain streptomycete isolates from the rhizosphere, and from the surface of
      Araucaria roots significantly reduced the growth of the fungus. HPLC analysis of
      the agar yielded streptomycete-specific exudate compounds which were partly
      identified. There were differences in compounds between single (bacteria, fungus)
      and dual cultures (bacteria + fungus). CONCLUSION: Streptomycetes from the
      rhizosphere of Araucariaceae produce exudates which can suppress the development
      of pathogenic fungi in their seeds.

PMID- 23866026
TI  - PPARgamma and PPARGC1B polymorphisms modify the association between phthalate
      metabolites and breast cancer risk.
AB  - CONTEXT: Breast cancer (BC) risk has been differentially associated with urinary
      levels of some phthalate metabolites. OBJECTIVE: To investigate whether PPARgamma
      and PPARGC1B polymorphisms modulate these associations. MATERIALS AND METHODS:
      208 BC cases were age-matched with 220 population controls. Phthalate metabolites
      were determined by HPLC-MS. PPARgamma Pro12Ala (rs1801281) and PPARGC1B Ala203Pro
      (rs7732671) and Val279Ile (rs17572019) were genotyped. RESULTS: The association
      between mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and BC risk was
      positively modified in PPARgamma Pro12Ala C carriers. The association with mono
      iso-butyl phthalate (MiBP) in PPARGC1B Ala203Pro G carriers was negatively
      modified. CONCLUSION: PPARgamma and PPARGC1B polymorphisms modulate the
      association between phthalate exposure and BC risk.

PMID- 23866027
TI  - Dermoscopy of uncommon skin tumours.

PMID- 23866028
TI  - Ultra-pure platelet isolation from canine whole blood.
AB  - BACKGROUND: Several research applications involving platelets, such as proteomic
      and transcriptomic analysis, require samples with very low numbers of
      contaminating leukocytes, which have considerably higher RNA and protein content
      than platelets. We sought to develop a platelet purification protocol that would
      minimize contamination, involve minimal centrifugation steps, and yield highly
      pure platelet samples derived from low volume whole blood samples from healthy
      dogs. RESULTS: Using an optimized OptiPrep density gradient technique, platelet
      recovery was 51.56% with 99.99% platelet purity and leukocyte contamination of
      100 leukocytes per 108 platelets, on average. Platelet samples were subjected to
      additional purification with CD45-labeled Dynabeads after density barrier
      centrifugation resulting in a 95-fold depletion of residual leukocytes. Platelets
      purified using these methods remained inactivated as assessed by Annexin V and P
      selectin labeling with flow cytometry. CONCLUSIONS: The use of OptiPrep density
      gradient is a quick method for obtaining highly purified platelet samples from
      low volumes of canine whole blood with minimal contamination. Additional
      depletion of residual leukocytes can be achieved using CD45-labeled beads. These
      platelet samples can then be used for many downstream applications that require
      ultra-pure platelet samples such as RNA and protein analysis.

PMID- 23866029
TI  - Complex suicide by self-stabbing with subsequent drowning in the sea.
AB  - The paper presents a unique case of a complex suicide committed by a young man,
      mostly probably triggered by a disappointment in love. The uniqueness of the
      suicide lies in the fact that the victim inflicted several deep stab wounds on
      himself, in the chest and abdomen, while standing partly submerged in the sea
      and, having done so, he dropped and disappeared in the water. The postmortem
      examination showed, apart from deep wounds in the trunk, characteristics of
      drowning that manifested itself in the form of aqueous emphysema of the lungs.
      Suicide was clearly determined on the basis of the circumstances preceding death,
      the location, and arrangement of the trunk wounds and the testimony given by a
      witness of the incident. The circumstances preceding the suicidal act clearly
      suggest an underlying undiagnosed mental disorder. 

PMID- 23866031
TI  - Convergent evolution of morphology and habitat use in the explosive Hawaiian
      fancy case caterpillar radiation.
AB  - Species occurring in unconnected, but similar habitats and under similar
      selection pressures often display strikingly comparable morphology, behaviour and
      life history. On island archipelagos where colonizations and extinctions are
      common, it is often difficult to separate whether similar traits are a result of
      in situ diversification or independent colonization without a phylogeny. Here, we
      use one of Hawaii's most ecologically diverse and explosive endemic species
      radiations, the Hawaiian fancy case caterpillar genus Hyposmocoma, to test
      whether in situ diversification resulted in convergence. Specifically, we examine
      whether similar species utilizing similar microhabitats independently developed
      largely congruent larval case phenotypes in lineages that are in comparable, but
      isolated environments. Larvae of these moths are found on all Hawaiian Islands
      and are characterized by an extraordinary array of ecomorphs and larval case
      morphology. We focus on the 'purse cases', a group that is largely specialized
      for living within rotting wood. Purse cases were considered a monophyletic group,
      because morphological, behavioural and ecological traits appeared to be shared
      among all members. We constructed a phylogeny based on nuclear and mitochondrial
      DNA sequences from 38 Hyposmocoma species, including all 14 purse case species
      and 24 of non-purse case congeners. Divergence time estimation suggests that
      purse case lineages evolved independently within dead wood and developed nearly
      identical case morphology twice: once on the distant Northwest Hawaiian Islands
      between 15.5 and 9 Ma and once on the younger main Hawaiian Islands around 3.0
      Ma. Multiple ecomorphs are usually found on each island, and the ancestral
      ecomorph of Hyposmocoma appears to have lived on tree bark. Unlike most endemic
      Hawaiian radiations that follow a clear stepwise progression of colonization,
      purse case Hyposmocoma do not follow a pattern of colonization from older to
      younger island. We postulate that the diversity of microhabitats and selection
      from parasitism/predation from endemic predators may have shaped case
      architecture in this extraordinary endemic radiation of Hawaiian insects. 

PMID- 23866030
TI  - Double-positive expression of high-mobility group box 1 and vascular endothelial
      growth factor C indicates a poorer prognosis in gastric cancer patients.
AB  - BACKGROUND: Although many studies have indicated that high-mobility group box 1
      protein (HMGB1) is associated with oncogenesis and a worse prognosis, the
      prognostic value of HMGB1 in gastric cancer (GC) remains unclear. In the present
      work, we aimed to evaluate the role of HMGB1 in GC and examined whether aberrant
      expression of both HMGB1 and vascular endothelial growth factor C (VEGF-C)
      increased the malignant potential of GC. METHODS: A total of 166 GC patients and
      32 normal subjects were enrolled. HMGB1 and VEGF-C expression was detected by
      tissue microarrays (TMAs) and immunohistochemical staining. The correlation
      between HMGB1 and VEGF-C expression and their relationships with
      clinicopathological GC variables were examined. Univariate and multivariate
      analyses were performed using the Cox proportional hazard model to predict the
      factors related to the patients' overall survival rates. RESULTS: HMGB1 and VEGF
      C expression were observed in 81 (48.80%) and 88 (53.01%) tumors, respectively,
      significantly higher than the rates among the corresponding controls. In
      addition, HMGB1 and VEGF-C expression were positively correlated (R2 = 0.972).
      HMGB1 expression was also closely associated with tumor size, pT stage, nodal
      status, metastasis status, TNM stage, and poor prognosis. Multivariate survival
      analysis indicated that patients with HMGB1 and VEGF-C coexpression had the worst
      prognoses and survival rates (hazard ratio, 2.78; log rank P<0.001). CONCLUSIONS:
      HMGB1 is commonly expressed in GC. Combined evaluation of HMGB1 and VEGF-C may
      serve as a valuable independent prognostic factor for GC patients.

PMID- 23866032
TI  - Techniques of extracorporeal cytokine removal: a systematic review of human
      studies.
AB  - BACKGROUND AND AIMS: Hypercytokinemia is believed to be harmful and reducing
      cytokine levels is considered beneficial. Extracorporeal blood purification (EBP)
      techniques have been studied for the purpose of cytokine reduction. We aimed to
      study the efficacy of various EBP techniques for cytokine removal as defined by
      technical measures. METHOD: We conducted a systematic search for human clinical
      trials which focused on technical measures of cytokine removal by EBP techniques.
      We identified 41 articles and analyzed cytokine removal according to clearance
      (CL), sieving coefficient (SC), ultrafiltrate (UF) concentration and percentage
      removed. RESULTS: We identified the following techniques for cytokine removal:
      standard hemofiltration, high volume hemofiltration (HVHF), high cut-off (HCO)
      hemofiltration, plasma filtration techniques, and adsorption techniques,
      ultrafiltration (UF) techniques relating to cardiopulmonary bypass (CPB),
      extracorporeal liver support systems and hybrid techniques including combined
      plasma filtration adsorption. Standard filtration techniques and UF techniques
      during CPB were generally poor at removing cytokines (median CL for interleukin 6
      [IL-6]: 1.09 mL/min, TNF-alpha 0.74 mL/min). High cut-off techniques consistently
      offered moderate cytokine removal (median CL for IL-6: 26.5 mL/min, interleukin 1
      receptor antagonist [IL-1RA]: 40.2 mL/min). Plasma filtration and extracorporeal
      liver support appear promising but data are few. Only one paper studied combined
      plasma filtration and adsorption and found low rates of removal. The clinical
      significance of the cytokine removal achieved with more efficacious techniques is
      unknown. CONCLUSION: Human clinical trials indicate that high cut-off
      hemofiltration techniques, and perhaps plasma filtration and extracorporeal liver
      support techniques are likely more efficient in removing cytokines than standard
      techniques.

PMID- 23866033
TI  - Experimental evidence for a cost of resistance to the fungal pathogen,
      Batrachochytrium dendrobatidis, for the palmate newt, Lissotriton helveticus.
AB  - BACKGROUND: Batrachochytrium dendrobatidis (Bd), the causative agent of
      chytridiomycosis, is decimating amphibians worldwide. Unsurprisingly, the
      majority of studies have therefore concentrated on documenting morbidity and
      mortality of susceptible species and projecting population consequences as a
      consequence of this emerging infectious disease. Currently, there is a paucity of
      studies investigating the sub-lethal costs of Bd in apparently asymptomatic
      species, particularly in controlled experimental conditions. Here we report the
      consequences of a single dose of B. dendrobatidis zoospores on captive adult
      palmate newts (Lissotriton helveticus) for morphological and behavioural traits
      that associate with reproductive success. RESULTS: A single exposure to ~2000
      zoospores induced a subclinical Bd infection. One week after inoculation 84% of
      newts tested positive for Bd, and of those, 98% had apparently lost the infection
      by the day 30. However, exposed newts suffered significant mass loss compared
      with control newts, and those experimental newts removing higher levels of Bd
      lost most mass. We found no evidence to suggest that three secondary sexual
      characteristics (areas of dorsal crest and rear foot webbing, and length of tail
      filament) were reduced between experimental versus control newts; in fact, rear
      foot webbing was 26% more expansive at the end of the experiment in exposed
      newts. Finally, compared with unexposed controls, exposure to Bd was associated
      with a 50% earlier initiation of the non-reproductive terrestrial phase.
      CONCLUSIONS: Our results suggest that Bd has measureable, but sub-lethal effects,
      on adult palmate newts, at least under the laboratory conditions presented. We
      conclude that the effects reported are most likely to be mediated through the
      initiation of costly immune responses and/or tissue repair mechanisms. Although
      we found no evidence of hastened secondary sexual trait regression, through
      reducing individual body condition and potentially, breeding season duration, we
      predict that Bd exposure might have negative impacts on populations of palmate
      newts through reducing individual reproductive success and adult recruitment.

PMID- 23866034
TI  - Synergy between enzastaurin doxorubicin in inducing melanoma apoptosis.
AB  - Melanoma is resistant to most standard chemotherapeutics. We analysed the
      combined effect of doxorubicin and enzastaurin on cell death of four melanoma
      cell lines, namely G361, SK-MEL3, A375 and SAN. Enzastaurin IC50 was calculated
      by measure of growth inhibition with MTS assay and corresponded to 2 MUM; the
      half maximal cytotoxicity of doxorubicin was obtained at 3 MUM dose. Evaluation
      of combination index showed synergism (CI > 1) or additive effect (CI = 1) with
      all melanoma cell lines, with enzastaurin doses >=0.6 MUM and doxorubicin doses
      >=1 MUM. Combination of the two drugs resulted in increase in caspase 3 and 8
      activation, in comparison with activation by single agents. Caspase 8 activation
      was impaired by TNFR-1 blocking. Our results show doxorubicin-stimulated
      production of TNFalpha, whereas enzastaurin-stimulated TNFR-1 expression on
      plasma membrane. The effect on TNFR-1 appeared to be mediated by PKCzeta
      inhibition. Taken together, our findings suggest that enzastaurin increases
      doxorubicin-induced apoptosis of melanoma by a mechanism involving, at least in
      part, activation of the TNF-alpha signal. 

PMID- 23866036
TI  - Globalization of the cashmere market and the decline of large mammals in central
      Asia.
AB  - As drivers of terrestrial ecosystems, humans have replaced large carnivores in
      most areas, and human influence not only exerts striking ecological pressures on
      biodiversity at local scales but also has indirect effects in distant corners of
      the world. We suggest that the multibillion dollar cashmere industry creates
      economic motivations that link western fashion preferences for cashmere to land
      use in Central Asia. This penchant for stylish clothing, in turn, encourages
      herders to increase livestock production which affects persistence of over 6
      endangered large mammals in these remote, arid ecosystems. We hypothesized that
      global trade in cashmere has strong negative effects on native large mammals of
      deserts and grassland where cashmere-producing goats are raised. We used time
      series data, ecological snapshots of the biomass of native and domestic
      ungulates, and ecologically and behaviorally based fieldwork to test our
      hypothesis. In Mongolia increases in domestic goat production were associated
      with a 3-fold increase in local profits for herders coexisting with endangered
      saiga (Saiga tatarica).That increasing domestic grazing pressure carries fitness
      consequences was inferred on the basis of an approximately 4-fold difference in
      juvenile recruitment among blue sheep (Pseudois nayaur)in trans-Himalayan India.
      Across 7 study areas in Mongolia, India, and China's Tibetan Plateau, native
      ungulate biomass is now <5% that of domestic species. Such trends suggest
      ecosystem degradation and decreased capacity for the persistence of native
      species, including at least 8 Asian endemic species: saiga, chiru (Pantholops
      hodgsoni), Bactrian camel (Camelus bactrianus), snow leopard(Panthera uncia),
      khulan(Equus hemionus), kiang (E. kiang), takhi (E. przewalski), and wild yak
      (Bos mutus). Our results suggest striking yet indirect and unintended actions
      that link trophic-level effects to markets induced by the trade for cashmere.

PMID- 23866037
TI  - Use of historical logging patterns to identify disproportionately logged
      ecosystems within temperate rainforests of southeastern Alaska.
AB  - The forests of southeastern Alaska remain largely intact and contain a
      substantial proportion of Earth's remaining old-growth temperate rainforest.
      Nonetheless, industrial-scale logging has occurred since the 1950s within a
      relatively narrow range of forest types that has never been quantified at a
      regional scale. We analyzed historical patterns of logging from 1954 through 2004
      and compared the relative rates of change among forest types, landform
      associations, and biogeographic provinces. We found a consistent pattern of
      disproportionate logging at multiple scales, including large-tree stands and
      landscapes with contiguous productive old-growth forests. The highest rates of
      change were among landform associations and biogeographic provinces that
      originally contained the largest concentrations of productive old growth (i.e.,
      timber volume >46.6 m3/ha). Although only 11.9% of productive old-growth forests
      have been logged region wide, large-tree stands have been reduced by at least
      28.1%, karst forests by 37%, and landscapes with the highest volume of contiguous
      old growth by 66.5%. Within some island biogeographic provinces, loss of rare
      forest types may place local viability of species dependent on old growth at risk
      of extirpation. Examination of historical patterns of change among ecological
      forest types can facilitate planning for conservation of biodiversity and
      sustainable use of forest resources.

PMID- 23866038
TI  - Insights for integrated conservation from attitudes of people toward protected
      areas near Hwange National Park, Zimbabwe.
AB  - Increase in human settlements at the edge of protected areas (PAs) is perceived
      as a major threat to conservation of biodiversity. Although it is crucial to
      integrate the interests of surrounding communities into PA management, key
      drivers of changes in local populations and the effects of conservation on local
      livelihoods and perceptions remain poorly understood. We assessed population
      changes from 1990 to 2010 in 9 villages located between 2 PAs with different
      management policies (access to natural resources or not). We conducted semi
      directive interviews at the household level (n =217) to document reasons for
      settlement in the area and villager's attitudes toward the PAs. We examined
      drivers of these attitudes relative to household typology, feelings about
      conservation, and concerns for the future with mixed linear models. Population
      increased by 61% from 2000 to 2010, a period of political and economic crisis in
      Zimbabwe. Forty-seven percent of immigrants were attracted by the area; others
      had been resettled from other villages or were returning to family lands.
      Attitudes toward PAs were generally positive, but immigrants attracted by the
      area and who used resources within the PA with fewer restrictions expressed more
      negative attitudes toward PAs. Household location, losses due to wild animals,
      and restrictions on access to natural resources were the main drivers of this
      negative attitude. Profit-seeking migrants did not expect these constraints and
      were particularly concerned with local overpopulation and access to natural
      resources. To avoid socio-ecological traps near PAs (i.e., unforeseen reduced
      adaptive capacity) integrated conservation should address mismatches between
      management policy and local expectations. This requires accounting for endogenous
      processes, for example, local socio-ecological dynamics and values that shape the
      coexistence between humans and wildlife.

PMID- 23866039
TI  - Critical need for modification of U.S. population policy.

PMID- 23866042
TI  - Pharmacokinetics of an injectable long-acting parenteral formulation of
      doxycycline hyclate in pigs.
AB  - Based on its ideal PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant
      antibacterial, is ideally expected to achieve sustained plasma drug
      concentrations at or slightly above the MIC level for as long as possible between
      dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce
      a 10% long-acting injectable preparation (DOX-h-LA) and its serum concentrations
      vs. time profile investigated after its injection to pigs in the pericaudal s.c.
      by parallel design. Results were compared with the forced oral bolus dose and
      i.v. pharmacokinetics of DOX-h. For this study, 12 recently weaned pigs per group
      were included in this trial, and a dose of 20 mg/kg was injected in all cases.
      DOX-h-LA showed the greatest values for bioavailability (115.38%); maximum serum
      concentration (Cmax) value was 1.5 +/- 0.2 with a time to reach Cmax of 3.41 +/-
      0.04 h and an elimination rate constant of 70.93 +/- 0.87( ) h. Considering
      minimum effective serum concentration of 0.5 MUg/mL, a dose interval of at least
      5 days can be achieved for DOX-h-LA, whereas p.o. and i.v. dosing of DOX-h may
      only last 11 and 15 h, respectively. Pigs were slaughtered on day 30 after this
      trial, and no visible remnants of the preparation were detected neither fibrosis
      was observed after a thorough macroscopic and histopathological analysis.

PMID- 23866043
TI  - Phytochemicals and biological studies of plants in genus Hedysarum.
AB  - In China, several species (Hedysarum polybotrys Hand.-Mazz., Hedysarum
      limprichtii Hlbr., Hedysarum vicioider Turcz. var. Taipeicum Hand.-Mazz. Liu,
      Hedysarum smithianum, et al.) of genus Hedysarum have a long history of use in
      traditional Chinese medicine (TCM). In TCM, these plants are used to increase the
      energy of the body. To date, 155 compounds, including flavonoids, triterpenes,
      coumarins, lignanoids, nitrogen compounds, sterols, carbohydrates, fatty
      compounds, and benzofuran, have been isolated from plants of the genus Hedysarum.
      Various chemical constituents contribute to the antioxidant, anti-tumor, anti
      aging, anti-diabetic, and anti-hypertensive properties of these plants. Hedysarum
      species are used to treat infestation with gastrointestinal nematodes and may
      support the immune system and peripheral nervous system. In the present review,
      we summarize the research on the phytochemistry and pharmacology of Hedysarum
      species, which will be useful for better utilization of these important species
      in TCM. 

PMID- 23866044
TI  - Community experiences and perceptions of reproductive health vouchers in Kenya.
AB  - BACKGROUND: Research on demand-side health care financing approaches such as
      output-based aid (OBA) programs have focused on evaluating the role of the
      programs improving such outcomes as utilization of services and quality of
      services with limited focus on the experiences and perceptions of the target
      communities. This paper examines community members' views of the output-based aid
      voucher program in Kenya. METHODS: A household survey was conducted in 2010 among
      1,336 women aged 15-49 years living in the catchment areas of contracted health
      facilities in three districts participating in the voucher program (Kisumu,
      Kiambu and Kitui). Twenty seven focus group discussions were conducted with
      voucher users, non-users, opinion leaders and voucher distributors in the three
      districts as well as in Nairobi. Analysis of the quantitative data involved
      frequency distributions and cross-tabulations. Qualitative data were transcribed
      and analyzed by adopting framework analysis and further triangulation of themes
      across respondents. RESULTS: Majority (84%) of survey respondents had heard about
      the safe motherhood voucher compared to 24% and 1% that had heard about the
      family planning and gender-based violence recovery services (GBVRS) vouchers
      respectively. Similarly, 20% of the respondents had used the safe motherhood
      voucher compared to 2% for family planning and none for the GBVRS vouchers. From
      the community members' perspectives, the voucher program is associated with
      improvements in access to health services for poor women, improved quality of
      care, and empowerment of women to make health care decisions. However, community
      members cited difficulties in accessing some accredited health facilities,
      limitations with the system of selling vouchers, lack of male involvement in
      women's reproductive health issues, and poor understanding of the benefits
      associated with purchasing the voucher. CONCLUSION: The findings of this paper
      showed that the voucher program in Kenya is viewed by the community members as a
      feasible system for increasing service utilization, improving quality of care,
      and reducing financial barriers to accessing reproductive health services.
      However, the techniques of program execution such as proper information and
      availability of the distributors as well as local attitudes influence whether
      vouchers are purchased and used.

PMID- 23866046
TI  - Sperm morphometry: a tool for detecting biophysical changes associated with
      viability in cryopreserved bovine spermatozoa.
AB  - The aim of this study was to determine whether computerised sperm head
      morphometric analysis can be used as a diagnostic tool for detecting biophysical
      changes associated with sperm viability in frozen-thawed bovine spermatozoa.
      Ejaculates from five bulls (4 ejaculates/bull) were pooled and processed for
      computerised morphometric analysis, and SYBR-14 green/ethidium homodimer-1
      fluorescence-based live/dead viability assay was used simultaneously to confirm
      the viability index of frozen-thawed spermatozoa. Sperm samples were assigned to
      three experimental groups. The first group was enriched in live spermatozoa
      (after a double Percoll selection), the second group was enriched in dead
      spermatozoa (after a refreeze-thaw procedure), and the last group was a 50 : 50
      pool of live/dead spermatozoa (from first and second group samples). There were
      significant differences (P < 0.001) related to sperm morphometric dimensional
      parameters among the three groups analysed, being the lowest overall sperm head
      dimension found in the second (dead spermatozoa) group. In conclusion, sperm head
      morphometry can be used as a potential diagnostic tool for detecting biophysical
      changes associated with sperm viability in frozen-thawed bovine spermatozoa.

PMID- 23866045
TI  - A cytokine-controlled mechanism for integrated regulation of T-lymphocyte
      motility, adhesion and activation.
AB  - The co-ordination of T-cell motility, adhesion and activation remains poorly
      understood. It is also unclear how these functions are co-ordinated with external
      stimuli. Here we unveil a series of molecular interactions in cis at the surface
      of T lymphocytes with potent effects on motility and adhesion in these cells, and
      communicating with proliferative responses. These interactions were controlled by
      the signature cytokines of T helper subsets interleukin-2 (IL-2) and IL-4. Low
      density lipoprotein receptor-related protein 1 (LRP1) was found to play a key
      role for T-cell motility by promoting development of polarized cell shape and
      cell movement. Endogenous thrombospondin-1 (TSP-1) enhanced cell surface
      expression of LRP1 through CD47. Cell surface expressed LRP1 induced motility and
      processing of TSP-1 while inhibiting adhesion to intercellular adhesion molecule
      1 and fibronectin. Interleukin-2, but not IL-4, stimulated synthesis of TSP-1 and
      motility through TSP-1 and LRP1. Stimulation of the T-cell receptor (TCR)/CD3
      complex inhibited TSP-1 expression. Inhibitor studies indicated that LRP1
      regulated TSP-1 expression and promoted motility through JAK signalling. This
      LRP1-mediated motogenic signalling was connected to CD47/Gi protein signalling
      and IL-2-induced signalling through TSP-1. The motogenic TSP-1/LRP1 mechanism
      antagonized TCR/CD3-induced T-cell proliferation. These results indicate that
      LRP1 in collaboration with TSP-1 directs a counter-adhesive and counter
      proliferative motogenic cascade. T cells seem programmed to prioritize movement
      before adhesion through this cascade. In conclusion, vital decision-making in T
      lymphocytes regulating motility, adhesive interactions and proliferation, are
      integrated through a molecular mechanism connecting different cell surface
      receptors and their signalling pathways. 

PMID- 23866047
TI  - Brain H2A.Z: the long and the short.
AB  - The role of histone variants and their specific post-translational modifications
      (PTMs) in the epigenetic regulation of gene expression is still poorly
      understood. A paper published by Simonet and colleagues in Epigenetics and
      Chromatin describes a new H2A.Z subtype that is specific for brain and pituitary
      in the carp and provides additional information about the functional epigenetic
      complexity of the PTMs associated with histone H2A.Z.

PMID- 23866048
TI  - Clinical impact of diagnostic imaging discrepancy by radiology trainees in an
      urban teaching hospital emergency department.
AB  - BACKGROUND: To characterize clinically significant diagnostic imaging (DI)
      discrepancies by radiology trainees and the impact on emergency department (ED)
      patients. METHODS: Consecutive case series methodology over a 6-month period in
      an urban, tertiary care teaching hospital. Emergency physicians (EPs) were
      recruited to flag discrepant DI interpretations by radiology trainees that the EP
      deemed clinically significant. Cases were characterized using chart review and EP
      interview. RESULTS: Twenty-eight discrepant reports were identified (representing
      0.1% of 18,185 images interpreted). The mean time between provisional discrepant
      diagnosis (PDDx) and revised diagnosis (RDx) by attending radiology staff was 8.6
      h (median 4.8 h, range 1.1-48.4), and 67.9% (n = 19) of the patients had left the
      ED by time of notification. The most frequently reported PDDx was CT abd/pelvis
      (32.1%, n = 9) and CT head (28.6%, n = 8). The impact of RDx was deemed major in
      57.1% (n = 16) for reasons including altered admitting status (32.1%, n = 9),
      immediate subspecialty referral (n = 16, 57.1%), impact on management (25%, n =
      7), and surgical management (21.4%, n = 6). EPs reported likely perceived impact
      of PDDx as resulting in increased pain (17. 9%, n = 5), morbidity (10.7%, n = 3),
      and prolonged hospitalization (25%, n = 7), but not altered long-term outcome or
      mortality. CONCLUSIONS: Relatively few clinically important discrepant reads were
      reported. Revised diagnosis (RDx) was associated with major clinical impact in
      57.1% of reports, but few patients experienced increased morbidity, and none
      increased mortality. The importance of expedient communication of discrepant
      reports by staff radiologists is stressed, as is EP verification of patient
      contact information prior to discharge.

PMID- 23866049
TI  - Particulate air pollution and health inequalities: a Europe-wide ecological
      analysis.
AB  - BACKGROUND: Environmental disparities may underlie the unequal distribution of
      health across socioeconomic groups. However, this assertion has not been tested
      across a range of countries: an important knowledge gap for a transboundary
      health issue such as air pollution. We consider whether populations of low-income
      European regions were a) exposed to disproportionately high levels of particulate
      air pollution (PM10) and/or b) disproportionately susceptible to pollution
      related mortality effects. METHODS: Europe-wide gridded PM10 and population
      distribution data were used to calculate population-weighted average PM10
      concentrations for 268 sub-national regions (NUTS level 2 regions) for the period
      2004-2008. The data were mapped, and patterning by mean household income was
      assessed statistically. Ordinary least squares regression was used to model the
      association between PM10 and cause-specific mortality, after adjusting for
      regional-level household income and smoking rates. RESULTS: Air quality improved
      for most regions between 2004 and 2008, although large differences between
      Eastern and Western regions persisted. Across Europe, PM10 was correlated with
      low household income but this association primarily reflected East-West
      inequalities and was not found when Eastern or Western Europe regions were
      considered separately. Notably, some of the most polluted regions in Western
      Europe were also among the richest. PM10 was more strongly associated with
      plausibly-related mortality outcomes in Eastern than Western Europe, presumably
      because of higher ambient concentrations. Populations of lower-income regions
      appeared more susceptible to the effects of PM10, but only for circulatory
      disease mortality in Eastern Europe and male respiratory mortality in Western
      Europe. CONCLUSIONS: Income-related inequalities in exposure to ambient PM10 may
      contribute to Europe-wide mortality inequalities, and to those in Eastern but not
      Western European regions. We found some evidence that lower-income regions were
      more susceptible to the health effects of PM10.

PMID- 23866050
TI  - Insulin resistance is significantly associated with the metabolic syndrome, but
      not with sonographically proven peripheral arterial disease.
AB  - OBJECTIVE: Insulin resistance (IR) is the key feature of the metabolic syndrome
      (MetS); its association with peripheral arterial disease (PAD) is unclear. We
      hypothesized that IR is associated with both the MetS and sonographically proven
      PAD. METHODS: IR was determined by the Homeostasis Model Assessment (HOMA) index
      in 214 patients with sonographically proven PAD as well as in 197 controls, who
      did not have a history of PAD and in whom coronary artery disease was ruled out
      angiographically; the MetS was defined according to NCEP-ATPIII criteria.
      RESULTS: HOMA IR scores were significantly higher in MetS patients than in
      subjects without the MetS (5.9 +/- 6.2 vs. 2.9 +/- 3.9; p <0.001). However, HOMA
      IR did not differ significantly between patients with PAD and controls (4.2 +/-
      5.4 vs. 3.3 +/- 4.3; p = 0.124). When both, the presence of MetS and of PAD were
      considered, HOMA IR was significantly higher in patients with the MetS both among
      those with PAD (6.1 +/- 5.7 vs. 3.6 +/- 5.2; p<0.001) and among controls (5.8 +/-
      6.8 vs. 2.3 +/- 1.8; p <0.001), whereas it did not differ significantly between
      patients with PAD and controls among patients with the MetS (5.8 +/- 6.8 vs. 6.1
      +/- 5.7; p = 0.587) nor among those without the MetS (2.3 +/- 1.8 vs. 3.6 +/-
      5.2; p = 0.165). Similar results were obtained with the International Diabetes
      Federation definition of the MetS. CONCLUSION: IR is significantly associated
      with the MetS but not with sonographically proven PAD.

PMID- 23866051
TI  - Functional characterization of Staphylococcus epidermidis IcaB, a de-N-acetylase
      important for biofilm formation.
AB  - A polymer of partially de-N-acetylated beta-1,6-linked N-acetylglucosamine
      (dPNAG), also known as the polysaccharide intercellular adhesin (PIA), is an
      important component of many bacterial biofilm matrices. In Staphyloccocus
      epidermidis, the poly-N-acetylglucosamine polymer is partially de-N-acetylated by
      the extracellular protein IcaB. To understand the mechanism of action of IcaB,
      the enzyme was overexpressed and purified. IcaB demonstrates metal-dependent de-N
      acetylase activity on beta-1,6-linked N-acetylglucosamine oligomers with a broad
      preference for divalent metals. Steady-state kinetic analysis reveals the low
      catalytic efficiency (pentasaccharide kcat/KM 0.03 M(-1) s(-1)) of the enzyme
      toward the oligomeric substrates. While IcaB displays similar rates of de-N
      acetylation with tri- through hexasaccharide PNAG oligomers, position specific de
      N-acetylation was only observed with penta- and hexasaccharides. The enzyme
      preferentially de-N-acetylates the second residue from the reducing terminus in
      the pentasaccharide and second and third residues from the reducing terminus in
      the hexasaccharide. The data described here represent an important step toward a
      detailed understanding of dPNAG biosynthesis in S. epidermidis, an important
      nosocomial pathogen, as well as in other Gram-positive bacteria. The low
      catalytic activity of IcaB is consistent with reports of other enzymes which act
      on biofilm-related polysaccharides, and this emerging trend may indicate a common
      feature among this group of polysaccharide processing enzymes. 

PMID- 23866052
TI  - A new analogy for the effects of ambient particles on health.

PMID- 23866053
TI  - Chronotypes of bipolar patients in remission: validation of the French version of
      the circadian type inventory in the FACE-BD sample.
AB  - Circadian rhythm disturbances have been associated with bipolar disorder (BD)
      during both the mood episodes and the periods of remission. Circadian phase
      preferences for the evening have been reported for remitted patients, whereas the
      amplitude and stability of their rhythms have never been assessed using
      questionnaires. The primary aim of our study was the validation of a French
      version of the Circadian Type Inventory (CTI), whereas its secondary aim was the
      comparison between remitted patients with BD and healthy controls for rhythm
      stability and amplitude and for phase preference. For this purpose, we used the
      CTI and the Composite Scale of Morningness (CSM) that assesses phase preference
      ("morning" or "evening" type). First, we report here on the validation of the
      French version of the 11-item Circadian Type Inventory in a sample of 140
      remitted patients with BD and 156 healthy controls. Principal components analysis
      revealed a two-factor structure (FR: flexibility/rigidity scale corresponding to
      rhythm stability; LV: languid/vigorous scale corresponding to rhythm amplitude)
      explaining 52% of the variance in the control group and 47% in the bipolar group.
      Cronbach's alpha was 0.75 for FR and 0.73 for LV. The test-retest reliability was
      0.74 for FR and 0.86 for LV (3 wks) and 0.62 for FR and 0.72 for LV (6 mos). LV
      and FR scores correlated with the Composite Scale of Morningness score (p <
      0.00001 and p = 0.0002, respectively). Second, as compared with controls,
      patients with BD were more languid (p < 0.00001) and showed an evening preference
      (p = 0.0003), but they did not differ from the controls with regard to
      flexibility/rigidity. The French version of the CTI appeared to have satisfactory
      psychometrics characteristics. Bipolar patients exhibited not only abnormalities
      in phase preference but also in amplitude as measured by languidity. Since
      circadian rhythm dysfunction has been shown to predict poor functioning and mood
      relapses in interepisodic patients with BD, this tool would appear to be a
      promising, easy-to-use, measure of the amplitude and flexibility of circadian
      rhythms that could enrich the arsenal of assessments used in clinical settings.

PMID- 23866054
TI  - Circadian Disruption: comparing humans with mice.
AB  - Disruption of the 24-h light-dark cycle has been implicated as an endocrine
      disruptor and linked to increased morbidity and mortality in animal studies.
      Previously reported measurements of circadian disruption in day-shift and
      rotating-shift nurses were compared with new mouse data where the light-dark
      patterns simulated shiftwork. Phasor magnitudes, a measure of circadian
      entrainment, were shown to be similar for humans and for mice when exposed to
      similar patterns of light and dark. Phasor analyses may be a useful method for
      quantitatively bridging ecological measurements of circadian disruption in human
      with parametric studies of health outcomes in a mouse model. 

PMID- 23866055
TI  - Evaluation of immune and stress status in harbour porpoises (Phocoena phocoena):
      can hormones and mRNA expression levels serve as indicators to assess stress?
AB  - BACKGROUND: The harbour porpoise is exposed to increasing pressure caused by
      anthropogenic activities in its marine environment. Numerous offshore wind farms
      are planned or under construction in the North and Baltic Seas, which will
      increase underwater noise during both construction and operation. A better
      understanding of how anthropogenic impacts affect the behaviour, health,
      endocrinology, immunology and physiology of the animals is thus needed. The
      present study compares levels of stress hormones and mRNA expression of cytokines
      and acute-phase proteins in blood samples of harbour porpoises exposed to
      different levels of stress during handling, in rehabilitation or permanent human
      care.Free-ranging harbour porpoises, incidentally caught in pound nets in
      Denmark, were compared to harbour porpoises in rehabilitation at SOS Dolfijn in
      Harderwijk, the Netherlands, and individuals permanently kept in human care in
      the Dolfinarium Harderwijk and Fjord & Belt Kerteminde, Denmark. Blood samples
      were investigated for catecholamines, adrenaline, noradrenaline and dopamine, as
      well as for adrenocorticotropic hormone (ACTH), cortisol, metanephrine and
      normetanephrine. mRNA expression levels of relevant cell mediators (cytokines IL
      10 and TNFalpha, acute-phase proteins haptoglobin and C-reactive protein and the
      heat shock protein HSP70) were measured using real-time PCR. RESULTS: Biomarker
      expression levels varied between free-ranging animals and porpoises in human
      care. Hormone and cytokine ranges showed correlations to each other and to the
      health status of investigated harbour porpoises. Hormone concentrations were
      higher in free-ranging harbour porpoises than in animals in human care.
      Adrenaline can be used as a parameter for the initial reaction to acute stress
      situations; noradrenaline, dopamine, ACTH and cortisol are more likely indicators
      for the following minutes of acute stress. There is evidence for different
      correlations between production of normetanephrine, metanephrine, cortisol and
      the expression of IL-10, HSP70 and haptoglobin. CONCLUSIONS: The expression
      patterns of the selected molecular biomarkers of the immune system are promising
      to reflect the health and immune status of the harbour porpoise under different
      levels of stress.

PMID- 23866056
TI  - Formulae for estimating skeletal height in modern South-East Asians.
AB  - Estimating stature in human skeletal remains of Asian ancestry is problematic for
      forensic anthropologists due to the paucity and uncertain suitability of
      regression formulae. To address this issue, our study analyzed 64 individuals
      from a modern skeletal collection of South-East Asian origin and developed
      population-specific ordinary least squares regression formulae to estimate
      skeletal height from each of the long bones of the upper and lower limbs, as well
      as from trunk length. Results indicate that the most accurate estimates of
      skeletal height from a single bone (as measured by standard error of the estimate
      SEE) are from tibial length in males (SEE = 2.40 cm) and from humeral length in
      females (SEE = 2.59 cm), followed by femoral length (SEE = 2.84 cm). When
      multiple elements are considered, the combination of femoral and tibial length
      yields the best estimates in both sexes as well as combined sex samples (male SEE
      = 2.40 cm; female SEE = 2.77 cm; combined sex SEE = 2.54 cm). 

PMID- 23866057
TI  - Noninvasive lipoma size reduction using high-intensity focused ultrasound.
AB  - BACKGROUND: Lipomas are common benign mesenchymal tumors commonly removed using
      excision, but in certain cases, surgery is undesirable or ineffective. High
      intensity focused ultrasound (HIFU) offers a noninvasive tumor ablation tool
      increasingly used in the clinic. OBJECTIVE: To evaluate the efficacy and safety
      of a noninvasive lipoma size reduction technology using HIFU. MATERIALS &
      METHODS: Twelve lipomas in nine patients were treated. Patients underwent four
      treatment sessions with a 3-week interval between treatments. Blood and urine
      tests and tolerability based on a standard visual analogue scale (VAS) were used
      to monitor patients for adverse effects. Lipoma volume was determined by
      measuring width and length (manually) and depth (ultrasonically). RESULTS: The
      range of lipoma size was 2.7-169.4 cm3 before treatment and 0.2-119.8 cm3 after
      treatment. Mean volume reduction was 58.1 +/- 22.8%. When palpated, the lipomas
      felt much softer than before treatment. The average VAS score was 4.1 +/- 2.4. No
      significant adverse effects were noted. CONCLUSION: The treatment was shown to be
      effective in noninvasively reducing lipoma size. The average volume reduction was
      substantial and statistically significant. The treatment was safe and well
      tolerated. HIFU may be an alternative treatment modality in cases of lipoma.

PMID- 23866058
TI  - Generating melanocytes from human pluripotent stem cells.
AB  - Coverage on: Mica, Y., Lee, G., Chambers, S. M., Tomishima, M. J., and Studer, L.
      (2013). Modeling Neural Crest Induction, Melanocyte Specification, and Disease
      Related Pigmentation Defects in hESCs and Patient-Specific iPSCS. Cell Reports 3,
      1140-1152. Epidermal melanocytes are pigment-producing cells derived from the
      neural crest (NC), a transient embryonic stem cell population that emerges from
      the dorsal margin of the neural plate in vertebrate embryos. The generation of
      melanocytes encompasses several intricate cellular processes including fate
      specification, proliferation, migration, and differentiation. Aberrant melanocyte
      development and homeostasis is at the onset of many pigmentary disorders, such as
      albinism, piebaldism, vitiligo, hyperplasia, and melanoma. Therefore,
      understanding human melanocytic development and disease is crucial. To this end,
      the establishment of methods that facilitate the study of patient-specific
      melanocyte biology and disease modeling is important. This article is protected
      by copyright. All rights reserved.

PMID- 23866059
TI  - Green colour as a novel dermoscopic finding in the diagnosis of haemosiderotic
      dermatofibroma.

PMID- 23866060
TI  - Prognostic analysis of esophageal cancer in elderly patients: metastatic lymph
      node ratio versus 2010 AJCC classification by lymph nodes.
AB  - BACKGROUND: Recent studies have proposed a new prognostic factor (metastatic
      lymph node ratio, or MLNR) for patients with esophageal cancer (EC). However, to
      the best of our knowledge, there have been no studies conducted to date regarding
      MLNR in elderly patients. The aim of this study was to determine the prognostic
      value of MLNR staging compared with the 2010 American Joint Committee on Cancer
      (AJCC) N staging in elderly patients with EC. METHODS: From January 2001 to
      December 2009, a retrospective analysis of 132 consecutive patients older than 70
      years of age with esophageal squamous cell carcinoma (ESCC) was conducted.
      Prognostic factors for disease-specific survival were analyzed. Receiver
      operating characteristic curves were also plotted to verify the accuracy of MLNR
      staging and N staging for survival prediction. RESULTS: The disease-specific
      survival rates of N0, N1, N2 and N3 patients according to the AJCC Cancer Staging
      Manual Seventh Edition N staging were 65.5%, 42.9%, 22.2% and 0, respectively (N0
      vs N1, P = 0.017; N1 vsN2, = 0.050; N2 vs N3, P < 0.001). The disease-specific
      survival rates of MLNR0, MLNR1, MLNR2 and MLNR3 patients were 65.5%, 45.0%, 21.1%
      and 0, respectively (MLNR0 vsMLNR1, P = 0.026; MLNR1 vs MLNR2, P = 0.033; MLNR2
      vs MLNR3, P = 0.015). The areas under the curve were 0.731 for the 2010 AJCC N
      staging and 0.737 for the MLNR staging. CONCLUSION: MLNR is an independent
      predictor of survival in elderly patients with ESCC. MLNR staging predicts
      survival after EC similarly to the 2010 AJCC N classifications and should be
      considered an alternative to current N staging.

PMID- 23866061
TI  - Impact of initial treatment outcome on long-term costs of depression: a 3-year
      nationwide follow-up study in Taiwan.
AB  - BACKGROUND: The impact of initial treatment outcome on long-term healthcare costs
      in depression remains to be determined. We aimed to identify demographic and
      clinical characteristics associated with initial treatment outcomes and to test
      whether and how these outcomes influence total healthcare costs over the
      subsequent 3 years. METHOD: In this secondary analysis of a large healthcare
      database, a national cohort of adult patients (n = 126,471) who received
      antidepressant treatment for depression was identified and factors associated
      with initial outcomes were examined. Potential predictors of total healthcare
      costs in the subsequent years were assessed using generalized linear modeling,
      with a particular focus on initial outcome status after antidepressant treatment
      and co-morbidities. RESULTS: Depression type and co-morbid painful physical
      symptoms (PPS) or mental illnesses were found to be associated with initial
      outcome status. Having sustained treatment-free status after initial treatment
      was shown to be associated with a 22-33% reduction in total healthcare costs in
      the second and third years (compared to those with late recontacts). Although the
      presence of co-morbid PPS was associated with higher healthcare costs, having
      certain co-morbid anxiety disorders was associated with lower costs over the 3
      years. CONCLUSIONS: Initial outcome status after antidepressant treatment has a
      sustained impact on individuals' total healthcare costs over the following 3
      years. Future efforts to improve initial treatment outcome of depression are
      warranted.

PMID- 23866062
TI  - The overall health and risk factor profile of Australian Aboriginal and Torres
      Strait Islander participants from the 45 and up study.
AB  - BACKGROUND: Despite large disparities in health outcomes between Aboriginal and
      non-Aboriginal Australians, detailed evidence on the health and lifestyle
      characteristics of older Aboriginal Australians is lacking. The aim of this study
      is to quantify socio-demographic and health risk factors and mental and physical
      health status among Aboriginal participants from the 45 and Up Study and to
      compare these with non-Aboriginal participants from the study. METHODS: The 45
      and Up Study is a large-scale study of individuals aged 45 years and older from
      the general population of New South Wales, Australia responding to a baseline
      questionnaire distributed from 2006-2008. Odds ratios (OR) and 95% confidence
      intervals (CI) of self-reported responses from the baseline questionnaire for
      Aboriginal versus non-Aboriginal participants relating to socio-demographic
      factors, health risk factors, current and past medical and surgical history,
      physical disability, functional health limitations and levels of current
      psychological distress were calculated using unconditional logistic regression,
      with adjustments for age and sex. RESULTS: Overall, 1939 of 266,661 45 and Up
      Study participants examined in this study identified as Aboriginal and/or Torres
      Strait Islander (0.7%). Compared to non-Aboriginal participants, Aboriginal
      participants were significantly more likely to be: younger (mean age 58 versus 63
      years); without formal educational qualifications (age- and sex- adjusted OR=6.2,
      95% CI 5.3-7.3); of unemployed (3.7, 2.9-4.6) or disabled (4.6, 3.9-5.3) work
      status; and with a household income< $20,000/year versus >=$70,000/year (5.8, 5.0
      6.9). Following additional adjustment for income and education, Aboriginal
      participants were significantly more likely than non-Aboriginal participants to:
      be current smokers (2.4, 2.0-2.8), be obese (2.1, 1.8-2.5), have ever been
      diagnosed with certain medical conditions (especially: diabetes [2.1, 1.8-2.4];
      depression [1.6, 1.4-1.8] and stroke [1.8, 1.4-2.3]), have care-giving
      responsibilities (1.8, 1.5-2.2); have a major physical disability (2.6, 2.2-3.1);
      have severe physical functional limitation (2.9, 2.4-3.4) and have very high
      levels of psychological distress (2.4, 2.0-3.0). CONCLUSIONS: Aboriginal
      participants from the 45 and Up Study experience greater levels of disadvantage
      and have greater health needs (including physical disability and psychological
      distress) compared to non-Aboriginal participants. The study highlights the need
      to address the social determinants of health in Australia and to provide
      appropriate mental health services and disability support for older Aboriginal
      people.

PMID- 23866063
TI  - Aromatase and glycosyl transferase inhibiting acridone alkaloids from fruits of
      Cameroonian Zanthoxylum species.
AB  - BACKGROUND: Zanthoxylum zanthoxyloides and Z. leprieurii fruits are commonly used
      in traditional system of medicine for diarrhea, pain, wound healing, etc. in
      Cameroon, Africa. Z. leprieurii fruits have been chemically studied for its
      bioactive compounds whereas the investigation on Z. zanthoxyloides fruits is
      lacking. RESULTS: After a detailed chemical analysis of the fruits of Z.
      leprieurii and Z. zanthoxyloides, a series of new acridone alkaloids, namely, 3
      hydroxy-1,5,6-trimethoxy-9-acridone (1), 1,6-dihydroxy-3-methoxy-9-acridone (2),
      3,4,5,7-tetrahydroxy-1-methoxy-10-methyl-9-acridone (3), 4-methoxyzanthacridone
      (8), 4-hydroxyzanthacridone (9), 4-hydroxyzanthacridone oxide (2,4') (10) have
      been isolated. The known acridones which have been characterized are,
      helebelicine A (4), 1-hydroxy-3-methoxy-10-methyl-9-acridone (5), 1,3-dihydroxy-4
      methoxy-10-methyl-9-acridone (6) and tegerrardin A (7). The in vitro
      antibacterial and cytotoxic screening of these acridones reveal that compound 3
      has a moderate antibacterial activity (MIC 125 MUg/mL) against Micrococcus luteus
      and Pseudomonas aeruginosa while compound 1 shows a moderate cytotoxic effect
      (IC50 of 86 MUM) against WRL-68 (liver cancer cell line). Furthermore, the
      molecular modeling of these acridones predicted the structural basis for their
      mode of action and binding affinity for aromatase, quinone reductase and WAAG, a
      glycosyltransferase involved in bacterial lipopolysaccharide synthesis.
      Computational approaches, quantitative SAR and modeling studies predicted that
      acridones 1, 2, 3, 4, 9 and 10 were the inhibitors of glycosyltransferase while
      1, 8, 9 and 10, the inhibitors of aromatase. CONCLUSIONS: A total of 10 acridones
      have been isolated out of which 6 are new (1, 2, 3, 8, 9 and 10). Alkaloids 8, 9
      and 10, having novel tetracyclic acridone structure with new carbon skeleton,
      have now been named as zanthacridone. The quantitative SAR and molecular modeling
      studies suggested that the compounds 1, 9 and 10 are inhibitors of both aromatase
      and glycosyltransferase.

PMID- 23866064
TI  - Perceived parental rearing behaviours, responsibility attitudes and life events
      as predictors of obsessive compulsive symptomatology: test of a cognitive model.
AB  - BACKGROUND: It is important to investigate the role of cognitive, developmental
      and environmental factors in the development and maintenance of Obsessive
      Compulsive Symptomatology (OCS). AIMS: The main objective of this study was to
      examine the vulnerability factors of OCS in a non-clinical sample. On the basis
      of Salkovskis' cognitive model of OCD, the study aimed to investigate the role of
      perceived parental rearing behaviours, responsibility attitudes, and life events
      in predicting OCS. Furthermore, the mediator role of responsibility attitudes in
      the relationship between perceived parental rearing behaviours and OCS was
      examined. Finally, the specificity of these variables to OCS was evaluated by
      examining the relationship of the same variables with depression and trait
      anxiety. METHOD: A total of 300 university students (M = 19.55+/-1.79) were
      administered the Padua Inventory-Washington State University Revision,
      Responsibility Attitudes Scale, s-EMBU (My memories of upbringing), Life Events
      Inventory for University Students, Beck Depression Inventory, and State-Trait
      Anxiety Inventory-Trait Form. RESULTS: Regression analysis revealed that
      perceived mother overprotection, responsibility attitudes and life events
      significantly predicted OCS. Furthermore, responsibility attitudes mediated the
      relationship between perceived mother overprotection and OCS. The predictive role
      of perceived mother overprotection and the mediator role responsibility attitudes
      were OCS specific. CONCLUSIONS: The findings of the present study supported that
      perceived mother over-protection as a developmental vulnerability factor
      significantly contributed to the explanation of a cognitive vulnerability factor
      (namely responsibility attitudes), and perceived maternal overprotection had its
      predictive role for OCS through responsibility attitudes.

PMID- 23866065
TI  - Metabolic survey of defense responses to a compatible hemibiotroph, Phytophthora
      parasitica var. nicotianae, in ethylene signaling-impaired tobacco.
AB  - Reactive oxygen species (ROS) and ethylene play an important role in determining
      the resistance or susceptibility of plants to pathogen attack. A previous study
      of the response of tobacco cultivar ( Nicotiana tabacum L. cv. Wisconsin 38) to a
      compatible hemibiotroph, Phytophthora parasitica var. nicotianae (Ppn) showed
      that biphasic bursts of ROS and ethylene are positively associated with disease
      severity. The levels of ethylene and ROS might influence the susceptibility of
      plants to pathogens, with changing levels of metabolite related to disease
      resistance or susceptibility. In this study, to obtain more detailed information
      on the interaction of ROS and ethylene signaling related to resistance and/or
      susceptibility of plants to pathogen, Ppn-induced metabolic profiles from wild
      type (WT) and ethylene signaling-impaired transgenic plants that expressed Ein3
      antisense (Ein3-AS) were compared using ultraperformance liquid chromatography
      quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Nonredundant mass
      ions (576 in ESI+ mode and 336 in ESI- mode) were selected, and 56 mass ions were
      identified on the basis of their accurate mass ions and MS/MS spectra. Two-way
      hierarchical clustering analysis of the selected mass ions revealed that nicotine
      and phenylpropanoid-polyamine conjugates, such as caffeoyl-dihydrocaffeoyl
      spermidine, dicaffeoyl-spermidine, caffeoyl-feruloyl-spermidine, and two
      bis(dihydrocaffeoyl)-spermine isomers, and their intermediates, such as arginine
      and putrecine, were present at lower levels in Ein3-AS transgenic plants during
      Ppn interaction than in WT, whereas galactolipid and oxidized free fatty acid
      levels were higher in Ein3-AS transgenic plants. Taken together, these results
      reveal a function for ethylene signaling in tobacco defense responses during Ppn
      interaction. 

PMID- 23866067
TI  - Cancer history, bandemia, and serum creatinine are independent mortality
      predictors in patients with infection-precipitated hyperglycemic crises.
AB  - BACKGROUND: Infection is the most common precipitating factor and cause of death
      in patients with hyperglycemic crises. Treating infection-precipitated
      hyperglycemic crises includes using empiric antibiotics early; correcting
      dehydration, hyperglycemia, and electrolyte imbalances; and frequent monitoring.
      Intensive care unit admission, broad-spectrum antibiotics, and even novel therapy
      for infection may be beneficial for patients with a high risk of mortality.
      However, these management options are costly and not beneficial for every
      patient. Selecting high-risk patients who would most likely benefit is more
      appropriate. We investigated the independent mortality predictors of patients
      with infection-precipitated hyperglycemic crises to facilitate clinical decision
      making. METHODS: This study was conducted in a university-affiliated medical
      center. Consecutive adult patients (> 18 years old) visiting the Emergency
      Department between January 2004 and December 2010 were enrolled when they met the
      criteria of an infection-precipitated hyperglycemic crisis. Thirty-day mortality
      was the primary endpoint. RESULTS: One hundred forty-two patients were enrolled.
      The infection source did not predict mortality. The presenting variables that
      were independently associated with 30-day mortality in a multiple logistic
      regression model were cancer history (odds ratio [OR], 7.4; 95% confidence
      interval [CI], 2.4-23.2), bandemia (OR, 7.0; 95% CI, 1.6-30.3), and serum
      creatinine (OR, 1.4; 95% CI, 1.1-1.8). The common sources of infection were the
      lower respiratory tract (30.3%), urinary tract (49.3%), skin or soft tissue
      (12.0%), and intra-abdominal (6.3%). CONCLUSIONS: Cancer history, bandemia, and
      serum creatinine level are three independent mortality predictors for patients
      with infection-precipitated hyperglycemic crises. These predictors are both
      readily available and valuable for physicians making decisions about risk
      stratification, treatment, and disposition.

PMID- 23866066
TI  - TMEM16A alternative splicing coordination in breast cancer.
AB  - BACKGROUND: TMEM16A, also known as Anoctamin-1, is a calcium-activated chloride
      channel gene overexpressed in many tumors. The role of TMEM16A in cancer is not
      completely understood and no data are available regarding the potential
      tumorigenic properties of the multiple isoforms generated by alternative splicing
      (AS). METHODS: We evaluated TMEM16A AS pattern, isoforms distribution and
      Splicing Coordination (SC), in normal tissues and breast cancers, through a semi
      quantitative PCR-assay that amplifies transcripts across three AS exons, 6b, 13
      and 15. RESULTS: In breast cancer, we did not observe an association either to AS
      of individual exons or to specific TMEM16A isoforms, and induced expression of
      the most common isoforms present in tumors in the HEK293 Flp-In Tet-ON system had
      no effect on cellular proliferation and migration. The analysis of splicing
      coordination, a mechanism that regulates AS of distant exons, showed a
      preferential association of exon 6b and 15 in several normal tissues and tumors:
      isoforms that predominantly include exon 6b tend to exclude exon 15 and vice
      versa. Interestingly, we found an increase in SC in breast tumors compared to
      matched normal tissues. CONCLUSIONS: As the different TMEM16A isoforms do not
      affect proliferation or migration and do not associate with tumors, our results
      suggest that the resulting channel activities are not directly involved in cell
      growth and motility. Conversely, the observed increase in SC in breast tumors
      suggests that the maintenance of the regulatory mechanism that coordinates
      distant alternative spliced exons in multiple genes other than TMEM16A is
      necessary for cancer cell viability.

PMID- 23866068
TI  - Fruit and vegetable intake and risk of CHD: results from prospective cohort
      studies of Chinese adults in Shanghai.
AB  - The protective effects of fruits and vegetables against CHD have been suggested
      by many epidemiological studies among Western populations. However, prospective
      data are lacking for Asian populations. In the present study, we examined the
      associations of fruit and vegetable intake with CHD incidence among 67 211 women
      (aged 40-70 years) and 55 474 men (aged 40-74 years) living in Shanghai, China.
      Food intake was assessed using validated FFQ through in-person interviews.
      Coronary events (non-fatal myocardial infarction or fatal CHD) were identified by
      biennial home visits and further confirmed by medical record review. During a
      mean follow-up period of 9.8 and 5.4 years, 148 events in women and 217 events in
      men were documented and verified. After adjustment for potential confounders,
      women in the highest quartile of total fruit and vegetable intake (median 814
      g/d) had a hazard ratio (HR) of 0.62 (95 % CI 0.38, 1.02) for CHD (P for trend =
      0.04) compared with those in the lowest quartile (median 274 g/d). This
      association was primarily driven by fruits (HR for the highest v. the lowest
      intake in women: 0.62, 95 % CI 0.37, 1.03). The strength of the association was
      attenuated after further controlling for history of diabetes or hypertension. For
      men, no significant association was found for fruit and vegetable intake when
      analysed either in combination or individually. The present findings suggest that
      a high consumption of fruits may reduce CHD risk in Chinese women. 

PMID- 23866069
TI  - Shame, perceived knowledge and satisfaction associated with mental health as
      predictors of attitude patterns towards help-seeking.
AB  - Aims. To examine stigma- and knowledge-related barriers to help-seeking among
      members of the general population. Methods. In a representative survey of young
      to middle-aged Swiss adults (n = 8875), shame about a potential own mental
      illness, perceived knowledge about and satisfaction with one's mental health,
      psychiatric symptoms and attitudes towards help-seeking were assessed. Results. A
      latent profile analysis of all participants yielded two groups with different
      attitudes towards help-seeking. Relative to the majority, a one-in-four subgroup
      endorsed more negative attitudes towards seeking professional help, including
      psychiatric medication, and was characterized by more shame, less perceived
      knowledge, higher satisfaction with their mental health, younger age, male gender
      and lower education. Among participants with high symptom levels (n = 855), a
      third subgroup was reluctant to seek help in their private environment and
      characterized by high symptoms as well as low satisfaction with their mental
      health. Conclusions. Shame as an emotional proxy of self-stigma as well as poor
      subjective mental health literacy may be independent barriers to help-seeking.
      Interventions to increase mental health service use could focus on both variables
      and on those individuals with more negative views about professional help, in the
      general public as well as among people with a current mental illness. 

PMID- 23866070
TI  - Plasma levels of the arterial wall protein fibulin-1 are associated with carotid
      femoral pulse wave velocity: a cross-sectional study.
AB  - BACKGROUND: The arterial system in diabetic patients is characterized by
      generalized non-atherosclerotic alterations in the vascular extracellular matrix
      causing increased arterial stiffness compared with subjects without diabetes. The
      underlying pathophysiology remains elusive. The elastin-associated extracellular
      matrix protein, fibulin-1, was recently found in higher concentrations in the
      arterial wall and in plasma in patients with long duration type 2 diabetes.
      Furthermore, plasma fibulin-1 independently predicted total mortality and was
      associated with pulse pressure, an indirect measure of arterial stiffness.
      Whether plasma fibulin-1 is associated with arterial stiffness at earlier phases
      of type 2 diabetes has not been determined. METHODS: In this cross-sectional
      study, we examined 90 patients with recently diagnosed type 2 diabetes (< 5
      years) and 90 gender- and age-matched controls. Plasma fibulin-1 was measured
      immunochemically. Arterial stiffness was assessed by carotid-femoral Pulse Wave
      Velocity (PWV). Differences in means were assessed by t-tests. Associations were
      assessed by multivariate regression analyses. RESULTS: Plasma fibulin-1 levels
      were lower in the diabetic group compared with the control group, 93 +/- 28 vs
      106 +/- 30 MUg/mL, p = 0.005. In unadjusted analysis of the total study sample,
      plasma fibulin-1 was not associated with PWV, p = 0.46. However, with adjustment
      for the confounders age, gender, mean blood pressure, heart rate, body mass
      index, diabetes and glomerular filtration rate, a 10 MUg/mL increase in plasma
      fibulin was associated with 0.09 +/- 0.04 m/s increase in PWV, p < 0.05. In
      subgroup analysis, plasma fibulin-1 was associated with PWV in the diabetes
      group, (0.16 +/- 0.07 m/s increase in PWV per 10 MUg/mL increase in plasma
      fibulin-1, p<0.05), but not controls, beta = 0.021 +/- 0.057 m/s per 10 MUg/mL, p
      = 0.70. The association remained significant in the diabetes group after
      adjustment for covariates, p < 0.05. CONCLUSIONS: Plasma fibulin-1 is
      independently associated with PWV. Yet, as the plasma level of fibulin-1 was
      lower in patients with recently diagnosed type 2 diabetes than in healthy
      controls, plasma fibulin-1 levels are not a simple marker of the degree of
      arterial stiffening. Further studies are needed to determine the exact role of
      fibulin-1 in arterial stiffness and cardiovascular risk in patients with type 2
      diabetes.

PMID- 23866071
TI  - Juvenile hormone regulation of Drosophila aging.
AB  - BACKGROUND: Juvenile hormone (JH) has been demonstrated to control adult lifespan
      in a number of non-model insects where surgical removal of the corpora allata
      eliminates the hormone's source. In contrast, little is known about how juvenile
      hormone affects adult Drosophila melanogaster. Previous work suggests that
      insulin signaling may modulate Drosophila aging in part through its impact on
      juvenile hormone titer, but no data yet address whether reduction of juvenile
      hormone is sufficient to control Drosophila life span. Here we adapt a genetic
      approach to knock out the corpora allata in adult Drosophila melanogaster and
      characterize adult life history phenotypes produced by reduction of juvenile
      hormone. With this system we test potential explanations for how juvenile hormone
      modulates aging. RESULTS: A tissue specific driver inducing an inhibitor of a
      protein phosphatase was used to ablate the corpora allata while permitting normal
      development of adult flies. Corpora allata knockout adults had greatly reduced
      fecundity, inhibited oogenesis, impaired adult fat body development and extended
      lifespan. Treating these adults with the juvenile hormone analog methoprene
      restored all traits toward wildtype. Knockout females remained relatively long
      lived even when crossed into a genotype that blocked all egg production. Dietary
      restriction further extended the lifespan of knockout females. In an analysis of
      expression profiles of knockout females in fertile and sterile backgrounds, about
      100 genes changed in response to loss of juvenile hormone independent of
      reproductive state. CONCLUSIONS: Reduced juvenile hormone alone is sufficient to
      extend the lifespan of Drosophila melanogaster. Reduced juvenile hormone limits
      reproduction by inhibiting the production of yolked eggs, and this may arise
      because juvenile hormone is required for the post-eclosion development of the
      vitellogenin-producing adult fat body. Our data do not support a mechanism for
      juvenile hormone control of longevity simply based on reducing the physiological
      costs of egg production. Nor does the longevity benefit appear to function
      through mechanisms by which dietary restriction extends longevity. We identify
      transcripts that change in response to juvenile hormone independent of
      reproductive state and suggest these represent somatically expressed genes that
      could modulate how juvenile hormone controls persistence and longevity.

PMID- 23866072
TI  - Epiphyseal union of the cervical vertebral centra: its relationship to skeletal
      age and maturation of thoracic vertebral centra.
AB  - Epiphyseal union stages for cervical vertebral centra (ring epiphyses) were
      documented for 55 individuals (females and males, ages 14-27 years) from the
      Terry Collection, using the Albert and Maples method 1, to examine both its
      relationship to age at death and to thoracic data collected from the same
      individuals using the same method. Results showed a moderate correlation between
      cervical ring union and age (r = 0.63, p = 0.000), and a fairly low correlation
      between cervical and thoracic ring union (r = 0.41, p = 0.002). Paired samples t
      tests yielded a statistically significant difference between cervical and
      thoracic union mean values (p = 0.01). Union progressed earlier in cervical
      vertebrae and in females. Results indicated fairly substantial variation in both
      sexes. Findings may serve as a basic guideline for estimating a general age range
      at death for unknown skeletal remains and to corroborate findings from other
      skeletal age indicators.

PMID- 23866073
TI  - The WHO simulation initiative: improving global health partnerships.

PMID- 23866074
TI  - Asymmetric DNA-search dynamics by symmetric dimeric proteins.
AB  - We focus on dimeric DNA-binding proteins from two well-studied families: orthodox
      type II restriction endonucleases (REs) and transcription factors (TFs).
      Interactions of the protein's recognition sites with the DNA and, particularly,
      the contribution of each of the monomers to one-dimensional (1D) sliding along
      nonspecific DNA were studied using computational tools. Coarse-grained molecular
      dynamics simulations of DNA scanning by various TFs and REs provide insights into
      how the symmetry of a homodimer can be broken while they nonspecifically interact
      with DNA. The characteristics of protein sliding along DNA, such as the average
      sliding length, partitioning between 1D and 3D search, and the one-dimensional
      diffusion coefficient D1, strongly depend on the salt concentration, which in
      turn affects the probability of the two monomers adopting a cooperative symmetric
      sliding mechanism. Indeed, we demonstrate that maximal DNA search efficiency is
      achieved when the protein adopts an asymmetric search mode in which one monomer
      slides while its partner hops. We find that proteins classified as TFs have a
      higher affinity for the DNA, longer sliding lengths, and an increased probability
      of symmetric sliding in comparison with REs. Moreover, TFs can perform their
      biological function over a much wider range of salt concentrations than REs. Our
      results demonstrate that the different biological functions of DNA-binding
      proteins are related to the different nonspecific DNA search mechanisms they
      adopt. 

PMID- 23866075
TI  - Compulsive shouting (klazomania) responsive to electroconvulsive therapy.

PMID- 23866076
TI  - Correlates of apathy during the first year after traumatic brain injury.

PMID- 23866077
TI  - Pulmonary benign metastasizing leiomyoma from uterine leiomyoma.
AB  - BACKGROUND: Benign metastasizing leiomyoma (BML) occurs in a low proportion of
      uterine leiomyomas and treatment methods for BML are diverse and controversial.
      The study introduces preliminary experiences in the diagnosis and treatment of
      BML with the purpose of finding a suitable management strategy for these
      patients. METHODS: Three patients with BML were treated in our department from
      April 2008 to July 2012. Each of these patients presented with multiple nodules
      in both lungs, where we performed video-assisted thoracoscopic wedge resection to
      harvest enough tissue for histopathologic and immunohistochemical examination.
      The patients were treated with medical castration or surgical castration after
      the diagnosis of BML. RESULTS: The ultimate pathologic results ruled out the
      possibility of leiomyosarcoma and other metastatic diseases, and confirmed that
      the pulmonary lesions were BML. The lung lesions remained stable in two patients
      who were treated by surgical castration, and the lung nodules regressed in one
      patient treated with gonadotropin-releasing hormone analogues. CONCLUSIONS: The
      diagnosis of BML is based on the medical history of uterine myomas and
      histopathologic and immunohistochemical examination of lung nodules. Video
      assisted thoracoscopic wedge resection is the best way to harvest tissue for
      diagnosis. The better outcomes in BML seem to call for medical intervention,
      either chemical or surgical, after diagnosis is made.

PMID- 23866079
TI  - Hear today, not gone tomorrow? An exploratory longitudinal study of auditory
      verbal hallucinations (hearing voices).
AB  - BACKGROUND: Despite an increasing volume of cross-sectional work on auditory
      verbal hallucinations (hearing voices), there remains a paucity of work on how
      the experience may change over time. AIMS: The first aim of this study was to
      attempt replication of a previous finding that beliefs about voices are enduring
      and stable, irrespective of changes in the severity of voices, and do not change
      without a specific intervention. The second aim was to examine whether voice
      hearers' interrelations with their voices change over time, without a specific
      intervention. METHOD: A 12-month longitudinal examination of these aspects of
      voices was undertaken with hearers in routine clinical treatment (N = 18).
      RESULTS: We found beliefs about voices' omnipotence and malevolence were stable
      over a 12-month period, as were styles of interrelating between voice and hearer,
      despite trends towards reductions in voice-related distress and disruption.
      However, there was a trend for beliefs about the benevolence of voices to
      decrease over time. CONCLUSIONS: Styles of interrelating between voice and hearer
      appear relatively stable and enduring, as are beliefs about the voices'
      malevolent intent and power. Although there was some evidence that beliefs about
      benevolence may reduce over time, the reasons for this were not clear. Our
      exploratory study was limited by only being powered to detect large effect sizes.
      Implications for clinical practice and future research are discussed.

PMID- 23866078
TI  - Intraperitoneal administration of AAV9-shRNA inhibits target gene expression in
      the dorsal root ganglia of neonatal mice.
AB  - BACKGROUND: There is considerable interest in inducing RNA interference (RNAi) in
      neurons to study gene function and identify new targets for disease intervention.
      Although short interfering RNAs (siRNAs) have been used to silence genes in
      neurons, in vivo delivery of RNAi remains a major challenge, especially by
      systemic administration. We have developed a highly efficient method for in vivo
      gene silencing in dorsal root ganglia (DRG) by using short hairpin RNA-expressing
      single-stranded adeno-associated virus 9 (ssAAV9-shRNA). RESULTS: Intraperitoneal
      administration of ssAAV9-shRNA to neonatal mice resulted in highly effective and
      specific silencing of a target gene in DRG. We observed an approximately 80%
      reduction in target mRNA in the DRG, and 74.7% suppression of the protein was
      confirmed by Western blot analysis. There were no major side effects, and the
      suppression effect lasted for more than three months after the injection of
      ssAAV9-shRNA. CONCLUSIONS: Although we previously showed substantial inhibition
      of target gene expression in DRG via intrathecal ssAAV9-shRNA administration,
      here we succeeded in inhibiting target gene expression in DRG neurons via
      intraperitoneal injection of ssAAV9-shRNA. AAV9-mediated delivery of shRNA will
      pave the way for creating animal models for investigating the molecular biology
      of the mechanisms of pain and sensory ganglionopathies.

PMID- 23866080
TI  - Rivaroxaban and other non-vitamin K antagonist oral anticoagulants in the
      emergency treatment of thromboembolism.
AB  - Pulmonary embolism (PE) is potentially fatal and often requires emergency
      management. Because PE associated with shock and/or hypotension carries a high
      risk of sudden death, emergency clinicians must rapidly make a diagnosis and
      initiate appropriate therapeutic strategies, usually involving anticoagulant
      treatment. Traditional anticoagulants, such as heparins and vitamin K
      antagonists, although effective and recommended by guidelines, are associated
      with limitations. Several targeted, orally administered anticoagulants that may
      overcome some of these constraints have been developed recently and undergone
      analysis in randomised, phase III clinical trials. Rivaroxaban, a direct factor
      Xa inhibitor, was non-inferior to standard therapy with enoxaparin plus a vitamin
      K antagonist for the prevention of recurrent, symptomatic venous thromboembolism
      (VTE) in patients with acute PE and led to a 50% reduction in major bleeding.
      Dabigatran, a direct thrombin inhibitor, was also non-inferior to standard
      therapy for the prevention of recurrent VTE or VTE-related death when given after
      a parenteral anticoagulant and had a similar incidence of major bleeding. The
      results of a phase III study of apixaban, another direct factor Xa inhibitor, for
      the acute treatment of VTE are expected in the near future. Rivaroxaban is now
      approved in Europe and the US for the treatment of acute PE and prevention of
      recurrent VTE. This article reviews the current guidance on the treatment of PE
      with special focus on the emergency setting, and considers data regarding
      rivaroxaban and the other non-vitamin K antagonist oral anticoagulants and their
      potential role, including patients who are and are not appropriate for treatment
      with these agents. Issues such as drug interactions, reversal of anticoagulant
      effect and coagulation monitoring are also discussed. 

PMID- 23866082
TI  - Drug-reaction eosinophilia and systemic symptoms and drug-induced
      hypersensitivity syndrome.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug
      induced hypersensitivity syndrome (DIHS), is a rare, severe cutaneous adverse
      reaction characterised by fever, rash, lymphadenopathy, eosinophilia and/or other
      leukocyte abnormalities, and internal organ involvement and often has a relapsing
      remitting course despite withdrawal of the drug. The drugs that are most
      implicated include aromatic anticonvulsants, allopurinol, sulphonamides,
      antiretrovirals (abacavir and nevirapine), and minocycline. The pathogenesis of
      DRESS/DIHS is far from clear but probably involves a combination of impaired
      pharmacokinetics and the accumulation of drug metabolites, the sequential
      reactivation of the herpesvirus family and genetic susceptibility conferred by
      the association with certain human leukocyte antigen (HLA) class I alleles. The
      strong association between abacavir and HLA-B*5701 has enabled pharmacogenetics
      screening to be employed successfully to minimise the occurrence of
      hypersensitivity. A prolonged course of oral corticosteroids is required to treat
      DRESS/DIHS, given the relapsing-remitting nature of the condition with i.v.
      immunoglobulin and valgangciclovir reserved for refractory or life-threatening
      cases. 

PMID- 23866081
TI  - Lyn, a Src family kinase, regulates activation of epidermal growth factor
      receptors in lung adenocarcinoma cells.
AB  - BACKGROUND: Activation of receptors for growth factors on lung epithelial cells
      is essential for transformation into tumor cells, supporting their viability and
      proliferation. In most lung cancer patients, EGFR is constitutively activated
      without evidence of mutation. Defining mechanisms for constitutive activation of
      EGFR could elucidate additional targets for therapy of lung cancers. METHODS: The
      approach was to identify lung cancer cell lines with constitutively activated
      EGFR and use systematic selection of inhibitors to evaluate their effects on
      specific EGFR phosphorylations and downstream signaling pathways. Interactions
      between receptors, kinases, and scaffolding proteins were investigated by co
      immunoprecipitation plus Western blotting. RESULTS: The results revealed a
      dependence on Src family of tyrosine kinases for downstream signaling and cell
      growth. Lyn, a Src family kinase functional in normal and malignant B
      lymphocytes, was a defining signal transducer required for EGFR signaling in
      Calu3 cell line. Src family kinase activation in turn, was dependent on
      PKCbetaII. Lyn and PKC exist in membrane complexes of RACK1 and in association
      with EGFR which pairs with other receptor partners. Silencing of Lyn expression
      with interfering siRNA decreased EGFR activation and cell viability. CONCLUSIONS:
      The importance of Src family kinases and PKCbetaII in the initiation of the EGFR
      signaling pathway in lung tumor cells was demonstrated. We conclude that
      phosphorylation of EGFR is mediated through PKCbetaII regulation of Lyn
      activation, and occurs in association with RACK1 and Cbp/PAG proteins. We suggest
      that protein complexes in cell membranes, including lipid rafts, may serve as
      novel targets for combination therapies with EGFR and Src Family Kinase
      inhibitors in lung cancer.

PMID- 23866083
TI  - Establishing the optimal body mass index - body esteem relationship in young
      adolescents.
AB  - BACKGROUND: This study sought to compare the utility of either inverted body mass
      index or body mass index to optimise the relationship with body esteem in young
      adolescents Design: The study was cross sectional in design and assessed body
      esteem and weight status in 756 young adolescents (394 boys, 362 girls, mean age
      +/- S.D. 11.4 +/- 1.6 years). METHODS: Body esteem was determined using the body
      esteem scale for children. Height and body mass were measured directly. Body mass
      index was determined as kg/m2 and iBMI as cm2/kg. RESULTS: Results indicated that
      the association between iBMI and body esteem was curvilinear in nature and iBMI
      was the better predictor of body esteem (P=.001) predicting 21.3% of the variance
      in body esteem scores compared to 20.5% using BMI (P=.001). When split by gender,
      the curvilinear relationship was still evident but significantly different
      between boys and girls although iBMI remained a better predictor of body esteem
      compared to BMI in both boys and girls. The peak differed between gender groups
      with the association between iBMI and body esteem peaking at 642 cm2/kg for boys
      and 800.64 cm2/kg for girls. CONCLUSION: This study suggests that iBMI is a
      better predictor of body esteem in young adolescents, and that the association
      between body esteem and iBMI is curvilinear in nature. However, the peak of body
      esteem scores occured at a lower degree of leanness for boys compared to girls
      and indicated that the point at which body esteem scores are highest for girls is
      at a point of extreme leanness whereas the peak for boys was within the values
      considered as 'normal' on the leanness to obesity continuum. iBMI may therefore
      be a useful measure of leanness for future studies examining the association
      between overweight/obesity and body esteem in young adolescents.

PMID- 23866084
TI  - Bilateral hippocampal increase following first-episode psychosis is associated
      with good clinical, functional and cognitive outcomes.
AB  - BACKGROUND: Hippocampal pathology has been proposed to underlie clinical,
      functional and cognitive impairments in schizophrenia. The hippocampus is a
      highly plastic brain region; examining change in volume, or change bilaterally,
      over time, can advance understanding of the substrate of recovery in psychosis.
      METHOD: Magnetic resonance imaging and outcome data were collected at baseline
      and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched
      controls, to investigate whether poorer outcomes are associated with loss of
      global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over
      time, as a marker of hippocampal plasticity was hypothesized to be associated
      with better outcomes. Regression analyses were performed on: (i) clinical and
      functional outcomes with grey matter volume change and BHI as predictor
      variables; and (ii) cognitive outcome with BHI as predictor. RESULTS: BHI was
      present in 29% of psychosis participants. There was no significant grey matter
      loss over time in either patient or control groups. Less severe illness course
      and lesser symptom severity were associated with BHI, but not with grey matter
      change. Employment and global function were associated with BHI and with less
      grey matter loss. Superior delayed verbal recall was also associated with BHI.
      CONCLUSIONS: BHI occurs in a minority of patients following their first psychotic
      episode and is associated with good outcome across clinical, functional and
      cognitive domains.

PMID- 23866085
TI  - HIV prevalence in persons with severe mental illness in Uganda: a cross-sectional
      hospital-based study.
AB  - BACKGROUND: In Uganda, a previous study reported high HIV prevalence in persons
      with severe mental illness (SMI) compared to the general population, suggesting
      that persons with SMI might constitute a high-risk group for HIV. However, the
      study included first-time psychiatric admissions only, a group whose HIV
      prevalence may not reflect the prevalence in persons with SMI in general. We
      determined prevalence and correlates of HIV in both first-time and previous
      psychiatric admissions, in a psychiatric hospital in Uganda. METHODS: Cross
      sectional study of HIV status in persons consecutively discharged from
      psychiatric admission wards in Butabika hospital, Uganda. INCLUSION CRITERIA: age
      18-49 years; schizophrenia, bipolar disorder, depression, or other non-substance
      use-related psychosis; Luganda or English proficiency. Exclusion criterion:
      Mental incapacity to give informed consent. Participants were HIV-tested, and
      interviewed using a structured questionnaire. Data were analysed using logistic
      regression. RESULTS: HIV prevalence was 11.3% (CI 8.8-13.8) overall, 7.3% (CI 4.1
      10.5) in men and 14.3% (CI 10.6-18.0) in women. Females had higher risk of HIV
      infection than males (OR 2.10; CI 1.20-3.67), after adjustment for age. Older
      patients had higher risk of HIV infection than younger patients (40-49 vs. 18-29
      years: OR 2.34; CI 1.27-4.32), after adjustment for sex. Place of residence,
      marital status, income, education, occupation, psychiatric diagnosis and history
      of previous admission were not associated with HIV infection, after adjustment
      for sex and age. The above associations did not significantly differ between men
      and women. CONCLUSIONS: Persons admitted for SMI in Uganda have higher HIV
      prevalence than persons in the general population, irrespective of previous
      admissions. The excess HIV prevalence is mainly confined to women. The findings
      call for the integration of HIV prevention, testing and care with mental health
      services in settings with generalized HIV epidemics. Moreover, further research
      is needed to clarify the mechanisms underlying the increased HIV prevalence in
      women with SMI in Uganda, and to identify effective community-based interventions
      for this vulnerable group.

PMID- 23866086
TI  - Synthesis and application of (13)C-labeled 2-acetyl-4-((1R,2S,3R)-1,2,3,4
      tetrahydroxybutyl)imidazole (THI), an immunosuppressant observed in caramel food
      colorings.
AB  - 2-Acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI) is a minor toxic
      contaminant observed in caramel food colorings and was shown to exert
      immunosuppressant activity when fed to rodents. Because of this toxicity, maximum
      levels of THI in caramel food colorings have been defined by international and
      European authorities. Several reports of THI analysis using external
      standardization have been published for liquid foods such as beers and soft
      drinks. However, no suitable internal standard has yet been described allowing
      THI analysis in more complex samples. In this paper we describe the preparation
      of a labeled [(13)C6]THI analogue and its application for the successful
      validation of the first stable isotope dilution assay (SIDA) of THI in caramel
      food colorings. A brief survey of THI levels in commercially available caramel
      class III (E 150c) and IV (E 150d) food colorings is also included, corroborating
      that THI occurs only in caramel class III food colorings. 

PMID- 23866087
TI  - Real-world utilization patterns and outcomes of colesevelam hcl in the ge
      electronic medical record.
AB  - BACKGROUND: In randomized controlled trials (RCTs), colesevelam HCI, added to
      other anti-diabetic therapy, reduced hemoglobin A1C by approximately 0.3% to 0.4%
      over 16- to 26-weeks compared with an increase of approximately 0.1% to 0.2% for
      placebo, for a placebo-adjusted treatment effect of approximately 0.5%. Evidence
      on real-world effectiveness is unknown. This retrospective cohort study examined
      A1C changes following colesevelam HCL initiation in patients with diabetes,
      regardless of concomitant anti-diabetic medication use. METHODS: 2000-2011 GE
      Centricity electronic medical records data were used to identify patients with
      type 2 diabetes mellitus (T2DM) aged 18 or older initiating colesevelam HCL. The
      sample was further restricted to uncontrolled patients with database activity >=
      395 days before and after colesevelam HCL initiation, A1C > 7% during 90 days
      prior to starting colesevelam HCL, without prior use of bile acid sequestrants,
      and with at least one A1C result between 42 to 210 days after initiation. Three
      overlapping time intervals were created for A1C measurement, including 16-weeks,
      26-weeks, and 52-weeks following therapy initiation. The last observed A1C lab
      measurement during each interval was used to define change from baseline. Mean
      change in A1C was examined using paired t-tests. Sensitivity analyses considered
      only patients who remained on colesevelam HCL through each respective measurement
      period, as well as the effect of concomitant diabetes medications. RESULTS: Of
      1,709,393 patients in the GE database with T2DM, 1,747 met inclusion criteria.
      The cohort was 58% female, 38% age >= 65, and the majority was white. For the 16
      week endpoint (N = 1,385), A1C dropped from a mean of 8.22% to 7.75% (mean change
      -0.47%; P < 0.0001). For the 26- and 52-week endpoints (N = 1,747), A1C dropped
      from a mean of 8.25% to 7.81% (mean change -0.44%; P < 0.0001) and 8.25% to 7.79%
      (mean change -0.46%; P < 0.0001), respectively. Sensitivity analyses showed that
      A1C reductions were of similar direction and magnitude for patients who remained
      on treatment, and for the subgroups of patients stratified by receipt of
      concomitant T2DM treatments. CONCLUSIONS: The 0.44% to 0.47% A1C reduction
      observed in this study was similar to the reduction observed in RCTs, supporting
      the real-world effectiveness of colesevelam HCL in reducing A1C.

PMID- 23866088
TI  - Desiccation resistance of wild and mass-reared Bactrocera tryoni (Diptera:
      Tephritidae).
AB  - In pest management programmes that incorporate the sterile insect technique
      (SIT), the ability of mass-reared insects to tolerate dry conditions may
      influence their survival after release in the field. In the present study,
      desiccation resistance of adult mass-reared Queensland fruit flies, Bactrocera
      tryoni (Frogatt) (Diptera: Tephritidae), that are routinely released in SIT
      programmes was compared with that of wild flies at 1, 10 and 20 days after adult
      eclosion. Under dry conditions without access to food or water, longevity of mass
      reared B. tryoni was significantly less than that of their wild counterparts.
      Desiccation resistance of mass-reared flies declined monotonically with age, but
      this was not the case for wild flies. The sharp decline in desiccation resistance
      of mass-reared flies as they aged was likely explained by decreased dehydration
      tolerance. As in an earlier study, desiccation resistance of females was
      significantly lower than that of males but this was particularly pronounced in
      mass-reared females. Female susceptibility to dry conditions corresponded with
      declining dehydration tolerance with age and associated patterns of reproductive
      development, which suggests that water content of their oocyte load is not
      available for survival during periods of water stress. 

PMID- 23866089
TI  - Mechanism of action of ketamine.
AB  - Ketamine induces rapid-onset and short-duration improvement in depressive and
      suicidal symptoms in both treatment-resistant unipolar depression and bipolar
      depression, and also reduces chronic pain after short intravenous infusions. In
      order to develop long-acting oral agents with the same clinical effects, the
      pharmacologic mechanism of action must be understood, and the leading hypotheses
      are discussed here.

PMID- 23866090
TI  - Controversies in treating bipolar depression.

PMID- 23866092
TI  - Integrative acupoint stimulation to alleviate postoperative pain and morphine
      related side effects: a sham-controlled study.
AB  - BACKGROUND: Although it can be reduced, postoperative pain remains a problem.
      Acupressure with electric stimulation may be more effective for postoperative
      pain management than acupressure alone. OBJECTIVES: This study aimed to evaluate
      the effects of integrative acupoint stimulation (IAS) on the relief of
      postoperative pain and on the reduction of morphine-related side effects. DESIGN:
      A single-blinded, sham-controlled study with three groups. SETTING: An orthopedic
      ward in a 2900-bed teaching medical center. PARTICIPANTS: Forty-five subjects in
      each of three groups. METHODS: Each subject received a multimedia course on
      patient-controlled analgesia (PCA) before surgery to learn about the use of
      narcotic analgesics and the operation of the PCA device. Treatment was as
      follows: (1) for the IAS group, auricular acupressure combined with
      transcutaneous electric acupoint stimulation (TEAS) at the true acupoint; (2) for
      the sham group, acupoint stimulation in the same manner but at a sham acupoint or
      without embedding seeds and pressure; (3) for the control group, no IAS
      intervention. RESULTS: Pain scores were significantly lower in the IAS group than
      the other two groups at 2h and 4h after returning to the ward, and 24h after
      surgery. The analgesic requirement during the 72h after surgery and the overall
      incidence of morphine-related side effects were significantly lower in the IAS
      group. CONCLUSION: The study demonstrates that combined auricular acupressure and
      TEAS decreased postoperative pain, the use of equianalgesic morphine, and
      morphine-related side effects. IAS provides better analgesia when used in
      conjunction with PCA after lumbar spine surgery and can be regarded as a
      component of multimodal analgesia.

PMID- 23866093
TI  - Preferences and priorities for ongoing and end-of-life care: a qualitative study
      of older people with dementia resident in care homes.
AB  - BACKGROUND: The older person with dementia has a limited life expectancy and the
      dying trajectory can be protracted and unpredictable. For good end-of-life care,
      early communication, exploration of residents' wishes, and identification of
      someone who can represent them, are important. In care homes the timing of these
      discussions, and who is involved is variable. Person-centred approaches to
      dementia care assume that people with dementia can actively participate in
      decisions about their lives. Less well understood is how this can inform end-of
      life care decision making and complement information provided in advance care
      plans completed prior to, or at the point of admission to a care home.
      OBJECTIVES: To explore how older people with dementia discuss their priorities
      and preferences for end-of-life care. METHODS: An exploratory, qualitative study
      that used guided conversations with 18 people with dementia, living in six care
      homes. Participants were asked about their life in the care home, their health,
      thoughts for the future, and wishes surrounding end of life. Data were analysed
      thematically. RESULTS: People with dementia's accounts of life in the care home,
      what they valued, and the impact of having dementia on how they participated in
      decision making, provided key insights into care preferences. Three linked themes
      that had relevance for thinking and talking about end of life were identified:
      "dementia and decision making", "everyday relationships" and "place and purpose".
      Older people with dementia's accounts of everyday experiences of care, key
      relationships with family and care home staff members and whether they accepted
      the care home as their home demonstrated what was important for them now and for
      the future. CONCLUSION: For older people living with a diagnosis of dementia, the
      experience of living and dying in a care home is inextricably linked. End-of-life
      care planning and decision making by health care professionals, care home staff
      and family could be enriched by exploring and documenting the preoccupations, key
      relationships and wishes about everyday care of people with dementia.

PMID- 23866091
TI  - Dual renin-angiotensin system inhibition for prevention of renal and
      cardiovascular events: do the latest trials challenge existing evidence?
AB  - Circulatory and tissue renin-angiotensin systems (RAS) play a central role in
      cardiovascular (CV) and renal pathophysiology, making RAS inhibition a logical
      therapeutic approach in the prevention of CV and renal disease in patients with
      hypertension. The cardio- and renoprotective effects observed with angiotensin
      converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)
      monotherapy, together with the availability of a direct renin inhibitor (DRI),
      led to the investigation of the potential benefits of dual RAS inhibition. In
      small studies, ARB and ACE inhibitor combinations were shown to be beneficial in
      patients with CV or renal disease, with improvement in surrogate markers.
      However, in larger outcome trials, involving combinations of ACE inhibitors, ARBs
      or DRIs, dual RAS inhibition did not show reduction in mortality in patients with
      diabetes, heart failure, coronary heart disease or after myocardial infarction,
      and was in fact, associated with increased harm. A recent meta-analysis of all
      major trials conducted over the past 22 years involving dual RAS inhibition has
      clearly shown that the risk-benefit ratio argues against the use of dual RAS
      inhibition. Hence, the recent evidence clearly advocates against the use of dual
      RAS inhibition, and single RAS inhibition appears to be the most suitable
      approach to controlling blood pressure and improving patient outcomes.

PMID- 23866094
TI  - The regulation of Toll-like receptor 2 by miR-143 suppresses the invasion and
      migration of a subset of human colorectal carcinoma cells.
AB  - BACKGROUND: The Toll-like receptor 2 (TLR2)-driven tissue response may promote
      neoangiogenesis and tumour growth by mechanisms that are poorly understood.
      METHODS: We investigated the expression levels of TLR2 and associated-miRNAs in
      colorectal carcinoma (CRC) tissues and cell lines using real-time PCR, northern
      blotting and western blotting. Survival curver was generated by Log-Rank test and
      the role of TLR2 signalling in tumour invasion and migration was determined by
      transwell analysis kits. RESULTS: We observed that the tissues from CRC patients
      express relatively high levels of TLR2. Targeting TLR2 markedly reduces the
      invasion and migration of CRC cells. We also found that miR-143, a putative
      tumour suppressor that is down-regulated in CRC tissues, reduces the invasion and
      migration of CRC cells primarily via TLR2. Utilising a xenograft mouse model, we
      demonstrated that re-expression of miR-143 inhibits CRC cell colonisation in
      vivo. CONCLUSION: miR-143 blocks the TLR2 signalling pathway in human CRC cells.
      This knowledge may pave the way for new clinical applications utilising miR-143
      mimics in the treatment of patients with CRC.

PMID- 23866095
TI  - A review of published literature on emergency medicine training programs in low-
      and middle-income countries.
AB  - BACKGROUND: The objective of this review is to identify and critically evaluate
      the published literature on emergency medicine (EM) training programs in resource
      limited health-care settings in order to provide insight for developing EM
      training programs in such health systems. METHODS: A literature search was
      conducted up to the end of April 2011 using MEDLINE, EMBASE, The Cochrane
      Library, EBM Reviews, Healthstar and Web of Science databases, using the
      following search terms: Emergency Medicine, Emergency Medicine Services,
      Education Training Residency Programs, Emergency Medical Systems and Medical
      Education, without limitation to income countries as outlined in the World Bank
      World Trade Indicators classification 2009-2010 (World Trade Indicators Country
      Classification by Region and Income, July 2009-July 2010). As the intent of the
      review was to identify and critically evaluate the literature readily available
      (published) to LMICs developing EM programs, the gray literature was not
      searched. RESULTS: The search yielded 16 articles that met the final inclusion
      criteria. As the majority of articles provide a narrative description of the
      processes and building blocks used in developing the residency programs reported,
      we present our results in narrative format. By providing a summary of the lessons
      learned to date, we hope to provide a useful starting point for other resource
      limited settings interested in establishing emergency medicine specialty training
      programs and hope to encourage further information exchange on this matter.
      CONCLUSIONS: The results of the review indicate that EM training is in its
      infancy in resource-constrained health-care systems. There are few detailed
      reports of these programs successes and limitations, including efforts to
      optimize graduate retention. Despite the paucity of currently published data on
      the development of EM residency training programs in these settings, this review
      demonstrates the need for encouraging further information exchange to aid in such
      efforts, and the authors make specific recommendations to help guide future
      authors on reporting on such efforts.

PMID- 23866096
TI  - The predictive value of IL28B rs12979860, rs11881222 and rs8099917 polymorphisms
      and IP-10 in the therapeutic response of Egyptian genotype 4 patients.
AB  - Interleukin-28B (IL28B) polymorphisms have previously been reported to be
      strongly associated with spontaneous and treatment-induced HCV viral clearance.
      AIM: To assess the impact of four different IL28B polymorphisms and their
      haplotype combination and interferon-c inducible protein 10 (IP-10) in response
      to treatment in Egyptian genotype 4 patients. METHOD: 159 HCV-genotype 4 patients
      were included. All patients were treated with Peginterferon alph2a/Ribavirin for
      48 wk. The following polymorphisms rs12979860, rs11881222, rs8103142 and
      rs8099917 and rs80803142 of Il-28 were known to be associated with the sustained
      virological response. They were genotyped using the TaqMan assay. IP-10 was
      assessed by Eliza. RESULTS: The data indicated that all SNPs are within the Hardy
      Weinberg Equilibrium (HWE) except for rs8103142 (p=6.255(-9)), therefore it was
      excluded from the study since it deviates from HWE-P. The CC, AA and TT genotypes
      of rs12979860, rs11881222 and rs8099917 were the more frequent genotypes among
      the responders at RVR, EVR, ETR and SVR, respectively. The frequency of CC, CT,
      and TT genotype was 46.4%, 38.1% and 15.5% among responders of RVR, and was
      46.9%, 45.9% and 7.2 among responders of SVR for rs12979860, respectively. The
      relapse rate was 18.0% and 16.0 % during EVR and ETR, while the response rate was
      52.8%, 58.5%, 59.7% and 61.6% after 4, 12, 48 and 72 weeks of treatment. The
      transient virological response (TVR) was 6.9% among HCV patients. The results
      showed that the odds ratio and 95% CI of HCV genotype 4 patients to have a better
      sustained response to treatment (SVR) was 2.92, (1.83-4.68, p=2.01(-5)), 2.89
      (1.79-4.70, p=2.53(-5)), and 2.73 (0.21-0.65, p=0.0007) for those with the major
      allele "C" of rs12979860, the "A" allele of rs11881222, and the "T" allele of
      rs8099917, respectively. Furthermore, the positive predictive value (PPV) of the
      major homozygous alleles for SVR with better response to therapy was in the
      following order: 78.69%, 68.42%, and 32.14% with a positive likelihood ratio of
      1.95, 1.25, and 0.86 for rs12979860, rs11881222 and rs8099917, respectively. The
      haplotype formed between the 3 studied SNPs (rs12979860, rs11881222 and
      rs8099917) showed that two haplotypes (TGG and TGT) increased the probability of
      a poor response to therapy, but the CAT haplotype had the opposite effect.
      Multinomial logistic regression analysis revealed that the viral load and
      rs12979860 are the only significant actors involved in the efficacy of the
      treatment response among the cohort study. In addition, patients with SVR had
      significantly lower values of IP-10 than non-responder patients (NR), with a P
      value<=0.001. CONCLUSIONS: In genotype 4 cases, the IL28B SNPs rs12979860
      rs8099917, and rs11881222 are the strongest predictors of a response, while IP-10
      is a strong negative biomarker of a response. Accounting for this factor is
      important in the individualization of treatment and enhances the degree of
      predictiveness of the IL28 polymorphism in the final treatment outcome. The
      frequent distribution of C, A and T alleles of IL28 polymorphism are higher among
      TVR, which may reflect sensitivity to prolonged course.

PMID- 23866097
TI  - Serum calcium and risk of gastrointestinal cancer in the Swedish AMORIS study.
AB  - BACKGROUND: Observational studies have indicated that high calcium intake may
      prevent colorectal cancer, but as for randomized trials the results are
      inconclusive. Meanwhile, limited data on the link between serum calcium and
      cancer risk is available. We investigated the relation between serum calcium and
      risk of different gastrointestinal cancers in a prospective study. METHODS: A
      cohort based on 492,044 subjects with baseline information on calcium (mmol/L)
      and albumin (g/L) was selected from the Swedish Apolipoprotein MOrtality RISk
      (AMORIS) study. Multivariable Cox proportional hazard models were used to analyse
      associations between standardised levels, quartiles and age/sex-specific
      categories of serum calcium and risk of oesophageal, stomach, colon, rectal
      cancer and also colorectal cancer combined, while taking into account serum
      albumin and other comorbidities. RESULTS: During 12 years of follow-up, we
      identified 323 incident oesophageal cancers, 782 stomach cancers, 2519 colon
      cancers, and 1495 rectal cancers. A positive association was found between
      albumin-adjusted serum calcium and risk of oesophageal [HR: 4.82 (95% CI: 2.07 -
      11.19) for high compared to normal age-specific calcium levels] and colon cancer
      [e.g. HR: 1.07 (95% CI: 1.00 - 1.14) for every SD increase of calcium] as well as
      colorectal cancer [e.g. HR: 1.06 (95% CI: 1.02-1.11) for every SD increase of
      calcium] in women. In men there were similar but weaker non-statistically
      significant trends. CONCLUSION: The positive relation between serum calcium,
      oesophageal cancer and colorectal cancer calls for further studies including
      calcium regulators to evaluate whether there is a true link between calcium
      metabolism and development of gastrointestinal cancer.

PMID- 23866099
TI  - Psychiatric symptoms as a clinical presentation of Cushing's syndrome.
AB  - Cushing's syndrome can present with a spectrum of symptoms; however, it is less
      recognised that psychiatric symptoms can form part of the clinical presenting
      features. In the investigations for an organic cause for a psychiatric illness,
      Cushing's syndrome needs to be considered, especially if there are other features
      such as hirsutism or hypertension. In this article, the two cases reported
      demonstrate that a prompt diagnosis is not only important for psychiatric
      management but also crucial for timely institution of the necessary treatment of
      life-threatening causes of hypercortisolaemia such as metastatic adrenal
      carcinoma. 

PMID- 23866098
TI  - Frequency of nut consumption and mortality risk in the PREDIMED nutrition
      intervention trial.
AB  - BACKGROUND: Prospective studies in non-Mediterranean populations have
      consistently related increasing nut consumption to lower coronary heart disease
      mortality. A small protective effect on all-cause and cancer mortality has also
      been suggested. To examine the association between frequency of nut consumption
      and mortality in individuals at high cardiovascular risk from Spain, a
      Mediterranean country with a relatively high average nut intake per person.
      METHODS: We evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of
      3 interventions (Mediterranean diets supplemented with nuts or olive oil and
      control diet) in the PREDIMED ('PREvencion con DIeta MEDiterranea') study. Nut
      consumption was assessed at baseline and mortality was ascertained by medical
      records and linkage to the National Death Index. Multivariable-adjusted Cox
      regression and multivariable analyses with generalized estimating equation models
      were used to assess the association between yearly repeated measurements of nut
      consumption and mortality. RESULTS: During a median follow-up of 4.8 years, 323
      total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut
      consumption was associated with a significantly reduced risk of all-cause
      mortality (P for trend<0.05, all). Compared to non-consumers, subjects consuming
      nuts>3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard
      ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against
      cardiovascular and cancer mortality was observed. Participants allocated to the
      Mediterranean diet with nuts group who consumed nuts>3 servings/week at baseline
      had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66). CONCLUSIONS:
      Increased frequency of nut consumption was associated with a significantly
      reduced risk of mortality in a Mediterranean population at high cardiovascular
      risk.Please see related commentary: http://www.biomedcentral.com/1741
      7015/11/165. TRIAL REGISTRATION: Clinicaltrials.gov. International Standard
      Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5
      October 2005.

PMID- 23866100
TI  - Cognition in early relapsing-remitting multiple sclerosis: consequences may be
      relative to working memory.
AB  - The Relative Consequence Model proposes multiple sclerosis (MS) patients have a
      fundamental deficit in processing speed that compromises other cognitive
      functions. The present study examined the mediating role of processing speed,as
      well as working memory, in the MS-related effects on other cognitive functions
      for early relapsing-remitting patients. Seventy relapsing-remitting MS patients
      with disease duration not greater than 10 years and 72 controls completed tasks
      assessing processing speed, working memory, learning, and executive functioning.
      The possible mediating roles of speed and working memory in the MS-related
      effects on other cognitive functions were evaluated using structural equation
      modeling. Processing speed was not significantly related to group membership and
      could not have a mediating role. Working memory was related to group membership
      and functioned as a mediating/intervening factor. The results do not support the
      Relative Consequence Model in this sample and they challenge the notion that
      working memory impairment only emerges at later disease stages. The results do
      support a mediating/intervening role of working memory. These results were
      obtained for early relapsing-remitting MS patients and should not be generalized
      to the broader MS population. Instead, future research should examine the
      relations that exist at other disease stages.

PMID- 23866101
TI  - An extrapolation of Foucault's Technologies of the Self to effect positive
      transformation in the intensivist as teacher and mentor.
AB  - In critical care medicine, teaching and mentoring practices are extremely
      important in regard to attracting and retaining young trainees and faculty in
      this important subspecialty that has a scarcity of needed personnel in the USA.
      To this end, we argue that Foucault's Technologies of the Self is critical
      background reading when endeavoring to effect the positive transformation of
      faculty into effective teachers and mentors. 

PMID- 23866103
TI  - Online cognitive-based intervention for depression: exploring possible
      circularity in mechanisms of change.
AB  - BACKGROUND: This study investigates possible circularity in mechanisms of change
      in participants of Master Your Mood (MYM), a cognitive-based, online intervention
      for young adults with depressive symptoms. A previous study showed that MYM
      effectively reduced depression and anxiety and strengthened mastery. METHOD: We
      randomized 244 participants with depressive symptoms into MYM or a wait-list
      control condition. We explored the circularity hypothesis by several analyses.
      Correlations were computed to determine the association between (change in)
      depression and anxiety. Path analysis mediation models were used to explore
      whether change in anxiety and mastery mediated the intervention effect on
      depression, whether depression and mastery mediated the effect on anxiety and
      whether depression and anxiety mediated the effect on mastery. We used linear
      regression to explore whether early changes in anxiety predicted later changes in
      depression, and whether early changes in depression predicted later changes in
      anxiety. RESULTS: Co-morbidity between depression and anxiety was high (69.2%)
      and the association between depression and anxiety change was strong (r = 0.677,
      p < 0.01). Changes in anxiety and mastery mediated change in depression
      (mediation proportion 44%); changes in depression mediated change in anxiety
      (79%) and mastery (75%). We did not find an early change in anxiety predictive
      for a late change in depression, and vice versa. CONCLUSIONS: This study appears
      to confirm the hypothesized circularity in the recovery process. We found high co
      morbidity and strong correlation between depression and anxiety levels and bi
      directional relationships between potential mediators and outcomes. Early anxiety
      change scores were not predictive of late depression change scores, and vice
      versa.

PMID- 23866102
TI  - Acylcarnitine esters profiling of serum and follicular fluid in patients
      undergoing in vitro fertilization.
AB  - BACKGROUND: L-carnitine-mediated beta-oxidation of fatty acids has a well
      established role in energy supply of oocytes and embryos. Disturbed carnitine
      metabolism may impair the reproductive potential in IVF and can serve as a
      biomarker of pregnancy outcome. METHODS: Our study was performed between March
      24, 2011 and May 9, 2011. We performed 44 unselected IVF cycles, (aged 23-40
      years (mean: 32.3+/-5.1 years) and had BMI of 17.3-34.7 (mean: 23.80+/-4.9).
      Samples were also obtained from 18 healthy women of similar age admitted for
      minor elective surgery to serve as control for plasma carnitine profile. Serum
      and follicular fluid (FF) free carnitine (FC) and 20 major acylcarnitines (ACs)
      were measured by ESI/MS/MS method. RESULTS: Serum FC and AC levels in IVF
      patients were comparable to those in healthy control women. In FF FC and short
      chain AC concentrations were similar to those in maternal serum, however, the
      levels of medium-chain, and long-chain AC esters were markedly reduced (p<0.05).
      The serum to FF ratio of individual carnitine compounds increased progressively
      with increasing carbon chain length of AC esters (p<0.05). There was a marked
      reduction in total carnitine, FC and AC levels of serum and FF in patients with
      oocyte number of >9 and/or with embryo number of >6 as compared to the respective
      values of <9 and/or <6 (p<0.05). CONCLUSIONS: In IVF patients with better
      reproductive potential the carnitine/AC pathway appears to be upregulated that
      may result in excess carintine consumption and relative depletion of carnitine
      pool. Consequently, IVF patients may benefit from carnitine supplementation.

PMID- 23866104
TI  - Salivary pellicles on titanium and their effect on metabolic activity in
      Streptococcus oralis.
AB  - BACKGROUND: Titanium implants in the oral cavity are covered with a saliva
      derived pellicle to which early colonizing microorganisms such as Streptococcus
      oralis can bind. The protein profiles of salivary pellicles on titanium have not
      been well characterized and the proteins of importance for binding are thus
      unknown. Biofilm bacteria exhibit different phenotypes from their planktonic
      counterparts and contact with salivary proteins may be one factor contributing to
      the induction of changes in physiology. We have characterized salivary pellicles
      from titanium surfaces and investigated how contact with uncoated and saliva
      coated titanium surfaces affects metabolic activity in adherent cells of S.
      oralis. METHODS: Salivary pellicles on smooth titanium surfaces were desorbed and
      these, as well as purified human saliva, were subjected to two-dimensional gel
      electrophoresis and mass spectroscopy. A parallel plate flow-cell model was used
      to study binding of a fresh isolate of S. oralis to uncoated and saliva-coated
      titanium surfaces. Metabolic activity was assessed using the BacLight CTC
      Vitality Kit and confocal scanning laser microscopy. Experiments were carried out
      in triplicate and the results analyzed using Student's t-test or ANOVA. RESULTS:
      Secretory IgA, alpha-amylase and cystatins were identified as dominant proteins
      in the salivary pellicles. Selective adsorption of proteins was demonstrated by
      the enrichment of prolactin-inducible protein and absence of zinc-alpha2
      glycoprotein relative to saliva. Adherence of S. oralis to titanium led to an up
      regulation of metabolic activity in the population after 2 hours. In the presence
      of a salivary pellicle, this effect was enhanced and sustained over the following
      22 hour period. CONCLUSIONS: We have shown that adherence to smooth titanium
      surfaces under flow causes an up-regulation of metabolic activity in the early
      oral colonizer S. oralis, most likely as part of an adaptation to the biofilm
      mode of life. The effect was enhanced by a salivary pellicle containing sIgA,
      alpha-amylase, cystatins and prolactin-inducible protein which was, for the first
      time, identified as an abundant component of salivary pellicles on titanium.
      Further studies are needed to clarify the mechanisms underlying the effect of
      surface contact on metabolic activity as well as to identify the salivary
      proteins responsible for enhancing the effect.

PMID- 23866105
TI  - Variations in unmet need for contraception in Zambia: does ethnicity play a role?
AB  - Ethnicity has been found to be a significant indicator of social position, and
      many studies have also established that ethnicity is a significant determinant of
      contraceptive use. This study aims to examine whether ethnicity is an important
      predictor of unmet need for contraception. Analysis was based on data for 4343
      ever-married women drawn from the 2007 Zambia Demographic and Health Survey.
      Descriptive analysis indicates that in all ethnic groups except the Barotse and
      Tonga, women aged 15-49 years were married at an average age below 18. The
      highest mean number of children among the ethnic groups was 6.7, among the Bemba;
      the lowest was 5.9, among the Barotse. The highest proportion of women with an
      unmet need for contraception resided in the Eastern region. Multivariate logistic
      analyses reveal that children ever-born and region of residence were the most
      important predictors of unmet need for spacing, whereas for unmet need for
      limiting predictors were age at first marriage and partner's desire for children.
      Moreover, unmet need for spacing and limiting among women with secondary or
      higher education was significantly lower (47% and 50%, respectively) compared
      with those with no education. Ethnicity was not a significant predictor of unmet
      need for contraception. The findings stress the need for programmes aimed at
      enhancing the socioeconomic status of women.

PMID- 23866107
TI  - Should we go nuts about nuts?
AB  - Since the beginning of the 1990s, increasing evidence supports beneficial effects
      of nut consumption on health. A new analysis of the Spanish PREDIMED trial,
      published in BMC Medicine, has expanded our knowledge. The study showed that
      individuals eating nuts more than three times per week died less often from
      cardiovascular disease and cancer than non-consumers. The study also adds an
      important finding that previous epidemiological studies could not provide: a
      protective effect on premature mortality was only seen in the intervention group
      in which nut consumption increased during the 4.8 years of follow-up, not in the
      intervention group with additional olive oil consumption or in the control group.
      Nut consumption actually decreased during follow-up in the latter two groups.
      Questions remain to be answered on the quantity of nuts to be consumed for health
      benefits, on possible mechanisms of action, and on whether some types of nuts
      should be favored.Please see related research: http://www.biomedcentral.com/1741
      7015/11/164. 

PMID- 23866106
TI  - Lessons learned from child sexual abuse research: prevalence, outcomes, and
      preventive strategies.
AB  - Although child sexual abuse (CSA) is recognized as a serious violation of human
      well-being and of the law, no community has yet developed mechanisms that ensure
      that none of their youth will be sexually abused. CSA is, sadly, an international
      problem of great magnitude that can affect children of all ages, sexes, races,
      ethnicities, and socioeconomic classes. Upon invitation, this current publication
      aims at providing a brief overview of a few lessons we have learned from CSA
      scholarly research as to heighten awareness of mental health professionals on
      this utmost important and widespread social problem. This overview will focus on
      the prevalence of CSA, the associated mental health outcomes, and the preventive
      strategies to prevent CSA from happening in the first place. 

PMID- 23866108
TI  - Genetic engineering of Yarrowia lipolytica for enhanced production of trans-10,
      cis-12 conjugated linoleic acid.
AB  - BACKGROUND: Conjugated linoleic acid (CLA) has been extensively studied for
      decades because of its health benefits including cancer prevention, anti
      atherogenic and anti-obesity effects, and modulation of the immune system. We
      previously described the production of trans-10, cis-12 CLA in Yarrowia
      lipolytica by expressing the gene coding for linoleic acid isomerase from
      Propionibacterium acnes (pai). However the stable strain produced CLA at about
      0.08% of dry cell weight (DCW), a level of production which was not high enough
      for practical applications. The goal of the present study was to enhance
      production of CLA by genetic engineering of Y. lipolytica strains. RESULTS: We
      have now co-expressed the delta 12-desaturase gene (FADS12, d12) from Mortierella
      alpina together with the codon-optimized linoleic acid isomerase (opai) gene in
      Y. lipolytica, expressed under the control of promoter hp16d modified by fusing
      12 copies of UAS1B to the original promoter hp4d. A multi-copy integration
      plasmid was used to further enhance the expression of both genes. Using glucose
      as the sole carbon source, the genetically-modified Y. lipolytica produced trans
      10, cis-12-CLA at a level of up to 10% of total fatty acids and 0.4% of DCW.
      Furthermore, when the recombinant yeast was grown with soybean oil, trans-10, cis
      12-CLA now accumulated at a level of up to 44% of total fatty acids, which
      represented 30% of DCW after 38.5 h of cultivation. In addition, trans-10, cis-12
      CLA was also detected in the growth medium up to 0.9 g/l. CONCLUSIONS: We have
      successfully produced trans-10, cis-12-CLA with a titre of 4 g/l of culture (3.1
      g/l in cells and 0.9 g/l in culture medium). Our results demonstrate the
      potential use of Y. lipolytica as a promising microbial cell factory for trans
      10, cis-12-CLA production.

PMID- 23866109
TI  - Multiple physical symptoms in a military population: a cross-sectional study.
AB  - BACKGROUND: Medically unexplained symptoms have been reported among both
      civilians and military personnel exposed to combat. A large number of military
      personnel deployed to the Gulf War in 1991 reported non-specific symptoms. These
      symptoms did not constitute a clearly defined syndrome. Post-traumatic stress
      disorder (PTSD) and to a lesser degree exposure to combat are associated with
      physical symptoms. METHODS: This is a cross-sectional study of representative
      samples of Sri Lanka Navy Special Forces and regular forces deployed in combat
      areas continuously during a 1-year period. Multiple physical symptoms were
      elicited using a checklist of 53 symptoms. Cases were defined as individuals with
      ten or more symptoms. Symptoms of common mental disorder were identified using
      the General Health Questionnaire 12 (GHQ-12). PTSD was diagnosed using the 17
      item National Centre for PTSD checklist civilian version. RESULTS: Prevalence of
      multiple physical symptoms was 10.4% (95% CI 8.11-12.75). Prevalence was
      significantly less in the Special Forces (5.79%) than in the regular forces
      (13.35%). The mean number of symptoms reported by those who met the criteria for
      PTSD was 12.19 (SD 10.58), GHQ caseness 7.87 (SD 7.57) and those without these
      conditions 2.84 (SD 3.63). After adjusting for socio-demographic and service
      variables, 'thought I might be killed' , 'coming under small arms fire' , and
      'coming under mortar, missile and artillery fire' remained significant. Multiple
      physical symptoms were associated with functional impairment and poor perceived
      general health. CONCLUSIONS: Prevalence of multiple physical symptoms was
      significantly lower in the Special Forces despite high exposure to potentially
      traumatic events. More multiple physical symptoms were reported by personnel with
      PTSD and common mental disorders. Multiple physical symptoms were associated with
      functional impairment.

PMID- 23866110
TI  - Letter to the editor: comments on 'Recovery from chronic fatigue syndrome after
      treatments given in the PACE trial'.

PMID- 23866112
TI  - Letter to the editor: 'Recovery from chronic fatigue syndrome after treatments
      given in the PACE trial': recovery or remission?

PMID- 23866113
TI  - Letter to the editor: 'Recovery from chronic fatigue syndrome after treatments
      given in the PACE trial': an appropriate threshold for a recovery?

PMID- 23866114
TI  - Letter to the editor: 'Recovery from chronic fatigue syndrome after treatments
      given in the PACE trial': data on the recovery groups as a whole would be useful.

PMID- 23866115
TI  - Letter to the editor: comments on 'Recovery from chronic fatigue syndrome after
      treatments given in the PACE trial'.

PMID- 23866116
TI  - Letter to the editor: comments on 'Recovery from chronic fatigue syndrome after
      treatments given in the PACE trial'.

PMID- 23866117
TI  - Letter to the editor: response to correspondence concerning 'recovery from
      chronic fatigue syndrome after treatments in the PACE trial'.

PMID- 23866118
TI  - TNFalpha and IL-17 cooperatively stimulate glucose metabolism and growth factor
      production in human colorectal cancer cells.
AB  - BACKGROUND: Inflammation is a well-known etiological factor for colorectal
      cancer, but mechanisms underlying the linkage between inflammation and cancer are
      incompletely understood. We hypothesized that two pro-inflammatory cytokines,
      TNFalpha and IL-17, might play a role in promoting colorectal carcinogenesis.
      Aerobic glycolysis is a metabolic adaptation that promotes the
      survival/proliferation of cancer cells. Paracrine signaling between tumor cells
      and cancer-associated fibroblasts also plays a role in carcinogenesis. METHODS:
      The effect of TNFalpha and IL-17 on aerobic glycolysis and growth factor
      production in cultured human colorectal cancer cells was investigated. Glucose
      utilization and lactate production were quantified by measuring the disappearance
      of glucose and appearance of lactate in the culture medium. Glucose transporter
      and glycolytic enzyme expression levels were measured by immunoblotting. RESULTS:
      TNFalpha and IL-17 cooperatively stimulated glycolysis in HT-29, T84, Caco-2 and
      HCT116 colorectal cancer cells. Treatment of HT-29 cells with TNFalpha plus IL-17
      also increased the expression of HIF-1alpha and c-myc, two factors know to induce
      the transcription of genes encoding components of the glycolytic pathway. To
      further investigate mechanisms for cytokine-stimulated glycolysis, the effects of
      TNFalpha and IL-17 on expression of six members and one regulator of the
      glycolytic pathway were investigated. TNFalpha and IL-17 cooperatively increased
      the expression of the glucose transporter SLC2A1 and hexokinase-2 but did not
      regulate expression of glucose transporter SLC2A3, enolase-1, pyruvate kinase M2,
      lactate dehydrogenase A, or 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3
      (PFKFB3). Experiments with inhibitors indicated that HIF-1alpha played a role in
      induction of SLC2A1 and that the transcription factor NF-kappaB played a role in
      induction of hexokinase-2 by TNFalpha and IL-17. TNFalpha and IL-17 also
      synergistically stimulated production by HT-29 cells of a growth factor that
      simulated proliferation/survival of NIL8 fibroblastic cells. The activity of this
      factor was not specifically inhibited by the EGFR inhibitor AG1478, indicating
      that it is not an EGFR ligand. CONCLUSIONS: Chronic inflammation is known to
      promote colorectal tumorigenesis. The pro-inflammatory cytokines TNFalpha and IL
      17 may contribute to this effect by stimulating glycolysis and growth factor
      production in colorectal cancer cells.

PMID- 23866119
TI  - Directed funding to address under-provision of treatment for substance use
      disorders: a quantitative study.
AB  - BACKGROUND: Substance use disorders (SUDs) are a substantial problem in the
      United States (U.S.), affecting far more people than receive treatment. This is
      true broadly and within the U.S. military veteran population, which is our focus.
      To increase funding for treatment, the Veterans Health Administration (VA) has
      implemented several initiatives over the past decade to direct funds toward SUD
      treatment, supplementing the unrestricted funds VA medical centers receive. We
      study the 'flypaper effect' or the extent to which these directed funds have
      actually increased SUD treatment spending. METHODS: The study sample included all
      VA facilities and used observational data spanning years 2002 to 2010. Data were
      analyzed with a fixed effects, ordinary least squares specification with
      monetized workload as the dependent variable and funding dedicated to SUD
      specialty clinics the key dependent variable, controlling for unrestricted
      funding. RESULTS: We observed different effects of dedicated SUD specialty clinic
      funding over the period 2002 to 2008 versus 2009 to 2010. In the earlier period,
      there is no evidence of a significant portion of the dedicated funding sticking
      to its target. In the later period, a substantial proportion--38% in 2009 and 61%
      in 2010--of funding dedicated to SUD specialty clinics did translate into
      increased medical center spending for SUD treatment. In comparison, only five
      cents of every dollar of unrestricted funding is spent on SUD treatment.
      CONCLUSIONS: Relative to unrestricted funding, dedicated funding for SUD
      treatment was much more effective in increasing workload, but only in years 2009
      and 2010. The differences in those years relative to prior ones may be due to the
      observed management focus on SUD and SUD-related treatment in the later years. If
      true, this suggests that in a centrally directed healthcare organization such as
      the VA, funding dedicated to a service is a necessary, but not sufficient
      condition for increasing resources expended for that service.

PMID- 23866120
TI  - A longitudinal examination of neuropsychological and clinical functioning in boys
      with attention deficit hyperactivity disorder (ADHD): improvements in executive
      functioning do not explain clinical improvement.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) often, but not
      always, persists into adulthood. Investigations of the associations between
      clinical and biological markers of persistence can shed light on causal pathways.
      It has been proposed that compensatory improvements in executive
      neuropsychological functioning are associated with clinical improvements. This is
      the first study to test this hypothesis prospectively. METHOD: The clinical and
      neuropsychological functioning of 17 boys with ADHD (mean age 10.45 years at time
      1; 14.65 years at time 2) and 17 typically developing (TYP) boys (mean age 10.39
      years at time 1; 14.47 years at time 2) was tested on two occasions, 4 years
      apart. This was done using a battery of standardized neuropsychological tests
      that included tasks with high and low executive demands. RESULTS: Clinical
      improvements were observed over time. Neuropsychological performance improvements
      were also evident, with ADHD boys developing with a similar pattern to TYP boys,
      but with a developmental lag. Whilst there was an association between reduced
      symptoms and superior performance at retest for one task with a high executive
      demand (spatial working memory), this was not seen with two further high
      executive demand tasks [Stockings of Cambridge and intra-dimensional extra
      dimensional (ID/ED) set shifting]. Also, there was no association between change
      in executive functioning and change in symptoms. Baseline performance on the
      ID/ED set-shifting task predicted better clinical outcome. Only change in
      performance on the low executive demand delayed matching-to-sample task predicted
      better clinical outcome. CONCLUSIONS: These data highlight the importance of
      longitudinal measurements of cognition, symptoms and treatment response over time
      in children and adolescents with ADHD.

PMID- 23866121
TI  - Relative hydrophobicity between the phases and partition of cytochrome-c in
      glycine ionic liquids aqueous two-phase systems.
AB  - In this work, glycine ionic liquids tetramethylammonium glycine ([N1111][Gly]),
      tetraethylammonium glycine ([N2222][Gly]), tetra-n-butylammonium glycine
      ([N4444][Gly]), tetra-n-butylphosphonium glycine ([P4444][Gly]) and tetra-n
      pentylammonium glycine ([N5555][Gly]) were synthesized and used to prepare
      aqueous two-phase systems (ATPSs) in the presence of K2HPO4. Binodal curves of
      such ATPSs and partition coefficients of a series of dinitrophenylated (DNP)
      amino acids in these ATPSs were determined at 298.15K to understand the effect of
      cationic structure of the ionic liquids on the phase-forming ability of glycine
      ionic liquids, relative hydrophobicity between the phases in the ionic liquids
      ATPSs, and polarity of the ionic liquids-rich phases. With the attempt to
      correlate the relative hydrophobicity of the phases in the ATPSs with their
      extraction capability for proteins, partition coefficients of cytochrome-c in the
      ATPSs were also determined. It was shown that partition coefficients of
      cytochrome-c were in the range from 2.83 to 20.7 under the studied pH conditions.
      Then, hydrophobic interactions between cytochrome-c and the ionic liquid are
      suggested to be the main driving force for the preferential partition of
      cytochrome-c in the glycine ionic liquid-rich phases of the ATPSs. Result derived
      from polarity of the ionic liquids-rich phases supports this mechanism. 

PMID- 23866122
TI  - Enantiomeric analysis of polycyclic musks in water by chiral gas chromatography
      tandem mass spectrometry.
AB  - Galaxolide (HHCB), tonalide (AHTN), phantolide (AHDI), traseolide (ATII) and
      cashmeran (DPMI) are synthetic polycyclic musks (PCMs). They are all commonly
      used in fragrance industries as racemic mixtures. A sensitive and robust
      enantioselective analytical method was developed to facilitate measurement of
      these chemicals in wastewater and environmental samples. The method is based on
      gas chromatography with tandem mass spectrometry (GC-MS/MS). Enantioseparation
      was assessed using four commercially available chiral capillary columns.
      Optimised resolution was achieved using a dual-column configuration of a chiral
      heptakis(2,3- di-O-methyl-6-O-t-butyl dimethylsilyl)-beta-cyclodextrin column
      combined with a (non-chiral) HP-5MS column. This configuration was demonstrated
      to be capable of effectively resolving all commercially manufactured enantiomers
      of these five PCMs. Method detection limits for single enantiomers in drinking
      water and surface water range between 1.01 and 2.39ngL(-1). Full validation of
      the application of this method in these aqueous matrices is provided. 

PMID- 23866123
TI  - Large-volume sample stacking for in vivo monitoring of trace levels of gamma
      aminobutyric acid, glycine and glutamate in microdialysates of periaqueductal
      gray matter by capillary electrophoresis with contactless conductivity detection.
AB  - A new variant of large-volume sample stacking injection (LVSS) was used in the
      capillary electrophoresis with capacitively coupled contactless conductivity
      detection (CE/C(4)D) determination of the neurotransmitters gamma-aminobutyric
      acid (GABA), glycine (Gly) and glutamate (Glu) in microdialysates of
      periaqueductal gray matter (PAG). The separation capillary was filled to 98% from
      the injection side with a sample of microdialysate in acetonitrile.
      Simultaneously with turning on the separation voltage, the sample zone was forced
      out by the background electrolyte by increasing the pressure in the terminal
      capillary outlet vessel. As a consequence of the stacking effect, the analyte was
      concentrated from the large sample volume into a narrow zone at the
      sample/background electrolyte boundary close to the injection end of the
      capillary. Under these conditions, LOD values of 9, 10 and 15nM were determined
      in the model samples for GABA, Gly and Glu, respectively; RSD equalled 0.5% for
      the migration times and 1.0-1.9% for the peak areas, respectively. In analysis of
      microdialysates of PAG, LOD values of 29, 29 and 37nM were determined for GABA,
      Gly and Glu, respectively; RSD equalled 0.5-0.7% for the migration times and 2.6
      8.2% for the peak areas, respectively. The determined basal levels of the
      neurotransmitters in PAG microdialysates are 0.08, 4.7 and 0.8MUM for GABA, Gly
      and Glu, respectively. Carrageenan-induced hyperalgesia increases the Gly and Glu
      levels and reduces GABA in PAG microdialysate. Peroral administration of
      paracetamol in hyperalgesia effectively reduces the Gly value and has no effect
      on Glu and GABA. 

PMID- 23866124
TI  - Analytical strategies based on chromatography-mass spectrometry for the
      determination of estrogen-mimicking compounds in food.
AB  - Food safety can be compromised by the presence of a wide variety of substances,
      deriving from both natural and anthropogenic sources. Among these substances,
      compounds exhibiting various degrees of estrogenic activity have been widely
      studied in environmental samples, whereas less attention has been devoted to food
      matrices. The aim of the present review is to give a general overview on the
      recent analytical methods based on gas or liquid chromatography coupled to mass
      spectrometry for the determination of estrogen-like compounds in foods, including
      new developments, improvements and upcoming trends in the field. Attention will
      be focused on four representative groups of compounds, i.e. natural and synthetic
      estrogens, mycoestrogens, phytoestrogens, and alkylphenols. 

PMID- 23866125
TI  - Determination of Lewisites and their hydrolysis products in aqueous and
      multiphase samples by in-sorbent tube butyl thiolation followed by thermal
      desorption-gas chromatography-full scan mass spectrometry.
AB  - A rapid, sensitive and robust method for determining the chemical warfare agents
      Lewisites and their hydrolysis products in aqueous and multiphase sample matrices
      has been developed as an extension of the previous work (Terzic, 2010 [32]). In
      the new method, the acidification of the sample and use of 1-butanethiol
      derivatisation instead of trimethylsilylation significantly improved both,
      qualitative and quantitative aspects of targeted analysis of Lewisite species.
      The limit of detection was <=100ng/ml in full scan MS, with sample volume of
      10MUl only. The whole sample preparation procedure took 9min, while the gas
      chromatography (GC)-mass spectrometry (MS) analysis cycle was under 22min. The
      method deals efficiently with the multiphase sample matrices offering a fast and
      simple alternative to the conventional approach of liquid-liquid extraction
      combined with derivatisation. Multiphase sample matrices can be encountered or
      formed when preparing environmental, industrial, waste or decontamination waste
      samples for a GC-MS analysis. The applicability and robustness of the method were
      demonstrated by the successful analysis of 11 years old OPCW Official Proficiency
      Test sample and a triphase liquid sample. The same equipment set-up, tubes and
      derivatising agent have been used for collection, preparation and analysis of
      Lewisites in air samples (Terzic et al., 2012 [35]). The minimal logistic
      requirements, ease of operation, versatility and other features aforementioned,
      make this method an excellent choice for an environmental or forensic field
      laboratory. 

PMID- 23866126
TI  - Roles of singlet oxygen and triplet excited state of dissolved organic matter
      formed by different organic matters in bacteriophage MS2 inactivation.
AB  - Inactivation of bacteriophage MS2 by reactive oxygen species (ROS) and triplet
      excited state of dissolved organic matter ((3)DOM*) produced by irradiation of
      natural and synthetic sensitizers with simulated sunlight of wavelengths greater
      than 320 nm was investigated. Natural sensitizers included purified DOM isolates
      obtained from wastewater and river waters, and water samples collected from
      Singapore River, Stamford Canal, and Marina Bay Reservoir in Singapore. Linear
      correlations were found between MS2 inactivation rate constants (kobs) and the
      photo-induced reaction rate constants of 2,4,6-trimethylphenol (TMP), a probe
      compound shown to react mainly with (3)DOM*. Linear correlations between MS2 kobs
      and singlet oxygen ((1)O2) concentrations were also found for both purified DOM
      isolates and natural water samples. These correlations, along with data from
      quenching experiments and experiments with synthetic sensitizers, Rose Bengal
      (RB), 3'-methoxyacetophenone (3'-MAP), and nitrite [Formula: see text] , suggest
      that (1)O2, (3)DOM*, and hydroxyl radicals ((*)OH) could inactivate bacteriophage
      MS2. Linear correlations between MS2 kobs and Specific Ultraviolet Absorption
      determined at 254 nm (SUVA254) were also found for both purified DOM isolates and
      natural samples. These results suggest the potential use of TMP as a chemical
      probe and SUVA254 as an indicator for virus inactivation in natural and purified
      DOM water samples.

PMID- 23866127
TI  - Breakage and growth towards a stable aerobic granule size during the treatment of
      wastewater.
AB  - To better understand granule growth and breakage processes in aerobic granular
      sludge systems, the particle size of aerobic granules was tracked over 50 days of
      wastewater treatment within four sequencing batch reactors fed with abattoir
      wastewater. These experiments tested a novel hypothesis stating that granules
      equilibrate to a certain stable granule size (the critical size) which is
      determined by the influence of process conditions on the relative rates of
      granule growth and granule breakage or attrition. For granules that are larger
      than the critical size, granule breakage and attrition outweighs granule growth,
      and causes an overall reduction in granule size. For granules at the critical
      size, the overall growth and size reduction processes are balanced, and granule
      size is stable. For granules that are smaller than the critical size, granule
      growth outweighs granule breakage and attrition, and causes an overall increase
      in granule size. The experimental reactors were seeded with mature granules that
      were either small, medium, or large sized, these having respective median granule
      sizes of 425 MUm, 900 MUm and 1125 MUm. An additional reactor was seeded with a
      mixture of the sized granules to represent the original source of the granular
      sludge. The experimental results were analysed together with results of a
      previous granule formation study that used mixed seeding of granules and
      floccular sludge. The analysis supported the critical size hypothesis and showed
      that granules in the reactors did equilibrate towards a common critical size of
      around 600-800 MUm. Accordingly, it is expected that aerobic granular reactors at
      steady-state operation are likely to have granule size distributions around a
      characteristic critical size. Additionally, the results support that maintaining
      a quantity of granules above a particular size is important for granule formation
      during start-up and for process stability of aerobic granule systems. Hence,
      biomass washout needs to be carefully managed to optimize granule formation
      during the reactor start-up.

PMID- 23866128
TI  - Understanding the combined influence of fine sediment and glyphosate herbicide on
      stream periphyton communities.
AB  - Pesticides and deposited fine sediment have independently been associated with
      changes in relative abundance and species richness in aquatic ecosystems, but the
      interplay between these two stressors in agricultural streams is poorly
      understood. A 28-day experiment in outdoor stream mesocosms examined the effects
      of four levels each of fine sediment coverage (0, 25, 75, 100%) and glyphosate
      based herbicide concentration (0, 50, 200, 370 MUg/L) on periphyton communities
      (algae and bacteria) in a fully factorial, repeated-measures design. Our aims
      were to determine whether (i) increased levels of sediment and glyphosate had
      individual and/or additive effects, (ii) increased sediment reduced the toxicity
      of glyphosate (antagonistic multiple stressor interaction), or (iii) sediment
      adsorbed glyphosate prolonged the effects of exposure (synergistic interaction).
      We also assigned all algal taxa to three ecological guilds (low-profile, high
      profile and motile growth forms) and separately determined their responses to the
      treatments. As individual stressors, sediment addition affected all algal
      community-level metrics, whereas glyphosate addition only affected algal
      community evenness. Bacterial taxon richness was unaffected by either stressor.
      In combination, however, significant overall sediment by glyphosate interactions
      were detected, demonstrating synergistic (algal evenness, high-profile and motile
      guilds) or antagonistic effects (low-profile guild). Our experiment underscores
      the importance of considering both structural and functional indicators,
      including algal guild representation, when assessing the mechanisms by which
      periphyton communities respond to multiple stressors.

PMID- 23866129
TI  - Slow sand filters effectively reduce Phytophthora after a pathogen switch from
      Fusarium and a simulated pump failure.
AB  - Slow sand filtration has been shown to effectively reduce Phytophthora zoospores
      in irrigation water. This experiment tested the reduction of Phytophthora colony
      forming units (CFUs) by slow sand filtration systems after switching the pathogen
      contaminating plant leachate from Fusarium to Phytophthora and the resilience of
      the system to a short period without water, as might be caused by a pump failure.
      The slow sand filtration system greatly reduced Phytophthora CFUs and
      transmission after switching the pathogens. In addition, Phytophthora reduction
      by the slow sand filter was equally effective before and after the simulated pump
      failure. Reduction of Fusarium was not seen by the SSFs, before or after the
      simulated pump failure. The results suggest that slow sand filters are effective
      at reducing larger organisms, such as Phytophthora zoospores, even after a pump
      failure or a change in pathogens. 

PMID- 23866130
TI  - Author's responses to the comment by Seong-Hoon Yoon on "A new insight into
      membrane fouling mechanism in submerged membrane bioreactor: osmotic pressure
      during cake layer filtration" published in Water Research, vol. 47, pp. 2777
      2786, 2013.

PMID- 23866131
TI  - Phosphate recovery using hybrid anion exchange: applications to source-separated
      urine and combined wastewater streams.
AB  - There is increasing interest in recovering phosphorus (P) from various wastewater
      streams for beneficial use as fertilizer and to minimize environmental impacts of
      excess P on receiving waters. One such example is P recovery from human urine,
      which has a high concentration of phosphate (200-800 mg P/L) and accounts for a
      small volume (~ 1%) of total wastewater flow. Accordingly, the goal of this study
      was to evaluate the potential to recover P from source-separated and combined
      wastewater streams that included undiluted human urine, urine diluted with tap
      water, greywater, mixture of urine and greywater, anaerobic digester supernatant,
      and secondary wastewater effluent. A hybrid anion exchange (HAIX) resin
      containing hydrous ferric oxide was used to recover P because of its selectivity
      for phosphate and the option to precipitate P minerals in the waste regeneration
      solution. The P recovery potential was fresh urine > hydrolyzed urine > greywater
      > biological wastewater effluent > anaerobic digester supernatant. The maximum
      loading of P on HAIX resin was fresh urine > hydrolyzed urine > anaerobic
      digester supernatant ~ greywater > biological wastewater effluent. Results
      indicated that the sorption capacity of HAIX resin for phosphate and the total P
      recovery potential were greater for source-separated urine than the combined
      wastewater streams of secondary wastewater effluent and anaerobic digester
      supernatant. Dilution of urine with tap water decreased the phosphate loading on
      HAIX resin. The results of this work advance the current understanding of
      nutrient recovery from complex wastewater streams by sorption processes.

PMID- 23866132
TI  - Preliminary trial on degradation of waste activated sludge and simultaneous
      hydrogen production in a newly-developed solar photocatalytic reactor with
      AgX/TiO2-coated glass tubes.
AB  - A solar fluidized tubular photocatalytic reactor (SFTPR) with simple and
      efficient light collector was developed to degrade waste activated sludge (WAS)
      and simultaneously produce hydrogen. The photocatalyst was a TiO2 film doped by
      silver and silver compounds (AgX). The synthesized photocatalyst, AgX/TiO2,
      exhibited higher photocatalytic activity than TiO2 (99.5% and 30.6% of methyl
      orange removal, respectively). The installation of light collector could increase
      light intensity by 26%. For WAS treatment using the SFTPR, 69.1% of chemical
      oxygen demand (COD) removal and 7866.7 MUmol H2/l-sludge of hydrogen production
      were achieved after solar photocatalysis for 72 h. The SFTPR could be a promising
      photocatalysis reactor to effectively degrade WAS with simultaneous hydrogen
      production. The results can also provide a useful base and reference for the
      application of photocatalysis on WAS degradation in practice.

PMID- 23866133
TI  - Evaluating the effectiveness of copper sulphate, chlorine, potassium
      permanganate, hydrogen peroxide and ozone on cyanobacterial cell integrity.
AB  - Cyanobacterial blooms are continuously critical challenges in drinking water
      systems which can have various negative impacts such as production of taste,
      odour and toxic compounds. Furthermore, the intracellular metabolites could be
      released into surrounding waters when the cyanobacterial membranes are destroyed.
      Although a variety of techniques have been developed to control cyanobacterial
      blooms and remove cyanobacterial cells or metabolites in water treatment
      processes, the effect of these treatments on the membrane integrity of
      cyanobacterial cells have not been systematically studied and compared. This
      study evaluated the effectiveness of copper sulphate (CuSO4), chlorine, potassium
      permanganate (KMnO4), hydrogen peroxide (H2O2) and ozone on the cell integrity
      and densities of Microcystis aeruginosa. All of these technologies can compromise
      the cell membrane of cyanobacteria to varying degrees. Chlorine showed the
      strongest ability to impair the cell integrity with a majority (>= 88%) of the
      cells compromised within the first minute and with the cell lysis rates ranging
      of 0.640-3.82 h(-1) during 1-60 min. Ozone dose of 6 mg L(-1) also could induce
      90% lysis of the cyanobacterial cells in 5 min and the cell lysis rate of KMnO4
      (10 mg L(-1)) was 0.829 h(-1). CuSO4 and H2O2 could not only destroy the
      viability of cyanobacterial cells but also showed algistatic potential over the 7
      day treatment. The potential of all the oxidants (chlorine, KMnO4, H2O2 and
      ozone) considered as algicides were discussed in this study. The benefits and
      drawbacks of these control and water treatment options were assessed as well.

PMID- 23866134
TI  - The use of hybrid constructed wetlands for wastewater treatment with special
      attention to nitrogen removal: a review of a recent development.
AB  - The hybrid systems were developed in the 1960s but their use increased only
      during the late 1990 s and in the 2000s mostly because of more stringent
      discharge limits for nitrogen and also more complex wastewaters treated in
      constructed wetlands (CWs). The early hybrid CWs consisted of several stages of
      vertical flow (VF) followed by several stages of horizontal flow (HF) beds.
      During the 1990 s, HF-VF and VF-HF hybrid systems were introduced. However, to
      achieve higher removal of total nitrogen or to treat more complex industrial and
      agricultural wastewaters other types of hybrid constructed wetlands including
      free water surface (FWS) CWs and multistage CWs have recently been used as well.
      The survey of 60 hybrid constructed wetlands from 24 countries reported after
      2003 revealed that hybrid constructed wetlands are primarily used on Europe and
      in Asia while in other continents their use is limited. The most commonly used
      hybrid system is a VF-HF constructed wetland which has been used for treatment of
      both sewage and industrial wastewaters. On the other hand, the use of a HF-VF
      system has been reported only for treatment of municipal sewage. Out of 60
      surveyed hybrid systems, 38 have been designed to treat municipal sewage while 22
      hybrid systems were designed to treat various industrial and agricultural
      wastewaters. The more detailed analysis revealed that VF-HF hybrid constructed
      wetlands are slightly more efficient in ammonia removal than hybrid systems with
      FWS CWs, HF-VF systems or multistage VF and HF hybrid CWs. All types of hybrid
      CWs are comparable with single VF CWs in terms of NH4-N removal rates. On the
      other hand, CWs with FWS units remove substantially more total nitrogen as
      compared to other types of hybrid constructed wetlands. However, all types of
      hybrid constructed wetlands are more efficient in total nitrogen removal than
      single HF or VF constructed wetlands.

PMID- 23866135
TI  - Critical assessment of extracellular polymeric substances extraction methods from
      mixed culture biomass.
AB  - Extracellular polymeric substances (EPS) have a presumed determinant role in the
      structure, architecture, strength, filterability, and settling behaviour of
      microbial solids in biological wastewater treatment processes. Consequently,
      numerous EPS extraction protocols have recently been published that aim to
      optimize the trade off between high EPS recovery and low cell lysis. Despite
      extensive efforts, the obtained results are often contradictory, even when
      analysing similar biomass samples and using similar experimental conditions,
      which greatly complicates the selection of an extraction protocol. This study
      presents a rigorous and critical assessment of existing physical and chemical EPS
      extraction methods applied to mixed-culture biomass samples (nitrifying,
      nitritation-anammox, and activated sludge biomass). A novel fluorescence-based
      method was developed and calibrated to quantify the lysis potential of different
      EPS extraction protocols. We concluded that commonly used methods to assess cell
      lysis (DNA concentrations or G6PDH activities in EPS extracts) do not correlate
      with cell viability. Furthermore, we discovered that the presence of certain
      chemicals in EPS extracts results in severe underestimation of protein and
      carbohydrate concentrations by using standard analytical methods. Keeping both
      maximum EPS extraction yields and minimal biomass lysis as criteria, it was
      identified a sonication-based extraction method as the best to determine and
      compare tightly-bound EPS fractions in different biomass samples. Protein was
      consistently the main EPS component in all analysed samples. However, EPS from
      nitrifying enrichments was richer in DNA, the activated sludge EPS had a higher
      content in humic acids and carbohydrates, and the nitritation-anammox EPS, while
      similar in composition to the nitrifier EPS, had a lower fraction of hydrophobic
      biopolymers. In general, the easily-extractable EPS fraction was more abundant in
      carbohydrates and humic substances, while DNA could only be found in tightly
      bound EPS fractions. In conclusion, the methodology presented herein supports the
      rational selection of analytical tools and EPS extraction protocols in further
      EPS characterization studies. 

PMID- 23866136
TI  - Effect of microwave hydrolysis on transformation of steroidal hormones during
      anaerobic digestion of municipal sludge cake.
AB  - Fate and removal of 16 steroidal (estrogenic, androgenic and progestogenic)
      hormones were studied during advanced anaerobic digestion of sludge cake using
      microwave (MW) pretreatment. Effect of pretreatment temperature (80, 120, 160 
      degrees C), operating temperature (mesophilic at 35 +/- 2  degrees C,
      thermophilic at 55 +/- 2  degrees C) and sludge retention time (SRT: 20, 10, 5
      days) were studied employing eight lab-scale semi-continuously fed digesters. To
      determine the potential effect of MW hydrolysis, hormones were quantified in
      total (sorbed + soluble) and supernatant (soluble) phases of the digester
      influent and effluent streams. Seven of 16 hormones were above the method
      reporting limit (RL) in one or more of the samples. Hormone concentrations in
      total phase of un-pretreated (control) and pretreated digester feeds ranged in
      <157-2491 ng/L and <157-749 ng/L, respectively. The three studied factors were
      found to be statistically significant (95% confidence level) in removal of one or
      more hormones from soluble and/or total phase. MW hydrolysis of the influent
      resulted in both release (from sludge matrix) and attenuation of hormones in the
      soluble phase. Accumulation of estrone (E1) as well as progesterone (Pr) and
      androstenedione (Ad) in most of the digesters indicated possible microbial
      transformations among the hormones. Compared to controls, all pretreated
      digesters had lower total hormone concentrations in their influent streams. At 20
      days SRT, highest total removal (E1+E2+Ad +Pr) was observed for the thermophilic
      control digester (56%), followed by pretreated mesophilic digesters at 120 
      degrees C and 160  degrees C with around 48% efficiency. In terms of conventional
      performance parameters, relative (to control) improvements of MW pretreated
      digesters at a 5-d SRT ranged in 98-163% and 57-121%, for volatile solids removal
      and methane production, respectively.

PMID- 23866137
TI  - Reinvestigation on the ozonation of N-nitrosodimethylamine: Influencing factors
      and degradation mechanism.
AB  - N-nitrosodimethylamine (NDMA), as a new disinfection byproduct, is a potential
      carcinogen. In this study, we focused on the role of ozone in NDMA degradation.
      We characterized the removal efficiency, influencing factors and degradation
      mechanism. Our results demonstrated that ozonation was an efficient process for
      NDMA degradation. The removal efficiency was affected by initial NDMA
      concentration; higher NDMA dosing required higher ozone utilization. NDMA
      oxidation was favored at high ozone dosage and high pH. NDMA ozonation under
      various pH as well as hydroxyl radical (OH) inhibition experiments verified that
      OH generated from ozone dominated NDMA oxidation. The main products of NDMA
      ozonation were methylamine (MA), dimethylamine (DMA), nitromethane (NM) and
      ammonium (AM). Their yields changed with the amount of ozone provided. A NDMA
      ozonation mechanism was proposed. It is suggested that NDMA degradation is
      induced by OH attacking through any of four pathways, with oxygen involving in
      the oxidation process. MA generation was due to OH attacking on amine nitrogen
      and methyl group. DMA formation was related to OH attacking on nitrosyl nitrogen
      via a parallel pathway. We speculate that supersaturated dissolved oxygen by
      ozone decomposition is responsible for NM generation by further oxidation of MA
      and DMA. AM formation may be favored due to MA degradation under OH exposure. 

PMID- 23866138
TI  - Investigating why recycling gravity harvested algae increases harvestability and
      productivity in high rate algal ponds.
AB  - It has previously been shown that recycling gravity harvested algae promotes
      Pediastrum boryanum dominance and improves harvestability and biomass production
      in pilot-scale High Rate Algal Ponds (HRAPs) treating domestic wastewater. In
      order to confirm the reproducibility of these findings and investigate the
      mechanisms responsible, this study utilized twelve 20 L outdoor HRAP mesocosms
      operated with and without algal recycling. It then compared the recycling of
      separated solid and liquid components of the harvested biomass against un
      separated biomass. The work confirmed that algal recycling promoted P. boryanum
      dominance, improved 1 h-settleability by >20% and increased biomass productivity
      by >25% compared with controls that had no recycling. With regard to the improved
      harvestability, of particular interest was that recycling the liquid fraction
      alone caused a similar improvement in settleability as recycling the solid
      fraction. This may be due to the presence of extracellular polymeric substances
      in the liquid fraction. While there are many possible mechanisms that could
      account for the increased productivity with algal recycling, all but two were
      systematically eliminated: (i) the mean cell residence time was extended thereby
      increasing the algal concentration and more fully utilizing the incident sunlight
      and, (ii) the relative proportions of algal growth stages (which have different
      specific growth rates) was changed, resulting in a net increase in the overall
      growth rate of the culture.

PMID- 23866139
TI  - A dynamic and complex monochloramine stress response in Escherichia coli revealed
      by transcriptome analysis.
AB  - Despite the widespread use of monochloramine in drinking water treatment, there
      is surprisingly little information about its mode of action. In this study, DNA
      microarrays were used to investigate the global gene expression of Escherichia
      coli cells exposed to sub-lethal concentrations of monochloramine, with a focus
      on temporal dynamics. Genes induced by monochloramine were associated with
      several stress response functions, including oxidative stress, DNA repair,
      multidrug efflux, biofilm formation, antibiotic resistance, and cell wall repair.
      The diversity of functional associations supports a model of monochloramine
      action involving multiple cellular targets including cell membranes, nucleic
      acids, and proteins. These data suggest that E. coli responds to monochloramine
      exposure by activating diverse defense responses rather than a single antioxidant
      system and the exposure may also induce biofilm formation. The induction of
      multidrug efflux pumps and specific antibiotic resistance genes further suggests
      that exposure to monochloramine may contribute to reduced susceptibility to some
      antibiotics. 

PMID- 23866140
TI  - Comparing microbial water quality in an intermittent and continuous piped water
      supply.
AB  - Supplying piped water intermittently is a common practice throughout the world
      that increases the risk of microbial contamination through multiple mechanisms.
      Converting an intermittent supply to a continuous supply has the potential to
      improve the quality of water delivered to consumers. To understand the effects of
      this upgrade on water quality, we tested samples from reservoirs, consumer taps,
      and drinking water provided by households (e.g. from storage containers) from an
      intermittent and continuous supply in Hubli-Dharwad, India, over one year. Water
      samples were tested for total coliform, Escherichia coli, turbidity, free
      chlorine, and combined chlorine. While water quality was similar at service
      reservoirs supplying the continuous and intermittent sections of the network,
      indicator bacteria were detected more frequently and at higher concentrations in
      samples from taps supplied intermittently compared to those supplied continuously
      (p < 0.01). Detection of E. coli was rare in continuous supply, with 0.7% of tap
      samples positive compared to 31.7% of intermittent water supply tap samples
      positive for E. coli. In samples from both continuously and intermittently
      supplied taps, higher concentrations of total coliform were measured after
      rainfall events. While source water quality declined slightly during the rainy
      season, only tap water from intermittent supply had significantly more indicator
      bacteria throughout the rainy season compared to the dry season. Drinking water
      samples provided by households in both continuous and intermittent supplies had
      higher concentrations of indicator bacteria than samples collected directly from
      taps. Most households with continuous supply continued to store water for
      drinking, resulting in re-contamination, which may reduce the benefits to water
      quality of converting to continuous supply.

PMID- 23866141
TI  - High occurrence of hepatitis E virus in samples from wastewater treatment plants
      in Switzerland and comparison with other enteric viruses.
AB  - Hepatitis E virus (HEV) is responsible for many enterically transmitted viral
      hepatitides around the world. It is currently one of the waterborne diseases of
      global concern. In industrialized countries, HEV appears to be more common than
      previously thought, even if it is rarely virulent. In Switzerland, seroprevalence
      studies revealed that HEV is endemic, but no information was available on its
      environmental spread. The aim of this study was to investigate -using qPCR- the
      occurrence and concentration of HEV and three other viruses (norovirus genogroup
      II, human adenovirus-40 and porcine adenovirus) in influents and effluents of 31
      wastewater treatment plants (WWTPs) in Switzerland. Low concentrations of HEV
      were detected in 40 out of 124 WWTP influent samples, showing that HEV is
      commonly present in this region. The frequency of HEV occurrence was higher in
      summer than in winter. No HEV was detected in WWTP effluent samples, which
      indicates a low risk of environmental contamination. HEV occurrence and
      concentrations were lower than those of norovirus and adenovirus. The
      autochthonous HEV genotype 3 was found in all positive samples, but a strain of
      the non-endemic and highly pathogenic HEV genotype I was isolated in one sample,
      highlighting the possibility of environmental circulation of this genotype. A
      porcine fecal marker (porcine adenovirus) was not detected in HEV positive
      samples, indicating that swine are not the direct source of HEV present in
      wastewater. Further investigations will be necessary to determine the reservoirs
      and the routes of dissemination of HEV.

PMID- 23866142
TI  - Drinking water and biofilm disinfection by Fenton-like reaction.
AB  - A Fenton-like disinfection process was conducted with Fenton's reagent (H2O2) at
      pH 3 or 5 on autochthonous drinking water biofilms grown on corroded or non
      corroded pipe material. The biofilm disinfection by Fenton-like oxidation was
      limited by the low content of iron and copper in the biomass grown on non
      corroded plumbing. It was slightly improved by spiking the distribution system
      with some additional iron source (soluble iron II or ferrihydrite particles
      appeared as interesting candidates). However successful in situ disinfection of
      biofilms was only achieved in fully corroded cast iron pipes using H2O2 and
      adjusting the pH to 5. These new results provide additional support for the use
      of Fenton's processes for cleaning drinking water distribution systems
      contaminated with biological agents or organics. 

PMID- 23866143
TI  - Influence of biogeochemical interactions on metal bioleaching performance in
      contaminated marine sediment.
AB  - Bioleaching strategies are still far from finding real applications in sediment
      clean-up, although metabolic mechanisms governing bioleaching processes have been
      deeply studied and can be considered well established. In this study, we carried
      out bioleaching experiments, using autotrophic and heterotrophic acidophilic
      bacteria strains, and worked with marine sediments characterized by different
      geochemical properties and metal concentrations and speciations. The
      solubilization efficiency of the metals was highly variable, with the highest for
      Zn (40%-76%) and the lowest for Pb (0%-7%). Our data suggest that the role of
      autotrophic Fe/S oxidizing bacteria is mainly associated with the production and
      re-cycling of leaching chemical species, mainly as protons and ferric ions. Metal
      solubilization appears to be more related to establishing environmental
      conditions that allow each metal or semimetal to remain stable in the solution
      phase. Thus, the maintenance of acid and oxidative conditions, the chemical
      behavior in aqueous environment of each metal species and the geochemical
      characteristics of sediment interact intimately to influence metal solubilization
      in site-specific and metal-specific way. 

PMID- 23866144
TI  - Degradation of pharmaceuticals in non-sterile urban wastewater by Trametes
      versicolor in a fluidized bed bioreactor.
AB  - The constant detection of pharmaceuticals (PhACs) in the environment demonstrates
      the inefficiency of conventional wastewater treatment plants to completely remove
      them from wastewaters. So far, many studies have shown the feasibility of using
      white rot fungi to remove these contaminants. However, none of them have studied
      the degradation of several PhACs in real urban wastewater under non-sterile
      conditions, where mixtures of contaminants presents at low concentrations (ng L(
      1) to MUg L(-1)) as well as other active microorganisms are present. In this
      work, a batch fluidized bed bioreactor was used to study, for the first time, the
      degradation of PhACs present in urban wastewaters at their pre-existent
      concentrations under non-sterile conditions. Glucose and ammonium tartrate were
      continuously supplied as carbon and nitrogen source, respectively, and pH was
      maintained at 4.5. Complete removal of 7 out of the 10 initially detected PhACs
      was achieved in non-sterile treatment, while only 2 were partially removed and 1
      of the PhACs analyzed increased its concentration. In addition, Microtox test
      showed an important reduction of toxicity in the wastewater after the treatment.

PMID- 23866145
TI  - Chlorination of bromide-containing waters: enhanced bromate formation in the
      presence of synthetic metal oxides and deposits formed in drinking water
      distribution systems.
AB  - Bromate formation from the reaction between chlorine and bromide in homogeneous
      solution is a slow process. The present study investigated metal oxides enhanced
      bromate formation during chlorination of bromide-containing waters. Selected
      metal oxides enhanced the decay of hypobromous acid (HOBr), a requisite
      intermediate during the oxidation of bromide to bromate, via (i)
      disproportionation to bromate in the presence of nickel oxide (NiO) and cupric
      oxide (CuO), (ii) oxidation of a metal to a higher valence state in the presence
      of cuprous oxide (Cu2O) and (iii) oxygen formation by NiO and CuO. Goethite
      (alpha-FeOOH) did not enhance either of these pathways. Non-charged species of
      metal oxides seem to be responsible for the catalytic disproportionation which
      shows its highest rate in the pH range near the pKa of HOBr. Due to the ability
      to catalyze HOBr disproportionation, bromate was formed during chlorination of
      bromide-containing waters in the presence of CuO and NiO, whereas no bromate was
      detected in the presence of Cu2O and alpha-FeOOH for analogous conditions. The
      inhibition ability of coexisting anions on bromate formation at pH 8.6 follows
      the sequence of phosphate >> sulfate > bicarbonate/carbonate. A black deposit in
      a water pipe harvested from a drinking water distribution system exerted
      significant residual oxidant decay and bromate formation during chlorination of
      bromide-containing waters. Energy dispersive spectroscopy (EDS) analyses showed
      that the black deposit contained copper (14%, atomic percentage) and nickel
      (1.8%, atomic percentage). Cupric oxide was further confirmed by X-ray
      diffraction (XRD). These results indicate that bromate formation may be of
      concern during chlorination of bromide-containing waters in distribution systems
      containing CuO and/or NiO.

PMID- 23866146
TI  - Photo-Fenton-like treatment of BPA: effect of UV light source and water matrix on
      toxicity and transformation products.
AB  - UV-A (near-UV), UV-C (short-UV) and visible-light assisted Fenton-like treatment
      of Bisphenol A (BPA) was investigated in pure water and raw freshwater samples
      spiked with BPA. Treatment performances were evaluated in terms of BPA
      degradation, dissolved organic carbon (DOC) removal and H2O2 consumption rates.
      Complete BPA degradation accompanied with significant DOC removal was achieved
      for all studied processes. Increasing the initial solution pH only exhibited a
      negative effect on treatment efficiencies when bicarbonate alkalinity was used
      for pH adjustment, whereas the raw freshwater matrix and irradiation type also
      influenced oxidation rates appreciably. Acute toxicity analysis employing Vibrio
      fischeri revealed that the inhibitory effect of BPA decreased significantly
      during the course of Photo-Fenton-like treatment. Several transformation products
      could be identified via HPLC and GC-MS analyses including hydroxylated phenolic
      compounds (hydroquinone; 2-methoxy, 1-4-benzenediol; 4-isopropenylphenol; 4'
      hydroxy-acetophenone; 1-(4-cyclohexylphenyl) ethanone; 4-isopropylenecatechol; 4
      4'-dihydroxybenzophenone; 4-ethyl,1,3-benzenediol), as well as the ring opening
      products hexanoic acid methyl ester, fumaric, succinic and oxalic acids. A
      reaction pathway featuring hydroxylation, dimerization and ring opening steps is
      proposed.

PMID- 23866147
TI  - Efficacy of reactive mineral-based sorbents for phosphate, bacteria, nitrogen and
      TOC removal--column experiment in recirculation batch mode.
AB  - Two mineral-based materials (Polonite and Sorbulite) intended for filter wells in
      on-site wastewater treatment were compared in terms of removal of phosphate (PO4
      P), total inorganic nitrogen (TIN), total organic carbon (TOC) and faecal
      indicator bacteria (Escherichia coli and Enterococci). Using an innovative,
      recirculating system, septic tank effluent was pumped at a hydraulic loading rate
      of 3000 L m(2) d(-1) into triplicate bench-scale columns of each material over a
      90-day period. The results showed that Polonite performed better with respect to
      removal of PO4-P, retaining on average 80% compared with 75% in Sorbulite. This
      difference was attributed to higher CaO content in Polonite and its faster
      dissolution. Polonite also performed better in terms of removal of bacteria
      because of its higher pH value. The total average reduction in E. coli was 60% in
      Polonite and 45% in Sorbulite, while for Enterococci the corresponding value was
      56% in Polonite and 34% in Sorbulite. Sorbulite removed TIN more effectively,
      with a removal rate of 23%, while Polonite removed 11% of TIN, as well as TOC.
      Organic matter (measured as TOC) was accumulated in the filter materials but was
      also released periodically. The results showed that Sorbulite could meet the
      demand in removing phosphate and nitrogen with reduced microbial release from the
      wastewater treatment process.

PMID- 23866148
TI  - Comparison of NOM removal and microbial properties in up-flow/down-flow BAC
      filter.
AB  - The removal of natural organic matter (NOM) in term of CODMn by up-flow
      biologically activated carbon filter (UBACF) and down-flow biologically activated
      carbon filter (DBACF) was investigated in a pilot-scale test. The impacts of the
      molecular weight distribution of NOM on its degradation by the UBACF and DBACF
      were evaluated. The relationship between biodegradation and the microbial
      properties in the UBACF and DBACF were approached as well. The feed water of the
      UBACF and DBACF were pumped from the effluent of the rapid sand filtration (RSF)
      of Chengnan Drinking Water Treatment Plant (CDWTP), Huaian, Jiangsu Province,
      China. When the adsorption was the dominant mechanism of NOM removal at the
      initial stage of operation, the CODMn removal efficiency by the UBACF was lower
      than the DBACF. However, with the microbes gradually accumulated and biofilm
      formed, the removal of CODMn by the UBACF increased correspondingly to 25.3%, at
      the steady-state operation and was approximately 10% higher than that by the
      DBACF. Heterotrophy plate count (HPC) in the finished water of the UBACF was
      observed 30% higher than that of the DBACF. The UBACF effluent had higher
      concentration of detached bacteria whereas the DBACF harbored more attached
      biomass. The highest attached biomass concentration of the UBACF was found in the
      middle of the GAC bed. On the contrary, the highest attached biomass
      concentration of the DBACF was found on the top of the GAC bed. Furthermore, a
      total of 9479 reads by pyrosequencing was obtained from samples of the UBACF and
      DBACF effluents. The UBACF effluent had a more diverse microbial community and
      more even distribution of species than the DBACF effluent did.
      Alphaproteobacteria and Betaproteobacteria were the dominant groups in the
      finished water of the UBACF and DBACF. The higher organic matter removal by the
      UBACF was attributed to the presence of its higher biologically activity.

PMID- 23866149
TI  - Trace organic solutes in closed-loop forward osmosis applications: influence of
      membrane fouling and modeling of solute build-up.
AB  - In this study, trace organics transport in closed-loop forward osmosis (FO)
      systems was assessed. The FO systems considered, consisted of an FO unit and a
      nanofiltration (NF) or reverse osmosis (RO) unit, with the draw solution
      circulating between both units. The rejection of trace organics by FO, NF and RO
      was tested. It was found that the rejection rates of FO were generally comparable
      with NF and lower than RO rejection rates. To assess the influence of fouling in
      FO on trace organics rejection, FO membranes were fouled with sodium alginate,
      bovine serum albumin or by biofilm growth, after which trace organics rejection
      was tested. A negative influence of fouling on FO rejection was found which was
      limited in most cases, while it was significant for some compounds such as
      paracetamol and naproxen, indicating specific compound-foulant interactions. The
      transport mechanism of trace organics in FO was tested, in order to differentiate
      between diffusive and convective transport. The concentration of trace organics
      in the final product water and the build-up of trace organics in the draw
      solution were modeled assuming the draw solution was reconcentrated by NF/RO and
      taking into account different transport mechanisms for the FO membrane and
      different rejection rates by NF/RO. Modeling results showed that if the FO
      rejection rate is lower than the RO rejection rate (as is the case for most
      compounds tested), the added value of the FO-RO cycle compared to RO only at
      steady-state was small for diffusively and negative for convectively transported
      trace organics. Modeling also showed that trace organics accumulate in the draw
      solution.

PMID- 23866150
TI  - Predicting aqueous solubility of environmentally relevant compounds from
      molecular features: a simple but highly effective four-dimensional model based on
      Project to Latent Structures.
AB  - The aqueous solubility (log S) of xenobiotic chemicals has been identified as a
      key characteristic in determining their bioaccessibility/bioavailability and
      their fate and transport in aquatic environments. We here explore and evaluate
      the use of a state-of-the-art data analysis technique (Project to Latent
      Structures, PLS) to estimate log S of environmentally relevant chemicals. A large
      number (n = 624) of molecular descriptors was computed for over 1400 organic
      chemicals, and then refined by a feature selection technique. Candidate predictor
      descriptors were fitted to data by means of PLS, which was optimized by an
      internal leave-one-out cross-validation technique and validated by an external
      data set. The final (best) PLS model with only four variables (AlogP, X1sol, Mv,
      and E) exhibited noteworthy stability and good predictive power. It was able to
      explain 91% of the data (n = 1400) variance with an average absolute error of 0.5
      log units through the solubilities span over 12 orders of magnitude. The newly
      proposed model is transparent, easily portable from one user to another, and
      robust enough to accurately estimate log S of a wide range of emerging
      contaminants.

PMID- 23866151
TI  - Occurrence of seven artificial sweeteners in the aquatic environment and
      precipitation of Tianjin, China.
AB  - Seventy water samples, including wastewaters, tap waters, fresh surface waters,
      coastal waters, groundwaters, and precipitation samples, from Tianjin, China,
      were analyzed for seven commonly used artificial sweeteners (ASs). The
      concentrations of the investigated ASs were generally in the order of wastewater
      treatment plant (WWTP) influent > WWTP effluent > surface water > tap water >
      groundwater ~ precipitation, while the composition profiles of ASs varied in
      different waters. Acesulfame, sucralose, cyclamate, and saccharin were
      consistently detected in surface waters and ranged from 50 ng/L to 0.12 mg/L,
      while acesulfame was the dominant AS in surface and tap waters. Aspartame was
      found in all of the surface waters at a concentration up to 0.21 MUg/L, but was
      not found in groundwaters and tap waters. Neotame and neohesperidin
      dihydrochalcone were less frequently detected and the concentrations were low.
      The concentrations of the ASs in some of the surface waters were of the same
      order with those in the WWTP influents, but not with the effluents, indicating
      there are probably untreated discharges into the surface waters. The ASs were
      detected in precipitation samples with high frequency, and acesulfame, saccharin,
      and cyclamate were the predominant ASs, with concentrations ranging from 3.5 ng/L
      to 1.3 MUg/L. A gross estimation revealed that precipitation may act as a source
      for saccharin and cyclamate in the surface environment of Tianjin city. Moreover,
      the presence of ASs in the atmosphere was primarily assessed by taking 4 air
      samples to evaluate their potential source in precipitation.

PMID- 23866152
TI  - Roles of extracellular polymeric substances (EPS) in the migration and removal of
      sulfamethazine in activated sludge system.
AB  - The occurrences, transformation of antibiotics in biological wastewater treatment
      plants have attracted increasing interests. However, roles of extracellular
      polymeric substances (EPS) of activated sludge on the fate of antibiotics are not
      clear. In this study, the roles of EPS in the migration and removal of one
      typical antibiotic, sulfamethazine (SMZ), in activated sludge process were
      investigated. The interaction between EPS and SMZ was explored through a combined
      use of fluorescence spectral analysis, laser light scattering and
      microcalorimetry techniques. Results show that SMZ interacted with the proteins
      in EPS mainly with a binding constant of 1.91 * 10(5) L/mol. The binding process
      proceeded spontaneously, and the driving force was mainly from the hydrophobic
      interaction. After binding, the structure of EPS was expanded and became loose,
      which favored the mass transfer and pollution capture. The removal of SMZ was
      influenced by interaction with EPS. SMZ could be effectively adsorbed on EPS,
      which accounted for up to 61.8% of total SMZ adsorbed by sludge at the initial
      adsorption stage and declined to around 35.3% at the subsequent biodegradation
      stage. The enrichment of SMZ by EPS was beneficial for SMZ removal and
      acquisition by microbes at the subsequent biodegradation stage.

PMID- 23866153
TI  - Conductive heating and microwave hydrolysis under identical heating profiles for
      advanced anaerobic digestion of municipal sludge.
AB  - Microwave (2.45 GHz, 1200 W) and conventional heating (custom pressure vessel)
      pretreatments were applied to dewatered municipal waste sludge (18% total solids)
      using identical heating profiles that span a wide range of temperatures (80-160 
      degrees C). Fourteen lab-scale semi-continuous digesters were set up to optimize
      the energy (methane) output and sludge retention time (SRT) requirements of
      untreated (control) and thermally pretreated anaerobic digesters operated under
      mesophilic and thermophilic temperatures. Both pretreatment methods indicated
      that in the pretreatment range of 80-160  degrees C, temperature was a
      statistically significant factor (p-value < 0.05) for increasing solubilization
      of chemical oxygen demand and biopolymers (proteins, sugars, humic acids) of the
      waste sludge. However, the type of pretreatment method, i.e. microwave versus
      conventional heating, had no statistically significant effect (p-value >0.05) on
      sludge solubilization. With the exception of the control digesters at a 5-d SRT,
      all control and pretreated digesters achieved steady state at all three SRTs,
      corresponding to volumetric organic loading rates of 1.74-6.96 g chemical oxygen
      demand/L/d. At an SRT of 5 d, both mesophilic and thermophilic controls stopped
      producing biogas after 20 d of operation with total volatile fatty acids
      concentrations exceeding 1818 mg/L at pH <5.64 for mesophilic and 2853 mg/L at pH
      <7.02 for thermophilic controls, while the pretreated digesters continued
      producing biogas. Furthermore, relative (to control) organic removal efficiencies
      dramatically increased as SRT was shortened from 20 to 10 and then 5 d,
      indicating that the control digesters were challenged as the organic loading rate
      was increased. Energy analysis showed that, at an elevated temperature of 160 
      degrees C, the amount of methane recovered was not enough to compensate for the
      energy input. Among the digesters with positive net energy productions, control
      and pretreated digesters at 80  degrees C were more favorable at an SRT of 10 d.

PMID- 23866154
TI  - Bioanalytical and chemical assessment of the disinfection by-product formation
      potential: role of organic matter.
AB  - Disinfection by-products (DBP) formed from natural organic matter and
      disinfectants like chlorine and chloramine may cause adverse health effects.
      Here, we evaluate how the quantity and quality of natural organic matter and
      other precursors influence the formation of DBPs during chlorination and
      chloramination using a comprehensive approach including chemical analysis of
      regulated and emerging DBPs, total organic halogen quantification, organic matter
      characterisation and bioanalytical tools. In vitro bioassays allow us to assess
      the hazard potential of DBPs early in the chain of cellular events, when the DBPs
      react with their molecular target(s) and activate stress response and defence
      mechanisms. Given the reactive properties of known DBPs, a suite of bioassays
      targeting reactive modes of toxic action including genotoxicity and sensitive
      early warning endpoints such as protein damage and oxidative stress were
      evaluated in addition to cytotoxicity. Coagulated surface water was collected
      from three different drinking water treatment plants, along with reverse osmosis
      permeate from a desalination plant, and DBP formation potential was assessed
      after chlorination and chloramination. While effects were low or below the limit
      of detection before disinfection, the observed effects and DBP levels increased
      after disinfection and were generally higher after chlorination than after
      chloramination, indicating that chlorination forms higher concentrations of DBPs
      or more potent DBPs in the studied waters. Bacterial cytotoxicity, assessed using
      the bioluminescence inhibition assay, and induction of the oxidative stress
      response were the most sensitive endpoints, followed by genotoxicity. Source
      waters with higher dissolved organic carbon levels induced increased DBP
      formation and caused greater effects in the endpoints related to DNA damage
      repair, glutathione conjugation/protein damage and the Nrf2 oxidative stress
      response pathway after disinfection. Fractionation studies indicated that all
      molecular weight fractions of organic carbon contributed to the DBP formation
      potential, with the humic rich fractions forming the greatest amount of DBPs,
      while the low molecular weight fractions formed more brominated DBPs due to the
      high bromide to organic carbon ratio. The presence of higher bromide
      concentrations also led to a higher fraction of brominated DBPs as well as
      proportionally higher effects. This study demonstrates how a suite of analytical
      and bioanalytical tools can be used to effectively characterise the precursors
      and formation potential of DBPs.

PMID- 23866155
TI  - Oral health of visually impaired schoolchildren in Khartoum State, Sudan.
AB  - BACKGROUND: Although oral health care is a vital component of overall health, it
      remains one of the greatest unattended needs among the disabled. The aim of this
      study was to assess the oral health status and oral health-related quality of
      life (Child-OIDP in 11-13-year-old) of the visually challenged school attendants
      in Khartoum State, the Sudan. METHODS: A school-based survey was conducted in Al
      Nour institute [boys (66.3%), boarders (35.9%), and children with partial visual
      impairment (PVI) (44.6%)]. Two calibrated dentists examined the participants
      (n=79) using DMFT/dmft, Simplified Oral Hygiene Index (OHI-S), dental care index,
      and traumatic dental injuries (TDI) index. Oral health related quality of life (C
      OIDP) was administered to 82 schoolchildren. RESULTS: Caries experience was
      46.8%. Mean DMFT (age>=12, n=33) was 0.4 +/- 0.7 (SiC 1.6), mean dmft (age<12,
      n=46) was 1.9 +/-2.8 (SiC 3.4), mean OHIS 1.3 +/- 0.9. Care Index was zero. One
      fifth of the children suffered TDI (19%). Almost one third (29%) of the 11-13
      year old children reported an oral impact on their daily performances. A quarter
      of the schoolchildren (25.3%) required an urgent treatment need. Analysis showed
      that children with partial visual impairment (PVI) were 6.3 times (adjusted) more
      likely to be diagnosed with caries compared to children with complete visual
      impairment (CVI), and children with caries experience were 1.3 times (unadjusted)
      more likely to report an oral health related impact on quality of life.
      CONCLUSIONS: Visually impaired schoolchildren are burdened with oral health
      problems, especially caries. Furthermore, the 11-13 year olds' burden with caries
      showed a significant impact on their quality of life.

PMID- 23866156
TI  - Decreased hydration status of emergency department physicians and nurses by the
      end of their shift.
AB  - BACKGROUND: Typical emergency department (ED) shifts are physically demanding.
      The aim of this study was to assess the hydration status of ED physicians and
      nurses by the end of their shifts. METHODS: A prospective cross-sectional
      clinical study of ED physicians and nurses assessing fluid intake, activities,
      vital signs, weight, urine specific gravity and ketones at the end of the shift.
      Forty-three participants were tested over 172 shifts distributed over 48% in the
      morning, 20% in the evening and 32% at night. Fifty-eight percent were females,
      and 51% were physicians. RESULTS: Overall, participants lost 0.3% of their body
      weight by the end of the shift. While physicians lost a mean of 0.57 kg (+/- SD
      0.28; P < 0.0001, 95% CI 0.16-0.28), nurses lost 0.12 kg (+/- SD 0.25; P <
      0.0001, 95% CI 0.07-1.7). While nurses drank more fluid (P < 0.0001), physicians
      had a higher specific gravity of 1.025 (P < 0.01), visited the washroom less
      often (P < 0.0001) and reported less workload and stress (P = 0.01 and 0.008,
      respectively). There were no major changes in vital signs or urinary ketones
      (OR.0.41, 95% CI 0.1-2.1). In a multivariate analysis, being male (OR 13.5, 95%
      CI 1.6-112.5), being of younger age (OR 4.1, 95% CI 1.7-10.2), being Middle
      Eastern (OR 5.3, 95% CI 1.1-26.2), working the morning shift (OR 2.7, 95% CI 0.7
      10.5) and having less fluid intake (OR 5.7, 95% CI 1.2-26.6) were significant
      predictors of decreased hydration. CONCLUSIONS: The majority of physicians and to
      a lesser extent nurses working in a tertiary care emergency department have
      decreased hydration status at the end of the shift. Therefore, awareness of the
      hydration status by emergency department staff is needed. A further study in a
      similar setting with more subjects and a better balance among the variables is
      recommended.

PMID- 23866157
TI  - Emodin induces apoptosis of human cervical cancer hela cells via intrinsic
      mitochondrial and extrinsic death receptor pathway.
AB  - BACKGROUND: Emodin is a natural anthraquinone derivative isolated from the Rheum
      palmatum L. AIM: The aim of the present study was to investigate the effect of
      emodin on the apoptosis of the human cervical cancer line HeLa and to identify
      the mechanisms involved. METHODS: Relative cell viability was assessed by MTT
      assay after treatment with emodin. Cell apoptosis was detected with TUNEL,
      Hoechst 33342 staining and quantified with flow cytometry using annexin FITC-PI
      staining. RESULTS: The percentage of apoptotic cells was 0.8, 8.2, 22.1, and
      43.7%, respectively. The mRNA levels of Caspase-9, -8 and -3 detected by Real
      time PCR after treatment with emodin were significantly increased. Emodin
      increased the protein levels of Cytochome c, Apaf-1, Fas, FasL, and FADD but
      decreased the protein levels of Pro-caspase-9, Pro-caspase-8 and Pro-caspase-3.
      CONCLUSION: We conclude that the emodin inhibited HeLa proliferation by inducing
      apoptosis through the intrinsic mitochondrial and extrinsic death receptor
      pathways.

PMID- 23866158
TI  - Solifenacin-induced delirium and hallucinations.
AB  - Solifenacin-induced cognitive adverse effects have not been reported frequently,
      but solifenacin-induced delirium and hallucinations with successful switching to
      darifenacin, without additional drug, have not been reported in the literature.
      In this case report, we present an 80-year-old Caucasian male with insomnia and
      anxiety symptoms and overactive bladder who developed delirium and hallucinations
      when treated with solifenacin and trazodone. After solifenacin discontinuation
      and switching to darifenacin, symptoms significantly improved immediately. Such a
      case has not yet been described in literature; however, an adverse effect
      associated with solifenacin can occur, as this report clearly demonstrates. 

PMID- 23866159
TI  - Prevalence of hyperuricemia and its related risk factors in healthy adults from
      Northern and Northeastern Chinese provinces.
AB  - BACKGROUND: Hyperuricemia (HUA) is a potential risk factor for developing insulin
      resistance, hypertension, dyslipidemia and cardiovascular disease. Therefore, we
      studied the prevalence of HUA and associated risk factors in the population of
      two provinces in northern China. METHODS: Based on the research of Chinese
      Physiological Constant and Health Conditions conducted in 2008-2010, we enrolled
      29,639 subjects in a randomized, stratified study in four sampling areas in
      Heilongjiang Province and the Inner Mongolia Autonomous Region. We collected
      13,140 serum samples to determine biochemical indicators including uric acid(UA),
      glucose, blood lipids, liver function, and renal function, and finally a
      representative sample of 8439 aged 18 years and older was determined. We also
      defined and stratified HUA, hypertension, diabetes, obesity and lipid
      abnormalities according to international guidelines. RESULTS: There were
      significant differences in the UA levels between different genders and regions.
      The total prevalence of HUA is 13.7%. Men had a higher prevalence of HUA than
      women (21% vs. 7.9%; P < 0.0001). As age increased, HUA prevalence decreased in
      men but rose in women. The suburbs of big cities had the highest HUA prevalence
      (18.7%), and in high-prevalence areas the proportion of women with HUA also
      increased. A stepwise logistic regression model was used to filter out twelve HUA
      risk factors, including age, gender, residence, hypercholesterolemia,
      hypertriglyceridemia, impaired fasting glucose, hypertension, obesity, abdominal
      obesity, CKD, drinking and sleeping. After adjusting for these factors, the odds
      ratio of HUA was 1.92 times higher in men than in women. Compared with
      agricultural and pastoral areas, the odds ratio of having HUA was 2.14 for
      participants in the suburbs of big cities and 1.57 in the center of big cities.
      CONCLUSIONS: The prevalence of HUA is high in northern China. The differences in
      HUA prevalence by geographic region suggested that unbalanced economic
      development and health education, therefore HUA prevention measures should be
      strengthened to improve quality of life and reduce health care costs.

PMID- 23866160
TI  - Quantifying cognitive reserve in older adults by decomposing episodic memory
      variance: replication and extension.
AB  - The theory of cognitive reserve attempts to explain why some individuals are more
      resilient to age-related brain pathology. Efforts to explore reserve have been
      hindered by measurement difficulties. Reed et al. (2010) proposed quantifying
      reserve as residual variance in episodic memory performance that remains after
      accounting for demographic factors and brain pathology (whole brain, hippocampal,
      and white matter hyperintensity volumes). This residual variance represents the
      discrepancy between an individual's predicted and actual memory performance. The
      goals of the present study were to extend these methods to a larger, community
      based sample and to investigate whether the residual reserve variable is
      explained by age, predicts longitudinal changes in language, and predicts
      dementia conversion independent of age. Results support this operational measure
      of reserve. The residual reserve variable was associated with higher reading
      ability, lower likelihood of meeting criteria for mild cognitive impairment,
      lower odds of dementia conversion in dependent of age, and less decline in
      language abilities over 3 years. Finally, the residual reserve variable moderated
      the negative impact of memory variance explained by brain pathology on language
      decline. This method has the potential to facilitate research on the mechanisms
      of cognitive reserve and the efficacy of interventions designed to impart
      reserve.

PMID- 23866161
TI  - Chronic cerebrospinal venous insufficiency is not associated with cognitive
      impairment in multiple sclerosis.
AB  - BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been reported
      in multiple sclerosis (MS) yet its significance in relation to cognitive function
      is undetermined.This study measured the association between the presence and
      severity of CCSVI and cognitive impairment in patients with MS. METHODS: CCSVI
      was assessed using extra-cranial and trans-cranial Doppler sonography in 109 MS
      patients (79 with relapsing-remitting, 23 with secondary-progressive and 7 with
      primary-progressive disease subtype). A subject was considered CCSVI-positive if
      >=2 venous hemodynamic criteria were fulfilled. The Minimal Assessment of
      Cognitive Function in MS (MACFIMS) battery was administered assessing the full
      spectrum of cognitive domains known to be affected by MS. Depression was
      quantified using the Beck Depression Inventory Fast Screen (BDIFS). Partial
      correlations, analysis of variance (or covariance) and linear regression were
      used to examine the hypothesis that CCSVI status is related to cognition or
      depression after controlling for education and gender. RESULTS: There were 64
      (58.7%) patients who were considered CCSVI-positive. The regression models
      predicting venous hemodynamic insufficiency severity score were not statistically
      significant for any of the MACFIMS predictor variables. The analysis of variance
      tests showed a significant effect of CCSVI-positive diagnosis on cognitive
      ability in only one of the 10 MACFIMS outcomes, and that one was in the opposite
      direction of the tested hypothesis. There was no correspondence between CCSVI
      diagnosis and depression, as measured by the BDIFS. CONCLUSIONS: We find no
      evidence of an association between the presence and severity of CCSVI with
      cognitive impairment and depression in patients with MS.

PMID- 23866162
TI  - Improving quality of cause-of-death reporting in New York City.

PMID- 23866163
TI  - Factors predicting physical activity among children with special needs.
AB  - INTRODUCTION: Obesity is especially prevalent among children with special needs.
      Both lack of physical activity and unhealthful eating are major contributing
      factors. The objective of our study was to investigate barriers to physical
      activity among these children. METHODS: We surveyed parents of the 171 children
      attending Vista Del Mar School in Los Angeles, a nonprofit school serving a
      socioeconomically diverse group of children with special needs from kindergarten
      through 12th grade. Parents were asked about their child's and their own physical
      activity habits, barriers to their child's exercise, and demographics. The
      response rate was 67%. Multivariate logistic regression was used to examine
      predictors of children being physically active at least 3 hours per week.
      RESULTS: Parents reported that 45% of the children were diagnosed with attention
      deficit hyperactivity disorder, 38% with autism, and 34% with learning
      disabilities; 47% of children and 56% of parents were physically active less than
      3 hours per week. The top barriers to physical activity were reported as child's
      lack of interest (43%), lack of developmentally appropriate programs (33%), too
      many behavioral problems (32%), and parents' lack of time (29%). However, child's
      lack of interest was the only parent-reported barrier independently associated
      with children's physical activity. Meanwhile, children whose parents were
      physically active at least 3 hours per week were 4.2 times as likely to be
      physically active as children whose parents were less physically active (P =
      .01). CONCLUSION: In this group of students with special needs, children's
      physical activity was strongly associated with parental physical activity; parent
      reported barriers may have had less direct effect. Further studies should examine
      the importance of parental physical activity among children with special needs.

PMID- 23866164
TI  - Formative evaluation for a healthy corner store initiative in Pitt County, North
      Carolina: engaging stakeholders for a healthy corner store initiative, part 2.
AB  - INTRODUCTION: We examined the feasibility of increasing access to healthful food
      in corner stores to inform a Communities Putting Prevention to Work (CPPW)
      initiative by engaging stakeholders (corner store owners and customers) in a
      formative evaluation. METHODS: Qualitative interviews were conducted with corner
      store owners and managers (n = 11). Customer intercept surveys (n = 179) were
      also conducted with customers of 9 stores. Corner stores were located in rural
      food deserts (municipalities without a chain supermarket) and in low-income,
      urban municipalities in eastern North Carolina. Interviews were transcribed
      verbatim and double-coded. Qualitative themes related to feasibility of
      increasing access to healthful foods were extracted. Shopping patterns of rural
      and urban customers were compared by using t tests. RESULTS: Corner store owners
      were willing to stock more healthful foods, but they perceived that customer
      demand for these foods was low. Rural customers reported more frequently shopping
      at corner stores than urban customers and more frequently stated that the reason
      they do not eat more fruits and vegetables is that the stores in which they shop
      do not sell them. Most customers reported they would be very or somewhat likely
      to purchase fresh produce at a corner store. CONCLUSION: Corner stores may be an
      important source of food for rural and low-income residents and thus a good place
      in which to intervene. The results of this formative evaluation were used to plan
      and evaluate a CPPW healthy corner store initiative.

PMID- 23866166
TI  - Improving public health agency and system performance: fortification for
      promoting population health and wellness.

PMID- 23866165
TI  - Formative evaluation for a healthy corner store initiative in Pitt County, North
      Carolina: assessing the rural food environment, part 1.
AB  - INTRODUCTION: Obesity prevalence in the rural United States is higher than in
      urban or suburban areas, perhaps as a result of the food environment. Because
      rural residents live farther from supermarkets than their urban- and suburban
      dwelling counterparts, they may be more reliant on smaller corner stores that
      offer fewer healthful food items. METHODS: As part of a Communities Putting
      Prevention to Work (CPPW) healthy corner store initiative, we reviewed audit
      tools in the fall of 2010 to measure the consumer food environment in eastern
      North Carolina and chose the NEMS-S-Rev (Nutrition Environment Measures Survey
      Stores-Revised) to assess 42 food stores. During the spring and summer of 2011, 2
      trained graduate assistants audited stores, achieving interrater reliability of
      at least 80%. NEMS-S-Rev scores of stores in rural versus urban areas were
      compared. RESULTS: Overall, healthful foods were less available and of lower
      quality in rural areas than in urban areas. NEMS-S-Rev scores indicated that
      healthful foods were more likely to be available and had similar pricing and
      quality in rural corner stores than in urban corner stores. CONCLUSION: Food
      store audit data provided a baseline to implement and evaluate a CPPW healthy
      corner store initiative in Pitt County. This work serves as a case study,
      providing lessons learned for engaging community partners when conducting rural
      food store audits.

PMID- 23866167
TI  - Determinants of pregnancy and induced and spontaneous abortion in a jointly
      determined framework: evidence from a country-wide, district-level household
      survey in India.
AB  - This study provides evidence on the principal determinants of pregnancy and
      abortion in India using a large country-wide district-level data set (DLHS 2007).
      The paper provides an economic framework for the analysis of pregnancy and
      abortion. The study distinguishes between induced and spontaneous abortion and
      compares the effects of their determinants. The results show that there are wide
      differences between induced and spontaneous abortions in terms of the sign and
      magnitude of the estimated effects of several of their determinants, most notably
      wealth, the woman's age and her desire for children. The study makes a
      methodological contribution by proposing a trivariate probit estimation framework
      that recognizes the joint dependence of pregnancy and induced and spontaneous
      abortion, and provides evidence in support of this joint dependence. The study
      reports an inverted U-shaped effect of a woman's age on her pregnancy and both
      forms of abortion. The turning point in each case is quite robust to the
      estimation framework. A significant effect of contextual variables, at the
      village level, constructed from the individual responses, on a woman's pregnancy
      is found. The effects are weaker in the case of induced abortion, and
      insignificant in the case of spontaneous abortion. The results are shown to be
      fairly robust. This paper extends the literature on the relation between son
      preference and fertility by examining the link between mother's son preference
      and desire for more children with abortion rates.

PMID- 23866168
TI  - Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with
      polycystic ovarian syndrome.
AB  - BACKGROUND: Injecting estradiol valerate (EV) to pre-pubertal or adult female rat
      results in effects similar to those observed in women with polycystic ovarian
      syndrome (PCOS). One of the mechanisms involved in PCOS development is the
      hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the
      unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of
      the innervated ovary. This suggests that, in addition to the sympathetic
      innervation, other neural mechanisms are involved in the development/maintenance
      of PCOS. The aims of present study were analyze if the vagus nerve is one of the
      neural pathways participating in PCOS development. METHODS: Ten-day old rats were
      injected with EV dissolved in corn oil. At 24-days of age sham-surgery,
      unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed
      on these rats. The animals were sacrificed at 90-92 days of age, when they
      presented vaginal estrous preceded by a pro-estrus smear. RESULTS: In EV-induced
      PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries.
      Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or
      bilateral vagotomy were lower than in control rats. CONCLUSIONS: This result
      suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway
      participating in maintaining PCOS. The vagus nerve innervates the ovaries
      directly and indirectly through its synapsis in the celiac-superior-mesenteric
      ganglion, where the somas of neurons originating in the SON are located. Then, it
      is possible that vagotomy effects in EV-induced PCOS rats may be explained as a
      lack of communication between the central nervous system and the ovaries.

PMID- 23866169
TI  - Response to Weiss HR, Moramarco M: "indication for surgical treatment in patients
      with adolescent idiopathic scoliosis - a critical appraisal" (Patient Saf. Surg.
      2013, 7:17).

PMID- 23866171
TI  - Evaluation of recycling the effluent of hydrogen fermentation for biobutanol
      production: kinetic study with butyrate and sucrose concentrations.
AB  - Butyrate in the effluent of hydrogen-producing bioreactor is a potential feed for
      biobutanol production. For recycling butyrate, this study investigated the
      kinetics of biobutanol production by Clostridium beijerinckii NRRL B592 from
      different paired concentrations of butyrate and sucrose in a series of batch
      reactors. Results show that the lag time of butanol production increased with
      higher concentration of either sucrose or butyrate. In regression analyses, the
      maximum specific butanol production potential of 6.49 g g(-1) of dry cell was
      projected for 31.9 g L(-1) sucrose and 1.3 g L(-1) butyrate, and the maximum
      specific butanol production rate of 0.87 g d(-1) g(-1) of dry cell was predicted
      for 25.0 g L(-1) sucrose and 2.6 g L(-1) butyrate. The specific butanol
      production potential will decrease if more butyrate is added to the reactor.
      However, both sucrose and butyrate concentrations are weighted equally on the
      specific butanol production rate. This observation also is true on butanol yield.
      The maximum butanol yield of 0.49 mol mol(-1) was projected for 25.0 g L(-1)
      sucrose and 2.3 g L(-1) butyrate. In addition, a confirmation study found butanol
      yield increased from 0.2 to 0.3 mol mol(-1) when butyrate addition increased from
      0 to 1 g L(-1) under low sugar concentration (3.8 g L(-1) sucrose). The existence
      of butyrate increases the activity of biobutanol production and reduces the
      fermentable sugar concentration needed for acetone-butanol-ethanol fermentation.

PMID- 23866170
TI  - "Money talks, bullshit walks" interrogating notions of consumption and survival
      sex among young women engaging in transactional sex in post-apartheid South
      Africa: a qualitative enquiry.
AB  - BACKGROUND: Transactional sex is believed to be a significant driver of the HIV
      epidemic among young women in South Africa. This sexual risk behaviour is
      commonly associated with age mixing, concurrency and unsafe sex. It is often
      described as a survival- or consumption-driven behaviour. South Africa's history
      of political oppression as well as the globalization-related economic policies
      adopted post-apartheid, are suggested as the underlying contexts within which
      high risk behaviours occur among Black populations. What remains unclear is how
      these factors combine to affect the particular ways in which transactional sex is
      used to negotiate life among young Black women in the country.In this paper we
      explore the drivers of transactional sex among young women aged 16-24, who reside
      in a peri-urban community in South Africa. We also interrogate prevailing
      constructions of the risk behaviour in the context of modernity, widespread
      availability of commodities, and wealth inequalities in the country. METHODS:
      Data were collected through 5 focus group discussions and 6 individual interviews
      amongst young women, men, and community members of various age groups in a
      township in the Western Cape, South Africa. FINDINGS: Young women engaged in
      transactional sex to meet various needs: some related to survival and others to
      consumption. In this poverty-stricken community, factors that created a high
      demand for transactional sex among young women included the pursuit of
      fashionable images, popular culture, the increased availability of commodities,
      widespread use of global technologies, poverty and wealth inequalities.
      Transactional sex encounters were characterized by sexual risk, a casual attitude
      towards HIV, and male dominance. However, the risk behaviour also allowed women
      opportunities to adopt new social roles as benefactors in sexual relationships
      with younger men. CONCLUSION: Transactional sex allows poor, young women to
      access what young people in many parts of the world also prioritize: fashionable
      clothing and opportunities for inclusion in popular youth culture. In the context
      of high HIV prevalence in South Africa, strategies are needed that present young
      women with safer economic gateways to create and consume alternative symbols of
      modernity and social inclusion.

PMID- 23866172
TI  - Quantitative structure-activity relationship to predict acute fish toxicity of
      organic solvents.
AB  - REACH regulation requires ecotoxicological data to characterize industrial
      chemicals. To limit in vivo testing, Quantitative Structure-Activity
      Relationships (QSARs) are advocated to predict toxicity of a molecule. In this
      context, the topic of this work was to develop a reliable QSAR explaining the
      experimental acute toxicity of organic solvents for fish trophic level. Toxicity
      was expressed as log(LC50), the concentration in mmol.L(-1) producing the 50%
      death of fish. The 141 chemically heterogeneous solvents of the dataset were
      described by physico-chemical descriptors and quantum theoretical parameters
      calculated via Density Functional Theory. The best subsets of solvent descriptors
      for LC50 prediction were chosen both through the Kubinyi function associated with
      Enhanced Replacement Method and a stepwise forward multiple linear regressions.
      The 4-parameters selected in the model were the octanol-water partition
      coefficient, LUMO energy, dielectric constant and surface tension. The predictive
      power and robustness of the QSAR developed were assessed by internal and external
      validations. Several techniques for training sets selection were evaluated: a
      random selection, a LC50-based selection, a balanced selection in terms of toxic
      and non-toxic solvents, a solvent profile-based selection with a space filling
      technique and a D-optimality onions-based selection. A comparison with fish LC50
      predicted by ECOSAR model validated for neutral organics confirmed the interest
      of the QSAR developed for the prediction of organic solvent aquatic toxicity
      regardless of the mechanism of toxic action involved. 

PMID- 23866173
TI  - Monitoring of environmental contaminants in raw bovine milk and estimates of
      dietary intakes of children in South Korea.
AB  - Persistent organic pollutants (POPs) are ubiquitous residual contaminants in the
      environment and in the food chain. Milk is an important matrix for monitoring POP
      contamination. This study determined the concentrations of POPs including
      polybrominated diphenyl ethers (PBDEs), hexachlorobenzene (HCB), polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated
      biphenyls (DL-PCBs) in raw bovine milk, and the data was used to estimate dietary
      intakes in South Korea. The average concentrations of PBDEs, HCB, PCDD/Fs, and DL
      PCBs in raw milk were 0.29 ng g(-1)fat, 0.50 ng g(-1)fat, 0.27 pg TEQ g(-1)fat,
      and 0.33 pg TEQ g(-1)fat, respectively. No significant relationship was found
      between the concentrations of analytes and the regions sampled. The dietary
      intakes of PBDEs from the consumption of milk was calculated to be 0.26, 0.10,
      and 0.05ng kg(-1)bwd(-1) for the group of ages 0-6, 7-12, and 13-19,
      respectively. The dietary intakes of HCB was calculated to be 0.44, 0.16, and
      0.09 ng kg(-1)bwd(-1) for the group of ages 0-6, 7-12, and 13-19, respectively.
      The dietary intakes of PCDD/Fs and DL-PCBs was calculated to be 0.78, 0.29, and
      0.16pgTEQ kg(-1)bwd(-1) for the group of ages 0-6, 7-12, and 13-19, respectively.
      These results indicated that the residual levels of PBDEs, HCB, PCDD/Fs, and DL
      PCBs in raw bovine milk were within safe levels.

PMID- 23866174
TI  - Enhancement of phosphorus sorption onto light expanded clay aggregates by means
      of aluminum and iron oxide coatings.
AB  - Phosphorus (P) loading from non-point or point sources increases the
      eutrophication risk of natural waters. The functioning of constructed wetlands
      (CWs) used as natural water treatment systems can be improved by means of
      additional materials adsorbing soluble P. In this study, light expanded clay
      aggregates (LECA) and LECA coated with aluminum (Al) oxide (Al-LECA) or iron (Fe)
      oxide (Fe-LECA) were tested for their efficiency as P sorbents in the pH range 3
      8. The oxide coatings duplicated the actual sorption capacity calculated from the
      sorption isotherms at the P concentration in the equilibrium solution of 20 MUg
      L(-1), assumed to be the allowable P level in purified water. In the oxide-coated
      LECAs the sorption was fast and followed both the first- and second-order
      Lagergren kinetic models, suggesting that the formation of a binuclear surface
      complex was feasible. In LECA, sorption was markedly slower and followed the
      first-order kinetic model, indicating that retention occurred through a
      monodentate attachment. These findings were in harmony with the degree of P
      saturation (DPS) of the sorbent surfaces at the highest P addition level (200 MUg
      L(-1)), DPS being decisively higher for LECA than for the oxide-coated sorbents.
      Accordingly, at higher pH values the competition by hydroxyl ions diminished the
      sorption in LECA relatively more than that in the coated sorbents. In agreement
      with the acidity of Al(3+) being 100 times lower than that of Fe(3+), at elevated
      pH the sorption by Al-LECA proved to be less reversible than that by Fe-LECA. The
      results provide evidence that in CWs Al-coated sorbents are superior to Fe-coated
      ones that are also redox-sensitive and may lose their sorption properties in
      anoxic conditions.

PMID- 23866175
TI  - Effects of 4-nonylphenol on hepatic gene expression of peroxisome proliferator
      activated receptors and cytochrome P450 isoforms (CYP1A1 and CYP3A4) in juvenile
      sole (Solea solea).
AB  - The objective of the present study was to investigate the modulatory effects of
      the xenoestrogen 4-nonylphenol (4-NP) on hepatic peroxisome proliferator
      activated receptor (PPAR) alpha and beta gene expression patterns in relation to
      the detoxification pathways mediated by cytochrome P450 isoforms (CYP1A1 and
      CYP3A4). Waterborne 4-NP-induced effects were compared with those of 10(-8)M
      17beta-estradiol (E2) by using in vivo dose-response experiments carried out with
      juvenile sole (Solea solea). Compared to the controls, significantly higher
      levels of PPARalpha mRNAs were found in fish treated with E2 or 4-NP (10(-6)M) 3
      d after exposure; the highest dose of 4-NP also caused up-regulation of retinoid
      X receptor alpha (RXRalpha) transcript levels. On the contrary, PPARbeta gene
      expression was not modulated by E2 or 4-NP. Our data show that 4-NP-induced
      PPARalpha mRNA levels coincide with suppression of CYP1A1 and CYP3A4 expression
      similarly to E2. The results from these in vivo studies suggest the presence of
      cross-talk between nuclear receptor-mediated signaling pathways and PPARalpha
      that may result in modulation of CYP450 isoforms expression following 4-NP
      treatment in sole liver.

PMID- 23866177
TI  - Management of vascular access in transcatheter aortic valve replacement: part 1:
      basic anatomy, imaging, sheaths, wires, and access routes.
AB  - Transcatheter aortic valve implantation (TAVI) has emerged as a new therapy for
      patients with severe aortic stenosis who are inoperable or at very high risk of
      open heart surgery. Vascular complications are a potential limitation of TAVI and
      have been associated with bleeding, transfusions, and mortality. Transfemoral
      TAVI can be considered the least invasive approach and is therefore the most
      widely used access for TAVI. With the current 18-F to 24-F sheaths, the majority
      of patients can be treated via the transfemoral route. Initially, open surgical
      access was routinely used to introduce the large sheaths and catheters.
      Subsequently, percutaneous techniques have emerged as the new standard, resulting
      in a less invasive, fully percutaneous procedure. Stiff wires allow insertion of
      the sheath and delivery of the device without causing trauma to the artery. Given
      the high burden of vascular disease in TAVI candidates, increasing the
      effectiveness of pre-procedural screening is key. This often begins with
      conventional angiography, but computed tomography allows visualization of the
      artery in 3 dimensions, thereby overcoming some of the limitations of
      conventional angiography. Approximately one third of patients do not have
      adequate anatomy to allow safe transfemoral access. In such patients, alternative
      access routes such as the transapical, transaxillary, or direct aortic access are
      preferred. These alternative routes all have specific advantages and
      disadvantages. 

PMID- 23866176
TI  - The methods and outcomes of cultural adaptations of psychological treatments for
      depressive disorders: a systematic review.
AB  - BACKGROUND: Cultural adaptations of evidence-based psychological treatments (PTs)
      are important to enhance their universal applicability. The aim of this study was
      to review systematically the literature on adaptations of PTs for depressive
      disorders for ethnic minorities in Western countries and for any population in
      non-Western countries to describe the process, extent and nature of the
      adaptations and the effectiveness of the adapted treatments. METHOD: Controlled
      trials were identified using database searches, key informants, previous reviews
      and reference lists. Data on the process and details of the adaptations were
      analyzed using qualitative methods and meta-analysis was used to assess treatment
      effectiveness. RESULTS: Twenty studies were included in this review, of which 16
      were included in the meta-analysis. The process of adaptation was reported in two
      thirds of the studies. Most adaptations were found in the dimensions of language,
      context and therapist delivering the treatment. The meta-analysis revealed a
      statistically significant benefit in favor of the adapted treatment [standardized
      mean difference (SMD) -0.72, 95% confidence interval (CI) -0.94 to -0.49].
      CONCLUSIONS: Cultural adaptations of PTs follow a systematic procedure and lead
      primarily to adaptations in the implementation of the treatments rather than
      their content. Such PTs are effective in the treatment of depressive disorders in
      populations other than those for whom they were originally developed.

PMID- 23866178
TI  - Comparison of 5-year outcomes in patients with and without unprotected left main
      coronary artery disease after treatment with sirolimus-eluting stents: insights
      from the j-Cypher registry.
AB  - OBJECTIVES: This study assessed 5-year outcomes after implantation of sirolimus
      eluting stents (SES) for unprotected left main coronary artery (ULMCA) disease in
      comparison with that for non-left main disease. BACKGROUND: More information on
      long-term outcomes after ULMCA stenting is needed. METHODS: The j-Cypher is a
      multicenter prospective registry of consecutive patients undergoing SES
      implantation in Japan. RESULTS: Among 12,812 patients enrolled in the j-Cypher
      registry, the unadjusted mortality rate at 5 years was significantly higher in
      patients with ULMCA stenting than in patients without ULMCA stenting (22.8% vs.
      14.1%; p < 0.0001); however, the risk for death with ULMCA stenting was no longer
      significant after adjusting for confounders (hazard ratio: 1.18, 95% confidence
      interval: 0.95 to 1.46; p = 0.14). In the lesion-level comparison, the
      nonbifurcation ULMCA lesions treated exclusively with SES had a significantly
      lower rate of target lesion revascularization (TLR) than those in non-ULMCA
      nonbifurcation lesions (2.4% vs. 12.7%; p = 0.04). Among bifurcation lesions,
      those treated with a provisional 2-stent approach had similar rates of TLR (12.1%
      vs. 11.4%; p = 0.79) between the ULMCA and non-ULMCA groups. Lesions treated with
      an elective 2-stent approach had higher TLR rates in the ULMCA group as compared
      with the non-ULMCA group (33.5% vs. 19.7%; p = 0.002). CONCLUSIONS: The safety of
      ULMCA stenting relative to non-LMCA stenting was maintained through 5 years
      follow-up. In terms of efficacy, SES implantation in nonbifurcation ULMCA lesions
      was associated with an extremely low cumulative incidence of TLR, whereas the
      elective 2-stent approach for ULMCA bifurcation lesions was associated with a
      markedly higher cumulative incidence of TLR as compared with that for non-ULMCA
      bifurcation lesions.

PMID- 23866179
TI  - Angiographic outcomes in the PLATO Trial (Platelet Inhibition and Patient
      Outcomes).
AB  - OBJECTIVES: The PLATO (Platelet Inhibition and Patient Outcomes) angiographic
      substudy sought to compare the efficacy of ticagrelor versus clopidogrel with
      respect to angiographic outcomes before and after PCI in the setting of acute
      coronary syndrome. BACKGROUND: Greater platelet inhibition has been associated
      with improved angiographic outcomes before and after percutaneous coronary
      intervention (PCI). Therefore, it was hypothesized that treatment with
      ticagrelor, which achieves more rapid, higher, and more consistent platelet
      inhibition, would be associated with improved angiographic outcomes when compared
      with those of clopidogrel treatment. METHODS: The angiographic cohort consists of
      2,616 patients drawn from the 18,624-patient PLATO trial. Clopidogrel naive or
      pre-treated patients were randomized to 180 mg of ticagrelor or 300 mg of
      clopidogrel (75 mg for clopidogrel pre-treated patients). PCI patients were
      administered, as per treatment group: 1) an additional 90 mg of ticagrelor if >24
      h following the initial loading dose; or 2) an optional further 300 mg of
      clopidogrel or placebo (total 600 mg) prior to PCI. The substudy primary endpoint
      was the incidence of post-PCI TIMI (Thrombolysis In Myocardial Infarction)
      myocardial perfusion grade 3 (TMPG 3) among patients who received a study drug
      prior to PCI. RESULTS: In total, 21.3% of patients were pretreated with
      clopidogrel prior to randomization. There was a short time interval between
      randomization and PCI (median: 0.68 [interquartile range (IQR): 0.30 to 2.21] h)
      among all patients. Post-PCI TMPG 3 was similar between the ticagrelor and
      clopidogrel groups (47.1% vs. 46.9%; p = 0.96). Likewise, the following pre-PCI
      outcomes were similar in the ticagrelor and clopidogrel groups, respectively:
      TMPG 3 (30.5% vs. 31.2%), TIMI flow grade 3 (37.1% vs. 39.3%), corrected TIMI
      frame count (median: 100 vs. 71 frames), TIMI thrombus grade 0 (24.1% vs. 27.6%),
      minimum lumen diameter (median: 0.3 [IQR: 0.0 to 0.6] vs. 0.3 [IQR: 0.0 to 0.6]
      mm) and percentage of diameter stenosis (median: 89 [IQR: 78 to 100] vs. 89 [IQR:
      77 to 100]). CONCLUSIONS: Neither coronary flow nor myocardial perfusion,
      evaluated on coronary angiograms performed before or following PCI procedures
      within a few hours after the start of oral antiplatelet treatment in the setting
      of acute coronary syndromes, demonstrated a difference with ticagrelor versus
      clopidogrel. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients
      With Acute Coronary Syndrome [PLATO]; NCT00391872).

PMID- 23866180
TI  - P2Y12 Receptor Blockade and Myocardial Perfusion.

PMID- 23866181
TI  - The complexity of stenting in bifurcation coronary lesions.

PMID- 23866182
TI  - Radial primary angioplasty: the gold standard treatment for STEMI patients.

PMID- 23866183
TI  - Prognostic significance of bleeding location and severity among patients with
      acute coronary syndromes.
AB  - OBJECTIVES: This study sought to determine if there is an association between
      bleed location and clinical outcomes in acute coronary syndromes (ACS) patients.
      BACKGROUND: The prognostic significance of bleeding location among ACS patients
      undergoing cardiac catheterization is not well known. METHODS: We analyzed in
      hospital bleeding events among 9,978 patients randomized in the SYNERGY (Superior
      Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein
      IIb/IIIa Inhibitors) study. Bleeding events were categorized by location as
      access site, systemic, surgical, or superficial, and severity was graded using
      the GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries)
      definition. We assessed the association of each bleeding location and severity
      with 6-month risk of death or myocardial infarction using a multicovariate
      adjusted Cox proportional hazard model. RESULTS: A total of 4,900 bleeding events
      were identified among 3,694 ACS patients with in-hospital bleeding. Among 4,679
      GUSTO mild/moderate bleeding events, only surgical and systemic bleeds were
      associated with an increased risk of 6-month death or myocardial infarction
      (adjusted hazard ratio [HR]: 2.52 [95% confidence interval (CI): 2.16 to 2.94,
      and 1.40 [95% CI: 1.16 to 1.69], respectively). Mild/moderate superficial and
      access-site bleeds were not associated with downstream risk (adjusted HR: 1.17
      [95% CI: 0.97 to 1.40], and 0.96 [95% CI: 0.82 to 1.12], respectively). Among 221
      GUSTO severe bleeds, surgical bleeds were associated with the highest risk (HR:
      5.27 [95% CI: 3.80 to 7.29]), followed by systemic (HR: 4.48 [95% CI: 2.98 to
      6.72]), and finally access-site bleeds (HR: 3.57 [95% CI: 2.35 to 5.40]).
      CONCLUSIONS: Among ACS patients who develop in-hospital bleeding, systemic and
      surgical bleeding are associated with the highest risks of adverse outcomes
      regardless of bleeding severity. Although the most frequent among bleeds, GUSTO
      mild/moderate access-site bleeding is not associated with increased risk. These
      data underscore the importance of strategies to minimize overall bleeding risk
      beyond vascular access site management.

PMID- 23866184
TI  - Relationship between myocardial reperfusion, infarct size, and mortality: the
      INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With
      Large Anterior Myocardial Infarction) trial.
AB  - OBJECTIVES: This study sought to compare infarct size (IS) measured by magnetic
      resonance imaging in patients with successful (myocardial blush grade [MBG] 2/3)
      versus unsuccessful (MBG 0/1) microcirculatory reperfusion in the INFUSE-AMI
      (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large
      Anterior Myocardial Infarction) trial. BACKGROUND: Successful microcirculatory
      reperfusion, defined angiographically by MBG 2 or 3, is associated with improved
      outcomes in patients with ST-segment elevation myocardial infarction. The precise
      mechanism underlying this association is not well defined. METHODS: The INFUSE
      AMI trial randomized 452 patients with anterior ST-segment elevation myocardial
      infarction to intracoronary bolus abciximab delivered locally at the infarct
      lesion versus no abciximab, and to manual thrombus aspiration versus no
      aspiration. The primary endpoint was IS (percentage of left ventricular mass) at
      30 days. RESULTS: MBG 2/3 was achieved in 367 patients (81.4%). IS was
      significantly lower in patients with MBG 2/3 than in those with MBG 0/1 (median:
      16.7% [interquartile range (IQR): 7.0 to 22.7] vs. 19.5% [IQR: 11.1 to 29.2]; p =
      0.002). Intracoronary abciximab further reduced IS in patients with MBG 2/3
      (median: 14.4% [IQR: 5.4 to 20.9] vs. 17.4% [IQR: 10.5 to 23.8]; p = 0.01). MBG
      2/3 was associated with ~30% reduction in infarct mass (p = 0.002) and ~90%
      reduction in microvascular obstruction on day 5. Ejection fraction was higher
      with MBG 2/3 at 30 days: median: 50.3% (IQR: 43.8 to 57.8) versus 46.9% (IQR:
      37.5 to 54.0); p = 0.004. At 30 days, the rate of death was significantly lower
      (1.7% vs. 8.3%; p = 0.0008) in the MBG 2/3 group. CONCLUSIONS: MBG 2/3 occurs in
      80% of ST-segment elevation myocardial infarction patients treated with primary
      percutaneous coronary intervention and is associated with smaller infarct size,
      less microvascular obstruction, improved ejection fraction, and significantly
      lower 30-day mortality. (Intracoronary Abciximab and Aspiration Thrombectomy in
      Patients With Large Anterior Myocardial Infarction [INFUSE-AMI]; NCT00976521).

PMID- 23866185
TI  - Prediction of 1-year mortality in patients with acute coronary syndromes
      undergoing percutaneous coronary intervention: validation of the logistic
      clinical SYNTAX (Synergy Between Percutaneous Coronary Interventions With Taxus
      and Cardiac Surgery) score.
AB  - OBJECTIVES: This study sought to validate the Logistic Clinical SYNTAX (Synergy
      Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score
      in patients with non-ST-segment elevation acute coronary syndromes (ACS), in
      order to further legitimize its clinical application. BACKGROUND: The Logistic
      Clinical SYNTAX score allows for an individualized prediction of 1-year mortality
      in patients undergoing contemporary percutaneous coronary intervention. It is
      composed of a "Core" Model (anatomical SYNTAX score, age, creatinine clearance,
      and left ventricular ejection fraction), and "Extended" Model (composed of an
      additional 6 clinical variables), and has previously been cross validated in 7
      contemporary stent trials (>6,000 patients). METHODS: One-year all-cause death
      was analyzed in 2,627 patients undergoing percutaneous coronary intervention from
      the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial.
      Mortality predictions from the Core and Extended Models were studied with respect
      to discrimination, that is, separation of those with and without 1-year all-cause
      death (assessed by the concordance [C] statistic), and calibration, that is,
      agreement between observed and predicted outcomes (assessed with validation
      plots). Decision curve analyses, which weight the harms (false positives) against
      benefits (true positives) of using a risk score to make mortality predictions,
      were undertaken to assess clinical usefulness. RESULTS: In the ACUITY trial, the
      median SYNTAX score was 9.0 (interquartile range 5.0 to 16.0); approximately 40%
      of patients had 3-vessel disease, 29% diabetes, and 85% underwent drug-eluting
      stent implantation. Validation plots confirmed agreement between observed and
      predicted mortality. The Core and Extended Models demonstrated substantial
      improvements in the discriminative ability for 1-year all-cause death compared
      with the anatomical SYNTAX score in isolation (C-statistics: SYNTAX score: 0.64,
      95% confidence interval [CI]: 0.56 to 0.71; Core Model: 0.74, 95% CI: 0.66 to
      0.79; Extended Model: 0.77, 95% CI: 0.70 to 0.83). Decision curve analyses
      confirmed the increasing ability to correctly identify patients who would die at
      1 year with the Extended Model versus the Core Model versus the anatomical SYNTAX
      score, over a wide range of thresholds for mortality risk predictions.
      CONCLUSIONS: Compared to the anatomical SYNTAX score alone, the Core and Extended
      Models of the Logistic Clinical SYNTAX score more accurately predicted individual
      1-year mortality in patients presenting with non-ST-segment elevation acute
      coronary syndromes undergoing percutaneous coronary intervention. These findings
      support the clinical application of the Logistic Clinical SYNTAX score.

PMID- 23866186
TI  - Asymptomatic giant coronary artery aneurysms: images from coronary angiography,
      IVUS, and echocardiography.

PMID- 23866187
TI  - Multimodality imaging of an anomalous connection of the right coronary artery
      with aortic intramural course.

PMID- 23866188
TI  - Biomechanical assessment of fully bioresorbable devices.

PMID- 23866189
TI  - Reply: To PMID 23428020.

PMID- 23866190
TI  - Closure of incompletely surgically-ligated left atrial appendage in reducing
      stroke risk.

PMID- 23866192
TI  - Optimization of Tryton dedicated coronary bifurcation system with coregistration
      of optical coherence tomography and fractional flow reserve.

PMID- 23866193
TI  - Coregistered intravascular ultrasound and optical coherence tomography imaging
      during implantation of a bioresorbable vascular scaffold.

PMID- 23866194
TI  - Left main coronary artery occlusion due to thrombus embolization from a
      prosthetic mitral valve.

PMID- 23866195
TI  - White-light photoluminescence and photoactivation in cadmium sulfide embedded in
      mesoporous silicon dioxide templates studied by confocal laser scanning
      microscopy.
AB  - SBA-15 and SBA-16 silica templates have been infiltrated with CdS by means of
      nanocasting using a hybrid precursor. The morphology and structure of both the
      SiO2@CdS nanocomposites and the silica-free CdS replicas have been characterized.
      The three-dimensional nanocrystalline CdS networks embedded in SBA-15 and SBA-16
      silica templates exhibit broad photoluminescence (PL) spectra over the entire
      visible range, together with enhanced PL intensity compared to silica-free CdS
      replicas. These effects result from the role silica plays in passivating the
      surface of the CdS mesostructures. Furthermore, photoactivation is eventually
      observed during continuous illumination because of both structural and chemical
      surface modifications. Owing to this combination of properties, these materials
      could be appealing for solid-state lighting, where ultra-bright near-white PL
      emission is indispensable. 

PMID- 23866196
TI  - Sulfonated macro-RAFT agents for the surfactant-free synthesis of cerium oxide
      based hybrid latexes.
AB  - Three types of amphiphatic macro-RAFT agents were employed as compatibilizers to
      promote the polymerization reaction at the surface of nanoceria for the synthesis
      of CeO2-based hybrid latexes. Macro-RAFT copolymers and terpolymers were first
      synthesized employing various combinations of butyl acrylate as a hydrophobic
      monomer and acrylic acid (AA) and/or 2-acrylamido-2-methylpropane sulfonic acid
      (AMPS) as hydrophilic monomers. After characterizing the adsorption of these
      macro-RAFT agents at the cerium oxide surface by UV-visible spectrometry,
      emulsion copolymerization reactions of styrene and methyl acrylate were then
      carried out in the presence of the surface-modified nanoceria. Dynamic Light
      Scattering and cryo-Transmission Electron Microscopy were employed to confirm the
      hybrid structure of the final CeO2/polymer latexes, and proved that the presence
      of acrylic acid units in amphiphatic macro-RAFT agents enabled an efficient
      formation of hybrid structures, while the presence of AMPS units, when combined
      with AA units, resulted in a better distribution of cerium oxide nanoclusters
      between latex particles. 

PMID- 23866197
TI  - Fabrication of monodisperse hollow silica spheres and effect on water vapor
      permeability of polyacrylate membrane.
AB  - Polystyrene/silica core-shell spheres were fabricated using polystyrene as
      templates by hydrolysis and condensation of tetraethyl orthosilicate through a
      sol-gel process, in which polystyrene was synthesized by emulsion polymerization.
      Then, hollow silica spheres were obtained after selective removal of the organic
      polystyrene core from the polystyrene/silica core-shell spheres by
      tetrahydrofuran etching. The effect of hollow silica spheres on water vapor
      permeability, mechanical property, and water uptake of polyacrylate membrane were
      investigated. The microstructure analysis shows that the mean size and wall
      thickness of hollow silica spheres are 170 nm and 20 nm, respectively. The silica
      shells consist of amorphous silica seed assembly with a broad size distribution,
      which roughen the surfaces of hollow silica spheres greatly. The specific surface
      area of hollow silica spheres is bigger than that of polystyrene/silica core
      shell spheres. Hollow silica spheres can significantly improve water vapor
      permeability of polyacrylate membrane, but lead to the reduction in mechanical
      property.

PMID- 23866198
TI  - Deformation and dewetting of thin liquid films induced by moving gas jets.
AB  - We study the deformation of thin liquid films subjected to impinging air-jets
      that are moving with respect to the substrate. The height profile and shape of
      the deformed liquid film is evaluated experimentally and numerically for
      different jet Reynolds numbers and translation speeds, for different liquids and
      substrate materials. Experiments and numerical results are in good agreement. On
      partially wetting substrates film rupture occurs. We imaged the appearance of dry
      spots and emergence of droplet patterns by high-speed, dual-wavelength
      interference microscopy. We systematically evaluated the resulting average
      droplet size and droplet density as a function of the experimental conditions. We
      show that within experimental accuracy the distribution of dry spots is dependent
      only on the residual film thickness and is not directly influenced by the shear
      stress and pressure gradients of the air-jet, nor by the speed of the substrate. 

PMID- 23866199
TI  - Interaction of Fe(III) and Al(III) during hydroxylation by forced hydrolysis: the
      nature of Al-Fe oxyhydroxy co-precipitates.
AB  - Al-Fe oxyhydroxy co-precipitates were synthesised by forced hydrolysis of
      Fe(NO3)3.9H2O and Al(NO3)3.9H2O solutions. Solids containing 0, 1, 10, 25, 50,
      75, 90 mol% Al were characterised for composition, texture, mineral structure and
      local atomic environment. Cation substitution in the hydrous oxides was not
      observed. The solids consisted of hydrous ferric oxide (HFO) nuclei surrounded by
      Al-hydroxide. Below 50 mol% Al, unit particle size, high specific surface area
      and microporosity of HFO were preserved. Al-K-edge XANES showed ordered
      arrangements of Al-octahedra suggesting that some Al bound specifically to HFO
      surface sites. Above 50 mol%, Al precipitated in multiple layers around the
      nuclei and also as individual entities. The HFO nuclei exhibited the general
      characteristics of a 2-line ferrihydrite. However, as Al increased, the structure
      was slightly modified. While the symmetry of the FeO6 octahedra improved, the
      number of Fe-Fe linkages decreased, suggesting less polymerisation. An
      organisation of the Fe-octahedra, faintly resembling akaganeite, was expressed in
      Raman spectra. These changes in HFO structure were attributed to hindrance in the
      progressive olation/oxolation of the primary Fe-hydroxypolymers, caused by Al
      bound to the surface of nuclei. The presence of nitrate is suspected to have
      favoured the structural changes.

PMID- 23866200
TI  - Functionalization of magnetic nanocrystals by oligo (ethylene oxide) chains
      carrying diazonium and iniferter end groups.
AB  - The water stability of iron oxide nanoparticles (NPs) is a major issue for
      biomedical and biological applications. This paper presents a versatile approach
      for preparing water-soluble iron oxide nanoparticles coated by bifunctional
      oligo(ethylene oxide) (OEO) chains, carrying on the one side a diazonium end
      group for covalent grafting at the NP surface and on the other side an iniferter
      group (diethyl dithiocarbamate) for initiating the growing of poly(methacrylic
      acid). The nanoparticles were synthesized by coprecipitation in basic media and
      functionalized in situ by adding the diazonium salt directly in the synthesis
      medium. Oligo(ethylene oxide) with various chain lengths (from one to three
      monomer units) was grafted at the NP surface using this approach. The length of
      the OEO spacer between the NP surface and the iniferter end group was found to be
      a critical parameter for controlling the colloidal stability of the hybrid NPs.
      The polymerization time was also shown to strongly influence their colloidal
      stability, emphasizing the interest to control the interfacial properties of the
      hybrids for obtaining stable dispersions in water. 

PMID- 23866201
TI  - Sub-150 nm mesoporous silica nanoparticles with tunable pore sizes and well
      ordered mesostructure for protein encapsulation.
AB  - Despite their great potentials as biomacromolecues delivery vehicles, there are
      few, if any, reports on mesoporous silica nanoparticles (MSNs) simultaneously
      integrated with the merits of large pore size, small particle diameters and well
      ordered mesostructure. Here, we designed a facile strategy for the synthesis of
      monodispersed MSNs using cationic surfactants (CSs) as templating agents, neutral
      amine of N,N-dimethylhexadecylamine (DMHA) as a pore size mediator and tri-block
      copolymer of F127 (EO106PO70EO106) as a particle growth inhibitor/dispersant. The
      obtained colloidal nanoparticles exhibited a highly ordered mesostructure and
      tunable pore diameter up to 4.6 nm (BJH) and monodispersed particle sizes less
      than 150 nm. A model protein of cytochrome c (CytC) was exemplified to be
      accommodated in the resultant MSNs and its loading amount was correlated with
      their pore size. The efficient cancer cellular uptake of the large-pore MSNs
      prefigured their potentials as intracellular delivery vehicles for membrane
      impermeable proteins.

PMID- 23866202
TI  - Surviving childhood cancer: relationship between exercise and coping on quality
      of life.
AB  - This research assesses Health-Related Quality of Life (HRQoL) in a Spanish sample
      of adolescent cancer survivors, and analyzes the relationship between HRQoL,
      coping styles and physical exercise. Forty-two survivors (12-19 years), who were
      >= 1 year of remission, completed standardized measures of HRQoL (CHIP-AE),
      coping strategies (ACS) and physical exercise (AECEF). Mean scores in all HRQoL
      domains were within normative values. Multiple regression analysis revealed that
      physical exercise and productive coping were related to higher HRQoL, whereas non
      productive coping was related to lower HRQoL. This sample of survivors reported
      good levels of HRQoL, which are mediated by coping styles and physical exercise. 

PMID- 23866203
TI  - Factor structure and reliability of the depression, anxiety and stress scales in
      a large Portuguese community sample.
AB  - The purpose of the present study was to assess the factor structure and
      reliability of the Depression, Anxiety and Stress Scales (DASS-21) in a large
      Portuguese community sample. Participants were 1020 adults (585 women and 435
      men), with a mean age of 36.74 (SD = 11.90) years. All scales revealed good
      reliability, with Cronbach's alpha values between .80 (anxiety) and .84
      (depression). The internal consistency of the total score was .92. Confirmatory
      factor analysis revealed that the best-fitting model (*CFI = .940, *RMSEA = .038)
      consisted of a latent component of general psychological distress (or negative
      affectivity) plus orthogonal depression, anxiety and stress factors. The
      Portuguese version of the DASS-21 showed good psychometric properties (factorial
      validity and reliability) and thus can be used as a reliable and valid instrument
      for measuring depression, anxiety and stress symptoms. 

PMID- 23866204
TI  - Contextual variables associated with psychosocial adjustment of adolescents.
AB  - This study investigated associations of contextual variables of risk (stressful
      events and exposure to community violence), variables of protection (family
      environment, connectivity to the school and community perceptions) and
      demographic variables (gender and age) with indicators of psychosocial adjustment
      (self-esteem, involvement in illegal activities and alcohol use in past month)
      among adolescents. The participants were 685 students (61.5% girls) aged between
      12 and 18 years (M = 15.10, SD = 1.52) of public schools in southern Brazil. They
      answered a questionnaire with 77 questions and an inventory for assessment of
      family relationships. Logistic regression analyses indicated that the negative
      perception of family environment, poor connectivity to the school and exposure to
      community violence were associated with low self-esteem. Involvement in illegal
      activities was associated with low connectivity to school, stressful events,
      exposure to community violence and male sex. Finally, alcohol use/month was
      associated with negative perception of the community, community violence,
      stressful events, and particularly at the ages of 15-16 years. 

PMID- 23866205
TI  - Pre-service science teachers' teaching self-efficacy in relation to personality
      traits and academic self-regulation.
AB  - The aim of this study is to examine the relationship among pre-service science
      teachers' personality traits, academic self-regulation and teaching self-efficacy
      by proposing and testing a conceptual model. For the specified purpose, 1794 pre
      service science teachers participated in the study. The Teachers' Sense of
      Efficacy Scale, the NEO Five-Factor Inventory, and the Motivated Strategies for
      Learning Questionnaire were administered to assess pre-service science teachers'
      teaching self-efficacy, personality, and academic self-regulation respectively.
      Results showed that agreeableness, neuroticism, performance approach goals, and
      use of metacognitive strategies are positively linked to different dimensions of
      teaching self-efficacy, namely self-efficacy for student engagement,
      instructional strategies, and classroom management. In general, while
      agreeableness and neuroticism were found to be positively associated with
      different facets of self-regulation and teaching self-efficacy, openness was
      found to be negatively linked to these adaptive outcomes. 

PMID- 23866206
TI  - Psychoticism and disruptive behavior can be also good predictors of school
      achievement.
AB  - The relations of Gf (Standard Progressive Matrices Raven), Gc (verbal scale of
      Wechsler Intelligence Scale for Children-Third Version), personality dimensions
      (Eysenck Personality Questionnaire-Junior Version), and disruptive behavior (TDAH
      scale) with school achievement (measured by TDE test and PISA test) were
      investigated. Two samples of students (total N = 534) representing a broad range
      of socioeconomic status (SES) participated in this study. Path models were
      conducted. The results demonstrated that (1) in both samples no sex differences
      related to school achievement were found; (2) in the first sample, after
      controlling for age and SES differences, Gf and psychoticism predicted (.38 and 
      .13, respectively) school achievement (measured by TDE test); (3) in the second
      sample, after controlling for SES differences to which additional measures were
      administered, Gf and Gc positively predicted (.22 and .40, respectively) school
      achievement (measured by PISA test). In addition, psychoticism and disruptive
      behavior also predicted school performance (-.14 and -.28, respectively). Some
      theoretical and practical implications are discussed. 

PMID- 23866207
TI  - Working memory as separable subsystems: a study with Portuguese primary school
      children.
AB  - Although much research has been done to study the working memory structure in
      children in their first school years, the relation of cognitive constructs
      involved in this process remains uncertain. In particular, it is unclear whether
      working memory is a domain general construct that coordinates separate codes of
      verbal and visuospatial storage or whether it is a domain-specific construct with
      distinct resources of verbal and visuospatial information. This paper
      investigates the structure of working memory, by using the Working Memory Test
      Battery for Children (WMTB-C) and by doing confirmatory factor analyses (CFAs) on
      a sample of Portuguese children (n = 103) between 8 and 9 years of age. The
      results of the confirmatory factor analyses that provide the best fit of the data
      correspond to the model that includes Central Executive and Visuospatial
      Sketchpad in the same factor, co-varying with a Phonological Loop factor.
      Moreover, the traditional working memory tripartite structure--based on the
      Baddeley and Hitch Model--revealed good fit to the data.

PMID- 23866208
TI  - Spanish adaptation of the structural empowerment scale.
AB  - The present study's objective is to create a Spanish adaptation of the Conditions
      of Work Effectiveness Questionnaire II (CWEQ-II) by Laschinger, Finegan, Shamian,
      and Wilk (2004) in order to measure structural empowerment in an organizational
      context. To do so, this study was conducted in two distinct phases. In the first,
      a group of experts carried out a back-translation of the questionnaire and in the
      second phase, we analyzed the questionnaire's internal structure (through
      exploratory and confirmatory factor analysis) and external validity. The
      resulting Spanish version of the questionnaire (CWEQ-S) demonstrated/exhibited
      good factor structure and good psychometric properties as far as reliability and
      validity are concerned. 

PMID- 23866209
TI  - Quality of life in disability: validation of Schalock's multi-dimensional model
      in the Portuguese context.
AB  - This paper aims to evaluate the validation of Schalock's quality of life multi
      dimensional model (1996) in the Portuguese context. We also analyze the quality
      of life of disabled people by adding a political dimension (adapted from the
      Minorities' Rights Support Scale by Nata & Menezes, 2007) to this construct and
      seeking to understand the impact of discrimination. The sample is composed of 217
      participants, most of whom have a physical disability, aged 16 to 81. Validation
      procedures of the Quality of Life Questionnaire (Schalock & Keith, 1993) and
      descriptive statistics and correlation analysis were conducted. Confirmatory
      Factor Analysis revealed good local and global fit indices, and the internal
      consistency of the scales was satisfactory. An adapted version of the instrument
      composed of five scales-satisfaction, competence, empowerment, equality of rights
      and positive discrimination-is proposed. The results reveal the importance of
      rights and empowerment for the quality of life of disabled people and indicate a
      strong critical consciousness concerning the experience of discrimination in
      different contexts. Taken together, the findings indicate the strong need for
      social and political changes in this domain. 

PMID- 23866210
TI  - Body image and subjective well-being in Portuguese adolescents.
AB  - The study examines the impact of body image in adolescents' well-being. Well
      being was assessed with the scale Kidscreen10, with the Cantril ladder for
      satisfaction with life and with an ad hoc happiness scale. The study presents
      data on adolescent health from the Health Behavior in School-aged Children
      (HBSC)/World Health Organization study in Portugal (2006), with a sample of 4,877
      adolescents, average age of 14 years old and gender distribution at 49,6% males.
      Portuguese adolescents showed differences between gender and age group regarding
      their body image-related satisfaction/dissatisfaction and self-perceived body
      image, being that both components have a direct impact on the levels of well
      being. The male gender has better results in the perception of body image and,
      consequently, well-being. The largest inter-gender differences for well-being is
      at 15 years of age. The main predictors of well-being are the look and body
      satisfaction/dissatisfaction, with greater importance on the affective component.
      This research highlights the importance of body image for adolescents' well
      being, as well as to prepare educational strategies adapted to adolescents' age
      and gender, by helping them to develop skills concerning self-knowledge and
      caring for their look. 

PMID- 23866211
TI  - Temperament and behavior problems in toddlers born preterm and very low birth
      weight.
AB  - The purpose of the present study was to examine the temperament and behavior
      problems of 32 toddlers born preterm and very low birth weight and 25 toddlers
      born full-term without medical problems. Mothers completed the Early Childhood
      Behavior Questionnaire and the Child Behavior Checklist-1.5-5 for assessing
      toddler's temperament and behavior problems, respectively. The results showed
      that, regarding temperament, toddlers born preterm exhibited higher scores on the
      temperament dimensions Motor Activation, Perceptual Sensitivity, and High
      Intensity Pleasure, and lower scores on the temperament dimension Cuddliness than
      toddlers born full-term. In regard to behavior problems, toddlers born preterm
      showed higher attention problems scores than the comparison group. These findings
      indicated that children born preterm presented developmental vulnerabilities in
      temperament dimensions related to behavior problems at toddlerhood. Early
      intervention programs for preventing psychological problems in at-risk children,
      especially those born preterm, could focus on children's temperament
      dispositions. 

PMID- 23866212
TI  - Measuring subjective resilience despite adversity due to family, peers and
      teachers.
AB  - The objective of this study is to develop and validate a scale of subjective
      resilience for students 12-17 years old. Items covered adverse situations due to
      parents', peers' and teachers' actions. The validation process included the
      analysis on the generalizability of the factor structure and of relationships of
      resilience scores with different kinds of protective and vulnerability factors 
      goal orientations and learning-oriented classroom motivational climate (CMC)-. A
      total of 471 students answered four questionnaires. Confirmatory factor analyses,
      reliability analysis and correlation and regression analyses were carried out.
      Results showed: (a) that factor structure was well defined; (b) that resilience
      scale had good reliability; (c) that scores correlated as expected with
      protective-vulnerability factors such as goal orientations and CMC defined by
      teachers' teaching-patterns, and (d) that students' attribution of perceived
      change in resilience to teachers' work depended on the degree in which CMC was
      learning oriented. Theoretical and practical implications are discussed. 

PMID- 23866213
TI  - Pathological gamblers and a non-psychiatric control group taking gender
      differences into account.
AB  - The current study aimed to identify personality traits, emotional states and
      adjustment variables in a sample of pathological gamblers as compared to a non
      gambling control group taking gender differences into account. The sample for
      this study consisted of 206 subjects (103 pathological gamblers and 103 non
      psychiatric subjects from the general population matched for age and gender).
      Pathological gamblers had a lower educational level and a family history of
      alcohol abuse higher than non-gamblers. In turn, female gamblers were affected by
      unemployment and a lower socioeconomic status more often than female non
      gamblers. Pathological gamblers were more anxious and impulsive and suffered from
      a poorer self-esteem than non-gamblers. Likewise, pathological gamblers had a
      greater history of other Axis I psychiatric disorders and were more often
      affected by anxiety and depression symptoms and showed a more problematic
      adjustment to everyday life than non-gamblers. Alcohol abuse was not higher in
      pathological gamblers than in non-gamblers, but, when gender was taken into
      account, male gamblers were more affected by alcohol abuse than male non
      gamblers. Importantly 68.6% of female gamblers versus 9.8% of control group women
      reported being victims of intimate partner violence. These findings can be used
      to specifically inform prevention and intervention efforts. 

PMID- 23866214
TI  - Psychometric properties of a test for ADHD based on binocular rivalry.
AB  - The psychometric properties of a Binocular Rivalry (BR)-based test on a group of
      159 participants (57 with attention deficit hyperactivity disorder, ADHD) aged
      between 6 and 15 years are presented. Two factors, which explained 56.82% of the
      variance, were obtained by exploratory factor analysis: (a) Alternations and
      Duration of exclusive dominances, and (b) Decision time. Reliability was
      excellent (Cronbach's alpha = .834 and .884). The ADHD group showed fewer
      alternations and longer duration of dominances and decision time than the control
      group. Correlations between measures of BR, IQ, working memory, and processing
      speed of the WISC-IV, and ADHD symptoms, assessed by parents and teachers, ranged
      between low and medium. 

PMID- 23866215
TI  - Bullying in Spanish secondary schools: gender-based differences.
AB  - The aim of this study was to determine the prevalence of bullying in its various
      forms from the perspective of all of the individuals involved (victims, bullies,
      and witnesses) and to explore its distribution as a function of gender. The study
      had a correlational design and used a representative sample of 1500 Spanish
      students attending compulsory secondary education in the academic year 2007-2008.
      It applied an instrument measuring different types of bullying, taken from the
      studies conducted by Diaz-Aguado, Martinez, and Martin (2004) and the Defensor
      del Pueblo (Spanish Ombudsman's Office)-UNICEF (2007). The findings reveal that
      all the types of bullying considered take place at school and that there is an
      inverse relationship between the severity and the prevalence of bullying
      behaviors, with verbal abuse proving to be the most common type of abusive
      behavior. Boys are involved in all kinds of bullying incidents as bullies
      significantly more often than girls are, except in cases involving 'talking about
      someone behind their back'; in these situations, girls are involved significantly
      more often as bullies than boys are. As for victimization, boys are victims of
      direct physical abuse significantly more often than girls are, while girls are
      more often the subject of malicious gossip. 

PMID- 23866216
TI  - An analysis of the relationship between victimization and violent behavior at
      school.
AB  - Previous studies have identified two subgroups of school violence victims:
      submissive and aggressive. Submissive victims are characterized by their
      withdrawal in violent situations, while aggressive victims combine hostile
      behavior with victimization. This study focuses on the second subgroup and aims
      to analyze possible factors influencing the transition from passive victimization
      to involvement in aggressive behaviors within the school context. To test these
      relationships, 1319 adolescents between 12 and 16 years of age were recruited
      from seven secondary schools in various Spanish provinces. Structural equation
      modeling techniques were used to analyze the data. Results supported Emler's
      theory, which posits that the victim's helplessness in situations of
      intimidation, along with disappointment resulting from a lack of expected
      protection from adult authority figures, may result in adolescents searching and
      developing an antisocial and non-conformist reputation that helps them defend
      themselves against future attacks. Practical implications of these results are
      further discussed. 

PMID- 23866217
TI  - Workplace attachment and meaning of work in a French secondary school.
AB  - This research aims to gain a better understanding of the attachment of teachers
      to their workplace by identifying the areas to which they become attached and
      which give meaning to their work. Based on the belief that place attachment is an
      affective bond between a person and his or her environment (Bonnes & Secchiaroli,
      1995), its aim is to identify the attachment of secondary school teachers to
      their workplace, which is viewed as a whole but also as a combination of specific
      places, and to show that the places that predict overall workplace attachment are
      also those that give meaning to work. A Workplace Attachment Scale was completed
      by 158 teachers in a secondary school in the Paris region (France). This
      questionnaire contained items evaluating attachment to each specific place of
      work and others adapted from the meaning-of-work scale evaluating the meaning
      given to each of these places. The results show that all the teachers were more
      closely attached to places that provide opportunities for informal communication
      than to those directly related to teaching. The main workplace attachment
      predictors also concern places constituting the essence of the profession and/or
      places where teachers can manage their organizational stress. 

PMID- 23866218
TI  - Learning of facial responses to faces associated with positive or negative
      emotional expressions.
AB  - The possibility that facial expressions of emotion change the affective valence
      of faces through associative learning was explored using facial electromyography
      (EMG). In Experiment 1, EMG activity was registered while the participants (N =
      57) viewed sequences of neutral faces (Stimulus 1 or S1) changing to either a
      happy or an angry expression (Stimulus 2 or S2). As a consequence of learning,
      participants who showed patterning of facial responses in the presence of angry
      and happy faces, that is, higher Corrugator Supercilii (CS) activity in the
      presence of angry faces and higher Zygomaticus Major (ZM) activity in the
      presence of happy faces, showed also a similar pattern when viewing the
      corresponding S1 faces. Explicit evaluations made by an independent sample of
      participants (Experiment 2) showed that evaluation of S1 faces was changed
      according to the emotional expression with which they had been associated. These
      results are consistent with an interpretation of rapid facial reactions to faces
      as affective responses that reflect the valence of the stimulus and that are
      sensitive to learned changes in the affective meaning of faces. 

PMID- 23866219
TI  - Psychometric properties of the screen for child anxiety related emotional
      disorders for socially anxious and healthy Spanish adolescents.
AB  - Socially anxious and healthy Spanish adolescents were studied in order to test
      the psychometric properties of the Screen for Child Anxiety Related Emotional
      Disorders (SCARED). Confirmatory factor analyses were employed to test
      measurement invariance between these two populations, Cronbach's alphas were
      calculated to determine the reliabilities of the scales, and partial eta-square
      tests calculated the effect size of the differences between socially anxious and
      healthy adolescents and between the adolescent boys and girls. The psychometric
      properties of the SCARED were good, as demonstrated by having acceptable
      reliabilities (ranging from .75 - .41) and a moderate multivariate effect size
      (eta(p)(2) = .08) between the adolescent boys and girls. Most importantly, it was
      demonstrated that the SCARED could differentiate between socially anxious and
      healthy Spanish adolescents as demonstrated by measurement invariance (chi(2) =
      254.27, df = 1343, GFI = .884, AGFI = .872, RMR = .031) and the large effect size
      (eta(p)(2) = .22) between the samples.

PMID- 23866220
TI  - Self-generated explanations on the question demands are not always helpful.
AB  - This study had two main purposes. First, to measure high-school students' task
      model representation under the instruction to self-explain questions; second, to
      test the effects of self-generated explanations on task-demands understanding and
      performance on questions. We designed a simple experimental situation where high
      school students were asked to read two texts and answer questions. Only in half
      of the questions students were required to self-explain with their own words what
      the question was asking them for before answering. Contrary to our expectations,
      self-explaining the questions did not significantly affect skilled comprehenders,
      whereas it hindered performance in less-skilled comprehenders. Moreover, it
      inhibited their active engagement in search for textual units of information.
      Less-skilled comprehenders' explanation protocols included inaccuracies, with
      consequences on the search process and success in the task. The relationship
      among quality of task model, search for information and success is discussed in
      light of the TRACE model (Rouet, 2006). 

PMID- 23866221
TI  - Spanish version of the new ecological paradigm scale for children.
AB  - The New Ecological Paradigm (NEP) scale has been extensively used to measure
      adults' environmental attitudes. However, it has only recently been adapted for
      use with children. This paper presents a Spanish version of the NEP Scale for
      Children, examines children's ecological beliefs according to socio-demographic
      variables as well as the relationship between children's ecological beliefs and
      pro-environmental behavior. Exploratory factor analysis was conducted, followed
      by confirmatory factor analysis. In addition, the instrument's internal
      consistency was studied and links between environmental attitudes, age, and
      ecological behavior in children were examined through correlation analyses. The
      results show that children's ecological worldviews can be described by a
      dimension called "overall ecocentrism". Analysis of variance demonstrated that
      children from rural areas exhibit a more ecocentric worldview than those from
      urban areas. The results also denote gender differences. 

PMID- 23866222
TI  - Measurement invariance study of the training satisfaction questionnaire (TSQ).
AB  - This article presents an empirical measurement invariance study in the
      substantive area of satisfaction evaluation in training programs. Specifically,
      it (I) provides an empirical solution to the lack of explicit measurement models
      of satisfaction scales, offering a way of analyzing and operationalizing the
      substantive theoretical dimensions; (II) outlines and discusses the analytical
      consequences of considering the effects of categorizing supposedly continuous
      variables, which are not usually taken into account; (III) presents empirical
      results from a measurement invariance study based on 5,272 participants'
      responses to a training satisfaction questionnaire in three different
      organizations and in two different training methods, taking into account the
      factor structure of the measured construct and the ordinal nature of the recorded
      data; and (IV) describes the substantive implications in the area of training
      satisfaction evaluation, such as the usefulness of the training satisfaction
      questionnaire to measure satisfaction in different organizations and different
      training methods. It also discusses further research based on these findings. 

PMID- 23866223
TI  - Teacher psychological needs, locus of control and engagement.
AB  - This study examines the relationships among psychological needs, locus of control
      and engagement in a sample of 282 Spanish secondary school teachers. Nine teacher
      needs were identified based on the study of Bess (1977) and on the Self
      Determination Theory (Deci & Ryan, 1985, 2000, 2002). Self-report questionnaires
      were used to measure the construct selected for this study and their
      interrelationships were examined by conducting hierarchical regression analyses.
      An analysis of teacher responses using hierarchical regression reveals that
      psychological needs have significant positive effects on the three engagement
      dimensions (vigor, dedication and absorption). Furthermore, the results show the
      moderator role played by locus of control in the relationship between teacher
      psychological needs and the so-called core of engagement (vigor and dedication).
      Finally, practical implications are discussed. 

PMID- 23866224
TI  - Cardiovascular response to psychosocial repeated stress in caregivers of
      offspring with schizophrenia.
AB  - Taking care of offspring suffering a long-term illness such as schizophrenia is
      one of the more stressful life experiences. Care conditions may act as a
      protective factor in the health of the caregiver. The present study assesses
      heart rate (HR), blood pressure (BP), and mood responses to psychosocial stress
      in 16 mothers receiving specialised support for the care of their offspring
      (CARE+) and in 11 mothers caring for their offspring without support (CARE-). The
      CARE- group take care of less functional and more symptomatic offspring; and
      display higher basal, but lower HR, responses after stress than the CARE+ group.
      No significant group effects were found for BP. For mood states, there were
      significant decreases in the anger subscale in the CARE- group that were not
      found in the CARE+ group. HR was related to active and passive coping styles,
      trait anxiety, and years spent providing care. In the total sample, other
      significant relationships between cardiovascular responses and life events and
      personality traits have been found. In sum, the data suggests that specialised
      support for patients may modulate cardiovascular responses to repeated stress in
      caregivers. 

PMID- 23866225
TI  - HIV- and AIDS-related stigma: psychosocial aspects in a representative Spanish
      sample.
AB  - This study evaluates the prevalence of HIV stigma in Spain and analyzes some
      variables that may affect its existence. In 2008, we conducted a computer
      assisted telephone survey of 1607 people, representative of the Spanish
      population. Two-wave random stratified sampling was performed, first selecting
      the home and then the person, depending on the rates of age and sex. About 50% of
      the population feels discomfort about potential contact with people with HIV and
      tries to avoid it and 20% advocate discriminatory policies involving physical or
      social segregation of people with HIV. The belief that HIV is easily transmitted
      through social contact (15%) and blaming people with HIV for their disease
      (19.3%) are associated with stigmatization. Degree of proximity to people with
      HIV, political ideology, educational level, and age are also associated with the
      degree of stigmatization. According to these results, we suggest that, in order
      to reduce stigma, we need to modify the erroneous beliefs about the transmission
      pathways, decrease attributions of blame to people with HIV, and increase contact
      with them. These interventions should particularly target older people, people
      with a low educational level, and people with a more conservative political
      ideology. 

PMID- 23866226
TI  - A psychology of liberation for Central America: the unfinished work of Ignacio
      Martin-Baro (1942-1989).
AB  - On November 16, 1989 the world was shocked by the news of the assassination of
      six Jesuits at the campus of the Universidad Centro Americana Jose Simeon Canas
      (UCA) in San Salvador, El Salvador. Among those murdered by government soldiers
      was Ignacio Martin-Baro, a PhD in social psychology from the University of
      Chicago who at that time was the Vice-Rector for Academic Affairs and Vice
      President of the Interamerican Society of Psychology (SIP). Drawing on Martin
      Baro's published writings and non-published academic papers and correspondence,
      this article traces the evolution of the Spanish-born Jesuit who became a leading
      authority among Latin American social psychologists. In particular, it analyzes
      his project of becoming a clinical psychologist under the influence of
      psychoanalysis, his critical social psychology aimed to "de-ideologize" the
      oppressed social classes of El Salvador, and his ultimate project of a psychology
      of liberation for Latin America. Martin-Baro's work came to a tragic end just
      when it began to bear fruit, but it stands as a testimony to a lifetime committed
      to the human values of democracy, social justice and service to society's poorest
      and most neglected. 

PMID- 23866227
TI  - Prespeech vocalizations and the emergence of speech: a study of 1005 Spanish
      children.
AB  - This study investigates 12 prespeech vocal behaviors which are taken to reflect
      children's phonological, communicative and early symbolic development. It
      explores their development (onset, duration and extinction) and their relation to
      early lexical development. A structured parental questionnaire on prespeech
      vocalizations was developed, validated and used for the evaluation of 1005
      Spanish children's early vocal development (8-30 months). In parallel, the same
      children's productive vocabulary was assessed using the vocabulary section of the
      European-Spanish MacArthur-Bates Communicative Development Inventories. Results
      highlight a global inverted U-shaped developmental pattern which emerges from the
      asynchronous development of the vocal behaviors examined, relating both their
      emergence and extinction to advances in linguistic development. Moreover, the
      protracted coexistence of prespeech vocalizations with early speech and their
      significant correlations with vocabulary size reveal a gradual transition into
      language. Overall results reinforce and extend previous findings on the
      development of prespeech vocalizations and establish their relevance as early
      indexes of linguistic development. Finally, positive evidence on the use of an
      assisted parental report method for reliably evaluating these developments is
      provided. Results are discussed within theoretical frameworks that conceive
      language as the emergent product of complex developmental processes.

PMID- 23866228
TI  - Black and white or shades of grey? Comparing social representations centrality
      models.
AB  - The present study, aligned with the structural approach on social representations
      (SR), aimed at comparing dichotomous (central vs. peripheral) and continuous
      models of structural status of SR elements. The sample was formed by 114
      undergraduate students who completed context independence tasks and resistance to
      change evaluations related to 30 elements from 3 SR objects. Non-nested
      regression models having resistance to change as the criterion variable and
      dichotomous and continuous operationalizations of symbolic value as predictors
      were compared. Statistical results complemented by follow-up t-tests challenge
      the dichotomous model and support a continuous quadratic one. The curve is
      interpreted as being related to different evaluations when elements are
      attributed to a majority or a minority and point out to the need to employ within
      subjects designs in future research assessing more properties with composite
      measures. 

PMID- 23866229
TI  - Temperament and behavioral problems of preschool children with headache--a
      controlled study.
AB  - The purpose of this study was to compare differences in temperament and emotional
      and behavioral problems in a community sample of young children who experience
      headaches to those without such complaints. The whole sample was comprised 75 non
      referred, preschool-aged children (3-5 years old), including 22 with headache
      complaints and 53 without headaches (control group). The children's headache
      symptoms were assessed with a questionnaire that was given to the mothers.
      Rothbart's Children's Behavior Questionnaire was used to assess temperament, and
      the Child Behavior Checklist 1 1/2-5 was used to assess emotional and behavioral
      problems. Compared with the control group, children with headache complaints
      showed more discomfort, which is the amount of negative affect induced by the
      sensory qualities of stimulation, including intensity, rate, or complexity of
      light, movement, sound, texture, or a combination of these modes of stimuli.
      These children also had higher scores for externalizing and internalizing
      emotional and behavioral problems compared to children without headaches. These
      findings show that the preschool-aged children with headaches presented more
      emotional and behavioral problems than the control group. 

PMID- 23866230
TI  - Professional training in the workplace: the role of achievement motivation and
      locus of control.
AB  - The core objective of the present work is to explore the reasons why workers from
      different employment sectors join training courses to improve their job. To this
      end we assessed achievement motivation, locus of control and professional
      qualifications according to the participants' employment sector. The final sample
      consisted of 1460 active Spanish workers from four different employment sectors:
      services, catering, metal construction, and others. Of the sample, 40.1% were
      male and 59.9% female, with a mean age of 33.3 years (SD = 9.7). The results show
      that the new scale developed to assess achievement motivation, locus of control
      and workers' qualifications presents adequate psychometric characteristics.
      Statistically significant differences were found in relation to employment
      sector. The areas studied showed satisfactory levels of workers' effort and
      achievement motivation to perform their jobs, though their attitudes toward the
      training courses as a basis for improving their employability are varied. Workers
      in the catering sector had higher levels of external attribution and the lowest
      interest in training. Those in the service sector had higher levels of
      achievement motivation and effort at work. Future research should develop a joint
      program covering the public and private sectors for the modification of these
      beliefs, attitudes and attributions. 

PMID- 23866231
TI  - Social intelligence as a predictor of loneliness in the workplace.
AB  - The aim of this research is to examine the relationship between social
      intelligence and loneliness of academics in the workplace. This study involves
      326 (149 female/177 male) academics employed in various universities in Turkey
      and North Cyprus. The age average of participants is 39.09 years. In this study,
      the Loneliness at Work Scale (LAWS) and Tromso Social Intelligence Scale (TSIS)
      have been utilized. The data were analyzed using multiple regression and Pearson
      product-moment correlation coefficient analysis techniques. The findings showed
      that social information processing, social skills, and social awareness, which
      are the sub-dimensions of social intelligence, positively explained 26% of social
      deprivation. Social skills and social awareness positively explained 13% of
      social companionship. The findings also showed that the social information
      processing sub-dimension did not meaningfully explain social companionship. 

PMID- 23866232
TI  - Aggressive behavior in children: the role of temperament and family
      socialization.
AB  - This study's objective is to analyze temperament and parenting variables as they
      relate to proactive and reactive aggression in children. To be specific, profiles
      based on these variables were analyzed in children with high levels of proactive
      versus reactive aggression. The sample was made up of two groups: 482 children
      (52.3% boys) between 1 and 3 years-old, and 422 children (42.42% boys) 3 to 6
      years-old. Statistical analyses of the two age groups included: Pearson's
      correlations to explore the relationships among variables, Cluster Analysis to
      create groups with different levels of aggression, and finally discriminant
      analysis to determine which variables discriminate between groups. The results
      show that high levels of frustration/negative affect in the 1-3 year-old group
      and low effortful control in children 3 to 6 years old are the most relevant
      variables in differentiating between aggressive and non-aggressive subjects.
      Nevertheless, differential profiles of subjects with high levels of proactive
      versus reactive aggression were not observed. The implications of these different
      types of aggression in terms of development and prevention are discussed.

PMID- 23866233
TI  - Retiring from elite sports in Greece and Spain.
AB  - The main objective of the present study was to compare the athletic retirement of
      elite Greek and Spanish athletes in terms of (a) pre-conditions of retirement,
      (b) transitional period, and (c) consequences of the transition. For this
      purpose, elite athletes from Greece (n = 76) and Spain (n = 57) described in
      retrospect their experience leaving competitive sports through the Retirement
      from Sports Survey (Alfermann, Stambulova, & Zemaityte, 2004). Separate one-way
      ANOVAs and chi-square tests revealed differences and similarities between the
      transitional processes of athletes from the two countries. More similarities than
      differences were detected in the retirement of Greek and Spanish athletes. Based
      on these commonalities, we proposed a Southern European perspective on the topic.
      According to the present results the main characteristics of this pattern could
      be the lack of retirement planning, high athletic identity after the sports
      career, and predominance of relocation in the sports world after retirement. 

PMID- 23866234
TI  - Parental stress and children adjustment in kinship foster families.
AB  - This work focuses on a multidimensional exploration of the stress experienced by
      kinship foster carers. This study is the first one conducted on Spanish sample,
      with 116 kinship foster families and foster children, between the ages of 4 and
      11 years. In general, data indicate that the carer's parental stress scores are
      within the normative range. The existing heterogeneity among these families is
      also reported, highlighting a carers group with high stress levels. Parental
      stress correlated with children variables (initial adversity index, adaptation,
      evolution and behavioral adjustment); caregiver and family variables (main
      carer's health, no correlation was found with social support network or with
      economic needs) and child-carer relationship variables (acceptance-rejection,
      relationship with the main caregiver and with other family members). Finally, the
      predictive model performed shows that the more behavioral and emotional problems
      foster children exhibit, the more stress the carers experience. This is also true
      the worse the relationships with other relatives are and the poorer the health of
      the main carer is. 

PMID- 23866235
TI  - Relationship between stress symptoms and drug use among secondary students.
AB  - The aim of this study was to evaluate the relationship between drug use and four
      kinds of stress symptoms in 954 Brazilian students from the 6th to the 11th
      grades, in 4 public and 5 private schools in the city of Sao Paulo. Based on
      their answers to the Drug Use Screening Inventory (DUSI-R) and to the Stress
      Scale for Adolescents (SSA), we compared regular drug users with non/occasional
      drug users regarding the frequency of four kinds of stress symptoms
      (psychological, cognitive, physiological, interpersonal), and the period in which
      it happened. When compared to non/occasional drug users, regular drug users
      presented higher levels of psychological, cognitive and physiological symptoms of
      stress and these symptoms were in the most severe spectrum of severity (near to
      exhaustion and exhaustion). The association between drug use and stress was even
      stronger in the youngest age group (11 to 13 years old). Most of the regular drug
      users were 16 years old and over, from upper-middle class families, had poor
      family relationships and more academic problems. These results confirm the
      association between drug use and stress in adolescents and highlight the need for
      early screening and intervention in both drug use and stressful situations.

PMID- 23866236
TI  - Context of treatment and therapeutic alliance: critical factors in court-mandated
      batterer intervention programs.
AB  - This paper deals with the influence of the therapeutic context in batterer
      intervention programs. We conducted 2 complementary studies: a descriptive
      analysis (Study 1) and a qualitative study (Study 2) analyzing the aspects that
      may help to improve the operation and effectiveness of treatment in a group of
      men (N = 27) who participated in a program for convicted perpetrators of intimate
      partner violence. The results show a statistically significant relationship
      between the therapeutic alliance and the assessment of the usefulness of the
      program attended by offenders (r = .69, p < .01), and between the therapeutic
      alliance and the assessment of the usefulness of the program content (r = .43, p
      < .05). Furthermore, the results of the qualitative analysis show that aspects of
      the therapeutic context may play an important role for the adhesion of offenders
      to treatment, increasing their motivation and improving results. It is proposed
      that future research should provide more in-depth analysis of the elements
      related to the context of the intervention and therapists' skills as facilitators
      of change. 

PMID- 23866237
TI  - Development patterns of executive functions in children.
AB  - Executive Functions (EF) exercise control over an individual's conduct and
      thinking through a set of functionally independent processes, among which are
      cognitive flexibility (reactive and spontaneous), working memory and planning.
      The development patterns of these components appear to have stages of
      acceleration and deceleration during childhood. Studies analyzing their
      development in Spanish-speaking children were not found in our area. Therefore,
      this study will analyze the development patterns of the cited executive functions
      with the objective of establishing relationships and comparisons, and identifying
      the stages of acceleration and stagnation for each component. The study's sample
      consists of 274 schoolchildren between the ages of 6 and 8 (119 in first grade,
      61 in second grade and 94 in third grade). Participants were evaluated using the
      following instruments from the Neuropsychological Assessment of Children test
      battery (known by the acronym ENI in Spanish): Verbal Fluency (semantic and
      phonemic); Cognitive Flexibility; Mexican Pyramid; and Backward Digit Span. Three
      different development patterns were detected, as well as different interactions
      between the executive components. Additionally, three empirical types were
      established based on the patterns and relationships between components. 

PMID- 23866238
TI  - Construction and validation of the community and socio-political participation
      scale (SCAP).
AB  - This article describes the development and validation of a new instrument, the
      scale (SCAP) which measures community participation (CP) and socio-political
      participation (SPP). The sample consists of 756 participants in Malaga, residents
      whose average age is 38.78 years old (SD = 13.96) and of whom 58.5% are women.
      The results endorse the psychometric qualities of the instrument. We present
      descriptive analysis of the items, the dimensionality of the scale and its
      internal consistency. The external evidence of validity shows positive and
      statistically significant correlations with sense of community and empowerment,
      variables theoretically related to participation. A confirmatory factor analysis
      confirms the two-dimensional structure (CP and SPP). Further analysis show a
      higher CP in women. This instrument extends the quantitative research on citizen
      participation. 

PMID- 23866239
TI  - Interaction with the game and motivation among players of massively multiplayer
      online role-playing games.
AB  - Knowledge about users interacting with Massively Multiplayer Online Role-Playing
      Games (MMORPG) is fundamental in order to prevent their potential negative
      effects on behavior. For this reason, the present study analyzed the relationship
      between styles of play and motivations. An online questionnaire asking for socio
      demographic details, playing style, characteristics of the game played and
      motivations for playing, was answered by 430 Spanish-speaking MMORPG players
      (45.1% males). The identified profile for players, far away from the stereotype
      of an adolescent, consisted in a person who mainly plays on PvP (Player versus
      Player) servers, choosing the type of game according to his experience. Regarding
      motivations, they were interested in relating with other players through the game
      (Socialization), in discovering the game's possibilities and development of its
      adventures (Exploration), to a lesser extent in leadership and prestige
      (Achievement) and, lastly, identification with an avatar and escape from reality
      (Dissociation). Although part of the reason for playing was escapism and/or
      stress relief, the main motivation had a social nature. We conclude that MMORPG
      offer an attractive environment for a broad spectrum of people, and we have not
      been able to confirm the stereotype of a loner avoiding reality, taking refuge in
      games. 

PMID- 23866240
TI  - Dimensions of familial allocentrism in Brazilian mothers from state capitals and
      small cities.
AB  - This study focuses on 606 Brazilian women's cultural models regarding their
      relation with their family, as evaluated by the Family Allocentrism Idiocentrism
      Scale (FAS). The scale was translated into Portuguese, submitted to back
      translation and adapted. Analyses of the scale's structure indicated that the
      best fit model involves two independent factors. Univariate GLM (General Linear
      Model) analyses showed that the place where mothers were raised presented a
      significant effect on their scores on factor 1 (normative familial allocentrism).
      Mothers raised on rural areas have higher scores on this factor, than the ones
      raised on urban areas. The opposite occurred with factor 2 (relational familial
      allocentrism). The set of evidences indicate that the FAS may be a bi-dimensional
      measure. One dimension would be part of a more stable and basic model of relation
      to family, constructed during development. The second dimension would be related
      to more recent experiences and would be more readily affected by socio-cultural
      context changes, including in acculturation processes. 

PMID- 23866241
TI  - Expressed and perceived criticism, family warmth, and symptoms in schizophrenia.
AB  - Criticism directed by caregivers towards a family member with schizophrenia, both
      from the perspective of the patient and of the caregiver, predicts relapse,
      although both perspectives differ. This study aims to verify if the same applies
      to a Mediterranean sample, where criticism is not the main attitude of high
      expressed emotion families. The Camberwell Family Interview was applied to assess
      the family's perspective, and the Perceived Criticism and the Family Emotional
      Involvement and Criticism Scales were used to assess the patients' perspective,
      in 21 dyads. The association between both perspectives and psychotic symptoms was
      also examined. Results replicated those of previous studies in other countries,
      revealing that the perspectives on Criticism of patients and families do not
      match. The fact that family members also presented positive attitudes towards the
      patient did not cushion the patient's perceived criticism. Thus, it seems that
      families considered to be critical may not be perceived as such by the patients.
      Furthermore, only the warmth from the family's perspective correlated with the
      symptoms: positive affect proved to be more relevant than negative affect.
      Therefore, the patients' subjective assessments and family warmth should be
      included in clinical and research proposals. 

PMID- 23866242
TI  - Unpredictability and context conditioning: does the nature of the US matter?
AB  - Using a conditioned suppression task, we examined the minimal conditions to
      establish context conditioning as induced by unpredictability of an unconditioned
      stimulus (US). We investigated whether a biologically significant US is necessary
      to produce such context conditioning effects. In this between-subjects
      experiment, we manipulated the nature of the US and US-unpredictability. In the
      Paired condition, the conditioned stimulus (CS) was always followed by the US,
      whereas in the Unpaired condition, the CS and the US were presented explicitly
      unpaired, that is, the CS was never followed by the US. Half of the participants
      received an aversive, biologically significant human scream, and the other half
      received a more neutral, biologically non-significant sound as US. Results show
      more contextual suppression in the Unpaired condition than in the Paired
      condition. We conclude that in an expectancy-based conditioning task, US
      unpredictability, but not a biologically potent US, is crucial to establish
      context conditioning. 

PMID- 23866243
TI  - The perceived stress scale (PSS): normative data and factor structure for a large
      scale sample in Mexico.
AB  - One of the most widely used scales for the evaluation of stress is the Perceived
      Stress Scale (PSS), and it has been adapted into different languages. However,
      few studies have presented normative data from large samples, and there do not
      appear to be any studies of the PSS that provide normative data based on large
      samples for Mexico. Thus, the goal of this study was to provide normative data
      regarding gender and different age groups for a sample of 1990 Mexican subjects
      to validate the factor structure of the construct for this sample. The analysis
      of the 10- and 14-item versions of the PSS revealed that the scale had adequate
      reliability and that the factor structure was consistent with previous studies.
      With respect to the normative data, the means of the different groups ranged from
      20.93 to 25.63 for the PSS14 and from 14.52 to 17.73 for the PSS10. We propose
      that scores within one standard deviation of these means be used as reference
      values for each group. 

PMID- 23866244
TI  - Disability profile/clinician-rated: validity for Brazilian university students
      with social anxiety disorder.
AB  - Functional impairment scales are important to assess Social Anxiety Disorder
      (SAD) patients. The present study aims to evaluate the reliability, internal
      consistency, validity and factorial structure of the Disability Profile/Clinician
      Rate (DP) scale, as well as to present an interview-guide to support its
      application by clinicians. University students (n = 173) of both genders
      participated in the study (SAD = 84 and Non-SAD = 89), with ages ranging between
      17 and 35 years, systematically diagnosed. The SAD group presented more
      difficulties when compared to the Non-SAD group. The DP presented, for the SAD
      group, internal consistency of 0.68 (lifetime) and 0.67 (last two weeks). Inter
      rater reliability varied from 0.75 to 0.93. Two factors were extracted and the
      correlation among such factors and the Social Phobia Inventory subscales
      presented association between fear and avoidance symptoms and the functional
      impairments. The scale presents good psychometric properties and can contribute
      to the assessment of functional impairments. 

PMID- 23866245
TI  - Differences in psychosocial risk variables for HIV as a function of sexual
      experience.
AB  - The aim of this study was to analyze the differences in psychosocial risk
      variables for HIV as a function of sexual experience in an adolescent population.
      The study sample consisted of 846 adolescents of both sexes aged between 14 and
      19 years. Participants responded to several questionnaires that assessed four
      psychosocial variables related to risk sexual behavior for HIV infection: 1)
      perception of peer group norms, 2) condom use self-efficacy, 3) attitudes towards
      condom use and 4) parental communication about sexuality, STIs, HIV and
      pregnancy. Participants in both groups with sexual experience (with and without
      penetration) reported better communication with their mothers on sexuality and
      scored higher in positive attitudes towards condom use than those in the group
      without sexual experience. The sexual experience with penetration group perceived
      more negative peer group norms related to safe sexual behavior than the group
      without sexual experience; the group without sexual experience had a higher
      perception of condom use self-efficacy than the sexual experience with
      penetration group. 

PMID- 23866246
TI  - Associative relationships in human predictive learning.
AB  - Two experiments were conducted to explore the associations involved in human
      predictive learning. Experiment 1 found that post-training devaluation of one of
      the outcomes by instructing participants that one of the attackers was
      indestructible, led to a significant decrease in participants' predictive
      responses to the cue that was initially followed by the devalued outcome,
      suggesting that cue-outcome associations play a major role in human simple
      predictive learning. In Experiment 2, immediately after receiving cue-outcome
      predictive judgment training, participants were instructed to destroy the
      attackers by using the same responses previously used to give predictive
      judgments, but they were not informed as to which response should be used on each
      attacker. During a test in which both attackers were present at the same time,
      when the cue was present, participants preferentially chose the instrumental
      response alternative that was previously used as a predictive judgment about the
      relationship between the present cue and its outcome. In the absence of cues,
      participants equally chose either response alternative. This transfer of control
      shows that participants also establish judgment-outcome associations during
      predictive training. 

PMID- 23866247
TI  - Emotional intelligence and self-efficacy: effects on psychological well-being in
      college students.
AB  - The present paper examined the role of perceived emotional intelligence-EI-
      (measured by adaptations of the Trait Meta-Mood Scale - TMMS, Salovey, Mayer,
      Goldman, Turvey, & Palfai, 1995) as a predictor of life satisfaction and mental
      health. We explored the unique contribution of EI dimensions (Attention, Clarity
      and Repair) on individuals' psychological well-being, after controlling for the
      influence of general self-efficacy and socio-demographic variables (age, gender
      and culture). Data was collected from a sample of 1078 Spanish, Mexican,
      Portuguese and Brazilian undergraduate students (M(age) = 22.98; SD = 6.73) and
      analyzed using hierarchical multiple regressions. Results indicated that overall
      EI dimensions (especially Clarity and Repair) accounted for unique variance on
      psychological well-being above and beyond general self-efficacy and socio
      demographic characteristics. These findings provide additional support for the
      validity of perceived EI, and suggests that EI components contribute to important
      well-being criteria independently from well-known constructs such as self
      efficacy.

PMID- 23866248
TI  - The role of morphology in reading in Spanish-speaking children with dyslexia.
AB  - Morphemes facilitate visual word recognition, leading to greater accuracy and
      fluency in reading morphologically complex words. In children with dyslexia, the
      morphological structure might be useful to reduce difficulties caused by
      phonological deficits. The aim of this study was to determine whether Spanish
      speaking children with dyslexia benefit from morphemes when reading. A group of
      children with dyslexia of different ages (7 to 10 years) and a group of children
      without reading disabilities, matched on chronological age and gender,
      participated in a task of reading isolated words and pseudowords in which
      morphological complexity was manipulated. Half of the stimuli were
      morphologically simple and half morphologically complex. Children with dyslexia
      benefit from morphology since they have better performance with the
      morphologically complex stimuli. These results indicate that they are able to
      develop representations of units larger than the grapheme, what suggests that
      Spanish-speaking children with dyslexia use the morphological structure to
      overcome their difficulties in phonological recoding. These results have
      important implications for the rehabilitation of children with dyslexia. 

PMID- 23866249
TI  - Facial affect recognition in myasthenia gravis.
AB  - The assessment of facial expression is an important aspect of a clinical
      neurological examination, both as an indicator of a mood disorder and as a sign
      of neurological damage. To date, although studies have been conducted on certain
      psychosocial aspects of myasthenia, such as quality of life and anxiety, and on
      neuropsychological aspects such as memory, no studies have directly assessed
      facial emotion recognition accuracy. The aim of this study was to assess the
      facial emotion recognition accuracy (fear, surprise, sadness, happiness, anger,
      and disgust), empathy, and reaction time of patients with myasthenia. Thirty-five
      patients with myasthenia and 36 healthy controls were tested for their ability to
      differentiate emotional facial expressions. Participants were matched with
      respect to age, gender, and education level. Their ability to differentiate
      emotional facial expressions was evaluated using the computer-based program Feel
      Test. The data showed that myasthenic patients scored significantly lower (p <
      0.05) than healthy controls in the total Feel score, fear, surprise, and higher
      reaction time. The findings suggest that the ability to recognize facial affect
      may be reduced in individuals with myasthenia. 

PMID- 23866250
TI  - A smile radiates outwards and biases the eye expression.
AB  - This study investigated how extrafoveally seen smiles influence the viewers'
      perception of non-happy eyes in a face. A smiling mouth appeared in composite
      faces with incongruent (angry, fearful, neutral, etc.) eyes, thus producing
      blended expressions, or they appeared in intact faces with genuine expressions.
      Overt attention to the eye region was spatially cued, foveal vision of the mouth
      was blocked by gaze-contingent masking, and the distance between the eyes and the
      mouth was varied. Participants evaluated whether the eyes were happy or not.
      Results indicated that the same non-happy eyes were more likely to be judged as
      happy, and more slowly to be judged as not happy, in presence more than in
      absence of a smile. As (a) the smiling mouth was highly salient regardless of
      type of eyes, (b) the influence on the eyes increased gradually as a function of
      eye-mouth proximity, and (c) the effect occurred in the absence of fixations on
      the mouth, we conclude that a salient smile radiates outwards to other face
      regions through a projection mechanism, thus making the eye expression look
      happy. 

PMID- 23866251
TI  - Multilevel models in the explanation of the relationship between safety climate
      and safe behavior.
AB  - This study examines the relationships between components of organizational safety
      climate, including employee attitudes to organizational safety issues;
      perceptions of the physical working environment, and evaluations of worker
      engagement with safety issues; and relates these to self-reported levels of
      safety behavior. It attempts to explore the relationships between these variables
      in 1189 workers across 78 work groups in a large transportation organization.
      Evaluations of safety climate, the working environment and worker engagement, as
      well as safe behaviors, were collected using a self report questionnaire. The
      multilevel analysis showed that both levels of evaluation (the work group and the
      individual), and some cross-level interactions, were significant in explaining
      safe behaviors. Analyses revealed that a number of variables, at both levels,
      were associated with worker engagement and safe behaviors. The results suggest
      that, while individual evaluations of safety issues are important, there is also
      a role for the fostering of collective safety climates in encouraging safe
      behaviors and therefore reducing accidents. 

PMID- 23866252
TI  - Dimensionality of the inventory of parent and peer attachment: evaluation with
      the Spanish version.
AB  - Three studies aimed at developing the Spanish version of the Inventory of Parent
      and Peer Attachment (IPPA; Armsden & Greenberg, 1987) and at analyzing its factor
      structure are reported. In Study 1, the Spanish translation of items and their
      content analysis was carried out via cognitive interviews. In Study 2, the three
      factor structure proposed by authors was tested in a sample of 417 adolescents
      (270 girls and 147 boys) using confirmatory analysis, and indexes showed a
      suboptimal fit. A principal component analysis yielded one-dimensional structures
      in father, mother and peer versions, explaining 54.3%, 50.8%, and 50.8% of the
      variance respectively. On the basis of the factor loadings and of the item-total
      correlations, a shortened version of the inventory was created. Convergent
      validity was tested with measures of family climate, parenting socialization and
      self-esteem. In Study 3, the one-dimension structure was confirmed in a new
      sample of 604 adolescents (335 girls and 269 boys). Based on all factor analyses
      and convergent validity indices obtained, we conclude that the Spanish IPPA
      questionnaire reliably and validly assesses adolescent attachment using only a
      dimension of attachment security. 

PMID- 23866253
TI  - Labelling improves false belief understanding. A training study.
AB  - A total of 104 children aged between 41 and 47 months were selected to study the
      relationship between language and false belief understanding. Participants were
      assigned to four different training conditions: discourse, labelling, control
      (all with deceptive objects), and sentential complements (involving non-deceptive
      objects). Post-test results showed an improvement in children's false belief
      understanding in the discourse and the labelling conditions, but not in the
      sentential complements with non-deceptive objects or the control group.
      Furthermore, the most remarkable improvement in false belief understanding
      occurred in the labelling group. These results suggest that some types of
      linguistic experience promote the development of false belief understanding,
      provided that differing perspectives are confronted. 

PMID- 23866254
TI  - Prototypicality and intensity of emotional faces using an anchor-point method.
AB  - Emotional faces are commonly used as stimuli in a wide number of research fields.
      The present study provides values of 198 pictures from one of the amplest
      available face databases, the Karolinska Directed Emotional Faces (KDEF). We used
      a new validation strategy that consisted of presenting pairs of faces which
      included an emotional face (i.e., angry, happy, sad) and its corresponding
      neutral face from the same model. This design allowed participants to keep a
      comparison face (i.e., neutral) as a constant anchor point to evaluate parameters
      on each emotional expression presented. Raters were asked to judge both the
      prototypicality of the emotional expressions (i.e., the degree to which they
      represent their corresponding emotional prototypes) as well as their emotional
      intensity. We finally discuss the potential advantages of this anchor-point
      method as a system to elicit judgments on facial emotional expressions. 

PMID- 23866255
TI  - Discriminant profile of young adulthood driving behavior among Brazilian drivers.
AB  - The aim of this article was to describe the driving behavior profile of drivers
      aged 18 to 25 years old. Four hundred young adults were interviewed, 320 (80%) of
      them male and 80 (20%) female. Cluster analysis identified a group characterized
      by sensation-seeking behavior (Cluster 1), a group that did not show any risky
      driving behavior (Cluster 2), and a group engaged in transgressive behavior and
      driving under the influence of alcohol and/or drugs (Cluster 3). Discriminant
      analysis classified successfully and correctly 81.3% of the young adults into
      their original profiles. Function 1 distinguished cluster 1 from clusters 2 and
      3, on the basis of the following factors: higher frequency of alcohol
      consumption, intrusive behavior, and motorcycle riding, as well as younger age,
      more aggressive behavior, and lower education level. Function 2 distinguished
      cluster 3 from cluster 1 and 2, especially as to higher amounts of alcohol
      consumption, higher frequency of marijuana use and delinquent behavior, larger
      number of traffic tickets and motor vehicle accidents, higher paternal education
      level, which were the variables with discriminant values above .20.
      Characteristics of vulnerability were identified, especially those related to
      alcohol consumption, drug use, and externalizing issues. 

PMID- 23866256
TI  - Age differences in executive functions within a sample of Brazilian children and
      adolescents.
AB  - Executive abilities have been suggested to show differential age-related changes.
      This study aimed to extend this evidence to a Brazilian sample, which was
      composed of 572 children and adolescents aged 6 to 14 years, assessed in tests of
      visual and auditory working memory, selective attention, inhibitory control,
      cognitive flexibility, attentional abilities, verbal fluency and planning. ANOVAs
      revealed significant age effect on performance in all tests, with a trend toward
      better performance with the progression of age, even in differential ways.
      Overall, the performance on simpler tests, such as the basic attention, increased
      with age progression until around 11 or 12 years, when performance becomes more
      stable. However, in more complex tasks, including working memory tasks, the
      performance showed a more continuous improvement. There was gender effect in two
      measures: visual working memory, in which boys outperformed girls, and verbal
      fluency, in which the girls outperformed boys. In general, the results of this
      Brazilian sample were similar to those reported by studies conducted in other
      countries, what suggests that Brazilian socio-cultural specificities, at least of
      the participants of this sample, were not sufficient to reveal a distinct pattern
      of progression. 

PMID- 23866257
TI  - Late developing mammary tumors and hyperplasia induced by a low-oncogenic variant
      of mouse mammary tumor virus (MMTV) express genes identical to those induced by
      canonical MMTV.
AB  - BACKGROUND: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of
      C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months
      of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the
      overexpression of common core insertion site (CIS) genes, including Wnt1/10b,
      Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in
      C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces
      premalignant mammary lesions and tumors with reduced incidence and longer latency
      than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core
      CIS genes. FINDINGS: We confirmed the presence of active virus in Mtv-1/NIV
      infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found
      that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the
      core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3. CONCLUSIONS: These results underscore
      the importance of core CIS gene expression in the early events leading to MMTV
      induced mammary tumor initiation regardless of the viral variant.

PMID- 23866258
TI  - Clinical relevance of different biomarkers in imported plasmodium falciparum
      malaria in adults: a case control study.
AB  - BACKGROUND: For rapid initiation of anti-malarial treatment and prevention of
      complications, early diagnosis and risk stratification is important in patients
      with Plasmodium falciparum malaria. Routine laboratory values do not correlate
      well with disease severity. The aim of this study was to determine the diagnostic
      and prognostic value of several biomarkers related to inflammation; endothelial
      and cardiac dysfunction; coagulation, and haemolysis in imported P. falciparum
      malaria. METHODS: In a prospective case-control study, 79 adult travellers with
      both uncomplicated and complicated P. falciparum malaria were included between
      2007 and 2011. Forty-one healthy subjects were included as controls. Blood
      samples were obtained within 24 hours after first consultation to assess routine
      laboratory values as well as markers related to inflammation (PAPP-A, copeptin,
      CRP), endothelial activation (MPO, elastase-2, endothelin-1, sICAM-1, sVCAM-1),
      cardiac function (NT-proBNP, MR-proANP), coagulation (fibrinogen, D-dimers,
      platelet count), and haemolysis (LDH). Prognostic performance was assessed using
      the receiver operating characteristic curve (area under the curve = AUROC).
      RESULTS: Twelve (15.2%) patients had severe P. falciparum malaria. In the patient
      group, significant thrombocytopaenia was found, all other markers but PAPP-A were
      significantly elevated. Diagnostic performance was best for CRP with an AUROC of
      1.00, followed by MPO (0.99), D-dimers (0.98), elastase-2 (0.98), and sICAM-1
      (0.98). Biomarker levels did not correlate well with disease severity.
      CONCLUSION: The combination of travel history, fever prior to blood sampling, and
      CRP serum levels above or below 10.8 mg/l upon hospital admission, best
      discriminated between malaria patients and control persons. None of the
      biomarkers studied predicted the presence or the development of malaria
      complications, neither at the time of admission, nor during hospitalization.

PMID- 23866259
TI  - Testing the association between social capital and health over time: a family
      based design.
AB  - BACKGROUND: The past decade has seen a vast increase in empirical research
      investigating associations between social capital and health outcomes. Literature
      reviews reveal 'generalized trust' and 'social participation' to be the most
      robust of the commonly used social capital proxies, both showing positive
      association with health outcomes. However, this association could be confounded
      by unmeasured factors, such as the shared environment. Currently, there is a
      distinct lack of social capital research that takes into account such residual
      confounding. METHODS: Using data from the United Kingdom's British Household
      Panel Survey (BHPS) (waves thirteen to eighteen, N = 6982), this longitudinal,
      multilevel study investigates the validity of the association between trust,
      social participation and self-rated health using a family-based design. As the
      BHPS samples on entire households, we employed 'mean' and 'difference from the
      mean' aggregate measures of social capital, the latter of which is considered a
      social capital measurement that is not biased by the shared environment of the
      household. We employed Generalized Estimating Equations for all analyses, our two
      level model controlling for correlation at the household level. RESULTS: Results
      show that after adjusting for the shared environment of the household over a six
      year period, the association between social participation and self-rated health
      was fully attenuated (OR = 0.97 (95% confidence interval 0.89-1.06)), while the
      association with trust remained significant (OR = 1.11 (1.02-1.20)). Other health
      determinants, such as being a smoker, having no formal qualifications and being
      unemployed maintain their associations with poor self-rated health. CONCLUSIONS:
      The association between social capital (specifically trust and social
      participation) and self-rated health appear to be confounded by shared
      environmental factors not previously considered by researchers. However, the
      association with trust remains, adding to existing empirical evidence that
      generalized trust may be an independent predictor of health.

PMID- 23866261
TI  - Examining inter-generational differentials in maternal health care service
      utilization: insights from the Indian Demographic and Health Survey.
AB  - This study examines the association between age cohort and utilization of
      maternal health care services in India, before and after adjusting for
      individual, household and contextual factors. Using data from the Demographic and
      Health Survey 2005-06, women were classified into three distinct age cohorts
      based on their age at childbirth: 15-24, 25-34 and 35-49 years. Binary logistic
      regression models were applied to assess the influence of women's age cohort on
      receiving full antenatal care (ANC) and skilled birth attendance (SBA). The
      analytical sample included the women who delivered their most recent birth at any
      time in the 5 years preceding the survey. Women belonging to the younger age
      cohort were found to be disadvantaged in receiving full ANC, whereas increasing
      age of women was negatively associated with receiving SBA. Low level of
      education, low mass media exposure, low autonomy, belonging to deprived social
      groups, poor economic status and residence in the central region were found to be
      major constraining factors in receiving full ANC and SBA for women in India. The
      findings support the need for 'age-sensitive' interventions that tailor
      programmes and incentives to women's health care needs through the reproductive
      life-stage. Urgent efforts are needed to ensure that women who are illiterate and
      those belonging to low autonomy and low socioeconomic groups receive the
      recommended maternal health care benefits.

PMID- 23866260
TI  - The effects of Gamijinhae-tang on elastase/lipopolysaccharide-induced lung
      inflammation in an animal model of acute lung injury.
AB  - BACKGROUND: Gamijinhae-tang (GJHT) has long been used in Korea to treat
      respiratory diseases. The therapeutic effect of GJHT is likely associated with
      its anti-inflammatory activity. However, the precise mechanisms underlying its
      effects are unknown. This study was conducted to evaluate the protective effects
      of GJHT in a porcine pancreatic elastase (PPE) and lipopolysaccharide(LPS)
      induced animal model of acute lung injury (ALI). METHODS: In this study, mice
      were intranasally exposed to PPE and LPS for 4 weeks to induce chronic
      obstructive pulmonary disease (COPD)-like lung inflammation. Two hours prior to
      PPE and LPS administration, the treatment group was administered GJHT extracts
      via an oral injection. The numbers of neutrophils, lymphocytes, macrophages and
      total cells in the bronchoalveolar lavage (BAL) fluid were counted, and pro
      inflammatory cytokines were also measured. For histologic analysis, hematoxylin
      and eosin (H&E) stains and periodic acid-Schiff (PAS) stains were evaluated.
      RESULTS: After inducing ALI by treating mice with PPE and LPS for 4 weeks, the
      numbers of neutrophils, lymphocytes and total cells were significantly lower in
      the GJHT group than in the ALI group. In addition, the IL-1beta and IL-6 levels
      were significantly decreased in the GJHT group. The histological results also
      demonstrated the attenuation effect of GJHT on PPE- and LPS-induced lung
      inflammation. CONCLUSIONS: The results of this study indicate that GJHT has
      significantly reduces PPE- and LPS-induced lung inflammation. The remarkable
      protective effects of GJHT suggest its therapeutic potential in COPD treatment.

PMID- 23866262
TI  - Exploring methods to prioritise concentration ratios when estimating weighted
      absorbed dose rates to terrestrial Reference Animals and Plants.
AB  - The ICRP and IAEA have recently reported Concentration Ratio values (CRwo-media-
      equilibrium radionuclide activity concentration in whole organism divided by that
      in media) for Reference Animals and Plants (RAPs) and a wide range of organism
      groups, respectively, based on a common online database. Given the large number
      of data gaps in both publications, there is a need to develop methods for
      identifying the relative importance of improving currently available CR(wo-media)
      values. A simple, transparent approach involving the derivation and comparison of
      predicted internal and external weighted absorbed dose rates for radionuclides
      considered by ICRP (2009) for terrestrial RAPs is presented. Using the approach
      of applying a reference value of CR(wo-soil) = 1 or using the maximum reported
      values where CR(wo-soil) >1, we provisionally identify terrestrial radionuclide
      RAP combinations which could be considered low priority, notably: Ca, Cr and Ni
      consistently; Mn for all RAPs except Deer and Pine Tree; and Tc for all RAPs but
      Wild Grass. Equally, we can systematically identify high priority elements and
      radioisotopes, which largely, but not exclusively, consist of alpha-emitters
      (especially isotopes of Ra and Th, but also consistently Am, Cf, Cm, Np, Pa, Po,
      Pu, U). The analysis highlights the importance of the radiation weighting factor
      default assumption of 10 for alpha-emitters in the ERICA Tool when comparing the
      magnitude of the internal dose and trying to identify high priority RAP-isotope
      combinations. If the unweighted Dose Conversion Coefficient (DCC) values are
      considered, those for alpha-emitters are often one order of magnitude higher than
      those due to some beta-gamma emitters for terrestrial RAPs, whereas with the
      radiation weighting factor applied they are two orders of magnitude higher.

PMID- 23866263
TI  - A comparison of dosimetric parameters between tomotherapy and three-dimensional
      conformal radiotherapy in rectal cancer.
AB  - PURPOSE: Tomotherapy for intensity-modulated radiation has been demonstrated to
      reduce unnecessary irradiations to adjacent organs at risk (OARs). The purpose of
      this study was to compare the dosimetric parameters between Tomotherapy and three
      dimensional conformal radiotherapy (3D-CRT) in rectal cancer patients. MATERIALS
      AND METHODS: We redesigned three-dimensional conformal plans for 20 rectal cancer
      patients who had received short-course preoperative radiotherapy with
      Tomotherapy. The target coverage for 3D-CRT and Tomotherapy was evaluated with
      the following including the mean dose, V(nGy), D(min), D(max), radiation
      conformality index (RCI), and radical dose homogeneity index (rDHI). RESULTS: The
      mean PTV dose for Tomotherapy is significantly higher than that observed for the
      3D-CRT (p = 0.043). However, there is no significant difference in the
      V(23.25Gy), V(26.25Gy), V(27.5Gy), and RCI values between Tomotherapy and 3D-CRT.
      However, the average rDHI (p < 0.001) value for Tomotherapy was significantly
      lower than that reported for the 3D-CRT. Tomotherapy significantly lowered the
      mean level of irradiation doses to the bladder, small bowel, and femur heads as
      compared to 3D-CRT. CONCLUSIONS: Tomotherapy could produce a favorable target
      coverage and significant dose reduction for the OARs at the expense of acceptable
      dose inhomogeneity of the PTV compared with 3D-CRT in rectal cancer patients.

PMID- 23866264
TI  - Serum ferritin contributes to racial or geographic disparities in metabolic
      syndrome in Taiwan.
AB  - OBJECTIVES: Asians and Pacific Islanders have higher circulating serum ferritin
      (SF) compared with Caucasians but the clinical significance of this is unclear.
      There is a higher prevalence of metabolic syndrome (MetS) in Taiwanese Indigenous
      than Han Chinese. Genetically, Indigenous are related to Austronesians and
      account for 2 % of Taiwan's population. We tested the hypothesis that
      accumulation of Fe in the body contributes to the ethnic/racial disparities in
      MetS in Taiwan. DESIGN: A population-based, cross-sectional study. SETTING:
      National Nutrition and Health Survey in Taiwan and Penghu Island. SUBJECTS: A
      total of 2638 healthy adults aged >=19 years. Three ethnic groups were included.
      RESULTS: Han Chinese and Indigenous people had comparable levels of SF.
      Austronesia origin was independently associated with MetS (OR = 2.61, 95 % CI
      2.02, 3.36). After multiple adjustments, the odds for MetS (OR = 2.49, 95 % CI
      1.15, 5.28) was significantly higher among Indigenous people in the highest SF
      tertile compared with those in the lowest tertile. Hakka and Penghu Islanders
      yielded the lowest risks (OR = 1.08, 95 % CI 0.44, 2.65 and OR = 1.21, 95 % CI
      0.52, 2.78, respectively). Indigenous people in the highest SF tertile had
      increased risk for abnormal levels of fasting glucose (OR = 2.34, 95 % CI 1.27,
      4.29), TAG (OR = 1.94, 95 % CI 1.11, 3.39) and HDL-cholesterol (OR = 2.10, 95 %
      CI 1.18, 3.73) than those in the lowest SF tertile. CONCLUSIONS: Our results
      raise the possibility that ethnic/racial differences in body Fe store
      susceptibility may contribute to racial and geographic disparities in MetS.

PMID- 23866265
TI  - Superovulation induces defective methylation in line-1 retrotransposon elements
      in blastocyst.
AB  - BACKGROUND: Series of epigenetic events happen during preimplantation
      development. Therefore assistant reproduction techniques (ART) have the potential
      to disrupt epigenetic regulation during embryo development. The purpose of this
      study was to investigate whether defects in methylation patterns in blastocyst
      due to superovulation originate from abnormal expression of Dnmts. METHODS: Low-
      (6 IU) and high- (10 IU) dosage of PMSG was used to stimulate the female mice.
      The metaphase II(MII) oocytes, zygotes and blastocyst stage embryos were
      collected. Global methylation and methylation at H3K9 in zygote, and methylation
      at repeated sequence Line 1 and IAP in blastocysts were assayed. In addition,
      expression of Dnmts was examined in oocytes and zygotes. RESULTS: Global DNA
      methylation and methylation at H3K9 in zygotes derived from females after low- or
      high-dosage hormone treatment were unaltered compared to that in controls.
      Moreover, DNA methylation at IAP in blastocysts was also unaffected, regardless
      of hormone dosage. In contrast, methylation at Line1 decreased when high-dose
      hormone was administered. Unexpectedly, expression of Dnmt3a, Dnmt3b, Dnmt3L as
      well as maintenance Dnmt1o in oocytes and zygotes was not disrupted. CONCLUSIONS:
      The results suggest that defects in embryonic methylation patterns do not
      originate from the disruption of Dnmt expression.

PMID- 23866267
TI  - Dietary predictors of childhood obesity in a representative sample of children in
      north east of Iran.
AB  - OBJECTIVE: The prevalence of obesity is increasing in Iranian youngsters. This
      study aimed to assess some dietary determinants of obesity in a representative
      sample of children in Neishabour, a city in northeastern, Iran. METHODS: This
      case-control study was conducted among 114 school students, aged 6-12 years, with
      a body mass index (BMI) >=95th (based on percentile of Iranian children) as the
      case group and 102 age- and gender-matched controls, who were selected from their
      non-obese classmates. Nutrient intake data were collected by trained
      nutritionists by using two 24-hour-dietary recalls through maternal interviews in
      the presence of their child. A food frequency questionnaire was used for
      detecting the snack consumption patterns. Statistical analysis was done using
      univariate and multivariate logistic regression (MLR) by SPSS version 16.
      RESULTS: In univariate logistic regression, total energy, protein, carbohydrate,
      fat (including saturated, mono- and poly-unsaturated fat), and dietary fiber were
      the positive predictors of obesity in studied children. The estimated crude ORs
      for frequency of corn-based extruded snacks, carbonated beverages, potato chips,
      fast foods, and chocolate consumption were statistically significant. After MLR
      analysis, the association of obesity remained significant with energy intake (OR
      = 2.489, 95%CI: 1.667-3.716), frequency of corn-based extruded snacks (OR =
      1.122, 95%CI: 1.007-1.250), and potato chips (OR = 1.143, 95%CI:1.024-1.276). The
      MLR analysis showed that dietary fiber (OR = 0.601, 95%CI: 0.368-0.983) and
      natural fruit juice intake (OR = 0.909, 95%CI: 0.835-0.988) were protective
      factors against obesity. CONCLUSIONS: The findings serve to confirm the role of
      an unhealthy diet, notably calorie-dense snacks, in childhood obesity. Healthy
      dietary habits, such as the consumption of high-fiber foods, should be encouraged
      among children.

PMID- 23866266
TI  - Down's syndrome, neuroinflammation, and Alzheimer neuropathogenesis.
AB  - Down syndrome (DS) is the result of triplication of chromosome 21 (trisomy 21)
      and is the prevailing cause of mental retardation. In addition to the mental
      deficiencies and physical anomalies noted at birth, triplication of chromosome 21
      gene products results in the neuropathological and cognitive changes of
      Alzheimer's disease (AD). Mapping of the gene that encodes the precursor protein
      (APP) of the beta-amyloid (Abeta) present in the Abeta plaques in both AD and DS
      to chromosome 21 was strong evidence that this chromosome 21 gene product was a
      principal neuropathogenic culprit in AD as well as DS. The discovery of
      neuroinflammatory changes, including dramatic proliferation of activated glia
      overexpressing a chromosome 2 gene product--the pluripotent immune cytokine
      interleukin-1 (IL-1)--and a chromosome 21 gene product--S100B--in the brains of
      fetuses, neonates, and children with DS opened the possibility that early events
      in Alzheimer pathogenesis were driven by cytokines. The specific chromosome 21
      gene products and the complexity of the mechanisms they engender that give rise
      to the neuroinflammatory responses noted in fetal development of the DS brain and
      their potential as accelerators of Alzheimer neuropathogenesis in DS are topics
      of this review, particularly as they relate to development and propagation of
      neuroinflammation, the consequences of which are recognized clinically and
      neuropathologically as Alzheimer's disease.

PMID- 23866268
TI  - [Expression of zinc finger protein X-linked in childhood B lineage acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: To study the expression of zinc finger protein X-linked (ZFX) in bone
      marrow mononuclear cells (BMMCs) of children with B lineage acute lymphoblastic
      leukemia (B-ALL) and its relationship with prognosis. METHODS: The expression of
      ZFX in human leukemia cell lines (REH, HL-60, NB(4) and K562) was measured by
      Western blot. ZFX gene was cloned by PCR from one patient and DNA sequencing
      technology was used to confirm it. Real-time PCR was used for detecting ZFX mRNA
      expression in the BMMCs of 82 children with newly-diagnosed B-ALL, 24 children
      with complete remission (CR) after induction therapy and 64 control children
      (fracture or congenital heart disease patients). According to the presence of
      bone marrow or central nervous system relapse during a follow-up of 3 years, the
      patients were identified as having a good or poor prognosis. Their ZFX mRNA
      levels in BMMCs at diagnosis were compared. RESULTS: ZFX protein was expressed in
      human leukemia cell lines REH, HL-60, NB(4) and K562. ZFX mRNA expression was
      significantly higher in the newly-diagnosed ALL group than in the control group
      (P < 0.01). ZFX mRNA expression in the ALL CR group was significantly reduced
      compared with the newly-diagnosed ALL group (P < 0.01). Children with a poor
      prognosis had significantly higher ZFX mRNA levels at diagnosis than those with a
      good prognosis (P < 0.05). CONCLUSIONS: ZFX is over-expressed in children with B
      ALL and its levels are higher in those with a poor prognosis than those with a
      good prognosis, which suggests that ZFX is important in the prognosis evaluation
      of B-ALL.

PMID- 23866269
TI  - [Clinical analysis of 28 cases of pediatric myelodysplastic syndrome].
AB  - OBJECTIVE: To explore the clinical features, diagnosis and treatment of pediatric
      myelodysplastic syndrome (MDS). METHODS: Twenty-eight children with MDS between
      January 2006 and March 2012 were enrolled in the study. Clinical symptoms, signs,
      laboratory examinations, treatment and outcomes were retrospectively studied.
      RESULTS: Anemia (96%), bleeding (68%), fever (68%) and hepatosplenomegaly (61%)
      were main clinical manifestaions in the 28 patients. Three cases (11%) converted
      into acute monocytic leukemia (M5), erythroleukemia (M6) or acute megakaryocytic
      leukemia (M7) one to two months later. Bone marrow proliferation mainly
      demonstrated as active or obviously active. One or two lineages of hematopoietic
      dysplasia were mostly observed in all 28 cases and obvious iron metabolism
      disorders were found in these patients. Cytogenetic abnormalities were detected
      in 45% of the 28 cases, most of which were numeral chromosome abnormalities. T
      cell, B cell and NK cell numbers decreased, Th cell numbers decreased, Ts cell
      numbers increased and Th /Ts inversed. Eight cases gave up treatment when
      confirmed. Of the 8 cases receiving symptomatic and supportive treatment alone,
      one was lost, one showed disease stability, and the remaining 6 cases showed
      disease progression. One patient who underwent induced differentiation and one
      who received hematopoietic therapy showed disease progression. Ten patients
      underwent chemotherapy. Two cases had no bone marrow remission after single agent
      chemotherapy. Of the 8 cases who underwent multi-drug combination chemotherapy, 4
      cases achieved partial or complete remission of bone marrow. CONCLUSIONS:
      Pediatric MDS is characterized by a lack of typical clinical manifestations, and
      a high rate of conversion to leukemia. Bone marrow proliferation is mainly active
      in children with MDS. One or two lineages of hematopoietic dysplasia is common.
      Among the cytogenetic abnormalities, numeral chromosome abnormalities are common.
      Obvious iron metabolism disorders and abnormal cellular immunity are found in
      children with MDS. Multi-drug combination chemotherapy appears to slow the course
      of the disease.

PMID- 23866270
TI  - [Correlation between serum vitamin D level and severity of community acquired
      pneumonia in young children].
AB  - OBJECTIVE: To study the correlation between serum vitamin D level and severity of
      community acquired pneumonia (CAP) in young children, and explore related risk
      factors for CAP. METHODS: One hundred and three children with CAP between October
      2011 and April 2012 were enrolled in the study, including 15 cases of severe CAP
      and 88 cases of mild CAP. Ninety healthy children were used as the control group.
      25-(OH)D(3) concentrations were measured by enzyme linked immunoassay. RESULTS:
      The mean vitamin D concentration in the severe CAP group was significantly lower
      than in the mild CAP and control groups (P < 0.01), and there was no significant
      difference between the mild CAP and control groups (P = 0.674). Premature birth
      and vitamin D < 50 nmol/L were risk factors for severe CAP in the multivariate
      analysis. CONCLUSIONS: Vitamin D deficiency might be associated with the severity
      of CAP in young children.

PMID- 23866271
TI  - [Mycoplasma pneumoniae infection and drug resistance in children: an analysis of
      1026 cases].
AB  - OBJECTIVE: To investigate the Mycoplasma pneumoniae (MP) infection and drug
      resistance in children with respiratory tract infection and to provide a rational
      basis for the clinical diagnosis and treatment of MP infection. METHODS: Throat
      swabs were collected from 3529 children with respiratory tract infection, who
      visited the pediatric outpatient department or received treatment in the
      pediatric ward of our hospital from September 2010 to September 2011. The swabs
      were cultured to detect MP. The drug sensitivity of MP to azithromycin,
      roxithromycin, erythromycin, acetylspiramycin and clarithromycin was evaluated.
      RESULTS: Of the 3529 children with respiratory tract infection, 1026 (29.07%)
      were MP-positive. There were cases of MP infection in all four seasons of the
      year but infection rates in summer and autumn were significantly higher than in
      spring and winter (P < 0.05). The infection rate in females was higher than in
      males (30.43% vs 28.32%; P > 0.05). The infection rate was negatively correlated
      with age in these children, and there were significant differences in the
      infection rate among all age groups (P < 0.05). For macrolide antibiotics
      suitable for children, the cultured MP developed the highest resistance to
      roxithromycin, followed by erythromycin, acetylspiramycin, clarithromycin, and
      azithromycin, with significant differences among them (P < 0.01). CONCLUSIONS: MP
      infection rate is very high among children with respiratory tract infection. The
      incidence of MP infection is relatively low among school-age children and
      children are more susceptible to MP infection in summer and autumn than in spring
      and winter. Throat swabs should be cultured and drug sensitivity tests should be
      performed as early as possible in children with respiratory tract infection, so
      that proper intervention can be undertaken in time to reduce drug-resistant
      strains of MP.

PMID- 23866272
TI  - [Application of continuous thoracic close drainage using central venous catheter
      in the treatment of tuberculous pleurisy in children].
AB  - OBJECTIVE: To study the clinical effect of continuous thoracic close drainage
      using central venous catheter instead of repeated thoracocentesis in the
      treatment of tuberculous pleurisy in children. METHODS: Thirty-nine children with
      tuberculous pleurisy, who received continuous thoracic close drainage using
      central venous catheter in addition to conventional antituberculous chemotherapy,
      were used as the observation group and 42 children with tuberculous pleurisy who
      underwent repeated thoracocentesis in addition to conventional antituberculous
      chemotherapy served as the control group. The two groups were compared in terms
      of time to pleural effusion absorption, improvement in pleural thickening, length
      of hospital stay, and puncture-related expenses. RESULTS: Compared with the
      control group, the observation group had significantly faster pleural effusion
      absorption (8 +/- 4 d vs 12 +/- 6 d; P < 0.01), significantly more improvement in
      pleural thickening (1.50 +/- 0.25 mm vs 3.10 +/- 0.30 mm; P < 0.05), a
      significantly shorter length of hospital stay (11 +/- 3 d vs 18 +/- 6 d; P <
      0.01), and significantly lower puncture-related expenses (269 +/- 24 yuan vs 475
      +/- 50 yuan; P < 0.05), as well as alleviated pain. CONCLUSIONS: Continuous
      thoracic close drainage using central venous catheter is superior to repeated
      thoracocentesis in the treatment of tuberculous pleurisy in children, and it
      holds promise for clinical application in pediatric patients.

PMID- 23866273
TI  - [Risk factors for intra-abdominal hypertension in children with sepsis].
AB  - OBJECTIVE: To study risk factors for the occurrence of intra-abdominal
      hypertension (IAH) in children with sepsis. METHODS: A nest case-control study
      was employed. According to intra-abdominal pressures (IAP) measured by
      cystometry, 119 children with sepsis were classified into normal IAP (control, n
      = 80) and IAH groups (n = 39). Risk factors for the occurrence of IAH were
      investigated by monovariable and multivariable logistic regression analysis.
      RESULTS: Monovariable analysis showed that there were significant differences in
      pediatric critical illness score (PCIS), procalcitonin (PCT) level, PaCO(2),
      blood lactate level, rates of intestinal or intra-abdominal infection, ascites,
      gastrointestinal dysfunction, mechanical ventilation, shock and multiple organ
      dysfunction syndrome (MODS) between the IAH and control groups (P < 0.05).
      Multivariable logistic regression analysis demonstrated that decreased PCIS,
      MODS, shock, gastrointestinal dysfunction and ascites were major risk factors for
      the occurrence of IAH. CONCLUSIONS: Children with sepsis who have decreased PCIS,
      MODS, shock, gastrointestinal dysfunction and ascites are at risk for the
      occurrence of IAH.

PMID- 23866274
TI  - [Meta-analysis of risk factors for childhood cerebral palsy during pregnancy].
AB  - OBJECTIVE: To investigate major risk factors for childhood cerebral palsy (CP)
      during pregnancy and to provide evidence for the prevention of CP. METHODS: Using
      the search terms of "cerebral palsy", "pregnancy", "risk factor", and "case
      control", a search was performed to collect case-control studies on the risk
      factors for childhood CP from 1998 to 2011. The obtained data were subjected to
      metaanalysis using fixed effects model and DersimonionLaird random effects model
      to quantitatively evaluate risk factors for childhood CP during pregnancy.
      RESULTS: Eighteen studies involving 11050 cases and 15941 controls were
      collected. The results of the multivariate analysis for risk factors of childhood
      CP during pregnancy were as follows: maternal age (>=35 years) (OR = 4.172, 95%CI
      = 1.670-10.426, P < 0.05), multiple pregnancy (OR = 8.402, 95% CI = 2.386-29.584,
      P < 0.05), medicine use in early pregnancy (OR = 3.974, 95% CI = 2.217-7.123, P <
      0.05), harmful environment (OR = 3.299, 95% CI = 1.058-10.289, P < 0.05),
      recurrent vaginal bleeding during pregnancy (OR = 4.736, 95% CI = 1.792-12.517, P
      < 0.05), pregnancy infectious diseases (OR = 1.238, 95%CI: 0.284-5.395, P >
      0.05), pregnancy induced hypertension (OR = 4.096, 95%CI: 2.246-7.469, P < 0.05),
      meat intake (OR = 1.436, 95%CI:0.382-5.393, P > 0.05), father smoking (OR =
      2.376, 95%CI: 0.801-7.049, P > 0.05). CONCLUSIONS: The major risk factors for
      childhood CP during pregnancy include advanced maternal age (>=35 years),
      multiple pregnancy, medicine use in early pregnancy, harmful environment,
      recurrent vaginal bleeding during pregnancy and pregnancy-induced hypertension.

PMID- 23866275
TI  - [Expression of urinary neutrophil gelatinase-associated lipocalin and its
      clinical significance in children with idiopathic nephrotic syndrome].
AB  - OBJECTIVE: To investigate the urinary neutrophil gelatinase-associated lipocalin
      (NGAL) concentration in children with idiopathic nephrotic syndrome (INS) and its
      clinical significance. METHODS: Thirty-four children newly diagnosed with INS
      received oral prednisone for 4 weeks. Patients whose urinary protein did not
      become negative were classified as steroid-resistant nephrotic syndrome (SRNS)
      group, while those whose urinary protein did become negative were classified as
      steroid-sensitive nephrotic syndrome (SSNS) group. Morning midstream urine
      specimens were collected from all patients before use of prednisone and after 1,
      2, 3, and 4 weeks of treatment with prednisone. Enzyme-linked immunosorbent assay
      was used to measure the urinary NGAL concentration. Meanwhile, urinary creatinine
      (Cr) concentration was measured, and urinary NGAL concentration in a single urine
      collection was adjusted according to the urinary Cr excretion. The two groups
      were compared in terms of urinary NGAL/Cr ratio. RESULTS: Compared with the SRNS
      group, the SSNS group had significantly decreased urinary NGAL/Cr ratios after 3
      and 4 weeks of prednisone treatment (P < 0.05). Compared with the SRNS group, the
      SSNS group had a significantly decreased urinary beta2-MG/Cr ratio after 4 weeks
      of prednisone treatment (P < 0.05). In both groups, urinary NGAL/Cr ratio was
      positively correlated with urinary protein/Cr ratio (r = 0.510, P < 0.01). The
      results of ROC curve analysis showed when diagnostic cut-off point of urinary
      NGAL/Cr was 0.043 by 3 weeks after treatment, sensitivity and specificity
      achieved 100% and 79.2% respectively. CONCLUSIONS: Urinary NGAL/Cr ratio remains
      high in children with SRNS, while this ratio decreases gradually during
      prednisone treatment in children with SSNS, and it falls ahead of urinary beta2
      MG/Cr ratio. These results suggest that dynamic monitoring of urinary NGAL/Cr
      ratio is useful for early judgment of response to prednisone in patients with
      INS.

PMID- 23866276
TI  - [Clinical application of single-balloon enteroscopy in children with small
      intestinal bleeding].
AB  - OBJECTIVE: To investigate the diagnostic value and safety of single-balloon
      electronic enteroscopy in children with small intestinal bleeding. METHODS:
      Seventy children with clinically suspected small intestinal bleeding, including
      38 males and 32 females aged 4-13 years, underwent single-balloon enteroscopy
      under general anesthesia. Twenty-six cases underwent the procedure through the
      mouth, 32 cases through the anus, and 12 cases through both. RESULTS: Of the 70
      children, 58 (83%) had small bowel disease according to the single-balloon
      enteroscopy results, including 24 cases of non-specific inflammation, 12 cases of
      allergic purpura, 8 cases of Crohn's disease, 8 cases of Meckel's diverticulum,
      and 6 cases of Peutz-Jeghers syndrome. CONCLUSIONS: Single-balloon enteroscopy is
      a safe, effective means for the diagnosis of small intestinal bleeding among
      children.

PMID- 23866277
TI  - [An epidemiological study of food intolerance in 2434 children].
AB  - OBJECTIVE: To investigate the epidemiological characteristics of intolerance to
      14 foods in children and the relationship between food intolerance and disease of
      various systems. METHODS: Serum samples of 2434 children with diseases were
      collected for food intolerance testing between January 2009 and October 2012.
      Allergen-specific IgG antibodies to 14 foods were detected using enzyme-linked
      immunosorbent assay. The children's intolerance to different foods and its
      relationship with age, sex and disease of various systems were analyzed. RESULTS:
      Among these children, positive rates of intolerance to milk and eggs were as high
      as 74.16% and 66.47% respectively, while positive rates of intolerance to chicken
      and pork were relatively low (0.29% and 0.21% respectively). The overall positive
      rates of food intolerance were 12.579% and 12.470% in males and females
      respectively. For infants, the highest intolerance rate was to milk; for
      preschool and school-age children, the highest intolerance rates were to milk and
      eggs respectively; for children in adolescence, the highest intolerance rate was
      to eggs. Among children with food intolerance involving single system, those with
      developmental abnormality or immune system disease had the highest overall
      positive rate of food intolerance. Children with double-system diseases had an
      overall positive rate of food intolerance as high as 13.393%. Among the children
      involving various systems, the positive rate of intolerance to milk and eggs were
      higher than other food. CONCLUSIONS: Factors influencing food intolerance in
      children include food categories and age. There may be a relationship between
      food intolerance and disease of various systems, and this is significant to the
      growth and development of children.

PMID- 23866278
TI  - [SRY gene-testing in the diagnosis of disorders of sex development among
      children].
AB  - OBJECTIVE: To investigate the value of direct sequencing of sex-determining
      region Y (SRY) gene, as well as peripheral blood karyotype analysis, in the
      diagnosis of disorders of sex development (DSD) among children and adolescents
      with ambiguous genitalia. METHODS: The karyotypes of 20 children and adolescents
      with ambiguous genitalia were determined by conventional G-banding analysis. PCR
      amplification was used to detect SRY gene in these patients, and direct
      sequencing was used to judge whether there was SRY gene mutation. RESULTS: Of the
      20 cases, 17 were positive for SRY gene, and 3 were negative for SRY gene. Direct
      sequencing revealed no SRY gene mutation in the positive cases, however karyotype
      analysis found 4 special karyotypes in these patients: 46, XY, del(Y) (q12)/45,
      X; 46, XY, add(Y) (p11); 46, XY, r(9); 46, XY, 9qh+. CONCLUSIONS: SRY gene
      detection can help determine the type of DSD among children and has the advantage
      of quick detection. Used together with G-banding analysis, it is helpful for
      primary diagnosis of DSD among children.

PMID- 23866279
TI  - [Unintentional injuries in children: an analysis of 924 cases].
AB  - OBJECTIVE: To investigate the causes of unintentional injuries in children and to
      provide reference for reducing the incidence of unintentional injuries in
      children. METHODS: A retrospective analysis was performed on the clinical data of
      924 children with unintentional injuries who were hospitalized in Zhongshan Boai
      Hospital from January 2008 to December 2010. RESULTS: Of the 924 cases, 26.4%
      suffered falls, which was the most common cause of injuries, 15.7% suffered burns
      and scalds, 14.0% were injured by foreign bodies, and 13.1% were injured in
      traffic accidents. Unintentional injuries occurred mainly among children aged 0-3
      years (67%). The proportion of cases in summer (July to September) was
      significantly higher than in any other season (P < 0.05), and burns were the
      common causes of injuries in summer. Home was the most common place where
      unintentional injuries occurred (36.9%). The incidence of traffic accidents was
      significantly higher in non-local children than in local children (P < 0.001). As
      for the parents' educational levels, the children whose parents had an education
      level below junior middle school accounted for the highest proportion of all
      cases of unintentional injury (45.5%). Injuried cases in rural areas accounted
      for a significantly higher percentage than in urban areas (P < 0.05).
      CONCLUSIONS: Falls are the principal cause of unintentional injuries in children.
      Young children (0-3 years) are most vulnerable to unintentional injuries.
      Unintentional injuries mostly occur at home. The incidence of traffic accidents
      is higher in non-local children than in local children. Parents' education levels
      are associated with the incidence of unintentional injuries. In order to reduce
      the incidence of unintentional injuries in children, preventive measures must be
      carried out, and safety education should be enhanced in consideration of
      children's age, sex and family background.

PMID- 23866280
TI  - [Association between MAOA-u VNTR polymorphism and its interaction with stressful
      life events and major depressive disorder in adolescents].
AB  - OBJECTIVE: To investigate whether the genetic polymorphism, upstream variable
      number of tandem repeats (uVNTR), in the monoamine oxidase A (MAOA) gene, is
      associated with major depressive disorder (MDD) in adolescents and to test
      whether there is gene-environment interaction between MAOA-uVNTR polymorphism and
      stressful life events (SLEs). METHODS: A total of 394 Chinese Han subjects,
      including 187 adolescent patients with MDD and 207 normal students as a control
      group, were included in the study. Genotyping was performed by SNaP-shot assay.
      SLEs in the previous 12 months were evaluated. The groups were compared in terms
      of the frequency distributions of MAOA-uVNTR genotypes and alleles using
      statistical software. The binary logistic regression model of gene-environment
      interaction was established to analyze the association of the gene-environment
      interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD. RESULTS:
      The distribution profiles of MAOA-u VNTR genotypes and alleles were not related
      to the onset of MDD, severity of depression, comorbid anxiety and suicidal
      ideation/behavior/attempt in adolescents. The gene-environment interaction
      between MAOA-u VNTR genotypes and SLEs was not associated with MDD in male or
      female adolescents. CONCLUSIONS: It is not proven that MAOA-u VNTR polymorphism
      is associated with adolescent MDD. There is also no gene-environment interaction
      between MAOA-u VNTR polymorphism and SLEs that is associated with adolescent MDD.

PMID- 23866281
TI  - [Early complications and treatment outcomes in test-tube premature infants].
AB  - OBJECTIVE: To study the incidence of early complications and treatment outcomes
      in premature infants conceived via test tube. METHODS: A retrospective analysis
      and comparison was conducted on the clinical data of 122 test-tube premature
      infants and 183 naturally conceived premature infants (control group), including
      maternal complications, birth conditions and early complications. RESULTS: There
      was no statistically significant difference in maternal complications between the
      two groups (P > 0.05). The incidence of respiratory distress syndrome (25.4% vs
      12.0%; P < 0.05) and malformations (3.3% vs 0%; P < 0.05) in the test-tube group
      was statistically higher than in the control group. The mortality rate in the
      test-tube group was statistically higher than in the control group (9.0% vs 2.2%;
      P < 0.05). CONCLUSIONS: Test-tube premature infants are more likely to suffer
      from respiratory distress syndrome and have higher incidences of congenital
      malformations and mortality. Asisted reproductive technique should therefore be
      chosen cautiously, and enhanced assessment and monitoring is needed during
      pregnancy.

PMID- 23866282
TI  - [The establishment of "two-step sequential filtration method" on the yield rate
      of purified islets in rats].
AB  - OBJECTIVE: To develop a simple, rapid and reliable method of purifying Sprague
      Dawley (SD) rat islets by sequential filtration through two cell strainers of
      different sizes and to evaluate the efficacy of the method. METHODS: Islets were
      isolated from 8 to 12-week-old clean grade Sprague-Dawley rat pancreases using
      the standard collagenase digestion procedure and purified with either the
      generally used Ficoll density gradient method or the innovative two-step
      sequential filtration method. The purity and vitality of the isolated islets were
      visualized and assessed with DTZ and AO/PI staining. Glucose stimulating tests
      were performed to assay cell activity, and immunohistochemical staining was used
      to evaluate the synthesis function of islet cells. RESULTS: The yield of islets
      in the two-step filtration method group was 782+/-115 IEQ per rat, which was
      significantly higher than in the conventional Ficoll density gradient method
      group (598 +/- 135 IEQ per rat, P < 0.01). Purity of the isolated islets in the
      two-step filtration method group was 90%-100% and vitality was over 95%. In the
      conventional Ficoll density gradient method group, islet purity was 65%-85% and
      vitality was 85%-95%. With regard to the high-sugar stimulation test in the two
      step filtration method group, insulin concentrations in islets cultured for 24
      hours were significantly higher than in those that were freshly purified (76.9 +/
      6.1 MUg/L vs 49.4 +/- 3.9 MUg/L; P < 0.01). CONCLUSIONS: A two-step sequential
      filtration method for rat islet purification was developed and the method was
      simple and reliable, with high islet vitality, purity and yield.

PMID- 23866283
TI  - [Effectiveness of anti-CD47 antibody and Ara-C combination targeting therapy
      NOD/SCID mouse of myeloid leukemia].
AB  - OBJECTIVE: To study the prognostic significance of CD47 in a NOD/SCID mouse model
      of acute myeloid leukemia (AML) and the best strategy for targeted therapy for
      this disease. METHODS: CD34(+)CD38(-) leukemia stem cells (LSCs) were separated
      and transplanted into NOD/SCID mice to establish a mouse model of acute monocytic
      leukemia (AMoL). Anti-human CD47 antibody, alone or combined with cytosine
      arabinoside (Ara-C), was used to treat the mice with AMoL for 7-14 days, and
      therapeutic efficacy was assessed. LSCs were cultured together with mouse
      macrophages in culture medium containing anti-CD47 or anti-CD45 monoclonal
      antibody for 2 hours, to observe the phagocytic ability of macrophages to LSCs.
      RESULTS: CD34(+)CD38(-) LSCs existed among THP-1 cells, with a content of about
      (0.12 +/- 0.06)%, and a mouse model of AML was successfully established after the
      purified CD34(+)CD38(-) LSCs (97.0% +/- 1.7%) were transplanted into NOD/SCID
      mice. The in vivo experiment showed that mice with AMoL had the most significant
      decrease in CD33(+)CD45(+) leukemia cells in peripheral blood and bone marrow and
      survived the longest after being treated with Ara-C (7 days) plus anti-CD47
      monoclonal antibody (14 days) (P < 0.01). After 2 hours of in vitro culture, the
      phagocytic index in the culture medium containing anti-CD47 monoclonal antibody
      was significantly higher than in the culture medium containing anti-CD45
      monoclonal antibody (76.9% +/- 12.2% vs 7.60% +/- 2.4%; P < 0.05). CONCLUSIONS:
      High expression of CD47 is an adverse prognostic factor in AML. Combination
      therapy with anti-CD47 monoclonal antibody and Ara-C can effectively eliminate
      leukemia cells and LSCs, demonstrating great clinical significance in curing AML.

PMID- 23866284
TI  - [Effect of peroxisome proliferator-activated receptor-gamma on proliferation of
      airway smooth muscle cells in mice with asthma].
AB  - OBJECTIVE: To investigate the effects of peroxisome proliferator-activated
      receptor-gamma (PPARgamma) agonist rosiglitazone on the expression of cyclin D1
      in lung tissue, and the proliferation of airway smooth muscle cells (ASMCs) in
      mice with bronchial asthma. METHODS: Thirty clean BALB/c mice were randomly
      divided into control group (n = 10), asthma group (n = 10), and rosiglitazone
      treatment group (n = 10). A mouse model of asthma was established by ovalbumin
      (OVA) sensitization and challenge. The treatment group received rosiglitazone (5
      mg/kg) by gavage 1 hour before each challenge and the control group received
      saline instead of OVA sensitization and challenge. Leukocytes and eosinophils in
      bronchoalveolar lavage fluid (BALF) were counted under a microscope. Airway
      structural changes were observed by hematoxylin-eosin staining. Protein and mRNA
      expression levels of cyclin D1 were measured by immunohistochemical staining and
      RT-PCR. Perimeter of the basement membrane (Pbm), total bronchial wall area
      (WAt), airway smooth muscle area (WAm), and number of nuclei in ASMCs (N) were
      determined using image analysis software, and WAt/Pbm, WAm/Pbm, and N/Pbm were
      calculated. RESULTS: Compared with the control group, the asthma group showed
      significant increases in the total number of leukocytes and percentage of
      eosinophils in BALF, as well as in the mRNA and protein expression of cyclin D1,
      but changes in these indices were significantly reduced in the rosiglitazone
      treatment group (P < 0.05). In addition, compared with the control group, the
      asthma group had significantly increased WAt/Pbm, WAm/Pbm, and N/Pbm, but
      rosiglitazone significantly decreased these ratios (P < 0.05). CONCLISONS:
      Rosiglitazone may delay the process of airway remodeling by inhibiting the
      proliferation of ASMCs, so it can be used for preventing and treating chronic
      asthma.

PMID- 23866285
TI  - [Preliminary study on the efficacy of irinotecan in the treatment of childhood
      relapsed hepatoblastoma].

PMID- 23866286
TI  - [Second HLA-identical related hematopoietic stem cells transplantation for
      juvenile myelomonocytic leukemia: one case report].

PMID- 23866287
TI  - [A case report of systemic lupus erythematosus complicated by lupus nephritis
      following histiocytic necrotizing lymphadenitis].

PMID- 23866288
TI  - [Mitochondrial disorders associated with mitochondrial respiratory chain complex
      V deficiency].
AB  - The mammalian mitochondrial ATP synthase, also as known as mitochondrial
      respiratory chain complex V, is a large protein complex located in the
      mitochondrial inner membrane, where it catalyzes ATP synthesis from ADP, Pi, and
      Mg2+ at the expense of an electrochemical gradient of protons generated by the
      electron transport chain. Complex V is composed of 2 functional domains F0 and
      F1. The clinical features of patients are significantly heterogeneous depending
      on the involved organs. Most patients with complex V deficiency had clinical
      onset in the neonatal period with severe brain damage or multi-organ failure
      resulting in a high mortality. Neuromuscular disorders, cardiomyopathy, lactic
      acidosis and 3-methylglutaconic aciduria are common findings. Complex V consists
      of 16 subunits encoded by both mitochondrial DNA and nuclear DNA. On MT-ATP6, MT
      ATP8, ATPAF2, TMEM70 and ATP5E gene of mitochondrial DNA, many mutations
      associated with Complex V deficiency have been identified. Here, the pathology,
      clinical features, diagnosis, treatment and molecular genetics of Complex V
      deficiency were summarized. 

PMID- 23866289
TI  - Cognitive functioning in obsessive-compulsive disorder: a meta-analysis.
AB  - BACKGROUND: Substantial empirical evidence has indicated impairment in the
      cognitive functioning of patients with obsessive-compulsive disorder (OCD)
      despite inconsistencies. Although several confounding factors have been
      investigated to explain the conflicting results, the findings remain mixed. This
      study aimed to investigate cognitive dysfunction in patients with OCD using a
      meta-analytic approach. METHOD: The PubMed database was searched between 1980 and
      October 2012, and reference lists of review papers were examined. A total of 221
      studies were identified, of which 88 studies met inclusion criteria.
      Neuropsychological performance and demographic and clinical variables were
      extracted from each study. RESULTS: Patients with OCD were significantly impaired
      in tasks that measured visuospatial memory, executive function, verbal memory and
      verbal fluency, whereas auditory attention was preserved in these individuals.
      The largest effect size was found in the ability to recall complex visual
      stimuli. Overall effect estimates were in the small to medium ranges for
      executive function, verbal memory and verbal fluency. The effects of potentially
      confounding factors including educational level, symptom severity, medication
      status and co-morbid disorders were not significant. CONCLUSIONS: Patients with
      OCD appear to have wide-ranging cognitive deficits, although their impairment is
      not so large in general. The different test forms and methods of testing may have
      influenced the performance of patients with OCD, indicating the need to select
      carefully the test forms and methods of testing used in future research. The
      effects of various confounding variables on cognitive functioning need to be
      investigated further and to be controlled before a definite conclusion can be
      made.

PMID- 23866290
TI  - What have we learnt from our mistakes?

PMID- 23866291
TI  - ECG measurements in end QRS notching and slurring.

PMID- 23866292
TI  - Do J waves constitute a syndrome?

PMID- 23866293
TI  - Detection of transient regional myocardial ischemia using body surface Delta map
      in patients referred for myocardial perfusion imaging--a pilot study.
AB  - BACKGROUND: The diagnosis of transient regional myocardial ischemia (TRMI) in
      patients presenting with stable chest pain is a challenge. Exercise Tolerance
      Test (ETT) is no longer recommended in most cases due to its flaws. Alternative
      tests are more expensive and less readily available. The BSM Delta map is an
      intuitive color display of digitally subtracted ST-segment shift derived from two
      80-electrode BSM recordings at baseline and at peak stress, and has shown promise
      as a tool for detection of TRMI. OBJECTIVES: The purpose of this pilot study was
      to assess the feasibility of BSM Delta map as a tool to detect TRMI using
      dobutamine stress ECG gated single-photon emission computed tomography myocardial
      perfusion imaging (MPI) as a reference. METHOD: Forty consecutive patients were
      recruited who were referred for MPI with a history of angina-like symptoms. The
      BSM Delta map was derived from two 80-electrode body surface mapping system
      recordings carried out simultaneously with MPI at (a) baseline and (b) peak
      dobutamine stress. Standard 12-lead ECGs were also recorded at the same time
      points. RESULTS: The mean patient age was 68+/-7.1years, and 52% (21/40) were
      female. Using MPI as the reference the sensitivity of BSM Delta map was 82%
      (9/11) and specificity was 86% (25/29) (95% CI 0.688-0.992), positive likelihood
      ratio 5.93 (95% CI 2.29-15), negative likelihood ratio 0.21 (95% CI 0.06-0.75).
      The sensitive of the 12-lead ECG was 36% (4/11) and specificity was 76% (22/29)
      (95% CI 0.356-0.767), positive likelihood ratio 1.51 (95% CI 0.55-4.15), negative
      likelihood ratio 0.84 (95% CI 0.51-1.37). BSM Delta map is more sensitive and
      specific (McNemar's chi-square test p=0.03 (95% CI, 0.448-0.924). The PPV and NPV
      for BSM Delta map were 69% (9/13) and 93% (25/27) respectively, compared with 36%
      (4/11) and 76% (22/29) for 12-lead ECG. CONCLUSION: This pilot study confirms the
      feasibility of using Delta map in this context and suggests that it has promising
      diagnostic accuracy and is superior to the 12-lead ECG. It could potentially
      represent a clinically suitable screening tool for TRMI in patients presenting
      with stable chest pain, since it is near patient and requires little specialist
      training for acquisition and interpretation. A larger clinical study is now
      required.

PMID- 23866294
TI  - Critical appraisal of the mechanism underlying J waves.

PMID- 23866295
TI  - Spectrum of ST amplitude: athletes and an ambulatory clinical population.
AB  - BACKGROUND AND PURPOSE: To augment data guiding thresholds for myocardial
      ischemia and cardiac risk, we studied resting ST amplitude in ambulatory patients
      and collegiate athletes. METHODS: We analyzed 4041 ECGs from ambulatory visits at
      the Veterans Affairs in Palo Alto, California from 1997 to 1999 and 1114
      screening ECGs from Stanford University athletes in 2007-2008. Using the PR
      interval as the isoelectric line and >95MUV and<-45MUV (visually equivalent to
      1mm and 0.5mm) to define ST elevation and depression, ST amplitude was measured
      at QRS-end. RESULTS: ST elevation was most prevalent in males, African Americans,
      and athletes (87% of male athletes in anterior leads). ST depression was rare in
      athletes and, among patients, associated with time to cardiovascular death in
      lateral leads (age-adjusted HR of 1.9, p<0.001). CONCLUSIONS: ST amplitude
      differs by gender, age, race, and athletic status, which should be considered
      when developing guidelines for ECG interpretation.

PMID- 23866296
TI  - Blood transfusion requirements for endoscopic sinonasal inverted papilloma
      resections.
AB  - BACKGROUND: Endoscopic resection of sinonasal Inverted Papilloma (SNIP) tumors
      has been shown to reduce intra-operative blood loss and recovery time compared to
      open approaches. The purpose of this study is to investigate the incidence and
      requirements of blood transfusion for endoscopic SNIP surgeries. METHODS: An
      individual retrospective cohort study of endoscopic SNIP surgeries over a 10-year
      period was performed. Age, sex, pre-existing co-morbidity, use of anti
      coagulants, tumor type and stage, time of surgery, estimated blood loss and the
      requirement for blood transfusion were recorded. RESULTS: 82 patients were
      included (57 males, 25 females). 4 (5%) Stage 1, 7 (8.5%) Stage 2, 62 (75.5%)
      Stage 3 and 9 (11%) Stage 4 SNIP tumors were identified according to the Krouse
      staging system. 3 (4%) patients required blood transfusion. 3 of the 9 (33%)
      Stage 4 tumors required blood transfusion. Stage 4 tumors were significantly
      associated with blood transfusion (p < 0.05). Higher staged tumors were
      associated with greater blood loss (p < 0.05) than lower staged cases. No other
      tumor stage required blood transfusion and no other pre-operative variable was
      associated with requirement for blood transfusion. CONCLUSION: Endoscopic SNIP
      resections rarely require blood transfusions. No pre-operative factor other than
      tumor stage is associated with the requirement for blood transfusion. We would
      therefore suggest that only Stage 4 SNIP tumors require pre-operative type and
      screen.

PMID- 23866297
TI  - Metastasis-associated protein 1 is a novel marker predicting survival and lymph
      nodes metastasis in cervical cancer.
AB  - Metastasis-associated gene 1 (MTA1), which is involved in tumor progression,
      metastasis, and angiogenesis, has been examined in several malignant tumors.
      However, the expression and the effect of MTA1 on human cervical cancer remain
      unknown. In this study, we investigated the level of MTA1 expression in cervical
      carcinoma and its clinical significance. By immunohistochemical staining, the
      correlation of MTA1 overexpression with clinical features and patient outcome was
      analyzed in 132 formalin-fixed, paraffin-embedded cervical cancer tissues. MTA1
      protein overexpression was detected in 73 (55.3%) of 132 patients. High levels of
      MTA1 protein were clearly correlated with histologic grade (P = .006), lymph node
      metastasis (P = .001), and recurrence (P = .016). Multivariate Cox analysis
      showed that MTA1 was an independent factor for overall survival (hazard ratio,
      3.486; 95% confidence interval [CI], 1.274-9.537; P = .015) and disease-free
      survival (hazard ratio, 3.373; 95% CI, 1.212-9.387; P = .020). Multivariate
      logistic regression analysis indicated that elevated MTA1 was strongly associated
      with lymph node metastasis (odds ratio, 3.879; 95% CI, 1.391-10.816; P = .010).
      Sensitivity and specificity were calculated as 81.25% and 53.0%, respectively.
      These findings suggest that MTA1 nuclear overexpression is associated with tumor
      progression and metastasis and thus support its clinical significance in future
      gene-targeted therapies, particularly the management of patients with cervical
      cancer. 

PMID- 23866298
TI  - A clinical and molecular study of artesunate + sulphadoxine-pyrimethamine in
      three districts of central and eastern India.
AB  - BACKGROUND: Artesunate + sulphadoxine-pyrimethamine (AS + SP) is recommended
      throughout India as the first-line treatment for uncomplicated falciparum
      malaria. Due to the presence of several eco-epidemiological zones of malaria and
      variable drug pressure, it is necessary to evaluate the efficacy of this
      combination in different regions of India. The objective of this study was to use
      clinical and molecular methods to monitor the efficacy of AS + SP in three
      diverse sites. METHODS: The study was undertaken in three high endemic sites of
      central and eastern India. Patients with uncomplicated falciparum malaria were
      enrolled and followed for 28 days. Molecular genotyping was conducted for
      merozoite surface protein (msp1 and msp2) to differentiate between re-infection
      and recrudescence and for the dhfr and dhps genes to monitor antifolate drug
      resistance. RESULTS: In all, 149 patients were enrolled at the three sites. The
      crude cure rates were 95.9%, 100%, and 100% in Ranchi, Keonjhar, and West Garo
      Hills respectively. PCR-corrected cure rates were 100% at all sites. In dhfr, 27%
      of isolates had triple mutations, while 46% isolates were double-mutants. The
      most prevalent mutation was S108N followed by C59R. 164 L mutation was observed
      in 43/126 (34%) isolates. In dhps, most (76%) of the isolates were wild-type.
      Only 2.5% (2/80) isolates showed double mutation. dhfr-dhps two locus mutation
      were observed in 16% (13/80) isolates. Parasite clearance time was not related
      with antifolate mutations. CONCLUSIONS: AS + SP combination therapy remained
      effective against falciparum malaria despite common mutations promoting
      resistance to antifolate drugs. Although the prevalence of double and triple
      mutations in dhfr was high, the prevalence of dhfr-dhps two locus mutations were
      low. Even isolates with dhfr triple and dhfr-dhps two locus mutations achieved
      adequate clinical and parasitological response.

PMID- 23866299
TI  - Non-alcoholic fatty liver disease (NAFLD): a tale of fat and sugar?
AB  - The global diffusion of the so-called Western diet, which is enriched in fat and
      carbohydrates, such as fructose, has been proposed to be an underlying cause of
      the increased prevalence of metabolic conditions, including non-alcoholic fatty
      liver disease (NAFLD). This Smart Card summarizes the main metabolic and hepatic
      histological features of rodent models fed with diets combining high fat and
      fructose. 

PMID- 23866301
TI  - The relationship between worry, rumination, and comorbidity: evidence for
      repetitive negative thinking as a transdiagnostic construct.
AB  - BACKGROUND: Repetitive negative thinking (RNT) increases vulnerability to
      multiple anxiety and depressive disorders and, as a common risk factor, elevated
      RNT may account for the high levels of comorbidity observed between emotional
      disorders. The aims of this study were to (a) compare two common forms of RNT
      (worry and rumination) across individuals with non-comorbid anxiety or depressive
      disorders, and (b) to examine the relationship between RNT and comorbidity.
      METHODS: A structured diagnostic interview and measures of rumination, worry,
      anxiety, and depression were completed by a large clinical sample with an anxiety
      disorder or depression (N=513) presenting at a community mental health clinic.
      RESULTS: Patients without (n=212) and with (n=301) comorbid diagnoses did not
      generally differ across the principal diagnosis groups (depression, generalised
      anxiety disorder, social anxiety disorder, panic disorder) on worry or
      rumination. As predicted, comorbidity was associated with a higher level of RNT.
      LIMITATIONS: Cross-sectional design precluded causal conclusions and findings may
      not generalize to excluded anxiety disorders. CONCLUSIONS: Consistent with the
      transdiagnostic hypothesis, RNT was associated with a range of anxiety disorders
      and depression and with comorbidity for those with a principal depressive
      disorder, supporting recent evidence that RNT is a transdiagnostic process. The
      presence of RNT, specifically worry and rumination, should be assessed and
      treated regardless of diagnostic profile. Future research may show that both pure
      and comorbid depressed or anxious patients receive incremental benefit from
      transdiagnostic protocols developed to treat core pathological processes of RNT
      traditionally associated with separate disorders.

PMID- 23866300
TI  - Effects of ziprasidone and olanzapine on body composition and metabolic
      parameters: an open-label comparative pilot study.
AB  - BACKGROUND: In contrast to olanzapine, ziprasidone has been reported to cause
      minimal or no weight gain. This study aimed to compare the effects of ziprasidone
      and olanzapine on weight, body composition, appetite, resting energy expenditure,
      substrate oxidation, and metabolic parameters in adults with schizophrenia or
      other psychotic disorders. METHODS: Twenty adults with schizophrenia or other
      psychotic disorders were randomized 1:1 to ziprasidone 20-160 mg/day or
      olanzapine 5-20 mg/day for 12 weeks. The mean doses during the 12-week study
      period were 109(range: 65-140) mg/day for ziprasidone and 11.6(range: 8.2-15.5)
      mg/day for olanzapine. Body weight, appetite, body composition, resting energy
      expenditure, and metabolic parameters were measured before and after drug
      treatment. Outcome measurements before and after medication were compared, and
      ziprasidone- and olanzapine-treated patients were compared. RESULTS: After 12
      weeks, olanzapine-treated patients showed significant weight gain, particularly
      fat gain, with increased low density lipoprotein-cholesterol and decreased high
      density lipoprotein-cholesterol concentrations. In contrast, ziprasidone-treated
      patients showed no significant weight gain with increased high density
      lipoprotein-cholesterol concentration. CONCLUSIONS: Ziprasidone was associated
      with a lower propensity for weight gain and central fat deposition than
      olanzapine. Studies in larger patient samples are required to confirm these
      results.

PMID- 23866302
TI  - Combined dexamethasone suppression-corticotrophin-releasing hormone stimulation
      test in medication-free major depression and healthy volunteers.
AB  - BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is dysfunctional in a
      subgroup of mood disorders. METHODS: We compared cortisol and adrenocorticotropic
      hormone (ACTH) responses in major depression and healthy volunteers to the
      combined dexamethasone suppression-corticotrophin-releasing hormone stimulation
      (DEX-CRH) test. Unlike other published studies, the study patients were
      medication-free and the healthy volunteers did not have first-degree relatives
      with a mood or psychotic disorder. Demographics, DSM-IV diagnoses and other
      clinical parameters were evaluated in major depressive disorder (MDD) and healthy
      control groups. Participants received an oral dose of 1.5mg dexamethasone at 11
      pm the day before CRH administration. On the following day, at 3 pm, 100 ug of
      ovine CRH was infused. Blood samples for determination of cortisol and ACTH were
      collected every 15 min from 3 pm to 4:15 pm. Cortisol and ACTH responses were
      calculated as areas under the curve. RESULTS: Controlling for age, baseline
      (i.e., post-dexamethasone) ACTH levels were higher in depressed patients compared
      to controls (p=0.01). There was a trend for higher ACTH responses in depressed
      patients compared to the control group (p=0.08). In depressed patients, cortisol
      and ACTH responses correlated positively with age, duration of illness and number
      of hospitalizations. LIMITATIONS: Because of the cross-sectional study design we
      can only evaluate the nature of potential HPA axis disturbances that were present
      in patients when they are acutely depressed. CONCLUSIONS: Feedback inhibition of
      ACTH secretion by cortisol is compromised in MDD, and this is independent of an
      age effect on the HPA axis function.

PMID- 23866303
TI  - Persistence of chronic major depression: a national prospective study.
AB  - BACKGROUND: Chronic major depressive disorder (CMDD) is highly prevalent and
      associated with high personal and societal cost. Identifying risk factors for
      persistence and remission of CMDD may help in developing more effective treatment
      and prevention interventions. METHODS: Prospective cohort study of individuals
      participating in the National Epidemiologic Survey on Alcohol and Related
      Conditions (Wave 1; n=43,093) and its 3-year follow-up (Wave 2; n=34,653) who met
      a diagnosis of CMDD at the Wave 1 assessment. RESULTS: Among the 504 respondents
      who met criteria for present CMDD at Wave 1, only 63 (11.52%) of them continued
      to meet criteria of CMDD. A history of childhood sexual abuse, earlier onset of
      MDD, presence of comorbidity and a history of treatment-seeking for depression
      predicted persistence of CMDD three years after the baseline evaluation.
      LIMITATIONS: Our sample is limited to adults, our follow-up period was only three
      years and the diagnosis of CMDD at baseline was retrospective. CONCLUSIONS: CMDD
      shows high rates of remission within three years of baseline assessment, although
      some specific risk factors predict a persistent course. Given the high personal
      and societal cost associated with CMDD, there is a need to develop and
      disseminate effective interventions for CMDD.

PMID- 23866304
TI  - Reduction of aggregation of beta-lactoglobulin during heating by dihydrolipoic
      acid.
AB  - Prevention of the heat-induced aggregation of beta-lactoglobulin (beta-Lg) would
      improve the heat stability of whey proteins. The effects of lipoic acid (LA, or
      thioctic acid), in both its oxidised and reduced form (dihydrolipoic acid, DHLA),
      on heat-induced unfolding and aggregation of beta-Lg were investigated. LA/DHLA
      was added to native beta-Lg and the mixture was heated at 70, 75, 80 or 85 
      degrees C for up to 30 min at pH 6.8. The samples were analysed by Polyacrylamide
      Gel Electrophoresis (PAGE) and Size-exclusion HPLC (SE-HPLC). LA was not as
      effective as DHLA in reducing the formation of aggregates of heated beta-Lg.
      Heating beta-Lg with DHLA resulted in formation of more beta-Lg monomers (due to
      dissociation of native dimers) and significantly less beta-Lg aggregates,
      compared with heating beta-Lg alone. The aggregates formed in the presence of
      DHLA were both covalently linked, via disulphide bonds, and non-covalently
      (hydrophobically) linked, but the amount of covalently linked aggregates was much
      less than when beta-Lg was heated alone. The results suggest that DHLA was able
      to partially trap the reactive beta-Lg monomer containing a free sulphydryl (-SH)
      group, by forming a 'modified monomer', and to prevent some sulphydryl-sulphydryl
      and sulphydryl-disulphide interactions that lead to the formation of covalently
      linked protein aggregates. The effects of DHLA were similar to those of N
      ethylmaleimide (NEM) and dithio(bis)-p-nitrobenzoate (DTNB). However, the
      advantage of using DHLA over NEM and DTNB to lessen aggregation of beta-Lg is
      that it is a food-grade compound which occurs naturally in milk. 

PMID- 23866305
TI  - Dabigatran versus warfarin under standard or pharmacogenetic-guided management
      for the prevention of stroke and systemic thromboembolism in patients with atrial
      fibrillation: a cost/utility analysis using an analytic decision model.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common form of heart arrhythmia
      and a leading cause of stroke and systemic embolism. Chronic anticoagulation is
      recommended for preventing those complications. Our study aimed to compare the
      cost/utility (CU) of three main anticoagulation options: 1) standard warfarin
      dosing (SD-W) 2) warfarin dosage under the guidance of CYP2C9 and VKORC1
      genotyping (GT-W) and 3) dabigatran 150 mg twice a day. METHODS: A Markov state
      transition model was built to simulate the expected C/U of dabigatran, SD-W and
      GT-W anticoagulation therapy for the prevention of stroke and systemic
      thromboembolism in patients with atrial fibrillation over a period of 5 years
      under the perspective of the public health care system. Model inputs were derived
      from extensive literature search and government's data bases. Outcomes considered
      were the number of total major events (thromboembolic and hemorrhagic events),
      total costs in Canadian dollars (1CAD$ = 1$US), total quality-adjusted life years
      (QALYs), costs/QALYs and incremental costs/QALYs gained (ICUR). RESULTS: Raw base
      case results show that SD-W has the lowest C/U ratio. However, the dabigatran
      option might be considered as an alternative, as its cost per additional QALY
      gained compared to SD-W is CAD $ 4 765, i.e. less than 50 000, the ICUR threshold
      generally accepted to adopt an intervention. At the same threshold, GT-W doesn't
      appear to be an alternative to SD-W. Our results were robust to one-way and multi
      way sensitivity analyses. CONCLUSION: SD-W has the lowest C/U ratio among the 3
      options. However, dabigatran might be considered as an alternative. GT-W is not
      C/U and should not currently be recommended for the routine anticoagulotherapy
      management of AF patients.

PMID- 23866306
TI  - Consistency of effect of ezetimibe/simvastatin compared with intensified lipid
      lowering treatment strategies in obese and non-obese diabetic subjects.
AB  - PURPOSE: This post hoc analysis assessed switching to ezetimibe/simvastatin 10/20
      mg vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20
      mg or switching to rosuvastatin 10 mg in subgroups of obese (BMI >=30 kg/m2) and
      non-obese (BMI <30 kg/m2) diabetic subjects. METHODS: This was a randomized,
      double-blind, 12-week study of adults 18-79 years with cardiovascular disease
      with low-density lipoprotein cholesterol (LDL-C) >=70 and <=160 mg/dl. Percent
      change in LDL-C and other lipids was estimated. RESULTS: In obese subjects (n =
      466), percent changes in LDL-C and most other lipids were greater with
      ezetimibe/simvastatin vs doubling the baseline statin dose or switching to
      rosuvastatin. In non-obese subjects (n = 342), percent changes in LDL-C, total
      cholesterol, non-HDL-C, Apo B and Apo A-I were greater with ezetimibe/simvastatin
      vs doubling the baseline statin dose or switching to rosuvastatin; and treatment
      with ezetimibe/simvastatin resulted in greater changes in triglycerides vs
      rosuvastatin and HDL-C vs doubling the baseline statin dose. The safety profiles
      were generally similar. CONCLUSIONS: Regardless of baseline obesity status,
      switching to ezetimibe/simvastatin was more effective at reducing LDL-C, total
      cholesterol, non-HDL-C, and Apo B vs doubling the baseline statin dose to
      simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg.

PMID- 23866307
TI  - Secondary neutron dose measurement for proton eye treatment using an eye snout
      with a borated neutron absorber.
AB  - BACKGROUND: We measured and assessed ways to reduce the secondary neutron dose
      from a system for proton eye treatment. METHODS: Proton beams of 60.30 MeV were
      delivered through an eye-treatment snout in passive scattering mode. Allyl
      diglycol carbonate (CR-39) etch detectors were used to measure the neutron dose
      in the external field at 0.00, 1.64, and 6.00 cm depths in a water phantom.
      Secondary neutron doses were measured and compared between those with and without
      a high-hydrogen-boron-containing block. In addition, the neutron energy and
      vertices distribution were obtained by using a Geant4 Monte Carlo simulation.
      RESULTS: The ratio of the maximum neutron dose equivalent to the proton absorbed
      dose (H(10)/D) at 2.00 cm from the beam field edge was 8.79 +/- 1.28 mSv/Gy. The
      ratio of the neutron dose equivalent to the proton absorbed dose with and without
      a high hydrogen-boron containing block was 0.63 +/- 0.06 to 1.15 +/- 0.13 mSv/Gy
      at 2.00 cm from the edge of the field at depths of 0.00, 1.64, and 6.00 cm.
      CONCLUSIONS: We found that the out-of-field secondary neutron dose in proton eye
      treatment with an eye snout is relatively small, and it can be further reduced by
      installing a borated neutron absorbing material.

PMID- 23866308
TI  - Neonatal human dermal fibroblasts immobilized in RGD-alginate induce
      angiogenesis.
AB  - Promoting angiogenesis in a damaged tissue is a major challenge for tissue
      regeneration. Recent findings in tissue engineering suggest that fibroblasts
      (FBs) play an important role in orchestrating the angiogenic process. Fibroblasts
      maintain the structural integrity of connective tissue by continuously secreting
      growth factors and extracellular matrix precursors, which are essential for
      endothelial cell (EC) adhesion and spreading, thus playing a crucial role in
      angiogenesis. We hypothesized that FBs immobilized in alginate gels grafted with
      the RGD peptidic sequence could influence the recruitment of ECs to improve
      vascularization. In this work, the modulation of immobilized human FBs within the
      3D synthetic extracellular matrix was assessed. Experiments using cocultures of
      ECs and FBs in indirect contact as well as angiogenic assays were performed to
      assess the influence of FBs immobilized in RGD-alginate in ECs' viability,
      stabilization, sprouting, and assembly into capillary-like structures. This study
      demonstrates the ability of FBs immobilized within RGD-alginate microspheres to
      modulate and support capillary-like structures' assembly. These findings indicate
      that the microenvironment created by these stromal cells in the scaffold
      modulates capillary morphogenesis, thus stimulating angiogenesis in situ and can
      potentially be used in regenerative medicine in clinical scenarios where
      vascularization is essential. 

PMID- 23866309
TI  - Oral bisphosphonate-related osteonecrosis of the jaws in dental implant patients:
      a case series.
AB  - Bisphosphonates have been associated with a serious adverse reaction known as
      bisphosphonate-related osteonecrosis of the jaws (BRONJ). The aim of this study
      was to describe its clinical characteristics in patients with dental implants who
      were taking bisphosphonates orally. We made a retrospective multicentre study in
      3 hospitals in Galicia, Spain. The medical records and clinical and radiological
      follow-up of the oral cavity were reviewed for those patients given
      bisphosphonates and diagnosed with BRONJ after the placement of dental implants
      within the previous 3 years. The series comprised 9 white patients (mean age 66
      years). The bisphosphonates were alendronate (n=6), ibandronate (n=2), and
      risedronate (n=1), and the most common indication was osteoporosis (n=7). The
      mean interval between the initiation of treatment and the onset of BRONJ lesions
      was 60 months. Most of the lesions were located around the mandibular implants
      (n=8). The mean interval between placement of dental implants and the onset of
      BRONJ was 34 (range 1-96) months. After treatment 7/9 patients recovered
      completely. The prevalence of BRONJ secondary to treatment with bisphosphonates
      taken orally after placement of dental implants may be higher than expected in a
      particular geographical region, but to date specific risk factors have not been
      identified. Clinical characteristics and the outcomes of treatment of lesions are
      similar to those seen in patients with BRONJ that is unrelated to placement of
      dental implants. 

PMID- 23866310
TI  - Ethyl acetate extract of germinated brown rice attenuates hydrogen peroxide
      induced oxidative stress in human SH-SY5Y neuroblastoma cells: role of anti
      apoptotic, pro-survival and antioxidant genes.
AB  - BACKGROUND: There are reports of improved metabolic outcomes due to consumption
      of germinated brown rice (GBR). Many of the functional effects of GBR can be
      linked to its high amounts of antioxidants. Interestingly, dietary components
      with high antioxidants have shown promise in the prevention of neurodegenerative
      diseases like Alzheimer's disease (AD). This effect of dietary components is
      mostly based on their ability to prevent apoptosis, which is believed to link
      oxidative damage to pathological changes in AD. In view of the rich antioxidant
      content of GBR, we studied its potential to modulate processes leading up to AD.
      METHODS: The total phenolic content and antioxidant capacity of the ethyl acetate
      extract of GBR were compared to that of brown rice (BR), and the cytotoxicity of
      both extracts were determined on human SH-SY5Y neuronal cells using 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay. Based on its
      higher antioxidant potentials, the effect of the GBR extract on morphological
      changes due to hydrogen peroxide (H2O2)-induced oxidative damage in human SH-SY5Y
      neuronal cells was examined using inverted light microscope and fluorescence
      microscope by means of acridine orange-propidium iodide (AO/PI) staining. Also,
      evaluation of the transcriptional regulation of antioxidant and apoptotic genes
      was carried out using Multiplex Gene Expression System. RESULTS: The ethyl
      acetate extract of GBR had higher total phenolic content and antioxidant capacity
      compared to BR. The cytotoxicity results showed that GBR extract did not cause
      any damage to the human SH-SY5Y neuronal cells at concentrations of up to 20 ppm,
      and the morphological analyses showed that the GBR extract (up to 10 ppm)
      prevented H2O2-induced apoptotic changes in the cells. Furthermore, multiplex
      gene expression analyses showed that the protection of the cells by the GBR
      extract was linked to its ability to induce transcriptional changes in
      antioxidant (SOD 1, SOD 2 and catalase) and apoptotic (AKT, NF-Kbeta, ERK1/2,
      JNK, p53 and p38 MAPK) genes that tended towards survival. CONCLUSIONS: Taken
      together, the results of our study showed that the ethyl acetate extract of GBR,
      with high antioxidant potentials, could prevent H2O2-induced oxidative damage in
      SH-SY5Y cells. The potential of GBR and its neuroprotective mechanism in
      ameliorating oxidative stress-related cytotoxicity is therefore worth exploring
      further.

PMID- 23866311
TI  - A cluster randomized controlled trial of the be the best you can be intervention:
      effects on the psychological and physical well-being of school children.
AB  - BACKGROUND: The 'Be the Best You Can Be' (BtBYCB) program is a school-based
      intervention designed to foster positive physical, psychological, and social
      development via empowering young people to take ownership over their own personal
      development. The aim of this work is to determine the effectiveness of the BtBYCB
      program on (i) pupils' well-being, self-perceptions, self-esteem, aspirations,
      and learning strategies; and (ii) changes in modifiable health-risk behaviors
      (i.e., physical activity, diet, smoking, and alcohol consumption).
      METHODS/DESIGN: A two-arm cluster randomized controlled trial employing a wait
      list control plus qualitative and mixed-method evaluations was used. Participants
      were school pupils from Years 7 and 8 (aged 11-13 years). Ten schools located in
      southwest England were randomly allocated to receive the BtBYCB intervention (n =
      5 schools; 711 pupils) or a control condition (i.e., usual Personal, Social, and
      Health Education classes) (n = 5 schools; 622 pupils). Participants in the
      intervention condition received a program consisting of (i) a talk from an
      Olympian/Paralympian; (ii) 11 one-hour teacher-led PSHE classroom sessions in
      which pupils identified their aspirations, values, and interests and explored and
      acted on these via activities such as personal development planning, goal
      setting, and peer-mentoring; and (iii) participated in a celebration event (e.g.,
      second visit from Olympian/Paralympian and short individual presentations). Data
      were collected at baseline, post-intervention, and at 3-month follow-up.Focus
      groups (pupils and teachers) and individual interviews (headteachers) were
      conducted in the 5 intervention schools to (i) gain an in-depth understanding of
      mechanisms of change; (ii) explore ways in which the participants' motivation and
      engagement could be enhanced, and (iii) elicit user-feedback pertaining to how
      the program, content, and appeal could be improved.A mixed-method approach was
      used to describe and explain the differing experiences of particular groupings
      within and across the intervention schools; i.e., those for whom the program was
      effective, those that experienced little, if any change, and those for whom the
      program led to an inverse effect. DISCUSSION: The findings of this work will
      provide insight into the effectiveness of an innovative and child-centered
      program. The research will inform improvements to the BtBYCB program as well as
      other interventions targeting child/youth health and wellness. TRIAL
      REGISTRATION: The trial is registered as Current Controlled Trials
      ISRCTN99443695.

PMID- 23866312
TI  - M-CSF increases proliferation and phagocytosis while modulating receptor and
      transcription factor expression in adult human microglia.
AB  - BACKGROUND: Microglia are the primary immune cells of the brain whose phenotype
      largely depends on their surrounding micro-environment. Microglia respond to a
      multitude of soluble molecules produced by a variety of brain cells. Macrophage
      colony-stimulating factor (M-CSF) is a cytokine found in the brain whose receptor
      is expressed by microglia. Previous studies suggest a critical role for M-CSF in
      brain development and normal functioning as well as in several disease processes
      involving neuroinflammation. METHODS: Using biopsy tissue from patients with
      intractable temporal epilepsy and autopsy tissue, we cultured primary adult human
      microglia to investigate their response to M-CSF. Mixed glial cultures were
      treated with 25 ng/ml M-CSF for 96 hours. Proliferation and phagocytosis assays,
      and high through-put immunocytochemistry, microscopy and image analysis were
      performed to investigate microglial phenotype and function. RESULTS: We found
      that the phenotype of primary adult human microglia was markedly changed
      following exposure to M-CSF. A greater number of microglia were present in the M
      CSF- treated cultures as the percentage of proliferating (BrdU and Ki67-positive)
      microglia was greatly increased. A number of changes in protein expression
      occurred following M-CSF treatment, including increased transcription factors
      PU.1 and C/EBPbeta, increased DAP12 adaptor protein, increased M-CSF receptor
      (CSF-1R) and IGF-1 receptor, and reduced HLA-DP, DQ, DR antigen presentation
      protein. Furthermore, a distinct morphological change was observed with
      elongation of microglial processes. These changes in phenotype were accompanied
      by a functional increase in phagocytosis of Abeta1-42 peptide. CONCLUSIONS: We
      show here that the cytokine M-CSF dramatically influences the phenotype of adult
      human microglia. These results pave the way for future investigation of M-CSF
      related targets for human therapeutic benefit.

PMID- 23866313
TI  - Plasmodium vivax and Mansonella ozzardi co-infection in north-western Argentina.
AB  - A case of co-infection with Plasmodium vivax and Mansonella ozzardi was detected
      in a blood sample from a person who had shown symptoms of malaria and lived in a
      city that was close to the Argentina/Bolivia border. The case was detected during
      a random revision of thick and thin smears from patients diagnosed with malaria
      from various towns and cities located in north-western Argentina between 1983 and
      2001. Trophozoites of P. vivax were observed in the thin blood smear along with
      M. ozzardi microfilaria (larval form), which presented a long, slender, pointed
      anucleate tail and the absence of the sheath. This last characteristic is shared
      with Mansonella perstans, Mansonella streptocerca and Onchocerca volvulus. More
      rigorously controlled studies to detect other co-infection cases in the area as
      well as the possibility of importation from Bolivia into Argentina are currently
      ongoing. The relationship between the malaria parasite and microfilaria, the
      potential effect of malaria treatment on the development of M. ozzardi, and the
      possible impact of this microfilaria on the immunity of a person against P. vivax
      are all still unknown. This contribution constitutes a point of focus for future
      studies involving the interaction between the parasites and the potential risk
      that humans are exposed to. 

PMID- 23866314
TI  - Red yeast rice lowers cholesterol in physicians - a double blind, placebo
      controlled randomized trial.
AB  - BACKGROUND: In recent years, red yeast rice (RYR) supplements have been marketed
      aggressively as a natural way to lower cholesterol; however, the large majority
      of commercially available products have not been studied according to current
      research standards. METHODS: In a double blind placebo controlled randomized
      trial, 52 physicians and their spouses with a total cholesterol level of > 200
      mg/dL were randomly allocated to receive a RYR extract or placebo for 8 weeks. As
      a primary outcome measure, we compared the before-after difference in lipid
      levels between both groups. As secondary outcome measures we looked at side
      effects, CK elevation and a change in cardiovascular risk. RESULTS: LDL (low
      density lipoprotein) cholesterol was lowered with 36 mg/dL (22%) and total
      cholesterol with 37 mg/dL (15%) in the intervention group. This result was
      statistically significant as compared to the control group, in which no reduction
      in total cholesterol and LDL was observed (p < 0.001). There was no marked
      difference in CK (creatine kinase)-elevation or reported side-effects between
      study groups. In 5/31 participants in the intervention group, the lipid lowering
      effect resulted in lower cardiovascular risk as measured with SCORE (Systematic
      COronary Risk Evaluation). CONCLUSIONS: The RYR formulation under study was
      effective in lowering cholesterol and LDL cholesterol in this study population.
      RYR therapy may be an attractive and relatively well studied alternative in
      patients who are intolerant for statins or who have objections against
      pharmacological lipid lowering. However, consumers need to be warned that the
      actual content of commercially available preparations is not assured by
      governmental regulations, which raises effectiveness and safety issues. TRIAL
      REGISTRATION: Clinicaltrials.gov, nr: NCT01558050.

PMID- 23866316
TI  - Concomitant microfilaria and malaria infection.

PMID- 23866315
TI  - Altered reward processing in the orbitofrontal cortex and hippocampus in healthy
      first-degree relatives of patients with depression.
AB  - BACKGROUND: Healthy first-degree relatives of patients with major depression
      (rMD+) show brain structure and functional response anomalies and have elevated
      risk for developing depression, a disorder linked to abnormal serotonergic
      neurotransmission and reward processing. METHOD: In a two-step functional
      magnetic resonance imaging (fMRI) investigation, we first evaluated whether
      positive and negative monetary outcomes were differentially processed by rMD+
      individuals compared to healthy first-degree relatives of control probands (rMD
      ). Second, in a double-blinded placebo-controlled randomized trial we
      investigated whether a 4-week intervention with the selective serotonergic
      reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and
      brain responses of the rMD+ individuals. RESULTS: Negative outcomes increased the
      probability of risk-averse choices in the subsequent trial in rMD+ but not in rMD
      individuals. The orbitofrontal cortex (OFC) displayed a stronger neural response
      when subjects missed a large reward after a low-risk choice in the rMD+ group
      compared to the rMD- group. The enhanced orbitofrontal response to negative
      outcomes was reversed following escitalopram intervention compared to placebo.
      Conversely, for positive outcomes, the left hippocampus showed attenuated
      response to high wins in the rMD+ compared to the rMD- group. The SSRI
      intervention reinforced the hippocampal response to large wins. A subsequent
      structural analysis revealed that the abnormal neural responses were not
      accounted for by changes in gray matter density in rMD+ individuals. CONCLUSIONS:
      Our study in first-degree relatives of depressive patients showed abnormal brain
      responses to aversive and rewarding outcomes in regions known to be dysfunctional
      in depression. We further confirmed the reversal of these aberrant activations
      with SSRI intervention.

PMID- 23866317
TI  - Routine surgery in addition to chemotherapy for treating spinal tuberculosis.
AB  - BACKGROUND: Tuberculosis is generally curable with chemotherapy, but there is
      controversy in the literature about the need for surgical intervention in the one
      to two per cent of people with tuberculosis of the spine. OBJECTIVES: To compare
      chemotherapy plus surgery with chemotherapy alone for treating people diagnosed
      with active tuberculosis of the spine. SEARCH METHODS: We searched the Cochrane
      Infectious Diseases Group Specialized Register (February 2010), CENTRAL (The
      Cochrane Library 2010,Issue 1), MEDLINE (1966 to February 2010), EMBASE (1974 to
      February 2010), LILACS (1982 to February 2010), conference proceedings, and
      reference lists. A search update in November 2012 revealed no new studies.
      SELECTION CRITERIA: Randomized controlled trials with at least one year follow up
      that compared chemotherapy plus surgery with chemotherapy alone for treating
      active tuberculosis of the thoracic and/or lumbar spine. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial eligibility, methodological
      quality, and extracted data.We analysed data using odds ratio with 95% confidence
      intervals. MAIN RESULTS: Two randomized controlled trials (331 participants) met
      the inclusion criteria. They were conducted in the 1970s and 1980s with follow-up
      reports available after 18 months, three years, and five years; one trial also
      reported 10 years follow up. Completeness of follow up varied at the different
      time points, with less than 80% of participants available for analysis at several
      time points. There was no statistically significant difference for any of the
      outcome measures: kyphosis angle, neurological deficit (none went on to develop
      this), bony fusion, absence of spinal tuberculosis, death from any cause,
      activity level regained, change of allocated treatment, or bone loss. Neither
      trial reported on pain. Of the 130 participants allocated to chemotherapy only,
      12 had a neurological deficit and five needed a decompression operation. One
      trial suggested that an initial kyphosis angle greater than 30 degrees  is likely
      to deteriorate, especially in children. AUTHORS' CONCLUSIONS: The two included
      trials had too few participants to be able to say whether routine surgery might
      help. Although current medication and operative techniques are now far more
      advanced, these results indicate that routine surgery cannot be recommended
      unless within the context of a large, well-conducted randomized controlled trial.
      Clinicians may judge that surgery may be clinically indicated in some groups of
      patients. Future studies need to address these topics as well as the patient's
      view of their disease and treatment.

PMID- 23866318
TI  - Sponge versus diaphragm for contraception.
AB  - BACKGROUND: The contraceptive vaginal sponge was developed as an alternative to
      the contraceptive diaphragm. The sponge, made of polyurethane impregnated with
      nonoxynol-9 (1g), releases 125 mg of the spermicide over 24 hours of use. Unlike
      the diaphragm, the sponge can be used for more than one coital act within 24
      hours without the insertion of additional spermicide, and the sponge does not
      require fitting or a prescription from a physician. How the sponge compares with
      the diaphragm in terms of efficacy and continuation is not clear. OBJECTIVES: To
      compare the efficacy and continuation rates of the sponge with the diaphragm
      (used with nonoxynol-9). Our a priori hypothesis was that the sponge would have
      higher rates for failure and discontinuation than the diaphragm. SEARCH METHODS:
      In April 2013, we searched the computerized databases MEDLINE, POPLINE, LILACS,
      CENTRAL, ClinicalTrials.gov and ICTRP.Earlier searches also included EMBASE. For
      the initial review, we searched the reference lists of relevant articles and book
      chapters.We also contacted investigators involved with the identified trials for
      other published or unpublished trials. SELECTION CRITERIA: We included randomized
      controlled trials comparing the vaginal contraceptive sponge (Today; Collatex)
      with any diaphragm used with nonoxynol-9 to prevent pregnancy. DATA COLLECTION
      AND ANALYSIS: We examined the studies identified through the literature searches
      for possible inclusion and evaluated their methodological quality using the
      Cochrane guidelines. We entered data into RevMan and calculated Peto odds ratios
      for overall pregnancy and 12-month discontinuation using numbers of women as the
      denominator. We also abstracted 12-month cumulative life-table ratios for these
      same outcomes but were unable to aggregate these data. MAIN RESULTS: Two trials
      met the inclusion criteria. The sponge was significantly less effective in both
      trials in preventing overall pregnancy than was the diaphragm. In the larger USA
      trial, the 12-month cumulative life-table termination rates per 100 women for
      overall pregnancy were 17.4 for the sponge and 12.8 for the diaphragm. The rates
      were 24.5 for the sponge and 10.9 for the diaphragm in the UK trial.Similarly,
      discontinuation rates at 12 months were higher with the sponge than with the
      diaphragm (Odds ratio 1.31; 95% CI 1.07 to 1.59). Allergic-type reactions were
      more common with the sponge, although discontinuation for discomfort differed in
      the two trials.No new trials have been identified since the initial review.
      AUTHORS' CONCLUSIONS: The sponge was less effective than the diaphragm in
      preventing pregnancy.Discontinuation rates were higher at 12 months as well.Other
      randomized controlled trials will be needed to resolve the potential role of
      spermicides in preventing sexually transmitted infections or in causing adverse
      effects

PMID- 23866319
TI  - [QT drugs--what is the clinical significance?].

PMID- 23866320
TI  - [Uncertainty about the duration of HPV vaccine immunogenicity in boys].

PMID- 23866321
TI  - [Risk of sudden cardiac death induced by QT drugs].

PMID- 23866322
TI  - [Accreditation in general practice].

PMID- 23866323
TI  - [IKAS: Good for the patients].

PMID- 23866324
TI  - Focus on mapping the brain.

PMID- 23866326
TI  - Why mapping the brain matters.

PMID- 23866327
TI  - The author file: Joshua Sanes.

PMID- 23866325
TI  - From the connectome to brain function.
AB  - In this Historical Perspective, we ask what information is needed beyond
      connectivity diagrams to understand the function of nervous systems. Informed by
      invertebrate circuits whose connectivities are known, we highlight the importance
      of neuronal dynamics and neuromodulation, and the existence of parallel circuits.
      The vertebrate retina has these features in common with invertebrate circuits,
      suggesting that they are general across animals. Comparisons across these systems
      suggest approaches to study the functional organization of large circuits based
      on existing knowledge of small circuits.

PMID- 23866328
TI  - Points of view: plotting symbols.

PMID- 23866329
TI  - Changing one cell type into another.

PMID- 23866330
TI  - Complex logic in a single layer.

PMID- 23866331
TI  - Crystallography without crystals.

PMID- 23866332
TI  - Dream stream decoded.

PMID- 23866333
TI  - Nano-suiting up for SEM.

PMID- 23866334
TI  - Dynamics of DNA demethylation.

PMID- 23866335
TI  - Magnetic field imaging and more.

PMID- 23866336
TI  - Improved tools for the Brainbow toolbox.
AB  - In the transgenic multicolor labeling strategy called 'Brainbow', Cre-loxP
      recombination is used to create a stochastic choice of expression among
      fluorescent proteins, resulting in the indelible marking of mouse neurons with
      multiple distinct colors. This method has been adapted to non-neuronal cells in
      mice and to neurons in fish and flies, but its full potential has yet to be
      realized in the mouse brain. Here we present several lines of mice that overcome
      limitations of the initial lines, and we report an adaptation of the method for
      use in adeno-associated viral vectors. We also provide technical advice about how
      best to image Brainbow-expressing tissue.

PMID- 23866337
TI  - Retraction notice to Expression and function of toll-like receptor on T cells
      [Cellular Immunology 233 (2005) 85-89].

PMID- 23866338
TI  - Pharmacoresistance in epilepsy. Proceedings of the 2nd Halifax International
      Epilepsy Conference & Retreat. September 21-22, 2012. Halifax, Nova Scotia,
      Canada.

PMID- 23866339
TI  - Proceedings of the Fifth National Scientific Meeting of the Social and Behavioral
      Sciences Research Network (SBSRN). Atlanta, Georgia, USA. October 8-9, 2010.

PMID- 23866341
TI  - Nurse education: strike a balance.

PMID- 23866340
TI  - Safe staffing to prevent lessons of the past.

PMID- 23866342
TI  - Leaving in despair.

PMID- 23866343
TI  - Recovery from addiction: making the successful transition back to health.

PMID- 23866344
TI  - Mirage or reality?

PMID- 23866345
TI  - Pazopanib and soft-tissue sarcomas. Too toxic.
AB  - Soft-tissue sarcomas are rare tumours of mesenchymal origin. Patients with
      metastatic disease have a median survival of about 10 months. Doxorubicin, an
      anthracycline, is often used to reduce tumour volume, but it does not prolong
      overall survival. Pazopanib, a multiple tyrosine kinase inhibitor already
      marketed for kidney cancer, is now licensed for the treatment of certain
      metastatic soft-tissue sarcomas when chemotherapy fails or when the disease
      progresses despite adjuvant or neoadjuvant therapy. Clinical evaluation of
      pazopanib in this setting is based on a double-blind, randomised, placebo
      controlled trial in 369 patients whose tumours had progressed despite at least
      one line of chemotherapy, based on an anthracycline. In this trial, pazopanib did
      not provide a statistically significant increase in overall survival. The median
      survival time was about 12 months. A statistically significant increase in median
      progression-free survival was observed (4.6 versus 1.6 months, an increase of 3
      months), based mainly on radiological criteria. Pazopanib did not improve quality
      of life. The adverse effect profile includes cardiovascular, gastrointestinal and
      hepatic disorders, and palmoplantar erythrodysaesthesia. Serious adverse effects
      are frequent. Other life-threatening adverse effects observed in patients with
      soft-tissue sarcoma include pneumothorax (especially in case of pulmonary
      metastasis), heart failure, venous thrombosis, pulmonary embolism and
      hypothyroidism. In practice, given its lack of any proven impact on overall
      survival and its excessive toxicity, the use of pazopanib is not justified. It is
      better to focus on appropriate symptomatic care in order to preserve these
      patients' quality of life.

PMID- 23866346
TI  - INN common stem: -anib.

PMID- 23866347
TI  - Eplerenone and chronic heart failure. No comparison with spironolactone.
AB  - Still no randomised controlled trials versus spironolactone, but a prematurely
      terminated placebo-controlled trial with 2737 patients.

PMID- 23866348
TI  - Patients' interest overlooked.

PMID- 23866349
TI  - Belimumab. No tangible efficacy but a risk of immunosuppression.
AB  - Systemic lupus erythematosus is a chronic inflammatory autoimmune disease with
      variable clinical manifestations, mainly affecting women between the ages of 16
      and 55 years. It can be life-threatening, especially when renal or neurological
      involvement occurs. Belimumab (Benlysta", Glaxo-SmithKline) is an
      immunosuppressant monoclonal antibody that inhibits B cell differentiation into
      antibody-producing plasma cells. Belimumab is authorised in the European Union
      for the treatment of adults with autoantibody-positive systemic lupus
      erythematosus when the disease remains highly active despite "standard" therapy,
      usually comprising a corticosteroid or another immunosuppressant. In this
      setting, two double-blind randomised placebo-controlled trials compared two doses
      of belimumab (1 or 10 mg/kg), given every 2 weeks and then every 4 weeks, in
      addition to "standard" treatment, in a total of 1684 adult patients. Patients
      with severe renal or central nervous system involvement were excluded. After 52
      weeks the proportion of patients who "responded" to add-on therapy was about 10%
      higher with belimumab (10 mg/kg) than with placebo, a statistically significant
      difference. However, this advantage did not persist in one trial that was
      continued until 76 weeks. Belimumab had no statistically significant benefit in
      terms of corticosteroid use, time to exacerbations, or quality of life. In a
      combined analysis of the two trials, the difference in the response rate was
      greater in the prospectively defined subgroup of patients with "highly active"
      disease (63.2% with belimumab 10 mg/kg versus 44.3% with placebo; p<0.0001).
      Adverse reactions can occur during belimumab infusion, including severe and
      sometimes late-onset hypersensitivity reactions. The risk of infections
      (particularly opportunistic infections) and cancer is poorly documented.
      Belimumab also carries a risk of additional immunosuppression when used in
      combination with other immunosuppressive drugs. In early 2013, given the lack of
      any proven benefit and the uncertainties surrounding its adverse effects,
      belimumab add-on therapy simply complicates the treatment of systemic lupus
      erythematosus and should not be used.

PMID- 23866350
TI  - Strontium ranelate for osteoporosis in men. More dangerous than beneficial.
AB  - Increasingly numerous and potentially serious adverse effects have been reported
      since market release. There was no preventive effect on symptomatic fractures in
      a trial with 261 men.

PMID- 23866351
TI  - Ethinylestradiol + cyproterone. Good riddance.

PMID- 23866352
TI  - Calcium supplementation: cardiovascular risk?
AB  - Adequate dietary calcium intake and appropriate sunlight exposure ensuring
      adequate vitamin D availability are basic measures for the prevention of
      osteoporosis. Calcium and vitamin D supplementation increases bone density.
      Vitamin D plus calcium supplementation prevents hip fractures and other
      nonvertebral fractures in institutionalised persons 70 years of age or older. A
      meta-analysis of clinical trials showed an increase in myocardial infarction in
      patients taking calcium supplementation alone, with a relative risk of about 1.3.
      Epidemiological studies have not shown an increase in the cardiovascular risk.
      Conflicting results have also been reported in postmenopausal women taking both
      calcium and vitamin D. In an epidemiological study, hypercalcaemia was associated
      with increased mortality, particularly cardiovascular mortality. In practice,
      caution dictates that not all patients should routinely take calcium and vitamin
      D supplements. When calcium supplements are nonetheless used, the dose should be
      adjusted to dietary intake in order to avoid hypercalcaemia.

PMID- 23866353
TI  - Phosphate-containing eye drops: corneal opacity.
AB  - Harm-benefit balance of eye drops should be reviewed regularly.

PMID- 23866354
TI  - Leflunomide: psoriasis, lupus.

PMID- 23866355
TI  - Voriconazole: skeletal fluorosis.

PMID- 23866356
TI  - Tetrazepam: Lyell's syndrome and other serious disorders.

PMID- 23866357
TI  - Choose warfarin.

PMID- 23866359
TI  - Severe COPD: oxygen prolongs survival.
AB  - More than 15 hours of oxygen per day: prolongs survival.

PMID- 23866358
TI  - Bleeding with dabigatran, rivaroxaban, apixaban. No antidote, and little clinical
      experience.
AB  - Dabigatran, rivaroxaban and apixaban are oral anticoagulants used to prevent or
      treat thrombosis in a variety of situations. Like all anticoagulants, these drugs
      can provoke bleeding. How should patients be managed if bleeding occurs during
      dabigatran, rivaroxaban or apixaban therapy? How can the risk of bleeding be
      reduced in patients who require surgery or other invasive procedures? To answer
      these questions, we reviewed the available literature, using the standard
      Prescrire methodology. In clinical trials, warfarin, enoxaparin, dabigatran,
      rivaroxaban and apixaban were associated with a similar frequency of severe
      bleeding. Numerous reports of severe bleeding associated with dabigatran have
      been recorded since this drug was first marketed. Some situations are associated
      with a particularly high bleeding risk, including: even mild renal failure,
      advanced age, extremes in body weight and drug-drug interactions, particularly
      with antiplatelet agents (including aspirin), nonsteroidal antiinflammatory
      drugs, and many drugs used in cardiovascular indications. In patients treated
      with dabigatran, rivaroxaban or apixaban, changes in the INR (international
      normalised ratio) and activated partial thromboplastin time (aPTT) do not
      correlate with the dose. In early 2013, there is still no routine coagulation
      test suitable for monitoring these patients; specific tests are only available in
      specialised laboratories. In early 2013 there is no antidote for dabigatran,
      rivaroxaban or apixaban, nor any specific treatment with proven efficacy for
      severe bleeding linked to these drugs. Recommendations on the management of
      bleeding in this setting are based mainly on pharmacological parameters and on
      scarce experimen-Haemodialysis reduces the plasma concentration of dabigatran,
      while rivaroxaban and apixaban cannot be eliminated by dialysis. Prothrombin
      complex concentrates and recombinant activated factor VII seem to have little or
      no efficacy, and they carry a poorly documented risk of thrombosis. For patients
      undergoing surgery or other invasive procedures, clinical practice guidelines are
      primarily based on pharmacokinetic parameters and on extrapolation of data on
      vitamin K antagonists. The decision on whether or not to discontinue
      anticoagulation before the procedure mainly depends on the likely risk of
      bleeding. In patients at high risk of thrombosis, heparin can be proposed when
      the anticoagulant is withdrawn. In early 2013, difficulties in the management of
      bleeding and of situations in which there is a risk of bleeding weigh heavily in
      the balance of potential harm versus potential benefit of dabigatran, rivaroxaban
      and apixaban. When an oral anticoagulant is required, it is best to choose
      warfarin, a vitamin K antagonist, and the drug with which we have the most
      experience, except in those rare situations in which the INR cannot be maintained
      within the therapeutic range.

PMID- 23866360
TI  - "Antioxidants": no preventive effect against colorectal cancer.
AB  - "Antioxidants" do not reduce the incidence of polyps or colorectal cancer. Some
      antioxidants provoke serious adverse effects or even increase mortality.

PMID- 23866361
TI  - CT scans in childhood: leukaemia, brain tumours.
AB  - Radiation exposure from CT scans exposes children to an increased risk of
      leukaemia and brain tumours.

PMID- 23866362
TI  - Pharmacogenetics and personalised medicine: maintain a critical approach.
AB  - The purpose of pharmacogenetics is to offer"personalised" treatment, in which a
      drug is only prescribed to patients in whom it is very likely to be effective, or
      to withhold a drug from patients at increased risk of adverse effects.
      Pharmacogenetics requires the use of genetic tests which, as with any other
      diagnostic test, must be evaluated for their discriminatory power (sensitivity,
      specificity, etc.). These evaluations are sometimes biased. Pharmacogenetics has
      been heralded as a means of tailoring cancer therapy. However large clinical
      trials with demanding clinical endpoints are often disappointing, despite
      initially encouraging results. Pharmacogenetic information is included in many
      summaries of product characteristics for non-cancer drugs, mainly in order to
      reduce the frequency of certain serious adverse effects. In summary,
      pharmacogenetics theoretically represents a step forward but must be evaluated in
      rigorous clinical trials, as is the case with all other "therapeutic tools".

PMID- 23866363
TI  - Genetic testing: what are the objectives?

PMID- 23866364
TI  - Too many unreliable guidelines.

PMID- 23866365
TI  - Drug company influence starts at university.
AB  - Various studies have shown that medical students have frequent interactions with
      drug companies, which can influence their attitudes. Teachers and students in
      healthcare professions have a key role to play in defining and establishing
      relationships with industry that do not harm the quality of their training or
      practice.

PMID- 23866366
TI  - The finances of Association Mieux Prescrire: 2012 Prescrire annual report.

PMID- 23866367
TI  - Quo vadis hospice? Current and future directions in hospice.

PMID- 23866368
TI  - Why can't hospices participate in ACOs?

PMID- 23866369
TI  - Consider the conversation: how do we want it to end?

PMID- 23866370
TI  - Embracing discomfiting discourse.

PMID- 23866371
TI  - The pain of job change or loss.

PMID- 23866372
TI  - Conventions focus on child poverty.

PMID- 23866373
TI  - CPR in assisted living - revisiting a complex care issue.

PMID- 23866374
TI  - Retraction. Exendin-4 reverses biochemical and behavioural deficits in a pre
      motor rodent model of Parkinson's disease with combined noradrenergic and
      serotonergic lesions.

PMID- 23866375
TI  - Authors' reply. Why countries ban asbestos: the roots of political will.

PMID- 23866376
TI  - Authors' response to comments on Petty et al. (2011), "a quantitative method for
      estimating dermal benzene absorption from benzene containing hydrocarbon
      liquids," IJOEH, 17:287-300 by Pamela R.D. Williams, Jennifer Sahmel, Annette
      L.Bunge, Jeffrey Knutsen, and John Spencer.

PMID- 23866377
TI  - Response.

PMID- 23866378
TI  - Response.

PMID- 23866379
TI  - Refresher.

PMID- 23866380
TI  - Patient Protection and Affordable Care Act; Exchange functions: standards for
      Navigators and non-Navigator assistance personnel; consumer assistance tools and
      programs of an Exchange and certified application counselors. Final rule.
AB  - This final rule addresses various requirements applicable to Navigators and non
      Navigator assistance personnel in Federally-facilitated Exchanges, including
      State Partnership Exchanges, and to non-Navigator assistance personnel in State
      Exchanges that are funded through federal Exchange Establishment grants. It
      finalizes the requirement that Exchanges must have a certified application
      counselor program. It creates conflict-of-interest, training and certification,
      and meaningful access standards; clarifies that any licensing, certification, or
      other standards prescribed by a state or Exchange must not prevent application of
      the provisions of title I of the Affordable Care Act; adds entities with
      relationships to issuers of stop loss insurance to the list of entities that are
      ineligible to become Navigators; and clarifies that the same ineligibility
      criteria that apply to Navigators apply to certain non-Navigator assistance
      personnel. The final rule also directs that each Exchange designate organizations
      which will then certify their staff members and volunteers to be application
      counselors that assist consumers and facilitate enrollment in qualified health
      plans and insurance affordability programs, and provides standards for that
      designation.

PMID- 23866381
TI  - Final priority; National Institute on Disability and Rehabilitation Research-
      Rehabilitation Research and Training Centers. Final priority.
AB  - The Assistant Secretary for Special Education and Rehabilitative Services
      announces a priority for the Disability and Rehabilitation Research Projects and
      Centers Program administered by the National Institute on Disability and
      Rehabilitation Research (NIDRR). Specifically, we announce a priority for a
      Rehabilitation Research and Training Center (RRTC) on Community Living Policy.
      The Assistant Secretary may use this priority for competitions in fiscal year
      (FY) 2013 and later years. We take this action to focus research attention on
      areas of national need. We intend this priority to improve outcomes among
      individuals with disabilities.

PMID- 23866382
TI  - Statistics shed light on international education: foreign graduates constitute
      10% of U.S. workforce.

PMID- 23866383
TI  - Report finds benefits to foreign accreditation: task force still has questions
      about accreditation process.

PMID- 23866384
TI  - Generic cattle drug's sale halted after complaint: action follows lawsuit
      alleging likely "off-label" use.

PMID- 23866385
TI  - Unemployment and underemployment.

PMID- 23866386
TI  - Pill bottles with air to spare.

PMID- 23866387
TI  - Re: Patient with acute adrenal failure.

PMID- 23866388
TI  - Dr. Who? The next 'doctor' you see might be a nurse practitioner. Getting Health
      Care Right: one in a series.

PMID- 23866389
TI  - Author's response.

PMID- 23866391
TI  - 24th IAPD Congress in Seoul.

PMID- 23866390
TI  - Re: Posterior reversible encephalopathy syndrome.

PMID- 23866392
TI  - Sequencing-based tests to determine fetal down syndrome (trisomy 21) from
      maternal plasma DNA.

PMID- 23866393
TI  - Authors' reply.

PMID- 23866394
TI  - Dialysis in the Kingdom of Saudi Arabia.

PMID- 23866395
TI  - Beyond morphology: unraveling the genetic basis of childhood nephrotic syndrome
      in Pakistan.

PMID- 23866396
TI  - Association between tumour volume and recurrence of squamous cell carcinoma of
      the head and neck.
AB  - OBJECTIVE: To evaluate the prognostic significance of computerized tomography
      derived tumour volume for squamous cell cancers of the head and neck, treated
      primarily by surgery. METHODS: The retrospective review study comprised 72
      patients with head and neck malignancies who were treated primarily by surgery at
      Aga Khan University Hospital, Karachi, with/without adjuvant. It was done from
      May 2007 to November 2008. Each patient was followed up for a minimum of one year
      to check for recurrence. For statistical analysis SPSS 17 was used. Frequencies,
      cross-tabulations with chi square tests to find associations, binary logistic
      regression analysis, Cox regression analysis and receiver operating
      characteristic curve tests were run on the data. RESULTS: Overall, the median
      tumour volume for patients with recurrent disease was 52cm3 compared to 22cm3 for
      those who did not have a recurrence. It was found that large tumour volume was
      associated with a significantly higher chance of recurrence (p = 0.009).
      Laryngeal cancers with volumes greater than 46cm3 and oral cancers with volumes
      greater than 23.1cm3 were associated with poor prognosis. CONCLUSIONS: The
      primary tumour volume can represent an important prognostic factor for treatment
      outcome. Patients with larger primary tumour volumes should be treated more
      aggressively.

PMID- 23866397
TI  - Problems and prospects of acquistion of human cadaver for medical education in
      Nigeria.
AB  - OBJECTIVES: To determine the factors affecting cadaver acquisition in Nigeria,
      and to find a solution to the problem. METHODS: The research was conducted from
      May 2009 to November 2010 in the Anatomy and Histopathology Departments of
      selected medical schools and government hospitals in Nigeria. It was a
      retrospective study done on the basis of simple random sampling technique. A
      total of 38 questionnaires were distributed of which 34 were received and
      analysed statistically by percentage method. RESULT: Problems identified in
      cadaver acquisition included: religion, culture, ignorance and love even after
      death. Steps which may change the scenario were identified as education,
      provision of ambulance and donation centres, improved acquisitions procedures and
      formalities, and government legislation. Alternatives to cadaver dissection
      include the use of audio-visual aids, models of body parts and anirnal bodies,
      but the scarcity of cadavers in most colleges will affect the quality of
      anatomical knowledge and subsequent clinical practice. CONCLUSION: The supply of
      cadavers will remain scarce and affected by religious and moral factors. There is
      a need to promote the concept of voluntary donation of one's body for the good of
      the others which is essentially a humanitarian approach and rewarding in terms of
      promoting the cause of medical education in Nigeria.

PMID- 23866398
TI  - Criteria indicating morbidity in tuberculous meningitis.
AB  - OBJECTIVE: To work out a criterion that may indicate morbidity in tuberculous
      meningitis. METHODS: The retrospective study was conducted at the Medical Unit of
      the Liaquat University of Health Sciences, Jamshoro, Pakistan, and included cases
      related to a period between January 2006 and June 2011. Record of 50 patients
      were evaluated for clinical features, chest radiograph, Mantoux test, sputum for
      acid fast bacilli, routine investigations, cerebrospinal fluid studies,
      computerised tomography scan and magnetic resonance imaging of head. All the
      patients in the study had been treated with conventional approach. The severity
      of the condition was classified in stages, I, II and III. Clinical features,
      laboratory findings and imaging reports were analysed through SPSS 10 to find out
      the criteria indicating morbidity. Mean, median, standard deviation were
      calculated. Student t-test was applied on variables. RESULTS: Of the 50 patients,
      26 (52%) were male and 24 (48%) were female. Their ages ranged from 12 to 70
      years. Mean age was 37.72 +/-19.65 years. Median age was 35.54 years. Of the
      total, 17 (34%) patients recovered completely without any complications. Their
      mean age was 24+/-8.98 years and their mean time interval from onset of illness
      to presentation in the hospital was 21.75+/-9.75 days. Besides, 30 (60%) patients
      persisted with neurological sequelae, including cranial nerve palsies,
      hemiplegia, and hydrocephalus. Patients with neurological sequelae had mean age
      of 48+/-17.48 years and their mean time interval from onset of illness to
      presentation in the hospital was 41.33+/-14.14 days. Hydrocephalus was seen in 10
      (20%) patients. Three (6%) patients expired. Clinical features, laboratory
      findings and imaging reports analysis showed that the criteria indicating
      morbidity were increasing age of the patient (p=0.037), late diagnosis (p=0.044),
      advancing stage of disease, and development of hydrocephalus. CONCLUSION:
      Increasing age of the patient, late diagnosis, advancing stage of the disease and
      the development of hydrocephalus indicate morbidity in tuberculous meningitis.

PMID- 23866399
TI  - Macrolide and fluoroquinolone resistance in Helicobacter pylori isolates: an
      experience at a tertiary care centre in Pakistan.
AB  - OBJECTIVE: To assess fluoroquinolone and clarithromycin susceptibility pattern
      along with the types of genomic mutations involved in the resistance of
      Helicobacter pylori isolates. METHODS: The cross-sectional study was conducted at
      the Department of Pathology and Microbiology, Aga Khan University Hospital,
      Karachi, from June 2009 to July 2010, and comprised 162 gastric biopsy samples
      which were tested with GenoTypeHelicoDR (Hain Lifescience GmbH, Germany), a
      reverse hybridisation multiplex polymerase chain reaction (PCR) line probe assay
      (LiPA). Also, 23S rRNA (ribosomal ribonucleic acid) gene was analysed with three
      point mutations at A2146G, A2146C and A2147G for clarithromycin, and gyrA gene
      was analyzed at two codon positions 87 and 91 for fluoroquinolone susceptibility
      testing. SPSS 19 was used for statistical analyses. RESULTS: Clarithromycin
      resistance was seen in 60 (37.0%) of the isolates mainly involving mutation at
      A2147G (85%) followed by A2146G (n=35; 21.6%) and A2146C (n=19; 11.6%).
      Fluoroquinolone resistance was noted in 101(62.3%) isolates, while gyrA mutations
      at codon 87 was seen in 64 (39.6%) and at codon 91 in 66 (40.6%). Isolates
      showing combined resistance to both antibiotics were 44 (26.9%). CONCLUSION: High
      rate of resistance to fluoroquinolones was seen despite the fact that the drug
      was not part of the first-line anti-helicobacter therapy. There was moderate
      increase of clarithromycin resistance beyond the cutoff rates where empirical use
      of this antibiotic is abandoned. The findings warrant the need for pre-treatment
      susceptibility testing in Helicobacter pylori infections, especially in Pakistan
      where burden of disease is high and very limited data is available, to improve
      patient care by providing targeted therapy.

PMID- 23866400
TI  - A creeper, Coccinia indica, has anti-hyperglycaemic and anti-ureogenic effects in
      diabetic rats.
AB  - OBJECTIVE: To explore how ethanolic extract of Coccinia indica affects normal and
      diabetic rats. METHODS: The case-controlled animal study was conducted in June
      2008 at the Department of Biochemistry and Molecular Biology, University of
      Dhaka, Bangladesh. Two groups of 10 male rats each - one streptozotocin-induced
      diabetics and the other normal - were fed orally aqueous suspension of residue
      extracted from C. indica leaves with 60% ethanol after 18 hours of fasting. After
      90 minutes of oral administration, the rats were sacrificed, and blood level of
      glucose and free fatty acids and hepatic arginase activity were analysed.
      RESULTS: The blood sugar level had significantly decreased by 23% (p <0.01) and
      28% (p <0.001) in the normal and diabetic rats. Level of blood-free fatty acid
      was depressed by 15% (p <0.01) and 25% (p <0.001) in the two groups respectively.
      Moreover, the activity of hepatic arginase, a key urea cycle enzyme, was
      significantly depressed by 14% (p < 0.05) and 22% (p < 0.02) in the normal and
      diabetic groups. CONCLUSION: Results suggested that C. indica extract had anti
      hyperglycaemic and anti-ureogenic effects on the diabetic rats as judged by the
      decreased level of blood glucose and fatty acid and hepatic arginase activity.

PMID- 23866401
TI  - Comparison of need and supply of syringes for therapeutic injections in Pakistan.
AB  - OBJECTIVES: To determine the extent of shortfall in syringes by measuring the
      need from nationally validated sources and comparing it with position on the
      supply side. This was done in order to contribute to the ongoing national
      discussions that have focused on increasing syringe supply to curtail syringe
      reuse. METHODS: Using 'Injections received' data from the Pakistan Demographic
      Health Survey 2006-7 (N: 5429) and the National Hepatitis Survey (N: 47,043), the
      study estimated the number of injections received in Pakistan. We matched these
      against the local syringe production figures from the syringe manufacturers'
      association and import figures from the Federal Board of Revenue (FBR). RESULTS:
      Approximately 731+/-867 million injections (5.1 12 injections per head) are
      received annually in Pakistan and around 861+/-961 million syringes are supplied
      to the open market. Overall, 52-77% Pakistanis receive at least one injection in
      any given year. CONCLUSIONS: Injection need in Pakistan is among the highest
      worldwide but is completely matched by available syringe supplies, suggesting
      lower reuse than previously considered. However, highly prevalent Hepatitis B and
      C viruses suggest that even this reuse is a major public health concern and
      measures directed at both providers and recipients of injections are needed to
      curtail high injection need and syringe reuse.

PMID- 23866402
TI  - Helical CT scan with 2D and 3D reconstructions and virtual endoscopy versus
      conventional endoscopy in the assessment of airway disease in neonates, infants
      and children.
AB  - OBJECTIVES: To study the use of helical computed tomography 2-D and 3-D images,
      and virtual endoscopy in the evaluation of airway disease in neonates, infants
      and children and its value in lesion detection, characterisation and extension.
      METHODS: Conducted at Al-Noor Hospital, Makkah, Saudi Arabia, from January 1 to
      June 30, 2006, the study comprised of 40 patients with strider, having various
      causes of airway obstruction. They were examined by helical CT scan with 2-D and
      3-D reconstructions and virtual endoscopy. The level and characterisation of
      lesions were carried out and results were compared with actual endoscopic
      findings. Conventional endoscopy was chosen as the gold standard, and the
      evaluation of endoscopy was done in terms of sensitivity and specificity of the
      procedure. For statistical purposes, SPSS version 10 was used. RESULTS: All CT
      methods detected airway stenosis or obstruction. Accuracy was 98% (n=40) for
      virtual endoscopy, 96% (n=48) for 3-D external rendering, 90% (n=45) for
      multiplanar reconstructions and 86% (n=43) for axial images. Comparing the
      results of 3-D internal and external volume rendering images with conventional
      endoscopy for detection and grading of stenosis were closer than with 2-D minimum
      intensity multiplanar reconstruction and axial CT slices. Even high-grade
      stenosis could be evaluated with virtual endoscope through which conventional
      endoscope cannot be passed. A case of 4-year-old patient with tracheomalacia
      could not be diagnosed by helical CT scan and virtual bronchoscopy which was
      diagriosed on conventional endoscopy and needed CT scan in inspiration and
      expiration. CONCLUSION: Virtual endoscopy [VE] enabled better assessment of
      stenosis compared to the reading of 3-D external rendering, 2-D multiplanar
      reconstruction [MPR] or axial slices. It can replace conventional endoscopy in
      the assessment of airway disease without any additional risk.

PMID- 23866403
TI  - Comparison of SF-36 and WHOQOL-100 life quality scales in early period
      tuberculosis subjects.
AB  - OBJECTIVE: To determine the quality of life levels of early-period tuberculosis
      subjects by using the Short Form-36 and World Health Organisation's Quality of
      Life-100 scales and to compare the similar fields of the two scales. METHOD: The
      cross-sectional research, including 92 active tuberculosis subjects, was
      conducted from January 2007 to January 2008 at the Ministry of Health and
      Research's Sanitorium in Kayseri, Turkey. The two standard formats and a survey
      form developed by the authors were used as a means of data collection. The Bland
      Altman method was used to determine the adaptation of standard protocols in
      physical, social and psychological functions, general health perception, pain and
      vitality areas. SPSS version 15 was used for data analysis. RESULTS: As a result
      of applied correlation analysis, a positive significant, but moderate, common
      relation was found between the two scales as regards similar subfields (physical
      function r=0.391, general health perception r=0.436, social relations r=0.411,
      and spiritual health r=0.546) (p< 0.001). The subgroups of the scales Cronbach
      Alfa reliability coefficient were observed to vary between 0.63 to 0.94.The
      adaptability of the two scales was observed under physical, social and
      psychological functions, general health perception, pain and vitality/energy
      subfields by the Bland-Altman method. CONCLUSION: Our study revealed the fact
      that there was adaptability between similar subfields of the two standard
      protocols in early-period tuberculosis subjects.

PMID- 23866404
TI  - Bedtime and its correlates among secondary school children in Karachi, Pakistan.
AB  - OBJECTIVES: To determine the demographic and lifestyle predictors of bedtime
      among secondary school children in Karachi, Pakistan, and to assess what
      variables of daytime functioning correlate with bedtimes. METHODS: The cross
      sectional study was conducted between September and October 2007, among secondary
      school students aged 10-16 years, in the socio-economically diverse city of
      Karachi. Data was collected using a pre-tested self-reporting questionnaire, and
      analysed by univariate and multivariate logistic regression analysis on SPSS
      version 15. A p value of <0.05 was considered significant. All odds ratio were
      recorded with a 95% confidence interval. RESULTS: Of the 539 students in the
      study, 102 (18.92%) were male and 437 (81.07%) were female. Of the total, 401
      (74.4%) slept late (after 10pm). Homework and TV shows were more frequent reasons
      of bedtime among the late-sleepers, whereas parental influence was reported more
      by the early-sleepers. Advancing grade at school, father's profession as doctor
      or engineer and sleeping alone in the room were independent predictors of late
      bedtime on multivariate analysis (p<0.05). Students who were older, did not share
      a bed, or slept for >3 hours during the afternoon, were more likely to sleep
      after 10pm on univariate analysis only (p<0.05). Students sleeping late were more
      likely to get less daily and nocturnal sleep, wake-up later, require multiple
      wake up reminders in the morning, fall asleep in a morning class and feel tired
      during the day (p<0.05). They were also 2.42 times less likely to feel that they
      got adequate sleep to be fresh in the morning (p<0.001; 95% CI 1.58-3.72).
      CONCLUSION: More than three-fourth of our secondary school children sleep late.
      Parents and teachers should foster healthy sleeping habits and early bedtimes
      among students to allow optimal daytime functioning.

PMID- 23866405
TI  - A comparison of the effects of desflurane and isoflurane on rat pulmonary
      parenchyme histopathology and malondialdehyde levels.
AB  - OBJECTIVE: To evaluate the lipid peroxidation and pulmonary histopathology after
      desflurane and isoflurane anaesthesia in rats. METHODS: The study was conducted
      in the faculty of Veterinary.Medicine Animal Laboratories, Ankara University,
      between January and December 2009. Twenty-four Wistar-Albino rats were studied
      and classified randomly into three equal groups. The control group (n=8) was made
      to inhale 50% O2 for 60 minutes; the isoflurane group (n=8) received 50% O2+1.2%
      isoflurane for 60 minutes; and the desflurane group (n=8) was given 50% O2+6%
      desflurane, again for 60 minutes. As the sham group, one rat was sacrificed via
      intracardiac blood aspiration. Rat pulmonary tissue parenchyma samples were
      evaluated for peribronchial inflammatory infiltration, alveolar septal
      infiltration, alveolar oedema, exudation, alveolar histiocyte and tissue
      malondialdehyde levels. RESULTS: When compared with the control group,
      peribronchial inflammatory infiltration levels were found to be considerably high
      in the desflurane and isoflurane groups (p= 0.0031). In addition, the alveolar
      hystiocytes were much higher in the desflurane group than in the control group
      (p<0.05). Tissue malondialdehyde levels were found to be significantly higher in
      both groups than in the control group. CONCLUSION: Desflurane significantly
      increased pulmonary inflammation more than isoflurane in rat pulmonary parenchyma
      that indicates an inflammatory response. Besides, it was determined that the
      significantly higher malondialdehyde levels in both the desflurane and the
      isoflurane groups resulted in an increase in the membrane lipid peroxidation via
      volatile anaesthetics.

PMID- 23866406
TI  - Relationship between visfatin and some clinical and biochemical parametres in
      peritoneal dialysis patients.
AB  - OBJECTIVE: To characterise the relationship between visfatin levels and various
      clinical and biochemical parameters in peritoneal dialysis patients. METHODS: The
      case-control study was conducted at the Medical Faculty Hospital, Yuzuncu Yil
      University, Van, Turkey, between May 2007 and December 2008, and involving 41
      patients on peritoneal dialysis, 20 haemodialysis patients and 20 healthy
      controls. Fasting visfatin level was measured with enzyme-linked immunosorpent
      assay (ELISA) method, and patients on peritoneal dialysis were separated into two
      groups according to the visfatin levels - high and low. The groups were compared
      in terms of some clinical (height, weight, body mass index, waist circumference,
      hip circumference, waist/hip ratio, heart rate, systolic and diastolic blood
      pressure and the kt/V and CrCI (creatanine clearance) parameters which are
      indicative of the dialysis adequacy) and biochemical parameters (glucose,
      triglycerides, cholesterol, low density lipoprotein, high density lipoprotein,
      aspartate aminotransferase, alanine transminase, blood urea nitrogen, creatinine,
      total protein, albumin, globulin, sodium, potassium, magnesium, calcium,
      phosphorus, ferritin, venous blood gas, parathyroid hormone and insulin). SPSS 15
      was used for statistcal analysis. RESULTS: No statistically significant
      difference in the visfatin levels was found between the patients and controls
      (7.71 +/- 4.04, 7.36 +/- 3.71, 7.70 +/- 1.61, respectively, p = 0.63). The
      triglyceride level of the high-visfatin group was significantly higher than that
      of the low-visfatin group (243.8 +/- 133.2, 150.8 +/- 65.8, respectively,
      p<0.05). However, there was no correlation between visfatin and triglyceride
      levels. No difference in the other clinical and biochemical parametres was
      observed between the two groups of peritoneal dialysis patients. CONCLUSIONS: No
      significant difference in the serum visfatin levels of peritoneal dialysis
      patients compared to haemodialysis patients or healthy individuals was noticed.
      Further studies are needed to confirm the effect of visfatin on triglyceride
      levels, and, if confirmed, the mechanism of this relation.

PMID- 23866407
TI  - Students' perception about logbooks: advantages, limitation and recommendation -
      a qualitative study.
AB  - OBJECTIVE: To identify students' perception concerning advantages, limitations
      and recommendations about logbooks. METHODS: In this qualitative-phenomenology
      study, conducted from January to December 2010, 14 undergraduate nursing students
      were selected by random sampling. The study was done in the neonatal intensive
      care unit and paediatrics ward of a regional hospital in Bojnord, Iran. At the
      beginning of the courses, the tutor explained the specific objectives of the core
      curriculum and how to complete the logbooks. During the course, formative
      assessment and related feedback were noted down. At the end, two semi-structured
      focus groups were generated. All interviews were recorded, transcribed and
      analysed for emerging themes and concepts. RESULTS: Based on content analysis,
      three advantages and four limitations of logbooks were identified and
      recommendations were noted. CONCLUSIONS: An appropriate logbook should be
      inexpensive, feasible and acceptable to students and should allow rapid
      collection of valid, relevant and reliable data. However, its methodology needs
      to be revised.

PMID- 23866408
TI  - The effect of simvastatin on picrotoxin-induced seizure in mice.
AB  - OBJECTIVE: To study the effect of simvastatin on picrotoxin-induce seizures in
      mice in order to understand the impact of gabaergic system on neuronal cell
      death. METHODS: The study was held between July and September 2011, at the
      Karadeniz Technical University in Trabzon, Turkey. Balb/c mice weighting 20-40g
      were randomly selected and divided into five groups of six each. The first group
      was designated as control group; and the second as the picrotoxin (10mg/kg;
      intraperitoneal) alone group. The rest of the groups were administered
      simvastatin in dozes of 10, 20 and 40mg/kg respectively. Onset, number and
      duration of seizures, and death time were measured in mice for one hour. At the
      end of the study, the brain was removed from mice and normal and degenerative
      pyramidal neurons were counted in hippocampal CA1, CA2, CA3 region by light
      microscope. Using SPSS 17, Mann=Whitney U and Chi square and student-T tests were
      performed for statistical analysis. RESULTS: Simvastatin (10mg/kg) significantly
      decreased the number and duration of picrotoxin-induced seizures in mice. In
      addition, Simvastatin (10, 20, and 40mg/kg) significantly reduced the total
      number of abnormal pyramidal cells in CA1 and CA3 hippocampal regions compared to
      the picrotoxin-alone group. CONCLUSION: The effect of simvastatin on picrotoxin
      induced seizures may be the result of increase in gabaergic activity and decrease
      in glutamatergic activity. More studies are needed to validate these results.

PMID- 23866409
TI  - An evaluation of the sling surgical method of the bulbar urethra in the treatment
      of men's stress urinary incontinence at Shohadaye Ashayer Teaching Hospital in
      2008.
AB  - OBJECTIVE: To evaluate the utility and efficacy of bulbar urethera sling in the
      management of sphincter insufficiency that usually occurs after prostate surgery
      or posterior urethral injuries and may lead to moderate to severe stress
      incontinence. METHODS: A total of 30 patients underwent sling surgery with rectus
      fascia in a four-year period at the Shohadaye Ashayer Teaching Hospital in Iran.
      Urinary incontinence occurred in 8 patients after open prostatectomy, in 12
      patients after prostatectomy through urethra, in 8 patients after radical
      prostatectomy. For the purpose of the study, 2 patients in whom incontinence
      occurred after pelvic fracture were excluded. The 28 patients were followed up
      for a one-year period after the operation. All patients had incontinence from one
      to six years. After hospitalisation, an 18 gauge Foley's catheter was introduced
      in the urethra in every patient. The perineum was incised longitudinally, and the
      bulbar urethra was freed and a 2x7 cm span of rectus fascia was separated and
      placed under the bulbar urethra. Treatment was defined as use of one or no pad
      per day and recovery, as a reduction of at least 50% in the number of the used
      pads after sling operation. RESULTS: After operation, all patients suffering from
      moderate to severe stress incontinence were treated with 0-1 pad per day. Four
      patients were unable to urinate; in 2 patients the sling was modified and
      loosened, and in two others dilatation resolved their problems. CONCLUSION:
      Bulbar urethra sling can be carried out in moderate to severe urinary
      incontinence treatment in any hospital at a modest cost with satisfactory
      results.

PMID- 23866410
TI  - Evaluation of the efficacy of once-daily use of tadalafil vs. on-demand use. Is
      there a cumulative effect?
AB  - OBJECTIVE: To assess and compare the efficacy of on-demand versus daily dosages
      of tadalafil in the treatment of erectile dysfunction. METHODS: The case-control
      double-blind study was conducted at the Department of Urology, Tehran University
      of Medical Science, Imam Khomeini Hospital, from March 2008 to January 2010. It
      comprised 100 males suffering from erectile dysfunction who were randomised into
      two groups; one receiving on-demand tadalafil (10mg), and the other receiving
      once-daily dose of tadalafil (10mg). The erectile function domain of the
      International Index of Erectile Function was evaluated initially at the baseline
      and then at 24 weeks after treatment. To evaluate the possible cumulative effect
      of tadalafil, the index was measured in the group taking daily tadalafil at 12
      weeks after the initiation of the treatment. SPSS 13 was used for statistical
      analysis. RESULTS: The study showed significant improvement in the mean erectile
      function domain measured after 24 weeks in both daily (17.08+/-3.896 vs baseline
      12.64+/-2.92; p<0.001) and on-demand (15.46+/-3.64 vs baseline 13.48+/-2.86;
      p<0.001) groups. Data showed significant difference in mean scores between on
      demand and daily groups (p = 0.03). In daily group, the mean domain measured at
      the 24th week showed significant improvement compared to the mean score of the
      12th week (p <0.001). CONCLUSION: Treatment with daily tadalafil was associated
      with a significantly higher erectile function domain score compared to the on
      demand use. The significant difference between mean scores of 12th week and 24th
      week in the daily group points towards the possible cumulative effect of
      tadalafil.

PMID- 23866411
TI  - Perceptions and myths regarding oral health care amongst strata of low socio
      economic community in Karachi, Pakistan.
AB  - OBJECTIVES: To determine the prevalence of dental myths and perceived knowledge
      regarding oral healthcare practices and its associations with levels of education
      amongst low socioeconomic strata in Karachi, Pakistan. METHODS: The cross
      sectional study was conducted in January 2011. Two-staged random sampling was
      conducted to achieve a sample size of 576 participants from 8 union councils of
      Gadap Town, Karachi, Pakistan. An interview-based questionnaire was used to
      determine the participants' perceptions towards oral health and hygiene practices
      as well as the prevalence of common dental myths. The subjects were interviewed
      through a formulated questionnaire that was cross-translated into Urdu language.
      RESULTS: Response rate from the participants was 550 (95.48%). Of the total, 270
      (47%) respondents believed in the myth of tooth extraction affecting the eye
      vision. This was significantly associated with the socio-demography of the
      respondents. Besides, 421 (73%) thought that tooth extraction is not the ultimate
      remedy for pain relief and it was statistically significant with age and
      educational status of the participants. Those who considered bleeding while
      brushing to be normal were 144 (25%), and it was significantly associated with
      age and education level. Impact of oral health on general health was positively
      responded by 392 (68%), while 418 (72.5%) respondents did not think that the
      retention of baby teeth is important. Both these perceptions were significantly
      associated with age and level of education. CONCLUSION: Pakistani population has
      considerable belief in myths and false perceptions regarding oral health issues.
      Various stakeholders should be involved to develop policies towards healthy
      attitudes and beliefs within the community towards their oral healthcare.

PMID- 23866412
TI  - Twin births and their complications in women of low socioeconomic profile.
AB  - OBJECTIVE: To determine the frequency of twin births and their foetomaternal
      complications in women of low socioeconomic profile. METHODS: The cross-sectional
      study was conducted from January 2009 to December 2010 at the Obstetrics and
      Gynaecolgy Unit I, Civil Hospital, Karachi. Patients with twin pregnancy giving
      birth beyond 24 weeks, were selected by non-probability purposive sampling. Data
      on patient characteristics, gestation, antepartum and peripartum complications,
      chorionicity, mode of delivery and perinatal outcome was recorded and analysed
      through SPSS 16. RESULTS: Out of 6077 deliveries during the study period, 119
      twin births gave a frequency of 19.58/1000 births. Patients' mean age was 27.51+/
      4.2 years, mean parity 2.4+/-2.2 and mean gestational age was 34.76+/-3.4 weeks.
      Unbooked and referred patients were 96 (80.67%). Final paired outcome was alive
      twin pairs in 74 (62.18%) cases, stillbirth in 7 (5.88%), neonatal deaths in 10
      (8.40%). Perinatal mortality rate was 277/1000 twin births. Most frequent foetal
      complications were low birth weight (n=84; 70.58%), pre-term births (n=70;
      58.82%) and intrauterine growth restriction (n=59; 49.57%). The second twin was
      at significantly higher risk (p< 0.05). Monochorionic twins had significantly
      high rates of stillbirths than dichorionic (p = 0.023). Most frequent maternal
      complications comprised pre-term labour (n=56; 47.05%), severe anaemia (n=22;
      18.48%), hypertensive disorders (n=19; 15.96%) and postpartum haemorrhage (n=10;
      8.40%). CONCLUSION: Twin pregnancies in women of low socioeconomic profile result
      in very high rates of low birthweight, pre-term births, intrauterine growth
      restriction, anaemia, hypertensive disorders and postpartum haemorrhage.
      Monochorionic pregnancies result in high rates of stillbirths and second twin is
      more likely to be compromised.

PMID- 23866413
TI  - Factors associated with stress among adolescents in the city of Nawabshah,
      Pakistan.
AB  - OBJECTIVE: To identify the risk factors of stress among school-going adolescents
      in rural Nawabshah, Pakistan. METHODS: The cross-sectional study was conducted in
      2005, comprising 800 school-going children of 10-16 years of age in Nawabshah,
      through simple random sampling. Data was collected using a structured
      questionnaire to assess the potential risk factors of stress. A modified version
      of Perceived stress scale was utilized to measure stress level. SPSS 12 was used
      for statistical analysis, while multiple linear regression analysis was run to
      identify the factors associated with stress in the study population. RESULTS: Of
      the total, 529 (66%) children belonged to state-run schools while 271 (34%) were
      studying at private facilities. The mean age was 13.7+/-1.3 years. The level of
      stress was positively associated with the number of siblings, parental conflicts,
      the age of the mother and the number of rooms in the household. There was
      decreased level of stress among female adolescents (n=474; 59.3%) who had prior
      information about pubertal body changes than the boys (n=326; 40.8%). CONCLUSION:
      The study showed that stress among adolescents can be reduced by modifying socio
      economic and demographic factors.

PMID- 23866415
TI  - Using the potentials of community pharmacies to promote rational drug use in
      Pakistan: an opportunity exists or lost?
AB  - Keeping in view the importance of community pharmacies and their outreach to the
      patients, many developing countries have used their potential to promote safe and
      effective treatments by building their dispensing practices. This article
      discusses the importance of community pharmacies in the context of healthcare
      delivery system, and the potentials and opportunities which exist to promote the
      rational use of medicine in developing countries, especially Pakistan. A
      systematic inventory of published research work, was conducted for which the
      general search engine Google was utilised by using key terms 'community
      pharmacies,' 'dispensing practices,' 'drug sellers,' 'developing countries,'
      'pharmacist,' 'Pakistan,' 'quality of pharmacies' and 'rational drug use' were
      employed. Internet databases, like Science Direct, Medline/Pub Med using
      available access, were used to find full-length articles. Private drug outlets
      have virtually turned into first-line source of prescribing and dispensing
      medications without any restrictions by the drug sellers. Innovative approaches
      are needed to achieve better services from these community pharmacies without
      significantly increasing costs to the society and healthcare system. The
      opportunity exists, but needs to be utlised accordingly.

PMID- 23866414
TI  - Comparison of Schirmer's test and tear film breakup time test to detect tear film
      abnormalities in patients with pterygium.
AB  - OBJECTIVE: To compare tear film breakup time test with Schirmer's test in
      patients with pterygium. METHODS: The case-control study, involving 86 patients
      with unilateral primary pterygium aged between 30 and 70 years, was conducted at
      the Department of Ophthalmology, Karachi Medical and Dental College, Abbasi
      Shaheed Hospital, from May 2009 to December 2010. The eye with pterygium was
      taken as the case, and was compared with the other eye without pterygium which
      was taken as the control in these patients. All patients underwent routine
      ophthalmic examination. Tear film tests such as Schirmer's test and tear film
      breakup time test were performed on all these eyes. Results of tear function test
      between the eyes with pterygium (cases) and the eye without pterygium (control)
      were compared. SPSS 17 was used for statistical analysis. Chi square test was
      used for comparing the results of the cases and the controls. RESULTS: Of the 86
      patients, 63 (73.3%) were men, while 23 (26.7%) were women. The median age was 41
      years. There were 62 (72.1%) patients with pterygium in the right eye, while 24
      (27.9%) had it in the left. Among the involved eyes, decreased tear breakup time
      (<10 seconds) was observed in 65 (75.6%) eyes, while 21 (24.4%) eyes did not show
      decreased tear breakup time i.e.>10 seconds. On the other hand, 8 (9.3 %) eyes
      with pterygium had Schirmer's test positive and 78 (90.7 %) eyes had it negative.
      CONCLUSION: Tear film breakup time test has better diagnostic value compared to
      Schirmer's test in detecting tear film abnormality in patients with pterygium.

PMID- 23866416
TI  - Misdiagnosed vitamin B12 deficiency a challenge to be confronted by use of modern
      screening markers.
AB  - Vitamin B12 deficiency is one of the common conditions in the elderly population
      leading to confusion, depression, memory loss and balance problems. Unfortunately
      there is no gold standard test for the diagnosis of cobalamin deficiency and a
      wide range of variation in reference levels according to country, and laboratory
      assay used. This poses a problem in diagnosing this condition making it a
      commonly misdiagnosed medical entity. There is current emphasis on need for
      clearer guidelines and much research is still being done to pave ways to
      determine better reference values for serum B12 and other screening tests. It is
      advised that screening methods are used adjunctively for the purpose of screening
      individuals.

PMID- 23866417
TI  - Weight loss with interferon and ribavirin therapy in chronic hepatitis C
      patients.
AB  - Recommended treatment of chronic Hepatitis C virus (HCV) infection is interferon
      and ribavirin. Most patients develop side effects during treatment. Weight loss
      is one of the side effects of interferon therapy. Present study was conducted at
      Pakistan Medical and Research Centre (PMRC), Jinnah Postgraduate Medical Centre
      (JPMC), Karachi from January 1998 - December 2010, to find out the frequency,
      extent of weight loss, its recovery after interferon therapy and the impact of
      weight loss on treatment response. Body weight was recorded on regular outpatient
      visits i.e initially, then at 1, 3 and 6 months of treatment and six months post
      treatment. Out of 260 patients, 176 (67.7%) observed statistically significant
      weight loss (p<0.05), on completion of therapy as compared to initial visit.
      Weight loss during interferon therapy was found to be independent of age, gender,
      treatment outcome, serum albumin, haemoglobin, white blood cell (WBC) and
      platelet count. Body weight returned to baseline within six months after
      completion of treatment in most cases.

PMID- 23866418
TI  - Microlayertomography system.
AB  - In common radiography, the images of all bodys' structures lying within the path
      of radiation overlap each other. Tomography separates the required image from the
      surrounding area. Preliminary mechanism of sectional radiography, called the
      longitudinal tomography, does enhance the quality of image, but because of the
      different velocity of unwanted images, lying nearer to or further from axis
      central point, tomographic blurring does occur. Microlayer tomography with high X
      ray rotating velocity without tube movement provides images with depth perception
      of millimeter fraction, and there is no need for digital image reconstruction.
      The pace of the procedure is exceptional. Hence, the tomographic slices can be
      prepared in about less than 0.02 second. Besides, the cost of patient treatment
      as well as system maintenance is much less compared to those computed tomography
      (CT) and magnetic resonance (MRI) scans. This article will discuss the technology
      in the context of a phantom trial that was conducted at the Shahid Beheshti
      Medical University, Iran. The trial of the system prototype led to results that
      reflexted well on the procedure.

PMID- 23866419
TI  - An unusually prolonged duration of spinal anaesthesia following 0.5%
      levobupivacaine.
AB  - Spinal anaesthesia is the method of choice for elective caesarean delivery.
      Levobupivacaine may produce a sensory and motor block that is different from that
      produced by bupivacaine, the most popular local anaesthetic for parturients
      undergoing caesarean section (CS). We present a case of unexpectedly prolonged
      spinal anaesthesia following a successful spinal block with levobupivacaine.
      There was no evidence of any neurological injury in this patient during
      injection.

PMID- 23866420
TI  - Intra-mandibular canalicular adenoma: report of a rare case.
AB  - Canalicular adenomas are uncommon benign salivary gland neoplasms of the oral
      cavity. They are typically located on the upper lip, buccal mucosa and
      infrequently found on the palate and derived from minor salivary glands. Intra
      mandibular localization of canalicular adenoma is extremely rare. Due to benign
      character of the tumour, canalicular adenomas rarely present with bone erosion.
      Histologically, trabecular type of basal cell adenoma, pleomorphic adenoma and
      polymorphous low-grade adenocarcinoma should be discriminated from canalicular
      adenomas. A-56- year old female patient with asymptomatic intra-mandibular
      canalicular adenoma was presented. The lesion was managed surgically under local
      anesthesia and 2 year's follow up was uneventful. Only two other intra-mandibular
      canalicular adenoma cases have been reported up till now. This case report
      describes the third intra-mandibular canalicular adenoma, and reviews the
      literature.

PMID- 23866421
TI  - Regression of severe Behcet's eye disease with infliximab therapy; .first two
      cases treated in Pakistan.
AB  - We present two cases of Behcet's Disease with severe eye problems along with oral
      and genital ulcerations. Both cases, initially were treated with steroids and
      oral immunosuppressive agents, but did not show a response and ocular disease
      became worse. Both the cases were kept on Infliximab therapy. an immediate
      positive response with improvement in vision and symptoms was seen. After initial
      infusions the ocular damage in both the cases stopped.

PMID- 23866422
TI  - A novel mutation in MCPH1 gene in an Iranian family with primary microcephaly.
AB  - Primary microcephaly (MCPH) is a genetic disorder in which affected individuals
      present with a head circumference 3 standard deviations (SDs) below the age- and
      sex-related mean and is accompanied by mental retardation without further
      associated malformations. Here we report a patient with sporadic MCPH from
      Northwest of Iran who was investigated for MCPH1 locus. Clinical examination and
      karyotype analyses were performed and microsatellite based mapping was done by
      using flanking and intragenic short tandem repeat (STR) markers for MCPH1 locus.
      For these markers the affected individual was homozygote and the parents were
      heterozygote. According to this pattern of allele sharing and also the
      cytogenetic findings, mutation screening of Microcephalin gene was performed and
      subsequent sequencing revealed a novel mutation in Microcephalin gene.

PMID- 23866423
TI  - Imaging and intervention for coronary artery disease following irradiation of
      malignant thymoma.
AB  - Thymomas are rare malignant epithelial growths, constituting 20% of mediastinal
      tumours. Resection followed by irradiation may be employed in all thymomas except
      for stage 1 thymomas. Mediastinal irradiation is associated with coronary artery
      disease. The mean duration of presentation of post-irradiation coronary artery
      disease is 16 years (range 3-29 years). In our patient coronary artery disease
      was found only a year post irradiation. A 55 year old male who presented with
      complaints of dyspnoea, retrosternal chest pain and heaviness since one year
      underwent resection for malignant thymoma followed by radiotherapy. He presented
      with coronary artery disease a year after undergoing mediastinal irradiation. On
      follow-up, patient was treated successfully by coronary artery bypass graft. This
      case is an unusual occurrence and suggests that mediastinal irradiation may
      result in significant coronary artery disease as early as within one year.

PMID- 23866424
TI  - The use of physical restraints in mental health.

PMID- 23866425
TI  - Sarpogrelate- another new antiplatelet agent?

PMID- 23866426
TI  - Presenting your results-II: Inferential statistics.
AB  - The results are the most significant part of the article since they represent the
      original work of the authors. It is essential to apply the correct statistical
      tests. Data should be presented in a comprehensive but simple manner that is
      easily understandable by the general readership. Care should be taken to keep the
      tables and graphs simple and uncluttered. Also avoid duplication of the
      information in the text and tables/graphs. The most important thing to keep in
      consideration is that it is more relevant to present the main findings rather
      than all the findings of the study.

PMID- 23866427
TI  - The three musketeers: cellulitis, phlegmon and abscess.

PMID- 23866428
TI  - Knowledge attitude and practices among urban women of Karachi, Pakistan,
      regarding breast cancer.
AB  - OBJECTIVE: To determine the knowledge,attitudes and practices of urban women
      regarding breast cancer and its available screening modalities. METHODS: The
      cross-sectional, questionnaire-based, descriptive study was conducted in the
      urban population of Karachi in November 2010. Female attendants (n=373) visiting
      a tertiary care centre and four of its urban outreach centres during the study
      period were administered a questionnaire. The answers were then scored with
      regard to their knowledge. Frequencies and percentages were computed through SPSS
      17, and analysis of variance was used to confirm significance. RESULTS: Of the
      373 participants with a mean age of 32.4+/-10.9 years, 293 (78.6%) were married,
      and 257 (69%) were housewives. The education level was considerably high; with
      214 (57.4%) graduates. The mean score for knowledge of risk factors was 2.84 out
      of a total of 13; which was significantly associated with marital status and
      income. Age > 40 years, education level, income and employment status were also
      significantly associated with higher mean screening awareness scores. Nearly 182
      (48.8%) had heard about Breast Self Examination and 142 (38%) knew how to perform
      one. However, only 97 (25.9%) regularly performed such an exam. Almost all 3621
      (97%) women wanted more media awareness campaigns regarding the issue.
      CONCLUSION: There is a real need for comprehensive health education programmes
      focusing on breast cancer awareness in Pakistan.

PMID- 23866430
TI  - Telemedicine: distance matters not now.

PMID- 23866429
TI  - A clinical epidemiologic study of thyroid carcinoma in patients under 25 years
      old in Tabriz, Iran (1995-2010).
AB  - OBJECTIVE: To evaluate the epidemiology and prognostic factors of thyroid cancer
      among children and adolescents in Tabriz, Iran. METHODS: The retrospective
      descriptive-analytical study, assessing the tumour and characteristics of 356
      patients with thyroid carcinoma aged 5-25, was conducted at the Department of
      Surgery, Imam Khomeini Hospital, Tabriz University of Medical Sciences from April
      1995 to April 2010. All malignant neoplasms of the thyroid gland registered
      during the study period were studied, and their demographic and medical data was
      evaluated and, compared to identify the epidemiology and prognosis factors
      related to survival. SPSS 16 was used for statistical analysis. RESULTS: Of the
      total, there were 100 (28%) male and 256 (72%) female subjects, with their mean
      age being 12.6+/-8.4 years. In terms of the disease, there was no statistically
      significant difference between the two genders (p=0.65). The five-year survival
      rate was 345 (97%) in patients aged 5-25 years. Gender was not a statistically
      significant marker (p=0.82). CONCLUSION: The study indicated an increase in cases
      of thyroid cancer incidence. It also underlined the need for standardisation of
      diagnostic, classification and registration criteria which shall be a fundamental
      requirement for future studies of thyroid carcinoma in young people.

PMID- 23866431
TI  - Brutal chevron to keyhole laparoscopic radical nephrectomy--time to transform!

PMID- 23866433
TI  - Ureterovaginal fistula--etiological factors and outcome.
AB  - OBJECTIVE: To assess the etiological factors and the outcome of ureterovaginal
      fistula in an urban setting. METHODS: The observational study was conducted at
      the Armed Forces Institute of Urology, Military Hospital, Rawalpindi, from
      January 2009 to January 2011. All the patients of uretero-vaginal fistula at the
      centre were included on the basis of non-probability purposive sampling. The
      etiology, clinical presentation and the investigative procedures were recorded.
      The operative modality contemplated was noted and post-operative results were
      evaluated. The data was entered in a structured proforma and analysed for
      descriptive statistics using SPSS version 14.0. RESULTS: Seventeen cases of
      ureterovaginal fistula were recorded. Amongst these 10 (58.8%) were post
      hysterectomy, while 7 (41.1%) cases post-caesarean section. The emergency
      procedures performed by the residents/junior registrars contributed 12 (70.2%) of
      the cases. All these patients were treated surgically; 14 (82.3%) were managed
      with ureteroneocystostomy, 2 (11.7%) required Boari Flap reconstruction, and in
      psoas hitch was performed in 1 (5.8%) case. The time of intervention was 4 - 12
      weeks (9.76 +/- 2.223). Post-operatively, only 1 (5.8%) case had superficial
      wound infection and 1 (5.8%) urinary tract infection. All the patients remained
      dry with a follow-up period of 3 - 24 months (mean 12.24 +/- 6.879). CONCLUSION:
      Ureterovaginal fistula is one of the complications of emergency procedures,
      especially in the hands of inexperienced surgeons. Prompt diagnosis and surgical
      intervention produce excellent results. Intervention can be done safely as early
      as 4 weeks after the initiation of the condition.

PMID- 23866432
TI  - Species identification of invasive yeasts including Candida in Pakistan:
      limitations of phenotypic methods.
AB  - OBJECTIVE: To compare phenotypic and genotypic methods of yeast identification.
      METHODS: The in-vitro cross-sectional study was conducted from January 2006 to
      May 2009. Invasive yeasts isolated at the clinical microbiology laboratory at the
      Aga Khan University (AKU), Karachi, Pakistan, were identified. Speciation by
      phenotypic and molecular methods was compared. All yeasts isolated during the
      study period from blood and other invasive sites were identified using standard
      methods. Isolates were shipped to Mycotic Diseases Branch, Centres for Disease
      Control and Prevention, Atlanta, Georgia, USA, for identification by Luminex flow
      cytometric multianalyte profiling (xMAP) system. Ribosomal ITS2 DNA sequencing
      was performed on isolates not identified by Luminex. RESULT: Of the 214 invasive
      yeasts evaluated, Candida species were 209 (97.7%) while the frequency of non
      Candida species was 5 (2.3%). Overall agreement between phenotypic and molecular
      identification was 81.3%, 90.3% amongst the more common Candida species, and only
      38.8% amongst the uncommon yeasts. CONCLUSION: Phenotypic methods of
      identification proved adequate for common Candida species, but were deficient in
      recognising rare Candida and non-Candida yeasts, highlighting the importance of
      molecular methods for identification.

PMID- 23866434
TI  - Quality of life in patients on methadone maintenance treatment: a three-month
      assessment.
AB  - OBJECTIVE: To examine the 3-month effect of methadone maintenance treatment (MMT)
      on quality of life (QOL) of substance-dependent outpatients in Iran. METHODS: The
      qausi-experimental study performed at the Oral Maintenance Methadone Treatment
      Clinic of the Baharan Psychiatric Hospital, a university hospital in Zahedan,
      southeast of Iran, from 2009 to 2010. One hundred patients with substance
      dependence disorder were recruited from the outpatient clinic. Quality of life
      parametres were measured through the World Health Organization Quality of Life
      scale (WHO QOL-BREF) prior to the treatment, and 1, 2 and 3 months after starting
      the treatment in order to assess changes in the Quality of Life across the
      treatment period. Repeated measurement analysis was used for data analysis.
      RESULTS: Of the 100 subjects initially recruited, 83 (83%) completed the study
      period. The total Quality of Life score improved from pre-treatment to the first
      month into treatment. The improvement was maintained at the 2-month and 3-month
      points (P < .05). According to the World Health Organization subscales, the
      treatment was effective in improving physical and social relationship domains
      over time (P < .05), but there were no significant improvements in psychological
      and environmental domains. CONCLUSIONS: Oral methadone maintenance treatment was
      effective in improving the overall Quality of Life during the first three months
      of treatment in substance-dependent outpatients.

PMID- 23866435
TI  - Validity of aspartate aminotransferase to platelet ratio index as predictor of
      early viral response in patients with hepatitis C treated by interferon-based
      therapy.
AB  - OBJECTIVE: To observe any change in value of aspartate aminotransferase to
      platelet ratio index from the baseline and to compare it with the Hepatitis C
      virus ribonucleic acid at 12 weeks after the start of interferon-based treatment
      in patients with Hepatitis C. METHODS: The prospective study, conducted at the
      Department of Medicine, Liaquat University of Medical and Health Sciences
      Hospital, Jamshoro, Pakistan, from September 2009 to March 2010, included 158
      consecutive, chronic patients of Hepatitis C with grade > or = 2 fibrosis on
      liver biopsy, or having aspartate aminotransferase/Platelet ratio index of > 1.
      The aspartate aminotransferase to platelet ratio index was determined as
      aspartate aminotransferase level (upper normal limit)/platelets counts (10(9)/L)
      x 100. Eligible patients were assigned to receive thrice weekly subcutaneous
      injection of 3MIU standard interferon > or = -2b and weight-base dosage of
      ribavirin. The early virological response was defined as undetectable Hepatitis C
      virus ribonucleic acid test at week 12 of the study. APRI < 1 was considered to
      be the response to therapy. Paired sample t-test was applied to observe pre-and
      post-treatment mean +/- SD of continuous variables, while Chi-square test was
      applied for comparing categorical variables. A p-value of 0.05 was considered
      statistically significant. RESULTS: Out of 158 patients enrolled, 90 fulfilled
      the inclusion criteria. The aspartate aminotransferase to platelet ratio index
      before treatment was 1.61 +/- 1.00 and after treatment 1.10 +/- 1.08. Hepatitis C
      virus ribonucleic acid after 12 weeks of treatment was non-detectable (early
      viral response achieved) in 72 (80%) patients. A strong relation was found
      between aspartate aminotransferase to platelet ratio index and Negative
      polymerase chain reaction with early virological response as only 2 (4.5%)
      patients with negative polymerase chain reaction at 12 weeks had aspartate
      aminotransferase to platelet ratio index > 1 (p = 0.001). CONCLUSIONS: APRI can
      act as a predictor of early viral response in patients with Hepatits C.

PMID- 23866436
TI  - Comparison of upper lip bite test with Mallampati test in the prediction of
      difficult intubation at a tertiary care hospital of Pakistan.
AB  - OBJECTIVE: To determine the accuracy of the Upper lip bite test and Mallampati
      test in predicting difficult endotracheal intubation. METHODS: The cross
      sectional study was conducted at the Aga Khan University Hospital, a tertiary
      care facility in Karachi, Pakistan. Between June 1,2007 and May 31, 2008, 324
      adult patients undergoing elective surgeries requiring general anaesthesia with
      endotracheal intubations were enrolled. Pre-operatively upper lip bite test and
      Mallampati test were performed for the assessment of airway by a specifically
      trained observer. Laryngoscopic view was rated by using Cormack and Lehane
      laryngoscopic grading once the patient was fully anaesthetised using standard
      anaesthesia technique. Completed data sheets were analysed using SPSS version 10.
      McNemar test and rank correlation coefficient were used to compare the upper lip
      bite test and the Mallampati test. RESULTS: Of the 324 patients, 56 (17.3%) were
      classified as cases of difficult intubation. Upper lip bite test showed
      significantly higher accuracy, positive predictive value and negative predictive
      value than the Mallampati test. Comparison of specificity, however, did not
      reveal any significant difference between the two tests. CONCLUSION: Upper lip
      bite test is an acceptable alternative as a single test to predict difficult
      intubation in addition to other tests of airway assessment for the prediction of
      difficult intubation.

PMID- 23866437
TI  - Morbidity and mortality following high order caesarean section in a developing
      country.
AB  - OBJECTIVE: To determine the morbidity and mortality associated with multiple
      (four and higher order) caesarean section. METHODS: A group of 92 women who had
      undergone four or more caesarean sections was compared with another group of 184
      women who had three or less such procedures at the obstetric unit of the
      University of Nigeria Teaching Hospital, Enugu, Nigeria, between January 1, 1999
      and December 31, 2007. The record were retrieved by trained staff and data was
      extracted using pre-tested forms. SPSS 15 and Z test were used for statistical
      analysis. RESULTS: There were a total of 1,755 caesarean sections out of which 92
      (5.24%) were higher order repeat caesarean. Three women had the 6th caesarean
      section, while one had her seventh. Women in the study group were three times
      more likely to have primary postpartum haemorrhage (p = 0.001); to spend more
      time on the operation table; and to receive blood transfusion (p = 0.001)
      compared to the control group. More neonatal morbidities were observed among the
      controls. Hypertensive disorder was the second most common indication for
      caesarean section in the control group. There was no clear difference in terms of
      hospital stay, pre-operative haemoglobin concentration, and caesarean
      hysterectomy in the two groups. No death was observed during the period.
      CONCLUSION: Higher order caesarean section was associated with increased maternal
      morbidity but there was no mortality. Every effort to reduce primary and repeat
      caesarean sections should be encouraged, as this will reduce the higher order
      caesarean section rate, especially in the developing world which places high
      premium on child-bearing and large family size. Counselling on different methods
      of contraception during visits to antenatal clinics must be done to limit family
      size.

PMID- 23866438
TI  - The comparative study of submucosal resection of nasal septum under local and
      general anaesthesia.
AB  - OBJECTIVE: To compare the outcome of submucosal resection of nasal septum under
      local and general anaesthesia. METHODS: The retrospective study was conducted at
      the Sindh Government Hospital, Korangi, Karachi, from November 2008 to June 2010.
      A total of 100 patients (50 male and 50 females) having unilateral or bilateral
      nasal obstruction with moderate deviation of the nasal septum and unilateral or
      bilateral inferior turbinate hypertrophy, undergoing surgical treatment were
      inducted. They were divided into two groups: 50 patients of either gender
      operated under local anaesthesia; and the rest who were operated under general
      anaesthesia. All these patient came for post-operative follow up in July and
      August 2010, and both groups were compared. SPSS 18 was used for statistical
      analysis. RESULTS: Of the 100 patients, there were 19 complications: 1 (5.26%)
      among those who had undergone local anaesthesia, and 18 (94.73%) among those who
      had been given general anaesthesia. Besides, in Group I, the cost of the drugs
      averaged Rs500 per patient, the average time consumed was 20 minutes, and
      bleeding at time of surgery was mild (10 to 15 ml). In Group II, the average cost
      of drug Rs1500 per patient, the average time consumed was 40 minutes, and
      bleeding at time of surgery was moderate (15 to 100ml). No mortality was seen in
      either group. CONCLUSION: Local anaesthesia was found to be a far more safe,
      effective and economical option for submucosal resection of nasal septum.

PMID- 23866439
TI  - Choice of contraceptive method among females attending family planning center in
      Hayat Abad Medical Complex, Peshawar.
AB  - OBJECTIVES: To identify the pattern and causes of making contraceptive choices
      among females attending family planning centre in Peshawar, Pakistan. METHODS:
      The simple observational study based on convenient sampling was conducted at the
      family planning centre of Hayatabad Medical Complex, Peshawar, from October to
      December, 2010. Included were 104 females who were asked about their
      contraceptive use and the reason for their decisions. The variable used for
      contraceptive choices, included effectiveness (against preventing pregnancy),
      easy availability, side effects of the method, general health issues, cost factor
      and permanence of the method. RESULTS: It was found that 49 (46.7%) females were
      currently using injectables; 18 (17.1%) pills; 18 (17.1%) IUDs; 19 (10.5%) tubal
      ligation; and 9 (8.6%) condoms. The major causes for making the choices were
      effectiveness (n = 32; 30.5%); easy availability (n = 19; 18.1%); side effects (n
      = 11; 10.5%); reproductive tract infections (n = 3; 2.9%); and cost factor (n =
      2; 1.9%). Respondents who choose more than one reason were 23.8% (n = 25). It was
      observed that 60% (n = 63) of respondents were first-time users, while the rest
      gave history of using some method in the past. Out of this proportion, pills and
      barrier method were used in most patients. Among the illiterate group of 35
      (55.2%) respondents, 18 (28.6%) chose injectables; 6 (9.5%) chose IUCDs; and 6
      (9.5%) tubal ligation. Similarly, 13 (20%) respondents from poor socio-economic
      group and 15 (22.9%) respondents from the middle group chose injectables.
      CONCLUSIONS: When given choices and balanced information about contraceptives,
      more women are likely to continue the method. Respondents from the lower
      socioeconomic and illiterate group chose injectables in high proportion due to
      their effectiveness and easy availability. Side effects of the method and health
      concerns were less considered, while the cost factor was the least considered.

PMID- 23866440
TI  - Promoting healthy workplaces--health pledges initiative at North Kirklees Primary
      Care Trust, NHS, England.
AB  - OBJECTIVE: To evaluate the effectiveness of health promotion activities targeting
      physical activity, healthy eating, smoking and stress management as a part of
      healthy workplace initiative at North Kirklees Primary Care Trust, England.
      METHODS: The quasi-experimental interventional study was conducted from April
      2005 to March 2006 and involved all the employees of the North Kirklees Primary
      Care Trust, England, who were willing to participate. Main interventions were;
      lunch-time walk, motivational interviews, counselling and support sessions from
      qualified dieticians, physical activity and smoking cessation advisors. Free
      occupational therapy sessions were provided at the workplace. Incentives like
      discounted vouchers for sports club and the gymnasium were also given. Pre- and
      post-intervention data was collected and analysed using SPSS version 17. RESULTS:
      Of the total, 57 (42%) pledged to undertake physical activity; 50 (37%) healthy
      eating; 20 (15%) mental and emotional well-being; and 8 (6%) to quit smoking.
      Statistically significant associations were found between different health
      promotion activities like physical activity (p = 0.004), healthy eating (p =
      0.003), stress management and stop smoking (p = 0.001) at the workplace.
      CONCLUSION: Workplace is a potentially valuable setting for health promotional
      activities for primary prevention and may facilitate lifestyle modification.

PMID- 23866441
TI  - Antiglycation activity of thiamin-HCl and benfotiamine in diabetic condition.
AB  - OBJECTIVE: To observe the antiglycation effect of water-soluble vitamin, thiamin
      hydrochloride (B1) and its fat-soluble derivative benfotiamine and their
      comparison with two different glycation assays in diabetics. METHODS: Plasma of
      both the normal's and diabetic persons was taken for this experimental study
      which was conducted in the Department of Chemistry and Biochemistry, University
      of Agriculture, Faisalabad in 2008. Varying concentrations of both the glycation
      inhibitors and glucose were incubated for 5 weeks at 37 degrees C. Thiobarbituric
      acid and periodate borohydride assays were used to measure the antiglycation
      activity. RESULTS: The increase in glycation was observed from 1st to 3rd week of
      incubation, while it decreased after the 5th week due to the formation of
      advanced glycation end products. CONCLUSIONS: It was observed that 10mM
      concentration of benfotiamine and 5mM and 1mM concentrations of thiamine
      hydrochloride produced fairly good response to decreased glycation. Comparison
      between two assays proved periodate borohydride to be more reliable and sensitive
      than thiobarbituric acid.

PMID- 23866442
TI  - Decision-making and involvement of women with previous C-section in choosing
      their mode of delivery.
AB  - OBJECTIVE: To determine the attitude and factors leading to decision regarding
      the mode of delivery in women with previous experience of C-section. METHODS: The
      cross-sectional study was conducted at Maternity Unit of Jinnah Postgraduate
      Medical Centre, Karachi, from January to August 2008, and involved 150 women with
      one previous C-section without any recurrent cause. All women had a parity of two
      or more. Women with more than one caesarean section and women who lost contact
      were excluded. The women were recruited from antenatal clinic and were briefed by
      medical professionals before the questionnaire was filled out. SPSS version 10
      and Chi square test were used for statistical analysis. RESULTS: Of the total 29
      (19.3%) preferred a repeat caesarean section, and 121 (80.7%) opted for the trial
      of scar. No significant difference was seen in the mode of delivery when the
      decision was taken by women alone or when it was taken jointly by doctors and
      women. When the decision was taken by doctors, there was significant difference
      in the mode of deliveries. The patients expressed satisfaction towards the
      information received. Previous associated factors, like negative birth
      experience, had an influence on decision-making regarding the mode of delivery.
      CONCLUSION: Decision by women is extremely important regarding their mode of
      delivery and should be respected. Psychological support during pregnancy may
      provide an alternative to caesarean section for women with previous negative
      experience.

PMID- 23866443
TI  - How VATS has changed the management of spontaneous pneumothorax in the 21st
      century.
AB  - OBJECTIVE: To: determine the outcome of patients having undergone Video Assisted
      Thoracoscopic Surgery (VATS) for spontaneous pneumothrox in terms of hospital
      stay, complications and recurrence. METHODS: The netrospective study included the
      review of 39 cases who had presented with spontaneous pneumothorax at the Aga
      Khan University Hospital, Karachi, Pakistan, between January 2001 to November
      2008 and had undergone video assisted thoracoscopic surgery (VATS). RESULTS: The
      duration of hospital stay (had a range of 3 to 9 days), and the length of chest
      tube in place (a range of 2 to 8 days), 2 (5.1%) patients developed recurrence
      after VATS while 3 (7.6%) patients developed bleeding post operatively requiring
      transfusion and 2 (5.1%) patients developed atelectasis requiring bronchoscopy.
      CONCLUSION: Compared with figures for thoracotomy data from other studies, it was
      seen that the length of hospital stay and chest tube placement with VATS was less
      than that for thoracotomy, and the overall cost as well as post-operative pain
      was also low. The rate of recurrence was however comparable to that after
      thoracotomy.

PMID- 23866444
TI  - Offspring sex ratios among male tobacco smokers in Khartoum, Sudan.
AB  - OBJECTIVES: To explore any association between paternal tobacco smoking and the
      offspring secondary sex ratio, as well as the effect of duration and intensity of
      smoking on gender ratio. METHODS: The cross-sectional study was conducted around
      major public areas within Khartoum, Sudan, between August and September 2008 and
      involved 458 married Sudanese males with offsprings. The sample consisted of 111
      (24.2%) smokers and 347 (75.8%) non-smokers who were evaluated using a
      questionnaire on their offspring gender. Data on duration and intensity of
      smoking was also collected from the smokers' group. SPSS 16 was used for
      statistical purposes. Chi-square test was used to test for significance of
      associations between variables. Analysis of variance (ANOVA) was used to test for
      significance between ratios. RESULTS: The number of cigarettes smoked in males
      increases the likelihood of having a male offspring. The gender ratio in non
      smokers was 1.11, while it was 1.15 in smokers. CONCLUSION: Paternal smoking
      increases the offspring sex ratio.

PMID- 23866445
TI  - Efficacy of itraconazole versus fluconazole in vaginal candidiasis.
AB  - OBJECTIVE: To compare the efficacy of fluconazole 150mg single dose and
      itraconazole 200mg twice for one day in the treatment of acute vulvovaginal
      candidiasis. METHODS: The study was carried out at the Department of Dermatology,
      PNS Shifa Hospital, Karachi, from March, 2008 to February 2009 and comprised 60
      women with clinical and mycological diagnosis of vaginal candidiasis. Diagnosis
      was based on history, clinical examination and relevant investigations. The women
      were divided into two equal groups. After initial assessment, Group 1 was treated
      with capsule fluconazole 150mg stat, and Group 2 with capsule itraconazole 200mg
      twice for one day. They were assessed clinically for cure and relapse on day 7
      and 21 respectively. All findings were recorded in the proforma. Data was
      analysed using SPSS 12. RESULTS: The overall clinical evaluation showed 70% (n =
      21) cure rate with itraconazole and 50% (n = 15) with fluconazole. In Group-1, 7
      (23.33%) and in Group-2 8 (26.6%) showed some improvement, while 2 (6.66%) in
      Group 1, and 7 (23%) in Group 2 failed to respond. Relapse was observed in 9
      (28.5%) and 16 (53%) of the cured cases in Group 1 and Group 2 respectively.
      CONCLUSION: Itraconazole was found to be more effective in the treatment of
      vulvovaginal candidiasis compared to fluconazole with high cure and low relapse
      rate.

PMID- 23866446
TI  - Diagnostic accuracy of magnetic resonance cholangio-pancreatography in evaluation
      of obstructive jaundice.
AB  - OBJECTIVE: To determine the diagnostic accuracy of magnetic resonance cholangio
      pancreatography in the evaluation of obstructive jaundice taking endoscopic
      retrograde cholangio-pancreatography (ERCP) as the gold standard. METHODS: The
      cross-sectional study was conducted at the Radiology Department of the Sindh
      Institute of Urology and Transplantation from August, 2009, to February, 2010. It
      comprised 77 patients (36 males and 41 females) with clinically obstructive
      jaundice referred for magnetic resonance cholangio-pancreatography evaluation.
      The findings were compared with the gold standard. Data was analysed using SPSS
      version 15. RESULTS: The sensitivity of magnetic resonance cholangio
      pancreatography for obstructive jaundice was 97%; specificity was 75% and
      accuracy was 80%, while positive predictive value (PPV) and negative predictive
      value (NPV) were 99% and 60% respectively. CONCLUSION: Magnetic resonance
      cholangio-pancreatography is a relatively quick, accurate and non-invasive
      imaging modality for the assessment of obstructive jaundice in ruling out
      potentially correctable underlying causes and reducing unnecessary invasive
      interventions.

PMID- 23866447
TI  - Experience of caregivers with the survivors of hepatitis C.
AB  - OBJECTIVES: To assess and describe the experiences of those caring for hepatitis
      C patients in Karachi, Pakistan. METHODS: Using a qualitative approach, the study
      adopted a descriptive exploratory design for which 8 caregirers were selected
      through snowball sampling technique from different parts of Karachi. Data was
      collected between May and July 2010 through semi-structured interviews from the
      caregivers. The interviews were recorded on tape and were transcribed verbatim.
      The data was manually analysed for extracting themes and categories. RESULTS: The
      analyses of data led to one theme--'deadly, dangerous, and devastating. Two
      associated categories could also be noted: 'perceptions and misperceptions of the
      caregivers about hepatitis C' and 'challenges and adversities of the disease'.
      CONCLUSION: The diagnosis of hepatitis C had a profound impact on patients' and
      the caregivers' wellbeing. Although to some extent, caregivers were found to have
      fulfilled their role, but it was evident that better disease knowledge, funds and
      social support could have further helped them to address issues related to the
      disease.

PMID- 23866448
TI  - Comparison of the C14 urea breath test and histopathology in the diagnosis of
      Helicobacter pylori in the elderly.
AB  - OBJECTIVES: To compare the sensitivity and specificity of C[14] urea breath test
      with histopathological findings in biopsies obtained through endoscopy. METHODS:
      In this cross-sectional study, conducted at the Medical Faculty Ankara
      University, Ankara, Turkey between January and October 2009, 100 patients aged 65
      and above who fulfilled the criteria for inclusion were enrolled. Oesophago
      gastroduodenoscopy was carried out on the patients after eight hours of fasting,
      using a Fujinon endoscope, by the same expert. C14 urea breath tests were carried
      out on all patients with a capsule containing 37 kBq(1micro Ci) C14 urea/citric
      acid. Evaluation of all data was carried out using SPSS 11.5. Categorical
      variables were compared through Pearson Chi squared or Fisher's exact test. P <
      0.005 was taken as statistically significant. RESULTS: The average age of the
      patients was 71 +/- 5 years; 43 (43%) were male; and 57 (57%) were female.
      Helicobacter pylori positivity was found to be 35 (35%) in histopathological
      evaluation, and 36 (36%) in the C14 urea breath test. Of the 35 patients, 32
      (91.4%) were found to be positive by the C14 urea breath test also. Of the 65
      patients who were found to be negative on histopathology, 61 (93.8%) were also
      found to be Hp negative by the C14 urea breath test, and 4 (6.2%) were evaluated
      as false positive. A statistically significant correlation (p < 0.001) was found
      between histopathological and C14 urea breath test results. Compared with
      histopathology, the sensitivity of the urea breath test was 91.4%, and its
      specificity was 93.8%. A statistically significant (p < 0.001) relationship was
      found between histopathological results and the results of the C14 urea breath
      test. CONCLUSION: The sensitivity and specificity of the C[14] urea breath test
      in the group of elderly patients selected was high. The C14 urea breath test can
      be considered in the elderly group for diagnosis of Helicobacter pylori
      infection.

PMID- 23866449
TI  - Pain assessment and management in different wards of a tertiary care hospital.
AB  - OBJECTIVE: To assess the pain management by medical team, emergency room (ER)
      team and Acute Pain team in a tertiary care hospital. METHODS: The cross
      sectional study was done in Medical Ward, Surgical Ward and Emergency Room of Aga
      Khan University, Karachi, in March-April 2010. The assigned research medical
      officer visited the three locations every day and selected patients by way of
      convenient sampling. The study comprised 75 patients; 25 each in three groups.
      Information was collected on patient's demographics, general characteristics,
      type of drugs and modalities used. Specific queries about pain were sorted out
      like adequacy of pain assessment done by primary physician, pain intensity, any
      intervention done and pain relief post-intervention. SPSS version 17, analysis of
      variance and Chi square test were used for statistical purpose. RESULTS: The mean
      current pain score on the visual analogue score (VAS) was lowest in the Surgical
      Ward which was being managed by the Acute Pain Management Service (APMS) team
      followed by the Medical Ward and then Emergency Rooms. The difference was found
      to be statistically significant. The mean of worst pain score was also the lowest
      in the Surgical Ward. There was significant difference between wards in terms of
      the use of pain medications. Proper documentation for pain was done for all
      patients in the Surgical Ward, followed by the Emergency Room and then the
      Medical Ward. CONCLUSION: Better pain assessment, re-assessment, documentation
      and patient satisfaction were observed in the Surgical Ward compared to the other
      two locations of the study.

PMID- 23866450
TI  - New intrauterine growth percentiles: a hospital-based study in Istanbul, Turkey.
AB  - OBJECTIVE: To develop gender and gestation-specific growth percentiles for
      singleton live-born neonates and to compare new weight for age unisex percentiles
      with Lubchenco unisex percentiles. METHODS: Cross-sectional birth data were
      collected from the neonatal registry from January 2000 to April 2006 (n =
      15.509). After exclusion, the sample included 15.112 neonates. RESULTS: Newly
      developed weight for age, charts were compared with Lubchenco unisex percentiles,
      91.8% of the subjects were classified in the same way (Kappa = 0.74, P < 0.001).
      Small for gestational age (SGA) and large for gestational age (LGA) according to
      the Lubchenco percentiles differed from the new percentiles (Mc Nemar test, P <
      0.001). The percentage of SGA neonates was underestimated by Lubcheno percentile
      (5.8% vs. 10.6%, respectively), whereas the percentage of LGA neonates was
      overestimated by Lubcheno percentile (10.3% vs. 9.3%, respectively). CONCLUSION:
      New growth chart for newborn delivered at different gestational ages have been
      established, which can be used to define SGA and LGA in Turkish neonates. Studies
      comparing the Lubchenco percentiles with new percentiles are needed.

PMID- 23866451
TI  - Situation analysis of child labour in Karachi, Pakistan: a qualitative study.
AB  - In Karachi, large employment opportunities, burgeoning population and the
      availability of cheap labour might be the contributing factors for the increasing
      prevalence of child labour. A literature review was conducted in 2007 that
      included published and unpublished literature since 2000. Various organizations
      working in the field were also covered, while the perception of the child
      labourers was covered through three focus group discussions. Common health issues
      among the child labourers in Karachi included respiratory illnesses, fever and
      generalised pains, as well as drug and sexual abuse. Organisations working for
      child labour could be broadly categorised into those working for legal advice and
      advocacy; those generating statistics; and those that are providing
      interventions. Discussion with children showed that irrespective of the immediate
      cause, the underlying determinant for child labour was poverty. The best
      practices identified included evening schools and drop-in centers for working
      children with provision for skill-based education and basic health facilities.
      There is need to have more such centres.

PMID- 23866452
TI  - Role of community health nurse in earthquake affected areas.
AB  - The role of Community Health Nurses (CHNs) outside the traditional hospital
      setting is meant to provide and promote the health care needs of the community.
      Such nurses can play a substantial role in the community setting including
      emergencies like disasters. This became evident after the earthquake of October
      8, 2005 in Pakistan. The objective was to address the issues, faced by primary
      healthcare providers working in earthquake-affected areas focusing on
      participatory approach. The experience of the interventions done by CHN by a
      guided frame work (assessment, planning, implementation and evaluation
      components) is described. Issues identified by CHN included: lack of training of
      health care providers, lack of collaboration, communication between the medical
      and management staff due to poor infrastructure of the healthcare facilities. The
      interventions were carried out, utilizing existing resources. Efforts were
      directed to build capacity of health care providers at grass root level to fill
      in gaps of health care delivery system for sustainable change. Overall, working
      in the earthquake affected areas is challenging. Health leadership should foresee
      role of CHN in emergencies where quality healthcare interventions are essential.

PMID- 23866453
TI  - Bilateral ectopic ureters with bladder agenesis.
AB  - Agenesis of Urinary bladder is an extremely rare congenital genitourinary anomaly
      and is associated with other severe malformations that are incompatible with
      life. About 60 cases and 22 live births only have been reported in English
      literature. We report an eight year old girl with triad of complete agenesis of
      bladder and urethra, solitary functioning left kidney and an ectopic ureter
      opening into the vagina. The management of the child along with embryo
      pathogenesis and literature review is discussed.

PMID- 23866454
TI  - Dermatofibrosarcoma protuberans: an unusual case of neck swelling.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a relatively intermediate to low grade
      malignant tumour with high proclivity for local recurrence if excised
      inadequately. It is a locally aggressive tumour and despite sharing some
      histological features with fibrohistiocytic tumours, it tends to grow in a more
      infiltrative manner. We are reporting this rare tumour in a 30-year-old woman
      where the diagnosis of DFSP was confirmed histologically and by positive
      immunomarkers at immunohistochemistry.

PMID- 23866455
TI  - Topiramate induced sudden loss of vision.
AB  - The case of a 20 year old female presenting with overnight acute loss of vision
      is reported. The patient was recently started on topiramate (Hitop) for her
      recurrent migraine and developed sudden loss of vision due to acute myopia.
      Topiramate was discontinued and the patient's vision returned to normal. Delayed
      and incorrect treatment may result in permanent vision loss, secondary to angle
      closure glaucoma; therefore it is imperative that prescribing physicians are
      aware of this rare but serious ocular emergency.

PMID- 23866456
TI  - Anaesthetic management of neonatal primary hyperparathyroidism.
AB  - Neonatal primary hyperparathyroidism (NPHP) is a rare disease that presents in
      the first 6 months of life. It is almost invariably fatal unless a prompt
      diagnosis is made and urgent surgical intervention is instituted. Patients with
      hyperparathyroidism require special preoperative considerations. They require
      proper work-up from cardiac, renal and neurological point of view, correction of
      intravenous volume and electrolytes irregularities. We are presenting a case of
      an infant who started to have cyanosis and lethargy at 21st day of life. Initial
      diagnosis of pneumonia was made but later on diagnosed as hyperparathyroidism. He
      was planned for parathyroidectomy under general anaesthesia. He was induced with
      sevoflurane followed by fentanyl and atracurium and intubated with size 3.5 mm
      endotracheal tube (ETT). Later, he was maintained with isoflurane and O2/NO2. He
      was successfully extubated at the end of operation and was shifted to intensive
      care unit (ICU) for close monitoring.

PMID- 23866457
TI  - Laparoscopic splenectomy for haematological disorder: our experience.
AB  - Laparoscopic splenectomy has universal acceptance due to less morbidity and
      decreased incidence of peroperative and postoperative complication. It is not a
      popular procedure in Pakistan due to technical challenges. Here, we are
      presenting our experience of laparoscopic splenectomy for haematological
      disorders at Aga Khan University Hospital. A total of seven cases, underwent
      elective laparoscopic splenectomy for haematological disorders. The operative
      time was less than 3 hours with minimal blood loss with rapid and uneventful
      recovery. There was no procedure related morbidity or mortality; however, one
      patient expired due to overwhelming post splenectomy sepsis. Our initial report
      highlights the safety of laparoscopic splenectomy and we propose it to be the
      procedure of choice in elective splenectomy.

PMID- 23866458
TI  - MRI findings in methanol intoxication: a report of three cases.
AB  - Methanol is a highly toxic substance and acute methanol poisoning produces severe
      metabolic acidosis and serious neurological symptoms, including severe visual
      impairment, extrapyramidal signs and coma. We present three cases of accidental
      methanol intoxication and discuss the MRI findings.

PMID- 23866459
TI  - Medical educational: the development of intellect.

PMID- 23866460
TI  - Are robots any better in stroke rehabilitation?

PMID- 23866461
TI  - Basic guide to scientific writing.

PMID- 23866462
TI  - Road rage and road side accidents involvement in commercial vehicle drivers of
      Faisalabad.

PMID- 23866463
TI  - Stress, job satisfaction and work hours in medical and surgical residency
      programmes in private sector teaching hospitals of Karachi, Pakistan.
AB  - OBJECTIVE: To assess stress levels, job satisfaction and working hours of the
      residents in Medicine and Surgery and to explore a correlation among the three
      factors. METHODS: The questionnaire-based. Cross-sectional study was conducted in
      2011 at two tertiary level teaching hospitals in Karachi, Pakistan (Ziauddin
      University Hospital and Aga Khan University Hospital, Karachi, Pakistan). The
      study population comprised 176 residents, General Health Questionnaire-12 was
      used to assess the mental health of the residents and a standardised Job
      Satisfaction Survey tool was used to assess their work satisfaction. RESULTS: A
      total of 176 residents participated in the study; 115 (65%) from Medicine, and 61
      (35%) from surgery. Of the total residents, 99 (56.3%) were under stress, and
      there was no significant difference in stress between Medicine and Surgery
      residents. Besides, 133 (75.6%) residents reported to be satisfied with their
      jobs. There was a statistically significant difference in job satisfaction
      between Medicine and Surgery residents (p < 0.001). Mean number of working hours
      per week reported by Medicine and Surgery residents were 74.82 +/- 15.95 and
      92.07 +/- 15.91 respectively (p < 0.001). A positive correlation of mean working
      hours with both stress (p = 0.009) and job satisfaction (p = 0.029) was found.
      CONCLUSIONS: Medicine and Surgery residents tend to differ on mean working hours
      and job satisfaction. The greater mean working hours of the residents could be a
      possible reason for increased stress and decreased job satisfaction among the
      residents.

PMID- 23866464
TI  - Contegra valved conduit in the paediatric population: an exciting prospect for
      right ventricle to pulmonary artery reconstruction; experience and outcomes at
      Aga Khan University.
AB  - OBJECTIVE: The focus of this study is to share the experience and outcomes of
      Contegra graft implantation in the paediatric and adult population in Pakistan.
      METHODS: Between May 2007 and July 2011, 16 patients, underwent implantation of a
      Contegra valved conduit. All operations were performed through a median
      sternotomy with cardiopulmonary bypass. Indications included: Pulmonary atresia
      with ventricular septal defect (n = 11), Tetralogy of Fallot with absent
      Pulmonary Valve (PV) syndrome (n = 2), double outlet right ventricle,
      transposition of great arteries and pulmonary stenosis (n = 1), isolated aortic
      valve disease (n = 1) and a pseudo-aneurysm with infective endocarditis (n =
      1).Conduit sizes varied between 16-22 mm. RESULTS: The three in hospital deaths
      were unrelated to the Contegra valved conduit. One patient was lost to follow up.
      Of the 12 survivors, 10 are currently free from re-operation or complications
      related to the conduit while one needed distal pulmonary artery dilatation owing
      to critical stenosis and another had severe Valvular regurgitation.
      Echocardiographic evaluation of the Contegra valved conduit demonstrated no
      haemodynamically significant valve regurgitation in 10 patients. CONCLUSION: In
      this small review of 16 operations using the Contegra valved conduit for Right
      Venticular Outflow Tract (RVOT) reconstruction in the paediatric population, we
      observed good post operative results concerning conduit function. The Contegra
      conduit provides an excellent substitute to the homograft with satisfactory early
      and mid-term results though long-term results are awaited in Pakistan.

PMID- 23866465
TI  - Subclavian steal syndrome secondary to subclavian artery thrombosis in a patient
      with homocysteinemia and its successful treatment.
AB  - Subclavian steal syndrome (SSS) is a rare condition. It results from subclavian
      artery (SA) stenosis proximal to the origin of the vertebral artery. It is
      characterized by cerebral ischaemia with associated symptoms of vertebrobasilar
      hypoperfusion and/or symptoms of brainstem or arm ischaemia. We describe a case
      of a 35 year old male who presented with persistent vertigo for two months, blue
      discoloration and pain in the left fingers for two weeks. A diagnosis of SSS was
      made and patient was treated with a gortex graft from the arch of the aorta to
      the second portion of the left subclavian artery. Treatment is aimed at restoring
      permanent antegrade blood flow to the affected vertebral artery. This abolishes
      vertebral basilar symptoms and other manifestations of SSS. Several modalities
      exist, however surgical correction is the treatment of choice.

PMID- 23866466
TI  - Rituximab therapy for flare-up of rheumatoid arthritis after total knee
      replacement surgery.
AB  - A variety of drug types are used alone or in combination to manage Rheumatoid
      Arthritis along with physiotherapy. We report herein the case of a 51 year old
      female patient with a history of Rheumatoid Arthritis whose disease remained
      active despite being on routinely used multiple disease modifying antirheumatic
      drugs. The patient underwent bilateral total knee arthroplasty with subtotal
      synovectomy due to the severe pain caused by her concomitant age related
      osteoarthritis which was only aggravated by her active rheumatoid arthritis
      disease. Three months following surgery, the patient's knee pain with typical
      rheumatoid flare and swelling reappeared for which a B cell monoclonal antibody,
      rituximab, was given. Her number of tender and swollen joints reduced to less
      than three and her C-reactive protein levels and erythrocyte sedimentation rate
      reduced significantly along with considerable improvement in her Global
      Assessment score. Her severity of pain also decreased to 3 from an initial score
      of 8 on the Visual Analog Scale. Thus, Rituximab helped improve our patient's
      symptoms from recurrence of synovitis after total knee replacement.

PMID- 23866467
TI  - Telemedicine--the need of time.

PMID- 23866468
TI  - Hepatic osteodystrophy: a relationship between osteoporotic bone and chronic
      liver disease.

PMID- 23866469
TI  - Systemic lupus erythematosus: to suffer or not to suffer?

PMID- 23866470
TI  - Haemovigilance.

PMID- 23866471
TI  - Is there any benefit of preoperative oral trimetazidine in coronary artery bypass
      graft?
AB  - OBJECTIVE: To evaluate the impact of preoperative oral trimetazidine on
      myocardial protection in coronary bypass surgery. METHODS: We conducted a
      prospective double blind randomized study in the Department of Cardiac Surgery,
      Chaudhry Pervaiz Elahi (CPE) Institute of Cardiology, Multan, Pakistan. One
      hundred and seventy (170) patients of isolated CABG were included in the study.
      All operations were done by conventional technique of CABG using cardiopulmonary
      bypass, moderate systemic hypothermia and cold antegrade blood cardioplegia. The
      patients were randomized into 2 groups i.e. Group 1 (n = 85), who received and
      Group 2 (n = 85), who did not receive Trimetazidine. Trimetazidine (20 mg) was
      given orally, at 10:00 pm the night before operation and also at 7.00 am on the
      day of surgery. The CPK and CK-MB levels were determined before operation,
      immediately after shifting to the ICU, 12 hours and 36 hours after the operation.
      The comparison of CPK and CK-MB levels was carried out using analysis of variance
      with repeated measures. The peri-operative clinical and laboratory data were
      compared using Student's t-test for numeric variables and Chi-square test for
      categoric varaibles. The difference was considered statistically significant if
      the p-value was < 0.05. RESULTS: The pre-operative variables i.e. age, gender,
      Canadian Cardiovascular Society (CCS) class, ejection fraction, diabetes, history
      of smoking, haemoglobin level, serum creatinine etc had no differences in both
      group. Both groups showed no significant difference in Cardiopulmonary Bypass
      time (BPT), Aortic cross Clamp Time (CxT), prevalence of intra-operative
      arrhythmia and need for inotropic support. The analysis did not show any within
      group or between groups differences in the CPK and CKMB levels. CONCLUSION: This
      study showed that oral Trimetazidine given before coronary bypass grafting did
      not provide any benefit in myocardial protection.

PMID- 23866472
TI  - To compare the outcome (early) of neonates with birth asphyxia in-relation to
      place of delivery and age at time of admission.
AB  - OBJECTIVE: To determine the frequency of birth asphyxia and short-term (early)
      outcome in relation to age at admission and place of delivery. METHODS: A
      descriptive cross-sectional study was conducted in the Paediatric Department,
      Neonatal Ward of Liaquat University Hospital (LUH) Hyderabad from January to
      December 2009. All babies were received at our nursery or delivered in LUH with
      birth asphyxia were included, while babies having major congenital abnormalities,
      with birth weight < 1800 gm or preterm were excluded. After consent and
      enrollment their detailed history including peri-natal history, Apgar score,
      resuscitation measures, problems and outcome were recorded on a pre-designed
      study proforma. Short-term outcome was measured after 7 hours as clinically
      improved, developed neurological disability (Hypoxic Ischaemic Encephalopathy
      stage II or III) or death. RESULTS: The frequency was (n = 600; 25%) of LUMHS
      born and (n = 310; 61.63%) were received within 6 hours, (n = 272 45% were LUMHS
      born and n = 7 7% were out born), (n = 37; 38.95%) within 24 hours and (n = 9;
      10.3%) after 24 hours. On initial neurological evaluation (n = 90; 15%) were
      normal while clinical signs of HIE were present in 85%, with (n = 180; 30%) in
      stage I, (n = 210; 35%) in Stage II and (n = 120; 20%) in stage III of HIE.
      Outcome was measured after 72 hours, around 53.3% (320) were normal, 31.6% (190)
      developed neurological disability, while 15% (90) babies expired. Outcome was
      better in Liaquat University of Medical Health Sciences (LUMHS) born than out
      born with statistically significant difference in terms of disability (Chi-square
      test P-value < 0.0001) but no difference was noted in terms of disability to
      death. There was a statistically improved outcome for babies received within 6
      hours than those after 6 hours of birth (Chi-square test P-value < 0.0255).
      CONCLUSION: Early recognition of birth asphyxia and timely referral to tertiary
      center can reduce morbidity and mortality.

PMID- 23866473
TI  - Coronary artery disease in critical patients of Iran.
AB  - OBJECTIVE: To identify the risk factors for Coronary Artery Diseases (CAD), such
      as hypertension, hyperlipidaemia, smoking, age, obesity, immobility and diabetes
      mellitus, in critical patients of Sistan-Baluchistan (SB), Iran. METHODS: This
      cross-sectional research was performed in 2006. The sampling method was
      convenience, and involved 616 hospitalised patients in the CCUs of hospitals of
      Sistan-Baluchistan province. Data was collected by structured interview and a
      checklist which included personal characteristics and risk factors like
      lifestyles as well as biochemical and physiological factors for CAD. SPSS
      software, Chi-square and exact fisher tests were used for analysis. RESULTS:
      Frequency of risk factors among patients with CAD was found to be high in the
      study area. Also, the results showed that the prevalence of some risk factors,
      such as diabetes mellitus 198 (32.5%), hypertension 266 (43.7%) and obesity 131
      (22.9%), was significantly higher in women than men. Besides, there was a
      significant relationship between smoking, 317(52.3%) and low mobility 503
      (83.3%), with gender (p = 0.001). CONCLUSION: Clinical and para-clinical data
      indicated that the adult population has a high level of CAD risk factors in the
      Sistan-Baluchistan province which may require urgent steps to address national
      control measures regarding CAD. Implementation of a prevention programme is
      necessary in order to reduce the risk factors. Also, health education is
      necessary, specially for women.

PMID- 23866474
TI  - Effect of oral clonidine on acute intraocular pressure rise after cataract
      extraction under general anaesthesia.
AB  - OBJECTIVE: To evaluate the efficacy of preoperative oral clonidine (5 g/kg) in
      preventing ocular hypertension in the early period after cataract surgery with
      posterior chamber intraocular lens implantation under general anaesthesia.
      METHODS: This was a randomized double-blind clinical trial comprising of 62 eyes
      in 62 patients with senile cataract without using any viscoelastics. They were
      randomly assigned into two groups for preoperative oral clonidine (5 g/kg) and
      placebo. Intraocular pressure (IOP) was measured 6,12 and 24 hours
      postoperatively. RESULTS: Mean differences of lOPs at 6 and 12 hours after
      surgery were significantly lower in clonidine group [+0.41 4.55 (p = 0.612), 0.06
      3.62 (p = 0.922)] than placebo group [5.77 4.25 (p = < 0.001), 4.70 3.19p <
      0.001)] but was more than preoperative intraocular pressures in both. There was
      no statistically significant difference between the mean IOP 24hours post
      operatively in the two groups. But compared to preoperative IOP less increase in
      mean IOP was seen in clonidine group when compared to placebo group. CONCLUSION:
      A single dose of oral clonidine (5 g/kg) preoperatively can produce a significant
      IOP-lowering effect in early period after cataract surgery, specially in the
      first 12 hours.

PMID- 23866475
TI  - Determination of growth pattern of 7-12 years old children in YAZD city and
      comparison of it with WHO standards.
AB  - OBJECTIVE: To assess the growth pattern of children in Yazd, and compare it with
      standards outlined by the World Health Organisation. METHODS: The cross-sectional
      study, which was conducted in 2009, involved 20 guidance schools of Yazd city. A
      total of 1921 children were chosen by simple cluster method and general
      demographic and anthropometric information regarding the subjects was extracted
      from students' health identification booklets. Data was analysed through SPSS.
      RESULTS: The mean values of height in 7th and 12th years of age were 119 +/-
      8.8cm and 150 +/- 6.6cm in boys and 117 +/- 5.97cm and 152 +/- 7.3cm in girls
      respectively. The mean values of weight in 7th and 12th years of age were 20 +/-
      3.39kg and 39 +/- 1kg in boys and 20 +/- 3.78kg and 41 +/- 1.07kg in girls
      respectively. These values generally were below the values set by the World
      Health Organisation till the 9th year of age, and above them beyond the 9th year.
      CONCLUSION: The growth pattern among children in Yazd is better than some of the
      other provinces in Iran. Larger studies are needed for generating Iran-specific
      standard for better assessment of the growth and nutritional status of Iranian
      children.

PMID- 23866476
TI  - What method of contact works best for recruiting participants in a study: lessons
      for health care researchers?
AB  - OBJECTIVES: To assess the various recruitment strategies used by medical
      researchers and their response rates. METHODS: The observational study, part of a
      larger retrospective cohort, was done at the Aga Khan University Hospital,
      Karachi, Pakistan, from May 2008-December 2010, covering a period from 1999 to
      2005. We used a multi-mode contact approach for including participants in the
      study. This comprised an invitational letter that described the study sent along
      with a mail-back, postage-paid envelope and multiple phone calls for recruitment
      of participants. The response to each mode was noted and described as frequency
      and percentage. RESULTS: There were 1335 participants eligible for recruitment in
      the study. Of them, 1247 (93.4%) were sent mailouts to which only 84 (6.7%)
      responded. Besides, 1133 participants,whose phone numbers were available, were
      called. Overall, the number of people that we were able to contact was low. The
      response to postage paid mail was very poor whereas the majority of participants
      were contacted via phone calls. Out of such participants, 257 (19.25%) agreed to
      participate at the very first call and our results suggest that more than three
      calls made very little contribution to the consent rate. CONCLUSION: Recruiting
      subjects from contact information available in the medical records may not be the
      best method. Multiple and innovative approaches are required for approaching
      potential participants and requesting them to participate in a study.

PMID- 23866477
TI  - Safety and efficacy of transurethral pneumatic lithotripsy for bladder calculi in
      children.
AB  - OBJECTIVE: To determine the safety and efficacy of transurethral pneumatic
      lithotripsy for bladder calculi in children. METHOD: The study included 100
      children up to 15 years of age undergoing pneumatic cystolithoclast for bladder
      stones. The descriptive study was conducted from September 2006 to February 2007
      at the Sindh Institute of Urology and Transplantation, Karachi. The inclusion
      criteria was children up to 15 years of age with a bladder stone of up to 3cm,
      pre-operative negative urine culture, no coagulopathy and fit for general
      anaesthesia. An X-ray and ultrasound of Kidney and Urinary Bladder (KUB) was
      mandatory. The procedure was done under general anaesthesia with a single dose of
      pre-operative antibiotic. A mini-scope of 4FR or a semi-rigid ureteroscope of
      7/8.5 FR with pneumatic wolf lithoclast was used for the fragmentation of stones.
      Duration of procedure, any per-operative and post-operative complications and the
      duration of hospital stay were recorded. Post-operatively, the patient underwent
      ultrasound Kidney and Urinary Bladder at the first follow-up to assess stone
      clearance after one week. RESULT: Mean patients age was 4.95 +/- 3.3 years. The
      male-to-female ratio was 11.5: 1 The mean hospital stay was 9.2 +/- 2.5 hours.
      The mean operating time was 25 (10 -65) minutes. Ten (10%) patients developed
      minor complications out of which 5 (5%) developed haematuria and 4 (4%) developed
      difficulty in passing urine. One (1%) of the patients developed post-operative
      retention of urine. All the patients were stone-free after the procedure.
      CONCLUSION: The transurethral pneumatic lithoclast is very effective and safe in
      children with bladder stones up to 3cm.

PMID- 23866478
TI  - Laparoscopic total extra-peritoneal inguinal hernia repairs by a surgeon
      experienced at laparoscopic cholecystectomy.
AB  - OBJECTIVE: To measure standards achieved at total extra peritoneal hernia repair
      by a surgeon experienced in laparoscopic cholecystectomy, and to compare the
      results with standards identified by the National Institute for Clinical
      Excellence. METHODS: The outcomes of the first 100 consecutive total extra
      peritoneal hernia repair cases by the surgeon were retrieved retrospectively. The
      surgeries were conducted between January 2006 and July 2007. Data was collected
      14 to 17 months post-surgery. RESULTS: All patients were men with a median age of
      58 years, ranging from 20 to 91 years. The maximum operating time was 75 minutes,
      while the minimum was 30 minutes. The conversion rate was 3% (n = 3) and the
      recurrence rate 4% (n = 4). Complications experienced included a chronic groin
      pain and one umbilical port-site haematoma. CONCLUSION: Though related to a
      single-surgeon experience, the study highlighted reduced preceptorship due to
      previous laparoscopic skills that were transferable. Patients should have a
      choice to opt for either open or laparoscopic inguinal hernia repair.

PMID- 23866479
TI  - The relationship between periodontal disease severity and state-trait anxiety
      level.
AB  - OBJECTIVE: To determine the relationship between the paroxysm related to
      periodontal disease and the state-trait anxiety level in patients attending a
      periodontology clinic in Turkey. METHODS: The cross-sectional study involved 141
      patients > or = 18 years old attending the periodontology clinic at the Dental
      Faculty of Erciyes University, Turkey, between January and March 2009. A
      questionnaire developed by the researchers, the State-Trait Anxiety Inventory
      Index and the Community Periodontal Index were used for data collection. SPSS 15,
      chi square test and unpaired students' t test were used for statistical analysis.
      RESULTS: Gingivitis was present in 101 (71.6%) patietns, while periodontitis was
      found in 40 (28.4%). The mean age of periodontal patients was significantly
      higher than those of gingivitis patients (p < 0.05). Graduates were less likely
      to develop periodontitis than those who had only primary education (p < 0.05).
      Gingivitis was seen to be significantly higher in patients having poor oral
      hygiene (p < 0.05). State-Trait Anxiety Inventory scores of periodontal patients
      was significantly higher than those of gingivitis patients (p < 0.05). Patients
      with high state anxiety scores were more likely to have periodontitis. The most
      important variables associated with periodontitis and gingivitis were age, State
      Trait Anxiety Inventory, income level and needs for treatment, respectively.
      CONCLUSION: Periodontal treatment will improve if anxiety is diagnosed and
      relieved by different methods.

PMID- 23866480
TI  - Countdown to 2015: a case study of maternal and child health service delivery
      challenges in five districts of Punjab.
AB  - OBJECTIVE: To identify the challenges confronting the Pakistan province of Punjab
      in delivering maternal and child health services at the district level. METHODS:
      The qualitative assessment was done from May 15 to June 15, 2010, comprising 5
      focus group discussions, 5 in-depth interviews with district managers, 49 in
      depth interviews with providers, and direct observation of 19 facilities
      providing comprehensive emergency obstetric care in the districts of Multan,
      Muzaffargarh, Bahawalpur, Khanewal and Jhelum. Using skilled birth attendance
      coverage as an indicator, Punjab districts were stratified into three socio
      economic strata, and from these the five-districts were selected. RESULTS:
      Distribution of basic emergency obstetric care facilities by population size was
      found to be inadequate in all districts. Quality of care was compromised by lack
      of staff and equipment. No anaesthetist was available in majority of the district
      hospitals and tehsil facilities. Half of the teshil headquarter hospitals were
      devoid of staff nurses. Vital medicines used in obstetric care were not
      available. Partograph was not being used in any of the tehsil-level facilities.
      Chlorine solution was not present in any of the facilities. Governance issues
      included multiplicity of command channels, delays in receipt of medicines and
      political interference. CONCLUSION: If the province has to achieve the related
      Millennium Development Goals (MDGs), related to maternal and child health, the
      existing facilities are not adequate. To achieve progress, proven and innovative
      approaches will have to be put in place that may influence the continuum of care
      from the household to the health facility.

PMID- 23866481
TI  - Screening immediate family members for carrier identification and counseling: a
      cost-effective and practical approach.
AB  - OBJECTIVE: To screen immediate family members of thalassaemia patients for
      carrier identification and counselling. METHODS: The cross-sectional study was
      conducted at an urban thalassaemia treatment and prevention centre in Karachi,
      Pakistan, from January to December 2008, and involved 188 siblings of 100
      thalassaemia patients. Complete blood count, including haemogram, was performed
      in the siblings. Samples with MCV < 75fl and MCH < 25% were subjected to
      haemoglobin-electrophoresis. Haemoglobin A2 of 3.5% to 7.0% was labelled as beta
      thalassaemia minor. Those with haemoglobin A2 of 3.0-3.4% but red blood cell
      count of > 4.5 x 1012/L were reported as equivocal and were screened for iron
      deficiency anaemia and a repeat haemoglobin A2 estimation was done on high
      performance liquid chromatography. Equivocal results of the chromoatography were
      screened for thalassaemia mutation. Mean values along with standard deviation
      were worked out for relevant variables. RESULT: Of the 188 subjects, there were
      124 (66%) males and 64 (34%) females. The mean age was 16.5 +/- 6.3 years (range:
      3 months to 30 years) and the mean family size was 1.88 +/- 3.8 (range: 1-12)
      children per family. There were 51 (51%) first-cousin marriages in this group. Of
      the siblings, 65 (34.5%) were identified as normal, while 117 (62.2%) were
      reported as beta-thalassaemia carriers. Six asymptomatic siblings were reported
      as consistent with beta-thalassaemia major. CONCLUSION: There were 62.2% siblings
      identified as beta thalassaemia carriers in the study as opposed to 5-8% carriers
      in the general population. We also identified six asymptomatic and unidentified
      cases of beta-thalassaemia intermedia in these families. Therefore, in our
      context where both resources and budgets are limited, it is practical to focus on
      siblings of identified thalasaemia patients.

PMID- 23866482
TI  - Perceived individual and community barriers in the provision of family planning
      services by lady health workers in Tehsil Gujar Khan.
AB  - OBJECTIVES: To identify contextual barriers (social, cultural, geographic and
      economic), faced by Lady Health Workers (LHWs) and to assess their strategies at
      different levels (individual, community and system) in the provision of family
      planning services to their clients in Tehsil Gujar Khan. METHODS: The mixed model
      cross-sectional study was conducted from April 1 to July 10, 2010, in Tehsil
      Gujar Khan, Punbjab, Pakistan. It was carried out in two phases: in the first
      phase 10 in-depth interviews were conducted with the workers, followed by two
      focus group discussions. On the basis of findings, a structured questionnaire was
      developed and administered to 111 workers in the second phase. Of the total, 97
      responses were used for analysis. Data analysis was done by SPSS-16. RESULTS:
      Majority of the respondents reported barriers at the community level: religious
      barriers 69% (n = 67), sociocultural barriers 58% (n = 56), transport 54% (n =
      52), communication and economic reasons 25% (n = 24). Individual level barriers
      were female gender, experience and low education. System-level barriers were
      increased workload, National immunization days/sub-national immunization days,
      late supply, stock shortage (especially injectables), problems for referred
      clients and lack of proper incentives. CONCLUSION: Lady health workers still face
      barriers at individual, family, community and system level in the delivery of
      Family Planning services.

PMID- 23866483
TI  - Emergency obstetric hysterectomy.
AB  - OBJECTIVE: To assess the frequency of obstetric hysterectomy, its indications and
      associated maternal and perinatal morbidity and mortality. METHODS: The
      retrospective observational analytical study was conducted at the Department of
      Obstetrics and Gynaecology, Unit-I, Jinnah Postgraduate Medical Centre, Karachi
      from January 2003 to December 2009. Records of all patients who had underone
      hysterectomy at the study centre during the study period were explored for age,
      parity, booking status indication and the type of operation performed. Maternal
      and foetal morbidity and mortality were also recorded. SPSS 13.0 was used for
      statistical analysis. RESULTS: Against the total 44,612 deliveries during the
      period, 121 hysterectomies were performed for obstetric indications. The
      frequency of the procedure, as such, was 1 in 368 (0.27%) deliveries. The major
      indications were ruptured uterus in 57 (47.1%), and severe postpartum haemorrhage
      due to atony of uterus in 35 (28.9%). Other indications included severe
      haemorrhage due to placental abnormalities in 14 (11.6%); placenta previa in 3
      (2.5%); abruptio placenta in 4 (3.3%); and severe infection following vaginal
      delivery in 3 (2.5%). Infection was the commonest complication seen in 14 (11.6%)
      patients. There were 11 (9.0%) maternal deaths and 65 (53.7%) perinatal deaths.
      CONCLUSION: Emergency obstetric hysterectomy remains a necessary tool for
      consultant obstetricians. Acting at the optimal time with clear judgment, and
      professional surgical technique can reduce morbidity and mortality in such cases.

PMID- 23866484
TI  - Evaluation of contributing factors of post transplant erythrocytosis in renal
      transplant patients.
AB  - OBJECTIVE: To evaluate the prevalence and contributing factors causing post
      transplant erythrocytosis in renal transplant patients. METHODS: This
      retrospective study was conducted on live related renal transplant patients at
      SIUT. The records of all transplant recipients transplanted between April 2008
      and December 2008 and who had at least 24 months follow up were studied. Patients
      in whom haematocrit exceeded 51% and those who received treatment for it were
      classified into post transplant erythrocytosis group. RESULTS: Out of 200 renal
      transplant patients who had functioning graft at the time of analysis, 40 (20%)
      developed post transplant erythrocytosis (HCT > or = 51%) after a mean interval
      of 9.5 +/- 2.5 months. Patients with erythrocytosis were mostly males (95% in PTE
      group vs 73.75% in non PTE group), had a shorter period on dialysis before
      undergoing renal transplantation (9.28 months in PTE group vs 14.56 months in non
      PTE group) and had relatively better graft function at the onset of
      erythrocytosis as judged by serum creatinine (S. Creatinine of 1.06 +/- 0.29
      mg/dl in PTE group vs 1.37 +/- 0.51 mg/dl in non PTE group). No thrombotic
      complications were observed. All patients with erythrocytosis were treated with
      enalapril (ACE inhibitors) and 28 out of 40 required phlebotomy in addition to
      ACE inhibitors. The mean HCT at the time of last follow up in treated patients
      was 48.61 +/- 1.85%. CONCLUSION: Post transplant erythrocytosis generally occurs
      in male patients with good graft function, thrombotic complications are of rare
      occurrence and response to ACE inhibitors is good.

PMID- 23866485
TI  - Nasolacrimal duct obstruction in children: outcome of primary intubation.
AB  - OBJECTIVE: To evaluate the outcome of nasolacrimal intubation as a primary
      treatment of congenital nasolacrimal duct obstruction (NLDO) in children up to 4
      years of age. METHODS: During the 3 years period from July 2008 to June 2011, in
      the Paediatric Ophthalmology Department. Alshifa Trust Eye Hospital, Rawalpindi,
      65 eyes of 59 children, aged 12 to 48 months with congenital NLDO and no prior
      Nasolacrimal duct surgery were enrolled. After written informed consent, all
      nasolacrimal intubations using olive tip silicon tube were performed under
      general anaesthesia. The planned tube retention was at least 3 months. The study
      outcome visit was timed 1 month after tube removal and treatment success was
      analyzed. Intra operative and post operative complications were also noted. Data
      were analyzed by SPSS 16. Frequencies and percentages were calculated for
      categorical variables. Mean +/- SD were computed for age and duration of
      intubation. Chi-square test was used to compare proportion of outcomes in
      different age groups and duration. RESULTS: The overall success rate of
      Nasolacrimal intubation as a primary treatment of congenital NLDO was 89% in
      children between 12 to 48 months age (mean 25.8 +/- 9.8 months). The success was
      92% in children under 2 years of age (P < 0.0001) and 90% in children between 2-3
      years of age (P < 0.0001). The procedure remained less successful in children
      between 3-4 years of age (P < 0.2860) as compared to children under 3 years of
      age. The success rate was consistently high (92.3%) when the tube was left in
      situ for more than 3-6 months (P < 0.0001). CONCLUSION: Nasolacrimal intubation
      with Olive tip silicon intubation tube is a successful procedure as a primary
      treatment of Nasolacrimal duct obstruction in children under 4 years of age.

PMID- 23866486
TI  - Spontaneous renal artery dissection: current perspective.
AB  - Spontaneous Renal artery dissection is a rare entity that may remain clinically
      silent or present with non-specific signs and symptoms, which makes it a
      diagnostic challenge. It may be associated with certain underlying vascular
      pathologies, but its occurrence remains idiopathic in the majority of cases.
      While there are no evidence-based guidelines for its management, blood pressure
      control and preservation of renal function remain the cardinal goals of therapy.

PMID- 23866487
TI  - Media created violence: a social determinant of mental health.
AB  - In today's high technological world, scientific discoveries contribute remarkable
      development to human life, but it could also have an adverse impact on mankind.
      Among all these advancements, media is one of the inventions which aims at
      capturing a countless group of viewers and transmit information via various
      mediums. Media violence is considered one of the hampering determinants which
      harms an individual psychologically. The primary goal of a health professional is
      to work for the maintenance of mental health. Therefore, it is imperative to
      create an understanding about the impact of media violence on mental health,
      particularly in the Pakistani context. Violence has become a major public health
      problem in Pakistan. The main cause of violence seems to be anger and frustration
      due to poverty, political conflicts, lack of education, and the overall
      governance approach in the country. Therefore, there is a prime need to think and
      work on this neglected area like conducting research and increasing public
      awareness, and to curb media violence.

PMID- 23866488
TI  - A pica case confused with renal and bladder stones.
AB  - Pica is considered as an eating-nutritional disorder in childhood and is
      generally analysed within obsessive-compulsive disorders. A 15-year-old female
      patient was admitted to the urology clinic with nausea, vomiting, and stomach
      ache. A 23 x 23 mm opacity was identified in left T-11-12 level in direct urinary
      graph. Full abdomen ultrasonography was reported to be normal. Later, it was
      learned that the patient had the habit of eating stone. The patient was diagnosed
      with obsessive-compulsive disorder following psychiatric consultation, and
      appropriate treatment was given.

PMID- 23866489
TI  - Primary pulmonary sarcoma metastasising to the skin during pregnancy.
AB  - Lung cancer during pregnancy is a rare situation which is being increasingly
      reported during the past two decades due to a rising trend of cigarette smoking
      among young women and the tendency to delay pregnancy to a later age in life. We
      describe the case of a 32-year-old woman with primary pulmonary sarcoma,
      diagnosed at 31st week of pregnancy. X-ray chest and thoracic magnetic resonance
      imaging revealed a 9 x 6 cm mass in the left mediastinum, with tracheal shift,
      and pleural effusion. Biopsy performed during broncoscopy, was reported as
      mesenchymal tumour. She delivered a baby by Caesarean section at the 32nd week of
      gestation due to the development of superior vena cava syndrome. A skin biopsy
      taken 3 weeks later from the nodular lesion at the periumblical region was
      reported as a tumour metastasis. She received radiotherapy for 10 days, but died
      in the intensive care unit. Malignancies, even those as uncommon as a pulmonary
      sarcoma, should be considered in the differential diagnosis of pleural effusion
      during pregnancy.

PMID- 23866490
TI  - Extra spinal osteoarticular tuberculosis: a case series of 66 patients from a
      tertiary care hospital in Karachi.
AB  - The demographic, clinical and laboratory data of patients diagnosed as extra
      spinal osteoarticular tuberculosis, presenting at Department of Orthopaedic
      Surgery, Abbasi Shaheed Hospital, Karachi Medical and Dental College, Karachi,
      between December 2006 and January 2009 were analysed. There were 66 patients
      registered for the study. Forty four (66.66%) patients were females. The mean age
      was 26.5 +/- 13.5 years. Swelling and pain were the commonest symptoms. Knee and
      hip were the most frequent sites involved. The mean time to diagnosis was 12.32
      +/- 18 months (range = 2- 96 months). Six (09.09%) patients had history of
      previous pulmonary kochs. Nine (13.63%) had concurrent pulmonary and 1(01.51%)
      had concurrent intestinal kochs. The average first hour ESR was 48 mm/h (16-102).
      Manteoux test was positive in 26/42 patients. Acid Fast Bacilli (AFB) stain was
      positive in 1/25 while culture was positive in 7/25 specimens. There was
      1(14.28%) case of MDR tuberculosis. Most of the patients (95.45%), were diagnosed
      on positive histopathology report of involved tissues showing chronic
      granulomatous reaction with caseous necrosis.

PMID- 23866491
TI  - Omphalocoele, ten years experience at a tertiary care hospital.
AB  - Omphalocoele is a rare congenital anterior abdominal wall defect. We present 12
      cases of Omphalocoele seen in our hospital. Further, we have discussed the
      clinical presentation, antenatal diagnosis, associated abnormalities and final
      outcome of the cases.

PMID- 23866492
TI  - 'Community treatment order'--how often is it being used?

PMID- 23866493
TI  - Can telemedicine improve stroke outcomes?

PMID- 23866494
TI  - Ethical review in Pakistan: the credibility gap.
AB  - The concept of mandatory ethical review of research involving human participants
      is gradually taking root in Pakistani institutions. Based on the opinions of
      Institutional Review Board (IRB) members from institutions across the country,
      the process faces several challenges which threaten its integrity. The lack of
      registration or accreditation for IRBs has resulted in a wide variation in the
      calibre and working of such Boards. Despite the recent growth in numbers of
      people with formal bioethics degrees in the country, a majority of membership
      remains without any formal training for the work expected from them in ethical
      review. External pressures to influence deliberations, conflict of interest
      issues within board leadership and inconsistent application of review
      requirements all contribute in undermining the reliability of the process. Some
      of the most significant threats to independent and uninfluenced functioning of
      such boards arise from institutional leadership itself. In the opinions of IRB
      members, the review process has to be uniform, consistent and trustworthy if it
      is to gain the respect of researchers, and IRB need to be given the autonomous
      space to make independent decisions. Otherwise there is a real danger of IRBs
      being relegated to being no more than rubber stamping committees.

PMID- 23866495
TI  - Anticonvulsants, dermal complications.

PMID- 23866496
TI  - Vertebral arteries, efficacy of colour Doppler sonography in old people.

PMID- 23866497
TI  - Weighing scales in hospitals: how accurate are they? An observational study.

PMID- 23866498
TI  - Awareness of cardiopulmonary resuscitation in medical-students and doctors in
      Rawalpindi-Islamabad, Pakistan.
AB  - OBJECTIVE: To assess the level of awareness regarding basic and practical
      knowledge of cardiopulmonary resuscitation and its importance in the eyes of
      medical/dental students and doctors. METHODS: The cross-sectional study was
      conducted in medical and dental colleges as well as hospitals of Rawalpindi and
      Islamabad, Pakistan, from June to September 2011. Non-probability convenience
      sampling was used and structured questionnaires on basic and practical knowledge
      of the procedure were distributed. The questionnaire had 26 items related to
      basic and advanced knowledge of the required skills. Doctors were divided into
      two groups based on their years of service and practice. Those with less than 5
      years' experience were grouped as junior doctors, while rest as senior doctors.
      Descriptive statistics were employed to analyse the data using SPPS version 17
      and Microsoft Excel. Percentages were worked out and the results were
      interpreted. RESULT: Of the 1000 questionnaires distributed, 646 (64.6%) were
      received duly filled and represented the study sample. Of the 646 participants,
      34 (5.26%) were dentists, 424 (65.63%) were medical students, 92 (14.24%) were
      doctors and 96 (14.86%) were dental students. Basic knowledge of doctors was
      found to be better than that of dentists (n = 96; 50% vs. n = 8; 23%). Similarly,
      the advance knowledge of doctors was better than the dentists (n = 53; 58% vs. n
      = 11; 31%). The basic knowledge of junior doctors was found to be almost equal to
      the senior doctors (n = 26; 44.75% vs. n = 15; 45.5%). The advance knowledge of
      junior doctors was found to be better than the senior doctors (n = 27; 45.37% vs.
      n = 10; 29.48%). Among the students, 157 (37%) of the medical students had basic
      knowledge of CPR, while 36 (38%) dental students had basic knowledge of the
      topic. Medical students had more advanced knowledge (n = 157; 37%) than dental
      students (n = 34; 35%). CONCLUSION: The awareness of basic and advance knowledge
      of cardiopulmonary resuscitation skills in medical/dental students and doctors in
      Rawalpindi and Islamabad was inadequate.

PMID- 23866499
TI  - The polio bomb: what must Pakistan do?

PMID- 23866500
TI  - Problems faced in the public sector emergency rooms of Karachi.

PMID- 23866501
TI  - Relationship between blood groups and ulcers: revisiting the pioneer work.

PMID- 23866502
TI  - Current trends: management of esophageal varices.

PMID- 23866503
TI  - Medical system: a comprehensive comparison by medical students.

PMID- 23866504
TI  - Clinical audit: time to mandate.

PMID- 23866505
TI  - Unintentional, paediatric domestic injury in a semi rural area of Karachi.
AB  - OBJECTIVE: To identify the characteristics of unintentional domestic injury in
      children living in a semi-rural area of Karachi. METHODS: This retrospective
      descriptive study was carried out at a private hospital located at the northern
      outskirts of Karachi, Pakistan, from January 2005 to January 2007. We enrolled
      271 out-patient children of either gender with a positive injury history. A
      questionnaire inquiring socio-demographic characteristics, timing of injury,
      monthly variation, injury pattern and factors was filled out. Descriptive
      analysis and Chi-square test were applied to find out the statistically
      significant differences. RESULTS: Among the 271 patients, the male-to-female
      ratio was 1.2:1. Fall from height 145 (54%) or at the same level 52 (19%) was the
      commonest form of domestic unintentional injury across all ages. Children younger
      than 2 years of age, 140 (52%), were more prone to injuries, with 49 (51%) having
      fallen from the lap. Cuts with sharp domestic utensils were noted in 19 (6%),
      while 15 (6%) had burns. Submersion in underwater tank was noted in 20 (7%) cases
      and poisoning in 7 (3%). Majority of the injured children were from the low socio
      economic stratum and more injuries, 194 (72%), were reported during the summer
      months. CONCLUSION: Male children are more prone to suffer unintentional domestic
      injuries especially during summer vacations. Fall was the commonest pattern
      noted.

PMID- 23866506
TI  - Relationship of the angiographic extent of peripheral arterial disease with
      coronary artery involvement.
AB  - OBJECTIVE: To determine the co-incidence of coronary artery disease (CAD) in
      patients investigated for peripheral arterial disease (PAD), and to establish the
      relationship between the risk factors in the two groups of patients. METHODS: The
      prospective study, done from January 2005 and April 2009, at the Cardiology
      Clinic of Rize Education and Research Hospital, Rize and John F. Kennedy
      Hospital, Istanbul, Turkey, had a cohort of 307 patients who had been diagnosed
      with peripheral artery disease either clinically or by ultrasonography for the
      arteries of the lower extremities and had undergone coronary angiography and
      peripheral angiography in the same or different sessions. The patients were
      evaluated in terms of age, gender and atherosclerotic risk factors. Relationship
      of the extent of peripheral arterial disease with coronary artery involvement was
      investigated. RESULTS: Of the 307 patients, 251 (81.8%) were male, and the mean
      age was 62.1 +/- 9.5 years. In the study population, 178 (58.0%) patients were
      diagnosed as hypertensive, 84 (27.4%) patients were diabetic, 18 (5.9%) patients
      had a family history of coronary artery disease, 111 (36.2%) were smokers, 149
      (48.5%) were hypercholesterolemic, and 20 (6.5%) had cerebrovascular/carotid
      disease. In 92.3% of patients with peripheral arterial disease, various levels of
      coronary stenosis (P = 0.007) was noticed. Hypertension was a risk factor for
      both coronary and peripheral artery diseases (p = 0.012 and 0.027, respectively).
      Univariate logistic regression analysis demonstrated that the presence of
      peripheral artery disease was related to the coronary variety (Odds ratio [OR]:
      6, 95% CI: 1.4-25.5, P = 0.016) and severe cases (diffused atherosclerotic
      stenosis and complete occlusion in all segments) significantly indicated the
      presence of some coronary pathology (OR: 8, 95% CI: 1.7-37.4, P = 0.008). This
      relationship maintained its significance after adjustment for age, gender,
      hypercholesterolaemia, smoking, hypertension, diabetes, family history, and the
      presence of cerebrovascular/carotid disease (p = 0.010). CONCLUSIONS: Peripheral
      coronary artery diseases had similar risk factors. The extent of peripheral
      arterial disease observed during peripheral lower extremity angiography was
      significantly associated with the presence and severity of coronary artery
      disease. Particular attention should be focused on the possibility of coronary
      artery disease in patients with established and extensive peripheral arterial
      disease. Non-invasive, as well as invasive tests, should be performed to decrease
      morbidity and mortality risk of such patients.

PMID- 23866507
TI  - Electrophysciological analysis of entrapment neuropathies developed in acute and
      subacute period in paretic and non-paretic extremities in patients with stroke.
AB  - OBJECTIVE: To investigate entrapment neuropathies in stroke patients in a
      hospital in Turkey with Medical Research Council (MRC) score < or = 2/5 and in
      those with MRC score > or = 3/5. METHODS: The study comprising 40 patients from
      January 2008 to June 2009 in the Stroke Unit of the Department of Neurology,
      Yuzuncu Yil University in Van, Turkey, entailed electrophysiological analysis of
      median, ulnar, radial nerves, peroneal, tibial and sural nerves in paretic and
      nonparetic upper and lower extremities. National Institute of Health Stroke scale
      was used for the evaluation of neurological deficient, while nerve conduction
      studies were performed for the diagnosis of entrapment neuropathies (EN). The
      patients were divided into two groups based on their initial Medical Research
      Council (MRC) score: < 2/5 and > 3/5. Both groups had 20 patients each. The
      readings were compared in the control phase 45 to 50 days after the stroke.
      Paired samples test and t-test using SPSS version 15 were used for statistical
      analysis. RESULTS: Carpal tunnel syndrome (CTS) at wrist was found in 7 (35%)
      patients, cubital tunnel syndrome at elbow in 3 (15%) patients, and evident
      reduction in motor action potential values of peroneal, median and ulnar nerve in
      10 (50%) patients in the control studies for conduction on our patients with
      Medical Research Council (MRC) score of < or = 2/5, unlike the initial findings,
      in the paretic side. Among the patients, in the other group, 2 (10%) developed
      bilateral Carpel tunnel syndrome, and it was also detected in the healthy upper
      extremities in 2 (10%) more patients. In the control studies for conduction in
      patients with Medical Research Council score of 3/5, Carpel tunnel syndrome was
      detected in the healthy side in 4 (20%) patients and in the affected side in 3
      (15%) patients. CONCLUSION: In patients with severe paresis, if the affected
      extremity is not functional, symptoms of entrapment neuropathy are easy to occur.

PMID- 23866508
TI  - Atypical pathogens causing community-acquired pneumonia in adults.
AB  - OBJECTIVE: To determine the frequency of community-acquired respiratory pathogens
      with special focus on atypical organisms in patients presenting to a tertiary
      care facility with community-acquired pneumonia (CAP). METHODS: The descriptive
      study on adult patients was conducted from February 2007 to March 2008 at the Aga
      Khan University Hospital, Karachi. It comprised 124 consenting patients of age 16
      and above who presentd with a diagnosis of community-acquired pneumonia. The
      diagnostic modalities used were based on significant changes in antibody titer or
      persisting high antibody titers in the case of Mycoplasma pneumoniae and
      Chalmydia pneumoniae infections, or bacterial antigen in urine, in the case of
      Legionella pneumophila serogroup 1 infection. Pyogenic bacteria were identified
      on the results of respiratory secretions or blood cultures. Continuous data and
      categorical variables were worked out using SPSS version 15. RESULTS: Among the
      124 patients enrolled, an etiologic agent was identified in 44 (35.4%) patients.
      The most common organism was Mycoplasma pneumoniae (n = 21, 17%), followed by
      Chlamydia pneumoniae (n = 15, 12%), Streptococcus pneumoniae (n = 9, 7%),
      Haemophilus influenzae (n = 2, 1.6%), Klebsiella pneumoniae (n = 2, 1.6%) and
      Staphylococcus aureus (n = 1, 0.8%). Streptococcus pneumoniae was the most common
      organism isolated from blood cultures. No cases of Legionella pneumophila
      serogroup 1 were identified. CONCLUSIONS: Mycoplasma pneumoniae and Chalmydia
      pneumoniae are significant etiologic agents for community-acquired pneumonia
      occurring in Karachi. Local treatment guidelines for community-acquired pneumonia
      should include therapy directed specifically at these agents.

PMID- 23866509
TI  - Posterior reversible encephalopathy syndrome.
AB  - OBJECTIVE: To evaluate the Magnetic Resonauce Imaging (MRI) features in patients
      having Posterior Reversible Encephalopathy Syndrome. METHODS: This is a
      retrospective study from 8th June 2005 to 26th July 2009. Twelve patients were
      included who were confirmed to have Posterior Reversible Encephalopathy Syndrome,
      per imaging and clinical follow-up. Two neuro-radiologists blinded to the
      clinical condition retrospectively reviewed each image. Standard sequences were
      unenhanced Fluid Attenuated Inversion Recovery (FLAIR), T1-weighted, T2- weighted
      images followed by diffusion-weighted imaging and contrast-enhanced T1-weighted
      imaging. The regions involved were recorded on the basis of these sequences.
      RESULTS: Abnormal T2-weighted hyperintense signals (indicating vasogenic oedema)
      were consistently present in the parietal or occipital regions in 5 (41.6%), but
      other locations were also involved, including the deep white matter in 3 (25%),
      frontal lobes in 1, inferior temporal lobes in 1, cerebellar hemispheres in 1,
      and basal ganglia in 1 (8.3% each). On follow-up examination after 5-7 weeks, the
      patients showed marked improvement clinically and on neuro-imaging, and were
      discharged in a stable condition. After administration of gadolinium contrast,
      there was no area of abnormal enhancement in 11 cases and minimal enhancement was
      seen in 1 case. In our series, 3 patients had follow-up MRI examination which
      revealed the resolution of previously seen changes as well as the resolution of
      clinical symptoms. However, the diagnosis of Posterior Reversible Encephalopathy
      Syndrome was established in 9 other patients by resolution of clinical symptoms
      alone in 2-3 weeks. CONCLUSION: Awareness of diverse clinical and radiographic
      presentation of acute Posterior Reversible Encephalopathy Syndrome is essential
      to avoid misdiagnosis and treatment delay. Moreover, the syndrome is reversible
      with prompt treatment and has good outcome. This case series confirmed clinical
      improvement and recovery in most patients within weeks.

PMID- 23866510
TI  - Bone marrow examination of pancytopenic children.
AB  - OBJECTIVE: To assess the clinical profiles and determine the frequency of
      different aetiologies of pancytopenia based on bone marrow examination. METHODS:
      This is a retrospective study conducted over a 15 month period and included 279
      pancytopenic children of both sexes from 1 month to 16 years of age, who
      underwent bone marrow biopsy. Patients on cancer therapy or on immunosuppressive
      treatment and already diagnosed cases of aplastic anaemia were not included in
      the study. Clinical profiles and bone marrow morphology findings of the patients
      were reviewed. RESULTS: Acute leukaemia was the commonest aetiology 32.2%
      followed by Aplastic anaemia 30.8%, Megaloblastic anaemia 13.2% and miscellaneous
      aetiologies. Clinical presentation being pallor (81%), fever (68%), petechial
      haemorrhages (51%) bleeding manifestations (21.5%) and other features included
      hepatomegaly (44.8%), splenomegaly (37.2%) and lymphadenopathy (22.5%).
      CONCLUSION: Attempts should be made to establish the aetiology of pancytopenia
      without delay. Easily treatable causes if identified early can have a positive
      impact on mortality and morbidity of pancytopenic children.

PMID- 23866511
TI  - Does entry test make any difference on the future performance of medical
      students?
AB  - OBJECTIVE: To observe the influence/efficiency of entry test in the selection of
      students for MBBS. To see the effect of FSC and Entry test marks on the future
      performance of students in the coming years. METHODS: This was an Analytical
      Prospective Longitudinal study carried out in a private medical college from
      December 2009 to April 2011. Sampling was universal as all the students of year
      2009 who succeeded in getting admission were included. The subjects were selected
      at the time of admission and the whole class (admission intake) comprising of 100
      students during the admission year 2009 were studied. The same cohort was
      observed over a period of three years. The base line data was collected from the
      record, documents submitted at the time of admission and verified from the
      original record. RESULTS: The results of FSC and entry test are consistent in
      approximately all the percentage groups who got above 70% marks in FSC.
      Consistency was only disturbed in students who acquired 61-70% marks in FSC and
      entry test. The students who got 81-90% in FSC and Entry test performed well in
      first and second year MBBS. The males who had 66-70% marks in FSC were the poor
      performers (100% failed 5 out of 5) while among the females (33% failed) who got
      71-75% in FSC. Best performance was shown by those who got 81-85% in FSC i.e. 91%
      males and 90% females passed in annual examinations. The results of FSC and Entry
      test are highly significant in statistical application and hence there was no
      association between the entry test marks and future performance. CONCLUSION: FSC
      marks are of prime importance, and are the best marker for merit admission in
      medical college. Entry test is the tool for equalization in between different
      institutions, boards and provinces. It controls the errors and omissions done
      deliberately or unintentionally by students, board mal-practitioners and other
      confounders at institution and board level in FSC.

PMID- 23866512
TI  - Preferences of Iranian patients about style of labelling and calling of their
      physicians.
AB  - OBJECTIVE: To document the performance of patients regarding label styles of
      their doctors and modes of addressing them. METHODS: In this descriptive survey,
      400 patients, at two teaching hospitals--Hajar and Kashani--with a mean age of
      40.5 +/- 19.5 years were enrolled. Their demographic data, disorder type and
      duration were recorded. Photos demonstrating different label and attire styles
      based on Iranian culture were shown to the patients and they were asked to mark
      their performances about the necessity of wearing name badge. They were also
      requested to nominate the way they preferred to be addressed by the doctors.
      RESULTS: Of the participants, 180 (45%) were men; 307 (76.8%) were married; and
      the mean duration of hospitalisation was 2.5 +/- 2.1 days. Most of the patients,
      (n = 320; 80%) stated that the doctor should always wear a name badge; 301
      (75.3%) preferred to call their physicians by title; and 227 (56.8%) preferred to
      be called by their surnames. Patients preferred to have female physicians wearing
      white coat, shirt and trousers as the preferred dress code. CONCLUSION: Patients
      in the study preferred to have the physicians professionally attired, with the
      only difference being the dark veil for female physicians. Name badge and white
      coat were also preferred by the patients.

PMID- 23866513
TI  - Dyspepsia prevalence in general population aged over 20 in the west part of Iran.
AB  - OBJECTIVE: To estimate the prevalence of dyspepsia in the general population aged
      over 20 in western Iran. METHODS: The cross-sectional study was conducted among
      the randomly selected general population over the age of 20 years in Sanandaj
      city. Iran, from April to December 2009. A questionnaire containing demographic,
      symptoms and history variables was used. Dependent variables were self-reported
      gastrointestinal symptoms. The prevalence of dyspepsia in different groups was
      analysed using chi square test, while logistic regression analysis was done to
      determine dyspepsia, ulcer-like, dysmotility-like and reflux-like prevalence
      after controlling the confounders. RESULTS: Among 590 respondents, the prevalence
      of dyspepsia was 54.6% (n = 322). Among them were 243 (41.2%) cases of
      uninvestigated dyspepsia. According to dyspepsia classification, the prevalence
      of ulcer-like, dysmotility-like, reflux-like and non-specific dyspepsia were
      31.5% (n = 186), 11% (n = 65), 27.3% (n = 161) and 12.4% (n = 74), respectively.
      Difference in dyspepsia prevalence between men and women persisted after
      adjustment for other factors (p =0.01) and dyspepsia prevalence was higher in
      over-60-years old group than the middle aged group (p = 0.008). CONCLUSIONn: The
      study showed high prevalence of dyspepsia in the general population. Gender, age,
      family history and theophylline consumption affect the prevalence of dyspepsia.

PMID- 23866514
TI  - Efficacy of rivastigmine in comparison to ginkgo for treating Alzheimer's
      dementia.
AB  - OBJECTIVES: To assess the efficacy of the Ginkgo biloba in patients with dementia
      of the Alzheimer type in slowing down the disease's degenerative progression and
      the patients' cognitive impairment compared with rivastigmine. METHODS: Total 56
      patients aged 50-75 years, suffering from dementia, were allocated into one of
      the two treatments: group 1) Ginkgo biloba (120 mg daily dose); group 2)
      rivastigmine (4.5 mg daily dose) in a 24-week randomized double blind study. The
      degree of severity of dementia was assessed by the Seven Minute test and the Mini
      Mental State Examination. RESULTS: Our results confirm the clinical efficacy of
      rivastigmine in the dementia of the Alzheimer type, comparing to Ginkgo biloba.
      There are few published trials that have directly compared a cholinesterase
      inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase
      inhibitor with Ginkgo biloba for dementia of the Alzheimer type. CONCLUSION: Our
      study suggests that there are differences in the efficacy of Ginkgo biloba and
      rivastigmine in the treatment of Alzheimer's dementia. In addition, this study
      suggested that cholinesterase inhibitors should be used in preference to Ginkgo
      biloba in patients with mild to moderate AD.

PMID- 23866515
TI  - Tissue plasminogen activator and plasminogen activator inhibitor-1 levels in
      patients with acute myocardial infarction and unstable angina.
AB  - OBJECTIVE: To compare levels of tissue plasminogen activator and plasminogen
      activator inhibitor-1 levels in patients with acute myocardial infarction and
      unstable angina in order to understand the use of high sensitivity C-reactive
      protein (hsCRP), coagulation and fibrinolysis markers for cardiovascular risk
      assessment. METHODS: The cross-sectional case-control study compared circulating
      concentrations of high sensitivity C reactive protein (hsCRP), fibrinogen, tissue
      type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1)
      between patients of acute myocardial infarction (AMI) (n = 67), Unstable Angina
      Pectoris (UA) (n = 35) and healthy control subjects (n = 39) at the King Khalid
      University Hospital, Riyadh, Saudi Arabia, from June 2006 to August 2007.
      RESULTS: The patients had significantly higher hsCRP (1.06 +/- 0.11 vs 0.52 +/-
      0.14, p < 0.01), fibrinogen (426.21 +/- 24.09 vs 329.32 +/- 13.93, p < 0.05), PAL
      1 (44.02 +/- 6.05 vs 19.35 +/- 3.94, p < 0.01) and tPA (12.31 +/- 1.16 vs 9.49 +/
      0.86, p < 0.05) compared to the controls. Fibrinogen (329.32 +/- 13.93) and PAL
      1 (19.35 +/- 3.94) were higher in both angina and infarction groups compared to
      the healthy subjects (p < 0.01). Between the two categories of patients the
      difference between Fibrinogen (449.60 +/- 52.98 vs 419.46 +/- 23.42) and PAL-1
      (52.00 +/- 17.34 vs 43.19 +/- 6.10) levels were non-significant. Also, the
      difference in tPA levels between the controls and angina patients was
      nonsignificant (9.49 +/- 0.86 vs 9.91 +/- 1.24 p > 0.05). It was higher in
      infarction patients (14.79 +/- 3.14) compared to angina patients and the
      controls, (p < 0.05). Compared to the controls, hsCRP levels were significantly
      higher in both the patient groups (0.52 +/- 0.14, 1.05 +/- 0.28, 1.40 +/- 0.20, p
      < 0.01). Moreover, they were significantly higher in infarction patients than
      those suffering from angina (p < 0.05). CONCLUSIONS: CAD patients had a
      procoagulant state and presented with higher levels of hsCRP compared to the
      healthy individuals. Moreover, there were significant differences in coagulation
      markers and hsCRP between angina and infarction patients.

PMID- 23866516
TI  - Impact of probability estimation on frequency of urine culture requests in
      ambulatory settings.
AB  - OBJECTIVE: To determine the perceptions of the medical community about urine
      culture in diagnosing urinary tract infections. METHODS: The cross-sectional
      survey based of consecutive sampling was conducted at Shifa International
      Hospital, Islamabad, on 200 doctors, including medical students of the Shifa
      College of Medicine, from April to October 2010. A questionnaire with three
      common clinical scenarios of low, intermediate and high pre-test probability for
      urinary tract infection was used to assess the behaviour of the respondents to
      make a decision for urine culture test. The differences between the reference
      estimates and the respondents' estimates of pre- and post-test probability were
      assessed. The association of estimated probabilities with the number of tests
      ordered was also evaluated. The respondents were also asked about the cost
      effectiveness and safety of urine culture and sensitivity. Data was analysed
      using SPSS version 15. RESULTS: In low pre-test probability settings, the disease
      probability was over-estimated, suggesting the participants' inability to rule
      out the disease. The post-test probabilities were, however, under-estimated by
      the doctors as compared to the students. In intermediate and high pre-test
      probability settings, both over- and underestimation of probabilities were
      noticed. Doctors were more likely to consider ordering the test as the disease
      probability increased. Most of the respondents were of the opinion that urine
      culture was a cost-effective test and there was no associated potential harm.
      CONCLUSIONS: The wide variation in the clinical use of urine culture necessitates
      the formulation of appropriate guidelines for the diagnostic use of urine
      culture, and application of Bayesian probabilistic thinking to real clinical
      situations.

PMID- 23866517
TI  - Awareness and ethical views regarding life support among doctors working in
      tertiary care facilities of Karachi, Pakistan.
AB  - OBJECTIVE: To assess the knowledge of Life Support (LS) among doctors and to
      determine their ethical beliefs for the continuation or termination of Basic and
      Advanced Life Support services. METHODS: This cross-sectional study was done from
      March to June 2009 that involved 110 doctors of three teaching Hospitals in
      Karachi (Jinnah Postgraduate Medical Centre, Aga Khan University and Ziauddin
      University hospitals). All the subjects were selected by random sampling and were
      then analysed on the basis of self-administered questionnaires. RESULTS: Out of
      the 110 doctors who took the survey, 109 (99%) had heard of Life Support. In the
      breakdown of doctors, 1 out of the 18 consultants (5.6%), 5 of 45 PGs (11%) and 2
      out of 47 House Officers (4%) who took part in this study were unable to
      correctly identify the right definition of LS. Out of the total number (n = 110)
      of doctors, 94 (85%) said they would use Life Support in their patients and 41
      (43%) of them thought life support was the only way the doctor can "do what he is
      supposed to do i.e. save a life", while the other reason for using LS was
      "Religiously, the right way". CONCLUSION: LS is still a highly sensitive subject
      that needs still more awareness in Karachi, Pakistan. It was surprising to find
      out that the knowledge of LS by residents, postgraduates and even consultants was
      not as high as expected. Making Basic Life Support as a part of the undergraduate
      course might help in clarifying the discrepancies present in the knowledge of
      Life Support.

PMID- 23866518
TI  - Primiparity as an intrapartum obstetric risk factor.
AB  - OBJECTIVE: To ascertain whether primiparity is an intrapartum obstetric risk
      factor for maternal and perinatal outcome. METHODS: The comparative case
      controlled study was conducted at the Department of Obstetrics and Gynaecology of
      Sir Syed Hospital, a tertiary care facility in Karachi, from January 2008 to June
      2009. A self-developed structured proforma was used to obtain relevant
      information about 400 women who were recruited part of the study: 200
      primigravida and 200 multigravida. The proforma covered detailed record of labour
      management. Inclusion criteria was singleton pregnancy with cephalic presentation
      at term. Exclusion criteria was significant medical illness, recurrent
      miscarriages, bad obstetrical history, intrauterine death, congenital anomalies,
      previous uterine scar, multiple pregnancy, malpresentation, significant
      antepartum haemorrhage and Rhesus (Rh) incompatibility. RESULTS: Primigravidas
      were at significantly higher risk for prolonged first and prolonged second stage
      of labour, increased chances of foetal distress during labour and need for
      intensive monitoring as compared to the multigravidas. Primigravidas were also at
      significantly increased risk for operative vaginal delivery and emergency
      caesarean section. The chances of primary postpartum haemorrhage in primigravidas
      were found to be more, and perinatal morbidity was also increased in the group.
      CONCLUSION: Results highlighted primiparity as a risk factor for maternal and
      perintal outcome in comparison with multigravida.

PMID- 23866519
TI  - Predictors of initiation, continuation and transition of drug use in south
      eastern Iran.
AB  - OBJECTIVES: To identify factors associated with the initiation continuation,
      transition and cessation of substance abuse in Zahedan, Iran. METHODS: The
      retrospective study reviewed the profile of 536 addicts admitted to both public
      and private outpatient treatment centres in the study area. For each individual,
      data were collected on sociodemographic characteristics, initiation and patterns
      of drug abuse and any changes in the patterns. To analyze the data, Kruskal
      Wallis, Chi-square, Log-rank test, Logistic regression and Cox proportional
      hazards models were used. RESULTS: The median age of the first drug abuse was 20
      (95% CI: 19.7 - 20.3) years with significant heterogeneity by gender and marital
      status (p < 0.001). The age of the first drug use and maritaI status were
      significant factors for the continuation of drug use (p < 0.001). The study also
      indicated that male gender, single life, low level of education, early onset of
      substance use and type of first used drug act as facilitators for transition to
      new drugs (p < 0.05). Besides, the present study revealed the significant effect
      of marital status, education and type of first used drug on personal decisions
      towards drug use cessation (p < 0.05). CONCLUSION: A number of predictive factors
      of substance abuse identified in the study are of utmost important for any
      preventive effort.

PMID- 23866520
TI  - Abdominal tuberculosis: epidemiologic profile and management experience of 233
      cases.
AB  - OBJECTIVE: To document the epidemiologic profile and management outcome of
      patients with abdominal tuberculosis in a tertiary care setup. METHODS: This
      descriptive case series was conducted at the Department of Surgery, Pakistan
      Institute of Medical Sciences (PIMS), Islamabad, between January 2003 and
      December 2008. All adult patients of either gender who presented with abdominal
      tuberculosis and were managed at our hospital during the study period were
      included in the study on the basis of convenience sampling. Numerical data were
      expressed as mean +/- standard deviation, while categorical data were analysed
      using SPSS version 10. Chi square test was conducted to compare categorical
      variables. RESULTS: Of the 233 adult patients with abdominal tuberculosis who
      were part of the study, 110 (47.21%) were males and 123 (52.78%) females. The
      mean age was 28.21 +/- 5.75 years. Majority of our patients (80.68%) belonged to
      poor families. History of concomitant pulmonary tuberculosis was found in 23
      (9.87%) patients. Family history of tuberculosis was found in 13 (5.57%)
      patients. Of the patients 157 (67.38%) presented with acute abdomen; strictures
      were the most common operative finding (n = 161; 69%); the patients needing
      hospitalisation were 204 (87.55%), with the mean hospital stay being 19.55 +/-
      4.51 days. The in-hospital mortality was 5 (2.14%). CONCLUSION: Abdominal
      tuberculosis was found prevalent in the population and predominantly affected the
      younger lot belonging to the poor socioeconomic strata. Majority of the cases
      were of primary intestinal variety, and in a small proportion it was secondary to
      pulmonary tuberculosis. Majority of the patients presented with complications
      such as acute intestinal obstruction, intestinal perforation and peritonitis,
      necessitating emergency laparotomy.

PMID- 23866521
TI  - Awareness and attitude towards sex health education and sexual health services
      among youngsters in rural and urban settings of Sindh, Pakistan.
AB  - OBJECTIVES: To assess attitudes and awareness regarding sexual health education
      and services among young individuals in Pakistan. METHODS: A cross-sectional
      survey was conducted in urban and semi-urban districts of Sindh, Pakistan, in
      2010. A self-administered questionnaire was distributed in-hand among 200 young
      people aged 16-25 years; who were selected on the basis of convenience sampling.
      Of the questionnaires distributed, 165 (82%) were returned. After checking for
      quality and consistency, 150 (75%) forms were found good enough to be used for
      categorical analysis, using PASW Statistics 18 for Mac 2008 version. RESULTS: Of
      the 150 participants, 94 (63%) were males and 56 (37%) were females. A quarter of
      them (n = 38; 25.3%) said sexual health services were available too far away from
      their area. Besides, they also found the staff to be 'not competent.' Almost one
      third (n = 49; 32.7%) reported of not having matching gender choice (male or
      female) of professionals with whom they could feel comfortable sharing their
      sexual health concerns. Majority of the participants (n = 101; 67.3%) considered
      trained health professionals as the primary source of sexual health education,
      whereas, 90 (60%), 75 (50%), and 59 (39.3%) also reported to have secondary
      sources, including internet, parents and telephone helpline respectively.
      CONCLUSION: Sexual health education and services for the young are barely enough
      or satisfactory in terms of quantity and quality in Pakistan, suggesting a case
      for having curriculum-based sex education implemented in academic institutions.

PMID- 23866522
TI  - Different approaches to acute organophosphorus poison treatment.
AB  - Organophosphorus compounds (OPCs) have a wide variety of applications and are a
      serious threat for self-poisoning, unintentional misuse, terrorist attack,
      occupational hazard and warfare attack. The present standard treatment has been
      reported to be unsatisfactory. Many novel approaches are being used and tested
      for acute organophosphorus (OP) poison treatment. The bioscavenger concept
      captured high attention among the scientific community during the last few
      decades. Other approaches like alkalinisation of blood plasma/serum and use of
      weak inhibitors against strong inhibitors, though it showed promising results,
      did not get such wide attention. The introduction of a novel broad-spectrum oxime
      has also been in focus. In this mini-review, an update of the overview of four
      different approaches has been discussed. The standard therapy that is
      atropine+oxime+benzodiazepine along with supportive measures will continue to be
      the best option with only the replacement of a single oxime to improve its broad
      spectrum efficacy.

PMID- 23866523
TI  - Chemotherapy-induced neutropenic necrotizing enterocolitis: a review.
AB  - Neutropenia is a common toxicity of systemic cytotoxic therapy. Neutropenic
      enterocolitis (NE) is a rare occurrence but can be fatal, subsequent to
      neutropenia. The exact incidence and frequency is difficult to establish, but is
      usually underestimated. It is often missed but has recently been appreciated with
      increasing frequency in solid tumours. NE was initially reported with taxenes but
      now an increasing number of chemotherapeutic drugs are implicated. NE incidence
      is expected to increase with the use of dose dense regimens, myeloablative
      cytotoxic protocols, tissue transplants, and emerging newer molecules. The usual
      presentation is often non-specific and often over shadowed by the symptomatology
      of primary malignant disease and toxicity symptoms of chemotherapy. The basis of
      diagnosis is clinical, radiological (ultra sound/CT scan), per operative
      findings, and eventually post mortem. Treatment options of this highly fatal
      phenomenon varies from conservative to early surgical intervention. NE is
      expected to be diagnosed with increasing frequency. The factors leading to it are
      mucosal injury, caecal distension with resultant ischaemia, cytotoxic drugs, and
      microbiological agents. A high index of clinical suspicion and an early diagnosis
      is paramount for better outcome. Irrespective of management employed,
      conservative or upfront surgical intervention, it has a poor out come with high
      mortality. A clinical suspicion, early diagnosis, and prompt management are the
      key to a better result. There is need to identify people at high risk by
      prognostic factors, large scale studies, and formulating consensus management
      guidelines. At present individualized risk assessment based strategy is
      advocated.

PMID- 23866524
TI  - Xeroradiophotography.
AB  - Sensitive emulsion of current radiographic film is constructed by silver halogen
      crystals, including millions of ions that form the image. The resolution of image
      is associated with the number of ions, but they cannot exceed a certain limit in
      terms of surface area unit. Besides, relevant accessories and stages of
      processing also mean longer time and higher cost. To reduce such barriers, the
      Xeroradiophotography system was designed and built on the basis of Xero Physical
      phenomenon in which the image is formed by taking advantage of both Xrays and
      visible light. Besides, different physical method for developing and fixing is
      used, replacing the conventional photochemical process with the electrostatic
      function. As a result, high-quality images are obtained while reducing radiation
      and other biological hazards, making radiography safer and quicker and less
      expensive. As this paper highlights, the device could be best used for soft
      tissue procedures like mammography.

PMID- 23866525
TI  - Carotid cavernous fistula with bilateral thalamic infarct.
AB  - Carotid cavernous fistula (CCF) is an abnormal communication between cavernous
      sinus and carotid arterial system. Diagnosis depends on clinical manifestations
      and MRI findings and angiography. Clinical presentation of CCFs is characterized
      with chemosis, orbital bruit and pulsatile proptosis. Cranial nerve dysfunction
      and orbital pain might accompany these symptoms. Although spontaneous remission
      might occur, sometimes CCF might develop life threatening complications. Here in
      this case we presented a patient with CCF who afterwards developed bilateral
      thalamic infarct. Cerebral ischemia in CCF is a rare complication and CCF
      together with bilateral thalamic infarct has not been reported before.

PMID- 23866526
TI  - Familial presence of early onset Fuchs' corneal endothelial dystrophy, a report
      of two rare cases.
AB  - A 15-year-old girl presented to our clinic with a history of gradual loss of
      vision and photosensitivity. She had bilateral corneal haze with stromal oedema.
      Her best-corrected visual acuity was 20/400 in the right eye and 20/200 in the
      left. She underwent penetrating keratoplasty in both eyes. Corneal histopathology
      revealed a pattern similar to Fuchs' endothelial dystrophy. The graft settled
      well and stayed clear while the vision kept improving. Her brother also presented
      with similar symptoms.

PMID- 23866527
TI  - Coeliac disease and multiple immunodeficiencies: case report of a diagnostic
      dilemma.
AB  - Coeliac disease (CD) often coexists with other autoimmune and primary
      immunodeficiency diseases (PID), creating a problem in timely diagnosis and
      management. An unusual case of coeliac disease that was difficult to diagnose and
      manage because of its unusual clinical presentation. Initially diagnosed as
      celiac disease but showed poor response to standard therapy is reported. Frequent
      attacks of opportunistic infections led to immunodeficiency work-up that revealed
      natural killer cell (NK) deficiency with low serum IgA and IgG2 levels. The
      patient eventually succumbed to recurrent infections. The co-existence of PID is
      unusual in a patient with CD. This case report highlights the importance of
      investigating PID in patients with autoimmunity.

PMID- 23866528
TI  - Extranodal non-Hodgkin's lymphoma in HIV.
AB  - Lymphoma in acquired immunodeficiency syndrome (AIDS) is associated with frequent
      involvement of extra-nodal sites, rapid clinical progression and aggressive
      histology. We present a case of extra nodal non-Hodgkin's lymphoma (NHL) with
      probable multifocal involvement.

PMID- 23866529
TI  - Urinary tract infection presenting as jaundice in neonates.
AB  - Neonatal Hyperbilirubinaemia is a common finding during the first postnatal week.
      Physiological jaundice occurs in first week of life in 60% of term and 80% of
      premature neonates. Non physiologic or pathologic jaundice occurs in 5-10% of
      newborns which require intervention. According to AAP guidelines laboratory
      investigation for jaundice include total serum bilirubin, blood Type and coombs
      test and if the baby has an elevation of direct reacting or conjugated bilirubin,
      there should be a urine analysis and urine culture. Here we are presenting 5
      cases that developed indirect hyperbilirubinaemia and routine workup done
      according to AAP guidelines were normal. On extensive investigation all cases
      found to have urinary tract infection despite of having indirect bilirubin and
      they needed course of antibiotics according to sensitivities and follow up
      ultrasound. From our experience we suggest that UTI should be considered as a
      cause of neonatal jaundice especially when indirect bilirubin peaks after one
      week of life at mean age of 10.8 +/- 2.38 days.

PMID- 23866530
TI  - Gender selection: is there a growing trend?

PMID- 23866531
TI  - Long-term effect of carotid surgery in asymptomatic stenosis.

PMID- 23866532
TI  - Descriptive statistics--presenting your results I.

PMID- 23866533
TI  - Comments: Poor patient counseling: a black mark on our health care system.

PMID- 23866534
TI  - Short-term complications after bilateral internal mammary artery grafting--a
      retrospective study.
AB  - OBJECTIVES: To analyze our experience of conducting Bilateral Internal Mammary
      Artery (BIMA) grafting, using both pedicled and free grafts for coronary
      revascularization, assessing the safety and efficacy of the procedure and
      comparing any differences observed between the two techniques of harvesting the
      grafts. METHODS: A retrospective cross sectional study was conducted in July 2010
      in which all 48 patients undergoing bilateral internal mammary artery grafting
      for coronary bypass surgery at the Aga Khan University Hospital from 1996 to 2010
      were reviewed and evaluated. The main outcome measures were perioperative
      mortality and early morbidity with particular reference to cerebrovascular
      accidents, sternal wound complications and re-opening for bleeding. Chi-square
      test was used to elicit any meaningful associations between patient
      characteristics and post-operative outcomes. RESULTS: Of the 48 patients
      undergoing bilateral IMA grafting, 46 were males and 2 females. The mean age was
      48 +/- 9.4 years. Dyslipidaemia and smoking were the most common identifiable
      risk factors for coronary vascular disease. Following the 40 elective and 8
      emergent surgeries, there was one hospital death. The most common post-operative
      complications were arrhythmias and wound infection. Diabetes and obesity were not
      observed to be associated with an increased risk of developing surgical site
      infection. CONCLUSIONS: Our study suggests that the short-term efficacy and the
      safety profile of bilateral IMA grafting for coronary revascularization is
      clinically acceptable. Long-term follow-up studies should be done to assess the
      cardiac event-free survival of these individuals evaluating its applicability as
      a routine for coronary artery bypass grafting in Pakistan.

PMID- 23866535
TI  - [The articles invite reflection].

PMID- 23866536
TI  - [Drug report decries polypharmacy. Especially elderly patients receive too many
      different drugs].

PMID- 23866537
TI  - [Study: stigmatization psychiatric patients is on the rise. Biological
      explanatory models could be the cause].

PMID- 23866538
TI  - [Awareness of and changing subjective theories. Patient suicide in psychiatry:
      peer counseling helps nurses with personal adjustment].

PMID- 23866539
TI  - [Reflecting on nursing care. Violence in routine nursing - Pflegezeitschrift
      author Ulrich Kamphausen points out fateful interventions and behaviors].

PMID- 23866540
TI  - ["Make a happy face!" Depressions: etiology and therapeutic approaches].

PMID- 23866541
TI  - [Empathy will not help. Managing elderly depressed patients in geriatric
      nursing].

PMID- 23866542
TI  - [Behavior and well-being of people with dementia in a social care group.
      Observation study with dementia care mapping].
AB  - Social care groups for people with dementia areone way to relieve family
      caregivers and to activate individuals with dementia. This study aimed to
      describe one social care group and investigate the well-being of the groups
      members. The research question therefore was: What are people with dementia doing
      and how do they feel in a social care group? In this descriptive observation
      study we observed three group sessions in one social care group with five members
      in North Rhine-Westphalia (Germany) using Dementia Care Mapping (DCM). The
      results show that there was a special course of action fixed by meals, welcoming
      and farewell. The behaviour and well-being varied. Leisure like doing handicraft
      and interaction were depicted as main activities. The well-being was high, if
      participants had energetic activities and the course of action of the different
      group members was similar. Interestingly one person was excluded from almost all
      activities. It is important for staff to know the constellation of the group and
      to include all visitors.

PMID- 23866543
TI  - [Between opportunity and dead end career. Is a 3 year direct education in
      psychiatric nursing in the future? - A memorandum].

PMID- 23866544
TI  - [Properly documenting practical learning outcomes. Educational documentation in
      nursing careers].

PMID- 23866545
TI  - [Of asylum attendants and co-therapists].

PMID- 23866546
TI  - ["When the patients saw the nurses, they cried for help. Nursing cholera patients
      by Kaiserwerther deaconesses in Hamburg 1892"].

PMID- 23866547
TI  - [Psychoeducation for relatives of schizophrenia patients].

PMID- 23866548
TI  - [Mother house association reduce wage level. In focus: the compensation of nurses
      since the Kaiser era].

PMID- 23866549
TI  - [Vendors must give accurate information. Shopping on the internet].

PMID- 23866550
TI  - [Thrombocyte aggregation. Thromboses, blood coagulation and venous blood flow].

PMID- 23866551
TI  - [When the ground under the feet disappears ... Managing depression and addictive
      behavior in the elderly].

PMID- 23866552
TI  - ... to see or not see.

PMID- 23866553
TI  - Vertical size disparity and the correction of stereo correspondence.
AB  - We examined the stage of vertical-disparity processing that produces a global
      stereoscopic slant. In two psychophysical experiments, we measured perceived
      slant about a vertical axis for two-dimensional stereoscopic patterns consisting
      of random dots, concentric lines, and radial lines. Binocular image differences
      were introduced into each pattern by vertically magnifying either the entire
      image for the right eye or that for the left eye. Because the continuous lines
      were geometrically ambiguous in local stereo correspondence, the three patterns
      differed from each other in the local horizontal disparity measured in retinal
      coordinates. The two experiments revealed that, despite the differences in the
      retinal horizontal disparity, the slant settings were generally similar for the
      three patterns, in both short and long viewing distances (25 cm and 120 cm,
      respectively). These results are consistent with the idea that the visual system
      uses vertical disparity at least when establishing local stereo correspondence. A
      Bayesian model is proposed to account for the results.

PMID- 23866555
TI  - The Ouchi-Spillmann illusion revisited.
AB  - In a disk-ring pattern composed of horizontally oriented checks in the centre and
      vertically oriented checks in the surround, the centre appears to slide relative
      to the surround when the pattern is slowly moved about. This phenomenon has been
      called the Ouchi illusion. Slow sliding movements may represent involuntary
      ocular drifts, while occasional jerks suggest a contribution by microsaccades.
      The conditions under which the illusion occurs both with free viewing and in the
      absence of involuntary eye movements are reviewed. Illusory sliding is most
      pronounced with diagonal movement of the stimulus pattern, resulting in apparent
      motion orthogonal to the orientation of the disk. The illusion requires checks of
      low spatial frequency; it persists with low luminance contrast and blur of the
      inducing pattern, but is absent at equiluminance. These results suggest a
      magnocellular neuronal mechanism. Sliding continues to be seen with an empty
      annular zone separating centre and surround, and is seen even when there is no
      concentric surround at all, just two abutting flanks. Nine hypotheses proposed to
      account for the illusory motion of the centre relative to the surround are
      reviewed. Among these the models based on an integration bias of local motion
      vectors (Mather 2000 Perception 29 721-727) and Type II plaid motion (Ashida2002
      Vision Research 42 1413-1420) come closest to explaining illusory sliding in the
      Ouchi figure, but open questions remain. Specifically, more research is warranted
      to correlate the predicted with the perceived direction of sliding motion in both
      check and grating patterns.

PMID- 23866554
TI  - The effect of spectral filters on visual search in stroke patients.
AB  - Visual search impairment can occur following stroke. The utility of optimal
      spectral filters on visual search in stroke patients has not been considered to
      date. The present study measured the effect of optimal spectral filters on visual
      search response time and accuracy, using a task requiring serial processing. A
      stroke and control cohort undertook the task three times: (i) using an optimally
      selected spectral filter; (ii) the subjects were randomly assigned to two groups
      with group 1 using an optimal filter for two weeks, whereas group 2 used a grey
      filter for two weeks; (iii) the groups were crossed over with group 1 using a
      grey filter for a further two weeks and group 2 given an optimal filter, before
      undertaking the task for the final time. Initial use of an optimal spectral
      filter improved visual search response time but not error scores in the stroke
      cohort. Prolonged use of neither an optimal nor a grey filter improved response
      time or reduced error scores. In fact, response times increased with the filter,
      regardless of its type, for stroke and control subjects; this outcome may be due
      to contrast reduction or a reflection of task design, given that significant
      practice effects were noted.

PMID- 23866556
TI  - Recovering 3-D shape: roles of absolute and relative disparity, retinal size, and
      viewing distance as studied with reverse-perspective stimuli.
AB  - When viewing reverspective stimuli, data-driven signals such as disparity, motion
      parallax, etc, help to recover veridical three-dimensional (3-D) shape. They
      compete against schema-driven influences such as experience with perspective,
      foreshortening, and other pictorial cues that favor the perception of an illusory
      depth inversion. We used three scaled-size versions of a reverspective to study
      the roles of retinal size, binocular disparity, and viewing distance--that
      influences both vergence and accommodation--in recovering the true 3-D shape.
      Experiment 1 used three conditions, in each of which a parameter was kept fixed
      across the three stimulus sizes: (a) fixed retinal size, (b) fixed viewing
      distance, (c) fixed disparity. The predominance of the veridical percept was
      recorded. Generally, the illusion strength was the same when the viewing distance
      was fixed, despite significantly different disparities and retinal sizes;
      conversely, illusion strength changed significantly in fixed-disparity and fixed
      retinal-size conditions. Experiment 2 confirmed the results of experiment 1b
      (roughly equal performances for fixed viewing distance, independent of size) for
      two additional distances. Viewing distance and "scaled disparity" (disparity
      divided by retinal size) are good predictors of the data trends. We propose that
      disparity scaling is supported by both mathematical and 3-D shape considerations.

PMID- 23866557
TI  - Kinematic parameters that influence the aesthetic perception of beauty in
      contemporary dance.
AB  - Some experiments have stablished that certain kinematic parameters can influence
      the subjective aesthetic perception of the dance audience. Neave, McCarty,
      Freynik, Caplan, Honekopp, and Fink (2010, Biology Letters 7 221-224) reported
      eleven movement parameters in non-expert male dancers, showing a significant
      positive correlation with perceived dance quality. We aim to identify some of the
      kinematic parameters of expert dancers' movements that influence the subjective
      aesthetic perception of observers in relation to specific skills of contemporary
      dance. Four experienced contemporary dancers performed three repetitions of four
      dance-related motor skills. Motion was captured by a VICON-MX system. The
      resulting 48 animations were viewed by 108 observers. The observers judged beauty
      using a semantic differential. The data were then subjected to multiple factor
      analysis. The results suggested that there were strong associations between
      higher beauty scores and certain kinematic parameters, especially those related
      to amplitude of movement.

PMID- 23866558
TI  - Slant perception for stairs and screens: effects of sex and fatigue in a
      laboratory environment.
AB  - The apparent slope of a hill or staircase, termed geographical slant perception,
      is exaggerated in explicit awareness. Across two experiments this paper tests the
      use of a laboratory environment to study geographical slant perception. First,
      using a student-aged sample (N = 166), we examine the similarity of slant
      estimates in the field with those made in the laboratory using life-sized images
      of the built environment as stimuli. Results reveal no differences in slant
      estimates between the two test environments. Furthermore, three traditional
      measures of perceived geographical slant (verbal, visual, and haptic) appear
      sensitive to a difference in slant of only 3.4 degrees in both the field and
      laboratory environments. In a follow-up experiment we test the effect of fatigue
      on slant estimates in the laboratory. In line with previous research with outdoor
      stimuli, fatigued participants provided more exaggerated explicit reports of
      slant relative to those in a control group, and females gave more exaggerated
      slant estimates than males across both experiments. The current set of findings
      open the door to future studies of geographical slant perception that may be more
      suited to laboratory conditions.

PMID- 23866559
TI  - The influence of spatial and feature probability cuing in visual search.
AB  - Certain aspects of a visual search task, such as the location where a target
      often appears, are learned over time and can serve as a source of attentional
      guidance. An example ofthis implicit learning, spatial probability cuing speeds
      detection of targets that appear in probable locations. The current study
      investigated target feature probability learning and its relation to implicit
      spatial probability learning. Results reveal that individuals are sensitive to
      small changes in the spatial probability of targets, even incidentally learning
      moderate probabilities. However, feature-based probability differences impacted
      visual search times much less. Implications for these findings are discussed.

PMID- 23866560
TI  - A new method for assessing self-touch enhancement of the foot in stroke patients
      with mobility problems.
AB  - Patient NG is the first reported case of lower-limb 'self-touch enhancement'
      following stroke. Mobility problems prevented NG from reaching to touch her foot,
      thus we used a self-touch rubber-hand paradigm to mimic the conditions of self
      administered touch. With vision precluded, NG administered stimulation to a
      prosthetic limb while the Examiner administered synchronous stimulation to NG's
      affected left foot. NG detected all stimulation administered with our self-touch
      paradigm, whereas in the control condition (with NG not involved in administering
      stimulation), NG had failed to detect one-third of Examiner-administered
      stimulation. When mobility problems are a barrier to investigating self-touch
      enhancement, the self-touch paradigm can be used to demonstrate residual tactile
      sensation following stroke.

PMID- 23866561
TI  - Do performance measures help healthcare?

PMID- 23866562
TI  - Patient experience: Perception is everything.

PMID- 23866563
TI  - How is your discharge planning process?

PMID- 23866564
TI  - Measuring the next big thing.

PMID- 23866565
TI  - Shorter hours for interns can increase handoff risk.

PMID- 23866566
TI  - Working in real time. Selecting a cost-effective location system.

PMID- 23866567
TI  - A new front door. Expanding the hospital's reach with freestanding EDs.

PMID- 23866568
TI  - Enhancing the hospital visitor experience.

PMID- 23866569
TI  - Speaking their language. New report provides valuable communications tool.

PMID- 23866570
TI  - Best foot forward. Properly cleaning and maintaining a hospital floor.

PMID- 23866571
TI  - Flexible furnishings. Cost-efficiency, durability are king in reform era.

PMID- 23866572
TI  - [Transsphenoidal surgery of craniopharyngioma: form palliative surgery to radical
      removal].
AB  - The paper presents basic principles of transsphenoidal craniopharyngioma surgery.
      Stages of methodology development. Steps of methodology development of such
      operations in the Institute are described--from palliative interventions to the
      high-tech modern radical surgery with the use of anterior extended approach.
      Additional stereotactic irradiation provides reliable control of the disease for
      a long period. The article mainly describes operative technique and contains
      preliminary analysis of the surgical results showing effectiveness and safety of
      endoscopic removal of craniopharyngioma.

PMID- 23866573
TI  - [Endoscopic endonasal anterior extended transsphenoidal approach in
      craniopharyngioma surgery].
AB  - The paper describes results of treatment of 56 patients with suprasellar
      craniopharyngioma (stem, intra-extraventricular) who were operated in Burdenko
      Neurosurgical Institute using endoscopic endonasal anterior extended
      transsphenoidal approach. Assessed dynamics of major clinical syndromes (neuro
      ophthalmological symptoms, neurological and hormonal status), radicality of
      surgery, incidence and nature of postoperative complications, postoperative
      mortality. A comparative analysis of the results obtained in previous studies of
      our Institute, as well as with those of foreign authors is performed. Obtained
      data show that endoscopic endonasal anterior extended transsphenoidal approach in
      craniopharyngioma surgery is an efficient and non-traumatic technique, capable of
      providing a radical removal of the tumor along with a high quality of life after
      surgery, and relatively low rates of postoperative complications and mortality.

PMID- 23866574
TI  - [Long-term results of treatment of patients with large or giant intracranial
      aneurysms of internal carotid artery].
AB  - At Burdenko Neurosurgical Institute annually arrives 50-60 patients with large
      and giant aneurysms of the brain, which is nearly 15% of all patients with
      aneurysms. About half of them--patients with paraclinoid aneurysms, which are
      successfully treated by cliping using techniques of intravascular blood
      aspiration (IVBA) or proximal control of blood flow in the neck. This paper
      analyzes the long-term outcomes of patients who were operated for large and giant
      aneurysms of the internal carotid artery in the last 15 years. Catamnesis was
      collected from 93 (71.5%) of 130 patient. Mean follow-up was 65.2 +/- 36.0
      months. Mean age of patients at the time of surgery was 45.55 +/- 7.5 years and
      at the time of catamnesis evaluation 50.4 +/- 10.2 years. Men to women ratio was
      18:75. Patients with multiple aneurysms was 22.6% (21 patients). In most cases-
      67 (72%) patients--aneurysms were treated by cliping of aneurysms using IVBA, in
      14 (15%) cases--using proximal control of blood flow in the neck, in 5 (5.4%)
      cases--reinforced with gauze and glue, in 6 (6.5%) patient--by aneurysm trapping,
      in one case the aneurysm was not cliped. Radical surgery performed in 87 (93.5%)
      patients. Catamnesis analysis of survived patients showed that 55.8% of them are
      complaining of headaches, which they associate with the operation. 39 (43.3%)
      patients noted persistent elements of asthenia, 4 (4.6%) had sleep disorders, 5
      (5.8%) suffered of epileptic seizures and 1 (1.10%) of depression. Korsakoff's
      syndrome, developed after surgery in 2 (2.3%) patients remains. Only 38.4% of
      patients after surgery continue to work. Favorable outcome on the Glasgow outcome
      scale (4-5) was obtained in 81 (87.1%) patients, poor (2-3) in 5 (5.4%) patients.
      Mortality rate was 7.5%. Severe oculomotor disturbances have a slight tendency to
      recovery over time.

PMID- 23866575
TI  - [Surgical treatment of patients with chronic cerebral ischemia due to occlusion
      of the common carotid arteries].
AB  - The paper contains information about surgical occlusion of the common carotid
      arteries--one of the causes of chronic cerebrovascular ischemia. For the period
      from 2003 to the present time have been treated 25 patients with a clinical
      picture of cerebral ischemia due to occlusion of the common carotid artery.
      Performed a total of 48 surgical procedures among which subclavian-external
      carotid and common carotid bypasses, retrograde carotid thromboendarterectomy. In
      7 cases revascularization of the brain was performed as a second stage. Choice of
      reconstruction type based on preoperative investigation results and
      intraoperative data. No persistent complications or mortality were observed.
      Positive clinical dynamics was noted in 80% of cases. Crossability of
      reconstruction area at the annual catamnesis was 84%. Prosthetic vascular graft
      thrombosis occurred most often (up to 40%) in patients with type 2 occlusion and
      in the presence of severe collateral perfusion. In patients with 1st type of
      occlusion of the common carotid artery reconstructive surgery have shown to be a
      reliable and effective treatment for chronic cerebral ischemia and prevention of
      recurrent ischemic stroke.

PMID- 23866576
TI  - [Nanostructural analysis of the lumbar intervertebral disc on the various stages
      of degenerative process].
AB  - Intraoperative specimens of lumbar intervertebral disc (IVD) on the various
      stages of degeneration was studied by the method of atomic-force microscopy using
      hardware complex (probe nanolaboratory with video microscope Ntegra Prima). New
      nanostructural data, characterizing the staging of degenerative changes of IVD
      were revealed.

PMID- 23866577
TI  - [Breast carcinoma metastasis to the optic nerve: case report and review of
      literature].
AB  - Metastatic tumours of the optic nerve are extremely rare. The review of
      literature revealed only 12 cases of breast carcinoma metastasis to the optic
      nerve. All patients survived less then 6 month after surgical treatment. We
      describe a case of metastatic breast carcinoma to the optic nerve that occurred 8
      years after radical mastectomy followed by chemotherapy. The metastasis
      manifested with progressive decrease in visual acuity in the right eye during 3
      month. CT and MRI demostrated enhancing lesion in the muscle cone apex of the
      right orbit with an extension to the optic canal. The presumable diagnosis was
      optic nerve sheath meningioma, and surgical resection was performed. The tumour
      involved the optic nerve and has been resected togeher with the nerve. Histology
      report confirmed metastatic tumour. Postoperatively, the patient received
      additional stereotactic radiotherapy. Patient died of tumour dissemination 2,5
      years after surgery. Breast carcinoma metastases to the optic nerve usually have
      unfavorable prognosis both for survival and for visual acuity. Isolated
      metastatic tumors of the optic nerve remain a diagnostic challenge because of
      their clinical and radiological similarities to more common primary tumors of the
      optic nerve.

PMID- 23866578
TI  - [Turcot syndrome. Rare observation and literature review].
AB  - The Turcot syndrome is a rare disease which is characterized by a combination of
      a brain tumor with a y at which the neoplasm of the colon. About 150 of such
      observations are described in world literature. Our own observation and a
      literature review are presented in this article.

PMID- 23866579
TI  - [Management of postoperative analgesia in patients after craniotomy].
AB  - In a review paper, an analysis of publications in the world literature on the
      problem of acute postoperative pain in neurosurgical patients who underwent
      craniotomy is performed. Is shown that problem of acute postoperative pain in
      patients after craniotomy was underestimated for a long time. Mistakenly was
      thought that these patients do not experience any pain in the early postoperative
      period. Results of recent studies have shown that up to 80% of these patients may
      experience acute pain in the range from mild to severe. Unarrested postoperative
      pain could cause a number of serious secondary complications. This article
      demonstrates basic approaches to the prevention and treatment of acute
      postoperative pain in neurosurgical patients after craniotomy--first of all, the
      use of narcotic analgesics, NSAIDs, and other approaches.

PMID- 23866580
TI  - [My impressions of the three-volume edition "Modern technology and clinical
      research in neurosurgery" devoted to the 80th anniversary of Burdenko
      Neurosurgical Institute, edited by A.N. Konovalov. Moscow 2012].

PMID- 23866581
TI  - [Resistance of microorganisms of coastal ecosystems of the Dead Sea to extremal
      factors].
AB  - Such extreme factors as UV radiation, high temperature and salinity, and also the
      small amount of accessible water have an influence on microorganisms of coastal
      ecosystems of the Dead Sea. Resistance to these factors of the microorganisms
      isolated from ecosystems of this region (vertical steep gorge around the Dead
      Sea, clay-salt plain and black highly mineralized muds) is studied. Aerobic,
      chemoorganotrophic, thermotolerant, moderately halophilic bacteria which,
      according to their morphological and physiological properties, are similar to
      species Gracilibacillus halotolerans, Salimicrobium album and genus Caryophanon
      have been isolated from these ecosystems. All strains grew at 0-10% of NaCl in
      the medium (one strain--at 15% of NaCl), in the range of 30-50 degrees C.
      Resistance to UV radiation has been revealed in all the investigated bacteria
      Lethal doses of UV (LD90 and LD99.99) for spore-forming strains of genus
      Gracilibacillus were 100-170 and 1100-1500 J/m2, respectively; for strain
      Salimicrobium 6t1 (does not form spores)--70 and 400 J/m2; for the strain lt4
      (genus Caryophanon), forming filamentous (or trychomes)--150 and 1400 J/m2. Some
      strains of genus Gracilibacillus had strong antagonistic effect on conditionally
      pathogenic test cultures Staphylococcus aureus 209p and Candida albicans UCM Y
      690. It is conceivable that resistance of microorganisms of coastal ecosystems of
      the Dead Sea to extreme factors was generated under the influence of abiotic
      (physical and chemical) factors typical of this region.

PMID- 23866582
TI  - [Utilization of different carbon sources by soil and endophytic strains of
      Penicillium funiculosum Thom].
AB  - The ability of soil and endophytic strains of P. funiculosum to accumulate
      biomass under cultivation conditions in media containing carbon sources from mono
      to polysaccharides has been studied. It has been shown that the most favorable
      carbon sources for the studied strains were maltose, sucrose, xylose, fructose,
      pectin, less assimilated lactose, arabinose, and especially microcrystalline
      cellulose. Significant differences in the level of biomass accumulation between
      soil and endophytic strains of this species in most cases were not established.

PMID- 23866583
TI  - [Componential composition of chlororganic pollutants and state of soil microbial
      cenosis in soil from burial place of waste].
AB  - The authors have identified 25 chemical pollutants in soil and 12--in the
      chemical composition of technical waste from chemical production. Broad spectrum
      of pollutants and their degradation products (26 chemical components) have been
      also detected outside the proving ground (2 km). This fact evidences for active
      spreading of chlororganic toxins into neighboring areas. Abnormality in
      functional activity and functions of soil microbial cenosis of the proving ground
      has been established: the number of oligonitrophillus, ammoniating, phosphate
      mobilizing, amylolytic and pedotrophic microorganisms. Abnormalities of
      functional activity were manifested in the 1.6-1.9-fold augmentation of basal
      respiration and deterioration of substrate-induced respiration in comparison with
      control variant.

PMID- 23866584
TI  - [Influence of pH on synthesis of Acinetobacter calcoaceticus IMV B-7241
      biosurfactants].
AB  - Synthesis of extracellular metabolites with surface-active and emulsifying
      properties, pH being maintained at the level of 5.8-8.0, in the process of
      cultivation of Acinetobacter calcoaceticus IMV B-7241 in the medium with ethanol
      (2%, volume part) was investigated. It is established that the neutral value of
      pH is optimal for synthesis of surface-active substances (SAS, biosurfactants) of
      A. calcoaceticus IMV B-7241. The maintenance of pH at the level of 7.0 with the
      help of KOH solution was accompanied by the 1.8-fold increase of the amount of
      synthesized SAS as compared with the process indicators without regulation of pH.
      The substitution of KOH by NaOH to maintain pH at the optimal level led to the
      1.2-1.5-fold decrease of SAS concentration that is determined by the inhibiting
      effect of sodium cations on activity of biosynthesis enzymes of surface-active
      amino- and glycolipids of A. calcoaceticus IMV B-7241. The medium neutralization
      by KOH solution in the process of cultivation of the strain IMV B-7241 with
      further introduction of fumarate (0.01%) and citrate (0.01%) at the end of the
      exponential phase was accompanied by the 1.2-fold increase of the amount of
      synthesized SAS compared with the indicators of the analogous process without
      neutralization and by the 3 5-fold increase compared with bacteria cultivation on
      ethanol without organic acids and pH regulation.

PMID- 23866585
TI  - [Synthesis of extracellular phythohormones by Bacillus strains isolated from
      different ecological sources].
AB  - Synthesis of extracellular phytohormones by bacteria strains of the genus
      Bacillus isolated from different ecological sources (soil and plant) has been
      researched. It has been shown that phytohormone's synthesis ability of the
      endophytic and free-living Bacillus strains is significantly different as regards
      the level and spectrum of synthesized compounds. It was concluded that such
      differences in synthesis of extracellular phytohormones by bacilli are associated
      with different type of interactions between the studied microorganisms and host
      plant.

PMID- 23866586
TI  - The effect of Lacto- and Bifidobacteria in monoculture on the vaginal microflora
      in norm and in cases of intravaginal staphylococcosis.
AB  - The influence of probiotic strains of Lactobacillus casei IMV B-7280,
      Lactobacillus acidophilus IMV B-7279, Bifidobacterium animalis VKL, Lactobacillus
      delbrueckii subsp. bulgaricus IMV B-7281 and Bifidobacterium animalis VKB, each
      strain separately, to the range of the urogenital tract microflora in
      physiological norm and in cases of experimental intravaginal staphylococcosis of
      mice induced by Staphylococcus aureus 8325-4. It was found that all these strains
      had different efficiency in Staphylococcus aureus 8325-4 growth suppression in
      the vagina of infected mice and affect the spectrum of microorganisms.
      Lactobacillus casei IMV B-7280 strain had effective antistaphylococcal effect and
      reduced the number of coliform bacteria and fungi in the vagina in cases of
      intravaginal staphylococcosis of mice. Lactobacillus casei IMV B-7280 strain is
      promising to create probiotic drugs effective in treating intravaginal
      staphylococcosis.

PMID- 23866587
TI  - [Morphology and structural peculiarities of Basidiomycetes pathogens].
AB  - The materials of studies of morphology and structural peculiarities of viruses,
      fungi and bacteria, which affect Basidiomycetes under biotechnology process and
      nature biocenosis conditions are given. The analysis of infection development in
      button mushroom (Agaricus bisporus) (J.Lge) Imbach and in oyster mushroom
      (Pleurotus ostreatus Kumm.), which served as model objects in the experiments of
      various levels of complexity has been carried out. Other kinds of edible and
      medicinal mushrooms, which were a source of biochemical fractions to form
      biologicals were investigated.

PMID- 23866588
TI  - [Micrococcus sp.--the pathogen of leaf necrosis of horse-chestnuts (Aesculus L.)
      in Kiev].
AB  - A group of phytopathogenic bacteria was isolated from patterns of drying horse
      chestnuts (Aesculus L.), which grow in Kyiv. The properties of slowly growing,
      highly aggressive microorganisms have been described in the paper. They grow up
      on the 8-10th day after sowing. The investigated microorganisms form very small
      (0.5-1 mm in diameter) colonies on the potato agar. Bacteria are protuberant,
      shining, smooth with flat edges, they are pale yellow, yellow, or pink. The
      bacteria are Gram-positive, spherical, are disposed in smears singly, in pairs,
      as accumulations, or netting. They are aerobes, do not form spores, are not
      mobile. They are inert in respect of different sources of carbon. They reduce
      nitrates, do not dilute gelatin, do not hydrolyze starch, do not release hydrogen
      sulphide and indole. The bacteria are catalase-positive, oxidase-negative. They
      do not cause potato and carrot rot. They lose quickly their viability under the
      laboratory conditions. The saturated acids C 14:0; C 15:0; C16:0; C18:0 have been
      revealed in the composition of cellular fatty acids. Microorganisms are
      identified as Micrococcus sp. Under artificial inoculation this highly aggressive
      pathogen causes drying of the horse-chestnut buds and necrosis, which occupies
      1/3-1/2 of the leaf plate. A wide zone of chlorosis, surrounding necrosis, may
      occupy the whole leaf surface. The infected leaves use to twist up from the top
      (apex) or along a midrib and to dry.

PMID- 23866589
TI  - [The characterization of bean yellow mosaic virus isolated from soybean].
AB  - The comparative characteristics of biological, physico-chemical and antigenic
      properties of bean yellow mosaic virus isolated from soybeans are shown. The
      obtained results indicate the existence of individual properties of the isolate
      which help to distinguish it from the typical strains and isolates studied
      previously in Ukraine by other authors.

PMID- 23866590
TI  - [Effect of host change on phages 223 -17 and 7591-14 Pseudomonas savastanoi pv.
      tabaci].
AB  - We studied the characteristics of phages 223-17 7591-14 grown on the strains of
      Pseudomonas syringae pv. tabaci, on the intermediate host of P. savastanoi pv.
      phaseolicola and after their returning to original. It was found, that phages
      grown on pv. phaseolicola acquired ability to cause lysis of previously resistant
      strains P. viridiflava (phage 223-17) and P. fluorecens (phage 7591-14). It was
      common that, when making the restriction analysis of DNA of phages grown on pv
      tabaci, the formation of additional minor fragments was observed along with the
      major fragments. Phage DNA did not change its length then. Two minor EcoRV
      fragments of DNA identical by length, were found in both phages in the first
      studies. If they changed the host, they disappeared. Once again returning to the
      first host the authors found previously absent, additional minor HindIII
      fragments of DNA. The phage 7591-14 had two fragments, while the phage 223-17 had
      one fragment. Formation of minor EcoRV DNA fragments is obviously connected with
      the emergence of an additional restriction site, since the sum of their lengths
      is equal to the size of one of the major fragments. Minor HindIII fragments whose
      size was equal to the sum of the lengths of two and three major fragments could
      be formed as a result of the loss of several restriction sites. Since the effect
      of the host enzyme systems on phage DNA was accompanied by the synchronous
      acquisition or loss of minor DNA fragments, it is obvious that this process is
      not of a random nature. Weak luminescence of the minor fragments of considerable
      length indicates that their part in the total pool of DNA is small. The observed
      changes of phages seem to be associated with the process of their adaptation to
      different hosts.

PMID- 23866591
TI  - [Fibrinolytic peptidases of Bacillus].
AB  - The fibrinolytic enzymes are peptidases, which belong to the class of hydrolytic
      enzymes. They are able to dissolve the insoluble fibrin. This review presents the
      fibrinolytic peptidases of Bacillus. The methods of increasing biosynthesis of
      these enzymes, determination of their activity, isolation and purification have
      been observed. The fibrinolytic peptidases of Bacillus are serine- and
      metallopeptidases. Its can hydrolyze both the natural substrates (fibrin,
      fibrinogen and hemoglobin) and synthetic substrates. The high stability of these
      enzymes in a wide range of pH (5-12) and temperature (10-75 degrees C) permits
      using them in pharmacology, medicine for the prevention and treatment of
      cardiovascular diseases.

PMID- 23866592
TI  - [Nephropathy in Fabry disease: possibilities for the radical improvement of
      prognosis for orphan diseases].
AB  - The paper discusses the specific features of the diagnosis and treatment of
      kidney involvement in patients with Fabry disease.

PMID- 23866593
TI  - [Diagnostic value of cystatin C and neutrophil gelatinase-associated lipocalin in
      primary glomerulopathies].
AB  - AIM: To study an association between clinical and morphological evidence and the
      serum and daily urinary levels of cystatin C (CysC) and neutrophil gelatinase
      associated lipocalin (NGAL) in patients with primary glomerulopathies. SUBJECTS
      AND METHODS: The investigation included 104 patients; morphological examination
      showed minimal change disease in 15 (14.4%) patients, focal segmental
      glomerulosclerosis in 24 (23.1%), membrane nephropathy in 32 (30.8%), and IgA
      nephropathy (mesangioproliferative glomerulonephritis) in 33 (31.7%). The
      investigators analyzed the clinical type of nephropathy, performed conventional
      laboratory and instrumental examinations, and determined the level of CysC (by
      immunoturbodimetry) and NGAL (by enzyme immunoassay) in the serum and daily urine
      taken before kidney biopsy. The degree of glomerulosclerosis,
      tubulointerstititial sclerosis, and tubular atrophy was semiquantitatively
      estimated. RESULTS: Urinary CysC and NGAL excretion correlated with the degree of
      glomerulosclerosis and proteinuria and the reduced glomerular filtration rate
      (GFR) regardless of the method of its determination. The urinary level of NGAL
      positively correlated with the degree of tubular atrophy. The GFR value
      determined from serum CysC and creatinine levels more precisely reflected the
      degree of glomerulosclerosis. CONCLUSION: The tubulointerstitial compartment in
      primary glomerulopathies should be determined not only by morphological changes,
      but also by tubular function parameters by estimating the urinary excretion of
      biomarkers. The urinary content of CysC reflects tubular epithelial dysfunction
      whereas that of NGAL also characterizes tubular atrophy. To estimate the degree
      of glomerulosclerosis, it is more preferable to use the GFR calculated from the
      blood concentrations of CysC and creatinine, by keeping in mind clinical findings
      (using Chronic Kidney Disease Epidemiology Collaboration formula, 2012).

PMID- 23866594
TI  - [New markers of cardio-renal links in chronic kidney disease].
AB  - AIM: To study the clinical significance of determining the serum concentration of
      phosphorus and calcium metabolism regulators--the morphogenetic proteins FGF-23
      and Klotho in patients with different stages of chronic kidney disease (CKD).
      SUBJECTS AND METHODS: The serum levels of FGF-23 (a human FGF-23 ELISA kit with
      full-length anti-FCF-23 monoclonal antibodies) and Klotho (a human alpha-K1 ELISA
      with anti-Klotno antibodies) were investigated in 70 patients with Stages I--VD
      CKD (41 patients with chronic glomerulonephritis, including 10 with nephritis in
      systemic diseases, 22 with tubulointerstitial nephritis, and 7 with hypertensive
      nephroslerosis). The morphogenetic proteins were studied by the specialists of
      the LiTECH diagnostic laboratory according to the standard protocol. RESULTS: As
      CKD progressed from Stage I to VD, there were increased FGF-23 concentrations and
      decreased Klotho levels in the examinees' serum. The highest FGF-23 level and low
      Klotho concentration were noted in the group of patients on regular hemodialysis
      treatment (Stage VD). There was a strong inverse correlation between Klotho
      levels and proteinuria, C-reactive protein, and protein-energy insufficiency,
      which suggests that these factors influence the serum level of Klotho. The serum
      levels of FGF-23 and intact parathyroid hormone correlated with these values to a
      lesser degree. Analysis of the content of the morphogenetic proteins in patients
      with anemia versus those with CKD of the same stages and target hemoglobin values
      revealed low Klotho concentrations and high FGF-23 levels (r = 0.602; p < 0.01
      and r = -0.450; p < 0.01, respectively). Forty-nine hypertensive patients showed
      a direct strong relationship between elevated serum FGF-23 levels and an inverse
      strong one between the reduced serum Klotho levels and the increased posterior
      left ventricular wall (r = 0.552; p < 0.01 and r = -0,587; p < 0.01,
      respectively). The same strong association was found between the higher serum
      level of FCF-23 (r = 0.492; p < 0.01) and the concentration of Klotho (r = 
      0.537; p < 0.01) and peripheral vascular resistance index (as evidenced by
      Doppler ultrasound study). CONCLUSION: Along with the active participation of the
      morphogenetic proteins (FGF-23 and Klotho) in mineral metabolism and its
      disturbances in CKD, their role is apparent in the development of cardiovascular
      events (in particular, through the involvement in the processes of vascular
      calcification and cardiac remodeling), anemia (through the possible effect on
      iron metabolism, enhanced ischemia of renal interstitial tissue with impaired
      Klotho production), and protein-energy insufficiency (through the participation
      in the processes of inflammation, oxidative stress, and protein synthesis).

PMID- 23866595
TI  - [Specific features of cognitive impairments in patients with predialysis chronic
      kidney disease].
AB  - AIM: To study the specific features of cognitive impairments (CI) in patients
      with predialysis chronic kidney disease (CKD). SUBJECTS AND METHODS: Examinations
      were made in 51 patients aged 52 +/- 10 years with CKD, including 20 patients
      with Stages I-II CKD (glomerular filtration rate (GFR) > or = 60 ml/min/1.73 m2;
      signs of kidney lesion), 20 with Stage III (GFR 60-30 ml/min/1.73 m2), and 11
      with Stage IV (GFR 30-15 ml/min/1.73 m2). GFR was estimated using the
      Modification of Diet in Renal Disease (DMRD) formula. The authors made a
      questionnaire survey to identify day-to-day activity limitations and depressions
      and performed neuropsychological tests using the mini-mental state examination
      (MMSE), a frontal assessment battery (FAB) for frontal lobe dysfunction, a short
      term and delayed memory test (Luria's 10 words test), and a regulatory function
      assessment test (RFAT). Magnetic resonance imaging (MRI) was carried out to
      clarify the etiology of CI. RESULTS: CI was detected more frequently in the
      patients with chronic renal failure (CRF) (Stages III-IV CKD) than in those
      without CRF (Stages I-II CKD) (in 90.3 and 35%, respectively (p < 0.001)). CI was
      statistically significantly more frequently found using MMSE (p < 0.001), FAB (p
      = 0.001), and RFAT (p < 0.001). There was a statistically significant rise in the
      magnitude of CI with the higher stage of CKD, as shown by MMSE, FAB, and RFAT,
      other than the short-term and delayed memory test. Brain MRI in the patients with
      CI revealed focal changes in 9 (30%) patients, leukoaraiosis in 7 (23.3%),
      lateral cerebral ventricular dilatation in 15 (50%), and markedly dilated
      hemispheric sulci in 3 (10%). CONCLUSION: The higher stage of CKD is associated
      with the increased incidence and magnitude of CI, as evidenced by MMSE, and with
      those of anterior brain dysfunctions. The comparisons of clinical and MRI
      findings suggest that cerebrovascular disorders underlie CI in CKD.

PMID- 23866596
TI  - [Significance of the factors of hypoxia and endothelial dysfunction in kidney
      injury in the presence of obesity].
AB  - AIM: To define the clinical significance of asymmetric dimethylarginine (ADMA)
      and that of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism as
      factors of endothelial dysfunction (ED) in the development of early kidney injury
      in obese patients. SUBJECTS AND METHODS: The investigation included 86 patients
      (64 men and 22 women aged 44 +/- 11 years) with abdominal obesity. Along with
      physical examination, the authors determined albuminuria, calculated glomerular
      filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD)
      formula, estimated insulin resistance markers (fasting plasma insulin and C
      peptide concentrations and homeostatic model assessment (HOMA) index), as well as
      serum ADMA levels by enzyme immunoassay in all the patients. C677T polymorphism
      in the MTHFR gene was studied by allele-specific polymerase chain reaction and
      restriction fragment length polymorphism analysis. Kidney injury (chronic kidney
      disease (CKD)) was diagnosed using the Kidney Disease Outcomes Quality Initiative
      (KDOQI) criteria. Early vascular remodeling was determined from the increased
      intima-media thickness (IMT) of the common carotid artery (CCA). RESULTS: CKD was
      diagnosed in 27(31%) patients. The latter, unlike the patients with CKD, were
      observed to have more pronounced obesity (body mass index (BMI) 36.8 +/- 8.0 and
      32.0 +/- 4.7 kg/m2, respectively (p < 0.001)), waist circumference (119 +/- 18
      and 109 +/- 11 cm (p = 0.002)), higher levels of C-peptide (1348 +/- 363 and 1028
      +/- 363 pmol/I; p < 0.001), insulin (16.9 +/- 7.3 and 11.7 +/- 5.5 microU/ ml; p
      < 0.001), and HOMA index (4.3 +/- 1.7 and 2.9 +/- 1.5; p < 0.001). In the
      patients with Stage IIIa CKD, ADMA concentrations (0.77 +/- 0.19 micromol/l) was
      higher than in those with Stages I (0.58 +/- 0.11 micromol/l; p = 0.048) and II
      (0.61 +/- 0.13 micromol/l; p = 0.071). An association between ADMA
      concentrations, CCA IMT, and estimated GFR was revealed in the patients with CKD.
      The predictors of an estimated GFR reduction in obesity were elevated serum
      concentrations of ADMA, uric acid, insulin, and HOMA index. The combination of
      obstructive sleep apnea syndrome and metabolic syndrome increased the risk of CKD
      by 2.1-fold (95% confidence interval, 1.06-3.14). Evaluation of the impact of
      MTHFR gene polymorphism on kidney injury in obesity disclosed that the patients
      with homozygous carriage of the abnormal T allele of the MTHFR gene had a higher
      risk for Stages I-IIIa CKD (2.60 with 95% confidence interval, 1.32-3.88), more
      marked obesity and hyperinsulinemia, and increased serum ADMA concentrations.
      CONCLUSION: Insulin resistance and ED hold a central position in the pathogenesis
      of CKD in obese patients. The mechanisms of the atherosclerotic vascular
      remodeling associated with elevated serum ADMA concentrations are of paramount
      importance in the progression of early-stage CKD. The homozygous carriage of the
      abnormal T allele of the MTHFR gene increases the risk of Stages I-IIIa by more
      than twice.

PMID- 23866597
TI  - [Test strip evaluation of albuminuria for the early detection of chronic kidney
      disease in persons with different risks (the experience of the Health Centers of
      the Moscow Region)].
AB  - AIM: To evaluate albuminuria (AU) in the Moscow Region's dwellers visiting the
      health centers and to clarify its association with the proven and discussed risk
      factors (RF) of chronic kidney disease (CKD). SUBJECTS AND METHODS: A total of
      1623 patients (390 (24%) men and 1233 (76%) women; mean age 46 +/- 16 years) were
      examined. Urinalysis using test strips was performed in all the examinees. AU was
      estimated by the following scale: normal AU (NAU) (< 10 mg/l), an initial
      increase (11-30 mg/l), a pronounced increase (31-300 mg/ml), very high AU (> 300
      mg/ml). A questionnaire covering gender, age, patients' anthropometric data,
      comorbidities, healthy lifestyle adherence, and smoking was designed to assess
      possible RFs for CKD. Body mass index (BMI) was calculated. Medical history
      examination showed metabolic disturbances and cardiovascular diseases. RESULTS:
      The detection rate of NAU was 18%; the initial and pronounced increases were
      found in 40 and 41% of the examinees, respectively; the very high AU was in 1%.
      The first questionnaire items associated with AU > 30 mg/ml were complaints of
      edema, sternal pain, poor appetite, meat aversion, and constant thirst. The
      detection rate of AU > 30 mg/l in hypertensive persons was 51%. If the patients
      had diabetes mellitus or a history of increased blood glucose episodes, the
      detection rate of AU > 30 mg/l amounted to as much as 65.5%. Estimation of
      overweight and obesity indicated that AU of > 30 mg/l was found in 44 and 49% of
      cases, respectively (p < 0.001). Analgesic abusers, long-term smokers, and
      sedentary people were statistically significantly more frequently found to have
      AU of > 30 mg/l. CONCLUSION: The pronounced and very high AU was noted in more
      than 40% of those who had visited the health centers. A questionnaire survey
      makes it possible to reveal a variety of AU increase-associated factors that
      primarily reflect metabolic disturbances and cardiovascular diseases and to
      identify a risk group in order to study AU first. Particular emphasis should be
      placed on the examinees' lifestyle. Healthy lifestyle non-adherence is closely
      correlated with increased AU and may be regarded as a RF for CKD.

PMID- 23866598
TI  - [Diastolic dysfunction in different types of left ventricular hypertrophy in
      patients with end-stage renal failure: impact of long-term erythropoietin
      therapy].
AB  - AIM: To study the specific features of diastolic dysfunction (DD) in different
      types of left ventricular (LV) hypertrophy (LVH) in patients with end-stage renal
      failure (ESRF) and to estimate the cardioprotective effect of erythropoietin.
      SUBJECTS AND METHODS: 107 patients (57 women and 50 men) aged 22 to 63 years with
      ESRF were examined. The follow-up was 18 months. LV ejection fraction, peak early
      diastolic filling rate, peak late diastolic filling rate, their ratio, LV
      isovolumic relaxation time, LV end-diastolic diameter, LV end-diastolic volume,
      LV end-diastolic diameter index (EDDI), LV posterior wall and ventricular septal
      thickness, and LV mass index were determined. J. Gottdiener's classification
      based on the calculation of EDDI and LV relative wall thickness was used to
      estimate LV geometry. Erythropoietin was given to patients with the baseline
      level of hemoglobin (Hb) < 110 g/l or hematocrit (Ht) < 33%; and iron (III)
      hydroxide sucrose complex was used to those with ferritin < 100 microg/l or
      transferrin saturation < 20%. The target level of blood pressure was 130/80 mm
      Hg; Hb was less than 110 g/l for women and 120 g/l for men; Ht, > 33%. RESULTS:
      The patients with ESRF were found to have different types of DD and LVH, the
      severity of which correlated with the magnitude of renal anemia and arterial
      hypertension (AH). Adequate correction of anemia and AH promoted the transition
      of more to less severe DD and LVH and in a number of cases the recovery of LV
      structure and function. CONCLUSION: ESRF is characterized by different types of
      DD, which are pathogenetically closely related to different types of LVH.
      Adequate correction of renal anemia and AH may cause a significant reduction and,
      in a number of cases, alleviate VLH, and normalize LV systolic and diastolic
      functional values.

PMID- 23866599
TI  - [Cardiorenal links in systemic amyloidosis].
AB  - The paper gives current general data on the structure of amyloid fibril and the
      principles in the classification of amyloidosis, information on the clinical
      course of cardiac and renal involvements in systemic AL and AA amyloidosis, and
      that on diagnostic and prognostic criteria and the specific features of
      cardiorenal links. The authors draw the conclusion that the identification of
      acute and chronic cardiorenal links is of practical value for systemic
      amyloidosis. Cardiorenal and renocardiac syndromes are not always differentiated
      clearly in the systemacy of involvement.

PMID- 23866600
TI  - [Time course of changes in iron metabolic and oxidative-antioxidative system
      parameters in patients with acute myeloid leukemia].
AB  - AIM: To study an association between iron metabolism, free radical oxidation
      (FRO), and antioxidative system (AOS) in patients with acute myeloid leukemia
      (AML) during intensive chemotherapy. SUBJECTS AND METHODS: AML patients (n = 14)
      with a median age of 46 years received 7+3 courses (n = 3) containing cytarabine
      > or = 1 g/m2/introduction (n = 8) and myeloablative conditioning regimen before
      hematopoietic stem cell transplantation (n = 3). The concentrations of iron,
      ferritin, transferrin saturation (TFS), and malonic dialdehyde and the activity
      of superoxide dismutase (SOD), ceruloplasmin (CP), and catalase were investigated
      in their sera. The investigations were performed before and after chemotherapy
      and during hemopoietic recovery and rehospitalization. RESULTS; After therapy
      termination, there was a significant increase in TFS (6.8% vs 41.9%; p < 0.0001),
      which gave way to its reduction during hemopoietic recovery (89.5% vs 96.8%; p =
      0.003). The activity of antioxidant enzymes was found to be altered at a time.
      That of catalase was enhanced throughout cytopenia (3.8 and 3.3 vs 5.7
      conventional units (CU)/ml; p = 0.028 and p = 0.011). The lower activity of SOD
      (21.0 vs 41.0 CU/ml; p = 0.018) and the higher activity of CP (1.1 vs 0.8 g/l)
      were ascertained when leukocyte count increased up to > or = 1 x 10(9)/l.
      CONCLUSION: After intensive cytostatic therapy, there was a phasic TFS increase
      accompanied by the compensatory change in AOS activity, which is aimed at
      neutralizing FRO products.

PMID- 23866601
TI  - [General molecular and cellular mechanisms for renal and cardiac remodeling in
      chronic kidney disease: a target for nephrocardioprotection].
AB  - The lecture considers a number of molecular and cellular mechanisms underlying
      the structural and functional rearrangement and development of renal and cardiac
      fibrosis in chronic kidney disease (CKD). It details the key component of
      disadaptative organ remodeling (the formation of myofibroblasts via epithelial
      mesenchymal and endothelial-mesenchymal transdifferentiation) and the role of
      leading angiofibrogenic mediators (angiotensin II, transforming growth factor
      beta type 1, a plasminogen activator inhibitor type 1, etc.) in the regulation of
      these processes. Investigation of the molecular and cellular bases of organ
      fibrosis, including the factors of dysregulated activation, differentiation and
      survival of microfibroblasts, makes it possible to specify the mechanisms of
      action of traditional nephro- and cardioprotective agents, to offer a possibility
      for a goal-oriented (target) effect on individual fibrogenic components, and to
      expand the arsenal of medications suppressing renal and cardiac remodeling.

PMID- 23866602
TI  - [Efficiency and safety of lipid-lowering therapy for chronic kidney disease].
AB  - The paper considers the problem of lipid-lowering therapy for chronic kidney
      disease, by using different groups of drugs, the expediency, efficiency, and
      safety of the therapy at different disease stages, including end-stage renal
      failure, and replacement treatments.

PMID- 23866603
TI  - [Hepatitis C virus-related cryoglobulinemic vasculitis with renal involvement:
      current possibilities of treatment].
AB  - The paper considers the specific features of renal involvement developing in
      chronic infection caused by hepatitis C virus (HCV) and the current possibilities
      of treatment. It details the clinical and morphological manifestations of HCV
      related cryoglobulinemic glomerulonephritis, and criteria for its diagnosis and
      prognosis. The author discuss new approaches to treating (severe cryoglobulinemic
      vasculitis with renal involvement in particular)--antiviral therapy (pegylated
      interferon-alpha/ribavirin) in combination with biological agents (anti-CD
      monoclonal antibodies, such as rituximab) to achieve clinical, virological,
      immunological remissions and a response at a molecular level--to eliminate oligo-
      and monoclonal B lymphocyte proliferation.

PMID- 23866604
TI  - [Factors for the development and progression of cardiorenal complications in
      women].
AB  - The paper describes the state-of-the-art of risk factors for cardiorenal
      complications in women. It is shown that while managing women of reproductive,
      menopausal, and menopausal ages, great importance should be attached to the
      assessment of all risk factors for the development and progression of chronic
      renal and cardiovascular diseases. Investigations of the specific features of
      these factors in women, their enrollment along with men in large-scale randomized
      trials will serve as a basis for developing more effective programs for the
      prevention and therapy for cardiovascular and renal diseases and hence will be
      able to reduce disability rates, to increase quality of life, and to prolong its
      span.

PMID- 23866605
TI  - [Psychophysiological signs of high-flexible forms of set on the emotionally
      negative facial expression].
AB  - In a series of studies of influence of past experience on an recognition of
      emotionally negative facial expression where obtained experimental facts which we
      consider as the formation signs of under certain conditions high-plastic
      cognitive (flexible) sets ("not fixed sets", according to D.N. Uznadze) when
      there switching or updating was not accompanied by illusory distortion of
      recognition. The studies of this form of set revealed: 1--the induced reaction of
      synchronization of a teta-rhythm to target stimulus was larger, than in cases
      with rigid set; 2--the induced reaction of an alpha rhythm to target stimulus is
      expressed in its synchronization, at the others cases--in a desynchronization; 3-
      at increase in a time interval between target and trigger stimuli observe alpha
      rhythm synchronization in the prestimulus period and in time intervals between
      them, at other cases it wasn't observed; 4--at children this form of set observed
      at the age of 10-11 years when "mature" set on an facial expression is formed.

PMID- 23866606
TI  - [Motor imagery and its practical application].
AB  - The mechanisms underlying the process of motor imagery are similar to the motor
      control mechanisms. It can be used for motor learning in patients with movement
      disorders. Motor imagery may be the only one method for recovery of motor
      function in patients with severe paresis. It was the prerequisite of increased
      scientist interest in motor imagery during last decade. Brain-computer interface
      technology can support the motor imagery trainings.

PMID- 23866607
TI  - [Comparison of its and orientation tuning dynamics in neurons located in
      different functional domains of cat's primary visual cortex].
AB  - Orientation tuning and its dynamics of cat's primary visual cortex neurons
      located in pinwheel centers and orientation columns were studied during
      development of response in time. Functional domains in the Cortex were revealed
      by intrinsic signal optical imaging on functional and vascular maps of cortex.
      Both maps were used for precise placement of electrodes during recordings.
      Orientation tuning dynamic of each neuron was analyzed by temporary slices
      technique. Several types of neurons were observed in different functional
      domains: neurons with stable preferred orientation (14.5%); cells with preferred
      orientation dynamically shifted by 102 +/- 5 degrees (40.8%) and neurons with
      mixed dynamics type (44.7%). In pinwheel centers neurons with stable preferred
      orientation are differed from neurons with unstable preferred orientation in
      their features. In particular, they are showing greater response strength for
      preferred orientation. In orientation columns neurons with stable tuning are
      demonstrating larger latent periods for all orientations including preferred and
      non-preferred in comparison to cells with unstable response dynamics. We observed
      better detection quality of stable orientation neurons than in unstable preferred
      orientation neurons. Further coding features of neurons belonging to one
      functional type but located in different domains were compared. In general,
      located in pinwheel centers stable neurons have shorter latencies and stronger
      responses than for the stable cells located in orientation columns. Detection
      features were similar for this functional type of neurons. Unstable neurons
      located in different functional domains don't differ from each other in
      orientation tuning characteristics. Functional significance of neurons with
      stable and unstable preferred orientation located in pinwheel center and
      orientation columns in visual information processing are discussed.

PMID- 23866608
TI  - [Intelligence and creativity changes induced by pathological growth of space
      occupying cerebral lesion].
AB  - Creativity and intelligence changes depending on tumor localization in frontal or
      parietal cortex before surgical procedure in 24 patients in comparison with
      control group are studied. Brain damage-induced intelligence impairment and a
      decrease of fluency, flexibility of figural divergent thinking, and originality
      of verbal one without specificity of tumor localization were found. Intelligence
      decrease was more presented while performing of figural tasks and least of all in
      verbal ones. The left prefrontal brain damage induced a decrease of all
      components of intelligence and a trend to a decrease of verbal creativity and
      figural fluency. The right parietal brain lesion was more associated with a
      decline of divergent thinking originality.

PMID- 23866609
TI  - [Possibility of memory reparation: conditioned freezing disrupted by protein
      synthesis inhibition can be restored by reminder stimulation in mice].
AB  - Memory consolidation is a term used to describe the process of memory
      stabilization from labile, easily disrupted state into disruption-resistant long
      term form. Protein synthesis inhibitors injected before or immediately after
      learning episode, produce significant amnesia. However in a limited number of
      studies the possibility of memory recovery after such pharmacologically-produced
      amnesia was shown. The aim of present study was to investigate the possibility of
      memory recovery in single-session fear conditioning paradigm in mice. Mice were
      injected with protein synthesis inhibitor cycloheximide twenty minutes prior
      learning to induce amnesia. Twenty four hours after training mice were subjected
      to reminder shock, similar to one used during training. Amnestic animals have
      demonstrated complete recovery of cued fear memory to the level of normal animals
      when tested 24h after reminder presentation. Thus our data indicate that specific
      type of memory might be restored using nonspecific stimulus as a reminder.
      Possible mechanisms of memory reparation after PSI injection during learning are
      discussed.

PMID- 23866610
TI  - [Development of movement disorders in DBA/2J male mice under repeated experience
      of aggression].
AB  - Changes in the behavior of DBA/2J mice after gaining repeated experience of
      aggression have been investigated. It was shown that the long-term experience of
      aggression led to development of hyperactivity estimated as increased motor
      activity in different tests: open field, elevated plus maze and during testing of
      reaction to a novelty. Symptoms of attention deficit estimated in the "partition"
      test as a reduction of the communicativeness and the lack of reaction to
      unfamiliar partner were noticed. Appearance of a large number of hyperkinesis
      manifested most often in the form of sudden involuntary head movements (jerks)
      was observed in the behavior of aggressive males during agonistic interactions.
      Most of the changes in the behavior of DBA/2J mice differed significantly from
      previously detected in the behavior of aggressive mice of C57BL/6J and CBA/Lac
      strains, suggesting a significant contribution of heredity that determines the
      features of behavioral disorders that occur under the influence of long-term
      experience of aggression. Similarity of symptomatics of movement disturbances in
      mice and in humans with some neurological diseases is discussed.

PMID- 23866611
TI  - [Effect of agonists and antagonists of 5-HT2 receptors on rats with different
      choice of reinforcement value].
AB  - The influence of drugs, agonist (DOI) and antagonist (ketanserin) ofserotonin
      receptors 5-HT2 on the behavior of rats tested by the method of choice to the
      value of reinforcement was investigated. Depending on their preferences in food
      reinforcement rats were divided into self-control (choosing more valuable,
      delayed reinforcement) and impulsive (low value, immediate reinforcement) groops.
      An hour before the test animals were administrated i.p. DOI and ketanserin at a
      dose of 0.2 mg/kg. Evaluated parameters of rat behavior: number of clicks on a
      particular pedal, the latencies and the number of omitted responses. The
      administration of ketanserin resulted in a statistically significant decrease in
      the choice of low-value immediate reinforcement of impulsive rats, and did not
      statistically significant alter the behavior of self-control animals. After the
      administration of DOI no statistically significant changes in the choice of
      reinforcement were observed in the groups of impulsive and self-control rats. But
      the study of the effect this drug in tote without division into typological
      groups the decreasing in impulsivity was revealed. In some cases DOI reduced the
      number of missing responses, and ketanserin--reduced the latency of response.

PMID- 23866612
TI  - [Role of serine/threonine and tyrosine protein phosphatases in command Helix
      lucorum neurons at the cellular correlate of habituation].
AB  - Effects of some inhibitors of serine/threonine and tyrosine protein phosphatases
      on the depression and spontaneous recovery of the acetylcholine-induced inward
      current (ACh-current) in command Helix neurons of defensive behavior at the
      cellular correlate of habituation were investigated. The following drugs were
      used: okadaic acid (reduces activity ofphosphatases PP1 and PP2A), endothall
      (PP2A), cyclosporine A and cypermethrin (PP2B), CCT007093 (PPM1D), dephostatin
      (blocks tyrosine phosphatases). All used inhibitors modify the depression flow,
      and endothall reduces spontaneous recovery of ACh-current also. Obtained results
      indicate that changes in cholinosensitivity of command neurons depend on activity
      of all investigated protein phosphatases. Mathematical model considers the
      possibility of different localizations of receptors in a neuron and regularity of
      transitions between them. This model makes it possible to conclude participation
      indicated phosphatases in mobility of membrane cholinoreceptors ensuring the ACh
      current modification at the cellular correlate of habituations. Comparison of
      experimental and calculated curves of ACh-current change allows to conclude that
      the main target of protein phosphatases is the transport system of a neuron-
      cytoskeleton and motor proteins.

PMID- 23866613
TI  - [Neuron activity of cortex and striatum at animals in the situation with "right
      of choice" of reinforcement].
AB  - In behavior model of "right of choice" of value of appetitive reinforcement
      animals have classified in self-control, ambivalent and impulsive groups based on
      significant distinctions in displays of short delayed or long delayed reflexes.
      The organization of functional cross correlation interneuron interactions in
      frontal, visual, motor cortical areas and dorsal part of caudatus have estimated
      at realization short delayed, long delayed reflexes and errors. Similarity and
      distinctions in the organization of network activity were analyzed. It was shown
      that only interneuron relation of visual cortex and caudatus were similar for
      impulsive and self-control animals. When comparing the "impulsive" and
      "ambivalent" animals similarity was found in the network activity of neurons of
      visual, motor cortex and dorsal part of caudatus. The differences in the network
      activity in the frontal cortex were identified between animals of all three
      groups during realization of long delayed reflexes.

PMID- 23866614
TI  - [Distinctive features of the anxiety state development in experimental model of
      posttraumatic stress disorder in the prenatally stressed male rats].
AB  - Anxious-depressive state was studied in experimental "stress-restress" model of
      posttraumatic stress disorder (PTSD) using adult rat males. Rat males were born
      by control females and whose mothers were under 60-minute immobilization stress
      since 15 until 19 days of pregnancy. Then rats were exposed to a single session
      of prolonged stress (restraint followed by a forced swim and exposure to ether
      vapors) and restressed 7 days later. 10 and 20 days after restress animals were
      tested in elevated plus-maze to measure anxiety and forced swim test to research
      depression-like behavior. In both groups there were control animal that stay
      intact. In addition to behavior, we studied activity of hypothalamo-pituitary
      adrenal axis (basal activity and fast feedback inhibition) by analysis of plasma
      corticosterone concentration. We found that in control and prenatally stressed
      (PS) rat males in 10 days after stress have pathological state such as elevated
      anxiety and depressive-like behavior and inhibition of stress activity of H PA
      axis due to activation of fast feedback. However, in PS rats signs of disorder
      were deeper and longer--decreased basal plasma corticosterone and increased
      anxiety those saved in 20 days after restress. In conclusion, we can say that
      prenatal stress promotes developing of stronger behavioral and hormonal pathology
      in "stress-restress" paradigm.

PMID- 23866615
TI  - [On the life cycle and morphology of metacestodes Dioecocestus asper
      (Cyclophyllidea: Dioecocestidae)].
AB  - Metacestodes Dioecocestus asper (Cyclophyllidea) habe been found in larvae of
      dragonflies Aeshna spp. (Odonata, Anisoptera) from the lakes of the Upper Kolyma
      and northern Okhotsk seaboard basins (3.8 +/- 0.46 % of n = 1730 and 0.09 +/-
      0.09 % of n = 1065, respectively) for the first time. Thus, participation of
      dragonflies in lifecycle of Dioecocestidae has been proved. Larvagenesis of D.
      asper (from spontaneously infested hosts) have been retraced from the stage of
      primary lacuna up to fully-developed metacestode. Process of development of the
      metacestode D. asper includes two invaginations. The first one follows the start
      of exogenous formation of undifferentiated anlage of the cystoscolex; as the
      result, the latter settles to the bottom of the forming two-layered exocyst
      homologous to the cercomer. Subsequent development of the prospecive part and the
      endocyst occurs in the closed amniotic cavity of the sacciform exocyst, the back
      pole of which preserves embryonic hooks and the front pole possesses the
      invaginational channel. At the stage of early scolexogenesis, the endocyst with
      the anlage of the strobila and the scolex separates from the exocyst and the
      excretory atrium forms on the back pole of endocyst. At the stage of late
      scolexogenesis, the formation of the larval strobila (differentiation of the sex)
      is completed and the second invagination starts. Strong retractors pull bottom of
      the stribila into the endocyst; simultaneously, the front part of it is also
      turned inside. The invaginational pore of the endocyst of fully-developed
      metacestode D. asper remains open; the scolex with the most part of the strobila
      is located outside the endocyst in the cavity of the exocyst. The encystment of
      the metacestode occurs when the temperature rises up to 40 degrees C (i. e.,
      reaching the temperature of the definitive host). Morphogenesis of the uniquely
      large (among the cyclophyllid metacestodes developing in the invertebrate
      intermediate host) metacestode D. asper lasts for about two--three years and is
      associated with the developmental terms of the intermediate host, the larva of
      the Aeshna dragonfly, in climatic conditions of the Far North-East of Asia. Early
      stages of morphogenesis of D. asper were noted at the dragonfly larvae of the age
      of 0+ (at September) and 1+ (at June), and fully-developed metacestodes, only at
      elder ages. Owing to the extremely large size of D. asper metacestodes we refer
      them as a specific modification of cysticercoids: a megalocercus (Megalocercus).
      Common features were noted in the structure and morphogenesis of D. asper
      megalocercus and ascocerci of Schistotaeniidae. High morphological similarity of
      these metacestodes and their development in relative taxonomic groups of
      intermediate hosts, larvae of amphibiotic insects (the dragonfly larvae, and
      occasionally the larvae of mayflies or water-bugs), prove their belonging to the
      same philogenetically related group of metacestodes Cyclophyllidea, emerging
      independently from other groups of cysticercoids. We suggest naming this morpho
      ecological group of larvocysts as ascocerci (or ascocysticercoids). The use of
      the name "ascocercus" as nominal nomenclature for group of larvocysts supposes
      the change of the name "ascocercus Schistotaeniidae" to "euascocercus".

PMID- 23866617
TI  - [Monitoring of the helminth fauna of small rodents of land reclamation canal
      banks in Belorussian Polesie].
AB  - The results of monitoring of the helminth fauna of small rodents dwelling in land
      reclamation canal banks performed in 2005-2010 in Belorussian Polesie are
      presented. A total of 38 helminth species were revealed, and the total
      infestation rate constituted 56.0%. The data are compared with similar
      observations performed in 1996-1999.

PMID- 23866616
TI  - [A case study of singular spectrum analysis application in parasitology: dynamics
      of prevalence of Cryptocotyle concavum and Bunocotyle progenetica trematode
      parthenitae in Hydrobia ventrosa snails at the White Sea].
AB  - In this study parasitological data were analyzed by different methods of
      revealing the structure of time series, namely auto-correlation analysis (ACA),
      Fourier spectrum analysis (SA) and singular spectrum analysis (SSA), and the
      results of these analysis were compared (SSA makes it possible to present non
      stationary time series as a sum of independent components and to determine the
      contribution of each component into the dispersion of the initial series-
      Golyandina et al., 2001). This case study was based on the result of 10-year-long
      monitoring of changes in the prevalence of Cryptocotyle concavum and Bunocotyle
      progenetica trematode parthenitae in intertidal snails Hydrobia ventrosa at the
      White Sea (in total, 45 observations). ACA did not reveal any statistically
      significant oscillations in the analyzed series. The application of SSA and SA
      allowed us to reveal at least two quasi-periodical components. In addition, SSA
      made it possible to reveal a significant dome-shaped trend in the prevalence of
      B. progenetica parthenitae, which were described by SA as an oscillation with a
      period equal to the duration of the study, as well as to give proof that there
      was no trend in the changes of C. concavum parthenitae prevalence. The components
      (modes) extracted by the SSA described the changes in the prevalence better that
      the harmonics extracted by the SA. In particular, SSA modes (contrary to SA
      harmonics) reflected that the amplitude of oscillations of the B. progenetica
      prevalence increased as the prevalence grew. The sums of SSA modes correlated
      more with initial prevalence series that the sums of SA harmonics. A possible
      interpretation of the trends and modes extracted by the SSA in the light of the
      transmission features of the investigated trematode species in the study area was
      proposed.

PMID- 23866618
TI  - [Trematodes of birds (Aves) from the Middle Volga region. 1. Orders
      Brachylaimidae, Cyclocoelida, Echinostomatida, Notocotylida, and Opisthorchiida].
AB  - The data on trematodes of the orders Brachylaimidae, Cyclocoelida,
      Echinostomatida, Notocotylida, and Opisthorchiida from the Middle Volga region
      are given. Records of different authors are supplemented with the results of our
      own research. Reliable records are confirmed for 61 trematode species. The
      following characteristics for each parasite species are given: the systematic
      position, the host spectrum, locality, collecting sites, biology, degree of host
      specificity, and the geographical range. Morphological descriptions and original
      figures of 3 trematodes species are given.

PMID- 23866619
TI  - [Interactions of 1A2 insulator with promoter of hsp 70 gene in Drosophila
      melanogaster].
AB  - Insulators are regulatory DNA elements that participate in the modulation of the
      interactions between enhancers and promoters. Depending on the situation,
      insulators can either stabilize or destroy the contacts between enhancers and
      promoters. A possible explanation for the activity of insulators is their ability
      to directly interact with gene promoters. In the present study, it was
      demonstrated that, in model systems, a 1A2 insulator could interact with the core
      sequence of an hsp70 promoter. In this case, the insulator protein CP190 is found
      on the hsp70 promoter, which depends on the presence of an insulator in the
      transgene. The data obtained are consistent with the model, which implies that
      direct contacts between insulators and promoters make a considerable contribution
      to the modulation of the interactions between insulators and promoters.

PMID- 23866620
TI  - Transformation of LTP gene into Brassica napus to enhance its resistance to
      Sclerotinia sclerotiorum.
AB  - Rapeseed (Brassica napus L.) is one of the most important economic crops
      worldwide, and Sclerotinia sclerotiorum is the most dangerous disease that
      affects its yield greatly. Lipid transfer protein (LTP) has broad-spectrum anti
      bacterial and fungal activities. In this study, B. napus was transformed using
      Agrobacterium tumefaciens harboring the plasmid-containing LTP gene to study its
      possible capability of increasing plant's resistance. First, we optimized the
      petiole genetic transformation system by adjusting the days of explants,
      bacterial concentrations, ratio of hormones, and cultivating condition. Second,
      we obtained 8 positive plants by PCR analysis of T0 generation. The PCR results
      of T1 generation were positive, indicating that the LTP gene had been integrated
      into B. napus. Third, T1 transgenic plants inoculated by detached leaves with
      mycelia of S. sclerotiorum showed better disease resistance than non
      transformants. Oxalic acid belongs to secondary metabolites of S. sclerotiorum,
      and several studies have demonstrated that the resistance of rapeseed to oxalic
      acid is significantly consistent with its resistance to S. sclerotiorum. The
      result from the seed germination assay showed that when T1 seeds were exposed to
      oxalic acid stress, their germination rate was evidently higher than that of non
      transformant seeds. In addition, we measured some physiological changes in T1
      plants and control plants under oxalic acid stress. The results showed that T1
      transgenic plants had lower malondialdehyde (MDA) content, higher super oxide
      dismutase (SOD), and peroxidase (POD) activities than non-transformants, whereas
      disease resistance was related to low MDA content and high SOD and POD
      activities.

PMID- 23866621
TI  - [Factor analysis of interactions between alfalfa nodule bacteria (Sinorhizobium
      meliloti) genes that regulate symbiotic nitrogen fixation].
AB  - Factor analysis has been conducted for the data on the interaction between the
      genes of the root nodule bacteria (rhizobia), which influence the efficiency of
      symbiosis with leguminous plants, including dctA (encoding succinate permease),
      dctBD (activating the dctA gene due to binding its enhancer in the presence of
      succinate), rpoN (activating the promoters of dctA and nitrogenase genes nifHDK),
      and nifA (activating the nitrogenase genes due to binding their enhancers). The
      analysis of the alfalfa rhizobia (Sinorhizobium meliloti) recombinants that
      contain additional copies ofthese genes suggested the antagonistic (epistatic)
      interaction between nifA and rpoN. It may be associated either with the
      competition for C compounds imported into the nodules between the energy
      production and nitrogen assimilation processes or with the competition for redox
      potentials between the oxidative phosphorylation and nitrogen fixation processes.
      Since the phenotypic effects of the studied genes depend on the activity of
      nitrogen export into the aerial parts of plants, we suppose that its accumulation
      in bacteroids impairs the activation of the nifHDK genes by the NifA protein due
      to its interaction with the GlnB protein (the nitrogen metabolism regulator) or
      with the FixLJ and ActSR proteins (the redox potential regulators).

PMID- 23866622
TI  - [Effect of nitrogen source on gene expression of first steps of methanol
      utilization pathway in Pichia pastoris].
AB  - Pichia pastoris is a methylotrophic yeast that is widely used for the expression
      of heterologous proteins. Here, we have investigated the dependence of AOX1 and
      CAT1 expression on the source of nitrogen. It has shown that the expression of
      AOX1 and CAT1 depends on the source of nitrogen. In the presence of a rich
      nitrogen source, such as glutamine or ammonium sulfate, the AOX1 and CAT1
      expression was dramatically induced. With proline as the nitrogen source AOX1 and
      CATI expression was reduced by more than threefold. The expression of these genes
      is controlled at the level of transcription. We have shown the impact of the
      nitrogen source on the growth rate in the presence of methanol as a sole carbon
      source. The specific growth rate was highest on media that contained proline as a
      nitrogen source compared to media with a rich nitrogen source.

PMID- 23866623
TI  - [Morphologic and AFLP analysis of relationships between tulip species Tulipa
      biebersteiniana (Liliaceae)].
AB  - In populations of four species of tulips, (Tulipa biebersteiniana, T. patens, T.
      scytica and T. riparia) from the Volgograd, Kurgansk, Orenburg, and Chelyabinsk
      regions and the Republic of Bashkortostan, genetic diversity was studied by means
      of morphological and AFLP analysis. A morphological analysis of seven
      quantitative and two qualitative criteria was carried out. Three selective
      EcoRI/MseI primer pairs allowed one to genotype 81 individuals from 13 tulip
      populations with 87 loci. The low level of variability by AFLP loci were revealed
      in all species, including T. biebersteiniana (P = 20.41%, UH(e) = 0.075), T.
      patens (26.97%, 0.082), T. scytica (27.53%, 0.086), and T. riparia (27.72%,
      0.096). According to the AMOVA results, the variability proportion that
      characterizes the differences between the four Tulip species was lower (F(CT) =
      0.235) than between populations within species (F(ST) = 0.439). Tulipa patens is
      well differentiated by means of Nei's distances, coordination, and analysis in
      the STRUCTURE program. An analysis in the STRUCTURE revealed four genetic groups
      of tulips that are not completely in accordance with the analyzed species. This
      acknowledges the presence of complicated genetic process in the tulip population.

PMID- 23866624
TI  - [Mapping of meiotic genes in rye (Secale cereale L.): localization of sy18
      mutation with impaired homologous synapsis using microsatellite markers].
AB  - The recessive spontaneous sy18 mutation with nonhomologous synapsis was mapped in
      rye. The sy18 gene was located in the centromeric region of chromosome 2R in
      relation to three rye SSR (simple sequence repeats) loci, i.e., Xrems1130,
      Xrems1203, and Xscm43, and one wheat SSR locus Xgwm132. The desynaptic sy18 gene
      is located in the interval between Xrems1130 and Xrems1203 markers at a distance
      of 0.5 cM and 3.1 cM, respectively. The possible evolutionary relationships of
      the mapped gene with homologous loci of the related species are discussed.

PMID- 23866625
TI  - [Craniometric differences between karyotypic races of the common shrew Sorex
      araneus (Mammalia) as a result of limited hybridization].
AB  - The contact points of four karyotypic races (St. Petersburg, Moscow, Seliger and
      West Dvina) of the common shrew Sorex araneus L. were studied at the Valdai Hills
      (European Russia) in an area unimpeded by geographic barriers. The populations of
      the races are separated by narrow hybrid zones that represent the most complex
      heterozygous hybrid karyotypes. At these points of contact, the morphometric
      differentiation of karyotype races was examined in 12 cranial measurements in 190
      shrews of a known karyotype. A. comparison of the mean values in studied samples
      of immature shrews revealed statistically significant differences and the
      correlation of some measurements in order to describe the level of musculus
      temporalis. It has been proposed that morphometric differences in the karyotypic
      races were preserved and accumulated because of a 50% reduction of the
      frequencies of hybrids. The deviation from the Hardy-Weinberg ration in the
      frequencies of the genotype and haploid sets of chromosomes in the hybrid zones
      can be attributed to a number of fatalities of hybrid embryos or the nonrandom
      mating of karyotypic races. The ethological isolation might arise in the
      evolution of some karyotypic races from the reduced fitness of the hybrids.

PMID- 23866626
TI  - [Genetic diversity of Anser albifrons Scopoli, 1769 and Anser fabalis Latham,
      1787 in the Russian Far East].
AB  - Using RAPD PCR analysis and sequencing of the 5' end segment of the mtDNA control
      region, the genetic diversity and differentiation of Far Eastern populations of
      greater white-fronted goose Anser albifrons Scopoli, 1769 and bean goose Anser
      fabalis Latham, 1787 were examined. Based on RAPD PCR data, the level of gene
      diversity (h) for A. albifrons (0.3634) and A. fabalis (0.3899) was calculated.
      Sequence data showed considerably higher level of inter-population diversity in
      A. fabalis (26.4%), compared to A. albifrons (1.88%). Similarly, the nucleotide
      and haplotype diversity parameters were somewhat higher in A. fabalis (0.01852
      and 0.955). Phylogenetic reconstructions generated using neighbor-joining and
      maximum parsimony algorithms divided each of the examined species into two
      clusters that differ in the number of haplotypes included. These clusters can
      correspond to the subspecies that live in the Far East.

PMID- 23866627
TI  - Single nucleotide polymorphisms in caprine calpastatin gene.
AB  - The calpains and calpastatin (CAST) make up a major cytosolic proteolytic system,
      the calpain-calpastatin system, found in mammalian tissues. The relative levels
      of the components of the calpain-calpastatin system determine the extent of meat
      tenderization during postmortem storage. Calpastatin (CAST) is a protein
      inhibitor of the ubiquitous calcium-dependent proteases-micro-calpain and m
      calpain. Polymorphisms in the bovine, ovine and pig CAST gene have been
      associated with meat tenderness but little is known about how caprine CAST gene
      may affect goat meat quality traits. In this study we selected different parts of
      the CAST gene: 1) that have been previously reported to be polymorphic, intron 5
      and 12 and 3'UTR; 2) first time explored (exon 3, 7 and 8 and part of intron 7
      and 8) to investigate polymorphic status of caprine CAST gene. Using comparative
      sequencing ten novel SN Ps located in exon 3 and intron 5, 7 and 8 were
      identified. Previously reported SNPs in intron 5, 3'UTR and intron 12 were
      absent. Sequence analysis revealed a non synonymous amino acid variation in exon
      3, which would result in Lys/Arg substitution in the corresponding protein
      sequence. Considerable variation was detected in intronic regions. Twenty-four
      InDel were also recognized in intronic regions (15) and 3'UTR (9). All the
      sequences shared high homology with published bovine and ovine sequences. Three
      PCR-RFLP loci have been established for further analyzing genetic polymorphism in
      indigenous goats.

PMID- 23866628
TI  - [Genetic demography of populations of three megalopolises in relation to the
      problem of creating genetic databases].
AB  - Based on data collected from urban residents by questionnaire, the basic
      parameters of the genetic-demographic structure of populations of the three
      megalopolises, i.e., Moscow, Kharkov, and Minsk, have been calculated, including
      the migration coefficients and their dynamics in generations, the radius of the
      cities migration attraction, the parameters of marriage structure (the proportion
      ofinterethnic marriages, the level of intraethnic assortative mating, the marital
      distances), and the gene flow between the ethnic groups. It is shown that the
      representatives of the most numerous ethnic groups in each megalopolis have
      considerable amount of admixture. For Russians of Moscow, Ukrainians of Kharkov,
      and Belarusians of Minsk, the proportion of individuals whose ancestors were all
      born in the given city for at least three generations and belonged to the same
      nationality turned out to be very low (4.75% in Moscow, 1.83% in Kharkov, and
      3.13% in Minsk). This finding questions the formation of a reference population
      in the megalopolis as a sampling of aboriginals of certain ethnic origins. In the
      paper, we justify principles of creating genetic databases for the population of
      the megalopolis taking into account the complexity and dynamism of its population
      structure.

PMID- 23866629
TI  - [Population frequency and age of c.806C > T mutation in CYB5R3 gene as cause of
      recessive congenital methemoglobinemia in Yakutia].
AB  - Type-1recessive congenital methemoglobinemia (RCM) is a rare autosomal disease
      characterized by a deficiency of the soluble form of nicotineamide adenine
      dinucleotide (NADH)-cytochrome b5 reductase (b5R) and clinically manifests as
      cyanosis of skin and mucous membranes. In the Russian Federation, type-I RCM is
      widely disturbed in Yakutia due to the local founder effect. The molecular
      genetics cause of type-I RCM in Yakutia is mutation c.806C > T in the CYB5R3
      gene. In this work we used 13 polymorphic markers, which flanking the CYB5R3 gene
      to establish the founder haplotype. The age of the mutation was estimated as
      about 285 +/- 135 years. In this work, we have evaluated the frequency of the
      c.806 C > T mutation in Yakutia, which averaged 55 : 1000 Yakuts. The calculated
      frequency of disease was 1: 1250 Yakuts.

PMID- 23866630
TI  - [Specialized software product for comparative analysis of multicomponent DNA
      fingerprints].
AB  - "GelAnalyzer" software, which is used to identify and correctly compare DNA
      fingerprints consisting of a large number of discrete bands, has been developed
      by the project to study the quantitative changes in DNA polymorphism patterns in
      animals and humans exposed to gamma radiation. The actual capabilities of this
      program are much broader and include the possibility to analyze the images of any
      multicomponent gels containing fragments of DNA, RNA, and proteins. This software
      product runs on Windows. "GelAnalyzer" allows one to analyze gel images obtained
      by a scanner, camera, or digital camera and ensures the visual control of the
      identification and comparative analysis of bands; it also makes it possible to
      take into account the bands that are poorly identified automatically and exclude
      the artifacts (incidental marks) on images. The operation of "GelAnalyzer"
      software is based on the determination of the values of normalized coordinates of
      bands with allowance for the relative electrophoretic mobility (Rf) of PCR
      products and comparison of their spectra (set of bands in gel lanes) to reveal
      the similarities or differences in their components with subsequent statistical
      data processing and display the results of the analysis.

PMID- 23866631
TI  - [Concordance between vasopressin gene expression and growth of Walker 256
      carcinosarcoma in rats].
AB  - The growth features of Walker 256 carcinosarcoma in rats of different genotypes
      were investigated. The experiments has been carried out on rats of the inbred
      Brattleboro and WAG lines, as well as on their hybrids segregated during congenic
      translocation of the normal vasopressin gene to the genotype of the Brattleboro
      rats. Brattleboro rats do not express the vasopressin gene. It has been found
      that there are only two types of tumor growth dynamics. In rats of the inbred
      Brattleboro line and in homozygotes di/di, that were segregated by backcrossings
      of heterozygous offsprings from the original crossbreeding between (WAG x
      Brattleboro) F1 x Brattleboro and the individuals with parental Brattleboro
      genotype, having grown to some extent the tumor regresses and disappears. In
      hybrid heterozygous siblings of di/+ genotype tumor grows linearly with time and
      always leads to fatal outcome. It has been found that, in the congenic procedure,
      the tumor regression trait is stably maintained and persistently inherited in
      lineage concordantly with the di/di genotype and, in rats with at least one
      allele of a normally expressed vasopressin gene, continuous and lethal tumor
      growth is always observed.

PMID- 23866632
TI  - [Effect of additional disease (comorbidity) on association of allergic rhinitis
      with KCNE4 gene rs12621643 variant].
AB  - Analysis of association of allergic rhinitis with the KCNE4 gene rs12621643
      variant was conducted in Russian residents of Western Siberia (taking into
      account comorbidity with bronchial asthma). It was found that, among individuals
      without bronchial asthma, the frequencies of the KCNE4*G allele and KCNE4*G/G
      genotype are significantly higher in patients with rhinitis compared to
      individuals without it. At the same time, no association of rs12621643 with
      rhinitis was detected in the group of individuals with bronchial asthma. The data
      obtained indicate the association of the KCNE4 gene variability with allergic
      rhinitis, although the effect of this gene relative to the development of the
      disease can be leveled against a background of the manifestation of another
      atopic disease.

PMID- 23866633
TI  - Revised model needs high level buy-in.
AB  - In late January this year the Department of Health (DH) released a revised and
      updated version of its NHS Premises Assurance Model (NHS PAM), a software-based
      tool originally launched in 2010 to enable estates and facilities managers to
      more easily gauge the condition of their built assets, provide premises assurance
      to their management Boards, and assure commissioners that healthcare is being
      delivered in fit-for-purpose buildings. Having, in the March 2013 HEJ, described
      some of the key features and benefits of the latest Model, here, in the first
      half of a two-part article, we report on the morning session of the first in a
      series of IHEEM and DH-organised roundtable discussion events planned for coming
      months to help promote the Model, explain its benefits, and encourage wider, NHS
      take-up. The next HEJ (August 2013) will cover the afternoon's debate.

PMID- 23866634
TI  - How to manage water hygiene successfully.
AB  - According to Alan Hambidge, who has over 22 years' experience in health and
      safety risk management, and is an expert in legionellosis and water hygiene,
      'recent developments and research' have resulted in 'an increase in the Health
      and Safety Executive's expectations' on the standards adopted by healthcare
      organisations in looking after their water systems. In our latest technical
      guidance article, he explores 'some of the developments, pitfalls, and traps,
      that indicate the requirement for improvement in competence'.

PMID- 23866635
TI  - Research uncovers 'unacceptable risks'.
AB  - Dr Melvyn Langford C.Eng, MIMechE, MCIBSE, who worked in the NHS for nearly 40
      years, including as an estates and facilities manager at several NHS Trusts, has
      written several previous HEJ articles on 'systematic failures' in the way
      maintenance of NHS healthcare buildings has been managed, and on what he claims
      is a 'fundamental flaw' within the national guidance for backlog maintenance (see
      HEJ - November 2009, September 2010, and September 2011). Here he outlines the
      conclusions of a recent three-year research project, which he says strongly
      suggest that that the service's continuing use of fixed yearly budgets, and a
      lack of sufficient monitoring, may be resulting in what he dubs 'a catalogue of
      systematic failures within most organisations that are generating risk profiles
      that expose patients, visitors, and staff, to unacceptable levels of risk'.

PMID- 23866636
TI  - A better bedroom to aid recovery.
AB  - With considerable evidence that the quality of the building 'space' within which
      mentally unwell patients are cared for impacts significantly both on speed and
      degree of recovery, the Design in Mental Health Network (DIMHN) has been working
      with the BRE and leading product suppliers over the past 5-6 years to develop a
      'Better Bedroom' for such patients. The first Better Bedroom has now been in situ
      at the Warrington headquarters of specialist window and door manufacturer,
      Britplas, since September, attracting considerable interest. The aim is to
      showcase, within a 'mock-up' bedroom adaptable over time to incorporate emerging
      technologies, some of the latest thinking and features for creating mental
      healthcare inpatient accommodation that is not only comfortable, calming, and
      'non-institutional', but also maximises patient and staff safety. HEJ editor,
      Jonathan Baillie, reports.

PMID- 23866637
TI  - Patients and staff help choose designs.
AB  - A wide selection of Altro flooring and wallcovering products have been used in
      the award-winning Ferndene Children and Young People's Centre in Prudhoe,
      Northumberland, to create a healing environment that, according to the company,
      'is visually stunning, as well as safe, hard-wearing, and hygienic'. HEJ reports.

PMID- 23866638
TI  - Green 'heart' for new community hospital.
AB  - Replacing a healthcare facility first opened in 1908 as a 20-bed cottage
      hospital, the recently opened 'new' Finchley Memorial Hospital in north-west
      London was designed by architects, Murphy Philipps, 'to be at the heart of a
      health campus', surrounded by green space for use by both the hospital itself,
      and the local community. The 28 million pounds hospital, which has achieved a
      BREAAM Excellent rating - with an annual energy target of just 35 GJ/100 m3 set
      by SHINE, the Department of Health-backed learning network for sustainable
      healthcare buildings - has also featured as one of only 20 projects in the RIBA
      Health Buildings Exhibition. HEJ editor, Jonathan Baillie, met with lead
      architect, Marc Levinson, to find out more about the key elements, and the
      thinking, that went into the design.

PMID- 23866639
TI  - Innovation flows at Friville facility.
AB  - The key steps that can be taken to minimise the risk of harmful waterborne
      bacteria such as Legionella and Pseudomonas proliferating widely through water
      systems in healthcare premises were discussed in detail during a recent two-day
      event staged by Delabie, one of Europe's leading water control and sanitary
      equipment suppliers, at the company's Friville headquarters in Picardy, northern
      France. As HEJ editor, Jonathan Baillie, reports, the event, held in an
      impressive training centre close to a sizeable factory that exports products
      ranging from antibacterial taps and showers to grab rails to over 70 countries
      worldwide, also provided the opportunity for sharing of expertise and experience
      between the host personnel and a group of 17 public health engineers from
      throughout England and Scotland, who attended as guests.

PMID- 23866641
TI  - Any questions? People with diabetes and caregivers share their support tips.

PMID- 23866640
TI  - The eyes have it. Regular exams wil ensure your vision makes the grade.

PMID- 23866642
TI  - En Vivo! Radio host connect with listeners and each other.

PMID- 23866644
TI  - Show and tell. People affected by diabetes make their voices heard on Capitol
      Hill.

PMID- 23866643
TI  - Her beloved world.

PMID- 23866645
TI  - Keeping cells alive. Can an old drug type give new life to transplants?

PMID- 23866646
TI  - Obamacare continues to be controversial and CMS proposes Medicare reimbursement
      increases.

PMID- 23866647
TI  - Adaptive challenges in medical practices.
AB  - The purpose of this qualitative grounded theory study was to describe the
      theoretical structures of the strategies used by medical practices to navigate
      adaptive challenges. The process of responding to adaptive challenges in five
      medical practices was studied using a grounded theory approach, collecting data
      from interviews with the organizations' leaders and managers. The leadership of
      these medical practices had successfully navigated adaptive challenges within two
      years of the study. The analysis revealed a model that describes the key elements
      in finding solutions to adaptive challenges. The model was named the Adaptation
      Solution Dynamic, which explains the elements of Rational Tools, Relationship
      Commitment, and Achievement Drive. The findings from the results of this study
      provide a theoretical basis for studying how leaders support identifying
      solutions to adaptive challenges.

PMID- 23866648
TI  - Value-based purchasing and the doctor-patient relationship.
AB  - The Value-Based Purchasing (VBP) program was established by the Secretary of
      Health and Human Services, in accordance with mandates under the Patient
      Protection and Affordable Care Act of 2010. Under the VBP program, the Centers
      for Medicare & Medicaid Services will decrease payments for certain Diagnosis
      Related Group (DRG) payments. Of the approximately 3100 acute care hospitals
      affected by the reductions, which hospitals will be able to recoup some of the
      losses and which ones will be forfeiting the total amount will be decided by
      predetermined performance measures. Seventy percent of the VBP Total Performance
      Score (TPS) will involve the Process of Core Measures, which include quality
      measures of treatment of acute myocardial infarction, heart failure, pneumonia,
      healthcare-associated infections, and surgical care improvement. The remaining
      30% of the TPS will be determined by patient satisfaction. Hospitals will be
      graded according to points awarded for quality achievement, improvement from
      baseline, and consistency.

PMID- 23866649
TI  - QR codes: next level of social media.
AB  - The OR code, which is short for quick response code, system was invented in Japan
      for the auto industry. Its purpose was to track vehicles during manufacture; it
      was designed to allow high-speed component scanning. Now the scanning can be
      easily accomplished via cell phone, making the technology useful and within reach
      of your patients. There are numerous applications for OR codes in the
      contemporary medical practice. This article describes QR codes and how they might
      be applied for marketing and practice management.

PMID- 23866651
TI  - Developing a heart institute: the execution of a strategic plan.
AB  - The Heart Institute at Cincinnati Children's Hospital Medical Center was
      chartered in July 2008 with the purpose of integrating clinical cardiovascular
      medicine with basic science research to foster innovations in care of patients
      with congenital heart problems. The initial administrative steering committee
      included representation from a basic scientist, a cardiologist, and a
      cardiothoracic surgeon and was charged with the development of a strategic plan
      for the evolution of the Institute over a five-year horizon. Using structured
      focus groups and staff interviews, the vision, mission, and goals were identified
      and refined. An integrated implementation plan addressing recruitment,
      capitalization, infrastructure, and market opportunities was created and
      executed. The preliminary results demonstrated clinical outcome improvements,
      increased scientific and academic productivity, and financial sustainability. All
      of the goals identified in the initial planning sequence were achieved within the
      five-year time frame, prompting an early evaluation and revision of the strategic
      plan.

PMID- 23866650
TI  - Addressing disruptive behaviors in the organizational setting: the win-win
      approach.
AB  - Disruptive behaviors can have a significant impact on organizational dynamics and
      work relationships and a profound negative effect on staff and patient
      satisfaction, performance efficiency, and patient outcomes. Despite the growing
      call for action, many organizations still have difficulty in addressing these
      issues in a consistent, effective manner. Presented below is a model that focuses
      on causes and barriers and offers solutions designed to promote a "What's in it
      for me?" win-win approach for improving morale, job satisfaction, and patient
      care.

PMID- 23866652
TI  - The final rule: the final omnibus HIPAA rules.

PMID- 23866653
TI  - Visit length in pediatric primary care: lessons from a pilot study.
AB  - As business drivers create pressure to see more patients in a given period, there
      is no reliable guidance regarding the optimal allocation of resources in
      ambulatory visits. Many pediatric primary clinics set appointment lengths in
      increments of "five minutes." Defining the appointment lengths for potentially
      longer visits by arbitrary increments (e.g., twice the time for an acute visit)
      is a common "experiential" scheme. However, how much additional time is really
      needed if the patient is new to practice or when the visit is arranged for
      preventive services is unknown. Identifying the misallocation of clinic resources
      is fundamental because misallocation reduces access for patients and increases
      practice costs. In this study, using a time-motion approach, we examined the
      characteristics of 372 visits in a pediatric primary care clinic.

PMID- 23866654
TI  - Looking for inside help.

PMID- 23866655
TI  - Commentary: something has to give. the question is, what?
AB  - A large facet joint cyst, the size of a walnut, at L5-S1 resulted in an
      "emergency" laminectomy at Asheville, North Carolina's Mission Hospitals on this
      79-year-old active equestrian and retired healthcare consultant, who more than a
      half-century earlier was formally trained in hospital administration and medical
      economics. While as an inpatient, he reflected broadly about today's healthcare
      expenditures, utilization, and quality, and speculated on possible future
      remedies.

PMID- 23866656
TI  - How to improve the performance of a good medical practice team: twelve
      techniques.
AB  - It is incredibly easy to ignore the medical practice team that is doing a good
      job. However, when we allow good performers to continue as they are, they
      probably won't improve. Their performance may even worsen. This is unfortunate
      because with a little bit of effort and support, good performers can often learn
      to excel. This article offers 12 techniques medical practice managers can use to
      bring their team members from good performance to excellent. It describes how to
      use goal-setting, work assignments, modeling, confidence building, team retreats,
      rewards, incentives, and reinforcement to ratchet up a good medical practice
      team's performance. This article also identifies the signs of medical employee
      mediocrity. It describes why setting higher expectations of your medical practice
      employees will ultimately improve their performance. Finally, this article
      suggests 10 practical and affordable strategies that medical practice managers
      can use to reinforce excellent performance in their good employees.

PMID- 23866657
TI  - Transitional care management services: everything you need to know.
AB  - Tired of providing medical services without reimbursement? Learn how to document
      and code for Transitional Care Management, and start receiving reimbursement for
      services you may have been providing gratis.

PMID- 23866658
TI  - Physicians in transition: practice due diligence.
AB  - The landscape of healthcare is changing rapidly. That landscape is now a business
      model of medicine. That rapid change resulting in a business model is affecting
      physicians professionally and personally. The new business model of medicine has
      led to large healthcare organizations hiring physicians as employees. The role of
      a physician as an employee has many limitations in terms of practice and personal
      autonomy. Employed physicians sign legally binding employment agreements that are
      written by the legal team working for the healthcare organization. Thus
      physicians should practice due diligence before signing the employment agreement.
      "Due diligence" refers to the care a reasonable person should take before
      entering into an agreement with another party. That reasonable person should seek
      expertise to represent his or her interests when searching a balanced agreement
      between the physician and organization.

PMID- 23866659
TI  - Practicing like Thomas Edison.
AB  - For many centuries, medicine has practiced in a vacuum, and the healthcare
      profession has been isolated from other scientific disciplines. Beginning in the
      20th century, doctors and scientists have looked to others for ideas,
      suggestions, innovations, and new technologies. Probably no one in the past
      hundred years has done so much to change the world than Thomas Edison. This
      article will discuss eight principles of Edison and how they may apply to our
      profession and our practices.

PMID- 23866660
TI  - The revenue engine that could: "think you can" by refining the revenue cycle with
      the right people, processes, and tools.
AB  - Many physicians continue to wrestle with an economy-in-recovery and declining
      reimbursements. In this business climate, practices can't afford reimbursement
      process mistakes and inefficiencies; they're simply too expensive. Just a few
      denied surgical claims can cost a practice thousands of dollars. That's the cost
      of the annual electronic health records license or the T1 line. Uncovering any
      and all opportunities to improve the speed and efficiency of getting paid can
      positively contribute to the bottom line. This article reiterates the basics and
      "best" practices for efficient revenue cycle operations. The goal is to have the
      right tasks performed by the right number of people at the right time and with
      the right tools to optimize revenue.

PMID- 23866661
TI  - Computer briefs: Blue Cross, Blue Shield, Blue Button.

PMID- 23866662
TI  - [The international multidisciplinary classification of lung adenocarcinoma from
      IASLC/ATS/ERS and problems in clinical practice].
AB  - The international multidisciplinary classification of lung adenocarcinoma
      sponsored by International Association for the Study of Lung Cancer/American
      Thoracic Society/European Respiratory Society in 2011, addresses the
      classification which is appropriate for resection specimens, small biopsies and
      cytology, respectively for the first time. For resection specimens, new concepts
      are introduced such as adenocarcinoma in situ (AIS) and minimally invasive
      adenocarcinoma (MIA); Invasive adenocarcinomas are recommended to be classified
      by comprehensive histologic pattern. During the clinical practice, pathologists
      and clinicians have some confusions in understanding and application of to the
      new guideline to some extent. This paper will interpret this new guideline,
      discuss and analyze the issues that need to be noticed in clinical application. 

PMID- 23866663
TI  - [Role of autophagy on cobrotoxin induced cell death of A549].
AB  - BACKGROUND: It has been proven that cobrotoxin has anti-tumor effect while its
      role in lung cancer is rarely studied. The aim of this study is to assay the anti
      tumor effect of cobrotoxin in cell line A549, and also to explore its possible
      mechanism related to autophagy and P38-MARK pathway. METHODS: Using MTT method to
      observe the inhibition effect of cobrotoxin on the growth of adenocarcinoma cell
      A549 and human lung fibroblast cell HFL1, as well as on that of A549 pretreated
      with 3-MA and SB203580, which are the inhibitor of autophagy and P38-MARK pathway
      respectively. Cell colony tablet cloning experiment was executed to detect the
      effect of cobrotoxin on colony formation of A549. Determining the protein levels
      of beclin-1, LC3, p38 and pP38 in A549 by Western blot after cells were exposed
      to cobrotoxin, or to cobrotoxin combined with either 3-MA or SB203580. RESULTS:
      All of different concentrations of cobrotoxin inhibited the growth of A549, but
      had no obvious effect on that of HFL1. After treating with 3-MA or SB203580, the
      suppress effect of cobrotoxin on A549 reduced. What's more, different
      concentrations of cobrotoxin all significantly suppressed the colony formation of
      A549. The expression of beclin-1 and pP38 in A549 increased obviously after
      exposure to cobrotoxin, and also the ratio of LC3 II to LC3 I amplified with a
      dose-dependant manner, but P62 decreased. The protein level of beclin-1 and the
      ratio of LC3 II to LC3 I in cells pretreated with 3-MA were reduced, while that
      of p62 was increased. Also, in cells that treated with SB203580 before exposed to
      cobrotoxin, the expression of beclin-1, pP38 and the ratio of of LC3 II to LC3 I
      were reduced, but the expression of P62 increased. CONCLUSIONS: Cobrotoxin can
      suppress the growth of A549 in vitro. And the activating of P38-MARK pathway,
      then upregulating autophagy, was involved in cobrotoxin induced anti-tumor
      process.

PMID- 23866664
TI  - [How to make the choice in the retreatment of EGFR-TKI for advanced NSCLC
      patients who benefited from prior gefitinib therapy: the original drug or
      switching to a second EGFR-TKI?].
AB  - BACKGROUND AND OBJECTIVE: For advanced non-small cell lung cancer (NSCLC)
      patients who benefited from prior epidermal growth factor receptor tyrosine
      kinase inhibitor (EGFR-TKI) therapy, the choice of a second TKI therapy has
      gradually become a new strategy for the treatment. Some investigators recommend
      that the second therapy should be continued with the original TKI; however, other
      investigators recommend the administration of another TKI. The aim of this study
      is to explore which choice is more reasonable. METHODS: In retrospect, patients
      with advanced NSCLC or with postoperative relapse of advanced NSCLC achieved
      complete response (CR), partial response (PR) or stable disease (SD) in prior
      Gefitinib therapy, progression free survival (PFS) >=3 months. They received
      repeated Gefitinib or Erlotinib at an interval of at least one month. The
      analysis was carried out with respect to efficacy and optimal population of the
      two groups. RESULTS: A total of 61 patients were enrolled into the study, 30 in
      Gefitinib group and 31 in Erlotinib group. Baseline characteristics of the two
      groups were comparable. In the comparison between patients treated with Gefitinib
      and with Erlotinib, no statistical differences were seen for response rate (10%
      vs 22.6%, P=0.300,6), disease control rate (60% vs 74.2%, P=0.237,8), median PFS
      (3.0 vs 3.5 months, P=0.494,5), or median OS (8.3 vs 8.5 months, P=0.140,8).
      Multivariate analysis showed that in the initial dose of Gefitinib, PFS>=6 months
      (HR=0.317, 95%CI: 0.102-0.984, P=0.046,9). With an interval >=3 months (HR=0.224,
      95%CI: 0.071-0.713, P=0.011,3) between two doses of TKI, the risk of disease
      progression was reduced; but if with an interval >=3 months (HR=0.262, 95%CI:
      0.097-0.705, P=0.008,0), the risk of death was reduced. CONCLUSIONS: Advanced
      NSCLC patients who benefited from prior Gefitinib therapy can benefit again
      either with the original drug Gefitinib or the alternative drug Erlotinib when a
      second TKI therapy is resumed. Such benefit is related to PFS of initial TKI
      therapy and time interval between two doses of TKI.

PMID- 23866665
TI  - [Meta-analysis of association between E-cadherin promoter methylation and lung
      cancer risk].
AB  - BACKGROUND AND OBJECTIVE: As a member of the cadherin superfamily, E-cadherin
      plays a critical role in the maintenance of cell polarity and integrity. And E
      cadherin was reported to be down-regulated and closely related to tumor
      initiation, invasion and metastasis. There have been a number of studies
      investigating the methylation of E-cadherin promoter in relation to various
      cancers. However, the association between E-cadherin promoter methylation and
      lung cancer risk is controversial. The aim of the present study is to evaluate
      the association of E-cadherin promoter methylation with risk of lung cancer by
      conducting a systematic meta-analysis. METHODS: Relevant studies were identified
      by searches of PubMed/MedLine and EMBASE databases before March 2013. Combined
      odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength
      of the association between E-cadherin promoter methylation and lung cancer risk.
      RESULTS: A total of 1,288 samples from 13 independent studies were included in
      the meta-analysis. Overall, a significant association was observed between E
      cadherin promoter methylation and lung cancer risk (OR=4.04, 95%CI: 2.00-8.13,
      P<0.001). Subgroup analyses by ethnic revealed that lung cancer risk was
      increased for individuals carrying the methylated E-cadherin in Asian and
      Caucasian populations (OR=3.28, 95%CI: 1.20-8.92; OR=5.72, 95%CI: 2.40-13.62).
      CONCLUSIONS: The present meta-analysis indicates that the methylation of E
      cadherin promoter is associated with risk of lung cancer.

PMID- 23866666
TI  - [Correlation between pulmonary function indexes and survival time in patients
      with advanced lung cancer].
AB  - BACKGROUND: To those patients with advanced lung cancer, the ultimate objective
      is to improve the curative effect and quality of life, lung function indexes are
      an important factor. We investigate the change of lung function and the
      relationship between pulmonary function indexs and survival time in patients with
      advanced lung cancer. METHODS: Lung function was detected in 59 cases with lung
      cancer and 63 normal controls. The relationship between pulmonary function indexs
      and survival time was analyzed. RESULTS: There was significant difference in
      ventilation function and diffusing capacity between in lung cancer group and
      control group. Vital capacity (VC), forced expiratory volume in one second
      (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), peak expiratory
      flow% (PEF%), maximal ventilatory volume (MVV) were positively correlated with
      survival time in patients with advanced lung cancer (r=0.29, 0.28, 0.28, 0.27,
      0.26, 0.28, P<0.05), residual volume/total lung capacity was negatively
      correlated with survival time (r=-0.31, P<0.05). CONCLUSIONS: The lung function
      decreases in the patients with lung cancer. VC, FEV1, FVC, PEF, PEF%, MVV,
      residual volume/total lung capacity were correlated with survival time in
      patients with advanced lung cancer. The pulmonary function indexs were important
      marker of prognosis in patients with lung cancer.

PMID- 23866667
TI  - [Clinical observation of icotinib hydrochloride in first-line therapy for
      pulmonary adenocarcinoma].
AB  - BACKGROUND AND OBJECTIVE: It has been proven that icotinib hydrochloride, as a
      molecule targeted drug, can be safely and efficiently used to treat advanced non
      small cell lung cancer (NSCLC) for second-line or third-line. This research was
      aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the
      first-line therapy for pulmonary adenocarcinoma. RESULTS: Among the 56 patients,
      the tumor objective response rate (ORR) and disease control rate (DCR) was 46.4%
      (26/56) and 78.6% (46/56), respectively. Among the 20 patients with EGFR
      analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18), DCR
      was 94.4% (17/18) respectively. The ORR with no history of smoke. EGFR positive
      mutation and appearance of rash were significantly higher than those with smoker,
      wild type EGFR, no information about EGFR and no appearance of rash (P<0.05). The
      most common drug-related adverse events were mild skin rash (28.5%) and diarrhea
      (12%). CONCLUSION: Single agent treatment with icotinib hydrochloride is
      effective and tolerable in first-line therapy for pulmonary adenocarcinoma,
      especially with EGFR mutation.

PMID- 23866668
TI  - [Applications of video-assisted thoracic surgery for the diagnosis and treatment
      of patients with small pulmonary nodules].
AB  - BACKGROUND AND OBJECTIVE: Chest computed tomography (CT), particularly thin-slice
      high resolution CT, has low sensitivity and specificity for detecting pulmonary
      nodules <10 mm in size. This limitation leads to challenges in clinical diagnosis
      and treatment of small pulmonary nodules. This study introduces the use of video
      assisted thoracoscopic surgery (VATS) for the diagnosis and treatment of small
      pulmonary nodules. METHODS: From November 2009 to May 2012, 64 patients with
      small pulmonary nodules without prior preoperative pathologic diagnosis were
      treated by pulmonary wedge resection through VATS. The diagnosis of small
      pulmonary nodules was established from rapid frozen section. The type of
      operation depends on the pathology and the condition of the patients. Twenty
      patients with primary lung cancer were subjected to lobectomy and radical
      resection of the lymph nodes by complete thoracospic lobectomy or video-assisted
      thoracoscopic invasive lobectomy. Pulmonary wedge resection was performed in 44
      patients, among whom 21 have benign nodule, 18 have precancerous lesion, 3 have
      metastatic nodule, and 2 have primary lung cancer for which lobectomy was not
      fit. RESULTS: Confirmative diagnosis is difficult to obtain among patients with
      small pulmonary nodules. VATS is effective in the diagnosis and treatment of
      small pulmonary nodules. With VATS, patients with benign small pulmonary nodules
      can be cured, and patients with primary lung cancer can receive definite
      diagnosis and effective treatment in time. CONCLUSIONS: CT-guided hook-wire
      fixation is useful in precise lesion localization for surgical resection.

PMID- 23866669
TI  - [Prophylactic cranial irradiation for limited-stage small cell lung cancer:
      controversies and advances].

PMID- 23866670
TI  - [Advances on effects of triptolide with non-small cell lung cancer].
AB  - Triptolide can cure a variety kinds of non-small cell lung cancer cell lines. It
      can interfere the cell cycle, active the caspase signaling pathway, inhibit the
      of expression vascular endothelial growth factor (VEGF), inhibit the activation
      of NF-kappaB, and through these ways to promote lung cancer cell death. Now the
      anti-tumor mechanism and effect of triptolide was summarized to provide help for
      scientific research and clinical applications in non-small cell lung cancer. 

PMID- 23866671
TI  - [Advances in diagnosis and treatment of brain metastases from the primary lung
      cancer].
AB  - Lung cancer with brain metastasis was 23% to 65%, and is the most common type in
      brain metastasis tumors with the poor prognosis. At present, diagnosis and
      treatment of brain metastases from lung carcinoma and its molecular mechanism
      have become one hot spot of amount researches. Here, we made a systematic review
      of the progress of the clinical features, diagnosis and treatment of brain
      metastases from lung and its molecular mechanism. 

PMID- 23866672
TI  - [Pulmonary blastoma: long-term tracking report in a case with literature review].

PMID- 23866673
TI  - Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF
      Project I-A: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Ischemic heart disease (IHD) is the most common cause of heart
      failure (HF); however, the role of revascularization in these patients is still
      unclear. Consensus on proper use of cardiac imaging to help determine which
      candidates should be considered for revascularization has been hindered by the
      absence of clinical studies that objectively and prospectively compare the
      prognostic information of each test obtained using both standard and advanced
      imaging. METHODS/DESIGN: This paper describes the design and methods to be used
      in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi
      center trial. The primary objective is to compare the effect of HF imaging
      strategies on the composite clinical endpoint of cardiac death, myocardial
      infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI
      HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging
      strategy algorithms according to the question(s) asked by the physicians (for
      example, Is there ischemia and/or viability?), in agreement with local practices.
      Patients will be randomized to either standard (SPECT, Single photon emission
      computed tomography) imaging modalities for ischemia and/or viability or advanced
      imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission
      tomography (PET). In addition, eligible and consenting patients who could not be
      randomized, but were allocated to standard or advanced imaging based on clinical
      decisions, will be included in a registry. DISCUSSION: AIMI-HF will be the
      largest randomized trial evaluating the role of standard and advanced imaging
      modalities in the management of ischemic cardiomyopathy and heart failure. This
      trial will complement the results of the Surgical Treatment for Ischemic Heart
      Failure (STICH) viability substudy and the PET and Recovery Following
      Revascularization (PARR-2) trial. The results will provide policy makers with
      data to support (or not) further investment in and wider dissemination of
      alternative 'advanced' imaging technologies. TRIAL REGISTRATION: NCT01288560.

PMID- 23866675
TI  - Immature psychological defense mechanisms are associated with greater personal
      importance of junk food, alcohol, and television.
AB  - Immature psychological defense mechanisms are psychological processes that play
      an important role in suppressing emotional awareness and contribute to
      psychopathology. In addition, unhealthy food, television viewing, and alcohol
      consumption can be among the means to escape self-awareness. In contrast,
      engaging in, and responding fully to specifically penile-vaginal intercourse
      (PVI) is associated with indices of better emotional regulation, including less
      use of immature defense mechanisms. There was a lack of research on the
      association of immature defense mechanisms with personal importance of junk food,
      alcohol, television, PVI, and noncoital sex. In an online survey, 334 primarily
      Scottish women completed the Defense Style Questionnaire (DSQ-40), and rated the
      personal importance of junk food, alcohol, television, PVI, and noncoital sex.
      Immature defense mechanisms correlated with importance of junk food, alcohol, and
      television. Importance of PVI correlated with mature defenses, and less use of
      some component immature defenses. Importance of alcohol correlated with
      importance of junk food, television, and noncoital sex. Importance of junk food
      was correlated with importance of television and noncoital sex. The findings are
      discussed in terms of persons with poorer self-regulatory abilities having more
      interest in junk food, television, and alcohol, and less interest in PVI. 

PMID- 23866674
TI  - Endoscopic rendez-vous after damage control surgery in treatment of
      retroperitoneal abscess from perforated duodenal diverticulum: a techinal note
      and literature review.
AB  - INTRODUCTION: The duodenum is the second seat of onset of diverticula after the
      colon. Duodenal diverticulosis is usually asymptomatic, but duodenal perforation
      with abscess may occur. CASE PRESENTATION: Woman, 83 years old, emergency
      hospitalised for generalized abdominal pain. On the abdominal tomography in the
      third portion of the duodenum a herniation and a concomitant full-thickness
      breach of the visceral wall was detected. The patient underwent emergency
      surgery. A surgical toilette of abscess was performed passing through the
      perforated diverticula and the Petzer's tube drainage was placed in the duodenal
      lumen; the duodenostomic Petzer was endoscopically removed 4 months after the
      surgery. DISCUSSION: A review of medical literature was performed and our
      treatment has never been described. CONCLUSION: For the treatment of perforated
      duodenal diverticula a sequential two-stage non resective approach is safe and
      feasible in selected cases.

PMID- 23866676
TI  - The accuracy of general practitioner workforce projections.
AB  - BACKGROUND: Health workforce projections are important instruments to prevent
      imbalances in the health workforce. For both the tenability and further
      development of these projections, it is important to evaluate the accuracy of
      workforce projections. In The Netherlands, health workforce projections have been
      done since 2000 to support health workforce planning. What is the accuracy of the
      techniques of these Dutch general practitioner workforce projections? METHODS: We
      backtested the workforce projection model by comparing the ex-post projected
      number of general practitioners with the observed number of general practitioners
      between 1998 and 2011. Averages of historical data were used for all elements
      except for inflow in training. As the required training inflow is the key result
      of the workforce planning model, and has actually determined past adjustments of
      training inflow, the accuracy of the model was backtested using the observed
      training inflow and not an average of historical data to avoid the interference
      of past policy decisions. The accuracy of projections with different lengths of
      projection horizon and base period (on which the projections are based) was
      tested. RESULTS: The workforce projection model underestimated the number of
      active Dutch general practitioners in most years. The mean absolute percentage
      errors range from 1.9% to 14.9%, with the projections being more accurate in more
      recent years. Furthermore, projections with a shorter projection horizon have a
      higher accuracy than those with a longer horizon. Unexpectedly, projections with
      a shorter base period have a higher accuracy than those with a longer base
      period. CONCLUSIONS: According to the results of the present study, forecasting
      the size of the future workforce did not become more difficult between 1998 and
      2011, as we originally expected. Furthermore, the projections with a short
      projection horizon and a short base period are more accurate than projections
      with a longer projection horizon and base period. We can carefully conclude that
      health workforce projections can be made with data based on relatively short base
      periods, although detailed data are still required to monitor and evaluate the
      health workforce.

PMID- 23866677
TI  - Subglottic MALT lymphoma of the larynx in a patient with rheumatoid arthritis.

PMID- 23866678
TI  - Eosinophilic esophagitis associated with laryngeal papillomatosis in a child.

PMID- 23866679
TI  - Stable isotope ecology of Miocene bovids from Northern Greece and the ape/monkey
      turnover in the Balkans.
AB  - Eurasia was home to a great radiation of hominoid primates during the Miocene.
      All were extinct by the end of the Miocene in Western Eurasia. Here, we
      investigate the hypothesis of climate and vegetation changes at a local scale
      when the cercopithecoid Mesopithecus replaced the hominoid Ouranopithecus along
      the Axios River, Greece. Because they are herbivorous and were much more abundant
      than primates, bovids are preferred to primates to study climate change in the
      Balkans as a cause of hominoid extinction. By measuring carbon stable isotope
      ratios of bovid enamel, we conclude that Ouranopithecus and Mesopithecus both
      evolved in pure C3 environments. However, the large range of delta(13)C values of
      apatite carbonate from bovids combined with their molar microwear and mesowear
      patterns preclude the presence of dense forested landscapes in northern Greece.
      Instead, these bovids evolved in rather open landscapes with abundant grasses in
      the herbaceous layer. Coldest monthly estimated temperatures were below 10
      degrees C and warmest monthly temperatures rose close to or above 20 degrees C
      for the two time intervals. Oxygen isotope compositions of phosphate from bulk
      samples did not show significant differences between sites but did show between
      species variation within each site. Different factors influence oxygen isotope
      composition in this context, including water provenience, feeding ecology, body
      mass, and rate of amelogenesis. We discuss this latter factor in regard to the
      high intra-tooth variations in delta(18)Op reflecting important amplitudes of
      seasonal variations in temperature. These estimations fit with paleobotanical
      data and differ slightly from estimations based on climate models. This study
      found no significant change in climate before and after the extinction of
      Ouranopithecus along the Axios River. However, strong seasonal variations with
      relatively cold winters were indicated, conditions quite usual for extant monkeys
      but unusual for great apes distributed today in inter-tropical regions. 

PMID- 23866680
TI  - Spontaneous tumour shrinkage in 1261 observed patients with sporadic vestibular
      schwannoma.
AB  - OBJECTIVE: To determine the rate of spontaneous tumour shrinkage in a group of
      patients with sporadic vestibular schwannoma managed with a 'wait and scan'
      approach. PATIENTS: All patients with a unilateral cerebello-pontine angle tumour
      resembling a vestibular schwannoma were registered prospectively in a national
      database in Denmark. Patients registered with tumour shrinkage were identified
      and all computed tomography and magnetic resonance imaging scans retrieved, re
      evaluated and related to the clinical data. RESULTS: Of 1261 observed patients,
      48 displayed spontaneous shrinkage (3.81 per cent). Mean absolute shrinkage was
      6.25 mm, equivalent to 52.1 per cent. Absolute shrinkage correlated with tumour
      size and followup period, whereas relative shrinkage was significantly greater
      for tumours which were purely intrameatal at diagnosis. There was no correlation
      between age and the degree of shrinkage. CONCLUSION: Four per cent of sporadic
      vestibular schwannomas shrink spontaneously. These findings substantiate the
      'wait and scan' strategy for tumours with a largest extrameatal diameter of up to
      20 mm.

PMID- 23866681
TI  - Association of objectively measured physical activity with body components in
      European adolescents.
AB  - BACKGROUND: Physical activity (PA) is suggested to contribute to fat loss not
      only through increasing energy expenditure "per se" but also increasing muscle
      mass; therefore, it would be interesting to better understand the specific
      associations of PA with the different body's components such as fat mass and
      muscle mass. The aim of the present study was to examine the association between
      objectively measured PA and indices of fat mass and muscle components
      independently of each other giving, at the same time, gender-specific information
      in a wide cohort of European adolescents. METHODS: A cross-sectional study in a
      school setting was conducted in 2200 (1016 males) adolescents (14.7 +/- 1.2
      years). Weight, height, skinfold thickness, bioimpedance and PA (accelerometry)
      were measured. Indices of fat mass (body mass index, % fat mass, sum of
      skinfolds) and muscular component (assessed as fat-free mass) were calculated.
      Multiple regression analyses were performed adjusting for several confounders
      including fat-free mass and fat mass when possible. RESULTS: Vigorous PA was
      positively associated with height (p<0.05) in males, whilst, vigorous PA,
      moderate-vigorous PA and average PA were negatively associated with all the
      indices of fat mass (all p<0.01) in both genders, except for average PA in
      relation with body mass index in females. Regarding muscular components, vigorous
      PA showed positive associations with fat-free mass and muscle mass (all p<0.05)
      in both genders. Average PA was positively associated with fat-free mass (both
      p<0.05) in males and females. CONCLUSION: The present study suggests that PA,
      especially vigorous PA, is negatively associated with indices of fat mass and
      positively associated with markers of muscle mass, after adjusting for several
      confounders (including indices of fat mass and muscle mass when possible). Future
      studies should focus not only on the classical relationship between PA and fat
      mass, but also on PA and muscular components, analyzing the independent role of
      both with the different PA intensities.

PMID- 23866682
TI  - Consumption of animal source foods and dietary diversity reduce stunting in
      children in Cambodia.
AB  - BACKGROUND: Malnutrition in children is a major public health concern. This study
      aimed to determine the association between dietary diversity and stunting,
      underweight, wasting, and diarrhea and that between consumption of each specific
      food group and these nutritional and health outcomes among children. METHODS: A
      nationally representative household survey of 6209 children aged 12 to 59 months
      was conducted in Cambodia. We examined the consumption of food in the 24 hours
      before the survey and stunting, underweight, wasting, and diarrhea that had
      occurred in the preceding 2 weeks. A food variety score (ranging from 0 to 9) was
      calculated to represent dietary diversity. RESULTS: Stunting was negatively
      associated with dietary diversity (adjusted odd ratios [ORadj] 0.95, 95%
      confident interval [CI] 0.91-0.99, P = 0.01) after adjusting for socioeconomic
      and geographical factors. Consumption of animal source foods was associated with
      reduced risk of stunting (ORadj 0.69, 95% CI 0.54-0.89, P < 0.01) and underweight
      (ORadj 0.74, 95% CI 0.57-0.96, P = 0.03). On the other hand, the higher risk of
      diarrhea was significantly associated with consumption of milk products (ORadj
      1.46, 95% CI 1.10-1.92, P = 0.02) and it was significantly pronounced among
      children from the poorer households (ORadj 1.85, 95% CI 1.17-2.93, P < 0.01).
      CONCLUSIONS: Consumption of a diverse diet was associated with a reduction in
      stunting. In addition to dietary diversity, animal source food was a protective
      factor of stunting and underweight. Consumption of milk products was associated
      with an increase in the risk of diarrhea, particularly among the poorer
      households. Both dietary diversity and specific food types are important
      considerations of dietary recommendation.

PMID- 23866684
TI  - The long-term effects of birthing interventions on childhood empathy.
AB  - OBJECTIVES: birthing practices have changed drastically over the past century. It
      is now more common for women to birth in a hospital, receive drug interventions,
      and to birth via caesarean section, yet there is a paucity of research on long
      term outcomes associated with practices. The research was designed to determine
      if there were any long-term effects of the birthing experience on child empathic
      behaviour. METHODS: two-hundred-and-sixty-four mother-child dyad
      (M(child_age)=5.92 years; SD=.85 years; 127 boys) completed either a
      questionnaire on birthing practices (mothers) or a modified Stickers Task to
      assess empathic behaviour (child). RESULTS: there was a non-significant effect
      (Delta=.22, p=.395) of home versus hospital birth and a small-moderate,
      significant (Delta=.33, p=.017) effect of the use of epidurals during, with
      children of mothers who did not use an epidural or who birthed at home showing
      greater empathic behaviour. CONCLUSIONS: the birthing location and the decision
      to have an epidural can have long-term consequences on children's empathy. While
      researchers need to further examine the mechanisms behind these findings, parents
      should be made aware of the potential long-term effects in order to allow them to
      make fully informed decisions.

PMID- 23866685
TI  - Primiparous and multiparous mothers' perceptions of social support from nursing
      professionals in postnatal wards.
AB  - OBJECTIVE: the study aimed at evaluating primiparous or multiparous mothers'
      perceptions of social support from nursing professionals (SSNP) in postnatal
      wards and factors associated with SSNP. DESIGN: a cross-sectional and
      correlational design was used. METHODS: data was collected in 2007-2008 in two
      maternity hospitals with a convenience sample of Finnish-comprehending
      primiparous and multiparous mothers (N=1300). Multiple-birth and early discharge
      mothers were excluded. The amount of SSNP including affection, affirmation and
      concrete aid was measured. Questionnaires were returned from 754 mothers (58%).
      Fisher's exact test, t-test, Pearson's correlation coefficients, ordinal
      regression and multiple regression were used in the analyses. FINDINGS: mothers
      perceived the amount of SSNP as moderate. The amount of affirmational support was
      perceived as the highest compared with concrete and affectional support.
      Multiparas received statistically significantly less concrete aid compared with
      primiparas. The number of mother- and infant-related factors was substantial and
      their association was stronger among primiparas. Depressive symptoms were a
      significant factor among multiparas. Advice from nursing professionals, parenting
      self-efficacy, mother's age and infant age explained 54.0% of the variation in
      SSNP for primiparas. Correspondingly, advice from nursing professionals, state of
      mind on hospital discharge and family functioning explained 49.3% of the
      variation in SSNP for multiparas. KEY CONCLUSION AND IMPLICATIONS FOR PRACTICE:
      primiparas that are vulnerable for a scarce amount of SSNP were easier to
      recognise on the basis of their background information, infant characteristics,
      childbirth-related factors, and sense of efficacy. Challenges lie in taking into
      account the whole family, especially among multiparas, and in developing
      professionals' guidance skills. Among primiparas the model of postpartum care may
      matter. Our results give professionals a better understanding of the resources
      and challenges faced by mothers in order to develop postnatal SSNP.

PMID- 23866686
TI  - Safe Delivery Posts: an intervention to provide equitable childbirth care
      services to vulnerable groups in Zahedan, Iran.
AB  - BACKGROUND: Recently, there has been a shift towards alternative childbirth
      services to increase access to skilled care during childbirth. OBJECTIVE: This
      study aims to assess the past 10 years of experience of the first Safe Delivery
      Posts (SDPs) established in Zahedan, Iran to determine the number of deliveries
      and the intrapartum transfer rates, and to examine the reasons why women choose
      to give birth at a Safe Delivery Post and not in one of the four large hospitals
      in Zahedan. DESIGN: A mixed-methods research strategy was used for this study. In
      the quantitative phase, an analysis was performed on the existing data that are
      routinely collected in the health-care sector. In the qualitative phase, a
      grounded theory approach was used to collect and analyse narrative data from in
      depth interviews with women who had given birth to their children at the Safe
      Delivery Posts. SETTING: Women were selected from two Safe Delivery Posts in
      Zahedan city in southeast Iran. PARTICIPANTS: Nineteen mothers who had given
      birth in the Safe Delivery Posts were interviewed. FINDINGS: During the 10-year
      period, 22,753 low-risk women gave birth in the Safe Delivery Posts, according to
      the records. Of all the women who were admitted to the Safe Delivery Posts, on
      average 2.1% were transferred to the hospital during labour or the postpartum
      period. Three key categories emerged from the analysis: barriers to hospital use,
      opposition to home birth and finally, reasons for choosing the childbirth care
      provided by the SDPs. KEY CONCLUSION AND IMPLICATIONS FOR PRACTICE: Implementing
      a model of midwifery care that offers the benefits of modern medical care and
      meets the needs of the local population is feasible and sustainable. This model
      of care reduces the cost of giving birth and ensures equitable access to care
      among vulnerable groups in Zahedan.

PMID- 23866687
TI  - Feasibility of pulse oximetry for assessment of infants born in community based
      midwifery care.
AB  - OBJECTIVE: to evaluate the feasibility of using pulse oximetry (PO) for
      evaluating infants born in community-based midwifery care. DESIGN: a prospective,
      observational study of infants born after midwifery supervised (home) births.
      SETTING: 27 midwives from seven practices providing primary care in (home) births
      used PO at birth or the early puerperal period over a ten-month period. Data were
      obtained on the effect of PO on outcome, interventions and decision-making.
      Midwives were surveyed about applicability and usefulness of PO. PARTICIPANTS:
      153 infants born in primary midwifery care. FINDINGS: all births were
      uncomplicated except for one infant receiving supplemental oxygen and another was
      mask ventilated. In 138/153 (90%) infants PO was successfully used and 88% of
      midwives found PO easy to use. In 148/153 (97%) infants PO did not influence
      midwives' clinical judgment and referral policy. In 5/153 (3%) infants, midwives
      were uncertain of the infant's condition, but PO measurements were reassuring. In
      case of suboptimal neonatal condition or resuscitation, 100% of midwives declared
      they would use PO again. KEY CONCLUSIONS: it is feasible to use PO in community
      based midwifery care, but not considered an important contribution to routine
      evaluation of infants. Midwives would like to have PO available during suboptimal
      neonatal condition or when resuscitation is required. IMPLICATIONS FOR PRACTICE:
      PO can be applied in community based midwifery care; it does not lead to
      insecurity or extra referral. Further research on a larger group of infants must
      show the effect of PO on neonatal outcomes.

PMID- 23866683
TI  - Diverse activation of microglia by chemokine (C-C motif) ligand 2 overexpression
      in brain.
AB  - BACKGROUND: The chemokine (C-C motif) ligand 2 (CCL2) is a monocyte
      chemoattractant protein that mediates macrophage recruitment and migration during
      peripheral and central nervous system (CNS) inflammation. METHODS: To determine
      the impact of CCL2 in inflammation in vivo and to elucidate the CCL2-induced
      polarization of activated brain microglia, we delivered CCL2 into the brains of
      wild-type mice via recombinant adeno-associated virus serotype 9 (rAAV-9) driven
      by the chicken beta-actin promoter. We measured microglial activation using
      histological and chemical measurement and recruitment of monocytes using
      histology and flow cytometry. RESULTS: The overexpression of CCL2 in the CNS
      induced significant activation of brain resident microglia. CD45 and major
      histocompatibility complex class II immunoreactivity significantly increased at
      the sites of CCL2 administration. Histological characterization of the microglial
      phenotype revealed the elevation of "classically activated" microglial markers,
      such as calgranulin B and IL-1beta, as well as markers associated with
      "alternative activation" of microglia, including YM1 and arginase 1. The protein
      expression profile in the hippocampus demonstrated markedly increased levels of
      IL-6, GM-CSF and eotaxin (CCL-11) in response to CCL2, but no changes in the
      levels of other cytokines, including TNF-alpha and IFN-gamma. Moreover, real-time
      PCR analysis confirmed increases in mRNA levels of gene transcripts associated
      with neuroinflammation following CCL2 overexpression. Finally, we investigated
      the chemotactic properties of CCL2 in vivo by performing adoptive transfer of
      bone marrow-derived cells (BMDCs) isolated from donor mice that ubiquitously
      expressed green fluorescent protein. Flow cytometry and histological analyses
      indicated that BMDCs extravasated into brain parenchyma and colabeled with
      microglial markers. CONCLUSION: Taken together, our results suggest that CCL2
      strongly activates resident microglia in the brain. Both pro- and anti
      inflammatory activation of microglia were prominent, with no bias toward the M1
      or M2 phenotype in the activated cells. As expected, CCL2 overexpression actively
      recruited circulating monocytes into the CNS. Thus, CCL2 expression in mouse
      brain induces microglial activation and represents an efficient method for
      recruitment of peripheral macrophages.

PMID- 23866689
TI  - Allergic conjunctivitis and the most common allergens in Northern Greece.
AB  - BACKGROUND: Ocular allergies affect a great part of the general population and
      often co exist with other allergic manifestations. In the present study, the
      prevalence of allergic conjunctivitis and the commonest allergens in allergic
      patients at an outpatient unit in Thessaloniki, Greece were evaluated. METHODS:
      This is a retrospective study regarding allergic patients who referred to an
      outpatient clinic between the 1st of January of 1996 and the 31st of December
      2010. They completed relative questionnaires concerning their allergic condition.
      The patients who were included in our study had allergic conjunctivitis confirmed
      by ophthalmologists and were divided into 4 groups. The criteria used were the
      existence of allergic conjunctivitis alone or with other allergic co-
      morbidities. The patients then underwent skin prick tests after consent according
      to current guidelines. RESULTS: The archives of 1239 allergic patients were
      evaluated and 497 patients (40,11%) who manifested eye allergic symptoms were
      included in our study. 448 patients (90.14%) had allergic conjunctivitis in
      conjunction with asthma or rhinitis or both. 370 patients underwent skin prick
      tests and 284 of them (124 males-160 females) were positive for at least 1 of the
      8 tested allergens (76.75%). 166 were positive to a grass mix (58.45%), 130 to
      olea European (45.77%), 124 to dust mites mix (43.66%), 58 to cypress (20.42%),
      71 to parietaria officinalis (25.00%), 67 to cat dander (23.59%), 35 to dog
      dander (12.32%) and 32 to Altenaria (11.26%). CONCLUSIONS: Symptoms of ocular
      allergy are very common in patients with allergic rhinitis and asthma. Men had
      slightly higher percentages of positive skin prick tests, except for dog dander
      and Altenaria. Conjunctivitis should not be overlooked as an allergic entity when
      evaluating allergic patients.

PMID- 23866688
TI  - Rat mesenchymal stem cell secretome promotes elastogenesis and facilitates
      recovery from simulated childbirth injury.
AB  - Vaginal delivery is a risk factor for stress urinary incontinence (SUI).
      Mesenchymal stem cells (MSCs) home to injured organs and can facilitate repair.
      The goal of this study was to determine if MSCs home to pelvic organs after
      simulated childbirth injury and facilitate recovery from SUI via paracrine
      factors. Three experiments were performed. Eighteen female rats received vaginal
      distension (VD) or sham VD and labeled intravenous (IV) MSCs to investigate if
      MSCs home to the pelvic organs. Whole-organ imaging and immunofluorescence were
      performed 1 week later. Thirty-four female rats received VD and IV MSCs, VD and
      IV saline, or sham VD and IV saline to investigate if MSCs accelerate recovery of
      continence. Twenty-nine female rats received VD and periurethral concentrated
      conditioned media (CCM), VD and periurethral control media, or sham VD and
      periurethral control media to investigate if factors secreted by MSCs accelerate
      recovery from VD. Urethral histology and function were assessed 1 week later.
      Significantly more MSCs were observed in the urethra, vagina, and spleen after VD
      compared to sham VD. Continence as measured by leak point pressure (LPP) was
      significantly reduced after VD in rats treated with saline or control media
      compared to sham VD but not in those given MSCs or CCM. External urethral
      sphincter (EUS) function as measured by electromyography (EMG) was not improved
      with MSCs or CCM. Rats treated with MSCs or CCM demonstrated an increase in
      elastin fibers near the EUS and urethral smooth muscle more similar to that of
      sham-injured animals than rats treated with saline or control media. MSCs homed
      to the urethra and vagina and facilitated recovery of continence most likely via
      secretion of paracrine factors. Both MSCs and CCM have promise as novel
      noninvasive therapies for SUI. 

PMID- 23866690
TI  - Saturated fatty acid palmitate-induced insulin resistance is accompanied with
      myotube loss and the impaired expression of health benefit myokine genes in C2C12
      myotubes.
AB  - BACKGROUND: Excessive circular fatty acid, particlarly saturated fatty acid, can
      result in insulin resistance in skeletal muscle, but other adverse effects of
      fatty acid accumulation in myocytes remain unclear. METHODS: Differentiated C2C12
      myotubes were used. The effects of palmitate on cell viability, glucose uptake,
      gene expression and myotube loss were evaluated by MTT assay, 2NBDG uptake, qRT
      PCR, Western Blot and crystal staining-based myotube counting, respectively. In
      some expreiments, oleate was administrated, or the inhibitors of signaling
      pathways were applied. RESULTS: Palmitate-induced cellular insulin resistance was
      clarified by the reduced Akt phosphorylation, glucose uptake and Glut4
      expression. Palmitate-caused myotube loss was clearly observed under microscope
      and proved by myotube counting and expression analysis of myotube marker genes.
      Moreover, palmitate-induced transcriptional suppression of three health benefit
      myokine genes (FNDC5, CTRP15 and FGF21) was found, and the different involvement
      of p38 and PI3K in the transcription of these genes was noticed. CONCLUSIONS:
      Palmitate-induced insulin resistance accompanys myotube loss and the impaired
      expression of FNDC5, CTRP15 and FGF21genes in C2C12 myotubes. These results
      provide novel evidence indicating the negative role of high concentration of
      palmitate in myotubes.

PMID- 23866692
TI  - The role of Clinical Officers in the Kenyan health system: a question of
      perspective.
AB  - BACKGROUND: Despite the increasing interest in using non-physician clinicians in
      many low-income countries, little is known about the roles they play in typical
      health system settings. Prior research has concentrated on evaluating their
      technical competencies compared to those of doctors. This work explored
      perceptions of the roles of Kenyan non-physician clinicians (Clinical Officers
      (COs). METHODS: Qualitative methods including in-depth interviews (with COs,
      nurses, doctors, hospital management, and policymakers, among others),
      participant observation and document analysis were used. A nomothetic-idiographic
      framework was used to examine tensions between institutions and individuals
      within them. A comparative approach was used to examine institutional versus
      individual notions of CO roles, how these roles play out in government and faith
      based hospital (FBH) settings as well as differences arising from three specific
      work settings for COs within hospitals. RESULTS: The main finding was the
      discrepancy between policy documents that outline a broad role for COs that
      covers both technical and managerial roles, while respondents articulated a
      narrow technical role that focused on patient care and management. Respondents
      described a variety of images of COs, ranging from 'filter' to 'primary
      healthcare physician', when asked about CO roles. COs argued for a defined role
      associated with primary healthcare, feeling constrained by their technical role.
      FBH settings were found to additionally clarify CO roles when compared with
      public hospitals. Tensions between formal prescriptions of CO roles and actual
      practice were reported and coalesced around lack of recognition over COs work,
      role conflict among specialist COs, and role ambiguity. CONCLUSIONS: Even though
      COs are important service providers their role is not clearly understood, which
      has resulted in role conflict. It is suggested that their role be redefined,
      moving from that of 'substitute clinician' to professional 'primary care
      clinician', with this being supported by the health system.

PMID- 23866691
TI  - Bee venom effects on ubiquitin proteasome system in hSOD1(G85R)-expressing NSC34
      motor neuron cells.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      that results from a progressive loss of motor neurons. Familial ALS (fALS) is
      caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that
      frequently result in the accumulation of mutant protein aggregates that are
      associated with impairments in the ubiquitin-proteasome system (UPS). UPS
      impairment has been implicated in many neurological disorders. Bee venom (BV)
      extracted from honey bees has been used as a traditional medicine for treating
      inflammatory diseases and has been shown to attenuate the neuroinflammatory
      events that occur in a symptomatic ALS animal model. METHODS: NSC34 cells were
      transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then
      stimulated with 2.5 MUg/ml BV for 24 hrs. To determine whether a SOD1 mutation
      affects UPS function in NSC34 cells, we examined proteasome activity and
      performed western blotting and immunofluorescence using specific antibodies, such
      as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15
      antibodies. RESULTS: We found that GFP-hSOD1G85R overexpression induced SOD1
      inclusions and reduced proteasome activity compared with the overexpression of
      GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV
      treatment restored proteasome activity and reduced the accumulation of
      ubiquitinated and misfolded SOD1 in GFP-hSOD1G85R-overexpressing NSC34 motor
      neuronal cells. However, BV treatment did not activate the autophagic pathway in
      these cells. CONCLUSION: Our findings suggest that BV may rescue the impairment
      of the UPS in ALS models.

PMID- 23866693
TI  - Show me the pragmatic contribution: a developmental investigation of contrastive
      inference.
AB  - An utterance such as 'Show me the large rabbit' potentially generates a
      contrastive inference, i.e., the article the and the adjective large allow
      listeners to pragmatically infer the existence of other entities having the same
      noun (e.g. a small rabbit). The primary way to measure children's ability to
      carry out this pragmatic inference has been through tasks that measure infelicity
      detection. We argue that such studies are not as revealing as one might assume
      because they force children to adopt a metalinguistic stance and they consider
      infelicity detection as tantamount to contrastive inference-making. To address
      these concerns, we develop a game-like situation in which all utterances remain
      felicitous. Moreover, we make a distinction between responses that are revealing
      of a pragmatic interpretation and responses that are revealing of a reliance on
      the utterance's linguistically encoded meaning (i.e., a lack of contrastive
      inference). Three experiments with seven-year-olds, ten-year-olds, and adults
      show that pragmatic interpretations do not emerge among seven-year-olds, that ten
      year-olds do not show adult-like performance, and that adults are not at ceiling.
      We conclude that contrastive inference-making is an effortful process and that
      the ability to detect such gains-in-information through language increases with
      age.

PMID- 23866694
TI  - Effect of a high bicarbonate mineral water on fasting and postprandial lipemia in
      moderately hypercholesterolemic subjects: a pilot study.
AB  - BACKGROUND: During postprandial state, TG concentration is increasing and HDL
      cholesterol decreasing, leading to a transitory pro-atherosclerotic profile.
      Previous studies have reported that bicarbonate water improve postprandial
      lipemia. The objective of this study was to analyze the effect of a strongly
      bicarbonated mineral water on lipoprotein levels during fasting and postprandial
      state. METHODS: A controlled, randomised, double-blind cross-over design was
      conducted in 12 moderately hypercholesterolemic subjects after a daily ingestion
      of 1.25 L of mineral (SY) or low mineral water during eight weeks separated by a
      one week wash-out period. Blood samples were collected in first visit to the
      hospital (V1) before water consumption (referent or SY) and in a second visit
      (V2) after eight week water consumption period. The effect of the consumed water
      was studied in fasting and in postprandial state during ingestion of a meal and
      0.5 L of water. RESULTS: Comparison of data between V1 and V2 after SY
      consumption showed a significant decrease in triglyceridemia (23%), VLDL TG (31%)
      and tendency to a decrease of VLDL cholesterol (p = 0.066) at fasting state.
      Whatever the consumed water during postprandial state, the measurement of total
      areas under curves did not show a significant difference. No difference was
      observed between SY and referent water consumption for measured parameters at
      fasting and postprandial state. CONCLUSION: When subjects consumed SY we showed a
      decrease of their basal TG and VLDLTG. The unexpected absence of effect of high
      mineralized water on postprandial lipemia, probably related to experimental
      conditions, is discussed in the discussion section.

PMID- 23866696
TI  - [Pay attention to history inquiry and clinical examination in diagnosis of
      uveitis].
AB  - Diagnosis of uveitis based on etiologies and entities is essential for the
      treatment of the uveitis patients. A careful and meticulous inquiry about history
      may provide important clue to the diagnosis. Careful and detailed clinical ocular
      examinations allow us to make a correct diagnosis in most uveitis patients.
      Auxiliary examinations and laboratory examinations chosen principally based on
      clinical manifestation enable us to make a definite diagnosis in almost all the
      uveitis patients. 

PMID- 23866695
TI  - Spatiotemporal mathematical modelling of mutations of the dhps gene in African
      Plasmodium falciparum.
AB  - BACKGROUND: Plasmodium falciparum has repeatedly evolved resistance to first-line
      anti-malarial drugs, thwarting efforts to control and eliminate the disease and
      in some period of time this contributed largely to an increase in mortality. Here
      a mathematical model was developed to map the spatiotemporal trends in the
      distribution of mutations in the P. falciparum dihydropteroate synthetase (dhps)
      gene that confer resistance to the anti-malarial sulphadoxine, and are a useful
      marker for the combination of alleles in dhfr and dhps that is highly correlated
      with resistance to sulphadoxine-pyrimethamine (SP). The aim of this study was to
      present a proof of concept for spatiotemporal modelling of trends in anti
      malarial drug resistance that can be applied to monitor trends in resistance to
      components of artemisinin combination therapy (ACT) or other anti-malarials, as
      they emerge or spread. METHODS: Prevalence measurements of single nucleotide
      polymorphisms in three codon positions of the dihydropteroate synthetase (dhps)
      gene from published studies of dhps mutations across Africa were used. A model
      based geostatistics approach was adopted to create predictive surfaces of the
      dhps540E mutation over the spatial domain of sub-Saharan Africa from 1990-2010.
      The statistical model was implemented within a Bayesian framework and hence
      quantified the associated uncertainty of the prediction of the prevalence of the
      dhps540E mutation in sub-Saharan Africa. CONCLUSIONS: The maps presented
      visualize the changing prevalence of the dhps540E mutation in sub-Saharan Africa.
      These allow prediction of space-time trends in the parasite resistance to SP, and
      provide probability distributions of resistance prevalence in places where no
      data are available as well as insight on the spread of resistance in a way that
      the data alone do not allow. The results of this work will be extended to design
      optimal sampling strategies for the future molecular surveillance of resistance,
      providing a proof of concept for similar techniques to design optimal strategies
      to monitor resistance to ACT.

PMID- 23866697
TI  - [Think highly of the diagnose and therapy of ocular pathological changes in the
      HIV infected and AIDS patients].
AB  - Acquired immune deficiency syndrome (AIDS) is a kind of fatal disease which
      involve multiple organs and the public health of global intention. The incidence
      rate in China is escalating obviously. Currently there is lack of large samples
      and long-term systematic observations of ocular pathological changes in the human
      immunodeficiency virus (HIV) infected and AIDS patients. Diagnostic errors and
      missed diagnosis still exist in hospitals, even in some advanced hospitals. They
      delay the therapy of patients, also easily result in hospital acquired
      infections. It is notable that there is insufficient attention to preoperative
      test of anti-HIV in some hospitals, especially in outpatient surgeries. Therefore
      potential iatrogenic infection risks are hidden. Some clinical doctors are afraid
      of AIDS patients, therefore they are lack of subjective initiative to
      comprehensively examination and treatment the patients. For the past few years,
      highly active antiretroviral therapy is widely used, AIDS related morbidity and
      mortality is significantly reduced, and the prevalence rate of ocular
      complications decreased from 55% to 95%. But due to the HIV/AIDS patient volume
      increased year by year, and the survival rate raised, prolonged survival, results
      in the increase of the absolute number of patients with ocular complications.
      Therefore it is critical to pay attention to the HIV/AIDS ocular lesions in the
      diagnosis and treatment of iatrogenic infection. 

PMID- 23866698
TI  - [Pay attention to the standardization of uveitis nomenclature].
AB  - Uveitis is multiple disease entities with complicated causes and various
      manifestations. To better understand and compare the severity and improve multi
      centers clinical research, standardized nomenclature and grade is needed. Based
      on the result of Standardization of Uveitis Nomenclature working group, this
      paper briefly introduce the classification, onset and course, inflammation
      grading, diagnosis standard for complications. 

PMID- 23866700
TI  - [Factors associated with visual prognosis of acute retinal necrosis syndrome].
AB  - OBJECTIVE: To investigate relevant factors affecting the prognosis of acute
      retinal necrosis syndrome (ARN). METHODS: Case-series study. The clinical data of
      41 patients (53 eyes) with ARN were retrospectively analyzed. Eyes were divided
      into two groups according to best corrected visual acuity at final visit. The
      groups were best corrected visual acuity better than 0.1 (group A, 28 eyes) and
      worse than 0.1 (group B, 25 eyes). Data were analyzed using the chi(2) test,
      Fisher exact test, Mann-Whitney test, bivariate correlation statistics, and
      multinomial logistic regression analysis. RESULTS: All patients were treated with
      systemic antivirus drugs and glucocorticoid. Ten eyes were treated with
      prophylactic laser retinopexy, 26 eyes underwent intravitreal ganciclovir, and 31
      eyes underwent vitrectomy. All contralateral eyes of unilateral ARN patients were
      not involved after systemic antivirus treatment. Compared to group B (16.0%,
      4/25), more eyes with best corrected visual acuity better than 0.1 at first visit
      were observed in group A (85.7%, 24/28) (chi(2) = 23.037, P = 0.000). Duration
      from onset of symptoms until first administration of antivirus drugs was shorter
      in group A [(15 +/- 13) days] than in group B [(30 +/- 34) days, Z = -2.414, P =
      0.016]. Compared to group A (25.0%, 7/28; 10.7%, 3/28; 7.1%, 2/28; 39.3%, 11/28),
      more eyes in group B suffered from retinal detachment (80.0%, 20/25), occlusive
      central retinal vasculopathy (56.0%, 14/25), optic atrophy (36.0%, 9/25) and
      proliferative vitreoretinopathy (92.0%, 23/25) (chi(2) = 13.862, 10.440, 5.048,
      13.749; P = 0.000, 0.001, 0.025, 0.000). Logistics regression analysis showed
      that visual prognosis were related to factors including best corrected visual
      acuity better at first visit (OR = 27.225, P = 0.003) and occlusive central
      retinal vasculopathy (OR = 0.065, P = 0.053). No difference in the number of eyes
      with increased intraocular pressure was observed between group A and group B (P >
      0.05). Prophylactic laser retinopexy before retinal detachment and intravitreal
      ganciclovir were not associated with visual prognosis (P > 0.05). CONCLUSION:
      Worse visual acuity at first visit and occlusive central retinal vasculopathy are
      major relevant factors threatening visual prognosis.

PMID- 23866699
TI  - [Clinical observation of 85 patients with Behcet's uveitis treated with
      immunosuppressive agents combined with steroids].
AB  - OBJECTIVE: To investigate the effect and safety of immunosuppressive treatment
      (IMT) combined with steroids in patients with Behcet's uveitis. METHODS: Case
      series study. Eighty-five patients (167 eyes) were enrolled in this study from
      June 2010 to June 2011 at the Beijing Tongren Hospital. The patients were
      examined before the initiation of IMT and were followed up once every 3 months
      after the therapy. The corrected visual acuity, inflammation score, ocular
      complications and side effects of IMT and steroid use were recorded. The rate of
      positive outcomes was reported in person years (PY) or eye years (EY). The
      intervals between the episodes of ocular inflammation were analyzed using Kaplan
      Meier survival analysis. The difference of the proportion of stable cases before
      and after treatment was analyzed by Log-rank test. RESULTS: There were 67 males
      and 18 females. The mean age of diagnosis with Behcet's disease was (30.4 +/-
      9.5) years. The total follow-up period was 255.5 EY and 129.67 PY. The
      percentages of eyes with inflammation that had been stable for at least 3 months
      (91.6%, 153/167) or more than 1 year (22.3%, 37/167) after treatment were
      significantly higher than those before treatment [34.7% (58/167) and 1.0%
      (2/167), respectively] (chi(2) = 137.80, P < 0.01). The incident rate of a
      decrease in visual acuity was 0.11 per EY, and the incident rate of an increased
      in visual acuity was 0.22 per EY. The incident rates of cataracts, an intraocular
      pressure greater than 30 mm Hg (1 mm Hg = 0.133 kPa) or a severe vitreous haze
      were 0.39 per EY, 0.07 per EY and 0.79 per EY, respectively. The incident rates
      of obesity, osteoporosis and hypertension caused by steroid use were 0.4 per PY,
      0.22 per PY and 0.13 per PY, respectively. The common side effects of IMT were
      reversible leukopenia (0.26 per PY by chlorambucil and 0.46 per PY by
      methotrexate), hepatotoxicity (0.21 per PY by cyclophosphamide, 0.13 per PY by
      azathioprine), hematuria (0.21 per PY by cyclophosphamide) and gum hyperplasia
      caused by cyclosporine (0.15 per PY). CONCLUSIONS: Although the use of IMT
      combined with steroids is effective for the control of intraocular inflammation
      in patients with Behcet's uveitis, the occurrence of complications is still high,
      and the vision prognosis is poor. We should pay attention to the side effects of
      the long-term use of steroids, such as hypertension, obesity and osteoporosis.
      The initiation of IMT is recommended over the long-term administration of large
      doses of steroids. The side effects of IMT should be monitored.

PMID- 23866701
TI  - [Clinical research of anterior chamber inflammation after phacoemulsification
      surgery in patients with complicated cataract secondary to uveitis].
AB  - OBJECTIVE: To investigate anterior chamber inflammation after phacoemulsification
      with intraocular lens (IOL) implantation in patients with Vogt-Koyanagi-Harada
      (VKH) syndrome or Behcet's disease (BD). METHODS: Cohort study. Seventeen
      patients (20 eyes) with complicated cataracts and VKH syndrome or BD who
      underwent phacoemulsification with IOL implantation at Zhongshan Ophthalmic
      Center, Sun Yat-Sen University (SYSU) between January 2010 and June 2011 were
      included as the experimental group in this study. Cataract surgery was performed
      on these patients only when uveitis had been under control for more than three
      months. Thirty patients (40 eyes) with age-related cataracts who underwent
      phacoemulsification with IOL implantation in the same period were included as the
      control group. Quantitative measurements of anterior chamber aqueous flare and
      inflammatory cells were conducted preoperatively and postoperatively using a
      Laser Flare Cell Meter (LFCM). Independent t-test was used to compare patients'
      ages, and the energy and time of phacoemulsification between the two groups. The
      Student's t-test was used to assess the differences between paired data
      preoperatively and postoperatively. Independent t-test was also used to assess
      the quantitative data between groups. RESULTS: The study recruited 20 eyes in the
      experimental group and 40 eyes in the control group, including 11 eyes from 9 VKH
      patients and 9 eyes from 8 BD patients. The preoperative and postoperative flare
      values in the experimental group were (19.86 +/- 6.47), (44.28 +/- 18.47), (35.60
      +/- 12.65), (23.85 +/- 8.41), and (13.86 +/- 4.27) pc/ms, respectively, which
      were statistically higher than that of the control group preoperatively, and on
      days 1, 7, 30, and 90 after surgery (tpre = 4.643, Ppre < 0.01; t1 = 6.035, P1 <
      0.01; t7 = 3.595, P7 = 0.001; t30 = 4.658, P30 < 0.01; t90 = 3.308, P90 = 0.002).
      Aqueous flare in Group A and Group B declined to preoperative levels on day 30 (t
      = 0.320, P = 0.753) and day 7 (t = 0.454, P = 0.653). For the experimental group,
      the inflammatory cell count on day 1 and 7 was (83.46 +/- 27.08) and (27.56 +/-
      8.32) cells/0.5 mm(3), respectively, which was significantly higher than the
      preoperative level [(6.47 +/- 3.56)cells/ 0.5 mm(3), t1 = 5.261, P1 < 0.01; t7 =
      2.766, P7 = 0.012]. On days 30 and 90, the inflammatory cell count was (11.43 +/-
      4.81) and (4.82 +/- 2.29) cells/0.5 mm(3), respectively, and there was no
      statistically significant difference in the inflammatory cell count compared with
      the preoperative level (t30 = 2.348, P30 = 0.042; t90 = 1.376, P90 = 0.186). For
      the control group, inflammatory cell count reduced to pre-operative level on day
      7 (t7 = 2.464, P7 = 0.018). CONCLUSIONS: Anterior chamber inflammation reaches
      peak levels one week postoperatively in VKH and BD patients who receive
      phacoemulsification with IOL implantation. It takes three months for the
      inflammation to recede, and might take longer for complete restoration of the
      blood-aqueous barrier.

PMID- 23866702
TI  - [Screening of key genes and inflammatory signalling pathway involved in the
      pathogenesis of HLA-B27-associated acute anterior uveitis by gene expression
      microarray].
AB  - OBJECTIVE: To investigate the genes and signalling pathways located upstream of
      the inflammatory processes in human leukocyte antigen (HLA)-B27-associated acute
      anterior uveitis by gene expression microarray. METHODS: Experimental study. HLA
      B27-positive and-negative monocytes isolated from human peripheral blood were
      stimulated with Vibrio cholera lipopolysaccharide (LPS). Gene expression
      microarrays were used to identify the differentially expressed genes.
      Differentially expressed (DE) genes were testified by real-time PCR and analyzed
      by a series of bioinformatics-based techniques such as Gene Ontology, Kyoto
      Encyclopedia of Genes and Genomes. RESULTS: Gene expression microarray analysis
      revealed marked differences between HLA-B27-positive acute anterior uveitis (AAU)
      and HLA-B27-negative healthy control peripheral monocytes in the genes that were
      upregulated in response to LPS stimulation with 1105 genes and 25 genes
      respectively. Gene Ontology enrichment and pathway analysis indicated that genes
      participating in protein transport and folding were essential to the inflammatory
      process. The LPS receptor-Toll-like receptor (TLR)4 induced TLR signalling
      pathway and pathway related to Vibrio cholerae infection were located upstream of
      the network and contribute to the overall response. Among the DE genes, PIK3CA,
      PIK3CB, AKT3, and MAPK1 might play critical roles in inflammation. CONCLUSIONS:
      Equivalent LPS stimulation induces a different response in HLA-B27-positive
      peripheral monocytes compared to normal control, suggesting that the TLR pathway
      is involved in the pathogenesis of HLA-B27-associated AAU.

PMID- 23866703
TI  - [Effects of exogenous interleukin-2, interleukin-23 on differentiation of IRBP 1
      20-specific T cells toward Th1 and Th17 and comparison of the pathogenicity of
      IRBP 1-20-specific T cells].
AB  - OBJECTIVES: To explore the effects of exogenous interleukin (IL)-2 and IL-23 on
      differentiation of IRBP 1-20-specific T cells originated from C57BL/6 mouse with
      experimental autoimmune uveitis (EAU) and to investigate the difference in
      pathogenicity. METHODS: Experimental study. Thirty C57BL/6 mice were immunized
      subcutaneously with 200 ul emulsion containing 200 ug interphotoreceptor retinoid
      binding protein (IRBP) 1-20 and 0.8 mg mycobacterium tuberculosis in complete
      Freund's adjuvant, distributed over six spots at the tail base and on the flank.
      On postimmunization Day 13, spleens and draining lymph nodes were removed from
      mice, and a part of spleens, as the control group, was reserved for examining the
      expression of IFN-gamma mRNA and IL-17 mRNA by RT-PCR. T cells were isolated from
      the rest of spleens and lymph nodes by passage through a nylon wool column, and
      then T cells were stimulated for 48 hours with IRBP 1-20 in the presence of
      antigen-presenting cell and mouse recombinant cytokine IL-2 or IL-23. The IRBP 1
      20-specific T cells were separated by Ficoll gradient centrifugation, the
      expressions of IFN-gamma mRNA and IL-17 mRNA were assessed by RT-PCR, and IFN
      gamma and IL-17 in T cells supernatant were detected using a commercial ELISA
      kit. The T cells were cultured for another 48 hours, and then the proportions of
      IL-17(+)gammadelta(+)T cells were analyzed by flow cytometry. EAU models were
      built in 30 C57BL/6 mice, T cells from which were randomly divided into two
      groups according to the methods mentioned above: IL-2 group and IL-23 group.
      Transfer EAU models were built in other 6 mice and divided into two groups, IL-2
      group and IL-23 group, by intraperitoneal injection of 3.5*10(6) IRBP-special-T
      cells from IL-2 group or IL-23 group respectively. Clinical changes were observed
      by indirect ophthalmoscopy on postimmunization day 3, 7, 14. For
      histopathological evaluation, whole eyes were collected on postimmunization day
      21. Rank sum test, one-way ANOVA and paired t test were used to analyze the
      results. A comparison of pathogenicity was made between Th1 and Th17 through
      clinical observation and histopathological evaluation of B6 mouse. RESULTS:
      Rosette formation was found among T cells on poststimulation day 2. There was a
      statistical difference in the expression of IFN-gamma mRNA between the IL-2 group
      and normal group or IL-23 group (0.26 +/- 0.02 vs. 0.12 +/- 0.05 or 0.10 +/-
      0.00) (F = 80.51, P = 0.003); however, the expression of IFN-gamma in the IL-2
      group [(13 124.67 +/- 107.73) ug/L] was higher than that of the IL-23 group
      [(3953.67 +/- 117.34) ug/L] (t = 169.61, P = 0.000); and the expression of IL-17
      mRNA in the IL-2 group [(588.67 +/- 77.43) ug/L] was lower than that of the IL-23
      group [(5038.33 +/- 88.00) ug/L] (t = -361.71, P = 0.000). Flow cytometer showed
      that the concentration of IL-17 in the IL-2 group [(3.23 +/- 0.28)%] was
      significantly lower than that in the IL-23 group [(9.93 +/- 0.55)%] (t = -33.18,
      P = 0.001). There was a significant difference in the proportion of IL
      17(+)gammadelta(+)T cells between the IL-23 group and IL-2 group (9.93 +/- 0.55
      vs. 3.23 +/- 0.28) (t = -33.18, P = 0.001). Inflammatory response could not be
      detected in either group three days after injection of IRBP 1-20-specific T
      cells. Both groups of mice had the most severe inflammatory response on the 14 th
      day, of which that of the IL-23 group was significantly more severe. CONCLUSIONS:
      IL-23 facilitates IRBP 1-20-specific T cells to differentiate into Th17, whereas
      IL-2 inhibits this process and induces these cells to differentiate towards Th1.
      Further studies showed that the pathogenicity of Th17 cells was significantly
      higher than that of Th1 cells.

PMID- 23866704
TI  - [Randomly sampling survey of dry eye awareness in general eye clinic].
AB  - OBJECTIVE: To determine the dry eye awareness in the populations visiting general
      eye clinic. METHODS: This was a cross-sectional study. A questionnaire about dry
      eye was designed and administrated to Peking University Third Hospital General
      Eye Clinic patients (n = 804) from June 2010 to June 2011. The questionnaire
      contents included general demographic characteristics, experience of health
      related work, past medical history, medication history and ocular surface
      symptoms associated with dry eye, contact lens wearing, ocular operation history,
      etc. Chi-square and Binary logistic regression analysis was used to determine the
      influence of demographic and clinical features on awareness of dry eye. RESULTS:
      Awareness of "dry eye" in the general eye clinical patients was relatively low
      (26.9%, 216/804). Participants whose age were between 40 and 60 years had better
      dry eye awareness (41.7%, 73/175) (chi(2) = 27.365, P = 0.000). Dry eye awareness
      of female was better than that of male [female: 33.8% (151/447), male: 18.2%
      (65/357), chi(2) = 24.500, P = 0.000]. Those who had been in health-related work
      (71.4%, 30/42), and whose friends or relatives were ophthalmologists (54.7%,
      52/95) had better dry eye awareness (chi(2) = 31.582, 36.400; both P < 0.01).
      Participants with a history of rheumatoid arthritis (7/10) or diabetes mellitus
      (63.0%, 17/27) had better dry eye awareness (chi(2) = 32.301, 29.887;both P <
      0.01). Those who had been using artificial tears (77.5%, 31/40), oral
      contraceptives (9/14), diuretics (10/18), sedatives (70.4%, 19/27) and anti
      depression drugs (4/4) had better dry eye awareness (chi(2) = 54.928, 10.154,
      7.713, 26.912, 10.943; all P < 0.01). Except frequently blinking (29.5%),
      participants who had ocular irrigating symptoms (all > 33.0%) had better
      awareness than those who had not (chi(2) = 7.831 - 32.522, all P < 0.01). Those
      who were allergic to environment irritating factors (all > 30.0%) had better
      awareness (chi(2) = 5.033 - 24.564, all P < 0.01). Participants who had medical
      history of ocular surgery (47.2%, 34/72), experience of wearing contact lens
      (33.2%, 94/283), who were diagnosed as dry eye (100.0%, 45/45) and who had
      regular ocular examinations (31.0%, 96/310) had better awareness (chi(2) = 4.321 
      129.763, all P < 0.01). Those who had visited general practitioners (14.8%,
      16/108) had lower awareness than those who went to hospital of higher level
      (28.7%, 200/696) (chi(2) = 9.324, P = 0.002). The result of binary logistic
      regression analysis showed that gender, health-related working experience,
      relatives or friends working as Ophthalmologists, using artificial tears, oral
      contraceptives and sedatives, ocular irritations or environment sensitivity, eye
      surgeries and wearing contact lens were factors that affected dry eye awareness
      (OR > 1.000, P < 0.10). CONCLUSIONS: Dry eye awareness in the population who
      visit general eye clinic is low. The knowledge of dry eye should be added to the
      patient education and public popularization.

PMID- 23866705
TI  - [Selection of the posterior chamber phakic intraocular lens length].
AB  - OBJECTIVE: To evaluate the efficacy, safety and clinical value of calculating the
      posterior chamber phakic intraocular lens (ICL) length according to the corneal
      horizontal diameter. METHODS: This was a retrospective study. A Staar Visian
      implantable contact lens (ICL) was implanted in 32 patients (64 eyes) with high
      myopia in the Department of Ophthalmology, the First Affiliated Hospital, College
      of Medicine, Zhejiang University between November 15, 2005 and January 15, 2011.
      The lens length was calculated according to the corneal horizontal diameter
      measured by Orbscan II. Patients were followed up postoperatively at 1 day, 1
      week, 1, 3, 6 and 12 months and every 6 months thereafter. The evaluations
      included visual acuity, manifest refraction, applanation tonometry, endothelial
      cell count, slit-lamp microscopy to detect cataract, and UBM to assess the degree
      of ICL tilt and distances between the corneal endothelium, the ICL, and the
      crystalline lens. All of the preoperative and 12-month follow-up observations
      were analyzed using SPSS 16.0 software. RESULTS: No anterior subcapsular
      cataracts were found in any of the eyes after surgery. Pigmentary dispersion was
      observed on the anterior and posterior surface of the ICL, but the difference was
      not statistically significant (chi(2) = 2.24, P = 0.13). The intraocular pressure
      changed from (15.67 +/- 3.23) mm Hg (1 mm Hg = 0.133 kPa) to (15.78 +/- 3.23) mm
      Hg, but the difference was not significant (t = 0.24, P = 0.38). The corneal
      endothelium-lens (central section) distance measured by UBM postoperatively was
      (2.97 +/- 0.25) mm and the corneal endothelium-ICL (central section) distance was
      (2.24 +/- 0.27) mm; the difference between them was statistically significant (t
      = 15.77, P < 0.01). The degree of ICL tilt measured by UBM was 1.20 degrees  +/-
      1.05  degrees . The percentage of eyes with a trabecular-iris angle (TIA) greater
      than 30 degrees , between 21 degrees  and 30 degrees , between 11 degrees and 20
      degrees , and smaller than 10 degrees  were 29.1%, 50.0%, 11.6%, and 9.3%,
      respectively. The angle opening distance at 500 micron (AOD500) measured by UBM
      postoperatively was (0.32 +/- 0.15) mm. The contact distance between the iris and
      the ICL measured by UBM postoperatively was (0.85 +/- 0.46) mm and the ICL-lens
      central distance was (0.47 +/- 0.25) mm. The Pearson's correlation coefficients
      between the ICL-lens central distance and the corneal horizontal diameter, sulcus
      diameter, anterior chamber depth(ACD) and ICL length were 0.11, 0.16, 0.04 and
      0.19, respectively; none were statistically significant. The ICL-lens peripheral
      distance measured by UBM postoperatively was (0.25 +/- 0.20) mm. CONCLUSION:
      Selecting the length of the ICL according to the corneal horizontal diameter is
      appropriate, and assures the safety, effectiveness and predictability of ICL
      implantation.

PMID- 23866706
TI  - [Modified orbital decompression for severe thyroid associated ophthalmopathy].
AB  - OBJECTIVE: To present a new technique for orbital decompression that minimizes
      surgical approaches while maximizing the removed areas of orbital walls and to
      evaluate the efficacy and safety of it for patients with severe thyroid
      associated ophthalmopathy (TAO). METHODS: A retrospective review of 40 cases (66
      eyes) with severe TAO undergoing the modified decompression between January 2009
      and January 2011 was conducted. All patients were assigned to three groups, which
      were group CON: compressive optic neuropathy in 30 eyes, group MP: marked
      proptosis in 30 eyes, and group EK: exposure keratopathy in 6 eyes. The deep
      lateral, medial walls and orbital floor decompressions were underwent via an
      eyelid crease or a lateral sub-brow S-shape approach with a transcaruncular
      approach. Clinical outcomes were recorded including visual acuity,
      exophthalmometry, diplopia, clinical activity score (CAS) and CT scans before and
      6 months after surgery. Intra- and postoperative complications were recorded.
      RESULTS: The postoperative visual acuity was improved in 17 eyes (56.7%, P <
      0.05) of group CON. The mean proptosis reduction was (8.1 +/- 2.7) mm (t = 11.73,
      P < 0.01) and (11.4 +/- 3.1) mm (t = 15.52, P < 0.01) in group CON and group MP,
      respectively. The CAS was decreased in group CON (P < 0.01). Compared with
      preoperative records, the degree of diplopia was not significantly different in
      group CON (U = 131.0, P = 0.309) and group MP (U = 157.5, P = 0.881). Diplopia
      resolved in 7 cases (39%) of group CON, 5 cases (28%) of group MP. New-onset
      diplopia or its aggravation was recorded in 3 cases (17%) of group CON, 4 cases
      (22%) of group MP. The other postoperative improvement included recovered color
      vision, reduced intraocular pressure, and healing keratopathy. The important
      complications were intraoperative dural tears, new-onset diplopia and ocular
      inferior displacement. CONCLUSIONS: The modified orbital decompression offers
      wide exposure to the three orbital walls, marked proptosis reduction, and no
      apparent scar. It is efficacious and safety for the treatment of CON and
      inflammatory activity of TAO without serious complications, meanwhile, has little
      risk of induced diplopia.

PMID- 23866707
TI  - [Repeatability and agreement of corneal thickness measurement with Pentacam
      Scheimpflug photography and Visante optical coherence tomography].
AB  - OBJECTIVE: To evaluate the repeatability and agreement of central and peripheral
      corneal thickness (CT) measurements by high resolution Pentacam rotating
      Scheimpflug photography and Visante optical coherence tomography (OCT) in
      unoperated myopic eyes and eyes after Laser In Situ Keratomileusis (LASIK).
      METHODS: CT at central, thinnest, 1.0 mm and 2.5 mm superior, inferior, nasal and
      temporal periphery locations, and the location of the corneal thinnest thickness
      were measured using Pentacam and Visante OCT in 60 myopia patients (60 eyes) and
      60 patients (60 eyes) after LASIK. The results were analyzed by paired-t test,
      Pearson correlation analysis and Bland-Altman method. RESULTS: Both Pentacam and
      Visante OCT demonstrated high intraobserver repeatability, with all intraclass
      correlation coefficients and Cronbach's alphas were more than 0.9, and
      coefficient of variation were less than 0.9%. Significantly higher CoV was
      measured with Pentacam than by Visante OCT in at central (0.46 +/- 0.30),
      thinnest (0.43 +/- 0.28) and 1.0 mm locations in both groups (t = 2.465, 2.226, P
      < 0.05), but no statistically significant difference were found at 2.5 mm
      locations in healthy subjects and all locations in post-LASIK eyes (t = -0.518,
      1.542, -0.876, 0.756, P > 0.05). The thickness of central corneal with Pentacam
      was (543.01 +/- 22.89) um, the thinnest point was (540.61 +/- 22.84) um, they
      were greater than the value of Visante OCT (t = 17.946, 23.071, P < 0.05). The
      Pearson correlation coefficients were all more than 0.9 (all r > 0.9, P < 0.01).
      The Bland-Altman plots showed the 95% LoA between both devices were lower than 22
      um at central, thinnest and 1.0 mm locations. However, the 95% LoA were 24 um to
      44 um at 2.5 mm locations. CONCLUSIONS: Pentacam and Visante OCT demonstrate high
      repeatability for central and peripheral CT measurements in young myopia and post
      LASIK eyes. However, both devices can't be used interchangeably for measurements
      of peripheral CT.

PMID- 23866708
TI  - [Comparison of I Care rebound tonometer and Goldmann applanation tonometer after
      Descemet's stripping with automated endothelium keratoplasty].
AB  - OBJECTIVE: To evaluate the influence of corneal thickness (CT) on the intraocular
      pressure (IOP) measurements, the agreement of IOP readings with I Care rebound
      tonometer (RBT) and Goldmann applanation tonometer (GAT), and the agreement of
      central and peripheral IOP values obtained by RBT. METHODS: Thirty-seven eyes of
      34 patients after Descemet's stripping with automated endothelium keratoplasty
      (DSAEK) underwent CT measurement using anterior segment OCT (AS-OCT) followed by
      IOP evaluation with the GAT at corneal center and with the RBT at corneal center
      and at 1 mm from the limbus in the nasal and temporal directions. The mean IOP
      measurement by the RBT and measurement by the GAT were analysed by paired t test.
      Pearson correlation analysis were performed to assess the correlations between
      the measurement and the influence of CT on IOP values. Agreement between the
      tonometers was calculated using the Bland-Altman method. RESULTS: IOP obtained by
      GAT was (16.2 +/- 4.7) mm Hg (1 mm Hg = 0.133 kPa), and IOP obtained from central
      cornea, nasal cornea and temporal cornea by RBT were (16.0 +/- 5.3) mm Hg, (17.4
      +/- 5.0) mm Hg and (17.1 +/- 5.0) mm Hg, respectively. There was no statistical
      difference between the IOP on central cornea obtained by GAT and RBT (t = 0.77, P
      = 0.446), IOP on the peripheral cornea were higher than on central cornea by RBT
      (t = 3.24, 3.17, P = 0.003), and they were positively correlated (r = 0.869,
      0.911, P < 0.05). The IOP readings showed positive relationship to CT values.
      Bland-Altman scatter plots showed reasonable inter-method agreement between each
      technique of IOP measurements. CONCLUSIONS: After DSAEK, the IOP readings
      obtained by RBT or GAT show positive relationship to CT values. There are
      reasonable agreements between each technique of IOP measurements. Considering the
      special advantages, RBT is an effective method to observe the IOP changes after
      DSAEK.

PMID- 23866709
TI  - [Congenital dacryocystocele: presentation and treatment].
AB  - OBJECTIVE: To report the presentation, complications, and treatment strategies
      for infants with congenital dacryocystocele. METHOD: We performed a retrospective
      chart review of all patients presenting with dacryocystoceles to Beijing
      Children's Hospital between 2007 and 2011. RESULTS: Thirty-one patients (33 eyes)
      were identified, presenting at a median age of 10 days of life. Twenty-four
      (72.72%) patients presented with cellulitis or dacryocystitis and required
      systemic antibiotics. Two (6.45%) patients presented with respiratory compromise.
      Resolution occurred with conservative treatment for 6 eyes, but 27 (81.82%)
      required surgical intervention. All 27 eyes received probing, and 20 (74.07%)
      were successful. The other 7 eyes required marsupialization of an intranasal
      cyst. CONCLUSIONS: Although congenital dacryocystoceles may resolve with
      conservative measures, many become infected and require systemic antibiotic
      treatment, and most require surgical intervention. Referral in the early neonatal
      period can aid in timely intervention before complications such as infection
      occur.

PMID- 23866710
TI  - [The status and prospects of immunological research in uveitis].
AB  - Uveitis is a group of common sight-threatening intraocular inflammatory diseases.
      Besides of few patients caused by infectious agents, most of patients caused by
      the autoimmune reactions. In recent years, the basic and clinical researches in
      the immunology of uveitis had many advances. The complex immunologic mechanisms
      in uveitis were explained from the levels of cellular and molecular immunology.
      And the theoretical basis on the treatment of uveitis was established. But there
      are some unresolved questions existed in the fields of uveitis researches, such
      as the mechanisms of body defense system to prevent the intraocular inflammation,
      the pathogenesis of infection that causes the autoimmune response and the
      autoimmune uveoretinitis, the susceptible gene of uveitis and the related factors
      associated with occurrence and chronic in uveitis. The deeper studies on these
      questions will be benefit to the diagnosis and treatment of human refractory
      uveitis. 

PMID- 23866711
TI  - [Recent advances in gene therapy of uveitis].
AB  - Uveitis is a group of common eye disease and is one of the major causes of
      blindness worldwide. Corticosteroids and immunosuppressive agents are commonly
      used for the treatment of uveitis. However, long-term application of these drugs
      frequently lead to numerous side effects. Recently, with the development of gene
      transfer techniques, viral vector mediated gene therapy has achieved remarkable
      success in experimental uveitis. Inhibition of ocular inflammation in animal
      models is obtained mainly by two ways: first, increase of the expression of
      different immune modulators including IL-10, IL-1Ra, IL-4 and IFN-alpha, or IL
      27p28; secondly, induction of immune tolerance by transferring uveitis related
      antigens via viral vectors. Uveitis is characterized by long-lasting and
      recurrent, the unique properties of local administration, long-term effectiveness
      and minor side effects of gene therapy may provide a novel strategy for the
      treatment of the devastating uveitis. 

PMID- 23866712
TI  - [Research update of anti-TNF-alpha biologic agents in the treatment of uveitis].
AB  - Uveitis is one of the common sight-threatening eye diseases, which is usually
      recurrent and refractory to treatment. It is generally considered that the
      development of uveitis is closely related to the autoimmune response of uvea.
      Tumor necrosis factor (TNF)-alpha is one of the key cytokines involved in the
      emergence and progression of uveitis. Blocking the production or inhibiting the
      activity of TNF-alpha can inhibit the development or progression of uveitis.
      Presently, the commercially available TNF-alpha blockers include infliximab,
      adalimumab, etanercept, and golimumab. This review describes the clinical studies
      and adverse effects of TNF-alpha blockers in the treatment of uveitis, and
      discusses the principle for clinical use of TNF-alpha blockers in synergy with
      other immunosuppressive agents.

PMID- 23866713
TI  - Septal hematoma: always think about it!

PMID- 23866714
TI  - Group B streptococcal colonization in 160 mother-baby pairs: a prospective cohort
      study.
AB  - OBJECTIVES: To identify the source of postnatal colonization with group B
      Streptococcus (GBS) and to evaluate the impact of intrapartum antibiotic
      prophylaxis (IAP) administration in newborn infant transmission. STUDY DESIGN: A
      prospective, longitudinal study evaluated GBS colonization in 160 mother-baby
      pairs. Specimens were collected from the time of delivery to 8 weeks post-partum,
      from rectum, vagina, and milk of mothers, and from throat and rectum of neonates.
      Women were grouped according to their GBS status at discharge from the hospital:
      culture-positive carriers (n = 83), culture-negative carriers (n = 26), and
      noncarriers (n = 51). Newborns were considered colonized if GBS was yielded from
      at least 1 site. RESULTS: A total of 35 (21.9%) neonates were colonized; 30 were
      born to culture-positive carriers, 2 to culture-negative carriers, and 3 to
      noncarriers. Infants of culture-positive carriers exposed to IAP were less likely
      to be colonized (15/57 vs 15/26, P = .01), or heavily colonized, (7/57 vs 9/26, P
      = .04). Of all newborns, those exposed to IAP and discharged GBS-free from
      hospital, often became colonized subsequently (12/57 vs 1/26, P = .09). Molecular
      typing analysis (available for 30 of 32 carrier mothers and their infants)
      confirmed an identical strain of GBS in all mother-baby pairs. Six of 83 culture
      positive carrier mothers had a positive milk culture. Their respective neonates
      all were heavily colonized. CONCLUSIONS: Newborns exposed to IAP and GBS-free at
      hospital discharge subsequently acquire GBS from their mothers. Culture-positive
      milk is associated with heavy neonatal colonization.

PMID- 23866715
TI  - Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy.
AB  - OBJECTIVE: To estimate the age when cardiomyopathy develops in boys with Duchenne
      muscular dystrophy (DMD) and to analyze the effect of corticosteroid treatment on
      the age of cardiomyopathy onset. STUDY DESIGN: We identified a population-based
      sample of 462 boys with DMD, born between 1982 and 2005, in 5 surveillance sites
      in the US. Echocardiographic and corticosteroid treatment data were collected.
      Cardiomyopathy was defined by a reduced fractional shortening (<28%) or ejection
      fraction (<55%). The age of cardiomyopathy onset was determined. Survival
      analysis was performed to determine the effects of corticosteroid treatment on
      cardiomyopathy onset. RESULTS: The mean (SD) age of cardiomyopathy onset was 14.3
      (4.2) years for the entire population and 15.2 (3.4) years in corticosteroid
      treated vs 13.1 (4.8) in non-treated boys. Survival analysis described a
      significant delay of cardiomyopathy onset for boys treated with corticosteroids
      (P < .02). By 14.3 years of age, 63% of non-treated boys had developed
      cardiomyopathy vs only 36% of those treated. Among boys treated with
      corticosteroids, there is a significant positive effect of duration of
      corticosteroid treatment on cardiomyopathy onset (P < .0001). For every year of
      corticosteroid treatment, the probability of developing cardiomyopathy decreased
      by 4%. CONCLUSIONS: Oral corticosteroid treatment was associated with delayed
      cardiomyopathy onset. The duration of corticosteroid treatment also correlated
      positively with delayed cardiomyopathy onset. Our analysis suggests that a boy
      with DMD treated for 5 years with corticosteroids might experience a 20% decrease
      in the likelihood of developing cardiomyopathy compared with untreated boys.

PMID- 23866716
TI  - The oxygen paradox in the newborn: keep oxygen at normal levels.

PMID- 23866717
TI  - Timing of interventions in the delivery room: does reality compare with neonatal
      resuscitation guidelines?
AB  - OBJECTIVE: To determine the proportion of infants who had the tasks recommended
      in the neonatal resuscitation guidelines performed within 30 and 60 seconds of
      birth, and the time taken to perform each task. STUDY DESIGN: From video
      recordings in delivery rooms, we determined the time from birth and arrival on a
      resuscitation table to warm, assess heart rate (HR), attach an oximeter, and
      provide respiratory support for each infant. We determined the proportion of
      infants who had these tasks completed by 30 and 60 seconds, and the median time
      taken to perform each task. RESULTS: We reviewed and analyzed data from 189
      infants (median gestational age, 29 weeks [IQR, 27-34 weeks]; median birth
      weight, 1220 g [IQR, 930-2197 g]). Twelve infants (6%) were not on the
      resuscitation table within 30 seconds of birth. Less than 10% of infants were
      placed in polyethylene bags or had their HR determined by 30 seconds. By 60
      seconds, 48% were in polyethylene bags, 33% had their HR determined, 38% received
      respiratory support, and 60% had an oximeter attached. The median time taken to
      perform all tasks was greater than that recommended in the guidelines.
      CONCLUSION: Most newborns were not managed within the time frame recommended in
      resuscitation guidelines. The recommended 30- and 60-second intervals may be too
      short.

PMID- 23866718
TI  - Successful rehabilitation in pediatric ultrashort small bowel syndrome.
AB  - OBJECTIVE: To examine treatment outcomes in pediatric patients with ultrashort
      small bowel (USSB) syndrome in an intestinal rehabilitation program (IRP). STUDY
      DESIGN: We reviewed IRP records for 2001-2011 and identified 28 children with
      USSB (<= 20 cm of small bowel). We performed univariate analysis using the Fisher
      exact test and Wilcoxon rank-sum test to compare characteristics of children who
      achieved parenteral nutrition (PN) independence with intact native bowel and
      those who did not. Growth, nutritional status, and hepatic laboratory test
      results were compared from the time of enrollment to the most recent values using
      the Wilcoxon signed-rank test. RESULTS: Of the 28 patients identified, 27 (96%)
      survived. Almost one-half (48%) of these survivors achieved PN independence with
      their native bowel. The successfully rehabilitated patients were more likely to
      have an intact colon and ileocecal valve (P = .01). Significant improvements in
      PN kcal/kg, total bilirubin, and height and weight z-scores were seen in all
      patients, but serum hepatic transaminase levels did not improve in the
      nonrehabilitated patients. CONCLUSION: Enrollment in an IRP provides an excellent
      probability of survival for children with USSB. The presence of an intact
      ileocecal valve and colon are positively associated with rehabilitation in this
      population, but are not requisite. Approximately one-half of patients with USSB
      can achieve rehabilitation, with a median time to PN independence of less than 2
      years. The USSB population can attain reduced PN dependence, improvement of PN
      associated liver disease, and enhanced growth with the aid of an IRP.

PMID- 23866719
TI  - Trends in sugar supply and consumption in Australia: is there an Australian
      Paradox?
AB  - BACKGROUND: High consumption of refined carbohydrate, in particular sugar, has
      been identified as a possible contributory factor in greater risk of excess
      weight gain. In spite of data limitations, one recent paper suggests that
      Australian sugar consumption has decreased over the same time period that obesity
      has increased, a so called 'Australian Paradox'. Given the significant public
      health focus on nutrition, we aimed to estimate Australian sugar supply and
      consumption over recent decades, to determine whether these data could be used to
      make any conclusions about sugar's role in obesity. METHODS: Foods high in sugar
      were identified. Data relating to sugar supply and consumption from 1988 to 2010
      were obtained from multiple sources. Using these data we attempted to generate a
      time series estimate of sugar in Australia's food supply. RESULTS: Australia
      produces and exports sugar from sugar cane and the sugar in imported foods has
      received little attention. We were unable to produce a reliable and robust
      estimate of total sugars in the Australian diet due to data limitations and a
      lack of current data sources. However, available Import data showed large
      increases in the volume and value of imported sweetened products between 1988 and
      2010 to over 30 grams of sugar per person per day. Value estimates of local
      production of sweetened products also show substantial increases in this period.
      CONCLUSION: The Australian Paradox assertion is based on incomplete data, as it
      excludes sugar contained in imported processed foods, which have increased
      markedly. A major Australian public health target is to improve the quality of
      the food supply, and actions have been set in terms of achieving broader
      environmental changes. However, evaluation of progress is hampered by lack of
      high quality data relating to supply and consumption. We recommend the regular
      collection of comprehensive food supply statistics, which include both local
      production and imports. This would provide an inexpensive addition to survey data
      and could assist in monitoring sugar consumption trends in food supply. Such
      information would also help inform public health policy.

PMID- 23866720
TI  - Immune status and function in harbor seal pups during the course of
      rehabilitation.
AB  - Routine hematological and serum chemistry parameters are important tools for the
      evaluation of health and the treatment of marine mammals admitted to
      rehabilitation centers. The evaluation of phagocytosis, oxidative burst and
      immunoglobulin G (IgG), as markers of immune system function, and haptoglobin
      (Hp), as a stress marker, were evaluated alongside routine hematology and
      chemistry as potentially informative diagnostic tools for marine mammal health
      assessments. Blood samples from harbor seal pups (Phoca vitulina) admitted to
      (n=46), and released from (n=28), the Vancouver Aquarium's Marine Mammal Rescue
      Center (VAMMRC) were collected (1) to perform routine and novel functional
      approaches to evaluate the health of pups at admission; (2) to determine how
      these parameters changed during the rehabilitation process; and (3) to generate
      baseline values for reference purposes. Sodium was the only blood parameter which
      differed between seal pups that survived and those that died, with the surviving
      pups exhibiting higher levels on admission diagnostics. Positive correlations
      between total protein concentrations, IgG and Hp levels were observed with
      globulin concentrations of seal pups. Changes in serum chemistry values between
      admission and release included a decrease in red blood cells (RBCs), glucose,
      bicarbonate, total bilirubin, gamma-glutamyltransferase (GGT) levels, and an
      increase in mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell
      hemoglobin concentration (MCHC), lymphocytes, eosinophils, urea, potassium, anion
      gap, calcium, phosphorus, total protein, albumin, globulin and osmolality levels.
      During the rehabilitation process, phagocytosis decreased, while Hp levels
      increased. Age and improved health appeared to underlie changes in these
      parameters during the rehabilitation period. 

PMID- 23866721
TI  - Surface modification of PLGA nanoparticles via human serum albumin conjugation
      for controlled delivery of docetaxel.
AB  - BACKGROUND: Poly lactic-co-glycolic acid (PLGA) based nanoparticles are
      considered to be a promising drug carrier in tumor targeting but suffer from the
      high level of opsonization by reticuloendothelial system due to their hydrophobic
      structure. As a result surface modification of these nanoparticles has been
      widely studied as an essential step in their development. Among various surface
      modifications, human serum albumin (HSA) possesses advantages including small
      size, hydrophilic surface and accumulation in leaky vasculature of tumors through
      passive targeting and a probable active transport into tumor tissues. METHODS:
      PLGA nanoparticles of docetaxel were prepared by emulsification evaporation
      method and were surface conjugated with human serum albumin. Fourier transform
      infrared spectrum was used to confirm the conjugation reaction where nuclear
      magnetic resonance was utilized for conjugation ratio determination. In addition,
      transmission electron microscopy showed two different contrast media in
      conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel,
      unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells.
      RESULTS: Size, zeta potential and drug loading of PLGA nanoparticles were about
      199 nm, -11.07 mV, and 4%, respectively where size, zeta potential and drug
      loading of conjugated nanoparticles were found to be 204 nm, -5.6 mV and 3.6%
      respectively. Conjugated nanoparticles represented a three-phasic release pattern
      with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment
      showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 MUg) was
      significantly lower than both free docetaxel (20.2 MUg) and unconjugated PLGA
      nanoparticles (6.2 MUg). CONCLUSION: In conclusion surface modification of PLGA
      nanoparticles through HSA conjugation results in more cytotoxicity against tumor
      cell lines compared with free docetaxel and unconjugated PLGA nanoparticles.
      Albumin conjugated PLGA nanoparticles may represent a promising drug delivery
      system in cancer therapy.

PMID- 23866722
TI  - The methylenetetrahydrofolate reductase polymorphism (MTHFR c.677C>T) and
      elevated plasma homocysteine levels in a U.S. pediatric population with incident
      thromboembolism.
AB  - OBJECTIVE: Elevated plasma homocysteine (tHcy) and the MTHFR c.677C>T variant
      have been postulated to increase the risk of venous thromboembolism (VTE),
      although mechanisms and implications to pediatrics remain incompletely
      understood. The objectives of this study were to determine the prevalences of
      elevated tHcy and MTHFR variant in a pediatric population with VTE or arterial
      ischemic stroke (AIS), and to determine associations with thrombus outcomes.
      STUDY DESIGN: Subjects were enrolled in an institution-based prospective cohort
      of children with VTE or AIS. Inclusion criteria consisted of objectively
      confirmed thrombus, <=21years at diagnosis, tHcy measured and MTHFR c.677C>T
      mutation analysis. Clinical and laboratory data were collected. Frequencies for
      elevated tHcy and MTHFR variant were compared with NHANES values for healthy US
      children and also between study groups (VTE vs AIS, provoked vs idiopathic) and
      by age. RESULTS: The prevalences of hyperhomocysteinemia or MTHFR variant were
      not increased in comparison to NHANES. tHcy did not differ between those with
      wild-type MTHFR versus either c.677C>T heterozygotes or homozygotes. There was no
      association between tHcy or MTHFR variant and thrombus outcomes. CONCLUSION: In
      this cohort of US children with VTE or AIS, neither the prevalence of
      hyperhomocysteinemia nor that of MTHFR variant was increased relative to
      reference values, and adverse thrombus outcomes were not definitively associated
      with either. While it is important to consider that milder forms of pyridoxine
      responsive classical homocystinuria will be detected only by tHcy, we suggest
      that routine testing of MTHFR c.677C>T genotype as part of a thrombophilia
      evaluation in children with incident thromboembolism is not warranted until
      larger studies have been performed in order to establish or refute a link between
      MTHFR and adverse outcomes.

PMID- 23866723
TI  - Public beliefs about the causes of obesity and attitudes towards policy
      initiatives in Great Britain.
AB  - OBJECTIVE: To assess attributions for overweight and the level of support for
      policy initiatives in Great Britain. DESIGN: Cross-sectional. Respondents
      indicated their agreement (5-point scales: strongly disagree to strongly agree)
      to three potential causes of overweight (environment, genes, willpower) and five
      policies (free weight-loss treatment, taxing unhealthy foods, healthy lifestyle
      campaigns, food labelling, advertising restrictions). SETTING: Data were
      collected as part of a computer-assisted, face-to-face Omnibus survey of adults
      (aged >15 years) from across Great Britain in April 2012 carried out by a market
      research company. SUBJECTS: A population-representative sample of British adults
      (n 1986). RESULTS: More people attributed overweight to the food environment (61
      %) and lack of willpower (57 %) than to genes (45 %). Policy support was highest
      for healthy lifestyle campaigns (71 %) and food labelling (66 %), and lowest for
      taxing unhealthy foods (32 %). Food environment attributions were associated with
      higher support for all policies (P < 0.001). Genetic attributions were associated
      with higher support for free weight-loss treatments and healthy lifestyle
      campaigns (P < 0.001), but not other policies. Attributions to lack of willpower
      were not associated differentially with support for any policies (P > 0.01).
      CONCLUSIONS: Belief that overweight is caused by the food environment or genes -
      both seen as outside individual control - was associated with greater support for
      government policies to prevent and treat obesity. Improving awareness of the
      multiple causes of obesity could facilitate acceptance of policy action to reduce
      obesity prevalence.

PMID- 23866724
TI  - Intracerebroventricular administration of lipopolysaccharide induces indoleamine
      2,3-dioxygenase-dependent depression-like behaviors.
AB  - BACKGROUND: Activation of the tryptophan degrading enzyme indoleamine-2,3
      dioxygenase 1 (IDO1) is associated with the development of behavioral signs of
      depression. Systemic immune challenge induces IDO1 in both the periphery and the
      brain, leading to increased circulating and brain concentrations of kynurenines.
      However, whether IDO1 activity within the brain is necessary for the
      manifestation of depression-like behavior of mice following a central immune
      challenge remains to be elucidated. METHODS: We investigated the role of brain
      IDO1 in mediating depression-like behavior of mice in response to
      intracerebroventricular injection of saline or lipopolysaccharide (LPS, 10 ng).
      RESULTS: LPS increased the duration of immobility in the tail suspension test and
      decreased preference for a sucrose solution. These effects were associated with
      an activation of central but not peripheral IDO1, as LPS increased brain
      kynurenine but had no effect on plasma concentrations of kynurenine.
      Interestingly, genetic deletion or pharmacological inhibition of IDO1, using 1
      methyl-tryptophan, abrogated the reduction in sucrose preference induced by
      intracerebroventricular LPS. 1-Methyl-tryptophan also blocked the LPS-induced
      increase in duration of immobility during the tail suspension test. CONCLUSIONS:
      These data indicate that activation of brain IDO1 is sufficient to induce
      depression-like behaviors of mice in response to central LPS.

PMID- 23866725
TI  - Hydrotherapy as a recovery strategy after exercise: a pragmatic controlled trial.
AB  - BACKGROUND: Our aim was to evaluate the recovery effects of hydrotherapy after
      aerobic exercise in cardiovascular, performance and perceived fatigue. METHODS: A
      pragmatic controlled repeated measures; single-blind trial was conducted. Thirty
      four recreational sportspeople visited a Sport-Centre and were assigned to a
      Hydrotherapy group (experimental) or rest in a bed (control) after completing a
      spinning session. Main outcomes measures including blood pressure, heart rate,
      handgrip strength, vertical jump, self-perceived fatigue, and body temperature
      were assessed at baseline, immediately post-exercise and post-recovery. The
      hypothesis of interest was the session*time interaction. RESULTS: The analysis
      revealed significant session*time interactions for diastolic blood pressure
      (P=0.031), heart rate (P=0.041), self perceived fatigue (P=0.046), and body
      temperature (P=0.001); but not for vertical jump (P=0.437), handgrip (P=0.845) or
      systolic blood pressure (P=0.266). Post-hoc analysis revealed that hydrotherapy
      resulted in recovered heart rate and diastolic blood pressure similar to baseline
      values after the spinning session. Further, hydrotherapy resulted in decreased
      self-perceived fatigue after the spinning session. CONCLUSIONS: Our results
      support that hydrotherapy is an adequate strategy to facilitate cardiovascular
      recovers and perceived fatigue, but not strength, after spinning exercise. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01765387.

PMID- 23866727
TI  - A case-based discussion on a patient with non-otogenic fungal skull base
      osteomyelitis: pitfalls in diagnosis.
AB  - OBJECTIVE: To discuss the diagnostic pitfalls and limitations of imaging
      investigations in non-otogenic skull base osteomyelitis. CASE REPORT: This paper
      reports a fatal case of non-otogenic fungal skull base osteomyelitis in an
      immunosuppressed patient. The patient initially presented with headache and later
      diplopia during multiple hospital admissions. A retrospective review of the
      initial imaging studies of his skull base revealed subtle signs of early
      infection at the inferior portion of the nasopharynx. Biopsies were taken from
      the posterior nasopharyngeal wall. Fungal cultures isolated Aspergillus fumigatus
      and mucor species. CONCLUSION: The insidious onset of the clinical features and
      the limitations of the currently available investigations make early diagnosis of
      skull base osteomyelitis difficult. This case highlights that skull base
      osteomyelitis should be suspected in immunocompromised patients with subtle
      radiological abnormalities on initial imaging. There is still controversy
      regarding the

PMID- 23866728
TI  - Pediatric femoral shaft fractures: treatment strategies according to age--13
      years of experience in one medical center.
AB  - OBJECTIVE: The objective of this study was to analyze our experience in treating
      femoral shaft fractures with different strategies, focusing on the first year
      after injury when the choice of method would have the greatest impact. METHODS:
      We reviewed the medical records of all children treated for femoral shaft
      fractures in our institution between 1997 and 2010. They were divided according
      to therapeutic approach: spica cast, skin traction, titanium elastic nail (TEN),
      external fixator, intramedullary medullary nail (IMN), and plating. RESULTS: The
      212 patients included 150 boys and 62 girls (M/F ratio 2.4:1, mean age 5 years,
      range 0-16). The postoperative radiographic results demonstrated solid union in
      all patients, with no malunions. Of the 151 children in the spica cast group, 10
      required re-manipulation and casting due to loss of reduction with unaccepted
      angulation, 10 had contact dermatitis, and 2 had fever and pressure sores. All 21
      elastic nail group children underwent re-operation to remove the hardware: 3 had
      soft tissue irritation at the insertion points, and 3 had leg length discrepancy
      (LLD). Of the 14 external fixation patients, 4 had LLD, 1 had a pin tract
      infection, and 1 had a fracture through a pinhole after a fall. There were no
      complications in the 12 IMN patients, the 3 plating patients, or the 11 skin
      traction patients. LLD rates in the spica group were 10.5% higher compared to
      those in the control group (other treatment modalities) (P = .03). CONCLUSIONS:
      TEN treatment was superior to spica casting for children who had reached an
      average age of 4 years.

PMID- 23866729
TI  - Effects of chlorothalonil on development and growth of amphibian embryos and
      larvae.
AB  - Chlorothalonil is a broad spectrum fungicide widely used in agricultural and
      urban environments, yet little is known regarding its effects on amphibians. We
      examined effects of chlorothalonil on growth, malformations, and mortality in
      embryos and larvae of Xenopus laevis and Spea multiplicata, and assessed
      variation in sensitivity among aquatic organisms using a species sensitivity
      distribution (SSD). Chlorothalonil induced gut malformations in X. laevis embryos
      and inhibited growth. Tail degeneration was observed in larvae of both species
      and reduced tail length to total length ratios occurred at environmentally
      relevant concentrations (5.9 and 11.0 MUg/L). The mechanism of tail degeneration
      is unclear, but alteration in the expression of genes involved in tail resorption
      is a hypothesized mechanism. Larval amphibians were more sensitive than
      invertebrates and fish. Based on our results and the range of reported
      environmental concentrations, chlorothalonil may pose a risk to larval amphibians
      in certain habitats and scenarios.

PMID- 23866731
TI  - Relation of admission glucose levels, short- and long-term (20-year) mortality
      after acute myocardial infarction.
AB  - We examined temporal trends in mortality after myocardial infarction from 1985 to
      2008 depending on admission glucose levels. We included 11,324 consecutive
      patients admitted to our intensive coronary care unit for myocardial infarction
      from 1985 to 2008. Patients were categorized into normal, mild, and severe
      hyperglycemia groups (admission glucose levels <140, 140 to 200, and >=200 mg/dl,
      respectively). Temporal trends were determined using 3 groups: 1985 to 1990, 1990
      to 2000, and 2000 to 2008. The prevalence of hyperglycemia increased from 26% in
      the 1980s to 49% in the 2000s. The prevalence of hyperglycemia primarily
      increased in patients without diabetes. Kaplan-Meier mortality was 4%, 8%, and
      17% at 30 days and 64%, 71%, and 82% at 20 years in patients with normal, mild,
      and severe hyperglycemia, respectively. Compared with normal admission glucose
      level, adjusted 30-day mortality was 3.6-fold greater (95% confidence interval
      2.9 to 4.3) in patients with severe hyperglycemia. This association was not
      dependent on diabetic status (p for interaction = 0.43) but was dependent on the
      decade of hospitalization with a stronger association from 2000 to 2008 (adjusted
      odds ratio 7.7, 95% confidence interval 5.4 to 11, p for interaction <0.001).
      Compared with diabetes, hyperglycemia was a better discriminator for 30-day
      mortality. Mortality at 30 days decreased from 1985 to 2008, however, it
      decreased less in patients with hyperglycemia compared with those with
      normoglycemia. In conclusion, elevated admission glucose levels are common in
      patients with myocardial infarction and are strongly associated with increased
      mortality. Mortality decreased less from 1985 to 2008 in patients with
      hyperglycemia compared with those with normoglycemia. Efforts that establish
      optimal treatment for these patients remain warranted.

PMID- 23866730
TI  - Involving service users in trials: developing a standard operating procedure.
AB  - BACKGROUND: Many funding bodies require researchers to actively involve service
      users in research to improve relevance, accountability and quality. Current
      guidance to researchers mainly discusses general principles. Formal guidance
      about how to involve service users operationally in the conduct of trials is
      lacking. We aimed to develop a standard operating procedure (SOP) to support
      researchers to involve service users in trials and rigorous studies. METHODS:
      Researchers with experience of involving service users and service users who were
      contributing to trials collaborated with the West Wales Organisation for Rigorous
      Trials in Health, a registered clinical trials unit, to develop the SOP. Drafts
      were prepared in a Task and Finish Group, reviewed by all co-authors and
      amendments made. RESULTS: We articulated core principles, which defined equality
      of service users with all other research team members and collaborative processes
      underpinning the SOP, plus guidance on how to achieve these. We developed a
      framework for involving service users in research that defined minimum levels of
      collaboration plus additional consultation and decision-making opportunities. We
      recommended service users be involved throughout the life of a trial, including
      planning and development, data collection, analysis and dissemination, and listed
      tasks for collaboration. We listed people responsible for involving service users
      in studies and promoting an inclusive culture. We advocate actively involving
      service users as early as possible in the research process, with a minimum of two
      on all formal trial groups and committees. We propose that researchers protect at
      least 1% of their total research budget as a minimum resource to involve service
      users and allow enough time to facilitate active involvement. CONCLUSIONS: This
      SOP provides guidance to researchers to involve service users successfully in
      developing and conducting clinical trials and creating a culture of actively
      involving service users in research at all stages. The UK Clinical Research
      Collaboration should encourage clinical trials units actively to involve service
      users and research funders should provide sufficient funds and time for this in
      research grants.

PMID- 23866732
TI  - Therapeutic management changes and mortality rates over 30 years in ventricular
      septal rupture complicating acute myocardial infarction.
AB  - Recent studies have shown that the decrease in ventricular septal rupture (VSR)
      incidence after acute myocardial infarction is related to the improvement of
      reperfusion strategies. Our main objective was to explore the influence of
      therapeutic management changes on post-infarct VSR patient outcomes in a single
      reference center over a period of 30 years. We analyzed therapeutic management
      strategies and mortality rates in 228 patients with VSR after acute myocardial
      infarction admitted from 1981 to 2010. Patients were classified in 3 successive
      decades. There were no significant differences in clinical characteristics of
      patients with VSR at admission among those decades. Overall, surgery was
      performed in 159 patients (71.9%), primary transcatheter VSR closure was
      attempted in 5 patients (2.2%), and 64 patients (27.6%) were managed medically.
      Independent predictors of in-hospital mortality were VSR surgical repair (odds
      ratio [OR] 0.22, 95% confidence interval [CI] 0.1 to 0.7, p = 0.008), cardiogenic
      shock (OR 6.06, 95% CI 2.8 to 13.1, p <0.0001), and Killip class on admission (OR
      1.75, 95% CI 1.1 to 9.9, p = 0.02). We found a significant 1-year mortality
      reduction between the first and second decades (hazard ratio 0.48, 95% CI 0.28 to
      0.80; p = 0.005), with no significant change in the last decade (p = 0.2). This
      change was related to a systematic referral to surgical repair and shorter delays
      to VSR surgery (5.2 +/- 6.3 vs 1.9 +/- 3.2 days from first to second decade; p =
      0.012). In conclusion, surgical repair remains the only significant efficient
      therapy to reduce mortality in patients with VSR (p <10(-3)). In-hospital
      prognosis remains disappointing. This contrasts with the favorable long-term
      outcome of patients who survive the perioperative period and are discharged from
      hospital.

PMID- 23866733
TI  - Trends in acute kidney injury and outcomes after early percutaneous coronary
      intervention in patients >=75 years of age with acute myocardial infarction.
AB  - We analyzed the Nationwide Inpatient Sample database from 2002 to 2010 to examine
      the temporal trends in incidence of acute kidney injury (AKI), AKI requiring
      dialysis, and associated in-hospital mortality in patients >=75 years of age
      hospitalized with acute myocardial infarction and undergoing early (within 24
      hours) percutaneous coronary intervention. Of 2,225,707 patients >=75 years of
      age with acute myocardial infarction, 233,508 (10.5%) underwent early
      percutaneous coronary intervention, of which 21,961 (9.4%) developed AKI and
      1,257 (0.54%) developed AKI requiring dialysis. From 2002 to 2010, the incidence
      of AKI increased from 5.6% to 14.2% (p for trend <0.001) and that for AKI
      requiring dialysis decreased (0.6% to 0.4%; p for trend 0.018). Compared with
      2002, multivariable-adjusted odds ratios and 95% confidence intervals for AKI,
      AKI requiring dialysis, and in-hospital mortality in 2010 were 1.87 (1.71 to
      2.05), 0.20 (0.15 to 0.27) and 0.74 (0.60 to 0.90), respectively. In conclusion,
      among hospitalized adults >=75 years of age, from 2002 to 2010, there was an
      increase in AKI, but there was paradoxical decrease in AKI requiring dialysis and
      in-hospital mortality, potentially reflecting increased health-care provider
      awareness resulting in early recognition and implementation of renal-protective
      strategies and diagnosis-related group creep.

PMID- 23866734
TI  - Dobutamine-induced myocardial ischemia and ST-segment elevation in collateral
      dependent myocardium.
AB  - In patients with obstructive coronary artery disease, electrocardiographic (ECG)
      ST-segment elevation (STE) is frequently seen during dobutamine stress
      echocardiography (DSE) in leads overlying previous transmural left ventricular
      (LV) myocardial infarction. The mechanism of occasional STE during DSE in LV
      region with inducible myocardial ischemia and no previous myocardial infarction
      has not been well delineated. We retrospectively identified 28 adults (age 51 to
      83 years [69 +/- 8]; 82% men) with STE (>1 mm at >=80 ms after J point in >=2
      contiguous leads without pathologic Q waves) and inducible myocardial ischemia in
      the same territory during DSE. STE occurred in inferior (n = 16), inferolateral
      (n = 8), anterior (n = 1), lateral (n = 2), or anterolateral (n = 1) leads and
      was associated with ischemic symptoms in 17 patients (61%). Inducible LV wall
      motion abnormality developed in LV segments corresponding to ECG STE in all
      patients. Coronary arteriography (within 1 week of the index DSE) showed severe
      luminal narrowing in the major epicardial coronary artery supplying the region
      with DSE STE and ischemia (90% to 99% in 9 patients [32%] and 100% in 19 patients
      [68%]). The ischemic region was supplied by ipsilateral (n = 4 [14%]),
      contralateral (n = 21 [75%]), or both ipsilateral and contralateral (n = 3 [11%])
      collateral branches. In conclusion, dobutamine-induced ECG STE in LV segments
      with normal baseline wall motion is a highly reliable marker of viable collateral
      dependent myocardium.

PMID- 23866735
TI  - Down-regulation of miR-181c in imatinib-resistant chronic myeloid leukemia.
AB  - The association of microRNA alterations with progression and treatment outcome
      has been revealed in different types of cancers. To find miRNAs involved in
      imatinib response we performed miRNA microarray followed by RT-qPCR verification
      of 9 available diagnostic bone marrow core biopsies from 9 CML patients including
      4 imatinib-resistant and 5 imatinib-responder patients. Only one differentially
      expressed miRNA, miR-181c, was found when the imatinib-resistant group was
      compared with imatinib-responders. Significant down-regulation of miR-181c in
      imatinib-resistant versus imatinib-responders was confirmed by qRT-PCR. Some miR
      181c target genes such as PBX3, HSP90B1, NMT2 and RAD21 have been associated with
      drug response. 

PMID- 23866737
TI  - Differences between older and younger adults with borderline personality disorder
      on clinical presentation and impairment.
AB  - BACKGROUND: Borderline Personality Disorder (BPD) is well-known to be a
      clinically severe and impairing diagnosis. Research shows that BPD symptoms
      decrease in severity over time. However, a subset of patients with BPD continue
      to meet criteria for the disorder in older adulthood. Little is known about this
      subset. Perception of BPD as a young-person's diagnosis could lead to under
      recognition in older patients. As such, the objective of the present report is to
      provide the first direct comparison between older and younger adults with BPD on
      demographics, clinical presentation, and functional impairment. METHOD: Over 3000
      psychiatric outpatients were evaluated with semi-structured diagnostic
      interviews. Forty-six older adults (age 45-68) and 97 younger adults (age 18-25)
      met criteria for BPD. RESULTS: Both groups reported high levels of functional
      impairment and Axis I comorbidity. Older adults were more likely to endorse
      chronic emptiness, and less likely to endorse impulsivity, self-harm, and
      affective instability. Older adults also reported fewer substance use disorders,
      more lifetime hospitalizations and higher social impairment. CONCLUSION: Older
      adults with BPD had a significantly different clinical presentation from younger
      adults with BPD, including differences in likelihood of endorsing specific BPD
      criteria, social impairment, and comorbid substance use. It is important to
      assess less prototypic features of BPD to avoid overlooking borderline
      personality features in this population.

PMID- 23866736
TI  - Tolerability and safety of artesunate-amodiaquine and artemether-lumefantrine
      fixed dose combinations for the treatment of uncomplicated Plasmodium falciparum
      malaria: two open-label, randomized trials in Nimba County, Liberia.
AB  - BACKGROUND: Safety surveillance of widely used artemisinin-based combination
      therapy (ACT) is essential, but tolerability data in the over five years age
      group are largely anecdotal. METHODS: Two open-label, randomized trials were
      conducted in Nimba County, Liberia: i) the main tolerability trial with 1,000
      Plasmodium falciparum malaria patients aged over five years (Study-T), and, ii)
      an efficacy trial with a secondary objective of collecting tolerability data
      among 300 children age six to 59 months (Study-E). In both studies patients were
      randomized to fixed-dose artesunate-amodiaquine (ASAQ Winthrop(r)) or artemether
      lumefantrine (AL, Coartem(r)), respectively. Clinical- and laboratory-adverse
      events (AEs) were recorded until day 28. RESULTS: Study-T: most patients
      experienced at least one AE. Severe AEs were few, primarily asymptomatic blood
      system disorders or increased liver enzyme values. No treatment or study
      discontinuation occurred. Mild or moderate fatigue (39.8% vs 16.3%, p < 0.001),
      vomiting (7.1% vs 1.6%, p < 0.001), nausea (3.2% vs 1.0%, p = 0.01), and anaemia
      (14.9% vs 9.8%, p = 0.01) were more frequently recorded in the ASAQ versus AL
      arm. Study-E: mild or moderate AEs were common, including anaemia, fatigue,
      vomiting or diarrhoea. The few severe events were asymptomatic blood system
      disorders and four clinical events (pneumonia, malaria, vomiting and stomatitis).
      CONCLUSION: Both ASAQ and AL were well tolerated in patients of all age groups.
      No unexpected AEs occurred. Certain mild or moderate AEs were more frequent in
      the ASAQ arm. Standardised safety surveillance should continue for all forms of
      ACT. TRIAL REGISTRATION: The protocols were registered with Current Controlled
      Trials, under the identifier numbers ISRCTN40020296, ISRCTN51688713,
      (http://www.controlled-trials.com).

PMID- 23866738
TI  - Participation in a 10-week course of yoga improves behavioural control and
      decreases psychological distress in a prison population.
AB  - BACKGROUND: Yoga and meditation have been shown to be effective in alleviating
      symptoms of depression and anxiety in healthy volunteers and psychiatric
      populations. Recent work has also indicated that yoga can improve cognitive
      behavioural performance and control. Although there have been no controlled
      studies of the effects of yoga in a prison population, we reasoned that yoga
      could have beneficial effects in a setting where psychosocial functioning is
      often low, and the frequency of impulsive behaviours is high. METHODS:
      Participants were recruited from 7 British prisons and randomly allocated to
      either a 10-week yoga programme (yoga group; 1 class per week; N = 45) or a
      control group (N = 55). Self-report measures of mood, stress, and psychological
      distress were collected before and after the intervention period. Participants
      completed a cognitive-behavioural task (Go/No-Go) at the end of the study, which
      assessed behavioural response inhibition and sustained attention. RESULTS:
      Participants in the yoga group showed increased self-reported positive affect,
      and reduced stress and psychological distress, compared to participants in the
      control group. Participants who completed the yoga course also showed better
      performance in the cognitive-behavioural task, making significantly fewer errors
      of omission in Go trials and fewer errors of commission on No-Go trials, compared
      to control participants. CONCLUSIONS: Yoga may be effective in improving
      subjective wellbeing, mental health, and executive functioning within prison
      populations. This is an important consideration given the consistently high rates
      of psychological morbidity in this group and the need for effective and
      economical intervention programmes.

PMID- 23866740
TI  - Challenges for nursing education in Angola: the perception of nurse leaders
      affiliated with professional education institutions.
AB  - BACKGROUND: Angola is one of the African countries with the highest morbidity and
      mortality rates and a devastating lack of human resources for health, including
      nursing. The World Health Organization stimulates and takes technical cooperation
      initiatives for human resource education and training in health and education,
      with a view to the development of countries in the region. The aim in this study
      was to identify how nurses affiliated with nursing education institutions
      perceive the challenges nursing education is facing in Angola. METHODS: After
      consulting the National Directory of Human Resources in Angola, the nurse leaders
      affiliated with professional nursing education institutions in Angola were
      invited to participate in the study by email. Data were collected in February
      2009 through the focus group technique. The group of participants was focused on
      the central question: what are the challenges faced for nursing education in your
      country? To register and understand the information, besides the use of a
      recorder, the reporters elaborated an interpretative report. Data were coded
      using content analysis. RESULTS: Fourteen nurses participated in the meeting,
      most of whom were affiliated with technical nursing education institutions. It
      was verified that the nurse leaders at technical and higher nursing education
      institutions in Angola face many challenges, mainly related to the lack of
      infrastructure, absence of trained human resources,bureaucratic problems to
      regularize the schools and lack of material resources. On the opposite, the
      solutions they present are predominantly centered on the valuation of nursing
      professionals, which implies cultural and attitude changes. CONCLUSIONS: Public
      health education policies need to be established in Angola, including action
      guidelines that permit effective nursing activities. Professional education
      institutions need further regularizations and nurses need to be acknowledged as
      key elements for the qualitative enhancement of health services in the country.

PMID- 23866739
TI  - Are structural brain abnormalities associated with suicidal behavior in patients
      with psychotic disorders?
AB  - Suicide represents a major health problem world-wide. Nevertheless, the
      understanding of the neurobiological underpinnings of suicidal behavior remains
      far from complete. We compared suicide attempters to non-attempters, and high vs.
      low lethality attempters, to identify brain regions associated with suicidal
      behavior in patients with psychotic disorders. 489 individuals with
      schizophrenia, schizoaffective disorder, or psychotic bipolar disorder I and 262
      healthy controls enrolled in the B-SNIP study were studied. Groups were compared
      by attempt history and the highest medical lethality of previous suicide
      attempts. 97 patients had a history of a high lethality attempt, 51 of a low
      lethality attempt and 341 had no attempt history. Gray matter volumes were
      obtained from 3T structural MRI scans using FreeSurfer. ANCOVAs were used to
      examine differences between groups, followed by Hochberg multiple comparison
      correction. Compared to non-attempters, attempters had significantly less gray
      matter volume in bilateral inferior temporal and superior temporal cortices, left
      superior parietal, thalamus and supramarginal regions, right insula, superior
      frontal and rostral middle frontal regions. Among attempters, a history of high
      lethality attempts was associated with significantly smaller volumes in the left
      lingual gyrus and right cuneus. Compared to non-attempters, low lethality
      attempters had significant decreases in the left supramarginal gyrus, thalamus
      and the right insula. Structural brain abnormalities may distinguish suicide
      attempters from non-attempters and high from low lethality attempters among
      individuals with psychotic disorders. Regions in which differences were observed
      are part of neural circuitries that mediate inhibition, impulsivity and emotion,
      visceral, visual and auditory perception. 

PMID- 23866741
TI  - [Conducting scientific research on drinking-water and advocating reasonable
      drinking for children].

PMID- 23866742
TI  - [Daily intake of plain water and beverages of primary and middle school students
      in four cities of China].
AB  - OBJECTIVE: To describe the daily consumption of plain water and beverages of
      primary and middle school students in four cities of China. METHODS: A total of
      5914 students from Beijing, Shanghai, Guangzhou and Chengdu were selected using
      multiple-stage random sampling method, and 5868 students completed the study from
      September to October 2011. The information on amounts and types of drinking water
      was recorded using a 24 hour measurement for seven consecutive days. The amount
      of plain water and beverages was analyzed for subjects in different gender,
      grades and cities. RESULTS: The daily consumption of plain water of subjects was
      (744 +/- 484) ml (68.3% of total drinking water) with statistically significant
      difference among the Guangzhou, Beijing, Shanghai and Chengdu ((869 +/- 528),
      (818 +/- 518), (702 +/- 471), and (573 +/- 333) ml; F = 113.74, P < 0.05). The
      amount of plain water in boys (809 +/- 534) ml was significantly higher than in
      girls (683 +/- 436) ml (Z = 9.58, P < 0.05) while higher in urban (792 +/- 531)
      ml than in rural (695 +/- 427) ml (Z = -6.09, P < 0.05). The consumption of plain
      water in high school students was the highest (829 +/- 513) ml, and that in
      primary students was the lowest (672 +/- 426) ml (F = 55.23, P < 0.05). The
      average daily consumption of beverages was (345 +/- 287) ml (31.7% of total
      drinking water) and the highest in Shanghai (424 +/- 304) ml, then in Beijing
      (347 +/- 303) ml and in Guangzhou (316 +/- 267) ml, the lowest in Chengdu (293 +/
      255) ml (F = 58.94, P < 0.05). The consumption of beverages for students in
      urban areas (394 +/- 301) ml was higher than that in rural areas (296 +/- 264) ml
      (Z = -14.48, P < 0.05), but no significant difference between boys (348 +/- 306)
      ml and girls (342 +/- 269) ml (Z = -1.44, P > 0.05). The consumption of beverages
      of high school students (356 +/- 309) ml and middle school students (360 +/- 301)
      ml were higher than primary school students (328 +/- 263) ml (F = 8.37, P <
      0.05). CONCLUSION: The major drinking water of primary and middle school students
      in four cities of China was plain water. The amounts of consumption of plain
      water and beverages varied in different cities, urban and rural and levels of
      education.

PMID- 23866743
TI  - [The relationship between within-day drinking occasion and intake amount of water
      of primary and middle school students in four cities of China].
AB  - OBJECTIVE: To investigate the number of drinking occasions per day and average
      amount consumed per drinking occasion of primary and middle school students in
      four cities of China, and understand the relationship among drinking occasion,
      average amount consumed per drinking occasion and total drinking water. METHODS:
      A total of 5914 primary and middle school students from Beijing, Shanghai,
      Guangzhou and Chengdu were selected using multiple-stage random sampling method,
      and 5868 students completed the study from September to October in 2011. The
      detailed information of amounts and types of daily drinking water was recorded by
      subjects using a 24 hours measurement for seven consecutive days. Analysis of the
      relationship among drinking occasion, average amount consumed per drinking
      occasion and total drinking water was carried out. RESULTS: The daily total
      drinking water of subjects was (1089 +/- 540) ml; the daily number of drinking
      occasions was (4.7 +/- 1.8) times, with 79.1% (4639/5868) of subjects reporting 6
      or less drinking occasions. The amount consumed per drinking occasion was (239 +/
      96) ml, plain water (231 +/- 112) ml, and beverages (237 +/- 112) ml. The number
      of drinking occasions of subjects was positively correlated with total drinking
      water (r = 0.614, P < 0.05), and negatively correlated with the average amount
      consumed per drinking occasion (r = -0.211, P < 0.05). Total drinking water and
      the average amount consumed per drinking occasion was positively correlated (r =
      0.598, P < 0.05). CONCLUSION: The number of drinking occasion of primary and
      middle school students more than 6 times was fewer in four cities of China, but
      the average amount of beverages consumed per drinking occasion was relatively
      more. With the increasing of drinking occasion, the average amount consumed per
      drinking occasion decreased, but total drinking water increased.

PMID- 23866744
TI  - [Water intake of primary and middle school students in four cities of China].
AB  - OBJECTIVE: To investigate total intake of drinking water of primary and middle
      school students in four cities of China, and to provide scientific evidence for
      developing standard of intake of drinking water for primary and middle school
      students in China. METHODS: A total of 5914 primary and middle school students
      were selected from Beijing, Shanghai, Chengdu and Guangzhou using multi-stage
      random sampling method and 5868 subjects completed the survey. The information on
      the amounts of daily drinking water was recorded for seven consecutive days using
      a 24 hour measurement. The amounts of daily drinking water among different cities
      and ages and between boys and girls or urban and rural were analyzed. RESULTS:
      The average daily total drinking water of subjects was (1089 +/- 540) ml, with
      significant differences among the four cities ((1165 +/- 549), (1126 +/- 544),
      (866 +/- 421), (1185 +/- 568) ml in Beijing, Shanghai, Chengdu and Guangzhou,
      respectively; F = 114.28, P < 0.05). The average daily drinking water was
      significantly higher in boys (1157 +/- 575) ml than in girls (1026 +/- 498) ml (Z
      = 8.88, P < 0.05), and in urban (1185 +/- 578) ml than in rural (991 +/- 480) ml
      (Z = 13.94, P < 0.05). The difference among different ages was statistically
      significant (F = 91.53, P < 0.05) with ascending order in 7 - 10, 11 - 13 and 14 
      17 years old ((953 +/- 483), (1134 +/- 551) and (1170 +/- 557) ml respectively).
      CONCLUSION: The daily consumption of total drinking water is different in primary
      and middle school students among different cities, regions, genders and ages.

PMID- 23866745
TI  - [Drinking in different periods of a day of primary and middle school students in
      four cities of China].
AB  - OBJECTIVE: To investigate intake of water in different periods of a day of
      primary and middle school students in Beijing, Shanghai, Guangzhou and Chengdu of
      China. METHODS: A total of 5914 primary and middle school students from Beijing,
      Shanghai, Guangzhou and Chengdu were recruited using multiple-stage random
      sampling method from September to October 2011. Among them, 5868 students
      completed the survey. The information of amounts and types of drinking in 8 time
      periods, morning, afternoon, night as well as in meal and non-meal time in 24
      hours of a day was recorded by subjects for seven consecutive days using a
      quantitative measurement. This information was analyzed by different periods.
      RESULTS: The amount of drinking water among 8 periods of a day was (99 +/- 101),
      (130 +/- 106), (191 +/- 155), (96 +/- 107), (246 +/- 172), (90 +/- 101), (188 +/-
      135) and (50 +/- 81) ml, respectively for before breakfast, during breakfast,
      after breakfast, during lunch, after lunch, during dinner, after dinner, and
      midnight (F = 1679.77, P < 0.01). Based on three periods of a day, the amount of
      drinking water in the morning (420 +/- 242) ml was the statistically
      significantly most, followed by afternoon (341 +/- 199) ml, and the least in the
      evening (327 +/- 195) ml (F = 325.23, P < 0.01). The distribution trend of plain
      water in three periods was the same as total drinking water, with (270 +/- 209),
      (250 +/- 179) and (224 +/- 177) ml, respectively (F = 84.89, P < 0.01) ; but
      beverage consumption was the most in the morning(151 +/- 133) ml, then in the
      evening (103 +/- 122) ml, and the least in the afternoon (91 +/- 199) ml (F =
      373.56, P < 0.01). The daily plain water consumption in meal time was (316 +/-
      247) ml, while it in non-meal time was (773 +/- 445) ml with statistically
      significant difference (Z = 65.2, P < 0.01). There was no significant difference
      in meal time between plain water (165 +/- 194) ml and beverage (151 +/- 152) ml
      (Z = 0.59, P = 0.56) whilst plain water (579 +/- 408) ml in non-meal time was
      significantly higher than beverages (194 +/- 204) ml (Z = 64.5, P < 0.01).
      CONCLUSION: The amount of drinking water of primary and middle school students in
      different periods of a day was different in four cities of China.

PMID- 23866746
TI  - [The impact of water level changes on the Oncomelania snail habitats in Poyang
      Lake regions before and after the impoundment of Three Gorges reservoir].
AB  - OBJECTIVE: To explore the impact of the impoundment of Three Gorges reservoir on
      Oncomelania snail habitats of Poyang Lake. METHODS: Four counties with
      schistosomiasis endemic around the Poyang Lake, naming as Xingzi, Duchang,
      Jinxian and Xinjian, were selected as study areas. The average daily water level
      of four major hydrological stations near the above 4 counties from 1997 to 2008
      were collected, as well as the elevation of 215 marshlands with snails in those 4
      counties, the data of schistosomiasis endemic situation and snail survey of 4
      counties in the year before the impoundment of Three Gorges reservoir (2002) and
      the 6th year after the impoundment of Three Gorges reservoir (2008). The
      fluctuations of water levels of Poyang Lake, flooding day of marshland with
      snails as well as the changes of the indicators in snail survey and prevention
      and control measures before and after the impoundment of Three Gorges reservoir
      were compared. RESULTS: Before the impoundment of Three Gorges reservoir, the
      fluctuations of average water level of the four hydrological stations around
      Poyang Lake was 6.91-12.93 m; which reduced to 5.72 - 10.75 m after the
      impoundment. The D-value of the fluctuations of average water level was (1.06 +/-
      0.47) m. The date of the annual maximum water level delayed by an average of 12
      d; while the date of annual minimum water level arrived an average of 12 d
      earlier than the impoundment of Three Gorges reservoir. The average flooding days
      of marshland with snails were separately (100.04 +/- 42.06) d before the
      impoundment and (64.13 +/- 22.30) d after the impoundment. The difference was
      statistically significant (t = 3.70, P < 0.05). The density of snails in the 4
      counties around Poyang Lake was 0.8437/0.1 m(2) after the impoundment; declining
      by 31.04% from the snail density (1.2234/0.1 m(2)) before the impoundment. The
      density of infectious snails was 0.0014/0.1 m(2) after the impoundment; dropping
      by 67.34% from it (0.0042/0.1 m(2)) before the impoundment; the infection rate of
      snails was separately 0.34% after the impoundment and 0.16% before the
      impoundment. The difference was statistically significant (chi(2) = 53.25, P <
      0.05). The coverage rate of chemotherapy increased from 4.45% (35 558/798 200) in
      2002 to 9.80% (79 457/810 400) in 2008; the difference was statistically
      significant (chi(2) = 17 336.63, P < 0.05). The coverage rate of snail killing
      increased from 1.35% (389.04/28 824.66) in 2002 to 7.49% (2260.90/30 166.22) in
      2008; the difference was also statistically significant (chi(2) = 28 824.66, P <
      0.05). CONCLUSION: The impact of the impoundment of Three Gorges reservoir
      shortened the flooding days of marshland with snails and helped the prevention
      and control of schistosomiasis in Poyang Lake regions as the environment went
      against the breeding of the snails.

PMID- 23866747
TI  - [Survey on seroepidemiological status and vaccine coverage of hepatitis B among
      children in Chaoyang district of Beijing in 2010].
AB  - OBJECTIVE: To explore seroepidemiological status and vaccine coverage of
      hepatitis B in children aging under 15 years old in Chaoyang district of Beijing.
      METHODS: A total of 1602 children aging under 15 years old, residents or floating
      population who had lived here more than six months, were randomly selected by
      multistage cluster sampling, from Chaoyang district of Beijing in year 2010. The
      demographic information and vaccine coverage of hepatitis B vaccine (HepB) were
      collected by self-designed questionnaire.5 ml blood was collected from each
      subject and the serum HBsAg, anti-HBs and anti-HBc were detected by Abbott
      microparticle enzyme-linked immunoassay. Those whose HBsAg was positive were then
      tested HBeAg and anti-HBe. The positive rate of hepatitis B indicators and
      coverage rate of HepB in different population were compared. RESULTS: The
      positive rate of HBsAg, anti-HBs and anti-HBc were 0.56% (9/1602), 64.17%
      (1028/1602) and 2.12% (34/1602), respectively; while the age standardized rates
      were separately 0.57%, 66.36% and 1.98%; and the gender-adjusted rates were
      0.56%, 64.23% and 2.12% respectively. The positive rate of anti-HBs was
      statistically significant (chi(2) = 165.445, P = 0.000). The positive rate of
      anti-HBs was up to 90.73% (235/259) among 1-2 years old children, followed by
      76.22% (141/185) among 13 - 15 years old children, 67.21% (166/247) among 3 - 4
      years old children, 61.22% (150/245) among 9 - 10 years old children, 60.68%
      (142/234) among 11 - 12 years old children, 49.05% (103/210) among 5 - 6 years
      old children and 40.99% (91/222) among 7 - 8 years old children. The average
      coverage rate of HepB was 90.44% (1371/1516), separately 93.76% (661/705) in
      residents and 87.55% (719/811) in floating population. The difference was
      statistically significant (chi(2) = 16.829, P = 0.000). CONCLUSION: HBsAg
      positive rate in children under 15 years old in Chaoyang district of Beijing
      dropped to less than 1% and the coverage rate of HepB had reached over 90%. It is
      suggested that we should pay more attention to increase the coverage rate of HepB
      among floating children under 15 years old.

PMID- 23866748
TI  - [Gender and its impact on condom use among HIV male serodiscordant couples].
AB  - OBJECTIVE: To study the gender-based factors which influence the condom use among
      the HIV serodiscordant couples in selected regions of China. METHODS: Based on
      the analysis of the existing case reporting database and convenient sampling in
      the cross-sectional study, a total of 481 female HIV-negative spouses completed
      an interviewer-administered questionnaire regarding demographic characters, the
      knowledge, behaviors and the gender-based factors in five sites of four provinces
      Sichuan (Zhaojue), Yunnan (Dali), Henan (Weishi) and Guangxi (Lingshan and
      Luzhai), during June-September 2011. chi(2) analysis and logistic regression were
      used to study the gender-based factors influencing condom use among the
      participants. RESULTS: Among the 481 female HIV-negative spouses, the average age
      was (35.1 +/- 6.7) years, and the proportion of Han and Yi nationality were high,
      43.5% (209/481) and 41.8% (201/481), respectively. The awareness of knowledge
      related to HIV spousal transmission was high (>= 79.6%). A total of 86.9%
      (418/481) used condom more frequently after informed the status of HIV infection
      of their spouses, and the condom use consistency was 56.6% (272/481). A total of
      57.6% (277/481) reported low sexual relationship power; 34.5% (166/481)
      experienced forced sex in the past 1 year. And the proportion of condom use self
      efficacy from 0 to 3 scores were 12.7% (61/481), 23.9% (115/481), 8.7% (42/481)
      and 54.7% (263/481), respectively (median = 3). Han and other nationality were
      significantly more likely to use condom consistently than Yi, with odds ratio
      (95%CI) of 0.01 (0.00 - 0.03) and 0.01 (0.00 - 0.04), and the female spouses with
      higher condom use self-efficacy used condom more consistently than the lower
      ones, with odds ratio (95%CI) of 0.20(0.11 - 0.34). CONCLUSION: The female
      spouses with higher condom use self-efficacy were more likely to use condom
      consistently after excluding the confounding effect of nationality.

PMID- 23866749
TI  - [The application of network scale-up method on female sex workers and clients
      size estimation in Taizhou city].
AB  - OBJECTIVE: To estimate the size of female sex workers and clients in Taizhou
      city. METHODS: A household survey using network scale-up method (NSUM) was
      conducted among the 3000 community residents in Taizhou city from August to
      October in 2011, which aimed to estimate the social network size (c value) of
      Taizhou residents, and the c value was adjusted by demographic characteristics,
      back estimation and outlier elimination. Using the adjusted c value, the number
      of acquaintance of female sex workers or clients and the respect level toward
      female sex workers or clients were used to estimate the size of female sex
      workers and clients. RESULTS: A total of 2783 valid questionnaires were
      collected, among which 1380 (49.6%) were collected from Taixing city, 1403
      (50.4%) were collected from Jingjiang city. 1334 respondents were male (47.9%)
      and 1449 (47.9%) respondents were female. The mean age was (39.4 +/- 10.7) years.
      The average personal social network size using original data for Taizhou
      residents was 525, which differed from place, sex, age, educational level and
      marriage status. Using the remaining known populations through back estimation,
      the social network size was 419 and became 424 after the elimination of outliers.
      The estimated population size for female sex worker was 6370 (95%CI: 5886 -
      6853), which accounted for 0.52% (6370/1 229 980) of the total number of female
      aged from 15 to 49. The estimated population size for clients was 15 202 (95%CI:
      14 560 - 15 847), which accounted for 1.28% (15 202/1 190 340) of the total
      number of males aged from 15 to 49 and the ration of clients to female sex worker
      was 2.39:1. CONCLUSION: NSUM is an easy and quick way to estimate the size of
      female sex workers or clients, but the estimated sizes are subject to bias and
      error due to estimate effect and sample representativeness.

PMID- 23866750
TI  - [Correlation of resistance to peer pressure and risky decision-making with
      adolescent health risk behaviors].
AB  - OBJECTIVE: To explore possible interrelationships among resistance to peer
      pressure, risky decision-making and health risk behaviors among young
      adolescents. METHODS: Based on the cluster sampling method, the participants who
      were recruited from 5 junior middle schools in Guangzhou and 3 junior middle
      schools in Shenyang city on October, 2010, were administered to complete the
      questionnaire concerned with their experiences with drinking and smoking during
      the past 30 days preceding the survey, and the hours using computer daily both in
      weekdays and in weekend. The level of resistance to peer influence and risky
      decision-making were assessed by Resistance to peer influence scale (RPIS) and
      Youth decision-making questionnaire (YDMQ). Logistic regression was used to
      explore possible interrelationships among resistance to peer influence, risky
      decision-making and health risk behaviors among young adolescents. RESULTS: A
      total of 1985 questionnaires were valid, including 1001(50.4%) boys and 984
      (49.6%) girls. About 27.1% (537/1985) junior middle school students reported
      having health risk behaviors, boys' (30.7%, 307/1001) was higher than girls'
      (23.4%, 230/984) with significant gender difference (P < 0.05). The prevalence of
      smoking, drinking during the past 30 days before the survey and using computer
      over 3 hours daily in weekdays and in weekend were 5.1% (102/1985), 14.3%
      (284/1985), 3.5% (70/1985) and 13.7% (272/1985), respectively. The rate of
      drinking, using computer over 3 hours daily in weekdays and in weekend were
      higher in males (16.4% (164/1001), 4.5% (45/1001), 16.2% (162/1001)) than those
      in females (12.2% (120/984), 2.5% (25/984), 11.2% (110/984)) (P < 0.05). The
      scores of RPIS and YDMQ of the two cities adolescents were 2.82 +/- 0.39 and 1.68
      +/- 0.62. The students reported smoking, drinking during the past 30 days before
      the survey and using computer over 3 hours daily in weekend gained lower RPIS
      scores (2.43 +/- 0.40, 2.61 +/- 0.41, 2.77 +/- 0.40) than their counterparts who
      didn't report these kind of health risk behaviors (2.84 +/- 0.38, 2.85 +/- 0.38,
      2.82 +/- 0.39)(P < 0.05). And those reported smoking, drinking during the past 30
      days before the survey and using computer over 3 hours daily in weekdays and in
      weekend gained higher YDMQ scores (2.38 +/- 0.66, 2.06 +/- 0.66, 1.97 +/- 0.72,
      1.84 +/- 0.64, respectively) than their counterparts who didn't report these kind
      of health risk behaviors (1.64 +/- 0.38, 1.61 +/- 0.58, 1.67 +/- 0.61, 1.65 +/-
      0.61, respectively) (P < 0.05). After adjusting gender, area, parental education
      degree, self-reported family economic condition, multi-variant logistic
      regression analysis indicated that the low and middle level of resistance to peer
      influence (low and middle level vs high level, had odds ratios of 2.97 (1.96 -
      4.50) and 1.51 (1.05 - 2.16)), and also the middle and high level of risky
      decision-making (middle and high level vs low level, had odds ratios of 1.62
      (1.19 - 2.22) and 3.43 (2.39 - 4.90)) were all the risk factors of adolescent
      health risk behaviors. CONCLUSION: Adolescents with poor ability of resistance to
      peer pressure and high risky decision-making were both the risk factors of
      adolescent health risk behaviors.

PMID- 23866751
TI  - [Impact of maternal weight gain during pregnancy on the risk of infant obesity].
AB  - OBJECTIVE: To study the impact of maternal weight gain during pregnancy on the
      risk of infant obesity within 1 year old. METHODS: A total of 785 infants who
      were born in Hefei and participated children medical care in one district health
      center and their mothers were chosen as the research subjects from September 2010
      to September 2011. Three groups were classified by weight gain during pregnancy
      according to the percentiles: excessive pregnancy weight gain group of 126 pairs,
      adequate pregnancy weight gain group of 542 pairs and inadequate pregnancy weight
      gain group of 117 pairs. Mother's general demographic information was collected.
      The height and weight were measured when the infant was 42 days, 3, 6, 9, and 12
      months of physical examination. Z score was calculated. The differences of Z
      score in different groups were compared and the RR values of different weight
      gain during pregnancy on infant obesity were computed. RESULTS: The weight-for
      age Z score (WAZ) of infant at 42 days 3, 6, 9 and 12 months in excessive
      pregnancy weight gain group were 0.23 +/- 0.93, 0.25 +/- 1.03, 0.23 +/- 0.99,
      0.28 +/- 1.09, 0.26 +/- 1.14, respectively, all higher than that of the
      corresponding age in adequate pregnancy weight gain group (-0.04 +/- 1.02, -0.07
      +/- 0.99, -0.05 +/- 0.98, -0.06 +/- 0.97, -0.07 +/- 0.95, respectively). The
      differences were statistically significant (all P values < 0.05). In excessive
      pregnancy weight gain group, infant body mass index (BMI) at 9 months ((18.01 +/-
      0.15) kg/m(2)) and 12 months ((17.66 +/- 0.15) kg/m(2)) were higher than that of
      adequate pregnancy weight gain group ((17.63 +/- 0.13) and (17.22 +/- 0.15)
      kg/m(2), respectively). The differences were statistically significant (all P
      values < 0.05). Differences of infant Height-for-age Z score (HAZ) among three
      groups were not statistically significant (all P values > 0.05). Compared to
      adequate pregnancy weight gain group, RR (95%CI) value of infant obesity in
      excessive pregnancy weight gain group was 1.86 (1.14 - 3.03). CONCLUSION:
      Excessive maternal weight gain during pregnancy increased the risk of infant
      obesity within 1 year old.

PMID- 23866752
TI  - [Survey on the occupational musculoskeletal disorder and its risk factors among
      male steelworkers].
AB  - OBJECTIVE: To study the prevalence of occupational musculoskeletal disorders
      (OMSD) of male steelworkers and explore its occupational and individual risk
      factors. METHODS: 1620 male workers from a steel mill were selected as subjects
      through random cluster sampling in 2010. A revised Nordic Musculoskeletal
      disorder standard questionnaire and a questionnaire from National Institute for
      Occupational and Health of the Netherlands were used to ask and record the OMSD
      and its risk factors. The questionnaires were filled in by the workers. Annual
      prevalence of OMSD in different parts of the body were counted according to
      different age, working years and educational level, logistic regression was used
      to analyze its influence factors. RESULTS: OMSD in these workers primarily
      located in waist, neck and shoulders, annual prevalence were 51.0% (825), 48.5%
      (785) and 37.7% (610) respectively. Annual prevalence of other body parts were
      28.0% (454) for back, 23.6% (383) for knee, 21.0% (341) for wrist, 17.9% (290)
      for ankle/foot, 14.1% (229) for elbow and 12.7% (205) for coxa. The annual
      prevalence of OMSD for each part tended to increase with age, mainly in waist and
      neck. Of the different age groups <= 24, 25 - 29, 30 - 34, 35 - 39, 40 - 44, 45 -
      49, >= 50, the annual prevalence in waist was 26.4% (43/163), 37.8% (71/188),
      52.8% (162/307), 55.6% (160/288), 53.8% (99/184), 55.9% (80/143), 61.6% (204/331)
      respectively (chi(2) = 72.5, P < 0.05); correspondingly, the annual prevalence in
      neck was 22.7% (37/163), 40.4% (76/188), 50.2% (154/307), 48.6% (140/288), 56.0%
      (103/184), 53.1% (76/143), 57.7% (191/331) respectively (chi(2) = 65.3, P <
      0.05). The annual prevalence of OMSD increased with the working years. Of the
      different working years groups <= 4, 5 - 9, 10 - 14, 15 - 19, 20 - 24, 25 - 29,
      >= 30, the annual prevalence in waist was 30.2% (85/281), 46.2% (66/143), 56.4%
      (162/287), 56.8% (137/241), 50.6% (78/154), 59.2% (90/152), 60.7% (173/285)
      respectively (chi(2) = 71.3, P < 0.05);correspondingly, the annual prevalence in
      neck was 28.8% (81/281), 49.0% (70/143), 52.6% (151/287), 50.2% (121/241), 51.9%
      (80/154), 53.9% (82/152), 59.3% (169/285) respectively (chi(2) = 61.5, P < 0.05).
      The annual prevalence of OMSD decreased with education level. Of the different
      groups of education level (junior high school level and below, senior high school
      level, university level or above), the OMSD prevalence in waist was 61.5%
      (176/286), 61.9% (359/692), 44.2% (272/615) respectively (chi(2) = 26.0, P <
      0.05);correspondingly, the annual prevalence in neck was 56.3% (161/286), 50.0%
      (346/692), 42.3% (260/615)respectively (chi(2) = 21.2, P < 0.05). Univariate
      logistic regression showed that the work load factors such as the working years
      >= 30 (OR = 3.562, 95%CI: 2.514 - 5.046), maintain substantial stoop for a long
      time (OR = 2.003, 95%CI: 1.612 - 2.488), often stooping with vast scale (OR =
      1.897, 95%CI: 1.557 - 2.312), and torso repeating same action many times per
      minute (OR = 1.870, 95%CI: 1.529 - 2.288) could increase the annual prevalence of
      OMSD in waist most likely (P < 0.05). The working years >= 30 (OR = 3.597, 95%CI:
      2.535 - 5.105), neck leaning forward (OR = 2.455, 95%CI: 2.010-2.99), neck
      leaning back (OR = 1.999, 95%CI: 1.569 - 2.546), and neck rotation (OR = 2.381,
      95%CI: 1.907 - 2.972) were main risk factors causing OMSD in neck (P < 0.05).
      CONCLUSION: The most serious musculoskeletal disorders of male steelworkers were
      waist and neck pain. Personal factors such as age, working years, work load
      factors such as harmful working postures, manual heavy lifting, and labour
      organizational factors such as work overtime were the main risk factors of
      musculoskeletal disorders to the male steelworkers.

PMID- 23866753
TI  - [Analysis of blood lead level and its influencing factors of workers in one lead
      acid storage cell enterprise].
AB  - OBJECTIVE: To understand the blood lead level and its influencing factors of
      workers in one lead acid storage cell enterprise in Jiangsu Province. METHODS: An
      occupational health field investigation was done to this storage cell enterprise
      at the end of June 2011 to measure the air lead fume (dust) concentration of
      workplaces. Health-care information of 1364 person-times from 2009 - 2011 was
      collected, including blood lead level, general state of health, life and health
      habit. One way ANOVA and ordinal multi-categorical logistic stepwise regression
      were used to analysis the influencing factors of blood lead level. RESULTS: The
      lead fume concentration range was 0.008-0.354 mg/m(3) among 12 measuring points,
      which 7 places were unqualified, while the concentration range of lead dust was
      0.023 - 2.432 mg/m(3), 24 out of 27 measuring places were unqualified, both the
      qualified rate were low. The blood lead concentration of objects was (259.54 +/-
      106.62) ug/L, among which 96 people (7.04%) who >= 400 ug/L should be identified
      as suspected "observation object", blood lead concentration >= 600 ug/L was not
      found. The blood lead concentration of male (279.76 +/- 114.93 ug/L) was
      significantly higher than female (242.44 +/- 95.86) ug/L (t = 6.441, P < 0.01).
      The proportion of >= 400 ug/L in male (11.04%, 69/625) was significantly higher
      than female (3.65%, 27/739) (chi(2) = 28.237, P < 0.01). The blood lead
      concentration of workers who exposed to lead fume or dust (265.93 +/- 103.70)
      ug/L was significantly higher than those of not exposed to lead (205.30 +/-
      115.62) ug/L (t = -6.037, P < 0.01), the blood lead concentration of workers who
      exposed to lead dust was (267.38 +/- 98.02) ug/L significantly higher than those
      of exposed to lead fume (260.81 +/- 121.80) ug/L (t = -2.408, P < 0.05). The
      proportion of >= 400 ug/L in workers who exposed to lead fume (dust) (7.60%,
      93/1223) was significantly higher than those of not exposed to lead (2.13%,
      3/141) (chi(2) = 4.538, P < 0.05). Ordinal multi-categorical logistic stepwise
      regression found that the lead fume concentration >= 0.03 mg/m(3), lead dust
      concentration >= 0.05 mg/m(3) (OR = 1.59, 95%CI: 1.06 - 2.39), length of service
      >= 3 years (OR = 1.82, 95%CI: 1.12 - 2.98), smoking (OR = 2.06, 95%CI: 1.27 -
      3.37) can increase the level of blood lead concentration. CONCLUSIONS: Lead dust
      concentration of the enterprise exceeded the standard. Workers exposed to lead
      fume (dust) have more occupational health hazard of lead, of whom the blood lead
      concentration was high. Higher lead fume (dust) concentration in workplace,
      longer length of service, smoking were risk factors of high blood lead
      concentration.

PMID- 23866754
TI  - [Effect of comprehensive control and prevention for chronic disease in
      demonstration plot of Chongqing].
AB  - OBJECTIVE: To evaluate the effect of comprehensive control and prevention for
      chronic diseases in demonstration plot of Chongqing. METHODS: Residents were
      enrolled through multi-stage stratified random sampling method from 17 districts
      or counties which had successfully established demonstration plots and 21
      districts or counties which had not established demonstration plots (non
      demonstration plot for short) yet on May, 2012. Questionnaire was designed to
      survey awareness of health knowledge, health behaviors and utilization of health
      supportive tools. The results were analyzed by SPSS 15.0 software. RESULTS: We
      investigated 15 108 residents, 6156 of which were in demonstration plot and
      others (8951) were not. The findings revealed the percentage of the people who
      were aware the national action of health lifestyle in demonstration plot and in
      non-demonstration plot were 44.4% (2734/6157) and 40.2% (3598/8951),
      respectively, and the awareness of the hypertension risk of too much sodium were
      72.4% (4458/6156) and 67.5% (6042/8951), respectively, and the awareness of the
      cardinal vascular disease (CVD) risk of obesity and overweight were 77.2%
      (4753/6157) and 69.6% (6230/8951), respectively. About the residents' health
      behaviors in demonstration plot and in non-demonstration plot, the utilization
      rates of salt restriction scoop or pot were 23.5% (1447/6157) and 17.9%
      (1602/8951), and the utilization rates of oil restriction pot were 16.7%
      (1028/6157) and 11.8% (1064/8951), respectively. Totally, 33 of the 37 indexes
      were shown higher in demonstration plot than that in non-demonstration plot (P <
      0.05). CONCLUSION: The chronic diseases comprehensive control and prevention in
      demonstration plot was more effective, and the remarkable improvement of health
      knowledge and behaviors level had been achieved in demonstration plot.

PMID- 23866755
TI  - [Metabolism of Salmonella enterica serovar typhi influenced by RpoE and RpoS
      under hyperosmosis].
AB  - OBJECTIVE: To study the role of RpoE and RpoS on the influence of the metabolism
      and growth of bacterial under hyperosmotic stress. METHODS: The rpoS/rpoE double
      deletion mutant of Salmonella enterica serovar typhi (S. typhi) was prepared by
      homologous recombination through the suicide plasmid mediated. The recombination
      was visualized by PCR. Growth curves were drawn by using photometric value A600
      as the ordinate and cultivation time as abscissa. The survival abilities of
      bacterial were compared under hyperosmotic stress. Statistical differences of
      early logarithmic growth stage (4 h) and laters logarithmic growth stage (12 h)
      were analyzed by one-way ANOVA. The expression difference of metabolism related
      genes of wild-type and mutant strains of S. Typhi incubated under hyperosmotic
      stress were investigated by Salmonella genomic DNA microarray. Real-time
      quantitative PCR (qRT-PCR) was performed to validate the results of microarray
      assay in some selected genes. RESULTS: The rpoS/rpoE double deletion mutant of S.
      Typhi was successfully generated. The analysis of growth curve showed that the 4
      hour and 12-hour A600 values were separately 0.503 +/- 0.018 and 2.060 +/- 0.112
      in rpoS deletion mutant strains, 0.293 +/- 0.053 and 1.933 +/- 0.115 in rpoE
      deletion mutant strains, and 0.051 +/- 0.007 and 0.963 +/- 0.111 in rpoS/rpoE
      double deletion mutant strains; all of which were lower than the values of wild
      type strains, who were 0.725 +/- 0.097 and 2.496 +/- 0.171, respectively. The
      difference were statistically significant (P < 0.05). The genomic DNA microarray
      revealed that 42 genes relevant with bacterial metabolism were influenced by RpoE
      and RpoS. Results of qRT-PCR showed that the expression values of rpsE, rbsK,
      nusG and etuB in rpoS deletion mutant strains were (1.86 +/- 0.14)*10(6), (1.37
      +/- 0.11)*10(6), (2.72 +/- 0.58)*10(6) and (8.27 +/- 1.01)*10(6) copies/ug,
      respectively; while those in rpoE deletion mutant strains were (2.19 +/-
      0.17)*10(6), (1.51 +/- 0.12)*10(6), (2.73 +/- 0.57)*10(6) and (9.63 +/-
      1.42)*10(6) copies/ug, respectively. Compared with the values in wild-type
      strains, which were separately (1.94 +/- 0.10)*10(6), (1.52 +/- 0.11)*10(6),
      (2.39 +/- 0.52)*10(6) and (10.83 +/- 1.52)*10(6) copies/ug, the differences was
      not statistical significance (P > 0.05). However, compared with the values in
      rpoS/rpoE double mutant strains, which were separately (5.64 +/- 0.59)*10(6),
      (4.17 +/- 0.40)*10(6), (9.44 +/- 1.22)*10(6) and (2.95 +/- 0.88)*10(6) copies/ug,
      the difference was significant (P < 0.05). CONCLUSION: RpoE and RpoS could
      influence the expression of lots of metabolism genes. Together, they regulated
      the metabolism and growth of S. Typhi under hyperosmotic stress.

PMID- 23866756
TI  - [Determination of volatile nitrosamines in urine through gas chromatography-mass
      spectrometry].
AB  - OBJECTIVE: To establish a detection method based on gas chromatography-mass
      spectrometry (GC-MS) for concentrations of volatile nitrosamine compounds in
      urine, and apply it to the test of real samples. METHODS: Target compounds
      dichloromethane in urine samples was extracted with dichloromethane through
      liquid-liquid extraction, then the dichloromethane extract was filtrated,
      evaporated with nitrogen at 40 degrees C to dryness, and the volume was set with
      0.2 ml dichloromethane. Analysis of nine volatile nitroso-compounds were
      performed with GC-MS under selected ion monitoring mode, external reference
      method was used for quantification, and the detection limit, repeatability and
      sensitivity were evaluated. In addition, nine volatile nitroso-compounds of 92
      urine samples in a town of Anhui province were measured. RESULTS: A good linear
      range of 2 - 200 ng/ml (with correlation coefficient 0.9985 - 0.9999) were
      obtained for the above mentioned nine kinds of analyte, and the lowest
      examination concentration was 0.05 - 0.50 ng/ml. The addition standard recoveries
      were 68%-102% with the RSD of 0.4% - 5.5% (n = 3). The detection limits were
      0.001 - 0.013 ng/ml urine. The detection rate of N-nitrosodimethylamine (NDMA), N
      nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n
      propylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N
      nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N
      nitrosodiphenylamine (NDPhA) were 71% (65), 74% (68), 65% (60), 80% (73), 92%
      (85), 78% (72), 76% (70), 87% (80), 98% (90), respectively, with the results
      (0.27 +/- 0.12), (0.75 +/- 0.29), (0.06 +/- 0.02), (0.16 +/- 0.07), (23.66 +/-
      5.18), (1.01 +/- 0.35), (0.38 +/- 0.11), (2.47 +/- 0.52) and (15.13 +/- 3.48)
      nmol/g creatinine. CONCLUSIONS: A gas chromatography-mass spectrometry detect
      method was developed for low level volatile nitrosamines in urine samples.

PMID- 23866757
TI  - [Determination of tetrodotoxin in seafood using graphitized carbon black clean-up
      with hilic ultra performance liquid chromatography-triple quadrupole mass
      spectrometry].
AB  - OBJECTIVE: To develop a rapid hilic ultra performance liquid chromatography
      (UPLC)-mass spectrum (MS)/MS method for determination of tetrodotoxin in seafood.
      METHODS: The sample of muscle and liver of puffer fish and nassarius were
      extracted with aqueous solution containing 0.2% (V/V) acetic acid (the extract of
      liver must be purified through HLB cartridge), and then cleanup of extract was
      accomplished by solid-phase extraction with a graphitized carbon black cartridge.
      The analysis of tetrodotoxin was carried out on a chromatographic column (Acquity
      UPLC BEH Amide, 100 mm*2.1 mm*1.7 um) with gradient elution of 95% (V/V)
      acetonitrile-H2O both containing 0.1% (V/V) formic acid and 2.0 mmol/L ammonium
      formate, and detected by positive electrospray ionization tandem mass
      spectrometry in the multiple reaction monitoring (MRM) mode, and quantified by
      matrix-match standard solution. RESULTS: The calibration curves were linear in
      the range of 30 - 10 000, 50 - 10 000 and 30 - 10 000 ug/kg of tetradotoxin in
      muscle and liver of puffer fish and in muscle of nassarius, respectively. The
      correlation coefficients were within 0.9963 - 0.9990. The limits of detection
      were 10, 20 and 10 ug/kg, and that of quantitation were 30, 50 and 30 ug/kg for
      muscle and liver of puffer fish and muscle of nassarius, respectively. The
      average recoveries were 81.5% - 93.1%, 82.3% - 106.0% and 83.5% - 95.2% for
      tetrodotoxin spiked in muscle and liver of puffer fish and in muscle of
      nassarius, respectively, with relative standard deviation (RSD) of 2.3% - 11%,
      4.3% - 14.0% and 3.5% - 13.0% (n = 6). CONCLUSION: The method was simple,
      accurate and sensitive, and could be successfully applied to the measurement of
      tetrodotoxin in puffer fish and nassarius.

PMID- 23866758
TI  - English-learning one- to two-year-olds do not show a consonant bias in word
      learning.
AB  - Following the proposal that consonants are more involved than vowels in coding
      the lexicon (Nespor, Pena & Mehler, 2003), an early lexical consonant bias was
      found from age 1;2 in French but an equal sensitivity to consonants and vowels
      from 1;0 to 2;0 in English. As different tasks were used in French and English,
      we sought to clarify this ambiguity by using an interactive word-learning study
      similar to that used in French, with British-English-learning toddlers aged 1;4
      and 1;11. Children were taught two CVC labels differing on either a consonant or
      vowel and tested on their pairing of a third object named with one of the
      previously taught labels, or part of them. In concert with previous research on
      British-English toddlers, our results provided no evidence of a general consonant
      bias. The language-specific mechanisms explaining the differential status for
      consonants and vowels in lexical development are discussed.

PMID- 23866759
TI  - Proteomic analysis of the inhibitory effect of epigallocatechin gallate on lipid
      accumulation in human HepG2 cells.
AB  - BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG), the most abundant catechin
      found in green tea, effectively reduces body weight and tissue and blood lipid
      accumulation. To explore the mechanism by which EGCG inhibits cellular lipid
      accumulation in free fatty acid (FFA) induced HepG2 cell culture, we investigated
      the proteome change of FFA-induced HepG2 cells exposed to EGCG using two
      dimensional gel electrophoresis and mass spectrometry. RESULTS: In this study, 36
      protein spots showed a significant change in intensity by more than 1.5-fold from
      the control group to the FFA group and from the FFA group to the FFA + EGCG
      group. Among them, 24 spots were excised from gels and identified by LC-MS/MS. In
      total, 18 proteins were successfully identified. All identified proteins were
      involved in lipid metabolism, glycometabolism, antioxidant defense, respiration,
      cytoskeleton organization, signal transduction, DNA repair, mRNA processing, iron
      storage, or were chaperone proteins. This indicated that these physiological
      processes may play roles in the mechanism of inhibition of lipid accumulation by
      EGCG in FFA-induced HepG2 cells. Western blotting analysis was used to verify the
      expression levels of differentially expressed proteins, which agree with the
      proteomic results. CONCLUSIONS: From the proteomic analysis, we hypothesized that
      EGCG reduced cellular lipid accumulation in FFA-induced HepG2 cells through the
      activation of AMP-activated protein kinase (AMPK) resulting from the generation
      of reactive oxygen species (ROS). The induction of ROS may be a result of EGCG
      regulation of the antioxidant defense system. Activation of AMPK shifted some FFA
      toward oxidation, away from lipid and triglyceride storage, and suppressed
      hepatic gluconeogenesis. The findings of this study improve our understanding of
      the molecular mechanisms of inhibition of lipid accumulation by EGCG in HepG2
      cells.

PMID- 23866760
TI  - Can informal social distancing interventions minimize demand for antiviral
      treatment during a severe pandemic?
AB  - BACKGROUND: In the case of a pandemic, individuals may alter their behaviour. A
      dynamic model incorporating social distancing can provide a mechanism to consider
      complex scenarios to support decisions regarding antiviral stockpile size while
      considering uncertainty around behavioural interventions. We have examined the
      impact of social distancing measures on the demand for limited healthcare
      resources such as antiviral drugs from a central stockpile during a severe
      pandemic. METHODS: We used an existing age-structured model for pandemic
      influenza in Canada and biologically plausible scenarios for severe influenza
      transmission within the population. We incorporated data from published reports
      regarding stated intentions to change behaviour during a pandemic as well as the
      magnitude and duration of time that individuals expected to maintain the
      behavioural change. We ran simulations for all combinations of parameter values
      to identify the projected antiviral requirements in each scenario. RESULTS: With
      12 weeks of distancing, the effect is relatively small for the lowest R0 of 1.6
      with a projected stockpile to treat 25.6% being required (IQR=21.7 - 28.7%)
      unless the proportion of people involved (81%) and magnitude of the behaviour
      change is large (69% reduction in contacts). If 24 weeks of distancing occurs,
      with only a low to moderate reduction in contacts (38% or less), it is not
      possible to bring treatment requirements below 20% regardless of what proportion
      of the population engages in distancing measures when transmissibility is high
      (R0=2.0; stockpile size=31%, IQR=29.2 - 33.5%). CONCLUSIONS: Our results
      demonstrate that the magnitude and duration of social distancing behaviours
      during a severe pandemic have an impact on the need for antiviral drugs. However,
      significant investments over a long period of time (>16 weeks) are required to
      decrease the need for antiviral treatment to below 10% of the total population
      for a highly transmissible viral strain (R0>1.8). Encouraging individuals to
      adopt behaviours that decrease their daily contact rate can help to control the
      spread of the virus until a vaccine becomes available however; relying on these
      measures to justify stockpiling fewer courses of treatment will not be sufficient
      in the case of a severe pandemic.

PMID- 23866761
TI  - Effectiveness of green tea mouthwash in postoperative pain control following
      surgical removal of impacted third molars: double blind randomized clinical
      trial.
AB  - BACKGROUND: Pain following surgical removal of impacted molars has remained an
      important concern among practitioners. Various protocols have been proposed to
      reduce postoperative pain. However, each one has special side effects and
      limitations. As green tea possesses anti-inflammatory and antibacterial
      properties, the aim of the current study was to evaluate the effectiveness of
      green tea mouthwash in controlling postoperative pain. MATERIALS AND METHODS: In
      a study with split-mouth and double blind design, 44 patients in need of
      bilateral removal of impacted third molars underwent randomized surgical
      extraction; following one surgery patients rinsed with a green tea mouthwash from
      the first to seventh postoperative day and after other extraction rinsed with
      placebo mouthwash in the same duration. Both patients and surgeon were blinded to
      the type of mouthwash. The predictor variable was type of mouthwash and primary
      outcome variable was postoperative pain measured by visual analogue scale (VAS)
      during first week after surgery. In addition, number of analgesics patients used
      after surgery recorded. To measure the effect of green tea mouthwash, repeated
      measures test with confidence interval of 95% was performed. RESULTS: Total of 43
      patients with mean age of 24 years underwent total of 86 surgeries. VAS value had
      no statistically difference prior rinsing among groups (P-value > 0.05). However,
      the mean value of VAS following rinsing with green tea was statistically lower
      than placebo in postoperative days of 3-7 (P-value < 0.05). In addition, while
      rinsing with green tea, patients took significantly lower number of analgesics
      after surgery (P-value < 0.05). No side effects reported. CONCLUSION: Green tea
      mouthwash could be an appropriate and safe choice to control postoperative pain
      after third molar surgery.

PMID- 23866762
TI  - The effect of endoscopic administration of autologous porcine muscle-derived
      cells into the urethral sphincter.
AB  - OBJECTIVE: To verify the fate of autologous porcine myogenic cells after
      endoscopic administration into the urethral sphincter. METHODS: This study was
      performed on pig animal models. The muscle-derived cells (MDCs) were isolated and
      identified. After the third passage, the 6 * 10(7) of PKH26 labeled cells were
      injected into the urethral sphincter using a urethrocystoscope. The urethras were
      collected after 28 days. To analyze the fate of injected cells, the PKH26
      presence, the desmin expression, and the distribution of acetylcholine receptors
      were evaluated in the tissue sections. Moreover, the maximal urethral closure
      pressure (MUCP) was assessed in experimental and control groups at day 1 and day
      28. RESULTS: The isolated porcine MDCs expressed desmin and were able to
      differentiate into myotubes in vitro. At day 28 after the transplantation, the
      depots of PKH26-positive cells were observed in the muscular layer, but also in
      the submucosa. The staining for desmin revealed that cells located in the muscle
      layer were integrated with muscle fibers that possessed acetylcholine receptors.
      However, cells administered into nonmuscle tissue did not express desmin.
      Urethral pressure profilometry demonstrated no significant differences between
      MUCP in the transplanted group in comparison to the control group at day 28.
      CONCLUSION: The present study demonstrates the successful endoscopic
      transplantation of myogenic cells into the urethral sphincter. The experiments
      indicated the key importance of precise cell administration in terms of their
      fate after the injection.

PMID- 23866763
TI  - Breast conserving surgery versus mastectomy: the influence of comorbidities on
      choice of surgical operation in the Department of Defense health care system.
AB  - BACKGROUND: Studies on the effect of comorbidities on breast cancer operation
      have been limited and inconsistent. This study investigated whether pre-existing
      comorbidities influenced breast cancer surgical operation in an equal access
      health care system. METHODS: This study was based on linked Department of Defense
      cancer registry and medical claims data. The study subjects were patients
      diagnosed with stage I to III breast cancer during 2001 to 2007. Logistic
      regression was used to determine if comorbidity was associated with operation
      type and time between diagnosis and operation. RESULTS: Breast cancer patients
      with comorbidities were more likely to receive mastectomy (odds ratio [OR] =
      1.27; 95% confidence interval [CI], 1.14 to 1.42) than breast conserving surgery
      plus radiation. Patients with comorbidities were also more likely to delay having
      operation than those without comorbidities (OR = 1.27; 95% CI, 1.14 to 1.41).
      CONCLUSIONS: In an equal access health care system, comorbidity was associated
      with having a mastectomy and with a delay in undergoing operation.

PMID- 23866764
TI  - Value of the pretreatment albumin to globulin ratio in predicting long-term
      mortality in breast cancer patients.
AB  - BACKGROUND: Prior studies have demonstrated the prognostic value of pretreatment
      serum albumin in different types of cancer. The aim of this study was to assess
      the predictive value of the albumin to globulin ratio (AGR) on survival in breast
      cancer patients. METHODS: This retrospective study used an unselected cohort of
      354 breast cancer patients who had documented total protein and albumin levels
      prior to chemotherapy. Survival status was obtained from our cancer registry.
      Survival analysis, stratified by AGR tertiles, was used to evaluate the
      prognostic value of AGR. RESULTS: Patients in the highest AGR tertiles (AGR >
      1.45) had a lower 5-year mortality rate compared with those in the middle (AGR
      1.21 to 1.45) and the lowest (AGR < 1.21) tertiles (6% vs. 18% and 32%, P <
      .001). After adjusting for confounding variables, AGR remained a significant
      predictor of mortality (P < .002). Moreover, after excluding the patients with
      albumin levels less than 3.6, the AGR remained a significant predictor of
      survival (P .0018). CONCLUSIONS: Pretreatment AGR is an independent, significant
      predictor of long-term mortality in breast cancer patients, even in patients with
      normal albumin levels.

PMID- 23866765
TI  - The consequence of undertreatment of patients treated with breast conserving
      therapy for ductal carcinoma in-situ.
AB  - BACKGROUND: The use of clinical features to allocate adjuvant therapy in the
      treatment of ductal carcinoma in situ with breast-conserving therapy remains
      controversial. METHODS: A review of patients with ductal carcinoma in situ
      treated with breast-conserving therapy was performed. The recurrence rate was
      examined in relation to patient age, tumor characteristics, Van Nuys Prognostic
      Index, and the receipt of prescribed adjuvant therapies. RESULTS: Six percent of
      patients (17 of 294) had developed local recurrences after a median follow-up
      period of 63 months. Fifty-nine percent of patients (91 of 154) with estrogen
      receptor-positive tumors did not receive prescribed tamoxifen. Thirty-one percent
      of patients (45 of 147) with Van Nuys Prognostic Index scores >=7 did not receive
      recommended radiation therapy. Receipt of prescribed adjuvant therapy did not
      result in a decrease in the rate of local recurrence. Patient age was the only
      factor associated with local recurrence on univariate but not on multivariate
      analysis (P = .374). CONCLUSIONS: A low rate of local recurrence was achieved
      despite a large number of patients' not receiving prescribed adjuvant therapies.

PMID- 23866766
TI  - Consumption of foods with voluntary fortification of micronutrients in southern
      Brazil: prevalence and associated factors.
AB  - OBJECTIVE: To investigate the consumption of foods with voluntary fortification
      of vitamins and minerals (FVFVM) according to demographic, socio-economic and
      health characteristics. DESIGN: A cross-sectional population-based study.
      SETTING: The investigated food groups were selected in two stages according to
      availability of food in the local market and prevalence of food consumption in a
      recent national survey. The research instruments included a questionnaire and a
      photographic catalogue. The FVFVM consumption covered a period of one week prior
      to the interview date. Statistical analyses were performed using Stata 12.0
      statistical software package, considering the design effect and a hierarchical
      model. A multinomial logistic regression was applied to estimate the prevalence
      ratios. All tests were two-tailed, with a 5.0 % significance level. SUBJECTS:
      Adults (>=20 years old) living in a southern city of Brazil. RESULTS: Between
      February and June 2012, 2925 individuals were interviewed. Losses and refusals
      corresponded to 13.4 % of the sample. The overall prevalence of FVFVM consumption
      was 73.3 (95 % CI 71.7, 75.9) %. The total number of FVFVM reported exhibited a
      distribution with a median of two and a maximum of fifteen, inflated by the FVFVM
      categorized in the 'juice' group. The micronutrients most consumed were vitamin
      C, followed by Fe and thiamin. Young adults, females, those of higher socio
      economic status and those who perceived their health positively were more likely
      to consume FVFVM. CONCLUSIONS: Prevalence of FVFVM consumption in southern
      Brazil, occurring concurrently with the decline in consumption of unprocessed and
      minimally processed foods, and the way voluntary fortification is being employed
      trigger a warning sign to primary prevention.

PMID- 23866767
TI  - AcuTrials(r): an online database of randomized controlled trials and systematic
      reviews of acupuncture.
AB  - BACKGROUND: The growing quantity of Complementary and Alternative Medicine
      literature requires databases enabled with increasingly powerful search
      capabilities. To address this need in the area of acupuncture research, a
      bibliographic database of randomized controlled trials (RCTs) and systematic
      reviews called AcuTrials(r) has been developed by the Oregon College of Oriental
      Medicine. AcuTrials(r) introduces a comprehensive keyword thesaurus that
      categorizes details of treatment protocols and research design to an extent not
      currently available in MEDLINE or other databases. DESCRIPTION: AcuTrials(r),
      which went live in January of 2010 and is updated monthly, currently contains
      over 1250 articles from more than 300 journals. Articles included are English
      language RCTs and systematic reviews that report on medical conditions in human
      subjects treated by needle acupuncture. Study details are indexed by 14 key
      domains, such as acupuncture style and needling protocol, to create an
      acupuncture-relevant, searchable keyword catalogue. Keywords follow the National
      Library of Medicine (NLM) MeSH terminology when possible, and new keywords were
      created in cases where no appropriate MeSH terms were available. The resulting
      keyword catalogue enables users to perform sensitive, targeted searches for
      particular aspects of acupuncture treatment and research design. CONCLUSIONS:
      AcuTrials(r) provides an extensive and innovative keyword catalogue of
      acupuncture research, allowing users to efficiently navigate, locate and assess
      the evidence base in ways not currently possible with other databases. By
      providing a more powerful suite of search options, the AcuTrials(r) database has
      the potential to enhance the accessibility and quality of acupuncture research.

PMID- 23866768
TI  - Learning from the implementation of inter-organisational web-based care planning
      and coordination.
AB  - In Victoria, despite strong policy support, e-care planning and coordination is
      poorly developed. The action research project discussed here was developed to
      overcome organisational and worker-level barriers to change. The project outcomes
      highlighted the need for work on the building blocks of e-care coordination that
      enhance workers' knowledge and skills, and provide permission and support for
      appropriate collaborative system and services coordination practices. 

PMID- 23866769
TI  - Genetic lineages of undifferentiated-type gastric carcinomas analysed by
      unsupervised clustering of genomic DNA microarray data.
AB  - BACKGROUND: It is suspected that early gastric carcinoma (GC) is a dormant
      variant that rarely progresses to advanced GC. We demonstrated that the dormant
      and aggressive variants of tubular adenocarcinomas (TUBs) of the stomach are
      characterized by loss of MYC and gain of TP53 and gain of MYC and/or loss of
      TP53, respectively. The aim of this study is to determine whether this is also
      the case in undifferentiated-type GCs (UGCs) of different genetic lineages: one
      with a layered structure (LS+), derived from early signet ring cell carcinomas
      (SIGs), and the other, mostly poorly differentiated adenocarcinomas, without LS
      but with a minor tubular component (TC), dedifferentiated from TUBs (LS-/TC+).
      METHODS: Using 29 surgically resected stomachs with 9 intramucosal and 20
      invasive UGCs (11 LS+ and 9 LS-/TC+), 63 genomic DNA samples of mucosal and
      invasive parts and corresponding reference DNAs were prepared from formalin
      fixed, paraffin-embedded tissues with laser microdissection, and were subjected
      to array-based comparative genomic hybridization (aCGH), using 60K microarrays,
      and subsequent unsupervised, hierarchical clustering. Of 979 cancer-related genes
      assessed, we selected genes with mean copy numbers significantly different
      between the two major clusters. RESULTS: Based on similarity in genomic copy
      number profile, the 63 samples were classified into two major clusters. Clusters
      A and B, which were rich in LS+ UGC and LS-/TC+ UGC, respectively, were
      discriminated on the basis of 40 genes. The aggressive pattern was more
      frequently detected in LS-/TC+ UGCs, (20/26; 77%), than in LS+UGCs (17/37; 46%; P
      = 0.0195), whereas no dormant pattern was detected in any of the UGC samples.
      CONCLUSIONS: In contrast to TUBs, copy number alterations of MYC and TP53
      exhibited an aggressive pattern in LS+ SIG at early and advanced stages,
      indicating that early LS+ UGCs inevitably progress to an advanced GC. Cluster B
      (enriched in LS-/TC+) exhibited more frequent gain of driver genes and a more
      frequent aggressive pattern than cluster A, suggesting potentially worse
      prognosis in UGCs of cluster B.

PMID- 23866770
TI  - Absenteeism amongst health workers--developing a typology to support empiric work
      in low-income countries and characterizing reported associations.
AB  - The contribution of inadequate health worker numbers and emigration have been
      highlighted in the international literature, but relatively little attention has
      been paid to absenteeism as a factor that undermines health-care delivery in low
      income countries. We therefore aimed to review the literature on absenteeism from
      a health system manager's perspective to inform needed work on this topic.
      Specifically, we aimed to develop a typology of definitions that might be useful
      to classify different forms of absenteeism and identify factors associated with
      absenteeism. Sixty-nine studies were reviewed, only four were from sub-Saharan
      Africa where the human resources for health crisis is most acute. Forms of
      absenteeism studied and methods used vary widely. No previous attempt to develop
      an overarching approach to classifying forms of absenteeism was identified. A
      typology based on key characteristics is proposed to fill this gap and considers
      absenteeism as defined by two key attributes, whether it is: planned/unplanned,
      and voluntary/involuntary. Factors reported to influence rates of absenteeism may
      be broadly classified into three thematic categories: workplace and content,
      personal and organizational and cultural factors. The literature presents an
      inconsistent picture of the effects of specific factors within these themes
      perhaps related to true contextual differences or inconsistent definitions of
      absenteeism.

PMID- 23866771
TI  - Psychological advocacy toward healing (PATH): study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Domestic violence and abuse (DVA), defined as threatening behavior or
      abuse by adults who are intimate partners or family members, is a key public
      health and clinical priority. The prevalence of DVA in the United Kingdom and
      worldwide is high, and its impact on physical and mental health is detrimental
      and persistent. There is currently little support within healthcare settings for
      women experiencing DVA. Psychological problems in particular may be difficult to
      manage outside specialist services, as conventional forms of therapy such as
      counseling that do not address the violence may be ineffective or even harmful.
      The aim of this study is to assess the overall effectiveness and cost
      effectiveness of a novel psychological intervention tailored specifically for
      survivors of DVA and delivered by domestic violence advocates based in third
      sector organizations. METHODS AND STUDY DESIGN: This study is an open, pragmatic,
      parallel group, individually randomized controlled trial. Women ages 16 years and
      older experiencing domestic violence are being enrolled and randomly allocated to
      receive usual DVA agency advocacy support (control) or usual DVA agency support
      plus psychological intervention (intervention). Those in the intervention group
      will receive eight specialist psychological advocacy (SPA) sessions weekly or
      fortnightly, with two follow-up sessions, 1 month and then 3 months later. This
      will be in addition to any advocacy support sessions each woman receives. Women
      in the control group will receive usual DVA agency support but no additional SPA
      sessions. The aim is to recruit 250 women to reach the target sample size. The
      primary outcomes are psychological well-being and depression severity at 1 yr
      from baseline, as measured by the Clinical Outcomes in Routine Evaluation-Outcome
      Measure (CORE-OM) and the Patient Health Questionnaire (PHQ-9), respectively.
      Secondary outcome measures include anxiety, posttraumatic stress, severity and
      frequency of abuse, quality of life and cost-effectiveness of the intervention.
      Data from a subsample of women in both groups will contribute to a nested
      qualitative study with repeat interviews during the year of follow-up.
      DISCUSSION: This study will contribute to the evidence base for management of the
      psychological needs of women experiencing DVA. The findings will have important
      implications for healthcare commissioners and providers, as well as third sector
      specialist DVA agencies providing services to this client group. TRIAL
      REGISTRATION: ISRCTN58561170.

PMID- 23866772
TI  - Community-onset Staphylococcus aureus infections presenting to general practices
      in South-eastern Australia.
AB  - Community-acquired Staphylococcus aureus infections are a public health concern,
      yet little is known about infections that do not present to hospital. We
      identified community-onset S. aureus infections via specimens submitted to a
      community-based pathology service. Referring doctors confirmed eligibility and
      described infection site, severity and treatment. Isolates were characterized on
      antibiotic resistance, PFGE, MLST/SCCmec, and Panton-Valentine leukocidin (PVL),
      representing 106 community-onset infections; 34 non-multiresistant methicillin
      resistant S. aureus (nmMRSA) (resistant to <3 non-beta-lactam antibiotics), 15
      multiply antibiotic-resistant MRSA (mMRSA) and 57 methicillin-sensitive S. aureus
      (MSSA). Most (93%) were skin and soft tissue infections. PVL genes were carried
      by 42% of nmMRSA isolates [95% confidence interval (CI) 26-61] and 15% of MSSA
      (95% CI 8-28). PVL was associated with infections of the trunk, head or neck
      (56.4% vs. 24.3%, P=0.005) in younger patients (23 vs. 52 years, P<0.001), and
      with boils or abscesses (OR 8.67, 95% CI 2.9-26.2), suggesting underlying
      differences in exposure and/or pathogenesis.

PMID- 23866773
TI  - The Lyme disease spirochete Borrelia burgdorferi induces inflammation and
      apoptosis in cells from dorsal root ganglia.
AB  - BACKGROUND: Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia
      burgdorferi, affects both the peripheral and the central nervous systems.
      Radiculitis or nerve root inflammation, which can cause pain, sensory loss, and
      weakness, is the most common manifestation of peripheral LNB in humans. We
      previously reported that rhesus monkeys infected with B. burgdorferi develop
      radiculitis as well as inflammation in the dorsal root ganglia (DRG), with
      elevated levels of neuronal and satellite glial cell apoptosis in the DRG. We
      hypothesized that B. burgdorferi induces inflammatory mediators in glial and
      neuronal cells and that this inflammatory milieu precipitates glial and neuronal
      apoptosis. METHODS: To model peripheral neuropathy in LNB we incubated normal
      rhesus DRG tissue explants with live B. burgdorferi ex vivo and identified immune
      mediators, producer cells, and verified the presence of B. burgdorferi in tissue
      sections by immunofluorescence staining and confocal microscopy. We also set up
      primary cultures of DRG cells from normal adult rhesus macaques and incubated the
      cultures with live B. burgdorferi. Culture supernatants were subjected to
      multiplex ELISA to detect immune mediators, while the cells were evaluated for
      apoptosis by the in situ TUNEL assay. A role for inflammation in mediating
      apoptosis was assessed by evaluating the above phenomena in the presence and
      absence of various concentrations of the anti-inflammatory drug dexamethasone. As
      Schwann cells ensheath the dorsal roots of the DRG, we evaluated the potential of
      live B. burgdorferi to induce inflammatory mediators in human Schwann cell (HSC)
      cultures. RESULTS: Rhesus DRG tissue explants exposed to live B. burgdorferi
      showed localization of CCL2 and IL-6 in sensory neurons, satellite glial cells
      and Schwann cells while IL-8 was seen in satellite glial cells and Schwann cells.
      Live B. burgdorferi induced elevated levels of IL-6, IL-8 and CCL2 in HSC and DRG
      cultures and apoptosis of sensory neurons. Dexamethasone reduced the levels of
      immune mediators and neuronal apoptosis in a dose dependent manner. CONCLUSION:
      In this model, B. burgdorferi induced an inflammatory response and neuronal
      apoptosis of DRG. These pathophysiological processes could contribute to
      peripheral neuropathy in LNB.

PMID- 23866774
TI  - Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose
      combinations for the treatment of uncomplicated Plasmodium falciparum malaria
      among children aged six to 59 months in Nimba County, Liberia: an open-label
      randomized non-inferiority trial.
AB  - BACKGROUND: Prospective efficacy monitoring of anti-malarial treatments is
      imperative for timely detection of resistance development. The in vivo efficacy
      of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to
      that of artemether-lumefantrine (AL) among children aged six to 59 months in
      Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and
      efficacy data are scarce. METHODS: An open-label, randomized controlled non
      inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC
      (ASAQ Winthrop(r)) to AL (Coartem(r)) in 300 children aged six to 59 months with
      uncomplicated falciparum malaria. Inclusion was between December 2008 and May
      2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a
      day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and
      lumefantrine blood-concentrations were also measured. RESULTS: The day 42
      genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ
      and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in
      day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were
      confirmed by observed proportion of patients cured at day 42 on the per-protocol
      population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The
      probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ)
      and 0.66 [0.57-0.73] (AL) (p = 0.017). CONCLUSIONS: Both ASAQ and AL were highly
      efficacious and ASAQ was non-inferior to AL. The proportion of patients with re
      infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC
      was adopted as the first-line national treatment in Liberia. Continuous efficacy
      monitoring is recommended. TRIAL REGISTRATION: The protocols were registered with
      Current Controlled Trials, under the identifier numbers ISRCTN51688713,
      ISRCTN40020296.

PMID- 23866775
TI  - A qPCR-based metric of Th2 airway inflammation in asthma.
AB  - BACKGROUND: Using microarray profiling of airway epithelial cells, we previously
      identified a Th2-high molecular phenotype of asthma based on expression of
      periostin, CLCA1 and serpinB2 and characterized by specific inflammatory,
      remodeling, and treatment response features. The goal of the current study was to
      develop a qPCR-based assay of Th2 inflammation to overcome the limitations of
      microarray-based methods. METHODS: Airway epithelial brushings were obtained by
      bronchoscopy from two clinical studies comprising 44 healthy controls and 62
      subjects with asthma, 39 of whom were studied before and after a standardized 8
      week course of inhaled corticosteroids (ICS). The qPCR-based expression of
      periostin, CLCA1 and serpinB2 were combined into a single metric. RESULTS: In
      asthma, the three-gene-mean of periostin, CLCA1 and serpinB2 correlated with FeNO
      (r = 0.75, p = 0.0002), blood eosinophils (r = 0.58, p = 0.003) and PC20
      methacholine (r = -0.65, p = 0.0006), but not total serum IgE (r = 0.33, p =
      0.1). Higher baseline three-gene-mean correlated with greater improvement in FEV1
      with ICS at 2, 4 and 8 weeks (all p < 0.05). By ROC analysis, the area under the
      curve (AUC) of the three-gene-mean for FEV1 improvement with ICS at 4 and 8 weeks
      was 0.94 and 0.87, respectively, which are higher than the AUCs of FeNO, blood
      eosinophils, IgE or PC20. Th2 airway inflammation as measured by this three-gene
      mean also had predictive capacity for an improvement in symptoms. CONCLUSIONS:
      The three-gene-mean of periostin, CLCA1 and serpinB2 in airway epithelial
      brushings identifies Th2-high and low populations, is correlated with other Th2
      biomarkers, and performs well for prediction of FEV1 improvement with ICS. The
      three-gene-mean provides a measurement of Th2 airway inflammation that is
      clinically relevant and that can serve as a valuable tool to evaluate non
      invasive biomarkers to predict treatment responses to existing and emerging
      asthma therapies.

PMID- 23866776
TI  - Sinonasal bony changes in nasal polyposis: prevalence and relationship to disease
      severity.
AB  - BACKGROUND: Nasal polyposis is characterised by opacification of the nasal
      cavities, paranasal sinuses and ostiomeatal complexes on computed tomography
      scanning. Sinonasal bony changes have been reported as disease sequelae.
      OBJECTIVES: To assess the prevalence of sinonasal bone expansion, erosion and
      thickening in patients with nasal polyposis, and to correlate disease severity
      with the prevalence of bony changes. METHODS: A retrospective radiological study
      was conducted comprising pre-operative computed tomography scans of 104 patients
      with nasal polyposis and scans of 44 age- and gender-matched individuals (control
      group) without sinonasal disease. Lund-Mackay scores and bony changes were
      quantified. RESULTS: Ninety-three per cent of the study group scans showed
      sinonasal bony change, with no changes in the control group. Radiological
      severity of nasal polyposis correlated positively with the prevalence of bony
      changes (rs = 0.31; p < 0.01). CONCLUSION: Sinonasal bony changes were common in
      the study group. This highlights the importance of pre- and intra-operative
      imaging, which can help to prevent intra-operative complications. As bony changes
      may mimic invasive disease, the importance of histological assessment of polyps
      is emphasised.

PMID- 23866777
TI  - Potential biomarkers for predicting outcomes in CABG cardiothoracic surgeries.
AB  - The variations in recovery time, complications, and survival among cardiac
      patients who have undergone coronary artery bypass graft (CABG) procedures are
      vast. Many formulas and theories are used to predict clinical outcome and
      recovery time, and current prognostic predictions are based on medical and family
      history, lifestyle, co-morbidities, and performance status. The identification of
      biomarkers that provide concrete evidence supporting clinical outcome has greatly
      affected the field of medicine, helping clinicians in many medicine sub
      specialties to forecast clinical course. Recent studies have discovered
      biomarkers that may be used as predictors of cardiac patients' status post
      cardiothoracic surgery, and the applications are numerous. In this review, we
      assess currently available cardiac biomarkers as predictors of clinical outcome
      for post-operative CABG patients. Data were collected from various studies in
      which cardiac biomarkers were measured in pre-operative and post-operative CABG
      patients. 

PMID- 23866778
TI  - Mandibular reconstruction using intraoral microvascular anastomosis following
      removal of an ameloblastoma.
AB  - Ameloblastoma is a histologically benign, locally aggressive tumor arising from
      the odontogenic ectoderm. It accounts for 1% of all oral tumors and for 9% to 11%
      of all odontogenic tumors. In up to 96.6%, the tumor can be found in the
      mandible, predominantly in the molar region. High recurrence rates of up to 90%
      have been described with conservative treatment. Recurrences most often occur
      after 2 to 5 years. After radical resection, significantly lower recurrence rates
      have been reported, sometimes as low as 3.6%. As a consequence, when recurrence
      rate is the main concern, there is a tendency to prefer radical resection of the
      ameloblastoma. Microvascular segmental reconstruction of the mandible that uses
      an intraoral anastomosis technique has not been described in the current
      literature. Therefore, the present study aimed at extending the armamentarium of
      bony microvascular reconstruction in cases of segmental mandibulectomy by
      describing an intraoral microvascular anastomosing technique. 

PMID- 23866779
TI  - Comparative radiologic analyses of newly formed bone after maxillary sinus
      augmentation with and without bone grafting.
AB  - PURPOSE: The present study examined the formation and density of new bone after
      sinus membrane elevation, with and without bone grafting, and evaluated the bone
      formation at the apices of the implants with these 2 different maxillary sinus
      floor elevation techniques. MATERIALS AND METHODS: In a prospective randomized
      controlled study design, patients requiring reconstruction of their atrophic
      maxilla were included and divided randomly into grafted and nongrafted groups.
      Implants were inserted in each group by way of sinus membrane elevation. The
      formation and density of new bone were evaluated using cone beam computed
      tomography, performed preoperatively and 1 week, 3 weeks, and 6 months
      postoperatively. RESULTS: A total of 24 implants were placed in 14 patients, with
      all implants maintaining stability during 6 months of follow-up. New bone
      formation was determined in both groups using radiography. No significant
      differences were found between the 2 groups in terms of new bone density
      preoperatively nor at 1 week or 3 months postoperatively. However, the density of
      bone in the nongrafted group was higher than that in the grafted group 6 months
      after surgery. CONCLUSIONS: These results suggest that the simple elevation of
      the sinus membrane without bone grafting material can lead to bone formation
      around implants and that the newly formed bone in the nongrafted group was denser
      than that in the grafted group.

PMID- 23866780
TI  - Efficiency of bupivacaine versus lidocaine and methylprednisolone versus placebo
      to reduce postoperative pain and swelling after surgical removal of mandibular
      third molars: a randomized, double-blinded, crossover clinical trial.
AB  - PURPOSE: To compare 4 treatment combinations to reduce postoperative pain and
      swelling after surgical removal of mandibular third molars. PATIENTS AND METHODS:
      Patients scheduled for bilateral mandibular third molar removal were randomized
      to 1 of 4 treatment groups in a double-blinded crossover design: 1) first
      operation: lidocaine and placebo, second operation: bupivacaine and
      methylprednisolone; 2) first operation: bupivacaine and methylprednisolone,
      second operation: lidocaine and placebo; 3) first operation: lidocaine and
      methylprednisolone, second operation: bupivacaine and placebo; 4) first
      operation: bupivacaine and placebo, second operation: lidocaine and
      methylprednisolone. Patient-reported pain and swelling were recorded using visual
      analog scales 2, 4, 6, 8, and 12 hours after surgery and daily during the first
      postoperative week. The treatment effects were estimated as contrasts between the
      average differences within the treatment groups and assessed by stratified t
      tests. RESULTS: A total of 126 patients (57 women and 69 men; mean age, 25.0
      years) were included in the analysis. No significant interactions between local
      analgesia and methylprednisolone were observed. The administration of bupivacaine
      resulted in less postoperative pain up to 12 hours after surgery (P < .004) and
      more postoperative swelling 4 to 12 hours after surgery (P < .001) compared with
      lidocaine. The administration of methylprednisolone resulted in less
      postoperative pain 4 to 12 hours and 2 days after surgery (P < .05) and less
      postoperative swelling 6 and 12 hours and 1 to 3 days after surgery (P < .04)
      compared with placebo. CONCLUSIONS: Bupivacaine combined with methylprednisolone
      reduced the postoperative pain and swelling compared with the use of lidocaine
      and placebo, lidocaine and methylprednisolone, or bupivacaine and placebo.

PMID- 23866781
TI  - A preliminary study on the application of bone marrow stromal cell sheet on the
      formation of functional tissue-engineered bone in dogs.
AB  - PURPOSE: The aim of this study was to construct functional tissue-engineered bone
      in dogs using cell sheet engineering, a new technique to gain and transfer seed
      cells. MATERIALS AND METHODS: Demineralized bone matrixes, prepared from
      homologous bone, were coated with recombinant human bone morphogenetic protein-2.
      Bone marrow stromal cells (BMSCs) were isolated and subcultured. Osteogenic
      induced BMSCs were incubated in a temperature-responsive culture dish to form the
      BMSC sheet. The complex of demineralized bone matrix, recombinant human bone
      morphogenetic protein-2, and BMSCs wrapped with BMSC sheets was implanted around
      the blood vessels of the latissimus dorsi muscle in the experimental side, and
      the same complex without BMSC sheets was implanted around the blood vessels of
      the latissimus dorsi muscle on the other side as a control. At 4, 8, 12, and 16
      weeks after implantation, the implants were removed for radiographic evaluation,
      descriptive histologic observation, and histologic quantitative analysis.
      RESULTS: Radiographic analysis showed that the optical density of the tissue
      engineered bone on the 2 sides increased with time. However, the optical density
      of the experimental side was significantly greater than that of the control side
      at the same points. Sixteen weeks after implantation, mature lamellar bone was
      formed in the experimental side, with red bone marrow in the bone marrow cavity.
      In contrast, the control side exhibited significantly less lamellar bone.
      Histologic quantitative analysis showed that the experimental side exhibited
      significantly more bone per area compared with the control side. CONCLUSION: BMSC
      sheet engineering may be useful to construct functional tissue-engineered bone.

PMID- 23866782
TI  - Effect of menstrual cycle on frequency of alveolar osteitis in women undergoing
      surgical removal of mandibular third molar: a single-blind randomized clinical
      trial.
AB  - PURPOSE: To measure the association between the menstrual cycle and the frequency
      of alveolar osteitis (AO). MATERIALS AND METHODS: In a study with a single-blind
      design, patients with bilateral impacted third molar teeth underwent randomized
      surgical extraction: one tooth during the menstrual period and one during the
      middle of the cycle. The postoperative examiner was unaware of the menstrual
      cycle status of the patients. The predictor variable was the timing of the
      menstrual cycle and was grouped as mid-cycle and menstrual period. The outcome
      variable was AO, which was measured (without knowledge of the menstrual cycle
      timing) at 2 to 7 days postoperatively. Other study variables included oral
      contraceptive (OC) use, smoking status, irrigation used during surgery,
      extraction difficulty, surgeon experience, number of local anesthetic cartridges
      used, and patient age. Appropriate bi- and multivariate statistics were computed,
      and the level of statistical significance was set at P < .05. RESULTS: A total of
      145 female patients, with a mean age of 24 years, underwent 290 third molar
      extractions. The overall frequency of AO was 23.45%. The frequency of AO was
      significantly greater in the middle of the cycle than during the menstrual period
      inboth the OC users and nonusers (P < .05). Although OC users revealed a
      significantly greater frequency of AO compared with nonusers (P < .05), no
      statistically significant differences were found between the 2 groups during the
      menstrual period (P > .05). CONCLUSIONS: According to the results of the present
      study, the menstrual cycle could be a determinant risk factor in the frequency of
      AO. We recommend that elective procedures be performed during the menstrual
      period in both OC users and nonusers to eliminate the effect of cycle-related
      hormonal changes on the development of AO.

PMID- 23866783
TI  - Le Fort II fractures are associated with death: a comparison of simple and
      complex midface fractures.
AB  - PURPOSE: To investigate whether complex midface fractures have a greater
      association with death and intracranial injury than simple midface fractures.
      MATERIALS AND METHODS: A retrospective chart review was performed for patients
      with blunt-mechanism midface fractures who had presented to an urban trauma
      center from 1998 to 2010. The survival and intracranial injury status was
      evaluated for patients with simple and complex midface fractures, including Le
      Fort, naso-orbitoethmoid, and/or zygomaticomaxillary fractures. Intracranial
      injury included hemorrhage and brainstem injury. Patients with upper face
      fractures were excluded to minimize confounding. Adjusted relative risk estimates
      were obtained using multivariate regression analysis. RESULTS: Of 3,291 patients
      with midface fractures, 213 (6.3%) died and 693 (21.3%) had an intracranial
      injury. The cumulative mortality reached 11.6% in patients with complex midface
      fractures and 5.1% in those with simple midface fractures (P < .001). Patients
      with complex midface fractures were 57% more likely to die (relative risk = 1.57;
      P < .005). Specifically, Le Fort II fractures independently conferred a 94%
      increased risk of death (relative risk = 1.94; P < .01), but Le Fort I and III
      fractures were not significantly associated with death. Among patients presenting
      without neurologic impairment, those with Le Fort II and III fractures remained
      2.88-fold (P < .01) and 2.54-fold (P < .001) more likely to have an underlying
      intracranial injury, respectively. CONCLUSIONS: Le Fort II fractures are
      associated with increased mortality. Furthermore, Le Fort II and III fractures
      are associated with serious intracranial injury, even in the absence of
      alterations in consciousness. These patients should be monitored with heightened
      vigilance and followed up closely during hospitalization, regardless of the
      presenting clinical findings.

PMID- 23866784
TI  - High prevalence of diagnosis of diabetes, depression, anxiety, hypertension,
      asthma and COPD in the total population of Stockholm, Sweden - a challenge for
      public health.
AB  - BACKGROUND: There is limited knowledge on the prevalence of disease in total
      populations. Such studies have historically been difficult to conduct but the
      development of health data registers has facilitated large-scale studies on
      recorded diagnoses in entire regions. The aim of this study was to analyze the
      prevalence of diagnosis of six common diseases in the Swedish capital region.
      METHODS: The study population included all living persons who resided in
      Stockholm County, Sweden, on December 31st 2011 (N=2 093 717). Information on all
      consultations between 2007 and 2011 was obtained from primary health care,
      specialist outpatient care and inpatient care. Prevalence was defined as the
      proportion of individuals with a recorded diagnosis of diabetes, depression,
      anxiety disorders, hypertension, asthma and chronic obstructive pulmonary disease
      during the five year period, respectively. Analyses were done by age and gender.
      RESULTS: Hypertension had the highest five-year prevalence (12.2%), followed by
      depression (6.6%), diabetes mellitus (6.2%), asthma (5.9%), anxiety
      disorders/phobia (4.8%), and COPD (1.8%). Diabetes was more common in men (5.3%
      of women and 7.1% of men) while depression (8.7% in women and 4.4% in men) and
      anxiety (6.3% in women and 3.4% in men) were considerably more common in women.
      Smaller gender differences were also found for hypertension (13.0% in women and
      11.4% in men), asthma (6.4% in women and 5.4% in men) and COPD (2.1% in women and
      1.6% in men). Diabetes, hypertension and COPD increased markedly with age,
      whereas anxiety, depression and asthma were fairly constant in individuals above
      18 years. During one year of observation, more than half of all patients had only
      been diagnosed in primary health care, with hypertension being the diagnosis with
      the largest proportion of patients only identified in primary health care
      (70.6%). CONCLUSION: The prevalence of common diseases in the population can be
      estimated by combining data gathered during consecutive years from primary care,
      specialist outpatient care and inpatient care. However, accuracy of disease
      prevalence is highly dependent on the quality of the data. The high prevalence of
      the six diagnoses analysed in this study calls for preventive action to minimize
      suffering and costs to society.

PMID- 23866785
TI  - A new type of protein chip to detect hepatocellular carcinoma-related autoimmune
      antibodies in the sera of hepatitis C virus-positive patients.
AB  - BACKGROUND: We report here a new type of protein chip to detect antibodies in
      sera. This chip method was used to a prototype created to detect hepatocellular
      carcinoma (HCC) -related autoantibodies in the sera of hepatitis C virus (HCV)
      infected individuals. RESULTS: Five cysteine-tagged (Cys-tag) and green
      fluorescent protein (GFP)-fused recombinant heat shock protein 70 (HSP70),
      superoxide dismutase 2 (SOD2), and peroxiredoxin 6 (PRDX6), were spotted and
      immobilized on maleimide-incorporated diamond-like carbon (DLC) substrates. The
      antibodies in diluted sera were trapped by these proteins at each spot on the
      chip, and visualized by a fluorescence-conjugated anti-human IgG. The total
      immobilized protein level of each spot was detected with anti-GFP mouse IgG and a
      fluorescence-conjugated secondary anti-mouse IgG. The ratio between the two
      fluorescence intensities was used to quantify autoantibody levels in each serum
      sample. Heat treatment of the chip in a solution of denaturing and reducing
      agents, before serum-incubation, improved autoantibody detection. We tested serum
      samples from healthy individuals and HCC patients using the chips. The HSP70
      autoantibodies were found at high levels in sera from HCV-positive HCC patients,
      but not in HCV-negative sera. CONCLUSION: This protein chip system may have
      useful properties to capture a specific set of antibodies for predicting the
      onset of particular cancers such as HCC in HCV-infected individuals.

PMID- 23866786
TI  - The impact of atherosclerosis and vascular collagen on energy-based vessel
      sealing.
AB  - BACKGROUND: Bipolar energy ligation of vessels in surgery is common. Although
      rare, serious failures occur. Atherosclerosis may contribute to seal failures by
      altering vascular compressibility and collagen content; however, no data exist.
      MATERIALS AND METHODS: Femoral and iliac arteries of six Yucatan swine with an
      identified genetic locus predisposing them to atherosclerosis were denuded with a
      Fogarty catheter. Animals were fed a high-fat diet for 28 wk. A Yorkshire pig was
      used as a normal control and fed a standard diet. At 28 wk, arteries were
      measured for their diameters, sealed, and divided in vivo with LigaSure. The
      sealed artery sections were excised and subjected to burst pressure testing. Half
      of the seal distal to the aorta was kept intact for histology and collagen and
      elastin quantification. A multiple linear regression model was used to assess
      variables contributing to burst pressure. Covariates included were vessel
      diameter, degree of atherosclerosis, and collagen content. RESULTS: Experimental
      animals were hypercholesterolemic. Atherosclerosis occurred in 90% of seals in
      induced animals, with severe atherosclerosis in 62% of seals. There was site
      selective deposition of atherosclerotic plaques in larger diameter iliac vessels.
      A model including collagen and size best predicted burst pressure. Every 10-U
      increase in collagen resulted in 15% increase in burst pressure (95% confidence
      interval = 0.2%-32%, P = 0.047, R(2) = 0.36). Atherosclerosis was unrelated to
      burst pressure controlling for collagen and size. CONCLUSIONS: Collagen and size
      provide the best model fit for predicting burst pressure. Quantitative research
      in human vasculature is warranted to better understand the influence of
      atherosclerosis and collagen content on seal failures.

PMID- 23866787
TI  - Intraperitoneal drainage after pancreatic resection: a review of the evidence.
AB  - BACKGROUND: Despite a growing body of literature supporting the limited use of
      prophylactic intra-abdominal drainage for many procedures, drain placement after
      pancreatic resection remains commonplace and highly controversial. MATERIALS AND
      METHODS: Literature available in the PubMed was systematically reviewed by
      searching using combinations of keywords and citations in review articles
      regarding prophylactic drainage after pancreatic resection, early removal of
      intraoperatively placed drains after pancreatic resections, and risk factors and
      predictive tools for pancreatic fistula. RESULTS: Prospective randomized studies
      on prophylactic drainage after pancreaticoduodenectomy or distal pancreatectomy
      have not shown any benefit in decreasing pancreatic fistula, total complications,
      length of hospital stay, or readmission rates. Frequency of complications was
      significantly higher in patients receiving routine drainage. This was recently
      supported by retrospective studies; however, patients with risk factors for
      pancreatic fistula (soft pancreatic texture, prolonged operative times, and
      increased blood loss) were more likely to have prophylactic intra-abdominal
      drainage. Alternatively, if a drain is placed, prospective randomized studies
      demonstrate that early removal is safe in patients with postoperative day 1 drain
      amylase values <5000 U/L and associated with a lower rate of fistula.
      CONCLUSIONS: The current literature supports a strategy of selective drainage and
      early drain removal after pancreatic resection in low-risk patients.

PMID- 23866788
TI  - Sensitivity of endoscopic retrograde cholangiopancreatography standard cytology:
      10-y review of the literature.
AB  - BACKGROUND: Biliary strictures present a unique diagnostic challenge to
      clinicians as they can be caused by both benign and malignant conditions. With
      the high mortalities associated with hepatopancreaticobiliary malignancies,
      accurate and rapid tissue diagnosis is imperative and typically done before
      initiation of treatment. However, the exact sensitivity of standard cytology from
      endoscopic retrograde cholangiopancreatography (ERCP) to diagnose malignancy
      remains unclear because of wide distribution of reported values in the
      literature. Furthermore, the use of radical surgery to obtain tissue when
      cytology is indeterminate has led to questions about the role of ERCP in patients
      with biliary strictures. METHODS: A PubMed search was conducted using the terms
      ERCP, cytology, and brushings. Articles reviewed were published between 2002 and
      2012, had patient population with biliary stricture, and had ERCP brushing
      results and final pathology available for review. The cytology and pathology data
      were abstracted from each study, and the combined overall sensitivity was
      calculated. RESULTS: Sixteen studies were identified, with sensitivities ranging
      from 6%-64% and 99% confidence intervals (CIs) ranging from +/-6% to +/-32%. A
      combined total of 1556 patients were included, with positive ERCP cytology
      results in 358 cases. On final pathology, however, 861 patients were positive for
      malignancy. When the data were combined, we found an overall sensitivity of 41.6%
      +/- 3.2% (99% CI) with a negative predictive value of 58.0% +/- 3.2% (99% CI).
      CONCLUSIONS: ERCP brushings suffer from low sensitivity and negative predictive
      value. This study questions the utility of ERCP to change the surgical management
      of these diseases in patients with radiographic evidence of a neoplasm or high
      suspicion of a malignancy.

PMID- 23866789
TI  - Fenofibrate does not affect burn-induced hepatic endoplasmic reticulum stress.
AB  - BACKGROUND: Burn injury causes major metabolic derangements such as
      hypermetabolism, hyperlipidemia, and insulin resistance and is associated with
      liver damage, hepatomegaly, and hepatic endoplasmic reticulum (ER) stress.
      Although the physiological consequences of such derangements have been
      delineated, the underlying molecular mechanisms remain unknown. Previously, it
      was shown that fenofibrate improves patient outcome by attenuating postburn
      stress responses. METHODS: Fenofibrate, a peroxisome proliferator-activated
      receptor alpha agonist, regulates liver lipid metabolism and has been used to
      treat hypertriglyceridemia and hypercholesterolemia for many years. The aim of
      the present study is to determine the effects of fenofibrate on burn-induced
      hepatic morphologic and metabolic changes. We randomized rats to sham, burn
      injury, and burn injury plus fenofibrate. Animals were sacrificed and livers were
      assessed at 24 or 48 h post burn. RESULTS: Burn injury decreased albumin and
      increased alanine transaminase (P = 0.1 versus sham), indicating liver injury.
      Fenofibrate administration did not restore albumin or decrease alanine
      transaminase. In addition, ER stress was significantly increased after burn
      injury both with and without fenofibrate (P < 0.05 versus sham). Burn injury
      increased fatty acid metabolism gene expression (P < 0.05 versus sham),
      downstream of peroxisome proliferator-activated receptor alpha. Fenofibrate
      treatment increased fatty acid metabolism further, which reduced postburn hepatic
      steatosis (burn versus sham P < 0.05, burn + fenofibrate versus sham not
      significant). CONCLUSIONS: Fenofibrate did not alleviate thermal injury-induced
      hepatic ER stress and dysfunction, but it reduced hepatic steatosis by modulating
      hepatic genes related to fat metabolism.

PMID- 23866790
TI  - Endogenous HMGB1 is required in endotoxin tolerance.
AB  - BACKGROUND: High-mobility group box 1 protein (HMGB1), a downstream inflammatory
      response modifier in sepsis and endotoxemia, alters endotoxin tolerance by
      affecting cellular hyporesponsiveness and tumor necrosis factor alpha and
      interleukin 1 production. OBJECTIVE: Endogenous HMGB1 signaling mechanisms during
      low-dose lipopolysaccharide (LPS)-induced endotoxin tolerance were investigated.
      METHODS: BALB/c mice were preconditioned with either 0.1 mL low-dose LPS (0.2
      mg/kg) or phosphate-buffered saline (PBS) (control) followed by treatment with
      three consecutive injections of anti-HMGB1, IgY (an nonspecific antibody), or
      PBS, at 2, 12, and 22 h, respectively, Mice were then subjected to 0.1 mL high
      dose LPS (10 mg/kg) or PBS at 24 h. Serum and hepatic tissue samples were
      obtained 1 or 3 h after final treatments. Signaling mechanisms were further
      investigated in the serum and hepatic tissues of mice preconditioned with 0.1 mL
      HMGB1 (1 mg/kg), low-dose LPS (0.2 mg/kg), or PBS for 1 h, and then high-dose LPS
      treatment for 3 h. RESULTS: The signaling mechanisms involved in low-dose LPS
      preconditioning required enhanced endogenous HMGB1 expression and secretion.
      Neutralizing endogenous HMGB1 with anti-HMGB1 antibodies following low-dose LPS
      preconditioning altered endotoxin tolerance by increasing serum tumor necrosis
      factor alpha, reducing hepatic interleukin-1R-associated kinase M expression, and
      partially restoring nuclear factor kappaB in vivo. The translocation from nucleus
      to cytoplasm of endogenous HMGB1 in RAW264.7 cells was also observed during low
      dose LPS-induced endotoxin tolerance. CONCLUSIONS: Increased interleukin-1R
      associated kinase M and decreased nuclear factor kappaB activity in endotoxin
      tolerance is associated with endogenous HMGB1 expression after low-dose LPS
      preconditioning. These findings provide a basis for a better mechanistic
      understanding and the development of safer clinical therapeutics utilizing
      induced endotoxin tolerance.

PMID- 23866791
TI  - Non-invasive monitoring of core body temperature rhythms over 72 h in 10
      bedridden elderly patients with disorders of consciousness in a Japanese
      hospital: a pilot study.
AB  - The purpose of this study was to elucidate the body core temperature rhythms of
      bedridden elderly patients with disorders of consciousness (DOC) in a Japanese
      hospital using a simple, non-invasive, deep-body thermometer. We measured body
      core temperature on the surface of abdomen in 10 bedridden elderly patients with
      DOC continuously over 72 h. A non-heated core body temperature thermometer was
      used. The cycle of the body core temperature rhythm was initially derived by
      using the least squares method. Then, based on that rhythm, the mean, amplitude,
      and times of day of the highest and lowest body temperatures during the optimum
      cycle were determined using the cosinor method. We found a 24-h cycle in seven of
      the 10 patients. One patient had a 6-h, one a 12-h, and one a 63-h cycle. The
      mean value of the cosine curve in the respective optimum cycles was 36.48 +/-
      0.34  degrees C, and the amplitude was 0.22 +/- 0.09  degrees C. Of the seven
      subjects with 24-h cycles, the highest body temperature occurred between 12:58
      and 14:44 h in four. In addition to 24-h cycles of core temperature rhythm, short
      cycles of 12 and 6-h and a long cycle of 63-h were seen. In order to understand
      the temperature rhythms of bedridden elderly patients with DOC, it is necessary
      to monitor their core body temperatures, ideally using a simple, non-invasive
      device. In the future, it will be important to investigate the relationship of
      the core temperature rhythm to nursing care and living environment.

PMID- 23866793
TI  - Critical incidents in a tertiary care clinic for internal medicine.
AB  - BACKGROUND: Reducing medical errors has become an international concern.
      Population-based studies consistently demonstrate inacceptable high rates of
      medical injury and preventable deaths. Thus, electronic critical incident
      reporting systems are now increasingly used in hospitals, predominantly in
      anesthesia. However, studies systematically analyzing critical incidents are
      scarce. Our aim was to describe content and causes of critical incidents in our
      Clinic for Internal Medicine. RESULTS: We retrospectively analyzed all critical
      incidents reported during a 54-months period. Between implementation and
      analysis, 456 incidents were reported anonymously in the commercially available
      platform-independent, web-based critical incident reporting system. All incidents
      were analyzed according to the reporting profession, time point during
      hospitalization process, content and potential causes.Most incidents occurred on
      medical wards (80%). The most frequent type of incidents was medication errors
      (62%). These incidents primarily occurred when prescribing and/or administering
      drugs (30% and 29% of medication errors respectively). So-called, human errors',
      i.e. occurring without apparent external factor, were the most frequently
      indicated cause of critical incidents (56%) followed by insufficient
      communication (26%). These problems primarily occurred between different groups
      of health care professionals and between different departments. The described
      types and reasons of critical incidents remained stable during the observation
      period. CONCLUSIONS: The findings of our analysis of the character and type of
      critical incidents occurring in a tertiary care clinic for internal medicine
      reported in an anonymous, voluntary, electronic reporting system suggest that
      strategies to improve communication and medication delivery are most promising to
      avoid critical incidents.

PMID- 23866792
TI  - Transplantation of human fetal-derived neural stem cells improves cognitive
      function following cranial irradiation.
AB  - Treatment of central nervous system (CNS) malignancies typically involves
      radiotherapy to forestall tumor growth and recurrence following surgical
      resection. Despite the many benefits of cranial radiotherapy, survivors often
      suffer from a wide range of debilitating and progressive cognitive deficits.
      Thus, while patients afflicted with primary and secondary malignancies of the CNS
      now experience longer local regional control and progression-free survival, there
      remains no clinical recourse for the unintended neurocognitive sequelae
      associated with their cancer treatments. Multiple mechanisms contribute to
      disrupted cognition following irradiation, including the depletion of
      radiosensitive populations of stem and progenitor cells in the hippocampus. We
      have explored the potential of using intrahippocampal transplantation of human
      stem cells to ameliorate radiation-induced cognitive dysfunction. Past studies
      demonstrated the capability of cranially transplanted human embryonic (hESCs) and
      neural (hNSCs) stem cells to functionally restore cognition in rats 1 and 4
      months after cranial irradiation. The present study employed an FDA-approved
      fetal-derived hNSC line capable of large scale-up under good manufacturing
      practice (GMP). Animals receiving cranial transplantation of these cells 1 month
      following irradiation showed improved hippocampal spatial memory and contextual
      fear conditioning performance compared to irradiated, sham surgery controls.
      Significant newly born (doublecortin positive) neurons and a smaller fraction of
      glial subtypes were observed within and nearby the transplantation core.
      Engrafted cells migrated and differentiated into neuronal and glial subtypes
      throughout the CA1 and CA3 subfields of the host hippocampus. These studies
      expand our prior findings to demonstrate that transplantation of fetal-derived
      hNSCs improves cognitive deficits in irradiated animals, as assessed by two
      separate cognitive tasks. 

PMID- 23866794
TI  - Establishing a health information workforce: innovation for low- and middle
      income countries.
AB  - BACKGROUND: To address the shortage of health information personnel within
      Botswana, an innovative human resources approach was taken. University graduates
      without training or experience in health information or health sciences were
      hired and provided with on-the-job training and mentoring to create a new cadre
      of health worker: the district Monitoring and Evaluation (M&E) Officer. This
      article describes the early outcomes, achievements, and challenges from this
      initiative. METHODS: Data were collected from the district M&E Officers over a 2
      year period and included a skills assessment at baseline and 12 months, pre- and
      post-training tests, interviews during stakeholder site visits, a survey of
      achievements, focus group discussions, and an attrition assessment. RESULTS: An
      average of 2.7 mentoring visits were conducted for M&E Officers in each district.
      There were five training sessions over 18 months. Knowledge scores significantly
      increased (p < 0.05) during the three trainings in which pre/post tests were
      administered. Over 1 year, there were significant improvements (p < 0.05) in self
      rated skills related to computer literacy, checking data validity, implementing
      data quality procedures, using data to support program planning, proposing
      indicators, and writing M&E reports. Out of the 34 district M&E Officers
      interviewed during site visits, most were conducting facility visits to review
      data (27/34; 79%), comparing data sets over time (31/34; 91%), backing up data
      (32/34; 94%), and analyzing data (32/34; 94%). Common challenges included late
      facility reports (28/34; 82%), lack of transportation (22/34; 65%), inaccurate
      facility reports (10/34; 29%), and colleagues' misunderstanding of M&E (10/34;
      29%). Six posts were vacated in the first year (6/51; 12%). A total of 49
      Officers completed the achievements survey; of these, common accomplishments
      related to improvements in data management (35/49; 71%), data quality (31/49;
      63%), data use (29/49; 59%), and capacity development (26/49; 53%). CONCLUSIONS:
      The development of a cadre of district M&E Officers has contributed positively to
      the health information system in Botswana. In the absence of tertiary training
      related to health information, on-the-job training and mentoring of university
      graduates can be an effective approach for developing a new professional cadre of
      M&E expertise and for strengthening capacity within a national health system.

PMID- 23866795
TI  - Macronutrient intake and type 2 diabetes risk in middle-aged Australian women.
      Results from the Australian Longitudinal Study on Women's Health.
AB  - OBJECTIVE: To investigate the association between macronutrient intake and type 2
      diabetes risk in middle-aged Australian women. DESIGN: A prospective cohort
      study, with 6 years (2002-2007) of follow up. Dietary intake was assessed with a
      validated FFQ. Relative risks with 95 % confidence intervals were used to examine
      risk associations. SETTING: Australian Longitudinal Study on Women's Health,
      Australia. SUBJECTS: Australian women (n 8370) from the Australian Longitudinal
      Study on Women's Health aged 45-50 years and free of type 2 diabetes at baseline.
      RESULTS: After 6 years of follow-up, 311 women developed type 2 diabetes. After
      adjusting for sociodemographic, lifestyle and other dietary risk factors, MUFA,
      total n-3 PUFA, alpha-linolenic acid and total n-6 PUFA intakes were positively
      associated with the incidence of type 2 diabetes. The relative risks for type 2
      diabetes for the highest compared with the lowest quintiles were 1.64 (95 % CI
      1.06, 2.54), P = 0.04 for MUFA; 1.55 (95 % CI 1.03, 2.32), P = 0.01 for n-3 PUFA;
      1.84 (95 % CI 1.25, 2.71), P < 0.01 for alpha-linolenic acid; and 1.60 (95 % CI
      1.03, 2.48), P = 0.04 for n-6 PUFA. Other dietary macronutrients were not
      significantly associated with diabetes risk. CONCLUSIONS: The data indicate that
      consumption of MUFA, n-3 PUFA and n-6 PUFA may influence the risk of developing
      type 2 diabetes in women.

PMID- 23866796
TI  - Health education interventions to raise awareness of rheumatic fever: a
      systematic review protocol.
AB  - BACKGROUND: There is a significant global health burden associated with acute
      rheumatic fever (ARF) and rheumatic heart disease (RHD), especially in developing
      countries. ARF and RHD most often strike children and young adults living in
      impoverished settings, where unhygienic conditions and lack of awareness and
      knowledge of streptococcal infection progression are common. Secondary
      prophylactic measures have been recommended in the past, but primary prevention
      measures have been gaining more attention from researchers frustrated by the
      perpetual prevalence of ARF and RHD in developing countries. Health education
      aims to empower people to take responsibility for their own well-being by gaining
      control over the underlying factors that influence health. We therefore conducted
      a review of the current best evidence for the use of health education
      interventions to increase awareness and knowledge of streptococcal pharyngitis
      and ARF. METHODS AND DESIGN: This article describes the protocol for a systematic
      review of the effectiveness of health education interventions aimed at increasing
      awareness and knowledge of the symptoms, causes and consequences of streptococcal
      pharyngitis, rheumatic fever and/or rheumatic heart disease. Studies will be
      selected in which the effect of an intervention is compared with either a pre
      intervention or a control, targeting all possible audience types. Primary and
      secondary outcomes of interest are pre-specified. Randomized controlled trials,
      quasi-randomized trials, controlled before-after studies and controlled clinical
      trials will be considered. We will search several bibliographic databases (for
      example, PubMed, EMBASE, World Health Organization Library databases, Google
      Scholar) and search sources for gray literature. We will meta-analyze included
      studies. We will conduct subgroup analyses according to intervention subtypes:
      printed versus audiovisual and mass media versus training workshops. DISCUSSION:
      This review will provide evidence for the effectiveness of educational components
      in health promotion interventions in raising public awareness in regard to the
      symptoms, causes and consequences of streptococcal pharyngitis, ARF and/or RHD.
      Our results may provide guidance in the development of future intervention
      studies and programs.

PMID- 23866797
TI  - The prognostic value of the number of negative lymph nodes in esophageal cancer
      patients after transthoracic resection.
AB  - BACKGROUND: Although the number of positive lymph nodes (LN), the total number of
      resected LN, and the proportion of positive LN have been reported to be
      associated with survival in patients with esophageal cancer, little is known
      about the prognostic impact of the number of negative LN. METHODS: A
      retrospective review of 754 patients receiving transthoracic esophagectomy for
      cancer between January 1995 and September 2011 was performed. The prognostic
      impact of the number of negative LN was analyzed. Log rank testing was used to
      compare survival curves, and Cox regression analysis was performed to identify
      significant prognostic factors. RESULTS: A total of 707 patients were included.
      The mean follow-up time was 28.4+/-30.9 months. The 5-year overall survival for
      the entire cohort was 30.1%. Patients with a high number of negative LN (>=19)
      had better overall survival than patients with a low number of negative LN (5
      year survival rate 33.4% versus 26.4%, p=0.005). Stratified analysis showed that
      the impact of the number of negative LN was significant in patients with T3/4
      (p=0.027) and node-positive (p=0.002) esophageal cancers but not in patients with
      less advanced tumors. Multivariate Cox regression analysis demonstrated that the
      number of negative LN (in addition to age, sex, T stage, N stage, tumor length,
      and surgical approach) was an independent prognostic factor. CONCLUSIONS: A
      higher number of negative LN is associated with better overall survival of
      esophageal cancer patients after resection. The correlation of a high number of
      negative LN (>=19) with survival was more prominent in patients with advanced
      (T3/4 stage, node-positive) tumors.

PMID- 23866798
TI  - Cognitive outcomes 7.5 years after angioplasty compared with off-pump coronary
      bypass surgery.
AB  - BACKGROUND: Off-pump coronary artery bypass grafting and percutaneous coronary
      intervention are both associated with cognitive decline, but limited data are
      available on long-term outcomes. This study compared long-term cognitive outcomes
      between patients managed with percutaneous coronary intervention and off-pump
      coronary artery bypass grafting. METHODS: A multicenter trial in the Netherlands
      randomized 280 patients to percutaneous coronary intervention or off-pump
      coronary artery bypass grafting. Cognitive performance 7.5 years after
      randomization was assessed through a battery of 9 neuropsychologic tests and
      summarized into a combined Z-score. RESULTS: After 7.5 years, cognitive
      assessment could be performed in 81% of the 249 surviving patients. Better
      cognitive performance was observed in the off-pump coronary artery bypass
      grafting group (combined Z-score 0.11 for off-pump coronary artery bypass
      grafting versus -0.17 for percutaneous coronary intervention; difference 0.28,
      95% confidence interval 0.08 to 0.47, p < 0.01). However, this difference became
      nonsignificant (Z-score difference 0.14, 95% confidence interval -0.01 to 0.29, p
      = 0.08) after multivariable adjustment for potential confounders. CONCLUSIONS: At
      7.5 years follow-up, off-pump coronary artery bypass grafting patients had a
      similar or perhaps even better cognitive performance compared with percutaneous
      coronary intervention patients.

PMID- 23866799
TI  - Surgical treatment and prognosis of thymic squamous cell carcinoma: a
      retrospective analysis of 105 cases.
AB  - BACKGROUND: Thymic squamous cell carcinomas are rare malignancies with limited
      information regarding results of surgery therapy. The objective of the current
      study was to evaluate their clinical and pathologic features and possible
      prognostic factors. METHODS: From February 2003 to December 2010, 105 consecutive
      surgical patients were enrolled in this study with pathologic confirmed thymic
      squamous cell carcinoma in Shanghai Chest Hospital. Clinical and pathologic data
      were retrospectively reviewed. Survival analysis was performed using the Kaplan
      Meier and log rank tests. Multivariate analysis was performed using the Cox
      regression model. RESULTS: The squamous cell subtype made up 73.4% of the thymic
      carcinomas and 16.1% of total thymic tumors. Four patients (3.8%) presented with
      myasthenia gravis. The 5-year overall survival rate and the disease-free survival
      rate were 59.5% and 57.6%, respectively. On multivariate analysis, only the
      completeness of resection (hazard ratio 3.692; 95% confidence interval: 1.827 to
      7.464; p=0.001) was found to have significant impact on overall survival.
      Completeness of resection (hazard ratio 2.361; 95% confidence interval: 1.226 to
      4.547; p=0.010) and chemotherapy (hazard ratio 0.307; 95% confidence interval:
      0.134 to 0.704; p=0.005) were associated with disease-free survival. CONCLUSIONS:
      Complete resection not only predicts better overall survival but also extends
      disease-free interval after resection of thymic squamous cell carcinoma. Our
      results provide additional evidence supporting an alternative clinical stage
      specific for thymic carcinoma.

PMID- 23866800
TI  - Primary endpoints of the biventricular pacing after cardiac surgery trial.
AB  - BACKGROUND: This study sought to determine whether optimized biventricular pacing
      increases cardiac index in patients at risk of left ventricular dysfunction after
      cardiopulmonary bypass. Procedures included coronary artery bypass, aortic or
      mitral surgery and combinations. This trial was approved by the Columbia
      University Institutional Review Board and was conducted under an Investigational
      Device Exemption. METHODS: Screening of 6,346 patients yielded 47 endpoints. With
      informed consent, 61 patients were randomized to pacing or control groups.
      Atrioventricular and interventricular delays were optimized 1 (phase I), 2 (phase
      II), and 12 to 24 hours (phase III) after bypass in all patients. Cardiac index
      was measured by thermal dilution in triplicate. A 2-sample t test assessed
      differences between groups and subgroups. RESULTS: Cardiac index was 12% higher
      (2.83+/-0.16 [standard error of the mean] vs 2.52+/-0.13 liters/minute/square
      meter) in the paced group, less than predicted and not statistically significant
      (p=0.14). However, when aortic and aortic-mitral surgery groups were combined,
      cardiac index increased 29% in the paced group (2.90+/-0.19, n=14) versus
      controls (2.24+/-0.15, n=11) (p=0.0138). Using a linear mixed effects model, t
      test revealed that mean arterial pressure increased with pacing versus no pacing
      at all optimization points (phase I 79.2+/-1.7 vs 74.5+/-1.6 mm Hg, p=0.008;
      phase II 75.9+/-1.5 vs 73.6+/-1.8, p=0.006; phase III 81.9+/-2.8 vs 79.5+/-2.7,
      p=0.002). CONCLUSIONS: Cardiac index did not increase significantly overall but
      increased 29% after aortic valve surgery. Mean arterial pressure increased with
      pacing at 3 time points. Additional studies are needed to distinguish rate from
      resynchronization effects, emphasize atrioventricular delay optimization, and
      examine clinical benefits of temporary postoperative pacing.

PMID- 23866801
TI  - Long-term fate of patients discharged to extended care facilities after
      cardiovascular surgery.
AB  - BACKGROUND: The Society of Thoracic Surgeons predictive algorithms can be used to
      help patients understand the risks in having a surgical procedure. However,
      elderly patients are frequently more concerned about the quality of their
      remaining life and whether they will return home. Currently, we have no
      predictors of which patients are likely to return to independent living after
      surgery. We followed patients discharged home or to an extended care facility to
      determine which patients were most likely to return home and be alive at one
      year. METHODS: This single-hospital, retrospective study followed 590 cardiac
      surgery patients (January 2008 to December 2009) for at least 1 year after
      discharge. Follow-up data were collected by contacting facilities, patients, and
      families, and Social Security Death Index searches. RESULTS: At hospital
      discharge, 84.4% went home, 3.7% to rehab, 7.5% to skilled nursing facilities
      (SNF), and 4.4% to a long-term acute care facility (LTAC). Predictors for
      facility discharge include increasing age, female, dialysis, emergent status,
      procedures other than CAB, preoperative stroke, and moderate to severe tricuspid
      insufficiency. The most significant predictors of dying or still being in a
      facility at 1 year include being on dialysis, right heart failure, and having
      chronic lung disease. Considering perioperative complications, requiring
      prolonged ventilation decreases the odds of being home and alive at 1 year by
      67%: one-year survival at home, 95.4%; rehabilitation, 63.6%; SNF, 52.3%; and
      LTAC, 30.8%. CONCLUSIONS: Many patients discharged to extended care do not return
      to their previous lifestyle; only 30.8% of those requiring care in a LTAC
      facility are alive at home at 1 year.

PMID- 23866802
TI  - Does external pleural suction reduce prolonged air leak after lung resection?
      Results from the AirINTrial after 500 randomized cases.
AB  - BACKGROUND: External pleural suction is used after lung resection to promote lung
      expansion and minimize air leak duration. Published randomized trials failed to
      prove this advantage but they are limited in number and underpowered in many
      cases. The aim of the AirINTrial study was to test the hypothesis that external
      pleural suction may reduce the rate of prolonged air leak in a large, randomized
      cohort. METHODS: All candidates for lung resection (with the exception of
      pneumonectomy) were considered eligible for this single-center study. At the end
      of operation, patients were stratified by the type of resection (anatomic versus
      nonanatomic) and randomly allocated into the external suction arm (-15 cmH2O,
      group A) or into the no external suction arm (control arm, group B) in a 1:1
      ratio. Chest drains were maintained for 3 days and then they were either removed
      or connected to an Heimlich valve, when an air leak was present. The main
      endpoint was to compare groups in terms of prolonged air leak (defined as the
      rate of patients having a chest drain still in place by postoperative day 7).
      RESULTS: Starting on February 2011, 500 patients were randomized over a 21-month
      period, 250 in group A and 250 in group B. Twenty-one patients in group B (8.4%)
      required pleural suction owing to large pneumothorax or diffuse subcutaneous
      emphysema. On postoperative day 7, the chest drain was still in place in 25
      patients in group A and in 34 patients in group B (10% and 14%, respectively; p =
      0.2). Subgroup analysis showed that external pleural suction reduced the
      prolonged air leak rate in the subgroup of patients who underwent anatomic
      resection (n = 296, 9.6% in group A and 16.8% in group B; p = 0.05). CONCLUSIONS:
      Results from the AirINTrial showed that the routine use of external suction
      reduces the rate of prolonged air leak after anatomic lung resection. More
      accurate strategies of pleural suction based on the amount of air flow and the
      degree of lung expansion should be probably established to improve its
      effectiveness.

PMID- 23866803
TI  - Transvalvular pacemaker leads increase the recurrence of regurgitation after
      tricuspid valve repair.
AB  - BACKGROUND: The impact of a transvalvular pacemaker lead on the progression of
      tricuspid regurgitation (TR) after tricuspid valve (TV) repair has not been
      clearly demonstrated. The aim of this study was to evaluate the presence of a
      transvalvular pacemaker lead as a risk factor for TR after TV repair in a large
      patient cohort. METHODS: A retrospective review included 791 patients who
      underwent TV repair at our institution from 1977 to 2008. All patients bearing a
      transvenous pacemaker implanted either preoperatively or within 30 days of
      surgery were categorized in the "PACE" group (n=176), the remaining patients were
      categorized in the "NO PACE" group (n=615). RESULTS: Mean age was 61+/-11 years,
      and 575 patients (73%) were female. Mean follow-up was 5.8+/-5.5 years. Operative
      mortality was 13%. At discharge, TR severity was 3+ or greater in 10% and 15% of
      patients in the PACE and NO PACE groups, respectively (p=0.19). Multivariate
      analysis using a Cox regression model identified the presence of a transvenous
      pacemaker as an independent risk factor for recurrence of TR 2+ or greater
      (hazard ratio [HR] 1.60, p=0.008) and TR 3+ or greater (HR 1.47, p=0.046) at last
      follow-up. The presence of a transvenous pacemaker was also a significant
      independent predictor of late mortality (HR 2.12, p=0.02). CONCLUSIONS: In
      patients undergoing tricuspid valve surgery, the presence of a transvenous
      pacemaker implanted either preoperatively or within 30 days of surgery is
      associated with a significantly increased risk of persistent or recurrent TR at
      late follow-up.

PMID- 23866804
TI  - Variation in coronary anatomy in adult patients late after arterial switch
      operation: a computed tomography coronary angiography study.
AB  - BACKGROUND: The arterial switch operation is the current treatment for
      transposition of the great arteries. Long-term outcome mainly depends on the
      patency of the transferred coronary arteries. This study assessed the presence of
      abnormal coronary findings and neoaortic root dilation late after arterial switch
      operation. METHODS: In 30 adult patients after arterial switch operation (22 men,
      22 +/- 3 years), computed tomography angiography was performed to assess the
      coronary anatomy and abnormal coronary findings, defined as significant stenosis,
      interarterial coronary course, and acute angled coronary origins. Neoaortic root
      dimensions and coronary takeoff height were also assessed. RESULTS: The most
      common coronary anatomy pattern was found in 24 of 30 patients. Variant anatomy
      patterns were seen in 6 patients (5 with aberrant circumflex artery, 1 with a
      single ostium). The prevalence of abnormal coronary findings was higher in
      patients with variant coronary pattern as compared with patients with common
      coronary pattern (100% and 29%, respectively; p = 0.003). In particular, an acute
      angle of the coronary origin was frequently observed. In patients with an acute
      angle, larger dimensions of the aortic annulus (p = 0.016) and the sinus of
      Valsalva (p = 0.002) were observed. Moreover, a higher takeoff of the right (p =
      0.030) and left (p = 0.002) coronary ostium was noted in patients with acute
      angles. CONCLUSIONS: Abnormal coronary findings were frequently observed in adult
      patients after arterial switch operation, especially in patients with a variant
      coronary anatomy pattern. Neoaortic root dilation and a higher coronary takeoff
      may explain part of the pathophysiology. Long-term follow-up is needed to
      determine the clinical significance of these findings.

PMID- 23866805
TI  - Minimally invasive and conventional aortic valve replacement: a propensity score
      analysis.
AB  - BACKGROUND: The study aimed to compare the short-term results of aortic valve
      replacement through minimally invasive and sternotomy approaches. METHODS: This
      is a retrospective, observational, cohort study of prospectively collected data
      on 709 patients undergoing isolated primary aortic valve replacement between 2004
      and 2011. Of these, 338 were performed through either right anterior
      minithoracotomy or upper ministernotomy. With propensity score matching, 182
      patients (minimally invasive group) were compared with 182 patients in
      conventional sternotomy (control group). RESULTS: After propensity matching, the
      2 groups were comparable in terms of preoperative characteristics.
      Cardiopulmonary bypass time (117.5 vs 104.1 min, p<0.0001) and aortic cross
      clamping time (83.8 vs 71.3 min, p<0.0001) were longer in the minimally invasive
      group, with no difference in length of stay (median 6 vs 5 days, p=0.43), but
      shorter assisted ventilation time (median 8 vs 7 hours, p=0.022). Overall in
      hospital mortality was identical between the groups (1.64 vs 1.64%, p=1.0). No
      difference in the incidence of major and minor postoperative complications and
      related morbidity was observed. Minimally invasive aortic valve replacement was
      associated with a lower incidence of new onset postoperative atrial fibrillation
      (21% vs 31%, p=0.04). Reduction of the complication rate was observed. Median
      transfusion pack per patient was higher in the control group (2 vs 1 units,
      p=0.04). CONCLUSIONS: Our experience shows that mini-access isolated aortic valve
      surgery is a reproducible, safe, and effective procedure and reduces assisted
      ventilation duration, the need for blood product transfusion, and incidence of
      post-surgery atrial fibrillation.

PMID- 23866806
TI  - Revascularization for the right coronary artery territory in off-pump coronary
      artery bypass surgery.
AB  - BACKGROUND: Graft selection for the right coronary artery territory remains
      controversial. The objective of this study was to analyze outcomes from
      revascularization of the right coronary artery territory using the right internal
      thoracic artery (RITA), the right gastroepiploic artery (RGEA), or a saphenous
      vein graft (SVG). METHODS: Between January 2001 and December 2010, 1,434 patients
      who underwent off-pump coronary artery bypass surgery using the bilateral mammary
      arteries were enrolled. Propensity score analysis was used to match patients who
      underwent revascularization of the right coronary artery territory with the RITA
      in a Y-composite fashion (RITA group, n=292), the RGEA (RGEA group, n=292), and
      the SVG (SVG group, n=292). Clinical and angiographic data were analyzed.
      RESULTS: There were no intergroup differences in terms of in-hospital mortality
      (0.3% [1 of 292], 0% [0 of 292], and 1% [3 of 292], p=0.332). Freedom from major
      adverse events including death, stoke, myocardial infarction, and reintervention
      at 10 years was similar among the three groups (87.8%+/-3.0% in the RITA group
      versus 92.4%+/-1.7% in the RGEA group versus 86.7%+/-3.4% in the SVG group;
      p=0.466). A stratified regression analysis showed that use of the saphenous vein
      was predictive of graft failure (p=0.044, hazard ratio 3.9). Proximal stenosis
      (<90%) was predictive of graft failure in the arterial groups (p=0.024, hazard
      ratio 3.1), but not in the SVG group (p=0.112). CONCLUSIONS: Arterial grafts
      should be considered the first choice for right coronary artery territory
      revascularization in off-pump coronary artery bypass. However, SVG should be
      considered when proximal stenosis is less than 90%.

PMID- 23866807
TI  - Association of complications with blood transfusions in pediatric cardiac surgery
      patients.
AB  - BACKGROUND: Blood product transfusion during cardiopulmonary bypass has been
      demonstrated to be associated with increased morbidity and mortality in adult
      cardiac surgery populations. The aim of this study was to characterize the risk
      adjusted occurrence of postoperative complications and mortality in relation to
      intraoperative blood product transfusion in our pediatric cardiac surgery
      population. METHODS: A retrospective review was performed on 1,631 consecutive
      cardiopulmonary bypass cases to determine the effects of intraoperative blood
      product transfusion on selected outcomes. After adjusting for patient and
      operative risk factors, multivariate analysis was performed to determine the
      association between blood product transfusion and postoperative complications.
      Cox proportional hazards model was used to examine the relationship of packed red
      blood cell transfusion to hospital length of stay. RESULTS: Red blood cell and
      fresh frozen plasma transfusion was associated with pulmonary complications
      (adjusted odds ratio, 1.55; 95% confidence interval, 1.05 to 2.28; p=0.03). Red
      blood cell transfusion also correlated with prolonged hospital stay (p<0.01).
      Cryoprecipate transfusion was associated with postoperative pulmonary
      complications (adjusted odds ratio, 1.79; 95% confidence interval, 1.13 to 2.55;
      p=0.01), but decreased incidence of 30-day mortality (adjusted odds ratio, 0.44;
      95% confidence interval, 0.23 to 0.85; p=0.02). Platelet transfusion was
      associated with decreased 30-day mortality (adjusted odds ratio, 0.51; 95%
      confidence interval, 0.28 to 0.93; p=0.04), but not overall mortality.
      CONCLUSIONS: Blood product transfusion was associated with an increased incidence
      of postoperative pulmonary complications and prolonged hospital length of stay,
      but not overall mortality. These findings suggest that minimizing blood product
      transfusion would be beneficial in the pediatric cardiopulmonary bypass surgery
      patient population.

PMID- 23866808
TI  - Long-term survival after lobectomy for non-small cell lung cancer by video
      assisted thoracic surgery versus thoracotomy.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy for non-small cell
      lung cancer (NSCLC) is increasingly popular. However, the oncologic soundness of
      VATS for patients with NSCLC as measured by long-term survival has not been
      proven. The objective here is to determine the overall survival (OS) and disease
      free survival (DFS) in two well-matched groups of patients with NSCLC resected by
      VATS or thoracotomy. METHODS: We conducted a retrospective review of a
      prospective database to identify patients who had a lobectomy for NSCLC. A
      propensity score-matched analysis was done with variables of age, sex, smoking
      history, Charlson comorbidity index, forced expiratory volume in 1 second, lung
      diffusing capacity for carbon monoxide, histology, and clinical T and N status.
      Medical records were reviewed and survival was analyzed. RESULTS: After matching,
      there were 208 patients in each group. Patient and tumor characteristics were
      similar. The VATS group had a shorter length of stay. More nodes (14.3 versus
      11.3; p=0.001) and more nodal stations (3.8 versus 3.1; p<0.001) were removed by
      thoracotomy. No differences were seen in OS and DFS. Median follow-up was 36
      months. More than 90% of patients had clinical stage I disease, with 3- and 5
      year OS of 87.4% and 76.5%, respectively, for VATS, and 81.6% and 77.5%,
      respectively, for thoracotomy (p=0.672). Both the incidence and distribution of
      recurrence were similar. Multivariate Cox regression analyses of OS and DFS
      confirmed the noninferiority of VATS. CONCLUSIONS: For patients with clinical
      stage I NSCLC, VATS lobectomy offered similar OS and DFS compared with
      thoracotomy. Thoracotomy offers a more thorough lymph node evaluation, and may be
      appropriate for patients with more advanced clinical disease.

PMID- 23866809
TI  - Reduction of microglial activity in a model of multiple sclerosis by
      dipyridamole.
AB  - BACKGROUND: Despite extensive and persistent activation of microglia in multiple
      sclerosis (MS), microglia inhibitors have not yet been identified for treatment
      of the disorder. We sought to identify medications already in clinical use that
      could inhibit the activation of microglia. On the basis of the reported
      inhibitory effects of dipyridamole on phosphodiesterase activity that result in
      the production of various anti-inflammatory outcomes, we selected it for study.
      Dipyridamole is used clinically for secondary prevention in stroke. In this
      study, dipyridamole was examined using microglia in culture and in the mouse
      model of MS, experimental autoimmune encephalomyelitis (EAE). RESULTS: We found
      that dipyridamole attenuated the elevation of several cytokines and chemokines in
      human microglia caused by Toll-like receptor stimulation. Morphological
      characteristics of activated microglia in culture were also normalized by
      dipyridamole. In mice, dipyridamole decreased the clinical severity of EAE and
      reduced microglial activity and other histological indices of EAE in the spinal
      cord. CONCLUSIONS: Dipyridamole is an inhibitor of microglia activation and may
      have a role in MS and other neurological conditions to attenuate microglial
      activity.

PMID- 23866811
TI  - Use of virulence determinants and seropathotypes to distinguish high- and low
      risk Escherichia coli O157 and non-O157 isolates from Europe.
AB  - The presence of 10 virulence genes was examined using polymerase chain reaction
      (PCR) in 365 European O157 and non-O157 Escherichia coli isolates associated with
      verotoxin production. Strain-specific PCR data were analysed using hierarchical
      clustering. The resulting dendrogram clearly separated O157 from non-O157
      strains. The former clustered typical high-risk seropathotype (SPT) A strains
      from all regions, including Sweden and Spain, which were homogenous by Cramer's V
      statistic, and strains with less typical O157 features mostly from Hungary. The
      non-O157 strains divided into a high-risk SPTB harbouring O26, O111 and O103
      strains, a group pathogenic to pigs, and a group with few virulence genes other
      than for verotoxin. The data demonstrate SPT designation and selected PCR
      separated verotoxigenic E. coli of high and low risk to humans; although more
      virulence genes or pulsed-field gel electrophoresis will need to be included to
      separate high-risk strains further for epidemiological tracing.

PMID- 23866810
TI  - Antileptospiral activity of xanthones from Garcinia mangostana and synergy of
      gamma-mangostin with penicillin G.
AB  - BACKGROUND: Leptospirosis, one of the most widespread zoonotic infectious
      diseases worldwide, is caused by spirochetes bacteria of the genus Leptospira.
      The present study examined inhibitory activity of purified xanthones and crude
      extracts from Garcinia mangostana against both non-pathogenic and pathogenic
      leptospira. Synergy between gamma-mangostin and penicillin G against leptospires
      was also determined. METHODS: Minimal inhibitory concentrations (MIC) of crude
      extracts and purified xanthones from G. mangostana and penicillin G for a non
      pathogenic (L. biflexa serovar Patoc) and pathogenic (L. interrogans serovar
      Bataviae, Autumnalis, Javanica and Saigon) leptospires were determined by using
      broth microdilution method and alamar blue. The synergy was evaluated by
      calculating the fractional inhibitory concentration (FIC) index. RESULTS: The
      results of broth microdilution test demonstrated that the crude extract and
      purified xanthones from mangosteen possessed antileptospiral activities. The
      crude extracts were active against all five serovars of test leptospira with MICs
      ranging from 200 to >= 800 MUg/ml. Among the crude extracts and purified
      xanthones, garcinone C was the most active compound against both of pathogenic
      (MIC =100 MUg/ml) and non-pathogenic leptospira (MIC = 200 MUg/ml). However,
      these MIC values were higher than those of traditional antibiotics. Combinations
      of gamma-mangostin with penicillin G generated synergistic effect against L.
      interrogans serovars Bataviae, Autumnalis and Javanica (FIC = 0.52, 0.50, and
      0.04, respectively) and no interaction against L. biflexa serovar Patoc (FIC
      =0.75). However, antagonistic activity (FIC = 4.03) was observed in L.
      interrogans serovar Saigon. CONCLUSIONS: Crude extracts and purified xanthones
      from fruit pericarp of G. mangostana with significant antibacterial activity may
      be used to control leptospirosis. The combination of xanthone with antibiotic
      enhances the antileptospiral efficacy.

PMID- 23866812
TI  - Towards a physically more active lifestyle based on one's own values: study
      design of a randomized controlled trial for physically inactive adults.
AB  - BACKGROUND: This randomised controlled trial demonstrates the effectiveness of a
      value-based intervention program to encourage a physically more active lifestyle
      among physically inactive adults aged 30 to 50 years. The conceptual framework of
      the program is based on an innovative behavioural therapy called Acceptance and
      Commitment Therapy (ACT) that aims to increase an individual's psychological
      flexibility and support behaviour change towards a higher quality and more
      meaningful life. METHODS: Participants will be randomly allocated to a feedback
      group (FB) or an Acceptance and Commitment based (ACT+FB) group. Both the groups
      will receive written feedback about their objectively measured physical activity
      levels and offered an opportunity to attend a body composition analysis. In
      addition, the Acceptance and Commitment based group will attend six group
      sessions and be given a pedometer for self-monitoring of their daily physical
      activity throughout the 9-week intervention. The group sessions aim to clarify
      individual values and enhance committed actions towards the goal of achieving a
      more meaningful life. Participants will also be taught new skills to work on
      subjective barriers related to physical activity. Physical activity will be
      measured objectively by an accelerometer over seven consecutive days and by self
      reported questionnaires at the baseline, as well as at 3, 6, 9 and 15 months
      after the baseline measures. In addition, psychological well-being will be
      measured through the questionnaires, which assess mindfulness skills,
      psychological flexibility, psychological distress and depressive symptoms.
      DISCUSSION: This study's objective is to demonstrate a research protocol for a
      randomized controlled study motivating a physically more active lifestyle based
      on one's own values among physically inactive adults. The aim of the study is to
      evaluate the feasibility and intervention efficacy on physical activity and
      psychological well-being, and discuss challenges in motivating physically
      inactive adults towards physically more active lifestyles. TRIAL REGISTRATION:
      ClinicalTrials.gov, number NCT01796990.

PMID- 23866814
TI  - Measurement precision of the disability for back pain scale-by applying Rasch
      analysis.
AB  - BACKGROUND: The Oswestry Disability Index (ODI) is widely used for patients with
      back pain. However, few studies have examined its psychometric properties using
      modern measurement theory. The purpose of this study was to investigate the
      psychometric properties of the ODI in patients with back pain using Rasch
      analysis. METHODS: A total of 408 patients with back pain participated in this
      cross-sectional study. Patients were recruited from the orthopedic, neurosurgery,
      rehabilitation departments and pain clinic of two hospitals. Rasch analysis was
      used to examine the Chinese version of ODI 2.1 for unidimensionality, item
      difficulty, category function, differential item functioning, and test
      information. RESULTS: The fit statistics showed 10 items of the ODI fitted the
      model's expectation as a unidimensional scale. The ODI measured the different
      levels of functional limitation without skewing toward the lower or higher levels
      of disability. No significant ceiling and floor effects and gaps among the items
      were found. The reliability was high and the test information curve demonstrated
      precise dysfunction estimation. CONCLUSIONS: Our results showed that the ODI is a
      unidimensional questionnaire with high reliability. The ODI can precisely
      estimate the level of dysfunction, and the item difficulty of the ODI matches the
      person ability. For clinical application, using logits scores could precisely
      represent the disability level, and using the item difficulty could help
      clinicians design progressive programs for patients with back pain.

PMID- 23866813
TI  - A randomized controlled trial investigating the effects of PCSO-524, a patented
      oil extract of the New Zealand green lipped mussel (Perna canaliculus), on the
      behaviour, mood, cognition and neurophysiology of children and adolescents (aged
      6-14 years) experiencing clinical and sub-clinical levels of hyperactivity and
      inattention: study protocol ACTRN12610000978066.
AB  - BACKGROUND: The prevalence rate of attention-deficit/hyperactivity disorder
      (ADHD) within Western cultures is between 5% and 12%, and is the most common
      psychiatric illness among school-aged children, with an estimated 50% of these
      children retaining ADHD symptoms for the rest of their lives. Children with ADHD
      have lower blood levels of long-chain Poly Unsaturated Fatty Acids (LC PUFAs)
      compared with children without ADHD, and following PUFA supplementation, have
      shown improvements in ADHD-related symptoms. One highly promising marine based LC
      PUFA preparation is the Omega-3-rich Lyprinol/Omega XL which is a natural
      formulation containing standardised lipid extract of the New Zealand green lipped
      mussel (Perna canaliculus) known as PCSO-524(r) which contains a unique
      combination of free fatty acids, sterol esters, polar lipids and carotenoids. It
      is this unique combination of marine lipids that may assist in correcting the
      decreased levels of LC PUFA levels in children with symptoms of ADHD. The
      compound is a mixture belonging to a lipid group called sterol esters (SE). The
      fatty acids in the SE fraction are mainly myristic acid, palmitic acid,
      palmitoleic acid, stearic acid, oleic acid, linoleic acid, eicosapentaenoic acid
      (EPA), and docosahexaenoic acid (DHA). Lyprinol/Omega XL has previously been
      shown to contain a potent group of Omega-3 lipids that block the 5 - lipoxygenase
      metabolic pathway responsible for inflammation in the body. METHODS: A randomized
      double blind placebo controlled trial will be utilized to assess the effects of
      14 weeks administration of Lyprinol/Omega XL versus placebo in 150 children aged
      6 to 14 years with high levels of hyperactivity and inattention. Additionally, a
      range of cognitive, mood and central electrophysiological measures will be
      undertaken during the 14 week supplementation trial. The primary outcome measure,
      the Conners' Parent Rating Scales will be completed initially at baseline, then
      in weeks 4, 8, 10, 14 and then again at 4 weeks post-administration (week 18).
      The results will contribute to our understanding of the efficacy of marine based
      Omega-3 s with high anti-inflammatory actions on inattention and hyperactivity in
      children aged 6 to 14 years.

PMID- 23866816
TI  - Examining current practices.

PMID- 23866815
TI  - Comparison of high and low intensity contact between secondary and primary care
      to detect people at ultra-high risk for psychosis: study protocol for a theory
      based, cluster randomized controlled trial.
AB  - BACKGROUND: The early detection and referral to specialized services of young
      people at ultra-high risk (UHR) for psychosis may reduce the duration of
      untreated psychosis and, therefore, improve prognosis. General practitioners
      (GPs) are usually the healthcare professionals contacted first on the help
      seeking pathway of these individuals. METHODS/DESIGN: This is a cluster
      randomized controlled trial (cRCT) of primary care practices in Cambridgeshire
      and Peterborough, UK. Practices are randomly allocated into two groups in order
      to establish which is the most effective and cost-effective way to identify
      people at UHR for psychosis. One group will receive postal information about the
      local early intervention in psychosis service, including how to identify young
      people who may be in the early stages of a psychotic illness. The second group
      will receive the same information plus an additional, ongoing theory-based
      educational intervention with dedicated liaison practitioners to train clinical
      staff at each site. The primary outcome of this trial is count data over a 2-year
      period: the yield - number of UHR for psychosis referrals to a specialist early
      intervention in psychosis service - per primary care practice. DISCUSSION: There
      is little guidance on the essential components of effective and cost-effective
      educational interventions in primary mental health care. Furthermore, no study
      has demonstrated an effect of a theory-based intervention to help GPs identify
      young people at UHR for psychosis. This study protocol is underpinned by a robust
      scientific rationale that intends to address these limitations. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN70185866.

PMID- 23866818
TI  - Economic assessment of Q fever in the Netherlands.
AB  - In this paper the economic impact of controlling the Q fever epidemic in 2007
      2011 in the Netherlands is assessed. Whereas most of the long-term benefits of
      the implemented control programme stem from reduced disease burden and human
      health costs, the majority of short-term intervention costs were incurred in the
      dairy goat sector. The total intervention cost in agriculture amounted
      approximately 35,000 Euro per DALY occurred. By culling of infected animals,
      breeding prohibition and vaccination, the epidemic seems to be under control. As
      the dairy goat vaccination programme continues, future expenses in maintaining
      the current protected status are relatively low.

PMID- 23866819
TI  - Tobacco-alcohol amblyopia--nonexistent entity cannot be diagnosed.

PMID- 23866820
TI  - Update on diffusion MRI in Parkinson's disease and atypical parkinsonism.
AB  - Differentiating Parkinson's disease (PD) from other types of neurodegenerative
      atypical parkinsonism (AP) can be challenging, especially in early disease
      stages. Routine brain magnetic resonance imaging (MRI) can show atrophy or signal
      changes in several parts of the brain with fairly high specificity for particular
      forms of AP, but the overall diagnostic value of routine brain MRI is limited. In
      recent years, various advanced MRI sequences have become available, including
      diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI). Here, we
      review available literature on the value of diffusion MRI for identifying and
      quantifying different patterns of neurodegeneration in PD and AP, in relation to
      what is known of underlying histopathologic changes and clinical presentation of
      these diseases. Next, we evaluate the value of diffusion MRI to differentiate
      between PD and AP and the potential value of serial diffusion MRI to monitor
      disease progression. We conclude that diffusion MRI may quantify patterns of
      neurodegeneration which could be of additional value in clinical use. Future
      prospective clinical cohort studies are warranted to assess the added diagnostic
      value of diffusion MRI. 

PMID- 23866821
TI  - YouTube as a source of information on rhinosinusitis: the good, the bad and the
      ugly.
AB  - OBJECTIVE: YouTube is an internet-based repository of user-generated content.
      This study aimed to determine whether YouTube represented a valid and reliable
      patient information resource for the lay person on the topic of rhinosinusitis.
      METHODS: The study included the first 100 YouTube videos found using the search
      term 'sinusitis'. Videos were graded on their ability to inform the lay person on
      the subject of rhinosinusitis. RESULTS: Forty-five per cent of the videos were
      deemed to provide some useful information. Fifty-five per cent of the videos
      contained little or no useful facts, 27 per cent of which contained potentially
      misleading or even dangerous information. Videos uploaded by medical
      professionals or those from health information websites contained more useful
      information than those uploaded by independent users. CONCLUSION: YouTube appears
      to be an unreliable resource for accurate and up to date medical information
      relating to rhinosinusitis. However, it may provide some useful information if
      mechanisms existed to direct lay people to verifiable and credible sources.

PMID- 23866822
TI  - High-fidelity national carbon mapping for resource management and REDD+.
AB  - BACKGROUND: High fidelity carbon mapping has the potential to greatly advance
      national resource management and to encourage international action toward climate
      change mitigation. However, carbon inventories based on field plots alone cannot
      capture the heterogeneity of carbon stocks, and thus remote sensing-assisted
      approaches are critically important to carbon mapping at regional to global
      scales. We advanced a high-resolution, national-scale carbon mapping approach
      applied to the Republic of Panama - one of the first UN REDD + partner countries.
      RESULTS: Integrating measurements of vegetation structure collected by airborne
      Light Detection and Ranging (LiDAR) with field inventory plots, we report LiDAR
      estimated aboveground carbon stock errors of ~10% on any 1-ha land parcel across
      a wide range of ecological conditions. Critically, this shows that LiDAR provides
      a highly reliable replacement for inventory plots in areas lacking field data,
      both in humid tropical forests and among drier tropical vegetation types. We then
      scale up a systematically aligned LiDAR sampling of Panama using satellite data
      on topography, rainfall, and vegetation cover to model carbon stocks at 1-ha
      resolution with estimated average pixel-level uncertainty of 20.5 Mg C ha-1
      nationwide. CONCLUSIONS: The national carbon map revealed strong abiotic and
      human controls over Panamanian carbon stocks, and the new level of detail with
      estimated uncertainties for every individual hectare in the country sets Panama
      at the forefront in high-resolution ecosystem management. With this repeatable
      approach, carbon resource decision-making can be made on a geospatially explicit
      basis, enhancing human welfare and environmental protection.

PMID- 23866824
TI  - The role of alloresponsive Ly49+ NK cells in rat islet allograft failure in the
      presence and absence of cytomegalovirus.
AB  - There are still many factors to discover to explain the low success rates of
      islet allografts. In this study, we demonstrate that specific subpopulations of
      alloreactive NK cells may be involved in the failure of islet allografts. By
      performing allotransplantation in rats (n = 13), we observed peripheral expansion
      and infiltration of alloreactive Ly49i2(+) NK cells in the grafts. An effective
      strategy in rats to enhance the expansion of Ly49i2(+) NK cells is performing a
      rat cytomegalovirus infection (n = 6). Cytomegalovirus infection was associated
      with an early expansion of the Ly49i2(+) NK cells and accelerated islet graft
      failure. The Ly49i2(+) NK cells are both alloreactive and involved in virus
      clearance. The expansion of this subpopulation could not be blocked by
      cyclosporin A immunosuppression. Also alloreactive KLRH1(+) NK cells infiltrated
      the grafts, but nonalloreactive NKR-P1B(+) cells were not observed in the islet
      allografts. Perforin staining of the infiltrating NK cells demonstrated the
      cytotoxic capacity of these cells. Our data suggest a role for this NK
      subpopulation in rat islet allograft destruction. 

PMID- 23866823
TI  - Effects of benralizumab on airway eosinophils in asthmatic patients with sputum
      eosinophilia.
AB  - BACKGROUND: Many asthmatic patients exhibit sputum eosinophilia associated with
      exacerbations. Benralizumab targets eosinophils by binding IL-5 receptor alpha,
      inducing apoptosis through antibody-dependent cell-mediated cytotoxicity.
      OBJECTIVES: We sought to evaluate the safety of benralizumab in adults with
      eosinophilic asthma and its effects on eosinophil counts in airway
      mucosal/submucosal biopsy specimens, sputum, bone marrow, and peripheral blood.
      METHODS: In this multicenter, double-blind, placebo-controlled phase I study, 13
      subjects were randomized to single-dose intravenous placebo or 1 mg/kg
      benralizumab (day 0; cohort 1), and 14 subjects were randomized to 3 monthly
      subcutaneous doses of placebo or 100 or 200 mg of benralizumab (days 0, 28, and
      56; cohort 2). Cohorts 1 and 2 were consecutive. RESULTS: The incidence of
      adverse events was similar between groups. No serious adverse events related to
      benralizumab occurred. In cohort 1 intravenous benralizumab produced a median
      decrease from baseline of 61.9% in airway mucosal eosinophil counts (day 28;
      placebo: +19.6%; P = .28), as well as an 18.7% decrease (day 21) in sputum and a
      100% decrease (day 28) in blood counts. Eosinophils were not detectable in bone
      marrow of benralizumab-treated subjects (day 28, n = 4). In cohort 2 subcutaneous
      benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in
      airway eosinophil counts (day 84; placebo, 46.7%; P = .06), as well as an 89.9%
      decrease (day 28) in sputum and a 100% decrease (day 84) in blood counts.
      CONCLUSION: Single-dose intravenous and multiple-dose subcutaneous benralizumab
      reduced eosinophil counts in airway mucosa/submucosa and sputum and suppressed
      eosinophil counts in bone marrow and peripheral blood. The safety profile
      supports further development. Additional studies are needed to assess the
      clinical benefit in asthmatic patients.

PMID- 23866825
TI  - Systemic administration of 3-bromopyruvate reveals its interaction with serum
      proteins in a rat model.
AB  - BACKGROUND: 3-bromopyruvate (3-BrPA) is a glycolytic inhibitor that affects
      cancer cells by targeting energy metabolism. Preclinical reports have established
      that a 1.75 mM dose of 3-BrPA is effective and sufficient to inhibit tumor growth
      when administered under a loco-regional approach (intraarterial and
      intratumoral). This loco-regional therapeutic dose was found to be nontoxic when
      given systemically as well. Yet, the mechanism underlying this lack of toxicity
      of 1.75 mM 3-BrPA during systemic delivery is unknown. Here, we investigated the
      mechanism associated with the lack of organ toxicity when 1.75 mM 3-BrPA was
      administered systemically using radiolabeled (14C)-3-BrPA in Sprague-Dawley rats.
      FINDINGS: Data obtained from tissue-autoradiography of rats infused with 14C-3
      BrPA showed strong 14C-signal in tissue sections of various organs except the
      brain corroborating that 3-BrPA does not cross the blood-brain barrier.
      Significantly, Hematoxylin & Eosin staining and apoptosis assay of tissue
      sections positive for 14C-signal showed no signs of toxicity or apoptosis.
      Convincingly, the 14C-signal observed in tissue-autoradiography emanates from 3
      BrPA that is non-reactive or non-toxic, hence we further investigated whether the
      lack of toxicity is due to its interaction or alkylation with serum components.
      Analysis of serum proteins by 1D and 2D-gel electrophoretic autoradiography
      showed that 14C-BrPA selectively binds to peptides of molecular mass ~50-60 kDa.
      Mass spectrometry data suggested that 14C-BrPA could interact with alpha1
      antitrypsin and a peptide of albuminoid-family. CONCLUSION: Our data indicate
      that selective interaction of 3-BrPA with serum proteins could contribute to the
      apparent lack of tissue-toxicity at the indicated close when the drug is given
      systematically in Sprague-Dawley rats.

PMID- 23866826
TI  - Cross sectional analysis of the association between mode of school transportation
      and physical fitness in children and adolescents.
AB  - OBJECTIVE: To investigate the associations between body composition,
      cardiorespiratory and muscular fitness in relation to travel mode to school in
      children and adolescents. METHOD: Children and adolescents from 40 elementary
      schools and 23 high schools representing all regions in Norway were invited to
      participate in the study. Anthropometry, cardiorespiratory and muscular fitness
      were tested at the school location. Questionnaires were used in order to register
      mode of transport to school, age, gender and levels of leisure time physical
      activity. RESULTS: A total of 1694 (i.e. 60% of all invited participants)
      children and adolescents at a mean age of 9.6 and 15.6 respectively (SD = 0.4 for
      both groups) were analyzed for associations with physical fitness variables.
      Males cycling to school had lower sum of skin folds than adolescents walking to
      school. Higher cardiorespiratory fitness in adolescents and male cyclists
      compared to walkers and passive commuters were observed. Among children, cycling
      and walking to school, higher isometric muscle endurance in the back extensors
      compared to passive commuters was observed. CONCLUSION: Based on this national
      representative cross-sectional examination of randomly selected children and
      adolescents there is evidence that active commuting, especially cycling, is
      associated with a favourable body composition and better cardiorespiratory and
      muscular fitness as compared to passive commuting.

PMID- 23866827
TI  - Food choice, plate waste and nutrient intake of elementary- and middle-school
      students participating in the US National School Lunch Program.
AB  - OBJECTIVE: To (i) evaluate food choices and consumption patterns of elementary-
      and middle-school students who participate in the National School Lunch Program
      (NSLP) and (ii) compare students' average nutrient intake from lunch with NSLP
      standards. DESIGN: Plate waste from elementary- and middle-school students' lunch
      trays was measured in autumn 2010 using a previously validated digital
      photography method. Percentage waste was estimated to the nearest 10 % for the
      entree, canned fruit, fresh fruit, vegetable, grain and milk. Univariate ANOVA
      determined differences in percentage waste between schools, grades and genders.
      Daily nutrient intake was calculated using the district's menu analysis and
      percentage waste. SETTING: Elementary and middle schools in northern Colorado
      (USA). SUBJECTS: Students, grades 1-8. RESULTS: Plate waste was estimated from
      899 lunch trays; 535 elementary- and 364 middle-school students. Only 45 % of
      elementary- and 34 % middle-school students selected a vegetable. Elementary
      school students wasted more than a third of grain, fruit and vegetable menu
      items. Middle-school students left nearly 50 % of fresh fruit, 37 % of canned
      fruit and nearly a third of vegetables unconsumed. Less than half of the students
      met the national meal standards for vitamins A and C, or Fe. CONCLUSIONS: Few
      students' lunch consumption met previous or new, strengthened NSLP lunch
      standards. Due to the relatively low intake of vegetables, intakes of vitamins A
      and C were of particular concern. Effective behavioural interventions, combined
      with marketing, communications and behavioural economics, will likely be
      necessary to encourage increased vegetable intake to meet the new meal standards.

PMID- 23866828
TI  - Efficacy and safety of concentration-controlled everolimus with reduced-dose
      cyclosporine in Japanese de novo renal transplant patients: 12-month results.
AB  - BACKGROUND: No study to date has evaluated the efficacy and safety of everolimus
      with reduced-exposure cyclosporine in Japanese de-novo renal transplant (RTx)
      patients. METHODS: This 12-month, multicenter, open-label study randomized (1:1)
      122 Japanese de-novo RTx patients to either an everolimus regimen (1.5 mg/day
      starting dose (target trough: 3 to 8 ng/ml) + reduced-dose cyclosporine) or a
      mycophenolate mofetil (MMF) regimen (2 g/day + standard dose cyclosporine). All
      patients received basiliximab and corticosteroids. Key endpoints at month 12 were
      composite efficacy failure (treated biopsy-proven acute rejection, graft loss,
      death, or loss to follow-up) and renal function (estimated glomerular filtration
      rate; Modification of Diet in Renal Disease-4). RESULTS: Clear cyclosporine
      exposure reduction was achieved in the everolimus group throughout the study (52%
      reduction at month 12). Month 12 efficacy failure rates showed everolimus 1.5 mg
      to be non-inferior to MMF (11.5% vs. 11.5%). The median estimated glomerular
      filtration rate at month 12 was 58.00 ml/minute/1.73 m2 in the everolimus group
      versus 55.25 ml/minute/1.73 m2 in the MMF group (P = 0.063). Overall, the
      incidence of adverse events was comparable between the groups with some
      differences in line with the known safety profile of the treatments. The
      everolimus group had a higher incidence of wound healing events and edema,
      whereas a higher rate of cytomegalovirus infections was reported in the MMF
      group. CONCLUSIONS: This study confirmed the efficacy of everolimus 1.5 mg/day
      (target trough: 3 to 8 ng/ml) in Japanese RTx patients for preventing acute
      rejection, while allowing for substantial cyclosporine sparing. Renal function
      and safety findings were comparable with previous reports from other RTx
      populations. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00658320.

PMID- 23866829
TI  - Investigational treatment suspension and enhanced cell-mediated immunity at
      rebound followed by drug-free remission of simian AIDS.
AB  - BACKGROUND: HIV infection persists despite antiretroviral treatment (ART) and is
      reignited as soon as therapies are suspended. This vicious cycle is fueled by the
      persistence of viral reservoirs that are invulnerable to standard ART protocols,
      and thus therapeutic agents able to target these reservoirs are needed. One such
      agent, auranofin, has recently been shown to decrease the memory T-cell reservoir
      in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize
      with a fully suppressive ART protocol and induce a drug-free post-therapy
      containment of viremia. RESULTS: We administered buthionine sulfoximine (BSO), an
      inhibitor of glutathione synthesis currently in clinical trials for cancer, in
      combination with auranofin to chronically SIVmac251-infected macaques under
      highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was
      followed, after therapy suspension, by a significant decrease of viral RNA and
      DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy
      control of the infection was achieved in animals with pre-therapy viral loads
      ranging from values comparable to average human set points to levels largely
      higher. This control was dependent on the presence CD8+ cells and associated with
      enhanced levels of cell-mediated immune responses. CONCLUSIONS: The level of post
      therapy viral set point reduction achieved in this study is the largest reported
      so far in chronically SIVmac251-infected macaques and may represent a promising
      strategy to improve over the current "ART for life" plight.

PMID- 23866831
TI  - Associations between capsular serotype, multilocus sequence type, and macrolide
      resistance in Streptococcus agalactiae isolates from Japanese infants with
      invasive infections.
AB  - SUMMARY Streptococcus agalactiae (group B streptococcus; GBS) isolates (n = 150)
      from infants with invasive infections between 2006 and 2011 were analysed for
      capsular serotype, multilocus sequence type, and antibiotic susceptibility. In
      cases with late-onset disease (n = 115), primary meningitis was predominant
      (62.6%), but represented only 39.1% in cases with early-onset disease (n = 23).
      The most common serotype was III (58.7%), followed by Ia (21.3%) and Ib (12.7%).
      Sequence types (STs) of serotype III strains included ST17 (50.0%), ST19 (26.1%),
      ST335 (18.2%), ST27 (4.5%), and ST1 (1.1%). Predominant STs of serotypes Ia and
      Ib were ST23 (81.3%) and ST10 (84.2%), respectively. No penicillin-resistant
      strains were detected, but 22.0% of strains had mef(A/E), erm(A), or erm(B)
      genes, which mediate macrolide resistance. A new ST335, possessing an mef(A/E)
      gene belonging to clonal complex 19 gradually increased in frequency. Improved
      prevention of invasive GBS infections in infants requires timely identification,
      and ultimately vaccine development.

PMID- 23866830
TI  - Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against
      ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of
      glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti
      Helicobacter pylori activity.
AB  - BACKGROUND: Mitrella kentii (M. kentii) (Bl.) Miq, is a tree-climbing liana that
      belongs to the family Annonaceae. The plant is rich with isoquinoline alkaloids,
      terpenylated dihydrochalcones and benzoic acids and has been reported to possess
      anti-inflammatory activity. The purpose of this study is to assess the
      gastroprotective effects of desmosdumotin C (DES), a new isolated bioactive
      compound from M. kentii, on gastric ulcer models in rats. METHODS: DES was
      isolated from the bark of M. kentii. Experimental rats were orally pretreated
      with 5, 10 and 20 mg/kg of the isolated compound and were subsequently subjected
      to absolute ethanol-induced acute gastric ulcer. Gross evaluation, mucus content,
      gastric acidity and histological gastric lesions were assessed in vivo. The
      effects of DES on the anti-oxidant system, non-protein sulfhydryl (NP-SH)
      content, nitric oxide (NO)level, cyclooxygenase-2 (COX-2) enzyme activity, bcl-2
      associated X (Bax) protein expression and Helicabacter pylori (H pylori) were
      also investigated. RESULTS: DES pre-treatment at the administered doses
      significantly attenuated ethanol-induced gastric ulcer; this was observed by
      decreased gastric ulcer area, reduced or absence of edema and leucocytes
      infiltration compared to the ulcer control group. It was found that DES
      maintained glutathione (GSH) level, decreased malondialdehyde (MDA) level,
      increased NP-SH content and NO level and inhibited COX-2 activity. The compound
      up regulated heat shock protein-70 (HSP-70) and down regulated Bax protein
      expression in the ulcerated tissue. DES showed interesting anti-H pylori effects.
      The efficacy of DES was accomplished safely without any signs of toxicity.
      CONCLUSIONS: The current study reveals that DES demonstrated gastroprotective
      effects which could be attributed to its antioxidant effect, activation of HSP-70
      protein, intervention with COX-2 inflammatory pathway and potent anti H pylori
      effect.

PMID- 23866832
TI  - The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic
      osteoarthritis, Kashin-Beck disease.
AB  - BACKGROUND: The purpose of the study was to understand the function and
      expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis
      of articular cartilage of the Kashin-Beck disease (KBD). METHODS: The changes of
      ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and
      chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as
      treatments to prevent apoptosis in chondrocytes from KBD patients. RESULTS: It
      was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in
      KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and
      ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p
      ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more
      effective than p38 inhibitor in preventing chondrocyte apoptosis at equal
      concentrations of 10 MUM. CONCLUSION: These findings indicated the expression of
      p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in
      cartilage with KBD.

PMID- 23866833
TI  - Diet, iron biomarkers and oxidative stress in a representative sample of
      Mediterranean population.
AB  - BACKGROUND: The consumption pattern characterized by high consumption of
      vegetables, fruit, fish, olive oil and red wine has been associated with
      improvements in the total antioxidant capacity of individuals and reduced
      incidence of diseases related to oxidation. Also, high body iron levels may
      contribute to increase the oxidative stress by the generation of reactive oxygen
      species. The objective of this study is to analyze the relationship between
      antioxidant and pro-oxidant factors obtained from the diet and iron biomarkers on
      lipoprotein oxidation and total antioxidant capacity in a representative sample
      of the Mediterranean population. METHODS: Cross-sectional prospective study,
      carried out with 815 randomly selected subjects (425 women and 390 men). Dietary
      assessment (3-day food records), iron biomarkers (serum ferritin, serum iron and
      transferrin saturation), biochemical markers of lipoperoxidation (TBARS),
      antioxidant capacity (ORAC) and CRP (C-Reactive Protein) were determined.
      Multiple Linear Regression (MLR) models were applied to analyze the association
      between diet factors and iron biomarkers on TBARS and ORAC levels. RESULTS: We
      observed that lipoperoxidation measured by TBARS increased by age but no
      differences were observed by sex. Antioxidant capacity measured by ORAC is
      independent of age and sex. In general, increasing age, tobacco, heme iron intake
      from meat and fish and transferrin saturation were independently and positively
      associated with TBARS, while non-heme iron was negatively associated. Vegetables,
      vitamin C intake and serum ferritin were positively associated with ORAC, whereas
      saturated fatty acids and meat intake were negatively associated. CONCLUSIONS: In
      our general population, we observed that oxidative stress is related to aging,
      but antioxidant capacity is not. The highest intake of dietary non-heme iron,
      vegetables and vitamin C intake exerts a protective effect against oxidation
      while the highest intake of dietary heme iron from meat and fish and saturated
      fatty acids are associated with increased oxidative stress. High levels of
      circulating iron measured by transferrin saturation are associated with increased
      oxidative stress in women however its association with the higher levels of serum
      ferritin is controversial.

PMID- 23866834
TI  - Indigenous injury outcomes: life satisfaction among injured Maori in New Zealand
      three months after injury.
AB  - BACKGROUND: Maori, the indigenous population of New Zealand, experience numerous
      and consistent health disparities when compared to non-Maori. Injury is no
      exception, yet there is a paucity of published literature that examines outcomes
      following a wide variety of injury types and severities for this population. This
      paper aims to identify pre-injury and injury-related predictors of life
      satisfaction three months after injury for a group of injured Maori. METHODS: The
      Maori sample (n = 566) were all participants in the Prospective Outcomes of
      Injury Study (POIS). POIS is a longitudinal study of 2856 injured New Zealanders
      aged 18-64 years who were on an injury entitlement claims' register with New
      Zealand's no-fault compensation insurer. The well-known Te Whare Tapa Wha model
      of overall health and well-being was used to help inform the selection of post
      injury life satisfaction predictor variables. Multivariable analyses were used to
      examine the relationships between potential predictors and life satisfaction.
      RESULTS: Of the 566 Maori participants, post-injury life satisfaction data was
      available for 563 (99%) participants. Of these, 71% reported satisfaction with
      life three months after injury (compared to 93% pre-injury). Those with a higher
      injury severity score, not satisfied with pre-injury social relationships or poor
      self-efficacy pre-injury were less likely to be satisfied with life three months
      after injury. CONCLUSIONS: The large majority of Maori participants reported
      being satisfied with life three months after injury; however, nearly a third did
      not. This suggests that further research investigating outcomes after injury for
      Maori, and predictors of these, is necessary. Results show that healthcare
      providers could perhaps put greater effort into working alongside injured Maori
      who have more severe injuries, report poor self-efficacy and were not satisfied
      with their pre-injury social relationships to ensure increased likelihood of
      satisfaction with life soon after injury.

PMID- 23866835
TI  - 'Huang Qi Elixir' for proteinuria in patients with diabetic nephropathy: a study
      protocol for a randomized controlled pilot trial.
AB  - BACKGROUND: Diabetic nephropathy (DN) is the major complication of diabetes;
      proteinuria is the hall mark of DN. Currently, the treatment for proteinuria is
      mainly limited to angiotensin converting enzyme (ACE) inhibitors or angiotensin
      II receptor blockers (ARBs). According to Traditional Chinese Medicine (TCM)
      theory, Chinese medicinals 'securing essence and tonifying the kidney' may be
      appropriate for proteinuria. The most promising Chinese medicinals and formulae
      are introduced in the present study to form a potent formula for DN proteinuria.
      To make oral administration convenient, the formula will be processed in the form
      of granules. METHODS/DESIGN: A randomized, multi-center pilot trial will be
      conducted. Forty eight participants with DN will be randomly assigned to one of
      four treatment groups: 1. A granule group, at 10 grams, three times daily (G10
      group, n = 12); 2. A granule group, at 20 grams, three times daily (G20 group, n
      = 12); 3. A decoction group (D group, n = 12); and 4. An irbesartan group
      (Aprovel group, n = 12).The following outcome measures will be used: the
      percentage change of the albumin-to-creatinine ratio; and the changes in serum
      creatinine, glomerular filtration rate, fasting plasma glucose and hemoglobulin
      from baseline to the end of the trial. DISCUSSION: It is notable that most
      published clinical trials which assessed the efficacy of TCM on DN were of poor
      methodology and, therefore, their results have been invalidated. It is necessary
      to carry out well-designed clinical trials to provide sound evidence. The present
      trial is a study with potentially great value, for it will provide the parameters
      for future randomized, placebo-controlled, clinical trials with large sample
      sizes. TRIAL REGISTRATION: The trial is registered on the Chinese Clinical Trial
      Registry: ChiCTR-TRC-12002718
      (http://www.chictr.org/cn/proj/show.aspx?proj=3820).

PMID- 23866836
TI  - Three-dimensional systems for in vitro follicular culture: overview of alginate
      based matrices.
AB  - The in vitro culture of ovarian follicles has provided critical insight into the
      biology of the follicle and its enclosed oocyte and the physical interaction and
      communication between the theca and granulosa cells and the oocyte that is
      necessary to produce meiotically competent oocytes. Various two-dimensional (2D)
      and three-dimensional (3D) culture systems have been developed to evaluate the
      effect of growth factors, hormones, extracellular matrix components and culture
      conditions on follicle development and oocyte growth and maturation. Among these
      culture systems, 3D systems make it possible to maintain follicle structure and
      support communication between the various cell compartments within the follicle.
      In this review article, we will discuss the three main approaches to ovarian
      follicle culture: 2D attachment systems, 3D floating systems and 3D encapsulated
      systems. We will specifically emphasise the development of and advances in
      alginate-based encapsulated systems for in vitro follicle culture. 

PMID- 23866839
TI  - Voice rest after vocal fold surgery: current practice and evidence.
AB  - OBJECTIVE: Voice rest is commonly recommended after vocal fold surgery, but there
      is a lack of evidence base and no standard protocol. The aim of this study was to
      establish common practice regarding voice rest following vocal fold surgery.
      METHOD: An online survey was circulated via e-mail invitation to members of the
      ENT UK Expert Panel between October and November 2011. RESULTS: The survey
      revealed that 86.5 per cent of respondents agreed that 'complete voice rest'
      means no sound production at all, but there was variability in how 'relative
      voice rest' was defined. There was no dominant type of voice rest routinely
      recommended after surgery for laryngeal papillomatosis or intermediate
      pathologies. There was considerable variability in the duration of voice rest
      recommended, with no statistically significant, most popular response (except for
      malignant lesions). Surgeons with less than 10 years of experience were more
      likely to recommend fewer days of voice rest. CONCLUSION: There is a lack of
      consistency in advice given to patients after vocal fold surgery, in terms of
      both type and length of voice rest. This may arise from an absence of robust
      evidence on which to base practice.

PMID- 23866840
TI  - Coral aquaculture to support drug discovery.
AB  - Marine natural products (NP) are unanimously acknowledged as the 'blue gold' in
      the urgent quest for new pharmaceuticals. Although corals are among the marine
      organisms with the greatest diversity of secondary metabolites, growing evidence
      suggest that their symbiotic bacteria produce most of these bioactive
      metabolites. The ex hospite culture of coral symbiotic microbiota is extremely
      challenging and only limited examples of successful culture exist today. By
      contrast, in toto aquaculture of corals is a commonly applied technology to
      produce corals for aquaria. Here, we suggest that coral aquaculture could as well
      be a viable and economically feasible option to produce the biomass required to
      execute the first steps of the NP-based drug discovery pipeline. 

PMID- 23866841
TI  - Fertility preservation in female classic galactosemia patients.
AB  - Almost every female classic galactosemia patient develops primary ovarian
      insufficiency (POI) as a diet-independent complication of the disease. This is a
      major concern for patients and their parents, and physicians are often asked
      about possible options to preserve fertility. Unfortunately, there are no
      recommendations on fertility preservation in this group. The unique
      pathophysiology of classic galactosemia with a severely reduced follicle pool at
      an early age requires an adjusted approach. In this article recommendations for
      physicians based on current knowledge concerning galactosemia and fertility
      preservation are made. Fertility preservation is only likely to be successful in
      very young prepubertal patients. In this group, cryopreservation of ovarian
      tissue is currently the only available technique. However, this technique is not
      ready for clinical application, it is considered experimental and reduces the
      ovarian reserve. Fertility preservation at an early age also raises ethical
      questions that should be taken into account. In addition, spontaneous conception
      despite POI is well described in classic galactosemia. The uncertainty
      surrounding fertility preservation and the significant chance of spontaneous
      pregnancy warrant counseling towards conservative application of these
      techniques. We propose that fertility preservation should only be offered with
      appropriate institutional research ethics approval to classic galactosemia girls
      at a young prepubertal age. 

PMID- 23866843
TI  - Correlates of adiposity in a Caribbean pre-school population.
AB  - OBJECTIVE: To evaluate ethnic and anthropometric correlates of adiposity among a
      nationally representative, multi-ethnic, Trinidadian pre-school population.
      DESIGN: Cross-sectional study conducted between June 2008 and July 2009. SETTING:
      Government and privately owned Early Childhood Care and Education Centres in
      Trinidad. SUBJECTS: A total of 596 pre-school children (aged 31-73 months) from
      thirty-four schools had their weight, height, mid-upper arm circumference, waist
      circumference, biceps and triceps skinfold thicknesses measured by a registered
      dietitian using standard procedures. Percentage body fat was estimated using a
      foot-to-foot bioelectric impedance analyser (Tanita 531, Tokyo, Japan). Date of
      birth, religion and ethnicity were extracted from school records and pre
      schoolers' ethnicity was categorized as East Indian, African, Mixed (a
      combination of two or more ethnicities), Chinese or Caucasian. RESULTS:
      Anthropometric variables explained significantly more of the variance in
      adiposity among girls (67.4-88.1 %) than boys (24.4-39.2 %; P < 0.0 0 1). Pre
      schoolers of African descent were significantly taller, heavier and had higher
      abdominal fat and mid-upper arm circumference than their East Indian and Mixed
      counterparts (all P < 0.001). The overall prevalence of excess adiposity (>=25 %
      body fat) as determined by bioelectrical impedance was 14.6 %, while 2.9 % of the
      children were undernourished according to WHO weight-for-age criteria.
      Differences in anthropometry were non-existent between children attending
      government and private pre-schools. CONCLUSIONS: Gender, ethnicity and
      anthropometry all explained excess adiposity in these pre-schoolers. These
      findings highlight the need to elucidate the mechanisms that may be involved in
      explaining these differences, particularly those of ethnic origin.

PMID- 23866842
TI  - Biological function of Presenilin and its role in AD pathogenesis.
AB  - Presenilins (PSs) are the catalytic core of gamma-secretase complex. However, the
      mechanism of FAD-associated PS mutations in AD pathogenesis still remains
      elusive. Here we review the general biology and mechanism of gamma-secretase and
      focus on the catalytic components - presenilins and their biological functions
      and contributions to the AD pathogenesis. The functions of presenilins are
      divided into gamma-secretase dependent and gamma-secretase independent ones. The
      gamma-secretase dependent functions of presenilins are exemplified by the
      sequential cleavages in the processing of APP and Notch; the gamma-secretase
      independent functions of presenilins include stabilizing beta-catenin in Wnt
      signaling pathway, regulating calcium homeostasis and their interaction with
      synaptic transmission. 

PMID- 23866845
TI  - Pregnant women's knowledge of weight, weight gain, complications of obesity and
      weight management strategies in pregnancy.
AB  - BACKGROUND: Obesity is increasingly common in the obstetric population. Maternal
      obesity and excess gestational weight gain (GWG) are associated with increased
      perinatal risk. There is limited published data demonstrating the level of
      pregnant women's knowledge regarding these problems, their consequences and
      management strategies.We aimed to assess the level of knowledge of pregnant women
      regarding: (i) their own weight and body mass index (BMI) category, (ii)
      awareness of guidelines for GWG, (iii) concordance of women's own expectations
      with guidelines, (iv) knowledge of complications associated with excess GWG, and
      (v) knowledge of safe weight management strategies in pregnancy. METHODS: 364
      pregnant women from a single center university hospital antenatal clinic were
      interviewed by an obstetric registrar. The women in this convenience sample were
      asked to identify their weight category, their understanding of the complications
      of obesity and excessive GWG in pregnancy and safe and/or effective weight
      management strategies in pregnancy. RESULTS: Nearly half (47.8%) of the study
      population were overweight or obese. 74% of obese women underestimated their BMI
      category. 64% of obese women and 40% of overweight women overestimated their
      recommended GWG. Women's knowledge of the specific risks associated with excess
      GWG or maternal obesity was poor. Women also reported many incorrect beliefs
      about safe weight management in pregnancy. CONCLUSIONS: Many pregnant women have
      poor knowledge about obesity, GWG, their consequences and management strategies.
      Bridging this knowledge gap is an important step towards improving perinatal
      outcomes for all pregnant women, especially those who enter pregnancy overweight
      or obese.

PMID- 23866846
TI  - Viral load dynamics in adult patients with A(H1N1)pdm09 influenza.
AB  - SUMMARY The dynamics of influenza A viral load in respiratory samples collected
      from adult A(H1N1)pdm09 influenza patients were investigated. Three respiratory
      specimens were obtained every 2-4 days and clinical findings were recorded at the
      time each specimen was collected. A total of 105 serial specimens were collected
      from 35 patients. Viral clearance was more rapid in patients aged 15-29 years
      than patients aged 30-49 years (P < 0.01) or >= 50 years (P < 0.01). Hospitalized
      patients showed slow viral clearance compared to outpatients (P < 0.01).
      Resolution of cough and headache was correlated with viral load reduction in
      respiratory specimens. Viral shedding was found in 17 patients (48.6%) 5 days
      after symptom onset. Time to hospital visit after symptom onset was significantly
      correlated with prolonged viral shedding (odds ratio 9.0, 95% confidence interval
      1.56-51.87, P = 0.01). These findings will contribute to infection control
      aspects with respect to managing patients with influenza virus infections.

PMID- 23866844
TI  - Development of prophylactic vaccines against HIV-1.
AB  - The focus of most current HIV-1 vaccine development is on antibody-based
      approaches. This is because certain antibody responses correlated with protection
      from HIV-1 acquisition in the RV144 phase III trial, and because a series of
      potent and broad spectrum neutralizing antibodies have been isolated from
      infected individuals. Taken together, these two findings suggest ways forward to
      develop a neutralizing antibody-based vaccine. However, understanding of the
      correlates of protection from disease in HIV-1 and other infections strongly
      suggests that we should not ignore CTL-based research. Here we review recent
      progress in the field and highlight the challenges implicit in HIV-1 vaccine
      design and some potential solutions. 

PMID- 23866847
TI  - MiRNA-329 targeting E2F1 inhibits cell proliferation in glioma cells.
AB  - BACKGROUND: MicroRNAs have recently emerged as key regulators of cancers, miR-329
      located on 14q32.31 is one of down-regulated miRNAs in glioma, but the function
      and molecular mechanisms of miR-329 in determining the malignant phenotype of
      human glioma are elusive. This study therefore was conducted to investigate the
      role of miR-329 in biological behaviors of human glioma LN18 and T98G cell lines
      and its molecular mechanisms. METHODS: Nine patients with GBM were analyzed for
      the expression of miR-329 by quantitative RT-PCR. MiR-329 overexpression was
      established by transfecting miR-329 precursor into LN18 and T98G cells, and its
      effects on cell proliferation were studied using MTT assay, anchorage-independent
      growth ability assay, colony formation assays, Bromodeoxyuridine labeling and
      immunofluorescence.The effects of miR-329 on cell cycle were studied by flow
      cytometry. The target of miR-329 was determined by luciferase assays. The
      regulation of miR-329 on Akt pathway was determined by western blot. RESULTS: The
      E2F1 was identified as the target of miR-329. Overexpression of miR-329 blocked
      G1/S transition in LN18 and T98G cell lines, dramatically suppressed cell
      proliferation and the ability of colony formation. MiR-329 significantly
      decreased the phosphorylation levels of intracellular kinases Akt and expression
      of cyclin D1, but the expression of p21 was upregulated, cell growth was
      suppressed by inhibiting E2F1-mediated Akt pathway. CONCLUSIONS: MiR-329 may
      inhibit cell proliferation in human glioma cells through regulating E2F1-mediated
      suppression of Akt pathway.

PMID- 23866848
TI  - Operative diagnosis for revision total hip arthroplasty is associated with
      patient-reported outcomes (PROs).
AB  - BACKGROUND: Little is known about the impact of the reason for revision total hip
      arthroplasty (THA) on the outcomes following revision THA. In this study, our
      objective was to assess the association of operative diagnosis with patient
      reported outcomes (PROs) after revision THA. METHODS: We used prospectively
      collected data from the Mayo Clinic Total Joint Registry that collects pre- and
      post-operative pain and function outcomes using a validated Hip questionnaire, on
      all revision THAs from 1993-2005. We used logistic regression to assess the odds
      of moderate-severe index hip pain and moderate-severe limitation in activities of
      daily living (ADLs) 2- and 5-years after revision THA. We calculated odds ratios
      (OR) and 95% confidence intervals (CIs). RESULTS: For the 2- and 5-year cohorts,
      the operative diagnosis was loosening/wear/osteolysis in 73% and 75%;
      dislocation/bone or prosthesis fracture/instability or non-union in 17% and 15%;
      and failed prior arthroplasty with components removed/infection in 11% and 11%,
      respectively. In multivariable-adjusted analyses that included preoperative ADL
      limitations, compared to patients with loosening/wear/osteolysis, patients with
      dislocation/fracture/instability/non-union had OR of 2.2 (95% CI, 1.3-3.5; p =
      0.002) for overall moderate-severe ADL limitation and those with failed prior
      arthroplasty/infection had OR of 1.6 (95% CI, 1.0-2.8; p = 0.06). At 5-years, ORs
      were lower and differences were no longer significant. Moderate-severe pain did
      not differ significantly by diagnosis, at 2- or 5-years in multivariable adjusted
      analyses, with one exception, i.e. failed prior arthroplasty/infection had a
      trend towards significance with odds ratio of 1.9 (95% CI, 0.9-3.8; p = 0.07).
      CONCLUSIONS: Operative diagnosis is independently associated with ADL
      limitations, but not pain, at 2-years after revision THA. Patients should be
      informed of the risk of poorer short-term outcomes based on their diagnosis.

PMID- 23866849
TI  - Qualitative study about the ways teachers react to feedback from resident
      evaluations.
AB  - BACKGROUND: Currently, one of the main interventions that are widely expected to
      contribute to teachers' professional development is confronting teachers with
      feedback from resident evaluations of their teaching performance. Receiving
      feedback, however, is a double edged sword. Teachers see themselves confronted
      with information about themselves and are, at the same time, expected to be role
      models in the way they respond to feedback. Knowledge about the teachers'
      responses could be not only of benefit for their professional development, but
      also for supporting their role modeling. Therefore, research about professional
      development should include the way teachers respond to feedback. METHOD: We
      designed a qualitative study with semi-structured individual conversations about
      feedback reports, gained from resident evaluations. Two researchers carried out a
      systematic analysis using qualitative research software. The analysis focused on
      what happened in the conversations and structured the data in three main themes:
      conversation process, acceptance and coping strategies. RESULTS: The result
      section describes the conversation patterns and atmosphere. Teachers accepted
      their results calmly, stating that, although they recognised some points of
      interest, they could not meet with every standard. Most used coping strategies
      were explaining the results from their personal beliefs about good teaching and
      attributing poor results to external factors and good results to themselves.
      However, some teachers admitted that they had poor results because of the fact
      that they were not "sharp enough" in their resident group, implying that they did
      not do their best. CONCLUSIONS: Our study not only confirms that the effects of
      feedback depend first and foremost on the recipient but also enlightens the
      meaning and role of acceptance and being a role model. We think that the results
      justify the conclusion that teachers who are responsible for the day release
      programmes in the three departments tend to respond to the evaluation results
      just like human beings do and, at the time of the conversation, are initially not
      aware of the fact that they are role models in the way they respond to feedback.

PMID- 23866850
TI  - The benefits of psychosocial interventions for cancer patients undergoing
      radiotherapy.
AB  - BACKGROUND: Many patients with cancer experience depression and anxiety, and an
      associated decrease in quality of life (QOL) during radiation therapy (RT). The
      main objective of the study was to determine the benefits of psychosocial
      interventions for cancer patients who received RT. METHODS: Patients with cancer
      (n = 178) who agreed to participate in the study were randomized to the
      intervention arm (n = 89) or the control arm (n = 89). Patients in the
      intervention group received psychosocial care during RT, whereas the control
      group received RT only. The benefits of the intervention were evaluated using the
      Zung Self-rating Depression Scale (SDS) to measure depression, the Self-rating
      Anxiety Scale (SAS) to assess anxiety, and the European Organization for Research
      and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) to
      survey health-related QOL. The association between intervention and survival was
      also assessed. RESULTS: Patients randomly assigned to the intervention arm showed
      significant improvements on symptoms of depression (p < 0.05) and anxiety (p <
      0.05), health-related QOL (p < 0.05) (i.e. better global health status, and
      physical and emotional functioning, and less insomnia) when compared with
      controls. In the subset analysis, female patients, those that received high dose
      irradiation, and those that underwent adjuvant chemotherapy could benefit more
      from psychosocial intervention. There was no difference between the two groups in
      disease-free survival (DFS) (2-year DFS 79.8% in the intervention arm and 76.4%
      in the control arm; p = 0.527) and overall survival (OS) (2-year OS 83.1% in the
      intervention arm and 84.3% in the control arm; p = 0.925) CONCLUSIONS:
      Psychosocial intervention is a cost-effective approach that can improve a
      patient's mood and QOL both during and after RT. However, the intervention was
      not found to reduce the risk of cancer recurrence and death. TRIAL REGISTRATION:
      ChiCTR-TRC-12002438.

PMID- 23866852
TI  - A complicated case of Carney complex: fifth reoperative cardiac surgery for
      resection of recurrent cardiac myxoma.

PMID- 23866851
TI  - Brain imaging predictors and the international study to predict optimized
      treatment for depression: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Approximately 50% of patients with major depressive disorder (MDD) do
      not respond optimally to antidepressant treatments. Given this is a large
      proportion of the patient population, pretreatment tests that predict which
      patients will respond to which types of treatment could save time, money and
      patient burden. Brain imaging offers a means to identify treatment predictors
      that are grounded in the neurobiology of the treatment and the pathophysiology of
      MDD. METHODS/DESIGN: The international Study to Predict Optimized Treatment in
      Depression is a multi-center, parallel model, randomized clinical trial with an
      embedded imaging sub-study to identify such predictors. We focus on brain
      circuits implicated in major depressive disorder and its treatment. In the full
      trial, depressed participants are randomized to receive escitalopram, sertraline
      or venlafaxine-XR (open-label). They are assessed using standardized multiple
      clinical, cognitive-emotional behavioral, electroencephalographic and genetic
      measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed
      participants (18 to 65 years old) will enter the study, of whom a target of 10%
      will be recruited into the brain imaging sub-study (approximately 67 participants
      in each treatment arm) and 67 controls. The imaging sub-study is conducted at the
      University of Sydney and at Stanford University. Structural studies include high
      resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density
      scans. Functional studies include standardized functional magnetic resonance
      imaging (MRI) with three cognitive tasks (auditory oddball, a continuous
      performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and
      masked non-conscious emotion processing tasks). After eight weeks of treatment,
      the functional MRI is repeated with the above tasks. We will establish the
      methods in the first 30 patients. Then we will identify predictors in the first
      half (n=102), test the findings in the second half, and then extend the analyses
      to the total sample. TRIAL REGISTRATION: International Study to Predict Optimized
      Treatment--in Depression (iSPOT-D). ClinicalTrials.gov, NCT00693849.

PMID- 23866853
TI  - HIV pre-exposure prophylaxis and treatment as prevention: a review of awareness
      and acceptability among men who have sex with men in the Asia-Pacific region and
      the Americas.
AB  - This review assesses acceptability research for HIV pre-exposure prophylaxis
      (PrEP) and treatment as prevention (TasP) among men who have sex with men (MSM)
      in the Asia-Pacific region and the Americas, evaluating awareness and attitudes.
      There has been limited research on the acceptability of PrEP outside the United
      States and no research to date evaluating the acceptability of TasP since the
      findings of the HIV Prevention Trials Network 052 trial were released. Existing
      research suggests that PrEP is reasonably acceptable to MSM, but few men are
      likely to perceive the need for it. Studies of HIV treatment optimism suggest
      that MSM are likely to be sceptical of TasP. 

PMID- 23866854
TI  - Does the carotenoid-based colouration of Polymorphus minutus facilitate its
      trophic transmission to definitive hosts?
AB  - Freshwater gammarids infected with the acanthocephalan parasite Polymorphus
      minutus show behavioural alterations but also differ from uninfected individuals
      in their appearance because of the carotenoid-based colouration of the parasite
      visible through the cuticle. However, it's not clear whether this phenotypic
      alteration is an adaptation favouring parasite transmission to the definitive
      host. To test this hypothesis, we investigated the selective preference of
      mallard towards two prey types: uninfected gammarids on which we applied a dot of
      inconspicuous brown paint, and uninfected gammarids on which we applied a dot of
      bright orange paint to mimic the change in appearance due to P. minutus without
      changes in host behaviour. Mallards showed a significant preference for orange
      painted gammarids regardless of how gammarids were distributed (isolated or
      aggregated). This suggests that parasite's colouration may play a role in
      enhanced transmission to definitive avian hosts. The role of P. minutus'
      colouration in the conspicuousness of gammarids has however to be balanced by the
      extent to which mallards use visual cues to forage in the field. From the
      perspective of a multidimensional manipulation, this study suggests that the
      change in appearance may act synergistically with the changes in behaviour to
      promote transmission to waterbirds.

PMID- 23866856
TI  - Chromatin integrity of ram spermatozoa. Relationships to annual fluctuations of
      scrotal surface temperature and temperature-humidity index.
AB  - The objective of the present study was to explore the potential relationships of
      ovine sperm chromatin integrity, quantified using the sperm chromatin structure
      assay (SCSA), to the heat load of the scrotum and the discomfort felt by the
      animals because of fluctuations of microclimatic factors at different time
      periods before ejaculation. Ejaculates were collected once per week from five
      Chios rams and four East Friesian rams for 12 months and stored in liquid
      nitrogen. Frozen-thawed semen samples were analyzed using the SCSA, to determine
      the DNA fragmentation index (DFI) and the percentage of cells outside the main
      sperm population (%DFI) in each one of the samples. Scrotal surface temperature
      (SST) of each ram was measured using an infrared thermometer on a daily basis.
      Ambient air temperature and relative humidity were recorded at hourly intervals
      throughout the experimental period and temperature-humidity index (THI) was used
      to assess the discomfort felt by the rams. Mean values of SST (SST mean) and THI
      (THI mean) were computed for eight different time periods (up to 61 days)
      preceding each ejaculation day (Day 0). A linear mixed-effect model analysis was
      performed to describe the relation of SCSA parameters to collection month, SST
      mean, and THI mean of different time periods before ejaculation. The results of
      the statistical analysis revealed a relation of %DFI to the SST mean of the last
      12 days preceding ejaculation, namely the period that resembled the phase of
      epididymal maturation. On the contrary, the variation of DFI was most adequately
      described by the linear mixed-effect model applied for Days 54 to 48 before
      ejaculation, which resembled the phase of spermatogonial mitoses. The effect of
      collection month was significant for DFI and %DFI, with semen samples collected
      in September and February exhibiting the lowest DFI values; a less profound
      seasonal pattern was detected for %DFI. The effect of THI mean on DFI and %DFI
      was proven nonsignificant in regard to all time periods. In conclusion, a
      relation of SCSA parameters to SST mean of different periods before ejaculation
      was shown in the present study, implying an effect of scrotal microenvironment on
      intratesticular and epididymal sperm population. In contrast, we failed to detect
      any effect of microclimate-induced discomfort felt by the animals on the
      chromatin integrity of frozen-thawed ram spermatozoa.

PMID- 23866855
TI  - A synonymous change, p.Gly16Gly in MECP2 Exon 1, causes a cryptic splice event in
      a Rett syndrome patient.
AB  - BACKGROUND: Mutations in MECP2 are the main cause of Rett Syndrome. To date, no
      pathogenic synonymous MECP2 mutation has yet been identified. Here, we
      investigated a de novo synonymous variant c.48C>T (p.Gly16Gly) identified in a
      girl presenting with a typical RTT phenotype. METHODS: In silico analyses to
      predict the effects of sequence variation on mRNA splicing were employed,
      followed by sequencing and quantification of lymphocyte mRNAs from the subject
      for splice variants MECP2_E1 and MECP2_E2. RESULTS: Analysis of mRNA confirmed
      predictions that this synonymous mutation activates a splice-donor site at an
      early position in exon 1, leading to a deletion (r.[=, 48_63del]), codon
      frameshift and premature stop codon (p.Glu17Lysfs*16) for MECP2_E1. For MECP2_E2,
      the same premature splice site is used, but as this is located in the
      5'untranslated region, no effect on the amino acid sequence is predicted.
      Quantitative analysis that specifically measured this cryptic splice variant also
      revealed a significant decrease in the quantity of the correct MECP2_E1
      transcript, which indicates that this is the etiologically significant mutation
      in this patient. CONCLUSION: These findings suggest that synonymous variants of
      MECP2 as well as other known disease genes-and de novo variants in particular-
      should be re-evaluated for potential effects on splicing.

PMID- 23866857
TI  - Significant improvement of pig cloning efficiency by treatment with LBH589 after
      somatic cell nuclear transfer.
AB  - The low success rate of animal cloning by somatic cell nuclear transfer (SCNT)
      associates with epigenetic aberrancy, including the abnormal acetylation of
      histones. Altering the epigenetic status by histone deacetylase inhibitors
      (HDACi) enhances the developmental potential of SCNT embryos. In the current
      study, we examined the effects of LBH589 (panobinostat), a novel broad-spectrum
      HDACi, on the nuclear reprogramming and development of pig SCNT embryos in vitro.
      In experiment 1, we compared the in vitro developmental competence of nuclear
      transfer embryos treated with different concentrations of LBH589. Embryos treated
      with 50 nM LBH589 for 24 hours showed a significant increase in the rate of
      blastocyst formation compared with the control or embryos treated with 5 or 500
      nM LBH589 (32.4% vs. 11.8%, 12.1%, and 10.0%, respectively, P < 0.05). In
      experiment 2, we examined the in vitro developmental competence of nuclear
      transfer embryos treated with 50 nM LBH589 for various intervals after activation
      and 6-dimethylaminopurine. Embryos treated for 24 hours had higher rates of
      blastocyst formation than the other groups. In experiment 3, when the acetylation
      of H4K12 was examined in SCNT embryos treated for 6 hours with 50 nM LBH589 by
      immunohistochemistry, the staining intensities of these proteins in LBH589
      treated SCNT embryos were significantly higher than in the control. In experiment
      4, LBH589-treated nuclear transfer and control embryos were transferred into
      surrogate mothers, resulting in three (100%) and two (66.7%) pregnancies,
      respectively. In conclusion, LBH589 enhances the nuclear reprogramming and
      developmental potential of SCNT embryos by altering the epigenetic status and
      expression, and increasing blastocyst quality. 

PMID- 23866858
TI  - Diet quality in young adults and its association with food-related behaviours.
AB  - OBJECTIVE: To determine the diet quality of a group of young adults and explore
      its associations with two food-related behaviours (involvement in meal
      preparation and consumption of commercially prepared meals). DESIGN: Cross
      sectional study of young adults. Sample characteristics, food-related behaviours
      and dietary intake were assessed using a self-administered questionnaire
      including an FFQ. Diet quality was measured using the fifteen-item Dietary
      Guideline Index (DGI) designed to assess adherence to Australian dietary
      guidelines. One-way ANOVA, t tests and multiple linear regression analyses were
      used to explore the relationships between DGI scores, sample characteristics and
      food-related behaviours. SETTING: University students enrolled in an
      undergraduate nutrition class, Melbourne, Australia. SUBJECTS: Students (n 309)
      aged 18-36 years. RESULTS: The DGI score was normally distributed, with a mean
      score of 93.4 (sd 17.1) points (range 51.9-127.4 points), out of a possible score
      of 150 points. In multivariate analyses adjusted for age, sex, nationality, BMI
      and maternal education, cooking meals for oneself was positively associated with
      DGI score (beta = 0.15; 95 % CI 1.15, 10.03; P = 0.01); frequency of takeaway and
      frequency of convenience meal consumption were inversely associated with DGI
      score (beta = -0.21; 95 % CI -9.96, -2.32; P = 0.002 and beta = -0.16; 95 % CI 
      7.40, -0.97; P < 0.01, respectively). CONCLUSIONS: Cooking meals for oneself was
      linked to higher diet quality among young adults, while consumption of
      commercially prepared meals was associated with poorer diet quality. Maintaining
      education programmes that promote cooking skills within young adults has the
      potential to improve DGI scores.

PMID- 23866859
TI  - Disability and health-related quality of life in patients undergoing spinal
      fusion: a comparison with a general population sample.
AB  - BACKGROUND: The aim of the present study was to compare one-year-follow-up data
      on disability and health-related quality of life (HRQoL) between spinal fusion
      patients and age- and sex-matched general population. METHODS: The data on fusion
      patients were collected prospectively using a spinal fusion data base in two
      Finnish hospitals. A general population sample matched for age, sex and
      residential area was drawn from the Finnish Population Register. All participants
      completed a questionnaire and the main outcome measures were the Oswestry
      Disability Index (ODI) and the Short Form-36 questionnaire (SF-36). RESULTS:
      Altogether 252 (69% females) fusion patients and 682 (67% females) population
      sample subjects participated in the study. In general population the mean ODI was
      15 (SD 17) in females and 9 (SD 13) in males. The corresponding preoperative ODI
      values were 47 (SD16) and 40 (SD 15) and one year follow-up values 22 (SD 17) and
      23 (SD 20). In both sexes the ODI decreased significantly after surgery but
      remained higher than in the general population, p < 0.001. The physical component
      summary score (PCS) of the SF-36 was lower in the patients than general
      population sample both preoperatively and at one-year follow-up (p < 0.001). The
      mental component summary score (MCS) was lower preoperatively (p < 0.001), but
      reached the general population level after one year in both men (p = 0.42) and
      women (p = 0.61). CONCLUSIONS: Disability and HRQoL improved significantly after
      spinal fusion surgery during a one- year follow-up. However, the patients did not
      reach the level of the general population in the ODI or in the physical component
      of HRQoL at that time, although in the mental component the difference
      disappeared.

PMID- 23866860
TI  - Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its
      stability and its anti-HIV-1 activity.
AB  - BACKGROUND: Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that
      methylates arginine residues on histones and transcription factors. In addition,
      PRMT6 inhibits HIV-1 replication in cell culture by directly methylating and
      interfering with the functions of several HIV-1 proteins, i.e. Tat, Rev and
      nucleocapsid (NC). PRMT6 also displays automethylation capacity but the role of
      this post-translational modification in its antiretroviral activity remains
      unknown. RESULTS: Here we report the identification by liquid chromatography-mass
      spectrometry of R35 within PRMT6 as the target residue for automethylation and
      have confirmed this by site-directed mutagenesis and in vitro and in vivo
      methylation assays. We further show that automethylation at position 35 greatly
      affects PRMT6 stability and is indispensable for its antiretroviral activity, as
      demonstrated in HIV-1 single-cycle TZM-bl infectivity assays. CONCLUSION: These
      results show that PRMT6 automethylation plays a role in the stability of this
      protein and that this event is indispensible for its anti-HIV-1 activity.

PMID- 23866861
TI  - Coronary calcium scoring: are the results comparable to computed tomography
      coronary angiography for screening coronary artery disease in a South Asian
      population?
AB  - BACKGROUND: The need of having feasible screening tools like Coronary Calcium
      Scoring (CCS) and CT Coronary Artery (CTCA) for Coronary Artery Disease (CAD) has
      become paramount. We aimed to evaluate the accuracy of CCS in determining the
      degree of stenosis of coronary vessels as compared to that determined by CTCA in
      a South Asian population. METHODS: A retrospective study was conducted at The Aga
      Khan University Hospital. A total of 539 patient records were reviewed who had
      undergone CCS and CTCA between 2008 and 2010. Patient records were reviewed by
      comparing their CCS and CTCA results. RESULTS: About 268 out of 301 (89%)
      patients with a CCS of 0-9 were found to be free of stenosis on CTCA. On a CCS of
      10-99, 110 out of 121 (91%) patients were either free of stenosis or had mild
      stenosis. About 66 out of 79 (84%) patients had moderate or severe stenosis with
      a calcium score of 100-400 while none of the patients were free of stenosis.
      Around 28 out of 38 (74%) patients with a CCS of more than 400 had severe
      stenosis. However, only 04 patients (11%) were found to have mild stenosis.
      Spearman's rho revealed a correlation coefficient of 0.791 with a p-value of
      <0.001. CONCLUSION: Our study reaffirms that in South Asian population, low CCS
      (<100) is associated with no or minimal stenosis while high CCS warrants further
      investigation; hence, making it a reliable tool for screening patients with CAD.

PMID- 23866862
TI  - "You'd know if you 'friended' me on Facebook": legal, moral, and ethical
      considerations of online social media.

PMID- 23866863
TI  - Cyclosporine as maintenance therapy in patients with severe psoriasis.

PMID- 23866864
TI  - Treatment of mucous membrane pemphigoid with rituximab.

PMID- 23866865
TI  - Reply to "Treatment of mucous membrane pemphigoid with rituximab".

PMID- 23866866
TI  - Antinuclear antibodies do not predict anti-infliximab antibody induction in
      sarcoidosis.

PMID- 23866867
TI  - Comment on "Specialty bashing during medical training: experiences of students
      applying to a dermatology residency program".

PMID- 23866868
TI  - The significance of the development of antinuclear antibodies during infliximab
      treatment.

PMID- 23866869
TI  - Respect begins at home.

PMID- 23866870
TI  - Dermatopsychopharmacology.

PMID- 23866871
TI  - Comment on 2012 appropriate use criteria for Mohs micrographic surgery.

PMID- 23866872
TI  - Reply to "Comment on 2012 appropriate use criteria for Mohs micrographic
      surgery".

PMID- 23866873
TI  - Combination of intravenous immunoglobulins and lenalidomide in the treatment of
      scleromyxedema.

PMID- 23866874
TI  - Topical amitriptyline combined with topical ketamine for the management of
      recalcitrant localized pruritus: a retrospective pilot study.

PMID- 23866875
TI  - JAAD Grand Rounds. Multiple papules on the nose.

PMID- 23866876
TI  - JAAD Grand Rounds. Stellate-shaped ulcers and violaceous plaques.

PMID- 23866877
TI  - JAAD Grand Rounds. Acral erythematous papules and dysmorphic features.

PMID- 23866878
TI  - Toxic epidermal necrolysis: Part I. Introduction, history, classification,
      clinical features, systemic manifestations, etiology, and immunopathogenesis.
AB  - Toxic epidermal necrolysis is a life-threatening, typically drug-induced
      mucocutaneous disease. It is clinically characterized as a widespread sloughing
      of the skin and mucosa, including both external and internal surfaces.
      Histologically, the denuded areas show full thickness epidermal necrosis. The
      pathogenic mechanism involves antigenic moiety/metabolite, peptide-induced T cell
      activation, leading to keratinocyte apoptosis through soluble Fas ligand,
      perforin/granzyme B, tumor necrosis factor-alfa, and nitric oxide. Recent studies
      have implicated granulysin in toxic epidermal necrolysis apoptosis and have
      suggested that it may be the pivotal mediator of keratinocyte death. 

PMID- 23866879
TI  - Toxic epidermal necrolysis: Part II. Prognosis, sequelae, diagnosis, differential
      diagnosis, prevention, and treatment.
AB  - Toxic epidermal necrolysis (TEN) is a life-threatening, typically drug-induced,
      mucocutaneous disease. TEN has a high mortality rate, making early diagnosis and
      treatment of paramount importance. New but experimental diagnostic tools that
      measure serum granulysin and high-mobility group protein B1 (HMGB1) offer the
      potential to differentiate early TEN from other, less serious drug reactions, but
      these tests have not been validated and are not readily available. The mainstay
      of treatment for TEN involves discontinuation of the offending drug, specialized
      care in an intensive care unit or burn center, and supportive therapy.
      Pharmacogenetic studies have clearly established a link between human leukocyte
      antigen allotype and TEN. Human leukocyte antigen testing should be performed on
      patients of East Asian descent before the initiation of carbamezapine and on all
      patients before the initiation of abacavir. The effectiveness of systemic
      steroids, intravenous immunoglobulins, plasmapheresis, cyclosporine, biologics,
      and other agents is uncertain. 

PMID- 23866880
TI  - Elafin: a possible new biomarker and immunohistochemical stain for pre
      engraftment syndrome.

PMID- 23866881
TI  - Erythema papulatum centrifugum: a sweat-related dermatitis.

PMID- 23866882
TI  - Successful treatment of atypical adult pityriasis rubra pilaris with oral
      alitretinoin.

PMID- 23866883
TI  - Buprenorphine-induced linear IgA bullous dermatosis "down the rail".

PMID- 23866884
TI  - Autologous fat transfer-induced facial nodule.

PMID- 23866887
TI  - Clonal seborrheic keratosis versus epidermal nevus.

PMID- 23866888
TI  - An evidence-based checklist for melanoma patient triage.

PMID- 23866889
TI  - Safe and speedy cantharidin application.

PMID- 23866890
TI  - How to prepare patients for ablative laser procedures.

PMID- 23866891
TI  - Physician survey of dermatology quality reporting initiatives in Colorado.

PMID- 23866892
TI  - Mobile teledermatology in Ghana: sending and answering consults via mobile
      platform.

PMID- 23866893
TI  - Vaginal adenosis as a dermatologic complaint.

PMID- 23866894
TI  - Pseudomonas folliculitis contracted from rubber gloves: a public health concern.

PMID- 23866895
TI  - A plastic ear bonnet to protect postsurgical ear wounds.

PMID- 23866896
TI  - Vemurafenib (PLX-4032)-induced keratoses: verrucous but not verrucae.

PMID- 23866897
TI  - Topical bexarotene for psoralen plus ultraviolet A-induced photodamage.

PMID- 23866898
TI  - Composite hemangioendothelioma presenting as a scalp nodule with alopecia.

PMID- 23866899
TI  - Effective treatment of idiopathic chronic cold urticaria with omalizumab: report
      of 3 cases.

PMID- 23866900
TI  - Functional maturation of nasal mucosa: role of secretory immunoglobulin A (SIgA).
AB  - Secretory IgA (SIgA) plays an important role in defending the mucous membranes of
      the upper respiratory airways from common infection. Studying and comparing the
      values and the daily variation of SIgA in nasal secretion could explain the
      largest number of upper respiratory infection, especially in children.Moreover,
      the ELISA dosage of SIgA in nasal secretion, sampled by cotton swabs positioned
      between septum and middle turbinate for 20 minutes every 4 hours 5 times in a
      day, can be easily performed and shows significant differences between the
      healthy child and the healthy adult.Nasal secretion SIgA mean value is lower in
      the healthy child than in the healthy adult. Circadian variation for healthy
      child showed the highest value at 7.00 a.m., while in adult the highest value was
      at 4.00 a.m.These knowledge on SIgA may help to explain the highest number of
      upper airway infection during childhood and clarify the physiological cycle of
      production. Thus, in performing a SIgA dosage the time of sample must be
      considered and preferably it should be made at a standardized time of the day. 

PMID- 23866901
TI  - A re-examination of neural basis of language processing: proposal of a dynamic
      hodotopical model from data provided by brain stimulation mapping during picture
      naming.
AB  - From recent findings provided by brain stimulation mapping during picture naming,
      we re-examine the neural basis of language. We studied structural-functional
      relationships by correlating the types of language disturbances generated by
      stimulation in awake patients, mimicking a transient virtual lesion both at
      cortical and subcortical levels (white matter and deep grey nuclei), with the
      anatomical location of the stimulation probe. We propose a hodotopical
      (delocalized) and dynamic model of language processing, which challenges the
      traditional modular and serial view. According to this model, following the
      visual input, the language network is organized in parallel, segregated (even if
      interconnected) large-scale cortico-subcortical sub-networks underlying semantic,
      phonological and syntactic processing. Our model offers several advantages (i) it
      explains double dissociations during stimulation (comprehension versus naming
      disorders, semantic versus phonemic paraphasias, syntactic versus naming
      disturbances, plurimodal judgment versus naming disorders); (ii) it takes into
      account the cortical and subcortical anatomic constraints; (iii) it explains the
      possible recovery of aphasia following a lesion within the "classical" language
      areas; (iv) it establishes links with a model executive functions. 

PMID- 23866902
TI  - Educating on professional habits: attitudes of medical students towards diverse
      strategies for promoting influenza vaccination and factors associated with the
      intention to get vaccinated.
AB  - BACKGROUND: Influenza vaccination coverage in medical students is usually low.
      Unlike health care workers, there is little information on the attitudes to and
      predictors of vaccination among medical students, and their attitudes towards
      institutional strategies for improving rates are unknown. METHODS: This cross
      sectional study evaluated the effect of three influenza vaccination promotional
      strategies (Web page, video and tri-fold brochure) on medical students' intention
      to get vaccinated and associated factors. A total of 538 medical students were
      asked to answer an anonymous questionnaire assessing the intention to get
      vaccinated after exposure to any of the promotional strategies. Sociodemographic
      data collected included: sex, age, university year, influenza risk group and
      cohabiting with member of a risk group. RESULTS: Four hundred twenty-one students
      answered the questionnaire, of whom 312 (74.1%) were female, 113 (26.8%) had done
      clinical rotations, and 111 (26.6%) reported intention to get the flu shot.
      Logistic regression showed the web group had a greater intention to get
      vaccinated than the reference group (OR: 2.42 95% CI: 1.16-5.03). Having done
      clinical rotations (OR: 2.55 95% CI: 1.36-4.38) and having received the shot in
      previous flu seasons (OR: 13.69 95% CI: 7.86-23.96) were independently associated
      with the intention to get vaccinated. CONCLUSION: Given that previous vaccination
      is a factor associated with the intention to get vaccinated, education on
      vaccination of health care workers should begin while they are students, thereby
      potentiating the habit. In addition, the intention to get vaccinated was greater
      during the clinical phase of the university career, suggesting this is a good
      time to introduce promotion strategies. Online promotional campaigns, such as a
      thematic Web to promote vaccination of health workers, could improve the
      intention to get vaccinated.

PMID- 23866903
TI  - EMG-based facial gesture recognition through versatile elliptic basis function
      neural network.
AB  - BACKGROUND: Recently, the recognition of different facial gestures using facial
      neuromuscular activities has been proposed for human machine interfacing
      applications. Facial electromyograms (EMGs) analysis is a complicated field in
      biomedical signal processing where accuracy and low computational cost are
      significant concerns. In this paper, a very fast versatile elliptic basis
      function neural network (VEBFNN) was proposed to classify different facial
      gestures. The effectiveness of different facial EMG time-domain features was also
      explored to introduce the most discriminating. METHODS: In this study, EMGs of
      ten facial gestures were recorded from ten subjects using three pairs of surface
      electrodes in a bi-polar configuration. The signals were filtered and segmented
      into distinct portions prior to feature extraction. Ten different time-domain
      features, namely, Integrated EMG, Mean Absolute Value, Mean Absolute Value Slope,
      Maximum Peak Value, Root Mean Square, Simple Square Integral, Variance, Mean
      Value, Wave Length, and Sign Slope Changes were extracted from the EMGs. The
      statistical relationships between these features were investigated by Mutual
      Information measure. Then, the feature combinations including two to ten single
      features were formed based on the feature rankings appointed by Minimum
      Redundancy-Maximum-Relevance (MRMR) and Recognition Accuracy (RA) criteria. In
      the last step, VEBFNN was employed to classify the facial gestures. The
      effectiveness of single features as well as the feature sets on the system
      performance was examined by considering the two major metrics, recognition
      accuracy and training time. Finally, the proposed classifier was assessed and
      compared with conventional methods support vector machines and multilayer
      perceptron neural network. RESULTS: The average classification results showed
      that the best performance for recognizing facial gestures among all single/multi
      features was achieved by Maximum Peak Value with 87.1% accuracy. Moreover, the
      results proved a very fast procedure since the training time during
      classification via VEBFNN was 0.105 seconds. It was also indicated that MRMR was
      not a proper criterion to be used for making more effective feature sets in
      comparison with RA. CONCLUSIONS: This work was accomplished by introducing the
      most discriminating facial EMG time-domain feature for the recognition of
      different facial gestures; and suggesting VEBFNN as a promising method in EMG
      based facial gesture classification to be used for designing interfaces in human
      machine interaction systems.

PMID- 23866904
TI  - Hydrogen treatment-improved uniform deposition of Ag nanoparticles on ZnO nanorod
      arrays and their visible-light photocatalytic and surface-enhanced Raman
      scattering properties.
AB  - ZnO nanorod arrays were synthesized by chemical bath deposition. After heat
      treatment in hydrogen or air, Ag nanoparticles were deposited on ZnO nanorod
      arrays by photo-reduction method. The size of Ag nanoparticles as well as the
      surface morphology, structure, composition, and optical property of ZnO nanorod
      arrays before and after the deposition of Ag nanoparticles were characterized by
      SEM, XRD, EDS, and UV/VIS/NIR spectrophotometer. As compared to the samples with
      heat treatment in air or without heat treatment, the ZnO nanorod arrays after
      heat treatment in hydrogen allowed Ag nanoparticles to be deposited more
      uniformly, densely, and numerously. Also, they exhibited higher efficiency for
      the visible light-driven photocatalytic degradation of Rhodamine 6G (R6G) dye.
      The effects of the amount of Ag nanoparticles, initial dye concentration, and
      temperature on the photocatalytic degradation efficiency were investigated.
      Furthermore, they also exhibited better surface-enhanced Raman scattering
      property for the detection of R6G dyes. 

PMID- 23866905
TI  - The impact of podoconiosis on quality of life in Northern Ethiopia.
AB  - BACKGROUND: Podoconiosis is one of the most neglected tropical diseases, which
      untreated, causes considerable physical disability and stigma for affected
      individuals. Little is known about the quality of life (QoL) of patients with
      podoconiosis. This study aimed to assess the QoL of patients with podoconiosis in
      comparison with healthy controls in Ethiopia. METHODS: A comparative cross
      sectional study was conducted in May 2012, among 346 clinically confirmed adult
      patients with podoconiosis, and 349 healthy adult neighbourhood controls in
      Dembecha woreda (district) in northern Ethiopia. QoL was assessed using the
      validated Amharic version of the World Health Organisation Quality of Life
      questionnaire (WHOQoL-BREF) scale; in addition, mental health and stigma were
      assessed by the Kessler-10 scale and podoconiosis stigma scale respectively.
      Logistic regression analysis was done to identify factors associated with QoL.
      RESULTS: Patients with podoconiosis had significantly lower mean overall QoL than
      the controls (52.05 versus 64.39), and this was also true in all four sub domains
      (physical, psychological, social and environmental). Controls were 7 times more
      likely to have high (above median) QoL (Odds Ratio = 6.74, 95% Confidence
      Interval 4.62 to 9.84) than cases. Factors associated with lower QoL were:
      experiencing high levels of stigma, living in an urban area, being illiterate,
      having additional co-morbidities, and being unmarried. Mental illness was
      associated with lower scores in psychological and physical domains. CONCLUSIONS:
      Programs targeting podoconiosis interventions should include QoL as an indicator
      for monitoring progress. Interventions targeting improvement of QoL among
      patients with podoconiosis should address depression, stigma and other co
      morbidities.

PMID- 23866907
TI  - Genetic testing of sperm donors for cystic fibrosis and spinal muscular atrophy:
      evaluation of clinical utility.
AB  - OBJECTIVE: To evaluate the clinical utility of genetic testing for cystic
      fibrosis (CF) and spinal muscular atrophy (SMA) in sperm donors. STUDY DESIGN: We
      studied the results of the genetic tests for CF and SMA applied to 372 sperm
      donor candidates. The CF carrier screening test analysed 32 mutations on the CFTR
      gene. Regarding SMA, the carrier test studied possible deletions of SMN1/2 by
      Multiplex Ligation-dependent Probe Amplification (MLPA) methodology. RESULTS: The
      carrier frequency obtained was greater for SMA than for CF. After adjusting the
      results obtained for the sensitivity of the tests, and taking into account the
      prevalence of female carriers in our population, the probability of transmission
      of the disease to the child from a donor with a negative genetic test was about
      five times lower in the case of SMA than in CF, although this difference was not
      statistically significant. The number of donors needed to screen (NNS) to avoid
      the occurrence of a child being affected by CF and SMA in our population was
      similar in both cases (1591 vs. 1536). CONCLUSIONS: This study demonstrates the
      need to include SMA among the diseases for which genetic screening is performed
      in the process of sperm donor selection. We believe that testing donors for SMA
      is as important and as useful as doing so for CF.

PMID- 23866906
TI  - Electroacupuncture to treat painful diabetic neuropathy: study protocol for a
      three-armed, randomized, controlled pilot trial.
AB  - BACKGROUND: The purpose of this study is to conduct a basic analysis of the
      effectiveness and safety of electroacupuncture in the treatment of painful
      diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate
      the feasibility of large-scale clinical research. METHODS/DESIGN: This study is a
      protocol for a three-armed, randomized, patient-assessor-blinded (to the type of
      treatment), controlled pilot trial. Forty-five participants with a >= six month
      history of PDN and a mean weekly pain score of >= 4 on the 11-point Pain
      Intensity Numerical Rating Scale (PI-NRS) will be assigned to the
      electroacupuncture group (n = 15), sham group (n = 15) or usual care group (n =
      15). The participants assigned to the electroacupuncture group will receive
      electroacupuncture (remaining for 30 minutes with a mixed current of 2 Hz/120 Hz
      and 80% of the bearable intensity) at 12 standard acupuncture points (bilateral
      ST36, GB39, SP9, SP6, LR3 and GB41) twice per week for eight weeks (a total of 16
      sessions) as well as the usual care. The participants in the sham group will
      receive sham electroacupuncture (no electrical current will be passed to the
      needle, but the light will be seen, and the sound of the pulse generator will be
      heard by the participants) at non-acupuncture points as well as the usual care.
      The participants in the usual care group will not receive electroacupuncture
      treatment during the study period and will receive only the usual care. The
      follow-up will be in the 5th, 9th and 17th weeks after random allocation. The PI
      NRS score assessed at the ninth week will be the primary outcome measurement used
      in this study. The Short-Form McGill Pain Questionnaire (SF-MPQ), a sleep
      disturbance score (11-point Likert scale), the Short-Form 36v2 Health Survey (SF
      36), the Beck Depression Inventory (BDI) and the Patient Global Impression of
      Change (PGIC) will be used as outcome variables to evaluate the effectiveness of
      the acupuncture. Safety will be assessed at every visit. DISCUSSION: The result
      of this trial will provide a basis for the effectiveness and safety of
      electroacupuncture for PDN. TRIAL REGISTRATION: Clinical Research information
      Service. Unique identifier: KCT0000466.

PMID- 23866908
TI  - The occurrence of endometriosis with ovarian carcinomas is not purely
      coincidental.
AB  - OBJECTIVE: To explore the association between epithelial ovarian cancer (EOC) and
      common benign gynecological disorders. STUDY DESIGN: The medical records of 226
      patients with EOC treated at Peking Union Medical College Hospital between March
      2011 and March 2012 were reviewed. Histological evaluations had been performed to
      determine the presence of coexisting pelvic endometriosis (n=17), uterine
      leiomyoma (n=66), adenomyosis (n=22), or endometrial polyps (n=17). RESULTS:
      Coexistence of endometriosis occurred in 35.3% and 36.4% of cases of the clear
      cell and endometrioid subtypes of EOC histology, respectively. Endometriosis was
      more likely associated with clear cell or endometrioid ovarian carcinoma, but
      less likely with high grade serous cancer. No differences were observed in the
      concurrence of uterine myoma, adenomyosis or endometrial polyps among the
      different subtypes of EOC. CONCLUSIONS: In contrast to other common benign
      gynecological disorders, endometriosis showed close relationships with the clear
      cell and endometrioid subtypes of EOC specifically.

PMID- 23866909
TI  - Regular exercise is the most significant lifestyle parameter associated with the
      severity of climacteric symptoms: a cross sectional study.
AB  - OBJECTIVE: To assess the association between demographic and lifestyle parameters
      and perceived severity of the climacteric syndrome in perimenopausal women. STUDY
      DESIGN: A cross-sectional study of 151 healthy women aged 45-55 years who
      attended the University Medical Center affiliated menopause clinics. The analysis
      was based on self completion of the Greene climacteric score, consisting of
      psychological, somatic/physical, sexual and vasomotor subscores. The Greene total
      score and subscores were the main outcomes of the study. RESULTS: Of all
      demographic, anthropometric and lifestyle parameters recorded, the correlates
      with reduced total Greene score were high-order maternity and regular physical
      exercise. Mothers of 3 or more children reported significantly lower total Greene
      score (18+/-12.8 vs. 22.1+/-8.1) (p=0.01) as well as lower psychological subscore
      (8.7+/-6.8 vs. 11.5+/-5.4) (p=0.01). Regular physical activity was also
      associated with significantly lower total Greene score (17.0+/-11.0 vs. 22.6+/
      11.3) (p=0.01) and specifically lower psychological subscore (9.5+/-6.6 vs.
      12.8+/-7.7) (p=0.03) and sexual subscore (1.1+/-0.99 vs. 1.61+/-1.05) (p=0.03).
      Linear regression models showed that regular exercise was the lifestyle parameter
      most significantly correlated with a lower total Greene score (p=0.006)
      independent of menopausal status. Of particular note, regular exercise was
      significantly correlated with lower psychological (p=0.006) and physical
      subscores (p=0.06). Moreover, the higher the frequency of exercise (both aerobic
      and non aerobic), the lower the severity of the climacteric symptoms reported,
      yet the vasomotor and sexual subscores remained unchanged. CONCLUSIONS: Regular
      exercise of at least 3 times a week was the most significant lifestyle parameter
      to be associated with the severity of climacteric symptoms.

PMID- 23866911
TI  - Method validation for norovirus detection in naturally contaminated irrigation
      water and fresh produce.
AB  - Human enteric viruses are shed in extremely high numbers in the feces of infected
      individuals, becoming environmental contaminants and eventually leading to
      contamination of a variety of foodstuffs at the pre-harvest stage. Among these
      foods at risk is fresh produce and irrigation water is a major vehicle for crop
      contamination. In the present study, a standardized molecular method for
      quantitative virus assay has been evaluated in different types of fresh produce
      and in irrigation water for human norovirus (NoV) detection. Two different virus
      concentration procedures, polyethylene-glycol precipitation (PEG) and organic
      flocculation (OF), were employed. The procedures were initially assayed in spiked
      samples and later validated on naturally contaminated samples from the Nile Delta
      in Egypt. Overall, PEG provided significantly (p<0.05) better virus recoveries
      than OF for both irrigation water and salad vegetable virus analysis. NoV GI and
      GII recoveries in spiked irrigation water ranged from 22.0% to 43.3% and from
      12.6% to 16.4% with the PEG and OF methods, respectively. In experimentally
      contaminated salad vegetables, virus recoveries ranged from 28.0% to 48.0% and
      from 14.0% to 18.8% by PEG precipitation and OF, respectively. Using PEG
      precipitation, NoV was found in 31.9% of naturally contaminated irrigation water
      samples. Both NoV GI and GII were detected in these samples with genome copy
      numbers of around 10(2) per liter. Virus analyses performed in naturally
      contaminated fresh produce that included green onion, watercress, radish, leek,
      and lettuce show that NoV GI was present in 20.8%-34.0% of the samples with
      genome copy numbers of around 10(2) per gram. When OF was employed, NoV was found
      in 25.0% of the irrigation water samples. Both genogroups could be found in these
      samples with genome copy numbers of around 10 per liter. In fresh produce, GI was
      present in 16.0%-25.7% of the samples with genome copy numbers per gram of around
      10. Surprisingly, NoV GII was not detected in any salad vegetable despite highly
      satisfactory virus/nucleic acid extraction and enzyme efficiencies reported in
      the assays. Available reliable standardized assays for virus detection in food
      matrices including appropriate quality assurance and quality control measures to
      assess the efficiency of critical steps in virus analysis open the possibility to
      produce consistent and accurate exposure data to be used in QMRA (quantitative
      microbial risk assessment) and at the same time may enable the formulation of
      guidelines to ensure the virological quality of selected commodities in specific
      scenarios to reduce the risk of foodborne virus infections. 

PMID- 23866910
TI  - Influencing cocoa flavour using Pichia kluyveri and Kluyveromyces marxianus in a
      defined mixed starter culture for cocoa fermentation.
AB  - The potential impact of aromatic and pectinolytic yeasts on cocoa flavour was
      investigated using two defined mixed starter cultures encompassing strains of
      Pichia kluyveri and Kluyveromyces marxianus for inoculating cocoa beans in small
      scale tray fermentations. Samples for microbial and metabolite analysis were
      collected at 12-24 hour intervals during 120 h of fermentation. Yeast isolates
      were grouped by (GTG)5-based rep-PCR fingerprinting and identified by sequencing
      of the D1/D2 region of the 26S rRNA gene and the actin gene. Pulsed Field Gel
      Electrophoresis (PFGE) was conducted on isolates belonging to the species P.
      kluyveri and K. marxianus to verify strain level identity with the inoculated
      strains. Furthermore, Denaturing Gradient Gel Electrophoresis (DGGE) was
      performed to follow yeast and bacterial dynamics over time including the presence
      of the bacterial inoculum consisting of Lactobacillus fermentum and Acetobacter
      pasteurianus. Yeast cell counts peaked after 12 h of fermentation with the
      predominant species being identified as Hanseniaspora opuntiae and Hanseniaspora
      thailandica. P. kluyveri and K. marxianus were found to compose 9.3% and 13.5% of
      the yeast population, respectively, after 12 h of fermentation whilst PFGE showed
      that ~88% of all P. kluyveri isolates and 100% of all K. marxianus isolates were
      identical to the inoculated strains. Despite never being the dominant yeast
      species at any stage of fermentation, the un-conched chocolates produced from the
      two inoculated fermentations were judged by sensory analysis to differ in flavour
      profile compared to the spontaneously fermented control. This could indicate that
      yeasts have a greater impact on the sensory qualities of cocoa than previously
      assumed.

PMID- 23866912
TI  - Use of daptomycin in the treatment of vancomycin-resistant enterococcal urinary
      tract infections: a short case series.
AB  - BACKGROUND: Vancomycin-resistant enterococci are a leading cause of hospital
      acquired urinary tract infection and a growing concern for the clinician. The aim
      of this study was to evaluate the effectiveness of daptomycin in the treatment of
      patients with vancomycin-resistant enterococcal urinary tract infection treated
      in our 200-bed community-based institution. METHODS: Patients with confirmed
      symptomatic vancomycin-resistant enterococcal urinary tract infection identified
      by infectious disease consultation between January 1, 2007, and December 8, 2009,
      vancomycin-resistant enterococci-positive urine culture, and urinary symptoms
      and/or pyuria on urinalysis, and treated with daptomycin, were included in this
      case series. Daptomycin was generally administered at a planned dosage regimen of
      >= 5 mg/kg every 24 hours in patients with normal to moderately impaired kidney
      function or every 48 hours in patients with severe kidney disease. Microbiologic
      cure was defined as eradication of vancomycin-resistant enterococci in urine
      cultures taken after the completion of daptomycin treatment. Clinical cure was
      defined by symptom resolution, as assessed by the infectious disease clinician
      caring for the patient. RESULTS: Included in this case series are 10 patients who
      received daptomycin for confirmed vancomycin-resistant enterococcal urinary tract
      infection. Patients had a history of extensive hospital stays. Chart review
      revealed that all levels of kidney function (3, 2, 3, and 2 patients with kidney
      disease classified as normal, mild, moderate, and severe/kidney failure,
      respectively) were represented in the sample and that patients with (n = 5) or
      without (n = 5) previous urinary tract infection and with (n = 3) or without (n =
      7) Foley catheters were included. Treatment with daptomycin achieved clinical
      cure and vancomycin-resistant enterococcal eradication in all cases in this
      series. CONCLUSION: Treatment with daptomycin was well tolerated and effective in
      all patients in this series, regardless of renal function, history of urinary
      tract infection, or Foley catheter use. This study adds to emerging clinical
      evidence that daptomycin is a valuable treatment for vancomycin-resistant
      enterococcal urinary tract infection.

PMID- 23866913
TI  - Diphtheria outbreak with high mortality in northeastern Nigeria.
AB  - SUMMARY A diphtheria outbreak occurred from February to November 2011 in the
      village of Kimba and its surrounding settlements, in Borno State, northeastern
      Nigeria. We conducted a retrospective outbreak investigation in Kimba village and
      the surrounding settlements to better describe the extent and clinical
      characteristics of this outbreak. Ninety-eight cases met the criteria of the case
      definition of diphtheria, 63 (64.3%) of whom were children aged <10 years; 98% of
      cases had never been immunized against diphtheria. None of the 98 cases received
      diphtheria antitoxin, penicillin, or erythromycin during their illness. The
      overall case-fatality ratio was 21.4%, and was highest in children aged 0-4 years
      (42.9%). Low rates of immunization, delayed clinical recognition of diphtheria
      and absence of treatment with antitoxin and appropriate antibiotics contributed
      to this epidemic and its severity.

PMID- 23866914
TI  - Dysregulated Tim-3 expression on natural killer cells is associated with
      increased Galectin-9 levels in HIV-1 infection.
AB  - BACKGROUND: Natural killer (NK) cells constitutively express high levels of Tim
      3, an immunoregulatory molecule recently proposed to be a marker for mature and
      functional NK cells. Whether HIV-1 infection modulates the expression of Tim-3 on
      NK cells, or the levels of its ligand Galectin-9 (Gal-9), and how signaling
      through these molecules affects the NK cell response to HIV-1 remains
      inadequately understood. RESULTS: We analyzed Tim-3 and Gal-9 expression in a
      cohort of 85 individuals with early and chronic HIV-1 infection, and in 13 HIV-1
      seronegative control subjects. HIV-1 infection was associated with reduced
      expression of Tim-3 on NK cells, which was normalized by HAART. Plasma
      concentrations of Gal-9 were higher in HIV-1-infected individuals than in healthy
      individuals. Interestingly, Gal-9 expression in immune cells was significantly
      elevated in early infection, with monocytes and dendritic cells displaying the
      highest expression levels, which correlated with HIV-1 viral loads. In vitro, Gal
      9 triggered Tim-3 downregulation on NK cells as well as NK cell activation.
      CONCLUSIONS: Our data suggest that high expression levels of Gal-9 during early
      HIV-1 infection can lead to enhanced NK cell activity, possibly allowing for
      improved early control of HIV-1. In contrast, persistent Gal-9 production might
      impair Tim-3 activity and contribute to NK cell dysfunction in chronic HIV-1
      infection.

PMID- 23866915
TI  - Development of guidelines for the surveillance of invasive mosquitoes in Europe.
AB  - BACKGROUND: The recent notifications of autochthonous cases of dengue and
      chikungunya in Europe prove that the region is vulnerable to these diseases in
      areas where known mosquito vectors (Aedes albopictus and Aedes aegypti) are
      present. Strengthening surveillance of these species as well as other invasive
      container-breeding aedine mosquito species such as Aedes atropalpus, Aedes
      japonicus, Aedes koreicus and Aedes triseriatus is therefore required. In order
      to support and harmonize surveillance activities in Europe, the European Centre
      for Disease Prevention and Control (ECDC) launched the production of 'Guidelines
      for the surveillance of invasive mosquitoes in Europe'. This article describes
      these guidelines in the context of the key issues surrounding invasive mosquitoes
      surveillance in Europe. METHODS: Based on an open call for tender, ECDC granted a
      pan-European expert team to write the guidelines draft. It content is founded on
      published and grey literature, contractor's expert knowledge, as well as
      appropriate field missions. Entomologists, public health experts and end users
      from 17 EU/EEA and neighbouring countries contributed to a reviewing and
      validation process. The final version of the guidelines was edited by ECDC
      (Additional file 1). RESULTS: The guidelines describe all procedures to be
      applied for the surveillance of invasive mosquito species. The first part
      addresses strategic issues and options to be taken by the stakeholders for the
      decision-making process, according to the aim and scope of surveillance, its
      organisation and management. As the strategy to be developed needs to be adapted
      to the local situation, three likely scenarios are proposed. The second part
      addresses all operational issues and suggests options for the activities to be
      implemented, i.e. key procedures for field surveillance of invasive mosquito
      species, methods of identification of these mosquitoes, key and optional
      procedures for field collection of population parameters, pathogen screening, and
      environmental parameters. In addition, methods for data management and analysis
      are recommended, as well as strategies for data dissemination and mapping.
      Finally, the third part provides information and support for cost estimates of
      the planned programmes and for the evaluation of the applied surveillance
      process. CONCLUSION: The 'Guidelines for the surveillance of invasive mosquitoes
      in Europe' aim at supporting the implementation of tailored surveillance of
      invasive mosquito species of public health importance. They are intended to
      provide support to professionals involved in mosquito surveillance or control,
      decision/policy makers, stakeholders in public health and non-experts in mosquito
      surveillance. Surveillance also aims to support control of mosquito-borne
      diseases, including integrated vector control, and the guidelines are therefore
      part of a tool set for managing mosquito-borne disease risk in Europe.

PMID- 23866916
TI  - HIV voluntary testing and perceived risk among female sex workers in the Mekong
      Delta region of Vietnam.
AB  - INTRODUCTION: HIV voluntary counseling and testing (VCT) comprise an effective
      preventive measure and an entry point to care and support services. We sought to
      assess VCT uptake and HIV-related knowledge and perceived risk among female sex
      workers (FSWs) in five provinces of the Mekong Delta region. METHODS: A cross
      sectional survey was carried out in 1998 FSWs, including both street-based sex
      workers (SSWs) and entertainment-based sex workers (ESWs). RESULTS: High
      proportions of FSWs were aware that using condoms (94.6%), and clean needles
      (34.1%) are preventive measures that reduce the risk of HIV transmission. Some
      FSWs reported avoiding public toilet use (8.6%), physical contacts (16.1%), or
      sharing meals (10.9%) with people living with HIV/AIDS, and preventing mosquito
      bites (20.8%). Twenty-nine percent (29.0%) of FSWs perceived themselves as being
      at risk of HIV infection. Only 32.7% had ever tested for HIV, of whom 54% were
      voluntary for testing. FSWs who ever injected drugs (OR = 0.03, p=0.05), had drug
      injecting clients (OR = 0.07, p<0.01), and had inconsistent condom use with
      husbands or lovers (OR = 0.10, p=0.01) were less likely to have a voluntary test.
      Inconsistent condom use with clients (OR = 13.86, p<0.01), and receiving HIV
      information from radio (OR = 13.28, p<0.05) and communication campaigns (OR =
      6.69, p<0.05), increased the likelihood of VCT uptake. CONCLUSION: Inadequate
      knowledge and some misconceptions about HIV transmission routes and preventive
      measures, low perceived risk of HIV infection, and low VCT uptake were observed
      among FSWs in the Mekong Delta region. Interventions to improve their knowledge
      and self-efficacy, reduce risky behaviors, and encourage VCT uptake and early
      access to health care services are necessary to prevent HIV transmission in this
      region.

PMID- 23866917
TI  - Design and methodology of a community-based cluster-randomized controlled trial
      for dietary behaviour change in rural Kerala.
AB  - BACKGROUND: Interventions targeting lifestyle-related risk factors and non
      communicable diseases have contributed to the mainstream knowledge necessary for
      action. However, there are gaps in how this knowledge can be translated for
      practical day-to-day use in complex multicultural settings like that in India.
      Here, we describe the design of the Behavioural Intervention for Diet study,
      which was developed as a community-based intervention to change dietary behaviour
      among middle-income households in rural Kerala. METHODS: This was a cluster
      randomized controlled trial to assess the effectiveness of a sequential stage
      matched intervention to bring about dietary behaviour change by targeting the
      procurement and consumption of five dietary components: fruits, vegetables, salt,
      sugar, and oil. Following a step-wise process of pairing and exclusion of
      outliers, six out of 22 administrative units in the northern part of Trivandrum
      district, Kerala state were randomly selected and allocated to intervention or
      control arms. Trained community volunteers carried out the data collection and
      intervention delivery. An innovative tool was developed to assess household
      readiness-to-change, and a household measurement kit and easy formulas were
      introduced to facilitate the practical side of behaviour change. The 1-year
      intervention included a household component with sequential stage-matched
      intervention strategies at 0, 6, and 12 months along with counselling sessions,
      telephonic reminders, and home visits and a community component with general
      awareness sessions in the intervention arm. Households in the control arm
      received information on recommended levels of intake of the five dietary
      components and general dietary information leaflets. DISCUSSION: Formative
      research provided the knowledge to contextualise the design of the study in
      accordance with socio-cultural aspects, felt needs of the community, and the
      ground realities associated with existing dietary procurement, preparation, and
      consumption patterns. The study also addressed two key issues, namely the central
      role of the household as the decision unit and the long-term sustainability
      through the use of existing local and administrative networks and community
      volunteers.

PMID- 23866918
TI  - Host traits explain the genetic structure of parasites: a meta-analysis.
AB  - Gene flow maintains the genetic integrity of species over large spatial scales,
      and dispersal maintains gene flow among separate populations. However, body size
      is a strong correlate of dispersal ability, with small-bodied organisms being
      poor dispersers. For parasites, small size may be compensated by using their
      hosts for indirect dispersal. In trematodes, some species use only aquatic hosts
      to complete their life cycle, whereas others use birds or mammals as final hosts,
      allowing dispersal among separate aquatic habitats. We performed the first test
      of the universality of the type of life cycle as a driver of parasite dispersal,
      using a meta-analysis of 16 studies of population genetic structure in 16
      trematode species. After accounting for the geographic scale of a study, the
      number of populations sampled, and the genetic marker used, we found the type of
      life cycle to be the best predictor of genetic structure (Fst): trematode species
      bound to complete their life cycle within water showed significantly more
      pronounced genetic structuring than those leaving water through a bird or mammal
      host. This finding highlights the dependence of parasites on host traits for
      their dispersal, suggesting that genetic differentiation of parasites reflects
      the mobility of their hosts.

PMID- 23866919
TI  - LRP1 is critical for the surface distribution and internalization of the NR2B
      NMDA receptor subtype.
AB  - BACKGROUND: The N-methyl-D-aspartate receptors are key mediators of excitatory
      transmission and are implicated in many forms of synaptic plasticity. These
      receptors are heterotetrameres consisting of two obligatory NR1 and two
      regulatory subunits, usually NR2A or NR2B. The NR2B subunits are abundant in the
      early postnatal brain, while the NR2A/NR2B ratio increases during early postnatal
      development. This shift is driven by NMDA receptor activity. A functional
      interplay of the Low Density Lipoprotein Receptor Related Protein 1 (LRP1) NMDA
      receptor has already been reported. Such abilities as interaction of LRP1 with
      NMDA receptor subunits or its important role in tPa-mediated NMDA receptor
      signaling were already demonstrated. Moreover, mice harboring a conditional
      neuronal knock-out mutation of the entire Lrp1 gene display NMDA-associated
      behavioral changes. However, the exact role of LRP1 on NMDA receptor function
      remains still elusive. RESULTS: To provide a mechanistic explanation for such
      effects we investigated whether an inactivating knock-in mutation into the NPxY2
      motif of LRP1 might influence the cell surface expression of LRP1 and NMDA
      receptors in primary cortical neurons. Here we demonstrate that a knock-in into
      the NPxY2 motif of LRP1 results in an increased surface expression of LRP1 and
      NR2B NMDA receptor subunit due to reduced endocytosis rates of LRP1 and the NR2B
      subunit in primary neurons derived from LRP1DeltaNPxY2 animals. Furthermore, we
      demonstrate an altered phosphorylation pattern of S1480 and Y1472 in the NR2B
      subunit at the surface of LRP1DeltaNPxY2 neurons, while the respective kinases
      Fyn and casein kinase II are not differently regulated compared with wild type
      controls. Performing co-immunoprecipitation experiments we demonstrate that
      binding of LRP1 to NR2B might be linked by PSD95, is phosphorylation dependent
      and this regulation mechanism is impaired in LRP1DeltaNPxY2 neurons. Finally, we
      demonstrate hyperactivity and changes in spatial and reversal learning in
      LRP1DeltaNPxY2 mice, confirming the mechanistic interaction in a physiological
      readout. CONCLUSIONS: In summary, our data demonstrate that LRP1 plays a critical
      role in the regulation of NR2B expression at the cell surface and may provide a
      mechanistic explanation for the behavioral abnormalities detected in neuronal
      LRP1 knock-out animals reported earlier.

PMID- 23866920
TI  - A feasibility study of brief group-based acceptance and commitment therapy for
      chronic pain in general practice: recruitment, attendance, and patient views.
AB  - BACKGROUND: Acceptance and commitment therapy (ACT), a form of cognitive
      behavioral therapy, may help meet a need for accessible and cost-effective
      treatments for chronic pain. ACT has a growing evidence base, but has not yet
      been tested within general practice settings. AIM: The purpose of the present
      study was to examine the feasibility of conducting a full-scale randomized
      controlled trial of ACT in general practice. METHODS: A total of 481 potential
      participants with chronic pain identified from general practice in southwest
      England were invited into a treatment trial. Subsequently, 102 (21.2%) of those
      invited were screened, and 73 (71.6%) of those screened were allocated to ACT
      plus usual care or usual care alone. The ACT treatment included four, four-hour
      group-based sessions over two weeks. RESULTS: Twenty-six (70.3%) of the patients
      allocated to ACT attended three or four sessions. Those who received ACT rated it
      as credible in a short survey, with Mdn rating 7.0 on a 0-10 scale, across five
      credibility items. During a post-treatment interview considering 12 aspects of
      the study from invitation to treatment termination, a median of 79.2% of
      participants rated the aspects 'acceptable.' Qualitative data from the interviews
      showed a mixed picture of patient experiences, revealing possible tensions
      between patients' wishes to avoid discomfort and confusion, and treatment methods
      that explicitly ask patients to, in essence, 'live with' some discomfort and
      confusion. CONCLUSIONS: These data suggest that further study of ACT, as a
      treatment for chronic pain, is feasible in general practice and it may be
      possible to further optimize the treatment experience.

PMID- 23866921
TI  - Contemporary adjuvant polymethyl methacrylate cementation optimally limits
      recurrence in primary giant cell tumor of bone patients compared to bone
      grafting: a systematic review and meta-analysis.
AB  - BACKGROUND: Reports of recurrence following restructuring of primary giant cell
      tumor (GCT) defects using polymethyl methacrylate (PMMA) bone cementation or
      allogeneic bone graft with and without adjuvants for intralesional curettage vary
      widely. Systematic review and meta-analysis were conducted to investigate
      efficacy of PMMA bone cementation and allogeneic bone grafting following
      intralesional curettage for GCT. METHODS: Medline, EMBASE, Google Scholar, and
      Cochrane databases were searched for studies reporting GCT of bone treatment with
      PMMA cementation and/or bone grafting with or without adjuvant therapy following
      intralesional curettage of primary GCTs. Pooled risk ratios and 95% confidence
      intervals (CIs) for local recurrence risks were calculated by fixed-effects
      methods. RESULTS: Of 1,690 relevant titles, 6 eligible studies (1,293 patients)
      spanning March 2008 to December 2011 were identified in published data. Treatment
      outcomes of PMMA-only (n = 374), bone graft-only (n = 436), PMMA with or without
      adjuvant (PMMA + adjuvant; n = 594), and bone graft filling with or without
      adjuvant (bone graft + adjuvant; n = 699) were compared. Bone graft-only patients
      exhibited higher recurrence rates than PMMA-treated patients (RR 2.09, 95% CI
      (1.64, 2.66), Overall effect: Z = 6.00; P <0.001), and bone graft + adjuvant
      patients exhibited higher recurrence rates than PMMA + adjuvant patients (RR
      1.66, 95% CI (1.21, 2.28), Overall effect: Z = 3.15, P = 0.002). CONCLUSIONS:
      Local recurrence was minimal in PMMA cementation patients, suggesting that PMMA
      is preferable for routine clinical restructuring in eligible GCT patients.
      Relationships between tumor characteristics, other modern adjuvants, and
      recurrence require further exploration.

PMID- 23866922
TI  - The degree of urbanization across the globe is not reflected in the delta(15)N of
      seagrass leaves.
AB  - Many studies show that seagrass delta(15)N ratios increase with the amount of
      urbanization in coastal watersheds. However, there is little information on the
      relationship between urbanization and seagrass delta(15)N ratios on a global
      scale. We performed a meta-analysis on seagrass samples from 79 independent
      locations to test if seagrass delta(15)N ratios correlate with patterns of
      population density and fertilizer use within a radius of 10-200 km around the
      sample locations. Our results show that seagrass delta(15)N ratios are more
      influenced by intergeneric and latitudinal differences than the degree of
      urbanization or the amount of fertilizer used in nearby watersheds. The positive
      correlation between seagrass delta(15)N ratios and latitude hints at an
      underlying pattern in discrimination or a latitudinal gradient in the (15)N
      isotopic signature of nitrogen assimilated by the plants. The actual mechanisms
      responsible for the correlation between delta(15)N and latitude remain unknown.

PMID- 23866923
TI  - Free-field characterization via directional transmission through a nanoaperture.
AB  - : We propose a scheme based on extraordinary transmission of light through a
      single nanoaperture, surrounded by periodic corrugations, for direct
      characterization of focal-region optical fields with subwavelength-scale
      structure. We describe the design of the device on the basis of rigorous
      diffraction theory and fabricate a prototype using a process that involves
      electron beam lithography, dry etching, and template stripping. First
      experimental results performed with a transmission-type confocal optical
      microscope demonstrate the potential of the method. 

PMID- 23866925
TI  - Determinants of relative and absolute concentration indices: evidence from 26
      European countries.
AB  - INTRODUCTION: The aim of publicly-provided health care is generally not only to
      produce health, but also to decrease variation in health by socio-economic
      status. The aim of this study is to measure to what extent this goal has been
      obtained in various European countries and evaluate the determinants of
      inequalities within countries, as well as cross-country patterns with regard to
      different cultural, institutional and social settings. METHODS: The data utilized
      in this study provides information on 440,000 individuals in 26 European
      countries and stem from The European Union Statistics on Income and Living
      Conditions (EU-SILC) collected in 2007. As measures of income-related inequality
      in health both the relative concentration indices and the absolute concentration
      indices are calculated. Further, health inequality in each country is decomposed
      into individual-level determinants and cross-country comparisons are made to shed
      light on social and institutional determinants. RESULTS: Income-related health
      inequality favoring the better-off is observed for all the 26 European countries.
      In terms of within-country determinants inequality is mainly explained by income,
      age, education, and activity status. However, the degree of inequality and
      contribution of each determinant to inequality varies considerably between
      countries. Aggregate bivariate linear regressions show that there is a positive
      association between health-income inequality in Europe and public expenditure on
      education. Furthermore, a negative relationship between health-income inequality
      and income inequality was found when individual employee cash income was used in
      the health-concentration measurement. Using that same income measure, health
      income inequality was found to be higher in the Nordic countries than in other
      areas, but this result is sensitive to the income measure chosen. CONCLUSIONS:
      The findings indicate that institutional determinants partly explain income
      related health inequalities across countries. The results are in accordance with
      previously published theories hypothesizing social mobility as the explanation
      for differences in health-income inequalities between countries and higher health
      income inequality could be a result of lower income inequality.

PMID- 23866924
TI  - Effect of berberine on insulin resistance in women with polycystic ovary
      syndrome: study protocol for a randomized multicenter controlled trial.
AB  - BACKGROUND: Insulin resistance and hyperinsulinemia play a key role in the
      pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by
      hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on
      pelvic scanning. Insulin resistance is significantly associated with the long
      term risks of metabolic syndrome and cardiovascular disease. Berberine has
      effects on insulin resistance but its use in women with PCOS has not been fully
      investigated. In this paper, we present a research design evaluating the effects
      of berberine on insulin resistance in women with PCOS. METHODS/DESIGN: This is a
      multicenter, randomized, placebo-controlled and double-blind trial. A total of
      120 patients will be enrolled in this study and will be randomized into two
      groups. Berberine or placebo will be taken orally for 12 weeks. The primary
      outcome is the whole body insulin action assessed with the hyperinsulinemic
      euglycemic clamp. DISCUSSION: We postulate that women with PCOS will have
      improved insulin resistance following berberine administration. TRIAL
      REGISTRATION: This study is registered at ClinicalTrials.gov, NCT01138930.

PMID- 23866926
TI  - Efficacy of a combination of 10% imidacloprid and 4.5% flumethrin (Seresto(r)) in
      slow release collars to control ticks and fleas in highly infested dog
      communities.
AB  - BACKGROUND: Dog communities living in kennels are at high risk of being infected
      by ticks and fleas. In spite of the indubitable efficacy of several topical
      ectoparasiticides registered for the control of ectoparasites in dogs, the short
      period of action and the price of these products limit their use in dog
      communities. This paper reports on the efficacy of imidacloprid/flumethrin slow
      release collars to cure dogs highly infested with ectoparasites and to prevent
      infestations for 8 months in a refuge with a history of unsuccessful
      environmental treatments. METHODS: A total of 82 dogs were collared with slow
      release collars containing a formulation of imidacloprid 10% / flumethrin 4.5%.
      Dogs were followed-up for ectoparasite presence after 2, 7 and 14 days and
      thereafter biweekly up to 90 days. Furthermore, dogs were examined for
      ectoparasites whilst replacing collars 8 months after their application. RESULTS:
      At the time of treatment 79 (96.3%) out of 82 included dogs were heavily infested
      by ticks and 53 (68.8%) out of the 77 combed dogs were infested by fleas. Tick
      infested dogs had an estimated mean intensity of 46.9 (+/- 65.7), while flea
      infested animals had a load between 20 and 50 fleas. In addition, some of the
      flea infested dogs (18.9%) were presenting signs of flea allergic dermatitis
      (FAD). Two days after treatment, 49 (60.5%) and 9 (11.7%) dogs were still
      infested by live ticks and fleas, respectively. However, the mean intensity of
      ticks decreased to 3.5 (+/- 4.3) with a reduction of 92.5%. Except for sporadic
      cases, no attached ectoparasites were found on dogs from the day 14 visit until
      the end of the investigation. Cases of FAD resolved without any other treatment
      within 30 days. CONCLUSIONS: Ticks and fleas represent a constant hazard for dog
      populations. Therefore, in particular settings, such as dog refuges, sustainable
      and long-term strategies to control ectoparasite infestations are needed. Based
      on the observed evidence of efficacy, long-term duration and safety, the
      imidacloprid/flumethrin slow release collars can be regarded as an efficacious
      and sustainable means for ectoparasite control and for treatment of FAD in high
      risk dog communities.

PMID- 23866927
TI  - Planting question marks.

PMID- 23866928
TI  - Comparison of legislation, regulations and national health strategies for
      palliative care in seven European countries (Results from the Europall Research
      Group): a descriptive study.
AB  - BACKGROUND: According to EU policy, anyone in need of palliative care should be
      able to have access to it. It is therefore important to investigate which
      palliative care topics are subject to legislation and regulations in Europe and
      how these are implemented in (national) health care plans. This paper aims to
      deliver a structured overview of the legislation, existing regulations and the
      different health care policies regarding palliative care in seven European
      countries. METHODS: In 2008 an inventory of the organisation of palliative care
      was developed by the researchers of the Europall project. Included were two open
      questions about legislation, regulations, and health policy in palliative care.
      This questionnaire was completed using palliative care experts selected from
      Belgium, England, France, Germany, the Netherlands, Poland and Spain.
      Additionally, (grey) literature on palliative care health policy and regulations
      from the participating countries was collected to complete the inventory.
      Comparative analysis of country specific information was performed afterwards.
      RESULTS: In all countries palliative care regulations and policies existed
      (either in laws, royal decrees, or national policies). An explicit right to
      palliative care was mentioned in the Belgium, French and German law. In addition,
      access to palliative care was mentioned by all countries, varying from explicit
      regulations to policy intentions in national plans. Also, all countries had a
      national policy on palliative care, although sometimes mainly related to national
      cancer plans. Differences existed in policy regarding palliative care leave,
      advance directives, national funding, palliative care training, research, opioids
      and the role of volunteers. CONCLUSIONS: Although all included European countries
      have policies on palliative care, countries largely differ in the presence of
      legislation and regulations on palliative care as well as the included topics.
      European healthcare policy recommendations should support palliative care access
      across Europe.

PMID- 23866929
TI  - Large-cell neuroendocrine carcinoma of lung with epidermal growth factor receptor
      (EGFR) gene mutation and co-expression of adenocarcinoma markers: a case report
      and review of the literature.
AB  - PURPOSE: A high rate of response to treatment with epidermal growth factor
      receptor tyrosine kinase inhibitor (EGFR-TKI) has been observed in certain
      patients (women, of East Asian ethnicity, with non-smoking history and
      adenocarcinoma histology) with mutations in exons 18 to 21 of the tyrosine kinase
      domain of EGFR. Some cases of high-grade neuroendocrine carcinoma of the lung
      harboring mutations have been sporadically reported. METHODS: We describe the
      case of a 78-year-old woman with large-cell neuroendocrine carcinoma of the lung,
      with mutation in exon 21 L858R and co-expression of adenocarcinoma markers.
      RESULTS: A mass (3.0 cm in diameter) was identified in the inferior lobe of the
      left lung, accompanied by metastases into ipsilateral mediastinal lymph nodes and
      elevations of serum pro-gastrin-releasing peptide and carcinoembryonic antigen.
      Initial transbronchial brushing cytology suggested high-grade neuroendocrine
      carcinoma favoring small-cell carcinoma in poorly smeared and degenerated
      preparations, and revealed exon 21 L858R mutation. Re-enlargement of the cancer
      and bone metastases was observed after chemotherapy, and further testing
      suggested large-cell neuroendocrine carcinoma with immunoreactivity to markers of
      primary lung adenocarcinoma and L858R mutation. High-grade neuroendocrine
      carcinoma with mutations in the tyrosine kinase domain of EGFR may be associated
      with adenocarcinoma, as reviewed from the literature and may also apply to our
      case. CONCLUSIONS: EGFR-TKI could provide better quality of life and survival in
      patients with advanced or relapsed high-grade neuroendocrine carcinoma with EGFR
      gene mutations. Further studies in this respect are warranted.

PMID- 23866930
TI  - Phenotypic and genotypic identification of streptococci and related bacteria
      isolated from bovine intramammary infections.
AB  - BACKGROUND: Streptococcus spp. and other Gram-positive, catalase-negative cocci
      (PNC) form a large group of microorganisms which can be found in the milk of cows
      with intramammary infection. The most frequently observed PNC mastitis pathogens
      (major pathogens) are Streptococcus uberis, Strep. dysgalactiae, and Strep.
      agalactiae. The remaining PNC include a few minor pathogens and a large
      nonpathogenic group. Improved methods are needed for the accurate identification
      and differentiation of PNC. A total of 151 PNC were collected from cows with
      intramammary infection and conclusively identified by 16S rRNA sequencing as
      reference method. Nine phenotypic microbiological tests (alpha-hemolysis, CAMP
      reaction, esculin hydrolysis, growth on kanamycin esculin azide agar and on
      sodium chloride agar, inulin fermentation, hippurate hydrolysis, leucine
      aminopeptidase and pyrrolidonyl peptidase activity), multiplex PCR for the three
      major pathogens (target genes for Strep. uberis, Strep. dysgalactiae and Strep.
      agalactiae: pauA, 16S rRNA, and sklA3, respectively), and mass spectroscopy using
      the matrix-assisted laser desorption ionization-time of flight (MALDI-TOF MS)
      were evaluated for the diagnosis and discrimination of the three clinically most
      relevant PNC. RESULTS: The probability that a strain of Strep. uberis, Strep.
      dysgalactiae and Strep. agalactiae was correctly identified by combining the
      results of the 9 phenotypic tests was 92%, 90%, and 100%, respectively. Applying
      the multiplex PCR, all strains of the three major pathogens were correctly
      identified and no false positive results occurred. Correct identification was
      observed for all strains of Strep. uberis and Strep. agalactiae using MALDI-TOF
      MS. In the case of Strep. dysgalactiae, some variability was observed at the
      subspecies level, but all strains were allocated to one single cluster.
      CONCLUSIONS: The results of the present study show that reliable identification
      of the clinically most relevant PNC (Strep. uberis, Strep. agalactiae and Strep.
      dysgalactiae) can be obtained by use of a combination of colony morphology,
      hemolysis type and catalase reaction, and a multiplex PCR with specific primers
      restricted to these 3 pathogens. The MALDI-TOF MS is a fast method that shows
      promising results, although identification of Strep. dysgalactiae at the
      subspecies level is not yet satisfactory.

PMID- 23866931
TI  - Quantification of effectiveness of bilateral and unilateral neuromodulation in
      the rat bladder rhythmic contraction model.
AB  - BACKGROUND: Using the isovolumetric bladder rhythmic contraction (BRC) model in
      anesthetized rats, we have quantified the responsiveness to unilateral and
      bilateral stimulation of the L6 spinal nerve (SN) and characterized the
      relationship between stimulus intensity and inhibition of the bladder micturition
      reflex. METHODS: A wire electrode was placed under either one or both of the L6
      SN roots. A cannula was placed into the bladder via the urethra and the urethra
      was ligated. Saline infusion induced BRC. RESULTS: At motor threshold (T mot)
      intensity, SN stimulation of both roots (10 Hz) for 10 min reduced bladder
      contraction frequency from 0.63 +/- 0.04 to 0.17 +/- 0.09 contractions per min
      (26 +/- 14% of baseline control; n = 10, p < 0.05). However, the same intensity
      of unilateral stimulation (n = 15) or sequential stimulation of both SNs (e.g. 5
      min per side alternatively for a total of 10 min or 20 min) was less efficacious.
      The greater sensitivity to bilateral stimulation is not dependent upon precise
      bilateral timing of the stimulation pulses. Bilateral stimulation also produced
      both acute and prolonged- inhibition on bladder contractions in a stimulation
      intensity dependent fashion. CONCLUSIONS: Using the bladder rhythmic contraction
      model, bilateral stimulation was more effective than unilateral stimulation of
      the SN. Clinical testing should be conducted to further compare efficacies of
      unilateral and bilateral stimulation. Bilateral stimulation may allow the use of
      lower stimulation intensities to achieve higher efficacy for neurostimulation
      therapies on urinary tract control.

PMID- 23866933
TI  - Trichomonad parasite infection in four species of Columbidae in the UK.
AB  - Trichomonas gallinae is an emerging pathogen in wild birds, linked to recent
      declines in finch (Fringillidae) populations across Europe. Globally, the main
      hosts for this parasite are species of Columbidae (doves and pigeons); here we
      carry out the first investigation into the presence and incidence of Trichomonas
      in four species of Columbidae in the UK, through live sampling of wild-caught
      birds and subsequent PCR. We report the first known UK cases of Trichomonas
      infection in 86% of European Turtle Doves Streptopelia turtur sampled, along with
      86% of Eurasian Collared Doves Streptopelia decaocto, 47% of Woodpigeons Columba
      palumbus and 40% of Stock Doves Columba oenas. Birds were more likely to be
      infected if the farm provided supplementary food for gamebirds. We found three
      strains of T. gallinae and one strain clustering within the Trichomonas tenax
      clade, not previously associated with avian hosts in the UK. One T. gallinae
      strain was identical at the ITS/5.8S/ITS2 ribosomal region to that responsible
      for the finch trichomonosis epizootic. We highlight the importance of increasing
      our knowledge of the diversity and ecological implications of Trichomonas
      parasites in order further to understand the sub-clinical impacts of parasite
      infection.

PMID- 23866932
TI  - The optic chiasm: a turning point in the evolution of eye/hand coordination.
AB  - The primate visual system has a uniquely high proportion of ipsilateral retinal
      projections, retinal ganglial cells that do not cross the midline in the optic
      chiasm. The general assumption is that this developed due to the selective
      advantage of accurate depth perception through stereopsis. Here, the hypothesis
      that the need for accurate eye-forelimb coordination substantially influenced the
      evolution of the primate visual system is presented. Evolutionary processes may
      change the direction of retinal ganglial cells. Crossing, or non-crossing, in the
      optic chiasm determines which hemisphere receives visual feedback in reaching
      tasks. Each hemisphere receives little tactile and proprioceptive information
      about the ipsilateral hand. The eye-forelimb hypothesis proposes that abundant
      ipsilateral retinal projections developed in the primate brain to synthesize, in
      a single hemisphere, visual, tactile, proprioceptive, and motor information about
      a given hand, and that this improved eye-hand coordination and optimized the size
      of the brain. If accurate eye-hand coordination was a major factor in the
      evolution of stereopsis, stereopsis is likely to be highly developed for activity
      in the area where the hands most often operate.The primate visual system is
      ideally suited for tasks within arm's length and in the inferior visual field,
      where most manual activity takes place. Altering of ocular dominance in reaching
      tasks, reduced cross-modal cuing effects when arms are crossed, response of
      neurons in the primary motor cortex to viewed actions of a hand, multimodal
      neuron response to tactile as well as visual events, and extensive use of
      multimodal sensory information in reaching maneuvers support the premise that
      benefits of accurate limb control influenced the evolution of the primate visual
      system. The eye-forelimb hypothesis implies that evolutionary change toward
      hemidecussation in the optic chiasm provided parsimonious neural pathways in
      animals developing frontal vision and visually guided forelimbs, and also
      suggests a new perspective on vision convergence in prey and predatory animals. 

PMID- 23866934
TI  - How life turned out one year after attending a multidisciplinary pulmonary
      rehabilitation programme in primary health care.
AB  - AIM: To describe experiences among patients with chronic obstructive pulmonary
      disease (COPD) of the lasting usefulness one year after participating in a
      multidisciplinary pulmonary rehabilitation (PR) programme in a primary health
      care (PHC) setting. BACKGROUND: COPD affects patients' functioning in daily life.
      In a previous study, the patients participated in a programme for PR and were
      found to increase their functional capacity, quality of life and decrease
      exacerbations. The present study aims to provide a deeper understanding of the
      experience of participating in the programme. DESIGN: The study has a
      descriptive, qualitative design and is part of a longitudinal study on a
      multidisciplinary programme for PR of patients with COPD. METHOD: Semi-structured
      interviews with 20 participants were performed and data analysed by qualitative
      content analysis. FINDINGS: The findings are presented in one theme that
      illustrates the participants' experience of their current situation; I live life
      at my own pace, and three sub-themes illustrating this experience related to the
      participation in the programme; Awareness of limitations in my life; Regained
      control over my life; and No change in my life. CONCLUSION: Irrespective of
      whether the patients had already found their own strategies for managing the
      disease or whether the programme changed their lives, they lived their lives at
      their own pace. However, their lives were shadowed by worry. RELEVANCE TO
      CLINICAL PRACTICE: A multidisciplinary programme for PR in PHC could be an
      alternative for patients suffering from COPD, in order to facilitate for them in
      their daily life. It is suggested that the inclusion of patients in such groups
      should be based on each individual's need based on symptoms or functional
      capacity in everyday life, not based on spirometry values.

PMID- 23866935
TI  - Renal collecting duct carcinoma with extensive coagulative necrosis mimicking
      anemic infarct: report of a case and the literature review.
AB  - Collecting duct carcinoma (CDC) with a mass of coagulative necrosis is very rare.
      We report here a case of CDC with extensive geographic coagulative necrosis
      mimicking anemic infarct with tumor cells embedded around the necrotic foci in a
      73-years-old man. Histopathological examination showed that tumor nests near the
      necrotic foci were arranged as angulated tubules, tubulopapillary and glandular
      structures. Neoplastic cells had moderate to abundant eosinophilic cytoplasm and
      large hyperchromatic nuclei with prominent nucleoli as Fuhrman nuclear grade 3 or
      4. The tumor cells were positive for pan-Cytokeratin, Vimentin, E-cadherin, CD10,
      and CK7, confirming the diagnosis as CDC. The patient is still alive 6 months
      later from nephrectomy, a long time following up is needed to learn the
      prognosis. Conclusively, morphology from different portions of the lesion,
      immunohistochemical stain and the combination analysis of the radiological
      features is essential to make a precise pathological diagnosis of CDC. And CDC
      should also be distinguished from clear cell renal cell carcinoma, renal
      medullary carcinoma, urothelial carcinoma with glandular differentiation, renal
      neuroendocrine tumor, renal epithelioid angiomyolipoma, renal pigmented
      paraganglioma and renal mesenchymal chondrosarcoma etc. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1264270525975030.

PMID- 23866936
TI  - Diagnosis and treatment of cystic renal cell carcinoma.
AB  - BACKGROUND: To summarize the diagnosis and treatment of cystic renal cell
      carcinoma (CRCC). METHODS: A retrospective study was conducted on 13 patients
      with CRCC at our center from August 2004 to April 2012. The pathologic features,
      clinical manifestation, imaging characteristics, treatment, and prognosis of CRCC
      were summarized according to available literature. RESULTS: Of the 13 patients,
      11 were diagnosed with CRCC by preoperative B ultrasonography and computed
      tomography (CT) scan. The remaining two cases were initially misdiagnosed with
      simple renal cysts. Open radical nephrectomy was performed on two of the 13
      cases, laparoscopic radical nephrectomy on seven cases, and open partial
      nephrectomy on four cases. All diagnoses of CRCC were confirmed by pathological
      examination. After the operation, all patients had an uneventful recovery. During
      the follow-up (range, 6-60 months), the serum creatinine concentrations and GFR
      of the partially removed kidneys remained stable within the normal range. No
      tumor recurrence or metastasis occurred. CONCLUSIONS: By combining imaging
      examinations (B ultrasonography and CT scan) with intraoperative pathological
      examination, most cases of CRCC can be diagnosed and treated promptly and
      accurately. Nephrectomy is the first-line therapy. Nephron-sparing surgery should
      be preferred for CRCC. After a successful operation, the prognosis of CRCC is
      good.

PMID- 23866937
TI  - Efficacy of dexamethasone in the prophylaxis of nausea and vomiting during the
      postoperative period of laparoscopic cholecystectomy.
AB  - OBJECTIVE: To verify the efficacy of dexamethasone in the prophylaxis of nausea
      and vomiting in patients submitted to laparoscopic cholecystectomy. METHODS: This
      was a systematic review of the literature through the MEDLINE, Embase, and LILACS
      databases. Only controlled and randomized clinical trials comparing dexamethasone
      to placebo in the prophylaxis of nausea and vomiting in patients submitted to
      laparoscopic cholecystectomy were included. RESULTS: The results of this review
      were based on data from 12 controlled and randomized clinical trials, totaling
      947 patients. The group of patients who received preoperative dexamethasone
      showed lower incidence of nausea (number needed to treat [NNT]=7), vomiting
      (NNT=7), and need for smaller doses of rescue antiemetics (NNT=6). CONCLUSION:
      The preoperative infusion of 8 mg of dexamethasone decreases the risk of
      complications in the postoperative period for patients submitted to laparoscopic
      cholecystectomy.

PMID- 23866938
TI  - Frequency of cardiovascular risk factors before and 6 and 12 months after
      bariatric surgery.
AB  - OBJECTIVE: To compare the frequency of cardiovascular risk factors (CVRFs) in
      obese patients of the Brazilian Unified Health System (Sistema Unico de Saude -
      SUS) with indication of bariatric surgery during the preoperative period and
      after the sixth month and the first year of the procedure. METHODS: An
      observational, longitudinal, prospective, and analytical study was performed,
      with consecutive selection of obese patients with indication for surgery referred
      to preoperative cardiac evaluation. The protocol consisted of: medical history,
      physical examination, electrocardiogram, echocardiogram, and biochemical
      analysis. This study analyzed the following variables: weight, body mass index
      (BMI), waist circumference (WC), systemic arterial hypertension (SAH), diabetes
      mellitus type 2(DM), dyslipidemia (high LDL cholesterol; low HDL cholesterol;
      hypertriglyceridemia), and metabolic syndrome (MS). The chi-squared test and the
      Tukey-Kramer method were used for statistical analysis. RESULTS: The sample was
      composed of 96 obese people, among which 86 were women, aged between 18 and 58
      years old (median 35 years old). At the end of six months, significant reductions
      of 88%, 95%, 71%, 89%, and 80% in the frequency of SAH, high LDL cholesterol,
      hypertriglyceridemia, DM, and MS could already be observed. A significant and
      small reduction in the frequency of low HDL cholesterol (24%) and abnormal WC
      (31%) was observed only at the end of 12 months. After six months and one year,
      weight and BMI experienced reductions of 33.4kg and 44.3kg, and 13.1kg/m(2) and
      17.2kg/m(2), respectively. CONCLUSION: The positive impact on weight loss and the
      reduction in BMI, WC, and in the frequency of CVRFs are already extremely
      significant after six months and remain so one year after bariatric surgery.

PMID- 23866939
TI  - The effect of the radio-protective agents ethanol, trimethylglycine, and beer on
      survival of X-ray-sterilized male Aedes aegypti.
AB  - BACKGROUND: Sterile Insect Technique (SIT) has been successfully implemented to
      control, and in some cases, eradicate, dipteran insect populations. SIT has great
      potential as a mosquito control method. Different sterilization methods have been
      used on mosquitoes ranging from chemosterilization to genetically modified
      sterile male mosquito strains; however, sterilization with ionizing radiation is
      the method of choice for effective sterilization of male insects for most
      species. The lack of gentle radiation methods has resulted in significant
      complications when SIT has been applied to mosquitoes. Several studies report
      that irradiating mosquitoes resulted in a decrease in longevity and mating
      success compared to unirradiated males. The present study explored new protocols
      for mosquito sterilization with ionizing radiation that minimized detrimental
      effects on the longevity of irradiated males. METHODS: We tested three compounds
      that have been shown to act as radioprotectors in the mouse model system -
      ethanol, trimethylglycine, and beer. Male Aedes aegypti were treated with one of
      three chosen potential radioprotectors and were subsequently irradiated with
      identical doses of long-wavelength X-rays. We evaluated the effect of these
      radioprotectors on the longevity of male mosquito after irradiation. RESULTS: We
      found that X-ray irradiation with an absorbed dose of 1.17 gy confers complete
      sterility. Irradiation with this dose significantly shortened the lifespan of
      male mosquitoes and all three radioprotectors tested significantly enhanced the
      lifespan of irradiated mosquito males. CONCLUSION: Our results suggest that
      treatment with ethanol, beer, or trimethylglycine before irradiation can be used
      to enhance longevity in mosquitoes.

PMID- 23866940
TI  - Self-reported occupational exposure to HIV and factors influencing its management
      practice: a study of healthcare workers in Tumbi and Dodoma Hospitals, Tanzania.
AB  - BACKGROUND: Blood borne infectious agents such as hepatitis B virus (HBV),
      hepatitis C virus (HCV) and human immune deficiency virus (HIV) constitute a
      major occupational hazard for healthcare workers (HCWs). To some degree it is
      inevitable that HCWs sustain injuries from sharp objects such as needles,
      scalpels and splintered bone during execution of their duties. However, in
      Tanzania, there is little or no information on factors that influence the
      practice of managing occupational exposure to HIV by HCWs. This study was
      conducted to determine the prevalence of self-reported occupational exposure to
      HIV among HCWs and explore factors that influence the practice of managing
      occupational exposure to HIV by HCWs in Tanzania. METHODS: Self-administered
      questionnaire was designed to gather information of healthcare workers'
      occupational exposures in the past 12 months and circumstances in which these
      injuries occurred. Practice of managing occupational exposure was assessed by the
      following questions: RESULTS: Nearly half of the HCWs had experienced at least
      one occupational injury in the past 12 months. Though most of the occupational
      exposures to HIV were experienced by female nurses, non-medical hospital staff
      received PEP more frequently than nurses and doctors. Doctors and nurses
      frequently encountered occupational injuries in surgery room and labor room
      respectively. HCWs with knowledge on the possibility of HIV transmission and
      those who knew whom to contact in event of occupational exposure to HIV were less
      likely to have poor practice of managing occupational exposure. CONCLUSION:
      Needle stick injuries and splashes are common among HCWs at Tumbi and Dodoma
      hospitals. Knowledge of the risk of HIV transmission due to occupational exposure
      and knowing whom to contact in event of exposure predicted practice of managing
      the exposure. Thus provision of health education on occupational exposure may
      strengthen healthcare workers' practices to manage occupational exposure.

PMID- 23866941
TI  - Successful reduction of hospital-acquired methicillin-resistant Staphylococcus
      aureus in a urology ward: a 10-year study.
AB  - BACKGROUND: To eradicate hospital-acquired methicillin-resistant Staphylococcus
      aureus (MRSA) using a stepwise infection control strategy that includes an
      avoidance of antimicrobial prophylaxis (AMP) based on surgical wound
      classification and an improvement in operative procedures in gasless single-port
      urologic surgery. METHODS: The study was conducted at an 801-bed university
      hospital. Since 2001, in the urology ward, we have introduced the stepwise
      infection control strategy. In 2007, surveillance cultures for MRSA in all
      urological patients were commenced. The annual incidence of MRSA was calculated
      as a total number of newly identified MRSA cases per 1,000 patient days. Trend
      analysis was performed using a Poisson regression. RESULTS: Over the study
      period, 139,866 patients, including 10,201 urology patients, were admitted to our
      hospital. Of these patients, 3,719 patients, including 134 ones in the urology
      ward, were diagnosed with MRSA throughout the entire hospital. Although the
      incidence of MRSA increased throughout the entire hospital (p = 0.002), it
      decreased significantly in the urology ward (p < 0.0001). Of the 134 cases, 45
      (33.6%) were classified as "imported," and 89 (66.4%) as "acquired." In the
      urology ward, the incidence of acquired MRSA decreased significantly over time (p
      < 0.0001), whereas the incidence of imported MRSA did not change over time (p =
      0.66). A significant decrease (p < 0.0001) in the incidence of clinically
      significant MRSA infection over time was found. CONCLUSIONS: Stepwise infection
      control strategy that includes a reduction or avoidance of antimicrobial
      prophylaxis in minimally invasive surgery can contribute to a reduction in
      hospital-acquired MRSA. TRIAL REGISTRATION: Current study has approved by the
      institutional ethical review board (No.1141).

PMID- 23866942
TI  - The association of Abeta amyloid and composite cognitive measures in healthy
      older adults and MCI.
AB  - BACKGROUND: To date evidence of the relationship between cognition and Abeta
      amyloid during the early stages of Alzheimer's Disease (AD) has been
      inconsistent. This study aimed to describe the nature and magnitude of the
      relationship between Abeta amyloid and cognitive performance of individuals
      without dementia. METHODS: Composite cognitive measures were developed from the
      Australian Imaging Biomarkers and Lifestyle study neuropsychological test battery
      using data from 768 healthy older adults and 133 adults with mild cognitive
      impairment (MCI). A subgroup of this sample (174 healthy, 53 MCI) underwent
      neuroimaging for Abeta amyloid. RESULTS: Within the MCI group individuals with
      high Abeta amyloid showed selective impairment for memory compared with those
      with low Abeta amyloid; however, this difference was not evident in the healthy
      group. CONCLUSIONS: The current findings provide further evidence of the
      relationship between Abeta amyloid and cognition, with memory impairment being
      the primary symptom of the underlying disease during the prodromal phases of AD.

PMID- 23866943
TI  - A biomonitoring study on blood levels of beta-hexachlorocyclohexane among people
      living close to an industrial area.
AB  - BACKGROUND: A chemical plant manufacturing pesticides has been operating since
      the 1950's in the Sacco River Valley (Central Italy). In 2005, high beta
      hexachlorocyclohexane (Beta-HCH) concentrations were found in milk of cows raised
      and fed near the river. We report the results of a biomonitoring study conducted
      in this region to evaluate the body burden of Beta-HCH and to identify the
      determinants of the human contamination. METHODS: We defined four residential
      areas by their distance from the chemical plant and the river, and selected a
      stratified random sample of 626 people aged 25-64 years. We evaluated the
      association, in terms of the geometric mean ratio (GMR), between several
      potential determinants and Beta-HCH serum concentrations using multivariate
      linear regression analysis. RESULTS: Two hundred forty-six serum samples were
      analysed to assess Beta-HCH levels (mean concentration: 99 ng/g lipid; Standard
      Deviation: 121; Geometric Mean: 60.6; Geometric Standard Deviation: 2.65). We
      found a strong association between Beta-HCH and living in the area close to the
      river (GMR: 2.00; 95%CI: 1.36-2.94). Beta-HCH levels were also associated with
      age, level of education, use of private wells and consumption of local food.
      CONCLUSIONS: The results suggest that people living close to the river may have
      been contaminated by Beta-HCH, most likely through water from private wells and
      privately grown food. A programme of epidemiological and clinical surveillance is
      on-going on this population.

PMID- 23866944
TI  - High sensitivity of middle-wavelength infrared photodetectors based on an
      individual InSb nanowire.
AB  - Single-crystal indium antimony (InSb) nanowire was fabricated into middle
      infrared photodetectors based on a metal-semiconductor-metal (M-S-M) structure.
      The InSb nanowires were synthesized using an electrochemical method at room
      temperature. The characteristics of the FET reveal an electron concentration of
      3.6 * 1017 cm-3 and an electron mobility of 215.25 cm2 V-1 s-1. The
      photodetectors exhibit good photoconductive performance, excellent stability,
      reproducibility, superior responsivity (8.4 * 104 A W-1), and quantum efficiency
      (1.96 * 106%). These superior properties are attributed to the high surface-to
      volume ratio and single-crystal 1D nanostructure of photodetectors that
      significantly reduce the scattering, trapping, and the transit time between the
      electrodes during the transport process. Furthermore, the M-S-M structure can
      effectively enhance space charge effect by the formation of the Schottky
      contacts, which significantly assists with the electron injection and
      photocurrent gain. 

PMID- 23866945
TI  - Effect of polyoxyethylene and polyoxypropylene nonionic block copolymers on
      performance and recruitment of immune cell subsets in weaned pigs.
AB  - BACKGROUND: Because European-wide directives are restricting the non-clinical use
      of antibiotics as in-feed growth promotors in swine production, there is an
      intensive search for alternative strategies for control and prevention of losses
      among young pigs. With the growing knowledge of the porcine immune system and its
      endogenous modulation, it has been clearly established that exogenous
      immunomodulation using adjuvants and immune response modifiers (IRMs) represents
      an important prophylactic/therapeutic approach in the prevention/treatment of
      both stress- and microbial-induced disorders that accompaning weaning. However,
      it is essential to select a fully evaluated agent which may act either as a
      nonspecific IRM or synergistically as an adjuvant with vaccines. The synthetic
      macromolecules with a long history as adjuvant and IRM are nonionic block
      copolymers which consist of polyoxyethylene (POE) and polyoxypropylene (POP)
      molecules. METHODS: The aim of this work was to evaluate the effectiveness of POE
      POP given as a single peroral dose on productivity parameters such as body weight
      gain, feed intake and feed conversion ratio, and systemic and intestinal immune
      parameters by assessing the proportions of CD45+ lymphoid cells, CD4+ and CD8+ T
      cells, and CD21+ B cells in the peripheral blood as well as the number of CD45RA+
      naive lymphoid cells residing in the ileal mucosa in weaned pigs during a follow
      up study 5 weeks after the treatment. RESULTS: Pigs treated with POE-POP had
      better feed intake (+ 14.57%), higher average body mass at the end of the
      experiment (20.91 kg vs. 17.61 kg), and higher body weight gain in relation to
      Day 0 (191.63% vs. 144.58%) as well as in relation to nontreated pigs (+ 18.74%),
      with a lower feed conversion ratio (- 30.26%) in comparison to the control pigs.
      A much lower diarrhea severity score (5 vs. 54) was recorded in pigs treated with
      POE-POP (- 90.74%) than in the control pigs. A higher average diarrhea severity
      (ADS) was recorded in the control pigs (1.54 vs. 0.14), whereas the treatmant
      group had much a lower ADS ratio (- 90.91%) after 35 days of the experiment. The
      pigs that were treated with POE-POP had an increased proportion of CD45+, CD4+
      and CD8+ cells at Day 21 (at p < 0.05, p < 0.05 or p < 0.01, respectively), Day
      28 (at p < 0.01, respectively) and Day 35 (at p < 0.01, p < 0.05 or p < 0.01,
      respectively) as well as of CD21+ cells at Day 28 (p < 0.05) and Day 35 of the
      experiment (p < 0.01). Also, these pigs had more numerous CD45RA+ cells in
      interfollicular (p < 0.05) and follicular areas (p < 0.01) of the ileal Peyer's
      patches than did control pigs. CONCLUSION: This property of POE-POP to induce
      recruitment of circulating and intestinal immune cell subsets in weaned pigs may
      allow the use of IRM-active block copolymers as adjuvants for vaccines,
      particularly those orally delivered and targeted to the gut-associated lymphoid
      tissues that are well known to promote rather tolerogenic than protective immune
      responses.

PMID- 23866947
TI  - Survival of our species.

PMID- 23866948
TI  - Exposed bone in bisphosphonate-related osteonecrosis of the jaws may be induced
      and maintained by localized microbial biofilm osteomyelitis.

PMID- 23866946
TI  - Expression of Wnt and TGF-beta pathway components and key adrenal transcription
      factors in adrenocortical tumors: association to carcinoma aggressiveness.
AB  - Factors controlling benign and malignant adrenocortical tumorigenesis are largely
      unknown, but several mouse models suggest an important role for inhibin-alpha
      (INHA). To show that findings in the mouse are relevant to human tumors and
      clinical outcome, we investigated the expression of signaling proteins and
      transcription factors involved in the regulation of INHA in human tumor samples?
      Thirty-one adrenocortical tumor samples, including 13 adrenocortical carcinomas
      (ACCs), were categorized according to Weiss score, hormonal profile, and patient
      survival data and analyzed using immunohistochemistry and RT-PCR. Expression of
      the TGF-beta signaling mediator SMAD3 varied inversely with Weiss score, so that
      SMAD3 expression was lowest in the most malignant tumors. By contrast, SMAD2
      expression was upregulated in most malignant tumors. Wnt pathway co-receptors
      LRP5 and LRP6 were predominantly expressed in benign adrenocortical tumors. In
      ACCs, expression of transcription factors GATA-6 and SF-1 correlated with that of
      their target gene INHA. Moreover, the diminished expression of GATA-6 and SF-1 in
      ACCs correlated with poor outcome. We conclude that the factors driving INHA
      expression are reduced in ACCs with poor outcome, implicating a role for INHA as
      a tumor suppressor in humans. 

PMID- 23866949
TI  - Historical review: First facial pain patient admitted to Massachusetts General
      Hospital, February 1823 and first case series.
AB  - Founded in 1811, the Massachusetts General Hospital recently celebrated its
      bicentennial. The War of 1812 delayed construction of the building so the first
      patient actually was admitted to the hospital 10 years later, on September 3,
      1821. By 1823, the 60 hospital beds were full. Patient 66 was admitted on
      February 28, 1823, and his hospital course, as described in the admissions book,
      was transcribed for the Massachusetts General Hospital bicentennial celebration.
      That case history is reproduced and a case series of 6 similar patients published
      in 1828 by Dr John Warren, surgeon-in-chief and a founder of the hospital, is
      presented. In this report, the authors comment on the diagnosis, treatment, and
      outcome of these patients in the context of the contemporaneous health care
      environment and in light of the current knowledge of facial pain disorders. This
      article was adapted from the authors' commentary for the bicentennial
      celebration. 

PMID- 23866950
TI  - Three-dimensional plotting and printing of an implant drilling guide: simplifying
      guided implant surgery.
AB  - PURPOSE: To present an efficient workflow for the production of implant drilling
      guides using virtual planning tools. For this purpose, laser surface scanning,
      cone beam computed tomography, computer-aided design and manufacturing, and 3
      dimensional (3D) printing were combined. MATERIALS AND METHODS: Intraoral optical
      impressions (iTero, Align Technologies, Santa Clara, CA) and digital 3D
      radiographs (cone beam computed tomography) were performed at the first
      consultation of 1 exemplary patient. With image processing techniques, the
      intraoral surface data, acquired using an intraoral scanner, and radiologic 3D
      data were fused. The virtual implant planning process (using virtual library
      teeth) and the in-office production of the implant drilling guide was performed
      after only 1 clinical consultation of the patient. Implant surgery with a
      computer-aided design and manufacturing produced implant drilling guide was
      performed during the second consultation. The production of a scan prosthesis and
      multiple preoperative consultations of the patient were unnecessary. CONCLUSIONS:
      The presented procedure offers another step in facilitating the production of
      drilling guides in dental implantology. Four main advantages are realized with
      this procedure. First, no additional scan prosthesis is needed. Second, data
      acquisition can be performed during the first consultation. Third, the virtual
      planning is directly transferred to the drilling guide without a loss of
      accuracy. Finally, the treatment cost and time required are reduced with this
      facilitated production process.

PMID- 23866951
TI  - Palatal sinus elevation revisited: a technical note.
AB  - The palatal sinus lift is a good choice for patients with scarred buccal soft
      tissue and those with poor wound healing such as smokers or diabetics or when
      visual side effects such as swelling must be concealed. We provide a surgical
      protocol for palatal sinus lifting without a vertical release incision. The
      incision is started in a slightly palatal aspect, at the distal end of the dental
      arch, and describes a curve laterally on the alveolar crest while running in a
      mesial direction. As a marginal incision, it can continue to the central incisor.
      Submucosal exposure will lift the gum and the greater palatine artery. After
      insertion of a tongue depressor, the sinus is opened on the palatal side,
      opposite the zygomaticoalveolar crest, using a rose bur or a piezotome. After
      sinus augmentation, the incision is easy to close, and the wound will heal
      smoothly. 

PMID- 23866952
TI  - Distraction osteogenesis following low-dose hyperfractionated irradiation in the
      rat mandible.
AB  - PURPOSE: The investigators hypothesized that low-dose hyperfractionated radiation
      would impair mandibular distraction osteogenesis (DO) in a murine mandibular
      model. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent fractionated
      radiation (30 Gy) of the left mandible. After a 2-week recovery period, an
      external frame distractor was applied and gradual distraction of the mandible was
      performed. Tissue was harvested after a 28-day consolidation period. Gross,
      radiologic, and histologic evaluations were undertaken. Control animals underwent
      surgery for an identical time frame without preoperative radiation. RESULTS:
      Animals subjected to preoperative radiation (n = 10) showed suboptimal bone
      formation, including bone atrophy, incomplete bridging of the distraction gap,
      and gross bony defects or nonunion, compared with controls (n = 10). Although
      physical lengthening was achieved, irradiation consistently led to a detrimental
      effect on the normal process of DO. CONCLUSION: This set of experiments
      establishes a valuable rodent model to evaluate the effects of radiation on DO
      and may help to formulate strategies to optimize DO before it is widely applied
      in oncologic reconstruction.

PMID- 23866953
TI  - Surgical management of auricular defect depending on the size, location, and
      tissue involved.
AB  - PURPOSE: Auricular reconstruction is a challenging surgical intervention that
      requires perfect surgical skills, exact planning, and esthetic knowledge. It is
      necessary to use a suitable method of reconstruction for each patient. From 10
      years of experience, the authors have developed a general concept for auricular
      reconstruction. PATIENTS AND METHODS: Seventy-five patients (62 male, 13 female;
      age range, 8 to 92 yr; mean age, 65.9 yr) underwent partial to total auricular
      reconstruction. Tissue loss occurred from different causes: 19 cases of squamous
      cell carcinoma (25.3%), 18 cases of basal cell carcinoma (24%), 14 cases of Bowen
      disease (18.7), 11 cases of malignant melanoma (14.7%), 7 cases of trauma (9.3%),
      3 different malignant tumors (4%), and 3 cases of congenital deformity (4%).
      RESULTS: Defects smaller than one fourth the vertical auricular size (15 to 20
      mm) could be treated by primary closure. A larger defect closed by this method
      caused visible deformity. In defects larger than one to three fourths the
      vertical auricular size (40 to 55 mm), a reversed retroauricular flap was used
      successfully if there was no contraindication or rejection. This flap can be
      combined with other flaps, depending on the flap location, size, and tissue
      involved. In defects exceeding three fourths the vertical auricular size, an
      implant-retained prosthesis was preferred. CONCLUSION: The location and size of a
      defect, the medical condition of the patient, and the desired esthetic outcome
      play an important role in choosing the appropriate method. According to the
      authors' experience, the only contraindications for the reversed retroauricular
      flap are medical condition, poor prognosis, and patient refusal.

PMID- 23866954
TI  - Oromandibular reconstruction using 3D planned triple template method.
AB  - PURPOSE: Reconstruction of an oromandibular defect remains one of the most
      formidable surgical challenges faced by the reconstructive head and neck surgeon.
      The purpose of this study was to illustrate the added value of 3D imaging and
      planning in oromandibular reconstruction. MATERIALS AND METHODS: A 41-year-old
      dentate male patient with T2N0M0 osteosarcoma of the mandible required segmental
      resection of the lateral mandible. In a virtual environment, the bony resection
      and reconstruction were planned preoperatively based on computed tomographic data
      of the head and neck and lower leg. Three custom-made templates designed in a
      computer-assisted design and manufacturing software package and materialized by a
      selective laser sintering process (DuraForm PA, 3D Worknet, Ede, Netherlands)
      were used to transfer this planning to the operating theater. RESULTS: During the
      operative procedure, the 3 templates allowed for a rapid and accurate execution
      of the different surgical steps, ie, establishing the bony surgical margins and
      resection of the mandible (first template), cutting of the fibula while being
      pedicled to the leg (second template), and placement of the fibula to the donor
      site (third template). CONCLUSION: Computer-aided surgery and planning using the
      3-template method lead to an accurate and oncologically safe reconstruction of
      the mandibular geometry by eliminating intraoperative decision making, shortening
      ischemic time of the fibular graft, and shortening overall operative time.

PMID- 23866955
TI  - Long-term survival of a patient with primary small cell neuroendocrine carcinoma
      of the maxillary sinus: a case report.
AB  - Small cell neuroendocrine carcinoma (SNEC) of the paranasal sinuses is an
      extremely rare and distinctive tumor with aggressive clinical behavior. Moreover,
      SNECs originating in the head and neck region have been reported to be highly
      aggressive and to have a poor prognosis. This report describes a patient with a
      maxillary sinus SNEC who was successfully treated with induction chemotherapy
      using cisplatin and etoposide followed by concurrent chemoradiation therapy with
      cisplatin and etoposide as radiosensitizers. The patient has remained free of
      recurrence during 7 years of follow-up. To the authors' knowledge, this is the
      first case report describing long-term survival in a patient with a resolved
      primary SNEC of the maxilla that was successfully treated with neoadjuvant
      chemotherapy and concurrent chemoradiotherapy. The clinical and pathologic
      features of the tumor and the optimal treatment of this patient are discussed. 

PMID- 23866956
TI  - Intermittent androgen deprivation therapy: clarity from confusion.

PMID- 23866957
TI  - Managing hereditary angioedema patients undergoing otolaryngeal procedures.
AB  - BACKGROUND: Hereditary angioedema (HAE), a rare autosomal dominant disorder, is
      characterized by repeated attacks of swelling of the skin, gastrointestinal
      tract, face, larynx, and other organs. In most cases it is caused by low levels
      of functional C1 esterase inhibitor (C1-INH), a serine protease inhibitor that
      plays important regulatory roles in the complement, contact, and fibrinolytic
      pathways. METHODS: Lack of functional C1-INH results in excessive release of
      bradykinin, which triggers vasodilation, vascular permeability, and edema. Most
      attacks are mild and self-limiting, but untreated laryngeal attacks may cause
      rapid asphyxiation and death. Potential triggers of laryngeal attacks include
      trauma to or manipulation of the face, mouth, or upper airway. Therefore, before
      performing such a procedure in a patient with HAE, the otolaryngologist should
      consult with the patient, the physician managing the HAE, and the
      anesthesiologist and make appropriate preparations for prevention and/or
      treatment of an attack. RESULTS: Current World Allergy Organization and European
      guidelines recommend the use of i.v. plasma-derived C1-INH replacement for short
      term prophylaxis of angioedema attacks. Other effective options include danazol
      given for several days before and after the procedure and fresh-frozen plasma,
      but these may not be as effective as C1-INH and may be associated with a high
      rate of adverse events. CONCLUSION: Acute attacks, which may occur many hours
      after a procedure, may be treated with C1-INH; icatibant, a bradykinin B2
      receptor antagonist; or ecallantide, a kallikrein inhibitor, all of which have
      been shown to reduce the duration and severity of HAE attacks.

PMID- 23866958
TI  - Anti-Wolbachia drug discovery and development: safe macrofilaricides for
      onchocerciasis and lymphatic filariasis.
AB  - Anti-Wolbachia therapy delivers safe macrofilaricidal activity with superior
      therapeutic outcomes compared to all standard anti-filarial treatments, with the
      added benefit of substantial improvements in clinical pathology. These outcomes
      can be achieved, in principle, with existing registered drugs, e.g. doxycycline,
      that are affordable, available to endemic communities and have well known, albeit
      population-limiting, safety profiles. The key barriers to using doxycycline as an
      mass drug administration (MDA) strategy for widespread community-based control
      are the logistics of a relatively lengthy course of treatment (4-6 weeks) and
      contraindications in children under eight years and pregnancy. Therefore, the
      primary goal of the anti-Wolbachia (A.WOL) consortium is to find drugs and
      regimens that reduce the period of treatment from weeks to days (7 days or less),
      and to find drugs which would be safe in excluded target populations (pregnancy
      and children). A secondary goal is to refine regimens of existing antibiotics
      suitable for a more restricted use, prior to the availability of a regimen that
      is compatible with MDA usage. For example, for use in the event of the emergence
      of drug-resistance, in individuals with high loiasis co-infection and at risk of
      severe adverse events (SAE) to ivermectin, or in post-MDA 'endgame scenarios',
      where test and treat strategies become more cost effective and deliverable.

PMID- 23866959
TI  - Understanding loneliness during adolescence: developmental changes that increase
      the risk of perceived social isolation.
AB  - Loneliness is typically defined in terms of feeling states. In this review, we
      take a somewhat different approach, describing loneliness in terms of perceived
      social isolation. Vulnerabilities to perceived social isolation differ across the
      lifespan. Unique properties of adolescence are identified that carry special risk
      for perceived social isolation. These include (but are not limited to)
      developmental changes in companions, developmental changes in autonomy and
      individuation, identity exploration, cognitive maturation, developmental changes
      in social perspective taking, and physical maturation. Scholars are encouraged to
      consider loneliness through the lens of perceived social isolation so as to
      better understand how the experience of physical isolation varies across
      adolescence. 

PMID- 23866960
TI  - Histopathological and clinical evaluation of Kombucha tea and Nitrofurazone on
      cutaneous full-thickness wounds healing in rats: an experimental study.
AB  - BACKGROUND: Kombucha, a fermented tea (KT) is claimed to possess many beneficial
      properties. The aim of this study was to evaluate clinical and histopathological
      alterations of Kombucha tea and Nitrofurazone on cutaneous full-thickness wounds
      healing in rat. METHODS: In present study 24 Wister -albino rats weighing 150-200
      g were selected and divided to two treatment groups as Nitrofurazone ointment
      (0.2%) and Kombucha tea. Subsequently, the anesthesia was exerted by Ketamin
      hydrochloride 10% (40 mg/kg) and Xylasine (2 mg/kg) through intra muscular (IM)
      route. Furthermore, upon preparation of dorsal region of the animal for surgery,
      a piece of full-thickness skin removed (2 * 2 cm). In order to comparing wounds
      healing clinically and histologically, once every four days from the
      commencement, the wounds were photographed and the healed surface was measured by
      Scion image software. RESULT: The clinical findings indicated that the Kombucha
      fungus resulted in precipitating healing than Nitrofurazone; however, it was not
      significant (p > 0.05). In order to pathological comparing of wound healing
      process, several wound biopsies were taken on 4, 8, 12, 16 and 20th days.
      Additionally, the histopathological results demonstrated that there was
      inflammation in Nitrofurazone group through twelveth day, somehow the epithelium
      was formed and abundant vessels were visible. Although on 16th day and the
      previous days the healing condition of Kombucha fungus was considered as minimal
      rate, revealing it is similar to Nitrofurazone group on 20th day. CONCLUSIONS: To
      wrap up. These observations suggest that the Kombucha fungus healing quality was
      rapid from 12th day to the end of the research, whereas no significant difference
      was observed. VIRTUAL SLIDE: The virtual slide(s) for this article can be found
      here: http://www.diagnosticpathology.diagnomx.eu/vs/1107407136102196.

PMID- 23866961
TI  - Methyl-beta-cyclodextrin alters adipokine gene expression and glucose metabolism
      in swine adipose tissue.
AB  - This study was designed to determine whether methyl-beta-cyclodextrin (MCD) can
      substitute for albumin in incubation medium for neonatal swine adipose tissue
      explants, or whether MCD affects metabolism and cytokine expression. Subcutaneous
      adipose tissue explants (100 +/- 10 mg) were prepared from 21-day-old pigs.
      Explants were incubated in medium 199 supplemented with 25 mM HEPES, 1.0 nM
      insulin at 37 degrees C. The medium also contained bovine serum albumin (BSA) or
      MCD at 0%, 0.05%, 0.1%, 0.2% or 0.3%. Tissue explants were treated with these
      media for 1 h and then switched to the same basal incubation medium containing
      0.05% BSA. Explants were removed from basal medium at 2 or 8 h of incubation, and
      real-time PCR was performed to assess expression of tumor necrosis alpha (TNF)
      and interleukin 6 (IL6), acetyl CoA carboxylase (ACAC) and fatty acid synthase
      (FASN). Alternatively, rates of 14C-glucose oxidation and lipogenesis were
      monitored +/- insulin (100 nM), following MCD treatment. Incubation with BSA had
      minimal effects on gene expression or adipose tissue metabolism, only producing a
      doubling in TNF mRNA abundance (P < 0.01). Treatment with MCD increased TNF mRNA
      abundance by eightfold (P < 0.009), whereas IL6 gene expression increased a 100
      fold (P < 0.001) with a suppression in ACAC and FASN expression (P < 0.01). This
      was paralleled by MCD inhibition of insulin-stimulated glucose oxidation and
      lipogenesis (P < 0.001). Addition of a TNF antibody to the incubation medium
      alleviated this inhibition of insulin-stimulated glucose metabolism by ~30% (P <
      0.05).

PMID- 23866962
TI  - Does use of a virtual environment change reaching while standing in patients with
      traumatic brain injury?
AB  - BACKGROUND: Although numerous virtual reality applications have been developed
      for sensorimotor retraining in neurologically impaired individuals, it is unclear
      whether the virtual environment (VE) changes motor performance, especially in
      patients with brain injuries. To address this question, the movement
      characteristics of forward arm reaches during standing were compared in physical
      and virtual environments, presented at different viewing angles. METHODS: Fifteen
      patients with traumatic brain injuries (TBI) and 15 sex- and age-matched healthy
      individuals performed virtual reaches in a computer-generated courtyard with a
      flower-topped hedge. The hedge was projected on a flat screen and viewed in 3D
      format in 1 of 3 angles: 10 degrees  above horizon (resembling a real-world
      viewing angle), 50 degrees  above horizon, or 90 degrees  above horizon (directly
      overhead). Participants were instructed to reach with their dominant hand avatar
      and to touch the farthest flower possible without losing their balance or
      stepping. Virtual reaches were compared with reaches-to-point to a target in an
      equivalent physical environment. A set of kinematic parameters was used. RESULTS:
      Reaches by patients with TBI were characterized by shorter distances, lower peak
      velocities, and smaller postural displacements than reaches by control
      individuals. All participants reached ~9% farther in the VE presented at a 50
      degrees  angle than they did in the physical environment. Arm displacement in the
      more natural 10 degrees  angle VE was reduced by the same 9-10% compared to
      physical reaches. Virtual reaches had smaller velocity peaks and took longer than
      physical reaches. CONCLUSION: The results suggest that visual perception in the
      VE differs from real-world perception and the performance of functional tasks
      (e.g., reaching while standing) can be changed in TBI patients, depending on the
      viewing angle. Accordingly, the viewing angle is a critical parameter that should
      be adjusted carefully to achieve maximal therapeutic effect during practice in
      the VE.

PMID- 23866963
TI  - Face blindness and person misidentification in non-scientific parlance.

PMID- 23866964
TI  - Histone deacetylase inhibitor potentiated the ability of MTOR inhibitor to induce
      autophagic cell death in Burkitt leukemia/lymphoma.
AB  - BACKGROUND: Burkitt leukemia/lymphoma is a major subtype of aggressive B-cell
      lymphoma. Biological targeted therapies on this disease need to be further
      investigated and may help to improve the clinical outcome of the patients.
      METHODS: This study examined the anti-tumor activity of the histone deacetylases
      (HDAC) inhibitor valproic acid (VPA) combined with the mammalian target of
      rapamycin (MTOR) inhibitor temsirolimus in Burkitt leukemia/lymphoma cell lines,
      as well as in primary tumor cells and a murine xenograft model. RESULTS: Co
      treatment of VPA and temsirolimus synergistically inhibited the tumor cell growth
      and triggered the autophagic cell death, with a significant inhibition of MTOR
      signaling and MYC oncoprotein. Functioned as a class I HDAC inhibitor, VPA
      potentiated the effect of temsirolimus on autophagy through inhibiting HDAC1.
      Molecular silencing of HDAC1 using small interfering RNA (siRNA) attenuated VPA
      mediated regulation of CDKN1A, CDKN1B and LC3-I/II, regression of tumor cell
      growth and induction of autophagy. Meanwhile, VPA counteracted temsirolimus
      induced AKT activation via HDAC3 inhibition. HDAC3 siRNA abrogated the ability of
      VPA to modulate AKT phosphorylation, to suppress tumor cell growth and to induce
      autophagy. Strong antitumor effect was also observed on primary tumor cells while
      sparing normal hematopoiesis ex vivo. In a murine xenograft model established
      with subcutaneous injection of Namalwa cells, dual treatment efficiently blocked
      tumor growth, inhibited MYC and induced in situ autophagy. CONCLUSIONS: These
      findings confirmed the synergistic effect of the HDAC and MTOR inhibitors on
      Burkitt leukemia/lymphoma, and provided an insight into clinical application of
      targeting autophagy in treating MYC-associated lymphoid malignancies.

PMID- 23866965
TI  - Extracorporeal tumor cell filtration during extended liver surgery: first
      clinical use of leukocyte depletion filters--case series.
AB  - BACKGROUND: During oncologic surgery, intraoperative manipulation of tumor tissue
      is almost unpreventable and causes a high risk of tumor cell dissemination into
      venous blood. A tumor cell-reducing effect of leukocyte adhesion filter systems
      has been shown under in vitro conditions. METHODS: In a first clinical attempt,
      leukocyte adhesion filters were integrated into veno-venous bypass systems in
      four patients undergoing extended liver surgery for secondary hepatic
      malignancies.Practicability, handling, and safety aspects as well as potency of
      cell removal and clinical side effects of the filter system were analyzed.
      RESULTS: All patients tolerated the application of the system without problems
      during operative and postoperative follow-up. Immunohistochemical staining of
      perioperative blood samples detected cytokeratin positive (CK+) cells in three
      cases during the hepatic mobilization. CONCLUSIONS: Effectiveness of CK+ cell
      depletion and safety of the procedure was shown. The presented surgical technique
      represents a safe and innovative tool; however, clinical significance has to be
      examined in a larger patient cohort.

PMID- 23866966
TI  - [Acute cellular rejection in a liver transplantation patient due to changing the
      brand of a generic immunosuppressant].

PMID- 23866967
TI  - OPAA template-directed synthesis and optical properties of metal nanocrystals.
AB  - Ag and Cu nanocrystals (NCs) were assembled into ordered porous anodic alumina
      (OPAA) by a single-potential-step chronoamperometry technique. The composition,
      morphology, microstructure, and optical property were analyzed by X-ray
      diffraction, field-emission scanning electron microscopy, transmission electron
      microscopy, selected area electron diffraction, and optical absorption
      spectroscopy. The results indicate that metallic NCs/OPAA composite possesses a
      significant surface plasmon resonance absorption. For continuous
      electrodeposition, metallic nanowires are smooth and uniform with face-centered
      cubic (fcc) single-crystalline structure; however, for interval
      electrodeposition, the nanowires are bamboo-like or pearl-chain-like with fcc
      polycrystalline structure. The length of the nanoparticle nanowires or the single
      crystalline nanowires can be controlled well by adjusting the experimental cycle
      times or the continuous depositing time. The transverse dipole resonance of
      metallic NCs enhances and displays a blue shift with increasing electrodeposition
      time or experimental cycle times, which is consistent with Zong's results but
      contradictory to Duan's results. The formation mechanisms of the nanoparticle
      nanowires and the single-crystalline nanowires were discussed in detail. 

PMID- 23866968
TI  - The role of a student-run clinic in providing primary care for Calgary's homeless
      populations: a qualitative study.
AB  - BACKGROUND: Despite the increasing popularity of Student-Run Clinics (SRCs) in
      Canada, there is little existing literature exploring their role within the
      Canadian healthcare system. Generalizing American literature to Canadian SRCs is
      inappropriate, given significant differences in healthcare delivery between the
      two countries. Medical students at the University of Calgary started a SRC
      serving Calgary's homeless population at the Calgary Drop-In and Rehabilitation
      Centre (CDIRC). This study explored stakeholders' desired role for a SRC within
      Calgary's primary healthcare system and potential barriers it may face. METHODS:
      Individual and group semi-structured interviews were undertaken with key
      stakeholders in the SRC project: clients (potential patients), CDIRC staff, staff
      from other stakeholder organizations, medical students, and faculty members.
      Convenience sampling was used in the recruitment of client participants.
      Interview transcripts were analyzed using a coding template which was derived
      from the literature. RESULTS: Participants identified factors related to the
      clinic and to medical students that suggest there is an important role for a SRC
      in Calgary. The clinic was cited as improving access to primary healthcare for
      individuals experiencing homelessness. It was suggested that students may be
      ideally suited to provide empathetic healthcare to this population. Barriers to
      success were identified, including continuity of care and the exclusion of some
      subsets of the homeless population due to location. CONCLUSIONS: SRCs possess
      several unique features that may make them a potentially important primary
      healthcare resource for the homeless. Participants identified numerous benefits
      of the SRC to providing primary care for homeless individuals, as well as several
      important limitations that need to be accounted for when designing and
      implementing such a program.

PMID- 23866969
TI  - [New clinical perspectives in the management of oral direct anticoagulant
      agents].

PMID- 23866970
TI  - Implementing a new EPR lineshape parameter for organic radicals in carbonaceous
      matter.
AB  - BACKGROUND: Electron Paramagnetic Resonance (EPR) is a non-destructive, non
      invasive technique useful for the characterization of organic moieties in
      primitive carbonaceous matter related to the origin of life. The classical EPR
      parameters are the peak-to-peak amplitude, the linewidth and the g factor;
      however, such parameters turn out not to suffice to fully determine a single EPR
      line. RESULTS: In this paper, we give the definition and practical implementation
      of a new EPR parameter based on the signal shape that we call the R10 factor.
      This parameter was originally defined in the case of a single symmetric EPR line
      and used as a new datation method for organic matter in the field of exobiology.
      CONCLUSION: Combined to classical EPR parameters, the proposed shape parameter
      provides a full description of an EPR spectrum and opens the way to novel
      applications like datation. Such a parameter is a powerful tool for future EPR
      studies, not only of carbonaceous matter, but also of any substance which
      spectrum exhibits a single symmetric line. REPRODUCIBILITY: The paper is a
      literate program-written using Noweb within the Org-mode as provided by the Emacs
      editor- and it also describes the full data analysis pipeline that computes the
      R10 on a real EPR spectrum.

PMID- 23866972
TI  - An unusual cause of refractory persistent pulmonary hypertension of the newborn:
      anomalous origin of one pulmonary artery.
AB  - Persistent pulmonary hypertension of the newborn is a source of considerable
      mortality and morbidity. Anomalous origin of one pulmonary artery, an uncommon
      congenital cardiac malformation, is a rare cause of persistent pulmonary
      hypertension. Here, we report the case of a patient with an anomalous origin of
      one pulmonary artery from the innominate artery who presented with persistent
      pulmonary hypertension refractory to treatment. 

PMID- 23866971
TI  - Association between In Utero arsenic exposure, placental gene expression, and
      infant birth weight: a US birth cohort study.
AB  - BACKGROUND: Epidemiologic studies and animal models suggest that in utero arsenic
      exposure affects fetal health, with a negative association between maternal
      arsenic ingestion and infant birth weight often observed. However, the molecular
      mechanisms for this association remain elusive. In the present study, we aimed to
      increase our understanding of the impact of low-dose arsenic exposure on fetal
      health by identifying possible arsenic-associated fetal tissue biomarkers in a
      cohort of pregnant women exposed to arsenic at low levels. METHODS: Arsenic
      concentrations were determined from the urine samples of a cohort of 133 pregnant
      women from New Hampshire. Placental tissue samples collected from enrollees were
      homogenized and profiled for gene expression across a panel of candidate genes,
      including known arsenic regulated targets and genes involved in arsenic
      transport, metabolism, or disease susceptibility. Multivariable adjusted linear
      regression models were used to examine the relationship of candidate gene
      expression with arsenic exposure or with birth weight of the baby. RESULTS:
      Placental expression of the arsenic transporter AQP9 was positively associated
      with maternal urinary arsenic levels during pregnancy (coefficient estimate:
      0.25; 95% confidence interval: 0.05 - 0.45). Placental expression of AQP9 related
      to expression of the phospholipase ENPP2 which was positively associated with
      infant birth weight (coefficient estimate: 0.28; 95% CI: 0.09 - 0.47). A
      structural equation model indicated that these genes may mediate arsenic's effect
      on infant birth weight (coefficient estimate: -0.009; 95% confidence interval: 
      0.032 - -0.001; 10,000 replications for bootstrapping). CONCLUSIONS: We
      identified the expression of AQP9 as a potential fetal biomarker for arsenic
      exposure. Further, we identified a positive association between the placental
      expression of phospholipase ENPP2 and infant birth weight. These findings suggest
      a path by which arsenic may affect birth outcomes.

PMID- 23866973
TI  - Detection of human taeniases in Tibetan endemic areas, China.
AB  - Detection of taeniasis carriers of Taenia solium is essential for control of
      cysticercosis in humans and pigs. In the current study, we assessed the positive
      detection rate of a self-detection tool, stool microscopy with direct smear and
      coproPCR for taeniasis carriers in endemic Tibetan areas of northwest Sichuan.
      The self-detection tool through questioning about a history of proglottid
      expulsion within the previous one year showed an overall positive detection rate
      of more than 80% for Taenia saginata, T. solium and T. asiatica. The positive
      detection rate was similar for T. saginata and T. solium. In 132 taeniid tapeworm
      carriers, 68 (51.5%) were detected by microscopy and 92 (69.7%) were diagnosed by
      coproPCR. A combination of microscopy and coproPCR increased the positive
      detection rate to 77.3%. There remained 10 cases (7.6%) coproPCR negative but
      microscopy positive. Due to the high cost and complicated process, coproPCR is
      required for the identification of Taenia species only when necessary, though it
      had a significant higher positive detection rate than microscopy. Combined use of
      self-detection and stool microscopy are recommended in community-based mass
      screening for taeniases in this Tibetan area or in other situation-similar
      endemic regions.

PMID- 23866974
TI  - Probiotics from research to market: the possibilities, risks and challenges.
AB  - Probiotic foods can affect large parts of the population, while therapeutic
      applications have a less wide scope. While commercialization routes and
      regulatory requirements differ for both applications, both will need good
      scientific support. Today, probiotics are mainly used for gastrointestinal
      applications, their use can easily be extended to skin, oral and vaginal health.
      While most probiotics currently belong to food-grade species, the future may
      offer new functional microorganisms in food and pharma. This review discusses the
      crosstalk between probiotic producers, regulatory people, medical care and
      healthcare workers, and the scientific community. 

PMID- 23866975
TI  - Bacteriotherapy for the treatment of intestinal dysbiosis caused by Clostridium
      difficile infection.
AB  - Faecal microbiota transplantation (FMT) has been used for more than five decades
      to treat a variety of intestinal diseases associated with pathological imbalances
      within the resident microbiota, termed dysbiosis. FMT has been particularly
      effective for treating patients with recurrent Clostridium difficile infection
      who are left with few clinical options other than continued antibiotic therapy.
      Our increasing knowledge of the structure and function of the human intestinal
      microbiota and C. difficile pathogenesis has led to the understanding that FMT
      promotes intestinal ecological restoration and highlights the microbiota as a
      viable therapeutic target. However, the use of undefined faecal samples creates a
      barrier for widespread clinical use because of safety and aesthetic issues. An
      emerging concept of bacteriotherapy, the therapeutic use of a defined mixture of
      harmless, health-associated bacteria, holds promise for the treatment of patients
      with severe C. difficile infection, and possibly represents a paradigm shift for
      the treatment of diseases linked to intestinal dysbiosis. 

PMID- 23866976
TI  - The mechanisms of surface chemistry effects of mesoporous silicon nanoparticles
      on immunotoxicity and biocompatibility.
AB  - Despite steadily increasing insights on the biocompatibility of PSi nanoparticles
      (NPs), an extensive biosafety study on the immune and red blood cells (RBCs) is
      still lacking. Herein, we evaluated the impact of the PSi NPs' surface chemistry
      on immune cells and human RBCs both in vitro and in vivo. Negatively charged
      hydrophilic and hydrophobic PSi NPs caused less ATP depletion and genotoxicity
      than the positively charged amine modified hydrophilic PSi NPs, demonstrating the
      main role of PSi NPs' surface charge on the immunocompatibility profile.
      Furthermore, cells with lower metabolic activity, longer doubling time, and
      shorter half-life were more sensitive to the concentration- and time-dependent
      toxicity in the following order: T-cells ~ monocytes > macrophages ~ B-cells. RBC
      hemolysis and imaging assay revealed a significant correlation between the
      surface chemistry, the amount of the PSi NPs adsorbed on the cell surface and the
      extent of morphological changes. The in vivo results showed that despite mild
      renal steatosis, glomerular degeneration, hepatic central vein dilation and white
      pulp shrinkage in spleen, no notable changes were observed in the serum level of
      biochemical and hematological factors. This study is a comprehensive
      demonstration of the mechanistic direct and indirect genotoxicity effects of PSi
      NPs, elucidating the most influencing properties for the PSi NPs' design.

PMID- 23866977
TI  - Spheroid formation of human thyroid cancer cells in an automated culturing system
      during the Shenzhou-8 Space mission.
AB  - Human follicular thyroid cancer cells were cultured in Space to investigate the
      impact of microgravity on 3D growth. For this purpose, we designed and
      constructed a cell container that can endure enhanced physical forces, is
      connected to fluid storage chambers, performs media changes and cell harvesting
      automatically and supports cell viability. The container consists of a cell
      suspension chamber, two reserve tanks for medium and fixative and a pump for
      fluid exchange. The selected materials proved durable, non-cytotoxic, and did not
      inactivate RNAlater. This container was operated automatically during the
      unmanned Shenzhou-8 Space mission. FTC-133 human follicular thyroid cancer cells
      were cultured in Space for 10 days. Culture medium was exchanged after 5 days in
      Space and the cells were fixed after 10 days. The experiment revealed a scaffold
      free formation of extraordinary large three-dimensional aggregates by thyroid
      cancer cells with altered expression of EGF and CTGF genes under real
      microgravity. 

PMID- 23866979
TI  - Effect of detoxified karanja (Pongamia spp.) cake on testicular architecture and
      semen production in ram lambs.
AB  - The protein-rich non-conventional detoxified karanja cake (dKC) can be used in
      place of conventional protein supplements like soybean meal (SBM), groundnut
      meal, etc. in livestock feed. The present study was conducted to assess the
      effect of two levels of dKC by replacing SBM on testicular architecture, semen
      quality and expressions of mRNAs encoding luteinizing hormone receptor (LHR) and
      insulin-like growth factor (IGF-I) in testes of ram lambs. Eighteen ram lambs
      were randomly divided into three groups (n = 6) and fed different levels (%) of
      karanja cake (0% replacement--control; 50% replacement--dKC-50 and 75%
      replacement--dKC-75) for 140 days. After 120 days of feeding, the semen from the
      animals was collected and analysed. The testes samples were collected on day 140
      of feeding for transcripts expression studies. The dKC-50 group had no change in
      BW, whereas dKC-75 group showed decreased (P < 0.05) BW as compared with control.
      The number of animals ejaculated semen in dKC-75 group was lower (P < 0.05) than
      the control group. A reduction (P < 0.05) in LHR expression in dKC-75 was
      observed, whereas a reduction in IGF-I expression (P < 0.05) was observed in dKC
      50 and dKC-75 as compared with control group. The study reveals that in ram
      lambs, long-term feeding of dKC at 50% replacement of SBM may not affect BW.
      However, long-term feeding of dKC as a replacement of SBM may affect testicular
      function.

PMID- 23866978
TI  - Epigenetic regulation of the ribosomal cistron seasonally modulates enrichment of
      H2A.Z and H2A.Zub in response to different environmental inputs in carp (Cyprinus
      carpio).
AB  - BACKGROUND: The specific deposition of histone variants into chromatin is an
      important epigenetic mechanism that contributes to gene regulation through
      chromatin architectural changes. The histone variant H2A.Z is essential in higher
      eukaryotes, and its incorporation within chromatin is a relevant process for gene
      expression and genome stability. However, the dual positive and negative roles of
      H2A.Z in gene regulation still remain unclear. We previously reported that
      acclimatization in common carp fish (Cyprinus carpio) involves cyclical seasonal
      gene reprogramming as an adaptation response to its natural environment, when
      rRNA synthesis and processing are profoundly affected. Epigenetic mechanisms
      primarily contribute to the transcriptional modulation of ribosomal genes
      concomitant with the acclimatization process, thus significantly regulating this
      process. The aim of this study was to describe the presence of several H2A.Z
      subtypes in carp, and assess the role of H2A.Z on the ribosomal cistron in summer
      and winter-acclimatized carp. RESULTS: This paper reports for the first time
      about the transcriptional expression of four different H2A.Z subtypes belonging
      to the same organism. Remarkably, a novel H2A.Z.7 was found, which corresponds to
      a tissue-specific histone subtype that contains seven amino acid residues longer
      than the canonical H2A.Z. Moreover, H2A.Z enrichment through the ribosomal
      cistron was significantly higher during summer, when rRNA transcription and
      processing are highly active, than it was in winter. Similar patterns of H2A.Z
      enrichment are found in two seasonally active promoters for genes transcribed by
      RNA polymerase II, the L41 and Delta9-desaturase genes. Interestingly,
      ubiquitylated-H2A.Z (H2A.Zub) was strongly enriched on regulatory regions of the
      ribosomal cistron in summer-acclimatized carp. Additionally, H2A.Z was present in
      both heterochromatin and euchromatin states on ribosomal cistron and RNA
      polymerase II promoters. CONCLUSIONS: Our study revealed seasonally-dependent
      H2A.Z enrichment for active ribosomal cistron and RNA polymerase II promoters
      during the carp environmental adaptation. Moreover, seasonal H2A.Zub enrichment
      appears as a specific mechanism contributing to the regulation of chromatin
      architecture under natural conditions. The existence of several H2A.Z subtypes in
      carp suggests that the epigenetic regulation in this species constitutes a
      complex and finely tuned mechanism developed to cope with seasonal environmental
      changes that occur in its habitat.

PMID- 23866981
TI  - Adipocytokines in relation to cardiovascular disease.
AB  - Adipose tissue can be considered as a huge gland producing paracrine and
      endocrine hormones, the adipo(cyto)kines. There is growing evidence that these
      adipo(cyto)kines may link obesity to cardiovascular diseases. The excessive
      adipocyte hypertrophy in obesity induces hypoxia in adipose tissue. This leads to
      adiposopathy, the process that converts "healthy" adipose tissue to "sick"
      adipose tissue. This is accompanied by a change in profile of adipo(cyto)kines
      released, with less production of the "healthy" adipo(cyto)kines such as
      adiponectin and omentin and more release of the "unhealthy" adipo(cyto)kines,
      ultimately leading to the development of cardiovascular diseases. The present
      review provides a concise and general overview of the actual concepts of the role
      of adipo(cyto)kines in endothelial dysfunction, hypertension, atherosclerosis and
      heart diseases. The knowledge of these concepts may lead to new tools to improve
      health in the next generations. 

PMID- 23866980
TI  - Acute effects of fructose consumption on uric acid and plasma lipids in patients
      with impaired renal function.
AB  - OBJECTIVE: Metabolic disturbances are common in patients with renal function
      impairment and are related to high rates of cardiovascular incidents and
      mortality. Kidney transplantation leads to improved survival but may lead to
      additional metabolic alterations caused by immunosuppressive drugs and improved
      nutrition. MATERIALS AND METHODS: The short-term effect of oral fructose load on
      serum uric acid (UA), plasma lipids, and blood pressure (BP) was studied in 85
      patients with chronic kidney disease (CKD) and impairment of renal function
      (glomerular filtration rate 50-65 ml/min per 1.73 m(2)), comprising 55 renal
      transplant recipients (RTR) treated with standard triple immunosuppressive
      therapy including a calcineurin inhibitor (CNI) cyclosporine A (CsA) or
      tacrolimus (Tac) and 30 non-transplanted patients with CKD. Both non-transplanted
      CKD patients and RTR had stable renal function and a comparable degree of kidney
      dysfunction. All subjects received orally 70 g of fructose dissolved in 200 ml of
      water. Serum UA, lipids, and blood pressure were measured at baseline and 60,
      120, 180, and 240 minutes after fructose administration. RESULTS: There was a
      significant increase of serum UA concentration (p<0.001) in both CKD patients and
      RTR--CsA- or Tac-treated patients comparable in the latter. Total cholesterol
      (TC), LDL, and HDL cholesterol significantly decreased and serum triglycerides
      (TG) markedly increased in RTR, whereas in CKD patients all serum lipid fractions
      increased. Blood pressure was unaffected by fructose intake. CONCLUSION: Both non
      transplanted and transplanted patients with mild renal function impairment show
      similar acute purine metabolic disturbances following oral administration of
      fructose but in the latter dietary fructose may induce a smaller hyperlipidemic
      response.

PMID- 23866982
TI  - Suppression of atrogin-1 and MuRF1 prevents dexamethasone-induced atrophy of
      cultured myotubes.
AB  - OBJECTIVE: The mechanistic role of the ubiquitin ligases atrogin-1 and MuRF1 in
      glucocorticoid-induced muscle wasting is not fully understood. Here, we tested
      the hypothesis that glucocorticoid-induced muscle atrophy is at least in part
      linked to atrogin-1 and MuRF1 expression and that the ubiquitin ligases are
      regulated by compensatory mechanisms. METHODS: The expression of atrogin-1 and
      MuRF1 was suppressed individually or in combination in cultured L6 myotubes by
      using siRNA technique. Myotubes were treated with dexamethasone followed by
      determination of mRNA and protein levels for atrogin-1 and MuRF1, protein
      synthesis and degradation rates, and myotube morphology. RESULTS: Suppression of
      atrogin-1 resulted in increased expression of MuRF1 and vice versa, suggesting
      that the ubiquitin ligases are regulated by compensatory mechanisms. Simultaneous
      suppression of atrogin-1 and MuRF1 resulted in myotube hypertrophy, mainly
      reflecting stimulated protein synthesis, and prevented dexamethasone-induced
      myotube atrophy, mainly reflecting inhibited protein degradation. CONCLUSIONS:
      The results provide evidence for a link between upregulated atrogin-1 and MuRF1
      expression and glucocorticoid-induced muscle atrophy. The study also suggests
      that atrogin-1 and MuRF1 levels are regulated by compensatory mechanisms and that
      inhibition of both ubiquitin ligases may be needed to prevent glucocorticoid
      induced muscle proteolysis and atrophy.

PMID- 23866983
TI  - The impact of parent socio-economic status on executive functioning and cortical
      morphology in individuals with schizophrenia and healthy controls.
AB  - BACKGROUND: Relatively lower executive functioning is characteristic of
      individuals with schizophrenia. As low socio-economic status (SES) early in life
      (i.e. parent SES) has been linked with lower executive skills in healthy
      children, we hypothesized that parental SES (pSES) would be more strongly related
      to executive functioning in individuals with schizophrenia than in controls and
      have a greater impact on prefrontal cortical morphology. METHOD: Healthy controls
      (n = 125) and individuals with schizophrenia (n = 102) completed tests assessing
      executive functioning and intelligence. The groups were matched on pSES, which
      was evaluated with the Hollingshead-Redlich scale. A principal components
      analysis (PCA) was conducted on 10 variables from six executive tests, yielding
      three specific components (fluency, planning and response inhibition). Voxel
      based morphometry (VBM) was used to evaluate effects of pSES on gray matter (GM)
      concentration. RESULTS: Lower pSES was associated with lower scores across the
      three executive functioning components, and a significant group by pSES
      interaction was observed such that low pSES, in particular, affected individuals
      with schizophrenia. These effects remained significant when intellectual ability,
      education and self-SES (sSES) were added as covariates. VBM revealed that lower
      pSES was associated with reduced GM volume in several anterior brain regions,
      especially the superior frontal gyrus, in patients but not in controls.
      CONCLUSIONS: These findings suggest that individuals with schizophrenia may be
      particularly vulnerable to the adverse impact of low pSES, in terms of both lower
      executive skills and reduced anterior GM volumes.

PMID- 23866984
TI  - Robotic pancreatic surgery is no substitute for experience and clinical judgment:
      an initial experience and literature review.
AB  - Robotic pancreatic surgery offers technical advantages, and has been applied
      across many surgical specialties. We report an initial experience of 12 distal
      pancreatic resections for benign tumors from an established pancreatic center
      with previous general and biliary laparoscopic experience. Of a total of 12
      patients, 7 were women; the mean age was 55.5 years, and the lesions included 8
      distal intraductal papillary mucinous tumors, 1 insulinoma and in 3 a non
      functioning neuroendocrine tumor. All operations were performed in between 90 and
      180 minutes, and blood loss and hospital stay were minimal.

PMID- 23866985
TI  - Operation of a brain-computer interface walking simulator for individuals with
      spinal cord injury.
AB  - BACKGROUND: Spinal cord injury (SCI) can leave the affected individuals with
      paraparesis or paraplegia, thus rendering them unable to ambulate. Since there
      are currently no restorative treatments for this population, novel approaches
      such as brain-controlled prostheses have been sought. Our recent studies show
      that a brain-computer interface (BCI) can be used to control ambulation within a
      virtual reality environment (VRE), suggesting that a BCI-controlled lower
      extremity prosthesis for ambulation may be feasible. However, the operability of
      our BCI has not yet been tested in a SCI population. METHODS: Five participants
      with paraplegia or tetraplegia due to SCI underwent a 10-min training session in
      which they alternated between kinesthetic motor imagery (KMI) of idling and
      walking while their electroencephalogram (EEG) were recorded. Participants then
      performed a goal-oriented online task, where they utilized KMI to control the
      linear ambulation of an avatar while making 10 sequential stops at designated
      points within the VRE. Multiple online trials were performed in a single day, and
      this procedure was repeated across 5 experimental days. RESULTS: Classification
      accuracy of idling and walking was estimated offline and ranged from 60.5% (p =
      0.0176) to 92.3% (p = 1.36*10-20) across participants and days. Offline analysis
      revealed that the activation of mid-frontal areas mostly in the MU and low beta
      bands was the most consistent feature for differentiating between idling and
      walking KMI. In the online task, participants achieved an average performance of
      7.4+/-2.3 successful stops in 273+/-51 sec. These performances were purposeful,
      i.e. significantly different from the random walk Monte Carlo simulations
      (p<0.01), and all but one participant achieved purposeful control within the
      first day of the experiments. Finally, all participants were able to maintain
      purposeful control throughout the study, and their online performances improved
      over time. CONCLUSIONS: The results of this study demonstrate that SCI
      participants can purposefully operate a self-paced BCI walking simulator to
      complete a goal-oriented ambulation task. The operation of the proposed BCI
      system requires short training, is intuitive, and robust against participant-to
      participant and day-to-day neurophysiological variations. These findings indicate
      that BCI-controlled lower extremity prostheses for gait rehabilitation or
      restoration after SCI may be feasible in the future.

PMID- 23866986
TI  - A novel function prediction approach using protein overlap networks.
AB  - BACKGROUND: Construction of a reliable network remains the bottleneck for network
      based protein function prediction. We built an artificial network model called
      protein overlap network (PON) for the entire genome of yeast, fly, worm, and
      human, respectively. Each node of the network represents a protein, and two
      proteins are connected if they share a domain according to InterPro database.
      RESULTS: The function of a protein can be predicted by counting the occurrence
      frequency of GO (gene ontology) terms associated with domains of direct
      neighbors. The average success rate and coverage were 34.3% and 43.9%,
      respectively, for the test genomes, and were increased to 37.9% and 51.3% when a
      composite PON of the four species was used for the prediction. As a comparison,
      the success rate was 7.0% in the random control procedure. We also made
      predictions with GO term annotations of the second layer nodes using the
      composite network and obtained an impressive success rate (>30%) and coverage
      (>30%), even for small genomes. Further improvement was achieved by statistical
      analysis of manually annotated GO terms for each neighboring protein.
      CONCLUSIONS: The PONs are composed of dense modules accompanied by a few long
      distance connections. Based on the PONs, we developed multiple approaches
      effective for protein function prediction.

PMID- 23866987
TI  - Non-fatal overdose among adult prisoners with a history of injecting drug use in
      two Australian states.
AB  - BACKGROUND: Recently released prisoners are at markedly increased risk of death
      and drug-related causes predominate. Non-fatal overdose (NFOD) is considerably
      more common than fatal overdose, but has received relatively little research
      attention and most studies of NFOD in this population have suffered from small
      samples of unknown representativeness. This study aimed to estimate the
      prevalence and correlates of lifetime NFOD among prisoners in NSW and Queensland.
      METHODS: Cross-sectional surveys of adult prisoners in two Australian states: New
      South Wales (n=972) and Queensland (n=1316). Use of similar measures and methods
      in the two states made direct comparison of findings possible. RESULTS: In both
      NSW and Queensland, 23% of participants reported a lifetime history of NFOD and
      prisoners with a history of injecting drug use were significantly more likely to
      report lifetime NFOD. The lifetime prevalence of NFOD among prisoners with a
      history of injecting drug use was significantly higher in NSW than in Queensland
      (44% vs. 35%; p<0.01). Independent correlates of lifetime NFOD were similar
      across the two states and included ever attempting suicide, ever injecting
      heroin, and ever injecting opioids. CONCLUSIONS: The risk of NFOD among prisoners
      with a history of injecting drug use is high. An understanding of the risk
      factors for NFOD in this population can inform targeted, evidence-based
      interventions to reduce this risk.

PMID- 23866988
TI  - Reinforcing integrated psychiatric service attendance in an opioid-agonist
      program: a randomized and controlled trial.
AB  - BACKGROUND: The benefits of integrating substance abuse and psychiatric care may
      be limited by poor service utilization. This randomized clinical trial evaluated
      the efficacy of using contingency management to improve utilization of
      psychiatric services co-located and integrated within a community-based methadone
      maintenance treatment program. METHODS: Opioid-dependent outpatients (n=125) with
      any current psychiatric disorder were randomly assigned to: (1) reinforced on
      site integrated care (ROIC), with vouchers (worth $25.00) contingent on full
      adherence to each week of scheduled psychiatric services; or (2) standard on-site
      integrated care (SOIC). All participants received access to the same schedule of
      psychiatrist and mental health counseling sessions for 12-weeks. RESULTS: ROIC
      participants attended more overall psychiatric sessions at month 1 (M=7.53 vs.
      3.97, p<.001), month 2 (M=6.31 vs. 2.81, p<.001), and month 3 (M=5.71 vs. 2.44,
      p<.001). Both conditions evidenced reductions in psychiatric distress (p<.001)
      and similar rates of drug-positive urine samples. No differences in study
      retention were observed. CONCLUSIONS: These findings suggest that contingency
      management can improve utilization of psychiatric services scheduled within an on
      site and integrated treatment model. Delivering evidenced-based mental health
      counseling, or modifying the contingency plan to include illicit drug use, may be
      required to facilitate greater changes in psychiatric and substance abuse
      outcomes.

PMID- 23866989
TI  - Inferential explanations in biology.
AB  - Among philosophers of science, there is now a widespread agreement that the DN
      model of explanation is poorly equipped to account for explanations in biology.
      Rather than identifying laws, so the consensus goes, researchers explain
      biological capacities by constructing a model of the underlying mechanism. We
      think that the dichotomy between DN explanations and mechanistic explanations is
      misleading. In this article, we argue that there are cases in which biological
      capacities are explained without constructing a model of the underlying
      mechanism. Although these explanations do not conform to Hempel's DN model (they
      do not deduce the explanandum from laws of nature), they do invoke more or less
      stable generalisations. Because they invoke generalisations and have the form of
      an argument, we call them inferential explanations. We support this claim by
      considering two examples of explanations of biological capacities: pigeon
      navigation and photoperiodism. Next, we will argue that these non-mechanistic
      explanations are crucial to biology in three ways: (i) sometimes, they are the
      only thing we have (there is no alternative available), (ii) they are
      heuristically useful, and (iii) they provide genuine understanding and so are
      interesting in their own right. In the last sections we discuss the relation
      between types of explanations and types of experiments and situate our views
      within some relevant debates on explanatory power and explanatory virtues.

PMID- 23866990
TI  - Descriptions and models: some responses to Abrams.

PMID- 23866991
TI  - Health communication meets artificial intelligence.

PMID- 23866992
TI  - Ascending curbs of progressively higher height increases forward trunk flexion
      along with upper extremity mechanical and muscular demands in manual wheelchair
      users with a spinal cord injury.
AB  - High upper extremity (U/E) demands are required when manual wheelchair users
      (MWUs) with spinal cord injury (SCI) ascend curbs; this may contribute to the
      risk of developing U/E musculoskeletal impairments. The aim of this study was to
      compare movement strategies (kinematics), mechanical loads (kinetics) and
      muscular demand (EMG) at the non-dominant U/E among 15 MWUs with SCI when
      ascending curbs of 4 cm (3 trials), 8 cm (3 trials) and 12 cm high (3 trials)
      from a starting line set 3 m before the curb. Biomechanical data was collected
      during three trials for each height. The curb ascent task was divided into three
      adjustment phases: caster pop, rear-wheel ascent and post-ascent. The greatest
      effort was generated by the shoulder flexors and internal rotators as well as the
      elbow flexors. A significant difference (p < 0.0167) between the curb heights was
      found for most outcome measures studied: movement excursion, net joint moments
      and muscular utilization ratio (MUR) of the main muscles increased with the
      higher curb heights, mainly around the shoulder joint. These results provide
      insight that aside from adhering to a highly structured training method for
      wheelchair curb ascent, rehabilitation professionals need to propose task
      specific strength training programs based on the demands documented in this study
      and continue to advocate for physically accessible environments.

PMID- 23866993
TI  - The association of smoking status with healthcare utilisation, productivity loss
      and resulting costs: results from the population-based KORA F4 study.
AB  - BACKGROUND: Smoking is seen as the most important single risk to health today,
      and is responsible for a high financial burden on healthcare systems and society.
      This population-based cross-sectional study compares healthcare utilisation,
      direct medical costs, and costs of productivity losses for different smoking
      groups: current smokers, former smokers, and never smokers. METHODS: Using a
      bottom-up approach, data were taken from the German KORA F4 study (2006/2008) on
      self-reported healthcare utilisation and work absence due to illness for 3,071
      adults aged 32-81 years. Unit costs from a societal perspective were applied to
      utilisation. Utilisation and resulting costs were compared across different
      smoking groups using generalised linear models to adjust for age, sex, education,
      alcohol consumption and physical activity. RESULTS: Average annual total costs
      per survey participant were estimated as ?3,844 [95% confidence interval: 3,447
      4,233], and differed considerably between smoking groups with never smokers
      showing ?3,237 [2,802-3,735] and former smokers causing ?4,398 [3,796-5,058].
      There was a positive effect of current and former smoking on the utilisation of
      healthcare services and on direct and indirect costs. Total annual costs were
      more than 20% higher (p<0.05) for current smokers and 35% higher (p<0.01) for
      former smokers compared with never smokers, which corresponds to annual excess
      costs of ?743 and ?1,108 per current and former smoker, respectively.
      CONCLUSIONS: Results indicate that excess costs for current and former smokers
      impose a large burden on society, and that previous top-down cost approaches
      produced lower estimates for the costs of care for smoking-related diseases.
      Efforts must be focused on prevention of smoking to achieve sustainable
      containment on behalf of the public interest.

PMID- 23866994
TI  - A clinical manifestation-based prediction of haemodynamic patterns of orthostatic
      intolerance in children: a multi-centre study.
AB  - OBJECTIVE: At present, the haemodynamic diagnosis of orthostatic intolerance is
      based mainly on the head-up tilt table test, which is sometimes risky for
      patients. Thus, it is important to find objective and safe methods to
      differentiate haemodynamic patterns of orthostatic intolerance cases. METHODS: In
      all, 629 children with orthostatic intolerance, either vasovagal syncope or
      postural orthostatic tachycardia syndrome, were included in the multi-centre
      clinical study. We analysed the association between the clinical manifestation
      and haemodynamic patterns of the patients. RESULTS: Syncope after motion with a
      prodrome of chest distress or palpitations and the concomitant symptom(s) after a
      syncopal attack, with debilitation, dizziness or headache, were the most
      important variables in predicting the diagnosis of vasovagal syncope. The overall
      diagnostic accuracy was 71.5%. CONCLUSION: Complaint of syncope after motion with
      prodromal chest distress or palpitation and the concomitant symptom after a
      syncopal attack, with subsequent debilitation, dizziness or headache, were the
      most important variables in the diagnosis of vasovagal syncope in children with
      orthostatic intolerance.

PMID- 23866995
TI  - Ellagic acid inhibits PDGF-BB-induced vascular smooth muscle cell proliferation
      and prevents atheroma formation in streptozotocin-induced diabetic rats.
AB  - Plant-derived polyphenolic compounds have beneficial health effects. In the
      present study, we determined the ability of ellagic acid (EA) to prevent platelet
      derived growth factor-BB (PDGF-BB)-induced proliferation of primary cultures of
      rat aortic smooth muscle cells (RASMCs). We also determined the ability of EA to
      prevent atherosclerosis in streptozotocin-induced diabetic rats. Proliferation of
      cells was measured via Alamar Blue assay and through propidium iodide-based cell
      cycle analysis in flow cytometer. Reactive oxygen species (ROS) were measured via
      2',7'-dichlorofluorescin diacetate and Amplex red methods. Expression of
      proliferation markers and activation of kinases were assessed by immunoblot
      analysis. Cotreatment of primary cultures of RASMCs with 25 MUmol/L of EA
      significantly reduced PDGF-BB (20 ng/ml)-induced proliferation by blocking S
      phase entry. EA effectively blocked PDGF receptor-beta (PDGFR-beta) tyrosine
      phosphorylation, generation of intracellular ROS and downstream activation of
      extracellular signal-regulated kinase 1/2. It also blocked PDGF-BB-induced
      expression of cyclin D1. Computational molecular docking of EA with the PDGFR
      beta-PDGF-BB complex revealed two putative inhibitor binding sites which showed
      similar binding energies with the known PDGFR-beta inhibitor AG1295. In diabetic
      rats, supplementation of diet with 2% EA significantly blocked diabetes-induced
      medial thickness, and lipid and collagen deposition in the arch of aorta. These
      were assessed through haematoxylin and eosin, Oil Red O and Masson's trichome
      staining, respectively. EA treatment also blocked cyclin D1 expression in medial
      smooth muscle cells in experimental animals. Thus, EA is effective in reducing
      atherosclerotic process by blocking proliferation of vascular smooth muscle
      cells.

PMID- 23866996
TI  - Comparative survey of entomophagy and entomotherapeutic practices in six tribes
      of eastern Arunachal Pradesh (India).
AB  - A consolidated list of edible insects used in the eastern part of Arunachal
      Pradesh (N.E. India) by Wangcho (Wancho) and Nocte tribes of the Tirap District
      and the Shingpo, Tangsa, Deori and Chakma of the Changlang District has been
      prepared. The list is based on thorough, semi-structured field-interviews with 20
      informants of each tribal group. At least 51 insect species, belonging to 9
      orders were considered edible. The largest number of the edible species belonged
      to the Coleoptera (14), followed by 10 each of the Orthoptera and Hymenoptera, 9
      of the Hemiptera, 3 Lepidoptera, 2 Isoptera and one each of Ephemeroptera,
      Odonata and Mantodea. As far as therapeutic uses of insects are concerned, 4
      species (Hemiptera) were mentioned by the Wangcho (Wancho). Food insects are
      chosen by members of the various tribes according to traditional beliefs, taste,
      regional and seasonal availability of the insects. Depending on the species, only
      certain, but sometimes all, developmental stages are consumed. Preparation of the
      food insects for consumption involves mainly roasting or boiling. With the
      degradation of natural resources, habitat loss, rapid population growth, and
      increasing 'westernization' , the traditional wisdom of North-East Indian tribals
      related to insect uses is at risk of being lost. 

PMID- 23866997
TI  - A note on relevance of diagnostic classification and rating scales used in
      psychiatry.
AB  - In the clinical practice of psychology and psychiatry, presence or absence of
      particular disorder or syndromes is based on the subjective interpretation of
      mental and behavioral descriptions offered by the patient. This is often done by
      questionnaires (also called instruments or scales) or by interviews. This
      subjectivity of the diagnostic decision-making process may limit the reliability
      of diagnosis. In the present study, a new method of scale relevance, based on
      double cluster analysis, is proposed as it is important to verify what we are
      trying to find with the proposed scale. If two data sets cluster differently, we
      must consider them as different. 

PMID- 23866998
TI  - A theoretical model of dentinogenesis: dentin and dentinal tubule formation.
AB  - INTRODUCTION: Dentinogenesis, odontoblast dentin formation, includes dentinal
      growth, mineralization and dentinal tubule formation. Odontoblasts synthesize
      collagen resulting in collagen apposition contributing to dentinogenesis.
      Furthermore, within the tubule, they express non-collagenous proteins, such as
      dentin phosphoprotein (DPP), associated with hydroxyapatite crystal formation and
      growth. The aim of this work was to determine patterns of growth and dentin
      formation and quantification of its mineralization. Findings from our work are
      relevant to endodontics for future regenerative treatment. METHODS: We formulated
      a 3D domain mathematical model, which recreates the events that lead to dentinal
      tubule mineralization. As reference we used collagen apposition and DPP activity.
      RESULTS: We obtained a model depicting predentin's mineralization distribution
      during dentin development. Furthermore, we verified different DPP diffusion
      coefficients to test the model's sensitivity. CONCLUSIONS: We present a model to
      shed light on the process of dentin and dentinal tubule formation, and its
      relation to diffusion and mineralization processes.

PMID- 23866999
TI  - Development of a new software for comprehensive management and traceability of
      hospital radiopharmacies.
AB  - A database software application for comprehensive management and traceability of
      hospital radiopharmacies has been developed and implemented. This software is a
      customizable shareware called Radiolab, which provides an immediate and complete
      traceability of all preparations, controls and radiopharmaceuticals, as well as a
      great help in the management of reports, orders, stock and radioactive waste.
      Available by now in five languages (English, Spanish, French, Portuguese and
      Italian) this software and its manual can be downloaded from the Internet at
      www.radiopharmacy.net. 

PMID- 23867000
TI  - Perceptions about the harm of secondhand smoke exposure among U.S. middle and
      high school students: findings from the 2012 National Youth Tobacco Survey.
AB  - BACKGROUND: Increased knowledge of the harmful effects of SHS is an evidence
      based key indicator for eliminating nonsmokers' exposure to SHS. This study
      assessed the prevalence and predictors of perceptions about the harm of
      secondhand smoke (SHS) exposure among U.S. middle and high school students.
      FINDINGS: Data were obtained from the 2012 National Youth Tobacco Survey, a
      nationally representative school-based survey of U.S. students in grades 6-12.
      Respondents who reported that they thought breathing smoke from other people's
      cigarettes or other tobacco products causes "some" or "a lot" of harm were
      considered to have the perception that SHS is harmful. Multivariate logistic
      regression was used to identify predictors of the perception that SHS is harmful.
      Predictors included sex, race/ethnicity, school grade level, current tobacco use,
      and whether the respondent currently lived with a tobacco user. Overall, 75.4% of
      students perceived SHS exposure as harmful. The adjusted odds of perceiving SHS
      exposure as harmful were higher among non-Hispanic Asians than among non-Hispanic
      whites, and among students in 10th-12th grades than among students in 8th grade.
      Adjusted odds were lower among boys than among girls, among non-Hispanic blacks
      than among non-Hispanic whites, among students living with a tobacco user than
      among those not, and among those who use combustible tobacco only or both
      combustible and non-combustible tobacco than among those who use no tobacco.
      CONCLUSIONS: Most middle and high school students perceive SHS exposure as
      harmful, but efforts are needed to increase the prevalence of this perception in
      certain subpopulations, particularly tobacco users.

PMID- 23867001
TI  - Bax Inhibitor-1-mediated Ca2+ leak is decreased by cytosolic acidosis.
AB  - Bax Inhibitor-1 (BI-1) is an evolutionarily conserved six-transmembrane domain
      endoplasmic reticulum (ER)-localized protein that protects against ER stress
      induced apoptotic cell death. This function is closely connected to its ability
      to lower steady-state ER Ca2+ levels. Recently, we elucidated BI-1's Ca(2+)
      channel pore in the C-terminal part of the protein and identified the critical
      amino acids of its pore. Based on these insights, a Ca(2+)-channel pore-dead
      mutant BI-1 (BI-1(D213R)) was developed. We determined whether BI-1 behaves as a
      bona fide H+/Ca2+ antiporter or as an ER Ca(2+)-leak channel by investigating the
      effect of pH on unidirectional Ca(2+)-efflux rates. At pH 6.8, wild-type BI-1
      expression in BI-1(-/-) cells increased the ER Ca(2+)-leak rate, correlating with
      its localization in the ER compartment. In contrast, BI-1(D231R) expression in BI
      1(-/-), despite its ER localization, did not increase the ER Ca(2+)-leak rate.
      However, at pH < 6.8, the BI-1-mediated ER Ca2+ leak was blocked. Finally, a
      peptide representing the Ca(2+)-channel pore of BI-1 promoting Ca2+ flux from the
      ER was used. Lowering the pH from 6.8 to 6.0 completely abolished the ability of
      the BI-1 peptide to mediate Ca2+ flux from the ER. We propose that this pH
      dependence is due to two aspartic acid residues critical for the function of the
      Ca(2+)-channel pore and located in the ER membrane-dipping domain, which
      facilitates the protonation of these residues.

PMID- 23867002
TI  - How calcium signals in myocytes and pericytes are integrated across in situ
      microvascular networks and control microvascular tone.
AB  - The microcirculation is the site of gas and nutrient exchange. Control of central
      or local signals acting on the myocytes, pericytes and endothelial cells within
      it, is essential for health. Due to technical problems of accessibility, the
      mechanisms controlling Ca2+ signalling and contractility of myocytes and
      pericytes in different sections of microvascular networks in situ have not been
      investigated. We aimed to investigate Ca2+ signalling and functional responses,
      in a microcirculatory network in situ. Using live confocal imaging of ureteric
      microvascular networks, we have studied the architecture, morphology, Ca2+
      signalling and contractility of myocytes and pericytes. Ca2+ signals vary between
      distributing arcade and downstream transverse and precapillary arterioles, are
      modified by agonists, with sympathetic agonists being ineffective beyond
      transverse arterioles. In myocytes and pericytes, Ca2+ signals arise from Ca2+
      release from the sarcoplasmic reticulum through inositol 1,4,5-trisphosphate
      induced Ca2+ release and not via ryanodine receptors or Ca2+ entry into the cell.
      The responses in pericytes are less oscillatory, slower and longer-lasting than
      those in myocytes. Myocytes and pericytes are electrically coupled, transmitting
      Ca2+ signals between arteriolar and venular networks dependent on gap junctions
      and Ca2+ entry via L-type Ca2+ channels. Endothelial Ca2+ signalling inhibits
      intracellular Ca2+ oscillations in myocytes and pericytes via L-arginine/nitric
      oxide pathway and intercellular propagating Ca2+ signals via EDHF. Increases of
      Ca2+ in pericytes and myocytes constrict all vessels except capillaries. These
      data reveal the structural and signalling specializations allowing blood flow to
      be regulated by myocytes and pericytes.

PMID- 23867003
TI  - Targeting 3-phosphoinositide-dependent protein kinase 1 by N-acetyl-cysteine
      through activation of peroxisome proliferators activated receptor alpha in human
      lung cancer cells, the role of p53 and p65.
AB  - BACKGROUND: N-Acetyl-Cysteine (NAC), a natural sulfur-containing amino acid
      derivative, and peroxisome proliferators activated receptor alpha (PPARalpha)
      ligand have been shown to have anticancer properties. However, the mechanisms by
      which these agents inhibit human non-small cell lung carcinoma (NSCLC) cell
      growth have not been well elucidated. METHODS: Small interfering RNAs (siRNAs)
      were used to knockdown 3-phosphoinositide-dependent protein kinase 1 (PDK1),
      PPARalpha, p65 and p53 genes; Western Blot was performed to detect the protein
      expression of PDK1, PPARalpha, p65 and p53; Cell viability and MTT assays were
      carried out to determine the cell proliferation; Transient transfection and Dual
      Luciferase Reporter assays were used to transfect siRNAs or exogenous expression
      vectors, and to measure the gene promoter activity. RESULTS: We showed that NAC
      inhibited NSCLC cell proliferation through reduction of PDK1 expression. NAC also
      induced the protein expression of PPARalpha. While PPARalpha ligand enhanced,
      PPARalpha antagonist and siRNA abrogated the effect of NAC on PDK1 promoter
      activity, protein expression and cell growth. Overexpression of PDK1 diminished
      the inhibitory effect of NAC on cell proliferation. NAC induced p53 and reduced
      p65 protein expression through activation of PPARalpha. Silencing of p53 and
      overexpression of p65 blocked the effect of NAC on PDK1 promoter activity and
      protein expression. CONCLUSION: Our results show that NAC inhibits PDK1
      expression through PPARalpha-mediated induction of p53 and inhibition of p65
      protein expression. PPARalpha ligand enhances the effect of NAC. This ultimately
      inhibits NSCLC cell growth. This study unveils a novel mechanism by which NAC in
      combination with PPARalpha ligand inhibits growth of human lung carcinoma cells.

PMID- 23867004
TI  - Farm and management characteristics associated with boar taint.
AB  - Pig farms in the Netherlands producing boars have different levels of boar taint
      prevalence, as assessed by sensory evaluation with the human nose at the
      slaughter line. With a questionnaire to 152 Dutch pig producers (response rate
      59%), farm and management characteristics were identified that are potentially
      associated with farm-level boar taint prevalence. Lower farm-level boar taint
      prevalence was associated with a smaller group size, a smaller pen surface per
      boar, newer housing equipment, not practicing restricted feeding in the last
      period before delivery, a longer fasting period before slaughter, a higher
      stocking weight and a lower fraction of boars from purebred dam line sows or from
      Pietrain terminal boars. These characteristics can be used to develop farm-level
      intervention strategies to control boar taint. More research effort is needed to
      establish causal relationships. 

PMID- 23867005
TI  - Leg surface electromyography patterns in children with neuro-orthopedic disorders
      walking on a treadmill unassisted and assisted by a robot with and without
      encouragement.
AB  - BACKGROUND: Robot-assisted gait training and treadmill training can complement
      conventional physical therapy in children with neuro-orthopedic movement
      disorders. The aim of this study was to investigate surface electromyography
      (sEMG) activity patterns during robot-assisted gait training (with and without
      motivating instructions from a therapist) and unassisted treadmill walking and to
      compare these with physiological sEMG patterns. METHODS: Nine children with motor
      impairments and eight healthy children walked in various conditions: (a) on a
      treadmill in the driven gait orthosis Lokomat(r), (b) same condition, with
      additional motivational instructions from a therapist, and (c) on the treadmill
      without assistance. sEMG recordings were made of the tibialis anterior,
      gastrocnemius lateralis, vastus medialis, and biceps femoris muscles. Differences
      in sEMG amplitudes between the three conditions were analyzed for the duration of
      stance and swing phase (for each group and muscle separately) using non
      parametric tests. Spearman's correlation coefficients illustrated similarity of
      muscle activation patterns between conditions, between groups, and with published
      reference trajectories. RESULTS: The relative duration of stance and swing phase
      differed between patients and controls, and between driven gait orthosis
      conditions and treadmill walking. While sEMG amplitudes were higher when being
      encouraged by a therapist compared to robot-assisted gait training without
      instructions (0.008 <= p-value <= 0.015), muscle activation patterns were highly
      comparable (0.648 <= Spearman correlation coefficients <= 0.969). In general,
      comparisons of the sEMG patterns with published reference data of over-ground
      walking revealed that walking in the driven gait orthosis could induce more
      physiological muscle activation patterns compared to unsupported treadmill
      walking. CONCLUSIONS: Our results suggest that robotic-assisted gait training
      with therapeutic encouragement could appropriately increase muscle activity.
      Robotic-assisted gait training in general could induce physiological muscle
      activation patterns, which might indicate that this training exploits restorative
      rather than compensatory mechanisms.

PMID- 23867006
TI  - Reaction of 2,6-dichloroquinone-4-chloroimide (Gibbs reagent) with permethrin -
      an optical sensor for rapid detection of permethrin in treated wood.
AB  - BACKGROUND: A novel optical sensor for the rapid and direct determination of
      permethrin preservatives in treated wood was designed. The optical sensor was
      fabricated from the immobilisation of 2,6-dichloro-p-benzoquinone-4-chloroimide
      (Gibbs reagent) in nafion/sol-gel hybrid film and the mode of detection was based
      on absorption spectrophotometry. Physical entrapment was employed as a method of
      immobilisation. RESULTS: The sensor gave a linear response range of permethrin
      between 2.56-383.00 MUM with detection limit of 2.5 MUM and demonstrated good
      repeatability with relative standard deviation (RSD) for 10 MUM at 5.3%, 100 MUM
      at 2.7%, and 200 MUM at 1.8%. The response time of the sensor was 40 s with an
      optimum response at pH 11. CONCLUSIONS: The sensor was useful for rapid screening
      of wood or treated wood products before detailed analysis using tedious procedure
      is performed. The validation study of the optical sensor against standard method
      HPLC successfully showed that the permethrin sensor tended to overestimate the
      permethrin concentration determined.

PMID- 23867007
TI  - First two cases of neonatal human parechovirus 4 infection with manifestation of
      suspected sepsis, Finland.
AB  - Human parechoviruses are a family of viruses closely related to enteroviruses,
      and associated with neonatal sepsis-like syndrome, respiratory symptoms and
      gastrointestinal infection. Here we present clinical details of two neonatal
      sepsis cases suspected to be caused by HPeV4 infection. The patients were
      hospitalized in October, 2012. No other causative agents were detected. 

PMID- 23867008
TI  - Comparison of use of vaginal HPV self-sampling and offering flexible appointments
      as strategies to reach long-term non-attending women in organized cervical
      screening.
AB  - BACKGROUND: Many cervical cancers occur among women who have not attended
      cervical screening. Strategies to reach non-attending women may improve the
      effectiveness of cervical screening programmes. OBJECTIVE: To compare the
      responses among long-term non-attending women to either (i) HPV-testing of a self
      collected vaginal sample, or (ii) cytological screening with a flexible no-fee
      appointment for sampling at an outpatient clinic. STUDY DESIGN: Among the 242,000
      women aged 32-65 years in Southern Sweden, we identified 28,635 women who had not
      had any cervical smears taken for >9 years. We randomized 1000 women to
      invitation to HPV self-sampling, and 500 women to flexible outpatient clinic
      appointments. Responding women received a questionnaire about their reasons for
      previous non-attendance. RESULTS: The response rate to HPV self-sampling was
      three times higher than the flexible outpatient clinic invitations (147/1000
      women (14.7%) compared to 21/500 (4.2%) p<0.0001). High-risk (hr)-HPV was found
      in 10/147 self-sampled women (6.9%). 7/10 hr-HPV-positive women attended
      colposcopy, but no HSIL was found. Among the clinic-sampled women, 2/21 had hr
      HPV and 1/21 had HSIL. Reasons for not attending were "uncomfortable with vaginal
      examination", "feel healthy", "lack of time" and "experience of unfriendly health
      workers". CONCLUSIONS: Although the response rate was low for both interventions,
      the invitation to vaginal HPV self-sampling was more effective for increasing the
      coverage of the screening programme. The fact that "uncomfortable with vaginal
      examination" was the most common reason for non-attending suggests that self
      sampling could be further explored as a strategy to increase the coverage of
      cervical screening programmes.

PMID- 23867009
TI  - The influence of cerebrospinal fluid on epidermal neural crest stem cells may
      pave the path for cell-based therapy.
AB  - INTRODUCTION: Epidermal neural crest stem cells (EPI-NCSCs) in the bulge of hair
      follicles are a promising source for cell-replacement therapies in
      neurodegenerative diseases. A prominent factor in cell-based therapy is the
      practicalities of different routes of administration. Cerebrospinal fluid (CSF),
      owing to its adaptive library of secreted growth factors, can provide a trophic
      environment for transplanted cells. Thus, the effect of CSF on the behavior of
      EPI-NCSC was studied here. METHODS: In this study, the highly pure population of
      EPI-NCSCs was obtained from the bulge of mouse hair follicle. Migrated cells were
      characterized with real-time polymerase chain reaction (RT-PCR) and
      immunocytochemistry. Subsequently isolated stem cells were cultured in CSF, which
      was collected from the cisterna magna of the adult rat. The expression of
      pertinent markers was assessed at the gene and protein levels with RT-PCR and
      immunocytochemistry, respectively. Colorimetric immunoassay was used to quantify
      the rate of proliferation of EPI-NCSCs after cultivation in CSF. RESULTS:
      Isolated EPI-NCSCs could survive in the CSF, and they maintained the expression
      of nestin, beta-tubulin III (early neuronal marker), and glial fibrillary acidic
      protein (GFAP, glia marker) in this environment. In addition, CSF decreased the
      proliferation rate of EPI-NCSCs significantly in comparison to primary and
      expansion culture medium. CONCLUSIONS: Our findings demonstrate that CSF as a
      cocktail of growth factors helps EPI-NCSCs to acquire some desirable traits, and
      because of its circulatory system that is in close contact with different parts
      of the central nervous system (CNS), can be a practical route of administration
      for delivery of injected stem cells.

PMID- 23867010
TI  - The use of a central beam stop for contrast enhancement in TEM imaging.
AB  - Dark field TEM imaging using a stop of the central beam (DF-000) is reported. It
      is shown that a strong enhancement in the contrast can be obtained for graphene
      as example of weak phase object and endocytic multivescilar body as example of an
      unstained biological sample. No charging or significant contamination of the
      central beam stop is observed. For graphene, a resolution beyond 1A(-1) was
      easily obtained. DF-000 imaging can be considered as a good and easy to use
      alternative of a phase plate. 

PMID- 23867011
TI  - Letter to the Editor Multifaceted impairments of impulsivity in cannabis users? -
      a reply.

PMID- 23867012
TI  - Glycoprotein B (gB) vaccines adjuvanted with AS01 or AS02 protect female guinea
      pigs against cytomegalovirus (CMV) viremia and offspring mortality in a CMV
      challenge model.
AB  - The transmission of cytomegalovirus (CMV) from mother to fetus can give rise to
      severe neurodevelopment defects in newborns. One strategy to prevent these
      congenital defects is prophylactic vaccination in young women. A candidate
      vaccine antigen is glycoprotein B (gB). This antigen is abundant on the virion
      surface and is a major target of neutralization responses in human infections.
      Here, we have evaluated in a challenge model of congenital guinea pig CMV (GPCMV)
      infection, GPCMV-gB vaccines formulated with the clinically relevant Adjuvant
      Systems AS01B and AS02V, or with Freund's adjuvant (FA). Fifty-two GPCMV
      seronegative female guinea pigs were administered three vaccine doses before
      being mated. GPCMV-challenge was performed at Day 45 of pregnancy (of an
      estimated 65 day gestation). Pup mortality rates in the gB/AS01B, gB/AS02V, and
      gB/FA groups were 24% (8/34), 10% (4/39) and 36% (12/33), respectively, and in
      the unvaccinated control group was 65% (37/57). Hence, efficacies against pup
      mortality were estimated at 64%, 84% and 44% for gB/AS01B (p<0.001), gB/AS02V
      (p<0.001) and gB/FA (p=0.014), respectively. Efficacies against GPCMV viremia
      (i.e. DNAemia, detected by PCR) were estimated at 88%, 68% and 25% for the same
      vaccines, respectively, but were only significant for gB/AS01B (p<0.001), and
      gB/AS02V (p=0.002). In dams with viremia, viral load was approximately 6-fold
      lower with vaccination than without. All vaccines were highly immunogenic after
      two and three doses. In light of these results and of other results of AS01
      adjuvanted vaccines in clinical development, vaccine immunogenicity was further
      explored using human CMV-derived gB antigen adjuvanted with either AS01B or the
      related formulation AS01E. Both adjuvanted vaccines were highly immunogenic after
      two doses, in contrast to the lower immunogenicity of the unadjuvanted vaccine.
      In conclusion, the protective efficacy and immunogenicity of adjuvanted vaccines
      in this guinea pig model are supportive of investigating gB/AS01 and gB/AS02 in
      the clinic. 

PMID- 23867013
TI  - High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic
      dog populations in South Africa precludes the use of CAV-based recombinant rabies
      vaccines.
AB  - Rabies in dogs can be controlled through mass vaccination. Oral vaccination of
      domestic dogs would be useful in the developing world, where greater vaccination
      coverage is needed especially in inaccessible areas or places with large numbers
      of free-roaming dogs. From this perspective, recent research has focused on
      development of new recombinant vaccines that can be administered orally in a bait
      to be used as adjunct for parenteral vaccination. One such candidate, a
      recombinant canine adenovirus type 2 vaccine expressing the rabies virus
      glycoprotein (CAV2-RG), is considered a promising option for dogs, given host
      specificity and safety. To assess the potential use of this vaccine in domestic
      dog populations, we investigated the prevalence of antibodies against canine
      adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from
      the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been
      vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2
      (CAV2). Animals from both provinces had a high percentage of seropositivity (45%
      and 62%), suggesting that CAV2 circulates extensively among domestic dog
      populations in South Africa. Given this finding, we evaluated the effect of pre
      existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered
      via the oral route in dogs. Purpose-bred Beagle dogs, which received prior
      vaccination against canine parvovirus, canine distemper virus and CAV, were
      immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection
      all animals, except one vaccinated dog, developed rabies. This study demonstrated
      that pre-existing antibodies against CAV, such as naturally occurs in South
      African dogs, inhibits the development of neutralizing antibodies against RABV
      when immunized with a CAV-based rabies recombinant vaccine.

PMID- 23867014
TI  - Assessment of viral replication in eggs and HA protein yield of pre-pandemic H5N1
      candidate vaccine viruses.
AB  - H5N1 infection and the potential for spread from human to human continue to pose
      a severe public health concern. Since vaccination remains the most effective way
      to prevent a potential H5N1 pandemic, the World Health Organization (WHO)
      Collaborating Centers (CCs) and Essential Regulatory Laboratories (ERLs)
      engineered and developed a panel of H5N1 pre-pandemic vaccine viruses for
      pandemic vaccine preparedness as well as production of antigen potency testing
      reagents (reference antigen and reference anti-serum) for vaccine
      standardization. To develop a strategy utilizing a number of biochemical methods
      for the characterization of the viral growth properties and protein yield in
      eggs, we have selected eight H5N1 pre-pandemic viruses and determined the viral
      Egg Infectious Dose 50 (EID50), total protein yield, hemagglutinin (HA) to
      nucleoprotein (NP) ratios (HA:NP), and HA1 content of each virus. Our results
      showed that all the tested H5N1 vaccine viruses grew to high titers in eggs. The
      total viral protein yield varies within a narrow range, whereas there were
      greater differences in the HA:NP protein ratios among the eight viruses. The RP
      HPLC based HA1 content analysis demonstrated that the viruses A/Anhui/1/2010,
      A/Hubei/1/2005, and A/goose/Guiyang/337/2006 contained higher HA contents than
      other five viruses including A/Vietnam/1203/2003. Our approach for analyzing
      virus growth and protein yield will allow us identify optimal vaccine virus in a
      timely manner. In addition, we successfully purified the HA proteins of H5N1
      vaccine viruses by optimizing bromelain cleavage conditions. Our studies on the
      HA protein purification may improve the quality control of the production of
      influenza vaccine test reagent.

PMID- 23867015
TI  - How do anticipated worry and regret predict seasonal influenza vaccination uptake
      among Chinese adults?
AB  - OBJECTIVES: To test two hypothesized models of how anticipated affect, cognitive
      risk estimate and vaccination intention might influence vaccination uptake
      against seasonal influenza. METHODS: The study collected baseline and follow-up
      data during the main influenza seasons (January-March) of 2009 and 2010,
      respectively, among 507 university students and staff of a university in Hong
      Kong. Following logistic regression to determine eligible variables, two
      mediation models of cognitive risk estimate, anticipated affect, vaccination
      intention and vaccination uptake against seasonal influenza were tested using
      structural equation modeling. RESULTS: Mediation analyses found that anticipated
      worry if not vaccinated influenced seasonal influenza vaccination uptake through
      its effects on either perceived probability of influenza infection (beta=0.45) or
      intention (beta=0.45) while anticipated regret if not vaccinated influenced
      vaccination uptake through its effect on intention (beta=0.45) only; anticipated
      regret if vaccinated impeded vaccination uptake indirectly through its effect on
      vaccination intention (beta=-0.26) or directly (beta=-0.20); perceived
      probability of influenza infection influenced vaccination uptake through its
      effect on intention (beta=0.20) or directly (beta=0.22); and finally, intention
      influenced vaccination uptake directly (beta=0.58). CONCLUSION: The results
      suggest that anticipated affect seems to drive risk estimates related to seasonal
      influenza vaccination rather than vice versa and intention remains an important
      mediator of the associations of anticipated affect and cognitive risk estimate
      with vaccination uptake against seasonal influenza.

PMID- 23867016
TI  - A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific
      expression and guides synthetic regulatory element design.
AB  - BACKGROUND: Large-scale annotation efforts have improved our ability to coarsely
      predict regulatory elements throughout vertebrate genomes. However, it is unclear
      how complex spatiotemporal patterns of gene expression driven by these elements
      emerge from the activity of short, transcription factor binding sequences.
      RESULTS: We describe a comprehensive promoter extension assay in which the
      regulatory potential of all 6 base-pair (bp) sequences was tested in the context
      of a minimal promoter. To enable this large-scale screen, we developed algorithms
      that use a reverse-complement aware decomposition of the de Bruijn graph to
      design a library of DNA oligomers incorporating every 6-bp sequence exactly once.
      Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp
      oligomers, which is sufficiently compact for in vivo testing. We injected each
      multiplexed construct into zebrafish embryos and scored GFP expression in 15
      tissues at two developmental time points. Twenty-seven constructs produced
      consistent expression patterns, with the majority doing so in only one tissue.
      Functional sequences are enriched near biologically relevant genes, match motifs
      for developmental transcription factors, and are required for enhancer activity.
      By concatenating tissue-specific functional sequences, we generated completely
      synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic
      lateral line, and show that short regulatory sequences do not always function
      modularly. CONCLUSIONS: This work introduces a unique in vivo catalog of short,
      functional regulatory sequences and demonstrates several important principles of
      regulatory element organization. Furthermore, we provide resources for designing
      compact, reverse-complement aware k-mer libraries.

PMID- 23867017
TI  - The ER luminal binding protein (BiP) alleviates Cd(2+)-induced programmed cell
      death through endoplasmic reticulum stress-cell death signaling pathway in
      tobacco cells.
AB  - Cadmium (Cd) is very toxic to plant cells and Cd(2+) stress induces programmed
      cell death (PCD) in Nicotiana tabacum L. cv. bright yellow-2 (BY-2) cells. In
      plants, PCD can be regulated through the endoplasmic reticulum (ER) stress-cell
      death signaling pathway. However, the mechanism of Cd(2+)-induced PCD remains
      unclear. In this study, we found that Cd(2+) treatment induced ER stress in
      tobacco BY-2 cells. The expression of two ER stress markers NtBLP4 and NtPDI and
      an unfolded protein response related transcription factor NtbZIP60 were
      upregulated with Cd(2+) stress. Meanwhile, the PCD triggered by prolonged Cd(2+)
      stress could be relieved by two ER chemical chaperones, 4-phenylbutyric acid and
      tauroursodeoxycholic acid. These results demonstrate that the ER stress-cell
      death signaling pathway participates in the mediation of Cd(2+)-induced PCD.
      Furthermore, the ER chaperone AtBiP2 protein alleviated Cd(2+)-induced ER stress
      and PCD in BY-2 cells based on the fact that heterologous expression of AtBiP2 in
      tobacco BY-2 cells reduced the expression of NtBLP4 and a PCD-related gene
      NtHsr203J under Cd(2+) stress conditions. In summary, these results suggest that
      the ER stress-cell death signaling pathway regulates Cd(2+)-induced PCD in
      tobacco BY-2 cells, and that the AtBiP2 protein act as a negative regulator in
      this process. 

PMID- 23867018
TI  - The effect of premedication with ketamine, alone or with diazepam, on anaesthesia
      with sevoflurane in parrots (Amazona aestiva).
AB  - BACKGROUND: Premedication is rarely used in avian species. The aim of this study
      was to evaluate the effect of premedication on the quality of sevoflurane
      induction and anaesthesia in parrots. We hypothesised that premedication would
      facilitate handling and decrease the minimum anaesthetic dose (MAD). Thirty-six
      adult parrots were randomly distributed in three groups: group S (n = 12) was
      premedicated with NaCl 0.9%; group KS (n = 12) was premedicated with 10 mg.kg-1
      ketamine; and group KDS (n = 12) was premedicated with 10 mg.kg-1 ketamine and
      0.5 mg.kg-1 diazepam, delivered intramuscularly. After induction using 4.5%
      sevoflurane introduced through a facemask, the MAD was determined for each
      animal. The heart rate (HR), respiratory rate (RR), systolic arterial blood
      pressure (SAP), and cloacal temperature (CT) were recorded before premedication
      (T0), 15 minutes after premedication (T1), and after MAD determination (T2).
      Arterial blood gas analyses were performed at T0 and T2. The quality of
      anaesthesia was evaluated using subjective scales based on animal behaviour and
      handling during induction, maintenance, and recovery. Statistical analyses were
      performed using analysis of variance or Kruskal-Wallis tests followed by Tukey's
      or Dunn's tests. RESULTS: The minimal anaesthetic doses obtained were 2.4 +/-
      0.37%, 1.7 +/- 0.39%, and 1.3 +/- 0.32% for groups S, KS, and KDS, respectively.
      There were no differences in HR, RR, or CT among groups, but SAP was
      significantly lower in group S. Sedation was observed in both the premedicated S
      KS and S-KDS groups. There were no differences in the quality of intubation and
      recovery from anaesthesia among the three groups, although the induction time was
      significantly shorter in the pre-medicated groups, and the KS group showed less
      muscle relaxation. CONCLUSIONS: Ketamine alone or the ketamine/diazepam
      combination decreased the MAD of sevoflurane in parrots (Amazona aestiva).
      Ketamine alone or in combination with diazepam promoted a good quality of
      sedation, which improved handling and reduced the stress of the birds. All
      protocols provided safe anaesthesia in this avian species.

PMID- 23867019
TI  - Geospatial analysis for targeting out-of-hospital cardiac arrest intervention.
AB  - BACKGROUND: Bystander cardiopulmonary resuscitation (BCPR) provides an
      opportunity for decreasing cardiac mortality. Rates of out-of-hospital cardiac
      arrest (OHCA) in which resuscitation was performed vary within cities and across
      demographics. PURPOSE: To identify contiguous geographic census tracts with high
      OHCA, low BCPR rates and high-risk demographics to effectively target culturally
      appropriate community-based intervention planning. METHODS: In 2012, a cohort of
      11,389 emergency medical services (EMS) OHCA cases from Houston TX (2004-2011)
      was linked to census tracts. Multivariable logistic regression analyses were used
      to identify demographics of contiguous geographic census tracts with the highest
      OHCA rates. Within these tracts, BCPR rates were evaluated. The combination of
      information was used to develop a plan to better target interventions. RESULTS:
      Contiguous census tracts of high OHCA rates were identified; the average rate per
      100,000 within versus outside the identified tracts is 106.0 (SD 23.7) to 55.8
      (SD 19.7). Tracts with a low BCPR rate (37.7%) relative to a high OHCA rate were
      identified. In a separate analysis, individuals at highest relative risk of OHCA
      were found to be African Americans, to have low income or education levels, and
      to be older individuals. For every 1% increase in African Americans in a census
      tract, there is an increase of 2.7% in the relative risk of the census tract
      belonging to a high-OHCA-rate region (95% CI=2.0%, 3.5%). CONCLUSIONS: Geospatial
      analysis can provide important information on the contiguous areas of high OHCA
      rates and low BCPR rates with the aim of more effectively targeting interventions
      and ultimately decreasing cardiac deaths.

PMID- 23867020
TI  - School wellness policies and foods and beverages available in schools.
AB  - BACKGROUND: Since 2006-2007, education agencies (e.g., school districts)
      participating in U.S. federal meal programs are required to have wellness
      policies. To date, this is the only federal policy that addresses foods and
      beverages sold outside of school meals (in competitive venues). PURPOSE: To
      examine the extent to which federally required components of school wellness
      policies are associated with availability of foods and beverages in competitive
      venues. METHODS: Questionnaire data were collected in 2007-2008 through 2010-2011
      school years from 892 middle and 1019 high schools in nationally representative
      samples. School administrators reported the extent to which schools had required
      wellness policy components (goals, nutrition guidelines, implementation
      plan/person responsible, stakeholder involvement) and healthier and less-healthy
      foods and beverages available in competitive venues. Analyses were conducted in
      2012. RESULTS: About one third of students (31.8%) were in schools with all four
      wellness policy components. Predominantly white schools had higher wellness
      policy scores than other schools. After controlling for school characteristics,
      higher wellness policy scores were associated with higher availability of low-fat
      and whole-grain foods and lower availability of regular-fat/sugared foods in
      middle and high schools. In middle schools, higher scores also were associated
      with lower availability of 2%/whole milk. High schools with higher scores also
      had lower sugar-sweetened beverage availability and higher availability of
      1%/nonfat milk, fruits/vegetables, and salad bars. CONCLUSIONS: Because they are
      associated with lower availability of less-healthy and higher availability of
      healthier foods and beverages in competitive venues, federally required
      components of school wellness policies should be encouraged in all schools.

PMID- 23867021
TI  - School-day and overall physical activity among youth.
AB  - BACKGROUND: Increasing school-day physical activity through policy and programs
      is commonly suggested to prevent obesity and improve overall child health.
      However, strategies that focus on school-day physical activity may not increase
      total physical activity if youth compensate by reducing physical activity outside
      of school. PURPOSE: Objectively measured, nationally representative physical
      activity data were used to test the hypothesis that higher school-day physical
      activity is associated with higher overall daily physical activity in youth.
      METHODS: Accelerometer data from 2003-2004/2005-2006 National Health and
      Nutrition Examination Surveys were analyzed in 2012 to estimate physical activity
      levels during the school day (8AM-3PM) among youth aged 6-19 years (n=2548).
      Fixed-effects regressions were used to estimate the impact of changes in school
      day minutes of moderate-to-vigorous physical activity (MVPA) on changes in total
      daily MVPA. RESULTS: Each additional minute of school-day MVPA was associated
      with an additional 1.14 minutes (95% CI=1.04, 1.24; p<0.001) of total daily MVPA,
      or 0.14 additional minutes (95% CI=0.04, 0.24; p=0.008) outside the school day,
      controlling for total daily accelerometer wear time and age, gender,
      race/ethnicity, and other non-time varying covariates. There were no differences
      in the effect of school-day MVPA on total MVPA by age group, gender,
      race/ethnicity, poverty status, or degree of change in MVPA. CONCLUSIONS: Higher
      school-day MVPA was associated with higher daily MVPA among U.S. youth with no
      evidence for same-day "compensation." Increasing school-based physical activity
      is a promising approach that can improve total daily physical activity levels of
      youth.

PMID- 23867022
TI  - Walk Score(r) and Transit Score(r) and walking in the multi-ethnic study of
      atherosclerosis.
AB  - BACKGROUND: Walk Score(r) and Transit Score(r) are open-source measures of the
      neighborhood built environment to support walking ("walkability") and access to
      transportation. PURPOSE: To investigate associations of Street Smart Walk Score
      and Transit Score with self-reported transport and leisure walking using data
      from a large multicity and diverse population-based sample of adults. METHODS:
      Data from a sample of 4552 residents of Baltimore MD, Chicago IL, Forsyth County
      NC, Los Angeles CA, New York NY, and St. Paul MN from the Multi-Ethnic Study of
      Atherosclerosis (2010-2012) were linked to Walk Score and Transit Score
      (collected in 2012). Logistic and linear regression models estimated ORs of not
      walking and mean differences in minutes walked, respectively, associated with
      continuous and categoric Walk Score and Transit Score. All analyses were
      conducted in 2012. RESULTS: After adjustment for site, key sociodemographic, and
      health variables, a higher Walk Score was associated with lower odds of not
      walking for transport and more minutes/week of transport walking. Compared to
      those in a "walker's paradise," lower categories of Walk Score were associated
      with a linear increase in odds of not transport walking and a decline in minutes
      of leisure walking. An increase in Transit Score was associated with lower odds
      of not transport walking or leisure walking, and additional minutes/week of
      leisure walking. CONCLUSIONS: Walk Score and Transit Score appear to be useful as
      measures of walkability in analyses of neighborhood effects.

PMID- 23867023
TI  - Utility of the U.S. Preventive Services Task Force criteria for diabetes
      screening.
AB  - BACKGROUND: Federal law requires certain private insurers to cover and waive
      patient cost sharing for preventive medical services that receive a grade of B or
      better from the U.S. Preventive Services Task Force (USPSTF). The USPSTF
      recommends that asymptomatic adults who have a blood pressure (BP) higher than
      135/80 mmHg be screened for type 2 diabetes. PURPOSE: The goals of this study
      were to determine the sensitivity and specificity of the USPSTF screening
      criteria and to determine the prevalence of cardiovascular risk factors and
      comorbidity among undiagnosed individuals by USPSTF criteria. METHODS: Data come
      from 7189 adults who participated in the 2003-2010 National Health and Nutrition
      Examination Survey; statistical analysis was conducted in 2011-2012. Participants
      with fasting plasma glucose >=126 mg/dL or hemoglobin A1c (HbA1c) >=6.5% who did
      not self-report a diagnosis of diabetes were categorized as having undiagnosed
      diabetes. RESULTS: Among people without diagnosed diabetes, 4.0% had undiagnosed
      diabetes. The proportion of adults with undiagnosed diabetes who were identified
      (sensitivity) using BP >135/80 mmHg as the screening standard was 44.4%; among
      individuals without undiagnosed diabetes, 74.8% had BP <=135/80 mmHg
      (specificity). For those with undiagnosed diabetes, the prevalence of HbA1c 7.0%
      <8.0% was 10.6% for those with BP <=135/80 mmHg and 14.3% for those with BP
      >135/80 mmHg; and 12.8% and 9.4% for HbA1c >=8.0%, respectively. Elevated low
      density lipoprotein (100-160 mg/dL) was similar by BP cut-point (52%-53%). For
      those with BP <=135/80 mmHg, 16.7% had a history of cardiovascular disease and
      22.9% had chronic kidney disease. CONCLUSIONS: The USPSTF screening
      recommendations result in missing more than half of those who have undiagnosed
      diabetes, and a substantial proportion of these people have increased low-density
      lipoprotein and other cardiovascular risk factors.

PMID- 23867024
TI  - Challenges in cervical cancer prevention: a survey of U.S. obstetrician
      gynecologists.
AB  - BACKGROUND: Current cervical cancer prevention recommendations include human
      papillomavirus (HPV) vaccination, Pap and HPV co-testing, and Pap testing at 3-
      to 5-year intervals. PURPOSE: To examine attitudes, practice patterns, and
      barriers related to HPV vaccination and cervical cancer screening guidelines
      among U.S. obstetrician-gynecologists. METHODS: In 2011-2012, a national sample
      of members of the American Congress of Obstetricians and Gynecologists responded
      to a 15-item (some with multiple parts) questionnaire assessing sociodemographic
      characteristics, clinical practices, and perceived barriers to HPV vaccination
      and cervical cancer screening. Multivariate logistic regression was used to
      identify factors associated with guideline adherence. Analyses were conducted in
      2012. RESULTS: A total of 366 obstetrician-gynecologists participated. Ninety-two
      percent of respondents offered HPV vaccination to patients, but only 27%
      estimated that most eligible patients received vaccination. Parent and patient
      refusals were commonly cited barriers to HPV vaccination. Approximately half of
      respondents followed guidelines to begin cervical cancer screening at age 21
      years, discontinue screening at age 70 years or after hysterectomy, and
      appropriately utilize Pap and HPV co-testing. Most physicians continued to
      recommend annual Paps (74% aged 21-29 years, 53% aged >=30 years). Physicians
      felt that patients were uncomfortable with extended screening intervals and were
      concerned that patients would not come for annual exams without concurrent Paps.
      Solo practitioners were less likely to follow both vaccination and screening
      guidelines than those in group practices. CONCLUSIONS: This survey of
      obstetrician-gynecologists indicates persistent barriers to the adoption of HPV
      vaccination and cervical cancer screening guidelines. Interventions to promote
      guideline adherence may help improve the quality of cervical cancer prevention.

PMID- 23867025
TI  - Prostate-specific antigen testing: men's responses to 2012 recommendation against
      screening.
AB  - BACKGROUND: The U.S. Preventive Services Task Force (USPSTF) released a draft
      recommendation advising against prostate-specific antigen (PSA) testing in
      October 2011, a major shift from previous years of recommending neither for or
      against PSA testing due to insufficient evidence. PURPOSE: The purpose of this
      study was to assess men's awareness of the new recommendation, and their
      responses to it. METHODS: This study comprised a web survey of men aged 40-74
      years that was conducted through GfK Custom Research, LLC's Knowledge Panel(r)
      from November 22 to December 2, 2011. Chi-square tests and logistic regression
      analyses were conducted to identify factors associated with disagreement with and
      intention to follow the recommendation. Data were analyzed in March 2012.
      RESULTS: The survey sample included 1089 men without a history of prostate
      cancer. After reviewing the recommendation, 62% agreed with the recommendation.
      Age and worry about getting prostate cancer were significantly related to
      disagreement with the recommendation. Only 13% of respondents were intenders
      (they planned to follow the U.S. Preventive Services Task Force recommendation
      and not get a prostate-specific antigen test in the future); 54% were non
      intenders (they planned to not follow the U.S. Preventive Services Task Force
      recommendation and get a prostate-specific antigen test in the future; and 33%
      were undecided. Black race, higher income, having a PSA test in the past 2 years,
      and being somewhat/very worried about getting prostate cancer were all positively
      associated with being a non-intender. CONCLUSIONS: Study findings suggest that
      consumers are favorably disposed to PSA testing, despite new evidence suggesting
      that the harms outweigh the benefits. The new USPSTF recommendation against PSA
      testing in all men may be met with resistance.

PMID- 23867026
TI  - Community-level text messaging for 2009 H1N1 prevention in China.
AB  - BACKGROUND: Although patients worldwide increasingly are using mobile phone text
      messaging (SMS) for clinical care, quality data are sparse on the community-level
      effectiveness of SMS to prevent and control disease. PURPOSE: To determine SMS
      effectiveness in improving 2009 H1N1 knowledge, attitudes, behaviors, and self
      reported outcomes and to assess community SMS acceptability. METHODS: A program
      evaluation of Shanghai, China's SMS system using a single-blinded, randomized
      controlled method was conducted in 2010 and results were analyzed in 2010-2011.
      Randomly selected community residents who agreed to participate were assigned to
      receive 3 weeks of either 2009 H1N1 prevention and control or tobacco-cessation
      messages. Assessments were made of 2009 H1N1 knowledge, attitudes, behaviors, and
      self-reported influenza-like illness before and after sending messages to
      participants. Acceptability of SMS also was assessed. RESULTS: Of 1992
      respondents, those receiving 2009 H1N1 messages had higher scores measuring 2009
      H1N1 knowledge (4.2% higher) and desired attitudes (9.4% higher) (p<0.001); 1.77
      times greater odds of new 2009 H1N1 vaccination (p<0.001); and 0.12 times smaller
      odds of reporting influenza-like illness (p<0.001) than those receiving tobacco
      messages. More than 95% of participants found the SMS program useful and
      trustworthy; nearly 90% would use it again. CONCLUSIONS: SMS can improve self
      reported uptake of short-term behaviors, such as vaccination, that can result in
      long-term prevention and control of disease. SMS can improve knowledge and
      influence attitudes about infection prevention and control and self-reported
      health outcomes. In Shanghai, health-based SMS is acceptable to users.

PMID- 23867027
TI  - Infant birth weight and maltreatment of adolescent mothers.
AB  - BACKGROUND: Emerging literature suggests that maternal exposure to stress and
      adversity throughout the life course may have health consequences for offspring.
      PURPOSE: To examine the maltreatment history of adolescent mothers as an
      independent predictor of infant birth weight. METHODS: Birth records for all
      infants born between 2007 and 2009 to mothers aged 12-19 years were extracted
      from California's vital statistics files. Maternal information from the birth
      record was linked to child protection data (1999-2009) to identify young mothers
      with substantiated maltreatment. Generalized linear models run in 2012 were used
      to estimate the relationship between maternal maltreatment and infant birth
      weight, after adjusting for maternal sociodemographic risk factors and health
      behaviors. RESULTS: Among the 153,762 singleton infants born to adolescent
      mothers, 7.1% (n=10,886) weighed <2500 g at birth. Of all adolescent mothers,
      13.6% had been substantiated as victims of maltreatment after age 10 years and
      before giving birth. After adjusting for known factors predictive of negative
      birth outcomes, maltreatment history was associated with a slight yet
      significantly increased risk of low birth weight among infants (risk ratio=1.06,
      95% CI=1.01, 1.12). CONCLUSIONS: Findings from this study suggest that
      maltreatment history of adolescent mothers is associated with infant low birth
      weight (<2500 g). Although the increased risk was small and the mechanism
      unclear, these data indicate that maternal maltreatment not only may have
      consequences for the victim but also may contribute to intergenerational health
      disparities.

PMID- 23867028
TI  - Walk Score(r): associations with purposive walking in recent Cuban immigrants.
AB  - BACKGROUND: Walk Score(r) is a nationally and publicly available metric of
      neighborhood walkability based on proximity to amenities (e.g., retail, food,
      schools). However, few studies have examined the relationship of Walk Score to
      walking behavior. PURPOSE: To examine the relationship of Walk Score to walking
      behavior in a sample of recent Cuban immigrants, who overwhelmingly report little
      choice in their selection of neighborhood built environments when they arrive in
      the U.S. METHODS: Participants were 391 recent healthy Cuban immigrants (mean
      age=37.1 years) recruited within 90 days of arrival in the U.S., and assessed
      within 4 months of arrival (mean=41.0 days in the U.S.), who resided throughout
      Miami-Dade County FL. Data on participants' addresses, walking, and
      sociodemographics were collected prospectively from 2008 to 2010. Analyses
      conducted in 2011 examined the relationship of Walk Score for each participant's
      residential address in the U.S. to purposive walking, controlling for age,
      gender, education, BMI, days in the U.S., and habitual physical activity level in
      Cuba. RESULTS: For each 10-point increase in Walk Score, adjusting for
      covariates, there was a significant 19% increase in the likelihood of purposive
      walking, a 26% increase in the likelihood of meeting physical activity
      recommendations by walking, and 27% more minutes walked in the previous week.
      CONCLUSIONS: Results suggest that Walk Score is associated with walking in a
      sample of recent immigrants who initially had little choice in where they lived
      in the U.S. These results support existing guidelines indicating that mixed land
      use (such as parks and restaurants near homes) should be included when designing
      walkable communities.

PMID- 23867029
TI  - Lifestyle interventions in patients with coronary heart disease: a systematic
      review.
AB  - CONTEXT: Coronary heart disease (CHD) is responsible for about 15% of all deaths
      worldwide and is identified as a top priority for decision makers. Both primary
      and secondary prevention are considered key strategies in the prevention of CHD.
      The aim of this study was to assess the efficacy of nonpharmacologic
      interventions with multiple lifestyle components in patients with established CHD
      in comparison to usual care. For this reason, a systematic review and meta
      analysis of RCTs were performed. EVIDENCE ACQUISITION: The Cochrane Library,
      MEDLINE, and EMBASE databases were examined until March 31, 2012 (without start
      date) in order to identify studies addressing patient-tailored multifactorial
      lifestyle interventions aimed at reducing more than one cardiovascular risk
      factor in patients with established CHD. Primary endpoints were fatal and
      nonfatal cardiovascular events. Secondary outcomes were overall mortality and
      cardiovascular disease-associated hospital readmissions. EVIDENCE SYNTHESIS: The
      search strategy yielded 14 unique RCTs, which were considered in the qualitative
      analysis. Nine of them contributed to the meta-analysis. A random effects model
      was used to pool the data. The meta-analysis showed a significant risk reduction
      of 18% (relative risk 0.82, 95% CI=0.69, 0.98) of fatal cardiovascular events in
      patients undergoing multifactorial lifestyle interventions. Further, a
      nonsignificant reduction of nonfatal events, overall mortality and hospital
      readmissions was found. CONCLUSIONS: Multifactorial lifestyle interventions aimed
      at improving modifiable risk factors in patients with established CHD reduce the
      risk for fatal cardiovascular events. Therefore, they may have added value in
      secondary prevention of CHD.

PMID- 23867030
TI  - Physical activity, sedentary behavior, and postnatal depressive symptoms: a
      review.
AB  - CONTEXT: Postnatal depression is highly prevalent in mothers. Although physical
      activity has been found to reduce the risk of depression in the general
      population, little is known regarding its link with postnatal depression. This
      review examined original research investigating the relationship between physical
      activity and sedentary behavior dose (frequency, intensity, and duration) and
      domain, and postnatal depressive symptoms. EVIDENCE ACQUISITION: A systematic
      search for original research investigating the relationship between physical
      activity and sedentary behavior dose and domain, and postnatal depressive
      symptoms, was performed using several electronic databases in early 2012. A total
      of ten observational and seven intervention studies were included. EVIDENCE
      SYNTHESIS: Most studies (one cross-sectional, two longitudinal, and six
      intervention studies) found an inverse association between postpartum leisure
      time physical activity (LTPA) and postnatal depressive symptoms. One longitudinal
      study found that occupational physical activity was positively associated with
      postnatal depressive symptoms. There was inconclusive evidence to suggest an
      optimal dose of postpartum physical activity for reducing postnatal depressive
      symptoms. Two longitudinal studies found an inverse association between antenatal
      LTPA and presence of postnatal depressive symptoms. One of two studies that
      investigated sedentary behavior found a positive cross-sectional association
      between sedentary behavior and presence of postnatal depressive symptoms.
      CONCLUSIONS: Although studies are limited, on balance, LTPA prior to, during, and
      after pregnancy may be important for reducing the risk of postnatal depression.
      Further research is required to determine the optimal dose and domain of physical
      activity for reducing postnatal depressive symptoms as well as to examine the
      link between sedentary behavior and postnatal depressive symptoms.

PMID- 23867031
TI  - Mobile health technology evaluation: the mHealth evidence workshop.
AB  - Creative use of new mobile and wearable health information and sensing
      technologies (mHealth) has the potential to reduce the cost of health care and
      improve well-being in numerous ways. These applications are being developed in a
      variety of domains, but rigorous research is needed to examine the potential, as
      well as the challenges, of utilizing mobile technologies to improve health
      outcomes. Currently, evidence is sparse for the efficacy of mHealth. Although
      these technologies may be appealing and seemingly innocuous, research is needed
      to assess when, where, and for whom mHealth devices, apps, and systems are
      efficacious. In order to outline an approach to evidence generation in the field
      of mHealth that would ensure research is conducted on a rigorous empirical and
      theoretic foundation, on August 16, 2011, researchers gathered for the mHealth
      Evidence Workshop at NIH. The current paper presents the results of the workshop.
      Although the discussions at the meeting were cross-cutting, the areas covered can
      be categorized broadly into three areas: (1) evaluating assessments; (2)
      evaluating interventions; and (3) reshaping evidence generation using mHealth.
      This paper brings these concepts together to describe current evaluation
      standards, discuss future possibilities, and set a grand goal for the emerging
      field of mHealth research. 

PMID- 23867032
TI  - Pragmatic measures: what they are and why we need them.
AB  - Pragmatic measures are important to facilitate implementation and dissemination,
      address stakeholder issues, and drive quality improvement. This paper proposes
      necessary and recommended criteria for pragmatic measures, provides examples of
      projects to develop and identify such measures, addresses potential concerns
      about these recommendations, and identifies areas for future research and
      application. Key criteria for pragmatic measures include importance to
      stakeholders in addition to researchers, low burden, broad applicability,
      sensitivity to change, and being actionable. Examples of pragmatic measures are
      provided, including ones for different settings (e.g., primary care, hospital)
      and levels (e.g., individual, practitioner, setting) that illustrate approaches
      to produce broad-scale dissemination and the development of brief, standardized
      measures for use in pragmatic studies. There is an important need for pragmatic
      measures to facilitate pragmatic research, guide quality improvement, and inform
      progress on public health goals, but few examples are currently available.
      Development and evaluation of pragmatic measures and metrics would provide useful
      resources to advance science, policy, and practice. 

PMID- 23867033
TI  - What's your Walk Score(r)?: Web-based neighborhood walkability assessment for
      health promotion and disease prevention.

PMID- 23867034
TI  - U.S. Preventive Services Task Force criteria for diabetes screening: time to
      revisit the evidence?

PMID- 23867035
TI  - The times they (may) be a-changin': too much screening is a health problem.

PMID- 23867036
TI  - Adolescent obesity and risky sexual behavior.

PMID- 23867037
TI  - Evidence for community-based approaches to weight loss: a case for revising the
      Centers for Medicaid and Medicare Services reimbursement structures.

PMID- 23867038
TI  - The caloric calculator: average caloric impact of childhood obesity
      interventions.
AB  - BACKGROUND: The childhood obesity epidemic reflects the daily accumulation of an
      "energy gap"-excess calories consumed over calories expended. Population-level
      interventions to reverse the epidemic can be assessed by the degree to which they
      increase energy expenditure and/or reduce caloric intake. However, no common
      metric exists for such comparative assessment. PURPOSE: To develop a common
      metric, the Average Caloric Impact (ACI), for estimating and comparing population
      level effect sizes of a range of childhood obesity interventions. METHODS: An
      iterative, collaborative process was used to review literature from 1996 to 2012
      and select illustrative interventions showing effects on youth diet and/or
      activity levels, energy balance, and weight. The ACIs of physical activity
      interventions were estimated based on program reach, frequency, duration, and
      intensity and mean body weight of the targeted age and gender group from the 2009
      2010 National Health and Nutrition Examination Survey. ACIs of dietary
      interventions were based on reach and changes in foods and/or beverages consumed.
      RESULTS: Fifteen interventions informed by 29 studies were included, ranging from
      individual behavioral to population-level policies. A web tool, the Caloric
      Calculator, was developed to allow researchers and policymakers to estimate the
      ACIs of interventions on target populations with reference to energy gap
      reductions required to reach the nation's Healthy People childhood obesity goals.
      CONCLUSIONS: The Caloric Calculator and ACIs provide researchers and policymakers
      with a common metric for estimating the potential effect sizes of various
      interventions for reducing childhood obesity, providing a platform for evidence
      based dialogues on new program or policy approaches as data emerge.

PMID- 23867039
TI  - A proposal for the classification of etiologies of neurologic deterioration after
      acute ischemic stroke.
AB  - BACKGROUND: Neurologic deterioration (ND) occurs in one third of patients with
      ischemic stroke and contributes to morbidity and mortality in these patients.
      Etiologies of ND and clinical outcome according to ND etiology are incompletely
      understood. METHODS: We conducted a retrospective investigation of all patients
      with ischemic stroke admitted to our center (July 2008 to December 2010), who
      were known to be last seen normal less than 48 hours before arrival. First-time
      episodes of ND during hospitalization were collected in which a patient
      experienced a 2-point increase or more in National Institutes of Health Stroke
      Scale score within a 24-hour period. Proposed etiologies of reversible ND include
      infectious, metabolic, hemodynamic, focal cerebral edema, fluctuation, sedation,
      and seizure, whereas new stroke, progressive stroke, intracerebral hemorrhage,
      and cardiopulmonary arrest were nonreversible. RESULTS: Of 366 included patients
      (median age 65 years, 41.4% women, 68.3% black), 128 (34.9%) experienced ND
      (median age 69 years, 42.2% women, 68.7% black). Probable etiologies of ND were
      identified in 90.6% of all first-time ND events. The most common etiology of ND,
      progressive stroke, was highly associated with poor outcome but not death.
      Etiologies most associated with mortality included edema (47.8%), new stroke
      (50%), and intracerebral hemorrhage (42.1%). CONCLUSIONS: In the present study,
      the authors identified probable etiologies of ND after ischemic stroke.
      Delineating the cause of ND could play an important role in the management of the
      patient and help set expectations for prognosis after ND has occurred.
      Prospective studies are needed to validate these proposed definitions of ND.

PMID- 23867040
TI  - Effect of functional electrical stimulation with mirror therapy on upper
      extremity motor function in poststroke patients.
AB  - BACKGROUND: Motor recovery of the upper extremity in stroke patients is an
      important goal of rehabilitation. In particular, motor recovery can be
      accelerated when physical and cognitive interventions are combined. Thus, the aim
      of this study was to investigate the effects of functional electrical stimulation
      (FES) with mirror therapy (MT) on motor function of upper extremity in stroke
      patients. METHODS: Twenty-seven stroke patients were recruited, and the 23
      subjects who met the inclusion criteria were randomly allocated into 2 groups:
      the experimental group (n = 12) and the control group (n = 11). Both groups
      received conventional rehabilitation training for 60 minutes/day and 5 days/week
      for 4 weeks. In addition, members of the experimental group received FES with MT
      and members of the control group received FES without MT for 30 minutes/day and 5
      days/week for 4 weeks. Immediately before and after intervention, motor recovery
      was measured using the Fugl-Meyer (FM) assessment, Brunnstrom's motor recovery
      stage (BMRS), the Manual Function Test (MFT), and the Box and Block Test (BBT).
      RESULTS: Significant upper extremity motor improvements were observed in the
      experimental and control groups according to the FM, BMRS, MFT, and BBT (P <
      .05). In particular, FM subscores for wrist, hand, and co-ordination and MFT
      subscores for hand function were more significantly improved in the experimental
      group (P < .05). CONCLUSIONS: Motor functions of the upper extremity were
      improved by FES with MT versus controls. The study shows that FES with MT during
      poststroke rehabilitation may effectively improve motor functions of the upper
      extremity.

PMID- 23867041
TI  - Long-term improvement in outcome after intracerebral hemorrhage in patients
      treated with statins.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is a severe type of stroke for which
      there is currently no specific medical therapy. We hypothesized that statins
      reduce immediate inflammatory injury and improve long-term recovery from
      increased neurogenesis and angiogenesis. We conducted a large retrospective
      cohort study to assess the influence of statin therapy on patient death and
      disability at 12 months after ICH. METHODS: This was a retrospective analysis of
      a prospectively collected database at a tertiary care medical center. Patients
      were grouped based on statin use, and poor outcome was assessed as dead or alive
      with dependency (modified Barthel Index<=14). RESULTS: We compared outcomes in
      190 patients exposed to statins to 236 patients who were not exposed to statins.
      Univariate analysis found that statin use was associated with decreased mortality
      in-hospital and at 12 months (P=.001). Multivariable analysis found that statin
      use was associated with a decreased odds of death or disability at 12 months
      after ICH (odds ratio 0.44; 95% confidence interval 0.21-0.95). CONCLUSIONS:
      Statin use is associated with improved long-term outcome at 12 months after ICH.
      This finding supports previous clinical studies that have shown the short-term
      benefits of statin therapy. In addition, this study correlates with animal
      studies supporting the possible long-term recovery benefits of statins.

PMID- 23867042
TI  - Response to the letter by Kazuo Yamashiro.

PMID- 23867043
TI  - Recurrent ischemic stroke in an adult with cystinosis: a clinical-pathological
      case.
AB  - A 32-year-old woman with infantile nephropathic cystinosis presented with
      cystinosis and recurrent ischemic stroke. The neuropathological description
      demonstrates that recurrent stroke was caused by intracranial stenosis and showed
      evidence of cystinosis brain involvement. There are few reports of
      cerebrovascular disease in patients with longstanding nephropathic cystinosis.
      This case reinforces that cerebrovascular disease can be a cause of neurological
      impairment and disability in patients with longstanding nephropathic cystinosis,
      with implications on primary stroke prevention strategies in these patients. 

PMID- 23867044
TI  - Effects of carotid endarterectomy or stenting on arterial diameters in the circle
      of Willis.
AB  - BACKGROUND: In patients with internal carotid artery (ICA) stenosis, the circle
      of Willis (CoW) is the primary collateral pathway. We compared luminal diameters
      in the CoW before and after carotid revascularization and compared the effects of
      carotid endarterectomy (CEA) and stenting on these diameters. METHODS: At a
      single center in the International Carotid Stenting Study, 139 patients with
      symptomatic ICA stenosis of 50% or more were randomized to stenting (n = 81) or
      CEA (n = 58). The diameters of all segments of the CoW were assessed on computed
      tomography angiography (CTA), before and 30 days after revascularization. All
      evaluations were performed blinded to treatment allocation and order of CTA.
      RESULTS: A .10-mm increase (95% confidence interval [CI], .02-.17; 7%; P = .01)
      in diameter after revascularization occurred in the ipsilateral precommunicating
      anterior cerebral artery (A1), whereas both the ipsilateral and contralateral
      posterior communicating arteries decreased in diameter by .12 mm (95% CI, .04
      .21; 14%; P = .01) and .08 mm (95% CI, .00-.17; 10%; P = .05), respectively. The
      increase in diameter of the A1 was larger after stenting (.15 mm; 95% CI, .07
      .24; P = .001) than after CEA (.02 mm; 95% CI, -.11 to .15; P = .79). Only in
      patients treated with CEA, the diameters of the contralateral A1 and ipsilateral
      precommunicating posterior cerebral artery were reduced after revascularization.
      CONCLUSIONS: Carotid revascularization improves anterior collateralization and
      reduces reliance on posterior collateral pathways via the CoW. Carotid stenting
      and endarterectomy appear to have different early effects on collateralization.

PMID- 23867046
TI  - The role of the media in the science-policy nexus. Some critical reflections
      based on an analysis of the Belgian drug policy debate (1996-2003).
AB  - BACKGROUND: Drug policy is one of the most polarised subjects of public debate
      and media coverage, which frequently tend to be dramatic and event-centred.
      Although the role of the media in directing the drug discourse is widely
      acknowledged, limited research has been conducted in examining the particular
      role of the media in the science-policy nexus. We sought to determine how the
      (mis)representation of scientific knowledge in the media may, or may not, have an
      impact on the contribution of scientific knowledge to the drug-policy making
      process. METHODS: Using a case study of the Belgian drug-policy debates between
      1996 and 2003, we conducted a discourse analysis of specially selected 1067
      newspaper articles and 164 policy documents. Our analysis focused on: textual
      elements that feature intra-discourse differences, how players and scientific
      knowledge are represented in the text, the arguments used and claims made, and
      the various types of research utilisation. RESULTS: Media discourse strongly
      influenced the public's and policy makers' understanding as well as the content
      of the Belgian drug policy debate between 1996 and 2003. As a major source of
      scientific knowledge, media coverage supported the 'enlightenment' role of
      scientific knowledge in the policy-making process by broadening and even
      determining frames of reference. However, as the presentation of scientific
      knowledge in the media was often inaccurate or distorted due to the lack of
      contextual information or statistical misinformation, the media may also support
      the selective utilisation of scientific knowledge. CONCLUSIONS: Many challenges
      as well as opportunities lie ahead for researchers who want to influence the
      policy-making process since most research fails to go beyond academic
      publications. Although media is a valuable linking mechanism between science and
      policy, by no means does it provide scientists with a guarantee of a more
      'evidence-based' drug policy.

PMID- 23867045
TI  - A new classification system for ischemia using a combination of deep and
      periventricular white matter hyperintensities.
AB  - The Clinical Research Center for Dementia of South Korea (CREDOS) group developed
      a new classification system for ischemia using a combination of deep and
      periventricular white matter hyperintensities (WMHs). In this study, we aimed to
      evaluate the validity of the CREDOS ischemia classification system. A total of
      352 patients with cognitive impairments were included. Their WMH scores were
      rated using the CREDOS WMH visual rating scale. These patients were divided into
      3 groups according to the CREDOS ischemia classification system. The volume of
      WMH was also automatically measured. The number of lacunes and microbleeds (MBs)
      were counted. The CREDOS ischemia classification system was revised with factor
      analysis using vascular risk factors and cerebrovascular disease (CVD) markers
      (WMH volume, lacunes, and MBs). External validation was performed in another
      group of patients with cognitive impairment using multinomial logistic regression
      analysis. The CREDOS WMH visual rating scale showed excellent correlation with
      the automatically measured volume of WMH. The factor analysis showed that the
      severe group was expanded to D3P1 and D3P2 in the revised CREDOS ischemia
      classification system. In the validation group, the presence of vascular risk
      factors and the severity of CVD markers could be distinguished according to the
      revised CREDOS ischemia classification. We validated a newly developed
      classification system for ischemia. This simple visual classification system was
      capable of providing information on vascular risk factors and CVD markers by
      simply rating WMH on magnetic resonance imaging. 

PMID- 23867047
TI  - Preventing alcohol harm: early results from a cluster randomised, controlled
      trial in Victoria, Australia of comprehensive harm minimisation school drug
      education.
AB  - BACKGROUND: In Australia, the burden of alcohol-attributable harm falls most
      heavily on young people. Prevention is important, and schools have long been seen
      as appropriate settings for pre-emptive interventions with this high risk group.
      This paper evaluates the effectiveness, in relation to alcohol harm prevention,
      of the Drug Education in Victorian Schools (DEVS) programme, nine months after
      implementation. This intervention dealt with both licit and illicit drugs,
      employed a harm minimisation approach that incorporated interactive, skill based,
      teaching methods and capitalised on parental influence through home activities.
      METHODS: A cluster randomised, controlled trial of the first ten lessons of the
      DEVS drug education programme was conducted with year eight students, aged 13-14
      years. Twenty-one secondary schools in Victoria, Australia were randomly
      allocated to receive the DEVS programme (14 schools, n=1163) or the drug
      education usually provided by their schools (7 schools, n=589). Self-reported
      changes were measured in relation to: knowledge and attitudes, communication with
      parents, drug education lessons remembered, proportion of drinkers, alcohol
      consumption (quantity multiplied by frequency), proportion of student drinkers
      engaging in risky consumption, and the number of harms experienced as a result of
      alcohol consumption. RESULTS: In comparison to the controls, there was a
      significantly greater increase in the intervention students' knowledge about
      drugs, including alcohol (p<=0.001); there was a significant change in their
      level of communication with parents about alcohol (p=0.037); they recalled
      receiving significantly more alcohol education (p<0.001); their alcohol
      consumption increased significantly less (p=0.011); and they experienced a lesser
      increase in harms associated with their drinking (p<=0.001). There were no
      significant differences between the two study groups in relation to changes in
      attitudes towards alcohol or in the proportion of drinkers or risky drinkers.
      There was, however, a notable trend of less consumption by risky drinkers in the
      intervention group. CONCLUSIONS: A comprehensive, harm minimisation focused
      school drug education programme is effective in increasing general drug
      knowledge, and reducing alcohol consumption and harm.

PMID- 23867048
TI  - Building partnerships between law enforcement and harm reduction programs.

PMID- 23867049
TI  - "Everyone can loosen up and get a bit of a buzz on": young adults, alcohol and
      friendship practices.
AB  - In countries with liberalised alcohol policies, alcohol harm reduction strategies
      predominantly focus on young adults' excessive drinking harms and risks. However,
      research shows such risks are largely irrelevant for young adults, who emphasise
      the sociability, release, pleasure and fun of drinking. Friendship is a central
      part of their lives and an integral part of their drinking experiences. This
      study aimed to explore everyday friendship practices, drinking, and pleasure in
      young people's routine and shared social lives. Twelve friendship discussion
      groups were conducted in urban and non-urban New Zealand, with 26 women and 25
      men aged 18-25 years. Our Foucauldian discursive analysis enabled us to identify
      how the young adults drew on drinking as 'friendship fun' and 'friends with a
      buzz' discourses to construct drinking as a pleasurable and socially embodied
      friendship practice. Yet the young adults also drew on 'good always outweighs bad
      experiences' and friendship 'caring and protection' discourses to smooth over
      disruptive negative drinking experiences. Together these discourses function to
      justify young adults' drinking as friendship pleasure, minimising alcohol harms,
      and setting up powerful resistances to individualised risk-based alcohol-harm
      reduction campaigns. These findings are discussed in terms of new insights and
      implications for alcohol harm reduction strategies that target young adults. 

PMID- 23867050
TI  - An exploration of self-perceived non-problematic use as a barrier to professional
      support for methamphetamine users.

PMID- 23867051
TI  - Effect of reclassification of cannabis on hospital admissions for cannabis
      psychosis: a time series analysis.
AB  - BACKGROUND: The UK Misuse of Drugs Act (1971) divided controlled drugs into three
      groups A, B and C, with descending criminal sanctions attached to each class.
      Cannabis was originally assigned by the Act to Group B but in 2004, it was
      transferred to the lowest risk group, Group C. Then in 2009, on the basis of
      increasing concerns about a link between high strength cannabis and
      schizophrenia, it was moved back to Group B. The aim of this study is to test the
      assumption that changes in classification lead to changes in levels of psychosis.
      In particular, it explores whether the two changes in 2004 and 2009 were
      associated with changes in the numbers of people admitted for cannabis psychosis.
      METHOD: An interrupted time series was used to investigate the relationship
      between the two changes in cannabis classification and their impact on hospital
      admissions for cannabis psychosis. Reflecting the two policy changes, two
      interruptions to the time series were made. Hospital Episode Statistics
      admissions data was analysed covering the period 1999 through to 2010. RESULTS:
      There was a significantly increasing trend in cannabis psychosis admissions from
      1999 to 2004. However, following the reclassification of cannabis from B to C in
      2004, there was a significant change in the trend such that cannabis psychosis
      admissions declined to 2009. Following the second reclassification of cannabis
      back to class B in 2009, there was a significant change to increasing admissions.
      CONCLUSION: This study shows a statistical association between the
      reclassification of cannabis and hospital admissions for cannabis psychosis in
      the opposite direction to that predicted by the presumed relationship between the
      two. However, the reasons for this statistical association are unclear. It is
      unlikely to be due to changes in cannabis use over this period. Other possible
      explanations include changes in policing and systemic changes in mental health
      services unrelated to classification decisions.

PMID- 23867052
TI  - Methods for serial analysis of long time series in the study of biological
      rhythms.
AB  - When one is faced with the analysis of long time series, one often finds that the
      characteristics of circadian rhythms vary with time throughout the series. To
      cope with this situation, the whole series can be fragmented into successive
      sections which are analyzed one after the other, which constitutes a serial
      analysis. This article discusses serial analysis techniques, beginning with the
      characteristics that the sections must have and how they can affect the results.
      After consideration of the effects of some simple filters, different types of
      serial analysis are discussed systematically according to the variable analyzed
      or the estimated parameters: scalar magnitudes, angular magnitudes (time or
      phase), magnitudes related to frequencies (or periods), periodograms, and derived
      and / or special magnitudes and variables. The use of wavelet analysis and
      convolutions in long time series is also discussed. In all cases the fundamentals
      of each method are exposed, jointly with practical considerations and graphic
      examples. The final section provides information about software available to
      perform this type of analysis. 

PMID- 23867053
TI  - Antidepressant and group psychosocial treatment for depression: a rater blind
      exploratory RCT from a low income country.
AB  - BACKGROUND: Research in the West shows that group psychological intervention
      together with an antidepressant treatment leads to more effective treatment of a
      depressive disorder. There are no treatment trials from low income countries
      comparing the efficacy of antidepressant treatment with a group psychological
      intervention. AIM: To conduct a feasibility trial to compare the efficacy of an
      antidepressant to a group psychosocial intervention, for low income women
      attending primary health care in Karachi, Pakistan. METHOD: This was a
      preliminary RCT in an urban primary health care clinic in Karachi, Pakistan.
      Consecutive eligible women scoring >12 on the CIS-R and >18 on Hamilton
      Depression Rating Scale (HDRS) (n = 66) were randomly assigned to antidepressants
      or a psychosocial treatment in group settings. The primary outcome measure was
      HDRS score; secondary outcome measures were disability and quality of life.
      RESULTS: More than half of the patients in both groups improved (50% reduction in
      HDRS scores); at end of therapy at 3 months 19 (59.4%) vs 18 (56.2%), and at 6
      month follow-up 21(67.7%) vs 20(62.5%) for antidepressants and psychosocial
      intervention respectively. Although HDRS, BDQ and EQ5-D scores all improved
      considerably in both groups from start to end of treatment, and these
      improvements were largely maintained after a further 3 months, the differences
      between the two treatments were not statistically significant. CONCLUSION:
      Psychosocial intervention was as effective as antidepressants in reducing
      depression and in improving quality of life and disability at the end of therapy.
      However, these findings need further exploration through a larger trial.

PMID- 23867054
TI  - Position statement on tobacco exposures in children and families.

PMID- 23867055
TI  - Childhood constipation in the emergency department.

PMID- 23867056
TI  - beta-Catenin and AKT are promising targets for combination therapy in acute
      myeloid leukemia.
AB  - In this study, we confirmed that combining HHT with ACR can result in synergistic
      cytotoxicity to AML cells in vitro and in vivo. Combining HHT and ACR
      simultaneously inhibited PI3K/AKT and WNT/beta-catenin signaling in AML cells.
      Significant increases in growth inhibition and apoptosis were induced by an AKT
      inhibitor when the WNT3A gene of THP-1 cells was silenced. HHT+ACR could
      synergistically induce the apoptosis of CD34(+)/CD38(-) primary AML cells. These
      results highlight beta-catenin and AKT are promising targets for combination
      therapy for AML. 

PMID- 23867057
TI  - Differential survival improvement for patients 20-29 years of age with acute
      lymphoblastic leukemia.
AB  - OBJECTIVE: To compare improvement in survival from 1986 to 2009 for acute
      lymphoblastic leukemia (ALL) patients 1-14, 15-19 and 20-29 years in Ontario and
      United States. METHODS: This population-based analysis used data from Ontario
      Cancer Registry (OCR) and Surveillance Epidemiology and End Results (SEER).
      RESULTS: In OCR, there was steady improvement in survival by period of diagnosis
      in all three age groups. In SEER, there was no improvement in survival for
      patients aged 20-29 years. CONCLUSIONS: Survival in Ontario and the United States
      has improved for patients with ALL aged 1-19 years. However, survival has
      improved among patients aged 20-29 years only in Ontario.

PMID- 23867059
TI  - Youth bullying: a review of the science and call to action.
AB  - Recognized as a critical public health problem, youth bullying is reportedly
      experienced by approximately 20% of today's youths. In the last decade, attention
      to bullying has increased and the scientific knowledge base relevant for
      practitioners who treat youths, research their issues, and create policy has
      expanded. The purpose of this review is to highlight key developments related to
      the health effects of bullying, interventions aimed at curbing bullying
      behaviors, the measurement of bullying, and nursing's disciplinary response to
      this phenomenon. A call to action for nurses involved in caring for youths across
      settings and roles is offered and strategic actions for nursing professionals are
      provided.

PMID- 23867058
TI  - Cyclophosphamide, alvocidib (flavopiridol), and rituximab, a novel feasible
      chemoimmunotherapy regimen for patients with high-risk chronic lymphocytic
      leukemia.
AB  - Alvocidib has demonstrated efficacy in high-risk chronic lymphocytic leukemia
      (CLL) patients. In this phase I study, we combined cyclophosphamide, alvocidib
      and rituximab (CAR) in a schema designed to mitigate tumor lysis syndrome (TLS)
      seen previously with alvocidib. Nine nucleoside analog-naive, high-risk patients
      received escalating doses of CAR therapy. Dose limiting toxicity was not
      experienced. No instances of TLS were observed. Patient responses included three
      complete remissions and four partial remissions. CAR was tolerable and active in
      high-risk CLL patients without TLS toxicity. With continued monitoring of
      toxicities, a phase Ib/II study of this combination as frontline therapy is
      warranted. 

PMID- 23867060
TI  - Vaccination of ferrets with a recombinant G glycoprotein subunit vaccine provides
      protection against Nipah virus disease for over 12 months.
AB  - BACKGROUND: Nipah virus (NiV) is a zoonotic virus belonging to the henipavirus
      genus in the family Paramyxoviridae. Since NiV was first identified in 1999,
      outbreaks have continued to occur in humans in Bangladesh and India on an almost
      annual basis with case fatality rates reported between 40% and 100%. METHODS:
      Ferrets were vaccinated with 4, 20 or 100 MUg HeVsG formulated with the human use
      approved adjuvant, CpG, in a prime-boost regime. One half of the ferrets were
      exposed to NiV at 20 days post boost vaccination and the other at 434 days post
      vaccination. The presence of virus or viral genome was assessed in ferret fluids
      and tissues using real-time PCR, virus isolation, histopathology, and
      immunohistochemistry; serology was also carried out. Non-immunised ferrets were
      also exposed to virus to confirm the pathogenicity of the inoculum. RESULTS:
      Ferrets exposed to Nipah virus 20 days post vaccination remained clinically
      healthy. Virus or viral genome was not detected in any tissues or fluids of the
      vaccinated ferrets; lesions and antigen were not identified on immunohistological
      examination of tissues; and there was no increase in antibody titre during the
      observation period, consistent with failure of virus replication. Of the ferrets
      challenged 434 days post vaccination, all five remained well throughout the study
      period; viral genome - but not virus - was recovered from nasal secretions of one
      ferret given 20 MUg HeVsG and bronchial lymph nodes of the other. There was no
      increase in antibody titre during the observation period, consistent with lack of
      stimulation of a humoral memory response. CONCLUSIONS: We have previously shown
      that ferrets vaccinated with 4, 20 or 100 MUg HeVsG formulated with CpG adjuvant,
      which is currently in several human clinical trials, were protected from HeV
      disease. Here we show, under similar conditions of use, that the vaccine also
      provides protection against NiV-induced disease. Such protection persists for at
      least 12 months post-vaccination, with data supporting only localised and self
      limiting virus replication in 2 of 5 animals. These results augur well for
      acceptability of the vaccine to industry.

PMID- 23867061
TI  - Changes in fibrinogen availability and utilization in an animal model of
      traumatic coagulopathy.
AB  - BACKGROUND: Impaired haemostasis following shock and tissue trauma is frequently
      detected in the trauma setting. These changes occur early, and are associated
      with increased mortality. The mechanism behind trauma-induced coagulopathy (TIC)
      is not clear. Several studies highlight the crucial role of fibrinogen in
      posttraumatic haemorrhage. This study explores the coagulation changes in a swine
      model of early TIC, with emphasis on fibrinogen levels and utilization of
      fibrinogen. METHODS: A total of 18 landrace pigs were anaesthetized and divided
      into four groups. The Trauma-Shock group (TS) were inflicted bilateral blast
      femoral fractures with concomitant soft tissue injury by a high-energy rifle shot
      to both hind legs, followed by controlled exsanguination. The Shock group (S) was
      exposed to shock by exsanguination, whereas a third group was exposed to trauma
      only (T). A fourth group (C) served as control. Physiological data,
      haematological measurements, blood gas analyses and conventional coagulation
      assays were recorded at baseline and repeatedly over 60 minutes.
      Thrombelastometry were performed by means of the tissue factor activated ExTEM
      assay and the platelet inhibiting FibTEM assay. Data were statistically analysed
      by repeated measurements analyses method. RESULTS: A significant reduction of
      fibrinogen concentration was observed in both the TS and S groups. INR increased
      significantly in the S group and differed significantly from the TS group.
      Maximum clot firmness (MCF) of the ExTEM assay was significantly reduced over
      time in both TS and S groups. In the FibTEM assay a significant shortening of the
      clotting time and an increase in MCF was observed in the TS group compared to the
      S group. CONCLUSION: Despite a reduction in clotting capability measured by ExTEM
      MCF and a reduced fibrinogen concentration, extensive tissue trauma may induce an
      increased fibrin based clotting activity that attenuates the hypocoagulable
      tendency in exsanguinated animals.

PMID- 23867062
TI  - Approaches towards the synthesis of a novel class of 2-amino-5-arylazonicotinate,
      pyridazinone and pyrido[2,3-d]pyrimidine derivatives as potent antimicrobial
      agents.
AB  - BACKGROUND: Despite significant progresses in antimicrobial therapy, infectious
      diseases caused by bacteria and fungi remain a major worldwide health problem
      because of the rapid development of resistance to existing antimicrobial drugs.
      Therefore, there is a constant need for new antimicrobial agents. There are a
      large number of heterocyclic derivatives containing nitrogen atoms that possess a
      broad spectrum of biological activities including pyridine and pyridazine, which
      are two of the most important heterocycles in medicinal chemistry. RESULTS: The
      reaction of 3-oxo-2-arylhydrazonopropanals 2 with ethyl cyanoacetate and
      malononitrile 3a,b has led to the formation of 2-amino-5-arylazo-6-aryl
      substituted nicotinates 8a-k as sole isolable products when the aryl group in the
      arylazo moiety was substituted with an electron-withdrawing group like Cl, Br,
      NO2. The pyridazinones 10 were formed from the same reaction when the arylazo
      moiety was phenyl or phenyl substituted with an electron-donating group. The 2
      aminoazonicotinates 8 were condensed with DMF-DMA to afford the amidines 13a,b,
      which then were cyclized to afford the targeted pyrido[2,3-d]pyrimidine
      derivatives 15a,b, respectively. The structures of all new substances prepared in
      this investigation were determined by using X-ray crystallographic analysis and
      spectroscopic methods. Most of the synthesized compounds were tested and
      evaluated as antimicrobial agents and the results indicated that many of the
      obtained compounds exhibited high antimicrobial activity comparable to
      ampicillin, which was used as the reference compound. CONCLUSION: A general rule
      for the synthesis of 2-amino-5-arylazo-6-aryl substituted nicotinic acid and
      pyridazinone was established using 3-oxo-2-arylhydrazonopropanal as a precursor.
      Moreover, a novel route to pyrido[2,3-d]pyrimidine was achieved. Most of the
      synthesized compounds were found to exhibit strong inhibitory effects on the
      growth of Gram-positive bacteria especially Bacillus subtilis. Compounds 1a, 8a
      h, 10a-c, 15b and 16 showed a broad spectrum of antimicrobial activity against B.
      subtilis.

PMID- 23867063
TI  - Auditory post-processing in a passive listening task is deficient in Alzheimer's
      disease.
AB  - OBJECTIVE: To investigate whether automatic auditory post-processing is deficient
      in patients with Alzheimer's disease and is related to sensory gating. METHODS:
      Event-related potentials were recorded during a passive listening task to examine
      the automatic transient storage of auditory information (short click pairs).
      Patients with Alzheimer's disease were compared to a healthy age-matched control
      group. A young healthy control group was included to assess effects of
      physiological aging. RESULTS: A bilateral frontal negativity in combination with
      deep temporal positivity occurring 500 ms after stimulus offset was reduced in
      patients with Alzheimer's disease, but was unaffected by physiological aging. Its
      amplitude correlated with short-term memory capacity, but was independent of
      sensory gating in healthy elderly controls. Source analysis revealed a dipole
      pair in the anterior temporal lobes. CONCLUSION: Results suggest that auditory
      post-processing is deficient in Alzheimer's disease, but is not typically related
      to sensory gating. The deficit could neither be explained by physiological aging
      nor by problems in earlier stages of auditory perception. Correlations with short
      term memory capacity and executive control tasks suggested an association with
      memory encoding and/or overall cognitive control deficits. SIGNIFICANCE: An
      auditory late negative wave could represent a marker of auditory working memory
      encoding deficits in Alzheimer's disease.

PMID- 23867064
TI  - A new neurophysiological approach to assess central motor conduction damage to
      proximal and distal muscles of lower limbs.
AB  - OBJECTIVE: To develop a neurophysiological method to explore central motor
      pathways to proximal and distal muscles of lower limbs. METHODS: MEPs to
      transcranial magnetic stimulation using the double cone coil were bilaterally and
      simultaneously recorded from vastus medialis, tibialis anterior and flexor
      hallucis brevis. Voluntary facilitation was controlled using a predefined
      sequence of movements of constant amplitude. Compound motor action potentials
      elicited by maximal high voltage electrical stimulation of lumbosacral roots
      (root-CMAPs) were recorded from the same muscles to obtain the corresponding
      peripheral conduction times. We studied 28 healthy subjects and 28 multiple
      sclerosis (MS) patients with no or mild motor impairment. RESULTS: The described
      facilitation procedure and the averaging of 5 MEPs reduced area variability to
      about 10%. In MS patients conduction slowing and/or MEP area reduction in at
      least one muscle was found in 91.7% of cases, with significant correlation with
      individual motor impairment. CONCLUSIONS: Combined use of stable MEPs and maximal
      root-CMAPs was able to detect both conduction slowing and conduction failure in
      central motor pathways to proximal and distal districts of lower limbs in MS
      patients. SIGNIFICANCE: The proposed method provides an extensive
      electrophysiological mapping of central motor impairment of lower limbs in
      clinical application.

PMID- 23867065
TI  - Intra-rater reliability of motor unit number estimation and quantitative motor
      unit analysis in subjects with amyotrophic lateral sclerosis.
AB  - OBJECTIVES: To assess the intra-rater reliability of decomposition-enhanced spike
      triggered averaging (DE-STA) motor unit number estimation (MUNE) and quantitative
      motor unit potential analysis in the upper trapezius (UT) and biceps brachii (BB)
      of subjects with amyotrophic lateral sclerosis (ALS) and to compare the results
      from the UT to control data. METHODS: Patients diagnosed with clinically probable
      or definite ALS completed the experimental protocol twice with the same evaluator
      for the UT (n=10) and BB (n=9). RESULTS: Intra-rater reliability for the UT was
      good for the maximum compound muscle action potential (CMAP) (ICC=0.88), mean
      surface-detected motor unit potential (S-MUP) (ICC=0.87) and MUNE (ICC=0.88), and
      for the BB was moderate for maximum CMAP (ICC=0.61), and excellent for mean S-MUP
      (ICC=0.94) and MUNE (ICC=0.93). A significant difference between tests was found
      for UT MUNE. Comparing subjects with ALS to control subjects, UT maximum CMAP
      (p<0.01) and MUNE (p<0.001) values were significantly lower, and mean S-MUP
      values significantly greater (p<0.05) in subjects with ALS. CONCLUSIONS: This
      study has demonstrated the ability of the DE-STA MUNE technique to collect highly
      reliable data from two separate muscle groups and to detect the underlying
      pathophysiology of the disease. SIGNIFICANCE: This was the first study to examine
      the reliability of this technique in subjects with ALS, and demonstrates its
      potential for future use as an outcome measure in ALS clinical trials and studies
      of ALS disease severity and natural history.

PMID- 23867066
TI  - Evidence for a causal relationship between hyperkalaemia and axonal dysfunction
      in end-stage kidney disease.
AB  - OBJECTIVE: Potassium (K(+)) has been implicated as a factor in the development of
      uraemic neuropathy. This study was undertaken to investigate whether
      hyperkalaemia plays a causal role in axonal dysfunction in end-stage kidney
      disease (ESKD). METHODS: Median motor nerve excitability studies were undertaken
      in four haemodialysis patients during a modified dialysis session. The serum K(+)
      level was "clamped" (fixed) for the first 3h of dialysis, whilst allowing all
      other solutes to be removed, this was followed by dialysis against low dialysate
      K(+) for a further 4 h. Blood chemistry and nerve excitability studies were
      undertaken prior to, during and following dialysis. Results were compared to
      results from the same patients during routine dialysis sessions. RESULTS: All
      patients demonstrated significant nerve excitability abnormalities reflective of
      nerve membrane depolarization in pre-dialysis recordings (p<0.01). After the 3 h
      clamp period, serum K(+) remained elevated (5.0 mmol/L) and nerve excitability
      remained highly abnormal, despite the significant clearance of other uraemic
      toxins. In contrast, studies undertaken during routine dialysis sessions
      demonstrated significant improvement in both serum K(+) and nerve function after
      3 h. CONCLUSIONS: The current study has established a causal relationship between
      serum K(+) and axonal membrane depolarization in haemodialysis patients.
      SIGNIFICANCE: From a clinical perspective, strict K(+) control may help improve
      nerve function in ESKD.

PMID- 23867067
TI  - Monitoring in language perception in high-functioning adults with autism spectrum
      disorder: evidence from event-related potentials.
AB  - OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impaired global
      language processing, whereas local language processing often appears intact.
      Recent psycholinguistic research suggests that the quality of language perception
      relies on monitoring, an aspect of executive control. The aim of the study was to
      examine monitoring in people with ASD of (a) local, orthographic violations, and
      (b) global, syntactic violations, when provided with single level versus dual
      level task instructions. METHODS: We recorded event-related potentials and
      compared P600 effects to the linguistic violations relative to correct words in
      14 adults with ASD and 14 matched controls. RESULTS: In control participants,
      local errors elicited a monitoring response as tapped by the P600 effect in both
      conditions. For global errors, the P600 effect was present only at one
      centroposterior site in the single level condition, whereas in the dual level
      condition a broadly distributed effect was obtained. People with ASD, however,
      showed a monitoring response to local and global errors both in the single and
      dual level condition. CONCLUSIONS: The main ERP finding suggests that when
      instructed people with ASD monitor global aspects of language already under
      simple circumstances, whereas people without ASD mainly do so under more complex
      circumstances. SIGNIFICANCE: Results suggest that language problems in ASD should
      not be studied in terms of a linguistic dysfunction as such, but in light of the
      use of executive resources during language comprehension.

PMID- 23867068
TI  - Gastrointestinal tract development in red deer (Cervus elaphus) calves from 1 to
      12 months of age.
AB  - This study provides a detailed description of the development of the
      gastrointestinal tract (GIT) of farmed red deer (Cervus elaphus) calves over the
      first 12 months of age. GIT development was measured using a combination of
      computerised tomography (CT) scanning and traditional slaughter plus dissection
      techniques. Red deer calves of a known birth date were randomly assigned to two
      treatment groups. A group of five animals were repeatedly CT scanned at 31, 63,
      92, 135, 207, 275 and 351 days of age to identify GIT organs and determine their
      volume. From a group of 20 animals, subsets of four individuals were also scanned
      at corresponding ages (except 135 days of age). They were immediately euthanised
      and dissected after CT scanning to compare CT-scanned results with actual
      anatomical measurements. Individual organ weights were compared with their
      respective organ volumes determined by CT scanning and were found to have a
      strong, positive relationship. The combined rumen and reticulum (RR) CT-scanned
      volume was compared with its volume determined by the water-displacement
      technique and this also showed good correlation between the two techniques (R =
      0.92). The allometric growth rates of organs, relative to animal live weight
      gains, in descending order, were the rumen, omasum, reticulum, abomasum, caecum
      blind sac, kidneys, spleen and liver. The red deer GIT was continuing to grow and
      develop when the last measurement was taken at 351 days of age. The greatest
      growth of the RR, when expressed in terms of empty weight, was between 31 and 92
      days of age. Compared with sheep and cattle, it appears that the red deer have a
      similar or greater rate of RR development up until approximately 60 to 90 days of
      age; however, the final increments of GIT maturity in deer may take longer to
      complete, with the empty weight of the RR gaining 7.5 g/day between 275 and 351
      days of age. CT scanning was validated in this study as a viable technique to
      follow GIT development in the same animals over time, and it provided novel
      information on allometric organ growth. The success of CT scanning highlights the
      potential future use of diagnostic imaging for GIT development studies. 

PMID- 23867069
TI  - Project Energize: whole-region primary school nutrition and physical activity
      programme; evaluation of body size and fitness 5 years after the randomised
      controlled trial.
AB  - Project Energize, a region-wide whole-school nutrition and physical activity
      programme, commenced as a randomised controlled trial (RCT) in the period 2004-6
      in 124 schools in Waikato, New Zealand. In 2007, sixty-two control schools were
      engaged in the programme, and by 2011, all but two of the 235 schools in the
      region were engaged. Energizers (trained nutrition and physical activity
      specialists) work with eight to twelve schools each to achieve the goals of the
      programme, which are based on healthier eating and enhanced physical activity. In
      2011, indices of obesity and physical fitness of 2474 younger (7.58 (sd 0.57)
      years) and 2330 older (10.30 (sd 0.51) years) children attending 193 of the 235
      primary schools were compared with historical measurements. After adjusting for
      age, sex, ethnicity, socio-economic status (SES) and school cluster effects, the
      combined prevalence of obesity and overweight among younger and older children in
      2011 was lower by 31 and 15 %, respectively, than that among 'unEnergized'
      children in the 2004 to 2006 RCT. Similarly, BMI was lower by 3.0 % (95 % CI -
      5.8, - 1.3) and 2.4 % (95 % CI - 4.3, - 0.5). Physical fitness (time taken to
      complete a 550 m run) was significantly higher in the Energized children (13.7
      and 11.3 %, respectively) than in a group of similarly aged children from another
      region. These effects were observed for boys and girls, both indigenous Maori and
      non-Maori children, and across SES. The long-term regional commitment to the
      Energize programme in schools may potentially lead to a secular reduction in the
      prevalence of overweight and obesity and gains in physical fitness, which may
      reduce the risk of developing obesity and type 2 diabetes. 

PMID- 23867070
TI  - Amoxicillin-clavulanic acid resistance in fecal Enterobacteriaceae from patients
      with cystic fibrosis and healthy siblings.
AB  - BACKGROUND: The present study set out to detect and identify amoxicillin
      clavulanic acid (AMC)-resistant Enterobacteriaceae in fecal samples of two
      patients with cystic fibrosis (CF) and their respective siblings. METHODS: Fecal
      Enterobacteriaceae were enumerated onto EMB agar containing amoxicillin (AMX). A
      total of 173 CF isolates and 41 sibling isolates were grouped into seven Matrix
      Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF
      MS) clusters and identified through 16S rRNA and rpoB sequence analysis. RESULTS:
      The fecal microbiota of patients with CF revealed a higher prevalence of AMX
      resistant Enterobacteriaceae compared to that of their healthy siblings. Whereas
      all selected isolates of healthy siblings were assigned to Escherichia coli,
      isolates of patients with CF belonged to Klebsiella oxytoca (58.4%), E. coli
      (28.3%), Klebsiella variicola (7.5%) or Citrobacter sp. (5.8%). All tested CF
      isolates showed a high resistance rate to AMX, and a lower level of resistance to
      the combination with clavulanic acid. In contrast, all tested sibling isolates
      were susceptible for both AMX and AMC. CONCLUSION: The higher abundance of AMX
      resistance in the investigated patients with CF suggests that frequent AMC
      administration may be one of the major contributing factors in the proliferation
      of Enterobacteriaceae and the development of resistant strains in the
      gastrointestinal tract.

PMID- 23867071
TI  - Hemoglobin <= 12.9 g/dl predicts risk of antibiotic treatment in cystic fibrosis.

PMID- 23867072
TI  - The effect of finger joint hypomobility on precision grip force.
AB  - STUDY DESIGN: Repeated measures experiment. INTRODUCTION: Traumatic injuries and
      certain other diseases of the hand typically affect mobility of the finger
      joints. Decreased mobility may alter grip force control while one is grasping and
      lifting objects. However, the effect of finger joint hypomobility on grip force
      control has not yet been systematically investigated. PURPOSE OF THE STUDY: The
      aim of this study was to investigate the effects of limited finger joint
      mobility, without other associated symptoms like pain, or sensory/proprioceptive
      deficits, on precision grip force control. METHODS: Fifteen healthy subjects
      performed a pinching and lifting task of an object equipped with a force sensor
      and an accelerometer, via opposition of the thumb and index finger, in the
      following experimental conditions: unrestricted finger joint movement (UJM),
      restricted finger flexion (RFF), restricted finger extension (RFE), mock
      restricted flexion (MRF), mock restricted extension (MRE). The following pinch
      force variables were measured and analyzed: grip force at lift off, grip force
      peak, load force peak, latency, and static force. RESULTS: A significant increase
      in latency (F = 4.41, p < 0.01) was noted during RFE relative to UJM and MRF
      conditions. There were no statistically-significant differences between the
      conditions among the other variables of precision grip force control.
      CONCLUSIONS: Limited joint mobility of the thumb and index finger may cause
      temporal changes in precision grip force control, which can lead to reduced
      manual dexterity. Restoring range of motion might be an important priority to
      improve thumb-index pinch force control during manipulative tasks.

PMID- 23867073
TI  - The ethics of doing nothing. Suicide-bereavement and research: ethical and
      methodological considerations.
AB  - BACKGROUND: Valuable trauma-related research may be hindered when the risks of
      asking participants about traumatic events are not carefully weighed against the
      benefits of their participation in the research. METHOD: The overall aim of our
      population-based survey was to improve the professional care of suicide-bereaved
      parents by identifying aspects of care that would be amenable to change. The
      study population included 666 suicide-bereaved and 377 matched (2:1) non-bereaved
      parents. In this article we describe the parents' perceptions of their contacts
      with us as well as their participation in the survey. We also present our ethical
      protocol for epidemiological surveys in the aftermath of a traumatic loss.
      RESULTS: We were able to contact 1410 of the 1423 eligible parents; eight of
      these parents expressed resentment towards the contact. Several participants and
      non-participants described their psychological suffering and received help
      because of the contact. A total of 666 suicide-bereaved and 377 non-bereaved
      parents returned the questionnaire. Just two out of the 1043 answered that they
      might, in the long term, be negatively affected by participation in the study;
      one was bereaved, the other was not. A significant minority of the parents
      reported being temporarily negatively affected at the end of their participation,
      most of them referring to feelings of sadness and painful memories. In parallel,
      positive experiences were widely expressed and most parents found the study
      valuable. CONCLUSIONS: Our findings suggest, given that the study design is
      ethically sound, that suicide-bereaved parents should be included in research
      since the benefits clearly outweigh the risks.

PMID- 23867074
TI  - Evaluation of a real-time PCR assay based on the single-copy SAG1 gene for the
      detection of Toxoplasma gondii.
AB  - Real-time PCR-based detection of Toxoplasma gondii is very sensitive and
      convenient for diagnosing toxoplasmosis. However, the performance of the PCR
      assays could be influenced by the target gene chosen. Here we evaluate a real
      time PCR assay using double-stranded DNA dyes (SYBR((r)) Green I assay) with a
      new set of primers targeting the SAG1 gene for the fast and specific detection of
      T. gondii. The assay showed higher sensitivity than conventional PCR protocols
      using T. gondii DNA as template. The detection limit of the developed real-time
      PCR assay was in the order of 1 tachyzoite. The assay was also assessed by
      experimentally infected mice and showed positive results for blood (25%), spleen
      (50%) and lung (50%) as early as 1 dpi. The specificity of the assay was
      confirmed by using DNA from Neospora caninum, Escherichia coli, Babesia bovis,
      Trypanosoma brucei, Cryptosporidium parvum, and Toxocara canis. Assay
      applicability was successfully tested in blood samples collected from slaughtered
      pigs. These results indicate that, based on SYBR((r)) green I, the quantitative
      SAG1 assay may also be useful in the study of the pathogenicity,
      immunoprophylaxis, and treatment of T. gondii.

PMID- 23867075
TI  - 'Sealing off the CNS': cellular and molecular regulation of blood-brain
      barriergenesis.
AB  - From their initial ingression into the neural tube to the established, adult
      vascular plexus, blood vessels within the CNS are truly unique. Covered by a
      virtually continuous layer of perivascular cells and astrocytic endfeet and
      connected by specialized cell-cell junctional contacts, mature CNS blood vessels
      simultaneously provide nutritive blood flow and protect the neural milieu from
      potentially disruptive or harmful molecules and cells flowing through the vessel
      lumen. In this review we will discuss how the CNS vasculature acquires blood
      brain barrier (BBB) properties with a specific focus on recent work identifying
      the cell types and molecular pathways that orchestrate barriergenesis. 

PMID- 23867076
TI  - Significantly improved performance of a multitarget assay over a commercial
      SCCmec-based assay for methicillin-resistant Staphylococcus aureus screening:
      applicability for clinical laboratories.
AB  - Detection of the SCCmec gene is a common strategy for methicillin-resistant
      Staphylococcus aureus (MRSA) screening assays. However, if SCCmec is used alone,
      it may not be specific for detecting MRSA. Herein, we describe an in-house MSRA
      PCR-based screening assay involving detection of three targets (nuc, coa, and
      mecA). The assay is suitable for a wide range of real-time PCR platforms used in
      clinical microbiological laboratories. Performance characteristics of the in
      house assay were significantly improved compared with the commercial assay,
      leading to an increase of positive predictive value by 40%. Compared with the
      bacterial culture, the sensitivity, specificity, and positive and negative
      predictive values of the in-house PCR assay were 100% (95% CI >83.2%), 99.2% (95%
      CI = 98.2% to 99.8%), 80% (95% CI = 59.3% to 93.2%), and 100% (95% CI >99.2%),
      respectively. 

PMID- 23867077
TI  - When less is more: a functional magnetic resonance imaging study of verbal
      working memory in remitted depressed patients.
AB  - BACKGROUND: Patients with depression show abnormalities in the neural circuitry
      supporting working memory. However, it is unclear if these abnormalities are
      present in unmedicated remitted depressed patients. To address this question, the
      current study employed functional magnetic resonance imaging (fMRI), in
      combination with a simple verbal n-back task, in a cohort of unmedicated remitted
      depressed patients. METHOD: We studied 15 healthy control subjects (HC) and 15
      unmedicated remitted depressed patients (rMDD). Participants performed a verbal
      working memory task of varying cognitive load (n-back) while undergoing fMRI. We
      used multiple regression analyses to assess overall capacity (1-, 2-, 3-back
      versus 0-back) as well as quadratic modulation of cognitive demand. RESULTS:
      Performance accuracy and response latency did not differ between groups, and
      overall capacity was similar. However, rMDD showed a positive quadratic load
      response in the bilateral hippocampus; the converse was true for HC. CONCLUSIONS:
      Our data suggest that remitted depression was associated with a perturbed pattern
      of activation in the bilateral hippocampus during a verbal working memory task.
      We propose that a reduced ability to dampen task-irrelevant activity may reflect
      a neurobiological risk factor for recurrent depression.

PMID- 23867078
TI  - Pharmacokinetic comparisons of two different combinations of Shaoyao-Gancao
      Decoction in rats: competing mechanisms between paeoniflorin and glycyrrhetinic
      acid.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Shaoyao-Gancao Decoction (SGD), a well-known
      traditional Chinese medicine prescription, is a combination of Radix Paeoniae
      Alba (Paeonia lactiflora Pall, root) and Glycyrrhizae uralensis (Glycyrrhiza
      uralensis Fisch., root and rhizome, honeyed) for spasmolysis and emergency pain
      relief. Paeoniflorin (PF) and glycyrrhetinic acid (GA) are two typical active
      components of SGD for pain relief. AIM OF THE STUDY: To study comparative
      pharmacokinetics of ten bioactive compounds in SGDs with two different
      combinations of RP and GU, and therefore to investigate the herb-herb interaction
      mechanisms of Shaoyao-Gancao Decoction for better spasmolysis and emergency pain
      relief in rats. MATERIALS AND METHODS: Herbal IR macro-fingerprinting was
      implemented to provide the full chemical fingerprints of RP, GU and SGD
      decoctions and to investigate the variation rule of the full chemical profile of
      SGDs with various combinations of RP and GU. A specifically developed HPLC-MS/MS
      assay coupled with protein precipitation method was employed to determine the
      plasma concentrations of the ten analytes. Male Wistar rats were orally
      administered with SGD1 (RP:GU, 1:1 (w/w)) and SGD2 ((RP:GU, 4:1 (w/w)) equivalent
      to 9.5 g/kg body weight of GU. RESULTS: Full chemical fingerprints of RP, GU and
      SGDs with various combinations of RP and GU were provided in the form of IR macro
      fingerprints. Except for liquiritin, there were statistically significant
      differences (p<0.05 or p<0.01) of these analytes between SGD1 and SGD2 in in vivo
      pharmacokinetic study. Compared with the results when oral administrated with
      SGD1, six glycosides (PF, albiflorin, oxypaeoniflorin, isoliquiritin, ononin, and
      glycyrrhizin) exhibited higher systematic exposure levels (AUC0-t) and slower
      elimination rates (CL) whereas two glycones (GA and isoliquiritigenin) were the
      reverse when administrated with SGD2. CONCLUSIONS: Increasing the amount of RP
      attenuated the inhibitory effect of GA via competing being consumed by intestinal
      bacteria (or beta-glucosidase) to reduce the conversion amount of glycyrrhizin to
      GA and subsequently to afford significantly higher bioavailability and longer
      efficacy of PF, glycyrrhizin, albiflorin, oxypaeoniflorin, isoliquiritin, and
      ononin, leading to better spasmolysis and emergency pain relief.

PMID- 23867079
TI  - A novel approach to improve the efficacy of tumour ablation during cryosurgery.
AB  - Freezing tumours and ablating it using cryosurgery is becoming a popular surgical
      procedure for treatment of carcinomas. In order to improve the efficiency of the
      cryosurgical procedure different approaches have been implemented till now, e.g.,
      injecting high thermal conductivity fluid inside the tumour, low latent heat
      fluids inside the tumour prior to cryosurgery etc. These techniques improve the
      cryosurgical process to some extent but lack in minimising the damage to the
      surrounding healthy tissues. In this study, a novel concept is proposed which
      advocates the use of solutions with specific thermophysical properties around the
      interface of tumour. Numerical modelling has been done to determine the location
      of the ice fronts in the presence of this solution around the boundary of the
      tumour. It is noticed that in the presence of solution layer, owing to its
      distinct thermophysical properties like low thermal conductivity, not only the
      cellular destruction is enhanced but also the damage to the surrounding healthy
      tissue is minimised. Further, results indicate that this strategy leads to a
      faster ablation rate reducing the surgical time immensely. Also, an optimal
      offset, the minimum distance between the tip of cryoprobe and the boundary of the
      tumour, is identified for a given tumour radius with a given active length which
      gives maximum tumour necrosis in less time. This optimal offset which has been
      identified for each case will help the surgeons in proper planning of cryosurgery
      and improving the effectiveness of this technique greatly, making it a better
      treatment modality than its counterparts in many ways. It is also observed that
      for a 2 mm increase in activelength of the cryoprobe, the decrease in optimal
      offset is approximately 1 mm, i.e. optimal offset decreases linearly with an
      increase in the activelength for a given radius of the tumour. Also, for tumour
      with different radii, ranging between 10 mm to 15 mm, with same active length,
      the time taken for complete ablation by the larger tumour is nearly 2.7 times the
      time taken by the smaller one for every 2.5 mm increase in the tumour radius.

PMID- 23867080
TI  - Assessment of executive function in adolescence: a comparison of traditional and
      virtual reality tools.
AB  - Paper-pencil type tests are traditionally used in the assessment of executive
      functions (EF); however, concerns have been raised as to whether these represent
      actual functioning in everyday life. Virtual reality (VR) environments offer a
      novel alternative for the assessment of cognitive function and therefore have the
      potential to enhance the evaluation of EF by presenting individuals with stimuli
      that come closer to reproducing everyday situations. The aims of this study were
      to (1) establish which traditional paper-pencil EF tests from the Delis-Kaplan
      Executive Function System (D-KEFS) are associated with performance on a VR-Stroop
      task and (2) compare D-KEFS tests and the VR-Stroop task in their ability to
      predict everyday EF and behavior, as measured by the Behavioral Rating Inventory
      of Executive Function (BRIEF) and the Child Behavior Checklist (CBCL). Thirty
      eight typically developing adolescents aged between 13 and 17 years completed the
      ClinicaVR: Classroom-Stroop, and five D-KEFS subtests (Trail Making, Tower,
      Twenty Questions, Verbal Fluency and Color-Word Interference). Their parents
      completed the BRIEF and CBCL questionnaires. The results indicate that
      performance on the VR-Stroop task correlates with both traditional forms of EF
      assessment (D-KEFS, BRIEF). In particular, performance on the VR-Stroop task was
      closely associated with performance on a paper-pencil inhibition task.
      Furthermore, VR-Stroop performance more accurately reflected everyday behavioral
      EF than paper-pencil tasks. VR appears to offer an ecological perspective on
      everyday functioning and could be seen as complementary to traditional tests in
      the assessment of complex cognitive abilities.

PMID- 23867082
TI  - A review of Brucella seroprevalence among humans and animals in Bangladesh with
      special emphasis on epidemiology, risk factors and control opportunities.
AB  - Brucellosis is a neglected bacterial zoonotic disease in many countries affecting
      both humans and animals. The aim of this paper is to review published reports of
      the seroprevalence of brucellosis in humans and animals (cattle, buffalo, sheep,
      goats and dogs) in Bangladesh. The prevalence studies are based primarily on the
      following serological tests: rose bengal plate agglutination test (RBT), plate
      agglutination test (PAT), tube agglutination test (TAT), mercaptoethanol
      agglutination test (MET), standard tube agglutination test (STAT), slow
      agglutination test (SAT), milk ring test (MRT), indirect enzyme-linked
      immunosorbant assay (I-ELISA), competitive ELISA (C-ELISA) and fluorescent
      polarization assay (FPA). Seroprevalences of brucellosis were found to be
      affected by the sensitivity and specificity of serological tests employed.
      Brucellosis prevalence varied based on occupations of people (2.5-18.6%) and
      species of animals (3.7% in cattle, 4.0% in buffalo, 3.6% in goats and 7.3% in
      sheep). The prevalence of brucellosis in humans was reported in livestock farmers
      (2.6-21.6%), milkers (18.6%), butchers (2.5%) and veterinarians (5.3-11.1%) who
      have direct contact with animal and its products or who consume raw milk.
      According to published reports brucellosis does affect people and livestock of
      Bangladesh. There is an immediate need for a concerted effort to control and
      eradicate brucellosis from domesticated animals in Bangladesh. 

PMID- 23867081
TI  - A coaxial optrode as multifunction write-read probe for optogenetic studies in
      non-human primates.
AB  - BACKGROUND: Advances in optogenetics have led to first reports of expression of
      light-gated ion-channels in non-human primates (NHPs). However, a major obstacle
      preventing effective application of optogenetics in NHPs and translation to
      optogenetic therapeutics is the absence of compatible multifunction
      optoelectronic probes for (1) precision light delivery, (2) low-interference
      electrophysiology, (3) protein fluorescence detection, and (4) repeated insertion
      with minimal brain trauma. NEW METHOD: Here we describe a novel brain probe
      device, a "coaxial optrode", designed to minimize brain tissue damage while
      microfabricated to perform simultaneous electrophysiology, light delivery and
      fluorescence measurements in the NHP brain. The device consists of a tapered,
      gold-coated optical fiber inserted in a polyamide tube. A portion of the gold
      coating is exposed at the fiber tip to allow electrophysiological recordings in
      addition to light delivery/collection at the tip. RESULTS: Coaxial optrode
      performance was demonstrated by experiments in rodents and NHPs, and
      characterized by computational models. The device mapped opsin expression in the
      brain and achieved precisely targeted optical stimulation and electrophysiology
      with minimal cortical damage. COMPARISON WITH EXISTING METHODS: Overall, combined
      electrical, optical and mechanical features of the coaxial optrode allowed a
      performance for NHP studies which was not possible with previously existing
      devices. CONCLUSIONS: Coaxial optrode is currently being used in two NHP
      laboratories as a major tool to study brain function by inducing light modulated
      neural activity and behavior. By virtue of its design, the coaxial optrode can be
      extended for use as a chronic implant and multisite neural stimulation/recording.

PMID- 23867083
TI  - Multiple routes of porcine circovirus type 2 transmission to piglets in the
      presence of maternal immunity.
AB  - Porcine circovirus 2 (PCV2), the cause of porcine circovirus-associated disease
      (PCVAD), is widespread in swine farms throughout the United States with vaccine
      controlling disease, but not eliminating infection. We examined the PCV2
      virological and immunological status of sows, pre-suckling piglets, and the
      farrowing environment of sow farms to determine PCV2 exposure risks, transmission
      dynamics, and immunological impacts at the time of farrowing. PCV2 was widely
      distributed in animals and the farrowing environment of 6 midwestern US sow farms
      irrespective of sow vaccination status. High levels of PCV2 capsid-specific
      antibodies were observed in sow serum and colostrum and had no apparent effect on
      PCV2 transmission to and infection in piglets. In 281 pre-suckling piglets from
      59 sows, PCV2 DNA was detected in 63% of serum samples and on 93% of axillary
      skin swabs. PCV2 was present in one or more samples from 58 of 59 sows and in the
      farrowing environment. Isolated infectious virus samples from sows, presuckling
      piglets, and the environment were shown by sequencing to be genetically similar
      from all farms. In conclusion, piglets are readily infected with PCV2 in utero
      and are under constant challenge by PCV2 through contact with infected sows and a
      contaminated farrowing environment. However, maternal immunity did not affect
      PCV2 transmission to piglets or the viral load in sows. These findings illustrate
      the importance of maternal infection, despite robust anti-PCV2 immunity, in early
      infection of newborn piglets, and the need to develop appropriate infection
      models for elucidation of mechanisms of protective immunity. 

PMID- 23867084
TI  - Antimicrobial resistance selection in avian pathogenic E. coli during treatment.
AB  - An experiment was performed to compare the microbiological efficacy of four
      treatments (oxytetracycline, trimethoprim-sulphonamide, amoxicillin (AMX) or
      enrofloxacin (ENR)) to control experimental colibacillosis induced by an avian
      pathogenic Escherichia coli (APEC) with reduced susceptibility to
      fluoroquinolones. The protocol was also developed in order to study resistance
      gene transfer. Broilers were first orally inoculated with multiresistant E. coli
      bearing plasmid genes conferring resistance to fluoroquinolones (qnr),
      cephalosporins (blaCTX-M or blaFOX), tetracycline or trimethoprim-sulphonamide.
      They were then inoculated in their air sacs with the APEC and treated as soon as
      symptoms appeared. Internal organs from dead or sacrificed birds were cultivated
      on non-supplemented or supplemented media. The inoculated O78 APEC was recovered
      significantly less frequently in ENR treated group (26%) compared to untreated
      group (47%). This was not true for other treated groups. Isolates obtained on non
      supplemented media had the same susceptibility profile as the inoculated APEC.
      However, one isolate from the AMX-treated group obtained on AMX-supplemented
      media was resistant to AMX only, and one isolate from the same group obtained on
      ENR-supplemented media, showed a resistance profile suggesting acquisition of one
      of the multiresistance plasmids present in the intestinal microbiota. Molecular
      analysis performed on this multiresistant isolate confirmed the presence of a
      conjugative plasmid with qnr and blaCTX-M resistance genes. Thus, the experiment
      illustrated the emergence of resistant isolates in internal organs, probably via
      acquisition of a plasmid from the intestinal microbiota. 

PMID- 23867085
TI  - Developing an assessment of fire-setting to guide treatment in secure settings:
      the St Andrew's Fire and Arson Risk Instrument (SAFARI).
AB  - BACKGROUND: Arson and fire-setting are highly prevalent among patients in secure
      psychiatric settings but there is an absence of valid and reliable assessment
      instruments and no evidence of a significant approach to intervention. AIMS: To
      develop a semi-structured interview assessment specifically for fire-setting to
      augment structured assessments of risk and need. METHOD: The extant literature
      was used to frame interview questions relating to the antecedents, behaviour and
      consequences necessary to formulate a functional analysis. Questions also covered
      readiness to change, fire-setting self-efficacy, the probability of future fire
      setting, barriers to change, and understanding of fire-setting behaviour. The
      assessment concludes with indications for assessment and a treatment action plan.
      The inventory was piloted with a sample of women in secure care and was assessed
      for comprehensibility, reliability and validity. RESULTS: Staff rated the St
      Andrews Fire and Risk Instrument (SAFARI) as acceptable to patients and easy to
      administer. SAFARI was found to be comprehensible by over 95% of the general
      population, to have good acceptance, high internal reliability, substantial test
      retest reliability and validity. CONCLUSIONS: SAFARI helps to provide a clear
      explanation of fire-setting in terms of the complex interplay of antecedents and
      consequences and facilitates the design of an individually tailored treatment
      programme in sympathy with a cognitive-behavioural approach. Further studies are
      needed to verify the reliability and validity of SAFARI with male populations and
      across settings.

PMID- 23867086
TI  - Simultaneous analysis of oxybutynin and its active metabolite N-desethyl
      oxybutynin in human plasma by stable isotope dilution LC-MS/MS to support a
      bioequivalence study.
AB  - An isotope dilution high performance liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method has been developed for the simultaneous
      determination of oxybutynin and its pharmacologically active metabolite N
      desethyl oxybutynin in human plasma. Extraction of oxybutynin, its metabolite and
      their deuterated analogs as internal standards (ISs) from 300 MUL human plasma
      was carried out by liquid-liquid extraction with methyl tert-butyl ether-ethyl
      acetate solvent mixture. Chromatographic separation of analytes was performed on
      Cosmosil C18 (150 mm * 4.6 mm, 5 MUm) column under isocratic conditions with
      acetonitrile-1.0mM ammonium acetate (90:10, v/v) as the mobile phase. Six
      endogenous plasma phospholipids (496.3/184.0, 524.3/184.0, 758.5/184.0,
      786.5/184.0, 806.5/184.0 and 810.5/184.0) were monitored to determine the
      extraction efficiency under different extraction conditions. The precursor
      >product ion transition for both the analytes and ISs were monitored on a triple
      quadrupole mass spectrometer, operating in the multiple reaction monitoring and
      positive ionization mode. The method was validated over a concentration range of
      0.050-10.0 ng/mL for oxybutynin and 0.500-100 ng/mL for N-desethyl oxybutynin.
      The mean extraction recovery for analytes (80.4%) and ISs (76.9%) was consistent
      across five QC levels. Bench top, wet and dry extract, freeze-thaw and long term
      stability was evaluated for both the analytes. The method was applied to support
      a bioequivalence study of 5mg tablet formulation in 74 healthy Indian subjects.
      Assay reproducibility was demonstrated by reanalysis of 344 incurred samples.

PMID- 23867087
TI  - Application of isotope-based carboxy group derivatization in LC-MS/MS analysis of
      tissue free-fatty acids for thyroid carcinoma.
AB  - Free fatty acids (FFAs) analysis of human tissue is challenging due to the low
      abundance of tissue lipids and interference from the complex matrix. Based on our
      previously reported on 2,4-dimethoxy-6-piperazin-1-yl pyrimidine (DMPP)
      derivatization toward carboxy group, we have further applied DMPP derivatization
      method in the assay of tissue FFAs in patients with thyroid carcinoma after
      method optimization including sample pretreatment, and derivatization condition.
      d6-DMPP labeled mixture of FFAs standard was used as the internal standard (IS).
      The d0-DMPP labeled samples (spiked with IS) were subsequently used for lipids
      profiling by selective reaction monitoring (SRM) detection. The DMPP
      derivatization combined with SRM not only allowed trace analysis of FFAs in
      complex matrix due to the extremely high sensitivity, but also minimized the
      errors in quantitation because of the very similar property between d0-DMPP
      derivatized samples and d6-DMPP derivatized IS. Eighteen kinds of FFAs were
      detected successfully with the increased level in carcinoma tissue compared with
      the normal tissue, which may be the results of abnormality in the metabolism of
      fatty acid synthases and lipids. Application of the DMPP based FFAs
      derivatization is expected to provide a promising tool for the investigation of
      lipids in vivo, especially for the research of lipid metabolism. 

PMID- 23867088
TI  - A rapid method for the determination of artemisinin and its biosynthetic
      precursors in Artemisia annua L. crude extracts.
AB  - A rapid high-pressure liquid chromatography (HPLC) tandem mass spectrometry (TQD)
      method for the determination of artemisinin, 9-epi-artemisinin, artemisitene,
      dihydroartemisinic acid, artemisinic acid and arteannuin B in Artemisia annua
      extracts is described. Detection and quantification of 9-epi-artemisinin in crude
      extracts are reported for the first time. In this method all six metabolites are
      resolved and eluted within 6 min with minimal sample preparation. A recovery of
      between 96.25% and 103.59% was obtained for all metabolites analysed and the
      standard curves were linear (r(2)>0.99) over the concentration range of 0.15-10
      MUg mL(-1) for artemisinin, 9-epi-artemisinin, artemisitene and arteannuin B, and
      the range of 3.75-120 MUg mL(-1) for dihydroartemisinic acid and artemisinic
      acid. All validation indices were satisfactory, showing the method to be robust,
      quick, sensitive and adequate for a range of applications including high
      throughput (HTP) analysis.

PMID- 23867089
TI  - Mass spectrometric characterization of glucuronides formed by a new concept,
      combining Cunninghamella elegans with TEMPO.
AB  - A new concept for the production of drug glucuronides is presented and the
      products formed were characterized using ultra high performance liquid
      chromatography-high resolution mass spectrometry (UPLC-HRMS). Glucuronic acid
      conjugates are important phase II metabolites of a wide range of drugs. There is
      a lack of commercially available glucuronides and classic synthetic methods are
      tedious and expensive. Thus, new methods of glucuronide synthesis are needed.
      Selective androgen receptor modulators (SARMs) of the aryl propionamide class
      were used as model compounds and were incubated with the fungus Cunninghamella
      elegans which was previously known to conjugate drugs with glucose. The resulting
      glucoside metabolites were then oxidized with tetramethylpiperidinyl-1-oxy
      (TEMPO). UPLC-HRMS analysis showed that the peaks corresponding to the glucosides
      had disappeared after the reaction and were replaced by peaks with m/z consistent
      with the corresponding glucuronic acid conjugates. The MS/MS spectra of the
      reaction products were investigated and the observed fragment ion pattern
      corroborated the suggested structural change. A comparison in terms of retention
      times and product ion spectra between the glucuronides formed by the new method
      and those produced by liver microsomes indicated that the conjugates from the two
      different sources were identical, thus demonstrating the human relevance of the
      presented technique. Furthermore, the glucuronides formed by the presented method
      were readily hydrolyzed by beta-glucuronidase which further gave evidence as to
      the fact that they were of beta configuration. The investigated method was easy
      to perform, required a low input of work and had a low cost. 

PMID- 23867090
TI  - Validation of the English version of the UNESP-Botucatu multidimensional
      composite pain scale for assessing postoperative pain in cats.
AB  - BACKGROUND: A scale validated in one language is not automatically valid in
      another language or culture. The purpose of this study was to validate the
      English version of the UNESP-Botucatu multidimensional composite pain scale
      (MCPS) to assess postoperative pain in cats. The English version was developed
      using translation, back-translation, and review by individuals with expertise in
      feline pain management. In sequence, validity and reliability tests were
      performed. RESULTS: Of the three domains identified by factor analysis, the
      internal consistency was excellent for 'pain expression' and 'psychomotor change'
      (0.86 and 0.87) but not for 'physiological variables' (0.28). Relevant changes in
      pain scores at clinically distinct time points (e.g., post-surgery, post
      analgesic therapy), confirmed the construct validity and responsiveness (Wilcoxon
      test, p < 0.001). Favorable correlation with the IVAS scores (p < 0.001) and
      moderate to very good agreement between blinded observers and 'gold standard'
      evaluations, supported criterion validity. The cut-off point for rescue analgesia
      was > 7 (range 0-30 points) with 96.5% sensitivity and 99.5% specificity.
      CONCLUSIONS: The English version of the UNESP-Botucatu-MCPS is a valid, reliable
      and responsive instrument for assessing acute pain in cats undergoing
      ovariohysterectomy, when used by anesthesiologists or anesthesia technicians. The
      cut-off point for rescue analgesia provides an additional tool for guiding
      analgesic therapy.

PMID- 23867091
TI  - Effects of combined liver and udder biopsying on the acute phase response of
      dairy cows with experimentally induced E. coli mastitis.
AB  - A minimally invasive biopsy technique was evaluated for udder tissue collection
      in dairy cows with Escherichia coli mastitis. Meanwhile, the effect of taking
      repeated liver and udder biopsies on the systemic and local acute phase response
      (APR) of the dairy cows was investigated during the disease. The cows were
      divided into a biopsy group (B) (n = 16) and a no-biopsy group (NB) (n = 16) and
      were sampled in the acute disease stage and in the recovery stage. The cows' pre
      disease period served as a control period for establishing baseline values for
      the investigated parameters. A total of 32 Holstein-Friesian cows were inoculated
      with 20 to 40 colony-forming units (cfu) of E. coli in one front quarter at 0
      hour. Liver biopsies were collected at -144, 12, 24 and 192 h, and udder biopsies
      were collected at 24 and 192 h post E. coli inoculation (PI) using a minimally
      invasive biopsy technique. Effects of combined biopsying were investigated by
      recording production traits, clinical response, and measuring inflammatory milk
      and blood parameters: E. coli, somatic cell count, milk amyloid A (MAA) levels,
      white blood cell count, polymorphonuclear neutrophilic leukocyte numbers and
      serum amyloid A levels at several time points. E. coli inoculation changed all
      production parameters and the clinical and inflammatory response in all cows
      except one that was not infected. Combined biopsying had no constant or transient
      effect on the daily feed intake, the clinical responsiveness or the blood
      parameters, but affected the daily milk yield and some milk parameters
      transiently, that is, the presence of blood in milk, increased E. coli counts and
      MAA levels during the acute disease stage. Combined biopsying had no effect on
      the parameters in the recovery stage apart from the presence of blood in the
      milk. In conclusion, although, a minimally invasive biopsy technique was used,
      tissue damages could not be avoided when biopsying and they transiently affected
      the inflammatory parameters in the mammary gland. Nevertheless, we believe
      combined biopsying of liver and udder is as an acceptable approach to study the
      systemic and local APR in dairy cows during E. coli mastitis, if the timing of
      biopsying and other types of sampling is planned accordingly.

PMID- 23867092
TI  - China action of "Cleanup Plan for Polychlorinated Biphenyls Burial Sites":
      emissions during excavation and thermal desorption of a capacitor-burial site.
AB  - Scarce data are available so far on emissions in a given scenario for excavation
      and thermal desorption, a common practice, of soils contaminated with
      polychlorinated biphenyls (PCBs). As part of China action of "Cleanup Plan for
      PCBs Burial Sites", this study roughly estimated PCBs emissions in the scenario
      for a capacitor-burial site. The concentrations of total PCBs (22 congeners) in
      soils were in the range of 2.1-16,000MUg/g with a mean of 2300MUg/g, among the
      same order of magnitude as the highest values obtained in various PCBs
      contaminated sites. Only six congeners belonging to Di-, Tri-, and Tetra-CBs were
      observed above limits of detection in air samples in the scenario, partially
      which can be estimated by the USEPA air emission model. Comparing concentrations
      and composition profiles of PCBs in the soil and air samples further indicated a
      leaked source of commercial PCBs formulations of trichlorobiphenyl (China PCB no.
      1). The measures taken if any to mitigate the volatilization and movement of PCBs
      and to minimize worker exposure were discussed for improvements of the excavation
      practice. 

PMID- 23867093
TI  - Bioluminescence enhancement through an added washing protocol enabling a greater
      sensitivity to carbofuran toxicity.
AB  - The effects of carbofuran toxicity on a genetically modified bacterial strain E.
      coli DPD2794 were enhanced using a new bioluminescent protocol which consisted of
      three consecutive steps: incubation, washing and luminescence reading.
      Specifically, in the first step, several concentrations of carbofuran aqueous
      solutions were incubated with different bacterial suspensions at recorded optical
      densities for different lengths of time. Thereafter, the resulting
      bacterial/toxicant mixtures were centrifuged and the aged cellular supernatant
      replaced with fresh medium. In the final step, the carbofuran- induced
      bioluminescence to the exposed E. coli DPD2794 bacteria was shown to provide a
      faster and higher intensity when recorded at a higher temperature at30 degrees C
      which is not usually used in the literature. It was found that the incubation
      time and the replacement of aged cellular medium were essential factors to
      distinguish different concentrations of carbofuran in the bioluminescent assays.
      From our results, the optimum incubation time for a "light ON" bioluminescence
      detection of the effect of carbofuran was 6h. Thanks to the replacement of the
      aged cellular medium, a group of additional peaks starting around 30min were
      observed and we used the corresponding areas under the curve (AUC) at different
      contents of carbofuran to produce the calibration curve. Based on the new
      protocol, a carbofuran concentration of 0.5pg/mL can be easily determined in a
      microtiter plate bioluminescent assay, while a non-wash protocol provides an
      unexplainable order of curve evolutionswhich does not allow the user to determine
      the concentration. 

PMID- 23867094
TI  - Re: Burn care centres are lacking at major trauma centres in the United Kingdom.

PMID- 23867095
TI  - Isolation of a high malic and low acetic acid-producing sake yeast Saccharomyces
      cerevisiae strain screened from respiratory inhibitor 2,4-dinitrophenol (DNP)
      resistant strains.
AB  - We isolated 2,4-dinitrophenol (DNP)-resistant sake yeast strains by UV
      mutagenesis. Among the DNP-resistant mutants, we focused on strains exhibiting
      high malic acid and low acetic acid production. The improved organic acid
      composition is unlikely to be under the control of enzyme activities related to
      malic and acetic acid synthesis pathways. Instead, low mitochondrial activity was
      observed in DNP-resistant mutants, indicating that the excess pyruvic acid
      generated during glycolysis is not metabolized in the mitochondria but converted
      to malic acid in the cytosol. In addition, the NADH/NAD(+) ratio of the DNP
      resistant strains was higher than that of the parental strain K901. These results
      suggest that the increased NADH/NAD(+) ratio together with the low mitochondrial
      activity alter the organic acid composition because malic acid synthesis requires
      NADH, while acetic acid uses NAD(+). 

PMID- 23867096
TI  - Highly sensitive and selective analysis of widely targeted metabolomics using gas
      chromatography/triple-quadrupole mass spectrometry.
AB  - In metabolomics studies, gas chromatography coupled with time-of-flight or
      quadrupole mass spectrometry has frequently been used for the non-targeted
      analysis of hydrophilic metabolites. However, because the analytical platform
      employs the deconvolution method to extract single-metabolite information from co
      eluted peaks and background noise, the extracted peak is artificial product
      depending on the mathematical parameters and is not completely compatible with
      the pure component obtained by analyzing a standard compound. Moreover, it has
      insufficient ability for quantitative metabolomics. Therefore, highly sensitive
      and selective methods capable of pure peak extraction without any complicated
      mathematical techniques are needed. For this purpose, we have developed a novel
      analytical method using gas chromatography coupled with triple-quadrupole mass
      spectrometry (GC-QqQ/MS). We developed a selected reaction monitoring (SRM)
      method to analyze the trimethylsilyl derivatives of 110 metabolites, using
      electron ionization. This methodology enables us to utilize two complementary
      techniques-non-targeted and widely targeted metabolomics in the same sample
      preparation protocol, which would facilitate the formulation or verification of
      novel hypotheses in biological sciences. The GC-QqQ/MS analysis can accurately
      identify a metabolite using multichannel SRM transitions and intensity ratios in
      the analysis of living organisms. In addition, our methodology offers a wide
      dynamic range, high sensitivity, and highly reproducible metabolite profiles,
      which will contribute to the biomarker discoveries and quality evaluations in
      biology, medicine, and food sciences.

PMID- 23867097
TI  - Effects of water on reactions for waste treatment, organic synthesis, and bio
      refinery in sub- and supercritical water.
AB  - Current research analyzing the effects of water in the field of homogeneous and
      heterogeneous reactions of organics in sub- and supercritical water are reviewed
      in this article. Since the physical properties of water (e.g., density, ion
      product and dielectric constants) can affect the reaction rates and mechanisms of
      various reactions, understanding the effects that water can have is important in
      controlling reactions. For homogeneous reactions, the effects of water on
      oxidation, hydrolysis, aldol condensation, Beckman rearrangement and biomass
      refining were introduced including recent experimental results up to 100 MPa
      using special pressure-resistance equipment. For heterogeneous reactions, the
      effects of ion product on acid/base-catalyzed reactions, such as hydrothermal
      conversion of biomass-related compounds, organic synthesis in the context of bio
      refinery, and hydration of olefins were described and how the reaction paths are
      controlled by the concentration of water and hydrogen ions was summarized.

PMID- 23867098
TI  - Energy conversion of biomass with supercritical and subcritical water using large
      scale plants.
AB  - Exploiting unused or waste biomass as an alternative fuel is currently receiving
      much attention because of the potential reductions in CO2 emissions and the lower
      cost in comparison to expensive fossil fuels. If we are to use biomass
      domestically or industrially, we must be able to convert biomass to high-quality
      and easy-to-use liquid, gas, or solid fuels that have high-calorific values, low
      moisture and ash contents, uniform composition, and suitable for stored over long
      periods. In biomass treatment, hot and high-pressure water including
      supercritical and subcritical water is an excellent solvent, as it is clean and
      safe and its action on biomass can be optimized by varying the temperature and
      pressure. In this article, the conversion of waste biomass to fuel using hot and
      high-pressure water is reviewed, and the following examples are presented: the
      production of large amounts of hydrogen from waste biomass, the production of
      cheap bioethanol from non-food raw materials, and the production of composite
      powder fuel from refractory waste biomass in the rubble from the Great East Japan
      Earthquake. Several promising techniques for the conversion of biomass have been
      demonstrated in large-scale plants and commercial deployment is expected in the
      near future. 

PMID- 23867099
TI  - Gram-scale production of a basidiomycetous laccase in Aspergillus niger.
AB  - We report on the expression in Aspergillus niger of a laccase gene we used to
      produce variants in Saccharomyces cerevisiae. Grams of recombinant enzyme can be
      easily obtained. This highlights the potential of combining this generic laccase
      sequence to the yeast and fungal expression systems for large-scale productions
      of variants. 

PMID- 23867100
TI  - Accessibility of fitness centres for people with disabilities in a region in
      North East Scotland.

PMID- 23867101
TI  - Arts on prescription: a qualitative outcomes study.
AB  - OBJECTIVES: In recent years, participatory community-based arts activities have
      become a recognized and regarded method for promoting mental health. In the UK,
      Arts on Prescription services have emerged as a prominent form of such social
      prescribing. This follow-up study reports on the findings from interviews
      conducted with participants in an Arts on Prescription programme two years after
      previous interviews to assess levels of 'distance travelled'. STUDY DESIGN: This
      follow-up study used a qualitative interview method amongst participants of an
      Arts on Prescription programme of work. METHODS: Ten qualitative one-to-one
      interviews were conducted in community-based arts venues. Each participant was
      currently using or had used mental health services, and had been interviewed two
      years earlier. Interviews were digitally recorded, transcribed and analysed.
      RESULTS: For each of the 10 participants, a lengthy attendance of Arts on
      Prescription had acted as a catalyst for positive change. Participants reported
      increased self-confidence, improved social and communication skills, and
      increased motivation and aspiration. An analysis of each of the claims made by
      participants enabled them to be grouped according to emerging themes: education:
      practical and aspirational achievements; broadened horizons: accessing new
      worlds; assuming and sustaining new identities; and social and relational
      perceptions. Both hard and soft outcomes were identifiable, but most were soft
      outcomes. CONCLUSIONS: Follow-up data indicating progress varied between
      respondents. Whilst hard outcomes could be identified in individual cases, the
      unifying factors across the sample were found predominately in the realm of soft
      outcomes. These soft outcomes, such as raised confidence and self-esteem,
      facilitated the hard outcomes such as educational achievement and voluntary work.

PMID- 23867102
TI  - Molecular Oncology. Editorial.

PMID- 23867103
TI  - New members of the editorial board--personal profiles.

PMID- 23867104
TI  - Semantator: semantic annotator for converting biomedical text to linked data.
AB  - More than 80% of biomedical data is embedded in plain text. The unstructured
      nature of these text-based documents makes it challenging to easily browse and
      query the data of interest in them. One approach to facilitate browsing and
      querying biomedical text is to convert the plain text to a linked web of data,
      i.e., converting data originally in free text to structured formats with defined
      meta-level semantics. In this paper, we introduce Semantator (Semantic
      Annotator), a semantic-web-based environment for annotating data of interest in
      biomedical documents, browsing and querying the annotated data, and interactively
      refining annotation results if needed. Through Semantator, information of
      interest can be either annotated manually or semi-automatically using plug-in
      information extraction tools. The annotated results will be stored in RDF and can
      be queried using the SPARQL query language. In addition, semantic reasoners can
      be directly applied to the annotated data for consistency checking and knowledge
      inference. Semantator has been released online and was used by the biomedical
      ontology community who provided positive feedbacks. Our evaluation results
      indicated that (1) Semantator can perform the annotation functionalities as
      designed; (2) Semantator can be adopted in real applications in clinical and
      transactional research; and (3) the annotated results using Semantator can be
      easily used in Semantic-web-based reasoning tools for further inference. 

PMID- 23867105
TI  - Immunological and autoimmune considerations of Autism Spectrum Disorders.
AB  - Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental
      conditions presenting in early childhood with a prevalence ranging from 0.7% to
      2.64%. Social interaction and communication skills are impaired and children
      often present with unusual repetitive behavior. The condition persists for life
      with major implications for the individual, the family and the entire health care
      system. While the etiology of ASD remains unknown, various clues suggest a
      possible association with altered immune responses and ASD. Inflammation in the
      brain and CNS has been reported by several groups with notable microglia
      activation and increased cytokine production in postmortem brain specimens of
      young and old individuals with ASD. Moreover several laboratories have isolated
      distinctive brain and CNS reactive antibodies from individuals with ASD. Large
      population based epidemiological studies have established a correlation between
      ASD and a family history of autoimmune diseases, associations with MHC complex
      haplotypes, and abnormal levels of various inflammatory cytokines and
      immunological markers in the blood. In addition, there is evidence that
      antibodies that are only present in some mothers of children with ASD bind to
      fetal brain proteins and may be a marker or risk factor for ASD. Studies
      involving the injection of these ASD specific maternal serum antibodies into
      pregnant mice during gestation, or gestational exposure of Rhesus monkeys to IgG
      subclass of these antibodies, have consistently elicited behavioral changes in
      offspring that have relevance to ASD. We will summarize the various types of
      studies associating ASD with the immune system, critically evaluate the quality
      of these studies, and attempt to integrate them in a way that clarifies the areas
      of immune and autoimmune phenomena in ASD research that will be important
      indicators for future research. 

PMID- 23867106
TI  - Dynamic obstruction of the left main coronary artery ostium by a papillary
      fibroelastoma.
AB  - BACKGROUND: Benign tumours of the heart are usually detected as incidental
      findings during echocardiography. Most cases are intracardiac tumours, with
      myxoma being the most frequent entity. We present images of a patient with acute
      myocardial infarction and a concomitant extracardiac benign tumour in the aortic
      root. METHODS: Transesophageal echocardiography, coronary computed tomography
      angiography, cardiac surgery and histology of the excised tumour were performed.
      RESULTS: A mobile mass was found in the aortic root obstructing the left main
      coronary artery ostium during diastole. Coronary CT angiography indicated severe
      coronary artery disease and the patient underwent bypass surgery and excision of
      the tumour. The excised tumour was identified as papillary fibroelastoma.
      CONCLUSIONS: Papillary fibroelastoma is the second most benign tumour of the
      heart. More than other tumours it is prone to embolization. Extracardiac location
      as in our case is very rare but dangerous since embolization may occur
      spontaneously or associated with catheterization.

PMID- 23867107
TI  - Revealing various coupling of electron transfer and proton pumping in
      mitochondrial respiratory chain.
AB  - Cellular respiration is the process that releases energy from food and supplies
      energy for life processes. The mitochondrial respiratory chain is the final and
      most important step for cellular respiration and is located on the inner membrane
      of mitochondrion and comprises four large trans-membrane protein complexes
      (respiratory chain Complexes I, II, III and IV) as well as ubiquinone between
      Complexes I/II and III and cytochrome c between Complexes III and IV. The
      function of mitochondrial respiratory chain is biological oxidation by
      transferring electrons from NADH and succinate to oxygen and then generating
      proton gradient across the inner membrane. Such proton gradient is utilized by
      ATP synthase (ATPase, also called as Complex V) to produce energy molecules ATP.
      Structural studies of mitochondrial respiratory membrane protein complexes are
      important to understand the mechanism of electron transfer and the redox-coupled
      proton translocation across the inner membrane. Here, according to the time line,
      we reviewed the great achievements on structural studies of mitochondrial
      respiratory complexes in the past twenty years as well as the recent research
      progresses on the structures of mitochondrial respiratory supra-complexes. 

PMID- 23867109
TI  - Gene conversions are under purifying selection in the carcinoembryonic antigen
      immunoglobulin gene families of primates.
AB  - The carcinoembryonic antigen (CEA) family contains a large number of
      glycoproteins belonging to the immunoglobulin superfamily. Here, we investigate
      whether the gene conversions occurring between primate CEA-related genes are
      adaptive. Our results show that primate CEA-related genes are subject to frequent
      and repeated gene conversion events. Furthermore, gene conversions occur most
      frequently between nearby genes sharing similar sequences, are not more frequent
      in Ig-like V-type 1 domains than in the Ig-like C2-type 1 domains and dN/dS ratio
      tests shown that both these domains evolve either neutrally or under purifying
      selection. Our results therefore suggest that CEA-related genes evolve under
      purifying selection and the frequent gene conversion events we observed likely
      represent selectively neutral events between genes having similar sequences and
      functions. 

PMID- 23867108
TI  - Developmental roles of Drosophila tRNA processing endonuclease RNase ZL as
      revealed with a conditional rescue system.
AB  - Drosophila RNase Z(L) (dRNaseZ) belongs to a family of endoribonucleases with a
      major role in tRNA 3'-end processing. The biochemical function of RNase Z(L) is
      conserved from yeast to human. Here we present a study of its biological function
      during Drosophila development. In flies, dRNaseZ provides a non-redundant
      function, as the RNZ(ED24) knockout (KO) mutation causes early larval lethality.
      Mosaic and conditional rescue techniques were employed to determine dRNaseZ
      requirements at later stages. We found that dRNaseZ activity is essential for all
      phases of fly development that involve cell division, including growth of adult
      tissue progenitors during larval and metamorphic stages, and gametogenesis in
      adults. At the cellular level, two major phenotypes were identified-cell growth
      deficiency in endoreplicating tissues and cell cycle arrest in mitotic tissues.
      While cell growth and proliferation are both dependant on protein synthesis, the
      two phenotypes displayed reliance on different dRNaseZ functions. We found that
      dRNaseZ KO completely blocks tRNA maturation without diminishing the abundance of
      mature tRNA molecules. Our data indicate that growth arrest of endoreplicating
      cells is primarily attributed to the relocation of the pool of mature tRNAs into
      the nuclei causing a decrease in translation efficiency. Mitotically dividing
      cells appear to be less dependent on translation machinery as they maintain their
      normal size when deprived of dRNaseZ activity, but rather display a cell cycle
      arrest at the G2-M transition. 

PMID- 23867111
TI  - A high-throughput functional complementation assay for classification of BRCA1
      missense variants.
AB  - Mutations in BRCA1 and BRCA2 account for the majority of hereditary breast and
      ovarian cancers, and therefore sequence analysis of both genes is routinely
      conducted in patients with early-onset breast cancer. Besides mutations that
      clearly abolish protein function or are known to increase cancer risk, a large
      number of sequence variants of uncertain significance (VUS) have been identified.
      Although several functional assays for BRCA1 VUSs have been described, thus far
      it has not been possible to conduct a high-throughput analysis in the context of
      the full-length protein. We have developed a relatively fast and easy cDNA-based
      functional assay to classify BRCA1 VUSs based on their ability to functionally
      complement BRCA1-deficient mouse embryonic stem cells. Using this assay, we have
      analyzed 74 unclassified BRCA1 missense mutants for which all predicted
      pathogenic variants are confined to the BRCA1 RING and BRCT domains.
      SIGNIFICANCE: BRCA1 VUSs are frequently found in patients with hereditary breast
      or ovarian cancer and present a serious problem for clinical geneticists. This
      article describes the generation, validation, and application of a reliable high
      throughput assay for the functional classification of BRCA1 sequence variants of
      uncertain significance.

PMID- 23867110
TI  - HIVID: an efficient method to detect HBV integration using low coverage
      sequencing.
AB  - We reported HIVID (high-throughput Viral Integration Detection), a novel
      experimental and computational method to detect the location of Hepatitis B Virus
      (HBV) integration breakpoints in Hepatocellular Carcinoma (HCC) genome. In this
      method, the fragments with HBV sequence were enriched by a set of HBV probes and
      then processed to high-throughput sequencing. In order to evaluate the
      performance of HIVID, we compared the results of HIVID with that of whole genome
      sequencing method (WGS) in 28 HCC tumors. We detected a total of 246 HBV
      integration breakpoints in HCC genome, 113 out of which were within 400bp
      upstream or downstream of 125 breakpoints identified by WGS method, covering
      89.3% (125/140) of total breakpoints. The integration was located in the gene
      TERT, MLL4, and CCNE1. In addition, we discovered 133 novel breakpoints missed by
      WGS method, with 66.7% (10/15) of validation rate. Our study shows HIVID is a
      cost-effective methodology with high specificity and sensitivity to identify
      viral integration in human genome. 

PMID- 23867112
TI  - Effectiveness of brief suicide management training programme for medical
      residents in Japan: a cluster randomized controlled trial.
AB  - Aims. To evaluate the effectiveness of a brief suicide management training
      programme for Japanese medical residents compared with the usual lecture on
      suicidality. Methods. In this multi-center, clustered randomized controlled
      trial, the intervention group attended a structured suicide management programme
      and the control group, the usual lecture on depression and suicidality. The
      primary outcome was the difference in residents' cumulative competency score to
      manage suicidal persons from baseline (T0) to 1 month after the intervention
      (T2), determined using the Suicide Intervention Response Inventory (SIRI-1)
      score, at individual level. Results. Analysis of 114 residents (intervention
      group n = 65, control group n = 49) assigned to two clusters in each group
      revealed no change in SIRI-1 score from T0 to T2 or immediately after the
      intervention (T1) between the two groups. As a secondary analysis, discrepancy in
      judgement between the participants and Japanese suicidologists was examined
      immediately after the intervention in the adjusted model, with a mean difference
      in score of 9.98 (95% confidence interval: 4.39-15.56; p = 0.001). Conclusions.
      The structured programme was not proven to improve competency in suicide
      management when measured by the SIRI-1 score. Further elaboration of the
      programme and valid measurement of its outcome would be needed to show the
      program's effectiveness. 

PMID- 23867113
TI  - A cost-effectiveness analysis of parecoxib in the management of postoperative
      pain in the Greek health care setting.
AB  - BACKGROUND: Postoperative pain management represents a significant factor of
      morbidity and reduced quality of life for patients, as well as a situation that
      substantially increases perioperative costs. Available analgesia treatments
      improve patient outcomes and reduce resource use associated with pain management,
      although with varying costs and adverse effects. OBJECTIVES: The aim of this
      analysis was to assess the costs and patient outcomes of parecoxib used in
      combination with opioids versus use of opioids alone (monotherapy) in the
      postoperative treatment of surgical patients in Greece. METHODS: A model
      comparing parecoxib plus opioid treatment versus opioids alone was developed that
      simulated the first 3 days postsurgery. Clinical efficacy was based on a Phase
      III, randomized, double-blind, clinical trial that also provided the frequencies
      of the occurrence of clinically meaningful events (CMEs) related to opioid use
      for both treatment arms. Resource use associated with each CME was elicited via
      strictly structured questionnaire-based interviews conducted by a panel of
      experts (surgeons and anesthesiologists), and costs were determined from the
      perspective of Social Insurance in Greece (2012 euros). Treatment effectiveness
      was calculated in summed pain intensity scores. A series of 1-way sensitivity
      analyses were conducted to check the robustness of the outcomes. RESULTS:
      Patients treated with parecoxib plus opioids had lower summed pain intensity
      scores (59.20 vs 80.80) and fewer CMEs (0.62 vs 1.04 per patient) compared with
      opioids alone for a 3-day period. This outcome led to a full offset of the excess
      cost of the addition of parecoxib and led to potential savings of ?858 per
      patient compared with opioid use alone. Savings were mainly attributable to
      decreased CMEs due to reduced intensive care unit and general ward bed-days as
      well as to reduced physician and nurse time. Results were sensitive with regard
      to probabilities of occurrence or co-occurrence of CMEs (>=2 CMEs occurring
      simultaneously), although only to a small extent. Medication costs had a minimal
      impact on the results of the sensitivity analysis. CONCLUSIONS: Parecoxib may be
      a useful addition to opioid treatment by improving postoperative analgesic
      management, reducing opioid-related adverse events, and lowering per-patient
      treatment costs.

PMID- 23867114
TI  - Warfarin use and stroke risk among patients with nonvalvular atrial fibrillation
      in a large managed care population.
AB  - BACKGROUND: Stroke prevention is a goal of atrial fibrillation (AF) management,
      but discontinuation of warfarin anticoagulation therapy is common. OBJECTIVE: To
      investigate the association between warfarin discontinuation and hospitalization
      for stroke among nonvalvular AF (NVAF) patients enrolled in managed care.
      METHODS: Patients with NVAF who initiated warfarin therapy from January 2005
      through June 2009 were included. Warfarin discontinuation was defined as a supply
      gap >60 days without evidence of International Normalized Ratio measurements.
      Follow-up, which was a variable time period from warfarin initiation until the
      earlier of death, disenrollment from the health plan, or June 30, 2010, was
      divided into periods of warfarin treatment and discontinuation. Stroke events
      were identified based on claims for inpatient stays with a primary diagnosis of
      stroke or transient ischemic attack. Cox proportional hazards models were
      constructed to assess the relationship between warfarin discontinuation and
      incident stroke while adjusting for baseline demographics, stroke and bleeding
      risk, and comorbidities, as well as time-dependent antiplatelet use, stroke, and
      bleeding events in the previous warfarin treatment period. RESULTS: Among
      warfarin initiators with NVAF (N = 16,253), 51.4% discontinued warfarin therapy
      at least once during a mean follow-up of 668 days. Stroke risk was significantly
      greater during warfarin discontinuation periods compared with therapy periods
      (hazard ratio = 1.60; 95% CI, 1.35-1.90; P < 0.001). CONCLUSIONS: More than half
      of patients on warfarin had treatment gaps or discontinued therapy. Therapy gaps
      were associated with increased stroke risk.

PMID- 23867115
TI  - Quantitative (1)H NMR method for hydrolytic kinetic investigation of salvianolic
      acid B.
AB  - This work presents an exploratory study for monitoring the hydrolytic process of
      salvianolic acid B (Sal B) in low oxygen condition using a simple quantitative
      (1)H NMR (Q-NMR) method. The quantity of the compounds was calculated by the
      relative ratio of the integral values of the target peak for each compound to the
      known amount of the internal standard trimethylsilyl propionic acid (TSP).
      Kinetic runs have been carried out on different initial concentrations of Sal B
      (5.00, 10.0, 20.0mg/mL) and temperatures of 70, 80, 90 degrees C. The effect of
      these two factors during the transformation process of Sal B was investigated.
      The hydrolysis followed pseudo-first-order kinetics and the apparent degradation
      kinetic constant at 80 degrees C decreased when concentration of Sal B increased.
      Under the given conditions, the rate constant of overall hydrolysis as a function
      of temperature obeyed the Arrhenius equation. Six degradation products were
      identified by NMR and mass spectrometric analysis. Four of these degradation
      products, i.e. danshensu (DSS), protocatechuic aldehyde (PRO), salvianolic acid D
      (Sal D) and lithospermic acid (LA) were further identified by comparing the
      retention times with standard compounds. The advantage of this Q-NMR method was
      that no reference compounds were required for calibration curves, the
      quantification could be directly realized on hydrolyzed samples. It was proved to
      be simple, convenient and accurate for hydrolytic kinetic study of Sal B. 

PMID- 23867116
TI  - [Nutritional assessment and treatment of sarcopenia].

PMID- 23867117
TI  - Associations between polymorphisms in sex steroid related genes and autistic-like
      traits.
AB  - Sex differences in psychiatric disorders are common, which is particularly
      striking in autism spectrum disorders (ASDs) that are four times more prevalent
      in boys. High levels of testosterone during early development have been
      hypothesized to be a risk factor for ASDs, supported by several studies showing
      fetal testosterone levels, as well as indirect measures of prenatal
      androgenization, to be associated with ASDs and autistic-like traits (ALTs).
      Further, the importance of sex steroid related genes in ASDs is supported by
      studies reporting associations between polymorphisms in genes involved in sex
      steroid synthesis/metabolism and ASDs and ALTs. The aim of the present study was
      to investigate possible associations between 29 single nucleotide polymorphisms
      (SNPs) in eight genes related to sex steroids and autistic features. Individuals
      included in the study belong to a subset (n=1771) from The Child and Adolescent
      Twin Study in Sweden (CATSS), which are all assessed for ALTs. For two SNPs,
      rs2747648 located in the 3'-UTR of ESR1 encoding the estrogen receptor alpha and
      rs523349 (Leu89Val) located in SRD5A2 encoding 5-alpha-reductase, type 2, highly
      significant associations with ALTs were found in boys and girls, respectively.
      The results of the present study suggest that SNPs in sex steroid related genes,
      known to affect gene expression (rs2747648 in ESR1) and enzymatic activity
      (Leu89Val in SRD5A2), seem to be associated with ALTs in a general population. In
      conclusion, the current findings provide further support for a role of sex
      steroids in the pathophysiology of ASDs.

PMID- 23867118
TI  - Methodological considerations in use of the cortisol/DHEA(S) ratio in adolescent
      populations.
AB  - OBJECTIVE: The cortisol/DHEA(S) ratio has demonstrated utility in studies of HPA
      activity and psychopathology. However, use of the cortisol/DHEA(S) ratio in
      adolescent populations requires additional consideration of differential changes
      in DHEA(S) and cortisol during the course of puberty. This study examines the
      relationship between pubertal status and individual cortisol and DHEAS levels as
      well as with the cortisol/DHEAS ratio. METHOD: Morning salivary cortisol and
      urinary DHEAS levels were obtained for 267 young adolescents at three time
      points, each approximately one year apart. Growth curve modeling and repeated
      measures ANOVA were used to assess the effect of adrenal development on
      individual hormone levels and on the total ratio. RESULTS: Pubic hair development
      was a significant predictor of change over time in DHEAS but not cortisol.
      Development was also a significant predictor of the cortisol/DHEAS ratio when raw
      cortisol and DHEAS values were used. CONCLUSIONS: Our findings indicate that,
      when DHEAS levels were adjusted to control for pubertal status, the ratio
      demonstrated stability over time. This finding is in line with the hypothesis
      that the ratio may tap stable individual differences in HPA functioning.

PMID- 23867119
TI  - Urinary carcinogenic 4-6 ring polycyclic aromatic hydrocarbons in coke oven
      workers and in subjects belonging to the general population: role of occupational
      and environmental exposure.
AB  - AIM: A new solid phase microextraction-gas chromatography-mass spectrometry
      method (SPME-GC-MS) to detect urinary unmetabolized 3-, 6-ring polycyclic
      aromatic hydrocarbons (PAHs) was applied to coke oven workers and general
      population subjects with the aim to assess exposure to carcinogenic PAHs, to
      evaluate the role of occupational and environmental variables on PAHs levels, and
      to compare present results with those previously obtained with a less sensitive
      method. METHODS: A total of 104 coke oven workers (CW) from Poland [recruited in
      2000 (CW-2000; n=55) and 2006 (CW-2006; n=49)], and 45 control subjects from the
      same area, provided urine spot samples for measurement of 10 PAHs (from
      phenanthrene to benzo[g,h,i]perylene). The comparison between the two methods was
      performed only on CW-2000 subjects. Information regarding personal
      characteristics and job variables was collected by a questionnaire. RESULTS: The
      new method enables the quantification of 5-, 6-ring PAHs; precision and accuracy
      were in the 7.3-20.8% and 89.4-110% range, respectively; in CW-2000 samples
      results obtained with the new and the old method were highly correlated (Lin's
      concordance correlation coefficients: from 0.790 to 0.965); the mean difference
      between measured PAHS increased with the molecular weight of the analytes (from
      +5 to +27%). Urinary PAHs were above or equal to the quantification limit,
      depending on the compound, in 67-100% (min-max), 26-100% and 6-100% of samples
      from CW-2000, CW-2006 and controls, respectively. Chrysene and benz[a]anthracene
      were the most abundant carcinogenic PAHs with median levels of 43.4, 13.4, and
      2.3 ng/L and 45.9, 14.9, and 0.7 ng/L in CW-2000, CW-2006, and controls,
      respectively, while benzo[a]pyrene levels were 6.5, 0.7 and <0.5 ng/L. The
      multiple linear regression model showed that the determinants of exposure were
      the use of wood and/or coke for house heating for controls, and job title or the
      plant for CW-2006. CONCLUSIONS: Urinary benzo[a]pyrene and other carcinogenic
      PAHs were, for the first time, quantified in urine samples from both
      occupationally and environmentally exposed subjects. These results show that
      urinary PAHs can discriminate exposure at different levels. Moreover, the
      simultaneous determination of several PAHs allows for the development of
      excretion profiles to assess exposure to specific compounds.

PMID- 23867120
TI  - A pilot study on the prevalence of maternal obesity in selected Greek counties.
AB  - OBJECTIVE: To report a pilot prevalence of maternal overweight, obesity and
      underweight in selected Greek counties. METHODS: A total of 441 adult
      childbearing women were recruited from maternity clinics in 6 Greek counties for
      this cross-sectional study. Pre-gravid weight status was defined according to the
      WHO cut-offs and gravid weight status was diagnosed with the Mardones and Rosso
      weight gain chart. RESULTS: During gestation the majority of the participants
      were of normal body weight (BW) (34.0%), obesity was apparent in 25.6% of the
      sample, 23.8% of the participants were underweight, and the remaining 16.6% were
      overweight. Overall, pregnancy tripled the prevalence of underweight, increased
      the prevalence of obesity (by 388.0%) and decreased the number of participants in
      the normal BW category (p<=0.001 for all). The majority of participants
      classified in each pre-gravid weight-category remained in the same weight
      category during their gestation. All the pre-gravidly obese women were also obese
      during pregnancy. Underweight was more prevalent in Kavala (37.5%) and obesity
      was more frequent in Thessaloniki (30.8%). Women who were overweight prior to
      conception were highly likely to be overweight/obese during pregnancy (OR: 23.8,
      CI: 11.1-51.0). CONCLUSIONS: The results indicate a high prevalence of
      overweight, obesity and underweight among pregnant women in Greece.

PMID- 23867121
TI  - Dynamics of milk leukocytes in response to a biological response modifier during
      bovine subclinical mastitis.
AB  - The objective of this study was to evaluate the dynamics of milk leukocyte in
      response to intramammary infusion of a biological response modifier (BRM)
      prepared from Nocardia globerula during bovine subclinical mastitis (SCM). The
      somatic cell count (SCC), total bacterial count (TBC) in milk, cyclooxygenase
      (COX) activity, phagocytic activity, production of hydrogen peroxide (H2O2) and
      myeloperoxidase (MPO) activity in milk leukocytes were evaluated after
      intramammary infusion of BRM in quarters inflicted with SCM. Intramammary
      infusion of BRM significantly enhanced the SCC in earlier phase with subsequent
      reduction on day 7 after initiation of treatment. Similarly, the COX activity in
      milk cell lysate increased on day 3 and reduced on day 5. However reduction in
      TBC could be observed from day 3 onwards. The phagocytic activity of milk
      leukocytes was lower in mastitic cows whereas, significant enhancement in
      phagocytic activity was recorded in post treated cows with BRM. Similarly, the
      H2O2 production and MPO activities in milk leukocytes were enhanced significantly
      in diseased cows in response to BRM infusion. Significant enhancement of
      phagocytic activity, H2O2 and MPO activities indicate the priming of resident
      milk leukocytes in response to BRM infusion. Initial influx of SCC and raised COX
      activity also indicate the immunomodulatory activity of BRM. Reduction of TBC
      could be due to increased leukocytosis or direct microbicidal activity of
      activated milk cells. In the present study, the biological activity of BRM at
      standardized dose against bovine SCM is reported for the first time. Development
      of such therapy is warranted to reduce the drug resistance of microorganisms and
      contamination of milk with antibiotic residue. 

PMID- 23867122
TI  - An approach for reliability analysis of industrial systems using PSO and IFS
      technique.
AB  - The main objective of this paper is to present a technique for computing the
      membership functions of the intuitionistic fuzzy set (IFS) by utilizing
      imprecise, uncertain and vague data. In literature so far, membership functions
      of IFS are computed via using fuzzy arithmetic operations within collected data
      and hence contain a wide range of uncertainties. Thus it is necessary for
      optimizing these spread by formulating a nonlinear optimization problem through
      ordinary arithmetic operations instead of fuzzy operations. Particle swarm
      optimization (PSO) has been used for constructing their membership functions.
      Sensitivity as well as performance analysis has also been conducted for finding
      the critical component of the system. Finally the computed results are compared
      with existing results. The suggested framework has been illustrated with the help
      of a case. 

PMID- 23867123
TI  - Adverse impact of regional lymph node involvement in osteosarcoma.
AB  - BACKGROUND: Metastatic dissemination in osteosarcoma occurs haematogenously,
      though regional lymph node involvement is rarely reported. We investigated
      incidence, patient characteristics and survival for patients with osteosarcoma
      and regional lymph node involvement at diagnosis. METHODS: We identified 2748
      cases of high-grade osteosarcoma with available information regarding regional
      lymph node involvement in the Surveillance Epidemiology and End Results database
      from 1973 to 2009. Demographics were compared using chi-squared tests or t-tests.
      Overall survival was estimated using Kaplan-Meier method and compared with log
      rank tests. Multivariate analysis of overall survival was performed using Cox
      proportional hazards methods. RESULTS: There were 74 patients (2.7%) with
      regional lymph node involvement at diagnosis of whom 19 (0.7%) were
      pathologically confirmed. Patients with regional node involvement were more
      likely to have extraskeletal tumours, distant metastases, tumours arising outside
      the lower extremity (p<0.0001 for all comparisons) and larger tumours (p=0.033).
      Five-year overall survival in those with and without regional node involvement
      was 10.9% (95% confidence interval (CI) 4.6-20.4) and 54.3% (95% CI 52.2-56.4;
      p<0.0001). In multivariate analysis, regional node involvement remained
      predictive of inferior survival after controlling for differences in metastatic
      status, age, tumour site and extraskeletal origin (hazard ratio 2.05, 95% CI 1.57
      2.67; p<0.0001). Similar survival results were found when the analysis was
      restricted to patients with pathologically confirmed positive or negative
      regional lymph nodes. CONCLUSION: This analysis confirms that regional node
      involvement is a significant adverse prognostic factor that is independent of
      metastatic status, extraskeletal origin, age and tumour site.

PMID- 23867124
TI  - Simultaneous targeting of insulin-like growth factor-1 receptor and anaplastic
      lymphoma kinase in embryonal and alveolar rhabdomyosarcoma: a rational choice.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is an aggressive soft tissue tumour mainly
      affecting children and adolescents. Since survival of high-risk patients remains
      poor, new treatment options are awaited. The aim of this study is to investigate
      anaplastic lymphoma kinase (ALK) and insulin-like growth factor-1 receptor (IGF
      1R) as potential therapeutic targets in RMS. PATIENTS AND METHODS: One-hundred
      and-twelve primary tumours (embryonal RMS (eRMS)86; alveolar RMS (aRMS)26) were
      collected. Expression of IGF-1R, ALK and downstream pathway proteins was
      evaluated by immunohistochemistry. The effect of ALK inhibitor NVP-TAE684
      (Novartis), IGF-1R antibody R1507 (Roche) and combined treatment was investigated
      by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in
      cell lines (aRMS Rh30, Rh41; eRMS Rh18, RD). RESULTS: IGF-1R and ALK expression
      was observed in 72% and 92% of aRMS and 61% and 39% of eRMS, respectively. Co
      expression was observed in 68% of aRMS and 32% of eRMS. Nuclear IGF-1R expression
      was an adverse prognostic factor in eRMS (5-year survival 46.9 +/- 18.7% versus
      84.4 +/- 5.9%, p=0.006). In vitro, R1507 showed diminished viability
      predominantly in Rh41. NVP-TAE684 showed diminished viability in Rh41 and Rh30,
      and to a lesser extent in Rh18 and RD. Simultaneous treatment revealed
      synergistic activity against Rh41 and Rh30. CONCLUSION: Co-expression of IGF-1R
      and ALK is detected in eRMS and particularly in aRMS. As combined inhibition
      reveals synergistic cytotoxic effects, this combination seems promising and needs
      further investigation.

PMID- 23867125
TI  - Upfront adjuvant aromatase inhibitors in women with lobular breast cancer.

PMID- 23867126
TI  - Adult weight change and risk of colorectal cancer in the European Prospective
      Investigation into Cancer and Nutrition.
AB  - AIM: Weight change during adult life may reflect metabolic changes and influence
      colorectal cancer (CRC) development, but such role is not well established. We
      aimed to explore the association between adult weight change (from age 20 to 50)
      and CRC risk. In particular, we investigated differences according to colon and
      rectal cancer, sex and measures of attained adiposity. METHODS: We included
      201,696 participants from six participating countries in the European Prospective
      Investigation into Cancer and Nutrition (1992-2010). During a mean follow-up of
      11.2 years 2384 (1194 in men and 1190 in women) incident CRC cases occurred. Cox
      proportional hazard models adjusted for body mass index at age 20 and lifestyle
      factors at study recruitment were used to calculate hazard ratios (HRs) and 95%
      confidence intervals (CIs). RESULTS: After multivariable adjustment, each kg of
      weight gained annually from age 20 to 50 was associated with a 60% higher risk of
      colon cancer (95% CI 1.20-2.09), but not rectal cancer (HR 1.13, 95% CI 0.79
      1.62, P(interaction)=0.04). The higher risk of colon cancer was restricted to
      people with high attained waist circumference at age 50 (HR 1.82, 95%CI 1.14
      2.91, P(interaction)=0.02). Results were not different in men and women
      (P(interaction)=0.81). CONCLUSION(S): Adult weight gain, as reflected by attained
      abdominal obesity at age 50, increases colon cancer risk in both men and women.
      These data underline the importance of weight management and metabolic health
      maintenance in early adult life years for colon cancer prevention.

PMID- 23867127
TI  - Body composition and survival in the early clinical trials setting.
AB  - PURPOSE: Delineate the relationships between body composition parameters, 90-day
      mortality and overall survival, and correlate them with known prognostic factors
      in an early clinical trials clinic. PATIENTS AND METHODS: We studied 306
      consecutive patients with various tumours; body composition was analysed by
      computerised tomography images. Survival was measured from the first clinic
      visit, at 90-day period and until death/last follow-up visit. RESULTS: Median
      patient age was 56 years; 159 patients were men. Ninety-day mortality rate was
      12%. Median overall survival was 9 months. In multivariate analyses, high MD
      Anderson Cancer Center (MDACC) score (p < 0.0001) [lactate dehydrogenase (LDH) >
      normal, albumin < normal, Eastern Cooperative Oncology Group (ECOG) performance
      status > 1, metastatic sites > 2, gastrointestinal (GI) tumours], low skeletal
      muscle index (SMI) (p = 0.0406) and male gender (p = 0.0077) were independent
      predictors of poor survival. If Royal Marsden Hospital (RMH) score (LDH > normal,
      albumin<normal, metastatic sites > 2) was used in lieu of MDACC score, it was
      also significant (p = 0.0003). Including SMI and gender in the MDACC or RMH score
      improved the accuracy of the original model (p = 0.006 and p = 0.0037,
      respectively). CONCLUSION: Patients with low SMI have shorter survival. Gender
      and SMI strengthens the accuracy of MDACC or RMH scores as prognostic tools.
      Prospective validation of these findings is warranted.

PMID- 23867128
TI  - Response to letter.

PMID- 23867130
TI  - Patient-reported outcomes of cirrhosis.

PMID- 23867129
TI  - Epidermal growth factor receptor expression in laryngeal cancer predicts the
      effect of hypoxia modification as an additive to accelerated radiotherapy in a
      randomised controlled trial.
AB  - Accelerated radiotherapy (AR) improves the poor prognosis associated with
      epidermal growth factor receptor (EGFR) overexpression frequently seen in head
      and neck carcinomas. Combining AR with carbogen and nicotinamide (ARCON)
      counteracts enhanced tumour cell proliferation- and hypoxia-related
      radioresistance. The purpose of this study was to investigate if EGFR expression
      levels are associated with response to ARCON in patients with carcinoma of the
      larynx. Patients (N=272) with advanced stage larynx carcinoma were randomised
      between AR alone and ARCON. Paraffin-embedded biopsies from these patients were
      processed for immunohistochemical staining of EGFR. EGFR fraction was quantitated
      by automated image analysis and related to clinical outcome. A large variation
      was observed in EGFR fraction between tumours with expression levels ranging from
      0 to 0.93 (median fraction 0.4). No difference in 5-year locoregional control was
      found between low and high EGFR expressing tumours in the AR arm (69% versus
      75%), which is in line with the established effect of AR in EGFR overexpressing
      tumours. There was, however, a significant association in the ARCON arm: patients
      with low EGFR levels had a better 5-year locoregional control (88% versus 72%
      p=0.02) and disease-specific survival (92% versus 77% p=0.01). ARCON improved
      locoregional control relative to AR only in patients with low EGFR expression
      (hazard ratio (HR) 0.34 p=0.009). In conclusion, only in tumours with a low EGFR
      fraction, adding hypoxia modification to AR has an additive beneficial effect on
      outcome. EGFR expression is a predictive biomarker for the selection of patients
      that will or will not respond to ARCON. 

PMID- 23867131
TI  - A comparison of the behavioral and anatomical outcomes in sub-acute and chronic
      spinal cord injury models following treatment with human mesenchymal precursor
      cell transplantation and recombinant decorin.
AB  - This study assessed the potential of highly purified (Stro-1(+)) human
      mesenchymal precursor cells (hMPCs) in combination with the anti-scarring protein
      decorin to repair the injured spinal cord (SC). Donor hMPCs isolated from spinal
      cord injury (SCI) patients were transplanted into athymic rats as a suspension
      graft, alone or after previous treatment with, core (decorin(core)) and
      proteoglycan (decorin(pro)) isoforms of purified human recombinant decorin.
      Decorin was delivered via mini-osmotic pumps for 14 days following sub-acute (7
      day) or chronic (1 month) SCI. hMPCs were delivered to the spinal cord at 3 weeks
      or 6 weeks after the initial injury at T9 level. Behavioral and anatomical
      analysis in this study showed statistically significant improvement in functional
      recovery, tissue sparing and cyst volume reduction following hMPC therapy. The
      combination of decorin infusion followed by hMPC therapy did not improve these
      measured outcomes over the use of cell therapy alone, in either sub-acute or
      chronic SCI regimes. However, decorin infusion did improve tissue sparing, reduce
      spinal tissue cavitation and increase transplanted cell survivability as compared
      to controls. Immunohistochemical analysis of spinal cord sections revealed
      differences in glial, neuronal and extracellular matrix molecule expression
      within each experimental group. hMPC transplanted spinal cords showed the
      increased presence of serotonergic (5-HT) and sensory (CGRP) axonal growth within
      and surrounding transplanted hMPCs for up to 2 months; however, no evidence of
      hMPC transdifferentiation into neuronal or glial phenotypes. The number of hMPCs
      was dramatically reduced overall, and no transplanted cells were detected at 8
      weeks post-injection using lentiviral GFP labeling and human nuclear antigen
      antibody labeling. The presence of recombinant decorin in the cell
      transplantation regimes delayed in part the loss of donor cells, with small
      numbers remaining at 2 months after transplantation. In vitro co-culture
      experiments with embryonic dorsal root ganglion explants revealed the growth
      promoting properties of hMPCs. Decorin did not increase axonal outgrowth from
      that achieved by hMPCs. We provide evidence for the first time that (Stro-1(+))
      hMPCs provide: i) an advantageous source of allografts for stem cell
      transplantation for sub-acute and chronic spinal cord therapy, and (ii) a
      positive host microenvironment that promotes tissue sparing/repair that
      subsequently improves behavioral outcomes after SCI. This was not measurably
      improved by recombinant decorin treatment, but does provide important information
      for the future development and potential use of decorin in contusive SCI therapy.

PMID- 23867132
TI  - Zinc ionophores pyrithione inhibits herpes simplex virus replication through
      interfering with proteasome function and NF-kappaB activation.
AB  - Pyrithione (PT), known as a zinc ionophore, is effective against several
      pathogens from the Streptococcus and Staphylococcus genera. The antiviral
      activity of PT was also reported against a number of RNA viruses. In this paper,
      we showed that PT could effectively inhibit herpes simplex virus types 1 and 2
      (HSV-1 and HSV-2). PT inhibited HSV late gene (Glycoprotein D, gD) expression and
      the production of viral progeny, and this action was dependent on Zn(2+). Further
      studies showed that PT suppressed the expression of HSV immediate early (IE)
      gene, the infected cell polypeptide 4 (ICP4), but had less effect on another
      regulatory IE protein, ICP0. It was found that PT treatment could interfere with
      cellular ubiquitin-proteasome system (UPS), leading to the inhibition of HSV-2
      induced IkappaB-alpha degradation to inhibit NF-kappaB activation and enhanced
      promyelocytic leukemia protein (PML) stability in nucleus. However, PT did not
      show direct inhibition of 26S proteasome activity. Instead, it induced Zn(2+)
      influx, which facilitated the dysregulation of UPS and the accumulation of
      intracellular ubiquitin-conjugates. UPS inhibition by PT caused disruption of
      IkappaB-alpha degradation and NF-kappaB activation thus leading to marked
      reduction of viral titer. 

PMID- 23867133
TI  - The helicase-primase inhibitor BAY 57-1293 reduces the Alzheimer's disease
      related molecules induced by herpes simplex virus type 1.
AB  - Herpes simplex virus type 1 (HSV1) infection of cultured cells causes the
      formation of beta-amyloid (Abeta) and abnormal tau (P-tau). These molecules
      comprise the main components of the abnormal protein deposits, amyloid plaques
      and neurofibrillary tangles, respectively, in Alzheimer's disease (AD) brains,
      and they have been implicated in disease development. The formation of P-tau, but
      not of Abeta, depends on viral DNA replication, but nonetheless, three antiviral
      agents that inhibit HSV1 DNA replication, including acyclovir (ACV), were found
      to reduce greatly the level of Abeta as well as P-tau, the former probably
      through prevention of viral spread. Previous studies showed that HSV1 DNA is
      present and is active in the brain of many elderly people, including AD patients,
      and that in combination with the type 4 allele of the apolipoprotein E gene, it
      is likely to play a role in the disease, perhaps via Abeta and P-tau production.
      With the aim of finding the most suitable antiviral for inhibiting Abeta and P
      tau formation as well as HSV1 DNA replication, for future use in a clinical trial
      for treating AD, we compared the efficacy of ACV with that of another antiviral,
      BAY 57-1293, which acts by a different mechanism from ACV. We found that BAY 57
      1293 is more efficient than ACV not only in inhibiting HSV1 replication,
      confirming previous studies, but also in decreasing Abeta and P-tau formation.
      Also, the cell clusters that are formed during infection are reduced in size much
      more efficiently by BAY 57-1293 than by ACV. These data suggest that BAY 57-1293
      would be a more effective agent than ACV for treating AD. 

PMID- 23867135
TI  - Update of the echocardiography core syllabus of the European Association of
      Cardiovascular Imaging (EACVI).
AB  - The update of the Echocardiography Core Syllabus of European Association of
      Cardiovascular Imaging (EACVI) is now available online. The Echocardiography Core
      Syllabus enumerates the elements of knowledge to be taught, represents a
      framework for the development of local training curricula and provides expected
      learning outcomes to the echocardiography learner. 

PMID- 23867134
TI  - Environmental perturbation, inflammation and behavior in healthy and virus
      infected mice.
AB  - The development of so-called "sickness behaviors" (e.g., anorexia, anhedonia,
      reduced social interaction, fatigue) during infectious and inflammatory disease
      has been linked to facets of the immune response. Such problems can be
      particularly troublesome during chronic latent infection, as the host immune
      system must employ continual vigilance to maintain viral latency. Epstein-Barr
      virus (EBV) is a ubiquitous human gamma-herpesvirus that causes acute disease and
      establishes life-long latency in people. Murine gammaherpesvirus (MuGHV) is a
      natural pathogen of wild rodents that provides an experimental model for studying
      the pathophysiology of an EBV-like gamma-herpesvirus in mice. To evaluate this
      model with regard to sickness behavior and its exacerbation during a chronic
      latent viral disease, we exposed uninfected and MuGHV-infected C57BL/6J and
      BALB/cByJ mice to novel and potentially stressful environmental perturbations and
      measured the impact of these challenges on behavior and markers of inflammation.
      The data indicate that exposure of mice to environmental perturbations during the
      normal somnolent phase is associated with reduced activity during the subsequent
      active phase, despite an intervening rest period. Effects on inflammatory
      mediators were complex due to independent and interactive effects of infection
      status, mouse strain, and exposure to stressful environment. However, GCSF and
      MCP1 were consistently elevated in lung both immediately after and 12h after
      exposure to a "dirty" cage containing the resident mouse (DCR); this increase
      occurred in both C57BL/6J and BALB/cByJ mice and was independent of infection
      status. At 12h after DCR, IL1beta and IP10 were also consistently elevated in
      lung. In response to DCR, BALB/cByJ mice showed a greater number of significant
      cytokine effects than did C57BL/6J mice. With regard to infection status, IP10
      was consistently elevated in lung at both time points regardless of mouse strain
      or DCR exposure. Several analytes were affected by mouse strain in serum or lung
      at one or both time points, with most strain differences present in serum at E18.
      Taken together, the data show that exposure of mice to environmental
      perturbations is associated with systemic inflammation that is in part
      independent of genetic background or latent MuGHV infection and with reduced
      activity that could represent fatigue, depression, or other facets of sickness
      behavior. 

PMID- 23867136
TI  - Ventricular response to dobutamine stress relates to the change in peak oxygen
      uptake during the 5-year follow-up in young patients with repaired tetralogy of
      Fallot.
AB  - AIMS: To evaluate the additional value of dobutamine stress testing in patients
      with repaired tetralogy of Fallot (TOF) by relating stress imaging parameters at
      baseline to relevant parameters of clinical condition and right ventricular (RV)
      size during a serial follow-up. METHODS AND RESULTS: We prospectively included 27
      patients (14 +/- 4 years at baseline), who were studied twice with a 5-year
      interval. Patients underwent cardiovascular magnetic resonance imaging to assess
      RV systolic and diastolic function at rest and during dobutamine stress. Normal
      response to dobutamine was defined as a decrease in RV end-systolic volume, and a
      increase in RV ejection fraction (EF) during stress. Exercise testing and
      electrocardiography were performed to determine peak oxygen uptake (peak VO2),
      QRS duration, and QT interval corrected for heart rate (QTc) interval. RV
      volumes, QRS duration, and QTc interval increased significantly from baseline to
      follow-up; peak VO2 tended to decrease (95 +/- 20-89 +/- 14%, P = 0.086).
      Response to dobutamine was normal in 26 of 27 patients and remained stable during
      the follow-up [relative increase in RVEF during stress: +25 +/- 9% (baseline) vs.
      +27 +/- 10% (follow-up)]. A smaller relative increase in RVEF during stress at
      baseline related to a larger relative decrease in peak VO2 during the follow-up
      (r = 0.59, P = 0.004). No significant associations were found with the relative
      increase in QRS duration, QTc interval, or RV end-diastolic volume during a 5
      year follow-up. CONCLUSION: In a young TOF population, response to dobutamine
      stress was normal and remained stable during the 5-year follow-up. A smaller
      increase in RVEF during stress at baseline was predictive for a larger decrease
      in peak VO2 during the 5-year follow-up.

PMID- 23867137
TI  - Sexual risk behavior and STI health literacy among ethnic minority adolescent
      women.
AB  - Although information is available for prevention of sexually transmitted
      infection (STI/HIV), adolescents continue to engage in high risk sexual behavior
      particularly ethnic minority adolescent women with histories of STI or abuse. A
      description therefore of STI/HIV knowledge and sexual risk behavior among these
      women is indicated for modification of prevention efforts for sexual health
      promotion. African-American (n=94) and Mexican-American (n=465) adolescent women
      14-18 years of age were included in the study. Assessments of sexual risk
      behavior and STI/HIV knowledge among these adolescent women described Mexican
      American women as at higher risk of STI, pregnancy, substance use and abuse with
      lower levels of STI/HIV knowledge, previous HIV testing and perceptions of risk
      than African-American women. A focus on Mexican-American adolescent women with
      histories of STI and abuse is indicated for translation of community-based health
      promotion interventions for amelioration of potential adverse sexual health
      outcomes among ethnic minority adolescent women.

PMID- 23867138
TI  - Factors contributing to the use of complementary and alternative medicine in
      rural older women with chronic pain in South Korea.
AB  - AIM: The aim of this study was to assess the prevalence of complementary and
      alternative medicines (CAM) use for managing pain and to investigate the factors
      predictive of current CAM use among rural older women in South Korea. BACKGROUND:
      Access to medical care among older adults in rural areas is poorer than in urban
      areas. METHODS: A cross-sectional descriptive study with a stratified sample of
      139 women aged over 65 with chronic pain residing in rural areas of Jeju Island,
      South Korea. A self-reported questionnaire was used to collect data. RESULTS:
      Most subjects reported using at least one type of CAM for relieving pain within
      the past 12 months. Almost half of them reported currently using CAM. Herbs were
      the most commonly used CAM. Only 'severity of pain' was presently associated with
      an increased use of CAM. CONCLUSION: It is imperative to take socio-geographic
      cultural factors into consideration when planning health promotion programs and
      caring for clients.

PMID- 23867139
TI  - Sural nerve defects after nerve biopsy or nerve transfer as a sensory
      regeneration model for peripheral nerve conduit implantation.
AB  - Nerve repair after injury can be effectively accomplished by direct suture
      approximation of the proximal and distal segments. This is more successful if
      coadaptation can be achieved without tension. Currently, the gold standard repair
      of larger deficits is the transplantation of an autologous sensory sural nerve
      graft. However, a significant disadvantage of this technique is the inevitable
      donor morbidity (sensory loss, neuroma and scar formation) after harvesting of
      the sural nerve. Moreover, limitation of autologous donor nerve length and fixed
      diameter of the available sural nerve are major drawbacks of current autograft
      treatment. Another approach that was introduced for nerve repair is the
      implantation of alloplastic nerve tubes made of, for example, poly-L-lactide. In
      these, nerve stumps of the transected nerves are surgically bridged using the
      biosynthetic conduit. A number of experimental studies, primarily in rodents,
      indicate axonal regeneration and remyelination after implantation of various
      conduits. However, only limited clinical studies with conduit implantation have
      been performed in acute peripheral nerve injuries particularly on digital nerves.
      Clinical transfer of animal studies, which can be carefully calibrated for site
      and extent of injury, to humans is difficult to interpret due to the intrinsic
      variability in human nerve injuries. This prevents effective quantification of
      improvement and induces bias in the study. Therefore, standardization of
      lesion/repair in human studies is warranted. Here we propose to use sural nerve
      defects, induced due to nerve graft harvesting or from diagnostic nerve biopsies
      as a model site to enable standardization of nerve conduit implantation. This
      would help better with the characterization of the implants and its effectiveness
      in axonal regeneration and remyelination. Nerve regeneration can be assessed, for
      example, by recovery of sensation, measured non-invasively by threshold to von
      Frey filaments and cold allodynia. Moreover, the implantation of nerve conduits
      may not only serve as a model to examine nerve repair, but it could also prevent
      neuroma formation, which is a major morbidity of sural nerve extraction.

PMID- 23867140
TI  - The credibility of the FDA.

PMID- 23867141
TI  - Preliminary assessment of the psychometric properties of the abridged Arabic
      version of the Zarit Burden Interview among caregivers of cancer patients.
AB  - PURPOSE: The Zarit Burden Interview (ZBI) is one of the most commonly used
      measures of caregiver burden. Although it has been translated into and validated
      in many languages, an Arabic version of the scale was lacking. This study
      examines the psychometric properties and factor structure of an abridged Arabic
      version of this measure-the ZBI-A-among caregivers of cancer patients. METHODS: A
      total of 96 caregivers completed a questionnaire consisting of the ZBI-A, the
      Hamilton Depression Rating Scale, the World Health Organization Well-Being Index
      and the Emotional Exhaustion subscale of the Maslach Burnout Inventory. The ZBI-A
      was assessed using exploratory factor analysis (EFA). Concurrent validity was
      also examined. RESULTS: The EFA supported a two-factor structure identical to
      that of the original ZBI scale. Concurrent validity was supported by the ZBI-A's
      significant negative association with caregiver well-being and positive
      association with depression and emotional exhaustion. CONCLUSION: These findings
      suggest that this abridged Arabic version of the Zarit Burden Interview is
      appropriate for use for assessing caregiving burden.

PMID- 23867142
TI  - [Appropriateness of antibiotic prescribing in a primary care area: a cross
      sectional study].
AB  - OBJECTIVE: To assess the profile of patients receiving antibiotics and the
      appropriateness of these prescriptions for the clinical conditions. METHODS: 
      DESIGN: Cross-sectional study of prescription-indication. SETTING: A primary
      health care area in Andalusia. SUBJECTS: Patients assigned to primary care
      centres. Patients with antibiotic prescriptions during 2009 were selected by
      simple random sampling (confidence level: 95%, accuracy: 5%). Primary endpoint:
      appropriateness of antibiotics prescribing to recommendations included in local
      guidelines. Data were obtained through the billing computerised prescriptions
      system and medical histories. RESULTS: Twenty-five per cent of the population
      area received antibiotics during 2009. The 1,266 patient samples showed the
      following characteristics: 57.9% were women, with a mean age of 41 (+/-1) years.
      There were 39.3% pensioners. The percentage of appropriate antibiotic
      prescriptions was 19.9%, with no difference due to gender. Statistically
      significant differences were related to age, being those over 65 years the group
      of patients with the highest percentage of inappropriateness. The main reasons
      for inappropriateness were: no recording of the infectious process (44.5%), a
      wrong treatment duration (15.5%), and the use of an inadequate antibiotic
      (11.5%). CONCLUSION: There is a high level of inappropriateness in antibiotic
      prescribing in primary care. The high level of under-recording of diagnoses,
      mainly in elderly patients, followed by the use of wrong schedules, and the wrong
      type of antibiotics were the main reasons of inappropriateness.

PMID- 23867143
TI  - N,N-dimethyl-p-toluidine, a component in dental materials, causes hematologic
      toxic and carcinogenic responses in rodent model systems.
AB  - Because of the potential for exposure to N,N-dimethyl-p-toluidine (DMPT) in
      medical devices and the lack of toxicity and carcinogenicity information
      available in the literature, the National Toxicology Program conducted toxicity
      and carcinogenicity studies of DMPT in male and female F344/N rats and B6C3F1/N
      mice. In these studies, a treatment-related macrocytic regenerative anemia
      characterized by increased levels of methemoglobin and Heinz body formation
      developed within a few weeks of DMPT exposure in rats and mice. DMPT induced
      nasal cavity, splenic, and liver toxicity in rats and mice at 3 months and 2
      years. DMPT carcinogenic effects were seen in the liver of male and female rats
      and mice, the nasal cavity of male and female rats, and the lung and forestomach
      of female mice. In rodents, DMPT is distributed to many of the sites where toxic
      and carcinogenic effects occurred. DMPT-induced oxidative damage at these target
      sites may be one mechanism for the treatment-related lesions. Methemoglobinemia,
      as seen in these DMPT studies, is caused by oxidation of the heme moiety, and
      this end point served as an early alert for other target organ toxicities and
      carcinogenic responses that followed with longer term exposure. 

PMID- 23867144
TI  - Brief communication: intraperitoneal galactosamine misdosing as a possible
      interpretation for responder/nonresponder phenotypes.
AB  - Previous reports investigating the mechanisms of galactosamine toxicity have
      discussed the presence of responders and nonresponders after intraperitoneal (IP)
      administration of a toxic dose. The incidence of nonresponders has been reported
      to be as high as 47%. To rule out inadvertent intestinal, solid organ, or
      subcutaneous injection as at least a partial cause for the variability, we
      performed midline incisions and dosed 10 rats via a flexible catheter, with a
      toxic dose of galactosamine. Results were compared to a previous range finding
      study with IP-injected rats. As opposed to the IP-injected rats that had a
      roughly 50% response rate (based on serum alanine aminotransferase [ALT]
      elevation) and 100% of the midline incision catheter-instilled rats had
      elevations in ALT. Saline controls had no elevations. Histopathologic examination
      of livers from 5 midline-incisioned rats euthanized 48 hr after dosing with the
      lowest ALT responses revealed portal eosinophilic infiltrates and biliary
      hypertrophy/hyperplasia contiguous with areas of necrosis. Examination of 5 rats
      with the highest ALT elevations euthanized 10 days post dose revealed similar
      lesions to be resolving. We conclude that a significant contribution to
      variability in response to IP-injected galactosamine and possibly other
      investigative drugs is inadvertent misinjection of all or part of the dose. 

PMID- 23867145
TI  - Trends in community violence in England and Wales 2005-2009.
AB  - PURPOSE: Injury records from Emergency Departments (EDs) have been studied over
      the last decade as part of the work of the National Violence Surveillance Network
      (NVSN) and provide information about local, regional and national violence levels
      and trends in England and Wales. The purpose of the current study is to evaluate
      overall, gender, age-specific and regional trends in community violence in
      England and Wales from an ED perspective from January 2005 to December 2009.
      METHODS: Violence-related injury data were collected prospectively in a
      stratified sample of 77 EDs (Types 1, 3 and 4) in the nine Government Office
      Regions in England and in Wales. All 77 EDs were recruited on the basis that they
      had implemented and continued to comply with the provisions of the 1998 Data
      Protection Act and Caldicott guidance. Attendance date, age and gender of
      patients who reported injury in violence were identified using assault-related
      attendance codes, specified at the local level. Time series statistical methods
      were used to detect both regional and national trends. RESULTS: In total 221,673
      (163,384 males: 74%) violence-related attendances were identified. Overall
      estimated annual injury rate was 6.5 per 1000 resident population (males 9.8 and
      females 3.4 per 1000). Violence affecting males and females decreased
      significantly in England and Wales over the 5-year period, with an overall
      estimated annual decrease of 3% (95% CI: 1.8-4.1%, p<0.05). Attendances decreased
      significantly for both genders across four out of the five age groups studied.
      Attendances were found to be highest during the months of May and July and lowest
      in February. Substantial differences in violence-related ED attendances were
      identified at the regional level. CONCLUSIONS: From this ED perspective overall
      violence in England and Wales decreased over the period 2005-2009 but increased
      in East Midlands, London and South West regions. Since 2006, overall trends
      according to Crime Survey for England and Wales (CSEW), police and ED measures
      were similar, though CSEW and ED measures reflect far greater numbers of violent
      incidents than police data. Causes of decreases in violence in regions need to be
      identified and shared with regions where violence increased.

PMID- 23867146
TI  - Elimination of non-pulmonary vein ectopy by ethanol infusion in the vein of
      Marshall.

PMID- 23867147
TI  - Mitochondria-derived organelles in the diplomonad fish parasite Spironucleus
      vortens.
AB  - In some eukaryotes, mitochondria have become modified during evolution to yield
      derived organelles (MDOs) of a similar size (hydrogenosomes), or extremely
      reduced to produce tiny cellular vesicles (mitosomes). The current study provides
      evidence for the presence of MDOs in the highly infectious fish pathogen
      Spironucleus vortens, an organism that produces H2 and is shown here to have no
      detectable cytochromes. Transmission electron microscopy (TEM) reveals that S.
      vortens trophozoites contain electron-dense, membranous structures sometimes with
      an electron-dense core (200 nm-1 MUm), resembling the hydrogenosomes previously
      described in other protists from habitats deficient in O2. Confocal microscopy
      establishes that these organelles exhibit autofluorescence emission spectra
      similar to flavoprotein constituents previously described for mitochondria and
      also present in hydrogenosomes. These organelles possess a membrane potential and
      are labelled by a fluorescently labeled antibody against Fe-hydrogenase from
      Blastocystis hominis. Heterologous antibodies raised to mitochondrial proteins
      frataxin and Isu1, also exhibit a discrete punctate pattern of localization in S.
      vortens; however these labelled structures are distinctly smaller (90-150 nm)
      than hydrogenosomes as observed previously in other organisms. TEM confirms the
      presence of double-membrane bounded organelles of this smaller size. In addition,
      strong background immunostaining occurs in the cytosol for frataxin and Isu1, and
      labelling by anti-ferredoxin antibody is generally distributed and not
      specifically localized except for at the anterior polar region. This suggests
      that some of the functions traditionally attributed to such MDOs may also occur
      elsewhere. The specialized parasitic life-style of S. vortens may necessitate
      more complex intracellular compartmentation of redox reactions than previously
      recognized. Control of infection requires biochemical characterization of redox
      related organelles.

PMID- 23867148
TI  - Description of three new species of Hepatozoon (Apicomplexa, Hepatozoidae) from
      Rattlesnakes (Crotalus durissus terrificus) based on molecular, morphometric and
      morphologic characters.
AB  - Hepatozoon spp. are commonly found infecting snakes. Since the latter are
      parasitized by diverse forms and data in the literature show divergence, we
      studied Hepatozoon spp. diversity on Crotalus durissus terrificus snakes using
      both molecular and morphological approaches. Naturally infected animals were
      employed. Blood was collected, blood smears were prepared and an aliquot was
      stored at -20 degrees C for DNA extraction. Five specimens of C. durissus
      terrificus were selected, each of them infected with one gamont type.
      Morphological and morphometric analyses of the found gamonts led to their
      grouping into three populations. For molecular characterization, seven
      oligonucleotide pairs that amplify distinct regions of rDNA gene were tested by
      adopting the PCR technique. Only the oligonucleotide pairs HepF300/Hep900 and
      HEMO1/HEMO2 were efficient in amplifying and distinguishing different isolates of
      Hepatozoon spp. from snakes. The better results were obtained when both
      oligonucleotide pairs were used in association. Based on the molecular and
      morphologic differences, three new species were proposed: Hepatozoon cuestensis
      sp. nov.; Hepatozoon cevapii sp. nov. and Hepatozoon massardii sp. nov. This is
      the first description of new Hepatozoon species from snakes, based on molecular
      characterization and morphological data, in South America. 

PMID- 23867149
TI  - The prototypical histamine H3 receptor inverse agonist thioperamide improves
      multiple aspects of memory processing in an inhibitory avoidance task.
AB  - Numerous studies have found that histamine plays a major role in memory and that
      the histamine H3 receptor (H3R) inverse agonist thioperamide improves cognitive
      performance in various animal models. However, little is known about the stages
      of memory that are specifically affected by thioperamide. The purpose of the
      present study was to investigate the effects of thioperamide on acquisition,
      consolidation and retrieval processes in a one-trial inhibitory avoidance task in
      female C57BL/6J mice. In addition, potential state-dependency effects were
      studied by injecting thioperamide before the training and the test sessions in
      order to induce similar physiological states during acquisition and retrieval.
      Our results indicate that post-training systemic administration of thioperamide
      facilitated consolidation. Moreover, the administration of thioperamide before
      the training session had no effect on latency to enter the black compartment
      during training but enhanced memory during the retention test. The administration
      of thioperamide before the retention test also increased performance, which
      indicates that this compound ameliorates memory retrieval. Finally, when animals
      received thioperamide before the training session and before the retention test,
      the cognitive enhancing effects of thioperamide were not significantly changed.
      Together, our results show that thioperamide improves cognitive performance in an
      inhibitory avoidance task through actions on different memory stages.
      Furthermore, inducing a similar physiological state with thioperamide during
      acquisition and retrieval do not significantly affect cognitive enhancement. Our
      results suggest that the blockade of H3R can be helpful for the treatment of
      neuropsychiatric conditions characterized by deficits affecting several stages of
      memory processing. 

PMID- 23867150
TI  - Evaluation of spontaneous recovery of behavioral and brain injury profiles in
      zebrafish after hypoxia.
AB  - Cerebral hypoxia-ischemia can lead to motor and sensory impairments which can be
      dependent on the extent of infarcted regions. Since a better understanding of the
      neurochemical mechanisms involved in this injury is needed, the use of zebrafish
      as a cerebral hypoxia model has become quite promising because it could improve
      the knowledge about hypoxia-ischemia. In the current study, we aimed to
      investigate the spontaneous recovery of brain and behavioral impairments induced
      by hypoxia in adult zebrafish. Brain injury levels were analyzed by
      spectrophotometric measurement of mitochondrial dehydrogenase activity by
      staining with 2,3,5-triphenyltetrazolium chloride, and behavioral profiles were
      assessed by the open tank test. The induction of hypoxia substantially decreased
      mitochondrial activity in the brain and impaired behavior. The spontaneous
      recovery of fish subjected to hypoxia was assessed after 1, 3, 6, 24, and 48h
      under normoxia. The quantification of brain injury levels showed a significant
      increase until 24h after hypoxia, but after 48h this effect was completely
      reversed. Regarding behavioral parameters, we verified that locomotor activity
      and vertical exploration were impaired by hypoxia and these effects were reversed
      after 3h under normoxia. Taken together, these results show that zebrafish
      exhibited transient cerebral and behavioral impairments when submitted to
      hypoxia, and 1h under normoxic conditions was insufficient to reverse both
      effects. Therefore, our data help to elucidate the time window of spontaneous
      recovery in zebrafish after hypoxia and also the behavioral phenotypes involved
      in this phenomenon. 

PMID- 23867151
TI  - Gradual electroforming and memristive switching in Pt/CuO(x)/Si/Pt systems.
AB  - We report a memristive switching effect in Pt/CuOx/Si/Pt devices prepared by the
      rf sputtering technique at room temperature. Differently from other Cu-based
      metal filament switching systems, a gradual electroforming process, marked by a
      gradual increase of the device resistance and a gradual decrease of the device
      capacitance, was observed in the current-voltage and capacitance characteristics.
      After the gradual electroforming, the devices show a uniform memristive switching
      behavior. By Auger electron spectroscopy analysis, a model based on the thickness
      change of the SiOx layer at the CuOx/Si interface and Cu ion migration is
      proposed for the gradual electroforming and uniform memristive switching,
      respectively. This work should be meaningful for the preparation of forming-free
      and homogeneous memristive devices. 

PMID- 23867152
TI  - A randomized trial to consider the effect of Romanian deadlift exercise on the
      development of lumbar extension strength.
AB  - OBJECTIVE: To consider the efficacy of 10 weeks of Romanian deadlift (DL)
      training in increasing lumbar extension strength compared to isolated lumbar
      extension (LUMX) training. DESIGN: Comparison of pre- and post-test data for
      Romanian deadlift 1RM, and lumbar extension torque between and within groups.
      PARTICIPANTS: Male trained subjects (n = 36; (x-+/-SD) 24.9 +/- 6.5 years; 178.5
      +/- 5.2 cm; 81.6 +/- 10.0 kg). MAIN OUTCOME MEASURES: Pre- and post-testing
      included a Romanian deadlift 1RM and isometric strength tests every 12 degrees 
      through full range of motion on the MedX lumbar extension machine (MedX, Ocala,
      FL). RESULTS: Repeated measures analysis of variance (ANOVA) with Bonferroni
      adjustments revealed that 1RM Romanian deadlift significantly increased from pre-
      to post-test in the DL group (p < 0.008; 143.3 +/- 23.4 kg to 166.3 +/- 21.9 kg)
      and the LUMX group (p < 0.008; 135.8 +/- 23.1 kg to 146.0 +/- 25.5 kg). In
      contrast, tested functional torque (TFT) significantly increased at 6 out of 7
      joint angles (p < 0.008) for the LUMX group only. The control group showed no
      significant differences pre- to post-test. CONCLUSIONS: These data suggest that
      the Romanian deadlift does not enhance lumbar extension torque. However,
      performing specific isolated lumbar extension training appears to improve both
      lumbar extension torque and Romanian deadlift 1RM.

PMID- 23867153
TI  - Junior Australian football injury research: are we moving forward?
AB  - Summarise the progress of junior Australian football (AF) injury research in line
      with the six stages of the 'Translating Research into Injury Prevention Practice'
      (TRIPP) model, in order to direct future research for the area. Systematically
      searched narrative review. Bibliographic research databases (Medline, PubMed,
      Scopus, and SPORTDiscusTM) were used to search for original studies in which
      injuries in junior AF players were investigated. 18 studies (NHMRC levels of
      evidence ranging from NHMRC II-IV) addressed junior AF injuries within the TRIPP
      model. Injury surveillance (stage 1) was represented by five studies, aetiology
      and mechanism of injury (stage 2) was represented by various contributions from
      12 studies, and injury prevention (stages 3-6) was represented by five papers.
      All papers addressing TRIPP stage 1 suffered from methodological discrepancies
      and inconsistencies in the data that are reported. Hence, a consistent injury
      definition and ongoing injury surveillance remains a priority. Injury research at
      the junior level of AF is predominantly situated at stage 2 of the TRIPP process.
      It can be postulated that most junior AF injury prevention programs are based
      upon senior AF research and anecdotal evidence due to the paucity of studies
      addressing stages 3-6. 

PMID- 23867155
TI  - Introduction to serial reviews on selenium and diabetes type 2--an unexpected
      link.

PMID- 23867154
TI  - Selenium and diabetes--evidence from animal studies.
AB  - Whereas selenium was found to act as an insulin mimic and to be antidiabetic in
      earlier studies, recent animal experiments and human trials have shown an
      unexpected risk of prolonged high Se intake in potentiating insulin resistance
      and type 2 diabetes. Elevating dietary Se intake (0.4 to 3.0mg/kg of diet) above
      the nutrient requirements, similar to overproduction of selenoproteins, led to
      insulin resistance and/or diabetes-like phenotypes in mice, rats, and pigs.
      Although its diabetogenic mechanism remains unclear, high Se intake elevated
      activity or production of selenoproteins including GPx1, MsrB1, SelS, and SelP.
      This upregulation diminished intracellular reactive oxygen species and then
      dysregulated key regulators of beta cells and insulin synthesis and secretion,
      leading to chronic hyperinsulinemia. Overscavenging intracellular H2O2 also
      attenuated oxidative inhibition of protein tyrosine phosphatases and suppressed
      insulin signaling. High Se intake might affect expression and/or function of key
      regulators of glycolysis, gluconeogenesis, and lipogenesis. Future research is
      needed to find out if certain forms of Se metabolites in addition to
      selenoproteins and if mechanisms other than intracellular redox control mediate
      the diabetogenic effects of high Se intake. Furthermore, a potential interactive
      role of high Se intake in the interphase of carcinogenesis and diabetogenesis
      should be explored to make optimal use of Se in human nutrition and health. 

PMID- 23867156
TI  - miR-761 regulates the mitochondrial network by targeting mitochondrial fission
      factor.
AB  - Mitochondria are dynamic organelles that constantly undergo fission and fusion.
      The balance between fission and fusion determines the fate of the cell. In this
      study, we show that mitochondrial fission factor (MFF) is upregulated upon
      hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Knockdown of
      MFF attenuated hydrogen peroxide- and I/R injury-induced cardiomyocyte apoptosis
      and myocardial infarction. We found that MFF is a direct target of miR-761, and
      miR-761 inhibits mitochondrial fission and cardiomyocyte apoptosis by repressing
      MFF. This study reveals a novel model of mitochondrial fission regulation, which
      is composed of miR-761 and MFF. Modulation of their levels may provide a new
      approach for tackling apoptosis and myocardial infarction. 

PMID- 23867157
TI  - Accurate measurement of nitrate, nitrite, and S-nitrosothiols in biological
      samples by mass spectrometry.

PMID- 23867158
TI  - A randomized pilot trial of dietary modification for the chemoprevention of
      noninvasive bladder cancer: the dietary intervention in bladder cancer study.
AB  - Epidemiological data suggest robust associations of high vegetable intake with
      decreased risks of bladder cancer incidence and mortality, but translational
      prevention studies have yet to be conducted. We designed and tested a novel
      intervention to increase vegetable intake in patients with noninvasive bladder
      cancer. We randomized 48 patients aged 50 to 80 years with biopsy-proven
      noninvasive (Ta, T1, or carcinoma in situ) urothelial cell carcinoma to telephone
      and Skype-based dietary counseling or a control condition that provided print
      materials only. The intervention behavioral goals promoted seven daily vegetable
      servings, with at least two of these as cruciferous vegetables. Outcome variables
      were self-reported diet and plasma carotenoid and 24-hour urinary isothiocyanate
      (ITC) concentrations. We used two-sample t tests to assess between-group
      differences at 6-month follow-up. After 6 months, intervention patients had
      higher daily intakes of vegetable juice (P = 0.02), total vegetables (P = 0.02),
      and cruciferous vegetables (P = 0.07); lower daily intakes of energy (P = 0.007),
      fat (P = 0.002) and energy from fat (P = 0.06); and higher plasma alpha-carotene
      concentrations (P = 0.03). Self-reported cruciferous vegetable intake correlated
      with urinary ITC concentrations at baseline (P < 0.001) and at 6 months (P =
      0.03). Although urinary ITC concentrations increased in the intervention group
      and decreased in the control group, these changes did not attain between-group
      significance (P = 0.32). In patients with noninvasive bladder cancer, our novel
      intervention induced diet changes associated with protective effects against
      bladder cancer. These data show the feasibility of implementing therapeutic
      dietary modifications to prevent recurrent and progressive bladder cancer.

PMID- 23867159
TI  - Analysis of the Sherlock II tip location system for inserting peripherally
      inserted central venous catheters.
AB  - Peripherally inserted central catheters (PICCs) are frequently placed at the
      bedside. The purpose of our study was to evaluate the efficacy of the Sherlock II
      tip location system (Bard Access Systems, Salt Lake City, UT), which offers
      electromagnetic detection of the PICC tip to assist the operator in guiding the
      tip to a desired location. We performed a retrospective review of patients who
      had a bedside PICC using the Sherlock II tip location system. Three hundred
      seventy-five of 384 patients (97.7%) had the catheter tip positioned
      appropriately. Our results suggest that the Sherlock II tip location system is an
      efficacious system for bedside PICC placement. 

PMID- 23867160
TI  - Aneurysmal bone cyst of the zygomatic arch: a case report.
AB  - We describe a case of an aneurysmal bone cyst originating from the zygomatic
      arch, which, according to the literature, is an extremely rare location. In the
      preoperative diagnosis the characteristic radiological signs of the high-quality
      computed tomography and magnetic resonance examinations were the cornerstones.
      Treatment was successful total excision. Careful diagnostic workup and
      multidisciplinary approach (head and neck surgeon, radiologist, and pathologist)
      should be utilized to successfully diagnose and to treat this rare pathology. 

PMID- 23867161
TI  - Daintain/AIF-1 plays roles in coronary heart disease via affecting the blood
      composition and promoting macrophage uptake and foam cell formation.
AB  - BACKGROUND: Daintain/AIF-1 is an inflammatory polypeptide factor/allograft
      inflammatory factor 1 derived from macrophages. It is characterized in APOE(-/-)
      mice as a novel inflammatory factor associated with atherosclerosis. The purpose
      of this study was to characterize its function in human atherosclerosis. METHODS:
      Immunohistochemistry was used to identify the expression of daintain/AIF-1 in
      vessel segments within and far from atherosclerotic plaques; High-performance
      liquid chromatography (HPLC) was used to display the effects of daintain/AIF-1 on
      C-reactive protein (CRP), oxidative capacity and superoxide dismutase (SOD) in
      vivo; Oil Red O Staining was used to show the effects of daintain/AIF-1 on uptake
      of oxidized low density lipoprotein (ox-LDL) into U937 cells, a macrophage line;
      Western Blot was used to test scavenger receptor A (SRA) expression. RESULTS: A
      high density of daintain/AIF-1 was observed in the tunica intima and media of
      coronary artery with atherosclerotic plaque, and fewer daintain/AIF-1 in the
      vessels without atherosclerotic plaque; Daintain/AIF-1 injected intravenously
      into BALB/c mice boosted oxidative capacity, significantly impaired SOD
      activities and augmented the CRP level in blood. According to the oil red O test,
      daintain/AIF-1 profoundly facilitated the uptake of ox-LDL in U937 macrophages
      and formation of foam cells in the endothelium. We also found that the molecular
      mechanisms are effective by promoting overexpression of SRA on macrophages.
      CONCLUSION: These findings implicate that the inflammatory factor daintain/AIF-1
      is closely associated with atherogenesis, and could be further characterized as a
      novel risk factor for atherosclerosis.

PMID- 23867162
TI  - Thermal and endocrine regulation of gonadal apoptosis during sex differentiation
      in pejerrey Odontesthes bonariensis.
AB  - The fate of the differentiating gonads in pejerrey Odontesthes bonariensis is
      determined by the environmental water temperature experienced by the larvae
      during the critical period of sex determination. We previously reported a link
      between apoptosis, temperature and sex differentiation in this species. To
      clarify this link, we subjected larvae to thermal and endocrine treatments
      between hatching and the onset of histological sex differentiation of the gonads
      and assessed the patterns of gonadal development and apoptosis by light
      microscopic histology and terminal deoxynucleotidyl transferase-mediated dUTP
      nick end labeling (TUNEL) analysis, respectively. Apoptotic labeling was
      widespread among somatic cells of the anterior region of the right gonads of fish
      reared at the male-producing temperature (MPT) and part of the fish at the mixed
      sex-producing temperature prior to sex differentiation. In contrast, TUNEL
      positive cells were rarely observed in gonads at the female-producing temperature
      (FPT). Administration of exogenous estrogen completely prevented MPT-induced
      masculinization, induced feminization and reduced gonadal apoptosis, whereas an
      aromatase inhibitor (fadrozole) induced TUNEL signals in the gonads of FPT-reared
      larvae. These results provide strong evidence that apoptosis in somatic cells in
      the right lobe of the gonads might play a key role in testicular differentiation
      in pejerrey and that estrogens are involved in the regulation of this process.

PMID- 23867163
TI  - Biologic properties of gadolinium diethylenetriaminepentaacetic acid-labeled and
      PKH26-labeled human umbilical cord mesenchymal stromal cells.
AB  - BACKGROUND AIMS: This study was conducted to characterize gadolinium
      diethylenetriaminepentaacetic acid (Gd-DTPA)-labeled and PKH26-labeled human
      umbilical cord mesenchymal stromal cells (HuMSCs) and to track them with magnetic
      resonance imaging (MRI) in vitro and in vivo. METHODS: HuMSCs were isolated from
      umbilical cords and expanded in vitro. Cells were sequentially labeled with Gd
      DTPA and PKH26. The labeling efficiency was determined by spectrophotometry
      measurements, and the longevity of Gd-DTPA maintenance was measured with MRI. The
      influence of double labeling on cellular biologic properties was assessed by cell
      proliferation, viability, differentiation, cycle and apoptosis. Transplantation
      of double-labeled HuMSCs or placebo was performed in 39 female Sprague-Dawley
      rats. Leak point pressure and maximal bladder capacity were measured in animals 6
      weeks after injection. RESULTS: The T1 values and signal intensity on T1-weighted
      imaging of labeled cells were significantly higher than the control group (P <
      0.05). The signal intensity on T1-weighted imaging of labeled cells was retained
      >14 days in vitro and in vivo. There was no significant difference in the cell
      cycle, cell apoptosis, cell proliferation and cell viability between labeled and
      unlabeled HuMSCs (P > 0.05). After double labeling, HuMSCs were still capable of
      differentiating into osteoblasts and adipocytes. Periurethrally injected HuMSCs
      in the rats significantly improved leak point pressure and maximal bladder
      capacity. CONCLUSIONS: HuMSCs were successfully labeled with Gd-DTPA and PKH26.
      This labeling method is reliable and efficient and can be applied for tracking
      cells in vitro and in vivo without altering cellular biologic properties.

PMID- 23867164
TI  - Identification of GNE-293, a potent and selective PI3Kdelta inhibitor: navigating
      in vitro genotoxicity while improving potency and selectivity.
AB  - In an effort to identify potent and isoform selective inhibitors of PI3Kdelta,
      GNE-293 (34) was identified. Inhibitor 2 was found to induce micronuclei
      formation in both the MNT and HCA in vitro assays. Compounds testing negative for
      genotoxicity were successfully identified through modifications of the 2
      benzimidazole substituent and the methylene moiety to disrupt planarity. A
      variety of heteroatom linkers were explored to examine their effect on potency
      and isoform selectivity by restricting torsional angles to favor ligand
      interactions with PI3Kdelta's Trp760. These modifications also resulted in an
      improved in vivo pharmacokinetic profile. 

PMID- 23867165
TI  - Exploration of the 5-bromopyrimidin-4(3H)-ones as potent inhibitors of PDE5.
AB  - The substituents both at the 6-position of the 5-bromopyrimidinone ring and at
      the 5'-position of the phenyl ring of 5-bromopyrimidin-4(3H)-ones were explored.
      5-Bromo-6-isopropyl-2-(2-propoxy-phenyl)pyrimidin-4(3H)-one was identified as a
      new scaffold for potent PDE5 inhibitors. The crystal structures of PDE5/2e and
      PDE5/10a complexes provided a structural basis for the inhibition of 5
      bromopyrimidinones to PDE5. In addition, it was also found that there is a great
      tolerance for the substitution at the 5'-position of the phenyl ring of 5
      bormopyrimidinones and the resulted compound 13a has the highest inhibition
      activity to PDE5 (IC50, 1.7 nM).

PMID- 23867166
TI  - Synthesis and structure activity relationship of imidazo[1,2-a]pyridine-8
      carboxamides as a novel antimycobacterial lead series.
AB  - Imidazo[1,2-a]pyridine-8-carboxamides as a novel antimycobacterial lead were
      generated by whole cell screening of a focused library against Mycobacterium
      tuberculosis. Herein, we describe the synthesis and structure activity
      relationship evaluation of this class of inhibitors and the optimization of
      physicochemical properties. These are selective inhibitors of Mycobacterium
      tuberculosis with no activity on either gram positive or gram negative pathogens.

PMID- 23867167
TI  - Syntheses of procyanidin B2 and B3 gallate derivatives using equimolar
      condensation mediated by Yb(OTf)3 and their antitumor activities.
AB  - Synthesis of procyanidin B2 and B3 gallate derivatives, 3-O-gallate, 3"-O
      gallate, and 3,3"-di-O-gallate, were synthesized using equimolar condensation
      mediated by Yb(OTf)3. Synthesized compounds showed significant antitumor effects
      against human prostate PC-3 cell lines. Their activities were weaker than well
      known EGCG and prodelphinidin B3.

PMID- 23867168
TI  - Structure activity relationship study of benzo[d]thiazol-2(3H)one based sigma
      receptor ligands.
AB  - Herein we report the SAR study which involved structural modifications to the
      linker length, aryl substitution and alkylamine ring size of the benzo[d]thiazol
      2(3H)one based sigma receptor (sigma) ligands. Many compounds in this series
      displayed low nanomolar affinity for the sigma receptor subtypes. In particular,
      8a showed high affinity (sigma-1 Ki = 4.5 nM) for sigma-1 receptors and
      moderately high selectivity (483-fold) over sigma-2 receptors.

PMID- 23867169
TI  - Medial scapular muscle detachment: clinical presentation and surgical treatment.
AB  - BACKGROUND: This study describes the clinical presentation and preliminary
      outcomes in a cohort of patients treated for detachment of the medial scapular
      stabilizing muscles. METHODS AND METHODS: The study included 72 patients who
      underwent reattachment of the lower trapezius and rhomboid muscles. Patients
      presented with a history of a high level of medial scapular border pain during
      activity and inability to perform overhead or forward flexion activities.
      Clinical examination demonstrated palpable tenderness along the medial scapular
      border, palpable defect along the medial border muscles, scapular dyskinesis,
      decreased scapular/rotator cuff strength, and modification of symptoms by manual
      scapular repositioning. Surgical exploration revealed detachment of the lower
      trapezius muscle or rhomboid muscles, requiring muscle reattachment to the
      scapula. Clinical outcomes were measured by the American Shoulder and Elbow
      Surgeons (ASES) self-report form, with comparisons made between the overall
      scores and subcomponents obtained at initial evaluation, discharge from active
      care, and postdischarge follow-up. RESULTS: Time from injury to treatment
      averaged 52 months, and time from surgery to discharge was 7.4 months. ASES
      scores significantly improved from initial evaluation (39 +/- 16) to discharge
      (63 +/- 21) (P < .001). At medium-term follow-up (n = 23), ASES scores
      significantly improved from initial evaluation (38 +/- 14) to discharge (69 +/-
      20) (P < .001). CONCLUSIONS: Scapular muscle detachment appears to be a
      clinically identifiable syndrome with a homogeneous set of history and physical
      findings. Surgical treatment can significantly reduce pain and improve functional
      outcomes.

PMID- 23867170
TI  - The association between peritoneal charge barrier dysfunction and protein lost
      during continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND/AIMS: The main purpose of the present study was to determine the
      effect of peritoneal charge barrier dysfunction on hypoalbuminemia during CAPD.
      METHODS: We measured the association of dialysis dose, peritoneal equilibration
      test (PET) results (ratio of dialysate and plasma creatinine), and peritoneal
      charge barrier index (ratio of pancreatic and salivary alpha-amylase clearance)
      on protein loss in 33 patients on maintenance CAPD. All patients were from a
      single institution and were diagnosed with chronic nephritis (n = 18 cases),
      diabetic nephropathy (n = 8), hypertension (n = 5), and hepatitis B virus
      associated glomerulonephritis (n = 2). RESULTS: The mean (+/- SD) dialysate
      protein loss was 4.04 g (+/- 1.97) per day. Protein loss was positively
      correlated with dialysis dose (r = 0.438, p = 0.01) but was not significantly
      correlated with PET results. The mean (+/- SD) peritoneal charge barrier index
      was 6.12 (+/- 21.20) and was inversely correlated with protein loss into the
      peritoneal dialysate (r = -0.532, p < 0.01). CONCLUSIONS: Taken together, our
      study of CAPD patients indicates that protein loss into the peritoneal dialysate
      increases with peritoneal dialysis dose and with disruption of the peritoneal
      charge barrier. (c) 2013 S. Karger AG, Basel.

PMID- 23867171
TI  - Expression pattern of vascular endothelial growth factor 2 during sea urchin
      development.
AB  - The VEGF family in the sea urchin is comprised of three members designated Vegf1
      through Vegf3. In this study, we found a high level of similarity between the
      PDGF/VEGF domain of the predicted gene Sp-Vegf2 in the sea urchin
      Strongylocentrotus purpuratus and the same domain of a gene that we found in a
      closely related sea urchin, Strongylocentrotus intermedius. The sequence of the
      Si-Vegf2 cDNA was determined, and the expression of the Si-Vegf2 mRNA throughout
      early sea urchin development was studied by RT-PCR and in situ hybridization.
      Also we analyzed phylogenetic relationships of Si-Vegf2 and other members of the
      PDGF and VEGF families. We have found that the Si-Vegf2 present during the time
      span from the egg to the 4-arm pluteus stage. This mRNA is uniformly distributed
      in eggs, cleaving embryos and early blastulae. At the gastrula stage, the Si
      Vegf2 transcripts are localized in the ventrolateral clusters of primary
      mesenchyme cells, and later, at the prism stage, they are detected in the forming
      apex. At the early pluteus stage, Si-Vegf2 mRNAs are found in two groups of
      mesenchyme cells in the scheitel region on the apical pole. We have determined
      that Si-Vegf2 is a mesenchyme-expressed factor but its developmental function is
      unknown. 

PMID- 23867172
TI  - Radiocarpal and first metatarsophalangeal intraarticular injection site
      confirmation with fluoroscopy and review of accuracy of intraarticular
      injections.
AB  - The aim of this study was to determine the accuracy of radiocarpal (RC) joint and
      first metatarsophalangeal (MTP) joint arthrocentesis using fluoroscopy.
      Rheumatologists were asked to mark their usual site of arthrocentesis over
      fluoroscopically identified joint lines of the right RC and right first MTP
      joints. Ten rheumatologists with a mean of 17.9 years of clinical experience
      participated. The sites marked were a mean of 0.85 cm (range, 0-1.6 cm; SD, 0.5
      cm) and 0.33 cm (range, 0-1.3 cm; SD, 0.4 cm) from the fluoroscopically
      identified RC and MTP joints, respectively. Traditional palpation-guided joint
      aspiration may be inaccurate. Fluoroscopic guidance has the potential to improve
      accuracy of arthrocentesis of small joints.

PMID- 23867173
TI  - Risk factors for complications in donors at first and repeat whole blood
      donation: a cohort study with assessment of the impact on donor return.
AB  - BACKGROUND: First-time donation is among recognised risk factors for vasovagal
      reactions to blood donation and reactions are known to reduce donor return. We
      assessed associations between potential risk factors and vasovagal reactions and
      needle-related complications in first-time whole blood donation in comparison to
      repeat donation and analysed the impact of complications on donor return.
      MATERIALS AND METHODS: We performed a cohort study on whole blood donations in
      The Netherlands from 1/1/2010 to 31/12/2010 using data extracted from the blood
      service information system. Donation data up to 31/12/2011 were used to ascertain
      donor return. RESULTS: In 2010 28,786 donors made first whole blood donations and
      there were 522,958 repeat donations. Vasovagal reactions occurred in 3.9% of
      first donations by males and 3.5% of first donations by females compared to in
      0.2% and 0.6%, respectively, of repeat donations. Associations of vasovagal
      reactions with other factors including age, body weight, systolic and diastolic
      blood pressure were similar in first-time and repeat donors. Needle-related
      complications occurred in 0.2% of male and 0.5% of female first-time donations
      and in 0.1% and 0.3%, respectively, of repeat donations. Among first-time donors,
      the return rate within 1 year was 82% following an uncomplicated first donation,
      but 55% and 61% following vasovagal reactions and needle-related complications,
      respectively; the corresponding percentages among repeat donors were 86%, 58% and
      82%. DISCUSSION: Among first-time donors, females suffered less than males from
      vasovagal reactions. Other risk factors had similar associations among first-time
      and repeat donors. Vasovagal reactions and needle-related complications in both
      first-time and repeat donors are followed by reduced donor return.

PMID- 23867174
TI  - In reply to: "Further comments on platelet proteomics in Transfusion Medicine".

PMID- 23867175
TI  - Further comments on platelet proteomics in Transfusion Medicine.

PMID- 23867176
TI  - In reply: Post-transplant reactivation of Chagas disease in Italy.

PMID- 23867177
TI  - Reactivation of Chagas disease after a bone marrow transplant.

PMID- 23867178
TI  - Changing blood donor screening criteria from permanent deferral for men who have
      sex with men to individual sexual risk assessment: no evidence of a significant
      impact on the human immunodeficiency virus epidemic in Italy.
AB  - BACKGROUND: In 2001, the criteria for blood donor eligibility in Italy were
      modified by a ministerial decree from a permanent deferral for "men who have sex
      with men" to an individual risk assessment of sexual behaviours. The aim of this
      study was to evaluate the impact of this change in donor screening criteria on
      the human immunodeficiency virus epidemic among blood donors in Italy. MATERIALS
      AND METHODS: We used the data obtained from the Italian blood donor
      epidemiological surveillance system. We compared data collected in 2009 and 2010,
      when the individual risk assessment policy was applied, with data collected in
      1999 when permanent deferral was applied for men who have sex with men based on a
      declaration of sexual orientation. We evaluated the change over time in the
      relative proportion of HIV antibody-positive donors who likely acquired the
      infection from men who have sex with men vs heterosexual sexual exposure; the
      relative risk was calculated using 1999 as the reference year. RESULTS: In all 3
      years, the majority of HIV antibody-positive donors reported sexual exposure as a
      risk factor for HIV infection; this proportion increased over time, although not
      statistically significantly. Heterosexuals always accounted for at least 40% of
      all HIV antibody-positive cases. The rate of HIV antibody-positive donors
      increased similarly in men who have sex with men and heterosexuals; specifically,
      the rate of HIV antibody-positive cases per 100,000 donors was more than 2-fold
      higher among men who have sex with men in 2009-2010 than in 1999 (2009-2010 vs
      1999, RR =2.8; P =0.06), and that among heterosexuals was 1.5 fold higher (P
      =0.18). DISCUSSION: When comparing the period before (1999) and after (2009
      2010), the implementation of the individual risk assessment policy in 2001, no
      significant increase in the proportion of men who have sex with men compared to
      heterosexuals was observed among HIV antibody-positive blood donors, suggesting
      that the change in donor deferral policy did not lead to a disproportionate
      increase of HIV-seropositive men who have sex with men.

PMID- 23867179
TI  - Survey on the prevention and incidence of haemolytic disease of the newborn in
      Italy.
AB  - BACKGROUND: In 2010, the Italian Society of Immunohaematology and Transfusion
      Medicine (SIMTI) carried out a survey of the incidence of haemolytic disease of
      the newborn (HDN) and the prevention of HDN caused by anti-Rh(D) in Italian
      Transfusion Structures (TS). MATERIALS AND METHODS: A questionnaire divided into
      the following five sections was administered: (i) types of services provided and
      maintenance of legally required registers, (ii) immunoprophylaxis (IP), (iii) red
      cell typing and searches for irregular antibodies, (iv) evaluation of foetal
      maternal haemorrhage (FMH), and (v) incidence of HDN in 2010. Of the 280 TS sent
      the questionnaire, 176 (63%) replied. RESULTS: A HDN register was available in
      55.5% of the TS (n =91). Immunoprophylaxis with a dose of anti-D IgG was given to
      all Rh(D) negative and Rh(D) variant puerpera with Rh(D) positive newborns: in
      more than 93% of cases the dose was between 1,500 IU (300 MUg) and 1,250 IU (250
      MUg). Antenatal IP between the 25(th) and 28(th) week was proposed by 42 TS
      (26%). Seventy percent of the TS (n =115) did not make any evaluation of FMH. The
      number of births surveyed in 2010 was 203,384, the number of Rh(D) negative
      pregnancies was 13,569, while anti-D antibodies were present in 245 pregnancies.
      There were 111 cases of HDN due to anti Rh(D) incompatibility and in 40 of these,
      intrauterine transfusion (n =8) or exchange transfusion (n =32) was necessary. In
      94 cases HDN was due to other irregular antibodies: in 4 of these cases
      intrauterine transfusion was needed and in 11 other recourse was made of exchange
      transfusion. Finally, there were 1,456 newborns with ABO HDN of whom 13 underwent
      exchange transfusion. DISCUSSION: The data collected give a picture of the
      incidence of HDN in Italy and of the methods of managing IP and could form the
      basis for an update of the SIMTI recommendations on the management and prevention
      of this disease.

PMID- 23867180
TI  - Systematic RH genotyping and variant identification in French donors of African
      origin.
AB  - BACKGROUND: RH molecular analysis has enabled the documentation of numerous
      variants of RHD and RHCE alleles, especially in individuals of African origin.
      The aim of the present study was to determine the type and frequency of D and/or
      RhCE variants among blood donors of African origin in France, by performing a
      systematic RH molecular analysis, in order to evaluate the implications for blood
      transfusion of patients of African origin. MATERIALS AND METHODS: Samples from
      316 African blood donors, whose origin was established by their Fy(a-b-)
      phenotype, were first analysed using the RHD and RHCE BeadChips Kit (BioArray
      Solutions, Immucor, Warren, NJ, USA). Sequencing was performed when necessary.
      RESULTS: RHD molecular analysis showed that 26.2% of donors had a variant RHD
      allele. It allowed the prediction of a partial D in 11% of cases. RHCE molecular
      analysis showed that 14.2% of donors had a variant RHCE allele or RH [RN or
      (C)ces] haplotype. A rare Rh phenotype associated with the loss of a high
      prevalence antigen or partial RhCE antigens were predicted from RHCE molecular
      analysis in 1 (0.3%) and 17 (5%) cases, respectively. DISCUSSION: Systematic RHD
      and RHCE molecular analysis performed in blood donors of African origin provides
      transfusion-relevant information for individuals of African origin because of the
      frequency of variant RH alleles. RH molecular analysis may improve transfusion
      therapy of patients by allowing better donor and recipient matching, based not
      only on phenotypically matched red blood cell units, but also on units that are
      genetically matched with regards to RhCE variants.

PMID- 23867182
TI  - Experimental model for the study of the effects of platelet-rich plasma on the
      early phases of muscle healing.
AB  - BACKGROUND: There is abundant evidence suggesting that growth factors may play a
      key role in the healing process, especially in the early stages of inflammation.
      Despite the reported clinical successes with the use of growth factors there is
      still a lack of knowledge on the biological mechanism underlying the activity of
      platelet-rich plasma during the process of muscle healing. The aim of this study
      was to analyse the early effects of platelet- rich plasma in an easily
      reproducible animal model. MATERIALS AND METHODS: Wistar male adult rats (n=102)
      were used in this study. The muscle lesion was created with a scalpel in the
      flexor sublimis muscles. Platelet-rich plasma was applied immediately after
      surgery. Treated, untreated and contralateral muscles were analysed by
      morphological evaluation and western blot assay. RESULTS: Leucocyte infiltration
      was significantly greater in muscles treated with platelet-rich plasma than in
      both untreated and contralateral muscles. The latter showed greater leucocyte
      infiltration when compared to the untreated muscles. Platelet-rich plasma
      treatment also modified the cellular composition of the leucocyte infiltration
      leading to increased expression of CD3, CD8, CD19 and CD68 and to decreased CD4
      antigen expression in both platelet-rich plasma treated and contralateral
      muscles. Blood vessel density and blood vessel diameters were not statistically
      significantly different between the three groups analysed. DISCUSSION: The
      results of this study showed that treatment with platelet-rich plasma magnified
      the physiological early inflammatory response following a muscle injury,
      modifying the pattern of cellular recruitment. Local platelet-rich plasma
      treatment may exert a direct or, more plausibly, indirect systemic effect on
      healing processes, at least in the earliest inflammatory phase.

PMID- 23867183
TI  - Genotyping of human neutrophil antigens by polymerase chain reaction sequence
      based typing.
AB  - BACKGROUND: Genotyping for human neutrophil antigen (HNA) systems is required in
      the investigation of disorders involving alloimmunisation to HNA. We established
      a polymerase chain reaction sequence-based typing method for genotyping HNA and
      determined the genotype and allele frequencies of HNA in the Zhejiang Han
      population of China. MATERIALS AND METHODS: Four hundred, healthy unrelated
      Zhejiang Han individuals were recruited. Specific primers for HNA were designed
      and the polymerase chain reaction amplification conditions were optimised.
      Amplification amplicons were purified with enzyme digestion and then sequenced.
      RESULTS: The frequencies of the FCGR3B*01 and FCGR3B*02 alleles were 0.613 and
      0.387; no FCGR3B*03 allele was found. The frequencies of the SLC44A2*1 and
      SLC44A2*2 alleles were 0.654 and 0.346, respectively, while the frequencies of
      the ITGAL*1 (HNA-5a) and ITGAL*2 (HNA-5b) alleles were 0.896 and 0.104. Only
      ITGAM*1 (HNA-4a) allele was found in this study. Six single nucleotide
      polymorphisms were confirmed on sequenced regions separate from HNA
      polymorphisms, including FCGR3B (IVS3+39G>A and IVS3+52G>A), CD177(172A>G),
      SLC44A2 (IVS5-44A>G and IVS7-15T>C) and ITGAM (IVS3+118T>C). DISCUSSION: The
      polymerase chain reaction sequence-based typing method for genotyping HNA is
      reliable. These data of HNA alleles frequencies could contribute to the analysis
      of alloimmunisation to HNA in China.

PMID- 23867184
TI  - Adult and cord blood endothelial progenitor cells have different gene expression
      profiles and immunogenic potential.
AB  - BACKGROUND: Endothelial colony-forming cells (ECFC) are endowed with vascular
      regenerative ability in vivo and in vitro. In this study we compared the
      genotypic profile and the immunogenic potential of adult and cord blood ECFC, in
      order to explore the feasibility of using them as a cell therapy product.
      MATERIALS AND METHODS: ECFC were obtained from cord blood samples not suitable
      for haematopoietic stem cell transplantation and from adult healthy blood donors
      after informed consent. Genotypes were analysed by commercially available
      microarray assays and results were confirmed by real-time polymerase chain
      reaction analysis. HLA antigen expression was evaluated by flow-cytometry.
      Immunogenic capacity was investigated by evaluating the activation of allogeneic
      lymphocytes and monocytes in co-cultures with ECFC. RESULTS: Microarray assays
      revealed that the genetic profile of cord blood and adult ECFC differed in about
      20% of examined genes. We found that cord blood ECFC were characterised by lower
      pro-inflammatory and pro-thrombotic gene expression as compared to adult ECFC.
      Furthermore, whereas cord blood and adult ECFCs expressed similar amount of HLA
      molecules both at baseline and after incubation with gamma-interferon, cord blood
      ECFC elicited a weaker expression of pro-inflammatory cytokine genes. Finally, we
      observed no differences in the amount of HLA antigens expressed among cord blood
      ECFC, adult ECFC and mesenchymal cells. CONCLUSIONS: Our observations suggest
      that cord blood ECFC have a lower pro-inflammatory and pro-thrombotic profile
      than adult ECFC. These preliminary data offer level-headed evidence to use cord
      blood ECFC as a cell therapy product in vascular diseases.

PMID- 23867185
TI  - Visceral leishmaniasis presenting with paroxysmal cold haemoglobinuria.

PMID- 23867181
TI  - Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the
      2013 update of the "Seville Document".

PMID- 23867186
TI  - Use of platelet-rich plasma in the care of sports injuries: our experience with
      ultrasound-guided injection.
AB  - BACKGROUND: Platelet-rich plasma is being used more frequently to promote healing
      of muscle injuries. The growth factors contained in platelet-rich plasma
      accelerate physiological healing processes and the use of these factors is simple
      and minimally invasive. The aim of this study was to demonstrate the efficacy of
      ultrasound-guided injection of platelet-rich plasma in muscle strains and the
      absence of side effects. MATERIALS AND METHODS: Fifty-three recreational athletes
      were enrolled in the study. The patients were recruited from the Emergency Room
      in the University Hospital at Parma according to a pre-defined protocol. Every
      patient was assessed by ultrasound imaging to evaluate the extent and degree of
      muscle injuries. Only grade II lesions were treated with three ultrasound-guided
      injections of autologous platelet-rich plasma every 7 days. Platelet concentrate
      was produced according to standard methods, with a 10% variability in platelet
      count. The platelet gel for clinical use was obtained by adding thrombin to the
      concentrates under standardised conditions. Outcomes assessed were: pain
      reduction, muscle function recovery and return to sports activity, ultrasound
      imaging tissue healing, relapses, local infections, and any side effect during
      the treatment. RESULTS: In all cases muscle lesions healed fully on ultrasound
      imaging, the pain disappeared, and muscle function recovery was documented with a
      return to sports activity. A single patient had a relapse 1 year after treatment.
      DISCUSSION: Platelet-rich plasma injected into the injury site is one of the most
      important factors rendering the treatment effective. To maximise its efficacy the
      preliminary ultrasound must be done accurately to localise the lesion and guide
      the needle into the corresponding lesion. According to the current results, which
      document full muscle recovery and no relapse except for one case, platelet-rich
      plasma ultrasound-guided injection represents a valid mini-invasive treatment for
      muscle injuries.

PMID- 23867187
TI  - Response to "Alloimmunisation in thalassaemics: a comparison between recipients
      of usual matched and partial better matched blood. An evaluation at a tertiary
      care centre in India".

PMID- 23867188
TI  - A case of severe foetal anaemia due to anti-M isoimmunisation salvaged by
      intrauterine transfusions.

PMID- 23867189
TI  - Multidisciplinary approach in pregnancy-associated thrombotic thrombocytopenic
      purpura: a case report.

PMID- 23867191
TI  - A collaborative approach to headache classification.

PMID- 23867190
TI  - Human neutrophil antigen-3a antibodies induce neutrophil aggregation in a plasma
      free medium.
AB  - BACKGROUND: Antibodies against the human neutrophil alloantigen-3a (HNA-3a) are
      involved in severe cases of transfusion-related acute lung injury (TRALI), but
      the susceptibility of patients towards HNA-3a antibody differs largely. HNA-3a
      antibodies induce granulocyte aggregation. However, it is unresolved whether
      plasma proteins are required for granulocyte aggregation. MATERIALS AND METHODS:
      We investigated whether HNA-3a-antibody-induced aggregation of polymorphonuclear
      cells is dependent on plasma factors by using and modifying the granulocyte
      agglutination test (GAT). RESULTS: Polymorphonuclear cells homozygous for HNA-3a
      did not aggregate when incubated with HNA-3a antibodies in a plasma-protein-free
      GAT setup. When the GAT was performed using polymorphonuclear cells re-suspended
      in phosphate-buffered saline containing proteins, HNA-3-mediated aggregation was
      observed. Moreover, using Tween(r) 20 for blocking the plates, reconstituted the
      granulocyte aggregation in a protein-free medium. This indicates that granulocyte
      aggregation probably occurs by direct granulocyte-granulocyte interaction(s) or
      is mediated by substances released by neutrophils after activation. DISCUSSION:
      Granulocyte aggregation induced by HNA-3a antibodies does not require human
      plasma proteins. Interindividual variability in the response to HNA-3a antibodies
      does not depend on differences in patient's plasma proteins.

PMID- 23867192
TI  - Restless legs syndrome and cerebrovascular disease - authors' reply.

PMID- 23867193
TI  - Restless legs syndrome and cerebrovascular disease.

PMID- 23867194
TI  - Microbleeds in cerebral small vessel disease.

PMID- 23867195
TI  - Microbleeds in cerebral small vessel disease - authors' reply.

PMID- 23867196
TI  - Three decades of caring for the Venezuelan Huntington's disease families.

PMID- 23867198
TI  - Advances in clinical and molecular understanding of the FMR1 premutation and
      fragile X-associated tremor/ataxia syndrome.
AB  - Fragile X syndrome, the most common heritable form of cognitive impairment, is
      caused by epigenetic silencing of the fragile X (FMR1) gene owing to large
      expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, so-called
      premutation expansions (55-200 repeats) can cause a family of neurodevelopmental
      phenotypes (attention deficit hyperactivity disorder, autism spectrum disorder,
      seizure disorder) and neurodegenerative (fragile X-associated tremor/ataxia
      syndrome [FXTAS]) phenotypes through an entirely distinct molecular mechanism
      involving increased FMR1 mRNA production and toxicity. Results of basic cellular,
      animal, and human studies have helped to elucidate the underlying RNA toxicity
      mechanism, while clinical research is providing a more nuanced picture of the
      range of clinical manifestations. Advances of knowledge on both mechanistic and
      clinical fronts are driving new approaches to targeted treatment, but two
      important necessities are emerging: to define the extent to which the mechanisms
      contributing to FXTAS also contribute to other neurodegenerative and medical
      disorders, and to redefine FXTAS in view of its differing presentations and
      associated features. 

PMID- 23867199
TI  - New experimental and clinical links between the hippocampus and the dopaminergic
      system in Parkinson's disease.
AB  - Parkinson's disease is a common progressive neurodegenerative disease, of which
      the main neuropathological hallmark is dopaminergic neuronal loss. Increased
      attention has been directed towards non-motor symptoms in Parkinson's disease,
      such as cognitive impairment and behavioural disorders. Clinical and experimental
      findings support the view that the hippocampus, a temporal lobe structure
      involved in physiological learning and memory, is also implicated in the
      cognitive dysfunction seen in some patients with Parkinson's disease. Moreover,
      emerging data suggest interactions between the dopaminergic systems and the
      hippocampus in synaptic plasticity, adaptive memory, and motivated behaviour.
      This structure is also implicated in the pathophysiology of other non-motor
      symptoms, such as impulse control disorders, anosmia, and fatigue. Evidence from
      clinical observations and experimental studies suggest a complex hippocampal
      cross-talk among the dopaminergic and other transmitter systems. Furthermore,
      neurotrophic factors might interact with the hippocampal dopaminergic system
      having possible implications on the non-motor symptoms seen in patients with
      Parkinson's disease. 

PMID- 23867200
TI  - Neuroimaging standards for research into small vessel disease and its
      contribution to ageing and neurodegeneration.
AB  - Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features
      seen on neuroimaging include recent small subcortical infarcts, lacunes, white
      matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD
      can present as a stroke or cognitive decline, or can have few or no symptoms. SVD
      frequently coexists with neurodegenerative disease, and can exacerbate cognitive
      deficits, physical disabilities, and other symptoms of neurodegeneration.
      Terminology and definitions for imaging the features of SVD vary widely, which is
      also true for protocols for image acquisition and image analysis. This lack of
      consistency hampers progress in identifying the contribution of SVD to the
      pathophysiology and clinical features of common neurodegenerative diseases. We
      are an international working group from the Centres of Excellence in
      Neurodegeneration. We completed a structured process to develop definitions and
      imaging standards for markers and consequences of SVD. We aimed to achieve the
      following: first, to provide a common advisory about terms and definitions for
      features visible on MRI; second, to suggest minimum standards for image
      acquisition and analysis; third, to agree on standards for scientific reporting
      of changes related to SVD on neuroimaging; and fourth, to review emerging imaging
      methods for detection and quantification of preclinical manifestations of SVD.
      Our findings and recommendations apply to research studies, and can be used in
      the clinical setting to standardise image interpretation, acquisition, and
      reporting. This Position Paper summarises the main outcomes of this international
      effort to provide the STandards for ReportIng Vascular changes on nEuroimaging
      (STRIVE). 

PMID- 23867201
TI  - AKT in stromal fibroblasts controls invasion of epithelial cells.
AB  - The tumour microenvironment has an important role in cancer progression and
      recent reports have proposed that stromal AKT is activated and regulates
      tumourigenesis and invasion. We have shown, by immuno-fluorescent analysis of oro
      pharyngeal cancer biopsies, an increase in AKT activity in tumour associated
      stromal fibroblasts compared to normal stromal fibroblasts. Using organotypic
      raft co-cultures, we show that activation of stromal AKT can induce the invasion
      of keratinocytes expressing the HPV type 16 E6 and E7 proteins, in a Keratinocyte
      Growth Factor (KGF) dependent manner. By depleting stromal fibroblasts of each of
      the three AKT isoforms independently, or through using isoform specific
      inhibitors, we determined that stromal AKT2 is an essential regulator of invasion
      and show in oro-pharyngeal cancers that AKT2 specific phosphorylation events are
      also identified in stromal fibroblasts. Depletion of stromal AKT2 inhibits
      epithelial invasion through activating a protective pathway counteracting KGF
      mediated invasions. AKT2 depletion in fibroblasts stimulates the cleavage and
      release of IL1B from stromal fibroblasts resulting in down-regulation of the KGF
      receptor (fibroblast growth factor receptor 2B (FGFR2B)) expression in the
      epithelium. We also show that high IL1B is associated with increased overall
      survival in a cohort of patients with oro-pharyngeal cancers. Our findings
      demonstrate the importance of stromal derived growth factors and cytokines in
      regulating the process of tumour cell invasion. 

PMID- 23867202
TI  - The kinetics of invertin action. 1913.

PMID- 23867203
TI  - Is there an alternative to the surgical above-knee bypass in treatment of
      superficial femoral artery disease? Experiences with Viabahn stent graft.
AB  - OBJECTIVE: We conducted a retrospective study to compare short- and mid-term
      patencies of Viabahn with surgical above-knee prosthetic bypass (pAKB). METHODS:
      The records of 52 patients with either pAKB (n = 25) or Viabahn (n = 27) were
      reviewed. The majority had Rutherford clinical grade 3. Patients were followed
      after 3, 6, and 12 months and yearly thereafter. RESULTS: For Viabahn, the short
      term (1-16 months) primary patency rate was 60% with a secondary patency rate of
      90%, and mid-term (1-68 months) patencies of 47% and 83.3%, respectively. In
      pAKB, the short-term results revealed a primary patency rate of 78% with a
      secondary patency of 91% and mid-term results of 65% and 90%, respectively. No
      statistical difference was found concerning short-term patencies. Mid-term
      primary patency was lower for Viabahn (P < .05) and secondary patency proved no
      significant difference. CONCLUSION: Viabahn revealed similar short-term primary
      and secondary patencies but lower mid-term primary patency. It provides a good
      alternative therapy to pAKB.

PMID- 23867204
TI  - Expression dynamics of RpoS/Crl-dependent genes in Escherichia coli.
AB  - The alternative sigma factor RpoS is a central regulator of the stress response
      in many Proteobacteria, acting both during exponential growth and in stationary
      phase. The small protein Crl increases the interaction between RpoS and RNA
      polymerase and thereby activates certain RpoS-dependent promoters. However, the
      growth-phase dependence of the interaction of Crl with different forms of
      polymerase remains unknown. We use 41 GFP transcriptional fusions to study the
      dynamics of gene regulation by RpoS and Crl during growth transition from
      exponential to stationary phase in Escherichia coli. We confirm that RpoS can
      regulate gene expression in exponential phase, both positively and negatively.
      Crl slightly stimulates transcription by RpoS in exponential phase and controls a
      subset of RpoS-dependent genes in stationary phase. Growth temperature strongly
      affects induction of specific promoters by RpoS, whereas its impact on gene
      regulation by Crl is much less significant. In addition, we identify five new
      genes regulated by Crl (ada, cbpA, glgS, sodC and flgM) and demonstrate that Crl
      improves promoter binding and opening by RpoS-containing RNA polymerase at the
      hdeA promoter. Our study also shows that Crl is a cognate enhancer of RpoS
      activity under different growth conditions, since its deletion has no effect on
      genes transcribed by other sigma factors. 

PMID- 23867205
TI  - The eIF4E subunits of two distinct trypanosomatid eIF4F complexes are subjected
      to differential post-translational modifications associated to distinct growth
      phases in culture.
AB  - The eukaryotic eIF4F complex, the cap binding complex, functions during
      translation initiation through interactions mediated by its three subunits
      (eIF4E, eIF4G and eIF4A), other initiation factors and the ribosome. In
      trypanosomatids, various eIF4E and eIF4G homologues were identified, with two
      eIF4F-like complexes confirmed (EIF4E4/EIF4G3/EIF4AI and EIF4E3/EIF4G4/EIF4AI).
      Here, the expression pattern of these complexes was investigated during
      Leishmania amazonensis and Trypanosoma brucei growth. The two sets of eIF4E and
      eIF4G homologues were found represented by phosphorylated isoforms with multiple
      phosphorylation events targeting the two eIF4E homologues. Expression of these
      multiple isoforms was differentially affected by inhibitors of mRNA
      synthesis/processing and translation. Phosphorylated EIF4E4 was consistently
      associated with early/active growth phases in both organisms studied. In T.
      brucei phosphorylation of both EIF4E3 and 4, overexpressed as HA-tagged fusions,
      was partially mapped to their N-terminuses. Our results indicate that
      phosphorylation is associated with a further layer of complexity in translation
      initiation in trypanosomatids. 

PMID- 23867206
TI  - Decreased microRNA-221 is associated with high levels of TNF-alpha in human
      adipose tissue-derived mesenchymal stem cells from obese woman.
AB  - AIM: The present study aimed to investigate the regulation and involvement of miR
      221 in the differentiation of human adipose tissue-derived mesenchymal stem cells
      (hASCs). The relationships between miR-221 and pro-inflammatory markers and
      adipokines were also explored. METHODS: Eight adipose tissues were obtained from
      four obese (mean body mass index (BMI) =31.7 kg/m(2)) and four lean (mean BMI=
      21.5 kg/m(2)) women. hASCs were induced to differentiate, and the related gene
      expression were measured in the hASC-differentiated adipocytes using real-time
      reverse transcriptase polymerase chain reaction (real-time RT-PCR). RESULTS:
      During adipogenesis, miR-221 was significantly down-regulated; furthermore, miR
      221 levels were lower in hASC-differentiated adipocytes from obese subjects than
      in the corresponding adipocytes from lean subjects. Higher TNF-alpha mRNA levels
      were associated with lower levels of miR-221. In addition, the miR-221 levels in
      the adipocytes were inversely correlated with BMI. CONCLUSION: Our results
      support the link between miR-221 and obesity development as well as obesity
      related inflammatory status.

PMID- 23867207
TI  - Nutritional assessment and treatment of patients with liver cirrhosis.
AB  - Prevalence of chronic liver diseases, including liver cirrhosis, is increasing
      worldwide. The nutritional state assessment in these patients is complicated, and
      besides anthropometry is based on several other tools in order to be more
      accurate. Specific dietary recommendations are needed in patients with chronic
      liver diseases in order to help prevent and treat liver decompensation because
      malnutrition is an independent predictor of mortality. This review focuses on
      essential aspects in the nutritional assessment of cirrhotic patients and some
      general recommendations for their treatment. 

PMID- 23867208
TI  - Effect of short-term administration of cinnamon on blood pressure in patients
      with prediabetes and type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to systematically review and evaluate the
      effect of short-term administration of cinnamon on blood pressure regulation in
      patients with prediabetes and type 2 diabetes by performing a meta-analysis of
      randomized, placebo-controlled clinical trials. METHODS: Medical literature for
      randomized controlled trials (RCTs) of the effect of cinnamon on blood pressure
      was systematically searched; three original articles published between January
      2000 and September 2012 were identified from the MEDLINE database and a hand
      search of the reference lists of the articles obtained through MEDLINE. The
      search terms included cinnamon or blood pressure or systolic blood pressure (SBP)
      or diastolic blood pressure (DBP) or diabetes. A random effects model was used to
      calculate weighted mean difference and 95% confidence intervals (CI). RESULTS:
      The pooled estimate of the effect of cinnamon intake on SBP and DBP demonstrated
      that the use of cinnamon significantly decreased SBP and DBP by 5.39 mm Hg (95%
      CI, -6.89 to -3.89) and 2.6 mm Hg (95% CI, -4.53 to -0.66) respectively.
      CONCLUSION: Consumption of cinnamon (short term) is associated with a notable
      reduction in SBP and DBP. Although cinnamon shows hopeful effects on BP-lowering
      potential, it would be premature to recommend cinnamon for BP control because of
      the limited number of studies available. Thus, undoubtedly a long-term,
      adequately powered RCT involving a larger number of patients is needed to
      appraise the clinical potential of cinnamon on BP control among patients with
      type 2 diabetes mellitus.

PMID- 23867209
TI  - Perioperative synbiotic therapy in elderly patients undergoing
      gastroenterological surgery: a prospective, randomized control trial.
AB  - OBJECTIVE: Enteral administration of synbiotics has been reported to be
      beneficial during various types of surgery, but its clinical value in elderly
      surgical patients remains unclear. The aim of this study was to quantitatively
      evaluate the changes in gut microbiota and environment induced by perioperative
      synbiotic therapy, and to investigate whether it is possible to reduce infectious
      complications in elderly patients undergoing gastroenterological surgery.
      METHODS: Forty-eight patients over the age of 70 y were randomized into a group
      receiving 7 d of preoperative and 10 d of postoperative synbiotic therapy (S
      group) and a control group without synbiotic therapy (C group). A fecal sample
      collected before and after surgery in each group was used for a quantitative
      evaluation of the microbiota. RESULTS: Forty-eight patients completed the trial
      (25 in the S group and 23 in the C group). Synbiotic therapy significantly
      maintained the status of Bifidobacterium and Lactobacillus, whereas the number of
      Enterobacteriaceae, Staphylococcus, and Pseudomonas was significantly decreased.
      The total organic acid and short-chain fatty acid concentrations were increased,
      and the pH was markedly decreased, in the S group compared with the C group. The
      incidence of postoperative infectious complications was 12% in the S group and
      36% in the C group, however, the difference did not reach statistical
      significance (P = 0.06). A multivariate analysis revealed that only the use of
      perioperative blood transfusion was an independent risk factor for infectious
      complications. CONCLUSIONS: Synbiotic therapy improved the intestinal microbial
      environment, and might decrease the incidence of infectious complications in
      elderly surgical patients.

PMID- 23867210
TI  - Denosumab treatment of giant cell tumour of bone.

PMID- 23867211
TI  - Safety and efficacy of denosumab for adults and skeletally mature adolescents
      with giant cell tumour of bone: interim analysis of an open-label, parallel
      group, phase 2 study.
AB  - BACKGROUND: Giant cell tumour of bone (GCTB) is a very rare, aggressive, and
      progressive osteolytic tumour for which no standard medicinal treatment or
      chemotherapy exists. We report interim safety and efficacy results from a phase 2
      study of denosumab in patients with GCTB. METHODS: We did an international, open
      label, parallel-group, phase 2 trial of patients with histologically confirmed
      GCTB and radiographically measurable active disease. Eligible patients were
      adults or skeletally mature adolescents with radiographic evidence of at least
      one mature long bone who were at least 12 years old and weighed at least 45 kg.
      We divided patients into three cohorts--those with surgically unsalvageable GCTB
      (cohort 1), those with salvageable GCTB whose surgery was associated with severe
      morbidity (cohort 2), and those who transferred from a previous study of
      denosumab for GCTB (cohort 3). Patients in cohorts 1 and 2 received 120 mg of
      subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the
      first cycle; those in cohort 3 continued the regimen from the previous study.
      Investigator-determined disease status and clinical benefit were assessed every 4
      weeks. Our primary endpoint was the safety profile of denosumab in terms of
      adverse events and laboratory abnormalities. Prespecified secondary endpoints
      were time to disease progression in cohort 1 and the proportion of patients
      without any surgery at 6 months in cohort 2. Safety analyses included all
      patients who received at least one dose of denosumab. Efficacy analyses included
      all eligible patients who received at least one dose of denosumab. This study is
      registered with ClinicalTrials.gov, identifier NCT00680992. FINDINGS: 282
      patients, including ten adolescents, were included between Sept 9, 2008, and
      March 25, 2011. Of the 281 patients analysable for safety, three (1%) had
      osteonecrosis of the jaw and 15 (5%) hypocalcaemia. The most common grade 3-4
      adverse events were hypophosphataemia, which occurred in nine (3%) patients, and
      anaemia, back pain, and pain in extremities, each of which occurred in three
      patients (1%). Serious adverse events were reported in 25 (9%) patients. No
      treatment-related deaths were reported. On the basis of investigators' assessment
      of disease status, 163 of 169 (96%) analysable patients in cohort 1 had no
      disease progression after median follow-up of 13 months (IQR 5.8-21.0). In cohort
      2, 74 of 100 (74%) analysable patients had no surgery and 16 of 26 (62%) patients
      who had surgery underwent a less morbid procedure than planned. Median follow-up
      in cohort 2 was 9.2 months (IQR 4.2-12.9). INTERPRETATION: Adverse events were
      consistent with the known safety profile of denosumab. Denosumab was associated
      with tumour responses and reduced the need for morbid surgery in patients with
      GCTB. Denosumab represents a new treatment option for patients with GCTB.
      FUNDING: Amgen.

PMID- 23867213
TI  - Interactions between human immunodeficiency virus type 1 and polymorphonuclear
      neutrophils.
AB  - Polymorphonuclear neutrophils (PMN) are the most abundant circulating leukocytes.
      They represent a first line of innate immunity against a large panel of microbial
      pathogens, pending development of specific immune responses. The role of PMN in
      human immunodeficiency virus type 1 (HIV-1) disease has mainly been investigated
      from the point of view of the increased susceptibility of HIV-1-infected patients
      to bacterial and fungal infections. However, it is now clear that the
      relationship between PMN and HIV-1 is far more complex. This review examines both
      the beneficial and the detrimental effects of PMN during HIV infection.

PMID- 23867212
TI  - DNA in motion during double-strand break repair.
AB  - DNA organization and dynamics profoundly affect many biological processes such as
      gene regulation and DNA repair. In this review, we present the latest studies on
      DNA mobility in the context of DNA damage. Recent studies demonstrate that DNA
      mobility is dramatically increased in the presence of double-strand breaks (DSBs)
      in the yeast Saccharomyces cerevisiae. As a consequence, chromosomes explore a
      larger nuclear volume, facilitating homologous pairing but also increasing the
      rate of ectopic recombination. Increased DNA dynamics is dependent on several
      homologous recombination (HR) proteins and we are just beginning to understand
      how chromosome dynamics is regulated after DNA damage. 

PMID- 23867214
TI  - Insulin hypersecretion in islets from diet-induced hyperinsulinemic obese female
      mice is associated with several functional adaptations in individual beta-cells.
AB  - Insulin resistance and hyperinsulinemia are generally associated with obesity.
      Obese nondiabetic individuals develop a compensatory beta-cell response to adjust
      insulin levels to the increased demand, maintaining euglycemia. Although several
      studies indicate that this compensation relies on structural changes, the
      existence of beta-cell functional adaptations is incompletely understood. Here,
      we fed female mice with a high-fat diet (HFD) for 12 weeks. These animals became
      obese, hyperinsulinemic, insulin-resistant, and mildly glucose-intolerant while
      fed, and fasting glycemia was comparable in HFD and control mice. Islets from HFD
      animals exhibited increased beta-cell mass and hypertrophy. Additionally, they
      had enhanced insulin gene expression and content and augmented glucose-induced
      insulin secretion. Electrophysiological examination of beta-cells from both
      groups showed no differences in KATP channel open probability and conductance.
      However, action potentials elicited by glucose had larger amplitude in obese
      mice. Glucose-induced Ca2+ signals in intact islets, in isolated beta-cells, and
      individual beta-cells within islets were also increased in HFD mice.
      Additionally, a higher proportion of glucose-responsive cells was present in
      obese mice. In contrast, whole-cell Ca2+ current densities were similar in both
      groups. Capacitance measurements showed that depolarization-evoked exocytosis was
      enhanced in HFD beta-cells compared with controls. Although this augment was not
      significant when capacitance increases of the whole beta-cell population were
      normalized to cell size, the exocytotic output varied significantly when beta
      cells were distributed by size ranges. All these findings indicate that beta-cell
      functional adaptations are present in the islet compensatory response to obesity.

PMID- 23867215
TI  - Regulation of pituitary tumor transforming gene (PTTG) expression and
      phosphorylation in thyroid cells.
AB  - Human pituitary tumor transforming gene (hPTTG) is a multifunctional proto
      oncogene implicated in the initiation and progression of several tumors.
      Phosphorylation of hPTTG is mediated by cyclin-dependent kinase 2 (CDC2), whereas
      cellular expression is regulated by specificity protein 1 (SP1). The mechanisms
      underlying hPTTG propagation of aberrant thyroid cell growth have not been fully
      defined. We set out to investigate the interplay between hPTTG and growth
      factors, as well as the effects of phosphorylation and SP1 regulation on hPTTG
      expression and function. In our study, epidermal growth factor (EGF), TGFalpha,
      and IGF-1 induced hPTTG expression and phosphorylation in thyroid cells, which
      was associated with activation of MAPK and phosphoinositide 3-kinase. Growth
      factors induced hPTTG independently of CDC2 and SP1 in thyroid carcinoma cells.
      Strikingly, CDC2 depletion in TPC-1 cells resulted in enhanced expression and
      phosphorylation of hPTTG and reduced cellular proliferation. In reciprocal
      experiments, hPTTG overexpression induced EGF, IGF-1, and TGFalpha mRNAs in
      primary human thyrocytes. Treatment of primary human thyrocytes with conditioned
      media derived from hPTTG-transfected cells resulted in autocrine upregulation of
      hPTTG protein, which was ameliorated by growth factor depletion or growth factor
      receptor tyrosine kinase inhibitors. A transgenic murine model of thyroid
      targeted hPTTG overexpression (hPTTG-Tg) (FVB/N strain, both sexes) demonstrated
      smaller thyroids with reduced cellular proliferation and enhanced secretion of
      Egf. In contrast, Pttg(-/-) knockout mice (c57BL6 strain, both sexes) showed
      reduced thyroidal Egf mRNA expression. These results define hPTTG as having a
      central role in thyroid autocrine signaling mechanisms via growth factors, with
      profound implications for promotion of transformed cell growth. 

PMID- 23867216
TI  - Spinning and translational motion of Sb nanoislands manipulated on MoS2.
AB  - Antimony nanoislands grown on a MoS2 surface in ultra-high vacuum have been
      manipulated by atomic force microscopy (AFM) in ambient conditions. The island
      profiles have been digitized and provided as an input to a collisional algorithm
      based on classical mechanics. Assuming that the islands are rigid and static
      friction is high enough to prevent further motion after the passage of the
      probing tip, the direction of motion and the angle of rotation of the islands
      have been reproduced numerically. For a given spacing between the scan lines, the
      angle of deflection with respect to the fast scan direction and the angular speed
      of the islands are expected to vary with the friction between islands and
      substrate. From a comparison between model and experiment a shear strength in the
      order of 0.2 MPa is estimated. 

PMID- 23867217
TI  - Effects of interleukin-6 on the expression of tight junction proteins in isolated
      cerebral microvessels from yearling and adult sheep.
AB  - OBJECTIVES: The blood-brain barrier is a selective diffusion barrier between
      brain parenchyma and the intravascular compartment. Tight junctions are integral
      components of the blood-brain barrier. Pro-inflammatory cytokines are important
      in the pathogenesis of brain injury and could modify the protein constituents of
      tight junctions. We hypothesized that interleukin-6 (IL-6) downregulates key
      protein constituents of endothelial tight junctions (e.g. occludin and claudin
      5). METHODS: We examined the effects of IL-6 on tight junction protein expression
      using an in vitro blood-brain barrier model. We isolated microvessels from
      yearling and adult ovine cerebral cortex and placed them into culture with IL-6
      concentrations of 0 (control, phosphate-buffered saline), 1, 10, and 100 ng/ml
      for 24 h. Cerebral microvessels were harvested, Western immunoblot performed for
      occludin and claudin-5, densitometry performed, and results expressed as a ratio
      to control values. RESULTS: Western immunoblot analysis showed that treatment
      with 100 ng/ml of IL-6, but not the lower concentrations, reduced (p < 0.05)
      occludin expression in microvessels from yearling and adult sheep and claudin-5
      in microvessels from adult sheep. However, treatment with 10 ng/ml of IL-6
      increased claudin-5 in microvessels from yearling sheep. The percent of lactate
      dehydrogenase released from the microvessels into the surrounding media was not
      increased by IL-6 treatment, suggesting that the reductions in tight junction
      proteins did not result from cell death. Treatment of adult cerebral cortical
      microvessels with IL-6 preincubated with anti-IL-6 monoclonal antibodies
      partially attenuated the reduction in claudin-5. CONCLUSION: We conclude that IL
      6 modulates tight junction protein expression in cerebral cortical microvessels
      from yearling and adult sheep.

PMID- 23867218
TI  - Complications of vagal nerve stimulation for drug-resistant epilepsy: a single
      center longitudinal study of 143 patients.
AB  - PURPOSE: To longitudinally study surgical and hardware complications to vagal
      nerve stimulation (VNS) treatment in patients with drug-resistant epilepsy.
      METHODS: In a longitudinal retrospective study, we analyzed surgical and hardware
      complications in 143 patients (81 men and 62 women) who between 1994 and 2010
      underwent implantation of a VNS-device for drug-resistant epilepsy. The mean
      follow-up time was 62 +/- 46 months and the total number of patient years 738.
      RESULTS: 251 procedures were performed on 143 patients. 16.8% of the patients
      were afflicted by complications related to surgery and 16.8% suffered from
      hardware malfunctions. Surgical complications were: superficial infection in
      3.5%, deep infection needing explantation in 3.5%, vocal cord palsy in 5.6%,
      which persisted in at least 0.7% for over one year, and other complications in
      5.6%. Hardware-related complications were: lead fracture in 11.9% of patients,
      disconnection in 2.8%, spontaneous turn-off in 1.4% and stimulator malfunction in
      1.4%. We noted a tendency to different survival times between the two most
      commonly used lead models as well as a tendency to increased infection rate with
      increasing number of stimulator replacements. CONCLUSION: In this series we
      report on surgical and hardware complications from our 16 years of experience
      with VNS treatment. Infection following insertion of the VNS device and vocal
      cord palsy due to damage to the vagus nerve are the most serious complications
      related to the surgery. Avoiding unnecessary reoperations in order to reduce the
      appearances of these complications are of great importance. It is therefore
      essential to minimize technical malfunctions that will lead to additional
      surgery. Further studies are needed to evaluate the possible superiority of the
      modified leads.

PMID- 23867219
TI  - Prostate cancer metastases alter bone mineral and matrix composition independent
      of effects on bone architecture in mice--a quantitative study using microCT and
      Raman spectroscopy.
AB  - Prostate cancer is the most common primary tumor and the second leading cause of
      cancer-related deaths in men in the United States. Prostate cancer bone
      metastases are characterized by abnormal bone remodeling processes and result in
      a variety of skeletal morbidities. Prevention of skeletal complications is a
      crucial element in prostate cancer management. This study investigated prostate
      cancer-induced alterations in the molecular composition and morphological
      structure of metastasis-bearing bones in a mouse model of prostate cancer using
      Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate
      cancer cells were injected into the right tibiae of 5-week old male SCID mice.
      Upon sacrifice at 8weeks post tumor inoculation, two out of the ten tumor-bearing
      tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions
      only and 4 mixed with osteoblastic and osteolytic lesions. Carbonate substitution
      was significantly increased while there was a marked reduction in the level of
      collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the
      cortex of the intact tumor-bearing tibiae compared to contralateral controls.
      MicroCT analysis revealed a significant reduction in bone volume/total volume,
      trabecular number and trabecular thickness, as well as significant increase in
      bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active
      bone remodeling and bone loss. None of the changes in bone compositional
      properties were correlated with lesion area from radiographs or the changes in
      bone architecture from microCT. This study indicates that LNCaP C4-2B prostate
      cancer metastases alter bone tissue composition independent of changes in
      architecture, and altered bone quality may be an important contributor to
      fracture risk in these patients. Raman spectroscopy may provide a new avenue of
      investigation into interactions between tumor and bone microenvironment. 

PMID- 23867220
TI  - Biomechanical properties of bone treated by magnetic resonance-guided focused
      ultrasound - an in vivo porcine model study.
AB  - The magnetic resonance-guided focused ultrasound (MRgFUS) system uses MR imaging
      for real-time aiming of thermal ablation of bone and soft tissue tumors. Past
      clinical studies showed no increase in fracture rate after MRgFUS treatment. The
      purpose of this study was to determine the effect of MRgFUS treatment on
      mechanical properties of bone and correlate the effect to histological findings
      of treated bone. Four fully grown mini-pigs were treated by MRgFUS. Six
      consecutive right normal ribs were treated in each animal, and the left
      corresponding ribs served as controls. The animals were sacrificed at pre-set
      intervals (0, 2, 6 and 12weeks after treatment), and the treated and control
      bones were extracted. Mechanical properties of each bone were examined using
      three points bending studies for comparing treated bones to the corresponding
      controls. Histologic properties using Masson and hematoxylin-eosin stains were
      also compared. The ratio between treated and control biomechanical properties
      showed reduction in bone biomechanical properties at 6weeks post-MRgFUS
      treatment. The mean+/-SD yield load ratio and maximum ratios were 0.69+/-0.11 and
      0.71+/-0.13, respectively (both p=0.031). These findings showed some recovery
      trend at 12weeks after treatment. Histological analysis showed a reduction in
      mean osteon size at 2weeks after treatment (0.58*10(-3)+/-0.1*10(-3)mm and
      0.16*10(-3)+/-0.017*10(-3)mm) in control vs. treated bones, respectively
      (p=0.005). Treatment with the MRgFUS system resulted in a ~30% reduction in
      mechanical strength at 6weeks post-treatment. The reduction showed a reversible
      trend, with a 25%-20% decrease in strength at 12weeks post-treatment. 

PMID- 23867221
TI  - MicroRNA-124 regulates osteoclast differentiation.
AB  - Osteoclasts are specialized cells for bone-resorption originated from precursors
      of macrophage/monocyte lineage. The receptor activator of NFkappaB ligand (RANKL)
      initiates osteoclast differentiation, in which nuclear factor of activated T cell
      cytoplasmic 1 (NFATc1) plays a key role as a master transcription factor. In the
      present report, we show that microRNA-124 (miR-124) regulates osteoclastogenesis
      of mouse bone marrow macrophages (BMMs) by suppressing NFATc1 expression. On the
      other hand, synthetic inhibitor that binds specifically to miR-124 enhanced
      osteoclast differentiation and NFATc1 expression. The overexpression of a
      constitutively active form of NFATc1 prevented the inhibitory effect of miR-124
      on osteoclastogenesis. Finally, miR-124 also affected the proliferation and
      motility of osteoclast precursors, the latter coinciding with the reduced
      expression of RhoA and Rac1. These findings not only reveal unprecedented role of
      miR-124 in osteoclastogenesis but also suggest a novel mode of regulation of
      NFATc1 in osteoclasts. 

PMID- 23867222
TI  - Clinical trials of health information technology interventions intended for
      patient use: unique issues and considerations.
AB  - BACKGROUND: Despite the proliferation of health information technology (IT)
      interventions, descriptions of the unique considerations for conducting
      randomized trials of health IT interventions intended for patient use are
      lacking. PURPOSE: Our purpose is to describe the protocol to evaluate Pocket PATH
      (Personal Assistant for Tracking Health), a novel health IT intervention, as an
      exemplar of how to address issues that may be unique to a randomized controlled
      trial (RCT) to evaluate health IT intended for patient use. METHODS: An overview
      of the study protocol is presented. Unique considerations for health IT
      intervention trials and strategies are described to maintain equipoise, to
      monitor data safety and intervention fidelity, and to keep pace with changing
      technology during such trials. LESSONS LEARNED: The sovereignty granted to
      technology, the rapid pace of changes in technology, ubiquitous use in health
      care, and obligation to maintain the safety of research participants challenge
      researchers to address these issues in ways that maintain the integrity of
      intervention trials designed to evaluate the impact of health IT interventions
      intended for patient use. CONCLUSIONS: Our experience evaluating the efficacy of
      Pocket PATH may provide practical guidance to investigators about how to comply
      with established procedures for conducting RCTs and include strategies to address
      the unique issues associated with the evaluation of health IT for patient use.

PMID- 23867223
TI  - Concealment and fabrication by experienced research subjects.
AB  - BACKGROUND: Subjects who enroll in multiple studies have been found to use
      deception at times to overcome restrictive screening criteria. Deception
      undermines subject safety as well as study integrity. Little is known about the
      extent to which experienced research subjects use deception and what type of
      information is concealed, withheld, or distorted. PURPOSE: This study examined
      the prevalence of deception and types of deception used by subjects enrolling in
      multiple studies. METHODS: Self-report of deceptive behavior used to gain entry
      into clinical trials was measured among a sample of 100 subjects who had
      participated in at least two studies in the past year. RESULTS: Three quarters of
      subjects reported concealing some health information from researchers in their
      lifetime to avoid exclusion from enrollment in a study. Health problems were
      concealed by 32% of the sample, use of prescribed medications by 28%, and
      recreational drug use by 20% of the sample. One quarter of subjects reported
      exaggerating symptoms in order to qualify for a study and 14% reported pretending
      to have a health condition in order to qualify. LIMITATIONS: Although this study
      finds high rates of lifetime deceptive behavior, the frequency and context of
      this behavior is unknown. Understanding the context and frequency of deception
      will inform the extent to which it jeopardizes study integrity and safety.
      CONCLUSION: The use of deception threatens both participant safety and the
      integrity of research findings. Deception may be fueled in part by undue
      inducements, overly restrictive criteria for entry, and increased demand for
      healthy controls. Screening measures designed to detect deception among study
      subjects would aid in both protecting subjects and ensuring the quality of
      research findings.

PMID- 23867224
TI  - Atypical cadherin negotiates a turn.
AB  - Planar cell polarity (PCP) signaling is involved in many polarized cell
      behaviors. In this issue of Developmental Cell, Tatin et al. (2013) show that the
      atypical cadherin Celsr1 is transiently localized to cellular protrusions in
      lymphatic endothelial cells and acts to orient valve-forming cells perpendicular
      to the vessel axis.

PMID- 23867225
TI  - The plastic pancreas.
AB  - Pancreas homeostasis is based on replication of differentiated cells in order to
      maintain proper organ size and function under changing physiological demand.
      Recent studies suggest that acinar cells, the most abundant cell type in the
      pancreas, are facultative progenitors capable of reverting to embryonic-like
      multipotent progenitor cells under injury conditions associated with
      inflammation. In parallel, it is becoming apparent that within the endocrine
      pancreas, hormone-producing cells can lose or switch their identity under
      metabolic stress or in response to single gene mutations. This new view of
      pancreas dynamics suggests interesting links between pancreas regeneration and
      pathologies including diabetes and pancreatic cancer. 

PMID- 23867226
TI  - Competitive interactions eliminate unfit embryonic stem cells at the onset of
      differentiation.
AB  - A fundamental question in developmental biology is whether there are mechanisms
      to detect stem cells with mutations that, although not adversely affecting
      viability, would compromise their ability to contribute to further development.
      Here, we show that cell competition is a mechanism regulating the fitness of
      embryonic stem cells (ESCs). We find that ESCs displaying defective bone
      morphogenetic protein signaling or defective autophagy or that are tetraploid are
      eliminated at the onset of differentiation by wild-type cells. This elimination
      occurs in an apoptosis-dependent manner and is mediated by secreted factors.
      Furthermore, during this process, we find that establishment of differential c
      Myc levels is critical and that c-Myc overexpression is sufficient to induce
      competitive behavior in ESCs. Cell competition is, therefore, a process that
      allows recognition and elimination of defective cells during the early stages of
      development and is likely to play important roles in tissue homeostasis and stem
      cell maintenance.

PMID- 23867228
TI  - The effect of monochromatic photostimulation on growth and development of broiler
      birds.
AB  - The only light source for chickens in environmentally controlled houses is an
      artificial one. Thus, source, spectra, intensity and regimen of light
      supplementation became major factors in modern meat type bird management. Light
      spectra affect growth in meat type birds both in ovo and post hatch. Broilers
      photostimulated in ovo with green light gained significantly more weight than
      birds incubated under dark conditions. Furthermore, we defined the cellular and
      molecular events associated with the effect of in ovo green photostimulation on
      muscle growth. We found that in ovo photostimulation have a stimulatory effect on
      the proliferation and differentiation of satellite cells and a promoting effect
      on the uniformity of the muscle fibers in the early post-hatch period. How does
      in ovo photostimulation affect intracellular events, such as proliferation and
      differentiation of muscle cells, leading to post-hatch muscle growth? It is
      possible that the monochromatic green light penetrates the eggshell and has a
      direct effect on the embryo's muscle. We were unable to detect any proliferative
      effect of monochromatic green light on cultured myoblasts derived from standard
      (un-illuminated) E17 embryos and 3-day-old chicks. A more likely explanation is
      that green light indirectly affects myoblast proliferation by activating the
      endocrine system; the latter receives photic cues from the retinal or extra
      retinal photoreceptors. We gathered some evidence to support these findings; we
      have shown a higher expression of growth hormone (GH) receptor mRNA in satellite
      cells derived from green light illuminated chicks. In addition, plasma GH levels
      and IGF-I levels in muscle tissue, were higher in the green group relative to the
      dark one in early post-hatch. Another possible explanation for this phenomenon
      could be that growth factor secretion is activated in response to green light
      photostimulation. Both retinal and extra-retinal photoreceptors are active during
      embryogenesis and can be first detected at E14. Combinations of in ovo and post
      hatch green light photostimulation to broilers and turkeys did not cause
      synergetic effect on growth. In a recent study, we found that in ovo green light
      photostimulation suppresses the green and red opsin receptors gene expression in
      the last three days before hatching, while red light enhances their expression.
      Furthermore, we found that the down-regulation of the green and red opsins in
      response to incubation under monochromatic green lighting lasted up to 9days post
      hatch, suggesting a possible epigenetic effect. 

PMID- 23867227
TI  - Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells
      and repress rod photoreceptors.
AB  - Cone photoreceptors carry out phototransduction in daylight conditions and
      provide the critical first step in color vision. Despite their importance, little
      is known about the developmental mechanisms involved in their generation,
      particularly how they are determined relative to rod photoreceptors, the cells
      that initiate vision in dim light. Here, we report the identification of a cis
      regulatory module (CRM) for the thyroid hormone receptor beta (Thrb) gene, an
      early cone marker. We found that ThrbCRM1 is active in progenitor cells biased to
      the production of cones and an interneuronal cell type, the horizontal cell (HC).
      Molecular analysis of ThrbCRM1 revealed that it is combinatorially regulated by
      the Otx2 and Onecut1 transcription factors. Onecut1 is sufficient to induce cells
      with the earliest markers of cones and HCs. Conversely, interference with Onecut1
      transcriptional activity leads to precocious rod development, suggesting that
      Onecut1 is critically important in defining cone versus rod fates. 

PMID- 23867229
TI  - Developmental post-natal stress can alter the effects of pre-natal stress on the
      adult redox balance.
AB  - Across diverse vertebrate taxa, stressful environmental conditions during
      development can shape phenotypic trajectories of developing individuals, which,
      while adaptive in the short-term, may impair health and survival in adulthood.
      Regardless, the long-lasting benefits or costs of early life stress are likely to
      depend on the conditions experienced across differing stages of development.
      Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally
      manipulate exposure to stress hormones in developing individuals. We tested the
      hypothesis that interactions occurring between pre- and post-natal developmental
      periods can induce long-term shifts on the adult oxidant phenotype in non
      breeding sexually mature individuals. We showed that early life stress can induce
      long-term alterations in the basal antioxidant defences. The magnitude of these
      effects depended upon the timing of glucocorticoid exposure and upon interactions
      between the pre- and post-natal stressful stimuli. We also found differences
      among tissues with stronger effects in the erythrocytes than in the brain in
      which the long-term effects of glucocorticoids on antioxidant biomarkers appeared
      to be region-specific. Recent experimental work has demonstrated that early life
      exposure to stress hormones can markedly reduce adult survival (Monaghan et al.,
      2012). Our results suggest that long-term shifts in basal antioxidant defences
      might be one of the potential mechanisms driving such accelerated ageing
      processes and that post-natal interventions during development may be a potential
      tool to shape the effects induced by pre-natally glucococorticoid-exposed
      phenotypes. 

PMID- 23867230
TI  - The effects of serotonin, dopamine, gonadotropin-releasing hormones, and
      corazonin, on the androgenic gland of the giant freshwater prawn, Macrobrachium
      rosenbergii.
AB  - Neurotransmitters and neurohormones are agents that control gonad maturation in
      decapod crustaceans. Of these, serotonin (5-HT) and dopamine (DA) are
      neurotransmitters with known antagonist roles in female reproduction, whilst
      gonadotropin-releasing hormones (GnRHs) and corazonin (Crz) are neurohormones
      that exercise both positive and negative controls in some invertebrates. However,
      the effects of these agents on the androgenic gland (AG), which controls
      testicular maturation and male sex development in decapods, via insulin-like
      androgenic gland hormone (IAG), are unknown. Therefore, we set out to assay the
      effects of 5-HT, DA, l-GnRH-III, oct-GnRH and Crz, on the AG of small male
      Macrobrachium rosenbergii (Mr), using histological studies, a BrdU proliferative
      cell assay, immunofluorescence of Mr-IAG, and ELISA of Mr-IAG. The results showed
      stimulatory effects by 5-HT and l-GnRH-III through significant increases in AG
      size, proliferation of AG cells, and Mr-IAG production (P<0.05). In contrast, DA
      and Crz caused inhibitory effects on the AG through significant decreases in AG
      size, proliferation of AG cells, and Mr-IAG production (P<0.05). Moreover, the
      prawns treated with Crz died before day 16 of the experimental period. We propose
      that 5-HT and certain GnRHs can be now used to stimulate reproduction in male M.
      rosenbergii, as they induce increases in AG and testicular size, IAG production,
      and spermatogenesis. The mechanisms by which these occur are part of our on-going
      research. 

PMID- 23867231
TI  - Neuroprotection against traumatic brain injury by xenon, but not argon, is
      mediated by inhibition at the N-methyl-D-aspartate receptor glycine site.
AB  - BACKGROUND: Xenon, the inert anesthetic gas, is neuroprotective in models of
      brain injury. The authors investigate the neuroprotective mechanisms of the inert
      gases such as xenon, argon, krypton, neon, and helium in an in vitro model of
      traumatic brain injury. METHODS: The authors use an in vitro model using mouse
      organotypic hippocampal brain slices, subjected to a focal mechanical trauma,
      with injury quantified by propidium iodide fluorescence. Patch clamp
      electrophysiology is used to investigate the effect of the inert gases on N
      methyl-D-aspartate receptors and TREK-1 channels, two molecular targets likely to
      play a role in neuroprotection. RESULTS: Xenon (50%) and, to a lesser extent,
      argon (50%) are neuroprotective against traumatic injury when applied after
      injury (xenon 43+/-1% protection at 72 h after injury [N=104]; argon 30+/-6%
      protection [N=44]; mean+/-SEM). Helium, neon, and krypton are devoid of
      neuroprotective effect. Xenon (50%) prevents development of secondary injury up
      to 48 h after trauma. Argon (50%) attenuates secondary injury, but is less
      effective than xenon (xenon 50+/-5% reduction in secondary injury at 72 h after
      injury [N=104]; argon 34+/-8% reduction [N=44]; mean+/-SEM). Glycine reverses the
      neuroprotective effect of xenon, but not argon, consistent with competitive
      inhibition at the N-methyl-D-aspartate receptor glycine site mediating xenon
      neuroprotection against traumatic brain injury. Xenon inhibits N-methyl-D
      aspartate receptors and activates TREK-1 channels, whereas argon, krypton, neon,
      and helium have no effect on these ion channels. CONCLUSIONS: Xenon
      neuroprotection against traumatic brain injury can be reversed by increasing the
      glycine concentration, consistent with inhibition at the N-methyl-D-aspartate
      receptor glycine site playing a significant role in xenon neuroprotection. Argon
      and xenon do not act via the same mechanism.

PMID- 23867232
TI  - Volatile anesthetics improve survival after cecal ligation and puncture.
AB  - BACKGROUND: Sepsis remains a leading cause of death in intensive care units.
      There is growing evidence that volatile anesthetics have beneficial
      immunomodulatory effects on complex inflammation-mediated conditions. The authors
      investigated the effect of volatile anesthetics on the overall survival of mice
      in a sepsis model of cecal ligation and puncture (CLP). METHODS: Mice (N = 12 per
      treatment group) were exposed to anesthetic concentrations of desflurane,
      isoflurane, and sevoflurane either during induction of sepsis or when the mice
      showed pronounced symptoms of inflammation. Overall survival, as well as organ
      function and inflammation was compared with the CLP group without intervention.
      RESULTS: With desflurane and sevoflurane conditioning (1.2 minimal alveolar
      concentration for 2 h immediately after induction of CLP) overall survival was
      improved to 58% and 83%, respectively, compared with 17% in the untreated CLP
      group. Isoflurane did not significantly affect outcome. Application of
      sevoflurane 24 h after sepsis induction significantly improved overall survival
      to 66%. CONCLUSIONS: Administration of the volatile anesthetics desflurane and
      sevoflurane reduced CLP-induced mortality. Anesthesia may be a critical
      confounder when comparing study data where different anesthesia protocols were
      used.

PMID- 23867233
TI  - Sleeping to survive?: The impact of volatile anesthetics on mortality in sepsis.

PMID- 23867234
TI  - Cuprizone short-term exposure: astrocytic IL-6 activation and behavioral changes
      relevant to psychosis.
AB  - A growing body of evidence suggests the involvement of inflammatory processes in
      the pathophysiology of schizophrenia. Four- to 8-week exposure to cuprizone, a
      copper chelator, causes robust demyelination and has been used to build a model
      for multiple sclerosis. In contrast, we report here the effects of 1-week
      cuprizone exposure in mice. This short-term cuprizone exposure elicits behavioral
      changes that include augmented responsiveness to methamphetamine and
      phencyclidine, as well as impaired working memory. The cellular effects of 1-week
      cuprizone exposure differ substantially from the longer-term exposure;
      perturbation of astrocytes and microglia is induced without any sign of
      demyelination. Furthermore, the proinflammatory cytokine interleukin-6 was
      significantly up-regulated in glial fibrillary acidic protein (GFAP)-positive
      cells. We propose that this cuprizone short-term exposure may offer a model to
      study some aspects of biology relevant to schizophrenia and related conditions. 

PMID- 23867235
TI  - Oxidative stress in blood in Alzheimer's disease and mild cognitive impairment: a
      meta-analysis.
AB  - Abnormal oxidative stress is an established feature of Alzheimer's disease, but
      clinical trials aiming to reduce oxidative stress have not yet proven an
      effective therapy for dementia patients. The purpose of this review is to
      systematically analyze available data describing markers of oxidative stress and
      antioxidants in blood from subjects with Alzheimer's disease or those with mild
      cognitive impairment to highlight potential interactions between peripheral redox
      changes and central nervous system pathology and contribute to the design of
      future clinical study. PubMed, SCOPUS and Web of Science were systematically
      queried to collect studies which have evaluated markers of oxidative stress,
      levels of antioxidants, copper, transferrin and ceruloplasmin levels in blood
      from subjects with Alzheimer's disease and matched controls. After application of
      quality measures, results were aggregated in a random effects analysis. We found
      that markers of lipid peroxidation are elevated in blood in Alzheimer's disease
      and in mild cognitive impairment, copper metabolism is dysregulated and total
      antioxidant capacity is decreased. While surprisingly none of the major
      antioxidative enzymes are significantly decreased, non-enzymatic antioxidants in
      blood (particularly uric acid, vitamins A, E and C, alpha- and beta-carotene) are
      significantly decreased. There is significant oxidative damage in peripheral
      blood early in the process of neurodegeneration. We propose that clinical studies
      assessing cognitive outcomes after antioxidant therapy tailor interventions to
      individual patients' deficiencies and confirm an improvement in an appropriate
      serological marker of oxidative stress. This strategy may be most effectively
      applied in a clinical trial of primary prevention. 

PMID- 23867238
TI  - Reconstructive surgery in the management of a patient with CLOVES syndrome.

PMID- 23867236
TI  - Glial A30P alpha-synuclein pathology segregates neurogenesis from anxiety-related
      behavior in conditional transgenic mice.
AB  - In Parkinson's disease (PD) patients, alpha-synuclein (alpha-syn) pathology
      advances in form of Lewy bodies and Lewy neurites throughout the brain.
      Clinically, PD is defined by motor symptoms that are predominantly attributed to
      the dopaminergic cell loss in the substantia nigra. However, motor deficits are
      frequently preceded by smell deficiency or neuropsychological symptoms, including
      increased anxiety and cognitive dysfunction. Accumulating evidence indicates that
      aggregation of alpha-syn impairs synaptic function and neurogenic capacity that
      may be associated with deficits in memory, learning and mood. Whether and how
      alpha-syn accumulation contributes to neuropathological events defining these
      earliest signs of PD is presently poorly understood. We used a tetracycline
      suppressive (tet-off) transgenic mouse model that restricts overexpression of
      human A30P alpha-syn to neurons owing to usage of the neuron-specific CaMKIIalpha
      promoter. Abnormal accumulation of A30P correlated with a decreased survival of
      newly generated neurons in the hippocampus and olfactory bulb. Furthermore, when
      A30P alpha-syn expression was suppressed, we observed reduction of the human
      protein in neuronal soma. However, residual dox resistant A30P alpha-syn was
      detected in glial cells within the hippocampal neurogenic niche, concomitant with
      the failure to fully restore hippocampal neurogenesis. This finding is indicative
      to a potential spread of pathology from neuron to glia. In addition, mice
      expressing A30P alpha-syn show increased anxiety-related behavior that was
      reversed after dox treatment. This implies that glial A30P alpha-synucleinopathy
      within the dentate gyrus is part of a process leading to impaired hippocampal
      neuroplasticity, which is, however, not a sole critical event for circuits
      implicated in anxiety-related behavior. 

PMID- 23867239
TI  - Vascularized composite allotransplantation: an update on medical and surgical
      progress and remaining challenges.
AB  - BACKGROUND: In vascularized composite allotransplantation, multiple types of
      tissue are transferred from donor to recipient as a single functional unit. This
      technique has been performed for upper extremity, face, and abdominal wall
      transplants, among many others. OBJECTIVE: To review the existing cases of face
      and upper extremity vascularized composite allotransplantation performed to date
      and to describe the functional outcomes and challenges associated with this new
      procedure. We also review the immune suppression protocols required for these
      procedures. METHODS: A literature review was performed using PubMed and online
      registries where available to identify patients who have undergone upper
      extremity and face transplant procedures. These were compiled and cross
      referenced to abstracts, conference presentations, and press releases in the
      media to create a list of procedures performed to date. RESULTS: More than
      seventy patients have undergone upper extremity transplantation with very good
      functional outcomes routinely achieved. Twenty-five face transplants were
      identified that have been completed to date and details regarding patient outcome
      are included. One cases of human face allotransplantation with pre- and post
      operative images is included as an example of what can be achieved with this
      technique. CONCLUSIONS: Vascularized composite allotransplantation is an emerging
      field that provides an exciting new avenue for reconstructive procedures and
      achieves functional and cosmetic outcomes not previously possible with existing
      techniques. However, it is not without its challenges and considerable work is
      still required prior to widespread adoption of these new reconstructive
      techniques.

PMID- 23867237
TI  - Increased receptor for advanced glycation end product expression in the human
      alcoholic prefrontal cortex is linked to adolescent drinking.
AB  - Adolescence is characterized behaviorally by increased impulsivity and risk
      taking that declines in parallel with maturation of the prefrontal cortex and
      executive function. In the brain, the receptor for advanced glycation end
      products (RAGE) is critically involved in neurodevelopment and neuropathology. In
      humans, the risk of alcoholism is greatly increased in those who begin drinking
      between 13 and 15years of age, and adolescents binge drink more than any other
      age group. We have previously found that alcoholism is associated with increased
      expression of neuroimmune genes. This manuscript tested the hypothesis that
      adolescent binge drinking upregulates RAGE and Toll-like receptor (TLR) 4 as well
      as their endogenous agonist, high-mobility group box 1 (HMGB1).
      Immunohistochemistry, Western blot, and mRNA analyses found that RAGE expression
      was increased in the human post-mortem alcoholic orbitofrontal cortex (OFC).
      Further, an earlier age of drinking onset correlated with increased expression of
      RAGE, TLR4, and HMGB1. To determine if alcohol contributed to these changes, we
      used an adolescent binge ethanol model in rats (5.0g/kg, i.g., 2-day on/2-day off
      from postnatal day [P] 25 to P55) and assessed neuroimmune gene expression. We
      found an age-associated decline of RAGE expression from late adolescence (P56) to
      young adulthood (P80). Adolescent intermittent ethanol exposure did not alter
      RAGE expression at P56, but increased RAGE in the young adult PFC (P80).
      Adolescent intermittent ethanol exposure also increased TLR4 and HMGB1 expression
      at P56 that persisted into young adulthood (P80). Assessment of young adult
      frontal cortex mRNA (RT-PCR) found increased expression of proinflammatory
      cytokines, oxidases, and neuroimmune agonists at P80, 25days after ethanol
      treatment. Together, these human and animal data support the hypothesis that an
      early age of drinking onset upregulates RAGE/TLR4-HMGB1 and other neuroimmune
      genes that persist into young adulthood and could contribute to risk of
      alcoholism or other brain diseases associated with neuroinflammation. 

PMID- 23867240
TI  - Median nerve location change evaluated by ultrasound according to symptom
      severity of carpal tunnel syndrome.

PMID- 23867241
TI  - Research advances on the usage of traditional Chinese medicine for
      neuroprotection in glaucoma.
AB  - Progressive loss of retinal ganglion cells (RGCs) and their axons is the main
      pathogenesis of glaucoma. The cause of glaucoma is not fully understood, but the
      neurodegeneration of glaucoma involves many mechanisms such as oxidative stress,
      glutamate toxicity and ischemia/reperfusion insult. In order to target these
      mechanisms, multiple neuroprotective interventions have been investigated to
      prevent the death of RGCs. Of note are some tonic herbs from the traditional
      Chinese medicine (TCM) pharmacopeia that have shown neuroprotective effects in
      glaucoma. TCM differs from Western medicine in that TCM exhibits complicated
      bioactive components, triggering many signaling pathways and extensive actions on
      vital organs. Modern scientific approaches have demonstrated some of their
      underlying mechanisms. In this review, we used Lycium barbarum and Ginkgo biloba
      as examples to elaborate the characteristics of TCM and their potential
      applications in neuroprotection in glaucoma. 

PMID- 23867242
TI  - Qigong improves balance in young women: a pilot study.
AB  - BACKGROUND: Balance problems are common in people of all ages and can lead to
      falls, thus causing fractures with consequent disability. Qigong practice has
      long been part of daily life in Chinese culture, and has good effects on physical
      health maintenance. OBJECTIVE: The present work describes the change in balance
      in young, healthy women after practising Qigong for eight weeks. DESIGN, SETTING,
      PARTICIPANTS AND INTERVENTIONS: The study took the form of a controlled,
      randomised longitudinal trial, and involved 30 women aged 18-25 years. The
      subjects had no prior experience of Qigong or Tai Chi and were unaware of the
      aims of the study. Subjects were randomly assigned to a Qigong intervention group
      or a control group. Those in the Qigong intervention group performed "exercises
      in 20 figures for health and long-life" (Wang Ziping) for 1 h twice per week, for
      4 weeks. The control group undertook no exercise at all. MAIN OUTCOME MEASURES:
      The main outcome measure was the stabilometry values. These were obtained in a
      unipodal support test, using a plantar pressure platform with optical sensors.
      RESULTS: The Qigong subjects showed a significant improvement in their
      stabilometry results (40.1% pre-intervention and 56.4% post-intervention) (P<
      0.045), while no improvement was seen in the control group (51.2% pre
      intervention and 53.5% post-intervention). At the beginning of the intervention,
      the stabilometry values recorded for the Qigong intervention group were worse
      than those recorded for the control group (40.15% and 51.21% respectively;
      P=0.121). However, a comparison of the post-intervention values between these
      groups showed that these differences have disappeared (P=0.653). CONCLUSION:
      Qigong can improve balance in healthy, young women.

PMID- 23867243
TI  - Extract of buckwheat sprouts scavenges oxidation and inhibits pro-inflammatory
      mediators in lipopolysaccharide-stimulated macrophages (RAW264.7).
AB  - OBJECTIVE: Buckwheat has been considered as a potential source of nutraceutical
      components on the world market of probiotic foodstuffs. The purpose of this study
      was to evaluate the effects of tartary buckwheat (Fagopyrum tataricum) sprouts on
      oxidation and pro-inflammatory mediators. METHODS: The anti-oxidant effects of
      buckwheat extract (BWE) and rutin were evaluated by using 1,1-diphenyl-2
      picrylhydrazyl (DPPH)- and nitric oxide (NO)-scavenging activities, serum
      peroxidation and chelating assays. Lipopolysaccharide (LPS)-stimulated RAW264.7
      cells were used to evaluate anti-inflammatory activities of buckwheat and rutin.
      NO production in LPS-stimulated RAW264.7 cells was determined by using Griess
      reagent. The expressions of inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-kappaB) p65 subunit in
      cytosolic and nuclear portions were determined by Western blot analysis. Also,
      the production of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) was determined by enzyme-linked immunosorbent assay.
      RESULTS: Inhibitory concentration 50 values for DPPH- and NO-scavenging
      activities of BWE were 24.97 and 72.54 MUg/mL respectively. BWE inhibited serum
      oxidation and possessed chelating activity. Furthermore, BWE inhibited IL-6 and
      TNF-alpha production in LPS-stimulated RAW264.7 cells. Also, BWE inhibited iNOS
      and COX-2 expression and NF-kappaB p65 translocation. CONCLUSION: Buckwheat
      sprouts possessed strong antioxidant activity and inhibited production of pro
      inflammatory mediators in the applied model systems. Thus, buckwheat can be
      suggested to be beneficial in inflammatory diseases by inhibiting the free
      radicals and inflammatory mediators.

PMID- 23867244
TI  - Bioactivity of five components of Chinese herbal formula Jiangzhi granules
      against hepatocellular steatosis.
AB  - OBJECTIVE: This study aims to evaluate the bioactivity of five components of the
      traditional Chinese medicine complex prescription Jiangzhi granules against
      hepatocellular steatosis. METHODS: The five major components, including
      protopanaxadiol, tanshinone IIA, emodin, chlorogenic acid, and nuciferine, were
      extracted from Jiangzhi granules. Their cytotoxicity was assessed to determine
      the safe dose of each component for HepG2 cells. HepG2 cellular steatosis was
      induced using 1 mmol/L of free fatty acids (FFAs) for 24 h, and then treated with
      each component at high, intermediate, and low doses (500, 50, and 5 MUmol/L),
      respectively for another 24 h. The effects on HepG2 steatosis were observed
      directly under optical phase microscopy, or through oil red O staining and Nile
      red assays. In addition, the levels of reactive oxygen species (ROS) in the
      steatotic HepG2 cells with and without high-dose protopanaxadiol treatment were
      measured using fluorescent dye 2',7'-dichlorodihydrofluorescein diacetate
      staining. RESULTS: No obvious cytotoxicity was observed in the HepG2 cells
      incubated with each of the five components at up to 500 MUmol/L. At 24 h after
      incubation with FFAs, the HepG2 cells swelled and many lipid droplets
      accumulated. The lipid content was attenuated after 24 h of incubation with
      protopanaxadiol, tanshinone IIA, and emodin at 500 or 50 MUmol/L (P < 0.05),
      especially with 500 MUmol/L protopanaxadiol (P < 0.01). In addition, the ROS
      level was elevated in steatotic cells, but decreased after intervention with 500
      MUmol/L protopanaxadiol (P < 0.05). CONCLUSION: Protopanaxadiol, tanshinone IIA,
      and emodin alleviate hepatocellular steatosis in a dose-dependent manner, and
      oxidative stress regulation may partially contribute to the effects of
      protopanaxadiol.

PMID- 23867245
TI  - Antineoplastic effects of deoxyelephantopin, a sesquiterpene lactone from
      Elephantopus scaber, on lung adenocarcinoma (A549) cells.
AB  - OBJECTIVE: Deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber,
      showed inhibition of the growth of various tumor cells in vitro. In the present
      study, we investigated the cytotoxicity and apoptosis-inducing capacity of
      deoxyelephantopin on lung adenocarcinoma (A549) cells. METHODS: The cytotoxic
      effect of deoxyelephantopin on A549 cells and normal lymphocytes was evaluated
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
      and 50% inhibitory concentration (IC50) value was determined. The self-renewal
      and proliferating potential of A549 cells after treatment with deoxyelephantopin
      were examined by colony formation assay. Cellular morphology of deoxyelephantopin
      treated cells was observed using phase-contrast microscopy. The induction of
      apoptosis was evaluated using acridine orange and ethidium bromide staining,
      Hoechst 33342 staining, terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end-labeling (TUNEL) assay, DNA fragmentation analysis and Annexin V
      fluorescein isothiocyanate staining by flow cytometry. Activation of caspases was
      detected using fluorogenic substrate specific to caspases 2, 3, 8 and 9 and flow
      cytometric analysis. The total cellular DNA content and expression of cleaved
      poly (ADP-ribose) polymerase was also analyzed. RESULTS: Deoxyelephantopin
      exhibited cytotoxicity to A549 cells (IC50 = 12.287 MUg/mL), however, there was
      no toxicity towards normal human lymphocytes. Deoxyelephantopin suppressed the
      colony-forming ability of A549 cells in a dose-dependent manner. Acridine orange,
      ethidium bromide and Hoechst 33342 staining showed cell shrinkage, chromosomal
      condensation and nuclear fragmentation, indicating induction of apoptosis.
      Deoxyelephantopin increased apoptosis of A549 cells, as evidenced by more TUNEL
      positive cells. DNA fragmentation and Annexin V staining revealed late-stage
      apoptotic cell population. Deoxyelephantopin inhibited A549 cell growth by cell
      cycle arrest at G2/M phase and induced apoptosis through both extrinsic and
      intrinsic pathways. CONCLUSION: These results suggest that deoxyelephantopin has
      great potential as a new chemotherapeutic agent to be developed further for the
      treatment of lung cancer.

PMID- 23867246
TI  - Dialogue with Dr. Lixing Lao: from a factory electrician to an international
      scholar of Chinese medicine. Interview by Arthur Yin Fan.

PMID- 23867247
TI  - Evaluation on the efficacy and safety of Chinese herbal medication Xifeng
      Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter,
      open-label, randomized active-controlled trial.
AB  - BACKGROUND: Parkinson's disease (PD) is a complicated disease, commonly diagnosed
      among the elderly, which leads to degeneration of the central nervous system. It
      presently lacks an effective therapy for its complex pathogenesis. Adverse
      effects from Western drug-based medical intervention prevent long-term adherence
      to these therapies in many patients. Traditional Chinese medicine (TCM) has long
      been used to improve the treatment of PD by alleviating the toxic and adverse
      effects of Western drug-based intervention. Therefore, the aim of this study is
      to evaluate the efficacy and safety of Xifeng Dingchan Pill (XFDCP), a compound
      traditional Chinese herbal medicine, taken in conjunction with Western medicine
      in the treatment of PD patients at different stages in the progression of the
      disease. METHODS AND DESIGN: This is a multicenter, randomized controlled trial.
      In total, 320 patients with early- (n = 160) and middle-stage PD (n = 160) will
      be enrolled and divided evenly into control and trial groups. Of the 160 patients
      with early-stage PD, the trial group (n = 80) will be given XFDCP, and the
      control group (n = 80) will be given Madopar. Of the 160 patients with middle
      stage PD, the trial group (n = 80) will be given XFDCP combined with Madopar and
      Piribedil, and the control group (n = 80) will be given Madopar and Piribedil.
      The Unified Parkinson's Disease Rating Scale scores, TCM symptoms scores, quality
      of life, change of Madopar's dosage and the toxic and adverse effects of Madopar
      will be observed during a 3-month treatment period and through a further 6-month
      follow-up period. DISCUSSION: It is hypothesized that XFDCP, combined with
      Madopar and Piribedil, will have beneficial effects on patients with PD. The
      results of this study will provide evidence for developing a comprehensive
      therapy regimen, which can delay the progress of the disease and improve the
      quality of life for PD patients in different stages. TRIAL REGISTRATION: This
      trial has been registered in the Chinese Clinical Trial Registry with the
      identifer ChiCTR-TRC-12002150.

PMID- 23867248
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      diseases in External Medicine (Part 3).

PMID- 23867249
TI  - E-probe Diagnostic Nucleic acid Analysis (EDNA): a theoretical approach for
      handling of next generation sequencing data for diagnostics.
AB  - Plant biosecurity requires rapid identification of pathogenic organisms. While
      there are many pathogen-specific diagnostic assays, the ability to test for large
      numbers of pathogens simultaneously is lacking. Next generation sequencing (NGS)
      allows one to detect all organisms within a given sample, but has computational
      limitations during assembly and similarity searching of sequence data which
      extend the time needed to make a diagnostic decision. To minimize the amount of
      bioinformatic processing time needed, unique pathogen-specific sequences (termed
      e-probes) were designed to be used in searches of unassembled, non-quality
      checked, sequence data. E-probes have been designed and tested for several
      selected phytopathogens, including an RNA virus, a DNA virus, bacteria, fungi,
      and an oomycete, illustrating the ability to detect several diverse plant
      pathogens. E-probes of 80 or more nucleotides in length provided satisfactory
      levels of precision (75%). The number of e-probes designed for each pathogen
      varied with the genome size of the pathogen. To give confidence to diagnostic
      calls, a statistical method of determining the presence of a given pathogen was
      developed, in which target e-probe signals (detection signal) are compared to
      signals generated by a decoy set of e-probes (background signal). The E-probe
      Diagnostic Nucleic acid Analysis (EDNA) process provides the framework for a new
      sequence-based detection system that eliminates the need for assembly of NGS
      data. 

PMID- 23867250
TI  - Burkholderia pseudomultivorans sp. nov., a novel Burkholderia cepacia complex
      species from human respiratory samples and the rhizosphere.
AB  - Eleven Burkholderia cepacia-like isolates of human clinical and environmental
      origin were examined by a polyphasic approach including recA and 16S rRNA
      sequence analysis, multilocus sequence analysis (MLSA), DNA base content
      determination, fatty acid methyl ester analysis, and biochemical
      characterization. The results of this study demonstrate that these isolates
      represent a novel species within the B. cepacia complex (Bcc) for which we
      propose the name Burkholderia pseudomultivorans. The type strain is strain LMG
      26883(T) (=CCUG 62895(T)). B. pseudomultivorans can be differentiated from other
      Bcc species by recA gene sequence analysis, MLSA, and several biochemical tests
      including growth at 42 degrees C, acidification of sucrose and adonitol, lysine
      decarboxylase and beta-galactosidase activity, and esculin hydrolysis. 

PMID- 23867251
TI  - SC-535, a novel oral multikinase inhibitor, showed potent antitumor activity in
      human melanoma models.
AB  - BACKGROUND: Melanoma is considered as one of the most aggressive and deadliest
      cancers and current targeted therapies of melanoma often suffer limited efficacy
      or drug resistance. Discovery of novel multikinase inhibitors as anti-melanoma
      drug candidates is still needed. METHODS: In this investigation, we assessed the
      in vitro and in vivo anti-melanoma activities of SC-535, which is a novel small
      molecule multikinase inhibitor discovered by us recently. We analyzed inhibitory
      effects of SC-535 on various melanoma cell lines and human umbilical vascular
      endothelial cells (HUVEC) in vitro. Tumor xenografts in athymic mice were used to
      examine the in vivo activity of SC-535. RESULTS: SC-535 could efficiently inhibit
      vascular endothelial growth factor receptor (VEGFR) 1/2/3, B-RAF, and C-RAF
      kinases. It showed significant antiangiogenic potencies both in vitro and in vivo
      and considerable anti-proliferative ability against several melanoma cell lines.
      Oral administration of SC-535 resulted in dose-dependent suppression of tumor
      growth in WM2664 and C32 xenograft mouse models. Studies of mechanisms of action
      indicated that SC-535 suppressed the tumor angiogenesis and induced G2/M phase
      cell cycle arrest in human melanoma cells. SC-535 possesses favorable
      pharmacokinetic properties. CONCLUSION: All of these results support SC-535 as a
      potential candidate for clinical studies in patients with melanoma.

PMID- 23867253
TI  - Evaluation of factors related to late recurrence--later than 10 years after the
      initial treatment--in primary breast cancer.
AB  - BACKGROUND: Breast cancer is associated with a relatively good prognosis.
      Prognostic factors examined to date are related to early recurrence while those
      related to late recurrence and their countermeasures remain unclear. Therefore,
      we examined the factors related to late recurrence. PATIENTS AND METHODS: From
      January 1980 to August 2012, 4,774 patients who underwent primary treatment and
      estrogen (ER) and progesterone receptor (PgR) assessment were enrolled in this
      study. The patients were divided into two groups, those with a follow-up period
      <10 years and those without any recurrence at 10 years but who continued follow
      up examinations. Recurrence occurred in 711 patients followed up for <10 years
      and in 51 patients for >=10 years. RESULTS: The overall 10-year cumulative
      disease-free survival rate was 79.5%, and the recurrence rate at >=10 years was
      5.8%. A multivariate analysis revealed that the factors related to late
      recurrence were PgR positivity and positive nodes. This result differed from that
      for early recurrence in terms of ER/PgR, Ki-67 index and p53 overexpression.
      CONCLUSION: PgR positivity and lymph node metastases significantly correlated
      with late recurrence. Therefore, it is important to evaluate appropriate measures
      such as treatment period and treatment regimen for hormone-sensitive patients.

PMID- 23867252
TI  - Posttranslational modification and conformational state of heat shock protein 90
      differentially affect binding of chemically diverse small molecule inhibitors.
AB  - Heat shock protein 90 (Hsp90) is an essential molecular chaperone in eukaryotes
      that facilitates the conformational maturation and function of a diverse protein
      clientele, including aberrant and/or over-expressed proteins that are involved in
      cancer growth and survival. A role for Hsp90 in supporting the protein
      homeostasis of cancer cells has buoyed interest in the utility of Hsp90
      inhibitors as anti-cancer drugs. Despite the fact that all clinically evaluated
      Hsp90 inhibitors target an identical nucleotide-binding pocket in the N domain of
      the chaperone, the precise determinants that affect drug binding in the cellular
      environment remain unclear, and it is possible that chemically distinct
      inhibitors may not share similar binding preferences. Here we demonstrate that
      two chemically unrelated Hsp90 inhibitors, the benzoquinone ansamycin
      geldanamycin and the purine analog PU-H71, select for overlapping but not
      identical subpopulations of total cellular Hsp90, even though both inhibitors
      bind to an amino terminal nucleotide pocket and prevent N domain dimerization.
      Our data also suggest that PU-H71 is able to access a broader range of N domain
      undimerized Hsp90 conformations than is geldanamycin and is less affected by
      Hsp90 phosphorylation, consistent with its broader and more potent anti-tumor
      activity. A more complete understanding of the impact of the cellular milieu on
      small molecule inhibitor binding to Hsp90 should facilitate their more effective
      use in the clinic. 

PMID- 23867254
TI  - Comparison and validation of finite element analysis with a servo-hydraulic
      testing unit for a biodegradable fixation system in a rabbit model.
AB  - The aim of this study was the biomechanical validation of three-dimensional
      finite element analysis (FEA) with a servo-hydraulic testing unit (STU) for a
      resorbable fixation system (RFS) in a rabbit model. Bilateral mandibular vertical
      body osteotomies (BMVBO) were performed in 15 female New Zealand rabbits. The
      animals were divided into three groups. The STU and FEA tests were done
      immediately after surgery in group 1 (1 day), at the first postoperative month in
      group 2, and at the third postoperative month in group 3. Both stress tests were
      carried out by applying vertical forces at the lower incisal edge, loading from 0
      N force and increasing this until breakage occurred at the bone. The maximum
      forces that the hemimandibles could stand and the amount of deformation were
      recorded and analysed with the FEA and STU tests. We found the STU and FEA test
      results to be similar and that they could be used interchangeably for groups 1
      and 3. However, the FEA results differed most from the real STU values in group 2
      because of callus formation that had not ossified at the osteotomy line.

PMID- 23867255
TI  - Maxillary quadrangular Le Fort I osteotomy: long-term skeletal stability and
      clinical outcome.
AB  - The primary purpose of this study was to evaluate the long-term skeletal
      stability of the maxillary quadrangular Le Fort I osteotomy, and secondarily to
      determine patient overall experience and satisfaction with the surgical outcome.
      This retrospective cohort study evaluated a sample of patients with midface
      zygomatic-maxillary deficiency and Class III skeletal malocclusion. The primary
      outcome measure, on the basis of cephalometric analysis, was long-term vertical
      and horizontal skeletal stability in cleft and non-cleft patients, with and
      without interpositional autogenous iliac bone graft stabilization. A
      questionnaire measured patient overall experience and satisfaction with the
      surgery. One hundred twenty-one patients completed the questionnaire. Of these,
      53 satisfied the cephalometric study inclusion criteria. Horizontal and vertical
      intraoperative movement and late postoperative movement showed overall high
      skeletal stability. No statistical difference in horizontal skeletal stability
      was noted between cleft and non-cleft patients, or between patients receiving or
      not receiving a bone graft. Mean satisfaction with the overall treatment result
      was 9.2 of 10 (10 being highest satisfaction). We conclude that the quadrangular
      Le Fort I osteotomy is a functionally stable and surgically predictable procedure
      for cleft and non-cleft patients with or without interpositional iliac bone
      graft, with a midfacial zygomatic-maxillary deficiency. 

PMID- 23867256
TI  - Evaluation of bioresorbable plates in condylar fracture fixation: a case series.
AB  - The objective of this study was to evaluate the efficacy and stability of
      bioresorbable plates in condylar fractures in adults. Twelve adult patients who
      had sustained a condylar fracture, either alone or in combination with other
      mandibular fractures, were clinically and radiologically assessed for the
      efficacy and stability of bioresorbable plate and screw fixation.
      Intraoperatively, a total of seven screw breakages were noted. Six cases showed
      instability of the fractured fragments after fixation with bioresorbable plates
      and screws; the other six cases showed adequate stability. A single bioresorbable
      plate does not provide satisfactory stability for condylar fractures. Also, the
      screw breakages add additional surgical time and cost to the patient. 

PMID- 23867257
TI  - Validity of three-dimensional computed tomography measurements for Le Fort I
      osteotomy.
AB  - The purpose of this study was to test the precision and accuracy of three
      dimensional (3D) linear measurements for Le Fort I osteotomy, obtained from multi
      slice computed tomography (MSCT) and cone beam computed tomography (CBCT) scans.
      The study population consisted of 11 dried skulls submitted to 64-row MSCT and
      CBCT scans. Three-dimensional reconstructed images (3D-CT) were generated, and
      linear measurements (n=11) based on anatomical structures and landmarks of
      interest for Le Fort I osteotomy were performed independently by two oral and
      maxillofacial radiologists, twice each, using Vitrea software; this allows true
      3D measurement on 3D-CT images. The results demonstrated no statistically
      significant differences between the inter-examiner and intra-examiner analyses,
      and physical and true 3D linear measurements using MSCT and CBCT images.
      Regarding examiner accuracy, no statistically significant differences were found
      for the comparisons among the physical and the MSCT and the CBCT linear
      measurements by either examiner. For examiners 1 and 2, the analysis intra
      examiner correlation coefficient ranged from 0.87 to 0.96 and 0.82 to 0.98,
      respectively, using MSCT, and from 0.84 to 0.98 and 0.80 to 0.98, respectively,
      using CBCT, indicating almost perfect agreement for all analyses performed. 3D
      linear measurements obtained from MSCT and CBCT images were considered precise
      and accurate for Le Fort I osteotomy and thus accurate and helpful for Le Fort I
      osteotomy planning. 

PMID- 23867259
TI  - TRUC or the need for a new microbial classification.
AB  - Microbes were defined in the 19th century by L. Pasteur. Prokaryotes and
      eukaryotes, which are divided into two worlds of microbes, were introduced by E.
      Chatton in 1925. R. Woese divided this world into three domains based on
      ribosomal analysis (Bacteria, Archaea, and Eukarya). The discovery of Mimivirus
      and other Megavirales, that are microbes, led to divide the microbiological world
      into four branches. I introduced the name TRUC (Things Resisting Uncompleted
      Classifications) to accommodate the division in four of the currently known
      microbiological world.

PMID- 23867258
TI  - Risk of severe driver injury by driving with psychoactive substances.
AB  - Driving with alcohol and other psychoactive substances imposes an increased risk
      of severe injury accidents. In a population-based case-control design, the
      relative risks of severe driver injury (MAIS>=2) by driving with ten substance
      groups were approximated by odds ratios (alcohol, amphetamines, benzoylecgonine,
      cocaine, cannabis, illicit opiates, benzodiazepines and Z-drugs, i.e. zolpidem
      and zopiclone, medicinal opioids, alcohol-drug combinations and drug-drug
      combinations). Data from six countries were included in the study: Belgium,
      Denmark, Finland, Italy, Lithuania and the Netherlands. Case samples (N=2490)
      were collected from severely injured drivers of passenger cars or vans in
      selected hospitals in various regions of the countries. Control samples
      (N=15,832) were sampled in a uniform sampling scheme stratified according to
      country, time, road type and season. Relative risks were approximated by odds
      ratios and calculated by logistic regression. The estimates were adjusted for
      age, gender and country. The highest risk of the driver being severely injured
      was associated with driving positive for high concentrations of alcohol (>=0.8
      g/L), alone or in combination with other psychoactive substances. For alcohol,
      risk increased exponentially with blood alcohol concentration (BAC). The second
      most risky category contained various drug-drug combinations, amphetamines and
      medicinal opioids. Medium increased risk was associated with medium sized BACs
      (at or above 0.5 g/L, below 0.8 g/L) and benzoylecgonine. The least risky drug
      seemed to be cannabis and benzodiazepines and Z-drugs. For male drivers, the risk
      of being severely injured by driving with any of the psychoactive substances was
      about 65% of that of female drivers. For each of the substance groups there was a
      decrease in the risk of severe driver injury with increasing age. It is concluded
      that among psychoactive substances alcohol still poses the largest problem in
      terms of driver risk of getting injured.

PMID- 23867260
TI  - External validation of the international mission for prognosis and analysis of
      clinical trials model and the role of markers of coagulation.
AB  - BACKGROUND: Markers of coagulation have shown to have important value in
      predicting traumatic brain injury outcome. OBJECTIVE: To externally validate and
      investigate the role of markers of coagulation for outcome prediction by using
      the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT)
      model while adjusting for overall injury severity. METHODS: A retrospective chart
      analysis of traumatic brain injury patients admitted to Helsinki University
      Central Hospital between 2009 and 2010 was performed. Outcome was estimated by
      using the criteria of the IMPACT model. Admission international normalized ratio
      (INR) and platelet count were used as markers of coagulation. Overall injury
      severity was categorized with the injury severity score (ISS). Variables were
      added to the calculated IMPACT risk, generating new models. Model performance was
      assessed by analyzing and comparing the area under the curve (AUC) of the models.
      RESULTS: For 342 included patients, 6-month mortality was 32% and unfavorable
      neurological outcome was 36%. Patients with a poor outcome had lower platelets
      and higher INR and ISS than those with good outcome (P < .001). The IMPACT model
      had an AUC of 0.85 for predicting mortality and 0.81 for neurological outcome.
      Addition of INR but not ISS or platelets to the IMPACT predicted risk improved
      the predictive validity for mortality ([INCREMENT]AUC 0.02, P = .034) but not
      neurological outcome ([INCREMENT]AUC 0.00, P = .401). In multivariate analysis,
      INR remained significant for mortality but not for neurological outcome when
      adjusting for IMPACT risk and ISS (P = .012). CONCLUSION: The IMPACT model showed
      excellent performance, and INR was an independent predictor for mortality,
      independent of overall injury severity.

PMID- 23867261
TI  - Journal club: Spine patient outcomes research trial: do outcomes vary across
      centers for surgery for lumbar disc herniation?

PMID- 23867264
TI  - Preliminary results of the ARUBA study.

PMID- 23867267
TI  - A computational model of neuronal spiking and cognitive tasks.

PMID- 23867268
TI  - Unruptured intracranial aneurysms: risk factors and their interactions.

PMID- 23867269
TI  - Intravenous lidocaine for spine surgery pain control.

PMID- 23867270
TI  - CLARITY--a clearer view of the brain.

PMID- 23867271
TI  - Neural stem cell-mediated enzyme/prodrug therapy for glioma.

PMID- 23867272
TI  - Pericytes as a therapeutic target in scar formation after spinal cord injury.

PMID- 23867273
TI  - The present and future roles of 7Tesla MRI in cerebrovascular diseases.

PMID- 23867274
TI  - Identification of novel therapeutic targets through genomic analysis of
      meningiomas.

PMID- 23867275
TI  - Can pain be measured objectively?

PMID- 23867276
TI  - Mapping the spatial neighborhood of the regulatory 6S RNA bound to Escherichia
      coli RNA polymerase holoenzyme.
AB  - Bacterial 6S RNA interacts specifically with RNA polymerase acting as
      transcriptional regulator. Until now, no detailed characterization of the spatial
      arrangement of the non-coding RNA within the three-dimensional structure of RNA
      polymerase has been performed. Here we present results obtained with the chemical
      nuclease FeBABE tethered to distinct positions of RNA polymerase sigma(70)
      subunit. 6S RNA complexes were formed with a collection of RNA polymerases, where
      the cleavage reagent had been fused to sigma(70) single-cysteine variants close
      to regions involved in promoter recognition. FeBABE-induced cleavage sites within
      the 6S RNA structure were identified, indicating close spatial neighborhood
      between sigma(70) single-cysteine side chains and defined positions of the 6S RNA
      structure. Our analysis demonstrates close proximity between the 6S RNA internal
      hairpin and sigma(70) domain 4.2, normally involved in recognition of -35
      promoter DNA. Defined sections of the internal 6S RNA stem structure flanking the
      central bubble are positioned near conserved sigma(70) domains 3.1, 2.3 and 2.1,
      which are implicated in binding and melting DNA promoters between the -10 and -35
      elements. Moreover, we show that U44 of 6S RNA is located near RNA polymerase
      active site (sigma(70) domain 3.2), fully consistent with its function as
      starting nucleotide in RNA-directed pRNA transcription. No neighboring contacts
      were detected between 6S RNA and sigma(70) region 1.2 or between sigma(70) and
      the 6S RNA closing stem structure (residues 1-41 and 144-184). Results were used
      to dock a structural model of 6S RNA to the known three-dimensional structure of
      Escherichia coli sigma(70) RNA polymerase holoenzyme.

PMID- 23867277
TI  - An inhibitory antibody blocks the first step in the dithiol/disulfide relay
      mechanism of the enzyme QSOX1.
AB  - Quiescin sulfhydryl oxidase 1 (QSOX1) is a catalyst of disulfide bond formation
      that undergoes regulated secretion from fibroblasts and is over-produced in
      adenocarcinomas and other cancers. We have recently shown that QSOX1 is required
      for incorporation of particular laminin isoforms into the extracellular matrix
      (ECM) of cultured fibroblasts and, as a consequence, for tumor cell adhesion to
      and penetration of the ECM. The known role of laminins in integrin-mediated cell
      survival and motility suggests that controlling QSOX1 activity may provide a
      novel means of combating metastatic disease. With this motivation, we developed a
      monoclonal antibody that inhibits the activity of human QSOX1. Here, we present
      the biochemical and structural characterization of this antibody and demonstrate
      that it is a tight-binding inhibitor that blocks one of the redox-active sites in
      the enzyme, but not the site at which de novo disulfides are generated
      catalytically. Sulfhydryl oxidase activity is thus prevented without direct
      binding of the sulfhydryl oxidase domain, confirming the model for the
      interdomain QSOX1 electron transfer mechanism originally surmised based on
      mutagenesis and protein dissection. In addition, we developed a single-chain
      variant of the antibody and show that it is a potent QSOX1 inhibitor. The QSOX1
      inhibitory antibody will be a valuable tool in studying the role of ECM
      composition and architecture in cell migration, and the recombinant version may
      be further developed for potential therapeutic applications based on manipulation
      of the tumor microenvironment. 

PMID- 23867278
TI  - The effects of non-synonymous single nucleotide polymorphisms (nsSNPs) on protein
      protein interactions.
AB  - Non-synonymous single nucleotide polymorphisms (nsSNPs) are single base changes
      leading to a change to the amino acid sequence of the encoded protein. Many of
      these variants are associated with disease, so nsSNPs have been well studied,
      with studies looking at the effects of nsSNPs on individual proteins, for
      example, on stability and enzyme active sites. In recent years, the impact of
      nsSNPs upon protein-protein interactions has also been investigated, giving a
      greater insight into the mechanisms by which nsSNPs can lead to disease. In this
      review, we summarize these studies, looking at the various mechanisms by which
      nsSNPs can affect protein-protein interactions. We focus on structural changes
      that can impair interaction, changes to disorder, gain of interaction, and post
      translational modifications before looking at some examples of nsSNPs at human
      pathogen protein-protein interfaces and the analysis of nsSNPs from a network
      perspective.

PMID- 23867280
TI  - Effect of leg support on muscle cross-correlation of bilateral erector spinae
      during trunk flexion-extension performance.
AB  - Investigations corresponding to the affected factors of the cross-correlation of
      pair muscles are limited though muscle activation patterns of bilateral erector
      spinae (ES) during trunk flexion-extension performance in standing have been
      utilized as an indicator in the evaluation of low back pain condition. The
      purpose of the study is to evaluate the effect of leg support on the cross
      correlation of bilateral ES, and to test if the average of bilateral ES could
      weaken this effect. Twenty male university students volunteered for this study.
      Each performed the trunk flexion-extension in three leg support conditions
      randomly with the condition of single left leg support, double leg support and
      single right leg support, respectively. Each condition included three trials of
      trunk flexion-extension with the cycle of 5s flexion and 5s extension in
      standing. Surface electromyography from the right ES muscle as well as from the
      left one was recorded. The cross-correlation both in pair muscle of right-left ES
      and in pair muscle of right-average of bilateral ES was calculated in the flexion
      as well as extension period. A one-way ANOVA with repeated measures was used. The
      results showed that leg support has some effect on cross-correlation of bilateral
      ES, which causes the absolute value of phase lag to be significantly larger in
      flexion period. It is suggested that this effect could be weakened by the average
      of bilateral ES through significantly increasing the cross-correlation
      coefficient, and decreasing the absolute value of phase lag. 

PMID- 23867279
TI  - Distinct regions of the Escherichia coli ParC C-terminal domain are required for
      substrate discrimination by topoisomerase IV.
AB  - Type IIA DNA topoisomerases are essential enzymes that use ATP to maintain
      chromosome supercoiling and remove links between sister chromosomes. In
      Escherichia coli, the type IIA topoisomerase topo IV rapidly removes positive
      supercoils and catenanes from DNA but is significantly slower when confronted
      with negatively supercoiled substrates. The ability of topo IV to discriminate
      between positively and negatively supercoiled DNA requires the C-terminal domain
      (CTD) of one of its two subunits, ParC. To determine how the ParC CTD might
      assist with substrate discrimination, we identified potential DNA interacting
      residues on the surface of the CTD, mutated these residues, and tested their
      effect on both topo IV enzymatic activity and DNA binding by the isolated domain.
      Surprisingly, different regions of the ParC CTD do not bind DNA equivalently, nor
      contribute equally to the action of topo IV on different types of DNA substrates.
      Moreover, we find that the CTD contains an autorepressive element that inhibits
      activity on negatively supercoiled and catenated substrates, as well as a
      distinct region that aids in bending the DNA duplex that tracks through the
      enzyme's nucleolytic center. Our data demonstrate that the CTD is essential for
      proper engagement of both gate and transfer segment DNAs, reconciling different
      models to explain how topo IV discriminates between distinct DNAs topologies. 

PMID- 23867281
TI  - Vitamin D deficiency intensifies deterioration of risk factors, such as male sex
      and absence of vision, leading to increased postural body sway.
AB  - INTRODUCTION: Due to inconsistent findings, the influence of vitamin D on
      postural body sway (PBS) is currently under debate. This study evaluated the
      impact of vitamin D on PBS with regards to different foot positions and eye
      opening states in community-dwelling older individuals. METHODS: In a cross
      sectional study, we assessed PBS in 342 older individuals (264 females [average
      age (+/- SD): 68.3 +/- 9.0 years], 78 males [65.7 +/- 9.6 years]). A detailed
      medical history and vitamin D level were obtained for each individual. Fall risk
      was evaluated using the New York-Presbyterian Fall Risk Assessment Tool (NY
      PFRA). PBS parameters (area, distance, velocity, frequency) were evaluated on a
      pressure plate with feet in closed stance (CS) or hip-width stance (HWS), open
      eyes and closed eyes. Statistical analysis included logarithmic mixed models for
      repeated measures with the MIXED model procedure to test the influence of vitamin
      D (categorized in <10 MUg/l, 10-20 MUg/l, 21-30 MUg/l, >30 MUg/l), foot position,
      eye opening state, age, sex and frequency of physical activity on PBS. RESULTS:
      Vitamin D was not an independent risk factor for falls experienced in the last 12
      months. Nonetheless, PBS was higher in patients with vitamin D deficiency (<10
      MUg/l) in HWS (A/P p=0.028 and area p=0.037). Additionally, vitamin D deficiency
      intensified the deleterious effects of male sex (distance p=0.002) and absence of
      vision (area p<0.001) on PBS. CONCLUSION: Independent risk factors for increased
      PBS like male sex and absence of vision are additionally compromised by vitamin D
      deficiency.

PMID- 23867282
TI  - Automatic knee cartilage segmentation from multi-contrast MR images using support
      vector machine classification with spatial dependencies.
AB  - Accurate segmentation of knee cartilage is required to obtain quantitative
      cartilage measurements, which is crucial for the assessment of knee pathology
      caused by musculoskeletal diseases or sudden injuries. This paper presents an
      automatic knee cartilage segmentation technique which exploits a rich set of
      image features from multi-contrast magnetic resonance (MR) images and the spatial
      dependencies between neighbouring voxels. The image features and the spatial
      dependencies are modelled into a support vector machine (SVM)-based association
      potential and a discriminative random field (DRF)-based interaction potential.
      Subsequently, both potentials are incorporated into an inference graphical model
      such that the knee cartilage segmentation is cast into an optimal labelling
      problem which can be efficiently solved by loopy belief propagation. The
      effectiveness of the proposed technique is validated on a database of multi
      contrast MR images. The experimental results show that using diverse forms of
      image and anatomical structure information as the features are helpful in
      improving the segmentation, and the joint SVM-DRF model is superior to the
      classification models based solely on DRF or SVM in terms of accuracy when the
      same features are used. The developed segmentation technique achieves good
      performance compared with gold standard segmentations and obtained higher average
      DSC values than the state-of-the-art automatic cartilage segmentation studies. 

PMID- 23867283
TI  - Effectiveness of a structured curriculum focused on recognition and response to
      acute patient deterioration in an undergraduate BSN program.
AB  - The study purpose was to evaluate the effectiveness of a structured education
      curriculum with simulation training in educating undergraduate Baccalaureate of
      Science in Nursing (BSN) students to recognize and respond to patients
      experiencing acute deterioration as first responders. Researchers have
      demonstrated a lack of adequate clinical reasoning skills in new graduate nurses
      is a factor in critical patient incidents. A mixed methods design using a quasi
      experimental, repeated measures and a descriptive, qualitative approach was used.
      A convenience sample of 48 BSN students was recruited. Statistically significant
      increases were shown in knowledge, self-confidence, and perceptions of teamwork.
      Six categories emerged from the qualitative data analysis: sources of knowledge,
      knowledge as a person, knowledge as a group, reasoning under pressure, feelings,
      real person versus simulation, and values. Nursing educators need to use
      innovative teaching strategies to ameliorate or even eliminate the theory
      practice gap in nursing. 

PMID- 23867284
TI  - Implementing service improvement projects within pre-registration nursing
      education: a multi-method case study evaluation.
AB  - BACKGROUND: Preparing healthcare students for quality and service improvement is
      important internationally. A United Kingdom (UK) initiative aims to embed service
      improvement in pre-registration education. A UK university implemented service
      improvement teaching for all nursing students. In addition, the degree pathway
      students conducted service improvement projects as the basis for their
      dissertations. AIM: The study aimed to evaluate the implementation of service
      improvement projects within a pre-registration nursing curriculum. METHOD: A
      multi-method case study was conducted, using student questionnaires, focus groups
      with students and academic staff, and observation of action learning sets.
      Questionnaire data were analysed using SPSS v19. Qualitative data were analysed
      using Ritchie and Spencer's (1994) Framework Approach. RESULTS: Students were
      very positive about service improvement. The degree students, who conducted
      service improvement projects in practice, felt more knowledgeable than advanced
      diploma students. Selecting the project focus was a key issue and students
      encountered some challenges in practice. Support for student service improvement
      projects came from action learning sets, placement staff, and academic staff.
      CONCLUSION: Service improvement projects had a positive effect on students'
      learning. An effective partnership between the university and partner healthcare
      organisations, and support for students in practice, is essential.

PMID- 23867285
TI  - GSH-mediated photoactivity of pheophorbide a-conjugated heparin/gold nanoparticle
      for photodynamic therapy.
AB  - In this study, we developed a new photosensitizer (PS)-conjugated hybrid
      nanoparticle comprised of gold nanoparticle (AuNP) as an efficient energy
      quencher, polysaccharide heparin and a second generation PS, pheophorbide a (PhA)
      for PDT. The hybrid nanoparticles (PhA-H/AuNPs) with an average size of 40nm were
      prepared by surface coating of AuNPs with PhA conjugated heparins via gold-thiol
      interaction. The glutathione (GSH)-mediated switchable photoactivity of the PhA
      H/AuNPs was observed by fluorescence quenching and dequenching behaviors in the
      absence and presence of GSH. The photoactivity was significantly suppressed in
      aqueous media, but instantaneously restored at the GSH-rich intracellular
      environment to generate a strong fluorescence signal together with active
      production of singlet oxygen species with light treatment. In vitro cell tests
      revealed marked phototoxicity and high intracellular uptake of PhA-H/AuNPs in
      contrast with free PhA. The PhA-H/AuNPs also exhibited a prolonged circulation
      characteristic, enhanced tumor specificity, and improved photodynamic therapeutic
      efficacy compared with free PhA in tumor-bearing mice. As a result, the PhA
      H/AuNPs may serve as an effective smart nanomedicine platform for PDT and have
      great potential for the clinical treatment of various tumors. 

PMID- 23867286
TI  - Designing personalised cancer treatments.
AB  - The concept of personalised medicine for cancer is not new. It arguably began
      with the attempts by Salmon and Hamburger to produce a viable cellular
      chemosensitivity assay in the 1970s, and continues to this day. While clonogenic
      assays soon fell out of favour due to their high failure rate, other cellular
      assays fared better and although they have not entered widespread clinical
      practice, they have proved to be very useful research tools. For instance, the
      ATP-based chemosensitivity assay was developed in the early 1990s and is highly
      standardised. It has proved useful for evaluating new drugs and combinations, and
      in recent years has been used to understand the molecular basis of drug
      resistance and sensitivity to anti-cancer drugs. Recent developments allow
      unparalleled genotyping and phenotyping of tumours, providing a plethora of
      targets for the development of new cancer treatments. However, validation of such
      targets and new agents to permit translation to the clinic remains difficult.
      There has been one major disappointment in that cell lines, though useful, do not
      often reflect the behaviour of their parent cancers with sufficient fidelity to
      be useful. Low passage cell lines - either in culture or xenografts are being
      used to overcome some of these issues, but have several problems of their own.
      Primary cell culture remains useful, but large tumours are likely to receive neo
      adjuvant treatment before removal and that limits the tumour types that can be
      studied. The development of new treatments remains difficult and prediction of
      the clinical efficacy of new treatments from pre-clinical data is as hard as
      ever. One lesson has certainly been that one cannot buck the biology - and that
      understanding the genome alone is not sufficient to guarantee success. Nowhere
      has this been more evident than in the development of EGFR inhibitors. Despite
      overexpression of EGFR by many tumour types, only those with activating EGFR
      mutations and an inability to circumvent EGFR blockade have proved susceptible to
      treatment. The challenge is how to use advanced molecular understanding with
      limited cellular assay information to improve both drug development and the
      design of companion diagnostics to guide their use. This has the capacity to
      remove much of the guesswork from the process and should improve success rates. 

PMID- 23867287
TI  - Quantification of magnetic nanoparticles with low frequency magnetic fields:
      compensating for relaxation effects.
AB  - Quantifying the number of nanoparticles present in tissue is central to many in
      vivo and in vitro applications. Magnetic nanoparticles can be detected with high
      sensitivity both in vivo and in vitro using the harmonics of their magnetization
      produced in a sinusoidal magnetic field. However, relaxation effects damp the
      magnetic harmonics rendering them of limited use in quantification. We show that
      an accurate measure of the number of nanoparticles can be made by correcting for
      relaxation effects. Correction for relaxation reduced errors of 50% for larger
      nanoparticles in high relaxation environments to 2%. The result is a method of
      nanoparticle quantification suitable for in vivo and in vitro applications
      including histopathology assays, quantitative imaging, drug delivery and thermal
      therapy preparation. 

PMID- 23867288
TI  - Detailed modulation of phenotypes and functions of bone marrow dendritic cells
      (BMDCs) by interferon-gamma (IFN-gamma).
AB  - IFN-gamma is a cytokine that plays crucial role in innate and adaptive immunity
      against viral and intracellular bacterial infections and for tumor control. IFN
      gamma is also a key activator of macrophages [1,2]. In the present study, we
      studied detailed modulation of IFN-gamma on phenotypic and functional maturation
      of murine bone marrow derived dendritic cells (BMDCs). Phenotypic and functional
      maturation of BMDCs was evaluated by light microscope, flow cytometry(FCM),
      transmission electron microscopy (TEM), cytochemistry method, acid phosphatase
      activity(ACP), FITC-dextran bio-assay and enzyme linked immunosorbent assay
      (ELISA). We elucidated that IFN-gamma up-regulated the expression of MHC II,
      CD40, CD80, CD83 and CD86 molecules on BMDCs, down-regulated the activity of
      pinocytosis and phagocytosis by BMDCs, and induced higher levels of IL-12 and TNF
      alpha secreted by BMDCs. It is therefore confirmed that IFN-gamma can effectively
      promote the maturation of BMDCs. Our study provides more evidence and rationale
      on future application of IFN-gamma for enhancing host immunity. 

PMID- 23867289
TI  - Cytokine mediated immune responses in the Japanese pufferfish (Takifugu rubripes)
      administered with heat-killed Lactobacillus paracasei spp. paracasei (06TCa22)
      isolated from the Mongolian dairy product.
AB  - The important role played by cytokines in host innate immunity and the
      interaction of subsets of immune and inflammatory cells through cytokines offer
      avenues for immune interventions. We investigated 16 cytokine gene responses in
      the Japanese pufferfish, Takifugu rubripes orally treated with a heat-killed
      lactic acid bacterium (LAB), Lactobacillus paracasei spp. paracasei (strain
      06TCa22) (Lpp) isolated from a Mongolian dairy product at 1mgg(-1)body weightd(
      1) for 3days. Additionally, we assessed superoxide anion production (SAP) and
      phagocytic activity (PA) of head kidney cells and resistance to Vibrio harveyi
      infection in treated fish. Significant up-regulation of pro-inflammatory (IL
      1beta, IL-6, IL-17A/F-3, TNF-alpha and TNF-N), cell-mediated immunity inducing
      (IL-12p35, IL-12p40 and IL-18), antiviral/intra-cellular pathogen killing (I-IFN
      1 and IFN-gamma), anti-inflammatory (IL-10) and peripheral T cell expansion and
      survival controlling (IL-2, IL-7, IL-15, IL-21 and TGF-beta1) cytokines was
      observed in the treated fish. Furthermore, significantly increased SAP, PA and
      pathogen resistance were observed in the treated fish compared to untreated fish.
      Our results indicate the enhancement of cytokine mediated immunity in T. rubripes
      by the use of the heat-killed Lpp as a potential immunostimulant and would be of
      great use in immunomodulation trials with the possibility to monitor positive
      immune response. 

PMID- 23867290
TI  - Induction of pro-inflammatory cytokine production in thymocytes by the immune
      response modifiers Imiquimod and GardiquimodTM.
AB  - An emerging role is postulated for IL-17-producing thymocytes, which in their
      majority consist of IL-17-producing CD4(+) cells. For these, a specific role in
      the immediate defense against infectious pathogens is suggested, independent from
      the development of an adaptive immune response in the immune periphery. Immune
      response modifiers, like the TLR7 ligands Imiquimod and GardiquimodTM are
      effective pharmacological therapeutics applied topically against dermal tumors
      and virus infections and have been demonstrated to activate immune cells. In this
      study, we investigated the effect of Imiquimod and GardiquimodTM on murine
      thymocyte cytokine production with a particular focus on IL-17. We find that both
      substances dose-dependently are able to trigger IFN-gamma and IL-6 production,
      but no IL-17 production. Moreover, a strong co-stimulating effect is detected on
      alpha-CD3-induced IFN-gamma, IL-6 and IL-17 production. We conclude that
      Imiquimod and GardiquimodTM are not only modifiers of the adaptive immune
      response, but might also have additional therapeutic potential by modifying the
      immune activity in the thymus. 

PMID- 23867291
TI  - A comparison between rib fracture patterns in peri- and post-mortem compressive
      injury in a piglet model.
AB  - OBJECTIVES: Forensic biomechanics is increasingly being used to explain how
      observed injuries occur. We studied infant rib fractures from a biomechanical and
      morphological perspective using a porcine model. METHODS: We used 24, 6th ribs of
      one day old domestic pigs Sus scrofa, divided into three groups, desiccated
      (representing post-mortem trauma), fresh ribs with intact periosteum
      (representing peri-mortem trauma) and those stored at -20 degrees C. Two
      experiments were designed to study their biomechanical behaviour fracture
      morphology: ribs were axially compressed and subjected to four-point bending in
      an Instron 3339 fitted with custom jigs. Morphoscopic analysis of resultant
      fractures consisted of standard optical methods, micro-CT (MUCT) and Scanning
      Electron Microscopy (SEM). RESULTS: During axial compression fresh ribs did not
      fracture because of energy absorption capabilities of their soft and fluidic
      components. In flexure tests, dry ribs showed typical elastic-brittle behaviour
      with long linear load-extension curves, followed by short non-linear elastic
      (hyperelastic) behaviour and brittle fracture. Fresh ribs showed initial linear
      elastic behaviour, followed by strain softening and visco-plastic responses.
      During the course of loading, dry bone showed minimal observable damage prior to
      the onset of unstable fracture. Frozen then thawed bone showed similar patterns
      to fresh bone. Morphologically, fresh ribs showed extensive periosteal damage to
      the tensile surface with areas of collagen fibre pull-out along the tensile
      surface. While all dry ribs fractured precipitously, with associated fibre pull
      out, the latter feature was absent in thawed ribs. CONCLUSIONS: Our study
      highlights the fact that under controlled loading, fresh piglet ribs
      (representing perimortem trauma) did not fracture through bone, but was
      associated with periosteal tearing. These results suggest firstly, that complete
      lateral rib fracture in infants may in fact not result from pure compression as
      has been previously assumed; and secondly, that freezing of bone during storage
      may affect its fracture behaviour.

PMID- 23867292
TI  - Assessment of the in-plane biomechanical properties of human skin using a finite
      element model updating approach combined with an optical full-field measurement
      on a new tensile device.
AB  - Human skin is one of the most important organ of the body. The assessment and
      knowledge of its properties are very useful for clinical or cosmetic research.
      Many techniques are used to measure the mechanical properties of this organ, like
      suction, indentation, torsion or tension tests. The aim of this paper is to
      present a new device based on tension technique and combining mechanical and
      optical measurements. The whole procedure used to assess the displacement field
      as described, and first results of tests performed in vivo are shown. 

PMID- 23867293
TI  - Numerical description and experimental validation of a rheology model for non
      Newtonian fluid flow in cancellous bone.
AB  - Fluids present or used in biology, medicine and (biomedical) engineering are
      often significantly non-Newtonian. Furthermore, they are chemically complex and
      can interact with the porous matrix through which they flow. The porous
      structures themselves display complex morphological inhomogeneities on a wide
      range of length scales. In vertebroplasty, a shear-thinning fluid, e.g.
      poly(methyl methacrylate) (PMMA), is injected into the cavities of vertebral
      trabecular bone for the stabilization of fractures and metastatic lesions. The
      main objective of this study was therefore to provide a protocol for numerically
      investigating the rheological properties of PMMA-based bone cements to predict
      its spreading behavior while flowing through vertebral trabecular bone. A
      numerical upscaling scheme based on a dimensionless formulation of the Navier
      Stokes equation is proposed in order to relate the pore-scale rheological
      properties of the PMMA that were experimentally estimated using a plate
      rheometer, to the continuum-scale. On the pore length scale, a viscosity change
      on the order of one magnitude was observed whilst the shear-thinning properties
      caused a viscosity change on the order of only 10% on the continuum length scale
      and in a flow regime that is relevant for vertebroplasty. An experimental
      validation, performed on human cadaveric vertebrae (n=9), showed a significant
      improvement of the cement spreading prediction accuracy with a non-Newtonian
      formulation. A root mean square cement surface prediction error of 1.53mm
      (assuming a Newtonian fluid) and 1.37mm (assuming a shear-thinning fluid) was
      found. Our findings highlight the importance of incorporating the non-Newtonian
      fluids properties in computational models of porous media at the appropriate
      length scale. 

PMID- 23867294
TI  - Artificial hip joints: The biomaterials challenge.
AB  - What is new and what comes next in artificial hip joints? These are the crucial
      questions we attempt to answer after accurately surveying the state of the art in
      the field of hip arthroplasty, especially related to non-metallic materials.
      Summarizing the present situation, one could safely state that the current
      generation of hard-on-soft and hard-on-hard hip bearings has become quite
      effective in exhibiting extremely low degrees of wear when compared to
      traditional implants made of cobalt-chromium alloys coupled with conventional
      polyethylene materials or to the primitive alumina materials used in the past.
      Moreover, at a stage of more than 10 years in the clinical follow-up of new
      generations of hard-on-hard bearings, and more than 10 years follow-up for highly
      cross-linked polyethylene materials, we should soon be expecting a new set of
      officially compiled statistics that show significant reductions in failures due
      to particle-mediated osteolysis as compared to past statistical compilations.
      However, further important issues (other than wear) remain unsolved, including
      structural reliability of advanced ceramic and polyethylene components. Severe
      challenges yet stand in optimizing the biomaterials choice for significantly
      extended lifetimes and reduced failure risks. Moreover, joint healing trends are
      expected to evolve more radically in the next few decades. 

PMID- 23867295
TI  - Folded-chain structure of cellulose II suggested by molecular dynamics
      simulation.
AB  - We investigated the possibility of a folded-chain crystal of the cellulose II
      polymorph by molecular dynamics (MD) simulation. The molecular direction of
      cellulose chains in cellulose II is anti-parallel, which allows the crystal to
      have folded-chain packing. It is impossible for cellulose I to form such a
      structure due to its parallel up assembly. The folded-chain crystal of the
      cellulose II polymorph was suggested based on the following results: (1) the
      glucose residue with boat and skew boat ring conformations enabled the cellulose
      chain to form a hairpin turn; (2) the lattice parameters of the folded-chain
      crystal and original crystal were almost the same (deviations in the a, b, and
      gamma parameters of both crystals were within 3%); (3) the folded-chain molecular
      sheet was as stable in a water medium as the extended-chain molecular sheet, and
      structural parameters such as the hydrogen bonding system and side chain
      conformation of both molecular sheets were almost the same, indicating that the
      folded-chain molecular sheet is an initial structure during crystallization of
      the folded-chain crystal. 

PMID- 23867296
TI  - Synthesis and antioxidant activity of a novel class of fluorescein-based beta-C
      glycosides.
AB  - A series of fluorescein-based beta-C-glycosyl ketones were synthesized through
      aldol condensation of beta-C-glycosyl ketones with fluorescein monoaldehyde under
      ambient reaction conditions in good yields. Formation of the expected product has
      been confirmed through different spectral techniques. Fluorescein-based beta-C
      glycosides show moderate anti-oxidant activities with maximum inhibitory activity
      of 60%. 

PMID- 23867297
TI  - Study on polymethylmethacrylate ring in protecting limbal stem cells during
      collagen cross-linking.
AB  - OBJECTIVE: The UV rays used in the collagen cross-linking (CXL) procedure seem to
      cause potential damage to the limbal stem cells. This study was designed to
      evaluate the ability of polymethylmethacrylate (PMMA) hemiannulus as an
      alternative to protect corneal limbal stem cells during CXL. METHODS: Ten freshly
      enucleated human cadaveric eyeballs were subjected to the corneal CXL procedure.
      The cadaveric eye ball was divided into 2 sectors: A and B. Sector A was left
      unprotected, while sector B was covered by a PMMA shield. Limbal biopsies from
      both sectors before and after the procedure were analyzed. Each limbal tissue was
      placed on human amniotic membrane (HAM) to check the cultivability and was
      subjected to marker studies using reverse transcriptase PCR. RESULTS: Before CXL,
      biopsies from both sectors showed growth on HAM. After CXL, biopsies from sector
      A showed no growth on HAM while 2 out of the 10 from sector B covered with the
      PMMA ring did show growth on HAM. The putative stem-cell marker ABCG2 was
      negative in all the samples from sector A after CXL and was positive in 2 out of
      the 10 samples from sector B. CONCLUSION: Covering the limbal region with PMMA
      offers partial protection of the limbus from the UV rays during the CXL
      procedure.

PMID- 23867298
TI  - Delayed neurological deterioration after mild head injury: cause, temporal
      course, and outcomes.
AB  - BACKGROUND: Mild head injury (MHI) complicated by an intracranial hemorrhage
      (ICH) is a common cause of hospital admission after head trauma. Most patients
      are treated nonoperatively, remain neurologically stable, and are discharged
      uneventfully. However, a small percentage of patients suffer delayed neurological
      deterioration (DND). Little is known about the characteristics of DND after an
      MHI complicated by ICH. OBJECTIVE: To identify the cause, temporal course, and
      outcomes of patients who deteriorated neurologically after presenting with MHI
      and ICH. METHODS: A retrospective review was performed of all adult patients
      presenting over 54 consecutive months with MHI and ICH. Patients who were treated
      nonoperatively after initial head computed tomography and had a subsequent DND
      (Glasgow Coma Scale score decrease >=2) were identified. Demographics,
      neurological status, clinical course, radiographic findings, and outcome data
      were collected. RESULTS: Over 54 months, 757 patients with MHI plus ICH were
      admitted for observation; of these, 31 (4.1%) experienced DND. Eighty-seven
      percent of patients deteriorated within 24 hours after admission. Twenty-one
      patients (68%) deteriorated as a result of progressive intracranial hemorrhage,
      and 10 patients (32%) deteriorated as a result of medical causes. Seven patients
      (23%) died. Variables significantly associated with mortality included age > 60
      years, coagulopathy, and change in Marshall computed tomography classification.
      CONCLUSION: The incidence of delayed neurological deterioration after MHI with
      ICH is low and usually occurs within 24 hours after admission. It results in
      significant morbidity and mortality if it is the result of progressive
      intracranial hemorrhage. Further research is needed to identify risk factors that
      can allow early detection and improve outcomes in these patients.

PMID- 23867299
TI  - The clinical effects of deep brain stimulation of the pedunculopontine tegmental
      nucleus in movement disorders may not be related to the anatomical target, leads
      location, and setup of electrical stimulation.
AB  - BACKGROUND: The pedunculopontine tegmental nucleus (PPTg) is a novel target for
      deep brain stimulation (DBS) in movement disorders. OBJECTIVE: To clarify the
      relationships between the individual anatomic variations of the brainstem, the
      site in which the PPTg DBS is applied, and the clinical outcome in a relatively
      large number of patients affected by Parkinson disease or progressive
      supranuclear palsy. METHODS: Magnetic resonance images have been used to evaluate
      brainstem anatomy and the relationships between lead position and specific
      brainstem landmarks. All data were matched on atlas representations of the PPTg
      and were correlated with Unified Parkinson Disease Rating Scale III (UPDRS III),
      subitems 27 to 30 of UPDRS III and the Hoehn and Yahr evaluations. RESULTS: A
      high variance of brainstem parameters was evident, affecting the relationships
      between the position of the nucleus and lead contacts. According to the contacts
      giving the best clinical outcome, patients could be distinguished between those
      who required the use of 2 adjacent contacts and those who required stimulation
      through 2 nonadjacent contacts. Furthermore, in the former group the target
      coordinates were more lateral and deeper compared with the latter group.
      CONCLUSION: Individual PPTg-DBS planning is required to overcome the
      inconsistencies linked to the high variability in the brainstem anatomy of
      patients. The lack of correlations between lead position, contact setup, and
      clinical outcome indicate that the benefits of PPTg DBS may not be strictly
      linked to the site of stimulation within the PPTg area, and may not depend upon
      the neurons still surviving in this region in Parkinson disease or progressive
      supranuclear palsy.

PMID- 23867300
TI  - Effects of remote ischemic preconditioning on the coagulation profile of patients
      with aneurysmal subarachnoid hemorrhage: a case-control study.
AB  - BACKGROUND: Animal studies suggest that ischemic preconditioning prolongs
      coagulation times. OBJECTIVE: Because coagulation changes could hinder the
      translation of preconditioning into clinical settings where hemorrhage may be an
      issue, such as ischemic or hemorrhagic stroke, we evaluated the effects of remote
      ischemic preconditioning (RIPC) on coagulation in patients undergoing RIPC after
      aneurysmal subarachnoid hemorrhage (SAH). METHODS: Twenty-one patients with SAH
      (mean age, 56.3 years) underwent 137 RIPC sessions 2 to 12 days after SAH, each
      consisting of 3 to 4 cycles of 5 to 10 minutes of lower limb ischemia followed by
      reperfusion. Partial thromboplastin time (PTT), prothrombin time (PT), and
      international normalized ratio (INR) were analyzed before and after sessions.
      Patients were followed for hemorrhagic complications. RESULTS: No immediate
      effect was identified on PTT (mean pre-RIPC, 27.62 s; post-RIPC, 27.54 s; P =
      .82), PT (pre-RIPC, 10.77 s; post-RIPC, 10.81 s; P = .59), or INR (pre-RIPC,
      1.030; post-RIPC, 1.034; P = .57) after each session. However, statistically
      significant increases in PT and INR were identified after exposure to at least 4
      sessions (mean PT pre-RIPC, 11.33 s; post-RIPC, 12.1 s; P = .01; INR pre-RIPC,
      1.02; post-RIPC, 1.09; P = .014, PTT pre-RIPC, 27.4 s; post-RIPC, 27.85 s; P =
      .092) with a direct correlation between the number of sessions and the degree of
      increase in PT (Pearson correlation coefficient = 0.59, P = .007) and INR
      (Pearson correlation coefficient = 0.57, P = .010). Prolonged coagulation times
      were not observed in controls. No hemorrhagic complications were associated with
      the procedure. CONCLUSION: RIPC by limb ischemia appears to prolong the PT and
      INR in human subjects with SAH after at least 4 sessions, correlating with the
      number of sessions. However, values remained within normal range and there were
      no hemorrhagic complications.

PMID- 23867301
TI  - Radiosurgery for primary motor and sensory cortex arteriovenous malformations:
      outcomes and the effect of eloquent location.
AB  - BACKGROUND: Eloquent intracranial arteriovenous malformations (AVMs) located in
      the primary motor or somatosensory cortex (PMSC) carry a high risk of
      microsurgical morbidity. OBJECTIVE: To evaluate the outcomes of radiosurgery on
      PMSC AVMs and compare them with radiosurgery outcomes in a matched cohort of
      noneloquent lobar AVMs. METHODS: Between 1989 and 2009, 134 patients with PMSC
      AVMs underwent Gamma Knife radiosurgery with a median radiographic and clinical
      follow-up of 64 and 80 months, respectively. Seizure (40.3%) and hemorrhage
      (28.4%) were the most common presenting symptoms. Pre-radiosurgery embolization
      was performed in 33.6% of AVMs. Median AVM volume was 4.1 mL (range, 0.1-22.6
      mL), and prescription dose was 20 Gy (range, 7-30 Gy). Cox regression analysis
      was performed to identify factors associated with obliteration. RESULTS: The
      overall obliteration rate, including magnetic resonance imaging and angiography,
      after radiosurgery was 63%. Obliteration was achieved in 80% of AVMs with a
      volume less than 3 mL compared with 55% for AVMs larger than 3 mL. No previous
      embolization (P = .002) and a single draining vein (P = .001) were independent
      predictors of obliteration on multivariate analysis. The annual post-radiosurgery
      hemorrhage risk was 2.5%. Radiosurgery-related morbidity was temporary and
      permanent in 14% and 6% of patients, respectively. Comparing PMSC AVMs with
      matched noneloquent lobar AVMs, the obliteration rates and clinical outcomes
      after radiosurgery were not statistically different. CONCLUSION: For patients
      harboring PMSC AVMs, radiosurgery offers a reasonable chance of obliteration with
      a relatively low complication rate. Eloquent location does not appear to confer
      the same negative prognostic value for radiosurgery that it does for
      microsurgery.

PMID- 23867302
TI  - Dendritic cell vaccine for recurrent high-grade gliomas in pediatric and adult
      subjects: clinical trial protocol.
AB  - BACKGROUND: Although there have been significant advances in understanding the
      basic pathogenesis of glioblastoma multiforme, the median survival of patients
      has changed little in the past 25 years. Recent studies have suggested that
      immune modulation through dendritic cell (DC) vaccines may stimulate the immune
      system against tumor antigens and potentially increase survival. OBJECTIVE: To
      determine whether the use of adjuvant vaccination with autologous DCs (matured in
      situ after being loaded with tumor cell lysate derived from autologous refractory
      gliomas) is safe, feasible, and beneficial for adult and pediatric patients with
      recurrent high-grade gliomas. METHODS: The study design is a single-center,
      nonrandomized, open phase I clinical trial. A total of 20 patients with malignant
      gliomas will be enrolled preoperatively over 2 years. Patients will be given
      adjuvant vaccination with autologous DCs loaded with tumor lysate after maximal
      safe surgical resection. EXPECTED OUTCOMES: Using topical imiquimod before
      vaccination, it is anticipated that the immune response in vaccinated patients
      and potentially Overall survival will be greater than that demonstrated in the
      literature. We anticipate that there will be minimal side effects (minor
      dermatitis) associated with this treatment. DISCUSSION: In the current trial, we
      assess immune response, safety, and survival using a novel vaccine protocol
      developed in Belgium that seems to markedly increase survival of certain
      subjects. Nevertheless, larger randomized clinical studies need to be performed
      to evaluate fully the efficacy of this therapy for both recurrent and newly
      diagnosed glioblastoma.

PMID- 23867303
TI  - The microenvironment in classical Hodgkin lymphoma: an actively shaped and
      essential tumor component.
AB  - Classical Hodgkin lymphoma (cHL) is characterized by a minority of tumor cells
      derived from germinal center B-cells and a vast majority of non-malignant
      reactive cells. The tumor cells show a loss of B-cell phenotype including lack of
      the B-cell receptor, which makes the tumor cells vulnerable to apoptosis. To
      overcome this threat, tumor cells and their precursors depend on anti-apoptotic
      and growth stimulating factors that are obtained via triggering of multiple
      membrane receptors. In addition, tumor cells shape the environment by producing a
      wide variety of chemokines and cytokines. These factors alter the composition of
      the microenvironment and modulate the nature and effectiveness of the
      infiltrating cells. The attracted cells enhance the pro-survival and growth
      stimulating signals for the tumor cells. To escape from an effective anti-tumor
      response tumor cells avoid recognition by T and NK cells, by downregulation of
      HLA molecules and modulating NK and T-cell receptors. In addition, the tumor
      cells produce immune suppressive cytokines that inhibit cytotoxic responses. In
      this review the relevance of the microenvironment in the pathogenesis of cHL will
      be discussed. 

PMID- 23867304
TI  - Relationship between microemboli in the internal carotid artery and the
      occurrence of ischemic stroke after transient ischemic attack.
AB  - Microembolic signals (MES) have been reported to be an independent risk factor
      for stroke and transient ischemic attack (TIA). We examined the relationship
      between MES in the internal carotid artery and the occurrence of ischemic stroke
      in patients with TIA. A total of 67 patients who had a TIA were examined with
      transcranial Doppler ultrasonography to detect microemboli in the internal
      carotid artery 1, 3, and 7 days after admission, and 3 months after discharge.
      The relationship between the presence of MES and the subsequent occurrence of
      ischemic stroke was the primary outcome of interest. 35.8% (24/67) of patients
      were MES(+). During follow-up, ischemic stroke occurred significantly more
      frequently in patients who were MES(+) compared with patients who were MES(-)
      (6/24; 25.0% versus 2/43; 4.7%, p=0.021), as did TIA (11/24; 45.8% versus 4/43;
      9.3%). MES(+) status was significantly associated with the occurrence of ischemic
      stroke after adjusting for age, sex, hypertension, diabetes mellitus, and drug
      therapy (odds ratio: 8.30; 95% confidence interval: 1.37-50.42; p=0.021). The
      positive and negative predictive values of MES status for predicting ischemic
      stroke were 25.0% and 95.4%, respectively. The presence of microemboli in the
      internal carotid artery appears to be an important risk factor for the occurrence
      of ischemic stroke after TIA. The MES(+) rate in patients with transient ischemic
      attack with severe internal carotid artery stenosis is markedly higher than in
      patients without internal carotid artery stenosis.

PMID- 23867305
TI  - A novel nanoparticulate system for sustained delivery of acid-labile
      lansoprazole.
AB  - In the present study, an effort was made to develop the Eudragit RS100 based
      nanoparticulate system for sustained delivery of an acid-labile drug,
      lansoprazole (LPZ). LPZ-loaded Eudragit RS100 nanoparticles (ERSNPs) were
      prepared by oil-in-water emulsion-solvent evaporation method. The effects of
      various formulation variables such as polymer concentration, drug amount and
      solvent composition on physicochemical performance of nanoparticles and in vitro
      drug release were investigated. All nanoparticles were spherical with particle
      size 198.9 +/- 8.6-376.9 +/- 5.6 nm and zeta potential +35.1 +/- 1.7 to +40.2 +/-
      0.8 mV. The yield of nanoparticles was unaffected by change of these three
      variables. However, the drug loading and encapsulation efficiency were affected
      by polymer concentration and drug amount. On the other hand, the particle size of
      nanoparticles was significantly affected by polymer concentration and internal
      phase composition due to influence of droplet size during emulsification process.
      All nanoparticles prolonged drug release for 24h which was dominated by a
      combination of drug diffusion and polymer chain relaxation. The fastest and the
      slowest release rates were observed in C2-1002-10/0 and C8-4001-10/0,
      respectively, based on the release rate constant (k). Thus, the developed
      nanoparticles possessed a potential as a nano-carrier to sustain drug delivery
      for treatment of acid related disorders.

PMID- 23867306
TI  - Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic
      review and meta-analysis of randomized controlled trials.
AB  - PURPOSE: Increasing antimicrobial resistance has stimulated interest in
      nonantibiotic prophylaxis of recurrent urinary tract infections. We assessed the
      effectiveness, tolerability and safety of nonantibiotic prophylaxis in adults
      with recurrent urinary tract infections. MATERIALS AND METHODS: MEDLINE(r),
      EMBASETM, the Cochrane Library and reference lists of relevant reviews were
      searched to April 2013 for relevant English language citations. Two reviewers
      selected randomized controlled trials that met the predefined criteria for
      population, interventions and outcomes. The difference in the proportions of
      patients with at least 1 urinary tract infection was calculated for individual
      studies, and pooled risk ratios were calculated using random and fixed effects
      models. Adverse event rates were also extracted. The Jadad score was used to
      assess risk of bias (0 to 2-high risk and 3 to 5-low risk). RESULTS: We
      identified 5,413 records and included 17 studies with data for 2,165 patients.
      The oral immunostimulant OM-89 decreased the rate of urinary tract infection
      recurrence (4 trials, sample size 891, median Jadad score 3, RR 0.61, 95% CI 0.48
      0.78) and had a good safety profile. The vaginal vaccine Urovac(r) slightly
      reduced urinary tract infection recurrence (3 trials, sample size 220, Jadad
      score 3, RR 0.81, 95% CI 0.68-0.96) and primary immunization followed by booster
      immunization increased the time to reinfection. Vaginal estrogens showed a trend
      toward preventing urinary tract infection recurrence (2 trials, sample size 201,
      Jadad score 2.5, RR 0.42, 95% CI 0.16-1.10) but vaginal irritation occurred in 6%
      to 20% of women. Cranberries decreased urinary tract infection recurrence (2
      trials, sample size 250, Jadad score 4, RR 0.53, 95% CI 0.33-0.83) as did
      acupuncture (2 open label trials, sample size 165, Jadad score 2, RR 0.48, 95% CI
      0.29-0.79). Oral estrogens and lactobacilli prophylaxis did not decrease the rate
      of urinary tract infection recurrence. CONCLUSIONS: The evidence of the
      effectiveness of the oral immunostimulant OM-89 is promising. Although sometimes
      statistically significant, pooled findings for the other interventions should be
      considered tentative until corroborated by more research. Large head-to-head
      trials should be performed to optimally inform clinical decision making.

PMID- 23867308
TI  - Marluce Bibbo retires as editor-in-chief of Acta Cytologica.

PMID- 23867307
TI  - Sleep related problems and urological symptoms: testing the hypothesis of
      bidirectionality in a longitudinal, population based study.
AB  - PURPOSE: We evaluate the bidirectional association between urological symptoms
      (urinary incontinence, lower urinary tract symptoms and nocturia) and sleep
      related variables. MATERIALS AND METHODS: Data were obtained from a prospective
      cohort study of 1,610 men and 2,535 women who completed baseline (2002 to 2005)
      and followup (2006 to 2010) phases of the BACH (Boston Area Community Health)
      Survey, a population based random sample survey. Sleep restriction (5 hours or
      less per night), restless sleep, sleep medication use and urological symptoms
      were assessed by self-report. Urinary incontinence was defined as weekly leakage
      or moderate/severe leakage, lower urinary tract symptoms (overall, obstructive,
      irritative) were defined by the AUA-SI (American Urological Association symptom
      index) and nocturia was defined as urinary frequency 2 or more times per night.
      RESULTS: At the 5-year followup 10.0%, 8.5% and 16.0% of subjects newly reported
      lower urinary tract symptoms, urinary incontinence and nocturia, respectively,
      and 24.2%, 13.3% and 11.6% newly reported poor sleep quality, sleep restriction
      and use of sleep medication, respectively. Controlling for confounders, the odds
      of urological symptoms developing were consistently increased for subjects who
      reported poor sleep quality and sleep restriction at baseline, but only baseline
      nocturia was positively associated with incident sleep related problems at
      followup. Body mass index, a potential mediator, reduced selected associations
      between sleep and incident urinary incontinence and irritative symptoms, but C
      reactive protein did not. CONCLUSIONS: These data suggest that self-reported
      sleep related problems and urological symptoms are linked bidirectionally, and
      that body mass index may be a factor in the relationship between sleep and the
      development of urological symptoms.

PMID- 23867309
TI  - Germline counterparts of oncogenic mutations: who gives a JAK?.

PMID- 23867310
TI  - Impact of sunitinib on human thyroid cancer cells.
AB  - BACKGROUND/AIMS: Thyroid cancer accounts for about 1% of all cancer cases.
      Multikinase inhibitors like sunitinib (S) have a promising potential in thyroid
      cancer therapy. Therefore, the principal aim of this study was to investigate the
      impact of sunitinib on the secretion of cytokines of follicular thyroid cancer
      cells. METHOD: The effects of irradiation (R), S, and their combination (R+S) on
      cytokine secretion by the human thyroid cancer cell lines ML-1 and CGTH W-1 were
      evaluated after two (d2) and four days (d4) of treatment. RESULTS: Multi-Analyte
      Profiling of cytokine release showed a decrease after S treatment (CGTH W-1: IFN
      gamma, IL-4, IL-8 d2, MIP-1a, MMP-2, TNF-alpha and TNF-beta; ML-1: IFN-gamma, IL
      4, IL-6, IL-7, IL-8; MIP-1alpha, MMP-2, MCP-1, TNF-alpha and TNF-beta). R
      elevated significantly the release of cytokines (exception ML-1: MCP-1, MMP-2;
      CGTH W-1: IL-4, TNF-beta). In contrast, R+S treatment resulted in a reduction of
      IFN-gamma, IL-4, and MMP-2 in both cell lines. IL-6, IL-8 and MCP-1 proteins in
      the supernatant correlated with the data obtained by quantitative RT-PCR. VEGFD
      mRNAs were significantly elevated by R+S. CONCLUSION: A target-based therapy with
      R+S changed VEGFD, IL-6 and IL-8 in follicular thyroid cancer cells. These in
      vitro-experiments suggest IL-6, IL-8, VEGFD and TNF-alpha as interesting
      biomarkers to be investigated in vivo. Different reactions of the cell lines
      under equal treatment might be due to their different origin and characteristics.

PMID- 23867311
TI  - Does occult HBV infection have an impact on the evolution of chronic hepatitis C?

PMID- 23867312
TI  - Hepatic menin recruits SIRT1 to control liver steatosis through histone
      deacetylation.
AB  - BACKGROUND & AIMS: The development and progression of non-alcoholic fatty liver
      disease are associated with aging, obesity, and type 2 diabetes. Understanding
      the precise regulatory networks of this process will contribute to novel
      therapeutic strategies. METHODS: Hepatocyte-specific Men1 knockout mice were
      generated using Cre/loxP technology. Lipid and glucose metabolic phenotypes and
      mechanisms were investigated in aging and high-fat diet fed mice. RESULTS: The
      expression of menin, encoded by multiple endocrine neoplasia 1 (Men1) gene, is
      reduced in the liver of aging mice. Hepatocyte-specific deletion of Men1 induces
      liver steatosis in aging mice. Menin deficiency promotes high-fat diet-induced
      liver steatosis in mice. Menin recruits SIRT1 to control hepatic CD36 expression
      and triglyceride accumulation through histone deacetylation. CONCLUSIONS: Our
      work reveals that the adaptor protein menin is critical for the progression of
      hepatic steatosis during aging and metabolic imbalance.

PMID- 23867313
TI  - Focus.

PMID- 23867314
TI  - All-trans retinoic acid potentiates the chemotherapeutic effect of cisplatin by
      inducing differentiation of tumor initiating cells in liver cancer.
AB  - BACKGROUND & AIMS: Systemic chemotherapy serves as an adjuvant treatment for post
      operation patients with hepatocellular carcinoma (HCC), and provides curative
      option for the patients with unresectable HCC. However, its efficiency is largely
      limited because of the high incidence of chemo-resistance. Increasing evidence
      has shown that tumor initiating cells (TICs) not only have the ability to self
      renew and drive the initiation and progression of cancer, but also exhibit
      greater resistance to conventional chemo- and radio-therapies than non-TICs. It
      was the aim of this study to investigate the effects of ATRA with and without
      cisplatin on TIC differentiation and apoptosis in human HCC. METHODS: In the
      present study, we evaluated the TICs of HCC cell differentiation induced by all
      trans retinoic acid (ATRA), and developed a novel chemotherapeutic approach to
      HCC, by characterizing the function of combinatorial treatment with cis
      diammineplatinum(II) (cisplatin) and ATRA in vitro and in vivo. RESULTS: ATRA
      effectively induced differentiation of TICs, which potentiated the cytotoxic
      effects of cisplatin. The combinatorial treatment of ATRA acid and cisplatin
      reduced protein kinase B (AKT) (Thr308) phosphorylation, and promoted apoptosis
      of HCC cells more significantly than treatment with cisplatin alone. In addition,
      the combined treatment with the two drugs exerted stronger inhibition on either
      HCC cell migration in vitro or metastasis in vivo, when compared to the treatment
      with either drug alone. CONCLUSIONS: These results indicated that ATRA could
      significantly improve the effect of cisplatin, which is at least partially
      attributed to ATRA-induced differentiation of HCC TICs, and the subsequent
      decrease in this chemo-resistant subpopulation.

PMID- 23867315
TI  - Systemically delivered measles virus-infected mesenchymal stem cells can evade
      host immunity to inhibit liver cancer growth.
AB  - BACKGROUND & AIMS: Although attenuated measles virus (MV) has demonstrated potent
      oncolytic activities towards human cancers, it has not yet been widely adopted
      into clinical practice. One of the major hurdles is the presence of pre-existing
      anti-MV immunity in the recipients. In this study, we have evaluated the
      combination of the potent oncolytic activity of the attenuated MV with the unique
      immunoprivileged and tumor-tropic biological properties of human bone marrow
      derived mesenchymal stem cells (BM-hMSCs) to combat human hepatocellular
      carcinoma (HCC), orthotopically implanted in SCID mice, passively immunized with
      human neutralizing antibodies against MV as a preclinical model. METHODS: SCID
      mice were orthotopically implanted with patient-derived HCC tissues and
      established HCC cell lines. SCID mice were passively immunized with human
      neutralizing anti-measles antibodies. Bioluminescence and fluorescence imaging
      were employed to monitor the ability of systemically delivered MV-infected BM
      hMSCs to infiltrate the implanted tumors and their effects on tumor growth.
      RESULTS: Systemically delivered MV-infected BM-hMSCs homed to the HCC tumors
      implanted orthotopically in the liver and it was evidenced that BM-hMSCs could
      transfer MV infectivity to HCC via heterofusion. Furthermore, therapy with MV
      infected BM-hMSCs resulted in significant inhibition of tumor growth in both
      measles antibody-naive and passively-immunized SCID mice. By contrast, when cell
      free MV viruses were delivered systemically, antitumor activity was evident only
      in measles antibody-naive SCID mice. CONCLUSIONS: MV-infected BM-hMSCs cell
      delivery system provides a feasible strategy to elude the presence of immunity
      against MV in most of the potential cancer patients to be treated with the
      oncolytic MV viruses.

PMID- 23867316
TI  - Prometheus' little helper, a novel role for fibroblast growth factor 15 in
      compensatory liver growth.

PMID- 23867317
TI  - Adiponectin and resistin protect steatotic livers undergoing transplantation.
AB  - BACKGROUND & AIMS: Numerous steatotic livers are discarded for transplantation
      because of their poor tolerance to ischemia-reperfusion. Controversial roles for
      adiponectin and related adipocytokines visfatin and resistin have been described
      in different liver pathologies, nevertheless it is unknown their possible
      implication in ischemia-reperfusion injury associated with liver transplantation.
      Our study aimed at characterizing the role of the adiponectin-derived molecular
      pathway in transplantation with steatotic and non-steatotic liver grafts.
      METHODS: Steatotic and non-steatotic liver transplantation was carried out and
      the hepatic levels of adiponectin, visfatin and resistin were measured and
      modulated either pharmacologically or surgically. RESULTS: Steatotic liver grafts
      exhibited downregulation of both adiponectin and resistin when subjected to
      transplantation. Adiponectin pre-treatment only protected steatotic grafts and
      did it so through a visfatin-independent and resistin-dependent mechanism.
      Adiponectin-derived resistin accumulation activated the PI3K/Akt pathway,
      unravelling AMPK as an upstream mediator of adiponectin's actions in steatotic
      grafts. Strategies aimed at increasing adiponectin including either AMPK
      activators or the induction of ischemic preconditioning (which activates AMPK)
      increased resistin accumulation, prevented the downregulation of PI3K/Akt pathway
      and protected steatotic liver grafts. Conversely, PI3K/Akt pathway upregulation
      and hepatic protection induced by adiponectin were abolished when resistin action
      was inhibited. CONCLUSIONS: Our findings reveal a new protective pathway in
      steatotic liver transplantation, namely AMPK-adiponectin-resistin-PI3K/Akt, which
      may help develop new strategies aimed at increasing either adiponectin or
      resistin in the steatotic liver undergoing transplant to ultimately increase
      organ donor pool and reduce waiting list.

PMID- 23867318
TI  - Reduced exposure to calcineurin inhibitors early after liver transplantation
      prevents recurrence of hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Recurrence of hepatocellular carcinoma (HCC) is a major
      complication after liver transplantation (LT). The initial immunosuppression
      protocol may influence HCC recurrence, but the optimal regimen is still unknown.
      METHODS: 219 HCC consecutive patients under Milan criteria, who received an LT at
      2 European centres between 2000 and 2010, were included. Median follow-up was 51
      months (IQR 26-93). Demographic characteristics, HCC features, and
      immunosuppression protocol within the first month after LT were evaluated against
      HCC recurrence by using Cox regression. RESULTS: In the explanted liver, 110
      patients (50%) had multinodular HCC, and largest nodule diameter was 3+/-2.1cm.
      Macrovascular invasion was incidentally detected in 11 patients (5%), and
      microvascular invasion was present in 41 patients (18.7%). HCC recurrence rates
      were 13.3% at 3 years and 17.6% at 5 years. HCC recurrence was not influenced by
      the use/non-use of steroids and antimetabolites (p=0.69 and p=0.70 respectively),
      and was similar with tacrolimus or cyclosporine (p=0.25). Higher exposure to
      calcineurin inhibitors within the first month after LT (mean tacrolimus trough
      concentrations >10ng/ml or cyclosporine trough concentrations >300ng/ml), but not
      thereafter, was associated with increased risk of HCC recurrence (27.7% vs. 14.7%
      at 5 years; p=0.007). The independent predictors of HCC recurrence by
      multivariate analysis were: high exposure to calcineurin inhibitors defined as
      above (RR=2.82; p=0.005), diameter of the largest nodule (RR=1.31; p<0.001),
      microvascular invasion (RR=2.98; p=0.003) and macrovascular invasion (RR=4.57;
      p=0.003). CONCLUSIONS: Immunosuppression protocols with early CNI minimization
      should be preferred in LT patients with HCC in order to minimize tumour
      recurrence.

PMID- 23867320
TI  - Management of anemia induced by triple therapy in patients with chronic hepatitis
      C: challenges, opportunities and recommendations.
AB  - The addition of protease inhibitors, boceprevir or telaprevir, to
      peginterferon+ribavirin (PegIFN/RBV) increases the frequency as well as the
      severity, and hence, clinical relevance of anemia, which has now become one of
      the major complications associated with triple therapy. Most significant factors
      associated with anemia in patients receiving triple therapy include older age,
      lower body mass index (BMI), advanced fibrosis, and lower baseline hemoglobin.
      The variability in inosine triphosphate pyrophosphatase (ITPA) gene, which
      encodes a protein that hydrolyses inosine triphosphate (ITP), has been identified
      as an essential genetic factor for anemia both in dual and triple therapy. The
      correct management of anemia is based on anticipation, characterization and
      therapeutic management. Basically, anemia can be characterized in 3 types:
      ferropenic (mostly in fertile women), thalassemic type hemolytic anemia, and
      anemia from chronic processes. Functional deficit of iron should also be excluded
      in patients with normal ferritin and lower saturation of transferrin. Ribavirin
      dose reduction and epoetin, sequentially, are indicated in the management of
      anemia. Epoetin non-response can be caused by lack of time, type of anemia,
      functional iron deficit or erythropoietin resistance. In the transplantation
      setting, adding a protease inhibitor to PegIFN/RBV results in a significant
      increase in the incidence and severity of anemia and, as a consequence, a greater
      need for epoetin, transfusions, and ribavirin dose reductions. Packed red cell
      transfusions are utilized when hemoglobin decreases to less than 7.5g/dl and/or
      there are clinical symptoms and/or there is no response to other therapeutic
      measures. 

PMID- 23867319
TI  - KEAP1-NRF2 complex in ischemia-induced hepatocellular damage of mouse liver
      transplants.
AB  - BACKGROUND & AIMS: The Keap1-Nrf2 signaling pathway regulates host cell defense
      responses against oxidative stress and maintains the cellular redox balance.
      METHODS: We investigated the function/molecular mechanisms by which Keap1-Nrf2
      complex may influence liver ischemia/reperfusion injury (IRI) in a mouse model of
      hepatic cold storage (20h at 4 degrees C) followed by orthotopic liver
      transplantation (OLT). RESULTS: The Keap1 hepatocyte-specific knockout (HKO) in
      the donor liver ameliorated post-transplant IRI, evidenced by improved
      hepatocellular function and OLT outcomes (Keap1 HKO->Keap1 HKO; 100% survival),
      as compared with controls (WT->WT; 50% survival; p<0.01). By contrast, donor
      liver Nrf2 deficiency exacerbated IRI in transplant recipients (Nrf2 KO->Nrf2 KO;
      40% survival). Ablation of Keap1 signaling reduced macrophage/neutrophil
      trafficking, pro-inflammatory cytokine programs, and hepatocellular
      necrosis/apoptosis, while simultaneously promoting anti-apoptotic functions in
      OLTs. At the molecular level, Keap1 HKO increased Nrf2 levels, stimulated Akt
      phosphorylation, and enhanced expression of anti-oxidant Trx1, HIF-1alpha, and HO
      1. Pretreatment of liver donors with PI3K inhibitor (LY294002) disrupted Akt/HIF
      1A signaling and recreated hepatocellular damage in otherwise IR-resistant Keap1
      HKO transplants. In parallel in vitro studies, hydrogen peroxide-stressed Keap1
      deficient hepatocytes were characterized by enhanced expression of Nrf2, Trx1,
      and Akt phosphorylation, in association with decreased release of lactate
      dehydrogenase (LDH) in cell culture supernatants. CONCLUSIONS: Keap1-Nrf2 complex
      prevents oxidative injury in IR-stressed OLTs through Keap1 signaling, which
      negatively regulates Nrf2 pathway. Activation of Nrf2 induces Trx1 and promotes
      PI3K/Akt, crucial for HIF-1alpha activity. HIF-1alpha-mediated overexpression of
      HO-1/Cyclin D1 facilitates cytoprotection by limiting hepatic inflammatory
      responses, and hepatocellular necrosis/apoptosis in a PI3K-dependent manner.

PMID- 23867322
TI  - Electrical potentials between stent-grafts made from different metals induce
      negligible corrosion.
AB  - OBJECTIVE: Evaluation of the risk of galvanic corrosion in various stent-grafts
      in current practice, when devices with unmatched alloy compositions are deployed
      together. METHOD: Five nitinol (NT) and two steel (SS) stent-grafts produced by
      different companies were used in different combinations to create 21 samples
      (NT:NT, n = 10; NT:SS, n = 10; SS:SS, n = 1). Electric potential was measured
      between the metal couplings after immersion in 0.9% NaCl at a temperature of 37 
      degrees C. Subsequently, the same samples were incubated for 24 months in 0.9%
      NaCl at 37-39  degrees C under hermetic conditions and examined under a scanning
      electron microscope in order to search for any evidence of corrosion. RESULTS:
      Electric potentials between different metals alloys were found (means: NT:SS, 181
      MUV; NT:NT, 101 MUV; SS:SS, 160 MUV). The mean electrical potential between
      stainless steel and nitinol samples was significantly higher than between NT:NT
      couplings (p < .001). During the final scanning electron microscope examination,
      only one spot of pitting corrosion (>10 MUm) on a nitinol surface was found
      (associated with previous mechanical damage) in an NT:SS sample after 24 months
      of incubation in vitro and no sign of mechanical failure of the wires was found.
      CONCLUSION: Direct contact between the stainless steel and the nitinol alloys
      does indeed create electrical potential but with a minimal risk of galvanic
      corrosion. No evidence was found for significant galvanic corrosion when two
      endovascular implants (stent-grafts) made from different metal composition were
      used in the same procedure.

PMID- 23867321
TI  - pncA gene expression and prediction factors on pyrazinamide resistance in
      Mycobacterium tuberculosis.
AB  - Mutations in the pyrazinamidase (PZAse) coding gene, pncA, have been considered
      as the main cause of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis.
      However, recent studies suggest there is no single mechanism of resistance to
      PZA. The pyrazinoic acid (POA) efflux rate is the basis of the PZA susceptibility
      Wayne test, and its quantitative measurement has been found to be a highly
      sensitive and specific predictor of PZA resistance. Based on biological
      considerations, the POA efflux rate is directly determined by the PZAse activity,
      the level of pncA expression, and the efficiency of the POA efflux pump system.
      This study analyzes the individual and the adjusted contribution of PZAse
      activity, pncA expression and POA efflux rate on PZA resistance. Thirty M.
      tuberculosis strains with known microbiological PZA susceptibility or resistance
      were analyzed. For each strain, PZAse was recombinantly produced and its
      enzymatic activity measured. The level of pncA mRNA was estimated by quantitative
      RT-PCR, and the POA efflux rate was determined. Mutations in the pncA promoter
      were detected by DNA sequencing. All factors were evaluated by multiple
      regression analysis to determine their adjusted effects on the level of PZA
      resistance. Low level of pncA expression associated to mutations in the pncA
      promoter region was observed in pncA wild type resistant strains. POA efflux rate
      was the best predictor after adjusting for the other factors, followed by PZAse
      activity. These results suggest that tests which rely on pncA mutations or PZAse
      activity are likely to be less predictive of real PZA resistance than tests which
      measure the rate of POA efflux. This should be further analyzed in light of the
      development of alternate assays to determine PZA resistance. 

PMID- 23867323
TI  - Continuous production of iron-based nanocrystals by laser pyrolysis. Effect of
      operating variables on size, composition and magnetic response.
AB  - Well dispersed iron-based magnetic nanoparticles have been prepared by gas phase
      laser-driven decomposition of iron pentacarbonyl. Agglomeration of the newly
      synthesized nanoparticles could be avoided by using a liquid collection system in
      which the exit stream from the laser reactor was bubbled through triethylene
      glycol (TREG). The effect of different experimental parameters (precursor
      concentration, laser power, working pressure, residence time) was studied and, by
      selecting the appropriate conditions, the size of the resulting magnetic
      nanocrystals could be tuned from ultrasmall (ca. 2.5 nm) to around 12 nm. For
      nanoparticle sizes around 10 nm and larger a metallic iron core could be
      preserved. These iron/iron oxide core-shell compositions exhibit very high values
      of magnetization, 127 emu g(-1). 

PMID- 23867325
TI  - 2011 Consensus of the French Endocrine Society: "hypoglycaemia in non-diabetic
      adult patients".

PMID- 23867326
TI  - Combination of multiplex PCR with denaturing high-performance liquid
      chromatography for rapid detection of Mycobacterium genus and simultaneous
      identification of the Mycobacterium tuberculosis complex.
AB  - A new assay with the combination of multiplex polymerase chain reaction and
      denaturing high-performance liquid chromatography analysis was developed for
      simultaneous detection of Mycobacterium genus and identification of the
      Mycobacterium tuberculosis complex (MTC). Targeting at genus-specific 16S rRNA
      sequence of Mycobacterium and specific insertion elements IS6110 and IS1081 of
      MTC, the assay was validated with 84 strains covering 23 mycobacteria species and
      30 strains of non-mycobacteria species. No cross reactivity was observed.
      Clinical application was carried out on 198 specimens (155 human sputum and 43
      bovine tissue samples) and compared with culture. The multiplex assay detected
      all culture-positive (36 in number) and 35.2% (57/162) culture-negative
      specimens. The molecular assay was fast that could be completed within 1 h on
      purified DNA, with the limit of detection as 0.8-1.6 pg per reaction on DNA
      template. This work provided a useful laboratory tool for rapid identification of
      Mycobacterium and differentiation of MTC and nontuberculous mycobacteria. 

PMID- 23867327
TI  - The performance of 4 different supplements and 5 blood culture bottles types in
      detection of bacteria and Candida spp. in simulated sterile body fluid cultures.
AB  - The purpose of this investigation was to evaluate the performance of 4
      supplements: horse blood, fastidious organisms supplement (FOS), haemin
      isovitalex albumine (HIA), and brain heart infusion-haemin isovitalex albumine
      (BHI-HIA) and 5 blood culture bottles: Bactec Mycosis IC/F, Plus Aerobic/F, Peds
      Plus/F from the Bactec 9240 system, and BacT/Alert FA and BacT/Alert PF from the
      BacT/Alert 3D system, in detection of bacteria and Candida spp. in simulated
      sterile body fluids other than blood models. In total, 8 reference strains
      (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae,
      Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Candida
      albicans, and Candida parapsilosis) and 11 clinical bacteria and yeast isolates
      (6 isolates from cerebrospinal fluid and 5 isolates from blood) were included in
      this study. Horse blood, FOS, and HIA were significantly better than no
      supplements (P < 0.0001, P < 0.0002, and P = 0.05, respectively) in detection of
      bacteria. Interestingly, there was no significant difference between BHI-HIA and
      bottles without any supplements. Sixty bottles analyzed of which 59 (98.33%)
      bottles with horse blood, 53 (88.33%) with FOS, 45 (75.00%) with HIA, and 43
      (71.67%) with BHI-HIA signaled positive. The positivity rates with horse blood
      were significantly higher than with HIA and BHI-HIA (P < 0.0005 and P < 0.0001,
      respectively). Similarly, the blood culture bottles with horse blood had shorter
      time to detection (TTD) compared to bottles with FOS and HIA (P < 0.05 and P <
      0.0001, respectively). When yeasts were analyzed, almost all (124/125) blood
      culture bottles with Candida spp. signaled positive even in the absence of
      supplements. Bactec Mycosis IC/F had significantly shorter TTD compared to Bactec
      Peds Plus/F, Bactec Plus Aerobic/F, BacT/Alert FA, and BacT/Alert PF bottles in
      detection of Candida spp. (P < 0.005, P < 0.05, P < 0.001, and P < 0.001,
      respectively). The present study showed that horse blood was the most effective
      supplement in growth of bacteria in the blood culture bottles that were analyzed
      in the study. 

PMID- 23867328
TI  - Performance of stool cultures before and after a 3-day hospitalization: fewer
      cultures, better for patients and for money.
AB  - We evaluated retrospectively the yield of stool culture (SC) depending on the
      length of hospitalization, and we characterized the patients missed by the 3-day
      rejection rule. SC detects bacterial enteric pathogens (Campylobacter spp.,
      Salmonella enterica, Yersinia spp., Shigella spp.). During this 5-year study
      period, 13,039 SCs were requested, and 376 were positive (2.9%). The yield of SC
      dropped from 11.7% before 3 days of hospitalization to 0.7% after 3 days in
      children and 4.3% to 0.3% in adults. Finally, only 13 clinically relevant cases
      (0.2% of SC prescribed after 3 days) were undiagnosed by strict application of
      the 3-day rule. In conclusion, rejection of SC prescribed after 3 days of
      hospitalization allows to reduce workload by 37.8% for children and 65.7% for
      adults, representing a cost of ?12,500 ($16,250) per year in our hospital. 

PMID- 23867329
TI  - Characteristics of IFN-gamma responses in IGRA among pulmonary TB suspects in a
      TB-endemic area.
AB  - Although the diagnostic value of interferon-gamma (IFN-gamma) release assays for
      active tuberculosis (TB) is limited, the characteristic of non-TB-specific IFN
      gamma responses among TB suspects deserves further evaluation. We enrolled
      clinically suspected pulmonary TB (PTB) patients, and QuantiFERON-TB Gold In-Tube
      (QFT-GIT) was performed. The characteristics of IFN-gamma responses were
      analyzed. Among 392 patients, active PTB patients had stronger IFN-gamma
      responses to TB antigen (TBAg-Nil, P < 0.001) and lower responses to mitogen
      (Mitogen-Nil, P < 0.001). Lower body mass index (P = 0.001), without bacille
      Calmette-Guerin vaccination (P = 0.026), and active PTB (P = 0.011) were
      independent factors associated with lower non-TB-specific IFN-gamma responses.
      Among TB suspects with higher TBAg-Nil (>1.02 U/mL) and lower Mitogen-Nil (<5.5
      U/mL), 84.3% were active PTB cases. Among TB suspects with lower TBAg-Nil and
      higher Mitogen-Nil, only 4.7% were active PTB. The present study suggested that
      the possibilities of active PTB should be carefully excluded in TB suspects with
      stronger TB-specific and lower non-TB-specific IFN-gamma responses in QFT-GIT. 

PMID- 23867330
TI  - Prognostic value of global left ventricular strain for conservatively treated
      patients with symptomatic aortic stenosis.
AB  - AIMS: Impaired left ventricular (LV) strain is associated with an increased risk
      of cardiac events in asymptomatic severe aortic stenosis (AS). We aimed to
      evaluate the prognostic value of global LV strain in conservatively treated
      patients with symptomatic AS. METHODS AND RESULTS: This cohort study
      retrospectively reviewed symptomatic AS patients who were treated conservatively
      or surgically between July 2007 and April 2010. We measured their global
      longitudinal strain (GLS) and global circumferential strain (GCS). Clinical
      events were defined as readmission for heart failure or all-cause death for 2
      years. GLS and GCS could predict a worse outcome in the conservatively treated
      group at cut-offs of =-16.5% (77% sensitivity and 67% specificity) and =-22.2%
      (92% sensitivity and 83% specificity), respectively. By univariate Cox regression
      analysis, age, logistic EuroSCORE, aortic valve area, GLS, and GCS were
      significant predictors. When adjusted for age, logistic EuroSCORE, and aortic
      valve area, impaired GLS and GCS were independently associated with a higher risk
      of clinical events. CONCLUSION: In conservatively treated patients with
      symptomatic AS, impaired GLS and GCS were associated with an increased risk of
      cardiac events during a 2-year follow-up. Global LV strain may help to define a
      higher risk subset; therefore, a larger and prospective observation study would
      be necessary.

PMID- 23867331
TI  - High-sensitivity cardiac troponin T for earlier diagnosis of acute myocardial
      infarction in patients with initially negative troponin T test--comparison
      between cardiac markers.
AB  - BACKGROUND AND PURPOSE: An early diagnosis is essential for therapeutic decision
      and risk stratification in patients with suspected acute myocardial infarction
      (AMI). We analyzed and compared the diagnostic value of high-sensitivity troponin
      T (hs-TnT) and other cardiac markers in patients with an initially negative
      troponin T test at presentation. METHODS AND SUBJECTS: The present study was a
      prospective, multicenter study including five participating emergency
      cardiovascular tertiary centers in Japan. From November 2009 through January
      2011, patients with suspected AMI at the emergency room with an initial troponin
      T (c-TnT) test <100 ng/L were enrolled. RESULTS: A total of 85 patients were
      prospectively assigned from five participating emergency cardiovascular tertiary
      centers in Japan. The median time from the onset of chest pain to the T0 sampling
      was 165 min [IQR 120-180]. The final diagnoses according to the recent universal
      definition and other standard cut-off values were AMI in 47, unstable angina in
      12, and non AMI in 38 patients. The overall ROC-AUC value of hs-TnT, c-TnT,
      creatine kinase MB, and heart-type fatty acid-binding protein were 0.810, 0.716,
      0.782, and 0.880, respectively. The diagnostic sensitivity and negative
      predictive value of hs-TnT were both 100% for the patients admitted more than 120
      min from the onset, however the specificity was limited for the whole time
      windows (71%). The absolute value change of the hs-TnT from T0 to T3 sampling 3h
      later improved the ROC-AUC up to 0.972 and the specificity was 92% at 22 ng/L
      (ROC-optimized cut-off) and 100% at 105 ng/L (rule-in cut-off). CONCLUSIONS: The
      hs-TnT displayed 100% sensitivity and negative predictive value for the patients
      admitted more than 120 min from the onset, however the specificity was limited.
      The absolute change from T0 to T3 (22 ng/L) improved the total diagnostic
      performance.

PMID- 23867332
TI  - Serum 25-hydroxyvitamin D is associated with both arterial and ventricular
      stiffness in healthy subjects.
AB  - BACKGROUND: Vitamin D regulates the renin-angiotensin system, suppresses
      proliferation of vascular smooth muscle and improves endothelial cell dependent
      vasodilatation. These mechanisms may play a role on pathogenesis of arterial and
      left ventricular stiffness. OBJECTIVES: We aimed to investigate the association
      between serum 25-hydroxyvitamin D with arterial and left ventricular stiffness in
      healthy subjects. METHODS: We studied 125 healthy subjects without known
      cardiovascular risk factors or overt heart disease (mean age: 60.2 +/- 11.9
      years). Serum 25-hydroxyvitamin D was measured using a direct competitive
      chemiluminescent immunoassay. The subjects were divided into two groups according
      to the serum vitamin D level; vitamin D sufficient (>= 20 ng/ml, n = 56) and
      vitamin D deficient (<20 ng/ml, n = 69). Indexes of LV stiffness such as E/A and
      E/E' were measured. Pulse wave velocity (PWV), which reflects arterial stiffness,
      was calculated using the single-point method via the Mobil-O-Graph((r)) ARC
      solver algorithm. RESULTS: Systolic blood pressure, level of serum calcium, PWV
      and E/E' values were higher and E/A values were lower in vitamin D deficient
      group compared with vitamin D sufficient group. Multiple linear regression
      analysis showed that vitamin D level was independently associated with E/E' (beta
      = -0.364, p<0.001), serum calcium (r = -0.136, p = 0.014), PWV (beta = -0.203, p
      = 0.003), E/A (beta = 0.209, p = 0.001) and systolic blood pressure (beta = 
      0.293, p<0.001). CONCLUSION: 25-Hydroxyvitamin D levels are associated with
      increased ventricular and arterial stiffness as well as systolic blood pressure
      in healthy subjects.

PMID- 23867333
TI  - Comparison of adhesion forces developed by foil mesh of various dimensions
      applied in combination with composites of different viscosity.
AB  - OBJECTIVES: The aim of this study was to determine what effect various
      combinations of particular bracket bases and composites of different viscosity
      have on adhesion force. MATERIALS AND METHODS: Eighty extracted premolars, upper
      and lower, were randomly assigned to four groups of 20 teeth and the combinations
      of either flowable or paste composite and brackets with either 80-gauge or 100
      gauge foil mesh were applied to their labial surfaces accordingly: group A:
      flowable composite+80-mesh base; group B: flowable composite+100-mesh base; group
      C: paste composite+80-gauge base; group D: paste composite+100-gauge base. Each
      sample was subjected to shear bond stress to failure using a Zwick Roell Z050
      testing machine at 50N/min load. The load required to detach each bracket was
      recorded in N and subsequently converted to MPa. After debonding, each tooth was
      analysed under optical microscope at 12* magnification and photographed prior to
      calculation of the Adhesive Remnant Index (ARI). RESULTS: The paste composite
      showed greater adhesion strength than the flowable in all cases, but this was
      further increased when the 80-gauge, rather than the 100-gauge, mesh was used. No
      statistically significant difference in ARI values was found between the flowable
      groups (groups A and B), on the other hand, in the paste composite groups, a
      statistically significant difference was highlighted between the 80-gauge (group
      D) and 100-gauge (group C) mesh bracket bases. CONCLUSIONS: Both the density of
      the composite and the gauge of a mesh bracket base are able to influence bond
      strength and the bond failure interface.

PMID- 23867336
TI  - Factors associated with the efficacy of mandibular advancing device treatment in
      adult OSA patients.
AB  - The aim of this study was to evaluate the anthropometric, demographic, occlusal
      and cephalometric characteristics of a group of adult obstructive sleep apnea
      (OSA) patients treated with mandibular advancement devices (MADs) and to
      determine the factors associated with treatment efficacy. Twenty-three
      consecutive patients with mild to severe OSA (polysomnographically diagnosed
      [T0]) were recruited for this prospective study; they were treated with a
      Silensor((r)) appliance, and a polysomnographic exam with the MAD in situ was
      performed 2 to 3 months later (T1) to evaluate MAD's efficacy. Based on apnea
      hypopnea index (AHI) differences between the T0 and T1 values, patients were
      classified into two groups: completely recovered and not completely recovered
      patients. The differences in anthropometric, demographic, occlusal and
      cephalometric parameters between the two groups were analyzed, and significant
      parameters verified. The sample showed these prevalent characteristics: deep
      bite, crossbite, tooth wear, dental and skeletal Class II, mesofacial mandibular
      vertical growth pattern, low position of the hyoid bone, longer soft palate
      length. The transverse diameters of upper maxilla had the greatest impact on T0
      AHI. The factors associated with MAD efficacy were: age under 55 years, distance
      between the hyoid bone and the mandibular plane (H-MP) less than 20 mm,
      divergence of mandibular vertical growth pattern (SN^MP) less than 29 degrees .

PMID- 23867337
TI  - High-resolution multiphoton cryomicroscopy.
AB  - An ultracompact high-resolution multiphoton cryomicroscope with a femtosecond
      near infrared fiber laser has been utilized to study the cellular
      autofluorescence during freezing and thawing of cells. Cooling resulted in an
      increase of the intracellular fluorescence intensity followed by morphological
      modifications at temperatures below -10  degrees C, depending on the application
      of the cryoprotectant DMSO and the cooling rate. Furthermore, fluorescence
      lifetime imaging revealed an increase of the mean lifetime with a decrease in
      temperature. Non-destructive, label-free optical biopsies of biomaterial in ice
      can be obtained with sub-20 mW mean powers.

PMID- 23867338
TI  - Genetic manipulation of B cells for the isolation of rare therapeutic antibodies
      from the human repertoire.
AB  - Antibody based therapies are increasingly applied to prevent and treat human
      disease. While the majority of antibodies currently on the market are chimeric or
      humanized antibodies from rodents, the focus has now shifted to the isolation and
      development of fully human antibodies. By retroviral transduction of B cell
      lymphoma-6 (BCL-6), which prevents terminal differentiation of B cells and, the
      anti-apoptotic gene B-cell lymphoma-extra large (Bcl-xL) into primary human B
      cells we efficiently immortalize antibody-producing B cells allowing the
      isolation of therapeutic antibodies. Selection of antigen-specific B cell clones
      was greatly facilitated because the transduced B cells retain surface
      immunoglobulin expression and secrete immunoglobulin into the culture
      supernatant. Surface immunoglobulin expression can be utilized to stain and
      isolate antigen specific B cell clones with labeled antigen. Immunoglobulins
      secreted in culture supernatant can directly be tested in functional assays to
      identify unique B cell clones. Here we describe the key features of our Bcl-6/Bcl
      xL culture platform (AIMSelect). 

PMID- 23867340
TI  - Improved genome-wide mapping of uncapped and cleaved transcripts in eukaryotes-
      GMUCT 2.0.
AB  - The advent of high-throughput sequencing has led to an explosion of studies into
      the diversity, expression, processing, and lifespan of RNAs. Recently, three
      different high-throughput sequencing-based methods have been developed to
      specifically study RNAs that are in the process of being degraded. All three
      methods-genome-wide mapping of uncapped and cleaved transcripts (GMUCT), parallel
      analysis of RNA ends (PARE), and degradome sequencing-take advantage of the fact
      that Illumina sequencing libraries use T4 RNA ligase 1 to ligate an adapter to
      the 5' end of RNAs that have a free 5'-monophosphate. This condition for T4 RNA
      ligase 1 substrates means that mature mRNAs are not substrates of the enzyme
      because they have a 5'-cap moiety. As a result, these sequencing libraries are
      specifically made up of clones of decapped or degrading mRNAs resulting from 5'
      to-3' or nonsense-mediated decay (NMD) and the 3' fragment of cleaved microRNA
      (miRNA) and small interfering RNA (siRNA) target RNAs. Here, we present a
      massively streamlined protocol for GMUCT that takes 2-3days, can be initiated
      with as little as 5MUg of starting total RNA, and involves only one gel size
      selection step. We show that the resulting datasets are similar to those produced
      using the previous GMUCT and PARE protocols. In total, our results suggest that
      this method will be the preferable approach for future studies of RNA degradation
      intermediates and small RNA-mediated cleavage in eukaryotic transcriptomes. 

PMID- 23867339
TI  - Humanized FcRn mouse models for evaluating pharmacokinetics of human IgG
      antibodies.
AB  - A key element for the successful development of novel therapeutic antibodies is
      to fully understand their pharmacokinetic and pharmacodynamic behavior before
      performing clinical trials. While many in vitro modeling approaches exist, these
      simply cannot substitute for data obtained from appropriate animal models. It was
      established quite early that the unusual long serum half-life of immunoglobulin
      G's (IgGs) and Fc domains are due to their rescue and recycling by the neonatal
      Fc receptor (FcRn). The diverse roles of FcRn became apparent after isolation and
      cloning. Interesting are the significant species differences between rodent and
      human FcRn reactivity, rendering wild type rodents an inadequate model for
      studying IgG serum half-life. With the advance of genetic engineering mouse
      models have been established expressing human FcRn, and lacking mouse FcRn
      protein. These models have become highly relevant tools for serum half-life
      analysis of Fc-containing compounds. 

PMID- 23867341
TI  - Label-free fluorescent DNA biosensors based on metallointercalators and
      nanomaterials.
AB  - DNA based biosensors have become increasingly important in medical diagnostics,
      genetic and drug screening, and forensics in this post-genomic era. Chemical
      labeling methods suffer from several drawbacks, which are tedious, cost-expensive
      and time-consuming, thus the development of simple and general label free
      strategies is being demanded. The present article introduces a new model of
      biosensor device based on both metallointercalators and nanomaterials, with the
      aim of highlighting, in particular, the use of the "label-free" strategy for the
      construction of simple and inexpensive sensing platforms. In this work, two
      strategies were developed for designing "label-free" sensors: (1)
      metallointercalators act as the quencher to nanomaterials; (2) nanomaterials act
      as the quencher to metallointercalators. These methods take advantage of the
      sensitive luminescence signal change of metallointercalators or nanomaterials
      upon analytes binding. By monitoring the luminescence change, we were able to
      detect metal ions and biomolecules. Compared to other label-free fluorescent
      methods, these "label-free" DNA biosensors provide fast, simple, economical,
      sensitive and selective detection of target analytes with specific probes. 

PMID- 23867342
TI  - Is the Bone-Conduction HeadBand test useful for predicting the functional outcome
      of a round window active middle ear implant?
AB  - OBJECTIVE: To estimate the reliability of the Bone Conduction-HeadBand (BC-HB)
      test for predicting the postoperative functional outcome of a round-window (RW)
      vibroplasty. STUDY DESIGN: Within-subject comparison of the functional results of
      the BC-HB test, which is routinely used for the preoperative evaluation of a bone
      conduction transducer, with an active middle ear implant (AMEI) placed onto the
      round window. SETTING: Tertiary referral university hospital center. PATIENTS:
      Seven patients with similar anatomic (absent stapes superstructure) and
      functional (moderate, mixed hearing loss) sequelae from open tympanoplasty
      technique. INTERVENTION: All subjects underwent preoperative audiologic
      assessment with the BC-HB. Subsequently, all subjects underwent surgical
      placement of an AMEI onto the round window. MAIN OUTCOME MEASURE: Pure tone and
      speech audiometry in quiet and noise were assessed. Additionally, evaluation of
      specific satisfactory targets was performed using the Client Oriented Scale of
      Improvement. RESULTS: Pure tone and speech audiometry in quiet established that
      both devices had very similar performance and provided remarkable improvement
      compared with the unaided condition. However, high-frequency gain and speech
      audiometry in noise demonstrated better performance with RW-AMEI. CONCLUSION: In
      patients presenting with mixed hearing loss as a sequela from middle ear surgery,
      the preoperative BC-HB test may be helpful in predicting the final functional
      outcome and patient satisfaction with RW-AMEI.

PMID- 23867343
TI  - Association analysis of CFH and ARMS2 gene polymorphisms in a Brazilian cohort
      with age-related macular degeneration.
AB  - PURPOSE: To investigate the association between the CFH and ARMS2 gene
      polymorphisms and age-related macular degeneration (AMD) in a Brazilian cohort.
      METHODS: We examined 163 individuals with AMD and 154 controls recruited at the
      Department of Ophthalmology of the Universidade Federal de Minas Gerais, at the
      Instituto da Visao, and at the Centro Especializado em Olhos, in Brazil, between
      2007 and 2012. Genotyping for CFH rs1061170 and ARMS2 rs10490924 single
      nucleotide polymorphisms was performed. The odds ratios (OR) for all of the
      studied genotypes (heterozygous and homozygous) of both genes were calculated
      compared to homozygous ancestral alleles. RESULTS: Homozygosity for the CFH and
      ARMS2 at-risk allele was 33.3 and 23.6%, respectively, for AMD individuals and
      10.3 and 7.1%, respectively, for controls (p < 0.0001). The OR was 7.2 (95% CI
      3.6-14.5; p < 0.001) for the CFH at-risk genotype (CC) and 5.5 (95% CI 2.6-11.8;
      p < 0.0001) for ARMS2 (TT). Subjects homozygous for both polymorphisms had a much
      higher risk of developing AMD (n = 14 patients, OR 33.3, 95% CI 12.8-86.4). The
      proportion of ancestry in each group indicated that AMD patients had a higher
      European (Caucasian) component than controls. CONCLUSION: CFH and ARMS2
      polymorphisms were strongly associated with AMD in this Brazilian cohort.

PMID- 23867344
TI  - Refractory bleeding from intestinal angiodysplasias successfully treated with
      danazol in three patients with von Willebrand disease.
AB  - von Willebrand disease (VWD) is associated with development of gastrointestinal
      (GI) vascular malformations that lead to chronic GI bleeding. Conventional
      management, including von Willebrand factor concentrate replacement and
      endoscopic ablation or bowel resection, does not consistently reduce hemorrhage.
      We describe three patients with VWD for whom conventional management failed to
      control GI bleeding. We retrospectively reviewed medical records of patients with
      VWD and GI bleeding. After patients began treatment with danazol, we observed
      long-term reductions in GI bleeding and packed red blood cell transfusion
      requirements. One patient had severe liver toxicity and was found to have
      concomitant primary biliary cirrhosis. Danazol use may be considered in patients
      with VWD and GI bleeding due to angiodysplasia that otherwise fails to respond to
      conventional treatment; the primary aim of treatment is to reduce transfusion
      dependence. The benefits are variable and possibly transient. Monitoring for
      toxicity is important when this treatment is pursued. 

PMID- 23867345
TI  - Acute disseminated intravascular coagulation developed after dilation and
      curettage in an adenomyosis patient: a case report.
AB  - We reported a rare case of acute disseminated intravascular coagulation (DIC)
      after dilation and curettage in an adenomyosis and missed abortion patient. The
      clinical performance improved after treatment with tranexamic acid, blood
      transfusions and subtotal hysterectomy. Hemorrhage, degeneration and necrosis
      were found in the myometrium. Pregnancy-related thrombotic tendency, accelerated
      uterus tissue injury after curettage, activation of coagulation system,
      microthrombosis formation, myometrium necrosis, exhaustion of coagulation factors
      and hyperfibrinolysis might play the crucial roles in the pathophysiology of
      acute DIC. Physicians should be alert that adenomyosis patients undergoing
      dilation and curettage may be in danger of DIC. 

PMID- 23867346
TI  - Myelodysplastic syndrome and associated coagulopathy: a case report and review.
AB  - Myelodysplastic syndrome (MDS) is a primary bone marrow disorder whose hallmark
      is the development of peripheral cytopenias and a predilection toward the
      development of acute myeloid leukemia (AML). Patients often have hypercellular
      bone marrows with dysplastic features that may involve multiple lineages. An
      increased awareness of MDS has led to the reporting of a number of associated
      autoimmune and paraneoplastic conditions in the medical literature. We present
      the case of an elderly man who was transferred to our institution with
      persistent, refractory bleeding several weeks after the resection of a sebaceous
      cyst. Despite reoperation, treatment with topical and intravenous hemostatic
      agents, and transfusion of blood products, the patient's bleeding persisted. A
      comprehensive evaluation for the cause of his coagulopathy was undertaken. Bone
      marrow evaluation was consistent with MDS. A paraneoplastic consumptive
      coagulopathy or fibrinolytic process in conjunction with MDS-related platelet
      dysfunction was felt to be the most likely etiology of the patient's bleeding. 

PMID- 23867347
TI  - Arsenic trioxide inhibits the Hedgehog pathway which is aberrantly activated in
      acute promyelocytic leukemia.
AB  - BACKGROUND/AIM: Dysregulated Hedgehog (Hh) signaling has been implicated in
      several human malignancies. Hh signaling inhibitors are predicted to have a
      minimal effect when the Smoothened receptor is mutated. Implications that Gli
      proteins are molecular targets of arsenic trioxide (ATO) action prompted us to
      investigate the expression of Hh signaling in acute promyelocytic leukemia (APL)
      and the influence of ATO on the Hh signaling pathway in APL. METHODS:
      Quantitative real-time reverse transcription polymerase chain reaction and
      Western blot were employed to analyze the expression of Hh pathway components and
      the influence of ATO on the Hh signaling pathway in APL. RESULTS: The expression
      of Hh pathway components was significantly upregulated in APL. In newly diagnosed
      APL patients, Gli2 expression was significantly positively correlated with Gli1
      (R = 0.57, p < 0.001) and Smo (R = 0.56, p < 0.001) and the expression of Hh
      pathway components was significantly higher in the high WBC group (p < 0.05). ATO
      can significantly downregulate the expression of Hh pathway components in vitro
      and in vivo (p < 0.05). CONCLUSION: The Hh pathway is aberrantly activated in APL
      and associated with a bad prognostic factor. ATO can effectively inhibit the
      expression of the Hh pathway. The obtained data give the first clinical evidence
      for the application of ATO in tumors exhibiting an aberrantly activated Hh
      pathway.

PMID- 23867348
TI  - An anatomic study of local infiltration analgesia in total knee arthroplasty.
AB  - BACKGROUND: Local infiltration analgesia (LIA) is a relatively novel technique
      developed for effective pain control following total knee arthroplasty (TKA),
      reducing requirements for epidural or parenteral postoperative analgesia. This
      study investigated the anatomical spread of an LIA used in TKA to identify the
      nerve structures reached by the injected fluid. METHODS: Six fresh-frozen
      cadaveric lower limbs were injected according to a standardised LIA technique
      with a solution of latex and India ink to enable visualisation. Wounds were
      closed and limbs placed flat in a freezer at -20 degrees C for two weeks. Limbs
      were then either sliced or dissected to identify solution locations. RESULTS:
      Solution was found from the proximal thigh to the middle of the lower leg. The
      main areas of concentration were the popliteal fossa, the anterior aspect of the
      femur and the subcutaneous tissue of the anterior aspect of the knee. There was
      less solution in the lower popliteal fossa. The solution was found to reach the
      majority of nerves, with good infiltration of nerves supplying the knee.
      CONCLUSIONS: These results support the positive clinical outcomes with this LIA
      technique. However, the lack of infiltration into the lower popliteal fossa
      suggests more fluid or a different injection point could be used. The solution
      reaching the extensor muscles of the lower leg is likely to have no beneficial
      analgesic effect for a TKA patient. The LIA technique is already used in clinical
      practice following total knee arthroplasty. Results from this study show there
      may be scope to optimise the injection sites in LIA technique.

PMID- 23867349
TI  - OPN -443C>T genetic polymorphism and tumor OPN expression are associated with the
      risk and clinical features of papillary thyroid cancer in a Chinese cohort.
AB  - AIM: to test the possible association between the polymorphism of Osteopontin
      (OPN) gene with the risk and the clinical features of papillary thyroid cancer
      (PTC). METHODS: A total of 363 PTC patients and 413 healthy controls were
      enrolled. OPN expressions in tumor tissue were detected by immunohistochemistry.
      OPN gene polymorphisms, namely, -66T>G (rs28357094), -156G>GG (rs17524488), and 
      443C>T (rs11730582), were determined. RESULTS: We observed that the PTC patients
      had significantly higher rates of -443TT genotypes than controls (P<0.001). The
      multivariate logistic regression analysis showed a significantly increased risk
      for PTC for the -443CC genotype compared with the -443TT genotype (adjusted OR=
      4.312, 95%CI: 2.747 -6.987, adjusted P < 0.001). OPN protein was not expressed in
      normal thyroid tissues while tumor samples from PTC patients were shown to have
      high expressions of OPN. Also, we found that the high OPN expressions were
      significantly more prevalent in -443CC carriers than TT carriers (P <0.001). Both
      the CC carriers and OPN expression were closely associated with the cervical
      lymph node metastasis and angiolymphatic invasion of PTC. CONCLUSION: This study
      provides evidence to support the connection between the OPN genetic polymorphism
      and tissue expression with risk as well as the invasiveness of PTC.

PMID- 23867350
TI  - Quantifier processing can be dissociated from numerical processing: evidence from
      semantic dementia patients.
AB  - Quantifiers such as frequency adverbs (e.g., "always", "never") and quantity
      pronouns (e.g., "many", "none") convey quantity information. Whether quantifiers
      are processed as numbers or as general semantics has been a matter of much
      debate. Some neuropsychological and fMRI studies have found that the processing
      of quantifiers depends on the numerical magnitude comprehension system, but
      others have found that quantifier processing is associated with semantic
      representation. The selective impairment of language in semantic dementia
      patients provides a way to examine the above controversy. We administered a
      series of neuropsychological tests (i.e., language processing, numerical
      processing and semantic distance judgment) to two patients with different levels
      of severity in semantic dementia (mild vs. severe). The results showed that the
      two patients had intact numerical knowledge, but impairments in semantic
      processing. Moreover, the patient with severe/late semantic dementia showed more
      impairment in quantifier and semantic processing than the patient with mild/early
      semantic dementia. We concluded that quantifier processing is associated with
      general semantic processing, not with numerical processing. 

PMID- 23867351
TI  - rhEPO/EPO discrimination with ultrasensitive electrochemical biosensor based on
      sandwich-type nano-Au/ZnO sol-gel/nano-Au signal amplification.
AB  - This research established a non-labeled electrochemical biosensor for
      discrimination of recombinant human erythropoietin (rhEPO) and endogenous
      erythropoietin (EPO). We prepared a glassy carbon electrode (GCE) modified by a
      unique sandwich-like nano-Au/ZnO sol-gel/nano-Au compound membrane for signal
      amplification. The porous sol-gel structure facilitates protein activity
      maintenance and thermostability. Nano-Au is characterized by a large specific
      surface area, high surface activity, high absorbability, and good electro
      conductivity and biocompatibility. By combining the advantages of both ZnO sol
      gel and nano-Au, the amount of erythropoietin receptor (EPOR) increased
      substantially, and electron transfer of EPOR protein and electrode surface
      increased accordingly. In the present study, the effects of experimental
      conditions such as nano-Au electrodeposition time and nano-Au concentration were
      investigated by cyclic voltammetry, and the process of GCE modification was
      characterized electrochemically. We successfully developed a new method for
      electrochemical detection of trace rhEPO/EPO. More importantly, the response
      current change (DeltaI) of the nano-Au/ZnO sol-gel/nano-Au modified GCE increases
      3-fold when compared with that of the unmodified electrode and the sensor
      detection sensitivity increases significantly. In conclusion, this
      electrochemical biosensor is simple to prepare and allows fast, accurate, and
      specific detection of trace rhEPO in clinical monitoring and stimulant
      discrimination. 

PMID- 23867352
TI  - Amplified voltammetric characterization of cleavage of the biotinylated peptide
      by BACE1 and screening of BACE1 inhibitors.
AB  - Cleavage of amyloid precursor protein (APP) by the beta-site APP cleaving enzyme
      1 (BACE1) is a key step in the formation of amyloid beta (Abeta) peptide, the
      main component of amyloid plaques in Alzheimer's disease (AD). Suppression of
      BACE1 activity has thus become an efficient way for the treatment of AD. In this
      study, BACE1 in the absence or presence of BACE1 inhibitors was exposed to the
      biotinylated peptide substrate-modified electrode. This step was followed by the
      attachment of ferrocene (Fc)-capped gold nanoparticle/streptavidin conjugates.
      Due to the blockage of the BACE1 activity by select inhibitors, well-defined
      voltammetric peaks of high signal intensity were obtained. However, featureless
      voltammogram was obtained upon initiating the cleavage reaction. The proposed
      method is simple, sensitive, and suitable for monitoring of BACE1 activity and
      screening of BACE1 inhibitors. 

PMID- 23867353
TI  - Glucose microfluidic biosensors based on reversible enzyme immobilization on
      photopatterned stimuli-responsive polymer.
AB  - In this paper, we demonstrate a new strategy for replaceable enzymatic
      microreactor based on a switchable wettability interface of poly(N
      isopropylacrylamide) (PNIPAAm). PNIPAAm porous polymer monolith (PPM) with 3D
      macroporous framework is photopolymerized in glass microchip within 30 s. The
      PNIPAAm PPM not only shows its reversible swelling/shrinking property at the
      different temperature around the lower critical solution temperature (LCST), but
      also shows reversible hydrophilicity/hydrophobicity corresponding to its
      swelling/shrinking status. Based on these properties, a biocompatible and
      replaceable on-chip enzymatic microreactor has been successfully built by means
      of the reversible adsorption and release of glucose oxidase (GOx) on the robust
      and stable matrix. Coupled with a carbon fiber microelectrode as electrochemical
      detector, the microreactor has been successfully employed for detection of
      glucose with a linear range from 0.05 to 5 mM. This approach may provide a
      promising way for high efficient and renewable microreactors that will find wide
      application in clinical diagnosis, biochemical synthesis/analysis, and proteomic
      research.

PMID- 23867354
TI  - Relative source allocation of TDI to drinking water for derivation of a criterion
      for chloroform: a Monte-Carlo and multi-exposure assessment.
AB  - Drinking water quality standard (DWQS) criteria for chemicals for which there is
      a threshold for toxicity are derived by allocating a fraction of tolerable daily
      intake (TDI) to exposure from drinking water. We conducted physiologically based
      pharmacokinetic model simulations for chloroform and have proposed an equation
      for total oral-equivalent potential intake via three routes (oral ingestion,
      inhalation, and dermal exposures), the biologically effective doses of which were
      converted to oral-equivalent potential intakes. The probability distributions of
      total oral-equivalent potential intake in Japanese people were estimated by Monte
      Carlo simulations. Even when the chloroform concentration in drinking water
      equaled the current DWQS criterion, there was sufficient margin between the
      intake and the TDI: the probability that the intake exceeded TDI was below 0.1%.
      If a criterion that the 95th percentile estimate equals the TDI is regarded as
      both providing protection to highly exposed persons and leaving a reasonable
      margin of exposure relative to the TDI, then the chloroform drinking water
      criterion could be a concentration of 0.11mg/L. This implies a daily intake equal
      to 34% of the TDI allocated to the oral intake (2L/d) of drinking water for
      typical adults. For the highly exposed persons, inhalation exposure via
      evaporation from water contributed 53% of the total intake, whereas dermal
      absorption contributed only 3%. 

PMID- 23867355
TI  - Negative anion gap metabolic acidosis in salicylate overdose--a zebra!
AB  - Salicylate poisoning classically results in an increased anion gap metabolic
      acidosis. We discuss a case of normal anion gap metabolic acidosis despite
      elevated serum salicylate concentration. This diagnostic dilemma stemmed from
      aberrant reading of salicylate ions by analyzer electrodes as chloride ions
      leading to falsely negative anion gap. On review, this phenomenon is found to be
      possible with a number of commonly used analyzers. In emergency department
      settings, high level of clinical suspicion for salicylate poisoning should be
      maintained, and metabolic acidosis with normal anion gap should not be used to
      rule out salicylate overdose. This can prevent significant avoidable morbidity
      and mortality.

PMID- 23867356
TI  - Progressive multiple sclerosis: desperately seeking remedy.

PMID- 23867357
TI  - Clean unzipping by steam etching to synthesize graphene nanoribbons.
AB  - A simple, clean method of steam etching carbon nanotubes is reported for the
      synthesis of graphene nanoribbons. The chemical mechanism of carbon nanotube
      unzipping is also discussed. As an anode catalyst, as-prepared graphene
      nanoribbons combined with Pt exhibit quite a high catalytic activity for ethanol
      electro-oxidation in fuel cells. 

PMID- 23867358
TI  - Biphasic pro-melanogenic and pro-apoptotic effects of all-trans-retinoic acid
      (ATRA) on human melanocytes: time-course study.
AB  - BACKGROUND: The effects of retinoids on melanogenesis and their mechanism as
      depigmenting agents in topical therapy have not been fully elucidated.
      Conflicting data about their impact on melanogenic pathways have been reported.
      OBJECTIVE: To investigate the effects of all-trans-retinoic acid (ATRA) on normal
      human melanocytes from Caucasian subjects. METHODS: We assessed ATRA's
      cytotoxicity by measuring viability with a cell proliferation assay, and
      apoptotic effects using Annexin V and gamma-H2AX markers. ATRA's melanogenic
      activity was investigated based on spectrophotometric measurement of melanin
      content and tyrosinase enzymatic activity. Tyrosinase expression was assessed by
      Western blotting. We tested the antioxidant activity of superoxide dismutase
      (SOD) and catalase (CAT) in melanocytes using a spectrophotometric assay.
      RESULTS: Of the concentrations tested in this 72h time-course study, the 1.0MUM
      ATRA had a well-defined two-stage pro-melanogenic and pro-apoptotic effect on
      melanocytes. In the first 6h, treated cells showed significant increase (p<=0.01)
      of melanin content, tyrosinase, SOD, and CAT activities compared to the controls.
      While overall tyrosinase expression was not affected by ATRA, all other tested
      parameters decreased progressively beyond the short-term point of 6h. ATRA
      treatment of over 6h induced melanocyte apoptosis, as shown by the time-dependent
      decrease in cell viability, coupled with significant increase in Annexin V
      positive cells and nuclear accumulation of gamma-H2AX foci. CONCLUSION: The
      results obtained using this testing platform show a biphasic ATRA action:
      immediate pro-melanogenic effect and longer-term exposure pro-apoptotic activity.
      These data qualify ATRA as a potent tool to better understand the mechanisms that
      regulate the pigmentary system.

PMID- 23867359
TI  - High-level secretory expression of metchnikowin in Escherichia coli.
AB  - Metchnikowin is a proline-rich peptide from Drosophila with antibacterial and
      antifungal activities. Its commercial application is limited due to the low
      immune-inducible expression in vivo. Here we present a method to produce high
      yield metchnikowin in recombinant Escherichia coli. The genes coding for
      metchnikowin and the fusion partner Cherry tag were subcloned into the pET22b
      vector to construct a recombinant expression plasmid and transformed into E. coli
      BL21 (DE3). The fusion protein was successfully expressed and secreted with a
      yield of 300MUg/ml after 18-h induction. Active metchnikowin was released by
      cleavage of the Asp-Pro bond between fused proteins by 72-h formic acid
      hydrolysis at 50 degrees C. After 24-h dialysis, metchnikowin was purified to
      electrophoretic homogeneity and showed significant antibacterial activities
      against both Bacillus subtilis and E. coli DH5alpha. It is the first report on
      efficient production of metchnikowin in recombinant E. coli.

PMID- 23867360
TI  - Small structural differences of targeted anti-tumor toxins result in strong
      variation of protein expression.
AB  - Targeted anti-tumor toxins consist of a toxic functional moiety that is
      chemically linked or recombinantly fused to a cell-directing ligand. Ribosome
      inactivating proteins (RIPs), especially type I RIPs such as saporin or dianthin,
      are commonly used as toxin components. Although expression of type I RIP-based
      fusion proteins is well reported, the achievement of higher protein yields in
      heterologous expression systems through innovative strategies is of major
      interest. In the present study, the targeted toxins (his)saporin-EGF (SE) and
      (his)dianthin-EGF (DE) were expressed as fusion proteins under identical
      expression conditions. However, the total amount of DE was nearly two-times
      higher than SE. The identity of the heterologously expressed targeted toxins was
      confirmed by mass spectrometric studies. Their biological specific activity,
      monitored in real time, was almost equal. Sequence alignment shows 84% identity
      and a structural comparison revealed five major differences, two of which affect
      the secondary structure resulting in a loop (SE) to beta-strand (DE) conversion
      and one introduces a gap in SE (after position 57). In conclusion, these
      structural variations resulted in different protein expression levels while codon
      usage and toxicity to bacteria were excluded as a cause. Minor structural
      differences identified in this study may be considered responsible for the
      protection of DE from bacterial proteases and therefore may serve as a lead to
      modify certain domains in type I RIP-based targeted toxins.

PMID- 23867361
TI  - Kinetic characterization of arginine deiminase and carbamate kinase from
      Streptococcus pyogenes M49.
AB  - Streptococcus pyogenes (group A Streptococcus, GAS) is an important human
      pathogen causing mild superficial infections of skin and mucous membranes, but
      also life-threatening systemic diseases. S. pyogenes and other prokaryotic
      organisms use the arginine deiminase system (ADS) for survival in acidic
      environments. In this study, the arginine deiminase (AD), and carbamate kinase
      (CK) from S. pyogenes M49 strain 591 were heterologously expressed in Escherichia
      coli DH5alpha, purified, and kinetically characterized. AD and CK from S.
      pyogenes M49 share high amino acid sequence similarity with the respective
      enzymes from Lactococcus lactis subsp. lactis IL1403 (45.6% and 53.5% identical
      amino acids) and Enterococcus faecalis V583 (66.8% and 66.8% identical amino
      acids). We found that the arginine deiminase of S. pyogenes is not allosterically
      regulated by the intermediates and products of the arginine degradation (e.g.,
      ATP, citrulline, carbamoyl phosphate). The Km and Vmax values for arginine were
      1.13+/-0.12mM (mean+/-SD) and 1.51+/-0.07MUmol/min/mg protein. The carbamate
      kinase is inhibited by ATP but unaffected by arginine and citrulline. The Km and
      Vmax values for ADP were 0.72+/-0.08mM and 1.10+/-0.10MUmol/min/mg protein and
      the Km for carbamoyl phosphate was 0.65+/-0.07mM. The optimum pH and temperature
      for both enzymes were 6.5 and 37 degrees C, respectively.

PMID- 23867362
TI  - Improved PCR/nested PCR approaches with increased sensitivity and specificity for
      the detection of pathogens in hard ticks.
AB  - Most epidemiological studies on tick-borne pathogens employ PCR approaches.
      Prevalences determined by this method particularly depend on the efficiency and
      sensitivity of the applied protocol, which can be influenced by various factors.
      In the current study, we examined crucial points to improve PCR strategies with
      respect to sensitivity as well as specificity and developed optimized and easily
      practicable PCR/nested PCR approaches for the detection of different tick-borne
      pathogens. Among them were Anaplasma phagocytophilum, Borrelia burgdorferi sensu
      lato complex, and Babesia spp., for which the novel protocol was successfully
      applied to perform species determination by direct sequencing of PCR amplicons.
      The occurrence of double and multiple infections of different species of the same
      genus were detected by chromatogram analyses exhibiting mixed sequences.
      Furthermore, we suggest employing a standard plasmid containing the appropriate
      target sequence followed by verification of the encountered detection limit with
      an addition of tick DNA spiked with the appropriate pathogen DNA. Approaches
      standardized in this manner would facilitate the comparison of prevalence
      studies. 

PMID- 23867363
TI  - Simultaneous real-time PCR detection of Fusarium asiaticum, F. ussurianum and F.
      vorosii, representing the Asian clade of the F. graminearum species complex.
AB  - Due to the repeated discovery of new members of the Fusarium graminearum species
      complex (FGSC), some of the F. graminearum sensu stricto (s.s.)-specific qPCR
      assays developed to date have since been shown to be non-specific. In this study,
      a probe-based qPCR method was developed, targeting a sterol 14-alpha demethylase
      (CYP51) paralogue, CYP51C unique to the genus Fusarium, for the simultaneous
      detection of F. asiaticum, F. ussurianum and F. vorosii. Specificity of the assay
      was demonstrated for a wide range of Fusarium species, including all tested FGSC
      members (n=6), originating from different hosts and geographic regions. Alongside
      a previously published assay for detection of F. graminearum, we were able to
      show that members of the Asian clade of the FGSC (i.e. F. asiaticum, F.
      ussurianum and F. vorosii) were the primary etiological agent in wheat seeds
      samples originating from Central-East China. The grain samples from the UK tested
      negative for the presence of the FGSC's Asian clade and positive for presence of
      F. graminearum. It is likely that only F. graminearum s.s. is present in the UK,
      but the presence of other FGSC members cannot be ruled out and need further
      investigation. 

PMID- 23867364
TI  - Decontamination efficiency of high power ultrasound in the fruit and vegetable
      industry, a review.
AB  - Decontamination of fresh fruits and vegetables is an important unsolved
      technological problem. The main focus of this review is to summarize and
      synthesize the results of studies and articles about ultrasonic processing which
      can be adapted to the wash water decontamination process for fruits and
      vegetables. This review will also provide an overview about the importance of an
      effective wash water decontamination process in fruits and vegetables, the
      increase of foodborne outbreaks caused by fresh fruits and vegetables, microbial
      inactivation using ultrasound, and an interpretation of the high power ultrasound
      results in the fruits and vegetable industry. In addition, the limitations of
      ultrasonic processing in commercial applications have also been introduced. 

PMID- 23867365
TI  - Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients
      related to KCNJ2 mutation.
AB  - AIMS: Andersen-Tawil syndrome (ATS) is an uncommon form of channelopathy linked
      to mutations in the KCNJ2 gene. Currently, little is known about the long-term
      arrhythmic prognosis of this disease. METHODS AND RESULTS: We conducted a
      retrospective multicentre study in nine French hospitals. Patients were recruited
      only if they were KCNJ2 mutation carriers. Thirty-six patients (female n = 22,
      61%) from 20 unrelated kindred were included with a mean follow-up of 9.5 +/- 8.2
      years. We found 12 distinct KCNJ2 mutations in the 20 probands. Three of them
      were novel. Thirteen patients (36%) experienced syncope and one patient was
      resuscitated from cardiac arrest before diagnosis. The mean QTc interval was 439
      +/- 57 ms and QUc was 642 +/- 64 ms. All patients had normal ejection fraction.
      Holter recordings in 33 patients found 11 272 premature ventricular complexes
      (PVCs) per day on average, 25 patients had episodes of bigeminy, and 25 patients
      had polymorphic PVCs. Twenty-three patients (70%) had non-sustained polymorphic
      ventricular tachycardia (VT), and six sustained polymorphic VT. Only one patient
      presented with torsades de pointes. Patients were treated with beta-blocker (n =
      20), beta-blocker and amiodarone (n = 2), beta-blocker and flecainide (n = 6), or
      acetazolamide (n = 6). Radiofrequency ablation was attempted in five patients
      without clinical success. An implantable cardiac defibrillator was implanted in
      three patients. During follow-up, none of the patients died, four patients
      experienced syncope under treatment, and one patient had non-fatal cardiac
      arrest. CONCLUSION: Despite a severe clinical presentation with a very high rate
      of ventricular arrhythmias, the arrhythmic prognosis of the ATS patients is
      relatively good under treatment.

PMID- 23867366
TI  - Carbon dioxide insufflation during endoscopic retrograde
      cholangiopancreatography: a review and meta-analysis.
AB  - OBJECTIVES: The role of carbon dioxide (CO2) insufflation during endoscopic
      retrograde cholangiopancreatography (ERCP) is debated. A meta-analysis was
      performed to evaluate the efficacy and safety of CO2 insufflation for ERCP.
      METHODS: Searches were conducted in multiple databases composed of Pub-Medline,
      EMBASE, the Cochrane Library, science citation index expanded, Google scholar,
      and CNKI China series full-text database. Outcome measurements are listed below:
      ERCP procedural data, post-ERCP abdominal discomfort, radiographic evaluation of
      bowel gas volume, and CO2 safety data concerning CO2 elimination. RESULTS: Seven
      published randomized clinical trials involving 756 patients fulfilling the
      inclusion criteria were selected for meta-analysis, almost all of high quality.
      The incidence of ERCP-related complications was reduced by CO2 insufflation, so
      were the events of 1-hour, 3-hour, and 6-hour post-ERCP abdominal pain, based on
      their corresponding statistical results. Besides, CO2 insufflation was associated
      with less gas volume in the bowel lumen after the procedure. There were no
      significant differences between CO2 and air insufflation in total procedure time,
      the success rate of selective cannulation, post-ERCP abdominal distension,
      respectively. Subsequent sensitivity and subgroup analyses produced conflicting
      results. CONCLUSIONS: Compared with air insufflation, CO2 insufflation during
      ERCP reduces post-ERCP abdominal pain, post-ERCP bowel remnant gas volume, and
      ERCP-related complications, without clinically significant systematic CO2
      retention.

PMID- 23867367
TI  - Modest improvement in overall survival for patients with metastatic pancreatic
      cancer: a trend analysis using the surveillance, epidemiology, and end results
      registry from 1988 to 2008.
AB  - OBJECTIVES: Patients with pancreatic adenocarcinoma often present with distant
      metastatic disease. We aimed to assess whether improvements in survival of
      clinical trials translated to a population-based level. METHODS: The US
      Surveillance, Epidemiology, and End Results registry was queried. Adult patients
      with distant metastatic adenocarcinoma of the pancreas were included from 1988 to
      2008. Overall survival was analyzed using Kaplan-Meier curves as well as
      multivariable-adjusted Cox proportional hazards models. RESULTS: In total, 32,452
      patients were included. Mean age was 67.6 (SD: 11.7) years, and 15,341 (47.3%)
      were female. Median overall survival was 3 months (95% confidence interval [CI],
      3-3 months), which increased from 2 (CI, 2-2) months in 1988 to 3 (CI, 3-4)
      months in 2008. After adjustment for multiple covariates, the hazard ratio (HR)
      decreased by 0.977 per year (CI, 0.975-0.980). In multivariable-adjusted survival
      analyses, tumor location in the pancreatic body/tail (HR, 1.10), male sex (HR,
      1.09), increasing age (HR, 1.016), African American ethnicity (HR, 1.16),
      nonmarried civil status (HR, 1.18), and absence of radiotherapy (HR, 1.41) were
      associated with worse survival (P < 0.001 for all predictors). CONCLUSIONS: The
      improvement in overall survival over the past 2 decades among patients with
      metastatic pancreatic adenocarcinoma is modest and disappointing. More effective
      therapeutic strategies for advanced disease are desperately needed.

PMID- 23867369
TI  - Electrosurgical generators.

PMID- 23867370
TI  - Tissue adhesives: cyanoacrylate glue and fibrin sealant.

PMID- 23867372
TI  - VideoGIE - launch!

PMID- 23867371
TI  - Endoscopic mucosal tissue sampling.

PMID- 23867373
TI  - Esophageal strictures after extensive endoscopic resection: hope for a better
      outcome?

PMID- 23867374
TI  - What we want for ESD is a second hand! Traction method.

PMID- 23867375
TI  - How to review.

PMID- 23867376
TI  - Endoscopic diagnosis of celiac disease: what is the role of capsule endoscopy?

PMID- 23867377
TI  - AIMS65 score predicts short-term mortality but not the need for intervention in
      acute upper GI bleeding.

PMID- 23867378
TI  - Response.

PMID- 23867379
TI  - Percutaneous balloon dilation and placement of endoscopic biliary stent by using
      the double-balloon enteroscopy ERCP rendezvous technique.

PMID- 23867380
TI  - From the pathologist: review of sexual behaviors should be a routine component of
      clinical histories.

PMID- 23867381
TI  - Prophylactic clip closure.

PMID- 23867382
TI  - Response.

PMID- 23867383
TI  - Predictors of provider-patient visit frequency during hemodialysis.
AB  - BACKGROUND/AIMS: In 2004, the Centers for Medicare and Medicaid Services tied
      reimbursement for outpatient hemodialysis services to the number of times per
      month providers see their dialysis patients, resulting in increased provider
      patient visit frequency. Greater provider-patient visit frequency is associated
      with lower hospitalization risk for hemodialysis patients, and determinants of
      visit frequency are uncertain. We aimed to identify patient, provider, and
      dialysis facility characteristics associated with provider visit frequency.
      METHODS: This retrospective cohort study used United States Renal Data System
      (USRDS) data for point-prevalent patients receiving in-center hemodialysis on
      January 1, 2006 (n = 144,860). Patient characteristics were defined from January
      1 to June 30, 2006, and provider-patient visit frequency (<4 vs. >=4
      visits/month) from July 1 to December 31, 2006. Patient characteristics were
      obtained from the USRDS. Provider data were obtained from the American Medical
      Association Physician Master File. We determined longitudinal associations
      between patient, provider, and facility characteristics and provider-patient
      visit frequency using logistic regression. RESULTS: Patient characteristics
      independently associated with greater provider-patient visit frequency included
      older age, African-American race, longer dialysis duration, higher comorbidity
      score, Medicaid eligibility, urban residence, better compliance with dialysis,
      and more hospital days during run-in. Provider characteristics associated with
      greater provider-patient visit frequency included more years in practice,
      graduation from a foreign medical school, shorter distance between provider
      office and dialysis unit, and caring for more dialysis patients; facility
      characteristics included free-standing, independent status. CONCLUSION: After the
      Medicare reimbursement policy change, several patient, provider, and facility
      characteristics were independently associated with greater dialysis provider
      patient visit frequency.

PMID- 23867384
TI  - Diffuse alveolar hemorrhage due to ketorolac tromethamine.
AB  - Drug-induced lung disease (DILD) is a common but frequently missed diagnosis.
      Therefore, a high index of clinical suspicion and familiarity with the clinical
      syndromes associated with DILD are important in making the diagnosis.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the mostly commonly used
      classes of medications. NSAIDs are safe when used at prescribed doses. Side
      effects from use of NSAIDs are not uncommon and can affect almost every organ
      system in the body. NSAIDs are notorious for causing pulmonary toxicity, the
      common ones being bronchospasm and hypersensitivity reactions. Diffuse alveolar
      hemorrhage (DAH) secondary to NSAIDs is uncommon. Here, we report a case of DAH
      secondary to the use of ketorolac tromethamine. 

PMID- 23867385
TI  - Design and synthesis of 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one
      derivatives as novel anticancer agents that induce apoptosis with cell cycle
      arrest at G2/M phase.
AB  - Novel 6,7-methylenedioxy-4-substituted phenylquinolin-2(1H)-one derivatives 12a-n
      were designed and prepared through an intramolecular cyclization reaction and
      evaluated for in vitro anticancer activity. Among the synthesized compounds, 6,7
      methylenedioxy-4-(2,4-dimethoxyphenyl)quinolin-2(1H)-one (12e) displayed potent
      cytotoxicity against several different tumor cell lines at a sub-micromolar
      level. Furthermore, results of fluorescence-activated cell sorting (FACS)
      analysis suggested that 12e induced cell cycle arrest in the G2/M phase
      accompanied by apoptosis in HL-60 and H460 cells. This action was confirmed by
      Hoechst staining and caspase-3 activation. Due to their easy synthesis and
      remarkable biological activities, 4-phenylquinolin-2(1H)-one analogs (4-PQs) are
      promising new anticancer leads based on the quinoline scaffold. Accordingly,
      compound 12e was identified as a new lead compound that merits further
      optimization and development as an anticancer candidate. 

PMID- 23867386
TI  - In search of potent and selective inhibitors of neuronal nitric oxide synthase
      with more simple structures.
AB  - In certain neurodegenerative diseases damaging levels of nitric oxide (NO) are
      produced by neuronal nitric oxide synthase (nNOS). It, therefore, is important to
      develop inhibitors selective for nNOS that do not interfere with other NOS
      isoforms, especially endothelial NOS (eNOS), which is critical for proper
      functioning of the cardiovascular system. While we have been successful in
      developing potent and isoform-selective inhibitors, such as lead compounds 1 and
      2, the ease of synthesis and bioavailability have been problematic. Here we
      describe a new series of compounds including crystal structures of NOS-inhibitor
      complexes that integrate the advantages of easy synthesis and good biological
      properties compared to the lead compounds. These results provide the basis for
      additional structure-activity relationship (SAR) studies to guide further
      improvement of isozyme selective inhibitors. 

PMID- 23867387
TI  - Design, synthesis and structure-activity relationships of some novel, highly
      potent anti-invasive (E)- and (Z)-stilbenes.
AB  - In our ongoing exploration of the structure-activity landscape of anti-invasive
      chalcones, we have prepared and evaluated a number of structurally related (E)-
      and (Z)-stilbenes. These molecules exhibited an extraordinary high in vitro
      potency in the chick heart invasion assay, being active up to 10nmolL(-1), a
      concentration level a 100-fold lower than the lowest effective doses that have
      been reported for natural analogues. Furthermore, they possess an interesting
      pharmacological profile in silico. 

PMID- 23867388
TI  - Catalytic asymmetric total synthesis of (S)-(-)-zearalenone, a novel lipoxygenase
      inhibitor.
AB  - A catalytic asymmetric synthesis of (S)-(-)-zearalenone is reported using
      asymmetric allylic alkylation for the introduction of the stereocenter. (S)-(-)
      Zearalenone turned out to be a novel lipoxygenase inhibitor. 

PMID- 23867389
TI  - Carbonic anhydrase inhibitors: Synthesis and inhibition of the cytosolic
      mammalian carbonic anhydrase isoforms I, II and VII with benzene sulfonamides
      incorporating 4,5,6,7-tetrachlorophthalimide moiety.
AB  - A series of 4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl benzenesulfonamide
      derivatives (compounds 1-8) was synthesized by reaction of benzene sulfonamides
      incorporating primary amino moieties with 4,5,6,7-tetrachlorophthalic anhydride.
      These sulfonamides were assayed as inhibitors of the metalloenzyme carbonic
      anhydrase (CA, EC 4.2.1.1). Some of these compounds showed very good in vitro
      human carbonic anhydrase (hCA) isoforms I, II and VII inhibitory properties, with
      affinities in the low nanomolar range. Inhibition activities against hCA I were
      in the range of 159-444nM; against hCA II in the range of 2.4-4515nM, and against
      hCA VII in the range of 1.3-469nM. The structure-activity relationship (SAR) with
      this series of sulfonamides is straightforward, with the main features leading to
      good activity for each isoform being established. 

PMID- 23867390
TI  - Evaluation of novel aryloxyalkyl derivatives of imidazole and 1,2,4-triazole as
      heme oxygenase-1 (HO-1) inhibitors and their antitumor properties.
AB  - A novel series of aryloxyalkyl derivatives of imidazole and 1,2,4-triazole, 17
      31, was designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and
      heme oxygenase-2 (HO-2). Some of these compounds were found to be good inhibitors
      of HO-1, in particular those carrying an imidazole moiety as azolyl group and a 3
      bromo or 4-iodophenyl as aryl moiety. The most potent compounds 6 and 30 were
      selected and studied for their antitumor properties in a model of LAMA-84 R cell
      line overexpressing HO-1 and resistant to imatinib mesylate (IM), a tyrosine
      kinase inhibitor used in the treatment of multiple types of cancer, most notably
      Philadelphia Chromosome positive (Ph(+)) Chronic Myelogenous Leukemia (CML).
      Results show that both 6 and 30 sensitized LAMA-84 R cell line to antitumor
      properties of IM. 

PMID- 23867391
TI  - Downregulation of EIF4A2 in non-small-cell lung cancer associates with poor
      prognosis.
AB  - BACKGROUND: EIF4A2, which belongs to the eukaryotic initiation factor 4A family,
      is a highly conserved gene for one of the protein-synthesis initiation factors
      involved in the binding of messenger RNA to the ribosome. The role of EIF4A2 in
      some cancers, eg, breast cancer and melanoma, has been studied. However, the
      clinical significance and biologic role of EIF4A2 in lung cancer remains unknown.
      PATIENTS AND METHODS: A total of 170 patients with non-small-cell lung cancer who
      were undergoing surgical resection were studied. We applied the tissue microarray
      by using immunohistochemistry to study the expression of EIF4A2 in patients with
      non-small-cell lung cancer (NSCLC). RESULTS: We found that the expression rate of
      EIF4A2 in NSCLC was 87.6%. The expression of EIF4A2 was significantly correlated
      with the histopathologic classification (P = .049) and tumor grade (P < .019).
      Moreover, NSCLC patients with low EIF4A2 expression survived shorter than those
      with high EIF4A2 expression, as indicated by overall survival (P = .023) and
      disease-free survival (P = .011) assessed by the Kaplan-Meier method. In
      addition, multivariate analysis suggested EIF4A2 as an independent predictor of
      disease-free survival (hazard ratio 0.543 [95% CI, 0.329-0.897]; P = .017).
      CONCLUSION: Collectively, our study demonstrated that EIF4A2 was remarkably
      involvement in the development of NSCLC and could be served as a potential
      prognostic marker for patients with this deadly disease.

PMID- 23867392
TI  - Enhanced cellulose orientation analysis in complex model plant tissues.
AB  - The orientation distribution of cellulose microfibrils in the plant cell wall is
      a key parameter for understanding anisotropic plant growth and mechanical
      behavior. However, precisely visualizing cellulose orientation in the plant cell
      wall has ever been a challenge due to the small size of the cellulose
      microfibrils and the complex network of polymers in the plant cell wall. X-ray
      diffraction is one of the most frequently used methods for analyzing cellulose
      orientation in single cells and plant tissues, but the interpretation of the
      diffraction images is complex. Traditionally, circular or square cells and
      Gaussian orientation of the cellulose microfibrils have been assumed to elucidate
      cellulose orientation from the diffraction images. However, the complex tissue
      structures of common model plant systems such as Arabidopsis or aspen (Populus)
      require a more sophisticated approach. We present an evaluation procedure which
      takes into account the precise cell geometry and is able to deal with complex
      microfibril orientation distributions. The evaluation procedure reveals the
      entire orientation distribution of the cellulose microfibrils, reflecting
      different orientations within the multi-layered cell wall. By analyzing aspen
      wood and Arabidopsis stems we demonstrate the versatility of this method and show
      that simplifying assumptions on geometry and orientation distributions can lead
      to errors in the calculated microfibril orientation pattern. The simulation
      routine is intended to be used as a valuable tool for nanostructural analysis of
      plant cell walls and is freely available from the authors on request. 

PMID- 23867393
TI  - High-resolution scanning electron microscopy of the cytoskeleton of
      Tritrichomonas foetus.
AB  - Tritrichomonas foetus is a pathogenic protozoan that causes bovine
      trichomoniasis. In addition to its importance in veterinary medicine, this
      parasite is also a good representative of one the earliest eukaryotic cells
      available for study. T. foetus contains organelles that are common to all
      eukaryotic cells as well as uncommon cell structures such as hydrogenosomes and a
      complex and elaborate cytoskeleton that constitutes the mastigont system. The
      mastigont system is mainly formed by several proteinaceous structures that are
      associated with basal bodies, the pelta-axostylar complex and the costa. Although
      the structural organization of trichomonad cytoskeletons has been analyzed using
      several techniques, observation using a new generation of scanning electron
      microscopes with a resolution of 0.8nm has allowed more detailed visualization of
      the three-dimensional organization of the mastigont system. Moreover, this study
      revealed the presence of new structures, such as the costa accessory filament,
      and the presence of two groups of microtubules that form the pelta-axostylar
      system. 

PMID- 23867394
TI  - The role of cultural transmission in human demographic change: an age-structured
      model.
AB  - Human populations vary demographically with population sizes ranging from small
      groups of hunter-gatherers with less than fifty individuals to vast cities
      containing many millions. Here we investigate how the cultural transmission of
      traits affecting survival, fertility, or both can influence the birth rate, age
      structure, and asymptotic growth rate of a population. We show that the strong
      spread of such a trait can lead to a demographic transition, similar to that
      experienced in Europe in the late 19th and early 20th centuries, without using
      ecological or economic optimizing models. We also show that the spread of a
      cultural trait that increases fertility, but not survival, can cause demographic
      change similar to the 'Neolithic demographic transition': a period of increased
      population growth that is thought to have accompanied the transition from hunter
      gatherer to agricultural lifestyles. We investigate the roles of vertical,
      oblique, and horizontal learning of such a trait in this transition and find that
      compared to vertical learning alone, horizontal and oblique learning can
      accelerate the trait's spread, lead to faster population growth, and increase its
      equilibrium frequency. 

PMID- 23867396
TI  - Neurobehavioural disorders after traumatic brain injury: assessment, treatment
      and outcome.

PMID- 23867395
TI  - Liver X receptor alpha inhibits osteosarcoma cell proliferation through up
      regulation of FoxO1.
AB  - BACKGROUND: Osteosarcoma is the most common primary bone malignancy of
      adolescents and young adults. METHODS: We analyzed liver X receptor alpha
      (LXRalpha) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent
      noncancerous tissues. Moreover, we investigated LXRalpha's potential role in
      regulating cell proliferation in Saos-2 and U2OS cells. RESULTS: We found that
      activation of LXRalpha, a member of nuclear receptor, was able to inhibit cell
      proliferation in Saos-2 and U2OS cells. At the molecular level, our results
      further revealed that expression of tumor suppressor gene, FoxO1, was up
      regulated by LXRalpha activation. LXRalpha activates FoxO1 transcription through
      a direct binding on its promoter region. CONCLUSION: LXRalpha acts as a tumor
      suppressor for osteosarcoma, which may offer a new way in molecular targeting
      cancer treatment.

PMID- 23867397
TI  - Recognising and assessing neurobehavioural disability after traumatic brain
      injury.
AB  - BACKGROUND: Neurobehavioural disability often leads to serious social handicap.
      Many individuals never recover full social independence and will remain largely
      dependent upon family support, imposing a significant and potentially life-long
      psychological burden on those who care for injured relatives. Close relationships
      are at risk and many partnerships break down, increasing the risk of social
      isolation and subsequent psychological distress to the survivor. OBJECTIVES: The
      aim of this paper is to examine the nature of some cardinal features of
      neurobehavioural disability that contribute to poor psychosocial outcome;
      consider their organic origins, and problems associated with standardised methods
      of assessment. METHODS: A review of clinical literature addressing
      neurobehavioural disability after TBI. RESULTS: Many forms of neurobehavioural
      disability are subtle but have a pervasive impact on psychosocial outcome in
      general and relationships in particular. CONCLUSIONS: Caution is recommended when
      employing standardised tests to identify the complex and often subtle nature of
      neurobehavioural disorders. More work is needed to define the nature and impact
      of different forms of neurobehavioural disorders that comprise this complex form
      of disability.

PMID- 23867398
TI  - Neuroimaging and social behavior in children after traumatic brain injury:
      findings from the Social Outcomes of Brain Injury in Kids (SOBIK) study.
AB  - BACKGROUND: Neuroimaging studies identified either focal and/or non-specific
      frontotemporolimbic damage resulting from mild-complicated to severe traumatic
      brain injury (TBI) in a subset of 12 children 8-12 years of age who were part of
      the Social Outcomes of Brain Injury in Kids (SOBIK) study. The influence of
      identifiable damage on social behavior was examined. METHODS: Magnetic resonance
      imaging was obtained on average 2.5 years post injury wherein cases with distinct
      abnormalities were selected. Various direct, performance-based measures of
      cognitive-social-emotional functioning were obtained along with data regarding
      peer relations and friendships in the classroom. RESULTS: Overall, children with
      TBI were impaired on tasks of social-emotional processing compared to children
      with orthopedic injury (OI). Ten of the 12 children with TBI had multiple areas
      of impaired social-emotional functioning in comparison to OI controls. With
      regards to friendships, four of the nine children with TBI who had classroom data
      had no mutual friends, four also received low peer acceptance ratings, and two
      were perceived by peers as having high levels of rejection/victimization in the
      classroom. CONCLUSIONS: Children with frontotemporolimbic or diffuse damage
      demonstrated variable social outcomes from their TBI. Results are discussed in
      terms of the heterogeneity of TBI-related abnormalities and their relationship to
      social behavior.

PMID- 23867399
TI  - Obstacles to remediating coping following traumatic brain injury.
AB  - BACKGROUND: Coping has been suggested as the final common pathway related to
      outcome after traumatic brain injury (TBI). Different types of coping have been
      related to either positive or negative psychosocial outcomes. As a result, a
      small set of studies have attempted to remediate coping through intervention, but
      the effectiveness of these studies has been modest. CONCLUSION: We propose that
      three primary factors are limiting our ability to effectively remediate coping
      following TBI through intervention TBI: 1) limited understanding of inter-patient
      variability following TBI; 2) limited understanding of the mechanisms underlying
      coping following TBI; and 3) reliance on self-report measures of coping. We
      discuss these obstacles in the context of a model of frontal lobe function, and
      in light of recent behavioural work on coping.

PMID- 23867400
TI  - A systematic review of assessment tools for adults used in traumatic brain injury
      research and their relationship to the ICF.
AB  - BACKGROUND AND AIMS: Good assessment is an essential component of effective
      patient management. Yet the sheer volume of available assessment instruments
      presents a barrier for the clinician or researcher to (a) be knowledgeable about
      suitable measures and (b) keep up-to-date with new measures that are published.
      In order to create a resource of currently-used measures, we conducted a
      systematic review of assessment tools used in the research literature on
      traumatic brain injury (TBI). METHODS: We used two electronic databases (Medline
      and PsycINFO) to identify full-length, English-language articles published
      between 2000 and 2012 in which outcome in adults with TBI was assessed with
      behavioural tests or questionnaires. RESULTS: The searches yielded 5,735 articles
      and after deletion of duplicates (n = 1,383) and articles not meeting selection
      criteria (n = 1,759), 2,593 articles were further examined. The articles
      contained 910 behavioural instruments, with a final set of 728 unique
      instruments. Each instrument was classified against the International
      Classification of Functioning, Disability and Health (ICF). Half of the
      instruments (n = 370, 50.8%) evaluated the mental functions domain of the ICF
      body functions component, with a substantially smaller proportion (n = 64, 8.8%)
      examining specific motor-sensory and other body functions. Instruments also
      covered domains of activities/participation (n = 109, 15.0%), environmental
      factors (n = 22, 3.0%) and personal factors (n = 36, 4.9%). A substantial number
      of scales (n = 93, 12.8%) were multidimensional across the body function domains
      (n = 32), as well as the functioning and disability part of the ICF (n = 60). The
      remaining 5% of instruments addressed concepts not covered by the ICF, including
      quality of life (n = 19, 2.6%) and rehabilitation process tools (such as
      therapeutic alliance). The 728 instruments were listed and more than 70 of the
      most common, spread across 20 domains, were highlighted. CONCLUSION: These data
      provide a comprehensive and up-to-date resource that gives the researcher or
      clinician a very large selection of assessment instruments covering the major
      areas of function pertinent to TBI.

PMID- 23867401
TI  - Challenges and opportunities facing holistic approaches to neuropsychological
      rehabilitation.
AB  - BACKGROUND: Holistic approaches to neuropsychological rehabilitation have
      progressively been recognized as an important form of rehabilitative care for
      persons who have a history of moderate to severe traumatic brain injury.
      OBJECTIVE: After providing historical and contemporary perspectives, identify
      challenges and opportunities facing the field of neuropsychological
      rehabilitation. METHODS: Selective literature review from neuropsychological
      rehabilitation, neurosciences, learning theory, cognitive neuropsychology, and
      psychotherapy that highlight challenges to the development of holistic
      neuropsychological rehabilitation. RESULTS: Ten challenges and associated
      opportunities that face the field of holistic neuropsychological rehabilitation
      are identified. Illustrations of these challenges and opportunities are provided.
      CONCLUSIONS: Effectively addressing the challenges that face holistic
      neuropsychological rehabilitation will result in greater advances for this field
      of care for both children and adults.

PMID- 23867402
TI  - Neurobehavioural approaches to the rehabilitation of challenging behaviour.
AB  - BACKGROUND: Neurobehavioural disability (NBD) following acquired brain injury
      undermines capacity for independent social behaviour and results in serious long
      term social handicap. The presence of challenging behaviour as a feature of NBD
      has obvious implications for rehabilitation and community reintegration.
      OBJECTIVES: Behavioural approaches are seen by many as fundamental to the
      successful rehabilitation of challenging behaviour. This paper will a) define the
      nature of neurobehavioural rehabilitation; b) explore the characteristics of
      cases referred, and c) the outcomes achieved. Strengths, limitations and future
      developments of neurobehavioural approaches for challenging behaviour will be
      considered along with potential factors that limit generalisation and longevity
      of treatment gains. METHODS: Literature review. RESULTS: Neurobehavioural
      services are distinguishable from other forms of neurorehabilitation. There is
      considerable evidence supporting the central role of both positive behaviour
      supports and contingency management approaches in creating conditions that
      minimise neurocognitive impairment, facilitate new learning, and ensure a
      positive social climate in both specialised inpatient units and community
      settings. Possible limitations include over-reliance on evidence from successful
      accounts of single cases and lack of knowledge regarding generalisation.
      CONCLUSIONS: Neurobehavioural rehabilitation is effective and can save care costs
      in the long term. More evidence regarding maintenance of gains is required.

PMID- 23867403
TI  - Selecting the appropriate psychotherapies for individuals with traumatic brain
      injury: what works and what does not?
AB  - BACKGROUND: When traditional psychotherapy is provided to patients with traumatic
      brain injuries (TBIs), the primary focus is on treating mood changes such as
      depression, anxiety or anger. However, traditional psychotherapeutic methods
      developed specifically for mood changes fall short when treating most TBI
      patients. In large part, this is because the psychological adjustment
      difficulties that most TBI patients face are linked to life-altering changes that
      are interwoven with permanent physical, cognitive, and social sequelae. In
      addition, mood changes in TBI patients are also caused by vocational and
      financial losses. OBJECTIVE: The sudden onset of these unfamiliar and
      interdependent problems necessitates a psychotherapeutic approach that
      acknowledges the inherent challenges of coping with multiple life-altering
      changes. For patients who experience a shattered sense of self, interventions
      need to be explored to make life meaningful following a TBI. METHODS: An
      existentially-oriented approach is introduced in the following steps: (1)
      identifying pre-injury future expectations, (2) examining how the TBI has altered
      these expectations, (3) grieving the loss of the expected future, and (4)
      developing a realistic future that is existentially meaningful. RESULTS: Pivotal
      gains are achieved when patients rebuild their lives according to their own core
      values. CONCLUSION: TBI patients can benefit from existential psychotherapy.

PMID- 23867404
TI  - Cost effective ways of facilitating home based rehabilitation and support.
AB  - BACKGROUND: The long term support of people with neurobehavioural disorders
      following a severe traumatic brain injury (TBI) can amount to a lifetime cost of
      several million dollars. Such costs are often obtained from personal injury
      compensation. However, those not eligible for such awards often depend on their
      families to provide support and care at no direct financial cost, but with
      indirect financial and human costs in terms of loss of productivity, and
      increased stress and health problems. OBJECTIVES: The aim of this paper is to
      examine the role of support workers in the long-term care of those with
      neurobehavioural deficits following severe TBI and to discuss the feasibility of
      meeting some aspects of their role with technological solutions. METHODS: This
      critical review uses observational and cost-analysis methodologies to establish
      the roles and costs associated with staff supporting people with neurobehavioural
      disorders resulting from severe TBI. RESULTS: The role of support workers is
      varied and includes prompting to initiate and guide simple or complex activities,
      promoting social behaviour and managing emotional reactions. Some of these roles
      can be fulfilled by existing technology. CONCLUSIONS: Cost effective care of
      those with long-term neurobehavioural disorders can be provided by a combination
      of human support and existing technology.

PMID- 23867405
TI  - Outcome of rehabilitation for neurobehavioural disorders.
AB  - BACKGROUND: The evidence base on neurobehavioural disorders and their
      rehabilitation has been growing for four decades. Over that time understanding of
      the need for effective interventions for a range of handicaps in personal,
      interpersonal and employment spheres has developed. There is a continuing need to
      demonstrate whether interventions, are effective and cost-sensitive. Moreover, in
      pursuing effectiveness, clinicians need to be able to predict which individuals
      are likely to benefit from a programme and here, clinical experience needs to be
      informed by research evidence. OBJECTIVE: To review the outcome of rehabilitation
      for neurobehavioural disorders. METHODS: This review initially considers the
      background to neurobehavioural rehabilitation and discusses methodological
      issues. It reviews the evidence for neurobehavioural interventions for severe
      head injury with emphasis on holistic models of care, behavioural treatments,
      interventions in non-specialist settings and for emotion perception and self
      awareness. RESULTS: In general, there is a need for further high quality studies
      with longer follow-ups and evidence for generalisation in the community. However,
      there is a growing consensus that intensive holistic rehabilitation programmes
      can improve community reintegration and self-efficacy. For behaviour disturbance
      the evidence base largely comprises studies with weaker (single group or single
      case) designs. Overall studies here provide limited evidence in support of
      behavioural approaches for externalised behaviour such as aggression. Further RCT
      or group comparison studies are needed. In terms of negative behaviours such as
      apathy, there are few studies on head injury and conclusions cannot be made with
      confidence. Self awareness is a key issue associated with good outcome in general
      and research to date supports use of interventions that focus in on-task
      behaviour and education. The correct perception of emotions in others is a
      precursor to successful social interaction, and here there is very little
      evidence although early studies are encouraging. CONCLUSION: There is mounting
      evidence to support the effectiveness of non-pharmacological interventions for
      neurobehavioural disorders. Successful outcomes are often associated with
      intensive and prolonged interventions involving multidisciplinary working.

PMID- 23867406
TI  - Factors contributing to outcome following traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury results in some distinctive patterns of
      cognitive, behavioural and physical impairment which impact significantly on
      independent living skills and participation in work or study, social and leisure
      activities and interpersonal relationships. There is, however, still considerable
      variability in outcome across individuals in each of the reported domains. This
      has led to a significant body of research examining factors associated with
      outcome. A range of injury-related, personal and social factors have been shown
      to influence survival, as well as cognitive, functional and employment outcome.
      METHODS: This paper reviews the factors associated with each of these aspects of
      outcome specifically injury-related factors, including neuroimaging findings, GCS
      and PTA, other injuries, and cognitive and behavioural impairments; demographic
      factors, including age, gender, genetic status, education, pre-injury IQ and
      employment status; and social factors including family and other social support,
      cultural factors, pre-injury psychiatric history and coping style. CONCLUSION:
      The paper identifies contributions and complex interrelationships of all of these
      factors to outcome following TBI. It concludes with a brief discussion of the
      implications of these factors for the rehabilitation process.

PMID- 23867407
TI  - Quality of patient education materials for rehabilitation after neurological
      surgery.
AB  - OBJECTIVE: To evaluate the quality of online patient education materials for
      rehabilitation following neurological surgery. METHODS: Materials were obtained
      from the National Institute of Neurological Disorders and Stroke (NINDS), U.S.
      National Library of Medicine (NLM), American Occupational Therapy Association
      (AOTA), and the American Academy of Orthopaedic Surgeons (AAOS). After removing
      unnecessary formatting, the readability of each site was assessed using the
      Flesch Reading Ease and Flesch-Kincaid Grade Level evaluations with Microsoft
      Office Word software. RESULTS: The average values of the Flesch Reading Ease and
      Flesch-Kincaid Grade Level were 41.5 and 11.8, respectively, which are well
      outside the recommended reading levels for the average American. Moreover, no
      online section was written below a ninth grade reading level. CONCLUSION:
      Evaluations of several websites from the NINDS, NLM, AOTA, and AAOS demonstrated
      that their reading levels were higher than that of the average American. Improved
      readability might be beneficial for patient education. Ultimately, increased
      patient comprehension may correlate to positive clinical outcomes.

PMID- 23867408
TI  - Inhibition of monitoring mechanisms in response to erroneous or veridical
      feedback. "Virtual lesion" induction by an rTMS study.
AB  - External feedback from contextual cues allows humans to behave appropriately in
      their environments. In the present study, the explicit process of feedback
      monitoring (an explicit response to veridical vs false feedback) was explored. In
      addition, the contribution of the prefrontal cortex in this monitoring process
      was tested by administering an rTMS inhibitory paradigm. Seventeen subjects
      participated in the study and were required to detect correct vs. incorrect
      feedback. The experimental task included three main phases: the subject's
      performance (spatial decisional task); the system's response to the performance
      (external feedback); and the subject's judgment and response to this external
      feedback (feedback monitoring). rTMS was performed on the DLPFC. As shown by the
      behavioural measures (error rate and response times), DLPFC deactivation induced
      worse performance (higher ER and RT) for both correct and incorrect feedback.
      Indeed, this prefrontal region seems to contribute to conscious monitoring
      functions when an explicit response is required. Possible applications to
      executive function analysis and rehabilitation are suggested. 

PMID- 23867409
TI  - Immediate effect of Walkbot robotic gait training on neuromechanical knee
      stiffness in spastic hemiplegia: a case report.
AB  - PURPOSE: The purpose of this study was to investigate the immediate effect of
      Walkbot gait training on knee joint stiffness in an individual with spastic
      hemiplegia. METHOD: A woman with hemiparetic stroke underwent a 30-minute Walkbot
      robotic-assisted gait training session. Knee flexion stiffness associated with
      hamstring spasticity and knee extension torques during the terminal swing phase
      was determined before and after the intervention using the Walkbot-STIFF
      measurement system. DESIGN: Descriptive case analysis. RESULTS: Knee joint
      extension kinematic at the terminal swing phase increased from 2.44 degrees  to 
      0.28 degrees . Knee joint torque increased from 0.26 Nm to 0.32 Nm. The knee
      flexion stiffness decreased from 0.0083 Nm/degree to 0.0022 Nm/degree following
      the training. CONCLUSIONS: The Walkbot robotic-assisted locomotor training was
      effective for reducing knee joint stiffness and improving extensor torque during
      functional gait. Moreover, the Walkbot-STIFF system was useful for assessing and
      monitoring spasticity during locomotor training.

PMID- 23867410
TI  - Aftereffect induced by prisms of different power in the rehabilitation of
      neglect: A multiple single case report.
AB  - OBJECTIVES: Prism Adaptation (PA) is a technique used in the rehabilitation of
      unilateral spatial neglect. Several researchers have reported positive results on
      a number of tasks, but negative outcomes have also been reported. These
      conflicting results could be due to the use of prisms of different power. The aim
      of this study was to investigate the amplitude and duration of the aftereffect
      induced by prisms of different power by different measures in a series of single
      cases of neglect. METHODS: Five neglect patients and ten control subjects
      participated in the study. Prism adaptation was evaluated with Subjective
      Straight Ahead (SSA), Open-Loop Pointing (OLP) and Line Bisection (LB) tasks,
      immediately before prism adaptation, immediately after, and 10/60 minutes after
      prism adaptation. The procedure was repeated with prisms of 5, 10 and 20
      prismatic diopters (Delta). RESULTS: The OLP task provided the most sensitive
      measures for the size of the aftereffect. The 20Delta prism proved to be most
      effective in inducing an immediate aftereffect, while the aftereffect of the
      5Delta prism seemed to last longer. CONCLUSION: We showed that the prism power
      and the task used for assessing PA effect are relevant variables to be consider
      in clinical practice of neglect rehabilitation.

PMID- 23867411
TI  - Combined rehabilitation program for postural instability in progressive
      supranuclear palsy.
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) is an atypical parkinsonism
      clinically characterized by prominent axial extrapyramidal motor symptoms with
      frequent falls. The clinical response to L-dopa is poor and there is strong need
      for alternative treatment strategies. METHODS: We tested the efficacy of a
      rehabilitative program combining a dynamic antigravity postural system (SPAD) and
      a vibration sound system (ViSS) on postural instability of 10 patients affected
      by PSP. The patients underwent SPAD and VISS treatments with a 3 sessions/week
      schedule for 2 months. Patients were clinically examined at baseline, every week
      during the 2-months treatment, and at 1 month after the end of treatment for the
      following parameters: baropodometry static, baropodometry dynamic and
      stabilometry. PSP rating scale and PD36 quality of life scale were also
      administered. RESULTS: The combined rehabilitative program produced improvement
      of all the parameters explored (p = 0.01-0.05) at the end of treatment as
      compared to baseline. Baropodometric dynamics improvement lasted until the end of
      follow-up. CONCLUSION: Our results suggest that a specific rehabilitation program
      could improve postural instability in PSP patients. A more continuous treatment
      protocol would allow stabilizations of results.

PMID- 23867412
TI  - The cortical activation differences between proximal and distal joint movements
      of the upper extremities: a functional NIRS study.
AB  - OBJECTIVES: Motor control of musculature of proximal and distal joints has been
      suggested to differ. However, no study comparing patterns of activation between
      movements of proximal and distal joints has been conducted. In this study, using
      functional near infrared spectroscopy (fNIRS), we attempted to compare patterns
      of cortical activation generated during movements of shoulder and hand. METHODS:
      Nine normal subjects were recruited. fNIRS was performed using a fNIRS system
      with 49 channels. Flexion-extension movements of the right shoulder or hand were
      performed. We measured values of oxy-hemoglobin (HbO) and total-hemoglobin (HbT)
      in three regions of interest: the primary sensory-motor cortex (SM1), the
      premotor cortex (PMC), and the prefrontal cortex (PFC). The relative activation
      ratio of HbO and HbT was estimated for comparison of the relative activity of the
      left PMC or PFC to the left SM1. RESULTS: Mean values of HbO and HbT of the left
      SM1, PMC, and PFC were higher during movements of the right shoulder, compared
      with movements of the left hand. Relative activation ratios for movements of the
      right shoulder (HbO: PMC-104.5%, PFC-110.9%; HbT: PMC-136.3%, PFC-200.1%) were
      greater than 100%, and, by contrast, less than 100% (HbO: PMC-57.5%, PFC-84.8%;
      HbT: PMC-88.9%, PFC-70.3%) for movements of the right hand. CONCLUSIONS: Our
      results appear to indicate that movements of the shoulder require greater neural
      recruitment than movements of the hand. In addition, the PMC and PFC appeared to
      have greater involvement than the SM1 in movements of the shoulder; by contrast,
      the SM1 appears to have greater involvement than the PMC and PFC in movements of
      the hand.

PMID- 23867413
TI  - Outcomes of electrical stimulation of the neurogenic bladder: results of a two
      year follow-up study.
AB  - INTRODUCTION: The complications of neurogenic dysfunction of the urinary bladder
      still constitute an important cause of death among spinal cord injury patients.
      AIM OF STUDY: The aim of this study was to assess transcutaneous electrical
      stimulation of the urinary bladder as a treatment for micturition disorders in
      patients after spinal cord injury (SCI) over 2 years of follow-up. MATERIAL AND
      METHODS: The study involved 28 patients (22 men and 6 women) with neurogenic
      bladder dysfunction following a spinal cord injury. The patients were 16 to 68
      years old and 2 to 26 months since their spinal cord injury. The therapeutic
      programme involved 30 sessions of electrical stimulation of the urinary bladder,
      five sessions per week. The outcomes of electrical stimulation were assessed by
      comparing the results of urodynamic examinations performed before treatment,
      immediately on completion of the treatment and at 24 months post-treatment.
      RESULTS: Transcutaneous electrical stimulation of the urinary bladder produced a
      significant increase in bladder capacity (p = 0.001), which was higher by a mean
      of 117.7 ml immediately on completion of the treatment and a mean of 101.6 ml (p
      = 0.018) two years after the treatment. The amount of post-void residual urine in
      the bladder decreased by a mean of 81.9 ml (p = 0.007) immediately after
      completion of the treatment and a mean of 76.9 ml (p = 0.011) two years after the
      treatment. Opening pressure was lower by a mean of 3.1 cm H2O (p > 0.05)
      immediately on completion of the electrical stimulation treatment. Intravesical
      pressure at maximum flow decreased in 19 patients (68%) by a mean of 11.6 cm H2O
      (p > 0.05). At the late follow-up assessment, opening pressure was lower in 17
      patients (68%) by a mean of 6.7 cm H2O. Two patients demonstrated the micturition
      phase, which had been absent at baseline and immediately after completion of the
      treatment. Opening pressure in the entire group was lower compared to baseline by
      2.9 cm H2O (p > 0.05). Also in the late follow-up assessment, intravesical
      pressure at maximum flow was reduced in 21 patients (79%) by a mean of 9.6 cm H2O
      (p > 0.05). The maximum voiding velocity increased by a mean of 3.8 ml/s (p =
      0.008) immediately after treatment completion and by a mean of 3.6 ml/s (p <
      0.001) at two years post-treatment. CONCLUSIONS: Transcutaneous electrical
      stimulation of the neurogenic bladder in patients following spinal cord injury
      improves lower urinary tract function. Improved urinary tract function is seen
      two years following completion of the electrical stimulation treatment.

PMID- 23867414
TI  - What is post TBI fatigue?
AB  - BACKGROUND: Fatigue is among the most common sequelae of traumatic brain injury
      (TBI). OBJECTIVES: To summarize the empirical and theoretical literature on Post
      TBI fatigue (PTBIF) and identify some of the challenges that continue to confront
      clinicians, researchers and individuals with TBI. METHODS: Qualitative literature
      review. The epidemiology, characteristics, and correlates of PTBIF are described.
      Challenges in the operational definition and measurement of fatigue are discussed
      and the empirical literature on measurement of PTBIF and theoretical models of
      the potential etiology of PTBIF is summarized. Existing treatments of PTBIF and
      the research supporting them are reviewed. Future directions for clinical
      research are presented. RESULTS: Although PTBIF is a high incidence condition
      after TBI that is related to significant suffering and reduced quality of life,
      it remains inadequately measured and treated. Its etiology and precipitants are
      poorly understood and intervention research is inadequate. CONCLUSION: Further
      research is necessary to develop psychometrically-sound objective and subjective
      measures of PTBIF and examine the efficacy of treatments for fatigue.
      Interventions shown to improve fatigue in other populations should be considered
      in treating PTBIF.

PMID- 23867415
TI  - Individualised resting hand splints for adults with acquired brain injury: a
      randomized, single blinded, single case design.
AB  - AIM: To evaluate the effect of individualized resting mitt splints on
      hypertonicity (spasticity and tissue stiffness) and passive range of motion
      (PROM). METHODS: A randomized, single blinded, single case design. Ten adults
      with acquired brain injury were randomized to control (no-splint) and
      experimental (splint) groups. The experimental group received an individualized
      (wrist position, wearing schedule) thermoplastic resting mitt splint. Measures
      included wrist and finger PROM, muscle stiffness (Modified Ashworth Scale), and
      spasticity (Modified Tardieu Scale) which were taken at five time points.
      RESULTS: Between-group analyses indicated a statistically significant effect on
      PROM at the wrist (d = 2.14, CI95 = 0.57, 3.72, p < 0.05) and clinically
      important effects on finger PROM, and wrist and finger spasticity and stiffness.
      Within-group analyses indicated that splint-wear resulted in positive clinical
      effects ranging from zero effect (maintenance of pre-splinting status) to a large
      positive treatment effect. Non splint-wear resulted in negative clinical effects
      ranging from zero effect to a large negative treatment effect. CONCLUSION:
      Individualized resting splints for adults with moderate hypertonicity and no soft
      tissue contracture resulted in positive clinical effects to PROM, muscle
      stiffness and spasticity. Long-term splint-wear may be more beneficial than short
      term wear, and may prevent the negative changes evident with no splint-wear.
      Resting hand splints should be considered for a select group where reduction in
      muscle stiffness and spasticity, or maintenance of PROM, is desired.

PMID- 23867416
TI  - Generalization of word retrieval following semantic feature treatment.
AB  - OBJECTIVES: The effectiveness of a Semantic Feature Treatment (SFT) at increasing
      word retrieval accuracy of untreated words was examined in relation to the
      influence of the number of shared features with treated words. Generalization of
      these improvements to discourse was also examined. METHODS: Three adults with
      chronic aphasia completed 12 SFT sessions. Generalization to untreated words with
      many shared features (SFs) and with no shared features (NSFs), as well as
      generalization to discourse tasks, was analyzed. RESULTS: All participants
      improved in word retrieval accuracy for treated words. Accuracy of retrieving
      untreated words improved for two participants. Retrieval accuracy for untreated
      words with SF improved more than for words with NSF. Generalization of
      improvements to discourse tasks occurred for two participants. CONCLUSIONS: SFT
      improves word retrieval accuracy for some people with aphasia during
      confrontation naming and discourse tasks. Generalization may be slightly higher
      for untreated words with SFs than untreated words with NSFs. Future research is
      needed to further investigate the effect shared features have on generalization
      of improvements, and to determine candidacy for SFT.

PMID- 23867417
TI  - Long term language recovery subsequent to low frequency rTMS in chronic non
      fluent aphasia.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a
      potential therapeutic tool for the rehabilitation of language in chronic non
      fluent aphasia post-stroke. Previous studies report that low frequency (1 Hz)
      rTMS applied to homologous language sites can facilitate behavioural language
      changes. Improvements in picture naming performance and speech output are
      frequently reported. OBJECTIVES: This study aims to assess the efficacy of
      inhibitory rTMS to modulate language performance in non-fluent aphasia. METHODS:
      Low-frequency (1 Hz) rTMS was applied to six active stimulation and six placebo
      patients for 20 min per day over 10 days, as outlined in a previous published
      investigation. Behavioural language outcome measures were taken at baseline (pre
      stimulation) and 1 week, 2 months, 8 months and 12 months post-stimulation.
      RESULTS: The findings demonstrate treatment-related changes observed in the
      stimulation group, up to 12 months post-stimulation, when compared to the placebo
      control group over time for naming performance, expressive language and auditory
      comprehension. CONCLUSION: These outcomes provide considerable evidence to
      support the theory of rTMS modulating mechanisms of transcallosal disinhibition
      in the aphasic brain, and highlight the potential clinical application of rTMS
      for language rehabilitation in chronic aphasia.

PMID- 23867418
TI  - 'Stroke a Chord': the effect of singing in a community choir on mood and social
      engagement for people living with aphasia following a stroke.
AB  - BACKGROUND: Communication deficits resulting from aphasia can negatively impact
      stroke survivors' relationships and social participation. Despite their
      difficulties, singing is accessible and enjoyable for many people with aphasia.
      OBJECTIVES: To explore the effects of group singing for people with aphasia.
      METHODS: A community choir was established and facilitated by a neurologic music
      therapist. Mood (General Health Questionnaire-12; Visual Analogue Mood Scale),
      communication, cognition and global functioning (Stroke Impact Scale-3) and
      social functioning (Sense of Belonging Instrument) were measured before, and at
      12-weeks and 20-weeks after joining the choir. Three choir members and five
      caregivers also completed semi-structured interviews about their experience of
      the choir. RESULTS: Baselines measures were collected for 13 participants with
      aphasia. Prior to joining the choir, participants had higher levels of negative
      mood symptoms and poorer subjective sense of belonging compared to Australian
      general population samples. Results from the GHQ-12 suggested a trend towards
      reduction of psychological distress after participating in the choir. Thematic
      analysis of the interviews revealed five common themes: increased confidence,
      peer support, enhanced mood, increased motivation, and changes to communication.
      CONCLUSION: The strength of findings was limited by the number of participants
      and lack of a control group, however clear benefits of choir participation were
      demonstrated. Preliminary findings were encouraging and warrant further rigorous
      investigation.

PMID- 23867419
TI  - Effects of a new sensory re-education training tool on hand sensibility and
      manual dexterity in people with multiple sclerosis.
AB  - OBJECTIVE: To describe and evaluate the effects of a new home-based sensory re
      education training tool on hand sensibility and manual dexterity in people with
      MS experiencing upper limb sensory deficits. METHODS: Twenty-five people with
      relapsing-remitting MS (18 women), mean age 50.6 years (SD = 11.4), volunteered
      to participate. Participants were initially assigned to a 7-week control phase
      followed by a 3-week home-based sensory re-education phase. Measurements used
      were the nine-hole peg test, the two point discrimination test, the monofilaments
      test and the functional dexterity test. Measurements were collected at baseline,
      following the control phase and at the end of the trial. RESULTS: Participants
      demonstrated an improvement in the nine-hole peg (26.8 (SD = 3.5) vs. 22.6 (SD =
      3.2); mean difference (95% CI) 4.9 (0.9, 7.1), P = 0.03) and functional dexterity
      tests (38.6 (SD = 4.4) vs. 33.8 (SD = 4.9); mean difference (95% CI) 4.8 (1.8,
      7.0); P = 0.02) at the end of the sensory re-education phase compared to the end
      of the control phase. No differences were observed as to the monofilaments and
      two-point discrimination tests. CONCLUSIONS: Sensory re-education training does
      not affect the level of sensory impairment in the hand but may lead to
      improvement in select measures of manual dexterity.

PMID- 23867420
TI  - Do swallowing exercises improve swallowing dynamic and quality of life in
      Parkinson's disease?
AB  - OBJECTIVE: To investigate the effect of motor swallowing exercises on swallowing
      dynamic, quality of life and swallowing complaints in Parkinson's disease (PD).
      DESIGN: A before-after trial. SETTING: University Medical Center. PARTICIPANTS:
      Parkinson's disease patients with dysphagia complaints. INTERVENTIONS: Motor
      swallowing exercises designed to increase the strength and range of motion of the
      mouth, larynx and pharyngeal structures, coordination between breathing and
      swallowing, and airway protection. Patients should perform the exercises twice a
      day, five days a week, for five weeks. MAIN OUTCOME MEASURE(S): The primary
      outcome was the difference before and after the intervention in number of
      swallowing videofluoroscopic events (Swallowing Score). The secondary outcomes
      were quality of life (QOL) and swallowing complaints. RESULTS: Fifteen patients
      concluded the study (10 man/5 woman; mean age 59.2 +/- 9.17). The
      videofluoroscopic events with greater improvement were loss of bolus control (P <
      0.03), piecemeal swallow (P = 0.05) and residue on the tongue (P < 0.01),
      valleculae (P = 0.01) and pyriform sinuses (P = 0.05). Lingual pumping and dental
      absence were interfering factors associated with treatment failure (beta
      standardized coefficient = -16.6, 26.2; P = 0.02, 0.002, respectively). The
      domains with greater improvements in QOL were fear (P = 0.02) and symptom
      frequency (P = 0.05). Regarding swallowing complaints, patients reported to have
      reduced mainly their difficulty in moving food in the mouth when chewing (P =
      0.02). Reduction in swallowing disorders was not related with QOL improvement
      (cor = 0.13, [95% CI, 0.6-0.4], P = 0.63). CONCLUSIONS: Motor swallowing
      exercises may reduce swallowing disorders in PD patients without lingual pumping
      and dental absence and impact positively QOL and swallowing complaints in
      individuals with PD.

PMID- 23867421
TI  - Measuring mobility in patients living in the community with Parkinson disease.
AB  - QUESTION: Is the de Morton Mobility Index (DEMMI) valid for measuring the
      mobility of patients living in the community with Parkinson disease (PD)? DESIGN:
      A prospective cohort study comparing the DEMMI with existing mobility-related
      activity measures. PARTICIPANTS: 102 consecutive patients with PD (mean age 72.4
      years, SD 8.3) who received multidisciplinary outpatient care in a community
      rehabilitation facility over 6 to 8 weeks. OUTCOME MEASURES AND ANALYSIS: The
      DEMMI and other measures of mobility-related activity at admission and discharge
      (10 metre walk test, Berg balance scale, timed up and go test, functional reach
      test and pull test) were used to assess convergent validity. Discriminant
      validity of the DEMMI was assessed by comparison to measures of other constructs,
      and. unidimensionality was examined using Rasch analysis. RESULTS: Evidence of
      convergent (rho ranged from 0.47 to 0.84), discriminant (rho ranged 0.12 to
      0.22), and known groups validity were obtained for the DEMMI (Mean difference
      20.3 units, 95% CI 14.5 to 26.0). Rasch analysis confirmed that the DEMMI was
      unidimensional. CONCLUSION: The DEMMI has a broader scale width than existing
      mobility-related activity measures, provides interval level measurement and is a
      unidimensional measure of mobility in patients with PD living in the community.

PMID- 23867423
TI  - The clinical use of cetirizine in the treatment of allergic rhinitis.
AB  - BACKGROUND: Cetirizine is among the first second-generation H1 antihistamines
      (SGAHs) developed to provide selective H1 receptor inhibition without central
      nervous system depression. OBJECTIVE: The aim of this review is to summarize the
      amount of data collected over 25 years of clinical use of cetirizine and compare
      this with data available for other SGAHs in the management of patients with
      allergic rhinitis (AR). METHODS: A comprehensive literature search for
      publications relating to cetirizine was performed using the Pubmed database, and
      relevant papers published in English were selected for detailed review. RESULTS:
      Compared with the majority of other SGAHs, cetirizine was generally shown to have
      a more favourable pharmacological profile, to be well tolerated, be at least
      equally or more efficacious in attenuating/inhibiting nasal and ocular symptoms
      and to improve the quality of life in AR patients. The majority of clinical
      trials investigating the effect of SGAHs in AR patients further indicated that
      cetirizine was often employed as the main comparator active drug. CONCLUSION:
      Based on the evidence that cetirizine is a commonly employed active comparator
      drug in AR, it is tempting to suggest that cetirizine may be a suitable benchmark
      in the development of novel pharmacotherapies for AR.

PMID- 23867422
TI  - Training effects of a 12-week walking program on Parkinson disease patients and
      community-dwelling older adults.
AB  - BACKGROUND: Introducing evidence-based exercise guidelines of Parkinson's disease
      (PD) into clinical practice and community settings has been highlighted. AIM:
      This study tested the feasibility and compared the weekly effects of a 12-week
      walking training program on PD patients and community-dwelling seniors. DESIGN: A
      prospective quasi-experimental design was used. PD patients in Hoehn and Yahr
      Stage I through III (PG) and community-dwelling adults older than 65 were
      recruited (CG). METHODS: In the outpatient department of a hospital, the
      information of personal data, coordination test, and walking ability of
      participants were collected first. They then participated in a 36-session, 12
      week treadmill walking training program. RESULTS: Weekly data of step length and
      velocity in PG and CG were collected. The walking training program achieved
      significant velocity (chi2 = 126.38, p < 0.001) and step length (chi2 = 27.27, p
      = 0.001) improvements in PG. Differences in improvement between PG and CG in
      terms of velocity (chi2 = 7.089, df = 1, p = 0.008) and step length (chi2 =
      7.718, df = 1, p = 0.005) were also identified. CONCLUSION: The applicability of
      this 12-week walking program both for PD patients and community-dwelling older
      adults was identified. Conducting the economic evaluation and neurology studies
      of the 12-week walking program and test the effects of five-week walking program
      are suggested.

PMID- 23867424
TI  - Women with coronary artery disease: do psychosocial factors contribute to a
      higher cardiovascular risk?
AB  - Despite the mortality and morbidity burden associated with cardiovascular disease
      in women, there is insufficient knowledge regarding gender specificities in both
      biomedical and psychosocial domains. Gender differences in both pathophysiology
      and biological risk factors might explain distinct prevalence rates, symptom
      profiles, and even medical outcomes, but gender-related specificities regarding
      psychosocial risk factors might further explain this. The authors review the key
      issues on this topic and outline suggestions for future research. Ultimately, a
      better understanding of this matter will translate not only into improved
      clinical management of female patients, but also gender-specific strategies in
      the prevention of cardiovascular disease. 

PMID- 23867425
TI  - Temporal evolution and implications of ventricular arrhythmias associated with
      acute myocardial infarction.
AB  - It is important that clinicians have a clear understanding of the significance of
      ventricular arrhythmias (VAs) that occur in the context of acute myocardial
      infarction depending on the type of VA and timing in relation to the myocardial
      injury. This will greatly assist in evaluating prognostic implications and
      tailoring optimal strategies for management. This review presents an update on
      the current understanding of the pathogenesis, incidence, and clinical features
      of postinfarction VAs, and outcomes and potential therapeutic options. 

PMID- 23867426
TI  - A new roadmap for mechanical circulatory support in children.

PMID- 23867428
TI  - A systematic review and meta-analysis on the effect of steroids in pediatric
      shock.
AB  - OBJECTIVE: To systematically review randomized controlled trials (RCTs) of
      steroids conducted in children with fluid and/or vasoactive medication-dependent
      shock and evaluate and report on the quality and clinical and methodological
      heterogeneity of included trials. DATA SOURCES: MEDLINE (1946 to January Week 2,
      2012), Embase (1947-January 20, 2012), Cochrane Central Register of Controlled
      Trials (through January 2012), and reference lists of retrieved publications. No
      language restrictions were applied. STUDY SELECTION: We included only RCTs
      reporting on steroid use and clinical outcomes in pediatric shock. DATA
      EXTRACTION: Study characteristics, interventions, and outcomes were retrieved by
      three independent reviewers. Pooled relative risks and 95% CIs were calculated
      using a random effects model. DATA SYNTHESIS: We identified 535 citations from
      which 13 full-text articles were retrieved for assessment. Eight articles
      evaluating a total of 447 children were selected for review. The median trial
      size was 67 patients (range, 28-98). Seven of the eight trials were published
      prior to 1996, and all trials were conducted in the developing world, and six of
      eight trials were in the setting of dengue shock. We found methodological issues
      related to allocation concealment, blinding and reporting of co-interventions,
      and outcome data among the included trials along with varying types, doses,
      timings, and duration of steroids making it difficult to compare outcomes. The
      overall meta-analysis showed no difference in mortality rates between those who
      did and did not receive steroids (relative risks, 0.744 [95% CI, 0.475-1.165]; p
      = 0.197). CONCLUSIONS: The literature on the use of steroids in pediatric shock
      is limited in amount and methodological quality and demonstrates conflicting
      results. The limited evidence on which current guidelines are based strongly
      supports the need for a well-designed, pragmatic randomized controlled trial on
      the use of steroids in pediatric shock to inform future guidelines.

PMID- 23867427
TI  - Are pediatric critical care medicine fellowships teaching and evaluating
      communication and professionalism?
AB  - OBJECTIVES: To describe the teaching and evaluation modalities used by pediatric
      critical care medicine training programs in the areas of professionalism and
      communication. DESIGN: Cross-sectional national survey. SETTING: Pediatric
      critical care medicine fellowship programs. SUBJECTS: Pediatric critical care
      medicine program directors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Survey response rate was 67% of program directors in the United States,
      representing educators for 73% of current pediatric critical care medicine
      fellows. Respondents had a median of 4 years experience, with a median of seven
      fellows and 12 teaching faculty in their program. Faculty role modeling or direct
      observation with feedback were the most common modalities used to teach
      communication. However, six of the eight (75%) required elements of communication
      evaluated were not specifically taught by all programs. Faculty role modeling was
      the most commonly used technique to teach professionalism in 44% of the content
      areas evaluated, and didactics was the technique used in 44% of other
      professionalism content areas. Thirteen of the 16 required elements of
      professionalism (81%) were not taught by all programs. Evaluations by members of
      the healthcare team were used for assessment for both competencies. The use of a
      specific teaching technique was not related to program size, program director
      experience, or training in medical education. CONCLUSIONS: A wide range of
      techniques are currently used within pediatric critical care medicine to teach
      communication and professionalism, but there are a number of required elements
      that are not specifically taught by fellowship programs. These areas of
      deficiency represent opportunities for future investigation and improved
      education in the important competencies of communication and professionalism.

PMID- 23867429
TI  - Quality metrics in neonatal and pediatric critical care transport: a consensus
      statement.
AB  - OBJECTIVES: The transport of neonatal and pediatric patients to tertiary care
      medical centers for specialized care demands monitoring the quality of care
      delivered during transport and its impact on patient outcomes. Accurate
      assessment of quality indicators and patient outcomes requires the use of a
      standard language permitting comparisons among transport programs. No consensus
      exists on a set of quality metrics for benchmarking transport teams. The aim of
      this project was to achieve consensus on appropriate neonatal and pediatric
      transport quality metrics. DESIGN: Candidate quality metrics were identified
      through literature review and those metrics currently tracked by each program.
      Consensus was governed by nominal group technique. Metrics were categorized in
      two dimensions: Institute of Medicine quality domains and Donabedian's
      structure/process/outcome framework. SETTING: Two-day Ohio statewide quality
      metrics conference. SUBJECTS: Nineteen transport leaders and staff representing
      six statewide neonatal/pediatric specialty programs convened to achieve
      consensus. MEASUREMENT AND MAIN RESULTS: Two hundred fifty-seven performance
      metrics relevant to neonatal/pediatric transport were identified. Eliminating
      duplicate and overlapping metrics resulted in 70 candidate metrics. Nominal group
      methodology yielded 23 final quality metrics, the largest portion representing
      Donabedian's outcome category (n = 12, 52%) and the Institute of Medicine quality
      domains of effectiveness (n = 7, 30%) and safety (n = 9, 39%). Sample final
      metrics include measurement of family presence, pain management, intubation
      success, neonatal temperature control, use of lights and sirens, and medication
      errors. Lastly, a definition for each metric was established and agreed upon for
      consistency among institutions. CONCLUSIONS: This project demonstrates that
      quality metrics can be achieved through consensus building and provides the
      foundation for benchmarking among neonatal and pediatric transport programs and
      quality improvement projects.

PMID- 23867430
TI  - The impact of a quality improvement intervention to reduce nosocomial infections
      in a PICU.
AB  - OBJECTIVE: To evaluate whether a quality improvement intervention could reduce
      nosocomial infection rates in a PICU and improve patient outcomes. DESIGN:
      Prospective interventional cohort study conducted during three periods:
      preintervention period, intervention period, and long-term follow-up. SETTING: A
      14-bed medical and surgical PICU in a university hospital for children.
      INTERVENTIONS: The quality improvement intervention consisted of the creation of
      an infection control team, a program targeting hand hygiene, and quality
      practices focused on preventing nosocomial infections. MEASUREMENTS AND MAIN
      RESULTS: We included 851 patients in the preintervention period, 822 in the
      intervention period, and 940 in the long-term follow-up period. Compared with the
      preintervention period, in the intervention period, the rates of central line
      associated bloodstream infection decreased from 8.1 to 6/1,000 central venous
      catheter-days (p = 0.640), ventilator-associated pneumonia decreased from 28.3 to
      10.6/1,000 days' ventilation (p = 0.005), and catheter-associated urinary tract
      infection decreased from 23.3 to 5.8/1,000 urinary catheter-days (p < 0.001).
      Furthermore, hospital length of stay decreased from 18.56 to 14.57 days (p =
      0.035) and mortality decreased from 5.1% to 3.3% (p = 0.056). Multivariable
      logistic regression found that nosocomial infections was independently associated
      with increased mortality (odds ratio, 2.35 [95% CI, 1.02-5.55]; p = 0.046).
      Compared with the preintervention period, in the long-term follow-up period,
      central line-associated bloodstream infection decreased to 4.6/1,000 central
      venous catheter-days (p = 0.205); ventilator-associated pneumonia decreased to
      9.1/1,000 ventilation-days (p = 0.001), and catheter-associated urinary tract
      infection decreased to 5.2/1,000 urinary catheter-days (p < 0.001). Hospital
      length of stay (14.45 days; p = 0.048) and mortality (3.2%; p = 0.058) also
      decreased. CONCLUSIONS: A multifaceted quality improvement intervention reduced
      nosocomial infection rates, hospital length of stay, and mortality in our PICU.
      The effects of the intervention were sustained over time.

PMID- 23867431
TI  - Communication and professionalism: are we caught napping?

PMID- 23867432
TI  - Expanding the conversation regarding adjunctive corticosteroid therapy for
      pediatric septic shock.

PMID- 23867433
TI  - Asthma, steroids, and surveys...science or merely my opinion?

PMID- 23867434
TI  - Learning curve for arterial cannulation using ultrasound: a myth or reality?

PMID- 23867435
TI  - Minimize stress and maximize clinical outcome!

PMID- 23867436
TI  - Big data in pediatric cardiac care: is it time?.

PMID- 23867437
TI  - Brain natriuretic Peptide predicting outcome after congenital heart surgery ...
      are we there yet?

PMID- 23867438
TI  - The power of "we": successful quality improvement requires a team approach.

PMID- 23867439
TI  - Pediatric ventilator-associated tracheobronchitis and pneumonia: time to regroup?

PMID- 23867440
TI  - Impaired mobilization of endothelial progenitor cells in acute lung injury/acute
      respiratory distress syndrome: inhibition of an endogenous mechanism of lung
      repair.

PMID- 23867441
TI  - Paralytics use should be cautioned in the prediction for prognosis after hypoxic
      injury.

PMID- 23867442
TI  - Observational studies of glucose homeostasis are susceptible to sampling
      frequency bias.

PMID- 23867443
TI  - The authors reply.

PMID- 23867444
TI  - Mobilization of endothelial progenitor cells from bone marrow is impaired in a
      piglet model of acute respiratory distress syndrome.
AB  - OBJECTIVES: To characterize the endothelial progenitor cell mobilization in the
      models of moderate and severe lung injury, we hypothesized that there were
      differences in endothelial progenitor cell levels and mobilizing cytokines
      between moderate and severe lung injury. DESIGN: Prospective, randomized, and
      controlled experimental study. SETTING: University research laboratory center.
      SUBJECTS: Fifteen healthy piglets. INTERVENTIONS: Piglets were randomly allocated
      to control, moderate lung injury (acute lung injury), and severe lung injury
      (acute respiratory distress syndrome) groups. Lung injury was established by
      intravenous infusion of oleic acid. Animals were mechanically ventilated for 24
      48 hours, and then animals were weaned from ventilation and cared for until day
      7. MEASUREMENTS AND MAIN RESULTS: Endothelial progenitor cells were quantified by
      flow cytometry. After 24 hours, the number of endothelial progenitor cells in
      peripheral blood increased in the acute lung injury group but was not altered in
      the acute respiratory distress syndrome group compared to the control group. The
      number of CD34KDR, KDRCD133, and CD34KDRCD133 cells was higher in the acute lung
      injury group than in the acute respiratory distress syndrome group. In bone
      marrow, the number of CD34KDR and KDRCD133 cells was greater in acute respiratory
      distress syndrome animals but not altered in acute lung injury animals at 24
      hours. Furthermore, plasma stromal cell-derived factor-1 and vascular endothelial
      growth factor concentrations were higher in acute lung injury than in acute
      respiratory distress syndrome at 24 hours. Matrix metalloproteinase-9 and soluble
      kit ligand levels in bone marrow were reduced in acute respiratory distress
      syndrome compared with acute lung injury. Lung CD34, KDR, and lung stromal cell
      derived factor-1 messenger RNA expression were higher in the acute lung injury
      group than in the acute respiratory distress syndrome group. Furthermore, the
      expression of CD34, KDR, and CD133 messenger RNA in lung tissue was correlated
      with stromal cell-derived factor-1 in the lung. CONCLUSIONS: There was a rapid
      release of endothelial progenitor cells from bone marrow into circulation in
      moderate acute lung injury, and endothelial progenitor cell mobilization was
      impaired in acute respiratory distress syndrome.

PMID- 23867445
TI  - Cardiac dysfunction in pneumovirus-induced lung injury in mice.
AB  - OBJECTIVE: To determine biventricular cardiac function in pneumovirus-induced
      acute lung injury in spontaneously breathing mice. DESIGN: Experimental animal
      study. SETTING: Animal laboratory. SUBJECTS: C57Bl/6 mice. INTERVENTION: Mice
      were inoculated with the rodent pneumovirus, pneumonia virus of mice.
      MEASUREMENTS AND MAIN RESULTS: Pneumonia virus of mice-infected mice were studied
      for right and left ventricular function variables by high-field strength (7
      Tesla) cardiac MRI at specific time points during the course of disease compared
      with baseline. One day before and at peak disease severity, pneumonia virus of
      mice-infected mice showed significant right and left ventricular systolic and
      diastolic volume changes, with a progressive decrease in stroke volume and
      ejection fraction. No evidence for viral myocarditis or viral presence in heart
      tissue was found. CONCLUSIONS: These findings show adverse pulmonary-cardiac
      interaction in pneumovirus-induced acute lung injury, unrelated to direct virus
      mediated effects on the heart.

PMID- 23867446
TI  - A systematic review of surgeon-patient communication: strengths and opportunities
      for improvement.
AB  - OBJECTIVE: Effective communication is critical to patient satisfaction, outcomes
      of care and malpractice prevention. Surgeons need particularly effective
      communication skills to discuss complicated procedures and help patients make
      informed choices. We conducted a systematic review of the literature on surgeon
      patient communication. METHODS: Searches were conducted in MEDLINE, PsycINFO, and
      Sociological Abstract. Two reviewers screened citations and full-text articles.
      Quality was appraised using the Critical Appraisal Skills Program tool. Studies
      were categorized into content of communication, patient satisfaction,
      relationship of communication to malpractice, and duration of visits. RESULTS:
      2794 citations and 74 full-text articles, 21 studies and 13 companion reports
      were included. Surgeons spent the majority of their time educating patients and
      helping them to make choices. Surgeons were generally thorough in providing
      details about surgical conditions and treatments. Surgeons often did not explore
      the emotions or concerns of patients. Potential areas of improvement included
      discussing some elements of informed decision making, and expressing empathy.
      CONCLUSION: Surgeons can enhance their communication skills, particularly in
      areas of relative deficiency. Studies in primary care demonstrate communication
      programs are effective in teaching these skills. PRACTICE IMPLICATIONS: These can
      be adapted to surgical training and ultimately lead to improved outcomes and
      satisfaction with care.

PMID- 23867447
TI  - Necdin, a p53 target gene, in stem cells.

PMID- 23867448
TI  - Association between reversal of multidrug resistance by methyl jasmonate and P
      glycoprotein ATPase activity in hepatocellular carcinoma.
AB  - OBJECTIVE: To study the effects of methyl jasmonate on multidrug resistance in a
      mouse model of hepatocellular carcinoma. METHODS: Multidrug resistant H22
      (H22/FAP) hepatocellular carcinoma cells were produced in vitro by continuous
      exposure to increasing doses of doxorubicin, cisplatin and 5-fluorouracil (FAP
      regimen). Cell toxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolum bromide (MTT) assay. Survival time was calculated for BALB/c
      mice that received intraperitoneal injections of H22/FAP cells followed by
      treatment with methyl jasmonate or verapamil in combination with FAP for 7 days.
      Adenosine triphosphate (ATP) hydrolysis was used to measure the activity of
      permeability-glycoprotein (P-gp) ATPase activity in plasma membranes. RESULTS:
      The MTT assay showed that methyl jasmonate significantly enhanced the
      cytotoxicity of the FAP regimen in multidrug resistant H22/FAP cells. Methyl
      jasmonate (10 mg/kg and 5 mg/kg) combined with FAP significantly increased
      survival time in BALB/c mice by 44.25% and 48.01%, respectively, compared with
      FAP. Methyl jasmonate increased P-gp ATPase activity. CONCLUSION: The combined
      use of methyl jasmonate and the FAP regimen might be a novel strategy for
      overcoming the multidrug resistance often observed in hepatocellular carcinoma.

PMID- 23867449
TI  - Increased expression of sex determining region Y-box 11 (SOX11) in cutaneous
      malignant melanoma.
AB  - OBJECTIVES: To observe sex determining region Y-box 11 (SOX11) gene expression in
      cutaneous malignant melanoma and its effect on tumour cell proliferation.
      METHODS: Clinicopathological data and tissue samples from patients with cutaneous
      malignant melanoma, together with tissue samples from healthy volunteers
      (controls), were retrospectively reviewed. Protein levels of SOX11 and the
      antigen identified by monoclonal antibody Ki-67 (Ki-67) in skin lesions were
      analysed using immunohistochemistry. The correlation between protein levels and
      clinipathological parameters was investigated. RESULTS: Out of 40 patient
      samples, 25 (62.5%) were positive for SOX11 protein in malignant melanoma tissue.
      This was significantly higher than in 40 control tissue samples, in which no
      SOX11 protein was detected. Presence of SOX11 protein was positively related to
      the proliferation index of cutaneous malignant melanoma tumour cells. Presence of
      SOX11 protein in cutaneous malignant melanoma was related to tumour type, tumour
      location, lymph node metastasis and 5-year survival rate. CONCLUSION: Human
      cutaneous malignant melanoma tissues expressed high levels of SOX11 compared with
      healthy controls, suggesting that SOX11 may be a new prognostic marker for
      malignant melanoma.

PMID- 23867450
TI  - Diagnostic accuracy of neutrophil CD64 expression in neonatal infection: a meta
      analysis.
AB  - OBJECTIVE: The aim of the present study was to establish the predictive values of
      neutrophil CD64 expression in diagnosing neonatal infection. METHODS: A
      comprehensive search of the PubMed and Embase(r) literature databases identified
      outcome data from published studies estimating the diagnostic accuracy of
      neutrophil CD64 expression for neonatal infection. Summary estimates for
      sensitivity, specificity, diagnostic odds ratios (DOR) and the area under the
      summary receiver operating characteristic curve (AUC) were calculated using a
      bivariate random-effects approach. RESULTS: Twelve studies including 1915
      neonates were analysed. Summary estimates (95% confidence intervals) for CD64
      expression in the diagnosis of neonatal infection were: sensitivity, 0.78 (0.75,
      0.81); specificity, 0.81 (0.78, 0.83); DOR, 21.27 (11.71, 38.65); positive
      likelihood ratio, 4.53 (3.22, 6.36); negative-likelihood ratio, 0.23 (0.14,
      0.37); AUC, 0.89. CONCLUSIONS: Neutrophil CD64 expression can be used as an
      additional test in the diagnosis of neonatal infection. Results of a CD64 assay
      should not be used alone to diagnose such infections, but should be interpreted
      in combination with other test results and clinical findings.

PMID- 23867451
TI  - J wave is associated with increased risk of sudden cardiac arrest in patients
      with hypertrophic cardiomyopathy.
AB  - AIMS: A retrospective, case-control study to investigate the J wave, a J-point
      elevation on resting 12-lead electrocardiograms, as a risk factor for sudden
      cardiac arrest (SCA) in patients diagnosed with hypertrophic cardiomyopathy
      (HCM). METHODS: Patients with HCM and age- and sex-matched healthy control
      subjects were recruited, and 12-lead electrocardiograms were performed. The
      prevalence and related characteristics of J waves were assessed. Patients were
      followed-up for a mean of 47.9 months. RESULTS: Patients with HCM (n = 345) had
      significantly higher prevalence of J waves than healthy controls (n = 690; 11.6%
      and 7.1%, respectively). During follow-up, 14 patients with HCM experienced SCA
      (SCA subgroup). The prevalence of J waves was significantly higher in the SCA
      subgroup than in the non-SCA subgroup (42.9% and 10.3%, respectively). There were
      no significant differences between the SCA and non-SCA subgroups in J wave
      morphology. CONCLUSION: The J wave may be a risk factor for SCA in patients with
      HCM.

PMID- 23867452
TI  - The role of the ERK1/2 signalling pathway in the pathogenesis of female stress
      urinary incontinence.
AB  - OBJECTIVE: To investigate the role of extracellular-regulated protein kinase
      (ERK)1/2 and phosphorylated (p)-ERK1/2 in the pathogenesis of female stress
      urinary incontinence (SUI). METHODS: Anterior vaginal wall tissue was collected
      from women with SUI and control subjects. Immunohistochemistry and Western
      blotting were performed for p-ERK1/2. Primary vaginal fibroblast cultures were
      incubated in the presence or absence of PD98059 (an inhibitor of ERK kinase) and
      levels of collagen I and III mRNA and protein were examined by quantitative
      reverse transcription-polymerase chain reaction and Western blot, respectively.
      RESULTS: Levels of p-ERK1/2 were significantly lower in vaginal wall tissue from
      patients with SUI (n = 10) compared with controls (n = 10). PD98059 treatment
      significantly reduced levels of collagen I and III mRNA and protein. CONCLUSIONS:
      Female SUI is associated with reduced levels of p-ERK1/2 compared with controls,
      and inhibition of the ERK1/2 signalling pathway inhibits collagen type I and III
      synthesis in vaginal wall fibroblasts.

PMID- 23867453
TI  - Lipid II-independent trans editing of mischarged tRNAs by the penicillin
      resistance factor MurM.
AB  - Streptococcus pneumoniae is a causative agent of nosocomial infections such as
      pneumonia, meningitis, and septicemia. Penicillin resistance in S. pneumoniae
      depends in part upon MurM, an aminoacyl-tRNA ligase that attaches L-serine or L
      alanine to the stem peptide lysine of Lipid II in cell wall peptidoglycan. To
      investigate the exact substrates the translation machinery provides MurM, quality
      control by alanyl-tRNA synthetase (AlaRS) was investigated. AlaRS mischarged
      serine and glycine to tRNA(Ala), as observed in other bacteria, and also
      transferred alanine, serine, and glycine to tRNA(Phe). S. pneumoniae tRNA(Phe)
      has an unusual U4:C69 mismatch in its acceptor stem that prevents editing by
      phenylalanyl-tRNA synthetase (PheRS), leading to the accumulation of
      misaminoacylated tRNAs that could serve as substrates for translation or for
      MurM. Although the peptidoglycan layer of S. pneumoniae tolerates a combination
      of both branched and linear muropeptides, deletion of MurM results in a reversion
      to penicillin sensitivity in strains that were previously resistant. However,
      because MurM is not required for cell viability, the reason for its functional
      conservation across all strains of S. pneumoniae has remained elusive. We now
      show that MurM can directly function in translation quality control by acting as
      a broad specificity lipid-independent trans editing factor that deacylates tRNA.
      This activity of MurM does not require the presence of its second substrate,
      Lipid II, and can functionally substitute for the activity of widely conserved
      editing domain homologues of AlaRS, termed AlaXPs proteins, which are themselves
      absent from S. pneumoniae.

PMID- 23867454
TI  - The catalytic domain of topological knot tRNA methyltransferase (TrmH)
      discriminates between substrate tRNA and nonsubstrate tRNA via an induced-fit
      process.
AB  - A conserved guanosine at position 18 (G18) in the D-loop of tRNAs is often
      modified to 2'-O-methylguanosine (Gm). Formation of Gm18 in eubacterial tRNA is
      catalyzed by tRNA (Gm18) methyltransferase (TrmH). TrmH enzymes can be divided
      into two types based on their substrate tRNA specificity. Type I TrmH, including
      Thermus thermophilus TrmH, can modify all tRNA species, whereas type II TrmH, for
      example Escherichia coli TrmH, modifies only a subset of tRNA species. Our
      previous crystal study showed that T. thermophilus TrmH is a class IV S-adenosyl
      l-methionine-dependent methyltransferase, which maintains a topological knot
      structure in the catalytic domain. Because TrmH enzymes have short stretches at
      the N and C termini instead of a clear RNA binding domain, these stretches are
      believed to be involved in tRNA recognition. In this study, we demonstrate by
      site-directed mutagenesis that both N- and C-terminal regions function in tRNA
      binding. However, in vitro and in vivo chimera protein studies, in which four
      chimeric proteins of type I and II TrmHs were used, demonstrated that the
      catalytic domain discriminates substrate tRNAs from nonsubstrate tRNAs. Thus, the
      N- and C-terminal regions do not function in the substrate tRNA discrimination
      process. Pre-steady state analysis of complex formation between mutant TrmH
      proteins and tRNA by stopped-flow fluorescence measurement revealed that the C
      terminal region works in the initial binding process, in which nonsubstrate tRNA
      is not excluded, and that structural movement of the motif 2 region of the
      catalytic domain in an induced-fit process is involved in substrate tRNA
      discrimination. 

PMID- 23867455
TI  - Aminoacylating urzymes challenge the RNA world hypothesis.
AB  - We describe experimental evidence that ancestral peptide catalysts substantially
      accelerated development of genetic coding. Structurally invariant 120-130-residue
      Urzymes (Ur = primitive plus enzyme) derived from Class I and Class II aminoacyl
      tRNA synthetases (aaRSs) acylate tRNA far faster than the uncatalyzed rate of
      nonribosomal peptide bond formation from activated amino acids. These new data
      allow us to demonstrate statistically indistinguishable catalytic profiles for
      Class I and II aaRSs in both amino acid activation and tRNA acylation, over a
      time period extending to well before the assembly of full-length enzymes and even
      further before the Last Universal Common Ancestor. Both Urzymes also exhibit ~60%
      of the contemporary catalytic proficiencies. Moreover, they are linked by
      ancestral sense/antisense genetic coding, and their evident modularities suggest
      descent from even simpler ancestral pairs also coded by opposite strands of the
      same gene. Thus, aaRS Urzymes substantially pre-date modern aaRS but are,
      nevertheless, highly evolved. Their unexpectedly advanced catalytic repertoires,
      sense/antisense coding, and ancestral modularities imply considerable prior
      protein-tRNA co-evolution. Further, unlike ribozymes that motivated the RNA World
      hypothesis, Class I and II Urzyme.tRNA pairs represent consensus ancestral forms
      sufficient for codon-directed synthesis of nonrandom peptides. By tracing aaRS
      catalytic activities back to simpler ancestral peptides, we demonstrate key steps
      for a simpler and hence more probable peptide.RNA development of rapid coding
      systems matching amino acids with anticodon trinucleotides. 

PMID- 23867457
TI  - Neurogenin3 activation is not sufficient to direct duct-to-beta cell
      transdifferentiation in the adult pancreas.
AB  - It remains controversial whether adult pancreatic ducts harbor facultative beta
      cell progenitors. Because neurogenin3 (Ngn3) is a key determinant of pancreatic
      endocrine cell neogenesis during embryogenesis, many studies have also relied
      upon Ngn3 expression as evidence of beta cell neogenesis in adults. Recently,
      however, Ngn3 as a marker of adult beta cell neogenesis has been called into
      question by reports of Ngn3 expression in fully-developed beta cells.
      Nevertheless, direct evidence as to whether Ngn3 activation in adult pancreatic
      duct cells may lead to duct-to-beta cell transdifferentiation is lacking. Here we
      studied two models of Ngn3 activation in adult pancreatic duct cells (low-dose
      alloxan treatment and pancreatic duct ligation) and lineage-traced Ngn3-activated
      duct cells by labeling them through intraductal infusion with a cell-tagging dye,
      CFDA-SE No dye-labeled beta cells were found during the follow-up in either
      model, suggesting that activation of Ngn3 in duct cells is not sufficient to
      direct their transdifferentiation into beta cells. Therefore, Ngn3 activation in
      duct cells is not a signature for adult beta cell neogenesis. 

PMID- 23867456
TI  - Early secreted antigenic target of 6 kDa (ESAT-6) protein of Mycobacterium
      tuberculosis induces interleukin-8 (IL-8) expression in lung epithelial cells via
      protein kinase signaling and reactive oxygen species.
AB  - Early secreted antigenic target of 6 kDa (ESAT-6) of Mycobacterium tuberculosis
      is critical for the virulence and pathogenicity of M. tuberculosis. IL-8, a major
      chemotactic cytokine for neutrophils and T lymphocytes, plays important roles in
      the development of lung injury. To further understand the role of ESAT-6 in lung
      pathology associated with tuberculosis development, we studied the effects of
      ESAT-6 on the regulation of IL-8 expression in lung epithelial cells. ESAT-6
      induced IL-8 expression by increasing IL-8 gene transcription and mRNA stability.
      ESAT-6 induction of IL-8 promoter activity was dependent on nuclear factor-kappaB
      (NF-kappaB) and activator protein-1 (AP-1) binding and sensitive to
      pharmacological inhibition of PKC and ERK and p38 MAPK pathways. ESAT-6 activated
      ERK and p38 MAPK phosphorylation and rapidly induced reactive oxygen species
      (ROS) production. Dimethylthiourea but not mannitol inhibited IL-8 induction by
      ESAT-6, further supporting the involvement of ROS in the induction of IL-8
      expression. Exposure of mice to ESAT-6 induced localized inflammatory cell
      aggregate formation with characteristics of early granuloma concomitant with
      increased keratinocyte chemoattractant CXCL1 staining in bronchiolar and alveolar
      type II epithelial cells and alveolar macrophages. Our studies have identified a
      signal transduction pathway involving ROS, PKC, ERK, and p38 MAPKs and NF-kappaB
      and AP-1 in the ESAT-6 induction of IL-8 expression in lung epithelial cells.
      This has important implications for the understanding of lung innate immune
      responses to tuberculosis and the pathogenesis of lung injury in tuberculosis. 

PMID- 23867458
TI  - Actin dynamics regulated by the balance of neuronal Wiskott-Aldrich syndrome
      protein (N-WASP) and cofilin activities determines the biphasic response of
      glucose-induced insulin secretion.
AB  - Actin dynamics in pancreatic beta-cells is involved in insulin secretion.
      However, the molecular mechanisms of the regulation of actin dynamics by
      intracellular signals in pancreatic beta-cells and its role in phasic insulin
      secretion are largely unknown. In this study, we elucidate the regulation of
      actin dynamics by neuronal Wiskott-Aldrich syndrome protein (N-WASP) and cofilin
      in pancreatic beta-cells and demonstrate its role in glucose-induced insulin
      secretion (GIIS). N-WASP, which promotes actin polymerization through activation
      of the actin nucleation factor Arp2/3 complex, was found to be activated by
      glucose stimulation in insulin-secreting clonal pancreatic beta-cells (MIN6-K8
      beta-cells). Introduction of a dominant-negative mutant of N-WASP, which lacks G
      actin and Arp2/3 complex-binding region VCA, into MIN6-K8 beta-cells or knockdown
      of N-WASP suppressed GIIS, especially the second phase. We also found that
      cofilin, which severs F-actin in its dephosphorylated (active) form, is converted
      to the phosphorylated (inactive) form by glucose stimulation in MIN6-K8 beta
      cells, thereby promoting F-actin remodeling. In addition, the dominant-negative
      mutant of cofilin, which inhibits activation of endogenous cofilin, or knockdown
      of cofilin reduced the second phase of GIIS. However, the first phase of GIIS
      occurs in the G-actin predominant state, in which cofilin activity predominates
      over N-WASP activity. Thus, actin dynamics regulated by the balance of N-WASP and
      cofilin activities determines the biphasic response of GIIS. 

PMID- 23867459
TI  - Engineered soluble monomeric IgG1 CH3 domain: generation, mechanisms of function,
      and implications for design of biological therapeutics.
AB  - Most of the therapeutic antibodies approved for clinical use are full-size IgG1
      molecules. The interaction of the IgG1 Fc with the neonatal Fc receptor (FcRn)
      plays a critical role in maintaining their long half-life. We have hypothesized
      that isolated Fc domains could be engineered to functionally mimic full-size IgG1
      (nanoantibodies) but with decreased (10-fold) size. Here, we report for the first
      time the successful generation of a soluble, monomeric CH3 domain (mCH3). In
      contrast to the wild-type dimeric CH3, the mCH3 exhibited pH-dependent binding to
      FcRn similar to that of Fc. The binding free energy of mCH3 to FcRn was higher
      than that of isolated CH2 but lower than that of Fc. Therefore, CH3 may
      contribute a larger portion of the free energy of binding to FcRn than CH2. A
      fusion protein of mCH3 with an engineered antibody domain (m36.4) also bound to
      FcRn in a pH-dependent fashion and exhibited significantly higher neutralizing
      activity against HIV-1 than m36.4-Fc fusion proteins. The m36.4-mCH3 fusion
      protein was monomeric, stable, soluble, and expressed at a high level in
      Escherichia coli. We also found that engineering an additional disulfide bond in
      mCH3 remarkably increased its thermal stability, whereas the FcRn binding was not
      affected. These data suggest that mCH3 could not only help in the exploration of
      the dual mechanisms of the CH3 contribution to Fc functions (dimerization and
      FcRn interactions) but could also be used for the development of candidate
      therapeutics with optimized half-life, enhanced tissue penetration, access to
      sterically restricted binding sites, and increased therapeutic efficacy. 

PMID- 23867460
TI  - Low-density lipoprotein receptor-related protein 1 (LRP1)-dependent cell
      signaling promotes axonal regeneration.
AB  - Low-density lipoprotein receptors (LRPs) are present extensively on cells outside
      of the nervous system and classically exert roles in lipoprotein metabolism. It
      has been reported recently that LRP1 activation could phosphorylate the
      neurotrophin receptor TrkA in PC12 cells and increase neurite outgrowth from
      developing cerebellar granule cells. These intriguing findings led us to explore
      the hypothesis that LRP1 activation would activate canonical neurotrophic factor
      signaling in adult neurons and promote axonal regeneration after spinal cord
      injury. We now find that treatment of adult rat dorsal root ganglion neurons in
      vitro with LRP1 agonists (the receptor binding domain of alpha-2-macroglobulin or
      the hemopexin domain of matrix metalloproteinase 9) induces TrkC, Akt, and ERK
      activation; significantly increases neurite outgrowth (p < 0.01); and overcomes
      myelin inhibition (p < 0.05). These effects require Src family kinase activation,
      a classic LRP1-mediated Trk transactivator. Moreover, intrathecal infusions of
      LRP1 agonists significantly enhance sensory axonal sprouting and regeneration
      after spinal cord injury in rats compared with control-infused animals (p <
      0.05). A significant role is established for lipoprotein receptors in sprouting
      and regeneration after CNS injury, identifying a novel class of therapeutic
      targets to explore for traumatic neurological disorders. 

PMID- 23867461
TI  - Derlin2 protein facilitates HRD1-mediated retro-translocation of sonic hedgehog
      at the endoplasmic reticulum.
AB  - Endoplasmic reticulum-associated degradation (ERAD) is an important system that
      eliminates misfolded proteins from the ER. Three derlins have been implicated in
      this process, but their precise function remains unknown. In this study, we
      report that although both derlin1 and derlin2 are capable of binding the ERAD
      specific ubiquitin ligase HRD1, they associate with the HRD1-containing complex
      with different affinities. Accordingly, these derlins have nonredundant functions
      in ERAD with derlin2 being an essential functional partner for HRD1-mediated ERAD
      of SHH and NHK. We show that derlin2, but not derlin1 or derlin3, is required for
      ERAD of both glycosylated and nonglycosylated SHH, as well as NHK. Derlin2
      appears to act at a post-targeting step for HRD1-dependent retro-translocation.
      Without derlin2, the assembly of HRD1 into a functional retro-translocation homo
      oligomer proceeds normally, and substrate targeting to the HRD1 complex also
      occurs. However, the ERAD substrate SHH-C is largely trapped inside the ER lumen.
      These observations raise the possibility that derlin2 may regulate the movement
      of substrates through the HRD1-containing retro-translocon. Our study is the
      first to report that derlin2 functions with HRD1 in ERAD of certain substrates
      independent of their glycosylation status. The mammalian ERAD system may require
      multiple derlins that each functions with a distinct E3 partner to eliminate a
      specific subset of substrates. This is different from the model in Saccharomyces
      cerevisiae, in which Hrd1p alone is sufficient for retro-translocation. 

PMID- 23867462
TI  - Fused in sarcoma (FUS) protein lacking nuclear localization signal (NLS) and
      major RNA binding motifs triggers proteinopathy and severe motor phenotype in
      transgenic mice.
AB  - Dysfunction of two structurally and functionally related proteins, FUS and TAR
      DNA-binding protein of 43 kDa (TDP-43), implicated in crucial steps of cellular
      RNA metabolism can cause amyotrophic lateral sclerosis (ALS) and certain other
      neurodegenerative diseases. The proteins are intrinsically aggregate-prone and
      form non-amyloid inclusions in the affected nervous tissues, but the role of
      these proteinaceous aggregates in disease onset and progression is still
      uncertain. To address this question, we designed a variant of FUS, FUS 1-359,
      which is predominantly cytoplasmic, highly aggregate-prone, and lacks a region
      responsible for RNA recognition and binding. Expression of FUS 1-359 in neurons
      of transgenic mice, at a level lower than that of endogenous FUS, triggers
      FUSopathy associated with severe damage of motor neurons and their axons,
      neuroinflammatory reaction, and eventual loss of selective motor neuron
      populations. These pathological changes cause abrupt development of a severe
      motor phenotype at the age of 2.5-4.5 months and death of affected animals within
      several days of onset. The pattern of pathology in transgenic FUS 1-359 mice
      recapitulates several key features of human ALS with the dynamics of the disease
      progression compressed in line with shorter mouse lifespan. Our data indicate
      that neuronal FUS aggregation is sufficient to cause ALS-like phenotype in
      transgenic mice. 

PMID- 23867463
TI  - Autoxidation and oxygen binding properties of recombinant hemoglobins with
      substitutions at the alphaVal-62 or betaVal-67 position of the distal heme
      pocket.
AB  - The E11 valine in the distal heme pocket of either the alpha- or beta-subunit of
      human adult hemoglobin (Hb A) was replaced by leucine, isoleucine, or
      phenylalanine. Recombinant proteins were expressed in Escherichia coli and
      purified for structural and functional studies. (1)H NMR spectra were obtained
      for the CO and deoxy forms of Hb A and the mutants. The mutations did not disturb
      the alpha1beta2 interface in either form, whereas the H-bond between alphaHis-103
      and betaGln-131 in the alpha1beta1 interfaces of the deoxy alpha-subunit mutants
      was weakened. Localized structural changes in the mutated heme pocket were
      detected for the CO form of recombinant Hb (rHb) (alphaV62F), rHb (betaV67I), and
      rHb (betaV67F) compared with Hb A. In the deoxy form the proximal histidyl
      residue in the beta-subunit of rHb (betaV67F) has been altered. Furthermore, the
      interactions between the porphyrin ring and heme pocket residues have been
      perturbed in rHb (alphaV62I), rHb (alphaV62F), and rHb (betaV67F). Functionally,
      the oxygen binding affinity (P50), cooperativity (n50), and the alkaline Bohr
      Effect of the three alpha-subunit mutants and rHb (betaV67L) are similar to those
      of Hb A. rHb (betaV67I) and rHb (betaV67F) exhibit low and high oxygen affinity,
      respectively. rHb (betaV67F) has P50 values lower that those reported for rHb
      (alphaL29F), a B10 mutant studied previously in our laboratory (Wiltrout, M. E.,
      Giovannelli, J. L., Simplaceanu, V., Lukin, J. A., Ho, N. T., and Ho, C. (2005)
      Biochemistry 44, 7207-7217). These E11 mutations do not slow down the
      autoxidation and azide-induced oxidation rates of the recombinant proteins.
      Results from this study provide new insights into the roles of E11 mutants in the
      structure-function relationship in hemoglobin. 

PMID- 23867464
TI  - Novel HLA-B27-restricted epitopes from Chlamydia trachomatis generated upon
      endogenous processing of bacterial proteins suggest a role of molecular mimicry
      in reactive arthritis.
AB  - Reactive arthritis (ReA) is an HLA-B27-associated spondyloarthropathy that is
      triggered by diverse bacteria, including Chlamydia trachomatis, a frequent
      intracellular parasite. HLA-B27-restricted T-cell responses are elicited against
      this bacterium in ReA patients, but their pathogenetic significance, autoimmune
      potential, and relevant epitopes are unknown. High resolution and sensitivity
      mass spectrometry was used to identify HLA-B27 ligands endogenously processed and
      presented by HLA-B27 from three chlamydial proteins for which T-cell epitopes
      were predicted. Fusion protein constructs of ClpC, Na(+)-translocating NADH
      quinone reductase subunit A, and DNA primase were expressed in HLA-B27(+) cells,
      and their HLA-B27-bound peptidomes were searched for endogenous bacterial
      ligands. A non-predicted peptide, distinct from the predicted T-cell epitope, was
      identified from ClpC. A peptide recognized by T-cells in vitro, NQRA(330-338),
      was detected from the reductase subunit. This is the second HLA-B27-restricted T
      cell epitope from C. trachomatis with relevance in ReA demonstrated to be
      processed and presented in live cells. A novel peptide from the DNA primase,
      DNAP(211-223), was also found. This was a larger variant of a known epitope and
      was highly homologous to a self-derived natural ligand of HLA-B27. All three
      bacterial peptides showed high homology with human sequences containing the
      binding motif of HLA-B27. Molecular dynamics simulations further showed a
      striking conformational similarity between DNAP(211-223) and its homologous and
      much more flexible human-derived HLA-B27 ligand. The results suggest that
      molecular mimicry between HLA-B27-restricted bacterial and self-derived epitopes
      is frequent and may play a role in ReA. 

PMID- 23867466
TI  - Possible role of adrenomedullin and nitric oxide in major depression.
AB  - Adrenomedullin (ADM) and nitric oxide (NO) have been implicated in the
      pathogenesis of certain psychiatric disorders such as schizophrenia and bipolar
      disorder. ADM induces vasorelaxation by activating adenylate cyclase and
      stimulating the release of NO. These two molecules are known to influence
      cerebral activity. In this study, we aimed to examine the serum levels of ADM and
      NO in patients with major depression (MD). We enrolled 50 patients with MD and 50
      healthy control subjects. The diagnosis of MD was established on the basis of a
      structured clinical interview using the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (DSM-IV). The severity of depressive symptoms
      was evaluated using Hamilton's 17-item Depression Rating Scale. The mean serum
      levels of ADM and NO in patients with MD were significantly higher than those in
      healthy subjects (p=0.001, for both). The severity of psychomotor retardation in
      patients with MD was significantly correlated with the ADM (r=0.37, p=0.007) and
      NO levels (r=0.29, p=0.038). The patients with obvious psychomotor retardation
      had significantly higher levels of ADM and NO than did the patients with no
      psychomotor retardation (p=0.025, p=0.030). A significantly positive correlation
      was found between ADM and NO levels in patients with MD (r=0.79, p=0.001). Serum
      levels of ADM and NO levels were not correlated with the severity or duration of
      depression or depressive symptoms (except psychomotor retardation). In
      conclusion, our study indicates that serum levels of ADM and NO are elevated in
      patients with MD and that increased serum levels of ADM and NO may be associated
      with psychomotor retardation. The ADM-NO system may serve as a new target in the
      treatment of patients with MD and psychomotor retardation. 

PMID- 23867465
TI  - Heparan sulfate proteoglycans containing a glypican 5 core and 2-O-sulfo-iduronic
      acid function as Sonic Hedgehog co-receptors to promote proliferation.
AB  - Sonic Hedgehog (Shh) signaling is crucial for growth, cell fate determination,
      and axonal guidance in the developing nervous system. Although the receptors
      Patched (Ptch1) and Smoothened (Smo) are required for Shh signaling, a number of
      distinct co-receptors contribute to these critical responses to Shh. Several
      membrane-embedded proteins such as Boc, Cdo, and Gas1 bind Shh and promote
      signaling. In addition, heparan sulfate proteoglycans (HSPGs) have also been
      implicated in the initiation of Shh responses. However, the attributes of HSPGs
      that function as co-receptors for Shh have not yet been defined. Here, we
      identify HSPGs containing a glypican 5 core protein and 2-O-sulfo-iduronic acid
      residues at the nonreducing ends of the glycans as co-receptors for Shh. These
      HSPG co-receptors are expressed by cerebellar granule cell precursors and promote
      Shh binding and signaling. At the subcellular level, these HSPG co-receptors are
      located adjacent to the primary cilia that act as Shh signaling organelles. Thus,
      Shh binds to HSPG co-receptors containing a glypican 5 core and 2-O-sulfo
      iduronic acid to promote neural precursor proliferation. 

PMID- 23867467
TI  - Participation of the central p38 and ERK1/2 pathways in IL-1beta-induced
      sensitization of nociception in rats.
AB  - This study examined the participation of central mitogen-activated protein
      kinases (MAPKs) in the central sensitization produced by a subcutaneous injection
      of interleukin-1beta (IL-1beta) in male Sprague-Dawley rats. Formalin-induced
      responses were evaluated 24h after an IL-1beta injection. A subcutaneous
      injection of 10ng of IL-1beta elevated the formalin-induced scratching response
      significantly in the second phase compared to the vehicle-treated group.
      Pretreatment with an IL-1 receptor antagonist reduced the IL-1beta-induced
      sensitization. Pretreatment with IL-1beta increased the p-ERK and p-p38
      expression induced by the formalin injection. Double immunofluorescence data
      revealed increases in phospho-extracellular signal-regulated kinase (p-ERK)
      immunoreactive cells that co-localize with neuronal nuclei (NeuN), a neuronal
      marker, and in phospho-p38 (p-p38) immunoreactive cells that co-localize with
      NeuN and OX42, a microglia marker. The intracisternal administration of
      minocycline (50MUg), a microglia inhibitor, attenuated the increased formalin
      induced scratching responses in the IL-1beta-treated rats. The intracisternal
      administration of PD98059 (1, 10MUg), a MEK inhibitor, and SB203580 (1, 5MUg), a
      p38 inhibitor, also attenuated the number of formalin-induced scratches in the
      second phase in the IL-1beta-treated rats. These results suggest that the IL
      1beta-induced central sensitization of nociception is mediated by the central
      MAPK pathways, which are activated differentially in the neurons and microglia
      under inflammatory pain conditions. Therefore, blockade of the MAPK pathways can
      be as a potential therapeutic target for the central sensitization of
      inflammatory pain. 

PMID- 23867469
TI  - Tumor microenvironmental conversion of natural killer cells into myeloid-derived
      suppressor cells.
AB  - How myeloid-derived suppressor cells (MDSC) emerge in the tumor environment
      remains unclear. Here, we report that GM-CSF can convert natural killer (NK)
      cells into MDSCs. When transferred into tumor-bearing mice, adoptively
      transferred NK cells lost their NK phenotype and were converted into
      Ly6C(high)Ly6G(high) MDSC. This conversion was abolished by exposure to IL-2
      either in vitro or in vivo. Notably, we found that of the 4 maturation stages
      based on CD11b/CD27 expression levels, only the CD11b(high)CD27(high) NK cells
      could be converted into CD11b(+)Gr1(+) MDSC ex vivo. Transfer of CD27(high) NK
      cells from tumor-bearing mice into tumor-bearing recipients was associated with
      conversion to MDSC in a manner associated with reduced numbers of
      CD11b(high)CD27(high) and CD11b(high)CD27(low) NK cell populations in the
      recipients. Our results identify a pathway of MDSC development from immature NK
      cells in tumor-bearing hosts, providing new insights into how tumor cells
      modulate their host immune microenvironment to escape immune surveillance.

PMID- 23867471
TI  - Stem cell differentiation and lumen formation in colorectal cancer cell lines and
      primary tumors.
AB  - Single cancer stem-like cells (CSC) from colorectal cancers can be functionally
      identified by their ability to form large lumen-containing colonies in three
      dimensional Matrigel cultures. These colonies contain the three types of
      differentiated colorectal epithelial cells, and single cells obtained from them
      can reproduce themselves and form tumors efficiently in immunodeficient mice. In
      this study, we show how hypoxia affects these CSC-derived lumens to control
      differentiation of stem-like cells and enterocytes via the homeobox gene CDX1.
      Lumens were identified by F-actin staining and they expressed many
      characteristics associated with normal differentiated intestinal epithelium,
      including brush border enzymes, polarization, and tight junctions. RNA
      interference-mediated silencing of CDX1 reduced lumen formation. Inhibitory
      effects of hypoxia on lumen formation and stem cell differentiation, including
      suppression of CDX1 expression, could be mimicked by inhibiting prolyl
      hydroxylases that activate HIF1, suggesting that HIF1 is a critical mediator of
      the effects of hypoxia in this setting. Cell line-derived lumens were
      phenotypically indistinguishable from colorectal tumor glandular structures used
      by pathologists to grade tumor differentiation. Parallel results to those
      obtained with established cell lines were seen with primary cultures from fresh
      tumors. This in vitro approach to functional characterization of CSCs and their
      differentiation offers a valid model to study colorectal tumor differentiation
      and differentiation of colorectal CSCs, with additional uses to enable high
      throughput screening for novel anticancer compounds.

PMID- 23867470
TI  - MUC1 is a potential target for the treatment of acute myeloid leukemia stem
      cells.
AB  - Acute myeloid leukemia (AML) is a malignancy of stem cells with an unlimited
      capacity for self-renewal. MUC1 is a secreted, oncogenic mucin that is expressed
      aberrantly in AML blasts, but its potential uses to target AML stem cells have
      not been explored. Here, we report that MUC1 is highly expressed on AML
      CD34(+)/lineage(-)/CD38(-) cells as compared with their normal stem cell
      counterparts. MUC1 expression was not restricted to AML CD34(+) populations as
      similar results were obtained with leukemic cells from patients with CD34(-)
      disease. Engraftment of AML stem cell populations that highly express MUC1
      (MUC1(high)) led to development of leukemia in NOD-SCID IL2Rgamma(null) (NSG)
      immunodeficient mice. In contrast, MUC1(low) cell populations established normal
      hematopoiesis in the NSG model. Functional blockade of the oncogenic MUC1-C
      subunit with the peptide inhibitor GO-203 depleted established AML in vivo, but
      did not affect engraftment of normal hematopoietic cells. Our results establish
      that MUC1 is highly expressed in AML stem cells and they define the MUC1-C
      subunit as a valid target for their therapeutic eradication.

PMID- 23867472
TI  - Rapid induction of lung adenocarcinoma by fibroblast growth factor 9 signaling
      through FGF receptor 3.
AB  - Fibroblast growth factors (FGF) are expressed in many non-small cell lung
      carcinoma (NSCLC) primary tumors and derived cell lines, and mutations in FGF
      receptor 3 (FGFR3) have been identified in human lung adenocarcinoma. FGF9 has
      been implicated in the pathogenesis of NSCLC by synergizing with EGFR pathways or
      by providing an escape pathway mediating resistance to EGFR inhibition. To model
      pathogenic mechanisms mediated by FGF signals, we have established a mouse model
      in which FGF9 expression can be induced in adult lung epithelium. Here, we show
      that induced expression of FGF9 in adult lung leads to the rapid proliferation of
      distal airway epithelial cells that express the stem cell marker, Sca-1, and the
      proximal and distal epithelial markers, Sftpc and CC10, the rapid formation of
      Sftpc-positive adenocarcinomas, and eventual metastasis in some mice.
      Furthermore, we have identified FGFR3 as the obligate receptor mediating the FGF9
      oncogenic signal. These results identify an FGF9-FGFR3 signal as a primary
      oncogenic pathway for lung adenocarcinoma and suggest that this pathway could be
      exploited for customized therapeutic applications for both primary tumors and
      those that have acquired resistance to inhibition of other signaling pathways.

PMID- 23867474
TI  - Reg3beta deficiency impairs pancreatic tumor growth by skewing macrophage
      polarization.
AB  - The lectin Reg3beta provides crucial protection to various tissues against
      inflammation, a potential risk factor for pancreatic ductal adenocarcinoma.
      Reg3beta is also overexpressed in serum and pancreatic juice from patients with
      this cancer, but its function in this context remains to be elucidated. In this
      study, we investigated the role of Reg3beta in tumor development in an orthotopic
      mouse model of pancreatic cancer. Reg3beta deletion in mice drastically impaired
      pancreatic tumor growth, correlating with decreased angiogenesis and increased
      apoptosis of tumor cells. Moreover, Reg3beta deficiency resulted in an alteration
      of the tumoral immune microenvironment, reflected by a decrease in the M2/M1
      ratio of tumor-associated macrophages and an upregulation of CD3(+) cell
      infiltration. Addition of Reg3beta to prestimulated RAW 264.7 or primary
      macrophages enhanced M2 polarization through the activation of STAT3 signaling
      pathway. Conditioned media from Reg3beta-M2-polarized primary macrophages
      inhibited apoptosis and prolonged the viability of Panc02 tumor cells. Our
      studies reveal a novel role for Reg3beta as a tumor promoter in pancreatic
      adenocarcinoma through the regulation of tumor stroma. Thus, inhibition of this
      protein may be a useful strategy in treatment of pancreatic cancer.

PMID- 23867475
TI  - SOX2 expression associates with stem cell state in human ovarian carcinoma.
AB  - The SRY-related HMG-box family of transcription factors member SOX2 regulates
      stemness and pluripotency in embryonic stem cells and plays important roles
      during early embryogenesis. More recently, SOX2 expression was documented in
      several tumor types including ovarian carcinoma, suggesting an involvement of
      SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies
      exploring the predictive value of SOX2 protein expression with respect to
      histopathologic and clinical parameters report contradictory results in
      individual tumors, indicating that SOX2 may play tumor-specific roles. In this
      report, we analyze the functional relevance of SOX2 expression in human ovarian
      carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2
      expression increases the expression of CSC markers, the potential to form tumor
      spheres, and the in vivo tumor-initiating capacity, while leaving cellular
      proliferation unaltered. Moreover, SOX2-expressing cells display enhanced
      apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence,
      our data show that SOX2 associates with stem cell state in ovarian carcinoma and
      induction of SOX2 imposes CSC properties on SOC cells. We propose the existence
      of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and
      therapy resistance in human SOC.

PMID- 23867473
TI  - Epimorphin is a novel regulator of the progesterone receptor isoform-a.
AB  - Epimorphin/syntaxin-2 is a membrane-tethered protein localized extracellularly
      (Epim) and intracellularly (Stx-2). The extracellular form Epim stimulates
      morphogenic processes in a range of tissues, including in murine mammary glands
      where its overexpression in luminal epithelial cells is sufficient to drive
      hyperplasia and neoplasia. We analyzed WAP-Epim transgenic mice to gain insight
      into how Epim promotes malignancy. Ectopic overexpression of Epim during
      postnatal mammary gland development led to early side-branching onset, precocious
      bud formation, and increased proliferation of mammary epithelial cells.
      Conversely, peptide-based inhibition of Epim function reduced side branching.
      Because increased side branching and hyperplasia occurs similarly in mice upon
      overexpression of the progesterone receptor isoform-a (Pgr-a), we investigated
      whether Epim exhibits these phenotypes through Pgr modulation. Epim
      overexpression indeed led to a steep upregulation of both total Pgr mRNA and Pgr
      a protein levels. Notably, the Pgr antagonist RU486 abrogated Epim-induced ductal
      side branching, mammary epithelial cell proliferation, and bud formation.
      Evaluation of Epim signaling in a three-dimensional ex vivo culture system showed
      that its action was dependent on binding to its extracellular receptor, integrin
      alphaV, and on matrix metalloproteinase 3 activity downstream of Pgr-a. These
      findings elucidate a hitherto unknown transcriptional regulator of Pgr-a, and
      shed light on how overexpression of Epim leads to malignancy.

PMID- 23867476
TI  - Mammary tumor formation and metastasis evoked by a HER2 splice variant.
AB  - The HER2 gene is amplified and overexpressed in approximately 20% of invasive
      breast cancers where it is associated with metastasis and poor prognosis. Here,
      we describe a constitutively active splice variant of HER2 (Delta-HER2) in human
      mammary epithelial cells that evokes aggressive breast cancer phenotypes. Delta
      HER2 overexpression in mammary epithelial cells was sufficient to reduce
      apoptosis, increase proliferation, and induce expression of mesenchymal markers,
      features that were associated with greater invasive potential in three
      dimensional cultures in vitro and more aggressive tumorigenicity and metastasis
      in vivo. In contrast, overexpression of wild-type HER2 was insufficient at
      evoking such effects. Unbiased protein-tyrosine phosphorylation profiling in
      Delta-HER2-expressing cells revealed increased phosphorylation of several
      signaling proteins not previously known to be controlled by the HER2 pathway.
      Furthermore, microarray expression analysis revealed activation of genes known to
      be highly expressed in ER-negative, high-grade, and metastatic primary breast
      tumors. Together, our results provide mechanistic insights into the activity of a
      highly pathogenic splice variant of HER2.

PMID- 23867478
TI  - Recombinant coagulation factor approved for hemophilia B prophylaxis.

PMID- 23867479
TI  - One year passes for federal innovation awards.

PMID- 23867477
TI  - Werner syndrome helicase has a critical role in DNA damage responses in the
      absence of a functional fanconi anemia pathway.
AB  - Werner syndrome is genetically linked to mutations in WRN that encodes a DNA
      helicase-nuclease believed to operate at stalled replication forks. Using a newly
      identified small-molecule inhibitor of WRN helicase (NSC 617145), we investigated
      the role of WRN in the interstrand cross-link (ICL) response in cells derived
      from patients with Fanconi anemia, a hereditary disorder characterized by bone
      marrow failure and cancer. In FA-D2(-/-) cells, NSC 617145 acted synergistically
      with very low concentrations of mitomycin C to inhibit proliferation in a WRN
      dependent manner and induce double-strand breaks (DSB) and chromosomal
      abnormalities. Under these conditions, ataxia-telangiectasia mutated activation
      and accumulation of DNA-dependent protein kinase, catalytic subunit pS2056 foci
      suggested an increased number of DSBs processed by nonhomologous end-joining
      (NHEJ). Rad51 foci were also elevated in FA-D2(-/-) cells exposed to NSC 617145
      and mitomycin C, suggesting that WRN helicase inhibition interferes with later
      steps of homologous recombination at ICL-induced DSBs. Thus, when the Fanconi
      anemia pathway is defective, WRN helicase inhibition perturbs the normal ICL
      response, leading to NHEJ activation. Potential implication for treatment of
      Fanconi anemia-deficient tumors by their sensitization to DNA cross-linking
      agents is discussed.

PMID- 23867480
TI  - IMS report calls medication misuse a $200 billion problem.

PMID- 23867481
TI  - Impact of outpatient electronic medical record on antiretroviral errors among
      hospitalized patients.

PMID- 23867482
TI  - Tenofovir-related nephrotoxicity: an ongoing clinical challenge.

PMID- 23867483
TI  - Comparative properties of U-500 and U-100 regular human insulin.

PMID- 23867484
TI  - Comparative properties of U-500 and U-100 regular human insulin.

PMID- 23867485
TI  - Implementation of pharmacist-managed anticoagulation in patients receiving newer
      anticoagulants.

PMID- 23867486
TI  - Treatment of clinical aspiration: a reappraisal.
AB  - PURPOSE: The treatment of clinical aspiration is reviewed. SUMMARY: The common
      definition of aspiration is the inhalation of oropharyngeal or gastric contents
      into the larynx and lower respiratory tract. Pulmonary aspiration frequently
      occurs in both the hospital and community settings and can affect patients of all
      ages. Aspiration can often lead to pulmonary complications, which can be divided
      into two main pathophysiological processes: chemical pneumonitis and aspiration
      pneumonia. These processes differ based on the aspirate contents, which
      ultimately dictate the physiological pathway and enduring symptoms. While these
      processes are clearly divergent, the clinical presentation may be
      indistinguishable, often leading to inappropriate or unnecessary treatment.
      Despite the widespread use of antibiotic therapy for aspiration complications,
      the literature supporting this treatment is quite limited. A literature review of
      clinical trials was conducted to address core aspects of aspiration
      complications, including bacteriology and empirical antibiotic treatment. The
      findings reveal that many of the current antibiotic practices used to treat
      clinical aspiration stem from limited studies dating back to the 1970s or before.
      Newer data have begun to refute these standard antibiotic regimens and provide a
      case for tailored empirical treatment. The treatment of aspiration should be
      largely focused on the underlying etiology and tailored to individual patients
      and their symptoms. CONCLUSION: The management of aspiration should largely focus
      on whether the underlying problem is pneumonitis or pneumonia. Recent studies on
      aspiration pneumonia have begun to show a difference in culture-isolated bacteria
      and therefore optimal treatment regimens, compared with pivotal human trials
      completed more than 40 years ago.

PMID- 23867487
TI  - Description of outbreaks of health-care-associated infections related to
      compounding pharmacies, 2000-12.
AB  - PURPOSE: Outbreaks of health-care-associated infections related to compounding
      pharmacies from 2000 through 2012 are described. METHODS: PubMed and the websites
      for the Centers for Disease Control and Prevention and the Food and Drug
      Administration were searched to identify infectious outbreaks associated with
      compounding pharmacies outside the hospital setting between January 2000 and
      November 2012. RESULTS: Between January 2000 and before the 2012 fungal
      meningitis outbreak, 11 outbreaks were identified, involving 207 infected
      patients and 17 deaths after exposure to contaminated compounded drugs. The 2012
      meningitis outbreak had a similar mortality rate but increased these totals
      almost fivefold. Half of the outbreaks involved patients in more than one state.
      Three outbreaks involved ophthalmic drugs. The remaining outbreaks involved
      corticosteroids, heparin flush solutions, cardioplegia solution, i.v. magnesium
      sulfate, total parenteral nutrition, and fentanyl. The outbreaks were caused by
      pathogens commonly associated with health-care-associated infections, common skin
      commensals, and organisms that rarely cause infection. Morbidity was substantial,
      including vision loss. Half the outbreaks resulted in recall of all sterile drugs
      from the pharmacy due to systemic problems with sterile procedures. CONCLUSION:
      Before the nationwide 2012 fungal meningitis outbreak, drugs produced by
      compounding pharmacies were associated with 11 other smaller, but equally
      serious, outbreaks that occurred sporadically over the past 12 years. Lapses in
      sterile compounding procedures led to contamination of compounded drugs, exposure
      to patients, and a threat to public health in these outbreaks. Recognition and
      subsequent public health investigation were usually triggered by the occurrence
      of illness among multiple patients in a single health care setting.

PMID- 23867488
TI  - Comparison of pharmacy services at critical access hospitals and other rural and
      small hospitals in Illinois.
AB  - PURPOSE: The results of a survey evaluating pharmacy services and technology use
      at critical access hospitals (CAHs) and other small and rural hospitals in
      Illinois are reported. METHODS: A mail survey was sent to pharmacy directors at
      86 CAHs and other rural and small hospitals in Illinois not designated as CAHs.
      Independent sample t tests and chi-square statistics were used to compare CAHs
      and non-CAHs in areas such as pharmacy services, staffing, use of technology, and
      sterile compounding practices. RESULTS: The survey response rate was 46.5%, with
      usable data received from 40 hospitals. Analysis of the survey data indicated
      that hospitals designated as CAHs were significantly less likely than non-CAHs to
      have automatic therapeutic interchange policies (p = 0.012) and more likely to
      conduct pharmacist-provided educational programs on medication costs for
      physicians and other health care personnel (p = 0.037). Relative to non-CAHs,
      CAHs were significantly less likely to have automated dispensing cabinets (p =
      0.016) and to out-source the preparation of sterile products to offsite vendors
      (p = 0.012); pharmacy directors at CAHs were less likely to report the use of
      technology for remote medication order entry or review (p = 0.038). At both types
      of facilities, pharmacists typically have both distributive and clinical
      responsibilities, and patient-specific clinical pharmacy services (e.g., patient
      education or counseling, other drug therapy monitoring, medication
      reconciliation, pharmacokinetic consultations) are offered at similar
      frequencies. CONCLUSION: A survey of pharmacy departments at small and rural
      hospitals in Illinois determined that there were more similarities than
      differences between CAHs and non-CAHs. The survey indicated significant
      differences in dispensing processes, the use of technology and drug policy tools,
      and outsourcing of sterile product preparation.

PMID- 23867489
TI  - Comparison of a hybrid medication distribution system to simulated decentralized
      distribution models.
AB  - PURPOSE: The results of a study to estimate the human resource and cost
      implications of changing the medication distribution model at a large medical
      center are presented. METHODS: A two-part study was conducted to evaluate
      alternatives to the hospital's existing hybrid distribution model (64% of doses
      dispensed via cart fill and 36% via automated dispensing cabinets [ADCs]). An
      assessment of nurse, pharmacist, and pharmacy technician workloads within the
      hybrid system was performed through direct observation, with time standards
      calculated for each dispensing task; similar time studies were conducted at a
      comparator hospital with a decentralized medication distribution system involving
      greater use of ADCs. The time study data were then used in simulation modeling of
      alternative distribution scenarios: one involving no use of cart fill, one
      involving no use of ADCs, and one heavily dependent on ADC dispensing (89% via
      ADC and 11% via cart fill). RESULTS: Simulation of the base-case and alternative
      scenarios indicated that as the modeled percentage of doses dispensed from ADCs
      rose, the calculated pharmacy technician labor requirements decreased, with a
      proportionately greater increase in the nursing staff workload. Given that nurses
      are a higher-cost resource than pharmacy technicians, the projected human
      resource opportunity cost of transitioning from the hybrid system to a
      decentralized system similar to the comparator facility's was estimated at
      $229,691 per annum. CONCLUSION: Based on the simulation results, it was decided
      that a transition from the existing hybrid medication distribution system to a
      more ADC-dependent model would result in an unfavorable shift in staff skill mix
      and corresponding human resource costs at the medical center.

PMID- 23867490
TI  - Stability of dexmedetomidine in polyvinyl chloride bags containing 0.9% sodium
      chloride injection.
AB  - PURPOSE: The stability of dexmedetomidine in polyvinyl chloride (PVC) bags
      containing 0.9% sodium chloride injection was studied. METHODS: Dexmedetomidine
      solutions (4, 8, 12, and 20 MUg/mL; n = 6 for each) were prepared by removing 2,
      4, 6, and 10 mL of 0.9% sodium chloride injection, respectively, from 50-mL PVC
      bags and injecting 2, 4, 6, and 10 mL of dexmedetomidine 100 MUg/mL,
      respectively. To ensure a homogeneous mixture, the contents of each bag was
      manually mixed initially and before each sample was removed. All compounding was
      conducted by a single pharmacist using aseptic technique in a horizontal-laminar
      airflow hood at 25  degrees C. Forced-degradation studies were conducted at 70 +/
      1  degrees C. Stability samples were analyzed using high-performance liquid
      chromatography electrospray ionization-tandem mass spectrometry (LC/MS-MS) and
      high-performance liquid chromatography-ultraviolet-light (HPLC/UV) absorbance.
      Forced-degradation samples were monitored using LC/MS-MS, HPLC/UV, and gas
      chromatography-MS. RESULTS: Dexmedetomidine solutions were very stable at 23 +/-
      2  degrees C at all four concentrations over the 48-hour testing period. As
      determined via LC/MS-MS and HPLC/UV methods, over 97% of the initial
      concentration of dexmedetomidine remained after 48 hours. Extensive HPLC/UV
      active degradation products could be observed in basic conditions; only minor UV
      active degradation products were observed in acidic, oxidative, and photochemical
      conditions. CONCLUSION: Dexmedetomidine hydrochloride 4, 8, 12, and 20 MUg/mL
      stored in PVC bags at 23 +/- 2  degrees C was stable for 48 hours, despite a
      slight decrease in solution pH seen with increasing dexmedetomidine
      concentrations.

PMID- 23867491
TI  - Comparison of the timing of initial prophylactic palivizumab dosing on
      hospitalization of neonates for respiratory syncytial virus.
AB  - PURPOSE: The effects of two prophylactic palivizumab schedules on hospitalization
      of neonates for respiratory syncytial virus (RSV) were compared. METHODS: This
      retrospective study was conducted in the neonatal intensive care unit (NICU) of a
      tertiary care, academic medical center. Patients were divided into two groups.
      Group 1 (hospitalized between October 2005 and April 2007) received inpatient
      doses of palivizumab monthly throughout the RSV season, regardless of their
      anticipated discharge date, followed by outpatient doses. Group 2 (hospitalized
      between October 2007 and April 2009) received only one dose of palivizumab before
      hospital discharge with subsequent outpatient doses. The primary outcome measure
      was the number of hospitalizations for RSV bronchiolitis. Secondary endpoints
      included the total number of palivizumab doses each patient received, number of
      inpatient doses per patient, number of hospitalizations requiring intensive care
      unit admission, patient need for mechanical ventilation, outcome of the RSV
      related hospitalization, and cost of inpatient palivizumab doses per patient.
      RESULTS: A total of 207 neonates were included in the study (112 in group 1, 95
      in group 2). The mean gestational age was 29.7 weeks in group 1 and 30.3 weeks in
      group 2. Seven patients were hospitalized for RSV infection (5 in group 1 versus
      2 in group 2, p = 0.4564). No RSV-related deaths occurred. Significantly more
      inpatient doses were administered to group 1 versus group 2 (1.7 versus 1, p <
      0.001). Limiting inpatient palivizumab to 1 dose before discharge resulted in an
      institutional cost savings of more than $60,000 annually. CONCLUSION:
      Hospitalization rates for RSV did not significantly differ between NICU patients
      who received inpatient prophylactic palivizumab monthly and those who received
      only one dose before discharge.

PMID- 23867492
TI  - Opportunities for pharmacists in mobile health.

PMID- 23867493
TI  - Temporal expression patterns of rainbow trout immune-related genes in response to
      Myxobolus cerebralis exposure.
AB  - Infection of salmonids by the myxozoan parasite Myxobolus cerebralis can cause
      whirling disease, which is responsible for high mortalities in rainbow trout
      hatcheries and natural populations in the United States. Although considerable
      research has provided insight into disease pathology, host invasion, and
      inheritance patterns of resistance, the causal genetic variants and molecular
      mechanisms underlying host resistance or susceptibility remain elusive. A
      previous study found that expression changes of specific metallothionein genes
      following M. cerebralis infection are implicated in whirling disease resistance.
      The present study examines the dynamic transcriptional response to infection of
      several upstream regulators of the metallothionein gene family (IL-1beta, KLF2,
      STAT3, STAT5), along with innate immune response genes (IFN-gamma, IRF1 and
      iNOS). Pathogen loads and gene expression were compared across multiple time
      points after M. cerebralis exposure to elucidate how resistant and susceptible
      rainbow trout strains transcriptionally respond to early invasion. IL-1beta, IFN
      gamma, IRF1, and iNOS all showed increased expression following M. cerebralis
      exposure for one or both strains across multiple time points. The interferon
      related genes IFN-gamma and IRF1 had consistently increased expression in the
      susceptible strain in comparison to the resistant strain, likely due to a less
      effective initial immune response. STAT3 was the only gene with consistently
      increased expression in the resistant strain following infection while remaining
      unchanged in the susceptible strain. Given its pleiotropic effects on immune
      response, STAT3 is an excellent candidate for future research of whirling disease
      resistance mechanisms.

PMID- 23867494
TI  - Interaction between Kazal serine proteinase inhibitor SPIPm2 and viral protein
      WSV477 reduces the replication of white spot syndrome virus.
AB  - White spot syndrome (WSS) is a viral disease caused by white spot syndrome virus
      (WSSV) which leads to severe mortality in cultured penaeid shrimp. In response to
      WSSV infection in Penaeus monodon, a Kazal serine proteinase inhibitor SPIPm2,
      normally stored in the granules of granular and semi-granular hemocytes is up
      regulated and found to deter the viral replication. By using yeast two-hybrid
      screening, we have identified a viral target protein, namely WSV477. Instead of
      being a proteinase, the WSV477 was reported to be a Cys2/Cys2-type zinc finger
      regulatory protein having ATP/GTP-binding activity. In vitro pull down assay
      confirmed the protein-protein interaction between rSPIPm2 and rWSV477. Confocal
      laser scanning microscopy demonstrated that the SPIPm2 and WSV477 were co
      localized in the cytoplasm of shrimp hemocytes. Using RNA interference, the
      silencing of WSV477 resulted in down-regulated of viral late gene VP28, the same
      result obtained with SPIPm2. In this instance, the SPIPm2 does not function as
      proteinase inhibitor but inhibit the regulatory function of WSV477.

PMID- 23867495
TI  - Expression and function analysis of Rac1 homolog in Chinese shrimp Fenneropenaeus
      chinensis.
AB  - Rac1 is a ubiquitous GTP-binding protein that plays a crucial role in multiple
      cellular processes. In the present study, a Rac1 homolog (FcRac1) was cloned from
      the Chinese shrimp Fenneropenaeus chinensis. The open reading frame (ORF) of
      FcRac1 consists of 579 bp encoding 192 aa. The predicted molecular weight (MW) of
      the deduced amino acid sequence of FcRac1 was 21.46 kDa, and its theoretical pI
      was 8.62. Homology analysis showed that the amino acid sequence of Rac1 had high
      conservation among those from different species. Phylogenetic analysis showed
      that FcRac1 closely related to Rac1 proteins from other arthropods. FcRac1 showed
      the highest expression level in the hemocytes. In situ hybridization detection
      showed that it distributed in all types of hemocytes. Recombinant protein of
      FcRac1 showed apparent activity of GTPase. The transcription of FcRac1 in
      juvenile shrimp changed after bacteria or WSSV challenge. The present data
      suggests that FcRac1 might play important roles in the innate immunity of shrimp.

PMID- 23867496
TI  - Effect of a hemiuroid trematode on the hemocyte immune parameters of the cockle
      Anadara trapezia.
AB  - When a trematode parasite penetrates a potential molluscan host, it has to
      circumvent the host's internal defense system. In molluscs, the primary effector
      cells of this system are the hemocytes which orchestrate many of the cellular and
      humoral immune functions. Survival of the parasite can occur only in the absence
      of a successful immune response, and continued development only if the host is
      physiologically suitable. This study investigated hemocytic response against
      asexual stages of a hemiuroid trematode by its host, the marine bivalve Anadara
      trapezia. Hemocyte characteristic (type, morphology) and function (mortality,
      phagocytosis and oxidative activity) were analyzed by flow cytometry in
      parasitized and non-parasitized cockles. A. trapezia possesses two types of
      hemocytes: amebocytes and erythrocytes. Analysis of histological section showed
      that there was no host hemocytic response around hemiuroid sporocysts. The
      infection induced a significant increase of the total circulating hemocytes with
      a higher proportion of erythrocytes relative to amebocytes, coupled with a lower
      phagocytosis rate and a statistically non-significant decrease of the
      intracellular oxidative activity. No significant differences were observed in
      hemocyte size and complexity, mortality, or phagocytic capacity. Our results
      indicate that in A. trapezia, hemiuroids modulate the immune response by
      increasing the number of circulating hemocytes and decreasing phagocytosis. 

PMID- 23867497
TI  - Effects of pathogenic bacterial challenge after acute sublethal ammonia-N
      exposure on heat shock protein 70 expression in Botia reevesae.
AB  - The objective of this study was to investigate the effects of pathogenic
      bacterial challenge after acute sublethal ammonia-N exposure on heat shock
      protein 70 expression in Botia reevesae. After ammonia-N exposure at a constant
      concentration of 7.21 +/- 0.10 mg L(-1) for 96 h, B. reevesae was challenged with
      Aeromonas hydrophila. Quantitative PCR analysis showed predominant and
      significant expression of HSP70 in liver, gill, skin, spleen and kidney (P <
      0.05), with significantly upregulated expression of the mRNA transcript in these
      tissues after sublethal ammonia-N exposure and A. hydrophila challenge.
      Furthermore, following A. hydrophila challenge after ammonia-N exposure, HSP70
      mRNA expression was significantly upregulated in kidney and gill tissues,
      although its expression levels were significantly lower than those detected
      following A. hydrophila challenge or ammonia-N exposure individually. These
      results indicate that B. reevesae HSP70 is involved in resistance to pathogenic
      bacteria. It is hypothesized that ammonia-N results in the downregulation of
      HSP70 mRNA in immune organs after an A. hydrophila challenge, thus lowering their
      resistance to pathogenic stress.

PMID- 23867498
TI  - Pirfenidone and the inflammasome: getting to the heart of cardiac remodeling.

PMID- 23867499
TI  - MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis.
AB  - MerTK, a receptor tyrosine kinase (RTK) of the TYRO3/AXL/MerTK family, is
      expressed in myeloid lineage cells in which it acts to suppress proinflammatory
      cytokines following ingestion of apoptotic material. Using syngeneic mouse models
      of breast cancer, melanoma, and colon cancer, we found that tumors grew slowly
      and were poorly metastatic in MerTK-/- mice. Transplantation of MerTK-/- bone
      marrow, but not wild-type bone marrow, into lethally irradiated MMTV-PyVmT mice
      (a model of metastatic breast cancer) decreased tumor growth and altered cytokine
      production by tumor CD11b+ cells. Although MerTK expression was not required for
      tumor infiltration by leukocytes, MerTK-/- leukocytes exhibited lower tumor cell
      induced expression of wound healing cytokines, e.g., IL-10 and growth arrest
      specific 6 (GAS6), and enhanced expression of acute inflammatory cytokines, e.g.,
      IL-12 and IL-6. Intratumoral CD8+ T lymphocyte numbers were higher and lymphocyte
      proliferation was increased in tumor-bearing MerTK-/- mice compared with tumor
      bearing wild-type mice. Antibody-mediated CD8+ T lymphocyte depletion restored
      tumor growth in MerTK-/- mice. These data demonstrate that MerTK signaling in
      tumor-associated CD11b+ leukocytes promotes tumor growth by dampening acute
      inflammatory cytokines while inducing wound healing cytokines. These results
      suggest that inhibition of MerTK in the tumor microenvironment may have clinical
      benefit, stimulating antitumor immune responses or enhancing immunotherapeutic
      strategies. 

PMID- 23867500
TI  - Collagen VII plays a dual role in wound healing.
AB  - Although a host of intracellular signals is known to contribute to wound healing,
      the role of the cell microenvironment in tissue repair remains elusive. Here we
      employed 2 different mouse models of genetic skin fragility to assess the role of
      the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1
      secures the attachment of the epidermis to the dermis, and its mutations cause a
      human skin fragility disorder coined recessive dystrophic epidermolysis bullosa
      (RDEB) that is associated with a constant wound burden. We show that COL7A1 is
      instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1
      was required for re-epithelialization through organization of laminin-332 at the
      dermal-epidermal junction. Its loss perturbs laminin-332 organization during
      wound healing, which in turn abrogates strictly polarized expression of integrin
      alpha6beta4 in basal keratinocytes and negatively impacts the laminin
      332/integrin alpha6beta4 signaling axis guiding keratinocyte migration. Second,
      COL7A1 supported dermal fibroblast migration and regulates their cytokine
      production in the granulation tissue. These findings, which were validated in
      human wounds, identify COL7A1 as a critical player in physiological wound healing
      in humans and mice and may facilitate development of therapeutic strategies not
      only for RDEB, but also for other chronic wounds. 

PMID- 23867501
TI  - LXRbeta/estrogen receptor-alpha signaling in lipid rafts preserves endothelial
      integrity.
AB  - Liver X receptors (LXR) are stimulated by cholesterol-derived oxysterols and
      serve as transcription factors to regulate gene expression in response to
      alterations in cholesterol. In the present study, we investigated the role of
      LXRs in vascular endothelial cells (ECs) and discovered that LXRbeta has
      nonnuclear function and stimulates EC migration by activating endothelial NOS
      (eNOS). This process is mediated by estrogen receptor-alpha (ERalpha). LXR
      activation promoted the direct binding of LXRbeta to the ligand-binding domain of
      ERalpha and initiated an extranuclear signaling cascade that requires ERalpha
      Ser118 phosphorylation by PI3K/AKT. Further studies revealed that LXRbeta and
      ERalpha are colocalized and functionally coupled in EC plasma membrane
      caveolae/lipid rafts. In isolated aortic rings, LXR activation of NOS caused
      relaxation, while in mice, LXR activation stimulated carotid artery
      reendothelialization via LXRbeta- and ERalpha-dependent processes. These studies
      demonstrate that LXRbeta has nonnuclear function in EC caveolae/lipid rafts that
      entails crosstalk with ERalpha, which promotes NO production and maintains
      endothelial monolayer integrity in vivo. 

PMID- 23867502
TI  - ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling.
AB  - Nephrotic syndrome (NS) is divided into steroid-sensitive (SSNS) and -resistant
      (SRNS) variants. SRNS causes end-stage kidney disease, which cannot be cured.
      While the disease mechanisms of NS are not well understood, genetic mapping
      studies suggest a multitude of unknown single-gene causes. We combined
      homozygosity mapping with whole-exome resequencing and identified an ARHGDIA
      mutation that causes SRNS. We demonstrated that ARHGDIA is in a complex with RHO
      GTPases and is prominently expressed in podocytes of rat glomeruli. ARHGDIA
      mutations (R120X and G173V) from individuals with SRNS abrogated interaction with
      RHO GTPases and increased active GTP-bound RAC1 and CDC42, but not RHOA,
      indicating that RAC1 and CDC42 are more relevant to the pathogenesis of this SRNS
      variant than RHOA. Moreover, the mutations enhanced migration of cultured human
      podocytes; however, enhanced migration was reversed by treatment with RAC1
      inhibitors. The nephrotic phenotype was recapitulated in arhgdia-deficient
      zebrafish. RAC1 inhibitors were partially effective in ameliorating arhgdia
      associated defects. These findings identify a single-gene cause of NS and reveal
      that RHO GTPase signaling is a pathogenic mediator of SRNS. 

PMID- 23867503
TI  - FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma.
AB  - Oncogenic transcription factors drive many human cancers, yet identifying and
      therapeutically targeting the resulting deregulated pathways has proven
      difficult. Squamous cell carcinoma (SCC) is a common and lethal human cancer, and
      relatively little progress has been made in improving outcomes for SCC due to a
      poor understanding of its underlying molecular pathogenesis. While SCCs typically
      lack somatic oncogene-activating mutations, they exhibit frequent overexpression
      of the p53-related transcription factor p63. We developed an in vivo murine tumor
      model to investigate the function and key transcriptional programs of p63 in SCC.
      Here, we show that established SCCs are exquisitely dependent on p63, as acute
      genetic ablation of p63 in advanced, invasive SCC induced rapid and dramatic
      apoptosis and tumor regression. In vivo genome-wide gene expression analysis
      identified a tumor-survival program involving p63-regulated FGFR2 signaling that
      was activated by ligand emanating from abundant tumor-associated stroma.
      Correspondingly, we demonstrate the therapeutic efficacy of extinguishing this
      signaling axis in endogenous SCCs using the clinical FGFR2 inhibitor AZD4547.
      Collectively, these results reveal an unanticipated role for p63-driven paracrine
      FGFR2 signaling as an addicting pathway in human cancer and suggest a new
      approach for the treatment of SCC. 

PMID- 23867504
TI  - Metastasis-associated PRL-3 induces EGFR activation and addiction in cancer
      cells.
AB  - Metastasis-associated phosphatase of regenerating liver-3 (PRL-3) has pleiotropic
      effects in driving cancer progression, yet the signaling mechanisms of PRL-3 are
      still not fully understood. Here, we provide evidence for PRL-3-induced
      hyperactivation of EGFR and its downstream signaling cascades in multiple human
      cancer cell lines. Mechanistically, PRL-3-induced activation of EGFR was
      attributed primarily to transcriptional downregulation of protein tyrosine
      phosphatase 1B (PTP1B), an inhibitory phosphatase for EGFR. Functionally, PRL-3
      induced hyperactivation of EGFR correlated with increased cell growth,
      promigratory characteristics, and tumorigenicity. Moreover, PRL-3 induced
      cellular addiction to EGFR signaling, as evidenced by the pronounced reversion of
      these oncogenic attributes upon EGFR-specific inhibition. Of clinical
      significance, we verified elevated PRL-3 expression as a predictive marker for
      favorable therapeutic response in a heterogeneous colorectal cancer (CRC) patient
      cohort treated with the clinically approved anti-EGFR antibody cetuximab. The
      identification of PRL-3-driven EGFR hyperactivation and consequential addiction
      to EGFR signaling opens new avenues for inhibiting PRL-3-driven cancer
      progression. We propose that elevated PRL-3 expression is an important clinical
      predictive biomarker for favorable anti-EGFR cancer therapy. 

PMID- 23867505
TI  - Macrophages regulate corpus luteum development during embryo implantation in
      mice.
AB  - Macrophages are prominent in the uterus and ovary at conception. Here we utilize
      the Cd11b-Dtr mouse model of acute macrophage depletion to define the essential
      role of macrophages in early pregnancy. Macrophage depletion after conception
      caused embryo implantation arrest associated with diminished plasma progesterone
      and poor uterine receptivity. Implantation failure was alleviated by
      administration of bone marrow-derived CD11b+F4/80+ monocytes/macrophages. In the
      ovaries of macrophage-depleted mice, corpora lutea were profoundly abnormal, with
      elevated Ptgs2, Hif1a, and other inflammation and apoptosis genes and with
      diminished expression of steroidogenesis genes Star, Cyp11a1, and Hsd3b1.
      Infertility was rescued by exogenous progesterone, which confirmed that uterine
      refractoriness was fully attributable to the underlying luteal defect. In
      normally developing corpora lutea, macrophages were intimately juxtaposed with
      endothelial cells and expressed the proangiogenic marker TIE2. After macrophage
      depletion, substantial disruption of the luteal microvascular network occurred
      and was associated with altered ovarian expression of genes that encode vascular
      endothelial growth factors. These data indicate a critical role for macrophages
      in supporting the extensive vascular network required for corpus luteum integrity
      and production of progesterone essential for establishing pregnancy. Our findings
      raise the prospect that disruption of macrophage-endothelial cell interactions
      underpinning corpus luteum development contributes to infertility in women in
      whom luteal insufficiency is implicated. 

PMID- 23867506
TI  - Palliative treatment for in-transit cutaneous metastases of Merkel cell carcinoma
      using surface-mold computer-optimized high-dose-rate brachytherapy.
AB  - PURPOSE: The objective of this study was to evaluate the palliative treatment
      benefit of surface-mold computer-optimized high-dose-rate brachytherapy (SMBT)
      for in-transit cutaneous metastases of Merkel cell carcinoma (MCC). METHODS: Ten
      patients with in-transit cutaneous MCC metastases were treated with SMBT at the
      Dana-Farber/Brigham & Women's Cancer Center between 2006 and 2012. RESULTS: The
      median age at diagnosis was 76 years (range, 63-87 years). Seven patients had in
      transit metastases on the lower extremities (70%), 2 patients on the head and
      neck (20%), and 1 patient on an upper extremity (10%). A total of 152 metastatic
      MCC lesions were treated with SMBT. All SMBT-treated lesions resolved clinically
      within a few weeks of therapy. The median follow-up was 34 months (range, 22-85
      months). Two of 152 treated lesions recurred during the study period for a local
      control rate of 99%. Eight patients (80%) developed additional in-transit
      metastases outside the original SMBT fields. Five of these 8 patients underwent
      additional SMBT. At study conclusion, 3 patients (30%) are alive without disease,
      3 patients (30%) are alive with disease, and 4 patients (40%) died of MCC.
      DISCUSSION: Surface-mold computer-optimized high-dose-rate brachytherapy offers
      effective and durable palliation for cutaneous metastases of MCC, although it
      does not appear to alter disease course.

PMID- 23867507
TI  - Role of radiotherapy in adrenocortical carcinoma.
AB  - PURPOSE: Adrenocortical carcinoma (ACC) is a rare and highly malignant tumor
      usually diagnosed in an advanced stage. Radiation therapy has been a poorly
      studied and underutilized therapeutic option. METHODS: This retrospective
      analysis reviewed treatment courses for 14 patients with pathologically confirmed
      ACC treated between 1997 and 2012. Two patients were treated adjuvantly following
      surgery, and 12 were treated with palliative intent. Patients presented with
      stage II (n = 4), stage III (n = 7), and stage IV (n = 3) disease. Patients had a
      mean age of 51.5 years. Ten patients received chemotherapy before radiotherapy
      (RT), and 12 patients received surgery before RT, before receiving radiation at a
      mean of 17.8 months after diagnosis. RESULTS: In total, 20 sites were treated, 2
      of which were in an adjuvant setting, and 18 of which were for palliative
      indications in 12 patients as follows: (1) pain/neuropathy (n = 10), (2)
      prophylactic treatment of asymptomatic recurrences (n = 3), and (3) prevention of
      imminent metastatic complications (n = 2), hemoptysis (n = 1), severe mass effect
      (n = 1), and brain metastasis (n = 1). Sites were treated to a median dose of
      36.3 Gy (range, 17.5-60 Gy) in a median of 2.5 Gy/fraction (range, 1.8-4 Gy). At
      a mean follow-up of 22.0 months for the 2 patients given adjuvant RT, 1 patient
      did not have a local recurrence during a 14.3-month period of follow-up, and the
      other had a local recurrence 14.5 months after RT. At a mean follow-up of 11.3
      months for the 12 patients receiving palliative RT, 10 patients had either a
      clinical or radiographic response. Of the courses of palliative RT that had
      adequate radiographic follow-up, 4 treatments (27%) resulted in a partial
      response. Eleven treatments (73%) that were able to be evaluated resulted in
      clinical improvement. Acute Radiation Therapy Oncology Group/European
      Organization for Research and Treatment of Cancer toxicities observed in 7
      patients included 3 grade 1, 4 grade 2, and 1 grade 3. No patient had acute
      toxicity of grade 4 or greater or any Radiation Therapy Oncology Group/European
      Organization for Research and Treatment of Cancer late toxicity of grade 1 or
      greater. DISCUSSION: This report is one of the largest to date examining the role
      of modern radiation techniques in the management of ACC. We conclude that
      radiation can be effective in the management of metastatic ACC, palliating local
      symptoms, and preventing complications from large metastases. Radiation should be
      considered as an option in multimodality management of ACC patients.

PMID- 23867508
TI  - Radiotherapy for rare tumors.

PMID- 23867509
TI  - From the guest editor: renal cell carcinoma: the next decade of development.

PMID- 23867510
TI  - Novel approaches targeting the vascular endothelial growth factor axis in renal
      cell carcinoma.
AB  - In recent years, functional characterization of the von Hippel-Lindau tumor
      suppressor, hypoxia-induced factors, and one of their key downstream effectors,
      the vascular endothelial growth factor (VEGF), has revolutionized treatment of
      advanced renal cell carcinoma. Therapeutic strategies targeting the ligand itself
      (VEGF-A) or its receptor (VEGFR2) have proven successful. However, complete
      remissions are rare, and with time patients invariably suffer disease
      progression. It is understood that this is due to incomplete suppression of VEGF
      signaling and/or adaptive up-regulation of non-VEGF-dependent tumor-promoting
      stimuli. In this article, we review novel VEGF-directed agents that are being
      developed to address the shortcomings of current targeted drugs for the treatment
      of advanced renal cell carcinoma. Building on our current understanding of
      molecular mechanisms behind resistance, examples include next-generation
      multitarget tyrosine kinase inhibitors, biologics, and other compounds. 

PMID- 23867511
TI  - Angiopoietins and non-vascular endothelial growth factor antiangiogenic targets
      in advanced renal cell carcinoma.
AB  - The treatment of metastatic renal cell carcinoma has evolved from an era
      dominated by immune modulation to an era of antiangiogenesis agents. Blockade of
      vascular endothelial growth factor-mediated pathways and mammalian target of
      rapamycin pathways has accounted for most of these gains. Although these agents
      have offered dramatic improvements in survival for kidney cancer patients,
      resistance inevitably occurs, and new classes of agents are needed to continue to
      improve outcomes in this setting. We discuss several alternative pathways of
      angiogenesis, which are being investigated as targets to overcome treatment
      resistance, including angiopoietin family proteins, fibroblast growth factor,
      platelet-derived growth factor, and vascular disrupting agents. 

PMID- 23867512
TI  - Novel targeting of phosphatidylinositol 3-kinase and mammalian target of
      rapamycin in renal cell carcinoma.
AB  - Allosteric inhibitors of the kinase mammalian target of rapamycin (mTOR) have
      demonstrated significant clinical activity in patients with advanced renal cell
      carcinoma (RCC). Unfortunately, substantial clinical responses to these
      rapalogues are seen only in a subset of patients with advanced RCC. Preclinical
      studies have identified multiple theoretical shortcomings of the rapalogues, and
      numerous novel agents directed against the phosphatidylinositol 3-kinase/Akt/mTOR
      pathway, which address many of these shortcomings, are in active clinical
      development. In this review, we discuss the preclinical and clinical experience
      with the rapalogues in RCC, potential mechanisms of resistance to the rapalogues,
      and the progress in the clinical development of novel agents directed against the
      phosphatidylinositol 3-kinase/Akt/mTOR pathway. 

PMID- 23867513
TI  - Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell
      carcinoma.
AB  - The product of a proto-oncogene, the c-Met protein is a transmembrane receptor
      tyrosine kinase. Its only known ligand, hepatocyte growth factor/scatter factor,
      regulates cell growth, motility, migration, invasion, proliferation, and
      angiogenesis. Dysregulation of c-Met and hepatocyte growth factor have been
      observed in both clear cell and non-clear cell renal cell carcinomas (RCCs),
      although only papillary RCCs harbor activating mutations in the MET gene. In
      clear cell RCC, there is evidence of a direct link between loss of von Hippel
      Lindau and up-regulation of c-Met. As in other cancers, high expression of c-Met
      correlates with worse outcomes in RCC. In vitro and in vivo preclinical RCC
      models demonstrate cancer control with small molecule and antibodies against c
      Met. Given these findings, the c-Met pathway is a logical therapeutic target in
      RCC, and several agents are in clinical testing with early signs of efficacy. 

PMID- 23867516
TI  - Inhibiting autophagy: a novel approach for the treatment of renal cell carcinoma.
AB  - The common clear cell subtype of renal cell carcinoma is associated with
      hereditary or acquired loss of function of the von Hippel-Lindau tumor
      suppressor, a key component in oxygen sensing, perpetuating a stressed state.
      Autophagy is primarily a highly conserved, catabolic process by which stressed
      cells shuttle damaged or effete organelles and proteins into autophagosomes for
      sequestration and digestion after fusion with lysosomes. Autophagy is directed by
      autophagy-related genes and is divided into 4 discrete steps: initiation,
      nucleation, maturation, and degradation. During early tumorigenesis, apoptosis is
      enhanced and autophagy is suppressed, allowing accumulation of mutations and
      emergence of genomic instability. Late, an "autophagic switch" occurs, promoting
      survival and limiting apoptosis. Compounds such as chloroquine and
      hydroxychloroquine that prevent acidification of the lysosomal compartment are
      the sole clinically available inhibitors of autophagy. Currently, there are more
      than 30 trials examining combinations of hydroxychloroquine with anticancer
      agents. The intricate effects of autophagy on the immune response complicate
      manipulation of autophagy as part of the antitumor strategy. Further
      understanding of basic mechanisms of renal cell carcinoma pathogenesis and of
      autophagy will enable development of the next generation of pharmacologic
      modulators of autophagy. 

PMID- 23867514
TI  - PBRM1 and BAP1 as novel targets for renal cell carcinoma.
AB  - Technological advances in genome sequencing have led to the identification of
      novel driver genes mutated in renal cancer. Hitherto, 1 gene was known to be
      frequently mutated in renal cell carcinoma of clear cell type (ccRCC), the von
      Hippel-Lindau (VHL) gene. VHL was identified by positional cloning as the gene
      responsible for a familial syndrome with renal cancer predisposition, von Hippel
      Lindau. Subsequently, VHL was found to be inactivated in approximately 90% of
      sporadic ccRCC. The discovery of VHL, together with the elucidation of its
      function, transformed the treatment of ccRCC leading to the introduction of 5 new
      drugs into the clinic. However, no other familial ccRCC predisposing genes are
      frequently mutated in sporadic ccRCC. With the development of massively parallel
      sequencing, a plethora of somatically mutated genes has been identified. Most
      genes are mutated at low frequencies, but 3 genes are mutated in more than 10% of
      ccRCC, PBRM1 (mutated in ~50%), BAP1 (~15%), and SETD2 (~15%). Like VHL, all 3
      genes are 2-hit tumor suppressor genes. Furthermore, these 3 genes are within a
      50-Mb region on the short arm of chromosome 3p that encompasses VHL and is
      deleted in ~90% of ccRCC. We discovered that PBRM1 mutations tend to
      anticorrelate with BAP1 mutations in ccRCC and that PBRM1- and BAP1-mutated
      tumors exhibit different biology and are associated with markedly different
      outcomes. This established the foundation for the first molecular genetic
      classification of sporadic ccRCC. Herein, I review the evidence that implicated
      PBRM1 and BAP1 as renal cancer driver genes, provide an update on the function of
      the gene products, and speculate on how mutations in these genes may be exploited
      therapeutically.

PMID- 23867515
TI  - Histone deacetylase inhibitors and epigenetic modifications as a novel strategy
      in renal cell carcinoma.
AB  - Recent investigations of renal cell carcinoma (RCC) have revealed several
      epigenetic modifications, as well as alterations in the genes and enzymes that
      regulate these changes. Preclinical models have revealed that histone gene
      modifiers and epigenetic alterations may play a critical role in RCC
      tumorigenesis. Specific changes in DNA methylation and mutations of histone
      modifiers have been identified and may be associated with an aggressive
      phenotype. In addition, the potential of reversing the effects of these enzymes
      and hence reversing the cellular epigenetic landscape to a "normal phenotype"
      have led to an increasing interest in developing targeted chromatin remodeling
      agents. However, the translation of the understanding of these changes to the
      clinic for the treatment of RCC has posed significant challenges, partly due to
      tumor heterogeneity. This review describes the aberrant histone and DNA
      alterations recently reported in RCC and highlights the potential targeted
      chromatin remodeling therapies in the management of this disease. 

PMID- 23867517
TI  - Immune checkpoint inhibitors as novel targets for renal cell carcinoma
      therapeutics.
AB  - Monoclonal antibodies targeting programmed death 1, programmed death ligand 1,
      and cytotoxic T-lymphocyte antigen 4 pathways are currently in development for
      metastatic renal cell carcinoma. By inhibiting these immune regulatory pathways,
      these agents improve the immune response to cancer with the goal of creating
      durable responses. Although still early in development, several agents have been
      studied in phases I and II setting for metastatic renal cell carcinoma, with 1
      drug in phase III testing (nivolumab). The unique toxicity profile of this class
      of therapy presents challenges to the treating clinician. Ongoing clinical trials
      hope to define patients who will benefit based on predictive biomarkers. Immune
      checkpoint inhibitors may play a key role in the future of management of solid
      tumors including kidney cancer. 

PMID- 23867519
TI  - A new age for vaccine therapy in renal cell carcinoma.
AB  - Over the past several years, the dominant paradigm in drug development for
      metastatic renal cell carcinoma (mRCC) has been to more selectively and potently
      target moieties such as the vascular endothelial growth factor receptor. The
      effectiveness of this strategy appears to be nearing a plateau, however,
      underscoring the need for novel approaches. Vaccine-based therapies represent one
      such approach. Several distinct vaccines are currently being examined in mRCC,
      each using a distinct mechanism of action. For instance, the autologous dendritic
      cell vaccine AGS-003 uses patient-specific antigens derived from primary tumor
      tissue. In contrast, the poxvirus vaccine TG4010 produces an antigenic response
      to MUC1, a cell surface glycoprotein that reduces cell-cell interactions and
      thereby precludes contact inhibition. Other vaccines elicit a response to a
      broader spectrum of antigens-for instance, the vaccine IMA901 is based on 9 tumor
      associated peptides identified from a novel biotechnology platform combining mass
      spectroscopy, microarray analysis of RNA expression, and immunogenicity assays.
      Herein, the current status of vaccine-based therapies for mRCC is described in
      detail. Furthermore, challenges to clinical implementation (eg, cost, optimal
      pairing with targeted agents, appropriate sequencing) are presented. 

PMID- 23867520
TI  - Evidence-based recommendations for optimal dietary protein intake in older
      people: a position paper from the PROT-AGE Study Group.
AB  - New evidence shows that older adults need more dietary protein than do younger
      adults to support good health, promote recovery from illness, and maintain
      functionality. Older people need to make up for age-related changes in protein
      metabolism, such as high splanchnic extraction and declining anabolic responses
      to ingested protein. They also need more protein to offset inflammatory and
      catabolic conditions associated with chronic and acute diseases that occur
      commonly with aging. With the goal of developing updated, evidence-based
      recommendations for optimal protein intake by older people, the European Union
      Geriatric Medicine Society (EUGMS), in cooperation with other scientific
      organizations, appointed an international study group to review dietary protein
      needs with aging (PROT-AGE Study Group). To help older people (>65 years)
      maintain and regain lean body mass and function, the PROT-AGE study group
      recommends average daily intake at least in the range of 1.0 to 1.2 g protein per
      kilogram of body weight per day. Both endurance- and resistance-type exercises
      are recommended at individualized levels that are safe and tolerated, and higher
      protein intake (ie, >= 1.2 g/kg body weight/d) is advised for those who are
      exercising and otherwise active. Most older adults who have acute or chronic
      diseases need even more dietary protein (ie, 1.2-1.5 g/kg body weight/d). Older
      people with severe kidney disease (ie, estimated GFR <30 mL/min/1.73 m(2)), but
      who are not on dialysis, are an exception to this rule; these individuals may
      need to limit protein intake. Protein quality, timing of ingestion, and intake of
      other nutritional supplements may be relevant, but evidence is not yet sufficient
      to support specific recommendations. Older people are vulnerable to losses in
      physical function capacity, and such losses predict loss of independence, falls,
      and even mortality. Thus, future studies aimed at pinpointing optimal protein
      intake in specific populations of older people need to include measures of
      physical function.

PMID- 23867518
TI  - Modification of the tumor microenvironment as a novel target of renal cell
      carcinoma therapeutics.
AB  - To move forward with immunotherapy, it is important to understand how the tumor
      microenvironment generates systemic immunosuppression in patients with renal cell
      carcinoma (RCC) as well as in patients with other types of solid tumors. Even
      though antigen discovery in RCC has lagged behind melanoma, recent clinical
      trials have finally authenticated that RCC is susceptible to vaccine-based
      therapy. Furthermore, judicious coadministration of cytokines and chemotherapy
      can potentiate therapeutic responses to vaccine in RCC and prolong survival, as
      has already proved possible for melanoma. Although high-dose interleukin 2
      immunotherapy has been superseded as first-line therapy for RCC by promiscuous
      receptor tyrosine kinase inhibitors (rTKIs) such as sunitinib, sunitinib itself
      is a potent immunoadjunct in animal tumor models. A reasonable therapeutic goal
      is to unite antiangiogenic strategies with immunotherapy as first-line therapy
      for RCC. This strategy is equally appropriate for testing in all solid tumors in
      which the microenvironment generates immunosuppression. A common element of RCC
      and pancreatic, colon, breast, and other solid tumors is large numbers of
      circulating myeloid-derived suppressor cells (MDSCs), and because MDSCs elicit
      regulatory T cells rather than vice versa, gaining control over MDSCs is an
      important initial step in any immunotherapy. Although rTKIs like sunitinib have a
      remarkable capacity to deplete MDSCs and restore normal T-cell function in
      peripheral body compartments such as the bloodstream and the spleen, such rTKIs
      are effective only against MDSCs, which are engaged in phospho-STAT3-dependent
      programming (pSTAT3+). Unfortunately, rTKI-resistant pSTAT3- MDSCs are especially
      apt to arise within the tumor microenvironment itself, necessitating strategies
      that do not rely exclusively on STAT3 disruption. The most utilitarian strategy
      to gain control of both pSTAT3+ and pSTAT3- MDSCs may be to exploit the natural
      differentiation pathway, which permits MDSCs to mature into tumoricidal
      macrophages (TM1) via such stimuli as Toll-like receptor agonists, interferon
      gamma, and CD40 ligation. Overall, this review highlights the mechanisms of
      immune suppression used by the different regulatory cell types operative in RCC
      as well as other tumors. It also describes the different therapeutic strategies
      to overcome the suppressive nature of the tumor microenvironment. 

PMID- 23867521
TI  - The carotenoid lycopene protects rats against DNA damage induced by Ochratoxin A.
AB  - Ochratoxin A (OTA), one of the most prevalent mycotoxins in the world, has
      nephrotoxic and hepatotoxic properties. Lycopene is an important carotenoid and
      has a high singlet-oxygen and free-radical scavenging capacity. This study was
      designed to investigate the possible protective effects of lycopene against the
      genotoxicity of OTA in rat tissues using the alkaline comet assay. Male Sprague
      Dawley rats were used in the experiments. OTA (0.5 mg/kg b.w./day) was
      administered by gavage for 14 days, whereas lycopene was applied on the last 7
      days or for 14 days of the feeding period, with OTA treatment. OTA caused marked
      increases in tail length, tail moment, and tail intensity vs. control both in the
      kidney and liver cells, but not in the lymphocytes. Lycopene administration alone
      for 7 and 14 days did not provide any significant change in DNA damage of the
      lymphocytes, renal and hepatic cells vs. controls. However, lycopene for both 7
      and 14 days, with OTA exposure in renal and hepatic cells, supplied significant
      decreases in tail length, tail moment, and tail intensity vs. OTA-exposed rats.
      The effect of 14 days supplementation seemed to be more protective, particularly
      against hepatic cells. These results suggest that lycopene may protect hepatic
      and renal tissue from OTA-induced DNA damage. 

PMID- 23867523
TI  - Ischemic preconditioning results in an ATP-dependent inhibition of cytochrome C
      oxidase.
AB  - PURPOSE: This study addresses the effect of short myocardial ischemia on
      inhibitory effect of ATP for mitochondrial cytochrome c oxidase (CytOx) activity
      in myocardium and subsequent hemodynamic alterations. The activity of CytOx is
      inhibited by ATP (primary substrate control). This additional mechanism was
      proposed to be switched off at higher mitochondrial membrane potential values in
      case of stress. The ATP-dependent allosteric enzyme inhibition (second
      respiratory control) is suggested to reduce the formation of reactive oxygen
      species and thus is pivotal for cytoprotection. This report addresses the
      possible involvement of this mechanism in case of myocardial preconditioning.
      METHODS: Rat hearts were perfused in a Langendorff system (n = 5 each group). The
      first two groups underwent short recurrent ischemic periods (three times 5 min)
      and subsequent high or low reperfusion for 40 min. Besides four control groups,
      hearts were exposed to an ischemia of 15 min and high flow reperfused for 30 min,
      in addition. Hemodynamic data were evaluated in parallel. Mitochondria were
      separated for the polarographic respiration measurements in the presence of ADP
      or ATP, respectively. Phosphorylation patterns of the CytOx subunits were studied
      by immunoblotting with P-Ser, P-Thr, and P-Tyr antibodies. RESULTS: Short
      recurrent episodes of ischemia result in an ATP-dependent inhibition of CytOx.
      Electrophoretic analysis and blotting techniques reveal different phosphorylation
      patterns of the enzyme. Frequent short-lasting ischemic impacts and subsequent
      increased coronary flow seem to be essential for this effect. CONCLUSION: The
      procedure of preconditioning is likely to be dependent on the mechanism of ATP
      dependent inhibition of CytOx activity.

PMID- 23867524
TI  - Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved
      pharmacokinetics and lowered plasma phenylalanine levels in normal mice.
AB  - Enzyme replacement therapy is often hampered by the rapid clearance and
      degradation of the administered enzyme, limiting its efficacy and requiring
      frequent dosing. Encapsulation of therapeutic molecules into red blood cells
      (RBCs) is a clinically proven approach to improve the pharmacokinetics and
      efficacy of biologics and small molecule drugs. Here we evaluated the ability of
      RBCs encapsulated with phenylalanine hydroxylase (PAH) to metabolize
      phenylalanine (Phe) from the blood and confer sustained enzymatic activity in the
      circulation. Significant quantities of PAH were successfully encapsulated within
      murine RBCs (PAH-RBCs) with minimal loss of endogenous hemoglobin. While
      intravenously administered free PAH enzyme was rapidly eliminated from the blood
      within a few hours, PAH-RBCs persisted in the circulation for at least 10days. A
      single injection of PAH-RBCs was able to decrease Phe levels by nearly 80% in
      normal mice. These results demonstrate the ability of enzyme-loaded RBCs to
      metabolize circulating amino acids and highlight the potential to treat disorders
      of amino acid metabolism. 

PMID- 23867525
TI  - Response to Stove and colleagues concerning newborn screening of succinic
      semialdehyde dehydrogenase (SSADH) deficiency in dried blood spots.

PMID- 23867526
TI  - Genomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice.
AB  - We used a genome-wide single nucleotide polymorphism (SNP) approach to
      characterize the genomic structures of four representative C57BL/6 (B6) congenic
      mutant mouse lines to include the A) long-chain acyl-CoA dehydrogenase (Acadl),
      B) melanocortin 3 receptor (Mc3r), C) endothelial nitric oxide synthase (Nos3),
      and D) a replacement of mouse apolipoprotein E (Apoe) by human apolipoprotein E-2
      (APOE2). We wanted to evaluate the size and flanking genes of the 129 strain
      origin mutant allele intervals on the B6 background. Additionally, we wanted to
      evaluate genetic drift among not only the four mutant lines and their respective
      B6 origin substrains, but also the drift between two commonly used B6 lines
      obtained from Jackson Laboratory and Taconic. Overall, we found a range of 129
      origin interval sizes in the congenic mutant lines analyzed that ranged from a
      ~2.8 kb human sequence for APOE2 embedded in a 129S6 interval to the largest
      being a ~16 Mb fragment containing the targeted Nos3 (eNos) gene. Given the range
      of 129 strain interval sizes, we found 129 strain flanking genes via annotation
      in genome data bases ranging from one gene both upstream and downstream of the
      APOE2 allele to seven genes-upstream and five genes-downstream at the Nos3 locus.
      Furthermore, we found fourteen SNP differences between the Jackson Laboratory and
      Taconic B6 mice. These genetic differences were associated with marked adiposity
      differences between the two B6 substrains. This study demonstrates both the
      fidelity and the caveats of using congenic gene targeted mouse models and
      recognizing the importance of selecting the appropriately matched wild-type
      control mouse line.

PMID- 23867527
TI  - Environmentally friendly pretreatment of plant biomass by planetary and attrition
      milling.
AB  - This study evaluated the use of planetary and attrition milling as pretreatment
      processes for lignocellulosic biomass using rice straw. Planetary milling reduced
      the rice straw crystallinity from 0.48 to 0.11. Since the samples could be milled
      and enzymatically treated using the same media, loss of the biomass due to
      washing was effectively eliminated. In contrast, conventional sodium hydroxide
      and soaking in aqueous ammonia (SAA) processes showed a loss of 34.2% and 14.8%,
      respectively. Furthermore, milling produced significantly lower concentrations of
      soluble phenolics than the alkali treatments. Using a bioluminescent bioreporter
      strain that is sensitive to these phenolics, neither of the milled samples
      elicited a response while the sodium hydroxide and SAA samples led to a 25.8 and
      4.7 -fold induction, respectively. Although planetary milling produced more
      reducing sugars than attrition milling before saccharification, both had similar
      monosaccharide yields, i.e., 0.38 and 0.34 g/g-biomass, respectively, when 40 g/l
      rice straw was treated.

PMID- 23867528
TI  - Performances of anaerobic co-digestion of fruit & vegetable waste (FVW) and food
      waste (FW): single-phase vs. two-phase.
AB  - The co-digestion of fruit & vegetable waste (FVW) and food waste (FW) was
      performed at various organic loading ratios (OLRs) in single-phase and two-phase
      system, respectively. The results showed that the ethanol-type fermentation
      dominated in both digestion processes when OLR was at low levels (<2.0 g(VS) L(
      1) d(-1)). The propionic acid was rapidly accumulated as OLR was increased to
      higher levels (>2.0 g(VS) L(-1) d(-1)), which could cause unstable anaerobic
      digestion. Single-phase digestion was better than two-phase digestion in term of
      4.1% increase in CH4 production at lower OLRs (<2.0 g(VS) L(-1) d(-1)). However,
      at higher level of OLR (>=2.0 g(VS) L(-1) d(-1)), two-phase digestion achieved
      higher CH4 production of 0.351-0.455 L(g VS)(-1) d(-1), which were 7.0-15.8% more
      than that of single-phase. Additionally, two-phase digestion presented more
      stable operation, and higher OLR treatment capacity. Furthermore, comparison of
      these two systems with bioenergy recovery revealed that two-phase system overall
      presented higher bioenergy yield than single-phase.

PMID- 23867529
TI  - Nutrient removal performance and microbial community structure in an EBPR system
      under the limited filamentous bulking state.
AB  - Limited filamentous bulking (LFB) was proposed to be a new method for saving
      energy and improving effluent quality. In order to validate the stability of LFB
      in enhanced biological phosphorus removal (EBPR) systems, the LFB was further
      achieved in a lab-scale EBPR. Nutrient removal performance and microbial
      community structure including dominant filaments and polyphosphate-accumulating
      organisms (PAOs) were investigated. Results showed that the enriched PAOs could
      alleviate the negative effect of low dissolved oxygen concentration on sludge
      settleability, making the LFB be more easily achieved and maintained in the EBPR
      for long-term operation. Sludge volume index was kept between 150-200 mL/g during
      the LFB period. Larger floc size (>=400 MUm) was commonly observed under the LFB
      state, which significantly enhanced the simultaneous nitrification and
      denitrification (SND) efficiency. An average SND efficiency of 36% was observed
      in the EBPR system when the LFB occurred.

PMID- 23867530
TI  - Aerobic biodegradation process of petroleum and pathway of main compounds in
      water flooding well of Dagang oil field.
AB  - Aerobic biodegradation of crude oil and its pathways were investigated via in
      vitro culture and GC-MS analysis in water flooding wells of Dagang oil field. The
      in vitro aerobic culture lasted 90 days when 99.0% of n-alkanes and 43.03-99.9%
      of PAHs were degraded and the biomarkers and their ratios were changed. The
      spectra of components in the residual oil showed the similar biodegradation
      between aerobic process of 90 days and degradation in reservoir which may last
      for some millions years, and the potential of serious aerobic biodegradation of
      petroleum in reservoir. 24 Metabolites compounds were separated and identified
      from aerobic culture, including fatty acid, naphthenic acid, aromatic carboxylic
      acid, unsaturated acid, alcohols, ketones and aldehydes. The pathways of alkanes
      and aromatics were proposed, which suggests that oxidation of hydrocarbon to
      organic acid is an important process in the aerobic biodegradation of petroleum.

PMID- 23867531
TI  - Decentralized application of anaerobic digesters in small poultry farms:
      performance analysis of high rate self mixed anaerobic digester and conventional
      fixed dome anaerobic digester.
AB  - Biomethanation of poultry litter was studied in conventional fixed dome anaerobic
      digester (CFDAD) and high rate self mixed anaerobic digester (SMAD) for possible
      decentralized application in poultry farms generating litter in the range of 500
      kg/day. The performance of CFDAD and SMAD was compared. The study revealed that
      optimized hydraulic residence time (HRT), volatile solids (VS) loading rate, VS
      reduction, methane yield was 24 days, 4.0 kg VS/m(3)/day, 64%, 0.15 m(3)/(kg VS
      fed) and 40 days, 2.15 kg/m(3)/day, 42%, 0.083 m(3)/(kg VS fed) for SMAD and
      CFDAD, respectively. Better results with SMAD could be attributed to specific
      design features and intermittent mixing of the digester contents due to self
      mixing mechanism. Preliminary cost estimates revealed that installation of SMAD
      would be remunerative for the farmer in terms of biogas and bio-manure.

PMID- 23867532
TI  - Dynamic effect of total solid content, low substrate/inoculum ratio and particle
      size on solid-state anaerobic digestion.
AB  - Among all the process parameters of solid-state anaerobic digestion (SS-AD),
      total solid content (TS), inoculation (S/X ratio) and size of the organic solid
      particles can be optimized to improve methane yield and process stability. To
      evaluate the effects of each parameter and their interactions on methane
      production, a three level Box-Behnken experimental design was implemented in SS
      AD batch tests degrading wheat straw by adjusting: TS content from 15% to 25%,
      S/X ratio (in volatile solids) between 28 and 47 and particle size with a mean
      diameter ranging from 0.1 to 1.4mm. A dynamic analysis of the methane production
      indicates that the S/X ratio has only an effect during the start-up phase of the
      SS-AD. During the growing phase, TS content becomes the main parameter governing
      the methane production and its strong interaction with the particle size suggests
      the important role of water compartmentation on SS-AD. 

PMID- 23867533
TI  - Benefit of sodium hydroxide pretreatment of ensiled sorghum forage on the
      anaerobic reactor stability and methane production.
AB  - The assessment of the pretreatment effect on the anaerobic digestion process is
      generally based on the results of batch tests, which may fail in truly predicting
      full-scale anaerobic reactors performance. Therefore, in this study, the effect
      of alkaline pretreatment on the anaerobic digestion of ensiled sorghum forage was
      evaluated by comparing the results of two semi-continuous CSTR (Continuously
      Stirred Tank Reactor) anaerobic reactors. Results showed that an alkaline
      pretreatment step, prior to the anaerobic digestion of ensiled sorghum forage,
      can have a beneficial effect both in enhancing methane production (an increase of
      25% on methane production was observed, if compared to that of untreated sorghum)
      and in giving more stability to the anaerobic digestion process. 

PMID- 23867534
TI  - Biohydrogen production from microalgal biomass: energy requirement, CO2 emissions
      and scale-up scenarios.
AB  - This paper presents a life cycle inventory of biohydrogen production by
      Clostridium butyricum through the fermentation of the whole Scenedesmus obliquus
      biomass. The main purpose of this work was to determine the energy consumption
      and CO2 emissions during the production of hydrogen. This was accomplished
      through the fermentation of the microalgal biomass cultivated in an outdoor
      raceway pond and the preparation of the inoculum and culture media. The scale-up
      scenarios are discussed aiming for a potential application to a fuel cell hybrid
      taxi fleet. The H2 yield obtained was 7.3 g H2/kg of S. obliquus dried biomass.
      The results show that the production of biohydrogen required 71-100 MJ/MJ(H2) and
      emitted about 5-6 kg CO2/MJ(H2). Other studies and production technologies were
      taken into account to discuss an eventual process scale-up. Increased production
      rates of microalgal biomass and biohydrogen are necessary for bioH2 to become
      competitive with conventional production pathways.

PMID- 23867535
TI  - Performance of microbial fuel cell coupled constructed wetland system for
      decolorization of azo dye and bioelectricity generation.
AB  - A microbial fuel cell coupled constructed wetland (planted with Ipomoea aquatica)
      system (planted CW-MFC) was used for azo dye decolorization. Electricity was
      simultaneously produced during the co-metabolism process of glucose and azo dye.
      A non-planted and an open-circuit system were established as reference to study
      the roles of plants and electrodes in azo dye decolorization and electricity
      production processes, respectively. The results indicated that plants grown in
      cathode enhanced the cathode potential and slightly promoted dye decolorization
      efficiency. The electrodes promoted the dye decolorization efficiency in the
      anode. The planted CW-MFC system achieved the highest decolorization rate of
      about 91.24% and a voltage output of about 610 mV. The connection of external
      circuit promoted the growth of electrogenic bacteria Geobacter sulfurreducens and
      Beta Proteobacteria, and inhibited the growth of Archaea in anode.

PMID- 23867536
TI  - Co-production of furfural and acetic acid from corncob using ZnCl2 through fast
      pyrolysis in a fluidized bed reactor.
AB  - Corncob was pyrolyzed using ZnCl2 in a pyrolysis plant equipped with a fluidized
      bed reactor to co-produce furfural and acetic acid. The effects of reaction
      conditions, the ZnCl2 content and contacting method of ZnCl2 with corncob on the
      yields of furfural and acetic acid were investigated. The pyrolysis was performed
      within the temperature range between 310 and 410 degrees C, and the bio-oil yield
      were 30-60 wt% of the product. The furfural yield increased up to 8.2 wt%. The
      acetic acid yield was maximized with a value of 13.1 wt%. A lower feed rate in
      the presence of ZnCl2 was advantageous for the production of acetic acid. The
      fast pyrolysis of a smaller corncob sample mechanically mixed with 20 wt% of
      ZnCl2 gave rise to a distinct increase in furfural. A high selectivity for
      furfural and acetic acid in bio-oil would make the pyrolysis of corncob with
      ZnCl2 very economically attractive.

PMID- 23867537
TI  - Wheat bran biorefinery--a detailed investigation on hydrothermal and enzymatic
      treatment.
AB  - Due to the enormous quantities arising in the milling industry and its specific
      properties, wheat bran can be considered as a feedstock for future biorefineries.
      In the present work, a detailed investigation was carried out on the hydrothermal
      (140-200 degrees C) and enzymatic treatment of wheat bran. After hydrothermal
      pretreatment and a subsequent enzymatic hydrolysis a glucose yield of 65% and 90%
      was achieved, respectively. Interestingly, the hemicelluloses could be
      disintegrated to monomers only to approx. 50%. About 70% of the proteins were
      dissolved, however, practically no free amino acids were obtained under given
      conditions. Severe treatment conditions induce elevated losses of some amino
      acids. Minerals could be extracted almost completely. To disintegrate fat into
      glycerol and fatty acids severe process conditions were necessary. The formation
      of undesired by-products such as furfural or hydroxymethylfurfural starts at
      approx. 180 degrees C. 

PMID- 23867538
TI  - Recycling cellulase from enzymatic hydrolyzate of acid treated wheat straw by
      electroultrafiltration.
AB  - This work explores the feasibility of recycling cellulase by
      electroultrafiltration (EUF), an ultrafiltration process enhanced by an electric
      field, to reduce the cost of enzymatic transformation of cellulose. The effect of
      electric field under different operating conditions (buffer concentration, acid
      treated wheat straw concentration, current and temperature) on flux during EUF
      was examined. The results showed that EUF was effective to reduce concentration
      polarization (CP) and enhance filtration flux in recycling cellulase. The flux
      improvement by the electric field could be strengthened at low buffer
      concentration (5 mM) and relatively low temperature (room temperature) and high
      current (150 mA). The flux for 2% (substrate concentration, w/v) lignocellulosic
      hydrolyzate increased by a factor of 4.4 at 836 V/m and room temperature,
      compared to that without electric field. This work shows that under appropriate
      operating conditions EUF can efficiently recycle cellulase from lignocellulosic
      hydrolyzate and thus substantially reduce hydrolysis cost.

PMID- 23867539
TI  - Stroke volume optimization after anaesthetic induction: An open randomized
      controlled trial comparing 0.9% NaCl versus 6% hydroxyethyl starch 130/0.4.
AB  - OBJECTIVE: Postinduction hypotension during general anaesthesia could be
      corrected by a rapid cardiac preload optimization by fluid infusion. The type of
      fluid to be used in this context remains debated. The aim of our study was to
      compare the amount of fluid challenges required to optimize stroke volume after
      induction of anaesthesia with colloid (HES) or crystalloid (0.9% NaCl). DESIGN:
      Open randomized prospective parallel-group study. PATIENTS AND METHODS: Fifty-six
      adult patients scheduled to undergo orthopaedic surgery under general anaesthesia
      were randomly assigned to receive, either 0.9% NaCl (n=28), or HES (n=28).
      Cardiac preload optimization directed by oesophageal Doppler was performed after
      induction with fluid challenges of 250ml of solution until stroke volume (SV) no
      longer increased by 10%. Primary endpoint was: number of fluid challenges
      required to achieve SV optimization. Secondary endpoints were: number of patients
      responding to the first fluid challenge, proportion of patients requiring
      ephedrine and the ephedrine dose required to restore arterial pressure. RESULTS:
      Percentages of responders were 61% and 63% in the 0.9% NaCl and HES groups,
      respectively. Number of fluid challenges necessary for SV optimization was not
      significantly different between 0.9% NaCl group and HES group (2 [1-2] versus 2
      [1-2], P=0.33). Number of patients needing ephedrine, and well as the associated
      ephedrine dose, did not differ significantly. CONCLUSIONS: Our study suggests
      that after induction, crystalloid and colloid expand the intravascular volume
      with equivalent efficacy immediately after administration and correct in a
      similar way the postinduction hypotension.

PMID- 23867540
TI  - Unilateral permanent loss of vision after nefopam administration.
AB  - Acute glaucoma angle closure is a rare complication of anaesthesia and multimodal
      analgesia. However it is a medical emergency, hence any delay in its treatment
      may have catastrophic consequences. We present a case of postoperative glaucoma,
      which had evolved to permanent blindness. We also reviewed the French
      pharmacovigilance database between 1996 and 2006 and found four other cases of
      acute glaucoma angle closure in postoperative period possibly related to the
      administration of nefopam. 

PMID- 23867541
TI  - In vitro CPC retention and VSC adsorption by IPM oil droplets: possible
      mechanisms of action of a two phase mouthwash.
AB  - Two phase oil-water mouthwash has been previously shown to efficiently bind oral
      microorganisms, relying on their cell surface hydrophobicity. The aim of the
      present in vitro study was to test the cetylpyridinium chloride (CPC) retention
      and volatile sulfide compounds (VSCs) adsorption abilities of the oil droplets
      created by mixing of a two phase oil-water solution. VSC adsorption was assayed
      using a salivary incubation assay and garlic powder solutions, and demonstrated
      using microscopic sulfide assay. CPC retention was assayed by kinetic and
      endpoint measurement of Streptococcus salivarius outgrowth using microplate
      (ELISA) reader. Results showed that the isopropyl myristate (IPM) oil droplets in
      the two phase solutions were able to adsorb 68-80% of VSCs. CPC at a
      concentration of 0.05% was most affectively retained by the oil droplets showing
      a significantly increase in residual antibacterial activity against Streptococcus
      salivarius. These results taken together, suggests that VSC adsorption and CPC
      retention by IPM oil droplets may be two additional mechanisms in the activity of
      the two phase mouthwash formulation. 

PMID- 23867542
TI  - Novel therapeutics for the treatment of familial Mediterranean fever: from
      colchicine to biologics.
AB  - Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is
      characterized by sporadic, paroxysmal attacks of fever and serosal inflammation,
      lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis,
      and skin and oral lesions. Diagnosis is based on clinical features, response to
      treatment with colchicine, and genetic analysis. Colchicine prevents attacks and
      renal amyloidosis, in addition to reversing proteinuria. Nonresponders may
      receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1
      decoy receptor. Recently, new options have been considered.

PMID- 23867543
TI  - Assessment of the cytotoxic, genotoxic, and antigenotoxic potential of
      Pycnogenol(r) in in vitro mammalian cells.
AB  - Pycnogenol(r) (PYC), a standardized plant extract obtained from the bark of the
      French maritime pine Pinus pinaster, has been suggested to exert strong
      antioxidant activity and used as a phytochemical remedy for various diseases. In
      this study, we investigated the antioxidant capacity of PYC by the trolox
      equivalent antioxidant capacity (TEAC) assay and the cytotoxicity by neutral red
      uptake (NRU) test in Chinese Hamster Ovary (CHO) cells. The genotoxic and
      antigenotoxic effects of PYC were evaluated by the cytokinesis-blocked
      micronucleus (CBMN) and alkaline comet assays in human peripheral blood
      lymphocytes. At the concentrations of 2-200 MUg/ml, PYC was found to have
      antioxidant activity. The viability of CHO cells during 24h exposure were not
      affected at the concentrations of 5-150 MUg/ml of PYC. IC50 value of PYC was
      found to be 285 MUg/ml. At the concentrations above 100 MUg/ml, PYC alone induced
      DNA damage and increased MN frequency, although PYC at all concentrations in a
      dose dependent manner revealed a reduction in the frequency of MN and the extent
      of DNA damage induced by H2O2. These results suggest PYC might reduce H2O2
      induced chromosome breakage and loss and DNA damage in cultured human
      lymphocytes.

PMID- 23867544
TI  - Advanced glycation endproducts in food and their effects on health.
AB  - Advanced glycation endproducts (AGEs) form by Maillard-reactions after initial
      binding of aldehydes with amines or amides in heated foods or in living
      organisms. The mechanisms of formation may include ionic as well as oxidative and
      radical pathways. The reactions may proceed within proteins to form high
      molecular weight (HMW) AGEs or among small molecules to form low-molecular weight
      (LMW) AGEs. All free amino acids form AGEs, but lysine or arginine side chains
      dominate AGE formation within proteins. The analysis of AGEs in foods and body
      fluids is most often performed by ELISA or LC-MS; however, none of the
      methodologies cover all HMW and LMW AGEs. Most research is, therefore, carried
      out using 'representative' AGE compounds, most often N(epsilon)-carboxymethyl
      lysine (CML). Only LMW AGEs, including peptide-bound forms, and carbonyls may be
      absorbed from the gut and contribute to the body burden of AGEs. Some AGEs
      interact with specific pro- or anti-inflammatory receptors. Most studies on the
      biological effects of AGEs have been carried out by administering heated foods.
      The pro-inflammatory and deteriorating biological effects of AGEs in these
      studies, therefore, need further confirmation. The current review points out
      several research needs in order to address important questions on AGEs in foods
      and health. 

PMID- 23867545
TI  - Fatty acid profile, oxidative stability and toxicological safety of bayberry
      kernel oil.
AB  - The fatty acid profile, oxidative stability and toxicological safety of bayberry
      (Myrica rubra Sieb. et Zucc.) kernel oil (BKO) extracted by supercritical carbon
      dioxide (SC-CO2) and solvent of diethyl ether were assessed. Fatty acid profile
      was determined by gas chromatography, oxidative stability by placing the sample
      of 25g in a blast oven at 50+/-1 degrees C to accelerate oxidation and
      toxicological safety by bacterial reverse mutation (Ames test) and acute oral
      toxicity in mice. The results demonstrated that in comparison to lard and
      rapeseed oil, the peroxide values of BKO were higher but the acid values were
      similar during the incubation test. The Ames test demonstrated no mutagenicity
      and no obvious acute toxicity were observed, suggesting that the BKO has
      potential as a novel edible oil.

PMID- 23867546
TI  - A systematic review of Bisphenol A "low dose" studies in the context of human
      exposure: a case for establishing standards for reporting "low-dose" effects of
      chemicals.
AB  - Human exposure to the chemical Bisphenol A is almost ubiquitous in surveyed
      industrialized societies. Structural features similar to estrogen confer the
      ability of Bisphenol A (BPA) to bind estrogen receptors, giving BPA membership in
      the group of environmental pollutants called endocrine disruptors. References by
      scientists, the media, political entities, and non-governmental organizations to
      many toxicity studies as "low dose" has led to the belief that exposure levels in
      these studies are similar to humans, implying that BPA is toxic to humans at
      current exposures. Through systematic, objective comparison of our current, and a
      previous compilation of the "low-dose" literature to multiple estimates of human
      external and internal exposure levels, we found that the "low-dose" moniker
      describes exposures covering 8-12 orders of magnitude, the majority (91-99% of
      exposures) being greater than the upper bound of human exposure in the general
      infant, child and adult U.S. Population. "low dose" is therefore a descriptor
      without specific meaning regarding human exposure. Where human exposure data are
      available, for BPA and other environmental chemicals, reference to toxicity study
      exposures by direct comparison to human exposure would be more informative, more
      objective, and less susceptible to misunderstanding. 

PMID- 23867547
TI  - False positivity in HER2 testing of breast cancer: novel paths for approaching an
      old dilemma.
AB  - AIMS: Variability in determining HER2 status has been reported, especially,
      differences in sensitivity and specificity among commercially available
      antibodies, with false positive and false negative results. We compared the
      sensitivity and specificity of five anti-HER2 antibodies by immunohistochemistry
      (IHC), using the new dual colour brightfield in situ hybridisation (DDISH) as the
      gold standard, on invasive breast carcinomas (IBC) arrays. MATERIAL AND METHODS:
      Serial sections from tissue microarrays (TMA) containing 200 preselected primary
      IBC were submitted to DDISH (VENTANA INFORM HER2 Dual ISH assay), and
      immunohistochemistry, using Dako A0485 and HercepTest (polyclonal), Novocastra
      CB11 (mouse monoclonal), NeoMarkers SP3 and Ventana 4B5 (rabbit monoclonal).
      RESULTS: From the initial 200 cases, 184 were assessed by DDISH and IHC. The
      concordance among the antibodies was considered very good (kappa statistics
      varied from 0.82 to 0.9). The overall concordance between IHC and DDISH ranged
      from 94.1% for CB11 to 96.6% for A0485. The antibodies A0485, HercepTest, SP3 and
      4B5 were over 95% sensitive and specific. CB11 was the most specific antibody
      (97.1%). 60% (CB11) to 83.3% (SP3) of the 2+ cases showed no gene amplification
      by DDISH. False negative cases varied from 0.5% (A0485) to 3.8% (CB11) of the
      cases, and false positive from 1.6% (CB11) to 2.7% (HercepTest, SP3 and 4B5) of
      the 184 cases. CONCLUSIONS: There was very good agreement among the five anti
      HER2 antibodies. CB11 was the most specific antibody, but showed more false
      negative cases. A0485, SP3, 4B5 and HercepTest were highly sensitive and
      specific, but showed more false positive cases.

PMID- 23867548
TI  - Influence of exclusive enteral nutrition therapy on bone density and geometry in
      newly diagnosed pediatric Crohn's disease patients.
AB  - BACKGROUND AND AIMS: Exclusive enteral nutrition (EEN) induces remission in
      patients with Crohn's disease (CD). We investigated the short-term impact of EEN
      on bone quality and muscle mass in children with CD. METHODS: Ten newly diagnosed
      CD patients (7 male, 10.6-17.7 years of age) were assessed by peripheral
      quantitative computed tomography (pQCT) at the forearm before starting an 8-weeks
      treatment with EEN, and after 12 and 52 weeks. No steroids or biologicals were
      applied. Trabecular and cortical bone mineral density, total bone, and muscle
      cross-sectional area (CSA) were measured by pQCT and expressed as age- and sex
      specific z-scores; size-dependent CSAs were corrected for low height for age.
      Wilcoxon rank sum test was applied. RESULTS: Remission at week 12 was achieved in
      8 patients; 2 still had mild disease. Initially low trabecular density z-scores
      improved (+0.3; p = 0.006) at week 12; simultaneously, the increased cortical
      density z-scores normalized (-0.4; p = 0.027). The low z-score for muscle CSA
      corrected for height (median -2.5, range -3.49 to -0.97) increased within 12
      weeks (+1.0; p = 0.002) with no further improvement thereafter. CONCLUSIONS: The
      results indicate disturbed bone remodeling and severely impaired muscle mass in
      newly diagnosed CD children. Bone metabolism and muscle mass improved within 3
      months after starting EEN with no further normalization thereafter.

PMID- 23867549
TI  - Liver nodule occurrence in chronic liver disease: HCC unique option?

PMID- 23867550
TI  - Young children's mapping between arrays, number words, and digits.
AB  - This study investigates when young children develop the ability to map between
      three numerical representations: arrays, spoken number words, and digits.
      Children (3, 4, and 5 years old) had to map between the two directions (e.g.,
      array-to-digit vs. digit-to-array) of each of these three representation pairs,
      with small (1-3) and large numbers (4-6). Five-year-olds were at ceiling in all
      tasks. Three-year-olds succeeded when mapping between arrays and number words for
      small numbers (but not large numbers), and failed when mapping between arrays and
      digits and between number words and digits. The main finding was that four-year
      olds performed equally well when mapping between arrays and number words and when
      mapping between arrays and digits. However, they performed more poorly when
      mapping between number words and digits. Taken together, these results suggest
      that children first learn to map number words to arrays, then learn to map digits
      to arrays and finally map number words to digits. These findings highlight the
      importance of directly exploring when children acquire digits rather than
      assuming that they acquire digits directly from number words.

PMID- 23867551
TI  - Expression of cytochrome P450 2A5 in a C57BL/6J mouse model of nonalcoholic fatty
      liver disease.
AB  - Cytochrome P450 2A5 (CYP2A5) expression is induced during the hepatotoxicity
      caused by various hepatotoxins and hepatitis. However, CYP2A5 expression during
      nonalcoholic fatty liver disease (NAFLD) is still unknown. In this study, serum
      biochemical parameters and liver histopathological analyses found that NAFLD had
      developed in C57BL/6J mice via administration of a high-fat diet continuously for
      8 weeks. Subsequently, CYP2A5 expression was probed in the mice diagnosed with
      NAFLD that were treated with or without pyrazole, the inducer of chemical liver
      injury. It is shown that hepatic CYP2A5 mRNA, protein expression and coumarin 7
      hydroxylase activity are enhanced with high-fat feed, and that pyrazole is able
      to further increase CYP2A5 expression and activity in mice with NAFLD. These
      results revealed that CYP2A5 is elevated during NAFLD and suggested that pyrazole
      and NAFLD act synergistically to induce the expression of CYP2A5 via an unclear
      mechanism. 

PMID- 23867553
TI  - Development from childhood to adulthood increases morphological and functional
      inter-individual variability in the right superior temporal cortex.
AB  - We study the developmental trajectory of morphology and function of the superior
      temporal cortex (STC) in children (8-9 years), adolescents (14-15 years) and
      young adults. We analyze cortical surface landmarks and functional MRI (fMRI)
      responses to voices, other natural categories and tones and examine how
      hemispheric asymmetry and inter-subject variability change across age. Our
      results show stable morphological asymmetries across age groups, including a
      larger left planum temporale and a deeper right superior temporal sulcus. fMRI
      analyses show that a rightward lateralization for voice-selective responses is
      present in all groups but decreases with age. Furthermore, STC responses to
      voices change from being less selective and more spatially diffuse in children to
      highly selective and focal in adults. Interestingly, the analysis of
      morphological landmarks reveals that inter-subject variability increases during
      development in the right--but not in the left--STC. Similarly, inter-subject
      variability of cortically-realigned functional responses to voices, other
      categories and tones increases with age in the right STC. Our findings reveal
      asymmetric developmental changes in brain regions crucial for auditory and voice
      perception. The age-related increase of inter-subject variability in right STC
      suggests that anatomy and function of this region are shaped by unique individual
      developmental experiences.

PMID- 23867552
TI  - IL-12p70-producing patient DC vaccine elicits Tc1-polarized immunity.
AB  - BACKGROUND: Systemic administration of IL-12p70 has demonstrated clinical
      activity in cancer patients, but dose-limiting toxicities have hindered its
      incorporation in vaccine formulations. Here, we report on the immunological and
      clinical outcomes upon vaccination with CD40L/IFN-gamma-matured, IL-12p70
      producing DCs. METHODS: 7 HLA-A*0201+ newly diagnosed stage IV melanoma patients
      were immunized against the gp100 melanoma antigen using autologous peptide
      pulsed, CD40L/IFN-gamma-matured DCs. PBMCs were taken weekly for immune
      monitoring by tetramer analysis and functional assays. CT imaging was performed
      at baseline, week 9, and week 18 for clinical assessment using RECIST. RESULTS: 6
      of 7 treated patients developed sustained T cell immunity to all 3 melanoma gp100
      antigen-derived peptides. 3 of the 6 immunological responders developed confirmed
      clinical responses (1 complete remission >4 years, 2 partial response).
      Importantly, DC vaccine-derived IL-12p70 levels positively correlated with time
      to progression (P = 0.019, log-rank), as did T-cytotoxic 1 (Tc1) immunity, as
      assessed by IFN-gamma/IL-13 and IFN-gamma/IL-5 ratios (P = 0.035 and P = 0.030,
      respectively, log-rank). In contrast, a pathway-specific defect in IL-12p35
      transcription was identified upon CD40L/IFN-gamma activation in clinical
      nonresponder patient DCs, and gp100-specific T cells from these patients
      displayed a Tc2 phenotype. Incorporation of TLR3 and TLR8 agonists into the
      CD40L/IFN-gamma activation protocol corrected the IL-12p70 production defect in
      DCs derived from clinical nonresponder patients. CONCLUSION: These findings
      underscore the essential role of IL-12p70 in the development of therapeutic type
      1 antigen-specific CD8+ T cell immunity in humans with cancer.

PMID- 23867554
TI  - Oscillatory correlates of memory in non-human primates.
AB  - The ability to navigate through our environment, explore with our senses, track
      the passage of time, and integrate these various components to form the
      experiences which make up our lives is shared among humans and animals. The use
      of animal models to study memory, coupled with electrophysiological techniques
      that permit the direct measurement of neural activity as memories are formed and
      retrieved, has provided a wealth of knowledge about these mechanisms. Here, we
      discuss current knowledge regarding the specific role of neural oscillations in
      memory, with particular emphasis on findings derived from non-human primates.
      Some of these findings provide evidence for the existence in the primate brain of
      mechanisms previously identified only in rodents and other lower mammals, while
      other findings suggest parallels between memory-related activity and processes
      observed in other cognitive modalities, including attention and sensory
      perception. Taken together, these results provide insight into how network
      activity may be organized to promote memory formation, and suggest that key
      aspects of this activity are similar across species, providing important
      information about the organization of human memory. 

PMID- 23867555
TI  - Repeated stimuli elicit diminished high-gamma electrocorticographic responses.
AB  - In the phenomenon of repetition suppression (RS), when a person views a stimulus,
      the neural activity involved in processing that item is relatively diminished if
      that stimulus had been previously viewed. Previous noninvasive imaging studies
      mapped the prevalence of RS for different stimulus types to identify brain
      regions involved in representing a range of cognitive information. However, these
      noninvasive findings are challenging to interpret because they do not provide
      information on how RS relates to the brain's electrophysiological activity. We
      examined the electrophysiological basis of RS directly using brain recordings
      from implanted electrocorticographic (ECoG) electrodes in neurosurgical patients.
      Patients performed a memory task during ECoG recording and we identified high
      gamma signals (65-128 Hz) that distinguished the neuronal representation of
      specific memory items. We then compared the neural representation of each item
      between novel and repeated viewings. This revealed the presence of RS, in which
      the neuronal representation of a repeated item had a significantly decreased
      amplitude and duration compared with novel stimuli. Furthermore, the magnitude of
      RS was greatest for the stimuli that initially elicited the largest activation at
      each site. These results have implications for understanding the neural basis of
      RS and human memory by showing that individual cortical sites exhibit the largest
      RS for the stimuli that they most actively represent.

PMID- 23867556
TI  - Fast optical signals in the sensorimotor cortex: General Linear Convolution Model
      applied to multiple source-detector distance-based data.
AB  - In this study, we applied the General Linear Convolution Model to detect fast
      optical signals (FOS) in the somatosensory cortex, and to study their dependence
      on the source-detector separation distance (2.0 to 3.5 cm) and irradiated light
      wavelength (690 and 830 nm). We modeled the impulse response function as a
      rectangular function that lasted 30 ms, with variable time delay with respect to
      the stimulus onset. The model was tested in a cohort of 20 healthy volunteers who
      underwent supra-motor threshold electrical stimulation of the median nerve. The
      impulse response function quantified the time delay for the maximal response at
      70 ms to 110 ms after stimulus onset, in agreement with classical somatosensory
      evoked potentials in the literature, previous optical imaging studies based on a
      grand-average approach, and grand-average based processing. Phase signals at
      longer wavelength were used to identify FOS for all the source-detector
      separation distances, but the shortest one. Intensity signals only detected FOS
      at the greatest distance; i.e., for the largest channel depth. There was no
      activation for the shorter wavelength light. Correlational analysis between the
      phase and intensity of FOS further confirmed diffusive rather than optical
      absorption changes associated with neuronal activity in the activated cortical
      volume. Our study demonstrates the reliability of our method based on the General
      Linear Convolution Model for the detection of fast cortical activation through
      FOS.

PMID- 23867558
TI  - The role of neural impulse control mechanisms for dietary success in obesity.
AB  - Deficits in impulse control are discussed as key mechanisms for major worldwide
      health problems such as drug addiction and obesity. For example, obese subjects
      have difficulty controlling their impulses to overeat when faced with food items.
      Here, we investigated the role of neural impulse control mechanisms for dietary
      success in middle-aged obese subjects. Specifically, we used a food-specific
      delayed gratification paradigm and functional magnetic resonance imaging to
      measure eating-related impulse-control in middle-aged obese subjects just before
      they underwent a twelve-week low calorie diet. As expected, we found that
      subjects with higher behavioral impulse control subsequently lost more weight.
      Furthermore, brain activity before the diet in VMPFC and DLPFC correlates with
      subsequent weight loss. Additionally, a connectivity analysis revealed that
      stronger functional connectivity between these regions is associated with better
      dietary success and impulse control. Thus, the degree to which subjects can
      control their eating impulses might depend on the interplay between control
      regions (DLPFC) and regions signaling the reward of food (VMPFC). This could
      potentially constitute a general mechanism that also extends to other disorders
      such as drug addiction or alcohol abuse. 

PMID- 23867557
TI  - Concurrent TMS to the primary motor cortex augments slow motor learning.
AB  - Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool,
      with one FDA approved use. While TMS alone is able to up- (or down-) regulate a
      targeted neural system, we argue that TMS applied as an adjuvant is more
      effective for repetitive physical, behavioral and cognitive therapies, that is,
      therapies which are designed to alter the network properties of neural systems
      through Hebbian learning. We tested this hypothesis in the context of a slow
      motor learning paradigm. Healthy right-handed individuals were assigned to
      receive 5 Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor
      cortex (M1) as they performed daily motor practice of a digit sequence task with
      their non-dominant hand for 4 weeks. Resting cerebral blood flow (CBF) was
      measured by H2(15)O PET at baseline and after 4 weeks of practice. Sequence
      performance was measured daily as the number of correct sequences performed, and
      modeled using a hyperbolic function. Sequence performance increased significantly
      at 4 weeks relative to baseline in both groups. The TMS group had a significant
      additional improvement in performance, specifically, in the rate of skill
      acquisition. In both groups, an improvement in sequence timing and transfer of
      skills to non-trained motor domains was also found. Compared to the sham group,
      the TMS group demonstrated increases in resting CBF specifically in regions known
      to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus,
      and cerebellum. These results indicate that TMS applied concomitantly augments
      behavioral effects of motor practice, with corresponding neural plasticity in
      motor sequence learning network. These findings are the first demonstration of
      the behavioral and neural enhancing effects of TMS on slow motor practice and
      have direct application in neurorehabilitation where TMS could be applied in
      conjunction with physical therapy.

PMID- 23867559
TI  - Functional and structural syntax networks in aging.
AB  - Language abilities are known to deteriorate in aging, possibly related to
      decreased functional and structural connectivity within specialized brain
      networks. Here, we investigated syntactic ability in healthy young and older
      adults using a comprehensive assessment of behavioral performance, task
      independent functional (FC) and structural brain connectivity (SC). Seed-based FC
      originating from left pars opercularis (part of Broca's area) known to support
      syntactic processes was assessed using resting-state functional magnetic
      resonance imaging, and SC using fractional anisotropy from diffusion weighted
      imaging, in the dorsally located superior longitudinal and the ventrally located
      uncinate fasciculi (SLF, UF) and forceps minor. Young compared to older adults
      exhibited superior syntactic performance and stronger FC within the mainly left
      lateralized syntax network, which was beneficial for performance. In contrast, in
      older adults, FC within the mainly left-lateralized syntax network was reduced
      and did not correlate with performance; inter-hemispheric FC to right inferior
      frontal and angular gyri was detrimental for performance. In both groups,
      performance was positively correlated with inter-hemispheric SC. For intra
      hemispheric SC, performance correlated with structural integrity of SLF in young
      adults and with integrity of UF in older adults. Our data show that reduced
      syntactic ability in older adults is associated with decreased FC within
      dedicated syntax networks. Moreover, young adults showed an association of
      syntactic ability with structural integrity of the dorsal tract, while older
      adults rely more on ventral fibers. In sum, our study provided novel insight into
      the relationship between connectivity and syntactic performance in young and
      older adults. In addition to elucidating age-related changes in syntax networks
      and their behavioral relevance, our results contribute to a better understanding
      of age-related changes in functional and structural brain organization in
      general, an important prerequisite for developing novel strategies to counteract
      age-related cognitive decline. 

PMID- 23867560
TI  - Prevalence of latent tuberculosis infection and its risk factors in
      schoolchildren and adolescents in Shanghai, China.
AB  - OBJECTIVES: As tuberculosis (TB) infection in childhood contributes to the pool
      of individuals with latent tuberculosis infection (LTBI) from which future
      tuberculosis cases arise, this study aimed to determine the prevalence and risk
      factors associated with LTBI in schoolchildren and adolescents from Shanghai,
      China. METHODS: In this cross-sectional study, we administered T-SPOT.TB and TB
      infection risk factor questionnaire to children and adolescents aged between 10
      and 18 years in 2010 in Shanghai. LTBI cases were defined by positive T-SPOT.TB
      test results and X-ray confirmation. RESULTS: A total of 1106 schoolchildren and
      adolescents were enrolled, of which 46.1% were male, and 91.8% were vaccinated
      with Bacille Calmette Guerin (BCG). Overall, 52 (4.7%) children had a positive T
      SPOT.TB result, with significant increase in age distribution. However, none of
      the participants demonstrated TB-related abnormality on X-ray examination.
      Multivariate analysis showed that LTBI was associated with no BCG vaccination
      (odds ratio: 2.40; 95% confidence interval: 1.182-5.335) and a history of TB
      exposure (odds ratio: 6.89; 95% confidence interval: 3.095-15.35). For 46
      children and adolescents with history of TB exposure, contact hours per week of
      TB cases were significantly associated with risk of LTBI. CONCLUSIONS: Prevalence
      of LTBI in schoolchildren and adolescents in Shanghai is relatively low compared
      with other high epidemic areas of TB. A higher risk of LTBI was observed among
      children with no BCG vaccination and those with a history of TB exposure, which
      suggests that the prevalence of LTBI among schoolchildren could be further
      reduced by strengthening BCG vaccination under the national immunization
      programme and enhancing contact investigation of active TB patients.

PMID- 23867561
TI  - Validation of the SDQ in a multi-ethnic population of young children.
AB  - BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is a valuable
      screening tool for identifying psychosocial problems. Its performance in a multi
      ethnic society, common to many paediatric health care workers, has not been
      investigated. Because it is important that screening instruments are valid and
      reliable for all ethnic groups within one society, we examined differences in the
      SDQ's psychometric properties in a multi-ethnic society. METHODS: The SDQ parent
      (n = 8114) and teacher form (n = 9355) were completed as part of a preventive
      health check for children aged 5-6 years of Dutch and non-Dutch ethnic
      backgrounds. The Child Behaviour Checklist (CBCL)/Teacher Report Form (TRF) was
      administered to a subsample. RESULTS: Factor analysis of the parent-rated SDQ
      showed different rating patterns for two of the five subscales for non-Dutch
      children as compared with Dutch children. Cronbach's alpha for the total
      difficulties score varied by ethnic group (0.73-0.78 parent-rated SDQ, 0.80-0.83
      teacher-rated SDQ), and coefficients were generally smaller for non-Dutch than
      for Dutch children (P < 0.05). Alpha coefficients for subscales varied between
      0.31-0.85 for ethnic groups. Inter-rater correlations between parents and
      teachers for the total difficulties score varied between 0.20-0.41 between ethnic
      groups and were larger for Dutch than for non-Dutch children (P < 0.05).
      Concurrent validity was acceptable for most scales and most ethnic groups.
      CONCLUSION: The total difficulties score of the parent- and teacher-rated SDQ is
      valid and reliable for different ethnic groups within Dutch society. However,
      there are differences in reliability and validity of the subscales, which makes
      interpretation of the subscales difficult for certain ethnic groups.

PMID- 23867562
TI  - European public health research in Horizon 2020.

PMID- 23867563
TI  - European Health Examination Survey--towards a sustainable monitoring system.
AB  - BACKGROUND:  Health examination surveys (HESs), including both questionnaire and
      physical measurements, and in most cases also collection of biological samples,
      can provide objective health indicators. This information complements data from
      health interview surveys and administrative registers, and is important for
      evidence-based planning of health policies and prevention activities. HESs are
      valuable data sources for research. The first national HESs in Europe were
      conducted in the late 1950s and early 1960s. They have recently been carried out
      in an increasing number of countries, but there has been no joint standardization
      between the countries. METHODS: The European Health Examination Survey Pilot
      Project was conducted in 2009-2012. The European Health Examination Survey Pilot
      Reference Centre was established and pilot surveys were conducted in 12
      countries. RESULTS:  European standardized protocols for key measurements on main
      chronic disease risk factors (height, weight, waist circumference, blood
      pressure, blood lipids and fasting glucose or HbA1c) were prepared. European
      level training and external quality assessment were organized. Although the level
      of earlier experience, infrastructures, economic status and cultural settings
      varied between the pilot countries, it was possible to standardize measurements
      of HESs across the populations. Obtaining high participation rates was
      challenging. CONCLUSION:  HESs provide high-quality and representative population
      data to support policy decisions and research. For future national HESs,
      centralized coordination, training and external quality assessment are needed to
      ensure comparability of the results. Further studies on effects of different
      survey methods on comparability of the results and on recruitment and motivation
      of survey participants are needed.

PMID- 23867564
TI  - Social networks, social participation and self-perceived health among older
      people in transitional Kosovo.
AB  - BACKGROUND: A number of studies proved that social networks and social
      participation have beneficial health effects in western countries. However, the
      evidence from southeast European region is scant. We aimed to assess the extent
      of social networks and social participation and their relationship with self
      perceived health status among older people in post-war Kosovo. METHODS: A
      nationwide cross-sectional study was conducted in Kosovo in 2011 including a
      representative sample of 1890 individuals aged >=65 years (949 men, mean age 73
      +/- 6 years; 941 women, mean age 74 +/- 7 years; response rate: 83%). Social
      networks were assessed by means of number of friends and family members that
      participants had contacts with, whereas social participation by involvement in
      social groupings/organizations. Information on self-perceived health status and
      demographic and socioeconomic characteristics was also collected. RESULTS:
      Overall, 93% of study participants reported that they had at least weekly
      contacts with more than one family member, and 97% reported daily contacts with
      their respective friends. Conversely, only 14% of participants reported
      engagement with social groupings. Generally, individuals who had contacts with
      friends and/or engaged with social organizations reported a better health status.
      CONCLUSION: Our findings point to strong family ties in this patriarchal society.
      Conversely, levels of social participation were considerably lower in Kosovo
      compared with the western European countries. The low participation levels in
      social groupings and their putative deleterious health effects should raise the
      awareness of policymakers to improve the conditions and increase the degree of
      social participation among older people in transitional Kosovo.

PMID- 23867565
TI  - Interleukin-6 and oncostatin-M synergize with the PI3K/AKT pathway to promote
      aggressive prostate malignancy in mouse and human tissues.
AB  - Chronic inflammation has been proposed as an etiological and progression factor
      in prostate cancer. In this study, we used a dissociated prostate tissue
      recombination system to interrogate the role of interleukin 6 (IL6) and the
      related cytokine oncostatin-M (OSM) in the initiation and progression of prostate
      cancer. We identified that prostatic intraepithelial neoplasia (PIN) lesions
      induced by PTEN loss of function (PTEN(LOF)) progress to invasive adenocarcinoma
      following paracrine expression of either cytokine. Increased expression of OSM
      was also able to drive progression of benign human epithelium when combined with
      constitutively activated AKT. Malignant progression in the mouse was associated
      with invasion into the surrounding mesenchyme and increased activation of STAT3
      in PTEN(LOF) grafts expressing IL6 or OSM. Collectively, our work indicates that
      pro-inflammatory cytokines such as IL6 or OSM could activate pathways associated
      with prostate cancer progression and synergize with cell-autonomous oncogenic
      events to promote aggressive malignancy. IMPLICATIONS: Increased expression of
      IL6 or OSM synergizes with loss of PTEN to promote invasive prostate cancer.
      VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/early/2013/09/02/1541
      7786.MCR-13-0238/F1.large.jpg.

PMID- 23867566
TI  - Visual search for faces by race: a cross-race study.
AB  - Using a single averaged face of each race previous study indicated that the
      detection of one other-race face among own-race faces background was faster than
      vice versa (Levin, 1996, 2000). However, employing a variable mapping of face
      pictures one recent report found preferential detection of own-race faces vs.
      other-race faces (Lipp et al., 2009). Using the well-controlled design and a
      heterogeneous set of real face images, in the present study we explored the
      visual search for own and other race faces in Chinese and Caucasian participants.
      Across both groups, the search for a face of one race among other-race faces was
      serial and self-terminating. In Chinese participants, the search consistently
      faster for other-race than own-race faces, irrespective of upright or upside-down
      condition; however, this search asymmetry was not evident in Caucasian
      participants. These characteristics suggested that the race of a face is not a
      visual basic feature, and in Chinese participants the faster search for other
      race than own-race faces also reflects perceptual factors. The possible mechanism
      underlying other-race search effects was discussed. 

PMID- 23867567
TI  - Discomfort and the cortical haemodynamic response to coloured gratings.
AB  - In five experiments we measured the amplitude of the haemodynamic response to
      visual patterns using near infrared spectroscopy of the visual cortex. The
      patterns were gratings with bars that differed in chromaticity but not in
      luminance. In all experiments, with a wide range of chromaticities of the grating
      bars, the amplitude of the haemodynamic response increased with the separation of
      the chromaticities in the CIE 1976 UCS diagram. The amplitude did not vary
      consistently with the cone activation, or with the signal in colour difference
      channels. In four further experiments, again with a wide range of chromaticities,
      the gratings were rated for visual comfort. Discomfort increased consistently
      with the separation of the chromaticities. Given that a large haemodynamic
      response to patterns is generally associated with headache, we suggest that the
      discomfort may be a homeostatic signal to reduce sustained metabolic load on the
      visual cortex. 

PMID- 23867568
TI  - Individuals exhibit idiosyncratic eye-movement behavior profiles across tasks.
AB  - The purpose of this study was to examine individual differences in eye-movement
      behavior. Six metrics (Fixation Rate, Duration, and Size; Saccade Amplitude;
      Micro-Saccade Rate and Amplitude) were used to measure individuals' eye-movement
      behavior profiles (EmBP). We replicate previous research (Andrews & Coppola,
      1999; Castelhano & Henderson, 2008) by finding consistent individual differences
      in fixation duration and saccade amplitude across tasks, and present new findings
      of stable idiosyncrasies in measures of fixational eye-movement (Fixation Size,
      Micro-Saccade Rate and Amplitude). Moreover, we observed consistent inter-metric
      correlations across tasks (e.g., individuals that exhibited relatively high
      Fixation Rates also presented relative low Micro-Saccade Rates and relatively
      high Micro-Saccade Amplitudes). Factor Analysis linked the six EmBP metrics
      together with a single factor, which we speculate might be related to the
      operational effectiveness of the attentional system, given that individual factor
      scores were correlated with scores on a self-report measure of attentional
      function. Normal subjects with relatively high scores on this attention-deficit
      measure exhibited relatively frequent fixations of short duration and large
      spatial extent, and relatively infrequent micro-saccades of large amplitude. This
      EmBP is similar to a general pattern of eye-movement behavior observed with ADHD
      individuals - difficulty controlling eye movements, maintaining fixation, and
      inhibiting intrusive saccades. Results of this study indicate that normal
      individuals exhibit idiosyncratic EmBPs that are quite stable across tasks and
      are related to attentional ability. 

PMID- 23867569
TI  - The sonographic appearance of benign and malignant thyroid diseases and their
      histopathology correlate: demystifying the thyroid nodule.
AB  - The thyroid gland is one of the largest endocrine glands in the human body. It
      functions as a regulator of metabolism. Diseases involving the thyroid range from
      benign to malignant and can be associated with major morbidity and mortality.
      Ultrasound (US) imaging of the thyroid gland is prompted because of a palpable
      mass on clinical examination; abnormality of thyroid function tests; incidental
      finding on other imaging modalities, that is, nuclear scintigraphy or computed
      tomography scan; screening for patients with risk factors for malignancy, such as
      multiple endocrine neoplasia type II; or prior neck radiation
      treatment.Ultrasound is an excellent, noninvasive, and cost-effective diagnostic
      tool in the detection and characterization of thyroid disease. Most thyroid
      diseases have pathognomonic features on US, which are of diagnostic importance
      and lead to appropriate clinical management. Ultrasound plays an important role
      in differentiating benign from malignant thyroid disease, thereby triaging
      patients for US-guided fine-needle aspiration. Ultimately, thyroid US, in
      conjunction with thyroid function tests, can aid in characterizing various
      thyroid diseases.The main objective of this pictorial essay is to illustrate the
      sonographic appearance of various benign and malignant diseases of the thyroid
      with their histopathology correlations. Management of thyroid nodules using US
      guided fine-needle aspiration is also briefly discussed. 

PMID- 23867570
TI  - Multimodality 3-dimensional volumetric ultrasound in obstetrics and gynecology
      with an emphasis in HDlive technique.
AB  - HDlive (high-definition live or real-time US), a new ultrasound software,
      combines a movable virtual adjustable light source in a software that calculates
      the proportion of light reflecting through surface structures, depending on light
      direction. The light source can be manually positioned to illuminate the desired
      area of interest. The ultrasound technician can control light intensity to create
      shadows that enhance image quality. HDlive is an innovation that will render even
      more realistic images of fetal anatomy and of gynecologic lesions. The full
      potential of this new technology is yet to be determined and deserves scientific
      evaluation. 

PMID- 23867571
TI  - Acute torsion of a retroperitoneal renal transplant mimicking renal vein
      thrombosis.
AB  - When imaging a renal transplant, the combination of absent flow in the main renal
      vein and reversed diastolic flow in the intrarenal arteries is considered highly
      suggestive of renal vein thrombosis. We present a case of torsion of a transplant
      kidney presenting with identical findings. Renal transplant torsion in general is
      a rare entity, previously described only in intraperitoneally placed organs; this
      case is the first that we are aware of with torsion occurring in a
      retroperitoneally placed graft. 

PMID- 23867573
TI  - ACR Appropriateness Criteria(r) growth disturbances - risk of intrauterine growth
      restriction.
AB  - Fetal growth disturbances include fetuses at risk for intrauterine growth
      restriction. These fetuses may have an estimated fetal weight at less than the
      10% or demonstrate a plateau of fetal growth with an estimated fetal growth
      greater than the 10%. Uteroplacental insufficiency may play a major role in the
      etiology of intrauterine growth restriction. Fetuses at risk for intrauterine
      fetal growth restriction are susceptible to the potential hostility of the
      intrauterine environment leading to fetal hypoxia and fetal acidosis. Fetal well
      being can be assessed using biophysical profile, Doppler velocimetry, fetal heart
      rate monitoring, and fetal movement counting.Fetal growth disturbances include
      fetuses at risk for intrauterine growth restriction. These fetuses may have an
      estimated fetal weight at less than the 10% or demonstrate a plateau of fetal
      growth with an estimated fetal growth greater than the 10%. Uteroplacental
      insufficiency may play a major role in the etiology of intrauterine growth
      restriction. Fetuses at risk for intrauterine fetal growth restriction are
      susceptible to the potential hostility of the intrauterine environment leading to
      fetal hypoxia and fetal acidosis. Fetal well-being can be assessed using
      biophysical profile, Doppler velocimetry, fetal heart rate monitoring, and fetal
      movement counting.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- 23867574
TI  - Expert opinion on chemotherapy use in castration-resistant prostate cancer
      progressing after docetaxel.
AB  - The term castration-resistant prostate cancer (CRPC) encompasses a wide variety
      of patients with different prognoses. The combination of docetaxel and prednisone
      is considered as the standard first-line chemotherapy. For years, patients
      progressing on docetaxel have been managed with second- and third-line hormone
      therapies, re-treatment with docetaxel, or combined mitoxantrone and prednisone.
      Recently published results of four studies using different drugs: cabazitaxel
      (CBZ), abiraterone (AA), enzalutamide (ENZ), and radium 223, showed an increased
      survival in such patients. In this article, authors make some considerations
      about criteria guiding the choice of a second-line chemotherapy after docetaxel
      in patients with metastatic CRPC, and propose an algorithm based on scientific
      evidence and consensus for rational use of cabazitaxel in this scenario. 

PMID- 23867575
TI  - [Premature infants bronchopulmonary dysplasia: past and present].
AB  - Bronchopulmonary dysplasia (BPD) is the most common chronic respiratory disease
      in premature infants. BPD was first described by Northway in 1967 as a chronic
      respiratory condition that developed in premature infants exposed to mechanical
      ventilation and high oxygen supplementation. DBP is currently defined by the need
      for supplemental oxygen at 28 days of life (mild BPD) and at the 36 weeks of post
      menstrual age (moderate and severe BPD). With the advances of neonatal care,
      epidemiological characteristics and mechanisms of the disease as well as
      pathological characteristics and clinical course have profoundly changed within
      the last two decades, but still no effective curative treatment exists and BPD
      continue to occur among 10 to 20% of premature infants. Furthermore, BPD is a
      significant source of respiratory and neuro-cognitive morbidities. Thus, its
      treatment makes a considerable demand on health services. Regarding its
      pathophysiological mechanisms, it is now established that BPD is a complex
      disease combining genetic susceptibility and environmental injuries. The
      identification of genetic variants involved in BPD is a potential source of
      innovative development in terms of diagnosis and treatment. Indeed, no curative
      or effective prophylactic therapeutic exists and BPD treatment is currently
      symptomatic.

PMID- 23867576
TI  - The role of matrix metalloproteinase-2 in the treatment of atrial fibrillation
      recurrence after a radiofrequency modified maze procedure.
AB  - BACKGROUND AND OBJECTIVE: Our study aimed to elucidate the potential clinical and
      molecular issues in recurrent atrial fibrillation (AF) following a radiofrequency
      modified maze procedure in patients with rheumatic valvular disease and
      persistent AF. METHODS AND RESULTS: Eighty patients with rheumatic valvular
      disease and persistent AF (lasting more than 6 months) who had undergone a
      radiofrequency modified maze procedure and mitral valve replacement were enrolled
      into this single-center pilot study and were followed up for another 6 months.
      Their clinical characteristics were analyzed and the expression of matrix
      metalloproteinase (MMP)-2 including its specific inhibitor and collagen volume
      fraction (CVF) was also assessed. During the 6-month follow-up, 24 subjects had
      recurrent AF. Among them, the left atrial diameter was larger compared to that
      achieved in sinus rhythm (SR). The mRNA and protein expression of MMP-2 was
      significantly increased in recurrent AF patients, while its specific inhibitor
      did not show a significant difference (p > 0.05). The CVF of type I collagen
      increased significantly in the recurrent AF patients compared to SR patients
      (18.16 +/- 3.22 vs. 11.66 +/- 3.38, p < 0.001), whereas the CVF of type III
      collagen showed no significant difference (8.33 +/- 3.44 vs. 9.55 +/- 3.67, p >
      0.05). CONCLUSION: This study suggests that the overexpression of MMP-2 is
      associated with CVF-I in the left atrial appendage which potentially leads to the
      recurrence of AF following a radiofrequency modified maze procedure in patients
      with rheumatic valve disease.

PMID- 23867577
TI  - Radiation mapping inside the bunkers of medium energy accelerators using a
      robotic carrier.
AB  - The knowledge of ambient and peak radiation levels prevailing inside the bunkers
      of the accelerator facilities is essential in assessing the accidental human
      exposure inside the bunkers and in protecting sensitive electronic equipments by
      minimizing the exposure to high intensity mixed radiation fields. Radiation field
      mapping dynamically, inside bunkers are rare, though generally dose-rate data are
      available in every particle accelerator facilities at specific locations. Taking
      into account of the fact that the existing neutron fields with a spread of energy
      from thermal up to the energy of the accelerated charged projectiles, prompt
      photons and other particles prevailing during cyclotron operation inside the
      bunkers, neutron and gamma survey meters with extended energy ranges attached to
      a robotic carrier have been used. The robotic carrier movement was controlled
      remotely from the control room with the help of multiple visible range optical
      cameras provided inside the bunkers and the wireless and wired protocols of
      communication helped its movement and data acquisition from the survey meters.
      Variable Energy Cyclotron Centre, Kolkata has positive ion accelerating
      facilities such as K-130 room Temperature Cyclotron, K-500 Super Conducting
      Cyclotron and a forthcoming 30 MeV Proton Medical Cyclotron with high beam
      current. The dose rates data for K-130 Room Temperature Cyclotron, VECC were
      collected for various energies of alpha and proton beams losing their total
      energy at different stages on different materials at various strategic locations
      of radiological importance inside the bunkers. The measurements established that
      radiation levels inside the machine bunker dynamically change depending upon the
      beam type, beam energy, machine operation parameters, deflector condition, slit
      placement and central region beam tuning. The obtained inference from the
      association of dose rates with the parameters like beam intensity, type and
      energy of projectiles, helped in improving the primary beam transmission and
      minimizing the ambient radiation fields inside the bunkers.

PMID- 23867578
TI  - Reply to comment on: Is the renoprotective effect of erythropoietin in chronic
      kidney disease a myth?

PMID- 23867579
TI  - Pulmonary infection, and not systemic inflammation, accounts for increased
      concentrations of exhaled nitric oxide in patients with septic shock.
AB  - Nitric oxide (NO) is a key mediator in the pathophysiology of septic shock that
      can be measured in exhaled breath. To assess whether a pulmonary infection itself
      or systemic inflammation is responsible for NO production, we determined exhaled
      NO in ventilated patients with respiratory and non-respiratory septic shock and
      compared it with the concentration in ventilated intensive care patients without
      systemic inflammation. In addition, the change of NO production over time and
      correlations with haemodynamic instability were evaluated. The controls without
      systemic inflammation, as witnessed by the absence of systemic inflammatory
      response syndrome criteria and low levels of interleukin-6, had similar
      concentrations of NO as the patients with non-respiratory septic shock. The
      respiratory sepsis patients exhaled more NO than the non-respiratory sepsis
      patients (p = 0.05), and a time dependent decline in time in both groups (p =
      0.04). Exhaled NO did not correlate with markers of disease severity, systemic
      inflammation and haemodynamic instability. These data indicate that the infected
      lungs are the source of exhaled NO. 

PMID- 23867581
TI  - Heart surgery stems increased nutritional risk, expressed during the course of
      stationary rehabilitation.
AB  - BACKGROUND: Cardiovascular diseases are a vast global health burden. Despite
      common prevalence, current knowledge and investigations concerning nutritional
      aspects are limited. Characteristics and dynamics of nutritional risk are not
      entirely known for most of the entities, disease stages or treatment-induced
      fluctuations. This study assessed the effects of heart surgery on unintentional
      weight loss and nutritional risk using the NRS-2002. METHODS: A noninterventional
      study that included patients scheduled for rehabilitation 1-6 months after heart
      surgery was performed. Evaluation included routine cardiovascular diagnostics and
      review of medical histories. Documented baseline weight was available for >85% of
      the patients. Nutritional risk screening was performed with the standardized NRS
      2002 questionnaire. RESULTS: A total of 145 patients were involved, with a mean
      age of 65.3 +/- 11.5 years in a range of 23-84 years. The male to female ratio
      was 121:24 (83.4%:16.6%), respectively. Coronary artery bypass graft surgery
      (CABG) was performed in 89 patients (61.4%), valvular surgery (VS) in 34 (23.4%)
      and combined operations (CABG + VS) in 22 (15.2%). Percentage weight loss history
      was 11.1 +/- 3.4% in a range of 0-20.1%, while NRS-2002 was 4.77 +/- 1.05 in a
      range of 1-6. Increased nutritional risk (NRS-2002 >=3) was found in nearly all
      patients. Combined ischemic and valvular etiology displayed the highest values of
      NRS-2002 (5.0 +/- 1.2). Patient age and creatinine showed significant
      correlations with NRS-2002 (Rho = 0.521, p < 0.001 and Rho = 0.335, p < 0.001,
      respectively). CONCLUSION: Increased nutritional risk was found to be frequently
      prevalent in patients scheduled for rehabilitation after heart surgery. Risk was
      found to be in relation with underlying coronary artery disease as well as with
      the age of patients and parameters of renal function. Routine application of
      nutritional risk screening appears to be a valuable clinical tool for detecting
      this relevant comorbidity, particularly since no connection was found with
      traditional anthropometrics.

PMID- 23867580
TI  - High prevalence of contralateral ankle abnormalities in association with knee
      osteoarthritis and malalignment.
AB  - OBJECTIVE: To evaluate ankle joint abnormalities in a knee osteoarthritis (OA)
      cohort. METHODS: Participants (n = 159) with symptomatic and radiographic OA in
      at least one knee underwent technetium-99m methylene diphosphonate bone scan
      (scored 0-3) of the ankles and forefeet. Knee radiographs were graded for OA
      features of joint space narrowing (JSN) and osteophyte (OST). Ankle symptoms and
      history of ankle injury were assessed by self-report. Knee alignment was measured
      from a long-limb radiograph. Ankle radiographs were obtained on those who
      returned for follow-up (n = 138) and were graded for ankle tibiotalar JSN and
      OST. DESIGN: Ankle scintigraphic abnormalities were frequent (31% of individuals,
      one-third bilateral). Ankle symptoms were reported by 23% of individuals and
      history of ankle injury by 24%. Controlling for gender, age, body mass index
      (BMI), and contralateral predictor, ankle scintigraphic abnormalities were
      associated with: ipsilateral ankle symptoms (P = 0.005); contralateral knee JSN
      (P = 0.001), knee OST (P = 0.006) and knee malalignment (P = 0.08); and history
      of ankle injury or surgery of either ankle (P < 0.0001). At follow-up,
      scintigraphic abnormalities of the ankle were strongly associated with presence
      of tibiotalar radiographic OA (P < 0.0001). CONCLUSIONS: Although considered
      rare, we observed a high prevalence of radiographic features of ankle OA in this
      knee OA cohort. History of overt ankle injury did not appear to account for the
      majority of ankle abnormalities. These results are consistent with a probable
      kinematic association of knee OA pathology and contralateral ankle abnormalities
      and suggest that interventions targeting mechanical factors may be needed to
      prevent ankle OA in the setting of knee OA.

PMID- 23867583
TI  - Current diagnosis and treatment of gastric cancer: where East meets West.

PMID- 23867582
TI  - Expression of glutathione peroxidase 2 is associated with not only early
      hepatocarcinogenesis but also late stage metastasis.
AB  - Understanding of mechanisms of cancer progression is very important for reduction
      of cancer mortality. Of six rat hepatocellular carcinoma (HCC) cell lines,
      differing in their metastatic potential to the lung after inoculation into the
      tail vein of nude mice, the most metastatic featured particular overexpression of
      glutathione peroxidase 2 (GPX2). Therefore, we analyzed the influence of
      interference in highly metastatic L2 cells by siRNA transfection. Gpx2 siRNA
      significantly inhibited cell proliferation at 24 and 48h time points with
      induction of apoptosis but not cell cycle arrest. High expression of mutated p53
      was detected in all HCC cell lines, with reduction in Gpx2 siRNA-transfected
      cells. Migration and invasion in vitro were also suppressed as compared to
      control siRNA-transfected cells and secretion of matrix metalloproteinase 9 was
      reduced. In vivo, the numbers and areas of metastatic nodules per area in the
      lungs were significantly reduced in the mice inoculated with Gpx2 siRNA
      transfected cells as compared to control siRNA-transfected cells. In conclusion,
      expression of GPX2 is associated with cancer metastasis from rat HCCs both in
      vitro and in vivo. Together with immunohistochemical findings of elevated
      expression in rat and also human liver lesions, the results point to important
      roles in hepatocarcinogenesis. 

PMID- 23867584
TI  - Surgery for gastric cancer: has the East versus West issue been solved?

PMID- 23867585
TI  - Lymph node dissection in resectable advanced gastric cancer.
AB  - The extent of surgery for gastric cancer has been debated since Billroth
      performed his first gastrectomy in 1881. This review gives an overview of the
      available literature on the extent of gastrectomy and lymphadenectomy for
      advanced resectable gastric cancer. Subtotal gastrectomy is associated with lower
      morbidity and mortality compared with total gastrectomy, without compromising
      long-term survival. However, a positive resection margin decreases the chance of
      curation. Frozen section examination may prevent this. For poorly differentiated
      singlet ring cell tumors, there may be an argument to perform a total gastrectomy
      in all cases. In 1981, the Japanese Research Society for the Study of Gastric
      Cancer provided guidelines for the standardization of surgical treatment and
      pathological evaluation of gastric cancer. Since then, D2 lymph node dissections
      have become the standard of care in Japan. Because of the superior stage-specific
      survival rates in Japan, a D2 dissection was evaluated in several Western
      randomized controlled trials, but no survival benefit was found for a D2 over a
      D1 dissection. This might be explained by the increased mortality in the D2
      dissection groups which might be the result of a standard pancreaticosplenectomy
      and low experience with D2 dissections. Adding the removal of the para-aortic
      nodes to a D2 dissection does not further improve survival. The removal of lymph
      node stations 10 and 11 by splenectomy showed an increased morbidity, no survival
      benefit, and a very poor prognosis if lymph nodes were affected. Therefore,
      pancreaticosplenectomy should only be performed in cases of tumor invasion into
      these organs. A D2 dissection without routine splenectomy and pancreatic tail
      resection in experienced hands should be considered standard of care for advanced
      resectable gastric cancer, both in Asian and in Western patients. Centralization
      and auditing may further improve outcomes after gastrectomy. 

PMID- 23867586
TI  - Sentinel node navigation surgery in patients with early gastric cancer.
AB  - Clinical application of sentinel node (SN) mapping in patients with early gastric
      cancer has been a controversial issue for years. However, a recent meta-analysis
      and a prospective multicenter trial of SN mapping for early gastric cancer have
      shown acceptable SN detection rates and accuracy of determination of lymph node
      status. A dual-tracer method that utilizes radioactive colloids and blue dyes is
      currently considered the most reliable method for the stable detection of SNs in
      patients with early gastric cancer. However, new technologies such as indocyanine
      green infrared or fluorescence imaging might revolutionize the SN mapping
      procedures in gastric cancer. For early-stage gastric cancer such as cT1N0, for
      which a better prognosis can be potentially achieved through conventional
      surgical approaches, the establishment of individualized, minimally invasive
      treatments that may retain the patients' quality of life should be the next
      surgical challenge. Although there are many unresolved technical issues,
      laparoscopic SN biopsy with laparoscopic minimized gastrectomy or endoscopic
      mucosal resection/endoscopic submucosal dissection could be a promising strategy
      to achieve this goal. 

PMID- 23867587
TI  - (Neo)-adjuvant chemo(-radio) therapy for adenocarcinomas of the gastroesophageal
      junction and the stomach in the West.
AB  - Worldwide, the treatment of adenocarcinomas of the gastroesophageal junction and
      stomach has changed over the past decades. It is no longer surgery alone.
      Nowadays, most patients undergo surgery plus pre- and/or postoperative therapies.
      However, there are still marked differences in surgical procedures between the
      East and the West which might influence the surgical prognosis and thereby also
      the choice of perioperative treatment strategies. In the East, with its more
      extended surgical procedures, including standard D2 dissections, the current
      treatment philosophy is primary surgery followed by adjuvant chemotherapy.
      Neoadjuvant approaches are restricted to really advanced tumors, and
      perioperative chemoradiation is not routinely used (at least to date). This
      clearly differs from treatment strategies currently recommended in Western
      countries. In Europe and North America, pre- plus postoperative chemotherapy has
      become the recommended treatment for locally more advanced tumors, and
      preoperative chemoradiation is increasingly administered to patients with
      adenocarcinomas of the gastroesophageal junction (Siewert type I/II). However,
      the role of postoperative chemotherapy (despite its increasing use) is still
      under discussion in the West (especially Europe) and not generally
      recommended/accepted as a standard treatment. Postoperative chemoradiation, which
      is one standard treatment in North America, is only regarded as a treatment
      option for patients after 'inadequate surgery' (i.e. <D2 dissection) in many
      European countries. 

PMID- 23867588
TI  - Overview of adjuvant and neoadjuvant therapy for resectable gastric cancer in the
      East.
AB  - This review presents the current status of adjuvant and neoadjuvant treatment
      options for primary resectable gastric cancer in the East, with updated data from
      recent studies. Marked disparities between the East and the West in standard
      surgical procedures (D2 vs. D1/0 lymphadenectomy) and their outcomes result in
      significant geographical variation in preferred adjuvant treatments. Currently,
      oral fluoropyrimidine-based postoperative adjuvant chemotherapy, 1 year of S-1
      chemotherapy, or capecitabine plus oxaliplatin for 6 months are the standards of
      care after curative resection with D2 lymphadenectomy for stage II/III gastric
      cancer in the East, though there is still some room for improvement. The role of
      postoperative adjuvant chemoradiotherapy (CRT) following curative D2 gastrectomy
      has long been debated in the East. However, the first prospective randomized
      controlled trial comparing CRT with chemotherapy alone failed to demonstrate a
      survival benefit, thus further studies are required. Chemotherapy has been
      pursued as a neoadjuvant approach in East Asia because of a rare locoregional
      recurrence after curative D2 gastrectomy. Locally advanced, marginally resectable
      gastric cancer with poor prognosis, such as large type 3 or 4 tumors, para-aortic
      and/or bulky nodal disease, and serosa-positive gastric cancer, is the main
      target of neoadjuvant chemotherapy. Promising efficacy has been demonstrated in
      several phase II studies with the safe use of D2 or more extended surgery
      following neoadjuvant chemotherapy. Although the results of ongoing phase III
      trials are awaited, Asian findings could be relevant and generalizable to other
      regions when D2 surgery is performed by experienced surgeons. 

PMID- 23867589
TI  - The new era of gastric cancer in the East and West: have our approaches
      harmonized?

PMID- 23867590
TI  - Laparoscopic gastrectomy for gastric cancer.
AB  - Laparoscopic gastrectomy for gastric cancer is rapidly becoming popular because
      of the technical developments and the accumulated data of laparoscopic surgery in
      gastric cancer patients. The aim of this review is to present the current body of
      evidence and to highlight controversial issues of laparoscopic gastrectomy for
      gastric cancer. Laparoscopic distal gastrectomy (LDG) provides better or
      comparable outcomes compared to conventional open distal gastrectomy (ODG) in
      terms of short-term results. The long-term survival of LDG is expected to be
      comparable to that of ODG in early-stage gastric cancer, and an ongoing Korean
      multicenter randomized controlled trial (KLASS-01) will provide more clear
      evidence. Laparoscopic total gastrectomy is still selectively performed compared
      to LDG, and there is still debate on the safety of the laparoscopic
      esophagojejunostomy technique. Laparoscopic pylorus-preserving gastrectomy seems
      to be preferred for early gastric cancer in the middle third of the stomach in
      terms of functional advantages and comparable oncologic outcome. Evidence for LDG
      for advanced gastric cancer is still insufficient and the issue of lack of
      generalization still remains, even after ongoing multicenter randomized
      controlled trials have revealed clinical evidence. Laparoscopic sentinel node
      navigation surgery is still experimental and the surgical procedure has yet to be
      standardized. Robotic gastrectomy is feasible for early gastric cancer in terms
      of similar outcome, but is much more expensive in comparison to laparoscopic
      surgery. Its benefit over the conventional laparoscopic gastrectomy has not yet
      been proven. 

PMID- 23867591
TI  - Gastric cancer staging with radiologic imaging modalities and UICC staging
      system.
AB  - There are two major stage classification systems for gastric cancer: the tumor
      node-metastasis (TNM) stages by the International Union against Cancer (UICC) and
      the Japanese Classification of Gastric Carcinoma by the Japanese Gastric Cancer
      Association (JGCA). Preoperative stage classification using either of these
      systems is essential for deciding on the treatment strategy in the era of various
      multimodal therapeutic options. Evolution of multidetector computerized
      tomography with isotropic volumetric imaging and various 3D images has increased
      the accuracy of T and N staging in patients with gastric cancer, although
      detection of peritoneal deposits and nodal metastasis in the absence of
      lymphadenopathy remain problematic with the imaging tools currently available.
      The TNM and JGCA classifications have undergone revisions independent of each
      other, and the discrepancies were not helpful when international comparisons and
      cooperation were needed. More recently, the JGCA and TNM classifications were
      merged to have identical T and N categories, in addition to the more
      straightforward M categories that indicate the presence of distant metastasis.
      The result of these efforts is that researchers in Japan and the rest of the
      world are now looking at a similar disease when they discuss cancer that belongs
      to the same stage. A nomogram that incorporates other established prognostic
      determinants in addition to the TNM component may be a future direction for a
      more sophisticated means of predicting outcome. The increasing incidence of
      junctional (esophagogastric junction) cancer in the Far East has spurred
      researchers from this region to adequately stage the disease and to consider
      suitable treatment modalities for this disease entity, whereas Western
      researchers are more inclined to treat this disease as esophageal cancer. This
      could be an area for future international debate. For the next more accurate
      staging, we suggest the collaboration between Eastern and Western high-volume
      centers in gastric cancer because the inconsistency of surgical approaches,
      especially with respect to nodal resection, remains a barrier to mutual
      understanding. 

PMID- 23867592
TI  - Gastric cancer pathology and underlying molecular mechanisms.
AB  - The development of gastric adenocarcinoma is a complex multistep process
      involving multiple genetic alterations. Based on pathology, four different
      macroscopic types and at least two major histological types, intestinal and
      diffuse, have been described. Most gastric cancer (GC) show genetic instability,
      either microsatellite instability or chromosomal instability, which is considered
      an early event in gastric carcinogenesis. Molecular studies of alterations of
      single genes have provided evidence that intestinal and diffuse type GC evolve
      via different genetic pathways. Recent results from high-throughput whole-genome
      expression or copy number studies have demonstrated extensive genetic diversity
      between cases and within individual GC. Sets of commonly up- or downregulated
      microRNAs have been identified in GC and might be useful in the near future to
      identify pathways of GC progression. Results from detailed molecular and/or
      pathological GC studies, although promising, still have limited clinical utility
      in predicting survival and stratifying GC patients for appropriate treatment. 

PMID- 23867593
TI  - Follow-up: the evidence.
AB  - There is currently no consensus on the best strategy for the follow-up of
      patients who have undergone surgical treatment with curative intent for gastric
      cancer. The wide variation in recommendations for surveillance among
      international experts and hospital schedules clearly reflects a lack of an
      established body of evidence on this subject. Consequently, most of the
      international guidelines aimed at early detection of disease recurrence gloss
      over details concerning the mode, duration, and intensity of surveillance since
      they cannot be based on an acceptable grade of recommendation. Very few report
      anything other than the detection of recurrences or death as the primary
      endpoints, and, given the poor survival of patients with recurrent gastric
      cancer, the prognostic effect of early detection seems doubtful. In recent years,
      an increasing focus on evidence-based medicine, which has coincided with a
      growing concern about costs and efficiency in medicine, has caused a reevaluation
      of most surveillance practices. In this paper, we review and discuss the current
      body of evidence and follow-up practices after curative resection of gastric
      cancer. 

PMID- 23867594
TI  - Treatment approaches to esophagogastric junction tumors.
AB  - Esophagogastric junction (EGJ) adenocarcinomas are usually classified into one of
      the three categories of the Siewert system. The clinicopathological features of
      EGJ adenocarcinomas vary according to this classification scheme. The lymphatic
      flow in EGJ tumors of any type is mainly toward the abdomen, and nodal metastasis
      to the upper or middle mediastinum from Siewert type II or III tumors is
      relatively uncommon. Thus, the transhiatal approach is regarded as the standard
      in surgery for Siewert type II or III tumors, while the transthoracic approach
      via a right thoracotomy is recommended for Siewert type I tumors.
      Chemoradiotherapy followed by surgery is regarded as the standard treatment for
      resectable cancer of the EGJ in Western countries, but the necessity of adding
      radiation therapy to preoperative chemotherapy remains unknown. In the East,
      postoperative adjuvant chemotherapy is the current standard of care since the
      survival benefit was proven in pivotal randomized trials for stage II/III gastric
      cancer, including adenocarcinoma of the EGJ. 

PMID- 23867595
TI  - Palliative treatment and the role of surgical resection in gastric cancer.
AB  - Adenocarcinoma of the stomach is often diagnosed in the late stages of the
      disease. Surgical resection of all gross and microscopic disease is essential for
      curative treatment. Complete resection is often not achievable when patients
      present with advanced stage IV cancer. In the absence of symptoms, chemotherapy
      without resection has been the standard of care in most major centers. With
      improvements in response to chemotherapy and less invasive surgical approaches,
      patients with metastatic gastric cancer have had better survival outcomes than in
      the past. The challenge today when treating these patients is in defining who
      will benefit from more aggressive interventions. Reviewing the literature for
      guidance is difficult because the goals of treatment are often not clearly
      defined. Finding the proper balance of aggressiveness needed to extend survival
      while preserving and maximizing quality of life is a decision that clinicians
      have to make with increasing frequency. This review will attempt to provide a
      framework to aid in determining what role, if any, gastrectomy has in the
      management of patients with stage IV gastric cancer. 

PMID- 23867596
TI  - Characterization of acute heart failure hospitalizations in a Portuguese
      cardiology department.
AB  - INTRODUCTION AND AIMS: We describe the clinical characteristics, management and
      outcomes of patients hospitalized with acute heart failure in a south-west
      European cardiology department. We sought to identify the determinants of length
      of stay and heart failure rehospitalization or death during a 12-month follow-up
      period. METHODS AND RESULTS: This was a retrospective cohort study including all
      patients admitted during 2010 with a primary or secondary diagnosis of acute
      heart failure. Death and readmission were followed through 2011. Of the 924
      patients admitted, 201 (21%) had acute heart failure, 107 (53%) of whom had new
      onset acute heart failure. The main precipitating factors were acute coronary
      syndrome (63%) and arrhythmia (14%). The most frequent clinical presentations
      were heart failure after acute coronary syndrome (63%), chronic decompensated
      heart failure (47%) and acute pulmonary edema (21%). On admission 73% had left
      ventricular ejection fraction <50%. Median length of stay was 11 days and in
      hospital mortality was 5.5%. The rehospitalization rate was 21% and 24% at six
      and 12 months, respectively. All-cause mortality was 16% at 12 months. The
      independent predictors of rehospitalization or death were heart failure
      hospitalization during the previous year (Hazard ratio - HR - 3.177), serum
      sodium <135mmol/l on admission (HR 1.995) and atrial fibrillation (HR 1.791).
      Reduced left ventricular ejection fraction was associated with a lower risk of
      rehospitalization or death (HR 0.518). CONCLUSIONS: Our patients more often
      presented new-onset acute heart failure, due to an acute coronary syndrome, with
      reduced left ventricular ejection fraction. Several predictive factors of death
      or rehospitalization were identified that may help to select high-risk patients
      to be followed in a heart failure management program after discharge.

PMID- 23867597
TI  - Correlation between imaging and molecular classification of breast cancers.
AB  - The histological type of tumour according to the WHO: ductal, lobular, rare
      forms, is correlated with specific aspects of the imaging based on each type.
      This morphological classification was improved by knowledge of the molecular
      anomalies of breast cancers, resulting in the definition of cancer sub-groups
      with distinct prognoses and different responses to treatment: luminal A, luminal
      B, HER2 positive, basal-like, triple-negative. Studies are beginning to deal with
      the appearance of each sub-type in the imaging. It is now important for the
      radiologist to be familiar with them. 

PMID- 23867598
TI  - Histological examination of the human obliquus capitis inferior myodural bridge.
AB  - This study was designed to examine the anatomical relationship between the
      obliquus capitis inferior (OCI) muscle and the cervical dura mater at the
      histological level. Eight human cadavers, with an average age of 65 +/- 7.9 years
      were selected from a convenience sample for suboccipital dissection. Twelve OCI
      muscle specimens were excised, 100% of which emitted grossly visible soft tissue
      tracts that inserted into the posterolateral aspect of the cervical dura. These
      12 myodural specimens were excised as single, continuous structures and sent for
      H&E staining. One sample also underwent immuno-peroxidase staining. Microscopic
      evaluation confirmed a connective tissue bridge emanating from the OCI muscular
      body and attaching to the posterolateral aspect of the cervical dura mater in 75%
      of the specimens. Microtome slices of the remaining 25% were not able to capture
      muscle, connective tissue and dura within the same plane and were therefore
      unable to be properly analyzed. The sample sent for neuro-analysis stained
      positively for several neuronal fascicles traveling within, and passing through
      the OCI myodural bridge. This study histologically confirms the presence of a
      connective tissue bridge that links the OCI muscle to the dura mater and the
      presence of neuronal tissue within this connection warrants further examination.
      This structure may represent a component of normal human anatomy. In addition to
      its hypothetical role in human homeostasis, it may contribute to certain
      neuropathological conditions, as well.

PMID- 23867599
TI  - Genome-wide analysis and identification of stress-responsive genes of the NAM
      ATAF1,2-CUC2 transcription factor family in apple.
AB  - NAC (NAM, ATAF1,2, and CUC2) proteins constitute one of the largest families of
      plant-specific transcription factors. To date, little is known about the NAC
      genes in the apple (Malus domestica). In this study, a total of 180 NAC genes
      were identified in the apple genome and were phylogenetically clustered into six
      groups (I-VI) with the NAC genes from Arabidopsis and rice. The predicted apple
      NAC genes were distributed across all of 17 chromosomes at various densities.
      Additionally, the gene structure and motif compositions of the apple NAC genes
      were analyzed. Moreover, the expression of 29 selected apple NAC genes was
      analyzed in different tissues and under different abiotic stress conditions. All
      of the selected genes, with the exception of four genes, were expressed in at
      least one of the tissues tested, which indicates that the NAC genes are involved
      in various aspects of the physiological and developmental processes of the apple.
      Encouragingly, 17 of the selected genes were found to respond to one or more of
      the abiotic stress treatments, and these 17 genes included not only the expected
      7 genes that were clustered with the well-known stress-related marker genes in
      group IV but also 10 genes located in other subgroups, none of which contains
      members that have been reported to be stress-related. To the best of our
      knowledge, this report describes the first genome-wide analysis of the apple NAC
      gene family, and the results should provide valuable information for
      understanding the classification and putative functions of this family. 

PMID- 23867600
TI  - Overexpression of GsZFP1 enhances salt and drought tolerance in transgenic
      alfalfa (Medicago sativa L.).
AB  - GsZFP1 encodes a Cys2/His2-type zinc-finger protein. In our previous study, when
      GsZFP1 was heterologously expressed in Arabidopsis, the transgenic Arabidopsis
      plants exhibited enhanced drought and cold tolerance. However, it is still
      unknown whether GsZFP1 is also involved in salt stress. GsZFP1 is from the wild
      legume Glycine soja. Therefore, the aims of this study were to further elucidate
      the functions of the GsZFP1 gene under salt and drought stress in the forage
      legume alfalfa and to investigate its biochemical and physiological functions
      under these stress conditions. Our data showed that overexpression of GsZFP1 in
      alfalfa resulted in enhanced salt tolerance. Under high salinity stress, greater
      relative membrane permeability and malondialdehyde (MDA) content were observed
      and more free proline and soluble sugars accumulated in transgenic alfalfa than
      in the wild-type (WT) plants; in addition, the transgenic lines accumulated less
      Na(+) and more K(+) in both the shoots and roots. Overexpression of GsZFP1 also
      enhanced the drought tolerance of alfalfa. The fold-inductions of stress
      responsive marker gene expression, including MtCOR47, MtRAB18, MtP5CS, and MtRD2,
      were greater in transgenic alfalfa than those of WT under drought stress
      conditions. In conclusion, the transgenic alfalfa plants generated in this study
      could be used for farming in salt-affected as well as arid and semi-arid areas. 

PMID- 23867601
TI  - RNAi based simultaneous silencing of all forms of light-dependent
      NADPH:protochlorophyllide oxidoreductase genes result in the accumulation of
      protochlorophyllide in tobacco (Nicotiana tabacum).
AB  - Conversion of protochlorophyllide (Pchlide) into chlorophyllide (Chlide), a key
      step in chlorophyll biosynthesis, is mediated by a light-dependent
      NADPH:protochlorophyllide oxidoreductase (POR). POR exists in multiple isoforms
      that share high degree of homology. RNAi-mediated gene silencing approach was
      used to suppress the expression of POR genes in order to study its role in the
      Chls biosynthesis in tobacco (Nicotiana tabacum L.). The transgenic plants were
      devoid of chlorophyll pigments and resembled albino plants. Northern blot
      analysis confirmed the degradation of POR transcripts into 21-23 bp fragments.
      Pigment analysis showed the accumulation of various intermediate compounds of Chl
      biosynthesis pathway including Pchlide. However, no trace of chlorophyll was
      observed. As compared to wild type, POR-silenced plants accumulated larger (60%)
      amounts of Pchlide from its endogenous substrate. When leaf discs of WT and POR
      silenced plants were treated with exogenous ALA both WT and POR-silenced plants
      accumulated large amounts of tetrapyrrolic intermediates demonstrating that
      Pchlide biosynthesis potential was not suppressed in POR-silenced plants. Upon
      illumination, WT plants photo-transformed large amounts of Pchlide to Chlide.
      However, POR-silenced plants almost completely failed to do so. Results
      demonstrate that the antisense approaches to drop expression of individual POR
      isoforms have provided valuable insights into the role of distinct PORs during
      greening. Moreover, data illustrate that the POR is the only enzyme that can
      convert the Pchlide to Chlide and there is no alternate enzyme that can
      substitute the POR in higher plants. Thus, this investigation describes ideal
      mechanism for the silencing of POR isozymes in tobacco.

PMID- 23867603
TI  - Synthesis of 3'-azido-2',3'-dideoxy-5-fluorouridine phosphoramidates and
      evaluation of their anticancer activity.
AB  - A series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3'-azido-2',3'
      dideoxy-5-fluorouridine (12-21) were synthesized by means of phosphorylation of
      3'-azido-2',3'-dideoxy-5-fluorouridine (4) with 4-chlorophenyl
      phosphoroditriazolide (10) followed by a reaction with the appropriate amine. The
      synthesized phosphoramidates (12-21) were evaluated for their cytotoxic activity
      in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7)
      using the sulforhodamine B (SRB) assay. The highest activity in all the
      investigated cancer cells was displayed by phosphoramidate 13 with the N-ethyl
      substituent and its activity was much higher than that of the parent nucleoside.
      Also phosphoramidate 17 with the N-propargyl substituent exhibited good activity
      in all the used cell lines. 

PMID- 23867602
TI  - Lead identification of novel and selective TYK2 inhibitors.
AB  - A therapeutic rationale is proposed for the treatment of inflammatory diseases,
      such as psoriasis and inflammatory bowel diseases (IBD), by selective targeting
      of TYK2. Hit triage, following a high-throughput screen for TYK2 inhibitors,
      revealed pyridine 1 as a promising starting point for lead identification.
      Initial expansion of 3 separate regions of the molecule led to eventual
      identification of cyclopropyl amide 46, a potent lead analog with good kinase
      selectivity, physicochemical properties, and pharmacokinetic profile. Analysis of
      the binding modes of the series in TYK2 and JAK2 crystal structures revealed key
      interactions leading to good TYK2 potency and design options for future
      optimization of selectivity. 

PMID- 23867604
TI  - N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines: a novel class of antitumor agents
      targeting the colchicine site on tubulin.
AB  - Structural optimizations of the prior lead 1a led to the discovery of a series of
      N-aryl-6-methoxy-1,2,3,4-tetrahydroquinoline derivatives as a novel class of
      tubulin polymerization inhibitors targeted at the colchicine binding site. The
      most active compound 6d showed extremely high cytotoxicity against a human tumor
      cell line panel (A549, KB, KBvin, and DU145) with GI50 values ranging from 1.5 to
      1.7 nM, significantly more potent than paclitaxel, especially against the drug
      resistant KBvin cell line, in the same assays. Analogs 5f, 6b, 6c, and 6e were
      also quite potent, with a GI50 range of 0.011-0.19 MUM. In further studies,
      active compounds 6b-e and 5f significantly inhibited tubulin assembly, with IC50
      values of 0.92-1.0 MUM and strongly inhibited colchicine binding to tubulin, with
      inhibition rates of 75-99% (at 5 MUM), comparable with or more potent than
      combretastatin A-4 (IC50 0.96 MUM). Current studies included design, synthesis,
      and biological evaluations of 24 new compounds (series 3-6). Related SAR
      analysis, molecular modeling, and evaluation of essential drug-like properties,
      i.e. water solubility, log P, and in vitro metabolic stability, were also
      performed. 

PMID- 23867605
TI  - Discovery of the first inhibitors of bacterial enzyme D-aspartate ligase from
      Enterococcus faecium (Aslfm).
AB  - The D-aspartate ligase of Enterococcus faecium (Aslfm) is an attractive target
      for the development of narrow-spectrum antibacterial agents that are active
      against multidrug-resistant E. faecium. Although there is currently little
      available information regarding the structural characteristics of Aslfm, we
      exploited the knowledge that this enzyme belongs to the ATP-grasp superfamily to
      target its ATP binding site. In the first design stage, we synthesized and
      screened a small library of known ATP-competitive inhibitors of ATP-grasp
      enzymes. A series of amino-oxazoles derived from bacterial biotin carboxylase
      inhibitors showed low micromolar activity. The most potent inhibitor compound 12,
      inhibits Aslfm with a Ki value of 2.9 MUM. In the second design stage, a
      validated ligand-based pharmacophore modeling approach was used, taking the newly
      available inhibition data of an initial series of compounds into account.
      Experimental evaluation of the virtual screening hits identified two novel
      structural types of Aslfm inhibitors with 7-amino-9H-purine (18) and 7-amino-1H
      pyrazolo[3,4-d]pyrimidine (30 and 34) scaffolds, and also with Ki values in the
      low micromolar range. Investigation the inhibitors modes of action confirmed that
      these compounds are competitive with respect to the ATP molecule. The binding of
      inhibitors to the target enzyme was also studied using isothermal titration
      calorimetry (ITC). Compounds 6, 12, 18, 30 and 34 represent the first inhibitors
      of Aslfm reported to date, and are an important step forward in combating
      infections due to E. faecium.

PMID- 23867606
TI  - Structure prediction of partial-length protein sequences.
AB  - Protein structure information is essential to understand protein function.
      Computational methods to accurately predict protein structure from the sequence
      have primarily been evaluated on protein sequences representing full-length
      native proteins. Here, we demonstrate that top-performing structure prediction
      methods can accurately predict the partial structures of proteins encoded by
      sequences that contain approximately 50% or more of the full-length protein
      sequence. We hypothesize that structure prediction may be useful for predicting
      functions of proteins whose corresponding genes are mapped expressed sequence
      tags (ESTs) that encode partial-length amino acid sequences. Additionally, we
      identify a confidence score representing the quality of a predicted structure as
      a useful means of predicting the likelihood that an arbitrary polypeptide
      sequence represents a portion of a foldable protein sequence ("foldability").
      This work has ramifications for the prediction of protein structure with limited
      or noisy sequence information, as well as genome annotation. 

PMID- 23867607
TI  - Proteolytic cleavage of apolipoprotein E4 as the keystone for the heightened risk
      associated with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized
      by microscopic lesions consisting of beta-amyloid plaques and neurofibrillary
      tangles (NFTs). The majority of cases are defined as sporadic and are likely
      caused by a combination of both genetic and environmental factors. Of the genetic
      risk factors identified, the 34 kDa protein, apolipoprotein (apo) E4, is of
      significant importance as APOE4 carriers account for 65%-80% of all AD cases.
      Although apoE4 plays a normal role in lipoprotein transport, how it contributes
      to AD pathogenesis is currently unknown. One potential mechanism by which apoE4
      contributes to disease risk is its propensity to undergo proteolytic cleavage
      generating N- and C-terminal fragments. The purpose of this review will be to
      examine the mechanisms by which apoE4 contributes to AD pathogenesis focusing on
      the potential loss or gain of function that may occur following cleavage of the
      full-length protein. In this context, a discussion of whether targeting apoE4
      therapeutically is a rationale approach to treating this disease will be
      assessed. 

PMID- 23867608
TI  - SnoRNA U50 levels are regulated by cell proliferation and rRNA transcription.
AB  - rRNA post transcriptional modifications play a role in cancer development by
      affecting ribosomal function. In particular, the snoRNA U50, mediating the
      methylation of C2848 in 28S rRNA, has been suggested as a potential tumor
      suppressor-like gene playing a role in breast and prostate cancers and B-cell
      lymphoma. Indeed, we observed the downregulation of U50 in colon cancer cell
      lines as well as tumors. We then investigated the relationship between U50 and
      proliferation in lymphocytes stimulated by phytohemagglutinin (PHA) and observed
      a strong decrease in U50 levels associated with a reduced C2848 methylation. This
      reduction was due to an alteration of U50 stability and to an increase of its
      consumption. Indeed, the blockade of ribosome biogenesis induced only an early
      decrease in U50 followed by a stabilization of U50 levels when ribosome
      biogenesis was almost completely blocked. Similar results were found with other
      snoRNAs. Lastly, we observed that U50 modulation affects ribosome efficiency in
      IRES-mediated translation, demonstrating that changes in the methylation levels
      of a single specific site on 28S rRNA may alter ribosome function. In conclusion,
      our results link U50 to the cellular proliferation rate and ribosome biogenesis
      and these findings may explain why its levels are often greatly reduced in
      cancers. 

PMID- 23867609
TI  - Identification and expression profile analysis of odorant binding proteins in the
      oriental fruit fly Bactrocera dorsalis.
AB  - Olfaction is crucial in many insects for critical behaviors, including those
      regulating survival and reproduction. Insect odorant-binding proteins (OBPs)
      function in the first step of the olfactory system and play an essential role in
      the perception of odorants, such as pheromones and host chemicals. The oriental
      fruit fly, Bactrocera dorsalis, is a destructive fruit-eating pest, due to its
      wide host range of up to 250 different types of fruits and vegetables, and this
      fly causes severe economic damage to the fruit and vegetable industry. However,
      OBP genes have not been largely identified in B. dorsalis. Based on our
      previously constructed B. dorsalis cDNA library, ten OBP genes were identified in
      B. dorsalis for the first time. A phylogenetic tree was generated to show the
      relationships among the 10 OBPs of B. dorsalis to OBP sequences of two other
      Dipteran species, including Drosophila melanogaster and the mosquito Anopheles
      gambiae. The expression profiles of the ten OBPs in different tissues (heads,
      thoraxes, abdomens, legs, wings, male antennae and female antenna) of the mated
      adults were analyzed by real-time PCR. The results showed that nine of them are
      highly expressed in the antenna of both sexes, except BdorOBP7. Four OBPs
      (BdorOBP1, BdorOBP4, BdorOBP8, and BdorOBP10) are also enriched in the abdomen,
      and BdorOBP7 is specifically expressed in leg, indicating that it may function in
      other biological processes. This work will provide insight into the roles of OBPs
      in chemoreception and help develop new pest-control strategies. 

PMID- 23867610
TI  - Plant flavonoids--biosynthesis, transport and involvement in stress responses.
AB  - This paper aims at analysing the synthesis of flavonoids, their import and export
      in plant cell compartments, as well as their involvement in the response to
      stress, with particular reference to grapevine (Vitis vinifera L.). A multidrug
      and toxic compound extrusion (MATE) as well as ABC transporters have been
      demonstrated in the tonoplast of grape berry, where they perform a flavonoid
      transport. The involvement of a glutathione S-transferase (GST) gene has also
      been inferred. Recently, a putative flavonoid carrier, similar to mammalian
      bilitranslocase (BTL), has been identified in both grape berry skin and pulp. In
      skin the pattern of BTL expression increases from veraison to harvest, while in
      the pulp its expression reaches the maximum at the early ripening stage.
      Moreover, the presence of BTL in vascular bundles suggests its participation in
      long distance transport of flavonoids. In addition, the presence of a vesicular
      trafficking in plants responsible for flavonoid transport is discussed. Finally,
      the involvement of flavonoids in the response to stress is described. 

PMID- 23867612
TI  - Interleukin-10 prevents epithelial cell apoptosis by regulating IFNgamma and
      TNFalpha expression in rhesus macaque colon explants.
AB  - Interleukin-10 (IL-10) is an important immunomodulatory cytokine that plays an
      obligate role in regulating inflammatory responses. Here we demonstrated the role
      of IL-10 in regulating crypts length and breadth as well as maintaining the
      survival of epithelial cells using rhesus colon explant cultures. Anti-IL-10
      antibody treatment of colon explant cultures induced increased production of
      inflammatory cytokines/molecules like IFNgamma, TNFalpha, CD107a and perforin as
      well as increased epithelial cell apoptosis compared to media controls tested.
      Our results suggest that IL-10 plays a crucial role in maintaining mucosal
      homeostasis by regulating mucosal IFNgamma and TNFalpha cytokine production.

PMID- 23867611
TI  - Could radiotherapy effectiveness be enhanced by electromagnetic field treatment?
AB  - One of the main goals in radiobiology research is to enhance radiotherapy
      effectiveness without provoking any increase in toxicity. In this context, it has
      been proposed that electromagnetic fields (EMFs), known to be modulators of
      proliferation rate, enhancers of apoptosis and inductors of genotoxicity, might
      control tumor recruitment and, thus, provide therapeutic benefits. Scientific
      evidence shows that the effects of ionizing radiation on cellular compartments
      and functions are strengthened by EMF. Although little is known about the
      potential role of EMFs in radiotherapy (RT), the radiosensitizing effect of EMFs
      described in the literature could support their use to improve radiation
      effectiveness. Thus, we hypothesized that EMF exposure might enhance the ionizing
      radiation effect on tumor cells, improving the effects of RT. The aim of this
      paper is to review reports of the effects of EMFs in biological systems and their
      potential therapeutic benefits in radiotherapy. 

PMID- 23867613
TI  - [Formal quality assessment of informed consent documents in 9 hospitals].
AB  - INTRODUCTION: Informed consent forms are very important in the process of medical
      information. The aim of this study is to design reliable formal quality criteria
      of these documents and their application in the evaluation of those used in the
      hospitals of a regional health service. MATERIAL AND METHODS: Criteria have been
      designed from the analysis of existing regulations, previous studies and
      consultation with key experts. The interobserver concordance was assessed using
      the kappa index. Criteria evaluation was performed on 1425 documents of 9
      hospitals. RESULTS: A total of 19 criteria used in the evaluation of the quality
      of informed consent forms have been obtained. Kappa values were higher than 0,60
      in 17 of them and higher than 0,52 in the other 2. The average number of defects
      per document was 7.6, with a high-low ratio among hospitals of 1.84. More than
      90% of the documents had defects in the information on consequences and
      contraindications, and in about 90% it did not mention the copy to the patient.
      More than 60% did not comply with stating the purpose of the procedure, a
      statement of having understood and clarified doubts, and the treatment options.
      CONCLUSIONS: A tool has been obtained to reliably assess the formal quality of
      the informed consent forms. The documents assessed have a wide margin for
      improvement related to giving a copy to the patient, and some aspects of the
      specific information that patients should receive.

PMID- 23867614
TI  - [Impact of short-stay units on the quality of medical care in Spain].
AB  - OBJECTIVE: Short-stay units (SSUs) have been developed as an alternative to
      conventional hospitalisation. The aim of this study is to analyse the impact of
      short-stay units on the quality of medical care in Spain. MATERIAL AND METHODS: A
      systematic review was performed by retrieving studies that analysed the results
      of SSUs in Spain, in terms of clinical effectiveness, efficiency and satisfaction
      among patients, using an electronic database search (Pubmed/Medline and Spanish
      Medical Index) and a review of selected references. The data collected included,
      mortality, length of stay and re-admission rates, as well as other variables.
      RESULTS: Twenty-seven articles were found, with a great heterogeneity in both
      study design and type of SSU analysed. After analysing results, it was observed
      that SSUs in Spain provided effective clinical care. Low-quality evidence was
      also found supporting the hypothesis that SSUs are able to reduce overall length
      of stay in the whole hospital or department where they were created. There are
      not enough data to support any other advantages or benefits of SSUs, when
      compared with other hospitalisation units. CONCLUSIONS: SSUs may be able to
      effectively improve clinical care in selected patients, and may help to shorten
      overall length of stay. Further research is needed in order to define their exact
      role and to establish their optimal model.

PMID- 23867615
TI  - [Short-stay medical units].

PMID- 23867616
TI  - An investigation of volatile organic compounds from the saliva of healthy
      individuals using headspace-trap/GC-MS.
AB  - Analysis of volatile organic compounds (VOCs) from saliva, to aid disease
      diagnoses, has received little attention. This work aims to address the paucity
      of information on saliva volatiles and includes a database of newly identified
      compounds whilst incorporating a review of the literature. The volatile
      constituents in the headspace of whole saliva obtained from ten healthy
      individuals were examined in a longitudinal study over a period of ten days using
      headspace-trap gas chromatography-mass spectrometry (HS-trap/GC-MS). A total of
      317 compounds (268 identified) were found and compared across subjects and
      between samples with 34 VOCs being present in all 100 samples. The average number
      of compounds per subject ranged from 121 to 150 over a 10 day period and was
      fairly consistent for a particular individual (s.d. ranged from 3-15). However,
      the number of compounds present in an individual on all ten days was
      substantially lower ranging between 65 and 109, showing that there is significant
      daily variation in salivary composition. A core group of ubiquitous VOCs were
      found with the remaining VOCs showing significant intra and inter individual
      variability. Saliva VOCs have been found to be readily analysed using the HS-trap
      technique and studies on the VOCs from healthy individuals should be of utility
      for comparison with VOCs analysed from samples from diseased groups. 

PMID- 23867617
TI  - New treatment option: 223Ra chloride, the first approved unsealed alpha-emitting
      radiopharmaceutical.
AB  - A 66-year-old man with prostate cancer presented with intractable pain associated
      with multifocal bone metastases. After receiving 180 uCi (1.35 uCi/kg) of (223)Ra
      chloride, radiation survey measured 0.2 mR/h at 1 m, and the patient was
      discharged to home. He will return monthly for the next 5 months for repeat
      (223)Ra chloride administrations. (223)Ra chloride is the first Food and Drug
      Administration-approved unsealed alpha-emitting radiopharmaceutical.

PMID- 23867618
TI  - Imaging of bronchioloalveolar carcinoma in the mice with the alphaVbeta3 integrin
      targeted tracer (99m)Tc-RGD-4CK.
AB  - Receptor-based imaging agents have shown improved specificity and sensitivity of
      cancer diagnosis by targeting the specific features of cancer. Here we reported
      the (99m)Tc-labeling of a cyclic polypeptide RGD-4CK and the characterization of
      this agent in vitro and in bronchioloalveolar carcinoma (BAC) xenograft model.
      The alphaVbeta3 integrin receptor binding affinity of (99m)Tc-RGD-4CK was
      determined in BAC. The cancer targeting properties of (99m)Tc-RGD-4CK were
      determined in NCI-H358 xenografted nude mice. Moreover, the BAC uptake of (99m)Tc
      RGD-4CK was blocked with nonradiolabeled RGD-4CK in xenografts. The competitive
      assay showed that (99m)Tc-RGD-4CK exhibited high specificity to BAC cell line NCI
      H358. Biodistribution studies indicated that (99m)Tc-RGD-4CK exhibited high tumor
      uptake (4.12 +/- 1.21% injected dose/g 120 minutes after injection) and prolonged
      tumor retention (2.08 +/- 0.33% injected dose/g 240 minutes after injection) in
      NCI-H358 xenografted nude mice. Moreover, (99m)Tc-RGD-4CK produced a good tumor
      to-lung ratio (2.38) because of low lung activity accumulation 120 minutes
      postinjection. BAC on the flank of xenografted mice was clearly visualized by
      single photon emission computed tomography/computed tomography imaging using
      (99m)Tc-RGD-4CK. In conclusion, this study provides evidence that (99m)Tc-RGD-4CK
      is a promising agent for noninvasive determination of alphaVbeta3 integrin status
      and therapy monitoring in BAC.

PMID- 23867619
TI  - A link between FTO, ghrelin, and impaired brain food-cue responsivity.
AB  - Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated
      with human obesity and obesity-prone behaviors, including increased food intake
      and a preference for energy-dense foods. FTO demethylates N6-methyladenosine, a
      potential regulatory RNA modification, but the mechanisms by which FTO
      predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight
      humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A
      allele have dysregulated circulating levels of the orexigenic hormone acyl
      ghrelin and attenuated postprandial appetite reduction. Using functional MRI
      (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype
      modulates the neural responses to food images in homeostatic and brain reward
      regions. Furthermore, AA and TT subjects exhibited divergent neural
      responsiveness to circulating acyl-ghrelin within brain regions that regulate
      appetite, reward processing, and incentive motivation. In cell models, FTO
      overexpression reduced ghrelin mRNA N6-methyladenosine methylation, concomitantly
      increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells
      from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N6
      methyladenosine methylation, and increased ghrelin mRNA abundance compared with
      TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of
      ingestive behavior, and offer insight into how FTO obesity-risk alleles
      predispose to increased energy intake and obesity in humans. 

PMID- 23867621
TI  - Cerebrovascular degradation of TRKB by MMP9 in the diabetic brain.
AB  - Diabetes elevates the risk for neurological diseases, but little is known about
      the underlying mechanisms. Brain-derived neurotrophic factor (BDNF) is secreted
      by microvascular endothelial cells (ECs) in the brain, functioning as a
      neuroprotectant through the activation of the neurotrophic tyrosine kinase
      receptor TRKB. In a rat model of streptozotocin-induced hyperglycemia, we found
      that endothelial activation of MMP9 altered TRKB-dependent trophic pathways by
      degrading TRKB in neurons. Treatment of brain microvascular ECs with advanced
      glycation endproducts (AGE), a metabolite commonly elevated in diabetic patients,
      increased MMP9 activation, similar to in vivo findings. Recombinant human MMP9
      degraded the TRKB ectodomain in primary neuronal cultures, suggesting that TRKB
      could be a substrate for MMP9 proteolysis. Consequently, AGE-conditioned
      endothelial media with elevated MMP9 activity degraded the TRKB ectodomain and
      simultaneously disrupted the ability of endothelium to protect neurons against
      hypoxic injury. Our findings demonstrate that neuronal TRKB trophic function is
      ablated by MMP9-mediated degradation in the diabetic brain, disrupting
      cerebrovascular trophic coupling and leaving the brain vulnerable to injury. 

PMID- 23867620
TI  - Medullary thymic epithelial cell depletion leads to autoimmune hepatitis.
AB  - TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance
      by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate
      T cell tolerance by ectopically expressing self-antigens and eliminating
      autoreactive T cells in the thymus. Here we show that mice with mTEC depletion
      due to conditional deletion of Traf6 expression in murine thymic epithelial cells
      (Traf6DeltaTEC mice) showed a surprisingly narrow spectrum of autoimmunity
      affecting the liver. The liver inflammation in Traf6DeltaTEC mice exhibited all
      the histological and immunological characteristics of human autoimmune hepatitis
      (AIH). The role of T cells in AIH establishment was supported by intrahepatic T
      cell population changes and AIH development after transfer of liver T cells into
      immunodeficient mice. Despite a 50% reduction in natural Treg thymic output,
      peripheral tolerance in Traf6DeltaTEC mice was normal, whereas compensatory T
      regulatory mechanisms were evident in the liver of these animals. These data
      indicate that mTECs exert a cell-autonomous role in central T cell tolerance and
      organ-specific autoimmunity, but play a redundant role in peripheral tolerance.
      These findings also demonstrate that Traf6DeltaTEC mice are a relevant model with
      which to study the pathophysiology of AIH, as well as autoantigen-specific T cell
      responses and regulatory mechanisms underlying this disease. 

PMID- 23867622
TI  - Recruited brown adipose tissue as an antiobesity agent in humans.
AB  - Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to
      cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron
      emission tomography and computed tomography, we previously reported that BAT
      decreases with age and thereby accelerates age-related accumulation of body fat
      in humans. Thus, the recruitment of BAT may be effective for body fat reduction.
      In this study, we examined the effects of repeated stimulation by cold and
      capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT
      activity. Acute cold exposure at 19 degrees C for 2 hours increased energy
      expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with
      BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure
      at 17 degrees C for 6 weeks resulted in a parallel increase in BAT activity and
      CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body
      fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for
      6 weeks increased CIT. These results demonstrate that human BAT can be recruited
      even in individuals with decreased BAT activity, thereby contributing to body fat
      reduction. 

PMID- 23867623
TI  - Atrial natriuretic peptide is negatively regulated by microRNA-425.
AB  - Numerous common genetic variants have been linked to blood pressure, but no
      underlying mechanism has been elucidated. Population studies have revealed that
      the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding
      atrial natriuretic peptide (ANP), is associated with blood pressure. We selected
      individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or
      high-salt diet for 1 week, after which they were challenged with an intravenous
      saline infusion. On both diets, before and after saline administration, ANP
      levels were up to 50% higher in AG individuals than in AA individuals, a
      difference comparable to the changes induced by high-salt diet or saline
      infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068
      genotype. We identified a microRNA, miR-425, that is expressed in human atria and
      ventricles and is predicted to bind the sequence spanning rs5068 for the A, but
      not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with
      the G allele conferring resistance to miR-425. This study identifies miR-425 as a
      regulator of ANP production, raising the possibility that miR-425 antagonists
      could be used to treat disorders of salt overload, including hypertension and
      heart failure. 

PMID- 23867624
TI  - FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary
      hypertension.
AB  - Dysfunctional bone morphogenetic protein receptor-2 (BMPR2) signaling is
      implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We used
      a transcriptional high-throughput luciferase reporter assay to screen 3,756 FDA
      approved drugs and bioactive compounds for induction of BMPR2 signaling. The best
      response was achieved with FK506 (tacrolimus), via a dual mechanism of action as
      a calcineurin inhibitor that also binds FK-binding protein-12 (FKBP12), a
      repressor of BMP signaling. FK506 released FKBP12 from type I receptors activin
      receptor-like kinase 1 (ALK1), ALK2, and ALK3 and activated downstream SMAD1/5
      and MAPK signaling and ID1 gene regulation in a manner superior to the
      calcineurin inhibitor cyclosporine and the FKBP12 ligand rapamycin. In pulmonary
      artery endothelial cells (ECs) from patients with idiopathic PAH, low-dose FK506
      reversed dysfunctional BMPR2 signaling. In mice with conditional Bmpr2 deletion
      in ECs, low-dose FK506 prevented exaggerated chronic hypoxic PAH associated with
      induction of EC targets of BMP signaling, such as apelin. Low-dose FK506 also
      reversed severe PAH in rats with medial hypertrophy following monocrotaline and
      in rats with neointima formation following VEGF receptor blockade and chronic
      hypoxia. Our studies indicate that low-dose FK506 could be useful in the
      treatment of PAH. 

PMID- 23867625
TI  - FOXOs attenuate bone formation by suppressing Wnt signaling.
AB  - Wnt/beta-catenin/TCF signaling stimulates bone formation and suppresses
      adipogenesis. The hallmarks of skeletal involution with age, on the other hand,
      are decreased bone formation and increased bone marrow adiposity. These changes
      are associated with increased oxidative stress and decreased growth factor
      production, which activate members of the FOXO family of transcription factors.
      FOXOs in turn attenuate Wnt/beta-catenin signaling by diverting beta-catenin from
      TCF- to FOXO-mediated transcription. We show herein that mice lacking Foxo1, -3,
      and -4 in bipotential progenitors of osteoblast and adipocytes (expressing
      Osterix1) exhibited increased osteoblast number and high bone mass that was
      maintained in old age as well as decreased adiposity in the aged bone marrow. The
      increased bone mass in the Foxo-deficient mice was accounted for by increased
      proliferation of osteoprogenitor cells and bone formation resulting from
      upregulation of Wnt/beta-catenin signaling and cyclin D1 expression, but not
      changes in redox balance. Consistent with this mechanism, beta-catenin deletion
      in Foxo null cells abrogated both the increased cyclin D1 expression and
      proliferation. The elucidation of a restraining effect of FOXOs on Wnt signaling
      in bipotential progenitors suggests that FOXO activation by accumulation of age
      associated cellular stressors may be a seminal pathogenetic mechanism in the
      development of involutional osteoporosis. 

PMID- 23867626
TI  - Cold acclimation recruits human brown fat and increases nonshivering
      thermogenesis.
AB  - In recent years, it has been shown that humans have active brown adipose tissue
      (BAT) depots, raising the question of whether activation and recruitment of BAT
      can be a target to counterbalance the current obesity pandemic. Here, we show
      that a 10-day cold acclimation protocol in humans increases BAT activity in
      parallel with an increase in nonshivering thermogenesis (NST). No sex differences
      in BAT presence and activity were found either before or after cold acclimation.
      Respiration measurements in permeabilized fibers and isolated mitochondria
      revealed no significant contribution of skeletal muscle mitochondrial uncoupling
      to the increased NST. Based on cell-specific markers and on uncoupling protein-1
      (characteristic of both BAT and beige/brite cells), this study did not show
      "browning" of abdominal subcutaneous white adipose tissue upon cold acclimation.
      The observed physiological acclimation is in line with the subjective changes in
      temperature sensation; upon cold acclimation, the subjects judged the environment
      warmer, felt more comfortable in the cold, and reported less shivering. The
      combined results suggest that a variable indoor environment with frequent cold
      exposures might be an acceptable and economic manner to increase energy
      expenditure and may contribute to counteracting the current obesity epidemic. 

PMID- 23867627
TI  - Structural insights into substrate recognition in proton-dependent oligopeptide
      transporters.
AB  - Short-chain peptides are transported across membranes through promiscuous proton
      dependent oligopeptide transporters (POTs)--a subfamily of the major facilitator
      superfamily (MFS). The human POTs, PEPT1 and PEPT2, are also involved in the
      absorption of various drugs in the gut as well as transport to target cells.
      Here, we present a structure of an oligomeric POT transporter from Shewanella
      oneidensis (PepTSo2), which was crystallized in the inward open conformation in
      complex with the peptidomimetic alafosfalin. All ligand-binding residues are
      highly conserved and the structural insights presented here are therefore likely
      to also apply to human POTs.

PMID- 23867628
TI  - Walking or dancing: patterns of physical activity by cross-sectional age among
      U.S. women.
AB  - OBJECTIVES: To identify age differences in physical activity (PA) participation
      for women. METHODS: Data from 3,952 women 25+ from the 2003-2006 National Health
      and Nutrition Examination Surveys (NHANES) were used to analyze participation
      patterns for 17 PA types. RESULTS: The top five leisure PAs by participation rate
      for all ages were walking (42%), dancing (20%), treadmill (15%), biking (11%),
      and yoga (10%). Participation in running, dancing, treadmill, and team sports
      declined around ages 35 to 44, and participation in household PA, walking,
      weightlifting, and hiking declined around ages 55 to 64. At age 75+ further
      substantial decline in most activities occurred. Nativity status was the most
      important moderator for age-related PA decline. CONCLUSIONS: Total PA declines
      with age but significant decline does not occur until ages 55 to 64. Major
      decline in leisure PA participation starts earlier at ages 35 to 44. While age
      related declining patterns differ for different activities, the top five most
      popular leisure activities are similar for all age groups.

PMID- 23867629
TI  - Staff knowledge and perceptions of sexuality and dementia of older adults in
      nursing homes.
AB  - OBJECTIVES: Adults hold negative attitudes toward sexual expression in late life.
      We investigated knowledge and attitudes about older adult sexuality and dementia
      among staff in nursing homes (NHs). METHOD: We acquired staff demographics,
      knowledge of dementia and sexuality, and attitudes of sexuality. Staff
      participated in focus groups and received continuing education credit. RESULTS:
      The three NHs had an average census of 178 beds. Participants' (N=100) mean age
      was 38.53. The most common type of sexual contact reported was nondemented male
      with nondemented female (67.5%), followed by demented male with demented female
      (53.6%). Participants endorsed neutral attitudes about late-life sexuality. Focus
      groups revealed a need for more training and effective interventions to balance
      resident safety and autonomy. DISCUSSION: Staffs' knowledge of sexuality and
      dementia, desire for guidance in "managing" sexual expression, and neutral
      attitudes toward late-life sexuality supports the need for educational
      interventions on sexuality and dementia in NH.

PMID- 23867630
TI  - Mental and physical health consequences of spousal health shocks among older
      adults.
AB  - OBJECTIVE: To examine how the experience of a negative health event (i.e., onset
      of heart disease, diabetes, lung disease, cancer, or stroke) of one spouse
      affects the mental and physical well-being of the other partner as measured by
      depressive symptoms and self-reported health. METHODS: We employ latent growth
      curve analysis and examine adults 50+ using six waves of data (1998-2008) from
      the Health and Retirement Study. RESULTS: One spouse's health shock affects the
      health of the other partner. Results indicate that a spouse's onset of a severe
      health condition worsens the mental health of women and the self-reported health
      of men. DISCUSSION: These findings illustrate that the family context of spouses
      is important to consider when examining health.

PMID- 23867631
TI  - Induction of pulmonary hypertensive changes by extracellular vesicles from
      monocrotaline-treated mice.
AB  - AIMS: Circulating endothelium-derived extracellular vesicles (EV) levels are
      altered in pulmonary arterial hypertension (PAH) but whether they are biomarkers
      of cellular injury or participants in disease pathogenesis is unknown.
      Previously, we found that lung-derived EVs (LEVs) induce bone marrow-derived
      progenitor cells to express lung-specific mRNA and protein. In this study, we
      sought to determine whether LEV or plasma-derived EV (PEV) alter pulmonary
      vascular endothelial or marrow progenitor cell phenotype to induce pulmonary
      vascular remodelling. METHODS AND RESULTS: LEV, PEV isolated from monocrotaline
      (MCT-EV)- or vehicle-treated mice (vehicle-EV) were injected into healthy mice.
      Right ventricular (RV) hypertrophy and pulmonary vascular remodelling were
      assessed by RV-to-body weight (RV/BW) and blood vessel wall thickness-to-diameter
      (WT/D) ratios. RV/BW, WT/D ratios were elevated in MCT- vs. vehicle-injected mice
      (1.99 +/- 0.09 vs. 1.04 +/- 0.09 mg/g; 0.159 +/- 0.002 vs. 0.062 +/- 0.009%).
      RV/BW, WT/D ratios were higher in mice injected with MCT-EV vs. mice injected
      with vehicle-EV (1.63 +/- 0.09 vs. 1.08 +/- 0.09 mg/g; 0.113 +/- 0.02 vs. 0.056
      +/- 0.01%). Lineage-depleted bone marrow cells incubated with MCT-EV and marrow
      cells isolated from mice infused with MCT-EV had greater expression of
      endothelial progenitor cell mRNAs and mRNAs abnormally expressed in PAH than
      cells incubated with vehicle-EV or isolated from vehicle-EV infused mice. MCT-EV
      induced an apoptosis-resistant phenotype in murine pulmonary endothelial cells
      and lineage-depleted bone marrow cells incubated with MCT-EV induced pulmonary
      hypertension when injected into healthy mice. CONCLUSIONS: EV from MCT-injured
      mice contribute to the development of MCT-induced pulmonary hypertension. This
      effect may be mediated directly by EV on the pulmonary vasculature or by
      differentiation of bone marrow cells to endothelial progenitor cells that induce
      pulmonary vascular remodelling.

PMID- 23867632
TI  - The constituents and mechanisms of generation of 'endothelial cell--colony
      forming units'.
AB  - AIMS: The formation of endothelial cell-colony forming units (EC-CFUs) is
      increased by vascular injury, although their function in vivo is unclear. We,
      therefore, examined the constituents of EC-CFUs and the mechanisms of their
      generation. METHODS AND RESULTS: We performed immunohistochemical
      characterization of EC-CFUs and their mononuclear precursors. Using fluorescent
      activated cell sorting, we evaluated the capacity of mononuclear subpopulations
      to generate EC-CFUs, and monitored their migratory behaviour when co-incubated
      with EC-CFUs. Time-lapse microscopy was used to observe colony maturation.
      Cellular proliferation within EC-CFUs was assessed using bromodeoxyuridine (BrdU)
      and anti-proliferative agents. EC-CFUs exhibited typical endothelial
      characteristics; however, several endothelial markers were weakly expressed or
      absent. Macrophage and lymphocyte antigens were intensely expressed. EC-CFUs
      readily incorporated BrdU, and failed to develop in the presence of anti
      proliferative agents (P < 0.01; n = 12). Time-lapse microscopy demonstrated that
      the characteristic EC-CFU 'spindle cells' are not EC-CFU progeny, but are
      mononuclear cells migrating towards, and incorporating into colonies. Only
      CD14(+) monocytes were necessary for EC-CFU formation. CD14 expression was
      progressively down-regulated during colony maturation (P < 0.001; n = 6).
      Although unable to generate EC-CFUs directly, CD34(+) cells could differentiate
      into CD14(+) cells and potentiate EC-CFU formation. CONCLUSIONS: EC-CFUs exhibit
      endothelial characteristics, but are predominantly CD14(+) derived macrophages
      and are a potent stimulus for lymphocyte migration. Proliferation is necessary
      for EC-CFU generation; however, colony growth also occurs as a result of
      leucocyte migration. Although confirmatory in vivo studies are required, EC-CFU
      formation likely reflects leucocyte activation as a reparatory response to
      vascular denudation or tissue ischaemia.

PMID- 23867633
TI  - HSPA12B and repairing the heart: beauty in simplicity.

PMID- 23867634
TI  - Successful everolimus treatment in a patient with advanced pancreatic
      neuroendocrine tumor who developed everolimus-induced interstitial lung disease
      on two occasions: a case report.
AB  - Chemotherapy-associated interstitial lung disease (ILD) is often fatal, and the
      chemotherapeutic regimen generally cannot be resumed. ILD associated with the
      mammalian target of rapamycin (mTOR) inhibitor everolimus has many features
      distinct from chemotherapy-associated ILD. We present the case of a 58-year-old
      woman with an advanced pancreatic neuroendocrine tumor with liver metastases, in
      whom everolimus treatment was maintained and resulted in a partial response
      despite two occurrences of everolimus-induced ILD during a 31-month treatment
      period until disease progression. Physicians treating with everolimus should
      monitor patients closely for ILD and should apply appropriate management
      strategies to optimize the possibility of maintaining everolimus therapy.

PMID- 23867635
TI  - Long-term social isolation in the adulthood results in CA1 shrinkage and
      cognitive impairment.
AB  - Social isolation in adulthood is a psychosocial stressor that can result in
      endocrinological and behavioral alterations in different species. In rodents,
      controversial results have been obtained in fear conditioning after social
      isolation at adulthood, while neural substrates underlying these differences are
      largely unknown. Neural cell adhesion molecule (NCAM) and its polysialylated form
      (PSA-NCAM) are prominent modulators of synaptic plasticity underlying memory
      processes in many tasks, including fear conditioning. In this study, we used
      adult female Octodon degus to investigate the effects of long-term social
      isolation on contextual and cued fear conditioning, and the possible modulation
      of the synaptic levels of NCAM and PSA-NCAM in the hippocampus. After 61/2 months
      of social isolation, adult female degus showed a normal auditory-cued fear
      memory, but a deficit in contextual fear memory, a hippocampal dependent task.
      Subsequently, we observed reduced hippocampal synaptic levels of PSA-NCAM in
      isolated compared to grouped-housed female degus. No significant differences were
      found between experimental groups in hippocampal levels of the three main
      isoforms of NCAM (NCAM180, NCAM140 and NCAM120). Interestingly, social isolation
      reduced the volume of the hippocampal CA1 subfield, without affecting the volume
      of the CA3 subregion or the total hippocampus. Moreover, attenuated body weight
      gain and reduced number of granulocytes were detected in isolated animals. Our
      findings indicate for the first time, that long-term social isolation of adult
      female animals induces a specific shrinkage of CA1 and a decrease in synaptic
      levels of PSA-NCAM in the hippocampus. These effects may be related to the
      deficit in contextual fear memory observed in isolated female degus.

PMID- 23867636
TI  - Motor memory in childhood: early expression of consolidation phase gains.
AB  - Are children faster than adults in consolidating procedural knowledge? In adults,
      the expression of the full benefits of motor practice requires a few hours of
      consolidation and sleep. Here we show that, although the processes generating the
      delayed gains continued beyond the first few hours post-training, children
      expressed significant gains as early as 1 h post-training, in the awake state. 

PMID- 23867637
TI  - [Diagnosis and follow-up with 18F-fluorodeoxiglucose positron emission
      tomography/computed tomography of extraosseous myeloma].

PMID- 23867638
TI  - Extensive hypermetabolic pattern of brown adipose tissue activation on 18F-FDG
      PET/CT in a patient diagnosed of catecholamine-secreting para-vesical
      paraganglioma.
AB  - The widespread use of (18)F-FDG PET-CT scanning in oncological patients has
      allowed to demonstrate the existence of metabolically active brown fat, also
      called brown adipose tissue (BAT), in adult humans, and specifying its anatomical
      distribution in vivo. As physiological determinants to BAT (18)F-FDG uptake has
      been identified gender, age, temperature, and body mass index. We have observed
      extensive activation of the BAT, including the mesenteric region, in a patient
      with a catecholamine-secreting para-vesical paranganglioma. The extensive BAT
      activation could be secondary to adrenergic stimulation due to excess of
      circulating norepinephrine concentration. 

PMID- 23867639
TI  - Spectroscopic investigations of the charge-transfer interaction between the drug
      reserpine and different acceptors: towards understanding of drug-receptor
      mechanism.
AB  - The study of the charge-transfer interaction of the drugs may be useful in
      understanding the drug-receptor interactions and the mechanism of drug action.
      Structural and thermal stability of charge-transfer (CT) complexes formed between
      the drug reserpine (Res) as a donor and quinol (QL), picric acid (PA),
      tetracyanoquinodimethane (TCNQ) or dichlorodicyanobenzoquinone (DDQ) as acceptors
      were reported. Elemental analysis, electronic absorption, spectrophotometric
      titration, IR, Raman, (1)H NMR and X-ray powder diffraction (XRD) were used to
      characterize the new products. The thermal stability of the synthesized CT
      complexes was investigated using thermogravimetric (TG) analyses, and the
      morphology and particle size of these complexes were obtained from scanning
      electron microscopy (SEM). The stoichiometry of the complexes (donor:acceptor
      molar ratio) was determined to be 1:1 for all complexes. Accordingly the formed
      CT complexes could be formulated as [(Res)(QL)], [(Res)(PA)], [(Res)(TCNQ)] and
      [(Res)(DDQ)]. It was found that the obtained CT complexes are nanoscale, semi
      crystalline particles, thermally stable and formed through spontaneous reaction.
      The results obtained herein are satisfactory for estimation of drug Res in the
      pharmaceutical form. 

PMID- 23867640
TI  - Thermal analysis and vibrational spectroscopic characterization of the boro
      silicate mineral datolite - CaBSiO4(OH).
AB  - The objective of this work is to determine the thermal stability and vibrational
      spectra of datolite CaBSiO4(OH) and relate these properties to the structure of
      the mineral. The thermal analysis of datolite shows a mass loss of 5.83% over a
      700-775 degrees C temperature range. This mass loss corresponds to 1 water (H2O)
      molecules pfu. A quantitative chemical analysis using electron probe was
      undertaken. The Raman spectrum of datolite is characterized by bands at 917 and
      1077cm(-1) assigned to the symmetric stretching modes of BO and SiO tetrahedra. A
      very intense Raman band is observed at 3498cm(-1) assigned to the stretching
      vibration of the OH units in the structure of datolite. BOH out-of-plane
      vibrations are characterized by the infrared band at 782cm(-1). The vibrational
      spectra are based upon the structure of datolite based on sheets of four- and
      eight-membered rings of alternating SiO4 and BO3(OH) tetrahedra with the sheets
      bonded together by calcium atoms. 

PMID- 23867641
TI  - Computational and spectral studies of 1,6-diphenyl-1,3,5-hexatriene (DPH)
      multicomponent solutions.
AB  - The multicomponent 1,6-diphenyl-1,3,5-hexatriene+tetrahydrofuran+water+ethanol
      (DPH+THF+W+E) solutions with variable content in water were studied by
      computational and spectral means. The computational results that indicate micelle
      formation in multicomponent solutions at high water content were correlated by
      the independence of the wavenumber in the maximum of the fluorescence on the
      solvent composition. 

PMID- 23867642
TI  - Synthesis, characterization and SERS activity of biosynthesized silver
      nanoparticles.
AB  - Silver nanoparticles were rapidly synthesized using Moringa oleifera flower
      extract as the reducing agent shows surface plasmon resonance peak at 439nm. The
      size and shape of the nanoparticles controlled by varying the concentration of M.
      oleifera flower extract in the reaction medium. The synthesized silver
      nanoparticles were well-dispersed spherical nanoparticles with the average size
      of 14nm. The retinoic acid present in M. oleifera flower extract used as reducing
      agent and proteins was responsible for capping of the bioreduced silver
      nanoparticles. The obtained nanoparticle shows size-dependent SERS activity. The
      SERS spectrum indicates that the pyridine adsorbed on the silver surface in a
      stand-on orientation via its nitrogen lone pair electrons. 

PMID- 23867643
TI  - Label-free gold nanoparticles for the determination of neomycin.
AB  - A new spectrophotometric method for the determination of neomycin has been
      developed. The method is based on aggregation of label-free gold nanoparticles
      leading to change in absorption spectra and color of the solution. Influence of
      different factors (the concentration of ethylenediaminetetraacetate (EDTA), pH,
      the concentrations of neomycin and the nanoparticles) on the aggregation and
      analytical performance of the method was investigated. EDTA plays an important
      role not only as a masking agent to eliminate interferences of metal cations but
      strongly affects the sensitivity of the nanoparticles relative to neomycin. The
      method allows to determine neomycin with detection limit of 28ngmL(-1). It was
      applied to analysis of eye- and ear-drops. The sample pretreatment is simply done
      by diluting the formulation with water. 

PMID- 23867644
TI  - Synthesis, crystal structure and spectral properties of 2-[(1-Methyl-2
      benzimidazolyl)azo]-p-cresol: an experimental and theoretical study.
AB  - 2-[(1-Methyl-2-benzimidazolyl)azo]-p-cresol (HL), containing phenolic-OH function
      and benzimidazole moiety has been synthesized and characterized. The chemical,
      electronic structure and photophysical properties have been studied by
      spectroscopic analysis abetted with DFT and TDDFT calculations. The change in
      electronic spectra of HL by titration with aq. NaOH is studied and well supported
      by TDDFT calculations. The structure is confirmed by single crystal X-ray study.
      In the unit cell, two HL molecules are H-bonded with H2O molecule and forms
      dimmeric structure. The molecule forms 2D-supramolecular structure by inter
      molecular H-bonding and pi-pi interactions. 

PMID- 23867645
TI  - Computational studies of the electronic, conductivities, and spectroscopic
      properties of hydrolysed Ru(II) anticancer complexes.
AB  - The mechanism of activation of metal-based anticancer agents was reported to be
      through hydrolysis. In this study, computational method was used to gain insight
      to the correlation between the chemistry of the hydrolysis and the anticancer
      activities of selected Ru(II)-based complexes. Interestingly, we observed that
      the mechanism of activation by hydrolysis and their consequential anticancer
      activities is associated with favourable thermodynamic changes, higher
      hyperpolarizability (beta), lower band-gap and higher first-order net current.
      The Fermi contact (FC) and spin dipole (SD) are found to be the two most
      significant Ramsey terms that determine the spin-spin couplings (J(HZ)) of most
      of the existing bonds in the complexes. Many of the computed properties give
      insights into the change in the chemistry of the complexes due to hydrolysis.
      Besides strong correlations of the computed properties to the anticancer
      activities of the complexes, using the quantum theory of atoms in a molecule
      (QTAIM) to analyse the spectroscopic properties shows a stronger correlation
      between the spectroscopic properties of Ru atom to the reported anticancer
      activities than the sum over of the spectroscopic properties of all atoms in the
      complexes. 

PMID- 23867646
TI  - Vibrational spectral studies and non-linear optical properties of L-leucine L
      leucinium picrate: a Density Functional Theory approach.
AB  - Single crystals of l-leucine l-leucinium picrate were grown by slow evaporation
      at room temperature and were characterized by X-ray powder diffraction study to
      confirm the crystalline nature of the synthesized compound. The optimized
      molecular structure, vibrational spectra and the optical properties were
      calculated by the Density Functional Theory (DFT) method using the B3LYP function
      with the 6-31G(d) basis set. Good consistency is found between the calculated
      results and the experimental structure, IR, and Raman spectra. The detailed
      interpretation of the vibrational modes was carried out. The natural bond orbital
      (NBO) analysis, confirms the occurrence of intermolecular hydrogen bonds that are
      responsible for the stabilization of the title compound, leading to high
      nonlinear optical (NLO) activity. The lowering in the HOMO and LUMO energy gap
      explains the eventual charge transfer interactions that take place within the
      molecules. 

PMID- 23867647
TI  - Synthesis of a novel water-soluble zinc phthalocyanine and its CT DNA-damaging
      studies.
AB  - A novel 3-(4-methoxybenzylamino) propanoic acid substituted water-soluble zinc
      phthalocyanine (CNPcZn) was synthesized. The interaction between CNPcZn with calf
      thymus DNA (CT DNA) was studied using spectroscopic methods. The studies
      indicated that CNPcZn has strong affinity to CT DNA, and furthermore, CNZnPc
      showed excellent photodamaging activity to CT DNA. Above results indicated that
      such CNPcZn has great potential to be used as an effective photosensitizer in the
      field of photodynamic therapy. 

PMID- 23867648
TI  - The demand for an educational smartphone app.

PMID- 23867650
TI  - Pea lectin inhibits growth of Ehrlich ascites carcinoma cells by inducing
      apoptosis and G2/M cell cycle arrest in vivo in mice.
AB  - Pea (Pisum sativum L.) lectin is known to have interesting pharmacological
      activities and of great interest on biomedical research. In the current research
      pea lectin was purified followed by ion exchange chromatography on DEAE column
      and affinity chromatography on glucose-sepharose column. The lectin shown 11.7
      84% inhibitory effect against Ehrlich ascites carcinoma (EAC) cells at the
      concentration range of 8-120 MUg/ml in RPMI 1640 medium as determined by MTT
      assay. Pea lectin was also shown 63% and 44% growth inhibition against EAC cells
      in vivo in mice when administered 2.8 mg/kg/day and 1.4 mg/kg/day (i.p.)
      respectively for five consequent days. When Pea lectin injected into the EAC
      bearing mice for 10 days its significantly increased the hemoglobin and RBC with
      the decreased of WBC levels toward the normal. Apoptotic cell morphological
      change of the treated EAC cells of mice was determined by fluorescence and
      optical microscope. Interestingly, cell growth inhibition of the lectin was
      significantly reduced in the presence of caspase inhibitors. Treatment with the
      lectin caused the cell cycle arrest at G2/M phase of EAC cells which was
      determined by flow cytometry. The expression of apoptosis-related genes, Bcl-2,
      Bcl-X and Bax was evaluated by reverse transcriptase polymerase chain reaction
      (RT-PCR). Intensive increase of Bax gene expression and totally despaired of Bcl
      2 and Bcl-X gene expression were observed in the cells treated with Pea lectin
      for five consecutive days.

PMID- 23867649
TI  - Lignans from Carthamus tinctorius suppress tryptophan breakdown via indoleamine
      2,3-dioxygenase.
AB  - Seed extracts of Carthamus tinctorius L. (Asteraceae), safflower, have been
      traditionally used to treat coronary disease, thrombotic disorders, and menstrual
      problems but also against cancer and depression. A possible effect of C.
      tinctorius compounds on tryptophan-degrading activity of enzyme indoleamine 2,3
      dioxygenase (IDO) could explain many of its activities. To test for an effect of
      C. tinctorius extracts and isolated compounds on cytokine-induced IDO activity in
      immunocompetent cells in vitro methanol and ethylacetate seed extracts were
      prepared from cold pressed seed cakes of C. tinctorius and three lignan
      derivatives, trachelogenin, arctigenin and matairesinol were isolated. The
      influence on tryptophan breakdown was investigated in peripheral blood
      mononuclear cells (PBMCs). Effects were compared to neopterin production in the
      same cellular assay. Both seed extracts suppressed tryptophan breakdown in
      stimulated PBMC. The three structurally closely related isolates exerted
      differing suppressive activity on PBMC: arctigenin (IC50 26.5MUM) and
      trachelogenin (IC50 of 57.4MUM) showed higher activity than matairesinol (IC50
      >200MUM) to inhibit tryptophan breakdown. Effects on neopterin production were
      similar albeit generally less strong. Data show an immunosuppressive property of
      compounds which slows down IDO activity. The in vitro results support the view
      that some of the anti-inflammatory, anticancer and antidepressant properties of
      C. tinctorius lignans might relate to their suppressive influence on tryptophan
      breakdown. 

PMID- 23867651
TI  - Berberine's effect on periodontal tissue degradation by matrix
      metalloproteinases: an in vitro and in vivo experiment.
AB  - Periodontal disease involves tissue destruction caused by interactions among
      bacterial antigens and inflammatory mediators including matrix metalloproteinases
      (MMPs). Berberine, an isoquinoline alkaloid isolated from medicinal herbs, can
      inhibit the degradative action of extracellular MMPs. The effect of berberine on
      the periodontal expression of MMPs was examined in vitro and in vivo.
      Gelatinolytic activity of pro-MMP-2, MMP-2, and MMP-9 in the human gingival
      fibroblast and/or U-937 was compared after treatment with Porphyromonas
      gingivalis lipopolysaccharide (P.g. LPS) in four medias containing 0, 1, 10 and
      100MUM of berberine each. Twelve animals were divided into three groups for the
      study: (A) non-ligation, (B) ligation, and (C) ligation-plus-berberine (75mg/kg
      berberine by gastric lavage daily); and the effect of berberine on periodontal
      destruction was evaluated in the ligature-induced periodontitis in rats for 8
      days by micro computerized tomography (micro-CT), histology and
      immunohistochemistry (IHC). An enhancing effect of P.g. LPS on MMP activities was
      identified, with a greater effect on fibroblasts/U937 co-culture than on either
      culture alone. When berberine was added to the LPS-treated cultures, the
      activities of MMPs were significantly reduced in dose-dependent manner. In the
      animals, the trends of the following parameters were compared. 1. Micro-CT
      distances between cemento-enamel junction (CEJ) and dental alveolar bone crest:
      B>C>A. 2. Histometrically measured crest bone levels: B>C>A. 3. Amount of
      collagen deposited in tissue areas: A>C>B. 4. Attachment loss: B>C~A. 5.
      Connective tissue (CT) attachment: B>either A or C. 6. Expression of cells
      stained positive for MMP-2 and -9 by IHC: B>C>A. In conclusion, berberine
      demonstrated in vitro an inhibitory effect on P.g. LPS-enhanced MMP activities of
      HGF and U937 macrophages, reducing in vivo gingival tissue degradation in
      periodontitic rats. We thus propose that berberine may slow periodontal
      degradation through the regulation of MMPs in periodontitis induced by bacterial
      plaque. 

PMID- 23867652
TI  - Separation and identification of 1,2,4-trihydroxynaphthalene-1-O-glucoside in
      Impatiens glandulifera Royle.
AB  - Methanolic extract from lyophilized roots of Impatiens glandulifera Royle was
      analyzed by high performance liquid chromatography using DAD and FLD detection
      and this revealed one dominant highly fluorescent very unstable substance. The
      stability of this derivative is strongly dependent on the plant material drying
      procedure and extraction procedure used. The structure of the substance was
      established as 1,2,4-trihydroxynaphthalene-1-O-glucoside (THNG) according LC-MS
      and NMR measurements. When lyophilized plant material was extracted with methanol
      an almost four times higher amount of THNG was found in the extract, compared to
      the amount of 2-hydroxy-1,4-naphthoquinone obtained, while in the case of the
      same lyophilized plant material extracted with water there was no THNG in the
      extract. The main compounds in this case was 2-hydroxy-1,4-naphthoquinone. In the
      plant material dried at the laboratory temperature and extracted by methanol
      there are only traces of THNG. 

PMID- 23867653
TI  - Dendrimers in layer-by-layer assemblies: synthesis and applications.
AB  - We review the synthesis of dendrimer-containing layer-by-layer (LbL) assemblies
      and their applications, including biosensing, controlled drug release, and bio
      imaging. Dendrimers can be built into LbL films and microcapsules by alternating
      deposition of dendrimers and counter polymers on the surface of flat substrates
      and colloidal microparticles through electrostatic bonding, hydrogen bonding,
      covalent bonding, and biological affinity. Dendrimer-containing LbL assemblies
      have been used to construct biosensors, in which electron transfer mediators and
      metal nanoparticles are often coupled with dendrimers. Enzymes have been
      successfully immobilized on the surface of electrochemical and optical
      transducers by forming enzyme/dendrimer LbL multilayers. In this way, high
      performance enzyme sensors are fabricated. In addition, dendrimer LbL films and
      microcapsules are useful for constructing drug delivery systems because
      dendrimers bind drugs to form inclusion complexes or the dendrimer surface is
      covalently modified with drugs. Magnetic resonance imaging of cancer cells by
      iron oxide nanoparticles coated with dendrimer LbL film is also discussed. 

PMID- 23867655
TI  - Recent advances in psychoneuroimmunology relevant to schizophrenia therapeutics.
AB  - PURPOSE OF REVIEW: Immunological understanding of neurological and cognitive
      alterations of schizophrenia has made a significant breakthrough in unfolding the
      pathophysiological mechanisms of schizophrenia, at least in a group of patients.
      Such psychoneuroimmunological aberrations essentially argue for an alternative
      treatment approach based on immunomodulation in schizophrenia. RECENT FINDINGS:
      Recent findings in schizophrenia have shown exaggerated immuno-inflammatory
      responses due to persistent systemic inflammation and neuroinflammation involving
      microglia activation. The existing antipsychotic drugs have shown substantial
      benefits in the control of positive symptoms, but they have not demonstrated
      adequate immuno-dampening effects specifically and effectively. However, a group
      of emerging nonsteroidal as well as other anti-inflammatory drugs currently being
      used as an adjunct therapy seem to exhibit increased target specificity and
      effectiveness in reducing symptom severity to some extent. SUMMARY: The anti
      inflammatory drugs that have been shown to reduce the levels of pro-inflammatory
      mediators and inhibit microglia activation have paved the way for better outcomes
      of schizophrenia treatment. However, many of the currently tested anti
      inflammatory drugs often lack methodological robustness. The identification of
      novel target(s) that will integrate the processes evoked by various risk
      determinants into a common signalling pathway is urgently required, and this may
      take immunomodulation into a new therapeutic domain in schizophrenia.

PMID- 23867654
TI  - Reactive oxygen species regulate context-dependent inhibition of NFAT5 target
      genes.
AB  - The activation of nuclear factor of activated T cells 5 (NFAT5), a well-known
      osmoprotective factor, can be induced by isotonic stimuli, such as activated Toll
      like receptors (TLRs). It is unclear, however, how NFAT5 discriminates between
      isotonic and hypertonic stimuli. In this study we identified a novel context
      dependent suppression of NFAT5 target gene expression in RAW 264.7 macrophages
      stimulated with lipopolysaccharide (LPS) or a high salt (NaCl) concentration.
      Although LPS and NaCl both used NFAT5 as a core transcription factor, these
      stimuli mutually inhibited distinct sets of NFAT5 targets within the cells.
      Although reactive oxygen species (ROS) are essential for this inhibition, the
      source of ROS differed depending on the context: mitochondria for high salt and
      xanthine oxidase for TLRs. Specifically, the high salt-induced suppression of
      interleukin-6 (IL-6) production was mediated through the ROS-induced inhibition
      of NFAT5 binding to the IL-6 promoter. The context-dependent inhibition of NFAT5
      target gene expression was also confirmed in mouse spleen and kidney tissues that
      were cotreated with LPS and high salt. Taken together, our data suggest that ROS
      function as molecular sensors to discriminate between TLR ligation and osmotic
      stimuli in RAW 264.7 macrophages, directing NFAT5 activity toward proinflammatory
      or hypertonic responses in a context-dependent manner. 

PMID- 23867656
TI  - Biomarkers of stress in behavioural medicine.
AB  - PURPOSE OF REVIEW: In recent years, a growing interest has emerged in behavioural
      medicine to examine the role of acute and chronic stress as a predisposing and
      contributing factor to physical health and illness. For a deeper understanding of
      these associations, research is in need of biological markers for alterations in
      biological stress systems. This review will summarize a selection of important
      recent findings in this area of research. RECENT FINDINGS: We will focus on
      essential peripheral stress-sensitive physiological systems, that is, the
      hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the immune
      system. We will present findings on commonly used stress biomarkers (cortisol,
      alpha-amylase, pro-inflammatory cytokines) regarding alterations in basal
      activity and stress-dependent reactivity in these systems, and discuss selected
      findings on intervention-induced changes of these biomarkers. SUMMARY: This
      review will highlight new developments and guide readers in their choice of
      suitable study designs and outcomes in behavioural medicine. The reviewed studies
      included here encourage optimism that the employment of stress biomarkers in
      behavioural medicine has the potential to significantly improve our understanding
      of physical health and illness.

PMID- 23867657
TI  - Ways to improve the patient-physician relationship.
AB  - PURPOSE OF REVIEW: This article revises the main conclusions from recent reviews
      and research, about the different dimensions that shape the patient-physician
      relationship, delineating specific areas of intervention that would reinforce the
      quality of this interaction. RECENT FINDINGS: The selected articles reflect the
      permanent interest that exists about this topic. Within the most promissory
      findings significant associations were found from statistical as well as clinical
      standpoints. These associated verbal and non-verbal communication skills, as well
      as the empathizing ability of the physician, with clinical results of the
      patients, were measured with subjective parameters (e.g. patient satisfaction)
      and especially objective ones (e.g. physiological markers). Nevertheless, the
      results are still not robust and cannot be translatable. SUMMARY: The
      implications of these studies are at a conceptual and instrumental level. A
      better precision of the dimensions and variables that define the patient
      physician relationship will permit the design of educational strategies and
      training that will empower the physician for an interaction with his patients of
      greater technical and relational efficiency.

PMID- 23867658
TI  - The psychology of chronic obstructive pulmonary disease.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a leading
      cause of morbidity and mortality worldwide and is associated with significant
      individual and socioeconomic burden. Recent research has begun to acknowledge the
      important role of psychological factors in the course and management of the
      disease. Therefore, the present review provides an overview on recent findings on
      psychological factors in COPD with a specific focus on anxiety and depression.
      RECENT FINDINGS: Recent findings demonstrate high levels of anxiety and
      depression in COPD patients which are related to a considerably worse course of
      the disease. The exact causes for these findings are widely unknown, but several
      potential mechanisms have been suggested. Moreover, anxiety and depression often
      remain undetected and untreated in COPD patients. Although some beneficial
      effects of respective psychotropic and psychotherapeutic treatments have been
      reported, future well-controlled studies regarding their efficacy are mandatory.
      SUMMARY: Comorbid anxiety and depression in patients with COPD are a major health
      problem requiring intensified research activities. Future studies need to examine
      the exact links between COPD and these psychological comorbidities, and how their
      detection and treatment can be improved in the clinical setting.

PMID- 23867659
TI  - Functional somatic symptoms in childhood and adolescence.
AB  - PURPOSE OF REVIEW: Functional somatic symptoms (FSS) are common in children and
      adolescents, but explanatory models that synthesize research findings are
      lacking. This article reviews the studies published from January 2012 to March
      2013 that investigate the neurophysiological mechanisms that may underlie FSS.
      RECENT FINDINGS: Studies from diverse medical disciplines suggest that FSS are
      associated with functional differences in hypothalamic-pituitary-adrenal
      function, imbalances in vagal-sympathetic tone, upregulation of immune
      inflammatory function, and primed cognitive-emotional responses that serve to
      amplify reactivity to threatening stimuli, thereby contributing to the subjective
      experience of somatic symptoms. SUMMARY: FSS appear to reflect dysregulations of
      the stress system. When seemingly disparate research findings are interpreted
      together within an overarching 'stress-system' framework, a coherent explanatory
      model begins to emerge.

PMID- 23867660
TI  - The impact of social cognition training on recovery from psychosis.
AB  - PURPOSE OF REVIEW: Social cognition training is an emerging intervention, which
      aims to ameliorate impairment in social interaction and improve functional
      outcomes in persons with a psychosis. This article reviews the research conducted
      on the impact of this intervention published in English language journals over
      the past 2 years. RECENT FINDINGS: Social cognition training comprises three
      types of programs; targeted, broad-based, and comprehensive - targeted programs
      being the most effective. Programs largely focus on the domains of facial affect,
      or emotion recognition (FAR), Theory of Mind (ToM), and attributional bias. There
      is some evidence that ToM is amenable to change, but not FAR and attributional
      bias. SUMMARY: Interventions designed to ameliorate impairment in social
      functioning largely involve a skills training laboratory model underpinned by
      social learning theory. The evidence for the effectiveness of current social
      cognition training strategies to improve functional outcome for persons with
      psychosis in general and schizophrenia in particular remains equivocal. Clearly,
      further work is required beyond the laboratory training model and future research
      may well benefit from the inclusion of longitudinal naturalistic studies.

PMID- 23867661
TI  - Close relationships in psychiatric disorders.
AB  - PURPOSE OF REVIEW: The current article provides an in-depth analysis of the
      social variable in the biopsychosocial model (BPS) of psychiatric disorders.
      Based on existing evidence, we posit understanding the role of the romantic
      partner is instrumental in the etiology of psychiatric disorders. RECENT
      FINDINGS: The link between psychiatric disorders and relationship well being is
      bidirectional; depression can lead to decreased relationship satisfaction, and
      relationship quality can lead to the development of affective disorders
      (depression and anxiety). Expanding upon traditional individual-oriented
      therapeutic approaches, examining psychiatric disorders from a we-disease
      perspective (couple's therapy) proves to be beneficial in treating and preventing
      relapse. SUMMARY: As the notion of we-disease suggests, each couple may benefit
      from a joint approach whereby each partner is viewed as an integral contributing
      factor to the process of recovery.

PMID- 23867662
TI  - Classification systems in psychiatry: diagnosis and global mental health in the
      era of DSM-5 and ICD-11.
AB  - PURPOSE OF REVIEW: The development of the fifth edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-5) and- of the 11th edition of the
      International Classification of Disease (ICD-11) have led to renewed attention to
      the conceptual controversies surrounding the nosology of mental disorder. This
      article reviews recent work in this area, and suggests potential ways forward for
      psychiatric nosology, focusing in particular on the need for improved
      classification approaches for public and global mental health. RECENT FINDINGS:
      DSM-5 and ICD-11 have taken somewhat different approaches, but both appropriately
      emphasize the importance of clinical utility and diagnosic validity in
      psychiatric nosology. The Research Domain Criteria framework provides a useful
      focus on the individual-level causal mechanisms that are relevant to
      vulnerability to mental disorder. An analogous approach to societal-level causal
      mechanisms would be useful from a public and global mental health perspective.
      SUMMARY: In their day-to-day work, clinicians will continue to use the fuzzy
      constructs operationally defined and narratively depicted in DSM-5 and ICD-11.
      Advances in our understanding of the individual-level and society-level causal
      mechanisms that contribute to vulnerability to mental disorder may ultimately
      lead to improved classification systems, and in turn to better individualized
      care as well as improved global mental health.

PMID- 23867663
TI  - Mid-term outcomes in HIV-positive patients after primary total hip or knee
      arthroplasty.
AB  - We hypothesized that infection rates following total joint arthroplasty (TJA) in
      those with the human immunodeficiency virus (HIV) without hemophilia or drug use
      would be similar to rates in HIV-negative patients. Records at an urban HIV
      referral hospital were searched for patients who underwent primary total hip and
      knee arthroplasty from 2003 to 2010. The primary outcome was revision for
      infection. 372 HIV-negative and 22 HIV-positive TJA patients met inclusion
      criteria. The HIV-positive group had more deep infections than the HIV-negative
      group (9.1% v 2.2%, P=0.102). There were no infections in those with AIDS
      defining CD4 counts. Those with HIV may have a higher risk of developing a deep
      infection. A low CD4 count is not an absolute contraindication to TJA in HIV
      positive patients. 

PMID- 23867664
TI  - India needs an implementable antibiotic policy.

PMID- 23867665
TI  - Rapid diagnosis of infectious diseases: the role of giant African pouched rats,
      dogs and honeybees.
AB  - Early detection of infection in an individual is an important strategy to prevent
      transmission and spread of the infection - in the community or among patients
      admitted in a health care facility. Over the past decade, there have been rapid
      advances in technology in an attempt to provide rapid, accurate tests for
      diagnosis of infectious diseases. With this in perspective, the use of animals'
      superior olfactory sensitivity to sniff out infectious diseases holds promise. 

PMID- 23867666
TI  - Rapid identification of clinical mycobacterial isolates by protein profiling
      using matrix assisted laser desorption ionization-time of flight mass
      spectrometry.
AB  - PURPOSE: The purpose of this study was to evaluate the identification of
      Mycobacterium tuberculosis which is often plagued with ambiguity. It is a time
      consuming process requiring 4-8 weeks after culture positivity, thereby delaying
      therapeutic intervention. For a successful treatment and disease management,
      timely diagnosis is imperative. We evaluated a rapid, proteomic based technique
      for identification of clinical mycobacterial isolates by protein profiling using
      matrix assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS). MATERIALS AND METHODS: Freshly grown mycobacterial isolates were
      used. Acetonitrile/trifluoroacetic acid extraction procedure was carried out,
      following which cinnamic acid charged plates were subjected to identification by
      MALDI-TOF MS. RESULTS: A comparative analysis of 42 clinical mycobacterial
      isolates using the MALDI-TOF MS and conventional techniques was carried out.
      Among these, 97.61% were found to corroborate with the standard methods at genus
      level and 85.36% were accurate till the species level. One out of 42 was not in
      accord with the conventional assays because MALDI-TOF MS established it as
      Mycobacterium tuberculosis (log (score)>2.0) and conventional methods established
      it to be non-tuberculous Mycobacterium. CONCLUSIONS: MALDI-TOF MS was found to be
      an accurate, rapid, cost effective and robust system for identification of
      mycobacterial species. This innovative approach holds promise for early
      therapeutic intervention leading to better patient care.

PMID- 23867667
TI  - Over-expression of gene encoding heat shock protein 70 from Mycobacterium
      tuberculosis and its evaluation as vaccine adjuvant.
AB  - BACKGROUND: Heat shock proteins (Hsps) are evolutionary ancient and highly
      conserved molecular chaperons found in prokaryotes as well as eukaryotes. Hsp70
      is a predominant member of Hsp family. Microbial Hsp70s (mHsp70s) have acquired
      special significance in immunity since they have been shown to be potent
      activators of the innate immune system and generate specific immune responses
      against tumours and infectious agents. OBJECTIVES: The present study was aimed to
      clone express and purify recombinant Hsp70 from the Mycobacterium tuberculosis
      and characterise it immunologically. The study also aimed at determining the
      potential of recombinant M. tuberculosis heat shock protein (rMTB-Hsp70) as
      adjuvant or antigen carrier. MATERIALS AND METHODS: Cloning of M. tuberculosis
      heat shock protein (MTB-Hsp70) amplicon was carried out using the pGEMT-Easy
      vector although for expression, pProExHTb prokaryotic expression vector was used.
      Purification of recombinant Hsp70 was carried out by nickel-nitrilotriacetic acid
      (Ni-NTA) affinity chromatography. For immunological characterization and
      determining the adjuvant effect of MTB-Hsp70, BALB/c mice were used. The data
      obtained was statistically analysed. RESULTS: Hsp70 gene was cloned, sequenced
      and the sequence data were submitted to National Center for Biotechnology
      Information (NCBI). Recombinant MTB-Hsp70 was successfully over-expressed using
      the prokaryotic expression system and purified to homogeneity. The protein was
      found to be immunodominant. Significant adjuvant effect was produced by the rMTB
      Hsp70 when inoculated with recombinant outer membrane protein 31; however, effect
      was less than the conventionally used the Freund's adjuvant. CONCLUSION: Protocol
      standardised can be followed for bulk production of rHsp70 in a cost-effective
      manner. Significant adjuvant effect was produced by rMTB-Hsp70; however, the
      effect was than Freund's adjuvant. Further, studies need to be carried out to
      explore its applicability as carrier of antigen.

PMID- 23867668
TI  - A rapid and low-cost microscopic observation drug susceptibility assay for
      detecting TB and MDR-TB among individuals infected by HIV in South India.
AB  - BACKGROUND: The converging epidemics of HIV and tuberculosis (TB) pose one of the
      greatest public health challenges of our time. Rapid diagnosis of TB is essential
      in view of its infectious nature, high burden of cases, and emergence of drug
      resistance. OBJECTIVE: The purpose of this present study was to evaluate the
      feasibility of implementing the microscopic observation drug susceptibility
      (MODS) assay, a novel assay for the diagnosis of TB and multi-drug-resistant
      tuberculosis (MDR-TB) directly from sputum specimens, in the Indian setting.
      MATERIALS AND METHODS: This study involved a cross-sectional, blinded assessment
      of the MODS assay on 1036 suspected cases of pulmonary TB in HIV-positive and HIV
      negative patients against the radiometric method, BD-BACTEC TB 460 system.
      RESULTS: Overall, the sensitivity, specificity, positive predictive value, and
      negative predictive value of the MODS assay in detecting MTB among TB suspected
      patients were 89.1%, 99.1%, 94.2%, 95.8%, respectively. In addition, in the
      diagnosis of drug-resistant TB, the MODS assay was 84.2% sensitive for those
      specimens reporting MDR, 87% sensitivity for those specimens reporting INH mono
      resistance, and 100% sensitive for specimens reporting RIF mono-resistance. The
      median time to detection of TB in the MODS assay versus BACTEC was 9 versus 21
      days (P<0.001). CONCLUSION: Costing 5 to 10 times lesser than the automated
      culture methods, the MODS assay has the potential clinical utility as a simple
      and rapid method. It could be effectively used as an alternative method for
      diagnosing TB and detection of MDR-TB in a timely and affordable way in resource
      limited settings.

PMID- 23867669
TI  - Distribution of human papillomavirus genotypes in women with cervical alterations
      from north Argentina.
AB  - BACKGROUND: Cervical cancer remains a major public health problem in northern
      Argentina, showing the highest mortality rate in the country (approximately 22
      cases/100000 women). OBJECTIVE: The aim of this study was to provide
      epidemiological data on the prevalence and type distribution of human
      papillomavirus (HPV) in women with pre-neoplastic lesions before the massive
      introduction of HPV vaccination in the country. MATERIALS AND METHODS: Exfoliated
      cervical cells were collected to screen for HPV using the widely known MY09/11
      PCR, followed by the restriction fragment-length polymorphism (RFLP) technique
      from a total of 714 women with previously diagnosed atypical squamous cells of
      undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LG
      SIL) and high-grade squamous intraepithelial lesion (HG-SIL). RESULTS: Overall
      HPV prevalence was 48.2% in ASCUS (24 different HPV types detected), 66.5% in LG
      SIL (37 HPV types detected) and 82.6% in HG-SIL (16 HPV types detected). HPV-16
      was the most prevalent type among all cases. With respect to multiple HPV
      infections, 9.6% were observed in ASCUS, 14.3% in LG-SIL and 11.4% in HG-SIL.
      CONCLUSION: The major strength of our study is the assessment of a large series
      of women with cytological alterations in this region. The information attained
      will be useful as a regional baseline for future epidemiological vigilance, in
      the context of the national HPV vaccination program.

PMID- 23867670
TI  - Detection of the common resistance genes in Gram-negative bacteria using gene
      chip technology.
AB  - OBJECTIVE: To design a resistance gene detection chip that could, in parallel,
      detect common clinical drug resistance genes of Gram-negative bacteria. MATERIALS
      AND METHODS: Seventy clinically significant Gram-negative bacilli (Klebsiella
      pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa,
      Acinetobacter baumannii) were collected. According to the known resistance gene
      sequences, we designed and synthesized primers and probes, which were used to
      prepare resistance gene detection chips, and finally we hybridized and scanned
      the gene detection chips. RESULTS: The results between the gene chip and
      polymerase chain reaction (PCR) were compared. The rate was consistently 100% in
      the eight kinds of resistance genes tested (TEM, SHV, CTX-M, DHA, CIT, VIM, KPC,
      OXA-23). One strain of Pseudomonas aeruginosa had the IMP, but it was not found
      by gene chip. CONCLUSION: The design of Gram-negative bacteria-resistant gene
      detection chip had better application value.

PMID- 23867671
TI  - Intraperitoneal inoculation of Haemophilus influenzae local isolates in BALB/c
      mice model in the presence and absence of virulence enhancement agents.
AB  - PURPOSE: Haemophilus influenzae (Hi), predominantly type b accounts for
      approximately 4% of cases of community-acquired and nosocomial meningitis, in
      adults. The objective of this study was to evaluate the pathogenicity of local Hi
      isolates (type b, f and non-typable) in BALB/c mice in the presence of virulence
      enhancement agents. MATERIALS AND METHODS: Three different concentrations of the
      Hi isolates were inoculated intraperitoneally in BALB/c mice in the presence of
      2% hemoglobin and 4% mucin as virulence enhancing agents (VEA). The ability of
      the isolates to produce bacteremia, the percent survival and lethal dose (LD50)
      were recorded in different challenge groups. RESULTS: The 3 Haemophilus
      influenzae type b (Hib) isolates used in study were able to show virulence in
      BALB/c mice model only in the presence of VEA and their LD50 decreased
      significantly when 2% hemoglobin and 4% mucin were used. All survived animals
      showed bacteremia within 4 h of inoculation which was cleared within 18 h.
      Significant differences (P<0.01) in the virulence and survival percentage of Hib
      challenge groups were observed based on their dose of inoculation and VEA. None
      of the isolates were able to induce infection in the absence of VEA. Non-type b
      isolates failed to produce disease in the mice models even at the highest
      inoculated dose (108 cfu) and in the presence of VEA. CONCLUSIONS: BALB/c mice
      appeared suitable for evaluating the virulence of Hib strains, and 2% hemoglobin
      with 4% mucin an appropriate concentration for inducing infection in this animal
      model.

PMID- 23867672
TI  - Comparison of different methods of detection of enteric pathogenic protozoa.
AB  - PURPOSE: The study was conducted to compare different methods of detection of
      pathogenic protozoan parasites in stool specimens of People Living with HIV/AIDS
      (PLHA). MATERIALS AND METHODS: Stool specimens of 242 HIV sero-positive patients
      were examined using the wet mount technique, modified Ziehl-Neelsen's (ZN)
      staining, auto-fluorescence and auramine fluorescence staining. Patient
      specimens, 94 and 40 out of 242, were also subjected to Giardia antigen detection
      using an enzyme immunoassay and Cryptosporidium antigen detection by immuno
      chromatography, respectively. For calculation of sensitivity, specificity,
      positive and negative predictive values, light microscopy of wet mounts and
      modified ZN stained smears for Giardia and Coccidia, respectively, were
      considered as gold standards. RESULTS: Sensitivity of auto-fluorescence, auramine
      O staining and antigen detection techniques was found to be 100% as compared to
      the routine standards. The specificity of auto-fluorescence was 90.6% and 100%
      for Cyclospora and Isospora, respectively; that of auramine-O staining was 98.9%
      for Cryptosporidium, 99.30% for Cyclospora and 100% for Isospora; and that of
      antigen detection was 90.6% and 97.7% for Cryptosporidium and Giardia,
      respectively. CONCLUSION: In laboratories requiring screening of large number of
      stool specimens for detection of protozoan parasites, fluorescence microscopy and
      antigen detection can be useful techniques. Confirmation of positive results,
      however, needs to be done with the standard techniques.

PMID- 23867673
TI  - Prevalence of intestinal parasitic infections in HIV-infected individuals and
      their relationship with immune status.
AB  - BACKGROUND AND OBJECTIVES: Intestinal parasitic infection is a common entity in
      patients infected with human immunodeficiency virus (HIV). These infections may
      lead to fatal complications in the immuno suppressed individuals. The aim of the
      present study was to determine the prevalence of intestinal parasitic infections
      in HIV sero-positive patients and their relationship with the immune status of
      individuals. MATERIALS AND METHODS: Fecal samples from 100 HIV sero-positive and
      an equal number of HIV sero-negative individuals were collected and examined for
      enteric parasites by direct microscopy. CD4 counts were carried out in only HIV
      sero-positive patients. Prevalence of intestinal parasites in patients with CD4
      count<200 cells/MUl, 200-499 cells/MUl, and >=500 cells/MUl in HIV-infected
      patients were compared. RESULTS: Enteric parasites were detected in 59.3% HIV
      infected patients with CD4 count<200 cells/MUl as compared with 23.5% in patients
      with CD4 count>200 cells/MUl (P<0.01). Prevalence of coccidian parasites was
      significantly (P<0.01) higher (14%) in HIV sero-positive subjects compared with
      HIV sero-negative subjects (2%). Isospora belli (25%) was the most common
      parasite with CD4 count<200 cells/MUl, followed by Cryptosporidium parvum
      (12.5%). Prevalence of intestinal parasitic infections was significantly higher
      in patients with diarrhea, 73.6% than without diarrhea, 25.9%, (P<0.05). The mean
      CD4 count of HIV sero-positive patients presenting with diarrhea was
      significantly (P<0.01) lower (181.26+/-135.14) than without diarrhea (352.02+/
      204.03). CONCLUSION: This study emphasizes the need for routine screening of
      parasites especially in patients with lower CD4 count so as to decrease the
      morbidity by ensuring the early treatment of the cases.

PMID- 23867674
TI  - Polymorphisms in major cytokine genes: a study among human immunodeficiency Virus
      1 serodiscordant couples in Mumbai, India.
AB  - PURPOSE: Polymorphism in cytokine genes may affect its production, which play an
      important role in modulation of human immunodeficiency virus (HIV) infection.
      Evaluation of these polymorphisms might help to understand why some individuals
      remain uninfected in spite of several exposures to HIV infection, such as the
      negative spouses of discordant couples. The aim of this study was to evaluate the
      association of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes and
      their receptors with HIV infection in serodiscordant couples, attending the
      Integrated Counselling and Testing Centre of a Municipality Hospital. MATERIALS
      AND METHODS: At the end of at least 2 years of follow up, 42 couples were
      confirmed as being serodiscordant. Genotyping was carried out in blood samples of
      these couples using the polymerase chain reaction-sequence-specific amplification
      method. RESULTS: Significantly high frequency of interleukin-1 receptor
      antagonist IL-1RA mspa 11100 CC (P=0.04), tumor necrosis factor-alpha TNF-alpha 
      238 AG (P=0.01) and IL-4 -33 TT (P=0.01) was observed in HIV seropositives (HSP)
      while frequency of TNF-alpha -238 GG (P=0.02) was significantly high among the
      exposed uninfected (EU). However, application of Bonferroni correction identified
      only two SNPs i.e., TNF-alpha -238 AG and IL-4 -33 TT to be significantly
      associated with the acquisition of HIV. In remaining cytokine genes, no
      significant association was observed. CONCLUSION: Our study highlighted possible
      association of certain specific polymorphisms with HIV transmission, whereas
      presence or absence of certain other polymorphism in EU individuals might be
      offering protection from HIV infection. These variations at the genetic level
      might help to explore new insights into treatment and HIV prevention strategies.

PMID- 23867675
TI  - Anaerobic culture on growth efficient bi-layered culture plate in a modified
      candle jar using a rapid and slow combustion system.
AB  - Success for maximum isolation of anaerobes depends on maintaining critically low
      oxygen levels throughout and growth in a reduced medium with exclusion of
      inhibitory substances. Hence a dual system was used equipped with candle
      combustion for instant exhaustion of major part of oxygen from a sealed jar,
      along with acidified steel wool for residual oxygen purging. For inhibitory
      substances removal, test anaerobes were grown on anaerobic medium layered on
      buffer charcoal agar bed. After 48 hours incubation average colony sizes were
      compared with that of growths in conventional Gas-Pak system. Better growths were
      noted in the innovative system. 

PMID- 23867676
TI  - Anti-ganglioside antibodies in patients with Guillain Barre syndrome and other
      neurological disorders.
AB  - A study was performed on 59 Guillain-Barre syndrome (GBS) cases, 58 neurological
      controls (NC) and 60 non-neurological controls (NNC) to investigate the
      association of anti-ganglioside antibodies in GBS and other neurological
      disorders. Campylobacter jejuni was isolated from 5.7% of GBS patients. Anti
      ganglioside immunoglobulin G was present in 82% and immunoglobulin M in 46% in
      acute inflammatory demyelinating polyneuropathy patients, 70% and 44%
      respectively in acute motor axonal neuropathy subgroup and 38% each in acute
      motor sensory axonal neuropathy subgroup. Though high intensity of anti
      gangliosides was present in the GBS patients, the NC patients also had adequate
      anti-gangliosides compared with the NNC group. 

PMID- 23867677
TI  - Plasmodium vivax induced myocarditis: a rare case report.
AB  - Malaria is one of the commonest parasitic disease in the tropics since ages.
      However the plasmodium still continues to give surprises to all of us. In the
      similar context we report a case of Plasmodium vivax induced myocarditis in a 20
      year old male and review the literature related to this rare entitiy. 

PMID- 23867678
TI  - Subcutaneous mucor zygomycosis with potential life-threatening visceral
      complication.
AB  - A mass in right supraclavicular fossa in a diabetic patient mimicking
      tuberculosis (TB) adenitis that ultimately proved to be subcutaneous zygomycosis.
      A high degree of clinical suspicion is needed for diagnosis especially when these
      lesions occur at typical sites for the more common indolent infections like TB.
      This case is being presented not only because of its rarity, but to emphasize the
      role of early diagnosis and appropriate treatment to prevent serious
      complications due to proximity to major structures. Fluconazole was used despite
      not being the ideal drug, solely due to cost constraints. Our patient responded
      well. However, we do emphasize that response to fluconazole is the exception
      rather than the rule. 

PMID- 23867679
TI  - Severe diarrhoea due to Cystoisospora belli in renal transplant patient on
      immunosuppressive drugs.
AB  - Cystoisospora belli, formerly known as Isospora belli, protozoal parasite endemic
      to many regions of the world including the Caribbean, Central and South America,
      Africa, and South-East Asia. It is frequently encountered in patients with
      acquired immunodeficiency syndrome (AIDS) and is considered to be an AIDS
      defining illness. Chronic severe watery diarrhoea due to C. belli has also been
      reported in other immunodeficiency states. C. belli infection in immunosuppressed
      patients has rarely been described. We describe severe diarrhoea due to C. belli
      in a human immunodeficiency virus-negative renal transplant recipient on
      immunosuppressive drugs. Oocysts of C. belli were detected in direct smear
      preparation of the diarrheic stool sample of the patient. The patient responded
      to combination treatment with Bactrim-double-strength (trimethoprim
      sulfamethoxazole) and Nitazoxanide.

PMID- 23867680
TI  - Neonatal listeriosis followed by nosocomial infection.
AB  - Neonatal listeriosis is widely reported, but this is the first case reported in
      Serbia. A newborn developed respiratory distress syndrome 2 hours after delivery
      and was admitted to the neonatal intensive care unit. Initial empirical therapy
      was inappropriate. Consequently, on the second day, the patient developed
      meningitis. Listeria monocytogenes was isolated from the tracheal aspirate,
      blood, periumbilical swab, and cerebrospinal fluid. After bacteriology results,
      the therapy was changed to ampicillin and meropenem. On day 11 of
      hospitalization, the patient developed nosocomial infection due to multidrug
      resistant Stenotrophomonas maltophilia. Since therapeutic options were limited,
      the patient was treated with ciprofloxacin. After 26 days of hospitalization the
      patient showed complete recovery and was discharged with no apparent sequelae.
      This case showed the importance of bacteriological examination in cases of
      infections caused by uncommon organisms. Pediatricians should be aware of the
      neonatal infection caused by Stenotrophomonas maltophilia. 

PMID- 23867681
TI  - Co-infections with Ureaplasma parvum, Mycoplasma hominis and Chlamydia
      trachomatis in a human immunodeficiency virus positive woman with vaginal
      discharge.
AB  - A 30-year-old human immunodeficiency virus (HIV)-1 infected woman presented with
      vaginal discharge and associated vulval irritation. The vaginal swabs tested
      positive for Ureaplasma parvum and Mycoplasma hominis by both culture and
      polymerase chain reaction (PCR). The specimen also tested positive for Chlamydia
      trachomatis deoxyribonucleic acid (DNA) by cryptic plasmid and omp1 gene PCR
      assays. The patient was successfully treated with azithromycin based on the
      antibiotic susceptibility testing results of U. parvum and M. hominis by
      microbroth dilution. Since sexually transmitted infections enhance the
      transmission of HIV, HIV-positive patients should be screened routinely for these
      pathogens. 

PMID- 23867682
TI  - A case of dual infection in a paediatric trauma victim of primary cutaneous
      aspergillosis caused by Aspergillus flavus and Aspergillus terreus.
AB  - Aspergillus spp. are widely distributed throughout the environment. They are
      opportunistic pathogens causing infection at various sites in the body such as
      lungs, sinuses, eyes, skin, central nervous system etc., Primary cutaneous
      aspergillosis is an uncommon disease entity. Primary infections usually occur at
      sites having disruption of the skin and usually occur in burn patients, trauma
      and surgical patients. A 4-year-old girl who was run over by a truck and suffered
      extensive de-gloving injury to bilateral lower limbs developed greenish discharge
      and scaly lesions around the wound margins after 50 days of hospital stay. The
      skin biopsy demonstrated the presence of thin septate hyphae branching at acute
      angles and culture demonstrated growth of Aspergillus flavus and Aspergillus
      terreus. The child was started on voriconazole therapy for 3 weeks and the lesion
      healed satisfactorily. Subsequent skin biopsy culture was negative for fungi.
      Prompt diagnosis and management of such cases can salvage the limbs in severe
      trauma cases. 

PMID- 23867683
TI  - A case report of an uncommon phaeoid fungal infection in nasal polyposis and
      review of literature.
AB  - Nasal polyposis is an inflammatory condition of mucous membrane of the nose and
      paranasal sinuses with unknown aetiology. Massive nasal polyps can obstruct the
      nasal cavity causing discomfort and lowered quality of life. Thus, aetiological
      diagnosis is important for treatment, especially in recurrent nasal polyposis. We
      present a rare case of pansinusitis with bilateral ethmoidal polyps caused by an
      unusual phaeoid fungus Fonsecaea pedrosoi in a 65-year-old immunocompetent male
      from a rural background. The diagnosis was made by endoscopic nasal examination;
      high resolution computed tomography of the paranasal sinuses, detection of fungal
      hyphae in 10% potassium hydroxide wet mount and culture. 

PMID- 23867684
TI  - Polymerase chain reaction for the diagnosis of extra-pulmonary tuberculosis: need
      of the hour.

PMID- 23867685
TI  - Carbapenemase producing Proteus: any therapeutic suggestions?

PMID- 23867686
TI  - How to liven-up an overhead projector presentation!

PMID- 23867687
TI  - A novel pathogen for gastroenteritis: Laribacter hongkongensis.

PMID- 23867688
TI  - Cystisospora belli infection in a non-human immunodeficiency virus
      immunosuppressed patient.

PMID- 23867689
TI  - First report of the emergence of New Delhi metallo-beta-lactamase-1 producing
      Acinetobacter junii in Nanjing, China.

PMID- 23867690
TI  - Importance of performing routine quality control testing of antimicrobial discs.

PMID- 23867691
TI  - Siderophore production among clinical and healthy skin isolates of Acinetobacter
      species.

PMID- 23867692
TI  - Efficacy of disinfectants on clinical isolates of Acinetobacter species.

PMID- 23867693
TI  - Mucocutaneous leishmaniasis: mucosal manifestations in an endemic country.

PMID- 23867694
TI  - Beyond masculinity: testosterone, gender/sex, and human social behavior in a
      comparative context.
AB  - Largely based on pre-theory that ties high testosterone (T) to masculinity, and
      low T to femininity, high T is mainly studied in relation to aggression, mating,
      sexuality, and challenge, and low T with parenting. Evidence, however, fails to
      support this, and the social variability in T is better accounted for by a
      competition-nurturance trade-off as per the Steroid/Peptide Theory of Social
      Bonds (van Anders et al., 2011). Four key domains are discussed: adult-infant
      interactions, sexual desire, sexual behavior, and partnering. Empirical
      engagements with gender/sex are shown to lead to important insights over
      assumptions about masculinity-femininity. Humans are discussed within a
      comparative framework that attends to cross-species principles informed by human
      insights alongside human-specific particularities like social constructions,
      which are critical to evolutionary understandings of the social role of T. This
      paper thus integrates seemingly orthogonal perspectives to allow for
      transformative approaches to an empirically-supported social phenomenology of T. 

PMID- 23867695
TI  - Feasibility of using low density polyethylene sheets to detect atmospheric
      organochlorine pesticides in Alexandria, Egypt.
AB  - Egypt is a major agricultural country in Africa with a known past of
      organochlorine pesticides (OCPs) application, yet data on atmospheric levels of
      OCPs in Egypt is sparse. Low density polyethylene (LDPE) passive samplers were
      therefore deployed for 3 weeks each at 11 locations in July, 2010 and January,
      2011 in Alexandria to screen for gas-phase OCPs. Performance reference compounds
      were used to investigate the uptake kinetics. Field-derived sampler-air
      partitioning coefficients (KPE-As) for OCPs were significantly correlated against
      the compounds' subcooled liquid vapor pressure (log PL): [log KPE-A = -0.77 +/-
      0.07 log PL + 6.35 +/- 0.13 (R(2) = 0.90; n = 17; SE = 0.19; p < 0.001)].
      Estimated and measured OCP concentrations in Alexandria agreed well (factor
      difference <= 2) indicating the feasibility of monitoring OCPs using LDPEs. OCP
      concentrations ranged from <LOD to 168 pg/m(3). Calculated isomeric ratios
      indicated recent usage of chlordanes and endosulfans.

PMID- 23867696
TI  - Passive air sampling of organochlorine pesticides and polychlorinated biphenyls
      in the Yangtze River Delta, China: concentrations, distributions, and cancer risk
      assessment.
AB  - The Yangtze River Delta (YRD) has been quickly industrialized and urbanized.
      Passive air sampling of organochlorine pesticides (OCPs) and polychlorinated
      biphenyls (PCBs) was carried out in the YRD in 2010-2011 to investigate their
      spatiotemporal distributions and estimate the risk of cancer from their
      inhalation. Annual concentrations were 151, 168, 18.8, 110, 17.9, and 35.0 pg m(
      3) for HCB, ?DDTs, ?HCHs, ?chlordane, mirex, and PCBs, respectively. The highest
      OCP and PCB concentrations were generally detected in the autumn and winter. The
      average concentrations of OCPs and PCBs for the different site groups followed
      the order urban ~ urban-rural transition > rural. The lifetime excess cancer
      risks from the inhalation of OCPs and PCBs were <1.0 * 10(-6). The predicted
      cancer cases per lifetime associated with the inhalation of OCPs and PCBs are 12,
      7, and 4 per ten thousand people for urban, urban-rural transition, and rural
      areas, respectively.

PMID- 23867697
TI  - Soil humic-like organic compounds in prescribed fire emissions using nuclear
      magnetic resonance spectroscopy.
AB  - Here we present the chemical characterization of the water-soluble organic carbon
      fraction of atmospheric aerosol collected during a prescribed fire burn in
      relation to soil organic matter and biomass combustion. Using nuclear magnetic
      resonance spectroscopy, we observed that humic-like substances in fire emissions
      have been associated with soil organic matter rather than biomass. Using a
      chemical mass balance model, we estimated that soil organic matter may contribute
      up to 41% of organic hydrogen and up to 27% of water-soluble organic carbon in
      fire emissions. Dust particles, when mixed with fresh combustion emissions,
      substantially enhances the atmospheric oxidative capacity, particle formation and
      microphysical properties of clouds influencing the climatic responses of
      atmospheric aeroso. Owing to the large emissions of combustion aerosol during
      fires, the release of dust particles from soil surfaces that are subjected to
      intense heating and shear stress has, so far, been lacking. 

PMID- 23867698
TI  - An intercomparison of satellite-derived ground-level NO2 concentrations with
      GMSMB modeling results and in-situ measurements--a North American study.
AB  - This paper investigates the biases associated with the ground-level nitrogen
      dioxide (NO2) concentrations derived from the satellite Ozone Monitoring
      Instrument (OMI) NO2 data through comparisons with the modeling and the
      monitoring results for the state of California in 2008. The seasonal and annual
      average ground-level NO2 concentrations are both analyzed from the OMI using the
      local NO2 profile obtained from the GEOS-Chem simulation. The OMI-derived ground
      level NO2 concentrations are then compared with the NO2 concentrations predicted
      by a GIS-Based Multi-Source and Multi-Box model (GMSMB) and the in-situ
      measurements, correlation coefficients among the three sets of results are all
      above 0.84 with an average slope of 0.81 +/- 0.04. Particularly, various biases
      associated with the three data sets have been analyzed, and the OMI-derived NO2
      concentrations and the GMSMB modeling results have been proven to be essential
      for assessing regional air pollutant exposure risks with the aid of the extensive
      remote sensing database. 

PMID- 23867699
TI  - Role of arbuscular mycorrhizal fungus Rhizophagus custos in the dissipation of
      PAHs under root-organ culture conditions.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are one of the most common contaminants
      in soil. Arbuscular mycorrhizal (AM) fungi make host plants resistant to
      pollutants. This study aims to evaluate the impact of anthracene, phenanthrene
      and dibenzothiophene on the AM fungus Rhizophagus custos, isolated from soil
      contaminated by heavy metals and PAHs, under monoxenic conditions. We found a
      high level of tolerance in R. custos to the presence of PAHs, especially in the
      case of anthracene, in which no negative effect on AM-colonized root dry weight
      (root yield) was observed, and also a decrease in the formation of anthraquinone
      was detected. Increased PAH dissipation in the mycorrhizal root culture medium
      was observed; however, dissipation was affected by the level of concentration and
      the specific PAH, which lead us to a better understanding of the possible
      contribution of AM fungi, and in particular R. custos, to pollutant removal.

PMID- 23867700
TI  - Design and field-scale implementation of an "on site" bioremediation treatment in
      PAH-polluted soil.
AB  - An "on site" bioremediation program was designed and implemented in soil polluted
      with polycyclic aromatic hydrocarbons (PAHs), especially naphthalene. We began by
      characterizing the soil's physical and chemical properties. A microbiological
      screening corroborated the presence of microorganisms capable of metabolizing
      PAHs. We then analyzed the viability of bioremediation by developing laboratory
      microcosms and pilot scale studies, to optimize the costs and time associated
      with remediation. The treatment assays were based on different types of
      biostimulants, such as a slow or fast-release fertilizer, combined with
      commercial surfactants. Once the feasibility of the biostimulation was confirmed,
      a real-scale bioremediation program was undertaken in 900 m(3) of contaminated
      soil. The three-step design reduced PAH contamination by 94.4% at the end of
      treatment (161 days). The decrease in pollutants was concomitant with the
      selection of autochthonous bacteria capable of degrading PAHs, with Bacillus and
      Pseudomonas the most abundant genera.

PMID- 23867701
TI  - Combination of poly-gamma-glutamate and cyclophosphamide enhanced antitumor
      efficacy against tumor growth and metastasis in a murine melanoma model.
AB  - Conventional chemotherapeutic regimens often accompany severe side effects and
      fail to induce complete regression of chemoresistant or relapsing metastatic
      cancers. The need for establishing more efficacious anticancer strategies led to
      the development of a combined modality treatment of chemotherapy in conjunction
      with immunotherapy or radiotherapy. It has been reported that poly-gamma
      glutamate (gamma-PGA), a natural polymer composed of glutamic acids, increases
      antitumor activity by activating antigen-presenting cells and natural killer (NK)
      cells. Here, we investigated the antitumor effect of gamma-PGA in combination
      with cyclophosphamide in a murine melanoma model. Whereas cyclophosphamide alone
      directly triggered apoptosis of tumor cells in vitro, gamma-PGA did not show
      cytotoxicity in tumor cells. Instead, it activated macrophages, as reflected by
      the upregulation of surface activation markers and the secretion of
      proinflammatory factors, such as nitric oxide and tumor necrosis factor alpha.
      When the antitumor effects were examined in a mouse model, combined treatment
      with cyclophosphamide and gamma-PGA markedly suppressed tumor growth and
      metastasis. Notably, gamma-PGA treatment dramatically increased the NK cell
      population in lung tissues, coinciding with decreased metastasis and increased
      survival. These data collectively suggest that gamma-PGA can act as an
      immunotherapeutic agent that exhibits a synergistic antitumor effect in
      combination with conventional chemotherapy. 

PMID- 23867702
TI  - Improving the chitinolytic activity of Bacillus pumilus SG2 by random
      mutagenesis.
AB  - Bacillus pumilus SG2, a halotolerant strain, expresses two major chitinases
      designated ChiS and ChiL that were induced by chitin and secreted into the
      supernatant. The present work aimed to obtain a mutant with higher chitinolytic
      activity through mutagenesis of Bacillus pumilus SG2 using a combination of UV
      irradiation and nitrous acid treatment. Following mutagenesis and screening on
      chitin agar and subsequent formation of halos, the mutated strains were examined
      for degradation of chitin under different conditions. A mutant designated AV2-9
      was selected owing to its higher chitinase activity. To search for possible
      mutations in the whole operon including ChiS and ChiL, the entire chitinase
      operon, including the intergenic region, promoter, and two areas corresponding to
      the ChiS and ChiL ORF, was suquenced. Nucleotide sequence analysis of the
      complete chitinase operon from the SG2 and AV2-9 strains showed the presence of a
      mutation in the catalytic domain (GH18) of chitinase (ChiL). The results
      demonstrated that a single base change had occurred in the ChiL sequence in AV2-
      9. The wild-type chitinase, ChiL, and the mutant (designated ChiLm) were cloned,
      expressed, and purified in E. coli. Both enzymes showed similar profiles of
      activity at different ranges of pH, NaCl concentration, and temperature, but the
      mutant enzyme showed approximately 30% higher catalytic activity under all the
      conditions tested. The results obtained in this study showed that the thermal
      stability of chitinase increased in the mutant strain. Bioinformatics analysis
      was performed to predict changes in the stability of proteins caused by mutation.

PMID- 23867703
TI  - A WblA-binding protein, SpiA, involved in Streptomyces oxidative stress response.
AB  - The Streptomyces coelicolor wblA gene is known to play a negative role in both
      antibiotic biosynthesis and the expression of genes responding to oxidative
      stress. Recently, WhcA, a WblA ortholog protein, was confirmed to interact with
      dioxygenase-encoding SpiA (stress protein interacting with WhcA) in
      Corynebacterium glutamicum. We describe here the identification of a SpiA
      ortholog SCO2553 protein (SpiAsc) that interacts with WblA in S. coelicolor.
      Using heterologous expression in E. coli and in vitro pull-down assays, we show
      that WblA specifically binds SpiAsc, and is influenced by oxidants such as
      diamide. These data indicate that the interaction between WblA and SpiAsc is not
      only specific but also modulated by the redox status of the cell. Moreover, a
      spiAsc-disruption mutant exhibited a less sensitive response to the oxidative
      stress induced by diamide present in solid plate culture. Real-time RT-PCR
      analysis also showed that transcription levels of oxidative stress response genes
      (sodF, sodF2, and trxB) were higher in the spiAsc-deletion mutant than in wild
      type S. coelicolor. These results show that SpiAsc negatively regulates WblA
      during oxidative stress responses in S. coelicolor. 

PMID- 23867704
TI  - In-depth characterization of wastewater bacterial community in response to algal
      growth using pyrosequencing.
AB  - Microalgae have been regarded as a natural resource for sustainable materials and
      fuels, as well as for removal of nutrients and micropollutants from wastewater,
      and their interaction with bacteria in wastewater is a critical factor to
      consider because of the microbial diversity and complexity in a variety of
      wastewater conditions. Despite their importance, very little is known about the
      ecological interactions between algae and bacteria in a wastewater environment.
      In this study, we characterized the wastewater bacterial community in response to
      the growth of a Selenastrum gracile UTEX 325 population in a real municipal
      wastewater environment. The Roche 454 GS-FLX Titanium pyrosequencing technique
      was used for indepth analysis of amplicons of 16S rRNA genes from different
      conditions in each reactor, with and without the algal population. The algal
      growth reduced the bacterial diversity and affected the bacterial community
      structure in the wastewater. The following in-depth analysis of the deep
      sequenced amplicons showed that the algal growth selectively stimulated
      Sphingobacteria class members, especially the Sediminibacterium genus population,
      in the municipal wastewater environment. 

PMID- 23867705
TI  - Aluminum inhibits the growth of hydroxyapatite crystals developed on a biomimetic
      methacrylic polymer.
AB  - PROJECT: Aluminum (Al) is an increasing problem in biomedicine since it can
      interact with phosphates. Bone is one of the preferential target tissues of Al
      deposition: Al interacts with mineralization and/or bone cell activities. We
      searched the influence of Al deposition in hydroxyapatite developed on a
      biomimetic polymer (carboxymethylated poly(2-hydroxyethyl-methacrylate)) which
      mimics bone mineralization in the absence of cells. PROCEDURES: Pellets of
      polymer were incubated for 5 days in a synthetic body fluid (SBF) to induce
      mineralization, then 21 days in SBF containing 20, 40 and 60 MUg/L Al(3+). Other
      pellets were incubated in SBF containing commercial Al foil (33 mg/vial) either
      in 1, 2 or 6 pieces. The mineral deposits were dissolved in HCl and Ca(2+),
      PO(4)(3-) and Al(3+) content was measured. Hydroxyapatite was characterized by
      SEM and X energy-dispersive X-ray analysis (EDX). RESULTS: The amount of Al(3+)
      was dose-dependently increased in Ca/P deposits on the polymer pellets. At high
      concentration (or with the 6 Al foils) growth of hydroxyapatite calcospherite was
      inhibited; only calcified plates emerging from the polymer were observed. Pellets
      incubated with 1 and 2 Al foils exhibited a reduction in calcospherite diameter
      and an increase in the Al(3+)/Ca(2+) ratio. EDX identified Al in the mineral
      deposits. CONCLUSIONS: In this acellular model, Al(3+) altered the growth of
      calcospherites at low concentration and inhibited their development at high
      concentration. In SBF, a release of Al(3+) from aluminum foils also inhibited
      mineralization. This study emphasizes the importance of Al in bone pathology and
      stresses the question of its release from biomaterials.

PMID- 23867706
TI  - Robust detection of P. aeruginosa and S. aureus acute lung infections by
      secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting:
      from initial infection to clearance.
AB  - Before breath-based diagnostics for lung infections can be implemented in the
      clinic, it is necessary to understand how the breath volatiles change during the
      course of infection, and ideally, to identify a core set of breath markers that
      can be used to diagnose the pathogen at any point during the infection. In the
      study presented here, we use secondary electrospray ionization-mass spectrometry
      (SESI-MS) to characterize the breathprint of Pseudomonas aeruginosa and
      Staphylococcus aureus lung infections in a murine model over a period of 120 h,
      with a total of 86 mice in the study. Using partial least squares-discriminant
      analysis (PLS-DA) to evaluate the time-course data, we were able to show that
      SESI-MS breathprinting can be used to robustly classify acute P. aeruginosa and
      S. aureus mouse lung infections at any time during the 120 h infection/clearance
      process. The variable importance plot from PLS indicates that multiple peaks from
      the SESI-MS breathprints are required for discriminating the bacterial
      infections. Therefore, by utilizing the entire breathprint rather than single
      biomarkers, infectious agents can be diagnosed by SESI-MS independent of when
      during the infection breath is tested. 

PMID- 23867707
TI  - Macronutrient content of donor human breast milk.
AB  - BACKGROUND: Nutritional analysis of donated human milk has been suggested as a
      means of optimising its use. METHODS: We analysed pooled, single donor milk
      samples using the MIRIS Human Milk Analyser to obtain values for fat, protein,
      lactose and calculated energy content. These values were compared with those of
      formula milks and then extrapolated to demonstrate whether donated human
      expressed breast milk (DEBM)+/-fortification would meet preterm nutritional
      requirements. We demonstrated the potential variability in macronutrient intake
      from unselected DEBM use by comparing energy intake from milk samples with energy
      values on the 3rd percentile (nutrient poor) with intake from milk with values on
      the 97th percentile (nutrient rich). RESULTS: 179 sequential samples from 42
      unique donors were analysed. Mean nutritional values, excluding protein, were
      comparable with those of term formula; energy 66+/-12 kcal/100 mLs, fat 4.0+/-1.4
      g/100 mLs, protein 0.9+/-0.4 g/100 mLs and lactose 6.6+/-0.7 g/100 mLs. At
      volumes of 180 mL/kg/day 119 samples (66%) would have provided minimum preterm
      energy requirements without fortification however protein levels were low and
      even with fortification 39% of samples would fail to meet the recommended preterm
      requirements. The potential difference in energy intake between nutrient-poor and
      nutrient-rich milk was 88 kcal/kg/day. INTERPRETATION: In summary our data
      confirm the nutritional variability of DEBM and demonstrate the potential of
      nutritional analysis to target the use of donor milk according to energy content.

PMID- 23867708
TI  - Parents' views on factors that help or hinder breast milk supply in neonatal care
      units: systematic review.
AB  - OBJECTIVE: To synthesise what is known about the parents' views on factors that
      help or hinder breast milk supply during their infants' hospitalisation in
      neonatal intensive care units (NICU). METHODS: A systematic search of PubMed, ISI
      WoK, PsycINFO and SciELO, targeting studies presenting original empirical data
      that examined parents' perspectives regarding breast milk supply experiences in
      NICU, was performed. Based on content analysis, three independent researchers
      synthesised the findings of seven studies. Categories of facilitators and
      barriers were identified using quotations stated in the studies: parents' breast
      milk supply experience; parents-professionals relationships; characteristics of
      the NICU; and parents' social background and expectations. RESULTS: The studies,
      five qualitative and two mixed methods, were published between 1994 and 2011.
      With heterogeneous study designs, fathers' perspectives were analysed in one
      article. Only one study defined breastfeeding. According to parents'
      perspectives, successful breast milk supply in NICU depends on coherent and
      accurate knowledge about its techniques and benefits, reinforcement of mothers'
      motivation and alignment between NICU's routines and parents' needs. Parents
      perceived issues related to their own current breast milk supply experience,
      simultaneously, as main facilitators and barriers. Parents-professionals
      relationship constituted the second group of facilitators, but the fourth of
      barriers. The characteristics of the NICU were more relevant as a barrier than as
      a facilitator. CONCLUSIONS: Although parents' perspectives are grounded on
      individual child-focused experiences, their emphasis on learning and motivation
      guided by short-term goals opens room to the collective intervention of experts.
      This may facilitate the engagement of mothers, fathers and health professionals
      on family-centred care.

PMID- 23867710
TI  - Genome-scale analysis of DNA methylation in colorectal cancer using Infinium
      HumanMethylation450 BeadChips.
AB  - Illumina's Infinium HumanMethylation450 BeadChip arrays were used to examine
      genome-wide DNA methylation profiles in 22 sample pairs from colorectal cancer
      (CRC) and adjacent tissues and 19 colon tissue samples from cancer-free donors.
      We show that the methylation profiles of tumors and healthy tissue samples can be
      clearly distinguished from one another and that the main source of methylation
      variability is associated with disease status. We used different statistical
      approaches to evaluate the methylation data. In general, at the CpG-site level,
      we found that common CRC-specific methylation patterns consist of at least 15,667
      CpG sites that were significantly different from either adjacent healthy tissue
      or tissue from cancer-free subjects. Of these sites, 10,342 were hypermethylated
      in CRC, and 5,325 were hypomethylated. Hypermethylated sites were common in the
      maximum number of sample pairs and were mostly located in CpG islands, where they
      were significantly enriched for differentially methylated regions known to be
      cancer-specific. In contrast, hypomethylated sites were mostly located in CpG
      shores and were generally sample-specific. Despite the considerable variability
      in methylation data, we selected a panel of 14 highly robust candidates showing
      methylation marks in genes SND1, ADHFE1, OPLAH, TLX2, C1orf70, ZFP64, NR5A2, and
      COL4A. This set was successfully cross-validated using methylation data from 209
      CRC samples and 38 healthy tissue samples from The Cancer Genome Atlas consortium
      (AUC = 0.981 [95% CI: 0.9677-0.9939], sensitivity = 100% and specificity = 82%).
      In summary, this study reports a large number of loci with novel differential
      methylation statuses, some of which may serve as candidate markers for diagnostic
      purposes.

PMID- 23867711
TI  - Plasmids for increased efficiency of vector construction and genetic engineering
      in filamentous fungi.
AB  - Fungal species are continuously being studied to not only understand disease in
      humans and plants but also to identify novel antibiotics and other metabolites of
      industrial importance. Genetic manipulations, such as gene deletion, gene
      complementation, and gene over-expression, are common techniques to investigate
      fungal gene functions. Although advances in transformation efficiency and
      promoter usage have improved genetic studies, some basic steps in vector
      construction are still laborious and time-consuming. Gateway cloning technology
      solves this problem by increasing the efficiency of vector construction through
      the use of lambda phage integrase proteins and att recombination sites. We
      developed a series of Gateway-compatible vectors for use in genetic studies in a
      range of fungal species. They contain nutritional and drug-resistance markers and
      can be utilized to manipulate different filamentous fungal genomes. 

PMID- 23867712
TI  - Effects of dietary isoflavones from Puerariae radix on lipid and bone metabolism
      in ovariectomized rats.
AB  - Puerariae radix, the dried root of Pueraria lobata Ohwi, is one of the earliest
      and most important edible crude herbs used for various medical purposes in
      oriental medicine. This study evaluated the metabolic effects of total
      isoflavones from P. lobata (PTIF) in ovariectomized (OVX) rats. The OVX rats were
      divided into four groups treated with distilled water, 17beta-estradiol (E2 10
      MUg/kg, once daily, i.p.) and PTIF (30 and 100 mg/kg, once daily, p.o.) for eight
      weeks. The treatments with high-dose PTIF significantly decreased the bone
      mineral density (BMD) loss in the femur and inhibited the increase in body weight
      and lipoprotein levels compared to the OVX-control group without elevating the
      serum levels of the liver enzymes, aspartate aminotransferase (AST) and alanine
      transaminase (ALT). Furthermore, PTIF exhibits a hepatoprotective effect in OVX
      induced hepatic steatosis, indicated with reduced hepatic lipid contents. Taken
      together, our findings suggest that PTIF may be useful for controlling lipid and
      bone metabolism, at least in OVX rats. Further research is necessary to determine
      whether PTIF will have the same effects in humans. 

PMID- 23867714
TI  - Characterization of the hypotensive effects of glucagon-like peptide-2 in
      anesthetized rats.
AB  - Glucagon-like peptide-2 (GLP-2) is a proglucagon-derived peptide released from
      enteroendocrine cells and neurons. We recently reported that GLP-2 induced
      hypotension. In the present study, we characterized the mechanisms of GLP-2
      induced hypotension. GLP-2 was administered peripherally or centrally to male
      Wistar rats anesthetized with urethane and alpha-chloralose. The rats were
      vagotomized or systemically pretreated with atropine, prazosin, or propranolol
      before the GLP-2 administration. The central and peripheral administration of GLP
      2 reduced mean arterial blood pressure (MAP). The maximum change of MAP (maximum
      DeltaMAP) was reduced by vagotomy or prazosin, but not propranolol. The effects
      of the central but not peripheral administration of GLP-2 were reduced by
      atropine. These results suggest that GLP-2 modulates vagal afferent inputs and
      inhibits the sympathetic nervous system in the brain to induce hypotension. 

PMID- 23867713
TI  - Role of DNA methyltransferase 1 on the altered eNOS expression in human umbilical
      endothelium from intrauterine growth restricted fetuses.
AB  - Reduced fetal growth associates with endothelial dysfunction and cardiovascular
      risk in both young and adult offspring and the nitric oxide (NO) system has been
      implicated in these effects. Epigenetic processes are likely to underlie such
      effects, but there is to date no evidence that endothelial dysfunction in early
      life results from epigenetic processes on key genes in the NO system, such as
      NOS3 (eNOS) and ARG2 (arginase-2). We determined basal DNA methylation status in
      NOS3 and ARG2 promoters, and DNA methyltransferase 1 (DNMT1) effect on eNOS and
      arginase-2 expression using human endothelial cells isolated from umbilical
      arteries (HUAEC) and veins (HUVEC) from control and intrauterine growth
      restricted (IUGR) fetuses. Compared with cells from control pregnancies, eNOS
      protein and mRNA levels were increased in HUAEC, but decreased in HUVEC, from
      IUGR, while arginase-2 levels were increased in IUGR-HUVEC. The NOS3 promoter
      showed a decrease in DNA methylation at CpG -352 in IUGR-HUAEC, and an increase
      in IUGR-HUVEC, when compared with control cells. Methylation in the hypoxia
      response element of the NOS3 promoter was increased in IUGR-HUAEC and decreased
      in HUVEC. Methylation in the AGR2 promoter in IUGR-HUVEC was decreased in a
      putative HRE, and without changes in IUGR-HUAEC. Silencing of DNMT1 expression
      normalized eNOS expression in IUGR endothelial cells, and restored the normal
      response to hypoxia in HUVEC, without effects on arginase-2. This data suggest
      that eNOS expression in IUGR-derived endothelial cells is programmed by altered
      DNA methylation, and can be reversed by transient silencing of the DNA
      methylation machinery.

PMID- 23867715
TI  - Association between physical activity and major depressive disorder among current
      or former smokers with pulmonary disease.
AB  - OBJECTIVE: To examine the association between physical activity and major
      depressive disorder (MDD) in a nationally representative sample of current or
      former smokers with pulmonary impairments. METHODS: The analyzed sample from the
      National Health and Nutrition Examination Survey (NHANES) 2007-2010 included 536
      adults who indicated that they were current or former smokers, had at least mild
      pulmonary impairment (FEV1/FVC<0.70), and provided depression and physical
      activity data. RESULTS: After controlling for asthma status, pulmonary
      impairment, age, poverty-to-income ratio (PIR), education, gender, marital
      status, body mass index (BMI), cotinine, comorbidity index, race-ethnicity, and
      smoking status, those who met physical activity guidelines had a 59% (odds ratio
      (OR)=0.41; 95% confidence interval (CI): 0.18-0.94) lower odds of having MDD.
      Using multivariate linear regression with depression symptoms as the outcome
      variable, and after adjustments, physical activity was inversely associated with
      depression symptoms in a dose-response manner; lowest tertile was the referent
      group, middle tertile coefficient: -1.06 (95% CI: -1.98 to -0.14), and highest
      tertile coefficient: -1.10 (95% CI: -1.84 to -0.34). CONCLUSIONS: Physical
      activity inversely associates with MDD in adults with pulmonary impairments, and
      does so in a dose-response manner. This suggests that individuals with pulmonary
      impairments should be encouraged to engage in enjoyable, safe forms of physical
      activity in a progressive manner.

PMID- 23867716
TI  - Screen for small molecules increasing the mitochondrial membrane potential.
AB  - The identification of small molecules that positively modulate the mitochondrial
      respiratory function has broad applications in fundamental research, therapeutic
      target validation, and drug discovery. We present an approach in which primary
      screens for mitochondrial function in yeast are used to efficiently identify a
      subset of high-value compounds that can in turn be rapidly tested against a broad
      range of mammalian cell lines. The ability of the yeast assay to successfully
      identify in a high-throughput format hit compounds that increase the
      mitochondrial membrane potential and adenosine triphosphate (ATP) levels by as
      little as 15% was demonstrated. In this study, 14 hits were identified from a
      collection of 13,680 compounds. Secondary testing with myotubes, fibroblasts, and
      PC-12 and HepG2 cells identified two compounds increasing ATP levels in
      hepatocytes and two other compounds increasing ATP in fibroblasts. The effect on
      hepatocytes was further studied using genomic and mitochondrial proteomic tools
      to characterize the changes induced by the two compounds. Changes in the
      accumulation of a series of factors involved in early gene response or apoptosis
      or linked to metabolic functions (i.e., beta-Klotho, RORalpha, PGC-1alpha, G6PC,
      IGFBP1, FTL) were discovered. 

PMID- 23867717
TI  - Clinical and morphological evaluation of gold micro shunt after unsuccessful
      surgical treatment of patients with primary open-angle glaucoma.
AB  - PURPOSE: To report the clinicopathologic features in a series of patients after
      ineffective glaucoma surgery with gold micro shunts (GMS) 2 years after the
      procedure. METHODS: This was an interventional case series study including two
      cases of GMS and two of GMS+ removal. Each specimen was sectioned into three
      portions: proximal, middle, and distal, and embedded into paraffin blocks, cut
      into 3 MUm sections and stained with hematoxylin and eosin and Masson's
      trichrome. In the case of inflammatory infiltrations a reaction with an LCA
      (CD45) monoclonal antibody was performed. RESULTS: Mean IOP before GMS removal
      was 28.8 +/- 4.3 mm Hg, and the patients were administered 2.3 +/- 0.5 anti
      glaucoma drugs. The progression of changes in the visual field was observed in
      all cases. In three cases different grade intensification of corneal
      decompression was observed. Colonization of the connective tissue was found in
      the channels and around the microimplant in all cases. In two cases infiltration
      was detected from giant polynuclear and mononuclear cells. CONCLUSIONS:
      Connective tissue colonization was the cause of GMS obstruction. This can be a
      non-inflammatory process, but it may also result from chronic inflammation
      occurring in the suprachoroidal space.

PMID- 23867718
TI  - The impact of the Virtual Ophthalmology Clinic on medical students' learning: a
      randomised controlled trial.
AB  - AIM: The Virtual Ophthalmology Clinic (VOC) is an interactive web-based teaching
      module, with special emphasis on history taking and clinical reasoning skills.
      The purpose of this study was to determine the impact of VOC on medical students'
      learning. METHODS: A randomised controlled trial (RCT) was conducted with medical
      students from the University of Sydney (n=188) who were randomly assigned into
      either an experimental (n=93) or a control group (n=95). A pre- and post-test and
      student satisfaction questionnaire were administered. Twelve months later a
      follow-up test was conducted to determine the long-term retention rate of
      graduates. RESULTS: There was a statistically significant (P<0.001) within
      subject improvement pre- to post rotation in the number of correctly answered
      questions for both the control and experimental groups (mean improvement for
      control 10%, 95% CI 1.3-2.6, and for experimental 17.5%, 95% CI 3.0-4.0). The
      improvement was significantly greater in the experimental group (mean difference
      in improvement between groups 7.5%, 95% CI 0.8-2.3, P<0.001). At 12 months follow
      up testing, the experimental group scored on average 1.6 (8%) (95%CI 0.4 to 2.7,
      P=0.007) higher than the controls. CONCLUSION: On the basis of a statistically
      significant improvement in academic performance and highly positive student
      feedback, the implementation of VOC may provide a means to address challenges to
      ophthalmic learning outcomes in an already crowded medical curriculum.

PMID- 23867719
TI  - A new model to perform electrophysiological studies in the early embryonic mouse
      heart.
AB  - BACKGROUND: The first electrocardiograms (ECGs) have been recorded with a
      capillary electrometer in the late 19(th) century by John Burdon Sanderson and
      Augustus Waller. In 1903 Willem Einthoven used the much more sensitive string
      galvanometer and was awarded Nobel Price in Medicine for this discovery. Though
      the physical principles of that era are still in use, there have been many
      advances but also challenges in cardiac electrophysiology over the last decades.
      One challenge is to record electrocardiograms of rather small animals such as
      mice and even smaller organisms such as their embryos. As mice belong to the most
      routinely used laboratory animals it is important to better understand their
      physiology and specific diseases. We therefore aimed to study whether it is
      feasible to measure electrical activities of embryonic mouse hearts. METHODS AND
      RESULTS: For our studies we used substrate-integrated Microelectrode Arrays
      combined with newly developed stimulation electrodes to perform
      electrophysiological studies in these hearts. The system enabled us to perform
      ECG-like recordings with atrio-ventricular (anterograde) and ventriculo-atrial
      (retrograde) stimulation. The functional separation of atria and ventricles,
      indicated by a stable atrio-ventricular conduction time, occurred clearly earlier
      than the morphological separation. Electrical stimulation induced a reversible
      prolongation of the anterograde and retrograde conduction up to atrio-ventricular
      conduction blocks at higher frequencies. CONCLUSION: These results yield new
      insight into functional aspects of murine cardiac development, and may help as a
      new diagnostic tool to uncover the functional and electrophysiological background
      of embryonic cardiac phenotypes of genetically altered mice.

PMID- 23867720
TI  - Combination therapy for subarachnoid hemorrhage--is nimodipine the wrong partner?

PMID- 23867722
TI  - Anthropometric indices predicting incident type 2 diabetes in an Iranian
      population: the Isfahan Cohort Study.
AB  - BACKGROUND: The link between adiposity and type 2 diabetes (T2D) is well known.
      However, it remains controversial as to which index and cutoff point is the best
      predictor in different populations. METHODS: A total of 2981 urban and rural
      Iranian adults over 35 years of age, and free of cardiovascular disease and
      diabetes were followed for 7 years. Anthropometric indices included body mass
      index (BMI), body adiposity index [BAI=(hip circumference/height1.5)-18], waist
      to-height ratio (WHtR), waist-to-hip ratio (WHpR), and waist and hip
      circumferences. T2D was defined as fasting plasma glucose >= 126 mg/dL or 2-h
      post-prandial plasma glucose >= 200 mg/dL, or the use of antidiabetic agents.
      Receiver operating characteristic curve analysis determined the best cutoff point
      for each adiposity index. RESULTS: After 7 years of follow-up, 389 new cases of
      diabetes were found. Most indices were linearly associated with increased risk of
      diabetes but the best continuous predictor was WHtR in men [odds ratio: 1.10 (95%
      confidence interval: 1.07-1.12) for one unit] and BMI in women [1.08 (1.04-1.11)
      for 0.1 kg/m2]. BMI cutoffs of 26 kg/m2 in men and 30 kg/m2 in women were the
      best binary predictors in adjusted models, and showed increased T2D risks of 2.91
      (2.06-4.12) and 1.94 (1.42-2.66) times, respectively. All central-obesity indices
      in men and WHpR in women were also significantly associated with T2D independent
      of BMI. BAI was significantly associated with T2D in men but not in women.
      CONCLUSION: BMI at the appropriate cutoffs in both genders and WHtR in men and
      BMI in women as continuous factors were the best predictors of incident T2D in
      this Iranian population.

PMID- 23867723
TI  - Diagnostic potential of the pulsed discharged helium ionization detector (PDHID)
      for pathogenic Mycobacterial volatile biomarkers.
AB  - Pathogenic Mycobacteria cause diseases in animals and humans with significant
      economic and societal consequences. Current methods for Mycobacterial detection
      relies upon time- and labor-intensive techniques such as culturing or DNA
      analysis. Using gas chromatography and mass spectrometry, four volatile compounds
      (methyl phenylacetate, methyl p-anisate, methyl nicotinate and o-phenyl anisole)
      were recently proposed as potential biomarkers for Mycobacteria. We demonstrate
      for the first time the capabilities of a field-deployable, pulsed discharge
      helium ionization detector (PDHID) for sensing these volatiles. We determined the
      analytical performance of the PDHID toward these Mycobacterial volatiles.
      Detector performance was moderately affected over the temperature range of 150 to
      350  degrees C. The linear dynamic range for all four analytes exceeded three
      orders of magnitude. The limits of detection (LOD) and quantitation (LOQ) were
      calculated as 150 and 450 pg respectively, for all compounds, except methyl
      phenylacetate (LOD and LOQ, 90 and 270 pg, respectively). Control charts revealed
      that the PDHID detection system was generally stable, and deviations could be
      traced to common causes and excluded special causes. Grob tests and ionization
      potential data suggest that the PDHID is capable of detecting Mycobacterial
      volatiles in a complex milieu such as culture headspace or breath samples from
      tuberculosis patients. The diagnostic potential of the PDHID is critical to our
      goal of a handheld, field-deployable 'sniffer' system for biological pathogens
      and chemical warfare agents. 

PMID- 23867721
TI  - Integrated virus-host methylome analysis in head and neck squamous cell
      carcinoma.
AB  - One in six cancers worldwide is caused by infection and human papillomavirus
      (HPV) is one of the main culprits. To better understand the dynamics of HPV
      integration and its effect on both the viral and host methylomes, we conducted
      whole-genome DNA methylation analysis using MeDIP-seq of HPV+ and HPV- head and
      neck squamous cell carcinoma (HNSCC). We determined the viral subtype to be HPV
      16 in all cases and show that HPV-16 integrates into the host genome at multiple
      random sites and that this process predominantly involves the transcriptional
      repressor gene (E2) in the viral genome. Comparative analysis identified 453 (FDR
      <= 0.01) differentially methylated regions (DMRs) in the HPV+ host methylome.
      Bioinformatics characterization of these DMRs confirmed the previously reported
      cadherin genes to be affected but also revealed new targets for HPV-mediated
      methylation changes at regions not covered by array-based platforms, including
      the recently identified super-enhancers.

PMID- 23867724
TI  - Feasibility of an endoscopic approach to the axillary nerve and the nerve to the
      long head of the triceps brachii with the help of the Da Vinci Robot.
AB  - Surgery to transfer the axillary nerve and the nerve of the long head of the
      triceps presents two obstacles: 1) the access portals are not standardized and 2)
      the nerves are for their larger part approached through large incisions. The goal
      of this study was to explore the feasibility of an endoscopic microsurgical
      approach. The posterior aspect of a cadaver shoulder was approached through three
      communicating mini-incisions. The Da Vinci robot camera was installed on a
      central trocart, and the instrument arms on the adjacent trocarts. A gas
      insufflation distended the soft tissues up to the lateral axillary space. The
      branches of the axillary nerve and the nerve to the long head of the triceps
      brachii muscle were identified. The dissection of the axillary nerve trunk and
      its branches was easy. The posterior humeral circumflex veins and artery were
      dissected as well without any difficulty. Finding the nerve to the long head of
      the triceps brachii was found to be more challenging because of its deeper
      location. Robots properties allow performing conventional microsurgery:
      elimination of the physiologic tremor and multiplication of the movements. They
      also facilitate the endoscopic approach of the peripheral nerves, as seen in our
      results on the terminal branches of the axillary nerve and the nerve to the long
      head of the triceps brachii. 

PMID- 23867726
TI  - Variation in the FADS1/2 gene cluster alters plasma n-6 PUFA and is weakly
      associated with hsCRP levels in healthy young adults.
AB  - INTRODUCTION: Past research has reported that single nucleotide polymorphisms
      (SNPs) in fatty acid desaturase 1 and 2 (FADS1/2) can influence plasma fatty acid
      (FA) profiles. Changes in FA profiles are known to influence inflammatory
      processes; therefore both FA and SNPs in FADS1/2 may affect inflammation. The
      goals of this study were to (i) examine the relationships between individual n-6
      FA and estimates of FA desaturation with circulating high sensitivity C-reactive
      protein (hsCRP) levels, and (ii) determine whether SNPs in FADS1/2 are associated
      with changes in hsCRP. METHODS: FA and hsCRP were measured in fasted plasma
      samples from 878 healthy young adults (20-29yrs). Circulating levels of plasma
      linoleic (LA), gamma-linolenic (GLA), dihomo-gamma-linolenic (DGLA) and
      arachidonic (AA) acids were measured by gas chromatography and used to calculate
      desaturase indices for FADS1/2. Nineteen SNPs in FADS1/2 were genotyped in all
      subjects and six (rs174579, rs174593, rs174626, rs526126, rs968567 and
      rs17831757) were further analyzed. RESULTS: Significant inverse associations were
      found between LA and hsCRP (p=8.55*10(-9)) and the FADS1 desaturase index and
      hsCRP (p=4.41*10(-6)). A significant positive association was found between DGLA
      and hsCRP (p=9.10*10(-11)). Several SNPs were associated with circulating levels
      of individual FA and desaturase indices, with minor allele carriers having lower
      AA levels and reduced desaturase indices. A single SNP in FADS2 (rs526126) was
      weakly associated with hsCRP (p=0.05). CONCLUSIONS: This study highlights the
      relationships between FA and hsCRP, and confirms that FA are strongly influenced
      by SNPs in FADS1/2. Furthermore, we found weak evidence that SNPs in FADS1/2 may
      influence hsCRP levels in young adults.

PMID- 23867725
TI  - Global DNA methylation in a population with aflatoxin B1 exposure.
AB  - We previously reported that global DNA hypomethylation, measured as Sat2
      methylation in white blood cells (WBC), and aflatoxin B1 (AFB1) exposure were
      associated with increased hepatocellular carcinoma risk. In this study, we
      assessed the association between AFB1 exposure and global DNA methylation. We
      measured LINE-1 and Sat2 methylation in WBC DNA samples from 1140 cancer free
      participants of the Cancer Screening Program (CSP) cohort. Blood and urine
      samples were used to determine the level of AFB1-albumin (AFB1-Alb) adducts and
      urinary AFB1 metabolites. In continuous models, we found reverse associations of
      urinary AFB1 with LINE-1 and Sat2 methylation. The odds ratio (OR) per 1 unit
      decrease were 1.12 (95%CI = 1.03-1.22) for LINE-1 and 1.48 (95%CI = 1.10-2.00)
      for Sat2 methylation. When compared with subjects in the highest quartile of LINE
      1, we found that individuals in the 2nd and 3rd quartiles were less likely to
      have detectable AFB1-Alb adducts, with ORs (95%CI) of 0.61 (0.40-0.93), 0.61
      (0.40-.94), and 1.09 (0.69-1.72), respectively. The OR for detectable AFB1-Alb
      was 1.81 (95%CI = 1.15-2.85) for subjects in the lowest quartile of Sat2
      methylation. The OR for detection of urinary AFB1 for those with LINE-1
      methylation in the lowest quartile compared with those in the highest quartile
      was 1.87 (95%CI = 1.15-3.04). The corresponding OR was 1.75 (95%CI = 1.08-2.82)
      for subjects in the lowest quartile of Sat2 methylation. The association between
      AFB1 exposure and global DNA methylation may have implications for the epigenetic
      effect of AFB1 on hepatocellular carcinoma development and also suggests that
      changes in DNA methylation may represent an epigenetic biomarker of dietary AFB1
      exposure.

PMID- 23867727
TI  - The effect of fatty acid positioning in dietary triacylglycerols and intake of
      long-chain n-3 polyunsaturated fatty acids on bone mineral accretion in growing
      piglets.
AB  - Long-chain n-3 PUFA (LCPUFA) and palmitate (16:0) positioning in the
      triacylglycerol (TAG) of infant formula may affect calcium-uptake which could
      affect bone health. We investigated if a human milk fat substitute (HMFS) with a
      modified TAG structure holding 16:0 predominantly in the sn-2-position compared
      with a control (CONT) and if increasing n-3LCPUFA intake giving fish oil (FO)
      compared with sunflower oil (SO) would affect bone parameters in piglets in two
      sets of controlled 14d-interventions (n=12/group). We assessed this by dual
      energy x-ray absorptiometry, and ex vivo peripheral quantitative computed
      tomography and mechanical strength. Bone mineral content (BMC) was higher in the
      FO compared to the SO-group (p=0.03). Despite similar weight gain in HMFS- and
      CONT-groups, body fat accumulation was higher with HMFS (p<0.001), and BMC, bone
      area (BA) and cortical BA in femur were lower (p=0.002, p=0.005, and p=0.02,
      respectively), indicating importance of both n-3LCPUFA and 16:0 TAG-positioning
      in infant formulas.

PMID- 23867728
TI  - T7 peptide-functionalized nanoparticles utilizing RNA interference for glioma
      dual targeting.
AB  - Among all the malignant brain tumors, glioma is the deadliest and most common
      form with poor prognosis. Gene therapy is regarded as a promising way to halt the
      progress of the disease or even cure the tumor and RNA interference (RNAi) stands
      out. However, the existence of the blood-brain barrier (BBB) and blood tumor
      barrier (BTB) limits the delivery of these therapeutic genes. In this work, the
      delivery system targeting to the transferrin (Tf) receptor highly expressed on
      both BBB and glioma was successfully synthesized and would not compete with
      endogenous Tf. U87 cells stably express luciferase were employed here to simulate
      tumor and the RNAi experiments in vitro and in vivo validated that the gene
      silencing activity was 2.17-fold higher with the targeting ligand modification.
      The dual-targeting gene delivery system exhibits a series of advantages, such as
      high efficiency, low toxicity, stability and high transaction efficiency, which
      may provide new opportunities in RNAi therapeutics and nanomedicine of brain
      tumors. 

PMID- 23867729
TI  - Repeated intramuscular injections of nerve growth factor induced progressive
      muscle hyperalgesia, facilitated temporal summation, and expanded pain areas.
AB  - Intramuscular injection of nerve growth factor (NGF) is known to induce deep
      tissue mechanical hyperalgesia. In this study it was hypothesised that daily
      intramuscular injections of NGF produce a progressive manifestation of soreness,
      mechanical hyperalgesia, and temporal summation of pain. In a double-blind
      placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF
      into the tibialis anterior muscle and with isotonic saline on the contralateral
      side. Assessments were performed before and after the injections on days 0, 1,
      and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was
      assessed on a Likert scale. Computer-controlled pressure algometry was used to
      assess the pressure pain thresholds (PPTs). Temporal summation of pain after
      repeated pressure stimulations was assessed by computer-controlled pressure
      algometry. The pain distribution following painful pressure stimulation was also
      recorded. Compared with baseline and isotonic saline, the NGF injections caused
      (P<0.05): (1) progressively increasing soreness scores from 3 hours after the
      first injection until day 2, after which it remained increased; (2) decreased
      PPTs at days 1 to 3; (3) facilitated temporal summation of pressure pain at days
      1 to 10; and (4) enlarged pressure-induced pain area after the injection on day 1
      to day 6. The daily injections of NGF produced a progressive manifestation of
      muscle soreness, mechanical hyperalgesia, temporal summation of pressure pain,
      and pressure-induced pain distribution. These data illustrate that the prolonged
      NGF application affects peripheral and central mechanisms and may reflect process
      in musculoskeletal pain conditions.

PMID- 23867731
TI  - Do various baseline characteristics of transversus abdominis and lumbar
      multifidus predict clinical outcomes in nonspecific low back pain? A systematic
      review.
AB  - Although individual reports suggest that baseline morphometry or activity of
      transversus abdominis or lumbar multifidus predict clinical outcome of low back
      pain (LBP), a related systematic review is unavailable. Therefore, this review
      summarized evidence regarding the predictive value of these muscular
      characteristics. Candidate publications were identified from 6 electronic medical
      databases. After review, 5 cohort studies were included. Although this review
      intended to encompass studies using different muscle assessment methods, all
      included studies coincidentally used ultrasound imaging. No research investigated
      the relation between static morphometry and clinical outcomes. Evidence synthesis
      showed limited evidence supporting poor baseline transversus abdominis
      contraction thickness ratio as a treatment effect modifier favoring motor control
      exercise. Limited evidence supported that high baseline transversus abdominis
      lateral slide was associated with higher pain intensity after various exercise
      interventions at 1-year follow-up. However, there was limited evidence for the
      absence of relation between the contraction thickness ratio of transversus
      abdominis or anticipatory onset of lateral abdominal muscles at baseline and the
      short- or long-term LBP intensity after exercise interventions. There was
      conflicting evidence for a relation between baseline percent thickness change of
      lumbar multifidus during contraction and the clinical outcomes of patients after
      various conservative treatments. Given study heterogeneity, the small number of
      included studies and the inability of conventional greyscale B-mode ultrasound
      imaging to measure muscle activity, our findings should be interpreted with
      caution. Further large-scale prospective studies that use appropriate technology
      (ie, electromyography to assess muscle activity) should be conducted to
      investigate the predictive value of morphometry or activity of these muscles with
      respect to LBP-related outcomes measures. 

PMID- 23867730
TI  - Oxidized linoleic acid metabolite-cytochrome P450 system (OLAM-CYP) is active in
      biopsy samples from patients with inflammatory dental pain.
AB  - Endogenous TRPV1 agonists such as oxidized linoleic acid metabolites (OLAMs) and
      the enzymes releasing them [eg, cytochrome P450 (CYP)] are up-regulated after
      inflammation in the rat. However, it is not known whether such agonists are
      elevated in human inflammatory pain conditions. Because TRPV1 is expressed in
      human dental pulp nociceptors, we hypothesized that OLAM-CYP machinery is active
      in this tissue type and is increased under painful inflammatory conditions such
      as irreversible pulpitis (IP). The aim of this study was to compare CYP
      expression and linoleic acid (LA) metabolism in normal vs inflamed human dental
      pulp. Our data showed that exogenous LA metabolism was significantly increased in
      IP tissues compared to normal tissues and that pretreatment with a CYP inhibitor,
      ketoconazole, significantly inhibited LA metabolism. Additionally, extracts
      obtained from LA-treated inflamed tissues evoked significant inward currents in
      trigeminal ganglia neurons and were blocked by pretreatment with the TRPV1
      antagonist IRTX. Moreover, extracts obtained from ketoconazole-pretreated
      inflamed tissues significantly reduced inward currents in trigeminal ganglia
      neurons. These data suggest that LA metabolites produced in human inflamed
      tissues act as TRPV1 agonists and that the metabolite production can be targeted
      by CYP inhibition. In addition, immunohistochemical analysis of 2 CYP isoforms,
      CYP2J and CYP3A1, were shown to be predominately expressed in immune cells
      infiltrating the inflamed dental pulp, emphasizing the paracrine role of CYP
      enzymes in OLAM regulation. Collectively, our data indicate that the machinery
      responsible for OLAM production is up-regulated during inflammation and can be
      targeted to develop potential analgesics for inflammatory-induced dental pain. 

PMID- 23867732
TI  - Facial pain with localized and widespread manifestations: separate pathways of
      vulnerability.
AB  - Human association studies of common genetic polymorphisms have identified many
      loci that are associated with risk of complex diseases, although individual loci
      typically have small effects. However, by envisaging genetic associations in
      terms of cellular pathways, rather than any specific polymorphism, combined
      effects of many biologically relevant alleles can be detected. The effects are
      likely to be most apparent in investigations of phenotypically homogenous
      subtypes of complex diseases. We report findings from a case-control, genetic
      association study of relationships between 2925 single nucleotide polymorphisms
      (SNPs) and 2 subtypes of a commonly occurring chronic facial pain condition,
      temporomandibular disorder (TMD): 1) localized TMD and 2) TMD with widespread
      pain. When compared to healthy controls, cases with localized TMD differed in
      allelic frequency of SNPs that mapped to a serotonergic receptor pathway
      (P=0.0012), while cases of TMD with widespread pain differed in allelic frequency
      of SNPs that mapped to a T-cell receptor pathway (P=0.0014). A risk index
      representing combined effects of 6 SNPs from the serotonergic pathway was
      associated with greater odds of localized TMD (odds ratio 2.7, P=1.3 E-09), and
      the result was reproduced in a replication case-control cohort study of 639
      people (odds ratio 1.6, P=0.014). A risk index representing combined effects of 8
      SNPs from the T-cell receptor pathway was associated with greater odds of TMD
      with widespread pain (P=1.9 E-08), although the result was not significant in the
      replication cohort. These findings illustrate potential for clinical
      classification of chronic pain based on distinct molecular profiles and genetic
      background. 

PMID- 23867733
TI  - Neural mechanisms mediating positive and negative treatment expectations in
      visceral pain: a functional magnetic resonance imaging study on placebo and
      nocebo effects in healthy volunteers.
AB  - To elucidate placebo and nocebo effects in visceral pain, we conducted a
      functional magnetic resonance imaging (fMRI) study to analyze effects of positive
      and negative treatment expectations in a rectal pain model. In 36 healthy
      volunteers, painful rectal distensions were delivered after intravenous
      application of an inert substance combined with either positive instructions of
      pain relief (placebo group) or negative instructions of pain increase (nocebo
      group), each compared to neutral instructions. Neural activation during cued-pain
      anticipation and pain was analyzed along with expected and perceived pain
      intensity. Expected and perceived pain intensity were significantly increased in
      the nocebo group and significantly decreased in the placebo group. In the placebo
      group, positive expectations significantly reduced activation of the
      somatosensory cortex during anticipation and of the insula, somatosensory cortex,
      and amygdala during pain delivery when compared to neutral expectations. Within
      the nocebo group, negative expectations led to significantly increased insula
      activation during painful stimulation. Direct group contrasts during expectation
      modulation revealed significantly increased distension-induced activation within
      the somatosensory cortex in the nocebo group. In conclusion, the experience and
      neural processing of visceral pain can be increased or decreased by drug-specific
      expectations. This first brain imaging study on nocebo effects in visceral pain
      has implications for the pathophysiology and treatment of patients with chronic
      abdominal complaints such as irritable bowel syndrome. 

PMID- 23867734
TI  - Wound-healing growth factor, basic FGF, induces Erk1/2-dependent mechanical
      hyperalgesia.
AB  - Growth factors such as nerve growth factor and glial cell line-derived
      neurotrophic factor are known to induce pain sensitization. However, a plethora
      of other growth factors is released during inflammation and tissue regeneration,
      and many of them are essential for wound healing. Which wound-healing factors
      also alter the sensitivity of nociceptive neurons is not well known. We studied
      the wound-healing factor, basic fibroblast growth factor (bFGF), for its role in
      pain sensitization. Reverse transcription polymerase chain reaction showed that
      the receptor of bFGF, FGFR1, is expressed in lumbar rat dorsal root ganglia
      (DRG). We demonstrated presence of FGFR1 protein in DRG neurons by a recently
      introduced quantitative automated immunofluorescent microscopic technique. FGFR1
      was expressed in all lumbar DRG neurons as quantified by mixture modeling.
      Corroborating the mRNA and protein expression data, bFGF induced Erk1/2
      phosphorylation in nociceptive neurons, which could be blocked by inhibition of
      FGF receptors. Furthermore, bFGF activated Erk1/2 in a dose- and time-dependent
      manner. Using single-cell electrophysiological recordings, we found that bFGF
      treatment of DRG neurons increased the current-density of NaV1.8 channels. Erk1/2
      inhibitors abrogated this increase. Importantly, intradermal injection of bFGF in
      rats induced Erk1/2-dependent mechanical hyperalgesia. PERSPECTIVE: Analyzing
      intracellular signaling dynamics in nociceptive neurons has proven to be a
      powerful approach to identify novel modulators of pain. In addition to describing
      a new sensitizing factor, our findings indicate the potential to investigate
      wound-healing factors for their role in nociception.

PMID- 23867735
TI  - Changes in sensory activity of ocular surface sensory nerves during allergic
      keratoconjunctivitis.
AB  - Peripheral neural mechanisms underlying the sensations of irritation, discomfort,
      and itch accompanying the eye allergic response have not been hitherto analyzed.
      We explored this question recording the changes in the electrical activity of
      corneoconjunctival sensory nerve fibers of the guinea pig after an ocular
      allergic challenge. Sensitization was produced by i.p. ovalbumin followed by
      repeated application in the eye of 10% ovalbumin on days 14 to 18. Blinking and
      tearing rate were measured. Spontaneous and stimulus-evoked (mechanical, thermal,
      chemical) impulse activity was recorded from mechanonociceptor, polymodal
      nociceptor and cold corneoscleral sensory afferent fibers. After a single (day
      14) or repeated daily exposures to the allergen during the following 3 to 4days,
      tearing and blinking rate increased significantly. Also, sensitization was
      observed in mechanonociceptors (transient reduction of mechanical threshold only
      on day 14) and in polymodal nociceptors (sustained enhancement of the impulse
      response to acidic stimulation). In contrast, cold thermoreceptors showed a
      significant decrease in basal ongoing activity and in the response to cooling.
      Treatment with the TRPV1 and TRPA1 blockers capsazepine and HC-030031 reversed
      the augmented blinking. Only capsazepine attenuated tearing rate increase and
      sensitization of the polymodal nociceptors response to CO2. Capsazepine also
      prevented the decrease in cold thermoreceptor activity caused by the allergic
      challenge. We conclude that changes in nerve impulse activity accompanying the
      ocular allergic response, primarily mediated by activation of nociceptor's TRPV1
      and to a lesser degree by activation of TRPA1 channels, explain the eye
      discomfort sensations accompanying allergic episodes. 

PMID- 23867737
TI  - Emotional distraction in boys with ADHD: neural and behavioral correlates.
AB  - Although, in everyday life, patients with attention deficit hyperactivity
      disorder (ADHD) are frequently distracted by goal-irrelevant affective stimuli,
      little is known about the neural and behavioral substrates underlying this
      emotional distractibility. Because some of the most important brain responses
      associated with the sudden onset of an emotional distracter are characterized by
      their early latency onset and short duration, we addressed this issue by using a
      temporally agile neural signal capable of detecting and distinguishing them.
      Specifically, scalp event-related potentials (ERPs) were recorded while 20 boys
      with ADHD combined type and 20 healthy comparison subjects performed a digit
      categorization task during the presentation of three types of irrelevant,
      distracting stimuli: arousing negative (A-), neutral (N) and arousing positive
      (A+). Behavioral data showed that emotional distracters (both A- and A+) were
      associated with longer reaction times than neutral ones in the ADHD group,
      whereas no differences were found in the control group. ERP data revealed that,
      compared with control subjects, boys with ADHD showed larger anterior N2
      amplitudes for emotional than for neutral distracters. Furthermore, regression
      analyses between ERP data and subjects' emotional ratings of distracting stimuli
      showed that only in the ADHD group, emotional arousal (ranging from calming to
      arousing) was associated with anterior N2: its amplitude increased as the arousal
      content of the visual distracter increased. These results suggest that boys with
      ADHD are more vulnerable to the distracting effects of irrelevant emotional
      stimuli than control subjects. The present study provides first data on the
      neural substrates underlying emotional distractibility in ADHD. 

PMID- 23867736
TI  - Differential roles of the frontal and parietal cortices in the control of
      saccades.
AB  - Although externally as well as internally-guided eye movements allow us to
      flexibly explore the visual environment, their differential neural mechanisms
      remain elusive. A better understanding of these neural mechanisms will help us to
      understand the control of action and to elucidate the nature of cognitive
      deficits in certain psychiatric populations (e.g., schizophrenia) that show
      increased latencies in volitional but not visually-guided saccades. Both the
      superior precentral sulcus (sPCS) and the intraparietal sulcus (IPS) are
      implicated in the control of eye movements. However, it remains unknown what
      differential contributions the two areas make to the programming of visually
      guided and internally-guided saccades. In this study we tested the hypotheses
      that sPCS and IPS distinctly encode internally-guided saccades and visually
      guided saccades. We scanned subjects with fMRI while they generated visually
      guided and internally-guided delayed saccades. We used multi-voxel pattern
      analysis to test whether patterns of cue related, preparatory and saccade related
      activation could be used to predict the direction of the planned eye movement.
      Results indicate that patterns in the human sPCS predicted internally-guided
      saccades but not visually-guided saccades in all trial periods and patterns in
      the IPS predicted internally-guided saccades and visually-guided saccades equally
      well. The results support the hypothesis that the human sPCS and IPS make
      distinct contributions to the control of volitional eye movements.

PMID- 23867738
TI  - Cognitive consequences of individual differences in arousal asymmetry.
AB  - Prior research has demonstrated that semantic organization in the right
      hemisphere (RH) is more diffuse and specialized for distant semantic associates
      than is semantic organization in the left hemisphere (LH). The present research
      explored individual differences in this regard. If the RH is more specialized for
      distant semantic associates, then individuals with a more active RH should
      display greater activation of distant semantic associations. Two experiments were
      conducted to examine this issue. In both studies a line bisection task was used
      to assess arousal asymmetry. In Experiment 1, greater RH activation was
      associated with the ability to generate remote associates to three word stimuli.
      In Experiment 2, relatively greater RH activation was associated with enhanced
      priming of distant semantic associates. Taken together, these experiments
      demonstrate that arousal asymmetry is an individual difference variable that is
      related to variability in semantic organization and retrieval. 

PMID- 23867739
TI  - Proactive and reactive sequential effects on selective attention.
AB  - Sequences of events can affect selective attention either through proactive
      mechanisms, through reactive mechanisms, or through a combination of the two. The
      current study examined electrophysiological responses to both prime and target
      stimuli in a primed dichotic listening task. Each trial presented a distractor
      prime syllable followed by two simultaneous syllables, and participants were
      asked to report one of the simultaneous syllables. Trials where the participant
      reported the non-primed syllable showed more negative event-related potentials at
      prime presentation, which may indicate inhibition of the prime representation.
      Trials where the participant reported the primed syllable showed more negative
      event-related potentials at target presentation, which may indicate cognitive
      conflict and effortful response selection. In context of current theories, the
      data suggest that the interplay of a proactive inhibition bias and a reactive
      potential for conflict is involved in causing sequential effects on selective
      attention mechanisms. 

PMID- 23867742
TI  - Metal oxide gas sensor drift compensation using a dynamic classifier ensemble
      based on fitting.
AB  - Sensor drift is currently the most challenging problem in gas sensing. We propose
      a novel ensemble method with dynamic weights based on fitting (DWF) to solve the
      gas discrimination problem, regardless of the gas concentration, with high
      accuracy over extended periods of time. The DWF method uses a dynamic weighted
      combination of support vector machine (SVM) classifiers trained by the datasets
      that are collected at different time periods. In the testing of future datasets,
      the classifier weights are predicted by fitting functions, which are obtained by
      the proper fitting of the optimal weights during training. We compare the
      performance of the DWF method with that of competing methods in an experiment
      based on a public dataset that was compiled over a period of three years. The
      experimental results demonstrate that the DWF method outperforms the other
      methods considered. Furthermore, the DWF method can be further optimized by
      applying a fitting function that more closely matches the variation of the
      optimal weight over time. 

PMID- 23867743
TI  - Piezoelectric driving of vibration conveyors: an experimental assessment.
AB  - Vibratory feeders or vibratory conveyors have been widely used for the transport
      and orientation of individual parts and bulk materials in many branches of
      industrial activity. From the designer's standpoint, the current endeavor is to
      conceive efficient vibratory feeders, satisfying constraints of power
      consumption, vibration transmission and noise emission. Moreover, the interest in
      the reduction of maintenance cost is always present. In this context, this paper
      investigates experimentally the concept of vibratory conveying based on the use
      of piezoelectric materials for motion generation. A small-size prototype of a
      linear conveyor, in which lead-zirconate-titanate (PZT) patches are bonded to the
      resilient elements, is described. One of the main design goals is that the
      prototype is intended to be fed directly from the electric network, aiming at
      avoiding the use of electronic equipment for driving. To comply with this feature
      and, at the same time, enable to adjust the transport velocity, a mechanical
      device has been conceived in such a way that the first natural frequency of the
      conveyor can be changed. It is shown that the transport velocity is determined by
      the proximity between the excitation frequency and the first natural frequency of
      the conveyor. The experimental tests performed to characterize the dynamic
      behavior of the prototype are described and the range of transport velocities is
      determined. 

PMID- 23867744
TI  - Optimal placement of accelerometers for the detection of everyday activities.
AB  - This article describes an investigation to determine the optimal placement of
      accelerometers for the purpose of detecting a range of everyday activities. The
      paper investigates the effect of combining data from accelerometers placed at
      various bodily locations on the accuracy of activity detection. Eight healthy
      males participated within the study. Data were collected from six wireless tri
      axial accelerometers placed at the chest, wrist, lower back, hip, thigh and foot.
      Activities included walking, running on a motorized treadmill, sitting, lying,
      standing and walking up and down stairs. The Support Vector Machine provided the
      most accurate detection of activities of all the machine learning algorithms
      investigated. Although data from all locations provided similar levels of
      accuracy, the hip was the best single location to record data for activity
      detection using a Support Vector Machine, providing small but significantly
      better accuracy than the other investigated locations. Increasing the number of
      sensing locations from one to two or more statistically increased the accuracy of
      classification. There was no significant difference in accuracy when using two or
      more sensors. It was noted, however, that the difference in activity detection
      using single or multiple accelerometers may be more pronounced when trying to
      detect finer grain activities. Future work shall therefore investigate the
      effects of accelerometer placement on a larger range of these activities. 

PMID- 23867745
TI  - Investigation on dynamic calibration for an optical-fiber solids concentration
      probe in gas-solid two-phase flows.
AB  - This paper presents a review and analysis of the research that has been carried
      out on dynamic calibration for optical-fiber solids concentration probes. An
      introduction to the optical-fiber solids concentration probe was given. Different
      calibration methods of optical-fiber solids concentration probes reported in the
      literature were reviewed. In addition, a reflection-type optical-fiber solids
      concentration probe was uniquely calibrated at nearly full range of the solids
      concentration from 0 to packed bed concentration. The effects of particle
      properties (particle size, sphericity and color) on the calibration results were
      comprehensively investigated. The results show that the output voltage has a
      tendency to increase with the decreasing particle size, and the effect of
      particle color on calibration result is more predominant than that of sphericity.

PMID- 23867746
TI  - Parallel Hough Transform-based straight line detection and its FPGA
      implementation in embedded vision.
AB  - Hough Transform has been widely used for straight line detection in low
      definition and still images, but it suffers from execution time and resource
      requirements. Field Programmable Gate Arrays (FPGA) provide a competitive
      alternative for hardware acceleration to reap tremendous computing performance.
      In this paper, we propose a novel parallel Hough Transform (PHT) and FPGA
      architecture-associated framework for real-time straight line detection in high
      definition videos. A resource-optimized Canny edge detection method with enhanced
      non-maximum suppression conditions is presented to suppress most possible false
      edges and obtain more accurate candidate edge pixels for subsequent accelerated
      computation. Then, a novel PHT algorithm exploiting spatial angle-level
      parallelism is proposed to upgrade computational accuracy by improving the
      minimum computational step. Moreover, the FPGA based multi-level pipelined PHT
      architecture optimized by spatial parallelism ensures real-time computation for
      1,024 * 768 resolution videos without any off-chip memory consumption. This
      framework is evaluated on ALTERA DE2-115 FPGA evaluation platform at a maximum
      frequency of 200 MHz, and it can calculate straight line parameters in 15.59 ms
      on the average for one frame. Qualitative and quantitative evaluation results
      have validated the system performance regarding data throughput, memory
      bandwidth, resource, speed and robustness. 

PMID- 23867747
TI  - Histone signature of metanephric mesenchyme cell lines.
AB  - The metanephric mesenchyme (MM) gives rise to nephrons, the filtering units of
      the mature kidney. The MM is composed of uninduced (Six2(high)/Lhx1(low)) and
      induced (Wnt-stimulated, Six2(low)/Lhx1(high)) cells. The global epigenetic state
      of MM cells is unknown, partly due to technical difficulty in isolating
      sufficient numbers of homogenous cell populations. We therefore took advantage of
      two mouse clonal cell lines representing the uninduced (mK3) and induced (mK4)
      metanephric mesenchyme (based on gene expression profiles and ability to induce
      branching of ureteric bud). ChIP-Seq revealed that whereas H3K4me3 active region
      "peaks" are enriched in metabolic genes, H3K27me3 peaks decorate mesenchyme and
      epithelial cell fate commitment genes. In uninduced mK3 cells, promoters of
      "stemness" genes (e.g., Six2, Osr1) are enriched with H3K4me3 peaks; these are
      lost in induced mK4 cells. ChIP-qPCR confirmed this finding and further
      demonstrated that G9a/H3K9me2 occupy the promoter region of Six2 in induced
      cells, consistent with the inactive state of transcription. Conversely, genes
      that mark the induced epithelialized state (e.g., Lhx1, Pax8), transition from a
      non-permissive to an active chromatin signature in mK3 vs. mK4 cells,
      respectively. Importantly, stimulation of Wnt signaling in uninduced mK3 cells
      provokes an active chromatin state (high H3K4me3, low H3K27me3), recruitment of
      beta-catenin, and loss of pre-bound histone methyltransferase Ezh2 in silent
      induced genes followed by activation of transcription. We conclude that the
      chromatin signature of uninduced and induced cells correlates strongly with their
      gene expression states, suggesting a role of chromatin-based mechanisms in MM
      cell fate.

PMID- 23867748
TI  - Comparison of the physical characteristics of chlorosomes from three different
      phyla of green phototrophic bacteria.
AB  - Chlorosomes, the major antenna complexes in green sulphur bacteria, filamentous
      anoxygenic phototrophs, and phototrophic acidobacteria, are attached to the
      cytoplasmic side of the inner cell membrane and contain thousands of
      bacteriochlorophyll (BChl) molecules that harvest light and channel the energy to
      membrane-bound reaction centres. Chlorosomes from phototrophs representing three
      different phyla, Chloroflexus (Cfx.) aurantiacus, Chlorobaculum (Cba.) tepidum
      and the newly discovered "Candidatus (Ca.) Chloracidobacterium (Cab.)
      thermophilum" were analysed using PeakForce Tapping atomic force microscopy (PFT
      AFM). Gentle PFT-AFM imaging in buffered solutions that maintained the
      chlorosomes in a near-native state revealed ellipsoids of variable size, with
      surface bumps and undulations that differ between individual chlorosomes. Cba.
      tepidum chlorosomes were the largest (133*57*36nm; 141,000nm(3) volume), compared
      with chlorosomes from Cfx. aurantiacus (120*44*30nm; 84,000nm(3)) and Ca. Cab.
      thermophilum (99*40*31nm; 65,000nm(3)). Reflecting the contributions of thousands
      of pigment-pigment stacking interactions to the stability of these supramolecular
      assemblies, analysis by nanomechanical mapping shows that chlorosomes are highly
      stable and that their integrity is disrupted only by very strong forces of 1000
      2000pN. AFM topographs of Ca. Cab. thermophilum chlorosomes that had retained
      their attachment to the cytoplasmic membrane showed that this membrane
      dynamically changes shape and is composed of protrusions of up to 30nm wide and
      6nm above the mica support, possibly representing different protein domains.
      Spectral imaging revealed significant heterogeneity in the fluorescence emission
      of individual chlorosomes, likely reflecting the variations in BChl c homolog
      composition and internal arrangements of the stacked BChls within each
      chlorosome. 

PMID- 23867749
TI  - Medical management adherence as an outcome of genetic counseling in a pediatric
      setting.
AB  - PURPOSE: We sought to determine whether the inclusion of a genetic counselor in
      an initial pediatric genetics visit had an impact on patient adherence to
      management recommendations, as compared with initial visits in which only
      genetics physicians were involved. METHODS: This chart review included 198
      pediatric patients seen for their initial visit to the general genetics clinic at
      the Cincinnati Children's Hospital Medical Center in 2008. Ninety-eight patients
      were seen by one or more genetics physicians (the non-genetic counselor group),
      and 100 patients were seen by a geneticist and a genetic counselor (the genetic
      counselor group). Medical management recommendations and evidence of adherence to
      recommendations were abstracted from the medical record; adherence rates were
      compared between the genetic counselor and non-genetic counselor groups. RESULTS:
      Adherence was significantly associated with the inclusion of a genetic counselor
      (P = 0.009). Although type of management recommendation had a large impact on
      adherence, involvement of a genetic counselor significantly improved adherence in
      all three management recommendation categories. CONCLUSION: Involvement of a
      genetic counselor during an initial pediatric genetics visit may be associated
      with increased patient adherence. Further research is needed to determine whether
      this association applies in other genetic counseling settings and whether
      enhanced adherence results in improved medical outcomes.

PMID- 23867750
TI  - Investigation of the inhibitory effects of the benzodiazepine derivative, 5-BDBD
      on P2X4 purinergic receptors by two complementary methods.
AB  - BACKGROUND/AIMS: ATP-gated P2X4 purinergic receptors (P2X4Rs) are cation channels
      with important roles in diverse cell types. To date, lack of specific inhibitors
      has hampered investigations on P2X4Rs. Recently, the benzodiazepine derivative, 5
      BDBD has been proposed to selectively inhibit P2X4Rs. However, limited evidences
      are currently available on its inhibitory properties. Thus, we aimed to
      characterize the inhibitory effects of 5-BDBD on recombinant human P2X4Rs.
      METHODS: We investigated ATP-induced intracellular Ca(2+) signals and whole cell
      ion currents in HEK 293 cells that were either transiently or stably transfected
      with hP2X4Rs. RESULTS: Our data show that ATP (< 1 MUM) stimulates P2X4R-mediated
      Ca(2+) influx while endogenously expressed P2Y receptors are not activated to any
      significant extent. Both 5-BDBD and TNP-ATP inhibit ATP-induced Ca(2+) signals
      and inward ion currents in a concentration-dependent manner. Application of two
      different concentrations of 5-BDBD causes a rightward shift in ATP dose-response
      curve. Since the magnitude of maximal stimulation does not change, these data
      suggest that 5-BDBD may competitively inhibit the P2X4Rs. CONCLUSIONS: Our
      results demonstrate that application of submicromolar ATP concentrations allows
      reliable assessment of recombinant P2XR functions in HEK 293 cells. Furthermore,
      5-BDBD and TNP-ATP have similar inhibitory potencies on the P2X4Rs although their
      mechanisms of actions are different.

PMID- 23867751
TI  - Validating a breath collection and analysis system for the new tuberculosis
      breath test.
AB  - Mycobacterium tuberculosis releases four volatile compounds, methyl phenyl
      acetate, methyl nicotinate, methyl p-anisate and o-phenylanisole, some of which
      we have previously been reported to be detected in the breath of tuberculosis
      patients (Syhre et al 2009 Tuberculosis 89 263-6). These volatiles have the
      potential to offer a non-invasive and sensitive breath test for the detection of
      tuberculosis infection. To determine the best sample collection and pre
      concentration system a number of variables were examined. The four markers were
      most stable when breath was collected in a salinized glass sampling bulb compared
      to either Tedlar(r) TA, Supel(TM) Inert Foil or Supel(TM) Inert Gas bags.
      Concentration of breath onto thermal desorption cartridges indicated that
      Tenax(r) TA was the most universal sorbent for the collection of all four
      volatiles. Increasing the number of breath exhalations captured and analysed
      actively increased the detectable level of volatiles. The most important
      discovery was samples of methyl nicotinate, methyl p-anisate and o-phenylanisole
      remained stable on Tenax(r) TA cartridges for over two months at various
      altitudes. 

PMID- 23867752
TI  - Calcium transport in gill cells of Ucides cordatus, a mangrove crab living in
      variable salinity environments.
AB  - Crustaceans show discontinuous growth and have been used as a model system for
      studying cellular mechanisms of calcium transport, which is the main mineral
      found in their exoskeleton. Ucides cordatus, a mangrove crab, is naturally
      exposed to fluctuations in calcium and salinity. To study calcium transport in
      this species during isosmotic conditions, dissociated gill cells were marked with
      fluo-3 and intracellular Ca(2+) change was followed by adding extracellular
      Ca(2+) as CaCl2 (0, 0.1, 0.25, 0.50, 1.0 and 5mM), together with different
      inhibitors. For control gill cells, Ca(2+) transport followed Michaelis-Menten
      kinetics with Vmax=0.137+/-0.001 ?Ca(2+)i (MUM*22.10(4)cells(-1)*180s(-1); N=4;
      r(2)=0.99); Km=0.989+/-0.027mM. The use of different inhibitors for gill cells
      showed that amiloride (Na(+)/Ca(2+) exchange inhibitor) inhibited 80% of Ca(2+)
      transport in gill cells (Vmax). KB-R, an inhibitor of Ca influx in vertebrates,
      similarly caused a decrease in Ca(2+) transport and verapamil (Ca(2+) channel
      inhibitor) had no effect on Ca(2+) transport, while nifedipine (another Ca(2+)
      channel inhibitor) caused a 20% decrease in Ca(2+) affinity compared to control
      values. Ouabain, on the other hand, caused no change in Ca(2+) transport, while
      vanadate increased the concentration of intracellular calcium through inhibition
      of Ca(2+) efflux probably through the plasma membrane Ca(2+)-ATPase. Results show
      that transport kinetics for Ca(2+) in these crabs under isosmotic conditions is
      lower compared to a hyper-regulator freshwater crab Dilocarcinus pagei studied
      earlier using fluorescent Ca(2+) probes. These kinds of studies will help
      understanding the comparative mechanisms underlying the evolution of Ca transport
      in crabs living in different environments. 

PMID- 23867753
TI  - Adaptation of the health literacy universal precautions toolkit for rheumatology
      and cardiology - applications for pharmacy professionals to improve self
      management and outcomes in patients with chronic disease.
AB  - Over a decade of research in health literacy has provided evidence of strong
      links between literacy skills of patients and health outcomes. At the same time,
      numerous studies have yielded insight into efficacious action that health
      providers can take to mitigate the negative effects of limited literacy. This
      small study focuses on the adaptation, review and use of two new health literacy
      toolkits for health professionals who work with patients with two of the most
      prevalent chronic conditions, arthritis and cardiovascular disease. Pharmacists
      have a key role in communicating with patients and caregivers about various
      aspects of disease self-management, which frequently includes appropriate use of
      medications. Participating pharmacists and staff offered suggestions that helped
      shape revisions and reported positive experiences with brown bag events,
      suggestions for approaches with patients managing chronic diseases, and with
      concrete examples related to several medicines [such as Warfarin((c))] as well as
      to common problems [such as inability to afford needed medicine]. Although not
      yet tested in community pharmacy sites, these publically available toolkits can
      inform professionals and staff and offer insights for communication improvement. 

PMID- 23867754
TI  - Functional analysis of domain of unknown function (DUF) 1943, DUF1944 and von
      Willebrand factor type D domain (VWD) in vitellogenin2 in zebrafish.
AB  - Vitellogenin (Vg), the precursor of egg-yolk proteins in all oviparous organisms,
      shares a similar domain structure combination. In most cases, Vg contains the
      Vitellogenin_N domain, the domain of unknown function (DUF) 1943, and the von
      Willebrand factor type D domain (VWD), which are present in different forms of Vg
      from both vertebrates and invertebrates. Occasionally, a DUF1944 domain is also
      present in between DUF1943 and VWD in some Vg proteins of vertebrates. Recent
      studies have shown that Vg participates in immune defense of host with multiple
      functions. However, whether all Vg proteins encoded by different vg genes play an
      immune role is unknown. In addition, the correlation of different domains in Vg
      with the multiple immune functions remains completely unclear. Here we
      demonstrated clearly that recombinant proteins, rDUF1943, rDUF1944 and rVWD from
      zebrafish Vg2 interacted with both the Gram-positive bacteria Staphylococcus
      aureus, Bacillus subtilis and Micrococcus luteus and the Gram-negative bacteria
      Escherichia coli and Vibrio anguillarum, as well as their signature components
      LTA and LPS. Moreover, both rDUF1943 and rDUF1944 promoted the phagocytosis of E.
      coli and S. aureus by carp macrophages. These suggest that both DUF1943 and
      DUF1944 as well as VWD may contribute to the function of Vg as a pattern
      recognition receptor, and DUF1943 and DUF1944 also contribute to the function of
      Vg as an opsonin. This study also opens a new angle for identification of
      function of genes of unknown function, which have the domains DUF1943 and
      DUF1944. 

PMID- 23867755
TI  - Involvement of Epac1/Rap1/CaMKI/HDAC5 signaling cascade in the regulation of
      placental cell fusion.
AB  - The placental transcription factor glial cell missing 1 (GCM1) and its target
      gene syncytin-1 are involved in cAMP-stimulated trophoblastic fusion for
      syncytiotrophoblast formation. GCM1 DNA-binding activity is inhibited by
      sumoylation, whereas GCM1 stability is decreased by deacetylation. cAMP enhances
      GCM1 desumoylation through the Epac1/Rap1/CaMKI signaling cascade and CaMKI is
      known to down-regulate class IIa HDAC activity. In this paper, we study whether
      the Epac1/Rap1/CaMKI signaling cascade regulates GCM1 activity and placental cell
      fusion through class IIa HDACs. Interaction and co-localization of GCM1 and HDAC5
      were characterized by co-immunoprecipitation analysis and immunofluorescence
      microscopy (IFM). Regulation of GCM1 transcription activity and syncytin-1
      expression by HDAC5 was studied by transient expression. Phospho-specific
      antibodies against HDAC5, RNA interference and IFM were used to examine the de
      repression of GCM1 activity, syncytin-1 expression and cell-cell fusion by
      Epac1/Rap1/CaMKI signaling cascade in placental BeWo cells expressing
      constitutively active Epac1 and CaMKI. We demonstrate that both GCM1 and HDAC5
      are expressed in the syncytiotrophoblast layer of full-term placenta and the
      nuclei of BeWo cells. The interaction between HDAC5 and GCM1 facilitates GCM1
      deacetylation and suppresses its transcriptional activity. In contrast, Epac1
      stimulates HDAC5 phosphorylation on Ser259 and Ser498 in a Rap1- and CaMKI
      dependent manner leading to nuclear export of HDAC5 and thereby de-repression of
      GCM1 transcriptional activity. Importantly, HDAC5 suppresses syncytin-1
      expression and cell-cell fusion in BeWo cells, which is counteracted by Epac1 and
      CaMKI. Our results reveal a new layer of regulation of GCM1 activity and
      placental cell fusion through the Epac1/Rap1/CaMKI signaling cascade by
      restraining HDAC5 from interacting with and mediating GCM1 deacetylation. 

PMID- 23867756
TI  - snRNAs are reduced in the syncytiotrophoblast: a possible mechanism for
      regulation of human placental protein production.
AB  - The multinucleate syncytiotrophoblast of the human placenta is formed by fusion
      of the underlying cytotrophoblast progenitor cells. The large surface area of the
      syncytiotrophoblast is necessary for transport functions while it also serves as
      the site of synthesis of hormones and steroids. Studies of syncytiotrophoblast
      transcription are puzzling, demonstrating that many of the nuclei in the
      multinucleated syncytium are transcriptionally inactive. To further elucidate RNA
      activity in the syncytiotrophoblast, we investigated expression of snRNAs
      involved in RNA splicing. Using RNA in situ hybridization, we observed that
      snRNAs were markedly reduced in the syncytium throughout the course of pregnancy.
      Recapitulating these results in primary trophoblasts and in trophoblast cell
      lines in vitro, we found, using qRT-PCR and RNA in situ hybridization, that snRNA
      expression is reduced in trophoblasts cultured under fusion conditions. Our
      finding that snRNA is markedly reduced in the syncytiotrophoblast suggests that
      the placenta has evolved a balance between the large surface area essential for
      its transport function and the need to regulate protein production in the
      multinucleated syncytium. 

PMID- 23867757
TI  - Zoledronic acid inhibits human osteoblast activities.
AB  - BACKGROUND: Bisphosphonates are potent inhibitors of bone resorption. These kinds
      of drugs, which are used for the treatment of osteolytic diseases, have been
      associated with the occurrence of oral osteonecrosis, especially in patients over
      60 years old. Current studies have demonstrated that the cytotoxic effects of
      bisphosphonates on osteoblasts play an important role in oral osteonecrosis
      development. OBJECTIVE: The aim of this study was to evaluate the effect of long
      term application of a highly potent bisphosphonate - zoledronic acid (ZA) - on
      human osteoblasts in vitro. METHODS: Human osteoblasts (MG63 cell line) were
      seeded for 72 h in wells of 24-well plates. The Dulbecco's modified Eagle's
      medium (DMEM) was then replaced by culture medium without fetal bovine serum
      (FBS), and the cells were incubated for an additional 24 h, after which ZA was
      added to the DMEM without FBS and incubated in contact with osteoblasts for 7, 14
      or 21 days. Cell viability (CV), total protein production (TPP), alkaline
      phosphatase (ALP) activity, mineral nodule formation (MNF), and gene expression
      of ALP and osteocalcin (OCN), as well as cell morphology by scanning electronic
      microscopy, were evaluated. Data were statistically analyzed by Kruskal-Wallis
      and Mann-Whitney tests, with a significance level of 5%. RESULTS: The cytotoxic
      effects of ZA on osteoblasts were characterized by reduction of CV, TPP, ALP and
      MNF production. In addition, ZA MNF caused a decrease in gene expression of ALP
      and OCN, as well as intense cell morphology alterations. All these negative
      effects of ZA were concentration and period dependent. CONCLUSION: Both
      concentrations of ZA (1 and 5 MUM) caused cytotoxic effects to osteoblasts which
      reduced the production and expression of proteins that play an important role in
      bone matrix synthesis and mineralization.

PMID- 23867758
TI  - Development of Leptospira in vitro potency assays: EU/industry experience and
      perspectives.
AB  - Nobivac(r) Lepto (MSD Animal Health) is a non-adjuvanted canine leptospirosis
      vaccine containing inactivated whole cells of Leptospira interrogans serogroup
      Canicola serovar Portlandvere and L. interrogans serogroup Icterohaemorrhagiae
      serovar Copenhageni. The current standard in vivo potency test is a hamster
      challenge test associated with major drawbacks such as animal suffering and poor
      reproducibility. Here, the quantification of antigenic mass by ELISA as a new in
      vitro potency test is described, supporting the 3Rs concept (replacement,
      reduction, and refinement of animal tests) and in accordance with European
      Pharmacopoeia Monograph 0447 (Canine Leptospirosis Vaccine [Inactivated]). The
      two corresponding sandwich ELISAs are based on monoclonal antibodies specific for
      immunodominant leptospiral lipopolysaccharide epitopes. Protection in passive
      immunization experiments demonstrate that these monoclonal antibodies recognize
      key protective antigens in currently licensed human and veterinary whole cell
      Leptospira vaccines. The high precision and robustness renders the two ELISAs
      much more reliable correlates of potency in dogs than the hamster potency test.
      The recent approval of these assays for a new canine leptospirosis vaccine is an
      important contribution to the 3Rs in quality control testing of Leptospira
      vaccines.

PMID- 23867759
TI  - Incidence and prevalence of inflammatory bowel diseases in gastroenterology
      primary care setting.
AB  - BACKGROUND: The incidence of inflammatory bowel diseases (IBDs) has markedly
      increased over the last years, but no epidemiological study has been performed in
      gastroenterology primary care setting. We describe the epidemiology of IBD in a
      gastroenterology primary care unit using its records as the primary data source.
      METHODS: Case finding used predefined read codes to systematically search
      computer diagnostic and prescribing records from January 2009 to December 2012. A
      specialist diagnosis of Ulcerative colitis (UC), Crohn's disease (CD),
      inflammatory bowel disease unclassified (IBDU) or segmental colitis associated
      with diverticulosis (SCAD), based on clinical, histological or radiological
      findings, was a prerequisite for the inclusion in the study. Secondary, infective
      and apparent acute self-limiting colitis were excluded. RESULTS: We identified
      176 patients with IBD in a population of 94,000 with a prevalence 187.2/100,000
      (95% CI: 160.6-217.0). Between 2009 and 2012 there were 61 new cases. In
      particular, there were 23 new cases of UC, 19 new cases of CD, 15 new cases of
      SCAD, and 4 new cases of IBDU. The incidence of IBD was 16.2/100,000 (95% CI 12.5
      20.7) per year. The incidence per year was 6/100,000 (95% CI 3.8 to 8.9) for UC,
      5/100,000 (95% CI 3.0-7.7) for CD, 4/100,000 (95% CI 2.3-6.5) for SCAD, and
      1/100,000 (95% CI 0.3-2.6) for IBDU. CONCLUSIONS: We assessed for the first time
      which is the prevalence and incidence of IBD in a gastroenterology primary care
      unit. This confirms that specialist primary care unit is a key factor in
      providing early diagnosis of chronic diseases.

PMID- 23867760
TI  - [Advanced uterine prolapse during pregnancy: pre- and postnatal management].
AB  - Pelvic organ prolapse is a common pelvic floor disorder in postmenopausal women.
      The literature is quite poor concerning the management of prolapse during
      pregnancy in young women. We report the case of a 39-year-old multiparous woman
      referred for the treatment of an exteriorized uterine prolapse at 13 weeks of
      gestation. The management of cervical prolapse depends on its stage, its
      evolution and on gestational age. It combines local antiseptics, rest and manual
      reintegration or reduction of the prolapsus using a pessary to prevent ulceration
      of the cervix. In case of stage IV (POP-Q) uterine prolapse, vaginal delivery may
      be compromised. No recommendation is actually available about route of delivery
      in case of exteriorized uterine prolapse. It should be clearly discussed
      regarding the potential risk of cesarean section for dystocia. Surgical repair of
      the prolapse will be discussed after childbirth according to functional
      impairment and women's desire for pregnancy.

PMID- 23867761
TI  - [Proposal of a new methodology: tridimensional colposcopy (3D) of the lower
      genital tract].
AB  - The combination of a colposcope to a computer with a 3D video adapter and a
      dedicated graphics card can get with a specialized 3D visualization deferred
      delayed colposcopic imaging software. The 3-dimensional images allow the
      observation of new aspects of epithelial surfaces from different angles which is
      possible to visualize with this technology alone. 

PMID- 23867762
TI  - Gingivae contain neural-crest- and mesoderm-derived mesenchymal stem cells.
AB  - Gingivae represent a unique soft tissue that serves as a biological barrier to
      cover the oral cavity side of the maxilla and mandible. Recently, the gingivae
      were identified as containing mesenchymal stem cells (GMSCs). However, it is
      unknown whether the GMSCs are derived from cranial neural crest cells (CNCC) or
      the mesoderm. In this study, we show that around 90% of GMSCs are derived from
      CNCC and 10% from the mesoderm. In comparison with mesoderm MSCs (M-GMSCs), CNCC
      derived GMSCs (N-GMSCs) show an elevated capacity to differentiate into neural
      cells and chondrocytes and induce activated T-cell apoptosis in vitro. When
      transplanted into mice with dextran sulfate sodium (DSS)-induced colitis, N-GMSCs
      showed superior effects in ameliorating inflammatory-related disease phenotype in
      comparison with the M-GMSC treatment group. Mechanistically, the increased
      immunomodulatory effect of N-GMSCs is associated with up-regulated expression of
      FAS ligand (FASL), a transmembrane protein that plays an important role in MSC
      based immunomodulation. In summary, our study indicates that the gingivae contain
      both neural-crest- and mesoderm-derived MSCs with distinctive stem cell
      properties.

PMID- 23867763
TI  - The use of feed additives to reduce the effects of aflatoxin and deoxynivalenol
      on pig growth, organ health and immune status during chronic exposure.
AB  - Three feed additives were tested to improve the growth and health of pigs
      chronically challenged with aflatoxin (AF) and deoxynivalenol (DON). Gilts (n =
      225, 8.8 +/- 0.4 kg) were allotted to five treatments: CON (uncontaminated
      control); MT (contaminated with 150 ug/kg AF and 1100 ug/kg DON); A (MT + a clay
      additive); B (MT + a clay and dried yeast additive); and C (MT + a clay and yeast
      culture additive). Average daily gain (ADG) and feed intake (ADFI) were recorded
      for 42 days, blood collected for immune analysis and tissue samples to measure
      damage. Feeding mycotoxins tended to decrease ADG and altered the immune system
      through a tendency to increase monocytes and immunoglobulins. Mycotoxins caused
      tissue damage in the form of liver bile ductule hyperplasia and karyomegaly. The
      additives in diets A and B reduced mycotoxin effects on the immune system and the
      liver and showed some ability to improve growth. The diet C additive played a
      role in reducing liver damage. Collectively, we conclude that AF and DON can be
      harmful to the growth and health of pigs consuming mycotoxins chronically. The
      selected feed additives improved pig health and may play a role in pig growth. 

PMID- 23867764
TI  - Day-night differences in neural activation in histaminergic and serotonergic
      areas with putative projections to the cerebrospinal fluid in a diurnal brain.
AB  - In nocturnal rodents, brain areas that promote wakefulness have a circadian
      pattern of neural activation that mirrors the sleep/wake cycle, with more neural
      activation during the active phase than during the rest phase. To investigate
      whether differences in temporal patterns of neural activity in wake-promoting
      regions contribute to differences in daily patterns of wakefulness between
      nocturnal and diurnal species, we assessed Fos expression patterns in the
      tuberomammillary (TMM), supramammillary (SUM), and raphe nuclei of male grass
      rats maintained in a 12:12 h light-dark cycle. Day-night profiles of Fos
      expression were observed in the ventral and dorsal TMM, in the SUM, and in
      specific subpopulations of the raphe, including serotonergic cells, with higher
      Fos expression during the day than during the night. Next, to explore whether the
      cerebrospinal fluid is an avenue used by the TMM and raphe in the regulation of
      target areas, we injected the retrograde tracer cholera toxin subunit beta (CTB)
      into the ventricular system of male grass rats. While CTB labeling was scarce in
      the TMM and other hypothalamic areas including the suprachiasmatic nucleus, which
      contains the main circadian pacemaker, a dense cluster of CTB-positive neurons
      was evident in the caudal dorsal raphe, and the majority of these neurons
      appeared to be serotonergic. Since these findings are in agreement with reports
      for nocturnal rodents, our results suggest that the evolution of diurnality did
      not involve a change in the overall distribution of neuronal connections between
      systems that support wakefulness and their target areas, but produced a complete
      temporal reversal in the functioning of those systems. 

PMID- 23867765
TI  - Proline-induced changes in acetylcholinesterase activity and gene expression in
      zebrafish brain: reversal by antipsychotic drugs.
AB  - Hyperprolinemia is an inherited disorder of proline metabolism and
      hyperprolinemic patients can present neurological manifestations, such as
      seizures, cognitive dysfunctions, and schizoaffective disorders. However, the
      mechanisms related to these symptoms are still unclear. In the present study, we
      evaluated the in vivo and in vitro effects of proline on acetylcholinesterase
      (AChE) activity and gene expression in the zebrafish brain. For the in vivo
      studies, animals were exposed at two proline concentrations (1.5 and 3.0mM)
      during 1h or 7 days (short- or long-term treatments, respectively). For the in
      vitro assays, different proline concentrations (ranging from 3.0 to 1000 MUM)
      were tested. Long-term proline exposures significantly increased AChE activity
      for both treated groups when compared to the control (34% and 39%). Moreover, the
      proline-induced increase on AChE activity was completely reverted by acute
      administration of antipsychotic drugs (haloperidol and sulpiride), as well as the
      changes induced in ache expression. When assessed in vitro, proline did not
      promote significant changes in AChE activity. Altogether, these data indicate
      that the enzyme responsible for the control of acetylcholine levels might be
      altered after proline exposure in the adult zebrafish. These findings contribute
      for better understanding of the pathophysiology of hyperprolinemia and might
      reinforce the use of the zebrafish as a complementary vertebrate model for
      studying inborn errors of amino acid metabolism.

PMID- 23867766
TI  - Reversal of novelty-induced hyperlocomotion and hippocampal c-Fos expression in
      GluA1 knockout male mice by the mGluR2/3 agonist LY354740.
AB  - Dysfunctional glutamatergic neurotransmission has been implicated in
      schizophrenia and mood disorders. As a putative model for these disorders, a
      mouse line lacking the GluA1 subunit (GluA1-KO) of the alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor displays a robust
      novelty-induced hyperlocomotion associated with excessive neuronal activation in
      the hippocampus. Agonists of metabotropic glutamate 2/3 receptors (mGluR2/3)
      inhibit glutamate release in various brain regions and they have been shown to
      inhibit neuronal activation in the hippocampus. Here, we tested a hypothesis that
      novelty-induced hyperlocomotion in the GluA1-KO mice is mediated via excessive
      hippocampal neuronal activation by analyzing whether an mGluR2/3 agonist inhibits
      this phenotypic feature. GluA1-KO mice and littermate wildtype (WT) controls were
      administered with (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid
      (LY354740) (15 mg/kg, i.p.) 30 min before a 2-h exposure to novel arenas after
      which c-Fos immunopositive cells were analyzed in the hippocampus. LY354740 (15
      mg/kg) decreased hyperactivity in male GluA1-KO mice, with only a minimal effect
      in WT controls. This was observed in two cohorts of animals, one naive to
      handling and injections, another pre-handled and accustomed to injections.
      LY354740 (15 mg/kg) also reduced the excessive c-Fos expression in the dorsal
      hippocampal CA1 pyramidal cell layer in maleGluA1-KO mice, while not affecting c
      Fos levels in WT mice. In female mice, no significant effect for LY354740 (15
      mg/kg) on hyperactive behavior or hippocampal c-Fos was observed in either
      genotype or treatment cohort. A higher dose of LY354740 (30 mg/kg) alleviated
      hyperlocomotion of GluA1-KO males, but not that of GluA1-KO females. In
      conclusion, the excessive behavioral hyperactivity of GluA1-KO mice can be partly
      prevented by reducing neuronal excitability in the hippocampus with the mGluR2/3
      agonist suggesting that the hippocampal reactivity is strongly involved in the
      behavioral phenotype of GluA1-KO mice.

PMID- 23867768
TI  - The effect of Parkinson's disease and levodopa on adaptation of anticipatory
      postural adjustments.
AB  - Postural support alters anticipatory postural adjustments (APAs). Efficient
      adaptation to changes in postural support in reactive and centrally initiated
      postural synergies is impaired in Parkinson's disease (PD). This study examined
      whether APAs are affected differently by familiar and novel supports in people
      with PD, ON and OFF levodopa. The effect of PD and levodopa on the ability to
      immediately adapt APAs to changes in support and refine with practice was also
      investigated. Fourteen people with PD and 14 healthy control participants
      performed 20 single rapid leg lift tasks in four support conditions: unsupported,
      bilateral handgrip (familiar), bite plate (novel) and a combined handgrip+bite
      plate condition. APAs, identified from force plate data, were characterized by an
      increase in the vertical ground reaction force under the lifted leg as a result
      of a shift of weight toward the stance limb. Results showed the ability to
      incorporate familiar and novel external supports into the postural strategy was
      preserved in PD. Controls and PD patients in the OFF state further refined the
      postural strategy with practice as evidenced by changes in amplitude of vertical
      ground reaction forces and forces applied to support apparatus within conditions
      between the initial and final trials. In the ON state, people with PD failed to
      refine the use of postural supports in any condition. The results suggest that
      immediate postural adaptation is intact in people with PD and unaffected by
      levodopa administration but the ability to refine postural adaptations with task
      experience is compromised by dopamine therapy. 

PMID- 23867767
TI  - Immunohistological demonstration of CaV3.2 T-type voltage-gated calcium channel
      expression in soma of dorsal root ganglion neurons and peripheral axons of rat
      and mouse.
AB  - Previous behavioral studies have revealed that CaV3.2 T-type calcium channels
      support peripheral nociceptive transmission and electrophysiological studies have
      established the presence of T-currents in putative nociceptive sensory neurons of
      dorsal root ganglion (DRG). To date, however, the localization pattern of this
      key nociceptive channel in the soma and peripheral axons of these cells has not
      been demonstrated due to lack of isoform-selective anti-CaV3.2 antibodies. In the
      present study a new polyclonal CaV3.2 antibody is used to localize CaV3.2
      expression in rodent DRG neurons using different staining techniques including
      confocal and electron microscopy (EM). Confocal microscopy of both acutely
      dissociated cells and short-term cultures demonstrated strong immunofluorescence
      of anti-CaV3.2 antibody that was largely confined to smaller diameter DRG neurons
      where it co-localized with established immuno-markers of unmyelinated
      nociceptors, such as, CGRP, IB4 and peripherin. In contrast, a smaller proportion
      of these CaV3.2-labeled DRG cells also co-expressed neurofilament 200 (NF200), a
      marker of myelinated sensory neurons. In the rat sciatic nerve preparation,
      confocal microscopy demonstrated anti-CaV3.2 immunofluorescence which was co
      localized with both peripherin and NF200. Further, EM revealed immuno-gold
      labeling of CaV3.2 preferentially in association with unmyelinated sensory fibers
      from mouse sciatic nerve. Finally, we demonstrated the expression of CaV3.2
      channels in peripheral nerve endings of mouse hindpaw skin as shown by co
      localization with Mrgpd-GFP-positive fibers. The CaV3.2 expression within the
      soma and peripheral axons of nociceptive sensory neurons further demonstrates the
      importance of this channel in peripheral pain transmission. 

PMID- 23867769
TI  - The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces
      tremulous jaw movements in rodents: implications for pharmacological models of
      parkinsonian tremor.
AB  - Tetrabenazine (TBZ) is a reversible inhibitor of vesicular monoamine storage that
      is used to treat Huntington's disease. TBZ preferentially depletes striatal
      dopamine (DA), and patients being treated with TBZ often experience parkinsonian
      side effects. The present studies were conducted to investigate the ability of
      TBZ to induce tremulous jaw movements (TJMs), which are a rodent model of
      parkinsonian tremor, and to determine if interference with adenosine A2A receptor
      transmission can attenuate TJMs and other motor effects of TBZ. In rats, TBZ
      (0.25-2.0mg/kg) significantly induced TJMs, which primarily occurred in the 3.0
      7.5-Hz frequency range. The adenosine A2A antagonist MSX-3 (1.25-10.0mg/kg)
      significantly attenuated the TJMs induced by 2.0mg/kg TBZ in rats, and also
      significantly reduced the display of catalepsy and locomotor suppression induced
      by TBZ. In mice, TBZ (2.5-10.0mg/kg) dose dependently induced TJMs, and adenosine
      A2A receptor knockout mice showed significantly fewer TJMs compared to wild-type
      controls. MSX-3 (2.5-10.0mg/kg) also significantly reduced TBZ-induced TJMs in
      CD1 mice. To provide a cellular marker of these pharmacological conditions, we
      examined c-Fos expression in the ventrolateral neostriatum (VLS). TBZ (2.0mg/kg)
      significantly increased the number of c-Fos-positive cells in the VLS, which is
      indicative of reduced DA D2 receptor transmission, and 10.0mg/kg MSX-3
      significantly attenuated the TBZ-induced c-Fos expression. These results indicate
      that TBZ induces tremor as measured by the TJM model, and that pharmacological
      antagonism and genetic deletion of adenosine A2A receptors are capable of
      attenuating this oral tremor. 

PMID- 23867770
TI  - Scratching inhibits serotonin-evoked responses of rat dorsal horn neurons in a
      site- and state-dependent manner.
AB  - Scratching inhibits pruritogen-evoked responses of neurons in the superficial
      dorsal horn, implicating a spinal site for scratch inhibition of itch. We
      investigated if scratching differentially affects neurons depending on whether
      they are activated by itchy vs. painful stimuli, and if the degree of inhibition
      depends on the relative location of scratching. We recorded from rat lumbar
      dorsal horn neurons responsive to intradermal (id) microinjection of serotonin (5
      hydroxytryptamine, 5-HT). During the response to 5-HT, scratch stimuli (3mm, 300
      mN, 2 Hz, 20s) were delivered at the injection site within the mechanosensitive
      receptive field (on-site), or 4-30 mm away, outside of the receptive field (off
      site). During off-site scratching, 5-HT-evoked firing was significantly
      attenuated followed by recovery. On-site scratching excited neurons, followed by
      a significant post-scratch decrease in 5-HT-evoked firing. Most neurons
      additionally responded to mustard oil (allyl isothiocyanate). Off-site scratching
      had no effect, while on-site scratching excited the neurons. These results
      indicate that scratching exerts a state-dependent inhibitory effect on responses
      of spinal neurons to pruritic but not algesic stimuli. Moreover, on-site
      scratching first excited neurons followed by inhibition, while off-site
      scratching immediately evoked the inhibition of pruritogen-evoked activity. This
      accounts for the suppression of itch by scratching at a distance from the site of
      the itchy stimulus.

PMID- 23867771
TI  - Molecular links between Alzheimer's disease and diabetes mellitus.
AB  - Substantial epidemiological evidence shows an increased risk for developing
      Alzheimer's disease (AD) in people with diabetes. Yet the underlying molecular
      mechanisms still remain to be elucidated. This article reviews the current
      studies on common pathological processes of Alzheimer's disease and diabetes with
      particular focus on potential mechanisms through which diabetes affects the
      initiation and progression of Alzheimer's disease. Impairment of insulin
      signaling, inflammation, oxidative stress, mitochondrial dysfunction, advanced
      glycation end products, APOEepsilon4 and cholesterol appear to be important
      mediators and are likely to act synergistically in promoting AD pathology.

PMID- 23867773
TI  - Influence of the scaffolding protein Zonula Occludens (ZOs) on membrane channels.
AB  - Zonula Occludens (ZO) proteins are ubiquitous scaffolding proteins providing the
      structural basis for the assembly of multiprotein complexes at the cytoplasmic
      surface of the plasma membrane and linking transmembrane proteins to the
      filamentous cytoskeleton. They belong to the large family of membrane-associated
      guanylate kinase (MAGUK)-like proteins comprising a number of subfamilies based
      on domain content and sequence similarity. ZO proteins were originally described
      to localize specifically to tight junctions, or Zonulae Occludentes, but this
      notion was rapidly reconsidered since ZO proteins were found to associate with
      adherens junctions as well as with gap junctions, particularly with connexin-made
      intercellular channels, and also with a few other membrane channels. Accumulating
      evidence reveals that in addition to having passive scaffolding functions in
      organizing gap junction complexes, including connexins and cytoskeletals, ZO
      proteins (particularly ZO-1) also actively take part in the dynamic function as
      well as in the remodeling of junctional complexes in a number of cellular
      systems. This article is part of a Special Issue entitled: Reciprocal influences
      between cell cytoskeleton and membrane channels, receptors and transporters.
      Guest Editor: Jean Claude Herve. 

PMID- 23867774
TI  - Compositional and structural characterization of monolayers and bilayers composed
      of native pulmonary surfactant from wild type mice.
AB  - This work comprises a structural and dynamical study of monolayers and bilayers
      composed of native pulmonary surfactant from mice. Spatially resolved information
      was obtained using fluorescence (confocal, wide field and two photon excitation)
      and atomic force microscopy methods. Lipid mass spectrometry experiments were
      also performed in order to obtain relevant information on the lipid composition
      of this material. Bilayers composed of mice pulmonary surfactant showed
      coexistence of distinct domains at room temperature, with morphologies and
      lateral packing resembling the coexistence of liquid ordered (lo)/liquid
      disordered (ld)-like phases reported previously in porcine lung surfactant.
      Interestingly, the molar ratio of saturated (mostly DPPC)/non-saturated
      phospholipid species and cholesterol measured in the innate material corresponds
      with that of a DOPC/DPPC/cholesterol mixture showing lo/ld phase coexistence at a
      similar temperature. This suggests that at quasi-equilibrium conditions, key
      lipid classes in this complex biological material are still able to produce the
      same scaffold observed in relevant but simpler model lipid mixtures. Also, robust
      structural and dynamical similarities between mono- and bi-layers composed of
      mice pulmonary surfactant were observed when the monolayers reach a surface
      pressure of 30mN/m. This value is in line with theoretically predicted and
      recently measured surface pressures, where the monolayer-bilayer equivalence
      occurs in samples composed of single phospholipids. Finally, squeezed out
      material attached to pulmonary surfactant monolayers was observed at surface
      pressures near the beginning of the monolayer reversible exclusion plateau
      (~40mN/m). Under these conditions this material adopts elongated tubular shapes
      and displays ordered lateral packing as indicated by spatially resolved LAURDAN
      GP measurements. 

PMID- 23867775
TI  - Anaesthesia for renal transplant surgery.

PMID- 23867776
TI  - Validation of rotational thromboelastometry during cardiopulmonary bypass: A
      prospective, observational in-vivo study.
AB  - BACKGROUND: Rotational thromboelastometry (ROTEM) is a whole blood point-of-test
      used to assess the patient's coagulation status. Three of the available ROTEM
      tests are EXTEM, INTEM and HEPTEM. In the latter, heparinase added to the INTEM
      reagent inactivates heparin to reveal residual heparin effect. Performing ROTEM
      analysis during cardiopulmonary bypass (CPB) might allow the anaesthesiologist to
      anticipate the need for blood products. OBJECTIVE: The goal of this study was to
      validate ROTEM analysis in the presence of very high heparin concentrations
      during CPB. DESIGN: Prospective, observational trial. SETTING: Single University
      Hospital. PARTICIPANTS: Twenty patients undergoing coronary artery bypass
      grafting. MAIN OUTCOME MEASURE: ROTEM analysis was performed before heparin
      administration (T0), 10 min after heparin (T1), at the end of CPB (T2) and 10 min
      after protamine (T3). The following tests were performed: EXTEM, INTEM, and
      HEPTEM. Heparin concentrations were measured at T1 and at the end of bypass (T2).
      RESULTS: At T1, EXTEM differed from baseline for coagulation time: +26.7 s (18.4
      to 34.9, P < 0.0001), alpha: -3 degrees  (1.0 to 5.4, P = 0.006) and A10: -4.4 mm
      (2.3 to 6.5, P = 0.0004). INTEM at T0 was different from HEPTEM at T1 for
      coagulation time: + 47 s (34.3 to 59.6, P > 0.0001), A10: -2.3 mm (0.5 to 4.0, P
      = 0.01) and alpha -2 degrees  (1.0 to 3.0; P = 0.0007). At T2, all parameters in
      EXTEM and HEPTEM related to fibrin-platelet interaction deteriorated
      significantly compared to T1. At T3, EXTEM and INTEM were comparable to EXTEM and
      HEPTEM at T2. CONCLUSION: HEPTEM and EXTEM measurements are valid in the presence
      of very high heparin concentrations and can be performed before protamine
      administration in patients undergoing cardiac surgery with CPB. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT01455454.

PMID- 23867777
TI  - Influence of neuromuscular block and reversal on bispectral index and NeuroSense
      values.

PMID- 23867778
TI  - Reply to: Etomidate for critically ill patients: still a matter for pro-con
      debates?

PMID- 23867779
TI  - Reply to: Anaesthesia for renal transplant surgery.

PMID- 23867780
TI  - The base excess gap is not a valid tool for the quantification of unmeasured ions
      in cardiac surgical patients: a retrospective observational study.
AB  - BACKGROUND: The base excess gap (BE(gap)) method is commonly used for the
      quantification of unmeasured ions in critically ill patients. However, it has
      never been validated against the standard quantitative acid-base approach.
      OBJECTIVE: To compare the BE(gap) as a tool for the prediction of the excess of
      unmeasured ions with the offset of strong ion gap (SIG) from its reference value.
      DESIGN: A retrospective observational study. SETTING: Adult ICU in a tertiary
      hospital. PATIENTS: One hundred and thirty-five cardiac surgical patients
      admitted for postoperative care. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      BE(gap) was calculated as BE(gap) = SBE - BE(si) - BE(wa), where SBE is the
      standard base excess, BE(si) is the partition due to strong ions ([Na+]-[Cl-]
      [lactate-] - 30.5) and BE(wa) is the partition due to weak acids [0.25*{42 -
      (albumin)}]. The deviation of the observed SIG (SIG(ob)) from its reference value
      was calculated as deltaSIG = 2.85 - SIG(ob). We used Bland-Altman and concordance
      correlation analysis to compare BE(gap) with deltaSIG. A bias of +/-1 meq l(-1)
      with limits of agreement of +/-2 meq l(-1) and a concordant correlation
      coefficient of more than 0.9 were considered to indicate a strong agreement.
      RESULTS: The concordant correlation coefficient between BE(gap) and deltaSIG was
      0.702. The mean bias between the two variables was 1.8 meq l(-1), with a lower
      limit of agreement of -0.9 meq l(-1) and an upper limit of agreement of 4.4 meq
      l(-1). CONCLUSION: The BE gap method cannot reliably quantify the unmeasured ion
      excess in cardiac surgical patients. Clinicians should use the full Stewart-Figge
      model for quantitative acid-base assessments.

PMID- 23867781
TI  - Effects of dietary supplementation of coriander oil, in canola oil diets, on the
      metabolism of [1-(14)C] 18:3n-3 and [1-(14)C] 18:2n-6 in rainbow trout
      hepatocytes.
AB  - The aim of this study was to investigate the effects of petroselinic acid, found
      in coriander oil, on the ability of rainbow trout hepatocytes to increase the
      production of eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid
      (22:6n-3; DHA) from [1-(14)C] alpha-linolenic acid (18:3n-3; ALA) and to reduce
      the production of arachidonic acid (20:4n-6; ARA) from [1-(14)C] 18:2n-6.
      Addition of coriander oil increased the production of 22:6n-3, from [1-(14)C]
      18:3n-3, at the 0.5 and 1.0% inclusion levels and reduced the conversion of [1
      (14)C] 18:2n-6 to 20:4n-6. beta-Oxidation was significantly increased at the 1.5%
      inclusion level for [1-(14)C] 18:2n-6, however beta-oxidation for [1-(14)C] 18:3n
      3 only showed an increasing trend. Acetate, a main breakdown product of fatty
      acids (FA) via peroxisomal beta-oxidation, decreased three-fold for [1-(14)C]
      18:2n-6 and nearly doubled for [1-(14)C] 18:3n-3 when coriander was added at a
      1.5% inclusion level. Acyl coenzyme A oxidase (ACO) enzyme activity showed no
      significant differences between treatments. Relative gene expression of ?6
      desaturase decreased with addition of coriander oil compared to the control. The
      addition of petroselinic acid via coriander oil to vegetable oil (VO) based diets
      containing no fishmeal (FM) or fish oil (FO), significantly increased the
      production of anti-inflammatory precursor 22:6n-3 (P=0.011) and decreased pro
      inflammatory precursor 20:4n-6 (P=0.023) in radiolabelled hepatocytes of rainbow
      trout. 

PMID- 23867772
TI  - Differential striatal spine pathology in Parkinson's disease and cocaine
      addiction: a key role of dopamine?
AB  - In the striatum, the dendritic tree of the two main populations of projection
      neurons, called "medium spiny neurons (MSNs)", are covered with spines that
      receive glutamatergic inputs from the cerebral cortex and thalamus. In
      Parkinson's disease (PD), striatal MSNs undergo an important loss of dendritic
      spines, whereas aberrant overgrowth of striatal spines occurs following chronic
      cocaine exposure. This review examines the possibility that opposite dopamine
      dysregulation is one of the key factors that underlies these structural changes.
      In PD, nigrostriatal dopamine degeneration results in a significant loss of
      dendritic spines in the dorsal striatum, while rodents chronically exposed to
      cocaine and other psychostimulants, display an increase in the density of "thin
      and immature" spines in the nucleus accumbens (NAc). In rodent models of PD,
      there is evidence that D2 dopamine receptor-containing MSNs are preferentially
      affected, while D1-positive cells are the main targets of increased spine density
      in models of addiction. However, such specificity remains to be established in
      primates. Although the link between the extent of striatal spine changes and the
      behavioral deficits associated with these disorders remains controversial, there
      is unequivocal evidence that glutamatergic synaptic transmission is significantly
      altered in both diseased conditions. Recent studies have suggested that opposite
      calcium-mediated regulation of the transcription factor myocyte enhancer factor 2
      (MEF2) function induces these structural defects. In conclusion, there is strong
      evidence that dopamine is a major, but not the sole, regulator of striatal spine
      pathology in PD and addiction to psychostimulants. Further studies of the role of
      glutamate and other genes associated with spine plasticity in mediating these
      effects are warranted. 

PMID- 23867782
TI  - Using doubly labeled water to validate associations between sugar-sweetened
      beverage intake and body mass among White and African-American adults.
AB  - BACKGROUND: Evidence is mixed regarding sugar-sweetened beverage (SSB) intake and
      adiposity among adults, perhaps because of reporting bias. OBJECTIVE: The
      objective of this study is to determine the impact of reporting bias on any
      associations between increased SSB intake and overweight/obesity. DESIGN:
      Beverage intake and overweight/obese status (body mass index >= 25 kg m(-2)) were
      examined among adults from a dietary assessment and doubly labeled water study
      (n=250). Four web-based, 24-h recalls assessed dietary intake. SSB intake was
      categorized as no intake, 1-99 kcals per day and >99 kcals per day. Logistic
      regression models adjusted for total caloric intake, age, race, education and
      diet quality compared SSB intake with overweight/obese status. To investigate
      dietary self-reporting bias, analyses were replicated in a subset of 'true
      reporters': those with self-reported total caloric intake within 25% of total
      energy expenditure per doubly labeled water assessments (n=108). RESULTS: One
      half of participants were overweight/obese; more overweight/obese participants
      consumed SSB than normal-weight participants (69% vs 47%; P<0.001). Intake of
      other beverages did not differ by adiposity. Less number of White participants
      (48%) consumed SSB compared with African-American participants (68%; P=0.002).
      Compared with no intake, SSB intake up to the median intake doubled the risk of
      being overweight/obese (odds ratio: 2.1, 95% confidence interval: 1.0-4.3;
      P=0.046) and SSB intake over the median more than doubled the risk (odds ratio:
      2.6, 95% confidence interval: 1.2-6.0; P=0.018). When limited to true reporters,
      SSB intake significantly increased the risk of being overweight/obese by nearly
      fourfold. CONCLUSION: Underreporting of SSB intake may be attenuating true
      associations of SSB intake and the risk of being overweight/obese.

PMID- 23867783
TI  - Functional outcomes following catheter-based iliac vein stent placement.
AB  - OBJECTIVES: Although previous reports have demonstrated the efficacy of catheter
      directed thrombolytic therapy and iliac vein stent placement for the management
      of iliofemoral deep vein thrombosis (DVT), functional outcomes remain undefined.
      The purpose of this study was to determine midterm outcomes and functional
      quality of life among patients treated with iliac vein stenting. METHODS: Records
      of all the patients treated with iliac vein stent placement between March 2004
      and March 2011 were examined for primary patency, assisted primary patency, and
      secondary patency. Midterm functional outcomes were measured quantitatively,
      including ongoing symptoms and return to work status. RESULTS: Over the study
      interval, 32 patients (33 limbs) underwent iliac vein stent placement. In all,
      72% (n = 23) of these patients were female, with an average age of 43 years. In
      all, 78% (n = 25) of the patients were diagnosed with acute DVT, 89% of which
      occurred in the left leg. Catheter-directed thrombolysis was utilized in 92% (23
      of 25) of the patients with acute DVT. All patients treated with thrombolysis and
      stent placement presented with pain and edema in the affected limb. One-year
      primary, assisted primary, and secondary patencies were 75%, 96%, and 96%,
      respectively. Freedom from reintervention at 1 year was 83%. Treatment was
      associated with a sustained significant reduction in pain (91% vs 6%, P < .001)
      and edema (97% vs 12%, P < .001) at a mean follow-up of 29 months (range 5-83
      months), at which time 89% of the patients reported to be at their pre-DVT
      functional status. CONCLUSIONS: Aggressive therapy of symptomatic iliac vein
      stenosis or occlusion with venography, catheter-directed thrombolysis, and iliac
      vein stent placement provides durable patency and freedom from reintervention.
      Most patients can anticipate good functional recovery with decreased pain,
      decreased edema, and high likelihood of returning to work.

PMID- 23867784
TI  - Carotid cavernous fistulae occurring after the use of the Fogarty catheter in
      carotid surgery: a review.
AB  - The Fogarty catheter represents a major advancement for the effective removal of
      distal thrombi during vascular surgery, including carotid endarterectomy (CEA).
      One complication related to its use is injury to the cavernous carotid artery
      with development of a carotid cavernous fistula (CCF). Including a recent case at
      our institution, 21 patients with a Fogarty-related CCF have been reported since
      1967. We performed a detailed review of all Fogarty-related CCFs during the
      treatment of carotid occlusive disease. We suggest a management algorithm for
      post-CEA acute carotid occlusion. 

PMID- 23867785
TI  - Management of a patient with Turner syndrome presenting with an isolated left
      subclavian artery aneurysm.
AB  - We describe a case of a 52-year-old female with Turner syndrome found to have an
      isolated 3.5-cm left subclavian artery aneurysm. Surgical intervention was
      performed to decrease the risk of compressive symptoms, distal embolization, and
      rupture. This entailed exclusion of the aneurysm proximally using thoracic stent
      graft, carotid-subclavian bypass, and ligation of the subclavian artery distal to
      the aneurysm. One-year follow-up demonstrated exclusion of the aneurysm with a 5
      mm reduction in maximum aneurysm sac diameter. This case represents the
      management of a rare isolated left subclavian artery aneurysm, in the setting of
      Turner syndrome, treated with a successful endovascular approach. 

PMID- 23867786
TI  - Facing death in clinical practice: a view from physicians in Mexico.
AB  - OBJECTIVE: Physicians' decisions and actions, once they know that their patients'
      death is inevitable, will influence how patients are going to live their last
      moments. The purpose of the present study was to explore the views of physicians
      about death in their clinical practices. METHODS: Physicians who work at four
      high-specialty public hospitals and two private hospitals in Mexico City provided
      responses to the Physicians' Views about Death Questionnaire, which was developed
      for this study. RESULTS: Four hundred thirteen physicians were surveyed. The
      majority treat terminally ill patients (73.3%), but only 28% received training
      regarding death. Nearly half of the physicians reported a personal formative
      experience related to death which, together with the experience of being exposed
      to terminally ill patients, appear to be the manner in which the majority of
      physicians learn to deal with death. The great majority of participants (90.6%)
      would personally like to know the truth if they were going to die. Younger
      physicians, those with <6 years of medical practice, those with no death-related
      personal formative experience, no death-related academic training, and no
      experience treating terminally ill patients were most likely to avoid telling
      patients about their imminent death. CONCLUSIONS: Death is an important topic for
      physicians in Mexico. There is a relation between lack of information,
      experience, and formal training, and the withholding of information from dying
      patients. This suggests a possible value for interventions to enhance and develop
      coping skills for professionals who deal with end-of-life situations.

PMID- 23867787
TI  - Rutin exerts antitumor effects on nude mice bearing SW480 tumor.
AB  - BACKGROUND AND AIMS: We previously showed that extracts from Phoradendron
      serotinum and Croton lechleri exerted in vitro cytotoxic and in vivo antitumor
      effects and that their main component was rutin (RTN; 3-rhamnosyl
      glucosylquercetin). However, it is unknown whether RTN exerts in vivo antitumoral
      effects on human colon cancer cells. The aim of this work was to evaluate the
      antitumor effects of RTN on a murine model. METHODS: Cytotoxic effects of RTN on
      human cancer and non-tumorigenic cell lines were evaluated using the MTT assay.
      Different doses of RTN were injected intraperitoneally daily into nu/nu mice
      bearing tumors of SW480 colon cancer cells during 32 days. The growth and weight
      of tumors were measured. Serum levels of VEGF, survival time, increase in life
      span and toxicological effects on body weight and organ weight were also
      analyzed. RESULTS: RTN showed the highest cytotoxic effects against SW480 cells
      (IC50 = 125 MUM) as compared to the other cancer cells lines and decreased, in a
      dose dependent manner, the tumor volume and weight of mice bearing SW480 tumor.
      RTN 20 mg/kg, the highest dose tested, lacked toxic effects on body weight and
      relative organ weight in mice, increased mean survival time by 50 days, and
      decreased by 55% the VEGF serum levels compared to untreated mice. CONCLUSIONS:
      RTN exerts in vitro cytotoxic effects on SW480 cells, induces in vivo antitumor
      effects, lacks toxic effects on mice bearing SW480 tumor and exerts
      antiangiogenic properties.

PMID- 23867788
TI  - Polio eradication: how long and how much to the end?
AB  - Eradication of poliomyelitis seems to be more feasible than ever. During recent
      years the strategy has reached milestone goals, faced new challenges, and re
      configured by itself. In this text we describe the current situation of the polio
      eradication efforts worldwide and present an analysis of the potential
      implications and needs regarding vaccination in the coming years. 

PMID- 23867789
TI  - Effect of jujube honey on Candida albicans growth and biofilm formation.
AB  - BACKGROUND AND AIMS: Candida species, especially Candida albicans, are major
      fungal pathogens of humans that are capable of causing superficial mucosal
      infections and systemic infections in humans. The aim of this study was to
      evaluate the jujube (Zizyphus spina-christi) honey for its in vitro inhibitory
      activity against pre-formed biofilm and its interference with the biofilm
      formation of C. albicans. METHODS: The XTT reduction assay, scanning electron
      microscopy (SEM) and atomic force microscopy (AFM) were employed to determine the
      inhibitory effect of Jujube honey on C. albicans biofilm. Changes in the infrared
      spectrum after treatment with honey were also determined by Fourier transform
      infrared (FTIR) spectroscopy. RESULTS: Jujube honey affects biofilms by
      decreasing the size of mature biofilms and by disruption of their structure. At a
      concentration of 40% w/v, it interferes with formation of C. albicans biofilms
      and disrupts established biofilms. The SEM and AFM results indicated that this
      type of honey affected the cellular morphology of C. albicans and decreased
      biofilm thickness. CONCLUSIONS: The present findings show that jujube honey has
      antifungal properties against C. albicans and has the ability to inhibit the
      formation of C. albicans biofilms and disrupt established biofilms.

PMID- 23867791
TI  - Risedronate positively affects osteogenic differentiation of human mesenchymal
      stromal cells.
AB  - BACKGROUND AND AIMS: Bisphosphonates are widely used for the treatment of bone
      pathologies, mainly due to their ability to inhibit osteoclastic activity and
      thus bone resorption. Yet, their potential effect on bone formation is unclear.
      Our aim was to determine whether risedronate can affect osteoblastic
      differentiation of mesenchymal stromal cells (MSC). METHODS: We evaluated the
      effect of the risedronate, which is a bisphosphonate widely used in clinical
      settings, on the differentiation of precursor cells of osteoblasts and
      adipocytes. Thus, MSC from human bone marrow were induced to differentiate into
      osteoblasts or adipocytes in the presence or absence of two risedronate
      concentrations (10-8 M and 10-9 M). RESULTS: Risedronate increased the levels of
      osteogenic markers including the extracellular matrix mineralization on cells
      induced to osteoblasts. On the other hand, such bisphosphonates did not have
      significant effects on the ppargamma2 and lpl adipogenic genes or the fat vesicle
      accumulation on the cells induced into adipocytes. In addition, it increased the
      expression of early osteogenic differentiation genes like runx2 on MSC not
      induced to differentiate. CONCLUSIONS: Risedronate concentrations used favor the
      osteogenic differentiation and the MSC commitment towards osteoblasts. This
      suggests the possibility of using this bisphosphonate in cyclic bone treatments
      with anabolic drugs, enhancing the effect of the latter via a previous MSC
      commitment to preosteoblasts.

PMID- 23867790
TI  - In vitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic
      disease: a pilot study.
AB  - BACKGROUND AND AIMS: We tested the effects of recombinant insulin-like growth
      factor-I (IGF-I) in an adipocyte model of HIV lipodystrophy and in an open label
      study on body composition and metabolism in patients with HIV lipodystrophy.
      METHODS: The effects of IGF-I on ritonavir-induced adipocyte cell death were
      studied in vitro. We assessed lipid accumulation, IGF signaling, apoptosis, and
      gene expression. We conducted a 24-week open label trial of recombinant IGF-I in
      ten adults with HIV associated lipoatrophy. Laboratory assessments included
      glucose, insulin, lipids, and IGF-I. At weeks 0 and 24, body composition studies
      were performed including skinfold measurement, dual-energy x-ray absorptiometry,
      and computed tomography of the abdomen and thigh. RESULTS: In vitro, ritonavir
      increased delipidation and apoptosis of adipocytes, whereas co-treatment with IGF
      I attenuated the effect. In the clinical study, subcutaneous adipose tissue did
      not increase in patients after treatment with IGF-I; however, there was a
      decrease in the proportion of abdominal fat (39.8 +/- 7% vs. 34.6 +/- 7%, p =
      0.007). IGF-I levels increased with treatment (143 +/- 28 MUg/L at week 0 vs. 453
      +/- 212 MUg/L at week 24, p = 0.002), whereas IGFBP-3 levels declined (3.554 +/-
      1.146 mg/L vs. 3.235 +/- 1.151 mg/L, p = 0.02). Insulin at week 12 decreased
      significantly (90.1 +/- 39.8 pmol/L vs. 33.2 +/- 19.6 pmol/L, p = 0.002). There
      was a nonsignificant decrease in visceral adipose tissue (155.2 +/- 68 cm2 at
      week 0 vs. 140.6 +/- 70 cm2 at week 24, p = 0.08). CONCLUSIONS: Use of
      recombinant IGF-I may lower fasting insulin and abdominal fat in patients with
      lipoatrophy associated with HIV infection. Further evaluation of this agent for
      treatment of HIV-associated lipodystrophy may be warranted.

PMID- 23867792
TI  - Dynamic topographical pattern classification of multichannel prefrontal NIRS
      signals.
AB  - OBJECTIVE: Near-infrared spectroscopy (NIRS) is an optical imaging technique that
      has recently been considered for brain-computer interface (BCI) applications. To
      date, NIRS-BCI studies have primarily made use of temporal features of brain
      activity, derived from the time-course of optical signals measured from discrete
      locations, to differentiate mental states. However, functional brain imaging
      studies have indicated that the spatial distribution of haemodynamic activity is
      also rich in information. Thus, the progression of a response over both time and
      space may be valuable to brain state classification. In this paper, we
      investigate the implication of including spatiotemporal features in the single
      trial classification of haemodynamic events for a two-class problem by exploiting
      this information from dynamic NIR topograms. APPROACH: The value of
      spatiotemporal information was explored through a comparative analysis of four
      different classification schemes performed on multichannel NIRS data collected
      from the prefrontal cortex during a mental arithmetic activation task and rest.
      Employing a linear discriminant classifier, data were analysed using
      spatiotemporal features, temporal features, and a collective pool of
      spatiotemporal and temporal features. We also considered a majority vote
      combination of three classifiers; each established using one of the above feature
      sets. Lastly, two separate task durations (20 and 10 s) were considered for
      feature extraction. MAIN RESULTS: With features from the longer task interval,
      the highest overall classification accuracy was achieved using the majority
      voting classifier (76.1 +/- 8.4%), which was greater than the accuracy obtained
      using temporal features alone (73.5 +/- 8.5%) (F3,144 = 7.04, p = 0.0002). While
      results from the shorter task duration were lower overall, the classifier
      employing only spatiotemporal features (with an average accuracy of 67.9 +/-
      9.3%) achieved a higher average accuracy than the rate obtained using only
      temporal features (64.4 +/- 8.4%) (F3,144 = 18.58, p < 10(-4)). SIGNIFICANCE:
      Collectively, these results suggest that spatiotemporal information can be of
      value in the analysis of functional NIRS data, and improved classification rates
      may be obtained in future NIRS-BCI applications with the inclusion of this
      information.

PMID- 23867793
TI  - The TaqI gene polymorphisms of VDR and the circulating 1,25-dihydroxyvitamin D
      levels confer the risk for the keloid scarring in Chinese cohorts.
AB  - AIM: to investigate the association between vitamin D receptor polymorphisms and
      circulating 1,25-Dihydroxyvitamin D (1,25(OH)2D) levels with keloid scar (KS)
      risk. METHODS: A total of 261 patients with KS and 261 normal healthy individuals
      were enrolled. VDR gene polymorphisms were determined. Circulating 1,25(OH)2D
      levels were detected. RESULTS: In this study, we investigated the role of four
      loci of VDR gene polymorphisms in determining the risk of KS in a Chinese cohort.
      We found that the TaqI C>T polymorphism was closely associated with the KS
      incidence. Carriers with CC genotype of TaqI had a higher chance of developing
      KS. Stratification analyses by sex showed that this trend exists only in female
      subjects but not in male subjects. Furthermore, the TaqI C>T polymorphism affects
      the circulating 25-Hydroxyvitamin D levels. The CC carriers had a significantly
      lower mean circulating 1,25(OH)2D level than TT carriers and CT carriers. KS
      subjects had significantly lower mean serum circulating 1,25(OH)2D level than
      controls. The receiver operating characteristic curve analysis revealed that the
      serum circulating 1,25(OH)2D level at the cut-off point of 16.1 ng/ml could
      discriminate KS subjects from controls. CONCLUSION: Collectively, these data
      provide evidence that the vitamin D/VDR pathway plays an important role in the
      development of KS. The TaqI gene polymorphisms of VDR and circulating 1,25(OH)2D
      levels may thus be used as potential markers for prediction of KS development.

PMID- 23867794
TI  - Infantile exposure to lead and late-age cognitive decline: relevance to AD.
AB  - BACKGROUND: Early-life lead (Pb) exposure induces overexpression of the amyloid
      beta precursor protein and its amyloid beta product in older rats and primates.
      We exposed rodents to Pb during different life span periods and examined
      cognitive function in old age and its impact on biomarkers associated with
      Alzheimer's disease (AD). METHODS: Morris, Y, and the elevated plus mazes were
      used. Western blot, quantitative polymerase chain reaction (qPCR), and enzyme
      linked immunosorbent assay were used to study the levels of AD biomarkers.
      RESULTS: Cognitive impairment was observed in mice exposed as infants but not as
      adults. Overexpression of AD-related genes (amyloid beta precursor protein and
      beta-site amyloid precursor protein cleaving enzyme 1) and their products, as
      well as their transcriptional regulator-specificity protein 1 (Sp1)-occurred only
      in older mice with developmental exposure to Pb. CONCLUSIONS: A window of
      vulnerability to Pb neurotoxicity exists in the developing brain that can
      influence AD pathogenesis and cognitive decline in old age.

PMID- 23867795
TI  - Gray matter atrophy pattern in elderly with subjective memory impairment.
AB  - BACKGROUND: Individuals with subjective memory impairment (SMI) report worsening
      of memory without impairment in cognitive tests. Despite normal cognitive
      performance, they may be at higher risk of cognitive decline compared with
      individuals without SMI. METHODS: We used a discriminative function (a support
      vector machine) trained on an independent data set of 226 healthy control
      subjects and 191 patients with probable Alzheimer's disease (AD) dementia to
      characterize the baseline gray matter patterns of 24 individuals with SMI and 53
      control subjects. We tested for associations of these gray matter patterns with
      SMI presence, cognitive performance at baseline, and cognitive decline at follow
      up. RESULTS: Individuals with SMI showed greater similarity to an AD gray matter
      pattern compared with control subjects without SMI. In addition, episodic memory
      decline was associated with an AD gray matter pattern in the SMI group.
      CONCLUSIONS: Our results indicate a link between the gray matter atrophy pattern
      of patients with AD and the presence of SMI. Furthermore, multivariate pattern
      recognition approaches seem to be a sensitive method for identifying subtle brain
      changes that correspond to future memory decline in SMI.

PMID- 23867796
TI  - Osteoprotegerin contributes to the metastatic potential of cells with a
      dysfunctional TSC2 tumor-suppressor gene.
AB  - In addition to its effects on bone metabolism, osteoprotegerin (OPG), a soluble
      member of the tumor necrosis factor family of receptors, promotes smooth muscle
      cell proliferation and migration and may act as a survival factor for tumor
      cells. We hypothesized that these cellular mechanisms of OPG may be involved in
      the growth and proliferation of lymphangioleiomyomatosis (LAM) cells, abnormal
      smooth muscle-like cells with mutations in one of the tuberous sclerosis complex
      tumor-suppressor genes (TSC1/TSC2) that cause LAM, a multisystem disease
      characterized by cystic lung destruction, lymphatic infiltration, and abdominal
      tumors. Herein, we show that OPG stimulated proliferation of cells cultured from
      explanted LAM lungs, and selectively induced migration of LAM cells identified by
      the loss of heterozygosity for TSC2. Consistent with these observations, cells
      with TSC2 loss of heterozygosity expressed the OPG receptors, receptor activator
      of NF-kappaB ligand, syndecan-1, and syndecan-2. LAM lung nodules showed
      reactivities to antibodies to tumor necrosis factor-related apoptosis-inducing
      ligand, receptor activator of NF-kappaB ligand, syndecan-1, and syndecan-2. LAM
      lung nodules also produced OPG, as shown by expression of OPG mRNA and
      colocalization of reactivities to anti-OPG and anti-gp100 (HMB45) antibodies in
      LAM lung nodules. Serum OPG was significantly higher in LAM patients than in
      normal volunteers. Based on these data, it appears that OPG may have tumor
      promoting roles in the pathogenesis of lymphangioleiomyomatosis, perhaps acting
      as both autocrine and paracrine factors. 

PMID- 23867797
TI  - Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA
      desaturases 1 and 2.
AB  - Type 2 diabetes mellitus is characterized by dyslipidemia with elevated free
      fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and
      podocytes are highly susceptible to saturated FFAs but not to protective,
      monounsaturated FFAs. We report that patients with diabetic nephropathy develop
      alterations in glomerular gene expression of enzymes involved in fatty acid
      metabolism, including induction of stearoyl-CoA desaturase (SCD)-1, which
      converts saturated to monounsaturated FFAs. By IHC of human renal biopsy
      specimens, glomerular SCD-1 induction was observed in podocytes of patients with
      diabetic nephropathy. Functionally, the liver X receptor agonists TO901317 and
      GW3965, two known inducers of SCD, increased Scd-1 and Scd-2 expression in
      cultured podocytes and reduced palmitic acid-induced cell death. Similarly,
      overexpression of Scd-1 attenuated palmitic acid-induced cell death. The
      protective effect of TO901317 was associated with a reduction of endoplasmic
      reticulum stress. It was lost after gene silencing of Scd-1/-2, thereby
      confirming that the protective effect of TO901317 is mediated by Scd-1/-2.
      TO901317 also shifted palmitic acid-derived FFAs into biologically inactive
      triglycerides. In summary, SCD-1 up-regulation in diabetic nephropathy may be
      part of a protective mechanism against saturated FFA-derived toxic metabolites
      that drive endoplasmic reticulum stress and podocyte death. 

PMID- 23867798
TI  - RAMP1 is a direct NKX3.1 target gene up-regulated in prostate cancer that
      promotes tumorigenesis.
AB  - The homeodomain-containing transcription factor, NKX3.1, plays an important role
      in the suppression of prostate tumorigenesis. Herein, we identify the receptor
      activity-modifying protein 1 (RAMP1) as a direct NKX3.1 target gene through
      analysis of chromatin immunoprecipitation coupled to massively parallel
      sequencing and gene expression data. RAMP1 is a coreceptor for certain G-protein
      coupled receptors, such as the calcitonin gene-related peptide receptor, to the
      plasma membrane. We found that RAMP1 expression is specifically elevated in human
      prostate cancer relative to other tumor types. Furthermore, RAMP1 mRNA and
      protein levels are significantly higher in human prostate cancer compared with
      benign glands. We identified multiple NKX3.1 binding sites in the RAMP1 locus in
      human prostate cancer cells and in the normal mouse prostate. Analyses of Nkx3.1
      knockout mice and human prostate cancer cell lines indicate that NKX3.1 represses
      RAMP1 expression. Knockdown of RAMP1 by shRNA decreased prostate cancer cell
      proliferation and tumorigenicity in vitro and in vivo. By using gene expression
      profiling and pathway analyses, we identified several cancer-related pathways
      that are significantly altered in RAMP1 knockdown cells, including the mitogen
      activated protein kinase signaling pathway. Further experiments confirmed a
      reduction in MAP2KI (MEK1) expression and phosphorylated-extracellular signal
      regulated kinase 1/2 levels in RAMP1 knockdown cells. These data provide novel
      insights into the role of RAMP1 in promoting prostate tumorigenesis and support
      the potential of RAMP1 as a novel biomarker and possible therapeutic target in
      prostate cancer. 

PMID- 23867800
TI  - Understanding the role of phase in chemical bond breaking with coincidence
      angular streaking.
AB  - Electron motion in chemical bonds occurs on an attosecond timescale. This
      ultrafast motion can be driven by strong laser fields. Ultrashort asymmetric
      laser pulses are known to direct electrons to a certain direction. But do
      symmetric laser pulses destroy symmetry in breaking chemical bonds? Here we
      answer this question in the affirmative by employing a two-particle coincidence
      technique to investigate the ionization and fragmentation of H2 by a long
      circularly polarized multicycle femtosecond laser pulse. Angular streaking and
      the coincidence detection of electrons and ions are employed to recover the phase
      of the electric field, at the instant of ionization and in the molecular frame,
      revealing a phase-dependent anisotropy in the angular distribution of H+
      fragments. Our results show that electron localization and asymmetrical breaking
      of molecular bonds are ubiquitous, even in symmetric laser pulses. The technique
      we describe is robust and provides a powerful tool for ultrafast science.

PMID- 23867799
TI  - Gadolinium contrast agent-induced CD163+ ferroportin+ osteogenic cells in
      nephrogenic systemic fibrosis.
AB  - Gadolinium-based contrast agents are linked to nephrogenic systemic fibrosis in
      patients with renal insufficiency. The pathology of nephrogenic systemic fibrosis
      is characterized by abnormal tissue repair: fibrosis and ectopic ossification.
      The mechanisms by which gadolinium could induce fibrosis and ossification are not
      known. We examined in vitro the effect of a gadolinium-based contrast agent on
      human peripheral blood mononuclear cells for phenotype and function relevant to
      the pathology of nephrogenic systemic fibrosis using immunofluorescence, flow
      cytometry, real-time PCR, and osteogenic assays. We also examined tissues from
      patients with nephrogenic systemic fibrosis, using IHC to identify the presence
      of cells with phenotype induced by gadolinium. Gadolinium contrast induced
      differentiation of human peripheral blood mononuclear cells into a unique
      cellular phenotype--CD163(+) cells expressing proteins involved in fibrosis and
      bone formation. These cells express fibroblast growth factor (FGF)23, osteoblast
      transcription factors Runt-related transcription factor 2, and osterix, and show
      an osteogenic phenotype in in vitro assays. We show in vivo the presence of
      CD163(+)/procollagen-1(+)/osteocalcin(+) cells in the fibrotic and calcified
      tissues of nephrogenic systemic fibrosis patients. Gadolinium contrast-induced
      CD163(+)/ferroportin(+)/FGF23(+) cells with osteogenic potential may play a role
      in systemic fibrosis and ectopic ossification in nephrogenic systemic fibrosis.

PMID- 23867802
TI  - Cross-species approaches to pathological gambling: a review targeting sex
      differences, adolescent vulnerability and ecological validity of research tools.
AB  - Decision-making plays a pivotal role in daily life as impairments in processes
      underlying decision-making often lead to an inability to make profitable long
      term decisions. As a case in point, pathological gamblers continue gambling
      despite the fact that this disrupts their personal, professional or financial
      life. The prevalence of pathological gambling will likely increase in the coming
      years due to expanding possibilities of on-line gambling through the Internet and
      increasing liberal attitudes towards gambling. It therefore represents a growing
      concern for society. Both human and animal studies rapidly advance our knowledge
      on brain-behaviour processes relevant for understanding normal and pathological
      gambling behaviour. Here, we review in humans and animals three features of
      pathological gambling which hitherto have received relatively little attention:
      (1) sex differences in (the development of) pathological gambling, (2)
      adolescence as a (putative) sensitive period for (developing) pathological
      gambling and (3) avenues for improving ecological validity of research tools.
      Based on these issues we also discuss how research in humans and animals may be
      brought in line to maximize translational research opportunities. 

PMID- 23867801
TI  - Animal models and measures of perceptual processing in schizophrenia.
AB  - This paper summarizes the discussions regarding animal paradigms for assessing
      perception at the seventh meeting of the Cognitive Neuroscience Treatment
      Research to Improve Cognition in Schizophrenia (CNTRICS). A breakout group at the
      meeting addressed candidate tests in animals that might best parallel the human
      paradigms selected previously in the CNTRICS program to assess two constructs in
      the domain of perception: gain control and visual integration. The perception
      breakout group evaluated the degree to which each of the nominated tasks met pre
      specified criteria: comparability of tasks across multiple species; construct
      validity; neuroanatomical homology between species; and dynamic range across
      parametric variation. 

PMID- 23867803
TI  - Comparison of immunosuppressive and cytotoxic cells in angiosarcoma: development
      of a possible supportive therapy for angiosarcoma.
AB  - An imbalance of immunosuppressive and cytotoxic cells plays an important role in
      inhibiting the anti-tumor immune response of the tumor-bearing host. The purpose
      of this study was to elucidate the involvement of immunosuppressive cells, such
      as regulatory T cells and CD163+ M2 macrophages as well as cytotoxic cells, such
      as granulysin-bearing cells and TIA-1+ cells in cutaneous angiosarcoma (AS) by
      immunohistochemical staining. In addition we evaluated the potencies of
      bisphosphonate, which was previously reported to suppress the expression of
      matrix metalloproteinase 9 (MMP-9), as a supportive therapy for AS together with
      docetaxel in 6 cases of cutaneous AS. These findings suggest that a high number
      of immunosuppressive cells might be related to the prognosis of AS, and that a
      combination of docetaxel with bisphosphonate risedronate sodium might be
      effective for MMP-9-expressing AS.

PMID- 23867804
TI  - Deletions within the 3' non-translated region of Alfalfa mosaic virus RNA4 do not
      affect replication but significantly reduce long-distance movement of chimeric
      Tobacco mosaic virus.
AB  - Alfalfa mosaic virus (AlMV) RNAs 1 and 2 with deletions in their 3' non
      translated regions (NTRs) have been previously shown to be encapsidated into
      virions by coat protein (CP) expressed from RNA3, indicating that the 3' NTRs of
      RNAs 1 and 2 are not required for virion assembly. Here, we constructed various
      mutants by deleting sequences within the 3' NTR of AlMV subgenomic (sg) RNA4
      (same as of RNA3) and examined the effect of these deletions on replication and
      translation of chimeric Tobacco mosaic virus (TMV) expressing AlMV sgRNA4 from
      the TMV CP sg promoter (Av/A4) in tobacco protoplasts and Nicotiana benthamiana
      plants. While the Av/A4 mutants were as competent as the wild-type Av/A4 in RNA
      replication in protoplasts, their encapsidation, long-distance movement and virus
      accumulation varied significantly in N. benthamiana. These data suggest that the
      3' NTR of AlMV sgRNA4 contains potential elements necessary for virus
      encapsidation. 

PMID- 23867805
TI  - Complete nucleotide sequence of a South African isolate of Grapevine fanleaf
      virus and its associated satellite RNA.
AB  - The complete sequences of RNA1, RNA2 and satellite RNA have been determined for a
      South African isolate of Grapevine fanleaf virus (GFLV-SACH44). The two RNAs of
      GFLV-SACH44 are 7,341 nucleotides (nt) and 3,816 nt in length, respectively, and
      its satellite RNA (satRNA) is 1,104 nt in length, all excluding the poly(A) tail.
      Multiple sequence alignment of these sequences showed that GFLV-SACH44 RNA1 and
      RNA2 were the closest to the South African isolate, GFLV-SAPCS3 (98.2% and 98.6%
      nt identity, respectively), followed by the French isolate, GFLV-F13 (87.3% and
      90.1% nt identity, respectively). Interestingly, the GFLV-SACH44 satRNA is more
      similar to three Arabis mosaic virus satRNAs (85%-87.4% nt identity) than to the
      satRNA of GFLV-F13 (81.8% nt identity) and was most distantly related to the
      satRNA of GFLV-R2 (71.0% nt identity). Full-length infectious clones of GFLV
      SACH44 satRNA were constructed. The infectivity of the clones was tested with
      three nepovirus isolates, GFLV-NW, Arabis mosaic virus (ArMV)-NW and GFLV-SAPCS3.
      The clones were mechanically inoculated in Chenopodium quinoa and were infectious
      when co-inoculated with the two GFLV helper viruses, but not when co-inoculated
      with ArMV-NW. 

PMID- 23867806
TI  - Why are manuscripts rejected after submission to Folia Phoniatrica et
      Logopaedica?

PMID- 23867807
TI  - Linear and non-linear analysis of heart rate variability in master athletes and
      healthy middle-aged non-athletes.
AB  - The present study examined the autonomic cardiac modulation of veteran athletes
      by the use of traditional and modern methods of heart rate variability (HRV)
      analysis. Twenty-nine healthy male master soccer players were divided into two
      groups; group A consisted of fourteen participants (age 48.9+/-5.8 years), who
      were engaged to regular aerobic exercise and group B of fifteen sedentary ones
      (age 50.8+/-5.7 years). Sixteen age-matched non-athletes formed control group C.
      All participants underwent ambulatory 24-h continuous electrocardiogram
      monitoring for the calculation of time and frequency domain HRV indices.
      Additionally, Poincare analysis SD1 and SD2 as well as multiresolution wavelet
      analysis sigmawav(16) and sigmawav(32) markers were calculated. Time-domain
      indices were significantly increased in group A compared to groups B and C. Group
      A presented greater values of SD1 (by 43%, p<0.01 and 34.4%, p<0.05 than groups B
      and C respectively) and SD2 (by 26% compared to B and by 34.1% to C, p<0.05).
      Index sigmawav(16) was higher in group A than in B and C by 35.6% (p<0.01) and
      23.5% (p<0.05) respectively and so did sigmawav(32) by 22% (p<0.05) and 24%
      (p<0.05). Strong correlations were reported among indices. In conclusion,
      physically active master athletes attain better cardiac autonomic activity than
      sedentary counterparts, as proved by the application of Poincare and
      multiresolution wavelet analyses, which can be useful research tools of cardiac
      autonomic modulation in sports cardiology.

PMID- 23867808
TI  - Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the
      ENLIGHTEN study.
AB  - BACKGROUND: QVA149 is an inhaled, once-daily fixed-dose dual bronchodilator
      combination of the long-acting beta2-agonist indacaterol and long-acting
      muscarinic antagonist glycopyrronium (NVA237) for the treatment of chronic
      obstructive pulmonary disease (COPD). We investigated the safety and efficacy of
      QVA149 over 52 weeks. METHODS: This 52-week, multicenter, double-blind, parallel
      group, placebo-controlled study randomized (2:1) patients with moderate-to-severe
      COPD to once-daily QVA149 (110 MUg indacaterol/50 MUg glycopyrronium) or placebo
      delivered via the Breezhaler device. Primary endpoint was safety and tolerability
      for treatment-emergent adverse events (AEs). Secondary endpoints included safety
      based on vital signs, electrocardiograms (ECGs), laboratory evaluations, and pre
      dose forced expiratory volume in 1 s (FEV1). RESULTS: Of 339 patients randomized,
      QVA149 [n = 226], placebo [n = 113]; 76.9% male, mean age: 62.6 years, post
      bronchodilator FEV1: 57.4% predicted, 83.5% completed study. A smaller percentage
      of patients discontinued in the QVA149 group (14.2%) compared with placebo
      (21.2%). Overall incidence of AEs was similar in the QVA149 (57.8%) and placebo
      (56.6%) groups, with most AEs being mild to moderate in severity. The numerical
      differences in some AEs observed could be at least in part explained by
      differences in baseline patient characteristics. No clinically relevant
      differences were observed between treatment groups for vital signs or ECG
      parameters. The five deaths reported were unrelated to study medication (QVA149,
      n = 4 [1.8%]; placebo, n = 1 [0.9%]). QVA149 demonstrated rapid and clinically
      meaningful bronchodilation sustained over 52 weeks versus placebo. CONCLUSION:
      QVA149 demonstrated a good safety and tolerability profile, providing rapid and
      sustained bronchodilation over 52 weeks in patients with moderate-to-severe COPD.
      ClinicalTrials.gov identifier: NCT01120717.

PMID- 23867809
TI  - The minimal important difference of the King's Brief Interstitial Lung Disease
      Questionnaire (K-BILD) and forced vital capacity in interstitial lung disease.
AB  - Health status and forced vital capacity (FVC) are widely used outcome measures of
      interstitial lung disease (ILD) but there is a paucity of studies reporting the
      minimal clinically meaningful change in these parameters. A study was undertaken
      to assess the minimal important difference (MID) of an ILD specific health status
      questionnaire, the King's Brief ILD questionnaire (K-BILD) and that of FVC in a
      range of ILDs. 57 patients with ILD (17 idiopathic pulmonary fibrosis; IPF)
      completed the K-BILD (score range 0-100) at 2 separate clinic visits. Patients
      underwent spirometry at both visits. The MID was determined by a range of
      distribution methods (Standard error of mean: SEM and 0.3* Effect size: ES) and
      anchor based methods (objective: FVC and subjective: global rating of change
      questionnaires, GRCQ). The MID was derived by calculating an average of all
      methods. Health status was reduced at baseline in all patients, mean (SD) K-BILD
      total score 62(23). The average MID for K-BILD total score incorporating all
      methods was an 8 unit change (range 6-10). The average MID for FVC was a 6%
      change of baseline (range 4-7%). The K-BILD is a responsive patient reported
      outcome measure for patients with ILD. It can potentially be used to assess
      patients in the clinic and evaluate the response to therapy. The MID of the K
      BILD total score is 8 units. The MID for FVC for a range of ILDs was 6%, similar
      to that reported recently for patients with IPF. Our findings will facilitate the
      clinical interpretation of health status and FVC data in ILD. 

PMID- 23867811
TI  - DNA methylation as a long-term biomarker of exposure to tobacco smoke.
AB  - BACKGROUND: Most biomarkers of exposure tend to have short half-lives. This
      includes cotinine, a metabolite of nicotine widely used to assess smoke exposure.
      Cotinine is thus unsuitable as a determinant of past exposure to cigarette smoke.
      METHODS: We used bisulphite pyrosequencing of a set of four genomic loci (AHRR,
      6p21, and two at 2q37) that had differential DNA methylation levels in peripheral
      blood DNA dependent on tobacco exposure to create a predictive model of smoking
      status. RESULTS: Combining four gene loci into a single methylation index
      provided high positive predictive and sensitivity values for predicting former
      smoking status in both test (n = 81) and validation (n = 180) sample sets.
      CONCLUSIONS: This study provides a direct molecular measure of prior exposure to
      tobacco that can be performed using the quantitative approach of bisulphite
      pyrosequencing. Epigenetic changes that are detectable in blood may more
      generally act as molecular biomarkers for other exposures that are also difficult
      to quantify in epidemiological studies.

PMID- 23867812
TI  - Medical product safety surveillance: how many databases to use?
AB  - Large linked database networks, like the US Food and Drug Administration's
      Sentinel System, are being built for medical product surveillance. One use of
      these networks is for "near real-time" sequential database surveillance of
      prespecified medical product-adverse event pairs, which may result in a "safety
      signal" when a statistical excess risk is detected. Sequential database
      surveillance requires the investigator to manage surveillance in both information
      time (ie, how sample size accrues) and calendar time. Calendar time is important
      because people external to the surveillance population may be affected by the
      speed with which a safety signal is detected or ruled out. Optimal design and
      analysis aspects of sequential database surveillance are not well developed, but
      are gaining in importance as observational database networks grow. Using
      information time concepts, we show how to calculate sample sizes when performing
      sequential database surveillance, illustrating the relationships between
      statistical power, the time to detect a signal, and the maximum sample size for
      various true effect sizes. Then, using a vaccine example, we demonstrate a four
      step planning process that allows investigators to translate information time
      into calendar time. Given the calendar time for surveillance, the process focuses
      on choosing observational database configurations consistent with the
      investigator's preferences for timeliness and statistical power. Although the
      planning process emphasizes sample size considerations, the influence of
      secondary database attributes such as delay times, measurement error, and cost
      are also discussed. Appropriate planning allows the most efficient use of public
      health dollars dedicated to medical product surveillance efforts.

PMID- 23867810
TI  - Neural networks in intestinal immunoregulation.
AB  - Key physiological functions of the intestine are governed by nerves and
      neurotransmitters. This complex control relies on two neuronal systems: an
      extrinsic innervation supplied by the two branches of the autonomic nervous
      system and an intrinsic innervation provided by the enteric nervous system. As a
      result of constant exposure to commensal and pathogenic microflora, the intestine
      developed a tightly regulated immune system. In this review, we cover the current
      knowledge on the interactions between the gut innervation and the intestinal
      immune system. The relations between extrinsic and intrinsic neuronal inputs are
      highlighted with regards to the intestinal immune response. Moreover, we discuss
      the latest findings on mechanisms underlying inflammatory neural reflexes and
      examine their relevance in the context of the intestinal inflammation. Finally,
      we discuss some of the recent data on the identification of the gut microbiota as
      an emerging player influencing the brain function. 

PMID- 23867814
TI  - Leisure time physical activity and mortality.
AB  - BACKGROUND: Some studies indicate that a large part of the beneficial effect of
      physical activity on mortality is confined to a threshold effect of
      participation. METHODS: Self-reported physical activity was investigated in
      relation to all-cause mortality in the Danish Diet, Cancer and Health cohort,
      including 29,129 women and 26,576 men aged 50-64 years at baseline 1993-1997.
      Using Cox proportional hazards models we investigated the associations between
      mortality rate and leisure time physical activity by exploring 1) participation
      (yes/no) in each type of activity; 2) a simple dose-response relationship with
      hours spent on each activity, supplemented with indicators of participation in
      each activity; and 3) inflexion or nonmonotonic dose-response relationships using
      linear splines. RESULTS: A total of 2696 women and 4044 men died through March
      2010. We found lower mortality with participation in sports (for women, mortality
      rate ratio = 0.75, 95% confidence interval = 0.69-0.81; for men, 0.78, 0.73
      0.84), cycling (for women, 0.77, 0.71-0.84; for men, 0.90, 0.84-0.96), or
      gardening (for women, 0.84, 0.78-0.91; for men, 0.73, 0.68-0.79) and in men
      participating in do-it-yourself activity (0.77, 0.71-0.84). A weak adverse dose
      response was seen for walking and gardening, but the association was small (1-2%
      increase in mortality per additional hour). We found no signs of inflexion or
      nonmonotonic effects of additional hours spent on each activity. CONCLUSION:
      Mortality was lower with participation in specific leisure time physical
      activities, but not with more time spent on those activities. This could suggest
      that avoiding a sedative lifestyle is more important than a high volume of
      activity. Nonparticipation in these types of physical activity may be considered
      as risk factors.

PMID- 23867813
TI  - Early growth patterns in children with autism.
AB  - BACKGROUND: Case-control studies have found increased head growth during the
      first year of life in children with autism spectrum disorder. Length and weight
      have not been as extensively studied, and there are few studies of population
      based samples. METHODS: The study was conducted in a sample of 106,082 children
      from the population-based Norwegian Mother and Child Cohort. The children were
      born in 1999-2009; by the end of follow-up on 31 December 2012, the age range was
      3.6 through 13.1 years (mean 7.4 years). Measures were obtained prospectively
      until age 12 months for head circumference and 36 months for length and weight.
      We compared growth trajectories in autism spectrum disorder cases and noncases
      using Reed first-order models. RESULTS: Subjects included 376 children (310 boys
      and 66 girls) with specialist-confirmed autism spectrum disorder. In boys with
      autism spectrum disorder, mean head growth was similar to that of other boys, but
      variability was greater, and 8.7% had macrocephaly (head circumference > 97th
      cohort percentile) by 12 months of age. Autism spectrum disorder boys also had
      slightly increased body growth, with mean length 1.1 cm above and mean weight 300
      g above the cohort mean for boys at age 12 months. Throughout the first year, the
      head circumference of girls with autism spectrum disorder was reduced-by 0.3 cm
      at birth and 0.5 cm at 12 months. Their mean length was similar to that of other
      girls, but their mean weight was 150-350 g below at all ages from birth to 3
      years. The reductions in mean head circumference and weight in girls with autism
      spectrum disorder appear to be driven by those with intellectual disability,
      genetic disorders, and epilepsy. DISCUSSION: Growth trajectories in children with
      autism spectrum disorder diverge from those of other children and the differences
      are sex specific. Previous findings of increased mean head growth were not
      replicated.

PMID- 23867815
TI  - HIV gp120 induced gene expression signatures in vaginal epithelial cells.
AB  - Gp120 is the envelope protein of HIV which binds to CD4 independent proteins on
      vaginal epithelial cells. HIV-gp120 has been reported to modulate gene expression
      in several cell types. How this interaction may alter the physiologic vaginal
      milieu during the earliest stages of vaginal transmission of HIV, is currently
      unknown. Vaginal epithelial cells were treated with HIV-gp120, and a global
      snapshot of changes in gene expression profiles, were unraveled by microarray
      analysis. The differentially expressed genes were involved in diverse cellular
      functions. Genes of immunomodulatory processes and induction of proteases were
      highly enriched. We propose that the induction of inflammation and proteases may
      act in concert to weaken the vaginal epithelium, making it more permeable to
      viral entry. Identification of the gene signatures involved in vaginal-HIV
      dialogue would aid in understanding the environ induced by HIV itself, as the
      virus invades and gains entry into its host. 

PMID- 23867817
TI  - Heptachlor induced mitochondria-mediated cell death via impairing electron
      transport chain complex III.
AB  - Environmental toxins like pesticides have been implicated in the pathogenesis of
      Parkinson's disease (PD). Epidemiological studies suggested that exposures to
      organochlorine pesticides have an association with an increased PD risk. In the
      present study, we examined the mechanism of toxicity induced by an organochlorine
      pesticide heptachlor. In a human dopaminergic neuroblastoma SH-SY5Y cells,
      heptachlor induced both morphological and functional damages in mitochondria.
      Interestingly, the compound inhibited mitochondrial electron transport chain
      complex III activity. Rapid generation of reactive oxygen species and the
      activation of Bax were then detected. Subsequently, mitochondria-mediated,
      caspase-dependent apoptosis followed. Our results raise a possibility that an
      organochlorine pesticide heptachlor can act as a neurotoxicant associated with
      PD.

PMID- 23867816
TI  - Four new diterpenes from Aphanamixis polystachya.
AB  - Four novel diterpenes possessing rare five-membered peroxide ring,
      aphanaperoxides E-H (1-4), were isolated from stem bark of Aphanamixis
      polystachya. Their structures including the absolute configuration were
      elucidated by spectroscopic data and CD analysis. The cytotoxicities of the
      isolated compounds against a panel of human cancer cell lines were evaluated. 

PMID- 23867818
TI  - Cathelicidin antimicrobial peptide inhibits fibroblast migration via P2X7
      receptor signaling.
AB  - Fibrosis is one of the most common pathological alterations in heart failure, and
      fibroblast migration is an essential process in the development of cardiac
      fibrosis. Experimental autoimmune myocarditis (EAM) is a model of inflammatory
      heart disease characterized by inflammatory cell infiltration followed by healing
      without residual fibrosis. However, the precise mechanisms mediating termination
      of inflammation and nonfibrotic healing remain to be elucidated. Microarray
      analysis of hearts from model mice at multiple time points after EAM induction
      identified several secreted proteins upregulated during nonfibrotic healing,
      including the anti-inflammatory cathelicidin antimicrobial peptide (CAMP).
      Treatment with LL-37, a human homolog of CAMP, activated MAP kinases in
      fibroblasts but not in cardiomyocytes, indicating that fibroblasts were the
      target of CAMP activity. In addition, LL-37 decreased fibroblast migration in the
      in vitro scratch assay. P2X7 receptor (P2X7R), a well-known receptor for LL-37,
      was involved in LL-37 mediated biological effect on cardiac fibroblasts.
      Stimulation of BzATP, a P2X7R agonist, activated MAPK in fibroblasts, whereas the
      P2X7R antagonist, BBG, as well as P2X7R deletion abolished both LL-37-mediated
      MAPK activation and LL-37-induced reduction in fibroblast migration. These
      results strongly suggest that CAMP upregulation during myocarditis prevents
      myocardial fibrosis by restricting fibroblast migration via activation of the
      P2X7R-MAPK signaling pathway.

PMID- 23867819
TI  - Glutathione S-transferase omega suppresses the defective phenotypes caused by
      PINK1 loss-of-function in Drosophila.
AB  - Loss-of-function mutation of the PTEN-induced kinase 1 (PINK1) gene is a common
      cause of early-onset Parkinson's disease (PD). Glutathione S-transferase omega
      (GSTO) is a phase II detoxification enzyme that conjugates targets to
      glutathione, and has recently been implicated in parkin-associated PD. In this
      study, we found Drosophila GstO2 to be a novel genetic suppressor of the PINK1
      loss-of-function mutant. We show that GstO2A expression is reduced in PINK1
      mutants. Moreover, the upregulation of GstO2A restores muscle degeneration and
      dopaminergic neuron loss in PINK1 mutants. Given the previous data of a reduced
      expression of GstO2A and decreased glutathionylation of ATP synthase beta subunit
      in parkin or PINK1 mutants, these results suggest that the function of GstO2 is
      regulated by the PINK1/parkin pathway and that GstO2 also has a protective role
      in PINK1-associated PD.

PMID- 23867820
TI  - Key role of microRNA-15a in the KLF4 suppressions of proliferation and
      angiogenesis in endothelial and vascular smooth muscle cells.
AB  - While recent insights indicate that the transcription factor Kruppel-like factor
      4 (KLF4) is indispensable for vascular homeostasis, its exact role in
      proliferation and angiogenesis and how it functions remain unresolved. Thus, the
      aim of the present study was to evaluate the role of KLF4 in the proliferations
      of endothelial and vascular smooth muscle cells, as well as the angiogenesis. The
      overexpression of KLF4 in endothelial cells significantly impaired tube
      formation. KLF4 inhibited the formation of a vascular network in implanted
      Matrigel plugs in nude mice. Importantly, we found that KLF4 significantly
      upregulated the miR-15a expression in endothelial cells and vascular smooth
      muscle cells, and conversely, KLF4 depletion reduced the amount of miR-15a.
      Furthermore, KLF4 blocked cell cycle progression and decreased cyclin D1
      expression in endothelial cells and vascular smooth muscle cells through the
      induction of miR-15a. Intriguingly, the delivery of a miR-15a antagomir to nude
      mice resulted in marked attenuation of the anti-angiogenic effect of KLF4.
      Collectively, our present study provide the first evidence that miR-15a as a
      direct transcriptional target of KLF4 that mediates the anti-proliferative and
      anti-angiogenic actions of KLF4, which indicates that KLF4 upregulation of miR
      15a may represent a therapeutic option to suppress proliferative vascular
      disorders.

PMID- 23867821
TI  - Reactivation of AKT signaling following treatment of cancer cells with PI3K
      inhibitors attenuates their antitumor effects.
AB  - Targeting the phosphatidylinositol-3-kinase (PI3K) is a promising approach in
      cancer therapy. In particular, PI3K blockade leads to the inhibition of AKT, a
      major downstream effector responsible for the oncogenic activity of PI3K.
      However, we report here that small molecule inhibitors of PI3K only transiently
      block AKT signaling. Indeed, treatment of cancer cells with PI3K inhibitors
      results in a rapid inhibition of AKT phosphorylation and signaling which is
      followed by the reactivation of AKT signaling after 48 h as observed by Western
      blot. Reactivation of AKT signaling occurs despite effective inhibition of PI3K
      activity by PI3K inhibitors. In addition, wortmannin, a broad range PI3K
      inhibitor, did not block AKT reactivation suggesting that AKT signals
      independently of PI3K. In a therapeutical perspective, combining AKT and PI3K
      inhibitors exhibit stronger anti-proliferative and pro-apoptotic effects compared
      to AKT or PI3K inhibitors alone. Similarly, in a tumor xenograft mouse model,
      concomitant PI3K and AKT blockade results in stronger anti-cancer activity
      compared with either blockade alone. This study shows that PI3K inhibitors only
      transiently inhibit AKT which limits their antitumor activities. It also provides
      the proof of concept to combine PI3K inhibitors with AKT inhibitors in cancer
      therapy.

PMID- 23867822
TI  - Romo1 expression contributes to oxidative stress-induced death of lung epithelial
      cells.
AB  - Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an
      important role in pathogenesis in lung diseases such as idiopathic pulmonary
      fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial
      cell death is not fully understood. Reactive oxygen species (ROS) modulator 1
      (Romo1) is localized in the mitochondria and mediates mitochondrial ROS
      production through complex III of the mitochondrial electron transport chain.
      Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis
      induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H2O2)
      treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular
      ROS levels and cell death triggered by H2O2 treatment. In immunohistochemical
      staining of lung tissues from patients with IPF, Romo1 was mainly localized in
      hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was
      detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells
      were also detected in most patients with IPF but not in normal controls. These
      findings suggest that Romo1 mediates apoptosis induced by oxidative stress in
      lung epithelial cells. 

PMID- 23867823
TI  - Single particle tracking of dynamically localizing TatA complexes in Streptomyces
      coelicolor.
AB  - The Tat (twin-arginine translocation) pathway transports folded proteins across
      the bacterial cytoplasmic membrane and is a major route of protein export in the
      mycelial soil-dwelling bacterium Streptomyces. We recently examined the
      localization of Tat components (TatABC) in time-lapse imaging and demonstrated
      that all three components colocalize dynamically with a preference for apical
      sites. Here we apply an in-house single particle tracking package to
      quantitatively analyze the movement of the TatA subunit, the most abundant of the
      Tat components. Segmentation and analysis of trajectories revealed that TatA
      transitions from free to confined movement and then to fixed localization. The
      sequence starts with a mixed punctate and dispersed localization of TatA
      oligomers, which then develop into a few larger still foci, and finally
      colocalize with TatBC to form a functional translocation system. It takes 15-30
      min for the Tat export complex to assemble and most likely become active. With
      this study we provide the first example of quantitative analysis of dynamic
      protein localization in Streptomyces, which is applicable to the study of many
      other dynamically localizing proteins identified in these complex bacteria.

PMID- 23867824
TI  - Role of cathepsin B in dengue virus-mediated apoptosis.
AB  - Dengue virus (DENV) infection is one of the most important mosquito-borne viral
      diseases, which is endemic in the tropical and sub-tropical regions. Patients
      with dengue hemorrhagic fever (DHF) generally present hemorrhagic tendencies,
      plasma leakage, thrombocytopenia, and hemoconcentration. Hepatic dysfunction is
      also a crucial feature of DENV infection. Hepatic biopsy specimens obtained from
      fatal cases of DENV infection show cellular apoptosis, which apparently relate to
      the pathogenesis. Cathepsins, which are cysteine proteases inside the lysosome,
      were previously reported to be up-regulated in patients with DHF. However, their
      functions during DENV infection have not been thoroughly investigated. We show
      for the first time that DENV induces lysosomal membrane permeabilization. The
      resulting cytosolic cathepsin B and S contributed to apoptosis via caspase
      activation. The activity of caspase 3 was significantly reduced in DENV-infected
      HepG2 cells treatedwith cathepsin B or S inhibitors. Treatment with cathepsin B
      inhibitor also reduced the activity of caspase 9, suggesting that cathepsin B
      activates both caspase-9 and caspase-3. Reduced cathepsin B expression, effected
      by RNA interference, mimicked pharmacological inhibition of the enzyme and
      confirmed the contribution of cathepsin B to apoptotic events induced by DENV in
      HepG2 cells. 

PMID- 23867825
TI  - The effect of valinomycin in fibroblasts from patients with fatty acid oxidation
      disorders.
AB  - Disorders of the carnitine cycle and of the beta oxidation spiral impair the
      ability to obtain energy from fats at time of fasting and stress. This can result
      in hypoketotic hypoglycemia, cardiomyopathy, cardiac arrhythmia and other chronic
      medical problems. The in vitro study of fibroblasts from patients with these
      conditions is impaired by their limited oxidative capacity. Here we evaluate the
      capacity of valinomycin, a potassium ionophore that increases mitochondrial
      respiration, to increase the oxidation of fatty acids in cells from patients with
      inherited fatty acid oxidation defects. The addition of valinomycin to
      fibroblasts decreased the accumulation of the lipophilic cation
      tetraphenylphosphonium (TPP(+)) at low concentrations due to the dissipation of
      the mitochondrial membrane potential. At higher doses, valinomycin increased
      TPP(+) accumulation due to the increased potassium permeability of the plasma
      membrane and subsequent cellular hyperpolarization. The incubation of normal
      fibroblasts with valinomycin increased [(14)C]-palmitate oxidation (measured as
      [(14)C]O2 release) in a dose-dependent manner. By contrast, valinomycin failed to
      increase palmitate oxidation in fibroblasts from patients with very long chain
      acyl CoA dehydrogenase (VLCAD) deficiency. This was not observed in fibroblasts
      from patients heterozygous for this condition. These results indicate that
      valinomycin can increase fatty acid oxidation in normal fibroblasts and could be
      useful to differentiate heterozygotes from patients affected with VLCAD
      deficiency.

PMID- 23867826
TI  - Analyses in human urothelial cells identify methylation of miR-152, miR-200b and
      miR-10a genes as candidate bladder cancer biomarkers.
AB  - Urinary miRNAs are discussed as potential biomarkers for bladder cancer. The
      majority of miRNAs, however, are downregulated, making it difficult to utilize
      reduced miRNA signals as reliable diagnostic tools. Because the downregulation of
      miRNAs is frequently associated with hypermethylation of the respective
      regulative sequences, we studied whether DNA hypermethylation might serve as an
      improved diagnostic tool compared to measuring downregulated miRNAs. miRNA
      expression arrays and individual qPCR were used to identify and confirm miRNAs
      that were downregulated in malignant urothelial cells (RT4, 5637 and J82) when
      compared to primary, non-malignant urothelial cells (HUEPC). DNA methylation was
      determined by customized PCR-arrays subsequent to methylation-sensitive DNA
      restriction and by mass spectrometry. miRNA expression and DNA methylation were
      determined in untreated cells and in cultures treated with the demethylating
      agent 5-Aza-2'-deoxycytidine. miR-200b, miR-152 and miR-10a displayed
      differential expression and methylation among untreated cancer cell lines. In
      addition, reduced miRNA expression of miR-200b, miR-152, and miR-10a was
      associated with increased DNA methylation in malignant cells versus HUEPC.
      Finally, the demethylation approach revealed a causal relationship between both
      parameters for miR-152 in 5637 and also suggests a causal connection of both
      parameters for miR-200b in J82 and miR-10a in 5637. In conclusion, our studies in
      multiple bladder cancer cell lines and primary non-malignant urothelial cells
      suggest that hypermethylation of miR-152, miR-10a and miR-200b regulative DNA
      sequences might serve as epigenetic bladder cancer biomarkers. 

PMID- 23867827
TI  - Differential DNA methylation patterns in the CD86 gene controls its constitutive
      expression in keratinocytes.
AB  - The interaction of B7 family members with appropriate receptors is essential for
      an effective T cell response. CD80 and CD86 are the principal co-stimulatory
      molecules of this family and they are mainly expressed on professional antigen
      presenting cells (APCs), but also on several non-lymphoid cells. CD86 is
      constitutively expressed in keratinocytes from the spinous layer of normal
      cervical epithelium. However, the mechanisms that control the expression of this
      gene in epithelial cells remain unknown. We analyzed the DNA methylation status
      of the CD86 promoter and a CpG island located in the upstream intergenic region
      in keratinocyte-derived cell lines. In those cell lines where CD86 is expressed,
      a high degree of methylation in the CpG island was observed. However, a CpG
      dinucleotide within the cAMP response element (CRE) in the promoter region was
      consistently unmethylated and associated to the transcription factor CREB, as
      demonstrated by ChIP assays. The opposite methylation pattern was observed in
      cell lines where CD86 is not expressed, affecting also the binding of CREB. The
      analysis of the DNA methylation pattern of this gene in cells from the spinous
      and basal layers of normal cervical epithelium showed a similar profile to that
      observed in cell lines with and without expression of CD86 respectively. Our
      results indicate that the methylation pattern in the CD86 promoter and CpG island
      is closely related to the expression of this co-stimulatory molecule in
      keratinocytes. 

PMID- 23867828
TI  - Identification of pheromone-like compounds in male reproductive organs of the
      oriental locust Locusta migratoria.
AB  - Despite the great economical interest of locusts in agriculture, knowledge on
      their chemoreception systems is still poor. Phenylacetonitrile is recognised as a
      pheromone of the desert locust Schistocerca gregaria, triggering gregarization,
      promoting aggregation and inhibiting courtship. However, in the other major
      locust species, Locusta migratoria, pheromones have not been reported. We have
      identified the two isomers of naphthylpropionitrile from the male reproductive
      organs of L. migratoria. Chemical synthesis has confirmed the identity of the two
      compounds. Both isomers show significant affinity to CSP91, a protein reported in
      the testis, but not to three other proteins of the same family (CSP180, CSP540
      and CSP884) expressed in female accessory glands. The striking similarity of
      these compounds with phenylacetonitrile and the unusual nature of such chemicals
      strongly suggest that naphthylpropionitrile could be pheromones for L.
      migratoria, while their site of expression and binding activity indicate a role
      in communication between sexes.

PMID- 23867829
TI  - LC-ESI-MS method for the determination of dexamethasone acetate in skin of nude
      mouse.
AB  - A high-performance liquid chromatography-positive electrospray ionization single
      quadrupole mass spectrometric (LC-ESI-MS) method for the determination of
      dexamethasone acetate in skin of nude mouse using triamcinolone acetonide acetate
      as the internal standard (I.S.) was developed and fully validated. Both compounds
      were precipitated from skin homogenate with methanol and were separated by HPLC
      on a Shimadzu Shim-pack VP-ODS C18 column (150mm*2.0mm, 5MUm) with a mobile phase
      of methanol-water (80:20, v/v) at a flow rate of 0.2mL/min. Calibration curves
      were linear over the range of 0.05-5MUg/mL. The intra-run relative standard
      deviations were less than 9.59%. The inter-run relative standard deviations were
      less than 7.82%. The mean recovery was in the ranges of 89.95-95.97%,
      respectively. The method was successfully applied to determinate the
      concentration of dexamethasone acetate in skin and study the percutaneous
      absorption process in skin of nude mouse. 

PMID- 23867831
TI  - A green lead hydrometallurgical process based on a hydrogen-lead oxide fuel cell.
AB  - The automobile industry consumed 9 million metric tons of lead in 2012 for lead
      acid batteries. Recycling lead from spent lead-acid batteries is not only related
      to the sustainable development of the lead industry, but also to the reduction of
      lead pollution in the environment. The existing lead pyrometallurgical processes
      have two main issues, toxic lead emission into the environment and high energy
      consumption; the developing hydrometallurgical processes have the disadvantages
      of high electricity consumption, use of toxic chemicals and severe corrosion of
      metallic components. Here we demonstrate a new green hydrometallurgical process
      to recover lead based on a hydrogen-lead oxide fuel cell. High-purity lead, along
      with electricity, is produced with only water as the by-product. It has a >99.5%
      lead yield, which is higher than that of the existing pyrometallurgical processes
      (95-97%). This greatly reduces lead pollution to the environment. 

PMID- 23867830
TI  - Anti-oxidative and anti-inflammatory effects of 2-cyclopropylimino-3-methyl-1,3
      thiazoline hydrochloride on glutamate-induced neurotoxicity in rat brain.
AB  - In a previous in vitro study, we demonstrated the protective effects of a new
      drug, 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (KHG26377),
      against glutamate-induced excitotoxicity in cultured glial cells. In this study,
      we explored the possible mechanisms underlying the neuroprotective and anti
      inflammatory effects of this compound against glutamate-induced excitotoxicity in
      rat brain. Our results showed that pretreatment with KHG26377 significantly
      attenuated glutamate-induced elevation of lipid peroxidation, TNF-alpha, IFN
      gamma, nitric oxide, reactive oxygen species, NADPH oxidase, and Ca(2+) levels,
      as well as the expression of caspase-3, neuronal nitric oxide synthase, and pERK.
      Furthermore, KHG26377 pretreatment attenuated key antioxidant parameters such as
      levels of superoxide dismutase, catalase, glutathione, glutathione peroxidase,
      and glutathione reductase, and also mitigated suppression of mitochondrial
      transmembrane potential by glutamate toxicity. Thus, through its antioxidant and
      anti-inflammatory activities in rat brain, KHG26377 may help protect against
      glutamate-induced neuronal damage. 

PMID- 23867832
TI  - Treatment of a patient with multiple cutaneous piloleiomyoma-related pain with a
      local injection of triamcinolone acetonide.
AB  - BACKGROUND: Multiple cutaneous piloleiomyomas are rare, frequently painful and
      difficult-to-treat benign tumours originating in the arrectores pilorum muscles
      of the hair follicles. OBJECTIVE: The aim of this study was to determine the
      efficacy of a local injection of triamcinolone acetonide in relieving cutaneous
      piloleiomyoma-related pain. METHODS: A patient with multiple painful
      piloleiomyomas was treated with weekly local injections of triamcinolone
      acetonide into the nodules and papules for 3 weeks. RESULTS: The patient's
      nodules and papules became smaller, and the pain disappeared. At 1-year follow
      up, there were no side effects, pain recurrence or significant enlargement of any
      of the injected lesions. CONCLUSION: Our study demonstrates that local injection
      of triamcinolone acetonide may be a promising new treatment option for multiple
      painful cutaneous piloleiomyomas.

PMID- 23867833
TI  - Evidence for the formation of symmetric and asymmetric DLPC-DAPC lipid bilayer
      domains.
AB  - BACKGROUND/AIMS: We investigated if mixtures of the phosphatidylcholine (PC)
      lipids 1,2-dilauroyl-sn-glycero-3-phosphocholine (C12:0 PC; DLPC) and 1,2
      diarachidoyl-sn-glycero-3-phosphocholine (C20:0 PC; DAPC), which differ by eight
      methylene groups in acyl chain length, lead to the spontaneous formation of
      distinct lipid rafts and asymmetric bilayers. METHODS: The experiments were
      performed using Atomic Force Microscopy (AFM). RESULTS: We show that DLPC and
      DAPC mixed at a molar ratio of 1:1 lead to the formation of single, double and
      triple bilayers with peaks at 6.14 +/- 0.11, 13.27 +/- 0.17 and 20.54 +/- 0.46
      nm, respectively (n=750). Within these formations discrete height steps of 0.92
      nm can be resolved (n=422). CONCLUSION: The most frequently observed height steps
      value of 0.92 nm matches best with the calculated mean lipid hydrophobic
      thickness difference for asymmetric C12:0 PC and C20:0 PC lipid bilayers of 0.88
      nm. This indicates the ability of DLPC and DAPC to form asymmetric lipid
      bilayers.

PMID- 23867835
TI  - Exploring diagonal gait using a forward dynamic three-dimensional chimpanzee
      simulation.
AB  - Primates are unusual among terrestrial quadrupedal mammals in that at walking
      speeds they prefer diagonal rather than lateral gaits. A number of reasons have
      been proposed for this preference in relation to the arboreal ancestry of modern
      primates: stability, energetic cost, neural control, skeletal loading, and limb
      interference avoiding. However, this is a difficult question to explore
      experimentally since most primates only occasionally use anything other than
      diagonal gaits. An alternative approach is to produce biologically realistic
      computer simulations of primate gait that enable the constraints of biomechanical
      loading and the energetics of different modes of locomotion to be explored. In
      this paper we describe such a model for the chimpanzee Pan troglodytes. The
      simulation is able to produce spontaneous quadrupedal locomotion, and the
      footfall sequences generated are split between lateral and diagonal footfall
      sequences with no obvious energetic benefit associated with either option.
      However, out of 10 successful simulation runs, 5 were lateral sequence/lateral
      couplet gaits indicating a preference for a specific lateral footfall sequence
      with a relatively tightly constrained phase difference between the fore- and
      hindlimbs. This suggests that the choice of diagonal walking gaits in chimpanzees
      is not a simple mechanical phenomenon and that diagonal walking gaits in primates
      are selected for by multiple factors. 

PMID- 23867834
TI  - Homeostatic model assessment indices in evaluation of insulin resistance and
      secretion in hemodialysis patients.
AB  - BACKGROUND: Some previous observations suggest that insulin resistance and
      glucose metabolism disturbances are frequent complications of chronic kidney
      disease. However, there are no conclusive studies on other indices of the
      effectiveness of insulin action in end-stage renal disease (ESRD) patients,
      including chronically hemodialysed (HD) ones. MATERIAL AND METHODS: The groups
      comprised 33 non-diabetic ESRD hemodialysed patients and 33 healthy controls
      matched for age, sex, and body mass index (BMI). In both groups, HOMA-%B, HOMA
      %S, HOMA-IR indices, and DI were calculated using HOMA1 and HOMA2 as measures of
      insulin resistance. The indices were also assessed in subgroups divided according
      to BMI. RESULTS: Mean fasting plasma glucose concentrations were lower in ESRD
      patients than in healthy persons (82.4+/-10.4 vs. 93.9+/-11.6, p=0.001). Fasting
      serum insulin concentrations were similar in both groups (median 6.8 vs. 6.0
      mU/l, p=0.698). HOMA1-%B values were higher in ESRD patients than controls
      (median 137.1 vs. 81.6, p=0.002). HOMA1-%S (median 75.6 vs. 71.5) and HOMA1-IR
      (median 1.3 vs. 1.4) values were not significantly different (p=0.264 and
      p=0.189, respectively). DI1 levels were higher for HD patients than for healthy
      subjects (median 1.16 vs. 0.53, p<0.001). In subgroup analysis, all statistically
      significant differences were restricted mainly to persons with BMI <25 kg/m2.
      Similar results as for the HOMA1 model were obtained for HOMA2. CONCLUSIONS: 1.
      HOMA beta-cell function is strongly correlated with HOMA insulin resistance in HD
      patients. 2. In non-diabetic ESRD hemodialysed patients, the HOMA indices and DI
      may be useful and important models in interpretation of glucose metabolism
      disturbances.

PMID- 23867836
TI  - Nanocontainers made of various materials with tunable shape and size.
AB  - Nanocontainers have great potentials in targeted drug delivery and nanospace
      confined reactions. However, the previous synthetic approaches exhibited limited
      control over the morphology, size and materials of the nanocontainers, which are
      crucial in practical applications. Here, we present a synthetic approach to multi
      segment linear-shaped nanopores with pre-designed morphologies inside anodic
      aluminium oxide (AAO), by tailoring the anodizing duration after a rational
      increase of the applied anodizing voltage and the number of voltage increase
      during Al foil anodization. Then, we achieve nanocontainers with designed
      morphologies, such as nanofunnels, nanobottles, nano-separating-funnels and
      nanodroppers, with tunable sizes and diverse materials of carbon, silicon,
      germanium, hafnium oxide, silica and nickel/carbon magnetic composite, by
      depositing a thin layer of materials on the inner walls of the pre-designed AAO
      nanopores. The strategy has far-reaching implications in the designing and large
      scale fabrication of nanocontainers, opening up new opportunities in
      nanotechnology applications. 

PMID- 23867837
TI  - Techno-economical optimization of Reactive Blue 19 removal by combined
      electrocoagulation/coagulation process through MOPSO using RSM and ANFIS models.
AB  - In this research, Response Surface Methodology (RSM) and Adaptive Neuro Fuzzy
      Inference System (ANFIS) models were applied for optimization of Reactive Blue 19
      removal using combined electrocoagulation/coagulation process through Multi
      Objective Particle Swarm Optimization (MOPSO). By applying RSM, the effects of
      five independent parameters including applied current, reaction time, initial dye
      concentration, initial pH and dosage of Poly Aluminum Chloride were studied.
      According to the RSM results, all the independent parameters are equally
      important in dye removal efficiency. In addition, ANFIS was applied for dye
      removal efficiency and operating costs modeling. High R(2) values (>=85%)
      indicate that the predictions of RSM and ANFIS models are acceptable for both
      responses. ANFIS was also used in MOPSO for finding the best techno-economical
      Reactive Blue 19 elimination conditions according to RSM design. Through MOPSO
      and the selected ANFIS model, Minimum and maximum values of 58.27% and 99.67% dye
      removal efficiencies were obtained, respectively. 

PMID- 23867838
TI  - Comparative study of ageing, heat treatment and accelerated carbonation for
      stabilization of municipal solid waste incineration bottom ash in view of
      reducing regulated heavy metal/metalloid leaching.
AB  - This study compared the performance of four different approaches for
      stabilization of regulated heavy metal and metalloid leaching from municipal
      solid waste incineration bottom ash (MSWI-BA): (i) short term (three months) heap
      ageing, (ii) heat treatment, (iii) accelerated moist carbonation, and (iv)
      accelerated pressurized slurry carbonation. Two distinct types of MSWI-BA were
      tested in this study: one originating from a moving-grate furnace incineration
      operation treating exclusively household refuse (sample B), and another
      originating from a fluid-bed furnace incineration operation that treats a mixture
      of household and light industrial wastes (sample F). The most abundant elements
      in the ashes were Si (20-27 wt.%) and Ca (16-19 wt.%), followed by significant
      quantities of Fe, Al, Na, S, K, Mg, Ti, and Cl. The main crystalline substances
      present in the fresh ashes were Quartz, Calcite, Apatite, Anhydrite and
      Gehlenite, while the amorphous fraction ranged from 56 to 73 wt.%. The leaching
      values of all samples were compared to the Flemish (NEN 7343) and the Walloon
      (DIN 38414) regulations from Belgium. Batch leaching of the fresh ashes at
      natural pH showed that seven elements exceeded at least one regulatory limit (Ba,
      Cr, Cu, Mo, Pb, Se and Zn), and that both ashes had excess basicity (pH > 12).
      Accelerated carbonation achieved significant reduction in ash basicity (9.3-9.9);
      lower than ageing (10.5-12.2) and heat treatment (11.1-12.1). For sample B, there
      was little distinction between the leaching results of ageing and accelerated
      carbonation with respect to regulatory limits; however carbonation achieved
      comparatively lower leaching levels. Heat treatment was especially detrimental to
      the leaching of Cr. For sample F, ageing was ineffective and heat treatment had
      marginally better results, while accelerated carbonation delivered the most
      effective performance, with slurry carbonation meeting all DIN limits. Slurry
      carbonation was deemed the most effective treatment process, achieving
      consistently significant leaching stabilization, while also effectively washing
      out Cl ions, a requirement for the utilization of the ashes in construction
      applications. The benefits of carbonation were linked to the formation of
      significant quantities of Ca-carbonates, including appreciable quantities of the
      Aragonite polymorph formed in the slurry carbonated samples. 

PMID- 23867839
TI  - Chromium removal using resin supported nanoscale zero-valent iron.
AB  - Resin supported nanoscale zero-valent iron (R-nZVI) was synthesized by the
      borohydride reduction method. Batch experiments were conducted to evaluate the
      factors affecting Cr(VI) removal. It was found that nZVI loads, resin dose, pH
      value and initial concentration of Cr(VI) were all important factors. Scanning
      electron microscopy showed that the nZVI particles in R-nZVI became sphere after
      reacting with Cr(VI). This phenomenon was attributed to the co-precipitation of
      Cr(III) and Fe(III) on the surface of resin. X-ray diffraction pattern confirmed
      that Fe(0) diminished after the reaction. At optimum conditions, the Cr(VI)
      removal efficiency was 84.4% when the initial concentration of Cr(VI) was 20.0
      mg/L. Regeneration of R-nZVI and resin was possible. R-nZVI can also remove
      Cr(III) efficiently. However, the removal mechanisms of Cr(VI) (anion) and
      Cr(III) (cation) are different. The former is chemical reduction, while the
      latter is ion exchange at pH below 6.3 and precipitation at pH above 6.3. This
      study demonstrates that R-nZVI has the potential to become an effective agent for
      treating wastewater containing Cr(VI) and Cr(III). 

PMID- 23867840
TI  - Counteracting the accidental pollutant propagation in a section of the River
      Somes by automatic control.
AB  - Real-time response to accidental pollution in rivers is a challenging mission
      that requires efficient on-line monitoring and rapid mitigating systems and calls
      for automatic control for diminishing or eliminating the pollutant effect.
      Remediation measures are addressed for cases in which the pollutant concentration
      can be measured and a neutralising agent can be identified and added to react
      with the pollutant and transform it by a chemical reaction into less harmful or
      non-harmful products. Pollution in a section of the River Somes is presented as a
      case study. Based on the advection-dispersion-reaction processes, a 2D dynamic
      simulator is developed to investigate and provide accurate predictions of the
      pollutant distribution. The complex river section geometry, the single and
      multiple points or spatially distributed sources, and a constant or time-varying
      release of the pollutant may be handled by the simulator. Furthermore, two
      control systems are designed and tested. One system involves implementing a
      feedback control approach, while the other involves applying a feedforward
      feedback control structure. System identification of the disturbance and the
      manipulated variable paths is carried out, and a suitable allocation of the
      measuring points for both the disturbance and the controlled variable is
      addressed and demonstrated. The control structures prove to help the proposed
      polluting counteracting measures by bringing the concentration of the pollutant
      down to the safe setpoint value. The predictive action of the feedforward
      feedback control structure reveals complementary benefits, as the pollutant
      concentration is promptly forced and maintained below the maximum allowed limit
      all the time and all over the river region of interest. 

PMID- 23867841
TI  - Effect of ramipril on walking times and quality of life among patients with
      peripheral artery disease and intermittent claudication: a randomized controlled
      trial. Journal of the American Medical Association 2013; 309: 453-460.
AB  - STUDY OBJECTIVE: The objective of the trial was to examine whether ramipril, an
      angiotensin-converting enzyme (ACE), improves walking distance and health-related
      quality of life in patients with peripheral artery disease (PAD) associated with
      claudication. STUDY POPULATION: The study enrolled 212 patients with risk factors
      and symptoms of PAD treated by conventional therapies at three centers in
      Australia. All patients had an ankle-brachial index (ABI) of less than 0.90 at
      rest and intermittent claudication in at least one leg, which were stable for at
      least 6 preceding months along with the medication regimen. The patients were
      excluded if blood pressure was not controlled (brachial blood pressure of 160/100
      mmHg or greater); if there was current or recent use of either ACE inhibitors or
      angiotensin II receptor blockers, potassium-sparing diuretics, or potassium
      supplements; renal failure (serum creatinine level 2.3 mg/dL or greater [200
      umol/L]); renal artery stenosis; previous coronary or peripheral artery
      revascularizations, recent myocardial infarction and other health conditions
      other than PAD that could adversely influence walking ability at the time of
      screening and for 1 year thereafter. DESIGN AND METHODS: This was a randomized,
      placebo-controlled, triple blinded study of ramipril at the high daily dose (10
      mg) for 6 months. Primary outcomes were pain-free and maximum walking times
      assessed by a standard treadmill exercise test. Secondary outcomes were ABI
      changes; symptoms and functional status assessed by the Walking Impairment
      Questionnaire (WIQ)(1); health-related quality of life assessed by the Short-Form
      36 Health Survey (SF-36)(2); and stenosis severity assessed by duplex ultrasound
      of the lower limb arteries. At baseline and at follow-up, pain-free and maximum
      walking distances were assessed by the standard constant load treadmill exercise
      test performed at a speed of 3.2 km/h and a grade of 12%.(3) ABI was calculated
      in both legs. Duplex ultrasonography was used to determine stenosis in lower-limb
      vessel segments. Functional changes per WIQ, and perceived disability assessed on
      the Physical Component Summary and the Mental Component Summary of the SF-36 were
      self-reported. Sample size was calculated as 100 patients per each group needed
      to provide a power of 80% at an alpha of 0.05 to detect a 120-second change in
      walking time and a 65-second change in pain-free walking time. A two-sided p
      value of less than 0.05 was considered significant. Baseline variables were
      compared using the chi(2) test and one-way analysis of variance. The analysis of
      covariance model with baseline and post-treatment values after 6 months used
      Kruskal-Wallis analysis of variance. Imputations for missing 6-month data were
      performed. Data were analyzed on the intention-to-treat basis. RESULTS: Of 921
      potential participants screened, 212 eligible participants were randomized into
      equal-sized ramipril and placebo groups where baseline parameters were not
      different. Compliance was monitored by pill count and adverse effects were
      monitored through interval clinical assessments, laboratory tests, and telephone
      calls. There was a 100% adherence rate to the study medications among 200
      patients who completed the study. Ramipril was associated with a 75-second
      increase in mean pain-free and a 255-second increase in maximum walking time.
      There was a modest (less than 5 mmHg) blood pressure reduction and a small (0.1)
      ABI increase at rest and after exercise compared to placebo. The maximum walking
      time increase after ramipril therapy compared to placebo was greater in the
      subgroup of patients with femoropopliteal disease (286 seconds) than in those
      with aortoiliac disease (127 seconds). Patients treated with ramipril showed
      improvement of the median distance, speed and stair climbing scores on the WIQ,
      as well as of the Physical, but not the Mental, Component Summary score on the SF
      36. The most frequent side effect was dizziness, more common in the ramipril
      (8.5%) than in the placebo (2.8%) group. Persistent cough occurred in 6.6% of
      patients on ramipril, causing their withdrawal from the study.

PMID- 23867842
TI  - Structural composition of myocardial infarction scar in middle-aged male and
      female rats: does sex matter?
AB  - The present study was designed to determine whether the structural composition of
      the scar in middle-aged post-myocardial infraction (MI) rats is affected by the
      biological sex of the animals. A large MI was induced in 12-month-old male (M-MI)
      and female (F-MI) Sprague-Dawley rats by ligation of the left coronary artery.
      Four weeks after the MI, rats with transmural infarctions, greater than 50% of
      the left ventricular (LV) free wall, were evaluated. The extent of LV remodeling
      and fractional volumes of fibrillar collagen (FC), myofibroblasts, vascular
      smooth muscle (SM) cells, and surviving cardiac myocytes (CM) in the scars were
      compared between the two sexes. The left ventricle of post-MI male and female
      rats underwent a similar degree of remodeling as evidenced by the analogous scar
      thinning ratio (0.46 +/- 0.02 vs. 0.42 +/- 0.05) and infarct expansion index
      (1.06 +/- 0.07 vs. 1.12 +/- 0.08), respectively. Most important, the contents of
      major structural components of the scar revealed no evident difference between M
      MI and F-MI rats (interstitial FC, 80.74 +/- 2.08 vs. 82.57 +/- 4.53;
      myofibroblasts, 9.59 +/- 1.68 vs.9.56 +/- 1.15; vascular SM cells, 2.27 +/- 0.51
      vs. 3.38 +/- 0.47; and surviving CM, 3.26 +/- 0.39 vs. 3.05 +/- 0.38,
      respectively). Our data are the first to demonstrate that biological sex does not
      influence the structural composition of a mature scar in middle-aged post-MI
      rats. 

PMID- 23867844
TI  - Altered thermal sensitivity in facial skin in chronic whiplash-associated
      disorders.
AB  - There is a close functional relationship between the jaw and neck regions and it
      has been suggested that trigeminal sensory impairment can follow whiplash injury.
      Inclusion of manageable routines for valid assessment of the facial sensory
      capacity is thus needed for comprehensive evaluations of patients exposed to such
      trauma. The present study investigated facial thermal thresholds in patients with
      chronic whiplash-associated disorders (WADs) with both a qualitative method and
      quantitative sensory testing (QST). Ten women with pain and dysfunction following
      a whiplash injury were compared to 10 healthy age-matched women. Thermal
      detection thresholds were assessed by qualitative chair-side testing and by QST
      according to the method-of-limits. Seven test sites in the facial skin (overlying
      each trigeminal branch bilaterally, and the midpoint of the chin) were examined.
      The detection warm and cold thresholds were defined as the mean values of 10
      individual thresholds. For the WAD patients, the qualitative assessment
      demonstrated both reduced and increased sensitivity compared to the healthy,
      whereas QST systematically showed significantly higher detection thresholds
      (i.e., decreased sensitivity) for both cold and warm stimuli. For the individuals
      who were assessed as having increased sensitivity in the qualitative assessment,
      the QST displayed either normal or higher thresholds, i.e., decreased
      sensitivity. The results suggest that QST is more sensitive for detecting thermal
      sensory disturbances in the face than a qualitative method. The impaired thermal
      sensitivity among the patients corroborates the notion of altered thermal
      detection capacity induced by WAD-related pain. 

PMID- 23867843
TI  - Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce
      ultrastructural damage, and alter bacterial lipid and protein compositions.
AB  - Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a
      variety of Gram-positive and Gram-negative bacteria; however, little is known
      about their spectrum of antimicrobial activity or mechanisms of action against
      oral bacteria. In this study, we examine the activity of two fatty acids and
      three sphingoid bases against Porphyromonas gingivalis, an important colonizer of
      the oral cavity implicated in periodontitis. Minimal inhibitory concentrations,
      minimal bactericidal concentrations, and kill kinetics revealed variable, but
      potent, activity of oral mucosal and salivary lipids against P. gingivalis,
      indicating that lipid structure may be an important determinant in lipid
      mechanisms of activity against bacteria, although specific components of
      bacterial membranes are also likely important. Electron micrographs showed
      ultrastructural damage induced by sapienic acid and phytosphingosine and
      confirmed disruption of the bacterial plasma membrane. This information, coupled
      with the association of treatment lipids with P. gingivalis lipids revealed via
      thin layer chromatography, suggests that the plasma membrane is a likely target
      of lipid antibacterial activity. Utilizing a combination of two-dimensional in
      gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus
      degradation sequencing we also show that treatment with sapienic acid induces
      upregulation of a set of proteins comprising a unique P. gingivalis stress
      response, including proteins important in fatty acid biosynthesis, metabolism and
      energy production, protein processing, cell adhesion and virulence. Prophylactic
      or therapeutic lipid treatments may be beneficial for intervention of infection
      by supplementing the natural immune function of endogenous lipids on mucosal
      surfaces. 

PMID- 23867846
TI  - Uncertainty in biogenic isoprene emissions and its impacts on tropospheric
      chemistry in East Asia.
AB  - In this study, the accuracy of biogenic isoprene emission fluxes over East Asia
      during two summer months (July and August) was examined by comparing two
      tropospheric HCHO columns (OmegaHCHO) obtained from the SCIAMACHY sensor and the
      Community Multi-scale Air Quality (CMAQ v4.7.1) model simulations, using three
      available biogenic isoprene emission inventories over East Asia: i) GEIA, ii)
      MEGAN and iii) MOHYCAN. From this comparative analysis, the tropospheric HCHO
      columns from the CMAQ model simulations, using the MEGAN and MOHYCAN emission
      inventories (Omega(CMAQ, MEGAN) and Omega(CMAQ, MOHYCAN)), were found to agree
      well with the tropospheric HCHO columns from the SCIAMACHY observations
      (Omega(SCIA)). Secondly, the propagation of such uncertainties in the biogenic
      isoprene emission fluxes to the levels of atmospheric oxidants (e.g., OH and HO2)
      and other atmospheric gaseous/particulate species over East Asia during the two
      summer months was also investigated. As the biogenic isoprene emission fluxes
      decreased from the GEIA to the MEGAN emission inventories, the levels of OH
      radicals increased by factors of 1.39 and 1.75 over Central East China (CEC) and
      South China, respectively. Such increases in the OH radical mixing ratios
      subsequently influence the partitioning of HO(y) species. For example, the HO2/OH
      ratios from the CMAQ model simulations with GEIA isoprene emissions were 2.7
      times larger than those from the CMAQ model simulations based on MEGAN isoprene
      emissions. The large HO2/OH ratios from the CMAQ model simulations with the GEIA
      biogenic emission were possibly due to the overestimation of GEIA biogenic
      isoprene emissions over East Asia. It was also shown that such large changes in
      HO(x) radicals created large differences on other tropospheric compounds (e.g.,
      NO(y) chemistry) over East Asia during the summer months.

PMID- 23867845
TI  - Heparinized collagen scaffolds with and without growth factors for the repair of
      diaphragmatic hernia: construction and in vivo evaluation.
AB  - A regenerative medicine approach to restore the morphology and function of the
      diaphragm in congenital diaphragmatic hernia is especially challenging because of
      the position and flat nature of this organ, allowing cell ingrowth primarily from
      the perimeter. Use of porous collagen scaffolds for the closure of surgically
      created diaphragmatic defects in rats has been shown feasible, but better
      ingrowth of cells, specifically blood vessels and muscle cells, is warranted. To
      stimulate this process, heparin, a glycosaminoglycan involved in growth factor
      binding, was covalently bound to porous collagenous scaffolds (14%), with or
      without vascular endothelial growth factor (VEGF; 0.4 ug/mg scaffold), hepatocyte
      growth factor (HGF; 0.5 ug/mg scaffold) or a combination of VEGF + HGF (0.2 + 0.5
      ug/mg scaffold). All components were located primarily at the outside of
      scaffolds. Scaffolds were implanted in the diaphragm of rats and evaluated after
      2 and 12 weeks. No herniations or eventrations were observed, and in several
      cases, growth factor-substituted scaffolds showed macroscopically visible blood
      vessels at the lung site. The addition of heparin led to an accelerated ingrowth
      of blood vessels at 2 weeks. In all scaffold types, giant cells and immune cells
      were present primarily at the liver side of the scaffold, and immune cells and
      individual macrophages at the lung side; these cell types decreased in number
      from week 2 to week 12. The addition of growth factors did not influence cellular
      response to the scaffolds, indicating that further optimization with respect to
      dosage and release profile is needed. 

PMID- 23867848
TI  - A comparison of fractal methods and probability plots in identifying and mapping
      soil metal contamination near an active mining area, Iran.
AB  - Mining activities may contribute significant amounts of metals to surrounding
      soils. Assessing the potential effects and extent of metal contamination requires
      the differentiation between geogenic and additional anthropogenic sources. This
      study compares the use of conventional probability plots with two forms of
      fractal analysis (number-size and concentration-area) to separate geochemical
      populations of ore-related elements in agricultural area soils adjacent to Pb-Zn
      mining operations in the Irankuh Mountains, central Iran. The two general
      approaches deliver similar spatial groupings of univariate geochemical
      populations, but the fractal methods provide more distinct separation between
      populations and require less data manipulation and modeling than the probability
      plots. The concentration-area fractal approach was more effective than the number
      size fractal and probability plotting methods at separating sub-populations
      within the samples affected by contamination from the mining operations. There is
      a general lack of association between major elements and ore-related metals in
      the soils. The background populations display higher relative variation in the
      major elements than the ore-related metals whereas near the mining operations
      there is far greater relative variation in the ore-related metals. The extent of
      the transport of contaminants away from the mine site is partly a function of the
      greater dispersion of Zn compared with Pb and As, however, the patterns indicate
      dispersion of contaminants from the mine site is via dust and not
      surface/groundwater. A combination of geochemical and graphical assessment, with
      different methods of threshold determination, is shown to be effective in
      separating geogenic and anthropogenic geochemical patterns. 

PMID- 23867847
TI  - Essential and toxic element concentrations in blood and urine and their
      associations with diet: results from a Norwegian population study including high
      consumers of seafood and game.
AB  - The first aim of the study was to evaluate calculated dietary intake and
      concentrations measured in blood or urine of essential and toxic elements in
      relation to nutritional and toxicological reference values. The second aim was to
      identify patterns of the element concentrations in blood and urine and to
      identify possible dietary determinants of the concentrations of these elements.
      Adults with a known high consumption of environmental contaminants (n=111), and a
      random sample of controls (n=76) answered a validated food frequency
      questionnaire (FFQ). Complete data on biological measures were available for 179
      individuals. Blood and urine samples were analyzed for selenium, iodine, arsenic,
      mercury, cadmium and lead. Principal component analysis was used to identify
      underlying patterns of correlated blood and urine concentrations. The calculated
      intakes of selenium, iodine, inorganic arsenic and mercury were within guideline
      levels. For cadmium 24% of the high consumer group and 8% of the control group
      had intakes above the tolerable weekly intake. Concentrations of lead in blood
      exceeded the bench-mark dose lower confidence limits for some participants.
      However, overall, the examined exposures did not give rise to nutritional or
      toxicological concerns. Game consumption was associated with lead in blood (B(ln)
      0.021; 95%CI:0.010, 0.031) and wine consumption. Seafood consumption was
      associated with urinary cadmium in non-smokers (B(ln) 0.009; 95%CI:0.003, 0.015).
      A novel finding was a distinct pattern of positively associated biological
      markers, comprising iodine, selenium, arsenic and mercury (eigenvalue 3.8),
      reflecting seafood intake (B 0.007; 95%CI:0.004, 0.010). The study clearly
      demonstrates the significance of seafood as a source of both essential nutrients
      and toxic elements simultaneously and shows that exposure to various essential
      and toxic elements can be intertwined.

PMID- 23867849
TI  - Pla a_1 aeroallergen immunodetection related to the airborne Platanus pollen
      content.
AB  - Platanus hispanica pollen is considered an important source of aeroallergens in
      many Southern European cities. This tree is frequently used in urban green spaces
      as ornamental specie. The flowering period is greatly influenced by the
      meteorological conditions, which directly affect its allergenic load in the
      atmosphere. The purpose of this study is to develop equations to predict the
      Platanus allergy risk periods as a function of the airborne pollen, the allergen
      concentration and the main meteorological parameters. The study was conducted by
      means two volumetric pollen samplers; a Lanzoni VPPS 2000 for the Platanus pollen
      sampling and a Burkard multivial Cyclone Sampler to collect the aeroallergen
      particles (Pla a_1). In addiction the Dot-Blot and the Raman spectroscopy methods
      were used to corroborate the results. The Pla a_1 protein is recorded in the
      atmosphere after the presence of the Platanus pollen, which extend the Platanus
      pollen allergy risk periods. The Platanus pollen and the Pla a 1 allergens
      concentration are associated with statistical significant variations of some
      meteorological variables: in a positive way with the mean and maximum temperature
      whereas the sign of the correlation coefficient is negative with the relative
      humidity. The lineal regression equation elaborated in order to forecast the
      Platanus pollen content in the air explain the 64.5% of variance of the pollen
      presence in the environment, whereas the lineal regression equation elaborated in
      order to forecast the aeroallergen a 54.1% of the Pla a_1 presence variance. The
      combination of pollen count and the allergen quantification must be assessed in
      the epidemiologic study of allergic respiratory diseases to prevent the allergy
      risk periods. 

PMID- 23867850
TI  - Field validation of a new low-cost method for determining occurrence and duration
      of combined sewer overflows.
AB  - Combined sewer overflow (CSO) events produced in combined sewer systems (CSS)
      during wet weather conditions are a threat for the receiving water bodies. The
      large number of CSO structures normally present in a CSS makes that the
      monitoring of the complete CSO network in a simultaneous way would drastically
      increase the investment costs. In this paper, a new methodology is presented
      aiming to characterize the occurrence and duration of CSO events by means of low
      cost temperature sensors. Hence, a large number of CSO structures can be
      simultaneously monitored and the system can be characterized as a whole. The
      method assumes temperature differences between the overflowing mix of wastewater
      and stormwater and the sewer gas phase, so the temperature shift produced during
      a rainfall episode is related to a CSO event occurrence. The method has been
      tested and validated in La Garriga CSS (Spain) where the temperature at 13 CSO
      weirs was monitored for a period of 1 year (57 rainfall episodes). For the whole
      set of CSO events, occurrence and duration were successfully determined in 80% of
      cases. Advantages, limitations and potential applications of the method are
      discussed at the end of the paper.

PMID- 23867851
TI  - Chromosome aberrations, DNA damage, and risk: matrix reloaded.

PMID- 23867852
TI  - The evaluation of long-term effects of ionizing radiation through measurement of
      current sister chromatid exchange (SCE) rates in radiology technologists,
      compared with previous SCE values.
AB  - Ionizing radiation is a strong physical mutagen, causing breakage of
      phosphodiester bonds in DNA at any stage of the mitotic cycle. Analysis of sister
      chromatid exchange (SCE) has come into use as a sensitive DNA-damage indicator.
      We investigated the SCE rates in radiology technologists who are occupationally
      and chronically exposed to ionizing radiation. The study included 39 radiology
      technologists and 35 sex- and age-matched healthy controls. There was a
      statistically significant difference in the SCE frequency between radiology
      technologists and controls (p<0.0001). Additionally, previous SCE data of 10
      radiology technologists were compared with current results regarding radiation
      exposure time. There was statistically significant difference between previous
      and current SCE values (p=0.005). The significant increase in the frequency of
      SCE in radiology technologists emphasizes the importance of radiation-protection
      procedures in order to minimize radiation exposure and avoid possible genotoxic
      effects. Comparison of two studies that measured SCE values of radiology
      technologists after 8 years also suggests that the genotoxic effect is
      reversible. In conclusion, radiation is still an important mutagenic agent
      despite improvements in daily working hours and conditions. 

PMID- 23867853
TI  - Comparison of biological processes induced in HepG2 cells by tert-butyl
      hydroperoxide (t-BHP) and hydroperoxide (H2O2): The influence of carvacrol.
AB  - This paper presents comparisons of biological impacts of the oxidants H2O2 and t
      BHP on human liver cells, and shows modulation of these effects by the phenolic
      compound carvacrol. To understand better how these oxidants exert their effect on
      DNA and on the activity of the enzymes superoxide dismutase (SOD) and glutathione
      peroxidase (GPx), we measured intracellular antioxidant glutathione (iGSH) and
      intracellular reactive oxidative species (iROS). DNA lesions corresponded to
      single-strand DNA breaks, alkali-labile lesions and formamido-pyrimidine-DNA
      glycosylase (FPG)-sensitive sites. Pre-treatment of cells with carvacrol
      substantially decreased the number of H2O2-induced DNA lesions, but the number of
      t-BHP-induced DNA lesions was not reduced. Activities of both SOD and GPx were
      stimulated significantly by carvacrol and were reduced by the combined effect of
      carvacrol and oxidants. H2O2 and t-BHP alone influenced the level of antioxidant
      enzymes differently. While H2O2 did not markedly change the activity of SOD or
      GPx, lower concentrations of t-BHP stimulated activity of SOD and mainly GPx. The
      level of iROS was increased by both oxidants and decreased by carvacrol applied
      either alone or with oxidants. The level of iGSH was not influenced in any of the
      treatments tested. Our results show that although both oxidants induced oxidative
      stress and damaged cellular DNA, their influences on other molecular processes
      were different. The protective effect of carvacrol against DNA-damaging effects
      of H2O2 was unambiguous, but reduction by carvacrol of the DNA-damaging effect of
      t-BHP was not observed. These results suggest that the phenolic compound
      carvacrol contributes to the defence mechanisms of the human organism, but these
      beneficial effects are dependent on the origin and source of the actual oxidative
      stress. 

PMID- 23867854
TI  - Participation of gap junction communication in potentially lethal damage repair
      and DNA damage in human fibroblasts exposed to low- or high-LET radiation.
AB  - Existing research has not fully explained how different types of ionizing
      radiation (IR) modulate the responses of cell populations or tissues. In our
      previous work, we showed that gap junction intercellular communication (GJIC)
      mediates the propagation of stressful effects among irradiated cells exposed to
      high linear energy transfer (LET) radiations, in which almost every cells is
      traversed by an IR track. In the present study, we conducted an in-depth study of
      the role of GJIC in modulating the repair of potentially lethal damage (PLDR) and
      micronuclei formation in cells exposed to low- or high-LET IR. Confluent human
      fibroblasts were exposed in the presence or absence of a gap junction inhibitor
      to 200kV X rays (LET~1.7keV/MUm), carbon ions (LET~76keV/MUm), silicon ions
      (LET~113keV/MUm) or iron ions (LET~400keV/MUm) that resulted in isosurvival
      levels. The fibroblasts were incubated for various times at 37 degrees C. As
      expected, high-LET IR were more effective than were low-LET X rays at killing
      cells and damaging DNA shortly after irradiation. However, when cells were held
      in a confluent state for several hours, PLDR associated with a reduction in DNA
      damage, occurred only in cells exposed to X rays. Interestingly, inhibition of
      GJIC eliminated the enhancement of toxic effects, which resulted in an increase
      of cell survival and reduction in the level of micronucleus formation in cells
      exposed to high, but not in those exposed to low-LET IR. The experiment shows
      that gap-junction communication plays an important role in the propagation of
      stressful effects among irradiated cells exposed to high-LET IR while GJIC has
      only a minimal effect on PLDR and DNA damage following low-LET irradiation.
      Together, our results show that PLDR and induction of DNA damage clearly depend
      on gap-junction communication and radiation quality. 

PMID- 23867855
TI  - A 3' splice site mutation of IDS gene in a Chinese family with
      mucopolysaccharidosis type II.
AB  - The purpose of this study was to identify the underlying genetic cause in a four
      generation Chinese family diagnosed with mucopolysaccharidosis type II.
      Peripheral blood samples were collected from family members and the iduronate-2
      sulfatase (IDS) gene was analyzed by DNA sequencing. The impact of IDS mutations
      on mRNA transcription was determined by quantitative real-time RT-PCR (qRT-PCR)
      in both patients as well as in healthy control samples. In addition, RT-PCR was
      performed to confirm the characteristics of a found mutation located in non
      canonical splicing site. A 3' splice site mutation c.880-8A>G (IVS 6-8A>G) was
      identified in two members of the analyzed MPS II family and sequencing of RT-PCR
      products showed that this mutation activates an upstream cryptic splice-site in
      intron 6, leads to the 7 nucleotide insertion in exon 7, which in turn results in
      an exon 7 frameshift introducing a premature stop codon and shorter peptide
      chain. In addition, qRT-PCR products from the two patients showed a reduced IDS
      mRNA expression (43.9% and 71.2%, respectively), when compared with the average
      IDS mRNA expression in healthy control samples, possibly as a result of nonsense
      mediated mRNA decay. In conclusion, in this study, we have identified an IDS gene
      splice mutation which is associated with clinically attenuated MPS II phenotype.
      In addition, our study accentuates the importance of cDNA analysis in the
      detection of intronic mutations, since in the studies examining only gDNA, the
      link between genotype and phenotype may have been misinterpreted. 

PMID- 23867856
TI  - Potential use of DNA barcoding for the identification of Salvia based on cpDNA
      and nrDNA sequences.
AB  - An effective DNA marker for authenticating the genus Salvia was screened using
      seven DNA regions (rbcL, matK, trnL-F, and psbA-trnH from the chloroplast genome,
      and ITS, ITS1, and ITS2 from the nuclear genome) and three combinations
      (rbcL+matK, psbA-trnH+ITS1, and trnL-F+ITS1). The present study collected 232
      sequences from 27 Salvia species through DNA sequencing and 77 sequences within
      the same taxa from the GenBank. The discriminatory capabilities of these regions
      were evaluated in terms of PCR amplification success, intraspecific and
      interspecific divergence, DNA barcoding gaps, and identification efficiency via a
      tree-based method. ITS1 was superior to the other marker for discriminating
      between species, with an accuracy of 81.48%. The three combinations did not
      increase species discrimination. Finally, we found that ITS1 is a powerful
      barcode for identifying Salvia species, especially Salvia miltiorrhiza.

PMID- 23867857
TI  - Previous open renal surgery increased vascular complications in percutaneous
      nephrolithotomy (PCNL) compared with primary and secondary PCNL and
      extracorporeal shock wave lithotripsy patients: a retrospective study.
AB  - OBJECTIVE: To evaluate the vascular complications of percutaneous nephrolithotomy
      (PCNL) patients who have undergone previous open surgery, PCNL and extracorporeal
      shock wave lithotripsy (ESWL). PATIENTS AND METHODS: 360 patients who underwent a
      PCNL procedure were included into the study. The patients were divided into 4
      groups: group 1: primary PCNL (n = 232); group 2: previous open nephrolithotomy
      (n = 42); group 3: previous PCNL (n = 33); group 4: previous ESWL (n = 63). The
      periods of operation and fluoroscopy use of the groups were compared in terms of
      residual stones, with haematuria, pre-operation and post-operation first-day
      haemoglobin values. Patients with persistent haematuria were assessed through
      ultrasonography (US), Doppler US, computed tomography and angiography. RESULTS:
      Upon comparison of the patients' pre- and post-operative haemoglobin changes,
      haemoglobin was statistically higher in the previous open operation group than
      the others (p = 0.02). Permanent and intermittent haematuria were detected in 12
      (3%) and 7 patients (1%), respectively. Angiography was done in 7 (1.94%)
      patients. This rate was 9.5% for group 2 and 3% for group 3. These rates were
      found to be statistically higher than compared to the other groups. Arteriovenous
      fistula (AVF) was detected in 4 of these patients and pseudoaneurysm in 1. While
      1 of the patients with AVF improved spontaneously, embolisation was applied to 4
      patients. Four of the patients had had a previous open operation, while 1 had had
      a PCNL treatment. CONCLUSIONS: Vascular complication is a rare complication of
      PCNL that can be successfully managed with angioembolisation. Our results
      indicate that previous open surgery significantly predicted the occurrence of
      these lesions.

PMID- 23867858
TI  - A large epidermoid cyst developing in the palm: A case report.
AB  - INTRODUCTION: Epidermoid cysts, also called atheromas, are frequently observed.
      These cysts originate mostly in the pilosebaceous apparatus but rarely in areas
      without hair, such as the palm and sole. The mechanism of their development has
      been reported to be epidermal inclusion secondary to trauma or human
      papillomavirus (HPV)-60 infection. We report the patient who developed an
      epidermoid cyst in the palm without any known cause. PRESENTATION OF CASE: A 93
      year-old male noticed a mass in the left palm 3 years earlier, was diagnosed with
      an epidermoid cyst based on incisional biopsy, and underwent incision drainage
      several times during the 3-year period. However, since the cyst spontaneously
      ruptured and was infected, debridement and resection of the cyst were performed.
      The postoperative course was favorable, without signs of infection. The
      pathological diagnosis of the resected specimen was an epidermoid cyst.
      DISCUSSION: This case was a rare epidermoid cyst originating in an area without
      hair, and there was neither a clear history of injury nor findings strongly
      suggesting HPV-60 infection. Causes other than repeated loading on the palm could
      not be considered for epidermal inclusion. To our knowledge, this case is the
      largest reported epidermoid cyst. CONCLUSION: Epidermoid cysts are frequently
      observed, but their development in areas without hair is rare, and its mechanism
      has not been clarified. The association between this cyst and trauma or HPV is
      clear. However, repeated loading on areas such as the palm that tend to undergo
      chronic loading can also be a cause, as in this patient.

PMID- 23867859
TI  - Treatment options for visceral artery aneurysms: ten year experience.
AB  - AIM: Open surgical repair (OSR) and endovascular techniques (ET) are both
      described in the literature for treating visceral artery aneurysms (VAAs). Aim of
      this study is to report a two-center experience of patients treated for a VAA
      using either OSR or ET, analyzing perioperative outcomes. METHODS: Clinical data
      of 32 VAAs in 32 patients treated between January 2001 and May 2011 were
      retrospectively reviewed and outcomes analyzed. RESULTS: Eighteen patients were
      men (56.3%). Median age was 64 years (range 26-79). Sixteen aneurysms were
      symptomatic: half of them were ruptured causing hemoperitoneum or
      gastrointestinal bleeding. ET were employed in 19 cases (59%) using covered
      stents (7 patients), coil embolization (5), plug placement (1), thrombin
      injection (2) and multiple associated techniques (4). OSR consisted in
      aneurysmectomy with end to end anastomoses (5 patients) or interposition graft
      (1), aneurysm ligation (4), splenectomy (2). One patient died during open surgery
      for hemoperitoneum due to VAA rupture (3%). OSR and ET had similar perioperative
      complication rates (5.2% vs. 15.3%, P=0.76). OSR had a longer in-hospital stay
      than ET (8 vs. 4 days, P=0.04). The presence of pancreatitis and alcohol abuse
      were more frequent in patients who presented with VAAs rupture. Clinical
      presentation with hemoperitoneum or aneurysm rupture were associated with higher
      mortality, regardless of the type of treatment. CONCLUSION: Both OSR and ET
      offered a safe way to treat VAAs in our experience.

PMID- 23867860
TI  - Cross-flow determination by transcranial Doppler predicts clamping ischemia in
      patients undergoing carotid endarterectomy.
AB  - AIM: Aim of the paper was to assess the reliability of preoperative cross-flow
      determination by transcranial Doppler measurement (TCD) to detect clamping
      ischemia in patients undergoing carotid endarterectomy with selective shunting.
      METHODS: Retrospective one-to-one matched-pair analysis of 72 patients undergoing
      carotid endarterectomy with preoperative TCD scanning. Matching criteria were
      gender, degree of contralateral stenosis and the type of stenosis (asymptomatic
      or symptomatic). RESULTS: Patients in need for a secondary shunt insertion had
      significantly less cross-flow in preoperative TCD measurement (N.=14; 38.89%)
      compared to the control group (N.=32; 88.89%: P=0.0001%). The sensitivity of the
      cross-flow determination to predict clamping ischemia was 88.9%, the specificity
      61.1%. The risk of developing a clamping ischemia in the absence of a cross-flow
      was 12 fold higher (OR: 12.6; 95% CI: 3.7-43.3). The existence of circulatory
      impairment of the MCA was associated with the presence of a collateral flow in
      the ACoA (OR 3.21; P=0.0531; likelihood ratio test 0.0481). Other factors like
      renal insufficiency, the degree of stenosis or the stump pressure showed no
      association with a cross-flow of the ACoA in a multivariate model. CONCLUSION:
      TCD scanning is highly reliable to detect cross-flow prior to carotid surgery and
      thus helpful to identify patients at risk for clamping ischemia and need for
      shunting.

PMID- 23867861
TI  - Symptomatic abdominal aortic aneurysm repair: to wait or not to wait.
AB  - BACKGROUND: In patients with a symptomatic abdominal aortic aneurysm (sAAA),
      acute intervention theoretically reduces rupture risk prior to surgery whereas
      delayed intervention provides surgery under optimised conditions. In the present
      study we evaluated differences in 30-day mortality in patients with a sAAA
      operated within 12 hours compared to patients who received treatment after 12
      hours and who were optimized for surgery. METHODS: All patients with a sAAA who
      were treated within one week after presentation were included in the analyses.
      The 30-day mortality rates of patients operated within 12 hours were compared to
      those operated after 12 hours, adjusted for type of operation and for all
      potential confounders. RESULTS: Of the 89 included patients, 37 patients received
      surgery within 12 hours. In patients treated within 12 hours, 30-day mortality
      rate was 6 (16.2%) compared to 3 (5.8%) in patients treated after 12 hours (odds
      ratio 0.316; CI 0.074-1.358). When adjusted for type of operation and other
      confounders, odds ratios were 0.305 (CI 0.066-1.405) and 0.270 (CI 0.015-4.836),
      respectively. CONCLUSIONS: In a substantial amount of patients with an alleged
      symptomatic AAA, delayed surgery with patient optimisation might be justified.
      However, specific criteria in order to select patients that might benefit from
      delayed surgery need further investigation.

PMID- 23867862
TI  - Ligand dependent self-assembly of hydroxido-bridged dicopper units templated by
      sodium ion.
AB  - Crown-ether like interaction of two neutral [Cu2(MU-OH)(MU-L(1))] (H3L(1) = 2-(2'
      hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine)
      fragments, around a central Na(+) cation as self-assembly template, led to the
      formation of [Na{Cu2(MU-OH)(MU-L(1))}2]ClO4 (1). Di-tert-butyl group substituted
      H3L(2) {2-(3,5-di-tert-butyl-2-hydroxyphenyl)-1,3-bis[4-(3,5-di-tert-butyl-2
      hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine} conversely yields only [Cu2(MU
      OH)(MU-L(2))].1.5H2O (2), by discarding aggregation around the Na(+) ion. The
      crown-ether type aggregate 1 exhibits ferromagnetic interactions within the
      double oxido-phenoxido [Cu2] fragments and weak antiferromagnetic interactions
      are mediated by the ONa(+)O bridges. Complex 2 registers only weak
      antiferromagnetic interactions within the oxido-phenoxido bridged [Cu2] entity.
      UV-visible and emission titration spectroscopy establish the interaction of
      cationic complex 1 with calf thymus DNA in Tris buffer and it cleaves supercoiled
      pBR322 DNA from in situ generated ROS. 

PMID- 23867863
TI  - Citizen Science: linking the recent rapid advances of plant flowering in Canada
      with climate variability.
AB  - The timing of crucial events in plant life cycles is shifting in response to
      climate change. We use phenology records from PlantWatch Canada 'Citizen Science'
      networks to study recent rapid shifts of flowering phenology and its relationship
      with climate. The average first flower bloom day of 19 Canadian plant species has
      advanced by about 9 days during 2001-2012. 73% of the rapid and unprecedented
      first bloom day advances are explained by changes in mean annual national
      temperature, allowing the reconstruction of historic flower phenology records
      starting from 1948. The overall trends show that plant flowering in Canada is
      advancing by about 9 days per  degrees C. This analysis reveals the strongest
      biological signal yet of climate warming in Canada. This finding has broad
      implications for niche differentiation among coexisting species, competitive
      interactions between species, and the asynchrony between plants and the organisms
      they interact with. 

PMID- 23867864
TI  - Plasticity in the adult oculomotor system: offline consolidation phase gains in
      saccade sequence learning.
AB  - When do adults gain in learning an oculomotor sequence? Here we show that
      oculomotor training can result not only in performance gains within the training
      session, but also induce robust offline gains in both speed and accuracy.
      Participants were trained and tested over two consecutive days to perform a
      sequence of successive saccades. Saccades were directed to four target letters,
      presented simultaneously at fixed positions. A two alternative-forced choice
      question, after each trial, ensured that all targets were perceived. Eye tracking
      measures were tested at the beginning and end of the training session as well as
      at 24 h post-training. Practice resulted in within-session gains in accuracy and
      a reduction of target fixation duration (although total trial duration remained
      unchanged). In addition, the total average path length traveled by the eye
      increased, reflecting a decrease in undershoot saccades. At 24 h post-training,
      however, additional gains were expressed in both speed and accuracy of
      performance; the total trial duration as well as the fixation-position-offsets
      and the number of corrective saccades decreased. The expression of delayed gains
      indicates offline skill consolidation processes in the eye-movement control
      system. Our results show that the optimization of some aspect, specifically
      saccade speed parameters, of oculomotor sequence performance evolves mainly
      offline, during the post-training consolidation phase, a pattern suggestive of
      learning in an expert system.

PMID- 23867865
TI  - Exome sequencing in familial corticobasal degeneration.
AB  - BACKGROUND: Corticobasal degeneration (CBD) is a neurodegenerative, sporadic
      disorder of unknown cause. Few familial cases have been described. OBJECTIVE: We
      aim to characterize the clinical, imaging, pathological and genetic features of
      two familial cases of CBD. METHODS: We describe two first cousins with CBD
      associated with atypical MRI findings. We performed exome sequencing in both
      subjects and in an unaffected first cousin of similar age. RESULTS: The cases
      include a 79-year-old woman and a 72-year-old man of Native American and British
      origin. The onset of the neurological manifestations was 74 and 68 years
      respectively. Both patients presented with a combination of asymmetric
      parkinsonism, apraxia, myoclonic tremor, cortical sensory syndrome, and gait
      disturbance. The female subject developed left side fixed dystonia. The
      manifestations were unresponsive to high doses of levodopa in both cases.
      Extensive bilateral T1-W hyperintensities and T2-W hypointensities in basal
      ganglia and thalamus were observed in the female patient; whereas these findings
      were more subtle in the male subject. Postmortem examination of both patients was
      consistent with corticobasal degeneration; the female patient had additional
      findings consistent with mild Alzheimer's disease. No Lewy bodies were found in
      either case. Exome sequencing showed mutations leading to possible structural
      changes in MRS2 and ZHX2 genes, which appear to have the same upstream regulator
      miR-4277. CONCLUSIONS: Corticobasal degeneration can have a familial
      presentation; the role of MRS2 and ZHX2 gene products in CBD should be further
      investigated.

PMID- 23867866
TI  - Topographic distribution of cortical thinning in subtypes of multiple system
      atrophy.
AB  - BACKGROUND AND PURPOSE: Despite the predominant degeneration of subcortical
      structures, recent studies have suggested the evidence of cortical involvement in
      multiple system atrophy (MSA). This study aimed to identify the different
      topographic pattern of cortical thinning in MSA according to clinical subtypes,
      and the association of cortical thinning with cerebellar atrophy and other
      disease related metrics. MATERIALS AND METHODS: We used cortical thickness
      analysis in 53 non-demented probable MSA patients (29 with MSA-C, 24 with MSA-P)
      and 35 healthy subjects and modeled local cortical thickness as a linear
      association with cerebellar volume and disease related metrics including age,
      disease duration, cognition and disease severity. RESULTS: We found five clusters
      (left ventromedial prefrontal, bilateral ventrolateral prefrontal cortex, right
      parahippocampal and lingual gyrus) exhibiting significant cortical thinning in
      MSA-C and two clusters (right primary sensory motor and left ventromedial
      prefrontal cortex) exhibiting a thinning tendency in MSA-P compared with the
      control group. In correlation analysis, we identified no cluster exhibiting a
      significant correlation with cerebellar atrophy in both of the MSA groups.
      However, cortical thickness in right parahippocampalgyrus and left ventrolateral
      prefrontal cortex showed significant negative correlation with International
      Cooperative Ataxia Rating Scale subscore of speech disorder in MSA-C group.
      CONCLUSIONS: We identified different topographic distributions of cortical
      thinning in MSA subtypes. Our study suggests that cortical thinning of MSA occurs
      independently of cerebellar atrophy as a primary disease process rather than
      secondary deafferentation.

PMID- 23867867
TI  - Comparative study of diagnostic accuracy of established PCR assays and in-house
      developed sdaA PCR method for detection of Mycobacterium tuberculosis in
      symptomatic patients with pulmonary tuberculosis.
AB  - OBJECTIVES: Indian contribution to global burden of tuberculosis is about 26%. In
      the present study we have developed an in-house PCR assay using primers for sdaA
      gene of Mycobacterium tuberculosis and evaluated against already established
      primers devR, IS6110, MPB64, rpoB primers for diagnosis of pulmonary
      tuberculosis. METHODS: Using universal sample preparation (USP) method, DNA was
      extracted from sputum specimens of 412 symptomatic patients from Delhi, India.
      The DNA so extracted was used as template for PCR amplification using primers
      targeting sdaA, devR, IS6110, MPB64 and rpoB genes. RESULTS: Out of 412, 149
      specimens were considered positive based on composite reference standard (CRS)
      criteria. The in-house designed sdaA PCR showed high specificity (96.5%), the
      high positive likelihood ratio (28), the high sensitivity (95.9%), and the very
      low negative likelihood ratio (0.04) in comparison to CRS. CONCLUSION: Based on
      our results, the sdaA PCR assay can be considered as one of the most reliable
      diagnostic tests in comparison to other PCR based detection methods.

PMID- 23867868
TI  - Tracking axonal action potential propagation on a high-density microelectrode
      array across hundreds of sites.
AB  - Axons are traditionally considered stable transmission cables, but evidence of
      the regulation of action potential propagation demonstrates that axons may have
      more important roles. However, their small diameters render intracellular
      recordings challenging, and low-magnitude extracellular signals are difficult to
      detect and assign. Better experimental access to axonal function would help to
      advance this field. Here we report methods to electrically visualize action
      potential propagation and network topology in cortical neurons grown over custom
      arrays, which contain 11,011 microelectrodes and are fabricated using
      complementary metal oxide semiconductor technology. Any neuron lying on the array
      can be recorded at high spatio-temporal resolution, and simultaneously precisely
      stimulated with little artifact. We find substantial velocity differences
      occurring locally within single axons, suggesting that the temporal control of a
      neuron's output may contribute to neuronal information processing. 

PMID- 23867869
TI  - Is clostridium difficile associated with relapse of inflammatory bowel disease?
      results from a retrospective and prospective cohort study in the Netherlands.
AB  - BACKGROUND: Although Clostridium difficile may be associated with exacerbations
      in inflammatory bowel diseases (IBD), prospective studies identifying the role of
      C. difficile in disease activity are currently lacking. We examined the
      prevalence of C. difficile in feces of (1) symptomatic IBD patients
      retrospectively and (2) consecutive outpatients in relation to disease activity
      prospectively. METHODS: From adult IBD patients with increase of symptoms, fecal
      samples collected between November 2010 and 2011 were tested for C. difficile,
      Salmonella, Shigella, Yersinia, and Campylobacter spp. Within a prospective IBD
      cohort, fecal samples, clinical data, and disease activity scores were collected
      every 3 months and during relapses. Baseline samples from all subjects (170
      Crohn's disease, 116 ulcerative colitis) and additional samples from patients
      with changing disease activity during follow-up (57 Crohn's disease, 31
      ulcerative colitis) were tested for C. difficile and when positive for toxin A
      and B genes by quantitative polymerase chain reaction. RESULTS: From 104
      symptomatic patients, 139 fecal samples were analyzed. Toxinogenic C. difficile
      and Campylobacter jejuni were detected in 3.6% and 1.8%. In the prospective
      cohort, C. difficile prevalence at baseline was significantly different neither
      between ulcerative colitis (3.4%) and Crohn's disease patients (5.9%) nor between
      active (8.2%) and quiescent (3.3%) disease. In multivariable analysis, C.
      difficile was not associated with disease activity, disease subtype, gender,
      antibiotic, and immunosuppressive therapy. Clostridium difficile was also not
      associated with disease activity within patients with changing disease activity
      over time (P = 0.45). CONCLUSIONS: We found a low prevalence of C. difficile, and
      our findings indicate that C. difficile is not a common trigger for exacerbations
      of IBD in clinical practice in the Netherlands.

PMID- 23867870
TI  - Antioxidant properties of mesalamine in colitis inhibit phosphoinositide 3-kinase
      signaling in progenitor cells.
AB  - BACKGROUND: Mesalamine, 5-aminosalicylic acid (5-ASA), is a potent antioxidant
      and is known to enhance peroxisome proliferator-activated receptor gamma activity
      in the intestine. Our previous studies suggested reduced Phosphoinositide 3
      Kinase (PI3K)/beta-catenin signaling as a mechanism for 5-ASA chemoprevention in
      chronic ulcerative colitis (CUC). We now hypothesize that 5-ASA mediates changes
      in intestinal epithelial cell (IEC) reactive oxygen species during colitis to
      affect phosphatase and tensin homolog (PTEN), PI3K, and beta-catenin signaling.
      METHODS: Here, we examined effects of 5-ASA on oxidant-induced cell signaling
      pathways in HT-29 cells, IECs from mice, and biopsy tissue from control and CUC
      patients. Samples were selected to control for inflammation between untreated and
      5-ASA-treated CUC patients. RESULTS: Direct evaluation of IEC in H2O2-stimulated
      whole colonic crypts indicated that 5-ASA reduces reactive oxygen species levels
      in lower crypt IECs where long-lived progenitor cells reside. Analysis of
      biopsies from patient samples revealed that 5-ASA increases expression of the
      antioxidant catalase in CUC patients. Also, 5-ASA increased nuclear peroxisome
      proliferator-activated receptor gamma protein and target gene expression. Data
      showed 5-ASA-induced peroxisome proliferator-activated receptor gamma DNA binding
      to the PTEN promoter (chromatin immunoprecipitation) and reduced both
      phosphorylated and oxidized (inactive) PTEN protein levels. Analysis of patient
      samples revealed 5-ASA that also reduced levels of active phosphorylated Akt in
      inflamed colitis tissue. Reduced PI3K/Akt signaling and expression of beta
      catenin target genes in 5-ASA-treated CUC patients additionally suggests enhanced
      PTEN activity as well. CONCLUSIONS: Therefore, 5-ASA reduces CUC-induced reactive
      oxygen species in colonic progenitor cells and enhances PTEN activity, thus
      attenuating PI3K/Akt signaling. These data suggest that the antioxidant
      properties of 5-ASA may be the predominant mechanism for 5-ASA chemoprevention.

PMID- 23867871
TI  - Serum hepcidin in inflammatory bowel diseases: biological and clinical
      significance.
AB  - BACKGROUND: Hepcidin, a peptide produced by hepatocytes, regulates body iron
      homeostasis. Inflammation increases serum hepcidin, and its determination can be
      useful in the differential diagnosis of anemias during inflammatory diseases.
      METHODS: We measured serum hepcidin-25 and hepcidin-20 isoforms in 54 patients
      with inflammatory bowel diseases (IBD) and 54 reference subjects (36 healthy
      controls and 18 anemic patients without inflammation or renal failure). Disease
      activity, blood counts, iron status, and erythropoiesis-related parameters were
      obtained for all study subjects. RESULTS: In IBD hepcidin-25, the peptide
      bioactive isoform correlated positively with C-reactive protein and serum
      ferritin; an inverse correlation was observed with transferrin, the soluble
      transferrin receptor, and the soluble transferrin receptor to Log(ferritin)
      ratio. Similar correlations were found in reference subjects. Patients with
      anemia of inflammation had higher hepcidin-25 levels than those with iron
      deficiency anemia or a combination of iron deficiency anemia and inflammation (P
      = 0.0061). In patients with inflammation and serum ferritin concentration 100 to
      200 ng/mL, hepcidin-25 was low, suggesting that these patients had iron
      deficiency. A serum hepcidin-25 concentration below 2.0 nM differentiated 85% of
      patients with iron deficiency anemia (with or without inflammation) from patients
      with anemia of inflammation. In IBD, hepcidin-20 correlated with both hepcidin-25
      and C-reactive protein. CONCLUSIONS: In IBD, iron stores, inflammation, and iron
      requirement for erythropoiesis influence serum hepcidin-25. Hepcidin-25
      determination can be useful in the differential diagnosis of IBD-associated
      anemias. Serum hepcidin-20 is linked to hepcidin-25, but inflammation has an
      independent regulatory role on its concentration, indicating that hepcidin-20 may
      have a biological function.

PMID- 23867872
TI  - Video capsule endoscopy impacts decision making in pediatric IBD: a single
      tertiary care center experience.
AB  - BACKGROUND: Little is known about the impact of video capsule endoscopy (VCE) on
      decision making in pediatric patients with IBD. Moreover, few studies have
      reported on the outcomes of treatment changes made based on VCE findings. Our aim
      was to identify the added value of VCE in pediatric patients in a tertiary IBD
      center with established or suspected IBD, by assessing changes in treatments and
      outcomes before and after VCE. METHODS: A retrospective chart review was
      performed in children with established (n = 66) or suspected (n = 17) IBD who
      underwent VCE. Diagnostic classifications, treatments, and clinical outcomes
      before and 1 year after VCE were compared. RESULTS: Primary indications for VCE
      included patients treated for Crohn's disease (CD) with poor growth or active
      symptoms (60%), patients with ulcerative colitis/IBD-unclassified (19%), and
      suspected IBD (20%). Abnormal VCE was seen in 86% of patients with CD, of whom
      75% underwent treatment escalation. One year after VCE, patients with CD improved
      in growth (mean z-scores at baseline and 12 months, -0.5 and 0.2, respectively; P
      < 0.0001), mean body mass index (18.3 and 19.8, respectively; P = 0.004), mean
      erythrocyte sedimentation rate (25 versus 16, respectively; P = 0.012), and
      median Harvey-Bradshaw Index (2 and 0, respectively; P = 0.003). VCE revealed
      more extensive disease than concurrent imaging modalities in 43% of the patients
      with CD. VCE "ruled out" IBD in 94% who had suspected IBD, whereas 50% with
      presumed ulcerative colitis/IBD-unclassified had a diagnosis changed to CD.
      CONCLUSIONS: VCE provides additional clinical information that impacted
      management of pediatric patients with IBD in a tertiary IBD center and was
      associated with improved outcomes.

PMID- 23867873
TI  - Analysis of volatile organic compounds of bacterial origin in chronic
      gastrointestinal diseases.
AB  - BACKGROUND: The aim of this study was to determine whether volatile organic
      compounds (VOCs) present in the headspace of feces could be used to diagnose or
      distinguish between chronic diseases of the gastrointestinal tract and apparently
      healthy volunteers. METHODS: A total of 87 people were recruited, divided between
      4 categories: healthy volunteers (n = 19), Crohn's disease (n = 22), ulcerative
      colitis (n = 20), and irritable bowel syndrome (n = 26). They each supplied fecal
      samples before, and except for the healthy volunteers, after treatment. Fecal
      samples were incubated in a sample bag with added purified air at 40 degrees C
      and headspace samples were taken and concentrated on thermal sorption tubes. Gas
      chromatography-mass spectrometry then desorbed and analyzed these. The
      concentrations of a selection of high-abundance compounds were determined and
      assessed for differences in concentration between the groups. RESULTS: Crohn's
      disease samples showed significant elevations in the concentrations of ester and
      alcohol derivates of short-chain fatty acids and indole compared with the other
      groups; indole and phenol were elevated in ulcerative colitis and irritable bowel
      syndrome but not at a statistically significant level. After treatment, the
      levels of many of the VOCs were significantly reduced and were more similar to
      those concentrations in healthy controls. CONCLUSIONS: The abundance of a number
      of VOCs in feces differs markedly between Crohn's disease and other
      gastrointestinal conditions. Following treatment, the VOC profile is altered to
      more closely resemble that of healthy volunteers.

PMID- 23867876
TI  - Magical NiTi expander.
AB  - A 24-year-old male patient was referred to our department for expansion of the
      constricted maxillary arch as a presurgical procedure for the correction of
      congenital facial disfigurement. On examination, the patient had a convex
      profile, increased interlabial gap, tongue thrust, limited mouth opening,
      posterior crossbite, asymmetric 'V'-shaped maxillary arch with severe
      constriction, crowding of anterior teeth in the maxillary arch and a massive open
      bite. Radiographic investigations included orthopantomograph and occlusal
      radiographs. The patient photographs and models were analysed. On careful
      evaluation, the treatment for maxillary arch expansion was planned with a nickel
      titanium (NiTi) slow maxillary expander along with fixed mechanotherapy for
      alignment of teeth. An unexpectedly successful outcome was appreciated from the
      treatment. An emphasis should be laid on selecting and treating the case of
      constricted arches with a surgical or non-surgical approach, as expansion can be
      achieved orthodontically by using NiTi expanders. 

PMID- 23867875
TI  - Methylated eyes absent 4 (EYA4) gene promotor in non-neoplastic mucosa of
      ulcerative colitis patients with colorectal cancer: evidence for a field effect.
AB  - BACKGROUND: Aberrant methylation of the EYA4 gene (mEYA4) highly discriminates
      ulcerative colitis (UC) cases with colorectal neoplasia from UC controls in both
      tissue and stool. It is not known if mEYA4 is also present in nonadjacent non
      neoplastic mucosa (NNM) of UC patients with colorectal neoplasia. METHODS:
      Formalin-fixed tissues from 25 UC cases with colorectal cancer (CRC) and 25 UC
      controls with neither CRC nor dysplasia were matched on gender, age, disease
      duration, disease extent, and coexistence of primary sclerosing cholangitis. DNA
      was extracted from sections of CRC and NNM from cases and UC control mucosae.
      Bisulfite-treated DNA was amplified using real-time methylation-specific PCR. The
      Wilcoxon rank-sum test assessed differences in mEYA4 levels from CRC, NNM, and
      control samples. Logistic regression was used to estimate sensitivity and
      specificity. RESULTS: Sufficient DNA was available for 20 cases and 20 controls.
      The median mEYA4 level (with interquartile range) was 2 (0-5.7) in control
      mucosae but 93 (38.5-306) in CRC (P < 0.0001) and 27.4 (3-140) in NNM (P =
      0.0009). At 95% specificity, mEYA4 was present in 80% of CRC and 50% of NNM
      tissue samples. The odds ratio of mEYA4 in NNM as an indicator of synchronous CRC
      was 19 (95% confidence interval, 2-170). CONCLUSIONS: The authors demonstrate
      significantly higher mEYA4 levels in NNM and synchronous CRC from UC cases than
      in colorectal mucosae of UC controls without neoplasia. The finding of this CRC
      associated field change has important implications to the use of mEYA4 as a
      potential UC surveillance marker in tissue or stool.

PMID- 23867874
TI  - Balancing and communicating the risks and benefits of biologics in pediatric
      inflammatory bowel disease.
AB  - : Anti-tumor necrosis factor agents are now considered to be a vital component of
      the treatment algorithm for pediatric inflammatory bowel disease. Despite the
      clear benefit of these agents and the realignment of treatment goals to achieve
      early mucosal healing, the decision to initiate therapy is often delayed due to
      uncertainties regarding risks and benefits. The purpose of this review was to
      summarize the currently available data regarding anti-tumor necrosis factor
      agents in pediatric inflammatory bowel disease. Specifically, we review their
      expected efficacy in both Crohn's disease and ulcerative colitis and the
      likelihood of side effects associated with these agents. In addition, we address
      the barriers physicians face when communicating these data and help to identify
      how pediatric patients and their parents can be more involved in a shared
      decision-making process. Through the creation of a new decision aid (Option
      Grid), we hope to allow for a more clear line of communication at the bedside
      when helping patients and parents make these difficult treatment decisions. 

PMID- 23867877
TI  - Reversible retinopathy associated with oral deferasirox therapy.
AB  - A 17-year-old girl with a history of sickle cell anaemia undergoing chronic blood
      transfusions and iron-chelation therapy presented for multiple ophthalmic
      examinations. During treatment with deferoxamine, her examination remained stable
      but 2 years after changing to deferasirox she presented with decreased visual
      acuity and only mild funduscopic changes. Marked electrophysiological
      abnormalities were also evident. After cessation of deferasirox, her visual
      acuity improved and electrophysiological responses improved. No prior reports of
      deferasirox-related retinopathy are available. We suggest that oral deferasirox
      caused a reversible retinopathy in our patient and clinicians be aware of this
      entity. 

PMID- 23867878
TI  - Intravitreal ranibizumab in choroidal neovascularisation due to multifocal
      choroiditis and panuveitis syndrome.
AB  - We report the use of intravitreal ranibizumab as initial and only treatment in a
      case of peripapillary choroidal neovascularisation (CNV) in a patient with
      multifocal choroiditis and panuveitis (MCP) syndrome. A 54-year-old woman
      presented with sudden reduced vision in the right eye of 2 weeks duration. A full
      ophthalmological examination was performed including biomicroscopy, fluorescein
      angiography and optical coherence tomography. A peripapillary choroidal
      neovascular membrane with subretinal haemorrhage extending to the fovea was
      revealed due to MCP syndrome. Three intravitreal injections of ranibizumab were
      performed with monthly intervals. There was clearance of the subretinal
      haemorrhage and reduction of the leakage after the first injection. The visual
      acuity improved to 20/20 in 3 months and remained stable at 2-year follow-up
      without angiographical leakage. Intravitreal injections of ranibizumab could be
      tried in cases of CNV due to MCP syndrome with very good response. 

PMID- 23867880
TI  - What is in? Pneumoperitoneum after sexual intercourse.

PMID- 23867879
TI  - Actinomyces naeslundii and Eikenella corrodens as rare causes of liver abscesses.
AB  - A 48-year-old man with an unremarkable medical history was admitted with vague
      conditions of fever, chills, myalgias and malaise. Physical examination was
      remarkable for only scleral icterus. Laboratory evaluation revealed elevated
      aminotransferases, alkaline phosphatase and bilirubin. Imaging demonstrated two
      masses in the right lobe of his liver, which were ultimately drained and cultures
      demonstrated Actinomyces and Eikenella. He continued to have fever on broad
      spectrum antibiotics until catheter drainage of the abscesses was performed. He
      was eventually discharged in improved condition on amoxicillin-clavulanate. His
      aminotransferases, alkaline phosphatase and bilirubin continued to improve and he
      remained afebrile and asymptomatic. A repeat CT 2 months after discharge
      demonstrated resolution of the abscesses. Actinomyces and Eikenella are rare
      causes of liver abscesses and treatment requires drainage and an extended course
      of antibiotics. The polymicrobial character typical of liver abscesses makes
      antibiotic therapy challenging when cultures reveal rare organisms such as
      Actinomyces and Eikenella. 

PMID- 23867881
TI  - Renal arteriovenous malformation: an unusual cause of recurrent haematuria.
AB  - A 54-year-old woman presented with gross painless haematuria. Initial workup
      showed no abnormality except mild hydronephrosis on CT scan. Cystoscopy and
      retrograde pyelography did not find any gross lesion and her urine cytology was
      also negative. She had recurrent haematuria so her CT was reviewed with the
      radiologist with clinical suspicion of arteriovenous malformation (AVM) which was
      suggested by relatively increased contrast density in the hemiazygous vein and
      renal vein in the arterial phase. She underwent angioembiolisation of left renal
      AVM after which her haematuria settled. 

PMID- 23867882
TI  - Epulis fissuratum: consequence of ill-fitting prosthesis.
AB  - A poorly fitted prosthesis can give rise to a plethora of problems like pain,
      discomfort in mastication and speech and epulis fissuratum. Epulis fissuratum
      refers to reactive tissue response to excessive mechanical pressure imparted by
      the poor fit of prosthesis. In this article, we discuss a case of epulis
      fissuratum in a 69-year-old male patient. 

PMID- 23867883
TI  - Back pain in a previously healthy teenager.
AB  - We present the case of a 14-year-old previously healthy boy who presented to his
      general practitioner with back pain and fever after rugby training. He was
      initially treated for suspected discitis but during the course of his admission
      he rapidly deteriorated and developed severe necrotising pneumonia. He was
      intubated, ventilated and transferred to a paediatric intensive care unit. Panton
      Valentine leukocidin Staphylococcus aureus was suspected and subsequently
      identified in blood cultures. 

PMID- 23867884
TI  - An unusual foreign body in the eye.

PMID- 23867885
TI  - The critical role of caregivers in achieving patient-centered care.

PMID- 23867886
TI  - Coculture of embryonic ventricular myocytes and mouse embryonic stem cell enhance
      intercellular signaling by upregulation of connexin43.
AB  - BACKGROUND: Stem cell therapy has been proposed as a potential treatment strategy
      for ischemic cardiomyopathy in recent years. A variety of stem cells or stem cell
      derived cells can potentially be used for transplantation. Despite improved
      cardiac function after treatment, one of the major problems is the poor
      integration between host and donor cells which can lead to post-transplantation
      arrhythmia and poor long-term outcome. METHODS: In the present study, we
      cocultured murine embryonic stem cells (mES) with murine embryonic ventricular
      myocytes (mEVs) in hanging drops to assess the cellular interaction and function
      of mES-derived cardiomyocytes under these conditions. RESULTS: We found that when
      mEVs are added to a culture system of embryonic stem cells, the number of
      spontaneously beating areas in embryoid bodies (EBs) increases, intercellular gap
      junction communication is enhanced by upregulation of Cx43 expression at the mid
      developmental stage and Cx43 is distributed more orderly between cardiomyocytes.
      CONCLUSIONS: Our findings suggest mES-derived cardiomyocytes are able to form
      effective signaling pathways through coculture with mEVs which is important for
      providing more functional grafts for cardiac cell therapy by improving the
      integration between transplanted and host cells.

PMID- 23867887
TI  - Family satisfaction, pain, and quality-of-life in emerging adults with spina
      bifida: a longitudinal analysis.
AB  - OBJECTIVE: This study uses the Life Course Model for Spina Bifida (SB) to advance
      knowledge of factors associated with change in quality-of-life (QOL) among
      emerging adults with SB. DESIGN: Forty-eight participants (mean [SD], 22.04
      [2.16] yrs) completed self-report questionnaires at two time points, 15 mos
      apart. Four QOL domains (physical health, psychological, social relationships,
      and environment) were measured using the World Health Organization QOL-BREF
      version. SB clinical data were collected via chart reviews. Paired t tests and
      reliable change indices evaluated group- and individual-level QOL change,
      respectively. Multiple regression analyses tested the contributions of the Life
      Course variables in explaining change in QOL over time. RESULTS: No significant
      group-level differences in the QOL domains were found between time 1 and time 2,
      but there was substantial individual variation in QOL over time. SB severity was
      related to a decline only in psychological QOL (B = -0.68, P = 0.02). Increased
      pain was associated with reduced physical health (B = -0.29, P = 0.049) and
      psychological (B = -0.29, P = 0.03) QOL at time 2, whereas greater family
      satisfaction was related to improved QOL in several domains. CONCLUSIONS:
      Clinicians should be aware of the negative impact of pain and the protective
      influence of family satisfaction on QOL in emerging adults with SB.

PMID- 23867888
TI  - Contralaterally controlled neuromuscular electrical stimulation for recovery of
      ankle dorsiflexion: a pilot randomized controlled trial in patients with chronic
      post-stroke hemiplegia.
AB  - OBJECTIVE: The aim of this study was to compare the effects of contralaterally
      controlled neuromuscular electrical stimulation (CCNMES) vs. cyclic neuromuscular
      electrical stimulation (NMES) on lower extremity impairment, functional
      ambulation, and gait characteristics. DESIGN: Twenty-six survivors of stroke with
      chronic (>=6 mos) foot drop during ambulation were randomly assigned to 6 wks of
      CCNMES or cyclic NMES. Both groups had ten sessions per week of self-administered
      home application of either CCNMES or cyclic NMES plus two sessions per week of
      gait training with a physical therapist. Primary outcomes included lower
      extremity Fugl-Meyer score, modified Emory Functional Ambulation Profile, and
      gait velocity. Assessments were made at pretreatment and posttreatment and at 1
      and 3 mos after treatment. RESULTS: There were no significant differences between
      the groups in the outcome trajectories for any of the measures. With data from
      both groups pooled, there were significant but modest and sustained improvements
      in the Fugl-Meyer score and the modified Emory Functional Ambulation Profile but
      not in gait velocity. CONCLUSIONS: The results support the hypothesis that gait
      training combined with either CCNMES or cyclic NMES reduces lower extremity
      impairment and functional ambulation but do not support the hypothesis that
      CCNMES is more effective than cyclic NMES in patients with chronic post-stroke
      hemiplegia.

PMID- 23867889
TI  - [Update on implant allergies].

PMID- 23867890
TI  - [Use of allergy implants in Germany: results of a survey].
AB  - In a representative survey among members of the working group for joint
      replacement (AE) in Germany (86.7% response) it was found that 0.6% of patients
      with total knee arthroplasty (TKA) and 1.2% of patients with total hip
      arthroplasty (THA) may have a problem due to hypersensitivity to nickel or cobalt
      after implantation. Only one third of them may need revision surgery. Although
      patients with hypersensitivity are rare 84% of surgeons would prefer to use a
      specially coated allergy implant for knee arthroplasty patients. However, no long
      term results and few data on the topic of allergies and joint arthroplasty are
      available for these implants so that this has to be critically discussed with
      patients. Before a revision is performed it is recommended to perform knee
      arthroscopy to obtain tissue for microbiological and histopathological
      investigations. The second part of this questionnaire will look at the special
      question of how to deal with allergy patients based on constructed case examples.

PMID- 23867891
TI  - [Histopathological differential diagnostics in context of joint implant allergic
      reactions].
AB  - Total joint replacement has greatly increased over the last decades and so have
      endoprothesis-associated pathologies. European studies have shown a 10-year
      durability varying from 88% to 95%. By means of histopathology different
      pathogenetic synovial-like interface membrane (SLIM) patterns that lead to
      reduction of implant durability can be discerned, such as periprosthetic
      particles, bacterial infections and arthrofibrosis. Subsequently, SLIM types have
      been determined in a revised consensus classification including particle-induced
      type (type I) so-called non-septic loosening, infection type (type II) so-called
      septic loosening, combination type (type III) of bacterial and particle-induced
      types, indifferent type with mechanical and functional disorders (type IV),
      osseus pathologies (type V), arthrofibrotic type (type VI, endoprosthesis
      associated arthrofibrosis) and allergic/immunological/toxic reactions to
      prosthesis material (type VII). Particles are characterized histopathologically
      according to the Krenn particle algorithm. In cases of severe
      lymphocyte/macrophage infiltration, necrosis, abrasion particle detection and
      granuloma formation, a toxic or allergic reaction to implant material should be
      considered. As a direct abrasion particle-induced toxicity cannot be
      differentiated from a particle-induced allergic type VII reaction to implant
      material, the histopathological diagnosis of toxic reaction to implant material
      or allergic reaction to implant material should be made with caution and only in
      association with immunological, allergic and clinical data. It is recommended
      that tissue samples should be arthroscopically taken from different regions:
      close to the prosthesis, distant from the prosthesis and from bone tissue. The
      pathologist should be given information concerning clinical, allergological and
      microbiological data.

PMID- 23867892
TI  - [Posttraumatic complications after pediatric ankle injuries].
AB  - Ankle sprains are common injuries in childhood and are generally harmless.
      However, fractures of the ankle joint are rare, but complications (persistent
      rotational or axial deformity, alteration of growth of the distal tibia or
      fibula, or joint deformity) can lead to serious problems during growth. The
      clinical relevance of growth disturbances at the distal tibia or fibula depends
      on the age at the time of fracture more than on the fracture type, severity of
      dislocation, or interponated material in the fracture gap. Both stimulation and
      inhibition of growth are possible. Inhibition of growth at the distal tibial
      growth plate regularly leads to varus deformity and shortening. This is of
      clinical importance as this type of growth disturbance is the most common. Valgus
      deformity is rare, mostly due to persistent axial deviation of an insufficiently
      reduced fracture. Transitional fractures always occur at the time of growth plate
      closure; thus, growth disturbances do not play a role. Transitional fractures
      could be overlooked or treated insufficiently, leading to a step or gap of the
      joint surface. 

PMID- 23867893
TI  - In response.

PMID- 23867894
TI  - Hyperbaric oxygen reduces matrix metalloproteinases in ischemic wounds through a
      redox-dependent mechanism.
AB  - Little is known about the impact of hyperbaric oxygen treatment (HBOT) on matrix
      metalloproteinase (MMP) production in pre-existing high-oxidant wounds. This
      study aimed to investigate whether HBOT modulates reactive oxygen species (ROS)
      and MMP regulation in ischemic wound tissue. Using a validated ischemic wound
      model, Sprague-Dawley rats were divided into four groups for daily treatment:
      HBOT, N-acetylcysteine (NAC), HBO and NAC, and control (normoxia at sea level).
      High levels of inducible nitric oxide synthase (iNOS), gp91-phox, and 3
      nitrotyrosine were detected in ischemic wounds, indicating high-oxidant stress.
      HBOT not only increased antioxidant enzyme expression, such as Cu/Zn-superoxide
      dismutase, catalase, and glutathione peroxidase, but also significantly decreased
      pro-oxidant enzyme levels, such as iNOS and gp91-phox, thereby decreasing net
      oxygen radical production by means of negative feedback. This effect was blocked
      by NAC treatment in ischemic wounds. HBO-treated ischemic wounds also manifested
      reduced phosphorylation of extracellular signal-regulated kinases 1/2, c-Jun N
      terminal kinase, and c-Jun, indicating downregulation of mitogen-activated
      protein kinases (MAPKs). Furthermore, HBOT decreased the expression of several
      MMPs while simultaneously increasing tissue inhibitor of MMP (tissue inhibitor of
      metalloproteinase 2). These results indicate that HBOT acts via the ROS/MAPK/MMP
      signaling axis to reduce tissue degeneration and improve ischemic wound healing. 

PMID- 23867895
TI  - Mutation in AQP5, encoding aquaporin 5, causes palmoplantar keratoderma Bothnia
      type.

PMID- 23867897
TI  - Atopic dermatitis and disease severity are the main risk factors for food
      sensitization in exclusively breastfed infants.
AB  - Filaggrin (FLG) loss-of-function skin barrier gene mutations are associated with
      atopic dermatitis (AD) and transepidermal water loss (TEWL). We investigated
      whether FLG mutation inheritance, skin barrier impairment, and AD also predispose
      to allergic sensitization to foods. Six hundred and nineteen exclusively
      breastfed infants were recruited at 3 months of age and examined for AD and
      disease severity (SCORing Atopic Dermatitis (SCORAD)), and screened for the
      common FLG mutations. TEWL was measured on unaffected forearm skin. In addition,
      skin prick testing was performed to six study foods (cow's milk, egg, cod, wheat,
      sesame, and peanut). Children with AD were significantly more likely to be
      sensitized (adjusted odds ratio (OR)=6.18, 95% confidence interval (CI): 2.94
      12.98, P<0.001), but this effect was independent of FLG mutation carriage, TEWL,
      and AD phenotype (flexural vs. non-flexural). There was also a strong association
      between food sensitization and AD severity (adjusted ORSCORAD<20=3.91, 95% CI:
      1.70-9.00, P=0.001 vs. adjusted ORSCORAD?20=25.60, 95% CI: 9.03-72.57, P<0.001).
      Equally, there was a positive association between AD and sensitization with
      individual foods (adjusted ORegg=9.48, 95% CI: 3.77-23.83, P<0.001; adjusted
      ORcow's milk=9.11, 95% CI: 2.27-36.59, P=0.002; adjusted ORpeanut=4.09, 95% CI:
      1.00-16.76, P=0.05). AD is the main skin-related risk factor for food
      sensitization in young infants. In exclusively breastfed children, this suggests
      that allergic sensitization to foods can be mediated by cutaneous antigen
      presenting cells. 

PMID- 23867896
TI  - UVB-induced skin inflammation and cutaneous tissue injury is dependent on the MHC
      class I-like protein, CD1d.
AB  - CD1d is a major histocompatibility complex class 1-like molecule that regulates
      the function and development of natural killer T (NKT) cells. Previously, we
      identified a critical role for the CD1d-NKT cell arm of innate immunity in
      promoting the development of UVB-induced p53 mutations, immune suppression, and
      skin tumors. Sunburn, an acute inflammatory response to UVB-induced cutaneous
      tissue injury, represents a clinical marker for non-melanoma skin cancer (NMSC)
      risk. However, the innate immune mechanisms controlling sunburn development are
      not considered relevant in NMSC etiology, and remain poorly investigated. Here we
      found that CD1d knockout (CD1d(-/-)) mice resist UVB-induced cutaneous tissue
      injury and inflammation compared with wild-type (WT) mice. This resistance was
      coupled with a faster epithelial tissue healing response. In contrast, the skins
      of UVB-irradiated invariant NKT cell-knockout (Jalpha18(-/-)) and NKT cell
      deficient (TCRalpha(-/-)) mice, which express CD1d but are deficient in CD1d
      dependent NKT cells, exhibited as much cutaneous tissue injury and inflammation
      as WT mice. In the absence of NKT cells, CD1d-deficient keratinocytes, dendritic
      cells, and macrophages exhibited diminished basal and stress-induced levels of
      pro-inflammatory mediators. Thus, our findings identify an essential role for
      CD1d in promoting UVB-induced cutaneous tissue injury and inflammation. They also
      suggest sunburn and NMSC etiologies are immunologically linked. 

PMID- 23867898
TI  - Content validation of the international classification of functioning, disability
      and health core set for stroke from gender perspective using a qualitative
      approach.
AB  - BACKGROUND: The extended ICF Core Set for stroke is an application of the
      International Classification of Functioning, Disability and Health (ICF) of the
      World Health Organisation (WHO) with the purpose to represent the typical
      spectrum of functioning of persons with stroke. AIM: The objective of the study
      is to add evidence to the content validity of the extended ICF Core Set for
      stroke from persons after stroke taking into account gender perspective. DESIGN
      AND SETTING: A qualitative study design was conducted by using individual
      interviews with women and men after stroke in an in- and outpatient
      rehabilitation setting. METHODS: The sampling followed the maximum variation
      strategy. Sample size was determined by saturation. Concepts from qualitative
      data analysis were linked to ICF categories and compared to the extended ICF Core
      Set for stroke. RESULTS: Twelve women and 12 men participated in 24 individual
      interviews. In total, 143 out of 166 ICF categories included in the extended ICF
      Core Set for stroke were confirmed (women: N.=13; men: N.=17; both genders:
      N.=113). Thirty-eight additional categories that are not yet included in the
      extended ICF Core Set for stroke were raised by women and men. CONCLUSION: This
      study confirms that the experience of functioning and disability after stroke
      shows communalities and differences for women and men. The validity of the
      extended ICF Core Set for stroke could be mostly confirmed, since it does not
      only include those areas of functioning and disability relevant to both genders
      but also those exclusively relevant to either women or men. CLINICAL
      REHABILITATION IMPACT: Further research is needed on ICF categories not yet
      included in the extended ICF Core Set for stroke.

PMID- 23867899
TI  - Gestational diabetes in Turkmenistan: implementation of a screening program and
      first results.
AB  - PURPOSE: Data on the prevalence of gestational diabetes (GDM) is not available
      for Turkmenistan or any other central Asian country with large energy resources
      and rapidly increasing wealth and rates of obesity. We initiated a screening
      program to determine the prevalence of and the risk factors for GDM in
      Turkmenistan. METHODS: Between March 2008 and March 2011, all pregnant women
      presenting to the Ene-Maehri-Merkezi perinatal center in Ashgabat before week 34
      of pregnancy received a glucose screening test (after 26 weeks of pregnancy; 50 g
      glucose). If 60-min glucose was >=7.8 mmol/l, an oral glucose tolerance test
      (oGTT) (75gr) was performed. GDM was diagnosed if >=1 glucose values were
      abnormal (>=5.0, >=10.0, >=8.0 mmol/l at 0-, 60-, 120-min, respectively). Birth
      weight, 30 min glucose, and APGAR (1, 5, and 10 min) were recorded for all
      newborns. RESULTS: Of 1,738 women, 22.7 % had a pathological screening test. 70 %
      of these, underwent an oGTT and of these, 39.5 % had GDM (overall prevalence 6.3
      %). Age, BMI, parity, and blood pressure were associated with screening glucose
      (all p < 0.001). In a multivariate analysis, age, BMI, and family history for
      diabetes were associated with GDM. Newborns from affected mothers were heavier
      (3,622 +/- 435 vs. 3,480 +/- 464 g, p = 0.007) and developed postnatal
      hypoglycaemia more often (21.6 vs. 9.3 %, p = 0.001), while there was no
      difference in APGAR. CONCLUSIONS: GDM is a relevant problem in Turkmenistan and
      probably also in other central Asian countries. The prevalence is similar to
      other developing countries such as India or China. Risk factors are comparable to
      those determined in other parts of the world.

PMID- 23867900
TI  - Enhanced depth imaging optical coherence tomography findings associated with
      serous retinal detachment in preeclampsia.

PMID- 23867901
TI  - Bladder perforation after TVT-Secur procedure: how secure is TVT-Secur?
AB  - BACKGROUND: A rare but challenging complication of midurethral tape procedures is
      perforation of the tape through the bladder wall. CASES: We saw three patients in
      whom unrecognized bladder perforation during TVT-Secur procedures occurred. It
      took an average follow-up time of 11 months before the bladder perforations were
      identified by introital ultrasound. Complete excision of the mesh was achieved
      endoscopically (TURP resectoscope) and/or by traditional vaginal tape removal
      techniques. Following tape removal, there has been no recurrence of urinary tract
      infections, and the irritative voiding symptoms have resolved in all three cases.
      CONCLUSIONS: Bladder perforation after mini-sling procedures can be managed using
      a combined transurethral/vaginal approach. This technique is minimally invasive,
      safe, and successful. Careful introital ultrasound should be performed in
      patients presenting with new lower urinary tract symptoms after sling surgery to
      avoid delays in diagnosing bladder perforation.

PMID- 23867902
TI  - Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast
      cancer cells via suppression of EGFR-mediated Akt and MAPK pathways.
AB  - Platycodin D (PD), an active triterpenoid saponin from Platycodon grandiflorum,
      has been known to inhibit the proliferation of a variety of cancer cells, but the
      effect of PD on the invasiveness of cancer cells is largely unknown. In this
      study, we first determined the molecular mechanism by which PD inhibits the
      migratory and invasive abilities of the highly metastatic MDA-MB-231 breast
      cancer cell line. We demonstrated that a non-cytotoxic concentration of PD
      markedly suppressed wound healing migration, invasion through the matrigel, and
      adhesion to an ECM-coated substrate in a dose-dependent manner. Moreover, PD
      inhibited cell invasion by reducing matrix metalloproteinase (MMP)-9 enzyme
      activity and mRNA expression. Western blot analysis indicated that PD potently
      suppressed the phosphorylation of extracellular signal-regulated kinase (ERK),
      p38, and c-Jun N-terminal kinase (JNK) as well as blocked the
      phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. Furthermore, PD
      treatment inhibited the DNA binding activity of NF-kappaB, which is known to
      mediate the expression of epidermal growth factor receptor (EGFR), as observed by
      electrophoretic mobility shift assay. Specific mechanisms of action exerted by PD
      involved the downregulation of EGFR and the inhibition of EGF-induced activation
      of the EGFR, MAPK, and PI3K/Akt pathways. The in vivo studies showed that PD
      significantly inhibited the growth of MDA-MB-231 xenograft tumors in BALB/c nude
      mice. These results suggest that PD might be a potential therapeutic candidate
      for the treatment of breast cancer metastasis. 

PMID- 23867903
TI  - Formononetin potentiates epirubicin-induced apoptosis via ROS production in HeLa
      cells in vitro.
AB  - The frequent development of multidrug resistance (MDR) hampers the efficacy of
      available anticancer drugs in treating cervical cancer. In this study, we aimed
      to use formononetin (7-hydroxy-4'-methoxyisoflavone), a potential herbal
      isoflavone, to intensify the chemosensitivity of human cervical cancer HeLa cells
      to epirubicin, an anticancer drug. The reactive oxygen species (ROS) levels were
      correlated with MDR modulation mechanisms, including the transporter inhibition
      and apoptosis induction. Our results revealed that formononetin significantly
      enhanced the cytotoxicity of epirubicin. Co-incubation of epirubicin with
      formononetin increased the ROS levels, including hydrogen peroxide and superoxide
      free radicals. Epirubicin alone markedly increased the mRNA expression of MDR1,
      MDR-associated protein (MRP) 1, and MRP2. In contrast, formononetin alone or
      combined treatment decreased the mRNA expression of MRP1 and MRP2. This result
      indicates that efflux transporter-mediated epirubicin resistance is inhibited at
      different degrees by the addition of formononetin. This isoflavone significantly
      intensified epirubicin uptake into HeLa cells. Apoptosis was induced by
      formononetin and/or epirubicin, as signified by nuclear DNA fragmentation,
      chromatin condensation, increased sub-G1 and G2/M phases. The cotreatment
      triggered the mitochondrial apoptotic pathway indicated by increased Bax-to-Bcl-2
      expression ratio, loss of mitochondrial membrane potential, and significant
      activation of caspase-9 and -3. In addition, extrinsic/caspases-8 apoptotic
      pathway was also induced by the cotreatment. N-acetyl cysteine abrogated these
      events induced by formononetin, supporting the involvement of ROS in the MDR
      reversal mechanism. This study pioneered in demonstrating that formononetin may
      potentiate the cytotoxicity of epirubicin in HeLa cells through the ROS-mediated
      MRP inhibition and concurrent activation of the mitochondrial and death receptor
      pathways of apoptosis. Hence, the circumvention of pump and non-pump resistance
      using formononetin and epirubicin may pave the way for a powerful
      chemotherapeutic regimen for treating human cervical cancer. 

PMID- 23867904
TI  - The antioxidant effect of the mesoionic compound SYD-1 in mitochondria.
AB  - The sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate]
      possesses important antitumor activity against Sarcoma 180 and Ehrlich tumors. We
      previously showed that SYD-1 depresses mitochondrial phosphorylation efficiency,
      which could be involved in its antitumoral activity. Considering the important
      role of mitochondria in the generation of reactive oxygen species (ROS) and the
      involvement of ROS in cell death mechanisms, we evaluated the effects of SYD-1 on
      oxidative stress parameters in rat liver mitochondria. SYD-1 (0.5 and
      0.75MUmolmg(-1) protein) inhibited the lipoperoxidation induced by Fe(3+)/ADP
      oxoglutarate by approximately 75% and promoted total inhibition at the highest
      concentration tested (1.0MUmolmg(-1) protein). However, SYD-1 did not affect
      lipoperoxidation started by peroxyl radicals generated by alpha-alpha'
      azodiisobutyramidine dihydrochloride. The mesoionic compound (0.25-1.0MUmolmg(-1)
      protein) demonstrated an ability to scavenge superoxide radicals, decreasing
      their levels by 9-19%. The activities of catalase and superoxide dismutase did
      not change in the presence of SYD-1 (0.25-1.0MUmolmg(-1) protein). SYD-1
      inhibited mitochondrial swelling dependent on the formation/opening of the
      permeability transition pore induced by Ca(2+)/phosphate by approximately 30%
      (1.0MUmolmg(-1) protein). When Ca(2+)/H2O2 were used as inducers, SYD-1 inhibited
      swelling only by approximately 12% at the same concentration. NADPH oxidation was
      also inhibited by SYD-1 (1.0MUmolmg(-1) of protein) by approximately 48%. These
      results show that SYD-1 is able to prevent oxidative stress in isolated
      mitochondria and suggest that the antitumoral activity of SYD-1 is not mediated
      by the increasing generation of ROS. 

PMID- 23867905
TI  - Acinetobacter phage genome is similar to Sphinx 2.36, the circular DNA copurified
      with TSE infected particles.
AB  - While analyzing plasmids of Acinetobacter sp. DS002 we have detected a circular
      DNA molecule pTS236, which upon further investigation is identified as the genome
      of a phage. The phage genome has shown sequence similarity to the recently
      discovered Sphinx 2.36 DNA sequence co-purified with the Transmissible Spongiform
      Encephalopathy (TSE) particles isolated from infected brain samples collected
      from diverse geographical regions. As in Sphinx 2.36, the phage genome also codes
      for three proteins. One of them codes for RepA and is shown to be involved in
      replication of pTS236 through rolling circle (RC) mode. The other two
      translationally coupled ORFs, orf106 and orf96, code for coat proteins of the
      phage. Although an orf96 homologue was not previously reported in Sphinx 2.36, a
      closer examination of DNA sequence of Sphinx 2.36 revealed its presence
      downstream of orf106 homologue. TEM images and infection assays revealed
      existence of phage AbDs1 in Acinetobacter sp. DS002. 

PMID- 23867906
TI  - Mitochondrial inner membrane lipids and proteins as targets for decreasing
      cardiac ischemia/reperfusion injury.
AB  - A major manifestation of coronary artery disease is cardiac ischemia/reperfusion
      injury, with the extent of injury directly relating to short- and long-term
      prognosis. Emerging evidence suggests that mitochondrial dysfunction is centrally
      involved in ischemia/reperfusion injury. In this review, we summarize the role of
      mitochondria in the etiology of ischemia/reperfusion injury. We attempt to
      highlight emerging areas for cardiac mitochondrial medicine and discuss recent
      advances regarding the molecular composition of inner membrane channels. We
      discuss interactions between lipids and proteins in the inner mitochondrial
      membrane, and the ever-evolving nature of this relationship during
      ischemia/reperfusion. Potentially novel treatments influencing the biophysical
      properties of inner membrane lipids (such as cardiolipin) are presented. Finally,
      we point to areas where future study is needed to expand and improve our
      understanding of mitochondrial pathophysiology during cardiac
      ischemia/reperfusion. 

PMID- 23867908
TI  - DRainage Or Pericardiocentesis alone for recurrent nonmalignant, nonbacterial
      pericardial effusions requiring intervention: rationale and design of the DROP
      trial, a randomized, open-label, multicenter study.
AB  - OBJECTIVES: Evidence to support the use of pericardial drainage instead of simple
      pericardiocentesis for nonmalignant pericardial effusions refractory to medical
      therapy is based on observational studies and experts' opinions, rather than
      randomized trials. The aim of the present trial is to fill this knowledge gap and
      to provide a stronger base of evidence to support a specific interventional
      treatment in this setting. METHODS: DRainage Or Pericardiocentesis (DROP) alone
      for recurrent nonmalignant, nonbacterial pericardial effusions requiring
      intervention is a randomized, open-label and multicenter study. The primary
      efficacy endpoints are the incidence of recurrent pericardial effusion, and the
      need for additional pericardiocentesis or cardiac surgery at 12 months. Secondary
      endpoints are hospital length stay, disease-related admission and overall
      mortality. Safety and complications rates of each intervention will be also
      assessed. IMPLICATIONS AND CONCLUSION: The DROP trial will be the first
      multicenter randomized trial to evaluate the efficacy and safety of
      pericardiocentesis versus pericardiocentesis and extended pericardial drainage
      for recurrent nonmalignant, nonbacterial pericardial effusions refractory to
      medical therapy and requiring interventional treatments (ClinicalTrials.gov
      Identifier: NCT01665495).

PMID- 23867907
TI  - Cardiac oxidative stress in a mouse model of neutral lipid storage disease.
AB  - Cardiac oxidative stress has been implicated in the pathogenesis of hypertrophy,
      cardiomyopathy and heart failure. Systemic deletion of the gene encoding adipose
      triglyceride lipase (ATGL), the enzyme that catalyzes the rate-limiting step of
      triglyceride lipolysis, results in a phenotype characterized by severe steatotic
      cardiac dysfunction. The objective of the present study was to investigate a
      potential role of oxidative stress in cardiac ATGL deficiency. Hearts of mice
      with global ATGL knockout were compared to those of mice with cardiomyocyte
      restricted overexpression of ATGL and to those of wildtype littermates. Our
      results demonstrate that oxidative stress, measured as lucigenin
      chemiluminescence, was increased ~6-fold in ATGL-deficient hearts. In parallel,
      cytosolic NADPH oxidase subunits p67phox and p47phox were upregulated 4-5-fold at
      the protein level. Moreover, a prominent upregulation of different inflammatory
      markers (tumor necrosis factor alpha, monocyte chemotactant protein-1,
      interleukin 6, and galectin-3) was observed in those hearts. Both the oxidative
      and inflammatory responses were abolished upon cardiomyocyte-restricted
      overexpression of ATGL. Investigating the effect of oxidative and inflammatory
      stress on nitric oxide/cGMP signal transduction we observed a ~2.5-fold
      upregulation of soluble guanylate cyclase activity and a ~2-fold increase in
      cardiac tetrahydrobiopterin levels. Systemic treatment of ATGL-deficient mice
      with the superoxide dismutase mimetic Mn(III)tetrakis (4-benzoic acid) porphyrin
      did not ameliorate but rather aggravated cardiac oxidative stress. Our data
      suggest that oxidative and inflammatory stress seems involved in lipotoxic heart
      disease. Upregulation of soluble guanylate cyclase and cardiac
      tetrahydrobiopterin might be regarded as counterregulatory mechanisms in cardiac
      ATGL deficiency. 

PMID- 23867909
TI  - Association of high-risk scores for obstructive sleep apnea with symptomatic
      bradyarrhythmias.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) may have an association with
      bradyarrhythmias but often remains undiagnosed. Our aim was to determine if
      patients with a high risk of OSA attending our cardiology clinics had an
      association with symptomatic bradyarrhythmias, as this information might lead to
      changes in management strategy. METHODS: The Berlin questionnaire was used to
      assess risk of OSA in 190 patients, and they were divided into high-risk or low
      risk groups. Demographic data and medical histories were recorded and patients
      groups were compared with t-tests and chi-square tests. A multivariate regression
      analysis was done to correct for confounding variables. RESULTS: The mean age of
      our sample population was 63.0 +/- 14.7 years with a mean BMI of 29.5 +/- 7.8
      kg/m2. Using the Berlin questionnaire, 41.3% of the patients were classified as
      high risk; 15.7% of the patients had a known diagnosis of OSA. Between high-risk
      and low-risk groups, there was no significant difference in the prevalence of
      bradyarrhythmias (22.5 vs. 15.2% P = 0.21), symptomatic sinus node dysfunction
      (14.4 vs. 11.4% P = 0.66) or atrioventricular block (10.8 vs. 6.3% P = 0.33). A
      multivariable logistic regression analysis demonstrated that dyslipidemia had the
      strongest association with a high risk for OSA, but not bradyarrhythmias.
      CONCLUSIONS: Based on the Berlin questionnaire, patients at a high risk for OSA
      did not have an increased prevalence of bradyarrhythmias. More studies are needed
      to assess the utility of evaluating patients with bradyarrhythmias for OSA prior
      to implanting permanent pacing devices.

PMID- 23867910
TI  - Prognostic role of aldosterone in patients with acute coronary syndrome: short
      and medium term follow-up.
AB  - AIMS: Different studies have shown a correlation between aldosterone,
      atherosclerosis and ischemia in the past decade. Evidence exists for the
      relationship between high levels of aldosterone and augmented risk of
      cardiovascular diseases, such as hypertension, cardiac failure, coronary artery
      disease and stroke. The objective of this study was to determine the prognostic
      role of aldosterone in patients with myocardial infarction. METHODS: The study
      population included 96 consecutive patients admitted to our department for ST
      elevated and non-ST-elevated myocardial infarction from June 2009 to March 2012.
      Plasma aldosterone levels were measured at admission to hospital in all patients.
      A 2-year prospective follow-up was performed, and fatal events and non-fatal
      events, such as reinfarction, congestive heart failure and arrhythmias, were
      recorded. RESULTS: Aldosterone levels at admission were associated with incidence
      of congestive heart failure (P = 0.02), ventricular arrhythmias (P = 0.01) and
      all complications (P = 0.003) after 1-month follow-up. Moreover, high aldosterone
      levels gave important information in the medium term (24 +/- 6 months).
      Specifically, aldosterone was a predictive variable of reinfarction (P < 0.0001),
      congestive heart failure (P < 0.0001) and adverse events (P = 0.0002). The
      logistic regression analysis confirmed these results and showed that aldosterone
      may be predictive of adverse events at medium-term follow-up (odds ratio 1.1, 95%
      confidence interval 1.03-1.15, P = 0.02). CONCLUSION: These data show a strong
      and significant correlation between plasma aldosterone levels at admission for
      myocardial infarction and fatal and nonfatal adverse events. Aldosterone appears
      to be a main marker of adverse clinical outcome, in accordance with the
      literature. These data suggest the need to identify whether antialdosteronic drug
      treatment, applied acutely in patients with aldosterone elevation, can influence
      favorably the prognosis of patients with myocardial infarction.

PMID- 23867911
TI  - The un-natural history of an adolescent with combined congenital and acquired
      heart disease.
AB  - This study describes the un-natural history of a 16-year-old patient, presenting
      with a critical bicuspid aortic valve stenosis, who was initially treated in the
      neonatal period and later with a valvuloplasty. This focused the attention on
      palliative interventions that, in young adulthood or middle age, are usually
      related to several complications, until heart transplantation. The other
      important aspect of this case is the presence of a coronary atherosclerotic
      plaque producing a significant obstruction, in the setting of haemodynamic acute
      postoperative failure caused by the sudden aortic valve laceration and
      insufficiency. This favoured the transmural myocardial antero-septal evolution of
      the myocardial ischaemic-reperfusion damage. This case is peculiar in that it
      presents two unrelated entities in their natural history. The coronary lesion was
      an unexpected finding in an adolescent with congenital heart disease. The
      severity of the coronary lesion became haemodynamically significant as a
      combination of the hypoperfusion due to the massive aortic valve regurgitation
      following the acute failure of the aortic valve plasty and the vasoconstriction
      of the eccentric speared segment. Once again, the complete understanding of grown
      up patients with congenital hart disease is mandatory together with the point
      that a close collaboration of a multidisciplinary team is essential for
      appropriate operative timing and planning the most suitable treatment option.
      Acquired heart diseases can rarely present in association in this group of
      patients and need to be taken into account. 

PMID- 23867912
TI  - M-mode echocardiographic values in a cohort of young healthy individuals.
AB  - OBJECTIVES: To determine normal M-mode values in healthy young adults and to
      evaluate whether these values differ among those in whom echocardiography was
      performed routinely and those in whom echocardiography was performed based on
      clinical grounds. METHODS: A cross-sectional study evaluating a large cohort of
      young academy applicants of the Israeli air force in the years 1994-2010. Studies
      were divided into those performed routinely and those performed because of
      abnormal ECG or physical examination findings. Echocardiographic variables were
      compared between the two groups and values are expressed as mean +/- SD. RESULTS:
      Echocardiography was performed routinely in 3525 applicants (age 18.5 +/- 1.0
      years) and following a clinical referral in 3517 applicants (age 18.2 +/- 0.9
      years). Those in whom echocardiography was performed routinely had slightly
      higher left ventricular end-systolic diameter (31.2 +/- 3.3  vs. 30.7 +/- 3.4 mm;
      P < 0.0001) and aortic root diameter (28.5 +/- 2.1 vs. 27.9 +/- 2.2 mm; P <
      0.0001), and slightly lower left ventricular mass index (108.8 +/- 15.8  vs.
      109.9 +/- 16.5 g/m; P = 0.005). No differences were noted between the two groups
      in left atrial diameter, left ventricular end-diastolic volume, posterior wall
      thickness and interventricular septum thickness. CONCLUSION: Certain M-mode
      characteristics may differ (although to a slight degree) in young healthy
      individuals with electrocardiographic and physical findings compared with those
      with normal physical examination and electrocardiography.

PMID- 23867913
TI  - Conventional versus frozen elephant trunk surgery for extensive disease of the
      thoracic aorta.
AB  - OBJECTIVE: To compare early and mid-term outcomes after repair of extensive
      aneurysm of the thoracic aorta using the conventional elephant trunk or frozen
      elephant trunk (FET) procedures. METHODS: Fifty-seven patients with extensive
      thoracic aneurysmal disease were treated using elephant trunk (n = 36) or FET (n
      = 21) procedures. Patients with aortic dissection, descending thoracic aorta
      (DTA) diameter less than 40 mm, and thoracoabdominal aneurysms were excluded from
      the analysis, as were those who did not undergo antegrade selective cerebral
      perfusion during circulatory arrest. Short-term and mid-term outcomes were
      compared according to elephant trunk/FET surgical management. RESULTS:
      Preoperative and intraoperative variables were similar in the two groups, except
      for a higher incidence of female sex, coronary artery disease and associated
      procedures in elephant trunk patients. Hospital mortality (elephant trunk: 13.9%
      versus FET: 4.8%; P = 0.2), permanent neurologic dysfunction (elephant trunk:
      5.7% versus FET: 9.5%; P = 0.4) and paraplegia (elephant trunk: 2.9% versus FET:
      4.8%; P = 0.6) rates were similar in the two groups. Follow-up was 100% complete.
      In the elephant trunk group, 68.4% of patients did not undergo a second-stage
      procedure during follow-up for a variety of reasons. Of these patients, the DTA
      diameter was greater than 51 mm in 72.2% and two (6.7%) died due to aortic
      rupture while awaiting stage-two intervention. Endovascular second-stage
      procedures were successfully performed in all FET patients with residual DTA
      aneurysmal disease (n = 3), whereas nine of 11 elephant trunk patients who
      returned for second-stage procedures required conventional surgical replacement
      through a lateral thoracotomy. Kaplan-Meier estimate of 4-year survival was 75.8
      +/- 7.6 and 72.8 +/- 10.6 in elephant trunk and FET patients, respectively (log
      rank P = 0.8). CONCLUSION: In patients with extensive aneurysmal disease of
      thoracic aorta, elephant trunk and FET procedures seem to be associated with
      similar satisfactory early and mid-term outcomes. The FET approach leads to
      single-stage treatment of all aortic disease in most patients, and facilitates
      endovascular second-stage treatment in patients with residual DTA disease. The
      elephant trunk staged-approach appears to leave a considerable percentage of
      patients at risk for adverse aortic events.

PMID- 23867914
TI  - Reactive oxygen species involvement in apoptosis and mitochondrial damage in Caco
      2 cells induced by enniatins A, A1, B and B1.
AB  - The cytotoxic effects, the generation of reactive oxygen species (ROS) and lipid
      peroxidation (LPO) as well as the cell cycle disruption, the induction of
      apoptosis and changes in mitochondrial membrane potential (DeltaPsim) as a
      function of increasing time have been determined in human colorectal
      adenocarcinoma (Caco-2) cells after exposure to enniatins (ENs) A, A1, B and B1.
      IC50 values obtained by the MTT and Neutral Red assay, after 24, 48 and 72 h of
      exposure ranged from 0.5+/-0.1 to >15 MUM. A significant increase (p<=0.05) in
      ROS generation and LPO production, as determined by the fluorescent probe H2
      DCFDA and TBARS method respectively, was observed for all mycotoxins tested at
      3.0 MUM concentration. The highest increase in ROS generation (2.6 fold higher
      than control) and LPO production (111%, as compared to control) was observed with
      EN A. Cell cycle was significantly arrested at G2/M phase after 24 h of exposure
      to EN A, A1, B1, whereas after 72 h of exposure an arrest in S phase was observed
      almost for all mycotoxins tested. Moreover, after 24 and 48 h of exposure, ENs
      increased the early apoptotic cells, whereas after 72h of exposure necrosis was
      observed. In addition the loss of DeltaPsim was produced on Caco-2 cells after
      ENs exposure. ENs A, A1, B and B1 cytotoxicity involved early ROS generation that
      induced LPO oxidative damage, apoptosis and necrosis via the mitochondrial
      pathway. ENs A, A1 and B1 induced DNA damage. However the same effects cannot be
      proposed for EN B. Further studies on the toxicological effects induced by ENs A,
      A1, B and B1 are needed.

PMID- 23867915
TI  - Toxicokinetic profiles of alpha-ketoglutarate cyanohydrin, a cyanide
      detoxification product, following exposure to potassium cyanide.
AB  - Poisoning by cyanide can be verified by analysis of the cyanide detoxification
      product, alpha-ketoglutarate cyanohydrin (alpha-KgCN), which is produced from the
      reaction of cyanide and endogenous alpha-ketoglutarate. Although alpha-KgCN can
      potentially be used to verify cyanide exposure, limited toxicokinetic data in
      cyanide-poisoned animals are available. We, therefore, studied the toxicokinetics
      of alpha-KgCN and compared its behavior to other cyanide metabolites, thiocyanate
      and 2-amino-2-thiazoline-4-carboxylic acid (ATCA), in the plasma of 31 Yorkshire
      pigs that received KCN (4mg/mL) intravenously (IV) (0.17 mg/kg/min). alpha-KgCN
      concentrations rose rapidly during KCN administration until the onset of apnea,
      and then decreased over time in all groups with a half-life of 15 min. The
      maximum concentrations of alpha-KgCN and cyanide were 2.35 and 30.18 MUM,
      respectively, suggesting that only a small fraction of the administered cyanide
      is converted to alpha-KgCN. Although this is the case, the alpha-KgCN
      concentration increased >100-fold over endogenous concentrations compared to only
      a three-fold increase for cyanide and ATCA. The plasma profile of alpha-KgCN was
      similar to that of cyanide, ATCA, and thiocyanate. The results of this study
      suggest that the use of alpha-KgCN as a biomarker for cyanide exposure is best
      suited immediately following exposure for instances of acute, high-dose cyanide
      poisoning.

PMID- 23867917
TI  - An anion-controlled crystal growth route to Zn2GeO4 nanorods for efficient
      photocatalytic conversion of CO2 into CH4.
AB  - For photoreduction of CO2 into solar fuels driven by photocatalysis, a means to
      convert solar energy into chemical energy, a semiconductor photocatalyst with a
      specific crystal surface and high chemical stability is expected to achieve high
      activity and selectivity. Here, (110) facets exposed Zn2GeO4 nanorods with
      different aspect ratios were prepared by the ion exchange reaction between
      Na2GeO3 colloidal solution and various zinc salt solutions. The aspect ratio of
      Zn2GeO4 can be adjusted in the wide range from 2.5:1 to 20:1, depending on the
      acid radical. In this synthetic route, the Na2GeO3 precursor is a strong base,
      but strong acids such as HCl, HNO3 and H2SO4 as by-products were formed, meaning
      that the Zn2GeO4 single-crystal nanorods have good chemical stability in acid as
      well as in base. The excellent hydrothermal stability for the Zn2GeO4 nanorods in
      NaOH solution provides a simple method to obtain a hydroxylated surface for high
      performance in the photocatalytic conversion of CO2 and H2O to hydrocarbons
      fuels.

PMID- 23867916
TI  - Alpha, beta-unsaturated lactones 2-furanone and 2-pyrone induce cellular DNA
      damage, formation of topoisomerase I- and II-DNA complexes and cancer cell death.
AB  - The alpha, beta-unsaturated lactones 2-furanone and 2-pyrone are part of the
      chemical structure of a variety of naturally occurring compounds (e.g.,
      cardenolides, bufadienolides, acetogenins, coumarins, and food-flavoring
      furanones), some of which have shown anticancer activity and/or DNA damaging
      effects. Here we report that 2-furanone and 2-pyrone induce cellular DNA damage
      (assessed by the comet assay and the gamma-H2AX focus assay) and the formation of
      topoisomerase I- and topoisomerase II-DNA complexes in cells (visualized and
      quantified in situ by the TARDIS assay). Cells mutated in BRCA2 (deficient in
      homologous recombination repair) were significantly hypersensitive to the
      cytotoxic activity of 2-pyrone, therefore suggesting that BRCA2 plays an
      important role in the repair of DNA damage induced by this lactone. Both lactones
      were cytotoxic in A549 lung cancer cells at lower concentrations than in MRC5 non
      malignant lung fibroblasts. The possible involvement of 2-furanone and 2-pyrone
      in the anticancer and DNA-damaging activities of compounds containing these
      lactones is discussed. 

PMID- 23867918
TI  - Interferon-induced proteins with tetratricopeptide repeats 1 and 2 are cellular
      factors that limit hepatitis B virus replication.
AB  - Interferon (IFN)-alpha is able to stimulate many cellular genes and inhibit the
      replication of various viruses. However, it is unknown whether some IFN
      stimulated genes (ISGs) specifically inhibit hepatitis B virus (HBV) replication.
      Therefore, we attempted to identify ISGs with antiviral activities against HBV.
      Knockdown of IFN-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1
      and IFIT2) in HepG2.2.15 led to markedly increased HBV replication. Consistently,
      this effect was verified by transient transfection with a replication-competent
      HBV clone in HepG2 and Huh7. However, IFN-alpha stimulation could override the
      knockdown by siRNAs and enhance the expression of IFIT1 and IFIT2, leading to
      reduced HBV replication. Silencing of IFIT1 or IFIT2 decreased the expression of
      the corresponding genes while other ISGs like MxA were not affected. Northern
      blot analysis showed that IFIT1 and IFIT2 knockdown slightly increased the levels
      of HBV 3.5, 2.4 and 2.1 kb transcripts, while IFIT1 and IFIT2 overexpression did
      not change their levels. Consistently, the reporter assays with HBV promoters
      demonstrated that IFIT1 and IFIT2 differentially but only modestly regulated HBV
      promoter activity. Thus, IFIT1 and IFIT2 contribute significantly to the
      regulation of HBV replication, likely at both transcriptional and
      posttranscriptional steps.

PMID- 23867919
TI  - The mental health benefits and costs of Sabbath observance among Orthodox Jews.
AB  - This study aimed to examine the perceived psychological costs and benefits of
      Sabbath (Shabbos) observance among 13 practising Jews, 9 UK residents and 4 US
      residents. Emerging themes were as follows: Shabbos as a special day, giving time
      to contemplate on profound issues, withdrawal and rest from mundane concerns, and
      deepening relationships. These aspects can potentially improve feelings of mental
      well-being, and were indeed often said to do so. Some difficulties were
      described: some found they were prone to worry more on Shabbos because of the
      freedom from distractions, and there were reports of the difficulties of
      explaining to non-Jewish work colleagues the religious need to be free from work
      commitments. These findings were related to the literature on religious ritual
      observance and generally accord with other work in anthropology and psychology of
      religion examining the psychological impact of ritual. Work on the mental health
      implications of ritual observance needs to be expanded. It has received only
      limited attention, and understanding has been constrained by a misleading
      confusion between ritual and obsessionality. Other impacts of religion on mental
      health are better documented and understood, and religious ritual and its impact
      needs further documentation and attention. 

PMID- 23867920
TI  - Effect of lip closure on early maxillary growth in patients with cleft lip and
      palate.
AB  - IMPORTANCE: Debate continues about the cause of midfacial growth disturbance in
      patients with facial clefts. OBJECTIVE: To evaluate the functional effect of
      surgical closure of the lip before palatal closure according to the technique by
      Delaire on early maxillary growth in patients with complete unilateral cleft lip
      and palate. DESIGN, SETTING, AND PARTICIPANTS: Twenty-two patients with
      unilateral cleft lip and palate were studied using plaster casts obtained at the
      time of cheilorhinoplasty and 6 months later before palatal closure. The
      interrupted lateral muscles were anatomically repositioned using the surgical
      technique by Delaire. No patients had received preoperative orthodontic treatment
      or a passive palatal plate. Cast analyses were performed using a digital caliper.
      MAIN OUTCOMES AND MEASURES: Landmark positioning was performed 3 times by 2
      different examiners to define intraobserver and interobserver differences. The
      final maxilla dimensions were recorded as the distances between the mean landmark
      positions. Using the t test, dimensions obtained before palatal closure were
      compared with dimensions obtained before lip closure. RESULTS: The method allowed
      good reproducibility. Functional closure of the lip significantly narrowed the
      transverse anterior cleft areas by -2.36 mm (P < .05). Sagittal variables were
      increased by 1.68 mm on the nonaffected side and by 1.48 mm on the affected side
      (P < .05 for both). CONCLUSIONS AND RELEVANCE: Functional closure according to
      the technique by Delaire narrows the transverse dimensions of the maxilla, while
      simultaneously preserving initial sagittal growth. LEVEL OF EVIDENCE: 4.

PMID- 23867921
TI  - Irony comprehension and context processing in schizophrenia during remission--a
      functional MRI study.
AB  - Schizophrenic patients have Theory of Mind (ToM) deficits even during remission,
      but it is yet unknown whether this could be influenced. We examined the neural
      correlates of irony understanding in schizophrenic patients, as an indicator of
      ToM capacity, and evaluated how linguistic help inserted into the context phase
      could affect irony comprehension. Schizophrenic patients in remission and healthy
      controls were subjected to event-related functional MRI scanning while performing
      irony, 'irony with linguistic help', and control tasks. Patients understood irony
      significantly worse than healthy controls. The patients showed stronger brain
      activity in the parietal and frontal areas in the early phase of irony task,
      however the healthy controls exhibited higher activation in frontal, temporal and
      parietal regions in the latter phase of the irony task. Interestingly the
      linguistic help not only improved the patients' ToM performance, but it also
      evoked similar activation pattern to healthy controls. 

PMID- 23867922
TI  - Pre-attentive sensitivity to vowel duration reveals native phonology and predicts
      learning of second-language sounds.
AB  - In some languages (e.g. Czech), changes in vowel duration affect word meaning,
      while in others (e.g. Spanish) they do not. Yet for other languages (e.g. Dutch),
      the linguistic role of vowel duration remains unclear. To reveal whether Dutch
      represents vowel length in its phonology, we compared auditory pre-attentive
      duration processing in native and non-native vowels across Dutch, Czech, and
      Spanish. Dutch duration sensitivity patterned with Czech but was larger than
      Spanish in the native vowel, while it was smaller than Czech and Spanish in the
      non-native vowel. An interpretation of these findings suggests that in Dutch,
      duration is used phonemically but it might be relevant for the identity of
      certain native vowels only. Furthermore, the finding that Spanish listeners are
      more sensitive to duration in non-native than in native vowels indicates that a
      lack of duration differences in one's native language could be beneficial for
      second-language learning. 

PMID- 23867923
TI  - Matching cellular dimensions with molecular sizes.
AB  - This Commentary discusses the spatial perception of receptors and their nanoscale
      organization at the surface of the lymphocyte membrane. 

PMID- 23867924
TI  - Platelet-macrophage partnership in innate immunity and inflammation.

PMID- 23867925
TI  - Control of T(FH) differentiation by a microRNA cluster.

PMID- 23867926
TI  - NLRP3 inflammasome activation: CD36 serves double duty.

PMID- 23867927
TI  - The IL-20 cytokine subfamily: bad guys in host defense?

PMID- 23867945
TI  - Inflammatory bowel diseases: a dysfunction of brain-gut interactions?
AB  - The gut has the capacity to function as an autonomous organ. However, in normal
      conditions, the gut and the central nervous system talk to each other through the
      autonomic nervous system (ANS), represented by the sympathetic (i.e. the
      splanchnic nerves) and the parasympathetic nervous system (i.e. the vagus nerve
      and the sacral parasympathetic pelvic nerves). The brain is able to integrate
      inputs coming from the digestive tract inside a central autonomic network
      organized around the hypothalamus, limbic system and cerebral cortex and in
      return to modify the ANS and the hypothalamic pituitary adrenal axis (HPA axis).
      An abnormal functioning of these brain-gut interactions has been described in
      irritable bowel syndrome (IBS) classically considered as a biopsychosocial model
      where stress plays a promoting role. Inflammatory bowel diseases (IBD) result
      from an inappropriate inflammatory response to intestinal microbes in a
      genetically susceptible host. In this article we review the current knowledge on
      the possible involvement of a dysfunction of brain-gut interactions in the
      pathogeny of IBD as represented by a dysfunction of the ANS, an abnormal HPA axis
      and cholinergic anti-inflammatory pathway, a deleterious effect of stress and
      depression as well as an abnormal coupling of the prefrontal cortex-amygdala
      complex and an abnormal relation between the microbiota and the brain as pro
      inflammatory factors. Therapeutic approaches with the aim to restore an
      equilibrium of these brain-gut interactions are of interest. 

PMID- 23867946
TI  - Prevention of cancer in IBD - a balancing act.
AB  - Inflammation and immunosuppression are two major risk factors for the development
      of carcinogenesis in inflammatory bowel disease (IBD). While the natural history
      of uncontrolled inflammation in the bowel may lead to a higher incidence of
      colorectal cancer (CRC), surveillance colonoscopy has resulted in earlier
      detection of dysplasia and cancer, prompting earlier surgical intervention and
      improved prognosis, while chemoprevention in the form of the anti-inflammatory 5
      aminosalicylate acids and immunosuppression could potentially decrease the
      incidence of CRC. Numerous extra-intestinal cancers such as hepatobiliary and
      pancreatic malignancies, however, are also noted to be more prevalent in IBD
      patients particularly with co-existing primary sclerosing cholangitis. Somewhat
      ironically, however, the medications used to control the inflammation in IBD may
      also be responsible for the development of other cancers. The increased risk of
      lymphoma and skin cancers associated with immunosuppressive medication use may
      potentially be due to loss of immunosurveillance and in the case of lymphoma, the
      presence of oncogenic viruses (i.e., Epstein-Barr virus). Thus the challenge for
      both the treating physician and IBD patient is to balance the risk of any
      potential treatment against patient symptoms and the natural history of
      uncontrolled inflammation from their disease.

PMID- 23867934
TI  - Short-term memory of danger signals and environmental stimuli in immune cells.
AB  - Standard definitions of immunological memory are all built on the idea that once
      infected, animals are protected more efficiently against a second infection. This
      common view overlooks an unavoidable consequence of the exposure of cells to
      pathogens, danger signals and environmental agents in general: stimuli change
      cell properties and activity in a transient yet sustained manner that extends
      beyond the exposure time and modulates the response of cells of both the innate
      and adaptive immune systems to secondary stimulation. We suggest that this
      transient phenomenon represents 'short-term memory' of environmental exposure and
      discuss the evidence that this is mediated by the persistence of long-lived
      regulatory molecules, notably a subset of newly deposited chromatin modifications
      and inducible noncoding RNAs. 

PMID- 23867947
TI  - Endoscopy in inflammatory bowel disease.
AB  - Small bowel imaging and endoscopy in inflammatory bowel disease (IBD) underwent a
      lot of change and advancement in the recent years. Modalities have shifted from
      gastroscopy, colonoscopy and small bowel follow through, to ileo-colonoscopy,
      computed tomography (CT) or magnetic resonance (MR), enteroscopy, wireless video
      capsule endoscopy and balloon assisted enteroscopy. Nowadays endoscopy has a
      major role in the diagnosis of IBD, assessing its extent, treating some of its
      complications (stricture, bleeding), assessing the success of various treatments
      (mucosal healing), and as a predictor of disease course. Wireless capsule
      endoscopy (WCE) is a relatively new "toy" allowing direct, patient friendly,
      visualization of the entire small bowel mucosa. It has gained a substantial role
      in the evaluation of patients with suspected Chron's Disease (CD) and
      indeterminate colitis. WCE has a high positive predictive value in patients with
      suspected CD, when one uses more than two of the International Conference on
      Capsule Endoscopy (ICCE) criteria, and not less important, a very high negative
      predictive value in patients with suspected CD. Its role in patients with known
      CD, assessing their disease activity and extent, its role in assessing
      postsurgical small bowel recurrence and its role in the evaluation of mucosal
      healing are still unclear. Balloon assisted enteroscopy has established its role
      as a complementary tool in cases where there is need of biopsies or treatment
      (dilatation of strictures). The present review will summarize the role of
      endoscopy in the diagnosis of IBD, in assessing its activity, its management,
      interventional endoscopy and cancer surveillance. 

PMID- 23867948
TI  - Reproduction in the patient with inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) often occurs in women of childbearing age and
      requires complex treatment decision. IBD can have profound influences on
      fertility, the course of a pregnancy, child birth and lactation. Many women with
      IBD remain voluntarily childless and patient knowledge of pregnancy related
      issues is generally poor, which can lead to negative views regarding IBD
      treatments. To achieve good clinical outcomes for mother and infant a balance has
      to be struck between the risks of any IBD treatment and the risks of untreated
      IBD. The advent of the biological age has brought another level of complexity.
      While more data demonstrating the safe use in pregnancy have recently emerged,
      effects on infants continue for up to 6 months with important implications on
      vaccination plans. This review discusses recent advances in the field of IBD and
      reproduction. 

PMID- 23867949
TI  - Is there a therapeutic window of opportunity in early inflammatory bowel disease?
      Early stage inflammatory bowel disease: the actual management.
AB  - Traditionally therapy for inflammatory bowel disease (IBD) encompassed a
      sequential approach with subjects treated with 5-ASA products and/or
      corticosteroids initially, and only where failing such treatment, moving on to
      immunomodulator or biologic therapy. In the rheumatologic literature the
      importance of the early introduction of immunosuppressive therapies for
      inflammatory arthropathies has been increasingly recognized, however this concept
      remains much debated in IBD with no clear consensus on the optimal therapeutic
      approach. In this review we discuss how the natural history of IBD provides a
      rationale for the early introduction of the most effective therapy. We outline
      how the experience of early immunosuppressive therapy in rheumatoid arthritis
      informs therapeutic decision making in IBD. We review the evolving treatment
      strategies in IBD and the current evidence supporting the introduction of
      immunosuppressive treatment soon after IBD diagnosis. Finally we discuss the
      importance of selecting appropriate therapeutic endpoints in IBD and review the
      potential risks and benefits of early immunosuppressive treatment strategies in
      IBD. 

PMID- 23867950
TI  - Liver fibrosis: evaluation with diffusion-weighted magnetic resonance imaging in
      patients with chronic liver disease.
AB  - AIM: Liver fibrosis is often a possible evolution of chronic liver disease (CLD),
      with a risk of progression to cirrhosis. This study was designed to determine if
      the measure of apparent diffusion coefficient (ADC) is clinically accurate in the
      staging of fibrosis. METHODS: The study was conducted in the period 2008-2012. We
      recruited 84 patients with CLD. The control group included 67 patients whose
      laboratory, ultrasound and magnetic resonance imaging exams demonstrated liver's
      normal conditions. For ethical reasons, these patients did not undergo liver
      biopsy. Patients were examined using diffusion-weighted magnetic resonance
      imaging with a 1.5 Tesla magnet and with single shot echo-planar technique.
      Patients did undergo liver biopsy and the samples were evaluated with the Metavir
      score (F0-F4), Ishak score (0-6) and Brunt score (0-6). Patients were divided
      into three groups according to the different degree of fibrosis and the ADC was
      compared with U-test of Mann-Whitney. Moreover, it was used the analysis Receiver
      Operating Characteristic (ROC). RESULTS: A significant difference between group 1
      (F0-F1) and group 3 (F3-F4) was found, with P=0.0024 and between group 2 (F2) and
      group 3, with P=0.027, but there was no significant difference of the ADC values
      in group 1 and group 2. CONCLUSION: The study showed a correlation between
      reduction of ADC and increasing of liver fibrosis degree. The ADC seems to be
      useful in staging liver fibrosis in patients with CLD, in particular to
      distinguish the later stages of fibrosis from early and intermediate stages.

PMID- 23867951
TI  - The addition of a large caliber needle during endoscopic ultrasound-guided fine
      needle aspiration of solid and lymph node lesions: any importance?
AB  - AIM: The benefits of using multiple gauge needles during EUS-FNA of solid and
      lymph node lesions are unknown. The purpose of our study was to find out the
      significance of adding a large caliber needle if small caliber needle fail to
      achieve diagnostic specimen after few passes. METHODS: It was a retrospective
      review of all EUS-FNA procedures performed by one of the two experienced
      endosonographers. A large (22 or 19 gauge) needle was added if on-site cytologic
      analysis did not reveal adequate specimen after >=2 passes. The adequacy of the
      specimen was determined by the Cytopathologist, and categorized as either
      satisfactory for analysis or unsatisfactory. The cytologic findings were reported
      as either benign or malignant. RESULTS: Out of total 1200 EUS cases, FNA was
      performed in 306 cases with different solid and lymph node lesions. Multiple
      gauge needles were used in 188/306 (39%) cases. There was no statistically
      significant difference in the diagnostic yield and definitive diagnosis between
      multiple and single gauge needle groups. The finding was unchanged after
      controlling the number of needle passes. No complications were noted. CONCLUSION:
      The addition of a large caliber needle achieved at least the same (or even
      slightly higher diagnostic yield), and can be a method of rescue in certain
      cases.

PMID- 23867952
TI  - Digital sampling, bits, and psychophysiological data: a primer, with cautions.
AB  - The assumption that technical terms used in psychophysiology literature are
      somehow understood via previous explanations in the literature is tenuous at
      best. While improved software has made the use of encoders (the "black box") more
      user friendly, it cannot replace a basic understanding as to how, what, when and
      why the encoder collects data. Further, with the improved software it is now
      easier to produce a column of data and make erroneous interpretations if one is
      not careful or does not have the requisite background knowledge. Once completed,
      it can be very difficult to go back and identify where the error(s) was made. In
      this primer, analog and digital processing, sampling, bandwidth, and bits are
      interpreted through every day events to illustrate the reasons for concern. 

PMID- 23867953
TI  - Analysis of trypsin inhibition activity in human plasma proteins after separation
      by non-denaturing two-dimensional electrophoresis.
AB  - BACKGROUND: The functions of proteins can be retained following separation by non
      denaturing two-dimensional electrophoresis (2-DE). The trypsin inhibition
      activities can then be examined following the separation and immobilization of
      the proteins under non-denaturing conditions. METHODS: Human plasma proteins were
      separated using 2-DE and transferred onto a polyvinylidene difluoride membrane
      and stained using Ponceau S. The trypsin inhibition activity of the membrane
      bound proteins was qualitatively examined using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. The activities were also
      quantitatively examined by analyzing the release of the azo-chromophore when
      azocasein was the substrate. RESULTS: Trypsin activity was inhibited by the
      haptoglobin and alpha2-macroglobulin spots located on the membrane, whereas the
      protease activity was retained for the spots containing albumin and transferrin.
      The inhibition activities of the alpha2-macroglobulin and haptoglobin spots were
      4.81- and 4.83-fold higher, respectively, when compared with the inhibition
      activity of the albumin spot. An axis of the relative activities of trypsin
      inhibition was added to the 2-DE pattern of human plasma proteins to construct a
      non-denaturing 3-D map of human plasma proteins. CONCLUSION: This 3-D map should
      represent a suitable diagnostic tool for the qualitative and quantitative
      analyses of the trypsin inhibition activities of proteins.

PMID- 23867956
TI  - Influence of genetic polymorphisms on biomarkers of exposure and effects in
      children living in Upper Silesia.
AB  - This article is a follow-up to our previous molecular epidemiology studies on the
      DNA damage in children from the Upper Silesia region of Poland. It is expected
      that metabolic and DNA repair gene polymorphisms may modulate individual
      susceptibility to environmental exposure. In this study, we investigate the
      association between polymorphisms of metabolising (CYP2D, EPHX1, GSTM1, GSTP1,
      GSTT1, NAT2) and DNA repair (XPD, XRCC1, XRCC3) genes and selected biomarkers of
      exposure and effect such as levels of 1-hydroxypyrene (1-OHP) and urinary
      mutagenicity, aromatic DNA adducts, sister chromatid exchange (SCE) and
      micronuclei (MN) in 74 children. Both 1-OHP concentration and urinary
      mutagenicity tested by TA98+S9 were significantly higher in individuals with
      EPHX1 (exon 4) Arg/Arg genotype than in individuals with other genotype. The
      EPHX1 (exon 3) significantly affected urinary mutagenicity tested with strain
      YG1024+S9. The urinary mutagenicity in individuals with Tyr/Tyr homozygotes was
      lower than in individuals with Tyr/His and His/His (1057+/-685 vs. 1432+/-1003
      revertants/mol creatinine). XRCC3 Met/Met genotype was associated with
      significantly higher levels of 1-OHP in urine compared with only The/Met
      genotype. The PAH-DNA adduct levels in the subgroup with GSTM1 null genotype was
      2-fold higher than in individuals with GSTM1 active (7.06+/-5.12 vs. 13.14+/-9.81
      adduct/10(8) nucleotides). The mean level of aromatic DNA adducts in children
      with deletion of the GSTT1 gene was significantly higher compared with
      individuals with that gene present (8.03+/-6.23 vs. 14.66+/-10.70 adduct/10(8)
      nucleotides). Also the carriers of the XPD Lys/Lys genotype showed higher levels
      of DNA adducts than heterozygotes (13.16+/-9.70 vs. 6.81+/-5.86 adducts/10(8)
      nucleotides). Children carrying the XRCC3-241 Met/Met genotype exhibited a higher
      number of SCE in peripheral blood lymphocytes than carriers of Thr/Met allele
      (8.15+/-0.86 vs. 7.62+/-0.79 SCE/cell). It was also observed that children with
      the GSTP1 slow conjugator had significantly elevated MN in peripheral blood
      lymphocytes compared with fast conjugator (4.23+/-3.49 vs. 6.56+/-5.00 MN/1000
      cells). 

PMID- 23867958
TI  - Impact of early surfactant and inhaled nitric oxide therapies on outcomes in
      term/late preterm neonates with moderate hypoxic respiratory failure.
AB  - OBJECTIVE: We conducted a post-hoc analysis of early inhaled nitric oxide (iNO)
      randomized controlled trial data to identify associations pertinent to the
      management of moderate hypoxic respiratory failure in term/late preterm infants.
      STUDY DESIGN: Univariate and multivariate logistic regression analyses were used
      to determine risk factors for the progression of respiratory failure and
      extracorporeal membrane oxygenation (ECMO)/death. RESULT: Among the 299 enrolled
      infants, oxygenation index (OI) <20 at enrollment (odds ratio 0.52, confidence
      interval (CI) 0.27 to 0.97) and surfactant use before randomization (odds ratio
      0.47, CI 0.24 to 0.91) were associated with decreased ECMO/death rates. Early
      surfactant use for respiratory distress syndrome, perinatal aspiration syndrome
      and pneumonia/sepsis was associated with lower risk of ECMO/death (P<0.001).
      Early iNO (OI 15 to 25) decreased the progression of respiratory failure to OI
      >30 (P=0.002) and to composite outcome of OI >30 or ECMO/death (P=0.02).
      CONCLUSION: This post-hoc analysis suggests that early use of surfactant and iNO
      in moderate respiratory failure is associated with improved outcomes.

PMID- 23867959
TI  - Toll-like receptor genetic variants are associated with Gram-negative infections
      in VLBW infants.
AB  - OBJECTIVE: To test the hypothesis that single-nucleotide polymorphisms (SNPs) in
      Toll-like receptor (TLR) genes alter susceptibility to bacterial infections and
      modulate white blood cell (WBC) counts during infections in very low birth weight
      (VLBW) infants (birth weight <1500 g). STUDY DESIGN: VLBW infants recruited in a
      multicenter study were genotyped for nine functional TLR SNPs and associations
      between SNPs and infection rates examined. WBC counts obtained during infections
      were compared among infants with and without SNPs. RESULT: In our cohort (n=408),
      90 infants developed bacterial infections. Presence of TLR4 (rs4986790 and
      rs4986791) variants were associated with Gram-negative (G-ve) infections. Female
      infants heterozygous for the X-linked IRAK1 (rs1059703) SNP had less G-ve
      infections. In regression models controlling for confounders, the TLR4
      (rs4986790) SNP was associated with increased G-ve infections. The TLR5
      (rs5744105) variant was associated with elevated WBC counts during infections.
      CONCLUSION: TLR genetic variants can contribute to increased risk of bacterial
      infections and altered immune responses in VLBW infants.

PMID- 23867957
TI  - Behavioral and socioemotional competence problems of extremely low birth weight
      children.
AB  - OBJECTIVE: To examine behavioral and social-emotional problems in extremely low
      birth weight (ELBW) children and to assess factors associated with behavioral and
      social competency outcomes at 30 to 36 months adjusted age. STUDY DESIGN: A total
      of 696 ELBW (401 to 1000 g) children from the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development Neonatal Research Network were
      included. Behavioral and social-emotional problems were assessed using the Brief
      Infant-Toddler Social and Emotional Assessment administered to parents.
      Unadjusted comparisons were performed between children with or without behavioral
      or social-emotional problems. Logistic regression was used to examine factors
      associated with behavioral outcomes. RESULT: Parents reported behavioral problems
      in 46.8%, deficits in social-emotional competence in 20.4% and having both
      behavioral and social-emotional competence problems in 15.4% of ELBW children.
      Characteristics associated with behavioral problems in logistic regression
      included female gender, lower household income and a Bayley Psychomotor
      Developmental Index (PDI)<70. Deficits in social competence were associated with
      Bayley Mental Developmental Index (MDI) and PDI scores<70 and Hispanic or Other
      races compared with White non-Hispanic. CONCLUSION: Half of the (51.9%) ELBW
      children showed behavioral or social-emotional competence problems at 30 months.
      Low socioeconomic status and low Bayley MDI and PDI scores were associated with
      behavioral and socioemotional difficulties.

PMID- 23867960
TI  - The effects of umbilical cord milking in extremely preterm infants: a randomized
      controlled trial.
AB  - OBJECTIVE: Delayed cord clamping has been shown to decrease the need for
      transfusion in preterm neonates, but may delay resuscitation. The aim of this
      study was to determine whether umbilical cord milking compared with immediate
      cord clamping in extremely preterm deliveries reduces the need for neonatal red
      blood cell transfusion. STUDY DESIGN: Women admitted to a tertiary care center
      and expected to deliver between 24 to 28 completed weeks of gestation were
      randomized to cord milking before clamping or immediate cord clamping. The
      primary outcome was the risk of neonatal transfusion, reported as risk ratio (RR)
      and 95% confidence interval (CI). RESULT: Of 113 women who were enrolled and
      randomized, 56 were assigned to cord milking with 36 remaining eligible and
      completing the study and 57 were assigned to the control group with 39 remaining
      eligible and completing the study. Albeit not statistically significant, neonates
      in the cord milking group were less likely to require transfusion compared with
      those in the control group (RR: 0.86; 95% CI: 0.73 to 1.0). Neonates whose cords
      were milked had higher hematocrits at birth (P=0.004) and were less likely to
      develop an intraventricular hemorrhage (P=0.0195). CONCLUSION: Milking the
      umbilical cord of a preterm neonate is an easy intervention with the potential to
      improve perinatal outcomes. Our results suggest that milking of the cord
      increases the neonate's initial hematocrit and may lessen the need for
      transfusion in the neonatal period. The observed reduction in the incidence of
      intraventricular hemorrhage may have important long-term implications that
      warrant further study.

PMID- 23867962
TI  - Brain wave maturation and neurodevelopmental outcome in extremely low gestational
      age neonates.
AB  - OBJECTIVE: Infants born at extremely low gestational ages are at high risk for
      developmental impairments. Early predictors of these impairments are useful for
      both clinicians and researchers. Our objective was to assess the correlation
      between the rate of brain wave maturation as measured by serial amplitude
      integrated electroencephalograms (aEEGs) and scores on standardized measures of
      infant development in extremely low gestational age neonates. STUDY DESIGN: This
      was a prospective observational study of 65 infants born before 28 weeks'
      gestational age who were assessed with an aEEG monthly between 28 and 36 weeks'
      postmenstrual age and with the Bayley Scales of Infant and Toddler Development
      III at 18 to 22 months adjusted age. We analyzed the correlation between the rate
      of brain wave maturation on aEEG and Bayley Scales of Infant and Toddler
      Development-III Cognitive and Motor Scales. RESULT: The mean rate of brain wave
      maturation was 0.83 (+/-0.36) points per week. Brain wave maturation was not
      correlated with either the Cognitive or Motor Scale (adjusted regression
      coefficients for Cognitive and Motor Scales were 1.61 (s.e.: 4.20; P=0.70) and
      2.39 (s.e.: 4.62; P=0.61), respectively. CONCLUSION: Among extremely preterm
      infants, the rate of maturational changes in brain wave characteristics between
      28 and 36 weeks' postmenstrual age is not predictive of developmental abilities
      at 18 to 22 months adjusted age.

PMID- 23867961
TI  - Maternal IgG avidity, IgM and ultrasound abnormalities: combined method to detect
      congenital cytomegalovirus infection with sequelae.
AB  - OBJECTIVE: We used maternal immunoglobulin M (IgM), immunoglobulin G (IgG)
      avidity index (AI) and fetal ultrasonography (US) to effectively detect a
      congenital cytomegalovirus-infected fetus that would suffer neurological sequelae
      after birth. STUDY DESIGN: The detecting method was prospectively adapted to 1163
      unselected pregnant women. IgM, IgG and IgG-AI were measured at the first
      prenatal examination (10.8+/-2.2 weeks of gestation). Advanced US was performed
      for the IgM-positive women at our center. The urine of 1163 neonates was examined
      via PCR. All infected neonates were followed for neurological development.
      RESULT: Most women (83.3%) were seropositive. Among them, 40 (4.1%) were IgM
      positive. Nine of forty (22.5%) had low AI, of which one showed abnormal US and
      suffered severe sequelae. The remaining eight had a normal US; however, one
      infant had hearing impairment. There were another three infected infants with
      normal development. Their mothers' serological results were: IgM positive with
      high AI (n=1); IgG positive; IgM negative with high AI (n=1); and both IgG and
      IgM negative (n=1). CONCLUSION: This method enabled us to detect infected fetuses
      having severe sequelae. However, the problem remains of detecting infected
      fetuses that only have a hearing impairment.

PMID- 23867963
TI  - Use of a genealogical database demonstrates heritability of pulmonary fibrosis.
AB  - BACKGROUND: Pulmonary fibrosis (PF) is a progressive fatal disease of unknown
      etiology. Identification of risk genes and pathways will enhance our
      understanding of this disease. Analysis of Utah genealogical resources has shown
      previously strong evidence for a genetic contribution to other disease, such as
      cancer. This approach has led to gene discovery in diseases, such as breast
      cancer and colon cancer and is used here for PF to quantify the heritability.
      HYPOTHESIS: We hypothesize that there is a heritable contribution to death from
      PF and use existing genealogic and death certificate data to examine patterns of
      relatedness amongst individuals who have died of PF. METHODS: We analyzed
      familial clustering of individuals who died from PF using the Utah Population
      Database, a unique population-based genealogical resource that has been linked to
      death certificates dating from 1904. We identified 1,000 individuals with at
      least three generations of genealogy data and a cause of death documented as PF
      (cases). We estimated the relative risk (RR) of death from PF among the first-,
      second-, and third-degree relatives of cases. We also tested the hypothesis of
      excess relatedness among the cases by comparing the average pairwise relatedness
      of all cases to the average pair-wise relatedness of 1,000 sets of matched
      controls. RESULTS: We observed significantly increased risk for death from PF
      among the first- (RR = 4.69), second- (RR = 1.92), and third-degree relatives (RR
      = 1.14) of cases. The average relatedness of the 1,000 cases was significantly
      higher than the expected average relatedness of matched control sets (p < 0.001).
      When close (first- and second-degree) relationships were ignored, significantly
      increased relatedness remained (p = 0.002). CONCLUSIONS: Our results demonstrate
      significant clustering among both close and distant relatives, providing strong
      support for genetic contributions to death from PF. High-risk pedigrees derived
      from this unique resource may help identify new risk genes and gene pathways.

PMID- 23867964
TI  - Immune diffuse alveolar hemorrhage: a retrospective assessment of a diagnostic
      scale.
AB  - BACKGROUND: Initiating early steroid treatment in patients with immune diffuse
      alveolar hemorrhage (DAH) is a key aspect of early management. However, steroid
      initiation is often delayed until the results of immunological markers and/or
      tissue biopsy have been obtained, which could contribute to poor outcomes. We
      previously developed a clinical score allowing for the early diagnosis of DAH of
      immune causes. However, this score has not been validated in an independent
      cohort of patients. The aim of this study was to assess the validity of this
      diagnostic score using an independent cohort of patients admitted for DAH of
      immune and nonimmune causes. METHODS: We conducted a retrospective cohort study
      of patients admitted between January 2002 and December 2009 for DAH of immune and
      nonimmune causes. RESULTS: Forty-six patients were included in the study, with 12
      patients having immune DAH and 34 patients with nonimmune DAH. Application of our
      previously validated clinical scale of immune DAH to this independent population
      of patients yielded an area under the ROC curve of 0.95 [0.90-1.01]. A score
      >=4/10 was associated with the best performances of this scale: sensitivity =
      1.00 [0.73-1.00], specificity = 0.88 [0.72-0.97], positive predictive value =
      0.75 [0.48-0.93], and negative predictive value = 1.00 [0.88-1.00]. CONCLUSION:
      While immunological tests and tissue biopsy results are pending, deciding whether
      to initiate an immunosuppressive treatment is challenging. The initiation of
      early corticosteroid treatment is warranted in patients with immune DAH and could
      improve outcomes. This study confirms that this score allows for a good
      discrimination between patients with immune and nonimmune DAH. Because this
      series has several limitations, including its single-center and retrospective
      nature, the small number of patients included, and the lack of therapeutic
      intervention, a prospective evaluation of this score is warranted to ascertain
      whether it can improve the adequacy of early treatment strategies and thus
      improve the outcomes of DAH patients.

PMID- 23867965
TI  - Ages and Stages Questionnaires-3 developmental screening of infants and young
      children with cancer.
AB  - The Ages and Stages Questionnaires-3(r) (ASQ-3) for developmental screening in
      our young oncology patients was pilot tested in children 4 to 48 months of age
      with newly diagnosed cancer. Subjects were screened within 28 days of diagnosis
      (baseline), at 6 and 12 months. Twenty-six of 30 enrolled parents (87%) completed
      all 3 screens. Screens were completed by parents within 15 minutes. ASQ-3
      screening identified unsuspected developmental delays as follows: 7 at baseline,
      4 at 6 months, and 3 at 12 months. ASQ-3 developmental screening is feasible,
      identifies early developmental delays in young children with cancer, and helps
      initiate appropriate referrals. 

PMID- 23867966
TI  - Screening for pain in pediatric brain tumor survivors using the pain thermometer.
AB  - Numerous instruments have been developed to measure pain within various
      populations; however, there remains limited understanding of how these tools are
      applicable to childhood cancer survivors. This study compared a single-item
      screening measure, the Pain Thermometer (PT), with a more in-depth measure, the
      Brief Pain Survey (BPS), in a cohort of childhood brain tumor survivors. Ninety
      nine survivors (aged 13-32 years) with a median time from diagnosis of 9.9 years
      (range = 2-18 years) completed the 2 instruments. Thirty-seven survivors (37.4%)
      were identified on the BPS as having clinically significant pain, but the PT was
      not found to be an accurate tool for identifying these pain cases. Application of
      receiver operating characteristic curve analysis of PT ratings against BPS
      criterion indicated overall concordance between measures. No cutoff score on the
      PT were identified that resulted in acceptable sensitivity, meaning pain cases
      identified on the BPS would be missed on the PT. Findings suggest that a multi
      item screening measure may better identify clinically significant pain in
      childhood brain tumor survivors compared with a 1-item screening measure alone. 

PMID- 23867967
TI  - Coupling of narrow and wide band-gap semiconductors on uniform films active in
      bacterial disinfection under low intensity visible light: implications of the
      interfacial charge transfer (IFCT).
AB  - This study reports the design, preparation, testing and surface characterization
      of uniform films deposited by sputtering Ag and Ta on non-heat resistant
      polyester to evaluate the Escherichia coli inactivation by TaON, TaN/Ag, Ag and
      TaON/Ag polyester. Co-sputtering for 120 s Ta and Ag in the presence of N2 and O2
      led to the faster E. coli inactivation by a TaON/Ag sample within ~40 min under
      visible light irradiation. The deconvolution of TaON/Ag peaks obtained by X-ray
      photoelectron spectroscopy (XPS) allowed the assignment of the Ta2O5 and Ag
      species. The shifts observed for the XPS peaks have been assigned to AgO to Ag2O
      and Ag(0), and are a function of the applied sputtering times. The mechanism of
      interfacial charge transfer (IFCT) from the Ag2O conduction band (cb) to the
      lower laying Ta2O5 (cb) is discussed suggesting a reaction mechanism. The optical
      absorption of the TaON and TaON/Ag samples found by diffuse reflectance
      spectroscopy (DRS) correlated well with the kinetics of E. coli inactivation. The
      TaON/Ag sample microstructure was characterized by contact angle (CA) and by
      atomic force microscopy (AFM). Self-cleaning of the TaON/Ag polyester after each
      disinfection cycle enabled repetitive E. coli inactivation.

PMID- 23867968
TI  - Mechanistic antimicrobial approach of extracellularly synthesized silver
      nanoparticles against gram positive and gram negative bacteria.
AB  - The development of eco-friendly and reliable processes for the synthesis of
      nanoparticles has attracted considerable interest in nanotechnology. In this
      study, an extracellular enzyme system of a newly isolated microorganism,
      Exiguobacterium sp. KNU1, was used for the reduction of AgNO3 solutions to silver
      nanoparticles (AgNPs). The extracellularly biosynthesized AgNPs were
      characterized by UV-vis spectroscopy, Fourier transform infra-red spectroscopy
      and transmission electron microscopy. The AgNPs were approximately 30 nm (range 5
      50 nm) in size, well-dispersed and spherical. The AgNPs were evaluated for their
      antimicrobial effects on different gram negative and gram positive bacteria using
      the minimum inhibitory concentration method. Reasonable antimicrobial activity
      against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli and
      Staphylococcus aureus was observed. The morphological changes occurred in all the
      microorganisms tested. In particular, E. coli exhibited DNA fragmentation after
      being treated with the AgNPs. Finally, the mechanism for their bactericidal
      activity was proposed according to the results of scanning electron microscopy
      and single cell gel electrophoresis.

PMID- 23867969
TI  - Preparation, formation mechanism and photocatalysis of ultrathin mesoporous
      single-crystal-like CeO2 nanosheets.
AB  - For the first time we synthesized mesoporous CeO2 nanosheets with single-crystal
      like, ultrathin and uniform-sized structures through the thermal decomposition of
      specially prepared intermediates of Ce(OH)CO3 nanosheets. The resulting single
      crystal-like CeO2 porous nanosheets are only 2.4 nm thick, as measured by AFM.
      BET analysis indicated that the pores of the nanosheets were centered at 3.7 nm.
      A novel structure transformation mechanism from 1D to 0D, then to a 2D assembly
      was clearly revealed. Moreover, such ultrathin CeO2 porous nanosheets exhibited
      much higher photocatalytic activity for dye degradation than that of
      polycrystalline CeO2 nanoparticles. 

PMID- 23867970
TI  - Aqueous synthesis of glutathione-coated PbS quantum dots with tunable emission
      for non-invasive fluorescence imaging in the second near-infrared biological
      window (1000-1400 nm).
AB  - Glutathione-coated PbS quantum dots with tunable emission were synthesized in the
      aqueous phase and used for non-invasive tissue imaging in the second near
      infrared biological window. 

PMID- 23867971
TI  - miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical
      cancer.
AB  - BACKGROUND/AIMS: MicroRNA (miRNA) plays important roles in the development of
      different cancers. In this study, we investigated the roles and mechanisms of miR
      203 in human cervical cancer. METHODS: miR-203 expression was detected in
      cervical cancer tumors and cell lines by qRT-PCR. The methylation status in the
      promoter region of miR-203 was examined by methylation-specific PCR. The
      functional effect of miR-203 was determined by both in vitro and in vivo assays.
      RESULTS: miR-203 was frequently down-regulated in cervical cancer tumors and cell
      lines. This down-regulation of miR-203 was associated with methylation of the miR
      203 promoter. Furthermore, miR-203 down-regulated vascular endothelial growth
      factor alpha (VEGFA) expression by directly targeting its 3'-untranslated region.
      Functional assays revealed that miR-203 suppressed cervical cancer cell
      proliferation, tumor growth, and angiogenesis in nude mice, whereas forced
      expression of VEGFA rescued this inhibitory effect. CONCLUSION: Our collective
      findings indicate that miR-203 functions as a tumor suppressor by targeting
      VEGFA, resulting in the inhibition of tumor growth and angiogenesis. Thus, miR
      203 may be a potential therapeutic target and prognostic marker in cervical
      cancer.

PMID- 23867973
TI  - Robotic repair of vesico-vaginal fistula with perisigmoid fat flap interposition:
      state of the art for a challenging case?
AB  - Since its introduction, robotic-assisted operations have established themselves
      in an increasingly wide range of procedures. We applied this approach as a viable
      surgical alternative for the management of a complex vesicovaginal fistula. We
      present the case of a patient with total urinary incontinence due to the
      formation of a vesicovaginal fistula, following total abdominal hysterectomy. The
      fistula was located at the vaginal vault and at approximately one cm from the
      right ureteric orifice. For this specific scenario a robotic approach was chosen
      over the vaginal-, laparotomic- and laparoscopic repair, as in our view it
      offered the best possibility to specifically treat the target anatomy with a
      reduced risk for involvement of the surrounding structures, while maintaining a
      low morbidity and a quick postoperative recovery.In our video we show how the
      vesicovaginal fistula can be repaired by interposition of a vascularized flap of
      perisigmoid fat, in order to reduce the risk of recurrences [Ezzat et al., Repair
      of giant vesicovaginal fistulas, 181(3):1184-1188, 2009].The postoperative course
      was uneventful; on postoperative day 1 the patient reported pain of 2/10 on a VAS
      scale (0 = no pain; 10 = unbearable pain) and was mobilized. She was discharged
      on postoperative day two with bladder catheter in situ. The successful repair of
      the fistulous tract was confirmed via retrograde cystogram on postoperative day
      10 and the patient was continent immediately after catheter removal. At the six
      month follow up visit the patient had no complaints. 

PMID- 23867972
TI  - Presence of a neo-epitope and absence of amyloid beta and tau protein in
      degenerative hippocampal granules of aged mice.
AB  - Clustered pathological granules related to a degenerative process appear and
      increase progressively with age in the hippocampus of numerous mouse strains. We
      describe herein the presence of a neo-epitope of carbohydrate nature in these
      granules, which is not present in other brain areas and thus constitutes a new
      marker of these degenerative structures. We also found that this epitope is
      recognised by a contaminant IgM present in several antibodies obtained from mouse
      ascites and from both mouse and rabbit sera. These findings entail the need to
      revise the high number of components that are thought to be present in the
      granules, such as the controversial beta-amyloid peptides described in the
      granules of senescence-accelerated mouse prone-8 (SAMP8) mice. Characterisation
      of the composition of SAMP8 granules, taking into account the presence of the neo
      epitope and the contaminant IgM, showed that granules do not contain either beta
      amyloid peptides or tau protein. The presence of the neo-epitope in the granules
      but not in other brain areas opens up a new direction in the study of the
      neurodegenerative processes associated with age. The SAMP8 strain, in which the
      progression of the granules is enhanced, may be a useful model for this purpose. 

PMID- 23867974
TI  - Jaspers, the body, and schizophrenia: the bodily self.
AB  - Karl Jaspers laid the foundations of contemporary psychopathology. Among Jaspers'
      contributions was his powerful vision of psychiatry as a crucial way to shed
      light on the human condition and existence by integrating the scientific study of
      psychic diseases with a theoretical approach focused on human experience. This
      perspective should be revitalized. In the present paper we start from the role
      Jaspers assigns to the body when discussing the notion of 'personalization'. We
      explore the relationship between a minimal notion of the self, the 'bodily self',
      and its potentiality for movement - the self's 'power for action'. Based on
      recent empirical evidence, we then propose a connection between the implicit
      bodily self-experience and important psychopathological aspects of schizophrenia
      by showing that schizophrenic patients exhibit a disruption of implicit bodily
      self-knowledge. We propose that the bodily nature of the implicitly experiencing
      self might enable the continuum of experience along which all visions of the
      world are located - both in healthy and psychotic individuals. The power for
      action might provide the possibility to give form to the bodily presence
      characterizing in the first place our being selves.

PMID- 23867975
TI  - The 6-minute walk test and person-reported outcomes in boys with duchenne
      muscular dystrophy and typically developing controls: longitudinal comparisons
      and clinically-meaningful changes over one year.
AB  - INTRODUCTION: Data is currently lacking anchoring a 30-meter longitudinal change
      in walking ability by 6-minute walk test (6MWT) in Duchenne muscular dystrophy as
      a minimal clinically important difference and "clinically meaningful" person
      reported outcomes (PROs) at differing levels of ambulatory ability. METHODS: We
      describe correlation between measures, 1-year change in measures, and correlation
      of 1-year changes between measures for the six-minute walk test (6MWT), 10-meter
      run/walk velocity, PedsQL and POSNA Pediatric Outcomes Data Collection Instrument
      (PODCI) in 24 4-12 year old. ambulatory DMD and 36 typical controls, and
      determine if minimal clinically important differences (MCID) of PROs contribute
      to different estimates of 6-minute walk distance (6MWD) change at differing
      levels of ability. RESULTS: PedsQL total and physical function and PODCI global,
      transfer/mobility and sports/physical function PROs demonstrated significant
      differences between DMD and controls (p<0.00001). In DMD, 6MWD and 10-meter
      run/walk velocity were correlated with PODCI domain scores, with the
      transfer/mobility scale showing the strongest relationship (r=0.79 and r=0.76).
      In DMD, 6MWD distance and 10-meter run/walk velocity weakly correlated with
      PedsQL domain scores. In DMD, 6MWD, 10-meter run/walk velocity, and PODCI global
      and transfer and basic mobility demonstrated significant one-year change and
      exceeded the amount of change representing MCID. In DMD, 6MWD change highly
      correlated with change in PODCI global and PODCI transfer/mobility scores (r=0.76
      and r=0.93). PODCI global and PODCI transfer/mobility scales provided the best
      estimates of 6MWT performance. A "meaningful" 4.5 point change in a low PODCI
      transfer / basic mobility score of 30 to 34.5 was associated with a 5.6m 6MWD
      change from 150.3 to 155.9m. At PODCI levels closer to normative levels for
      healthy controls, the change in 6MWD distance associated with a "meaningful"
      change in PODCI scores was almost 46m. DISCUSSION: At lower levels of function,
      smaller increases in 6MWD result in meaningful change in quality of life (QoL)
      instrument scores. At higher levels of function, larger increases may be
      necessary to achieve the same QoL change score.

PMID- 23867976
TI  - The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS):
      Utility in detection and characterization of mild cognitive impairment due to
      Alzheimer's disease.
AB  - Current diagnostic criteria for mild cognitive impairment (MCI) due to
      Alzheimer's disease (AD) require standardized tests that are capable of measuring
      a range of neurocognitive abilities in healthy elderly individuals and sensitive
      to detect change over time. There currently is no clearly-established "gold
      standard" for this purpose. The Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) is a widely used neuropsychological test
      battery for the clinical diagnosis/tracking of dementia also recently
      incorporated into clinical trials of new investigational medications for AD
      treatment. The RBANS has a number of design features that suggest possible
      utility in diagnosis/tracking of MCI. Eighty-one patients with MCI completed the
      RBANS and their scores were compared with 81 demographically matched healthy
      controls. RBANS Total Scale scores in both groups were normally distributed,
      demonstrating no floor/ceiling effects. The MCI group was most impaired on the
      Delayed Memory Index (DMI). Receiver operating characteristic analyses reflected
      good discrimination, with an area under the curve of 0.88 for the Total Scale
      score and 0.90 for the DMI score. The profile of performance for the MCI group
      was similar to that previously reported for mild AD patients. The RBANS may be a
      suitable neurocognitive battery for the detection and tracking of MCI presumed to
      be due to AD.

PMID- 23867977
TI  - Nanocomposite liposomes containing quantum dots and anticancer drugs for
      bioimaging and therapeutic delivery: a comparison of cationic, PEGylated and
      deformable liposomes.
AB  - Multifunctional liposomes loaded with quantum dots (QDs) and anticancer drugs
      were prepared for simultaneous bioimaging and drug delivery. Different
      formulations, including cationic, PEGylated and deformable liposomes, were
      compared for their theranostic efficiency. We had evaluated the physicochemical
      characteristics of these liposomes. The developed liposomes were examined using
      experimental platforms of cytotoxicity, cell migration, cellular uptake, in vivo
      melanoma imaging and drug accumulation in tumors. The average size of various
      nanocomposite liposomes was found to be 92-134 nm. Transmission electron
      microscopy confirmed the presence of QDs within liposomal bilayers. The
      incorporation of polyethylene glycol (PEG) and Span 20 into the liposomes greatly
      increased the fluidity of the bilayers. The liposomes provided sustained release
      of camptothecin and irinotecan. The cytotoxicity and cell migration assay
      demonstrated superior activity of cationic liposomes compared with other
      carriers. Cationic liposomes also showed a significant fluorescence signal in
      melanoma cells after internalization. The liposomes were intratumorally
      administered to a melanoma-bearing mouse. Cationic liposomes showed the brightest
      fluorescence in tumors, followed by classical liposomes. This signal could last
      for up to 24 h for cationic nanosystems. Intratumoral accumulation of
      camptothecin from free control was 35 nmol g(-1); it could be increased to 50
      nmol g(-1) after loading with cationic liposomes. However, encapsulation of
      irinotecan into liposomes did not further increase intratumoral drug
      accumulation. Cationic liposomes were preferable to other liposomes as
      nanocarriers in both bioimaging and therapeutic approaches.

PMID- 23867978
TI  - Uses and abuses of patient reported outcome measures (PROMs): potential
      iatrogenic impact of PROMs implementation and how it can be mitigated.
AB  - Having been a national advocate for the use of patient reported outcome measures
      (PROMs) in Child and Adolescent Mental Health Services (CAMHS) in the UK for the
      last decade, I have become increasingly concerned that unless the potential
      iatrogenic impact of widespread policy requirement for use of PROMs (Department
      of Health, Children and Young People's Health Outcomes Strategy, 2012) is
      recognised and addressed their real potential benefits (Sapyta et al., J Clin
      Psychol 61(2):145-153, 2005) may never be realized. Drawing on examples from
      PROMs implementation in CAMHS in the UK (Wolpert et al., J Ment Health 21(2):165
      173, 2012a; Child Adolesc Mental Health 17(3):129-130, 2012b). I suggest key ways
      forward if PROMs are to support best clinical practice rather than undermine it. 

PMID- 23867979
TI  - Direct compression of cellulose and lignin isolated by a new catalytic treatment.
AB  - Tablet compression of softwood cellulose and lignin prepared by a new catalytic
      oxidation and acid precipitation method were investigated and compared with the
      established pharmaceutical direct compression excipients. Catalytic pretreated
      softwood cellulose (CPSC) and lignin (CPSL) were isolated from pine wood (Pinus
      sylvestris). The compaction studies were carried out with an instrumented
      eccentric tablet machine. The plasticity and elasticity of the materials under
      compression were evaluated using force-displacement treatment and by determining
      characteristic plasticity (PF) and elasticity (EF) factors. With all biomaterials
      studied, the PF under compression decreased exponentially as the compression
      force increased. The compression force applied in tablet compression did not
      significantly affect the elasticity of CPSC and microcrystalline cellulose (MCC)
      while the EF values for softwood lignins increased as compression force
      increased. CPSL was clearly a less plastically deforming and less compactable
      material than the two celluloses (CPSC and MCC) and hardwood lignin. CPSL
      presented deformation and compaction behaviour almost identical to that of
      lactose monohydrate. In conclusion, the direct tablet compression behaviour of
      native lignins and celluloses can greatly differ from each other depending on the
      source and isolation method used. 

PMID- 23867980
TI  - How meaningful are heritability estimates of liability?
AB  - It is commonly acknowledged that estimates of heritability from classical twin
      studies have many potential shortcomings. Despite this, in the post-GWAS era,
      these heritability estimates have come to be a continual source of interest and
      controversy. While the heritability estimates of a quantitative trait are subject
      to a number of biases, in this article we will argue that the standard
      statistical approach to estimating the heritability of a binary trait relies on
      some additional untestable assumptions which, if violated, can lead to badly
      biased estimates. The ACE liability threshold model assumes at its heart that
      each individual has an underlying liability or propensity to acquire the binary
      trait (e.g., disease), and that this unobservable liability is multivariate
      normally distributed. We investigated a number of different scenarios violating
      this assumption such as the existence of a single causal diallelic gene and the
      existence of a dichotomous exposure. For each scenario, we found that substantial
      asymptotic biases can occur, which no increase in sample size can remove.
      Asymptotic biases as much as four times larger than the true value were observed,
      and numerous cases also showed large negative biases. Additionally, regions of
      low bias occurred for specific parameter combinations. Using simulations, we also
      investigated the situation where all of the assumptions of the ACE liability
      model are met. We found that commonly used sample sizes can lead to biased
      heritability estimates. Thus, even if we are willing to accept the meaningfulness
      of the liability construct, heritability estimates under the ACE liability
      threshold model may not accurately reflect the heritability of this construct.
      The points made in this paper should be kept in mind when considering the
      meaningfulness of a reported heritability estimate for any specific disease. 

PMID- 23867981
TI  - The Frankfort plane and head positioning in facial aesthetic analysis--the
      perpetuation of a myth.

PMID- 23867983
TI  - Ocular delivery systems for poorly soluble drugs: an in-vivo evaluation.
AB  - For highly potent but poorly water-soluble drugs like cyclosporine A, the
      development of aqueous formulations providing an increase of corneal drug tissue
      levels, and thus of bioavailability, to increase patient compliance is still a
      challenge. Therefore, we designed two water-based liquid application systems, an
      in-situ nanosuspension (INS) and a micellar solution (MS), and tested both
      formulations in vivo at the rabbit cornea for tolerability and the tissue uptake
      of CsA. The evaluation of the biological tolerability by periodical eye
      examination during 180 min and quantification in a defined grading system
      revealed that the INS evoked minimal to no irritations whereas the MS was
      perfectly tolerated. After the observation period, the rabbits were sacrificed
      and the corneal tissue levels of CsA were analyzed. The INS and the MS both
      showed high levels of 1683+/-430 ngCsA/gcornea and 826+/-163 ngCsA/gcornea,
      respectively, and exceeded drug tissue levels reported for Restasis((r)) (350
      ngCsA/gcornea) and cationic emulsions (750 ngCsA/gcornea). These results marked
      our INS and MS as outstanding novel approaches for the treatment of inflammatory
      corneal diseases.

PMID- 23867982
TI  - Tamoxifen improves cholinergically modulated cognitive performance in
      postmenopausal women.
AB  - Tamoxifen (TMX) is a selective estrogen receptor modulator that is used as an
      estrogen receptor antagonist for the treatment and prevention of breast cancer.
      Whether TMX has antagonist activities in the human brain is less clear and its
      effects on cognitive function have not been experimentally explored. This study
      examined how TMX affected cognitive performance in older women using a model of
      anticholinergic drug-induced cognitive dysfunction. Twenty-one postmenopausal
      women were administered 20 mg of oral TMX or placebo for 3 months. Participants
      then took part in five drug challenges using the anticholinergic antinicotinic
      agent mecamylamine (MECA) and antimuscarinic agent scopolamine (SCOP) and were
      tested on a comprehensive battery including tasks of attention and psychomotor
      function, verbal episodic memory, and spatial navigation. After a 3-month placebo
      washout, participants were then crossed over to the alternate treatment and
      repeated the drug challenges after 3 months. Compared with placebo treatment, TMX
      significantly attenuated the impairment from cholinergic blockade on tasks of
      verbal episodic memory and spatial navigation, but effects on
      attentional/psychomotor tasks were more variable. Analysis by APOE genotype
      showed that APO E4+ women showed a greater beneficial effect of TMX on reversing
      the cholinergic impairment than APO E4- women on most tasks. This study provides
      evidence that TMX may act as an estrogen-like agonist to enhance cholinergic
      system activity and hippocampally mediated learning.

PMID- 23867984
TI  - An ovarian cell microcapsule system simulating follicle structure for providing
      endogenous female hormones.
AB  - The aim of this study was to create a microcapsule system simulating native
      follicle structure by introducing microcarrier culture to microencapsulation for
      providing endogenous female hormones. Granulosa and theca cells of rat follicles
      were isolated. Granulosa cells were grown on microcarriers and enclosed together
      with theca cells in alginate-chitosan-alginate microcapsules. The cell viability
      and female hormone secretion were investigated in vitro. The microcapsules were
      transplanted to ovariectomized rats and the serum levels of estradiol and
      progesterone were measured for 60 days. The microencapsulated granulosa cells
      growing on microcarriers exhibited enhanced viability and promoted secreting
      ability of estradiol and progesterone compared with those without the
      microcarriers. Co-microencapsulation of granulosa cells and theca cells markedly
      elevated estradiol secretion in vitro. Transplantation of co-microencapsulated
      granulosa cells on microcarriers and theca cells maintained serum estradiol and
      progesterone at normal levels for 60 days. Microcarrier cell culture has been
      proved to be an effective method to enhance the viability of granulosa cells in
      microcapsules. Moreover, the transplantation of microcapsules enclosing granulosa
      cells on microcarriers and theca cells may be promising to provide endogenous
      female hormones for menopausal syndrome treatment. 

PMID- 23867985
TI  - I. Technological approaches to improve the dissolution behavior of nateglinide, a
      lipophilic insoluble drug: nanoparticles and co-mixing.
AB  - Nateglinide is a non-sulphonylurea insulinotropic oral antidiabetic agent. The
      main problem in formulating an oral dosage form is its low solubility in aqueous
      media. This problem is particularly critical for an anti-diabetic drug because it
      should be administered just before the meals and be quickly bioavailable to cover
      the post-prandial glycemic peak. In this work, some technological approaches have
      been studied to improve the dissolution rate of nateglinide. Furthermore, two
      different polymorphs of nateglinide (H and B) have been tested to evaluate the
      influence of the crystal habitus on the dissolution behavior of the drug. The
      results have clearly demonstrated that wettability plays a key role in the
      dissolution behavior of nateglinide. As a matter of fact the physical dispersion
      of the drug with colloidal silica or hydrophilic swellable polymers strongly
      enhances the dissolution rate of nateglinide. The two polymorphs tested did not
      show significant differences in terms of dissolution behavior. 

PMID- 23867986
TI  - In-silico simulations of advanced drug delivery systems: what will the future
      offer?
AB  - This commentary enlarges on some of the topics addressed in the Position Paper
      "Towards more effective advanced drug delivery systems" by Crommelin and Florence
      (2013). Inter alia, the role of mathematical modeling and computer-assisted
      device design is briefly addressed in the Position Paper. This emerging and
      particularly promising field is considered in more depth in this commentary. In
      fact, in-silico simulations have become of fundamental importance in numerous
      scientific and related domains, allowing for a better understanding of various
      phenomena and for facilitated device design. The development of novel prototypes
      of space shuttles, nuclear power plants and automobiles are just a few examples.
      In-silico simulations are nowadays also well established in the field of
      pharmacokinetics/pharmacodynamics (PK/PD) and have become an integral part of the
      discovery and development process of novel drug products. Since Takeru Higuchi
      published his seminal equation in 1961 the use of mathematical models for the
      analysis and optimization of drug delivery systems in vitro has also become more
      and more popular. However, applying in-silico simulations for facilitated
      optimization of advanced drug delivery systems is not yet common practice. One of
      the reasons is the gap between in vitro and in vivo (PK/PD) simulations. In the
      future it can be expected that this gap will be closed and that computer assisted
      device design will play a central role in the research on, and development of
      advanced drug delivery systems. 

PMID- 23867987
TI  - Sirolimus-loaded stealth colloidal systems attenuate neointimal hyperplasia after
      balloon injury: a comparison of phospholipid micelles and liposomes.
AB  - Restenosis after angioplasty remains a serious complication in clinical
      cardiology. This study aims to investigate the stealth colloidal systems for
      local intra-arterial drug delivery. Micelles from polyethylene glycol conjugated
      with phosphatidylethanolamine and PEGylated liposomes loaded with sirolimus were
      prepared and characterized with regard to their loading efficiency, particle size
      distribution, zeta potential, morphology, nuclear magnetic resonance
      spectroscopy, drug release profile and stability. The antirestenotic effects of
      the sirolimus-loaded micelles (14 nm) and liposomes (90 nm) were evaluated and
      compared in the rat carotid injury model following local intravascular delivery.
      In comparison to control groups, treatment of balloon injured rats with drug
      loaded micelles and nanoliposomes significantly reduced vascular stenosis by 42%
      and 19%, respectively (P<0.05). In addition, the luminal area was significantly
      enlarged by 39% and 60% following treatment with sirolimus-loaded liposomes and
      micelles, respectively (P<0.05). Immunohistochemistry revealed that sirolimus
      loaded nanocarriers suppressed cell proliferation (Ki67-positive cells) as
      compared to control groups without affecting the density of smooth muscle actin
      staining. These results suggest that both colloidal nanocarriers could serve as
      effective intramural drug delivery systems for the treatment of restenosis;
      however, phospholipid based micelles provided better antirestenotic effects than
      PEGylated liposomes.

PMID- 23867989
TI  - Effect of streptomycin on melanogenesis and antioxidant status in melanocytes.
AB  - Streptomycin is an aminoglycoside antibiotic with an antituberculosis activity
      commonly used in clinical practice due to its good antimicrobial characteristics.
      A well-known undesirable side effect of this drug is ototoxicity, which may be
      caused by overproduction of reactive oxygen species and loss of melanocytes in
      the inner ear. The aim of this study was to examine the effect of streptomycin on
      melanogenesis and antioxidant defense system in cultured normal human melanocytes
      (HEMa-LP). Streptomycin induced concentration-dependent loss in melanocytes
      viability. The value of EC50 was determined to be ~5.0 mM. It has been shown that
      streptomycin causes inhibition of tyrosinase activity and reduces melanin content
      in human melanocytes in a concentration-dependent manner. Significant changes in
      the activity of cellular antioxidant enzymes: superoxide dismutase, catalase, and
      glutathione peroxidase were also stated. The results obtained in vitro may
      explain a potential role of melanocytes and melanin in the causative mechanisms
      of aminoglycosides ototoxic effects in vivo.

PMID- 23867990
TI  - Shh signaling, negatively regulated by BMP signaling, inhibits the
      osteo/dentinogenic differentiation potentials of mesenchymal stem cells from
      apical papilla.
AB  - Mesenchymal stem cells (MSCs) derived from dental tissues show promise for use in
      tooth-related tissue regeneration, but the molecular mechanisms underlying their
      directed differentiation remain unclear, limiting their usefulness. Sonic
      Hedgehog (Shh) signaling is a major signaling pathway that regulates cell
      differentiation and osteogenesis. We found that when Shh signaling was activated
      by human recombinant SHH-N protein or by overexpression of active mutant M2
      Smoothened (SMO) in stem cells from apical papilla (SCAPs), GLI1, a key
      downstream transcription factor and a marker of Shh signaling, was upregulated.
      Subsequently, in vitro osteo/dentinogenic differentiation and in vivo
      osteogenesis were inhibited in SCAPs. Moreover, the expression of GLI1 and SMO
      were downregulated by BMP signaling while osteo/dentinogenic differentiation in
      SCAPs was upregulated. These results provide insights into the role of Shh
      signaling in the directed differentiation of MSCs derived from dental tissues and
      suggest possible target genes for optimizing the use of stem cells of dental
      origin for tissue regeneration applications.

PMID- 23867991
TI  - Histone deacetylases inhibitor trichostatin A increases the expression of
      Dleu2/miR-15a/16-1 via HDAC3 in non-small cell lung cancer.
AB  - Histone deacetylases (HDACs) inhibitor is a promising new approach to the
      treatment of lung cancer therapy via inhibiting cell growth and inducing
      apoptosis. miR-15a and miR-16-1 are important tumor suppressors through
      modulating B cell lymphoma 2 (Bcl-2), Cyclin D1, D2, and others. However, whether
      HDACs inhibitor modulates the expression of miR-15a/16-1 in lung cancer is still
      unknown. The purpose of our study was to identify a new miRNA-mediated mechanism
      which plays an important role in the anti-cancer effects of HDACs inhibitor. We
      found HDACs inhibitors trichostatin A (TSA) and sodium butyrate upregulated the
      expression of miR-15a/16-1, residing in the host tumor suppressor Dleu2 gene,
      through increasing the histone acetylation in the region of Dleu2/miR-15a/16-1
      promoter in lung cancer cells. Moreover, among class Iota HDACs subtypes, only
      knockdown of HDAC3 by specific siRNA increased the hyperacetylation of Dleu2/miR
      15a/16-1 promoter region and finally resulted in the upregulation of miR-15a/16
      1. Furthermore, overexpression of miR-15a/16-1, which were always deleted or
      downregulated in lung cancer cells, effectively suppressed cell growth and
      reduced colony formation. Finally, TSA reduced the expression of Bcl-2, an
      important survival protein in lung cancer cells, partly through upregulation of
      miR-15a/16-1. Therefore, this offers a therapeutic strategy that lung cancer
      patients who exhibit low level of miR-15a/16-1 or high activity of HDACs may
      benefit from HDACs inhibitor-based therapy.

PMID- 23867992
TI  - Ethionine regulates cell motile activity through LPA receptor-3 in liver
      epithelial WB-F344 cells.
AB  - Lysophosphatidic acid (LPA) receptors (LPA1 to LPA6) indicate a variety of
      cellular responses, such as cell proliferation, migration, differentiation, and
      morphogenesis. However, the role of each LPA receptor is not functionally
      equivalent. Ethionine, an ethyl analog of methionine, is well known to be one of
      the potent liver carcinogens in rats. In this study, to assess whether ethionine
      may regulate cell motile activity through LPA receptors, rat liver epithelial (WB
      F344) cells were treated with ethionine for 48 h. In cell motility assay with a
      cell culture insert, the treatment of ethionine at 1.0 and 10 MUM enhanced
      significantly high cell motile activity, compared with untreated cells. The
      expression levels of LPA receptor genes in cells treated with ethionine were
      measured by quantitative real time RT-PCR analysis. The expression of the Lpar3
      gene in ethionine-treated cells was significantly higher than that in untreated
      cells. Furthermore, to confirm an involvement of LPA3 on cell motility increased
      by ethionine, the Lpar3 knockdown cells were also used. The cell motile activity
      by ethionine was completely suppressed in the Lpar3 knockdown cells. These
      results suggest that LPA signaling through LPA3 may be involved in cell motile
      activity stimulated by ethionine in WB-F344 cells.

PMID- 23867993
TI  - APRIL depletion induces cell cycle arrest and apoptosis through blocking TGF
      beta1/ERK signaling pathway in human colorectal cancer cells.
AB  - It is well documented that a proliferation-inducing ligand (APRIL), a newly found
      member of tumor necrosis factor superfamily, overexpressed in the majority of
      malignancies, plays a potential role in the occurrence and development of these
      tumors. Herein, we demonstrated that APRIL depletion by using RNA interference in
      human colorectal cancer (CRC) COLO 205 and SW480 cells resulted in cell
      proliferation inhibition and evoked cell cycle arrest in G0/G1 phase and
      apoptosis, coupled with decrease in CDK2, Cyclin D1, Bcl-2 expression and an
      increase of p21 and Bax expression. In addition, the decreased expression of
      transforming growth factor-beta1 (TGF-beta1) and p-ERK was also showed in siRNA
      APRIL transfected COLO 205 and SW480 cells, whereas the protein expression levels
      of Smad2/3, p-Smad2/3, and ERK were not significantly changed. Taken together,
      our results indicate that APRIL depletion induces cell cycle arrest and apoptosis
      partly through blocking noncanonical TGF-beta1/ERK, rather than canonical TGF
      beta1/Smad2/3, signaling pathway in CRC cells. Moreover, our study highlights
      APRIL as a potential molecular target for the therapy of CRC.

PMID- 23867994
TI  - A missense mutation of the alpha-galactosidase A gene in a Chinese family of
      Fabry disease with renal failure.
AB  - BACKGROUND: Fabry disease (FD) is a rare disease due to an X-linked recessive
      inborn error of glycosphingolipid metabolism resulting from the mutations of the
      alpha-galactosidase A (alpha-gal A) gene. FD is rare in Chinese and the data on
      clinic and genetic features of FD is still limited. METHODS: In this study, the
      alpha-gal A gene of a Chinese family diagnosed with FD was analyzed for mutations
      and the genetic features of FD in this family were presented. RESULTS: The alpha
      gal A activity of the proband in this family was 0.03 nmol/ml/h in the whole
      blood. By PCR amplification and sequencing of the alpha-gal A gene exons, a
      single C-to-T transition was identified in codon 112 of exon 2. This C-to-T
      transition, mapping to position 334 in the cDNA of the alpha-gal A gene, was a
      missense mutation predicting a substitution of arginine to cysteine (p.R112C),
      which disrupts the normal activity of alpha-gal A enzyme. No further mutations
      were found in other exons of the alpha-gal A gene. In contrast to previous
      reports, in this family, all of the five male patients developed end-stage renal
      failure due to this missense mutation. CONCLUSIONS: These findings suggest that
      the missense mutation, p.R112C, in alpha-gal A gene ablates its activity and
      results in the development of FD with the renal damage.

PMID- 23867995
TI  - Sexual functioning and the effect of fatigue in traumatic brain injury.
AB  - OBJECTIVES: The primary objective was to examine specific aspects of sexual
      functioning (frequency, desired frequency, importance, and satisfaction) and
      their relationship to fatigue in individuals with traumatic brain injury (TBI)
      compared with those without brain injury. The relationship of demographic
      variables, emotional well-being, and health-related quality of life to sexual
      functioning was also explored. PARTICIPANTS: 200 community-dwelling adults with
      self-reported mild-to-severe TBI and 83 individuals without brain injury.
      MEASURES: Participation Objective, Participation Subjective, Fatigue Assessment
      Instrument, Global Fatigue Index, Beck Depression Inventory, and SF-36 Health
      Survey. METHODS: Data were collected through administration of self-report
      measures and interviews as part of a larger study of post-TBI fatigue. RESULTS:
      Several aspects of sexual activity (frequency, desired frequency, and importance)
      were closely related to specific features of fatigue among individuals with TBI.
      Women with TBI reported lower frequency and lower importance of sex than men. In
      individuals without brain injury, the impact of fatigue was limited to the
      frequency of sexual activity with no sex differences observed. CONCLUSIONS:
      Fatigue plays a different role in the subjective experience of sexual activity
      for men and women with TBI than for those without brain injuries. Fatigue and sex
      should be taken into account in future research and interventions focused on
      sexual function after TBI.

PMID- 23867996
TI  - Ethical issues in pediatric traumatic brain injury rehabilitation.

PMID- 23867997
TI  - Fatigue as a cause, not a consequence of depression and daytime sleepiness: a
      cross-lagged analysis.
AB  - OBJECTIVES: To examine the temporal relation between fatigue, depression, and
      daytime sleepiness after traumatic brain injury. Fatigue is a frequent and
      disabling consequence of traumatic brain injury (TBI). However, it is unclear
      whether fatigue is a primary consequence of the structural brain injury or a
      secondary consequence of injury-related sequelae such as depression and daytime
      sleepiness. PARTICIPANTS: Eighty-eight adults with complicated mild-severe TBI
      (69% male). MAIN MEASURES: Fatigue Severity Scale; depression subscale of the
      Hospital Anxiety and Depression Scale; Epworth Sleepiness scale at baseline and 6
      month follow-up. RESULTS: A cross-lagged path analysis computed within a
      structural equation modeling framework revealed that fatigue was predictive of
      depression (beta = .20, P < .05) and sleepiness (beta = .25, P < .05). However,
      depression and sleepiness did not predict fatigue (P > .05). CONCLUSIONS: The
      results support the view of fatigue after TBI as "primary fatigue"-that is, a
      consequence of the structural brain injury rather than a secondary consequence of
      depression or daytime sleepiness. A rehabilitation approach that assists
      individuals with brain injury in learning to cope with their neuropsychological
      and physical limitations in everyday life might attenuate their experience with
      fatigue.

PMID- 23867998
TI  - A randomised trial of weekend and evening breast screening appointments.
AB  - BACKGROUND: There is a need to research interventions that improve access to and
      convenience of breast cancer screening services. METHODS: We conducted a
      randomised trial comparing invitations to out-of-hours appointments with standard
      office hour appointments. Women who were to be invited for routine breast
      screening were randomised (3 : 1 : 1 : 1) to one of these screening invitations:
      standard office hour appointment, office hour appointment with the option to
      change to an out-of-hours appointment, weekday evening appointment, or weekend
      appointment. RESULTS: A total of 9410 women were invited to an office hour, 3519
      to an office hour with the option to change, 3271 to a weekday evening, and 3162
      to a weekend appointment. The offer of an initial out-of-hours appointment was
      associated with a non-significant decrease in attendance rates (73.7% vs 74.1%).
      The highest attendance was observed in the group offered an initial office hour
      appointment with the option to change to out-of-hours (76.1% vs 73.3% for
      standard office hour, P=0.001), with 7% of invitees exercising the option to
      change. CONCLUSION: The optimum strategy for improving attendance at breast
      screening is to offer a traditional office hour appointment and including in the
      letter of invitation an option to change to an evening or weekend appointment if
      wished.

PMID- 23867999
TI  - Deleterious BRCA1/2 mutation is an independent risk factor for carboplatin
      hypersensitivity reactions.
AB  - BACKGROUND: We tested the hypothesis that BRCA1/2 mutation carriers with ovarian
      cancer are at higher risk of carboplatin hypersensitivity reactions (HSRs).
      METHODS: Medical records of women enrolled in two carboplatin+olaparib clinical
      trials (NCT01237067/NCT01445418) were reviewed. A maximum of eight cycles
      containing carboplatin were administered. RESULTS: All women (N=87) had good
      performance status and end-organ function. Incidences of carboplatin HSR before
      enrolment and on study were 17% and 21%, respectively. Most patients who
      developed carboplatin HSR had a deleterious BRCA1/2 mutation (93%) vs 50% in
      patients without HSR (P<0.0001). Multivariable analysis accounting for potential
      confounding variables including age, history of allergies, and cumulative prior
      carboplatin cycles confirmed deleterious BRCA1/2 mutation as an independent risk
      factor for carboplatin HSR (odds ratio 13.1 (95% confidence interval 2.6-65.4),
      P=0.0017). Mutation carriers had onset of carboplatin HSR at lower cumulative
      exposure (P=0.003). No significant difference in outcome was observed on our
      study between patients with and without a history of HSR. CONCLUSION: Deleterious
      BRCA1/2 mutation increased susceptibility and shortened time to carboplatin HSR,
      independently of other reported factors. These data suggest that at-risk women
      should be counselled regarding likelihood, symptoms, and potential earlier onset
      of carboplatin HSRs.

PMID- 23868000
TI  - Expression pattern of tumour-associated antigens in hepatocellular carcinoma:
      association with immune infiltration and disease progression.
AB  - BACKGROUND: The distinct expression pattern of tumour-associated antigens (TAAs)
      might be a critical reason for the inefficacy of immunity-based treatments and
      heterogeneous postsurgical recovery in patients with solid tumours, including
      hepatocellular carcinoma (HCC). However, little is known about the clinical value
      of the coexpression patterns of multiple TAAs. METHODS: We determined the
      expression of multiple TAAs with identified immunogenicity (GPC3, AFP, SSX-2, NY
      ESO-1, EpCAM, midkine) and the density of tumour-infiltrating immune cells by
      immunohistochemistry in a panel of 362 primary HCC patients. We evaluated the
      association between the TAAs, immune cell infiltration, clinicopathological
      parameters, and prognosis. RESULTS: Patients who coexpressed more TAAs had better
      prognosis (P<0.00001, overall survival). The integrated pattern of TAA was
      associated with good differentiation and small tumour size, and with more CD57(+)
      natural killer and CD20(+) B-cell infiltration (P<0.05). Multivariate Cox
      proportional hazards analysis identified the TAA index as an independent
      prognostic indicator (hazard ratio 0.625; 95% confidence interval 0.467-0.837;
      P=0.002), and could further predict patient prognosis in collaboration with local
      immune infiltration. CONCLUSION: Our results could provide new evidence for the
      improvement of prognostic molecular signatures in HCC, and a novel rationale for
      patient enrolment in future immunotherapeutic trials and/or clinical treatments.

PMID- 23868001
TI  - Molecular sputum analysis for the diagnosis of lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality rate worldwide, mainly
      because of the presence of metastatic disease at the time of diagnosis. Early
      detection of lung cancer improves prognosis, and towards this end, large
      screening trials in high-risk individuals have been conducted since the past
      century. Despite all efforts, the need for novel (complementary) lung cancer
      diagnostic and screening methods still exists. In this review, we focus on the
      assessment of lung cancer-related biomarkers in sputum in the past decennium.
      Besides cytology, mutation and microRNA analysis, special attention has been paid
      to DNA promoter hypermethylation, of which all available literature is summarised
      without time restriction. A model is proposed to aid in the distinction between
      diagnostic and risk markers. Research on the use of sputum for non-invasive
      detection of early-stage lung cancer has brought new insights and advanced
      molecular techniques. The sputum shows a promising potential for routine
      diagnostic and possibly screening purposes. 

PMID- 23868002
TI  - Early detection of ovarian and fallopian tube cancer by examination of
      cytological samples from the endometrial cavity.
AB  - BACKGROUND: Accumulating evidence suggests that many ovarian high-grade serous
      carcinomas (HGSCs) originate in the fallopian tube. Malignant cells shed by tubal
      lesions can be detected by examination of cytological samples from the
      endometrial cavity (endometrial cytological testing). To evaluate the use of this
      method for detecting HGSC, we examined epithelial ovarian, fallopian tube, and
      primary peritoneal cancer patients. METHODS: Endometrial cytological testing was
      performed for endometrial cancer screening in asymptomatic women and for pre
      treatment evaluation in symptomatic suspected ovarian, tubal, and peritoneal
      cancer patients. RESULTS: Of the 122 ovarian, tubal, and peritoneal cancer
      patients, malignant cells were identified in 5 patients who did not show
      detectable abnormalities on imaging studies. Cervicovaginal cytology was positive
      in only one of these five patients. Four patients were asymptomatic and one was
      symptomatic. Three asymptomatic patients had early-stage HGSCs, and the other
      asymptomatic patient had positive peritoneal cytology findings but no detectable
      tumour. HGSC patients were significantly more likely to have positive findings on
      endometrial cytology than patients with other histological types (23% vs 6%,
      P=0.02). CONCLUSION: Endometrial cytological testing can detect early-stage
      ovarian, tubal, and peritoneal HGSCs without detectable pelvic masses and may be
      useful for ovarian cancer screening.

PMID- 23868003
TI  - International validation of the EORTC QLQ-ELD14 questionnaire for assessment of
      health-related quality of life elderly patients with cancer.
AB  - BACKGROUND: Older people represent the majority of cancer patients but their
      specific needs are often ignored in the development of health-related quality of
      life (HRQOL) instruments. The European Organisation for Research and Treatment of
      Cancer (EORTC) QLQ-ELD15 was developed to supplement the EORTC's core
      questionnaire, the QLQ-C30, for measuring HRQOL in patients aged >70 years in
      oncology studies. METHODS: Patients (n=518) from 10 countries completed the QLQ
      C30, QLQ-ELD15 and a debriefing interview. Eighty two clinically stable patients
      repeated the questionnaires 1 week later (test-retest analysis) and 107 others,
      with an expected change in clinical status, repeated the questionnaires 3 months
      later (response to change analysis, RCA). RESULTS: Information from the
      debriefing interview, factor analysis and item response theory analysis resulted
      in the removal of one item (QLQ-ELD15?QLQ-ELD14) and revision of the proposed
      scale structure to five scales (mobility, worries about others, future worries,
      maintaining purpose and illness burden) and two single items (joint stiffness and
      family support). Convergent validity was good. In known-group comparisons, the
      QLQ-ELD14 differentiated between patients with different disease stage, treatment
      intention, number of comorbidities, performance status and geriatric screening
      scores. Test-retest and RCA analyses were equivocal. CONCLUSION: The QLQ-ELD14 is
      a validated HRQOL questionnaire for cancer patients aged ?70 years. Changes in
      elderly patients' self-reported HRQOL may be related to both cancer evolution and
      non-clinical events.

PMID- 23868004
TI  - A phase I study of the combination of ro4929097 and cediranib in patients with
      advanced solid tumours (PJC-004/NCI 8503).
AB  - BACKGROUND: The Notch signalling pathway has been implicated in tumour
      initiation, progression, angiogenesis and development of resistance to vascular
      endothelial growth factor (VEGF) targeting, providing a rationale for the
      combination of RO4929097, a gamma-secretase inhibitor, and cediranib, a VEGF
      receptor tyrosine kinase inhibitor. METHODS: Patients received escalating doses
      of RO4929097 (on a 3 days-on and 4 days-off schedule) in combination with
      cediranib (once daily). Cycle 1 was 42 days long with RO4929097 given alone for
      the first 3 weeks followed by the co-administration of both RO4929097 and
      cediranib starting from day 22. Cycle 2 and onwards were 21 days long. Soluble
      markers of angiogenesis were measured in plasma samples. Archival tumour
      specimens were assessed for expression of three different components of Notch
      signalling pathway and genotyping. RESULTS: In total, 20 patients were treated in
      three dose levels (DLs). The recommended phase II dose was defined as 20 mg for
      RO4929097 on 3 days-on and 4 days-off schedule and 30 mg daily for cediranib. The
      most frequent treatment-related adverse events (AEs) were diarrhoea,
      hypertension, fatigue and nausea. Eleven patients had a best response of stable
      disease and one patient achieved partial response. We did not detect any
      correlation between tested biomarkers of angiogenesis or the Notch pathway and
      treatment effect. There was no correlation between mutational status and time to
      treatment failure. CONCLUSION: RO4929097 in combination with cediranib is
      generally well tolerated at the DLs tested. Preliminary evidence of antitumour
      efficacy with prolonged disease stabilisation in some patients with progressive
      malignancies warrants further clinical investigation of this treatment strategy.

PMID- 23868005
TI  - Gene expression-based prediction of myeloma cell sensitivity to histone
      deacetylase inhibitors.
AB  - BACKGROUND: Multiple myeloma (MM) is still a fatal plasma cell cancer. Novel
      compounds are currently clinically tested as a single agent in relapsing
      patients, but in best cases with partial response of a fraction of patients,
      emphasising the need to design tools predicting drug efficacy. Histone
      deacetylase inhibitors (HDACi) are anticancer agents targeting epigenetic
      regulation of gene expression and are in clinical development in MM. METHODS: To
      create a score predicting HDACi efficacy, five MM cell lines were treated with
      trichostatin A (TSA) and gene expression profiles were determined. RESULTS: The
      expression of 95 genes was found to be upregulated by TSA, using paired
      supervised analysis with Significance Analysis of Microarrays software. Thirty
      seven of these 95 genes had prognostic value for overall survival in a cohort of
      206 newly diagnosed MM patients and their prognostic information was summed up in
      a histone acetylation score (HA Score); patients with the highest HA Score had
      the shorter overall survival. It is worth noting that MM cell lines or patients'
      primary MM cells with a high HA Score had a significant higher sensitivity to
      TSA, valproic acid, panobinostat or vorinostat. CONCLUSION: In conclusion, the HA
      Score allows identification of MM patients with poor survival, who could benefit
      from HDACi treatment.

PMID- 23868006
TI  - Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III
      colorectal cancer.
AB  - BACKGROUND: The aim of our study was to evaluate the prognostic role of
      immunological microenvironnement in stage II-III CRC patients. METHODS: We
      constructed a tissue microarray from 196 consecutive patients with stage II-III
      CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARgamma
      immunoreactivity in tumour samples and their matched non-tumour tissue. We
      assessed their association with relapse-free survival (RFS; primary endpoint) and
      overall survival (OS) in multivariate Cox models. RESULTS: Low densities of CD57+
      and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes.
      A prognostic score combining CD57 (+, > vs -, <=2 cells per spot) and CD68 (+, >0
      vs -, =0 cells per spot) TIC density discriminated CRC patients at low
      (CD68+/CD57+), intermediate (CD68+/CD57-), or high (CD68-/CD57-) risk, with
      hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95%
      confidence interval (CI): 1.3-5.8) and 9.0 (3.2-25.4) for RFS, and 2.5 (1.2-5.1)
      and 10.6 (3.8-29.2) for OS, respectively, as compared with the low-risk group.
      Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk
      groups were 84% (71-91), 65% (54-74), and 12% (2-47), respectively, for RFS, and
      91% (80-96), 76% (66-84), and 25% (7-59), respectively, for OS. CONCLUSION:
      Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in
      patients with stage II-III CRC. If validated, our score based on a quick,
      inexpensive, and well-established method such as point counting on diagnostic
      tissue sections could be used routinely as a prognostic tool in CRC patients.

PMID- 23868007
TI  - Cerebellar location may predict an unfavourable prognosis in paediatric high
      grade glioma.
AB  - BACKGROUND: High-grade glioma (HGG) of the cerebellum accounts for only 5% of
      paediatric HGG. Since little is known about these tumours, the present study
      aimed at their further characterisation. METHODS: Twenty-nine paediatric patients
      with centrally reviewed cerebellar HGG were identified from the HIT-GBM/HIT-HGG
      database. Clinical and epidemiological data were compared with those of 180
      paediatric patients with cortical HGG. RESULTS: Patients with cerebellar tumours
      were younger (median age of 7.6 vs 11.7 years, P=0.028), but both groups did not
      differ significantly with regard to gender, tumour predisposing syndromes,
      secondary HGG, primary metastasis, tumour grading, extent of tumour resection,
      chemotherapy regimen, or radiotherapy. Except for an increased incidence of
      anaplastic pilocytic astrocytoma (APA) in the cerebellar subset (20.7% vs 3.3%;
      P<0.001), histological entities were similarly distributed in both groups. As
      expected, tumour grading had a prognostic relevance on survival. Compared with
      cortical HGG, overall survival in the cerebellar location was significantly worse
      (median overall survival: 0.92 +/- 0.02 vs 2.03 +/- 0.32 years; P=0.0064), and
      tumour location in the cerebellum had an independent poor prognostic significance
      as shown by Cox-regression analysis (P=0.019). CONCLUSION: High-grade glioma
      represents a group of tumours with an obviously site-specific heterogeneity
      associated with a worse survival in cerebellar location.

PMID- 23868008
TI  - Tumours with elevated levels of the Notch and Wnt pathways exhibit efficacy to PF
      03084014, a gamma-secretase inhibitor, in a preclinical colorectal explant model.
AB  - BACKGROUND: Dysregulation of the Notch pathway has been identified to play an
      important role in the development and progression of colorectal cancer (CRC). In
      this study, we used a patient-derived CRC explant model to investigate the
      efficacy of the clinical gamma-secretase inhibitor (GSI) PF-03084014. METHODS: A
      total of 16 CRC explants were treated with PF-03084014. Knockdown of RBPjkappa
      gene was used to determine the specificity of PF-03084014. Evaluation of the
      Notch and Wnt pathways in CRC explant tumours was performed by gene array and
      immunoblotting. RESULTS: We identified a subset of CRC tumours that exhibited
      elevations of the Notch and Wnt pathways sensitive to PF-03084014. Treatment with
      the GSI resulted in a significant reduction in cleaved Notch, Axin2 (Wnt
      dependent gene) and active beta-catenin. In addition, knockdown of the RBPjkappa
      gene showed that PF-03084014 has specificity for the Notch pathway in an HCT116
      cell line xenograft model. Finally, an increase in apoptosis was observed in
      CRC001- and CRC021-sensitive tumours. CONCLUSION: This study provides evidence
      that inhibition of gamma-secretase may be beneficial in a subset of patients with
      elevated levels of the Wnt and Notch pathways.

PMID- 23868009
TI  - Exposure to bisphosphonates and risk of common non-gastrointestinal cancers:
      series of nested case-control studies using two primary-care databases.
AB  - BACKGROUND: Bisphosphonates are the most commonly prescribed osteoporosis drugs
      but long-term effects are unclear, although antitumour properties are known from
      preclinical studies. METHODS: Nested case-control studies were conducted to
      investigate bisphosphonate use and risks of common non-gastrointestinal cancers
      (breast, prostate, lung, bladder, melanoma, ovarian, pancreas, uterus and
      cervical). Patients 50 years and older, diagnosed with primary cancers between
      1997 and 2011, were matched to five controls using the UK practice-based
      QResearch and Clinical Practice Research Datalink (CPRD) databases. The databases
      were analysed separately and the results combined. RESULTS: A total of 91 556 and
      88 845 cases were identified from QResearch and CPRD, respectively.
      Bisphosphonate use was associated with reduced risks of breast (odds ratio (OR):
      0.92, 95% confidence interval (CI): 0.87-0.97), prostate (OR: 0.87, 95% CI: 0.79
      0.96) and pancreatic (OR: 0.79, 95% CI: 0.68-0.93) cancers in the combined
      analyses, but no significant trends with duration. For alendronate, reduced risk
      associations were found for prostate cancer in the QResearch (OR: 0.81, 95% CI:
      0.70-0.93) and combined (OR: 0.84, 95% CI: 0.75-0.93) analyses (trend with
      duration P-values 0.009 and 0.001). There were no significant associations from
      any of the other analyses. CONCLUSION: In this series of large population-based
      case-control studies, bisphosphonate use was not associated with increased risks
      for any common non-gastrointestinal cancers.

PMID- 23868010
TI  - Feasibility trial for adjuvant chemotherapy with docetaxel plus cisplatin
      followed by single agent long-term administration of S-1 chemotherapy in patients
      with completely resected non-small cell lung cancer: Thoracic Oncology Research
      Group Study 0809.
AB  - BACKGROUND: We conducted a multicentre feasibility study for single agent long
      term S-1 chemotherapy following docetaxel plus cisplatin in patients with
      curatively resected stage II-IIIA non-small cell lung cancer. METHODS: Patients
      received three cycles of docetaxel (60 mg m(-2)) plus cisplatin (80 mg m(-2)) and
      then received S-1 (40 mg m(-2) twice daily) for 14 consecutive days with a 1-week
      rest for >6 months (maximum, 1 year). The primary end point was feasibility,
      which was defined as the proportion of patients who completed eight or more
      cycles of S-1 chemotherapy. If the lower 95% confidence interval (CI) of this
      proportion was 50% or more, then the treatment was considered as feasible. The
      sample size was set at 125 patients. RESULTS: One hundred and thirty-one patients
      were enrolled, of whom 129 patients were eligible and assessable. In all, 109
      patients (84.5%) completed 3 cycles of docetaxel plus cisplatin and 66 patients
      (51.2%, 95% CI: 42.5-59.8) completed 8 or more cycles of S-1 treatment. Grade 3/4
      toxicities during the S-1 chemotherapy included anaemia (7.3%), neutropaenia
      (3.7%), and anorexia (3.7%). CONCLUSION: The toxicity level was acceptable,
      although the results did not meet our criterion for feasibility. Modification of
      the treatment schedule for S-1 chemotherapy might improve the treatment
      compliance.

PMID- 23868011
TI  - The predictive impact of body mass index on the efficacy of extended adjuvant
      endocrine treatment with anastrozole in postmenopausal patients with breast
      cancer: an analysis of the randomised ABCSG-6a trial.
AB  - BACKGROUND: We investigated whether body mass index (BMI) can be used as a
      predictive parameter indicating patients who benefit from extended aromatase
      inhibitor (AI) treatment. METHODS: The ABCSG-6a trial re-randomised event-free
      postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to
      receive either 3 additional years of endocrine therapy using anastrozole vs nil.
      In this retrospective analysis, we investigated the prognostic and predictive
      impact of BMI on disease outcome and safety. RESULTS: In all, 634 patients (177
      normal weight, 307 overweight, and 150 obese) patients were included in this
      analysis. Normal weight patients with additional 3 years of anastrozole halved
      their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02)
      and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant
      metastases (HR 0.22; P=0.05) compared with normal weight patients without any
      further treatment. In contrast, overweight+obese patients derived no benefit from
      additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free
      survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact
      of BMI on extended endocrine treatment could be strengthened by a Cox regression
      interaction model between BMI and treatment (P=0.07). CONCLUSION: Body mass index
      may be used to predict outcome benefit of extended AI treatment in patients with
      receptor-positive breast cancer.

PMID- 23868012
TI  - Influencing surgical management in patients with carcinoma of the cervix using a
      T2- and ZOOM-diffusion-weighted endovaginal MRI technique.
AB  - BACKGROUND: Endovaginal MRI (evMRI) at 3.0-T with T2-weighted (T2-W) and ZOnal
      Oblique Multislice (ZOOM)-diffusion-weighted imaging (DWI) potentially improves
      the detection of stage Ia/Ib1 cervical cancer. We aimed to determine its
      sensitivity/specificity, document tumour-to-stromal contrast and establish the
      effect of imaging on surgical management. METHODS: Following ethical approval and
      written informed consent, 57 consecutive patients with suspected stage Ia/Ib1
      cervical cancer underwent evMRI at 3.0-T using T2-W and ZOOM-DWI.
      Sensitivity/specificity were calculated against histopathology for two
      independent observers. Tumour-to-stromal contrast was determined on T2-W, and
      diffusion-weighted (b=800 s mm(-2)) images and apparent diffusion coefficients
      (ADCs) were recorded. In patients due for radical vaginal trachelectomy (RVT),
      change of surgical management based on imaging findings was documented. RESULTS:
      Sensitivity/specificity for detecting tumour was the following: reporting read
      88.0/81.8%, anonymised read 92.0/81.8% (observer 1); 84.0/72.7% (observer2;
      median tumour volume=1.7 cm(3)). Intraobserver agreement was excellent
      (kappa=0.89) and the interobserver agreement was good (kappa=0.65). Tumour-to
      stromal contrast was greater on ZOOM-DWI compared with T2-W images (3.35+/-2.36
      vs 1.39+/-0.95; P<0.0004). Tumour and stromal ADCs were significantly different
      (P<0.00001). In 31 patients due for RVT, evMRI altered surgical management in 12
      (38.7%) cases (10 cone-biopsy, 2 chemoradiotherapy). CONCLUSION: T2-W+ZOOM-DWI
      evMRI has high sensitivity/specificity for detecting stage Ia/Ib1 cervical
      tumours; in patients due for RVT, the surgical management was altered in ~39%.

PMID- 23868013
TI  - The microRNA miR-433 promotes renal fibrosis by amplifying the TGF-beta/Smad3
      Azin1 pathway.
AB  - The TGF-beta/Smad3 pathway plays a major role in tissue fibrosis, but the precise
      mechanisms are not fully understood. Here we identified microRNA miR-433 as an
      important component of TGF-beta/Smad3-driven renal fibrosis. The miR-433 was
      upregulated following unilateral ureteral obstruction, a model of aggressive
      renal fibrosis. In vitro, overexpression of miR-433 enhanced TGF-beta1-induced
      fibrosis, whereas knockdown of miR-433 suppressed this response. Furthermore,
      Smad3, but not Smad2, bound to the miR-433 promoter to induce its expression.
      Delivery of an miR-433 knockdown plasmid to the kidney by ultrasound microbubble
      mediated gene transfer suppressed the induction and progression of fibrosis in
      the obstruction model. The antizyme inhibitor Azin1, an important regulator of
      polyamine synthesis, was identified as a target of miR-433. Overexpression of miR
      433 suppressed Azin1 expression, while, in turn, Azin1 overexpression suppressed
      TGF-beta signaling and the fibrotic response. Thus, miR-433 is an important
      component of TGF-beta/Smad3-induced renal fibrosis through the induction of a
      positive feedback loop to amplify TGF-beta/Smad3 signaling, and may be a
      potential therapeutic target in tissue fibrosis. 

PMID- 23868015
TI  - Synthesis of a neo-confused porphyrin and an unusual dihydroporphyrin derivative.
AB  - MacDonald "2 + 2" condensation of a 1,2'-dipyrrylmethane dialdehyde with a 2,2'
      dipyrrylmethane afforded a neo-confused porphyrin in 55% yield. In addition, a
      novel dihydroporphyrin with two appended pyrrolic units was isolated and
      structurally characterized. 

PMID- 23868016
TI  - Low-income cancer patients in depression treatment: dropouts and completers.
AB  - This study aims to explore reasons for depression treatment dropout among low
      income, minority women with depression and cancer. Semi-structured telephone
      interviews are conducted with 20, predominately Latina, patients who dropped out
      of depression treatment and 10 who completed. Transcripts analyzed using
      techniques rooted in grounded theory. Treatment completion barriers cluster
      according to Meichenbaum and Turk's (Facilitating treatment adherence: A
      practitioner's guidebook, Plenum Press, New York, 1987) five adherence
      dimensions: (a) Barriers to Treatment (informational, instrumental, cultural
      [language, discrimination]); (b) Disease Features (emotional burden of
      cancer/depression); (c) Cancer/Depression Treatment Regimens; (d) Provider
      Patient Relationship (depression treatment dissatisfaction); and (e) Clinical
      Setting (hospital organizational issues). Although both groups describe multiple
      overlapping dimensions of barriers, completers seem more motivated and satisfied
      with treatment, possibly due to completers experiencing the positive treatment
      effects after the first several sessions. More research should be conducted to
      determine the most effective clinical treatment methods for this population. 

PMID- 23868017
TI  - Adverse outcome pathways: hype or hope?

PMID- 23868014
TI  - Therapeutic use of traditional Chinese herbal medications for chronic kidney
      diseases.
AB  - Traditional Chinese herbal medications (TCHMs) are frequently used in conjunction
      with western pharmacotherapy for treatment of chronic kidney diseases (CKD) in
      China and many other Asian countries. The practice of traditional Chinese
      medicine is guided by cumulative empiric experience. Recent in vitro and animal
      studies have confirmed the biological activity and therapeutic effects of several
      TCHMs in CKD. However, the level of evidence supporting TCHMs is limited to
      small, nonrandomized trials. Due to variations in the prescription pattern of
      TCHMs and the need for frequent dosage adjustment, which are inherent to the
      practice of traditional Chinese medicine, it has been challenging to design and
      implement large randomized clinical trials of TCHMs. Several TCHMs are associated
      with significant adverse effects, including nephrotoxicity. However, reporting of
      adverse effects associated with TCHMs has been inadequate. To fully realize the
      therapeutic use of TCHMs in CKD, we need molecular studies to identify active
      ingredients of TCHMs and their mechanism of action, rigorous pharmacologic
      studies to determine the safety and meet regulatory standards required for
      clinical therapeutic agents, and well-designed clinical trials to provide
      evidence-based support of their safety and efficacy. 

PMID- 23868018
TI  - Memo outlining evidence for change for gender identity disorder in the DSM-5.

PMID- 23868019
TI  - Development, validation and clinical evaluation of a dried urine spot method for
      determination of hippuric acid and creatinine.
AB  - OBJECTIVES: The purpose of this study was to develop and validate a HPLC-DAD
      method for determination of creatinine and hippuric acid in dried urine spots
      (DUS), evaluating its clinical applicability. DESIGN AND METHODS: Sample
      preparation was based on a simple one step extraction with water. Analysis was
      performed in a reversed phase column Hypersil Gold C18 (150 * 4.6 mm, 3 MUm) with
      isocratic elution. Mobile phase was a mixture of triethylammonium phosphate
      buffer 5 mM, pH 3.3 and acetonitrile (90:10, v/v). RESULTS: Total analytical run
      time was 6 min. Precision assays presented CV% lower than 11.8%. Accuracy was
      96.0-103%. The lower limit of quantitation was 50 mg L(-1). Mean extraction
      yields were 99% for CR and 79.3% for HA. Analytes were stable in DUS up to 11
      days at 40  degrees C. The method was tested in 49 paired DUS and urine samples,
      with acceptable agreement. HA-CR concentration ratios in DUS were in the range of
      0.06 to 2.74, being in average 100.7% from those values found in urine.
      CONCLUSIONS: DUS samples are a useful alternative for biological monitoring of
      toluene occupational exposure, especially in Developing Countries where sample
      logistics could be an important concern.

PMID- 23868020
TI  - Characterization of estrogen response element binding proteins as biomarkers of
      breast cancer behavior.
AB  - BACKGROUND: While investigating estrogen response element (ERE) binding
      properties of human estrogen receptor-alpha (hERalpha) in breast cancer cytosols,
      other ERE-binding proteins (ERE-BP) were observed. DESIGN AND METHODS:
      Recognition properties of ERE-BP were evaluated by electrophoretic mobility shift
      assays (EMSA) with ERE sequences of the 5'-flanking region of the estrogen
      responsive gene vitellogenin A2 (VitA2). Cytosols were incubated 16 h, 4  degrees
      C with [32P]ERE sequences and separated by EMSA. A method of estimating ERE-BP
      levels was developed by measuring band intensity from EMSA profiles, expressed in
      digital light units (DLU)/MUg protein and normalized to total DLU. ERE-BP were
      purified by affinity chromatography and EMSA, and then identified by mass
      spectrometry. RESULTS: ERE-BP in cytosols did not supershift in the presence of
      anti-hERalpha or anti-hERbeta antibodies recognizing different ER epitopes
      suggesting that they are not fragments of either receptor isoform. ERE-BP
      competed with hERalpha for binding to VitA2-ERE. Increased levels of ERE-BP DNA
      binding activities measured in 310 cytosols prepared from breast cancer biopsies
      correlated with decreased patient survival. Strikingly, breast cancer patients
      with ER negative status and high ERE-BP expression exhibited the poorest disease
      free and overall survival. After purification, ERE-BP were identified as Ku70
      (XRCC6) and Ku80 (XRCC5) using mass spectrometry. ERE-BP were confirmed to be
      Ku70/80 by supershift assay. CONCLUSION: Presence of these novel ERE-binding
      proteins in a breast carcinoma is a strong predictor of poor prognosis. Our
      results suggest that ERE-BP, identified as Ku70/Ku80, in cytosols prepared from
      breast carcinoma biopsies are useful biomarkers for assessing risk of breast
      cancer recurrence.

PMID- 23868021
TI  - Valproic acid derivatives signal for apoptosis and repair in vitro.
AB  - PURPOSE: To determine the cytotoxicity of valproic acid (VPA) and its derivatives
      in human hepatoblastoma (HepG2) cells, and to study the possible toxicity of
      these compounds in human lymphocytes from patients with known hypersensitivity
      syndrome reactions (HSRs) to other medication. METHODS: Cells were exposed to
      physiological doses of VPA, valnoctamide (VCD) and its one carbon homologue sec
      Butyl-propyl-acetamide (SPD) for 2h and for 24h. Cell viability was measured
      using succinate dehydrogenase activity for hepatocytes and lymphocyte toxicity
      assay (LTA) for lymphocytes. Cytokines and apoptosis [cytokeratine 18 (cCK18
      M30)] markers were quantitated by ELISA. RESULTS: VCD and SPD presented lower
      cytotoxicity compared to VPA in cultured HepG2 cells. SPD led to cytotoxicity in
      lymphocytes. VPA and its derivatives increased the release of interferon (IFN)
      gamma and tumor necrosis factor (TNF)-alpha in media, but had no influence on the
      release of either interleukin (IL)-1 or IL-6. Significant increases in the
      release of IFN-gamma and TNF-alpha were observed in lymphocytes exposed to high
      doses of VPA, and this increased further with exposure time. SIGNIFICANCE: HepG2
      cells exposed to VCD and SPD experienced lower direct cytotoxicity than those
      treated with VPA. Lymphocytes from patients that experienced HSR to other
      medication have shown cytotoxicity to VPA and its VPA derivatives-induced. High
      levels of pro-inflammatory cytokines were released in the cell culture media,
      suggesting that inflammation plays a key role in VPA-derivatives induced
      lymphocyte toxicity.

PMID- 23868022
TI  - RAD51 gene is associated with advanced age-related macular degeneration in
      Chinese population.
AB  - OBJECTIVES: This study aims to investigate whether variations in RAD51, B3GALTL,
      TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 are associated with advanced forms of
      age-related macular degeneration (AMD) in Chinese population. DESIGN AND METHODS:
      A total of 119 Chinese patients with AMD and 99 control individuals were
      recruited. Genomic DNA was extracted from peripheral blood leukocytes. Seven
      single nucleotide polymorphisms (SNPs) from CFH, HTRA1, RAD51, B3GALTL, TNFRSF10A
      and REST-C4ORF14-POLR2B-IGFBP7 were genotyped by polymerase chain reaction (PCR)
      followed by allele-specific restriction enzyme digestion or SNaPshot. RESULTS:
      Rs10483810 in RAD51 was significantly associated with advanced AMD (P=0.045).
      Compared with the wild-type genotype GG, the odds ratio for the risk of advanced
      AMD was 4.92 (95% confidence interval: 1.04-23.36) for the heterozygous TG
      genotype. Moreover, the GT genotype at rs10483810 confers significantly increased
      risk of bilateral AMD compared to unilateral AMD (OR=12.04, 95% CI: 2.50-57.69,
      P=0.002). Rs13278062 in TNFRSF10A, rs1713985 in REST-C4ORF14-POLR2B-IGFBP7 and
      rs9542236 in B3GALTL were not found to be associated with AMD (all P>0.05).
      CONCLUSION: Our data suggested that the risk allele T of rs10483810 in RAD51 gene
      is associated with an increased risk of advanced AMD, especially bilateral AMD,
      in Chinese population.

PMID- 23868023
TI  - Marin-Amat syndrome: a case of acquired facial synkinesis.

PMID- 23868024
TI  - Brainstem tuberculosis.
AB  - We present a case of a 38-year-old-man who presented with 1-week history of
      developing weakness of peripheral and cranial nerves. His MRI scan of the brain
      showed a large cavitating lesion at the brainstem and two further lesions of the
      right cerebral cortex and his CT chest showed features of old tuberculosis (TB).
      The identification of acid-fast bacilli was confirmed by analysis of
      bronchoalveolar lavage taken during bronchoscopy. He was started on anti-TB
      medications and repeat MRI 3 months later confirmed shrinkage of the cavitating
      lesion. 

PMID- 23868025
TI  - Cardiac tamponade: an initial presentation of SLE.
AB  - A 45-year-old woman presented with dyspnoea, chest pain, orthopnoea and bilateral
      leg oedema. On admission, she was found to have nephrotic syndrome and global
      pericardial effusion with impending tamponade for which pericardiocentesis was
      performed. The diagnosis of systemic lupus erythematosus was made based on the
      clinical and biochemical findings. She was also started on dialysis and
      immunosuppressants for lupus nephritis. 

PMID- 23868026
TI  - The adult Tillaux fracture: one not to miss.
AB  - This case is a rare adult type Tillaux fracture. This fracture should be
      diagnosed in the emergency department. The fracture requires careful evaluation
      with awareness of associated injury. Standard radiological views (antero
      posterior and lateral) of the ankle may not clearly show the fracture
      displacement hence, an oblique view is required. The fracture should be managed
      by the emergency physician, if the displacement is less than 2 mm, by
      immobilising with a non-weight bearing cast or ankle braces for 6 weeks. If the
      fracture fragment is displaced more than 2 mm, it should be treated by closed
      reduction failing which open reduction and internal fixation is the standard
      practice. 

PMID- 23868027
TI  - An unusual cause of acute abdominal pain in a young man.

PMID- 23868028
TI  - Enhancement of photocatalytic H2 evolution on Zn(0.8)Cd(0.2)S loaded with CuS as
      cocatalyst and its photogenerated charge transfer properties.
AB  - CuS/Zn(0.8)Cd(0.2)S composites have been successfully prepared by simple
      hydrothermal and cation exchange method. The Cu species loaded on
      Zn(0.8)Cd(0.2)S, together with the intimate contact formed between CuS and
      Zn(0.8)Cd(0.2)S, was clearly demonstrated with X-ray photoelectron spectroscopy
      and transmission electron microscopy. The optimized CuS/Zn(0.8)Cd(0.2)S
      photocatalyst has a high H2 evolution rate of 2792 MUmol g(-1) h(-1) at CuS
      content of 3 wt% and the apparent quantum efficiency of 36.7% at 420 nm. The
      photophysical mechanism of the photocatalytic activity was investigated with the
      help of surface photovoltage spectroscopy (SPS) and transient photovoltage (TPV)
      techniques. The results revealed that photogenerated charge separation efficiency
      in Zn(0.8)Cd(0.2)S was enhanced and the photogenerated electrons were trapped by
      the loaded CuS, which benefits photo-reduction. Those were the reasons for
      significant enhancement in the photocatalytic H2 evolution from water splitting.

PMID- 23868029
TI  - Follicle measurements using sonography-based automated volume count accurately
      predict the yield of mature oocytes in in vitro fertilization/intracytoplasmic
      sperm injection cycles.
AB  - AIMS: We define criteria to predict the number of mature oocytes using automated
      three-dimensional (3D) ultrasound follicle measurements. METHODS: Fifty in vitro
      fertilization/intracytoplasmic sperm injection patients underwent automated 3D
      echographic monitoring by a single researcher following the stimulation
      procedure. Classic criteria for triggering oocyte maturation as defined in the
      literature were utilized. 3D parameters, including the follicular volume and
      follicle diameter calculated from the volume measurement, were related to the
      oocyte count, mature oocyte count and the number of observed fertilized oocytes.
      RESULTS: We found that when oocyte maturation was induced, 55% of the total
      follicles with a diameter of at least 10 mm had a volume of at least 1.5 cm3. The
      number of mature eggs that were retrieved was correlated with the number of
      follicles observed with a volume of at least 1 cm3 or a calculated follicle
      diameter of at least 12 mm. CONCLUSION: Sonography-based automated volume count
      measurements of follicle volume and reconstructed follicle diameter can be used
      to reliably predict the number of mature oocytes.

PMID- 23868030
TI  - Experimental investigation of the penetration of ultrasound nanobubbles in a
      gastric cancer xenograft.
AB  - Nanobubbles as a type of ultrasound contrast agent have attracted much interest
      in recent years due to their many advantages, such as strong penetrating power
      and high stability. However, there is still insufficient morphological evidence
      concerning gas-filled nanobubbles in tumor tissue spaces and tumor angiogenesis.
      We used a gastric cancer xenograft as an example to study this question.
      Nanobubbles with a particle size of 435.2 +/- 60.53 nm were prepared and compared
      with SonoVue(r) microbubbles in vitro and in vivo, and they exhibited a superior
      contrast imaging effect. After excluding the impact of the nanobubbles in blood
      vessels through saline flush, we used an ultrasound burst and frozen sectioning
      to investigate the distribution of nanobubbles in the gastric cancer xenografts
      and confirmed this by transmission electron microscopy. Preliminary results
      showed that the nanobubbles were able to pass through the gaps between the
      endothelial cells in the tumor vascular system to enter the tissue space. These
      findings could provide morphological evidence for extravascular ultrasound
      imaging of tumors and serve as a foundation for the application of nanobubbles in
      extravascular tumor-targeted ultrasonic diagnostics and therapy.

PMID- 23868031
TI  - Alternatives for the intensive follow-up after curative resection of colorectal
      cancer. Potential novel biomarkers for the recommendations.
AB  - Early diagnosis of recurrence and metastasis of colorectal cancer following
      surgery of curative intent is of vital importance in terms of survival and
      quality of life. The consistent implementation of appropriate patient follow-up
      strategy is therefore essential. Debates over the methodology, evaluation and
      strategy of follow-up have been known for many years, and continue today. By
      introducing several follow-up models, the present paper offers different options
      featuring certain individual, national and international, conceptual and
      financial aspects. Colorectal cancer is an important public health concern due to
      its destructive nature and frequency, it is therefore essential to develop new
      monitoring strategies, involving new biomarkers and extensive clinical
      validation. Since the recurrence rate is very high in high-risk patients, the
      improvement of individual patient risk estimates and the utilization of a
      corresponding follow-up model require broad international co-operation and common
      practice, along with the determination of optimal levels of evidence. 

PMID- 23868033
TI  - [The laparoscopic Vecchietti technique for vaginal agenesis].
AB  - AIM: To evaluate feasibility and surgical long term, anatomic and functional
      results of the laparoscopic Vecchietti procedure to treat women with vaginal
      agenesis. METHODS: We reported six cases of patients with a Mayer-Rokitansky
      Kuster-Hauser syndrome. The surgical procedure was the same for all patients. The
      results have been evaluated on the operative time, the intra and postoperative
      complications, the antalgic drugs consumption, the transit recovery, the hospital
      stay, the neovagina length, and the post operative sexual satisfaction. RESULTS:
      The mean operative time was 77.5 minutes. The mean paracetamol consumption was:
      9.8 g. The mean transit recovery, and hospital stay were: 2 days, 9.8 days,
      respectively. No intra or postoperative complication occurred. The mean neovagina
      length evaluated at one year follow-up visit was 7.5 cm. Five patients have
      regular sexual activity. Three of them reported sexual satisfaction and showed
      having orgasm (clitoral: 3 cases, clitoral and vaginal: 2 cases). The 2 remaining
      patients reported dyspareunia. The global satisfaction index was of 71.6%.
      CONCLUSION: This surgical technique appeared to be safe, effective and
      reproducible. It allowed to obtain a neovagina with enough length and have
      encouraging results on sexual functioning Laparoscopy reduces the psychological
      and aesthetic consequences of surgery, especially for these young patients
      already distressed by their malformation.

PMID- 23868032
TI  - Facilitated by nature and agriculture: performance of a specialist herbivore
      improves with host-plant life history evolution, domestication, and breeding.
AB  - Plant defenses against herbivores are predicted to change as plant lineages
      diversify, and with domestication and subsequent selection and breeding in the
      case of crop plants. We addressed whether defense against a specialist herbivore
      declined coincidently with life history evolution, domestication, and breeding
      within the grass genus Zea (Poaceae). For this, we assessed performance of corn
      leafhopper (Dalbulus maidis) following colonization of one of four Zea species
      containing three successive transitions: the evolutionary transition from
      perennial to annual life cycle, the agricultural transition from wild annual
      grass to primitive crop cultivar, and the agronomic transition from primitive to
      modern crop cultivar. Performance of corn leafhopper was measured through seven
      variables relevant to development speed, survivorship, fecundity, and body size.
      The plants included in our study were perennial teosinte (Zea diploperennis),
      Balsas teosinte (Zea mays parviglumis), a landrace maize (Zea mays mays), and a
      hybrid maize. Perennial teosinte is a perennial, iteroparous species, and is
      basal in Zea; Balsas teosinte is an annual species, and the progenitor of maize;
      the landrace maize is a primitive, genetically diverse cultivar, and is ancestral
      to the hybrid maize; and, the hybrid maize is a highly inbred, modern cultivar.
      Performance of corn leafhopper was poorest on perennial teosinte, intermediate on
      Balsas teosinte and landrace maize, and best on hybrid maize, consistent with our
      expectation of declining defense from perennial teosinte to hybrid maize.
      Overall, our results indicated that corn leafhopper performance increased most
      with the agronomic transition, followed by the life history transition, and least
      with the domestication transition.

PMID- 23868034
TI  - The Budd-Chiari syndrome.
AB  - BACKGROUND: The Budd-Chiari syndrome is a rare disease, often fatal if not
      treated optimally. It is characterized by a blocked hepatic venous outflow tract.
      aim: This review attempted to present pathophysiology, aetiologies,diagnosis and
      therapeutic modalities of the Budd-Chiari syndrome. METHODS: Review of
      literature. RESULTS: Budd-Chiari syndrome is a complex disease with a wide
      spectrum of aetiologies and presentations. Hematologic abnormalities,
      particularly myeloproliferative disorders, are the most common causes of the Budd
      Chiari syndrome. The clinical presentation is governed by the extent and rapidity
      of the hepatic vein occlusion. Doppler-ultrasound, computed tomography or
      magnetic resonance imaging of hepatic veins and inferior vena cava are usually
      successful in demonstrating non-invasively the obstacle or its consequences. A
      therapeutic strategy has been proposed where anticoagulation, correction of risk
      factors, diuretics and prophylaxis for portal hypertension are used first; then
      angioplasty for shortlength venous stenosis; then Transjugular Intrahepatic
      Portosystemic Shunt (TIPS); and ultimately liver transplantation. Treatment
      progression is dictated by the response to previous therapy. This strategy has
      achieved 5-year survival rates approaching 70%. Medium-term prognosis depends on
      the severity of liver disease. CONCLUSION: The diagnosis of the Budd-Chiari
      syndrome must be considered in any patients with acute or chronic liver disease.
      Management of this syndrome should follow a step by step strategy.

PMID- 23868035
TI  - [Study of a Tunisian population of children with learning disorders].
AB  - BACKGROUND: Learning disorders are increasingly a concern for Tunisians parents.
      These difficulties are divided into two groups: specific learning disabilities
      and non-specific learning disorders. AIM: Our work is part of a federated
      research project. Our aim is to determine the incidence, etiology and management
      of learning disorders in the region of Sfax. METHODS: We conducted a descriptive
      cross-sectional study on a population of 304 children assessed by their teachers
      as having academic difficulty. A multidisciplinary assessment including a
      neurological examination, an assessment of score of intelligence and language
      assessment has been performed for 209 children. RESULTS: Referring to our sample,
      learning disorders affect 21.3% of children in the region Sfax. The frequency of
      specific learning disorder is estimated at 10.3% (reading disorder 5.9%,
      dyscalculia 2.4%, reading disorder associated with dyscalculia 2%). Non-specific
      learning disorders were found in 11% of children. Etiologies in this group were
      dominated by mental retardation (2.1%), inappropriate education (2.3%).
      CONCLUSION: Our study revealed the high frequency of learning difficulties. It
      allows us to distinguish between specific learning disabilities and non specific
      learning disorders secondary to neurological or precarious socio-economic
      conditions. However, the profile and severity of specific learning disorders
      could not be studied due to the lack of standardized Arabic tests in Tunisia. In
      countries with a lack of professional and specialized unit care as in Tunisia,
      reading interventions in school should be proposed. Only children with remaining
      difficulties after this training will be sent to specialized professionals.

PMID- 23868036
TI  - The value of sonohysterography in the diagnosis of tubal patency among infertile
      patients.
AB  - BACKGROUND: Tubal pathology is one of the main causes of infertility. In the
      routine fertility work-up, our ability to evaluate tubal function is limited to
      tubal patency and peritubal adhesions. AIMS: To assess the value of
      sonohysteroography (SHG) in evaluation of tubal patency in infertile patients and
      to compare its results with hysterosalpingography and laparoscopy. methods: In
      this prospective study, 40 consecutive women were underwent three methods of
      exploration of tubal patency: hysterosalpingography, sonohysteroography and
      laparoscopy with dye test, within a period of 6 months. RESULTS: The Mean age of
      our patients was 32 +/- 5 years. Of the 40 women who were recruited, 30 had
      primary and 10 had secondary infertility. Altogether 80 tubes were exanimated by
      these 3 methods. Sonosalpingography showed patency in 51(63.7%) tubes,
      hysterosalpingography in 47 (58.7%) tubes, and laparoscopy in 52 (65%) tubes.
      Sonosalpingography and laparoscopy agreed in 70 out of 80 tubes (concordance,
      87.5%). As regards the appearance of the right and left tubes, the results of
      sonohysterography agreed with laparoscopy in 75% and 87.5%, respectively, while
      HSG agreed with laparoscopy in 64% and 54% respectively. CONCLUSION: SHG is
      useful in the assessment of tubal patency and its implication in the fertility
      workup as a simple and fast procedure can minimize costes and abus of
      sophisticated techniques.

PMID- 23868037
TI  - Prevalence and risk factor of renal dysfunction induced by bacterial infection
      other than spontaneous bacterial peritonitis in patients with cirrhosis.
AB  - BACKGROUND: Deterioration of renal function in cirrhotic patients with
      spontaneous bacterial peritonitis (SBP) is a predictor for inhospital mortality.
      However, the clinical significance of renal dysfunction during bacterial
      infection other than SBP is unknown. AIM: To investigate the prevalence and
      clinical significance of renal dysfunction due to bacterial infections other than
      SBP in patients with liver cirrhosis. METHODS: Retrospective data from in
      patients with bacterial infections other than SBP were analyzed. RESULTS: Eighty
      two patients were recruited for the analysis. Infection was located in urinary
      tract (41.5%), pneumonia (34.1%), biliary tract (3.7%), cellulitis (6.1%),
      gastrointestinal tract (4.9%) and bacteremia of unknown origin (9.7%). Renal
      dysfunction developed in 40 patients (48.8%), of which 13 patients had
      irreversible renal dysfunction. In the univariate and multivariate analysis, the
      initial MELD score, neutrophil count, bilirubin, and blood pressure were
      significant risk factors for renal dysfunction. CONCLUSION: The prevalence of
      renal dysfunction during bacterial infection other than SBP in patients with
      liver cirrhosis was 48.8%, and its development was related to the severity of the
      liver disease. Occurrence of irreversible renal dysfunction seemed to affect the
      prognosis of these patients.

PMID- 23868038
TI  - [Results of cardiac pacing: report of 188 patients].
AB  - BACKGROUND: Indications for permanent pacing are currently well codified. This
      treatment may, however, present complications AIM: To report the results of
      cardiac pacing and to identify predictive factors of pacing's complication.
      METHODS: We conducted a retrospective study of 188 consecutive patients admitted
      to the cardiology department of Mongi Slim university hospital in La Marsa
      between January 2005 and June 2011 and implanted with a single or dual chamber
      pacemaker. RESULTS: In our study, we had 92 men and 96 women (sexratio= 0.95).
      The mean age was 70.21 +/- 13 years. The indication for cardiac pacing was a high
      degree heart block in 74.46% of cases and a sick sinus syndrome in 15.95% of
      cases. The degeneration conduction tissue was the main etiology (72.34% of
      patients). Success implantation was obtained in 98.4%of cases. The main operative
      complication was the pneumothorax in 3 patients (1.59% of cases). At Long term,
      cumulative survival rate was 78.95%. Only operating time affects significantly
      the rate of early complications (p<0.001). Late complications were related to the
      valvular heart disease (p = 0.007), the ischemic etiology (p = 0.05), the oral
      antivitamine K treatment (p = 0.04) and the occurrence of early complication (p =
      0.002). CONCLUSION: Our hospital, which is considered as a small Center of
      cardiac pacing (less than 80 procedures/year) had a low complication rate as well
      as big centers.

PMID- 23868039
TI  - Serum copper, zinc and selenium levels in Tunisian patients with Parkinson's
      disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder.
      The etiology of this disease is still not fully clear, but free radicals have
      been proposed to cause neuronal injury. Metals play a key role in the
      intracellular oxidative balance. However their implication in the degeneration
      process remains unknown. AIM: To assess Cu, Zn and Se concentrations in serum of
      a group of PD patients in order to determinate, in comparison with age-matched
      controls, whether alteration in their levels could be involved in PD. METHODS: A
      serum level of 3 trace elements (Cu, Zn and Se) was investigated in 48 patients
      with PD and 36 matched controls using plasma atomic absorption spectrometry. We
      compared these parameters in PD patients with controls, and we also compared the
      variations within the PD group according to age, illness duration, stage of the
      disease and levodopa intake. RESULTS: Patients with PD had significantly lower Cu
      levels compared to controls. The mean Zn and Se levels in PD patients did not
      differ significantly from those of controls. Levodopa therapy, age, stage, and
      illness duration did not significantly influence the measured parameters.
      CONCLUSION: These results suggest that a disturbance of the plasmatic rate of Cu
      could be a marker of PD or at least, a risk factor for the development of this
      disease. Although zinc participates to the reduction of oxidative stress and the
      antioxidant role of the selenium, their implication in the onset of PD is not
      clearly established. Perspectives for the future could include antioxidant
      therapy. For this reason, other prospective studies should be conducted on this
      subject to elucidate the implication of trace elements in PD.

PMID- 23868040
TI  - [Dietary risk factors of undifferenced nasopharyngeal carcinoma : a case-control
      study].
AB  - BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is relatively high in
      Maghreb countries. This cancer is a model of multifactorial oncogenesis, but the
      role of food as risk factor in ethiopathogenesis of this tumor is not negligible.
      AIM: To identify the association between risk of NPC and some dietary factors in
      Morocco. METHODS: It is a case-control study including all new cases of NPC in
      our department between December 2009 and May 2010. Frequency consummation of
      foods was compared between cases and controls matched for age, sex and socio
      economic level. A high frequency consummation of a food was defined as
      consumption once or more by a week. Some traditional foods in Moroccan cooking
      like Harissa (hot red pepper), Qadid (mutton dried and salted), Khlii (dried
      meat, salted, spiced cooked and preserved in a mixture of oil and rendered beef
      fat) and Smen (rancid butter) were analyzed in this study. A conditional logistic
      regression was used to identify the association between dietary factors and the
      risk of NPC. RESULTS: Cases were more likely to have high frequency consumption
      of Harissa, Smen and Black Pepper, and less frequency consumption of fruts and
      vegetables. There was significant association between the risk of NPC and the
      frequency consumption of Qadid, khlii and cooking with olive oil. CONCLUSIONS:
      Some of these risk factors (Harissa, Black pepper) were found in 3 North Africain
      studies. This study indicates the involvement of dietary factors, and thus the
      lifestyle in the development of NPC and the need of biochemical analysis of food
      specimens to search for the carcinogenic agents.

PMID- 23868041
TI  - [Survey of general practioners in the management of diabetes in primary health
      facilities of Casablanca city, Morocco: opportunities and constraints].
AB  - BACKGROUND: Diabetes is a global health problem in full expansion, because of its
      increasing frequency, it frightening complications and the costs of its medical
      covering. AIM: In this study, we tried to make the current situation of the
      diabetes management in first-line public structures of the city of Casablanca.
      METHODS: The survey of transverse observation to descriptive aiming was conducted
      using a pre questionnaire tested and selfadministered. RESULTS: It shows that
      46.7 % of the questioned general practitioner judged that the quantity and the
      quality of average therapeutic existing in the center were insufficient to meet
      the needs for their diabetic patients. The weak socio-economic statute of the
      patients (78.8% of the cases), the lack of personnel (76.6%), the low educational
      level of patients (75.2%) and the problem of access to hospital (73.3%)
      constituted major problems of the correct diabetic medical covering. However, the
      majority of the doctors (98.1%) estimated to need training on diabetes
      management. The most required topics requested are: The control of the insulin
      treatment (97%), the diabetic education (91%) and the follow-up of diabetic
      (89%). CONCLUSION: The training of general practitioners particularly motivated
      and interested in diabetes could be the solution to improve the management of
      diabetes especially because of the lack of specialists in our country.

PMID- 23868042
TI  - Giant condyloma in pregnancy.

PMID- 23868043
TI  - [Rudimentary uterine horn pregnancy].

PMID- 23868044
TI  - [Successful treatment of a wide iatrogenic esophageal perforation after late
      implentation of double covered metal prothesis].

PMID- 23868045
TI  - [Acute kidney failure in association with Mediterranean spotted fever].

PMID- 23868046
TI  - [Sarcoidosis revealed by bilateral dacryoadenitis].

PMID- 23868047
TI  - [Primary Sjogren's syndrome and collagenous colitis].

PMID- 23868048
TI  - [Poems syndrome].

PMID- 23868049
TI  - [Endovascular treatment of an aneurysm of the abdominal aorta secondary to
      Behcet's disease].

PMID- 23868050
TI  - Cutaneous metastatic Crohn's disease of the abdominal wall: an exceptional
      location.

PMID- 23868051
TI  - Blunt trauma causing horseshoe kidney rupture: conservative management.

PMID- 23868052
TI  - [Retroperitoneal gangrene in perforated appendicitis].

PMID- 23868053
TI  - Periocular necrotizing fasciitis causing blindness.
AB  - IMPORTANCE: Periocular necrotizing fasciitis is a rare but potentially
      devastating disease, accompanied by high rates of morbidity and mortality.
      OBSERVATIONS: We report 5 cases of periocular necrotizing fasciitis resulting in
      severe vision loss, 3 of which required exenteration to contain the disease and
      only 1 of which recovered vision. Three cases were caused by group A
      streptococcus; 1, by methicillin-resistant Staphylococcus aureus; and 1, by
      Streptococcus anginosus constellatus. CONCLUSIONS AND RELEVANCE: Providers should
      maintain a high clinical suspicion for necrotizing fasciitis and distinguish it
      from more common forms of cellulitis. As seen in these 5 cases, periocular
      necrotizing fasciitis may cause severe visual loss more often than previously
      recognized. To our knowledge, this is also the first report of Streptococcus
      anginosus constellatus causing necrotizing fasciitis.

PMID- 23868054
TI  - Carbon-core silver-shell nanodots as sensitizers for phototherapy and
      radiotherapy.
AB  - Spherical carbon nanoparticles (carbon nanodots) with a silver shell were
      investigated as potential sensitizing agents. The cytotoxicity of the combination
      of ultraviolet radiation or x-rays with the nanodots was examined in cancer cells
      in vitro. The cell viability decreased following the exposure to the radiation.
      The carbon nanodots enhanced the radiation effects by significantly reducing the
      amount of surviving cells compared to that of the cells exposed only to the
      radiation. Carbon-core silver-shell nanodots can be proposed as a bimodal
      sensitization platform for biological and medicinal applications employing non
      ionizing or ionizing radiation.

PMID- 23868055
TI  - A prospective proteomic-based study for identifying potential biomarkers for the
      diagnosis of cholangiocarcinoma.
AB  - BACKGROUND: Cholangiocarcinoma (CCA) is becoming a common fatal hepatic tumor.
      Early detection of CCA is hampered by the absence of a sufficiently accurate and
      noninvasive diagnostic test. Proteomic analysis would be a powerful tool to
      identify potential biomarkers of this cancer. AIMS: This study aims to identify
      new protein markers that are specific for CCA using proteomic approaches and to
      evaluate the performance of S100 calcium-binding protein A9 (S100A9) and
      chaperonin-containing TCR1, subunit 3 (CCTgamma) as diagnostic markers for
      screening test of CCA. METHODS: Two-dimensional differential gel electrophoresis
      (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) mass spectrometry were used to analyze and screen biomarker
      candidates in the proteomes of five human CCA samples and five healthy control
      samples. Subsequently, two potential biomarkers, S100A9 and CCTgamma, were chosen
      for validation and analysis by immunohistochemical methods using CCA tissue
      microarrays. RESULTS: Twenty protein spots were significantly elevated and five
      protein spots were downregulated in all patients (p < 0.05). The positive rate
      was significantly higher in patients with CCA (48 +/- 35%) compared with the
      normal liver control group (5 +/- 10%, p < 0.001), the hepatocellular carcinoma
      group (15 +/- 20%, p < 0.001), and the cirrhosis group (12 +/- 16%, p < 0.001). A
      greater proportion of patients with CCA were positive for CCTgamma (72 +/- 18%)
      compared with the normal liver control group (43 +/- 22%, p < 0.001), the
      hepatocellular carcinoma group (45 +/- 20%, p < 0.001), and the cirrhosis group
      (39 +/- 25%, p < 0.001). CONCLUSIONS: Combined comparative proteomic analysis
      using 2-D DIGE and MALDI-TOF is an effective method for identifying
      differentially expressed proteins in CCA tissues. The expression of S100A9 and
      CCTgamma showed promise as novel diagnostic markers for CCA.

PMID- 23868056
TI  - Multilayer myofascial-mesh repair for giant midline incisional hernias: a novel
      advantageous combination of old and new techniques.
AB  - BACKGROUND: The components separation technique has been proposed as the best
      solution when facing large abdominal wall defects. In counterpart, this sometimes
      comes at the price of high rates of wound complications and recurrence. Moreover,
      the components separation method alone seems insufficient for huge defects, in
      which it is impossible to reapproximate the rectus muscles without tension. For
      these cases, we illustrate a novel operation using a modified components
      separation technique. METHODS: Twenty-eight patients with giant midline
      incisional hernias were treated with a combination of the components separation
      (bilateral sliding rectus abdominis advancement flaps), an autologous multilayer
      repair, and a retromuscular mesh reinforcement. RESULTS: Twenty-four (85%)
      patients have been analyzed. Transverse defect size ranged from 15 to 25 cm
      (average, 18.8 cm). Wound complications occurred in nine (37%) cases; three of
      them required drainage of a subcutaneous abscess. After a mean follow-up of 22
      (range, 12-48) months, one (4%) recurrence was identified. CONCLUSIONS:
      Multilayer myofascial-mesh repair was associated with a low recurrence rate, and
      wound complications were managed without issues. This approach is a reliable
      technique for most surgeons and may constitute a new part of the armamentarium
      for the repair of challenging defects.

PMID- 23868057
TI  - Five-year cohort study of open pancreatic necrosectomy for necotizing
      pancreatitis suggests it is a safe and effective operation.
AB  - INTRODUCTION: Despite advances in the management of necrotizing pancreatitis,
      open necrosectomy remains an important management option for necrotizing
      pancreatitis, and patients undergoing necrosectomy suffer significant morbidity
      and mortality. The aim of this study was to report the outcomes of open
      necrosectomy from a recent large cohort of patients with necrotizing
      pancreatitis. METHODS: Data are reported from a cohort of 276 consecutive
      patients with necrotizing pancreatitis who underwent open surgical debridement.
      Nutritional status, nutritional methods, bleeding, infection, demarcation of
      necrotic tissues, and time from onset of disease were scored. Scores >= 10 were
      considered as an indication for debridement. RESULTS: One hundred sixty-two
      (58.7%) and 52 (18.8%) patients underwent minimally invasive peritoneal and
      retroperitoneal drainage, respectively, before necrosectomy. Median delay from
      disease onset to debridement was 48 days. Fifty-five patients (19.9%) underwent
      more than one operation; 352 operations were performed in total. There were 17
      deaths (6.2%) postoperatively. CONCLUSION: This study demonstrated the results
      for open debridement in a recent large cohort of patients. Although minimally
      invasive necrosectomy has been developed in recent years, open necrosectomy
      remains an important approach for the debridement of necrotizing pancreatitis
      effectively and safely.

PMID- 23868058
TI  - E2F1 in renal cancer: Mr Hyde disguised as Dr Jekyll?
AB  - The transcription factor E2F1 has both oncogenic and tumour suppressor
      properties, depending on the context. Clarifying the function of E2F1 in
      different types of cancer is relevant because in those situations in which it
      acts as an oncogene there may be a route for therapeutic interference. Renal cell
      carcinoma is the most frequent form of kidney cancer in adults and inactivation
      of the von Hippel-Lindau (VHL) gene underlies most cases. This malignancy
      represents a challenge for standard therapies due to drug- and radio-resistance,
      effects that fit well within the scope of functions of E2F1. A new report by Mans
      et al postulates that up-regulation of E2F1 in VHL-defective renal cell carcinoma
      induces cell senescence and can thus be considered a good prognostic factor. Here
      we discuss these findings in a wider context and propose that E2F1 may actually
      not play a uniform role in renal cell carcinoma but rather an ambiguous one whose
      deeper understanding could have practical implications.

PMID- 23868059
TI  - H-Ras transfers from B to T cells via tunneling nanotubes.
AB  - Lymphocytes form cell-cell connections by various mechanisms, including
      intercellular networks through actin-supported long-range plasma membrane (PM)
      extensions, termed tunneling nanotubes (TNTs). In this study, we tested in vitro
      whether TNTs form between human antigen-presenting B cells and T cells following
      cell contact and whether they enable the transfer of PM-associated proteins, such
      as green fluorescent protein (GFP)-tagged H-Ras (GFP-H-Ras). To address this
      question, we employed advanced techniques, including cell trapping by optical
      tweezers and live-cell imaging by 4D spinning-disk confocal microscopy. First, we
      showed that TNTs can form after optically trapped conjugated B and T cells are
      being pulled apart. Next, we determined by measuring fluorescence recovery after
      photobleaching that GFP-H-Ras diffuses freely in the membrane of TNTs that form
      spontaneously between B and T cells during coculturing. Importantly, by 4D time
      lapse imaging, we showed that GFP-H-Ras-enriched PM patches accumulate at the
      junction between TNTs and the T-cell body and subsequently transfer to the T-cell
      surface. Furthermore, the PM patches adopted by T cells were enriched for another
      B-cell-derived transmembrane receptor, CD86. As predicted, the capacity of GFP-H
      Ras to transfer between B and T cells, during coculturing, was dependent on its
      normal post-transcriptional lipidation and consequent PM anchorage. In summary,
      our data indicate that TNTs connecting B and T cells provide a hitherto
      undescribed route for the transfer of PM patches containing, for example, H-Ras
      from B to T cells. 

PMID- 23868060
TI  - Mitochondrial DNA damage induces apoptosis in senescent cells.
AB  - Senescence is a cellular response to damage and stress. The senescence response
      prevents cancer by suppressing the proliferation of cells with a compromised
      genome and contributes to optimal wound healing in normal tissues. Persistent
      senescent cells are also thought to drive aging and age-associated pathologies
      through their secretion of inflammatory factors that modify the tissue
      microenvironment and alter the function of nearby normal or transformed cells.
      Understanding how senescent cells alter the microenvironment would be aided by
      the ability to induce or eliminate senescent cells at will in vivo. Here, we
      combine the use of the synthetic nucleoside analog ganciclovir (GCV) with herpes
      simplex virus thymidine kinase (HSVtk) activity to create or eliminate senescent
      human cells. We show that low concentrations of GCV induce senescence through the
      accumulation of nuclear DNA damage while higher concentrations of GCV, similar to
      those used in vivo, kill non-dividing senescent cells via mitochondrial DNA
      (mtDNA) damage and caspase-dependent apoptosis. Using this system, we effectively
      eliminated xenografted normal human senescent fibroblasts or induced senescence
      in human breast cancer cells in vivo. Thus, cellular senescence and mtDNA damage
      are outcomes of synthetic nucleoside analog treatment, indicating that the GCV
      HSVtk combination can be used effectively to promote the targeted formation or
      eradication of senescent cells. 

PMID- 23868062
TI  - Pax8 has a critical role in epithelial cell survival and proliferation.
AB  - The transcription factor Pax8, a member of the Paired-box gene family, is a
      critical regulator required for proper development and differentiation of thyroid
      follicular cells. Despite being Pax8 well characterized with respect to its role
      in regulating genes responsible for thyroid differentiation, its involvement in
      cell survival and proliferation has been hypothesized but remains unclear. Here,
      we show that Pax8 overexpression significantly increases proliferation and colony
      forming efficiency of Fischer rat thyroid line 5 epithelial cells, although it is
      not sufficient to overcome their hormone dependence. More interestingly, we show
      that Pax8-specific silencing induces apoptosis through a p53-dependent pathway
      that involves caspase-3 activation and cleavage of poly(ADP)ribose polymerase.
      Our data indicate that tumor protein 53 induced nuclear protein 1 (tp53inp1), a
      positive regulator of p53-dependent cell cycle arrest and apoptosis, is a
      transcriptional target of Pax8 and is upregulated by Pax8 knockdown. Remarkably,
      tp53inp1 silencing significantly abolishes Pax8-induced apoptosis thus suggesting
      that tp53inp1 may be the mediator of the observed effects. In conclusion, our
      data highlight that Pax8 is required for the survival of differentiated
      epithelial cells and its expression levels are able to modulate the proliferation
      rate of such cells. 

PMID- 23868061
TI  - Reolysin is a novel reovirus-based agent that induces endoplasmic reticular
      stress-mediated apoptosis in pancreatic cancer.
AB  - Activating mutation of KRas is a genetic alteration that occurs in the majority
      of pancreatic tumors and is therefore an ideal therapeutic target. The ability of
      reoviruses to preferentially replicate and induce cell death in transformed cells
      that express activated Ras prompted the development of a reovirus-based
      formulation for cancer therapy called Reolysin. We hypothesized that Reolysin
      exposure would trigger heavy production of viral products leading to endoplasmic
      reticular (ER) stress-mediated apoptosis. Here, we report that Reolysin treatment
      stimulated selective reovirus replication and decreased cell viability in KRas
      transformed immortalized human pancreatic duct epithelial cells and pancreatic
      cancer cell lines. These effects were associated with increased expression of ER
      stress-related genes, ER swelling, cleavage of caspase-4, and splicing of XBP-1.
      Treatment with ER stress stimuli including tunicamycin, brefeldin A, and
      bortezomib (BZ) augmented the anticancer activity of Reolysin. Cotreatment with
      BZ and Reolysin induced the simultaneous accumulation of ubiquitinated and viral
      proteins, resulting in enhanced levels of ER stress and apoptosis in both in
      vitro and in vivo models of pancreatic cancer. Our collective results demonstrate
      that the abnormal protein accumulation induced by the combination of Reolysin and
      BZ promotes heightened ER stress and apoptosis in pancreatic cancer cells and
      provides the rationale for a phase I clinical trial further investigating the
      safety and efficacy of this novel strategy. 

PMID- 23868063
TI  - HSP70 inhibition by 2-phenylethynesulfonamide induces lysosomal cathepsin D
      release and immunogenic cell death in primary effusion lymphoma.
AB  - Heat-shock protein (HSP) 70 is aberrantly expressed in different malignancies and
      has a cancer-specific cell-protective effect. As such, it has emerged as a
      promising target for anticancer therapy. In this study, the effect of the HSP70
      specific inhibitor (PES), also Pifitrin-MU, on primary effusion lymphoma (PEL)
      cell viability was analyzed. PES treatment induced a dose- and time-dependent
      cytotoxic effect in BC3 and BCBL1 PEL cells by inducing lysosome membrane
      permeabilization, relocation of cathepsin D in the cytosol, Bid cleavage,
      mitochondrial depolarization with release and nuclear translocation of apoptosis
      activating factor. The PES-induced cell death in PEL cells was characterized by
      the appearance of Annexin-V/propidium iodide double-positive cells from the early
      times of treatment, indicating the occurrence of an additional type of cell death
      other than apoptosis, which, accordingly, was not efficiently prevented by the
      pan-caspase inhibitor Z-VAD-fmk. Conversely, PES-induced cell death was robustly
      reduced by pepstatin A, which inhibits Bid and caspase 8 processing. In addition,
      PES was responsible for a block of the autophagic process in PEL cells. Finally,
      we found that PES-induced cell death has immunogenic potential being able to
      induce dendritic cell activation. 

PMID- 23868064
TI  - Interaction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and
      protects from apoptotic cell death under oxidative stress.
AB  - Sirtuin 3 (Sirt3), a major mitochondrial NAD(+)-dependent deacetylase, targets
      various mitochondrial proteins for lysine deacetylation and regulates important
      cellular functions such as energy metabolism, aging, and stress response. In this
      study, we identified the human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA
      repair enzyme that excises 7,8-dihydro-8-oxoguanine (8-oxoG) from damaged genome,
      as a new target protein for Sirt3. We found that Sirt3 physically associated with
      OGG1 and deacetylated this DNA glycosylase and that deacetylation by Sirt3
      prevented the degradation of the OGG1 protein and controlled its incision
      activity. We further showed that regulation of the acetylation and turnover of
      OGG1 by Sirt3 played a critical role in repairing mitochondrial DNA (mtDNA)
      damage, protecting mitochondrial integrity, and preventing apoptotic cell death
      under oxidative stress. We observed that following ionizing radiation, human
      tumor cells with silencing of Sirt3 expression exhibited deteriorated oxidative
      damage of mtDNA, as measured by the accumulation of 8-oxoG and 4977 common
      deletion, and showed more severe mitochondrial dysfunction and underwent greater
      apoptosis in comparison with the cells without silencing of Sirt3 expression. The
      results reported here not only reveal a new function and mechanism for Sirt3 in
      defending the mitochondrial genome against oxidative damage and protecting from
      the genotoxic stress-induced apoptotic cell death but also provide evidence
      supporting a new mtDNA repair pathway. 

PMID- 23868065
TI  - Glucose starvation induces cell death in K-ras-transformed cells by interfering
      with the hexosamine biosynthesis pathway and activating the unfolded protein
      response.
AB  - Cancer cells, which use more glucose than normal cells and accumulate
      extracellular lactate even under normoxic conditions (Warburg effect), have been
      reported to undergo cell death under glucose deprivation, whereas normal cells
      remain viable. As it may be relevant to exploit the molecular mechanisms
      underlying this biological response to achieve new cancer therapies, in this
      paper we sought to identify them by using transcriptome and proteome analysis
      applied to an established glucose-addicted cellular model of transformation,
      namely, murine NIH-3T3 fibroblasts harboring an oncogenic K-RAS gene, compared
      with parental cells. Noteworthy is that the analyses performed in high- and low
      glucose cultures indicate that reduction of glucose availability induces,
      especially in transformed cells, a significant increase in the expression of
      several unfolded protein response (UPR) hallmark genes. We show that this
      response is strictly associated with transformed cell death, given that its
      attenuation, by reducing protein translation or by increasing cell protein
      folding capacity, preserves the survival of transformed cells. Such an effect is
      also observed by inhibiting c-Jun NH2-terminal kinase, a pro-apoptotic signaling
      mediator set downstream of UPR. Strikingly, addition of N-acetyl-D-glucosamine, a
      specific substrate for the hexosamine biosynthesis pathway (HBP), to glucose
      depleted cells completely prevents transformed cell death, stressing the
      important role of glucose in HBP fuelling to ensure UPR attenuation and increased
      cell survival. Interestingly, these results have been fully recognized in a human
      model of breast cancer, MDA-MB-231 cells. In conclusion, we show that glucose
      deprivation, leading to harmful accumulation of unfolded proteins in consequence
      of a reduction of protein glycosylation, induces a UPR-dependent cell death
      mechanism. These findings may open the way for new therapeutic strategies to
      specifically kill glycolytic cancer cells. 

PMID- 23868068
TI  - HDAC inhibition suppresses cardiac hypertrophy and fibrosis in DOCA-salt
      hypertensive rats via regulation of HDAC6/HDAC8 enzyme activity.
AB  - Background : Inhibition of histone deacetylase (HDAC) was reported to suppress
      cardiac hypertrophy and fibrosis in various hypertrophic animal models. However,
      the HDAC expression profile and HDAC enzyme activity have not yet been
      investigated in DOCA-salt hypertensive rats. Methods : Unilaterally
      nephrectomized rats were implanted with DOCA strips. DOCA-salt rats then received
      a control diet with vehicle or valproate. We measured the expression of cardiac
      hypertrophic markers, class I HDACs, class II HDACs, fibrosis, and HDAC enzyme
      activity. Results : Here we report that sodium valproate inhibits the cardiac
      hypertrophy accompanied by fibrosis in the heart of chronic hypertensive rats. We
      show that expression of GATA6 and HDAC6 is upregulated in DOCA-salt hypertension.
      In addition, HDAC6 and HDAC8 enzyme activity is attenuated by sodium valproate.
      Conclusion : These results suggest that a novel HDAC6- and HDAC8-selective
      inhibitor is needed to treat or prevent pathological cardiac hypertrophy. (c)
      2013 S. Karger AG, Basel. 

PMID- 23868069
TI  - Charge compensation assisted enhanced photoluminescence derived from Li-codoped
      MgAl2O4:Eu3+ nanophosphors for solid state lighting applications.
AB  - Highly-luminescent nanophosphors have a decisive role in solid-state lighting
      (SSL) as well as in field emission display (FED) applications due to their
      potential use in fabrication of nanophosphor based FED and solid state display
      devices. Herein, the red emitting highly-luminescent Eu(3+)-Li(+) co-doped
      magnesium aluminate (MgAl2O4) nanophosphors were synthesized by a customized sol
      gel route with an average particle size of 18 nm, which can be easily scaled up
      in a large quantity. The resulting nanophosphor exhibits hypersensitive red
      emission, peaking at 615 nm upon 394 nm excitation. Furthermore, comparative
      photoluminescence (PL) studies have been carried out for Eu(3+) doped and Eu(3+)
      doped-Li(+) co-doped magnesium aluminate (Li(+) co-doped MgAl2O4:Eu(3+))
      nanophosphors, which indicated that Li(+) co-doping significantly improves
      luminescence intensity along with good crystallinity. Moreover, the charge
      compensation by addition of Li(+) co-activator in MgAl2O4:Eu(3+) lattice led to
      the two fold enhancement of PL intensity. The obtained results suggest that this
      nanophosphor could be an ultimate choice for next generation advanced luminescent
      nanomaterials for solid state lighting and portable FED devices. 

PMID- 23868066
TI  - SAHA overcomes FLIP-mediated inhibition of SMAC mimetic-induced apoptosis in
      mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a highly pro-inflammatory malignancy that
      is rapidly fatal and increasing in incidence. Cytokine signaling within the pro
      inflammatory tumor microenvironment makes a critical contribution to the
      development of MPM and its resistance to conventional chemotherapy approaches.
      SMAC mimetic compounds (SMCs) are a promising class of anticancer drug that are
      dependent on tumor necrosis factor alpha (TNFalpha) signaling for their activity.
      As circulating TNFalpha expression is significantly elevated in MPM patients, we
      examined the sensitivity of MPM cell line models to SMCs. Surprisingly, all MPM
      cell lines assessed were highly resistant to SMCs either alone or when incubated
      in the presence of clinically relevant levels of TNFalpha. Further analyses
      revealed that MPM cells were sensitized to SMC-induced apoptosis by siRNA
      mediated downregulation of the caspase 8 inhibitor FLIP, an antiapoptotic protein
      overexpressed in several cancer types including MPM. We have previously reported
      that FLIP expression is potently downregulated in MPM cells in response to the
      histone deacetylase inhibitor (HDACi) Vorinostat (SAHA). In this study, we
      demonstrate that SAHA sensitizes MPM cells to SMCs in a manner dependent on its
      ability to downregulate FLIP. Although treatment with SMC in the presence of
      TNFalpha promoted interaction between caspase 8 and the necrosis-promoting RIPK1,
      the cell death induced by combined treatment with SAHA and SMC was apoptotic and
      mediated by caspase 8. These results indicate that FLIP is a major inhibitor of
      SMC-mediated apoptosis in MPM, but that this inhibition can be overcome by the
      HDACi SAHA. 

PMID- 23868067
TI  - Misguidance and modulation of axonal regeneration by Stat3 and Rho/ROCK signaling
      in the transparent optic nerve.
AB  - The use of the visual system played a major role in the elucidation of molecular
      mechanisms controlling axonal regeneration in the injured CNS after trauma. In
      this model, CNTF was shown to be the most potent known neurotrophic factor for
      axonal regeneration in the injured optic nerve. To clarify the role of the
      downstream growth regulator Stat3, we analyzed axonal regeneration and neuronal
      survival after an optic nerve crush in adult mice. The infection of retinal
      ganglion cells with adeno-associated virus serotype 2 (AAV2) containing wild-type
      (Stat3-wt) or constitutively active (Stat3-ca) Stat3 cDNA promoted axonal
      regeneration in the injured optic nerve. Axonal growth was analyzed in whole
      mounted optic nerves in three dimensions (3D) after tissue clearing.
      Surprisingly, with AAV2.Stat3-ca stimulation, axons elongating beyond the lesion
      site displayed very irregular courses, including frequent U-turns, suggesting
      massive directionality and guidance problems. The pharmacological blockade of
      ROCK, a key signaling component for myelin-associated growth inhibitors, reduced
      axonal U-turns and potentiated AAV2.Stat3-ca-induced regeneration. Similar
      results were obtained after the sustained delivery of CNTF in the axotomized
      retina. These results show the important role of Stat3 in the activation of the
      neuronal growth program for regeneration, and they reveal that axonal misguidance
      is a key limiting factor that can affect long-distance regeneration and target
      interaction after trauma in the CNS. The correction of axonal misguidance was
      associated with improved long-distance axon regeneration in the injured adult
      CNS. 

PMID- 23868070
TI  - Taking the perfect nuclear image: quality control, acquisition, and processing
      techniques for cardiac SPECT, PET, and hybrid imaging.
AB  - Nuclear Cardiology for the past 40 years has distinguished itself in its ability
      to non-invasively assess regional myocardial blood flow and identify obstructive
      coronary disease. This has led to advances in managing the diagnosis, risk
      stratification, and prognostic assessment of cardiac patients. These advances
      have all been predicated on the collection of high quality nuclear image data.
      National and international professional societies have established guidelines for
      nuclear laboratories to maintain high quality nuclear cardiology services. In
      addition, laboratory accreditation has further advanced the goal of the
      establishing high quality standards for the provision of nuclear cardiology
      services. This article summarizes the principles of nuclear cardiology single
      photon emission computed tomography (SPECT) and positron emission tomography
      (PET) imaging and techniques for maintaining quality: from the calibration of
      imaging equipment to post processing techniques. It also will explore the quality
      considerations of newer technologies such as cadmium zinc telleride (CZT)-based
      SPECT systems and absolute blood flow measurement techniques using PET. 

PMID- 23868071
TI  - Quantitative myocardial perfusion imaging by cardiovascular magnetic resonance
      and positron emission tomography.
AB  - Recent studies have demonstrated that a detailed knowledge of the extent of
      angiographic coronary artery disease (CAD) is not a prerequisite for clinical
      decision making, and the clinical management of patients with CAD is more and
      more focused towards the identification of myocardial ischemia and the
      quantification of ischemic burden. In this view, non-invasive assessment of
      ischemia and in particular stress imaging techniques are emerging as preferred
      and non-invasive options. A quantitative assessment of regional myocardial
      perfusion can provide an objective estimate of the severity of myocardial injury
      and may help clinicians to discriminate regions of the heart that are at
      increased risk for myocardial infarction. Positron emission tomography (PET) has
      established itself as the reference standard for myocardial blood flow (MBF) and
      myocardial perfusion reserve (MPR) quantification. Cardiac magnetic resonance
      (CMR) is increasingly used to measure MBF and MPR by means of first-pass signals,
      with a well-defined diagnostic performance and prognostic value. The aim of this
      article is to review the currently available evidence on the use of both PET and
      CMR for quantification of MPR, with particular attention to the studies that
      directly compared these two diagnostic methods. 

PMID- 23868073
TI  - Large-scale gene function analysis with the PANTHER classification system.
AB  - The PANTHER (protein annotation through evolutionary relationship) classification
      system (http://www.pantherdb.org/) is a comprehensive system that combines gene
      function, ontology, pathways and statistical analysis tools that enable
      biologists to analyze large-scale, genome-wide data from sequencing, proteomics
      or gene expression experiments. The system is built with 82 complete genomes
      organized into gene families and subfamilies, and their evolutionary
      relationships are captured in phylogenetic trees, multiple sequence alignments
      and statistical models (hidden Markov models or HMMs). Genes are classified
      according to their function in several different ways: families and subfamilies
      are annotated with ontology terms (Gene Ontology (GO) and PANTHER protein class),
      and sequences are assigned to PANTHER pathways. The PANTHER website includes a
      suite of tools that enable users to browse and query gene functions, and to
      analyze large-scale experimental data with a number of statistical tests. It is
      widely used by bench scientists, bioinformaticians, computer scientists and
      systems biologists. In the 2013 release of PANTHER (v.8.0), in addition to an
      update of the data content, we redesigned the website interface to improve both
      user experience and the system's analytical capability. This protocol provides a
      detailed description of how to analyze genome-wide experimental data with the
      PANTHER classification system. 

PMID- 23868072
TI  - Relative and absolute determination of fluorescence quantum yields of transparent
      samples.
AB  - Luminescence techniques are among the most widely used detection methods in the
      life and material sciences. At the core of these methods is an ever-increasing
      variety of fluorescent reporters (i.e., simple dyes, fluorescent labels, probes,
      sensors and switches) from different fluorophore classes ranging from small
      organic dyes and metal ion complexes, quantum dots and upconversion nanocrystals
      to differently sized fluorophore-doped or fluorophore-labeled polymeric
      particles. A key parameter for fluorophore comparison is the fluorescence quantum
      yield (Phif), which is the direct measure for the efficiency of the conversion of
      absorbed light into emitted light. In this protocol, we describe procedures for
      relative and absolute determinations of Phif values of fluorophores in
      transparent solution using optical methods, and we address typical sources of
      uncertainty and fluorophore class-specific challenges. For relative
      determinations of Phif, the sample is analyzed using a conventional fluorescence
      spectrometer. For absolute determinations of Phif, a calibrated stand-alone
      integrating sphere setup is used. To reduce standard-related uncertainties for
      relative measurements, we introduce a series of eight candidate quantum yield
      standards for the wavelength region of ~350-950 nm, which we have assessed with
      commercial and custom-designed instrumentation. With these protocols and
      standards, uncertainties of 5-10% can be achieved within 2 h. 

PMID- 23868074
TI  - Generation of transgenic mice with megabase-sized human yeast artificial
      chromosomes by yeast spheroplast-embryonic stem cell fusion.
AB  - Introducing human genes into mice offers the opportunity to analyze their in vivo
      function or to obtain therapeutic molecules. For proper gene regulation, or in
      case of multigene families, megabase (Mb)-sized DNA fragments often have to be
      used. Yeast artificial chromosome (YAC)-mediated transgenesis is irreplaceable
      for this purpose, because alternative methods such as the use of bacterial
      artificial chromosomes (BACs) cannot introduce DNA fragments larger than 500 kb
      into the mouse germ line. However, YAC libraries often contain only partial gene
      loci. Time-consuming reconstruction of YACs, genetic instability and the
      difficulty in obtaining intact YAC DNA above a certain size impede the generation
      of humanized mice. Here we describe how to reconstruct YACs containing Mb-sized
      human DNA, such as the T cell receptor-alpha (TRA) gene locus, thus facilitating
      the introduction of large DNA fragments into the mouse germ line. Fusion of YAC
      containing yeast and embryonic stem (ES) cells avoids the need for YAC DNA
      purification. These ES cells are then used to stably introduce the functional TRA
      gene locus into the mouse germ line. The protocol takes ~1 year to complete, from
      reconstruction of the entire TRA gene locus from YACs containing partial but
      overlapping TRA regions to germline transmission of the YAC. 

PMID- 23868076
TI  - The C-terminal half of the alpha2C-adrenoceptor determines the receptor's
      membrane expression level and drug selectivity.
AB  - In tissues as well as in transfected cells, alpha2C-adrenoceptors show poorer
      expression levels compared to alpha2A-adrenoceptors. In order to characterize
      which regions of the alpha2C-adrenoceptor are involved in regulating the
      expression of binding-competent receptors at the plasma membrane, six chimeric
      alpha2A-/alpha2C-adrenoceptors were constructed. The wild-type alpha2A- and
      alpha2C-adrenoceptors and the six chimeric alpha2A-/alpha2C-adrenoceptors were
      transiently transfected into human embryonic kidney 293 (HEK293) cells, and the
      expression levels were investigated by radioligand binding. The results show that
      the C-terminal half of the alpha2C-adrenoceptor, ranging from the second
      extracellular loop to the C-terminus, is the main determinant of the low
      expression level of binding-competent alpha2C-adrenoceptors in HEK293 cell
      membranes. The so-called retention signal in the N-terminus of the alpha2C
      adrenoceptor had a less profound effect on the expression levels of the chimeric
      receptors. For seven drugs competing for [(3)H]-RX821002 binding, the K i values
      were determined at the wild-type alpha2A- and alpha2C-adrenoceptors and at four
      of the chimeric alpha2A-/alpha2C-adrenoceptors. The results show that the alpha2C
      over alpha2A-selectivity of spiroxatrine, spiperone, clozapine, MK912, and
      chlorpromazine, as well as the alpha2A- over alpha2C-selectivity of BRL44408,
      resides mainly in the C-terminal half of the receptors. To some extent, the
      region comprising the N-terminal half of the receptors contributed to the alpha2C
      selectivity of spiperone, clozapine, and chlorpromazine.

PMID- 23868077
TI  - Molecular epidemiology of norovirus in Singapore, 2004-2011.
AB  - Norovirus (NoV) is the most common cause of sporadic and epidemic
      gastroenteritis, globally. This study aimed to investigate the molecular
      epidemiology of NoV-associated acute gastroenteritis in Singapore by classifying
      circulating NoV genotypes and genogroup II, genotype 4 (GII.4) variants between
      September 2004 and February 2011. The temporal dominance and antigenic variation
      within the circulating epidemic NoV GII.4 variants was also examined, in order to
      compare the trends in Singapore to those observed globally during the same
      period. A total of 312 of 1,060 fecal specimens were positive for NoV RNA, using
      a quantitative RT-PCR. In a subset (125 of 312) of NoV positive samples, the 5'
      end of ORF2 (region C) of the GI or GII NoV genome was amplified and sequenced.
      Subsequent phylogenetic analysis identified GII.4 was the most commonly
      identified genotype representing 80.8% (101/125) of NoV sequenced in this study.
      The predominant GII.4 variants in circulation during the 2004-2011 epidemic
      periods were Hunter 2004 (2004-2005), Den Haag 2006b (2006-2009), and New Orleans
      2009 (2009-2011). Amino acid variation within the P2 domain of the major capsid
      protein, VP1, was followed longitudinally within the GII.4 lineage. A constant
      turnover of variant-specific amino acid change was observed, particularly within
      the antigenic epitopes A, C and E. In conclusion, this study has characterized
      the NoV strains in circulation in Singapore between 2004 and 2011. The molecular
      epidemiology and persistence of GII.4 pandemic NoV lineages in Singapore was
      similar to trends seen globally, with a noted absence of the Asia 2003 variant.

PMID- 23868078
TI  - Waardenburg syndrome: iris and choroidal hypopigmentation: findings on anterior
      and posterior segment imaging.
AB  - IMPORTANCE: Waardenburg syndrome typically manifests with congenital iris
      pigmentary abnormalities, but careful inspection can reveal additional posterior
      uveal pigmentary abnormalities. OBJECTIVE: To demonstrate iris and choroidal
      hypopigmentation in patients with Waardenburg syndrome. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective review of 7 patients referred for evaluation of
      presumed ocular melanocytosis. MAIN OUTCOMES AND MEASURES: To describe the
      clinical and imaging features of the anterior and posterior uvea. RESULTS: In all
      patients, the diagnosis of Waardenburg syndrome was established. The nonocular
      features included white forelock in 4 of 7 (57%), tubular nose in 5 of 6 (83%),
      and small nasal alae in 5 of 6 (83%) patients. In 2 patients, a hearing deficit
      was documented on audiology testing. Family history of Waardenburg syndrome was
      elicited in 5 of 7 (71%) patients. Ocular features (7 patients) included
      telecanthus in 5 (71%), synophrys in 2 (29%), iris hypopigmentation in 5 (71%),
      and choroidal hypopigmentation in 5 (71%) patients. No patient had muscle
      contractures or Hirschsprung disease. Visual acuity was 20/20 to 20/50 in all
      patients. Iris hypopigmentation in 8 eyes was sector in 6 (75%) and diffuse
      (complete) in 2 (25%). Choroidal hypopigmentation in 9 eyes (100%) showed a
      sector pattern in 6 (67%) and a diffuse pattern in 3 (33%). Anterior segment
      optical coherence tomography revealed the hypopigmented iris to be thinner and
      with shallower crypts than the normal iris. Posterior segment optical coherence
      tomography showed a normal retina in all patients, but the subfoveal choroid in
      the hypopigmented region was slightly thinner (mean, 197 MUm) compared with the
      opposite normal choroid (243 MUm). Fundus autofluorescence demonstrated mild
      hyperautofluorescence (scleral unmasking) in hypopigmented choroid and no
      lipofuscin abnormality. CONCLUSIONS AND RELEVANCE: Waardenburg syndrome manifests
      hypopigmentation of the iris and choroid with imaging features showing a slight
      reduction in the thickness of the affected tissue.

PMID- 23868079
TI  - The influence of genetic explanations of type 2 diabetes on patients' attitudes
      to prevention, treatment and personal responsibility for health.
AB  - BACKGROUND/AIMS: It is widely accepted that type 2 diabetes is caused by an
      interaction of both lifestyle and genetic factors. However, the impact of
      explaining disease aetiology as primarily genetic or environmental is relatively
      unexplored for common chronic multi-factorial conditions. This study investigates
      whether perceiving the cause of type 2 diabetes as primarily genetic or
      environmental influences attitudes towards the controllability of the condition.
      METHODS: Using a between-participants vignette-based experimental survey design,
      200 participants aged 40 years and above from a primary care setting responded to
      a vignette which implied the cause of diabetes as being predominantly genetic or
      environmental. Attitudes towards personal responsibility, prevention and
      treatment were measured using an attitude questionnaire. RESULTS: There was a
      significant interaction effect between perceived aetiology and family history on
      attitude to treatment; participants with a family history of type 2 diabetes
      perceived treatment as less effective if they read the genetic vignette, but
      those without a family history did not (p < 0.05). The findings also indicated
      that an individual was perceived as less responsible for the development of type
      2 diabetes (p < 0.05) when participants (regardless of family history) read a
      vignette with an implied genetic causation. CONCLUSION: Awareness by health
      professionals of the impact of genetic attributions in disease aetiology is
      fundamental when encouraging positive attitudes to personal responsibility for
      lifestyle change and treatment for the condition. These findings may impact the
      way preventative health messages are tailored to people depending on their family
      history of diabetes.

PMID- 23868080
TI  - Normal grief and complicated bereavement among traumatized Cambodian refugees:
      cultural context and the central role of dreams of the dead.
AB  - This article profiles bereavement among traumatized Cambodian refugees and
      explores the validity of a model of how grief and post-traumatic stress disorder
      (PTSD) interact in this group to form a unique bereavement ontology, a model in
      which dreams of the dead play a crucial role. Several studies were conducted at a
      psychiatric clinic treating Cambodian refugees who survived the Pol Pot genocide.
      Key findings included that Pol Pot deaths were made even more deeply disturbing
      owing to cultural ideas about "bad death" and the consequences of not performing
      mortuary rites; that pained recall of the dead in the last month was common (76 %
      of patients) and usually caused great emotional and somatic distress; that
      severity of pained recall of the dead was strongly associated with PTSD severity
      (r = .62); that pained recall was very often triggered by dreaming about the
      dead, usually of someone who died in the Pol Pot period; and that Cambodians have
      a complex system of interpretation of dreams of the deceased that frequently
      causes those dreams to give rise to great distress. Cases are provided that
      further illustrate the centrality of dreams of the dead in the Cambodian
      experiencing of grief and PTSD. The article shows that not assessing dreams and
      concerns about the spiritual status of the deceased in the evaluation of
      bereavement results in "category truncation," i.e., a lack of content validity, a
      form of category fallacy.

PMID- 23868081
TI  - Division of primary care services between physicians, physician assistants, and
      nurse practitioners for older patients with diabetes.
AB  - Team-based care involving physician assistants and/or nurse practitioners
      (PA/NPs) in the patient-centered medical home is one approach to improving care
      quality. However, little is known about how to incorporate PA/NPs into primary
      care teams. Using data from a large physician group, we describe the division of
      patients and services (e.g., acute, chronic, preventive, other) between primary
      care providers for older diabetes patients on panels with varying levels of PA/NP
      involvement (i.e., no role, supplemental provider, or usual provider of care).
      Panels with PA/NP usual providers had higher proportions of patients with
      Medicaid, disability, and depression. Patients with physician usual providers had
      similar probabilities of visits with supplemental PA/NPs and physicians for all
      service types. However, patients with PA/NP usual providers had higher
      probabilities of visits with a supplemental physician. Understanding how patients
      and services are divided between PA/NPs and physicians will assist in defining
      provider roles on primary care teams.

PMID- 23868082
TI  - The continuity and quality of primary care.
AB  - Patients who have access to different health care systems, such as Medicare
      eligible veterans, may obtain services in either or both health systems. We
      examined whether quality of diabetes care was associated with care continuity or
      veterans' usual source of primary care in a retrospective cohort study of 1,867
      Medicare-eligible veterans with diabetes in 2001 to 2004. Underprovision of
      quality of diabetes care was more common than overprovision. In adjusted
      analyses, veterans who relied only on Medicare fee-for-service (FFS) for primary
      care were more likely to be underprovided HbA1c testing than veterans who relied
      only on Veteran Affairs (VA) for primary care. Dual users of VA and Medicare FFS
      primary care were significantly more likely to be overprovided HbA1c and
      microalbumin testing than VA-only users. VA and Medicare providers may need to
      coordinate more effectively to ensure appropriate diabetes care to Medicare
      eligible veterans, because VA reliance was a stronger predictor than care
      continuity.

PMID- 23868084
TI  - Angiotensin-converting-enzyme inhibition counteracts angiotensin II-mediated
      endothelial cell dysfunction by modulating the p38/SirT1 axis.
AB  - OBJECTIVE: Oxidative stress has been linked to endothelial dysfunction and
      angiotensin II stimulates the reactive oxygen species production contributing to
      several cardiovascular diseases. We have studied the chain of events induced by
      angiotensin-converting-enzyme (ACE) activation in vascular umbilical vein
      endothelial cells (HUVECs) by using an ACE inhibitor such as zofenoprilat.
      METHODS: We used specific assay to measure the superoxide anion production,
      tetrazolium bromide (MTT) assay for cell viability, terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) assay for cell apoptosis, and
      western blot for protein analysis in the study. RESULTS: Zofenoprilat counteracts
      the superoxide anion production and cell apoptosis induced by angiotensin I
      treatment by blocking the extrinsic caspase cascade, NF-kB and p38 activation.
      p38 inhibitor SB203580 reverted the angiotensin II oxidant effects while the p38
      constitutively activation, by MKK6 transfection, abrogated the zofenoprilat
      effects. Characterizing the zofenoprilat downstream effector we found that
      zofenoprilat reverted the SirT-1 downregulation induced by angiotensin II. p38
      activation by angiotensin II was strictly correlated with SirT1 protein
      downregulation; SB203580 significantly prevented SirT1 downregulation induced by
      angiotensin II while the p38 constitutive activation abolished SIRT1 protein
      basal levels. p38 directly bound SirT1 sequestering it in the cytoplasm. SirT1
      inhibition by sirtinol annulled zofenoprilat action while SirT1 overexpression
      reverted the cytotoxic effects of angiotensin II. Finally, zofenoprilat
      negatively controlled angiotensin I receptor protein expression through SirT1.
      CONCLUSION: The p38-SirT1 axis is found markedly relevant in modulating the
      cardiovascular benefit deriving from ACE-inhibitors and might represent a novel
      target for innovative drugs in cardiovascular prevention.

PMID- 23868083
TI  - The impact of variability in ultrasound settings on the measured echolucency of
      the carotid intima-media.
AB  - BACKGROUND: B-mode ultrasound measurements of the echolucency of the carotid
      intima-media may hold information on cardiovascular risk. The information
      obtained from this measurement may depend on which gain settings are used. We
      studied the effect of gain settings on echolucency measurements and its
      consequences on risk factor relations and treatment effects. METHODS: We used two
      approaches. In the first, we examined the relationship between calibration, gain
      and common grey-scale median (GSM) from repeated ultrasound images obtained from
      four healthy individuals at gain settings ranging from -20 to 20 dB. In the
      second, we evaluated the effect of gain settings on the relation of risk factors
      and statin treatment with common GSM, using images from 325 participants of the
      Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin
      (METEOR) study with documented gain settings. Echolucency of the carotid intima
      media was measured from ultrasound images using PaintShop Pro and Artery
      Measurement Software and expressed as GSM. RESULTS: In healthy individuals,
      common GSM increased with increments in gain setting, primarily when the
      measurements were not calibrated. In the METEOR study sample, age and sex were
      significantly related to gain setting. The risk factor relations with common GSM
      were of the same magnitude and direction after adjustment for gain setting.
      Furthermore, adjustment for gain setting did not alter the rates of GSM change
      over time. CONCLUSION: Extreme variability in gain settings has a major impact on
      the echolucency measurements of the far wall common carotid intima-media.
      Calibration should be used to adjust for these effects of gain settings.
      Variability in gain settings, however, seems limited in real practice and did not
      change the direction and magnitude of the relations under study. However, as age
      and sex are major determinants of gain settings, adjustment for or stratification
      by age and sex is recommended in studies into echolucency of the carotid intima
      media in situations in which gain settings are unknown.

PMID- 23868085
TI  - The influence of high versus low sodium intake on blood pressure and
      haemodynamics in patients with morbid obesity.
AB  - BACKGROUND: Many patients with morbid obesity (BMI > 40 kg/m) have hypertension.
      The complex pathophysiological abnormalities linking hypertension to obesity have
      not been fully clarified, but abnormal sodium handling could be an important
      mechanism. METHOD: Therefore, we examined changes in body fluid compartments and
      haemodynamic responses (at rest and during exercise) after 5 days of a low-sodium
      diet (90 mmol/day) and 5 days of a high-sodium diet (250 mmol/day) in 12 morbidly
      obese, hypertensive patients; 12 morbidly obese, normotensive patients and 12
      nonobese controls. RESULTS: High sodium intake as compared to low sodium intake
      was associated with an increase in plasma volume (obese, hypertensive patients: 5
      +/- 4%; obese, normotensive patients: 10 +/- 11%; nonobese controls: 7 +/- 6%),
      cardiac output (CO) (obese, hypertensive patients: 17 +/- 12%; obese,
      normotensive patients: 20 +/- 16%; nonobese controls: 13 +/- 14%) and stroke
      volume (SV) (obese, hypertensive patients: 27 +/- 26%; obese, normotensive
      patients: 27 +/- 24%; nonobese controls: 18 +/- 27%) in all three groups with no
      differences between the groups. Despite an increase in CO during high salt
      intake, 24-h blood pressure (BP) was unchanged in patients and controls as a
      result of a reduction in total peripheral resistance (obese, hypertensive
      patients: -11 +/- 11%; obese, normotensive patients: -10 +/- 12%; nonobese
      controls: -5 +/- 14%). Similar changes were observed during an incremental
      bicycle exercise test wherein CO and SV were higher, whereas mean arterial BP was
      unchanged at each exercise level during high sodium intake. CONCLUSION: Despite
      substantial increases in CO and SV, we did not observe any significant change in
      BP during high sodium intake, neither in morbid obese patients nor in lean
      individuals.

PMID- 23868086
TI  - Inflammatory mediators in saliva associated with arterial stiffness and
      subclinical atherosclerosis.
AB  - OBJECTIVE: Whereas circulating levels of C-reactive protein (CRP) have been
      associated with, for example, arterial stiffness, subclinical atherosclerosis and
      metabolic syndrome, other inflammatory biomarkers with potential interest for
      these conditions may not be measurable systemically. The predictive value of
      salivary biomarkers in these contexts has remained largely unexplored. The aim of
      the present study was to establish the association of different salivary
      biomarkers of inflammation with subclinical cardiovascular disease. METHODS: Two
      hundred and fifty-nine individuals were included in the study. Saliva and plasma
      samples were collected, and each individual underwent carotid ultrasound and
      measures of pulse wave velocity and blood pressure. Medical history of previous
      cardiovascular disease, current medications and smoking were collected by
      questionnaire. RESULTS: Salivary levels of CRP, leukotriene B4 (LTB4),
      prostaglandin E2 (PGE2), matrix metalloproteinase 9 (MMP-9), creatinine and
      lysozyme were measured. Salivary levels of CRP were significantly correlated with
      plasma levels (r = 0.73, P < 0.0001). In an age-adjusted and sex-adjusted
      analysis, salivary CRP was significantly and positively correlated with mean
      arterial blood pressure, pulse pressure, pulse wave velocity, BMI, metabolic
      syndrome, waist-to-hip ratio and intima-media thickness. Increasing age and sex
      adjusted salivary CRP tertiles were in addition associated with carotid plaques.
      In a multivariate analysis, CRP and MMP-9 were associated with intima-media
      thickness, LTB4 and PGE2 with arterial stiffness, and lysozyme with hypertension.
      CONCLUSION: Saliva may represent an alternative mean for evaluation of
      cardiovascular risk.

PMID- 23868087
TI  - Association of central pulse pressure with contrast-induced nephropathy and
      clinical outcomes in patients undergoing coronary intervention.
AB  - OBJECTIVE: The increase in pulse pressure (PP) may be transmitted to the
      glomerulus and thus impair renal blood flow autoregulation. This subtle change
      could predispose patients to the detrimental effect of contrast media. We sought
      to determine whether elevated central PP is associated with increased contrast
      induced nephropathy (CIN) and future cardiovascular events in patients undergoing
      percutaneous coronary intervention (PCI). METHODS: In total, 448 consecutive
      patients receiving PCI were enrolled. In each patient, central and peripheral
      blood pressures were measured before PCI. The occurrence of CIN was identified
      and defined as a rise in serum creatinine of 0.5 mg/dl or a 25% increase from the
      baseline value within 48 h after the procedure. All patients were then followed
      up for at least 3 years or until the occurrence of a major adverse cardiovascular
      event (MACE) including death, nonfatal myocardial infarction, and ischemic stroke
      after coronary intervention. RESULTS: Overall, CIN occurred in 52 (11.6%)
      patients. Patients developing CIN had higher baseline central PP (P = 0.004).
      Patients were then stratified into three groups (low/intermediate/high) according
      to baseline central PP. Compared to that with the lowest tertile of central PP,
      patients with the highest tertile of central PP had a significantly increased
      incidence of CIN after PCI (odds ratio, 2.94; 95% confidence interval, CI 1.02
      8.51). By Cox regression analysis, elevated central PP was an independent
      predictor of future MACE in all patients undergoing PCI (hazard ratio, 2.07; 95%
      CI 1.04-4.12). CONCLUSION: Elevated baseline central PP was associated with an
      increased risk of CIN and future cardiovascular events in patients with PCI.
      Further clinical study may be indicated to determine whether pharmacological
      modulation on baseline central PP could prevent CIN and future MACE after PCI.

PMID- 23868088
TI  - Dissecting the genetic predisposition to albuminuria and endothelial dysfunction
      in a genetic rat model.
AB  - OBJECTIVE: The Munich Wistar Fromter (MWF) rat develops progressive spontaneous
      albuminuria largely attributable to quantitative trait loci on rat chromosome
      (RNO)6 and RNO8, respectively. We tested the hypothesis whether quantitative
      trait loci on these chromosomes are linked to both albuminuria and endothelial
      dysfunction. METHODS: Experiments were performed in male 12-week-old MWF, Wistar
      Kyoto (WKY), spontaneously hypertensive rat (SHR) and consomic MWF-6 and MWF-8
      rats, in which RNO6 or RNO8 was replaced by the respective SHR chromosome (n = 10
      per strain). Vascular function was assessed in aorta and vascular superoxide
      anion production was determined by confocal microscopy. RESULTS: Acetylcholine
      potency to induce relaxation was significantly reduced in MWF (6.2 +/- 0.1)
      compared with WKY (7.1 +/- 0.1) or SHR (7.3 +/- 0.1; P < 0.01). N-nitro-L
      arginine methyl ester abolished relaxation to acetylcholine in all three strains,
      whereas indomethacin exhibited no effect in WKY and MWF. Contractions to
      noradrenaline and superoxide production were significantly higher in MWF compared
      with SHR and WKY (P < 0.05, respectively). In consomic MWF-6 and MWF-8 rats
      albuminuria was markedly suppressed (-85 and -92%, P < 0.005 compared with MWF,
      respectively). Interestingly, relaxation to acetylcholine and contraction to
      noradrenaline were restored to normal WKY levels only in MWF-8, but not in MWF-6,
      due to an increase in stimulated and basal nitric oxide availability,
      respectively. CONCLUSION: These data demonstrate the partial genetic independence
      of albuminuria and endothelial dysfunction in this model. From two known
      albuminuria quantitative trait loci one locus affects both albuminuria and
      endothelial dysfunction. Whether this observation is based on a common genetic
      mechanism related to NO availability warrants further investigation.

PMID- 23868089
TI  - Evidence of direct complementary interactions between messenger RNAs and their
      cognate proteins.
AB  - Recently, the ability to interact with messenger RNA (mRNA) has been reported for
      a number of known RNA-binding proteins, but surprisingly also for different
      proteins without recognizable RNA binding domains including several transcription
      factors and metabolic enzymes. Moreover, direct binding to cognate mRNAs has been
      detected for multiple proteins, thus creating a strong impetus to search for
      functional significance and basic physico-chemical principles behind such
      interactions. Here, we derive interaction preferences between amino acids and RNA
      bases by analyzing binding interfaces in the known 3D structures of protein-RNA
      complexes. By applying this tool to human proteome, we reveal statistically
      significant matching between the composition of mRNA sequences and base-binding
      preferences of protein sequences they code for. For example, purine density
      profiles of mRNA sequences mirror guanine affinity profiles of cognate protein
      sequences with quantitative accuracy (median Pearson correlation coefficient R = 
      0.80 across the entire human proteome). Notably, statistically significant anti
      matching is seen only in the case of adenine. Our results provide strong evidence
      for the stereo-chemical foundation of the genetic code and suggest that mRNAs and
      cognate proteins may in general be directly complementary to each other and
      associate, especially if unstructured. 

PMID- 23868090
TI  - Early steps of active DNA demethylation initiated by ROS1 glycosylase require
      three putative helix-invading residues.
AB  - Active DNA demethylation is crucial for epigenetic control, but the underlying
      enzymatic mechanisms are incompletely understood. REPRESSOR OF SILENCING 1 (ROS1)
      is a 5-methylcytosine (5-meC) DNA glycosylase/lyase that initiates DNA
      demethylation in plants through a base excision repair process. The enzyme binds
      DNA nonspecifically and slides along the substrate in search of 5-meC. In this
      work, we have used homology modelling and biochemical analysis to gain insight
      into the mechanism of target location and recognition by ROS1. We have found that
      three putative helix-intercalating residues (Q607, R903 and M905) are required
      for processing of 5-meC:G pairs, but dispensable for excision of mismatched 5
      meC. Mutant proteins Q607A, R903A and M905G retain the capacity to process an
      abasic site opposite G, thus suggesting that all three residues play a critical
      role in early steps of the base extrusion process and likely contribute to
      destabilization of 5-meC:G pairs. While R903 and M905 are not essential for DNA
      binding, mutation of Q607 abrogates stable binding to both methylated and
      nonmethylated DNA. However, the mutant protein Q607A can form stable complexes
      with DNA substrates containing blocked ends, which suggests that Q607
      intercalates into the helix and inhibits sliding. Altogether, our results suggest
      that ROS1 uses three predicted helix-invading residues to actively interrogate
      DNA in search for 5-meC. 

PMID- 23868091
TI  - The cumulative risk of false-positive fecal occult blood test after 10 years of
      colorectal cancer screening.
AB  - BACKGROUND: Annual colorectal cancer screening with fecal occult blood test
      (FOBT) is a noninvasive alternative to screening colonoscopy once every 10 years.
      If false-positive FOBT results are common, then many patients selecting an FOBT
      regimen will be exposed to the same invasive testing as those selecting a
      colonoscopy regimen. The objective of this study was to estimate the probability
      of experiencing a false-positive after receiving annual FOBT screening for 10
      years. METHODS: Medical records for patients aged 50 to 79 years receiving FOBT
      screening with Hemoccult Sensa between 1997 and 2009 at Group Health of
      Washington State captured the date and results of each FOBT, along with
      subsequent colorectal cancer diagnoses. We used logistic regression to analyze
      associations between patient characteristics and odds of a positive FOBT with no
      invasive cancer diagnosis within 1 year (FOBT+, CRC-). We estimated the
      probability of receiving at least one FOBT+, CRC- result after 10 years of
      screening. RESULTS: We observed 181,950 FOBTs from 94,637 individuals. Older
      patients, males, and non-White patients were significantly more likely to receive
      FOBT+, CRC- results (P < 0.001 for all risk factors). After 10 years of annual
      FOBT, 23.0% [95% confidence interval (CI), 18.2-27.0] will receive at least one
      FOBT+, CRC- result. CONCLUSIONS: Most patients participating in annual FOBT
      screening for 10 years will not have a positive result, reinforcing the potential
      value of this regimen as a noninvasive alternative to colonoscopy. IMPACT: Annual
      stool-based screening is a screening alternative resulting in substantially fewer
      colonoscopies than once per decade colonoscopy.

PMID- 23868092
TI  - Mild cognitive impairment in Parkinson's disease.
AB  - The concept of mild cognitive impairment (MCI) in the general population has
      received increased attention over recent years, and is associated with risk of
      progression to Alzheimer's disease. Within Parkinson's disease (PD), MCI (PD-MCI)
      is also now recognised to be relatively common, with certain subtypes predicting
      progression to Parkinson's disease dementia (PDD). Recently, criteria to better
      characterise PD-MCI and its subtypes have been produced by the Movement Disorder
      Society. In contrast to the population as a whole, where amnestic MCI is the most
      common subtype, non-amnestic PD-MCI dominates, with prominent executive and
      attention dysfunction. Although the pathophysiology of PD-MCI is poorly
      understood and encompasses both PD and non-PD pathology, it is most likely the
      result of a complex interaction between neurotransmitter dysfunction, synaptic
      pathology, protein aggregation and neuronal damage. Determining the factors that
      influence the progression of these pathologies in PD and the individuals at risk
      of ultimately developing PDD is critical for targeted intervention and drug
      discovery studies. Further work is required, however, to determine the
      significance of PD-MCI and also to validate the diagnostic criteria. This would
      be best delivered in the form of longitudinal studies in homogenous cohorts of PD
      participants, to allow prognostication and generalisation among the PD
      population. At the present time, no drug therapies are available for PD-MCI.
      Management includes screening for the disorder, excluding treatable causes of
      cognitive decline and cautious use of dopamine agonists and medications such as
      anticholinergics.

PMID- 23868093
TI  - Pilot cluster randomised controlled trial of flooring to reduce injuries from
      falls in wards for older people.
AB  - BACKGROUND: falls disproportionately affect older people, who are at increased
      risk of falls and injury. This pilot study investigates shock-absorbing flooring
      for fall-related injuries in wards for frail older people. METHODS: we conducted
      a non-blinded cluster randomised trial in eight hospitals in England between
      April 2010 and August 2011. Each site allocated one bay as the 'study area',
      which was randomised via computer to intervention (8.3-mm thick Tarkett
      Omnisports EXCEL) or control (2-mm standard in situ flooring). Sites had an
      intervention period of 1 year. Anybody admitted to the study area was eligible.
      The primary outcome was the fall-related injury rate. Secondary outcomes were
      injury severity, fall rate and adverse events. RESULTS: during the intervention
      period, 226 participants were recruited to each group (219 and 223 were analysed
      in the intervention and control group, respectively). Of 35 falls (31 fallers) in
      the intervention group, 22.9% were injurious, compared with 42.4% of 33 falls (22
      fallers) in the control group [injury incident rate ratio (IRR) = 0.58, 95% CI =
      0.18-1.91]. There were no moderate or major injuries in the intervention group
      and six in the control group. The fall IRR was 1.07 (95% CI = 0.64-1.81). Staff
      at intervention sites raised concerns about pushing equipment, documenting one
      pulled back. CONCLUSIONS: future research should assess shock-absorbing flooring
      with better 'push/pull' properties and explore increased faller risk. We estimate
      a future trial will need 33,480-52,840 person bed-days per arm.

PMID- 23868094
TI  - Characterization of exudates released by the marine diatom Skeletonema costatum
      exposed to copper stress: a 3D-fluorescence spectroscopy approach.
AB  - In a laboratory study, metal contamination experiments were conducted to
      investigate the effects of two free copper concentrations (10(-9) and 10(-8) M)
      on cell growth and on dissolved organic matter exudation by a marine diatom
      Skeletonema costatum. Throughout incubation, the growth kinetics and exudation of
      extracellular molecules (i.e. dissolved organic carbon (DOC) and the fluorescent
      organic matter) were determined. Results revealed an inhibition of S. costatum
      growth when the free copper level increased (from 10(-9) to 10(-8)). Furthermore,
      DOC release was more significant in cultures contaminated by 10(-9) M Cu(2+) than
      in control, suggesting a coping mechanism developed by this species. In this
      study, samples were daily analysed by 3D-fluorescence and PARAFAC algorithm, in
      order to compare the fluorescent material produced during growth under different
      contaminations. PARAFAC treatment revealed two main contributions: one related to
      the biological activity (C1), the other linked to the marine organic matter (C2).
      The third component C3 was typically protein-like. This fluorophore was
      considered as a tryptophan-like fluorophore, whereas the C1 and the C2 components
      were associated to marine production such as humic matter.

PMID- 23868095
TI  - Disclosing and overcoming the trade-off between noise and scanning speed in
      atomic force microscopy.
AB  - Traditional dynamic modalities for atomic force microscopy imaging suffer from a
      stringent trade-off between fast scanning speed, weak interaction forces and
      accurate topography reconstruction. Finding an effective compromise between these
      aspects is often challenging, especially for soft biological samples for which
      stringent requirements hold when imaged in vivo. In this paper the main causes of
      this undesired trade-off in standard systems are analyzed and the exploitation of
      the intrinsic dynamics of the cantilever through a nonlinear control strategy is
      proposed as a method to overcome this limitation. A direct application to imaging
      of biological samples is reported to validate the results and show the
      effectiveness of the proposed technique.

PMID- 23868096
TI  - Long term behavior of biological prostheses used as abdominal wall substitutes.
AB  - BACKGROUND: Despite their degradation in the host organism, the benefits of
      collagen bioprostheses remain unclear. This study addresses the absorption and
      long-term host tissue incorporation of several collagen biomeshes. MATERIAL AND
      METHODS: Partial ventral hernial defects created in the abdominal wall of rabbits
      were repaired using the crosslinked meshes Permacol(r) or CollaMend(r), or the
      non-crosslinked Surgisis(r), Tutomesh(r) or Strattice(r). After 90 and 180 days
      of implant, morphological studies and morphometric analysis of the thickness of
      the meshes were performed. Immunofluorescence confocal microscopy combined with
      differential interference contrast (DIC) imaging was used to distinguish newly
      formed collagen from that comprising the mesh. The macrophage response was
      examined by immunohistochemistry. RESULTS: At 90 days, the thinner non
      crosslinked biomeshes Tutomesh and Surgisis were more fully degraded with much of
      their collagen replaced with loose connective tissue. By 180 days, both implants
      had been practically fully absorbed. In contrast, in Strattice only the outermost
      third was infiltrated by neoformed tissue. On both surfaces of the crosslinked
      meshes, a fibrous capsule with host cells lining its perimeter was observed at
      both time points, though at 180 days these cells had penetrated the mesh
      interior. At both implant times, Strattice showed the higher expression of
      collagen type I while collagen III expression was similar for all the meshes. The
      non-crosslinked materials elicited lower macrophage counts at both time points,
      significantly so for Strattice. The macrophage response decreased over time for
      all the meshes but Surgisis. CONCLUSIONS: Strattice, the thicker, more compacted
      non-crosslinked mesh showed the best balance between tissue incorporation and
      absorption while eliciting a minimal foreign-body reaction in the long-term.

PMID- 23868097
TI  - Adult diffuse hepatic hemangiomatosis: a rare cause of dilated cardiomyopathy and
      sudden cardiac arrest.

PMID- 23868098
TI  - Indoor tanning amongst young adults: time to stop sleeping on the banning of
      sunbeds.

PMID- 23868099
TI  - Zinc at sub-cytotoxic concentrations induces heme oxygenase-1 expression in human
      cancer cells.
AB  - BACKGROUND/AIMS: This study investigated the effects of zinc on heme oxygenase-1
      (HO-1) expression in human cancer cells. METHODS/RESULTS: Zinc at sub-cytotoxic
      concentrations (50-100 MUM) induces HO-1 expression in the MDA-MB-231 (human
      breast cancer) and A2780 (human ovarian cancer) cell lines in a concentration-
      and time-dependent manner. The induction of HO-1 by zinc was detected after 4-6
      hours of treatment, reached maximal level at 8 hours, and declined thereafter.
      Using a human HO-1 gene promoter reporter construct, we identified two
      antioxidant response elements (AREs) that mediated the zinc-induced increase in
      HO-1 gene transcription, indicating that the nuclear factor (erythroid-derived 2)
      like 2 (Nrf2) signaling pathway is involved in this event. This assumption was
      supported by the observations that knockdown of Nrf2 expression compromised the
      zinc-induced increase in HO-1 gene transcription, and that zinc increased Nrf2
      protein expression and the Nrf2 binding to the AREs. Additionally, we found that
      the zinc-induced HO-1 gene transcription can be enhanced by clioquinol, a zinc
      ionophore, and reversed by pretreatment with TPEN, a known zinc chelator,
      indicating that an increase in intracellular zinc levels is responsible for this
      induction. CONCLUSION: These findings demonstrate that zinc at sub-cytotoxic
      concentrations induces HO-1 expression in human cancer cells. The biological
      significance of this induction merits further investigation.

PMID- 23868100
TI  - Modeling of oxidized PTH (oxPTH) and non-oxidized PTH (n-oxPTH) receptor binding
      and relationship of oxidized to non-oxidized PTH in children with chronic renal
      failure, adult patients on hemodialysis and kidney transplant recipients.
AB  - BACKGROUND: The biological properties of oxidized and non-oxidized PTH are
      substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating
      properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor.
      This was described in more than 20 well published studies in the 1970(s) and
      80(s). However, PTH oxidation has been ignored during the development of PTH
      assays for clinical use so far. Even the nowadays used third generation assay
      systems do not consider oxidation of PTH We recently developed an assay to
      differentiate between oxPTH and n-oxPTH. In the current study we established
      normal values for this assay system. Furthermore, we compare the ratio of oxPTH
      to n-oxPTH in different population with chronic renal failure: 620 children with
      renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602
      kidney transplant recipients. In addition, we performed modeling of the
      interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical
      structure approaches. RESULTS: The children had the highest mean as well as
      maximum n-oxPTH concentrations as compared to adult patients (both patients on
      dialysis as well as kidney transplant recipients). The relationship between oxPTH
      and n-oxPTH of individual patients varied substantially in all three populations
      with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects
      revealed that n-oxPTH concentrations in patient with renal failure were higher as
      compared to healthy adult controls (2.25-fold in children with renal failure,
      1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant
      recipients, respectively). Computer assisted biophysical structure modeling
      demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and
      n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence
      alters PTH-PTH receptor interaction via oxidation induced three-dimensional
      structure alteration of PTH. CONCLUSION: A huge proportion of circulating PTH
      measured by current state-of-the-art assay systems is oxidized and thus not
      biologically active. The relationship between oxPTH and n-oxPTH of individual
      patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25
      fold higher in patients with renal failure as compared to health controls.
      Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH
      measures describes most likely oxidative stress in patients with renal failure
      rather than the PTH hormone status. This, however, needs to be demonstrated in
      further clinical studies. (c) 2013 S. Karger AG, Basel.

PMID- 23868101
TI  - HSV-NIS, an oncolytic herpes simplex virus type 1 encoding human sodium iodide
      symporter for preclinical prostate cancer radiovirotherapy.
AB  - Several clinical trials have shown that oncolytic herpes simplex virus type 1
      (oHSV-1) can be safely administered to patients. However, virus replication in
      tumor tissue has generally not been monitored in these oHSV clinical trials, and
      the data suggest that its oncolytic potency needs to be improved. To facilitate
      noninvasive monitoring of the in vivo spread of an oHSV and to increase its
      antitumor efficacy, the gene coding for human sodium iodide symporter (NIS) was
      incorporated into a recombinant oHSV genome and the corresponding virus (oHSV
      NIS) rescued in our laboratory. Our data demonstrate that a human prostate cancer
      cell line, LNCap, efficiently concentrates radioactive iodine after the cells
      have been infected in vitro or in vivo. In vivo replication of oHSV-NIS in tumors
      was noninvasively monitored by computed tomography/single-photon emission
      computed tomography imaging of the biodistribution of pertechnetate and was
      confirmed. LNCap xenografts in nude mice were eradicated by intratumoral
      administration of oHSV-NIS. Systemic administration of oHSV-NIS prolonged the
      survival of tumor-bearing mice, and the therapeutic effect was further enhanced
      by administration of (131)I after the intratumoral spread of the virus had
      peaked. oHSV-NIS has the potential to substantially enhance the outcomes of
      standard therapy for patients with prostate cancer.

PMID- 23868102
TI  - Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal
      osteoporosis in the US.
AB  - BACKGROUND: In the US, 26 % of women aged >=65 years, and over 50 % of women aged
      >=85 years are affected with postmenopausal osteoporosis (PMO). Each year, the
      total direct health care costs are estimated to be $US12-18 billion. OBJECTIVE:
      The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal
      osteoporotic women from a US third-party payer perspective was evaluated.
      METHODS: A lifetime cohort Markov model was developed with seven health states:
      'well', hip fracture, vertebral fracture, 'other' osteoporotic fracture, post-hip
      fracture, post-vertebral fracture, and dead. During each cycle, patients could
      have a fracture, remain healthy, remain in a post-fracture state or die. Relative
      fracture risk reductions, background fracture risks, mortality rates, treatment
      specific persistence rate, utilities, and medical and drug costs were derived
      using published sources. Expected costs and quality-adjusted life years (QALYs)
      were estimated for generic alendronate, denosumab, branded risedronate, and
      branded ibandronate in the overall PMO population and high-risk subgroups: (a)
      >=2 of the following risks: >70 years of age, bone mineral density (BMD) T score
      less than or equal to -3.0, and prevalent vertebral fracture; and (b) >=75 years
      of age. Costs and QALYs were discounted at 3 % annually, and all costs were
      inflated to 2012 US dollars. Sensitivity analyses were conducted by varying
      parameters e.g., efficacies of interventions, costs, utilities, and the
      medication persistence ratio. RESULTS: In the overall PMO population, total
      lifetime costs for alendronate, denosumab, risedronate, and ibandronate were
      $US64,400, $US67,400, $US67,600 and $US69,200, respectively. Total QALYs were
      8.2804, 8.3155, 8.2735 and 8.2691, respectively. The incremental cost
      effectiveness ratio (ICER) for denosumab versus generic alendronate was
      $US85,100/QALY. Risedronate and ibandronate were dominated by denosumab. In the
      high-risk subgroup (a), total costs for alendronate, denosumab, risedronate and
      ibandronate were $US70,400, $US70,800, $US74,000 and $US76,900, respectively.
      Total QALYs were 7.2006, 7.2497, 7.1969 and 7.1841, respectively. Denosumab had
      an ICER of $US7,900/QALY versus generic alendronate and dominated all other
      strategies. Denosumab dominated all strategies in women aged >=75 years. Base
      case results between denosumab and generic alendronate were most sensitive to the
      relative risk of hip fracture for both drugs and the cost of denosumab.
      CONCLUSION: In each PMO population examined, denosumab represented good value for
      money compared with branded bisphosphonates. Furthermore, denosumab was either
      cost effective or dominant compared with generic alendronate in the high-risk
      subgroups.

PMID- 23868103
TI  - Subjective health complaints and self-rated health: are expectancies more
      important than socioeconomic status and workload?
AB  - BACKGROUND: The associations between socioeconomic status (SES), physical and
      psychosocial workload and health are well documented. According to The Cognitive
      Activation Theory of Stress (CATS), learned response outcome expectancies
      (coping, helplessness, and hopelessness) are also important contributors to
      health. This is in part as independent factors for health, but coping may also
      function as a buffer against the impact different demands have on health.
      PURPOSE: The purpose of this study was to investigate the relative effect of SES
      (as measured by level of education), physical workload, and response outcome
      expectancies on subjective health complaints (SHC) and self-rated health, and if
      response outcome expectancies mediate the effects of education and physical
      workload on SHC and self-rated health. METHODS: A survey was carried out among
      1,746 Norwegian municipal employees (mean age 44.2, 81 % females). Structural
      Equation Models with SHC and self-rated health as outcomes were conducted.
      Education, physical workload, and response outcome expectancies, were the
      independent 28 variables in the model. RESULTS: Helplessness/hopelessness had a
      stronger direct effect on self-rated health and SHC than education and physical
      workload, for both men and women. Helplessness/hopelessness fully mediated the
      effect of physical workload on SHC for men (0.121), and mediated 30 % of a total
      effect of 0.247 for women. For women, education had a small but significant
      indirect effect through helplessness/hopelessness on self-rated health (0.040)
      and SHC (-0.040), but no direct effects were found. For men, there was no effect
      of education on SHC, and only a direct effect on self-rated health (0.134).
      CONCLUSIONS: The results indicated that helplessness/hopelessness is more
      important for SHC and health than well-established measures on SES such as years
      of education and perceived physical workload in this sample.
      Helplessness/hopelessness seems to function as a mechanism between physical
      workload and health.

PMID- 23868104
TI  - Preparation and luminescence properties of Ce3+ and Ce3+/Tb(3+)-activated
      Y4Si2O7N2 phosphors.
AB  - Ce(3+) and Ce(3+)/Tb(3+)-activated Y4Si2O7N2 phosphors are synthesized by the
      solid-state method, which can be efficiently excited by near ultraviolet (UV)
      light emitting diode (LED) chips. The PL spectrum of Y4Si2O7N2:Ce(3+) shows a
      broad hump between 380 and 650 nm, assigned to the electron transition from the
      4f energy level to different 5d sub levels of the Ce(3+) ions at different Y(3+)
      sites. The color of the Y4Si2O7N2:Ce(3+) phosphor can shift from blue to green by
      introducing Tb(3+). In addition, the energy transfer process from Ce(3+) to
      Tb(3+) in the Y4Si2O7N2 host was investigated and discussed in terms of both the
      luminescence spectra and decay curves. The energy transfer critical distance has
      been calculated and evaluated by the concentration quenching method. Therefore,
      the Ce(3+) and Ce(3+)/Tb(3+)-activated Y4Si2O7N2 phosphors can serve as key
      materials for phosphor-converted white-light UV-LEDs. 

PMID- 23868106
TI  - Defining disease beyond conceptual analysis: an analysis of conceptual analysis
      in philosophy of medicine.
AB  - Conceptual analysis of health and disease is portrayed as consisting in the
      confrontation of a set of criteria--a "definition"--with a set of cases, called
      instances of either "health" or "disease." Apart from logical counter-arguments,
      there is no other way to refute an opponent's definition than by providing
      counter-cases. As resorting to intensional stipulation (stipulation of meaning)
      is not forbidden, several contenders can therefore be deemed to have succeeded.
      This implies that conceptual analysis alone is not likely to decide between
      naturalism and normativism. An alternative to this approach would be to examine
      whether the concept of disease can be naturalized.

PMID- 23868105
TI  - Association of response endpoints with survival outcomes in multiple myeloma.
AB  - Since the introduction of the proteasome inhibitor bortezomib and the
      immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with
      multiple myeloma are achieving deep, durable responses and disease control, and
      are living longer. These improvements have afforded more robust analyses of the
      relationship between response and survival. Generally, these studies have
      demonstrated that improvements in the quality of response across all stages of
      treatment are associated with better disease control and longer survival. Thus,
      achievement of maximal response should be strongly considered, particularly in
      the frontline setting, but must also be balanced with tolerability, quality of
      life and patient preferences. In select patients, achievement of a lesser
      response may be adequate to prolong survival, and attempts to treat these
      patients to a deeper response may place them at unnecessary risk without
      significant benefit. Maintenance therapy has been shown to improve the quality of
      response and disease control and, in some studies, survival. Studies support
      maintenance therapy for high-risk patients as a standard of care, and there are
      emerging data supporting maintenance therapy in standard-risk patients to improve
      progression-free and possibly overall survival. Multidrug regimens combining a
      proteasome inhibitor and an IMiD have shown exceptional response outcomes with
      acceptable increases in toxicity in both the frontline and salvage settings, and
      are becoming a standard treatment approach. Moving forward, the use of
      immunophenotypic and molecular response criteria will be essential in better
      understanding the impact of highly active and continuous treatment regimens
      across myeloma patient populations. Future translational studies will help to
      develop antimyeloma agents to their fullest potential. The introduction of novel
      targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors
      carfilzomib and ixazomib (MLN9708), will provide greater options to individualize
      treatment and help patients achieve a clinically meaningful response. 

PMID- 23868108
TI  - Long-term remission of atypical HUS with anti-factor H antibodies after
      cyclophosphamide pulses.
AB  - BACKGROUND: Anti-complement factor H (CFH) autoantibody (Ab)-associated atypical
      hemolytic uremic syndrome (aHUS) has a poor prognosis, but no consensus exists on
      its treatment. METHODS: We report the follow-up of four children with anti-CFH Ab
      (8,000 to >32,000 arbitrary units)-associated aHUS after plasma exchanges (PEs),
      prednisone, and cyclophosphamide pulse therapy with the evolution of anti-CFH Ab
      titers and kidney function. RESULTS: Patient 1 received PEs + prednisone +
      cyclophosphamide pulses after two relapses following PEs and then PEs +
      rituximab. The other three patients were treated with PEs + prednisone +
      cyclophosphamide pulses as a first-line therapy. In our four patients, the
      induction protocol combining PEs + prednisone + cyclophosphamide pulses led to a
      rapid and sustained remission up to 6 years, 4 years and 4 months without any
      maintenance therapy. Kidney function was normal and anti-CFH Ab titer decreased,
      but remained detectable during remission without any clinical or biological signs
      of relapse. CONCLUSIONS: We demonstrate the long-term efficiency and safety of
      cyclophosphamide pulses combined with PEs and prednisone in anti-CFH Ab
      associated aHUS leading to a prolonged decrease in anti-CFH Ab titers and
      prevention of relapses without the need for maintenance therapy.

PMID- 23868107
TI  - Strategies for the preservation of residual renal function in pediatric dialysis
      patients.
AB  - In adults with end-stage renal disease (ESRD), the preservation of residual renal
      function (RRF) has been shown to be associated with decreased mortality and
      improved control of complications of chronic kidney disease. However, less is
      known on the benefits of RRF in the pediatric dialysis population. The purpose of
      this article is to review the clinical significance of RRF and to discuss
      strategies for the preservation of RRF in children with ESRD. 

PMID- 23868109
TI  - Influence of seasonal variation on blood pressure measurements in children,
      adolescents and young adults.
AB  - BACKGROUND: Seasonal fluctuations in outdoor temperature have been shown to
      affect blood pressure in adults. The aim of our study was to determine whether
      blood pressure measurements in children and adolescents in Central Europe undergo
      seasonal variation or are influenced by outdoor temperature. METHODS: The blood
      pressure of 6,714 subjects (3,497 boys, 3,237 girls) aged 3 to 21 (median age
      10.6) years was routinely measured. The study cohort comprised both healthy and
      sick children and adolescents visiting outpatient clinics and during
      hospitalisation. RESULTS: Cross-sectional analysis showed a significant seasonal
      variation in blood pressure measurements. The mean increase of systolic/diastolic
      blood pressure was 4.45/2.42 mmHg during the winter. A significant correlation
      between average outdoor temperature and systolic blood pressure was found (rho = 
      0.074 p < 0.001). However, the effect was only detectable at an average
      temperature below 0  degrees C/32  degrees F and above 10  degrees C/50  degrees
      F. For each 1  degrees C increase in average outdoor temperature, the systolic
      blood pressure fell by 0.12 mmHg. CONCLUSIONS: Blood pressure measurements in
      children and adolescents, even in a temperate climate, are influenced by
      temperature and subject to seasonal variation. Considering seasonal variations in
      blood pressure could be of clinical interest.

PMID- 23868110
TI  - Oestrogens and overactive bladder.
AB  - Estrogens are known to have a major role in the function of the lower urinary
      tract although the role of exogenous estrogen replacement therapy in the
      management of women with lower urinary tract dysfunction remains controversial.
      Whilst for many years systemic and vaginal estrogen therapy was felt to be
      beneficial in the treatment of lower urinary and genital tract symptoms this
      evidence has recently been challenged by large epidemiological studies
      investigating the use of systemic hormone replacement therapy. Consequently the
      role of estrogen in the management of postmenopausal women with Overactive
      Bladder (OAB) remains uncertain. In addition the evidence base regarding the use
      of exogenous estrogen therapy has changed significantly over the last decade and
      has led to a major changes in current clinical practice. The aim of this article
      is to review the evidence for the role of estrogen therapy in the management of
      OAB focusing on current knowledge with regard to both systemic and local estrogen
      therapy as well as investigating the emerging role of combination therapy with
      antimuscarinic agents.

PMID- 23868111
TI  - An audience with : Lee M. Ellis. Interviewd by Man Tsuey Tse.

PMID- 23868112
TI  - Mood disorders: room for improvement.

PMID- 23868114
TI  - Metabolic disease: potassium channel blocker prevents obesity.

PMID- 23868115
TI  - Influenza: viral vector delivers protective antibodies.

PMID- 23868113
TI  - Validating therapeutic targets through human genetics.
AB  - More than 90% of the compounds that enter clinical trials fail to demonstrate
      sufficient safety and efficacy to gain regulatory approval. Most of this failure
      is due to the limited predictive value of preclinical models of disease, and our
      continued ignorance regarding the consequences of perturbing specific targets
      over long periods of time in humans. 'Experiments of nature' - naturally
      occurring mutations in humans that affect the activity of a particular protein
      target or targets - can be used to estimate the probable efficacy and toxicity of
      a drug targeting such proteins, as well as to establish causal rather than
      reactive relationships between targets and outcomes. Here, we describe the
      concept of dose-response curves derived from experiments of nature, with an
      emphasis on human genetics as a valuable tool to prioritize molecular targets in
      drug development. We discuss empirical examples of drug-gene pairs that support
      the role of human genetics in testing therapeutic hypotheses at the stage of
      target validation, provide objective criteria to prioritize genetic findings for
      future drug discovery efforts and highlight the limitations of a target
      validation approach that is anchored in human genetics. 

PMID- 23868116
TI  - Squealing rate indicates dominance rank in the male ring-tailed lemur (Lemur
      catta).
AB  - Squeals are sharp and forceful short-range vocalizations used as aggressive and
      submissive agonistic signals by many mammalian species. The ring-tailed lemur
      (Lemur catta), a female-dominant strepsirhine primate, has a male-specific squeal
      call with proposed male-male agonistic functions and male-female courtship
      functions that have never been empirically tested. The goal of my study is to
      clarify why ring-tailed lemur males squeal at other males and females by applying
      the handicap hypothesis to this male-specific vocalization. This hypothesis has
      rarely been tested in primates, and this study elucidates how the rate of a male
      specific call relates to male-male and male-female behavior in a Malagasy
      strepsirhine. To test whether males squeal towards other males to assert
      dominance, I predict that male squealing rate is positively correlated with
      dominance rank. I further predict that male ring-tailed lemurs squeal at other
      males while engaged in agonistic interactions, and that squealing during an
      interaction is positively correlated with winning that encounter. To test whether
      males squeal towards females as a mate attraction signal, I predict that male
      squealing rate is higher on estrus days, and that estrous females indicate
      attraction by approaching squealing males. From March to July 2010, 480 hr of
      focal data were collected on 25 males aged three and older at Beza Mahafaly
      Special Reserve, Madagascar. I continuously observed each male for 30 min at a
      time and recorded all agonistic interactions and squeal vocalizations using 1-0
      sampling at 2.5-min intervals. Squealing rate was higher during times of male
      male agonism when compared to times without male-male agonism, and males with
      higher dominance ranks had higher squealing rates. In contrast, the mate
      attraction hypothesis was not supported. My results suggest that the male squeal
      is an agonistic signal when used in male-male interaction in ring-tailed lemurs,
      but does not specifically indicate aggression or submission.

PMID- 23868117
TI  - Implantable electrolyte conductance-based pressure sensing catheter, II. Device
      construction and testing.
AB  - Direct measurements of arterial blood pressure most commonly use bulky external
      instrumentation containing a pressure transducer connected to an ex vivo fluid
      filled arterial line, which is subject to several sensing artifacts. In situ
      blood pressure sensors, typically solid state piezoresistive, capacitive, and
      interferometric sensors, are unaffected by these artifacts, but can be expensive
      to produce and miniaturize. We have developed an alternative approach to blood
      pressure measurement based on deformation of an elastic tube filled with
      electrolyte solution. Simple measurement of the electrical conductance of this
      solution as the tube dimensions change allows determination of the external
      pressure. The sensor is made from inexpensive materials and its miniaturization
      is straightforward. In vitro static testing of initial sensor prototypes mounted
      on a catheter tip showed a linear response with applied pressure and a resolution
      of 1 mmHg. In vivo sensing followed catheterization of the sensor into the
      femoral artery of a porcine model through a 7F catheter port. The sensor
      performed comparably to a commercial pressure transducer also connected to the
      catheter port. Due to its scalability and cost, this sensor has the potential for
      use in a range of pressure sensing applications, such as measurement of
      intracranial, spinal, or interstitial pressures. 

PMID- 23868118
TI  - A polymeric cell stretching device for real-time imaging with optical microscopy.
AB  - This paper reports the design, fabrication and characterization of a cell
      stretching device based on the side stretching approach. Numerical simulation
      using finite element method provides a guideline for optimizing the geometry and
      maximizing the output strain of the stretched membrane. An unique PDMS-based
      micro fabrication process was developed for obtaining high parallelization, well
      controlled membrane thickness and an ultra-thin bottom layer that is crucial for
      the use with confocal microscopes. The stretching experiments are fully automated
      with both device actuation and image acquisition. A programmable pneumatic
      control system was built for simultaneous driving of 24 stretching arrays. The
      actuation signals are synchronized with the image acquisition system to obtain
      time-lapse recording of cells grown on the stretched membrane. Experimental
      results verified the characteristics predicted by the simulation. A platform with
      15 stretching units was integrated on a standard 24 mm * 50 mm glass slide. Each
      unit can achieve a maximum strain of more than 60 %. The platform was tested for
      cell growth under cyclic stretching. The preliminary results show that the device
      is compatible with all standard microscopes. 

PMID- 23868119
TI  - Complete nucleotide sequence of porcine circovirus 2 isolated from piglets in
      china.
AB  - A new strain of canine distemper virus, strain HX, has been isolated from piglets
      in China, and its complete genome has been sequenced and analyzed. Phylogenetic
      analysis suggests that HX belongs to the 2d genotype cluster and it is highly
      prevalent in China. 

PMID- 23868120
TI  - Draft Genome Sequence of Agarivorans albus Strain MKT 106T, an Agarolytic Marine
      Bacterium.
AB  - Agarivorans albus is a Gram-negative, strictly aerobic, and agar-hydrolyzing
      marine bacterium. We present the draft genome sequence of the A. albus strain MKT
      106(T), which is composed of 67 contigs (>500 bp) totaling 4,734,285 bp and
      containing 4,397 coding DNA sequences (CDSs), four rRNAs, and 64 tRNA sequences. 

PMID- 23868121
TI  - Complete Genome Sequence of a Novel Reassortant Avian Influenza H1N2 Virus
      Isolated from a Domestic Sparrow in 2012.
AB  - We report here the complete genome sequence of a novel H1N2 avian influenza virus
      strain, A/Sparrow /Guangxi/GXs-1/2012 (H1N2), isolated from a sparrow in the
      Guangxi Province of southern China in 2012. All of the 8 gene segments
      (hemagglutinin [HA], nucleoprotein [NP], matrix [M], polymerase basic 2 [PB2],
      neuraminidase [NA], polymerase acidic [PA], polymerase basic 1 [PB1], and
      nonstructural [NS] genes) of this natural recombinant virus are attributed to the
      Eurasian lineage, and phylogenetic analysis showed that those genes are derived
      from H1N2, H3N1, H3N2, H4N6, H6N2, H10N8, H5N1, and H4N6 avian influenza viruses
      (AIVs). The amino acid motif of the cleavage site of HA is PSIQSR?GLF. The
      sequence analysis will help in understanding the molecular characteristics and
      epidemiology of the H1N2 influenza virus in sparrows. 

PMID- 23868122
TI  - Louping ill virus genome sequence derived from the spinal cord of an infected
      lamb.
AB  - Louping ill virus (LIV) is a zoonotic virus causing fatal encephalitis in young
      sheep and grouse. We have recovered the complete genome sequence from a spinal
      cord sample prepared from a lamb that was naturally infected with LIV. This is
      only the second LIV genome sequence reported and the first prepared from a
      clinical sample. 

PMID- 23868123
TI  - Full Genome Sequence of a Natural Reassortant H9N2 Avian Influenza Virus Isolated
      from Domestic Ducks in Jiangsu Province, China.
AB  - In this study, the complete genomic sequence of a novel reassortant H9N2 avian
      influenza virus (AIV) from domestic ducks in eastern China was reported.
      Phylogenetic analysis showed that seven of the eight genes were all highly
      homologous to the chicken-origin H9N2 viruses, whereas the PB2 gene was
      homologous to the human-origin H1N1 virus, which suggested that domestic ducks
      might play a key role in the genetic reassortment and evolution of H9N2 AIVs in
      eastern China. 

PMID- 23868124
TI  - Complete Genome Sequence of Avian Influenza Virus
      A/chicken/Jiangsu/1001/2013(H5N2), Demonstrating Continuous Reassortance of H5N2
      in China.
AB  - Avian influenza virus A/chicken/Jiangsu/1001/2013(H5N2) was identified from a
      healthy chicken in an eastern China poultry market. Whole-genome analysis
      demonstrated that the H5N2 virus originated from a reassortance between a
      previous A/chicken/Hebei/1102/2010(H5N2) virus and an endemic H5N1 virus. The
      results indicated that continuing reassortance of H5N2 has been occurring in
      domestic poultry of China. 

PMID- 23868125
TI  - Draft Genome Sequence of the Hydrogen- and Ethanol-Producing Anaerobic
      Alkalithermophilic Bacterium Caloramator celer.
AB  - Caloramator celer strain JW/YL-NZ35 is a Gram-positive thermophilic,
      alkalitolerant, and strictly anaerobic bacterium capable of producing hydrogen
      and ethanol under extreme conditions. The draft genome sequence presented here
      will provide valuable information to further explore the physiology of this
      species and its potential for biofuel production. 

PMID- 23868126
TI  - Genome Sequences of Multidrug-Resistant Acinetobacter baumannii Strains from
      Nosocomial Outbreaks in Japan.
AB  - Acinetobacter baumannii has emerged worldwide as an important nosocomial pathogen
      in medical institutions. Here, we present the draft genome sequences of A.
      baumannii strains MRY09-0642, MRY10-0558, and MRY12-0277 that were isolated from
      nosocomial outbreaks in Japan between 2008 and 2012 and that are resistant to
      antimicrobial agents, including carbapenems, fluoroquinolones, and
      aminoglycosides. 

PMID- 23868127
TI  - Genome Sequence of Streptomyces violaceusniger Strain SPC6, a Halotolerant
      Streptomycete That Exhibits Rapid Growth and Development.
AB  - Streptomyces violaceusniger strain SPC6 is a halotolerant streptomycete isolated
      from the Linze desert in China. The strain has a very high growth rate and a
      short life cycle for a streptomycete. For surface-grown cultures, the period from
      spore germination to formation of colonies with mature spore chains is only 2
      days at 37 degrees C. Additionally, the strain is remarkably resistant to
      osmotic, heat, and UV stress compared with other streptomycetes. Analysis of the
      draft genome sequence indicates that the strain has the smallest reported genome
      (6.4 Mb) of any streptomycete. The availability of this genome sequence allows us
      to investigate the genetic basis of adaptation for growth in an extremely arid
      environment. 

PMID- 23868128
TI  - Complete Genome Sequence of a Pseudomonas putida Clinical Isolate, Strain H8234.
AB  - We report the complete genome sequence of Pseudomonas putida strain H8234, which
      was isolated from a hospital patient presenting with bacteremia. This strain has
      a single chromosome (6,870,827 bp) that contains 6,305 open reading frames. The
      strain is not a pathogen but exhibits multidrug resistance associated with 40
      genomic islands. 

PMID- 23868129
TI  - Draft Genome Sequence of the Moderately Halophilic Gammaproteobacterium Halomonas
      anticariensis FP35T.
AB  - Halomonas anticariensis strain FP35(T) is a moderately halophilic bacterium
      isolated from a soil sample taken from Fuente de Piedra, a saline wetland in the
      province of Malaga (Spain), which produces an exopolysaccharide and quorum
      sensing signaling molecules of the type N-acylhomoserine lactone. We report here
      the draft genome sequence of this gammaproteobacterium. 

PMID- 23868130
TI  - Complete Genome Sequence of Salinarchaeum sp. Strain HArcht-Bsk1T, Isolated from
      Hypersaline Lake Baskunchak, Russia.
AB  - The complete genome sequence of a novel halophilic archaeon, Salinarchaeum sp.
      strain HArcht-Bsk1(T), was determined using next-generation sequencing. The
      genome comprises a 3,255,260-bp circular chromosome with a G+C content of 66.7%.
      Automatic annotation of the genome revealed a single rRNA operon, 45 tRNAs, and
      3,013 protein-coding gene sequences. 

PMID- 23868131
TI  - Draft Genome Sequences of Two Yersinia pseudotuberculosis ST43 (O:1b) Strains, B
      7194 and B-7195.
AB  - We report the first draft genome sequences of two Yersinia pseudotuberculosis
      sequence type 43 (ST43) (O:1b) strains, B-7194 and B-7195, isolated in Russia.
      The total lengths of the assemblies are 4,427,121 bp and 4,608,472 bp, and 3,819
      and 4,018 coding sequences, respectively, were predicted within the genomes. 

PMID- 23868132
TI  - Draft Genome Sequence of Indibacter alkaliphilus Strain LW1T, Isolated from Lonar
      Lake, a Haloalkaline Lake in the Buldana District of Maharashtra, India.
AB  - We report the 5.0-Mb genome sequence of Indibacter alkaliphilus strain LW1(T),
      isolated from a haloalkaline crater lake in the Buldana district, Maharashtra,
      India. 

PMID- 23868133
TI  - Draft Genome Sequence of Enterococcus faecium Strain CRL 1879, Isolated from a
      Northwestern Argentinian Artisanal Cheese.
AB  - We report the draft genome sequence of the bacteriocin producer Enterococcus
      faecium strain CRL 1879, isolated from a northwestern Argentinian artisanal
      cheese. The draft genome sequence is composed of 73 contigs for 2,886,747 bp,
      with 3,140 protein-coding genes. Six biosynthetic clusters for bacteriocin class
      II production were found. Typical virulence determinants, which have relevance in
      food safety, were not present. 

PMID- 23868134
TI  - Genome Sequences of Two Pathogenic Streptococcus agalactiae Isolates from the One
      Humped Camel Camelus dromedarius.
AB  - Streptococcus agalactiae causes a range of clinical syndromes in camels (Camelus
      dromedarius). We report the genome sequences of two S. agalactiae isolates that
      induce abscesses in Kenyan camels. These genomes provide novel data on the
      composition of the S. agalactiae "pan genome" and reveal the presence of multiple
      genomic islands. 

PMID- 23868135
TI  - Draft Genome Sequences of Three O157 Enteropathogenic Escherichia coli Isolates.
AB  - We report the draft genome sequences of three enteropathogenic Escherichia coli
      (EPEC) isolates that display the O157 serogroup but do not have the Shiga toxin
      genes (stx), which are characteristic of O157 enterohemorrhagic E. coli (EHEC).
      E. coli strain RN587/1 has the O157:H8 serotype and possesses the EAF plasmid
      characteristic of typical EPEC (J. B. Kaper, J. P. Nataro, and H. L. Mobley, Nat.
      Rev. Microbiol. 2:123-140, 2004). The other two isolates, strains C844-97 and
      C639-08, are both O157:H45 and possess the locus of enterocyte effacement (LEE)
      pathogenicity island; however, they do not contain the EAF plasmid or the stx
      carrying phage. 

PMID- 23868136
TI  - Complete genome sequence of a human enterovirus 71 strain isolated in brunei in
      2006.
AB  - The complete genome sequence of a human enterovirus 71 strain isolated in Brunei
      in 2006 was determined. Phylogenetic analysis based on the complete genome
      sequence classified this strain into subgenogroup B5. 

PMID- 23868137
TI  - Socioeconomic disparity in use of eye care services among US adults with age
      related eye diseases: National Health Interview Survey, 2002 and 2008.
AB  - IMPORTANCE: Individuals with age-related eye disease (ARED) need to use eye care
      services for detection, assessment, and care at regular intervals. OBJECTIVE: To
      explore the association between socioeconomic position (SEP) and use of eye care
      services among US adults with self-reported ARED during 2002 and 2008. DESIGN:
      Data were from the National Health Interview Survey 2002 and 2008. We used
      multiple logistic regression to estimate predictive margins, controlling for
      other factors, and we used the slope index of inequality to measure the
      relationship between SEP and use of eye care services across the entire
      distributions of poverty-income ratio (PIR) and educational attainment. SETTING:
      A cross-sectional, nationally representative sample of adults, with prevalence
      estimates weighted to represent the civilian, noninstitutionalized US population.
      PARTICIPANTS: The sample included US participants in the 2002 (n = 3586) and the
      2008 (n = 3104) National Health Interview Survey who were at least 40 years old
      and reported any ARED (age-related macular degeneration, cataract, diabetic
      retinopathy, or glaucoma). MAIN OUTCOMES AND MEASURES: Use of eye care services;
      SEP was measured by the PIR and educational attainment. RESULTS: In 2002, persons
      with ARED and a PIR of less than 1.50 were significantly less likely than those
      with a PIR of at least 5 to report visiting an eye care provider (62.7% vs 80.1%;
      P < .001) or undergoing a dilated eye examination in the past 12 months (64.3% vs
      80.4%; P < .001), after adjustment for other factors. Similarly, persons with
      less than a high school education were less likely than those with at least a
      college education to report a visit to an eye care provider (62.9% vs 80.8%; P <
      .001) or dilated eye examination (64.8% vs 81.4%; P < .001). In 2002, the slope
      index of inequality showed statistically significant differences for eye care
      provider visits across the levels of education (24.4; P = .006), and in 2008, it
      showed a significant difference for eye care provider visits across the levels of
      educational attainment (25.2; P = .049) and PIR (21.8; P = .01). CONCLUSIONS AND
      RELEVANCE: Significant differences in the use of eye care services by SEP persist
      among US adults with eye diseases.

PMID- 23868138
TI  - Clinically isolated syndromes with no further disease activity suggestive of
      multiple sclerosis at the age of population life expectancy.
AB  - The proportion of patients with clinically isolated syndrome (CIS) reported to
      convert to clinically definite multiple sclerosis varied between 30 and 75%. We
      studied the lifetime probability of remaining in the "CIS only" condition. The
      study was based on the longitudinally followed Gothenburg 1950-1964 incidence
      cohort (n = 306). Survival analysis revealed that 17.8% of 236 attack onset
      patients remained "CIS only". Patients with afferent (optic and sensory) symptoms
      had a better prognosis with approximately 30% of these patients remaining "CIS
      only". Patients who had experienced no relapse during the first 25 years remained
      "CIS only" for the subsequent 25 years of follow-up. 

PMID- 23868139
TI  - Racial disparity in short-term outcomes after gastric bypass surgery.
AB  - BACKGROUND: Roux-en-Y gastric bypass procedure is the most frequently performed
      bariatric surgery for the extremely obese in USA. However, the information about
      the effects of racial/ethnic differences, comorbidities, and medication use on
      weight loss outcomes is limited. The objectives of this study were to investigate
      if race/ethnicity, comorbidities, and medication use affect weight loss
      effectiveness after the surgery. METHODS: This is a retrospective observational
      study conducted at one teaching hospital at Houston metropolitan area, TX, USA.
      Patients between 18 and 64 years, with body mass index (BMI) of >= 40 or BMI of
      >= 35 with comorbidities, who had completed medical evaluations/consultations and
      met insurance policy requirements, were included in the study. RESULTS: From a
      total of 40 patients in the study (40 % African Americans, 35 % Caucasians, 17.5
      % Hispanics, 7.5 % others), the weight loss was significantly greater in
      Caucasian patients at 6 months after the surgery, with mean percentage excess
      weight loss (%EWL) of 40.6 +/- 17.3, as compared to all other racial groups
      combined at %EWL of 30.9 +/- 11.5 (p value 0.04). No association was found
      between the 6-month weight loss and other variables including age, gender, BMI
      prior to surgery, comorbidities, and total number of medications taken before the
      surgery. CONCLUSIONS: This study found that Caucasian patients had a
      significantly greater %EWL at 6 months post-op as compared to their African
      American and Hispanic counterparts. No other variables exhibited significant
      impact on the weight loss. Further studies with a larger sample size are needed
      to confirm the results from this study.

PMID- 23868140
TI  - Parameter selection and stimulating effects of an adjustable gastric electrical
      stimulator in dogs.
AB  - BACKGROUND: Gastric electrical stimulation (GES) has been proposed as a promising
      therapeutic option in treating obesity for 20 years. Currently, the available
      device of GES cannot meet the clinical needs. The purpose of this study is to
      verify the effect of a new type of adjustable gastric electrical stimulator in
      reducing food intake and body weight. METHODS: Eight beagle dogs randomly
      followed GES and sham GES for 3 months in a crossover design. Parameters were
      adjusted and individualized during the experiment. Symptoms of GES were recorded,
      and the effective parameters were selected. Resistance to GES was assessed. Food
      intake and body weight were measured to evaluate the effect of GES. RESULTS: The
      effective parameters were varied among the dogs. Resistance to GES was observed
      in different periods in dogs. Parameters needed to be adjusted every 10.2 +/- 2.1
      days during the period of GES. Food intake during GES for 3 months was
      significantly reduced than that during sham GES of 3 months (P < 0.05). With the
      decreased food intake, body weight was significantly reduced by the end of GES of
      3 months compared with that of sham GES of 3 months (P < 0.05). CONCLUSIONS: Food
      intake and body weight of dogs are significantly reduced by adjustable GES.
      Individual parameters and resistance during GES are required to be considered.
      The new adjustable device may have good prospects of clinical application for
      obesity.

PMID- 23868142
TI  - Local temperature redistribution and structural transition during joule-heating
      driven conductance switching in VO2.
AB  - Joule-heating induced conductance-switching is studied in VO2 , a Mott insulator.
      Complementary in situ techniques including optical characterization, blackbody
      microscopy, scanning transmission X-ray microscopy (STXM) and numerical
      simulations are used. Abrupt redistribution in local temperature is shown to
      occur upon conductance-switching along with a structural phase transition, at the
      same current. 

PMID- 23868141
TI  - Significant weight loss and rapid resolution of diabetes and dyslipidemia during
      short-term follow-up after laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Bariatric surgery has been established as the best option of
      treatment for morbid obesity. Recently, laparoscopic sleeve gastrectomy (SG) has
      become very popular because of good postoperative weight loss and low morbidity.
      The aim of this study was to report our single-center experience with SG
      regarding feasibility, morbidity, and outcome. METHODS: From January 2006 to
      December 2011, 93 patients (68 female) with a median age of 46 years underwent
      laparoscopic SG at our department. Thirteen patients had a history of gastric
      banding with insufficient weight loss or band-related complications. Clinical
      outcome and laboratory findings were analyzed. RESULTS: The mean preoperative and
      postoperative body mass index (BMI) was 44.1 +/- 6.9 and 33.4 +/- 6.8 kg/m(2),
      respectively (p < 0.001). The mean excessive body weight loss after a median
      follow-up of 11.9 months was 55.7 % +/- 24.9 %. Three bleedings, two staple line
      leakages, and a deep wound infection required conversion to laparotomy (n = 1),
      reoperation (n = 4), or endoscopic stent implantation (n = 2). Resolution of
      diabetes and dyslipidemia was seen in 85 and 50 % of patients, respectively.
      Blood test results of HbA1c, cholesterols, triglycerides, and leptin showed
      significant postoperative improvement. CONCLUSIONS: Laparoscopic SG represents a
      feasible bariatric procedure with good short-term weight loss, low morbidity
      rate, and efficient resolution of diabetes and dyslipidemia, especially in
      patients with lower BMI. The significant decrease of leptin necessitates further
      studies to understand the ambiguous role of leptin in bariatric surgery.

PMID- 23868143
TI  - Fas/CD95 ligation induces proliferation of primary fetal astrocytes through a
      mechanism involving caspase 8-mediated ERK activation.
AB  - BACKGROUND: Fas/CD95 is the best-studied member of the death receptor (DR)
      superfamily in the central nervous system where it can trigger cellular responses
      other than apoptosis, including the promotion of neurogenesis and neuritogenesis,
      stimulation of the progression of gliomas, and regulation of the immune response
      of astrocytes. METHODS: We have investigated the role of Fas/CD95 in the
      regulation of the proliferation of fetal astrocytes in vitro, as well as the
      signalling pathways involved. RESULTS: Fas/CD95 ligation stimulated the
      proliferation of primary fetal astrocytes, through a mechanism that depends on
      the activation of caspase 8 and subsequent phosphorylation of extracellular
      signal regulated kinase (ERK). Interestingly this proliferative effect is only
      observed with a low dose of the Fas/CD95 agonist. In contrast, when primary
      astrocytes are challenged with a high dose of the Fas/CD95 agonist significant
      cell death occurs. CONCLUSIONS: Our findings support that, besides its effects on
      cell survival, Fas/CD95 may play a complex and prominent role in the regulation
      of astrocyte proliferation during development.

PMID- 23868144
TI  - Can we use circulating biomarkers to monitor bone turnover in CKD haemodialysis
      patients? Hypotheses and facts.
AB  - Assessing bone turnover is a key diagnostic tool in the global management of
      chronic kidney disease-mineral and bone disorder (CKD-MBD). Since bone biopsy is
      invasive and cannot be repeated in clinical practice and because bone
      histomorphometry is less available due to the lack of specialized laboratories,
      we will focus on potential biomarkers used to assess and monitor bone turnover.
      After briefly reviewing the pathophysiology of bone turnover in CKD and
      haemodialysis patients, we will focus on the strengths and limitations of the now
      recommended biomarkers, i.e. parathormone and bone-specific alkaline phosphatase.
      We will consider the clinical and also the biological aspects of the topic and
      also insist on the use of these biomarkers for the monitoring, and the follow-up
      of the turnover in haemodialysis subjects. Finally, we will discuss some of the
      most promising, but still not recommended, emerging biomarkers. 

PMID- 23868145
TI  - Obesity-related glomerulopathy and the nephron complement.
AB  - Obesity-related glomerulopathy (ORG) is a secondary form of glomerular disease
      that can occur in individuals with obesity. However, the absolute risk for an
      obese individual to develop progressive renal deterioration is low. Therefore,
      obesity alone appears to be insufficient to develop such severe renal injury, and
      there are likely other factors that contribute to the development of this entity.
      The glomerular hyperfiltration found in patients with ORG has been postulated to
      lead to structural abnormalities in glomeruli, such as glomerulomegaly and focal
      segmental glomerular sclerosis, in a manner analogous to that described in
      patients with reduced renal mass. In fact, recent studies suggest that a
      reduction in nephron mass is implicated in patients with ORG and synergistically
      contributes to the development of this renal complication together with obesity
      induced changes in renal hemodynamics. 

PMID- 23868146
TI  - Plasmon-induced oxidation of gold nanoparticles on TiO2 in the presence of
      ligands.
AB  - The mechanism of plasmon-induced charge separation of gold nanoparticles (Au NPs)
      on TiO2 was investigated with the help of anionic ligands. Au NPs are oxidized in
      the presence of KX (X = SCN, Br or Cl), chiefly via direct oxidation to [AuX4](
      ). The reactivity of Au NPs depends on the solution pH, the type of anion ligands
      and the excitation wavelength, suggesting that the photopotential of Au NPs
      during plasmon-induced charge separation depends on both the flatband potential
      of TiO2 and the energy of irradiated photons. The results indicate that the
      reactivity and efficiency of the plasmon-induced charge separation and
      accompanying reactions can be tuned and optimized by changing those factors. 

PMID- 23868148
TI  - Abnormal functional network connectivity among resting-state networks in children
      with frontal lobe epilepsy.
AB  - BACKGROUND AND PURPOSE: Epilepsy is considered a disorder of neural networks. The
      aims of this study were to assess functional connectivity within resting-state
      networks and functional network connectivity across resting-state networks by use
      of resting-state fMRI in children with frontal lobe epilepsy and to relate
      changes in resting-state networks with neuropsychological function. MATERIALS AND
      METHODS: Fifteen patients with frontal lobe epilepsy and normal MR imaging and 14
      healthy control subjects were recruited. Spatial independent component analysis
      was used to identify the resting-state networks, including frontal, attention,
      default mode network, sensorimotor, visual, and auditory networks. The Z-maps of
      resting-state networks were compared between patients and control subjects. The
      relation between abnormal connectivity and neuropsychological function was
      assessed. Correlations from all pair-wise combinations of independent components
      were performed for each group and compared between groups. RESULTS: The frontal
      network was the only network that showed reduced connectivity in patients
      relative to control subjects. The remaining 5 networks demonstrated both reduced
      and increased functional connectivity within resting-state networks in patients.
      There was a weak association between connectivity in frontal network and
      executive function (P = .029) and a significant association between sensorimotor
      network and fine motor function (P = .004). Control subjects had 79 pair-wise
      independent components that showed significant temporal coherence across all
      resting-state networks except for default mode network-auditory network. Patients
      had 66 pairs of independent components that showed significant temporal coherence
      across all resting-state networks. Group comparison showed reduced functional
      network connectivity between default mode network-attention, frontal
      sensorimotor, and frontal-visual networks and increased functional network
      connectivity between frontal-attention, default mode network-sensorimotor, and
      frontal-visual networks in patients relative to control subjects. CONCLUSIONS: We
      found abnormal functional connectivity within and across resting-state networks
      in children with frontal lobe epilepsy. Impairment in functional connectivity was
      associated with impaired neuropsychological function.

PMID- 23868147
TI  - Accuracy of vessel-encoded pseudocontinuous arterial spin-labeling in
      identification of feeding arteries in patients with intracranial arteriovenous
      malformations.
AB  - BACKGROUND AND PURPOSE: Identifying feeding arteries of intracranial AVMs is very
      important for preoperative evaluation. DSA remains the reference standard for
      diagnosis but is invasive. Our aim was to evaluate the diagnostic accuracy of
      vessel-encoded pseudocontinuous arterial spin-labeling in identifying feeding
      arteries of intracranial AVMs by using DSA as the criterion standard. MATERIALS
      AND METHODS: Eighteen patients with AVMs were examined with vessel-encoded
      pseudocontinuous arterial spin-labeling and DSA. Three postlabeling delays
      (postlabeling delay = 1, 1.3, and 1.6 seconds) were applied in 6 patients, and a
      single postlabeling delay (1 second) was applied in the remainder. Perfusion
      weighted images were decoded into individual vascular territories with standard
      and relative tagging efficiencies, respectively. The supply fraction of each
      feeding artery to the AVM was calculated. The within-subject ANOVA was applied to
      compare supply fractions acquired across 3 postlabeling delays. Receiver
      operating characteristic analysis curves were calculated to evaluate the
      diagnostic accuracy of vessel-encoded pseudocontinuous arterial spin-labeling for
      identifying the feeding arteries of AVMs. RESULTS: There were no significant
      differences in supply fractions of the 3 major arteries to AVMs acquired with 3
      postlabeling delays (P > .05). For vessel-encoded pseudocontinuous arterial spin
      labeling with standard labeling efficiencies, the area under the receiver
      operating characteristic analysis curve was 0.942. The optimal cutoff of the
      supply fraction for identifying feeding arteries was 15.17%, and the resulting
      sensitivity and specificity were 84.62% and 93.33%, respectively. For vessel
      encoded pseudocontinuous arterial spin-labeling with relative labeling
      efficiencies, the area under the receiver operating characteristic analysis curve
      was 0.957. The optimal cutoff of the supply fraction was 11.73%, which yielded an
      89.74% sensitivity and 93.33% specificity. CONCLUSIONS: The contribution fraction
      of each feeding artery of the AVM can be reliably estimated by using vessel
      encoded pseudocontinuous arterial spin-labeling. Vessel-encoded pseudocontinuous
      arterial spin-labeling with either standard or relative labeling efficiencies
      offers a high level of diagnostic accuracy compared with DSA for identifying
      feeding arteries.

PMID- 23868149
TI  - No evidence for impairment of venous hemodynamics in children or young adults
      with pediatric-onset multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Chronic cerebrospinal venous insufficiency is a
      postulated etiologic factor for multiple sclerosis, but the higher frequency with
      longer disease duration and progressive disability suggests that chronic
      cerebrospinal venous insufficiency is secondary to chronic disease. We evaluated
      the presence of chronic cerebrospinal venous insufficiency in pediatric-onset MS.
      MATERIALS AND METHODS: Twenty-six pediatric patients with MS (18 years of age or
      younger), 26 age-matched healthy controls, and 13 young adults with pediatric
      onset MS underwent sonography of the internal jugular, vertebral, and deep
      cerebral veins. Five venous hemodynamic criteria were assessed, with 2 criteria
      required for chronic cerebrospinal venous insufficiency. MR imaging studies,
      performed in the pediatric patients with MS and healthy control groups, included
      intracranial 2D time-of-flight MR venography and velocity-sensitive phase
      contrast sequences. Contrast-enhanced brain MR images were obtained in pediatric
      patients with MS to further evaluate venous patency. We used paired t tests,
      Wilcoxon matched pairs, McNemar tests, and exact conditional logistic regression
      to estimate the association of chronic cerebrospinal venous insufficiency with
      MS. RESULTS: Fifty participants (73.5%) had normal ultrasound findings, 15
      (23.1%) met 1 venous hemodynamic criterion, and 2 pediatric patients with MS and
      1 young adult with pediatric-onset MS met chronic cerebrospinal venous
      insufficiency criteria. Chronic cerebrospinal venous insufficiency was not
      associated with MS (odds ratio, 2.41; 95% CI, 0.19-infinity). Demographic and
      disease characteristics did not differ between the patients with MS meeting
      chronic cerebrospinal venous insufficiency criteria (n = 3) and those who did not
      (n = 36; all, P > .05). The mean (SD) MR imaging measures of intracerebral flow
      did not differ between the 2 pediatric patients with MS meeting chronic
      cerebrospinal venous insufficiency criteria (0.85 +/- 0.11) and healthy controls
      (0.87 +/- 0.16, P = .50); no child demonstrated venous obstruction. CONCLUSIONS:
      Chronic cerebrospinal venous insufficiency is rarely observed in children or
      young adults with pediatric-onset MS. Venous anatomy and flow rates indicate that
      venous outflow is intact in pediatric patients with MS. Our findings argue
      against chronic cerebrospinal venous insufficiency as a component of MS etiology.

PMID- 23868150
TI  - Diffusion-weighted imaging of orbital masses: multi-institutional data support a
      2-ADC threshold model to categorize lesions as benign, malignant, or
      indeterminate.
AB  - BACKGROUND AND PURPOSE: DWI has been increasingly used to characterize orbital
      masses and provides quantitative information in the form of the ADC, but studies
      of DWI of orbital masses have shown a range of reported sensitivities,
      specificities, and optimal threshold ADC values for distinguishing benign from
      malignant lesions. Our goal was to determine the optimal use of DWI for imaging
      orbital masses through aggregation of data from multiple centers. MATERIALS AND
      METHODS: Source data from 3 previous studies of orbital mass DWI were aggregated,
      and additional published data points were gathered. Receiver operating
      characteristic analysis was performed to determine the sensitivity, specificity,
      and optimal ADC thresholds for distinguishing benign from malignant masses.
      RESULTS: There was no single ADC threshold that characterized orbital masses as
      benign or malignant with high sensitivity and specificity. An ADC of less than
      0.93 * 10(-3) mm(2)/s was more than 90% specific for malignancy, and an ADC of
      less than 1.35 * 10(-3) mm(2)/s was more than 90% sensitive for malignancy. With
      these 2 thresholds, 33% of this cohort could be characterized as "likely
      malignant," 29% as "likely benign," and 38% as "indeterminate." CONCLUSIONS: No
      single ADC threshold is highly sensitive and specific for characterizing orbital
      masses as benign or malignant. If we used 2 thresholds to divide these lesions
      into 3 categories, however, a majority of orbital masses can be characterized
      with >90% confidence.

PMID- 23868151
TI  - 3T MRI quantification of hippocampal volume and signal in mesial temporal lobe
      epilepsy improves detection of hippocampal sclerosis.
AB  - BACKGROUND AND PURPOSE: In mesial temporal lobe epilepsy, MR imaging
      quantification of hippocampal volume and T2 signal can improve the sensitivity
      for detecting hippocampal sclerosis. However, the current contributions of these
      analyses for the diagnosis of hippocampal sclerosis in 3T MRI are not clear. Our
      aim was to compare visual analysis, volumetry, and signal quantification of the
      hippocampus for detecting hippocampal sclerosis in 3T MRI. MATERIALS AND METHODS:
      Two hundred three patients with mesial temporal lobe epilepsy defined by clinical
      and electroencephalogram criteria had 3T MRI visually analyzed by imaging
      epilepsy experts. As a second step, we performed automatic quantification of
      hippocampal volumes with FreeSurfer and T2 relaxometry with an in-house software.
      MRI of 79 healthy controls was used for comparison. RESULTS: Visual analysis
      classified 125 patients (62%) as having signs of hippocampal sclerosis and 78
      (38%) as having normal MRI findings. Automatic volumetry detected atrophy in 119
      (95%) patients with visually detected hippocampal sclerosis and in 10 (13%) with
      visually normal MR imaging findings. Relaxometry analysis detected hyperintense
      T2 signal in 103 (82%) patients with visually detected hippocampal sclerosis and
      in 15 (19%) with visually normal MR imaging findings. Considered together,
      volumetry plus relaxometry detected signs of hippocampal sclerosis in all except
      1 (99%) patient with visually detected hippocampal sclerosis and in 22 (28%) with
      visually normal MR imaging findings. CONCLUSIONS: In 3T MRI visually inspected by
      experts, quantification of hippocampal volume and signal can increase the
      detection of hippocampal sclerosis in 28% of patients with mesial temporal lobe
      epilepsy.

PMID- 23868152
TI  - Evaluation of diffusivity in the anterior lobe of the pituitary gland: 3D turbo
      field echo with diffusion-sensitized driven-equilibrium preparation.
AB  - BACKGROUND AND PURPOSE: 3D turbo field echo with diffusion-sensitized driven
      equilibrium preparation is a non-echo-planar technique for DWI, which enables
      high-resolution DWI without field inhomogeneity-related image distortion. The
      purpose of this study was to evaluate the feasibility of diffusion-sensitized
      driven-equilibrium turbo field echo in evaluating diffusivity in the normal
      pituitary gland. MATERIALS AND METHODS: First, validation of diffusion-sensitized
      driven-equilibrium turbo field echo was attempted by comparing it with echo
      planar DWI. Five healthy volunteers were imaged by using diffusion-sensitized
      driven-equilibrium turbo field echo and echo-planar DWI. The imaging voxel size
      was 1.5 * 1.5 * 1.5 mm(3) for diffusion-sensitized driven-equilibrium turbo field
      echo and 1.5 * 1.9 * 3.0 mm(3) for echo-planar DWI. ADCs measured by the 2
      methods in 15 regions of interests (6 in gray matter and 9 in white matter) were
      compared by using the Pearson correlation coefficient. The ADC in the pituitary
      anterior lobe was then measured in 10 volunteers by using diffusion-sensitized
      driven-equilibrium turbo field echo, and the results were compared with those in
      the pons and vermis by using a paired t test. RESULTS: The ADCs from the 2
      methods showed a strong correlation (r = 0.79; P < .0001), confirming the
      accuracy of the ADC measurement with the diffusion-sensitized driven-equilibrium
      sequence. The ADCs in the normal pituitary gland were 1.37 +/- 0.13 * 10(-3)
      mm(2)/s, which were significantly higher than those in the pons (1.01 +/- 0.24 *
      10(-3) mm(2)/s) and the vermis (0.89 +/- 0.25 * 10(-3) mm(2)/s, P < .01).
      CONCLUSIONS: We demonstrated that diffusion-sensitized driven-equilibrium turbo
      field echo is feasible in assessing ADC in the pituitary gland.

PMID- 23868153
TI  - Vertebral augmentation in patients with multiple myeloma: a pooled analysis of
      published case series.
AB  - BACKGROUND AND PURPOSE: Studies examining the efficacy of vertebroplasty and
      kyphoplasty in patients with vertebral fractures from multiple myeloma are
      limited. We sought to perform a systematic review of published case studies
      examining changes in pain, disability, and analgesic drug use in patients with
      multiple myeloma who have undergone vertebral augmentation. MATERIALS AND
      METHODS: We performed a pooled analysis of published case series of vertebral
      augmentation in patients with multiple myeloma. Twenty-three studies (9
      kyphoplasty, 12 vertebroplasty, and 2 of both) with data on 923 patients were
      identified from a PubMed search. Quantitative outcome data included the Visual
      Analog Scale, the Brief Pain Inventory, the Short Form 36 Health Survey, and the
      Owestry Disability Index. Time periods were consolidated into 3: postoperatively
      <=1 week, 1 week to 1 year, and >=1 year. Change in analgesic use was also
      studied. Data were compared by using nonparametric tests and matched t tests for
      temporally linked data. RESULTS: Patients achieved a decrease in pain across all
      consolidated time periods. Pain, as measured on a 10-point scale, decreased by
      4.8 points up to 1 week, 4.6 points up to 1 year, and 4.4 points after a year (P
      < .001). Decrease in pain was apparent early after treatment and was sustained
      with time. Kyphoplasty and vertebroplasty were equally effective in reducing pain
      scores because differences between procedures for each time period were
      insignificant (P < .9 for <1 week, P < 1.0 for <=1 year, and P < .9 for >1 year.
      CONCLUSIONS: Our analysis demonstrates that vertebral augmentation is effective
      in patients with multiple myeloma.

PMID- 23868154
TI  - Decreased T1 contrast between gray matter and normal-appearing white matter in
      CADASIL.
AB  - BACKGROUND AND PURPOSE: CADASIL is the most frequent hereditary small-vessel
      disease of the brain. The clinical impact of various MR imaging markers has been
      repeatedly studied in this disorder, but alterations of contrast between gray
      matter and normal-appearing white matter remain unknown. The aim of this study
      was to evaluate the contrast alterations between gray matter and normal-appearing
      white matter on T1-weighted images in patients with CADASIL compared with healthy
      subjects. MATERIALS AND METHODS: Contrast between gray matter and normal
      appearing white matter was assessed by using histogram analyses of 3D T1 high
      resolution MR imaging in 23 patients with CADASIL at the initial stage of the
      disease (Mini-Mental State Examination score > 24 and modified Rankin scale score
      <= 1; mean age, 53.5 +/- 11.1 years) and 30 age- and sex-matched controls.
      RESULTS: T1 contrast between gray matter and normal-appearing white matter was
      significantly reduced in patients compared with age- and sex-matched controls
      (patients: 1.35 +/- 0.08 versus controls: 1.43 +/- 0.04, P < 10(-5)). This
      reduction was mainly driven by a signal decrease in normal-appearing white
      matter. Contrast loss was strongly related to the volume of white matter
      hyperintensities. CONCLUSIONS: Conventional 3D T1 imaging shows significant loss
      of contrast between gray matter and normal-appearing white matter in CADASIL.
      This probably reflects tissue changes in normal-appearing white matter outside
      signal abnormalities on T2 or FLAIR sequences. These contrast alterations should
      be taken into account for image interpretation and postprocessing.

PMID- 23868155
TI  - 4D-CT for preoperative localization of abnormal parathyroid glands in patients
      with hyperparathyroidism: accuracy and ability to stratify patients by unilateral
      versus bilateral disease in surgery-naive and re-exploration patients.
AB  - BACKGROUND AND PURPOSE: 4D-CT is an emerging technique that uses high-resolution
      images, multiplanar reformats, and perfusion characteristics to identify abnormal
      parathyroid glands in patients with hyperparathyroidism. This study evaluates the
      accuracy of 4D-CT for localization and lateralization of abnormal parathyroid
      glands in preoperative planning for minimally invasive parathyroidectomy vs
      bilateral neck exploration at a tertiary referral center. MATERIALS AND METHODS:
      Radiology, pathology, and operative reports were retrospectively reviewed for 208
      patients with hyperparathyroidism who underwent 4D-CT and parathyroid surgery
      between May 2008 and January 2012. 4D-CT performance in localizing side and site
      was determined by use of surgical and pathologic findings as a reference.
      RESULTS: Of 208 patients, 155 underwent initial surgery and 53 underwent re
      exploration parathyroid surgery. No lesions were found in 8 patients (3.8%). A
      total of 284 lesions were found in 200 patients; 233 were correctly localized by
      4D-CT (82.0%). Of the 200 patients with parathyroid lesions, 146 underwent
      unilateral and 54 bilateral neck exploration. 4D-CT correctly identified
      unilateral vs bilateral disease in 179 (89.5%) of 200. 4D-CT correctly localized
      parathyroid lesions in 126 of the unilateral cases (86.3%). In the re-exploration
      cohort, 4D-CT correctly identified unilateral vs bilateral disease in 46 (95.8%)
      of 48. There was no statistically significant difference in subgroups stratified
      by surgery type (primary or subsequent) and number of scan phases (3 or 4) (P >
      .56). CONCLUSIONS: 4D-CT leverages modern high-resolution CT scanning and dynamic
      contrast enhancement to localize abnormal parathyroid glands in patients with
      hyperparathyroidism of any cause and can be used for planning minimally invasive
      parathyroidectomy vs bilateral neck exploration.

PMID- 23868157
TI  - CTA for screening of complicated atherosclerotic carotid plaque--American Heart
      Association type VI lesions as defined by MRI.
AB  - BACKGROUND AND PURPOSE: High-resolution carotid MR imaging can accurately
      identify complicated American Heart Association lesion type VI plaques, which are
      characterized by thrombus, hemorrhage, or a ruptured fibrous cap. The purpose of
      this study is to evaluate whether CTA can be used as screening tool to predict
      the presence or absence of American Heart Association lesion type VI plaques as
      defined by high-resolution MR imaging. METHODS: Fifty-one patients with suspected
      ischemic stroke or TIA with carotid CTA and carotid MR imaging performed within
      14 days of the event/admission from April 2008 to December 2010 were reviewed.
      Vessels with stents or occlusion were excluded (n = 2). Each carotid artery was
      assigned an American Heart Association lesion type classification by MR imaging.
      The maximum wall thickness, maximum soft plaque component thickness, maximum
      calcified component thickness, and its attenuation (if the soft plaque component
      thickness was >2 mm) were obtained from the CTA. RESULTS: The maximum soft plaque
      component thickness proved the best discriminating factor to predict a
      complicated plaque by MR imaging, with a receiver operating characteristic area
      under the curve of 0.89. The optimal sensitivity and specificity for detection of
      complicated plaque by MR imaging was achieved with a soft plaque component
      thickness threshold of 4.4 mm (sensitivity, 0.65; specificity, 0.94; positive
      predictive value, 0.75; and negative predictive value, 0.9). No complicated
      plaque had a soft tissue plaque thickness <2.2 mm (negative predictive value, 1)
      and no simple (noncomplicated) plaque had a thickness >5.6 mm (positive
      predictive value, 1). CONCLUSIONS: Maximum soft plaque component thickness as
      measured by carotid CTA is a reliable indicator of a complicated plaque, with a
      threshold of 2.2 mm representing little to no probability of a complicated
      American Heart Association lesion type VI plaque.

PMID- 23868156
TI  - Automated white matter total lesion volume segmentation in diabetes.
AB  - BACKGROUND AND PURPOSE: WM lesion segmentation is often performed with the use of
      subjective rating scales because manual methods are laborious and tedious;
      however, automated methods are now available. We compared the performance of
      total lesion volume grading computed by use of an automated WM lesion
      segmentation algorithm with that of subjective rating scales and expert manual
      segmentation in a cohort of subjects with type 2 diabetes. MATERIALS AND METHODS:
      Structural T1 and FLAIR MR imaging data from 50 subjects with diabetes (age, 67.7
      +/- 7.2 years) and 50 nondiabetic sibling pairs (age, 67.5 +/- 9.4 years) were
      evaluated in an institutional review board-approved study. WM lesion segmentation
      maps and total lesion volume were generated for each subject by means of the
      Statistical Parametric Mapping (SPM8) Lesion Segmentation Toolbox. Subjective WM
      lesion grade was determined by means of a 0-9 rating scale by 2 readers. Ground
      truth total lesion volume was determined by means of manual segmentation by
      experienced readers. Correlation analyses compared manual segmentation total
      lesion volume with automated and subjective evaluation methods. RESULTS:
      Correlation between average lesion segmentation and ground-truth total lesion
      volume was 0.84. Maximum correlation between the Lesion Segmentation Toolbox and
      ground-truth total lesion volume (rho = 0.87) occurred at the segmentation
      threshold of k = 0.25, whereas maximum correlation between subjective lesion
      segmentation and the Lesion Segmentation Toolbox (rho = 0.73) occurred at k =
      0.15. The difference between the 2 correlation estimates with ground-truth was
      not statistically significant. The lower segmentation threshold (0.15 versus
      0.25) suggests that subjective raters overestimate WM lesion burden. CONCLUSIONS:
      We validate the Lesion Segmentation Toolbox for determining total lesion volume
      in diabetes-enriched populations and compare it with a common subjective WM
      lesion rating scale. The Lesion Segmentation Toolbox is a readily available
      substitute for subjective WM lesion scoring in studies of diabetes and other
      populations with changes of leukoaraiosis.

PMID- 23868158
TI  - Comparative effectiveness of ruptured cerebral aneurysm therapies: propensity
      score analysis of clipping versus coiling.
AB  - BACKGROUND AND PURPOSE: The relative merits of treating ruptured aneurysms with
      clipping versus coiling continue to be a topic of debate. We evaluated a
      national, multihospital patient data base to examine recent trends in ruptured
      aneurysm therapies and to compare peri-procedural outcomes between clipping and
      coiling treatments. MATERIALS AND METHODS: The Premier Perspective data base was
      used to identify patients hospitalized between 2006-2011 for ruptured aneurysm
      who underwent clipping or coiling therapy. A propensity score model, representing
      the probability of receiving clipping, was generated for each patient by use of
      relevant patient and hospital variables. After Greedy-type matching of the
      propensity score, the risk of in-hospital mortality and morbidity was compared
      between clipping and coiling cohorts. RESULTS: A total of 5229 patients with
      ruptured aneurysm (1228 clipping, 4001 coiling) treated at 125 hospitals were
      identified. Clipping therapy frequency decreased from 27% in 2006 to 21% in 2011.
      After propensity score adjustment, in-hospital mortality risk was similar between
      groups (OR = 0.94 [95% CI, 0.73-1.21]; P = .62). However, unfavorable outcomes
      were more common after clipping compared with coiling, including discharge to
      long-term care (OR = 1.32 [95% CI, 1.12-1.56]; P = .0006), ischemic complications
      (OR = 1.51 [95% CI, 1.24-1.83]; P = .0009), neurologic complications (OR = 1.64
      [95% CI, 1.18-2.27]; P = .0018), and other surgical complications (OR = 1.55 [95%
      CI, 1.05-2.33]; P = .0240). CONCLUSIONS: This study of a data base of multiple
      hospitals in the United States demonstrates that clipping of ruptured cerebral
      aneurysms resulted in greater adjusted morbidity compared with coiling.

PMID- 23868159
TI  - Differences in the angiographic evaluation of coiled cerebral aneurysms between a
      core laboratory reader and operators: results of the Cerecyte Coil Trial.
AB  - BACKGROUND AND PURPOSE: Independent evaluation of angiographic images is becoming
      widely applied in the assessment of treatment outcomes of cerebral aneurysms. In
      the current study, we assessed the agreement between an independent core
      laboratory and the operators regarding angiographic appearance in a recent
      randomized, controlled trial. MATERIALS AND METHODS: Data were derived from the
      Cerecyte Coil Trial. Angiographic images of each coiled aneurysm, taken
      immediately after embolization and at 5- to 7-month follow-up, were evaluated by
      the operator at the treating center and by an independent neuroradiologist at the
      core laboratory. For the purpose of this study, images were interpreted on a 3
      point scale to provide uniformity for analysis; grade 1: complete occlusion,
      grade 2: neck remnant; and grade 3: sac filling. "Unfavorable angiographic
      appearance" was defined as grade 3 at follow-up or interval worsening of grade
      between the 2 time points. RESULTS: The study included 434 aneurysms. Immediately
      after embolization, grade 3 was reported by operators in 39 (9%) compared with 52
      (12%) by the core laboratory (P = .159). On follow-up, grade 3 was reported by
      operators in 44 (10%) compared with 81 (19%) by the core laboratory (P < .0001).
      Overall, operators noted unfavorable angiographic appearance in 78 (18%) compared
      with 134 (31%) by the core laboratory (P < .0001). At every time point, agreement
      between the core laboratory and the operators was slight. CONCLUSIONS:
      Unfavorable angiographic appearance was noted almost twice as frequently by an
      independent core laboratory as compared with the operators. Planning of trials
      and interpretation of published studies should be done with careful attention to
      the mode of angiographic appearance interpretation.

PMID- 23868160
TI  - Acute stroke imaging research roadmap II and international survey of acute stroke
      imaging capabilities: we need your help!

PMID- 23868161
TI  - Intracranial arteries in individuals with the elastin gene hemideletion of
      Williams syndrome.
AB  - BACKGROUND AND PURPOSE: Williams syndrome, a rare genetic disorder with a
      striking neurobehavioral profile characterized by extreme sociability and
      impaired visuospatial construction abilities, is caused by a hemideletion that
      includes the elastin gene, resulting in frequent supravavular aortic stenosis and
      other stenotic arterial lesions. Strokes have been reported in Williams syndrome.
      Although the extracranial carotid artery has been studied in a sample of patients
      with Williams syndrome, proximal intracranial arteries have not. MATERIALS AND
      METHODS: Using MRA, we studied the intracranial vessels in 27 participants: 14
      patients with Williams syndrome (age range, 18-44 years; mean age, 27.3 +/- 9.1;
      43% women) and 13 healthy control participants with similar age and sex
      distribution (age range, 22-52 years; mean age, 33.4 +/- 7.6; 46% women). All
      participants with Williams syndrome had hemideletions of the elastin gene.
      Blinded to group allocation or to any other clinical data, a neuroradiologist
      determined the presence of intracranial vascular changes in the 2 groups.
      RESULTS: The Williams syndrome group and the healthy control group had similar
      patency of the proximal intracranial arteries, including the internal carotid and
      vertebral arteries; basilar artery; and stem and proximal branches of the
      anterior cerebral artery, MCA, and posterior cerebral arteries. The
      postcommunicating segment of the anterior cerebral artery was longer in the
      Williams syndrome group. CONCLUSIONS: Despite the elastin haploinsufficiency, the
      proximal intracranial arteries in Williams syndrome preserve normal patency.

PMID- 23868163
TI  - The medicare conversion factor.

PMID- 23868162
TI  - Cerebral aneurysms treated with flow-diverting stents: computational models with
      intravascular blood flow measurements.
AB  - BACKGROUND AND PURPOSE: Computational fluid dynamics modeling is useful in the
      study of the hemodynamic environment of cerebral aneurysms, but patient-specific
      measurements of boundary conditions, such as blood flow velocity and pressure,
      have not been previously applied to the study of flow-diverting stents. We
      integrated patient-specific intravascular blood flow velocity and pressure
      measurements into computational models of aneurysms before and after treatment
      with flow-diverting stents to determine stent effects on aneurysm hemodynamics.
      MATERIALS AND METHODS: Blood flow velocity and pressure were measured in peri
      aneurysmal locations by use of an intravascular dual-sensor pressure and Doppler
      velocity guidewire before and after flow-diverting stent treatment of 4
      unruptured cerebral aneurysms. These measurements defined inflow and outflow
      boundary conditions for computational models. Intra-aneurysmal flow rates, wall
      shear stress, and wall shear stress gradient were calculated. RESULTS:
      Measurements of inflow velocity and outflow pressure were successful in all 4
      patients. Computational models incorporating these measurements demonstrated
      significant reductions in intra-aneurysmal wall shear stress and wall shear
      stress gradient and a trend in reduced intra-aneurysmal blood flow. CONCLUSIONS:
      Integration of intravascular dual-sensor guidewire measurements of blood flow
      velocity and blood pressure provided patient-specific computational models of
      cerebral aneurysms. Aneurysm treatment with flow-diverting stents reduces blood
      flow and hemodynamic shear stress in the aneurysm dome.

PMID- 23868164
TI  - Endovascular treatment of distal anterior cerebral artery aneurysms: single
      center experience and a systematic review.
AB  - In this study, a single center's experience of 20 patients and a systematic
      review and a meta-analysis of 16 studies, including 279 patients/aneurysms,
      assessed the safety and efficacy of endovascular treatment of distal anterior
      cerebral artery aneurysms. The authors conclude that endovascular treatment of
      distal anterior cerebral artery aneurysms is associated with high angiographic
      occlusion rates, but the complication rates are higher compared with other
      aneurysms in the circle of Willis.

PMID- 23868165
TI  - MRI findings in autoimmune voltage-gated potassium channel complex encephalitis
      with seizures: one potential etiology for mesial temporal sclerosis.
AB  - BACKGROUND AND PURPOSE: Autoimmune voltage-gated potassium channel complex
      encephalitis is a common form of autoimmune encephalitis. Patients with seizures
      due to this form of encephalitis commonly have medically intractable epilepsy and
      may require immunotherapy to control seizures. It is important that radiologists
      recognize imaging characteristics of this type of autoimmune encephalitis and
      suggest it in the differential diagnosis because this seizure etiology is likely
      under-recognized. Our purpose was to characterize MR imaging findings in this
      patient population. MATERIALS AND METHODS: MR imaging in 42 retrospectively
      identified patients (22 males; median age, 56 years; age range, 8-79 years) with
      seizures and voltage-gated potassium channel complex autoantibody seropositivity
      was evaluated for mesial and extratemporal swelling and/or atrophy, T2
      hyperintensity, restricted diffusion, and enhancement. Statistical analysis was
      performed. RESULTS: Thirty-three of 42 patients (78.6%) demonstrated enlargement
      and T2 hyperintensity of mesial temporal lobe structures at some time point.
      Mesial temporal sclerosis was commonly identified (16/33, 48.5%) at follow-up
      imaging. Six of 9 patients (66.7%, P = .11) initially demonstrating hippocampal
      enhancement and 8/13 (61.5%, P = .013) showing hippocampal restricted diffusion
      progressed to mesial temporal sclerosis. Conversely, in 6 of 33 patients,
      abnormal imaging findings resolved. CONCLUSIONS: Autoimmune voltage-gated
      potassium channel complex encephalitis is frequently manifested as enlargement,
      T2 hyperintensity, enhancement, and restricted diffusion of the mesial temporal
      lobe structures in the acute phase. Recognition of these typical imaging findings
      may help prompt serologic diagnosis, preventing unnecessary invasive procedures
      and facilitating early institution of immunotherapy. Serial MR imaging may
      demonstrate resolution or progression of radiologic changes, including
      development of changes involving the contralateral side and frequent development
      of mesial temporal sclerosis.

PMID- 23868166
TI  - Prevalence of subdural collections in children with macrocrania.
AB  - BACKGROUND AND PURPOSE: The relationship between enlarged subarachnoid spaces and
      subdural collections is poorly understood and creates challenges for clinicians
      investigating the etiology of subdural collections. The purpose of this study was
      to determine the prevalence of subdural collections on cross sectional imaging in
      children with macrocephaly correlating with subarachnoid space enlargement.
      MATERIALS AND METHODS: The radiology information system of a large pediatric
      medical center was reviewed for "macrocrania" and "macrocephaly" on reports of
      cranial MRI/CT examinations in children <24 months of age, over a 24-month
      period. Head circumference was obtained from the clinical record. Studies were
      reviewed blindly for subdural collection presence and subarachnoid space size.
      Children with prior cranial surgery, parenchymal abnormalities, hydrocephalus, or
      conditions predisposing to parenchymal volume loss were excluded. Chart review
      was performed on those with subdural collections. RESULTS: Imaging from 177
      children with enlarged head circumference was reviewed. Nine were excluded, for a
      final cohort of 168 subjects (108 with enlarged subarachnoid space). Subdural
      collections were identified in 6 (3.6%), all with enlarged subarachnoid space
      (6/108, 5.6%). In 4, subdural collections were small, homogeneous, and
      nonhemorrhagic. In 2, the collections were complex (septations or hemorrhage).
      Two children were reported as victims of child abuse (both with complex
      collections). No definitive etiology was established in the other cases.
      CONCLUSIONS: The prevalence of subdural collections in imaged children with
      macrocrania was 3.6%, all occurring in children with enlarged subarachnoid space.
      Our results suggest that enlarged subarachnoid space can be associated with some
      subdural collections in this cohort. Despite this, we believe that unexpected
      subdural collections in children should receive close clinical evaluation for
      underlying causes, including abusive head trauma.

PMID- 23868167
TI  - The "peeking" effect in supervised feature selection on diffusion tensor imaging
      data.

PMID- 23868169
TI  - Integration under the big tent.

PMID- 23868168
TI  - An algorithm for calculating the probability of classes of data patterns on a
      genealogy.
AB  - Felsenstein's pruning algorithm allows one to calculate the probability of any
      particular data pattern arising on a phylogeny given a model of character
      evolution. Here we present a similar dynamic programming algorithm. Our algorithm
      treats the tree and model as known. The algorithm makes it feasible to calculate
      the probability that a randomly selected character will be a member of a
      particular class of character patterns. Specifically, we are interested in
      binning patterns by the number of parsimony steps and the set of states observed
      at the tips of the tree. This algorithm was developed to expand the range of data
      set sizes that can be used with Waddell et al.'s marginal testing approach for
      assessing the adequacy of a model. The algorithms introduced can also be used in
      likelihood calculations which correct for ascertainment biases. For example,
      Lewis introduced an Mkv model which corrects for the lack of constant sites. The
      probability of a constant pattern arising can be calculated using the algorithm
      that we present, or by enumerating all possible constant patterns and calculating
      the probability of each one. Because the number of constant data patterns is
      small, both methods are efficient. However, elaborations of the Mkv model (such
      as those in Nylander et al) require calculating the probability of parsimony
      uninformative patterns arising. For large trees and characters with many possible
      character states, the number of possible parismony-uninformative patterns is
      immense. In these cases, the algorithms introduced here will be more efficient.
      The algorithm has been implemented in open source software written in C++. 

PMID- 23868170
TI  - European pliopithecid diets revised in the light of dental microwear in
      Pliopithecus canmatensis and Barberapithecus huerzeleri.
AB  - Pliopithecinae and Crouzeliinae (Primates: Pliopithecidae) are distinguished
      dentally by the sharper crests, more compressed cusps, larger foveae, and
      narrower molars of the latter. Traditionally, such differences were qualitatively
      related to increased folivory in crouzeliines. This was subsequently disproved by
      microwear and shearing crest analyses, indicating that all pliopithecids were
      soft-fruit eaters, except for the more folivorous crouzeliine Barberapithecus.
      This seems however at odds with the occlusal morphology of the latter,
      intermediate between those of Pliopithecus and the more derived crouzeliine
      Anapithecus. To further assess dietary evolution in this group, we report results
      of dental microwear for two Iberian pliopithecids: Pliopithecus canmatensis, from
      several Abocador de Can Mata localities (11.8-11.7 Ma, MN8), and Barberapithecus
      huerzeleri from Castell de Barbera (ca. 11.2-10.5 Ma, MN8, or MN9). Contrary to
      previously published results, our analyses suggest that all pliopithecids,
      including Barberapithecus, had a frugivorous diet with a significant sclerocarpic
      component-apparently more marked in some pliopithecines (such as P. canmatensis)
      than in the crouzeliine Anapithecus. If our interpretation is correct, it would
      mean that, within the framework of a frugivorous diet with some hard-object
      feeding, crouzeliine dental evolution would have been driven by selection
      pressures towards increased soft-fruit consumption instead of folivory. Dental
      differences between pliopithecids and hominoids with a significant sclerocarpic
      component (i.e., orangutans) might be related to phylogenetic constraints,
      different food-processing methods and/or fracture toughness of hard foods
      consumed. Although additional research would be required, results suggest that
      dietary niche partitioning played a significant role in the radiation of European
      pliopithecids.

PMID- 23868171
TI  - Male genetic structure and paternity in western lowland gorillas (Gorilla gorilla
      gorilla).
AB  - The male dispersal patterns of western lowland gorillas (WLGs, Gorilla gorilla
      gorilla) are not well understood. To determine whether most silverbacks stay
      close to their relatives, we analyzed autosomal and Y-chromosomal microsatellites
      (STRs) in wild WLGs at Moukalaba, Gabon. We obtained STR genotypes for 38
      individuals, including eight silverbacks and 12 adult females in an approximately
      40 km(2) area. Among them, 20 individuals were members of one identified group
      (Group Gentil; GG), including one silverback and six adult females. The
      silverback sired all 13 of the offspring in GG and no Y-STR polymorphism within
      GG was found, as expected in a one-male group structure. Over all silverbacks
      sampled, Y-STR diversity was high considering the limited sampling area, and
      silverbacks with similar Y-STR haplotypes were not always located in nearby
      areas. Although the misclassification rate of kinship estimates in this study was
      not negligible, there were no kin dyads among all silverbacks sampled. These
      results suggest that silverbacks born in the same group do not stay close to each
      other after maturation. The Y-STR diversity in this study was similar to that of
      a previous study conducted in an area that was approximately 150 times larger
      than our study area. Similarity of WLG Y-STR diversity between studies at
      different sampling scales suggests that male gene flow may not be geographically
      limited. These results suggest that WLG males normally disperse from their natal
      areas after maturation, at least, in Moukalaba.

PMID- 23868172
TI  - Diet and social status on Taumako, a Polynesian outlier in the Southeastern
      Solomon Islands.
AB  - Stable isotopes (delta(13)C, delta(15)N, and delta(34)S) are used to characterize
      the diet of the adult individuals (n = 99) interred in the Namu burial ground
      located on the Polynesian outlier of Taumako (~300-750 BP). Polynesian outliers
      are islands on the fringe of Remote Oceania that were inhabited by a back
      migration of populations from Polynesia during prehistory. As a result of
      admixture with nearby island communities, little is known about the social
      structure and social diversity of the prehistoric inhabitants of Taumako. The
      distribution of prestige grave goods within the Namu cemetery has been used as
      evidence to support the premise that Taumakoan social structure was stratified
      like Polynesian societies. Here we test the hypothesis that "wealthy" individuals
      and males will display isotopic ratios indicative of the consumption of "high
      status" foods in the Pacific islands such as pork, chicken, sea turtle, and
      pelagic fish. The isotope results suggest the delta(34) S values were
      diagenetically altered, possibly an effect of volcanism. The carbon and nitrogen
      stable isotope ratios indicate that the diet of all the individuals included a
      mixture of C3 terrestrial plant foods (likely starchy staples such as yam, taro,
      and breadfruit, in addition to nuts) and a variety of marine resources, including
      reef and pelagic fish. The stable isotope results indicate that wealthy
      individuals and males were eating more foods from higher trophic levels,
      interpreted as being high status animal foods. The socially differentiated food
      consumption patterns are discussed within a Pacific island context.

PMID- 23868173
TI  - Weaning at Anglo-Saxon Raunds: Implications for changing breastfeeding practice
      in Britain over two millennia.
AB  - This study investigated stable-isotope ratio evidence of weaning for the late
      Anglo-Saxon population of Raunds Furnells, Northamptonshire, UK. delta(15)N and
      delta(13)C values in rib collagen were obtained for individuals of different ages
      to assess the weaning age of infants within the population. A peak in delta(15) N
      values at about 2-year-old, followed by a decline in delta(15) N values until age
      three, indicates a change in diet at that age. This change in nitrogen isotope
      ratios corresponds with the mortality profile from the site, as well as with
      archaeological and documentary evidence on attitudes towards juveniles in the
      Anglo-Saxon period. The pattern of delta(13) C values was less clear. Comparison
      of the predicted age of weaning to published data from sites dating from the Iron
      Age to the 19th century in Britain reveals a pattern of changing weaning
      practices over time, with increasingly earlier commencement and shorter periods
      of complementary feeding in more recent periods. Such a change has implications
      for the interpretation of socioeconomic changes during this period of British
      history, since earlier weaning is associated with decreased birth spacing, and
      could thus have contributed to population growth.

PMID- 23868174
TI  - New craniodental fossils of papionin monkeys from Cooper's D, South Africa.
AB  - Papionin monkey fossils are common in the Plio-Pleistocene aged karst cave
      deposits northwest of Johannesburg in South Africa. These deposits have yielded
      important primate and other vertebrate fauna since their discovery in the early
      part of the 20th century. In this article, we describe new primate cranial and
      dental specimens from excavations at the site of Cooper's D in the Sterkfontein
      Valley that date to around 1.5 million years ago. Unlike other localities in
      southern Africa, most of the new fossils are referred to Theropithecus oswaldi
      oswaldi, an extinct gramnivorous monkey related to the living gelada. Diagnostic
      features of T. o. oswaldi crania and teeth include large, thickly enameled molars
      with tall, columnar cusps, and high molar relief, an upright mandibular ramus,
      postorbital constriction, and anterior fusion of temporal lines. Also present in
      the new sample are teeth referred to Papio sp., which show low crowned bunodont
      molars, and a number of indeterminate papionin teeth and skull fragments. The
      presence of T. o. oswaldi at Cooper's D extends the list of known localities
      where the taxon is found, and may indicate the presence of an open, grassland
      environment in the area during the early Pleistocene. The abundance of theropith
      fossils at Cooper's suggests that Papio was not consistently the most common
      papionin in southern Africa over the past three million years.

PMID- 23868175
TI  - Postnatal temporal bone ontogeny in Pan, Gorilla, and Homo, and the implications
      for temporal bone ontogeny in Australopithecus afarensis.
AB  - Assessments of temporal bone morphology have played an important role in
      taxonomic and phylogenetic evaluations of fossil taxa, and recent three
      dimensional analyses of this region have supported the utility of the temporal
      bone for testing taxonomic and phylogenetic hypotheses. But while clinical
      analyses have examined aspects of temporal bone ontogeny in humans, the ontogeny
      of the temporal bone in non-human taxa is less well documented. This study
      examines ontogenetic allometry of the temporal bone in order to address several
      research questions related to the pattern and trajectory of temporal bone shape
      change during ontogeny in the African apes and humans. We further apply these
      data to a preliminary analysis of temporal bone ontogeny in Australopithecus
      afarensis. Three-dimensional landmarks were digitized on an ontogenetic series of
      specimens of Homo sapiens, Pan troglodytes, Pan paniscus, and Gorilla gorilla.
      Data were analyzed using geometric morphometric methods, and shape changes
      throughout ontogeny in relation to size were compared. Results of these analyses
      indicate that, despite broadly similar patterns, African apes and humans show
      marked differences in development of the mandibular fossa and tympanic portions
      of the temporal bone. These findings indicate divergent, rather than parallel,
      postnatal ontogenetic allometric trajectories for temporal bone shape in these
      taxa. The pattern of temporal bone shape change with size exhibited by A.
      afarensis showed some affinities to that of humans, but was most similar to
      extant African apes, particularly Gorilla.

PMID- 23868176
TI  - Brief communication: Evolution of a specific O allele (O1vG542A) supports unique
      ancestry of Native Americans.
AB  - In this study, we explore the geographic and temporal distribution of a unique
      variant of the O blood group allele called O1v(G542A) , which has been shown to
      be shared among Native Americans but is rare in other populations. O1v(G542A) was
      previously reported in Native American populations in Mesoamerica and South
      America, and has been proposed as an ancestry informative marker. We investigated
      whether this allele is also found in the Tlingit and Haida, two contemporary
      indigenous populations from Alaska, and a pre-Columbian population from
      California. If O1v(G542A) is present in Na-Dene speakers (i.e., Tlingits), it
      would indicate that Na-Dene speaking groups share close ancestry with other
      Native American groups and support a Beringian origin of the allele, consistent
      with the Beringian Incubation Model. If O1v(G542A) is found in pre-Columbian
      populations, it would further support a Beringian origin of the allele, rather
      than a more recent introduction of the allele into the Americas via gene flow
      from one or more populations which have admixed with Native Americans over the
      past five centuries. We identified this allele in one Na-Dene population at a
      frequency of 0.11, and one ancient California population at a frequency of 0.20.
      Our results support a Beringian origin of O1v(G542A) , which is distributed today
      among all Native American groups that have been genotyped in appreciable numbers
      at this locus. This result is consistent with the hypothesis that Na-Dene and
      other Native American populations primarily derive their ancestry from a single
      source population.

PMID- 23868177
TI  - Technical note: Quantification of neurocranial shape variation using the shortest
      paths connecting pairs of anatomical landmarks.
AB  - Three-dimensional geometric morphometric techniques have been widely used in
      quantitative comparisons of craniofacial morphology in humans and nonhuman
      primates. However, few anatomical landmarks can actually be defined on the
      neurocranium. In this study, an alternative method is proposed for defining semi
      landmarks on neurocranial surfaces for use in detailed analysis of cranial shape.
      Specifically, midsagittal, nuchal, and temporal lines were approximated using
      Bezier curves and equally spaced points along each of the curves were defined as
      semi-landmarks. The shortest paths connecting pairs of anatomical landmarks as
      well as semi-landmarks were then calculated in order to represent the surface
      morphology between landmarks using equally spaced points along the paths. To
      evaluate the efficacy of this method, the previously outlined technique was used
      in morphological analysis of sexual dimorphism in modern Japanese crania. The
      study sample comprised 22 specimens that were used to generate 110 anatomical
      semi-landmarks, which were used in geometric morphometric analysis. Although
      variations due to sexual dimorphism in human crania are very small, differences
      could be identified using the proposed landmark placement, which demonstrated the
      efficacy of the proposed method.

PMID- 23868179
TI  - HPLC and chemometrics for the quality consistency evaluation of Shuanghuanglian
      injection.
AB  - A high-performance liquid chromatography method with diode array detection was
      developed for simultaneous analysis of organic acids (chlorogenic acid, caffeic
      acid, 4,5-dicaffeoylquinic acid) and flavonoids (baicalin, baicalein, wogonin) in
      Shuang-huang-lian injection, a traditional Chinese medicine being prescribed
      widely for anti-bacterial, anti-viral and immunostimulant activity. All
      calibration curves showed good linear correlation (r(2) > 0.9997) within the test
      ranges. Validation proved that the repeatability of the method was good and
      recovery was satisfactory. The validated method was successfully applied to 24
      batches of Shuang-huang-lian injection. The result showed that there was a great
      variation among different samples. Principal component analysis further proved
      considerable variations among the samples from eight manufacturers, and suggested
      that chlorogenic acid and baicalin might have the greatest variations among the
      24 batches. In conclusion, these results demonstrated that the method proposed
      was very useful for the analysis and quality consistency evaluation of Shuang
      huang-lian injection. 

PMID- 23868178
TI  - Distinct patterns of DNA methylation in conventional adenomas involving the right
      and left colon.
AB  - Recent studies have shown two distinct non-CIMP methylation clusters in
      colorectal cancer, raising the possibility that DNA methylation, involving non
      CIMP genes, may play a role in the conventional adenoma-carcinoma pathway. A
      total of 135 adenomas (65 left colon and 70 right colon) were profiled for
      epigenome-wide DNA methylation using the Illumina HumanMethylation450 BeadChip. A
      principal components analysis was performed to examine the association between
      variability in DNA methylation and adenoma location. Linear regression and linear
      mixed effects models were used to identify locus-specific differential DNA
      methylation in adenomas of right and left colon. A significant association was
      present between the first principal component and adenoma location (P=0.007),
      even after adjustment for subject age and gender (P=0.009). A total of 168 CpG
      sites were differentially methylated between right- and left-colon adenomas and
      these loci demonstrated enrichment of homeobox genes (P=3.0 * 10(-12)). None of
      the 168 probes were associated with CIMP genes. Among CpG loci with the largest
      difference in methylation between right- and left-colon adenomas, probes
      associated with PRAC (prostate cancer susceptibility candidate) gene showed
      hypermethylation in right-colon adenomas whereas those associated with CDX2
      (caudal type homeobox transcription factor 2) showed hypermethylation in left
      colon adenomas. A subgroup of left-colon adenomas enriched for current smokers
      (OR=6.1, P=0.004) exhibited a methylation profile similar to right-colon
      adenomas. In summary, our results indicate distinct patterns of DNA methylation,
      independent of CIMP genes, in adenomas of the right and left colon. 

PMID- 23868180
TI  - Reflux venous flow in dural sinus and internal jugular vein on 3D time-of-flight
      MR angiography.
AB  - INTRODUCTION: Reflux venous signal on the brain and neck time-of-flight magnetic
      resonance angiography (TOF MRA) is thought to be related to a compressed left
      brachiocephalic vein. This study is aimed to assess the prevalence of venous
      reflux flow in internal jugular vein (IJV), sigmoid sinus/transverse sinus
      (SS/TS), and inferior petrosal sinus (IPS) on the brain and neck TOF MRA and its
      pattern. METHODS: From the radiology database, 3,475 patients (1,526 men, 1,949
      women, age range 19-94, median age 62 years) with brain and neck standard 3D TOF
      MRA at 3 T and 1.5 T were identified. Rotational maximal intensity projection
      images of 3D TOF MRA were assessed for the presence of reflux flow in IJV, IPS,
      and SS/TS. RESULTS: Fifty-five patients (1.6%) had reflux flow, all in the left
      side. It was more prevalent in females (n = 43/1,949, 2.2%) than in males (n =
      12/1,526, 0.8%) (p = 0.001). The mean age of patients with reflux flow (66 years
      old) was older than those (60 years old) without reflux flow (p = 0.001). Three
      patients had arteriovenous shunt in the left arm for hemodialysis. Of the
      remaining 52 patients, reflux was seen on IJV in 35 patients (67.3%). There were
      more patients with reflux flow seen on SS/TS (n = 34) than on IPS (n = 25).
      CONCLUSION: Venous reflux flow on TOF MRA is infrequently observed, and reflux
      pattern is variable. Because it is exclusively located in the left side, the
      reflux signal on TOF MRA could be an alarm for an undesirable candidate for a
      contrast injection on the left side for contrast-enhanced imaging study.

PMID- 23868181
TI  - Constitutive activation of distinct NF-kappaB signals in EBV-associated
      nasopharyngeal carcinoma.
AB  - As a distinct type of head and neck cancer, non-keratinizing nasopharyngeal
      carcinoma (NPC) is closely associated with EBV infection and massive lymphoid
      infiltration. The unique histological features suggest that local inflammation
      plays an important role in NPC tumourigenesis. We comprehensively characterized
      NF-kappaB signalling, a key inflammatory pathway which might contribute to the
      tumourigenesis of this EBV-associated cancer. By EMSA, western blotting, and
      immunohistochemical staining, constitutive activation of distinct NF-kappaB
      complexes, either p50/p50/Bcl3 or p50/RelB, was found in almost all EBV-positive
      NPC tumours. siRNA or chemical inhibition of NF-kappaB signalling significantly
      inhibited the growth of EBV-positive NPC cells C666-1. Gene expression profiling
      identified a number of NF-kappaB target genes involved in cell proliferation,
      apoptosis, immune response, and transcription. We further confirmed that p50
      signals modulate the expression of multiple oncogenes (MYB, BCL2), chemokines,
      and chemokine receptors (CXCL9, CXCL10, CX3CL1, and CCL20). The findings support
      a crucial role of these constitutively activated NF-kappaB signals in NPC
      tumourigenesis and local inflammation. In addition to expression of the viral
      oncoprotein LMP1, genetic alteration of several NF-kappaB regulators (eg TRAF3,
      TRAF2, NFKBIA, A20) also contributes to the aberrant NF-kappaB activation in EBV
      associated NPC. Except for LMP1-expressing C15 cells, all NPC tumour lines
      harbour at least one of these genetic alterations. Importantly, missense
      mutations of TRAF3, TRAF2, and A20 were also detected in 3/33 (9.1%) primary
      tumours. Taken together with the reported LTBR amplification in 7.3% of primary
      NPCs, genetic alterations in NF-kappaB pathways occurred in at least 16% of cases
      of this cancer. The findings indicate that distinct NF-kappaB signals are
      constitutively activated in EBV-positive NPC cells by either multiple genetic
      changes or EBV latent genes.

PMID- 23868182
TI  - Synthesis of spiro[indoline-3,1'-quinolizines] and spiro[indoline-3, 4'
      pyrido[1,2-a]quinolines] via three-component reactions of azaarenes,
      acetylenedicarboxylate, and 3-methyleneoxindoles.
AB  - The three-component reactions of substituted pyridines, dimethyl
      acetylenedicarboxylates, and 3-phenacylideneoxindoles afforded spiro[indoline
      3,1'quinolizines] in high yields and with high diastereoselectivity. The Diels
      Alder reactions of spiro[indoline-3,1' quinolizines] with maleic anhydride and N-
      phenyl maleimides successfully resulted in polyfunctionalized isoquinolinuclidine
      derivatives. The similar three-component reactions with quinoline resulted in the
      novel spiro[indoline-3,4' -pyrido[1,2-a]quinolines] in moderate to good yields.

PMID- 23868183
TI  - Palladium-catalyzed regioselective synthesis of 2(2'-biphenyl)benzimidazoles
      through C-H activation.
AB  - An efficient palladium-catalyzed strategy through C-H bond activation for the
      synthesis of 2(2[Formula: see text]-biphenyl)-benzimidazoles is reported herein.
      The regioselective C-C bond formation proceeds in a sealed tube via oxidative C-H
      activation of ortho-directed 2-aryl-benzimidazole to couple with various
      iodobenzene analogs in high yields. This arylation exhibited high
      regioselectivity which is able to increase molecular diversity in difficult
      functionalized positions of parent molecules. This strategy provides a convenient
      and simple synthesis of biphenyl heterocyclic compounds with high
      regioselectivity. 

PMID- 23868184
TI  - Cyclohexyl iodide promoted approach for coumarin analog synthesis using small
      scaffold.
AB  - New chemical approaches were adopted for the synthesis of biologically important
      coumarins utilizing cyclohexane-1,3-dione derivatives as novel scaffold which
      were prepared from acetone and ethyl acrylate following our previous report. The
      stepwise strategies of aromatization, dehydrogenation, and demethylative
      cyclization were followed for coumarins synthesis from cyclohexane-1,3-dione
      derivatives. This work reports the first time cyclohexyl iodide was used for the
      demethylative cyclization reaction of [Formula: see text]-diaryl acrylates for 4
      arylcoumarins synthesis.

PMID- 23868185
TI  - Native multipotential stromal cell colonization and graft expander potential of a
      bovine natural bone scaffold.
AB  - Graft expanders are bone scaffolds used, in combination with autografts, to fill
      large bone defects in trauma surgery. This study investigates the graft expander
      potential of a natural bone substitute Orthoss by studying its ability to support
      attachment, growth and osteogenic differentiation of neighboring multipotential
      stromal cells (MSCs). Material consisting of bone marrow (BM) aspirate and reamer
      irrigator-aspirator (RIA)-harvested autograft bone was co-cultured with
      commercially available Orthoss granules. Native MSCs attached to Orthoss were
      expanded and phenotypically characterized. MSCs egress from neighboring cancelous
      bone was assessed in 3D Matrigel co-cultures. MSC differentiation was evaluated
      using scanning electron microscopy and measuring alkaline phosphatase (ALP)
      activity per cell. CD45(+) hematopoietic lineage cells and highly proliferative
      CD90(+) CD73(+) CD105(+) MSCs preferentially colonized Orthoss granules, over RIA
      bone chips. MSC colonization was followed by their intrinsic osteogenic
      differentiation, assessed as mineral deposition and gradual rise in ALP activity,
      even in the absence of osteogenic stimuli. When in contact with mixed cell
      populations and RIA chips, Orthoss granules support the attachment, growth and
      osteogenic differentiation of neighboring MSCs. Therefore, natural bone
      substitutes similar to Orthoss can be used as void fillers and graft expanders
      for repairing large bone defects in conjunction with autologous BM aspirates and
      autografts.

PMID- 23868187
TI  - Coexistence of ipsilateral pain-inhibitory and facilitatory processes after high
      frequency electrical stimulation.
AB  - BACKGROUND: High-frequency electrical stimulation (HFS) of the human forearm
      evokes analgesia to blunt pressure in the ipsilateral forehead, consistent with
      descending ipsilateral inhibitory pain modulation. The aim of the current study
      was to further delineate pain modulation processes evoked by HFS by examining
      sensory changes in the arm and forehead; investigating the effects of HFS on
      nociceptive blink reflexes elicited by supraorbital electrical stimulation; and
      assessing effects of counter-irritation (electrically evoked pain at the HFS
      conditioned site in the forearm) on nociceptive blink reflexes before and after
      HFS. METHODS: Before and after HFS conditioning, sensitivity to heat and to blunt
      and sharp stimuli was assessed at and adjacent to the conditioned site in the
      forearm and on each side of the forehead. Nociceptive blink reflexes were also
      assessed before and after HFS with and without counter-irritation of the forearm.
      RESULTS: HFS triggered secondary hyperalgesia in the forearm (a sign of central
      sensitization) and analgesia to blunt pressure in the ipsilateral forehead. Under
      most conditions, both HFS conditioning and counter-irritation of the forearm
      suppressed electrically evoked pain in the forehead, and the amplitude of the
      blink reflex to supraorbital stimuli decreased. Importantly, however, in the
      absence of forearm counter-irritation, HFS conditioning facilitated ipsilateral
      blink reflex amplitude to supraorbital stimuli delivered ipsilateral to the HFS
      conditioned site. CONCLUSIONS: These findings suggest that HFS concurrently
      triggers hemilateral inhibitory and facilitatory influences on nociceptive
      processing over and above more general effects of counter-irritation. The
      inhibitory influence may help limit the spread of sensitization in central
      nociceptive pathways.

PMID- 23868186
TI  - Structural study of the partially disordered full-length delta subunit of RNA
      polymerase from Bacillus subtilis.
AB  - The partially disordered delta subunit of RNA polymerase was studied by various
      NMR techniques. The structure of the well-folded N-terminal domain was determined
      based on inter-proton distances in NOESY spectra. The obtained structural model
      was compared to the previously determined structure of a truncated construct
      (lacking the C-terminal domain). Only marginal differences were identified, thus
      indicating that the first structural model was not significantly compromised by
      the absence of the C-terminal domain. Various (15) N relaxation experiments were
      employed to describe the flexibility of both domains. The relaxation data
      revealed that the C-terminal domain is more flexible, but its flexibility is not
      uniform. By using paramagnetic labels, transient contacts of the C-terminal tail
      with the N-terminal domain and with itself were identified. A propensity of the C
      terminal domain to form beta-type structures was obtained by chemical shift
      analysis. Comparison with the paramagnetic relaxation enhancement indicated a
      well-balanced interplay of repulsive and attractive electrostatic interactions
      governing the conformational behavior of the C-terminal domain. The results
      showed that the delta subunit consists of a well-ordered N-terminal domain and a
      flexible C-terminal domain that exhibits a complex hierarchy of partial ordering.

PMID- 23868188
TI  - A Phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride
      with weekly paclitaxel in metastatic breast cancer.
AB  - Tivozanib is a potent selective tyrosine kinase inhibitor (TKI) of vascular
      endothelial growth factor receptors (VEGFRs) 1, 2, and 3. This Phase Ib study
      investigated the safety/tolerability, pharmacokinetics (PK), and activity of
      tivozanib with weekly paclitaxel in metastatic breast cancer (MBC). MBC patients
      with no prior VEGFR TKI treatment received daily oral tivozanib (3 weeks on, 1
      week off) with weekly paclitaxel 90 mg/m(2). Standard 3 + 3 dose escalation was
      used; tivozanib cohorts (C) included C1 0.5 mg, C2 1.0 mg, and C3 1.5 mg.
      Assessments included Response Evaluation Criteria in Solid Tumors response, PK,
      and vascular function. Eighteen patients enrolled. Toxicities in >20 % of
      patients included fatigue, alopecia, nausea, diarrhea, peripheral sensory
      neuropathy, and hypertension. Grade 3/4 toxicities in >15 % of patients included
      fatigue and neutropenia. Maximum tolerated dose was tivozanib 1.5 mg with
      paclitaxel 90 mg/m(2). Four patients withdrew because of toxicity and one due to
      progressive disease. Thirteen patients were evaluable for response: four (30.8 %)
      had confirmed partial response; four had stable disease >=6 months (30.8 %). PK
      data suggest no influence of paclitaxel on tivozanib concentrations. Tivozanib
      plus weekly paclitaxel was tolerable at all dose levels, supporting their
      combination at full dose. Activity in this small population was encouraging. 

PMID- 23868189
TI  - Genetic determinants of aromatase inhibitor-related arthralgia: the B-ABLE cohort
      study.
AB  - A major side effect of aromatase inhibitor (AI) therapy is AI-related arthralgia
      (AIA), which often leads to therapy discontinuation. We aimed to identify genetic
      variants associated with AIA and therapy discontinuation in the first year of AI
      treatment. Our prospective cohort study included 343 postmenopausal women with
      early breast cancer starting AI therapy. Single nucleotide polymorphisms (SNPs)
      in candidate genes involved in estrogen and vitamin D signaling were selected.
      Univariate and multivariate linear/logistic regressions were fitted in order to
      asses the association between studied SNPs and AIA intensity (visual analogic
      scale score) at 3 and 12 months of follow-up, worsening pain, and therapy
      discontinuation. We also tested for a priori-defined interactions by introducing
      multiplicative terms in the regression equations. SNPs in CYP17A1 and VDR genes
      appeared significantly associated with AIA (P = 0.003, P = 0.012, respectively).
      One SNP in CYP27B1 gene was related to therapy discontinuation [P = 0.02; OR 0.29
      (0.09-0.99)]. We revealed interactions between CYP27B1 and both CYP17A1 (P =
      0.01) and VDR SNPs (P = 0.06). Furthermore, an additive effect on pain intensity
      was shown for unfavorable alleles, with two points higher mean absolute pain
      increase and up to 5.3-fold higher risk of worsening pain compared to favorable
      genotypes. SNPs in CYP17A1, VDR, and CYP27B1 genes predict the risk of AIA. Their
      determination would be useful to trigger the monitoring strategies in women at
      risk of therapy discontinuation. 

PMID- 23868190
TI  - What is the evidence for the use of acupuncture as an intervention for symptom
      management in cancer supportive and palliative care: an integrative overview of
      reviews.
AB  - PURPOSE: This study aims to systematically appraise the evidence for the use of
      acupuncture for symptom management in cancer and supportive care and to identify
      recommendations for clinical practice and future research. METHODS: A systematic
      search was carried out to identify reviews of the use of acupuncture in cancer
      supportive and palliative care, using MEDLINE, EMBASE, CINAHL, Web of Science,
      Cochrane Library, British Nursing Index, Index to Theses, Dissertations and
      Theses (via Proquest) and NHS evidence. Search terms included: acupuncture,
      cancer and symptoms. Data were extracted for analysis. Reviews were assessed for
      quality using a five-item checklist but were not excluded from the review on
      grounds of quality, in order to include a comprehensive scope of the subject.
      RESULTS: Seventeen reviews were included in the review. Evidence was found for
      the use of acupuncture for treatment-related nausea and vomiting. Benefit was
      reported for other cancer-related symptoms, including pain, fatigue, hot flushes,
      xerostomia, dyspnoea and anxiety. Reviewers found a paucity of rigorous trials
      and heterogeneity of populations, interventions, controls and outcome measures,
      which challenge the process of systematic review and meta-analysis. CONCLUSION:
      Acupuncture should be considered for symptom management where there are limited
      treatment options, using current peer-reviewed guidelines and clinical reasoning.
      Much of the primary research reported in reviews is innovative and indicates
      potential benefit for people with cancer-related symptoms. The complexity of
      acupuncture as an intervention needs to be acknowledged in future research
      designs and when reviewing research findings. An iterative approach using
      adequate interventions, appropriate outcome measures and adherence to reporting
      standards is required to evaluate the efficacy of acupuncture in cancer
      supportive and palliative care.

PMID- 23868191
TI  - Biomarkers of dairy fatty acids and risk of cardiovascular disease in the Multi
      ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Evidence regarding the role of dairy fat intake in cardiovascular
      disease (CVD) has been mixed and inconclusive. Most earlier studies have used
      self-reported measures of dietary intake and focused on relatively racially
      homogeneous populations. Circulating biomarkers of dairy fat in a multiethnic
      cohort provide objective measures of dairy fat intake and facilitate conclusions
      relevant to populations with different diets and susceptibility to CVD. METHODS
      AND RESULTS: In a multiethnic cohort of 2837 US adults aged 45 to 84 years at
      baseline (2000-2002), phospholipid fatty acids including 15:0, 14:0, and trans
      16:1n7 were measured using standardized methods, and the incidence of CVD
      prospectively adjudicated. Self-reported whole-fat dairy and butter intakes had
      strongest associations with 15:0, rather than 14:0 or trans-16:1n7. In
      multivariate models including demographics and lifestyle and dietary habits, each
      SD-unit of 15:0 was associated with 19% lower CVD risk (hazard ratio [95% CI]
      0.81 [0.68 to 0.98]) and 26% lower coronary heart disease (CHD) risk (0.74 [0.60
      to 0.92]). Associations were strengthened after mutual adjustment for 14:0 and
      trans-16:1n-7 and were similar after adjustment for potential mediators. Plasma
      phospholipid 14:0 and trans-16:1n-7 were not significantly associated with
      incident CVD or CHD. All findings were similar in white, black, Hispanic, and
      Chinese American participants. CONCLUSION: Plasma phospholipid 15:0, a biomarker
      of dairy fat, was inversely associated with incident CVD and CHD, while no
      association was found with phospholipid 14:0 and trans-16:1n-7. These findings
      support the need for further investigation of CVD effects of dairy fat, dairy
      specific fatty acids, and dairy products in general.

PMID- 23868192
TI  - Provider specialty and atrial fibrillation treatment strategies in United States
      community practice: findings from the ORBIT-AF registry.
AB  - BACKGROUND: The prevalence of atrial fibrillation (AF) continues to increase;
      however, there are limited data describing the division of care among
      practitioners in the community and whether care differs depending on provider
      specialty. METHODS AND RESULTS: Using the Outcomes Registry for Better Informed
      Treatment of AF (ORBIT-AF) Registry, we described patient characteristics and AF
      management strategies in ambulatory clinic practice settings, including
      electrophysiology (EP), general cardiology, and primary care. A total of 10 097
      patients were included; of these, 1544 (15.3%) were cared for by an EP provider,
      6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal
      medicine/primary care provider. Compared with those patients who were cared for
      by cardiologists or internal medicine/primary care providers, patients cared for
      by EP providers were younger (median age, 73 years [interquartile range, IQR, 64,
      80 years, Q1, Q3] versus 75 years [IQR, 67, 82 years] for cardiology and versus
      76 years [IQR, 68, 82 years] for primary care). Compared with cardiology and
      internal medicine/primary care providers, EP providers used rhythm control
      (versus rate control) management more often (44.2% versus 29.7% and 28.8%,
      respectively, P<0.0001; adjusted odds ratio [OR] EP versus cardiology, 1.66 [95%
      confidence interval, CI, 1.05 to 2.61]; adjusted OR for internal medicine/primary
      care versus cardiology, 0.91 [95% CI, 0.65 to 1.26]). Use of oral anticoagulant
      therapy was high across all providers, although it was higher for cardiology and
      EP providers (overall, 76.1%; P=0.02 for difference between groups). CONCLUSIONS:
      Our data demonstrate important differences between provider specialties, the
      demographics of the AF patient population treated, and treatment strategies
      particularly for rhythm control and anticoagulation therapy.

PMID- 23868194
TI  - Interleukin-10 producing-B cells and their association with responsiveness to
      rituximab in myasthenia gravis.
AB  - INTRODUCTION: A subset of regulatory B cells in humans and mice has been defined
      functionally by their ability to produce interleukin (IL)-10. We characterized IL
      10-producing B (B10) cells in myasthenia gravis (MG) patients and correlated them
      with disease activity and responsiveness to rituximab therapy. METHODS:
      Frequencies of B10 cells from MG patients and healthy controls were monitored by
      fluorescence-activated cell sorting (FACS). RESULTS: MG patients had fewer B10
      cells than controls, which was associated with more severe disease status.
      Moreover, patients who responded well to rituximab therapy exhibited rapid
      repopulation of B10 cells, whereas in patients who did not respond well to
      rituximab, B10 cell repopulation was delayed. The kinetics of B10 cells were
      related to the responsiveness to rituximab in MG. CONCLUSIONS: We have
      characterized a specific subset of B10 cells in MG patients which may serve as a
      marker for disease activity and responsiveness to immune therapy.

PMID- 23868196
TI  - Ordered mesoporous materials based on interfacial assembly and engineering.
AB  - Ordered mesoporous materials have inspired prominent research interest due to
      their unique properties and functionalities and potential applications in
      adsorption, separation, catalysis, sensors, drug delivery, energy conversion and
      storage, and so on. Thanks to continuous efforts over the past two decades, great
      achievements have been made in the synthesis and structural characterization of
      mesoporous materials. In this review, we summarize recent progresses in preparing
      ordered mesoporous materials from the viewpoint of interfacial assembly and
      engineering. Five interfacial assembly and synthesis are comprehensively
      highlighted, including liquid-solid interfacial assembly, gas-liquid interfacial
      assembly, liquid-liquid interfacial assembly, gas-solid interfacial synthesis,
      and solid-solid interfacial synthesis, basics about their synthesis pathways,
      princples and interface engineering strategies. 

PMID- 23868195
TI  - GC skew at the 5' and 3' ends of human genes links R-loop formation to epigenetic
      regulation and transcription termination.
AB  - Strand asymmetry in the distribution of guanines and cytosines, measured by GC
      skew, predisposes DNA sequences toward R-loop formation upon transcription.
      Previous work revealed that GC skew and R-loop formation associate with a core
      set of unmethylated CpG island (CGI) promoters in the human genome. Here, we show
      that GC skew can distinguish four classes of promoters, including three types of
      CGI promoters, each associated with unique epigenetic and gene ontology
      signatures. In particular, we identify a strong and a weak class of CGI promoters
      and show that these loci are enriched in distinct chromosomal territories
      reflecting the intrinsic strength of their protection against DNA methylation.
      Interestingly, we show that strong CGI promoters are depleted from the X
      chromosome while weak CGIs are enriched, a property consistent with the
      acquisition of DNA methylation during dosage compensation. Furthermore, we
      identify a third class of CGI promoters based on its unique GC skew profile and
      show that this gene set is enriched for Polycomb group targets. Lastly, we show
      that nearly 2000 genes harbor GC skew at their 3' ends and that these genes are
      preferentially located in gene-dense regions and tend to be closely arranged.
      Genomic profiling of R-loops accordingly showed that a large proportion of genes
      with terminal GC skew form R-loops at their 3' ends, consistent with a role for
      these structures in permitting efficient transcription termination. Altogether,
      we show that GC skew and R-loop formation offer significant insights into the
      epigenetic regulation, genomic organization, and function of human genes. 

PMID- 23868198
TI  - Remarkable alkaline stability of an engineered protein A as immunoglobulin
      affinity ligand: C domain having only one amino acid substitution.
AB  - Protein A affinity chromatography is the standard purification process for the
      capture of therapeutic antibodies. The individual IgG-binding domains of protein
      A (E, D, A, B, C) have highly homologous amino acid sequences. From a previous
      report, it has been assumed that the C domain has superior resistance to alkaline
      conditions compared to the other domains. We investigated several properties of
      the C domain as an IgG-Fc capture ligand. Based on cleavage site analysis of a
      recombinant protein A using a protein sequencer, the C domain was found to be the
      only domain to have neither of the potential alkaline cleavage sites. Circular
      dichroism (CD) analysis also indicated that the C domain has good physicochemical
      stability. Additionally, we evaluated the amino acid substitutions at the Gly-29
      position of the C domain, as the Z domain (an artificial B domain) acquired
      alkaline resistance through a G29A mutation. The G29A mutation proved to increase
      the alkaline resistance of the C domain, based on BIACORE analysis, although the
      improvement was significantly smaller than that observed for the B domain.
      Interestingly, a number of other amino acid mutations at the same position
      increased alkaline resistance more than did the G29A mutation. This result
      supports the notion that even a single mutation on the originally alkali-stable C
      domain would improve its alkaline stability. An engineered protein A based on
      this C domain is expected to show remarkable performance as an affinity ligand
      for immunoglobulin. 

PMID- 23868197
TI  - Restrictive eating behaviors are a nonweight-based marker of severity in anorexia
      nervosa.
AB  - OBJECTIVE: The purpose of this study was to compare the type and frequency of
      restrictive eating behaviors across the two subtypes of anorexia nervosa (AN;
      restricting [ANr] and binge eating/purging [ANbp]) using ecological momentary
      assessment (EMA) and to determine whether subtype differences in restrictive
      eating behaviors were attributable to severity of the disorder or the frequency
      of binge eating. METHOD: Participants (N = 118) were women at least 18 years of
      age with full (n = 59) or subthreshold (n = 59) AN who participated in a two week
      (EMA) protocol. RESULTS: General estimating equations revealed that individuals
      with ANbp generally reported more frequent restrictive eating behaviors than
      individuals with ANr. These differences were mostly accounted for by greater
      severity of eating psychopathology, indicating that the presence and frequency of
      restrictive eating behaviors in AN may be nonweight-based markers of severity.
      Binge eating frequency did not account for these findings. DISCUSSION: The
      present findings are especially interesting in light of the weight-based severity
      rating in the DSM-5.

PMID- 23868199
TI  - Molecular phylogeny of Neotropical bioluminescent beetles (Coleoptera:
      Elateroidea) in southern and central Brazil.
AB  - Bioluminescence in beetles is found mainly in the Elateroidea superfamily
      (Elateridae, Lampyridae and Phengodidae). The Neotropical region accounts for the
      richest diversity of bioluminescent species in the world with about 500 described
      species, most occurring in the Amazon, Atlantic rainforest and Cerrado (savanna)
      ecosystems in Brazil. The origin and evolution of bioluminescence, as well as the
      taxonomic status of several Neotropical taxa in these families remains unclear.
      In order to contribute to a better understanding of the phylogeny and evolution
      of bioluminescent Elateroidea we sequenced and analyzed sequences of
      mitochondrial NADH2 and the nuclear 28S genes and of the cloned luciferase
      sequences of Brazilian species belonging to the following genera: (Lampyridae)
      Macrolampis, Photuris, Amydetes, Bicellonycha, Aspisoma, Lucidota, Cratomorphus;
      (Elateridae) Conoderus, Pyrophorus, Hapsodrilus, Pyrearinus, Fulgeochlizus; and
      (Phengodidae) Pseudophengodes, Phrixothrix, Euryopa and Brasilocerus. Our study
      supports a closer phylogenetic relationship between Elateridae and Phengodidae as
      other molecular studies, in contrast with previous morphologic and molecular
      studies that clustered Lampyridae/Phengodidae. Molecular data also supported
      division of the Phengodinae subfamily into the tribes Phengodini and
      Mastinocerini. The position of the genus Amydetes supports the status of the
      Amydetinae as a subfamily. The genus Euryopa is included in the Mastinocerini
      tribe within the Phengodinae/Phengodidae.

PMID- 23868200
TI  - A case of the Starr-Edwards ball valve (Model 6120) in the mitral position for 45
      years.
AB  - A 59-year-old male who had undergone mitral valve replacement with the Starr
      Edwards ball valve Model 6120 (S-E ball valve) 45 years ago was admitted to our
      hospital for hemolytic anemia and heart failure. Echocardiography revealed that
      there was no valve dysfunction but paravalvular leakage between the annulus of P2
      and the sewing ring of the Starr-Edwards ball valve. He underwent mitral valve
      replacement. The S-E ball valve was successfully replaced with bileaflet
      mechanical valve. The explanted S-E ball valve was free from signs of structural
      valve degeneration. This case shows one of the longest durability of the S-E ball
      valve in mitral position in the world. 

PMID- 23868201
TI  - Endovenous radiofrequency ablation and combined foam sclerotherapy treatment of
      multiple refluxing perforator veins in a Klippel-Trenaunay syndrome patient.
AB  - We describe an unusual pattern of venous abnormality and the use of endovenous
      radiofrequency ablation, using the TRans-Luminal Occlusion of Perforator
      technique to treat multiple refluxing perforators in a 29-year-old patient with
      Klippel-Trenaunay syndrome. Klippel-Trenaunay syndrome is a rare congenital
      anomaly characterised by a triad of features including unilateral limb
      overgrowth, venous varicosities and capillary malformations of the affected limb.
      Ultrasound findings demonstrated 22 incompetent perforator veins in the lateral
      aspect of the patients left leg, communicating with a complex network of large
      calibre varicosities causing unilateral leg oedema and pain. Staged
      radiofrequency ablation procedures using the Olympus Celon RFITT (radiofrequency
      induced thermotherapy; please see Technical Note) device under local anaesthetic
      were performed. These procedures were followed with two sessions of foam
      sclerotherapy. This case report describes the efficacy of this treatment regime
      and this patient's significantly improved morbidity 18 months after initial
      treatment. 

PMID- 23868202
TI  - Effects of aural atresia on speech development and learning: retrospective
      analysis from a multidisciplinary craniofacial clinic.
AB  - IMPORTANCE Aural atresia (AA) is associated with maximal conductive hearing loss
      in affected ears, and children with bilateral AA require amplification. Some
      recent research has suggested an increased risk for speech and learning problems
      among children with unilateral sensorineural hearing loss. OBJECTIVE To
      investigate whether increased risk for speech and learning problems exists among
      children with AA. DESIGN Retrospective medical record review. SETTING
      Multidisciplinary craniofacial clinic. PARTICIPANTS Children with unilateral or
      bilateral AA. INTERVENTIONS Records review, including evaluations by
      audiologists, speech pathologists, and psychologists. MAIN OUTCOME MEASURES Rates
      of speech and/or language delay, prevalence of speech therapy and educational
      interventions, and parental report of psychosocial problems. RESULTS A total of
      74 patients were identified who met inclusion and exclusion criteria: 48 with
      right-sided AA, 19 with left-sided AA, and 7 with bilateral AA. Children with AA
      demonstrated high rates of speech therapy (86% among bilateral, 43% among
      unilateral). Reports of school problems were more common among children with
      right-sided AA (31%) than those with left-sided AA (11%) or bilateral AA (0%) (P
      = .06). Educational interventions were common in all groups (33% right, 21% left,
      43% bilateral). In the case of bilateral AA, all children who received additional
      interventions were enrolled in schools for the hearing impaired, without any
      identified learning deficiencies. CONCLUSIONS AND RELEVANCE Children with
      unilateral AA may be at greater risk of speech and learning difficulties than
      previously appreciated, similar to children with unilateral sensorineural hearing
      loss. Whether amplification may alleviate this risk is unclear and warrants
      further study.

PMID- 23868204
TI  - Simple modular systems for generation of droplets on demand.
AB  - This report provides practical guidelines for the use of inexpensive
      electromagnetic valves characterized by large dead volumes (tens to hundreds of
      MUL) for the generation of small (nL) droplets on demand in microfluidic chips.
      We analyze the role of the ratio of resistances and of the elastic capacitance of
      the fluidic connectors between the reservoir of the liquid, the valve and the
      microfluidic chip in the reliable and precise formation of micro droplets on
      demand. We also demonstrate and examine the use of conventional electromagnetic
      squeeze valves in the generation of small droplets on demand with a similar set
      of design rules. 

PMID- 23868206
TI  - Over-expression of regulator of G protein signaling 5 promotes tumor metastasis
      by inducing epithelial-mesenchymal transition in hepatocellular carcinoma cells.
AB  - BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the second leading
      cause of cancer-related deaths worldwide. The regulator of G-protein signaling 5
      (RGS5) has been reported to be highly expressed in some malignant tumors.
      However, its expression and role in HCC has not been reported. METHODS: The
      expression of RGS5 was examined in liver cancer tissues and cell lines by real
      time quantitative PCR. The cell migration and invasion was investigated by wound
      healing and transwell invasion assay. The epithelial-mesenchymal transition
      markers were detected by Western blotting or immunofluorescence. RESULTS: We
      observed that RGS5 is over-expressed in most of liver cancer tissue samples and
      cell lines compared with matched normal samples. Further analysis showed that the
      over-expression of RGS5 is associated with liver cancer recurrence, venous
      infiltration, and patients' poor survival. Next, we found that knockdown of RGS5
      significantly inhibits liver cancer cell migration and invasion in highly
      invasive liver cancer cells. Furthermore, we found that over-expression of RGS5
      induces epithelial-mesenchymal transition in epithelial liver cancer cells.
      CONCLUSIONS: These results indicate that over-expression of RGS5 promotes tumor
      metastasis by inducing epithelial-mesenchymal transition in HCC.

PMID- 23868207
TI  - Peptides as models for the structure and function of viral capsid proteins:
      Insights on dengue virus capsid.
AB  - The structural organization of viral particles is among the most astonishing
      examples of molecular self-assembly in nature, involving proteins, nucleic acids,
      and, sometimes, lipids. Proper assembly is essential to produce well structured
      infectious virions. A great variety of structural arrangements can be found in
      viral particles. Nucleocapsids, for instance, may display highly ordered
      geometric shapes or consist in macroscopically amorphous packs of the viral
      genome. Alphavirus and flavivirus are viral genera that exemplify these extreme
      cases, the former comprising viral particles structured with a T = 4 icosahedral
      symmetry, whereas flavivirus capsids have no regular geometry. Dengue virus is a
      member of flavivirus genus and is used in this article to illustrate how viral
      protein-derived peptides can be used advantageously over full-length proteins to
      unravel the foundations of viral supramolecular assemblies. Membrane- and viral
      RNA-binding data of capsid protein-derived dengue virus peptides are used to
      explain the amorphous organization of the viral capsid. Our results combine
      bioinformatic and spectroscopic approaches using two- or three-component peptide
      and/or nucleic acid and/or lipid systems.

PMID- 23868208
TI  - Functional and topological studies with Trp-containing analogs of the peptide
      StII(1-30) derived from the N-terminus of the pore forming toxin sticholysin II:
      contribution to understand its orientation in membrane.
AB  - Sticholysin II (St II) is the most potent cytolysin produced by the sea anemone
      Stichodactyla helianthus, exerting hemolytic activity via pore formation in
      membranes. The toxin's N-terminus contains an amphipathic alpha-helix that is
      very likely involved in pore formation. We have previously demonstrated that the
      synthetic peptide StII(1-30) encompassing the 1-30 segment of St II forms pores
      of similar radius to that of the protein (around 1 nm), being a good model of
      toxin functionality. Here we have studied the functional and conformational
      properties of fluorescent analogs of StII(1-30) in lipid membranes. The analogs
      were obtained by replacing Leu residues at positions 2, 12, 17, and 24 with the
      intrinsically fluorescent amino acid Trp (StII(1-30L2W), StII(1-30L12W), StII(1
      30L17W), or StII(1-30L24W), respectively). The exchange by Trp did not
      significantly modify the activity and conformation of the parent peptide. The
      blue-shift and intensity enhancement of fluorescence in the presence of membrane
      indicated that Trp at position 2 is more deeply buried in the hydrophobic region
      of the bilayer. These experiments, as well as assays with water-soluble or spin
      labeled lipid-soluble fluorescence quenchers suggest an orientation of StII(1-30)
      with its N-terminus oriented towards the hydrophobic core of the bilayer while
      the rest of the peptide is more exposed to the aqueous environment, as
      hypothesized for sticholysins.

PMID- 23868209
TI  - On the mechanism of degradation of oxytocin and its analogues in aqueous
      solution.
AB  - Oxytocin (OT) is a cyclic nonapeptide containing one internal disulfide bond
      between its Cys(1) and Cys(6) residues. Although OT is one of the most commonly
      used peptidic drugs, the mechanism of its degradation in aqueous solution and the
      identity of its degradants have not been fully elucidated. To investigate the
      pathways and products of OT degradation in slightly acidic to neutral solutions,
      we prepared the peptides: OT, [D-Cys(1)]OT, a series of N-alkylated OT analogues,
      [[(13)C3,(15) N]Cys(1)]OT, and OT where each sulfur atom was systematically
      replaced by either methylene, (34)S, or Se. The peptides were incubated at 40
      degrees C and the degradation products studied by HPLC, LCMS, and (13)C-NMR. Our
      findings suggest that the degradation begins with beta-elimination of the
      disulfide linkage to form a putative intermediate linear peptide containing an S
      thiocysteine (a persulfide) in position 6 and a dehydroalanine in position 1.
      This intermediate persulfide appears to donate a sulfur atom to an intact OT
      molecule to form OT trisulfide and higher monomeric polysulfides, while the
      dehydroalanine residue is hydrolyzed with loss of the N-terminal amino group to
      yield a linear N-pyruvoylated octapeptide containing a reduced Cys(6). Based on
      the MS and (13)C-NMR data of the products from degradation of
      [[(13)C3,(15)N]Cys(1)]OT, we postulate that the ultimate degradation products of
      OT are dimers composed of two pyruvoylated octapeptides held together by one
      disulfide bridge between the two Cys(6) residues and by one more, non-reducible,
      linkage resulting from an aldol-type condensation between the two N-terminal
      pyruvoyl groups.

PMID- 23868211
TI  - 23rd American Peptide Symposium.

PMID- 23868210
TI  - Peptide antagonists of the calcitonin gene-related peptide (CGRP) receptor with
      improved pharmacokinetics and pharmacodynamics.
AB  - Antagonism of the calcitonin gene-related peptide (CGRP) receptor may be a useful
      approach for migraine treatment. Selective PEGylated peptide antagonists to the
      CGRP receptor are described, derived from CGRP(8-37) with polymer derivatization
      at an engineered lysine-25 residue. Potent PEGylated peptides with improved
      pharmacokinetics were identified through peptide side-chain modification to
      mitigate metabolic liabilities. PEGylated Ac-Trp
      [Cit(11,18),hArg(24),Lys(25),Asp(31),Pro(34),1-Nal(35)]CGRP(8-37)-NH2, 9, elicits
      a dose-dependent reduction of intradermal CGRP-induced local blood flow in
      rodents with an ED50 of 0.52 mg kg(-1) without any overt adverse effects.

PMID- 23868212
TI  - Phytal: a candidate sex pheromone component of the moroccan locust dociostaurus
      maroccanus.
AB  - Outbreaks of locusts cause enormous economic losses to agriculture in many
      countries. To develop environmentally friendly strategies for their control, much
      research has been focused on the factors that influence locust biology,
      particularly infochemical-mediated interactions. We present herein the
      identification and synthesis of both Z and E isomers of phytal (3,7,11,15
      tetramethylhexadec-2-enal, 1), which are involved in chemical communication and
      behaviour of the Moroccan locust, Dociostaurus maroccanus, a serious agricultural
      pest. The compound was identified by comparison of its chromatographic and
      spectrometric features and microchemical reactions with those of a synthetic
      sample. The natural compound was shown to have the R,R configuration by chiral
      HPLC analysis, and its structure is unique as an insect pheromone component. Both
      isomers of phytal are produced by sexually mature adult males and elicit
      electroantennographic responses in antennae of both sexes. In two-choice
      olfactometer bioassays, males and females significantly preferred the stream
      enriched with racemic phytal to the control. In contrast, hydrogenated phytal was
      behaviourally inert. Both isomers of phytal are specific to D. maroccanus as they
      are absent in the closely related, habitat-sharing species Dociostaurus jagoi and
      Calliptamus wattenwylianus. Legs and wings are the main release sites of the
      compound: approximately 90 % of that emitted by living individuals. In
      biosynthetic studies, phytal appears to proceed from oxidation of phytol (2)
      after injection of deuterated phytol into the abdomen of the insect or after
      administration in the diet. Our results demonstrate that phytal is a candidate
      sex pheromone component of the Moroccan locust; it is produced by mature males,
      and might be eavesdropped upon by conspecific males. 

PMID- 23868213
TI  - The cytotoxic and proapoptotic activities of hypnophilin are associated with
      calcium signaling in UACC-62 cells.
AB  - Hypnophilin (HNP) is a sesquiterpene that is isolated from Lentinus cf. strigosus
      and has cytotoxic activities. Here, we studied the calcium signaling and
      cytotoxic effects of HNP in UACC-62 cells, a human skin melanoma cell line. HNP
      was able to increase the intracellular calcium concentration in UACC-62 cells,
      which was blocked in cells stimulated in Ca(2+) -free media. HNP treatment with
      BAPTA-AM, an intracellular Ca(2+) chelator, caused an increase in calcium
      signals. HNP showed cytotoxicity against UACC-62 cells in which it induced DNA
      fragmentation and morphological alterations, including changes in the nuclear
      chromatin profile and increased cytoplasmatic vacuolization, but it had no effect
      on the plasma membrane integrity. These data suggest that cytotoxicity in UACC-62
      cells, after treatment with HNP, is associated with Ca(2+) influx. Together,
      these findings suggest that HNP is a relevant tool for the further investigation
      of new anticancer approaches.

PMID- 23868214
TI  - A kernel regression approach to gene-gene interaction detection for case-control
      studies.
AB  - Gene-gene interactions are increasingly being addressed as a potentially
      important contributor to the variability of complex traits. Consequently,
      attentions have moved beyond single locus analysis of association to more complex
      genetic models. Although several single-marker approaches toward interaction
      analysis have been developed, such methods suffer from very high testing
      dimensionality and do not take advantage of existing information, notably the
      definition of genes as functional units. Here, we propose a comprehensive family
      of gene-level score tests for identifying genetic elements of disease risk, in
      particular pairwise gene-gene interactions. Using kernel machine methods, we
      devise score-based variance component tests under a generalized linear mixed
      model framework. We conducted simulations based upon coalescent genetic models to
      evaluate the performance of our approach under a variety of disease models. These
      simulations indicate that our methods are generally higher powered than
      alternative gene-level approaches and at worst competitive with exhaustive SNP
      level (where SNP is single-nucleotide polymorphism) analyses. Furthermore, we
      observe that simulated epistatic effects resulted in significant marginal testing
      results for the involved genes regardless of whether or not true main effects
      were present. We detail the benefits of our methods and discuss potential genome
      wide analysis strategies for gene-gene interaction analysis in a case-control
      study design. 

PMID- 23868215
TI  - Safety and efficacy of percutaneous femoral artery access followed by Mynx
      closure in cerebral neurovascular procedures: a single center analysis.
AB  - BACKGROUND AND PURPOSE: Percutaneous transfemoral arterial procedures rely on a
      variety of vascular closure methods. We studied closure success and complications
      after using the Mynx vascular closure device in cerebral neurovascular
      procedures. METHODS: We prospectively analyzed patients undergoing diagnostic
      cerebral angiogram or neurointervention with arteriotomy closure using the Mynx
      device. Patient demographics and procedural factors were recorded. Statistical
      analyses compared groups and identified predictors of device failure and
      complication. RESULTS: A total of 766 patients, 59% women, mean age 55.5 years
      (SD 14.2), mean body mass index (BMI) 29.1 kg/m(2) (SD 7.4), underwent 937
      neurovascular procedures in a 10 month period. Device success was achieved in 92%
      of patients; lower BMI, higher number of antithrombotic medications, larger
      sheath size, and performance of a neurointerventional procedure predicted Mynx
      failure. Complications occurred in 2.45% of procedures, with older age, lower
      BMI, higher number of antithrombotic medicines used, higher international
      normalized ratio, lower platelet count, and Mynx device failure conferring an
      increased risk of complication. CONCLUSIONS: The Mynx device is safe and
      effective for cerebral neurovascular procedures. However, specific patient
      populations may warrant particular attention and thorough consideration of risks
      and benefits prior to employing the Mynx device for femoral arteriotomy closure.

PMID- 23868216
TI  - Aspiration thrombectomy in concert with stent thrombectomy.
AB  - In the SWIFT and TREVO 2 trials, aspiration thrombectomy was not able to be
      performed. Outside these studies, in post-market application, the interventionist
      can use aspiration thrombectomy in addition to stent device thrombectomy. This
      technique is described in detail in the present report. Combined
      aspiration/stentriever thrombectomy may improve recanalization efforts, simplify
      a second thrombectomy attempt if necessary and may limit distal embolization. 

PMID- 23868217
TI  - B cell tolerance: STALling B cell responses.

PMID- 23868218
TI  - Immunodeficiency: magnesium regulates antiviral immunity.

PMID- 23868219
TI  - T cells: maintaining T cell homeostasis.

PMID- 23868220
TI  - Influenza virus: lethal weapons.

PMID- 23868221
TI  - A large cohort study of nonsteroidal anti-inflammatory drugs and renal cell
      carcinoma incidence in the National Institutes of Health-AARP Diet and Health
      Study.
AB  - AIM: Existing epidemiologic evidence for the association between nonsteroidal
      anti-inflammatory drugs (NSAIDs) and renal cell carcinoma (RCC) risk is
      inconsistent. METHODS: We investigated the association between the use of aspirin
      and nonaspirin NSAIDs and RCC risk in the National Institutes of Health-American
      Association of Retired Persons (AARP) Diet and Health Study, for which 298,468
      AARP members free of cancer, aged 50-71 years, completed a survey on use of
      NSAIDs (1996-1997). Multivariate Cox proportional hazards models were used to
      estimate the hazard ratio (HR). RESULTS: The state cancer registry and mortality
      index linkage identified 1,084 incident RCC cases through 31 December 2006. No
      statistically significant associations between the use of aspirin or nonaspirin
      NSAIDs and RCC risk were found. Compared to nonuse of any NSAIDs, the
      multivariate-adjusted HRs were 0.95 (95 % CI 0.75-1.21) and 0.93 (95 % CI 0.68
      1.26) for monthly use of aspirin and nonaspirin NSAIDs, respectively, 0.92 (95 %
      CI: 0.69-1.23) and 1.11 (95 % CI: 0.76-1.62) for weekly use, 0.87 (95 % CI: 0.69
      1.11) and 1.06 (95 % CI: 0.75-1.48) for daily use; and 0.95 (95 % CI 0.78-1.14)
      for the use of both aspirin and nonaspirin NSAIDs. We found some suggestions of
      an increased risk of RCC associated with frequent NSAID use among participants
      who were <63 years and a reduced risk associated with aspirin use among those
      >=63 years. No significant associations were found in other stratified analyses
      by gender, BMI, smoking, history of diabetes, or history of hypertension.
      CONCLUSION: RCC risk was not significantly associated with NSAID use overall. The
      difference in association by age needs to be explored further.

PMID- 23868222
TI  - Expert's comment concerning Grand Rounds case entitled "Minimal access bilateral
      transforaminal lumbar interbody fusion for high-grade isthmic spondylolisthesis"
      (by Nasir A. Quraishi and Y. Raja Rampersaud; doi:10.1007/s00586-012-2623-2).
AB  - This Expert's Comment discusses the Grand Rounds Case entitled "Minimal Access
      Bilateral Transforaminal Lumbar Interbody Fusion for High-Grade Isthmic
      Spondylolisthesis" by Nasir A Quraishi and Raja Y Rampersaud. It puts a
      technically elegant surgical method for minimally invasive reduction and
      arthrodesis of isthmic spondylolistheses into the context of short and long term
      outcomes and questions the motivations for performing such minimally invasive
      procedures in the absence of any proven mid or long term advantages over more
      traditional techniques. In addition, the use of BMP in spinal arthrodesis is
      discussed on the background of recently published IPD metaanalyses from the
      Infuse spinal FDA trials.

PMID- 23868224
TI  - Don't market stem-cell products ahead of proof.

PMID- 23868236
TI  - Asteroid plan looks rocky.

PMID- 23868223
TI  - Parameters influencing the outcome after total disc replacement at the
      lumbosacral junction. Part 1: misalignment of the vertebrae adjacent to a total
      disc replacement affects the facet joint and facet capsule forces in a
      probabilistic finite element analysis.
AB  - PURPOSE: After total disc replacement with a ball-and-socket joint, reduced range
      of motion and progression of facet joint degeneration at the index level have
      been described. The aim of the study was to test the hypothesis that misalignment
      of the vertebrae adjacent to the implant reduces range of motion and increases
      facet joint or capsule tensile forces. METHODS: A probabilistic finite element
      analysis was performed using a lumbosacral spine model with an artificial disc at
      level L5/S1. Misalignment of the L5 vertebra, the gap size of the facet joints,
      the transection of the posterior longitudinal ligament, and the spinal shape were
      varied. The model was loaded with pure moments. RESULTS: Misalignment of the L5
      vertebra reduced the range of motion up to 2 degrees . A 2-mm displacement of the
      L5 vertebra in the anterior direction already led to facet joint forces of
      approximately 240 N. Extension, lateral bending, and axial rotation caused
      maximum facet joint forces between 280 and 380 N, while flexion caused maximum
      forces of approximately 200 N. A 2-mm displacement in the posterior direction led
      to capsule forces of approximately 80 N. Additional moments increased the maximum
      facet capsule forces to values between 120 and 230 N. CONCLUSIONS: Misalignment
      of the vertebrae adjacent to an artificial disc strongly increases facet joint or
      capsule forces. It might, therefore, be an important reason for unsatisfactory
      clinical results. In an associated clinical study (Part 2), these findings are
      validated.

PMID- 23868237
TI  - Hunt for mystery GM wheat hots up.

PMID- 23868238
TI  - NIH gambles on recycled drugs.

PMID- 23868239
TI  - Rinderpest research restarts.

PMID- 23868240
TI  - Fukushima offers real-time ecolab.

PMID- 23868241
TI  - Lasers boost space communications.

PMID- 23868243
TI  - Education online: the virtual lab.

PMID- 23868244
TI  - Neuroscience: solving the brain.

PMID- 23868245
TI  - Digital learning: look, then leap.

PMID- 23868246
TI  - Education: online on-ramps.

PMID- 23868250
TI  - Russian science: academy reform needs a reality check.

PMID- 23868251
TI  - Analysis: don't do big-data science backwards.

PMID- 23868252
TI  - Science and the public: promotional tactics corrupt research.

PMID- 23868253
TI  - Reproducibility: two more red flags for suspect work.

PMID- 23868254
TI  - Quantum physics: Andreev states taken to the next level.

PMID- 23868256
TI  - Particle physics: let it B.

PMID- 23868257
TI  - Cancer: calculated treatment.

PMID- 23868258
TI  - Ultrasensitive fluorescent proteins for imaging neuronal activity.
AB  - Fluorescent calcium sensors are widely used to image neural activity. Using
      structure-based mutagenesis and neuron-based screening, we developed a family of
      ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors
      in cultured neurons and in zebrafish, flies and mice in vivo. In layer 2/3
      pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single
      action potentials in neuronal somata and orientation-tuned synaptic calcium
      transients in individual dendritic spines. The orientation tuning of structurally
      persistent spines was largely stable over timescales of weeks. Orientation tuning
      averaged across spine populations predicted the tuning of their parent cell.
      Although the somata of GABAergic neurons showed little orientation tuning, their
      dendrites included highly tuned dendritic segments (5-40-um long). GCaMP6 sensors
      thus provide new windows into the organization and dynamics of neural circuits
      over multiple spatial and temporal scales. 

PMID- 23868259
TI  - Myomaker is a membrane activator of myoblast fusion and muscle formation.
AB  - Fusion of myoblasts is essential for the formation of multi-nucleated muscle
      fibres. However, the identity of muscle-specific proteins that directly govern
      this fusion process in mammals has remained elusive. Here we identify a muscle
      specific membrane protein, named myomaker, that controls myoblast fusion.
      Myomaker is expressed on the cell surface of myoblasts during fusion and is
      downregulated thereafter. Overexpression of myomaker in myoblasts markedly
      enhances fusion, and genetic disruption of myomaker in mice causes perinatal
      death due to an absence of multi-nucleated muscle fibres. Remarkably, forced
      expression of myomaker in fibroblasts promotes fusion with myoblasts,
      demonstrating the direct participation of this protein in the fusion process.
      Pharmacological perturbation of the actin cytoskeleton abolishes the activity of
      myomaker, consistent with previous studies implicating actin dynamics in myoblast
      fusion. These findings reveal a long-sought myogenic fusion protein that controls
      mammalian myoblast fusion and provide new insights into the molecular
      underpinnings of muscle formation. 

PMID- 23868261
TI  - Exciting Andreev pairs in a superconducting atomic contact.
AB  - The Josephson effect describes the flow of supercurrent in a weak link-such as a
      tunnel junction, nanowire or molecule-between two superconductors. It is the
      basis for a variety of circuits and devices, with applications ranging from
      medicine to quantum information. Experiments using Josephson circuits that behave
      like artificial atoms are now revolutionizing the way we probe and exploit the
      laws of quantum physics. Microscopically, the supercurrent is carried by Andreev
      pair states, which are localized at the weak link. These states come in doublets
      and have energies inside the superconducting gap. Existing Josephson circuits are
      based on properties of just the ground state of each doublet, and so far the
      excited states have not been directly detected. Here we establish their existence
      through spectroscopic measurements of superconducting atomic contacts. The
      spectra, which depend on the atomic configuration and on the phase difference
      between the superconductors, are in complete agreement with theory. Andreev
      doublets could be exploited to encode information in novel types of
      superconducting qubits. 

PMID- 23868260
TI  - LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling.
AB  - Aberrant neovascularization contributes to diseases such as cancer, blindness and
      atherosclerosis, and is the consequence of inappropriate angiogenic signalling.
      Although many regulators of pathogenic angiogenesis have been identified, our
      understanding of this process is incomplete. Here we explore the transcriptome of
      retinal microvessels isolated from mouse models of retinal disease that exhibit
      vascular pathology, and uncover an upregulated gene, leucine-rich alpha-2
      glycoprotein 1 (Lrg1), of previously unknown function. We show that in the
      presence of transforming growth factor-beta1 (TGF-beta1), LRG1 is mitogenic to
      endothelial cells and promotes angiogenesis. Mice lacking Lrg1 develop a mild
      retinal vascular phenotype but exhibit a significant reduction in pathological
      ocular angiogenesis. LRG1 binds directly to the TGF-beta accessory receptor
      endoglin, which, in the presence of TGF-beta1, results in promotion of the pro
      angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this
      switch and attenuates angiogenesis. These studies reveal a new regulator of
      angiogenesis that mediates its effect by modulating TGF-beta signalling. 

PMID- 23868263
TI  - Ratios of S, Se and Te in the silicate Earth require a volatile-rich late veneer.
AB  - The excess of highly siderophile (iron-loving) elements (HSEs) and the chondritic
      ratios of most HSEs in the bulk silicate Earth (BSE) may reflect the accretion of
      a chondritic 'late veneer' of about 0.5 per cent of Earth's mass after core
      formation. The amount of volatiles contained in the late veneer is a key
      constraint on the budget and the origin of the volatiles in Earth. At high
      pressures and temperatures, the moderately volatile chalcogen elements sulphur
      (S), selenium (Se) and tellurium (Te) are moderately to highly siderophile; thus,
      if depleted by core formation their mantle abundances should reflect the volatile
      composition of the late veneer. Here we report ratios and abundances of S, Se and
      Te in the mantle determined from new isotope dilution data for post-Archaean
      mantle peridotites. The mean S/Se and Se/Te ratios of mantle lherzolites overlap
      with CI (Ivuna-type) carbonaceous chondrite values. The Se/Te ratios of ordinary
      and enstatite chondrites are significantly different. The chalcogen/HSE ratio of
      the BSE is similar to that of CM (Mighei-type) carbonaceous chondrites,
      consistent with the view that the HSE signature of the BSE reflects a
      predominance of slightly volatile-depleted, carbonaceous-chondrite-like material,
      possibly with a minor proportion of non-chondritic material. Depending on the
      estimates for the abundances of water and carbon in the BSE, the late veneer may
      have supplied 20 to 100 per cent of the budget of hydrogen and carbon in the BSE.

PMID- 23868262
TI  - Elucidation of the Fe(IV)=O intermediate in the catalytic cycle of the halogenase
      SyrB2.
AB  - Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative
      reactions, including halogenation, hydroxylation, ring closure, desaturation and
      aromatic ring cleavage reactions. They are involved in a number of biological
      processes, including phenylalanine metabolism, the production of
      neurotransmitters, the hypoxic response and the biosynthesis of secondary
      metabolites. The reactive intermediate in the catalytic cycles of these enzymes
      is a high-spin S = 2 Fe(IV)=O species, which has been trapped for a number of
      NHFe enzymes, including the halogenase SyrB2 (syringomycin biosynthesis enzyme
      2). Computational studies aimed at understanding the reactivity of this Fe(IV)=O
      intermediate are limited in applicability owing to the paucity of experimental
      knowledge about its geometric and electronic structure. Synchrotron-based nuclear
      resonance vibrational spectroscopy (NRVS) is a sensitive and effective method
      that defines the dependence of the vibrational modes involving Fe on the nature
      of the Fe(IV)=O active site. Here we present NRVS structural characterization of
      the reactive Fe(IV)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2
      from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts
      via an initial hydrogen-atom abstraction step, performing subsequent halogenation
      of the native substrate or hydroxylation of non-native substrates. A correlation
      of the experimental NRVS data to electronic structure calculations indicates that
      the substrate directs the orientation of the Fe(IV)=O intermediate, presenting
      specific frontier molecular orbitals that can activate either selective
      halogenation or hydroxylation.

PMID- 23868265
TI  - Surgical decompression for space-occupying cerebral infarction: outcomes at 3
      years in the randomized HAMLET trial.
AB  - BACKGROUND AND PURPOSE: We assessed whether the effects of surgical decompression
      for space-occupying hemispheric infarction, observed at 1 year, are sustained at
      3 years. METHODS: Patients with space-occupying hemispheric infarction, who were
      enrolled in the Hemicraniectomy After Middle cerebral artery infarction with Life
      threatening Edema Trial within 4 days after stroke onset, were followed up at 3
      years. Outcome measures included functional outcome (modified Rankin Scale),
      death, quality of life, and place of residence. Poor functional outcome was
      defined as modified Rankin Scale >3. RESULTS: Of 64 included patients, 32 were
      randomized to decompressive surgery and 32 to best medical treatment. Just as at
      1 year, surgery had no effect on the risk of poor functional outcome at 3 years
      (absolute risk reduction, 1%; 95% confidence interval, -21 to 22), but it reduced
      case fatality (absolute risk reduction, 37%; 95% confidence interval, 14-60).
      Sixteen surgically treated patients and 8 controls lived at home (absolute risk
      reduction, 27%; 95% confidence interval, 4-50). Quality of life improved between
      1 and 3 years in patients treated with surgery. CONCLUSIONS: In patients with
      space-occupying hemispheric infarction, the effects of decompressive surgery on
      case fatality and functional outcome observed at 1 year are sustained at 3 years.
      CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique
      identifier: ISRCTN94237756.

PMID- 23868266
TI  - Retinal microvascular changes and risk of stroke: the Singapore Malay Eye Study.
AB  - BACKGROUND AND PURPOSE: To examine the relationship between retinal microvascular
      measures and incident stroke in an Asian Malay population. METHODS: We conducted
      a prospective, population-based cohort study of Asian Malay persons 40 to 80
      years at baseline. Retinal microvascular signs were assessed from baseline
      retinal photographs including quantitative retinal microvascular parameters
      (caliber, branching angle, tortuosity, and fractal dimension) and qualitative
      retinopathy signs. Incident stroke cases were identified during the follow-up
      period. Cox proportional-hazards regression and incremental usefulness analysis
      (calibration, discrimination, and reclassification) were performed. RESULTS: A
      total of 3189 participants were free of prevalent stroke at baseline. During the
      follow-up (median, 4.41 years), 51 (1.93%) participants had an incident stroke
      event. In Cox proportional-hazards models adjusting for established stroke
      predictors (age, sex, systolic blood pressure, total cholesterol, low-density
      lipoprotein cholesterol, smoking, glycosylated hemoglobin, and antihypertensive
      medication), retinopathy (hazard ratio, 1.94; 95% confidence interval, 1.01-3.72)
      and larger retinal venular caliber (hazard ratio, 3.28; 95% confidence interval,
      1.30-8.26, comparing fourth versus first quartiles) were associated with risk of
      stroke. Compared with the model with only established risk factors, the addition
      of retinal measures improved the prediction of stroke (C-Statistic 0.826 versus
      0.792; P=0.017) and correctly reclassified 5.9% of participants with incident
      stroke and 3.4% of participants with no incident stroke. CONCLUSIONS: Retinal
      microvascular changes are related to an increased risk of stroke in Asian Malay,
      consistent with data from white populations. Retinal imaging improves the
      discrimination and stratification of stroke risk beyond that of established risk
      factors by a significant but small margin.

PMID- 23868267
TI  - Insular strokes cause no vestibular deficits.
AB  - BACKGROUND AND PURPOSE: In previous imaging studies, the posterior insular cortex
      (IC) was identified as an essential part for vestibular otolith perception and
      considered as a core region of a human vestibular cortical network. However, it
      is still unknown whether lesions exclusively restricted to the posterior IC
      suffice to provoke signs of vestibular otolith dysfunction. Thus, present data
      aimed to test whether patients with lesions restricted to the IC showed
      vestibular otolith dysfunction. METHODS: We studied 10 acute unilateral stroke
      patients with lesions restricted to the IC which were tested for signs of
      vestibular otolith dysfunction, such as tilts of subjective visual vertical, out
      of 475 stroke patients. RESULTS: None of the patients was with stroke exclusively
      affecting the IC-specified vertigo as a symptom. In addition, neither showed a
      deficit in the perception of verticality (subjective visual vertical tilts) nor
      showed any further vestibular otolith deficits, such as ocular torsion or skew
      deviation. CONCLUSIONS: It seems that lesions of the posterior IC might have to
      be combined with lesions of adjacent regions of the cortical and subcortical
      vestibular network to cause vestibular otolith deficits.

PMID- 23868268
TI  - Inhibition of calcium/calmodulin-dependent protein kinase kinase beta and
      calcium/calmodulin-dependent protein kinase IV is detrimental in cerebral
      ischemia.
AB  - BACKGROUND AND PURPOSE: Elevation of intracellular calcium was traditionally
      thought to be detrimental in stroke pathology. However, clinical trials testing
      treatments that block calcium signaling have failed to improve outcomes in
      ischemic stroke. Emerging data suggest that calcium may also trigger endogenous
      protective pathways after stroke. Calcium/calmodulin-dependent protein kinase
      kinase (CaMKK) is a major kinase activated by rising intracellular calcium.
      Compelling evidence has suggested that CaMKK and its downstream kinase CaMK IV
      are critical in neuronal survival when cells are under ischemic stress. We
      examined the functional role of CaMKK/CaMK IV signaling in stroke. METHODS: We
      used a middle cerebral artery occlusion model in mice. RESULTS: Our data
      demonstrated that pharmacological and genetic inhibition of CaMKK aggravated
      stroke injury. Additionally, deletion of CaMKK beta, one of the 2 CaMKK isoforms,
      reduced CaMK IV activation, and CaMK IV deletion in mice worsened stroke outcome.
      Finally, CaMKK beta or CaMK IV knockout mice had exacerbated blood-brain barrier
      disruption evidenced by increased hemorrhagic transformation and activation of
      matrix metalloproteinase. We observed transcriptional inactivation including
      reduced levels of histone deacetylase 4 phosphorylation in mice with CaMKK beta
      or CaMK IV deletion after stroke. CONCLUSIONS: Our data have established that the
      CaMKK/CaMK IV pathway is a key endogenous protective mechanism in ischemia. Our
      results suggest that this pathway serves as an important regulator of blood-brain
      barrier integrity and transcriptional activation of neuroprotective molecules in
      stroke.

PMID- 23868269
TI  - Arterial spin-labeled perfusion imaging to predict mismatch in acute ischemic
      stroke.
AB  - BACKGROUND AND PURPOSE: We assigned a threshold to arterial spin-labeling (ASL)
      perfusion-weighted images (PWI) from patients with acute ischemic stroke and
      compared them with dynamic susceptibility contrast perfusion images to examine
      whether mismatch can be determined. METHODS: Pseudocontinuous ASL was combined
      with dynamic susceptibility contrast PWI in 23 patients with acute ischemic
      stroke. Scans were obtained within 24 hours of symptom onset. PWI volumes were
      defined by ASL cerebral blood flow (<15, <20, and <25 mL/100 g per minute) and
      dynamic susceptibility contrast-mean transit time (MTT) thresholds (>10 s) that
      show a strong association with cerebral blood flow <20 mL/100 g per minute in
      Xenon CT studies. Agreement between the ASL-diffusion-weighted imaging and MTT
      diffusion-weighted imaging mismatch and the correlation between penumbra salvage
      and infarct growth, defined as the difference between the baseline PWI and the
      baseline diffusion-weighted imaging lesion, respectively, and the final infarct
      volume were assessed. RESULTS: The lesion volumes defined by MTT>10 s and ASL<20
      mL/100 g per minute showed an excellent correlation. There was 100% agreement on
      the mismatch status between MTT>10 s and ASL<20 mL/100 g per minute. The
      correlation between infarct growth and penumbra salvage volume was significantly
      better for PWI lesions defined by ASL<20 mL/100 g per minute and MTT>10 s.
      CONCLUSIONS: In acute ischemic stroke, PWI lesions based on ASL threshold of <20
      mL/100 g per minute can provide a reliable estimate of mismatch in correspondence
      at MTT threshold of >10 s.

PMID- 23868270
TI  - Potentially large yet uncertain benefits: a meta-analysis of patent foramen ovale
      closure trials.

PMID- 23868271
TI  - Physical activity frequency and risk of incident stroke in a national US study of
      blacks and whites.
AB  - BACKGROUND AND PURPOSE: Regular physical activity (PA) is an important
      recommendation for stroke prevention. We compared the associations of self
      reported PA with incident stroke in the Reasons for Geographic and Racial
      Differences in Stroke (REGARDS) study. METHODS: REGARDS recruited 30 239 US
      blacks (42%) and whites, aged >=45 years with follow-up every 6 months for stroke
      events. Excluding those with prior stroke, analysis involved 27 348 participants
      who reported their frequency of moderate to vigorous intensity PA at baseline
      according to 3 categories: none (physical inactivity), 1 to 3*, and >=4* per
      week. Stroke and transient ischemic attack cases were identified during an
      average of 5.7 years of follow-up. Cox proportional hazards models were
      constructed to examine whether self-reported PA was associated with risk of
      incident stroke. RESULTS: Physical inactivity was reported by 33% of participants
      and was associated with a hazard ratio of 1.20 (95% confidence intervals, 1.02
      1.42; P=0.035). Adjustment for demographic and socioeconomic factors did not
      affect hazard ratio, but further adjustment for traditional stroke risk factors
      (diabetes mellitus, hypertension, body mass index, alcohol use, and smoking)
      partially attenuated this risk (hazard ratio, 1.14 [0.95-1.37]; P=0.17). There
      was no significant association between PA frequency and risk of stroke by sex
      groups, although there was a trend toward increased risk for men reporting PA 0
      to 3* a week compared with >=4* a week. CONCLUSIONS: Self-reported low PA
      frequency is associated with increased risk of incident stroke. Any effect of PA
      is likely to be mediated through reducing traditional risk factors.

PMID- 23868272
TI  - Systolic blood pressure during acute stroke is associated with functional status
      and long-term mortality in the elderly.
AB  - BACKGROUND AND PURPOSE: The prognostic value of blood pressure (BP) levels during
      acute stroke has not been adequately studied. Most studies do not use continuous
      BP measurements, and patients are followed only for a short period. We designed a
      study to assess, with 24-hour BP monitoring (24H BPM), the impact of BP levels
      during the first day of stroke, on the short-term functional status and long-term
      mortality in elderly patients. METHODS: We studied 177 patients with acute stroke
      (89 men), mean age 84+/-6 years. BP was measured on admission and 24H BPM was
      recorded within 24 hours of admission. After 7 days, patients were assessed for
      functional status according to the modified Rankin Scale and were subsequently
      followed up for mortality <=5 years (mean, 2.07+/-1.48). RESULTS: After 7 days,
      functional status improved and modified Rankin Scale decreased from 4.2 to 3.7.
      Follow-up analysis disclosed that 71 patients (27 men and 44 women) had died.
      Mortality rate was higher in women (50% versus 30%; P<0.01) and in patients with
      a history of congestive heart failure. Only average systolic BP, recorded by 24H
      BPM, predicted short-term functional status and long-term mortality. Cox
      proportional hazards model analysis demonstrated that age, sex, congestive heart
      failure, and average systolic BP >160 mm Hg, recorded by 24H BPM, were associated
      with increased mortality. CONCLUSIONS: High systolic BP recorded by 24H BPM on
      the first day of stroke was found to be associated with unfavorable short-term
      functional status and long-term mortality in elderly patients.

PMID- 23868273
TI  - Intravenous minocycline in acute stroke: a randomized, controlled pilot study and
      meta-analysis.
AB  - BACKGROUND AND PURPOSE: Minocycline, in animal models and 2 small randomized
      controlled human trials, is a promising neuroprotective agent in acute stroke. We
      analyzed the efficacy and safety of intravenous minocycline in acute ischemic and
      hemorrhagic stroke. METHODS: A multicenter prospective randomized open-label
      blinded end point evaluation pilot study of minocycline 100 mg administered
      intravenously, commenced within 24 hours of onset of stroke, and continued 12
      hourly for a total of 5 doses, versus no minocycline. All participants received
      routine stroke care. Primary end point was survival free of handicap (modified
      Rankin Scale, <=2) at day 90. RESULTS: Ninety-five participants were randomized;
      47 to minocycline and 48 to no minocycline. In the intention-to-treat population,
      29 of 47 (65.9%) allocated minocycline survived free of handicap compared with 33
      of 48 (70.2%) allocated no minocycline (rate ratio, 0.94; 95% confidence
      interval, 0.71-1.25 and odds ratio, 0.73; 95% CI, 0.31-1.71). A meta-analysis of
      the 3 human trials suggests minocycline may increase the odds of handicap-free
      survival by 3-fold (odds ratio, 2.99; 95% CI, 1.74-5.16) but there was
      substantial heterogeneity among the trials. CONCLUSIONS: In this pilot study of a
      small sample of acute stroke patients, intravenous minocycline was safe but not
      efficacious. The study was not powered to identify reliably or exclude a modest
      but clinically important treatment effect of minocycline. Larger trials would
      improve the precision of the estimates of any treatment effect of minocycline.
      CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au. Unique identifier:
      ACTRN12612000237886.

PMID- 23868274
TI  - Natural history of unruptured intracranial aneurysms: a long-term follow-up
      study.
AB  - BACKGROUND AND PURPOSE: Unruptured intracranial aneurysms are increasingly being
      detected and are a notable healthcare burden. We investigated the long-term
      natural history of unruptured intracranial aneurysms and risk factors predictive
      of subsequent rupture. METHODS: A total of 142 patients with 181 unruptured
      intracranial aneurysms diagnosed between 1956 and 1978, when these were not
      treated, were followed up until death or subarachnoid hemorrhage, or until 2011
      to 2012. Annual and cumulative incidences of aneurysm rupture and risk factors
      for rupture were studied using Kaplan-Meier survival analysis and Cox
      proportional hazards regression models. RESULTS: The median follow-up time was
      21.0 (range, 0.8-52.3) years. During 3064 person-years, there were 34 first
      episodes of aneurysm rupture, giving an average annual incidence of 1.1%.
      Eighteen patients died on account of an initial or recurrent aneurysm rupture.
      The cumulative rate of bleeding was 10.5% (95% confidence interval [CI], 5.2
      15.8) at 10 years, 23.0% (95% CI, 15.4-30.6) at 20 years, and 30.1% (95% CI, 21.3
      38.9) at 30 years. None of the index aneurysms bled after a follow-up of 25
      years. Cigarette smoking (adjusted hazard ratio, 2.44; 95% CI, 1.02-5.88),
      location of the aneurysm in the anterior communicating artery (adjusted hazard
      ratio, 3.73; 95% CI, 1.23-11.36), patient age inversely (0.96 per year, 95% CI,
      0.92-1.00) and aneurysm diameter >=7 mm (adjusted hazard ratio, 2.60; 95% CI,
      1.13-5.98) independently predicted subsequent aneurysm rupture, as did alcohol
      consumption (1.27 per 100 g/week; 95% CI, 1.05-1.53; P<0.05), but only in
      univariable analysis. CONCLUSIONS: Cigarette smoking, patient age inversely, and
      the size and location of the unruptured intracranial aneurysm seem to be risk
      factors for aneurysm rupture. The risk of bleeding decreases with a very long
      term follow-up.

PMID- 23868275
TI  - In-hospital risk prediction for post-stroke depression: development and
      validation of the Post-stroke Depression Prediction Scale.
AB  - BACKGROUND AND PURPOSE: The timely detection of post-stroke depression is
      complicated by a decreasing length of hospital stay. Therefore, the Post-stroke
      Depression Prediction Scale was developed and validated. The Post-stroke
      Depression Prediction Scale is a clinical prediction model for the early
      identification of stroke patients at increased risk for post-stroke depression.
      METHODS: The study included 410 consecutive stroke patients who were able to
      communicate adequately. Predictors were collected within the first week after
      stroke. Between 6 to 8 weeks after stroke, major depressive disorder was
      diagnosed using the Composite International Diagnostic Interview. Multivariable
      logistic regression models were fitted. A bootstrap-backward selection process
      resulted in a reduced model. Performance of the model was expressed by
      discrimination, calibration, and accuracy. RESULTS: The model included a medical
      history of depression or other psychiatric disorders, hypertension, angina
      pectoris, and the Barthel Index item dressing. The model had acceptable
      discrimination, based on an area under the receiver operating characteristic
      curve of 0.78 (0.72-0.85), and calibration (P value of the U-statistic, 0.96).
      Transforming the model to an easy-to-use risk-assessment table, the lowest risk
      category (sum score, <-10) showed a 2% risk of depression, which increased to 82%
      in the highest category (sum score, >21). CONCLUSIONS: The clinical prediction
      model enables clinicians to estimate the degree of the depression risk for an
      individual patient within the first week after stroke.

PMID- 23868276
TI  - Ideal cardiovascular health metrics and the risks of ischemic and intracerebral
      hemorrhagic stroke.
AB  - BACKGROUND AND PURPOSE: Previous studies showed an inverse association between
      ideal cardiovascular health (CVH) metrics and the total risk of cardiovascular
      diseases and stroke. This study aimed to investigate the relationship between
      ideal CVH metrics and the risks of ischemic and hemorrhagic stroke, respectively.
      METHODS: We collected information on the 7 ideal CVH metrics (including smoking
      status, body mass index, dietary intake, physical activity, blood pressure, total
      cholesterol, and fasting blood glucose) among 91 698 participants from the
      Kailuan study, China (72 826 men and 18 872 women between the ages of 18 and 98
      years), free of myocardial infarction and stroke at baseline (2006-2007). Cox
      proportional hazards models were used to estimate stroke risk. RESULTS: During
      the 4-year follow-up, we identified 1486 incident stroke events (1057 ischemic,
      386 intracerebral hemorrhagic, and 43 subarachnoid hemorrhagic). The hazard
      ratios (95% confidence interval) for total stroke with adherence to 0
      (reference), 1, 2, 3, 4, 5, and 6/7 ideal CVH metrics were: 1, 0.92 (0.69-1.23),
      0.69 (0.52-0.92), 0.52 (0.39-0.68), 0.38 (0.28-0.51), 0.27 (0.18-0.40), and 0.24
      (0.11-0.54), respectively (P trend <0.01), after adjusting for age, sex,
      education, income, and hospital. Similar inverse associations were observed for
      both ischemic and intracerebral hemorrhagic stroke (both P trend <0.01).
      CONCLUSIONS: We observed a clear inverse gradient relationship between the number
      of ideal CVH metrics and the risk of stroke in a Chinese population, supporting
      the importance of ideal health behaviors and factors in stroke prevention.

PMID- 23868277
TI  - Age-dependent exacerbation of white matter stroke outcomes: a role for oxidative
      damage and inflammatory mediators.
AB  - BACKGROUND AND PURPOSE: Subcortical white matter stroke (WMS) constitutes up to
      30% of all stroke subtypes. Mechanisms of oligodendrocyte and axon injury and
      repair play a central role in the damage and recovery after this type of stroke,
      and a comprehensive study of these processes requires a specialized experimental
      model that is different from common large artery, gray matter stroke models.
      Diminished recovery from stroke in aged patients implies that damage and repair
      processes are affected by advanced age, but such effects have not been studied in
      WMS. METHODS: WMS was produced with focal microinjection of the vasoconstrictor
      N5-(1-iminoethyl)-L-ornithine into the subcortical white matter ventral to the
      mouse forelimb motor cortex in young adult (2 months), middle-aged (15 months),
      and aged mice (24 months). RESULTS: WMS produced localized oligodendrocyte cell
      death with higher numbers of apoptotic cells and greater oxidative damage in aged
      brains than in young-adult brains. Increased expression of monocyte chemotactic
      protein-1 and tumor necrosis factor-alpha in motor cortex neurons correlated with
      a more distributed microglial activation in aged brains 7 days after WMS. At 2
      months, aged mice displayed increased white matter atrophy and greater loss of
      corticostriatal connections compared with young-adult mice. Behavioral testing
      revealed an age-dependent exacerbation of forelimb motor deficits caused by the
      stroke, with decreased long-term functional recovery in aged animals.
      CONCLUSIONS: Age has a profound effect on the outcome of WMS, with more prolonged
      cell death and oxidative damage, increased inflammation, greater secondary white
      matter atrophy, and a worse behavioral effect in aged versus young-adult mice.

PMID- 23868278
TI  - The Stroke Impact Scale: validation in a UK setting and development of a SIS
      short form and SIS index.
AB  - BACKGROUND AND PURPOSE: The Stroke Impact Scale (SIS) covers 8 dimensions and a
      composite disability score. This study evaluates the SIS in the UK context, and
      develops a single index and an 8-item short form. METHODS: Patients with a
      diagnosis of stroke were recruited through general practices in London and the
      North-West of England. Patients completed the SIS and the EQ-5D. RESULTS:
      Internal consistency of the SIS dimensions and the disability score ranged from
      alpha 0.86 to 0.95. Complete data were available on 73 questionnaires (48.34%).
      Factor analysis suggested the 8 domains could be aggregated into a single index.
      A short-form SIS (SF-SIS) index was created by summing 1 item per dimension.
      Selected items were those that most highly correlated with their respective
      domain score (rho ranged from 0.77-0.94, P<0.001). The SF-SIS index scores were
      highly correlated with those gained from the parent form (rho=0.98; P<0.001). The
      correlation of the SIS index and SF-SIS index with the EQ-5D was identical
      (rho=0.83; P<0.001). The disability score, whether scored from the dimensions of
      the SIS, or relevant items on the SF-SIS, were highly correlated (rho=0.97;
      P<0.001). CONCLUSIONS: The SIS covers aspects of health, which are of importance
      to stroke patients, and the dimensions were found to have high levels of internal
      consistency in the UK context. The amount of incomplete data suggests that the
      length of the questionnaire may present a substantial patient burden. In
      comparison to the parent form the SF-SIS can accurately provide the disability
      score and overall index score with considerable brevity.

PMID- 23868279
TI  - Unilateral versus bilateral upper limb training after stroke: the Upper Limb
      Training After Stroke clinical trial.
AB  - BACKGROUND AND PURPOSE: Unilateral and bilateral training protocols for upper
      limb rehabilitation after stroke represent conceptually contrasting approaches
      with the same ultimate goal. In a randomized controlled trial, we compared the
      merits of modified constraint-induced movement therapy, modified bilateral arm
      training with rhythmic auditory cueing, and a dose-matched conventional
      treatment. Modified constraint-induced movement therapy and modified bilateral
      arm training with rhythmic auditory cueing targeted wrist and finger extensors,
      given their importance for functional recovery. We hypothesized that modified
      constraint-induced movement therapy and modified bilateral arm training with
      rhythmic auditory cueing are superior to dose-matched conventional treatment.
      METHODS: Sixty patients, between 1 to 6 months after stroke, were randomized over
      3 intervention groups. The primary outcome measure was the Action Research Arm
      test, which was conducted before, directly after, and 6 weeks after intervention.
      RESULTS: Although all groups demonstrated significant improvement on the Action
      Research Arm test after intervention, which persisted at 6 weeks follow-up, no
      significant differences in change scores on the Action Research Arm test were
      found between groups postintervention and at follow-up. CONCLUSIONS: Modified
      constraint-induced movement therapy and modified bilateral arm training with
      rhythmic auditory cueing are not superior to dose-matched conventional treatment
      or each other in improving upper limb motor function 1 to 6 months after stroke.
      CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier:
      NTR1665.

PMID- 23868280
TI  - Germ-line and somatic DICER1 mutations in a pleuropulmonary blastoma.

PMID- 23868282
TI  - Vascular endothelial growth factor and amyotrophic lateral sclerosis: the
      interplay with exercise and noninvasive ventilation.
AB  - INTRODUCTION: We evaluated plasma vascular endothelial growth factor (VEGF)
      levels in patients with amyotrophic lateral sclerosis (ALS) with reference to the
      effects of respiratory failure, noninvasive ventilation (NIV), and exercise.
      METHODS: We studied plasma VEGF levels in 83 ALS patients, 20 healthy controls,
      and 10 patients with other disorders. There were 4 groups of ALS patients: G1, 27
      patients without respiratory problems; G2, 14 patients stabilized on nocturnal
      NIV; G3, 30 patients presenting with respiratory failure; G4, 12 patients on an
      aerobic exercise protocol. RESULTS: VEGF plasma levels did not differ
      significantly between ALS patients and controls, or between ALS groups. In G3,
      the mean VEGF levels increased 75% during NIV. In G4, the mean VEGF level
      increased by 300% during the exercise program. VEGF levels did not change during
      the course of the disease. CONCLUSIONS: VEGF levels in ALS depend on changes in
      ventilation and exercise but are probably not affected by the disease process
      itself.

PMID- 23868281
TI  - Breath tests to phenotype drug disposition in oncology.
AB  - Breath tests (BTs) have been investigated as diagnostic tools to phenotype drug
      disposition in cancer patients in the pursuit to individualize drug treatment.
      The choice of the right phenotype probe is crucial and depends on the metabolic
      pathway of the anticancer agent of interest. BTs using orally or intravenously
      administered selective non-radioactive (13)C-labeled probes to non-invasively
      evaluate dihydropyrimidine dehydrogenase, cytochrome P450 (CYP) 3A4, and CYP2D6
      enzyme activity have been published. Clinically, a (13)C-dextromethorphan BT to
      predict endoxifen levels in breast cancer patients and a (13)C-uracil BT to
      predict fluoropyrimidine toxicity in colorectal cancer patients are most
      promising. However, the clinical benefit and cost effectiveness of these
      phenotype BTs need to be determined in order to make the transition from an
      experimental setting to clinical practice as companion diagnostic tests. 

PMID- 23868283
TI  - A pheromone analogue affects the evaporation rate of (+)-disparlure in Lymantria
      dispar.
AB  - BACKGROUND: The gypsy moth Lymantria dispar L. is a widespread pest that causes
      economic damage to cork oak forests. Females produce the sex pheromone (+)
      (7R,8S)-epoxy-2-methyloctadecane, known as (+)-disparlure [(+)D], for long
      distance attraction of conspecific males. A (+)D analogue, 2-decyl-1
      oxaspiro[2.2]pentane (OXP-01), neither stimulating nor attractive by itself,
      causes short-time inhibition of male response in a 1:1 blend with (+)D. The
      authors investigated whether and how the biological activity of the natural
      pheromone is affected by OXP-01 on a long-time basis (up to 16 days), also by
      looking at possible physicochemical reciprocal interactions. RESULTS: Blending of
      (+)D with OXP-01 decreased, under low evaporation rate, the pheromone
      effectiveness, as assessed by electroantennogram recordings. In male trappings,
      within the first 24 h, OXP-01 decreased and later enhanced the blend
      attractiveness, but only under high evaporation rate. Gas chromatography-mass
      spectroscopy indicates that quantitative retrieval of (+)D from blend cartridges
      is higher than for pure pheromone, and nuclear magnetic resonance measurements
      show that OXP-01 produces, possibly by Van der Waals interactions, a bimolecular
      entity with pheromone causing retention and lengthening of its attractiveness
      over time. CONCLUSION: The biological and physicochemical interactions between
      (+)D and OXP-01 may provide valuable information for the optimisation of
      pheromone-based control strategies for gypsy moths.

PMID- 23868284
TI  - Fractional polynomial adjustment for time-varying covariates in a self-controlled
      case series analysis.
AB  - The self-controlled case series method is a statistical approach to investigating
      associations between acute outcomes and transient exposures. The method uses
      cases only and compares time at risk after the transient exposure with time at
      risk outside the exposure period within an individual, using conditional Poisson
      regression. The risk of outcome and exposure often varies over time, for example,
      with age, and it is important to allow for such time dependence within the
      analysis. The standard approach for modelling time-varying covariates is to split
      observation periods into blocks according to categories of the covariate and then
      to model the relationship using indicators for each category. However, this can
      be inefficient and can lead to problems with collinearity if the exposure occurs
      at approximately the same time in all individuals. As an alternative, we propose
      using fractional polynomials to model the relationship between the time-varying
      covariate and incidence of the outcome. We present the results from an analysis
      exploring the association between rotavirus vaccination and intussusception risk
      as well as a simulation study. We conclude that fractional polynomials provide a
      useful approach to adjusting for time-varying covariates but that it is important
      to explore the sensitivity of the results to the number of categories and the
      method of adjustment.

PMID- 23868285
TI  - Rapid spontaneous alloying between Pd nanocubes and Ag nanoparticles in aqueous
      solution at ambient temperature.
AB  - Rapid spontaneous alloying between Pd nanocubes and spherical or triangular Ag
      nanoparticles was studied in an aqueous solution at ambient temperature using
      transmission electron microscopy (TEM), TEM-energy-dispersed X-ray spectroscopy
      (EDS), XRD, and UV-Vis spectroscopy of product particles. The results show that
      alloying occurs between Ag particles and Pd cubes and finishes within a few
      seconds, preserving the cubic shape with maximum Ag content of approximately 22%.

PMID- 23868286
TI  - Vessel remodeling and plaque distribution in side branch of complex coronary
      bifurcation lesions: a grayscale intravascular ultrasound study.
AB  - To investigate vessel remodeling and plaque distribution in side branch (SB) of
      true coronary bifurcation lesions with SB disease extending from its ostium. A
      total of 62 patients with single de novo true bifurcation lesions with SB with
      severe and extensive disease were enrolled. Of that, 45 patients/lesions
      underwent pre-intervention intravascular ultrasound (IVUS) at the SB. Left
      anterior descending was the most prevalent target vessel (>85%). All lesions had
      significant involvement of both branches of the bifurcation, and the majority
      were classified as type 1,1,1 according to the Medina classification. Considering
      the subset with IVUS imaging, mean lesion length, reference diameter and %
      diameter stenosis in the SB were 8.88 +/- 4.61 mm, 2.68 +/- 0.59, and 70.2 +/-
      16.0%, respectively. Also, mean proximal (take-off) and distal (carina) angles
      were 142.3 +/- 21.9 degrees  and 60.7 +/- 22.4 degrees , respectively. At minimum
      lumena area (MLA) site, mean external elastic membrane and MLA cross-sectional
      areas were 6.70 +/- 2.08 and 1.87 +/- 0.93 mm2, respectively; given that the mean
      distance measured between the SB origin and MLA site was <1 mm. In addition, mean
      plaque burden was 67.9% and mean remodeling index was 0.78 +/- 0.21. Importantly,
      only 9 cases out of 45 presented remodeling index > 1.0. Also, plaque
      distribution analysis within the SB ostium demonstrated preferable plaque
      positioning in the opposite side to the flow divider. In conclusions, significant
      negative remodeling is a frequent encounter in SB of complex coronary bifurcation
      lesions presenting with extensive and severe disease; in addition, plaque
      distribution in the SB ostium appears to be asymmetric in relation to the parent
      vessel, as plaque burden is mostly found in regions of low wall shear stress
      including the opposite side to the flow divider within the bifurcation anatomy.

PMID- 23868287
TI  - Comparative analysis of lumen enlargement mechanisms achieved with the
      bifurcation dedicated BiOSS) stent versus classical coronary stent implantations
      by means of provisional side branch stenting strategy: an intravascular
      ultrasound study.
AB  - The aim of this study was to analyze the mechanisms of lumen enlargement in
      bifurcation lesions, as assessed by intravascular ultrasound (IVUS), after
      percutaneous treatment with classic provisional "T" stenting with conventional
      drug-eluting stents (DES) versus bifurcation dedicated BiOSS (Balton, Warsaw,
      Poland) stent. In this prospective study between Jan and Dec/11, 32 patients with
      single de novo coronary bifurcation lesions suitable for treatment with BiOSS
      stents were randomized (1:1). IVUS method included pre- and post-procedure
      analysis in the parent vessel. Vessel, lumen and plaque cross-sectional areas
      were determined at the target lesion [minimum lumen area (MLA) site], proximal
      limb, distal limb, and "window"-defined as the segment between the carina (flow
      divider) and the vessel wall at the level of the side branch inflow. All lesions
      were treated with provisional approach and only 1 case in BiOSS group had a stent
      implanted in the side branch. Angiographic and IVUS results including MLA at the
      target site and proximal/distal references were similar. However, mean window
      length-largest diameter within the window, was similar at baseline, but BiOSS
      measured significantly longer at postprocedure (2.21 +/- 0.37 vs. 1.76 +/- 0.52
      mm, p = 0.01). In addition, the magnitude of changes in vessel (27 +/- 24% vs. 9
      +/- 10%, p = 0.01) and plaque (2 +/- 26% vs. -2 +/- 26%, p = 0.02) areas at the
      window were significantly different for DES versus BiOSS groups, respectively.
      The contribution of vessel extension for lumen enlargement represented 54 versus
      43%, 130 versus 46%, 98 versus 80% and 51 versus 19% of the result achieved at
      the proximal limb, window, distal limb and MLA sites for DES versus BiOSS,
      respectively; as for plaque re-distribution, results were 36 versus 57%, -30
      versus 54%, 2 versus 20%, and 49 versus 81%, at the proximal limb, window, distal
      limb and MLA sites, respectively. These results suggest different mechanisms of
      lumen enlargement comparing conventional DES versus BiOSS dedicated bifurcation
      stent, which can impact side branch compromise during procedure.

PMID- 23868288
TI  - Audit of rapid access introduction reveals high prevalence of prostate cancer in
      Western Region.
AB  - INTRODUCTION: Men with symptoms suggestive of prostate cancer are now directly
      referred by their general practitioners to rapid access prostate assessment
      clinics (RAPACs). This service implements recommendations outlined by the
      National Cancer Control Programme. The RAPAC was introduced at Galway University
      Hospital, Galway, Ireland in June 2009, aiming to structure GP referral of
      patients with suspected prostate cancer to a urology service. AIMS: The aims of
      this study are to assess our initial experience with particular emphasis on
      access times, patient demographics, detection rates and treatment outcomes.
      METHODS: Data on all patients presenting to the RAPAC during the preliminary 2
      year period have been gathered prospectively and analysed using standard
      parametric analysis methods. RESULTS: A total of 1,106 patients were reviewed at
      278 clinic sessions during the initial 2-year period. The average waiting time to
      first clinic visit was 18 days (12-39 days). The mean age of referral to the
      clinic is 65 years (44-88 years). The mean PSA is 16.31 g/dL (0.4-845 g/dL). Of
      the 1106 patients undergoing TRUS biopsies, 503 (45.5 %) patients were diagnosed
      with prostate cancer. Further analysis patient demographics and cancer grading is
      presented in the article. Seventy-one patients (14.1 %) underwent radical
      retropubic prostatectomy. Sixty-seven patients (13.3 %) are being followed on an
      active monitoring programme, whilst 235 (56.7 %) received primary treatment with
      external beam radiotherapy and 68 (13.5 %) received brachytherapy. CONCLUSION:
      This data highlight the necessity of a RAPAC to streamline the provision of
      prostate cancer services in the west of Ireland.

PMID- 23868289
TI  - Advances in turbulent mixing techniques to study microsecond protein folding
      reactions.
AB  - Recent experimental and computational advances in the protein folding arena have
      shown that the readout of the one-dimensional sequence information into three
      dimensional structure begins within the first few microseconds of folding. The
      initiation of refolding reactions has been achieved by several means, including
      temperature jumps, flash photolysis, pressure jumps, and rapid mixing methods.
      One of the most commonly used means of initiating refolding of chemically
      denatured proteins is by turbulent flow mixing with refolding dilution buffer,
      where greater than 99% mixing efficiency has been achieved within 10's of
      microseconds. Successful interfacing of turbulent flow mixers with complementary
      detection methods, including time-resolved Fluorescence Spectroscopy (trFL),
      Forster Resonance Energy Transfer, Circular Dichroism, Small-Angle X-ray
      Scattering, Hydrogen Exchange followed by Mass Spectrometry and Nuclear Magnetic
      Resonance Spectroscopy, Infrared Spectroscopy (IR), and Fourier Transform IR
      Spectroscopy, has made this technique very attractive for monitoring various
      aspects of structure formation during folding. Although continuous-flow (CF)
      mixing devices interfaced with trFL detection have a dead time of only 30 us,
      burst phases have been detected in this time scale during folding of peptides and
      of large proteins (e.g., CheY and TIM barrels). Furthermore, a major limitation
      of the CF mixing technique has been the requirement of large quantities of
      sample. In this brief communication, we will discuss the recent flurry of
      activity in micromachining and microfluidics, guided by computational
      simulations, which are likely to lead to dramatic improvements in time resolution
      and sample consumption for CF mixers over the next few years.

PMID- 23868291
TI  - Strand invasion of DNA quadruplexes by PNA: comparison of homologous and
      complementary hybridization.
AB  - Molecular recognition of DNA quadruplex structures is envisioned to be a strategy
      for regulating gene expression at the transcriptional level and for in situ
      analysis of telomere structure and function. The recognition of DNA quadruplexes
      by peptide nucleic acid (PNA) oligomers is presented here, with a focus on
      comparing complementary, heteroduplex-forming and homologous, heteroquadruplex
      forming PNAs. Surface plasmon resonance and optical spectroscopy experiments
      demonstrated that the efficacy of a recognition mode depended strongly on the
      target. Homologous PNA readily invades a quadruplex derived from the promoter
      regulatory region found upstream of the MYC proto-oncogene to form a
      heteroquadruplex at high potassium concentration mimicking the intracellular
      environment, whereas complementary PNA exhibits virtually no hybridization. In
      contrast, complementary PNA is superior to the homologous in hybridizing to a
      quadruplex modeled on the human telomere sequence. The results are discussed in
      terms of the different structural morphologies of the quadruplex targets and the
      implications for in vivo recognition of quadruplexes by PNAs. 

PMID- 23868292
TI  - The dimeric form of the unphosphorylated response regulator BaeR.
AB  - Bacterial response regulators (RRs) can regulate the expression of genes that
      confer antibiotic resistance; they contain a receiver and an effector domain and
      their ability to bind DNA is based on the dimerization state. This is triggered
      by phosphorylation of the receiver domain by a kinase. However, even in the
      absence of phosphorylation RRs can exist in equilibrium between monomers and
      dimers with phosphorylation shifting the equilibrium toward the dimer form. We
      have determined the crystal structure of the unphosphorylated dimeric BaeR from
      Escherichia coli. The dimer interface is formed by a domain swap at the receiver
      domain. In comparison with the unphosphorylated dimeric PhoP from Mycobacterium
      tuberculosis, BaeR displays an asymmetry of the effector domains. 

PMID- 23868293
TI  - Effect of silanized nanosilica addition on remineralizing and mechanical
      properties of experimental composite materials with amorphous calcium phosphate.
AB  - OBJECTIVES: Experimental composite resins with amorphous calcium phosphate (ACP)
      have the potential to regenerate demineralized tooth structures. The aim of the
      study was to investigate the effect of the addition of silanized silica
      nanofillers to the ACP-based composites on their mechanical properties and the
      kinetics of calcium and phosphate release. MATERIALS AND METHODS: The test
      materials comprised 5 wt% (5-ACP) or 10 wt% (10-ACP) of silanized silica admixed
      to the 40 wt% ACP and 50 or 55 wt% resin. The ACP control (0-ACP) contained 40
      wt% ACP and 60 wt% resin. Additionally, composite material CeramX (Dentsply,
      Germany) was included as control. Three-point bending test was performed to
      calculate flexural strength and modulus of elasticity. Inductively coupled plasma
      atomic emission spectroscopy was used for measurement of ion release. The
      micromorphology of calcium phosphate depositions on composite samples has been
      qualitatively evaluated using a scanning electron microscope. The results were
      analyzed using Mann-Whitney and Wilcoxon rank sum tests (alpha < 0.05). RESULTS:
      Ion release was enhanced by the silica fillers, when compared to the 0-ACP.
      Although not statistically significant, flexural strength of 10-ACP was improved
      by 46 % compared to 0-ACP. Flexural modulus of 5-ACP was significantly higher
      than 0-ACP. CONCLUSIONS: The admixture of silanized fillers seems to be a
      promising approach for the improvement of mechanical and remineralizing
      properties of ACP composite resins. CLINICAL RELEVANCE: ACP-based composite
      resins with modified composition could serve as an effective remineralizing aid
      as base materials in restorative dental medicine.

PMID- 23868294
TI  - Overexpression of chemerin was associated with tumor angiogenesis and poor
      clinical outcome in squamous cell carcinoma of the oral tongue.
AB  - OBJECTIVE: The present study aimed to explore expression and clinical
      significance of chemerin, a newly discovered adipokine, in squamous cell
      carcinoma of the oral tongue (SCCOT). METHODS: mRNA expression of chemerin in 19
      pairs of fresh SCCOT samples matched with peritumoral mucosa tissues was
      quantified by real-time quantitative transcription polymerase chain reaction (qRT
      PCR). Chemerin protein expression and microvessel density (MVD) were measured by
      immunohistochemistry on 147 cases of primary SCCOT specimen and their
      corresponding peritumoral noncancerous tissues. The relationship of chemerin
      expression with angiogenesis, clinicopathologic parameters, and cancer-related
      survival of patients was evaluated. RESULTS: Both qRT-PCR and
      immunohistochemistry results revealed that chemerin was overexpressed in SCCOT
      compared with peritumoral noncancerous tissues (P < 0.01). Overexpression of
      chemerin in SCCOT was significantly associated with poor differentiation, lymph
      node metastasis, and high clinical stage (P = 0.000, 0.012, and 0.015,
      respectively). In addition, overexpression of chemerin was positively related to
      MVD in SCCOT (r = 0.671, P = 0.002). SCCOT patients with overexpressed chemerin
      had a shorter cancer-related survival (P = 0.027). Moreover, multivariate
      survival analysis indicated that chemerin was an independent prognostic factor
      for SCCOT patients (P = 0.016). CONCLUSION: These results demonstrated that
      overexpression of chemerin in SCCOT was correlated with tumor angiogenesis and
      poor clinical outcomes of SCCOT patients. CLINICAL RELEVANCE: Our research
      implied that chemerin was a novel prognostic factor for SCCOT patients, and
      chemerin could be a new therapeutic target for regulating tumor angiogenesis and
      blocking tumor progression.

PMID- 23868295
TI  - Characterization of the sugar-O-methyltransferase LobS1 in lobophorin
      biosynthesis.
AB  - Lobophorins A (1) and B (2) belong to a large group of spirotetronate natural
      products with potent antibacterial and antitumor activities. The cloning of the
      lobophorin biosynthesis gene cluster from the deep-sea-derived Streptomyces sp.
      SCSIO 01127 identified a sugar-O-methyltransferase-encoding gene lobS1. The lobS1
      inactivation mutant accumulated two new lobophorin analogs 3 and 4, different
      from 1 and 2 by lacking the 4-methyl group at the terminal L-digitoxose,
      respectively. Biochemical experiments verified that LobS1 was a SAM-dependent
      sugar-O-methyltransferase that required divalent metal ions for better activity.
      Antibacterial assays revealed compounds 3 and 4 were generally less potent than
      compounds 1 and 2. These findings suggest that the methylation on the terminal
      digitoxose by LobS1 tailors lobophorin biosynthesis and highlights the importance
      of this methylation for antibacterial potence.

PMID- 23868296
TI  - Yeast arming by the Aga2p system: effect of growth conditions in galactose on the
      efficiency of the display and influence of expressing leucine-containing
      peptides.
AB  - The amino or carboxy-terminal regions of certain cell wall proteins are capable
      of anchoring foreign proteins or peptides on the cell wall of the yeast
      Saccharomyces cerevisiae. This possibility has resulted in the development of a
      methodology known as yeast display which has powerful applications in
      biotechnology, pharmacy, and medicine. This work describes the results of
      experiments in which the agglutinin Aga2p protein is used as an anchor and
      several leucine-based peptides have been introduced into its N-terminal or C
      terminal position. We found that the sequence of these peptides can affect
      plasmid stability, growth kinetics, and levels of the fusion protein displayed,
      and we analyzed how the incubation conditions influence these parameters.
      Besides, we show that the introduction of these small peptides can modify the
      properties of cell cover; in particular, fusing five or ten leucine residues to
      the Aga2p protein results in greater hydrophobicity of the cell wall and also in
      increased resistance to the presence of the organic solvents acetonitrile and
      ethanol and to high salt concentrations. The introduction of the RLRLL sequence
      also results in higher resistance to the exposure of yeast cells to NaCl stress. 

PMID- 23868297
TI  - Increased production of gamma-lactones from hydroxy fatty acids by whole
      Waltomyces lipofer cells induced with oleic acid.
AB  - Among several fatty acids tested, oleic acid was selected as the most efficient
      inducer for the production of 4-hydroxydodecanoic acid, a metabolite of beta
      oxidation, by Waltomyces lipofer. Cells were induced by incubation for 12 h in a
      medium containing 10 g l(-1) yeast extract, 10 g l(-1) peptone, 5 g l(-1) oleic
      acid, 1 g l(-1) glucose, and 0.05 % (w/v) Tween 80. The optimal reaction
      conditions for the production of gamma-lactones by induced cells were pH 6.5, 35 
      degrees C, 200 rpm, 0.71 M Tris, 60 g l(-1) hydroxy fatty acid, and 20 g l(-1)
      cells. Non-induced cells produced 38 g l(-1) gamma-dodecalactone from 60 g l(-1)
      10-hydroxystearic acid after 30 h, with a conversion yield of 63 % (w/w) and a
      productivity of 1.3 g l(-1) h(-1) under the optimized conditions, whereas induced
      cells produced 51 g l(-1) gamma-dodecalactone from 60 g l(-1) 10-hydroxystearic
      acid after 30 h, with a conversion yield of 85 % (w/w) and a productivity of 1.7
      g l(-1) h(-1). The conversion yield and productivity of induced cells were 22 %
      and 1.3-fold higher, respectively, than those of non-induced cells. Induced cells
      also produced 28 g l(-1) gamma-decalactone and 12 g l(-1) gamma-butyrolactone
      from 60 g l(-1) 12-hydroxystearic acid and 60 g l(-1) 10-hydroxydecanoic acid,
      respectively, after 30 h. The concentration, conversion yield, and productivity
      of gamma-dodecalactone and gamma-decalactone are the highest reported thus far.
      This is the first study on the biotechnological production of gamma
      butyrolactone. 

PMID- 23868298
TI  - Pullulan production and physiological characteristics of Aureobasidium pullulans
      under acid stress.
AB  - In this study, batch processes of pullulan production by Aureobasidium pullulans
      CCTCC M 2012259 under different pH environments were evaluated. The pH of the
      medium decreased quickly to an acid stress condition under batch fermentation
      without pH control. A higher pullulan production was always obtained with a lower
      biomass under a given glucose concentration with constant pH control, and vice
      versa. Based on the nonlinear regression analysis of the results obtained from
      diverse pH control modes, a constant controlled pH of 3.8 was predicted as an
      optimum pH for efficient pullulan production using a one-element cubic equation.
      A maximum pullulan concentration of 26.8 g/L and a minimum biomass of 8.1 g/L
      were achieved under the optimal pH of 3.8, which were in good agreement with the
      results predicted by the mathematical model. Further information on the
      physiological characteristics of A. pullulans CCTCC M 2012259 such as
      intracellular pH, NADH/NAD(+), ATP/ADP, and glutathione generation under moderate
      or severe acidic conditions were investigated, and the results presented more
      evidence on why pullulan biosynthesized with high efficiency under moderate acid
      stress (e.g., pH 3.8), which would also help us to better understand the response
      of the cells to acid stress. 

PMID- 23868299
TI  - Pheochromocytoma in an 8-year-old patient with multiple endocrine neoplasia type
      2A: implications for screening.
AB  - Childhood pheochromocytoma in the setting of multiple endocrine neoplasia type 2
      (MEN2) remains rare and has not been reported under the age of 12. We present an
      8-year-old female with known MEN 2A, C634Y RET mutation, diagnosed with a 6 cm
      pheochromocytoma requiring laparoscopic adrenalectomy. Given this patient's age
      at diagnosis, screening guidelines should recommend annual screening beginning at
      age 8 for patients with MEN 2B or MEN 2A codons 630 or 634 RET mutations.

PMID- 23868305
TI  - Neuroprotective effects of nicotinamide N-methyltransferase and its metabolite 1
      methylnicotinamide.
AB  - Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) catalyses the N-methylation
      of nicotinamide to 1-methylnicotinamide (MeN). We have previously shown that the
      ectopic expression of NNMT in SH-SY5Y human neuroblastoma cells increased
      adenosine triphosphate synthesis and complex I activity, effects of which were
      replicated by the addition of MeN. In this study, we investigated whether NNMT
      expression in SH-SY5Y conferred protection against mitotoxicity induced by
      rotenone, potassium cyanide (KCN), 2,4-dinitrophenol, and 6-hydroxydopamine, and
      whether any effects observed were mediated via increased MeN production. NNMT
      expression abolished the toxic effects of KCN, 2,4-dinitrophenol, and 6
      hydroxydopamine, and reduced that of rotenone. In contrast, although MeN
      significantly reduced the toxicity of rotenone, it had no effect upon the
      toxicity of KCN, 2,4-dinitrophenol, and 6-hydroxydopamine. These data show that
      NNMT is cytoprotective against toxins that inhibit various aspects of
      mitochondrial function, and that these are not mediated solely via increased MeN
      production, but in combination with other unidentified mechanisms.

PMID- 23868306
TI  - Sentinel node biopsy in lieu of neck dissection for staging oral cancer.
AB  - IMPORTANCE: Neck dissection is the standard staging procedure to ascertain the
      pathologic status of cervical lymph nodes in patients with oral cavity squamous
      cell carcinoma (OSCC), but it results in multiple morbidities. OBJECTIVE: To
      examine outcomes of patients with OSCC who underwent sentinel node biopsy (SNB)
      as the sole neck staging procedure. DESIGN: Retrospective review of patients who
      underwent SNB during the period 2005 through 2011. SETTING: National Cancer
      Institute-designated comprehensive cancer center. PARTICIPANTS: Thirty-eight
      patients with clinically T1 or T2N0 OSCC. INTERVENTIONS: Preoperative
      lymphoscintigraphy with intraoperative gamma probe localization was used.
      Sentinel lymph nodes were serially sectioned, formalin fixed, and examined at 3
      levels. All patients with positive SNB results underwent neck dissection, and the
      patients with negative SNB results were observed clinically. MAIN OUTCOMES AND
      MEASURES: Sensitivity and predictive value of SNB, recurrence rates, and disease
      specific survival rates. RESULTS: There were 18 T1 and 20 T2 tumors. Five
      patients had positive SNB results, of whom 3 had additional positive nodes on
      subsequent neck dissection. Two of 33 patients with negative SNB results
      developed a regional recurrence. The sensitivity and negative predictive value
      for staging the neck with SNB alone were 71% (5 of 7) and 94% (31 of 33),
      respectively. Mean follow-up was 31 months. The mean disease-free survival
      duration for patients with positive and negative SNB results was 30 and 65
      months, respectively (P = .08). The disease-specific survival rate for patients
      with positive and negative SNB results was 80% and 91%, respectively. There was
      no significant difference in disease-specific survival between patients with true
      negative and false-negative SNB results (34 vs 44 months; P = .38). CONCLUSIONS
      AND RELEVANCE: The majority of patients with positive results on SNB had
      additional positive nodes on neck dissection. A low rate of isolated neck
      recurrence was found in patients with negative results on SNB. Individuals with
      negative results on SNB exhibited better overall and disease-specific survival
      than those with positive results.

PMID- 23868315
TI  - Metabolomics: playing pinata with single cells.
AB  - Mass spectrometry advances in single-cell metabolomics enable the discovery of a
      new biological insight that is not accessible from population-level studies. A
      new study reveals that single baker's yeast cells provide sufficient material to
      study chemical and genetic inhibition of glycolysis and identifies metabolic
      subpopulations that would be invisible in bulk.

PMID- 23868316
TI  - Channels: Sticking to nooks and crannies.
AB  - Drug design for voltage-gated ion channels has long been hampered by the absence
      of crystal structures and the challenge of achieving subtype selectivity. A
      combination of mutagenesis, electrophysiology and molecular modeling has led to
      the identification of a new side pocket binding site for the small molecule Psora
      4 between the pore and the voltage-sensor domain of Kv1.5, offering opportunities
      to design allosteric ion channel modulators.

PMID- 23868318
TI  - Logical modelling of Drosophila signalling pathways.
AB  - A limited number of signalling pathways are involved in the specification of cell
      fate during the development of all animals. Several of these pathways were
      originally identified in Drosophila. To clarify their roles, and possible cross
      talk, we have built a logical model for the nine key signalling pathways
      recurrently used in metazoan development. In each case, we considered the
      associated ligands, receptors, signal transducers, modulators, and transcription
      factors reported in the literature. Implemented using the logical modelling
      software GINsim, the resulting models qualitatively recapitulate the main
      characteristics of each pathway, in wild type as well as in various mutant
      situations (e.g. loss-of-function or gain-of-function). These models constitute
      pluggable modules that can be used to assemble comprehensive models of complex
      developmental processes. Moreover, these models of Drosophila pathways could
      serve as scaffolds for more complicated models of orthologous mammalian pathways.
      Comprehensive model annotations and GINsim files are provided for each of the
      nine considered pathways. 

PMID- 23868317
TI  - Chemical reporters for biological discovery.
AB  - Functional tools are needed to understand complex biological systems. Here we
      review how chemical reporters in conjunction with bioorthogonal labeling methods
      can be used to image and retrieve nucleic acids, proteins, glycans, lipids and
      other metabolites in vitro, in cells as well as in whole organisms. By tagging
      these biomolecules, researchers can now monitor their dynamics in living systems
      and discover specific substrates of cellular pathways. These advances in chemical
      biology are thus providing important tools to characterize biological pathways
      and are poised to facilitate our understanding of human diseases. 

PMID- 23868319
TI  - Extremotolerance and resistance of lichens: comparative studies on five species
      used in astrobiological research I. Morphological and anatomical characteristics.
AB  - Lichens are symbioses of two organisms, a fungal mycobiont and a photoautotrophic
      photobiont. In nature, many lichens tolerate extreme environmental conditions and
      thus became valuable models in astrobiological research to fathom biological
      resistance towards non-terrestrial conditions; including space exposure,
      hypervelocity impact simulations as well as space and Martian parameter
      simulations. All studies demonstrated the high resistance towards non-terrestrial
      abiotic factors of selected extremotolerant lichens. Besides other adaptations,
      this study focuses on the morphological and anatomical traits by comparing five
      lichen species-Circinaria gyrosa, Rhizocarpon geographicum, Xanthoria elegans,
      Buellia frigida, Pleopsidium chlorophanum-used in present-day astrobiological
      research. Detailed investigation of thallus organization by microscopy methods
      allows to study the effect of morphology on lichen resistance and forms a basis
      for interpreting data of recent and future experiments. All investigated lichens
      reveal a common heteromerous thallus structure but diverging sets of
      morphological-anatomical traits, as intra-/extra-thalline mucilage matrices,
      cortices, algal arrangements, and hyphal strands. In B. frigida, R. geographicum,
      and X. elegans the combination of pigmented cortex, algal arrangement, and
      mucilage seems to enhance resistance, while subcortex and algal clustering seem
      to be crucial in C. gyrosa, as well as pigmented cortices and basal thallus
      protrusions in P. chlorophanum. Thus, generalizations on morphologically
      conferred resistance have to be avoided. Such differences might reflect the
      diverging evolutionary histories and are advantageous by adapting lichens to
      prevalent abiotic stressors. The peculiar lichen morphology demonstrates its
      remarkable stake in resisting extreme terrestrial conditions and may explain the
      high resistance of lichens found in astrobiological research. 

PMID- 23868320
TI  - Total artificial heart in the pediatric patient with biventricular heart failure.
AB  - Mechanical circulatory support emerged for the pediatric population in the late
      1980s as a bridge to cardiac transplantation. The Total Artificial Heart (TAH-t)
      (SynCardia Systems Inc., Tuscon, AZ) has been approved for compassionate use by
      the Food and Drug Administration for patients with end-stage biventricular heart
      failure as a bridge to heart transplantation since 1985 and has had FDA approval
      since 2004. However, of the 1,061 patients placed on the TAH-t, only 21 (2%) were
      under the age 18. SynCardia Systems, Inc. recommends a minimum patient body
      surface area (BSA) of 1.7 m(2), thus, limiting pediatric application of this
      device. This unique case report shares this pediatric institution's first
      experience with the TAH-t. A 14-year-old male was admitted with dilated
      cardiomyopathy and severe biventricular heart failure. The patient rapidly
      decompensated, requiring extracorporeal life support. An echocardiogram revealed
      severe biventricular dysfunction and diffuse clot formation in the left ventricle
      and outflow tract. The decision was made to transition to biventricular assist
      device. The biventricular failure and clot formation helped guide the team to the
      TAH-t, in spite of a BSA (1.5 m(2)) below the recommendation of 1.7 m(2). A
      computed tomography (CT) scan of the thorax, in conjunction with a novel three
      dimensional (3D) modeling system and team, assisted in determining appropriate
      fit. Chest CT and 3D modeling following implantation were utilized to determine
      all major vascular structures were unobstructed and the bronchi were open. The
      virtual 3D model confirmed appropriate device fit with no evidence of compression
      to the left pulmonary veins. The postoperative course was complicated by a left
      lung opacification. The left lung anomalies proved to be atelectasis and improved
      with aggressive recruitment maneuvers. The patient was supported for 11 days
      prior to transplantation. Chest CT and 3D modeling were crucial in assessing
      whether the device would fit, as well as postoperative complications in this
      smaller pediatric patient.

PMID- 23868321
TI  - Comparative antifeedant activities of polygodial and pyrethrins against
      whiteflies (Bemisia tabaci) and aphids (Myzus persicae).
AB  - BACKGROUND: Polygodial, a sesquiterpene dialdehyde of the drimane family, has
      been shown to have deterrent and antifeedant effects on various insect species,
      including Myzus persicae (Sulzer), Spodoptera spp. and Leptinotarsa decemlineata
      (Say). This compound may have potential as a broad-spectrum biocontrol agent,
      similar to pyrethrins, given that it was previously reported to improve yield
      when sprayed on barley fields. RESULTS: This study compares the deterrent effect
      of polygodial and pyrethrins against the silverleaf whitefly Bemisia tabaci
      (Gennadius) and the green peach aphid M. persicae in dual-choice assays using
      compound-coated tomato leaf discs. B. tabaci adults were deterred by polygodial
      at an ED50 (effective dose at which 50% of the insects are deterred) of about 25
      ug g(-1) fresh weight (FW), and green peach aphids at about 54 ug g(-1) FW.
      Bioassays were benchmarked with pyrethrins that had a 20-fold lower ED50 of
      approximately 1.4 ug g(-1) FW against whiteflies, but only a twofold lower ED50
      (about 28 ug g(-1) FW) against peach aphids. Polygodial showed moderate
      phytotoxic effects (score of 2 on a scale of 1-5) on tomato leaves at
      concentrations above the ED50 concentrations (>= 90 ug g(-1) FW). CONCLUSION: The
      sesquiterpene dialdehyde polygodial is 2-20 times less deterrent than pyrethrins,
      depending on the insect species, but it could provide a useful complement to
      pyrethrin sprays as it has a different mode of action, is food grade and has low
      volatility. However, a formulation that reduces the risks of phytotoxic effects
      should be developed.

PMID- 23868322
TI  - Synthesis and conformational analysis of macrocyclic peptides consisting of both
      alpha-helix and polyproline helix segments.
AB  - Macrocycles are interesting molecules because their topological features and
      constrained properties significantly affect their chemical, physical, biological,
      and self-assembling properties. In this report, we synthesized unique macrocyclic
      peptides composed of both an alpha-helix and a polyproline segment and analyzed
      their conformational properties. We found that the molecular stiffness of the rod
      like polyproline segment and the relative orientation of the two different
      helical segments strongly affect the efficiency of the macrocyclization reaction.
      Conformational analyses showed that both the alpha-helix and the polyproline II
      helix coexisted within the macrocyclic peptides and that the polyproline segment
      exerts significant effect on the overall helical stability and conformation of
      the alpha-helical segment.

PMID- 23868323
TI  - Mitochondrial trifunctional protein deficiency: a rare cause of adult-onset
      rhabdomyolysis.
AB  - INTRODUCTION: Mitochondrial trifunctional protein deficiency is a rare autosomal
      recessive disorder of mitochondrial fatty acid beta-oxidation that may be due to
      mutations in 2 different nuclear genes, HADHA and HADHB. Perturbation of this
      multienzyme complex compromises the oxidation of long-chain fatty acids, which
      leads to multiorgan dysfunction. Childhood- or adolescent-onset recurrent
      rhabdomyolysis is a common muscular manifestation and is preceded frequently by
      clinically overt peripheral neuropathy. METHODS: In this report we describe a
      patient with late adult-onset recurrent rhabdomyolysis. RESULTS: Despite normal
      sensory examination, nerve conduction studies showed a mild axonal peripheral
      neuropathy. The acylcarnitine profile showed elevated long-chain and 3-hydroxy
      long-chain acylcarnitine species. HADHA sequencing revealed known compound
      heterozygous mutations c.180+3A>G (p.Thr37SerfsX6) and c.1528G>C (p.Glu510Gln).
      During a 10-month follow-up period, he had no further episodes of rhabdomyolysis
      after appropriate dietary modifications. CONCLUSIONS: Mitochondrial trifunctional
      protein deficiency should be considered in patients with adult-onset recurrent
      rhabdomyolysis, especially in those with either clinically overt or subclinical
      peripheral neuropathy.

PMID- 23868324
TI  - Optimal adaptive two-stage designs for phase II cancer clinical trials.
AB  - In oncology, single-arm two-stage designs with binary endpoint are widely applied
      in phase II for the development of cytotoxic cancer therapies. Simon's optimal
      design with prefixed sample sizes in both stages minimizes the expected sample
      size under the null hypothesis and is one of the most popular designs. The search
      algorithms that are currently used to identify phase II designs showing
      prespecified characteristics are computationally intensive. For this reason, most
      authors impose restrictions on their search procedure. However, it remains
      unclear to what extent this approach influences the optimality of the resulting
      designs. This article describes an extension to fixed sample size phase II
      designs by allowing the sample size of stage two to depend on the number of
      responses observed in the first stage. Furthermore, we present a more efficient
      numerical algorithm that allows for an exhaustive search of designs. Comparisons
      between designs presented in the literature and the proposed optimal adaptive
      designs show that while the improvements are generally moderate, notable
      reductions in the average sample size can be achieved for specific parameter
      constellations when applying the new method and search strategy. 

PMID- 23868325
TI  - Stability of pristine and defective SnTe surfaces from first principles.

PMID- 23868326
TI  - New insights into intestinal secretion.

PMID- 23868327
TI  - Iron deficiency anaemia and cataracts in a patient with haemochromatosis.

PMID- 23868328
TI  - Selective inhibition of mucosal serotonin as treatment for IBD?

PMID- 23868330
TI  - Raising standards in UK TB control: introducing cohort review.
AB  - Cohort review has been used internationally to support tuberculosis (TB) control.
      We describe its first use in the UK by a London TB service. Improvements were
      noted in case management and contact tracing, weaknesses identified and important
      service changes put in place. Key areas of impact were directly observed therapy
      (DOT) provision (a greater proportion of cases offered DOT, and in response to
      low uptake resources diverted to create posts responsible for patient-centred DOT
      delivery), and contact tracing (more contacts per case screened and assessed).
      Cohort review enables whole system review and improvement. It has subsequently
      been adopted across the UK. 

PMID- 23868329
TI  - Characterization of a cold-adapted and salt-tolerant esterase from a
      psychrotrophic bacterium Psychrobacter pacificensis.
AB  - An esterase gene, est10, was identified from the genomic library of a deep-sea
      psychrotrophic bacterium Psychrobacter pacificensis. The esterase exhibited the
      optimal activity around 25  degrees C and pH 7.5, and maintained as high as 55.0
      % of its maximum activity at 0  degrees C, indicating its cold adaptation. Est10
      was fairly stable under room temperatures, retaining more than 80 % of its
      original activity after incubation at 40  degrees C for 2 h. The highest activity
      was observed against the short-chain substrate p-nitrophenyl butyrate (C4) among
      the tested p-nitrophenyl esters (C2-C16). It was slightly activated at a low
      concentration (1 mM) of Zn(2+), Mg(2+), Ba(2+), Ca(2+), Cu(2+), Fe(3+), urea and
      EDTA, but was inhibited by DTT and totally inactivated by PMSF. Interestingly,
      increased salinity considerably stimulated Est10 activity (up to 143.2 % of
      original activity at 2 M NaCl) and stability (up to 126.4 % after incubation with
      5 M NaCl for 6.5 h), proving its salt tolerance. 0.05 and 0.1 % Tween 20, Tween
      80, Triton X-100 and CHAPS increased the activity and stability of Est10 while
      SDS, CTAB had the opposite effect. Est10 was quite active after incubation with
      several 30 % organic solvents (methanol, DMSO, ethanediol) but exhibited little
      activity with 30 % isopropanol, ethanol, n-butanol and acetonitrile.

PMID- 23868331
TI  - Evaluating hypoxia during air travel in healthy infants.
AB  - Up to a third of ex-preterm infants flying near term exhibit pulse oxygen
      saturation (SpO2) of less than 85% during air travel. A hypoxia challenge test
      (HCT) is recommended to evaluate the requirement for in-flight supplemental O2.
      The validity of the HCT in healthy, term infants has not been reported. This
      study aimed to characterise the in-flight hypoxia response and the accuracy of
      the HCT to predict this response in healthy, term infants in the first year of
      life. Infants (n=24: (15 male)) underwent a HCT prior to commercial air travel
      during which parents monitored SpO2. Thirty-two flights were undertaken with six
      infants completing multiple flights. The median in-flight SpO2 nadir was 87% and
      significantly lower than the HCT SpO2 nadir (92%: p<0.001). Infants on seven
      flights recorded SpO2<85% with one infant recording a HCT with a SpO2 less than
      85%. There was marked variability in the in-flight SpO2 in the six infants who
      undertook multiple flights, and for three of these infants, the SpO2 nadir was
      both above and below 85%. We report that in healthy term infants an in-flight
      SpO2 below 85% is common and can vary considerably between flights and that the
      HCT poorly predicts the risk of in-flight hypoxia (SpO2<85%). As it is common for
      healthy term infants to have SpO2 less than 85% during air travel further
      research is needed to clarify whether this is an appropriate cut-off in this age
      group. 

PMID- 23868332
TI  - Electron delocalization is not a satisfactory explanation for the preference for
      branching in the alkanes.

PMID- 23868334
TI  - Suggested pathway to assess radiation safety of 18F-labeled PET tracers for first
      in-human studies.

PMID- 23868333
TI  - Design, construction, and characterization of a second-generation DARP in library
      with reduced hydrophobicity.
AB  - Designed ankyrin repeat proteins (DARPins) are well-established binding molecules
      based on a highly stable nonantibody scaffold. Building on 13 crystal structures
      of DARPin-target complexes and stability measurements of DARPin mutants, we have
      generated a new DARPin library containing an extended randomized surface. To
      counteract the enrichment of unspecific hydrophobic binders during selections
      against difficult targets containing hydrophobic surfaces such as membrane
      proteins, the frequency of apolar residues at diversified positions was
      drastically reduced and substituted by an increased number of tyrosines. Ribosome
      display selections against two human caspases and membrane transporter AcrB
      yielded highly enriched pools of unique and strong DARPin binders which were
      mainly monomeric. We noted a prominent enrichment of tryptophan residues during
      binder selections. A crystal structure of a representative of this library in
      complex with caspase-7 visualizes the key roles of both tryptophans and tyrosines
      in providing target contacts. These aromatic and polar side chains thus
      substitute the apolar residues valine, leucine, isoleucine, methionine, and
      phenylalanine of the original DARPins. Our work describes biophysical and
      structural analyses required to extend existing binder scaffolds and simplifies
      an existing protocol for the assembly of highly diverse synthetic binder
      libraries. 

PMID- 23868335
TI  - Acute heart failure with preserved ejection fraction: unique patient
      characteristics and targets for therapy.
AB  - Currently, there are 1.0 million annual hospital discharges for acute heart
      failure (AHF). The total cost of heart failure (HF) care in the United States is
      projected to increase to $53 billion in 2030, with the majority of costs (80 %)
      related to AHF hospitalizations. Approximately 50 % of AHF episodes occur in
      patients with preserved ejection fraction (HFpEF). There is a dearth of evidence
      based guidelines for the management of AHF in HFpEF patients. Here, we briefly
      review the epidemiology, pathophysiology, and treatment of AHF patients with
      HFpEF.

PMID- 23868336
TI  - Desktop nanofabrication with massively multiplexed beam pen lithography.
AB  - The development of a lithographic method that can rapidly define nanoscale
      features across centimetre-scale surfaces has been a long-standing goal for the
      nanotechnology community. If such a 'desktop nanofab' could be implemented in a
      low-cost format, it would bring the possibility of point-of-use nanofabrication
      for rapidly prototyping diverse functional structures. Here we report the
      development of a new tool that is capable of writing arbitrary patterns composed
      of diffraction-unlimited features over square centimetre areas that are in
      registry with existing patterns and nanostructures. Importantly, this instrument
      is based on components that are inexpensive compared with the combination of
      state-of-the-art nanofabrication tools that approach its capabilities. This tool
      can be used to prototype functional electronic devices in a mask-free fashion in
      addition to providing a unique platform for performing high-throughput nano- to
      macroscale photochemistry with relevance to biology and medicine. 

PMID- 23868337
TI  - Comparison of fecal continence and quality of life between intersphincteric
      resection and abdominoperineal resection plus perineal colostomy for ultra-low
      rectal cancer.
AB  - AIMS: The only two procedures for surgical treatment of ultra-low rectal cancer
      without a permanent abdominal stoma are the intersphincteric resection (ISR) and
      the abdominoperineal resection (APR) plus a perineal pseudocontinent colostomy
      (PCC). This study compared functional results and quality of life following these
      two techniques. METHODS: Between January 1995 and December 2011, 36 patients had
      undergone an ISR (n = 14) or a PPC (n = 22) for very low rectal cancer. The
      Cleveland Clinica Florida (Wexner) fecal incontinence questionnaire and the EORTC
      Quality of Life questionnaire QLQ-C30 and CR38 had been administered. RESULTS:
      There were no differences in gender, age, the interval between surgery and
      questionnaire responses, preoperative TNM staging, perioperative treatment, the
      laparoscopic approach and circumferential margin involvement rate between the
      groups. The ISR and PPC led to no difference in quality of life (Qol) and
      continence with a median Wexner score of respectively 11 and 10 (P = 0.403) and a
      fecal incontinence rate of 58.2% and 41% (P = 0.221). The incontinent patients
      had experienced worse social functioning and tended to have worse overall health.
      The patients who had undergone ISR had more defecation problems and evacuation
      difficulties. CONCLUSION: Qol and continence are similar between ISR and PPC.

PMID- 23868338
TI  - Disease, drug metabolism, and transporter interactions.

PMID- 23868339
TI  - Scientific Evidence and Controversies About Pioglitazone and Bladder Cancer:
      Which Lessons Can Be Drawn?
AB  - Pioglitazone, a peroxisome proliferator-activated receptors (PPAR) agonist, has
      been authorized for the management of type 2 diabetes since 1999 in the US and
      since 2000 in Europe. Since then, the risk of bladder cancer associated with
      pioglitazone use has been a serious concern. Following a warning from the Agence
      Francaise de Securite Sanitaire des Produits de Sante (Afssaps) [the French
      Agency for the Safety of Health Products], use of pioglitazone was suspended in
      France and Germany in June 2011. Elsewhere, restrictions on prescriptions were
      implemented, though for both the European Medicines Agency and the US Food and
      Drug Administration, the risk-benefit ratio remains favourable. Since the
      development of pioglitazone, its risk assessment has suffered from several
      inaccuracies such as its alleged specificity for the male rat, untrustworthy
      selective agonism for PPARgamma and mistaken risk evaluation in the large
      PROactive trial (PROspective pioglitAzone Clinical Trial In macroVascular
      Events), where one case with a benign tumour in the placebo group was counted as
      a cancer case. It took until 2011 for the epidemiological data to be sufficiently
      numerous and conclusive to initiate application of safety measures. Today, the
      increased risk of bladder cancer associated with pioglitazone seems to be real,
      but the absolute risk is relatively low. However, in the context of weak efficacy
      in an extensive population of patients exposed to pioglitazone, the risk-benefit
      balance is now difficult to assess, and prescription restrictions do not ensure
      safety. For future risk management, the authors propose several suggestions,
      which involve an increasing role of health authorities and academic
      organizations. 

PMID- 23868341
TI  - Dynamic expressions of Beclin 1 and tyrosine hydroxylase in different areas of 6
      hydroxydopamine-induced Parkinsonian rats.
AB  - Beclin 1, a regulator of the autophagy pathway, plays an important role in
      Parkinson's disease (PD). However, the crucial mechanism of Beclin 1 in PD
      remains unclear. Therefore, we investigated dynamic expressions of Beclin 1 and
      tyrosine hydroxylase (TH) in different brain areas of 6-OHDA-induced rats. Beclin
      1 and TH expressions were analyzed by flow cytometry and immunohistochemistry,
      respectively. The results showed that Beclin 1 expressions were low in the sham
      group, but rose significantly after 6-OHDA injection. In the striatum and cortex,
      Beclin 1 increased at 3 h, peaking at 12 h, while in the hippocampus, it
      increased at 3 h and peaked at 24 h, then it declined slowly and remained steady
      at 72 h. Beclin 1 expression in the striatum and cortex areas was higher than
      that of the hippocampus area at 12 h. In addition, the time-course of TH
      expression in the striatum was similar to that in the mesencephalon. TH
      expression declined dramatically between 0 and 12 h. Pearson analysis showed
      significant negative correlations between TH and Beclin 1 expression in the areas
      we analyzed. While TH expression declined gradually between 12 and 72 h,
      significant positive correlations between TH and Beclin 1 were detected during
      that interval. This indicated that activation of Beclin 1-dependent autophagy may
      inhibit the loss of TH-positive neurons.

PMID- 23868340
TI  - Neuroprotective effect of aqueous extract of Selaginella delicatula as evidenced
      by abrogation of rotenone-induced motor deficits, oxidative dysfunctions, and
      neurotoxicity in mice.
AB  - Oxidative stress is one of the mechanisms implicated to play a significant role
      in the pathophysiology of Parkinson's disease. Previously, we showed that an
      aqueous extract of Selaginella delicatula (SDAE) offered robust neuroprotection
      against rotenone (ROT) in a Drosophila model. In furtherance in the present
      study, we validated the neuroprotective efficacy of SDAE in a chronic ROT
      exposure model in mice. Initially, we assessed the propensity of SDAE to modulate
      the levels of endogenous markers in striatal region of mice. Subsequently, the
      neuroprotective efficacy of SDAE (100 mg/kg bw, 21 d) to mitigate ROT-induced
      striatal motor deficits, oxidative stress, and neurotoxicity was examined
      employing a co-exposure paradigm. We found significant attenuation of ROT-induced
      motor deficits (stride length and landing foot spread distance) among mice given
      SDAE supplements. Biochemical analysis revealed that ROT-induced elevation in the
      levels of oxidative markers in cytosol/mitochondria of striatum were normalized
      with SDAE supplements. In addition, SDAE also restored the ROT-induced elevation
      in the levels of oxidized and nitrated proteins. Further, SDAE also restored the
      activities of acetylcholinesterase and butyrylcholinesterase indicating its
      effect on cholinergic function. While ROT exposure caused significant
      perturbations in the activity levels of mitochondrial electron transport chain
      enzymes (complex I/II), membrane potential and activity of ATPases, these
      functions were restored to normalcy among mice receiving SDAE suggesting its
      effects on mitochondrial function. Since these data corroborate our previous
      findings in Drosophila system, we propose that the neuroprotective property of
      SDAE may be largely attributed to the antioxidant properties and its ability to
      attenuate mitochondrial dysfunction. However, studies employing dopaminergic cell
      models would enable us to identify specific molecular mechanism, by which SDAE
      exerts neuroprotective action.

PMID- 23868342
TI  - The effect of nitrogen rate on transgenic corn Cry3Bb1 protein expression.
AB  - BACKGROUND: Combining herbicide-resistant and Bacillus thuringiensis (Bt) traits
      in corn (Zea mays L.) hybrids may affect insect resistance management owing to
      volunteer corn. Some Bt toxins may be expressed at lower levels by nitrogen
      deficient corn roots. Corn plants with sublethal levels of Bt expression could
      accelerate the evolution of Bt resistance in target insects. The present
      objective was to quantify the concentration of Bt (Cry3Bb1) in corn root tissue
      with varying tissue nitrogen concentrations. RESULTS: Expression of Cry3Bb1 toxin
      in root tissue was highly variable, but there were no differences in the overall
      concentration of Cry3Bb1 expressed between roots taken from Cry3Bb1-positive
      volunteer and hybrid corn plants. The nitrogen rate did affect Cry3Bb1 expression
      in the greenhouse, less nitrogen resulted in decreased Cry3Bb1 expression, yet
      this result was not documented in the field. CONCLUSION: A positive linear
      relationship of plant nitrogen status on Cry3Bb1 toxin expression was documented.
      Also, high variability in Cry3Bb1 expression is potentially problematic from an
      insect resistance management perspective. This variability could create a mosaic
      of toxin doses in the field, which does not fit into the high-dose refuge
      strategy and could alter predictions about the speed of evolution of resistance
      to Cry3Bb1 in western corn rootworm Diabrotica virgifera virgifera LeConte.

PMID- 23868346
TI  - Welcome to the new JAMA Facial Plastic Surgery!

PMID- 23868345
TI  - Mnemosyne (Marie Spartali, 1844-1927): Julia Margaret Cameron.

PMID- 23868347
TI  - Taking evidence-based plastic surgery to the next level: report of the second
      summit on evidence-based plastic surgery.
AB  - Applying the principles of evidence-based medicine has the potential to
      drastically improve quality of care and patient outcomes. For this reason,
      evidence-based medicine has been held as one of the 15 most important
      developments in medicine within the past 100 years. In August of 2010, a broad
      coalition of leaders from numerous organizations representing societies, boards,
      journals, foundations, and academic institutions met in Colorado Springs,
      Colorado, for the first Evidence-Based Plastic Surgery Summit. The summit
      signaled a sea change in the approach of organized plastic surgery to the
      promotion of evidence-based medicine within the specialty. It was determined that
      a strategic, coordinated, and sustained effort to drive an evidence-based
      medicine culture would accelerate adoption and advance quality of care and
      patient safety. Over the past 2 years, many of the goals of the initial summit
      have been met. In order to take our evidence-based medicine efforts to the next
      level, a second summit was recently held to redefine goals, focus efforts,
      address barriers, and launch new initiatives with broad consensus. This article
      documents the outcomes of the second Evidence-Based Plastic Surgery Summit. 

PMID- 23868348
TI  - Importance of mucosal closure in nasal septal perforation repair.

PMID- 23868350
TI  - Characterization of hyaluronic acid and synovial fluid in stagnation point
      elongational flow.
AB  - Hyaluronic acid (HA) is an important biomacromolecule, which fulfils a number of
      vital physiological functions (especially in the joint synovial fluid) and also
      has consumer and pharmaceutical applications. HA solution properties have already
      been quite thoroughly characterized in response to steady shear flows but are
      less well understood in highly deforming extensional flows. In this study, flow
      induced birefringence measurements are made as a function of the strain rate in
      planar elongational flow at the stagnation point of a cross-slot device using HA
      solutions of a range of molecular weights (0.9*10(6) g mol(-1)<=Mw<=4.8*10(6) g
      mol(-1)) and at dilute concentrations. The results provide macromolecular
      relaxation times, molecular weight distributions and the extensional viscosities
      and Trouton ratios of the fluids. The HA relaxation time is found to vary as
      tau~Mw1.8, which is consistent with a partially solvated, expanded coil. An
      intrinsic Trouton ratio is defined, which varies as [Tr]~Mw2. The measurement of
      birefringence with strain rate is shown to be highly sensitive to the molecular
      weight distribution and can resolve subtle changes due to macromolecular
      degradation and the presence of fracture products. Mechanical degradation
      experiments in the cross-slots indicate midchain scission of HA macromolecules,
      strongly suggesting near full extension of the high-molecular weight fraction in
      the stagnation point extensional flow field. Taken together the results suggest a
      possible method for analysis of the HA in synovial fluid, and this concept is
      tested using synovial fluid obtained from porcine tarsal joint.

PMID- 23868351
TI  - Food web de-synchronization in England's largest lake: an assessment based on
      multiple phenological metrics.
AB  - Phenological changes have been observed globally for marine, freshwater and
      terrestrial species, and are an important element of the global biological
      'fingerprint' of climate change. Differences in rates of change could
      desynchronize seasonal species interactions within a food web, threatening
      ecosystem functioning. Quantification of this risk is hampered by the rarity of
      long-term data for multiple interacting species from the same ecosystem and by
      the diversity of possible phenological metrics, which vary in their ecological
      relevance to food web interactions. We compare phenological change for
      phytoplankton (chlorophyll a), zooplankton (Daphnia) and fish (perch, Perca
      fluviatilis) in two basins of Windermere over 40 years and determine whether
      change has differed among trophic levels, while explicitly accounting for among
      metric differences in rates of change. Though rates of change differed markedly
      among the nine metrics used, seasonal events shifted earlier for all metrics and
      trophic levels: zooplankton advanced most, and fish least, rapidly. Evidence of
      altered synchrony was found in both lake basins, when combining information from
      all phenological metrics. However, comparisons based on single metrics did not
      consistently detect this signal. A multimetric approach showed that across
      trophic levels, earlier phenological events have been associated with increasing
      water temperature. However, for phytoplankton and zooplankton, phenological
      change was also associated with changes in resource availability. Lower silicate,
      and higher phosphorus, concentrations were associated with earlier phytoplankton
      growth, and earlier phytoplankton growth was associated with earlier zooplankton
      growth. The developing trophic mismatch detected between the dominant fish
      species in Windermere and important zooplankton food resources may ultimately
      affect fish survival and portend significant impacts upon ecosystem functioning.
      We advocate that future studies on phenological synchrony combine data from
      multiple phenological metrics, to increase confidence in assessments of change
      and likely ecological consequences.

PMID- 23868352
TI  - CT, MRI and laparoscopy findings of a retroperitoneally herniated ovary causing
      acute abdominal pain.
AB  - We report a case of a young woman presenting with abdominal pain due to a rare
      and recurrent herniation of the ovary, to a retroperitoneal location lateral to
      the external iliac artery and directly dorsal to the iliopsoas muscle.
      Correlation between computed tomography, magnetic resonance imaging and
      laparoscopy is presented. The patient's complaints subsided after right
      oophoropexy. When aware, this diagnosis is easy to make and may allow symptomatic
      patients to be treated with laparoscopic oophoropexy. 

PMID- 23868354
TI  - Highly efficient singlet-singlet energy transfer in light-harvesting
      [60,70]fullerene-4-amino-1,8-naphthalimide dyads.
AB  - New C60 and C70 fullerene dyads formed with 4-amino-1,8-naphthalimide
      chromophores have been prepared by the Bingel cyclopropanation reaction. The
      resulting monoadducts were investigated with respect to their fluorescence
      properties (quantum yields and lifetimes) to unravel the role of the charge
      transfer naphthalimide chromophore as a light-absorbing antenna and excited
      singlet-state sensitizer of fullerenes. The underlying intramolecular singlet
      singlet energy transfer (EnT) process was fully characterized and found to
      proceed quantitatively (Phi(EnT)~1) for all dyads. Thus, these conjugates are of
      considerable interest for applications in which fullerene excited states have to
      be created and photonic energy loss should be minimized. In polar solvents
      (tetrahydrofuran and benzonitrile), fluorescence quenching of the fullerene by
      electron transfer from the ground-state aminonaphthalimide was postulated as an
      additional path.

PMID- 23868355
TI  - Different strategies of cadmium detoxification in the submerged macrophyte
      Ceratophyllum demersum L.
AB  - The heavy metal cadmium (Cd) is highly toxic to plants. To understand the
      mechanisms of tolerance and resistance to Cd, we treated the rootless, submerged
      macrophyte Ceratophyllum demersum L. with sub-micromolar concentrations of Cd
      under environmentally relevant conditions. X-ray fluorescence measurements
      revealed changing distribution patterns of Cd and Zn at non-toxic (0.2 nM, 2 nM),
      moderately toxic (20 nM) and highly toxic (200 nM) levels of Cd. Increasing Cd
      concentrations led to enhanced sequestration of Cd into non-photosynthetic
      tissues like epidermis and vein. At toxic Cd concentrations, Zn was redistributed
      and mainly found in the vein. Cd treatment induced the synthesis of
      phytochelatins (PCs) in the plants, with a threshold of induction already at 20
      nM Cd for PC3. In comparison, in plants treated with Cu, elevated PC levels were
      detected only at the highest concentrations (100-200 nM Cu). Our results show
      that also non-accumulators like C. demersum store toxic metals in tissues where
      the heavy metal interferes least with metabolic pathways, but remaining toxicity
      interferes with micronutrient distribution. Furthermore, we found that the
      induction of phytochelatins is not proportional to metal concentration, but has a
      distinct threshold, specific for each PC species. Finally we could show that 20
      nM Cd, which was previously regarded as non-toxic to most plants, already induces
      detoxifying mechanisms. 

PMID- 23868356
TI  - Child routines and parental adjustment as correlates of internalizing and
      externalizing symptoms in children diagnosed with ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) is one of the most common
      disorders of childhood, and the presence of comorbid externalizing and
      internalizing symptoms often result in severe negative long-term consequences.
      Multiple etiological factors contribute to the development of co-occurring
      symptoms. Family stability and consistency appear to be particularly important in
      effectively managing behavioral concerns. One important factor in producing
      consistency and stability is the use of routines. The current study examined how
      routines may be related to internalizing/externalizing symptoms in a clinical
      sample (N = 371) of children with ADHD (M age = 9.13, SD = 1.96; 77% male). After
      controlling for child age, gender, and parental adjustment, routines predicted
      both internalizing and externalizing symptoms. Specific subtypes of routines
      including Household, Discipline, and Homework Routines were found to
      significantly predict symptomatology. A positive relation was found between
      parental and child adjustment problems; however, support for routines moderating
      the relation between parent and child adjustment was not supported.

PMID- 23868357
TI  - Platinum nanopeapods: spatial control of mesopore arrangements by utilizing a
      physically confined space.
AB  - Spherical mesopores: Mesoporous Pt rods containing cage-type mesopores were
      prepared with porous anodic alumina membranes (PAAMs). It is noteworthy that
      spherical mesopores are aligned in the rods due to physical confinement by the
      PAAM channels. Both the mesopore alignment and the morphological control are
      realized simultaneously, which could be important for bottom-up approaches to
      nanometals with desirable structural features (see figure).

PMID- 23868359
TI  - Inclusion body myopathy with Paget disease of the bone and frontotemporal
      dementia associated with a novel G156S mutation in the VCP gene.

PMID- 23868358
TI  - Dilution of protein-surfactant complexes: a fluorescence study.
AB  - Dilution of protein-surfactant complexes is an integrated step in microfluidic
      protein sizing, where the contribution of free micelles to the overall
      fluorescence is reduced by dilution. This process can be further improved by
      establishing an optimum surfactant concentration and quantifying the amount of
      protein based on the fluorescence intensity. To this end, we study the
      interaction of proteins with anionic sodium dodecyl sulfate (SDS) and cationic
      hexadecyl trimethyl ammonium bromide (CTAB) using a hydrophobic fluorescent dye
      (sypro orange). We analyze these interactions fluourometrically with bovine serum
      albumin, carbonic anhydrase, and beta-galactosidase as model proteins. The
      fluorescent signature of protein-surfactant complexes at various dilution points
      shows three distinct regions, surfactant dominant, breakdown, and protein
      dominant region. Based on the dilution behavior of protein-surfactant complexes,
      we propose a fluorescence model to explain the contribution of free and bound
      micelles to the overall fluorescence. Our results show that protein peak is
      observed at 3 mM SDS as the optimum dilution concentration. Furthermore, we study
      the effect of protein concentration on fluorescence intensity. In a single
      protein model with a constant dye quantum yield, the peak height increases with
      protein concentration. Finally, addition of CTAB to the protein-SDS complex at
      mole fractions above 0.1 shifts the protein peak from 3 mM to 4 mM SDS. The
      knowledge of protein-surfactant interactions obtained from these studies provides
      significant insights for novel detection and quantification techniques in
      microfluidics. 

PMID- 23868360
TI  - Evaluations of emamectin benzoate and propiconazole for protecting individual
      Pinus contorta from mortality attributed to colonization by Dendroctonus
      ponderosae and associated fungi.
AB  - BACKGROUND: Protection of conifers from bark beetle colonization typically
      involves applications of liquid formulations of contact insecticides to the tree
      bole. An evaluation was made of the efficacy of bole injections of emamectin
      benzoate alone and combined with the fungicide propiconazole for protecting
      individual lodgepole pine, Pinus contorta Dougl. ex Loud., from mortality
      attributed to colonization by mountain pine beetle, Dendroctonus ponderosae
      Hopkins, and progression of associated blue stain fungi. RESULTS: Injections of
      emamectin benzoate applied in mid-June did not provide adequate levels of tree
      protection; however, injections of emamectin benzoate + propiconazole applied at
      the same time were effective for two field seasons. Injections of emamectin
      benzoate and emamectin benzoate + propiconazole in mid-September provided tree
      protection the following field season, but unfortunately efficacy could not be
      determined during a second field season owing to insufficient levels of tree
      mortality observed in the untreated control, indicative of low D. ponderosae
      populations. CONCLUSION: Previous evaluations of emamectin benzoate for
      protecting P. contorta from mortality attributed to D. ponderosae have failed to
      demonstrate efficacy, which was later attributed to inadequate distribution of
      emamectin benzoate following injections applied several weeks before D.
      ponderosae colonization. The present data indicate that injections of emamectin
      benzoate applied in late summer or early fall will provide adequate levels of
      tree protection the following summer, and that, when emamectin benzoate is
      combined with propiconazole, tree protection is afforded the year that injections
      are implemented.

PMID- 23868362
TI  - Reply: To PMID 22367992.

PMID- 23868363
TI  - The dangers of clinical conviction: an "M&M" of endovascular therapies for
      stroke.

PMID- 23868364
TI  - First volley in the brain race? Europe's human brain project the first to the
      starting line--will U.S. brain initiative catch up?

PMID- 23868366
TI  - Natural killer cell populations and cytotoxic activity in pigs fed mother's milk,
      formula, or formula supplemented with bovine lactoferrin.
AB  - BACKGROUND: Natural killer (NK) cells are components of the innate immune defense
      system, and their levels differ between breast and formula-fed (FF) infants.
      Lactoferrin (Lf) modulates NK cell cytotoxicity ex vivo. We hypothesized that
      dietary bovine Lf (bLf) would increase NK cell populations and cytotoxicity.
      METHODS: Piglets were sow-reared (SR), FF, or 1 g/l bLf-fed (LF) for 21 d. NK
      cells (CD3(-)CD4(-)CD8(+)) in blood (peripheral blood mononuclear cells (PBMCs)),
      spleen, and mesenteric lymph node (MLN) were determined by flow cytometry. PBMC
      NK cells were tested for cytotoxic activity against target K562 cells ex vivo in
      the presence of media (unstimulated), interleukin-2, or bLf. NK cell mRNA
      expression was determined by reverse transcription-quantitative PCR. RESULTS: SR
      and LF piglets had more NK cells in MLN (P = 0.0097) and spleen (P = 0.0980) than
      FF piglets. In PBMCs, SR piglets had more NK cells than FF piglets (P = 0.0072);
      LF piglets were intermediate and not different from FF or SR piglets. NK cell
      intelectin-2 mRNA expression was 2.5-fold higher (P = 0.0095) in LF than SR or FF
      piglets. NK cells in SR piglets exhibited greater (P < 0.0001) cytotoxic activity
      than those in LF or FF piglets, which was supported by greater perforin mRNA
      expression. CONCLUSION: Dietary bLf increased blood NK cell populations and NK Lf
      receptor expression but not NK cell cytotoxicity.

PMID- 23868367
TI  - Simulation of temperature and thermally induced stress of human tooth under CO2
      pulsed laser beams using finite element method.
AB  - The authors report the simulation of temperature distribution and thermally
      induced stresses of human tooth under CO2 pulsed laser beam. A detailed tooth
      structure comprising enamel, dentin, and pulp with realistic shapes and
      thicknesses were considered, and a numerical method of finite element was adopted
      to solve time-dependent bio-heat and stress equations. The realistic boundary
      conditions of constant temperature for those parts embedded in the gingiva and
      heat flux condition for those parts out of the gingiva were applied. The results
      which were achieved as a function of energy density (J/cm(2)) showed when laser
      beam is irradiated downward (from the top of the tooth), the temperature and
      thermal stresses decrease quickly as a function of depth that is a result of
      strong absorption of CO2 beams by enamel. This effect is so influential that one
      can use CO2 beams to remove micrometer layers while underlying tissues,
      especially the pulp, are safe from thermal effects. 

PMID- 23868368
TI  - SNAP-25 regulates spine formation through postsynaptic binding to p140Cap.
AB  - Synaptosomal-associated protein of 25 kDa (SNAP-25) is a member of the Soluble N
      ethylmaleimide-sensitive-factor attachment protein receptors (SNARE) protein
      family, required for exocytosis of synaptic vesicles and regulation of diverse
      ion channels. Here, we show that acute reduction of SNAP-25 expression leads to
      an immature phenotype of dendritic spines that are, consistently, less
      functional. Conversely, over-expression of SNAP-25 results in an increase in the
      density of mature, Postsynaptic Density protein 95 (PSD-95)-positive spines. The
      regulation of spine morphogenesis by SNAP-25 depends on the protein's ability to
      bind both the plasma membrane and the adaptor protein p140Cap, a key protein
      regulating actin cytoskeleton and spine formation. We propose that SNAP-25 allows
      the organization of the molecular apparatus needed for spine formation by
      recruiting and stabilizing p140Cap.

PMID- 23868369
TI  - Possible digoxin toxicity associated with concomitant ciprofloxacin therapy.
AB  - CASE (DESCRIPTION): A 27 year old female with a complex history of congenital
      heart disease, cardiac surgery, heart failure, and arrhythmias was admitted for a
      Pseudomonas aeruginosa sternal wound infection and treated with intravenous
      antibiotics. After discharge and completion of an outpatient course of
      intravenous antibiotics, suppressive antibiotic therapy with ciprofloxacin was
      initiated. She presented to clinic with nausea and anorexia within a few days of
      addition of ciprofloxacin to her current regimen of medications, which included
      digoxin. The digoxin was discontinued, with all other medications remaining the
      same, and the symptoms resolved in 48 h. The dose of digoxin was restarted at 50
      % of the previous dose with no further complications. The proposed cause of the
      nausea and anorexia was digoxin toxicity secondary to a drug-drug interaction
      with ciprofloxacin. CONCLUSION: Patients receiving ciprofloxacin and digoxin
      should be monitored closely for the risk of digoxin toxicity.

PMID- 23868371
TI  - Towards reducing population radiation exposure.

PMID- 23868372
TI  - Structural characteristics and biological performance of silk fibroin nanofiber
      containing microalgae Spirulina extract.
AB  - Silk fibroin (SF) nanofiber scaffold containing microalgae Spirulina extract were
      prepared by electrospinning and the performance and functionality of the scaffold
      were evaluated. The viscosity and conductivity of the dope solution of Spirulina
      containing SF were examined for electrospinability and we found that the
      morphological structure of SF nanofiber is affected by the concentration of
      Spirulina extract added. The platelet adhesion and coagulation time test
      confirmed that the Spirulina containing SF nanofiber scaffold had excellent
      ability to prevent blood clotting or antithrombogenicity that is comparable to
      heparin. Low cytotoxicity and excellent cell adhesion and proliferation were also
      observed for Sprulina containing SF nanofiber scaffold by methylthiazolyldiphenyl
      tetrazolium bromide assay and confocal fluorescence microscope using fibroblast
      and human umbilical vein endothelial cells. Based on these results, we believe SF
      nanofiber scaffold containing Spirulina extract has the potential to be used as
      tissue engineering scaffold that requires high hemocompatibility.

PMID- 23868373
TI  - Neurodegenerative disorder with brain iron accumulation previously known as SENDA
      syndrome now genetically determined.

PMID- 23868374
TI  - Successful percutaneous treatment of a mycotic right coronary to right ventricle
      fistula.

PMID- 23868375
TI  - Betaine supplementation causes increase in carnitine metabolites in the muscle
      and liver of mice fed a high-fat diet as studied by nontargeted LC-MS
      metabolomics approach.
AB  - SCOPE: Betaine (BET) reduces diet-induced liver lipid accumulation, and may
      relieve obesity-related metabolic disturbances. The aim of our study was to
      analyze metabolite alterations after supplementation of BET, polydextrose (PDX, a
      soluble dietary fiber), or their combination (BET PDX) via drinking water to
      C57BL/6J mice fed a high-fat (HF) diet. METHODS AND RESULTS: BET supplementation
      increased BET levels in plasma, muscle, and liver (p < 0.05), and the nontargeted
      LC-MS metabolite profiling revealed an increase in several metabolites in the
      carnitine biosynthesis pathway after BET supplementation both in liver and
      muscle. These included carnitine and acetylcarnitine (1.4-fold, p < 0.05),
      propionylcarnitine and gamma-butyrobetaine (1.5-fold, p < 0.05), and several
      other short-chain acylcarnitines (p < 0.05) in muscle. These changes were
      slightly higher in the BET PDX group. Furthermore, BET reduced the HF diet
      induced accumulation of triglycerides in liver (p < 0.05). The supplementations
      did not attenuate the HF diet induced increase in body weight gain or the
      increase in adipose tissue mass. Instead, the combination of BET and PDX tended
      to increase adiposity. CONCLUSION: Our results suggest that increased
      availability of BET in different tissues, especially in muscle, after BET
      supplementation has an impact on carnitine metabolism, and this could further
      explain the link between BET and lipid metabolism.

PMID- 23868376
TI  - Protein structure in context: the molecular landscape of angiogenesis.
AB  - A team of students, educators, and researchers has developed new materials to
      teach cell signaling within its cellular context. Two nontraditional modalities
      are employed: physical models, to explore the atomic details of several of the
      proteins in the angiogenesis signaling cascade, and illustrations of the proteins
      in their cellular environment, to give an intuitive understanding of the cellular
      context of the pathway. The experiences of the team underscore the use of these
      types of materials as an effective mode for fostering students' understanding of
      the molecular world and the scientific method used to define it.

PMID- 23868377
TI  - Glucose as the sole metabolic fuel: overcoming a misconception using conceptual
      change to teach the energy-yielding metabolism to Brazilian high school students.
AB  - A misconception regarding the human metabolism has been shown to be widespread
      among high school students. The students consider glucose as the sole metabolic
      fuel, disregarding that lipids and amino acids can be oxidized for ATP production
      by human cells. This misconception seems to be a consequence of formal teaching
      in grade and high schools. The present study reports the evaluation of a teaching
      strategy based on the use of a dialogic teaching methodology within a conceptual
      change approach to remediate that misconception. Students were stimulated to
      formulate hypotheses, outline experiments, and to discuss their outcomes. The
      results showed that students were able to reformulate their original concepts
      immediately after teaching. The majority of the students showed adequate learning
      of the topic eight months after the application of the teaching strategy,
      although some level of misconception recurrence was observed. The educational
      consequences of the teaching unit are discussed in the context of the possible
      reasons for its success as well as the need for similar initiatives at grade
      school to avoid the establishment of the misconception.

PMID- 23868378
TI  - Assessment of a novel group-centered testing schema in an upper-level
      undergraduate molecular biotechnology course.
AB  - Providing students with assignments that focus on critical thinking is an
      important part of their scientific and intellectual development. However, as
      class sizes increase, so does the grading burden, prohibiting many faculty from
      incorporating critical thinking assignments in the classroom. In an effort to
      continue to provide our students with meaningful critical thinking exercises, we
      implemented a novel group-centered, problem-based testing scheme. We wanted to
      assess how performing critical thinking problem sets as group work compares to
      performing the sets as individual work, in terms of student attitudes and
      learning outcomes. During two semesters of our recombinant DNA course, students
      had the same lecture material and similar assessments. In the Fall semester,
      student learning was assessed by two collaborative take-home exams, followed
      immediately by individual, closed-book in-class exams on the same content, as
      well as a final cumulative exam. Student teams on the take-home exams were
      instructor-assigned, and each team turned in one collaborative exam. In the
      Spring semester, the control group of students were required to turn in their own
      individual take-home exams, followed by the in-class exams and final cumulative
      exam. For the majority of students, learning outcomes were met, regardless of
      whether they worked in teams. In addition, collaborative learning was favorably
      received by students and grading was reduced for instructors. These data suggest
      that group-centered, problem-based learning is a useful model for achievement of
      student learning outcomes in courses where it would be infeasible to provide
      feedback on individual critical thinking assignments due to grading volume.

PMID- 23868379
TI  - Purification and characterization of enzymes from yeast: an extended
      undergraduate laboratory sequence for large classes.
AB  - Providing a project-based experience in an undergraduate biochemistry laboratory
      class can be complex with large class sizes and limited resources. We have
      designed a 6-week curriculum during which students purify and characterize the
      enzymes invertase and phosphatase from bakers yeast. Purification is performed in
      two stages via ethanol precipitation and anion exchange chromatography, and
      students perform both direct and coupled enzyme assays. By completion of the
      experimental series, students are able to identify which enzymes they have
      purified and have obtained kinetic parameters for one. This experimental series
      requires minimal instructor preparation time, is cost effective, and works with
      multiple sections of large groups of students. Students participating in this
      sequence showed increases in conceptual understanding of biochemical concepts as
      measured through in-class assessments and anonymous surveys.

PMID- 23868380
TI  - Using PCR-RFLP technology to teach single nucleotide polymorphism for
      undergraduates.
AB  - Recent studies indicated that the aberrant gene expression of peroxiredoxin-6
      (prdx6) was found in various kinds of cancers. Because of its biochemical
      function and gene expression pattern in cancer cells, the association between
      genetic polymorphism of Prdx6 and cancer onset is interesting. In this report, we
      have developed and implemented a serial experiment in molecular biology
      laboratory course to teach single nucleotide polymorphism (SNP) to undergraduate
      students majoring in molecular biology or genetics. The flanking sequence of
      rs4382766 was located in Prdx6 gene, which contained a restriction site of SspI,
      and was used as a target in this lab course. The students could mimic real
      research by integrating different techniques, such as database retrieving,
      genomic DNA isolation, PCR, and restriction enzyme assay. This serial experiment
      of PCR-RFLP helps students set up intact idea of molecular biology and understand
      the relation among individual experiments. Students were found to be more
      enthusiastic during the laboratory classes than those in the former curriculum.

PMID- 23868381
TI  - Commentary: what does "student-centered" mean and how can it be implemented? A
      systematic perspective.

PMID- 23868382
TI  - Problem-based test: replication of mitochondrial DNA during the cell cycle.
AB  - Terms to be familiar with before you start to solve the test: cell cycle,
      generation time, S-phase, cell culture synchronization, isotopic pulse-chase
      labeling, density labeling, equilibrium density-gradient centrifugation, buoyant
      density, rate-zonal centrifugation, nucleoside, nucleotide, kinase enzymes,
      polymerization of nucleic acids, re-replication block, cell fractionation,
      Svedberg (sedimentation constant = [ S]), nuclear DNA, mitochondrial DNA, heavy
      and light mitochondrial DNA chains, heteroplasmy, mitochondrial diseases

PMID- 23868383
TI  - Commentary: massive open online courses.

PMID- 23868384
TI  - Reflections on MOOCs after taking three courses: strengths and weaknesses.

PMID- 23868387
TI  - Gastroprotective, cytoprotective and antioxidant effects of Oleum cinnamomi on
      ethanol induced damage.
AB  - Peptic ulcer disease is a gastrointestinal disorder defined by mucosal damage and
      free oxygen radicals associated with peptic ulcer and gastritis. Cinnamon is a
      traditional herb used for many diseases and it has also effects as an
      antioxidant, anti-inflammatory, antispasmodic and anti-ulcerative. Our research
      is based on oxidative stress and effects of Oleum cinnamomi on stomach, liver and
      kidney disorders induced by ethanol. In our experiment, 2-3 month old male
      Sprague-Dawley rats were used. One hour before the mucosal damage induced by 70 %
      ethanol, O. cinnamomi (2.5 ml/kg) was added into the groups. Gastric pH, analysis
      of gastric mucus and ulcer index were calculated from samples obtained from the
      stomach. Superoxide dismutase (SOD), malondialdehyde and catalase (CAT) levels
      were determined in stomach, liver and kidney homogenates and erythrocyte
      hemolysate. Histopathological examination of stomach, liver and kidney were
      determined with H&E staining. The non-treated ulcerative group showed higher
      scores than the control group which was treated with O. cinnamomi, when ulcer
      scores, gastric mucus and pH level of stomach are compared. Increased lipid
      peroxidation levels were observed in the liver, kidney and erythrocyte
      hemolysate. SOD activity was decreased in liver whereas increased in stomach of
      ethanol treated ulcerative groups. CAT levels were increased in stomach and liver
      of ethanol treated rats. Histopathological findings showed that ethanol treatment
      cause multiply organ damage such as stomach, liver and kidney injury. O.
      cinnamomi treatment protected these tissues from ethanol-induced damage.
      Consequently, the current investigation shows that O. cinnamomi has protective
      effects on ethanol-induced oxidative and mucosal damage. 

PMID- 23868388
TI  - Recombinant proteins produced into yolk of genetically manipulated chickens are
      partly sialylated in N-glycan.
AB  - The transgenic chicken is a candidate for the production of biopharmaceutical
      proteins with several economic superiorities. In general, the addition of sialic
      acid at the terminal of N-glycan is important for the bioactivity of
      biopharmaceuticals including plasma half-life; however, sialic acid has not been
      detected in the N-glycan of proteins produced in the egg white of genetically
      manipulated chickens. In this study, the extracellular domain of the TNF receptor
      and single chain Fv fused to Fc (referred to as TNFR/Fc and scFv/Fc,
      respectively) were purified from the egg yolk of genetically manipulated chickens
      and their sialylation in N-glycan was examined. In contrast to the glycan in egg
      white, yolk-derived proteins were partly sialylated. Lectin blot showed the
      existence of alpha2,6-sialic acid on TNFR/Fc, which disappeared with the removal
      of N-glycan by PNGase. In scFv/Fc, up to 7 % of N-glycan contained sialic acid.
      Disialyl glycans, which were detected in serum-derived scFv/Fc in a previous
      study, were not found in the yolk sample. Ovarian follicular tissue, which
      surrounds growing yolk, expressed several neuraminidases, suggesting the partial
      truncation of glycan during the yolk transfer process from the blood. 

PMID- 23868389
TI  - Evaluation of the sensory characteristics of strawberry cultivars throughout the
      harvest season using projective mapping.
AB  - BACKGROUND: Strawberry breeding programs should be able to rely on valid and
      simple methodologies for evaluating sensory quality of new cultivars. In this
      context, the aim of the present work was to evaluate the applicability of a
      simple sensory methodology, named projective mapping, to evaluate the sensory
      characteristics of strawberry cultivars and advanced selections throughout the
      harvest season. Three strawberry cultivars and two advanced selections were
      evaluated by an untrained assessor panel using projective mapping in three
      different moments of the harvest season: June (early season), August (mid-season)
      and September (peak harvest). Instrumental measurements were also performed.
      RESULTS: Projective mapping enabled the identification of the main sensory
      characteristics of the strawberry cultivars and advanced selections, as well as
      the similarities and differences among them. Sensory characteristics of the five
      evaluated strawberry cultivars and advanced selections largely varied throughout
      the harvest season. Simple instrumental measurements were not able to predict the
      sensory characteristics of the strawberry cultivars, suggesting the importance of
      sensory methodologies for the evaluation of new cultivars in breeding programs.
      CONCLUSIONS: Projective mapping consisted of a quick alternative for the
      evaluation of new cultivars relative to standard commercial cultivars. Its main
      advantage is that a large number of cultivars can be screened with minimal
      investment of time and resources.

PMID- 23868390
TI  - Nanoprobe arrays for multiple single cell insertion using heterogeneous
      nanosphere lithography (HNSL).
AB  - Nanoprobe arrays for multiple single cell insertion were developed using
      heterogeneous nanosphere lithography. Using two heterogeneous nanoparticles as
      sacrificial and masking particles, high aspect ratio Si nanoprobes were
      fabricated in an array with spacing between the nanoprobes ranging from a few to
      tens of micrometers. For registered single cell analysis, multiple and precise
      insertion of nanoprobes into multiple single cells in a parallel fashion was
      demonstrated using micropipette suction and micromanipulators. 

PMID- 23868391
TI  - Solution structure of the N-terminal domain of a replication restart primosome
      factor, PriC, in Escherichia coli.
AB  - In eubacterial organisms, the oriC-independent primosome plays an essential role
      in replication restart after the dissociation of the replication DNA-protein
      complex by DNA damage. PriC is a key protein component in the replication restart
      primosome. Our recent study suggested that PriC is divided into two domains: an N
      terminal and a C-terminal domain. In the present study, we determined the
      solution structure of the N-terminal domain, whose structure and function have
      remained unknown until now. The revealed structure was composed of three helices
      and one extended loop. We also observed chemical shift changes in the
      heteronuclear NMR spectrum and oligomerization in the presence of ssDNA. These
      abilities may contribute to the PriC-ssDNA complex, which is important for the
      replication restart primosome. 

PMID- 23868392
TI  - Responses of CO(2), N(2)O and CH(4) fluxes between atmosphere and forest soil to
      changes in multiple environmental conditions.
AB  - To investigate the effects of multiple environmental conditions on greenhouse gas
      (CO2 , N2 O, CH4 ) fluxes, we transferred three soil monoliths from Masson pine
      forest (PF) or coniferous and broadleaved mixed forest (MF) at Jigongshan to
      corresponding forest type at Dinghushan. Greenhouse gas fluxes at the in situ
      (Jigongshan), transported and ambient (Dinghushan) soil monoliths were measured
      using static chambers. When the transported soil monoliths experienced the
      external environmental factors (temperature, precipitation and nitrogen
      deposition) at Dinghushan, its annual soil CO2 emissions were 54% in PF and 60%
      in MF higher than those from the respective in situ treatment. Annual soil N2 O
      emissions were 45% in PF and 44% in MF higher than those from the respective in
      situ treatment. There were no significant differences in annual soil CO2 or N2 O
      emissions between the transported and ambient treatments. However, annual CH4
      uptake by the transported soil monoliths in PF or MF was not significantly
      different from that at the respective in situ treatment, and was significantly
      lower than that at the respective ambient treatment. Therefore, external
      environmental factors were the major drivers of soil CO2 and N2 O emissions,
      while soil was the dominant controller of soil CH4 uptake. We further tested the
      results by developing simple empirical models using the observed fluxes of CO2
      and N2 O from the in situ treatment and found that the empirical models can
      explain about 90% for CO2 and 40% for N2 O of the observed variations at the
      transported treatment. Results from this study suggest that the different
      responses of soil CO2 , N2 O, CH4 fluxes to changes in multiple environmental
      conditions need to be considered in global change study. 

PMID- 23868393
TI  - Unusual Stepwise Protonation and J-Aggregation of meso-Tetrakis(N
      methylpyridinium-4-yl)porphine on Binding Poly(sodium vinylsulfonate).
AB  - The binding of a tetracationic porphyrin to a highly charged polymer like
      poly(sodium vinylsulfonate) has been investigated over a wide pH range and under
      various experimental conditions. We present evidence that, depending on the pH,
      the high electrostatic field exerted by the polymer stabilizes the diprotonated
      form of the free base porphyrin at unusual pH values or otherwise causes the
      formation of H-type aggregates. In particular, at a low polymer concentration,
      lowering the pH at first allows the formation of the diacid species then it
      determines its reorganization in close-packed J-type aggregates. The employment
      of various metallo-derivatives of the title porphyrin enables a better insight
      into the nature of all the detected species. 

PMID- 23868394
TI  - Relevance of roughness parameters of surface finish in precision hard turning.
AB  - Precision hard turning is a process to improve the surface integrity of
      functional surfaces. Machining experiments are carried out on hardened AISI 52100
      bearing steel under dry condition using c-BN cutting tools. A full factorial
      experimental design is used to characterize the effect of cutting parameters. As
      surface topography is characterized by numerous roughness parameters, their
      relative relevance is investigated by statistical indices of performance computed
      by combining the analysis of variance, discriminant analysis and the bootstrap
      method. The analysis shows that the profile Length ratio (Lr) and the Roughness
      average (Ra) are the relevant pair of roughness parameters which best
      discriminates the effect of cutting parameters and enable the classification of
      surfaces which cannot be distinguished by one parameter: low profile length ratio
      Lr (Lr = 100.23%) is clearly distinguished from an irregular surface
      corresponding to a profile length ratio Lr (Lr = 100.42%), whereas the roughness
      average Ra values are nearly identical.

PMID- 23868395
TI  - You don't really love me, do you? Negative effects of imagine-other perspective
      taking on lower self-esteem individuals' relationship well-being.
AB  - Two studies demonstrated that active efforts to appreciate a romantic partner's
      unique point of view (imagine-other perspective-taking) lead individuals lower in
      self-esteem (LSEs) to feel less loved by their partner and less satisfied with
      their relationship as a result. These effects were evident regardless of whether
      individuals' perspective-taking efforts involved reflecting specifically on a
      disagreement with their partner (Study 2) or not (Study 1). The studies thus
      identify a new path through which perspective-taking efforts can detract from
      relational well-being, one to which LSEs are uniquely vulnerable. Results from an
      open-ended thought-listing task administered in Study 2 confirmed that increased
      cognitive energy LSEs devoted to drawing (negative) metaperceptual inferences
      about their partner's evaluation of them contributed to the negative effect of
      imagine-other perspective-taking on their perceived regard. No such effects were
      evident for individuals higher in self-esteem, and imagine-self perspective
      taking instead exerted a general positive influence on individuals' evaluations
      of their partner. 

PMID- 23868396
TI  - Key health themes and reporting of numerical cigarette-waterpipe equivalence in
      online news articles reporting on waterpipe tobacco smoking: a content analysis.
AB  - INTRODUCTION: There is anecdotal evidence that health messages interpreted from
      waterpipe tobacco smoking (WTS) research are inconsistent, such as comparing the
      health effects of one WTS session with that of 100 cigarettes. This study aimed
      to identify key health themes about WTS discussed by online news media, and how
      numerical cigarette-waterpipe equivalence (CWE) was being interpreted. METHODS:
      We identified 1065 online news articles published between March 2011 and
      September 2012 using the 'Google Alerts' service. We screened for health themes,
      assessed statements mentioning CWE and reported differences between countries. We
      used logistic regression to identify factors associated with articles incorrectly
      reporting a CWE equal to or greater than 100 cigarettes, in the absence of any
      comparative parameter ('CWE >=100 cigarettes'). RESULTS: Commonly mentioned
      health themes were the presence of tobacco (67%) and being as bad as cigarettes
      (49%), and we report on differences between countries. While 10.8% of all news
      articles contained at least one positive health theme, 22.9% contained a
      statement about a CWE. Most of these (18.6% total) were incorrectly a CWE >=100
      cigarettes, a quarter of which were made by healthcare
      professionals/organisations. Compared with the Middle East, articles from the USA
      and the UK were the most significant predictors to contain a CWE >=100 cigarettes
      statement. CONCLUSIONS: Those wishing to write or publish information related to
      WTS may wish to avoid comparing WTS to cigarettes using numerical values as this
      is a major source of confusion. Future research is needed to address the impact
      of the media on the attitudes, initiation and cessation rates of waterpipe
      smokers.

PMID- 23868397
TI  - Left-digit price effects on smoking cessation motivation.
AB  - BACKGROUND: Cigarette price increases have been associated with increases in
      smoking cessation, but relatively little is known about this relationship at the
      level of individual smokers. To address this and to inform tax policy, the goal
      of this study was to apply a behavioural economic approach to the relationship
      between the price of cigarettes and the probability of attempting smoking
      cessation. METHODS: Adult daily smokers (n=1074; ie, 5+ cigarettes/day; 18+ years
      old; >=8th grade education) completed in-person descriptive survey assessments.
      Assessments included estimated probability of making a smoking cessation attempt
      across a range of cigarette prices, demographics and nicotine dependence.
      RESULTS: As price increases, probability of making a smoking cessation attempt
      exhibited an orderly increase, with the form of the relationship being similar to
      an inverted demand curve. The largest effect size increases in motivation to make
      a quit attempt were in the form of 'left-digit effects,' (ie, maximal sensitivity
      across pack price whole-number changes; eg, US$5.80-6/pack). Significant
      differences were also observed among the left-digit effects, suggesting the most
      substantial effects were for price changes that were most market relevant.
      Severity of nicotine dependence was significantly associated with price
      sensitivity, but not for all indices. CONCLUSIONS: These data reveal the clear
      and robust relationship between the price of cigarettes and an individual's
      motivation to attempt smoking cessation. Furthermore, the current study indicates
      the importance of left-digit price transitions in this relationship, suggesting
      policymakers should consider relative price positions in the context of tax
      changes.

PMID- 23868398
TI  - Persistent ischemic stroke disparities despite declining incidence in Mexican
      Americans.
AB  - OBJECTIVE: To determine trends in ischemic stroke incidence among Mexican
      Americans and non-Hispanic whites. METHODS: We performed population-based stroke
      surveillance from January 1, 2000 to December 31, 2010 in Corpus Christi, Texas.
      Ischemic stroke patients 45 years and older were ascertained from potential
      sources, and charts were abstracted. Neurologists validated cases based on source
      documentation blinded to ethnicity and age. Crude and age-, sex-, and ethnicity
      adjusted annual incidence was calculated for first ever completed ischemic
      stroke. Poisson regression models were used to calculate adjusted ischemic stroke
      rates, rate ratios, and trends. RESULTS: There were 2,604 ischemic strokes in
      Mexican Americans and 2,042 in non-Hispanic whites. The rate ratios (Mexican
      American:non-Hispanic white) were 1.94 (95% confidence interval [CI] = 1.67
      2.25), 1.50 (95% CI = 1.35-1.67), and 1.00 (95% CI = 0.90-1.11) among those aged
      45 to 59, 60 to 74, and 75 years and older, respectively, and 1.34 (95% CI = 1.23
      1.46) when adjusted for age. Ischemic stroke incidence declined during the study
      period by 35.9% (95% CI = 25.9-44.5). The decline was limited to those aged >=60
      years, and happened in both ethnic groups similarly (p > 0.10), implying that the
      disparities seen in the 45- to 74-year age group persist unabated.
      INTERPRETATION: Ischemic stroke incidence rates have declined dramatically in the
      past decade in both ethnic groups for those aged >=60 years. However, the
      disparity between Mexican American and non-Hispanic white stroke rates persists
      in those <75 years of age. Although the decline in stroke is encouraging,
      additional prevention efforts targeting young Mexican Americans are warranted.

PMID- 23868399
TI  - Distinct iron isotopic signatures and supply from marine sediment dissolution.
AB  - Oceanic iron inputs must be traced and quantified to learn how they affect
      primary productivity and climate. Chemical reduction of iron in continental
      margin sediments provides a substantial dissolved flux to the oceans, which is
      isotopically lighter than the crust, and so may be distinguished in seawater from
      other sources, such as wind-blown dust. However, heavy iron isotopes measured in
      seawater have recently led to the proposition of another source of dissolved iron
      from 'non-reductive' dissolution of continental margins. Here we present the
      first pore water iron isotope data from a passive-tectonic and semi-arid ocean
      margin (South Africa), which reveals a smaller and isotopically heavier flux of
      dissolved iron to seawater than active-tectonic and dysoxic continental margins.
      These data provide in situ evidence of non-reductive iron dissolution from a
      continental margin, and further show that geological and hydro-climatic factors
      may affect the amount and isotopic composition of iron entering the ocean. 

PMID- 23868400
TI  - Electronic structure of the Mn-cofactor of modified bacterial reaction centers
      measured by electron paramagnetic resonance and electron spin echo envelope
      modulation spectroscopies.
AB  - The electronic structure of a Mn(II) ion bound to highly oxidizing reaction
      centers of Rhodobacter sphaeroides was studied in a mutant modified to possess a
      metal binding site at a location comparable to the Mn4Ca cluster of photosystem
      II. The Mn-binding site of the previously described mutant, M2, contains three
      carboxylates and one His at the binding site (Thielges et al., Biochemistry
      44:389-7394, 2005). The redox-active Mn-cofactor was characterized using electron
      paramagnetic resonance (EPR) and electron spin echo envelope modulation (ESEEM)
      spectroscopies. In the light without bound metal, the Mn-binding mutants showed
      an EPR spectrum characteristic of the oxidized bacteriochlorophyll dimer and
      reduced quinone whose intensity was significantly reduced due to the diminished
      quantum yield of charge separation in the mutant compared to wild type. In the
      presence of the metal and in the dark, the EPR spectrum measured at the X-band
      frequency of 9.4 GHz showed a distinctive spin 5/2 Mn(II) signal consisting of 16
      lines associated with both allowed and forbidden transitions. Upon illumination,
      the amplitude of the spectrum is decreased by over 80 % due to oxidation of the
      metal upon electron transfer to the oxidized bacteriochlorophyll dimer. The EPR
      spectrum of the Mn-cofactor was also measured at the Q-band frequency of 34 GHz
      and was better resolved as the signal was composed of the six allowed electronic
      transitions with only minor contributions from other transitions. A fit of the Q
      band EPR spectrum shows that the Mn-cofactor is a high spin Mn(II) species (S =
      5/2) that is six-coordinated with an isotropic g-value of 2.0006, a weak zero
      field splitting and E/D ratio of approximately 1/3. The ESEEM experiments showed
      the presence of one (14)N coordinating the Mn-cofactor. The nitrogen atom is
      assigned to a His by comparing our ESEEM results to those previously reported for
      Mn(II) ions bound to other proteins and on the basis of the X-ray structure of
      the M2 mutant that shows the presence of only one His, residue M193, that can
      coordinate the Mn-cofactor. Together, the data allow the electronic structure and
      coordination environment of the designed Mn-cofactor in the modified reaction
      centers to be characterized in detail and compared to those observed in other
      proteins with Mn-cofactors.

PMID- 23868402
TI  - A new theoretical method for calculating the radiative association cross section
      of a triatomic molecule: application to N2-H-.
AB  - We present a new theoretical method to treat the atom-diatom radiative
      association within a time independent approach. This method is an adaptation of
      the driven equations method developed for photodissociation. The bound state
      energies and wave functions of the molecule are calculated exactly and used to
      propagate the overlap with the initial scattering wave function. In the second
      part of this paper, this approach is applied to the radiative association of the
      N2H(-) anion. The main features of the radiative association cross sections are
      analysed and the magnitude of the calculated rate coefficient at 10 K is used to
      discuss the existence of the N2H(-) in the interstellar medium which could be
      used as a tracer of both N2 and H(-). 

PMID- 23868401
TI  - Metabolic potential of lithifying cyanobacteria-dominated thrombolitic mats.
AB  - Thrombolites are unlaminated carbonate deposits formed by the metabolic
      activities of microbial mats and can serve as potential models for understanding
      the molecular mechanisms underlying the formation of lithifying communities. To
      assess the metabolic complexity of these ecosystems, high throughput DNA
      sequencing of a thrombolitic mat metagenome was coupled with phenotypic
      microarray analysis. Functional protein analysis of the thrombolite community
      metagenome delineated several of the major metabolic pathways that influence
      carbonate mineralization including cyanobacterial photosynthesis, sulfate
      reduction, sulfide oxidation, and aerobic heterotrophy. Spatial profiling of
      metabolite utilization within the thrombolite-forming microbial mats suggested
      that the top 5 mm contained a more metabolically diverse and active community
      than the deeper within the mat. This study provides evidence that despite the
      lack of mineral layering within the clotted thrombolite structure there is a
      vertical gradient of metabolic activity within the thrombolitic mat community.
      This metagenomic profiling also serves as a foundation for examining the active
      role individual functional groups of microbes play in coordinating metabolisms
      that lead to mineralization. 

PMID- 23868403
TI  - Endoscopic submucosal dissection for early gastric cancer in anastomosis site
      after distal gastrectomy.
AB  - BACKGROUND: Detection of early gastric cancer (EGC) in the remnant stomach is
      increasing because of follow-up endoscopic surveillance programs. Endoscopic
      treatment appears to be desirable for EGC in the remnant stomach because it is
      less invasive than surgical resection. METHODS: In this retrospective study, to
      evaluate the feasibility of endoscopic submucosal dissection (ESD) for EGC in an
      anastomotic site, treatment results of ESD for EGC in an anastomotic site and in
      remnant stomach not involving an anastomotic site were compared. In total, 11 EGC
      lesions of anastomotic sites in 11 patients and 22 EGC lesions of remnant stomach
      not involving an anastomotic site in 21 patients were treated by ESD. RESULTS:
      All lesions were successfully treated by en bloc resection. There were three
      patients with perforations in the anastomotic site group. Although resected
      specimen size and tumor size were larger in the anastomotic site group than in
      the non-anastomotic site group (P < 0.01), the procedure duration was far longer
      in the anastomotic site group than in the non-anastomotic site group (P < 0.01).
      The speed of the procedure was faster in the non-anastomotic site group than in
      the anastomotic site group (P < 0.05). CONCLUSIONS: Although ESD for EGC in an
      anastomotic site is a time-consuming procedure and requires advanced techniques
      compared with ESD for EGC not involving an anastomotic site, a high en bloc
      resection rate was achieved. ESD by endoscopists with sufficient experience
      appears to be a feasible treatment for EGC in an anastomotic site.

PMID- 23868404
TI  - Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid
      on liver lymphocytes in mice.
AB  - Although ursodeoxycholic acid (UDCA) has long been used for patients with chronic
      cholestatic liver diseases, particularly primary biliary cirrhosis, it may
      modulate the host immune response. This study investigated the effect of UDCA
      feeding on experimental hepatitis, endotoxin shock, and bacterial infection in
      mice. C57BL/6 mice were fed a diet supplemented with or without 0.3% (wt/vol)
      UDCA for 4 wk. UDCA improved hepatocyte injury and survival in concanavalin-A
      (Con-A)-induced hepatitis by suppressing IFN-gamma production by liver
      mononuclear cells (MNC), especially NK and NKT cells. UDCA also increased
      survival after lipopolysaccharide (LPS)-challenge; however, it increased
      mortality of mice following Escherichia coli infection due to the worsening of
      infection. UDCA-fed mice showed suppressed serum IL-18 levels and production of
      IL-18 from liver Kupffer cells, which together with IL-12 potently induce IFN
      gamma production. However, unlike normal mice, exogenous IL-18 pretreatment did
      not increase the serum IFN-gamma levels after E. coli, LPS, or Con-A challenge in
      the UDCA-fed mice. Interestingly, however, glucocorticoid receptor (GR)
      expression was significantly upregulated in the liver MNC of the UDCA-fed mice
      but not in their whole liver tissue homogenates. Silencing GR in the liver MNC
      abrogated the suppressive effect of UDCA on LPS- or Con-A-induced IFN-gamma
      production. Furthermore, RU486, a GR antagonist, restored the serum IFN-gamma
      level in UDCA-fed mice after E. coli, LPS, or Con-A challenge. Taken together,
      these results suggest that IFN-gamma-reducing immunomodulatory property of UDCA
      is mediated by elevated GR in the liver lymphocytes in an IL-12/18-independent
      manner.

PMID- 23868406
TI  - Advanced glycation end products promote hepatosteatosis by interfering with SCAP
      SREBP pathway in fructose-drinking mice.
AB  - Clinical studies have linked the increased consumption of fructose to the
      development of obesity, dyslipidemia, and impaired glucose tolerance, and a role
      in hepatosteatosis development is presumed. Fructose can undergo a nonenzymatic
      reaction from which advanced glycation end products (AGEs) are derived, leading
      to the formation of dysfunctional, fructosylated proteins; however, the in vivo
      formation of AGEs from fructose is still less known than that from glucose. In
      the present study C57Bl/6J mice received 15% (wt/vol) fructose (FRT) or 15%
      (wt/vol) glucose (GLC) in water to drink for 30 wk, resembling human habit to
      consume sugary drinks. At the end of the protocol both FRT- and GLC-drinking mice
      had increased fasting glycemia, glucose intolerance, altered plasma lipid
      profile, and marked hepatosteatosis. FRT mice had higher hepatic triglycerides
      deposition than GLC, paralleled by a greater increased expression and activity of
      the sterol regulatory element-binding protein 1 (SREBP1), the transcription
      factor responsible for the de novo lipogenesis, and of its activating protein
      SCAP. LC-MS analysis showed a different pattern of AGE production in liver tissue
      between FRT and GLC mice, with larger amount of carboxymethyl lysine (CML)
      generated by fructose. Double immunofluorescence and coimmunoprecipitation
      analysis revealed an interaction between CML and SCAP that could lead to
      prolonged activation of SREBP1. Overall, the high levels of CML and activation of
      SCAP/SREBP pathway associated to high fructose exposure here reported may suggest
      a key role of this signaling pathway in mediating fructose-induced lipogenesis.

PMID- 23868405
TI  - Tumor protein D52 controls trafficking of an apical endolysosomal secretory
      pathway in pancreatic acinar cells.
AB  - Zymogen granule (ZG) formation in acinar cells involves zymogen cargo sorting
      from trans-Golgi into immature secretory granules (ISGs). ISG maturation
      progresses by removal of lysosomal membrane and select content proteins, which
      enter endosomal intermediates prior to their apical exocytosis. Constitutive and
      stimulated secretion through this mechanism is termed the constitutive-like and
      minor-regulated pathways, respectively. However, the molecular components that
      control membrane trafficking within these endosomal compartments are largely
      unknown. We show that tumor protein D52 is highly expressed in endosomal
      compartments following pancreatic acinar cell stimulation and regulates apical
      exocytosis of an apically directed endolysosomal compartment. Secretion from the
      endolysosomal compartment was detected by cell-surface antigen labeling of
      lysosome-associated membrane protein LAMP1, which is absent from ZGs, and had
      incomplete overlap with surface labeling of synaptotagmin 1, a marker of ZG
      exocytosis. Although culturing (16-18 h) of isolated acinar cells is accompanied
      by a loss of secretory responsiveness, the levels of SNARE proteins necessary for
      ZG exocytosis were preserved. However, levels of endolysosomal proteins D52,
      EEA1, Rab5, and LAMP1 markedly decreased with culture. When D52 levels were
      restored by adenoviral delivery, the levels of these regulatory proteins and
      secretion of both LAMP1 (endolysosomal) and amylase was strongly enhanced. These
      secretory effects were absent in alanine and aspartate substitutions of serine
      136, the major D52 phosphorylation site, and were inhibited by brefeldin A, which
      does not directly affect the ZG compartment. Our results indicate that D52
      directly regulates apical endolysosomal secretion and are consistent with
      previous studies, suggesting that this pathway indirectly regulates ZG secretion
      of digestive enzymes.

PMID- 23868407
TI  - Laxative treatment with polyethylene glycol decreases microbial primary bile salt
      dehydroxylation and lipid metabolism in the intestine of rats.
AB  - Polyethylene glycol (PEG) is a frequently used osmotic laxative that accelerates
      gastrointestinal transit. It has remained unclear, however, whether PEG affects
      intestinal functions. We aimed to determine the effect of PEG treatment on
      intestinal sterol metabolism. Rats were treated with PEG in drinking water (7%)
      for 2 wk or left untreated (controls). We studied the enterohepatic circulation
      of the major bile salt (BS) cholate with a plasma stable isotope dilution
      technique and determined BS profiles and concentrations in bile, intestinal lumen
      contents, and feces. We determined the fecal excretion of cholesterol plus its
      intestinally formed metabolites. Finally, we determined the cytolytic activity of
      fecal water (a surrogate marker of colorectal cancer risk) and the amount and
      composition of fecal microbiota. Compared with control rats, PEG treatment
      increased the pool size (+51%; P < 0.01) and decreased the fractional turnover of
      cholate (-32%; P < 0.01). PEG did not affect the cholate synthesis rate,
      corresponding with an unaffected fecal primary BS excretion. PEG reduced fecal
      excretion of secondary BS and of cholesterol metabolites (each P < 0.01). PEG
      decreased the cytolytic activity of fecal water [54 (46-62) vs. 87 (85-92)%
      erythrocyte potassium release in PEG-treated and control rats, respectively; P <
      0.01]. PEG treatment increased the contribution of Verrucomicrobia (P < 0.01) and
      decreased that of Firmicutes (P < 0.01) in fecal flora. We concluded that PEG
      treatment changes the intestinal bacterial composition, decreases the bacterial
      dehydroxylation of primary BS and the metabolism of cholesterol, and increases
      the pool size of the primary BS cholate in rats.

PMID- 23868409
TI  - Reduced thoracic fluid content in early-stage primary biliary cirrhosis that
      associates with impaired cardiac inotropy.
AB  - Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by
      cholestasis. Recent MRI studies have confirmed the presence of cardiac
      abnormalities in noncirrhotic PBC patients. However, cardiorespiratory
      consequences of these abnormalities have not been explored. Thoracic fluid
      content (TFC) is a noninvasive bioelectrical impedance measure of the electrical
      conductivity of the chest cavity. We explored TFC and its relationship with
      cardiac contractility parameters in early-stage PBC patients, compared with
      chronic liver disease and community controls. TFC was measured in early-stage PBC
      (noncirrhotic; n = 78), nonalcoholic fatty liver disease (n = 23), and primary
      sclerosing cholangitis (n = 18) and in a community control population (n = 78).
      Myocardial contractility was measured as index of contractility, acceleration
      index, cardiac index, stroke index, left ventricular ejection time, and left
      ventricular work index. We also measured total arterial compliance and the
      Heather Index (HI; cardiac inotropy). The PBC group had significantly lower TFC
      compared with controls and the chronic liver disease groups (P < 0.0001). There
      was an association between increasing TFC and markers of cardiac function
      (cardiac index, stroke index, end-diastolic index, index of contractility, and
      acceleration index), together with indicators of cardiac inotropy and total
      arterial compliance. Multivariate analysis confirmed that the only parameter that
      independently associated with TFC was the marker of cardiac inotropy HI (P =
      0.037; beta 0.5). This study has confirmed that TFC is reduced in those with PBC,
      that this is specific to PBC, and that it associates independently with markers
      of cardiac inotropy.

PMID- 23868408
TI  - Characterization of CFTR High Expresser cells in the intestine.
AB  - The CFTR High Expresser (CHE) cells express eightfold higher levels of the cystic
      fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel compared with
      neighboring enterocytes and were first identified by our laboratory (Ameen et
      al., Gastroenterology 108: 1016, 1995). We used double-label immunofluorescence
      microscopy to further study these enigmatic epithelial cells in rat intestine in
      vivo or ex vivo. CHE cells were found in duodenum, most frequent in proximal
      jejunum, and absent in ileum and colon. CFTR abundance increased in CHE cells
      along the crypt-villus axis. The basolateral Na(+)K(+)Cl(-) cotransporter NKCC1,
      a key transporter involved in Cl(-) secretion, was detected at similar levels in
      CHE cells and neighboring enterocytes at steady state. Microvilli appeared
      shorter in CHE cells, with low levels of Myosin 1a, a villus enterocyte-specific
      motor that retains sucrase/isomaltase in the brush-border membrane (BBM). CHE
      cells lacked alkaline phosphatase and absorptive villus enterocyte BBM proteins,
      including Na(+)H(+) exchanger NHE3, Cl(-)/HCO3(-) exchanger SLC26A6 (putative
      anion exchanger 1), and sucrase/isomaltase. High levels of the vacuolar-ATPase
      proton pump were observed in the apical domain of CHE cells. Levels of the NHE
      regulatory factor NHERF1, Na-K-ATPase, and Syntaxin 3 were similar to that of
      neighboring enterocytes. cAMP or acetylcholine stimulation robustly increased
      apical CFTR and basolateral NKCC1 disproportionately in CHE cells relative to
      neighboring enterocytes. These data strongly argue for a specialized role of CHE
      cells in Cl(-)-mediated "high-volume" fluid secretion on the villi of the
      proximal small intestine.

PMID- 23868410
TI  - Hydrogen sulfide-based therapeutics and gastrointestinal diseases: translating
      physiology to treatments.
AB  - Hydrogen sulfide (H2S) is a gaseous meditator that has various physiological and
      pathophysiological roles in the body. It has been shown to be an important
      mediator of gastrointestinal (GI) mucosal defense and contributes significantly
      to repair of damage and resolution of inflammation. Synthesis of H2S increases
      markedly after mucosal injury, and inhibition of H2S in such circumstances leads
      to delayed healing and exacerbated inflammation. The beneficial effects of H2S
      may be attributable to its ability to elevate mucosal blood flow, prevent
      leukocyte-endothelial adhesion, reduce oxidative stress, and stimulate
      angiogenesis. The use of H2S-donating agents and inhibitors of the key enzymes
      contributing to H2S synthesis have provided strong evidence for the importance of
      H2S in enhancing mucosal resistance to damage, as well as modulating inflammation
      and repair. In recent years, significant evidence has been generated to support
      the notion that these positive aspects of H2S can be exploited in drug design,
      particularly for arthritis, inflammatory bowel disease, and colon cancer
      chemoprevention. Thus novel H2S-based therapies have been shown to be effective
      anti-inflammatories that can promote the resolution of inflammation and
      accelerate the healing of GI ulcers. Encouraging results have already been seen
      experimentally with a mesalamine derivative and with H2S-releasing derivatives of
      nonsteroidal anti-inflammatory drugs.

PMID- 23868411
TI  - Extracellular matrix composition significantly influences pancreatic stellate
      cell gene expression pattern: role of transgelin in PSC function.
AB  - Activated pancreatic stellate cells (PSCs) are responsible for the fibrotic
      matrix of chronic pancreatitis and pancreatic cancer. In vitro protocols
      examining PSC biology have usually involved PSCs cultured on plastic, a
      nonphysiological surface. However, PSCs cultured on physiological matrices, e.g.,
      Matrigel (normal basement membrane) and collagen (fibrotic pancreas), may have
      distinctly different behaviors compared with cells cultured on plastic.
      Therefore, we aimed to 1) compare PSC gene expression after culture on plastic,
      Matrigel, and collagen I; 2) validate the gene array data for transgelin, the
      most highly dysregulated gene in PSCs grown on activating vs. nonactivating
      matrices, at mRNA and protein levels; 3) examine the role of transgelin in PSC
      function; and 4) assess transgelin expression in human chronic pancreatitis
      sections. Culture of PSCs on different matrices significantly affected their gene
      expression pattern. 146, 619, and 432 genes, respectively, were differentially
      expressed (P < 0.001) in PSCs cultured on collagen I vs. Matrigel, Matrigel vs.
      plastic, and collagen I vs. plastic. The highest fold change (12.5-fold
      upregulation) in gene expression in cells on collagen I vs. Matrigel was observed
      for transgelin (an actin stress fiber-associated protein). Transgelin was
      significantly increased in activated PSCs vs. quiescent PSCs. Silencing
      transgelin expression decreased PSC proliferation and also reduced platelet
      derived growth factor-induced PSC migration. Notably, transgelin was highly
      expressed in chronic pancreatitis in stromal areas and periacinar spaces but was
      absent in acinar cells. These findings suggest that transgelin is a potentially
      useful target protein to modulate PSC function so as to ameliorate pancreatic
      fibrosis.

PMID- 23868412
TI  - Regional susceptibility to stress-induced intestinal injury in the mouse.
AB  - Injury to the intestinal mucosa is a life-threatening problem in a variety of
      clinical disorders, including hemorrhagic shock, trauma, burn, pancreatitis, and
      heat stroke. The susceptibility to injury of different regions of intestine in
      these disorders is not well understood. We compared histological injury across
      the small intestine in two in vivo mouse models of injury, hemorrhagic shock (30%
      loss of blood volume) and heat stroke (peak core temperature 42.4 degrees C). In
      both injury models, areas near the duodenum showed significantly greater mucosal
      injury and reductions in villus height. To determine if these effects were
      dependent on circulating factors, experiments were performed on isolated
      intestinal segments to test for permeability to 4-kDa FITC-dextran. The segments
      were exposed to hyperthermia (42 degrees C for 90 min), moderate simulated
      ischemia (Po2 ~30 Torr, Pco2 ~60 Torr, pH 7.1), severe ischemia (Po2 ~20 Torr,
      Pco2 ~80 Torr, pH 6.9), or severe hypoxia (Po2 ~0 Torr, Pco2 ~35 Torr) for 90
      min, and each group was compared with sham controls. All treatments resulted in
      marked elevations in permeability within segments near the duodenum. In severe
      hypoxia or hyperthermia, permeability was also moderately elevated in the jejunum
      and ileum; in moderate or severe ischemia, permeability was unaffected in these
      regions. The results demonstrate increased susceptibility of proximal regions of
      the small intestine to acute stress-induced damage, irrespective of circulating
      factors. The predominant injury in the duodenum may impact the pattern of acute
      inflammatory responses arising from breach of the intestinal barrier, and such
      knowledge may be useful for designing therapeutic strategies.

PMID- 23868413
TI  - Throwing some light on executive function in Parkinson's disease.

PMID- 23868414
TI  - Phenolics profile of a naturally debittering olive in comparison to regular olive
      varieties.
AB  - BACKGROUND: Hurma, an olive variety that grows in a specific area in Turkey,
      loses its bitterness before harvesting, and therefore does not need further
      processing steps for the production of table olives. The total phenol content and
      phenolic profiles of (1) this naturally debittered olive type, Hurma; (2) the
      same olive variety, but not a naturally debittered type, Erkence; and (3) another
      variety, Gemlik, which is commonly consumed as table olive, were determined
      during their maturation period for two harvest years. RESULTS: The total phenol
      content of Hurma is the lowest compared to the other types regardless of harvest
      year, which has a significant effect on the phenolic content and composition of
      individual components for all olive types. All three olive types can be
      differentiated from each other especially during the late phase of maturation
      using the phenolics profile in combination with principal component analysis.
      CONCLUSION: The natural debittering phenomenon of Hurma olive on the tree
      involves a decrease in phenol content and a change in phenol composition. The
      differentiation in phenol composition especially becomes very significant in the
      late of period of maturation.

PMID- 23868415
TI  - Vegetation feedbacks of nutrient addition lead to a weaker carbon sink in an
      ombrotrophic bog.
AB  - To study vegetation feedbacks of nutrient addition on carbon sequestration
      capacity, we investigated vegetation and ecosystem CO2 exchange at Mer Bleue Bog,
      Canada in plots that had been fertilized with nitrogen (N) or with N plus
      phosphorus (P) and potassium (K) for 7-12 years. Gross photosynthesis, ecosystem
      respiration, and net CO2 exchange were measured weekly during May-September 2011
      using climate-controlled chambers. A substrate-induced respiration technique was
      used to determine the functional ability of the microbial community. The highest
      N and NPK additions were associated with 40% less net CO2 uptake than the
      control. In the NPK additions, a diminished C sink potential was due to a 20-30%
      increase in ecosystem respiration, while gross photosynthesis rates did not
      change as greater vascular plant biomass compensated for the decrease in Sphagnum
      mosses. In the highest N-only treatment, small reductions in gross photosynthesis
      and no change in ecosystem respiration led to the reduced C sink. Substrate
      induced microbial respiration was significantly higher in all levels of NPK
      additions compared with control. The temperature sensitivity of respiration in
      the plots was lower with increasing cumulative N load, suggesting more labile
      sources of respired CO2 . The weaker C sink potential could be explained by
      changes in nutrient availability, higher woody : foliar ratio, moss loss, and
      enhanced decomposition. Stronger responses to NPK fertilization than to N-only
      fertilization for both shrub biomass production and decomposition suggest that
      the bog ecosystem is N-P/K colimited rather than N-limited. Negative effects of
      further N-only deposition were indicated by delayed spring CO2 uptake. In
      contrast to forests, increased wood formation and surface litter accumulation in
      bogs seem to reduce the C sink potential owing to the loss of peat-forming
      Sphagnum.

PMID- 23868416
TI  - Hybrid carbon source for producing nitrogen-doped polymer nanodots: one-pot
      hydrothermal synthesis, fluorescence enhancement and highly selective detection
      of Fe(III).
AB  - Polymer nanodots (PNDs) from a hybrid carbon source (glucose and glycine) which
      exhibit a stronger fluorescence than the PNDs from a single source (glucose or
      glycine) are obtained by one-pot hydrothermal treatment. It is attractive that
      PNDs can be used as an effective fluorescent probe for the detection of iron ions
      with good selectivity and sensitivity in an aqueous solution. 

PMID- 23868417
TI  - Liposomal nanotransporter for targeted binding based on nucleic acid anchor
      system.
AB  - Microfluidic techniques have been developed intensively in recent years due to
      lower reagent consumption, faster analysis, and possibility of the integration of
      several analytical detectors into one chip. Electrochemical detectors are
      preferred in microfluidic systems, whereas liposomes can be used for
      amplification of the electrochemical signals. The aim of this study was to design
      a nanodevice for targeted anchoring of liposome as transport device. In this
      study, liposome with encapsulated Zn(II) was prepared. Further, gold
      nanoparticles were anchored onto the liposome surface allowing binding of thiol
      moiety-modified molecules (DNA). For targeted capturing of the transport device,
      DNA loops were used. DNA loops were represented by paramagnetic microparticles
      with oligo(DT)25 chain, on which a connecting DNA was bound. Capturing of
      transport device was subsequently done by hybridization to the loop. The
      individual steps were analyzed by electrochemistry and UV/Vis spectrometry. For
      detection of Zn(II) encapsulated in liposome, a microfluidic system was used. The
      study succeeded in demonstrating that liposome is suitable for the transport of
      Zn(II) and nucleic acids. Such transporter may be used for targeted binding using
      DNA anchor system. 

PMID- 23868418
TI  - Naringenin enhances intestinal barrier function through the expression and
      cytoskeletal association of tight junction proteins in Caco-2 cells.
AB  - SCOPE: We have previously reported that naringenin promotes the tight junction
      (TJ) integrity in intestinal Caco-2 cells. This study investigated the naringenin
      mediated effect in Caco-2 cells with a particular focus on the modulation of TJ
      structure and claudin-4 transcriptional regulation. METHODS AND RESULTS:
      Naringenin (10~100 MUM) dose-dependently enhanced TJ barrier integrity of Caco-2
      cells, indicated by transepithelial electrical resistance and FITC-dextran flux.
      Immunoblot analysis showed that naringenin increased the cytoskeletal association
      of TJ proteins, zonula occludens-2, occludin, claudin-1, and claudin-4,
      simultaneously with increased occludin phosphorylation. The total expression of
      claudin-4 was also increased by naringenin. Quantitative RT-PCR and luciferase
      reporter assay revealed that naringenin transcriptionally increased the claudin-4
      expression with activation of claudin-4 promoter. The mutation of the binding
      site of the transcriptional factor Sp1 in the claudin-4 promoter sequence and the
      pharmacological inhibition of Sp1 partially suppressed the naringenin-mediated
      activation of the claudin-4 promoter. Further, naringenin induced the heat shock
      protein 70 expression in the cells. CONCLUSION: Naringenin enhances barrier
      integrity through the assembly and expression of TJ proteins in intestinal
      epithelial cells. Naringenin-mediated claudin-4 expression occurs, at least
      partially, through Sp1-dependent transcriptional regulation. The induction of
      heat shock protein 70 may be also involved in the increased claudin-4 expression.

PMID- 23868420
TI  - JC virus granule cell neuronopathy and GCN-IRIS under natalizumab treatment.
AB  - Progressive multifocal leukoencephalopathy is the most common clinical
      presentation of JC virus (JCV)-associated central nervous system (CNS) disease
      and has emerged as a major safety concern in multiple sclerosis patients treated
      with the monoclonal antibody natalizumab. Here we report clinical, radiological,
      and histological findings of a case of cerebellar granule cell neuronopathy
      (GCN), a JCV-associated CNS disease, so far unreported amongst patients treated
      with natalizumab. GCN should be considered as a JCV CNS manifestation in patients
      with newly developed, progressive cerebellar signs under natalizumab treatment,
      especially in cases where cerebellar atrophy can be visualized by magnetic
      resonance imaging.

PMID- 23868419
TI  - Psychosocial functioning and depressive symptoms among HIV-positive persons
      receiving care and treatment in Kenya, Namibia, and Tanzania.
AB  - In sub-Saharan Africa, the prevalence of depressive symptoms among people living
      with HIV (PLHIV) is considerably greater than that among members of the general
      population. It is particularly important to treat depressive symptoms among PLHIV
      because they have been associated with poorer HIV care-related outcomes. This
      study describes overall psychosocial functioning and factors associated with
      depressive symptoms among PLHIV attending HIV care and treatment clinics in
      Kenya, Namibia, and Tanzania. Eighteen HIV care and treatment clinics (six per
      country) enrolled approximately 200 HIV-positive patients (for a total of 3,538
      participants) and collected data on patients' physical and mental well-being,
      medical/health status, and psychosocial functioning. Although the majority of
      participants did not report clinically significant depressive symptoms (72 %), 28
      % reported mild to severe depressive symptoms, with 12 % reporting severe
      depressive symptoms. Regression models indicated that greater levels of
      depressive symptoms were associated with: (1) being female, (2) younger age, (3)
      not being completely adherent to HIV medications, (4) likely dependence on
      alcohol, (5) disclosure to three or more people (versus one person), (6)
      experiences of recent violence, (7) less social support, and (8) poorer physical
      functioning. Participants from Kenya and Namibia reported greater depressive
      symptoms than those from Tanzania. Approximately 28 % of PLHIV reported
      clinically significant depressive symptoms. The scale-up of care and treatment
      services in sub-Saharan Africa provides an opportunity to address psychosocial
      and mental health needs for PLHIV as part of comprehensive care. 

PMID- 23868421
TI  - Robotic general surgery experience: a gradual progress from simple to more
      complex procedures.
AB  - BACKGROUND: Robotic surgery was introduced at our institution in 2003, and we
      used a progressive approach advancing from simple to more complex procedures.
      METHODS: A retrospective chart review. RESULTS: Cases included totalled 129. Set
      up and operative times have improved over time and with experience. Conversion
      rates to standard laparoscopic or open techniques were 4.7% and 1.6%,
      respectively. Intraoperative complications (6.2%), blood loss and hospital stay
      were directly proportional to complexity. There were no mortalities and the
      postoperative complication rate (13.2%) was within accepted norms. CONCLUSION:
      Our findings suggest that robot technology is presently most useful in cases
      tailored toward its advantages, i.e. those confined to a single space, those that
      require performance of complex tasks, and re-do procedures.

PMID- 23868422
TI  - Vitamin D insufficiency in patients with THA: prevalence and effects on outcome.
AB  - BACKGROUND: The consequences of vitamin D insufficiency in the elderly remain
      controversial. The prevalence and potential effects of its chronic insufficiency
      on quality of life and physical function in patients undergoing THA have received
      little attention. QUESTION/PURPOSES: We determined (1) prevalence of preoperative
      vitamin D insufficiency in patients undergoing THA and (2) relationships of
      insufficiency to patient-perceived outcomes (PPOs) and hip scores. METHODS: We
      retrospectively reviewed 62 consecutive patients who underwent 66 primary THAs.
      We excluded two patients with missing data and the second hip of bilateral THAs,
      leaving 60 patients (60 hips) for final inclusion. Based on preoperative plasma
      25-hydroxyvitamin-D3 levels, patients were retrospectively assigned into a normal
      or insufficient group. We used two different thresholds (20 and 30 ng/mL) to
      define insufficiency; groups were set twice. We compared demographics, BMI,
      American Society of Anesthesiologists score, Charlson Comorbidity Index; albumin,
      transferrin, calcium levels; and total lymphocyte count between groups. The
      insufficient group had a higher mean BMI with the 20-ng/mL cutoff but not with
      the 30-ng/mL cutoff. We compared the 20-ng/mL cutoff groups (adjusting for BMI)
      and the 30-ng/mL cutoff groups in terms of preoperative and postoperative Quality
      of Well-being Scale, SF-36, WOMAC, Harris hip, and Merle d'Aubigne-Postel scores.
      Mean followup was 11 months (range, 3-24 months). RESULTS: The prevalence of
      vitamin D insufficiency was 30% (using 20 ng/mL) and 65% (using 30 ng/mL).
      Preoperative and postoperative Harris hip and Merle d'Aubigne-Postel scores were
      lower in patients with insufficiency using 30 ng/mL. No differences in PPOs or
      hip scores were found using 20 ng/mL. CONCLUSIONS: Hypovitaminosis D was common
      in patients with THA and associated with lower hip scores. Standardization of the
      definition of hypovitaminosis D is urgently needed so that further studies can
      properly evaluate its real prevalence, potential negative effects on function,
      and therapeutic effects of reversing insufficiency before THA.

PMID- 23868424
TI  - CORR Insights(r): outcome of one-stage cementless exchange for acute
      postoperative periprosthetic hip infection.

PMID- 23868423
TI  - The phosphaturic mesenchymal tumor: why is definitive diagnosis and curative
      surgery often delayed?
AB  - BACKGROUND: Tumor-induced osteomalacia is a paraneoplastic syndrome resulting in
      renal phosphate wasting and decreased bone mineralization. Phosphaturic
      mesenchymal tumors represent a rare etiology of tumor-induced osteomalacia.
      Nonspecific symptoms of fatigue, bone pain, and musculoskeletal weakness make the
      diagnosis elusive and lead to a delay in surgical treatment. QUESTIONS/PURPOSES:
      In this case series, the following three questions were asked: (1) How do the
      clinical presentation and features of phosphaturic mesenchymal tumors delay the
      diagnosis? (2) What is the clinical course after surgical treatment of
      phosphaturic mesenchymal tumors? (3) How frequently do phosphaturic mesenchymal
      tumors recur and are there factors associated with recurrence? METHODS: This
      study retrospectively reviewed the cases of five adults diagnosed and treated for
      phosphaturic mesenchymal tumors. Patients were identified through an internal
      orthopaedic oncology database with clinical, surgical, and histologic data
      obtained through a systematic chart review. RESULTS: Five patients presented with
      a long-standing history of osteomalacia, generalized fatigue, pain, and weakness
      before the diagnosis was reached at an average of 7.2 years (range, 2-12 years)
      after initial symptom onset. The diagnosis appeared to be delayed owing to the
      cryptic medical presentation, difficulty in locating tumor by imaging, and
      confirming histologic appearance. Two patients treated with wide surgical
      resection did not experience recurrence compared with three patients who did show
      recurrent signs and symptoms after marginal excision. A postoperative increase in
      fibroblast-derived growth factor-23 was associated with recurrent disease.
      CONCLUSIONS: Although uncommon, the diagnosis of phosphaturic mesenchymal tumor
      should be considered in any patient who presents with hypophosphaturic
      osteomalacia and no other physiologic cause. Definitive treatment is early, wide
      surgical resection.

PMID- 23868425
TI  - The John Charnley Award: Diagnostic accuracy of MRI versus ultrasound for
      detecting pseudotumors in asymptomatic metal-on-metal THA.
AB  - BACKGROUND: The prevalence of pseudotumors in patients with large-head metal-on
      metal (MOM) THA has been the subject of implant recalls and warnings from various
      regulatory agencies. To date, there is no consensus on whether ultrasound or MRI
      is superior for the detection of pseudotumors. QUESTIONS/PURPOSES: We
      prospectively compared ultrasound to MRI for pseudotumor detection in an
      asymptomatic cohort of patients with MOM THAs. We also compared ultrasound to MRI
      for assessment of pseudotumor growth and progressive soft tissue involvement at a
      6-month interval. METHODS: We enrolled 40 patients with large-head MOM THAs in
      the study. The mean age was 54 years (range, 34-76 years). The mean time from
      surgery was 54 months (range, 40-81 months). There were 28 men and 12 women. All
      patients underwent ultrasound and MRI using slice encoding for metal artifact
      correction. The gold standard was defined as follows: if both ultrasound and MRI
      agreed, this was interpreted as concordant and the result was considered
      accurate. RESULTS: Ultrasound and MRI agreed in 37 of 40 patients (93%). The
      prevalence of pseudotumors was 31% (12 of 39) in our cohort. Twenty-three of 39
      patients (59%) had completely normal tests and four (10%) had simple fluid
      collections. Ultrasound had a sensitivity of 100% and specificity of 96% while
      MRI had a sensitivity of 92% and specificity of 100%. CONCLUSIONS: A negative
      ultrasound rules out pseudotumor in asymptomatic patients as this test is 100%
      sensitive. Given its lower cost, we recommend ultrasound as the initial screening
      tool for pseudotumors.

PMID- 23868428
TI  - Comparison of voice and swallowing parameters after endoscopic total and partial
      arytenoidectomy for bilateral abductor vocal fold paralysis: a randomized trial.
AB  - IMPORTANCE: Total arytenoidectomy is claimed to increase risk of aspiration and
      cause more voice loss than other operations performed for bilateral abductor
      vocal fold paralysis (BVFP). However, objective evidence for such a conclusion is
      lacking. There is no study comparing swallowing and voice after total and partial
      arytenoidectomy. OBJECTIVE: To compare voice and swallowing parameters after
      endoscopic total and partial arytenoidectomy for BVFP. DESIGN, SETTING, AND
      PARTICIPANTS: In this prospective, randomized, double-blind, case-control study
      conducted at a tertiary referral university, the study population comprised 20
      patients with BVFP. INTERVENTIONS: Endoscopic total and partial arytenoidectomy.
      MAIN OUTCOMES AND MEASURES: Decannulation, duration of operation, Voice Handicap
      Index, acoustic and aerodynamic analysis, postoperative breathing ability,
      subjective comparison of preoperative and postoperative voice, speech intensity,
      and functional outcome swallowing scale. RESULTS: Median duration of partial and
      total arytenoidectomies were 59 and 49 minutes, respectively. This difference was
      statistically significant (P = .04). Comparisons of preoperative and
      postoperative Voice Handicap Index, acoustic and aerodynamic measures,
      postoperative breathing ability, subjective comparison of preoperative and
      postoperative voice, speech intensity, and functional outcome swallowing scale
      were not statistically significantly different between both groups. CONCLUSIONS
      AND RELEVANCE: Endoscopic total and partial arytenoidectomy are very successful
      static surgical options for BVFP. Partial takes longer than total
      arytenoidectomy. They both provide a comfortable airway, acceptable voice, and
      acceptable deglutition. It may be a sound practice to perform partial
      arytenoidectomy initially for primary BVFP cases and reserve total
      arytenoidectomy for revision cases. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01824849.

PMID- 23868427
TI  - Adjuvant intraoperative photodynamic therapy in head and neck cancer.
AB  - IMPORTANCE: There is an immediate need to develop local intraoperative adjuvant
      treatment strategies to improve outcomes in patients with cancer who undergo head
      and neck surgery. OBJECTIVES: To determine the safety of photodynamic therapy
      with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with
      surgery in patients with head and neck squamous cell carcinoma. DESIGN, SETTING,
      AND PARTICIPANTS: Nonrandomized, single-arm, single-site, phase 1 study at a
      comprehensive cancer center among 16 adult patients (median age, 65 years) with
      biopsy-proved primary or recurrent resectable head and neck squamous cell
      carcinoma. INTERVENTIONS: Intravenous injection of HPPH (4.0 mg/m2), followed by
      activation with 665-nm laser light in the surgical bed immediately after tumor
      resection. MAIN OUTCOMES AND MEASURES: Adverse events and highest laser light
      dose. RESULTS: Fifteen patients received the full course of treatment, and 1
      patient received HPPH without intraoperative laser light because of an unrelated
      myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6
      patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient,
      who received HPPH only). The most frequent adverse events related to photodynamic
      therapy were mild to moderate edema (9 patients) and pain (3 patients). One
      patient developed a grade 3 fistula after salvage laryngectomy, and another
      patient developed a grade 3 wound infection and mandibular fracture.
      Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate
      skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter).
      The highest laser light dose was 75 J/cm2. CONCLUSIONS AND RELEVANCE: The
      adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous
      cell carcinoma seems safe and deserves further study. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00470496.

PMID- 23868429
TI  - Sensitivity and specificity of eustachian tube function tests in adults.
AB  - IMPORTANCE: The study demonstrates the utility of eustachian tube (ET) function
      (ETF) test results for accurately assigning ears to disease state. OBJECTIVES: To
      determine if ETF tests can identify ears with physician-diagnosed ET dysfunction
      (ETD) in a mixed population at high sensitivity and specificity and to define the
      interrelatedness of ETF test parameters. DESIGN, SETTING, AND PARTICIPANTS:
      Through use of the forced-response, inflation-deflation, Valsalva, and sniffing
      tests, ETF was evaluated in 15 control ears of adult subjects after unilateral
      myringotomy (group 1) and in 23 ears of 19 adult subjects with ventilation tubes
      inserted for ETD (group 2). Data were analyzed using logistic regression
      including each parameter independently and then a step-down discriminant analysis
      including all ETF test parameters to predict group assignment. Factor analysis
      operating over all parameters was used to explore relatedness. EXPOSURES: ETF
      testing. MAIN OUTCOMES AND MEASURES: ETF parameters for the forced response,
      inflation-deflation, Valsalva, and sniffing tests measured in 15 control ears of
      adult subjects after unilateral myringotomy (group 1) and in 23 ears of 19 adult
      subjects with ventilation tubes inserted for ETD (group 2). RESULTS: The
      discriminant analysis identified 4 ETF test parameters (Valsalva, ET opening
      pressure, dilatory efficiency, and percentage of positive pressure equilibrated)
      that together correctly assigned ears to group 2 at a sensitivity of 95% and a
      specificity of 83%. Individual parameters representing the efficiency of ET
      opening during swallowing showed moderately accurate assignments of ears to their
      respective groups. Three factors captured approximately 98% of the variance among
      parameters: the first had negative loadings of the ETF structural parameters; the
      second had positive loadings of the muscle-assisted ET opening parameters; and
      the third had negative loadings of the muscle-assisted ET opening parameters and
      positive loadings of the structural parameters. CONCLUSIONS AND RELEVANCE: These
      results show that ETF tests can correctly assign individual ears to physician
      diagnosed ETD with high sensitivity and specificity and that ETF test parameters
      can be grouped into structural-functional categories.

PMID- 23868430
TI  - Interleukin 6 in hyposmia.
AB  - IMPORTANCE: Olfaction is a complex sensory process that has not been fully
      studied. Elevated plasma levels of interleukin 6 (IL-6) have been found in
      patients with several acute and chronic diseases but have not been reported in
      patients with smell loss (hyposmia). OBJECTIVE: To determine IL-6 levels in
      patients with hyposmia. DESIGN: Retrospective study. All measurements were made
      without reference to the origin of any collected sample. SETTING An ambulatory
      private practice at The Taste and Smell Clinic in Washington, DC. PARTICIPANTS:
      Fifty-nine consecutive patients who presented to the clinic between 2005 and 2008
      for evaluation and treatment of various degrees of hyposmia were studied. Nine
      volunteers with normal sensory function served as controls. MAIN OUTCOMES AND
      MEASURES: Levels of IL-6 were measured in samples of plasma, urine, saliva, and
      nasal mucus. RESULTS: All biological fluid samples studied contained IL-6. Mean
      (SEM) levels in plasma, saliva, and nasal mucus in patients were significantly
      higher than in controls (0.95 [0.10] vs 0.12 [0.03] pg/mL, 0.57 [0.05] vs 0.30
      [0.01] pg/mL, and 29.7 [3.8] vs 11.6 [0.5] pg/mL, respectively; all P < .001).
      The concentration of IL-6 in nasal mucus in patients was significantly higher
      than in controls and was more than 30 times higher than in any other biological
      fluid. Mean (SEM) levels in urine were not significantly different: 0.92 (0.17)
      pg/mL for patients and 1.26 (0.41) pg/mL for controls (P > .50). CONCLUSIONS AND
      RELEVANCE: Compared with controls, IL-6 in patients was significantly elevated in
      plasma, saliva, and nasal mucus. Because IL-6 is a proinflammatory cytokine,
      these changes can relate to local or systemic inflammatory processes, which can
      be a cause or a result of pathological processes associated with hyposmia. These
      results support the concept that hyposmia has a biochemical basis and IL-6 may
      play a role in biochemical pathological processes underlying hyposmia and its
      treatment.

PMID- 23868431
TI  - Laryngeal fractures in lacrosse due to high speed ball impact.
AB  - IMPORTANCE: Men's lacrosse is a fast-paced, high-collision sport with ball speeds
      in excess of 90 mph. Laryngeal fractures in lacrosse are a rarely reported
      injury. To increase awareness of this potential injury, we describe 3 male
      lacrosse players who sustained laryngeal fractures from lacrosse ball trauma to
      the neck. OBSERVATIONS: The first patient sustained a minimally displaced,
      paramedian thyroid cartilage fracture and was managed with observation alone. The
      second patient sustained a depressed fracture of the left thyroid ala and was
      managed with closed reduction. The third case sustained a mildly displaced
      transcricoid fracture. He was managed with open reduction and internal fixation.
      All 3 patients returned to regular activities with near normal voice results by
      final follow-up. CONCLUSIONS AND RELEVANCE: This is the first report of laryngeal
      fractures following lacrosse ball trauma to the neck. Lacrosse players are at
      risk for laryngeal injuries, and neck protection is only worn by the goalie. It
      is our hope that this series will raise awareness of this potentially lethal
      injury and prompt the sport to consider mandatory neck protection for all
      players.

PMID- 23868432
TI  - Subglottic presentation of a rare tumor: primary or metastatic? Primary mucosal
      melanoma of the subglottic larynx.

PMID- 23868433
TI  - Tumor of maxilla in a patient with hypercalcemia. Brown tumor of primary
      hyperparathyroidism.

PMID- 23868434
TI  - Intermittent hemoptysis and blood-tinged sputum. Castleman disease (CD), hyaline
      vascular type.

PMID- 23868435
TI  - A nasal mass. Nasal dermoid ND cyst.

PMID- 23868436
TI  - Chronic right-sided otorrhea. Langerhans cell histiocytosis (LCH).

PMID- 23868438
TI  - Hepatocellular carcinoma screening practices in the Department of Veterans
      Affairs: findings from a national facility survey.
AB  - BACKGROUND: Previous studies suggest low rates of hepatocellular carcinoma (HCC)
      screening in clinical practice. There is little information on the provider- and
      healthcare-facility-related factors that explain the use of HCC screening. AIMS:
      We used data from the 2007 Survey to Assess Hepatitis C Care in Veterans Health
      Administration that collected information regarding the care of patients with
      hepatitis C virus (HCV) from 138 of 140 Veterans Administration healthcare
      facilities nationwide. METHODS: All providers caring for veterans with HCV were
      invited to respond. In addition, each facility was asked to identify a lead HCV
      clinician to respond to facility-specific questions. Our outcome was a response
      concordant with HCC screening guidelines [HCC screening in patients with
      cirrhosis or in patients with chronic hepatitis B virus (HBV), and screening
      every 6 or 12 months]. RESULTS: A total of 268 providers responded (98 % facility
      participation rate). Of these, 190 respondents (70.9 %) reported recommending HCC
      screening with guideline-concordant risk groups and frequency. Providers
      reporting guideline-concordant HCC screening practices were significantly more
      likely to have expertise in liver disease (MD, gastroenterologists or
      hepatologists), routinely screen for varices, prescribe HCV treatment, and refer
      or manage patients with liver transplant. The availability of HCC-specific
      treatments on site was the main facility factor associated with guideline
      concordant HCC screening. CONCLUSIONS: Self-reported rates of guideline
      concordant HCC screening are considerably higher than those seen in routine VA
      practice. Provider expertise in liver disease and the perceived availability of
      HCC treatment including transplantation in the local facility are important
      factors driving self-reported HCC screening practices.

PMID- 23868440
TI  - Biodiversity conservation in a changing climate: a review of threats and
      implications for conservation planning in Myanmar.
AB  - High levels of species richness and endemism make Myanmar a regional priority for
      conservation. However, decades of economic and political sanctions have resulted
      in low conservation investment to effectively tackle threats to biodiversity.
      Recent sweeping political reforms have placed Myanmar on the fast track to
      economic development-the expectation is increased economic investments focused on
      the exploitation of the country's rich, and relatively intact, natural resources.
      Within a context of weak regulatory capacity and inadequate environmental
      safeguards, rapid economic development is likely to have far-reaching negative
      implications for already threatened biodiversity and natural-resource-dependent
      human communities. Climate change will further exacerbate prevailing threats
      given Myanmar's high exposure and vulnerability. The aim of this review is to
      examine the implications of increased economic growth and a changing climate
      within the larger context of biodiversity conservation in Myanmar. We summarize
      conservation challenges, assess direct climatological impacts on biodiversity and
      conclude with recommendations for long-term adaptation approaches for
      biodiversity conservation. 

PMID- 23868441
TI  - Reactivity of Dialumane and "Dialumene" Compounds toward Alkenes.
AB  - The reactions of dialumane [L(thf)Al-Al(thf)L] (1, L=[{(2,6-iPr2C6H3)NC(Me)}2](2
      )) with stilbene and styrene afforded the oxidation/insertion products
      [L(thf)Al(CH(Ph)-CH(Ph))AlL] (2) and [L(thf)Al(CH(Ph)-CH2)Al(thf)L] (3),
      respectively. In the presence of Na metal, precursor 1 reacted with butadienes,
      possibly through the reduced "dialumene" or the "carbene-like" :AlL species, to
      yield aluminacyclopentenes [LAl(CH2C(Me)=C(Me)CH2)Na]n (4 a) and
      [Na(dme)3][LAl(CH2C(Me)=CHCH2)] (4 b, dme=dimethoxyethane) as [1+4] cycloaddition
      products, as well as the [2+4] cycloaddition product 1,6-dialumina-3,8
      cyclodecadiene, [{Na(dme)}2][LAl(CH2C(Me)=C(Me)CH2)2AlL] (5). The possible
      mechanisms of the cycloaddition reactions were studied by using DFT computations.

PMID- 23868442
TI  - Magnetic resonance-guided focused ultrasound myomectomy: safety, efficacy,
      subsequent fertility and quality-of-life improvements, a systematic review.
AB  - We performed a systematic review about studies reporting data of myomectomy
      performed by magnetic resonance-guided focused ultrasound (MRgFUS) technique in
      order to define its safety, feasibility, indications, complications, and impact
      on uterine fibroid symptom and health-related quality of life (UFS-QOL) and
      fertility. Outcomes were considered according to fibroids shrinkage, nonperfused
      volume (NPV), NPV ratio, and uterine fibroid symptoms assessed with UFS-QOL
      questionnaire (baseline 3, 4, 6, and 12 months). We analyzed 38 eligible studies
      reporting outcomes about 2500 patients (mean age 43.67 years). The MRgFUS results
      a safe, efficient, and cost-effective minimal invasive technique for treatment of
      uterine fibroids. Increasing experience, device improvements, and availability
      for a larger number of patients are enhancing the outcomes, while the obstetrical
      ones should be more extensively explored. The MRgFUS could be considered as a
      minimal invasive alternative to traditional surgical or radiological procedures
      for the treatment of symptomatic uterine myomas improving both QOL and subsequent
      fertility. 

PMID- 23868443
TI  - The water R1(omega) NMRD profiles of a hydrated protein from molecular dynamics
      simulation.
AB  - The hydration of a protein, Peroxiredoxin 5, is obtained from a molecular
      dynamics simulation and compared with the picture of hydration which is obtained
      by analysing the water proton R1 NMRD profiles using a generally accepted
      relaxation model [K. Venu, V. P. Denisov and B. Halle, J. Am. Chem. Soc., 1997,
      119, 3122]. The discrepancy between the hydration pictures derived from the water
      R1(omega0)-NMRD profiles and MD is relevant in a discussion of the factors behind
      the stretched NMRD profile, the distribution of orientational order parameters
      and residence times of buried water used in the NMRD model. 

PMID- 23868444
TI  - A multi-scale spatial analysis of native and exotic plant species richness within
      a mixed-disturbance oak savanna landscape.
AB  - Impacts of human land use pose an increasing threat to global biodiversity.
      Resource managers must respond rapidly to this threat by assessing existing
      natural areas and prioritizing conservation actions across multiple spatial
      scales. Plant species richness is a useful measure of biodiversity but typically
      can only be evaluated on small portions of a given landscape. Modeling
      relationships between spatial heterogeneity and species richness may allow
      conservation planners to make predictions of species richness patterns within
      unsampled areas. We utilized a combination of field data, remotely sensed data,
      and landscape pattern metrics to develop models of native and exotic plant
      species richness at two spatial extents (60- and 120-m windows) and at four
      ecological levels for northwestern Ohio's Oak Openings region. Multiple
      regression models explained 37-77 % of the variation in plant species richness.
      These models consistently explained more variation in exotic richness than in
      native richness. Exotic richness was better explained at the 120-m extent while
      native richness was better explained at the 60-m extent. Land cover composition
      of the surrounding landscape was an important component of all models. We found
      that percentage of human-modified land cover (negatively correlated with native
      richness and positively correlated with exotic richness) was a particularly
      useful predictor of plant species richness and that human-caused disturbances
      exert a strong influence on species richness patterns within a mixed-disturbance
      oak savanna landscape. Our results emphasize the importance of using a multi
      scale approach to examine the complex relationships between spatial heterogeneity
      and plant species richness. 

PMID- 23868445
TI  - Participatory evaluation of monitoring and modeling of sustainable land
      management technologies in areas prone to land degradation.
AB  - Examples of sustainable land management (SLM) exist throughout the world. In many
      cases, SLM has largely evolved through local traditional practices and
      incremental experimentation rather than being adopted on the basis of scientific
      evidence. This means that SLM technologies are often only adopted across small
      areas. The DESIRE (DESertIfication mitigation and REmediation of degraded land)
      project combined local traditional knowledge on SLM with empirical evaluation of
      SLM technologies. The purpose of this was to evaluate and select options for
      dissemination in 16 sites across 12 countries. It involved (i) an initial
      workshop to evaluate stakeholder priorities (reported elsewhere), (ii) field
      trials/empirical modeling, and then, (iii) further stakeholder evaluation
      workshops. This paper focuses on workshops in which stakeholders evaluated the
      performance of SLM technologies based on the scientific monitoring and modeling
      results from 15 study sites. It analyses workshop outcomes to evaluate how
      scientific results affected stakeholders' perceptions of local SLM technologies.
      It also assessed the potential of this participatory approach in facilitating
      wider acceptance and implementation of SLM. In several sites, stakeholder
      preferences for SLM technologies changed as a consequence of empirical
      measurements and modeling assessments of each technology. Two workshop examples
      are presented in depth to: (a) explore the scientific results that triggered
      stakeholders to change their views; and (b) discuss stakeholders' suggestions on
      how the adoption of SLM technologies could be up-scaled. The overall multi
      stakeholder participatory approach taken is then evaluated. It is concluded that
      to facilitate broad-scale adoption of SLM technologies, de-contextualized,
      scientific generalisations must be given local context; scientific findings must
      be viewed alongside traditional beliefs and both scrutinized with equal rigor;
      and the knowledge of all kinds of experts must be recognised and considered in
      decision-making about SLM, whether it has been formally codified or not. The
      approach presented in this paper provided this opportunity and received positive
      feedback from stakeholders.

PMID- 23868446
TI  - Bio-responsive polymer hydrogels homeostatically regulate blood coagulation.
AB  - Bio-responsive polymer architectures can empower medical therapies by engaging
      molecular feedback-response mechanisms resembling the homeostatic adaptation of
      living tissues to varying environmental constraints. Here we show that a blood
      coagulation-responsive hydrogel system can deliver heparin in amounts triggered
      by the environmental levels of thrombin, the key enzyme of the coagulation
      cascade, which--in turn--becomes inactivated due to released heparin. The bio
      responsive hydrogel quantitatively quenches blood coagulation over several hours
      in the presence of pro-coagulant stimuli and during repeated incubation with
      fresh, non-anticoagulated blood. These features enable the introduced material to
      provide sustainable, autoregulated anticoagulation, addressing a key challenge of
      many medical therapies. Beyond that, the explored concept may facilitate the
      development of materials that allow the effective and controlled application of
      drugs and biomolecules.

PMID- 23868447
TI  - Application of an improved magnetic immunosorbent in an Ephesia chip designed for
      circulating tumor cell capture.
AB  - In this study, we describe a particular step in developing a microfluidic device
      for capture and detection of circulating tumor cells-specifically the preparation
      of an immunosorbent for implementation into the separation chip. We highlight
      some of the most important specifics connected with superparamegnetic
      microspheres for microfluidic purposes. Factors such as nonspecific adsorption on
      microfluidic channels, interactions with model cell lines, and tendency to
      aggregation were investigated. Poly(glycidyl methacrylate) microspheres with
      carboxyl groups were employed for this purpose. To address the aforementioned
      challenges, the microspheres were coated with hydrazide-PEG-hydrazide, and
      subsequently anti-epithelial cell adhesion molecule (EpCAM) antibody was
      immobilized. The prepared anti-EpCAM immunosorbent was pretested using model cell
      lines with differing EpCAM density (MCF7, SKBR3, A549, and Raji) in a batchwise
      arrangement. Finally, the entire system was implemented and studied in an Ephesia
      chip and an evaluation was performed by the MCF7 cell line. 

PMID- 23868448
TI  - Management and prognosis of primary tracheal cancer: a national analysis.
AB  - OBJECTIVES/HYPOTHESIS: To perform a national review of the incidence and
      treatment of primary tracheal cancer and to identify gaps in service provision
      and factors associated with survival. STUDY DESIGN: Retrospective analysis of
      Hospital Episode Statistics data for England between 1996 and 2011. METHODS:
      Information about age, sex, morbidity, provider trust, diagnostic delay, nature
      of hospital admission and treatment, and palliation-free survival were recorded.
      The relationship between variables and survival was explored with Cox regression.
      RESULTS: There were 874 patients, giving an incidence of 0.9 per million. Mean
      age at diagnosis was 66 +/- 13, and there were 456 (52%) males. Mean presentation
      to diagnosis latency was 2.5 +/- 8 months, and 40% of patients presented as
      emergency admissions. There were 19 cases of oesophageal involvement and 241
      cases of bronchopulmonary involvement; and 188 patients developed distant
      metastases. There were 60 curative resections (6.9%), which was the most
      significant predictor of palliation-free survival (hazard ratio: 0.23; 95%
      confidence interval 0.13-0.38). Other prognostic variables included age, sex,
      emergency admission, interventional bronchoscopy, chemotherapy, oesophageal
      involvement, and distant metastases. Ten-year palliation-free survival was 60.8%
      with curative resection and 19.5% overall. Eighty-six percent of patients were
      treated in units that treated fewer than one patient per year. CONCLUSION:
      Tracheal cancer is under-recognized and under-treated. Early diagnosis, access to
      interventional bronchoscopy, and surgical treatment in specialist units may
      improve the survival of patients with this condition.

PMID- 23868449
TI  - Expression of NAD(H) kinase and glucose-6-phosphate dehydrogenase improve NADPH
      supply and L-isoleucine biosynthesis in Corynebacterium glutamicum ssp.
      lactofermentum.
AB  - Corynebacterium glutamicum is the workhorse for the production of amino acids,
      including L-isoleucine (Ile). During Ile biosynthesis, NADPH is required as a
      crucial cofactor. In this study, four NADPH-supplying strategies based on NAD
      kinase, NADH kinase, glucose-6-phosphate dehydrogenase, and NAD kinase coupling
      with glucose-6-phosphate dehydrogenase were compared, and their influences on Ile
      biosynthesis were examined. PpnK is a NAD kinase of C. glutamicum ssp.
      lactofermentum JHI3-156 that predominantly phosphorylates NAD(+) to produce
      NADP(+). Pos5 is a NADH kinase of Saccharomyces cerevisiae that predominantly
      phosphorylates NADH to produce NADPH. Zwf is a glucose-6-phosphate dehydrogenase
      of JHI3-156. The ppnK, POS5, zwf, and zwf-ppnK genes were overexpressed in the
      Ile-producing strain JHI3-156. The expression of all four genes increased
      intracellular NADPH concentration and Ile production. The increase of NADPH
      concentration and Ile production in a POS5-expressing strain (229 and 75.6 %,
      respectively) was higher than that in a ppnK-expression strain. The expression of
      zwf also increased NADPH supply and Ile biosynthesis, but the constitutive
      expression of zwf was not as effective as the inducible expression of zwf.
      Coexpression of zwf and ppnK genes greatly enhanced NADPH supply and thus
      improved Ile production by up to 85.9 %, indicating that this strategy was the
      most effective one. These results are helpful for improving Ile biosynthesis and
      other biosynthetic processes. 

PMID- 23868450
TI  - Microwave absorption enhancement, magnetic coupling and ab initio electronic
      structure of monodispersed (Mn(1-x)Co(x))3O4 nanoparticles.
AB  - Monodispersed manganese oxide (Mn1-xCox)3O4 (0 <= x <= 0.5) nanoparticles, less
      than 10 nm size, are respectively synthesized via a facile thermolysis method at
      a rather low temperature, ranging from 90 to 100  degrees C, without any inertia
      gas for protection. The influences of the Co dopant content on the critical
      reaction temperature required for the nanoparticle formation, electronic band
      structures, magnetic properties, and the microwave absorption capability of (Mn1
      xCox)3O4 are comprehensively investigated by means of both experimental and
      theoretical approaches including powder X-ray diffraction (XRD), electron energy
      loss spectroscopy (EELS), super conductivity quantum interference device (SQUID)
      examination, and first-principle simulations. Co is successfully doped into the
      Mn atomic sites of the (Mn1-xCox)3O4 lattice, which is further confirmed by EELS
      data acquired from one individual nanoparticle. Therefore, continuous solid
      solutions of well-crystallized (Mn1-xCox)3O4 products are achieved without any
      impurity phase or phase separation. With increases in the Co dopant concentration
      x from 0 to 0.5, the lattice parameters change systemically, where the overall
      saturation magnetization at 30 K increases due to the more intense coupling of
      the 3d electrons between Mn and Co, as revealed by simulations. The microwave
      absorption properties of the (Mn1-xCox)3O4 nanoparticles are examined between 2
      and 18 GHz. The maximum absorption peak -11.0 dB of the x = 0 sample is enhanced
      to -11.5 dB for x = 0.2, -12.7 dB for x = 0.25, -15.6 dB for x = 0.33, and -24.0
      dB for x = 0.5 respectively, suggesting the Co doping effects. Our results might
      provide novel insights into the understanding of the influences of metallic ion
      doping on the electromagnetic properties of metallic oxide nanomaterials. 

PMID- 23868451
TI  - Iron and neurodegeneration in the multiple sclerosis brain.
AB  - OBJECTIVE: Iron may contribute to the pathogenesis and progression of multiple
      sclerosis (MS) due to its accumulation in the human brain with age. Our study
      focused on nonheme iron distribution and the expression of the iron-related
      proteins ferritin, hephaestin, and ceruloplasmin in relation to oxidative damage
      in the brain tissue of 33 MS and 30 control cases. METHODS: We performed (1)
      whole-genome microarrays including 4 MS and 3 control cases to analyze the
      expression of iron-related genes, (2) nonheme iron histochemistry, (3)
      immunohistochemistry for proteins of iron metabolism, and (4) quantitative
      analysis by digital densitometry and cell counting in regions representing
      different stages of lesion maturation. RESULTS: We found an age-related increase
      of iron in the white matter of controls as well as in patients with short disease
      duration. In chronic MS, however, there was a significant decrease of iron in the
      normal-appearing white matter (NAWM) corresponding with disease duration, when
      corrected for age. This decrease of iron in oligodendrocytes and myelin was
      associated with an upregulation of iron-exporting ferroxidases. In active MS
      lesions, iron was apparently released from dying oligodendrocytes, resulting in
      extracellular accumulation of iron and uptake into microglia and macrophages.
      Iron-containing microglia showed signs of cell degeneration. At lesion edges and
      within centers of lesions, iron accumulated in astrocytes and axons.
      INTERPRETATION: Iron decreases in the NAWM of MS patients with increasing disease
      duration. Cellular degeneration in MS lesions leads to waves of iron liberation,
      which may propagate neurodegeneration together with inflammatory oxidative burst.

PMID- 23868453
TI  - The cancer and metabolism link: researchers increasingly target metabolism in the
      search for new cancer treatments.

PMID- 23868452
TI  - Actuated conformational switching in a single crystal of a
      homodithiacalix[4]arene.

PMID- 23868454
TI  - Study: alcohol a leading preventable cause of cancer death.

PMID- 23868455
TI  - Cancer drug shortages lead to higher costs, greater risk.

PMID- 23868456
TI  - Multicenter validation study of pathologic response and tumor thickness at the
      tumor-normal liver interface as independent predictors of disease-free survival
      after preoperative chemotherapy and surgery for colorectal liver metastases.
AB  - BACKGROUND: To validate pathologic markers of response to preoperative
      chemotherapy as predictors of disease-free survival (DFS) after resection of
      colorectal liver metastases (CLM). METHODS: One hundred seventy-one patients who
      underwent resection of CLM after preoperative chemotherapy at 4 centers were
      studied. Pathologic response-defined as the proportion of tumor cells remaining
      (complete, 0%; major, <50%; minor, >=50%) and tumor thickness at the tumor-normal
      liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, >=5 mm)-was assessed by a central
      pathology reviewer and local pathologists. RESULTS: Pathologic response was
      complete in 8% of patients, major in 49% of patients, and minor in 43% of
      patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm
      in 56% of patients, and >=5 mm in 23% of patients. On multivariate analyses,
      using either pathologic response or tumor thickness at TNI, pathologic response
      (P = .002, .009), tumor thickness at TNI (P = 0.015, <.001), duration of
      preoperative chemotherapy (P = .028, .043), number of CLM (P = .038, . 037), and
      margin (P = .011, .016) were associated with DFS. In a multivariate analysis
      using both parameters, tumor thickness at TNI (P = .004, .015), duration of
      preoperative chemotherapy (P = .025), number of nodules (P = .027), and margin (P
      = .014) were associated with DFS. Tumor size by pathology examination was the
      predictor of pathologic response. Predictors of tumor thickness at the TNI were
      tumor size and chemotherapy regimen. There was near perfect agreement for
      pathologic response (kappa = .82) and substantial agreement (kappa = .76) for
      tumor thickness between the central reviewer and local pathologists. CONCLUSIONS:
      Pathologic response and tumor thickness at the TNI are valid predictors of DFS
      after preoperative chemotherapy and surgery for CLM.

PMID- 23868458
TI  - Evaluation of a patient-reported continuity of care model for older adults.
AB  - PURPOSE: Although continuity of care (CoC) is a cornerstone of many health
      policies, there is no theoretically driven model of CoC that incorporates the
      experiences of older adults. We evaluated such a model in data collected for
      another purpose. METHODS: We used data on 2,620 Medicare beneficiaries who
      completed all of the necessary components of the 2004 National Health and Health
      Services Use Questionnaire (NHHSUQ). The NHHSUQ solicited information on usual
      primary provider, place of care, and the quality and duration of the patient
      provider relationship. We used confirmatory factor analysis to evaluate the
      patient-reported CoC model and examined factorial invariance across sex,
      race/ethnicity, Medicare plan type, and perceived health status. RESULTS: Our
      thirteen-item CoC model consisted of longitudinal (care site and provider
      duration) and interpersonal (instrumental and affective) domains. Although the
      overall chi-square goodness-of-fit statistic was significant (chi(2) = 1,091.8,
      df = 57, p < .001), model fit was good based on standard indices (GFI = 0.94, NFI
      = 0.96, CFI = 0.96, RMSEA = 0.08). Cronbach's alpha for the longitudinal care
      site (two items) and provider duration (three items) scales was 0.88 and 0.75,
      respectively, while the instrumental and affective relationship scales (four
      items each) were 0.88 and 0.87, respectively. Factorial invariance between sexes
      was observed, with relatively minor variance across race/ethnicity, Medicare plan
      type, and perceived health. CONCLUSION: We evaluated a theoretically derived
      model of CoC in older adults and found that the assessment of CoC should include
      the patient experience of both the longitudinal and the interpersonal dimensions
      of CoC.

PMID- 23868457
TI  - Cognitive interviewing of the US National Cancer Institute's Patient-Reported
      Outcomes version of the Common Terminology Criteria for Adverse Events (PRO
      CTCAE).
AB  - PURPOSE: The National Cancer Institute's Patient-Reported Outcomes version of the
      Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of
      question items that enables patient reporting of adverse events (AEs) in clinical
      trials. This study contributes content validity evidence of the PRO-CTCAE by
      incorporating cancer patient input of the relevance and comprehensiveness of the
      item library. METHODS: Cognitive interviews were conducted among patients
      undergoing chemotherapy or radiation therapy at multiple sites to evaluate
      comprehension, memory retrieval, judgment, and response mapping related to AE
      terms (e.g., nausea), attribute terms (regarding frequency, severity, or
      interference), response options, and recall period. Three interview rounds were
      conducted with >=20 patients completing each item per round. Items were modified
      and retested if >=3 patients exhibited cognitive difficulties or if experienced
      by <=25% patients. RESULTS: One hundred and twenty-seven patients participated
      (35% <=high school, 28% non-white, and 59% female). Most AE terms (63/80)
      generated no cognitive difficulties. The remaining 17 were modified without
      further difficulties by Round 3. Terms were comprehended regardless of education
      level. Attribute terms and response options required no modifications. Patient
      adherence to recall period (7 days) was improved when the reference period was
      incorporated. CONCLUSIONS: This study provides evidence confirming comprehension
      of the US English language versions of items in the PRO-CTCAE library for
      measuring symptomatic AEs from the patient perspective within the context of
      cancer treatment. Several minor changes were made to the items to improve item
      clarity, comprehension, and ease of response judgment. This study helps to
      establish the content validity of PRO-CTCAE items for patient reporting of AEs
      during cancer treatment.

PMID- 23868459
TI  - Use of factor analysis models to evaluate measurement invariance property of the
      Asthma Control Questionnaire (ACQ).
AB  - PURPOSES: To demonstrate the assessment of measurement invariance property in a
      health status instrument and to increase the awareness of its importance, we
      evaluate the measurement invariance of the Asthma Control Questionnaire (ACQ)
      across age and gender subgroups. METHODS: Data are obtained from children 7-12
      years of age at entry into a randomized trial, which evaluates the effect of a
      telephone coaching program on improving asthma outcome. Multi-group confirmatory
      factor analysis is used to assess the comparability of factor loadings and
      intercepts across age and gender subgroups. Since age is a continuous variable,
      two different categorizations (7-10 vs 11-12 and 7-9 vs 10-12) are analyzed.
      RESULTS: The factor loadings and intercepts of all six items in ACQ are
      comparable across gender subgroups. Although the factor loadings are comparable
      across age 7-10 and 11-12 subgroups, one intercept is statistically but not
      practically different. For age 7-9 versus 10-12 subgroup comparison, the factor
      loadings are not comparable. CONCLUSION: In children, the ACQ can be used to
      compare asthma control construct between boys and girls and between age 7-10 and
      11-12 subgroups. Measurement invariance is an important property that should be
      examined when the latent construct(s) are compared across different subgroups.

PMID- 23868460
TI  - Pathological crying after subthalamic nucleus stimulation.

PMID- 23868461
TI  - Macromolecular recognition and macroscopic interactions by cyclodextrins.
AB  - Herein macromolecular recognition by cyclodextrins (CDs) is summarized.
      Recognition of macromolecules by CDs is classified as main-chain recognition or
      side-chain recognition. We found that CDs form inclusion complexes with various
      polymers with high selectivity. Polyrotaxanes in which many CDs are entrapped in
      a polymer chain were prepared. Tubular polymers were prepared from the
      polyrotaxanes. CDs were found to recognize side-chains of polymers selectively.
      CD host polymers were found to form gels with guest polymers in water. These gels
      showed self-healing properties. When azobenzene was used as a guest, the gel
      showed sol-gel transition by photoirradiation. When ferrocene was used, redox
      responsive gels were obtained. Macroscopic self-assembly through molecular
      recognition has been discovered. Photoswitchable gel association and dissociation
      have been observed. 

PMID- 23868462
TI  - Type 2 Diabetes Mellitus and Alzheimer's Disease: from physiopathology to
      treatment implications.
AB  - Alzheimer's Disease (AD) is the most common cause of dementia worldwide. Type 2
      Diabetes Mellitus (T2DM) is a disease characterized by insulin resistance (IR)
      and progressive beta cell failure, and affected individuals are at increased risk
      to develop several forms of cognitive dysfunction, including AD. Different
      mechanisms have already been identified linking visceral obesity, IR and AD.
      Insulin resistance is associated with a decrease in glucose uptake by neurons, an
      increase in Amyloid beta production and secretion, in the formation of senile
      plaques, and also in tau protein phosphorylation. Other mechanisms also include a
      decrease in Insulin Degrading Enzyme (IDE) activity and an increase in oxidative
      stress secondary to hyperglycemia. Taken together, these mechanisms suggest that
      drugs used to ameliorate hyperglycemia and IR may also have beneficial effects in
      diabetic patients with AD. Indeed, manuscripts investigating the effects of
      metformin, thiazolinediones, leptin, GLP-1 therapies, insulin and bariatric
      surgery in cognition and AD have been published with very promising results, and
      may indicate an alternative approach for these patients. This article is
      protected by copyright. All rights reserved.

PMID- 23868463
TI  - Cholinesterase activities and behavioral changes in Hypsiboas pulchellus (Anura:
      Hylidae) tadpoles exposed to glufosinate ammonium herbicide.
AB  - In this study, amphibian tadpoles of Hypsiboas pulchellus were exposed to
      herbicide Liberty(r), which contains glufosinate ammonium (GLA), for 48 h to the
      following concentrations: 0 (control), 3.55, 4.74, 6.32, 8.43, 11.25, 15, 20,
      26.6, and 35.5 mg GLA L(-1). Acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) activities, as well as swimming capabilities
      (swimming speed and mean distance) were measured in tadpoles whose concentrations
      displayed survival rates > 85 %. Our results reveal that sublethal concentrations
      of GLA significantly inhibited both AChE and BChE activities in tadpoles with
      respect to the control, showing a concentration-dependent inhibitory effect. The
      highest inhibition percentages of AChE (50.86%) and BChE (53.02%) were registered
      in tadpoles exposed to 15 mg GLA L(-1). At this concentration, a significant
      increase of the swimming speed and mean distance were found in exposed tadpoles
      with respect to the control, as well as a negative and significant correlation
      between swimming speed and BChE activity, thus suggesting that this enzyme
      inhibition is related to an increase in swimming speed. Therefore, exposure of
      tadpoles to GLA in the wild at concentrations similar to those tested here may
      have adverse consequences at population level because neurotransmission and
      swimming performance are essential for tadpole performance and survival.

PMID- 23868465
TI  - Tracking 3D picometer-scale motions of single nanoparticles with high-energy
      electron probes.
AB  - We observed the high-speed anisotropic motion of an individual gold nanoparticle
      in 3D at the picometer scale using a high-energy electron probe. Diffracted
      electron tracking (DET) using the electron back-scattered diffraction (EBSD)
      patterns of labeled nanoparticles under wet-SEM allowed us to super-accurately
      measure the time-resolved 3D motion of individual nanoparticles in aqueous
      conditions. The highly precise DET data corresponded to the 3D anisotropic log
      normal Gaussian distributions over time at the millisecond scale. 

PMID- 23868464
TI  - Cost-utility analysis of deferiprone for the treatment of beta-thalassaemia
      patients with chronic iron overload: a UK perspective.
AB  - BACKGROUND: Patients with beta-thalassaemia major experience chronic iron
      overload due to regular blood transfusions. Chronic iron overload can be treated
      using iron-chelating therapies such as desferrioxamine (DFO), deferiprone (DFP)
      and deferasirox (DFX) monotherapy, or DFO-DFP combination therapy. OBJECTIVES:
      This study evaluated the relative cost effectiveness of these regimens over a 5
      year timeframe from a UK National Health Service (NHS) perspective, including
      personal and social services. METHODS: A Markov model was constructed to evaluate
      the cost effectiveness of the treatment regimens over 5 years. Based on published
      randomized controlled trial evidence, it was assumed that all four treatment
      regimens had a comparable effect on serum ferritin concentration (SFC) and liver
      iron concentration (LIC), and that DFP was more effective for reducing cardiac
      morbidity and mortality. Published utility scores for route of administration
      were used, with subcutaneously administered DFO assumed to incur a greater
      quality of life (QoL) burden than the oral chelators DFP and DFX. Healthcare
      resource use, drug costs (2010/2011 costs), and utilities associated with adverse
      events were also considered, with the effect of varying all parameters assessed
      in sensitivity analysis. Incremental costs and quality-adjusted life-years
      (QALYs) were calculated for each treatment, with cost effectiveness expressed as
      incremental cost per QALY. Assumptions that DFP conferred no cardiac morbidity,
      mortality, or morbidity and mortality benefit were also explored in scenario
      analysis. RESULTS: DFP was the dominant strategy in all scenarios modelled,
      providing greater QALY gains at a lower cost. Sensitivity analysis showed that
      DFP dominated all other treatments unless the QoL burden associated with the
      route of administration was greater for DFP than for DFO, which is unlikely to be
      the case. DFP had >99 % likelihood of being cost effective against all
      comparators at a willingness-to-pay threshold of L20,000 per QALY. CONCLUSIONS:
      In this analysis, DFP appeared to be the most cost-effective treatment available
      for managing chronic iron overload in beta-thalassaemia patients. Use of DFP in
      these patients could therefore result in substantial cost savings.

PMID- 23868466
TI  - "Homeostatic hitchhiking": a mechanism for the evolutionary retention of complex
      adaptations.
AB  - The complexity of organismal organization channels and accommodates novel genomic
      and developmental modifications. Here, I extend this perspective to suggest that
      emergent processes that dominate homeostasis-co-option, re-use, and recombination
      of accumulated elements-can create configurations and dependencies among these
      elements that strongly reduce the number of evolutionary steps needed for the
      evolution of precise novel adaptations. Evolutionary retention and environmental
      matching of such configurations are further facilitated when they include
      elements of homeostasis that are responsive to particular environmental cues. I
      apply this perspective to the study of evolution of sex-biased egg-laying in
      birds, a phenomenon that combines precision, complexity, context-dependency, and
      reversibility. I show that homeostatic hitchhiking can overcome the main
      difficulty in the evolution of this adaptation-the perceived necessity of de novo
      co-evolution of oogenesis, sex-determination, and order of ovulation in each
      environmental context-something that would require unrealistic expectations of
      evolutionary rates and population sizes and is not a desirable outcome for a
      process that needs to retain substantial environmental sensitivity. First, I
      explain the rationale behind the homeostatic-hitchhiking hypothesis and outline
      its predictions specifically for studies of sex-bias in order of egg-laying.
      Second, I show that a combination of self-regulatory and emergent processes and
      ubiquitous re-use of conserved growth factors make oogenesis particularly
      amendable to homeostatic hitchhiking. Third, I review empirical evidence for this
      mechanism in the rapid evolution of adaptive sex-biased order of egg-laying that
      accompanied colonization of North America by the house finch (Carpodacus
      mexicanus). 

PMID- 23868467
TI  - Testing the red herring hypothesis on an aggregated level: ageing, time-to-death
      and care costs for older people in Sweden.
AB  - In this paper we test the 'red herring' hypothesis for expenditures on long-term
      care (LTC). The main contribution of this paper is to assess the 'red herring'
      hypothesis by using the probability of dying as a measure for time-to-death
      (TTD). In addition, we implement models that allow for age-specific TTD effects
      on LTC utilization as well as sex-specific effects. We also focus on total,
      institutional and domiciliary LTC separately. For our analysis we use high
      quality administrative data from Sweden. Our analysis is based on fixed effects
      estimates. We use our findings to project future LTC expenditures and show that,
      although TTD is a relevant predictor, age itself remains the main driver of LTC
      expenditures. 

PMID- 23868469
TI  - A molecular perspective on nonaqueous biocatalysis: contributions from simulation
      studies.
AB  - The technological value of nonaqueous enzymology has been recognized for more
      than thirty years. A detailed understanding of the molecular determinants of
      enzyme behaviour in nonaqueous media is essential to explore their potential.
      Computer simulations have provided valuable contributions to this field, having
      elucidated how the solvent affects the structural and dynamic properties of
      enzymes, as well as their activity and enantioselectivity. They have also helped
      to shed light on the effect of hydration and the role of counterions. In this
      perspective, we describe the major challenges and achievements of molecular
      simulations of enzymes in different types of nonaqueous solvents, including
      organic solvents, ionic liquids and supercritical fluids. 

PMID- 23868468
TI  - Ischemic preconditioning alters the epigenetic profile of the brain from ischemic
      intolerance to ischemic tolerance.
AB  - Ischemic preconditioning is an innate neuroprotective mechanism in which a sub
      injurious ischemic exposure increases the brain's ability to withstand a
      subsequent, normally injurious ischemic insult. Part of ischemic preconditioning
      neuroprotection stems from an epigenetic reprogramming of the brain to a
      phenotype of ischemic tolerance, which results in a gene expression profile
      different from that observed in the non-injured and ischemia-injured brains. Such
      neuroprotective reprograming, activated by ischemic preconditioning, requires
      specific changes in DNA accessibility coordinated with activation of
      transcriptional activator and repressor proteins, which allows for expression of
      specific neuroprotective proteins despite a general repression of gene
      expression. In this review we examine the effects of injurious ischemia and
      ischemic preconditioning on the regulation of DNA methylation, histone post
      translational modifications, and non-coding RNA expression. There is increasing
      interest in the role of epigenetics in disease pathobiology, and whether and how
      pharmacological manipulation of epigenetic processes may allow for ischemic
      neuroprotection. Therefore, a better understanding of the epigenomic determinants
      underlying the modulation of gene expression that lead to ischemic tolerance or
      cell death offers the promise of novel neuroprotective therapies that target
      global reprograming of genomic activity versus individual cellular signaling
      pathways. 

PMID- 23868470
TI  - Aryl-phosphonate lanthanide complexes and their fluorinated derivatives:
      investigation of their unusual relaxometric behavior and potential application as
      dual frequency 1H/19F MRI probes.
AB  - A series of low molecular weight lanthanide complexes were developed that have
      high (1)H longitudinal relaxivities (r1) and the potential to be used as dual
      frequency (1)H and (19)F MR probes. Their behavior was investigated in more
      detail through relaxometry, pH-potentiometry, luminescence, and multinuclear NMR
      spectroscopy. Fitting of the (1)H NMRD and (17)O NMR profiles demonstrated a very
      short water residence lifetime (<10 ns) and an appreciable second sphere effect.
      At lower field strengths (20 MHz), two of the complexes displayed a peak in r1
      (21.7 and 16.3 mM(-1)  s(-1)) caused by an agglomeration, that can be disrupted
      through the addition of phosphate anions. NMR spectroscopy revealed that at least
      two species are present in solution interconverting through an intramolecular
      binding process. Two complexes provided a suitable signal in (19)F NMR
      spectroscopy and through the selection of optimized imaging parameters, phantom
      images were obtained in a MRI scanner at concentrations as low as 1 mM. The
      developed probes could be visualized through both (1)H and (19)F MRI, showing
      their capability to function as dual frequency MRI contrast agents.

PMID- 23868471
TI  - Glue versus suture fixation of mesh during open repair of inguinal hernias: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Glue fixation of mesh has been explored for some time as a strategy
      for reducing postoperative chronic groin pain. Previous studies have come to
      different conclusions about the superiority of one method over another. We
      conducted a meta-analysis of randomized control trials comparing the performance
      of glue versus suture fixation of mesh in open inguinal hernioplasty. METHODS:
      Studies published up to November 2012 were searched using PubMed, EMBASE,
      MEDLINE, Cochrane Library, and the international standard randomised controlled
      trials number (ISRCTN) register. Mean differences (MDs) were derived from
      secondary continuous outcomes and pooled risk ratios (RRs) for categoric
      outcomes. Meta-analysis was conducted utilizing the random-effects and fixed
      effects models as appropriate. RESULTS: Ten randomized controlled studies were
      selected, with a total of 1,623 patients. Glue fixation for open inguinal
      hernioplasty reduced chronic groin pain (RR 0.46, 95 % confidence interval (CI)
      0.22-0.97), hematoma (RR 0.56, 95 % CI 0.34-0.90), acute postoperative pain (MD 
      7.92, 95 % CI, -13.17 to -2.66), and time taken to return to normal activities
      (MD -1.39, 95 % CI, -2.58 to -0.21). There was no evidence of an increase in
      adverse outcomes including recurrence with glue fixation (RR 0.83, 95 % CI 0.30
      2.35). CONCLUSIONS: Glue fixation of mesh for open inguinal hernioplasty is
      superior in many outcomes including the reduction of chronic groin pain. Glue
      fixation was not associated with an increased risk of hernia recurrence.

PMID- 23868473
TI  - Chemoenzymatic synthesis of the immunoglobulin domain of Tim-3 carrying a complex
      type N-glycan by using a one-pot ligation.

PMID- 23868472
TI  - Retinoic acid receptor alpha is associated with tamoxifen resistance in breast
      cancer.
AB  - About one-third of oestrogen receptor alpha-positive breast cancer patients
      treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic
      acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass
      spectrometry-based proteomics, we show that retinoic acid receptor alpha protein
      networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen
      resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha
      protein levels also correlate with reduced relapse-free survival in oestrogen
      receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen
      solely. A similar retinoic acid receptor alpha expression pattern is seen in a
      comparable independent patient cohort. An oestrogen receptor alpha and retinoic
      acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells
      have increased sensitivity to retinoic acid receptor alpha ligands and are less
      sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data
      indicate that retinoic acid receptor alpha may be a novel therapeutic target and
      a predictive factor for oestrogen receptor alpha-positive breast cancer patients
      treated with adjuvant tamoxifen. 

PMID- 23868474
TI  - The equipoise of perioperative anticoagulation management: a Canadian cross
      sectional survey.

PMID- 23868475
TI  - Lessons learned from the CDC's Colorectal Cancer Screening Demonstration Program.
AB  - This report briefly summarizes 13 articles in this dedicated supplement to Cancer
      documenting the full implementation and evaluation of CDC's Colorectal Cancer
      Screening Demonstration Program (CRCSDP). The supplement includes 3 articles that
      describe clinical and quality outcomes; 2 articles that describe programmatic and
      clinical costs; 3 that were based on a multiple case study, using qualitative
      methods to describe the overall implementation experience of this initiative; and
      4 articles written by and about individual program sites. The comprehensive,
      multi-methods evaluation conducted alongside the program produced many important
      lessons regarding the design, start-up, and implementation of colorectal cancer
      screening in this high-need population, and paved the way for the CDC to
      establish a larger, population-based colorectal cancer control initiative,
      broadly aligned with expectations of the Patient Protection and Affordable Care
      Act through its population-based emphasis on using a health systems approach to
      increase colorectal cancer screening. Cancer 2013;119(15 suppl):2817-9. (c) 2013
      American Cancer Society. 

PMID- 23868476
TI  - Clinical outcomes from the CDC's Colorectal Cancer Screening Demonstration
      Program.
AB  - BACKGROUND: Colorectal cancer remains the second leading cause of cancer-related
      deaths among US men and women. Screening rates have been slow to increase, and
      disparities in screening remain. METHODS: To address the disparity in screening
      for this high burden but largely preventable disease, the Centers for Disease
      Control and Prevention (CDC) designed and established a 4-year Colorectal Cancer
      Screening Demonstration Program (CRCSDP) in 2005 for low-income, under-insured or
      uninsured men and women aged 50 to 64 years in 5 participating US program sites.
      In this report, the authors describe the design of the CRCSDP and the overall
      clinical findings and screening test performance characteristics, including the
      positive fecal occult blood testing (FOBT) rate; the rates of polyp, adenoma, and
      cancer detection with FOBTs and colonoscopies; and the positive predicative value
      for polyps, adenomas, and cancers. RESULTS: In total, 5233 individuals at average
      risk and increased risk were screened for colorectal cancer across all 5 sites,
      including 44% who underwent screening FOBT and 56% who underwent screening
      colonoscopy. Overall, 77% of all individuals screened were women. The FOBT
      positivity rate was 10%. Results from all screening or diagnostic colonoscopies
      indicated that 75% had negative results and required a repeat screening
      colonoscopy in 10 years, 16% had low-risk adenomas and required surveillance
      colonoscopy in 5 to 10 years, 8% had high-risk adenomas and required surveillance
      colonoscopy in 3 years, and 0.6% had invasive cancers. CONCLUSIONS: This report
      documents the successes and challenges in implementing the CDC's CRCSDP and
      describes the clinical outcomes of this 4-year initiative, the patterns in
      program uptake and test choice, and the comparative test performance
      characteristics of FOBT versus colonoscopy. Patterns in final outcomes from the
      follow-up of positive screening tests were consistent with national registry
      data.

PMID- 23868477
TI  - Assessing screening quality in the CDC's Colorectal Cancer Screening
      Demonstration Program.
AB  - BACKGROUND: Gaps in screening quality in community practice have been well
      documented. The authors examined recommended indicators of screening quality in
      the Centers for Disease Control and Prevention's Colorectal Cancer Screening
      Demonstration Program (CRCSDP), which provided colorectal cancer screening and
      diagnostic services between 2005 and 2009 for asymptomatic, low-income,
      underinsured, or uninsured individuals at 5 sites around the United States.
      METHODS: For each client screened in the CRCSDP, a standardized set of colorectal
      cancer clinical data elements was collected. Data regarding client age, screening
      history, risk level, screening test indication, results, and recommendation for
      the next test were analyzed. For colonoscopies, data were analyzed regarding
      whether the cecum was reached, bowel preparation was adequate, and identified
      lesions were completely removed. RESULTS: Overall, 53% of the fecal occult blood
      tests (FOBTs) (2295 tests) distributed were completed and returned. At the 2
      sites with adequate numbers of FOBTs, 77% and 97%, respectively, of clients with
      positive results received follow-up colonoscopies. Site-specific cecal intubation
      rates ranged from 90% to 98%. Adenoma detection rates were 32% for men and 21%
      for women. For approximately one-third of colonoscopies, the recommended interval
      to the next test was shorter than recommended by national guidelines. At some
      sites, endoscopists failed to report on the adequacy of bowel preparation and
      completeness of polyp removal. CONCLUSIONS: Cecal intubation rates and adenoma
      detection rates met recommended levels. The authors identified the need for
      improvements in the follow-up of positive FOBTs, documentation of important
      elements in colonoscopy reports, and recommendations for rescreening or
      surveillance intervals after colonoscopy. Monitoring quality indicators is
      important to improve screening quality.

PMID- 23868478
TI  - Delivering colonoscopy screening for low-income populations in Suffolk County:
      strategies, outcomes, and benchmarks.
AB  - BACKGROUND: Current and pending legislation provides colorectal cancer screening
      reimbursement for previously uninsured populations. Colonoscopy is currently the
      screening method most frequently recommended by physicians for insured patients.
      The experience of the SCOPE (Suffolk County Preventive Endoscopy) demonstration
      project (Project SCOPE) at Stony Brook University Medical Center provides a model
      for delivering colonoscopy screening to low-income populations to meet
      anticipated increasing demands. METHODS: Project SCOPE, based in the Department
      of Preventive Medicine, featured internal collaboration with the academic medical
      center's large gastroenterology practice and external collaboration with the
      Suffolk County Department of Health Services' network of community health
      centers. Colonoscopies were performed by faculty gastroenterologists or
      supervised fellows. Measures of colonoscopy performance were compared with
      quality indicators and differences between faculty and supervised fellows were
      identified. RESULTS: During a 40-month screening period, 800 initial
      colonoscopies were performed. Approximately 21% of women screened were found to
      have adenomatous polyps compared with 36% of men. Five cancers were detected. The
      majority of the population screened (70%) were members of minority populations.
      African American individuals had a higher percentage of proximally located
      adenomas (78%) compared with white individuals (65%) and Hispanics (49%), based
      on the location of the most advanced lesion. Hispanic individuals had a 36% lower
      risk of adenomas compared with white individuals. Performance measures including
      the percentage of procedures with adequate bowel preparation, cecum reached,
      scope withdrawal time, and adenoma detection rate met quality benchmarks when
      performed by either faculty or supervised fellows. CONCLUSIONS: Project SCOPE's
      operational strategies demonstrated a feasible method for an academic medical
      center to provide high-quality screening colonoscopy for low-income populations.

PMID- 23868479
TI  - Outpatient colonoscopy complications in the CDC's Colorectal Cancer Screening
      Demonstration Program: a prospective analysis.
AB  - BACKGROUND: To the authors's knowledge, there are few published prospective
      cohort studies of colonoscopy complications in patients at average risk for
      colorectal cancer who received colorectal cancer screening from a community-based
      program. In this article, the authors report the rate of colonoscopy
      complications in the Centers for Disease Control and Prevention (CDC)'s
      Colorectal Cancer Screening Demonstration Program (CRCSDP), which provided
      colorectal cancer screening to a medically underserved population aged 50 years
      to 64 years for screening, diagnostic follow-up after positive stool blood tests,
      and surveillance purposes. METHODS: Clinical data were collected prospectively
      from 5 community-based colorectal cancer screening programs. Complications were
      identified by reviewing the standardized clinical data and medical complication
      reporting forms submitted by the programs to the CDC. Serious complications were
      defined as conditions or symptoms that resulted in hospital admission within 30
      days after the procedure, including perforation, gastrointestinal bleeding
      requiring or not requiring blood transfusion, cardiopulmonary events,
      postpolypectomy syndrome, excessive abdominal pain, or death. RESULTS: A total of
      3215 individuals underwent 3355 colonoscopies. Of these, 89% of the colonoscopies
      were conducted for screening, 9% were conducted for diagnostic follow-up, and 2%
      were conducted for surveillance purposes. The mean age of the individuals was
      55.9 years. Eight individuals experienced serious complications, for an incidence
      of 2.38 per 1000 colonoscopies. Three patients experienced bowel perforations
      that required surgery, 1 patient was hospitalized for postpolypectomy bleeding, 3
      patients experienced cardiopulmonary events, and 1 patient visited the emergency
      room for excessive abdominal pain and underwent surgery for an identified
      colorectal mass. No deaths were reported. CONCLUSIONS: In the CDC's CRCSDP, in
      which a total of 3215 individuals underwent 3355 colonoscopies, the overall
      incidence of serious complications from colonoscopy was found to be low.

PMID- 23868480
TI  - Costs of planning and implementing the CDC's Colorectal Cancer Screening
      Demonstration Program.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) initiated the
      Colorectal Cancer Screening Demonstration Program (CRCSDP) to explore the
      feasibility of establishing a large-scale colorectal cancer screening program for
      underserved populations in the United States. The authors of the current report
      provide a detailed description of the total program costs (clinical and
      nonclinical) incurred during both the start-up and service delivery (screening)
      phases of the 4-year program. METHODS: Tailored cost questionnaires were
      completed by staff at the 5 CRCSDP sites. Cost data were collected for clinical
      services and nonclinical programmatic activities (program management, data
      collection, and tracking, etc). In-kind contributions also were measured and were
      assigned monetary values. RESULTS: Nearly $11.3 million was expended by the 5
      sites over 4 years, and 71% was provided by the CDC. The proportion of funding
      spent on clinical service delivery and service delivery/patient support comprised
      the largest proportion of cost during the implementation phase (years 2-4). The
      per-person nonclinical cost comprised a substantial portion of total costs for
      all sites. The cost per person screened varied across the 5 sites and by
      screening method. Overall, economies of scale were observed, with lower costs
      resulting from larger numbers of individuals screened. CONCLUSIONS: Programs
      incur substantial variable costs related to clinical services and semivariable
      costs related to nonclinical services. Therefore, programs that serve large
      populations are likely to achieve a lower cost per person.

PMID- 23868481
TI  - Clinical costs of colorectal cancer screening in 5 federally funded demonstration
      programs.
AB  - BACKGROUND: The Centers for Disease Control and Prevention initiated the
      Colorectal Cancer Screening Demonstration Program (CRCSDP) to explore the
      feasibility of establishing a large-scale colorectal cancer (CRC) screening
      program for underserved populations in the United States. The authors of this
      report assessed the clinical costs incurred at each of the 5 participating sites
      during the demonstration period. METHODS: By using data on payments to providers
      by each of the 5 CRCSDP sites, the authors estimated costs for specific clinical
      services and overall clinical costs for each of the 2 CRC screening methods used
      by the sites: colonoscopy and fecal occult blood test (FOBT). RESULTS: Among
      CRCSDP clients who were at average risk for CRC and for whom complete cost data
      were available, 2131 were screened by FOBT, and 1888 were screened by
      colonoscopy. The total average clinical cost per individual screened by FOBT
      (including costs for screening, diagnosis, initial surveillance, office visits,
      and associated clinical services averaged across all individuals who received
      screening FOBT) ranged from $48 in Nebraska to $149 in Greater Seattle. This
      compared with an average clinical cost per individual for all services related to
      the colonoscopy screening ranging from $654 in St. Louis to $1600 in Baltimore
      City. CONCLUSIONS: Variations in how sites contracted with providers and in the
      services provided through CRCSDP affected the cost of clinical services and the
      complexity of collecting cost data. Health officials may find these data useful
      in program planning and budgeting.

PMID- 23868482
TI  - Implementing the CDC's Colorectal Cancer Screening Demonstration Program: wisdom
      from the field.
AB  - BACKGROUND: Colorectal cancer, as the second leading cause of cancer-related
      deaths among men and women in the United States, represents an important area for
      public health intervention. Although colorectal cancer screening can prevent
      cancer and detect disease early when treatment is most effective, few organized
      public health screening programs have been implemented and evaluated. From 2005
      to 2009, the Centers for Disease Control and Prevention funded 5 sites to
      participate in the Colorectal Cancer Screening Demonstration Program (CRCSDP),
      which was designed to reach medically underserved populations. METHODS: The
      authors conducted a longitudinal, multiple case study to analyze program
      implementation processes. Qualitative methods included interviews with 100
      stakeholders, 125 observations, and review of 19 documents. Data were analyzed
      within and across cases. RESULTS: Several themes related to CRCSDP implementation
      emerged from the cross-case analysis: the complexity of colorectal cancer
      screening, the need for teamwork and collaboration, integration of the program
      into existing systems, the ability of programs to use wisdom at the local level,
      and the influence of social norms. Although these themes were explored
      independently from 1 another, interaction across themes was evident. CONCLUSIONS:
      Colorectal cancer screening is clinically complex, and its screening methods are
      not well accepted by the general public; both of these circumstances have
      implications for program implementation. Using patient navigation, engaging in
      transdisciplinary teamwork, assimilating new programs into existing clinical
      settings, and deferring to local-level wisdom together helped to address
      complexity and enhance program implementation. In addition, public health efforts
      must confront negative social norms around colorectal cancer screening.

PMID- 23868483
TI  - Fostering partnerships and program success.
AB  - BACKGROUND: Fostering partnerships was critical to the success of the Colon
      Health Program (CHP) in Greater Seattle. The CHP was built on the Breast and
      Cervical Health Program (BCHP) framework. A replicable system to provide quality
      colorectal screening services for individuals with limited incomes and no health
      insurance was developed. METHODS: Partners were recruited and engaged during 3
      programmatic phases: 1) development and start-up, 2) implementation, and 3)
      sustainability planning. Several tactics were used to develop trust and build
      bridges among the partners and to create an effective work group. RESULTS: The
      partners were critical to developing clinic policies, procedures, and systems to
      increase colorectal screening and improve follow-up; expanding access to
      colonoscopies; and initiating statewide dissemination of training and systems as
      well as policy change. The fecal occult blood test completion rate was 61%, and
      the colonoscopy completion rate was 78%. The colonoscopy navigation system was
      effective with a low "no show" rate (8%). The partners were instrumental in
      helping Washington State obtain funding from the Centers for Disease Control and
      Prevention to continue the CHP statewide. CONCLUSIONS: During implementation, key
      elements for success included: building the project on the successful BCHP
      framework, meticulous training of clinic staff about colorectal cancer and
      screening methods, frequent consultation to identify and solve problems, active
      support of the clinic administration, and the presence of a CHP champion in the
      clinic. Institutionalization of the CHP depended on: assessing progress after the
      first year, documenting experience with the program, disseminating lessons
      learned, engaging new partners, and determining steps to expand the program.

PMID- 23868484
TI  - Clinical case management and navigation for colonoscopy screening in an academic
      medical center.
AB  - BACKGROUND: One of 5 nationally funded Centers for Disease Control and Prevention
      Colorectal Cancer (CRC) Screening Demonstration Programs, Project SCOPE, was
      conducted at an academic medical center and provided colonoscopy screening at no
      cost to underserved minority patients from local community health centers.
      METHODS: Established barriers to CRC screening (eg, financial, language,
      transportation) among the target population were addressed through clinical
      coordination of care by key project staff. The use of a clinician with a patient
      navigator allowed for the performance of precolonoscopy "telephone visits"
      instead of office visits to the gastroenterologist in virtually all patients. The
      clinician elicited information relevant to making screening decisions (eg, past
      medical and surgical history, focused review of systems, medication/supplement
      use, CRC screening history). The patient navigator reduced barriers, including,
      but not limited to, scheduling, transportation, and physical navigation of the
      medical center on the day of colonoscopy. RESULTS: Preprogram preparation was
      vital in laying groundwork for the project, yet enhancements to the program were
      ongoing throughout the screening period. Detailed referral forms from primary
      care physicians, coupled with information obtained during telephone interviews,
      facilitated high colonoscopy completion rates and excellent patient satisfaction.
      Similarly valuable was the employment of a bilingual patient navigator, who
      provided practical and emotional patient support. CONCLUSIONS: Academic medical
      centers can be efficient models for providing CRC screening to disadvantaged
      populations. Coordination of care by a preventive medicine department, directing
      the recruitment, scheduling, prescreening education, and the evaluation and
      preparation of target populations had an overall positive effect on CRC screening
      with colonoscopy among patients from a community health center.

PMID- 23868485
TI  - Collaborating across multiple health care institutions in an urban colorectal
      cancer screening program.
AB  - BACKGROUND: Maryland, excluding Baltimore City, began public health screening for
      colorectal cancer in 2000. Initiating colorectal cancer screening in Baltimore
      City was an objective in the Maryland Comprehensive Cancer Control Plan. The
      Centers for Disease Control and Prevention's (CDC's) funding announcement for the
      "Colorectal Cancer Screening Demonstration Program" (CRCSDP) was seen as a
      potential opportunity for Maryland to begin screening in Baltimore City. METHODS:
      The Maryland Department of Health and Mental Hygiene (DHMH), the American Cancer
      Society, and five Baltimore City Hospitals collaborated to develop the funding
      application and model for the Baltimore City CRCSDP. After receipt of funding,
      between 2005 and September 2009, screening sites collaborated with the DHMH to
      implement the multi-site colorectal cancer screening program in Baltimore City.
      RESULTS: Close collaboration across organizational boundaries enabled the
      funding, formation, and implementation of the CRCSDP in Baltimore City. The
      Baltimore City CRCSDP illustrates the complexity of establishing a functional
      public health screening program. The program overcame expected and unexpected
      fiscal, programmatic, and clinical challenges to successfully perform 709
      colonoscopies screening cycles among 696 people and detect three cancers during
      the 38 months of screening. CONCLUSIONS: Partnerships among the state and local
      health department, the American Cancer Society, and hospitals in Baltimore City
      enabled the implementation of this successful program. Lessons learned from the
      collaborative planning process and the program implementation may facilitate
      similar collaborations in other geographic areas.

PMID- 23868486
TI  - Recruiting patients into the CDC's Colorectal Cancer Screening Demonstration
      Program: strategies and challenges across 5 sites.
AB  - BACKGROUND: In 2005, the Centers for Disease Control and Prevention (CDC) funded
      5 sites as part of the Colorectal Cancer Screening Demonstration Program (CRCSDP)
      to provide colorectal cancer screening to low-income, uninsured, and underinsured
      individuals. Funded sites experienced unexpected challenges in recruiting
      patients for services. METHODS: The authors conducted a longitudinal, qualitative
      case study of all 5 sites to document program implementation, including
      recruitment. Data were collected during 3 periods over the 4-year program and
      included interviews, document review, and observations. After coding and
      analyzing the data, themes were identified and triangulated across the research
      team. Patterns were confirmed through member checking, further validating the
      analytic interpretation. RESULTS: During early implementation, patient enrollment
      was low at 4 of the 5 CRCSDP sites. Evaluators found 3 primary challenges to
      patient recruitment: overreliance on in-reach to National Breast and Cervical
      Cancer Early Detection Program patients, difficulty keeping colorectal cancer
      screening and the program a priority among staff at partnering primary care
      clinics responsible for patient recruitment, and a lack of public knowledge about
      the need for colorectal cancer screening among patients. To address these
      challenges, site staff expanded partnerships with additional primary care
      networks for greater reach, enhanced technical support to primary care providers
      to ensure more consistent patient enrollment, and developed tailored outreach and
      education. CONCLUSIONS: Removing financial barriers to colorectal cancer
      screening was necessary but not sufficient to reach the priority population. To
      optimize colorectal cancer screening, public health practitioners must work
      closely with the health care sector to implement evidence-based, comprehensive
      strategies across individual, environmental, and systems levels of society.

PMID- 23868487
TI  - Developmental milestones across the programmatic life cycle: implementing the
      CDC's Colorectal Cancer Screening Demonstration Program.
AB  - BACKGROUND: In 2005 through 2009, the Centers for Disease Control and Prevention
      (CDC) funded 5 sites to implement a colorectal cancer screening program for
      uninsured, low-income populations. These 5 sites composed a demonstration project
      intended to explore the feasibility of establishing a national colorectal cancer
      screening program through various service delivery models. METHODS: A
      longitudinal, multiple case study was conducted to understand and document
      program implementation processes. Using metaphor as a qualitative analytic
      technique, evaluators identified stages of maturation across the programmatic
      life cycle. RESULTS: Analysis rendered a working theory of program development
      during screening implementation. In early stages, program staff built
      relationships with CDC and local partners around screening readiness, faced real
      world challenges putting program policies into practice, revised initial program
      designs, and developed new professional skills. Midterm implementation was
      defined by establishing program cohesiveness and expanding programmatic reach. In
      later stages of implementation, staff focused on sustainability and formal
      program closeout, which prompted reflection about personal and programmatic
      accomplishments. CONCLUSIONS: Demonstration sites evolved through common
      developmental stages during screening implementation. Findings elucidate ways to
      target technical assistance to more efficiently move programs along their
      maturation trajectory. In practical terms, the time and cost associated with
      guiding a program to maturity may be potentially shortened to maximize return on
      investment for both organizations and clients receiving service benefits.

PMID- 23868488
TI  - Moving forward: using the experience of the CDCs' Colorectal Cancer Screening
      Demonstration Program to guide future colorectal cancer programming efforts.
AB  - BACKGROUND: The Centers for Disease Control and Prevention (CDC) established and
      supported a 4-year Colorectal Cancer Screening Demonstration Program (CRCSDP)
      from 2005 to 2009 for low-income, under- or uninsured men and women aged 50-64 at
      5 sites in the United States. METHODS: A multiple methods evaluation was
      conducted including 1) a longitudinal, comparative case study of program
      implementation, 2) the collection and analysis of client-level screening and
      diagnostic services outcome data, and 3) the collection and analysis of program-
      and patient-level cost data. RESULTS: Several themes emerged from the results
      reported in the series of articles in this Supplement. These included the benefit
      of building on an existing infrastructure, strengths and weakness of both the 2
      most frequently used screening tests (colonoscopy and fecal occult blood tests),
      variability in costs of maintaining this screening program, and the importance of
      measuring the quality of screening tests. Population-level evaluation questions
      could not be answered because of the small size of the participating population
      and the limited time frame of the evaluation. The comprehensive evaluation of the
      program determined overall feasibility of this effort. CONCLUSIONS: Critical
      lessons learned through the implementation and evaluation of the CDC's CRCSDP led
      to the development of a larger population-based program, the CDC's Colorectal
      Cancer Control Program (CRCCP).

PMID- 23868490
TI  - Tilted hexagonal post arrays: DNA electrophoresis in anisotropic media.
AB  - Using Brownian dynamics simulations, we show that DNA electrophoresis in a
      hexagonal array of micron-sized posts changes qualitatively when the applied
      electric field vector is not coincident with the lattice vectors of the array.
      DNA electrophoresis in such "tilted" post arrays is superior to the standard "un
      tilted" approach; while the time required to achieve a resolution of unity in a
      tilted post array is similar to an un-tilted array at a low-electric field
      strengths, this time (i) decreases exponentially with electric field strength in
      a tilted array and (ii) increases exponentially with electric field strength in
      an un-tilted array. Although the DNA dynamics in a post array are complicated,
      the electrophoretic mobility results indicate that the "free path," i.e. the
      average distance of ballistic trajectories of point-sized particles launched from
      random positions in the unit cell until they intersect the next post, is a useful
      proxy for the detailed DNA trajectories. The analysis of the free path reveals a
      fundamental connection between anisotropy of the medium and DNA transport therein
      that goes beyond simply improving the separation device. 

PMID- 23868491
TI  - Hearing loss and the risk of disability pension in Norway: the Hunt Study.
AB  - AIM: The purpose was to explore the possible associations between measured
      hearing thresholds and work related disability pension granted for other medical
      reasons in a Norwegian population. METHOD: This study included 25,537 persons
      from the Nord-Trondelag Health Study (HUNT) aged 20-54 years at baseline in HUNT1
      (1984-1986) who also participated in the follow-up study 11 years later, HUNT2
      (1995-1997) that included a hearing examination. Logistic regression analyses of
      disability pension granted up to 1996 or earlier in life were conducted for men
      and women separately and in two age strata. Effects of low, middle and high
      frequency hearing thresholds were explored, adjusting the effects of each hearing
      frequency for each other. Further adjustment was made for educational level,
      category of work (seven categories) and general health in HUNT1. RESULTS: In all,
      0.4% (16 of 4306) of the disability pensions granted up to 1996 was due to
      hearing related diagnoses. The risk of being granted disability pension up to
      1996 with registered diagnoses not related to hearing loss increased with degree
      of loss of low-frequency hearing in young and middle-aged men and middle-aged
      women (OR 1.72, 95% CI 1.25-2.37; OR 1.16, 95% CI 1.04-1.30; OR 1.11, 95% CI 1.00
      1.23). CONCLUSIONS: Hearing loss diagnoses are rarely reported as main causes in
      disability statistics, however, degree of hearing loss increased the risk of
      being granted with disability pensioning with diagnoses not related to hearing
      loss.

PMID- 23868492
TI  - Clinically diagnosed insomnia and risk of all-cause and diagnosis-specific
      sickness absence: a nationwide Swedish prospective cohort study.
AB  - AIMS: Insomnia is a large health problem. In some prior studies, positive
      associations between insomnia symptoms and sickness absence have been observed.
      There is, however, no previous nationwide cohort study of clinically diagnosed
      insomnia and risk of incident sickness absence. METHODS: Prospective nationwide
      cohort study based on Swedish population-based registers including all 4,956,358
      individuals registered as living in Sweden on 31 December 2004/2005, aged 17-64
      years, not on disability pension, old-age pension or on-going sickness absence.
      Those having insomnia inpatient or outpatient care, defined as having at least
      one admission/specialist visit with a main or secondary diagnosis of disorders of
      initiating and maintaining sleep [insomnias] (ICD-10: G47.0) during 2000/2001
      2005, were compared to those with no such care. All-cause and diagnosis-specific
      incident sickness absence were followed during 2006-2010. Incidence rate ratios
      (IRRs) and 95% confidence intervals (CIs) were estimated by Cox proportional
      hazards regression. RESULTS: In models adjusted for prior sickness absence, socio
      demographic factors and inpatient and specialized outpatient care, associations
      between insomnia and increased risks of all-cause sickness absence (IRR 1.18, 95%
      CI 1.04-1.35) and sickness absence due to mental diagnoses (IRR 1.75, 95% CI 1.36
      2.25) were observed. After further adjustment for insomnia medications these
      associations disappeared. No associations between insomnia and risk of sickness
      absence due to cancer, circulatory or musculoskeletal diagnoses, or injuries,
      were observed. CONCLUSIONS: In this nationwide cohort study, we observed
      increased risks of all-cause sickness absence and sickness absence due to mental
      diagnoses after adjustment for several potential confounders that disappeared
      after further adjustment for insomnia medications.

PMID- 23868493
TI  - Rethinking Woodger's Legacy in the Philosophy of Biology.
AB  - The writings of Joseph Henry Woodger (1894-1981) are often taken to exemplify
      everything that was wrongheaded, misguided, and just plain wrong with early
      twentieth-century philosophy of biology. Over the years, commentators have said
      of Woodger: (a) that he was a fervent logical empiricist who tried to impose the
      explanatory gold standards of physics onto biology, (b) that his philosophical
      work was completely disconnected from biological science, (c) that he possessed
      no scientific or philosophical credentials, and (d) that his work was disparaged 
      if not altogether ignored - by the biologists and philosophers of his era. In
      this paper, we provide the first systematic examination of Woodger's oeuvre, and
      use it to demonstrate that the four preceding claims are false. We argue that
      Woodger's ideas have exerted an important influence on biology and philosophy,
      and submit that the current consensus on his legacy stems from a highly selective
      reading of his works. By rehabilitating Woodger, we hope to show that there is no
      good reason to continue to disregard the numerous contributions to the philosophy
      of biology produced in the decades prior to the professionalization of the
      discipline. 

PMID- 23868494
TI  - New method for the temperature-programmed desorption (TPD) of ammonia experiment
      for characterization of zeolite acidity: a review.
AB  - In this review, a method for the temperature-programmed desorption (TPD) of
      ammonia experiment for the characterization of zeolite acidity and its
      improvement by simultaneous IR measurement and DFT calculation are described.
      First, various methods of ammonia TPD are explained, since the measurements have
      been conducted under the concepts of kinetics, equilibrium, or diffusion control.
      It is however emphasized that the ubiquitous TPD experiment is governed by the
      equilibrium between ammonia molecules in the gas phase and on the surface.
      Therefore, a method to measure quantitatively the strength of the acid site (?H
      upon ammonia desorption) under equilibrium-controlled conditions is elucidated.
      Then, a quantitative relationship between ?H and H0 function is proposed, based
      on which the acid strength ?H can be converted into the H0 function. The
      identification of the desorption peaks and the quantitative measurement of the
      number of acid sites are then explained. In order to overcome a serious
      disadvantage of the method (i.e., no information is provided about the structure
      of acid sites), the simultaneous measurement of IR spectroscopy with ammonia TPD,
      named IRMS-TPD (infrared spectroscopy/mass spectrometry-temperature-programmed
      desorption), is proposed. Based on this improved measurement, Bronsted and Lewis
      acid sites were differentiated and the distribution of Bronsted OH was revealed.
      The acidity characterized by IRMS-TPD was further supported by the theoretical
      DFT calculation. Thus, the advanced study of zeolite acidity at the molecular
      level was made possible. Advantages and disadvantages of the ammonia TPD
      experiment are discussed, and understanding of the catalytic cracking activity
      based on the derived acidic profile is explained. 

PMID- 23868495
TI  - 2D single- or double-layered vanadium oxide nanosheet assembled 3D microflowers:
      controlled synthesis, growth mechanism, and applications.
AB  - A facile one-pot solvent-thermal method was developed to synthesize a unique 3D
      microflower structure assembled from single- or double-layered 2D nanosheets of
      V4O9 (F-VO). Simply by controlling the precursor concentration, yolk-shelled V4O9
      (YS-VO) or bulk V4O9 (B-VO) can be produced instead. The precursor-concentration
      dependent growth mechanism is proposed. The exceptional catalytic/electrochemical
      properties and large specific surface area of F-VO promise a wide range of
      applications. As a proof-of-concept demonstration, we investigate its use in high
      performance supercapacitors (~392 F g(-1)), and for sensitive detection of H2O2
      (with a low detection limit of ~0.1 MUM) and methanol (with a low detection limit
      of ~60 MUM). Furthermore, we show that F-VO greatly outperforms its counterparts
      (YS-VO and B-VO) presumably owing to its unique structure and crystal plane
      orientation.

PMID- 23868496
TI  - Effects of fluoride and cadmium co-exposure on bone in male rats.
AB  - Although cadmium (Cd) and fluoride may both have adverse effects on bone, most
      studies focus on a single agent. In this study, we investigated the effects of
      cadmium and fluoride on bone at a relative low level. Sprague-Dawley male rats
      were assigned randomly into four groups which were given sodium chloride, cadmium
      (50mg/L), and fluoride (20mg/L) alone, or in combination via drinking water. At
      the 12th week, urine, blood, and bone tissues were collected for biomarker assay,
      biomechanical assay, and histological assay. Cadmium had significantly adverse
      effects on bone mineral density, bone biomechanical property, and bone
      microstructure. Fluoride slightly increased vertebral bone mineral density but
      negatively affected bone biomechanical property and bone microstructure. Fluoride
      could reverse the decrease of vertebral bone mineral density caused by cadmium
      but could not improve the damage of bone biomechanical property and
      microstructure caused by cadmium. Tartrate-resistant acid phosphatase 5b levels
      in rats treated with cadmium and fluoride or in combination were 1-2.5 folds
      higher than the control. Our data suggest that low level of fluoride could
      reverse the decrease of vertebral bone mineral density caused by cadmium exposure
      but has no influence on appendicular skeleton damage caused by cadmium. 

PMID- 23868497
TI  - A direct sensitivity comparison between flow-modulated comprehensive 2D and 1D GC
      in untargeted and targeted MS-based experiments.
AB  - The present contribution is focused on the measurement of the analytical
      sensitivity attained in untargeted/targeted MS/MS experiments, performed using
      flow-modulator comprehensive 2D and 1D GC. The comprehensive 2D experiment was
      performed by diverting part of the high flow (circa 80%) to flush the
      accumulation loop (about 28 mL/min) to waste, to reduce the gas flow entering the
      ion source. 1D analyses were performed through: (i) unmodulated and (ii) single
      column applications. An equivalent temperature program was applied in the
      modulated and unmodulated analyses, while a faster one was employed in the single
      column one. In all application types, the (same) triple quadrupole instrument was
      operated in the full-scan and multiple reaction monitoring modes. A genuine sweet
      orange oil and the same sample spiked with 20 phytosanitary compounds were
      employed to reach the research objective. The results highlight the problems
      related to the flow modulation-MS combination. Specifically, it was found that
      sensitivity was on average three to four times higher in unmodulated and
      optimized single-column applications. 

PMID- 23868498
TI  - Status dystonicus due to internal pulse generator depletion in a patient with
      primary generalized dystonia.

PMID- 23868499
TI  - A robust one-compartment fuel cell with a polynuclear cyanide complex as a
      cathode for utilizing H2O2 as a sustainable fuel at ambient conditions.
AB  - A robust one-compartment H2O2 fuel cell, which operates without membranes at room
      temperature, has been constructed by using a series of polynuclear cyanide
      complexes that contain Fe, Co, Mn, and Cr as cathodes, in sharp contrast to
      conventional H2 and MeOH fuel cells, which require membranes and high
      temperatures. A high open-circuit potential of 0.68 V was achieved by using
      Fe3[{Co(III)(CN)6}2] on a carbon cloth as the cathode and a Ni mesh as the anode
      of a H2O2 fuel cell by using an aqueous solution of H2O2 (0.30  M, pH 3) with a
      maximum power density of 0.45 mW cm(-2). The open-circuit potential and maximum
      power density of the H2O2 fuel cell were further increased to 0.78 V and 1.2 mW
      cm(-2), respectively, by operation under these conditions at pH 1. No catalytic
      activity of Co3[{Co(III)(CN)6}2] and Co3[{Fe(III)(CN)6}2] towards H2O2 reduction
      suggests that the N-bound Fe ions are active species for H2O2 reduction. H2O2
      fuel cells that used Fe3[{Mn(III)(CN)6}2] and Fe3[{Cr(III)(CN)6}2] as the cathode
      exhibited lower performance compared with that using Fe3[{Co(III)(CN)6}2] as a
      cathode, because ligand isomerization of Fe3[{M(III)(CN)6}2] into
      (FeM2)[{Fe(II)(CN)6}2] (M = Cr or Mn) occurred to form inactive Fe-C bonds under
      ambient conditions, whereas no ligand isomerization of Fe3[{Co(III)(CN)6}2]
      occurred under the same reaction conditions. The importance of stable Fe(2+)-N
      bonds was further indicated by the high performance of the H2O2 fuel cells with
      Fe3[{Ir(III)(CN)6}2] and Fe3[{Rh(III)(CN)6}2], which also contained stable Fe(2+)
      N bonds. The stable Fe(2+)-N bonds in Fe3[{Co(III)(CN)6}2], which lead to high
      activity for the electrocatalytic reduction of H2O2, allow Fe3[{Co(III)(CN)6}2]
      to act as a superior cathode in one-compartment H2O2 fuel cells.

PMID- 23868501
TI  - Binding of O2 and CO to metal porphyrin anions in the gas phase.

PMID- 23868500
TI  - Immune system: a double-edged sword in cancer.
AB  - OBJECTIVE: The objective of the review is to examine the role of innate and
      adaptive immune cells in cancer. INTRODUCTION: Immune system functions as a host
      defensive mechanism protecting against invading pathogens and transformed cells,
      including cancer. However, a body of research carried out over the last few
      decades has disclosed the unexpected role of immune system in fostering the tumor
      growth. METHODS: A computer-based online search was performed in the PubMed,
      Scopus and Web of Science databases for articles published, concerning natural
      killer (NK) cells, Macrophages, CD4+ and CD8+ T cells with relevance to cancer.
      After finding relevant articles within these search limits, a manual search was
      conducted through the references from these articles. RESULTS AND CONCLUSIONS:
      This review summarizes the role of immune system in Immunosurveillance and
      Immunoediting. It then focused mainly on role of macrophages, regulatory T cells
      (Treg), TH17 cells and on the immunosuppressive mechanisms, which facilitate
      immune evasion of tumor cells. Our results shows that, immune cells, such as CD8+
      cytotoxic T lymphocytes (CTL), CD4+ T helper (TH)1 cells and NK cells along with
      their characteristic cytokine interferon (IFN)-gamma, function as major antitumor
      effector cells. Whereas CD4+TH2 cells, myeloid-derived suppressor cells (MDSCs)
      and their derived cytokines function as dominant tumor-promoting forces. In
      contrast to these cells, macrophages, Treg, and TH17 cells show a dual effect in
      cancer. Thus, it appears that most components of the immune system are
      potentially endowed with dual functions i.e., promoting tumor development on the
      one hand and restraining tumor development on the other and hence immune system
      can be considered as a double-edged sword in cancer.

PMID- 23868502
TI  - Light-harvesting processes in the dynamic photosynthetic antenna.
AB  - We present our perspective on the theoretical basis of light-harvesting within
      the photosynthetic membrane. Far from being a static structure, the
      photosynthetic membrane is a highly dynamic system, with protein mobility playing
      an important role in the damage/repair cycle of photosystem II (PSII), in
      balancing the input of energy between PSI and PSII, and in the photoprotection of
      PSII in response to a sudden excess of illumination. The concept of a
      photosynthetic antenna is illustrated and the state transition phenomenon is
      discussed as an example of purposeful antenna mobility. We discuss fluorescence
      recovery after photo-bleaching as a technique for visualising membrane mobility,
      before introducing light-induced grana membrane reorganisation as an integral
      part of the rapid photoprotective switch in plants. We then discuss current
      theoretical approaches to modelling the energy transfer dynamics of the PSII
      antenna: the atomistic models of intra-complex transfer and the coarse-grained
      approach to the inter-complex dynamics. Finally we discuss the future prospect of
      extending these methods, beyond the static picture of the membrane, to the
      dynamic PSII photosynthetic antenna. 

PMID- 23868503
TI  - Diffusion, spread, and migration of botulinum toxin.
AB  - Botulinum toxin (BoNT) is an acetylcholine release inhibitor and a neuromuscular
      blocking agent used for the treatment of a variety of neurologic and medical
      conditions. The efficacy and safety of BoNT depends on accurate selection and
      identification of intended targets but also may be determined by other factors,
      including physical spread of the molecule from the injection site, passive
      diffusion, and migration to distal sites via axonal or hematogenous transport.
      The passive kinetic dispersion of the toxin away from the injection site in a
      gradient-dependent manner may also play a role in toxin spread. In addition to
      unique properties of the various BoNT products, volume and dilution may also
      influence local and systemic distribution of BoNT. Most of the local and remote
      complications of BoNT injections are thought to be due to unwanted spread or
      diffusion of the toxin's biologic activity into adjacent and distal muscles.
      Despite widespread therapeutic and cosmetic use of BoNT over more than three
      decades, there is a remarkable paucity of published data on the mechanisms of
      distribution and its effects on clinical outcomes. The primary aim of this
      article is to critically review the available experimental and clinical
      literature and place it in the practical context.

PMID- 23868504
TI  - Preparation of polyhedral oligomeric silsesquioxane based hybrid monoliths by
      ring-opening polymerization for capillary LC and CEC.
AB  - A new organic-inorganic hybrid monolith was prepared by the ring-opening
      polymerization of octaglycidyldimethylsilyl polyhedral oligomeric silsesquioxane
      (POSS) with 1,4-butanediamine (BDA) using 1-propanol, 1,4-butanediol, and PEG
      10,000 as a porogenic system. Benefiting from the moderate phase separation
      process, the resulting poly(POSS-co-BDA) hybrid monolith possessed a uniform
      microstructure and exhibited excellent performance in chromatographic
      applications. Neutral, acidic, and basic compounds were successfully separated on
      the hybrid monolith in capillary LC (cLC), and high column efficiencies were
      achieved in all of the separations. In addition, as the amino groups could
      generate a strong EOF, the hybrid monolith was also applied in CEC for the
      separation of neutral and polar compounds, and a satisfactory performance was
      obtained. These results demonstrate that the poly(POSS-co-BDA) hybrid monolith is
      a good separation media in chromatographic separations of various types of
      compounds by both cLC and CEC.

PMID- 23868505
TI  - Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic
      acid microspheres loaded with triamcinolone acetonide on a rabbit model of
      uveitis.
AB  - Conventional treatments of uveitis are not ideal because of the short period of
      therapeutic efficacy. In the present study, biodegradable polylactic-glycolic
      acid microspheres loaded with triamcinolone acetonide (TA) were prepared to
      achieve sustained drug release and their therapeutic efficacy was investigated on
      a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the
      solvent evaporation method and characterized for encapsulation efficiency,
      particle size, morphology and in vitro release. The therapeutic efficacy was
      studied on the rabbit experimental uveitis model based on scoring of the
      inflammation, aqueous leukocyte counting, aqueous protein determination and
      histological examination. The TA-MS exhibited smooth and intact surfaces with an
      average diameter of 50.87 MUm. The drug-loading coefficient and encapsulation
      efficiency were 15.2 +/- 0.6 % and 91.24 +/- 3.77 %, respectively. The drug
      release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The
      change in surface morphology also showed sustained drug release from TA-MS. TA-MS
      exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis
      compared to TA suspension, especially in regard to the inhibition of
      inflammation. The TA-MS had a longer-term therapeutic effect on intraocular
      inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The
      results suggested that TA-MS can be developed as a potential sustained-release
      system for the treatment of uveitis.

PMID- 23868506
TI  - Ret inhibition decreases growth and metastatic potential of estrogen receptor
      positive breast cancer cells.
AB  - We show that elevated levels of Ret receptor are found in different sub-types of
      human breast cancers and that high Ret correlates with decreased metastasis-free
      survival. The role of Ret in ER+ breast cancer models was explored combining in
      vitro and in vivo approaches. Our analyses revealed that ligand-induced Ret
      activation: (i) stimulates migration of breast cancer cells; (ii) rescues cells
      from anti-proliferative effects of endocrine treatment and (iii) stimulates
      expression of cytokines in the presence of endocrine agents. Indeed, we uncovered
      a positive feed-forward loop between the inflammatory cytokine IL6 and Ret that
      links them at the expression and the functional level. In vivo inhibition of Ret
      in a metastatic breast cancer model inhibits tumour outgrowth and metastatic
      potential. Ret inhibition blocks the feed-forward loop by down-regulating Ret
      levels, as well as decreasing activity of Fak, an integrator of IL6-Ret
      signalling. Our results suggest that Ret kinase should be considered as a novel
      therapeutic target in subsets of breast cancer. 

PMID- 23868507
TI  - The use of polyurethane as an elastomer in thermoplastic microfluidic devices and
      the study of its creep properties.
AB  - We report using polyurethane (PU) as an elastomer in microvalves integrated with
      thermoplastic microfluidic devices. Elastomer-based microvalves have been used in
      a number of applications and the elastomer often used is PDMS. Although it is a
      convenient material for prototyping, PDMS has been recognized to possess
      shortcomings such as solvent incompatibility and unfavorable manufacturability.
      We investigated the use of PU as an elastomer to address the challenges. A
      reliable method was developed to bond hybrid materials such as PU and cyclic
      olefin copolymer. The film thickness from 3.5 to 24.5 MUm was studied to identify
      an appropriate thickness of PU films for desirable elasticity in microvalves. We
      integrated PU with thermally actuated, elastomer-based microvalves in
      thermoplastic devices. Valve actuations were demonstrated, and the relationship
      between the valve actuation time and heater power was studied. We compared PU
      with PDMS in terms of their microvalve performance. Valves with PDMS failed to
      function after two weeks since the thermal-sensitive solution evaporated through
      porous PDMS membrane, whereas the same valve with PU functioned properly after
      eight months. In addition, we evaluated the creep and creep recovery of PU, which
      is a common phenomenon of viscoelastic materials and is related to the long-term
      elastic property of PU after prolonged use. 

PMID- 23868508
TI  - The effect of vitamin A supplementation on retinoic acid-related orphan receptor
      gammat (RORgammat) and interleukin-17 (IL-17) gene expression in Avonex-treated
      multiple sclerotic patients.
AB  - The aim of this study was to investigate the role of vitamin A on RORgammat and
      IL-17 gene expression in multiple sclerotic patients. Patients in the vitamin A
      group received 25,000 IU retinyl palmitate per day, while patients in the placebo
      group took one capsule of placebo per day for 6 months. Gene expression was
      measured by real-time PCR at the first and end of the study. The results of this
      study show that vitamin A downregulates IL-17 and RORgammat gene expression. No
      changes in gene expression occurred in the placebo group.

PMID- 23868509
TI  - Perceived effects of organizational downsizing and staff cuts on the stress
      experience: the role of resources.
AB  - In response to global financial pressures, retail companies have introduced
      measures to reduce costs by cutting staff allocations to individual outlets. On
      the basis of interview data from four employees of a large retail organization,
      this paper employs an ideographic case-study approach to illustrate how the
      processes linking job characteristics to job-related strain and well-being (e.g.
      appraisal, action regulation, coping, resource utilization) unfold within four
      individual workers, as they attempt to manage perceived increases in demands
      resulting from staff cuts. We highlight the importance that these employees place
      on their own psychological resources (e.g. self-efficacy) and coping mechanisms
      (e.g. disengagement) in dealing with these changes, as well as how the perceived
      availability or absence of job resources (e.g. social support, decision
      authority, organizational justice) influences their ability to cope with
      increased demands. We use the insights gained from the case studies to illustrate
      the value of integrating multiple theoretical perspectives towards achieving a
      nuanced understanding of the intricacies involved in these experiences and to
      suggest ways in which the coping capacities of individual employees might be
      increased.

PMID- 23868510
TI  - DREB2C acts as a transcriptional activator of the thermo tolerance-related
      phytocystatin 4 (AtCYS4) gene.
AB  - Phytocystatins are proteinaceous inhibitors of cysteine proteases. They have been
      implicated in the regulation of plant protein turnover and in defense against
      pathogens and insects. Here, we have characterized an Arabidopsis phytocystatin
      family gene, Arabidopsis thaliana phytocystatin 4 (AtCYS4). AtCYS4 was induced by
      heat stress. The heat shock tolerance of AtCYS4-overexpressing transgenic plants
      was greater than that of wild-type and cys4 knock-down plants, as measured by
      fresh weight and root length. Although no heat shock elements were identified in
      the 5'-flanking region of the AtCYS4 gene, canonical ABA-responsive elements
      (ABREs) and dehydration-responsive elements (DREs) were found. Transient promoter
      activity measurements showed that AtCYS4 expression was up-regulated in
      unstressed protoplasts by co-expression of DRE-binding factor 2s (DREB2s),
      especially by DREB2C, but not by bZIP transcription factors that bind to ABREs
      (ABFs, ABI5 and AREBs). DREB2C bound to and activated transcription from the two
      DREs on the AtCYS4 promoter although some preference was observed for the GCCGAC
      DRE element over the ACCGAC element. AtCYS4 transcript and protein levels were
      elevated in transgenic DREB2C overexpression lines with corresponding decline of
      endogenous cysteine peptidase activity. We propose that AtCYS4 functions in
      thermotolerance under the control of the DREB2C cascade. 

PMID- 23868511
TI  - Impairments of cells and genomic DNA by environmentally transformed engineered
      nanomaterials.
AB  - Enormous increase in the production of nanomaterials and their growing
      applications in the device technology, biotechnology and biomedical areas suggest
      the need for developing models for predicting the environmental health and safety
      (EHS) risks posed by such nanomaterials. We hypothesize that CdSe quantum dots
      (QDs) and ZnO nanoparticles (NPs) encompassed in liposomes or not and transformed
      by simulated solar UV light can be model systems for studying the environmental
      toxicity of engineered nanomaterials. In this study, human lung epithelial
      adenocarcinoma cells (H1650) are exposed to photoirradiated CdSe QDs or ZnO
      nanopowder included or not in liposomes. The release of cadmium and zinc ions
      from the nanomaterials exposed to solar simulated UV radiation is detected and
      quantified by measuring the steady-state and time resolved fluorescence of the
      metal ion sensor tetracarboxyphenylporphyrin (TCPP) or the commercial Measure iT
      Pd/Cd sensor. Viability of cells treated with nanomaterials exposed to solar
      simulated UV radiation for different durations is measured by MTT assay. Enhanced
      etching of the nanoparticles exposed to solar simulated UV radiation results in
      the release of toxic levels of heavy metal ions, which considerably lower the
      viability of H1650 cells is due to the deactivation of DNA repair enzymes as
      evidenced by the pinching off of nuclear DNA in comet assays and DNA samples in
      electrophoresis. Results from this study highlight the need to obtain not only
      quantitative information about the environmental risks posed by engineered
      nanomaterials but also environment friendly nanomaterials for practical
      applications. 

PMID- 23868512
TI  - Development of blood biomarkers for drug-induced liver injury: an evaluation of
      their potential for risk assessment and diagnostics.
AB  - Drug-induced liver injury (DILI) remains a rare but serious complication in drug
      therapy that is a primary cause of drug failure during clinical trials.
      Conventional biomarkers, particularly the serum transaminases and bilirubin,
      serve as useful indicators of hepatocellular or cholestatic liver injury,
      respectively, but only after substantial and sometimes irreversible tissue
      damage. Ideally, more sensitive biomarkers that respond very early before
      irreversible injury has occurred would offer improved outcomes. Novel biomarkers
      are initially being developed in animal models exposed to intrinsically
      hepatotoxic stimuli. However, the eventual translation to human populations, even
      those with known risk factors that predispose the liver to drug toxicity, would
      be the fundamental goal. Ultimately, some might even be applicable for the early
      identification of individuals predisposed to idiosyncratic hepatotoxicity
      potential. This article reviews recent progress in the discovery and
      qualification of novel biomarkers for DILI and delineates the path to eventual
      utilization for risk assessment. Some major categories of plasma or serum
      biomarkers surveyed include proteins, cytokines, circulating mRNAs, and
      microRNAs. 

PMID- 23868514
TI  - Enhanced open-circuit voltage of PbS nanocrystal quantum dot solar cells.
AB  - Nanocrystal quantum dots (QD) show great promise toward improving solar cell
      efficiencies through the use of quantum confinement to tune absorbance across the
      solar spectrum and enable multi-exciton generation. Despite this remarkable
      potential for high photocurrent generation, the achievable open-circuit voltage
      (Voc) is fundamentally limited due to non-radiative recombination processes in QD
      solar cells. Here we report the highest open-circuit voltages to date for
      colloidal QD based solar cells under one sun illumination. This Voc of 692 +/- 7
      mV for 1.4 eV PbS QDs is a result of improved passivation of the defective QD
      surface, demonstrating Voc(mV)=553Eg/q-59 as a function of the QD bandgap (Eg).
      Comparing experimental Voc variation with the theoretical upper-limit obtained
      from one diode modeling of the cells with different Eg, these results clearly
      demonstrate that there is a tremendous opportunity for improvement of Voc to
      values greater than 1 V by using smaller QDs in QD solar cells.

PMID- 23868513
TI  - Human immunodeficiency virus-associated depression: contributions of immuno
      inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways.
AB  - In the era of greatly improved pharmacological treatment of HIV infection through
      highly active antiretroviral therapy (HAART), HIV patients experience reduced
      viral loads, reduced opportunistic infections, increased CD4+ T cell count, and
      greater life expectancy. Although life expectancy is increased, patients often
      develop neurological disturbances that may persist for long periods, seriously
      jeopardizing quality of life and adherence to the medication protocols of HAART.
      For these reasons, HIV-associated neurological disorders have gained importance
      in both clinical and basic investigations of HIV infection. Depression is the
      most prevalent neuropsychiatric disorder among people living with HIV. In this
      review, we discuss how HIV can predispose infected individuals to depression by
      several interrelated mechanisms. These include inducing chronic elevation of
      cytokines through activation of microglia and astrocytes; decreasing
      monoaminergic function; inducing neurotoxicity, especially in dopaminergic
      neurons; and reducing brain-derived neurotrophic factor. These viral pathways
      interact with psychosocial factors to create the depressive state. HIV depression
      has a great impact on quality of life and implementation of antiretroviral
      therapy, and thus, recognition of these modes of action is significant for
      understanding HIV neuropathology and for selecting modalities for pharmacologic
      treatment. 

PMID- 23868515
TI  - Automated extraction of BI-RADS final assessment categories from radiology
      reports with natural language processing.
AB  - The objective of this study is to evaluate a natural language processing (NLP)
      algorithm that determines American College of Radiology Breast Imaging Reporting
      and Data System (BI-RADS) final assessment categories from radiology reports.
      This HIPAA-compliant study was granted institutional review board approval with
      waiver of informed consent. This cross-sectional study involved 1,165 breast
      imaging reports in the electronic medical record (EMR) from a tertiary care
      academic breast imaging center from 2009. Reports included screening mammography,
      diagnostic mammography, breast ultrasound, combined diagnostic mammography and
      breast ultrasound, and breast magnetic resonance imaging studies. Over 220
      reports were included from each study type. The recall (sensitivity) and
      precision (positive predictive value) of a NLP algorithm to collect BI-RADS final
      assessment categories stated in the report final text was evaluated against a
      manual human review standard reference. For all breast imaging reports, the NLP
      algorithm demonstrated a recall of 100.0 % (95 % confidence interval (CI), 99.7,
      100.0 %) and a precision of 96.6 % (95 % CI, 95.4, 97.5 %) for correct
      identification of BI-RADS final assessment categories. The NLP algorithm
      demonstrated high recall and precision for extraction of BI-RADS final assessment
      categories from the free text of breast imaging reports. NLP may provide an
      accurate, scalable data extraction mechanism from reports within EMRs to create
      databases to track breast imaging performance measures and facilitate optimal
      breast cancer population management strategies.

PMID- 23868516
TI  - Panitumumab in combination with infusional oxaliplatin and oral capecitabine for
      conversion therapy in patients with colon cancer and advanced liver metastases.
      The MetaPan study.
AB  - BACKGROUND: Preoperative chemotherapy improves the outcome in patients with
      colorectal cancer with liver metastases. In the current study, the authors
      evaluated the activity of a conversion treatment with the combination of
      capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in
      patients with unresectable, liver-only, metastatic colon cancer. METHODS:
      Chemotherapy-naive patients with unresectable liver metastases from colon cancer
      with no other metastatic disease sites were enrolled. All patients received
      upfront therapy with XELOX plus panitumumab (P-XELOX) and were reevaluated for
      resectability every 4 cycles. The primary endpoint was the objective response
      rate (ORR). Secondary endpoints were overall survival (OS), progression-free
      survival, the percentage of patients whose disease became radically resectable,
      and the safety of the P-XELOX combination. RESULTS: A total of 49 patients were
      recruited, 35 of whom had wild-type KRAS (wtKRAS) and 14 of whom (who were
      enrolled before study amendment) had unknown (9 patients) or mutated (5 patients)
      KRAS mutational status. Forty-six patients were evaluable for response. After
      conversion P-XELOX therapy, the ORR in the general population was 54%, with 2
      complete responses, 23 partial responses, and 14 cases of stable disease. In
      patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs),
      which allowed 15 patients with initial unresectable liver metastasis to be
      reclassified as having resectable disease. Survival analysis demonstrated a
      median progression-free survival of 8.5 months and a median OS of 21.9 months.
      Patients who underwent surgery were found to have a significantly better OS when
      compared with those who did not undergo surgery (P < .001). Overall, toxicities
      were found to be predictable and manageable, with the most common being
      cutaneous, gastrointestinal, and neurologic toxicities. CONCLUSIONS: Conversion P
      XELOX therapy yields high response and resectability rates for patients with
      metastatic colon cancer with extensive liver involvement.

PMID- 23868517
TI  - A current view of the epigenome in mouse primordial germ cells.
AB  - Primordial germ cells (PGCs) are undifferentiated germ line cells in embryos that
      emerge at early stages of embryonic development, and then differentiate into eggs
      or sperm in gonads to give rise to individuals of successive generations. During
      germ cell development, several dynamic changes in epigenetic modifications
      including DNA methylation and histone modifications occur, and these changes are
      thought to be reprogramming processes that are required for germ cells to confer
      totipotency to the zygote. Initially, the epigenetic status of particular gene
      loci in PGCs was studied, but more recently, genome-wide studies have provided
      more comprehensive views of the PGC epigenome. Mouse PGCs undergo global DNA
      demethylation that starts shortly after PGC specification in early embryos.
      Although the functional importance of global DNA demethylation is not fully
      understood, demethylation of imprinted genes is crucial for erasure of
      methylation-based imprinting, and demethylation of PGC-specific genes is crucial
      for proper transcriptional regulation. PGCs also have unique patterns of histone
      modification, such as hypomethylation of H3K9 and hypermethylation of H3K27, and
      experimental evidence suggests that the unique epigenetic modifications of
      histones are important to the proper development of PGCs.

PMID- 23868518
TI  - Theoretical insights on the effects of mechanical interlocking of secondary
      amines with polyether macrocycles for frustrated-Lewis-pair-type hydrogen
      activation.
AB  - A frustrating environment: It has previously been shown that mechanical
      interlocking of secondary amines with polyether macrocycles enables these amines
      to activate H2 in the presence of B(C6F5)3. Density-functional calculations now
      show that the amine-macrocycle complex both preorganizes a frustrated Lewis pair
      minimum for H2 activation and stabilizes the product through strong hydrogen
      bonds.

PMID- 23868519
TI  - [Methods for endotracheal tube fixation. Results of a survey of intensive care
      nurses].
AB  - There are a wide variety of strategies and methods used in securing and managing
      the oral endotracheal tube and mouth and oral care in German clinical intensive
      care nursing for mechanically ventilated patients. There are no nationally
      recognized guidelines or recommendations on this topic. A survey among intensive
      care nurses identified the most widely used nursing strategies and methods.
      Regarding the results of the survey and international literature findings, the
      commonly used strategies and methods are discussed. Following these discussions,
      there are recommendations for improving nursing care of orally intubated patients
      in intensive care, including the aspects of evidence identified, currently used
      methods and patient needs. Also included are aspects of patient safety, potential
      complications and quality-orientated nursing care within a system having limited
      overall nursing care resources. 

PMID- 23868520
TI  - [Attitude of intensive care specialists toward deceased organ donation in
      Germany. Results of a questionnaire at the 12th Congress of the German
      Interdisciplinary Association for Intensive and Emergency Medicine].
AB  - BACKGROUND: Organ transplantation is the only treatment option for many patients
      with end-organ failure. Due to lack of transplantable organs, patients already on
      the waiting list die every day. The number of organ donors in Germany fell in
      2012 by 12.8 %, reaching its lowest level since 2002. The medical and nursing
      personnel in intensive care units have a key role in the recruitment of potential
      organ donors; therefore, a survey was conducted on this subject. MATERIALS AND
      METHODS: At the 12th Congress of the German Interdisciplinary Association for
      Intensive and Emergency Medicine (DIVI) in December 2012, a point prevalence
      study using a paper-pencil survey was performed. RESULTS: A total of 1045
      questionnaires were analyzed. Of respondents, 81 % favor organ donation in the
      event of their own brain death. The approval rate in the medical profession was
      84 % and 75 % of the nursing profession. Only 45.3 % of the participants (47 %
      physicians, nursing 44 %) had an organ donor card and nearly half (45 %) had
      already confided their opinion towards organ donation to their family or friends.
      The main reasons for a lack of acceptance of organ donation was the concept of
      brain death (40 %), fear of abuse by organ trade (29 %), and the lack of
      integrity of the body after death (11 %). The particularly intense discussion
      about organ donation and transplantation in 2012 resulted in a predominantly
      negative change of attitude in 45 % of respondents. CONCLUSION: The vast majority
      of the intensive care personnel supports organ donation, but less than half of
      the respondents have an organ donor card. The reports of irregularities in the
      organ allocation were scrutinized, but had apparently no significant impact on
      the individual and collective fundamental donor decision.

PMID- 23868521
TI  - Foodborne outbreak of group a streptococcus pharyngitis associated with a high
      school dance team banquet--Minnesota, 2012.
AB  - BACKGROUND: On 20 March 2012, the Minnesota Department of Health (MDH) was
      notified of multiple Facebook postings suggestive of a foodborne outbreak of
      Group A Streptococcus (GAS) pharyngitis occurring among attendees of a high
      school dance team banquet. An investigation was initiated. METHODS: Associations
      between GAS pharyngitis and specific food items were assessed among banquet
      attendees. Pharyngeal swabs were performed on attendees, household contacts, and
      food workers. Patient GAS isolates from clinical laboratories were also obtained.
      Pharyngeal and food specimens were cultured for GAS by the MDH Public Health
      Laboratory. Isolates were further characterized by pulsed-field gel
      electrophoresis (PFGE) and emm typing. RESULTS: Among 63 persons who consumed
      banquet food, 18 primary illnesses occurred, yielding an attack rate of 29%.
      Although no food or beverage items were significantly associated with illness,
      pasta consumption yielded the highest relative risk (risk ratio, 3.56; 95%
      confidence interval, .25-50.6). GAS colonies with indistinguishable PFGE patterns
      corresponding to emm subtype 1.0 were isolated from 5 patients and from leftover
      pasta. The pasta was prepared at home by a dance team member parent; both parent
      and child reported GAS pharyngitis episodes 3 weeks before the banquet.
      CONCLUSIONS: In this foodborne outbreak of GAS pharyngitis, pasta was implicated
      as the vehicle. Recognition of foodborne GAS illness is challenging because
      transmission is typically assumed to occur by respiratory spread; foodborne
      transmission should be considered when clusters of GAS pharyngitis patients are
      encountered. DNA-based typing can reveal potentially epidemiologically related
      isolates during GAS disease outbreaks and facilitate understanding and control of
      GAS disease.

PMID- 23868522
TI  - Posterior hindfoot arthroscopy: a review.
AB  - In recent years, minimally invasive surgery has developed and progressed the
      standard of care in orthopaedics and sports medicine. In particular, the use of
      posterior hindfoot arthroscopy in the treatment of posterior ankle and hindfoot
      injury is increasing rapidly as a means of reducing pain, infection rates, and
      blood loss postoperatively compared with traditional open procedures. In
      athletes, hindfoot arthroscopy has been used effectively in expediting
      rehabilitation and ultimately in minimizing the time lost from competition at
      previous levels. Van Dijk et al were the first to describe the original 2-portal
      technique, which remains the most commonly used by surgeons today and forms the
      basis for this review. The current evidence in the literature supports the use of
      2-portal hindfoot arthroscopy as a safe, primary treatment strategy for symptoms
      of posterior ankle impingement, including resection of os trigonum, treatment of
      flexor hallucis longus and peroneal tendon injury, treatment of osteochondral
      lesions of the ankle, and the resection of subtalar coalitions. In this review,
      we present where possible an evidence-based literature review on the arthroscopic
      treatment of posterior ankle and hindfoot abnormalities. Causes, diagnosis,
      surgical technique, outcomes, and complications are each discussed in turn. 

PMID- 23868523
TI  - Hip arthroscopy for labral tears in workers' compensation: a matched-pair
      controlled study.
AB  - BACKGROUND: Workers' compensation (WC) status has been related to clinical
      outcomes; however, no comparative studies have been performed to assess 2-year
      outcomes between hip arthroscopy patients based on WC status. PURPOSE: To
      evaluate 2-year outcomes of patients receiving WC who underwent hip arthroscopy
      for labral tears and to compare outcomes with those of a matched control group
      not receiving WC. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS:
      During the study period between June 2008 and August 2010, data were collected on
      all patients treated with hip arthroscopy. Inclusion criteria for the study group
      were diagnosis of labral tear and WC status. All patients were assessed pre- and
      postoperatively with 4 patient-reported outcome (PRO) measures: the modified
      Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score
      Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sport-Specific
      Subscales (HOS-SSS). Pain was estimated on the visual analog scale (VAS), and
      satisfaction was measured on a scale from 0 to 10. A matched-pair group of
      patients not associated with WC was selected in a 1:1 ratio according to age
      within 3 years, sex, surgical procedures, and radiographic findings. RESULTS:
      Twenty-one hips were included in each group. Patients with WC status had
      significantly lower preoperative PRO scores for all measures (P < .001). However,
      there was no significant difference between VAS pain scores between the groups.
      Of the WC patients, 86% returned to work at a median 82 days postoperatively. For
      the WC group, the score improvement from preoperative to 2-year follow-up was 46
      to 67.7 for mHHS, 39.3 to 66 for NAHS, 39.7 to 69.5 for HOS-ADL, and 15.3 to 49.8
      for HOS-SSS. For the control group, the score improvement from preoperative to 2
      year follow-up was 67.9 to 85.8 for mHHS, 62.6 to 84.4 for NAHS, 69.8 to 86.9 for
      HOS-ADL, and 41.9 to 73.8 for HOS-SSS. Both groups demonstrated statistically
      significant postoperative improvement in all scores, and the average amount of
      change of preoperative to postoperative scores between the 2 groups was only
      significantly different for the HOS-ADL in the control group (P = .043). However,
      the WC group demonstrated greater improvement in aggregate scores in the HOS-ADL.
      Pain scores decreased from 7 to 3.9 in the WC group and 5.8 to 3.2 in the control
      group and were not significantly different between the groups. Patient
      satisfaction was 6.8 for the WC group and 7.7 for the control group, with no
      significant difference between groups. CONCLUSION: Our study demonstrated that WC
      patients had significantly lower baseline PRO scores when compared with a matched
      pair control group. However, both groups demonstrated statistically significant
      postoperative improvement in all scores. Patients with WC status started and
      ended with lower absolute scores but benefited from arthroscopic intervention for
      hip injuries. While patient and physician expectations may be adjusted
      accordingly, these results may reflect favorably on the use of hip arthroscopy
      for labral tears in the WC population.

PMID- 23868524
TI  - Osteochondral autologous transfer combined with valgus high tibial osteotomy:
      long-term results and survivorship analysis.
AB  - BACKGROUND: Deep osteochondral defects of the medial femoral condyle in young and
      active patients are a serious condition that might lead to early osteoarthritis
      of the knee joint. Concomitant varus malalignment most likely promotes this
      process because of overloading of the medial compartment. Osteochondral
      autologous transfer (OAT) combined with valgus high tibial osteotomy (HTO) might
      therefore be a comprehensive solution to preserve long-term knee function in
      these patients. PURPOSE: To evaluate clinical long-term results and analyze
      survival rates (conversion to knee joint arthroplasty) after combined OAT and
      valgus HTO in young and active patients with symptomatic osteochondral defects of
      the medial femoral condyle and concomitant varus malalignment. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Between 1998 and 2008, combined OAT and
      valgus HTO was performed in 86 patients with deep osteochondral defects of the
      medial femoral condyle and concomitant varus malalignment >2 degrees ; 74
      patients (86%) were available for follow-up evaluation. The mean age of patients
      was 38 years, and the mean follow-up time was 7.5 years. Knee function was
      assessed using the Lysholm score, and pain intensity was measured using the
      visual analog scale (VAS). The survival rates of this combined procedure were
      evaluated. Failure was defined as conversion to knee joint arthroplasty during
      the follow-up period. RESULTS: Adjusted to follow-up time, the Lysholm score
      showed a mean increase of 33 points (95% CI, 27.1-39.4; P < .001) from 40 to 73,
      representing a significant improvement compared with preoperatively. The VAS
      score decreased by a mean of 4.8 points (95% CI, 4.1-5.5; P < .001) from 7.5 to
      2.7, and 93% of the patients were satisfied with the results of the operative
      procedure. Mean survival rates were 95.2% +/- 2.7% at 5 years, 93.2% +/- 3.3% at
      7 years, and 90.1% +/- 4.4% at 8.5 years after surgery. CONCLUSION: Combined OAT
      and valgus HTO is an option to successfully treat patients with deep
      osteochondral defects of the medial femoral condyle and concomitant varus
      malalignment. Significantly improved knee function, decreased pain intensity, and
      a high survivorship rate can be expected up to 8.5 years postoperatively.

PMID- 23868525
TI  - Second-look arthroscopic evaluation of chondral lesions after isolated anterior
      cruciate ligament reconstruction: single- versus double-bundle reconstruction.
AB  - BACKGROUND: Double-bundle (DB) anterior cruciate ligament reconstruction (ACLR)
      has been reported to yield better joint stability than single-bundle (SB)
      reconstruction. Few studies have compared the 2 techniques with regard to
      postoperative articular cartilage changes. HYPOTHESIS: Less cartilage damage
      should occur in the short term after DB ACLR than after SB ACLR. STUDY DESIGN:
      Cohort study; Level of evidence, 2. METHODS: The study included 52 patients (27
      in the DB group and 25 in the SB group) with no chondral or meniscus injury at
      primary ACLR, as confirmed under arthroscopy. Four-strand and 6- to 8-strand
      hamstring autografts, respectively, were used for transtibial SB and 4-tunnel DB
      reconstruction. Each graft was fixed with an EndoButton bioabsorbable
      interference screw and a staple. Cartilage status at 6 identified regions was
      evaluated by second-look arthroscopy and the Outerbridge classification. Other
      assessments at final follow-up included International Knee Documentation
      Committee (IKDC) score, Tegner and Lysholm scores, side-to-side difference on KT
      2000 arthrometer, and range of motion. RESULTS: The mean time from reconstruction
      to second-look arthroscopy was 18.2 and 17.3 months for the DB and SB groups,
      respectively. Both groups had cartilage lesions at the patellofemoral joint
      (patella, 9 vs 13; trochlea, 5 vs 12) and the medial compartment (1 vs 2).
      Significantly less severe lesions were found in the DB group than in the SB group
      (mean grade, 0.33 vs 0.96; P < .05). No significant differences were found
      between the 2 groups in terms of cartilage status at other regions, IKDC score,
      Lysholm score, Tegner score, KT-2000 arthrometer anterior laxity, or range of
      motion. CONCLUSION: Chondral lesions were found postoperatively in both DB and SB
      ACLR groups with hamstring autograft. The DB ALCR led to less cartilage damage at
      the femoral trochlea at short-term follow-up.

PMID- 23868526
TI  - Alcohol-related mortality in deprived UK cities: worrying trends in young women
      challenge recent national downward trends.
AB  - BACKGROUND: Glasgow, the largest city in Scotland, has high levels of deprivation
      and a poor-health profile compared with other parts of Europe, which cannot be
      fully explained by the high levels of deprivation. The 'excess' premature
      mortality in Glasgow is now largely attributable to deaths from alcohol, drugs,
      suicide and violence. METHODS: Alcohol-related mortality in Glasgow from 1980 to
      2011 was examined relative to the equally deprived UK cities of Manchester and
      Liverpool with the aim of identifying differences across the cities, with respect
      to gender, age and birth cohort, that could help explain the 'excess' mortality
      in Glasgow. RESULTS: In the 1980s, alcohol-related mortality in Glasgow was three
      times higher than in Manchester and Liverpool. Alcohol-related mortality
      increased in all three cities over the subsequent three decades, but a sharp rise
      in deaths in the early 1990s was unique to Glasgow. The increase in numbers of
      deaths in Glasgow was greater than in Manchester and Liverpool, but there was
      little difference in the pattern of alcohol-related deaths, by sex or birth
      cohort that could explain the excess mortality in Glasgow. The recent modest
      decrease in alcohol-related mortality was largely experienced by all birth
      cohorts, with the notable exception of the younger cohort (born between 1970 and
      1979): women in this cohort across all three cities experienced disproportionate
      increases in alcohol-related mortality. CONCLUSIONS: It is imperative that this
      early warning sign in young women in the UK is acted on if deaths from alcohol
      are to reduce in the long term.

PMID- 23868528
TI  - Hospitalisation for depressive disorder following unemployment--differentials by
      gender and immigrant status: a population-based cohort study in Sweden.
AB  - BACKGROUND: The association between unemployment and poor mental health in
      general is explained by both causation and selection. The aim was to study
      whether experiencing unemployment was a risk factor for hospitalisation for
      depressive disorder specifically, and whether gender and immigrant status
      modified the hypothesised risk. METHODS: A register-based prospective cohort
      study, 2000-2006, of persons aged 18-64 with a strong connection to the Swedish
      labour market. OUTCOME: hospital admission for a depressive episode; F32 in
      International Classification of Diseases, 10th revision. EXPOSURE: employment
      status. Explanatory variables: gender and immigrant status. Confounders: age
      group, education and marital status. Cox regression models were used to estimate
      HRs with 95% CIs. RESULTS: The cohort comprised 3 284 896 adults, 47.5% women. An
      excess relative risk for hospitalisation was found among those who became
      unemployed (HR=1.94, 95% CI 1.85 to 2.03). Foreign-born women who experienced
      unemployment had the highest relative risk (HR=3.47 95% CI 3.02 to 3.98).
      CONCLUSIONS: Among persons with a strong connection to the labour market
      experiencing unemployment, is a risk factor for hospitalisation for depressive
      disorders. Unemployed foreign-born women had the highest relative risk compared
      with all Swedish born, all foreign-born men and to employed foreign-born women.

PMID- 23868527
TI  - Home and work neighbourhood environments in relation to body mass index: the
      Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Little is known about the neighbourhood characteristics of
      workplaces, the extent to which they are independently and synergistically
      correlated with residential environments, and their impact on health. METHODS:
      This study investigated cross-sectional relationships between home and workplace
      neighbourhood environments with body mass index (BMI) in 1503 working
      participants of the Multi-Ethnic Study of Atherosclerosis with mean age 59.6
      (SD=7.4). Neighbourhood features were socioeconomic status (SES), social
      environment (aesthetic quality, safety and social cohesion) and physical
      environment (walking environment, recreational facilities and food stores)
      derived from census data, locational data on businesses and survey data. Paired t
      tests and correlations compared environments overall and by distance between
      locations. Cross-classified multilevel models estimated associations with BMI.
      RESULTS: Home neighbourhoods had more favourable social environments while
      workplaces had more favourable SES and physical environments. Workplace and home
      measures were correlated (0.39-0.70), and differences between home and workplaces
      were larger as distance increased. Associations between BMI and neighbourhood SES
      and recreational facilities were stronger for home environment (p<=0.05) but did
      not significantly differ for healthy food, safety or social cohesion. Healthy
      food availability at home and work appeared to act synergistically (interaction
      p=0.01). CONCLUSIONS: Consideration of workplace environment may enhance our
      understanding of how place affects BMI.

PMID- 23868529
TI  - Investing in health: is social housing value for money? A cost-utility analysis.
AB  - BACKGROUND: There is a healthy public policy agenda investigating the health
      impacts of improving living conditions. However, there are few economic
      evaluations, to date, assessing value for money. We conducted the first cost
      effectiveness analysis of a nationwide intervention transferring social and
      private tenants to new-build social housing, in Scotland. METHODS: A quasi
      experimental prospective study was undertaken involving 205 intervention
      households and 246 comparison households, over 2 years. A cost-utility analysis
      assessed the average cost per change in health utility (a single score
      summarising overall health-related quality of life), generated via the SF-6D
      algorithm. Construction costs for new builds were included. Analysis was
      conducted for all households, and by family, adult and elderly households; with
      estimates adjusted for baseline confounders. Outcomes were annuitised and
      discounted at 3.5%. RESULTS: The average discounted cost was L18, 708 per
      household, at a national programme cost of L 28.4 million. The average change in
      health utility scores in the intervention group attributable to the intervention
      were +0.001 for all households, +0.001 for family households, -0.04 for adult
      households and -0.03 for elderly households. All estimates were statistically
      insignificant. CONCLUSIONS: At face value, the interventions were not value for
      money in health terms. However, because the policy rationale was the amenity
      provision of housing for disadvantaged groups, impacts extend beyond health and
      may be fully realised over the long term. Before making general value-for-money
      inferences, economic evaluation should attempt to estimate the full social value
      of interventions, model long-term impacts and explicitly incorporate equity
      considerations.

PMID- 23868530
TI  - Highly stable surface modification of hypercrosslinked monolithic capillary
      columns and their application in hydrophilic interaction chromatography.
AB  - A two-step surface modification of poly(styrene-co-vinylbenzyl chloride-co
      divinylbenzene) monolithic stationary phases, including hypercrosslinking and
      thermally initiated surface grafting of [2-(methacryloyloxy)ethyl]dimethyl(3
      sulfopropyl)ammonium hydroxide, has been used to prepare capillary columns for
      the isocratic separation of small polar compounds in hydrophilic interaction
      chromatography (HILIC). The prepared monolithic columns provided a dual retention
      mechanism, combining RP and hydrophilic interaction chromatography, controlled by
      the composition of the mobile phase. By the optimization of the surface grafting
      reaction using response surface methodology, we have found that the grafting time
      is the main synergistic effect controlling the retention of polar compounds in
      HILIC. The prepared monolithic columns achieved long column lifetimes and did not
      lose their separation power following >10,000 injections. Finally,
      hypercrosslinked columns have been used in the 1- and 2D LC of phenolic
      compounds.

PMID- 23868531
TI  - Zeta potential vs apoptotic marker: which is more suitable for ICSI sperm
      selection?
AB  - PURPOSE: Selection of appropriate sperm is considered as a decision making point
      in the ICSI procedure. Canonically, sperm selection is based on morphology and
      motility. Recent advances in this field, have shown that, this procedure can be
      assisted by further selection based on membrane surface charge (Zeta potential)
      and surface apoptotic marker (phosphatidylserine externalization) using magnetic
      activated cell sorter (MACS). Based on the literature, both these procedures
      improve quality of selected sperm population. Therefore, this study aims to
      compare the efficiency of these two procedures. METHODS: Semen samples were
      collected from 36 fertile and infertile (teratozoospermic and /or
      asthenozoospermic) individuals. Sperm DNA fragmentation, protamine deficiency and
      morphology were assessed by TUNEL, CMA3 and papanicolaou staining in unprocessed,
      MACS and Zeta processed samples. RESULTS: Although both MACS and Zeta were able
      to separate a higher percentage of sperm with normal morphology, and lower DNA
      fragmentation and protamine deficiency compared to unprocessed, MACS procedure
      could significantly isolate, a greater percentage of sperm with normal acrosome
      and protamine content compared to Zeta procedure. CONCLUSION: Both MACS and Zeta
      procedures improve the quality of the selected spermatozoa for ICSI. However,
      MACS procedure is more efficient in individuals with severe male factor
      infertility to select sperm with normal acrosome and protamine content but
      concern regarding transfer of MACS beads into the oocyte remains to be resolved.

PMID- 23868532
TI  - Effect of cumulus cell removal 4 h post-insemination on fertilization and embryo
      quality: a prospective randomized sibling-oocyte study.
AB  - PURPOSE: The study was designed to evaluate whether cumulus cell removal 4 h post
      insemination could influence fertilization and embryo quality. METHODS: The study
      included 61couples undergoing standard long down regulation protocol from July
      2011 to May 2012. Sibling oocytes of each patient were randomly assigned to
      either the 4 h group or the 20 group. For the 4 h group, cumulus cells were
      removed 4 h after gamete coincubation; for the 20 group, cumulus cells removal
      was performed 20 h after insemination. Fertilization rate, embryo quality,
      pregnancy rate and implantation rate were assessed. RESULTS: A total of 801
      sibling cumulus-oocyte complexes (COCs) were randomized to the 4 h group (421
      COCs) or 20 h group (380 COCs). There was no difference in the two pronuclei, one
      pronucleus and grade 1-2 embryo rate. Three pronuclei rate was significantly
      higher in the 4 h group compared to the 20 h group (12.6 % vs. 8.2 %, P = 0.041).
      Comparison of embryo transfer cycles in which either embryos from the 4 h group
      or 20 h group were transferred did not reveal any statistically significant
      differences in pregnancy or implantation rates. CONCLUSION: The results of the
      present study indicate that cumulus cell removal 4 h post-insemination may
      increase the percentage of tripronuclear zygotes. However, normal fertilization
      rate, embryo development, clinical pregnancy rate and implantation rates are not
      influenced by the timing of cumulus cell removal.

PMID- 23868533
TI  - Androgen-producing steroid cell ovarian tumor in a young woman and subsequent
      spontaneous pregnancy.
AB  - PURPOSE: To describe the presentation and fertility sparing treatment of a young
      woman found to have a steroid cell tumor not otherwise specified (NOS) and her
      spontaneous pregnancy and delivery shortly after surgery. METHODS: A 20-year-old
      Hispanic female presented with hirsuitism, virilization, and elevated androgen
      levels (testosterone 328 ng/dL) and was wrongly diagnosed with polycystic ovarian
      syndrome. Four months later she sought a second opinion. Her androgens were as
      follows: testosterone level 485 ng/dL, androstenedione 1,738 ng/dL and DHEA 1,459
      ng/dL. She had normal levels of progesterone, estradiol, and DHEA-SO4. On
      transvaginal ultrasound she had a solid-appearing right ovarian mass. She
      underwent fertility sparing surgery with a laparoscopic right oophorectomy.
      RESULTS: Gross and histological pathology confirmed a benign steroid cell tumor
      NOS. She had rapid normalization of all androgens 13 days after surgery. She had
      spontaneous resumption of menses 4 months later. She conceived despite using
      emergency contraception approximately 9 months following surgery and delivered a
      healthy boy at term without complication. CONCLUSION: Prompt evaluation for an
      androgen producing tumor should be performed when testosterone levels are greater
      than 200 ng/dL. Pregnancy following removal of this rare tumor has not previously
      been reported.

PMID- 23868534
TI  - Photoresponsive hydrogen-bonded supramolecular polymers based on a stiff stilbene
      unit.

PMID- 23868535
TI  - No differential DNA methylation of PARK2 in brain of Parkinson's disease patients
      and healthy controls.

PMID- 23868536
TI  - Heme prevents amyloid beta peptide aggregation through hydrophobic interaction
      based on molecular dynamics simulation.
AB  - Heme, which is abundant in hemoglobin and many other hemoproteins, is known to
      play an important role in electron transfer, oxygen transport, regulation of gene
      expression, and many other biological functions. With the belief that the
      aggregation of Abeta peptides forming higher order oligomers is one of the
      central pathological pathways in Alzheimer's disease, the formation of the Abeta
      heme complex is essential as it inhibits Abeta aggregation and protects the
      neurons from degradation. In our studies, conventional molecular dynamics
      simulations were performed on the 1 Abeta + 1 heme and 2 Abeta + 4 hemes system,
      respectively, with the identification of several dominant binding motifs. We
      found that hydrophobic residues of the Abeta peptide have a high affinity to
      interact with heme instead of the histidine residue. We conclude that hydrophobic
      interaction plays a dominant role in the Abeta-heme complex formation which
      indirectly serves to physically prevent Abeta aggregation. 

PMID- 23868537
TI  - Beneficial effect of iron pot cooking on iron status.
AB  - OBJECTIVES: To develop iron rich snacks using locally available iron rich foods
      and analyze their iron content when cooked in iron pots. Further, the efficacy of
      the developed snacks, cooked in iron pots was examined on the hemoglobin status
      of pre-school children through a three month randomized trial. METHODS: Four iron
      rich snacks (mean iron content 2.1mg/serving) were cooked in iron pots and 27
      preschool children (mean age 2.9 +/- 0.9 y, 12 boys) were supplemented with the
      snacks for 4 mo. Anthropometry and dietary intake data were collected.
      Hemoglobin, serum iron and transferrin saturation were assessed. RESULTS: An
      increase of 16.2 % in the iron content was found in the snacks cooked in iron
      pots than cooked in Teflon coated non-stick pots. After 4 mo of supplementation,
      a significant increase of 7.9 % was seen in the hemoglobin of the children.
      CONCLUSION: This pilot study demonstrated that iron rich recipes cooked in iron
      pot have a beneficial effect on iron status of children. Therefore, such food
      based strategies have the potential to alleviate iron deficiency anemia not only
      in children but also in other vulnerable sections of society like in pregnant
      women.

PMID- 23868538
TI  - Lung function and respiratory health at school age in ventilated very low birth
      weight infants.
AB  - OBJECTIVE: To investigate respiratory health and lung function in school-aged
      children without broncho-pulmonary dysplasia (BPD), who were very low birth
      weight (VLBWi) and randomized at birth to high frequency oscillatory ventilation
      (HFOV) or volume guarantee (VG) ventilation for severe respiratory distress
      syndrome (RDS). METHODS: In this observational study, 7-y-old ex-preterm infants
      with severe RDS, randomly assigned at birth to receive assisted/control
      ventilation + VG (Vt = 5 mL/kg, PEEP = 5 cmH2O)(VG group; mean GA 27 +/- 2 wk;
      mean BW 1086 +/- 158 g) or HFOV (HFOV group; mean GA: 27 +/- 2; mean BW: 1090 +/-
      139 g) (both groups were ventilated with Drager Babylog 8000 plus) were recalled.
      Neonatal clinical data and outcome were known. Actual outcomes were investigated
      with an interview; lung function was measured by whole-body plethysmography.
      RESULTS: Twenty five children were studied (VG group, n = 13 vs. HFOV group, n =
      12). There were no differences in anthropometric data, drugs
      (steroids/bronchodilators and antibiotics) or hospital readmission for
      respiratory disorders. Compliance to the test was adequate. The authors found a
      similar obstructive deficit (elevated values: airway resistance (RAW), residual
      volume (RV), total lung capacity (TLC) with near-normal spirometry) in both
      groups suggesting a persistent airflow limitation even in absence of BPD.
      CONCLUSIONS: VLBW infants even in absence of BPD, need long term respiratory
      follow-up, because they frequently show an impairment of lung function,
      independent from initial respiratory support, even if at birth the choice is a
      lung protective approach (e.g., HFOV or VG ventilation).

PMID- 23868539
TI  - Hand hygiene compliance among doctors in a tertiary care hospital of India.

PMID- 23868540
TI  - Multidisciplinary perinatal management of the compromised airway on placental
      support: lessons learned.
AB  - OBJECTIVE: The aims of this study were to review fetal and maternal outcomes
      after management of the compromised perinatal airway via operation on placental
      support or ex utero intrapartum treatment and to discuss implications for future
      management of these complex and rare cases. METHODS: We have presented a
      retrospective case series of 12 neonates requiring airway management on placental
      support at a single tertiary care, academic center. RESULTS: One mother
      experienced significant blood loss. Operative recovery times were unremarkable.
      Eight neonates required airway management due to mass obstruction, two for
      removal of an endotracheal balloon for fetoscopic treatment of congenital
      diaphragmatic hernia, one for laryngeal atresia, and one for severe retrognathia.
      One of our series is an unusual case of management on placental support after
      vaginal delivery. Another child would have ideally been managed on placental
      support, but an extremely short umbilical cord prevented this. Even though the
      airway was secured in all 12 cases, five neonates died in the perinatal period.
      CONCLUSIONS: These procedures have a risk for substantial maternal blood loss.
      Despite excellent rates of success securing the neonatal airway, children who
      require management on placental support still have high mortality. A formalized
      multidisciplinary approach at our institution has enhanced preparedness for these
      cases.

PMID- 23868542
TI  - A flexible joint modeling framework for longitudinal and time-to-event data with
      overdispersion.
AB  - We combine conjugate and normal random effects in a joint model for outcomes, at
      least one of which is non-Gaussian, with particular emphasis on cases in which
      one of the outcomes is of survival type. Conjugate random effects are used to
      relax the often-restrictive mean-variance prescription in the non-Gaussian
      outcome, while normal random effects account for not only the correlation induced
      by repeated measurements from the same subject but also the association between
      the different outcomes. Using a case study in chronic heart failure, we show that
      model fit can be improved, even resulting in impact on significance tests, by
      switching to our extended framework. By first taking advantage of the ease of
      analytical integration over conjugate random effects, we easily estimate our
      framework, by maximum likelihood, in standard software.

PMID- 23868541
TI  - Excellent reliability of the Hamilton Depression Rating Scale (HDRS-21) in
      Indonesia after training.
AB  - INTRODUCTION: The Hamilton Depression Rating Scale (HDRS) is the most widely used
      depression rating scale worldwide. Reliability of HDRS has been reported mainly
      from Western countries. The current study tested the reliability of HDRS ratings
      among psychiatric residents in Indonesia, before and after HDRS training. The
      hypotheses were that: (i) prior to the training reliability of HDRS ratings is
      poor; and (ii) HDRS training can improve reliability of HDRS ratings to excellent
      levels. Furthermore, we explored cultural validity at item level. METHODS:
      Videotaped HDRS interviews were rated by 30 psychiatric residents before and
      after 1 day of HDRS training. Based on a gold standard rating, percentage correct
      ratings and deviation from the standard were calculated. RESULTS: Correct ratings
      increased from 83% to 99% at item level and from 70% to 100% for the total
      rating. The average deviation from the gold standard rating improved from 0.07 to
      0.02 at item level and from 2.97 to 0.46 for the total rating. DISCUSSION: HDRS
      assessment by psychiatric trainees in Indonesia without prior training is
      unreliable. A short, evidence-based HDRS training improves reliability to near
      perfect levels. The outlined training program could serve as a template for HDRS
      trainings. HDRS items that may be less valid for assessment of depression
      severity in Indonesia are discussed.

PMID- 23868543
TI  - Risk prediction for myocardial infarction via generalized functional regression
      models.
AB  - In this paper, we propose a generalized functional linear regression model for a
      binary outcome indicating the presence/absence of a cardiac disease with
      multivariate functional data among the relevant predictors. In particular, the
      motivating aim is the analysis of electrocardiographic traces of patients whose
      pre-hospital electrocardiogram (ECG) has been sent to 118 Dispatch Center of
      Milan (the Italian free-toll number for emergencies) by life support personnel of
      the basic rescue units. The statistical analysis starts with a preprocessing of
      ECGs treated as multivariate functional data. The signals are reconstructed from
      noisy observations. The biological variability is then removed by a nonlinear
      registration procedure based on landmarks. Thus, in order to perform a data
      driven dimensional reduction, a multivariate functional principal component
      analysis is carried out on the variance-covariance matrix of the reconstructed
      and registered ECGs and their first derivatives. We use the scores of the
      Principal Components decomposition as covariates in a generalized linear model to
      predict the presence of the disease in a new patient. Hence, a new semi-automatic
      diagnostic procedure is proposed to estimate the risk of infarction (in the case
      of interest, the probability of being affected by Left Bundle Brunch Block). The
      performance of this classification method is evaluated and compared with other
      methods proposed in literature. Finally, the robustness of the procedure is
      checked via leave-j-out techniques.

PMID- 23868544
TI  - Biology of stress revisited: intracellular mechanisms and the conceptualization
      of stress.
AB  - Application of allostatic theory to stress during the 1990s refocused attention
      on internal responses to a perceived hazard, and the last 20 years has seen
      considerable developments in the biological contexts of stress. Evidence from
      neuroscience now suggests that secretion of the hormone cortisol is not only
      stimulated by the outcomes of cognitive transaction but it also feeds back and
      contributes positively to the cognitive adaptation that is a feature of stress
      resilience. More recently, the operative intracellular mechanisms are beginning
      to be understood and provide an insight into the regulation and maintenance of
      intracellular homeostasis that underpins adaptive change and vulnerability. The
      maintenance or appropriate modulation of intracellular homeostasis usually
      provides a buffering of potential adverse interactions. However, the capacity to
      do so is diminished during chronic stress leading to intracellular and
      subsequently systemic, homeostatic failure and hence maladaptation. This area of
      research seems far removed from cognitive theory, but placing intracellular
      homeostasis at the core of cognitive and biological responses supports the
      concept of stress as a genuinely psycho-biological phenomenon.

PMID- 23868545
TI  - N-heterocyclic carbene catalyzed annulation of benzofuran-2,3-diones and enals: a
      concise synthesis of spiro-bis-lactone.
AB  - The N-heterocyclic carbene catalyzed annulation of benzofuran-2,3-diones and
      enals via homoenolate intermediates is described. The reaction provided a direct
      and efficient method for the synthesis of spiro-bis-lactones. The ketone-carbonyl
      group annulated products and the ester-carbonyl group annulated products can be
      obtained as major products with good yields by convenient catalyst regulation.
      Furthermore, commercially available thiazolium salt can also catalyze this
      reaction with modest yield. 

PMID- 23868546
TI  - Prophylactic and therapeutic effects of a novel granulated formulation of
      Artemisia extract on broiler coccidiosis.
AB  - PURPOSE: Coccidiosis is an important parasitic disease in poultry industry. Owing
      to the development of drug resistance against Eimeria and concerns about drug
      residues, attentions toward the alternative compounds including herbal medicines
      have been increased. This study aimed to examine the prophylactic and therapeutic
      effects of a new formulation derived from Artemisia sieberi extract on avian
      coccidiosis. METHODS: The extract was obtained from A. sieberi using petroleum
      ether, and then, it was formulated into a wet granule. Three hundred and sixty 1
      day-old broilers were divided into six groups, each with three replicates (n =
      20); the first group was chosen as the noninfected control group and the
      remainders were challenged by oral administration of 250,000 oocysts of Eimeria
      tenella per chick on day 21. Group 2 (as nontreated control) received no
      treatment, but group 3 (as prophylactic group) received 0.5 mg/kg artemisinin 10
      days before challenging with E. tenella. However, groups 4, 5, and 6 received 1
      mg/kg artemisinin on the next day and at 24 and 48 h after the challenge,
      respectively, for 5 days. Mortality rate, bloody diarrhea score, lesion score,
      and oocysts per gram (OPG) of feces were used to determine the anticoccidial
      effects of the formulation. RESULTS: The granule significantly (p < 0.05) reduced
      mortality, diarrhea, and lesion score in the treated groups. The OPG output was
      also significantly (p < 0.0001) reduced in the groups that received formulation.
      However, there was no significant difference between the prophylactic and
      therapeutic groups. CONCLUSION: The results suggested that this new formulation
      is a promising herbal medicine that can be used as a prophylactic or therapeutic
      product to control avian coccidiosis.

PMID- 23868547
TI  - Modelling influenza A H5N1 vaccination strategy scenarios in the household
      poultry sector in Egypt.
AB  - Highly pathogenic avian influenza (AI) due to H5N1 virus was first reported in
      Egypt in February 2006; since then, the government has allowed avian influenza
      vaccination in poultry. The present study evaluated the impact of AI vaccination
      in terms of cumulative annual flock immunity (CAFI): the percentage of bird *
      weeks protected by immunity. This evaluation took account of the combined effects
      of vaccination coverage, vaccine efficacy (VE), and different characteristics of
      household poultry production on the effectiveness of the adopted vaccination
      strategy (VS), and provided alternative options for improvement. The evaluation
      used a population and vaccination model that calculates the CAFI. Participatory
      approaches were employed in 21 villages to develop the vaccination and flock
      parameters required for the model. The adopted VS were compared in the model with
      three alternative VS scenarios in terms of the CAFI. Vaccination coverage varied
      among villages but was generally low (between 1 and 48 %; median 14 %). Under the
      adopted VS, the CAFI predicted for the villages ranged from 2 to 31 %. It was
      concluded that despite the enormous effort put into rural household poultry AI
      vaccination by the Egyptian government, village CAFI is unlikely to be maintained
      at the levels required to significantly reduce the virus load and restrict
      transmission. In HPAI-endemic countries that consider AI vaccination as one of
      the disease control options, the high cost of mass AI vaccination campaigns and
      their achievable benefits must be compared with other available control measures,
      which may include targeted vaccination. Achievable vaccination coverage, VE and
      the different characteristics of commercial and household (village) poultry
      production are key parameters determining the feasibility and cost-effectiveness
      of different AI vaccination strategies. 

PMID- 23868548
TI  - Isolation and identification of bovine Brucella isolates from Pakistan by
      biochemical tests and PCR.
AB  - Brucellosis is endemic in bovines in Pakistan. The Brucella species and biovars
      involved, however, are unknown. The objectives of the present study were to
      isolate and characterize brucellae from seropositive milk samples, aborted
      fetuses, and vaginal swabs of cattle and buffaloes which had recently aborted.
      The seropositive milk samples, aborted fetuses, and vaginal swabs of cattle and
      buffaloes were collected from the Potohar Plateau, Pakistan. Isolation of
      brucellae was done on modified Farrell's serum dextrose agar. Isolates were
      characterized by conventional biotyping methods, while molecular typing was done
      by genus (B4/B5) and species-specific (Brucella abortus, Brucella melitensis,
      Brucella ovis, and Brucella suis) polymerase chain reaction (PCR). A total of 30
      isolates were recovered from milk (n = 5), aborted fetuses (n = 13), and vaginal
      swabs (n = 12). Most isolates were from cattle (56.7 %). All of them were
      identified as B. abortus biovar 1 based on conventional biotyping methods and
      genus and species-specific PCR. This preliminary study provides the first report
      on the prevalence of B. abortus biovar 1 in cattle and buffaloes in Pakistan. 

PMID- 23868549
TI  - Evidence of Schmallenberg virus circulation in ruminants in Greece.
AB  - During March 2013, we investigated the presence and the levels of Schmallenberg
      virus (SBV) circulation in three dairy cow herds and three sheep flocks in
      Central Macedonia, Greece. In two cow herds, a high number of abortions had been
      observed during the winter. Six bulk-tank milk samples and 147 individual sera
      were screened for SBV-specific antibodies by ELISA. Positive reactions were
      obtained from 5 out of 6 bulk-tank milk samples, 58 out of 90 sera from the 3 cow
      herds, and 2 sera from 2 of the 3 sheep flocks. Twenty-two ELISA-positive sera
      were tested by serum neutralization test (SNT). SNT confirmed the presence of
      neutralizing antibodies against SBV in all samples tested, with titers ranging
      between 1:32 and >=1:256. No neutralizing antibodies against Akabane virus (AKAV)
      or Shamonda virus (SHAV) were detected, indicating that neutralizing antibodies
      against SBV do not cross react with AKAV or SHAV in SNT. ELISA testing of bulk
      tank milk samples proved to be convenient and reliable. None of the tested sera
      was found positive for SBV by real-time RT-PCR, indicating that the sampling was
      conducted past the viremia stage. This is the first report of SBV circulation in
      Greece. 

PMID- 23868550
TI  - Impact of the HPV-positivity definition on the prognostic value of HPV status in
      patients with locally advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND AND PURPOSE: This study re-evaluated the prognostic value of HPV
      status for loco-regional control (LRC), metastases-free survival (MFS), and
      survival (OS) in patients with locally advanced squamous cell carcinoma of the
      head and neck (SCCHN). A modified definition of HPV positivity was used in the
      current study compared to the authors' previous study. PATIENTS AND METHODS: In
      the previous study of the same 170 patients, a tumor was defined as HPV-positive
      if it showed a positive in situ hybridization result in >=10% of tumor cells
      and/or positive p16 immunostaining. In the current analysis, tumors were
      considered HPV-positive only if they showed positive results for both in situ
      hybridization and p16 immunostaining. In addition to HPV status, the same 11
      potential prognostic factors were investigated for treatment outcomes as in the
      preceding study. RESULTS: In the multivariate analysis of the current study, HPV
      positivity was significantly associated with improved LRC [risk ratio (RR) 9.78;
      p<0.001], MFS (RR 7.17; p=0.008), and OS (RR 6.61; p<0.001). In the previous
      study, HPV positivity was associated with LRC (RR 2.34; p=0.014) and OS (RR 2.19;
      p=0.019), but not with MFS (RR 2.04; p=0.11). CONCLUSIONS: Applying the new
      definition of HPV positivity, the impact of HPV status on the prognosis of
      patients irradiated for locally advanced SCCHN was more prominent than in our
      previous study and associated with all three investigated endpoints.

PMID- 23868551
TI  - [The letters of Ernst Wilhelm Brucke to Rudolf Virchow 1850-1857].
AB  - Rudolf Virchow is one of the most prominent German physician of the nineteenth
      century. Virchow pioneered the modern concept of pathological processes by his
      application of the cell theory to explain the effects of disease in the organs
      and tissues of the body. He emphasized that diseases arose, not in organs or
      tissues in general, but primarily in their individual cells. Moreover, he
      campaigned vigorously for social reforms and contributed to the development of
      anthropology as a modern science. Ernst Wilhelm Brucke was an important
      researcher in most fields of physiology. His works were epoch-making and
      influential for our knowledge of the nature of cells and his optical works made
      the basis for the invention of the eye mirror which was later constructed by
      Helmholtz. He also is also known for his work on the physiology of language. For
      the first time the correspondence between these scientific celebrities is
      published. 

PMID- 23868553
TI  - Glioblastoma survival in the United States improved after Food and Drug
      Administration approval of bevacizumab: a population-based analysis.
AB  - BACKGROUND: Bevacizumab received US Food and Drug Administration approval for use
      in recurrent glioblastoma based on promising radiographic response data, but
      without clear evidence that it prolongs survival. A population-based analysis was
      conducted to determine whether bevacizumab approval was associated with improved
      glioblastoma survival in the United States. METHODS: Surveillance, Epidemiology,
      and End Results (SEER) Program data were used to compare survival of glioblastoma
      patients who died in 2006, 2008 (both prior to approval of bevacizumab), and 2010
      (after approval of bevacizumab). RESULTS: The SEER database contained 1715
      patients with glioblastoma who died in 2006, 1924 who died in 2008, and 1968 who
      died in 2010 who met study inclusion criteria. Median survival was 8 months for
      those who died in 2006, 7 months in 2008, and 9 months in 2010. The difference in
      survival between 2008 (pre-bevacizumab) and 2010 (post-bevacizumab) was highly
      significant. This difference is unlikely to be due to improvements in supportive
      care in this short interval, because there was no significant difference (P =
      .4440) between patients who died in 2006 versus those who died in 2008. Between
      2008 and 2010, a statistically significant improvement in survival was seen in
      all age groups except those patients aged 18 to 39 years. CONCLUSIONS: Patients
      who died of glioblastoma in 2010 had lived with disease significantly longer than
      patients who died in 2008. The most likely explanation for this change is the
      approval and use of bevacizumab for progressive glioblastoma, indicating that at
      a population level, treatment strategies involving bevacizumab prolong survival.

PMID- 23868552
TI  - [Alcohol induced cognitive deficits].
AB  - Previous studies could show a complex relationship between alcohol consumption
      and cognition but also with processes of ageing both social and biological. Acute
      effects of alcohol during intoxication include clinical signs such as excitation
      and reduced inhibition, slurred speech, and increased reaction time but also
      cognitive dysfunction, especially deficits in memory functions. However, these
      cognitive deficits during alcohol intoxication are reversible while patients with
      alcohol addiction and chronic alcohol intake show severe impairments of cognitive
      functions especially deficits in executive functions. Frontal executive
      impairments in these patients include deficits in problem solving, abstraction,
      planning, organizing, and working memory.Additionally, gender specific deficits
      are relevant for the course of the disease and its concomitant health problems
      with female alcoholics showing a higher vulnerability for cognitive dysfunction
      and brain atrophy at earlier stages of alcoholism history. 

PMID- 23868554
TI  - Relationship between maternal parenting and eating self-efficacy in overweight
      children when stressed.
AB  - BACKGROUND: Emotional eating is associated with negative eating habits and
      obesity. Parents may be able to decrease the risk of emotional eating in children
      by promoting greater self-efficacy to engage in healthy eating behaviors. Our
      goal was to determine the relationship between certain parenting behaviors and
      eating self-efficacy (ESE) to consume healthy foods during times of emotional
      stress in a population of overweight/obese children. METHODS: Eighty children
      (60% female; mean BMI percentile = 98.4%; 79.2% White) completed a survey that
      assessed their ESE when stressed, feeling down, or bored. Children also reported
      on mothers' parenting behaviors coded along three factors: acceptance-based
      parenting (AC), psychological control (PC), and firm control (FC). Correlations
      and multiple linear regression models were used for analysis. RESULTS: AC was
      positively correlated with ESE when stressed. PC and FC were inversely correlated
      with ESE when feeling down. In the multivariate regression, only FC was
      significantly inversely associated with ESE when feeling down. CONCLUSION:
      Results suggest that overweight children who perceive their mothers to exhibit
      firm control have lower ESE to make healthy choices when feeling sad. These
      results suggest that pediatric obesity programs should place a stronger focus on
      decreasing firm control behaviors among parents in order to help children engage
      in healthier eating behaviors.

PMID- 23868555
TI  - Energy under-reporting in adults with mood disorders: prevalence and associated
      factors.
AB  - Little is known about relationships of energy under-reporting in mental health
      populations. Using data from a sample of individuals with mood disorders (n =
      97), demographic, food intake and body-related, psychological, lifestyle, and
      condition-specific factors were examined in relationship to energy under
      reporting. More than two-thirds (70%) were considered under-reporters based on
      Goldberg's classifications. Differences were found between energy under-reporters
      and accurate reporters for diet quality, sex, body mass index (BMI), weight
      change after taking psychiatric medications, and for those taking mood
      stabilizers (all p's < 0.05). Regression analyses indicated there was lower
      prevalence of under-reporting as diet quality improved, if individuals
      experienced weight change after taking psychiatric medication, or were females (p
      < 0.05). The prevalence of under-reporting was more than 1.3 times in those
      taking mood stabilizers versus those not taking this psychiatric medication
      [Prevalence ratio (PR) = 1.30, 95% CI 1.01-1.66, p < 0.05]. Further research of
      under-reporting in mental health populations will enable targeted approaches to
      improve accuracy of diet reporting and inferences made about nutrition and mental
      health.

PMID- 23868556
TI  - Doxylamine pharmacokinetics following single dose oral administration in children
      ages 2-17 years.
AB  - To characterize doxylamine pharmacokinetics in children. This study was conducted
      in 41 subjects, ages 2-17 years. Doxylamine succinate doses based on age/weight
      ranged from 3.125 to 12.5 mg. A single oral dose was administered with 2 to 4 oz.
      of water or decaffeinated beverages ~2 hours after a light breakfast. Plasma
      samples were obtained before and for 72 hours after dosing and analyzed for
      doxylamine using HPLC MS/MS. Pharmacokinetic parameters were estimated using non
      compartmental methods and relationships with age were assessed using linear
      regression. Over the fourfold dose range, Cmax was similar while AUC increased
      only 60%, although not statistically significant (P-value = 0.0517). As expected
      due to increasing body size, CLo and Vz /F increased with age. Due to a similar
      increase with age for Clo and Vz /F, no age-related differences in t1/2,z were
      observed (~16 hours). Allometric scaling indicated no maturation related changes
      in CLo ; although Vz /F remained age-dependent, the predicted range decreased
      ~70%. Overall, the single doses were well tolerated. Somnolence was the most
      common reported AE with no apparent differences in incidence noted with age. An
      age/weight dosing nomogram utilizing a fourfold range of doses achieves similar
      Cmax , whereas AUC increases only 60%. 

PMID- 23868557
TI  - Nanochemistry and nanomaterials for photovoltaics.
AB  - Nanochemistry and nanomaterials provide numerous opportunities for a new
      generation of photovoltaics with high solar energy conversion efficiencies at low
      fabrication cost. Quantum-confined nanomaterials and polymer-inorganic
      nanocomposites can be tailored to harvest sun light over a broad range of the
      spectrum, while plasmonic structures offer effective ways to reduce the thickness
      of light-absorbing layers. Multiple exciton generation, singlet exciton fission,
      photon down-conversion, and photon up-conversion realized in nanostructures,
      create significant interest for harvesting underutilized ultraviolet and
      currently unutilized infrared photons. Nanochemical interface engineering of
      nanoparticle surfaces and junction-interfaces enable enhanced charge separation
      and collection. In this review, we survey these recent advances employed to
      introduce new concepts for improving the solar energy conversion efficiency, and
      reduce the device fabrication cost in photovoltaic technologies. The review
      concludes with a summary of contributions already made by nanochemistry. It then
      describes the challenges and opportunities in photovoltaics where the chemical
      community can play a vital role. 

PMID- 23868558
TI  - Rh/Pd catalysis with chiral and achiral ligands: domino synthesis of aza
      dihydrodibenzoxepines.

PMID- 23868560
TI  - Towards a general synthesis of 3-metal-substituted beta-lactams.
AB  - Joining metals and antibiotics: Studies towards a general method for the
      synthesis of beta-lactams that have a metal complex moiety attached to the C3
      position are reported (see scheme). The cis/trans selectivity of the reactions
      ranges from low in complexes containing the alkyne moiety joined directly to the
      cyclopentadienyl ring to complete when the metal moiety is separated from the
      reactive alkyne by an alkynyl-aryl fragment.

PMID- 23868559
TI  - Two-photon voltage imaging using a genetically encoded voltage indicator.
AB  - Voltage-sensitive fluorescent proteins (VSFPs) are a family of genetically
      encoded voltage indicators (GEVIs) reporting membrane voltage fluctuation from
      genetically-targeted cells in cell cultures to whole brains in awake mice as
      demonstrated earlier using 1-photon (1P) fluorescence excitation imaging.
      However, in-vivo 1P imaging captures optical signals only from superficial layers
      and does not optically resolve single neurons. Two-photon excitation (2P)
      imaging, on the other hand, has not yet been convincingly applied to GEVI
      experiments. Here we show that 2P imaging of VSFP Butterfly 1.2 expresssing
      pyramidal neurons in layer 2/3 reports optical membrane voltage in brain slices
      consistent with 1P imaging but with a 2-3 larger DeltaR/R value. 2P imaging of
      mouse cortex in-vivo achieved cellular resolution throughout layer 2/3. In
      somatosensory cortex we recorded sensory responses to single whisker deflections
      in anesthetized mice at full frame video rate. Our results demonstrate the
      feasibility of GEVI-based functional 2P imaging in mouse cortex. 

PMID- 23868561
TI  - Parkinson's disease: is it all in the genes?

PMID- 23868562
TI  - Coping strategies as mediators and moderators between stress and quality of life
      among parents of children with autistic disorder.
AB  - The purpose of this cross-sectional study was to examine coping strategies as
      mediators and moderators between stress and quality of life (QoL) among parents
      of children with autistic disorder. The convenience sample of the study consisted
      of 184 parents of children with autistic disorder. Advanced statistical methods
      for analyses of mediator and moderator effects of coping strategies were used.
      The results revealed that 'accepting responsibility' was the only mediator
      strategy in the relationship between stress and QoL. The results also revealed
      that only 'seeking social support' and 'escape avoidance' were moderator
      strategies in the relationship between stress and QoL. This study is perhaps the
      first to investigate the mediating and moderating effects of coping on QoL of
      parents of children with autistic disorder. Recommendations for practice and
      future research are presented.

PMID- 23868563
TI  - Being confident without seeing: what subjective measures of visual consciousness
      are about.
AB  - Can observers be confident about the accuracy of a discrimination response
      without a visual experience of the stimulus? In a series of five experiments,
      observers performed a masked orientation discrimination task, a masked shape
      discrimination task, or a random-dot motion discrimination task, followed by two
      subjective ratings after each trial, in which participants reported either their
      visual experience of the stimulus or their confidence in being correct. We
      observed that the threshold for ratings of the perception of the stimulus was
      above the threshold for ratings of a decision, that decision ratings outperformed
      stimulus ratings in predicting trial accuracy, and that different decision
      related scales were more strongly associated with other decision-related scales
      than with ratings of stimulus clarity. We propose a taxonomy of subjective
      measures of consciousness that differentiates between subjective measures
      relating to the percept of the stimulus and measures relating to a discrimination
      decision and discuss the relation to type II blindsight. 

PMID- 23868564
TI  - Quantifying temporal ventriloquism in audiovisual synchrony perception.
AB  - The integration of visual and auditory inputs in the human brain works properly
      only if the components are perceived in close temporal proximity. In the present
      study, we quantified cross-modal interactions in the human brain for audiovisual
      stimuli with temporal asynchronies, using a paradigm from rhythm perception. In
      this method, participants had to align the temporal position of a target in a
      rhythmic sequence of four markers. In the first experiment, target and markers
      consisted of a visual flash or an auditory noise burst, and all four combinations
      of target and marker modalities were tested. In the same-modality conditions, no
      temporal biases and a high precision of the adjusted temporal position of the
      target were observed. In the different-modality conditions, we found a systematic
      temporal bias of 25-30 ms. In the second part of the first and in a second
      experiment, we tested conditions in which audiovisual markers with different
      stimulus onset asynchronies (SOAs) between the two components and a visual target
      were used to quantify temporal ventriloquism. The adjusted target positions
      varied by up to about 50 ms and depended in a systematic way on the SOA and its
      proximity to the point of subjective synchrony. These data allowed testing
      different quantitative models. The most satisfying model, based on work by Maij,
      Brenner, and Smeets (Journal of Neurophysiology 102, 490-495, 2009), linked
      temporal ventriloquism and the percept of synchrony and was capable of adequately
      describing the results from the present study, as well as those of some earlier
      experiments. 

PMID- 23868565
TI  - The association of warthin tumor with salivary ductal inclusions in intra and
      periparotid lymph nodes.
AB  - A predominant theory of the much debated histogenesis of Warthin tumor (WT) is
      that it arises from heterotopic salivary ductal inclusions (SDI) in parotid lymph
      nodes (LN). If this were the case, we might expect to see an increased number of
      SDI in the lymph nodes of patients with WT compared to controls. To test this, we
      compared the prevalence of SDI in patients with WT versus those with pleomorphic
      adenoma (PA). Cases of WT and PA were retrieved from the case files of the
      Department of Pathology at the QEII Health Science Centre, Halifax, NS, Canada.
      We then compared the prevalence of SDI in parotid LN between patients diagnosed
      with WT versus PA. 46 WT and 52 PA met our inclusion criteria. WT was
      significantly associated with an older age at surgery (62.5 years vs 50.2 years,
      p = 0.001). 71.7 % of WT and 32.7 % of PA had inclusions in any LN. The presence
      of inclusion is a significant predictor for WT versus PA (p = 0.019). Where
      smoking status was available, 92.5 % of WT patients were smokers/ex-smokers,
      versus. 55.1 % of PA (p = 0.034 for current smokers). Among PA, 44 % of smokers
      had inclusions compared with 22.7 % of non-smokers. SDIs are more frequent in
      parotid LN from patients with WT than PA. The high proportion of smokers among WT
      patients is consistent with prior studies. The results support the hypothesis
      that WT arises from SDIs. Individuals with more SDIs may be predisposed to WT.

PMID- 23868566
TI  - Towards kinetic modeling of genome-scale metabolic networks without sacrificing
      stoichiometric, thermodynamic and physiological constraints.
AB  - Mathematical modeling is an essential tool for the comprehensive understanding of
      cell metabolism and its interactions with the environmental and process
      conditions. Recent developments in the construction and analysis of
      stoichiometric models made it possible to define limits on steady-state metabolic
      behavior using flux balance analysis. However, detailed information on enzyme
      kinetics and enzyme regulation is needed to formulate kinetic models that can
      accurately capture the dynamic metabolic responses. The use of mechanistic enzyme
      kinetics is a difficult task due to uncertainty in the kinetic properties of
      enzymes. Therefore, the majority of recent works considered only mass action
      kinetics for reactions in metabolic networks. Herein, we applied the optimization
      and risk analysis of complex living entities (ORACLE) framework and constructed a
      large-scale mechanistic kinetic model of optimally grown Escherichia coli. We
      investigated the complex interplay between stoichiometry, thermodynamics, and
      kinetics in determining the flexibility and capabilities of metabolism. Our
      results indicate that enzyme saturation is a necessary consideration in modeling
      metabolic networks and it extends the feasible ranges of metabolic fluxes and
      metabolite concentrations. Our results further suggest that enzymes in metabolic
      networks have evolved to function at different saturation states to ensure
      greater flexibility and robustness of cellular metabolism. 

PMID- 23868568
TI  - Comment on "QF-PCR as a substitute for karyotyping of cytotrophoblast for the
      analysis of chorionic villi: advantages and limitations from a cytogenetic
      retrospective audit of 44 727 first-trimester prenatal diagnoses".

PMID- 23868567
TI  - Phrenic nerve stimulation in CRT patients and benefits of electronic lead
      repositioning: the ERACE trial.
AB  - PURPOSE: Despite novel left ventricular (LV) lead technologies, phrenic nerve
      stimulation (PNS) remains an adverse effect observed in many patients with
      cardiac resynchronization therapy (CRT). Beyond anatomic repositioning, modern
      CRT devices allow avoidance of PNS also by software-based adaption of the pacing
      configuration. The Electronic Repositioning With Acuity and Easytrak Leads study
      evaluated the incidence of PNS in a CRT population and examined how often LV lead
      relocation can be avoided by "electronic repositioning" (ER). METHODS: Patients
      who had an indication for implantation of a first CRT defibrillator with the
      option of ER were enrolled. Primary endpoint was the efficiency of ER determined
      by the frequency of PNS with the standard pacing configuration (LV tip to RV
      coil) avoidable by ER. PNS and pacing parameters were evaluated during implant,
      predischarge, and first routine follow-up (FU) using four different pacing
      configurations available by ER. RESULTS: In total, 292 patients were enrolled and
      provided with a transvenous LV lead (82.2 % male, 65.5 +/- 9.2 years old). The
      majority of the population was in NYHA III (84.2 %) with a LV ejection fraction
      of 25.3 +/- 6.8 % and mean QRS width of 155 +/- 27 ms, ischemic cardiomyopathy
      was present in 43.6 %. Median FU was 116 days. In the standard pacing
      configuration, PNS was inducible in 19.0/25.6/24.6 % at implant/predischarge/FU,
      respectively, resulting in 32.2 % of the patients presenting at least once with
      PNS. The safety margin for the standard pacing configuration between LV and PNS
      threshold was <1.0 V at 0.5 ms in 5.6/7.0/5.0 % of the patients, corresponding
      with a total rate of 11.6 % during the FU. In the finally chosen configuration,
      clinically relevant PNS occurred in 1.0/2.2/1.3 %. The four vector configurations
      allowed all but 6 of 292 (2 %) patients to be reprogrammed using ER without
      reoperation. CONCLUSIONS: The incidence of inducible PNS in CRT patients is
      considerable. In this study, PNS could be avoided in the majority of the patients
      by means of electronic repositioning. Thus, the use of ER should be considered
      for CRT patients.

PMID- 23868569
TI  - Defining reference genes for qPCR normalization to study biotic and abiotic
      stress responses in Vigna mungo.
AB  - KEY MESSAGE: Expression of ACT, EF1A; H2A, EF1A, ACT and 18S, TUB showed
      stability under MYMIV, salinity and drought stress, respectively; these are
      recommended as reference genes for qPCR normalization in Vigna mungo. Accurate
      gene expression profiling through qPCR depends on selection of appropriate
      reference gene(s) for normalization. Due to lack of unanimous internal standard,
      suitable constitutively expressed reference genes are selected that exhibit
      stable expression under diverse experimental conditions. In this communication, a
      comparative evaluation of stability among seven V. mungo genes encoding actin
      (ACT), histone H2A (H2A), elongation factor 1-alpha (EF1A), 18S rRNA (18S),
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH), cyclophilin (CYP) and tubulin
      (TUB) under biotic (MYMIV) and abiotic (drought and salinity) stress conditions
      has been attempted. Specificity and amplification efficiency for each primer pair
      were verified; however, cumulative assessment of their accumulated transcripts
      revealed no uniformity. Therefore, individual stability and suitability of these
      seven candidates have been assessed in silico, by two widely used algorithms,
      geNorm and Normfinder. Based on the computed results, high stability was obtained
      for ACT and EF1A during MYMIV stress, while H2A, EFIA and ACT were found to be
      most suitable in salinity stress experiments and TUB and 18S during drought
      treatments. Combinations of ACT/TUB or ACT/EFIA were recommended for their use in
      the pooled analysis, while expression of 18S and CYP showed greater variations
      and therefore considered unsuitable as reference genes. Additionally, precise
      quantification of the target gene VmPRX under these stresses was shown to be a
      function of reference genes' stability, which tends to get affected when
      normalized with the least stable genes. Hence, use of these normalizers will
      facilitate accurate and reliable analyses of gene expression in V. mungo.

PMID- 23868570
TI  - Gender differences in alcohol demand: a systematic review of the role of prices
      and taxes.
AB  - Gender differences in drinking patterns are potentially important for public
      policies, especially policies that rely extensively on higher alcohol taxes and
      prices. This paper presents a systematic review of alcohol prices and gender
      differences in drinking and heavy drinking by adults and young adults. Starting
      with a database of 578 studies of alcohol demand and other outcomes, 15 studies
      are reviewed of adult drinking including discussion of samples, measurement
      issues, econometric models, special variables, and key empirical results. A
      similar discussion is presented for eight studies of drinking by young adults,
      ages 18-26 years. Four conclusions are obtained from the review. First, adult men
      have less elastic demands compared with women. Second, there is little or no
      price response by heavy-drinking adults, regardless of gender. Third, although
      the sample is small, price might be important for drinking participation by young
      adults. Fourth, the results strongly suggest that heavy drinking by young adults,
      regardless of gender, is not easily dissuaded by higher prices. Policy
      implications, primary study limitations, and suggestions for future research are
      discussed.

PMID- 23868571
TI  - A hepatitis C virus NS4B inhibitor suppresses viral genome replication by
      disrupting NS4B's dimerization/multimerization as well as its interaction with
      NS5A.
AB  - Chronic hepatitis C virus (HCV) infection is responsible for severe liver
      diseases including liver cirrhosis and hepatocellular carcinoma. An HCV non
      structural protein 4B (NS4B) plays an essential role in viral RNA genome
      replication by building multi-vesicular structures around endoplasmic reticulum
      membranes. Especially, the second amphipathic helix of NS4B (NS4B-AH2) was shown
      to be essential for this process. By screening compounds against a membrane
      aggregating activity of NS4B-AH2, several anti-HCV replication small molecules
      targeting NS4B-AH2 were discovered. However, little is known about detailed
      molecular mechanism of action for these NS4B-AH2 inhibitors. In this report, we
      provide evidences that NS4B-AH2 is required for NS4B's
      dimerization/multimerization, its proper subcellular localization, as well as its
      interaction with NS5A. More importantly, one of NS4B-AH2 inhibitors called
      "anguizole" was found to be able to disrupt all of these NS4B-AH2-mediated
      biological functions of NS4B. This newly elucidated mechanism of action will
      enable us not only to better understand a central role of NS4B-AH2 in HCV life
      cycle but also to develop a more safe and effective new class of NS4B-AH2
      inhibitors of HCV replication in the future. 

PMID- 23868572
TI  - [Healing by secondary intention after skin cancer surgery on the head and neck].
AB  - Defects resulting from skin cancer surgery of the head and neck can be closed
      with a variety of reconstruction techniques. Primary closure, local flaps and
      skin grafts are commonly used. Besides defect size and anatomic localization, the
      choice of a specific technique also depends on the dermatosurgeon's preference.
      Secondary intention healing often has a bad reputation and is wrongly regarded as
      synonymous with insufficient skills in reconstructive surgery. The indications
      and contraindications for secondary healing in the head and neck area are
      presented and related to different anatomic subunits. 

PMID- 23868573
TI  - Indication for allogeneic stem cell transplantation in Glanzmann's
      thrombasthenia.
AB  - Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder characterized
      by a lack of thrombocyte aggregation due to the absence of thrombocyte
      glycoproteins IIb and alphaIIbbeta3. The role of haematopoietic stem cell
      transplantation (HSCT) in GT remains controversial. However, HSCT offers the only
      curative approach for patients with a severe clinical phenotype. In this review,
      we will discuss the limitation of current status evidence and the specific risk
      of GT, in particular the alloimmunization and refractoriness to thrombocyte
      infusions. 19 successful HSCT in 18 GT type I patients have been reported. Mean
      age at transplantation was 5 years. All patients are still alive. The majority
      received sibling bone marrow transplant with busulfan and cyclophosphamid
      conditioning. GvHD incidence was within the normal range, but 10 patients showed
      alloimmunization of thrombocytes. Median follow up is 25 months. 

PMID- 23868574
TI  - Increase in iodine deficiency disorder due to inadequate sustainability of supply
      of iodized salt in District Solan, Himachal Pradesh.
AB  - Himachal Pradesh is a known endemic area for iodine deficiency disorders. A study
      was conducted in district Solan with the objective of assessing the prevalence of
      iodine deficiency disorders in school-age children. Thirty clusters were selected
      by using the probability-proportionate-to-size cluster sampling methodology.
      Clinical examination of the thyroid of 1898 children in the age-group of 6-12
      years was conducted. Urine and salt samples were collected. The total goiter rate
      was found to be 15.4%. Median urinary iodine excretion level was 62.5 MUg/l. Only
      39% of the salt samples had iodine content of >=15 ppm. Mild iodine deficiency
      was present in the subjects studied. 

PMID- 23868575
TI  - Serum tenascin-C: a novel biomarker for diagnosis and predicting prognosis of
      rheumatic carditis?
AB  - BACKGROUND: Tenascin-C (TnC) is an extracellular matrix glycoprotein that has a
      major role in tissue remodeling. OBJECTIVE: To evaluate the serum TnC level in
      acute rheumatic fever (ARF) and chronic rheumatic heart disease (CRHD) during
      childhood. METHODS: Twenty-five patients with ARF, 25 patients with CRHD and 20
      control subjects were included in the study. The TnC levels were analyzed using
      the enzyme-linked immunosorbent assay method in the ARF group. RESULTS: The TnC
      levels were lower in the acute carditis group compared with the control group (p
      < 0.001). The cut-off level was estimated as 2.08 ng/ml for diagnosing carditis
      with 93.3% sensitivity and 95% specificity. On second analysis, prominent
      decrease was detected in valve insufficiency patients with markedly elevated TnC
      levels. In the CRHD group, TnC level was significantly lower in cases with severe
      valve insufficiency (p < 0.001). CONCLUSIONS: Serum TnC level can be used as a
      new biochemical marker for diagnosis and predicting the prognosis of rheumatic
      carditis.

PMID- 23868577
TI  - Accurate estimation of body surface area in under-5 children with non-edematous
      severe acute malnutrition.
AB  - OBJECTIVE: To determine the accuracy of commonly used body surface area (BSA)
      equations and to devise a new equation for BSA calculation in non-edematous
      severe acute malnourished (NE-SAM) children. METHODS: Children aged between 2
      months and 5 years fulfilling World Health Organization criteria for NE-SAM were
      included. Seven commonly used equations were used for calculating the BSA. Mean
      BSA from the equations was used as reference for comparison. A new equation SAM
      Mosteller modified was also derived. RESULTS: A total of 471 children were
      included. Of the seven equations, Mosteller had minimum root mean square error
      (RMSE) value of 2.89. The goodness of SAM Mosteller modified equation was
      subsequently compared with Mosteller and Boyd in 66 NE-SAM children. The SAM
      Mosteller modified showed least RMSE (2.65), whereas Boyd had maximum.
      CONCLUSIONS: Among seven equations, Mosteller is useful for BSA calculation in NE
      SAM. SAM Mosteller modified equation (164.551 * [Ht * Wt](0.5)) has least error
      and can serve as best measure of BSA in SAM children.

PMID- 23868576
TI  - Neonatal bloodstream infections in a pediatric hospital in Vietnam: a cohort
      study.
AB  - Septicemia and bloodstream infections (BSIs) are major causes of neonatal
      morbidity and mortality in developing countries. We prospectively recorded all
      positive blood cultures (BSI) among neonates admitted consecutively to a tertiary
      pediatric hospital in Vietnam during a 12-month period. Among 5763 neonates, 2202
      blood cultures were performed, of which 399 were positive in 385 neonates. Among
      these, 64 died, 62 in relation to septicemia. Of the BSI isolates, 56% was known
      pathogenic and 48% was gram-negative bacteria, most frequently Klebsiella spp. (n
      = 78), Acinetobacter spp. (n = 58) and Escherichia coli (n = 21). Only three
      Streptococcus spp. were identified, none group B. Resistance against antibiotics
      applied was common. The mortality was highest in neonates with gram-negative BSI
      compared with no confirmed BSI and gram-positive BSI (P < 0.01). In this setting,
      the majority of BSI were likely to have been transmitted from the environment.
      Improvement of hygienic precautions and systematic BSI surveillance are
      recommended. 

PMID- 23868578
TI  - A General Approach To Fabricate Fe3O4 Nanoparticles Decorated with Pd, Au, and
      Rh: Magnetically Recoverable and Reusable Catalysts for Suzuki C-C Cross-Coupling
      Reactions, Hydrogenation, and Sequential Reactions.
AB  - A facile strategy has been explored for loading noble metals onto the surface of
      ferrite nanoparticles with the assistance of phosphine-functionalized linkers.
      Palladium loading is shown to occur with participation of both the phosphine
      function and the surface hydroxyl groups. Hybrid nanoparticles containing
      simultaneously Pd and Au (or Rh) are obtained by successive loading of metals.
      Similarly, ferrite nanoparticles decorated with Pd, Au, and Rh have also been
      formed by using the same strategy. The catalytic properties of the new
      nanoparticles are evidenced in processes such as reduction of 4-nitrophenol or
      hydrogenation of styrene. Besides, the sequential process involving a cross
      coupling reaction followed by reduction of 1-nitrobiphenyl has been successfully
      achieved by employing Pd/Au decorated nanoferrite particles. 

PMID- 23868579
TI  - Reconstructing integrin activation in vitro.
AB  - Integrin activation leads to an increased affinity for the extracellular matrix
      and regulates many cellular processes such as cell adhesion and migration. To
      capture the process of integrin inside-out activation in a purified system, we
      describe here methods to isolate platelet alphaIIbbeta3 integrins in the inactive
      state and to incorporate them into phospholipid nanodiscs each bearing a single
      lipid-embedded alphaIIbbeta3 integrin. We delineate a simple enzyme-linked
      immunosorbent assay that can be used in conjunction with binding of an activation
      specific monoclonal antibody, PAC1, to monitor the affinity of the integrin
      before and after the addition of activators such as the Talin Head Domain (THD).
      The system has been used to show that binding of the THD to both the integrin and
      the phospholipid bilayer is necessary and sufficient to activate and promote
      molecular extension of unclustered integrins in the absence of force. This method
      can be used to test various integrin-binding proteins, membrane phospholipid
      compositions and different types of integrins. It can also serve as the nidus for
      synthetic assembly of adhesion plaque like complexes from purified proteins. 

PMID- 23868580
TI  - Quantifying cellular adhesion to covalently immobilized extracellular matrix
      proteins by single-cell force spectroscopy.
AB  - Atomic force microscopy (AFM)-based single-cell force spectroscopy (SCFS) enables
      the quantitative study of cell adhesion under physiological conditions. SCFS
      probes adhesive interactions of single living cells with substrates such as
      extracellular matrix (ECM) proteins and other cells. Here, we present a protocol
      to quantitatively study the adhesion of HeLa cells to covalently immobilized
      fibronectin and MatrigelTM using SCFS. We describe procedures for (a)
      functionalization of AFM cantilevers, (b) preparation of maleic anhydride
      copolymer thin films, (c) covalent immobilization of ECM proteins on the thin
      films, (d) cell handling and attachment to the AFM cantilever, and (e)
      measurement of adhesion forces. The protocol can be easily modified for other
      cell types and substrate proteins. 

PMID- 23868581
TI  - A multimode-TIRFM and microfluidic technique to examine platelet adhesion
      dynamics.
AB  - Fluorescence microscopy techniques have provided important insights into the
      structural and signalling events occurring during platelet adhesion under both
      static and blood flow conditions. However, due to limitations in sectioning
      ability and sensitivity these techniques are restricted in their capacity to
      precisely image the adhesion footprint of spreading platelets. In particular,
      investigation of platelet adhesion under hemodynamic shear stress requires an
      imaging platform with high spatial discrimination and sensitivity and rapid
      temporal resolution. This chapter describes in detail a multimode imaging
      approach combining total internal reflection fluorescence microscopy (TIRFM) with
      high speed epifluorescence and differential interference contrast (DIC)
      microscopy along with a novel microfluidic perfusion system developed in our
      laboratory to examine platelet membrane adhesion dynamics under static and flow
      conditions. 

PMID- 23868582
TI  - Localization-based super-resolution imaging of cellular structures.
AB  - Fluorescence microscopy allows direct visualization of fluorescently tagged
      proteins within cells. However, the spatial resolution of conventional
      fluorescence microscopes is limited by diffraction to ~250 nm, prompting the
      development of super-resolution microscopy which offers resolution approaching
      the scale of single proteins, i.e., ~20 nm. Here, we describe protocols for
      single molecule localization-based super-resolution imaging, using focal adhesion
      proteins as an example and employing either photoswitchable fluorophores or
      photoactivatable fluorescent proteins. These protocols should also be easily
      adaptable to imaging a broad array of macromolecular assemblies in cells whose
      components can be fluorescently tagged and assemble into high density structures.

PMID- 23868583
TI  - Use of microarray analysis to investigate EMT gene signatures.
AB  - The epithelial-to-mesenchymal transition (EMT) is a widely studied program of
      development of cells characterized by loss of cell adhesion, repression of E
      cadherin expression, and increased cell mobility. Microarrays have become a well
      established technique for simultaneously measuring the expression of thousands of
      transcripts encoded by the genome. In this chapter, we demonstrate how microarray
      analysis can be used to assess the role of EMT-genes associated with a collagen
      invading phenotype by generating a gene expression signature and relating this to
      cell line and tumor datasets from published microarray studies. 

PMID- 23868584
TI  - Podosome reformation in macrophages: assays and analysis.
AB  - Podosomes are multifunctional organelles of invasive cells that combine several
      key abilities including cell-matrix adhesion, extracellular matrix degradation,
      and mechanosensing. In combination with their high turnover rates that allow
      quick adaptation to the pericellular environment, podosomes are likely to play
      important roles during invasive migration of cells. Primary human macrophages
      constitutively form numerous podosomes and are thus an ideal system for the
      quantitative study of podosome dynamics. This protocol describes assays for the
      study of podosome dynamics, namely, reformation of podosomes, in fixed and living
      cells, with subsequent software-based analyses allowing the extraction of
      quantitative parameters such as the number of podosomes per cell, podosome
      density, and half times for podosome disruption and reformation. Moreover, we
      describe the preparation of podosome-enriched cell fractions and their analysis
      by immunoblotting. 

PMID- 23868585
TI  - Mobile and three-dimensional presentation of adhesion proteins within microwells.
AB  - On traditional cell culture substrates cells adhere to a planar 2D surface where
      ligands are presented immobile. A more realistic presentation of cell adhesion
      ligands which can account for lateral mobility and a more tissue-like 3D
      presentation would allow studies addressing fundamental questions of significant
      importance for applications such as tissue engineering and implant intregration.
      To study the effect of lateral mobility of cell membrane interaction cues in
      three dimensions, we have developed and characterized a platform which
      generically enables patterning of single cells into microwells presenting a cell
      membrane mimetic interface pre-patterned to its walls. Here, we describe its
      application in presenting a soluble cell adhesive ligand coupled through
      streptavidin-antibody linkage to lipids in a supported lipid bilayer (SLB) coated
      microwell. The lateral mobility of the presented ligands was controlled through a
      small change in temperature. The SLB phospholipid composition was choosen such
      that below its melting transition at 30  degrees C the ligands are immobile,
      while above 30  degrees C they are laterally mobile. The platform thus enables
      the investigation of cell adhesion to either laterally immobile or mobile E
      cadherin ligand presented on the same cell membrane mimetic surface. 

PMID- 23868586
TI  - Basement membrane invasion assays: native basement membrane and chemoinvasion
      assay.
AB  - To escape the primary tumor and infiltrate stromal compartments, invasive cancer
      cells must traverse the basement membrane (BM). To break this dense matrix, cells
      develop finger-like protrusions, called invadopodia, at their ventral surface.
      Invadopodia secrete proteases to degrade the BM, and then elongate which allows
      the cell to invade the subjacent tissue. Here, we describe two complementary
      invasion assays. The native BM invasion assay, based on BM isolated from rat or
      mouse mesentery, is a physiologically significant approach for studying the
      stages of BM crossing at the cellular level. The Matrigel-based chemoinvasion
      assay is a powerful technique for studying invadopodia's molecular composition
      and organization at the subcellular level. 

PMID- 23868587
TI  - Cytoplasmic actin: purification and single molecule assembly assays.
AB  - The actin cytoskeleton is essential to all eukaryotic cells. In addition to
      playing important structural roles, assembly of actin into filaments powers
      diverse cellular processes, including cell motility, cytokinesis, and
      endocytosis. Actin polymerization is tightly regulated by its numerous cofactors,
      which control spatial and temporal assembly of actin as well as the physical
      properties of these filaments. Development of an in vitro model of actin
      polymerization from purified components has allowed for great advances in
      determining the effects of these proteins on the actin cytoskeleton. Here we
      describe how to use the pyrene actin assembly assay to determine the effect of a
      protein on the kinetics of actin assembly, either directly or as mediated by
      proteins such as nucleation or capping factors. Secondly, we show how
      fluorescently labeled phalloidin can be used to visualize the filaments that are
      created in vitro to give insight into how proteins regulate actin filament
      structure. Finally, we describe a method for visualizing dynamic assembly and
      disassembly of single actin filaments and fluorescently labeled actin binding
      proteins using total internal reflection fluorescence (TIRF) microscopy. 

PMID- 23868588
TI  - Synthetic and tissue-derived models for studying rigidity effects on invadopodia
      activity.
AB  - Invasion by cancer cells through the extracellular matrix (ECM) of tissues is a
      critical step in cancer progression and metastasis. Actin-rich subcellular
      protrusions known as invadopodia are thought to facilitate this process by
      localizing proteinases which degrade the ECM and allow for cancer cell
      penetration. We have shown in vitro that invadopodia activity is regulated by the
      rigidity of the ECM, which suggests that matrix remodeling in vivo may also be
      regulated by the mechanical properties of tissues. In order to study rigidity
      effects on invadopodia activity in a controlled manner, we have developed assays
      in which we have conjugated degradable fluorescent matrix molecules to tunable
      synthetic substrates. In addition, we have also utilized ex vivo tissue-derived
      substrates to corroborate our findings. In this chapter, we present detailed
      protocols describing the synthesis and preparation of our synthetic substrates,
      polyacrylamide gels and polyurethane elastomers, for use in these matrix
      degradation assays as well as the steps required to utilize our tissue-derived
      substrates. 

PMID- 23868589
TI  - Determining Rho GTPase activity by an affinity-precipitation assay.
AB  - The Rho GTPases are members of the Ras superfamily of GTPases that are pivotal
      regulators of the actin cytoskeleton. They also contribute to other cellular
      processes such as gene transcription, cell polarity, microtubule dynamics, cell
      cycle progression and vesicle trafficking. Most Rho GTPases act as molecular
      switches cycling between an "active" GTP-bound form and an "inactive" GDP-bound
      form. Hence, to elucidate the mechanisms by which Rho GTPases regulate cellular
      responses, an important parameter to determine is the GTP-loading of each Rho
      family member in cells under different conditions. Here we describe a biochemical
      technique to assess this based on affinity-precipitation of the GTP-bound form
      from whole cell lysates. 

PMID- 23868590
TI  - Proteomic and biochemical methods to study the cytoskeletome.
AB  - The cytoskeleton is fundamental to many cellular functions including cell
      proliferation, differentiation, adhesion, and migration. It is composed of actin,
      microtubules, intermediate filaments, and integrin cell surface receptors, which
      form focal adhesions with the extracellular matrix. These elements are highly
      integrated in the cell providing a rigid network of interconnected cables and
      protein scaffolds, which generate force and mechanical support to maintain cell
      shape and movement. However, the cytoskeleton is not just a simple compilation of
      static filaments that dictate cell adhesion and morphology-it is highly plastic
      with the inherent ability to assemble and disassemble in response to diverse and
      complex cellular cues. Thus, biochemical and proteomic methods are needed to
      better understand the cytoskeleton network and its dynamic signal transduction
      functions in health and disease. This chapter describes methods for the
      biochemical enrichment and mass spectrometry-based proteomic analyses of the
      cytoskeletome. We also detail how these methods can be used to investigate the
      cytoskeletome of migrating cells and their purified pseudopodia membrane
      projections. 

PMID- 23868591
TI  - Fabricating surfaces with distinct geometries and different combinations of cell
      adhesion proteins.
AB  - A step-by-step procedure is described for functionalizing the surface of a glass
      coverslip so that a single cell contacts distinct patterns of extracellular
      matrix and cell-cell adhesion proteins. This dual-micropatterned substratum is
      accomplished through a two-step process. First, extracellular matrix (ECM) is
      microcontact-printed onto a silanized glass surface using electron beam
      lithography, etched resist-coated wafers, and Polydimethylsiloxane (PDMS) stamps
      of differing geometries. Then, non-ECM-coated surfaces are incubated sequentially
      with biotin, NeutrAvidin, and biotinylated Protein A to attach Fc-cadherin fusion
      proteins, Fc, or PEG. Cells are seeded at low density onto the functionalized
      surface for single-cell analysis of protein recruitment/turnover and cellular
      motility. 

PMID- 23868592
TI  - Purification of native Arp2/3 complex from bovine thymus.
AB  - The Arp2/3 complex is an actin filament nucleator involved in cell motility and
      vesicle trafficking. Owing to the role the complex plays in important and
      fundamental cell biological processes, the purified complex is used in
      biochemical assays, reconstituted motility assays, and structural biology. As
      this is a eukaryotic complex assembled from seven polypeptides, the complex is
      purified from eukaryotic sources. Described here is a detailed method for
      purification of the complex from a mammalian tissue, bovine thymus. 

PMID- 23868593
TI  - Purification of Arp2/3 complex from Saccharomyces cerevisiae.
AB  - Much of the cellular control over actin dynamics comes through regulation of
      actin filament initiation. At the molecular level, this is accomplished through a
      collection of cellular protein machines, called actin nucleation factors, which
      position actin monomers to initiate a new actin filament. The Arp2/3 complex is a
      principal actin nucleation factor used throughout the eukaryotic family tree. The
      budding yeast Saccharomyces cerevisiae has proven to be not only an excellent
      genetic platform for the study of the Arp2/3 complex, but also an excellent
      source for the purification of endogenous Arp2/3 complex. Here we describe a
      protocol for the preparation of endogenous Arp2/3 complex from wild type
      Saccharomyces cerevisiae. This protocol produces material suitable for
      biochemical study and yields milligram quantities of purified Arp2/3 complex. 

PMID- 23868594
TI  - Measurement and analysis of in vitro actin polymerization.
AB  - The polymerization of actin underlies force generation in numerous cellular
      processes. While actin polymerization can occur spontaneously, cells maintain
      control over this important process by preventing actin filament nucleation and
      then allowing stimulated polymerization and elongation by several regulated
      factors. Actin polymerization, regulated nucleation, and controlled elongation
      activities can be reconstituted in vitro, and used to probe the signaling
      cascades cells use to control when and where actin polymerization occurs.
      Introducing a pyrene fluorophore allows detection of filament formation by an
      increase in pyrene fluorescence. This method has been used for many years and
      continues to be broadly used, owing to its simplicity and flexibility. Here we
      describe how to perform and analyze these in vitro actin polymerization assays,
      with an emphasis on extracting useful descriptive parameters from kinetic data. 

PMID- 23868595
TI  - Use of the xCELLigence system for real-time analysis of changes in cellular
      motility and adhesion in physiological conditions.
AB  - Investigation of the mechanisms behind the regulation of cellular motility and
      adhesion is key to understanding metastasis and the biology of tumor spreading.
      There are many technologies available for these studies, but the majority of them
      are either dependent on the use of labels or limited to endpoint analysis. The
      xCELLigence RTCA (real-time cell analysis) provides a platform for label free and
      operator independent investigation of the migration, invasion and adhesion
      proprieties of cells in physiologically relevant conditions. The real-time
      kinetic data acquisition also allows for a more accurate characterization of
      short-lived cellular events. In this chapter we describe the use of the
      xCELLigence Real-Time Cell Analyzer to investigate changes in cellular adhesion
      and motility in real time. 

PMID- 23868596
TI  - Measuring chemotaxis using direct visualization microscope chambers.
AB  - Direct visualization chambers are considered the gold standard for measuring and
      analyzing chemotactic responses, because they allow detailed analysis of cellular
      behavior during the process of chemotaxis. We have previously described the
      Insall chamber, an improved chamber for measuring cancer cell chemotaxis. Here,
      we describe in detail how this system can be used to perform two key assays for
      both fast- and slow-moving mammalian and nonmammalian cell types. This allows for
      the detailed analysis of chemotactic responses in linear gradients at the levels
      of both overall cell behavior and subcellular dynamics. 

PMID- 23868597
TI  - In vitro microtubule severing assays.
AB  - Microtubules are rigid and highly dynamic cellular polymers essential for
      intracellular transport, cell division and differentiation. Their stability is
      tightly regulated by a vast array of cellular factors. In vitro microtubule
      assays have proven to be powerful tools for deciphering the mechanism of
      microtubule dynamics regulators such as molecular motors and microtubule
      associated proteins. In this chapter we focus on microtubule severing enzymes
      that use the energy of ATP hydrolysis to introduce internal breaks in the
      microtubule lattice. We present a detailed protocol for a light microscopy based
      in vitro microtubule severing assay that was instrumental in the identification
      and characterization of these enzymes. 

PMID- 23868598
TI  - VE-cadherin status as an indicator of microvascular permeability.
AB  - VE-cadherin phosphorylation and binding partner status are important indicators
      of endothelial permeability. Here we describe several techniques aimed at
      discerning total tyrosine phosphorylation levels of VE-cadherin, VE-cadherin
      phosphorylation on specific tyrosine residues, and the ability of VE-cadherin to
      bind its binding partner beta-catenin. Taken together, these approaches to
      studying VE-cadherin status on microvascular endothelial cells are excellent
      complements to traditional permeability assays. 

PMID- 23868599
TI  - High-resolution live-cell imaging and time-lapse microscopy of invadopodium
      dynamics and tracking analysis.
AB  - Invadopodia are specialized structures of cancer cells which aid in cancer cell
      invasion and metastasis. Therefore, studying the early steps of invadopodium
      assembly and its life cycle at the subcellular level by using high spatiotemporal
      resolution imaging provides an opportunity for understanding the signaling
      mechanisms involved in this very important process. In this chapter, we describe
      the design of a custom-built high-resolution fluorescence microscope which makes
      this challenging imaging possible. We also describe an ImageJ plugin that we have
      developed for tracking of invadopodia and lifetime analysis. 

PMID- 23868601
TI  - Electrospun nanofiber scaffolds for investigating cell-matrix adhesion.
AB  - It has become increasingly clear that the cellular microenvironment, in
      particular the extracellular matrix, plays an important role in regulating cell
      function. However, the extracellular matrix is extraordinarily complex in both
      its makeup and its physical properties. Therefore, there is a need to develop
      model systems to independently evaluate the effect of specific extracellular
      matrix features upon cells. Here we describe a model system to evaluate one
      aspect of the extracellular matrix, its fibrous topology. We describe how to
      generate bio-mimetic nanofibers by electrospinning, how to grow cells on these
      fibers, and also some methods for fixing and visualizing cells grown on these
      fibers. These methods can be used to investigate a wide range of biological
      questions, including, but not limited to, cell-extracellular matrix adhesion and
      cell motility on extracellular matrix. 

PMID- 23868600
TI  - Live cell imaging of RhoGTPase biosensors in tumor cells.
AB  - Tumor cell motility and invasion rely on actin cytoskeleton rearrangements
      mediated by the activation of RhoGTPase signaling pathways. Invadopodia are
      membrane-degrading protrusions that mediate extracellular matrix degradation.
      Here, we provide procedures for imaging RhoGTPase biosensors in tumor cells
      during the formation of invadopodia and matrix degradation. 

PMID- 23868602
TI  - Method for measuring single-molecule adhesion forces and attachment lifetimes of
      protein-membrane interactions.
AB  - Many proteins that reside in the cytoplasm bind directly to cell membranes and
      play roles in signaling, adhesion, metabolism, cell structure, and cell motility.
      Several of these membrane-binding proteins, especially cytoskeletal proteins,
      have mechanical functions that result in the transmission of forces to the plasma
      membrane and organelle-membranes. Despite the importance of these interactions,
      remarkably little is known about the mechanical properties of the bonds between
      membranes and proteins. In this chapter, we describe a single-molecule, optical
      trapping method for the measurement of protein-membrane adhesion forces and force
      dependent attachment-lifetimes. 

PMID- 23868603
TI  - Salivary cytokines in healthy adolescent girls: Intercorrelations, stability, and
      associations with serum cytokines, age, and pubertal stage.
AB  - Theoretically, the measurement of cytokines in saliva may have utility for
      studies of brain, behavior, and immunity in youth. Cytokines in saliva and serum
      were analyzed across three annual assessments in healthy adolescent girls (N =
      114, 11-17 years at enrollment). Samples were assayed for GM-CSF, IFNgamma, IL
      1beta, IL-2, IL-6, IL-8, IL-10, IL-12p70, TNFalpha, adiponectin, and cotinine.
      Results revealed: (1) cytokine levels, except IFNgamma and IL-10, were detectable
      in saliva, and salivary levels, except IL-8 and IL-1beta, were lower than serum
      levels; (2) salivary cytokine levels were lower in older girls and positively
      associated with adiponectin; (3) compared to serum levels, the correlations
      between salivary cytokines were higher, but salivary cytokines were less stable
      across years; and (4) except for IL-1beta, there were no significant serum-saliva
      associations. Variation in basal salivary cytokine levels in healthy adolescent
      girls reflect compartmentalized activity of the oral mucosal immune system,
      rather than systemic cytokine activity.

PMID- 23868604
TI  - Does overgrowth of costal cartilage cause pectus carinatum? A three-dimensional
      computed tomography evaluation of rib length and costal cartilage length in
      patients with asymmetric pectus carinatum.
AB  - OBJECTIVES: To evaluate whether the overgrowth of costal cartilage may cause
      pectus carinatum using three-dimensional (3D) computed tomography (CT). METHODS:
      Twenty-two patients with asymmetric pectus carinatum were included. The fourth,
      fifth and sixth ribs and costal cartilages were semi-automatically traced, and
      their full lengths were measured on three-dimensional CT images using curved
      multi-planar reformatted (MPR) techniques. The rib length and costal cartilage
      length, the total combined length of the rib and costal cartilage and the ratio
      of the cartilage and rib lengths (C/R ratio) in each patient were compared
      between the protruding side and the opposite side at the levels of the fourth,
      fifth and sixth ribs. RESULTS: The length of the costal cartilage was not
      different between the more protruded side and the contralateral side (55.8 +/-
      9.8 mm vs 55.9 +/- 9.3 mm at the fourth, 70 +/- 10.8 mm vs 71.6 +/- 10.8 mm at
      the fifth and 97.8 +/- 13.2 mm vs 99.8 +/- 15.5 mm at the sixth; P > 0.05). There
      were also no significant differences between the lengths of ribs. (265.8 +/- 34.9
      mm vs 266.3 +/- 32.9 mm at the fourth, 279.7 +/- 32.7 mm vs 280.6 +/- 32.4 mm at
      the fifth and 283.8 +/- 33.9 mm vs 283.9 +/- 32.3 mm at the sixth; P > 0.05).
      There was no statistically significant difference in either the total length of
      rib and costal cartilage or the C/R ratio according to side of the chest (P >
      0.05). CONCLUSIONS: In patients with asymmetric pectus carinatum, the lengths of
      the fourth, fifth and sixth costal cartilage on the more protruded side were not
      different from those on the contralateral side. These findings suggest that
      overgrowth of costal cartilage cannot explain the asymmetric protrusion of
      anterior chest wall and may not be the main cause of pectus carinatum.

PMID- 23868605
TI  - The endovascular occlusion system for safe and immediate peripheral vessel
      occlusion during vascular interventions.
AB  - Endovascular occlusion of blood vessels is an important part of interventional
      therapy concepts. Here, we evaluate the feasibility, procedural safety and
      efficacy of the novel endovascular occlusion system (EOS) in the arterial system
      in a porcine model. Thirteen devices were deployed in the iliac and femoral
      arteries (diameter: 4-5 mm) of five adult swine. Post-deployment angiography was
      performed at 1, 5 and 10 min and 6 h. All devices (n = 13) could be successfully
      delivered without any complications, such as dissection, perforation or rupture.
      The devices could be easily advanced to the target vessel segment, deployed at
      the intended target location and produced immediate and complete vessel occlusion
      which was confirmed to be maintained after 6 h. No leaks, recanalization or
      device migration was observed. In this pilot study, we demonstrate the
      feasibility, safety and efficacy of immediate vessel occlusion with the EOS
      device in the peripheral arterial system in a porcine animal model. Our data
      indicate that this novel device allows precise delivery without the occurrence of
      cardiovascular complications. Owing to its long-term safety and efficacy the EOS
      may represent a promising and effective alternative to currently available
      devices for vessel occlusion during vascular interventions. 

PMID- 23868606
TI  - Partial cardiac autotransplantation with a concomitant mitral valve, aortic valve
      replacement and tricuspid plasty.
AB  - We describe a case with left atrial volume reduction of a giant left atrium,
      treated successfully by partial cardiac autotransplantation, concomitant mitral
      and aortic valve replacement, and tricuspid valve plasty. We obtained good
      results at the 1-year follow-up. 

PMID- 23868608
TI  - Person-centric clinical trials: an opportunity for the good clinical practice
      (GCP)-practice-based research network.
AB  - Practice-based research networks (PBRNs) can function as a platform for delivery
      of patient-centered care consistent with the Patient Protection and Affordable
      Care Act. Patient-centered (centric) clinical studies encourage the patient to be
      an integral part of study design and outcome. The patient's electronic health
      record contributes to the shared national health care data set. PBRNs integrate
      health care data in real time at the point of care and reflect the full context
      of the person's health. PBRNs designed under the principles of good clinical
      practice (GCP) validate studies related to comparative effectiveness research and
      drug development. PBRNs can generate large amounts of data from known patient
      histories so that side effects can be assessed in their totality. The larger and
      more diverse number of patients recruited suggests that point-of-care-data, where
      both provider and patient participate in the treatment, may be more robust in
      that side effects, drug-drug interactions and number of concomitant medications
      used may be identified earlier in the development process. The GCP PBRN concept
      affords continuous patient information for both care and research purposes. These
      all contribute to an ethical approach for the pharmaceutical industry to generate
      clinical research data for regulatory submission and to contribute to a HIPAA
      compliant national database that could contribute to improved health care
      delivery and pharmacovigilance. 

PMID- 23868607
TI  - H2O2-responsive molecularly engineered polymer nanoparticles as
      ischemia/reperfusion-targeted nanotherapeutic agents.
AB  - The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the
      overproduction of reactive oxygen species (ROS). Hydrogen peroxide (H2O2), the
      most abundant form of ROS produced during I/R, causes inflammation, apoptosis and
      subsequent tissue damages. Here, we report H2O2-responsive antioxidant
      nanoparticles formulated from copolyoxalate containing vanillyl alcohol (VA)
      (PVAX) as a novel I/R-targeted nanotherapeutic agent. PVAX was designed to
      incorporate VA and H2O2-responsive peroxalate ester linkages covalently in its
      backbone. PVAX nanoparticles therefore degrade and release VA, which is able to
      reduce the generation of ROS, and exert anti-inflammatory and anti-apoptotic
      activity. In hind-limb I/R and liver I/R models in mice, PVAX nanoparticles
      specifically reacted with overproduced H2O2 and exerted highly potent anti
      inflammatory and anti-apoptotic activities that reduced cellular damages.
      Therefore, PVAX nanoparticles have tremendous potential as nanotherapeutic agents
      for I/R injury and H2O2-associated diseases. 

PMID- 23868609
TI  - Advanced nuclear analytical and related techniques for the growing challenges in
      nanotoxicology.
AB  - Manufactured nanomaterials with novel physicochemical properties are an important
      basis for nanosciences and related technologies. Nanotoxicology, aiming to
      understand the principles of interactions at the nano-bio interface and the
      relationship between the physicochemical properties of nanomaterials and their
      toxicological profiles, has become a new frontier in nanoscience. Nearly one
      decade of nanotoxicology research has shown that the interactions between
      nanomaterials and proteins, cells, animals, humans and the environment as well as
      the underlying mechanisms of toxicity for nanomaterials are remarkably
      complicated, requiring dedicated analytical methodology and tools. Because of
      their advantages of absolute quantification, high sensitivity, excellent accuracy
      and precision, low matrix effects and non-destructiveness, nuclear analytical
      techniques have been playing important roles in the study of nanotoxicology. A
      systematic summary and comprehensive review of the advanced nuclear analytical
      and related techniques in nanotoxicology is greatly needed. In this review
      article, we present a comprehensive overview of nuclear analytical techniques
      applied to the physicochemical characterization of nanomaterials, structural
      analysis of bio-nano interactions, visualization of nanomaterials in vitro,
      quantification of bio-distribution, bio-accumulation, and transformation of
      nanomaterials in vivo. As important complementary tools, optical imaging
      technologies are also highlighted. Future directions regarding advanced nuclear
      analytical approaches for nanotoxicology are also discussed. The rapid
      development of advanced light source-based techniques will enable new high
      throughput screening techniques and provide high sensitivity with low detection
      limits, which are required for the distribution, imaging, and structural analysis
      of nanomaterials, and the molecular information of biomarkers for all aspects of
      nanotoxicology. 

PMID- 23868610
TI  - Synthesis of aminocyclobutanes by iron-catalyzed [2+2] cycloaddition.

PMID- 23868611
TI  - Characteristics and outcome of pediatric non-Hodgkin lymphoma patients with
      ovarian infiltration at presentation.
AB  - BACKGROUND: Ovarian infiltration in pediatric non-Hodgkin lymphoma (NHL) at
      presentation is rare and information on outcome is scarce and mainly based on
      case reports and small series. PROCEDURE: Evaluation of clinical characteristics
      and outcome of ovarian infiltrated pediatric NHL cases of a single center, and an
      extensive review of the all cases reported so far in literature. RESULTS: At
      presentation, 6/60 female NHL cases of our center had ovarian infiltration, and
      combining these cases with earlier case reports, a total of 42 cases were
      identified. Median age at presentation was 10.9 years (range 0-18), and all but
      one had a B-cell immunophenotype, with 32/42 cases being classified as Burkitt.
      Bilateral involvement was reported in 26/41 cases, of which 22 were bilaterally
      ovariectomized as first treatment. All cases were treated with chemotherapy.
      Relapses were reported in 9/36 and death in 16/36. After follow-up in our center
      (median 13.4 years), in 2 cases anti-Mullerian hormone (AMH) values were
      available (2.1 and 0.9 ug/L), in non-ovarian cases median 2.2 ug/L. CONCLUSIONS:
      We conclude that in case of ovarian tumors with negative markers, NHL should be
      considered in order to avoid unnecessary surgery.

PMID- 23868612
TI  - Use of a benzimidazole derivative BF-188 in fluorescence multispectral imaging
      for selective visualization of tau protein fibrils in the Alzheimer's disease
      brain.
AB  - PURPOSE: Selective visualization of amyloid-beta and tau protein deposits will
      help to understand the pathophysiology of Alzheimer's disease (AD). Here, we
      introduce a novel fluorescent probe that can distinguish between these two
      deposits by multispectral fluorescence imaging technique. PROCEDURES:
      Fluorescence spectral analysis was performed using AD brain sections stained with
      novel fluorescence compounds. Competitive binding assay using [(3)H]-PiB was
      performed to evaluate the binding affinity of BF-188 for synthetic amyloid-beta
      (Abeta) and tau fibrils. RESULTS: In AD brain sections, BF-188 clearly stained
      Abeta and tau protein deposits with different fluorescence spectra. In vitro
      binding assays indicated that BF-188 bound to both amyloid-beta and tau fibrils
      with high affinity (K i  < 10 nM). In addition, BF-188 showed an excellent blood
      brain barrier permeability in mice. CONCLUSION: Multispectral imaging with BF-188
      could potentially be used for selective in vivo imaging of tau deposits as well
      as amyloid-beta in the brain.

PMID- 23868613
TI  - Competitive testing of health behavior theories: how do benefits, barriers,
      subjective norm, and intention influence mammography behavior?
AB  - BACKGROUND: Competitive hypothesis testing may explain differences in predictive
      power across multiple health behavior theories. PURPOSE: We tested competing
      hypotheses of the Health Belief Model (HBM) and Theory of Reasoned Action (TRA)
      to quantify pathways linking subjective norm, benefits, barriers, intention, and
      mammography behavior. METHODS: We analyzed longitudinal surveys of women veterans
      randomized to the control group of a mammography intervention trial (n = 704). We
      compared direct, partial mediation, and full mediation models with Satorra
      Bentler chi (2) difference testing. RESULTS: Barriers had a direct and indirect
      negative effect on mammography behavior; intention only partially mediated
      barriers. Benefits had little to no effect on behavior and intention; however, it
      was negatively correlated with barriers. Subjective norm directly affected
      behavior and indirectly affected intention through barriers. CONCLUSIONS: Our
      results provide empiric support for different assertions of HBM and TRA. Future
      interventions should test whether building subjective norm and reducing negative
      attitudes increases regular mammography.

PMID- 23868614
TI  - Synthesis and in vitro evaluation of West Nile virus protease inhibitors based on
      the 1,3,4,5-tetrasubstituted 1H-pyrrol-2(5H)-one scaffold.
AB  - West Nile virus (WNV), a member of the Flaviviridae family, is a mosquito-borne
      pathogen that causes a large number of human infections each year. There are
      currently no vaccines or antiviral therapies available for human use against WNV.
      Therefore, efforts to develop new chemotherapeutics against this virus are highly
      desired. In this study, a WNV NS2B-NS3 protease inhibitor with a 1,3,4,5
      tetrasubstituted 1H-pyrrol-2(5H)-one scaffold was identified by screening a small
      library of nonpeptidic compounds. Optimization of this initial hit by the
      synthesis and screening of a focused library of compounds with this scaffold led
      to the identification of a novel uncompetitive inhibitor ((-)-1a16, IC50 =2.2+/
      0.7 MUM) of the WNV NS2B-NS3 protease. Molecular docking of the chiral compound
      onto the WNV protease indicates that the R enantiomer of 1a16 interferes with the
      productive interactions between the NS2B cofactor and the NS3 protease domain and
      is thus the preferred isomer for inhibition of the WNV NS2B-NS3 protease.

PMID- 23868615
TI  - A longitudinal study of normal fetal femur volume.
AB  - OBJECTIVE: Fetal femur volume (FV) is a useful marker of skeletal growth. Our
      objective was to create a normal FV chart in a cohort of healthy pregnant women
      and to assess FV repeatability. METHOD: The method used was a prospective,
      observational study using 3D ultrasound. Low-risk pregnant women underwent serial
      scans from 14 to 42 weeks. Strict inclusion and exclusion criteria were used in
      order to remove pathological conditions. Pregnancies were dated by last menstrual
      period and confirmed by crown-rump length. FV was measured using three linear
      measurements and a volume equation. Data were analyzed using multilevel modeling.
      Repeatability was assessed using within-subject coefficients of variation (CV),
      intraclass correlation coefficients (ICC), and Bland-Altman plots. RESULTS: A
      total of 180 women underwent 868 scans, a median of five scans per participant.
      Median and centile values were presented in the form of curves, regression
      equations, and table of values per completed week. Intra-observer CV and ICC were
      10.5% and 0.977, respectively; interobserver CV and ICC were 16.8% and 0.923.
      CONCLUSION: This normal FV chart can be used as a prescriptive standard in order
      to assess fetal skeletal growth. Measurement repeatability is satisfactory for
      clinical use, but FV has a larger random error than commonly seen with standard
      2D biometry.

PMID- 23868616
TI  - Lateralization, praxis, and communicative gestures: developmental and comparative
      perspectives.

PMID- 23868617
TI  - Electron delocalization explains much of the branching and protobranching
      stability.

PMID- 23868618
TI  - Total thyroidectomy for Graves' disease treatment.
AB  - OBJECTIVES: Graves' disease (GD) is the most common cause of hyperthyroidism, and
      accounts worldwide for 60-80% of all cases. The diagnosis is based on clinical
      findings, and is confirmed by the presence of TRAB, suppression of TSH, and
      elevation of free thyroxin (free T4), and triiodinethyronin (free T3). GD can be
      treated by antithyroid drugs, radioactive iodine, or surgery. The aim of this
      study was to review retrospectively the surgical management, in terms of safety
      and efficacy, in 50 patients operated in the Department of Surgical Sciences
      since 2005 through 2010 and followed up at the Endocrinology Unit A of the
      Experimental Medicine Department. We assessed postoperative complications, which
      included the presence, persistence and development of ophthalmopathy, transient
      hypocalcemia, permanent hypoparathyroidism and recurrent laryngeal nerve palsy.
      MATERIALS AND METHODS: We analyzed data from 50 patients with GD who were
      eligible and underwent Total Thyroidectomy (TT). Thirty-nine patients underwent
      TT for recurrent hyperthyroidism after medical therapy and eleven patients for
      severe ophtalmopathy. The mean follow up was 41 months (range: 10-70). RESULTS:
      Eleven patients had ophtalmopathy before surgery. Four patients developed an
      ophtalmopathy after surgery. Eleven patients presented hypocalcemia, transient in
      ten patients and permanent in one patient. Five patients developed a transient
      disphony. Conclusions. Total thyroidectomy is a safe and radical procedure in
      Graves' disease treatment. Complications of TT are not different than subtotal
      thyroidectomy if it's performed by expert surgeons.

PMID- 23868619
TI  - Anomalous structures of the liver: an anatomical insight.
AB  - BACKGROUND AND AIMS: Anomalous structures of the liver are incidentally detected
      during autopsies or during routine cadaveric dissection. The present study aimed
      to observe the abnormal shapes of quadrate lobe, accessory sulci and ligamentum
      teres of the liver. MATERIALS AND METHODS: A total of 20 formalin fixed cadaveric
      livers (n=20), irrespective of the sex, were taken for this study. These
      specimens belonged to cadavers of unknown origins. The presence of accessory
      sulci and abnormalities related to the quadrate lobe and ligamentum teres were
      studied in detail. Morphometric measurements were taken for the abnormal
      accessory sulci and abnormal quadrate lobes. RESULTS: Variable shapes of the
      quadrate lobes were observed with 8 (40%) being rectangular, 6 (30%) being pear
      shaped, 4 (20%) being triangular and another 2 specimens (10%) which were square
      in shape. The presences of accessory sulci on the diaphragmatic surface of the
      liver were observed in 2 specimens (10%). Ligamentum teres traversed the groove
      in 18 (90%) while in 2 (10%) specimens, the ligamentum teres was embedded in the
      groove and it was covered by parenchymatous tissue of the liver it from the side
      of the quadrate lobe. CONCLUSION: Prior anatomical knowledge of the presence of
      the anomalous structures in the liver with may be helpful for the radiologist and
      surgeons for correct interpretation of radiographs and planning appropriate
      hepatobiliary surgeries.

PMID- 23868620
TI  - The treatment with ursodeoxycholic acid in elderly patients affected by NAFLD and
      metabolic syndrome: a case-control study.
AB  - AIMS: Evaluating the prevalence and the degree of steatosis in geriatric patients
      (65 to 85 years of age) with Metabolic Syndrome (defined by ATP III criteria);
      searching for metabolic factors which are predictive for the degree of steatosis;
      evaluating the efficacy of Ursodeoxycholic Acid (UDCA) for 6 months in the
      treatment of patients with NAFLD or NASH. MATERIALS AND METHODS: We studied 87
      geriatric patients with Metabolic Syndrome. Steatosis was diagnosed and graded by
      laboratory assessment and ultrasonography, method based on the determination of
      liver/kidney ratio through grey-scale intensity, which was calculated as an index
      of the severity of the steatosis: it could oscilates from 0 (none) to 3 (severe).
      We randomized the geriatric patients into two groups: Ursodeoxycholic Acid (UDCA)
      treated group (n=43 pz) and diet-treated group (1200 Kcal/die for female, 1500
      Kcal/die for male) (n=44 pz), for a period of 6 months. BMI, principal symptoms,
      liver function, blood lipids, ultrasonography liver were evaluated respectively
      before and after treatment. RESULTS: The prevalence of steatosis was 100% (26
      mild steatosis cases, 38 moderate cases and 23 severe cases) in our patients with
      Metabolic Syndrome. Of the 43 subjects assigned to receive 300-450 mg/d of UDCA
      and diet, the hepatic steatosis index decreased on the average, of the 75%. Serum
      AST, ALT and gamma-GT decreased significantly at 3 months already (p<0.001).
      CONCLUSIONS: UDCA improves liver enzymes and ultrasonography immaging in
      geriatric patients with NAFLD or NASH. Unexpectedly, UDCA has resulted in
      beneficial effects on glycemic control and insulin sensitivity.

PMID- 23868621
TI  - Prolidase activity and oxidative stress parameters in patients with nasal polyps.
AB  - BACKGROUND AND AIM: Oxidative stress is believed to have a role in the
      development of nasal polyps (NPs). It is also known that prolidase activity
      increases secondary to chronic inflammation. The purpose of this study was to
      evaluate the association between prolidase activity and oxidative stress
      parameters in patients with NPs. MATERIALS AND METHODS: Sixty patients with NPs,
      septal deviations and the concha hypertrophies were recruited to the study.
      Patients were divided into two groups; group 1 (n=30) consisted of patients with
      NPs, and group 2 (n=30) included patients with septal deviations and concha
      hypertrophies. Polyp specimens were taken from all patients who underwent
      endoscopic surgery for NPs. Control specimens were acquired from patients who
      underwent an operation for septoplasty or concha hypertrophy. Blood and tissue
      samples were obtained to assess lipid hydroperoxide (LOOH), catalase (CAT) and
      prolidase activity. RESULTS: Compared to group 2, group 1 had significantly
      higher LOOH and prolidase levels, and lower CAT levels both in serum and tissue
      samples (p<0.05 for all). Prolidase activity was correlated with increased LOOH
      and decreased CAT levels (r = 0.507 p = 0.004; r = - 0.579, p = 0.001,
      respectively). CONCLUSIONS: Our study demonstrated that oxidative stress and
      prolidase activity, both in serum and the tissue in patients with NPs, were
      higher than in patients without NPs.

PMID- 23868622
TI  - A study of knowledge and attitudes of registered nurses towards pain management
      in an urban hospital.
AB  - BACKGROUND AND AIMS: Nurses play a pivotal role in pain management. Unrelieved
      pain significantly interferes with patient's quality of life and is of great
      concern to nurses. The aim of this study was to determine the knowledge level and
      attitudes of nurses related to pain management. MATERIALS AND METHODS: This
      descriptive study was conducted in an urban hospital. A total of 84 registered
      nurses were recruited using a modified version of questionnaire of Knowledge and
      Attitudes Survey Regarding Pain. RESULTS: The findings showed that respondents
      possessed good knowledge (99.12+/-14.810) and attitude (66.00 +/-10.415) towards
      pain management. Fifty five respondents (66%) responded as positive to cultural
      beliefs affecting their pain management and 65 respondents (77%) viewed that
      their personal experiences had influenced their practice in pain management.
      Another 45 respondents (54%) reported they have attended pain course. There was
      no significant difference in pain management between respondents' year of
      service, cultural belief and personal experiences (p=>0.05). In terms of
      knowledge towards to pain management, respondents' age groups of more than 40
      years were noted to possess better knowledge (p=0.046), unmarried respondents
      (p=0.018), and attended pain course (p=0.001) were significant. Attitude towards
      to pain management was not significant (p<=0.05). CONCLUSION: Nurses' knowledge
      and attitudes scores were impressive but there is room for further improvement to
      pain management. Continuing education organized by the hospital had significant
      impact on the nurses. However, this education course has to be reinforced from
      time to time in order to improve patients' pain experiences.

PMID- 23868623
TI  - [A case of Takotsubo Syndrome complicated by not embolic cerebral].
AB  - The Takotsubo syndrome is characterized by transient left ventricular dysfunction
      with ST segment elevation in all or some leads, T-wave inversion in anterior and
      inferior leads and elevate cardiac biomarkers (HS troponin), which can mimic an
      acute coronary syndrome (STEMI) in the absence of obstructive coronary disease.
      The echocardiography shows transient alterations in the kinetics of the anterior,
      intermediate and apical segments of the left ventricle which tends to disappear
      within 4-8 weeks. A particular variant of Takotsubo Syndrome is reported in a 73
      year-old man.

PMID- 23868624
TI  - Mismanagement of cat bite wound: lessons to learn.
AB  - Animal inflicted wounds, left untreated may result in chronic bacterial or fungal
      infection. Clinical features of these infections may overlap leading to a delay
      in diagnosis and treatment. We report a case of chronic non-healing cat bite
      wound treated with several antibiotics without improvement. Later patient
      developed the classical "sporotrichoid spread" and a presumptive diagnosis of
      sporotrichosis was made. Laboratory investigation for fungal culture and skin
      biopsy failed to identify the underlying pathogen. A trial of oral antifungal
      agent resulted in complete recovery of the lesions implicating fungus as the
      causative pathogen. Physicians should have a high index of suspicion for fungal
      infections when managing animal inflicted wounds.

PMID- 23868625
TI  - Retroaortic left renal vein associated with unilateral superior renal polar
      artery: a clinico-embryological perspective.
AB  - The aim of the current study is to report an unusual occurrence of a retroaortic
      left renal vein in an adult male cadaver of Caucasian origin. This unusual
      variant was discovered during the course of preclinical educational training
      programme for undergraduate medical students. The vascular anomaly was dissected
      and the surrounding adnexa carefully studied for associated variations.
      Subsequently, morphometry was performed on the specimen to measure certain
      important parameters. The left renal vein was found to emerge from lower part of
      renal hilum and traversed posterior to abdominal aorta and finally terminated
      into Inferior vena cava. Additionally, the left renal artery was higher in
      position and originated from the abdominal aorta at the level of upper border of
      body of Ist lumbar vertebra. This type of anomaly is very important as it may be
      associated with varicocoele. Furthermore, in preoperative planning for
      nephrectomy, partial nephrectomy and living donor nephrectomy, the surgeons
      should keep in mind the possibility of this vascular anomaly. It is also stated
      that left renal vein appears to be at the centre of a huge venous network which
      makes the nephrectomy hazardous and permits the spread of infectious material and
      neoplasms.

PMID- 23868626
TI  - [The possible uses of balneotherapy in treating chronic venous insufficiency of
      lower limbs].
AB  - The Chronic Venous Insufficiency (CVI) of inferior limbs is a widespread disease,
      with an increasing incidence as a consequence of longer life expectance, life
      style, obesity, smoking, use of drugs as oestrogens and progestins and working
      conditions. Medical therapy is still lacking for evidence of efficacy, and
      compression therapy is useful only in preventing a worsening of this condition.
      Surgical treatment is the only radical therapy effective for the advanced phases
      of the disease. In this context spa balneotherapy can be considered as a possible
      chance to improve some subjective and objective symptoms of CVI of inferior
      limbs, and to prevent worsening of this condition. The authors performed a review
      of the relevant scientific literature concerning the treatment of CVI of inferior
      limbs with mineral water balneotherapy, in order to evaluate its effects on
      objective and subjective symptoms and its effectiveness to prevent further
      worsening. We searched the PubMed/Medline, Cochrane Library, Embase, Web of
      Science databases for articles published between 1990 and 2011 on this topic. To
      this end, the authors selected few clinical-controlled and case-controlled
      studies; patients affected from CVI of inferior limbs were treated with
      balneotherapy at health spas with sulphureous, sulphate, salsojodic or
      salsobromojodic mineral waters. Baths in mineral waters were often associated
      with idromassotherapy and vascular pathway. Effects of spa balneotherapy are
      related to some aspecific properties, like hydrostatic pressure, osmotic pressure
      and water temperature, partly related with specific chemico-physical properties
      of the adopted mineral water. The controlled clinical studies on spa therapy
      showed significant improvement of subjective (such as itch, paresthesias, pain,
      heaviness) and objective symptoms (namely edema and skin discromias). These
      studies suggest that spa balneotherapy may give a good chance of secondary
      prevention and effective therapy of CVI of inferior limbs, but also that it needs
      of other clinical controlled trials.

PMID- 23868627
TI  - Effects of a dietary supplement on cholesterol in subjects with moderate
      hypercholesterolemia.
AB  - BACKGROUND AND AIMS: Prospective studies have demonstrated that the risk of death
      due to ischaemic heart disease is strongly correlated with blood cholesterol (TC)
      levels. Diet is the basic treatment for all dyslipidaemia. If diet alone proves
      inadequate, supplements can be used to try to reduce cholesterol levels. These
      substances are indicated in moderate dyslipidaemia, as they are able to induce a
      moderate reduction in blood cholesterol. The objective of our study was to
      investigate the effects of a dietary supplement containing Omega-3, Policosanol,
      Resveratrol, L-carnitine, Monascus purpureus, Coenzyme Q10, Vitamin B6 and
      Vitamin B12 on TC (primary end point) and LDL, triglycerides and HDL (secondary
      endpoints). PATIENTS AND METHODS: The study involved 40 men and 40 women
      recruited from the outpatient section of our Department randomly assigned to the
      treatment group (A) or the control group (B). RESULTS: There was a statistically
      significant reduction in TC 6 months after the end of treatment in both groups.
      In Group A, there was also a statistically significant change in HDL, LDL and TG,
      while in group B, there was no statistically significant change in HDL, LDL or
      TG. CONCLUSIONS: The dietary supplement used in our study, in combination with a
      balanced diet and physical exercise, was found to induce a significant reduction
      in TC and LDL-C and an improvement in HDL-C. In contrast, while a balanced diet
      together with physical exercise but without the dietary supplement produced a
      significant reduction in TC, it had no significant effect on the other lipid
      parameters tested.

PMID- 23868628
TI  - [Efficacy and safety of a salsobromoiodic gel solution in proctological surgery].
AB  - BACKGROUND: Surgical procedures for ano-rectal pathologies are always conditioned
      by an high percentage of side-effects. Indeed, the prevention of probable
      complications such as the non tissue-recovery or infection is a fundamental topic
      to guarantee an adequate follow-up. The aim of this comparative study is to
      assess the short-term outcomes of the use of a solution salsobromoiodic gel
      solution in postoperative period of patients undergoing proctological surgery.
      MATERIALS AND METHODS: The authors selected retrospectively a population of 80
      patients, undergoing surgery for Milligan-Morgan hemorrhoidectomy. Based on the
      recommended medications postoperatively, patients were divided into two groups:
      the Group A applied the salsobromoiodic solution gel on the perianal surgical
      wound in the postoperative period, the Group B did not use any medical facility
      with the exception of a soap at neutral pH. The clinical features assessed at 5,
      10, 15 and 30 days after surgery were: pain, burning and itching lenght, the
      healing time, the presence or absence of early or late superinfection, the time
      of re-epithelization, the need for surgical curettage. The subjective evaluation
      of quality of life was assessed using a Visual Analogue Scale (VAS). RESULTS:
      There was a statistically significant reduction in length of postoperative pain
      in patients of Group A compared to Group B (5.6 vs 10.4 days respectively;
      p<0.005). There was a more rapid wound healing and re-epithelialization in group
      A, 15 and 21,3 days, respectively, as compared to Group B, 22.9 and 31.7 days
      (p<0.005). There were no differences between the two groups in terms of burning,
      itching and early and late bacterial infection. Two patients in Group B required
      a surgical debridement of the wound. Patients who used postoperatively
      salsobromoiodic solution declared a better quality of life. CONCLUSIONS: The use
      of salsobromoiodic gel solution in the postoperative proctological surgery,
      resulted safe and was effective in reducing postoperative pain, in contributing
      wounds healing and improving the quality of life, as subjectively assessed by
      each patient.

PMID- 23868629
TI  - Effectiveness of thymoquinone in the treatment of experimental asthma.
AB  - BACKGROUND: Thymoquinone (TQ), the main active constituent of the volatile oil
      extracted from Nigella sativa's seeds, is used for the treatment of inflammatory
      diseases and exhibits a variety of pharmacological effects. METHODS: Twenty-eight
      BALB/c female mice were divided into four groups: I (sham-operated control
      group), II, III, and IV. All groups except for the sham-operated group were
      sensitized and challenged with ovalbumin. The sham-operated group received
      nebulized saline in challenge period. Mice in groups III and IV were administered
      TQ at a dose of 3 mg/kg and dexamethasone 1 mg/kg, respectively,
      intraperitoneally once a day for the final 5 days of the challenge period.
      Animals were sacrificed 24 h after the last drug administration and the airway
      samples were evaluated histologically by light microscopy. RESULTS: All
      histological parameters in Group III, similar to Group IV, were improved when
      compared to Group II. All variables except numbers of goblet cells were found to
      be significantly better in Group III and Group IV compared to Group II.
      CONCLUSIONS: In our study, we demonstrated that TQ administration alleviates the
      pathological changes of chronic asthma. TQ might be a promising therapy for
      asthma in the.

PMID- 23868630
TI  - An evaluation of neuropeptide Y status in subacute sclerosing panencephalitis
      patients.
AB  - AIM: This study aimed to evaluate the neuropeptide Y values of patients with
      subacute sclerosing panencephalitis. MATERIALS AND METHODS: The study comprised
      38 patients diagnosed with subacute sclerosing panencephalitis at our clinic, who
      were being routinely followed-up, together with a control group of 36. Using the
      Risk and Haddad classification for clinical staging, 16 patients were determined
      as Stage II and 22 patients as Stage III. Neuropeptide Y values were measured by
      Enzyme Immunoassay methods. RESULTS: The neuropeptide Y values of the all
      patients with subacute sclerosing panencephalitis were found to be significantly
      high compared to the control group (p<0.01). The neuropeptide Y values of the
      Stage III group were found to be significantly high compared to the Stage II and
      control groups (p<0.05). The neuropeptide Y values of the Stage II group were not
      determined to be significant compared to the control group (p<=0.05).
      CONCLUSIONS: Neuropeptide Y can be considered a useful parameter to confirm
      diagnosis at advanced stages and to establish differences between stages in
      patients with subacute sclerosing panencephalitis.

PMID- 23868631
TI  - The preoperative and postoperative oxidative status of children with chronic
      adenotonsillar hypertrophy.
AB  - AIM: This study aimed to evaluate the preoperative and postoperative oxidative
      status of children with chronic adenotonsillar hypertrophy. MATERIALS AND
      METHODS: The study comprised 25 patients with indications for tonsillectomy
      and/or adenoidectomy following a diagnosis of chronic adenotonsillar hypertrophy
      and 25 age-gender matched control patients were included to the study. Blood
      samples were taken from the patients preoperatively and at four weeks
      postoperatively. Preoperative and postoperative serum total oxidant (TOS) and
      total antioxidant (TAS) levels were measured and the oxidative stress index (OSI)
      was calculated. RESULTS: The serum total oxidant level and oxidant stress index
      values in the preoperative and postoperative periods of the patients were found
      to be significantly high compared to those of the control group. While the
      preoperative serum total oxidant level values were found to be significantly high
      compared to the postoperative values, no statistical significance was found
      between the total antioxidant and oxidative stress index values. CONCLUSION: The
      development of chronic adenotonsillar hypertrophy plays a role in oxidative
      status and therefore, to neutralize high levels of oxidants in patients, the use
      of antioxidants for a period preoperatively and postoperatively is thought to be
      necessary.

PMID- 23868632
TI  - Hyperglycaemia in patients treated with second generation antipsychotics.
AB  - AIM: The association of second generation antipsychotic medications and
      hyperglycaemia has been reported for Caucasian populations but is unknown for
      asian patients who unfortunately are predisposed to diabetes. We report the
      findings from a health quality improvement project which tracked patients with
      schizophrenia and schizoaffective disorder newly started on second generation
      antipsychotics. MATERIALS AND METHODS: 266 patients were newly started on second
      generation antipsychotics in a 2 year period. Amongst the baseline parameters
      monitored was the fasting plasma glucose levels. Repeat testing was done at 4
      weeks, 12 weeks and 12 months. RESULTS: 14 patients were excluded form the
      analysis as they had diabetes at the start of treatment with second generation
      antipsychotics. Hyperglycaemia was found in 88 patients (34.9%). 68 (77.3%) of
      these patients experienced the Hyperglycaemia at 12 weeks, 3 patients (3.4%) at 4
      weeks and 17 patients (19.3%) at 12 months. Fasting plasma glucose levels were
      highest at 4 weeks. CONCLUSIONS: Despite the limitations of the project, the one
      third prevalence of hyperglycaemia amongst patients newly started on second
      generation antipsychotics is a cause for concern and suggests the need for
      further extensive follow-up and assessment of the problem.

PMID- 23868633
TI  - No association between catalase (CAT) gene polymorphisms and susceptibility to
      vitiligo in a Turkish population.
AB  - BACKGROUND AND AIMS: Vitiligo is an acquired hypomelanotic skin disorder
      resulting from the loss of functional melanocytes from the cutaneous epidermis.
      Low catalase (CAT) activity and Accumulation of hydrogen peroxide (H2O2) have
      been demonstrated in the epidermis of vitiligo patients. Some polymorphisms on
      catalase gene may have effect on the quantity and activity of catalase enzyme.
      The aim of this study was to investigate whether catalase (CAT) gene
      polymorphisms are associated with susceptibility to vitiligo in Turkish
      population. MATERIALS AND METHODS: One hundred and three patients with vitiligo
      and one hundred and seven gender, age and ethnic matched controls were enrolled
      in the study. Genotyping was done by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: The CAT gene -89A>T (rs7943316)
      and 389C>T (rs769217) genotypes and allele frequencies of vitiligo patients did
      not differ significantly from those of healthy controls. CONCLUSIONS: We found no
      association between CAT gene -89A>T and 389C>T polymorphism and vitiligo
      susceptibility in Turkish vitiligo patients. Further studies with greater sample
      size should be performed to verify these results.

PMID- 23868634
TI  - Examining cerebral metabolic abnormalities in chronic obstructive pulmonary
      disease (COPD) patients by localized proton magnetic resonance spectroscopy
      (MRS).
AB  - PURPOSE: The study was planned based on the hypothesis that cerebral metabolism
      is impaired in chronic obstructive pulmonary disease (COPD) by using localized in
      vivo proton magnetic resonance spectroscopy. MATERIALS AND METHODS: The study
      comprised 30 male patients, aged 45-70 years, with moderate level COPD and an
      aged matched group of 30 healthy males as the control group. Cerebral metabolism
      was investigated with proton magnetic resonance spectroscopy (MRS) using
      multivoxel technique. Data normal distribution conformity was evaluated by the
      One Sample Kolmogorov Smirnov Test and homogeneity by the One-Way ANOVA test. For
      both the COPD and control group, data were obtained as mean, standard deviations,
      minimum and maximum values. Independent sample t-test was used for the comparison
      of means between the two groups. RESULTS: The frontal and parietal white matter
      in patients with COPD showed an overall reduction in cerebral metabolites. The
      NAA (N-acetylaspartate)/Cr (Creatinine), Cho (Choline)/Cr ratios of the cerebral
      frontal and parietal white matter regions in the COPD group were significantly
      lower than the control group. CONCLUSIONS: The findings of this study through the
      use of MRS confirmed that most patients with symptomatic COPD have cerebral
      metabolic abnormalities.

PMID- 23868635
TI  - Ultrasound evaluation of bone in sport: the role of physical activity in young
      volleyball females players.
AB  - Physical activity represents an effective incentive to achieve and maintain the
      peak bone mass. Our study has been evaluating the heel ultra-sound parameters in
      a group of female volleyball players. We found some interesting results as
      follows: BMD estimated, 0.675+/-0.144 g/cm2; QUI 120.2+/-20.9; SOS 1590.4+/-32.3
      m/S; BUA 95.5+/-20.1 dB/ MHz. Each parameter observed on the volleyball players
      group has resulted significantly higher (p<0.05-0.01) compared to the same
      parameters within the control group. Our work confirms that an aerobic physical
      activity represents an effective mechanical stimulus to the bone, allowing of
      observing an index of bone quality significantly higher compared to the people
      who does not do any regular physical activity.

PMID- 23868636
TI  - Serum ceruloplasmin levels in acute decompensated heart failure.
AB  - BACKGROUND: Ceruloplasmin (Cp) is a serum protein that belongs to the family of
      alpha2-globulins and it is increased in patients with after acute myocardial
      infarction complicated with heart failure. Aim of the study was to investigate
      levels of serum Cp in patients with acute decompensated heart failure. MATERIALS
      AND METHODS: The present cross-sectional observational study consists of three
      groups: Fifty patients with decompensated heart failure (Group 1) and same 50
      patients after compensation (Group 2); 50 control patients group with comparable
      age and sex without heart failure (Group 3). Demographic, echocardiographic and
      biochemical data of patients were collected. Serum Cp level was determined
      spectrophotometrically. RESULTS: Serum ceruloplasmin was significantly increased
      in Groups 1 (820.8 +/- 78.5 IU/dL) and 2 (873.5 +/- 121.0 IU/dL) compared, to
      Group 3 (640.6 +/- 132.4 IU/dL) (p<0.001). In the sub-group analysis, this
      difference was due to the difference between Groups 3, Group 1 and 2 (both
      p=0.0001) whereas no significant difference was present between Group I and Group
      2 (p>0.063). A positive correlation was found between Cp and female sex, heart
      rate, systolic and diastolic blood pressure, acetylsalisilic acid and diuretic
      use, left ventricular systolic and diastolic diameter, mitral regurgitation, and
      negative correlation was found between Cp and ejection fraction (p<0.05 for all)
      whereas none of the parameters were independently associated with serum Cp level
      (p>0.05). CONCLUSIONS: Findings of the present study suggest that serum Cp level
      is increased in both decompensated and compensated HF compared to controls.
      Further large scale studies are needed to elucidate the pathophysiological
      mechanisms of increased Cp in HF.

PMID- 23868637
TI  - Intraoperative recurrent laryngeal nerve monitoring in thyroid surgery: is it
      really useful?
AB  - AIM: The aim of this study was to evaluate the ability of intraoperative
      recurrent laryngeal nerve monitoring to predict the postoperative functional
      outcome and the potential role of this technique in reducing the postoperative
      nerve palsy rate. MATERIALS AND METHODS: Between June 2007 and December 2011,
      1693 consecutive patients who underwent thyroidectomy by a single surgical team
      were evaluated. We compared patients who have had a neuromonitoring and patients
      who have undergone surgery with the only visualization. Patients in which NIM was
      not utilized (Group A) were 942 against the others 751 (group B). RESULTS: In
      group A there were 28 recurrent laryngeal nerve injuries (2.97%) of which 21 were
      transients (2.22%) and 7 were permanents (0.74%). In group B there were 20
      recurrent laryngeal nerve injuries (2.66%) of which 14 (1.86%) transients and 6
      (0.8%) permanents. Differences between the two groups were not statistically
      significative. CONCLUSIONS: The technique of intraoperative neuromonitoring in
      thyroid surgery is safe and reliable in excluding postoperative recurrent
      laryngeal nerve palsy; it has high accuracy, specificity, sensitivity and
      negative predictive value. Neuromonitoring is useful to identify the recurrent
      laryngeal nerve and it can be a useful adjunctive technique for reassuring
      surgeons of the functional integrity of the nerve but it does not decrease the
      incidence of injuries compared with visualization alone. Its application can be
      particularly recommended for high-risk thyroidectomies.

PMID- 23868638
TI  - Evaluation of the relationship between preeclampsia and seropositivity of
      infectious disease in maternal plasma.
AB  - PURPOSE: The aim of the present study was to investigate the association between
      maternal infections and preeclampsia. MATERIALS AND METHODS: Fifty-four pregnant
      women with preeclampsia (study group) and 54 healthy pregnant women (control
      group) were enrolled in this study. Chlamydia pneumoniae (CP), Mycoplasma hominis
      (MH), Helicobacter pylori (HP), Cytomegalovirus (CMV), Herpes simplex virus type
      2 (HSV-2), and Toxoplasma gondii (TG) antibodies were analyzed in the maternal
      plasma of all of the participants. RESULTS: There was no difference in the
      demographic data between groups. Maternal plasma seropositivity for CP IgM; MH
      IgA and IgG; HP IgM, IgA and IgG; TG, CMV and HSV-2 IgM and IgG were not
      significantly different between the preeclampsia and control groups. The
      seropositivity for CP IgG was significantly higher in women with preeclampsia
      versus the control women. CONCLUSIONS: Our results suggested that preeclampsia is
      associated with CP IgG seropositivity.

PMID- 23868639
TI  - [Inveterate squamous cell carcinoma of the upper eyelid: a case report].
AB  - Squamous cell carcinoma (SCC) is a malignant tumor of epithelium that shows
      squamous cell differentiation. It is the second most common cancer of the skin
      and usually occurs in areas exposed to the sun but it can rarely arise within the
      conjunctival epithelium with a deep component. We describe a woman with a history
      of chronic blepharoconjunctivitis unresponsive to topical medications.
      Examination disclosed a hyperaemic translucent patch with blurred margins of the
      upper palpebral conjunctiva. Tarsoconjunctival biopsy revealed intraepithelial
      squamous cell carcinoma. Management consisted of complete tumor excision with
      removal of the entire posterior lamella of the left upper eyelid and
      reconstruction. Histopathologic analysis confirmed primary squamous cell
      carcinoma arising from conjunctival epithelium, involving the underlying tarsus.
      Patients with unexplained chronic unilateral blepharoconjunctivitis or papillary
      hypertrophy of the palpebral conjunctiva should be considered for biopsy to rule
      out neoplasia, even when there is no sign of an evident mass.

PMID- 23868640
TI  - A case of sensitization to alitretinoin.
AB  - Alitretinoin is a unique retinoid authorised for the treatment of adults with
      severe chronic hand eczema (CHE) refractory to potent topical steroids. The most
      common adverse events (AEs) were typical class effects of oral retinoids
      including headache, flushing and skin disorders. To our knowledge, there are no
      cases of sensitization to alitretinoin reported in literature. We present a case
      of sensitization to alitretinoin.

PMID- 23868641
TI  - [Phenelzine: legacy or current psychiatric practice?].
AB  - Monoamine oxidase inhibitors (MAO-I) are the first drugs of antidepressant
      classes discovered. Phenelzine is a worldwide prescribed MAO-I, studied in a
      variety of mood and anxiety disorders. Purpose of the present paper is to
      critically review the results reported in the scientific international literature
      focusing on efficacy and safety of phenelzine in clinical psychiatric practice,
      in order to achieve a better understanding of the relationship between
      pharmacological data, therapeutic approach and side or adverse effects. We
      performed a careful PubMed (1980-2012) search on clinical pharmacology and
      clinical use of phenelzine in various psychiatric disorders. We reported our
      findings discussing separately clinical pharmacology data and systematic
      controlled, randomised and not randomised, clinical studies.

PMID- 23868642
TI  - [The role of lactate besides the lactic acidosis].
AB  - Lactic acidosis (LA) is the most common form of metabolic acidosis defined by
      values of lactate greater than 5 mmol / l and by a pH <7.34. The pathogenesis of
      LA involves hypoxic (type A) and non hypoxic (type B) causes which are often
      coexisting. Lactic acidosis is usual in hospitalized population especially in
      subjects in intensive care units, in which lactate levels on admission could be
      predictors of mortality even in the absence of organ dysfunction or shock. The
      outcome is mainly dependent on the cardiovascular effects of acidosis. In
      subjects with cardiogenic shock, the increased lactate/pyruvate ratio, detectable
      at onset, is correladed with mortality. An early assessment of blood and tissue
      lactate levels could play a role in the therapeutic management as well as in
      outcome. LA could be a unfavorable prognostic factor in cancer. The lactate would
      act also as "signal molecule" and as a promoting factor in angiogenesis and tumor
      progression. In the presence of risk factors for LA the role of metformin may be
      overrated. Despite the doctrinal progress to understand the pathogenesis and
      pathophysiology, there is not univocal consensus on the therapeutic treatment of
      LA. The identification and the attempt to remove the cause of acidosis are main
      aims; treatment with sodium bicarbonate is a matter of debate as the data on the
      cardiovascular effects and mortality are unclear. The therapy with carbicarb,
      dichloroacetate or THAM has shown no specific advantages in terms of mortality.
      In experimental models of LA and shock the use of sodium-hydrogen exchanger-1
      (NHE1) selective inhibitors reduces cell damage and inflammatory cytokines
      synthesis; it also improves cardiac performance and decreases mortality.

PMID- 23868643
TI  - [Substance use and victimization in violent assaults].
AB  - OBJECTIVES: The aim of this work was to examine the role of substance use as
      factor which increase risk of assault. MATERIALS AND METHODS: A review of the
      some of the most important international literature about drug-facilitated crimes
      is presented here. RESULTS: The whole part of the papers shows a relationship
      between substance use and risk increase of assault, particularly in family
      violence and rape. CONCLUSIONS: The effects of psychotropic substances use depend
      on the user's emotional state and on drugs use expectations. This prospective
      shows that we need to be cautious in interpreting processes of linear causality
      between abusive behaviour, processes of victimisation, abuses and abnormal sexual
      behaviours, which are related to the patient's desires, enhanced and validated by
      drugs.

PMID- 23868644
TI  - Alternative-based thresholding with application to presurgical fMRI.
AB  - Functional magnetic reasonance imaging (fMRI) plays an important role in pre
      surgical planning for patients with resectable brain lesions such as tumors. With
      appropriately designed tasks, the results of fMRI studies can guide resection,
      thereby preserving vital brain tissue. The mass univariate approach to fMRI data
      analysis consists of performing a statistical test in each voxel, which is used
      to classify voxels as either active or inactive-that is, related, or not, to the
      task of interest. In cognitive neuroscience, the focus is on controlling the rate
      of false positives while accounting for the severe multiple testing problem of
      searching the brain for activations. However, stringent control of false
      positives is accompanied by a risk of false negatives, which can be detrimental,
      particularly in clinical settings where false negatives may lead to surgical
      resection of vital brain tissue. Consequently, for clinical applications, we
      argue for a testing procedure with a stronger focus on preventing false
      negatives. We present a thresholding procedure that incorporates information on
      false positives and false negatives. We combine two measures of significance for
      each voxel: a classical p-value, which reflects evidence against the null
      hypothesis of no activation, and an alternative p-value, which reflects evidence
      against activation of a prespecified size. This results in a layered statistical
      map for the brain. One layer marks voxels exhibiting strong evidence against the
      traditional null hypothesis, while a second layer marks voxels where activation
      cannot be confidently excluded. The third layer marks voxels where the presence
      of activation can be rejected. 

PMID- 23868645
TI  - Simultaneous determination of atropine, scopolamine, and anisodamine in Flos
      daturae by capillary electrophoresis using a capillary coated by graphene oxide.
AB  - A novel CE method was developed for the separation and determination of three
      main tropane alkaloids in Flos daturae with a capillary coated by graphene oxide
      (GO). The GO-coated capillary was characterized by SEM, energy dispersive X-ray
      spectroscopy, and Raman spectroscopy, and the results indicated that the inner
      surface of the capillary was partially coated by GO. A phosphate solution (40 mM,
      pH7.0) containing 20% v/v methanol and 30% v/v acetonitrile was used as the
      running buffer for the analysis of the atropine, scopolamine, and anisodamine.
      The linear ranges of atropine, scopolamine, and anisodamine was 0.5-200 MUg/mL
      with satisfactory correlation coefficients (R(2)) > 0.9987, and this novel method
      provided an efficient separation for three tropane alkaloids as well as a good
      reproducibility and stability. Finally, the method was successfully applied for
      the determination of these three tropane alkaloids in plant extracts.

PMID- 23868646
TI  - [Which non-clinical factors influence the use of innovative implants? The example
      of drug-releasing coronary stents in patients with acute myocardial infarction: a
      multilevel regression analysis].
AB  - BACKGROUND AND PURPOSE: The aim of this paper is to identify characteristics that
      inhibit or encourage the diffusion of novel implants in the German health care
      system using the example of drug-eluting stents (DES). After their introduction
      in the early 2000s, DES were considered as an effective innovative technology.
      Hypotheses that link the use of DES to characteristics on patient-level, hospital
      level, regional-level as well as on state-level are generated on existing
      literature. These hypotheses are tested using administrative data from a German
      sickness fund. METHODS: The analysis is based on the administrative sickness fund
      data of 6 777 patients with a hospital admission due to an acute myocardial
      infarction (AMI) and an implantation of either a DES or a bare-metal stent. The
      sickness fund data was merged with information on reimbursement surcharges for
      DES implantations, information from the German Hospital Registry and information
      on county level provided by the German National Statistical Office. Logistic
      regressions with random intercepts on hospital and county level as well as fixed
      effects on state level were estimated to identify characteristics that are
      correlated with DES use. RESULTS: All levels do have an impact on the treatment
      decision whereas the patient-level is of major importance. In particular, young
      age, admission to a university or a privately owned hospital and a hospital
      located in a county with a low level of bankruptcies are positively correlated
      with DES use. CONCLUSION: Although individual characteristics are of major
      importance for DES use in the German health care system, characteristics at the
      hospital and regional level do have an impact on the use of DES. Further research
      on the influence of reimbursement mechanisms in the German setting is needed.

PMID- 23868647
TI  - [Promotion of fruit and vegetable consumption among school children--mission
      (im)possible?].
AB  - A diet rich in fruits and vegetables in school children is important for the
      physical and cognitive development of the child as well as for the prevention of
      nutrition-related diseases. In Germany, 816 school children (boys and girls, aged
      10-13 years) from 14 public schools in the state of Hesse were interviewed about
      their fruit and vegetable intake in May 2009. The subsequent intervention was
      conducted between November 2009 and April 2010 among 7 schools. The intervention
      group received work sheets on fruit and vegetables and had additional promotional
      and educational activities. The other schools served as controls. After the
      intervention period, a follow-up survey was carried out in all schools. Both
      surveys used the same standardised questionnaire for assessing the fruit and
      vegetable consumption. Comparison between baseline survey and follow-up showed no
      change in consumption amount among the children of the intervention group. In the
      control group, fruit consumption decreased statistically significantly (p=0.034).
      The intervention positively impacted on the diversity of consumed fruit and
      vegetables. The strategies of PRO GREENS provide a basis for the promotion of
      fruit and vegetable consumption among school children. They need to be further
      improved regarding the participation of parents, practical relevance, situational
      prevention, and long-lasting cooperation to ensure a diversified dietary and
      nutrient intake.

PMID- 23868648
TI  - [The impact of migration background on children's secondhand smoke exposure. A
      cross-sectional study within the health monitoring units (GME) in Bavaria,
      Germany].
AB  - AIM OF THE STUDY: Differences in children's secondhand smoke (SHS) exposure were
      examined by migration-specific characteristics, socioeconomic factors and living
      conditions, as well as with regard to the parents SHS knowledge and SHS
      attitudes. STUDY POPULATION AND METHODS: Data from 5,336 pre-school children (29%
      migrants) were collected in a cross-sectional study in 2008/2009 in Germany
      through parental questionnaire (response rate: 61%). Using multiple logistic
      regression, the association of migration background and children's SHS exposure
      was analysed. RESULTS: Children with a migration background are at an increased
      risk of SHS exposure in their homes. Multivariate analyses show that adjusting
      for socioeconomic factors and parental knowledge of how to protect their children
      from SHS reduces the estimates of migration background significantly. Compared to
      children without migration background, the chance of SHS exposure for children
      with migration background is still increased (OR [95% CI]: 1.57 [1.23-2.01]).
      Children of Turkish-speaking families, compared to children from German-speaking
      families, are most often burdened by SHS (3.05 [2.18-4.26]). CONCLUSION: Migrant
      sensitive tobacco prevention in selected risk groups is necessary to provide
      support for creating smoke-free homes for children.

PMID- 23868649
TI  - [Patients' perspectives beyond sectoral borders between inpatient and outpatient
      care - patients' experiences and preferences along cross-sectoral episodes of
      care].
AB  - AIM: Patient perspective is crucial concerning health care and quality
      improvement. During episodes of care, patients come into contact with
      multidisciplinary health-care providers in inpatient and outpatient settings and
      are in a unique position to describe processes throughout the entire chain of
      care. The aim of this study was to identify patients' experiences and preferences
      with fragmented cross-sectoral care to develop a patient-centred cross-sectoral
      quality-assessment instrument. METHOD: Patient perspective was analysed using
      qualitative focus-group methods. Patients were recruited from general practices
      if they had experienced cross-sectoral care. Focus group discussions were
      audiotaped, transcribed and analysed using ATLAS.ti software. Categories were
      extracted deductively according to a previously developed focus group guide and
      supplemented by inductive analyses. RESULTS: Patients identified quality gaps
      mainly concerning communication and coordination of care mostly along the cross
      sectoral interfaces. Referrals and hospitalisations were characterised by
      redundant examinations and deficits in forwarding clinical findings. Support and
      organisation of follow-up care was rated to be improvable mainly during inpatient
      care and discharge. Patients identified also quality deficits concerning
      inpatient hygiene factors and changes of medication. Lack of transparency and
      responsibility within the entire chain of care caused anxiety and unstableness of
      patients. CONCLUSION: Patients' experiences provide important information to
      identify quality gaps along the entire chain of care. Study results can be used
      to develop a cross-sectoral patient-centred quality assessment instrument.

PMID- 23868650
TI  - [Which medical errors do general practitioners make? Data from the Expert
      Arbitration and Advisory Board of the Baden-Wurttemberg State Medical
      Association].
AB  - BACKGROUND: In Germany, medical error reporting systems are well established.
      They collect information reported principally by physicians. Systematic data
      collection concerning medical errors is also performed by expert arbitration and
      advisory boards of the German State Medical Associations. METHODS: Data base MERS
      (Medical Error Reporting System); cases from the Expert Arbitration and Advisory
      Board of the State Baden-Wurttemberg from the years 2004-2011 (8,042 cases) were
      evaluated as follows: extraction of the cases from general practitioners (n=307,
      4%); categorisation of the type of error and degree of severity; classification
      according to ICD-10 (International Classification of Diseases); overview of
      confirmed cases including commentaries of the above board; logistic regression
      analysis of factors potentially associated with confirmed cases. RESULTS: In 26%
      (n=80) the board confirmed medical errors. 55% of the errors were assigned to the
      category "diagnosis" (n=44), 21% to "general therapy" (n=17), 8% to "operative
      therapy" ("minor surgical operations") (n=6) and 10% to "injections" (n=8). 29%
      of cases (n=23) were associated with permanent damage or death. The majority of
      cases could be assigned to ICD-10 categories "I" (cardiovascular system, n=20)
      and "S-T" or "V-Y" (consequences of external causes or external causes of
      morbidity and mortality, n=34). No significant associations were found by
      logistic regression analysis. CONCLUSION: The rate of confirmed cases corresponds
      with the rate of all medical disciplines. The presented overview is illustrative
      and may be of help to avoid errors by using it for continuing medical education.

PMID- 23868652
TI  - [Validation of the German version of the Singing Voice Handicap Index].
AB  - The Singing Voice Handicap Index (SVHI) was developed in the United States for
      the self-assessment of patients with singing problems. It has been translated
      into German and its reliability and validity have been assessed. In total, 54 (35
      female, 19 male) dysphonic singers and 130 (74 female, 56 male) non-dysphonic
      professional singers were included in the study. Reliability rested on high test
      retest reliability (r = 0.960, p <= 0.001, Pearson correlation) and a Cronbach's
      alpha of 0.975. A principal component analysis using the Varimax method and the
      results of the screeplot suggest the SVHI scored as a single scale. Validity
      rested on a highly significant correlation between the severity of the self-rated
      voice impairment by the patient and the total SVHI score. Dysphonic singers have
      significantly higher SVHI scores than healthy singers. The SVHI is thus suited to
      implementation as a diagnostic tool in German-speaking countries. 

PMID- 23868651
TI  - [Sexual risk behaviour of nursing students. A cross-sectional study at nursing
      schools in Saxony-Anhalt].
AB  - AIM: This work describes the sexual risk behaviour of nursing students. METHODS:
      22 of 23 state-approved nursing schools in Saxony-Anhalt, Germany, participated
      in this cross-sectional study (study period 7/2005-5/2006). Participation was
      voluntarily and anonymous. RESULTS: More male than female students (59.6% vs.
      44.8%) used condoms to prevent STIs. More female students (58.9% vs. 43.4%)
      reported constant partnership with just one partner as an STI prevention method
      (chi2 test, p<0.005). 29.6% of the nursing students reported >1 sexual partner in
      the past 12 months. 3.9% of the students demanded an HIV test from the partner,
      69.3% had never tested themselves for HIV. 10.2% used no prevention against STIs.
      CONCLUSIONS: Nursing students should be sensitised for sexual risk behaviour and
      STIs. This should be included in the content of teaching throughout the
      education, not least since nursing students are multiplicators and have an
      influence on health behaviour of the patients.

PMID- 23868653
TI  - [Middle ear salivary gland choristoma related to branchio-oto-renal syndrome
      diagnosed by array-CGH].
AB  - Branchio-oto-renal (BOR) syndrome is characterized by ear malformations
      associated with sensorineural or mixed hearing loss. In addition, preauricular
      tags, preauricular pits, branchial cleft fistulas and cysts, as well as renal
      dysplasia are seen. A genetic mutation on chromosome 8, either autosomal
      dominantly inherited or occuring as a spontaneous mutation, is the cause in the
      majority of cases. Using array-based comparative genomic hybridization (CGH), it
      is possible to detect even the smallest genetic changes. Salivary gland
      choristoma in the middle ear is very rare. Surgical removal and histological
      clarification are required. 

PMID- 23868654
TI  - [Liposomal local therapy as treatment for sicca symptoms in patients with primary
      Sjogren's syndrome].
AB  - BACKGROUND: Primary Sjogren's syndrome (pSS) represents the most common
      rheumatologic disease in the head and neck area. Due to various nonspecific
      symptoms, many different medical specialities are involved in diagnostic and
      therapeutic regimes of patients with pSS. Therefore broad knowledge of symptoms
      and therapeutic options is important. Effective management of xerostomia,
      keratoconjunctivis sicca (KCS), and rhinitis sicca (RS) is essential in every
      patient to alleviate symptoms and prevent local complications. Various
      substitutes with different ingredients are available for topical and symptomatic
      therapy, but there are no generally accepted treatment suggestions due to the
      lack of studies proving effective relief of symptoms. MATERIAL AND METHODS:
      Between October 2007 and August 2012, pSS was diagnosed in 73 patients according
      to the American European Consensus Group (AECG) criteria. Before and after a 2
      month period of treatment with liposomal agents for oral, nasal, and ocular
      complaints (LipoSaliva(r), LipoNasal(r), and Tears Again(r),) AECG criteria and
      subjective symptoms were evaluated using visual analogue scales. RESULTS:
      Xerostomia (92 %), KCS (92 %), and recurrent salivary gland swelling (40 %) were
      the leading clinical symptoms. Mean salivary flow rate was 1.89 g (Saxon test),
      mean lacrimal flow 12.7 mm (Schirmer I test). SS-A and -B antibodies could be
      detected in 47 patients (29 %). An average histologic focus score of 3 was
      assigned (Chisholm and Mason). Extraglandular manifestations were observed in 17
      %, while severe local complications due to ineffective treatment of sicca
      symptoms were diagnosed in 70.5 %. Liposomal local therapy caused a significant
      reduction of xerostomia (p = 0.0001), KCS (p = 0.004), and RS (p = 0.004).
      CONCLUSION: Local therapy with liposomal agents is effective in the symptomatic
      treatment of xerostomia, KCS, and RS in patients with pSS.

PMID- 23868655
TI  - Operative risks associated with contralateral prophylactic mastectomy: a single
      institution experience.
AB  - BACKGROUND: The purpose of this study was to determine if newly diagnosed breast
      cancer patients undergoing contralateral prophylactic mastectomy (CPM) experience
      more complications than patients undergoing unilateral mastectomy (UM). METHODS:
      A total of 600 patients underwent either UM or CPM between January 2009 and March
      2012 for unilateral breast cancer. Operative complications were classified as
      minor (aspirations, infection requiring antibiotics, partial flap and nipple
      necrosis, minor bleeding, delayed wound healing) or major (hematoma or seroma
      requiring operation, infection requiring rehospitalization, blood product
      transfusion, total flap or nipple loss, implant removal), mixed (both minor and
      major complications), or multiple. Chi-square and multivariate logistic
      regressions were used for the analysis. RESULTS: Of the 600 patients, 391 (65 %)
      underwent UM and 209 (35 %) underwent CPM. Across all complication groups, there
      were significantly more complications in the CPM group versus the UM group (41.6
      vs. 28.6 %, p = 0.001). Major complications alone were significantly greater in
      the CPM versus the UM group (13.9 vs. 4.1 %, p < 0.001). When adjusting for age,
      body mass index, smoking and diabetes history, AJCC stage, reconstruction,
      previous radiation therapy, and adjuvant therapy, CPM patients were 1.5 times
      more likely to have any complication (odds ratio [OR] 1.53; 95 % CI 1.04-2.25, p
      = 0.029) and 2.7 times more likely to have a major complication compared with UM
      patients (OR 2.66; 95 % CI 1.37-5.19, p = 0.004). CONCLUSIONS: CPM patients have
      an increased risk of complications, especially major complications requiring
      rehospitalization or reoperation. These complications may influence patient and
      physician decisions to choose CPM.

PMID- 23868656
TI  - A model-based approach to characterize the population pharmacokinetics and the
      relationship between the pharmacokinetic and safety profiles of RBP-7000, a new,
      long-acting, sustained-released formulation of risperidone.
AB  - RBP-7000 is a sustained-release (once-monthly injection for subcutaneous
      administration) formulation of risperidone using the ATRIGEL(r) Delivery System,
      developed for treatment of schizophrenia to address compliance issues associated
      with oral administration. The objective of this analysis was to report the
      results of a population pharmacokinetic analysis and to describe the relationship
      between risperidone and 9-hydroxyrisperidone levels with dopamine (DA) D2
      receptor occupancy, prolactin levels, and adverse events using data collected in
      45 clinically stable schizophrenic patients receiving RBP-7000 in single
      ascending doses (risperidone) of 60, 90, and 120 mg. The population PK model
      accounted for an initial peak, a delayed and slow delivery, the disposition of
      risperidone, and the conversion of risperidone to 9-hydroxyrisperidone. BMI was a
      covariate affecting absorption of risperidone and ultimately formation of 9
      hydroxyrisperidone. A logistic analysis indicated a correlation between the
      increase in Active Moiety (risperidone + 9-OH-risperidone) exposure (Cmax ) and
      the probability of observing GI disorders. An Emax population PK/prolactin model
      best described the relationship between the circulating Active Moiety and the
      serum prolactin levels. Gender was a significant covariate associated with Emax .
      These data provided a comprehensive characterization of the relationship between
      circulating Active Moiety and the efficacy/safety profile of RBP-7000 in
      clinically stable schizophrenic patients. 

PMID- 23868658
TI  - Salt melt synthesis of ceramics, semiconductors and carbon nanostructures.
AB  - Materials synthesis in the liquid phase, or wet-chemical synthesis, utilizes a
      solution medium in which the target materials are generated from a series of
      chemical and physical transformations. Although this route is central in organic
      chemistry, for materials synthesis the low operational temperature range of the
      solvent (usually below 200  degrees C, in extreme 350  degrees C) is a serious
      restriction. Here, salt melt synthesis (SMS) which employs a molten inorganic
      salt as the medium emerges as an important complementary route to conventional
      liquid phase synthesis. Depending on the nature of the salt, the operational
      temperature ranges from near 100  degrees C to over 1000  degrees C, thus
      allowing the access to a broad range of inorganic crystalline materials and
      carbons. The recent progress in SMS of inorganic materials, including oxide
      ceramic powders, semiconductors and carbon nanostructures, is reviewed here. We
      will introduce in general the range of accessible materials by SMS from oxides to
      non-oxides, and discuss in detail based on selected examples the mechanisms of
      structural evolution and the influence of synthetic conditions for certain
      materials. In the later sections we also present the recent developments in SMS
      for the synthesis of organic solids: covalent frameworks and polymeric
      semiconductors. Throughout this review, special emphasis is placed on materials
      with nanostructures generated by SMS, and the possible modulation of materials
      structures at the nanoscale in the salt melt. The review is finalized with the
      summary of the current achievements and problems, and suggestions for potential
      future directions in SMS. 

PMID- 23868657
TI  - Nanosensor dosimetry of mouse blood proteins after exposure to ionizing
      radiation.
AB  - Giant magnetoresistive (GMR) nanosensors provide a novel approach for measuring
      protein concentrations in blood for medical diagnosis. Using an in vivo mouse
      radiation model, we developed protocols for measuring Flt3 ligand (Flt3lg) and
      serum amyloid A1 (Saa1) in small amounts of blood collected during the first week
      after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations
      showed excellent dose discrimination at >= 1 Gy in the time window of 1 to 7 days
      after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first
      two days after exposure. A multiplex assay with both proteins showed improved
      dose classification accuracy. Our magneto-nanosensor assay demonstrates the dose
      and time responses, low-dose sensitivity, small volume requirements, and rapid
      speed that have important advantages in radiation triage biodosimetry. 

PMID- 23868659
TI  - Total syntheses of (+/-)-spiroquinazoline, (-)-alantryphenone, (+)-lapatin A, and
      (-)-quinadoline B.

PMID- 23868660
TI  - Induction of apoptosis by antimycin A in differentiated PC12 cell line.
AB  - Antimycin A (AMA) is an inhibitor of mitochondrial electron transport chain via
      binding to mitochondrial complex III. This inhibition increases the production of
      reactive oxygen species (ROS). The aim of the present study was to investigate
      the effect of AMA on PC12 cells in vitro. Results of the nuclear morphology and
      the flow cytometer indicated that AMA efficiently induced PC12 cell apoptosis.
      Moreover, the levels of ROS and Ca(2+) increased in the early stage of cell
      apoptosis induced by AMA treatment. All of Ca(2+) chelators, L-type Ca(2+)
      channel blockers and inhibitors of Ca(2+) released from endoplasmic reticulum and
      ROS scavenger, were used in this experiment. It was found that the Ca(2+)
      chelators and ROS scavengers, in particular, could delay AMA-induced PC12 cell
      apoptosis. In conclusion, the present study found that AMA induced PC12 cell
      apoptosis through ROS and Ca(2+).

PMID- 23868661
TI  - Do e-cigarettes have the potential to compete with conventional cigarettes?: a
      survey of conventional cigarette smokers' experiences with e-cigarettes.
AB  - BACKGROUND: Electronic cigarettes (ECs) are becoming increasingly popular
      globally. If they were to replace conventional cigarettes, it could have a
      substantial impact on public health. To evaluate EC's potential for competing
      with conventional cigarettes as a consumer product, we report the first data, to
      our knowledge, on the proportion of smokers who try ECs and become regular users.
      METHODS: A total of 2,012 people seen smoking or buying cigarettes in the Czech
      Republic were approached to answer questions about smoking, with no mention made
      of ECs to avoid the common bias in surveys of EC users. During the interview, the
      volunteers' experience with ECs was then discussed. RESULTS: A total of 1,738
      smokers (86%) participated. One-half reported trying ECs at least once. Among
      those who tried ECs, 18.3% (95% CI, 0.15.7%-20.9%) reported using them regularly,
      and 14% (95% CI, 11.6%-16.2%) used them daily. On average, regular users used ECs
      daily for 7.1 months. The most common reason for using ECs was to reduce
      consumption of conventional cigarettes; 60% of regular EC users reported that ECs
      helped them to achieve this. Being older and having a more favorable initial
      experience with ECs explained 19% of the variance in progressing to regular EC
      use. CONCLUSIONS: Almost one-fifth of smokers who try ECs once go on to become
      regular users. ECs may develop into a genuine competitor to conventional
      cigarettes. Government agencies preparing to regulate ECs need to ensure that
      such moves do not create a market monopoly for conventional cigarettes.

PMID- 23868662
TI  - [Safety measures for trampolines cannot prevent severe injuries].
AB  - BACKGROUND: The number of injuries caused by accidents while springing on a
      trampoline has increased significantly. This study therefore focused on the
      incidence, morbidity and circumstances of the accidents in pediatric patients.
      METHODS: The children admitted to this hospital from 2002 to 2010 were re
      examined and the children injured during trampolining were asked to fill out a
      questionnaire focusing on the mechanism of the injury and the circumstances.
      RESULTS: A total of 268 accidents were included in the study and 28% of the
      injuries were severe (e.g. fracture, luxation and rupture). If there were special
      safety measures (e.g. safety net, floor mats, surrounding water 63%) 28.4% of the
      injuries were severe and without safety measures 28.6% were severe. Safety
      measures did not influence the incidence of severe trauma (p=1). If a trampoline
      was equipped with a safety net (53%) 31% of the injuries were severe and without
      a safety net 25% were severe (p=0.473). CONCLUSION: Pediatric accidents on a
      trampoline result in severe injuries in 28% of cases. There is no difference in
      the severity of the injury regarding trampolines with or without special safety
      measures. Safety nets do not reduce the risk of severe injury.

PMID- 23868664
TI  - [Uveitis].

PMID- 23868663
TI  - Dose-dependent bioavailability indicators for curcumin and two of its novel
      derivatives.
AB  - Novel water-soluble curcumin derivatives have been developed to overcome low in
      vivo bioavailability of curcumin. The aim of this work is to assess the potential
      utility of certain downstream targets as bioavailability indicators of systemic
      activity of pure curcumin and two novel water-soluble curcumin derivatives (NCD)
      by constructing dose-dependent response curves and to prove whether this novel
      curcumin derivatives retained, improved, or abolished biological activity of pure
      curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative
      (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats
      at escalating doses: 37, 74, 148, and 296 MUM/kg body weight, respectively.
      Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic
      activity of both HO-1 and GST were assessed one and half and 24 hours after oral
      administration of curcumin formulae. This study showed that there was a
      progressive elevation of cavernous tissue levels of cGMP and enzymatic activity
      of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with
      CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on
      the curve. The three dose-dependent bioavailability indicators as surrogates of
      curcumin and two of its novel derivatives are valid in the studied range of
      concentration and extended time. The novel curcumin derivatives still conserve
      with improvement the biological activity of natural curcumin when applied in
      vivo.

PMID- 23868665
TI  - [Corneal surgery. Avoidance of complications is better than treatment of
      complications].

PMID- 23868666
TI  - [Avoidance and management of complications in laser in situ keratomileusis].
AB  - Laser in situ keratomileusis (LASIK) is now considered to be a safe and effective
      standard procedure for surgical correction of low to medium ametropia.
      Nevertheless, as in any other surgical intervention complex courses may occur in
      single rare cases. Possible complications include, but are not limited to,
      optically effective errors, such as too small or decentered optical zones as well
      as intraoperative flap cutting errors and postoperative complications, such as
      inflammation (e.g. diffuse lamellar keratitis, DLK), epithelial or flap folds,
      epithelial ingrowths or iatrogenic ectasia. Compliance to standards for
      indications and treatment based on the current scientific knowledge can
      significantly reduce the occurrence of complications. These standards include
      adjustment of the optical zone to the mesopic pupil diameter, the application of
      state of the art eye trackers, careful performance of intraoperative and
      postoperative procedures by a surgeon experienced in the entire spectrum of
      ocular surgery, the possibility of treating complications directly on occurrence
      and, last but not least, conservative patient selection and choice of treatment. 

PMID- 23868667
TI  - [Current state of refractive surgery of the cornea and lens].
AB  - Refractive surgery includes all procedures which are primarily targeted at
      changing the refractive power of the eye. Currently laser-assisted in situ
      keratomileusis (LASIK) is indicated to correct myopia of up to - 8 D, hyperopia
      up to + 3 D and astigmatism up to 5 D. Photorefractive keratectomy (PRK) and
      laser epithelial keratomileusis (LASEK) are primarily recommended for myopia up
      to - 6 D and for greater refractive errors, phakic intraocular lenses (IOL) are
      the first choice (myopia greater than - 6 D and hyperopia greater than + 3 D). If
      presbyopia is present in addition to the high refractive error, refractive lens
      exchange is another alternative. 

PMID- 23868669
TI  - Surface tectonics of nanoporous networks of melamine-capped molecular building
      blocks formed through interface Schiff-base reactions.
AB  - Control over the assembly of molecules on a surface is of great importance for
      the fabrication of molecule-based miniature devices. Melamine (MA) and molecules
      with terminal MA units are promising candidates for supramolecular interfacial
      packing patterning, owing to their multiple hydrogen-bonding sites. Herein, we
      report the formation of self-assembled structures of MA-capped molecules through
      a simple on-surface synthetic route. MA terminal groups were successfully
      fabricated onto rigid molecular cores with 2-fold and 3-fold symmetry through
      interfacial Schiff-base reactions between MA and aldehyde groups. Sub-molecular
      scanning tunneling microscopy (STM) imaging of the resultant adlayer revealed the
      formation of nanoporous networks. Detailed structural analysis indicated that
      strong hydrogen-bonding interactions between the MA groups persistently drove the
      formation of nanoporous networks. Herein, we demonstrate that functional groups
      with strong hydrogen-bond-formation ability are promising building blocks for the
      guided assembly of nanoporous networks and other hierarchical 2D assemblies. 

PMID- 23868668
TI  - Induction mortality, ATRA administration, and resource utilization in a
      nationally representative cohort of children with acute promyelocytic leukemia in
      the United States from 1999 to 2009.
AB  - BACKGROUND: Limited data exist on induction mortality of pediatric patients with
      acute promyelocytic leukemia in the United States, usage of all-trans retinoic
      acid (ATRA) during acute promyelocytic leukemia induction, and the resources
      needed to deliver induction therapy. PROCEDURE: Using the Pediatric Health
      Information System database we established a retrospective cohort of patients
      treated for newly diagnosed acute promyelocytic leukemia with ATRA between
      January 1999 and September 2009 in 32 of 43 PHIS contributing free-standing
      pediatric hospitals in the United States. Standard statistical methods were used
      to determine in-hospital induction mortality, ATRA administration, and resource
      utilization during a 60-day observation period. RESULTS: A total of 163 children
      were identified who met eligibility criteria for cohort inclusion; 52% were
      female and 76% were white with an average age of 12.7 years. A total of 12
      patients (7.4%) died, with 7 (58.3%) dying within the first 7 days of first
      admission. The mean time to first ATRA exposure increased with decreasing age (P
      = 0.0016). Resource utilization for management of retinoic acid syndrome was
      higher than anticipated based on prior studies and differed significantly from
      patients with non-M3 acute myeloid leukemia. CONCLUSIONS: The induction mortality
      for pediatric acute promyelocytic leukemia remains substantial with wide
      variation in ATRA administration and high rates of resource utilization.

PMID- 23868670
TI  - Strategies for ascertaining the interference of phase II metabolites co-eluting
      with parent compounds using LC-MS/MS.
AB  - LC-MS/MS is currently the most selective and efficient tool for the quantitative
      analysis of drugs and metabolites in the pharmaceutical industry and in clinical
      assays. However, phase II metabolites sometimes negatively affect the selectivity
      and efficiency of the LC-MS/MS method, especially for the metabolites that
      possess similar physicochemical characteristics and generate the same precursor
      ions as their parent compounds due to the in-source collision-induced
      dissociation during the ionization process. This paper proposes some strategies
      for examining co-eluting metabolites existing in real samples, and further
      assuring whether these metabolites could affect the selectivity and accuracy of
      the analytical methods. Strategies using precursor-ion scans and product-ion
      scans were applied in this study. An example drug, namely, caffeic acid phenethyl
      ester, which can generate many endogenous phase II metabolites, was selected to
      conduct this work. These metabolites, generated during the in vivo metabolic
      processes, can be in-source-dissociated to the precursor ions of their parent
      compounds. If these metabolites are not separated from their parent compounds,
      the quantification of the target analytes (parent compounds) would be influenced.
      Some metabolites were eluted closely to caffeic acid phenethyl ester on LC
      columns, although long columns and relatively long elution programs were used.
      The strategies can be utilized in quantitative methodologies that apply LC-MS/MS
      to assure the performance of selectivity, thus enhancing the reliability of the
      experimental data. 

PMID- 23868671
TI  - Posttraumatic stress disorder symptom clusters, alcohol misuse, and women's use
      of intimate partner violence.
AB  - Exploring how PTSD and alcohol misuse relate to women's use of intimate partner
      violence (IPV) is vital to develop our understanding of why some women may engage
      in IPV, which can serve to maximize intervention efforts for women. This study
      examined the extent to which posttraumatic stress disorder (PTSD) symptom
      clusters are directly and indirectly related to women's use of IPV through
      pathways involving alcohol misuse while controlling for severity of women's IPV
      victimization. The sample was comprised of substance-using, low socioeconomic
      status community women (N = 143) currently experiencing IPV victimization. The
      majority of the sample was African American (n = 115, 80.42%). This sample had an
      average annual household income of $14,368.68 (SD = $12,800.68) and the
      equivalent of a high school education (11.94 years, SD = 1.32). Path analyses
      indicated that the strongest statistical relationship emerged between women's use
      of IPV and women's IPV victimization. PTSD reexperiencing and numbing symptom
      severity was related to women's use of psychological, minor physical, and severe
      physical IPV; however, these relationships were indirect through alcohol misuse.
      Findings lend preliminary support for the application of the self-medication
      hypothesis to the study of PTSD, alcohol misuse, and IPV among women. 

PMID- 23868672
TI  - Reactive/proactive aggression and the development of internalizing problems in
      males: the moderating effect of parent and peer relationships.
AB  - The current study examined whether reactive and/or proactive aggression in
      adolescent males prospectively predicted increased levels of internalizing
      symptoms (depression and anxiety) in late adolescence. It was postulated that
      reactive aggression would be robustly related to later internalizing problems,
      but only among adolescent males who had problematic family or peer social
      relationships. Participants were a racially diverse group of 289 adolescent males
      (Mean age = 16). Measures of reactive and proactive aggression, peer rejection,
      and poor parent-adolescent communication were examined as predictors of both
      depression and anxiety symptoms assessed approximately 3 years later. The
      interactive effects between the two facets of aggression and measures of peer
      rejection and poor parent-adolescent communication in predicting internalizing
      problems was also examined. Adolescents with high levels of reactive aggression
      were more likely to exhibit elevated internalizing problems during late
      adolescence, even when controlling for pre-existing levels of anxiety/depression.
      However, this association only emerged for adolescents who had high levels of
      peer rejection and/or poor communication with their parent. Consistent with
      expectations, proactive aggression was unrelated to internalizing symptoms
      regardless of social relationship quality. Adolescent reactive, but not
      proactive, aggression is a risk factor for the development of internalizing
      problems. However, the findings suggest that interventions designed to foster
      positive social relationships among reactively aggressive youth may help protect
      them from developing significant internalizing problems over time.

PMID- 23868673
TI  - Development and measurement properties of the Dutch version of the Stanford
      Presenteeism Scale (SPS-6).
AB  - OBJECTIVE: To develop a Dutch version of the Stanford Presenteeism Scale (SPS-6)
      and examine the reliability and discriminant, discriminative and structural
      validity of the Dutch SPS-6 (DSPS-6). METHODS: The original SPS-6 (English
      language) was translated and adapted to the Dutch culture. Thirty participants
      filled in the DSPS-6 at baseline (T0) and after 5 days (T1). Internal consistency
      (Cronbach's alpha), test-retest reliability (Spearman's correlation coefficient,
      Spearman's rho), item-to-total correlations, discriminant validity (association
      with job stress and job satisfaction), discriminative validity (patients
      reporting a (work) disability compared with those indicating that they had no
      disability; Spearman's rho, t tests), structural validity (Varimax rotation with
      Kaiser Normalization) and floor and ceiling effects were examined. RESULTS:
      Cronbach's alpha for the DSPS-6 was 0.89. Test-retest Spearman's rho was 0.82 (p
      < 0.01). Item-to-total correlations ranged from 0.60 to 0.82. Subjects reporting
      a work disability had significantly lower DSPS scores (discriminative validity).
      Spearman's rho for the DSPS-6 score and job satisfaction were 0.38 (p = 0.05; at
      T0) and 0.27 (at T1), respectively. Spearman's rho for the association between
      the DSPS-6 and job stress were -0.52 (p = 0.01; at T0) and -0.42 (p = 0.05; at
      T1), respectively (discriminant validity). The two factors derived from the
      principal components analysis account for 77.5 % of the variance of responses
      (structural validity). A ceiling effect was present. CONCLUSIONS: The DSPS-6
      showed good reliability and structural validity. The discriminative validity of
      the DSPS-6 is partly supported. The concept of presenteeism is not sufficiently
      distinct from the constructs of job stress and job satisfaction (discriminant
      validity). The results of the present study show that the adaptation of the SPS-6
      into Dutch was successful. Further research on the reliability, validity and
      responsiveness of the DSPS-6 in a larger group of participants is recommended.

PMID- 23868674
TI  - Systemic light-chain amyloidosis presenting with rapid progressive heart failure.
AB  - Systemic amyloid light-chain (AL) amyloidosis is caused by deposition of
      immunoglobulin light-chain proteins. AL amyloidosis is a rapidly progressive
      disease that affects multiple organs. Cardiac involvement is frequent (50%) and
      the median survival is 5 months following diagnosis. Although transthoracic
      echocardiography can show characteristics findings, further diagnostic modalities
      are required for diagnosis. The gold standard of the diagnosis is presence of the
      amyloid in a tissue biopsy specimen. We present here a case of AL amyloidosis
      with presenting rapid progressive heart failure. Despite improvements in
      diagnostic and therapeutic modalities, diagnosis is difficult and prognosis is
      still poor in patients with cardiac involvement as in the present case. 

PMID- 23868675
TI  - Electrochemical and magnetic properties of a surface-grafted novel endohedral
      metallofullerene derivative.
AB  - A novel endohedral metallofullerene (EMF) has been designed and synthesised for
      its grafting on gold. The functionalization of the substrate resulted in a
      multifunctional surface displaying the properties of the EMF in solution. 

PMID- 23868676
TI  - Controlled synthesis of Bi2S3/ZnS microspheres by an in situ ion-exchange process
      with enhanced visible light photocatalytic activity.
AB  - A novel Bi2S3/ZnS heterostructure has been synthesized through an in situ cation
      exchange method between ZnS and bismuth(III) chloride. The obtained samples were
      characterized by multiform techniques, such as X-ray diffraction, field emission
      scanning electron microscopy, high-resolution transmission microscopy, UV-visible
      diffuse-reflectance spectroscopy, and photoluminescence spectra. The
      photocatalytic activities of the obtained photocatalysts were measured by the
      degradation of rhodamine B (RhB) and refractory oxytetracycline (OTC) under
      visible-light irradiation (lambda >= 400 nm). The as-prepared Bi2S3/ZnS
      photocatalysts exhibit wide absorption in the visible-light region and display
      superior visible-light-driven photocatalytic activities in degradation of RhB and
      OTC compared with pristine ZnS microspheres and Bi2S3 nanorods. The dramatic
      enhancement in the visible light photocatalytic performance of the Bi2S3/ZnS
      composites could be attributed to the effective electron-hole separations at the
      interfaces of the two semiconductors, which facilitate the transfer of the
      photoinduced carriers. The present study provides helpful insight into the design
      of novel and highly efficient sulfate heterostructure photocatalysts.

PMID- 23868677
TI  - Intra-abdominal pressure during swimming.
AB  - The present study aimed to determine the intra-abdominal pressure during front
      crawl swimming at different velocities in competitive swimmers and to clarify the
      relationships between stroke indices and changes in intra-abdominal pressure. The
      subjects were 7 highly trained competitive collegiate male swimmers. Intra
      abdominal pressure was measured during front crawl swimming at 1.0, 1.2 and 1.4 m
      . s(-1) and during the Valsalva maneuver. Intra-abdominal pressure was taken as
      the difference between minimum and maximum values, and the mean of 6 stable front
      crawl stroke cycles was used. Stroke rate and stroke length were also measured as
      stroke indices. There were significant differences in stroke rate among all
      velocities (P < 0.05). However, there was no significant difference in stroke
      length by velocity. Significant within-subject correlations between intra
      abdominal pressure and stroke rate or stroke length (P < 0.01) were observed,
      although there were no significant correlations between intra-abdominal pressure
      and stroke indices when controlling for swimming velocity. These findings do not
      appear to support the effectiveness of trunk training performed by competitive
      swimmers aimed at increasing intra-abdominal pressure.

PMID- 23868678
TI  - ACTN3 R577X genotype is associated with sprinting in elite Japanese athletes.
AB  - The ACTN3 R577X genotype has been found to associate with sprint/power phenotypes
      in all elite athlete cohorts investigated. This association has not been
      extensively studied in elite Asian athletes. The present study was undertaken to
      investigate the association between the ACTN3 R577X genotype and elite Japanese
      track and field athlete status. 299 elite Japanese track and field athletes (134
      sprint/power athletes; 165 endurance/middle-power athletes) and 649 Japanese
      controls were genotyped for the ACTN3 R577X polymorphism. All athletes were of
      national or international level. Sprint/power athletes showed a higher frequency
      of RR + RX genotype than controls (111/134 [82.8%] vs. 478/649 [73.7%], P = 0.025
      under the R-dominant model), while there was no significant difference between
      endurance/middle-power athletes and controls (126/165 [76.4%] vs. 478/649
      [73.7%], P = 0.48 under the R-dominant model). Sprinters with the RR + RX
      genotype had significantly faster personal best times for the 100 m than those
      with XX genotype (10.42 +/- 0.05 s vs. 10.64 +/- 0.09 s, P = 0.042); no such
      association was found in the 400 m sprinters (47.02 +/- 0.36 s vs. 47.56 +/- 0.99
      s, P = 0.62). ACTN3 R577X genotype is associated with sprint/power performance in
      elite Japanese track and field athletes, especially short sprint performance.

PMID- 23868679
TI  - Effects of different physical exercises on leptin concentration in obese
      adolescents.
AB  - In order to compare the effects of leisure physical activity (LPA), aerobic
      training (AT) and aerobic plus resistance training (AT + RT) as part of a 6-month
      interdisciplinary therapy in body composition, insulin resistance and leptin
      concentrations in obese adolescents, 72 volunteers (n = 24 in each group) ages 15
      19 years were evaluated. Delta (Delta) body mass (kg) and Delta BMI (kg/m(2)) was
      different between AT and LPA groups and in AT + RT group compared to both LPA and
      AT groups; Delta body fat mass (kg and %) was different only in AT + RT group
      compared to both LPA and AT; Delta body lean mass (%) was different only in AT +
      RT group; Delta body lean mass (kg) was negative only in AT and positive and
      different from AT in AT + RT group; DeltaHOMA-IR did not differ among groups;
      Delta leptin (ng/ml) was negative and different from LPA for both AT and AT + RT
      groups. In conclusion, both AT and AT + RT promoted a reduction on leptin levels,
      however, the adolescents subjected to AT + RT presented better results in body
      composition than the AT group. These results highlight the importance of
      associating aerobic and resistance training with nutritional and psychological
      approaches in the treatment of obese adolescents.

PMID- 23868680
TI  - Knee and hip joint biomechanics are gender-specific in runners with high running
      mileage.
AB  - Female runners are reported to be more prone to develop specific knee joint
      injuries than males. It has been suggested that increased frontal plane joint
      loading might be related to the incidence of these knee injuries in running. The
      purpose of this study was to evaluate if frontal plane knee and hip joint
      kinematics and kinetics are gender-specific in runners with high mileage. 3D
      kinematics and kinetics were recorded from 16 female and 16 male runners at a
      speed of 3 m/s, 4 m/s, and 5 m/s. Frontal plane joint angles and joint moments
      were ascertained and compared between genders among speed conditions. Across all
      speed conditions, females showed increased hip adduction and reduced knee
      adduction angles compared to males (p < 0.003). The initial peak in the hip
      adduction moment was enhanced in females (p = 0.003). Additionally, the hip
      adduction impulse showed a trend towards an increase in females at slow running
      speed (p = 0.07). Hip and knee frontal plane joint kinematics are gender
      specific. In addition, there are indications that frontal plane joint loading is
      increased in female runners. Future research should focus on the relationship of
      these observations regarding overuse running injuries.

PMID- 23868681
TI  - Recovery of damaged skeletal muscle in mdx mice through low-intensity endurance
      exercise.
AB  - The lack of dystrophin in mdx mice leads to cycles of muscle degeneration and
      regeneration processes. Various strategies have been proposed in order to reduce
      the muscle-wasting component of muscular dystrophy, including implementation of
      an exercise programme. The aim of this study was to examine how low-intensity
      endurance exercise affects the degeneration-regeneration process in dystrophic
      muscle of male mdx mice. Mice were subjected to low-intensity endurance exercise
      by running on a motorized Rota-Rod for 5 days/week for 6 weeks.
      Histomorphological analysis showed a significant reduction of measured
      inflammatory-necrotic areas in both gastrocnemius and quadriceps muscle of
      exercised mdx mice as compared to matched sedentary mdx mice. The degenerative
      regenerative process was also evaluated by examining the protein levels of
      connexin 39 (Cx39), a specific gene expressed in injured muscles. Cx39 was not
      detected in sedentary wild type mice, whereas it was found markedly increased in
      sedentary mdx mice, revealing active muscle degeneration-regeneration process.
      These Cx39 protein levels were significantly reduced in muscles of mdx mice
      exercised for 30 and 40 days, revealing together with histomorphological analysis
      a strong reduction of degeneration process in mice subjected to low-intensity
      endurance exercise. Muscles of exercised mdx mice did not show significant
      changes in force and fatigue resistance as compared to sedentary mdx mice.
      Overall in this study we found that specific low-intensity endurance exercise
      induces a beneficial effect probably by reducing the degeneration of dystrophic
      muscle. 

PMID- 23868682
TI  - Variability of serum markers of erythropoiesis during 6 days of racing in highly
      trained cyclists.
AB  - The athlete biological passport for the fight against doping is currently based
      on longitudinal monitoring for abnormal changes in cellular blood parameters.
      Serum parameters related to altered erythropoiesis could be considered for
      inclusion in the passport. The aim of this study was to quantify the changes in
      such parameters in athletes during a period of intense exercise.12 highly trained
      cyclists tapered for 3 days before 6 days of simulated intense stage racing.
      Morning and afternoon blood samples were taken on most days and analysed for
      total protein, albumin, soluble transferrin receptor and ferritin concentrations.
      Plasma volume was determined via total haemoglobin mass measured by carbon
      monoxide rebreathing. Percent changes in means from baseline and percent standard
      errors of measurement (analytical error plus intra-athlete variation) on each
      measurement occasion were estimated with mixed linear modelling of log
      transformed measures. Means of all variables changed substantially in the days
      following the onset of racing, ranging from -13% (haemoglobin concentration) to
      +27% (ferritin). After the second day, errors of measurement were generally twice
      those at baseline. Plasma variables were affected by heavy exercise, either
      because of changes in plasma volume (total protein, albumin, haemoglobin), acute
      phase/inflammatory reactions (ferritin) or both (soluble transferrin receptor).
      These effects need to be taken into consideration when integrating a plasma
      parameter into the biological passport model for athletes.

PMID- 23868683
TI  - Fluid replacement strategy during a 27-Km trail run in hot and humid conditions.
AB  - We evaluated the effects of the fluid replacement strategy on core temperature,
      heart rate and urine osmolality during a 27-km trail run in tropical climate. 20
      well-trained runners completed a 27-km trail race in tropical conditions. They
      were acclimatized to these conditions. Heart rate was monitored every 5 s, while
      core temperature and perceived thermal and comfort sensations were recorded
      before, at the 11(th) km, and just after the end of the race. Water intake, urine
      osmolality and body mass were measured before and after the race. Core
      temperature and the scores of perceived thermal and comfort sensations were
      significantly higher at the 11(th) km and at the end of the race compared to
      before the race, but not at the 11(th) km compared to the end of the race
      [corrected]. No participant exhibited dehydration as assessed by urine
      osmolality. The less the trail runners weighed, the greater the heat retention
      was. The less hot they felt at the end of the race, the more they lost water, and
      the better the performance was. The fastest runners were able to tolerate a
      greater variation in core temperature between the beginning and the end of the
      trail race with lower water intake.

PMID- 23868684
TI  - The variability of high intensity exercise tests in -pre-pubertal boys.
AB  - The aim of the study was to determine the variability of different performance
      tests during high intensity exercise in active, untrained pre- and early pubertal
      boys. Participants were habituated to the Wingate anaerobic test (WAnT), force
      velocity test (FVt), standing broad jump (SBJ), vertical jump test (VJT) and 40 m
      sprint test and repeated these procedures once a week for a period of 6 weeks. 54
      active, but untrained, prepubertal boys (mean+/-SD) (age 12.1+/-0.3 years,
      stature 1.55+/-0.06 m, and body mass 47.9+/-10.2 kg) were recruited. After Wk2,
      the variability of short-term power output was low in prepubertal boys, for
      example, for WAnT-determined peak power (CV%=3.4%; ICC=0.982; mean bias+/-random
      error=10+/-50 W) and this trend was also evident for tests of athletic
      performance (for example, the 40 m sprint test, CV%=1.3%; ICC=0.990; mean bias+/
      random error=0.01+/-0.59 s). Variability was reduced further at Wk6 for all high
      intensity exercise tests. The findings of the current study indicate that tests
      of short-term power output and athletic performance are reliable from a single
      measurement given an appropriate period of habituation and strict standardisation
      of test procedures in pre- and early pubertal boys. 

PMID- 23868685
TI  - Effect of short-term maximal voluntary co-contraction training on neuromuscular
      function.
AB  - The present study aimed to examine the effect of short-term training utilizing
      voluntary co-contraction with maximal efforts. 23 healthy young men (training
      group: TG, n = 13; control group: CG, n = 10) participated in this study. TG
      conducted a 4-week training program (3 days/week), which consisted of 4 s
      simultaneous maximal voluntary contractions of elbow flexors and extensors at 90
      degrees  of the elbow joint, followed by 4 s muscle relaxation (10
      repetitions/set, 5 sets/day). Before and after the intervention, maximal
      voluntary isometric and isokinetic torques and the muscle thicknesses of the
      elbow flexors and extensors were determined. The electromyograms (EMGs) of the 2
      muscle groups during isometric maximal voluntary contraction (MVC) were also
      recorded. After the intervention, CG did not show any significant changes in all
      measured variables. In TG, significant increases were found in the agonist EMG
      activities during MVC, and maximal isometric and isokinetic torques of the elbow
      flexors and extensors, without significant changes in the muscle thicknesses and
      involuntary coactivation levels during MVC. The current results indicate that the
      training mode with maximal voluntary co-contraction is effective for improving
      the force-generating capabilities of the exercising muscles, without any
      increases in the level of involuntary coactivation during MVC.

PMID- 23868686
TI  - Variability in heart rate recovery measurements over 1 year in healthy, middle
      aged adults.
AB  - This study assessed the longer-term (12-month) variability in post-exercise heart
      rate recovery following a submaximal exercise test. Longitudinal data was
      analysed for 97 healthy middle-aged adults (74 male, 23 female) from 2 occasions,
      12 months apart. Participants were retrospectively selected if they had stable
      physical activity habits, submaximal treadmill fitness and anthropometric
      measurements between the 2 assessment visits. A submaximal Bruce treadmill test
      was performed to at least 85% age-predicted maximum heart rate. Absolute heart
      rate and Delta heart rate recovery (change from peak exercise heart rate) were
      recorded for 1 and 2 min post-exercise in an immediate supine position. Heart
      rate recovery at both time-points was shown to be reliable with intra-class
      correlation coefficient values >= 0.714. Absolute heart rate 1-min post-exercise
      showed the strongest agreement between repeat tests (r = 0.867, P < 0.001). Lower
      coefficient of variation (<= 10.2%) and narrower limits of agreement were found
      for actual heart rate values rather than Delta heart rate recovery, and for 1-min
      rather than 2-min post-exercise recovery time points. Log-transformed values
      generated better variability with acceptable coefficient of variation for all
      measures (2.2-10%). Overall, 1 min post-exercise heart rate recovery data had
      least variability over the 12-month period in apparently healthy middle-aged
      adults.

PMID- 23868687
TI  - Nonfunctional overreaching leads to inflammation and myostatin upregulation in
      swiss mice.
AB  - The aims of the this study were a) to verify whether the performance decrease
      induced by nonfunctional overreaching (NFOR) is linked to high concentrations of
      cytokines in serum, skeletal muscles and liver; b) to verify muscle myostatin
      adaptation to NFOR; c) to verify the effects of chronic glucose supplementation
      on the parameters mentioned above. Mice were divided into control (C), trained
      (TR), overtrained (OTR) and supplemented overtrained (OTR + S). The incremental
      load test (ILT) and exhaustive test (ET) were used to measure performances before
      and after exercise protocols. 24 h after ET, muscles and liver were removed and
      stored at -80 degrees C for subsequent measurements. Total blood was collected
      from decapitation for subsequent determination of cytokine concentrations.
      Generally, OTR and OTR + S presented higher contents of IL-6, TNF-alpha, GLUT-4
      and myostatin in muscle samples compared to C and TR. Glucose supplementation
      attenuated the high contents of IL-6, TNF-alpha and IL-15 in liver, and of IL-6
      in serum. In summary, NFOR led to low-grade chronic inflammation and myostatin
      upregulation.

PMID- 23868688
TI  - Motion characteristics of youth women soccer matches: female athletes in motion
      (FAiM) study.
AB  - This study determined the locomotor characteristics for youth female soccer
      matches. 89 female soccer players (U-15-U-17) were assessed during a youth
      national championship or a talent identification camp using a Global Positioning
      System. Positional and age-group comparisons of locomotor characteristics were
      made for complete games, each half, differences between halves as well as sprint
      profiles using an ANCOVA adjusting for the differences in game or half durations,
      respectively. Midfielders covered greater distances (8 449 +/- 170 m) than
      defenders (7 779 +/- 114 m), mostly from more low- (2 553 +/- 99 m vs. 2 151 +/-
      66 m) and moderate-speed running (1 389 +/- 78 m vs. 1 142 +/- 52 m). Forwards
      had more sprint distances (275 +/- 42 m), sprints (15 +/- 2) and greater maximum
      speed (26.7 +/- 0.6 km . h(-1)) than midfielders (131 +/- 24 m, 8 +/- 1, 24.7 +/-
      0.4 km . h(-1), respectively). There was a tendency for increased distances
      within most velocity bands, workrate and sprints with increasing age. There was a
      greater increase in walking and jogging between the first and second half for
      forwards than defenders and midfielders. Youth female soccer players covered 6
      500-9 000 m during matches with positional distinctions that are comparable to
      elite-standard women. These data provide novel insight into the physical demands
      of female youth soccer and should be used to establish appropriate age-group and
      positional strategies for training and development.

PMID- 23868689
TI  - Enhancing gold recovery from electronic waste via lixiviant metabolic engineering
      in Chromobacterium violaceum.
AB  - Conventional leaching (extraction) methods for gold recovery from electronic
      waste involve the use of strong acids and pose considerable threat to the
      environment. The alternative use of bioleaching microbes for gold recovery is non
      pollutive and relies on the secretion of a lixiviant or (bio)chemical such as
      cyanide for extraction of gold from electronic waste. However, widespread
      industrial use of bioleaching microbes has been constrained by the limited
      cyanogenic capabilities of lixiviant-producing microorganisms such as
      Chromobacterium violaceum. Here we show the construction of a metabolically
      engineered strain of Chromobacterium violaceum that produces more (70%) cyanide
      lixiviant and recovers more than twice as much gold from electronic waste
      compared to wild-type bacteria. Comparative proteome analyses suggested the
      possibility of further enhancement in cyanogenesis through subsequent metabolic
      engineering. Our results demonstrated the utility of lixiviant metabolic
      engineering in the construction of enhanced bioleaching microbes for the
      bioleaching of precious metals from electronic waste. 

PMID- 23868690
TI  - Optimization of retinotopy constrained source estimation constrained by prior.
AB  - Studying how the timing and amplitude of visual evoked responses (VERs) vary
      between visual areas is important for understanding visual processing but is
      complicated by difficulties in reliably estimating VERs in individual visual
      areas using noninvasive brain measurements. Retinotopy constrained source
      estimation (RCSE) addresses this challenge by using multiple, retinotopically
      mapped stimulus locations to simultaneously constrain estimates of VERs in visual
      areas V1, V2, and V3, taking advantage of the spatial precision of fMRI
      retinotopy and the temporal resolution of magnetoencephalography (MEG) or
      electroencephalography (EEG). Nonlinear optimization of dipole locations, guided
      by a group-constrained RCSE solution as a prior, improved the robustness of RCSE.
      This approach facilitated the analysis of differences in timing and amplitude of
      VERs between V1, V2, and V3, elicited by stimuli with varying luminance contrast
      in a sample of eight adult humans. The V1 peak response was 37% larger than that
      of V2 and 74% larger than that of V3, and also ~10-20 ms earlier. Normalized
      contrast response functions were nearly identical for the three areas. Results
      without dipole optimization, or with other nonlinear methods not constrained by
      prior estimates were similar but suffered from greater between-subject
      variability. The increased reliability of estimates offered by this approach may
      be particularly valuable when using a smaller number of stimulus locations,
      enabling a greater variety of stimulus and task manipulations.

PMID- 23868692
TI  - A comparison study of methods for measuring retention in HIV medical care.
AB  - The purpose of this study was to compare multiple measures of retention in HIV
      medical care by determining their ability to predict viral suppression. Patients
      who sought care between 2003 and 2011 were eligible. Visit constancy, gaps-in
      care, and HRSA measure were the measures compared. Multiple logistic regressions
      and area under the curve statistics were employed to determine which measure most
      accurately discerned between patients with or without viral suppression. There
      were 850 patients included in the study. The mean follow-up time among the cohort
      was 5.6 years and less than half were consistently retained in care. All three
      measures had similar area under the curves, but only visit constancy and gaps in
      care were significantly associated with viral suppression. Retention in care
      should be defined consistently across studies and interventions should be set in
      place to increase the number of optimal retainers.

PMID- 23868691
TI  - Situational, partner, and contextual factors associated with level of risk at
      most recent intercourse among Black men who have sex with men.
AB  - African American men who have sex with men (MSM) in the United States bear a
      disproportionate burden of HIV infection and disease incidence. 178 Black MSM
      provided detailed situational information concerning their most recent act of
      anal intercourse (AI) with a male partner including condom use, partner
      characteristics, serostatus disclosure, and substance use. Participants completed
      scales assessing AIDS-related as well as broader contextual domains. Most recent
      AI acts occurred with same-race partners outside of main relationships. Over one
      third of AI acts were unprotected, and almost half of the unprotected acts were
      not between known HIV-concordant partners. Nearly half of men reported substance
      use before sex. In a multiple regression analysis, unprotected AI with a partner
      not known to be concordant was predicted by low risk reduction intentions and
      indicators of a casual relationship. The findings highlight issues and partner
      contexts associated with risk for contracting HIV infection among Black MSM. 

PMID- 23868693
TI  - Micropatterned photodegradable hydrogels for the sorting of microbeads and cells.

PMID- 23868694
TI  - Systematic review of blood biomarkers in cystic fibrosis pulmonary exacerbations.
AB  - BACKGROUND: Biomarkers reflective of disease activity in cystic fibrosis (CF)
      have the potential to improve patient care, particularly during CF pulmonary
      exacerbations (CFPEs). Although blood-based biomarkers have been studied in CFPE
      for nearly 3 decades, none have been integrated into routine clinical practice.
      To facilitate progress in this area, we performed a systematic review evaluating
      blood-based biomarkers during CFPE. METHODS: MEDLINE, EMBASE, and CENTRAL were
      searched to identify relevant studies published from January 1995 to August 2012.
      We included all full-text studies examining systemic (blood-based) biomarkers to
      aid in the diagnosis of CFPE, predict outcomes of CFPE, and/or monitor the
      response to CFPE treatment. RESULTS: Seventy-eight unique blood-based biomarkers
      have been studied to date, mainly inflammatory cytokines, acute phase reactants,
      and markers of oxidative stress. C-reactive protein (CRP) consistently correlated
      with disease activity, with a statistically significant increase from stable to
      exacerbation state in five of six studies, and changes in response to CFPE
      treatment, with a statistically significant decrease from the beginning to the
      end of CFPE treatment in 18 of 20 studies. Other promising biomarkers of CFPE
      disease activity include neutrophil elastase antiproteinase complex, IL-6,
      myeloperoxidase (MPO), lactoferrin, and calprotectin. CONCLUSIONS: Although there
      are several blood-based biomarkers with evidence for application within the CFPE
      setting, CRP has been the most widely studied biomarker demonstrating the
      potential for clinical usefulness. Further validation studies and clinical trials
      are required to determine whether blood-based biomarkers can be used to
      ultimately improve health outcomes in the setting of a CFPE.

PMID- 23868695
TI  - Treatment outcome of relapsed/refractory primary central nervous system diffuse
      large B-cell lymphoma: a single-center experience of autologous stem cell
      transplantation.
AB  - No salvage treatment strategy has been established for relapsed or refractory
      primary central nervous system lymphoma (PCNSL). We compared treatment outcomes
      of patients who underwent salvage chemotherapy with or without autologous stem
      cell transplantation (ASCT). We retrospectively analyzed PCNSL patients who were
      histologically diagnosed with diffuse large B-cell lymphoma. All patients
      relapsed after high-dose methotrexate (MTX)-based chemotherapy, or were
      refractory to high-dose MTX. Patients were treated with salvage chemotherapy,
      such as ICE/D (ifosfamide, carboplatin, etoposide, and dexamethasone) or high
      dose MTX. High-dose chemotherapy containing thiotepa and busulfan followed by
      ASCT was performed if patients were eligible for ASCT after salvage treatment.
      Forty-five patients (35 relapsed and 10 refractory) received ICE/D or high-dose
      MTX. Despite the important difference that ICE/D was used predominantly for early
      relapsed or refractory patients, the two salvage treatments produced similar
      overall response rates [84.4 % (38/45) for ICE/D and 81.3 % (13/16) for high-dose
      MTX re-treatment]. Eighteen patients underwent ASCT, whereas 27 patients received
      salvage chemotherapy alone. The median progression-free survival of patients who
      underwent ASCT (19.5 months) was significantly better than that of patients who
      did not receive ASCT (6.7 months, P = 0.023). Multivariate analysis showed that
      refractoriness to initial treatment and no ASCT were significantly associated
      with poor survival outcome. Our study suggested that the combination of
      ifosfamide, carboplatin, etoposide, and dexamethasone may represent a feasible
      salvage treatment option for relapsed or refractory PCNSL, and that high-dose
      chemotherapy containing thiotepa and busulfan followed by ASCT may be effective
      for patients with a favorable toxicity profile. 

PMID- 23868696
TI  - Deaf readers' response to syntactic complexity: evidence from self-paced reading.
AB  - This study was designed to determine the feasibility of using self-paced reading
      methods to study deaf readers and to assess how deaf readers respond to two
      syntactic manipulations. Three groups of participants read the test sentences:
      deaf readers, hearing monolingual English readers, and hearing bilingual readers
      whose second language was English. In Experiment 1, the participants read
      sentences containing subject-relative or object-relative clauses. The test
      sentences contained semantic information that would influence online processing
      outcomes (Traxler, Morris, & Seely Journal of Memory and Language 47: 69-90,
      2002; Traxler, Williams, Blozis, & Morris Journal of Memory and Language 53: 204
      224, 2005). All of the participant groups had greater difficulty processing
      sentences containing object-relative clauses. This difficulty was reduced when
      helpful semantic cues were present. In Experiment 2, participants read active
      voice and passive-voice sentences. The sentences were processed similarly by all
      three groups. Comprehension accuracy was higher in hearing readers than in deaf
      readers. Within deaf readers, native signers read the sentences faster and
      comprehended them to a higher degree than did nonnative signers. These results
      indicate that self-paced reading is a useful method for studying sentence
      interpretation among deaf readers. 

PMID- 23868697
TI  - The effect of newly trained verbal and nonverbal labels for the cues in
      probabilistic category learning.
AB  - Learning in a well-established paradigm of probabilistic category learning, the
      weather prediction task, has been assumed to be mediated by a variety of
      strategies reflecting explicit learning processes, such as hypothesis testing,
      when it is administered to young healthy participants. Higher categorization
      accuracy has been observed in the task when explicit processes are facilitated.
      We hypothesized that furnishing verbal labels for the cues would boost the
      formation, testing, and application of verbal rules, leading to higher
      categorization accuracy. We manipulated the availability of cue names by training
      separate groups of participants for three consecutive days to associate hard-to
      name artificial auditory cues to pseudowords or to hard-to-name ideograms, or to
      associate stimulus intensity with colors; a fourth group remained unexposed to
      the cues. Verbal labels, cue individuation, and exposure to the stimulus set each
      had an additive effect on categorization performance in a subsequent 200-trial
      session of the weather prediction task using these auditory cues. This study
      suggests that cue nameability, when controlled for cue individuation and cue
      familiarity, has an effect on hypothesis-testing processes underlying category
      learning. 

PMID- 23868698
TI  - Homosexuality via canalized sexual development: a testing protocol for a new
      epigenetic model.
AB  - We recently synthesized and reinterpreted published studies to advance an
      epigenetic model for the development of homosexuality (HS). The model is based on
      epigenetic marks laid down in response to the XX vs. XY karyotype in embryonic
      stem cells. These marks boost sensitivity to testosterone in XY fetuses and lower
      it in XX fetuses, thereby canalizing sexual development. Our model predicts that
      a subset of these canalizing epigenetic marks stochastically carry over across
      generations and lead to mosaicism for sexual development in opposite-sex
      offspring--the homosexual phenotype being one such outcome. Here, we begin by
      outlining why HS has been under-appreciated as a commonplace phenomenon in
      nature, and how this trend is currently being reversed in the field of
      neurobiology. We next briefly describe our epigenetic model of HS, develop a set
      of predictions, and describe how epigenetic profiles of human stem cells can
      provide for a strong test of the model.

PMID- 23868699
TI  - [Living situation of mentally disabled people with dementia in institutions for
      the disabled: results of a questionnaire in Lower Saxony and Bremen].
AB  - No empirical data about the topic "Mental Disability and Dementia" in Germany
      exist. The aim of this survey was to obtain current data about mentally disabled
      people with dementia. Therefore, the following questions need to be clarified:
      how many mentally disabled people are affected with dementia, which difficulties
      occur regarding the diagnosis of dementia and what challenges have to be solved
      in upcoming years. In all, 45 organisations for the mentally disabled took part
      in the survey, showing that dementia amongst people with mental disabilities
      appeared largely starting at the age of 50. Standardized diagnostics are seldom
      used by these organisations. Instead, observation of behaviour by care attendants
      plays a central role, due to the fact that speaking and introspection are not
      possible for a majority of the patients. In general, institutions for people with
      mental disabilities do not have specific offers for people with dementia,
      occasionally there are offers regarding their living situation and free time
      activities. 

PMID- 23868700
TI  - Aging-mechanisms, models, and translation.

PMID- 23868701
TI  - Treatment of neonatal abstinence syndrome in preterm and term infants.
AB  - OBJECTIVE: Neonatal abstinence syndrome (NAS) is treated with a variety of drug
      preparations. With the optional treatment of NAS with chloral hydrate,
      phenobarbital or morphine the cumulative drug consumption of the mentioned drugs,
      the length of hospital stay and treatment duration was evaluated in preterm and
      term neonates. METHODS: Retrospective, uncontrolled study which evaluates
      different therapies of neonatal abstinence syndrome (NAS) in preterm and term
      neonates. RESULTS: During the past 16 years data were obtained from medical
      records of 51 neonates with NAS; 9 preterm and 35 term neonates were evaluated
      and 7 were excluded because of incomplete data sets. 31 (72.1%) received a
      pharmacological treatment (6 preterm and 25 term neonates). Treatment started at
      4.3 [3.3-5.3] d. Mean duration of treatment was 11.7 [6.6-16.7] d. In our study
      chloral hydrate (ch) and phenobarbital (pb) were first line medication escalated
      by the morphine (mp) solution. Mean cumulative dosage of ch was 643.5 [260.3-1
      026.7] mg, of pb 53.2 [19.7-86.8] mg and of mp 4.22 [0-8.99] mg. CONCLUSION: Our
      study group showed similar treatment duration and length of hospital stay
      compared to other studies. The cumulative dose of mp was lower compared to most
      studies. This benefit resulted at the expense of a further medication with pb and
      ch. However, 6 of 9 preterm neonates needed significantly less pharmacological
      therapy compared to term neonates indicating less susceptibility of immature
      brain to abstinence of maternalo-pioids.

PMID- 23868702
TI  - A nanoporous PdCo alloy as a highly active electrocatalyst for the oxygen
      reduction reaction and formic acid electrooxidation.
AB  - A nanoporous (NP) PdCo alloy with uniform structure size and controllable
      bimetallic ratio was fabricated simply by one-step mild dealloying of a PdCoAl
      precursor alloy. The as-made alloy consists of a nanoscaled bicontinuous network
      skeleton with interconnected hollow channels that extend in all three dimensions.
      With a narrow ligament size distribution around 5 nm, the NP PdCo alloy exhibits
      much higher electrocatalytic activity towards the oxygen-reduction reaction (ORR)
      with enhanced specific and mass activities relative to NP Pd and commercial Pt/C
      catalysts. A long-term stability test demonstrated that NP PdCo has comparable
      catalytic durability with less loss of ORR activity and electrochemical surface
      area than Pt/C. The NP PdCo alloy also shows dramatically enhanced catalytic
      activity towards formic acid electrooxidation relative to NP Pd and Pd/C
      catalysts. The as-made NP PdCo holds great application potential as a promising
      cathode as well as an anode electrocatalyst in fuel cells with the advantages of
      superior catalytic performance and easy preparation.

PMID- 23868703
TI  - Correlation between Al(3+) -induced thermal stability and inhibition of
      fibrillation of N-terminal domain of the hydrogenase maturation factor.
AB  - Fibrillation can be induced in proteins by altering solvent conditions.
      Stabilization of the protofibrillar structure arrests formation of longer fibers.
      Thermal stability and fibrillation of N-terminal domain of the hydrogenase
      maturation factor (HypF-N) were studied in the presence of a series of metal
      ions. Only Al(3+) was able to reverse the thermal denaturation of HypF-N upon
      heating. On being exposed to denaturing conditions, the native protein formed
      fibrillar structure under moderately denaturing conditions, whereas in the
      presence of Al(3+) , the protein was found to retain its native conformation.
      Under strongly denaturing conditions, only Al(3+) was able to stabilize the
      protein in the fibrillar state. Spectrofluorimetric analysis revealed that Al(3+)
      alone was able to stabilize the partially unfolded intermediate state of HypF-N.
      Based on the similarity in observations, we propose a link between reversal of
      thermal instability of HypF-N and its ability to form an intermediate structure
      in the presence of Al(3+) . Al(3+) stabilizes the partially unfolded state in the
      N<->I<->U equilibrium so that upon heating, the three-dimensional structure of
      the protein is not lost completely. Kinetic analysis confirmed that Al(3+)
      interacts with an early structure on the aggregation landscape and delays
      fibrillation. Under mildly denaturing state, HypF-N is able to recover its native
      conformation in the presence of Al(3+) and under strongly denaturing conditions,
      the protein does not acquire a completely disordered structure. Instead, it forms
      an ordered beta-sheet-rich structure.

PMID- 23868704
TI  - An unusual case of risperidone instability in a fatality presenting an analytical
      and interpretative challenge.
AB  - This paper describes the detection and characterization of unusual
      metabolite/breakdown products of the anti-psychotic drug risperidone in post
      mortem blood and urine as part of a toxicological investigation into an
      unexpected death of a male suffering from paranoid schizophrenia prescribed
      risperidone and previously paroxetine. Compounds detected in the post-mortem
      blood and urine specimens were shown to be benzisoxazole ring scission products
      of risperidone and a hydroxy metabolite. These compounds are never routinely
      detected in blood and urine but can be present in mammalian faeces indicating
      that gut bacteria could be responsible for their formation. In this case,
      evidence for this process was demonstrated by the controlled in vitro stability
      study of risperidone spiked into the case blood and urine leading to the
      hypothesis that the post-mortem blood and urine samples analyzed could have
      contained bacteria with the ability to breakdown risperidone and its metabolite
      in this way. This finding is very unusual and has not been encountered before in
      any previous risperidone cases investigated by the authors, or widely reported in
      the post-mortem toxicological literature. However, a recently published paper has
      supported these findings in blood. As a result of this work, it was shown that
      the deceased had taken risperidone prior to death, even in the absence of any
      risperidone or its hydroxy metabolite(s) in the blood and urine. Given that
      risperidone has been reported to interact with paroxetine, the ingestion of
      risperidone could have been a factor that contributed to the death.

PMID- 23868705
TI  - Potentially functional genetic variants in microRNA processing genes and risk of
      HBV-related hepatocellular carcinoma.
AB  - Genetic variations in miRNA processing genes may affect the biogenesis of miRNA,
      hence risk of HBV infection and hepatocellular carcinoma (HCC) development. In
      the present study, we hypothesized that potentially functional polymorphisms in
      3'-untranslated region (UTR) of miRNA processing genes might contribute to
      susceptibility of HBV infection and HCC development. To test the hypothesis, we
      genotyped three selected SNPs (rs1057035 in DICER1, rs3803012 in RAN, and
      rs10773771 in PIWIL1) in a case-control study of 1300 HBV-positive HCC cancer
      cases, 1344 HBV persistent carriers, and 1344 HBV natural clearance subjects in
      Chinese. We observed that DICER1 rs1057035 CT/CC variant genotypes were
      associated with a significant decreased risk of HCC (adjusted OR = 0.79, 95% CI =
      0.64-0.96) compared with wild-type TT and RAN rs3803012 AG/GG variant genotypes
      increased the risk of HBV persistent infection compared with AA genotype
      (adjusted OR = 1.35, 95% CI = 1.03-1.77). However, PIWIL1 rs10773771 CT/CC
      variant genotypes were associated with an approaching decreased risk of HCC
      (adjusted OR = 0.86, 95% CI = 0.73-1.01) and similar with RAN rs3803012 AG/GG
      (adjusted OR = 0.80, 95% CI = 0.61-1.06). Furthermore, reporter gene assays
      indicated that the three SNPs (rs1057035, rs3803012, and rs10773771) might change
      the binding ability of miRNAs to the 3'UTR of the three genes (DICER1, RAN, and
      PIWIL1), respectively. These findings indicated that DICER1 rs1057035, RAN
      rs3803012, and PIWIL1 rs10773771 might contribute to the risk of HBV-related HCC.

PMID- 23868706
TI  - [Can long-term treatment with antipsychotic drugs lead to structural brain
      damage? Pro].

PMID- 23868707
TI  - Ultra-performance liquid chromatography MS/MS method for the determination of
      parabens in compost from sewage sludge: comparison of the efficiency of two
      extraction techniques.
AB  - The efficiency of two extraction techniques--ultrasound-assisted extraction and
      pressurized liquid extraction--are compared and evaluated in the determination of
      parabens in compost samples. The extraction parameters for each technique were
      accurately optimized. The selected compounds were detected and quantified using
      ultra-performance LC MS/MS, operating in negative ESI and in SRM mode. The
      analytes were separated in less than 5 min. Ethylparaben (ring-(13)C6 labeled)
      was used as an internal standard. Two selective, sensitive, and accurate
      analytical methods were developed and validated. The LODs of the methods ranged
      from 3 to 7 ng/g and the LOQs from 10 to 23 ng/g, while inter- and intraday
      variability was under 6% in all cases. The methods were validated separately by
      using matrix-matched calibration and recovery assays with spiked samples.
      Recovery rates ranged from 94.0 to 105.0%. Compost samples were taken from
      different composting plants. Although the statistical comparison demonstrated no
      statistically significant differences between the two extraction techniques, the
      method based on pressurized liquid extraction was more sensitive than the
      ultrasound extraction based method.

PMID- 23868708
TI  - Helping youth immediately following war exposure: a randomized controlled trial
      of a school-based intervention program.
AB  - This study evaluates a school-based primary prevention intervention designed to
      promote adolescents' coping in the immediate aftermath of war exposure in
      Operation Cast Lead. Participants were 179 adolescents from two demographically
      similar schools in Ashkelon in south Israel. The intervention incorporated two
      previously proven resilience factors-mobilization of support and self-efficacy.
      In a repeated measures design, the study assessed pre- to post-test changes in
      intervention (n=94) and control (n=85) conditions among adolescents exposed to
      high or low political life events (PLE). Findings showed significant pre-test
      differences in self-efficacy and psychological symptoms between participants with
      low and high PLE. For both PLE groups, the intervention strengthened support
      mobilization and self-efficacy and reduced psychological distress and emotional
      symptoms. Findings reinforce the importance of offering appropriate evidence
      based interventions for school staff to restore security and well-being to
      adolescents in a crisis context immediately following war. Despite the apparent
      return to a school routine after war, school staff should be aware of the risk to
      youth for development of psychological symptoms and disorders, and the need for
      preventative intervention.

PMID- 23868709
TI  - Effects of tonsillectomy on sleep study parameters in adult patients with
      obstructive sleep apnea--a prospective study.
AB  - OBJECTIVE: The objective of this study is to evaluate the efficacy of
      tonsillectomy in reduction of respiratory disturbance index (RDI) and other sleep
      study parameters in patients with obstructive sleep apnea (OSA). METHODS: This
      study involves 34 adults with OSA and Friedman grade 3 or 4 tonsils. All 34
      patients were treated with tonsillectomy, as the only surgical treatment for OSA
      from 2007 to 2011. Pre- and postoperative polysomnography were performed in all
      these patients. RESULTS: Prior to tonsillectomy, 21 patients had severe, 9 had
      moderate, and 4 had mild OSA. Surgical response rate (defined as 50% or more
      reduction in apnea-hypopnea index (AHI) and a postoperative AHI of less than 20)
      was 71.4% among patients with severe OSA, 77.7% among patients with moderate, and
      75% among patients with mild. Among all the 34 patients, there was a reduction of
      24.6 (p = 0.000) in the RDI postoperatively. In our sub-analysis, we arbitrarily
      divided the patients into three groups: patients with RDI less than 30, patients
      with RDI between 30 and 60, and patients with RDI above 60. It showed that, in
      the group with RDI >60, an average reduction of RDI by 57.6 (p = 0.000) was
      achieved and was the greatest reduction in RDI. CONCLUSIONS: Tonsillectomy alone
      may be considered as an effective first line surgical procedure in the treatment
      of OSA in selected patients. Patients with Friedman grade 3 or 4 tonsils may be
      considered for tonsillectomy as the initial surgical procedure, reserving other
      upper airway procedures at a later stage if necessary.

PMID- 23868710
TI  - Serum S100A12 levels are associated with the presence and severity of obstructive
      sleep apnea syndrome in male patients.
AB  - PURPOSE: Inflammation plays a critical role in the pathogenesis of obstructive
      sleep apnea syndrome (OSAS). S100A12 is a newly identified inflammatory
      biomarker. This study aims to investigate whether serum S100A12 levels are
      associated with the presence and severity of OSAS in male patients. METHODS: A
      total of 126 male patients with OSAS and 74 controls were enrolled in this study.
      The presence and severity of OSAS was assessed by apnea-hypopnea index (AHI).
      Serum S100A12 levels were detected by enzyme-linked immunosorbent assay. RESULTS:
      Serum S100A12 levels were significantly higher in the OSAS group than in the
      control group (132.17 (range 101.86 to 174.49) ng/ml vs. 78.40 (range 58.35 to
      129.44) ng/ml, P < 0.01). Multivariate logistic regression demonstrated that
      S100A12 was the only significant and independent predictor of OSAS (odds ratio
      1.012, 95% confidence interval 1.006 to 1.017; P < 0.01). Serum S100A12 levels
      elevated with the increase in the severity of OSAS (S100A12 levels of 106.04
      (range 83.92 to 135.13) ng/ml in mild OSAS group, 133.51 (range 109.64 to 208.95)
      ng/ml in moderate OSAS group, and 173.04 (range 131.88 to 275.77) ng/ml in severe
      OSAS group; P < 0.001). Serum S100A12 levels were independently correlated with
      AHI scores (r = 0.324, P < 0.001) CONCLUSIONS: Serum S100A12 levels were
      independently associated with the presence and severity of OSAS. These findings
      suggest that serum S100A12 level could be a potential biomarker for reflecting
      the presence and severity of OSAS.

PMID- 23868711
TI  - Adaptive servoventilation vs. monoventricular assist device implantation: effects
      on quality of life and sleep in a patient with end-stage heart failure and sleep
      disordered breathing.

PMID- 23868712
TI  - Brain microdialysate, CSF and plasma pharmacokinetics of ligustrazine
      hydrochloride in rats after intranasal and intravenous administration.
AB  - The aim of this work was to investigate the pharmacokinetics of ligustrazine
      hydrochloride (LZH) in plasma, cerebrospinal fluid (CSF) and cerebral cortex
      after intranasal (10 mg/kg) or intravenous administration (10 mg/kg) in male
      Sprague-Dawley rats. Plasma, CSF and cerebral cortex microdialysates were
      collected at timed intervals for the measurement of LZH by a quick and sensitive
      HPLC-UV method. LZH entered the brain quickly following both routes of
      administration. No significant difference was observed between the AUCCSF or
      cortex /AUCplasma ratio of LZH after intranasal administration (38.4%, 17.4%) and
      that after intravenous injection (45.9%, 19.9%). The drug targeting index (DTI)
      was 0.85 and 0.91 in the CSF and cortex, respectively. In conclusion, LZH is
      rapidly absorbed into the systemic circulation following intranasal
      administration. There is no direct pathway for LZH transport from the nasal
      cavity to the brain. The rapidity and magnitude of LZH penetration into the brain
      indicate that intranasal administration of this agent is a promising alternative
      to intravenous administration.

PMID- 23868713
TI  - A cross-sectional assessment of oxidative DNA damage and muscle strength among
      elderly people living in the community.
AB  - OBJECTIVES: The mechanism by which muscle weakness leads to an increased risk of
      death remains a subject of interest. In this context, the aim of this study is to
      assess the relationship between urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and
      muscle strength, and other risk factors contributing to poor muscle strength in
      older persons. METHODS: This was a cross-sectional study in which a total of 86
      participants, both men and women, aged 65 years or above were screened for
      urinary 8-OHdG, and muscle strength as measured by handgrip strength. RESULTS:
      Handgrip strength was lower in participants who had history of acute or chronic
      disease. Urinary 8-OHdG level was negatively associated with muscle strength, and
      the association remained after adjusting for confounding factors. CONCLUSIONS:
      Urinary 8-OHdG is associated with muscle strength. These findings may be
      clinically relevant as there is a possibility of controlling oxidative DNA damage
      by healthy behaviors related to lifestyle.

PMID- 23868714
TI  - Time-varying coupling of EEG oscillations predicts excitability fluctuations in
      the primary motor cortex as reflected by motor evoked potentials amplitude: an
      EEG-TMS study.
AB  - PURPOSE: Motor evoked potentials (MEPs) elicited by a train of consecutive,
      individual transcranial magnetic stimuli demonstrate fluctuations in amplitude
      with respect to time when recorded from a relaxed muscle. The influence of time
      varying, instantaneous modifications of the electroencephalography (EEG)
      properties immediately preceding the transcranial magnetic stimulation (TMS) has
      rarely been explored. The aim of this study was to investigate the influence of
      the pre-TMS motor cortex and related areas EEG profile on time variants of the
      MEPs amplitude. METHOD: MRI-navigated TMS and multichannel TMS-compatible EEG
      devices were used. For each experimental subject, post-hoc analysis of the MEPs
      amplitude that was based on the 50th percentile of the MEPs amplitude
      distribution provided two subgroups corresponding to "high" (large amplitude) and
      "low" (small amplitude). The pre-stimulus EEG characteristics (coherence and
      spectral profile) from the motor cortex and related areas were analyzed
      separately for the "high" and "low" MEPs and were then compared. RESULTS: On the
      stimulated hemisphere, EEG coupling was observed more often in the high compared
      to the low MEP trials. Moreover, a paradigmatic pattern in which TMS was able to
      lead to significantly larger MEPs was found when the EEG of the stimulated motor
      cortex was coupled in the beta 2 band with the ipsilateral prefrontal cortex and
      in the delta band with the bilateral centro-parietal-occipital cortices.
      CONCLUSION: This data provide evidence for a statistically significant influence
      of time-varying and spatially patterned synchronization of EEG rhythms in
      determining cortical excitability, namely motor cortex excitability in response
      to TMS.

PMID- 23868715
TI  - [Risk factors for inpatient suicide].
AB  - OBJECTIVE: The study aimed to examine suicidal behaviour during in-patient care
      in a psychiatric university hospital. METHOD: Based upon a psychiatric basic
      documentation system prevalence and risk factors of in-patient suicides and
      suicide attempts were investigated (1995 - 2010). RESULTS: A total of 42 in
      patient suicides and 166 attempts were found among 16 251 patients. According to
      the multivariate logistic regression analysis the risk of suicide during
      hospitalization increases significantly for male patients, with more previous
      psychiatric hospitalizations and suicidality according to clinical impression at
      admission or suicide attempt before admission. Patients with affective or
      schizophrenic disorders were at highest risk. The following risk factors are
      associated with suicide attempt during stay: female gender, borderline
      personality disorder (F60.3), more previous psychiatric hospitalizations, shorter
      duration of disorder, earlier age of onset, suicidality according to clinical
      impression at admission or suicide attempt before admission. CONCLUSION: As
      depressive and schizophrenic patients represent the high-risk group of in-patient
      suicide, suicide prevention should be a major goal in their treatment. More
      frequent suicide risk assessment is recommended particularly before granting a
      leave or an outing.

PMID- 23868716
TI  - [The interrelation between perceived discrimination, depressiveness, and health
      related quality of life in immigrants of Turkish and Polish origin].
AB  - OBJECTIVE: Comparative study on perceived discrimination and subjective health
      status in two immigrants samples. METHODS: In a total sample consisting of 218
      immigrants of Turkish and Polish origin perceived discrimination, depressiveness
      (BDI) and health related quality of life (SF-36) were assessed. RESULTS: Turkish
      immigrants have shown higher levels of perceived discrimination and
      depressiveness as well as a lower subjective quality of life. CONCLUSIONS: The
      results indicate that Turkish immigrants have a greater mental impairment
      compared to persons with Polish migration background.

PMID- 23868717
TI  - [50 years Rodewisch theses--for the beginnings of social-psychiatric reforms in
      East Germany (GDR)].
AB  - The so-called Rodewisch Theses of 1963 demonstrate East German psychiatry's
      attempts to implement social-psychiatric reforms. To mark their 50th anniversary,
      this article analyses their emergence, drafting and implementation. It has been
      known that key requirements could only be fulfilled on a regional basis, the
      Leipzig University Department of Psychiatry being an outstanding example,
      although its staff worked rather autonomously of the Rodewisch Theses. The
      reasons for the different degree of success of these developments in individual
      areas are manifold, key reasons being the lack of stark political support and of
      opportunity to discuss shortcomings in mental health care, as in Western Germany,
      due to political circumstances in particular. There was no strong social basis
      and support as in Western democracies. 

PMID- 23868718
TI  - Demonstration of beam steering via dipole-coupled plasmonic spiral antenna.
AB  - Optical antennas have been utilized to tailor the emission properties of
      nanoscale emitters in terms of the intensity, directivity and polarization. In
      this letter, we further explore the capability of beam steering via the use a
      spiral plasmonic structure as a transmitting antenna. According to both numerical
      simulation and experimental observations, the beaming direction can be steered
      through introducing a displacement of the feeding point to the spiral antenna
      from the geometrical center. For a 3-turn Archimedes' spiral antenna,
      experimental results show that steering angles of 3 degrees  and 7 degrees  are
      obtainable when the excitation location is transversally shifted from the center
      by a displacement of 200 nm and 500 nm, respectively. Furthermore, the emitted
      photons carry spin angular momentum determined by the chirality of the spiral
      optical antenna. A steerable nanoscale spin photon source may find important
      applications in single molecule sensing, quantum optical information processing
      and integrated photonic circuits. 

PMID- 23868719
TI  - Adjective-noun order as representational structure: native-language grammar
      influences perception of similarity and recognition memory.
AB  - This article describes two experiments linking native-language grammar rules with
      implications for perception of similarity and recognition memory. In prenominal
      languages (e.g., English), adjectives usually precede nouns, whereas in
      postnominal languages (e.g., Portuguese), nouns usually precede adjectives. We
      explored the influence of such rules upon similarity judgments about, and
      recognition of, objects with multiple category attributes (one nominal attribute
      and one adjectival attribute). The results supported the hypothesized primacy
      effect of native-language word order such that nouns generally carried more
      weight for Portuguese speakers than for English speakers. This pattern was
      observed for judgments of similarity (i.e., Portuguese speakers tended to judge
      objects that shared a noun-designated attribute as more similar than did English
      speakers), as well as for false alarms in recognition memory (i.e., Portuguese
      speakers tended to falsely recognize more objects if they possessed a familiar
      noun attribute, relative to English speakers). The implications of such
      linguistic effects for the cognition of similarity and memory are discussed.

PMID- 23868720
TI  - H2 cleavage, hydride formation, and catalytic hydrogenation of imines with zinc
      complexes of C5Me5 and N-heterocyclic carbenes.

PMID- 23868721
TI  - LC-ESI-MS/MS analysis and pharmacokinetics of jolkinolide B, a potential
      antitumor active component isolated from Euphorbia fischeriana, in rat plasma.
AB  - A simple, specific and reproducible liquid chromatography-electrospray ionization
      mass spectrometry was developed and validated for the determination of
      jolkinolide B, a potential antitumor active component isolated from Euphorbia
      fischeriana, in rat plasma. Chromatographic separation was achieved on a Venusil
      MP-C18 column using an isocratic elution. Jolkinolide B and osthole (internal
      standard) were monitored by positive electrospray ionization in the selected
      reaction monitoring mode. Good linearity (r(2) > 0.996) was achieved by a
      weighted (1/x(2) ) linear least-squares regression over a concentration range of
      6.50-2600 ng/mL. The accuracy and precision of the assay were satisfactory and
      the method proved to be applicable to pharmacokinetics following a single
      intravenous bolus injection of jolkinolide B to rats.

PMID- 23868722
TI  - Characterisation and identification of dihydroindole-type alkaloids from
      processed semen strychni by high-performance liquid chromatography coupled with
      electrospray ionisation ion trap time-of-flight mass spectrometry.
AB  - INTRODUCTION: For centuries, Semen Strychni (the ripened seeds of Strychnos nux
      vomica) has been used extensively as a herbal medicine in Asian countries.
      However, the chemical composition of the dihydroindole-type alkaloids contained
      in processed Semen Strychni is not fully understood. OBJECTIVE: To develop an
      improved strategy using mass defect filtering (MDF) in combination with MS(n)
      analysis and theoretical calculations for identification and structural
      characterisation of dihydroindole-type alkaloids in processed Semen Strychni
      extracts. METHODS: The experimental work was conducted using a high-performance
      liquid chromatography coupled with electrospray ionisation ion trap time-of
      flight mass spectrometry (HPLC-ESI/IT-TOF/MS) system. Upon acquisition of full
      scan MS data, the potential dihydroindole-type alkaloids were screened using a
      well-defined mass defect range of 50 mDa. With the assistance of MS(n) analysis,
      the diagnostic fragment ions (DFIs) were used as primary screening references for
      targeting the characteristic analogues. For better discrimination of the isomers,
      quantum chemical calculations were utilised to provide additional structural
      information. RESULTS: Twenty-four dihydroindole-type alkaloids, including four
      that were previously not described, were tentatively identified. CONCLUSION: A
      new, rapid and sensitive method was developed for the discovery and
      characterisation of dihydroindole-type alkaloids in extracts of processed Semen
      Strychni. The successful application of this method indicates a potential for
      adaptation to other classes of natural product from other sources.

PMID- 23868723
TI  - Rapid and simple LC-MS/MS screening of 64 novel psychoactive substances using
      dried blood spots.
AB  - The range of novel psychoactive substances (NPS) including phenethylamines,
      cathinones, piperazines, tryptamines, etc. is continuously growing. Therefore,
      fast and reliable screening methods for these compounds are essential and needed.
      The use of dried blood spots (DBS) for a fast straightforward approach helps to
      simplify and shorten sample preparation significantly. DBS were produced from 10
      ul of whole blood and extracted offline with 500 ul methanol followed by
      evaporation and reconstitution in mobile phase. Reversed-phase chromatographic
      separation and mass spectrometric detection (RP-LC-MS/MS) was achieved within a
      run time of 10 min. The screening method was validated by evaluating the
      following parameters: limit of detection (LOD), matrix effect, selectivity and
      specificity, extraction efficiency, and short-term and long-term stability.
      Furthermore, the method was applied to authentic samples and results were
      compared with those obtained with a validated whole blood method used for routine
      analysis of NPS. LOD was between 1 and 10 ng/ml. No interference from matrix
      compounds was observed. The method was proven to be specific and selective for
      the analytes, although with limitations for 3-FMC/flephedrone and MDDMA/MDEA.
      Mean extraction efficiency was 84.6 %. All substances were stable in DBS for at
      least a week when cooled. Cooling was essential for the stability of cathinones.
      Prepared samples were stable for at least 3 days. Comparison to the validated
      whole blood method yielded similar results. DBS were shown to be useful in
      developing a rapid screening method for NPS with simplified sample preparation.

PMID- 23868724
TI  - Polymers with tunable side-chain amphiphilicity as non-hemolytic antibacterial
      agents.
AB  - Quaternized polymers mimicking the antimicrobial peptides were created by tuning
      the side-chain amphiphilicity using a first-time approach of post
      functionalization. They displayed excellent efficacy against pathogenic bacteria
      even in human plasma and membrane disruptive mode of action. The optimized
      polymers and degraded products were non-hemolytic. 

PMID- 23868725
TI  - Assessment of competitive ability of two Indian wheat cultivars under ambient O3
      at different developmental stages.
AB  - The concentrations of O3 are increasing, which may have potential adverse effects
      on crop yield. This paper deals with assessing the intraspecific variability of
      two wheat cultivars (PBW 343 and M 533) at different growth stages using open top
      chambers. Mean O3 concentrations were 50.2 and 53.2 ppb, and AOT40 values were 9
      and 12.1 ppm h, respectively, in 2008-2009 and 2009-2010. Reproductive stage
      showed higher AOT40 values (6.9 and 9.2 ppm h) compared to vegetative (2.23 and
      2.9 ppm h). Critical levels of a 3-month AOT 40 of 3 ppm h led to 6% yield
      reduction in two wheat cultivars for two consecutive years. Variations in
      photosynthesis rate, stomatal conductance (gs), Fv/Fm ratio, photosynthetic
      pigments, primary and secondary metabolites, morphological parameters, and yield
      attributes were measured at vegetative and reproductive stages. Reductions in
      number of leaves, leaf area, total biomass, root/shoot ratio, RGR, photosynthetic
      pigments, protein content, and Fv/Fm ratio in PBW 343 were more than M 533 at
      reproductive stage. Photosynthetic rate did not vary between the cultivars, but
      gs was higher in PBW 343 compared to M 533 under ambient O3. Higher total
      phenolics and peroxidase activity were recorded in M 533 at reproductive stage
      conferring higher resistance at latter age. Results of O3 resistance showed that
      M 533 was sensitive compared to PBW 343 during vegetative stage but developed
      more resistance at reproductive stage. PBW 343 with larger leaf area and high gs
      is more sensitive than M 533 with smaller leaf area and low gs. The study
      suggests that the sensitivity varied with plant growth stage, and the plant
      showing higher sensitivity during vegetative period developed more resistance
      during reproductive period due to higher defense mechanism. Though the yield
      reductions were same in both cultivars under ambient O3, the mechanism of
      acquiring the resistance is different between the cultivars.

PMID- 23868726
TI  - The use of olive-mill waste compost to promote the plant vegetation cover in a
      trace-element-contaminated soil.
AB  - The applicability of a mature compost as a soil amendment to promote the growth
      of native species for the phytorestoration of a mine-affected soil from a semi
      arid area (SE Spain), contaminated with trace elements (As, Cd, Cu, Mn, Pb and
      Zn), was evaluated in a 2-year field experiment. The effects of an inorganic
      fertiliser were also determined for comparison. Bituminaria bituminosa was the
      selected native plant since it is a leguminous species adapted to the particular
      local pedoclimatic conditions. Compost addition increased total organic-C
      concentrations in soil with respect to the control and fertiliser treatments,
      maintained elevated available P concentrations throughout the duration of the
      experiment and stimulated soil microbial biomass, while trace elements
      extractability in the soil was rather low due to the calcareous nature of the
      soil and almost unaltered in the different treatments. Tissue concentrations of P
      and K in B. bituminosa increased after the addition of compost, associated with
      growth stimulation. Leaf Cu concentration was also increased by the amendments,
      although overall the trace elements concentrations can be considered non-toxic.
      In addition, the spontaneous colonisation of the plots by a total of 29 species
      of 15 different families at the end of the experiment produced a greater
      vegetation cover, especially in plots amended with compost. Therefore, the use of
      compost as a soil amendment appears to be useful for the promotion of a
      vegetation cover and the phytostabilisation of moderately contaminated soils
      under semi-arid conditions. 

PMID- 23868728
TI  - Manifestations of non-planar adsorption geometries of lead pyrenocyanine at the
      liquid-solid interface.
AB  - In this work, we provide evidence for multiple non-planar adsorption geometries
      of a novel pyrenocyanine derivative at the liquid-solid interface under ambient
      conditions. When adsorbed at the organic liquid-solid interface, lead
      pyrenocyanine forms well-ordered monolayers that exhibit peculiar non-periodic
      contrast variation. The different contrast of the adsorbed molecules is
      attributed to dissimilar adsorption geometries which arise from the non-planar
      conformation of the molecules. The non-planarity of the molecular backbone in
      turn arises due to a combination of the angularly extended pyrene subunits and
      the presence of the large lead ion, which is too big to fit inside the central
      cavity and thus is located out of the aromatic plane. The two possible locations
      of the lead atom, namely below and above the aromatic plane, could be identified
      as depression and protrusion in the central cavity, respectively. The
      manifestation of such multiple adsorption geometries on the structure of the
      resultant monolayer is discussed in detail. The packing density of these 2D
      arrays of molecules could be tuned by heating of the sample wherein the molecular
      packing changes from a low-density, pseudo six-fold symmetric to a high-density,
      two-fold symmetric arrangement. Finally, a well-ordered two-component system
      could be constructed by incorporating C60 molecules in the adlayer of lead
      pyrenocyanine at the liquid-solid interface. 

PMID- 23868727
TI  - Inhibition of FAK and VEGFR-3 binding decreases tumorigenicity in neuroblastoma.
AB  - Neuroblastoma is the most common extracranial solid tumor of childhood and is
      responsible for over 15% of pediatric cancer deaths. Focal adhesion kinase (FAK)
      is a nonreceptor tyrosine kinase that is important in many facets of tumor
      development and progression. Vascular endothelial growth factor receptor-3 (VEGFR
      3), another tyrosine kinase, has also been found to be important in the
      development of many human tumors including neuroblastoma. Recent reports have
      found that FAK and VEGFR-3 interact, and we have previously shown that both of
      these kinases interact in neuroblastoma. We have hypothesized that interruption
      of the FAK-VEGFR-3 interaction would lead to decreased neuroblastoma cell
      survival. In the current study, we examined the effects of a small molecule,
      chloropyramine hydrochloride (C4), designed to disrupt the FAK-VEGFR-3
      interaction, upon cellular attachment, migration, and survival in two human
      neuroblastoma cell lines. We also utilized a murine xenograft model to study the
      impact of C4 upon tumor growth. In these studies, we showed that disruption of
      the FAK-VEGFR-3 interaction led to decreased cellular attachment, migration, and
      survival in vitro. In addition, treatment of murine xenografts with
      chloropyramine hydrochloride decreased neuroblastoma xenograft growth. Further,
      this molecule acted synergistically with standard chemotherapy to further
      decrease neuroblastoma xenograft growth. The findings from this current study
      help to further our understanding of the regulation of neuroblastoma
      tumorigenesis, and may provide novel therapeutic strategies and targets for
      neuroblastoma and other solid tumors of childhood.

PMID- 23868729
TI  - [Multimorbidity and inflammatory rheumatic diseases].

PMID- 23868730
TI  - [Multimorbidity in elderly rheumatic patients part 1].
AB  - An appropriate treatment of elderly rheumatic patients implements comprehensive
      diagnostics and exclusion diagnostics of e.g. coronary heart disease,
      osteoporosis, renal failure, diabetes mellitus type 2 and thyroid gland
      dysfunction. Furthermore, the complex disease situation might require the
      integration of other faculties or might be a reason for inpatient treatment. The
      complexity in the treatment of multimorbid elderly patients suffering from
      rheumatism not only rises with increasing age but also constitutes a considerable
      challenge due to existing incapacities and preceding as well as currently
      performed immunosuppressive therapies. The necessary treatment framework is
      outlined from the perspective of rheumatologists and geriatricians. Typical
      geriatric symptoms, such as malnutrition, immobility and frailty might be
      enhanced if multimorbidity is simultaneously present.

PMID- 23868731
TI  - [Comorbidity of rheumatic and hepatic diseases].
AB  - The correlation between rheumatic diseases and liver diseases is complex and
      often not given sufficient attention. There are, however, consequences for
      diagnosis and therapy. Rheumatic diseases can present with hepatic symptoms while
      liver diseases can exhibit rheumatic symptoms. Examples of liver diseases as a
      cause of rheumatic symptoms are viral hepatitis B and C, autoimmune hepatitis and
      hemochromatosis. As a result of rheumatic diseases, such as adult onset Still's
      disease and systemic lupus erythematosus, liver dysfunction can occur. Autoimmune
      hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis are
      directly associated with rheumatic diseases and have to be distinguished by way
      of differential diagnosis. During antirheumatic therapy, serious hepatotoxic side
      effects have to be expected. 

PMID- 23868732
TI  - [Multimorbidity in elderly rheumatic patients part 2].
AB  - While diseases, such as cardiovascular diseases and osteoporosis in the elderly
      are categorized as comorbidities of rheumatoid arthritis, elderly rheumatic
      patients are often additionally affected by thyroid dysfunctions and diabetes
      mellitus type 2, so that the risk of multimorbidity (coexistence of at least two
      chronic and/or acute diseases) will increase significantly in elderly patients
      already suffering from systemic rheumatic diseases. Restricted cognition,
      adherence or compliance may additionally complicate the treatment of elderly
      rheumatic patients. Furthermore, the pharmacokinetics of the elderly is another
      challenging task. Referring to selected aspects of geriatric pharmacotherapy, the
      use of certain substance classes is described in this context.

PMID- 23868734
TI  - Palliation of malignant tracheal stenosis with a second implantation of an
      expandable metallic stent under endotracheal intubation.
AB  - A 74-year-old man was admitted with respiratory failure and treated for
      tracheobronchial stenosis due to metastasis of renal cell carcinoma. It improved
      after implantation of an expandable metallic stent (EMS). One year later, the
      metastatic tumor at the near distal side of the EMS increased; eventually serious
      respiratory failure occurred again. However, the delivery catheter of EMS could
      not be inserted by the usual procedure because there was a strong
      tracheobronchial curve. Finally it passed along the inside of the endotracheal
      intubation tube. The respiratory failure was improved by the second implantation
      of EMS with the method of stent in stent. EMS is often effective in a case with a
      strong curve and twist of the trachea/bronchi. It was also considered one way of
      letting the delivery catheter pass inside the endotracheal intubation tube if the
      patient's respiratory condition was maintained. 

PMID- 23868733
TI  - Punishing unfairness: rewarding or the organization of a reactively aggressive
      response?
AB  - OBJECTIVES: The neural correlates of human cooperative behavior remain poorly
      understood. Previous work has suggested that increases in striatal activation
      while punishing unfair offers represents reward signaling. However, other regions
      are also implicated when punishing others, for example dorsomedial frontal cortex
      (dmFC), anterior insula cortex (AIC), and periaqueductal gray (PAG). Moreover,
      the response of other regions implicated in signaling reward, for example
      ventromedial prefrontal cortex (vmPFC) or posterior cingulate cortex (PCC), has
      not been systematically examined. EXPERIMENTAL DESIGN: Functional magnetic
      resonance imaging utilizing parametric modulation was conducted on 21 healthy
      adults participating in a social exchange paradigm. PRINCIPAL OBSERVATIONS:
      Participants showed significant positive modulation of activity as a function of
      delivered punishment in caudate, dmFC, AIC, and PAG; that is, higher punishments
      by participants of unsatisfactory offers were associated with increasing activity
      within these regions. However, participants showed significant negative
      modulation of activity as a function of delivered punishment in vmPFC and PCC;
      increases in punishment level by participants were associated with decreases in
      activity within these regions. CONCLUSIONS: The current data question whether
      caudate activity when punishing unfair offers should be considered to indicate
      the reward value of this punishment. Instead, this activity, in conjunction with
      activity within dmFC, AIC, and PAG, may represent the organization of an
      untypical, punishing response that represents a reactive aggressive response to
      provocation. Notably, an inverse, regulatory relationship between vmPFC and PAG
      activity has been previously implicated in the context of another stimulus for
      reactive aggression; looming threat (Mobbs et al. [2007]: Science 317:1079-1083).

PMID- 23868735
TI  - Case of disseminated vesicles of herpes zoster developing one day before the
      onset of local eruption in a hospitalized immunocompromised patient.
AB  - Disseminated herpes zoster is not rare in immunocompromised patient. It is
      defined as at least 20 lesions in multiple dermatomes that occur within a week of
      the onset of local eruption. Herein, we report that a case of disseminated
      vesicles of herpes zoster (HZ) that developed one day before the onset of local
      eruption in an immunocompromised patient. A 44 year-old Japanese male, who had
      been in the hospital with acute myelocytic leukemia, developed disseminated
      hemorrhagic vesicles of 5 to 10 mm in diameter. The next day, grouped vesicles,
      including hemorrhagic vesicles erupted on the right side of the second to third
      cervical (C2-C3) dermatomes. At this point, the diagnosis was made as
      disseminated herpes zoster. The activation of varicella-zoster virus (VZV) is
      believed to be due to waning of VZV-specific memory T cell responses. In our
      case, the memory immunity to VZV which had been increased by last episode of HZ
      might affect on the appearance of skin eruptions. 

PMID- 23868736
TI  - Methamphetamine-withdrawal stress activates PACAP-DBI pathway in rat salivary
      gland, resulting in inhibition of salivary secretion.
AB  - The purpose of this study was to investigate activation of inhibitory regulation
      pathways by methamphetamine (METH)-withdrawal stress in rat salivary gland. Our
      previous study showed that METH-withdrawal stress activated steroid biosynthesis
      and that pregnenolone produced during the early stage of this process inhibited
      salivary secretion. However, how this type of stress inhibits salivary secretion
      and the activation pathway of steroid biosynthesis in salivary gland remain to be
      clarified. In the present study, using an in vivo cannulation method, METH
      withdrawal stress decreased salivary secretion and increased expression of
      diazepam-binding inhibitor (DBI), an endogenous peripheral-type benzodiazepine
      receptor (PBR) agonist; Western blot and RT-PCR also showed increased expression
      of DBI mRNA in parotid, submandibular, and sublingual gland. In addition, METH
      withdrawal stress also elicited an increase in pituitary adenylate cyclase
      activating polypeptide (PACAP) and PBR mRNA, which is associated with DBI
      activity. These results suggest that METH-withdrawal stress activates a PACAP-DBI
      pathway in salivary gland, enhancing steroid genesis and inhibiting secretion. 

PMID- 23868737
TI  - Increase in antinociceptive effect of [leu5]enkephalin after intrathecal
      administration of mixture of three peptidase inhibitors.
AB  - OBJECTIVE: Previous in vitro studies have shown that the degradation of
      [Leu5]enkephalin during incubation with cerebral membrane preparations is almost
      completely prevented by a mixture of three peptidase inhibitors such as
      amastatin, captopril, and phosphoramidon. The present in vivo study was performed
      to examine the antinociceptive effect of [Leu5]enkephalin administered
      intrathecally under pretreatment with these three peptidase inhibitors. METHODS:
      A tail-flick test was used to determine the nociceptive threshold after
      administration of [Leu5]enkephalin. The time-course profiles of the latency to
      flick the tail and the area under the time response curve were evaluated for the
      antinociceptive action of the drug. RESULTS: The antinociceptive effect of
      [Leu5]enkephalin administered intrathecally on the tail-flick test was increased
      more than 100-fold under i.t. pretreatment with three peptidase inhibitors. The
      antinociceptive effect produced by [Leu5]enkephalin in rats pretreated with any
      single peptidase inhibitor increased antinociception compared to that with
      saline. The antinociceptive potency of [Leu5]enkephalin under pretreatment with
      any combination of two peptidase inhibitors was smaller than that in rats
      pretreated with three peptidase inhibitors together. These results indicate that
      any residual single peptidase inactivates significant amounts of
      [Leu5]enkephalin. CONCLUSION: The present data, together with those of earlier
      studies, clearly demonstrate that amastatin-, captopril-, and phosphoramidon
      sensitive enzymes play an important role in the inactivation of [Leu5]enkephalin
      administered intrathecally in rat.

PMID- 23868738
TI  - Amplitude spectral area: predicting the success of electric shock delivered by
      defibrillators with different waveforms.
AB  - OBJECTIVES: Prolonged ventricular fibrillation (VF) is associated with a low rate
      of return of spontaneous circulation (ROSC) following electric shock. Moreover,
      electric shock that does not reestablish spontaneous circulation causes
      myocardial dysfunction even if ROSC is subsequently achieved. Amplitude spectral
      area (AMSA), calculated by analysis of VF waveforms immediately before electric
      shock, is considered to predict the outcome of electric shock. This study aimed
      to evaluate the prognostic value of AMSA in relation to waveforms of
      defibrillators in prehospital settings. METHODS: The AMSA values of 81 patients
      with VF confirmed by ambulance crews were compared according to the type of
      defibrillators with different waveforms and between those with and without ROSC.
      RESULTS: With a biphasic defibrillator, the mean AMSA was significantly different
      between the 14 patients who achieved ROSC (25.3 +/- 9.5 mV-Hz) and the 43
      subjects who did not achieve ROSC (15.4 +/- 8.1 mV-Hz; p = 0.0006). No
      significant difference was seen in the corresponding values when a monophasic
      defibrillator was used, at 19.1 +/- 2.4 mV-Hz for 3 ROSC patients and 16.1 +/-
      7.5mV-Hz for 21 non-ROSC patients. CONCLUSION: AMSA may serve as a predictive
      measure for ROSC following electric shock delivered by a biphasic defibrillator.

PMID- 23868739
TI  - Rare variant of inguinal hernia, interparietal hernia and ipsilateral abdominal
      ectopic testis, mimicking a spiegelian hernia. Case report.
AB  - We report a case in which the combination of an interparietal inguinal hernia and
      ipsilateral ectopic testicle mimicked a spigelian hernia. The patient was a 22
      day-old boy who presented with a reducible mass that extended from the right
      lumbar region to the iliac fossa region. The right testis was palpable in the
      right lumbar region. Ultrasonography and magnetic resonance imaging revealed that
      a small bowel had herniated through the inguinal region below the external
      oblique aponeurosis. Surgery was performed when the patient was 23 months old.
      Laparoscopic examination to identify the hernia orifice revealed that it was the
      deep inguinal ring, and the testicular vessels and the vas deferens passed
      beneath the hernia sac. An inguinal incision was made, and a hernia sac was
      observed passing through the deep inguinal ring and extending superiorly below
      the aponeurosis. The testis was found in the hernia sac. Traditional inguinal
      herniorrhaphy and traditional orchidopexy were performed, and the postoperative
      course was uneventful. It is difficult to understand the surgical anatomy of
      interparietal hernias, but once the surgical anatomy is understood, surgical
      repair is simple. We report the case with a review of the literature and also
      emphasize that laparoscopic exploration is helpful during surgery. 

PMID- 23868740
TI  - Assessing the risk of birth defects associated with exposure to highly active
      anti-retroviral therapy during organogenesis in rats.
AB  - The use of anti-retroviral drugs during pregnancy has increased since the
      demonstration of reduction of mother-to-child transmission of HIV with highly
      active antiretroviral therapy (HAART). The risk of HAART cannot be ruled out;
      data are generally limited or varied. This study intends to thoroughly assess the
      teratogenic effect of HAART on the organogenesis stage of fetal development using
      animal model. Pregnant rats were divided into 13 groups with 12 animals per
      group. The therapeutic doses of drug administration were done to simulate the
      treatment pattern in APIN HIV/AIDS Clinic of the University of Lagos Teaching
      Hospital, Nigeria (find detailed treatment groups in methodology). Six rats in
      each group were randomly selected and sacrificed on day 20 by cervical
      dislocation prior to day 21 of gestation and the foetuses were harvested through
      abdominal incision for physical examination. Blood samples were collected from
      the 1st filial rats of the remaining six animals for biochemical and
      haematological examination. The liver, kidney, heart and brain of all the
      sacrificed animals were used for histopathological examination. There were
      significant (P <= 0.05) low birth weights of the foetuses of the animals that
      were treated with HAART. Results also revealed a reduction (P <= 0.05) in the
      platelets counts, WBC and RBC of most treatment groups at the first filial
      generation. Significant (P <= 0.05) elevations in the levels of AST and UA in the
      foetuses of the animals treated with HAART were also observed. It can be
      concluded that administration of single and combined antiretrovirals have
      potential teratogenic effect. 

PMID- 23868741
TI  - Quetiapine reduces irritability and risk of suicide in patients with agitated
      depression.
AB  - Patients who suffer from agitated depression accompanied by psychomotor agitation
      and irritability are prone to suicidal ideation and attempts and must therefore
      be diagnosed and treated with utmost care. Clinically, there have been more than
      a few cases of suicidal attempts that seemed to have been provoked by careless
      prescription of antidepressant medication. In the present study, administration
      of quetiapine to 3 patients in the acute phase of agitated depression resulted in
      rapid improvement in irritability and alleviation of depression. Depression in
      these 3 patients was caused by chronic (persistent) anxiety and tension. During
      the acute phase, the patients evidenced psychomotor agitation and irritability,
      often experiencing a sudden, overwhelming urge to commit suicide. Findings from
      the present study suggest that treatment with quetiapine in patients with this
      type of agitated depression can quickly alleviate symptoms of anxiety and
      irritability and reduce the risk of suicide. 

PMID- 23868742
TI  - Natural infection and phylogenetic classification of Leishmania spp. infecting
      Rhombomys opimus, a primary reservoir host of zoonotic cutaneous leishmaniasis in
      Northeast Iran.
AB  - BACKGROUND: In the northeast and central parts of Iran, Rhombomys opimus (great
      gerbil) is the primary reservoir host of zoonotic cutaneous leishmaniasis (ZCL).
      This study used both parasitological and molecular methods to identify Leishmania
      spp. and their different haplotypes that were circulating in the great gerbil
      populations in ZCL foci from northeastern Iran. METHODS: A cross-sectional study
      using microscopy, culturing and molecular methods was conducted to detect
      Leishmania parasites in 194 live R. opimus in ZCL foci from northeastern Iran
      during 2010-2011. RESULTS: Leishmania spp. were found in 38.1% (74/194) of the
      samples by microscopy and in 41.2% (80/194) by culturing. Small papules and skin
      thickening on the upper edge of the ears were observed in 25 (12. 9%) of the R.
      opimus. PCR-RFLP and PCR direct sequencing of internal transcribed spacer 1
      (ITS1) rRNA showed similar infection rates for L. major and L. turanica in 60
      eligible R. opimus, only one mixed infection containing both L. major and L.
      turanica was found. Phylogenetic analysis was conducted using the ITS1 sequences
      of 32 isolates that were successfully aligned by comparison of their base
      sequences with the ITS1 DNA sequence database using ClustalW and MEGA5. The
      samples were classified into monophyletic clusters (>97% bootstrap). Six
      haplotypes were observed for L. major and seven for L. turanica. CONCLUSION: In
      northeast Iran, L. major, and L. turanica naturally circulate in R. opimus, and
      L. major/L. turanica co-infections also exist. Phylogenetic analysis suggested
      that Leishmania spp. isolated from R. opimus are not a monophyletic group.

PMID- 23868743
TI  - Critical phase among patients with dengue fever during the 2010 outbreak in
      Nepal.
AB  - BACKGROUND: Dengue virus infection has become an increasingly serious threat to
      public health in Nepal. Detection and/or serotyping of dengue virus has been
      reported in the past; however, little is known about the critical phase among
      dengue patients in Nepal. METHODS: Rapid immunochromatographic tests and reverse
      transcription PCR (RT-PCR) were performed in order to diagnosis dengue fever.
      Ultrasonographic and chest radiography were used to identify the plasma leakage
      phase. RESULTS: Of the total 264 patients with dengue, 8.7% (23/264) were
      admitted during the critical phase; 82.6% (19/23) of the patients were between 20
      and 44 years of age. CONCLUSION: Physicians need to be vigilant and attentive to
      young adult patients with dengue fever.

PMID- 23868744
TI  - Small mammals as hosts of Leishmania spp. in a highly endemic area for zoonotic
      leishmaniasis in North-Eastern Brazil.
AB  - BACKGROUND: Leishmania parasites cause leishmaniasis in humans and animals
      worldwide. These parasites are transmitted by phlebotomine sand flies, which
      become infected upon feeding on an infected mammalian host. We assessed the
      occurrence of Leishmania infection in small mammals in an area of cutaneous and
      visceral leishmaniasis endemicity. METHODS: A total of 180 small mammals were
      trapped in 2003 and 2006 in a rural area in north-eastern Brazil. Spleen and skin
      samples from these animals were assessed by two PCR protocols, one targeting
      Leishmania (Viannia) spp. and other Leishmania (Leishmania) infantum.
      Additionally, serum samples were tested by an immunochromatographic test with
      rK39 as antigen. RESULTS: Overall, 23.2% (38/164) of the animals were positive to
      L. (V.) spp. and 8.8% (14/160) to L. (L.) infantum). Five animals of four species
      (Didelphis albiventris, Nectomys squamipes, Rattus rattus and Holochilus
      sciureus) were positive by both PCR protocols, an overall co-infection rate of
      2.5%. By serology, 5% (7/139) of the animals were positive, but all of them were
      PCR-negative. An isolate obtained from a water rat (N. squamipes) was
      characterized as L. (V.) braziliensis (zymodeme Z-74). CONCLUSIONS: This study
      reinforces the involvement of different small mammals (e.g., N. squamipes, R.
      rattus and H. scieurus) in the transmission cycles of L. (V.) braziliensis and L.
      (L.) infantum in north-eastern Brazil. The finding of L. (V.) braziliensis
      infection in black rats suggests a rapid process of adaptation of a New World
      Leishmania species to an Old World rodent and raises interesting questions
      regarding the co-evolution of these parasites and their vertebrate hosts.

PMID- 23868745
TI  - Circulating miR-130b mediates metabolic crosstalk between fat and muscle in
      overweight/obesity.
AB  - AIMS/HYPOTHESIS: Adipose tissue is a dynamic endocrine organ that regulates whole
      body energy homeostasis through the secretion of signalling molecules. Recent
      reports suggest that secreted microRNAs (miRNAs) may function as biologically
      active molecules for intercellular communication. This study aims to identify
      obesity-related circulating miRNA that could be secreted from adipocytes and to
      explore its possible role in the pathogenesis of metabolic diseases. METHODS:
      Real-time RT-PCR was used to evaluate the circulating level of miR-130b in mouse
      models of obesity as well as in humans. Luciferase assay and immunoblotting were
      used to verify the miRNA target. The effect of miR-130b on mouse peroxisome
      proliferator-activated receptor gamma coactivator-1alpha was also investigated by
      electrogene transfer. RESULTS: The circulating level of miR-130b was elevated in
      mouse models of obesity as well as in obese Chinese individuals. More
      interestingly, the circulating level of miR-130b was positively correlated with
      BMI. Moreover, circulating miR-130b was a better predictor of the metabolic
      syndrome than was triacylglycerol level. Mechanistically, adipocytes secreted miR
      130b during adipogenesis. TGF-beta, which is proportionately increased with
      obesity, stimulated miR-130b secretion from adipocytes. Furthermore, miR-130b was
      able to target muscle cells and reduce the expression of its direct target gene,
      PGC-1alpha (also known as PPARGC1A), which plays a key role in lipid oxidation in
      muscle. CONCLUSIONS/INTERPRETATION: Circulating miR-130b reflects the degree of
      obesity and could serve as a potential biomarker for hypertriacylglycerolaemia
      and metabolic syndrome. Circulating miR-130b could function as a metabolic
      mediator for adipose-muscle crosstalk and might be involved in the pathogenesis
      of obesity-associated metabolic diseases.

PMID- 23868746
TI  - Evaluation of cytomegalovirus (CMV)-specific T-cell immunity for the assessment
      of the risk of active CMV infection in non-immunosuppressed surgical and trauma
      intensive care unit patients.
AB  - The current study was designed to assess the predictive value of the evaluation
      of cytomegalovirus (CMV)-specific T-cell immunity early following admission to
      the intensive care unit for inferring the risk of active CMV infection in non
      immunosuppressed surgical and trauma patients. A total of 31 CMV-seropositive
      patients were included. Patients were screened for the presence of CMV DNA in
      plasma and in tracheal aspirates by real-time PCR. Enumeration of CMV pp65 and IE
      1-specific IFN-gamma CD8(+) and CD4(+) T cells was performed by flow cytometry
      for intracellular cytokine staining. Virological and immunological monitoring was
      conducted once or twice a week. Active CMV infection occurred in 17 out of 31
      patients. Undetectable levels of pp65 and IE-1-specific IFN-gamma CD8(+) and
      CD4(+) T-cell subsets cells were observed in 10 patients who developed active CMV
      infection and in one who did not (at a median of 2 days following ICU admission).
      Peak CMV DNA loads in both tracheal aspirates and plasma were substantially
      higher (P = 0.018 and P = 0.091, respectively) in patients with undetectable IFN
      gamma T-cell responses than in patients with detectable responses. The expansion
      of both CMV-specific T-cell subsets following detection of active CMV infection
      was demonstrated in 9 out of 14 patients with active CMV infection. In
      conclusion, the evaluation of CMV pp65 and IE-1-specific IFN-gamma-producing
      CD8(+) and CD4(+) T cells early following ICU admission may allow the
      identification of patients most at risk of either having or developing an episode
      of active CMV infection, particularly those associated with high-level virus
      replication.

PMID- 23868747
TI  - Life shocks and homelessness.
AB  - We exploited an exogenous health shock-namely, the birth of a child with a severe
      health condition-to investigate the effect of a life shock on homelessness in
      large cities in the United States as well as the interactive effects of the shock
      with housing market characteristics. We considered a traditional measure of
      homelessness, two measures of housing instability thought to be precursors to
      homelessness, and a combined measure that approximates the broadened
      conceptualization of homelessness under the 2009 Homeless Emergency Assistance
      and Rapid Transition to Housing Act (2010). We found that the shock substantially
      increases the likelihood of family homelessness, particularly in cities with high
      housing costs. The findings are consistent with the economic theory of
      homelessness, which posits that homelessness results from a conjunction of
      adverse circumstances in which housing markets and individual characteristics
      collide. 

PMID- 23868748
TI  - Multiple imputation of missing covariates in NONMEM and evaluation of the
      method's sensitivity to eta-shrinkage.
AB  - Multiple imputation (MI) is an approach widely used in statistical analysis of
      incomplete data. However, its application to missing data problems in nonlinear
      mixed-effects modelling is limited. The objective was to implement a four-step MI
      method for handling missing covariate data in NONMEM and to evaluate the method's
      sensitivity to eta-shrinkage. Four steps were needed; (1) estimation of empirical
      Bayes estimates (EBEs) using a base model without the partly missing covariate,
      (2) a regression model for the covariate values given the EBEs from subjects with
      covariate information, (3) imputation of covariates using the regression model
      and (4) estimation of the population model. Steps (3) and (4) were repeated
      several times. The procedure was automated in PsN and is now available as the
      mimp functionality ( http://psn.sourceforge.net/ ). The method's sensitivity to
      shrinkage in EBEs was evaluated in a simulation study where the covariate was
      missing according to a missing at random type of missing data mechanism. The eta
      shrinkage was increased in steps from 4.5 to 54%. Two hundred datasets were
      simulated and analysed for each scenario. When shrinkage was low the MI method
      gave unbiased and precise estimates of all population parameters. With increased
      shrinkage the estimates became less precise but remained unbiased. 

PMID- 23868749
TI  - Impact of osmotically active excipients on bioavailability and bioequivalence of
      BCS class III drugs.

PMID- 23868750
TI  - Prediction of prostate cancer from prostate biopsy in Chinese men using a genetic
      score derived from 24 prostate cancer risk-associated SNPs.
AB  - BACKGROUND: Twenty-four prostate cancer (PCa) risk-associated single nucleotide
      polymorphisms (SNPs) in Chinese men have been cataloged. We evaluated whether
      these SNPs can independently predict outcomes of prostate biopsy, and improve the
      predictive performance of existing clinical variables. METHODS: Three hundred
      eight consecutive patients that underwent prostate biopsy for detection of PCa at
      Huashan Hospital, Shanghai, China between April 2011 and August 2012 were
      recruited. Clinical variables such as serum prostate-specific antigen (PSA)
      levels and peripheral blood samples were collected prior to a 10-core biopsy. A
      genetic score based on these 24 PCa associated SNPs was calculated for each
      individual. RESULTS: Among 308 patients underwent prostate biopsy, 141 (45.8%)
      were diagnosed with PCa. Genetic score was significantly higher in patients with
      PCa (median = 1.30) than without (median = 0.89), P = 3.81 * 10(-6). The
      difference remained significant after adjusting for age and total PSA, P = 0.007.
      The PCa detection rate increased with increasing genetic score; 26.3%, 43.2%, and
      60.0% for men with lower (<0.5), average (0.5-1.5), and higher (>1.5) genetic
      score, respectively, P(-trend)  = 0.0003. For patients with moderately elevated
      PSA levels (1.6-20 ng/ml), the PCa detection rate was 31.2% overall and was
      16.7%, 31.2%, and 40.9% for men with lower (<0.5), average (0.5-1.5), and higher
      (>1.5) genetic score, respectively, P(-trend)  = 0.03. For patients with PSA >=
      20 ng/ml, however, the PCa detection rates were high (>69%) regardless of genetic
      score. CONCLUSION: A genetic score based on PCa risk-associated SNPs is an
      independent predictor of prostate biopsy outcomes in Chinese men and may be
      helpful to determine the need for prostate biopsy among patients within a "gray
      zone" of PCa risk.

PMID- 23868751
TI  - Photodissociation and dissociative photoionization mass spectrometry of proteins
      and noncovalent protein-ligand complexes.

PMID- 23868752
TI  - Pediatric subcutaneous panniculitis-like T-cell lymphoma with features of
      hemophagocytic syndrome.

PMID- 23868753
TI  - Recyclable porous polymer-supported copper catalysts for Glaser and Huisgen 1,3
      diolar cycloaddition reactions.
AB  - A family of polymer-attached phenanthrolines was prepared from solvothermal
      copolymerization of divinylbenzene with N-(1,10-phenanthroline-5-yl)acrylamide in
      different ratios. The polymer-supported copper catalysts were obtained through
      typical impregnation with copper(II) salts. The polymers and supported copper
      catalysts have been characterized by N2 adsortion, scanning electron microscopy
      (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis
      (TG); they exhibit a high surface area, hierarchical porosity, large pore volume,
      and high thermal and chemical stabilities. The copper catalyst has proved to be
      highly active for Glaser homocoupling of alkynes and Huisgen 1,3-diolar
      cycloaddition of alkynes with benzyl azide under mild conditions at low catalyst
      loading. The heterogeneous copper catalyst is more active than commonly used
      homogeneous and nonporous polystyrene-supported copper catalysts. In particular,
      the catalyst is easily recovered and can be recycled at least ten times without
      any obvious loss in catalytic activity. Metal leaching was prevented due to the
      strong binding ability of phenanthroline and products were not contaminated with
      copper, as determined by ICP analysis. 

PMID- 23868754
TI  - Variability of cannabis potency in the Venice area (Italy): a survey over the
      period 2010-2012.
AB  - Cannabis is the most widely used illicit substance globally, with an estimated
      annual prevalence in 2010 of 2.6-5.0% of the adult population. Concerns have been
      expressed about increases in the potency of cannabis products. A high
      tetrahydrocannabinol (THC) content can increase anxiety, depression, and
      psychotic symptoms, and can increase the risk of dependence and adverse effects
      on the respiratory and cardiovascular systems in regular users. The aim of this
      study was to report statistical data about the potency of cannabis products
      seized in the north-east of Italy, in a geographical area centred in Venice and
      extending for more than 10,000  km(2) with a population of more than two million,
      by investigating the variability observed in THC levels of about 4000 samples of
      cannabis products analyzed over the period 2010-2012. Overall median THC content
      showed an increasing trend over the study period from about 6.0% to 8.1% (6.2
      8.9% for cannabis resin, 5.1-7.6% for herbal cannabis). The variation in the THC
      content of individual samples was very large, ranging from 0.3% to 31% for
      cannabis resin and from 0.1 to 19% for herbal cannabis. Median CBN:THC ratios
      showed a slightly decreasing trend over the study period, from 0.09 (2010) to
      0.03 (2012), suggesting an increasing freshness of submitted materials. Median
      CBD:THC ratios also showed a decreasing trend over the study from about 0.52
      (2010) to 0.18 (2012), likely due to the increase in submissions of materials
      from indoor and domestic cultivation with improved breeding methods.

PMID- 23868755
TI  - Efficient polymer solar cells based on benzothiadiazole and alkylphenyl
      substituted benzodithiophene with a power conversion efficiency over 8%.
AB  - A new copolymer PBDTP-DTBT based on benzothiadiazole and alkylphenyl substituted
      benzodithiophene is synthesized and characterized. The correlation of the
      evolution of the morphology and photovoltaic performance is investigated. The
      power conversion efficiency of the polymer solar cells based on PBDTP-DTBT/PC71
      BM (1:1.5, w/w) reaches up to 8.07%, under the irradiation of AM 1.5G, 100
      mW/cm(2) . 

PMID- 23868756
TI  - Sparse partial-least-squares discriminant analysis for different geographical
      origins of Salvia miltiorrhiza by (1) H-NMR-based metabolomics.
AB  - INTRODUCTION: (1) H nuclear magnetic resonance (NMR) spectroscopy has clear
      advantages in respect of detecting various primary and secondary metabolites in
      plants simultaneously, non-targeted and non-destructively. OBJECTIVE: To
      establish a method for detecting both primary and secondary metabolites in Salvia
      miltiorrhiza and screening potential geographical biomarkers effectively.
      METHODS: Primary and secondary metabolites of S. militiorrhiza were detected and
      identified by (1) H-NMR fingerprint. Sparse partial-least-squares discriminant
      analysis (sPLS-DA) was undertaken for classification and variable selection in a
      one-step procedure and the classification error rates were implemented to
      estimate the cluster validation of sPLS-DA. Potential candidate metabolites by
      characterised different geographical origins of S. miltiorrhiza were identified
      according to the sparse loading vectors. The levels of these metabolites were
      quantified and evaluated by Kruskal-Wallis tests and also showed significant
      difference. RESULTS: Twenty-six primary and secondary metabolites were identified
      in samples from different regions. The results suggest that malonate and
      succinate can be possibly recognised as the key markers for discriminating the
      geographical origin of S. miltiorrhiza based on the regulation and influence on
      the root respiratory rates of plants. CONCLUSION: (1) H-NMR metabolic profiling
      combination with PLS-DA provided a very efficient and visualised representation
      of similarities and dissimilarities between S. miltiorrhiza samples.

PMID- 23868757
TI  - Riboflavin depletion of intestinal cells in vitro leads to impaired energy
      generation and enhanced oxidative stress.
AB  - BACKGROUND: Riboflavin is an essential component of the human diet, with an
      established role for its derivative cofactors in oxidative metabolism. Our
      previous in vivo data suggest that riboflavin may act as a signalling molecule in
      the intestinal lumen, regulating crypt development and cell turnover. Our in
      vitro studies in riboflavin-depleted intestinal cells in culture indicate that
      riboflavin depletion impairs normal mitosis. METHODS: The aim of the study was to
      establish an improved intestinal cell model of riboflavin depletion using the
      structural analogue of riboflavin, lumiflavin (7,8,10-trimethyl-isoalloxazine)
      and to determine effects on cell function. The study was conducted using three
      intestinal cell lines, Caco-2, HCT116 and HT29 cells. RESULTS: Cell growth was
      inhibited in all three cell lines, in a lumiflavin concentration-dependent
      manner. Riboflavin depletion was confirmed through a significant decrease in
      intracellular riboflavin concentrations in Caco-2 and HT29 cell lines and a
      significant increase in the activation coefficient for the flavin adenine
      dinucleotide-dependent enzyme glutathione reductase. Riboflavin depletion led to
      a significant reduction in intracellular ATP concentration, and an enhanced
      generation of reactive oxygen species was also observed in response to riboflavin
      depletion, in all cell lines; effects were at least fivefold greater in Caco-2
      cells than other cells. Riboflavin-depleted Caco-2 and HCT116 cells also showed
      an irreversible loss of proliferative potential. CONCLUSIONS: A model system of
      intracellular riboflavin depletion in intestinal epithelial cells has been
      developed. Riboflavin depletion induced by lumiflavin results in oxidative stress
      and a disruption of energy generation, which may contribute to observed effects
      on cell proliferation.

PMID- 23868758
TI  - Persistent mechanical allodynia positively correlates with an increase in
      activated microglia and increased P-p38 mitogen-activated protein kinase
      activation in streptozotocin-induced diabetic rats.
AB  - BACKGROUND: In experimental early painful diabetic neuropathy, persistent
      hyperglycaemia induces dys-regulated sodium channel (Navs) expression in the
      dorsal root ganglion (DRG) and activates microglia in the spinal dorsal horn
      (SDH). However, information on diabetes-induced chronic neuropathic pain is
      limited. Therefore, we investigated abnormal Navs in the DRG and activated glial
      cells in the SDH of diabetic rats with chronic neuropathic pain. METHODS: Sixty
      six rats were divided into diabetic and control groups: control rats (n = 18; 1
      mL of normal saline via the right femoral vein) and diabetic rats [n = 48; 60
      mg/kg streptozotocin (STZ) via the right femoral vein]. Hindpaw behavioural
      tests, Navs expression in the DRG, activation of glial cells in the SDH and the
      number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6
      months following saline and STZ administration. RESULTS: All diabetic rats
      exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased
      withdrawal threshold to mechanical stimuli but had blunted responses to thermal
      stimuli. Consistent up-regulation of Nav1.3 and down-regulation of Nav1.8 was
      observed. Microglial cells were activated early in the SDH and lasted for 6
      months. A positive correlation between mechanical allodynia, Nav1.3 and
      microglial activation was observed. In addition, microglia activation in the SDH
      of STZ-induced diabetes was mediated, in part, by phosphorylation of p-38 mitogen
      activated protein kinase. CONCLUSIONS: Diabetic rats showed hindpaw mechanical
      allodynia for 6 months. Persistent mechanical allodynia was positively associated
      with sustained increased activation of Nav1.3 and increased p38 phosphorylation
      in activated microglia.

PMID- 23868759
TI  - Guidelines on the use of therapeutic apheresis in clinical practice-evidence
      based approach from the Writing Committee of the American Society for Apheresis:
      the sixth special issue.
AB  - The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is
      charged with reviewing, updating and categorizating indications for therapeutic
      apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the
      committee has incorporated systematic review and evidence-based approach in the
      grading and categorization of indications. This Sixth Edition of the ASFA Special
      Issue has further improved the process of using evidence-based medicine in the
      recommendations by consistently applying the category and GRADE system
      definitions, but eliminating the "level of evidence" criteria (from the
      University HealthCare Consortium) utilized in prior editions given redundancy
      between GRADE and University HealthCare Consortium systems. The general layout
      and concept of a fact sheet that was utilized in the Fourth and Fifth Editions,
      has been largely maintained in this edition. Each fact sheet succinctly
      summarizes the evidence for the use of therapeutic apheresis in a specific
      disease entity. This article consists of 78 fact sheets (increased from 2010) for
      therapeutic indications in ASFA categories I through IV, with many diseases
      categorized having multiple clinical presentations/situations which are
      individually graded and categorized.

PMID- 23868760
TI  - [Psychiatry and the media; some reflections on the DSM-5 introduction].

PMID- 23868761
TI  - [Effects on scale and confidence intervals as alternatives to p < 0.05].
AB  - BACKGROUND: Researchers and reviewers often use the conventional p < 0.05 as
      threshold in statistical tests. In many cases, however, the interpretation of p
      values is incorrect. AIM: To explain where the 5% norm originates, identify the
      interpretation problems that often arise and suggest some alternatives. METHOD:
      On the basis of recent literature we examine the meaning and origin of the p <
      0.05 norm. We looked closely at entire articles and short reports in the
      Tijdschrift voor Psychiatrie, starting with the Jubilee issue of 2008, in order
      to find examples of methodological problems relating to the routine use of p
      values. RESULTS: We found several examples of the problematic use of p-values;
      these included the testing of a priori unlikely, or even impossible null
      hypotheses, the reporting of small effects calculations based on erroneous
      assumptions, and incorrect interpretations of statistical parameters and p
      values. CONCLUSION: Research in psychiatry, like research in other disciplines,
      attaches too much weight to p-values. Guidelines for authors should advise
      authors to focus explicitly on effect sizes, confidence intervals and the scale
      on which the results are presented.

PMID- 23868762
TI  - [Reporting statistical measures in the Tijdschrift voor Psychiatrie: is there a
      need for adopting statistical guidelines?].

PMID- 23868763
TI  - [Suicide: a medico-historical exploration].
AB  - BACKGROUND: The recent rise of suicide rates internationally clearly indicates
      that the medical profession needs to give more attention to suicidality. AIM: To
      construct a medico-historical framework for the concepts of suicide and
      suicidality. METHOD: The study is based on articles referred to in PubMed and on
      the historical literature. RESULTS: Throughout history, the legal, stoic,
      medical, and sociological perspectives have all left their own unique stamp on
      the conceptualisation of suicide and suicidality. CONCLUSION: Recent initiatives
      in the Netherlands such as 113Online and the Multi-disciplinary guideline for
      diagnosis and treatment of suicidal behaviour constitute apt responses to the
      alarming rise of suicide rates, but it is not clear to what extent these
      initiatives will be able to counterbalance the interpersonal and social-economic
      mechanisms which appear to have determined suicide rates in the course of
      history.

PMID- 23868764
TI  - [Reaction on 'the use of psychodiagnostic tests in forensic psychiatric reports
      within the framework of internment. An exploratory study of records on internees
      in the judicial district of Ghent'].

PMID- 23868765
TI  - Myelodysplastic syndrome (MDS)-associated cytogenetic abnormalities in pediatric
      chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is very rare in the pediatric population. We
      report the case of a 2-year-old female with CML and concurrent myelodysplastic
      syndrome (MDS) associated cytogenetic abnormalities. The co-existence of t(9;22)
      and chromosomal deletions that are associated with MDS poses a unique diagnostic
      challenge. Given the reported association of t(9;22) and genomic instability, we
      hypothesize that the chromosomal deletions represent clonal evolution of the CML.

PMID- 23868768
TI  - Dependence of the distribution constant in liquid-liquid partition equilibria on
      the van der Waals molecular surface area.
AB  - The direct calculation of free energy of interactions between a solute j and two
      immiscible liquids shows a linear dependence between the (logarithm of) the
      distribution constant in liquid-liquid partition equilibrium log K(j) and the van
      der Waals surface area of the solute. The study provides a thermodynamic proof
      for the formula log K(BA,j) = c1 log K(BC,j) + c2 that describes the linear
      dependence between (the logarithm of) the distribution constant for a solute j in
      a solvent system (B/A) and (the logarithm of) the distribution constant for the
      same solute in a different solvent system (B/C). This relation has been well
      proven by various experimental studies and it is frequently used in liquid
      chromatographic separations as well as in liquid-liquid extractions, but was not
      explained previously based on thermodynamic results. The theory was verified
      using the prediction of octanol/water distribution constants log K(ow) for a wide
      range of molecules, including hydrocarbons and compounds with a variety of
      functional groups. The results have also been verified for the distribution
      constants in other solvent systems. The expression for the distribution constant
      obtained in this study also gives a theoretical base for the additive fragment
      methodology used for the prediction of log K(ow).

PMID- 23868769
TI  - A feature selection method for multivariate performance measures.
AB  - Feature selection with specific multivariate performance measures is the key to
      the success of many applications such as image retrieval and text classification.
      The existing feature selection methods are usually designed for classification
      error. In this paper, we propose a generalized sparse regularizer. Based on the
      proposed regularizer, we present a unified feature selection framework for
      general loss functions. In particular, we study the novel feature selection
      paradigm by optimizing multivariate performance measures. The resultant
      formulation is a challenging problem for high-dimensional data. Hence, a two
      layer cutting plane algorithm is proposed to solve this problem, and the
      convergence is presented. In addition, we adapt the proposed method to optimize
      multivariate measures for multiple-instance learning problems. The analyses by
      comparing with the state-of-the-art feature selection methods show that the
      proposed method is superior to others. Extensive experiments on large-scale and
      high-dimensional real-world datasets show that the proposed method outperforms l1
      SVM and SVM-RFE when choosing a small subset of features, and achieves
      significantly improved performances over SVM(perf) in terms of F1-score.

PMID- 23868767
TI  - Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera
      cancer terminator virus (Ad.5/3-CTV).
AB  - Few options are available for treating patients with advanced prostate cancer
      (PC). As PC is a slow growing disease and accessible by ultrasound, gene therapy
      could provide a viable option for this neoplasm. Conditionally replication
      competent adenoviruses (CRCAs) represent potentially useful reagents for treating
      PC. We previously constructed a CRCA, cancer terminator virus (CTV), which showed
      efficacy both in vitro and in vivo for PC. The CTV was generated on a serotype 5
      background (Ad.5-CTV) with infectivity depending on Coxsackie-Adenovirus
      Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs
      thereby limiting effective Ad-mediated therapy. Using serotype chimerism, a novel
      CTV (Ad.5/3-CTV) was created by replacing the Ad.5 fiber knob with the Ad.3 fiber
      knob thereby facilitating infection in a CAR-independent manner. We evaluated
      Ad.5/3-CTV in comparison with Ad.5-CTV in low CAR human PC cells, demonstrating
      higher efficiency in inhibiting cell viability in vitro. Moreover, Ad.5/3-CTV
      potently suppressed in vivo tumor growth in a nude mouse xenograft model and in a
      spontaneously induced PC that develops in Hi-myc transgenic mice. Considering the
      significant responses in a Phase I clinical trial of a non-replicating Ad.5-mda-7
      in advanced cancers, Ad.5/3-CTV may exert improved therapeutic benefit in a
      clinical setting.

PMID- 23868770
TI  - A framework for binding and retrieving class-specific information to and from
      image patterns using correlation filters.
AB  - We describe a template-based framework to bind class-specific information to a
      set of image patterns and retrieve that information by matching the template to a
      query pattern of the same class. This is done by mapping the class-specific
      information to a set of spatial translations which are applied to the set of
      image patterns from which a template is designed, taking advantage of the
      properties of correlation filters. The bound information is retrieved during
      matching with an authentic query by estimating the spatial translations applied
      to the images that were used to design the template. In this paper, we focus on
      the problem of binding information to biometric signatures as an application of
      our framework. Our framework is flexible enough to allow spreading the
      information to be bound over multiple pattern classes which, in the context of
      biometric key-binding, enables multiclass and multimodal biometric key-binding.
      We demonstrate the effectiveness of the proposed scheme via extensive numerical
      results on multiple biometric databases. 

PMID- 23868771
TI  - A rank-based approach to active diagnosis.
AB  - The problem of active diagnosis arises in several applications such as disease
      diagnosis and fault diagnosis in computer networks, where the goal is to rapidly
      identify the binary states of a set of objects (e.g., faulty or working) by
      sequentially selecting, and observing, potentially noisy responses to binary
      valued queries. Previous work in this area chooses queries sequentially based on
      Information gain, and the object states are inferred by maximum a posteriori
      (MAP) estimation. In this work, rather than MAP estimation, we aim to rank
      objects according to their posterior fault probability. We propose a greedy
      algorithm to choose queries sequentially by maximizing the area under the ROC
      curve associated with the ranked list. The proposed algorithm overcomes
      limitations of existing work. When multiple faults may be present, the proposed
      algorithm does not rely on belief propagation, making it feasible for large scale
      networks with little loss in performance. When a single fault is present, the
      proposed algorithm can be implemented without knowledge of the underlying query
      noise distribution, making it robust to any misspecification of these noise
      parameters. We demonstrate the performance of the proposed algorithm through
      experiments on computer networks, a toxic chemical database, and synthetic
      datasets. 

PMID- 23868772
TI  - Calibration of smooth camera models.
AB  - Generic imaging models can be used to represent any camera. Current generic
      models are discrete and define a mapping between each pixel in the image and a
      straight line in 3D space. This paper presents a modification of the generic
      camera model that allows the simplification of the calibration procedure. The
      only requirement is that the coordinates of the 3D projecting lines are related
      by functions that vary smoothly across space. Such a model is obtained by
      modifying the general imaging model using radial basis functions (RBFs) to
      interpolate image coordinates and 3D lines, thereby allowing both an increase in
      resolution (due to their continuous nature) and a more compact representation.
      Using this variation of the general imaging model, we also develop a calibration
      procedure. This procedure only requires that a 3D point be matched to each pixel.
      In addition, not all the pixels need to be calibrated. As a result, the
      complexity of the procedure is significantly decreased. Normalization is applied
      to the coordinates of both image and 3D points, which increases the accuracy of
      the calibration. Results with both synthetic and real datasets show that the
      model and calibration procedure are easily applicable and provide accurate
      calibration results. 

PMID- 23868773
TI  - Efficient methods for overlapping group lasso.
AB  - The group Lasso is an extension of the Lasso for feature selection on
      (predefined) nonoverlapping groups of features. The nonoverlapping group
      structure limits its applicability in practice. There have been several recent
      attempts to study a more general formulation where groups of features are given,
      potentially with overlaps between the groups. The resulting optimization is,
      however, much more challenging to solve due to the group overlaps. In this paper,
      we consider the efficient optimization of the overlapping group Lasso penalized
      problem. We reveal several key properties of the proximal operator associated
      with the overlapping group Lasso, and compute the proximal operator by solving
      the smooth and convex dual problem, which allows the use of the gradient descent
      type of algorithms for the optimization. Our methods and theoretical results are
      then generalized to tackle the general overlapping group Lasso formulation based
      on the l(q) norm. We further extend our algorithm to solve a nonconvex
      overlapping group Lasso formulation based on the capped norm regularization,
      which reduces the estimation bias introduced by the convex penalty. We have
      performed empirical evaluations using both a synthetic and the breast cancer gene
      expression dataset, which consists of 8,141 genes organized into (overlapping)
      gene sets. Experimental results show that the proposed algorithm is more
      efficient than existing state-of-the-art algorithms. Results also demonstrate the
      effectiveness of the nonconvex formulation for overlapping group Lasso.

PMID- 23868774
TI  - Fast and accurate matrix completion via truncated nuclear norm regularization.
AB  - Recovering a large matrix from a small subset of its entries is a challenging
      problem arising in many real applications, such as image inpainting and
      recommender systems. Many existing approaches formulate this problem as a general
      low-rank matrix approximation problem. Since the rank operator is nonconvex and
      discontinuous, most of the recent theoretical studies use the nuclear norm as a
      convex relaxation. One major limitation of the existing approaches based on
      nuclear norm minimization is that all the singular values are simultaneously
      minimized, and thus the rank may not be well approximated in practice. In this
      paper, we propose to achieve a better approximation to the rank of matrix by
      truncated nuclear norm, which is given by the nuclear norm subtracted by the sum
      of the largest few singular values. In addition, we develop a novel matrix
      completion algorithm by minimizing the Truncated Nuclear Norm. We further develop
      three efficient iterative procedures, TNNR-ADMM, TNNR-APGL, and TNNR-ADMMAP, to
      solve the optimization problem. TNNR-ADMM utilizes the alternating direction
      method of multipliers (ADMM), while TNNR-AGPL applies the accelerated proximal
      gradient line search method (APGL) for the final optimization. For TNNR-ADMMAP,
      we make use of an adaptive penalty according to a novel update rule for ADMM to
      achieve a faster convergence rate. Our empirical study shows encouraging results
      of the proposed algorithms in comparison to the state-of-the-art matrix
      completion algorithms on both synthetic and real visual datasets. 

PMID- 23868775
TI  - Fast detection of dense subgraphs with iterative shrinking and expansion.
AB  - In this paper, we propose an efficient algorithm to detect dense subgraphs of a
      weighted graph. The proposed algorithm, called the shrinking and expansion
      algorithm (SEA), iterates between two phases, namely, the expansion phase and the
      shrink phase, until convergence. For a current subgraph, the expansion phase adds
      the most related vertices based on the average affinity between each vertex and
      the subgraph. The shrink phase considers all pairwise relations in the current
      subgraph and filters out vertices whose average affinities to other vertices are
      smaller than the average affinity of the result subgraph. In both phases, SEA
      operates on small subgraphs; thus it is very efficient. Significant dense
      subgraphs are robustly enumerated by running SEA from each vertex of the graph.
      We evaluate SEA on two different applications: solving correspondence problems
      and cluster analysis. Both theoretic analysis and experimental results show that
      SEA is very efficient and robust, especially when there exists a large amount of
      noise in edge weights. 

PMID- 23868776
TI  - FOCUSR: feature oriented correspondence using spectral regularization--a method
      for precise surface matching.
AB  - Existing methods for surface matching are limited by the tradeoff between
      precision and computational efficiency. Here, we present an improved algorithm
      for dense vertex-to-vertex correspondence that uses direct matching of features
      defined on a surface and improves it by using spectral correspondence as a
      regularization. This algorithm has the speed of both feature matching and
      spectral matching while exhibiting greatly improved precision (distance errors of
      1.4 percent). The method, FOCUSR, incorporates implicitly such additional
      features to calculate the correspondence and relies on the smoothness of the
      lowest-frequency harmonics of a graph Laplacian to spatially regularize the
      features. In its simplest form, FOCUSR is an improved spectral correspondence
      method that nonrigidly deforms spectral embeddings. We provide here a full
      realization of spectral correspondence where virtually any feature can be used as
      an additional information using weights on graph edges, but also on graph nodes
      and as extra embedded coordinates. As an example, the full power of FOCUSR is
      demonstrated in a real-case scenario with the challenging task of brain surface
      matching across several individuals. Our results show that combining features and
      regularizing them in a spectral embedding greatly improves the matching precision
      (to a submillimeter level) while performing at much greater speed than existing
      methods. 

PMID- 23868777
TI  - Jensen-Bregman LogDet divergence with application to efficient similarity search
      for covariance matrices.
AB  - Covariance matrices have found success in several computer vision applications,
      including activity recognition, visual surveillance, and diffusion tensor
      imaging. This is because they provide an easy platform for fusing multiple
      features compactly. An important task in all of these applications is to compare
      two covariance matrices using a (dis)similarity function, for which the common
      choice is the Riemannian metric on the manifold inhabited by these matrices. As
      this Riemannian manifold is not flat, the dissimilarities should take into
      account the curvature of the manifold. As a result, such distance computations
      tend to slow down, especially when the matrix dimensions are large or gradients
      are required. Further, suitability of the metric to enable efficient nearest
      neighbor retrieval is an important requirement in the contemporary times of big
      data analytics. To alleviate these difficulties, this paper proposes a novel
      dissimilarity measure for covariances, the Jensen-Bregman LogDet Divergence
      (JBLD). This divergence enjoys several desirable theoretical properties and at
      the same time is computationally less demanding (compared to standard measures).
      Utilizing the fact that the square root of JBLD is a metric, we address the
      problem of efficient nearest neighbor retrieval on large covariance datasets via
      a metric tree data structure. To this end, we propose a K-Means clustering
      algorithm on JBLD. We demonstrate the superior performance of JBLD on covariance
      datasets from several computer vision applications. 

PMID- 23868778
TI  - KNN Matting.
AB  - This paper proposes to apply the nonlocal principle to general alpha matting for
      the simultaneous extraction of multiple image layers; each layer may have
      disjoint as well as coherent segments typical of foreground mattes in natural
      image matting. The estimated alphas also satisfy the summation constraint. As in
      nonlocal matting, our approach does not assume the local color-line model and
      does not require sophisticated sampling or learning strategies. On the other
      hand, our matting method generalizes well to any color or feature space in any
      dimension, any number of alphas and layers at a pixel beyond two, and comes with
      an arguably simpler implementation, which we have made publicly available. Our
      matting technique, aptly called KNN matting, capitalizes on the nonlocal
      principle by using $(K)$ nearest neighbors (KNN) in matching nonlocal
      neighborhoods, and contributes a simple and fast algorithm that produces
      competitive results with sparse user markups. KNN matting has a closed-form
      solution that can leverage the preconditioned conjugate gradient method to
      produce an efficient implementation. Experimental evaluation on benchmark
      datasets indicates that our matting results are comparable to or of higher
      quality than state-of-the-art methods requiring more involved implementation. In
      this paper, we take the nonlocal principle beyond alpha estimation and extract
      overlapping image layers using the same Laplacian framework. Given the alpha
      value, our closed form solution can be elegantly generalized to solve the
      multilayer extraction problem. We perform qualitative and quantitative
      comparisons to demonstrate the accuracy of the extracted image layers. 

PMID- 23868779
TI  - Learning AND-OR templates for object recognition and detection.
AB  - This paper presents a framework for unsupervised learning of a hierarchical
      reconfigurable image template--the AND-OR Template (AOT) for visual objects. The
      AOT includes: 1) hierarchical composition as "AND" nodes, 2) deformation and
      articulation of parts as geometric "OR" nodes, and 3) multiple ways of
      composition as structural "OR" nodes. The terminal nodes are hybrid image
      templates (HIT) [17] that are fully generative to the pixels. We show that both
      the structures and parameters of the AOT model can be learned in an unsupervised
      way from images using an information projection principle. The learning algorithm
      consists of two steps: 1) a recursive block pursuit procedure to learn the
      hierarchical dictionary of primitives, parts, and objects, and 2) a graph
      compression procedure to minimize model structure for better generalizability. We
      investigate the factors that influence how well the learning algorithm can
      identify the underlying AOT. And we propose a number of ways to evaluate the
      performance of the learned AOTs through both synthesized examples and real-world
      images. Our model advances the state of the art for object detection by improving
      the accuracy of template matching. 

PMID- 23868780
TI  - Modeling natural images using gated MRFs.
AB  - This paper describes a Markov Random Field for real-valued image modeling that
      has two sets of latent variables. One set is used to gate the interactions
      between all pairs of pixels, while the second set determines the mean intensities
      of each pixel. This is a powerful model with a conditional distribution over the
      input that is Gaussian, with both mean and covariance determined by the
      configuration of latent variables, which is unlike previous models that were
      restricted to using Gaussians with either a fixed mean or a diagonal covariance
      matrix. Thanks to the increased flexibility, this gated MRF can generate more
      realistic samples after training on an unconstrained distribution of high
      resolution natural images. Furthermore, the latent variables of the model can be
      inferred efficiently and can be used as very effective descriptors in recognition
      tasks. Both generation and discrimination drastically improve as layers of binary
      latent variables are added to the model, yielding a hierarchical model called a
      Deep Belief Network. 

PMID- 23868782
TI  - Projective multiview structure and motion from element-wise factorization.
AB  - The Sturm-Triggs type iteration is a classic approach for solving the projective
      structure-from-motion (SfM) factorization problem, which iteratively solves the
      projective depths, scene structure, and camera motions in an alternated fashion.
      Like many other iterative algorithms, the Sturm-Triggs iteration suffers from
      common drawbacks, such as requiring a good initialization, the iteration may not
      converge or may only converge to a local minimum, and so on. In this paper, we
      formulate the projective SfM problem as a novel and original element-wise
      factorization (i.e., Hadamard factorization) problem, as opposed to the
      conventional matrix factorization. Thanks to this formulation, we are able to
      solve the projective depths, structure, and camera motions simultaneously by
      convex optimization. To address the scalability issue, we adopt a continuation
      based algorithm. Our method is a global method, in the sense that it is
      guaranteed to obtain a globally optimal solution up to relaxation gap. Another
      advantage is that our method can handle challenging real-world situations such as
      missing data and outliers quite easily, and all in a natural and unified manner.
      Extensive experiments on both synthetic and real images show comparable results
      compared with the state-of-the-art methods. 

PMID- 23868781
TI  - Multi-exemplar affinity propagation.
AB  - The affinity propagation (AP) clustering algorithm has received much attention in
      the past few years. AP is appealing because it is efficient, insensitive to
      initialization, and it produces clusters at a lower error rate than other
      exemplar-based methods. However, its single-exemplar model becomes inadequate
      when applied to model multisubclasses in some situations such as scene analysis
      and character recognition. To remedy this deficiency, we have extended the single
      exemplar model to a multi-exemplar one to create a new multi-exemplar affinity
      propagation (MEAP) algorithm. This new model automatically determines the number
      of exemplars in each cluster associated with a super exemplar to approximate the
      subclasses in the category. Solving the model is NP-hard and we tackle it with
      the max-sum belief propagation to produce neighborhood maximum clusters, with no
      need to specify beforehand the number of clusters, multi-exemplars, and
      superexemplars. Also, utilizing the sparsity in the data, we are able to reduce
      substantially the computational time and storage. Experimental studies have shown
      MEAP's significant improvements over other algorithms on unsupervised image
      categorization and the clustering of handwritten digits.

PMID- 23868783
TI  - Range image registration using a photometric metric under unknown lighting.
AB  - Based on the spherical harmonics representation of image formation, we derive a
      new photometric metric for evaluating the correctness of a given rigid
      transformation aligning two overlapping range images captured under unknown,
      distant, and general illumination. We estimate the surrounding illumination and
      albedo values of points of the two range images from the point correspondences
      induced by the input transformation. We then synthesize the color of both range
      images using albedo values transferred using the point correspondences to compute
      the photometric reprojection error. This way allows us to accurately register two
      range images by finding the transformation that minimizes the photometric
      reprojection error. We also propose a practical method using the proposed
      photometric metric to register pairs of range images devoid of salient geometric
      features, captured under unknown lighting. Our method uses a hypothesize-and-test
      strategy to search for the transformation that minimizes our photometric metric.
      Transformation candidates are efficiently generated by employing the spherical
      representation of each range image. Experimental results using both synthetic and
      real data demonstrate the usefulness of the proposed metric. 

PMID- 23868784
TI  - 3D face recognition under expressions, occlusions, and pose variations.
AB  - We propose a novel geometric framework for analyzing 3D faces, with the specific
      goals of comparing, matching, and averaging their shapes. Here we represent
      facial surfaces by radial curves emanating from the nose tips and use elastic
      shape analysis of these curves to develop a Riemannian framework for analyzing
      shapes of full facial surfaces. This representation, along with the elastic
      Riemannian metric, seems natural for measuring facial deformations and is robust
      to challenges such as large facial expressions (especially those with open
      mouths), large pose variations, missing parts, and partial occlusions due to
      glasses, hair, and so on. This framework is shown to be promising from both-
      empirical and theoretical--perspectives. In terms of the empirical evaluation,
      our results match or improve upon the state-of-the-art methods on three prominent
      databases: FRGCv2, GavabDB, and Bosphorus, each posing a different type of
      challenge. From a theoretical perspective, this framework allows for formal
      statistical inferences, such as the estimation of missing facial parts using PCA
      on tangent spaces and computing average shapes.

PMID- 23868786
TI  - Symmetric fast marching schemes for better numerical isotropy.
AB  - Existing fast marching methods solve the Eikonal equation using a continuous
      (first-order) model to estimate the accumulated cost, but a discontinuous (zero
      order) model for the traveling cost at each grid point. As a result the estimate
      of the accumulated cost (calculated numerically) at a given point will vary based
      on the direction of the arriving front, introducing an anisotropy into the
      discrete algorithm even though the continuous partial differential equation (PDE)
      is itself isotropic. To remove this anisotropy, we propose two very different
      schemes. In the first model, we utilize a continuous interpolation of the
      traveling cost, which is not biased by the direction of the propagating front. In
      the second model, we upsample the traveling cost on a higher resolution grid to
      overcome the directional bias. We show the significance of removing the
      directional bias in the computation of the cost in some applications of the fast
      marching method, demonstrating that both methods make the discrete implementation
      more isotropic, in accordance with the underlying continuous PDE. 

PMID- 23868785
TI  - WESD--Weighted Spectral Distance for measuring shape dissimilarity.
AB  - This paper presents a new distance for measuring shape dissimilarity between
      objects. Recent publications introduced the use of eigenvalues of the Laplace
      operator as compact shape descriptors. Here, we revisit the eigenvalues to define
      a proper distance, called Weighted Spectral Distance (WESD), for quantifying
      shape dissimilarity. The definition of WESD is derived through analyzing the heat
      trace. This analysis provides the proposed distance with an intuitive meaning and
      mathematically links it to the intrinsic geometry of objects. We analyze the
      resulting distance definition, present and prove its important theoretical
      properties. Some of these properties include: 1) WESD is defined over the entire
      sequence of eigenvalues yet it is guaranteed to converge, 2) it is a
      pseudometric, 3) it is accurately approximated with a finite number of
      eigenvalues, and 4) it can be mapped to the [0,1) interval. Last, experiments
      conducted on synthetic and real objects are presented. These experiments
      highlight the practical benefits of WESD for applications in vision and medical
      image analysis.

PMID- 23868787
TI  - A class of random fields on complete graphs with tractable partition function.
AB  - The aim of this short note is to draw attention to a method by which the
      partition function and marginal probabilities for a certain class of random
      fields on complete graphs can be computed in polynomial time. This class includes
      Ising models with homogeneous pairwise potentials but arbitrary (inhomogeneous)
      unary potentials. Similarly, the partition function and marginal probabilities
      can be computed in polynomial time for random fields on complete bipartite
      graphs, provided they have homogeneous pairwise potentials. We expect that these
      tractable classes of large-scale random fields can be very useful for the
      evaluation of approximation algorithms by providing exact error estimates. 

PMID- 23868788
TI  - Detection of unusual G6 rotavirus strains in Italian children with diarrhoea
      during the 2011 surveillance season.
AB  - Two rare G6 rotavirus A (RVA) strains, designated as RVA/human
      wt/ITA/CEC06/2011/G6P[6] and RVA/human-wt/ITA/PG05/2011/G6P[9], were identified
      in stool specimens from children hospitalized in Central Italy. After PCR
      genotyping, the samples CEC06 and PG05 gave G-UD-P[6] and G-UD-P[9] genotypes,
      respectively. To determine the G-type and to characterize further the two
      strains, sequencing of 8 of the 11 genomic segments was performed. CEC06 and PG05
      strains were found to possess unusual genotype constellations: G6-P[6]-I2-A2-N2
      T2-E2-H2 and G6-P[9]-I2-A3-N2-T3-E3-H3, respectively. This study reports the
      first detection of rare G6P[6] and G6P[9] RVA strains in peninsular Italy.
      Phylogenetic analysis of VP4 (VP8*), VP7, VP6, and NSP1-5 showed no evidence of
      zoonosis or inter-species reassortment, revealing for both strains constellations
      previously associated to human cases.

PMID- 23868789
TI  - Testosterone boosts for treatment of castration resistant prostate cancer: an
      experimental implementation of intermittent androgen deprivation.
AB  - BACKGROUND: The primary therapeutic target for non-organ-confined prostate cancer
      is the androgen receptor (AR). Main strategies to ablate AR function are androgen
      depletion and direct receptor blockade by AR antagonists. However, incurable
      castration resistant prostate cancer (CRPC) develops resistance mechanisms to
      cope with trace amounts of androgen including AR overexpression and mutation in
      the AR ligand binding domain. METHODS: The CRPC cell model VCaP derivative of a
      prostate cancer bone metastasis was used in vitro and in nude mice in vivo to
      examine the effects of immediate testosterone boost on CRPC cells. In addition, a
      testosterone tolerant cell model was established by incremental acclimatization
      of VCaP cells to 1 nM testosterone. The effects of androgen withdrawal and
      testosterone boosts on gene expression were assessed by quantitative real-time
      polymerase chain reaction, ELISA, and Western blots. Tumor cell proliferation was
      evaluated with a BrdU test. RESULTS: Testosterone boosts on CRPC VCaP cells
      eliminate tumor cells to a higher extent than androgen withdrawal in androgen
      tolerant cells. The pronounced decrease of tumor cell proliferation was
      accompanied by a marked downregulation of AR expression regarding full-length AR
      and splice variant AR V7. CONCLUSIONS: Acquiring castration resistance of
      prostate cancer cells by AR overexpression and amplification obviously sensitizes
      such cells to testosterone concentrations as low as physiological values. This
      introduces novel therapeutic means to treat CRPC with non-toxic measures and may
      find clinical implementation in intermittent androgen deprivation regimens.

PMID- 23868790
TI  - C-H alkenylation of azoles with enols and esters by nickel catalysis.
AB  - Rather u(Ni)que: Two new C-H alkenylation reactions, that is C-H/C-O alkenylation
      and decarbonylative C-H alkenylation, of azoles are uniquely catalyzed by
      Ni/dcype. These azole alkenylation reactions are successfully applied to the
      convergent formal synthesis of siphonazole B.

PMID- 23868791
TI  - Line patterns from cylinder-forming photocleavable block copolymers.
AB  - A robust route for the preparation of nanoscopic line patterns from polystyrene
      block-poly(ethylene oxide) featuring a photocleavable o-nitrobenzyl ester
      junction is demonstrated. After mild UV (lambda = 365 nm) exposure and selective
      removal of the PEO microdomains, the polymer trench patterns are used as scaffold
      to fabricate highly ordered arrays of silica or Au line patterns. 

PMID- 23868792
TI  - Characteristics of older patients with back pain in general practice: BACE cohort
      study.
AB  - BACKGROUND: Although back pain is common among older people, limited information
      is available about the characteristics of these patients in primary care. Earlier
      research suggests that the severity of back symptoms increases with older age.
      METHODS: Patients aged >55 years visiting a general practitioner with a new
      episode of back pain were included in the BACE study. Information on patients'
      characteristics, characteristics of the complaint and physical examination were
      derived from the baseline measurement. Cross-sectional differences between
      patients aged >55-74 and >=75 years were analysed using an unpaired t-test, Mann
      Whitney U-test or a chi-square test. RESULTS: A total of 675 back pain patients
      were included in the BACE study, with a median age of 65 (interquartile range 60
      71) years. Patients aged >55-74 years had a mean disability score (measured with
      the Roland Disability Questionnaire) of 9.4 [standard deviation (SD) 5.8]
      compared with 12.1 (SD 5.5) in patients aged >=75 years (p <= 0.01). The older
      group reported more additional musculoskeletal disorders and more often had low
      bone quality (based on ultrasound measurement of the heel) than patients aged >55
      74 years. Average back pain severity over the previous week showed no difference
      (p = 0.11) between the age groups, but severity of back pain at the moment of
      filling in the questionnaire was higher (p = 0.03) in the older age group.
      CONCLUSIONS: In this study, older back pain patients reported more disabilities
      and co-morbidity. However, the clinical relevance of these differences for the
      course of the back pain episode in older patients remains a subject for further
      research.

PMID- 23868793
TI  - Prevalence of 25-hydroxyvitamin D deficiency in child and adolescent patients
      undergoing hematopoietic cell transplantation compared to a healthy population.
AB  - BACKGROUND: Pediatric patients undergoing allogeneic hematopoietic cell
      transplant (HCT) are at risk for low bone mineral density, which may due, in
      part, to low 25-hydroxyvitamin D levels. PROCEDURE: We compared the serum 25
      hydroxyvitamin D status of 22 pediatric HCT patients with 100 healthy pediatric
      controls. We determined the prevalence of and risk factors for 25-hydroxyvitamin
      D insufficiency and deficiency. RESULTS: Serum 25-hydroxyvitamin D levels were
      lower in the pediatric HCT patients at time of transplant than healthy pediatric
      controls (median 19.5 ng/ml vs. 31.0 ng/ml, P < 0.001). Of HCT patients, 27% were
      25-hydroxyvitamin D deficient (<15 ng/dl) and 68% insufficient (15-29 ng/dl),
      compared with 4% and 40%, respectively, of healthy pediatric controls (P <
      0.001). In multivariable analysis, treatment with HCT, decreased ambient
      ultraviolet light exposure, non-Caucasian race, and older age were associated
      with decreased serum 25-hydroxyvitamin D levels. No association was found between
      25-hydroxyvitamin D levels and gender, body mass index, dietary vitamin D intake,
      or patient-reported vitamin D supplementation. Few patients in either group
      reported sunscreen use, vitamin D supplementation, or recommended dietary vitamin
      D intake. CONCLUSIONS: At time of transplant, pediatric HCT patients frequently
      have 25-hydroxyvitamin D insufficiency/deficiency, and this occurs more commonly
      than in the healthy pediatric population. HCT patients rarely follow recommended
      guidelines to take supplemental vitamin D, consume the Recommended Daily
      Allowance for vitamin D, or regularly use sunscreen. Further studies are needed
      to determine whether vitamin D insufficiency/deficiency persists long term in HCT
      patients and requires dietary and behavioral interventions.

PMID- 23868794
TI  - OnabotulinumtoxinA injection therapy in men with LUTS due to primary bladder-neck
      dysfunction: objective and patient-reported outcomes.
AB  - OBJECTIVE: To determine efficacy and safety of OnabotulinumtoxinA (BoNT-A)
      injection therapy in medically refractory patients with lower urinary tract
      symptoms (LUTS) due to primary bladder-neck dysfunction (PBND). MATERIALS AND
      METHODS: Thirty-five consecutive ambulatory males diagnosed with PBND and
      refractory to medical therapy, with IPSS > 15, Qmax < 15 ml/sec, and total
      prostate volume < 30 cm(3), were screened from January 2010 to December 2011.
      Eligible patients underwent transurethral bladder-neck injection of BoNT-A (200
      U, 50 U/ml * 4 sites) and were assessed at baseline, 2-, 6-, 9-, and 12-month
      postprocedure and until duration of clinical response. The primary outcome was
      the change from baseline in total IPSS, and secondary outcome were storage- and
      voiding-IPSS, QoL score, Qmax, and postvoiding residual volume (PVR), patient
      reported outcomes. Adverse effects were also recorded, including ejaculatory
      dysfunctions. RESULTS: Of 30 enrolled patients (mean age 33.8 years), 29 (96.7%)
      completed the study. A statistically significant improvement of total IPSS was
      observed from 21.9 at baseline, to 7.8, 10.3, and 16.6 at 2, 6, and 9 months,
      respectively (P < 0.000). Statistically significant improvements from baseline of
      storage- and voiding-IPSS, QoL score, Qmax, and PVR were also observed until 9
      month postprocedure. The proportion of patients with overall satisfaction was
      favorable although decreasing from 80% at 2 months, to 44.8% at 12 months. No
      significant adverse effects or ejaculatory dysfunctions were noted. CONCLUSIONS:
      BoNT-A injection therapy appears effective and safe in medically refractory men
      with PBND, although repeated procedures are required for long-term sustained
      benefit. Randomized controlled trials are warranted in order to corroborate these
      results.

PMID- 23868799
TI  - Phenolic distribution in liquid preparations of Vaccinium myrtillus L. and
      Vaccinium vitis idaea L.
AB  - INTRODUCTION: Liquid preparations such as tinctures and 'bud extracts' of
      bilberry and lingonberry are typical products used in some European countries but
      they have not been widely studied to date. OBJECTIVE: Our aim was to define a
      phytochemical profile in terms of phenolic compounds for liquid preparations of
      Vaccinium myrtillus L. (bilberry) and Vaccinium vitis idaea L. (lingonberry)
      foliar tissues, and evaluate their stability. METHODS: Up to 17 extracts of
      lingonberry, and bilberry have been analysed by HPLC equipped with a diode-array
      detector (DAD) in combination with MS. Some of these samples were freshly
      prepared (laboratory extracts). RESULTS: Phenolic profiles of the bud extracts
      and tinctures of bilberry and lingonberry were obtained at 330 nm, typical of the
      cinnamoyl compounds and suitable to distinguish these two species. Analogously,
      the profiles at 280 nm were used to detect the arbutin derivatives recognised as
      the typical markers of lingonberry leaves only. Among the cinnamoyl derivatives,
      chlorogenic acid was the main compound found in bilberry samples, while caffeoyl
      arbutin was the principal marker in lingonberry samples. In quantitative terms,
      the hydroxycinnamic acids were the main class in bilberry bud extracts ranging
      between 4.67 and 6.81 mg/L (from 52 to 84% of the total phenols). The young
      sprouts of this species, independently from the extraction mixture, show a higher
      phenolic content than adult leaves of the same plant. CONCLUSIONS: The analytical
      method allowed to define fingerprints of bilberry and lingonberry liquid
      preparations. Moreover, without applying accelerated ageing protocols, the
      stability over time of 11 samples was evaluated up to 6 months, demonstrating
      negligible variations.

PMID- 23868804
TI  - Transcription factor Sp1 regulates T-type Ca(2+) channel CaV 3.1 gene expression.
AB  - Voltage-gated T-type Ca(2+) (CaV 3) channels mediate a number of physiological
      events in developing and mature cells, and are implicated in neurological and
      cardiovascular diseases. In mammals, there are three distinct T-channel genes
      (CACNA1G, CACNA1H, and CACNA1I) encoding proteins (CaV 3.1-CaV 3.3) that differ
      in their localization as well as in molecular, biophysical, and pharmacological
      properties. The CACNA1G is a large gene that contains 38 exons and is localized
      in chromosome 17q22. Only basic characteristics of the CACNA1G gene promoter
      region have been investigated classifying it as a TATA-less sequence containing
      several potential transcription factor-binding motifs. Here, we cloned and
      characterized a proximal promoter region and initiated the analysis of
      transcription factors that control CaV 3.1 channel expression using the murine
      Cacna1g gene as a model. We isolated a ~1.5 kb 5'-upstream region of Cacna1g and
      verified its transcriptional activity in the mouse neuroblastoma N1E-115 cell
      line. In silico analysis revealed that this region possesses a TATA-less minimal
      promoter that includes two potential transcription start sites and four binding
      sites for the transcription factor Sp1. The ability of one of these sites to
      interact with the transcription factor was confirmed by electrophoretic mobility
      shift assays. Consistent with this, Sp1 over-expression enhanced promoter
      activity while siRNA-mediated Sp1 silencing significantly decreased the level of
      CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents
      expressed in the N1E-115 cells. These results provide new insights into the
      molecular mechanisms that control CaV 3.1 channel expression.

PMID- 23868805
TI  - Whiter, brighter, and more stable cellulose paper coated with TiO2 /SiO2
      core/shell nanoparticles using a layer-by-layer approach.
AB  - To inhibit the photocatalytic degradation of organic material supports induced by
      small titania (TiO2 ) nanoparticles, four kinds of TiO2 nanoparticles, that is,
      commercial P25-TiO2 , commercial rutile phase TiO2 , rutile TiO2 nanorods and
      rutile TiO2 spheres, prepared from TiCl4 , were coated with a thin, but dense,
      coating of silica (SiO2 ) using a conventional sol-gel technique to form TiO2
      /SiO2 core/shell nanoparticles. These core/shell particles were deposited and
      fixed as a very thin coating onto the surface of cellulose paper samples by a wet
      chemistry polyelectrolyte layer-by-layer approach. The TiO2 /SiO2 nanocoated
      paper samples exhibit higher whiteness and brightness and greater stability to UV
      bleaching than comparable samples of blank paper. There are many potential
      applications for this green chemistry approach to protect cellulosic fibres from
      UV-bleaching in sunlight and to improve their whiteness and brightness. 

PMID- 23868806
TI  - Copper-catalyzed tandem trifluoromethylation/semipinacol rearrangement of allylic
      alcohols.

PMID- 23868807
TI  - Phenylbutyrate increases activity of pyruvate dehydrogenase complex.

PMID- 23868808
TI  - Genetically engineered peptides for inorganics: study of an unconstrained
      bacterial display technology and bulk aluminum alloy.
AB  - The first-ever peptide biomaterial discovery using an unconstrained engineered
      bacterial display technology is reported. Using this approach, we have developed
      genetically engineered peptide binders for a bulk aluminum alloy and use
      molecular dynamics simulation of peptide conformational fluctuations to
      demonstrate sequence-dependent, structure-function relationships for metal and
      metal oxide interactions. 

PMID- 23868809
TI  - Epidemiological distribution and genotype characterization of hepatitis C virus
      and HIV co-infection in Wuhan, China, where the prevalence of HIV is low.
AB  - Little is known about the epidemiological characteristics of HIV/hepatitis C
      virus (HCV) co-infection in cities in China with low HIV prevalence. This study
      evaluated the level of exposure to different risk factors associated with HCV
      transmission and characterized the distribution of HCV genotypes in 356 HIV-1
      positive patients in Wuhan, central China. HIV transmission routes were
      distributed as follows: heterosexual contact, male-to-male sexual contact,
      intravenous drug use, blood transfusion, and unknown route. HCV antibodies were
      detected by a third-generation enzyme-linked immunosorbent assay. HCV-positive
      plasmas were subjected to RNA extraction, RT-PCR amplification, and sequencing.
      Phylogenetic analysis characterized HCV subtypes and the evolutionary origin of
      circulating HCV strains. Ninety-two of 356 (25.8%) patients infected with HIV
      were anti-HCV-positive. Among co-infected patients, the predominant risk for HCV
      transmission was intravenous drug use (87.3%). Six HCV subtypes (1a, 1b, 2a, 3a,
      3b, and 6a) were detected. HCV genotype 6a was most prevalent, occurring in 39.3%
      of all patients, followed by genotypes 1b (24.7%), 3b (18.0%), and 3a (9.8%). The
      least frequent genotypes were 1a (4.9%) and 2a (3.3%). Intravenous drug use was
      strongly associated with genotype 6a, and infection by blood or blood product
      transfusion was strongly associated with genotype 1b. Genotype 2a was detected
      only among those infected by male-to-male sexual contact. The distribution of HCV
      subtypes suggests that the city plays a crucial role as a hub of HCV transmission
      in China. Exposure to multiple risk factors associated with HCV transmission was
      common among patients co-infected with HIV and HCV.

PMID- 23868810
TI  - Tropisetron alleviate early post-operative pain after gynecological laparoscopy
      in sevoflurane based general anaesthesia: a randomized, parallel-group, factorial
      study.
AB  - BACKGROUND: Studies have suggested that 5-hydroxytryptamine-3A (5-HT-3A) receptor
      antagonists may have analgesic effects. This randomized, double-blind, placebo
      controlled, factorial study tested the hypothesis that 5-HT-3A receptor
      antagonist tropisetron attenuates post-operative pain in women receiving either
      sevoflurane or propofol based anaesthesia. METHODS: Two hundred and ninety-six
      women undergoing gynaecological laparoscopies were randomly assigned to be
      anaesthetized with either sevoflurane or propofol. Immediately after the
      induction of anaesthesia, the anaesthesiologist administered either tropisetron 2
      mg or a placebo intravenously. Pain score at rest at 0.5 h post-operatively
      reported using a numerical rating scale was the primary outcome measure. The
      secondary outcome measures included pain score at rest every 2 h within the first
      24 h post-operatively, duration of post-anaesthesia care unit stay, incidence of
      post-operative nausea and vomiting, the incidence of shivering and score of the
      Quality of Recovery Score 40. RESULTS: Compared with placebo, tropisetron
      produced a statistically significant decrease on pain report within the first 6 h
      post-operatively in the sevoflurane-based anaesthesia group (3 [2, 4] vs. 5 [4,
      5], p < 0.001 in 0.5 h; 2 [0, 4] vs. 3 [3, 5], p < 0.001 in 2 h; 2 [0, 3] vs. 3
      [1, 4], p = 0.002 in 4 h; 1 [0, 3] vs. 2 [1, 4], p = 0.016 in 6 h), but not in
      the propofol-based group. CONCLUSIONS: A single-dose intravenous administration
      of tropisetron after anaesthesia induction is associated with statistically
      significant decreased early post-operative pain in patients undergoing
      gynaecological laparoscopies under sevoflurane based general anaesthesia.

PMID- 23868811
TI  - A comparison of central lines in pediatric oncology patients: Early removal and
      patient centered outcomes.
AB  - BACKGROUND: While there is increasing evidence supporting the choice of
      subcutaneous ports (SPs) over external venous catheters (EVCs) in pediatric
      oncology patients, prior conflicting studies exist and little data have been
      gathered as to which type of central line is preferred from the patient/family
      perspective. PROCEDURE: We performed a single institution, 10 years,
      retrospective analysis of central lines in pediatric oncology patients (n = 878)
      to evaluate unplanned early removal and cause of removal while simultaneously
      obtaining a cross sectional survey of 143 of the primary caretakers/parents of
      these patients to evaluate their overall satisfaction with the line. RESULTS:
      EVCs have significantly higher odds of unplanned early removal in comparison to
      SPs (6.7% of SPs vs. 27.3% of EVCs, odds ratio (OR) = 6.3, P < 0.0001 when
      controlling for age and diagnosis) secondary to increased infection, malfunction
      and patient preference. Patients with SPs felt like their central line was easier
      to care for, had less daily impact in their life, and were overall more satisfied
      with their central line compared to patients with EVCs, even when controlling for
      early removal (P < 0.0001 for all). SP patients were much more likely to state
      that they would choose the same type of line again (OR = 15, P < 0.0001) than EVC
      patients. CONCLUSION: SPs demonstrated lower removal rates and greater patient
      satisfaction than EVCs. These data should be considered when choosing a central
      line for pediatric cancer patients.

PMID- 23868812
TI  - Developing a tissue engineered repair material for treatment of stress urinary
      incontinence and pelvic organ prolapse-which cell source?
AB  - AIMS: Synthetic non-absorbable meshes are widely used to augment surgical repair
      of stress urinary incontinence (SUI) and pelvic organ prolapse (POP); however,
      there is growing concern such meshes are associated with serious complications.
      This study compares the potential of two autologous cell sources for attachment
      and extra-cellular matrix (ECM) production on a biodegradable scaffold to develop
      tissue engineered repair material (TERM). METHODS: Human oral fibroblasts (OF)
      and human adipose-derived stem cells (ADSC) were isolated and cultured on thermo
      annealed poly-L-lactic acid (PLA) scaffolds for two weeks under either
      unrestrained conditions or restrained (either with or without intermittent
      stress) conditions. Samples were tested for cell metabolic activity
      (AlamarBlue(r) assay), contraction (serial photographs analyzed with image J
      software), total collagen production (Sirius red assay), and production of ECM
      components (immunostaining for collagen I, III, and elastin; and scanning
      electron microscopy) and biomechanical properties (BOSE tensiometer). Differences
      were statistically tested using two sample t-test. RESULTS: Both cells showed
      good attachment and proliferation on scaffolds. Unrestrained scaffolds with ADSC
      produced more total collagen and a denser homogenous ECM than OF under same
      conditions. Restrained conditions (both with and without intermittent stress)
      gave similar total collagen production, but improved elastin production for both
      cells, particularly OF. The addition of any cell onto scaffolds led to an
      increase in biomechanical properties of scaffolds compared to unseeded scaffolds.
      CONCLUSIONS: OF and ADSC both appear to be suitable cell types to combine with
      biodegradable scaffolds, in the development of a TERM for the treatment of SUI
      and POP. Neurourol. Urodynam. 33:531-537, 2014. (c) 2013 Wiley Periodicals, Inc.

PMID- 23868813
TI  - Musculoskeletal pain among healthcare workers: an exploratory study on gender
      differences.
AB  - BACKGROUND: Musculoskeletal disorder rates among healthcare workers are high
      compared to other occupational groups. Studies indicate a higher prevalence of
      musculoskeletal pain in women as compared to men in most productive sectors. The
      objectives of our study were to assess the prevalence of upper-limb
      musculoskeletal pain in male and female employees of the Belo Horizonte municipal
      Health Department, and to identify associated factors, considering individual and
      occupational characteristics, by gender. METHODS: This cross-sectional study of a
      proportional sample of 1,721 subjects from a universe of 13,602 workers in the
      municipal health system evaluated the prevalence of self-reported upper-limb
      musculoskeletal pain. The magnitude of the associations was estimated by Poisson
      regression. RESULTS: The prevalence of upper-limb musculoskeletal pain was 24.1%
      among women and 11.0% among men. Women who had high domestic workloads, and
      performed tasks under high strain showed high prevalence of musculoskeletal pain.
      For women and men, a high prevalence of upper-limb pain was reported by those who
      performed highly physically demanding tasks, and those exposed to poor
      environmental conditions. CONCLUSIONS: The findings suggest gender differences in
      the distribution of upper-limb musculoskeletal pain across occupational groups.
      It also support initiatives that focus on the need to give visibility to the
      different effects of working conditions on the health of occupational groups and
      suggest the importance of developing specific measures to promote women's health.
      The higher prevalence of pain observed among women with high domestic workloads
      suggests the importance of these activities when evaluating workload in
      occupational studies.

PMID- 23868815
TI  - Lanthanide-doped upconverting nanoparticles: harvesting light for solar cells.

PMID- 23868814
TI  - How feasible is expectant management of interstitial ectopic pregnancy?
AB  - OBJECTIVE: To review the success rate of expectant management in a series of
      interstitial pregnancies. METHODS: We identified all women with an ultrasound
      diagnosis of interstitial pregnancy seen within a 9-year period (January 2004 to
      April 2013). The clinical history, ultrasound findings and biochemical results
      were reviewed. The outcome of all interstitial pregnancies managed conservatively
      was recorded. Treatment was considered as successful when the serum beta-human
      chorionic gonadotropin (beta-hCG) level declined below 20 IU/L without the need
      for further intervention. RESULTS: A total of 48 interstitial pregnancies were
      diagnosed during the study period. Surgery was the first-line treatment in nine
      (18.8%) cases. Thirty-eight (79.2%) women were offered non-surgical management:
      19 (39.6%) had methotrexate (MTX) and 19 (39.6%) were managed expectantly. One
      (2.1%) woman returned to her local hospital following diagnosis and we were
      unable to obtain any follow-up information regarding her care. The median initial
      serum beta-hCG level and ectopic size were not significantly different between
      any of the groups according to initial treatment. The overall success rate of
      expectant management was 89.5%. There were no cases of ectopic rupture in this
      group. Length of follow-up ranged from 7 to 141 days with a median duration of
      follow-up of 50.6 days. CONCLUSION: Our data show that expectant management is an
      option for selected women with non-viable interstitial pregnancies and declining
      serum beta-hCG levels, irrespective of ectopic mass size and initial serum beta
      hCG levels.

PMID- 23868816
TI  - Evaluation of the relationship between serum levels of VEGF and sVEGFR1 with
      mortality and prognosis in patients with Crimean-Congo hemorrhagic fever.
AB  - The most accepted view to explaining the pathogenesis of Crimean-Congo
      hemorrhagic fever (CCHF) is endothelial damage. This study was conducted in a
      University hospital to investigate the serum levels and prognostic significance
      of the vascular endothelial growth factor (VEGF) and its receptor, soluble fms
      like tyrosine kinase-1 receptor (sVEGFR-1) in CCHF. Forty-eight consecutive
      hospitalized CCHF patients (grouped into severe illness and non-severe illness)
      and 40 healthy adults, as controls were enrolled. There was statistically
      significant difference for each of VEGF (P = 0.003), and sVEGFR1 (P = 0.0001)
      between the patients and controls. VEGF and sVEGFR1 levels in patients with
      severe CCHF were found to be higher than in the control group (P = 0.0001 and P =
      0.0001, respectively). A significant difference was found in VEGF (P = 0.003) and
      sVEGFR1 (P = 0.0001) levels when compared to patients with CCHF who died and who
      recovered. In patients in the group with severe illness, the sensitivity,
      specificity, and the area underneath the ROC curve (AUROC) belonging to those cut
      off points of VEGF and sVEGFR1 were 66.7%, 76.2%, 0.747, and 77.8%, 81%, 0.849,
      respectively. In non-survivors, the sensitivity, specificity, and the AUROC
      belonging to those cut-off points of VEGF and sVEGFR1 defined as 77.8%, 76.9%,
      0.813, and 88.9%, 97.4%, 0.912, respectively. In conclusion, high sensitivity,
      specificity, and the AUROC values were found in sVEGFR1 levels especially in the
      severely ill and non-survivors. Therefore, sVEGFR1 may be an important biomarker
      for determining the risk of severity and death as result of infection with CCHF
      virus.

PMID- 23868817
TI  - Modeling the dispersion in electromechanically coupled myocardium.
AB  - We present an approach to model the dispersion of fiber and sheet orientations in
      the myocardium. By utilizing structure parameters, an existing orthotropic and
      invariant-based constitutive model developed to describe the passive behavior of
      the myocardium is augmented. Two dispersion parameters are fitted to
      experimentally observed angular dispersion data of the myocardial tissue.
      Computations are performed on a unit myocardium tissue cube and on a slice of the
      left ventricle indicating that the dispersion parameter has an effect on the
      myocardial deformation and stress development. The use of fiber dispersions
      relating to a pathological myocardium had a rather big effect. The final example
      represents an ellipsoidal model of the left ventricle indicating the influence of
      fiber and sheet dispersions upon contraction over a cardiac cycle. Although only
      a minor shift in the pressure-volume (PV) loops between the cases with no
      dispersions and with fiber and sheet dispersions for a healthy myocardium was
      observed, a remarkably different behavior is obtained with a fiber dispersion
      relating to a diseased myocardium. In future simulations, this dispersion model
      for myocardial tissue may advantageously be used together with models of, for
      example, growth and remodeling of various cardiac diseases.

PMID- 23868818
TI  - Assessing the quality of randomized controlled trials published in neurourology
      and urodynamics from 1993 to 2012.
AB  - AIMS: To assess the quality of randomized controlled trials (RCTs) published in
      Neurourology and Urodynamics (NAU) by using three types of analytical tools.
      METHODS: MEDLINE was used to extract RCTs from original articles published in the
      NAU from 1993 to 2012. The relationship between the number of articles and RCTs
      with time and that between various factors and the quality of RCTs were analyzed.
      To analyze the quality of the RCTs, the time period was divided into four
      sections and three tools were applied (e.g., the Jadad scale, van Tulder scale,
      and Cochrane Collaboration Risk of Bias Tool [CCRBT]). RESULTS: Among the 1,957
      original articles, 93 (4.75%) were RCTs. The ratio between the number of NAU and
      RCTs over time increased. The Jadad score for years 1993-1997 was 3.25 +/- 1.71,
      1998-2002 was 2.10 +/- 0.74, 2003-2007 was 2.09 +/- 1.12, and 2008-2012 was 2.80
      +/- 1.09 (P = 0.014). The van Tulder scales were 6.25 +/- 3.10, 4.40 +/- 1.65,
      4.97 +/- 1.99, and 5.93 +/- 1.98, respectively (P = 0.055). The CCRBT identified
      a low risk of bias in 1 (25%), 0 (0%), 1 (2.86%), and 5 (11.36%) articles,
      respectively. Trials with allocation concealment, Institutional review board
      (IRB) approval, and blinded studies had significantly higher quality than others.
      CONCLUSIONS: The quantitative increase of RCT presented in NAU over time was
      observed but there was no definite qualitative improvement. Effort is required to
      improve the quality of RCTs published in NAU from the design step.

PMID- 23868819
TI  - LDH-A acetylation: implication in cancer.

PMID- 23868820
TI  - The impact of hyperglycemia on risk of infection and early death during induction
      therapy for acute lymphoblastic leukemia (ALL).
AB  - Hyperglycemia during induction chemotherapy for childhood acute lymphoblastic
      leukemia (ALL) has been inconsistently associated with risk of infection. We
      investigated the incidence of hyperglycemia during induction for childhood ALL in
      a retrospective cohort study of 144 patients treated on a single national
      protocol (UKALL2003) and explored its association with infection. All patients
      received dexamethasone. Overt hyperglycemia was seen in 36% and proven bacterial
      or fungal infection was most common in this group (OR 4.1 (1.1-15.6), P = 0.039).
      Both hyperglycaemia and infection were particularly common in patients with Down
      Syndrome.

PMID- 23868821
TI  - Photoluminescence properties of aeschynite-type LaNbTiO6:RE3+ (RE = Tb, Dy, Ho)
      down-converting phosphors.
AB  - In this study, a series of LaNbTiO6:RE(3+) (RE = Tb, Dy, Ho) down-converting
      phosphors were synthesized using a modified sol-gel combustion method, and their
      photoluminescence (PL) properties were investigated as a function of activator
      concentration and annealing temperature. The resultant particles were
      characterized using X-ray diffraction, transmission electron microscopy, scanning
      electron microscopy, UV/Vis diffuse reflectance spectroscopy and PL spectra. The
      highly crystalline LaNbTiO6:RE(3+) (RE = Tb, Dy, Ho) phosphors with an average
      size of 200-300 nm obtained at 1100 degrees C have an orthorhombic aeschynite
      type structure and exhibit the highest luminescent intensity in our study range.
      The emission spectra of LaNbTiO6:RE(3+) (RE = Tb, Dy, Ho) phosphors under
      excitations at UV/blue sources are mainly composed of characteristic peaks
      arising from the f-f transitions of RE(3+), including 489 nm ((5) D4 -> (7) F6)
      and 545 nm ((5) D4 -> (7) F5) for Tb(3+), 476 and 482 nm ((4) F9/2 -> (6) H15/2)
      and 571 nm ((4) F9/2 -> (6) H13/2) for Dy(3+), and 545 nm ((5) F4 + (5) S2 -> (5)
      I8) for Ho(3+), respectively. The luminescent mechanisms were further
      investigated. It can be expected that these phosphors are of intense interest and
      potential importance for many optical applications.

PMID- 23868822
TI  - Occupational carbon monoxide fatalities in the US from unintentional non-fire
      related exposures, 1992-2008.
AB  - OBJECTIVE: To analyze characteristics of, and trends in, work-related carbon
      monoxide (CO) fatalities in the US. METHODS: Records of unintentional, non-fire
      related fatalities from CO exposure were extracted from the Bureau of Labor
      Statistics' Census of Fatal Occupational Injuries and the Occupational Safety and
      Health Administration's Integrated Management Information System for years 1992
      2008 and analyzed separately. RESULTS: The average number of annual CO fatalities
      was 22 (standard deviation=8). Fatality rates were highest among workers
      aged>=65, males, Hispanics, winter months, the Midwest, and the Fishing, Hunting,
      and Trapping industry subsector. Self-employed workers accounted for 28% of all
      fatalities. Motor vehicles were the most frequent source of fatal CO exposure,
      followed by heating systems and generators. CONCLUSIONS: CO has been the most
      frequent cause of occupational fatality due to acute inhalation, and has shown no
      significant decreasing trend since 1992. The high number of fatalities from motor
      vehicles warrants further investigation.

PMID- 23868823
TI  - Serum proteomics in amnestic mild cognitive impairment.
AB  - We have explored proteins related to mild cognitive impairment (MCI). The serum
      proteome of 35 amnestic MCI patients and 35 cognitively healthy persons was
      investigated by LC MS. We identified 108 differentially expressed peptides
      between MCI patients and controls, belonging to 39 proteins. Eight proteins were
      selected for further investigation by quantitative protein measurements using a
      MRM assay; apolipoprotein E, carboxypeptidase N subunit 2, complement factor B
      (CFAB), galectin-3 binding protein (LG3BP), lumican, serum amyloid A-4 protein
      (SAA4), serum amyloid P-component, and sex hormone binding globulin. Results of
      the quantitative protein measurements showed significantly decreased levels of
      carboxypeptidase N subunit 2, CFAB, LG3BP, SAA4, and serum amyloid P-component in
      serum from amnestic MCI patients compared with cognitive healthy controls (two
      sided t-test; p < 0.05). Apolipoprotein E and lumican showed no significant
      difference in protein levels, sex hormone binding globulin could not be
      quantified since the MRM assay did not reach the required sensitivity. A model
      based on the three most significantly decreased proteins (CFAB, LG3BP, and SAA4)
      showed a sensitivity and specificity of 73 and 66%, respectively, for the initial
      sample set. A small external validation set yielded 77% sensitivity and 75%
      specificity.

PMID- 23868824
TI  - Protein arginine allylation and subsequent fluorophore targeting.
AB  - Protein allylation and fluorophore targeting: Arginine residues of the yeast
      nuclear ribonucleoprotein Npl3 were extensively modified by Hmt1-catalyzed
      allylation reaction with allyl-SAM as the allyl group donor. The allylated
      protein was further treated with tetrazole compounds under UV irradiation,
      leading to formation of protein-attached fluorescent products. 

PMID- 23868825
TI  - Decoding noncoding RNA: da Vinci redux?

PMID- 23868826
TI  - Circulating p53-responsive microRNAs as predictive biomarkers in heart failure
      after acute myocardial infarction: the long and arduous road from scientific
      discovery to clinical utility.

PMID- 23868827
TI  - An unexpected switch: regulation of cardiomyocyte proliferation by the homeobox
      gene meis1.

PMID- 23868828
TI  - Two ways to make great contributions.

PMID- 23868829
TI  - Genetics of thoracic aortic aneurysm: at the crossroad of transforming growth
      factor-beta signaling and vascular smooth muscle cell contractility.
AB  - Aortic aneurysm, including both abdominal aortic aneurysm and thoracic aortic
      aneurysm, is the cause of death of 1% to 2% of the Western population. This
      review focuses only on thoracic aortic aneurysms and dissections. During the past
      decade, the genetic contribution to the pathogenesis of thoracic aortic aneurysms
      and dissections has revealed perturbed extracellular matrix signaling cascade
      interactions and deficient intracellular components of the smooth muscle
      contractile apparatus as the key mechanisms. Based on the study of different
      Marfan mouse models and the discovery of several novel thoracic aortic aneurysm
      genes, the involvement of the transforming growth factor-beta signaling pathway
      has opened unexpected new avenues. Overall, these discoveries have 3 important
      consequences. First, the pathogenesis of thoracic aortic aneurysms and
      dissections is better understood, although some controversy still exists. Second,
      the management strategies for the medical and surgical treatment of thoracic
      aortic aneurysms and dissections are becoming increasingly gene-tailored. Third,
      the pathogenetic insights have delivered new treatment options that are currently
      being investigated in large clinical trials. 

PMID- 23868830
TI  - Pericytes in development and pathology of skeletal muscle.
AB  - Increasing attention is currently devoted to the multiple roles that pericytes
      (also defined as mural, Rouget, or perivascular cells) may play during
      angiogenesis, vascular homeostasis, and pathology. Many recent excellent reviews
      thoroughly address these topics (see below); hence, we will not discuss them in
      detail here. However, not much is known about origin, heterogeneity, gene
      expression, and developmental potential of pericytes during fetal and postnatal
      development. This is likely because of the paucity of markers expressed by
      pericytes and the absence of truly unique ones. Thus, in vivo identification and
      ex perspective isolation are challenging and explain the relative little data
      available in comparison with neighbor but far more characterized cells such as
      the endothelium. Despite this preliminary knowledge, we will propose that
      contribution to growing mesoderm tissues may be an important role for pericytes.
      Thus, their ability to contribute to tissue regeneration may be a consequence of
      their role in tissue growth. However, in a severely damaged or diseased tissue,
      acute or chronic inflammation likely results in the production of signaling
      molecules that are different from those present in developing tissues, thus
      explaining why pericytes are easily diverted from a regenerative to a fibrotic
      fate. 

PMID- 23868831
TI  - Prenatal abnormal features of the fourth ventricle in Joubert syndrome and
      related disorders.
AB  - Joubert syndrome and related disorders (JSRD) are characterized by absence or
      underdevelopment of the cerebellar vermis and a malformed brainstem. This family
      of disorders is a member of an emerging class of diseases called ciliopathies. We
      describe the abnormal features of the brain, particularly the fourth ventricle,
      in seven fetuses affected by JSRD. In three cases abnormality of the fourth
      ventricle was isolated and in four cases there were associated malformations. The
      molar tooth sign (MTS) was always present and visible on two-dimensional
      ultrasound and, when performed, on three-dimensional ultrasound and magnetic
      resonance imaging. The fourth ventricle was always abnormal, in both axial and
      sagittal views, presenting pathognomonic deformities. It is important to identify
      JSRD, preferably prenatally or at least postnatally, due to its high risk of
      recurrence of about 25%. A detailed prenatal assessment of the fourth ventricle
      in several views may help to achieve this goal.

PMID- 23868832
TI  - TiO2 (B)/anatase composites synthesized by spray drying as high performance
      negative electrode material in li-ion batteries.

PMID- 23868833
TI  - The efficacy and safety of an office-based polypectomy with a vacuum-powered
      microdebrider.
AB  - BACKGROUND: The waiting time for functional endoscopic sinus surgery (FESS) in
      patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) in the
      Canadian public healthcare system can be lengthy. Many such patients have
      significant nasal obstruction resulting in a poor quality of life. A simple and
      safe office-based polypectomy device to debulk nasal polyps allows immediate
      alleviation of nasal obstruction and better access for topical medications. The
      aim of this study is to assess the efficacy, safety, and patient tolerability of
      a vacuum-powered microdebrider in the outpatient clinic setting. METHODS: The
      clinical charts of patients with CRSwNP who underwent office polypectomy with a
      vacuum-powered microdebrider between May 2012 and February 2013 were
      retrospectively reviewed. These patients were either awaiting surgery or had
      recurrent polyposis postsurgery that was amenable to office polypectomy.
      Previously completed procedural and clinical outcomes questionnaires by the
      patients and surgeon were analyzed. RESULTS: Sixty-eight patients underwent
      office polypectomy in this case series. Fifty-nine procedures (87%) were
      successfully completed. Failed complete polyp resections were due to fibrous
      polyps (n = 7; 10%), device failure (n = 1; 1.5%), and obstruction from a
      deviated nasal septum (n = 1; 1.5%). There was a 43% improvement in nasal
      obstruction score and significant reduction in polyp grade postpolypectomy.
      Majority of patients (n = 66; 97%) reported a comfort level of "fair" to
      "excellent." Bleeding was "light" in 61 cases (90%). There were no complications
      encountered. CONCLUSION: The vacuum-powered microdebrider is a safe, effective,
      and well-tolerated instrument to resect nonfibrous nasal polyps in the outpatient
      setting.

PMID- 23868834
TI  - An intersection of pediatrics and geriatrics.

PMID- 23868835
TI  - Honeybees can learn the relationship between the solar ephemeris and a newly
      experienced landscape: a confirmation.
AB  - Honeybees learn the spatial relationship between the sun's pattern of movement
      and the landscape immediately surrounding their nest, which allows bees to locate
      the sun under overcast skies by reference to the landscape alone. Surprisingly,
      when bees have been transplanted from their natal landscape to a rotated twin
      landscape - such as from one treeline to a similar but differently oriented
      treeline - they fail to learn the relationship between the sun and the second
      landscape. This raises the question of whether bees can ever learn the
      relationship between the sun's pattern of movement and a landscape other than
      their natal one. Here we confirm, with new and necessary controls, that bees can
      indeed learn the relationship between the sun's pattern of movement and a second
      (that is, non-natal) landscape, if the second landscape is panoramically
      different from the bees' natal site. We transplanted bees from their natal site
      to a panoramically different second site and, 3 days later, tested the bees'
      knowledge of the relationship between the sun and the second landscape. The test
      involved observing the bees' communicative dances under overcast skies at a third
      site that was a rotated twin of the second. These bees oriented their dances
      using a memory of the sun's course in relation to the second landscape,
      indicating that they had learned this relationship. Meanwhile, control bees
      transplanted directly from the natal site to the third site, skipping the second,
      danced differently, confirming the importance of the experimental bees'
      experience at the second site. 

PMID- 23868836
TI  - Lizard tricks: overcoming conflicting requirements of speed versus climbing
      ability by altering biomechanics of the lizard stride.
AB  - Adaptations promoting greater performance in one habitat are thought to reduce
      performance in others. However, there are many examples of animals in which,
      despite habitat differences, such predicted differences in performance do not
      occur. One such example is the relationship between locomotory performance to
      habitat for varanid lizards. To explain the lack of difference in locomotor
      performance we examined detailed observations of the kinematics of each lizard's
      stride. Differences in kinematics were greatest between climbing and non-climbing
      species. For terrestrial lizards, the kinematics indicated that increased femur
      adduction, femur rotation and ankle angle all contributed positively to changes
      in stride length, but they were constrained for climbing species, probably
      because of biomechanical restrictions on the centre of mass height (to increase
      stability on vertical surfaces). Despite climbing species having restricted
      stride length, no differences have been previously reported in sprint speed
      between climbing and non-climbing varanids. This is best explained by climbing
      varanids using an alternative speed modulation strategy of varying stride
      frequency to avoid the potential trade-off of speed versus stability on vertical
      surfaces. Thus, by measuring the relevant biomechanics for lizard strides, we
      have shown how kinematic differences among species can mask performance
      differences typically associated with habitat variation. 

PMID- 23868837
TI  - The protective effect of rapid cold-hardening develops more quickly in frozen
      versus supercooled larvae of the Antarctic midge, Belgica antarctica.
AB  - During the austral summer, larvae of the terrestrial midge Belgica antarctica
      (Diptera: Chironomidae) experience highly variable and often unpredictable
      thermal conditions. In addition to remaining freeze tolerant year-round, larvae
      are capable of swiftly increasing their cold tolerance through the rapid cold
      hardening (RCH) response. The present study compared the induction of RCH in
      frozen versus supercooled larvae. At the same induction temperature, RCH occurred
      more rapidly and conferred a greater level of cryoprotection in frozen versus
      supercooled larvae. Furthermore, RCH in frozen larvae could be induced at
      temperatures as low as -12 degrees C, which is the lowest temperature reported to
      induce RCH. Remarkably, as little as 15 min at -5 degrees C significantly
      enhanced larval cold tolerance. Not only is protection from RCH acquired swiftly,
      but it is also quickly lost after thawing for 2 h at 2 degrees C. Because the
      primary difference between frozen and supercooled larvae is cellular dehydration
      caused by freeze concentration of body fluids, we also compared the effects of
      acclimation in dehydrated versus frozen larvae. Because slow dehydration without
      chilling significantly increased larval survival to a subsequent cold exposure,
      we hypothesize that cellular dehydration caused by freeze concentration promotes
      the rapid acquisition of cold tolerance in frozen larvae. 

PMID- 23868838
TI  - Activity of intestinal carbohydrases responds to multiple dietary signals in
      nestling house sparrows.
AB  - The 'adaptive modulation hypothesis' predicts that activity of digestive enzymes
      should match the amount of their substrates in diet. Interestingly, many
      passerine birds do not adjust the activity of intestinal carbohydrases to dietary
      carbohydrate content. It is difficult to assess the generality of this rule,
      because in some studies passerines fed on low-carbohydrate and high-lipid diet
      showed reduced activity of intestinal carbohydrases. However, as carbohydrase
      activity may be inhibited by high dietary lipid content, it is unclear whether
      observed effects reflected lack of induction by the low carbohydrate levels or
      suppression by the high lipid levels. Here, we isolated the specific effects of
      dietary carbohydrate and lipid on carbohydrases. We hand-fed house sparrow
      nestlings on diets with 25% starch and 8% lipid (diet HS), no starch and 20%
      lipid (HL), or 25% starch and 20% lipid (HSL). Our results show that activity of
      intestinal carbohydrases is simultaneously induced by dietary carbohydrates and
      decreased by dietary lipid, although the latter effect seems stronger. Activities
      of maltase and sucrase summed over the total intestine decreased in the order
      HS>HSL>HL. We observed a complex interaction between diet composition and
      intestinal position for mass-specific activity of these enzymes, suggesting site
      specific responses to changes in digesta composition along the intestines caused
      by digestion and absorption. We re-interpret results of earlier studies and
      conclude that there is no unequivocal example of adaptive modulation of
      intestinal carbohydrases by dietary carbohydrate in adult passerine birds,
      whereas the present experiment confirms that nestlings of at least some species
      possess such capacity. 

PMID- 23868839
TI  - Seasonality influences cuticle melanization and immune defense in a cricket:
      support for a temperature-dependent immune investment hypothesis in insects.
AB  - To improve thermoregulation in colder environments, insects are expected to
      darken their cuticles with melanin via the phenoloxidase cascade, a phenomenon
      predicted by the thermal melanin hypothesis. However, the phenoloxidase cascade
      also plays a significant role in insect immunity, leading to the additional
      hypothesis that the thermal environment indirectly shapes immune function via
      direct selection on cuticle color. Support for the latter hypothesis comes from
      the cricket Allonemobius socius, where cuticle darkness and immune-related
      phenoloxidase activity increase with latitude. However, thermal environments vary
      seasonally as well as geographically, suggesting that seasonal plasticity in
      immunity may also exist. Although seasonal fluctuations in vertebrate immune
      function are common (because of flux in breeding or resource abundance),
      seasonality in invertebrate immunity has not been widely explored. We addressed
      this possibility by rearing crickets in simulated summer and fall environments
      and assayed their cuticle color and immune function. Prior to estimating
      immunity, crickets were placed in a common environment to minimize metabolic rate
      differences. Individuals reared under fall-like conditions exhibited darker
      cuticles, greater phenoloxidase activity and greater resistance to the bacteria
      Serratia marcescens. These data support the hypothesis that changes in the
      thermal environment modify cuticle color, which indirectly shapes immune
      investment through pleiotropy. This hypothesis may represent a widespread
      mechanism governing immunity in numerous systems, considering that most insects
      operate in seasonally and geographically variable thermal environments. 

PMID- 23868840
TI  - A conserved fertility signal despite population variation in the cuticular
      chemical profile of the trap-jaw ant Odontomachus brunneus.
AB  - Contact pheromones in the form of cuticular hydrocarbons are widespread among
      insects. Eusocial insects present a special challenge for understanding the
      evolution of the cuticular hydrocarbon profile because this blend is responsible
      for multiple distinct roles such as nestmate recognition and signalling fertility
      status. This study investigates these two signalling roles of the hydrocarbon
      profile in the trap-jaw ant Odontomachus brunneus. We demonstrate that the
      cuticular hydrocarbon profile is highly variable across populations and provide
      evidence that these differences are used for nestmate discrimination. Through
      manipulative experiments we also show that (Z)-9-nonacosene (Z9:C29) is used as a
      fertility signal and its role is conserved across populations. Our data
      demonstrate that both fertility and nestmate signalling influence the cuticular
      hydrocarbon profile and specifically the relative abundance of Z9:C29 on the
      cuticle of O. brunneus. Our study suggests that natural selection works on the
      cuticular chemical profile through multiple regulatory pathways, diversifying
      nestmate signals while conserving fertility signals. 

PMID- 23868841
TI  - Uptake, handling and excretion of Na+ and Cl- from the diet in vivo in freshwater
      and seawater-acclimated killifish, Fundulus heteroclitus, an agastric teleost.
AB  - A radiotracer approach using diets labelled with (22)Na(+), (36)Cl(-) and
      [(14)C]polyethylene-4000 (PEG-4000) was employed to investigate the role of
      intestinal uptake from the food in ion homeostasis in the killifish Fundulus
      heteroclitus. This euryhaline teleost lacks both a stomach and the capacity for
      Cl(-) uptake at the gills in freshwater. PEG-4000 appearance in the water was
      minimal up to 10-11 h post-feeding, indicating the virtual absence of Na(+) and
      Cl(-) loss in the faeces up until this time. Rapid uptake of dietary Na(+) and
      Cl(-) occurred and more than 88% of (22)Na(+) and (36)Cl(-) were absorbed in the
      intestine by 3 h post-feeding; excretion rates of Na(+) and Cl(-) originating
      from the food were greatest during this period. Uptake and excretion of Cl(-)
      from the diet was fivefold to sixfold greater than that of Na(+) in freshwater,
      and approximately threefold greater in seawater. Excretions of dietary Na(+) and
      Cl(-) by seawater-acclimated killifish were far greater than by freshwater
      acclimated killifish in this time frame, reflecting the much greater branchial
      efflux rates and turnover rates of the internal exchangeable pools. At both 3 and
      9 h post-feeding, the largest fraction of dietary Na(+) was found in the carcass
      of freshwater-acclimated fish, followed by the external water, and finally the
      digestive tract. However, in seawater-acclimated fish, more was excreted to the
      water, and less was retained in the carcass. For Cl(-), which was taken up and
      excreted more rapidly than Na(+), the majority of the dietary load had moved to
      the external water by 9 h in both freshwater and seawater animals. After 7 days
      training on a low-salt natural diet (live Lumbriculus variegatus worms; 31.5
      MUmol Na(+) g(-1) wet mass) versus a high-salt synthetic pellet diet (911 MUmol
      Na(+) g(-1) dry food mass), freshwater killifish exhibited a lower absolute
      excretion rate of Na(+) from the low-salt diet, but relative uptake from the
      intestine and retention in the carcass were virtually identical from the two
      diets. Seawater killifish excreted relatively more Na(+) from the low-salt diet.
      Overall, our results emphasize the importance of dietary Na(+) and Cl(-) in the
      electrolyte economy of the killifish, particularly in freshwater, and especially
      for Cl(-). 

PMID- 23868842
TI  - The role of hind limb tendons in gibbon locomotion: springs or strings?
AB  - Tendon properties have an important effect on the mechanical behaviour of
      muscles, with compliant tendons allowing near-isometric muscle contraction and
      facilitating elastic energy storage and recoil. Stiff tendons, in contrast,
      facilitate rapid force transfer and precise positional control. In humans, the
      long Achilles tendon contributes to the mechanical efficiency of running via
      elastic energy storage and recovery, and its presence has been linked to the
      evolution of habitual bipedalism. Gibbons also possess relatively long hind limb
      tendons; however, their role is as yet unknown. Based on their large dimensions,
      and inferring from the situation in humans, we hypothesize that the tendons in
      the gibbon hind limb will facilitate elastic energy storage and recoil during
      hind-limb-powered locomotion. To investigate this, we determined the material
      properties of the gibbon Achilles and patellar tendon in vitro and linked this
      with available kinematic and kinetic data to evaluate their role in leaping and
      bipedalism. Tensile tests were conducted on tendon samples using a material
      testing machine and the load-displacement data were used to calculate stiffness,
      Young's modulus and hysteresis. In addition, the average stress-in-life and
      energy absorption capacity of both tendons were estimated. We found a functional
      difference between the gibbon Achilles and patellar tendon, with the Achilles
      tendon being more suitable for elastic energy storage and release. The patellar
      tendon, in contrast, has a relatively high hysteresis, making it less suitable to
      act as elastic spring. This suggests that the gibbon Achilles tendon might fulfil
      a similar function as in humans, contributing to reducing the locomotor cost of
      bipedalism by acting as elastic spring, while the high stiffness of the patellar
      tendon might favour fast force transfer upon recoil and, possibly, enhance
      leaping performance. 

PMID- 23868843
TI  - A new approach to evaluate multimodal orientation behaviour of migratory
      passerine birds recorded in circular orientation cages.
AB  - Circular orientation cages have been used for several decades to record the
      migratory orientation of passerine migrants, and have been central to the
      investigation of the functional characteristics of the biological compasses used
      for orientation. The use of these cages offers unique possibilities to study the
      migratory behaviour of songbirds, but suffers from statistical limitations in
      evaluating the directions of the activity recorded in the cages. The migratory
      activity has been reported to vary, including complex multimodal orientation of
      migratory passerines tested in orientation cages irrespective of species studied.
      The currently applied circular statistical methods fail to describe orientation
      responses differing from unimodal and axial distributions. We propose for the
      first time a modelling procedure enabling the analysis of multimodal
      distributions at either an individual or a group level. In this paper we compare
      the results of conventional methods and the recommended modelling approach.
      Migratory routes may be more complex than a simple migratory direction, and
      multimodal behaviour in migratory species at the individual and population levels
      can be advantageous. Individuals may select the expected migratory direction, but
      may also return to safer sites en route, i.e. sites already known, which provide
      food and/or shelter in reverse directions. In individual birds, several
      directions may be expressed in the same test hour. At the species level,
      multimodal orientation may give an opportunity to expand the range or may refer
      to differential migration route preferences in different populations of birds. A
      conflicting experimental situation may also result in a different preferential
      orientation. In this paper we suggest a statistical solution to deal with these
      types of variations in orientation preference. 

PMID- 23868844
TI  - Sensitivity of ventilation and brain metabolism to ammonia exposure in rainbow
      trout, Oncorhynchus mykiss.
AB  - Ammonia has been documented as a respiratory gas that stimulates ventilation, and
      is sensed by peripheral neuroepithelial cells (NECs) in the gills in ammoniotelic
      rainbow trout. However, the hyperventilatory response is abolished in trout
      chronically exposed (1+ months) to high environmental ammonia [HEA; 250 MUmol l(
      1) (NH4)2SO4]. This study investigates whether the brain is involved in the acute
      sensitivity of ventilation to ammonia, and whether changes in brain metabolism
      are related to the loss of hyperventilatory responses in trout chronically
      exposed to HEA ('HEA trout'). Hyperventilation (via increased ventilatory
      amplitude rather than rate) and increased total ammonia concentration ([TAmm]) in
      brain tissue were induced in parallel by acute HEA exposure in control trout in a
      concentration-series experiment [500, 750 and 1000 MUmol l(-1) (NH4)2SO4], but
      these inductions were abolished in HEA trout. Ventilation was correlated more
      closely to [TAmm] in brain rather than to [TAmm] in plasma or cerebrospinal
      fluid. The close correlation of hyperventilation and increased brain [TAmm] also
      occurred in control trout acutely exposed to HEA in a time-series analysis [500
      MUmol l(-1) (NH4)2SO4; 15, 30, 45 and 60 min], as well as in a methionine
      sulfoxamine (MSOX) pre-injection experiment [to inhibit glutamine synthetase
      (GSase)]. These correlations consistently suggest that brain [TAmm] is involved
      in the hyperventilatory responses to ammonia in trout. The MSOX treatments,
      together with measurements of GSase activity, TAmm, glutamine and glutamate
      concentrations in brain tissue, were conducted in both the control and HEA trout.
      These experiments revealed that GSase plays an important role in transferring
      ammonia to glutamate to make glutamine in trout brain, thereby attenuating the
      elevation of brain [TAmm] following HEA exposure, and that glutamate
      concentration is reduced in HEA trout. The mRNAs for the ammonia channel proteins
      Rhbg, Rhcg1 and Rhcg2 were expressed in trout brain, and the expression of Rhbg
      and Rhcg2 increased in HEA trout, potentially as a mechanism to facilitate the
      efflux of ammonia. In summary, the brain appears to be involved in the
      sensitivity of ventilation to ammonia, and brain ammonia levels are regulated
      metabolically in trout. 

PMID- 23868845
TI  - Impact of temperature on performance in two species of South African dwarf
      chameleon, Bradypodion pumilum and B. occidentale.
AB  - Temperature is an extrinsic factor that influences reptile behavior because of
      its impact on reptile physiology. Understanding the impact of temperature on
      performance traits is important as it may affect the ecology and fitness of
      ectothermic animals such as reptiles. Here, we examined the temperature
      dependence of performance in two species of South African dwarf chameleon
      (Bradypodion): one adapted to a semi-arid environment and one to a mesic
      environment. Ecologically relevant performance traits were tested at different
      temperatures to evaluate their thermal dependence, and temperature-performance
      breadths for 80% and 90% of each performance trait were calculated. Our results
      show distinct differences in the thermal dependence of speed- versus force
      related performance traits. Moreover, our results show that the semi-arid species
      is better adapted to higher temperatures and as such has a better chance of
      coping with the predicted increases in environmental temperature. The mesic area
      adapted species seems to be more sensitive to an increase in temperature and
      could therefore potentially be threatened by the predicted future climate change.
      However, further studies investigating the potential for acclimation in
      chameleons are needed to better understand how animals may respond to future
      climate change. 

PMID- 23868846
TI  - Adjustments of global and local hindlimb properties during terrestrial locomotion
      of the common quail (Coturnix coturnix).
AB  - Previous research has resulted in increasing insight into neuro-mechanical
      control strategies during perturbed locomotion. In contrast, more general
      analyses on simple model (template)-related parameters during avian terrestrial
      locomotion are still rare. Quail kinematic data obtained using X-ray videography
      combined with ground reaction force measurements were used as a basis to
      investigate how 'global' template and 'local' leg joint parameters in this small,
      predominantly terrestrial bird change with speed and gait. Globally, quail
      locomotion approximates a spring-like behavior in all investigated gaits.
      However, ground reaction forces are more vertically oriented, which may help to
      balance the trunk. At the joint level, practically all the spring-like work was
      found to occur in the intertarsal joint (ITJ). From walking to grounded running,
      the local stiffness of the ITJ decreases similarly to the reduction observed in
      global leg stiffness. Thus, in gaits without aerial phases the quails may
      modulate ITJ stiffness to regulate global leg stiffness, and therefore gait
      changes, to a significant degree. At higher speeds both global leg compression
      and stiffness are increased (the latter to values not significantly different to
      those obtained during walking). This enables the animals to shorten contact time
      and to generate aerial phases (running). However, we did not observe a change in
      the stiffness in the ITJ with a change of gait from grounded running to running.
      We hypothesize that a more extended leg at touch-down, controlled by the joint
      angles in the knee and ITJ, has an important influence in the leg stiffness
      adjustment process during running. 

PMID- 23868847
TI  - Differential expression and novel permeability properties of three aquaporin 8
      paralogs from seawater-challenged Atlantic salmon smolts.
AB  - Aquaporins may facilitate transepithelial water absorption in the intestine of
      seawater (SW)-acclimated fish. Here we have characterized three full-length aqp8
      paralogs from Atlantic salmon (Salmo salar). Bayesian inference revealed that
      each paralog is a representative of the three major classes of aqp8aa, aqp8ab and
      aqp8b genes found in other teleosts. The permeability properties were studied by
      heterologous expression in Xenopus laevis oocytes, and the expression levels
      examined by qPCR, immunofluorescence and immunoelectron microscopy, and
      immunoblotting of membrane fractions from intestines of SW-challenged smolts. All
      three Aqp8 paralogs were permeable to water and urea, whereas Aqp8ab and -8b
      were, surprisingly, also permeable to glycerol. The mRNA tissue distribution of
      each paralog was distinct, although some tissues such as the intestine showed
      redundant expression of more than one paralog. Immunofluorescence microscopy
      localized Aqp8aa(1+2) to intracellular compartments of the liver and intestine,
      and Aqp8ab and Aqp8b to apical plasma membrane domains of the intestinal
      epithelium, with Aqp8b also in goblet cells. In a control experiment with rainbow
      trout, immunoelectron microscopy confirmed abundant labeling of Aqp8ab and -8b at
      apical plasma membranes of enterocytes in the middle intestine and also in
      subapical vesicular structures. During SW challenge, Aqp8ab showed significantly
      increased levels of protein expression in plasma-membrane-enriched fractions of
      the intestine. These data indicate that the Atlantic salmon Aqp8 paralogs have
      neofunctionalized on a transcriptional as well as a functional level, and that
      Aqp8ab may play a central role in the intestinal transcellular uptake of water
      during SW acclimation. 

PMID- 23868848
TI  - Mechanical tuning of the moth ear: distortion-product otoacoustic emissions and
      tympanal vibrations.
AB  - The mechanical tuning of the ear in the moth Empyreuma pugione was investigated
      by distortion-product otoacoustic emissions (DPOAE) and laser Doppler vibrometry
      (LDV). DPOAE audiograms were assessed using a novel protocol that may be
      advantageous for non-invasive auditory studies in insects. To evoke DPOAE, two
      tone stimuli within frequency and level ranges that generated a large matrix of
      values (960 frequency-level combinations) were used to examine the acoustic space
      in which the moth tympanum shows its best mechanical and acoustical responses.
      The DPOAE tuning curve derived from the response matrix resembles that obtained
      previously by electrophysiology, and is V-shaped and tuned to frequencies between
      25 and 45 kHz with low Q10dB values of 1.21+/-0.26. In addition, while using a
      comparable stimulation regime, mechanical distortion in the displacement of the
      moth's tympanal membrane at the stigma was recorded with a laser Doppler
      vibrometer. The corresponding mechanical vibration audiograms were compared with
      DPOAE audiograms. Both types of audiograms have comparable shape, but most of the
      mechanical response fields are shifted towards lower frequencies. We showed for
      the first time in moths that DPOAE have a pronounced analogy in the vibration of
      the tympanic membrane where they may originate. Our work supports previous
      studies that point to the stigma (and the internally associated transduction
      machinery) as an important place of sound amplification in the moth ear, but also
      suggests a complex mechanical role for the rest of the transparent zone. 

PMID- 23868849
TI  - A yellow fluorescent protein with reduced chloride sensitivity engineered by loop
      insertion.
AB  - Light it up! We demonstrate a novel way to reduce the chloride sensitivity of
      yellow fluorescent protein by inserting glycine residues in its loop region. The
      length and position for the insertion were optimized experimentally, and a
      plausible underlying mechanism is proposed. 

PMID- 23868850
TI  - Populus cathayana males are less affected than females by excess manganese:
      comparative proteomic and physiological analyses.
AB  - The comprehension of sexually different responses in dioecious plants to excess
      manganese (Mn) stress requires molecular explanation. Physiological and proteomic
      changes in leaves of Populus cathayana males and females were analyzed after 4 wk
      of exposure to Mn stress. Under excess Mn conditions, shoot height and
      photosynthesis decreased more in females than in males. Females also showed
      severe browning and subcellular damage, higher Mn2+ absorption, and different
      antioxidant enzyme activities compared with males. There were ten differently
      regulated protein spots induced by excess Mn stress. They were mainly related to
      photosynthesis, ROS cleaning, and cell signaling associated to ROS, plant cell
      death, heat shock, cell defense and rescue, and gene expression and regulation.
      Variation in protein expression between the sexes clearly showed that males have
      evolved more efficient photosynthesis capacity, more stable gene expression and
      regulation, and better cell defense and rescue to prevent further injury under
      excess Mn stress.

PMID- 23868851
TI  - QnAs with Ronald DePinho. Interview by Prashant Nair.

PMID- 23868853
TI  - Proton transfer through the water gossamer.
AB  - The diffusion of protons through water is understood within the framework of the
      Grotthuss mechanism, which requires that they undergo structural diffusion in a
      stepwise manner throughout the water network. Despite long study, this picture
      oversimplifies and neglects the complexity of the supramolecular structure of
      water. We use first-principles simulations and demonstrate that the currently
      accepted picture of proton diffusion is in need of revision. We show that proton
      and hydroxide diffusion occurs through periods of intense activity involving
      concerted proton hopping followed by periods of rest. The picture that emerges is
      that proton transfer is a multiscale and multidynamical process involving a
      broader distribution of pathways and timescales than currently assumed. To
      rationalize these phenomena, we look at the 3D water network as a distribution of
      closed directed rings, which reveals the presence of medium-range directional
      correlations in the liquid. One of the natural consequences of this feature is
      that both the hydronium and hydroxide ion are decorated with proton wires. These
      wires serve as conduits for long proton jumps over several hydrogen bonds. 

PMID- 23868852
TI  - NMR paves the way for atomic level descriptions of sparsely populated,
      transiently formed biomolecular conformers.
AB  - The importance of dynamics to biomolecular function is becoming increasingly
      clear. A description of the structure-function relationship must, therefore,
      include the role of motion, requiring a shift in paradigm from focus on a single
      static 3D picture to one where a given biomolecule is considered in terms of an
      ensemble of interconverting conformers, each with potentially diverse activities.
      In this Perspective, we describe how recent developments in solution NMR
      spectroscopy facilitate atomic resolution studies of sparsely populated,
      transiently formed biomolecular conformations that exchange with the native
      state. Examples of how this methodology is applied to protein folding and
      misfolding, ligand binding, and molecular recognition are provided as a means of
      illustrating both the power of the new techniques and the significant roles that
      conformationally excited protein states play in biology. 

PMID- 23868855
TI  - A novel device for delivery of intranasal particulate medication: a pilot study.
AB  - BACKGROUND: Intranasal medication delivery for allergic rhinitis (AR) is
      considered a mainstay of therapy but is hampered by poor compliance. Among
      reasons given are unpleasant sensations associated with spray penetration into
      the pharynx. Our objective was to study a novel method of particle delivery to
      the nose that would abrogate these issues. METHODS: This was a double-blind,
      randomized study. Subjects who met study criteria underwent intranasal particle
      delivery using a novel device (Trivair Nasal Deposition System; Trimel
      Pharmaceuticals, Toronto, Canada) that delivered anhydrous lactose particles into
      the nose via a transoral air puff (thus elevating soft palate and blocking the
      nasopharynx). Subjects had nostrils randomized into 4 groups (particle sizes 5
      MUm and 50 MUm * doses 12.5 mg and 25 mg). Particle deposition was assessed at 1
      minute, 10 minutes, and 30 minutes on the inferior turbinate, middle turbinate,
      and nasopharynx, respectively, using high-definition endoscopic photography. Each
      image was compared using an expert blinded 2-person panel for percentage
      particles remaining. Nonparametric data was assessed using the Wilcoxon signed
      rank test via Strata software. RESULTS: Twelve nostrils in total met study
      criteria. The results showed no difference in effectiveness of nasal particle
      retention between the groups based on particle size or dose. No particles entered
      the nasopharynx or oropharynx. CONCLUSION: This study provides proof-of-principle
      data that the Trivair Nasal Deposition System is effective at retaining
      medication in the nose without pharyngeal penetration. Larger studies on this
      device are warranted.

PMID- 23868854
TI  - Inhibition of in vitro and in vivo brown fat differentiation program by
      myostatin.
AB  - OBJECTIVE: Obesity arises mainly due to the imbalance between energy storage and
      its expenditure. Metabolically active brown adipose tissue (BAT) has recently
      been detected in humans and has been proposed as a new target for anti-obesity
      therapy because of its unique capacity to regulate energy expenditure. Myostatin
      (Mst), a negative regulator of muscle mass, has been identified as a potential
      target to regulate overall body composition. Although the beneficial effects of
      Mst inhibition on muscle mass are well known, its role in the regulation of lipid
      metabolism, and energy expenditure is not very clear. DESIGN AND METHODS: We
      tested the effects of Mst inhibition on the gene regulatory networks that control
      BAT differentiation using both in vivo and in vitro model systems. PRDM16 and
      UCP1, two key regulators of brown fat differentiation were significantly up
      regulated in levator-ani (LA) and gastrocnemius (Gastroc) muscles as well as in
      epididymal (Epi) and subcutaneous (SC) fat pads isolated from Mst knock out (Mst
      KO) male mice compared with wild type (WT) mice. RESULTS: Using mouse embryonic
      fibroblast (MEFs) primary cultures obtained from Mst KO group compared to the WT
      group undergoing adipogenic differentiation, we also demonstrate a significant
      increase in select genes and proteins that improve lipid metabolism and energy
      expenditure. CONCLUSION: Treatment of Mst KO MEFs with recombinant Mst protein
      significantly inhibited the gene expression levels of UCP1, PRDM16, PGC1
      alpha/beta as well as BMP7. Future studies to extend these findings and explore
      the therapeutic potential of Mst inhibition on metabolic disorders are warranted.

PMID- 23868856
TI  - Mouse model resembling human lung cancer.

PMID- 23868857
TI  - Triplet-triplet annihilation upconversion based nanocapsules for bioimaging under
      excitation by red and deep-red light.
AB  - Non-toxic and biocompatible triplet-triplet annihilation upconversion based
      nanocapsules (size less than 225 nm) were successfully fabricated by the
      combination of miniemulsion and solvent evaporation techniques. A first type of
      nanocapsules displays an upconversion spectrum characterized by the maximum of
      emission at lambdamax = 550 nm under illumination by red light, lambdaexc = 633
      nm. The second type of nanocapsules fluoresces at lambdamax = 555 nm when excited
      with deep-red light, lambdaexc = 708 nm. Conventional confocal laser scanning
      microscopy (CLSM) and flow cytometry were applied to determine uptake and
      toxicity of the nanocapsules for various (mesenchymal stem and HeLa) cells. Red
      light (lambdaexc = 633 nm) with extremely low optical power (less than 0.3 MUW)
      or deep-red light (lambdaexc = 708 nm) was used in CLSM experiments to generate
      green upconversion fluorescence. The cell images obtained with upconversion
      excitation demonstrate order of magnitude better signal to background ratio than
      the cell images obtained with direct excitation of the same fluorescence marker.

PMID- 23868859
TI  - SAFE combinations fail to open the door to atrial fibrillation prevention.

PMID- 23868858
TI  - Prospective randomized study to assess the efficacy of site and rate of atrial
      pacing on long-term progression of atrial fibrillation in sick sinus syndrome:
      Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study.
AB  - BACKGROUND: Atrial-based pacing is associated with lower risk of atrial
      fibrillation (AF) in sick sinus syndrome compared with ventricular pacing;
      nevertheless, the impact of site and rate of atrial pacing on progression of AF
      remains unclear. We evaluated whether long-term atrial pacing at the right atrial
      (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous
      atrial overdrive pacing algorithm can prevent the development of persistent AF.
      METHODS AND RESULTS: We randomized 385 patients with paroxysmal AF and sick sinus
      syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98),
      RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The
      primary outcome was the occurrence of persistent AF (AF documented at least 7
      days apart or need for cardioversion). Demographic data were homogeneous across
      both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF).
      After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients
      (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA
      septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence
      interval, 0.79-1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF
      (hazard ratio=1.17; 95% confidence interval, 0.79-1.74; P=0.69) did not prevent
      the development of persistent AF. CONCLUSIONS: In patients with paroxysmal AF and
      sick sinus syndrome requiring pacemaker implantation, an alternative atrial
      pacing site at the RA septum or continuous atrial overdrive pacing did not
      prevent the development of persistent AF. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00419640.

PMID- 23868860
TI  - Study of the selective uptake progress of aptamer-modified PLGA particles by
      liver cells.
AB  - It is of paramount importance to study the cellular uptake processes of particles
      with defined surface property, especially the uptake pathways and intracellular
      transportation. In this study, aptamer AS1411 molecules, which are known to
      specifically bind the over-expressed nucleolin on cancer cell membrane, were
      conjugated onto bovine serum albumin-decorated poly(D,L-lactide-co-glycolide;
      PLGA, Phi400 nm) particles with a density of 1-1.7 molecule/10 nm(2). The aptamer
      modified PLGA particles were preferably ingested by liver cancer cells with
      higher amount and faster rate. The clathrin-mediated endocytosis and
      macropinocytosis pathways played a more important role in uptake of the aptamer
      modified particles.

PMID- 23868863
TI  - The influence of platelet-rich plasma on myogenic differentiation.
AB  - The ability to expand and direct both precursor and stem cells towards a
      differential fate is considered extremely advantageous in tissue engineering.
      Platelet-rich plasma (PRP) possesses a milieu of growth factors and cytokines,
      which have the potential to have either a differentiative or proliferative
      influence on the cell type tested. Here, we investigated the effect of PRP on
      C2C12 myoblasts. A range of PRP concentrations in differentiation media was used
      to determine whether a concentration dependence existed, while PRP embedded in
      fibres of aligned electrospun polydioxanone and polycaprolactone was used to
      determine whether this presence of fibres would cause any differences in
      response. In both cases, it was found that late myogenic markers were suppressed
      after 7 days in culture. However, an early differentiation marker, MyoD, was
      upregulated during this same time period. The results from this study represent
      the ability of PRP to have an influence over both myogenic proliferation and
      differentiation, a factor which could prove useful in future studies involved
      with skeletal muscle tissue engineering.

PMID- 23868864
TI  - Surfactant-free, lipo-polymersomes stabilized by iron oxide nanoparticles/polymer
      interlayer for synergistically targeted and magnetically guided gene delivery.
AB  - Gene therapy holds promise to suppress carcinomas but still remains far removed
      from clinic because of the lack of a safe and effective delivery system. Besides
      enhancing transfection efficiency, the difficulty in gene therapy is how to
      deliver sufficient gene molecules to the site of interest. Herein, the rational
      design of surfactant-free lipo-polymersomes (LPPs) to overcome these problems is
      reported, simultaneously using a lipid-stabilized double emulsion approach. The
      LPPs are designed to conceal the cationic lipids and plasmid DNA inside the core
      along with iron oxide nanoparticles/polymer interlayer and a relatively neutral
      lipid shell to avoid the undesired interaction during circulation, leading to
      high accumulation in the tumors of mice. Furthermore, guided by an external
      magnetic field and the folic acid (FA) that target tumors via folate receptor
      mediated endocytosis on the cell surface, the vectors demonstrate a 30-40-fold
      increase in cell uptake. Moreover, this synergistic tumor-targeted approach can
      enhance a 10-fold increase in in vivo transfection efficacy by promoting the
      delivery of LPPs to cancer cells and facilitating the endosomal escape of gene
      molecules. The new insights and capabilities represent a major step in nanovector
      engineering for safe and efficient gene delivery. 

PMID- 23868865
TI  - Characterization of chondrocyte sheets prepared using a co-culture method with
      temperature-responsive culture inserts.
AB  - Conventional culture methods using temperature-responsive culture dishes require
      4-5 weeks to prepare layered chondrocyte sheets that can be used in articular
      cartilage repair and regeneration. This study investigated whether the use of
      synovial tissue obtained from the same joint as the chondrocyte nutritive supply
      source could more quickly facilitate the preparation of chondrocyte sheets. After
      culturing derived synoviocytes and chondrocytes together (i.e. combined culture
      or co-culture) on temperature-responsive inserts, chondrocyte growth was assessed
      and a molecular analysis of the chondrocyte sheets was performed. Transplantable
      tissue could be obtained more quickly using this method (average 10.5 days). Real
      time polymerase chain reaction and immunostaining of the three-layer chondrocyte
      sheets confirmed the significant expression of genes critical to cartilage
      maintenance, including type II collagen (COL2), aggrecan-1 and tissue
      metallopeptidase inhibitor 1. However, the expression of COL1, matrix
      metalloproteinase 3 (MMP3), MMP13 and A-disintegrin and metalloproteinase with
      thrombospondin motifs 5 was suppressed. The adhesive factor fibronectin-1 (FN1)
      was observed in all sheet layers, whereas in sheets generated using conventional
      preparation methods positive FN1 immunostaining was observed only on the surface
      of the sheets. The results indicate that synoviocyte co-cultures provide an
      optimal environment for the preparation of chondrocyte sheets for tissue
      transplantation and are particularly beneficial for shortening the required
      culture period. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 23868866
TI  - A structured judgement method to enhance mortality case note review: development
      and evaluation.
AB  - BACKGROUND: Case note review remains a prime means of retrospectively assessing
      quality of care. This study examines a new implicit judgement method, combining
      structured reviewer comments with quality of care scores, to assess care of
      people who die in hospital. METHODS: Using 1566 case notes from 20 English
      hospitals, 40 physicians each reviewed 30-40 case notes, writing structured
      judgement-based comments on care provided within three phases of care, and on
      care overall, and scoring quality of care from 1 (unsatisfactory) to 6 (very best
      care). Quality of care comments on 119 people who died (7.6% of the cohort) were
      analysed independently by two researchers to investigate how well reviewers
      provided structured short judgement notes on quality of care, together with
      appropriate care scores. Consistency between explanatory textual data and related
      scores was explored, using overall care score to group cases. RESULTS: Physician
      reviewers made informative, clinical judgement-based comments across all phases
      of care and usually provided a coherent quality of care score relating to each
      phase. The majority of comments (83%) were explicit judgements. About a fifth of
      patients were considered to have received less than satisfactory care, often
      experiencing a series of adverse events. CONCLUSIONS: A combination of implicit
      judgement, explicit explanatory comment and related quality of care scores can be
      used effectively to review the spectrum of care provided for people who die in
      hospital. The method can be used to quickly evaluate deaths so that lessons can
      be learned about both poor and high quality care.

PMID- 23868867
TI  - Value of a modified early obstetric warning system (MEOWS) in managing maternal
      complications in the peripartum period: an ethnographic study.
AB  - OBJECTIVE: To explore implementation of the modified early obstetric warning
      system (MEOWS) in practice to further understanding about the influence of
      contextual factors. METHODS: An ethnographic study using observations (>120 h),
      semi-structured interviews (n=45) and documentary review was performed in the
      maternity services in two UK hospitals over a 7-month period. Doctors, midwives
      and managers participated in the study and data were analysed thematically.
      RESULTS: For women admitted to hospital in the antenatal and postnatal period
      with an established risk of morbidity, the MEOWS enabled communication about
      vital signs from junior to senior midwives and obstetricians. The trigger prompts
      helped shape shared understandings of maternal complications. However, midwifery
      and obstetric staff questioned the added value of an extra chart in the postnatal
      period given the low incidence of maternal complications and the resulting
      increase in workload. In an effort to prioritise workload demands and respond to
      the immediate needs of both women and their babies, midwives exercised
      professional discretion regarding its use. However, discretionary use of MEOWS
      meant the loss of a potential universal safety net for detection of
      deterioration. CONCLUSIONS: Despite a decade of use in acute settings, research
      into the effectiveness of early warning systems still yields conflicting results.
      Widespread policy support for the MEOWS is based on its intuitive appeal and no
      validated system for use in the maternity population currently exists. Our
      findings suggest that, while the MEOWS has value in structuring the surveillance
      of hospitalised women with an established risk of morbidity, the complexities of
      managing risk and safety within the maternity pathway, the associated opportunity
      costs of MEOWS and variation in implementation currently call into question its
      role for routine use.

PMID- 23868868
TI  - Experience of general hospital care in older patients with cognitive impairment:
      are we measuring the most vulnerable patients' experience?

PMID- 23868869
TI  - Molecular pathways: coexpression of immune checkpoint molecules: signaling
      pathways and implications for cancer immunotherapy.
AB  - The expression of immune checkpoint molecules on T cells represents an important
      mechanism that the immune system uses to regulate responses to self-proteins.
      Checkpoint molecules include cytotoxic T lymphocyte antigen-4, programmed death
      1, lymphocyte activation gene-3, T-cell immunoglobulin and mucin protein-3, and
      several others. Previous studies have identified individual roles for each of
      these molecules, but more recent data show that coexpression of checkpoint
      molecules occurs frequently on cancer-specific T cells as well as on pathogen
      specific T cells in chronic infections. As the signaling pathways associated with
      each checkpoint molecule have not been fully elucidated, blocking multiple
      checkpoints with specific monoclonal antibodies results in improved outcomes in
      several chronic viral infections as well as in a wide array of preclinical models
      of cancer. Recent clinical data suggest similar effects in patients with
      metastatic melanoma. These findings support the concept that individual immune
      checkpoint molecules may function through nonoverlapping molecular mechanisms.
      Here, we review current data regarding immune checkpoint molecule signaling and
      coexpression, both in cancer and infectious disease, as well as the results of
      preclinical and clinical manipulations of checkpoint proteins.

PMID- 23868870
TI  - Molecular pathways: inflammation-associated nitric-oxide production as a cancer
      supporting redox mechanism and a potential therapeutic target.
AB  - It is widely accepted that many cancers express features of inflammation, driven
      by both microenvironmental cells and factors, and the intrinsic production of
      inflammation-associated mediators from malignant cells themselves. Inflammation
      results in intracellular oxidative stress with the ultimate biochemical oxidants
      composed of reactive nitrogens and oxygens. Although the role of inflammation in
      carcinogensis is well accepted, we now present data showing that inflammatory
      processes are also active in the maintenance phase of many aggressive forms of
      cancer. The oxidative stress of inflammation is proposed to drive a continuous
      process of DNA adducts and crosslinks, as well as posttranslational modifications
      to lipids and proteins that we argue support growth and survival. In this
      perspective, we introduce data on the emerging science of inflammation-driven
      posttranslational modifications on proteins responsible for driving growth,
      angiogenesis, immunosuppression, and inhibition of apoptosis. Examples include
      data from human melanoma, breast, head and neck, lung, and colon cancers.
      Fortunately, numerous antioxidant agents are clinically available, and we further
      propose that the pharmacologic attenuation of these inflammatory processes,
      particularly the reactive nitrogen species, will restore the cancer cells to an
      apoptosis-permissive and growth-inhibitory state. Our mouse model data using an
      arginine antagonist that prevents enzymatic production of nitric oxide directly
      supports this view. We contend that selected antioxidants be considered as part
      of the cancer treatment approach, as they are likely to provide a novel and
      mechanistically justified addition for therapeutic benefit.

PMID- 23868871
TI  - Stretchable, multiplexed pH sensors with demonstrations on rabbit and human
      hearts undergoing ischemia.
AB  - Stable pH is an established biomarker of health, relevant to all tissues of the
      body, including the heart. Clinical monitoring of pH in a practical manner, with
      high spatiotemporal resolution, is particularly difficult in organs such as the
      heart due to its soft mechanics, curvilinear geometry, heterogeneous surfaces,
      and continuous, complex rhythmic motion. The results presented here illustrate
      that advanced strategies in materials assembly and electrochemical growth can
      yield interconnected arrays of miniaturized IrOx pH sensors encapsulated in thin,
      low-modulus elastomers to yield conformal monitoring systems capable of
      noninvasive measurements on the surface of the beating heart. A thirty channel
      custom data acquisition system enables spatiotemporal pH mapping with a single
      potentiostat. In vitro testing reveals super-Nernstian sensitivity with excellent
      uniformity (69.9 +/- 2.2 mV/pH), linear response to temperature (-1.6 mV  degrees
      C(-1) ), and minimal influence of extracellular ions (<3.5 mV). Device examples
      include sensor arrays on balloon catheters and on skin-like stretchable
      membranes. Real-time measurement of pH on the surfaces of explanted rabbit hearts
      and a donated human heart during protocols of ischemia-reperfusion illustrate
      some of the capabilities. Envisioned applications range from devices for
      biological research, to surgical tools and long-term implants.

PMID- 23868872
TI  - Single circulating tumor cell sequencing for monitoring.

PMID- 23868873
TI  - Transforming growth factor-beta1 inhibits tissue engineering cartilage absorption
      via inducing the generation of regulatory T cells.
AB  - The objective of the present study was to explore the mechanisms of transforming
      growth factor (TGF)-beta1 inhibiting the absorption of tissue engineering
      cartilage. We transfected TGF-beta1 gene into bone marrow mesenchymal stem cells
      (BMMSCs) and co-cultured with interferon (IFN)-gamma and tumour necrosis factor
      (TNF)-alpha and CD4(+) CD25(-) T lymphocytes. We then characterized the
      morphological changes, apoptosis and characterization of chondrogenic-committed
      cells from TGF-beta1(+) BMMSCs and explored their mechanisms. Results showed that
      BMMSCs apoptosis and tissue engineering cartilage absorption in the group with
      added IFN-gamma and TNF-alpha were greater than in the control group. In
      contrast, there was little BMMSC apoptosis and absorption by tissue engineering
      cartilage in the group with added CD4(+) CD25(-) T lymphocytes; Foxp3(+) T cells
      and CD25(+) CD39(+) T cells were found. In contrast, no type II collagen or
      Foxp3(+) T cells or CD25(+) CD39(+) T cells was found in the TGF-beta1(-) BMMSC
      group. The data suggest that IFN-gamma and TNF-alpha induced BMMSCs apoptosis and
      absorption of tissue engineering cartilage, but the newborn regulatory T (Treg)
      cells inhibited the function of IFN-gamma and TNF-alpha and protected BMMSCs and
      tissue engineering cartilage. TGF-beta1not only played a cartilage inductive
      role, but also inhibited the absorption of tissue engineering cartilage. The
      pathway proposed in our study may simulate the actual reaction procedure after
      implantation of BMMSCs and tissue engineering cartilage in vivo.

PMID- 23868874
TI  - A high-throughput assay for frataxin allows for newborn screening, diagnosis, and
      treatment monitoring of Friedreich ataxia.

PMID- 23868875
TI  - STAT5b in LGL leukemia--a novel therapeutic target?

PMID- 23868876
TI  - Evidence for gender-specific endophenotypes in high-functioning autism spectrum
      disorder during empathy.
AB  - Despite remarkable behavioral gender differences in patients with autism spectrum
      disorder (ASD), and growing evidence for a diminished male : female ratio for the
      putative "male disorder" ASD, aspects of gender are not addressed accordingly in
      ASD research. Our study aims at filling this gap by exploring empathy abilities
      in a group of 28 patients with high-functioning ASD and 28 gender-, age- and
      education-matched non-autistic subjects, for the first time by means of
      functional neuroimaging (fMRI). In an event-related fMRI paradigm, emotional
      ("E") and neutral ("N") video clips presented actors telling self-related short
      stories. After each clip, participants were asked to indicate their own emotion
      and its intensity as well as the emotion and intensity perceived for the actor.
      Behaviorally, we found significantly less empathic responses in the overall ASD
      group compared with non-autistic subjects, and inadequate emotion recognition for
      the neutral clips in the female ASD group compared with healthy women. Neurally,
      increased activation of the bilateral medial frontal gyrus was found in male
      patients compared with female patients, a pattern which was not present in the
      non-autistic group. Additionally, autistic women exhibited decreased activation
      of midbrain and limbic regions compared with non-autistic women, whereas there
      was no significant difference within the male group. While we did not find a
      fundamental empathic deficit in autistic patients, our data propose different
      ways of processing empathy in autistic men and women, suggesting stronger
      impairments in cognitive aspects of empathy/theory of mind for men, and
      alterations of social reciprocity for women.

PMID- 23868877
TI  - Highly pathogenic avian influenza A(H5N1) mutants transmissible by air are
      susceptible to human and animal neutralizing antibodies.
AB  - A laboratory-generated reassortant H5 hemagglutinin (HA)/influenza A(H1N1) strain
      containing 4 mutations in influenza A(H5N1) HA has become transmissible by air
      among mammals. Here, we constructed 15 influenza A(H5N1) pseudoviruses containing
      a single mutation or a combination of mutations and showed that the pseudoviruses
      were susceptible to neutralizing antibodies from patients with influenza A(H5N1)
      infection and from mice immunized with a vaccine containing the conserved HA1
      sequence of influenza A(H5N1). These results indicate that antibodies in patients
      currently infected by influenza A(H5N1) and antibodies induced by vaccines
      containing conserved sequences in HA1 of wild-type influenza A(H5N1) are highly
      effective in cross-neutralizing future influenza A(H5N1) mutants with airborne
      transmissibility, suggesting that human influenza pandemics caused by these
      influenza A(H5N1) variants can be prevented. 

PMID- 23868878
TI  - Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6
      19 years in the United States and factors affecting its acquisition.
AB  - BACKGROUND:  Data on the age-specific prevalence of Epstein-Barr virus (EBV)
      infection are relevant for determining when to administer a prophylactic vaccine.
      Comparison of demographic groups could identify factors associated with its
      acquisition. METHODS:  The National Health and Nutrition Examination Surveys
      (NHANES) examine a representative sample of the US population. Serum specimens
      from NHANES participants 6-19 years old were tested for EBV antibody by enzyme
      immunoassay (EIA). A random portion was also tested by indirect
      immunofluorescence (IFA). Prevalence estimates and risk-factor comparisons used
      demographic data and sampling weights in logistic regression models. RESULTS: 
      Serum specimens collected between 2003 and 2010 from 9338 individuals
      participating in NHANES were tested. The concordance between EIA and IFA findings
      was 96.7%. The overall age-adjusted EBV antibody prevalence declined from 72% in
      2003-2004 to 65% in 2009-2010 (P = .027). The prevalence in 2009-2010 by age
      group was as follows: 6-8 years, 50%; 9-11 years, 55%; 12-14 years, 59%; 15-17
      years, 69%; and 18-19 years, 89%. Within each race/ethnicity group, younger age,
      health insurance coverage, higher household income, and education level were
      significantly associated with a lower prevalence of EBV antibody. CONCLUSIONS: 
      The EBV antibody prevalence declined in US individuals aged 6-19 years from 2003
      2004 to 2009-2010, mainly because of the decrease among non-Hispanic white
      participants. The declining antibody prevalence over time and the consistently
      high observed prevalence among participants aged 12-19 years support broad use of
      EBV vaccine before 12 years of age.

PMID- 23868879
TI  - Nanovesicle-based bioelectronic nose for the diagnosis of lung cancer from human
      blood.
AB  - A human nose-mimetic diagnosis system that can distinguish the odor of a lung
      cancer biomarker, heptanal, from human blood is presented. Selective recognition
      of the biomarker is mimicked in the human olfactory system. A specific olfactory
      receptor recognizing the chemical biomarker is first selected through screening a
      library of human olfactory receptors (hORs). The selected hOR is expressed on the
      membrane of human embryonic kidney (HEK)-293 cells. Nanovesicles containing the
      hOR on the membrane are produced from these cells, and are then used for the
      functionalization of single-walled carbon nanotubes. This strategy allows the
      development of a sensitive and selective nanovesicle-based bioelectronic nose
      (NvBN). The NvBN is able to selectively detect heptanal at a concentration as low
      as 1 * 10(-14) m, a sufficient level to distinguish the blood of a lung cancer
      patient from the blood of a healthy person. In actual experiments, NvBN could
      detect an extremely small increase in the amount of heptanal from human blood
      plasma without any pretreatment processes. This result offers a rapid and easy
      method to analyze chemical biomarkers from human blood in real-time and to
      diagnose lung cancer. 

PMID- 23868880
TI  - Radiation dose to premature new-borns in the Belgian neonatal intensive care
      units.
AB  - In the neonatal intensive care units (NICU), premature new-borns may be exposed
      to important doses. Because of their increased radiosensitivity and longer life
      expectancy, dose optimisation is of importance. The present study aimed at
      evaluating the dose of the most common radiographs in the Belgian NICU. Entrance
      surface kerma (ESK) and kerma area product (KAP) were collected in 17 NICU (among
      19 in Belgium). Median ESK ranged from 13 to 172 uGy and from 8 to 117 uGy for
      chest and combined chest-abdomen radiographs, respectively; median KAP ranged
      from 1.4 to 14.2 mGy cm(2) and from 3.8 to 28.1 mGy cm(2) for chest and combined
      chest-abdomen radiographs, respectively. Those differences were due to large
      variations in the examination settings. Diagnostic reference levels (DRL) were
      set for chest and combined chest-abdomen radiographs. Though the radiograph dose
      was usually low, the cumulative dose per stay could be high. The wide,
      intercentre differences indicate that there is scope for dose reduction. The use
      of DRL should contribute to achieve this object. 

PMID- 23868881
TI  - Repetitive behavior and restricted interests in young children with autism:
      comparisons with controls and stability over 2 years.
AB  - Restricted, repetitive and stereotyped patterns of behavior, interests and
      activities [RRBs] are among the core symptoms of autism spectrum disorders (ASD).
      Previous studies have indicated that RRBs differentiate ASD from other
      developmental disorders and from typical development. This study examined the
      presentation of RRBs as reported on the Repetitive Behavior Scale-Revised, a
      caregiver report, in children with ASD [separated into autism and Pervasive
      Developmental Disorder-Not Otherwise Specified groups] compared with children
      with nonspectrum developmental delays or typical development. We examined the
      role of age, cognitive functioning, sex and social communication impairment as
      they relate to RRBs. The stability of RRBs in children with autism was also
      examined over the course of 2 years. Results of the study confirmed that the
      amount and type of RRBs differs by diagnosis. Age, cognitive functioning, sex and
      social-communication impairment were not significant correlates. Among children
      with autism, RRBs remained stable over time.

PMID- 23868883
TI  - Screening and long-term retrospection for psychoactive drugs in presumptive drug
      facilitated crimes using segmented single hairs.

PMID- 23868884
TI  - Case report: quetiapine and refractory hypotension during general anesthesia in
      the operating room.
AB  - Quetiapine is an atypical antipsychotic with known alpha-adrenergic antagonism.
      We present a case of refractory hypotension that occurred after induction of
      general anesthesia in a patient being treated with quetiapine. This patient was
      not currently taking antihypertensives and had no known cardiovascular
      abnormalities. We observed that the hypotension was most responsive to
      vasopressin. We recommend further investigation regarding the interaction of
      quetiapine and general anesthesia. 

PMID- 23868885
TI  - Brief report: pulmonary auscultation in the operating room: a prospective
      randomized blinded trial comparing electronic and conventional stethoscopes.
AB  - BACKGROUND: We compared the subjective quality of pulmonary auscultation between
      2 acoustic stethoscopes (Holtex Ideal(r) and Littmann Cardiology III(r)) and an
      electronic stethoscope (Littmann 3200(r)) in the operating room. METHODS: A
      prospective double-blind randomized study with an evaluation during mechanical
      ventilation was performed in 100 patients. After each examination, the listeners
      using a numeric scale (0-10) rated the quality of auscultation. Auscultation
      quality was compared in patients among stethoscopes with a multilevel mixed
      effects linear regression with random intercept (operator effect), adjusted on
      significant factors in univariate analysis. A significant difference was defined
      as P < 0.05. RESULTS: One hundred comparative evaluations of pulmonary
      auscultation were performed. The quality of auscultation was rated 8.2 +/- 1.6
      for the electronic stethoscope, 7.4 +/- 1.8 for the Littmann Cardiology III, and
      4.6 +/- 1.8 for the Holtex Ideal. Compared with Holtex Ideal, auscultation
      quality was significantly higher with other stethoscopes (P < 0.0001). Compared
      with Littmann Cardiology III, auscultation quality was significantly higher with
      Littmann 3200 electronic stethoscope (beta = 0.9 [95% confidence interval, 0.5
      1.3]). CONCLUSIONS: An electronic stethoscope can provide a better quality of
      pulmonary auscultation than acoustic stethoscopes in the operating room, yet with
      a magnitude of improvement marginally higher than that provided with a high
      performance acoustic stethoscope. Whether this can translate into a clinically
      relevant benefit requires further studies.

PMID- 23868886
TI  - Focused review: spinal anesthesia in severe preeclampsia.
AB  - Spinal anesthesia is widely regarded as a reasonable anesthetic option for
      cesarean delivery in severe preeclampsia, provided there is no indwelling
      epidural catheter or contraindication to neuraxial anesthesia. Compared with
      healthy parturients, those with severe preeclampsia experience less frequent,
      less severe spinal-induced hypotension. In severe preeclampsia, spinal anesthesia
      may cause a higher incidence of hypotension than epidural anesthesia; however,
      this hypotension is typically easily treated and short lived and has not been
      linked to clinically significant differences in outcomes. In this review, we
      describe the advantages and limitations of spinal anesthesia in the setting of
      severe preeclampsia and the evidence guiding intraoperative hemodynamic
      management. 

PMID- 23868887
TI  - Trans-resectoscope stimulation predicts the need to block adductor response
      during bladder tumor resection.
AB  - BACKGROUND: Obturator nerve block is performed on patients who undergo
      transurethral resection of inferolateral bladder tumors to prevent thigh adductor
      muscle contraction. However, other than the tumor site, we have no criteria to
      judge whether this block is necessary in all patients. Moreover, it is difficult
      to predict the efficacy of obturator nerve block before resection. To solve these
      problems, we have devised a trans-resectoscope stimulation technique that
      involves delivering several single-twitch electrical stimuli to the inside wall
      of the bladder via a resectoscope to elicit contraction of the thigh adductor
      muscle. METHODS: Trans-resectoscope stimulation was performed in 51 cases on 45
      patients for which urologists had requested obturator nerve block. If no thigh
      adductor muscle contraction was observed with trans-resectoscope stimulation
      (i.e., negative result), tumor resection was performed without further
      investigation. If the result was positive, we performed obturator nerve block or
      administered a muscle relaxant until the result turned negative. Positive or
      negative responses to the initial trans-resectoscope stimulation and thigh
      adductor muscle contraction during subsequent resection were recorded. RESULTS:
      The initial trans-resectoscope stimulation result was negative in 29 of the 51
      cases (57%). In these cases, tumor resection was allowed to proceed, and no thigh
      adductor muscle contraction occurred (rate of incidence [95% confidence
      interval]: 0% [0%-5.7%]). In cases with a positive initial trans-resectoscope
      stimulation result (22/51 or 43%), we performed an obturator nerve block or
      administered a muscle relaxant after which we once again stimulated to verify the
      lack of adductor response before proceeding with the resection, and no thigh
      adductor muscle contraction was observed during resection. CONCLUSIONS: Trans
      resectoscope stimulation is beneficial not only to predict the need to block the
      contraction of the thigh adductor during tumor resection but also to avoid
      unnecessary obturator nerve block.

PMID- 23868888
TI  - Glucose use in fasted rats under sevoflurane anesthesia and propofol anesthesia.
AB  - BACKGROUND: We previously reported the marked differences in the effects of
      sevoflurane anesthesia and propofol anesthesia on glucose use in fed rats;
      however, we could not elucidate mechanisms underlying the differences. METHODS:
      We used fasted rats in this study. After surgical preparation under sevoflurane
      anesthesia, rats were divided into 3 groups: awake rats, rats under sevoflurane
      anesthesia, and rats under propofol anesthesia. All rats underwent the IV glucose
      tolerance test (IVGTT); 0.5 g/kg glucose was administered IV to rats. Just before
      IVGTT, some rats were pretreated with glibenclamide or diazoxide. We measured
      glucose, insulin, tumor necrosis factor-alpha (TNF-alpha), and high molecular
      weight adiponectin levels during IVGTT and calculated the quantitative insulin
      sensitivity check index (QUICKI) using glucose and insulin levels before glucose
      administration in each rat. RESULTS: Before glucose administration, rats under
      sevoflurane anesthesia showed similar glucose and insulin levels with
      significantly higher QUICKI compared with awake rats, while rats under propofol
      anesthesia showed similar glucose levels and significantly higher insulin levels
      with significantly lower QUICKI compared with awake rats. After glucose
      administration, rats under sevoflurane anesthesia showed significantly higher
      glucose levels and similar insulin levels compared with awake rats, while rats
      under propofol anesthesia showed similar glucose levels and significantly higher
      insulin levels compared with awake rats. Before glucose administration, TNF-alpha
      levels in rats under sevoflurane anesthesia and rats under propofol anesthesia
      were similar to those in awake rats. After glucose administration, TNF-alpha was
      undetectable in all awake rats and all rats under sevoflurane anesthesia, whereas
      TNF-alpha was detectable in all rats under propofol anesthesia; TNF-alpha levels
      in rats under propofol anesthesia were significantly higher than those in awake
      rats. High molecular weight adiponectin levels in rats under sevoflurane
      anesthesia and rats under propofol anesthesia were similar to those in awake rats
      throughout the experimental period. In rats under sevoflurane anesthesia,
      glibenclamide significantly decreased glucose levels and significantly increased
      insulin levels; however, diazoxide produced no significant effects on glucose and
      insulin levels. In rats under propofol anesthesia, glibenclamide significantly
      decreased glucose levels and significantly increased insulin levels, while
      diazoxide significantly decreased glucose levels without changing insulin levels.
      CONCLUSIONS: Sevoflurane anesthesia attenuates glucose-induced insulin secretion
      without affecting basic insulin secretion, while propofol anesthesia enhances
      insulin secretion. Propofol anesthesia exaggerates insulin-resistive conditions,
      whereas sevoflurane anesthesia dose not impair insulin sensitivity; there may be
      a possible association of TNF-alpha with insulin-resistive conditions under
      propofol anesthesia.

PMID- 23868889
TI  - The relationship between neuraxial anesthesia and advanced ovarian cancer-related
      outcomes in the Chilean population.
AB  - BACKGROUND: Mixed evidence has been published relating the use of regional
      anesthesia during oncologic surgery to a decrease in time to cancer recurrence
      and improvement in overall survival. We investigated whether the use of epidural
      anesthesia, in addition to general analgesia during and/or after surgical removal
      of advanced ovarian cancer, has an impact on time to recurrence and overall
      survival. METHODS: Patients were identified from a prospective clinical registry.
      Eighty patients with advanced ovarian cancer (International Federation of
      Gynecologists and Obstetricians, stage IIIC and IV) undergoing surgery between
      January 2000 and March 2011 were studied. Propensity scoring (PS) methods
      (matching and inverse weighting) were used to compare the time to recurrence and
      overall survival of patients who did and did not receive epidural anesthesia
      and/or analgesia (EA), after controlling for selection bias. RESULTS: The median
      time to recurrence was 1.6 and 0.9 years for the EA and no EA groups,
      respectively (P = 0.02). After PS matching, the median time to recurrence was 1.6
      and 1.4 years for the EA and no EA groups, respectively (P = 0.30). Similarly, PS
      weighting did not demonstrate an improvement in time to recurrence with the use
      of EA. Using a Cox proportional hazards model in the PS-matched sample, the
      estimated hazard ratio for EA exposure (0.72; 95% confidence interval [CI], 0.40
      1.33) did not change substantially after adjusting for chemotherapy (0.73; 95%
      CI, 0.40-1.31). Similar results were obtained using PS weighting. The median
      survival time was 3.3 and 1.9 years for the EA and no EA groups, respectively (P
      = 0.01). After PS matching, the median survival time was 3.3 and 2.7 years for
      the EA and no EA groups, respectively (P = 0.37). Similarly, PS weighting did not
      demonstrate an improved survival with the use of EA. The estimated hazard ratio
      (0.74; 95% CI, 0.36-1.49) in the PS matched sample did not change substantially
      after adjusting for chemotherapy, with similar results when PS weighting was
      applied. CONCLUSIONS: After PS matching and weighting, we found no benefit in
      overall survival or time to recurrence in patients with advanced stages
      (International Federation of Gynecologists and Obstetricians IIIC and IV) of
      ovarian cancer after the use of EA during and after tumor debulking surgery.

PMID- 23868890
TI  - The effectiveness of a perioperative smoking cessation program: a randomized
      clinical trial.
AB  - BACKGROUND: Cigarette smoking by surgical patients is associated with increased
      complications, particularly perioperative respiratory problems and poor wound
      healing. In this study, we sought to determine whether a pragmatic perioperative
      smoking cessation intervention designed for a busy preadmission clinic would be
      successful in reducing smoking rates and intraoperative and immediate
      postoperative complications. METHODS: This randomized controlled trial was
      conducted at a university-affiliated hospital in London, Ontario, Canada.
      Patients seen in the preadmission clinic at least 3 weeks preoperatively were
      randomized to either the control group (84 patients) or the intervention group
      (84 patients). The control group received no specific smoking cessation
      intervention. The intervention group received (1) brief counseling by the
      preadmission nurse, (2) brochures on smoking cessation, (3) referral to the
      Canadian Cancer Society's Smokers' Helpline, and (4) a free 6-week supply of
      transdermal nicotine replacement therapy. All outcome assessors and caregivers on
      the operative day were blinded to group assignment. The primary outcome was the
      rate of smoking cessation as confirmed by exhaled carbon monoxide breath test.
      Secondary outcomes included perioperative complications and smoking status at 30
      days postoperatively. RESULTS: Between October 2010 and April 2012, 168 patients
      were recruited into the study. Smoking cessation occurred in 12 patients (14.3%)
      in the intervention group as compared with 3 patients (3.6%) in the control group
      (relative risk 4.0; 95% confidence interval [CI], 1.2-13.7; P = 0.03). The
      overall rate of combined intraoperative and immediate postoperative complications
      was not significantly different between intervention and control groups (13.1%
      and 16.7%, respectively; relative risk 0.79; 95% CI, 0.38-1.63; P = 0.67). At
      follow-up 30 days postoperatively, smoking cessation was reported in 22 patients
      (28.6%) in the intervention group compared with 8 patients (11%) in controls
      (relative risk 2.6; 95% CI, 1.2-5.5; P = 0.008). CONCLUSIONS: One of the
      objections to widespread use of smoking cessation interventions in the
      preadmission clinic is that it is too labor-intensive. The results of this study
      show that a smoking cessation intervention, designed to minimize additional use
      of physician or nursing time, results in decreased smoking rates on the day of
      surgery and promotes abstinence 30 days postoperatively.

PMID- 23868891
TI  - Computational analysis of the effects of reduced temperature on thrombin
      generation: the contributions of hypothermia to coagulopathy.
AB  - BACKGROUND: Hypothermia, which can result from tissue hypoperfusion, body
      exposure, and transfusion of cold resuscitation fluids, is a major factor
      contributing to coagulopathy of trauma and surgery. Despite considerable efforts,
      the mechanisms of hypothermia-induced blood coagulation impairment have not been
      fully understood. We introduce a kinetic modeling approach to investigate the
      effects of hypothermia on thrombin generation. METHODS: We extended a validated
      computational model to predict and analyze the impact of low temperatures (with
      or without concomitant blood dilution) on thrombin generation and its
      quantitative parameters. The computational model reflects the existing knowledge
      about the mechanistic details of thrombin generation biochemistry. We performed
      the analysis for an "average" subject, as well as for 472 subjects in the control
      group of the Leiden Thrombophilia Study. RESULTS: We computed and analyzed
      thousands of kinetic curves characterizing the generation of thrombin and the
      formation of the thrombin-antithrombin complex (TAT). In all simulations,
      hypothermia in the temperature interval 31 degrees C to 36 degrees C
      progressively slowed down thrombin generation, as reflected by clotting time,
      thrombin peak time, and prothrombin time, which increased in all subjects (P <
      10(-5)). Maximum slope of the thrombin curve was progressively decreased, and the
      area under the thrombin curve was increased in hypothermia (P < 10(-5)); thrombin
      peak height remained practically unaffected. TAT formation was noticeably delayed
      (P < 10(-5)), but the final TAT levels were not significantly affected.
      Hypothermia-induced fold changes in the affected thrombin generation parameters
      were larger for lower temperatures, but were practically independent of the
      parameter itself and of the subjects' clotting factor composition, despite
      substantial variability in the subject group. Hypothermia and blood dilution
      acted additively on the thrombin generation parameters. CONCLUSIONS: We developed
      a general computational strategy that can be used to simulate the effects of
      changing temperature on the kinetics of biochemical systems and applied this
      strategy to analyze the effects of hypothermia on thrombin generation. We found
      that thrombin generation can be noticeably impaired in subjects with different
      blood plasma composition even in moderate hypothermia. Our work provides
      mechanistic support to the notion that thrombin generation impairment may be a
      key factor in coagulopathy induced by hypothermia and complicated by blood plasma
      dilution.

PMID- 23868892
TI  - Echo rounds: intraoperative transesophageal echocardiography of a left atrial
      mass after total artificial heart implantation.

PMID- 23868893
TI  - Brief report: leaking esophageal probe may lead to false ventilator settings when
      guiding positive end-expiratory pressure by transpulmonary pressure.
AB  - Esophageal pressure (Pes) is a surrogate for intrapleural pressure. Measuring Pes
      during mechanical ventilation allows for positive end-expiratory pressure
      adjustments by transpulmonary pressure (PL), which has been shown to improve
      oxygenation and outcome in acute respiratory distress syndrome patients. In
      morbidly obese patients, we saw progressively increasing PL measurements,
      although airway pressure (Paw), intra-abdominal pressure, and patient position
      did not change. On further examination, we determined that the gradual increases
      of PL were artifacts caused by a leak in the pressure probes, which resulted in
      underestimation of Pes and overestimation of PL as derived from the equation Paw 
      Pes = PL. 

PMID- 23868894
TI  - The myotoxic effect of bupivacaine and ropivacaine on myotubes in primary mouse
      cell culture and an immortalized cell line.
AB  - BACKGROUND: The 2 local anesthetics (LAs) bupivacaine and ropivacaine have acute
      cytotoxic effects on different tissues. In this respect, LA-induced myotoxicity
      has been subject to various studies; however, the exact mechanisms are still not
      fully understood. Most in vitro studies use immortalized cell lines because of
      feasibility. Thus, establishing a primary cell line might result in more accurate
      results. In this study, we examined the effects of immortalization on bupivacaine
      and ropivacaine-induced myotoxicity in vitro. METHODS: An immortalized (N = 6)
      and a primary cell line (N = 8) of the same tissue and species were established,
      and differentiation in myotubes was induced. Cells were exposed to increasing
      concentrations of bupivacaine and ropivacaine for 1 or 2 hours, respectively.
      Twenty-four and 48 hours after treatment, the fractions of dead and vital cells
      were measured using flow cytometry. Significance was tested through 1-way
      analysis of variance with post hoc Dunnett T3 test. Medians of dataset pairs were
      compared by T test. RESULTS: In both cell lines, increasing concentrations of
      both LAs resulted in decreased cell survival (e.g., P < 0.001 for 5000 ppm
      bupivacaine, 1 or 2 hours of incubation, and 24 hours recovery in both cell
      lines). For the same LA concentrations, survival was significantly higher in the
      immortalized cell culture (e.g., P < 0.001 for 2500 ppm ropivacaine, 1 hour of
      incubation, and 24 hours recovery). In addition, equal concentrations of
      bupivacaine resulted in significantly fewer vital cells compared with ropivacaine
      (e.g., P = 0.032 for 2500 ppm ropivacaine, 1 hour of incubation, and 24 hours
      recovery). Two hours of incubation resulted in a significantly higher rate of
      dead cells compared with 1 hour of incubation (e.g., P = 0.004 for C2C12 cells,
      2500 ppm bupivacaine, and 24 hours recovery). CONCLUSIONS: Primary skeletal
      muscle cells are more vulnerable to LAs than immortalized cells. The higher
      myotoxic potential of bupivacaine compared with ropivacaine in vivo can be
      reproduced in vitro. Incubation time has an influence on cell survival.

PMID- 23868895
TI  - Endobronchial lesion due to pulmonary Fusobacterium nucleatum infection in a
      child.
AB  - Clinically significant infections due to the members of the genus Fusobacterium
      are rare. The clinical manifestations of pulmonary Fusobacterium nucleatum
      infections range from simple aspiration pneumonia to severe diseases as
      necrotizing pneumonia, lung abscess, and empyema. Endobronchial lesions and
      obstructions are rarely seen in children and are often a misdiagnosed result in
      delay of definitive treatment. Here, we report a case of endobronchial lesion due
      to pulmonary F. nucleatum infection in an entirely healthy child before illness.
      This is the first case reported in the literature of endobronchial lesion due to
      pulmonary F. nucleatum infection.

PMID- 23868896
TI  - Disgust regulation via placebo: an fMRI study.
AB  - The present fMRI study investigated whether placebo treatment can change disgust
      feelings. Disgust-prone women underwent a retest design where they were presented
      with disgusting, fear-eliciting and neutral pictures once with and once without a
      placebo (inert pill presented with the suggestion that it can reduce disgust
      symptoms). The placebo provoked a strong decrease of experienced disgust, which
      was accompanied by reduced insula activation. Exploratory psychophysiological
      interaction analyses revealed decreased connectivity in a network consisting of
      the insula, the amygdala, the anterior cingulate cortex and the orbitofrontal
      cortex. Moreover, the placebo increased amygdala-DMPFC coactivation. Our findings
      suggest that placebo use can modulate a specific affective state and might be an
      option as a first therapy step for clinical samples characterized by excessive
      and difficult-to-control disgust feelings. 

PMID- 23868897
TI  - Assessing the impact of national guidelines on the management of children
      hospitalized for acute bronchiolitis.
AB  - BACKGROUND: Acute bronchiolitis is a common illness accounting for $500 million
      annually in hospitalizations. Despite the frequency of bronchiolitis, its
      diagnosis and management is variable. To address this variability, the American
      Academy of Pediatrics (AAP) published an evidence-based practice management
      guideline for bronchiolitis in 2006. OBJECTIVE: Assess for changes in physician
      behavior in the management of bronchiolitis before and after publication of the
      2006 AAP bronchiolitis guideline. METHODS: A retrospective chart review was
      performed at two academic medical centers of children <24 months of age admitted
      to the hospital with a primary or secondary discharge diagnosis of bronchiolitis.
      Pre-guideline charts were gathered from 2004 to 2005 and post-guideline charts
      from 2007 to 2008. Evaluation and therapeutic interventions prior to and during
      hospitalization were analyzed. Data were analyzed using chi-squared analysis for
      categorical variables, Mann-Whitney testing for continuous variables. RESULTS:
      One thousand two hundred thirty-three patients met inclusion criteria. Diagnostic
      laboratory testing rates did not decline after guideline publication. The number
      of chest X-rays obtained decreased from 72.9% to 66.7% post-guidelines (P =
      0.02). Fewer children received a trial of racemic epinephrine (17.8% vs. 12.2%, P
      = 0.006) or albuterol (81.6% vs. 72.6%, P < 0.0001) post-guidelines, and
      physicians more often discontinued albuterol when documented ineffective in the
      post-guidelines period (28.6% vs. 78.9%, P < 0.0001). Corticosteroid use in
      children without a history of RAD or asthma dropped post-guidelines (26.5% vs.
      17.5%, P < 0.0001). CONCLUSIONS: A modest change in physician behavior in the
      inpatient management of bronchiolitis was seen post-guidelines. Additional health
      care provider training and education is warranted to reduce unnecessary
      interventions and healthcare resources use.

PMID- 23868899
TI  - AKI: a path forward.
AB  - The Kidney Research National Dialogue, supported by the National Institute of
      Diabetes and Digestive and Kidney Diseases, asked the scientific community to
      formulate and prioritize research objectives that would improve our understanding
      of kidney function and disease. High-priority objectives for AKI were identified,
      including enhancing training and collaborative opportunities, improving
      phenotyping and development of clinical tools, expanding our understanding of the
      pathophysiology and interaction between injury and reparative processes, and
      identifying determinants of long-term outcomes. Research in animal models must be
      translated to improve diagnosis and treatment of patients. The objectives
      identified by the Kidney Research National Dialogue provide the research
      community with future opportunities for improving the prevention, diagnosis, and
      treatment of people with AKI. 

PMID- 23868898
TI  - Kidney disease and multiple myeloma.
AB  - Kidney injury is a common complication of multiple myeloma and other plasma cell
      dyscrasias, and it is associated with increased mortality. Multiple pathogenic
      mechanisms can contribute to kidney injury in the patient with myeloma, some of
      which are the result of nephrotoxic monoclonal Ig and some of which are
      independent of paraprotein deposition. The pathogenic mechanisms that underlie
      paraprotein-related kidney disease are increasingly well understood. A novel
      assay allowing the quantification of free light chains in the serum has aided the
      diagnosis of new onset disease and allowed for the earlier detection of relapse.
      Novel myeloma agents have shown considerable promise in reversing renal failure
      in some patients and improving outcomes. Stem cell transplantation remains a
      mainstay of management for younger patients with myeloma who are suitable
      candidates for intensive therapy, whereas the role of new drugs, plasma exchange,
      and kidney transplantation continues to evolve. 

PMID- 23868900
TI  - Beyond the futility argument: the fair process approach and time-limited trials
      for managing dialysis conflict.
AB  - Futility is an ancient concept arising from Greek mythology that was resurrected
      for its medical application in the 1980s with the proliferation of many
      lifesaving technologies, including dialysis and renal transplantation. By that
      time, the domineering medical paternalism that characterized the pre-1960s
      physician-patient relationship morphed into assertive patient autonomy, and some
      patients began to claim the right to demand aggressive, high-technology
      interventions, despite physician disapproval. To counter this power struggle, the
      establishment of a precise definition of futility offered hope for a futility
      policy that would allow physicians to justify withholding or withdrawing
      treatment, despite patient and family objections. This article reviews the
      various attempts made to define medical futility and describes their limited
      applicability to dialysis. When futility concerns arise, physicians should
      recognize the opportunity to address conflict, using best practice communication
      skills. Physicians would also benefit from understanding the ethical principles
      of respect for patient autonomy, beneficence, nonmaleficence, justice, and
      professional integrity that underlie medical decision-making. Also reviewed is
      the use of a fair process approach or time-limited trial when conflict resolution
      cannot be achieved. These topics are addressed in the Renal Physician
      Association's clinical practice guideline Shared Decision-Making in the
      Appropriate Initiation and Withdrawal from Dialysis, with which nephrologists
      should be well versed. A case presentation of intractable calciphylaxis in a new
      dialysis patient illustrates the pitfalls of physicians not fully appreciating
      the ethics of medical decision-making and failing to use effective conflict
      management approaches in the clinical practice guideline. 

PMID- 23868901
TI  - Dabigatran and kidney disease: a bad combination.
AB  - Dabigatran is an oral direct thrombin inhibitor widely used to prevent and treat
      various thromboembolic complications. An advantage of this agent over other
      anticoagulants is that routine laboratory monitoring and related dose adjustments
      are considered unnecessary. A major disadvantage is the absence of a reliable
      means of reversing its anticoagulant effect. After U.S. Food and Drug
      Administration approval, recently emerged data suggest a higher bleeding risk
      with dabigatran, especially in the elderly. Clinicians are thus faced with caring
      for patients with serious bleeding events without readily available tests to
      measure drug levels or the anticoagulant effects of dabigatran and without
      effective antidotes to rapidly reverse the anticoagulant effect. On the basis of
      dabigatran's pharmacokinetic profile, hemodialysis and continuous renal
      replacement therapy have been used to remove dabigatran with the hope, still
      unproven, that this would rapidly reverse the anticoagulant effect and reduce
      bleeding in patients with normal and those with reduced kidney function. However,
      the best clinical approach to the patient with serious bleeding is not known, and
      the risks of placing a hemodialysis catheter in an anticoagulated patient can be
      substantial. This article reviews this issue, addressing clinical indications,
      drug pharmacokinetics, clinical and laboratory monitoring tests, and dialytic and
      nondialytic approaches to reduce bleeding in dabigatran-treated patients. 

PMID- 23868902
TI  - Prevalence of apparent treatment-resistant hypertension among individuals with
      CKD.
AB  - BACKGROUND AND OBJECTIVES: Apparent treatment-resistant hypertension is defined
      as systolic/diastolic BP >= 140/90 mmHg with concurrent use of three or more
      antihypertensive medication classes or use of four or more antihypertensive
      medication classes regardless of BP level. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: The prevalence of apparent treatment-resistant hypertension among
      Reasons for Geographic and Racial Differences in Stroke study participants
      treated for hypertension (n=10,700) was determined by level of estimated GFR and
      albumin-to-creatinine ratio, and correlates of apparent treatment-resistant
      hypertension among those participants with CKD were evaluated. CKD was defined as
      an albumin-to-creatinine ratio >= 30 mg/g or estimated GFR<60 ml/min per 1.73
      m(2). RESULTS: The prevalence of apparent treatment-resistant hypertension was
      15.8%, 24.9%, and 33.4% for those participants with estimated GFR >= 60, 45-59,
      and <45 ml/min per 1.73 m(2), respectively, and 12.1%, 20.8%, 27.7%, and 48.3%
      for albumin-to-creatinine ratio<10, 10-29, 30-299, and >= 300 mg/g, respectively.
      The multivariable-adjusted prevalence ratios (95% confidence intervals) for
      apparent treatment-resistant hypertension were 1.25 (1.11 to 1.41) and 1.20 (1.04
      to 1.37) for estimated GFR levels of 45-59 and <45 ml/min per 1.73 m(2),
      respectively, versus >= 60 ml/min per 1.73 m(2) and 1.54 (1.39 to 1.71), 1.76
      (1.57 to 1.97), and 2.44 (2.12 to 2.81) for albumin-to-creatinine ratio levels of
      10-29, 30-299, and >= 300 mg/g, respectively, versus albumin-to-creatinine
      ratio<10 mg/g. After multivariable adjustment, men, black race, larger waist
      circumference, diabetes, history of myocardial infarction or stroke, statin use,
      and lower estimated GFR and higher albumin-to-creatinine ratio levels were
      associated with apparent treatment-resistant hypertension among individuals with
      CKD. CONCLUSIONS: This study highlights the high prevalence of apparent treatment
      resistant hypertension among individuals with CKD.

PMID- 23868903
TI  - Late recurrence of nonseminomatous germ cell tumor successfully treated with
      intensity-modulated radiation therapy.
AB  - We report the case of a 41-year-old man with a late recurrence of nonseminomatous
      germ cell tumor, which was successfully treated with intensity-modulated
      radiation therapy. For the residual retrocrural tumor invading the 11th and 12th
      thoracic vertebrae with an abnormal level of tumor marker (alpha-fetoprotein:
      23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due
      to its neurotoxicity, and surgery could not be performed due to the location. In
      this situation, intensity-modulated radiation therapy achieved a complete
      response of tumor marker. The patient remained in complete clinical remission
      after 3 years. The efficacy of radiotherapy, especially intensity-modulated
      radiation therapy, for a nonseminomatous germ cell tumor is discussed. 

PMID- 23868904
TI  - Striving to improve patient-reported outcomes for cancer survivors as the war
      wages on.

PMID- 23868905
TI  - Health-related quality-of-life assessment in CLEOPATRA, a phase III study
      combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer.
AB  - BACKGROUND: The phase III CLEOPATRA study demonstrated that combining pertuzumab
      with trastuzumab plus docetaxel significantly improves progression-free and
      overall survival in previously untreated HER2-positive metastatic breast cancer.
      Here, we report health-related quality-of-life (HRQoL) results from CLEOPATRA.
      PATIENTS AND METHODS: Participants were randomly assigned to pertuzumab or
      placebo, each given with trastuzumab plus docetaxel every 3 weeks. Pertuzumab and
      trastuzumab were administered until progression and six or more docetaxel cycles
      were recommended. Time from randomization to a >= 5-point decrease in Trial
      Outcome Index-Physical/Functional/Breast (TOI-PFB) of the Functional Assessment
      of Cancer Therapy-Breast (FACT-B) questionnaire was analyzed as a prespecified
      secondary end point. A post hoc exploratory analysis investigated time to >= 2
      point deterioration in Breast Cancer Subscale (BCS) score. RESULTS: Time to >= 5
      point decline in TOI-PFB did not differ significantly between the pertuzumab and
      placebo arms [hazard ratio (HR), 0.97; P = 0.7161]. The median times to TOI-PFB
      deterioration were 18.4 and 18.3 weeks, respectively (approximately six cycles).
      The mean TOI-PFB declined slightly until week 18 and recovered thereafter.
      Pertuzumab increased time until BCS deterioration versus placebo (median 26.7
      versus 18.3 weeks; HR, 0.77; P = 0.0061). CONCLUSIONS: Combining pertuzumab with
      trastuzumab and docetaxel had no adverse impact on HRQoL and may prolong time to
      worsening of breast cancer-specific symptoms.

PMID- 23868906
TI  - Primary cutaneous lymphomas: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 23868907
TI  - Results of a phase II pilot study of moderate dose radiotherapy for inoperable
      desmoid-type fibromatosis--an EORTC STBSG and ROG study (EORTC 62991-22998).
AB  - BACKGROUND: To determine the activity of radiotherapy in patients with inoperable
      desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was
      carried out. MATERIALS AND METHODS: Patients with inoperable progressive disease
      of primary, recurrent or incompletely resected lesions received a dose of 56 Gy
      in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2
      years and thereafter every 6 months. The primary end point was local control rate
      at 3 years, estimated by a nonparametric method for interval-censored survival
      data. Secondary end points were objective tumor response, acute and late toxic
      effect. RESULTS: Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008.
      Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and
      extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control
      rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall
      response during the first 3 years was complete response (CR) 6 (13.6%), partial
      response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%)
      and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years,
      the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side
      effects were limited to skin, mucosal membranes and pain. Late toxic effect
      consisted of mild edema in 10 patients. CONCLUSIONS: Moderate dose radiotherapy
      is an effective treatment of patients with DF. Response after radiation therapy
      is slow with continuing regression seen even after 3 years.

PMID- 23868908
TI  - CREDO: a structural interactomics database for drug discovery.
AB  - CREDO is a unique relational database storing all pairwise atomic interactions of
      inter- as well as intra-molecular contacts between small molecules and
      macromolecules found in experimentally determined structures from the Protein
      Data Bank. These interactions are integrated with further chemical and biological
      data. The database implements useful data structures and algorithms such as
      cheminformatics routines to create a comprehensive analysis platform for drug
      discovery. The database can be accessed through a web-based interface, downloads
      of data sets and web services at http://www-cryst.bioc.cam.ac.uk/credo. Database
      URL: http://www-cryst.bioc.cam.ac.uk/credo. 

PMID- 23868910
TI  - Plasma lipid profiling in a large population-based cohort.
AB  - We have performed plasma lipid profiling using liquid chromatography electrospray
      ionization tandem mass spectrometry on a population cohort of more than 1,000
      individuals. From 10 MUl of plasma we were able to acquire comparative measures
      of 312 lipids across 23 lipid classes and subclasses including sphingolipids,
      phospholipids, glycerolipids, and cholesterol esters (CEs) in 20 min. Using
      linear and logistic regression, we identified statistically significant
      associations of lipid classes, subclasses, and individual lipid species with
      anthropometric and physiological measures. In addition to the expected
      associations of CEs and triacylglycerol with age, sex, and body mass index (BMI),
      ceramide was significantly higher in males and was independently associated with
      age and BMI. Associations were also observed for sphingomyelin with age but this
      lipid subclass was lower in males. Lysophospholipids were associated with age and
      higher in males, but showed a strong negative association with BMI. Many of these
      lipids have previously been associated with chronic diseases including
      cardiovascular disease and may mediate the interactions of age, sex, and obesity
      with disease risk. 

PMID- 23868909
TI  - Multinational evidence-based recommendations for the diagnosis and management of
      gout: integrating systematic literature review and expert opinion of a broad
      panel of rheumatologists in the 3e initiative.
AB  - We aimed to develop evidence-based multinational recommendations for the
      diagnosis and management of gout. Using a formal voting process, a panel of 78
      international rheumatologists developed 10 key clinical questions pertinent to
      the diagnosis and management of gout. Each question was investigated with a
      systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts
      from 2010-2011 European League Against Rheumatism and American College of
      Rheumatology meetings were searched in each review. Relevant studies were
      independently reviewed by two individuals for data extraction and synthesis and
      risk of bias assessment. Using this evidence, rheumatologists from 14 countries
      (Europe, South America and Australasia) developed national recommendations. After
      rounds of discussion and voting, multinational recommendations were formulated.
      Each recommendation was graded according to the level of evidence. Agreement and
      potential impact on clinical practice were assessed. Combining evidence and
      clinical expertise, 10 recommendations were produced. One recommendation referred
      to the diagnosis of gout, two referred to cardiovascular and renal comorbidities,
      six focused on different aspects of the management of gout (including drug
      treatment and monitoring), and the last recommendation referred to the management
      of asymptomatic hyperuricaemia. The level of agreement with the recommendations
      ranged from 8.1 to 9.2 (mean 8.7) on a 1-10 scale, with 10 representing full
      agreement. Ten recommendations on the diagnosis and management of gout were
      established. They are evidence-based and supported by a large panel of
      rheumatologists from 14 countries, enhancing their utility in clinical practice. 

PMID- 23868911
TI  - Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2
      activity in Alzheimer's disease.
AB  - Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP)
      that are important in brain pathophysiology. We recruited cognitively healthy
      (CH), minimally cognitively impaired (MCI), and late onset Alzheimer's disease
      (LOAD) study participants and collected their CSF. After fractionation into
      nanometer particles (NP) and supernatant fluids (SF), we studied the lipid
      composition of these compartments. LC-MS/MS studies reveal that both CSF
      fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl
      sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC),
      1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids,
      and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a
      mixture of saturated, monounsaturated, and polyunsaturated fatty acid species,
      while PE and PS in the SF fractions are enriched with PUFA-containing molecular
      species. PC, PE, and PS levels in CSF fractions decrease progressively in
      participants from CH to MCI, and then to LOAD. Whereas most PC species decrease
      equally in LOAD, plasmalogen species account for most of the decrease in PE. A
      significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP
      decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer
      particles have different GP composition, and that PLA2 activity accounts for
      altered GPs in these fractions as neurodegeneration progresses. 

PMID- 23868912
TI  - Overlapping substrate and inhibitor specificity of human and murine ABCG2.
AB  - ABCG2 (also known as breast cancer resistance protein) is an ATP-binding cassette
      (ABC) transporter localized to the plasma membrane where it mediates the efflux
      of xenobiotics, including potential therapeutics. Studies investigating Abcg2
      function at the blood-brain barrier in mouse models are often compared with human
      ABCG2 function. It is critical to understand the nature of species differences
      between mouse and human ABCG2, since extrapolations are made from murine data to
      humans. Two independent drug-selected cell line pairs expressing human or mouse
      ABCG2 were compared for efflux of fluorescent substrates using flow cytometry. To
      this end, we developed and characterized a new mouse Abcg2-expressing subline
      that demonstrated efflux of known fluorescent ABCG2 substrates and increased
      resistance to mitoxantrone, which is reduced in the presence of the ABCG2
      inhibitor Ko143. Our results indicate that the substrate specificity of human and
      mouse ABCG2 is very similar. We identified a new human and mouse ABCG2 substrate,
      a porphyrin analog, purpurin-18 (Pp-18), which is not a substrate for P
      glycoprotein or multidrug resistance protein 1. The ability of inhibitors to
      block efflux activity of ABCG2 was assessed using Pp-18. Inhibitors also
      demonstrated similar effects on human and mouse ABCG2. Chrysin, benzoflavone, and
      cyclosporin A inhibited Pp-18 efflux in both human and mouse ABCG2. The
      similarity of the substrate and inhibitor specificity of human and mouse ABCG2
      supports interpretation of mouse models in understanding the clinical,
      pharmacological, and physiologic roles of ABCG2. 

PMID- 23868915
TI  - Long-term ventilation: charting a pathway home.

PMID- 23868916
TI  - Prevention of renal disease in Henoch-Schonlein purpura: clear evidence against
      steroids.

PMID- 23868913
TI  - Advances in osteoarthritis genetics.
AB  - Osteoarthritis (OA), the most common form of arthritis, is a highly debilitating
      disease of the joints and can lead to severe pain and disability. There is no
      cure for OA. Current treatments often fail to alleviate its symptoms leading to
      an increased demand for joint replacement surgery. Previous epidemiological and
      genetic research has established that OA is a multifactorial disease with both
      environmental and genetic components. Over the past 6 years, a candidate gene
      study and several genome-wide association scans (GWAS) in populations of Asian
      and European descent have collectively established 15 loci associated with knee
      or hip OA that have been replicated with genome-wide significance, shedding some
      light on the aetiogenesis of the disease. All OA associated variants to date are
      common in frequency and appear to confer moderate to small effect sizes. Some of
      the associated variants are found within or near genes with clear roles in OA
      pathogenesis, whereas others point to unsuspected, less characterised pathways.
      These studies have also provided further evidence in support of the existence of
      ethnic, sex, and joint specific effects in OA and have highlighted the importance
      of expanded and more homogeneous phenotype definitions in genetic studies of OA. 

PMID- 23868917
TI  - Imaging of the CO snow line in a solar nebula analog.
AB  - Planets form in the disks around young stars. Their formation efficiency and
      composition are intimately linked to the protoplanetary disk locations of "snow
      lines" of abundant volatiles. We present chemical imaging of the carbon monoxide
      (CO) snow line in the disk around TW Hya, an analog of the solar nebula, using
      high spatial and spectral resolution Atacama Large Millimeter/Submillimeter Array
      observations of diazenylium (N2H(+)), a reactive ion present in large abundance
      only where CO is frozen out. The N2H(+) emission is distributed in a large ring,
      with an inner radius that matches CO snow line model predictions. The extracted
      CO snow line radius of ~30 astronomical units helps to assess models of the
      formation dynamics of the solar system, when combined with measurements of the
      bulk composition of planets and comets.

PMID- 23868918
TI  - The hologenomic basis of speciation: gut bacteria cause hybrid lethality in the
      genus Nasonia.
AB  - Although the gut microbiome influences numerous aspects of organismal fitness,
      its role in animal evolution and the origin of new species is largely unknown.
      Here we present evidence that beneficial bacterial communities in the guts of
      closely related species of the genus Nasonia form species-specific phylosymbiotic
      assemblages that cause lethality in interspecific hybrids. Bacterial constituents
      and abundance are irregular in hybrids relative to parental controls, and
      antibiotic curing of the gut bacteria significantly rescues hybrid survival.
      Moreover, feeding bacteria to germ-free hybrids reinstates lethality and
      recapitulates the expression of innate immune genes observed in conventionally
      reared hybrids. We conclude that in this animal complex, the gut microbiome and
      host genome represent a coadapted "hologenome" that breaks down during
      hybridization, promoting hybrid lethality and assisting speciation. 

PMID- 23868919
TI  - Control of metal nanocrystal size reveals metal-support interface role for ceria
      catalysts.
AB  - Interactions between ceria (CeO2) and supported metals greatly enhance rates for
      a number of important reactions. However, direct relationships between structure
      and function in these catalysts have been difficult to extract because the
      samples studied either were heterogeneous or were model systems dissimilar to
      working catalysts. We report rate measurements on samples in which the length of
      the ceria-metal interface was tailored by the use of monodisperse nickel,
      palladium, and platinum nanocrystals. We found that carbon monoxide oxidation in
      ceria-based catalysts is greatly enhanced at the ceria-metal interface sites for
      a range of group VIII metal catalysts, clarifying the pivotal role played by the
      support. 

PMID- 23868920
TI  - Pluripotent stem cells induced from mouse somatic cells by small-molecule
      compounds.
AB  - Pluripotent stem cells can be induced from somatic cells, providing an unlimited
      cell resource, with potential for studying disease and use in regenerative
      medicine. However, genetic manipulation and technically challenging strategies
      such as nuclear transfer used in reprogramming limit their clinical applications.
      Here, we show that pluripotent stem cells can be generated from mouse somatic
      cells at a frequency up to 0.2% using a combination of seven small-molecule
      compounds. The chemically induced pluripotent stem cells resemble embryonic stem
      cells in terms of their gene expression profiles, epigenetic status, and
      potential for differentiation and germline transmission. By using small
      molecules, exogenous "master genes" are dispensable for cell fate reprogramming.
      This chemical reprogramming strategy has potential use in generating functional
      desirable cell types for clinical applications. 

PMID- 23868921
TI  - Positive feedback between PU.1 and the cell cycle controls myeloid
      differentiation.
AB  - Regulatory gene circuits with positive-feedback loops control stem cell
      differentiation, but several mechanisms can contribute to positive feedback.
      Here, we dissect feedback mechanisms through which the transcription factor PU.1
      controls lymphoid and myeloid differentiation. Quantitative live-cell imaging
      revealed that developing B cells decrease PU.1 levels by reducing PU.1
      transcription, whereas developing macrophages increase PU.1 levels by lengthening
      their cell cycles, which causes stable PU.1 accumulation. Exogenous PU.1
      expression in progenitors increases endogenous PU.1 levels by inducing cell cycle
      lengthening, implying positive feedback between a regulatory factor and the cell
      cycle. Mathematical modeling showed that this cell cycle-coupled feedback
      architecture effectively stabilizes a slow-dividing differentiated state. These
      results show that cell cycle duration functions as an integral part of a positive
      autoregulatory circuit to control cell fate. 

PMID- 23868923
TI  - Re: short telomere length, cancer survival, and cancer risk in 47 102
      individuals.

PMID- 23868924
TI  - Response.

PMID- 23868922
TI  - H7N9 influenza viruses are transmissible in ferrets by respiratory droplet.
AB  - A newly emerged H7N9 virus has caused 132 human infections with 37 deaths in
      China since 18 February 2013. Control measures in H7N9 virus-positive live
      poultry markets have reduced the number of infections; however, the character of
      the virus, including its pandemic potential, remains largely unknown. We
      systematically analyzed H7N9 viruses isolated from birds and humans. The viruses
      were genetically closely related and bound to human airway receptors; some also
      maintained the ability to bind to avian airway receptors. The viruses isolated
      from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses
      isolated from humans caused up to 30% body weight loss in mice. Most importantly,
      one virus isolated from humans was highly transmissible in ferrets by respiratory
      droplet. Our findings indicate nothing to reduce the concern that these viruses
      can transmit between humans. 

PMID- 23868925
TI  - Has the yearly increase in the renal replacement therapy population ended?
AB  - The recent decline in the number of new patients undergoing dialysis and
      transplantation in the United States may be linked to a reduction in the
      incidence of early-start dialysis, defined as the initiation of renal replacement
      therapy (RRT) at an estimated GFR >=10 ml/min per 1.73 m(2). We examined the most
      recent data from the U.S. Renal Data System to determine how this trend will
      affect the future incidence of ESRD in the United States. The percentage of early
      dialysis starts grew from 19% to 54% of all new starts between 1996 and 2009 but
      remained stable between 2009 and 2011. Similarly, the incident RRT population
      increased substantially in all age groups between 1996 and 2005, with the largest
      increase occurring in patients aged >=75 years. Early dialysis starts accounted
      for most of the increase in the incident RRT population in all age groups during
      this time period, and between 2005 and 2010, the increase slowed dramatically.
      Although the future incident RRT population will be determined in part by
      population growth, these results suggest that later dialysis starts and greater
      use of conservative and palliative care, which may improve quality of life for
      elderly patients with advanced renal failure, will continue to attenuate the
      increase observed in previous years.

PMID- 23868926
TI  - An expanding universe of FSGS genes and phenotypes: LMX1B mutations cause
      familial autosomal dominant FSGS lacking extrarenal manifestations.

PMID- 23868927
TI  - Exposure to intimate partner violence and parental depression increases risk of
      ADHD in preschool children.

PMID- 23868928
TI  - Vulnerability for psychosis at ages 13 and 16 predicts cannabis use at ages 16
      and 19, and cannabis use at age 16 predicts psychosis vulnerability at age 19.

PMID- 23868929
TI  - Increased sacral uptake on a bone scan with SPECT/CT in a patient with
      achondroplasia: normal or abnormal?

PMID- 23868930
TI  - Patient with acute shortness of breath, elevated D-dimer, and a previous history
      of cancer.

PMID- 23868931
TI  - Bronchopleural fistula mimicking chronic obstructive lung disease on 133Xe scan.

PMID- 23868933
TI  - Pharmacological inhibition of phospholipase D protects mice from occlusive
      thrombus formation and ischemic stroke--brief report.
AB  - OBJECTIVE: We recently showed that mice lacking the lipid signaling enzyme
      phospholipase (PL) D1 or both PLD isoforms (PLD1 and PLD2) were protected from
      pathological thrombus formation and ischemic stroke, whereas hemostasis was not
      impaired in these animals. We sought to assess whether pharmacological inhibition
      of PLD activity affects hemostasis, thrombosis, and thrombo-inflammatory brain
      infarction in mice. APPROACH AND RESULTS: Treatment of platelets with the
      reversible, small molecule PLD inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide
      (FIPI), led to a specific blockade of PLD activity that was associated with
      reduced alpha-granule release and integrin activation. Mice that received FIPI at
      a dose of 3 mg/kg displayed reduced occlusive thrombus formation upon chemical
      injury of carotid arteries or mesenterial arterioles. Similarly, FIPI-treated
      mice had smaller infarct sizes and significantly better motor and neurological
      function 24 hours after transient middle cerebral artery occlusion. This
      protective effect was not associated with major intracerebral hemorrhage or
      prolonged tail bleeding times. CONCLUSIONS: These results provide the first
      evidence that pharmacological PLD inhibition might provide a safe therapeutic
      strategy to prevent arterial thrombosis and ischemic stroke.

PMID- 23868932
TI  - Quarterly vs. yearly clinical follow-up of remotely monitored recipients of
      prophylactic implantable cardioverter-defibrillators: results of the REFORM
      trial.
AB  - AIMS: The rapidly increasing number of patients with implantable cardioverter
      defibrillators (ICD) places a large burden on follow-up providers. This study
      investigated the possibility of longer in-office follow-up intervals in primary
      prevention ICD patients under remote monitoring with automatic daily data
      transmissions from the implant memory. METHODS AND RESULTS: Conducted in 155 ICD
      recipients with MADIT II indications, the study compared the burden of scheduled
      and unscheduled ICD follow-up visits, quality of life (SF-36), and clinical
      outcomes in patients randomized to either 3- or 12-month follow-up intervals in
      the period between 3 and 27 months after implantation. Remote monitoring
      (Biotronik Home Monitoring) was used equally in all patients. In contrast to
      previous clinical studies, no calendar-based remote data checks were performed
      between scheduled in-office visits. Compared with the 3-month follow-up interval,
      the 12-month interval resulted in a minor increase in the number of unscheduled
      follow-ups (0.64 vs. 0.27 per patient-year; P = 0.03) and in a major reduction in
      the total number of in-office ICD follow-ups (1.60 vs. 3.85 per patient-year; P <
      0.001). No significant difference was found in mortality, hospitalization rate,
      or hospitalization length during the 2-year observation period, but more patients
      were lost to follow-up in the 12-month group (10 vs. 3; P = 0.04). The SF-36
      scores favoured the 12-month intervals in the domains 'social functioning' and
      'mental health'. CONCLUSION: In prophylactic ICD recipients under automatic daily
      remote monitoring, the extension of the 3-month in-office follow-up interval to
      12 months appeared to safely reduce the ICD follow-up burden during 27 months
      after implantation. CLINICALTRIALSGOV IDENTIFIER: NCT00401466
      (http://www.clinicaltrials.gov/ct2/show/NCT00401466).

PMID- 23868934
TI  - Aortic remodeling after transverse aortic constriction in mice is attenuated with
      AT1 receptor blockade.
AB  - OBJECTIVE: Although hypertension is the most common risk factor for thoracic
      aortic diseases, it is not understood how increased pressures on the ascending
      aorta lead to aortic aneurysms. We investigated the role of angiotensin II type 1
      receptor activation in ascending aortic remodeling in response to increased
      biomechanical forces using a transverse aortic constriction (TAC) mouse model.
      APPROACH AND RESULTS: Two weeks after TAC, the increased biomechanical pressures
      led to ascending aortic dilatation and thickening of the medial and adventitial
      layers of the aorta. There was significant adventitial hyperplasia and
      inflammatory responses in TAC ascending aortas were accompanied by increased
      adventitial collagen, elevated inflammatory and proliferative markers, and
      increased cell density attributable to accumulation of myofibroblasts and
      macrophages. Treatment with losartan significantly blocked TAC-induced vascular
      inflammation and macrophage accumulation. However, losartan only partially
      prevented TAC-induced adventitial hyperplasia, collagen accumulation, and
      ascending aortic dilatation. Increased Tgfb2 expression and phosphorylated-Smad2
      staining in the medial layer of TAC ascending aortas were effectively blocked
      with losartan. In contrast, the increased Tgfb1 expression and adventitial
      phospho-Smad2 staining were only partially attenuated by losartan. In addition,
      losartan significantly blocked extracellular signal-regulated kinase activation
      and reactive oxygen species production in the TAC ascending aorta. CONCLUSIONS:
      Inhibition of the angiotensin II type 1 receptor using losartan significantly
      attenuated the vascular remodeling associated with TAC but did not completely
      block the increased transforming growth factor-beta1 expression, adventitial
      Smad2 signaling, and collagen accumulation. These results help to delineate the
      aortic transforming growth factor-beta signaling that is dependent and
      independent of the angiotensin II type 1 receptor after TAC.

PMID- 23868935
TI  - LRP1 protects the vasculature by regulating levels of connective tissue growth
      factor and HtrA1.
AB  - OBJECTIVE: Low-density lipoprotein receptor-related protein 1 (LRP1) is a large
      endocytic and signaling receptor that is abundant in vascular smooth muscle
      cells. Mice in which the lrp1 gene is deleted in smooth muscle cells (smLRP1(-/
      )) on a low-density lipoprotein receptor-deficient background display excessive
      platelet derived growth factor-signaling, smooth muscle cell proliferation,
      aneurysm formation, and increased susceptibility to atherosclerosis. The
      objectives of the current study were to examine the potential of LRP1 to modulate
      vascular physiology under nonatherogenic conditions. APPROACH AND RESULTS: We
      found smLRP1(-/-) mice to have extensive in vivo aortic dilatation accompanied by
      disorganized and degraded elastic lamina along with medial thickening of the
      arterial vessels resulting from excess matrix deposition. Surprisingly, this was
      not attributable to excessive platelet derived growth factor-signaling. Rather,
      quantitative differential proteomic analysis revealed that smLRP1(-/-) vessels
      contain a 4-fold increase in protein levels of high-temperature requirement
      factor A1 (HtrA1), which is a secreted serine protease that is known to degrade
      matrix components and to impair elastogenesis, resulting in fragmentation of
      elastic fibers. Importantly, our study discovered that HtrA1 is a novel LRP1
      ligand. Proteomics analysis also identified excessive accumulation of connective
      tissue growth factor, an LRP1 ligand and a key mediator of fibrosis. CONCLUSIONS:
      Our findings suggest a critical role for LRP1 in maintaining the integrity of
      vessels by regulating protease activity as well as matrix deposition by
      modulating HtrA1 and connective tissue growth factor protein levels. This study
      highlights 2 new molecules, connective tissue growth factor and HtrA1, which
      contribute to detrimental changes in the vasculature and, therefore, represent
      new target molecules for potential therapeutic intervention to maintain vessel
      wall homeostasis.

PMID- 23868936
TI  - Induction of ATF3 gene network by triglyceride-rich lipoprotein lipolysis
      products increases vascular apoptosis and inflammation.
AB  - OBJECTIVE: Elevation of triglyceride-rich lipoproteins (TGRLs) contributes to the
      risk of atherosclerotic cardiovascular disease. Our work has shown that TGRL
      lipolysis products in high physiological to pathophysiological concentrations
      cause endothelial cell injury; however, the mechanisms remain to be delineated.
      APPROACH AND RESULTS: We analyzed the transcriptional signaling networks in
      arterial endothelial cells exposed to TGRL lipolysis products. When human aortic
      endothelial cells in culture were exposed to TGRL lipolysis products, activating
      transcription factor 3 (ATF3) was identified as a principal response gene.
      Induction of ATF3 mRNA and protein was confirmed by quantitative reverse
      transcription polymerase chain reaction and Western blot respectively.
      Immunofluorescence analysis showed that ATF3 accumulated in the nuclei of cells
      treated with lipolysis products. Nuclear expression of phosphorylated c-Jun N
      terminal kinase (JNK), previously shown to be an initiator of the ATF3 signaling
      cascade, also was demonstrated. Small interfering RNA (siRNA)-mediated inhibition
      of ATF3 blocked lipolysis products-induced transcription of E-selectin and
      interleukin-8, but not interleukin-6 or nuclear factor-kappaB. c-Jun, a
      downstream protein in the JNK pathway, was phosphorylated, whereas expression of
      nuclear factor-kappaB-dependent JunB was downregulated. Additionally, JNK siRNA
      suppressed ATF3 and p-c-Jun protein expression, suggesting that JNK is upstream
      of the ATF3 signaling pathway. In vivo studies demonstrated that infusion of TGRL
      lipolysis products into wild-type mice induced nuclear ATF3 accumulation in
      carotid artery endothelium. ATF3(-/-) mice were resistant to vascular apoptosis
      precipitated by treatment with TGRL lipolysis products. Also peripheral blood
      monocytes isolated from postprandial humans had increased ATF3 expression as
      compared with fasting monocytes. CONCLUSIONS: This study demonstrates that TGRL
      lipolysis products activate ATF3-JNK transcription factor networks and induce
      endothelial cells inflammatory response.

PMID- 23868937
TI  - Insulin resistance is associated with significant clinical atherosclerosis in
      nondiabetic patients with acute myocardial infarction.
AB  - OBJECTIVE: The prevalence of insulin resistance (IR) is increasing worldwide
      because of increasing age, obesity, and physical inactivity. Emerging evidence
      supports a direct proatherogenic effect of IR on the coronary vasculature, but
      the relation between IR and angiographic atherosclerosis in a real-world clinical
      setting is uncertain. In this work, we assessed whether IR is independently
      associated with clinically significant angiographic atherosclerosis in
      nondiabetic individuals. APPROACH AND RESULTS: We examined the association
      between IR and the extent of coronary atherosclerosis determined by angiography
      in 1073 nondiabetic patients surviving acute myocardial infarction. Patients were
      divided into quartiles on the basis of the homeostasis model assessment grading
      of IR, and associations between IR and multivessel coronary artery disease,
      defined as >= 2 arteries with >= 70% stenosis (or >= 50% left main stenosis),
      were analyzed in bivariate and multivariable modeling. Overall, the cohort had a
      median age of 56 years; 28.9% women and 21.8% nonwhite. The crude prevalence of
      multivessel coronary artery disease was 37.8%, 42.3%, 47.2%, and 48.0% for
      homeostasis model assessment grading of IR quartiles 1, 2, 3, and 4, respectively
      (P(trend) = 0.009). In multivariable modeling, compared with quartile 1, both
      quartile 3 (relative risk [95% confidence interval], 1.31 [1.07-1.60]) and
      quartile 4 (1.29 [1.03-1.60]) were independently associated with multivessel
      coronary artery disease. Covariates in the model included patient demographic and
      clinical characteristics and metabolic factors (low-density lipoprotein
      cholesterol, high-density lipoprotein-cholesterol, triglyceride, glycosylated
      hemoglobin, and high-sensitivity C-reactive protein). CONCLUSIONS: We demonstrate
      an independent association between IR and multivessel coronary artery disease in
      nondiabetic postmyocardial infarction patients. Our findings strengthen the
      experimental evidence for a direct atherogenic effect of IR independent of
      glucose control and other components of the metabolic syndrome.

PMID- 23868938
TI  - Toll-like receptor 2/6 agonist macrophage-activating lipopeptide-2 promotes
      reendothelialization and inhibits neointima formation after vascular injury.
AB  - OBJECTIVE: Reendothelialization after vascular injury (ie, balloon angioplasty or
      stent implantation) is clinically extremely relevant to promote vascular healing.
      We here investigated the therapeutic potential of the toll-like receptor 2/6
      agonist macrophage-activating lipopeptide (MALP)-2 on reendothelialization and
      neointima formation in a murine model of vascular injury. APPROACH AND RESULTS:
      The left common carotid artery was electrically injured, and reendothelialization
      was quantified by Evans blue staining after 3 days. A single injection of MALP-2
      (1 or 10 ug, IV) after vascular injury accelerated reendothelialization
      (P<0.001). Proliferation of endothelial cells at the wound margins determined by
      5-ethynyl-2'-deoxyuridine incorporation was significantly higher in MALP-2
      treated animals (P<0.05). Furthermore, wire injury-induced neointima formation of
      the left common carotid artery was completely prevented by a single injection of
      MALP-2 (10 ug, IV). In vitro, MALP-2 induced proliferation (BrdU incorporation)
      and closure of an artificial wound of endothelial cells (P<0.05) but not of
      smooth muscle cells. Protein array and ELISA analysis of isolated primary
      endothelial cells and ex vivo stimulated carotid segments revealed that MALP-2
      stimulated the release of multiple growth factors and cytokines predominantly
      from endothelial cells. MALP-2 induced a strong activation of the mitogen
      activated protein kinase cascade in endothelial cells, which was attenuated in
      smooth muscle cells. Furthermore, MALP-2 significantly enhanced circulating
      monocytes and hematopoietic progenitor cells. CONCLUSIONS: The toll-like receptor
      2/6 agonist MALP-2 promotes reendothelialization and inhibits neointima formation
      after experimental vascular injury via enhanced proliferation and migration of
      endothelial cells. Thus, MALP-2 represents a novel therapeutic option to
      accelerate reendothelialization after vascular injury.

PMID- 23868939
TI  - Novel formulation of a reconstituted high-density lipoprotein (CSL112)
      dramatically enhances ABCA1-dependent cholesterol efflux.
AB  - OBJECTIVE: The ability of high-density lipoprotein (HDL) to remove cholesterol
      from atherosclerotic plaque is thought to underlie its inverse correlation with
      cardiovascular risk. Our objective was to produce and characterize a human
      apolipoprotein AI (apoA-I) product optimized to treat clinical atherosclerotic
      disease. APPROACH AND RESULTS: A new formulation of full length, plasma-derived
      human apoA-I termed CSL112 was designed to maximize the cholesterol efflux from
      cells and exhibit favorable pharmacological properties. CSL112 is a disc-shaped
      particle that strongly elevates cholesterol esterification and shows good
      pharmacokinetics in rabbits. Infusion of CSL112 into rabbits caused a strong and
      immediate increase in the ATP binding cassette transporter A1 (ABCA1)-dependent
      efflux capacity of plasma, an increase in plasma unesterified cholesterol and
      rapid subsequent cholesterol esterification. In the presence of human plasma,
      CSL112 was significantly more potent than native HDL at enhancing cholesterol
      efflux from macrophages, and the efflux elevation was predominantly via the ABCA1
      transporter. Consistent with this observation, addition of CSL112 to plasma led
      to generation of high levels of HDL-VS, a favorable substrate for ABCA1. The
      lipid profile of plasma did not affect these behaviors. In studies with whole
      human blood, CSL112 reduced expression of intercellular adhesion molecule 1 and
      cytokine secretion, and as with cholesterol efflux, these activities were
      substantially greater than those of native HDL assayed in parallel. CONCLUSIONS:
      CSL112 has favorable pharmacological properties and strongly elevates the ability
      of plasma to withdraw cholesterol from cells. Preferential elevation of ABCA1
      dependent efflux may target atherosclerotic plaque for cholesterol removal and
      this property makes CSL112 a promising candidate therapy for acute coronary
      syndrome.

PMID- 23868940
TI  - NOD2-mediated innate immune signaling regulates the eicosanoids in
      atherosclerosis.
AB  - OBJECTIVE: The activity of eicosanoid pathways is critical to the inflammatory
      and immune responses that are associated with the progression of atherosclerosis.
      Yet, the signals that regulate these pathways are poorly understood. Here, we
      address whether the innate immune signals of nucleotide-binding oligomerization
      domain-containing protein (NOD) 2 affect eicosanoids metabolism in
      atherosclerosis. APPROACH AND RESULTS: Analysis of human carotid plaques revealed
      that NOD2 was abundantly expressed at both mRNA and protein levels by endothelial
      cells and macrophages. Stimulation of NOD2 in ex vivo-cultured carotid plaques by
      muramyl dipeptide, an extrinsic ligand of NOD2, led to release of prostaglandin
      E2, upregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1,
      and to downregulation of cyclooxygenase-1. NOD2 was coexpressed with
      cyclooxygenase-2 in lesional macrophages. NOD2-induced cyclooxygenase-2
      expression in macrophages was dependent on p38 mitogen-activated protein kinase
      activation and was mediated by interleukin-1beta and tumor necrosis factor-alpha.
      Selective lipidomic analysis of the eicosanoids released by the carotid plaques
      characterized the metabolites of 12-, 5-, and 15-lipoxygenase as the predominant
      eicosanoids that were produced by the atherosclerotic lesion in the absence of
      additional stimuli. Unlike the prostaglandin E2 pathway, metabolic activity of
      the lipoxygenase pathways was not altered on the short-term activation of NOD2 in
      carotid plaques. CONCLUSIONS: These results suggest that atherosclerosis may
      involve enhanced NOD2-mediated innate immunity. Activation of NOD2 preferentially
      upregulates the prostaglandin E2 pathway. Nevertheless, lipoxygenase pathways,
      such as 12-lipoxygenase, predominate the basal synthesis and metabolism of
      eicosanoids in atherosclerotic plaques. These findings provide new insights into
      the regulation of eicosanoids in atherosclerosis.

PMID- 23868941
TI  - Therapeutic reendothelialization by induced pluripotent stem cells after vascular
      injury--brief report.
AB  - OBJECTIVE: Endothelial damage is an early requisite step for atherosclerosis
      after vascular injury. It has been reported that vascular wall cells can develop
      from induced pluripotent stem (iPS) cell-derived fetal liver kinase-1-positive
      (Flk-1(+)) cells. Here, we investigated the efficacies of intravenously
      administered iPS cell-derived Flk-1(+) cells on reendothelialization and
      neointimal hyperplasia in a mouse model of vascular injury. APPROACH AND RESULTS:
      Femoral arteries of KSN nude mice were injured using a steel wire. Mouse iPS cell
      derived Flk-1(+) or Flk-1(-) cells were intravenously injected into those mice at
      24 hours after vascular injury. Delivery of iPS cell-derived Flk-1(+) cells
      significantly attenuated neointimal hyperplasia compared with controls. Evans
      blue staining of the injured vessel revealed that administration of iPS cell
      derived Flk-1(+) significantly enhanced reendothelialization compared with the
      Flk-1(-) cell control group. Recruitment of PKH26-labeled iPS cell-derived Flk
      1(+) cells to the site of injury was also detectable. Expression level of CXCR4
      in iPS cell-derived Flk-1(+) cells was 7.5-fold higher than that of iPS cell
      derived Flk-1(-) cells. Stromal cell-derived factor-1alpha treatment
      significantly enhanced adhesion and migration of iPS cell-derived Flk-1(+) cells
      to the endothelia, but these were not observed in Flk-1(-) cells. CONCLUSIONS:
      Intravenously administered iPS cell-derived Flk-1(+) cells are recruited to the
      site of vascular injury, thereby enhancing reendothelialization followed by
      suppression of neointimal hyperplasia. Administration of iPS cell-derived Flk
      1(+) cells is a potentially useful therapeutic means for vascular dysfunction and
      prevention of restenosis after angioplasty.

PMID- 23868942
TI  - Rictor in perivascular adipose tissue controls vascular function by regulating
      inflammatory molecule expression.
AB  - OBJECTIVE: Perivascular adipose tissue (PVAT) wraps blood vessels and modulates
      vasoreactivity by secretion of vasoactive molecules. Mammalian target of
      rapamycin complex 2 (mTORC2) has been shown to control inflammation and is
      expressed in adipose tissue. In this study, we investigated whether adipose
      specific deletion of rictor and thereby inactivation of mTORC2 in PVAT may
      modulate vascular function by increasing inflammation in PVAT. APPROACH AND
      RESULTS: Rictor, an essential mTORC2 component, was deleted specifically in mouse
      adipose tissue (rictor(ad-/-)). Phosphorylation of mTORC2 downstream target Akt
      at Serine 473 was reduced in PVAT from rictor(ad-/-) mice but unaffected in
      aortic tissue. Ex vivo functional analysis of thoracic aortae revealed increased
      contractions and impaired dilation in rings with PVAT from rictor(ad-/-) mice.
      Adipose rictor knockout increased gene expression and protein release of
      interleukin-6, macrophage inflammatory protein-1alpha, and tumor necrosis factor
      alpha in PVAT as shown by quantitative real-time polymerase chain reaction and
      Bioplex analysis for the cytokines in the conditioned media, respectively.
      Moreover, gene and protein expression of inducible nitric oxide synthase was
      upregulated without affecting macrophage infiltration in PVAT from rictor(ad-/-)
      mice. Inhibition of inducible nitric oxide synthase normalized vascular
      reactivity in aortic rings from rictor(ad-/-) mice with no effect in
      rictor(fl/fl) mice. Interestingly, in perivascular and epididymal adipose depots,
      high-fat diet feeding induced downregulation of rictor gene expression.
      CONCLUSIONS: Here, we identify mTORC2 as a critical regulator of PVAT-directed
      protection of normal vascular tone. Modulation of mTORC2 activity in adipose
      tissue may be a potential therapeutic approach for inflammation-related vascular
      damage.

PMID- 23868944
TI  - Cardioprotective effects of exenatide in patients with ST-segment-elevation
      myocardial infarction undergoing primary percutaneous coronary intervention:
      results of exenatide myocardial protection in revascularization study.
AB  - OBJECTIVE: Experimental evidence suggests that exenatide, a glucagon-like peptide
      1 receptor analogue, has significant cardiovascular protective effects in various
      conditions. We examined whether routine use of exenatide at the time of primary
      percutaneous coronary intervention would reduce infarct size in patients with ST
      segment-elevation myocardial infarction. APPROACH AND RESULTS: Fifty-eight
      patients with ST-segment-elevation myocardial infarction and thrombolysis in
      myocardial infarction flow 0 were enrolled in the study and randomly assigned to
      receive either exenatide or placebo (saline) subcutaneously. Infarct size was
      assessed by measuring the release of creatine kinase-MB and troponin I during 72
      hours and by performing cardiac magnetic resonance imaging at 1 month after
      infarction. Routine and speckle tracking echocardiography was performed at
      initial presentation and at 3 days and 6 months after primary percutaneous
      coronary intervention. The exenatide and control groups had similar results with
      respect to ischemia time, demographic characteristics, and ejection fraction
      before primary percutaneous coronary intervention. The releases of creatine
      kinase-MB and troponin I were significantly reduced in the exenatide group. In 58
      patients evaluated with cardiac magnetic resonance, the absolute mass of delayed
      hyperenhancement was significantly reduced in the exenatide group as compared
      with the control group (12.8+/-11.7 versus 26.4+/-11.6 g; P<0.01). At 6 months,
      the exenatide group showed a significantly lower value of E/E' with improved
      strain parameters. No significant adverse effects of exenatide administration
      were detected. CONCLUSIONS: In patients with ST-segment-elevation myocardial
      infarction, adjunctive exenatide therapy with primary percutaneous coronary
      intervention was associated with reduction of infarct size and improvement of
      subclinical left ventricular function.

PMID- 23868945
TI  - The natural history of cerebrovascular disease: a closer look at paraclinoid
      aneurysms and epileptogenic AVMs.

PMID- 23868946
TI  - A roadmap for genetic testing in ALS.

PMID- 23868943
TI  - Compartmentalized protective and detrimental effects of endogenous macrophage
      migration-inhibitory factor mediated by CXCR2 in a mouse model of myocardial
      ischemia/reperfusion.
AB  - OBJECTIVE: Here, we aimed to clarify the role of CXC chemokine receptor (CXCR) 2
      in macrophage migration-inhibitory factor (MIF)-mediated effects after myocardial
      ischemia and reperfusion. As a pleiotropic chemokine-like cytokine, MIF has been
      identified to activate multiple receptors, including CD74 and CXCR2. In models of
      myocardial infarction, MIF exerts both proinflammatory effects and protective
      effects in cardiomyocytes. Similarly, CXCR2 displays opposing effects in resident
      versus circulating cells. APPROACH AND RESULTS: Using bone marrow
      transplantation, we generated chimeric mice with Cxcr2(-/-) bone marrow-derived
      inflammatory cells and wild-type (wt) resident cells (wt/Cxcr2(-/-)), Cxcr2(-/-)
      cardiomyocytes and wt bone marrow-derived cells (Cxcr2(-/-)/wt), and wt controls
      reconstituted with wt bone marrow (wt/wt). All groups were treated with anti-MIF
      or isotype control antibody before they underwent myocardial ischemia and
      reperfusion. Blocking MIF increased infarction size and impaired cardiac function
      in wt/wt and wt/CXCR2(-/-) mice but ameliorated functional parameters in Cxcr2(-/
      )/wt mice, as analyzed by echocardiography and Langendorff perfusion. Neutrophil
      infiltration and angiogenesis were unaltered by MIF blockade or Cxcr2 deficiency.
      Monocyte infiltration was blunted in wt/Cxcr2(-/-) mice and reduced by MIF
      blockade in wt/wt and Cxcr2(-/-)/wt mice. Furthermore, MIF blockade attenuated
      collagen content in all groups in a CXCR2-independent manner. CONCLUSIONS: The
      compartmentalized and opposing effects of MIF after myocardial ischemia and
      reperfusion are largely mediated by CXCR2. Although MIF confers protective
      effects by improving myocardial healing and function through CXCR2 in resident
      cells, thereby complementing paracrine effects through CD74/AMP-activated protein
      kinase, it exerts detrimental effects on CXCR2-bearing inflammatory cells by
      increasing monocyte infiltration and impairing heart function. These dichotomous
      findings should be considered when developing novel therapeutic strategies to
      treat myocardial infarction.

PMID- 23868947
TI  - Neurogenic paradoxical breathing.

PMID- 23868948
TI  - Should all patients with ALS have genetic testing?

PMID- 23868949
TI  - Novel modulating effects of PKC family genes on the relationship between serum
      vitamin D and relapse in multiple sclerosis.
AB  - BACKGROUND: The interplay between genes and environmental factors on multiple
      sclerosis (MS) clinical course has been little studied. METHODS: We conducted a
      prospective cohort study of 141 participants with relapsing-remitting MS (RRMS)
      and genotype data followed from 2002 to 2005 and examined genes in the vitamin D
      metabolism and vitamin D receptor (VDR)/retinoid X receptor (RXR) transcription
      factor formation pathway. Gene-vitamin D interactions and the genetic predictors
      of relapse were assessed using survival analysis. Genetic predictors of 25
      hydroxyvitamin D (25(OH)D) were evaluated by multilevel mixed-effects linear
      regression. Significance threshold was adjusted by Bonferroni correction for the
      number of genes evaluated. RESULTS: The relationship between 25(OH)D and hazard
      of relapse was significantly different for different alleles of two intronic
      single nucleotide polymorphisms (SNPs) (rs908742 in PRKCZ and rs3783785 in PRKCH)
      in the protein kinase C (PKC) family genes (p(interaction)=0.001, p(adj)=0.021,
      respectively). Two other intronic SNPs (rs1993116 in CYP2R1and rs7404928 in
      PRKCB) were significantly associated with lower levels of 25(OH)D
      (p(interaction)=0.001, p(adj)=0.021, respectively). A cumulative effect of
      multiple 'risk' genotypes on 25(OH)D levels and hazard of relapse was observed
      for the significant SNPs (p(trend)=7.12*10(-6) for 25(OH)D levels,
      p(trend)=8.86*10(-6) for hazard of relapse). CONCLUSIONS: Our data support the
      hypothesis that gene-vitamin D interactions may influence MS clinical course and
      that the PKC family genes may play a role in the pathogenesis of MS relapse
      through modulating the association between 25(OH)D and relapse.

PMID- 23868950
TI  - Stereotactic lesioning in focal epilepsy or less is more--but why has it not
      worked in the past?

PMID- 23868951
TI  - Clinical predictor of pre- or minimally invasive pulmonary adenocarcinoma:
      possibility of sub-classification of clinical T1a.
AB  - OBJECTIVES: A new pathological classification for pre- and minimally invasive
      adenocarcinoma has been established, with distinction prior to surgery crucial
      because of the extremely good prognosis. METHODS: Of 412 patients who underwent
      surgery for lung cancer from 2008 to 2011, 110 classified as c-stage I had each
      of the following four parameters assessed for predictive power for pre- or
      minimally invasive adenocarcinoma and relapse-free survival (RFS): (i) whole
      tumour size (WS) shown by computed tomography (CT) , (ii) size of the solid (SS)
      component in CT findings, (iii) maximum standard uptake value in
      fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan images (SUVmax)
      and (iv) serum level of carcinoembryonic antigen. RESULTS: For prediction of pre-
      or minimally invasive adenocarcinoma, the area under the receiver-operating curve
      was >0.7 for all the four parameters, while only SS was found to be an
      independent factor in multivariate logistic regression analysis. In Cox
      proportional hazard model analysis, SS and SUVmax were statistically significant,
      and SS was exclusively independent in multivariate analysis. Differences in RFS
      between T1a and T1b were more pronounced when using SS compared with WS. In the
      sub-classification of T1a, we used a breakpoint of 1.0 cm in SS (T1a-alpha and
      T1a-beta), which resulted in a 2-year RFS rate of 1.00 for T1a-alpha (n=21), 0.89
      for T1a-beta (n=27) and 0.68 for T1b (n=26) (P=0.002 between T1a-beta and T1b).
      CONCLUSIONS: The SS parameter was useful to distinguish pre- and minimally
      invasive adenocarcinoma from other types of lung cancer, and set a T1a sub
      classification.

PMID- 23868952
TI  - Onion skin technique for open surgical replacement of aortic arch following
      primary endoprothesic thoracic aorta treatment.
AB  - Endovascular aortic replacement (EVAR) techniques have become the first choice
      option for many aortic diseases in patients in whom standard open surgery was
      contraindicated or with high surgical risk. A secondary open surgical treatment,
      following a primary EVAR procedure, could, however, be challenging depending on
      the type, the extension and the position of primary endoprosthesis. Here, we
      describe an original and easy technique capable of simplifying a secondary aortic
      arch replacement following EVAR treatment of the descending thoracic aorta. The
      basic concept of such techniques is similar to that of the conventional 'elephant
      trunk' technique and is based on an inverted straight tube graft inserted into
      the endoprosthesis and anastomized using a multi-layer double suture with
      external strip felt of Dacron. 

PMID- 23868953
TI  - Innominate artery compression of the trachea in patients with neurological or
      neuromuscular disorders.
AB  - OBJECTIVES: The purpose of this study was to review and assess our surgical
      management of innominate artery compression of the trachea (IACT) in patients
      with neurological or neuromuscular disorders (NMDs). METHODS: Thirty patients
      with NMD who underwent surgical treatment for IACT at Kobe Children's Hospital
      and Kobe University Hospital from 2002 to 2012, were enrolled in this
      retrospective study. The clinical outcomes of preventive elective surgery for
      IACT (Group A, n=20) were assessed and compared with those of emergent surgery
      (Group B, n=10). RESULTS: A total of 27 patients underwent innominate artery
      transection (17 in Group A and 10 in Group B), and 3 patients in Group A
      underwent innominate artery reimplantation using prosthetic graft interposition.
      No operative or early death occurred. There were no cases of postoperative
      mediastinitis or neurological complications. The operative benefits in Group A
      included a smaller skin incision, more limited sternotomy, less blood loss,
      shorter operative time and shorter hospital stay, compared with Group B. No blood
      transfusion was required in Group A. The number of patients in whom cerebral
      circulation was assessed before surgery in Group A was significantly higher than
      those in Group B. CONCLUSIONS: Preventive elective surgery for IACT provides many
      advantages, including minimally invasive procedures and successful postoperative
      outcomes without neurological complications in patients with NMD. Because this
      surgical management can prevent the tragic occurrence of a tracheo-innominate
      artery fistula or an exacerbation of tracheomalacia, it would be an optimal
      surgical treatment for IACT to improve the quality of life in patients with NMD.

PMID- 23868954
TI  - Management of Boerhaave's syndrome with an over-the-scope clip.
AB  - Boerhaave's syndrome is a spontaneous barotraumatic disruption of the distal
      oesophagus secondary to an abrupt increase in intraoesophageal pressure during
      vomiting. Management ranges from a conservative approach to an oesophagectomy.
      The over-the-scope-clip (OTSC, Ovesco Endoscopy GmbH, Tuebingen, Germany) system
      is a newly designed clipping method for tissue mechanical compression in the
      gastrointestinal tract. We report the case of a patient referred with a delayed
      diagnosis of Boerhaave's syndrome and successfully treated by OTSC application
      followed by lung decortication. 

PMID- 23868955
TI  - Single-centre experience of 85 patients with a continuous-flow left ventricular
      assist device: clinical practice and outcome after extended support.
AB  - OBJECTIVES: We evaluated our single-centre clinical experience with the HeartMate
      II (HM II) left ventricular assist device (LVAD) as a bridge to transplantation
      (BTT) in end-stage heart failure (HF) patients. METHODS: Survival rates,
      echocardiographic parameters, laboratory values and adverse events of 85
      consecutive patients supported with a HM II were evaluated. RESULTS: Overall,
      mean age was 45 +/- 13 years, 62 (73%) were male and non-ischaemic dilatated
      cardiomyopathy was present in 60 (71%) patients. The median duration of
      mechanical support was 387 days (IQR 150-600), with a range of 1-1835 days. The 6
      month, 1-, 2-, 3- and 4-year survival rates during HM II LVAD support were 85,
      81, 76, 76 and 68%, respectively. Echocardiographic parameters demonstrated
      effective left ventricular unloading, while laboratory results reflected adequate
      organ perfusion. However, HM II support was associated with adverse events, such
      as infections in 42 patients (49%; 0.67 events/patient-year), cardiac arrhythmia
      in 44 (52%; 0.86 events/patient-year), bleeding complications in 32 (38%; 0.43
      events/patient-year) and neurological dysfunction in 17 (20%; 0.19 events/patient
      year). CONCLUSIONS: In view of the increasing shortage of donor hearts, HM II
      LVAD support may be considered a life-saving treatment in end-stage HF patients,
      with good survival. However, it is still associated with some serious adverse
      events, of which neurological complications are the most critical.

PMID- 23868956
TI  - SAPA tool: finding protein regions by combination of amino acid composition,
      scaled profiles, patterns and rules.
AB  - SUMMARY: Functional modules within protein sequences are often extracted by
      consensus sequence patterns representing a linear motif; however, other
      functional regions may only be described by combined features such as amino acid
      composition, profiles of amino acid properties and randomly distributed short
      sequence motifs. If only a small number of functional examples are well
      characterized, the researcher needs a tool to extract similar sequences for
      further investigation. AVAILABILITY AND IMPLEMENTATION: We provide the web
      application 'SAPA tool', which allows the user to search with combined
      properties, ranks the extracted target regions by an integrated score, estimates
      false discovery rates by using decoy sequences and provides them as a sequence
      file or spreadsheet. Source code, user manual and the web application implemented
      in Perl, HTML, CSS and JavaScript and running on Apache are freely available at
      http://sapa-tool.uio.no/sapa/

PMID- 23868957
TI  - Tiki, at the head of a new superfamily of enzymes.
AB  - Tiki proteins appear to antagonize Wnt signalling pathway by acting as Wnt
      proteases, thereby affecting Wnt solubility by its amino-terminal cleavage. Tiki1
      protease activity was shown to be metal ion-dependent and was inhibited by
      chelating agents and thus was tentatively proposed to be a metalloprotease.
      Nevertheless, Tiki proteins exhibit no detectable sequence similarity to
      previously described metalloproteases, but instead have been reported as being
      homologues of TraB proteins (Pfam ID: PF01963), a widely distributed family of
      unknown function and structure. Here, we show that Tiki proteins are members of a
      new superfamily of domains contained not just in TraB proteins, but also in
      erythromycin esterase (Pfam ID: PF05139), DUF399 (domain of unknown function 399;
      Pfam ID: PF04187) and MARTX toxins that contribute to host invasion and
      pathogenesis by bacteria. We establish the core fold of this enzymatic domain and
      its catalytic residues.

PMID- 23868958
TI  - Measurement of human brown adipose tissue volume and activity using anatomic MR
      imaging and functional MR imaging.
AB  - The aim of this study was to assess the volume and function of human brown
      adipose tissue (BAT) in vivo using MR imaging. METHODS: BAT volumes under
      thermoneutral conditions in the cervical areas were assessed via water-fat
      contrast using the Dixon method and via water-saturation efficiency using fast
      spin-echo and T2-weighted images. The existence of cervical BAT was also assessed
      by (18)F-FDG PET/CT scans in the same subjects. BAT functionality was assessed
      via functional MR imaging (fMRI) blood oxygenation level-dependent (BOLD) signal
      changes in response to a mild cold challenge. RESULTS: Under thermoneutral
      conditions, we were able to distinguish BAT from white adipose tissue in the
      cervical and supraclavicular fat. BAT showed higher water-to-fat contrast and
      higher water-saturation efficiency in MR imaging scans. The location and volume
      of BAT assessed by MR imaging were comparable to the measurements by (18)F-FDG
      PET/CT scans. During mild cold challenge, BOLD fMRI signal increased in BAT by
      10.7% +/- 1.8% (P < 0.01). CONCLUSION: We demonstrated the feasibility of using
      MR imaging and fMRI to assess BAT volume and BAT responses to mild cold
      stimulation in the cervical areas of human subjects.

PMID- 23868959
TI  - Macular displacement following rhegmatogenous retinal detachment repair.
AB  - AIMS: To investigate the incidence of macula displacement and symptoms of
      distortion following rhegmatogenous retinal detachment (RRD) repair, quantify the
      displacement where seen and further characterise the nature of the displacement.
      METHODS: Consecutive patients undergoing primary RRD repair were assessed
      postoperatively with fundus autofluorescence and optical coherence tomography
      imaging, and the extent of macula displacement quantified using a novel means.
      Findings were examined for correlations with symptoms and pre-operative features.
      RESULTS: Macula displacement was evident postoperatively in 72% of 32 consecutive
      fovea-involving detachments treated with vitrectomy and gas. It was also evident
      in 5/17 foveal-sparing cases treated with vitrectomy and gas and in two of two
      patients with fovea-involving detachments treated with vitrectomy and oil. There
      was a significant correlation between the presence of macula displacement and
      symptoms of distortion in the early postoperative period (p=0.013). Symptomatic
      patients described bending of lines with or without objects appearing smaller or
      narrower in the operated eye. Quantifying the displacement demonstrated that the
      extent of displacement was associated with distance from the optic disc (p=0.005)
      and the extent of retinal detachment. CONCLUSIONS: Displacement of the macula is
      common following RRD repair and heterogeneous in nature. Most affected patients
      are symptomatic in the early postoperative period.

PMID- 23868960
TI  - eComment. Does pectus tunneloscopy make the Nuss repair for pectus excavatum
      safe?

PMID- 23868961
TI  - eComment. Paradigm shift in surgery for massive pulmonary embolism: if not now
      then when?

PMID- 23868962
TI  - eComment. Management of percutaneous coronary intervention complications.

PMID- 23868963
TI  - eComment. Should we operate on nonagenarians in the transcatheter aortic valve
      implantation era?

PMID- 23868964
TI  - eComment. Pleiotropic effects of statins after cardiac surgery.

PMID- 23868965
TI  - eComment. Prediction score for cerebrovascular events after coronary artery
      bypass grafting.

PMID- 23868966
TI  - eComment. Prevention of sternal wound infection.

PMID- 23868967
TI  - eComment. Role of global longitudinal strain for evaluation of asymptomatic
      severe aortic stenosis.

PMID- 23868968
TI  - eComment. Balancing the pulmonary circulation in tricuspid atresia with an
      aortopulmonary window.

PMID- 23868969
TI  - eReply. Re: Balancing the pulmonary circulation in tricuspid atresia with an
      aortopulmonary window.

PMID- 23868970
TI  - eComment. Rare combination of aortic anomalies.

PMID- 23868971
TI  - Optimal control of disease infestations on a lattice.
AB  - The design of durable and sustainable strategies for the control of plant
      diseases is not possible without due consideration of landscape structure and
      economic factors. However, many studies on control strategies of plant
      infestation have overlooked these considerations. In this paper, we address the
      problem of how best to deploy resources for the control of disease outbreaks
      during a single agricultural season. We consider a spatial model for the spread
      of a plant pathogen over an agricultural region, and model the effect of control
      on disease dynamics. We associate with a control strategy a 'costs function' that
      balances amount invested for treatment to the cost incurred by disease
      infestation. Our objective is to minimize the level of disease infestation and
      the effort of control. We prove the existence of a solution to the optimal
      control problem, and devise a numerical algorithm to compute it. We present
      results of our numerical studies, and show that the solution depends on the
      interplay between economic and epidemiological factors, as well as the nature of
      the control agent. 

PMID- 23868973
TI  - Mapping CRMP3 domains involved in dendrite morphogenesis and voltage-gated
      calcium channel regulation.
AB  - Although hippocampal neurons are well-distinguished by the morphological
      characteristics of their dendrites and their structural plasticity, the
      mechanisms involved in regulating their neurite initiation, dendrite growth,
      network formation and remodeling are still largely unknown, in part because the
      key molecules involved remain elusive. Identifying new dendrite-active cues could
      uncover unknown molecular mechanisms that would add significant understanding to
      the field and possibly lead to the development of novel neuroprotective therapy
      because these neurons are impaired in many neuropsychiatric disorders. In our
      previous studies, we deleted the gene encoding CRMP3 in mice and identified the
      protein as a new endogenous signaling molecule that shapes diverse features of
      the hippocampal pyramidal dendrites without affecting axon morphology. We also
      found that CRMP3 protects dendrites against dystrophy induced by prion peptide
      PrP(106-126). Here, we report that CRMP3 has a profound influence on neurite
      initiation and dendrite growth of hippocampal neurons in vitro. Our deletional
      mapping revealed that the C-terminus of CRMP3 probably harbors its dendritogenic
      capacity and supports an active transport mechanism. By contrast, overexpression
      of the C-terminal truncated CRMP3 phenocopied the effect of CRMP3 gene deletion
      with inhibition of neurite initiation or decrease in dendrite complexity,
      depending on the stage of cell development. In addition, this mutant inhibited
      the activity of CRMP3, in a similar manner to siRNA. Voltage-gated calcium
      channel inhibitors prevented CRMP3-induced dendritic growth and somatic Ca(2+)
      influx in CRMP3-overexpressing neurons was augmented largely via L-type channels.
      These results support a link between CRMP3-mediated Ca(2+) influx and CRMP3
      mediated dendritic growth in hippocampal neurons.

PMID- 23868972
TI  - PDZ-RhoGEF is essential for CXCR4-driven breast tumor cell motility through
      spatial regulation of RhoA.
AB  - The CXCL12-CXCR4 chemokine signaling pathway is a well-established driver of
      cancer progression. One key process promoted by CXCR4 stimulation is tumor cell
      motility; however, the specific signaling pathways leading to migration remain
      poorly understood. Previously, we have shown that CXCL12 stimulation of migration
      depends on temporal regulation of RhoA. However, the specific RhoGEF that
      translates CXCR4 signaling into RhoA activity and cell motility is unknown. We
      screened the three regulator of G-protein signaling RhoGEFs (LSC, LARG and PRG)
      and found that PRG selectively regulated the migration and invasion of CXCR4
      overexpressing breast tumor cells. Interestingly, we found that PDZ-RhoGEF (PRG)
      was required for spatial organization of F-actin structures in the center, but
      not periphery of the cells. The effects on the cytoskeleton were mirrored by the
      spatial effects on RhoA activity that were dependent upon PRG. Loss of PRG also
      enhanced adherens junctions in the epithelial-like MCF7-CXCR4 cell line, and
      inhibited directional persistence and polarity in the more mesenchymal MDA-MB-231
      cell line. Thus, PRG is essential for CXCR4-driven tumor cell migration through
      spatial regulation of RhoA and the subsequent organization of the cytoskeletal
      structures that support motility. Furthermore, immunohistochemical analysis of
      human breast tumor tissues shows a significant increase of PRG expression in the
      invasive areas of the tumors, suggesting that this RhoGEF is associated with
      breast tumor invasion in vivo.

PMID- 23868974
TI  - Formin-mediated actin polymerization cooperates with Mushroom body defect (Mud)
      Dynein during Frizzled-Dishevelled spindle orientation.
AB  - To position the mitotic spindle, cytoskeletal components must be coordinated to
      generate cortical forces on astral microtubules. Although the dynein motor is
      common to many spindle orientation systems, 'accessory pathways' are often also
      required. In this work, we identified an accessory spindle orientation pathway in
      Drosophila that functions with Dynein during planar cell polarity, downstream of
      the Frizzled (Fz) effector Dishevelled (Dsh). Dsh contains a PDZ ligand and a
      Dynein-recruiting DEP domain that are both required for spindle orientation. The
      Dsh PDZ ligand recruits Canoe/Afadin and ultimately leads to Rho GTPase signaling
      mediated through RhoGEF2. The formin Diaphanous (Dia) functions as the Rho
      effector in this pathway, inducing F-actin enrichment at sites of cortical Dsh.
      Chimeric protein experiments show that the Dia-actin accessory pathway can be
      replaced by an independent kinesin (Khc73) accessory pathway for Dsh-mediated
      spindle orientation. Our results define two 'modular' spindle orientation
      pathways and show an essential role for actin regulation in Dsh-mediated spindle
      orientation.

PMID- 23868976
TI  - Promoter occupancy of MLL1 histone methyltransferase seems to specify the
      proliferative and apoptotic functions of E2F1 in a tumour microenvironment.
AB  - The E2F family of transcription factors are considered versatile modulators,
      poised at biological crossroads to execute diverse cellular functions. Despite
      extensive studies on E2F, the molecular mechanisms that control specific
      biological functions of the E2F1 transcription factor are still not fully
      understood. Here we have addressed the molecular underpinnings of paradoxical
      functions of E2F1 in a tumour microenvironment using the 'X15-myc' oncomouse
      model of hepatocellular carcinoma. We observed that the HBx oncoprotein of
      hepatitis B virus regulates E2F1 functions by interfering with its binding to
      Skp2 E3 ubiquitin ligase. The HBx-Skp2 interaction led to the accumulation of
      transcriptionally active E2F1 and histone methyltransferase mixed lineage
      leukemia 1 (MLL1) protein. During early stages of hepatocarcinogenesis, the
      increased E2F1 activity promoted cellular proliferation by stimulating the genes
      involved in cell cycle control and replication. However, during the late stages,
      E2F1 triggered replication-stress-induced DNA damage and sensitized cells to
      apoptotic death in a p53-independent manner. Interestingly, the different
      promoter occupancy of MLL1 during the early and late stages of tumour development
      seemed to specify the proliferative and apoptotic functions of E2F1, through its
      dynamic interaction with the co-activator CBP or co-repressor Brg1. Thus, the
      temporally regulated promoter occupancy of histone methyltransferase could be a
      regulatory mechanism associated with the diverse cellular functions of the E2F
      family of transcription factors.

PMID- 23868975
TI  - Damage response of XRCC1 at sites of DNA single strand breaks is regulated by
      phosphorylation and ubiquitylation after degradation of poly(ADP-ribose).
AB  - Single-strand breaks (SSBs) are the most common type of oxidative DNA damage and
      they are related to aging and many genetic diseases. The scaffold protein for
      repair of SSBs, XRCC1, accumulates at sites of poly(ADP-ribose) (pAR) synthesized
      by PARP, but it is retained at sites of SSBs after pAR degradation. How XRCC1
      responds to SSBs after pAR degradation and how this affects repair progression
      are not well understood. We found that XRCC1 dissociates from pAR and is
      translocated to sites of SSBs dependent on its BRCTII domain and the function of
      PARG. In addition, phosphorylation of XRCC1 is also required for the proper
      dissociation kinetics of XRCC1 because (1) phosphorylation sites mutated in XRCC1
      (X1 pm) cause retention of XRCC1 at sites of SSB for a longer time compared to
      wild type XRCC1; and (2) phosphorylation of XRCC1 is required for efficient
      polyubiquitylation of XRCC1. Interestingly, a mutant of XRCC1, LL360/361DD, which
      abolishes pAR binding, shows significant upregulation of ubiquitylation,
      indicating that pARylation of XRCC1 prevents the poly-ubiquitylation. We also
      found that the dynamics of the repair proteins DNA polymerase beta, PNK, APTX,
      PCNA and ligase I are regulated by domains of XRCC1. In summary, the dynamic
      damage response of XRCC1 is regulated in a manner that depends on modifications
      of polyADP-ribosylation, phosphorylation and ubiquitylation in live cells.

PMID- 23868977
TI  - MiR-19b/20a/92a regulates the self-renewal and proliferation of gastric cancer
      stem cells.
AB  - Human gastric cancers contain a population of gastric cancer stem cells (GCSCs)
      that can undergo self-renewal and multipotent differentiation. GCSCs can be
      enriched with EpCAM+/CD44+ gastric cancer cells. However, the underlying
      mechanisms controlling the balance of GCSC self-renewal and differentiation
      remain to be explored. Because miRNAs can regulate cancer cell fates, we compared
      miRNA expression in tumorspheric cancer cells enriched with GCSCs and more
      differentiated cells. We found that the miR-17-92 cluster members miR-19b, miR
      20a and miR-92a were gradually reduced during the differentiation of GCSCs.
      Therefore, we speculated that miR-17-92 members might regulate the self-renewal
      ability of GCSCs. By downregulating miR-19b, miR-20a and miR-92a in EpCAM+/CD44+
      GCSCs, or overexpressing them in EpCAM-/CD44- non-GCSC populations, we found that
      miR-19b, miR-20a and miR-92a could sustain the self-renewal function of GCSCs.
      Furthermore, we found that miR-19b, miR-20a and miR-92a could also promote the
      proliferation of gastric cancer cells. miR-17-92 targeted the E2F1 and HIPK1
      proteins, which suppressed Wnt-beta-catenin signaling. A real-time PCR analysis
      of miR-19b, miR-20a and miR-92a expression in 97 gastric cancer specimens
      suggested that miR-92a could be used as an independent prognostic factor in
      gastric cancer. This study showed that several members of the miR-17-92 cluster,
      miR-19b, miR-20a and miR-92a, might play important roles in the development of
      gastric cancer stem cells and that miR-92a has the potential to be used as a
      predictive prognostic marker in gastric cancer.

PMID- 23868978
TI  - Kinesin-5 Kip1 is a bi-directional motor that stabilizes microtubules and tracks
      their plus-ends in vivo.
AB  - In this study, we examined the anaphase functions of the S. cerevisiae kinesin-5
      homolog Kip1. We show that Kip1 is attached to the mitotic spindle midzone during
      late anaphase. This attachment is essential to stabilize interpolar microtubule
      (iMTs) plus-ends. By detailed examination of iMT dynamics we show that at the end
      of anaphase, iMTs depolymerize in two stages: during the first stage, one pair of
      anti-parallel iMTs depolymerizes at a velocity of 7.7 um/minute; during the
      second stage, ~90 seconds later, the remaining pair of iMTs depolymerizes at a
      slower velocity of 5.4 um/minute. We show that upon the second depolymerization
      stage, which coincides with spindle breakdown, Kip1 follows the plus-ends of
      depolymerizing iMTs and translocates toward the spindle poles. This movement is
      independent of mitotic microtubule motor proteins or the major plus-end binding
      or tracking proteins. In addition, we show that Kip1 processively tracks the plus
      ends of growing and shrinking MTs, both inside and outside the nucleus. The plus
      end tracking activity of Kip1 requires its catalytic motor function, because a
      rigor mutant of Kip1 does not exhibit this activity. Finally, we show that Kip1
      is a bi-directional motor: in vitro, at high ionic strength conditions, single
      Kip1 molecules move processively in the minus-end direction of the MTs, whereas
      in a multi-motor gliding assay, Kip1 is plus-end directed. The bi-directionality
      and plus-end tracking activity of Kip1, properties revealed here for the first
      time, allow Kip1 to perform its multiple functions in mitotic spindle dynamics
      and to partition the 2-micron plasmid.

PMID- 23868979
TI  - Modelling of human Wiskott-Aldrich syndrome protein mutants in zebrafish larvae
      using in vivo live imaging.
AB  - Wiskott-Aldrich syndrome (WAS) and X-linked neutropenia (XLN) are
      immunodeficiencies in which the function of several haematopoietic cell lineages
      is perturbed as a result of mutations in the actin regulator WASp. From in vitro
      cell biology experiments, and biochemical and structural approaches, we know much
      about the functional domains of WASp and how WASp might regulate the dynamic
      actin cytoskeleton downstream of activators such as Cdc42, but in vivo
      experiments are much more challenging. In patients, there is a correlation
      between clinical disease and genotype, with severe reductions in WASp expression
      or function associating with complex multilineage immunodeficiency, whereas
      specific mutations that cause constitutive activation of WASp result in
      congenital neutropenia. Here, we take advantage of the genetic tractability and
      translucency of zebrafish larvae to first characterise how a null mutant in
      zfWASp influences the behaviour of neutrophils and macrophages in response to
      tissue damage and to clearance of infections. We then use this mutant background
      to study how leukocyte lineage-specific transgenic replacement with human WASp
      variants (including normal wild type and point mutations that either fail to bind
      Cdc42 or cannot be phosphorylated, and a constitutively active mutant equivalent
      to that seen in XLN patients) alter the capacity for generation of neutrophils,
      their chemotactic response to wounds and the phagocytic clearance capacity of
      macrophages. This model provides a unique insight into WASp-related
      immunodeficiency at both a cellular and whole organism level. 

PMID- 23868981
TI  - Regulation of EGFR trafficking and cell signaling by Sprouty2 and MIG6 in lung
      cancer cells.
AB  - The duration and specificity of epidermal growth factor receptor (EGFR)
      activation and signaling are determinants of cellular decision processes and are
      tightly regulated by receptor dephosphorylation, internalization and degradation.
      In addition, regulatory proteins that are upregulated or activated post
      transcriptionally upon receptor activation may initiate feedback loops that play
      crucial roles in spatiotemporal regulation of signaling. We examined the roles of
      Sprouty2 (SPRY2) and mitogen-inducible gene 6 (MIG6), two feedback regulators of
      EGFR trafficking and signaling, in lung cancer cells with or without EGFR
      activating mutations. These mutations are of interest because they confer unusual
      cellular sensitivity to EGFR inhibition through a mechanism involving an
      impairment of EGFR endocytosis. We found that the endocytosis of wild-type and
      mutant EGFR was promoted by SPRY2 knockdown and antagonized by MIG6 knockdown.
      SPRY2 knockdown also significantly reduced extracellular signal-regulated kinase
      (ERK) phosphorylation, EGFR expression, and EGFR recycling. In a cell line
      expressing mutant EGFR, this effect on ERK led to a marked increase in cell death
      response to EGFR inhibition. The effects of SPRY2 knockdown on EGFR endocytosis
      and recycling were primarily the result of the concomitant change in EGFR
      expression, but this was not true for the observed changes in ERK
      phosphorylation. Thus, our study demonstrates that SPRY2 and MIG6 are important
      regulators of wild-type and mutant EGFR trafficking and points to an EGFR
      expression-independent function of SPRY2 in the regulation of ERK activity that
      may impact cellular sensitivity to EGFR inhibitors, especially in the context of
      EGFR mutation.

PMID- 23868980
TI  - Src mediates the mechanical activation of myogenesis by activating TNFalpha
      converting enzyme.
AB  - Mechanical stimulation affects many biological aspects in living cells through
      mechanotransduction. In myogenic precursor cells (MPCs), mechanical stimulation
      activates p38 mitogen-activated protein kinase (MAPK), a key regulator of
      myogenesis, via activating TNFalpha-converting enzyme (TACE, also known as
      ADAM17), to release autocrine TNFalpha. However, the signaling mechanism of
      mechanical activation of TACE is unknown. Because TACE possesses the structural
      features of substrates of the non-receptor tyrosine kinase Src, we tested the
      hypothesis that Src mediates mechanical activation of TACE in MPCs. We observed
      that mechanical stretch of C2C12 or primary rat myoblasts rapidly activates Src,
      which in turn interacts and colocalizes with TACE, resulting in tyrosine
      phosphorylation and activation of TACE. Particularly, Src activates TACE via the
      phosphorylation of amino acid residue Tyr702 in the intracellular tail of TACE,
      resulting in increased TNFalpha release and p38 activation. Src inhibition or
      deficiency blocks stretch activation of the TACE-p38-MAPK signaling, resulting in
      impaired myogenic gene expression. In response to functional overloading, Src and
      TACE are activated in mouse soleus muscle. Further, overloading-induced
      myogenesis and regeneration are impaired in the soleus of Src(+/-) mice.
      Therefore, Src mediates mechano-activation of TACE and myogenesis.

PMID- 23868982
TI  - Two potential calmodulin-binding sequences in the ryanodine receptor contribute
      to a mobile, intra-subunit calmodulin-binding domain.
AB  - Calmodulin (CaM), a 16 kDa ubiquitous calcium-sensing protein, is known to bind
      tightly to the calcium release channel/ryanodine receptor (RyR), and modulate RyR
      function. CaM binding studies using RyR fragments or synthetic peptides have
      revealed the presence of multiple, potential CaM-binding regions in the primary
      sequence of RyR. In the present study, we inserted GFP into two of these proposed
      CaM-binding sequences and mapped them onto the three-dimensional structure of
      intact cardiac RyR2 by cryo-electron microscopy. Interestingly, we found that the
      two potential CaM-binding regions encompassing, Arg3595 and Lys4269,
      respectively, are in close proximity and are adjacent to the previously mapped
      CaM-binding sites. To monitor the conformational dynamics of these CaM-binding
      regions, we generated a fluorescence resonance energy transfer (FRET) pair, a
      dual CFP- and YFP-labeled RyR2 (RyR2R3595-CFP/K4269-YFP) with CFP inserted after
      Arg3595 and YFP inserted after Lys4269. We transfected HEK293 cells with the
      RyR2R3595-CFP/K4269-YFP cDNA, and examined their FRET signal in live cells. We
      detected significant FRET signals in transfected cells that are sensitive to the
      channel activator caffeine, suggesting that caffeine is able to induce
      conformational changes in these CaM-binding regions. Importantly, no significant
      FRET signals were detected in cells co-transfected with cDNAs encoding the single
      CFP (RyR2R3595-CFP) and single YFP (RyR2K4269-YFP) insertions, indicating that
      the FRET signal stemmed from the interaction between R3595-CFP and K4269-YFP that
      are in the same RyR subunit. These observations suggest that multiple regions in
      the RyR2 sequence may contribute to an intra-subunit CaM-binding pocket that
      undergoes conformational changes during channel gating.

PMID- 23868983
TI  - Selection of Phototransduction Genes in Homo sapiens.
AB  - PURPOSE: We investigated the evidence of recent positive selection in the human
      phototransduction system at single nucleotide polymorphism (SNP) and gene level.
      METHODS: SNP genotyping data from the International HapMap Project for European,
      Eastern Asian, and African populations was used to discover differences in
      haplotype length and allele frequency between these populations. Numeric
      selection metrics were computed for each SNP and aggregated into gene-level
      metrics to measure evidence of recent positive selection. The level of recent
      positive selection in phototransduction genes was evaluated and compared to a set
      of genes shown previously to be under recent selection, and a set of highly
      conserved genes as positive and negative controls, respectively. RESULTS: Six of
      20 phototransduction genes evaluated had gene-level selection metrics above the
      90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal
      across these genes was found to be of similar magnitude to the positive control
      genes and much greater than the negative control genes. CONCLUSIONS: There is
      evidence for selective pressure in the genes involved in retinal
      phototransduction, and traces of this selective pressure can be demonstrated
      using SNP-level and gene-level metrics of allelic variation. We hypothesize that
      the selective pressure on these genes was related to their role in low light
      vision and retinal adaptation to ambient light changes. Uncovering the underlying
      genetics of evolutionary adaptations in phototransduction not only allows greater
      understanding of vision and visual diseases, but also the development of patient
      specific diagnostic and intervention strategies.

PMID- 23868984
TI  - IGFBP-3 and TNF-alpha regulate retinal endothelial cell apoptosis.
AB  - PURPOSE: We hypothesized that loss of insulin-like growth factor binding protein
      3 (IGFBP-3) signaling would produce neuronal changes in the retina similar to
      early diabetes. METHODS: To understand better the role of IGFBP-3 in the retina,
      IGFBP-3 knockout (KO) mice were evaluated for neuronal, vascular, and functional
      changes compared to wild-type littermates. We also cultured retinal endothelial
      cells (REC) in normoglycemia or hyperglycemia to determine the interaction
      between IGFBP-3 and TNF-alpha, as data indicate that both proteins are regulated
      by beta-adrenergic receptors and respond antagonistically. We also treated some
      cells with Compound 49b, a novel beta-adrenergic receptor agonist we have
      reported previously to regulate IGFBP-3 and TNF-alpha. RESULTS: Electroretinogram
      analyses showed decreased B-wave and oscillatory potential amplitudes in the
      IGFBP-3 KO mice, corresponding to increased apoptosis. Retinal thickness and cell
      numbers in the ganglion cell layer were reduced in the IGFBP-3 KO mice. As
      expected, loss of IGFBP-3 was associated with increased TNF-alpha levels. When
      TNF-alpha and IGFBP-3 were applied to REC, they worked antagonistically, with
      IGFBP-3 inhibiting apoptosis and TNF-alpha promoting apoptosis. Due to their
      antagonistic nature, results suggest that apoptosis of REC may depend upon which
      protein (IGFBP-3 versus TNF-alpha) is active. CONCLUSIONS: Taken together, loss
      of IGFBP-3 signaling results in a phenotype similar to neuronal changes observed
      in diabetic retinopathy in the early phases, including increased TNF-alpha
      levels.

PMID- 23868985
TI  - Establishment of a human corneal epithelial cell line lacking the functional
      TACSTD2 gene as an in vitro model for gelatinous drop-like dystrophy.
AB  - PURPOSE: Gelatinous drop-like corneal dystrophy (GDLD) is characterized by
      subepithelial amyloid deposition that engenders severe vision loss. The exact
      mechanism of this disease has yet to be elucidated. No fundamental treatment
      exists. This study was conducted to establish an immortalized corneal epithelial
      cell line to be used as a GDLD disease model. METHODS: A corneal tissue specimen
      was obtained from a GDLD patient during surgery. Corneal epithelial cells were
      enzymatically separated from the cornea and were dissociated further into single
      cells. The epithelial cells were immortalized by the lentiviral transduction of
      the simian virus 40 (SV40) large T antigen and human telomerase reverse
      transcriptase (hTERT) genes. For the immortalized cells, proliferative kinetics,
      gene expressions, and functional analyses were performed. RESULTS: The
      immortalized corneal epithelial cells continued to proliferate despite cumulative
      population doubling that exceeded 100. The cells showed almost no sign of
      senescence and displayed strong colony-forming activity. The cells exhibited a
      low epithelial barrier function as well as decreased expression of tight-junction
      related proteins claudin 1 and 7. Using the immortalized corneal epithelial cells
      derived from a GDLD patient, we tested the possibility of gene therapy.
      CONCLUSIONS: We established an immortalized corneal epithelial cell line from a
      GDLD patient. The immortalized cells exhibited cellular phenotypes similar to
      those of in vivo GDLD. The immortalized cells are thought to be useful for the
      development of new therapies for treating GDLD corneas and for elucidation of the
      pathophysiology of GDLD.

PMID- 23868986
TI  - Development of latanoprost-loaded biodegradable nanosheet as a new drug delivery
      system for glaucoma.
AB  - PURPOSE: We investigated the IOP reduction and safety of latanoprost-loaded
      biodegradable nanosheet (LBNS) as a new antiglaucoma drug delivery system (DDS).
      METHODS: We fabricated a 40 nm thick multilayered biodegradable nanosheet that is
      composed of chitosan and sodium alginate by means of the layer-by-layer method.
      Latanoprost isopropyl ester was loaded on the nanosheet to prepare 25, 2.5, and
      0.25 MUg/cm(2) LBNSs. A nanosheet without latanoprost isopropyl ester (NS) and
      0.005% latanoprost ophthalmic solution were prepared as controls. LBNSs or NS was
      applied to rat cornea, and IOP was monitored for 9 days. Local adverse effects
      and eye scratching movement also were investigated. The amount of latanoprost
      acid in aqueous humor and was measured in rabbits. RESULTS: The 0.25 MUg/cm(2)
      LBNS and 0.005% latanoprost ophthalmic solution showed significant IOP reduction
      only for 1 day after application, whereas the IOP reduction rates of 2.5
      MUg/cm(2) LBNS at 1, 2, 4, 7, and 9 days after application were -27.0% +/- 14.8%,
      -22.0% +/- 16.7%, -25.8% +/- 18.0%, -22.7% +/- 20.9%, and -6.6% +/- 17.0%,
      respectively. The 25 MUg/cm(2) LBNS reduced IOP in a similar manner. The 25
      MUg/cm(2) LBNS induced transient hyperemia, whereas the 0.25 and 2.5 MUg/cm(2)
      LBNSs did not exert any local adverse effects. The eye scratching movement test
      showed that application of 25 MUg/cm(2) LBNS did not cause any irritation of the
      eye. Latanoprost acid was detected in aqueous humor up to 6 days after
      application of 2.5 MUg/cm(2) LBNS. CONCLUSIONS: LBNS may be used as a novel
      antiglaucoma DDS.

PMID- 23868987
TI  - Pathways for conservation.

PMID- 23868992
TI  - Japan. Tampered data cast shadow on drug trial.

PMID- 23868993
TI  - Anthropology. Latest skirmish over ancestral violence strikes blow for peace.

PMID- 23868994
TI  - Spain. Spain's research council approaches bankruptcy.

PMID- 23868995
TI  - Microbiology. Ever-bigger viruses shake tree of life.

PMID- 23868996
TI  - Funding. Germany debates how to strengthen universities.

PMID- 23868997
TI  - Space science. Mars rover plans roll while asteroid acrimony continues.

PMID- 23868998
TI  - Battle for the Americas.

PMID- 23868999
TI  - Salvage paleontology on the seaway.

PMID- 23869000
TI  - Biodiversity. The Amazon in 4D.

PMID- 23869001
TI  - Turkey must end violent response to protests.

PMID- 23869002
TI  - Optimizing peer review of software code.

PMID- 23869003
TI  - Optimizing peer review of software code--response.

PMID- 23869006
TI  - Response to comments on "Can we name Earth's species before they go extinct?".
AB  - Mora et al. disputed that most species will be discovered before they go extinct,
      but not our main recommendations to accelerate species' discoveries. We show that
      our conclusions would be unaltered by discoveries of more microscopic species and
      reinforce our estimates of species description and extinction rates, that
      taxonomic effort has never been greater, and that there are 2 to 8 million
      species on Earth. 

PMID- 23869005
TI  - Comment on "Can we name Earth's species before they go extinct?".
AB  - Costello et al. (Review, 25 January 2013, p. 413) challenged the common view that
      many species are disappearing before being described. We suggest that their
      conclusion is overly optimistic because of a limited selection and interpretation
      of available evidence that tends to overestimate rates of species description and
      underestimate the number of species on Earth and their current extinction rate. 

PMID- 23869007
TI  - Science education. Crowdsourcing and curating online education resources.

PMID- 23869008
TI  - Cell biology. Trans-HSF1 express.

PMID- 23869009
TI  - Materials science. Droplets out of equilibrium.

PMID- 23869010
TI  - Developmental biology. Enhancing pluripotency and lineage specification.

PMID- 23869011
TI  - Engineering. Multiscale design and integration of sustainable building functions.

PMID- 23869012
TI  - Switchable static and dynamic self-assembly of magnetic droplets on
      superhydrophobic surfaces.
AB  - Self-assembly is a process in which interacting bodies are autonomously driven
      into ordered structures. Static structures such as crystals often form through
      simple energy minimization, whereas dynamic ones require continuous energy input
      to grow and sustain. Dynamic systems are ubiquitous in nature and biology but
      have proven challenging to understand and engineer. Here, we bridge the gap from
      static to dynamic self-assembly by introducing a model system based on ferrofluid
      droplets on superhydrophobic surfaces. The droplets self-assemble under a static
      external magnetic field into simple patterns that can be switched to complicated
      dynamic dissipative structures by applying a time-varying magnetic field. The
      transition between the static and dynamic patterns involves kinetic trapping and
      shows complexity that can be directly visualized. 

PMID- 23869015
TI  - Lethal aggression in mobile forager bands and implications for the origins of
      war.
AB  - It has been argued that warfare evolved as a component of early human behavior
      within foraging band societies. We investigated lethal aggression in a sample of
      21 mobile forager band societies (MFBS) derived systematically from the standard
      cross-cultural sample. We hypothesized, on the basis of mobile forager
      ethnography, that most lethal events would stem from personal disputes rather
      than coalitionary aggression against other groups (war). More than half of the
      lethal aggression events were perpetrated by lone individuals, and almost two
      thirds resulted from accidents, interfamilial disputes, within-group executions,
      or interpersonal motives such as competition over a particular woman. Overall,
      the findings suggest that most incidents of lethal aggression among MFBS may be
      classified as homicides, a few others as feuds, and a minority as war. 

PMID- 23869016
TI  - Loss of function of the melanocortin 2 receptor accessory protein 2 is associated
      with mammalian obesity.
AB  - Melanocortin receptor accessory proteins (MRAPs) modulate signaling of
      melanocortin receptors in vitro. To investigate the physiological role of brain
      expressed melanocortin 2 receptor accessory protein 2 (MRAP2), we characterized
      mice with whole-body and brain-specific targeted deletion of Mrap2, both of which
      develop severe obesity at a young age. Mrap2 interacts directly with melanocortin
      4 receptor (Mc4r), a protein previously implicated in mammalian obesity, and it
      enhances Mc4r-mediated generation of the second messenger cyclic adenosine
      monophosphate, suggesting that alterations in Mc4r signaling may be one mechanism
      underlying the association between Mrap2 disruption and obesity. In a study of
      humans with severe, early-onset obesity, we found four rare, potentially
      pathogenic genetic variants in MRAP2, suggesting that the gene may also
      contribute to body weight regulation in humans. 

PMID- 23869017
TI  - Developmental control of the melanocortin-4 receptor by MRAP2 proteins in
      zebrafish.
AB  - The melanocortin-4 receptor (MC4R) is essential for control of energy homeostasis
      in vertebrates. MC4R interacts with melanocortin receptor accessory protein 2
      (MRAP2) in vitro, but its functions in vivo are unknown. We found that MRAP2a, a
      larval form, stimulates growth of zebrafish by specifically blocking the action
      of MC4R. In cell culture, this protein binds MC4R and reduces the ability of the
      receptor to bind its ligand, alpha-melanocyte-stimulating hormone (alpha-MSH). A
      paralog, MRAP2b, expressed later in development, also binds MC4R but increases
      ligand sensitivity. Thus, MRAP2 proteins allow for developmental control of MC4R
      activity, with MRAP2a blocking its function and stimulating growth during larval
      development, whereas MRAP2b enhances responsiveness to alpha-MSH once the
      zebrafish begins feeding, thus increasing the capacity for regulated feeding and
      growth. 

PMID- 23869018
TI  - Pandoraviruses: amoeba viruses with genomes up to 2.5 Mb reaching that of
      parasitic eukaryotes.
AB  - Ten years ago, the discovery of Mimivirus, a virus infecting Acanthamoeba,
      initiated a reappraisal of the upper limits of the viral world, both in terms of
      particle size (>0.7 micrometers) and genome complexity (>1000 genes), dimensions
      typical of parasitic bacteria. The diversity of these giant viruses (the
      Megaviridae) was assessed by sampling a variety of aquatic environments and their
      associated sediments worldwide. We report the isolation of two giant viruses, one
      off the coast of central Chile, the other from a freshwater pond near Melbourne
      (Australia), without morphological or genomic resemblance to any previously
      defined virus families. Their micrometer-sized ovoid particles contain DNA
      genomes of at least 2.5 and 1.9 megabases, respectively. These viruses are the
      first members of the proposed "Pandoravirus" genus, a term reflecting their lack
      of similarity with previously described microorganisms and the surprises expected
      from their future study. 

PMID- 23869013
TI  - Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere.
AB  - Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of
      planetary geophysical processes, and for Mars they reveal the record of loss of
      its atmosphere and subsequent interactions with its surface such as carbonate
      formation. We report in situ measurements of the isotopic ratios of D/H and
      (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and
      (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale
      Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable
      laser spectrometer (TLS). Comparison between our measurements in the modern
      atmosphere and those of martian meteorites such as ALH 84001 implies that the
      martian reservoirs of CO2 and H2O were largely established ~4 billion years ago,
      but that atmospheric loss or surface interaction may be still ongoing. 

PMID- 23869019
TI  - Exceptional convergence on the macroevolutionary landscape in island lizard
      radiations.
AB  - G. G. Simpson, one of the chief architects of evolutionary biology's modern
      synthesis, proposed that diversification occurs on a macroevolutionary adaptive
      landscape, but landscape models are seldom used to study adaptive divergence in
      large radiations. We show that for Caribbean Anolis lizards, diversification on
      similar Simpsonian landscapes leads to striking convergence of entire faunas on
      four islands. Parallel radiations unfolding at large temporal scales shed light
      on the process of adaptive diversification, indicating that the adaptive
      landscape may give rise to predictable evolutionary patterns in nature, that
      adaptive peaks may be stable over macroevolutionary time, and that available
      geographic area influences the ability of lineages to discover new adaptive
      peaks. 

PMID- 23869020
TI  - Predicting and manipulating cardiac drug inactivation by the human gut bacterium
      Eggerthella lenta.
AB  - Despite numerous examples of the effects of the human gastrointestinal microbiome
      on drug efficacy and toxicity, there is often an incomplete understanding of the
      underlying mechanisms. Here, we dissect the inactivation of the cardiac drug
      digoxin by the gut Actinobacterium Eggerthella lenta. Transcriptional profiling,
      comparative genomics, and culture-based assays revealed a cytochrome-encoding
      operon up-regulated by digoxin, inhibited by arginine, absent in nonmetabolizing
      E. lenta strains, and predictive of digoxin inactivation by the human gut
      microbiome. Pharmacokinetic studies using gnotobiotic mice revealed that dietary
      protein reduces the in vivo microbial metabolism of digoxin, with significant
      changes to drug concentration in the serum and urine. These results emphasize the
      importance of viewing pharmacology from the perspective of both our human and
      microbial genomes. 

PMID- 23869014
TI  - Abundance and isotopic composition of gases in the martian atmosphere from the
      Curiosity rover.
AB  - Volume mixing and isotope ratios secured with repeated atmospheric measurements
      taken with the Sample Analysis at Mars instrument suite on the Curiosity rover
      are: carbon dioxide (CO2), 0.960(+/-0.007); argon-40 ((40)Ar), 0.0193(+/-0.0001);
      nitrogen (N2), 0.0189(+/-0.0003); oxygen, 1.45(+/-0.09) * 10(-3); carbon
      monoxide, < 1.0 * 10(-3); and (40)Ar/(36)Ar, 1.9(+/-0.3) * 10(3). The (40)Ar/N2
      ratio is 1.7 times greater and the (40)Ar/(36)Ar ratio 1.6 times lower than
      values reported by the Viking Lander mass spectrometer in 1976, whereas other
      values are generally consistent with Viking and remote sensing observations. The
      (40)Ar/(36)Ar ratio is consistent with martian meteoritic values, which provides
      additional strong support for a martian origin of these rocks. The isotopic
      signature delta(13)C from CO2 of ~45 per mil is independently measured with two
      instruments. This heavy isotope enrichment in carbon supports the hypothesis of
      substantial atmospheric loss. 

PMID- 23869021
TI  - Applications of acceptorless dehydrogenation and related transformations in
      chemical synthesis.
AB  - Conventional oxidations of organic compounds formally transfer hydrogen atoms
      from the substrate to an acceptor molecule such as oxygen, a metal oxide, or a
      sacrificial olefin. In acceptorless dehydrogenation (AD) reactions, catalytic
      scission of C-H, N-H, and/or O-H bonds liberates hydrogen gas with no need for a
      stoichiometric oxidant, thereby providing efficient, nonpolluting activation of
      substrates. In addition, the hydrogen gas is valuable in itself as a high-energy,
      clean fuel. Here, we review AD reactions selectively catalyzed by transition
      metal complexes, as well as related transformations that rely on intermediates
      derived from reversible dehydrogenation. We delineate the methodologies evolving
      from this recent concept and highlight the effect of these reactions on chemical
      synthesis. 

PMID- 23869023
TI  - Age-dependent elevations in plasma kisspeptin are observed in boys and girls when
      compared with adults.
AB  - BACKGROUND: Kisspeptin is a hypothalamic neuropeptide playing a physiological
      role in human reproduction. Genetic over-activation of kisspeptin causes
      precocious puberty in children. Concentrations of circulating kisspeptin are low
      in adults. The concentrations of plasma kisspeptin in boys and girls have not
      been studied previously. METHODS: Blood was obtained from 51 children and 63
      adults. Plasma samples were analysed using radioimmunoassay. Children were aged 2
      18 years, and attending hospital for a medically requested blood test unrelated
      to reproductive development. Data on pubertal status were not collected due to
      ethical reasons. RESULTS: Mean plasma kisspeptin was significantly higher in
      children when compared with adults (mean plasma kisspeptin in pmol/L: 12.3 +/-
      0.9, adults; 40.9 +/- 3.3, children, P < 0.001 vs. adults). Overall mean
      concentrations of plasma kisspeptin were not significantly different between
      sexes (mean plasma kisspeptin in pmol/L: 39.5 +/- 3.2, boys; 44.3 +/- 6.3, girls,
      P = 0.48). In both sexes, concentrations of plasma kisspeptin increased with age
      to peak concentrations between 9 and 12 years of age, before decreasing beyond 12
      years of age to adulthood. Plasma kisspeptin concentrations were highly
      significantly elevated in both girls and boys aged 9-12 when compared with adults
      (mean plasma kisspeptin in pmol/L: 59.5 +/- 18.3, girls, P < 0.01 vs. adult
      women; 43.8 +/- 6.2, boys, P < 0.001 vs. adult men). CONCLUSIONS: We report that
      circulating kisspeptin is elevated in both boys and girls when compared with
      adults. Furthermore both boys and girls may have distinct, age-dependent
      concentrations of circulating kisspeptin. Further studies may determine if plasma
      kisspeptin could be used as a clinically useful biochemical marker of
      reproductive development in children.

PMID- 23869022
TI  - Tight coordination of protein translation and HSF1 activation supports the
      anabolic malignant state.
AB  - The ribosome is centrally situated to sense metabolic states, but whether its
      activity, in turn, coherently rewires transcriptional responses is unknown. Here,
      through integrated chemical-genetic analyses, we found that a dominant
      transcriptional effect of blocking protein translation in cancer cells was
      inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional
      regulator of the heat-shock response and many other cellular processes essential
      for anabolic metabolism, cellular proliferation, and tumorigenesis. These
      analyses linked translational flux to the regulation of HSF1 transcriptional
      activity and to the modulation of energy metabolism. Targeting this link with
      translation initiation inhibitors such as rocaglates deprived cancer cells of
      their energy and chaperone armamentarium and selectively impaired the
      proliferation of both malignant and premalignant cells with early-stage oncogenic
      lesions. 

PMID- 23869024
TI  - Correlation of fractalkine concentrations in serum and synovial fluid with the
      radiographic severity of knee osteoarthritis.
AB  - BACKGROUND: Fractalkine has been detected in synovial fluid (SF) from
      osteoarthritis (OA) patients. This study aims to examine the relation of
      fractalkine concentrations in serum and SF with the radiographic severity of OA.
      METHODS: Fractalkine concentrations of serum and SF were measured using an enzyme
      linked immunosorbent assay method in 223 patients with knee OA and 165 healthy
      controls. The progression of OA was classified according to the Kellgren-Lawrence
      grading system. RESULTS: Elevated concentrations of fractalkine in serum were
      found in knee OA patients compared with healthy controls [all results median
      (interquartile range) 226.25 (183.19-259.91) vs. 127.42 (99.54-154.98) pg/mL, P <
      0.001]. The case group included 71 knee OA patients with grade 2, 98 with grade
      3, and 54 with grade 4. Knee OA patients with KL grade 4 had significantly higher
      fractalkine concentrations in serum and SF compared with those with KL grade 2
      and 3 [serum: 247.68 (215.05-278.64) vs. 212.45 (169.19-247.96) pg/mL, P < 0.001,
      and 247.68 (215.05-278.64) vs. 222.00 (179.80-254.98) pg/mL, P = 0.005,
      respectively; SF: 94.95 (76.46-106.68) vs. 74.31 (63.64-84.79) pg/mL, P < 0.001,
      and 94.95 (76.46-106.68) vs. 80.34 (68.84-96.39) pg/mL, P = 0.001, respectively].
      Knee OA patients with KL grade 3 showed significantly elevated concentrations of
      fractalkine in SF compared with those with KL grade 2 [80.34 (68.84-96.39) vs.
      74.31 (63.64-84.79) pg/mL, P = 0.004]. Fractalkine concentrations in serum and SF
      of knee OA patients were both significantly associated with the disease severity
      evaluated by KL grading criteria (r = 0.261, P < 0.001 and r = 0.366, P < 0.001,
      respectively). CONCLUSION: The fractalkine concentrations in serum and SF may
      serve as an effective biomarker for the severity of OA.

PMID- 23869025
TI  - Evaluation of various deformable image registration algorithms for thoracic
      images.
AB  - We evaluated the accuracy of one commercially available and three publicly
      available deformable image registration (DIR) algorithms for thoracic four
      dimensional (4D) computed tomography (CT) images. Five patients with esophagus
      cancer were studied. Datasets of the five patients were provided by DIR-lab (dir
      lab.com) and consisted of thoracic 4D CT images and a coordinate list of
      anatomical landmarks that had been manually identified. Expert landmark
      correspondence was used for evaluating DIR spatial accuracy. First, the manually
      measured displacement vector field (mDVF) was obtained from the coordinate list
      of anatomical landmarks. Then the automatically calculated displacement vector
      field (aDVF) was calculated by using the following four DIR algorithms: B-spine
      implemented in Velocity AI (Velocity Medical, Atlanta, GA, USA), free-form
      deformation (FFD), Horn-Schunk optical flow (OF) and Demons in DIRART of MATLAB
      software. Registration error is defined as the difference between mDVF and aDVF.
      The mean 3D registration errors were 2.7 +/- 0.8 mm for B-spline, 3.6 +/- 1.0 mm
      for FFD, 2.4 +/- 0.9 mm for OF and 2.4 +/- 1.2 mm for Demons. The results showed
      that reasonable accuracy was achieved in B-spline, OF and Demons, and that these
      algorithms have the potential to be used for 4D dose calculation, automatic image
      segmentation and 4D CT ventilation imaging in patients with thoracic cancer.
      However, for all algorithms, the accuracy might be improved by using the
      optimized parameter setting. Furthermore, for B-spline in Velocity AI, the 3D
      registration error was small with displacements of less than ~10 mm, indicating
      that this software may be useful in this range of displacements. 

PMID- 23869026
TI  - Potentiating mGluR5 function with a positive allosteric modulator enhances
      adaptive learning.
AB  - Metabotropic glutamate receptor 5 (mGluR5) plays important roles in modulating
      neural activity and plasticity and has been associated with several
      neuropathological disorders. Previous work has shown that genetic ablation or
      pharmacological inhibition of mGluR5 disrupts fear extinction and spatial
      reversal learning, suggesting that mGluR5 signaling is required for different
      forms of adaptive learning. Here, we tested whether ADX47273, a selective
      positive allosteric modulator (PAM) of mGluR5, can enhance adaptive learning in
      mice. We found that systemic administration of the ADX47273 enhanced reversal
      learning in the Morris Water Maze, an adaptive task. In addition, we found that
      ADX47273 had no effect on single-session and multi-session extinction, but
      administration of ADX47273 after a single retrieval trial enhanced subsequent
      fear extinction learning. Together these results demonstrate a role for mGluR5
      signaling in adaptive learning, and suggest that mGluR5 PAMs represent a viable
      strategy for treatment of maladaptive learning and for improving behavioral
      flexibility. 

PMID- 23869028
TI  - Whose "best interests" are at stake?

PMID- 23869027
TI  - Active vs. reactive threat responding is associated with differential c-Fos
      expression in specific regions of amygdala and prefrontal cortex.
AB  - Active avoidance (AA) is an important paradigm for studying mechanisms of
      aversive instrumental learning, pathological anxiety, and active coping.
      Unfortunately, AA neurocircuits are poorly understood, partly because behavior is
      highly variable and reflects a competition between Pavlovian reactions and
      instrumental actions. Here we exploited the behavioral differences between good
      and poor avoiders to elucidate the AA neurocircuit. Rats received Sidman AA
      training and expression of the activity-dependent immediate-early gene c-fos was
      measured after a shock-free AA test. Six brain regions with known or putative
      roles in AA were evaluated: amygdala, periaqueductal gray, nucleus accumbens,
      dorsal striatum, prefrontal cortex (PFC), and hippocampus. Good avoiders showed
      little Pavlovian freezing and high AA rates at test, the opposite of poor
      avoiders. Although c-Fos activation was observed throughout the brain,
      differential activation was found only in subregions of amygdala and PFC.
      Interestingly, c-Fos correlated with avoidance and freezing in only five of 20
      distinct areas evaluated: lateral amygdala, central amygdala, medial amygdala,
      basal amygdala, and infralimbic PFC. Thus, activity in specific amygdala-PFC
      circuits likely mediates the competition between instrumental actions and
      Pavlovian reactions after AA training. Individual differences in AA behavior,
      long considered a nuisance by researchers, may be the key to elucidating the AA
      neurocircuit and understanding pathological response profiles. 

PMID- 23869029
TI  - Predictors of suffering in advanced cancer.
AB  - CONTEXT: Suffering is a complex experience. Identifying its predictors is useful
      to signal at-risk patients. OBJECTIVE: To identify suffering predictors in
      patients with advanced cancer in palliative care. METHODS: A total of 98 patients
      participated in the study. A semistructured interview examining suffering levels
      and physical, psychological, social, and spiritual aspects was used. Instruments
      included Pictorial Representation of Illness and Self Measure (PRISM), Edmonton
      Symptom Assessment System (ESAS), Detection of emotional distress (DED), and
      Structured Interview of Symptoms and Concern (SISC). Variance-based structural
      equation model was used for the data analysis. RESULTS: All measures were valid
      and reliable. The structural model explained 64% of the variance. Suffering
      levels were directly determined by psychological and adjustment problems and
      indirectly determined by physical, psychological, and spiritual aspects and
      coping strategies. CONCLUSION: Our study supports the proposed theoretical model
      and signals the important mediating effect of psychological and spiritual
      variables between physical symptoms and suffering.

PMID- 23869030
TI  - Psychiatric characteristics in transsexual individuals: multicentre study in four
      European countries.
AB  - BACKGROUND: Research into the relationship between gender identity disorder and
      psychiatric problems has shown contradictory results. AIMS: To investigate
      psychiatric problems in adults fulfilling DSM-IV-TR criteria for a diagnosis of
      gender identity disorder. METHOD: Data were collected within the European Network
      for the Investigation of Gender Incongruence using the Mini International
      Neuropsychiatric Interview - Plus and the Structured Clinical Interview for DSM
      IV Axis II Disorders (n = 305). RESULTS: In 38% of the individuals with gender
      identity disorder a current DSM-IV-TR Axis I diagnosis was found, mainly
      affective disorders and anxiety disorders. Furthermore, almost 70% had a current
      and lifetime diagnosis. All four countries showed a similar prevalence, except
      for affective and anxiety disorders, and no difference was found between
      individuals with early-onset and late-onset disorder. An Axis II diagnosis was
      found in 15% of all individuals with gender identity disorder, which is
      comparable to the general population. CONCLUSIONS: People with gender identity
      disorder show more psychiatric problems than the general population; mostly
      affective and anxiety problems are found.

PMID- 23869033
TI  - Authors' reply.

PMID- 23869043
TI  - Authors' reply.

PMID- 23869046
TI  - Medical expertise, existential suffering and ending life.
AB  - In this article, I assess the position that voluntary euthanasia (VE) and
      physician-assisted suicide (PAS) ought not to be accepted in the cases of persons
      who suffer existentially but who have no medical condition, because existential
      questions do not fall within the domain of physicians' professional expertise. I
      maintain that VE and PAS based on suffering arising from medical conditions
      involves existential issues relevantly similar to those confronted in connection
      with existential suffering. On that basis I conclude that if VE and PAS based on
      suffering arising from medical conditions is taken to fall within the domain of
      medical expertise, it is not consistent to use the view that physicians'
      professional expertise does not extend to existential questions as a reason for
      denying requests for VE and PAS from persons who suffer existentially but have no
      medical condition. 

PMID- 23869047
TI  - 'Existential suffering' and voluntary medically assisted dying.

PMID- 23869045
TI  - Proteomic analysis of eggs from Mytilus edulis females differing in mitochondrial
      DNA transmission mode.
AB  - Many bivalves have an unusual mechanism of mitochondrial DNA (mtDNA) inheritance
      called doubly uniparental inheritance (DUI) in which distinctly different genomes
      are inherited through the female (F genome) and male (M genome) lineages. In
      fertilized eggs that will develop into male embryos, the sperm mitochondria
      remain in an aggregation, which is believed to be delivered to the primordial
      germ cells and passed to the next generation through the sperm. In fertilized
      eggs that will develop into female embryos, the sperm mitochondria are dispersed
      throughout the developing embryo and make little if any contribution to the next
      generation. The frequency of embryos with the aggregated or dispersed
      mitochondrial type varies among females. Previous models of DUI have predicted
      that maternal nuclear factors cause molecular differences among unfertilized eggs
      from females producing embryos with predominantly dispersed or aggregated
      mitochondria. We test this hypothesis using females of each of the two types from
      a natural population. We have found small, yet detectable, differences of the
      predicted type at the proteome level. We also provide evidence that eggs of
      females giving the dispersed pattern have consistently lower expression for
      different proteasome subunits than eggs of females giving the aggregated pattern.
      These results, combined with those of an earlier study in which we used hatchery
      lines of Mytilus, and with a transcriptomic study in a clam that has the DUI
      system of mtDNA transmission, reinforce the hypothesis that the ubiquitin
      proteasome system plays a key role in the mechanism of DUI and sex determination
      in bivalves. We also report that eggs of females giving the dispersed pattern
      have higher expression for arginine kinase and enolase, enzymes involved in
      energy production, whereas ferritin, which is involved in iron homeostasis, has
      lower expression. We discuss these results in the context of genetic models for
      DUI and suggest experimental methods for further understanding the role of these
      proteins in DUI. 

PMID- 23869048
TI  - A simple solution to the puzzles of end of life? Voluntary palliated starvation.

PMID- 23869049
TI  - Current and emergent strategies for disinfection of hospital environments.
AB  - A significant number of hospital-acquired infections occur due to inefficient
      disinfection of hospital surfaces, instruments and rooms. The emergence and wide
      spread of multiresistant forms of several microorganisms has led to a situation
      where few compounds are able to inhibit or kill the infectious agents. Several
      strategies to disinfect both clinical equipment and the environment are
      available, often involving the use of antimicrobial chemicals. More recently,
      investigations into gas plasma, antimicrobial surfaces and vapour systems have
      gained interest as promising alternatives to conventional disinfectants. This
      review provides updated information on the current and emergent disinfection
      strategies for clinical environments. 

PMID- 23869050
TI  - Pharmacokinetics and pharmacodynamics of extended-infusion
      piperacillin/tazobactam in adult patients with cystic fibrosis-related acute
      pulmonary exacerbations.
AB  - OBJECTIVES: Given the high frequency of acute pulmonary exacerbations due to
      Pseudomonas aeruginosa in patients with cystic fibrosis (CF),
      piperacillin/tazobactam is commonly used in empirical regimens. While extended
      infusion piperacillin/tazobactam has been employed as one strategy to optimize
      this agent's pharmacodynamics, this approach has not been well characterized in
      patients with CF. The objectives of this study were to characterize the
      pharmacokinetics and pharmacodynamics of extended-infusion
      piperacillin/tazobactam in adult patients with CF and derive optimized
      piperacillin/tazobactam dosing recommendations. METHODS: Six serum samples were
      collected from nine adult patients with CF hospitalized for acute pulmonary
      exacerbations who received 3/0.375 g of piperacillin/tazobactam intravenously for
      4 h every 8 h. Population pharmacokinetic models were fitted to the data
      utilizing first-order, Michaelis-Menten (MM) and parallel first-order/MM
      clearance. Monte Carlo simulations were performed to determine the probability of
      target attainment (PTA) for regimens where free piperacillin concentrations were
      above the MIC for at least 50% of the dosing interval. RESULTS: The model
      incorporating MM clearance best described the data. Results of our simulation
      revealed that piperacillin/tazobactam dosed at 3-4 g for 30 min every 6-8 h led
      to <90% PTA against MIC values >4 mg/L. More intensive prolonged infusion
      regimens than are commonly used in practice, such as continuous infusions or 3 h
      infusions every 6 h, were needed to maximize the PTA for MICs >= 8 mg/L.
      CONCLUSIONS: Intensive prolonged infusion regimens are the best option to ensure
      optimal exposures against most susceptible isolates in adult patients with CF.

PMID- 23869051
TI  - Isolation of NDM-producing Providencia rettgeri in Brazil.

PMID- 23869052
TI  - Species distribution and antifungal susceptibility of bloodstream fungal isolates
      in paediatric patients in Mexico: a nationwide surveillance study.
AB  - OBJECTIVES: To establish the species distribution and in vitro susceptibilities
      of 358 bloodstream fungal isolates from paediatric patients in Mexico. METHODS:
      Isolates were collected during a 2 year surveillance programme in 14 medical
      centres in 10 Mexican states. A molecular approach was used to determine the
      Candida parapsilosis species complex. In vitro susceptibility to amphotericin B,
      fluconazole, voriconazole, itraconazole, posaconazole, caspofungin, anidulafungin
      and micafungin was determined according to CLSI procedures. Species-specific
      clinical breakpoints for fluconazole, voriconazole and echinocandins were
      applied. RESULTS: Candida spp. accounted for 98.33% of fungaemias, including 127
      Candida albicans isolates, 127 C. parapsilosis complex isolates (121 C.
      parapsilosis sensu stricto, 4 Candida orthopsilosis and 2 Candida metapsilosis
      strains) and 72 Candida tropicalis isolates. C. albicans and C. parapsilosis
      complex were the species predominant in neonates (48 cases each; 41.02%). C.
      parapsilosis complex was also the predominant species in patients 1 month to <2
      years of age (P = 0.007). In contrast, C. albicans was the most frequent species
      in patients aged 2 to <12 years (P = 0.003). Antifungal resistance was rare among
      the subset of isolates. Candida glabrata showed the highest resistance rate to
      amphotericin B (1/9 isolates), fluconazole (1/9 isolates) and itraconazole (2/9
      isolates). CONCLUSIONS: The species distribution differed with the age of the
      patients, with C. albicans and C. parapsilosis complex being the most commonly
      isolated species. C. glabrata showed the highest resistance rate to amphotericin
      B, fluconazole and itraconazole. This is the first study of fungaemia episodes in
      Mexican children.

PMID- 23869053
TI  - Characterization of CXCR4-using HIV-1 during primary infection by ultra-deep
      pyrosequencing.
AB  - OBJECTIVES: R5 viruses have long been thought to account for almost all strains
      present in primary HIV-1 infections (PHIs), but recent studies using sensitive
      phenotypic assays have revealed that 3%-6.4% of subjects also harbour CXCR4-using
      viruses. Phenotypic assays provide only qualitative results: the presence or
      absence of CXCR4-using viruses. We have therefore used ultra-deep pyrosequencing
      (UDS) to determine the frequency of CXCR4-using viruses among HIV-1 quasispecies.
      METHODS: We first screened 200 patients for HIV-1 tropism using a sensitive
      phenotypic assay during PHI and identified 11 infected with an R5X4 dual/mixed
      (D/M) virus population. We then used UDS of the V3 env region with the geno2pheno
      algorithm (false positive rate = 5.75) to identify the HIV-1 quasispecies.
      RESULTS: CXCR4-using viruses were detected in all but 1 of the 11 patients by
      UDS, and accounted for 0.2%-100% of the virus populations. The frequency of CXCR4
      using viruses was <20% in six subjects and 100% in four subjects. Virus
      populations containing 100% CXCR4-using variants during PHI persisted for at
      least 1-2 years after the acute phase. The CCR5 Delta32 heterozygous genotype was
      similarly prevalent in patients infected with D/M (27%) and R5 (15%) viruses.
      CONCLUSIONS: UDS and the phenotype were concordant for determining HIV-1
      coreceptor usage. UDS analysis indicated large differences in the percentage of
      CXCR4-using viruses in the HIV-1 quasispecies during PHI. Further studies should
      examine the impact of the proportion of CXCR4-using viruses on disease prognosis.

PMID- 23869054
TI  - Legislative epidemics: the role of model law in the transnational trend to
      criminalise HIV transmission.
AB  - HIV-related state laws are being created transnationally though the use of
      omnibus model laws. In 2004, the US Agency for International Development (USAID)
      funded the creation of one such guidance text known as the USAID/Action for West
      Africa Region Model Law, or N'Djamena Model Law, which led to the rapid spread of
      HIV/AIDS laws, including the criminalisation of HIV transmission, across much of
      West and Central Africa (2005-2010). In this article, I explicate how an epidemic
      of highly problematic legislation spread across the region as a result of a text
      mediated work process enabled through model laws. I theorise the textual genre of
      model laws arguing that these texts are best understood as 'preoperative
      documents' which, when activated, can lead to swift legislative reform in and
      beyond the field of HIV/AIDS governance. The legislative process being
      investigated was made visible through participant observation, archival research,
      textual analysis and informant interviews with national and international
      stakeholders (n=32). This involved ethnographic research in Canada, the USA,
      Switzerland, Austria, South Africa and Senegal (2010-2011). The untold policy
      processes and narratives explored in this article make evident how the work of
      contesting problematic HIV/AIDS model laws and newly drafted state laws involves
      both creating new texts and contesting the legitimacy and efficacy of others. 

PMID- 23869055
TI  - Inflammatory and procoagulant cytokine levels during pregnancy as predictors of
      adverse obstetrical complications.
AB  - INTRODUCTION: Disturbances in cytokine networks are believed to be associated
      with increased risk of adverse pregnancy complications. METHODS: Plasma samples
      collected from pregnant women with preterm deliveries, high-risk pregnancy
      complications including postpartum hemorrhage, hypertensive disorders, and
      multiple gestations, and normal pregnancies were analyzed at different periods
      throughout gestation and postpartum. Interleukin (IL) 1beta , IL-6, IL-8, IL-10,
      tumor necrosis factor alpha, and antiprotein Z antibody levels were measured by
      enzyme-linked immunosorbent assay. RESULTS: The IL-6 levels in preterm delivery
      patients were elevated during pregnancy with statistically significant
      differences observed at 21 to 32 weeks (P < .01) and 33+ weeks (P < .001). The IL
      10 levels were increased in normal pregnancy at all time points compared to the
      other patient groups (P < .05). The TNF-alpha levels were elevated in the high
      risk pregnancy group versus normal controls (P < .001 at <21 weeks and P < .05 at
      21-32 weeks). CONCLUSION: Analysis of the maternal plasma for elevated IL-6 and
      reduced IL-10 levels may be of value in the early prediction of pregnancy
      complications.

PMID- 23869056
TI  - The Prevalence of Factor V Leiden (G1691A) and Methylenetetrahydrofolate
      Reductase C677T Mutations in Sickle Cell Disease in Western India.
AB  - The prevalence of the Factor V Leiden (FVL; G1691A) mutation and the
      methylenetetrahydrofolate reductase (MTHFR; C677T) mutation was determined in 180
      patients with sickle cell (SS) disease (126 sickle homozygous and 54 sickle beta
      thalassaemia--age 1-47 years) and in 130 healthy controls. The FVL mutation in
      the heterozygous state was present in only 3 patients with SS disease and was
      absent in the controls. Genotyping of MTHFR 677C > T revealed increased frequency
      of the C allele than the T allele in patients as well as in controls. This
      suggests that these genetic markers may not be major risk factors for a
      hypercoagulable state in Indian patients with SS disease.

PMID- 23869057
TI  - Time course of gene expression during mouse skeletal muscle hypertrophy.
AB  - The purpose of this study was to perform a comprehensive transcriptome analysis
      during skeletal muscle hypertrophy to identify signaling pathways that are
      operative throughout the hypertrophic response. Global gene expression patterns
      were determined from microarray results on days 1, 3, 5, 7, 10, and 14 during
      plantaris muscle hypertrophy induced by synergist ablation in adult mice.
      Principal component analysis and the number of differentially expressed genes
      (cutoffs >=2-fold increase or >=50% decrease compared with control muscle)
      revealed three gene expression patterns during overload-induced hypertrophy:
      early (1 day), intermediate (3, 5, and 7 days), and late (10 and 14 days)
      patterns. Based on the robust changes in total RNA content and in the number of
      differentially expressed genes, we focused our attention on the intermediate gene
      expression pattern. Ingenuity Pathway Analysis revealed a downregulation of genes
      encoding components of the branched-chain amino acid degradation pathway during
      hypertrophy. Among these genes, five were predicted by Ingenuity Pathway Analysis
      or previously shown to be regulated by the transcription factor Kruppel-like
      factor-15, which was also downregulated during hypertrophy. Moreover, the
      integrin-linked kinase signaling pathway was activated during hypertrophy, and
      the downregulation of muscle-specific micro-RNA-1 correlated with the
      upregulation of five predicted targets associated with the integrin-linked kinase
      pathway. In conclusion, we identified two novel pathways that may be involved in
      muscle hypertrophy, as well as two upstream regulators (Kruppel-like factor-15
      and micro-RNA-1) that provide targets for future studies investigating the
      importance of these pathways in muscle hypertrophy. 

PMID- 23869059
TI  - Central common drive to antagonistic ankle muscles in relation to short-term
      cocontraction training in nondancers and professional ballet dancers.
AB  - Optimization of cocontraction of antagonistic muscles around the ankle joint has
      been shown to involve plastic changes in spinal and cortical neural circuitries.
      Such changes may explain the ability of elite ballet dancers to maintain a steady
      balance during various ballet postures. Here we investigated whether short-term
      cocontraction training in ballet dancers and nondancers leads to changes in the
      coupling between antagonistic ankle motor units. Eleven ballet dancers and 10
      nondancers were recruited for the study. Prior to training, ballet dancers and
      nondancers showed an equal amount of coherence in the 15- to 35-Hz frequency band
      and short-term synchronization between antagonistic tibialis anterior and soleus
      motor units. The ballet dancers tended to be better at maintaining a stable
      cocontraction of the antagonistic muscles, but this difference was not
      significant (P = 0.09). Following 27 min of cocontraction training, the
      nondancers improved their performance significantly, whereas no significant
      improvement was observed for the ballet dancers. The nondancers showed a
      significant increase in 15- to 35-Hz coherence following the training, whereas
      the ballet dancers did not show a significant change. A group of control subjects
      (n = 4), who performed cocontraction of the antagonistic muscles for an equal
      amount of time, but without any requirement to improve their performance, showed
      no change in coherence. We suggest that improved ability to maintain a stable
      cocontraction around the ankle joint is accompanied by short-term plastic changes
      in the neural drive to the involved muscles, but that such changes are not
      necessary for maintained high-level performance. 

PMID- 23869058
TI  - Changes in neurochemicals within the ventrolateral medullary respiratory column
      in awake goats after carotid body denervation.
AB  - A current and major unanswered question is why the highly sensitive central
      CO2/H(+) chemoreceptors do not prevent hypoventilation-induced hypercapnia
      following carotid body denervation (CBD). Because perturbations involving the
      carotid bodies affect central neuromodulator and/or neurotransmitter levels
      within the respiratory network, we tested the hypothesis that after CBD there is
      an increase in inhibitory and/or a decrease in excitatory neurochemicals within
      the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic
      use were implanted bilaterally in the VMC within or near the pre-Botzinger
      Complex (preBotC) through which mock cerebrospinal fluid (mCSF) was dialyzed.
      Effluent mCSF was collected and analyzed for neurochemical content. The goats
      hypoventilated (peak +22.3 +/- 3.4 mmHg PaCO2) and exhibited a reduced CO2
      chemoreflex (nadir, 34.8 +/- 7.4% of control DeltaVE/DeltaPaCO2) after CBD with
      significant but limited recovery over 30 days post-CBD. After CBD, GABA and
      glycine were above pre-CBD levels (266 +/- 29% and 189 +/- 25% of pre-CBD; P <
      0.05), and glutamine and dopamine were significantly below pre-CBD levels (P <
      0.05). Serotonin, substance P, and epinephrine were variable but not
      significantly (P > 0.05) different from control after CBD. Analyses of brainstem
      tissues collected 30 days after CBD exhibited 1) a midline raphe-specific
      reduction (P < 0.05) in the percentage of tryptophan hydroxylase-expressing
      neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five
      medullary respiratory nuclei. We conclude that after CBD, an increase in
      inhibitory neurotransmitters and a decrease in excitatory neuromodulation within
      the VMC/preBotC likely contribute to the hypoventilation and attenuated
      ventilatory CO2 chemoreflex. 

PMID- 23869060
TI  - Diminished leptin signaling can alter circadian rhythm of metabolic activity and
      feeding.
AB  - Leptin, a hormone mainly produced by fat cells, shows cell-specific effects to
      regulate feeding and metabolic activities. We propose that an important feature
      of metabolic dysregulation resulting in obesity is the loss of the circadian
      rhythm of biopotentials. This was tested in the pan-leptin receptor knockout
      (POKO) mice newly generated in our laboratory. In the POKO mice, leptin no longer
      induced pSTAT-3 signaling after intracerebroventricular injection. Three basic
      phenotypes were observed: the heterozygotes had similar weight and adiposity as
      the wild-type (WT) mice (>60% of the mice); the homozygotes were either fatter
      (~30%), or rarely leaner (<5%) than the WT mice. By early adulthood, the POKO
      mice had higher average body weight and adiposity than their respective same-sex
      WT littermate controls, and this was consistent among different batches. The
      homozygote fat POKO showed significant reduction of midline estimating statistic
      of rhythm of circadian parameters, and shifts of ultradian rhythms. The blunted
      circadian rhythm of these extremely obese POKO mice was also seen in their
      physical inactivity, longer feeding bouts, and higher food intake. The extent of
      obesity correlated with the blunted circadian amplitude, accumulative metabolic
      and locomotor activities, and the severity of hyperphagia. This contrasts with
      the heterozygote POKO mice which showed little obesity and metabolic disturbance,
      and only subtle changes of the circadian rhythm of metabolic activity without
      alterations in feeding behavior. The results provide a novel aspect of leptin
      resistance, almost manifesting as an "all or none" phenomenon. 

PMID- 23869061
TI  - Oral sapropterin augments reflex vasoconstriction in aged human skin through
      noradrenergic mechanisms.
AB  - Reflex vasoconstriction is attenuated in aged skin due to a functional loss of
      adrenergic vasoconstriction. Bioavailability of tetrahydrobiopterin (BH4), an
      essential cofactor for catecholamine synthesis, is reduced with aging. Locally
      administered BH4 increases vasoconstriction through adrenergic mechanisms in aged
      human skin. We hypothesized that oral sapropterin (Kuvan, a pharmaceutical BH4)
      would augment vasoconstriction elicited by whole-body cooling and tyramine
      perfusion in aged skin. Ten healthy subjects (age 75 +/- 2 yr) ingested
      sapropterin (10 mg/kg) or placebo in a randomized, double-blind crossover design.
      Venous blood samples were collected prior to, and 3 h following ingestion. Three
      intradermal microdialysis fibers were placed in the forearm skin for local
      delivery of 1) lactated Ringer, 2) 5 mM BH4, and 3) 5 mM yohimbine + 1 mM
      propranolol (Y+P; to inhibit adrenergic vasoconstriction). Red cell flux was
      measured at each site by laser-Doppler flowmetry (LDF) as reflex vasoconstriction
      was induced by lowering and then clamping whole-body skin temperature (Tsk) using
      a water-perfused suit. Following whole-body cooling, subjects were rewarmed and 1
      mM tyramine was perfused at each site to elicit endogenous norepinephrine release
      from the perivascular nerve terminal. Cutaneous vascular conductance was
      calculated as CVC = LDF/mean arterial pressure and expressed as change from
      baseline (DeltaCVC). Plasma BH4 was elevated 3 h after ingestion of sapropterin
      (43.8 +/- 3 vs. 19.1 +/- 2 pmol/ml; P < 0.001). Sapropterin increased reflex
      vasoconstriction at the Ringer site at Tsk <= 32.5 degrees C (P < 0.05). Local
      BH4 perfusion augmented reflex vasoconstriction at Tsk <= 31.5 degrees C with
      placebo treatment only (P < 0.05). There was no treatment effect on reflex
      vasoconstriction at the BH4-perfused or Y+P-perfused sites. Sapropterin increased
      pharmacologically induced vasoconstriction at the Ringer site (-0.19 +/- 0.03 vs.
      -0.08 +/- 0.02 DeltaCVC; P = 0.01). There was no difference in pharmacologically
      induced vasoconstriction between treatments at the BH4-perfused site (-0.16 +/-
      0.04 vs. -0.14 +/- 0.03 DeltaCVC; P = 0.60) or the Y+P-perfused site (-0.05 +/-
      0.02 vs.-0.06 +/- 0.02 DeltaCVC; P = 0.79). Sapropterin increases both reflex
      (cold-induced) and pharmacologically induced vasoconstriction through adrenergic
      mechanisms and may be a viable intervention to improve reflex vasoconstriction in
      aged humans. 

PMID- 23869063
TI  - Intravenous adenosine activates diffuse nociceptive inhibitory controls in
      humans.
AB  - Experimentally induced pain can be attenuated by concomitant heterotopic
      nociceptive stimuli (counterirritation). Animal data indicate that this stems
      from supraspinal "diffuse noxious inhibitory controls" (DNICs) triggered by C and
      Adelta fibers. In humans, only noxious stimuli induce counterirritation. This
      points at C fibers, but the effects of pharmacologically stimulating C fibers
      have not been studied. Intravenous adenosine activates pulmonary C fibers and
      induces dyspnea. This study tests the hypothesis that putative activation of
      pulmonary C fibers by adenosine would trigger DNICs in humans and induce
      counterirritation. Twelve healthy volunteers were included (with valid results
      available in 9) and studied according to a double-blind, randomized, cross-over
      design (intravenous adenosine, 140 MUg.kg(-1).min(-1), during 5 min vs. placebo).
      We measured ventilatory variables and end-tidal CO2 tension, dyspnea intensity by
      visual analog scale, and the intensity of putative chest pain. The primary
      outcome was the amplitude of the RIII component of the nociceptive flexor reflex
      recorded by biceps femoris electromyogram in response to painful electrical sural
      nerve stimulation (RIII), taken as a substitute for pain perception. Placebo did
      not induce any significant effect. Adenosine induced dyspnea, hyperpnea,
      tachycardia, and significant RIII inhibition (24 +/- 8% at the 4th min, P <
      0.0001). The temporal dynamics of adenosine-induced dyspnea and RIII inhibition
      differed (immediate onset followed by a slow decrease for dyspnea, slower onset
      for RIII inhibition). Intravenous adenosine in normal humans induces
      counterirritation, fueling the notion that C-fiber stimulation trigger DNICs in
      humans. The temporal dissociation between adenosine-induced dyspnea and RIII
      inhibition suggests that C fibers other than pulmonary ones might be involved. 

PMID- 23869062
TI  - Estrogen replacement and skeletal muscle: mechanisms and population health.
AB  - There is a growing body of information supporting the beneficial effects of
      estrogen and estrogen-based hormone therapy (HT) on maintenance and enhancement
      of muscle mass, strength, and connective tissue. These effects are also evident
      in enhanced recovery from muscle atrophy or damage and have significant
      implications particularly for the muscular health of postmenopausal women.
      Evidence suggests that HT will also help maintain or increase muscle mass,
      improve postatrophy muscle recovery, and enhance muscle strength in aged females.
      This is important because this population, in particular, is at risk for a rapid
      onset of frailty. The potential benefits of estrogen and HT relative to skeletal
      muscle function and composition combined with other health-related enhancements
      associated with reduced risk of cardiovascular events, overall mortality, and
      metabolic dysfunction, as well as enhanced cognition and bone health cumulate in
      a strong argument for more widespread and prolonged consideration of HT if
      started proximal to menopausal onset in most women. Earlier reports of increased
      health risks with HT use in postmenopausal women has led to a decline in HT use.
      However, recent reevaluation regarding the health effects of HT indicates a
      general lack of risks and a number of significant health benefits of HT use when
      initiated at the onset of menopause. Although further research is still needed to
      fully delineate its mechanisms of action, the general use of HT by postmenopausal
      women, to enhance muscle mass and strength, as well as overall health, with
      initiation soon after the onset of menopause should be considered. 

PMID- 23869064
TI  - Model-based causal closed-loop approach to the estimate of baroreflex sensitivity
      during propofol anesthesia in patients undergoing coronary artery bypass graft.
AB  - Cardiac baroreflex is a fundamental component of the cardiovascular control. The
      continuous assessment of baroreflex sensitivity (BRS) from spontaneous heart
      period (HP) and systolic arterial pressure (SAP) variations during general
      anesthesia provides relevant information about cardiovascular regulation in
      physiological conditions. Unfortunately, several difficulties including unknown
      HP-SAP causal relations, negligible SAP changes, small BRS values, and
      confounding influences due to mechanical ventilation prevent BRS monitoring from
      HP and SAP variabilities during general anesthesia. We applied a model-based
      causal closed-loop approach aiming at BRS assessment during propofol anesthesia
      in 34 patients undergoing coronary artery bypass graft (CABG) surgery. We found
      the following: 1) traditional time and frequency domain approaches (i.e.,
      baroreflex sequence, cross-correlation, spectral, and transfer function
      techniques) exhibited irremediable methodological limitations preventing the
      assessment of the BRS decrease during propofol anesthesia; 2) Granger causality
      approach proved that the methodological caveats were linked to the decreased
      presence of bidirectional closed-loop HP-SAP interactions and to the increased
      incidence of the HP-SAP uncoupling; 3) our model-based closed-loop approach
      detected the significant BRS decrease during propofol anesthesia as a likely
      result of accounting for the influences of mechanical ventilation and causal HP
      SAP interactions; and 4) the model-based closed-loop approach found also a
      diminished gain of the relation from HP to SAP linked to vasodilatation and
      reduced ventricular contractility during propofol anesthesia. The proposed model
      based causal closed-loop approach is more effective than traditional approaches
      in monitoring cardiovascular control during propofol anesthesia and indicates an
      overall depression of the HP-SAP closed-loop regulation. 

PMID- 23869065
TI  - Nose-only water-pipe smoking effects on airway resistance, inflammation, and
      oxidative stress in mice.
AB  - Water-pipe smoking (WPS) is a common practice in the Middle East and is now
      gaining popularity in Europe and the United States. However, there is a limited
      number of studies on the respiratory effects of WPS. More specifically, the
      underlying pulmonary pathophysiological mechanisms related to WPS exposure are
      not understood. Presently, we assessed the respiratory effects of nose-only
      exposure to mainstream WPS generated by commercially available honey flavored
      "moasel" tobacco. The duration of the session was 30 min/day and 5 days/wk for 1
      mo. Control mice were exposed to air only. Here, we measured in BALB/c mice the
      airway resistance using forced-oscillation technique. Lung inflammation was
      assessed histopathologically and by biochemical analysis of bronchoalveolar
      lavage (BAL) fluid, and oxidative stress was evaluated biochemically by measuring
      lipid peroxidation, reduced glutathione and several antioxidant enzymes.
      Pulmonary inflammation assessment showed an increase in neutrophil and lymphocyte
      numbers. Likewise, airway resistance was significantly increased in the WPS group
      compared with controls. Tumor necrosis factor alpha and interleukin 6
      concentrations were significantly increased in BAL fluid. Lipid peroxidation in
      lung tissue was significantly increased whereas the level and activity of
      antioxidants including reduced glutathione, glutathione S transferase, and
      superoxide dismutase were all significantly decreased following WPS exposure,
      indicating the occurrence of oxidative stress. Moreover, carboxyhemoglobin levels
      were significantly increased in the WPS group. We conclude that 1-mo nose-only
      exposure to WPS significantly increased airway resistance, inflammation, and
      oxidative stress. Our results provide a mechanistic explanation for the limited
      clinical studies that reported the detrimental respiratory effects of WPS. 

PMID- 23869066
TI  - Multiple inert gas elimination technique by micropore membrane inlet mass
      spectrometry--a comparison with reference gas chromatography.
AB  - The mismatching of alveolar ventilation and perfusion (VA/Q) is the major
      determinant of impaired gas exchange. The gold standard for measuring VA/Q
      distributions is based on measurements of the elimination and retention of
      infused inert gases. Conventional multiple inert gas elimination technique
      (MIGET) uses gas chromatography (GC) to measure the inert gas partial pressures,
      which requires tonometry of blood samples with a gas that can then be injected
      into the chromatograph. The method is laborious and requires meticulous care. A
      new technique based on micropore membrane inlet mass spectrometry (MMIMS)
      facilitates the handling of blood and gas samples and provides nearly real-time
      analysis. In this study we compared MIGET by GC and MMIMS in 10 piglets: 1) 3
      with healthy lungs; 2) 4 with oleic acid injury; and 3) 3 with isolated left
      lower lobe ventilation. The different protocols ensured a large range of normal
      and abnormal VA/Q distributions. Eight inert gases (SF6, krypton, ethane,
      cyclopropane, desflurane, enflurane, diethyl ether, and acetone) were infused;
      six of these gases were measured with MMIMS, and six were measured with GC. We
      found close agreement of retention and excretion of the gases and the constructed
      VA/Q distributions between GC and MMIMS, and predicted PaO2 from both methods
      compared well with measured PaO2. VA/Q by GC produced more widely dispersed modes
      than MMIMS, explained in part by differences in the algorithms used to calculate
      VA/Q distributions. In conclusion, MMIMS enables faster measurement of VA/Q, is
      less demanding than GC, and produces comparable results. 

PMID- 23869067
TI  - Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude.
AB  - Tibetans have been reported to present with a unique phenotypic adaptation to
      high altitude characterized by higher resting ventilation and arterial oxygen
      saturation, no excessive polycythemia, and lower pulmonary arterial pressures
      (Ppa) compared with other high-altitude populations. How this affects exercise
      capacity is not exactly known. We measured aerobic exercise capacity during an
      incremental cardiopulmonary exercise test, lung diffusing capacity for carbon
      monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and
      cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in
      13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In
      Sherpas vs. lowlanders, arterial oxygen saturation was 86 +/- 1 vs. 83 +/- 2%
      (mean +/- SE; P = nonsignificant), mPpa at rest 19 +/- 1 vs. 23 +/- 1 mmHg (P <
      0.05), DL(CO) corrected for hemoglobin 61 +/- 4 vs. 37 +/- 2 ml . min(-1) . mmHg(
      1) (P < 0.001), DL(NO) 226 +/- 18 vs. 153 +/- 9 ml . min(-1) . mmHg(-1) (P <
      0.001), maximum oxygen uptake 32 +/- 3 vs. 28 +/- 1 ml . kg(-1) . min(-1) (P =
      nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic
      threshold 40 +/- 2 vs. 48 +/- 2 (P < 0.001). Maximum oxygen uptake was correlated
      directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships
      in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared
      with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but
      with less pronounced pulmonary hypertension, lower ventilatory responses, and
      higher lung diffusing capacity.

PMID- 23869069
TI  - Rapid and complete recovery in ventilator-induced diaphragm weakness--problem
      solved?

PMID- 23869068
TI  - NSAID therapy effects on healing of bone, tendon, and the enthesis.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment
      of skeletal injuries. The ability of NSAIDs to reduce pain and inflammation is
      well-established. However, the effects of NSAID therapy on healing of skeletal
      injuries is less defined. NSAIDs inhibit cyclooxygenase activity to reduce
      synthesis of prostaglandins, which are proinflammatory, lipid-signaling
      molecules. Inhibition of cyclooxygenase activity can impact many physiological
      processes. The effects of NSAID therapy on healing of bone, tendon, and the
      tendon-to-bone junction (enthesis) have been studied in animal and cell culture
      models, but human studies are few. Use of different NSAIDs with different
      pharmacological properties, differences in dosing regimens, and differences in
      study models and outcome measures have complicated comparisons between studies.
      In this review, we summarize the mechanisms by which bone, tendon, and enthesis
      healing occurs, and describe the effects of NSAID therapy on each of these
      processes. Determining the impact of NSAID therapy on healing of skeletal tissues
      will enable clinicians to appropriately manage the patient's condition and
      improve healing outcomes. 

PMID- 23869070
TI  - Normal pulmonary gas exchange efficiency and absence of exercise-induced arterial
      hypoxemia in adults with bronchopulmonary dysplasia.
AB  - Cardiopulmonary function is reduced in adults born very preterm, but it is
      unknown if this results in reduced pulmonary gas exchange efficiency during
      exercise and, consequently, leads to reduced aerobic capacity in subjects with
      and without bronchopulmonary dysplasia (BPD). We hypothesized that an excessively
      large alveolar to arterial oxygen difference (AaDO2) and resulting exercise
      induced arterial hypoxemia (EIAH) would contribute to reduced aerobic fitness in
      adults born very preterm with and without BPD. Measurements of pulmonary
      function, lung volumes and diffusion capacity for carbon monoxide (DLco) were
      made at rest. Measurements of maximal oxygen consumption, peak workload,
      temperature- and tonometry-corrected arterial blood gases, and direct measure of
      hemoglobin saturation with oxygen (SaO2) were made preexercise and during cycle
      ergometer exercise in ex-preterm subjects <=32-wk gestational age, with BPD (n =
      12), without BPD (PRE; n = 12), and full term controls (CONT; n = 12) breathing
      room air. Both BPD and PRE had reduced pulmonary function and reduced DLco
      compared with CONT. The AaDO2 was not significantly different between groups, and
      there was no evidence of EIAH (SaO2 < 95% and/or AaDO2 >= 40 Torr) in any subject
      group preexercise or at any workload. Arterial O2 content was not significantly
      different between the groups preexercise or during exercise. However, peak power
      output was decreased in BPD and PRE subjects compared with CONT. We conclude that
      EIAH in adult subjects born very preterm with and without BPD does not likely
      contribute to the reduction in aerobic exercise capacity observed in these
      subjects. 

PMID- 23869071
TI  - 'Lingering' opiate deaths? Concentration of opiates in medulla and femoral blood.
AB  - 'Lingering death' cases occur when the circumstances of death indicate an opiate
      overdose, but measured opiate blood levels are only in the therapeutic range;
      death results from cardiac and respiratory depression. This study examined the
      relative concentration of opiates in femoral blood and in the medulla oblongata
      (sites for cardiac and respiratory control) from 41 cases to determine whether a
      difference in opiate concentration might explain lingering deaths. Opiates from
      blood and medulla were analyzed using GC-EI-MS in selective ion monitoring mode.
      Results were correlated with gross and microscopic findings of the lungs and with
      cause and manner of death. Opiate concentrations for morphine, codeine and 6
      acetylmorphine (6-AM) were higher in the medulla than in blood. The brain: blood
      ratio for the analytes demonstrated an increasing ratio from morphine, to
      codeine, to 6-AM (1.42, 2.48 and 4.86), which corresponds to the relative
      lipophilicity of these analytes. The average right and left lung weights were 762
      and 668 g, respectively. Histologic examination showed edema, and/or polarizable
      microemboli, acute bronchopneumonia and acute bronchitis. The preferential
      distribution of opiates to medulla suggests that lingering opiate deaths may be
      explained, at least in part, because of higher relative concentrations of drug in
      brain, compared with femoral blood. 

PMID- 23869072
TI  - Modified antibody in fetal alloimmunization.
AB  - In this issue of Blood, Ghevaert et al propose to develop a therapeutic antibody
      for fetal and neonatal alloimmune thrombocytopenia (FNAIT) that would block the
      actual antibody in sensitized mothers from binding and therefore prevent, or at
      least ameliorate, fetal and neonatal thrombocytopenia in fetuses who would
      otherwise be affected.1 The goal of the group is to engineer an antibody reagent
      that would on the one hand not engage conventional activating Fc receptors and on
      the other hand interact normally with FcRn, allowing transplacental passage.

PMID- 23869073
TI  - Trick to treat: tricking the thymus to treat cancer.
AB  - In this issue of Blood, Schmitt et al address the biology and safety of T cells
      engineered to express T-cell receptor (TCR) variants endowed with enhanced
      affinity for tumor-associated antigens.

PMID- 23869074
TI  - Scouting out the neighborhood in AIDS-related lymphoma.
AB  - In this issue of Blood, Liapis et al investigate the characteristics of the tumor
      microenvironment as well as the role of viral components in AIDS-related diffuse
      large B-cell lymphoma (AR-DLBCL) and compare these findings with sporadic cases
      of DLBCL.

PMID- 23869075
TI  - A platelet cover-up.
AB  - In this issue of Blood, Bakchoul et al explore a novel approach to the treatment
      of neonatal alloimmune thrombocytopenia (NAIT) in utero: shielding fetal
      platelets from maternal alloantibodies.

PMID- 23869076
TI  - Mononuclear phagocytes and marker modulation: when CD16 disappears, CD38 takes
      the stage.

PMID- 23869077
TI  - Non-Hodgkin lymphoma in familial amyloid polyneuropathy patients in Sweden.

PMID- 23869078
TI  - The microenvironment of AIDS-related diffuse large B-cell lymphoma provides
      insight into the pathophysiology and indicates possible therapeutic strategies.

PMID- 23869079
TI  - No familial aggregation in chronic myeloid leukemia.

PMID- 23869080
TI  - A missense mutation in ANKRD26 segregates with thrombocytopenia.

PMID- 23869081
TI  - Localized edema with sclerodermatous evolution: a possible form of skin chronic
      graft-versus-host disease associated with endothelial activation.

PMID- 23869083
TI  - Targeting apoptosis to induce stable mixed hematopoietic chimerism and long-term
      allograft survival without myelosuppressive conditioning in mice.
AB  - Induction of mixed hematopoietic chimerism results in donor-specific
      immunological tolerance by apoptosis-mediated deletion of donor-reactive
      lymphocytes. A broad clinical application of this approach is currently hampered
      by limited predictability and toxicity of the available conditioning protocols.
      We developed a new therapeutic approach to induce mixed chimerism and tolerance
      by a direct pharmacological modulation of the intrinsic apoptosis pathway in
      peripheral T cells. The proapoptotic small-molecule Bcl-2 inhibitor ABT-737
      promoted mixed chimerism induction and reversed the antitolerogenic effect of
      calcineurin inhibitors by boosting the critical role of the proapoptotic Bcl-2
      factor Bim. A short conditioning protocol with ABT-737 in combination with
      costimulation blockade and low-dose cyclosporine A resulted in a complete
      deletion of peripheral donor-reactive lymphocytes and was sufficient to induce
      mixed chimerism and robust systemic tolerance across full major
      histocompatibility complex barriers, without myelosuppression and by using
      moderate doses of bone marrow cells. Thus, immunological tolerance can be
      achieved by direct modulation of the intrinsic apoptosis pathway in peripheral
      lymphocytes-a new approach to translate immunological tolerance into clinically
      applicable protocols. 

PMID- 23869084
TI  - Long-term remission of T-cell large granular lymphocyte leukemia associated with
      rheumatoid arthritis after rituximab therapy.
AB  - T-cell large granular lymphocyte leukemia (LGLL) is a rare clonal disease often
      associated with rheumatoid arthritis (RA) and manifests chiefly as neutropenia
      and recurrent infections. Immunosuppressive agents are the mainstay of treatment,
      but long-term remissions are rare. We report 2 cases of LGLL in patients with RA
      successfully treated with rituximab, a monoclonal antibody specific of B cells
      and approved for treating RA. The first patient experienced a complete LGLL
      remission that was sustained during the 8-year follow-up after the first
      rituximab infusion. In the second patient, rituximab therapy was followed by
      immediate neutropenia recovery and then by marked shrinkage of the LGLL clone 1
      year later. The paradoxical efficacy of this specific anti-B-cell drug on a
      monoclonal T-cell disease suggests that some cases of LGLL may be reactive
      manifestations of chronic autoantigen stimulation rather than true malignancies. 

PMID- 23869085
TI  - Differences in gene expression and cytokine levels between newly diagnosed and
      chronic pediatric ITP.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disease where platelets are
      destroyed prematurely. In the majority of children the disease resolves, but in
      some it becomes chronic. To investigate whether these 2 phases of the disease are
      molecularly similar or separate entities we performed DNA microarray analysis
      (GEO accession number: GSE46922) of T-cells from newly diagnosed children and
      children with chronic ITP. We found complete separation of the gene expression
      profiles between the 2 phases of the disease. Furthermore, the gene expression
      levels of several cytokines differed between the 2 phases of the disease. This
      was also reflected in plasma with increased levels of interleukin (IL)-16 and TNF
      related weak inducer of apoptosis and lower levels of IL-4 in newly diagnosed
      compared with chronic ITP. Thus, our data indicate that chronic ITP in childhood
      is a separate disease entity, dissimilar in many aspects to the newly diagnosed
      phase.

PMID- 23869086
TI  - Increased circulating levels of neurotrophins and elevated expression of their
      high-affinity receptors on skin and gut mast cells in mastocytosis.
AB  - Mastocytosis is a rare heterogeneous disease characterized by increase of mast
      cells (MCs) in different organs. Neurotrophins (NTs) have been shown to promote
      differentiation and survival of MCs, which in turn represent a major source of
      NTs. Thus, a contribution of NTs to mastocytosis seems highly conceivable but has
      not yet been investigated. We could demonstrate expression of high-affinity NT
      receptors tropomyosin-related kinase A (TrkA) for nerve growth factor (NGF)-beta,
      TrkB for brain-derived neurotrophic factor, and NT-4 and TrkC for NT-3 on skin
      MCs; and of TrkA and TrkC on intestinal MCs of patients with mastocytosis.
      Moreover, increased expression of NGF-beta; NT-3; TrkA, TrkB, and TrkC; and
      isoforms truncated TrkB-T1 and truncated TrkC were observed on skin MCs. Patients
      with mastocytosis featured elevated serum levels of NGF, NT-3, and NT-4. Levels
      of NGF-beta and NT-4 correlated with tryptase levels, suggesting a link between
      MC load and blood levels of NGF and NT-4. Migration of CD117+ progenitor cells
      from the blood was enhanced toward NGF-beta gradient in both mastocytosis and
      controls. Together with enhanced NT levels, the elevated expression of modified
      Trk receptors on skin and gut MCs might contribute to the pathophysiology of
      mastocytosis in autocrine and paracrine loops.

PMID- 23869087
TI  - Staphylococcus aureus recognition by hematopoietic stem and progenitor cells via
      TLR2/MyD88/PGE2 stimulates granulopoiesis in wounds.
AB  - During bacterial infection, hematopoietic stem and progenitor cells (HSPCs)
      differentiate into polymorphonuclear leukocytes (PMNs) in the bone marrow. We
      reported that HSPCs recruited to Staphylococcus aureus-infected skin wounds in
      mice undergo granulopoiesis, whereas other authors have demonstrated their
      differentiation in vitro after Toll-like receptor 2 (TLR2)/MyD88 stimulation.
      Here, we examined this pathway in HSPC trafficking and granulopoiesis within S
      aureus-infected wounds. Lineage- HSPCs from TLR2- or MyD88-deficient mice
      injected into infected wounds of wild-type (WT) mice exhibited impaired
      granulopoiesis. However, HSPCs from WT mice produced similar numbers of PMNs
      whether transferred into wounds of TLR2-, MyD88-deficient, or WT mice.
      Prostaglandin E2 (PGE2), which stimulates HSPC survival and proliferation, was
      produced by HSPCs after TLR2 stimulation, suggesting that TLR2/MyD88 activation
      promotes granulopoiesis in part by production and autocrine activity of PGE2.
      Pretreatment of TLR2- or MyD88-deficient HSPCs with PGE2 rescued granulocytic
      differentiation in vivo. Finally, we demonstrate that bone marrow-derived lin
      /Sca-1+/c-kit+ cells produced PGE2 and underwent granulopoiesis after TLR2
      stimulation. lin-/Sca-1+/c-kit+ cells deficient in TLR2 or MyD88 produced PMNs
      after PGE2 treatment when transferred into uninfected wounds. We conclude that
      granulopoiesis in S aureus-infected wounds is induced by TLR2/MyD88 activation of
      HSPCs through a mechanism that involves autocrine production and activity of
      PGE2.

PMID- 23869088
TI  - IkappaB-zeta controls the constitutive NF-kappaB target gene network and survival
      of ABC DLBCL.
AB  - Constitutive activation of the nuclear factor-kappa B (NF-kappaB) pathway is a
      hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell
      lymphoma (DLBCL). Recurrent mutations of NF-kappaB regulators that cause
      constitutive activity of this oncogenic pathway have been identified. However, it
      remains unclear how specific target genes are regulated. We identified the
      atypical nuclear IkappaB protein IkappaB-zeta to be upregulated in ABC compared
      with germinal center B-cell-like (GCB) DLBCL primary patient samples. Knockdown
      of IkappaB-zeta by RNA interference was toxic to ABC but not to GCB DLBCL cell
      lines. Gene expression profiling after IkappaB-zeta knockdown demonstrated a
      significant downregulation of a large number of known NF-kappaB target genes,
      indicating an essential role of IkappaB-zeta in regulating a specific set of NF
      kappaB target genes. To further investigate how IkappaB-zeta mediates NF-kappaB
      activity, we performed immunoprecipitations and detected a physical interaction
      of IkappaB-zeta with both p50 and p52 NF-kappaB subunits, indicating that IkappaB
      zeta interacts with components of both the canonical and the noncanonical NF
      kappaB pathway in ABC DLBCL. Collectively, our data demonstrate that IkappaB-zeta
      is essential for nuclear NF-kappaB activity in ABC DLBCL, and thus might
      represent a promising molecular target for future therapies. 

PMID- 23869089
TI  - Crystal structure of the prothrombinase complex from the venom of Pseudonaja
      textilis.
AB  - The prothrombinase complex, composed of the protease factor (f)Xa and cofactor
      fVa, efficiently converts prothrombin to thrombin by specific sequential cleavage
      at 2 sites. How the complex assembles and its mechanism of prothrombin processing
      are of central importance to human health and disease, because insufficient
      thrombin generation is the root cause of hemophilia, and excessive thrombin
      production results in thrombosis. Efforts to determine the crystal structure of
      the prothrombinase complex have been thwarted by the dependence of complex
      formation on phospholipid membrane association. Pseutarin C is an intrinsically
      stable prothrombinase complex preassembled in the venom gland of the Australian
      Eastern Brown Snake (Pseudonaja textilis). Here we report the crystal structures
      of the fX-fV complex and of activated fXa from P textilis venom and the derived
      model of active pseutarin C. Structural analysis supports a single substrate
      binding channel on fVa, to which prothrombin and the intermediate meizothrombin
      bind in 2 different orientations, providing insight into the architecture and
      mechanism of the prothrombinase complex-the molecular engine of blood
      coagulation. 

PMID- 23869091
TI  - Mortality rates after emergency surgery vary widely between hospitals, study
      shows.

PMID- 23869090
TI  - Association of plasma uric acid with ischaemic heart disease and blood pressure:
      mendelian randomisation analysis of two large cohorts.
AB  - OBJECTIVES: To assess the associations between both uric acid levels and
      hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore
      the potentially confounding role of body mass index. DESIGN: Mendelian
      randomisation analysis, using variation at specific genes (SLC2A9 (rs7442295) as
      an instrument for uric acid; and FTO (rs9939609), MC4R (rs17782313), and TMEM18
      (rs6548238) for body mass index). SETTING: Two large, prospective cohort studies
      in Denmark. PARTICIPANTS: We measured levels of uric acid and related covariables
      in 58,072 participants from the Copenhagen General Population Study and 10,602
      from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic
      heart disease, respectively. MAIN OUTCOME: Blood pressure and prospectively
      assessed ischaemic heart disease. RESULTS: Estimates confirmed known
      observational associations between plasma uric acid and hyperuricaemia with risk
      of ischaemic heart disease and diastolic and systolic blood pressure. However,
      when using genotypic instruments for uric acid and hyperuricaemia, we saw no
      evidence for causal associations between uric acid, ischaemic heart disease, and
      blood pressure. We used genetic instruments to investigate body mass index as a
      potentially confounding factor in observational associations, and saw a causal
      effect on uric acid levels. Every four unit increase of body mass index saw a
      rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an
      increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%). CONCLUSION: By
      contrast with observational findings, there is no strong evidence for causal
      associations between uric acid and ischaemic heart disease or blood pressure.
      However, evidence supports a causal effect between body mass index and uric acid
      level and hyperuricaemia. This finding strongly suggests body mass index as a
      confounder in observational associations, and suggests a role for elevated body
      mass index or obesity in the development of uric acid related conditions.

PMID- 23869092
TI  - Rather than emulate Ofsted's culture of fear, the UK care regulator must engage
      clinicians to improve standards.

PMID- 23869093
TI  - GPs must be encouraged to test out new approaches to primary care, report says.

PMID- 23869094
TI  - India must respect intellectual property rights, report says.

PMID- 23869095
TI  - Government drops plans for minimum alcohol pricing in England and Wales.

PMID- 23869097
TI  - Charity launches L14m UK-wide lung cancer research initiative.

PMID- 23869098
TI  - Report sets out plan for tackling urgent and emergency care pressures.

PMID- 23869099
TI  - CQC sets out new inspection regime for hospitals in England.

PMID- 23869100
TI  - The epidemiology of malpractice claims in primary care: a systematic review.
AB  - OBJECTIVES: The aim of this systematic review was to examine the epidemiology of
      malpractice claims in primary care. DESIGN: A computerised systematic literature
      search was conducted. Studies were included if they reported original data (>=10
      cases) pertinent to malpractice claims, were based in primary care and were
      published in the English language. Data were synthesised using a narrative
      approach. SETTING: Primary care. PARTICIPANTS: Malpractice claimants. PRIMARY
      OUTCOME: Malpractice claim (defined as a written demand for compensation for
      medical injury). We recorded: medical misadventure cited in claims,
      missed/delayed diagnoses cited in claims, outcome of claims, prevalence of claims
      and compensation awarded to claimants. RESULTS: Of the 7152 articles retrieved by
      electronic search, a total of 34 studies met the inclusion criteria and were
      included in the narrative analysis. Twenty-eight studies presented data from
      medical indemnity malpractice claims databases and six studies presented survey
      data. Fifteen studies were based in the USA, nine in the UK, seven in Australia,
      one in Canada and two in France. The commonest medical misadventure resulting in
      claims was failure to or delay in diagnosis, which represented 26-63% of all
      claims across included studies. Common missed or delayed diagnoses included
      cancer and myocardial infarction in adults and meningitis in children. Medication
      error represented the second commonest domain representing 5.6-20% of all claims
      across included studies. The prevalence of malpractice claims in primary care
      varied across countries. In the USA and Australia when compared with other
      clinical disciplines, general practice ranked in the top five specialties
      accounting for the most claims, representing 7.6-20% of all claims. However, the
      majority of claims were successfully defended. CONCLUSIONS: This review of
      malpractice claims in primary care highlights diagnosis and medication error as
      areas to be prioritised in developing educational strategies and risk management
      systems.

PMID- 23869101
TI  - Estimates of restrictive ventilatory defect in the mining industry.
      Considerations for epidemiological investigations: a cross-sectional study.
AB  - OBJECTIVES: (1) To assess the impact of American Thoracic Society and European
      Respiratory Society (ATS/ERS) 'acceptability' and 'usability' criteria for
      spirometry on the estimates of restrictive ventilatory defect in a population of
      taconite miners. (2) To compare estimates of restrictive ventilatory defect with
      three different pulmonary function tests (spirometry, alveolar volume (VA) and
      diffusing capacity (DL,CO)). (3) To assess the role of population characteristics
      on these estimates. DESIGN: Cross-sectional study. SETTING: Current and former
      workers in six current taconite mining operations of northeastern Minnesota were
      surveyed. PARTICIPANTS: We attempted to enrol 3313 participants. Of these, 1353
      responded while 1188 current and former workers fully participated in the survey
      and 1084 performed complete pulmonary function testing and were assessed. PRIMARY
      AND SECONDARY OUTCOME MEASURES: We applied ATS/ERS acceptability criteria for all
      tests and categorised participants into groups according to whether they fully
      met, partially met or did not meet acceptability criteria for spirometry.
      Obstruction and restriction were defined utilising the lower limit of normal for
      all tests. When using VA, restriction was identified after excluding obstruction.
      RESULTS: Only 519 (47.9%) tests fully met ATS/ERS spirometry acceptability
      criteria. Within this group, 5% had obstruction and 6%, restriction on
      spirometry. In contrast, among all participants (N=1084), 16.8% had obstruction,
      while 4.5% had restriction. VA showed similar results in all groups after
      obstruction was excluded. Impaired gas transfer (reduced DL,CO) was identified in
      less than 50% of restriction identified by either spirometry or VA. Body mass
      index (BMI) was significantly related to spirometric restriction in all groups.
      CONCLUSIONS: Population estimates of restriction using spirometry or VA varied by
      spirometric acceptability criteria. Other factors identified as important
      considerations in the estimation of restrictive ventilatory defect included
      increased BMI and gas transfer impairment in a relatively smaller proportion of
      those with spirometric restriction. These insights are important when
      interpreting population-based physiological data in occupational settings.

PMID- 23869103
TI  - Physiological variables associated with the development of acute mountain
      sickness at the South Pole.
AB  - Exposure to altitudes >2500 m can result in acute mountain sickness (AMS), a mild
      and usually self-limiting condition. Research has attempted to identify factors
      associated with developing AMS without controlling important factors related to
      the ascent or collecting a comprehensive set of variables. OBJECTIVES: The
      Antarctic Study of Altitude Physiology (ASAP) investigated variables associated
      with the development of AMS in adults experiencing rapid passive transport to
      altitude by airplane. DESIGN: Our prospective observational trial collected data,
      including personal history, anthropometrics, vital signs, blood samples and
      pulmonary function, at sea level and at altitude. Statistical analysis utilised
      independent sample t tests to investigate between-group differences (p<0.05) and
      a forward, step-wise binary logisitic regression analysis was performed.
      PARTICIPANTS: Of 248 eligible ASAP participants, those who did not use
      acetazolamide (N=98) were included in the present analysis. PRIMARY OUTCOME
      MEASURES: The diagnosis of AMS using the Lake Louise Symptom Score. RESULTS:
      Analysis of participants not using acetazolamide (n=90) found 30 participants
      developed AMS and 60 participants did not. Estimated plasma volume decreased
      significantly at altitude (p=0.025) in the AMS group as compared with the No AMS
      group while body weight did not change (p=0.125). Serum sodium (p=0.045) and low
      density lipoprotein (LDL) (p=0.049) levels were higher in the No AMS group. A
      logistic regression analysis emphasised the contributions of LDL and eosinophil
      levels in the development of AMS. CONCLUSIONS: These results suggest that the
      body water regulation and inflammation are key factors in AMS development when
      all other factors such as the level of physical exertion during ascent, the rate
      and magnitude of ascent and the use of acetazolamide are controlled.

PMID- 23869102
TI  - Quality indicators of clinical cancer care (QC3) in colorectal cancer.
AB  - OBJECTIVES: Assessing the quality of cancer care (QoCC) has become increasingly
      important to providers, regulators and purchasers of care worldwide. The aim of
      this study was to develop evidence-based quality indicators (QIs) for colorectal
      cancer (CRC) to be applied in a population-based setting. DESIGN: A comprehensive
      evidence-based literature search was performed to identify the initial list of
      QIs, which were then selected and developed using a two-step-modified Delphi
      process involving two multidisciplinary expert panels with expertise in CRC care,
      quality of care and epidemiology. SETTING: The QIs of the clinical cancer care
      (QC3) population-based project, which involves all the public and private
      hospitals and clinics present on the territory of Canton Ticino (South
      Switzerland). PARTICIPANTS: Ticino Cancer Registry, The Colorectal Cancer Working
      Group (CRC-WG) and the external academic Advisory Board (AB). MAIN OUTCOME
      MEASURES: Set of QIs which encompass the whole diagnostic-treatment process of
      CRC. RESULTS: Of the 149 QIs that emerged from 181 sources of literature, 104
      were selected during the in-person meeting of CRC-WG. During the Delphi process,
      CRC-WG shortened the list to 89 QI. AB finally validated 27 QIs according to the
      phase of care: diagnosis (N=6), pathology (N=3), treatment (N=16) and outcome
      (N=2). CONCLUSIONS: Using the validated Delphi methodology, including a
      literature review of the evidence and integration of expert opinions from local
      clinicians and international experts, we were able to develop a list of QIs to
      assess QoCC for CRC. This will hopefully guarantee feasibility of data retrieval,
      as well as acceptance and translation of QIs into the daily clinical practice to
      improve QoCC. Moreover, evidence-based selected QIs allow one to assess immediate
      changes and improvements in the diagnostic-therapeutic process that could be
      translated into a short-term benefit for patients with a possible gain both in
      overall and disease-free survival.

PMID- 23869104
TI  - Determinants of workplace injury among Thai Cohort Study participants.
AB  - OBJECTIVES: To explore individual determinants of workplace injury among Thai
      workers. DESIGN: Cross-sectional analysis of a large national cohort. SETTING:
      Thailand. PARTICIPANTS: Thai Cohort Study participants who responded to the 2009
      follow-up survey were included if they reported doing paid work or being self
      employed (n=51 751). OUTCOME MEASURES: Self-reported injury incidence over the
      past 12 months was calculated. Multivariate logistic regression models were used
      to test associations between individual determinants and self-reported workplace
      injury. RESULTS: Workplace injuries were reported by 1317 study participants
      (2.5%); the incidence was 34 (95% CI 32 to 36)/1000 worker-years for men, and 18
      (17-20) for women. Among men working >=41 h and earning <10 000 Baht, the injury
      rate was four times higher compared with men working <11 h and earning >=20 001
      Baht; differences in injury rates were less pronounced in women. Multivariate
      modelling showed that working >=49 h/week (23%) and working for <=10 000
      Bath/month (37%) were associated with workplace injury. The increase in injury
      risk with increased working hours did not exceed the risk expected from increased
      exposure. CONCLUSIONS: Reductions in occupational injury rates could be achieved
      by limiting working hours to 48/week. Particularly for Thai low wage earners and
      those with longer workdays, there is a need for effective injury preventive
      programmes.

PMID- 23869105
TI  - Accuracy of evidence-based criteria for identifying an incident hip fracture in
      the absence of the date of injury: a retrospective database study.
AB  - OBJECTIVES: Hospital discharge data (HDD) in many health systems do not capture
      the date of injury (DOI); the absence of this date hinders researchers' ability
      to distinguish repeat from incident injury admissions. Various approaches using
      somewhat arbitrary criteria have been explored to increase the accuracy of
      incident injury identification. However, these approaches have not been validated
      against a data source which contains DOI. The aim of this study was to determine
      the accuracy of evidence-based criteria for identifying fall-related incident hip
      fractures in the absence of DOI using HDD containing DOI as the reference
      standard. DESIGN: Retrospective database study. SETTING: New Zealand.
      PARTICIPANTS: 8761 patients aged 65+ years admitted for fall-related hip fracture
      between 1 July 2005 and 30 June 2008, inclusive. OUTCOME MEASURES: We defined
      person-identifying HDD containing DOI as the reference standard and calculated
      measures of the accuracy of evidence-based criteria for identifying fall-related
      incident hip fractures from HDD not containing DOI. The criteria were principal
      diagnosis of hip fracture, mechanism of injury indicating a fall, admission type
      emergency, admission source other than a transfer and presence of hip operation
      code(s). For a subsequent fall-related hip fracture, additional criteria were
      time between successive hip fractures >=120 days, and all external cause-of
      injury codes being different to those for the previous hip fracture. RESULTS: The
      sensitivity and specificity of the criteria for identifying fall-related incident
      hip fractures from data not containing DOI were 96.7% and 99.3%, respectively,
      compared with the reference standard. The application of these criteria resulted
      in a slight underestimation of the percentage of patients with multiple hip
      fractures. CONCLUSIONS: Although it is preferable to have DOI; this study
      demonstrates that evidence-based criteria can be used to reliably identify fall
      related incident hip fractures from the person-identifying HDD when DOI is
      unavailable.

PMID- 23869107
TI  - Efficacy of butylscopolamine for the treatment of catheter-related bladder
      discomfort: a prospective, randomized, placebo-controlled, double-blind study.
AB  - BACKGROUND: Catheter-related bladder discomfort (CRBD) secondary to
      intraoperative catheterization of urinary bladder is one of the most distressing
      symptoms during recovery from anaesthesia. Butylscopolamine, a peripheral
      antimuscarinic agent, is effective for relieving the pain, which is because of
      smooth muscle contraction. The aim of this study was to assess the efficacy and
      safety profiles of butylscopolamine in treating CRBD after urological surgeries.
      METHODS: Adult male patients undergoing urological surgery requiring urinary
      bladder catheterization intraoperatively were enrolled. Induction and maintenance
      of anaesthesia were standardized. Patients were randomized into two groups after
      complaining of CRBD in the post-anaesthesia care unit. The control group (n=29)
      received normal saline and the butylscopolamine group (n=28) was administered
      butylscopolamine 20 mg i.v. The severity of CRBD, postoperative pain, and adverse
      effects were assessed at baseline, 20 min, 1, 2, and 6 h after administration of
      the study drug. RESULTS: The severity of CRBD observed in the butylscopolamine
      group was significantly lower than that of the control group at 1, 2, and 6 h
      after administration of the study drug [59 (12), 50 (16), 40 (21) in the control
      group vs 41 (22), 32 (25), 23 (18) in the butylscopolamine group, P<0.01]. Rescue
      analgesics were required less in the butylscopolamine group than in the control
      group (P=0.001). Adverse events were comparable between the two groups.
      CONCLUSION: Butylscopolamine 20 mg administered i.v. after complaining CRBD
      during recovery reduced both the severity of CRBD and the need for rescue
      analgesics without adverse effects in patients undergoing urologic surgeries.

PMID- 23869108
TI  - Comparison of haemoglobin measurement methods in the operating theatre.
AB  - BACKGROUND: Various methods of haemoglobin (Hb) measurement are available to
      guide transfusion including several methods that allow for measurement at the
      bedside. This study directly compared their absolute and trend accuracy compared
      with values from the central lab (reference method). METHODS: Adult patients
      undergoing surgery with expected blood loss wore a rainbow ReSposable sensor
      connected to a Radical-7 Pulse CO-Oximeter (SpHb). Arterial samples were analysed
      with a haematology analyser (HbLab), a satellite CO-Oximeter (HbSat), and a point
      of-care haemoglobinometer (HemoCue; HcueArt). Concomitantly, ear capillary blood
      was tested using the same haemoglobinometer (HcueCap). Absolute accuracy and the
      clinical significance of error were assessed with Bland-Altman plots and three
      zone error grids. Trend analysis was performed using a modified polar plot,
      testing both directionality and magnitude of Hb changes compared with the
      reference. RESULTS: Two hundred and nineteen measurements from 53 patients with
      HbLab ranging between 6.8 and 16.3 g dl(-1) (4.2 and 10.1 mmol litre(-1)) were
      recorded. Compared with the reference method, bias (precision) was 0.2 (0.2) g
      dl(-1) [0.1 (0.1) mmol litre(-1)] for HcueArt, 0.8 (0.3) g dl(-1) [0.5 (0.2) mmol
      litre(-1)] for HbSat, 0.5 (0.5) g dl(-1) [0.3 (0.3) mmol litre(-1)] for HcueCap
      and 1.0 (1.2) g dl(-1) [0.6 (0.7) mmol litre(-1)] for SpHb. None of the devices
      tested would have led to unnecessary or delayed transfusion according to 2006 ASA
      transfusion criteria. Trend accuracy was better for HcueArt and HbSat than for
      HcueCap and SpHb. CONCLUSION: Bedside Hb measurement methods differ in their
      agreement to a laboratory haematology analyser but none would have led to
      transfusion errors. Trial Registry Number RCB 2009-AO1144-53.

PMID- 23869109
TI  - Efficient Gaussian process regression for large datasets.
AB  - Gaussian processes are widely used in nonparametric regression, classification
      and spatiotemporal modelling, facilitated in part by a rich literature on their
      theoretical properties. However, one of their practical limitations is expensive
      computation, typically on the order of n3 where n is the number of data points,
      in performing the necessary matrix inversions. For large datasets, storage and
      processing also lead to computational bottlenecks, and numerical stability of the
      estimates and predicted values degrades with increasing n. Various methods have
      been proposed to address these problems, including predictive processes in
      spatial data analysis and the subset-of-regressors technique in machine learning.
      The idea underlying these approaches is to use a subset of the data, but this
      raises questions concerning sensitivity to the choice of subset and limitations
      in estimating fine-scale structure in regions that are not well covered by the
      subset. Motivated by the literature on compressive sensing, we propose an
      alternative approach that involves linear projection of all the data points onto
      a lower-dimensional subspace. We demonstrate the superiority of this approach
      from a theoretical perspective and through simulated and real data examples.

PMID- 23869106
TI  - The role of the posterior cingulate cortex in cognition and disease.
AB  - The posterior cingulate cortex is a highly connected and metabolically active
      brain region. Recent studies suggest it has an important cognitive role, although
      there is no consensus about what this is. The region is typically discussed as
      having a unitary function because of a common pattern of relative deactivation
      observed during attentionally demanding tasks. One influential hypothesis is that
      the posterior cingulate cortex has a central role in supporting internally
      directed cognition. It is a key node in the default mode network and shows
      increased activity when individuals retrieve autobiographical memories or plan
      for the future, as well as during unconstrained 'rest' when activity in the brain
      is 'free-wheeling'. However, other evidence suggests that the region is highly
      heterogeneous and may play a direct role in regulating the focus of attention. In
      addition, its activity varies with arousal state and its interactions with other
      brain networks may be important for conscious awareness. Understanding posterior
      cingulate cortex function is likely to be of clinical importance. It is well
      protected against ischaemic stroke, and so there is relatively little
      neuropsychological data about the consequences of focal lesions. However, in
      other conditions abnormalities in the region are clearly linked to disease. For
      example, amyloid deposition and reduced metabolism is seen early in Alzheimer's
      disease. Functional neuroimaging studies show abnormalities in a range of
      neurological and psychiatric disorders including Alzheimer's disease,
      schizophrenia, autism, depression and attention deficit hyperactivity disorder,
      as well as ageing. Our own work has consistently shown abnormal posterior
      cingulate cortex function following traumatic brain injury, which predicts
      attentional impairments. Here we review the anatomy and physiology of the region
      and how it is affected in a range of clinical conditions, before discussing its
      proposed functions. We synthesize key findings into a novel model of the region's
      function (the 'Arousal, Balance and Breadth of Attention' model). Dorsal and
      ventral subcomponents are functionally separated and differences in regional
      activity are explained by considering: (i) arousal state; (ii) whether attention
      is focused internally or externally; and (iii) the breadth of attentional focus.
      The predictions of the model can be tested within the framework of complex
      dynamic systems theory, and we propose that the dorsal posterior cingulate cortex
      influences attentional focus by 'tuning' whole-brain metastability and so adjusts
      how stable brain network activity is over time. 

PMID- 23869110
TI  - Relations Among Intimate Partner Violence, Maternal Depressive Symptoms, and
      Maternal Parenting Behaviors.
AB  - The authors examined the relations among intimate partner violence (IPV),
      maternal depressive symptoms, and maternal harsh intrusive parenting. Using a
      cross-lagged, autoregressive path model, they sought to clarify the
      directionality of the relations among these 3 variables over the first 2 years of
      the child's life. The results indicated that, in this diverse sample of families
      living in predominantly low-income rural communities (N = 705), higher levels of
      early IPV were associated with increases in maternal depressive symptoms, which
      in turn were associated with increases in maternal harsh intrusive parenting
      behaviors. These findings suggest that interventions aimed at improving the
      parenting of women exposed to domestic violence may want to simultaneously target
      IPV and depressive symptomatology.

PMID- 23869111
TI  - Heat Capacity of Spider Silk-like Block Copolymers.
AB  - We synthesized and characterized a new family of di-block copolymers based on the
      amino acid sequences of Nephila clavipes major ampulate dragline spider silk,
      having the form HABn and HBAn (n=1-3), comprising an alanine-rich hydrophobic
      block, A, a glycine-rich hydrophilic block, B, and a histidine tag, H. The
      reversing heat capacities, Cp(T), for temperatures below and above the glass
      transition, Tg, were measured by temperature modulated differential scanning
      calorimetry. For the solid state, we then calculated the heat capacities of our
      novel block copolymers based on the vibrational motions of the constituent
      poly(amino acid)s, whose heat capacities are known or can be estimated from the
      ATHAS Data Bank. For the liquid state, the heat capacity was estimated by using
      the rotational and translational motions in the polymer chain. Excellent
      agreement was found between the measured and calculated values of the heat
      capacity, showing that this method can serve as a standard by which to assess the
      Cp for other biologically inspired block copolymers. The fraction of beta sheet
      crystallinity of spider silk block copolymers was also determined by using the
      predicted Cp, and was verified by wide angle X-ray diffraction and Fourier
      transform infrared spectroscopy. The glass transition temperatures of spider silk
      block copolymer were fitted by Kwei's equation and the results indicate that
      attractive interaction exists between the A-block and B-block.

PMID- 23869112
TI  - A Symbolic Interaction Approach to Cigarette Smoking: Smoking Frequency and the
      Desire to Quit Smoking.
AB  - This study applies a symbolic interaction perspective to the investigation of
      smoking frequency and a person's desire to quit smoking cigarettes. Data derived
      from 485 Atlanta area adult smokers provide a diverse, community-based sample of
      married and single men and women, aged 18 to 70 years old with a range of income,
      education, and occupational experiences. Multiple regression was used to analyze
      the data in order to explore the influence of social demographic characteristics,
      social interaction, subjective assessments of health, self conceptions, and
      smoker identity on smoking frequency and quitting smoking. Findings include: (1)
      the relationship with a non-smoker and hiding smoking negatively impacted smoking
      frequency, while perceiving positive consequences from smoking has a positive
      effect on smoking frequency; and (2) perceiving positive consequences of smoking
      was negatively related to the desire to quit smoking, while a negative smoker
      identity has a positive influence on the desire to quit. Taken as a whole, the
      symbolic interaction-inspired variables exerted strong and independent effects on
      both smoking frequency and quitting smoking. Future smoking interventions should
      focus on meanings and perceived consequences of smoking in general, and on the
      smoker identity in the development of campaigns to encourage quitting cigarette
      smoking.

PMID- 23869113
TI  - Market Size and Innovation: Effects of Medicare Part D on Pharmaceutical Research
      and Development.
AB  - Recent evidence suggests that Medicare Part D increased prescription drug use
      among seniors, and increased pharmaceutical firms' revenues from sales. Previous
      studies also indicate that increases in market size induce pharmaceutical
      innovation. This paper assesses the impact of the Medicare Part D legislation on
      pharmaceutical research and development (R&D), using time-series data on the
      number of drugs entering preclinical and clinical development by therapeutic
      class and phase. We find that the passage and implementation of Medicare Part D
      is associated with significant increases in pharmaceutical R&D for therapeutic
      classes with higher Medicare market share.

PMID- 23869114
TI  - For Which Side the Bell Tolls: The Laterality of Approach-Avoidance Associative
      Networks.
AB  - The two hemispheres of the brain appear to play different roles in emotion and/or
      motivation. A great deal of previous research has examined the valence hypothesis
      (left hemisphere = positive; right = negative), but an increasing body of work
      has supported the motivational hypothesis (left hemisphere = approach; right =
      avoidance) as an alternative. The present investigation (N = 117) sought to
      provide novel support for the latter perspective. Left versus right hemispheres
      were briefly activated by neutral lateralized auditory primes. Subsequently,
      participants categorized approach versus avoidance words as quickly and
      accurately as possible. Performance in the task revealed that approach-related
      thoughts were more accessible following left-hemispheric activation, whereas
      avoidance-related thoughts were more accessible following right-hemispheric
      activation. The present results are the first to examine such lateralized
      differences in accessible motivational thoughts, which may underlie more
      "downstream" manifestations of approach and avoidance motivation such as
      judgments, decision making, and behavior.

PMID- 23869115
TI  - Heat waves in the United States: definitions, patterns and trends.
AB  - High temperatures and heat waves are related but not synonymous concepts. Heat
      waves, generally understood to be acute periods of extreme warmth, are relevant
      to a wide range of stakeholders because of the impacts that these events have on
      human health and activities and on natural environments. Perhaps because of the
      diversity of communities engaged in heat wave monitoring and research, there is
      no single, standard definition of a heat wave. Experts differ in which threshold
      values (absolute versus relative), duration and ancillary variables to
      incorporate into heat wave definitions. While there is value in this diversity of
      perspectives, the lack of a unified index can cause confusion when discussing
      patterns, trends, and impacts. Here, we use data from the North American Land
      Data Assimilation System to examine patterns and trends in 15 previously
      published heat wave indices for the period 1979-2011 across the Continental
      United States. Over this period the Southeast region saw the highest number of
      heat wave days for the majority of indices considered. Positive trends (increases
      in number of heat wave days per year) were greatest in the Southeast and Great
      Plains regions, where more than 12 % of the land area experienced significant
      increases in the number of heat wave days per year for the majority of heat wave
      indices. Significant negative trends were relatively rare, but were found in
      portions of the Southwest, Northwest, and Great Plains.

PMID- 23869116
TI  - Truncated Product Methods for Panel Unit Root Tests.
AB  - This paper proposes two new panel unit root tests based on Zaykin et al. (2002)'s
      truncated product method. The first one assumes constant correlation between p
      values and the second one uses sieve bootstrap to allow for general forms of
      cross-section dependence in the panel units. Monte Carlo simulation shows that
      both tests have reasonably good size and are powerful in cases of some very large
      p-values. The proposed tests are applied to a panel of real GDP and inflation
      density forecasts, resulting in evidence that professional forecasters may not
      update their forecast precision in an optimal Bayesian way.

PMID- 23869117
TI  - Our instructions, your intentions and our combined expectations...Is there a
      perfect article??

PMID- 23869118
TI  - Putting the best foot forward.

PMID- 23869119
TI  - Gene therapy in periodontics.
AB  - GENES are made of DNA - the code of life. They are made up of two types of base
      pair from different number of hydrogen bonds AT, GC which can be turned into
      instruction. Everyone inherits genes from their parents and passes them on in
      turn to their children. Every person's genes are different, and the changes in
      sequence determine the inherited differences between each of us. Some changes,
      usually in a single gene, may cause serious diseases. Gene therapy is 'the use of
      genes as medicine'. It involves the transfer of a therapeutic or working gene
      copy into specific cells of an individual in order to repair a faulty gene copy.
      Thus it may be used to replace a faulty gene, or to introduce a new gene whose
      function is to cure or to favorably modify the clinical course of a condition. It
      has a promising era in the field of periodontics. Gene therapy has been used as a
      mode of tissue engineering in periodontics. The tissue engineering approach
      reconstructs the natural target tissue by combining four elements namely:
      Scaffold, signaling molecules, cells and blood supply and thus can help in the
      reconstruction of damaged periodontium including cementum, gingival, periodontal
      ligament and bone. 

PMID- 23869120
TI  - Systemic anti-microbial agents used in periodontal therapy.
AB  - Periodontitis is an infectious disease with marked inflammatory response, leading
      to destruction of underlying tissues. The aim of periodontal therapy is to
      eradicate the pathogens associated with the disease and attain periodontal
      health. This is achieved by non-surgical and surgical therapy; however,
      mechanical debridement and topical application of antiseptics may not be helpful
      in all cases. In such cases, adjunctive systemic antibiotic therapy remains the
      treatment of choice. It can reach micro-organisms at the base of the deep
      periodontal pockets and furcation areas via serum, and also affect organisms
      residing within gingival epithelium and connective tissue. Before advising any
      anti-microbial agent, it is necessary to have knowledge of that agent. The aim of
      this review article is to provide basic details of each systemic anti-microbial
      agent used in periodontal therapy. The points discussed are its mode of action,
      susceptible periodontal pathogens, dosage, its use in treatment of periodontal
      disease, and mechanism of bacterial resistance to each anti-microbial agent. It
      might be of some help while prescribing these drugs. 

PMID- 23869121
TI  - Is immunesenescence a contributing factor for periodontal diseases?
AB  - Current concept in periodontal diseases (PDs) states that it is the host's
      response toward the periodontal pathogens which leads to tissue destruction and
      attachment loss. Hence the role of immune response in the progression and
      resolution of PD must be considered vital. Any alteration in the immune system
      disturbs the homeostasis of the periodontium. Decline in immune system is the
      hallmark of aging, leading to increased susceptibility of elderly individuals to
      bacterial infections. The periodontal apparatus which is being constantly exposed
      to plaque biofilm is more vulnerable to destruction in aged individuals. Ageing
      related alterations in immune system has been discussed elsewhere as a
      contributor to various chronic inflammatory diseases like atherosclerosis,
      preterm, and low birth weight, etc. This paper reviews on the possible role of
      aging in periodontal destruction through altered immunity. Aging has long been
      associated with altered systemic inflammation. It has been discussed whether (1)
      this systemic inflammation is a consequence of increased occurrence of chronic
      inflammatory diseases upon aging or (2) aging associated systemic inflammation
      leads to such diseases. The immune responses which are protective at the first
      stages of life might result detrimental in the elderly. Hence it might be very
      difficult to individuate genetic profiles that might allow to identify
      individuals with a major risk for one or more age related diseases. Taking this
      into consideration, the cause of PDs in elderly is addressed with a systemic
      approach in order to understand the complex interplay between the aging immunity
      and PDs. 

PMID- 23869122
TI  - A new classification system for gingival and palatal recession.
AB  - Various classifications have been proposed to classify gingival recession.
      Miller's classification of gingival recession is most widely followed. With a
      wide array of cases in daily clinical practice, it is often difficult to classify
      numerous gingival recession cases according to defined criteria of the present
      classification systems. To propose a new classification system that gives a
      comprehensive depiction of recession defect that can be used to include cases
      that cannot be classified according to present classifications. A separate
      classification system for palatal recessions (PR) is also proposed. This article
      outlines the limitations of present classification systems and also the inability
      to classify PR. A new comprehensive classification system is proposed to classify
      recession on the basis of the position of interdental papilla and
      buccal/lingual/palatal recessions. 

PMID- 23869123
TI  - Drug-induced gingival overgrowth: The nemesis of gingiva unravelled.
AB  - Drug-induced gingival overgrowth or enlargement manifests as abnormal growth of
      the gingiva due to an adverse drug reaction (ADR) in patients treated with
      anticonvulsants, immunosuppressants, and calcium channel blockers. As gingival
      enlargement develops, it affects the normal oral hygiene practice and may
      interfere with masticatory functions. It gradually becomes a source of pain and
      the condition often leads to disfiguration. Within the group of patients that
      develop this unwanted effect, there appears to be variability in the extent and
      severity of the gingival changes. It would seem pertinent to identify and explore
      possible risk factors and relating them with the treatment plan. This article
      throws light on respective drugs and their association with gingival overgrowth
      and approaches to treatment based on current knowledge and investigative
      observations. 

PMID- 23869124
TI  - The effect of MTAD, an endodontic irrigant, on fibroblast attachment to
      periodontally affected root surfaces: A SEM analysis.
AB  - BACKGROUND: Root surface debridement (RSD) is necessary to create an environment
      suitable for reattachment of the periodontium. Root surface conditioning may aid
      the formation of a biocompatible surface suitable for cell reattachment.
      BioPureTM MTAD (mixture of Doxycycline, citric acid and a detergent) is an
      endodontic irrigant with antibacterial properties and the ability to remove smear
      layer. It was hypothesized that MTAD may be useful for root surface conditioning.
      The efficacy of MTAD as a conditioner was measured by examining fibroblast
      attachment to root surfaces. MATERIALS AND METHODS: Thirty-two specimens of human
      teeth with advanced periodontal disease were used. The surfaces were root planed
      until smooth. Half of the specimens were treated with 0.9% saline and the other
      samples with Biopure MTAD. As a negative control group, five further samples were
      left unscaled with surface calculus. Human gingival fibroblast cells HGF1-PI1
      were cultured and poured over the tooth specimens and incubated. After fixation,
      the samples were sputter-coated with gold and examined with a SEM. The morphology
      and number of attached, fixed viable cells were examined. The data was analysed
      using the Mann-Whitney-U statistical test. RESULTS: There was no significant
      difference between the numbers of attached cells in the experimental group
      treated with MTAD and the control group treated with saline. Little or no
      attached cells were seen in the negative control group. CONCLUSION: RSD created
      an environment suitable for cell growth and attachment in a laboratory setting.
      The use of MTAD did not promote the attachment and growth of cells on the surface
      of human roots following RSD.

PMID- 23869125
TI  - Efficacy of a commercially available multi-herbal formulation in periodontal
      therapy.
AB  - OBJECTIVE: This prospective clinical trial was designed to evaluate the clinical
      effects of a commercially available powder (Periocare((r)) Gum massage powder),
      containing various herbal medicaments, in the reduction of plaque and gingival
      inflammation in subjects diagnosed with gingivitis. MATERIALS AND METHODS:
      Seventy-five subjects diagnosed with chronic generalized gingivitis were selected
      and randomly divided into the following three groups: Group I - Scaling +
      Periocare((r)) Gum Massage powder, Group II - Periocare((r)) Gum Massage powder
      alone, and Group III - Scaling only. Clinical evaluation was done at baseline, 2
      weeks, 4 weeks, and 6 weeks using gingival index, plaque index, and
      microbiological culturing of plaque samples. RESULTS: Periocare((r)) Gum Massage
      (multi-herbal formulation) powder as an adjunct to mechanical therapy (scaling)
      showed significant clinical and microbiological improvement in the gingival index
      and plaque index scores as compared to other groups. Periocare((r)) Gum Massage
      powder as a monotherapy did not prove to be effective for plaque control.
      CONCLUSION: Periocare((r)) Gum Massage may be a useful herbal formulation for
      chemical plaque control and improvement in plaque scores and gingival status.

PMID- 23869126
TI  - Green tea extract as a local drug therapy on periodontitis patients with diabetes
      mellitus: A randomized case-control study.
AB  - BACKGROUND: The green tea extract is a naturally occurring product having
      beneficial effects that counteract with the pathobiological features of
      periodontitis and diabetes mellitus. Hence, the present study was aimed at
      incorporation of green tea extract into hydroxylpropyl methylcellulose and
      investigates its efficacy in chronic periodontitis patients associated with and
      without diabetes mellitus. MATERIALS AND METHODS: For the in vitro study,
      formulation of green tea strips and placebo strips, and analysis of drug release
      pattern from the green tea strips at different time intervals were performed. For
      the in vivo study, 50 patients (20-65 years), including 25 systemically healthy
      patients with chronic periodontitis (group 1) and 25 diabetic patients with
      chronic periodontitis (group 2) were enrolled. In each patient, test and control
      sites were identified for the placement of green tea and placebo strips,
      respectively. Gingival Index (GI), Probing Pocket Depth (PPD), and Clinical
      Attachment Level (CAL) were examined at baseline, first, second, third, and
      fourth weeks. Microbiological analysis for Porphyromonas gingivalis and
      Aggregatibacter actinomycetemcomitans was performed at baseline and fourth week.
      RESULTS: The in vitro study showed 10.67% green tea release at 30 min;
      thereafter, a slow release was noted till 120 min. IN VIVO STUDY: Both groups
      showed significant reduction in GI scores at the test sites. Group 1 showed
      significant (P < 0.001) PPD reduction at different time intervals at the test
      sites. However, group 2 showed significant reduction from baseline (5.30 +/-
      0.70) to fourth week (3.5 +/- 0.97). Statistically significant gain in CAL at the
      test sites was observed both in group 1 (1.33 mm) and group 2 (1.43 mm). The
      prevalence of P. gingivalis in group 1 test sites was significantly reduced from
      baseline (75%) to fourth week (25%). CONCLUSIONS: Local drug delivery using green
      tea extract could be used as an adjunct in the treatment of chronic periodontitis
      in diabetic and non-diabetic individuals.

PMID- 23869127
TI  - Evaluation of the efficacy of green tea catechins as an adjunct to scaling and
      root planing in the management of chronic periodontitis using PCR analysis: A
      clinical and microbiological study.
AB  - BACKGROUND: Increased knowledge of anaerobic bacteria in the development of
      periodontal diseases has led to new treatment strategies aiming primarily at
      suppression or elimination of specific periodontal pathogens. Over the last few
      decades, green tea has been subjected to many scientific and medical studies.
      AIM: The purpose of the present study was to assess the effect of green tea
      catechins on the red complex organisms using Polymerase Chain Reaction for
      microbiological analysis. MATERIALS AND METHODS: A split mouth study was
      conducted, in which a total of 20 subjects were included. Green tea catechin as
      local drug delivery was placed at study sites. Clinical parameters namely probing
      pocket depth (PPD), gingival index (GI), plaque index (PI) were recorded. Sub
      gingival plaque samples were collected, and red complex micro-organisms were
      studied using PCR. Clinical and microbiological parameters were recorded at
      baseline, 1(st), and 5(th) week after treatment. RESULTS: The results showed
      statistically significant difference in PPD, GI, and PI and significant reduction
      of red complex organisms from baseline to 1(st) week and baseline to 5(th) week
      in both study and control groups (P < 0.001). Intergroup comparison between study
      and control group was statistically insignificant for PPD, PI, and GI. A
      significantly greater reduction in Tannerella forsythus (Tf) at 1(st) week and
      5(th) week and Porphyromonas gingivalis (Pg) at 1(st) week was observed in study
      group when compared to control group. CONCLUSION: Green tea catechin can be used
      as an effective local drug delivery along with scaling and root planing in
      treatment of chronic periodontitis.

PMID- 23869128
TI  - Evaluation of the association between chronic periodontitis and acute coronary
      syndrome: A case control study.
AB  - BACKGROUND: The periodontal tissues mount an immune inflammatory response to
      bacteria and their products and the systemic challenge with these agents also
      induce a major vascular response. Although many studies have found a correlation
      between chronic periodontitis and cardiovascular diseases, the role of infection
      in acute coronary syndrome is disputed. The aim of this study is to investigate
      whether there is an association between chronic periodontitis and acute coronary
      syndrome. MATERIALS AND METHODS: A total of 30 patients, ages ranging from 30 
      80. 15 patients from A. B. Shetty Memorial Institute of Dental Sciences and 15
      patients admitted to Coronary Care Unit of Justice K. S. Hegde Charitable
      Hospital Deralakatte Mangalore were included in the study. Variables age more
      than 40 and gender were also analyzed. RESULTS: Of the 30 patients analyzed in
      this study, periodontitis was recognized in 11 patients of the acute coronary
      syndrome group and 10 patients in the healthy group. Fisher's exact test yielded
      a p value of 0.4539 with an odds ratio of 0.727(95% confidence interval 0.151 to
      3.493). CONCLUSION: No significant association was found between periodontal
      disease and acute coronary syndrome. Periodontitis may contribute to
      cardiovascular disease and stroke in susceptible subjects. Properly powered
      longitudinal case control and intervention trials are needed to identify how
      periodontitis and periodontal interventions may have an impact on cardiovascular
      diseases.

PMID- 23869129
TI  - Chromogranin A: Novel biomarker between periodontal disease and psychosocial
      stress.
AB  - CONTEXT: The psychosocial stress has long been regarded as a significant pre
      disposing factor for periodontal disease. The association between the periodontal
      disease and the neuroendocrine hormones has been observed. Chromogranin A (CgA)
      is supposed to link the activity of the neuroendocrine system to local and
      systemic immune functions and to be related to periodontitis. AIMS: The aim of
      this study was to determine the CgA levels in saliva and plasma in periodontal
      health and disease and to assess their potential relationship to periodontitis.
      SETTINGS AND DESIGNS: In this case-control study, the association between
      periodontal disease and stress marker has been assessed. MATERIALS AND METHODS:
      SIXTY SUBJECTS WERE CHOSEN FOR THIS STUDY: With case group comprising of 30
      subjects with chronic periodontitis and control group comprising of 30 healthy
      subjects. Salivary and plasma CgA levels were determined by ELISA technique.
      Clinical parameters included were plaque index, papillary bleeding index and
      clinical attachment loss and probing depth. Correlation analysis was calculated
      by independent sample t-test. RESULTS: Significantly higher CgA levels were found
      in saliva and plasma of patients with chronic periodontitis compared with healthy
      individuals (P < 0.05). No significant difference were observed between salivary
      and plasma CgA levels. CONCLUSIONS: The elevated level CgA in the plasma and
      saliva of subjects with stress induced chronic periodontitis has yielded insights
      into biological plausible association between the psychosocial stress and chronic
      periodontitis. Thus, our results suggest that CgA is a useful biomarker for
      evaluating at least in part the etiopathogenesis of periodontitis.

PMID- 23869130
TI  - A study to evaluate mobility of teeth during menstrual cycle using Periotest.
AB  - BACKGROUND AND OBJECTIVE: Over a century, an increased prevalence of gingival
      disease associated with increasing plasma sex steroid hormone levels has been
      reported. These situations present unique challenges to the oral health care
      professional. It is believed that hormonal fluctuations such as those associated
      with pregnancy, menstruation, and use of hormonal contraceptives lead to an
      increase in tooth mobility. However, this effect of female sex hormones on
      periodontal ligament and tooth supporting alveolar bone has rarely been
      investigated. So this study was undertaken to understand the effect on tooth
      mobility because of hormonal changes during the menstrual cycle. MATERIALS AND
      METHODS: The mobility of index teeth 16, 13, 21, 23, 24, 36, 33, 41, 43, and 44
      was measured with Periotest in 50 females at menstruation, ovulation, and
      premenstruation time points. Simplified oral hygiene index, plaque index,
      gingival index, and probing depth were also evaluated during the different phases
      of menstrual cycle for each subject participating in the study. STATISTICAL
      ANALYSIS: The results of the study were subjected to statistical analysis. Data
      analysis was done by applying Z test for comparing difference between two sample
      means. RESULT: The stages of menstrual cycle had no significant influence on the
      Periotest value. Despite no significant change in plaque levels, GI was
      significantly higher during ovulation and premenstruation time points.
      CONCLUSION: No change in tooth mobility was seen during the phases of the
      menstrual cycle. However, an exaggerated gingival response was seen during
      ovulation and premenstruation time when the entire menstrual cycle was observed.

PMID- 23869131
TI  - A need to educate postmenopausal women of their periodontal health.
AB  - BACKGROUND: Postmenopausal women have shown proactive willingness to take
      responsibility for their changing health care needs. The example of osteoporosis
      is a model that when educated of their bone health status, this cohort follows
      through with prevention and treatment regimens. Postmenopausal status is
      considered to be a risk factor for periodontitis. It is known that up to 50% of
      periodontal disease goes undiagnosed. The goal of periodontal therapy is to
      prevent tooth loss. OBJECTIVE: Is there a need, then to educate and inform
      postmenopausal women of their periodontal status? Can dentists provide a greater
      service to this cohort by increasing education and information? MATERIALS AND
      METHODS: The current study compares patient perception to actual clinical
      findings in 94 postmenopausal women. Patients are informed of their diagnosis,
      and educated about the disease, its risk factors and preventive and treatment
      modalities. Detailed interviews examine the patient intentions to follow up on
      preventive and treatment regimens suggested. RESULTS: Although 97.8% of
      participants reported having "healthy gums", 36.2% had severe periodontitis in at
      least one site. Interviews reveal that patients associated disease with abscess,
      and would be likely to follow prevetive and treatment regimens when they were
      informed of their diagnosis and educated on the topic. CONCLUSION: The findings
      suggest a need to make education a priority when treatment postmenopausal women.

PMID- 23869132
TI  - Clinical evaluation of porous hydroxyapatite bone graft (Periobone G) with and
      without collagen membrane (Periocol) in the treatment of bilateral grade II
      furcation defects in mandibular first permanent molars.
AB  - BACKGROUND: Furcation invasions represent one of the most demanding therapeutic
      challenges in periodontics. This investigation assessed and compared the clinical
      efficacy of hydroxyapatite bone graft material when used alone and with collagen
      membrane in the treatment of grade II furcation defects. MATERIALS AND METHODS:
      Ten patients with comparable bilateral furcation defects in relation to
      mandibular first molars were selected and treated in a split-mouth design. After
      the hygiene phase of therapy was completed, the groups were selected randomly
      either for treatment with hydroxyapatite bone graft (Periobone G) alone or with a
      combination of bone graft and guided tissue regeneration (GTR) membrane
      (Periocol). Clinical parameters like plaque index, gingival index, vertical
      probing depth, horizontal probing depth, clinical attachment level, position of
      marginal gingiva, and the amount of bone fill were used at baseline and at 3 and
      6 months postoperatively. RESULTS: At 6 months, both surgical procedures resulted
      in statistically significant reduction in vertical and horizontal probing depths
      and gain in the clinical attachment level. CONCLUSION: The use of combination
      technique yielded superior results compared to sites treated with bone graft
      alone. However, the difference was not statistically significant.

PMID- 23869133
TI  - Periodontal management of gingival enlargement associated with Sturge-Weber
      syndrome.
AB  - The Sturge-Weber syndrome is a rare uncommon neurocutaneous disorders with
      angiomas involving the leptomeninges (Leptomeningeal Angiomas) and skin of the
      face, typically in the ophthalmic (V1) and maxillary (V2) distributions of the
      trigeminal nerve. The cutaneous angioma is called a Port-Wine Stain. It is
      commonly referred to as "Sturge-Weber syndrome after Sturge and Weber who first
      described this affliction in 1879. This article present a case of Sturge-Weber
      syndrome associated with gingival enlargement, its management and follow-up
      results. 

PMID- 23869134
TI  - Intramucosal melanotic nevi - A case report of an unusual gingival enlargement.
AB  - Intramucosal melanotic nevus with multiple polypoid presentations in oral cavity
      is rare; though single nevus is not uncommon. Nevi are benign proliferations of
      nevus cells either in the epithelium or in the subepithelial stroma. They are
      best categorized as hamartomas rather than true neoplasm. We present a case of
      intramucosal melanotic nevi in a 26-year-old male patient, which clinically
      resembled hereditary fibrous gingival enlargement. 

PMID- 23869135
TI  - Long term follow up of idiopathic gingival enlargement associated with chronic
      periodontitis: A case report and review.
AB  - BACKGROUND: Idiopathic gingival enlargement is a rare condition characterized by
      massive enlargement of the gingiva. It may be associated with other
      diseases/conditions characterizing a syndrome, but rarely associated with
      periodontitis. CASE DESCRIPTION: This case report describes an unusual clinical
      form of gingival enlargement associated with chronic periodontitis. Clinical
      examination revealed diffuse gingival enlargement. The lesion was asymptomatic,
      firm, and pinkish red. Generalized periodontal pockets were observed.
      Radiographic evaluation revealed generalized severe alveolar bone loss.
      Histopathological investigations revealed atrophic epithelium with dense
      fibrocollagenous tissue. Lesions healed successfully following extraction and
      surgical excision, and no recurrence was observed after 1 year follow-up but
      recurrence was observed at 3 and 5-years follow-up. CLINICAL IMPLICATIONS:
      Successful treatment of idiopathic gingival enlargement depends on proper
      identification of etiologic factors and improving esthetics and function through
      surgical excision of the over growth. However, there may be recurrence.

PMID- 23869136
TI  - Gingival enlargement as an early diagnostic indicator in therapy-related acute
      myeloid leukemia: A rare case report and review of literature.
AB  - Treatment for Hodgkin's lymphoma (HL) has resulted in excellent survival rates
      but is associated with increased risks of secondary therapy-related acute myeloid
      leukemia (t-AML). Gingival enlargement associated with bleeding and ulceration is
      the most common rapidly appearing oral manifestations of leukemic involvement. An
      8 months pregnant patient reported with generalized gingival enlargement, with
      localized cyanotic and necrotic papillary areas. Co-relating the hematological
      report with the oral lesions and her past medical history of HL, a diagnosis of t
      AML secondary to treatment for HL was made by the oncologist. As oral lesions are
      one of the initial manifestations of acute leukemia, they may serve as a
      significant diagnostic indicator for the dental surgeons and their important role
      in diagnosing and treating such cases. Furthermore, this case report highlights
      the serious complication of t-AML subsequent to HL treatment and the important
      role that a general and oral health care professional may play in diagnosing and
      treating such cases. 

PMID- 23869137
TI  - Periodontal manifestations of von Recklinghausen neuro fibromatosis.
AB  - Neurofibroma is an uncommon benign tumor of the oral cavity derived from the
      cells that constitute the nerve sheath neurofibromatosis type 1 (NF1), also known
      as von Recklinghausen's disease, is the most common type of neurofibromatosis and
      accounts for about 90% of all cases. It is one of the most frequent human genetic
      diseases, with the prevalence of one case in 3,000 births. Neurofibroma is seen
      either as a solitary lesion or as part of the generalized syndrome of
      neurofibromatosis. The solitary form does not differ from the disseminated form
      or the multiple form of the disease, except that systemic and hereditary factors
      present in the disseminated form are absent in the solitary type. Oral cavity
      involvement by a solitary and peripheral plexiform neurofibroma in patients with
      no other signs of neurofibromatosis is uncommon. The expressivity of NF1 is
      extremely variable, with manifestations ranging from mild lesions to several
      complications and functional impairment. Oral manifestations can be found in
      almost 72% of NF1 patients. This is a case report of a 40-year-old lady with a
      history of multiple faint rounded densities in the skin, chest pain occasionally
      since 8 months and breathlessness since 1 year and swelling of the right side of
      the angle of the mandible with limited mouth opening. 

PMID- 23869138
TI  - Cryosurgery by tetrafluoroethane: An answer to black gums.
AB  - To highlight the effect of 1,1,1,2 tetrafluoroethane (TFE), a new material for
      cryosurgery of gingival melanin pigmentation (GMP). Five patients were treated
      using a TFE-cooled swab and the pre- and post-treatment photographs were
      compared. Complete keratinization took place in 3-4 weeks after application
      without any trace of pigmentation. During the follow-up period, no side effects
      were observed and the improved esthetics were maintained upto 1 year. 

PMID- 23869139
TI  - A novel approach in root coverage - Coronally repositioned flap with GTR membrane
      and frenotomy.
AB  - This case report describes a guided tissue regeneration (GTR) based root coverage
      procedure over maxillary central incisor using coronally advanced flap with
      simultaneously performed frenotomy. The patient was a 32-year-old female with
      chief complaint of gingival enlargement in relation to 11. Based on overall
      findings it was diagnosed as a case of inflammatory gingival enlargement.
      Vertical osseous defect along with Millers class I gingival recession was seen
      after initial therapy. GTR-based root coverage procedure using coronally advanced
      flap with simultaneously performed frenotomy was planned. Complete root coverage
      was achieved over the maxillary central incisor that initially presented with
      Miller's class I gingival recession along with radiographic bone fill of the
      osseous defect. This case report shows the possibility of applying GTR-based root
      coverage procedure using coronally advanced flap combined with frenotomy to treat
      Millers class I gingival recession. 

PMID- 23869140
TI  - Vestibular deepening by periosteal fenestration and its use as a periosteal
      pedicle flap for root coverage.
AB  - Gingival recession along with reduced width of attached gingiva and inadequate
      vestibular depth is a very common finding. Multiple techniques have been
      developed to obtain predictable root coverage and to increase the width of
      attached gingiva. Usually, the width of gingiva is first increased and then the
      second surgery is caried out for root coverage. The newer methods of root
      coverage are needed, not only to reconstruct the lost periodontal tissues but
      also to increase predictability, reduce the number of surgical sites, reduce the
      number of surgeries and improve patient comfort. Hence, this paper describes a
      single stage technique for increasing the width of attached gingiva and root
      coverage by using the periosteal pedicle flap. 

PMID- 23869141
TI  - From the Editor's desk.

PMID- 23869142
TI  - Quality management systems for your in vitro fertilization clinic's laboratory:
      Why bother?
AB  - Several countries have in recent years introduced prescribed requirements for
      treatment and monitoring of outcomes, as well as a licensing or accreditation
      requirement for in vitro fertilization (IVF) clinics and their laboratories. It
      is commonplace for Assisted Reproductive Technology (ART) laboratories to be
      required to have a quality control system. However, more effective Total Quality
      Management systems are now being implemented by an increasing number of ART
      clinics. In India, it is now a requirement to have a quality management system in
      order to be accredited and to help meet customer demand for improved delivery of
      ART services. This review contains the proceedings a quality management session
      at the Indian Fertility Experts Meet (IFEM) 2010 and focuses on the creation of a
      patient-oriented best-in-class IVF laboratory. 

PMID- 23869143
TI  - Prevalence of hepatic steatosis in women with polycystic ovary syndrome.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome
      (PCOS) both are known to be associated with insulin resistance and metabolic
      syndrome (MS). The aim of the study was to determine the presence of NAFLD and
      associated factors of hepatic steatosis in women with PCOS. MATERIALS AND
      METHODS: A cross-sectional hospital based study of 54 women with PCOS and 55
      healthy controls who were age and weight matched were included. Anthropometric
      parameters, biochemical and hormonal investigations were done in all the
      patients. Insulin resistance was calculated by Homeostasis model assessment
      (HOMA). Abdominal ultrasonography and biochemical tests were used to determine
      the presence of hepatic steatosis after excluding other causes liver disease.
      RESULTS: Women with PCOS had a higher prevalence of hepatic steatosis (67% vs
      25%, P = 0.001) MS (35% vs. 7%, P < 0.01) and elevated transaminases (31% vs. 7%,
      P = 0.03) than controls. All patients with PCOS and controls with MS had presence
      of hepatic steatosis. Age, BMI, waist-hip ratio, HOMA-IR, HDL and PCOS diagnosis
      were the factors associated with presence of hepatic steatosis. CONCLUSION: NAFLD
      is commonly present in women with PCOS in combination with other metabolic
      derangements. Evaluation for liver disease should be considered at an earlier age
      in women with PCOS, particularly those who have an evidence of MS.

PMID- 23869144
TI  - Metformin-clomiphene citrate vs. clomiphene citrate alone: Polycystic ovarian
      syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in
      women that is associated with reproductive and metabolic disorders. OBJECTIVES:
      We compared the ovulation and conception rates after the treatment with
      clomiphene citrate (CC) alone and in combination with metformin in infertile
      patients presented with polycystic ovarian syndrome (PCOS). MATERIALS AND
      METHODS: This randomized controlled trial of independent cases and controls was
      conducted at the Department of Obstetrics and Gynecology, Hera General Hospital,
      Makkah, Saudi Arabia from February 01 to December 31, 2008. The 42 subjects
      diagnosed as PCOS were divided into group A and B (21 subjects in each) for
      management with CC + metformin and CC alone, respectively. Group A received 500
      mg three times a day of metformin continuously from the first cycle for 6 months
      or till pregnancy was confirmed. In both groups CC was started at a dose of 50 mg
      from day-2 till day-6 of the menstrual cycle. The dose of CC was increased to 100
      mg in second and 150 mg in third cycle, and then remained 150 mg for the
      remaining three cycles. With ovulation the dose of CC was unaltered in both
      groups. Data were analyzed using Statistical Package for the Social Sciences
      (SPSS) version 16. RESULTS: More than 50% females in both groups were had body
      mass index > 25. Group A achieved high rate of regular cycles, ovulation success,
      and conception than group B (71.4% vs. 38.1%; P = 0.03), (76.2% vs. 38.1%; P =
      0.021), and (66.6% vs. 28.6%; P = 0.01), respectively. CONCLUSION: Management
      with metformin + CC increased the ovulation and conception rates.

PMID- 23869145
TI  - Ketotifen, a mast cell blocker improves sperm motility in asthenospermic
      infertile men.
AB  - AIM: This study aimed to evaluate the efficacy of ketotifen on sperm motility of
      asthenospermic infertile men. SETTING AND DESIGN: It is a prospective study
      designed in vivo. MATERIALS AND METHODS: In this interventional experimental
      study, a total of 40 infertile couples with asthenospermic infertility factor
      undergoing assisted reproductive technology (ART) cycles were enrolled. The
      couples were randomly assigned to one of two groups at the starting of the cycle.
      In control group (n = 20), the men did not receive Ketotifen, while in experiment
      group (n = 20), the men received oraly ketotifen (1 mg Bid) for 2 months. Semen
      analysis, under optimal circumferences, was obtained prior to initiation of
      treatment. The second semen analysis was done 2-3 weeks after stopped ketotifen
      treatment and sperm motility was defined. Clinical pregnancy was identified as
      the presence of a fetal sac by vaginal ultrasound examination. STATISTICAL
      ANALYSIS USED: All data are expressed as the mean +/- standard error of mean
      (SEM). t test was used for comparing the data of the control and treated groups.
      RESULTS: The mean sperm motility increased significantly (from 16.7% to 21.4%)
      after ketotifen treatment (P < 0.001). This sperm motility improvement was more
      pronounced in the primary infertility cases (P < 0.003). The rate of pregnancy
      was 12.5% in infertile couples that their men receiving 1 mg/twice a day
      ketotifen. In 52% of infertile men's semen, the percentage of sperm motility was
      increased from 5% to 35% and this sperm motility improvement was also observed in
      33% of necrospermia (0% motility) cases. CONCLUSION: These results suggest that
      ketotifen may represent as a novel therapeutic approach to improve sperm motility
      in the infertile men with cause of asthenospermia or necrospermia.

PMID- 23869146
TI  - Does centrifugation and semen processing with swim up at 37 degrees C yield sperm
      with better DNA integrity compared to centrifugation and processing at room
      temperature?
AB  - AIM: To evaluate whether semen processing at 37 degrees C yield sperm with better
      DNA integrity compared to centrifugation and processing at room temperature (RT)
      by swim-up method. SETTINGS: This study was done at tertiary care center attached
      to Reproductive Medicine Unit and Medical College. DESIGN: Prospective pilot
      study. PATIENTS: Normozoospermic men (n = 50) undergoing diagnostic semen
      analysis. MATERIALS AND METHODS: Normozoospermic samples (World Health
      Organization, 2010 criteria) after analysis was divided into two aliquots (0.5 mL
      each); one was processed at 37 degrees C and the other at RT by swim-up method.
      DNA fragmentation of both samples post wash was calculated by acridine orange
      method. STATISTICAL ANALYSIS USED: The values of sperm DNA fragmentation were
      represented as mean and standard error (mean +/- SEM) of the mean. Paired t-test
      was used for calculating the sperm DNA integrity difference between post wash at
      RT and 37 degrees C. RESULTS: Statistically significant difference was not
      observed in post wash sperm DNA fragmentation values at 37 degrees C compared to
      RT. CONCLUSION: Our data represents that there was no significant difference in
      sperm DNA fragmentation values of samples processed at 37 degrees C and at RT.
      Hence, sperm processing at 37 degrees C does not yield sperm with better DNA
      integrity compared to centrifugation and processing at RT.

PMID- 23869147
TI  - Anti-mullerian hormone and antral follicle count as predictors of ovarian
      response in assisted reproduction.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that AMH and
      antral follicle count (AFC) are good predictors of ovarian response to controlled
      ovarian stimulation and to compare them. MATERIALS AND METHODS: This
      observational cross-sectional study included 56 subjects aged between 25 and 42
      years who were enrolled between 1(st) January and 31(st) December 2010 for their
      first intracytoplasmic sperm injection (ICSI) program. Baseline hormone profiles
      including serum levels of Estradiol (E2), Follicle-stimulating hormone (FSH),
      Luteinizing hormone (LH), and Anti-mullerian Hormone (AMH) were determined on day
      3 of the previous cycle. The antral follicle count measurements were performed on
      days 3-5 of the same menstrual cycle. Antral follicles within the bilateral
      ovaries between 2-6 mm were recorded. The subjects were treated with long
      protocol for ovarian stimulation. Ovulation was induced with 10,000 IU of human
      chorionic gonadotropin (hCG) when at least 3 follicles attained the size of more
      than 17 mm. Transvaginal oocyte retrieval was performed under ultrasound guidance
      36 hours after hCG administration. An oocyte count less than 4 and absence of
      follicular growth with controlled ovarian hyper stimulation was considered as
      poor ovarian response. Oocyte count of 4 or more was considered as normal ovarian
      response. RESULTS: Statistical analysis was performed using SPSS software trail
      version 16.0. Subjects were divided into 2 groups, depending on the ovarian
      response. The mean oocyte counts were 12.27 +/- 6.06 and 2.22 +/- 1.24 in normal
      and poor responders, respectively, (P = 001). Multiple regression analysis
      revealed AMH and antral follicle count as predictors of ovarian response (beta
      coefficient +/- SE for AMH was 1.618 +/- 0.602 (P = 0.01) and for AFC, it was,
      0.528 +/- 0.175 (P = 0.004). AFC was found to be a better predictor of ovarian
      response compared to AMH in controlled ovarian hyper stimulation. CONCLUSION: The
      observations made in this study revealed that both AMH and AFC are good
      predictors of ovarian response; AFC being a better predictor compared to AMH.

PMID- 23869148
TI  - Role of diagnostic hystero-laparoscopy in the evaluation of infertility: A
      retrospective study of 300 patients.
AB  - OBJECTIVE: To determine the role of diagnostic hysterolaparoscopy in the
      evaluation of infertility in tertiary care centres. MATERIALS AND METHODS: This
      retrospective study was conducted at two tertiary care centres (the infertility
      clinics of Sriram Chandra Bhanj Medical College and Prachi hospital at Cuttack,
      Odisha) throughout the year in 2008. Women aged 20-40 years with normal hormone
      profile without male factor infertility were included. RESULTS: Out of 300 cases,
      206 (69%) patients had primary infertility. While laparoscopy detected
      abnormalities in 34% of the cases, significant hysteroscopy findings were noted
      in 18% of cases. Together, diagnostic hysterolaparoscopy detected abnormalities
      in 26% of the infertile patients in both groups. While the most common
      laparoscopic abnormality was endometriosis (14%) and adnexal adhesion (12%) in
      primary and secondary infertile patients, respectively, hysteroscopy found
      intrauterine septum as the most common abnormality in both groups. CONCLUSIONS:
      Hysterolaparoscopy is an effective diagnostic tool for evaluation of certain
      significant and correctable tubo-peritoneal and intrauterine pathologies like
      peritoneal endometriosis, adnexal adhesions, and subseptate uterus, which are
      usually missed by other imaging modalities.

PMID- 23869149
TI  - Submucous fibroids and infertility: Effect of hysteroscopic myomectomy and
      factors influencing outcome.
AB  - BACKGROUND: Submucosal myomas are associated with infertility and may be treated
      by hysteroscopic resection. OBJECTIVE: The aim of this retrospective study was to
      analyze 37 subfertile patients who unnderwent hysteroscopic myomectomy in a
      tertiary care center with particular regard to their postprocedure reproductive
      outcome. MATERIALS AND METHODS: The entire patient group (n = 37) underwent the
      procedure between March 2004 and March 2010. The submucosal myomas were type 0 (n
      = 27), type 1 (n = 8), and type 2 (n = 2). The mean myoma size was 2.1 cm; mean
      duration of the procedure was 54 mins and mean follow-up was 26 +/- 10 months. 22
      patients had one or more associated infertility factors. RESULTS: The
      complication rate was 5.4%. 11 patients (29.7%) conceived after the procedure.
      The pregnancy rate was better when myoma was the exclusive etiology of
      infertility (40%), when the myoma was completely intracavitary (33.3%), when the
      lesion was >= 30 mm in size (50%), and there were no associated intramural
      fibroids. CONCLUSION: Hysteroscopic myomectomy is a safe procedure to enhance
      fertility especially in cases with unexplained infertility.

PMID- 23869150
TI  - Nicotine alters male reproductive hormones in male albino rats: The role of
      cessation.
AB  - OBJECTIVES: The use of nicotine through smoking remains a serious health problem.
      It has been associated with reduced fertility, although the mechanism responsible
      is still unclear. The present study was designed to investigate whether nicotine
      induced infertility is associated with altered male reproductive hormones in male
      albino rats. MATERIALS AND METHODS: Forty male rats were divided equally into
      five groups and treated orally for thirty days. Group I, which served as the
      control received 0.2 ml/kg normal saline, Group II and III received 0.5 mg/kg
      (low dose) and 1.0 mg/kg (high dose) body weight of nicotine, respectively. The
      fourth and fifth groups were gavaged with 0.5 mg/kg and 1.0 mg/kg body weight of
      nicotine but were left untreated for another 30 days. These groups served as the
      recovery groups. Serum was analyzed for testosterone, luteinizing hormone (LH),
      follicle stimulating hormones (FSH), and prolactin using radioimmunoassay.
      RESULTS: Results showed that nicotine administration significantly decreased (P <
      0.05) testosterone in the low and high treated groups and FSH in the high dose
      treated group when compared with the control group. There was a significant
      increase (P < 0.05) in mean LH and prolactin level in the high dose treated group
      when compared with the control. However, the values of the recovery groups were
      comparable with the control. CONCLUSION: The findings in this study suggest that
      nicotine administration is associated with distorted reproductive hormones in
      male rats although ameliorated by nicotine cessation. It is plausible that the
      decreased testosterone level is associated with testicular dysfunction rather
      than a pituitary disorder.

PMID- 23869151
TI  - Ovulation and rate of implantation following unilateral ovariectomy in mice.
AB  - OBJECTIVES: Removal of an ovary of any side of the body is called the unilateral
      ovariectomy (ULO). ULO models are used to analyze the existence of functional and
      physiological asymmetries between the ovaries, including the ovum implantation.
      MATERIALS AND METHODS: ULO was done in mice without any specification on their
      stages of the estrous cycle. The animals were mated between 3(rd) and 15(th) day
      after ULO to observe the consequence of ULO on ovulation and ovum implantation.
      RESULTS: Ovulation and number of implantation were decreased in proportion to
      single contralateral ovary if the animals were mated within 36 hrs of ULO. It
      resulted in increased weight of contralateral ovary due to hypertrophy, and also
      in compensatory ovulation, formation of corpus luteum (CL) that reached a peak
      after 14(th) and 15(th) day of ULO (sacrificed on 5(th) day of pregnancy i.e.,
      19(th) and 20(th) day of ULO) compared to animals undergone sham-surgery. Numbers
      of implantations were also increased progressively on the contralateral ovarian
      side and get to a peak after similar days of compensation. DISCUSSION AND
      CONCLUSION: Following ULO, the remaining ovary started to compensate within 5(th)
      to 6(th) day of ULO even during pregnancy. Ovarian histology also showed
      increased formation of CL which is a marker of rate of ovulation.

PMID- 23869152
TI  - Assisted reproduction in polycystic ovarian disease: A multicentric trial in
      India.
AB  - AIM: The aim of this study is to compare ovarian response, oocyte, embryo
      quality, ovarian hyperstimulation syndrome incidence, and pregnancy rates in
      polycystic ovary syndrome (PCOS) and non-PCOS group. MATERIALS AND METHODS: This
      was a prospective observational study on PCOS carried out in seven assisted
      reproduction centers in India between August 2008 and July 2010, as part of trial
      under the Indian Society of Assisted Reproduction. A total of 192 women (77 in
      the PCOS group and 115 in the non- PCOS group) undergoing in vitro
      fertilization/intracytoplasmic sperm injection were included. All women had long
      protocol and recombinant follicle-stimulating hormone stimulation. ANALYSIS: The
      mean number of follicles and oocytes was higher in PCOS group compared with non
      PCOS, being 27.2 (+/-8.8) and 13.6 (+/-5.3); 15.9 (+/-6.3) and 10.9 (+/-6.2),
      respectively. The recovery rates of oocytes and mature oocytes per follicle were
      less in the PCOS group which was 64% and 61.1%, respectively as opposed to 80.3%
      and 74.5%, respectively in non-PCOS group. The total numbers of top-quality
      embryos were less in the PCOS group. CONCLUSION: In PCOS women though the number
      of follicles was more, recovery of mature oocytes, top-quality embryos was less.
      Pregnancy rates were comparable in both groups.

PMID- 23869153
TI  - The effects of honey and vitamin E administration on apoptosis in testes of rat
      exposed to noise stress.
AB  - AIMS: A variety of stress factors are known to inhibit male reproductive
      functions. So this study was conducted in order to investigate the effects of
      honey and vitamin E on the germinative and somatic cells of testes of rats
      exposed to noise stress. MATERIALS AND METHODS: Mature male wistar rats (n = 24)
      were randomly grouped as follows: Group 1 (honey + noise stress), 2 (vitamin E +
      noise stress), 3 (noise stress,) and 4 as the control group. In groups 1, 2, and
      3, rats were exposed to noise stress. In groups 1 and 2, rats also were given
      honey and vitamin E, respectively, orally for 50 days. After that, the
      germinative and somatic cells of testes parenchyma were isolated by digesting the
      whole testes by a standard method. Next, viability, apoptosis, and necrosis of
      the cells were evaluated by TUNEL kit and flow cytometry. RESULTS: The rates of
      apoptosis and necrosis of the testicular cells were increased (P = 0.003 and P =
      0.001, respectively), but viability of these cells decreased in testes of rats
      exposed to noise stress (P = 0.003). However, administration of honey and vitamin
      E were significantly helpful in keeping the cells of testis parenchyma alive,
      which suffers from noise pollution (P < 0.05 and P < 0.05, respectively).
      CONCLUSIONS: Noise stress has negative influences on the cells of testicular
      tissue by increasing apoptotic and necrotic cells. However, the associated
      enhancement in healthy cells suggests that honey and vitamin E have positive
      influences on the testis parenchyma.

PMID- 23869154
TI  - Comparison of clinical outcomes following vitrified warmed day 5/6 blastocyst
      transfers using solid surface methodology with fresh blastocyst transfers.
AB  - OBJECTIVES: The literature regarding clinical outcomes following day 5/6
      vitrified warmed blastocysts transfer has been conflicting. We decided to
      evaluate and compare the clinical outcomes following vitrified warmed day 5/6
      blastocyst transfer using a solid surface vitrification protocol with fresh
      blastocyst transfers. SETTINGS: University teaching hospital. STUDY DESIGN: A
      total of 249 women were retrospectively analyzed: 146 fresh day 5 blastocyst
      (group 1), 57 day 5 vitrified warmed blastocyst (group 2), and 46 vitrified
      warmed day 6 blastocyst (group 3) transfer cycles. Vitrification was done using
      solid surface methodology (non immersion protocol). The main outcomes were
      implantation rates, clinical pregnancy, and live birth rate per embryo transfer.
      RESULTS: The baseline clinical characteristics were similar among all three
      groups. The implantation and clinical pregnancy rates following vitrified warmed
      day 6 blastocyst transfers (20.9% and 32.6%) were significantly lower as compared
      to day 5 fresh and vitrified warmed day 5 blastocyst transfers (40.3% and 56.1%,
      36.3%, and 52.6%). However, there was no significant difference in the live birth
      rates across the three groups (group 1: 37.6%, group 2: 40.3%, and group 3:
      28.2%). CONCLUSION: No statistically significant difference was observed in live
      birth rates between fresh day 5 blastocyst transfers and vitrified warmed day 5/6
      blastocyst transfers. Vitrification of blastocysts using solid surface
      methodology is an efficient method of cryopreservation.

PMID- 23869155
TI  - Impact of different embryo loading techniques on pregnancy rates in in vitro
      fertlization/embryo transfer cycles.
AB  - BACKGROUND: Embryo transfer (ET) technique is one of the important factors of in
      vitro fertlization success. Among the different steps in ET technique, less
      attention has been given to embryo loading (EL). The aim was to compare the
      impact of two different techniques of EL on pregnancy rate in IVF/ET cycles.
      MATERIALS AND METHODS: In this retrospective study, 144 and 170 patients were
      placed in groups A and B, respectively. In Group A, the embryos were drawn
      directly into the ET catheter from culture microdrop under the oil. In Group B,
      the embryos were transferred from culture microdrop into G2 medium in center-well
      dish. Then, the embryos were drawn into the catheter and finally transferred into
      the uterus. Both groups were adjusted for other parameters based on the EL
      technique. The main outcome measure was pregnancy rate. RESULTS: There were
      insignificant differences for etiology of infertility, source of sperm, type of
      stimulation protocol, percent of IVF or intracytoplasmic sperm injection type of
      ET catheter, cycles with good quality embryos and transferred embryos between two
      groups. The rate of both chemical and clinical pregnancy was higher in Group B
      compared to A, but the difference was insignificant (P = 0.09 and P = 0.1,
      respectively). CONCLUSION: It seems that there is no difference in the outcome by
      loading the embryo from microdrop or center-well dish.

PMID- 23869156
TI  - Clinical course of ectopic pregnancy: A single-center experience.
AB  - OBJECTIVES: The objective was to highlight the frequency, clinical profile, and
      predisposing factors of ectopic pregnancy (EP) in a general hospital. MATERIALS
      AND METHODS: This descriptive study was conducted at the Obstetrics and
      Gynaecology department of Hera General hospital, Makkah, Saudi Arabia, from July
      1, 2009 to December 29, 2010. Data were collected on chief medical complaints,
      sociodemographic characteristics, past obstetrics and gynecological history,
      management done, and outcome of management. Data were analyzed using Microsoft
      Office Excel (version 2007). RESULTS: Out of total 7564 pregnancies, 44 (0.58%)
      patients were diagnosed as EP. Out of 44, 22 (50%) patients presented within 24 h
      of onset of symptoms. Mean age was 28 +/- 7 years. Multigravida were predominant
      in 25 (57%), and 21 (48%) had gestational age of 6-8 weeks at the time of
      presentation; the common presenting features were amenorrhea (41, 93.2%),
      abdominal pain (39, 88.6%), and tenderness (38, 86%). Previous pelvic surgery
      (13, 29.5%), infertility treatment (11, 25%), and pelvic inflammatory disease
      (10, 22.7%) were the common predisposing factors. Twenty-five (57%) presented
      with ruptured EP and were operated within 24 h, and the remaining were kept under
      observation till further diagnosis. After confirming the diagnosis, 12/19
      underwent laparoscopy, whereas 7/19 received medical treatment. Surgery confirmed
      fallopian tube pregnancies in 35 (94.5%). No mortality was observed. CONCLUSION:
      Previous pelvic surgeries were the major etiological factor for EP. Other factors
      were infertility treatment and pelvic inflammatory disease. The most common site
      of EP was fallopian tubes.

PMID- 23869157
TI  - Complete imperforate tranverse vaginal septum with septate uterus: A rare
      anomaly.
AB  - The isolated, complete, transverse vaginal septum is one of the most infrequent
      anomalies of the female genital tract, and when it coexists with a septate
      uterus, it is even rarer. This report describes a case of transverse vaginal
      septum with septate uterus. A 12-year-old girl sought medical assessment because
      of severe cyclic lower abdominal cramping and pelvic pain. Local examination
      revealed a blind vaginal pouch of 2 cm and on rectal examination a tender pelvic
      mass was noted. Radiological examination showed transverse vaginal septum in the
      lower vagina with bicornuate uterus. Surgical resection of the vaginal septum was
      done under laparoscopic guidance. Hysteroscopy revealed presence of uterine
      septum which was resected by a resectoscope. Post-operative dilatation of vagina
      was done to prevent restenosis. Laparoscopic guided abdominoperineal approach is
      better in such a case as multiple mullerian anomalies may coexist with each
      other. 

PMID- 23869158
TI  - Successful live birth after rescue ICSI following failed fertilization.
AB  - In a conventional IVF cycle unexpected complete fertilization failure may occur
      in 10-25% of infertile women. To overcome this barrier of fertilization failure,
      some investigators have suggested intracytoplasmic sperm injection (ICSI) on day
      1 of an unfertilized mature oocyte, the so called "rescue ICSI". We report a case
      of fertilization failure followed by rescue ICSI resulting in a live birth.
      Although the success of rescue ICSI is still questionable, this procedure is
      worth an attempt in order to give the best chance to the couple in that cycle. 

PMID- 23869159
TI  - Oral contraceptive pills: A risk factor for retinal vascular occlusion in in
      vitro fertilization patients.
AB  - Retinal vascular occlusion is the most common cause of retinopathy leading to
      severe visual loss in all age groups. Central retinal vein occlusion (CRVO) is
      usually seen in older age group and is often associated with systemic vascular
      diseases. Although the exact cause and effect relationship has not been proven,
      central retinal vein occlusion has been associated with various systemic
      pathological conditions, hence a direct review of systems toward the various
      systemic and local factors predisposing the central retinal vein occlusion is
      advocated. We describe the development of central retinal venous occlusion with
      associated cystoid macular edema (CME) in two healthy infertile women who were
      recruited for in vitro fertilization cycle for infertility. Predisposing risk
      factors associated with central retinal vein occlusion are obesity, sedentary
      life style, smoking, and some systemic diseases such as hyperlipidemia,
      hypertension, associated autoimmune disorders e.g., antiphospholipid antibody
      syndrome, lupus, diabetes mellitus, cardiovascular disorders, bleeding or
      clotting disorders, vasculitis, closed-head trauma, alcohol consumption, primary
      open-angle glaucoma or angle-closure glaucoma. In our patients, they were ruled
      out afterdoing allpertaining investigations. The cases were managed with further
      avoidance of oral contraceptives and intra-vitreal injections of Bevacizumab
      (Avastin), an anti-vascular endothelial growth factor (anti-VEGF drug) and
      Triamcinolone acetonide (a long acting synthetic steroid). Hence, even if no
      systemic diseases are detected. Physical examinations are recommended
      periodically for young women on oral contraceptive pills. 

PMID- 23869160
TI  - Management of severe ovarian hyperstimulation syndrome with thawed plasma.
AB  - Severe ovarian hyperstimulation syndrome remains one of the life threatening
      complication of assisted reproductive technology. In refractory cases of late
      ovarian hyperstimulation syndrome (OHSS), clinicians are left with limited
      therapeutic options. We report a case of refractory OHSS which was managed
      successfully using thawed plasma. Thawed plasma transfusion could be potential
      therapeutic option for managing patients with severe ovarian hyperstimulation not
      responding to conventional treatment. 

PMID- 23869161
TI  - Buffering Effect of Parental Monitoring Knowledge and Parent-Adolescent
      Relationships on Consequences of Adolescent Substance Use.
AB  - When adolescents begin using substances, negative consequences are not always
      directly proportional to the amount used; heavy users may have few consequences
      whereas light users may have numerous consequences. This study examined how
      parental monitoring knowledge and parent-child relationship quality may serve as
      buffers against negative consequences when adolescents use substances. Self
      report questionnaires were administered to a community sample of 200 healthy
      adolescents and their parents at two time points, one year apart. Results suggest
      that both parental monitoring knowledge and parent-child relationship quality
      serve as buffers against negative consequences of substance use - but only when
      adolescents report high levels of monitoring knowledge or strong parent-child
      relationship quality. Results suggests adolescent perceived parental monitoring
      knowledge and parent-child relationship quality each act independently to buffer
      adolescents against negative consequences of substance use over a one-year
      period.

PMID- 23869162
TI  - Robust protective factors for Africa American youths who have a parent with
      depression.

PMID- 23869163
TI  - Femtosecond Fiber Lasers Based on Dissipative Processes for Nonlinear Microscopy.
AB  - Recent progress in the development of femtosecond-pulse fiber lasers with
      parameters appropriate for nonlinear microscopy is reviewed. Pulse-shaping in
      lasers with only normal-dispersion components is briefly described, and the
      performance of the resulting lasers is summarized. Fiber lasers based on the
      formation of dissipative solitons now offer performance competitive with that of
      solid-state lasers, but with the benefits of the fiber medium. Lasers based on
      self-similar pulse evolution in the gain section of a laser also offer a
      combination of short pulse duration and high pulse energy that will be attractive
      for applications in nonlinear bioimaging.

PMID- 23869164
TI  - Association of lysyl oxidase-like 1 gene common sequence variants in Greek
      patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma.
AB  - PURPOSE: Three common sequence variants in the lysyl oxidase-like 1 (LOXL1) gene
      were recently associated with pseudoexfoliation (PEX) and pseudoexfoliation
      glaucoma (PEXG) in populations from various parts of the world. In this study,
      the genetic association of these variants was investigated in Greek patients with
      PEX and PEXG. METHODS: The three LOXL1 single nucleotide polymorphisms (SNPs),
      one intronic (rs2165241) and two nonsynonymous coding SNPs (rs1048661: R141L and
      rs3825942: G153D), were genotyped in a total of 48 unrelated patients with PEX,
      35 patients with PEXG, and 52 healthy subjects who had normal findings in
      repeated ophthalmic examinations. A genetic association study was performed.
      RESULTS: Between the two coding SNPs, R141L did not show an association with PEX
      (p=0.297 for allele G, p=0.339 for genotype GG), whereas allele G of G153D showed
      a significant association (odds ratio [OR]=3.52, 95% confidence interval
      [CI]=1.735-7.166, p=3.24*10(-4) for allele G, p=0.004 for genotype GG). Likewise,
      for the intronic SNP of rs2165241, genotype TT (p=0.005) and its corresponding
      allele T (OR=2.99, 95% CI=1.625-5.527, p=3.53*10(-4)) showed a significant
      association with PEX. The allele G of G153D showed a significant association with
      PEXG (OR=3.74, 95% CI=1.670-8.387, p=0.001). The combined haplotype GGT,
      consisting of all three risk alleles, was associated with PEX (p=0.037),
      conferring a 1.8-fold of increased risk to the disease (OR=1.799, 95% CI=1.04
      3.13). Furthermore, the haplotype GGT presented in 39.8% of the patients with PEX
      and 26.9% of the controls. CONCLUSIONS: Certain genetic variants in LOXL1 confer
      risk for PEX in Greek populations, confirming in part findings in patients from
      Northern Europe.

PMID- 23869165
TI  - Mediator profiles in tears during the conjunctival response induced by allergic
      reaction in the nasal mucosa.
AB  - BACKGROUND: The allergic reaction occurring primarily in the nasal mucosa can
      induce a secondary conjunctival response of an immediate (SICR), late (SLCR), or
      delayed (SDYCR) type in some patients with allergic conjunctivitis (AC).
      OBJECTIVES: To investigate the concentration changes of histamine, tryptase,
      eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN),
      leukotrienes (LTB 4, LTC4, LTE4), myeloperoxidase (MPO), interferon-gamma (IFN
      gamma), and interleukins (IL-2, IL-4, IL-5) in tears during the SICR, SLCR, and
      SDYCR. METHODS: In 32 patients with AC, 11 SICR (p<0.01), 13 SLCR (p<0.001), and
      eight SDYCR (p<0.01) to nasal challenges with allergens (NPTs), the NPTs and 32
      control tests with PBS were repeated and supplemented with the determination of
      these factors in tears. RESULTS: The SICRs were associated with significant
      concentration changes in tears (p<0.05) of histamine, tryptase, ECP, LTC4, and IL
      4. The SLCRs were accompanied by significant changes in concentrations of
      histamine, ECP, LTB4, LTC4, MPO, IL-4, and IL-5. The SDYCRs were associated with
      significant concentration changes in tears (p<0.05) of LTB4, MPO, IFN-gamma, and
      IL-2. No significant changes in these factors were recorded in tears during the
      32 PBS controls (p>0.1) or in the ten control patients (p>0.1). CONCLUSIONS:
      These results provide evidence for causal involvement of nasal allergy in some
      patients with AC, inducing secondary conjunctival response of immediate (SICR),
      late SLCR, or delayed SDYCR type, associated with different mediator, cytokine,
      and cellular profiles in the tears, suggesting involvement of different
      hypersensitivity mechanisms. These results also emphasize the diagnostic value of
      nasal allergen challenge combined with monitoring of the conjunctival response in
      some patients with AC.

PMID- 23869167
TI  - Next-generation sequencing of mitochondrial targeted AAV transfer of human ND4 in
      mice.
AB  - PURPOSE: To determine the effects of mitochondrial targeting sequence (MTS)
      modified AAV gene delivery of wild-type human NADH dehydrogenase subunit 4 (ND4),
      mutated in most cases of the blinding disease Leber hereditary optic neuropathy
      (LHON), on the host mouse mitochondrial genome. METHODS: We injected a modified
      self-complementary (sc) AAV vector, to which we appended the cytochrome oxidase
      subunit 8 (COX8) leader to one of the three capsid proteins (VP2) comprising the
      protein shell of the AAV virion, into the mouse vitreous to deliver the human ND4
      gene under the control of a mitochondrial heavy strand promoter (HSP) directly to
      the mitochondria of the mouse retina. Control viruses consisting of scAAV lacking
      the COX8 targeting sequence and containing human ND4, or scAAV containing GFP,
      were also vitreally injected. Using next-generation sequencing of mitochondrial
      DNA extracted from the pooled mouse retinas of experimental and control eyes, we
      tested for the presence of the transferred human ND4, and any potential
      recombination of the transferred human ND4 gene with the endogenous host
      mitochondrial genome. RESULTS: We found hundreds of human ND4 DNA reads in
      mitochondrial samples of MTS AAV-ND4-injected eyes, a few human ND4 reads with
      AAV-ND4 lacking the MTS, and none with AAV-GFP injection. Putative chimeric read
      pairs at the 5' or 3' ends of human ND4 showed only vector sequences without the
      flanking mouse sequences expected with homologous recombination of human ND4 with
      the murine ND4. Examination of mouse mitochondrial ND4 sequences for evidence of
      intra-molecular small-scale homologous recombination events yielded no
      significant stretches greater than three to four nucleotides attributable to
      human ND4. Furthermore, in no instance did human ND4 insert into other non
      homologous sites of the 16 kb host mtDNA. CONCLUSIONS: Our findings suggest that
      human ND4 remains episomal in host mitochondria and is not disruptive to any of
      the endogenous mitochondrial genes of the host genome. Therefore, mitochondrial
      gene transfer with an MTS-AAV is non-mutagenic and likely to be safe if used to
      treat LHON patients with mutated ND4.

PMID- 23869166
TI  - Estrogen pathway polymorphisms in relation to primary open angle glaucoma: an
      analysis accounting for gender from the United States.
AB  - PURPOSE: Circulating estrogen levels are relevant in glaucoma phenotypic traits.
      We assessed the association between an estrogen metabolism single nucleotide
      polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG),
      accounting for gender. METHODS: We included 3,108 POAG cases and 3,430 controls
      of both genders from the Glaucoma Genes and Environment (GLAUGEN) study and the
      National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR)
      consortium genotyped on the Illumina 660W-Quad platform. We assessed the relation
      between the SNP panels representative of estrogen metabolism and POAG using
      pathway- and gene-based approaches with the Pathway Analysis by Randomization
      Incorporating Structure (PARIS) software. PARIS executes a permutation algorithm
      to assess statistical significance relative to the pathways and genes of
      comparable genetic architecture. These analyses were performed using the meta
      analyzed results from the GLAUGEN and NEIGHBOR data sets. We evaluated POAG
      overall as well as two subtypes of POAG defined as intraocular pressure (IOP)
      >=22 mmHg (high-pressure glaucoma [HPG]) or IOP <22 mmHg (normal pressure
      glaucoma [NPG]) at diagnosis. We conducted these analyses for each gender
      separately and then jointly in men and women. RESULTS: Among women, the estrogen
      SNP pathway was associated with POAG overall (permuted p=0.006) and HPG (permuted
      p<0.001) but not NPG (permuted p=0.09). Interestingly, there was no relation
      between the estrogen SNP pathway and POAG when men were considered alone
      (permuted p>0.99). Among women, gene-based analyses revealed that the catechol-O
      methyltransferase gene showed strong associations with HTG (permuted gene
      p<=0.001) and NPG (permuted gene p=0.01). CONCLUSIONS: The estrogen SNP pathway
      was associated with POAG among women.

PMID- 23869169
TI  - Current perspectives on tocilizumab for the treatment of rheumatoid arthritis: a
      review.
AB  - Rheumatoid arthritis (RA) remains a major clinical problem with many patients
      having continuing systemic inflammatory disease resulting in progressive erosive
      damage and high levels of disability. A range of pro-inflammatory cytokines
      including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 are involved
      in RA pathogenesis; these cytokines can be specifically inhibited by biological
      agents. Tocilizumab (TCZ) is a recombinant humanized anti-IL-6 receptor
      monoclonal antibody, administered monthly by intravenous infusion that prevents
      IL-6 signal transduction. There is strong evidence that it is both clinically
      efficacious and cost-effective. There have been several key clinical trials
      evaluating the safety and efficacy of TCZ in RA patients. We review five Phase II
      trials and seven Phase III trials enrolling a total of 626 and 5268 RA patients
      respectively. The American College of Rheumatology (ACR) response criteria were
      used as the primary or secondary outcome measure in all trials. Overall these
      trials demonstrated that TCZ was effective in the treatment of RA in a number of
      patient groups, including those with an inadequate response to methotrexate (MTX)
      or TNF inhibition. TCZ use, both as monotherapy and in combination with MTX,
      improved the signs and symptoms of RA within several weeks of commencing
      treatment. Additionally, TCZ was shown to reduce radiological disease progression
      and improve physical function, both as monotherapy and in combination with MTX. A
      5-year extension study demonstrated that TCZ sustained good long-term efficacy
      and safety profiles. TCZ was generally well tolerated. Although its use increased
      the risk of an adverse event, these were usually mild to moderate in severity and
      treatment did not increase the risk of a serious adverse event in comparison to
      controls. Due to moderate increases in serum levels of total cholesterol,
      triglycerides, high-density lipoproteins and serum transaminases seen in those
      patients treated with TCZ, as well as severe neutropenia in some, regular blood
      monitoring of full blood count, liver function and lipids is recommended. Given
      its clinical efficacy in the treatment of RA, TCZ may be beneficial in the
      treatment of other autoimmune diseases where IL-6 plays a role in the
      inflammatory cascade. 

PMID- 23869171
TI  - Cost-utility analysis for platinum-sensitive recurrent ovarian cancer therapy in
      South Korea: results of the polyethylene glycolated liposomal
      doxorubicin/carboplatin sequencing model.
AB  - OBJECTIVE: We performed a cost-utility analysis to assess the cost-effectiveness
      of a chemotherapy sequence including a combination of polyethylene glycolated
      liposomal doxorubicin (PLD)/carboplatin versus paclitaxel/carboplatin as a second
      line treatment in women with platinum-sensitive ovarian cancer. METHODS: A Markov
      model was constructed with a 10-year time horizon. The treatment sequence
      consisted of first- to sixth-line chemotherapies and best supportive care (BSC)
      before death. Cycle length, a time interval for efficacy evaluation of
      chemotherapy, was 9 weeks. The model consisted of four health states: responsive,
      progressive, clinical remission, and death. At any given time, a patient may have
      remained on a current therapy or made a transition to the next therapy or death.
      Median time to progressions and overall survivals data were obtained through a
      systematic literature review and were pooled using a meta-analytical approach. If
      unavailable, this was elicited from an expert panel (eg, BSC). These outcomes
      were converted to transition probabilities using an appropriate formula. Direct
      costs included drug-acquisition costs for chemotherapies, premedication, adverse
      event treatment and monitoring, efficacy evaluation, BSC, drug administration,
      and follow-up tests during remission. Indirect costs were transportation
      expenses. Utilities were also derived from the literature. Costs and utilities
      were discounted at an annual rate of 5% per cycle. RESULTS: PLD/carboplatin
      combination as the second line in the sequence is more effective and costly than
      paclitaxel/carboplatin combination, showing an additional US$21,658 per quality
      adjusted life years. This result was robust in a deterministic sensitivity
      analysis except when median time to progression of second-line therapies and
      administration cost of PLD/carboplatin per administration cycle were varied. The
      probability of cost-effectiveness for PLD/carboplatin combination was 49.4% at a
      willingness to pay $20,000. CONCLUSION: A PLD/carboplatin combination is an
      economically valuable option as second-line chemotherapy for the treatment of
      platinum-sensitive ovarian cancer in South Korea.

PMID- 23869172
TI  - Changes in quality of care and costs induced by implementation of a diabetes
      program in a social security entity of Argentina.
AB  - PURPOSE: To measure the impact of a diabetes and cardiovascular risk factors
      program implemented in a social security institution upon short- and long-term
      clinical/metabolic outcomes and costs of care. METHODS: Observational
      longitudinal cohort analysis of clinical/metabolic data and resource use of 300
      adult male and female program participants with diabetes before (baseline) and 1
      and 3 years after implementation of the program. Data were obtained from clinical
      records (Qualidiab) and the administration's database. RESULTS: The
      implementation of the program in "real world" conditions resulted in an immediate
      and sustainable improvement of the quality of care provided to people with
      diabetes incorporated therein. We also recorded a more appropriate oral therapy
      prescription for hyperglycemia and cardiovascular risk factors (CVRFs), as well
      as a decrease of events related to chronic complications. This improvement was
      associated with an increased use of diagnostic and therapeutic resources,
      particularly those related to pharmacy prescriptions, not specifically used for
      the control of hyperglycemia and other CVRFs. CONCLUSION: The implementation of a
      diabetes program in real-world conditions results in a significant short- and
      long-term improvement of the quality of care provided to people with diabetes and
      other CVRFs, but simultaneously increased the use of resources and the cost of
      diagnostic and therapeutic practices. Since controlled studies have shown
      improvement in quality of care without increasing costs, our results suggest the
      need to include management-control strategies in these programs for appropriate
      medical and administrative feedback to ensure the simultaneous improvement of
      clinical outcomes and optimization of the use of resources.

PMID- 23869173
TI  - Chronic fatigue in patients with unexplained self-reported food hypersensitivity
      and irritable bowel syndrome: validation of a Norwegian translation of the
      Fatigue Impact Scale.
AB  - BACKGROUND: Patients with unexplained self-reported food hypersensitivity and
      irritable bowel syndrome (IBS) suffer from several health complaints, including
      fatigue. The aim of the present study was to validate a Norwegian translation of
      the Fatigue Impact Scale (FIS), and to assess the impact of fatigue in patients
      with self-reported food hypersensitivity and IBS, as compared with healthy
      controls. METHODS: Thirty-eight patients with unexplained self-reported food
      hypersensitivity and IBS, who participated in the validation of the FIS completed
      the following additional questionnaires: the Short Form of Nepean Dyspepsia Index
      for assessment of quality of life, the Subjective Health Complaint Inventory, and
      questionnaires for diagnosis and severity of IBS. Impact of fatigue was studied
      in 43 patients with unexplained self-reported food hypersensitivity, 70%
      diagnosed with IBS, and 42 healthy controls. RESULTS: Cronbach's alpha for the
      FIS was 0.98, indicating excellent agreement between individual items. Scores on
      the FIS correlated with scores on the Short Form of Nepean Dyspepsia Index (r =
      0.50, P = 0.001), indicating good convergent validity, and were higher in
      patients (median 85.0, interquartile range 36.8-105.3) than in controls (median
      14.0, interquartile range 3.0-29.0, P <= 0.0001). CONCLUSION: The Norwegian
      translation of the FIS performed excellently in patients with unexplained self
      reported food hypersensitivity and IBS, with patients reporting significantly
      more impact of chronic fatigue than healthy controls.

PMID- 23869174
TI  - Risk factors of converting to laparotomy in laparoscopic appendectomy for acute
      appendicitis.
AB  - PURPOSE: Laparoscopic appendectomy (LA) for acute appendicitis has several
      advantages over open appendectomy (OA). In cases of complicated appendicitis, LA
      is converted to OA at a constant rate, though converting appendectomy (CA) has
      several disadvantages. We retrospectively determined preoperative risk factors
      for failure of LA and subsequent conversion to OA. METHODS: Consecutive cases of
      preoperative computed tomography (CT) and attempted LA were retrieved from our
      hospital database and grouped by procedure (LA versus CA). Patients with negative
      appendectomies (n = 28), opened appendectomy (n = 210), delayed interval
      appendectomy (n = 3), or who were <14 years of age were excluded. RESULTS:
      Average patient age, preoperative C-reactive protein (CRP) level, and diffuse
      peritonitis were significantly different between the groups. CT inflammation and
      occurrence of complicated appendicitis were significantly higher in CA than LA.
      Conversion to OA was mostly because of dense adhesions, diffuse peritonitis, and
      difficulties in excision of the appendix due to perforation or severe
      inflammation from surgical point of view. Postoperative complications were
      significantly lower in LA than CA, although the rate of intraoperative abscess
      was not different. CONCLUSION: Most patients with acute appendicitis can be
      successfully treated with LA. We identified the following significant risk
      factors of CA: CT inflammation grade 4 or 5; complicated appendicitis; higher
      preoperative CRP level; and diffuse peritonitis.

PMID- 23869170
TI  - Role of leptin resistance in the development of obesity in older patients.
AB  - Obesity is a global epidemic associated with aging-like cellular processes; in
      both aging and obesity, resistance to hormones such as insulin and leptin can be
      observed. Leptin is a circulating hormone/cytokine with central and peripheral
      effects that is released mainly by subcutaneous white adipose tissue. Centrally,
      leptin controls food intake, energy expenditure, and fat distribution, whereas it
      controls (among several others) insulin sensitivity, free fatty acids (FFAs)
      oxidation, and lipolysis in the periphery. Aging is associated with important
      changes in both the distribution and the composition of adipose tissue. Fat is
      redistributed from the subcutaneous to the visceral depot and increased
      inflammation participates in adipocyte dysfunction. This redistribution of
      adipose tissue in favor of visceral fat influences negatively both longevity and
      healthy aging as shown in numerous animal models. These modifications observed
      during aging are also associated with leptin resistance. This resistance blunts
      normal central and peripheral functions of leptin, which leads to a decrease in
      neuroendocrine function and insulin sensitivity, an imbalance in energy
      regulation, and disturbances in lipid metabolism. Here, we review how age-related
      leptin resistance triggers metabolic disturbances and affects the longevity of
      obese patients. Furthermore, we discuss the potential impacts of leptin
      resistance on the decline of brown adipose tissue thermogenesis observed in
      elderly individuals. 

PMID- 23869175
TI  - Cooled radiofrequency denervation for treatment of sacroiliac joint pain: two
      year results from 20 cases.
AB  - BACKGROUND: Sacroiliac joint pain is a common cause of chronic low back pain.
      Different techniques for radiofrequency denervation of the sacroiliac joint have
      been used to treat this condition. However, results have been inconsistent
      because the variable sensory supply to the sacroiliac joint is difficult to
      disrupt completely using conventional radiofrequency. Cooled radiofrequency is a
      novel technique that uses internally cooled radiofrequency probes to enlarge
      lesion size, thereby increasing the chance of completely denervating the
      sacroiliac joint. The objective of this study was to evaluate the efficacy of
      cooled radiofrequency denervation using the SInergyTM cooled radiofrequency
      system for sacroiliac joint pain. METHODS: The charts of 20 patients with chronic
      sacroiliac joint pain who had undergone denervation using the SInergyTM cooled
      radiofrequency system were reviewed at two years following the procedure. Outcome
      measures included the Numeric Rating Scale for pain intensity, Patient Global
      Impression of Change, and Global Perceived Effect for patient satisfaction.
      RESULTS: Fifteen of 20 patients showed a significant reduction in pain (a
      decrease of at least three points on the Numeric Rating Scale). Mean Numeric
      Rating Scale for pain decreased from 7.4 +/- 1.4 to 3.1 +/- 2.5, mean Patient
      Global Impression of Change was "improved" (1.4 +/- 1.5), and Global Perceived
      Effect was reported to be positive in 16 patients at two years following the
      procedure. CONCLUSION: Cooled radiofrequency denervation showed long-term
      efficacy for up to two years in the treatment of sacroiliac joint pain.

PMID- 23869176
TI  - New developments in the treatment of HER2-positive breast cancer.
AB  - Approximately 20%-30% of metastatic breast cancers show increased expression of
      the human epidermal growth factor receptor-2 (HER2) tyrosine kinase. Two HER2
      specific therapies are currently approved for clinical treatment of patients with
      HER2-overexpressing metastatic breast cancer. Trastuzumab is a monoclonal
      antibody against HER2 and is approved for first-line treatment of HER2-positive
      metastatic breast cancer. Lapatinib is a small molecule dual inhibitor of
      epidermal growth factor receptor and HER2 tyrosine kinases, and is approved for
      trastuzumab-refractory disease. Although trastuzumab is a highly effective
      therapy for patients with HER2-overexpressing metastatic breast cancer, a
      significant number of patients in the initial clinical trials of trastuzumab
      monotherapy showed resistance to trastuzumab-based therapy. Further, among those
      who did respond, the initial trials indicated that the median time to progression
      was less than 1 year. Similarly, lapatinib is effective in a subset of
      trastuzumab-refractory cases, but the majority of patients display resistance.
      This review discusses the multiple molecular mechanisms of resistance that have
      been proposed in the literature. In addition, novel agents that are being tested
      for efficacy against HER2-positive breast cancer, including the antibodies
      pertuzumab and trastuzumab-DM1 and the immunotoxin affitoxin, are reviewed. The
      introduction of trastuzumab has revolutionized the clinical care of patients with
      HER2-positive metastatic breast cancer and has resulted in dramatic reductions in
      recurrences of early-stage HER2-positive breast cancer. The development and
      implementation of gene- and protein-based assays that measure potential molecular
      predictors of trastuzumab resistance will allow individualization of HER2
      targeted therapeutic approaches, and may ultimately improve treatment of HER2
      positive breast cancer.

PMID- 23869177
TI  - New and emerging combination therapies for esophageal cancer.
AB  - Esophageal cancer comprises two different histological forms - squamous cell
      carcinoma (SCC) and adenocarcinoma (AC). While the incidence of AC has increased
      steeply in Western countries during the last few years, the incidence of SCC is
      fairly stable. Both forms differ in pathogenesis and response to chemotherapy and
      radiation therapy. Plenty of studies have evaluated new chemotherapy combination
      regimens in the neoadjuvant, adjuvant, and palliative setting. In addition, new
      radiation and chemoradiation protocols have been investigated. Finally, molecular
      targeted therapy has been included in several new randomized prospective trials.
      Therefore, this review presents new data on this topic and critically discusses
      promising approaches towards a more effective treatment in a disease with a grim
      prognosis. 

PMID- 23869178
TI  - Orphan G protein receptor GPR55 as an emerging target in cancer therapy and
      management.
AB  - G protein-coupled receptors (GPCRs) modulate a vast array of cellular processes.
      The current review gives an overview of the general characteristics of GPCRs and
      their role in physiological conditions. In addition, it describes the current
      knowledge of the physiological and pathophysiological functions of GPR55, an
      orphan GPCR, and how it can be exploited as a therapeutic target to combat
      various cancers. 

PMID- 23869179
TI  - Clinical effectiveness of baclofen for the treatment of alcohol dependence: a
      review.
AB  - Baclofen, an agonist at the B subunit of gaba-aminobutyric acid receptor,
      possesses pharmacologic properties that may confer utility for the treatment of
      alcohol dependence. Research suggests that not only can it be useful in promoting
      maintenance of alcohol abstinence but also it may play a key role in decreasing
      alcohol cravings and anxiety often associated with alcohol dependence. To assess
      the benefit of baclofen for alcohol dependence, a review of the literature was
      conducted to identify published data investigating this off-label treatment. Four
      randomized controlled trials to date have been published and were included in
      this review. Although primary outcomes differ between studies, patients
      randomized to baclofen experience higher rates of abstinence from alcohol than
      those taking placebo in two of the trials. Secondary analyses indicate that
      baclofen is safe in patients with alcohol dependence, including those with
      moderate to severe liver cirrhosis, and may provide beneficial anxiolytic
      effects. Despite some positive data, the largest available randomized controlled
      trial failed to find any differences between baclofen and placebo. In all
      studies, individuals with severe medical comorbidities, seizure disorders, and
      psychiatric disorders were excluded from trials, which may limit external
      validity. In summary, there may be beneficial effects from using baclofen for the
      treatment of alcohol dependence; however, limited conclusions can be drawn from
      the small number of studies currently available for review. Larger well-designed
      trials are needed to further define baclofen's role for the treatment of alcohol
      dependence. 

PMID- 23869180
TI  - Synthetic cathinone abuse.
AB  - The abuse of synthetic cathinones, widely known as bath salts, has been
      increasing since the mid-2000s. These substances are derivatives of the naturally
      occurring compound cathinone, which is the primary psychoactive component of
      khat. The toxicity of synthetic cathinones includes significant sympathomimetic
      effects, as well as psychosis, agitation, aggression, and sometimes violent and
      bizarre behavior. Mephedrone and methylenedioxypyrovalerone are currently the
      predominantly abused synthetic cathinones. 

PMID- 23869181
TI  - Space-time stick-breaking processes for small area disease cluster estimation.
AB  - We propose a space-time stick-breaking process for the disease cluster
      estimation. The dependencies for spatial and temporal effects are introduced by
      using space-time covariate dependent kernel stick-breaking processes. We compared
      this model with the space-time standard random effect model by checking each
      model's ability in terms of cluster detection of various shapes and sizes. This
      comparison was made for simulated data where the true risks were known. For the
      simulated data, we have observed that space-time stick-breaking process performs
      better in detecting medium- and high-risk clusters. For the real data, county
      specific low birth weight incidences for the state of South Carolina for the
      years 1997-2007, we have illustrated how the proposed model can be used to find
      grouping of counties of higher incidence rate.

PMID- 23869182
TI  - Effects of lipid emulsion and multivitamins on the growth of microorganisms in
      peripheral parenteral nutrition solutions.
AB  - BACKGROUND: Blood stream infections caused by Bacillus cereus or Serratia
      marcescens in patients receiving peripheral parenteral nutrition (PPN) have
      occasionally been reported in Japan, but these microorganisms are not major
      causes of blood stream infections in patients receiving total parenteral
      nutrition via a central venous catheter. In Japan, commercially available PPN
      solutions contain amino acids, glucose, and electrolytes, but not contain lipid
      emulsion (LE) and multivitamins (MV). In this study, the effects of LE and MV on
      the growth of microorganisms such as Bacillus cereus, Serratia marcescens,
      Staphylococcus aureus, and Candida albicans in PPN solutions were investigated.
      METHODS: A commercial 3% amino acid and 7.5% glucose solution with electrolytes
      (AF) was used as the base solution to prepare test solutions (LAF, AFV, and LAFV)
      containing LE, MV, or both. Specifically, 20% LE was added to AF in a ratio of
      1:9 to prepare LAF. MV was added to AF and LAF to prepare AFV and LAFV,
      respectively. A specified number of each microorganism was added to each 100 mL
      of AF, LAF, AFV, and LAFV in sterile plastic flasks, and all flasks were allowed
      to stand at room temperature. The number of colony forming units per mL of each
      microorganism was counted at 0, 24, and 48 hours after the addition of each
      microorganism. RESULTS: Both Bacillus cereus and Serratia marcescens increased
      rapidly in AF as well as in LAF, AFV, and LAFV. Staphylococcus aureus did not
      increased in AF, but increased slightly in LAF and increased rapidly in AFV and
      LAFV. Candida albicans increased slightly in AF and increased rapidly in LAF,
      AFV, and LAFV. CONCLUSIONS: The results suggest the followings: if microbial
      contamination occurs, 1) Bacillus cereus and Serratia marcescens can grow rapidly
      in PPN solutions consisting of amino acids, glucose and electrolytes; 2)
      Staphylococcus aureus cannot grow without LE and MV, but can grow rapidly with
      MV; 3) Candida albicans can grow slowly without LE and MV, and the addition of LE
      or MV accelerates its growth.

PMID- 23869183
TI  - Utility and stability of transnasal endoscopy for examination of the pharynx - a
      prospective study and comparison with transoral endoscopy.
AB  - OBJECTIVE: Transnasal endoscopy may be used to observe the head and neck part
      readily without excessive reflexes. We aimed to evaluate the utility and
      stability of transnasal esophagogastroduodenoscopy (TN-EGD) in comparison with
      transoral EGD (TO-EGD) for observation of the pharynx. STUDY DESIGN: Prospective
      study METHODS: A total of 497 patients received unsedated TN-EGD with a 5.5 mm
      diameter endoscope or unsedated TO-EGD with endoscopes of 6.5 mm, 7.9 mm and 9.2
      mm diameter. The rate of completion of pharyngeal observation and numbers of gag
      reflexes and cough reflexes were recorded. RESULTS: TN-EGD was performed in 175
      patients and TO-EGD was performed in 322 patients. Pharyngeal observation was
      completed in 173 patients (98.9%) in the TN-EGD group and 235 patients (73.2%) in
      the TO-EGD group, a significant difference (p<0.001). The TN-EGD group had a low
      rate of occurrence of gag reflex (0.57%), in contrast, 28.3% of the TO-EGD group
      had a gag reflex, a significant difference (p<0.01). Multivariable analyses
      revealed that the use of TN-EGD was the only predictive factor for completion of
      pharyngeal observation (p<0.0001). CONCLUSIONS: TN-EGD is ideally suited to
      observation of the pharynx by unsedated EGD.

PMID- 23869184
TI  - Citrobacter peritoneal dialysis peritonitis: rare occurrence with poor outcomes.
AB  - INTRODUCTION: Non-Pseudomonas gram-negative bacteria are responsible for an
      increasing proportion of cases of peritoneal dialysis (PD)-related peritonitis.
      The role of Citrobacter species in the etiology of PD-related peritonitis is
      often underestimated. In the present study, we aimed to describe the clinical
      features, laboratory findings, and short- and long-term outcomes in PD-related
      peritonitis caused by Citrobacter. METHODS: A retrospective review of all
      episodes of PD-related peritonitis caused by Citrobacter from a single center
      between 1990 and 2010 was performed. Clinical features, microbiological data, and
      outcomes of these episodes were analyzed. RESULTS: Citrobacter species was
      responsible for 11 PD-related episodes (1.8% of all peritonitis episodes) in 8
      patients. Citrobacter freundii was the most common etiologic species (73%), and
      mixed growth was found in the other 3 episodes (27%). Approximately half (46%) of
      the episodes were associated with constipation and/or diarrhea. Of the
      Citrobacter isolates from all episodes, 54% were resistant to cefazolin, and only
      18% were susceptible to cefmetazole. All isolates were susceptible to
      ceftazidime, cefepime, carbapenem, and aminoglycosides. More than half of the
      patients (54%) were hospitalized for index peritonitis, and 27% of the episodes
      involved a change in antibiotic medication. One patient had relapsing peritonitis
      caused by C. koseri (9%). The mortality rate of PD-related peritonitis caused by
      Citrobacter was 18%, and 89% of surviving patients developed technique failure
      requiring a modality switch after an average of 12 months of follow-up (range 1.2
      31.2 months). CONCLUSION: PD-related peritonitis caused by Citrobacter is
      associated with poor outcomes, including high rates of antibiotic resistance, a
      high mortality rate, and a high rate of technique failure among survivors during
      the follow-up period.

PMID- 23869186
TI  - The importance of needle echogenity in ultrasound guided axillary brachial plexus
      block: a randomized controlled clinical study.
AB  - OBJECTIVE: In this study we aimed to compare the echogenic needles and the nerve
      stimulation addition to non-echogenic needles in ultrasound guided axillary
      brachial plexus block for upper extremity surgery. METHODS: 90 patients were
      enrolled to the study. The patients were allocated into three groups randomly:
      Group E (n=30): ultrasound guided axillary block using echogenic needle, Group N
      (n=30): ultrasound guided axillary block using non-echogenic needle, Group NS
      (n=30): ultrasound guided axillary block using non-echogenic needle with nerve
      stimulator assistance. Duration of block procedure, mean arterial pressure, heart
      rate, pulse-oximetry, onset time of sensory and motor block, duration of sensory
      and motor block, time to first analgesic use, total need for analgesics,
      postoperative pain scores, patient and surgeon satisfaction scores were recorded.
      RESULTS: Duration of block procedure values were lower in group E and NS, sensory
      and motor block durations, were significantly lower in group N. Sensorial and
      motor block onset time values were found lower in group NS but higher in group N.
      Patient and surgeon satisfaction scores were found lower in group N. CONCLUSION:
      We conclude that ultrasound guided axillary block may be performed successfully
      using both echogenic needles and nerve stimulation assisted non-echogenic
      needles.

PMID- 23869185
TI  - The effect of intraoperative use of high-dose remifentanil on postoperative
      insulin resistance and muscle protein catabolism: a randomized controlled study.
AB  - OBJECTIVE: We investigated the effect of the intraoperative use of a high dose
      remifentanil on insulin resistance and muscle protein catabolism. DESIGN:
      Randomized controlled study. PATIENTS AND INTERVENTION: Thirty-seven patients
      undergoing elective gastrectomy were randomly assigned to 2 groups that received
      remifentanil at infusion rates of 0.1 MUg.kg(-1).min(-1) (Group L) and 0.5
      MUg.kg(-1).min(-1) (Group H). MAIN OUTCOME MEASURES: Primary efficacy parameters
      were changes in homeostasis model assessment as an index of insulin resistance
      (HOMA-IR) and 3-methylhistidine/creatinine (3-MH/Cr). HOMA-IR was used to
      evaluate insulin resistance, and 3-MH/Cr was used to evaluate the progress of
      muscle protein catabolism. Intraoperative stress hormones, insulin, and blood
      glucose were assessed as secondary endpoints. RESULTS: Eighteen patients in Group
      L and 19 in Group H were examined. HOMA-IR values varied within normal limits in
      both groups during surgery, exceeding normal limits at 12 h after surgery and
      being significantly elevated in Group L. There were no significant differences in
      the 3-MH/Cr values between the 2 groups at any time point. The stress hormones
      (adrenocorticotropic hormone, cortisol, and adrenaline) were significantly
      elevated in Group L at 60 min after the start of surgery and at the initiation of
      skin closure. There were no significant differences in insulin values, but blood
      glucose was significantly elevated in Group L at 60 min after the start of
      surgery and at the start of skin closure. CONCLUSION: Use of high-dose
      remifentanil as intraoperative analgesia during elective gastrectomy reduced
      postoperative insulin resistance, although it did not reduce postoperative muscle
      protein catabolism.

PMID- 23869187
TI  - Meta-analysis of adiponectin polymorphisms and colorectal cancer risk.
AB  - OBJECTIVE: The adiponectin gene (ADIPOQ) has been suggested to be associated with
      the pathogenesis of colorectal cancer (CRC). However, the results have been
      inconsistent. In this study, we performed a meta-analysis to investigate the
      association between adiponectin polymorphisms and CRC risk. METHODS: All eligible
      case-control studies published up to March 2013 were identified by searching
      PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95%
      confidence interval (95% CI) were calculated by using a fixed- or random-effect
      model. RESULTS: A total of 9 case-control studies were included, Of those
      studies, there were eight studies (2024 cases and 2777 controls) for rs1501299G/T
      polymorphism, five studies (1401 cases and 1691 controls) for rs2241766T/G
      polymorphism, five studies (2945 cases and 3361 controls) for rs266729C/G
      polymorphism, three studies (1221 cases and 1579 controls) for rs822395A/C
      polymorphism and three studies (1222 cases and 1575 controls) for rs822396A/G
      polymorphism. Overall, a significant association was observed for rs2241766T/G
      polymorphism under heterozygote comparison (TG vs. TT: OR=1.22, 95%CI: 1.05
      1.43); while there was no significant association for rs2241766 polymorphism
      under other genetic models, and for other four polymorphisms under all genetic
      models. Besides, when stratified analyses by ethnicity, no significant
      association between five polymorphisms and CRC risk were observed under all
      genetic models among Asian, Caucasian and African-American. CONCLUSIONS: This
      meta-analysis indicated that adiponectin rs2241766T/G rather than rs1501299G/T,
      rs266729C/G, rs822395A/C and rs822396A/G polymorphism was associated with the
      risk of colorectal cancer.

PMID- 23869188
TI  - In-vivo functional study on the involvement of CFTR, SLC26A6, NHE-1 and CA
      isoenzymes II and XII in uterine fluid pH, volume and electrolyte regulation in
      rats under different sex-steroid influence.
AB  - Precise control of uterine fluid pH, volume and electrolytes is important for the
      reproductive processes. In this study, we examined the functional involvement of
      multiple proteins including Cystic Fibrosis Transmembrane Regulator (CFTR), Cl(
      )/HCO3 (-) exchanger (SLC26A6), sodium-hydrogen exchanger-1 (NHE-1) and carbonic
      anhydrase (CA) in the regulation of these uterine fluid parameters. METHODS:
      Adult female WKY rats were divided into intact, non-ovariectomised at different
      oestrous cycle phases and ovariectomised treated with sex-steroids. Following
      oestrous phase identification or sex-steroid treatment, in-vivo uterine perfusion
      was performed with and without the presence of these inhibitors: glibenclamide,
      DIDS, ACTZ and EIPA. The pH, volume, Cl(-), HCO3 (-) and Na(+) concentrations of
      the perfusate from different groups were then analyzed. Meanwhile, the expression
      of CFTR, SLC26A6, NHE-1, CAII and CAXII was visualized by immunohistochemistry
      (IHC). RESULTS: Parallel increase in the pH, volume, Cl(-), HCO3 (-) and Na(+)
      concentrations was observed at estrus (Es), proestrus (Ps) and following 17beta
      oestradiol (E) treatment, which was inhibited by glibenclamide, DIDS and ACTZ
      while parallel reduction in these parameters was observed at diestrus (Ds) and
      following progesterone (P) treatment which was inhibited by ACTZ and EIPA. CFTR
      and SLC26A6 expression were up-regulated under E dominance, while NHE-1
      expression was up-regulated under P dominance. Meanwhile, CA isoenzymes were
      expressed under both E and P influence. CONCLUSION: CFTR, SLC26A6 and CA were
      involved in mediating parallel increase in the uterine fluid volume, pH and
      electrolyte concentration under E while NHE and CA were involved in mediating the
      reduction of these parameters under P.

PMID- 23869190
TI  - Spatial localization of genes determined by intranuclear DNA fragmentation with
      the fusion proteins lamin KRED and histone KRED und visible light.
AB  - The highly organized DNA architecture inside of the nuclei of cells is accepted
      in the scientific world. In the human genome about 3 billion nucleotides are
      organized as chromatin in the cell nucleus. In general, they are involved in gene
      regulation and transcription by histone modification. Small chromosomes are
      localized in a central nuclear position whereas the large chromosomes are
      peripherally positioned. In our experiments we inserted fusion proteins
      consisting of a component of the nuclear lamina (lamin B1) and also histone H2A,
      both combined with the light inducible fluorescence protein KillerRed (KRED).
      After activation, KRED generates reactive oxygen species (ROS) producing toxic
      effects and may cause cell death. We analyzed the spatial damage distribution in
      the chromatin after illumination of the cells with visible light. The extent of
      DNA damage was strongly dependent on its localization inside of nuclei. The ROS
      activity allowed to gain information about the location of genes and their
      functions via sequencing and data base analysis of the double strand breaks of
      the isolated DNA. A connection between the damaged gene sequences and some
      diseases was found. 

PMID- 23869191
TI  - Dracorhodin perchlorate induced human breast cancer MCF-7 apoptosis through
      mitochondrial pathways.
AB  - OBJECTIVE: Dracorhodin perchlorate (DP) was a synthetic analogue of the
      antimicrobial anthocyanin red pigment dracorhodin. It was reported that DP could
      induce apoptosis in human prostate cancer, human gastric tumor cells and human
      melanoma, but the cytotoxic effect of DP on human breast cancer was not
      investigated. This study would investigate whether DP was a candidate chemical of
      anti-human breast cancer. METHODS: The MTT assay reflected the number of viable
      cells through measuring the activity of cellular enzymes. Phase contrast
      microscopy visualized cell morphology. Fluorescence microscopy detected nuclear
      fragmentation after Hoechst 33258 staining. Flowcytometric analysis of Annexin V
      PI staining and Rodamine 123 staining was used to detect cell apoptosis and
      mitochondrial membrane potential (MMP). Real time PCR detected mRNA level.
      Western blot examined protein expression. RESULTS: DP dose and time-dependently
      inhibited the growth of MCF-7 cells. DP inhibited MCF-7 cell growth through
      apoptosis. DP regulated the expression of Bcl-2 and Bax, which were mitochondrial
      pathway proteins, to decrease MMP, and DP promoted the transcription of Bax and
      inhibited Bcl-2. Apoptosis-inducing factor (AIF) and cytochrome c which localized
      in mitochondrial in physiological condition were released into cytoplasm when MMP
      was decreased. DP activated caspase-9, which was the downstream of mitochondrial
      pathway. Therefore DP decreased MMP to release AIF and cytochrome c into
      cytoplasm, further activating caspase 9, lastly led to apoptosis. CONCLUSION:
      Therefore DP was a candidate for anti-breast cancer, DP induced apoptosis of MCF
      7 through mitochondrial pathway.

PMID- 23869192
TI  - Designer cytokine hyper interleukin 11 (H11) is a megakaryopoietic factor.
AB  - Interleukin-11 (IL-11) displays megakaryopoietic activity. We constructed super
      cytokine Hyper- IL11 (H11) by linking soluble IL-11 receptor alpha (sIL-11Ralpha)
      with IL-11, which directly targets beta-receptor (gp130) signal transducing
      subunit. The effects of H11 on hematopoiesis with a focus on megakaryopoiesis
      were studied. The expansion, differentiation and type of colony formation of cord
      blood progenitor Lin-CD34+ cells were analyzed. H11 was more effective than
      recombinant human IL-11 (rhIL-11) in enhancement of the Lin-CD34+ cells expansion
      and differentiation into megakaryocytes (Mk). It induced higher expression of
      CD41a and CD61 antigens, resulting in a substantially larger population of CD34
      CD41a(high)CD61(high) cells. H11 treatment led to increased number of small and
      mainly medium megakaryocyte colony formation (Mk-CFU). Moreover, it induced the
      formation of a small number of large colonies, which were not observed following
      rhIL-11 treatment. Significantly higher number of H11 derived Mk colonies
      released platelets-like particles (PLP). Furthermore, H11 was considerably more
      potent than rhIL-11 in promoting differentiation of Lin-CD43+ cells toward
      erythrocytes. Our results indicate that H11 is more effective than rhIL-11 in
      enhancing expansion of early progenitors and directing them to megakaryocyte and
      erythroid cells and in inducing maturation of Mk. Thus, H11 may prove beneficial
      for thrombocytopenia treatment and/or an ex vivo expansion of megakaryocytes. 

PMID- 23869193
TI  - Survival, classifications, and desmosomal plaque genes in non-small cell lung
      cancer.
AB  - Novel biomarkers are required to improve prognostic predictions obtained with
      lung cancer staging systems. This study of 62 surgically-treated Non-Small Cell
      Lung Cancer (NSCLC) patients had two objectives: i) to compare the predictive
      value of T-stage classifications between the 6(th) and 7(th) editions of the
      Tumor, Node, and Metastasis staging system (TNM); and ii) to examine the
      association of Pkp1 and/or Krt15 gene expression with survival and outcomes.
      Multivariate and Kaplan-Meier survival analyses were performed, examining the
      relationship of survival with T-stage, recurrence, and TNM-stage (by each TNM
      edition) and with the single/combined expression of Pkp1 and/or Krt15 genes. Five
      year survival rates only significantly differed as a function of T-stage in
      patients without recurrence when estimated using the 6(th) edition of the TNM
      classification and only in patients in pathologic TNM-stage IA using the 7(th).
      Overall survival for patients with elevated expression of both genes was 13.5
      months in those with adenocarcinoma and 34.6 months in those with squamous cell
      carcinoma. Overall survival was 30.4 months in patients with Pkp1 gene
      upregulation and 30.9 months in those with Krt15 gene upregulation. In
      conclusion, survival estimations as a function of T-staging differed between the
      6(th) and 7(th) editions of TNM. Overall survival differed according to the
      expression of Pkp1 and/or Krt15 genes, although this relationship did not reach
      statistical significance. 

PMID- 23869194
TI  - Cognitive and emotional factors affecting avoidable decision-making delay in
      acute myocardial infarction male adults.
AB  - BACKGROUND: To study the potentially avoidable decision-making delay in acute
      myocardial infarction (AMI) adults male with different psychological
      characteristics a nationwide multicentre study was conducted in Italy by the 118
      Coronary Care Units (CCUs). METHOD: 929 AMI patients consecutively presented to
      the CCU in a conscious condition less than two hours, 2-6 hours, 6-12 hours, and
      more than 12 hours after symptom onset and completing the Disease Distress
      Questionnaire (DDQ) were enrolled in a multicentre case-control study. The DDQ
      collects information regarding the decision time to seek help, and includes a set
      of items assessing psychological factors and pain-related symptoms. The
      relationship between the perceived threat and the delay due to decision-making
      was evaluated by means of a multivariate model using LISREL 8 structural equation
      modelling. RESULTS: The delay significantly correlated with perceived threat,
      which was mainly related to somatic awareness. It was only slightly related to
      pain and was not associated with any of the other variables. Perceived threat was
      also related to psychological upset, fear and health worries, the first of which
      was considerably influenced by emotional instability. CONCLUSION: Somatic
      awareness is the main dimension affecting perceived threat, but subjective pain
      intensity affects the delay both directly and indirectly. The core of the model
      is the relationship between perceived threat and the delay due to decision
      making. The importance of subjective pain intensity is well documented, but it is
      still not clear how subjective and objective pain interact.

PMID- 23869195
TI  - Biomolecular membrane protein crystallization.
AB  - Integral membrane proteins comprise approximately 30% of the sequenced genomes,
      and there is an immediate need for their high-resolution structural information.
      Currently, the most reliable approach to obtain these structures is x-ray
      crystallography. However, obtaining crystals of membrane proteins that diffract
      to high resolution appears to be quite challenging, and remains a major obstacle
      in structural determination. This brief review summarizes a variety of
      methodologies for use in crystallizing these membrane proteins. Hopefully, by
      introducing the available methods, techniques, and providing a general
      understanding of membrane proteins, a rational decision can be made about now to
      crystallize these complex materials.

PMID- 23869196
TI  - Increased focus on the mouth among infants in the first year of life: A
      longitudinal eye-tracking study.
AB  - The present study examines face-scanning behaviors of infants at 6, 9, and 12
      months as they watched videos of a woman describing an object in front of her.
      The videos were created to vary information in the mouth (speaking vs. smiling)
      and the eyes (gazing into the camera vs. cueing the infant with head turn or gaze
      direction to an object being described). Infants tended to divide their attention
      between the eyes and the mouth, looking less at the eyes with age and more at the
      mouth than the eyes at 9 and 12 months. Attention to the mouth was greater on
      speaking trials than on smiling trials at all three ages, and this difference
      increased between 6 and 9 months. Despite consistent results within subjects,
      there was considerable variation between subjects. This raises the question of
      whether a developmental "norm" of face scanning in infancy ought to be pursued.
      Rather, these data add to emerging evidence suggesting that individual
      differences in face scanning might reliably predict aspects of later development.

PMID- 23869197
TI  - Microbial Translocation and B Cell Dysfunction in Human Immunodeficiency Virus
      Disease.
AB  - The gut mucosal barrier disrupted in HIV disease, resulting in increased systemic
      exposure to microbial products such as Lipo Polys Accharide (LPS). The
      association of enhanced microbial translocation and B cell dysfunction in HIV
      disease is not fully understood. High dose and short term exposure of microbial
      Toll-Like Receptor (TLR) agonists were used as vaccine adjuvants, however, low
      dose and long term exposure of TLR agonists could be harmful. The characteristics
      of B cell dysfunction in HIV disease included B cell, especially memory B cell
      depletion, enhanced levels of autoimmune antibodies and impaired vaccine or
      antigen responsiveness. This review discusses and explores the possibility of the
      effect of microbial translocation on memory B cell depletion and impaired vaccine
      responses in HIV infection. By determining the mechanisms of B cell depletion and
      perturbations in HIV disease, it may be possible to design interventions that can
      improve immune responses to vaccines, reduce selected opportunistic infections
      and perhaps slow disease progression.

PMID- 23869198
TI  - Using large-scale molecular data sets to improve breast cancer treatment.
AB  - The treatment of breast cancer patients could potentially be advanced by having a
      more complete understanding of breast cancer biology, including a catalog of
      recurrently altered genes. Over the last decade, thousands of human breast tumors
      have been profiled for gene expression and DNA copy number alterations, and
      ongoing efforts in DNA sequencing are establishing the set of somatically mutated
      genes. Much of the molecular data being generated resides in the public domain,
      available as a resource for further research. The challenge then becomes how to
      best utilize all these data, to mine them for candidate biomarkers and targets,
      which is the subject of this review. Some examples of integrative analysis and
      combining results from diverse data sets are also presented.

PMID- 23869199
TI  - PROBING THE IMPACT OF GAMMA-IRRADIATION ON THE METABOLIC STATE OF NEURAL STEM AND
      PRECURSOR CELLS USING DUAL-WAVELENGTH INTRINSIC SIGNAL TWO-PHOTON EXCITED
      FLUORESCENCE.
AB  - Two-photon excited fluorescence (TPEF) spectroscopy and imaging were used to
      investigate the effects of gamma-irradiation on neural stem and precursor cells
      (NSPCs). While the observed signal from reduced nicotinamide adenine dinucleotide
      (NADH) was localized to the mitochondria, the signal typically associated with
      oxidized flavoproteins (Fp) was distributed diffusely throughout the cell. The
      measured TPEF emission and excitation spectra were similar to the established
      spectra of NAD(P)H and Fp. Fp fluorescence intensity was markedly increased by
      addition of the electron transport chain (ETC) modulator menadione to the medium,
      along with a concomitant decrease in the NAD(P)H signal. Three-dimensional (3D)
      neurospheres were imaged to obtain the cellular metabolic index (CMI), calculated
      as the ratio of Fp to NAD(P)H fluorescence intensity. Radiation effects were
      found to differ between low-dose (<= 50 cGy) and high-dose (>= 50 cGy) exposures.
      Low-dose irradiation caused a marked drop in CMI values accompanied by increased
      cellular proliferation. At higher doses, both NAD(P)H and Fp signals increased,
      leading to an overall elevation in CMI values. These findings underscore the
      complex relationship between radiation dose, metabolic state, and proliferation
      status in NSPCs and highlight the ability of TPEF spectroscopy and imaging to
      characterize metabolism in 3D spheroids.

PMID- 23869200
TI  - Brain fingerprinting field studies comparing P300-MERMER and P300 brainwave
      responses in the detection of concealed information.
AB  - Brain fingerprinting detects concealed information stored in the brain by
      measuring brainwave responses. We compared P300 and P300-MERMER event-related
      brain potentials for error rate/accuracy and statistical confidence in four
      field/real-life studies. 76 tests detected presence or absence of information
      regarding (1) real-life events including felony crimes; (2) real crimes with
      substantial consequences (either a judicial outcome, i.e., evidence admitted in
      court, or a $100,000 reward for beating the test); (3) knowledge unique to FBI
      agents; and (4) knowledge unique to explosives (EOD/IED) experts. With both P300
      and P300-MERMER, error rate was 0 %: determinations were 100 % accurate, no false
      negatives or false positives; also no indeterminates. Countermeasures had no
      effect. Median statistical confidence for determinations was 99.9 % with P300
      MERMER and 99.6 % with P300. Brain fingerprinting methods and scientific
      standards for laboratory and field applications are discussed. Major differences
      in methods that produce different results are identified. Markedly different
      methods in other studies have produced over 10 times higher error rates and
      markedly lower statistical confidences than those of these, our previous studies,
      and independent replications. Data support the hypothesis that accuracy,
      reliability, and validity depend on following the brain fingerprinting scientific
      standards outlined herein. 

PMID- 23869201
TI  - On the Existence of Constant Accrual Rates in Clinical Trials and Direction for
      Future Research.
AB  - Many clinical trials fall short of their accrual goals. This can be avoided with
      accurate accrual prediction tools. Past researchers provide important
      methodological alternative models for predicting accrual in clinical trials. One
      model allows for slow accrual at the start of the study, which eventually reaches
      a threshold. A simpler model assumes a constant rate of accrual. A comparison has
      been attempted but we wish to point out some important considerations when
      comparing these two models. In fact, we can examine the reasonableness of a
      constant accrual assumption (simpler model) which had data 239 days into a three
      year study. We can now update that and report accumulated from the full three
      years of accrual data and we can demonstrate that constant accrual rate
      assumption was met in this particular study. We will use this report to frame
      future research in the area of accrual prediction.

PMID- 23869202
TI  - Glutamatergic dysbalance and oxidative stress in in vivo and in vitro models of
      psychosis based on chronic NMDA receptor antagonism.
AB  - BACKGROUND: The psychotomimetic effects of N-methyl-D-aspartate (NMDA) receptor
      antagonists in healthy humans and their tendency to aggravate psychotic symptoms
      in schizophrenic patients have promoted the notion of altered glutamatergic
      neurotransmission in the pathogenesis of schizophrenia. METHODS: The NMDA
      receptor antagonist MK-801 was chronically administered to rats (0.02 mg/kg
      intraperitoneally for 14 days). In one subgroup the antipsychotic haloperidol (1
      mg/kg) was employed as a rescue therapy. Glutamate distribution and 3-NT (3
      nitrotyrosine) as a marker of oxidative stress were assessed by
      immunohistochemistry in tissue sections. In parallel, the effects of MK-801 and
      haloperidol were investigated in primary embryonal hippocampal cell cultures from
      rats. RESULTS: Chronic NMDA-R antagonism led to a marked increase of
      intracellular glutamate in the hippocampus (126.1 +/- 10.4% S.E.M of control;
      p=0.037), while 3-NT staining intensity remained unaltered. No differences were
      observed in extrahippocampal brain regions. Essentially these findings could be
      reproduced in vitro. CONCLUSION: The combined in vivo and in vitro strategy
      allowed us to assess the implications of disturbed glutamate metabolism for the
      occurrence of oxidative stress and to investigate the effects of antipsychotics.
      Our data suggest that oxidative stress plays a minor role in this model than
      previously suggested. The same applies to apoptosis. Moreover, the effect of
      haloperidol seems to be mediated through yet unidentified mechanisms, unrelated
      to D2-antagonism. These convergent lines of evidence indicate that further
      research should be focused on the glutamatergic system and that our animal model
      may provide a tool to explore the biology of schizophrenia.

PMID- 23869203
TI  - Environmentally induced transgenerational epigenetic reprogramming of primordial
      germ cells and the subsequent germ line.
AB  - A number of environmental factors (e.g. toxicants) have been shown to promote the
      epigenetic transgenerational inheritance of disease and phenotypic variation.
      Transgenerational inheritance requires the germline transmission of altered
      epigenetic information between generations in the absence of direct environmental
      exposures. The primary periods for epigenetic programming of the germ line are
      those associated with primordial germ cell development and subsequent fetal
      germline development. The current study examined the actions of an agricultural
      fungicide vinclozolin on gestating female (F0 generation) progeny in regards to
      the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation
      (i.e. great-grandchildren). The F3 generation germline transcriptome and
      epigenome (DNA methylation) were altered transgenerationally. Interestingly,
      disruptions in DNA methylation patterns and altered transcriptomes were distinct
      between germ cells at the onset of gonadal sex determination at embryonic day 13
      (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger
      number of DNA methylation abnormalities (epimutations) and transcriptional
      alterations were observed in the E13 germ cells than in the E16 germ cells. These
      observations indicate that altered transgenerational epigenetic reprogramming and
      function of the male germline is a component of vinclozolin induced epigenetic
      transgenerational inheritance of disease. Insights into the molecular control of
      germline transmitted epigenetic inheritance are provided. 

PMID- 23869204
TI  - A standardized vascular disease health check in europe: a cost-effectiveness
      analysis.
AB  - BACKGROUND: No clinical trials have assessed the effects or cost-effectiveness of
      health check strategies to detect and manage vascular disease. We used a
      mathematical model to estimate the cost-effectiveness of several health check
      strategies in six European countries. METHODS: We used country-specific data from
      Denmark, France, Germany, Italy, Poland, and the United Kingdom to generate
      simulated populations of individuals aged 40-75 eligible for health checks in
      those countries (e.g. individuals without a previous diagnosis of diabetes,
      myocardial infarction, stroke, or serious chronic kidney disease). For each
      country, we used the Archimedes model to compare seven health check strategies
      consisting of assessments for diabetes, hypertension, lipids, and smoking. For
      patients diagnosed with vascular disease, treatment was simulated in a standard
      manner. We calculated the effects of each strategy on the incidence of type 2
      diabetes, major adverse cardiovascular events (MACE), and microvascular
      complications in addition to quality of life, costs, and cost per quality
      adjusted life-year (QALY). RESULTS: Compared with current care, health checks
      reduced the incidence of MACE (6-17 events prevented per 1000 people screened)
      and diabetes related microvasular complications (5-11 events prevented per 1000
      people screened), and increased QALYs (31-59 discounted QALYs) over 30 years, in
      all countries. The cost per QALY of offering a health check to all individuals in
      the study cohort ranged from ?14903 (France) to cost saving (Poland). Pre
      screening the population and offering health checks only to higher risk
      individuals lowered the cost per QALY. Pre-screening on the basis of obesity had
      a cost per QALY of ?10200 (France) or less, and pre-screening with a non-invasive
      risk score was similar. CONCLUSIONS: A vascular disease health check would likely
      be cost effective at 30 years in Denmark, France, Germany, Italy, Poland, and the
      United Kingdom.

PMID- 23869205
TI  - Insights into mechanisms and proteomic characterisation of Pseudomonas aeruginosa
      adaptation to a novel antimicrobial substance.
AB  - Antibiotic resistance has been reported since the introduction of synthetic
      antibiotics. Bacteria, such as one of the most common nosocomial pathogens P.
      aeruginosa, adapt quickly to changing environmental conditions, due to their
      short generation time. Thus microevolutional changes can be monitored in situ. In
      this study, the microevolutional process of Pseudomonas aeruginosa PAO1
      resistance against a recently developed novel antibacterial zinc Schiff-base
      (ZSB) was investigated at the proteome level. After extended exposure to ZSB the
      passaged strain differed in tolerance against ZSB, with the adapted P. aeruginosa
      PAO1 exhibiting 1.6 times higher minimal inhibitory concentration. Using Two
      dimensional Difference Gel Electrophoresis, the changes in the proteome of ZSB
      adapted P. aeruginosa PAO1 were examined by comparison with the non-adapted P.
      aeruginosa PAO1. The proteome of the adapted P. aeruginosa PAO1 strain differed
      significantly from the non-adapted in the abundance of two proteins when both
      strains were grown under stressing conditions. One protein could be identified as
      the outer membrane protein D that plays a role in uptake of basic amino acids as
      well as in carbapeneme resistance. The second protein has been identified as
      alkyl peroxide reductase subunit F. Our data indicated a slight increase in
      abundance of alkyl peroxide reductase F (AhpF) in the case of ZSB passaged P.
      aeruginosa PAO1. Higher abundance of Ahp has been discussed in the literature as
      a promoter of accelerated detoxification of benzene derivatives. The observed up
      regulated AhpF thus appears to be connected to an increased tolerance against
      ZSB. Changes in the abundance of proteins connected to oxidative stress were also
      found after short-time exposure of P. aeruginosa PAO1 to the ZSB. Furthermore,
      adapted P. aeruginosa PAO1 showed increased tolerance against hydrogen peroxide
      and, in addition, showed accelerated degradation of ZSB, as determined by HPLC
      measurements. 

PMID- 23869207
TI  - Computer simulation of assembly and co-operativity of hexameric AAA ATPases.
AB  - AAA ATPases form a functionally diverse superfamily of proteins. Most members
      form homo-hexameric ring complexes, are catalytically active only in the fully
      assembled state, and show co-operativity among the six subunits. The mutual
      dependence among the subunits is clearly evidenced by the fact that incorporation
      of mutated, inactive subunits can decrease the activity of the remaining wild
      type subunits. For the first time, we develop here models to describe this form
      of allostery, evaluate them in a simulation study, and test them on experimental
      data. We show that it is important to consider the assembly reactions in the
      kinetic model, and to define a formal inhibition scheme. We simulate three
      inhibition scenarios explicitly, and demonstrate that they result in differing
      outcomes. Finally, we deduce fitting formulas, and test them on real and
      simulated data. A non-competitive inhibition formula fitted experimental and
      simulated data best. To our knowledge, our study is the first one that derives
      and tests formal allosteric schemes to explain the inhibitory effects of mutant
      subunits on oligomeric enzymes. 

PMID- 23869206
TI  - Adding diverse noncanonical backbones to rosetta: enabling peptidomimetic design.
AB  - Peptidomimetics are classes of molecules that mimic structural and functional
      attributes of polypeptides. Peptidomimetic oligomers can frequently be
      synthesized using efficient solid phase synthesis procedures similar to peptide
      synthesis. Conformationally ordered peptidomimetic oligomers are finding broad
      applications for molecular recognition and for inhibiting protein-protein
      interactions. One critical limitation is the limited set of design tools for
      identifying oligomer sequences that can adopt desired conformations. Here, we
      present expansions to the ROSETTA platform that enable structure prediction and
      design of five non-peptidic oligomer scaffolds (noncanonical backbones),
      oligooxopiperazines, oligo-peptoids, [Formula: see text]-peptides, hydrogen bond
      surrogate helices and oligosaccharides. This work is complementary to prior
      additions to model noncanonical protein side chains in ROSETTA. The main purpose
      of our manuscript is to give a detailed description to current and future
      developers of how each of these noncanonical backbones was implemented.
      Furthermore, we provide a general outline for implementation of new backbone
      types not discussed here. To illustrate the utility of this approach, we describe
      the first tests of the ROSETTA molecular mechanics energy function in the context
      of oligooxopiperazines, using quantum mechanical calculations as comparison
      points, scanning through backbone and side chain torsion angles for a model
      peptidomimetic. Finally, as an example of a novel design application, we describe
      the automated design of an oligooxopiperazine that inhibits the p53-MDM2 protein
      protein interaction. For the general biological and bioengineering community,
      several noncanonical backbones have been incorporated into web applications that
      allow users to freely and rapidly test the presented protocols
      (http://rosie.rosettacommons.org). This work helps address the peptidomimetic
      community's need for an automated and expandable modeling tool for noncanonical
      backbones. 

PMID- 23869208
TI  - Macrophage subset sensitivity to endotoxin tolerisation by Porphyromonas
      gingivalis.
AB  - Macrophages (MPhis) determine oral mucosal responses; mediating tolerance to
      commensal microbes and food whilst maintaining the capacity to activate immune
      defences to pathogens. MPhi responses are determined by both differentiation and
      activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and
      anti-inflammatory/regulatory M2- MPhis. M2-like subsets predominate tolerance
      induction whereas M1 MPhis predominate in inflammatory pathologies, mediating
      destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG)
      periodontal infection. MPhi responses can be suppressed to benefit either the
      host or the pathogen. Chronic stimulation by bacterial pathogen associated
      molecular patterns (PAMPs), such as LPS, is well established to induce tolerance.
      The aim of this study was to investigate the susceptibility of MPhi subsets to
      suppression by P. gingivalis. CD14(hi) and CD14(lo) M1- and M2-like MPhis were
      generated in vitro from the THP-1 monocyte cell line by differentiation with PMA
      and vitamin D3, respectively. MPhi subsets were pre-treated with heat-killed PG
      (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of
      inflammation was measured by TNFalpha, IL-1beta, IL-6, IL-10 ELISA and NFkappaB
      activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP
      induced TNFalpha, IL-6 and IL-10 but fail to suppress IL-1beta expression in M1
      and M2 MPhis. In addition, P.gingivalis suppressed NFkappaB activation in
      CD14(lo) and CD14(hi) M2 regulatory MPhis and CD14(lo) M1 MPhis whereas CD14(hi)
      M1 pro-inflammatory MPhis were refractory to suppression. In conclusion,
      P.gingivalis selectively tolerises regulatory M2 MPhis with little effect on pro
      inflammatory CD14(hi) M1 MPhis; differential suppression facilitating
      immunopathology at the expense of immunity. 

PMID- 23869209
TI  - Arthropod phylogenetics in light of three novel millipede (myriapoda: diplopoda)
      mitochondrial genomes with comments on the appropriateness of mitochondrial
      genome sequence data for inferring deep level relationships.
AB  - BACKGROUND: Arthropods are the most diverse group of eukaryotic organisms, but
      their phylogenetic relationships are poorly understood. Herein, we describe three
      mitochondrial genomes representing orders of millipedes for which complete
      genomes had not been characterized. Newly sequenced genomes are combined with
      existing data to characterize the protein coding regions of myriapods and to
      attempt to reconstruct the evolutionary relationships within the Myriapoda and
      Arthropoda. RESULTS: The newly sequenced genomes are similar to previously
      characterized millipede sequences in terms of synteny and length. Unique
      translocations occurred within the newly sequenced taxa, including one half of
      the Appalachioria falcifera genome, which is inverted with respect to other
      millipede genomes. Across myriapods, amino acid conservation levels are highly
      dependent on the gene region. Additionally, individual loci varied in the level
      of amino acid conservation. Overall, most gene regions showed low levels of
      conservation at many sites. Attempts to reconstruct the evolutionary
      relationships suffered from questionable relationships and low support values.
      Analyses of phylogenetic informativeness show the lack of signal deep in the
      trees (i.e., genes evolve too quickly). As a result, the myriapod tree resembles
      previously published results but lacks convincing support, and, within the
      arthropod tree, well established groups were recovered as polyphyletic.
      CONCLUSIONS: The novel genome sequences described herein provide useful genomic
      information concerning millipede groups that had not been investigated. Taken
      together with existing sequences, the variety of compositions and evolution of
      myriapod mitochondrial genomes are shown to be more complex than previously
      thought. Unfortunately, the use of mitochondrial protein-coding regions in deep
      arthropod phylogenetics appears problematic, a result consistent with previously
      published studies. Lack of phylogenetic signal renders the resulting tree
      topologies as suspect. As such, these data are likely inappropriate for
      investigating such ancient relationships.

PMID- 23869210
TI  - Independent activity of the homologous small regulatory RNAs AbcR1 and AbcR2 in
      the legume symbiont Sinorhizobium meliloti.
AB  - The legume symbiont Sinorhizobium meliloti expresses a plethora of small
      noncoding RNAs (sRNAs) whose function is mostly unknown. Here, we have
      functionally characterized two tandemly encoded S. meliloti Rm1021 sRNAs that are
      similar in sequence and structure. Homologous sRNAs (designated AbcR1 and AbcR2)
      have been shown to regulate several ABC transporters in the related alpha
      proteobacteria Agrobacterium tumefaciens and Brucella abortus. In Rm1021, AbcR1
      and AbcR2 exhibit divergent unlinked regulation and are stabilized by the RNA
      chaperone Hfq. AbcR1 is transcribed in actively dividing bacteria, either in
      culture, rhizosphere or within the invasion zone of mature alfalfa nodules.
      Conversely, AbcR2 expression is induced upon entry into stationary phase and
      under abiotic stress. Only deletion of AbcR1 resulted into a discrete growth
      delay in rich medium, but both are dispensable for symbiosis. Periplasmic
      proteome profiling revealed down-regulation of the branched-chain amino acid
      binding protein LivK by AbcR1, but not by AbcR2. A double-plasmid reporter assay
      confirmed the predicted specific targeting of the 5'-untranslated region of the
      livK mRNA by AbcR1 in vivo. Our findings provide evidences of independent
      regulatory functions of these sRNAs, probably to fine-tune nutrient uptake in
      free-living and undifferentiated symbiotic rhizobia. 

PMID- 23869211
TI  - Distinct contributions of TNF receptor 1 and 2 to TNF-induced glomerular
      inflammation in mice.
AB  - TNF is an important mediator of glomerulonephritis. The two TNF-receptors TNFR1
      and TNFR2 contribute differently to glomerular inflammation in vivo, but specific
      mechanisms of TNFR-mediated inflammatory responses in glomeruli are unknown. We
      investigated their expression and function in murine kidneys, isolated glomeruli
      ex vivo, and glomerular cells in vitro. In normal kidney TNFR1 and TNFR2 were
      preferentially expressed in glomeruli. Expression of both TNFRs and TNF-induced
      upregulation of TNFR2 mRNA was confirmed in murine glomerular endothelial and
      mesangial cell lines. In vivo, TNF exposure rapidly induced glomerular
      accumulation of leukocytes. To examine TNFR-specific inflammatory responses in
      intrinsic glomerular cells but not infiltrating leukocytes we performed
      microarray gene expression profiling on intact glomeruli isolated from wildtype
      and Tnfr-deficient mice following exposure to soluble TNF ex vivo. Most TNF
      induced effects were exclusively mediated by TNFR1, including induced glomerular
      expression of adhesion molecules, chemokines, complement factors and pro
      apoptotic molecules. However, TNFR2 contributed to TNFR1-dependent mRNA
      expression of inflammatory mediators in glomeruli when exposed to low TNF
      concentrations. Chemokine secretion was absent in TNF-stimulated Tnfr1-deficient
      glomeruli, but also significantly decreased in glomeruli lacking TNFR2. In vivo,
      TNF-induced glomerular leukocyte infiltration was abrogated in Tnfr1-deficient
      mice, whereas Tnfr2-deficiency decreased mononuclear phagocytes infiltrates, but
      not neutrophils. These data demonstrate that activation of intrinsic glomerular
      cells by soluble TNF requires TNFR1, whereas TNFR2 is not essential, but augments
      TNFR1-dependent effects. Previously described TNFR2-dependent glomerular
      inflammation may therefore require TNFR2 activation by membrane-bound, but not
      soluble TNF. 

PMID- 23869212
TI  - Immune gene expression in Bombus terrestris: signatures of infection despite
      strong variation among populations, colonies, and sister workers.
AB  - Ecological immunology relies on variation in resistance to parasites. Colonies of
      the bumblebee Bombus terrestris vary in their susceptibility to the trypanosome
      gut parasite Crithidia bombi, which reduces colony fitness. To understand the
      possible origin of this variation in resistance we assayed the expression of 28
      immunologically important genes in foraging workers. We deliberately included
      natural variation of the host "environment" by using bees from colonies collected
      in two locations and sampling active foraging workers that were not age
      controlled. Immune gene expression patterns in response to C. bombi showed
      remarkable variability even among genetically similar sisters. Nevertheless,
      expression varied with parasite exposure, among colonies and, perhaps
      surprisingly, strongly among populations (collection sites). While only the
      antimicrobial peptide abaecin is universally up regulated upon exposure, linear
      discriminant analysis suggests that the overall exposure effect is driven by a
      combination of several immune pathways and further immune functions such as ROS
      regulation. Also, the differences among colonies in their immune gene expression
      profiles provide clues to the mechanistic basis of well-known inter-colony
      variation in susceptibility to this parasite. Our results show that
      transcriptional responses to parasite exposure can be detected in ecologically
      heterogeneous groups despite strong background noise. 

PMID- 23869213
TI  - Socioeconomic inequalities in non-communicable diseases prevalence in India:
      disparities between self-reported diagnoses and standardized measures.
AB  - BACKGROUND: Whether non-communicable diseases (NCDs) are diseases of poverty or
      affluence in low-and-middle income countries has been vigorously debated. Most
      analyses of NCDs have used self-reported data, which is biased by differential
      access to healthcare services between groups of different socioeconomic status
      (SES). We sought to compare self-reported diagnoses versus standardised measures
      of NCD prevalence across SES groups in India. METHODS: We calculated age-adjusted
      prevalence rates of common NCDs from the Study on Global Ageing and Adult Health,
      a nationally representative cross-sectional survey. We compared self-reported
      diagnoses to standardized measures of disease for five NCDs. We calculated wealth
      related and education-related disparities in NCD prevalence by calculating
      concentration index (C), which ranges from -1 to +1 (concentration of disease
      among lower and higher SES groups, respectively). FINDINGS: NCD prevalence was
      higher (range 5.2 to 19.1%) for standardised measures than self-reported
      diagnoses (range 3.1 to 9.4%). Several NCDs were particularly concentrated among
      higher SES groups according to self-reported diagnoses (Csrd) but were
      concentrated either among lower SES groups or showed no strong socioeconomic
      gradient using standardized measures (Csm): age-standardised wealth-related C:
      angina Csrd 0.02 vs. Csm -0.17; asthma and lung diseases Csrd -0.05 vs. Csm -0.04
      (age-standardised education-related Csrd 0.04 vs. Csm -0.05); vision problems
      Csrd 0.07 vs. Csm -0.05; depression Csrd 0.07 vs. Csm -0.13. Indicating similar
      trends of standardized measures detecting more cases among low SES, concentration
      of hypertension declined among higher SES (Csrd 0.19 vs. Csm 0.03). CONCLUSIONS:
      The socio-economic patterning of NCD prevalence differs markedly when assessed by
      standardized criteria versus self-reported diagnoses. NCDs in India are not
      necessarily diseases of affluence but also of poverty, indicating likely under
      diagnosis and under-reporting of diseases among the poor. Standardized measures
      should be used, wherever feasible, to estimate the true prevalence of NCDs.

PMID- 23869215
TI  - Geologic drivers of late ordovician faunal change in laurentia: investigating
      links between tectonics, speciation, and biotic invasions.
AB  - Geologic process, including tectonics and global climate change, profoundly
      impact the evolution of life because they have the propensity to facilitate
      episodes of biogeographic differentiation and influence patterns of speciation.
      We investigate causal links between a dramatic faunal turnover and two dominant
      geologic processes operating within Laurentia during the Late Ordovician: the
      Taconian Orogeny and GICE related global cooling. We utilize a novel approach for
      elucidating the relationship between biotic and geologic changes using a time
      stratigraphic, species-level evolutionary framework for articulated brachiopods
      from North America. Phylogenetic biogeographic analyses indicate a fundamental
      shift in speciation mode-from a vicariance to dispersal dominated
      macroevolutionary regime-across the boundary between the Sandbian to Katian
      Stages. This boundary also corresponds to the onset of renewed intensification of
      tectonic activity and mountain building, the development of an upwelling zone
      that introduced cool, nutrient-rich waters into the epieric seas of eastern
      Laurentia, and the GICE isotopic excursion. The synchronicity of these dramatic
      geologic, oceanographic, and macroevolutionary changes supports the influence of
      geologic events on biological evolution. Together, the renewed tectonic activity
      and oceanographic changes facilitated fundamental changes in habitat structure in
      eastern North America that reduced opportunities for isolation and vicariance.
      They also facilitated regional biotic dispersal of taxa that led to the
      subsequent establishment of extrabasinal (=invasive) species and may have led to
      a suppression of speciation within Laurentian faunas. Phylogenetic biogeographic
      analysis further indicates that the Richmondian Invasion was a multidirectional
      regional invasion event that involved taxa immigrating into the Cincinnati region
      from basins located near the continental margins and within the continental
      interior. 

PMID- 23869214
TI  - The alpha5 subunit regulates the expression and function of alpha4*-containing
      neuronal nicotinic acetylcholine receptors in the ventral-tegmental area.
AB  - Human genetic association studies have shown gene variants in the alpha5 subunit
      of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine
      dependence. The alpha5 subunit is an accessory subunit that facilitates alpha4*
      nAChRs assembly in vitro. However, it is unknown whether this occurs in the
      brain, as there are few research tools to adequately address this question. As
      the alpha4*-containing nAChRs are highly expressed in the ventral tegmental area
      (VTA) we assessed the molecular, functional and pharmacological roles of alpha5
      in alpha4*-containing nAChRs in the VTA. We utilized transgenic mice
      alpha5+/+(alpha4YFP) and alpha5-/-(alpha4YFP) that allow the direct visualization
      and measurement of alpha4-YFP expression and the effect of the presence
      (alpha5+/+) and absence of alpha5 (-/-) subunit, as the antibodies for detecting
      the alpha4* subunits of the nAChR are not specific. We performed voltage clamp
      electrophysiological experiments to study baseline nicotinic currents in VTA
      dopaminergic neurons. We show that in the presence of the alpha5 subunit, the
      overall expression of alpha4 subunit is increased significantly by 60% in the
      VTA. Furthermore, the alpha5 subunit strengthens baseline nAChR currents,
      suggesting the increased expression of alpha4* nAChRs to be likely on the cell
      surface. While the presence of the alpha5 subunit blunts the desensitization of
      nAChRs following nicotine exposure, it does not alter the amount of ethanol
      potentiation of VTA dopaminergic neurons. Our data demonstrates a major
      regulatory role for the alpha5 subunit in both the maintenance of alpha4*
      containing nAChRs expression and in modulating nicotinic currents in VTA
      dopaminergic neurons. Additionally, the alpha5alpha4* nAChR in VTA dopaminergic
      neurons regulates the effect of nicotine but not ethanol on currents. Together,
      the data suggest that the alpha5 subunit is critical for controlling the
      expression and functional role of a population of alpha4*-containing nAChRs in
      the VTA. 

PMID- 23869216
TI  - Characterization of free exopolysaccharides secreted by Mycoplasma mycoides
      subsp. mycoides.
AB  - Contagious bovine pleuropneumonia is a severe respiratory disease of cattle that
      is caused by a bacterium of the Mycoplasma genus, namely Mycoplasma mycoides
      subsp. mycoides (Mmm). In the absence of classical virulence determinants, the
      pathogenicity of Mmm is thought to rely on intrinsic metabolic functions and
      specific components of the outer cell surface. One of these latter, the capsular
      polysaccharide galactan has been notably demonstrated to play a role in Mmm
      persistence and dissemination. The free exopolysaccharides (EPS), also produced
      by Mmm and shown to circulate in the blood stream of infected cattle, have
      received little attention so far. Indeed, their characterization has been
      hindered by the presence of polysaccharide contaminants in the complex mycoplasma
      culture medium. In this study, we developed a method to produce large quantities
      of EPS by transfer of mycoplasma cells from their complex broth to a chemically
      defined medium and subsequent purification. NMR analyses revealed that the
      purified, free EPS had an identical beta(1->6)-galactofuranosyl structure to that
      of capsular galactan. We then analyzed intraclonal Mmm variants that produce
      opaque/translucent colonies on agar. First, we demonstrated that colony opacity
      was related to the production of a capsule, as observed by electron microscopy.
      We then compared the EPS extracts and showed that the non-capsulated, translucent
      colony variants produced higher amounts of free EPS than the capsulated, opaque
      colony variants. This phenotypic variation was associated with an antigenic
      variation of a specific glucose phosphotransferase permease. Finally, we
      conducted in silico analyses of candidate polysaccharide biosynthetic pathways in
      order to decipher the potential link between glucose phosphotransferase permease
      activity and attachment/release of galactan. The co-existence of variants
      producing alternative forms of galactan (capsular versus free extracellular
      galactan) and associated with an antigenic switch constitutes a finely tuned
      mechanism that may be involved in virulence. 

PMID- 23869217
TI  - Cooperative roles of SDF-1alpha and EGF gradients on tumor cell migration
      revealed by a robust 3D microfluidic model.
AB  - Chemokine-mediated directed tumor cell migration within a three dimensional (3D)
      matrix, or chemoinvasion, is an important early step in cancer metastasis.
      Despite its clinical importance, it is largely unknown how cytokine and growth
      factor gradients within the tumor microenvironment regulate chemoinvasion. We
      studied tumor cell chemoinvasion in well-defined and stable chemical gradients
      using a robust 3D microfluidic model. We used CXCL12 (also known as SDF-1alpha)
      and epidermal growth factor (EGF), two well-known extracellular signaling
      molecules that co-exist in the tumor microenvironment (e.g. lymph nodes or
      intravasation sites), and a malignant breast tumor cell line, MDA-MB-231,
      embedded in type I collagen. When subjected to SDF-1alpha gradients alone, MDA-MB
      231 cells migrated up the gradient, and the measured chemosensitivity (defined as
      the average cell velocity along the direction of the gradient) followed the
      ligand - receptor (SDF-1alpha - CXCR4) binding kinetics. On the other hand, when
      subjected to EGF gradients alone, tumor cells increased their overall motility,
      but without statistically significant chemotactic (directed) migration, in
      contrast to previous reports using 2D chemotaxis assays. Interestingly, we found
      that the chemoinvasive behavior to SDF-1alpha gradients was abrogated or even
      reversed in the presence of uniform concentrations of EGF; however, the presence
      of SDF-1alpha and EGF together modulated tumor cell motility cooperatively. These
      findings demonstrate the capabilities of our microfluidic model in re-creating
      complex microenvironments for cells, and the importance of cooperative roles of
      multiple cytokine and growth factor gradients in regulating cell migration in 3D
      environments. 

PMID- 23869218
TI  - Comparative assessment of cytokines and other inflammatory markers for the early
      diagnosis of neonatal sepsis-a case control study.
AB  - OBJECTIVE: Cytokines (IL-6, IL-8 and TNF-alpha), sCD163, and C-reactive protein
      were serially measured in an attempt to identify a set of tests which can
      reliably confirm or refute the diagnosis of neonatal sepsis at an early stage.
      METHODS: One hundred neonates suspected to have sepsis on clinical grounds and
      who met the inclusion criteria were enrolled for the study. Based on the positive
      or negative blood culture reports they were classified as infected (n=50) and non
      infected (n=50) neonates respectively. Fifty healthy neonates without any signs
      of sepsis were also included in the study as control group. The initial blood
      sample was taken on day 0 (at the time of sepsis evaluation) and two further
      samples were taken on days 1 and 2 for monitoring the clinical progress and
      response to treatment. In the control group the cord blood and 48 hours venous
      sample was collected. Plasma CRP (ng/ml), IL-6 (pg/ml), IL-8 (pg/ml), TNF-alpha
      (ng/ml) and sCD163 (ng/ml) were determined by double antibody method Enzyme
      Linked Immunosorbent Assay in all the three blood samples. RESULTS: The cut of
      levels for CRP at >19,689 ng/ml had a sensitivity of 68%, specificity of 92%, for
      IL-6 at >95.32 pg/ml had a sensitivity of 54%, specificity of 96%, for IL-8 at
      >70.86 pg/ml had a sensitivity of 78%, specificity of 70%, for sCD163 at >896.78
      ng/ml had a sensitivity of 100%, specificity of 88% for the diagnosis of
      infection before antibiotics. TNF-alpha levels of >12.6 ng/ml showed 100%
      sensitivity and 72% specificity for the diagnosis of inflammation. CONCLUSION:
      The most powerful predictor to differentiate between the non-infected and
      infected neonates before antibiotics was sCD163. The most powerful indicator for
      evaluation of prognosis is IL-6. sCD163 can be used alone to screen for sepsis in
      neonates before the results of blood culture are received.

PMID- 23869219
TI  - Summer rains and dry seasons in the upper Blue Nile Basin: the predictability of
      half a century of past and future spatiotemporal patterns.
AB  - During the last 100 years the Ethiopian upper Blue Nile Basin (BNB) has undergone
      major changes in land use, and is now potentially facing changes in climate.
      Rainfall over BNB supplies over two-thirds of the water to the Nile and supports
      a large local population living mainly on subsistence agriculture. Regional food
      security is sensitive to both the amount and timing of rain and is already an
      important political challenge that will be further complicated if scenarios of
      climate change are realized. In this study a simple spatial model of the timing
      and duration of summer rains (Kiremt) and dry season (Bega), and annual rain over
      the upper BNB was established from observed data between 1952 and 2004. The model
      was used to explore potential impacts of climate change on these rains, using a
      down-scaled ECHAM5/MP1-OM scenario between 2050 and 2100. Over the observed
      period the amount, onset and duration of Kiremt rains and rain-free Bega days
      have exhibited a consistent spatial pattern. The spatially averaged annual
      rainfall was 1490 mm of which 93% was Kiremt rain. The average Kiremt rain and
      number of rainy days was higher in the southwest (322 days) and decreased towards
      the north (136 days). Under the 2050-2100 scenario, the annual mean rainfall is
      predicted to increase by 6% and maintain the same spatial pattern as in the past.
      A larger change in annual rainfall is expected in the southwest (ca. +130 mm)
      with a gradually smaller change towards the north (ca. +70 mm). Results highlight
      the need to account for the characteristic spatiotemporal zonation when planning
      water management and climate adaptation within the upper BNB. The presented
      simple spatial resolved models of the presence of Kiremt and annual total
      rainfall could be used as a baseline for such long-term planning. 

PMID- 23869220
TI  - Incidence and characterisation of methicillin-resistant Staphylococcus aureus
      (MRSA) from nasal colonisation in participants attending a cattle veterinary
      conference in the UK.
AB  - We sought to determine the prevalence of nasal colonisation with methicillin
      resistant Staphylococcus aureus among cattle veterinarians in the UK. There was
      particular interest in examining the frequency of colonisation with MRSA
      harbouring mecC, as strains with this mecA homologue were originally identified
      in bovine milk and may represent a zoonotic risk to those in contact with dairy
      livestock. Three hundred and seven delegates at the British Cattle Veterinarian
      Association (BCVA) Congress 2011 in Southport, UK were screening for nasal
      colonisation with MRSA. Isolates were characterised by whole genome sequencing
      and antimicrobial susceptibility testing. Eight out of three hundred and seven
      delegates (2.6%) were positive for nasal colonisation with MRSA. All strains were
      positive for mecA and none possessed mecC. The time since a delegate's last visit
      to a farm was significantly shorter in the MRSA-positive group than in MRSA
      negative counterparts. BCVA delegates have an increased risk of MRSA colonisation
      compared to the general population but their frequency of colonisation is lower
      than that reported from other types of veterinarian conference, and from that
      seen in human healthcare workers. The results indicate that recent visitation to
      a farm is a risk factor for MRSA colonisation and that mecC-MRSA are rare among
      BCVA delegates (<1% based on sample size). Contact with livestock, including
      dairy cattle, may still be a risk factor for human colonisation with mecC-MRSA
      but occurs at a rate below the lower limit of detection available in this study. 

PMID- 23869221
TI  - An improved method for TAL effectors DNA-binding sites prediction reveals
      functional convergence in TAL repertoires of Xanthomonas oryzae strains.
AB  - Transcription Activators-Like Effectors (TALEs) belong to a family of virulence
      proteins from the Xanthomonas genus of bacterial plant pathogens that are
      translocated into the plant cell. In the nucleus, TALEs act as transcription
      factors inducing the expression of susceptibility genes. A code for TALE-DNA
      binding specificity and high-resolution three-dimensional structures of TALE-DNA
      complexes were recently reported. Accurate prediction of TAL Effector Binding
      Elements (EBEs) is essential to elucidate the biological functions of the many
      sequenced TALEs as well as for robust design of artificial TALE DNA-binding
      domains in biotechnological applications. In this work a program with improved
      EBE prediction performances was developed using an updated specificity matrix and
      a position weight correction function to account for the matching pattern
      observed in a validation set of TALE-DNA interactions. To gain a systems
      perspective on the large TALE repertoires from X. oryzae strains, this program
      was used to predict rice gene targets for 99 sequenced family members.
      Integrating predictions and available expression data in a TALE-gene network
      revealed multiple candidate transcriptional targets for many TALEs as well as
      several possible instances of functional convergence among TALEs. 

PMID- 23869222
TI  - MicroRNA-326 functions as a tumor suppressor in glioma by targeting the Nin one
      binding protein (NOB1).
AB  - Malignant glioma is the most common type of primary brain tumor in adults,
      characterized by rapid tumor growth and infiltration of tumor cells throughout
      the brain. Alterations in the activity of the 26S proteasome have been associated
      with malignant glioma cells, although the specific defects have not been
      identified. Recently, microRNA-326 (miR-326) was shown to play an important role
      in glioblastoma and breast cancer, but the underlying molecular mechanisms remain
      unclear. In the present study, the human Nin one binding protein (NOB1) was
      identified as a direct target of miR-326 and a potential oncogene in human
      glioma. Similar to NOB1 silencing by shRNA, overexpression of miR-326 in human
      glioma cell lines (A172 and U373) caused cell cycle arrest at the G1 phase,
      delayed cell proliferation and enhanced apoptosis. MiR-326 inhibited colony
      formation in soft agar and decreased growth of a xenograft tumor model,
      suggesting that miR-326 and NOB1 are required for tumorigenesis in vitro and in
      vivo. Furthermore, these processes were shown to involve the MAPK pathway. NOB1
      overexpression in human glioma samples was detected by Affymetrix array analysis,
      and NOB1 mRNA and protein levels were shown to be increased in high-grade glioma
      compared to low-grade glioma and normal brain tissue. Furthermore, high levels of
      NOB1 were associated with unfavorable prognosis of glioma patients. Taken
      together, these results indicate that miR-326 and NOB1 may play an important role
      in the development of glioma. 

PMID- 23869223
TI  - Evolution of plant HECT ubiquitin ligases.
AB  - HECT ubiquitin ligases are key components of the ubiquitin-proteasome system,
      which is present in all eukaryotes. In this study, the patterns of emergence of
      HECT genes in plants are described. Phylogenetic and structural data indicate
      that viridiplantae have six main HECT subfamilies, which arose before the split
      that separated green algae from the rest of plants. It is estimated that the
      common ancestor of all plants contained seven HECT genes. Contrary to what
      happened in animals, the number of HECT genes has been kept quite constant in all
      lineages, both in chlorophyta and streptophyta, although evolutionary recent
      duplications are found in some species. Several of the genes found in plants may
      have originated very early in eukaryotic evolution, given that they have clear
      similarities, both in sequence and structure, to animal genes. Finally, in
      Arabidopsis thaliana, we found significant correlations in the expression
      patterns of HECT genes and some ancient, broadly expressed genes that belong to a
      different ubiquitin ligase family, called RBR. These results are discussed in the
      context of the evolution of the gene families required for ubiquitination in
      plants. 

PMID- 23869224
TI  - Rupatadine protects against pulmonary fibrosis by attenuating PAF-mediated
      senescence in rodents.
AB  - A similar immune response is implicated in the pathogenesis of pulmonary fibrosis
      and allergic disorders. We investigated the potential therapeutic efficacy and
      mechanism of rupatadine, a dual antagonist of histamine and platelet-activation
      factor (PAF), in bleomycin- (BLM-) and silica-induced pulmonary fibrosis. The
      indicated dosages of rupatadine were administered in rodents with bleomycin or
      silica-induced pulmonary fibrosis. The tissue injury, fibrosis, inflammatory
      cells and cytokines, and lung function were examined to evaluate the therapeutic
      efficacy of rupatadine. The anti-fibrosis effect of rupatadine was compared with
      an H1 or PAF receptor antagonist, and efforts were made to reveal rupatadine's
      anti-fibrotic mechanism. Rupatadine promoted the resolution of pulmonary
      inflammation and fibrosis in a dose-dependent manner, as indicated by the
      reductions in inflammation score, collagen deposition and epithelial-mesenchymal
      transformation, and infiltration or expression of inflammatory cells or cytokines
      in the fibrotic lung tissue. Thus, rupatadine treatment improved the declined
      lung function and significantly decreased animal death. Moreover, rupatadine was
      able not only to attenuate silica-induced silicosis but also to produce a
      superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist
      loratadine, or PAF antagonist CV-3988. The anti-fibrotic action of rupatadine
      might relate to its attenuation of BLM- or PAF-induced premature senescence
      because rupatadine treatment protected against the in vivo and in vitro
      activation of the p53/p21-dependent senescence pathway. Our studies indicate that
      rupatadine promotes the resolution of pulmonary inflammation and fibrosis by
      attenuating the PAF-mediated senescence response. Rupatadine holds promise as a
      novel drug to treat the devastating disease of pulmonary fibrosis. 

PMID- 23869225
TI  - HIV-1 diversity, drug-resistant mutations, and viral evolution among high-risk
      individuals in phase II HIV vaccine trial sites in southern China.
AB  - HIV-1 prevalence in Guangxi, China, has been growing since 1996, when the first
      case was reported. Over half of HIV-1 positive patients in Guangxi Province were
      injecting drug users (IDUs), possibly because of the province's location near
      drug-trafficking routes. Since a phase II HIV vaccine trial is ongoing there, a
      current characterization of the subtypes of HIV-1 among IDUs in Guangxi would
      provide critical information for future HIV vaccine trials, as well as further
      control and prevention of HIV-1 transmission. Thus, we conducted a molecular
      epidemiological investigation of HIV-1 samples from 2008-2010 among IDUs in
      multiple cities in Guangxi Province. Our results, based on the gag/pol fragment,
      indicated a very high proportion (78.47%) of HIV-1 CRF08_BC recombinants, some
      CRF01_AE (15.38%) recombinants, and a low proportion of CRF07_BC (6.15%)
      recombinants among the IDUs. The high proportion of CRF08 HIV-1 strains among
      recent IDUs matches the vaccine candidate constructs. However, future vaccine
      development should also incorporate CRF01-targeted vaccine candidates. Distinct
      Env sequence evolution patterns were observed for CRF08_BC and CRF01_AE,
      indicating that different local selection pressures have been exerted on these
      two HIV-1 subtypes. Unique drug-resistant mutations were also detected, and our
      data indicate that HIV treatment programs should consider pre-existing drug
      resistant mutations. 

PMID- 23869226
TI  - High weight loss during radiation treatment changes the prognosis in under
      /normal weight nasopharyngeal carcinoma patients for the worse: a retrospective
      analysis of 2433 cases.
AB  - BACKGROUND: Although weight loss is common in nasopharyngeal carcinoma (NPC)
      patients receiving radiotherapy, the prognostic influence of weight loss and its
      impact modified by body mass index (BMI) are still unclear. METHODS: 2433 NPC
      patients receiving radical radiotherapy at Sun Yat-sen University Cancer Center
      from November, 2000 to December, 2004 were enrolled. Weight change during
      radiation treatment was categorized into high weight loss (HWL) and low weight
      loss (LWL). The associations of HWL with overall survival (OS) and disease
      specific survival (DSS) were analyzed by Cox regression. RESULTS: Among
      underweight patients, HWL was independently associated with poor OS (hazard ratio
      [HR], 2.06; 95% CI 1.36-3.11) and DSS (HR, 2.27; 95% CI 1.38-3.73), as compared
      with LWL, after adjusting for covariates. In normal weight patients, the impact
      of HWL on OS (HR, 1.47; 95% CI 1.19-1.80) and DSS (HR, 1.59; 95% CI 1.24-2.03)
      was moderate. Among overweight/obese patients, no significant association between
      HWL and OS (HR, 1.22; 95% CI 0.95-1.55), or DSS (HR, 1.23; 95% CI 0.93-1.64) was
      found. CONCLUSION: Except for overweight/obese patients, high weight loss during
      radiation treatment was independently associated with poor survival in NPC. This
      impact was more prominent in the underweight patient group.

PMID- 23869228
TI  - An inducible transgenic mouse model for immune mediated hepatitis showing
      clearance of antigen expressing hepatocytes by CD8+ T cells.
AB  - The liver has the ability to prime immune responses against neo antigens provided
      upon infections. However, T cell immunity in liver is uniquely modulated by the
      complex tolerogenic property of this organ that has to also cope with foreign
      agents such as endotoxins or food antigens. In this respect, the nature of
      intrahepatic T cell responses remains to be fully characterized. To gain deeper
      insight into the mechanisms that regulate the CD8+ T cell responses in the liver,
      we established a novel OVA_X_CreER(T2) mouse model. Upon tamoxifen administration
      OVA antigen expression is observed in a fraction of hepatocytes, resulting in a
      mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with
      antigen-expressing hepatocytes, we adoptively transferred K(b)/OVA257-264
      specific OT-I T cells to OVA_X_CreER(T2) mice or generated triple transgenic
      OVA_X CreER(T2)_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2)
      mice and induce an acute and transient hepatitis accompanied by liver damage. In
      OVA_X_CreER(T2)_X_OT-I mice, OVA induction triggers an OT-I T cell mediated,
      fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long
      lasting hepatitis, and recover after 9 weeks. In these experimental settings,
      recovery from hepatitis correlates with a complete loss of OVA expression
      indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a
      relapse of hepatitis can be induced upon re-induction of cured
      OVA_X_CreER(T2)_X_OT-I mice indicating absence of tolerogenic mechanisms. This
      pathogen-free, conditional mouse model has the advantage of tamoxifen inducible
      tissue specific antigen expression that reflects the heterogeneity of viral
      antigen expression and enables the study of intrahepatic immune responses to both
      de novo and persistent antigen. It allows following the course of intrahepatic
      immune responses: initiation, the acute phase and antigen clearance. 

PMID- 23869227
TI  - Multi-scale modeling predicts a balance of tumor necrosis factor-alpha and
      interleukin-10 controls the granuloma environment during Mycobacterium
      tuberculosis infection.
AB  - Interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha) are key anti-
      and pro-inflammatory mediators elicited during the host immune response to
      Mycobacterium tuberculosis (Mtb). Understanding the opposing effects of these
      mediators is difficult due to the complexity of processes acting across different
      spatial (molecular, cellular, and tissue) and temporal (seconds to years) scales.
      We take an in silico approach and use multi-scale agent based modeling of the
      immune response to Mtb, including molecular scale details for both TNF-alpha and
      IL-10. Our model predicts that IL-10 is necessary to modulate macrophage
      activation levels and to prevent host-induced tissue damage in a granuloma, an
      aggregate of cells that forms in response to Mtb. We show that TNF-alpha and IL
      10 parameters related to synthesis, signaling, and spatial distribution processes
      control concentrations of TNF-alpha and IL-10 in a granuloma and determine
      infection outcome in the long-term. We devise an overall measure of granuloma
      function based on three metrics - total bacterial load, macrophage activation
      levels, and apoptosis of resting macrophages - and use this metric to demonstrate
      a balance of TNF-alpha and IL-10 concentrations is essential to Mtb infection
      control, within a single granuloma, with minimal host-induced tissue damage. Our
      findings suggest that a balance of TNF-alpha and IL-10 defines a granuloma
      environment that may be beneficial for both host and pathogen, but perturbing the
      balance could be used as a novel therapeutic strategy to modulate infection
      outcomes. 

PMID- 23869229
TI  - Yeast "make-accumulate-consume" life strategy evolved as a multi-step process
      that predates the whole genome duplication.
AB  - When fruits ripen, microbial communities start a fierce competition for the
      freely available fruit sugars. Three yeast lineages, including baker's yeast
      Saccharomyces cerevisiae, have independently developed the metabolic activity to
      convert simple sugars into ethanol even under fully aerobic conditions. This
      fermentation capacity, named Crabtree effect, reduces the cell-biomass production
      but provides in nature a tool to out-compete other microorganisms. Here, we
      analyzed over forty Saccharomycetaceae yeasts, covering over 200 million years of
      the evolutionary history, for their carbon metabolism. The experiments were done
      under strictly controlled and uniform conditions, which has not been done before.
      We show that the origin of Crabtree effect in Saccharomycetaceae predates the
      whole genome duplication and became a settled metabolic trait after the split of
      the S. cerevisiae and Kluyveromyces lineages, and coincided with the origin of
      modern fruit bearing plants. Our results suggest that ethanol fermentation
      evolved progressively, involving several successive molecular events that have
      gradually remodeled the yeast carbon metabolism. While some of the final
      evolutionary events, like gene duplications of glucose transporters and
      glycolytic enzymes, have been deduced, the earliest molecular events initiating
      Crabtree effect are still to be determined. 

PMID- 23869230
TI  - Assessing the fecal microbiota: an optimized ion torrent 16S rRNA gene-based
      analysis protocol.
AB  - Assessing the distribution of 16S rRNA gene sequences within a biological sample
      represents the current state-of-the-art for determination of human gut microbiota
      composition. Advances in dissecting the microbial biodiversity of this ecosystem
      have very much been dependent on the development of novel high-throughput DNA
      sequencing technologies, like the Ion Torrent. However, the precise
      representation of this bacterial community may be affected by the protocols used
      for DNA extraction as well as by the PCR primers employed in the amplification
      reaction. Here, we describe an optimized protocol for 16S rRNA gene-based
      profiling of the fecal microbiota. 

PMID- 23869231
TI  - Whole genome SNP genotyping and exome sequencing reveal novel genetic variants
      and putative causative genes in congenital hyperinsulinism.
AB  - Congenital hyperinsulinism of infancy (CHI) is a rare disorder characterized by
      severe hypoglycemia due to inappropriate insulin secretion. The genetic causes of
      CHI have been found in genes regulating insulin secretion from pancreatic beta
      cells; recessive inactivating mutations in the ABCC8 and KCNJ11 genes represent
      the most common events. Despite the advances in understanding the molecular
      pathogenesis of CHI, specific genetic determinants in about 50 % of the CHI
      patients remain unknown, suggesting additional locus heterogeneity. In order to
      search for novel loci contributing to the pathogenesis of CHI, we combined a
      family-based association study, using the transmission disequilibrium test on 17
      CHI patients lacking mutations in ABCC8/KCNJ11, with a whole-exome sequencing
      analysis performed on 10 probands. This strategy allowed the identification of
      the potential causative mutations in genes implicated in the regulation of
      insulin secretion such as transmembrane proteins (CACNA1A, KCNH6, KCNJ10, NOTCH2,
      RYR3, SCN8A, TRPV3, TRPC5), cytosolic (ACACB, CAMK2D, CDKAL1, GNAS, NOS2, PDE4C,
      PIK3R3) and mitochondrial enzymes (PC, SLC24A6), and in four genes (CSMD1,
      SLC37A3, SULF1, TLL1) suggested by TDT family-based association study. Moreover,
      the exome-sequencing approach resulted to be an efficient diagnostic tool for
      CHI, allowing the identification of mutations in three causative CHI genes
      (ABCC8, GLUD1, and HNF1A) in four out of 10 patients. Overall, the present study
      should be considered as a starting point to design further investigations: our
      results might indeed contribute to meta-analysis studies, aimed at the
      identification/confirmation of novel causative or modifier genes. 

PMID- 23869233
TI  - Caffeine intake, short bouts of physical activity, and energy expenditure: a
      double-blind randomized crossover trial.
AB  - PA energy expenditure (PAEE) is the most variable component of Total Energy
      Expenditure (TEE) and largely due to the balance of sedentary time (SedT) and low
      intensity physical activity (LIPA). There has been an emergence for seeking an
      understanding of factors which determine variations in SedT, LIPA, and PAEE.
      Sedentary behavior and physical activity are relatively resistant to change by
      experimental dietary treatments and significant body weight changes. Although
      caffeine (Caf) is by far the most heavily used nutritional agent ingested to
      promote a sense of vigor/alertness, it is still unknown if Caf is effective in
      increasing PAEE and physical activity. The aim of the study was to test the
      hypothesis that 2 daily doses of Caf (as a capsule to blind the treatment and
      divided equally during breakfast and lunch) increase PAEE and TEE, and it would
      do so through increasing the frequent and brief bouts of physical activity (~1-5
      min long) through the day as measured by accelerometry. In 21 low Caf users (<100
      mg day(-1)), we used a double-blind crossover trial
      (ClinicalTrials.govID;NCT01477294) with two conditions (4-day each with a 3-day
      washout period) randomly ordered as 5 mg kg(-1) day(-1) of Caf and maltodextrin
      as placebo (Plc). Resting energy expenditure (REE) by indirect calorimetry, total
      energy expenditure (TEE) from doubly labeled water, PAEE calculated as TEE
      (REE+0.1TEE), and accelerometry measurements of both LIPA and MVPA were not
      different between conditions. However, regardless of caffeine or placebo, there
      were several significant relationships between brief bouts of LIPA and MVPA with
      PAEE. In conclusion, this double-blind study found that low and moderate-vigorous
      activity as well as the total volume of PAEE in free-living conditions is
      resistant to dietary caffeine intake that was equivalent to 5 cups of espresso or
      7 cups of tea. TRIAL REGISTRATION: ClinicalTrials.gov NCT01477294.

PMID- 23869232
TI  - Gastrointestinal cell lines form polarized epithelia with an adherent mucus layer
      when cultured in semi-wet interfaces with mechanical stimulation.
AB  - Mucin glycoproteins are secreted in large quantities by mucosal epithelia and
      cell surface mucins are a prominent feature of the glycocalyx of all mucosal
      epithelia. Currently, studies investigating the gastrointestinal mucosal barrier
      use either animal experiments or non-in vivo like cell cultures. Many pathogens
      cause different pathology in mice compared to humans and the in vitro cell
      cultures used are suboptimal because they are very different from an in vivo
      mucosal surface, are often not polarized, lack important components of the
      glycocalyx, and often lack the mucus layer. Although gastrointestinal cell lines
      exist that produce mucins or polarize, human cell line models that reproducibly
      create the combination of a polarized epithelial cell layer, functional tight
      junctions and an adherent mucus layer have been missing until now. We trialed a
      range of treatments to induce polarization, 3D-organization, tight junctions,
      mucin production, mucus secretion, and formation of an adherent mucus layer that
      can be carried out using standard equipment. These treatments were tested on cell
      lines of intestinal (Caco-2, LS513, HT29, T84, LS174T, HT29 MTX-P8 and HT29 MTX
      E12) and gastric (MKN7, MKN45, AGS, NCI-N87 and its hTERT Clone5 and Clone6)
      origins using Ussing chamber methodology and (immuno)histology. Semi-wet
      interface culture in combination with mechanical stimulation and DAPT caused HT29
      MTX-P8, HT29 MTX-E12 and LS513 cells to polarize, form functional tight
      junctions, a three-dimensional architecture resembling colonic crypts, and
      produce an adherent mucus layer. Caco-2 and T84 cells also polarized, formed
      functional tight junctions and produced a thin adherent mucus layer after this
      treatment, but with less consistency. In conclusion, culture methods affect cell
      lines differently, and testing a matrix of methods vs. cell lines may be
      important to develop better in vitro models. The methods developed herein create
      in vitro mucosal surfaces suitable for studies of host-pathogen interactions at
      the mucosal surface. 

PMID- 23869234
TI  - The impact of duration of treatment on reported time-to-onset in spontaneous
      reporting systems for pharmacovigilance.
AB  - Within pharmacovigilance, knowledge of time-to-onset (time from start of drug
      administration to onset of reaction) is important in causality assessment of
      drugs and suspected adverse drug reactions (ADRs) and may indicate
      pharmacological mechanisms involved. It has been suggested that time-to-onset
      from individual case reports can be used for detection of safety signals.
      However, some ADRs only occur during treatment, while those that do occur later
      are less likely to be reported. The aim of this study was to investigate the
      impact of treatment duration on the reported time-to-onset. Case reports from the
      WHO Global ICSR database, VigiBase, up until February 5(th) 2010 were the basis
      of this study. To examine the effect of duration of treatment on reported time-to
      onset, angioedema and hepatitis were selected to represent short and long latency
      ADRs, respectively. The reported time-to-onset for each of these ADRs was
      contrasted for a set of drugs expected to be used short- or long-term,
      respectively. The study included 2,980 unique reports for angioedema and 1,159
      for hepatitis. Median reported time-to-onset for angioedema in short-term
      treatments ranged 0-1 days (median 0.5), for angioedema in long-term treatments 0
      26 days (median 8), for hepatitis in short-term treatments 4-12 days (median 7.5)
      and for hepatitis in long term treatments 19-73 days (median 28). Short-term
      treatments presented significantly shorter reported time-to-onset than long-term
      treatments. Of note is that reported time-to-onset for angioedema for long-term
      treatments (median value of medians being 8 days) was very similar to that of
      hepatitis for short-term treatments (median value of medians equal 7.5 days). The
      expected duration of treatment needs to be considered in the interpretation of
      reported time-to-onset and should be accounted for in signal detection method
      development and case evaluation. 

PMID- 23869235
TI  - The severity of Osteogenesis imperfecta and type I collagen pattern in human skin
      as determined by nonlinear microscopy: proof of principle of a diagnostic method.
AB  - BACKGROUND: The confirmatory diagnosis of Osteogenesis Imperfecta (OI) requires
      invasive, commonly bone biopsy, time consuming and destructive methods. This
      paper proposes an alternative method using a combination of two-photon excitation
      fluorescence (TPEF) and second-harmonic generation (SHG) microscopies from easily
      obtained human skin biopsies. We show that this method can distinguish subtypes
      of human OI. METHODOLOGY/PRINCIPAL FINDINGS: Different aspects of collagen
      microstructure of skin fresh biopsies and standard H&E-stained sections of normal
      and OI patients (mild and severe forms) were distinguished by TPEF and SHG
      images. Moreover, important differences between subtypes of OI were identified
      using different methods of quantification such as collagen density, ratio between
      collagen and elastic tissue, and gray-level co-occurrence matrix (GLCM) image
      pattern analysis. Collagen density was lower in OI dermis, while the
      SHG/autofluorescence index of the dermis was significantly higher in OI as
      compared to that of the normal skin. We also showed that the energy value of GLCM
      texture analysis is useful to discriminate mild from severe OI and from normal
      skin. CONCLUSIONS/SIGNIFICANCE: This work demonstrated that nonlinear microscopy
      techniques in combination with image-analysis approaches represent a powerful
      tool to investigate the collagen organization in skin dermis in patients with OI
      and has the potential to distinguish the different types of OI. The procedure
      outlined in this paper requires a skin biopsy, which is almost painless as
      compared to the bone biopsy commonly used in conventional methods. The data
      presented here complement existing clinical diagnostic techniques and can be used
      as a diagnostic procedure to confirm the disease, evaluate its severity and
      treatment efficacy.

PMID- 23869236
TI  - Abnormal regional homogeneity in patients with essential tremor revealed by
      resting-state functional MRI.
AB  - Essential tremor (ET) is one of the most common movement disorders in human
      adults. It can be characterized as a progressive neurological disorder of which
      the most recognizable feature is a tremor of the arms or hands that is apparent
      during voluntary movements such as eating and writing. The pathology of ET
      remains unclear. Resting-state fMRI (RS-fMRI), as a non-invasive imaging
      technique, was employed to investigate abnormalities of functional connectivity
      in ET in the brain. Regional homogeneity (ReHo) was used as a metric of RS-fMRI
      to assess the local functional connectivity abnormality in ET with 20 ET patients
      and 20 age- and gender-matched healthy controls (HC). The ET group showed
      decreased ReHo in the anterior and posterior bilateral cerebellar lobes, the
      bilateral thalamus and the insular lobe, and increased ReHo in the bilateral
      prefrontal and parietal cortices, the left primary motor cortex and left
      supplementary motor area. The abnormal ReHo value of ET patients in the bilateral
      anterior cerebellar lobes and the right posterior cerebellar lobe were negatively
      correlated with the tremor severity score, while positively correlated with that
      in the left primary motor cortex. These findings suggest that the abnormality in
      cerebello-thalamo-cortical motor pathway is involved in tremor generation and
      propagation, which may be related to motor-related symptoms in ET patients.
      Meanwhile, the abnormality in the prefrontal and parietal regions may be
      associated with non-motor symptoms in ET. These findings suggest that the ReHo
      could be utilized for investigations of functional-pathological mechanism of ET. 

PMID- 23869237
TI  - Automated, high accuracy classification of Parkinsonian disorders: a pattern
      recognition approach.
AB  - Progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and
      idiopathic Parkinson's disease (IPD) can be clinically indistinguishable,
      especially in the early stages, despite distinct patterns of molecular pathology.
      Structural neuroimaging holds promise for providing objective biomarkers for
      discriminating these diseases at the single subject level but all studies to date
      have reported incomplete separation of disease groups. In this study, we employed
      multi-class pattern recognition to assess the value of anatomical patterns
      derived from a widely available structural neuroimaging sequence for automated
      classification of these disorders. To achieve this, 17 patients with PSP, 14 with
      IPD and 19 with MSA were scanned using structural MRI along with 19 healthy
      controls (HCs). An advanced probabilistic pattern recognition approach was
      employed to evaluate the diagnostic value of several pre-defined anatomical
      patterns for discriminating the disorders, including: (i) a subcortical motor
      network; (ii) each of its component regions and (iii) the whole brain. All
      disease groups could be discriminated simultaneously with high accuracy using the
      subcortical motor network. The region providing the most accurate predictions
      overall was the midbrain/brainstem, which discriminated all disease groups from
      one another and from HCs. The subcortical network also produced more accurate
      predictions than the whole brain and all of its constituent regions. PSP was
      accurately predicted from the midbrain/brainstem, cerebellum and all basal
      ganglia compartments; MSA from the midbrain/brainstem and cerebellum and IPD from
      the midbrain/brainstem only. This study demonstrates that automated analysis of
      structural MRI can accurately predict diagnosis in individual patients with
      Parkinsonian disorders, and identifies distinct patterns of regional atrophy
      particularly useful for this process. 

PMID- 23869239
TI  - A meta-analysis on the relationship between exposure to ELF-EMFs and the risk of
      female breast cancer.
AB  - OBJECTIVE: To comprehensively analyze the relationship between exposure to
      extremely low frequency electromagnetic fields (ELF-EMFs) and the development of
      female breast cancer. METHODS: Reports of case-control studies published from
      1990 to 2010 were analyzed. The quality effect model was chosen to calculate
      total odds ratio (OR) depending on the data in studies and quality scores.
      Subgroup analyses were also performed by the situation of menopause, estrogenic
      receptor and exposure assessment respectively. RESULTS: For all 23 studies the OR
      was 1.07, 95% CI=1.02-1.13, for estrogen receptor positive subgroup,OR=1.11, 95%
      CI=1.03-1.20; for premenopausal subgroup, OR=1.11, 95% CI=1.00-1.23. The results
      of other subgroups showed no significant association between ELF-EMF and female
      breast cancer. CONCLUSION: ELF-EMFs might be related to an increased risk for
      female breast cancer, especially for premenopausal and ER+ females. However, it's
      necessary to undertake better epidemiologic researches to verify the association
      between ELF-EMF and female breast cancer due to the limits of current study,
      especially the one on exposure assessment.

PMID- 23869238
TI  - Berberine Targets AP-2/hTERT, NF-kappaB/COX-2, HIF-1alpha/VEGF and Cytochrome
      c/Caspase Signaling to Suppress Human Cancer Cell Growth.
AB  - Berberine (BBR), an isoquinoline derivative alkaloid isolated from Chinese herbs,
      has a long history of uses for the treatment of multiple diseases, including
      cancers. However, the precise mechanisms of actions of BBR in human lung cancer
      cells remain unclear. In this study, we investigated the molecular mechanisms by
      which BBR inhibits cell growth in human non-small-cell lung cancer (NSCLC) cells.
      Treatment with BBR promoted cell morphology change, inhibited cell migration,
      proliferation and colony formation, and induced cell apoptosis. Further molecular
      mechanism study showed that BBR simultaneously targeted multiple cell signaling
      pathways to inhibit NSCLC cell growth. Treatment with BBR inhibited AP-2alpha and
      AP-2beta expression and abrogated their binding on hTERT promoters, thereby
      inhibiting hTERT expression. Knockdown of AP-2alpha and AP-2beta by siRNA
      considerably augmented the BBR-mediated inhibition of cell growth. BBR also
      suppressed the nuclear translocation of p50/p65 NF-kappaB proteins and their
      binding to COX-2 promoter, causing inhibition of COX-2. BBR also downregulated
      HIF-1alpha and VEGF expression and inhibited Akt and ERK phosphorylation.
      Knockdown of HIF-1alpha by siRNA considerably augmented the BBR-mediated
      inhibition of cell growth. Moreover, BBR treatment triggered cytochrome-c release
      from mitochondrial inter-membrane space into cytosol, promoted cleavage of
      caspase and PARP, and affected expression of BAX and Bcl-2, thereby activating
      apoptotic pathway. Taken together, these results demonstrated that BBR inhibited
      NSCLC cell growth by simultaneously targeting AP-2/hTERT, NF-kappaB/COX-2, HIF
      1alpha/VEGF, PI3K/AKT, Raf/MEK/ERK and cytochrome-c/caspase signaling pathways.
      Our findings provide new insights into understanding the anticancer mechanisms of
      BBR in human lung cancer therapy. 

PMID- 23869240
TI  - Triglyceride/HDL ratio as a screening tool for predicting success at reducing
      anti-diabetic medications following weight loss.
AB  - BACKGROUND AND OBJECTIVES: Intentional weight loss, by reducing insulin
      resistance, results in both better glycemic control and decreased need for anti
      diabetic medications. However, not everyone who is successful with weight loss is
      able to reduce anti-diabetic medication use. In this retrospective cohort study,
      we assessed the predictive accuracy of baseline triglyceride (TGL)/HDL ratio, a
      marker of insulin resistance, to screen patients for success in reducing anti
      diabetic medication use with weight loss. METHODS: Case records of 121 overweight
      and obese attendees at two outpatient weight management centers were analyzed.
      The weight loss intervention consisted of a calorie-restricted diet
      (~1000Kcal/day deficit), a behavior modification plan, and a plan for increasing
      physical activity. RESULTS: Mean period of follow-up was 12.5 +/- 3.5 months. By
      study exit, mean weight loss and mean HbA1c% reduction were 15.4 +/- 5.5 kgs and
      0.5 +/- 0.2% respectively. 81 (67%) in the study cohort achieved at least 1 dose
      reduction of any anti-diabetic medication. Tests for predictive accuracy of
      baseline TGL/HDL ratio <= 3 to determine success with dose reductions of anti
      diabetic medications showed a sensitivity, specificity, positive predictive
      value, negative predictive value, area under the curve, likelihood ratio (LR) +
      and LR-of 81, 83, 90, 70, 78, 4.8 and 0.2, respectively. Reproducibility of
      TGL/HDL ratio was acceptable. CONCLUSION: TGL/HDL ratio shows promise as an
      effective screening tool to determine success with dose reductions of anti
      diabetic medications. The results of our study may inform the conduct of a
      systematic review using data from prior weight loss trials.

PMID- 23869241
TI  - Advanced mathematical study and the development of conditional reasoning skills.
AB  - Since the time of Plato, philosophers and educational policy-makers have assumed
      that the study of mathematics improves one's general 'thinking skills'. Today,
      this argument, known as the 'Theory of Formal Discipline' is used in policy
      debates to prioritize mathematics in school curricula. But there is no strong
      research evidence which justifies it. We tested the Theory of Formal Discipline
      by tracking the development of conditional reasoning behavior in students
      studying post-compulsory mathematics compared to post-compulsory English
      literature. In line with the Theory of Formal Discipline, the mathematics
      students did develop their conditional reasoning to a greater extent than the
      literature students, despite them having received no explicit tuition in
      conditional logic. However, this development appeared to be towards the so-called
      defective conditional understanding, rather than the logically normative material
      conditional understanding. We conclude by arguing that Plato may have been
      correct to claim that studying advanced mathematics is associated with the
      development of logical reasoning skills, but that the nature of this development
      may be more complex than previously thought. 

PMID- 23869242
TI  - Streptococcus pyogenes c-di-AMP phosphodiesterase, GdpP, influences SpeB
      processing and virulence.
AB  - Small cyclic nucleotide derivatives are employed as second messengers by both
      prokaryotes and eukaryotes to regulate diverse cellular processes responding to
      various signals. In bacteria, c-di-AMP has been discovered most recently, and
      some Gram-positive pathogens including S. pyogenes use this cyclic nucleotide
      derivative as a second messenger instead of c-di-GMP, a well-studied important
      bacterial second messenger. GdpP, c-di-AMP phosphodiesterase, is responsible for
      degrading c-di-AMP inside cells, and the cellular role of GdpP in S. pyogenes has
      not been examined yet. To test the cellular role of GdpP, we created a strain
      with a nonpolar inframe deletion of the gdpP gene, and examined the properties of
      the strain including virulence. From this study, we demonstrated that GdpP
      influences the biogenesis of SpeB, the major secreted cysteine protease, at a
      post-translational level, susceptibility to the beta lactam antibiotic
      ampicillin, and is necessary for full virulence in a murine subcutaneous
      infection model. 

PMID- 23869243
TI  - Effects of the plant growth-promoting bacterium Burkholderia phytofirmans PsJN
      throughout the life cycle of Arabidopsis thaliana.
AB  - Plant growth-promoting rhizobacteria (PGPR) induce positive effects in plants,
      such as increased growth or reduced stress susceptibility. The mechanisms behind
      PGPR/plant interaction are poorly understood, as most studies have described
      short-term responses on plants and only a few studies have analyzed plant
      molecular responses under PGPR colonization. Here, we studied the effects of the
      PGPR bacterial model Burkholderiaphytofirmans PsJN on the whole life cycle of
      Arabidopsis thaliana plants. We reported that at different plant developmental
      points, strain PsJN can be found in the rhizosphere and also colonizing their
      internal tissues. In early ontogeny, strain PsJN increased several growth
      parameters and accelerated growth rate of the plants. Also, an Arabidopsis
      transcriptome analysis revealed that 408 genes showed differential expression in
      PsJN-inoculated plants; some of these genes are involved in stress response and
      hormone pathways. Specifically, genes implicated in auxin and gibberellin
      pathways were induced. Quantitative transcriptional analyses of selected genes in
      different developmental stages revealed that the beginning of these changes could
      be evidenced early in development, especially among the down-regulated genes. The
      inoculation with heat-killed bacteria provoked a more severe transcriptional
      response in plants, but was not able to induce plant growth-promotion. Later in
      ontogeny, the growth rates of inoculated plants decreased with respect to the non
      inoculated group and, interestingly, the inoculation accelerated the flowering
      time and the appearance of senescence signs in plants; these modifications
      correlate with the early up-regulation of flowering control genes. Then, we show
      that a single inoculation with a PGPR could affect the whole life cycle of a
      plant, accelerating its growth rate and shortening its vegetative period, both
      effects relevant for most crops. Thus, these findings provide novel and
      interesting aspects of these relevant biological interactions. 

PMID- 23869244
TI  - Mitochondrial capture misleads about ecological speciation in the Daphnia pulex
      complex.
AB  - The North American ecological species Daphniapulicaria and Daphniapulex are
      thought to have diverged from a common ancestor by adaptation to sympatric but
      ecologically distinct lake and pond habitats respectively. Based on mtDNA
      relationships, European D. pulicaria is considered a different species only
      distantly related to its North American counterpart, but both species share a
      lactate dehydrogenase (Ldh) allele F supposedly involved in lake adaptation in
      North America, and the same allele is also carried by the related Holarctic
      Daphniatenebrosa. The correct inference of the species' ancestral relationships
      is therefore critical for understanding the origin of their adaptive divergence.
      Our species tree inferred from unlinked nuclear loci for D. pulicaria and D.
      pulex resolved the European and North American D. pulicaria as sister clades, and
      we argue that the discordant mtDNA gene tree is best explained by capture of D.
      pulex mtDNA by D. pulicaria in North America. The Ldh gene tree shows that F
      class alleles in D. pulicaria and D. tenebrosa are due to common descent (as
      opposed to introgression), with D. tenebrosa alleles paraphyletic with respect to
      D. pulicaria alleles. That D. tenebrosa still segregates the ancestral and
      derived amino acids at the two sites distinguishing the pond and lake alleles
      suggests that D. pulicaria inherited the derived states from the D. tenebrosa
      ancestry. Our results suggest that some adaptations restricting the gene flow
      between D. pulicaria and D. pulex might have evolved in response to selection in
      ancestral environments rather than in the species' current sympatric habitats.
      The Arctic (D. tenebrosa) populations are likely to provide important clues about
      these issues. 

PMID- 23869245
TI  - Activation of Wnt/beta-catenin signaling increases apoptosis in melanoma cells
      treated with trail.
AB  - While the TRAIL pathway represents a promising therapeutic target in melanoma,
      resistance to TRAIL-mediated apoptosis remains a barrier to its successful
      adoption. Since the Wnt/beta-catenin pathway has been implicated in facilitating
      melanoma cell apoptosis, we investigated the effect of Wnt/beta-catenin signaling
      on regulating the responses of melanoma cells to TRAIL. Co-treatment of melanoma
      cell lines with WNT3A-conditioned media and recombinant TRAIL significantly
      enhanced apoptosis compared to treatment with TRAIL alone. This apoptosis
      correlates with increased abundance of the pro-apoptotic proteins BCL2L11 and
      BBC3, and with decreased abundance of the anti-apoptotic regulator Mcl1. We then
      confirmed the involvement of the Wnt/beta-catenin signaling pathway by
      demonstrating that siRNA-mediated knockdown of an intracellular beta-catenin
      antagonist, AXIN1, or treating cells with an inhibitor of GSK-3 also enhanced
      melanoma cell sensitivity to TRAIL. These studies describe a novel regulation of
      TRAIL sensitivity in melanoma by Wnt/beta-catenin signaling, and suggest that
      strategies to enhance Wnt/beta-catenin signaling in combination with TRAIL
      agonists warrant further investigation. 

PMID- 23869247
TI  - Eosinophilic presentation of acute lymphoblastic leukemia.
AB  - PATIENT: Male, 5 Primary Diagnosis: Rule-out appendicitis Co-existing Diseases:
      Acute lymphoblastic leukemia (ALL) Medication: Chemiotherapy Clinical Procedure:
      Chest CT * flow cytometry Specialty: Pediatrics' oncology * infection diseases.
      OBJECTIVE: Rare disease. BACKGROUND: Leukemias are among the most common
      childhood malignancies. Acute lymphoblastic leukemia (ALL) accounts for 77% of
      all leukemias. In rare cases, ALL patients may present with eosinophilia. CASE
      REPORT: Here, a 5-year old boy was admitted to our hospital with a possible
      diagnosis of appendicitis. This patient's complete blood cell count demonstrated
      leukocytosis with severe eosinophilia. Following a 1-month clinical
      investigation, 2 bone marrow aspirations, and flow cytometry analysis, a
      diagnosis of acute lymphoblastic leukemia was proposed. Finally, the patient was
      transferred to the oncology ward to receive standard therapeutic protocol, which
      resulted in disease remission. After chemotherapy for 2 years, patient is
      successfully treated. CONCLUSIONS: ALL is diagnosed by eosinophilia in rare
      cases. These patients need immediate diagnosis and intensive therapy due to
      worsened prognosis of ALL presenting as hypereosinophilia.

PMID- 23869246
TI  - An extensive comparison of the effect of anthelmintic classes on diverse
      nematodes.
AB  - Soil-transmitted helminths are parasitic nematodes that inhabit the human
      intestine. These parasites, which include two hookworm species,
      Ancylostomaduodenale and Necator americanus, the whipworm Trichuristrichiura, and
      the large roundworm Ascarislumbricoides, infect upwards of two billion people and
      are a major cause of disease burden in children and pregnant women. The challenge
      with treating these diseases is that poverty, safety, and inefficient public
      health policy have marginalized drug development and distribution to control
      infection in humans. Anthelmintics (anti-worm drugs) have historically been
      developed and tested for treatment of non-human parasitic nematodes that infect
      livestock and companion animals. Here we systematically compare the in vitro
      efficacy of all major anthelmintic classes currently used in human therapy
      (benzimidazoles, nicotinic acetylcholine receptor agonists, macrocyclic lactones,
      nitazoxanide) against species closely related to human parasitic nematodes
      Ancylostoma ceylanicum, Trichurismuris, and Ascarissuum--- as well as a rodent
      parasitic nematode used in veterinary drug discovery, Heligmosomoidesbakeri, and
      the free-living nematode Caenorhabditis elegans. Extensive in vitro data is
      complemented with single-dose in vivo data in three rodent models of parasitic
      diseases. We find that the effects of the drugs in vitro and in vivo can vary
      greatly among these nematode species, e.g., the efficacy of albendazole is strong
      on A. ceylanicum but weak on H. bakeri. Nonetheless, certain commonalities of the
      in vitro effects of the drugs can be seen, e.g., nitazoxanide consistently shows
      an all-or-nothing response. Our in vitro data suggest that further optimization
      of the clinical efficacy of some of these anthelmintics could be achieved by
      altering the treatment routine and/or dosing. Most importantly, our in vitro and
      in vivo data indicate that the hookworm A. ceylanicum is a particularly sensitive
      and useful model for anthelmintic studies and should be incorporated early on in
      drug screens for broad-spectrum human soil-transmitted helminth therapies. 

PMID- 23869248
TI  - Large benign submucosal lipoma presented with descending colonic intussusception
      in an adult.
AB  - PATIENT: Female, 34 FINAL DIAGNOSIS: Lipoma of the large intestine Symptoms:
      Abdominal pain * bloating * blood in stool * constipation * lose of appetite *
      nausea MEDICATION: - Clinical Procedure: - Specialty: Surgery. OBJECTIVE: Rare
      disease. BACKGROUND: Lipoma of the large intestine is rare, account for only 5%
      of all gastrointestinal tumors. Lipomas are usually asymptomatic but rarely may
      cause bleeding, obstruction and intussusception. We present a case of a giant
      colonic lipoma causing descending-colonic intussusception. CASE REPORT: 34 yo F
      presented with the intermittent left lower quadrant abdominal pain for 3 weeks.
      The pain initially was associated with bloating and constipation and for the last
      several days frank blood in stool, nausea and decreased appetite. CT scan of the
      abdomen revealed descending colonic obstruction by a 5.3 cm colonic lipomatous
      mass with resultant intussusception. PATIENT initially underwent colonoscopy that
      revealed polypoid lesion at 3-40 similar to lipoma with intussusception that was
      reduced. PATIENT subsequently underwent laparoscopic segmental left colectomy for
      the descending colonic intussusception due to large colonic lipomatous mass.
      Pathology confirmed the histology of lipoma. CONCLUSIONS: Adult bowel
      intussusception is a rare but challenging condition to diagnose in a timely
      manner. Preoperative diagnosis is usually missed or delayed because of
      nonspecific and often subacute symptoms. Lipoma is a rare cause of the
      intussusception. A high index of suspicion and appropriate investigations
      (abdominal ultrasound, CT scan and colonoscopy) can result in prompt diagnosis.
      Lipoma of the large intestine is very rare. Submucosal lipomas are usually
      asymptomatic but may cause bleeding, obstruction, intussusception, or abdominal
      pain. Accurate preoperative diagnosis is difficult and lipoma is often mistaken
      for adenomatous polyp or carcinoma. Treatment usually requires formal resection
      of the involved bowel segment due to high suspicion for malignancy and subsequent
      complications due to obstruction.

PMID- 23869249
TI  - Rhabdomyosarcoma of the breast - a rare malignancy.
AB  - PATIENT: Female, 60 FINAL DIAGNOSIS: Rhabdomyosarcoma of the breast Symptoms:
      Lump in axilla Medication: - Clinical Procedure: Mastectomy Specialty: Oncology.
      OBJECTIVE: Rare disease. BACKGROUND: Primary nonepithelial malignancies of the
      breast include primary breast sarcomas, therapy-related breast sarcomas, the
      phyllodes tumors, and primary breast lymphomas. They account for less than 5% of
      all breast neoplasms. CASE REPORT: We report the case of a 60-year-old
      postmenopausal female diagnosed with rhabdomyosarcoma with infiltrating duct
      carcinoma. She was treated with modified radical mastectomy with axillary
      clearance and postoperative chemotherapy. CONCLUSIONS: Primary rhabdomyosarcoma
      of the breast in adults is extremely rare. Rhabdomyosarcomas in adults account
      for less than 3% of all adult primary soft-tissue sarcomas. Primary breast
      sarcomas usually present as large painless breast lumps with no associated skin
      and nipple changes or axillary lymphadenopathy; they are more aggressive and have
      more rapid growth than epithelial malignancies or benign breast lesions. The
      tumor can grow to large size, around 5.8 cm. Affected patients are typically
      women in their 50 s (ranging from 17 to 89 years), but it is also seen in men.
      The treatment of primary breast sarcomas requires a multidisciplinary approach.
      Surgery remains the mainstay of therapy. Chemotherapy has no clearly defined role
      in primary breast or soft-tissue sarcomas. The prognosis of primary breast
      sarcomas depends on the histologic grade and size of the tumor. They spread
      locally and hematogenously, but they are not usually associated with axillary
      lymphadenopathy.

PMID- 23869250
TI  - The Role of Social Support in Exposure Therapy for Operation Iraqi
      Freedom/Operation Enduring Freedom Veterans: A Preliminary Investigation.
AB  - The lack of social support has consistently been identified as a relevant factor
      in the development, maintenance, and treatment of posttraumatic stress disorder
      (PTSD). Prospective studies with combat veterans have supported the erosion model
      of social support in the development of PTSD. This model posits that increased
      PTSD symptoms lead to diminished social support over time. Additional
      epidemiological work that has investigated mental health and functional
      impairment in recently returning Operation Iraqi Freedom and Operation Enduring
      Freedom (OIF/OEF) veterans has suggested that interpersonal problems coincide
      with the onset of PTSD. Despite research that suggests OIF/OEF veterans
      experience high rates of PTSD and associated interpersonal problems, no studies
      have examined social support in relation to treatment response in this group. The
      current study examined the role of four theorized functional aspects of social
      support- emotional/informational support, positive social interactions,
      affectionate support, and tangible support- on pretreatment PTSD symptom severity
      and treatment response in a sample of OIF/OEF veterans receiving exposure-based
      psychotherapy. Findings showed that positive social interactions were negatively
      correlated with pretreatment symptom severity, and emotional/informational
      support was positively related to increased treatment response. Together, these
      findings suggest that specific types of social support may have an important
      influence on the course of exposure treatment.

PMID- 23869251
TI  - Distal amputations for the diabetic foot.
AB  - Minor amputations in diabetic patients with foot complications have been well
      studied in the literature but controversy still remains as to what constitutes
      successful or non-successful limb salvage. In addition, there is a lack of
      consensus on the definition of a minor or distal amputation and a major or
      proximal amputation for the diabetic population. In this article, the authors
      review the existing literature to evaluate the efficacy of minor amputations in
      this selected group of patients in terms of diabetic limb salvage and also
      propose several definitions regarding diabetic foot amputations. 

PMID- 23869252
TI  - Trauma histories among justice-involved youth: findings from the National Child
      Traumatic Stress Network.
AB  - BACKGROUND: Up to 90% of justice-involved youth report exposure to some type of
      traumatic event. On average, 70% of youth meet criteria for a mental health
      disorder with approximately 30% of youth meeting criteria for post-traumatic
      stress disorder (PTSD). Justice-involved youth are also at risk for substance use
      and academic problems, and child welfare involvement. Yet, less is known about
      the details of their trauma histories, and associations among trauma details,
      mental health problems, and associated risk factors. OBJECTIVE: This study
      describes detailed trauma histories, mental health problems, and associated risk
      factors (i.e., academic problems, substance/alcohol use, and concurrent child
      welfare involvement) among adolescents with recent involvement in the juvenile
      justice system. METHOD: The National Child Traumatic Stress Network Core Data Set
      (NCTSN-CDS) is used to address these aims, among which 658 adolescents report
      recent involvement in the juvenile justice system as indexed by being detained or
      under community supervision by the juvenile court. RESULTS: Age of onset of
      trauma exposure was within the first 5 years of life for 62% of youth and
      approximately one-third of youth report exposure to multiple or co-occurring
      trauma types each year into adolescence. Mental health problems are prevalent
      with 23.6% of youth meeting criteria for PTSD, 66.1% in the clinical range for
      externalizing problems, and 45.5% in the clinical range for internalizing
      problems. Early age of onset of trauma exposure was differentially associated
      with mental health problems and related risk factors among males and females.
      CONCLUSIONS: The results indicate that justice-involved youth report high rates
      of trauma exposure and that this trauma typically begins early in life, is often
      in multiple contexts, and persists over time. Findings provide support for
      establishing trauma-informed juvenile justice systems that can respond to the
      needs of traumatized youth.

PMID- 23869253
TI  - The Dopamine Receptor D4 Gene 7-Repeat Allele Interacts with Parenting Quality to
      Predict Effortful Control in Four-Year-Old Children.
AB  - The dopamine receptor D4 gene (DRD4) 7-repeat allele has been found to interact
      with environmental factors such as parenting in children and peer attitudes in
      adults to influence aspects of behavior such as risk taking. We previously found
      that in toddlers, lower-quality parenting in combination with the 7-repeat allele
      of the DRD4 gene was associated with greater parent-reported Sensation Seeking
      (SS), but was unrelated to Effortful Control (EC). We now report findings from a
      followup assessment with the same sample of children showing that parenting
      quality interacts with the presence of the 7-repeat allele to predict EC in 3-to
      4-year-old children. The change in these patterns of results may reflect the
      increased role of the executive attention network in older children and adults.
      However, due to the small sample size (N = 52) and the novelty of the results,
      these findings should be treated with caution and considered preliminary until
      they are replicated in an independent sample.

PMID- 23869254
TI  - The Tousled-Like Kinases as Guardians of Genome Integrity.
AB  - The Tousled-like kinases (TLKs) function in processes of chromatin assembly,
      including replication, transcription, repair, and chromosome segregation. TLKs
      interact specifically (and phosphorylate) with the chromatin assembly factor
      Asf1, a histone H3-H4 chaperone, histone H3 itself at Ser10, and also Rad9, a key
      protein involved in DNA repair and cell cycle signaling following DNA damage.
      These interactions are believed to be responsible for the action of TLKs in
      double-stranded break repair and radioprotection and also in the propagation of
      the DNA damage response. Hence, I propose that TLKs play key roles in maintenance
      of genome integrity in many organisms of both kingdoms. In this paper, I
      highlight key issues of the known roles of these proteins, particularly in the
      context of DNA repair (IR and UV), their possible relevance to genome integrity
      and cancer development, and as possible targets for intervention in cancer
      management.

PMID- 23869255
TI  - Biocompatability of carbon nanotubes with stem cells to treat CNS injuries.
AB  - Cases reporting traumatic injuries to the brain and spinal cord are extended
      range of disorders that affect a large percentage of the world's population. But,
      there are only few effective treatments available for central nervous system
      (CNS) injuries because the CNS is refractory to axonal regeneration and
      relatively inaccessible to many pharmacological treatments. The use of stem cell
      therapy in regenerative medicine has been extensively examined to replace lost
      cells during CNS injuries. But, given the complexity of CNS injuries oxidative
      stress, toxic byproducts, which prevails in the microenvironment during the
      diseased condition, may limit the survival of the transplanted stem cells
      affecting tissue regeneration and even longevity. Carbon nanotubes (CNT) are a
      new class of nanomaterials, which have been shown to be promising in different
      areas of nanomedicine for the prevention, diagnosis and therapy of certain
      diseases, including CNS diseases. In particular, the use of CNTs as
      substrates/scaffolds for supporting the stem cell differentiation has been an
      area of active research. Single-walled and multi-walled CNT's have been
      increasingly used as scaffolds for neuronal growth and more recently for neural
      stem cell growth and differentiation. This review summarizes recent research on
      the application of CNT-based materials to direct the differentiation of
      progenitor and stem cells toward specific neurons and to enhance axon
      regeneration and synaptogenesis for the effective treatment of CNS injuries.
      Nonetheless, accumulating data support the use of CNTs as a biocompatible and
      permissive substrate/scaffold for neural cells and such application holds great
      potential in neurological research. 

PMID- 23869256
TI  - Surgical anatomy of the upper eyelid relating to upper blepharoplasty or
      blepharoptosis surgery.
AB  - Eyelid anatomy, including thickness measurements, was examined in numerous age
      groups. The thickest part of the upper eyelid is just below the eyebrow (1.127+/
      238 um), and the thinnest near the ciliary margin (320+/-49 um). The thickness of
      skin at 7 mm above the eyelashes was 860+/-305 um. The results revealed no
      significant differences among the age groups. Fast fibers (87.8+/-3.7%) occupied
      a significantly larger portion of the orbicularis oculi muscle (OOM) than nonfast
      fibers (12.2+/-3.7%). The frontalis muscle passed through and was inserted into
      the bundles of the OOM on the superior border of the eyebrow at the middle and
      medial portions of the upper eyelid. Laterally, the frontalis muscle inserted
      about 0.5 cm below the superior border of the eyebrow. Fast fibers occupied a
      significantly larger portion of the OOM than did non-fast fibers. The oculomotor
      nerve ends that extend forward to the distal third of the levator muscle are
      exposed and vulnerable to local anesthetics and may be numbed during
      blepharoplasty. The orbital septum consists of 2 layers. The outer layer of loose
      connective tissue descends to interdigitate with the levator aponeurosis and
      disperses inferiorly. The inner layer follows the outer layer, then reflects and
      continues posteriorly with the levator sheath. Widths of the tarsal plate at its
      lower border, mid-height, and upper border were 21.8+/-1.8, 16.2+/-1.6, and 8.3+/
      1.0 mm, respectively. The widths of the levator aponeurosis were 32.0+/-2.2,
      29.2+/-3.5, and 27.2+/-3.9 mm, respectively. Below the levator, the "conjoint
      fascial sheath" (CFS) is attached to the conjunctival fornix. The CFS was 12.2+/
      2.0 mm anteroposterior length and 1.1+/-0.1 mm thick. The shape was equilateral
      trapezoid with a longer base anteriorly. The superior palpebral muscle was
      trapezoidal. The lengths of its sides were 15.58+/-1.82 and 22.30+/-5.25 mm, and
      its height was 13.70+/-2.74 mm. The width of the levator aponeurosis was
      approximately 4 mm wider than the superior palpebral muscle. 

PMID- 23869257
TI  - Heterogeneity of glandular cells in the human salivary glands: an
      immunohistochemical study using elderly adult and fetal specimens.
AB  - Using immunohistochemical staining for alpha-smooth muscle actin (alpha-SMA),
      glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14
      (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of
      major and minor salivary glands obtained from 14 donated cadavers (78-92 years
      old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63
      expression was investigated only in the adult specimens. SMA was detected in all
      adult glands as well as in fetal sublingual and pharyngeal glands. GFAP
      expression was seen in a limited number of cells in adult glands, but was highly
      expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were
      present in adult minor glands as well as in fetal sublingual and pharyngeal
      glands. Expression of p63 was evident in the ducts of adult glands. CK14
      immunoreactivity was observed in a limited number of glandular cells in adults,
      in contrast to consistent expression of CK19. In both adults and fetuses, a
      mosaic expression pattern was usually evident for each of the examined proteins.
      A difference in immunoreactivity for the nerve markers GFAP and S100 was observed
      between the major and minor glands. Thus, in the present histologic study, we
      distinguished between the specific gland types on the basis of their
      immunohistochemical staining. A mosaic expression pattern suggested that the
      immunoreactivity against nerve protein markers in myoepithelial cells could not
      be due to the persistence of neural crest remnants or the physiological status of
      the gland, such as age-related degeneration. 

PMID- 23869258
TI  - Expression of surface markers and myogenic potential of rat bone marrow- and
      adipose-derived stem cells: a comparative study.
AB  - In recent years, examination and comparison of the biological characteristics of
      bone marrow- and adipose-derived mesenchymal stem cells (MSCs) from various
      perspectives have come into the focus of stem cell research, as these cells
      should be well characterized in order to utilize them in future cellular
      therapies. Therefore, in the present study, surface protein markers and the
      skeletal myogenic differentiation potential of rat bone marrow- and adipose
      derived MSCs were examined. The expression of CD44, CD45, CD73, and CD90 on bone
      marrow- and adipose-derived MSCs was characterized using flow cytometry.
      Subsequently, the stem cells were differentiated into myogenic lineages, and the
      expression of the skeletal myogenic markers MyoD1, Myog, and Myh2 was studied in
      cells using real time polymerase chain reaction and immunofluorescence. Our
      results reveal that the pattern of CD marker expression differs between these 2
      types of MSCs to some extent, whereas no significant difference was observed with
      respect to their myogenic differentiation potential. Therefore, we concluded that
      despite the differences observed in the biological features of these 2 types of
      MSCs, their myogenic potential appears to be similar, and that adipose-derived
      stem cells may be useful in skeletal muscle tissue engineering, due to their easy
      isolation and capacity for rapid expansion in a short time span. 

PMID- 23869259
TI  - Effect of Ocimum basilicum extract on cadmium-induced testicular
      histomorphometric and immunohistochemical alterations in albino rats.
AB  - The present study examined the efficacy of Ocimum basilicum (basil) extract, a
      natural herb, with antioxidant properties, against testicular toxicity induced by
      cadmium (Cd), which is one of the most important toxic heavy metals. The
      intoxicated rats showed significant alterations in the testicular tissue
      including decreased seminiferous epithelium height and changes in the arrangement
      of spermatogenic layers. Hypospermatogensis with cytoplasmic vacuolization and
      pyknotic nuclei were observed. Intertubular hemorrahage and absence of
      spermatozoa were noted. Decreased cell proliferation was reflected by a decrease
      in Ki-67 expression, whereas the increase in apoptotic rate was associated with a
      decrease in the Bcl/Bax ratio. Concomitant treatment with aqueous basil extract
      led to an improvement in histological, morphometrical and immunohistochemical
      changes induced by Cd. The beneficial effects of basil extract could be
      attributed to its antioxidant properties. 

PMID- 23869260
TI  - Characterization of nestin expression in astrocytes in the rat hippocampal CA1
      region following transient forebrain ischemia.
AB  - Recent studies have suggested that nestin facilitates cellular structural
      remodeling in vasculature-associated cells in response to ischemic injury. The
      current study was designed to investigate the potential role of post-ischemic
      nestin expression in parenchymal astrocytes. With this aim, we characterized
      ischemia-induced nestin expression in the CA1 hippocampal region, an area that
      undergoes a delayed neuronal death, followed by a lack of neuronal generation
      after transient forebrain ischemia. Virtually all of the nestin-positive cells in
      the ischemic CA1 hippocampus were reactive astrocytes. However, induction of
      nestin expression did not correlate simply with astrogliosis, but rather showed
      characteristic time- and strata-dependent expression patterns. Nestin induction
      in astrocytes of the pyramidal cell layer was rapid and transient, while a long
      lasting induction of nestin was observed in astrocytes located in the CA1
      dendritic subfields, such as the stratum oriens and radiatum, until at least day
      28 after ischemia. There was no detectable expression in the stratum lacunosum
      moleculare despite the evident astroglial reaction. Almost all of the nestin
      positive cells also expressed a transcription factor for neural/glial
      progenitors, i.e., Sox-2 or Sox-9, and some cells were also positive for Ki-67.
      However, all of the nestin-positive astrocytes expressed the calcium-binding
      protein S100beta, which is known to be expressed in a distinct, post-mitotic
      astrocyte population. Thus, our data indicate that in the ischemic CA1
      hippocampus, nestin expression was induced in astroglia that were becoming
      reactive, but not in a progenitor/stem cell population, suggesting that nestin
      may allow for the structural remodeling of these cells in response to ischemic
      injury. 

PMID- 23869261
TI  - Fetal anatomy of the upper pharyngeal muscles with special reference to the nerve
      supply: is it an enteric plexus or simply an intramuscular nerve?
AB  - We examined pharyngeal nerve courses in paraffin-embedded sagittal sections from
      10 human fetuses, at 25-35 weeks of gestation, by using S100 protein
      immunohistochemical analysis. After diverging from the glossopharyngeal and vagus
      nerves at the level of the hyoid bone, the pharyngeal nerves entered the
      constrictor pharyngis medius muscle, then turned upward and ran superiorly and
      medially through the constrictor pharyngis superior muscle, to reach either the
      levator veli palatini muscle or the palatopharyngeus muscle. None of the nerves
      showed a tendency to run along the posterior surface of the pharyngeal muscles.
      Therefore, the pharyngeal nerve plexus in adults may become established by
      exposure of the fetal intramuscular nerves to the posterior aspect of the
      pharyngeal wall because of muscle degeneration and the subsequent rearrangement
      of the topographical relationship between the muscles that occurs after birth. 

PMID- 23869262
TI  - Influence of developing ligaments on the muscles in contact with them: a study of
      the annular ligament of the radius and the sacrospinous ligament in mid-term
      human fetuses.
AB  - The supinator muscle originates from the annular ligament of the radius, and the
      muscle fibers and ligament take a similar winding course. Likewise, the coccygeus
      muscle and the sacrospinous ligament are attached together, and show a similar
      fiber orientation. During dissection of adult cadavers for our educational
      curriculum, we had the impression that these ligaments grow in combination with
      degeneration of parts of the muscles. In histological sections of 25 human
      fetuses at 10-32 weeks of gestation, we found that the proximal parts of the
      supinator muscle were embedded in collagenous tissue when the developing annular
      ligament of the radius joined the thick intermuscular connecting band extending
      between the extensor carpi radialis and anconeus muscles at 18-22 weeks of
      gestation, and the anterior parts of the coccygeus muscle were surrounded by
      collagenous tissue when the intramuscular tendon became the sacrospinous ligament
      at 28-32 weeks. Parts of these two muscles each seemed to provide a mold for the
      ligament, and finally became involved with it. This may be the first report to
      indicate that a growing ligament has potential to injure parts of the "mother
      muscle," and that this process may be involved in the initial development of the
      ligament. 

PMID- 23869263
TI  - Students' perception of anatomy education at a Korean medical college with
      respect to time and contents.
AB  - Among medical education institutions worldwide, the time allotted for anatomy
      instruction has decreased without any reasonable time optimization suggestions.
      In addition, the utility of cadaver dissection has long been debated. Herein, we
      surveyed students' perceptions of anatomy education with respect to time and
      hands-on cadaver dissection, at Seoul National University College of Medicine.
      With the help of a questionnaire, we surveyed third- and fourth-year students at
      our institute who had completed the anatomy module as freshmen as well as their
      clinical clerkship. At our institute, students complete 50 hours of anatomy
      lectures and 120 hours of dissection laboratory during their first year.
      According to the survey responses, they generally considered these durations to
      be adequate for achieving their anatomy education goals. Almost all the students
      regarded the dissection laboratory as an essential and most helpful modality.
      Thus, we suggest that these ranges of time along with cadaver dissection could be
      useful guidelines for optimized anatomy education. The survey data also indicated
      that a more clinically oriented anatomy education could improve students'
      results. 

PMID- 23869264
TI  - Rare multiple variations in brachial plexus and related structures in the left
      upper limb of a Dravidian male cadaver.
AB  - Anatomical variations of the nerves, muscles, and vessels in the upper limb have
      been described in many anatomical studies; however, the occurrence of 6
      variations in an ipsilateral limb is very rare. These variations occur in the
      following structures: the pectoralis minimus muscle, the communication between
      the external jugular vein and cephalic vein, axillary arch, the Struthers
      ligament, the medial, lateral, and posterior cords of the brachial plexus, and
      the common arterial trunk from the third part of the axillary artery. The
      relationship of these variations to each other and their probable clinical
      presentation is discussed. 

PMID- 23869265
TI  - Right-sided aortic arch with the retroesophageal left subclavian artery as the
      fourth branch.
AB  - We present a rare variation of the right-sided aortic arch with the
      retroesophageal left subclavian artery as the forth branch found in a cadaver of
      an 89-year-old Korean woman during a routine dissection. In this case, the first
      branch that arose from the ascending aorta was the left common carotid artery,
      which crossed ventral to the trachea in a left cephalic direction, followed by
      the right common carotid artery and then the right subclavian artery. Distal to
      these branches the aortic arch ran dorsally, passing between the esophagus and
      the vertebra. The left subclavian artery arose from the descending portion of the
      aortic arch, crossing over to the left upper extremity behind the esophagus. This
      anomaly was not accompanied by congenital heart disease. Accurate information
      regarding this variation is of great importance to surgeons for its early
      identification and preservation during interventions and to radiologists for
      precise interpretation of angiograms. 

PMID- 23869266
TI  - The Measurement of Intra-abdominal Pressure in Awake Rat Cystometry.

PMID- 23869267
TI  - The Role of Intra-abdominal Pressure Measurement in Awake Rat Cystometry.
AB  - Rat cystometry is increasingly being used in research on overactive bladder and
      is a research tool for investigating bladder functions during the storage and
      voiding phases. Measurement of the pressure in the bladder is an essential part
      of cystometry, although that pressure is the sum of both detrusor and intra
      abdominal pressures. In anesthetic cystometry, measurement of the intra-abdominal
      pressure is not necessary, because the values of this variable are negligible. In
      awake cystometry, however, it is mandatory to separate the changes in intra
      abdominal pressure from those in intravesical pressure, because consciousness
      causes much variability in intra-abdominal pressure. This review describes why we
      use the term "detrusor overactivity" in animal research with intra-abdominal
      pressure and presents evidence for the role of intra-abdominal pressure in the
      cystometry of normal rats and in animal models of overactive bladder directed at
      understanding the pathogenesis of the overactive bladder condition. The
      methodology is also briefly reviewed. 

PMID- 23869268
TI  - Pain, catastrophizing, and depression in chronic prostatitis/chronic pelvic pain
      syndrome.
AB  - Persistent and disabling pain is the hallmark of chronic prostatitis/chronic
      pelvic pain syndrome (CP/CPPS). However, disease severity (as measured by
      objective indexes such as those that use radiography or serology) is only
      marginally related to patients' reports of pain severity, and pain-related
      presentation can differ widely among individuals with CP/CPPS. Increasing
      evidence in support of the biopsychosocial model of pain suggests that cognitive
      and emotional processes are crucial contributors to inter-individual differences
      in the perception and impact of pain. This review describes the growing body of
      literature relating depression and catastrophizing to the experience of pain and
      pain-related sequelae in CP/CPPS. Depression and catastrophizing are consistently
      associated with the reported severity of pain, sensitivity to pain, physical
      disability, poor treatment outcomes, and inflammatory disease activity and
      potentially with early mortality. A variety of pathways, from cognitive to
      behavioral to neurophysiological, seem to mediate these deleterious effects.
      Collectively, depression and catastrophizing are critically important variables
      in understanding the experience of pain in patients with CP/CPPS. Pain,
      depression, and catastrophizing might all be uniquely important therapeutic
      targets in the multimodal management of a range of such conditions. 

PMID- 23869269
TI  - Transurethral procedures for lower urinary tract symptoms resulting from benign
      prostatic enlargement: a quality and meta-analysis.
AB  - PURPOSE: Thanks to advancements in surgical techniques and instruments, many
      surgical modalities have been developed to replace transurethral resection of the
      prostate (TURP). However, TURP remains the gold standard for the surgical
      treatment of benign prostatic hyperplasia (BPH). We conducted a meta-analysis on
      the efficacy and safety of minimally invasive surgical therapies for BPH compared
      with TURP. METHODS: This meta-analysis used a Medline search assessing the period
      from 1997 to 2011. A total of 784 randomized controlled trials were identified in
      an electronic search. Among the 784 articles, 36 randomized controlled trials
      that provided the highest level of evidence (level 1b) were included in the meta
      analysis. We also conducted a quality analysis of selected articles. RESULTS:
      Only 2 articles (5.56%) were assessed as having a low risk of bias by use of the
      Cochrane collaboration risk of bias tool. On the other hand, by use of the Jadad
      scale, there were 26 high-quality articles (72.22%). Furthermore, 28 articles
      (77.78%) were assessed as high-quality articles by use of the van Tulder scale.
      Holmium laser enucleation of the prostate (HoLEP) showed the highest reduction of
      the International Prostate Symptom Score compared with TURP (P<0.0001). Bipolar
      TURP, bipolar transurethral vaporization of the prostate, HoLEP, and open
      prostatectomy showed superior outcome in postvoid residual urine volume and
      maximum flow rate. The intraoperative complications of the minimally invasive
      surgeries had no statistically significant inferior outcomes compared with TURP.
      Also, there were no statistically significant differences in any of the
      modalities compared with TURP. CONCLUSIONS: The selection of an appropriate
      surgical modality for BPH should be assessed by fully understanding each
      patient's clinical conditions.

PMID- 23869270
TI  - Increased bladder wall thickness in diabetic and nondiabetic women with
      overactive bladder.
AB  - PURPOSE: Bladder wall thickness has been reported to be associated with
      overactive bladder (OAB) in women. Diabetic women have an increased risk for OAB
      syndrome and may have an increased risk for bladder wall thickness. METHODS: A
      total of 235 female patients aged 40 to 75 years were categorized into four
      groups. The first group consisted of women free of urgency or urge urinary
      incontinence. The second group included nondiabetic women with idiopathic OAB.
      The third group consisted of women with diabetes and clinical OAB, and women with
      diabetes but without OAB constituted the fourth group. Bladder wall thickness at
      the anterior wall was measured by ultrasound by the suprapubic approach with
      bladder filling over 250 mL. RESULTS: The diabetic (third group) and nondiabetic
      (second group) women with OAB had significantly greater bladder wall thickness at
      the anterior bladder wall than did the controls. However, the difference was not
      significant between the diabetic (third group) and the nondiabetic (second group)
      women with OAB. Women with diabetes but without OAB (fourth group) had greater
      bladder wall thickness than did the controls but this difference was not
      significant. Additionally, the difference in bladder wall thickness between
      diabetic women with (third group) and without (fourth group) OAB was not
      significant. CONCLUSIONS: This is the first study to show that bladder wall
      thickness is increased in diabetic women with and without OAB. Additionally,
      nondiabetic women with OAB had increased bladder wall thickness. Further studies
      may provide additional information for diabetic and nondiabetic women with OAB,
      in whom the etiopathogenesis of the disease may be similar.

PMID- 23869271
TI  - Free prostate-specific antigen provides more precise data on benign prostate
      volume than total prostate-specific antigen in korean population.
AB  - PURPOSE: To investigate the efficacy of total prostate-specific antigen (tPSA)
      and free prostate-specific antigen (fPSA) for the estimation of prostate volume
      (PV) in pathologically-proven benign prostatic hyperplasia (BPH) patients.
      METHODS: From January 2010 to March 2013, 165 Korean men with a PSA less than 10
      ng/mL who were diagnosed without prostate cancer by prostate biopsy were
      enrolled. Patients were classified into three age groups: <=60, 61-70, and >70
      years old. The results were organized to estimate and compare the ability of
      serum tPSA and fPSA to assess the PV. RESULTS: Enrolled patients had a median age
      of 63.5 years (44 to 80), a median tPSA of 5.72 ng/mL, a median fPSA of 0.98
      ng/mL and a median PV of 53.68 mL, respectively. Among the associations between
      tPSA, fPSA, age, and PV, the highest correlation was verified between fPSA and PV
      (r=0.377, P<0.0001); the correlation coefficient between tPSA and PV was much
      lower (r=0.262, P<0.001). All stratified age cohorts showed the same findings.
      The ROC curves (for PV greater than 30, 40, and 50 mL) showed that fPSA (area
      under the curve [AUC]=0.781, 0.718, and 0.700) outperformed tPSA (AUC=0.657,
      0.583, and 0.67) in its ability to predict clinically significant PV enlargement.
      CONCLUSION: Both tPSA and fPSA significantly correlated with PV in Korean men,
      while the correlation efficiency between fPSA and PV was more powerful. fPSA may
      be a useful tool in making therapeutic decisions and follow-up management in BPH
      patients.

PMID- 23869272
TI  - Effect of low-dose triple therapy using gabapentin, amitriptyline, and a
      nonsteroidal anti-inflammatory drug for overactive bladder symptoms in patients
      with bladder pain syndrome.
AB  - PURPOSE: Patients with bladder pain syndrome/interstitial cystitis (BPS/IC) can
      have pain as a main symptom and overactive bladder (OAB) symptoms that are
      directly or indirectly related to a major mechanism that causes pain. The primary
      purpose of this study is firstly to identify the prevalence rate of OAB symptoms
      in patients with BPS/IC, secondly to identify changes in OAB symptoms after low
      dose triple therapy, and thirdly to build a theoretical foundation to improve
      quality of life for patients. METHODS: Patients who met the inclusion criteria of
      BPS/IC through basic tests including the O'Leary-Sant symptom index, overactive
      bladder symptom score (OABSS), and visual analog scale (VAS) were identified.
      Treatment-based changes in OAB symptoms were identified using the IC Symptom
      Index and IC Problem Index (ICSI/ICPI), OABSS, and VAS before, and 4 and 12 weeks
      after low-dose triple therapy. RESULTS: The patients consisted of 3 men and 20
      women, and their mean age was 61.9 years (41.0-83.2 years). Comparing values
      before treatment, and 4 and 12 weeks after treatment (baseline vs. 4 weeks to
      baseline vs. 12 weeks), the rates of improvement were as follows: ICSI, 44.2% to
      63.7%; ICPI, 46.9% to 59.4%; OABSS, 34.3% to 58.2%; and VAS, 53.6% to 75.0%,
      which showed statistically significant differences (P<0.05). However, comparing
      values at 4 and 12 weeks after treatment (4 weeks vs. 12 weeks), the ICSI and VAS
      showed a statistically significant decrease (P<0.05). The ICPI and OABSS showed
      slight improvement, but no statistically significant differences (P>0.05).
      CONCLUSIONS: Low-dose triple therapy in BPS/IC results in a clear decrease in OAB
      symptoms in the first 4 weeks after treatment, and additional treatment for 8
      weeks had a partial effect with varied statistical significances depending on the
      questionnaires.

PMID- 23869273
TI  - Preoperative factors affecting postoperative early quality of life during the
      learning curve of holmium laser enucleation of the prostate.
AB  - PURPOSE: The aim of this study was to investigate the preoperative factors
      related to early quality of life (QoL) in patients with benign prostatic
      hyperplasia after holmium laser enucleation of the prostate (HoLEP) during the
      surgeon's learning curve. METHODS: The medical records of 82 patients with a
      follow-up period of at least 3 months who were treated with HoLEP during the time
      of a surgeon's learning curve were analyzed retrospectively. We divided the
      patients into two groups on the basis of the QoL component of the International
      Prostate Symptom Score (IPSS) 3 months after HoLEP: the high QoL group
      (IPSS/QoL<=3) and the low QoL group (IPSS/QoL>=4). Preoperative factors in each
      group were compared, including prostate volume, prostate-specific antigen,
      history of acute urinary retention (AUR), urgency incontinence, IPSS, and
      urodynamic parameters. Detrusor underactivity was defined as a bladder
      contractility index less than 100 on urodynamic study. RESULTS: A total of 61
      patients (74.3%) had a high QoL, whereas 21 (25.7%) had a low QoL. A history of
      AUR, detrusor pressure on maximal flow (PdetQmax), bladder outlet obstruction
      grade, bladder contractility index, and detrusor underactivity were associated
      with postoperative QoL in the univariate analysis. In the multivariate analysis,
      a history of AUR and PdetQmax were independent factors affecting postoperative
      QoL. CONCLUSIONS: A history of AUR and bladder contractility affect early QoL,
      and preoperative urodynamic study plays an important role in the proper selection
      of patients during the HoLEP learning curve.

PMID- 23869274
TI  - Migration of a Hem-o-Lok Clip to the Ureter Following Laparoscopic Partial
      Nephrectomy Presenting With Lower Urinary Tract Symptoms.
AB  - We report a case of ureteral migration of a surgical clip after partial
      nephrectomy in which the clip was misdiagnosed as a ureteral stone. A 37-year-old
      woman had undergone laparoscopic partial nephrectomy of right renal cell
      carcinoma at another hospital 2 years previously. Postoperatively, she had
      gradually acquired lower urinary tract symptoms. Then, she complained of sudden
      right flank pain for a week. A plain X-ray and enhanced abdominopelvic computed
      tomography scan were performed. A 0.5 cm*1.0 cm right upper ureteral opacity with
      borderline hydronephrosis was seen but could not be found on the X-ray.
      Ureteroscopy revealed a medium-sized Hem-o-Lok clip on the right upper ureter
      that was removed with a stone basket. We concluded that a Hem-o-Lok clip used for
      collecting system sealing had migrated to the ureter and had been misdiagnosed as
      a ureteral stone on a computed tomography scan. 

PMID- 23869275
TI  - Ureteral penetration caused by drilling during internal pelvic bone fixation:
      delayed recognition.
AB  - A 49-year-old man was referred to our department with profuse serous fluid
      discharge from a Penrose drain after undergoing internal fixation with metal
      screws for multiple pelvic bone fractures. A definite ureteral penetration was
      identified that was orientated from the lateral to the medial aspect of the right
      distal ureter. The patient was surgically treated with excision of the 2-cm
      injured ureteral segment, end-to-end ureteroureterostomy, and double J ureteral
      stent placement. To our knowledge, a penetrating ureteral injury caused by bone
      drilling has not been reported previously in the published literature. This case
      shows that surgeons who do pelvic surgery, including orthopedic surgeons, should
      be familiar with the anatomical relationship of the ureter and its potential
      injuries. 

PMID- 23869276
TI  - The use of IV-tubing as a closed-suction drainage system during neurosurgical
      cases in Tanzania.
AB  - BACKGROUND: Commercial closed-suctions drainage systems are commonly used in the
      United States and many other countries for use in neurosurgical cases. However,
      in Tanzania and other developing nations with fewer resources, these are not
      available. This report explores another option for a closed-system drainage
      system utilizing inexpensive supplies found commonly in hospitals around the
      world. METHODS: Sterile IV-tubing is cut, inserted into the wound, and brought
      out through an adjacent puncture incision. For suction, an empty plastic bottle
      can be attached to the tubing. RESULTS: The IV-tubing closed-suction drainage
      system was applied in both cranial and spinal neurosurgical procedures, including
      as subdural, subgaleal, epidural, and suprafacial drains. It maintained suction
      and was an adequate substitute when commercial drains are unavailable.
      CONCLUSIONS: This report illustrates how sterile IV-tubing can be adapted for use
      as a closed-drainage system. It utilizes inexpensive supplies commonly found in
      many hospitals throughout the world and can be applied to both cranial and spinal
      neurosurgical procedures.

PMID- 23869277
TI  - Survival of child after lion attack.
AB  - BACKGROUND: Injuries to humans caused by attacks from large predators are very
      rare, especially in the United States, Europe, or Latin America. A few cases were
      reported on accidents in zoos or animal farms, being very uncommon in children.
      The purposes of this report include describing the case of a child who sustained
      an attack by a lion named "Bang-Bang", which resulted in injuries to the head,
      chest, and abdomen, as well as the subsequent neurosurgical treatment and
      providing a review of the literature. CASE DESCRIPTION: We report the case of an
      8-year-old boy who was attacked by a lion during a circus show. The patient
      underwent an emergent neurosurgical procedure, including parietal craniectomy,
      cleaning, and extensive surgical debridement of the wounds. Despite open severe
      head trauma with brain damage as well as thorax and abdomen trauma, the child
      survived, with minimal neurological sequelae. CONCLUSIONS: Human injury resulting
      from encounters with nondomesticated animals is increasingly rising throughout
      the world. This case highlights the potentially violent and aggressive nature of
      wild mammals held in captivity. Unusual wild animal attacks and the complex
      injuries that result may pose a challenge to surgeons practicing in resource
      limited settings. In this sense, the best treatment in the mentioned case is the
      prevention of human injuries by these animals. In addition, to attend to these
      infrequent cases, the authors emphasize the importance of a multidisciplinary
      approach to achieve the best cosmetic and functional results.

PMID- 23869278
TI  - Minimally invasive surgical decompression for lumbar spinal metastases.
AB  - BACKGROUND: The risk of significant morbidity and mortality often outweighs the
      benefit of surgical resection as palliative treatment for patients with high
      systemic disease burden, poor cardiopulmonary status, and previous spinal
      surgeries. Minimally invasive surgical (MIS) approaches to decompressing
      metastatic epidural cord compression (MECC) can address these issues and thereby
      make palliation a feasible option for these patients. CASE DESCRIPTION: We
      present the cases of three consecutively collected patients with severe
      neurological compromise secondary to lumbar epidural metastases who underwent MIS
      decompression and achieved improved functional outcome and quality of life. The
      first patient is a 23-year-old female with metastatic Ewing's sarcoma who
      presented with 2 weeks of a right foot drop and radiculopathic pain. The next
      case is that of a 71-year-old male with metastatic prostate cancer who presented
      with significant radiculopathic L5-S1 pain and severe motor deficits in his lower
      extremities. The last case is that of a 73-year-old male with metastatic
      hepatocellular carcinoma who presented with worsening left leg weakness,
      paresthesia, and dysethesia. Postoperatively, each patient experienced
      significant improvement and almost complete enduring return of function,
      strength, and resolution of pain. CONCLUSION: We demonstrate that MIS approaches
      to spinal decompression as palliative treatment for metastatic disease is a
      viable treatment in patients with a focal symptomatic lesion and comes with the
      benefits of decreased surgical morbidity inherent to the minimally invasive
      approach as well as excellent functional outcomes.

PMID- 23869279
TI  - Rapidly progressing monoparesis caused by Chiari malformation type I without
      syringomyelia.
AB  - BACKGROUND: Patients with Chiari malformation type I (CM-I) can manifest
      neurological symptoms, such as headache, neck pain, dysesthesia, swallowing
      disturbance, and paresis, which are usually stable or slowly progressive even if
      syringomyelia is coexistent. In some instances, however, acute onset of
      neurological symptoms has been reported but the pathogenetic mechanism and
      subsequent clinical course have not been explained. In those cases, it was
      reported that urgent treatment of foramen magnum decompression (FMD) was very
      effective. This work reports that an 11-year-old girl with CM-I subacutely
      developed unique symptoms and that urgent treatment of FMD was very effective.
      CASE DESCRIPTION: We present here an 11-year-old girl with CM-I who subacutely
      developed dysphagia, left upper extremity monoparesis and sensory dysesthesia,
      with the limb assuming a peculiar posture at rest, with the wrist in extension
      and the elbow joint in flexion. Although her symptoms were assumed to be due to
      previously diagnosed CM-I without syringomyelia, no differences on magnetic
      resonance imaging (MRI) could be found except for slight change in the shape of
      tonsils compared with the previous ones. FMD and C1 removal with duraplasty was
      performed and resulted in an excellent neurological recovery. CONCLUSION: This
      case is a reminder that the presence of a new neurological deficit referable to
      nuclei within, or tracts that traverse, the cerebromedullary junction is a firm
      surgical indication for FMD in a patient with CM-I. MRI was nearly identical
      during the asymptomatic and symptomatic periods in this case, and did not explain
      the timing of symptom onset.

PMID- 23869280
TI  - Traumatic rupture of an intracranial dermoid cyst: Case report and literature
      review.
AB  - BACKGROUND: Dermoid tumors are benign congenital cystic lesions that usually
      present with local mass effect. Very rarely, they present as spontaneous
      ruptures. Traumatic rupture of these dermoid cysts is an extremely rare event and
      only a handful of such cases have been ever reported. CASE DESCRIPTION: A 47-year
      old female presented to our hospital with a ruptured intracranial dermoid cyst
      following a mild head injury. The ruptured cyst contents were disseminated into
      the subarachnoid and intraventricular compartments, resulting in an obstructive
      hydrocephalus. After medical stabilization, she underwent gross total resection
      of the cyst using combined transsylvian, transcortical-transventricular, and sub
      frontal approaches. A ventriculo-peritoneal shunt was eventually also needed.
      CONCLUSION: Traumatic rupture of an intracranial dermoid cyst is an extremely
      rare event and this is only the fourth such case reported in the literature. We
      presume that this rupture occurs due to sudden shifts in the cyst sac, which is
      adherent to some partially mobile intracranial contents. Although computed
      tomography (CT) is often adequate in making a diagnosis of this entity, magnetic
      resonance imaging (MRI) provides complete characterization of the extent of lipid
      dissemination, and is essential for operative planning. Intravenous steroids at
      presentation are helpful in managing the aseptic meningitis associated with
      rupture. Complete surgical resection is the goal, but must be weighed against the
      risk for injury to nearby vital structures. Hydrocephalus should be managed
      promptly, and patients should be monitored for it closely in the perioperative
      period. Even though the recurrence rate with subtotal resection is extremely
      rare, follow up should be done routinely.

PMID- 23869281
TI  - Migration of traumatic intracranial subdural hematoma to lumbar spine causing
      radiculopathy.
AB  - BACKGROUND: There have been rare reports of intracranial subdural hematoma (SDH)
      that migrated into the spine. All previous cases have been surgically managed and
      in this case report, we describe the first case of conservatively managed spinal
      hematoma secondary to migratory intracranial SDH. CASE DESCRIPTION: A 26-year-old
      male presented with a left tentorial SDH after blunt trauma. He was
      conservatively managed and discharged home. He presented 8 days later with
      worsening lower back pain that was found to be secondary to a spinal SDH.
      CONCLUSION: Spinal hematomas can be a serious sequelae of migrated intracranial
      hematomas. Tentorial and other caudally located intracranial hematomas may be
      more prone to this phenomenon.

PMID- 23869282
TI  - Cellular myxoma of the lumbar spine.
AB  - BACKGROUND: Cellular myxoma is a histopathologically distinctive benign neoplasm,
      which has often been categorized among the broad category of benign mesenchymal
      tumors with myxoid stroma and fibroblast- and/or myofibroblast-like cells. These
      tumors can arise in any of the large muscles and are usually found in the thigh,
      shoulder, buttocks, and upper arm, and more rarely in the head and neck or in
      small muscles of the hand. CASE DESCRIPTION: Here we illustrate the case of a 57
      year-old female with a spinal lesion, who initially presented with complaints of
      vague pelvic discomfort but no focal neurological deficits. Imaging revealed a
      sharply demarcated paraspinal lesion concerning for a tumorous growth. The lesion
      was excised in toto and a detailed immuno-histopathological analysis was
      performed revealing the diagnosis of a cellular myxoma. Postoperative imaging
      showed a gross total resection and the patient is under clinical surveillance
      since, with no signs of recurrence after 42 months. CONCLUSION: Although very
      rare, this entity should be considered in the differential diagnosis of any
      spinal and paraspinal mass to allow for adequate treatment, which requires wide
      excision with clean margins to avoid any local recurrence.

PMID- 23869283
TI  - Chronic subdural hematomas and the elderly.

PMID- 23869284
TI  - RE: Reasons, procedures, and outcomes in ventriculoatrial shunts: A single-center
      experience.

PMID- 23869285
TI  - Cerebral venous sinus thrombosis complicated by subdural hematomas: Case series
      and literature review.
AB  - BACKGROUND: Cerebral venous sinus thrombosis (CVST) can cause elevated
      intracranial pressure, hemorrhagic venous infarct, and cortical subarachnoid
      hemorrhage. We present a case series and literature review to illustrate that
      CVST can also present with subdural hematoma (SDH). CASE DESCRIPTION: Chart
      review was completed on a retrospective case series of CVST with spontaneous SDH.
      We also conducted a literature search. Over a 6 year interval, three patients
      with CVST and SDH were admitted to the neurointensive care unit. A 38-year-old
      woman had both SDH and a hemorrhagic venous infarct associated with a transverse
      sinus thrombosis. She was managed conservatively with long-term anticoagulation.
      A 68-year-old woman presented with an acute SDH requiring craniotomy and a
      thrombosed cortical vein was noted intraoperatively. Computed tomography
      venography showed thrombosis of the superior sagittal sinus. She had polycythemia
      vera with the V617 Jak2 gene mutation and was managed with aspirin and
      hydroxyurea. A 60-year-old male had recurrence of a spontaneous convexity SDH
      requiring reoperation. Neuroimaging identified ipsilateral transverse sinus
      thrombosis with retrograde flow into the opposite sinus. Manometry demonstrated
      elevated venous pressures and these normalized after thrombectomy. Angiography
      performed after endovascular treatment demonstrated a normal venous drainage
      pattern. There have been limited reports of SDH complicating CVST in the
      literature. CONCLUSION: This case series and literature review demonstrates that
      CVST can also present with spontaneous SDH with or without associated venous
      infarctions. Treatment must be individualized. This is the first published
      description of endovascular thrombectomy for recurrent symptomatic SDH due to
      CVST.

PMID- 23869287
TI  - Nonparametric Diagnostic Test for Conditional Logistic Regression.
AB  - The use of conditional logistic regression models to analyze matched case-control
      data has become standard in statistical analysis. However, methods to test the
      fit of these models has primarily focused on influential observations and the
      presence of outliers, while little attention has been given to the functional
      form of the covariates. In this paper we present methods to test the functional
      form of the covariates in the conditional logistic regression model, these
      methods are based on nonparametric smoothers. We assess the performance of the
      proposed methods via simulation studies and illustrate an example of their use on
      data from a community based intervention.

PMID- 23869288
TI  - Racial and Ethnic Profiles of Complementary and Alternative Medicine Use Among
      Young Adults in the United States: Findings From the National Longitudinal Study
      of Adolescent Health.
AB  - This study describes complementary and alternative medicine use among a national
      sample of young adults, with an emphasis on characterizing racial and ethnic
      differences, highlighting variation across subgroups of Hispanics. The authors
      examined young adults ages 18 to 27 years (n = 14 128) from wave III (2001-2002)
      of the National Longitudinal Study of Adolescent Health. Prevalence estimates and
      logistic regression results were weighted and adjusted for complex sample design.
      The study examined recent complementary and alternative medicine use in the past
      12 months, recent use for each of 15 specific complementary and alternative
      medicine modalities, and the 5 most commonly used modalities (herbs, massage,
      chiropractic, relaxation, and vitamins). Results showed that 29% of young adults
      aged 18 to 27 years recently used complementary and alternative medicine.
      Prevalence was highest among Cuban Americans (42%) and lowest among blacks (22%).
      Young adults used a diversity of complementary and alternative medicine
      modalities and there were substantial differences in use across racial and ethnic
      groups.

PMID- 23869290
TI  - The dirty dozen of diabetes.

PMID- 23869289
TI  - TSH - Clinical Aspects of its Use in Determining Thyroid Disease in the Elderly.
      How Does it Impact the Practice of Medicine in Aging?
AB  - The last four decades have seen enormous growth in the efficacy of serum thyroid
      stimulating hormone (thyrotropin, TSH) assay methodology, establishing TSH as the
      hallmark of thyroid testing. At the center of the considerations is the strong
      inverse correlation between serum thyrotropin and free thyroxine concentrations.
      While it is widely accepted that elevated serum TSH concentrations are consistent
      with thyroid dysfunction, a vast multitude of additional factors must be
      considered before an accurate clinical diagnosis can be made followed by an
      appropriate treatment. Epidemiological studies have demonstrated slightly
      elevated serum TSH concentrations among the elderly population. There is,
      however, a debate whether these elevated TSH levels reflect an increased
      prevalence of hypothyroidism among the elderly or a normal aspect of healthy
      aging. A comprehensive analysis of the many variables associated with this debate
      and TSH measurement as a diagnostic tool in aging should provide insight into the
      clinical efforts to diagnose and treat thyroid disease, particularly in the
      elderly population.

PMID- 23869291
TI  - Pioglitazone: A prudent prescription.

PMID- 23869292
TI  - Prenatal treatment of mothers with fetuses at risk for congenital adrenal
      hyperplasia: How relevant is it to Indian context?
AB  - Management of congenital adrenal hyperplasia (CAH) from embryonic stage to
      adulthood is a critical challenge. We would like to comment on some of the
      practical difficulties in offering prenatal treatment for CAH-affected fetuses in
      Indian population. For initiating the prenatal dexamethasone (DEX) treatment, all
      members of the family need to be informed about the risks and benefits of the
      treatment to the mother and the fetus as well as about the available invasive
      diagnostic tests to determine the gender and genotype of the fetus. Prenatal sex
      disclosure is not routinely practiced in India due to high female feticide rate.
      The treatment has to be given to both unaffected and affected female fetuses
      until the determination of prenatal sex. Moreover, most of our populations reside
      in rural areas where the antenatal care is not adequate. Prenatal DEX treatment
      in India outruns the risks rather than the benefits, as evident from the
      literature on the safety of pregnant mothers and fetuses. 

PMID- 23869286
TI  - The history of pathology informatics: A global perspective.
AB  - Pathology informatics has evolved to varying levels around the world. The history
      of pathology informatics in different countries is a tale with many dimensions.
      At first glance, it is the familiar story of individuals solving problems that
      arise in their clinical practice to enhance efficiency, better manage (e.g.,
      digitize) laboratory information, as well as exploit emerging information
      technologies. Under the surface, however, lie powerful resource, regulatory, and
      societal forces that helped shape our discipline into what it is today. In this
      monograph, for the first time in the history of our discipline, we collectively
      perform a global review of the field of pathology informatics. In doing so, we
      illustrate how general far-reaching trends such as the advent of computers, the
      Internet and digital imaging have affected pathology informatics in the world at
      large. Major drivers in the field included the need for pathologists to comply
      with national standards for health information technology and telepathology
      applications to meet the scarcity of pathology services and trained people in
      certain countries. Following trials by a multitude of investigators, not all of
      them successful, it is apparent that innovation alone did not assure the success
      of many informatics tools and solutions. Common, ongoing barriers to the
      widespread adoption of informatics devices include poor information technology
      infrastructure in undeveloped areas, the cost of technology, and regulatory
      issues. This review offers a deeper understanding of how pathology informatics
      historically developed and provides insights into what the promising future might
      hold. 

PMID- 23869294
TI  - Methodology and feasibility of a structured education program for diabetes
      education in India: The National Diabetes Educator Program.
AB  - India has over 62 million people with diabetes. Unfortunately, there are no
      trained diabetes educators in India although many are self-taught through
      experience. The National Diabetes Educator Program (NDEP) was initiated with the
      primary aim to educate and train diabetes educators in India. The first cycle of
      NDEP was conducted during the period June 2011 to March 2012 in 96 training
      centers in India and trained 1032 diabetes educators mainly drawn from various
      diabetes clinics across the country. Structured modules were taught by
      diabetologists/endocrinologists or experienced educators. A majority of the
      trainees attended all sessions and 95% of the trainees acknowledged that the
      program met its objective and was beneficial to them. This article elaborates the
      methodology of the program and its evaluation based on feedback received from the
      participants and trainers. 

PMID- 23869293
TI  - National recommendations: Psychosocial management of diabetes in India.
AB  - Although several evidence-based guidelines for managing diabetes are available,
      few, if any, focus on the psychosocial aspects of this challenging condition. It
      is increasingly evident that psychosocial treatment is integral to a holistic
      approach of managing diabetes; it forms the key to realizing appropriate
      biomedical outcomes. Dearth of attention is as much due to lack of awareness as
      due to lack of guidelines. This lacuna results in diversity among the standards
      of clinical practice, which, in India, is also due to the size and complexity of
      psychosocial care itself. This article aims to highlight evidence- and experience
      based Indian guidelines for the psychosocial management of diabetes. A systemic
      literature was conducted for peer-reviewed studies and publications covering
      psychosocial aspects in diabetes. Recommendations are classified into three
      domains: General, psychological and social, and graded by the weight they should
      have in clinical practice and by the degree of support from the literature.
      Ninety-four recommendations of varying strength are made to help professionals
      identify the psychosocial interventions needed to support patients and their
      families and explore their role in devising support strategies. They also aid in
      developing core skills needed for effective diabetes management. These
      recommendations provide practical guidelines to fulfill unmet needs in diabetes
      management, and help achieve a qualitative improvement in the way physicians
      manage patients. The guidelines, while maintaining an India-specific character,
      have global relevance, which is bound to grow as the diabetes pandemic throws up
      new challenges. 

PMID- 23869295
TI  - Implications of serum paraoxonase activity in obesity, diabetes mellitus, and
      dyslipidemia.
AB  - Human serum paraoxonase 1 (PON1) is an enzyme with esterase activity, and is
      physically bound to high-density lipoproteins (HDL). It plays a key role in the
      action of HDL toward protection of lipoprotein and biological membrane against
      oxidative damage. It may have a protective role against atherosclerosis by virtue
      of its action on hydrolyzing lipid peroxides and preventing accumulation of
      phospholipids in oxidized low-density lipoprotein (LDL). PON1 is hypothesized to
      be an indicator of the risk of atherosclerosis and coronary artery disease
      development. Numerous studies have implicated PON1 activity in relation to
      various endocrine disorders. The current article reviews the clinical
      perspectives of PON1 activity with regards to obesity, diabetes mellitus with its
      complications, and dyslipidemia. 

PMID- 23869296
TI  - Glucagon-like peptide-1 analogues: An overview.
AB  - Abnormalities of the incretin axis have been implicated in the pathogenesis of
      type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) and gastroinhibitory
      intestinal peptide constitutes >90% of all the incretin function. Augmentation of
      GLP-1 results in improvement of beta cell health in a glucose-dependant manner
      (post-prandial hyperglycemia) and suppression of glucagon (fasting
      hyperglycemia), amongst other beneficial pleiotropic effects. Native GLP-1 has a
      very short plasma half-life and novel methods have been developed to augment its
      half life, such that its anti-hyperglycemic effects can be exploited. They can be
      broadly classified as exendin-based therapies (exenatide, exenatide once weekly),
      DPP-4-resistant analogues (lixisenatide, albiglutide), and analogues of human GLP
      1 (liraglutide, taspoglutide). Currently, commercially available analogues are
      exenatide, exenatide once weekly, and liraglutide. This review aims to provide an
      overview of most GLP-1 analogues. 

PMID- 23869297
TI  - A fish a day, keeps the cardiologist away! - A review of the effect of omega-3
      fatty acids in the cardiovascular system.
AB  - Dyslipidemia and its consequences are emerging as epidemics with deleterious
      consequences on cardiovascular (CV) health. The beneficial effects of omega-3
      fatty acids on cardiac and extra cardiac organs have been extensively studied in
      the last two decades, and continue to show great promise in the primary and
      secondary prevention of cardiovascular diseases (CVDs). Omega-3-fatty acid
      supplementation has been proven to have beneficial action on lipid profile,
      cytokine cascade, oxidant-anti-oxidant balance, parasympathetic and sympathetic
      tone and nitric oxide synthesis. This review summarizes the current knowledge on
      the basis of its cardiac and non-cardiac benefits, present results from clinical
      trials and the recommendations for its use in cardiac diseases and dyslipidemias.

PMID- 23869299
TI  - Complicated urinary tract infections associated with diabetes mellitus:
      Pathogenesis, diagnosis and management.
AB  - Diabetes mellitus has a number of long-term effects on the genitourinary system.
      These effects predispose to bacterial urinary tract infections (UTIs) in the
      patient with diabetes mellitus. Complicated UTIs are also common and potentially
      life-threatening conditions. They include emphysematous pyelonephritis,
      emphysematous pyelitis/cystitis, xanthogranulomatous pyelonephritis,
      renal/perirenal abscess, and renal papillary necrosis. Improved outcomes of these
      entities may be achieved by early diagnosis, knowledge of common predisposing
      factors, appropriate clinical and radiological assessment, and prompt management.
      Herein we review complicated UTIs associated with diabetes mellitus in terms of
      pathogenesis, clinical manifestations, radiological features, and current
      management options. 

PMID- 23869298
TI  - Molecular diagnosis of maturity onset diabetes of the young in India.
AB  - Diabetes is highly prevalent in India and the proportion of younger patients
      developing diabetes is on the increase. Apart from the more universally known
      type 1 diabetes and obesity related type 2 diabetes, monogenic forms of diabetes
      are also suspected to be prevalent in many young diabetic patients. The
      identification of the genetic basis of the disease not only guides in therapeutic
      decision making, but also aids in genetic counselling and prognostication.
      Genetic testing may establish the occurrence and frequency of early diabetes in
      our population. This review attempts to explore the utilities and horizons of
      molecular genetics in the field of maturity onset diabetes of the young (MODY),
      which include the commoner forms of monogenic diabetes. 

PMID- 23869300
TI  - Transcriptomic analysis of visceral adipose from healthy and diabetic obese
      subjects.
AB  - Understanding the role of visceral fat accumulation in the occurrence and
      progression of metabolic syndrome is of considerable interest. In order to
      understand the difference between visceral tissue biology of healthy and
      unhealthy obese individuals, we have used microarray profiling to compare genome
      wide expression differences between visceral adipose tissue biopsies obtained
      from obese diabetics, and those from age and body mass index (BMI) matched normal
      glucose tolerance subjects. Whereas genes upregulated in diabetics showed
      enrichment of natural killer cell mediated cytotoxicity, the downregulated genes
      showed enrichment of biosynthesis of unsaturated fatty acids. Given the known
      inhibitory effect of unsaturated fatty acids on inflammation and natural killer
      cell number or activity, our results suggest that visceral inflammation resulting
      from decreased levels of unsaturated fatty acids may underlie progression of
      diabetes in obese individuals. 

PMID- 23869301
TI  - The curious case of Sudyumna: A tale of sex reversal from the Bhagavata Purana.
AB  - Tracking endocrine disease in mythology especially one as old and diverse as
      Indian mythology is a challenge. A curious case of sex reversal in the bhagavata
      purana is described and hunches about the disorder of sexual differentiation that
      manifested itself in the hapless Sudyumna the son of Manu is attempted. 5 alpha
      reductase deficiency appears to be the closest candidate but some twists in the
      tale are required to fill in the gaps. 

PMID- 23869302
TI  - Prevalence, clinical and biochemical profile of subclinical hypothyroidism in
      normal population in Mumbai.
AB  - BACKGROUND: Subclinical Hypothyroidism (ScHt) affects 3-15% of the adult
      population. It's clinical and biochemical profile is not well defined, especially
      in Indian scenario. Our study aimed at screening normal population to define
      normative ranges of thyroid hormones and Serum thyroid stimulating hormone
      (S.TSH) and prevalence of ScHt and thyroid autoimmunity. MATERIALS AND METHODS:
      Two-hundred thirty-seven normal subjects without family history of thyroid
      disease were evaluated for symptoms and laboratory tests for thyroid dysfunction
      and autoimmunity. RESULTS: The thyroid function tests were as follows: EUTHYROID
      GROUP: MEAN VALUES WERE: T3: 1.79 +/- 0.42 ng/mL, T4: 10.23 +/- 2.25 MUg/dL, FT3:
      1.88 +/- 0.19 pg/mL, FT4: 1.12 +/- 0.21 ng/dL, S.TSH: 2.22 +/- 1.06 MUlu/mL.
      10.2% of euthyroid subjects had antimicrosomal antibodies (AMA) +ve (mean titer
      1:918) and 23.6% were anti-thyroid peroxidase autoantibody (anti-TPO) +ve (mean
      titer 15.06 Au/mL). The euthyroid outlier range for S.TSH was 0.3-4.6 MUlu/mL.
      The values were comparable in both the sexes. Those with S.TSH >= 5 MUlu/mL were
      defined to have ScHt. SCHT GROUP: Prevalence of ScHt was 11.3% (M:F ratio 1:3.7).
      74% belonged to 35-54 years age group and prevalence increased with age (post
      menopausal females: prevalence 20%). S.TSH was 9.8 +/- 7.22 MUlu/mL, mean S.AMA
      was 1:5079 (40.7% positivity) and mean S.anti-TPO was 260 Au/mL (47.6%
      positivity). Majority were agoitrous (74%), and stage I goiter was seen in 26% of
      this population. Symptom score of 5-8 was seen in 55% ScHt subjects versus 35%
      normal subjects. CONCLUSION: Mean S.TSH in our population was 2.22 MUlu/mL
      (euthyroid outliers: 0.3-4.6 MUlu/mL); hence, S.TSH above 4.6 MUlu/mL should be
      considered as abnormal. The prevalence of thyroid autoimmunity increases after
      age of 35 years. ScHt presents mainly in agoitrous form and with positive
      antibodies, suggesting autoimmunity as the cause.

PMID- 23869303
TI  - Evaluation of autonomic functions in subclinical hypothyroid and hypothyroid
      patients.
AB  - BACKGROUND: Autonomic dysfunction may contribute to cardiovascular morbidity in
      subclinical hypothyroid patients. It is controversial whether the abnormality
      exists in sympathetic or the parasympathetic function. It is also not known
      whether the severity of autonomic dysfunction is related to the degree of thyroid
      deficiency. DESIGN OF STUDY: Prospective case control. MATERIALS AND METHODS:
      Autonomic functions based on heart rate (HR) and blood pressure (BP) responses to
      various maneuvers were evaluated and scored in twenty two subclinical hypothyroid
      patients, 30-50 years and compared with twenty hypothyroid patients. Biochemical
      estimation of TSH, fT3, fT4, TPO antibody was done. RESULT: Sympathetic function
      abnormalities were seen in 82% subclinical hypothyroid patients and
      85%hypothyroid patients when one test was abnormal. Parasympathetic dysfunction
      was also recorded in eight patients in both groups. When two abnormal tests were
      used as the selection criteria sympathetic function abnormality was observed in
      about 41% subclinical hypothyroid and 65% hypothyroid patients. There were no
      intergroup differences in autonomic functions, score and TPO levels. The TSH
      levels were not related to type or degree of autonomic dysfunction. Systolic BP
      in both groups and diastolic BP in hypothyroid patients were higher with lower
      thyroxine levels but the patients were normotensive. CONCLUSION: Autonomic
      dysfunction of comparable degree was seen in subclinical hypothyroid and
      hypothyroid patients. Sympathetic function abnormality was more common although
      decreased parasympathetic function reactivity was also present. These
      abnormalities were unrelated to TSH levels.

PMID- 23869304
TI  - Assessment of adrenal function in liver diseases.
AB  - BACKGROUND: In recent times, there are reports of adrenal dysfunction in whole
      spectrum of liver disease. Adrenal insufficiency (AI) has been shown to correlate
      with progression of liver disease. Hence this study was conducted to assess
      adrenal function in subjects with acute liver disease (ALD), chronic liver
      disease (CLD) and post liver transplantation (LT). MATERIAL AND METHODS: This
      study included 25 healthy controls, 25 patients of ALD, 20 subjects of CLD with
      Child-Pugh stage A (CLD-1) and 30 with Child-Pugh stage B or C (CLD-2), and 10
      subjects with LT. All subjects were assessed clinically, biochemically and for
      adrenal functions. RESULTS: AI was present in 9 (34.6%) patients with ALD, 20
      (40%) patients with CLD and 4 (40%) in subjects with LT. AI was more common in
      CLD-2 (18 patients - 60%) than CLD-1 (2 patients - 10%). All patients with
      chronic liver disease had significantly lower basal cortisol (8.8+/-4.8, P=0.01),
      stimulated cortisol (18.2+/-6.3, P <0.00001) and incremental cortisol (9.4+/-4.6,
      P <0.00001) as compared to controls. There was increase in percentage of subjects
      with adrenal dysfunction with progression of liver disease as assessed by Child
      Pugh staging. AI was predicted by lower levels of serum protein, serum albumin,
      total cholesterol and HDL cholesterol and higher levels of serum bilirubin and
      INR. Adrenal functions showed recovery following liver transplantation.
      CONCLUSIONS: AI forms important part of spectrum of acute and chronic liver
      disease. Deterioration of synthetic functions of liver disease predicts presence
      of AI, and these patients should be evaluated for adrenal dysfunction
      periodically.

PMID- 23869305
TI  - Dyslipidemic drugs in metabolic syndrome.
AB  - INTRODUCTION: Metabolic syndrome predisposes to diabetes and atherosclerotic
      vascular disease. Statins reduce cardiovascular events, so all metabolic syndrome
      patients should be evaluated for dyslipidemia. Many patients fail to achieve
      lipid goals with statin monotherapy. Co-administration of ezetimibe (EZE) and
      atorvastatin (ATV) may enable more patients to achievelow-density
      lipoproteincholesterol (LDL-C) goal while avoiding risks of high-dose statin
      monotherapy. MATERIALS AND METHODS: The present study compares rosuvastatin (Rsv)
      with a combination of (Atv) and (Eze). Metabolic syndrome patients, 30-70 years
      with LDL-C >=130 mg/dl and a 10-year CHD risk score of 10% were randomized to
      double-blind treatment with (Rsv) 5 mg (n = 67) or (Atv) 10 mg+(Eze) 10 mg (n =
      68) for 12 weeks. RESULTS: LDL-C reduced significantly; (32.3% and 30.3%, P <
      0.001) in (Atv)+(Eze) and (Rsv), respectively, but there was no significant
      difference between two arms. More patients achieved LDL-C goal of <=100 mg/dl
      with (Atv)+(Eze) compared to (Rsv) (65% vs. 58%, P < 0.05). Triglycerides (TG)
      were reduced more with (Atv)+(Eze) compared to (Rsv) (28.1% and 21.4%, P <
      0.001). Greater increase in high-density lipoprotein cholesterol (HDL-C) was
      observed with (Atv)+(Eze). Both treatments were well tolerated. CONCLUSION: This
      study shows that the combination of (Atv)+(Eze) has more efficacy and comparable
      safety to that of (Rsv).

PMID- 23869306
TI  - Cardiac autonomic function in patients with diabetes improves with practice of
      comprehensive yogic breathing program.
AB  - BACKGROUND: The aim of this study was to observe the effect comprehensive yogic
      breathing (Sudarshan Kriya Yoga [SKY] and Pranayam) had on cardiac autonomic
      functions in patients with diabetes. MATERIALS AND METHODS: This is a prospective
      randomized controlled intervention trial. Cardiac autonomic functions were
      assessed in 64 diabetics. Patients were randomized into two groups, one group
      receiving standard therapy for diabetes and the other group receiving standard
      therapy for diabetes and comprehensive yogic breathing program. Standard therapy
      included dietary advice, brisk walking for 45 min daily, and administration of
      oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to
      the participants through a course of 12 h spread over 3 days. It was an
      interactive session in which SKY, a rhythmic cyclical breathing, preceded by
      Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic
      function tests were done before and after 6 months of intervention. RESULTS: In
      the intervention group, after practicing the breathing techniques for 6 months,
      the improvement in sympathetic functions was statistically significant (P 0.04).
      The change in sympathetic functions in the standard therapy group was not
      significant (P 0.75). Parasympathetic functions did not show any significant
      change in either group. When both parasympathetic and sympathetic cardiac
      autonomic functions were considered, there was a trend toward improvement in
      patients following comprehensive yogic breathing program (P 0.06). In the
      standard therapy group, no change in cardiac autonomic functions was noted (P
      0.99). CONCLUSION: Cardiac autonomic functions improved in patients with diabetes
      on standard treatment who followed the comprehensive yogic breathing program
      compared to patients who were on standard therapy alone.

PMID- 23869307
TI  - Prevalence of diabetes mellitus in persons with tuberculosis in a tertiary health
      centre in Lagos, Nigeria.
AB  - CONTEXT: In Nigeria, much has been reported on the unacceptably high disease
      burden of Tuberculosis (TB) and Diabetes Mellitus (DM) but not the possible co
      existence of these diseases. AIM: This study was conducted to document the co
      existence of DM and TB in persons with established TB. SETTINGS AND DESIGN: This
      was a cross-sectional study conducted at a Tertiary hospital's Directly Observed
      Therapy short course clinic in Lagos, South west, Nigeria. MATERIALS AND METHODS:
      Three hundred and fifty one consecutive patients with TB who consented to the
      study participated after a written consent. Ethical approval was given by the
      Ethics committee of the institution. Clinical examination for documentation of
      anthropometric indices and biochemical evaluation for blood glucose levels were
      carried out. RESULTS: The prevalence of DM among the patients with TB was 5.7%.
      About half of the diabetics were diagnosed (2.8%) at the screening. The mean age
      of the participants was 34.9 +/- 13.21 years; the mean duration of symptoms of TB
      was 9.65 +/- 9.49 months. Weight (kg) loss was the most predominant symptom
      occurring in 94% of the patients. There was no significant difference in the
      sputum positivity and duration of cough among patients with TB-DM and those with
      TB alone. CONCLUSION: Diabetes is an important co-morbid feature to be sought in
      patients with TB. This study re-echo the need to raise awareness on screening for
      DM in persons with TB.

PMID- 23869308
TI  - Detection of glycemic abnormalities in adolescents with beta thalassemia using
      continuous glucose monitoring and oral glucose tolerance in adolescents and young
      adults with beta-thalassemia major: Pilot study.
AB  - BACKGROUND: Both insulin deficiency and resistance are reported in patients with
      beta-thalassemia major (BTM). The use of continuous blood glucose monitoring
      (CGM), among the different methods for early detection of glycemic abnormalities,
      has not been studied thoroughly in these adolescents. MATERIALS AND METHODS: To
      assess the oralglucose tolerance (OGT) and 72-h continuous glucose concentration
      by the continuous glucose monitoring system (CGMS) and calculate homeostatic
      model assessment (HOMA), and the quantitative insulin sensitivity check index
      (QUICKI) was conducted in 16 adolescents with BTM who were receiving regular
      blood transfusions every 2-4 weeks and iron-chelation therapy since early
      childhood. RESULTS: SIXTEEN ADOLESCENTS WITH BTM (AGE: 19.75 +/- 3 years) were
      investigated. Using OGTT, (25%) had impaired fasting blood (plasma) glucose
      concentration (BG) (>5.6 mmol/L). 2-h after the glucose load, one of them had BG
      = 16.2 mmol/L (diabetic) and two had impaired glucose tolerance (IGT) (BG > 7.8
      and <11.1 mmol/L). Monitoring the maximum (postprandial) BG using CGMS,4
      adolescents were diagnosed with diabetes (25%) (BG >11.1 mmol/L) and 9 with IGT
      (56%). HOMA and QUICKI revealed levels <2.6 (1.6 +/- 0.8) and >0.33 (0.36 +/-
      0.03), respectively, ruling out significant insulin resistance in these
      adolescents. There was a significant negative correlation between the beta-cell
      function (B%) on one hand and the fasting and the 2-h BG (r=-0.6, and - 0.48, P <
      0.01, respectively) on the other hand. Neither fasting serum insulin nor c
      peptide concentrations were correlated with fasting BG or ferritin levels. The
      average and maximum blood glucose levels during CGM were significantly correlated
      with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01) and with the
      BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P <
      0.001). Ferritin concentrations were correlated with the fasting BG and the 2-h
      blood glucose levels in the OGTT (r = 0.52, and r = 0.43, respectively, P < 0.01)
      as well as with the average BG recorded by CGM (r = 0.75, P < 0.01). CONCLUSION:
      CGM has proven to be superior to OGTT for the diagnosis of glycemic abnormalities
      in adolescents with BTM. Defective beta-cell function rather than insulin
      resistance appeared to be the cause for these abnormalities.

PMID- 23869309
TI  - Protocol of an observational study to evaluate diabetic nephropathy through
      detection of microalbuminuria in Indian patients.
AB  - AIM: To assess the prevalence of persistent microalbuminuria (MAU), its clinical
      correlates by dip stick method, its predictive value for potential kidney disease
      and the utility of this test as objective cue for health care seeking behavior in
      adult Indian patients with type 2 diabetes mellitus. MATERIALS AND METHODS:
      Approximately 400,000 patients shall be enrolled in this multicentric, cross
      sectional study. Patients meeting eligibility criteria shall be screened for MAU
      through urine dipstick test using random daytime single spot urine specimen.
      Result shall be expressed either positive or negative based on the presence or
      absence of albumin in the urine and will be correlated with the corresponding
      random blood glucose. Height, weight, waist circumference and blood pressure
      shall be assessed. There will be three visits with a minimum interval of 28 days
      between two visits, to be completed within 180 days, and at least two of three
      urine tests measured in this period must show elevated albumin levels to diagnose
      MAU. CONCLUSION: Detection of MAU through the dipstick method is postulated to be
      a rapid, reliable test for early detection of diabetic nephropathy, which, in
      turn will help the physician to plan treatment strategy. Further, it will help to
      identify the disease burden on the individual and society, and may serve as an
      objective cue for improved health care seeking behavior, as well as a catalyst
      for health policy change.

PMID- 23869310
TI  - Gonadal dysgenesis and the Mayer-Rokitansky-Kuster-Hauser Syndrome in a girl with
      a 46, XX karyotype: A case report and review of literature.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) is a characteristic syndrome in which the
      Mullerian structures are absent or rudimentary. It is also associated with
      anomalies of the genitourinary and skeletal systems. Its association with gonadal
      dysgenesis is extremely rare and appears to be fortuitous, independent of
      chromosomal anomalies. We report such a case in a 21-year-old girl who presented
      primary amenorrhea and impuberism. The endocrine study revealed
      hypergonadotrophic hypogonadism. The karyotype was normal, 46, XX. No chromosome
      Y was detected at the fluorescence in situ hybridization (FISH) analysis.
      Internal genitalia could not be identified on the pelvic ultrasound and pelvic
      magnetic resonance imaging. Laparoscopy disclosed concomitant ovarian dysgenesis
      and MRKH syndrome. There were no other associated malformations. Hormonal
      substitution therapy with oral conjugated estrogens was begun. The patient has
      been under regular follow-up for the last two years and is doing well. 

PMID- 23869312
TI  - Feminizing adrenal tumors: Our experience about three cases.
AB  - Feminizing adrenal tumors (FATs) are very rare as they account for less than 2%
      of all the adrenal neoplasms. Their prognosis is deemed to be very poor. We aimed
      to present a mono centre (adult and pediatric) experience over a long period of
      time (January 1980 to Jun 2012). During the study period, we observed only three
      cases in men aged 22 (2 cases) and 45 (1 case). They all consulted for a painful
      gynecomastia, decreased libido and impotency. Estradiol was high in two cases at
      presentation, and after a relapsing tumor in the third one. All had big adrenal
      tumors (5.9, 6, and 17 cm), and a mixed secretion composed by high estradiol and
      cortisol. The pathological study argued for malignancy in two cases. But, only
      one had diffuse metastasis and died 4 years after diagnosis; the others diagnosed
      one and three years ago are still alive without any metastasis or relapsing. 

PMID- 23869313
TI  - Hidden diagnosis of multiple endocrine neoplasia-1 unraveled during workup of
      virilization caused by adrenocortical carcinoma.
AB  - Multiple endocrine neoplasia-1 (MEN1) is an autosomal dominant syndrome with
      classic triad of parathyroid hyperplasia, pancreatic neuroendocrine tumors, and
      pituitary adenomas. Other recognized manifestations include carcinoid, cutaneous
      or adrenocortical tumors. It is commonly presented with clinical features related
      to parathyroid, pancreas or pituitary lesions. Here, we have presented a case
      that had virilization and biochemical Cushing's syndrome due to adrenocortical
      carcinoma as presenting feature of MEN1. Cushing's syndrome in MEN1 is an
      extremely rare and usually late manifestation and most cases are due to
      corticotropin-producing pituitary adenomas. Although Cushing's syndrome generally
      develops years after the more typical manifestations of MEN1 appear, it may be
      the primary manifestation of MEN1 syndrome particularly when related to adrenal
      adenoma or carcinoma. 

PMID- 23869314
TI  - Reversible cerebellar ataxia with thyrotoxicosis: An autoimmune brain disease in
      remission due to Graves' disease.
AB  - We hereby report a patient with seizure disorder who was on long term
      carbamazepine, admitted with features of thyrotoxicosis and cerebellar
      dysfunction. Anticonvulsant medications are cerebellar toxins; but in this case,
      reversal of cerebellar dysfunction was noted upon treatment of thyrotoxicosis
      with antithyroid drugs. 

PMID- 23869315
TI  - Thymic hyperplasia in Graves' disease.
AB  - Graves' disease is an autoimmune thyroid condition characterized by the
      production of autoantibodies against the thyrotropin receptor. It is known to be
      associated with autoimmune conditions such as myasthenia gravis, Addison's
      disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare
      autoimmune association of Graves' disease with thymic hyperplasia which regressed
      after treatment with antithyroid drugs. Exact pathophysiology of thymic
      hyperplasia in Graves' is not well understood; it is likely to be the result of
      rather than the cause of Graves' disease. 

PMID- 23869316
TI  - False positive results using calcitonin as a screening method for medullary
      thyroid carcinoma.
AB  - The role of serum calcitonin as part of the evaluation of thyroid nodules has
      been widely discussed in literature. However there still is no consensus of
      measurement of calcitonin in the initial evaluation of a patient with thyroid
      nodule. Problems concerning cost-benefit, lab methods, false positive and low
      prevalence of medullary thyroid carcinoma (MTC) are factors that limit this
      approach. We have illustrated two cases where serum calcitonin was used in the
      evaluation of thyroid nodule and rates proved to be high. A stimulation test was
      performed, using calcium as secretagogue, and calcitonin hyper-stimulation was
      confirmed, but anatomopathologic examination did not evidence medullar neoplasia.
      Anatomopathologic diagnosis detected Hashimoto thyroiditis in one case and
      adenomatous goiter plus an occult papillary thyroid carcinoma in the other one.
      Recommendation for routine use of serum calcitonin in the initial diagnostic
      evaluation of a thyroid nodule, followed by a confirming stimulation test if
      basal serum calcitonin is showed to be high, is the most currently recommended
      approach, but questions concerning cost-benefit and possibility of diagnosis
      error make the validity of this recommendation discussible. 

PMID- 23869317
TI  - Persistence of histoplasma in adrenals 7 years after antifungal therapy.
AB  - Adrenal histoplasmosis is an uncommon cause for adrenal insufficiency. The
      duration of treatment for adrenal histoplasmosis is not clear. Existing treatment
      regimens advocate antifungals given for periods ranging from 6 months to 2 years.
      We report here a rare case who showed persistence of histoplasma in adrenal
      biopsy 7 years after being initially treated with itraconazole for 9 months. This
      calls for a prolonged therapy with regular review of adrenal morphology and
      histology in these patients. 

PMID- 23869318
TI  - Double whammy after pituitary surgery.

PMID- 23869319
TI  - Ethical concerns regarding intersex.

PMID- 23869320
TI  - The diagnosis of Charles Bonnet syndrome in visual field defects.

PMID- 23869321
TI  - Raised liver enzymes in newly diagnosed type 2 diabetes.

PMID- 23869322
TI  - Utility of single photon emission computed tomography/CT hybrid imaging over
      planar I-131 whole body scans in detection of adrenal metastases in
      differentiated thyroid cancer.

PMID- 23869323
TI  - Adult immunization: Is time ripe for its initiation.

PMID- 23869324
TI  - Should depressive patients undergo a regular diabetes screening test?

PMID- 23869325
TI  - A neglected case of headache.

PMID- 23869326
TI  - Successful pregnancy outcome in a case of pheochromocytoma presenting as severe
      pre-eclampsia with normal urinary catecholamine level.

PMID- 23869327
TI  - The effect of continuous epidural electrical stimulation on neuronal
      proliferation in cerebral ischemic rats.
AB  - OBJECTIVE: To investigate the effect of electrical stimulation (ES) on the
      recovery of motor skill and neuronal cell proliferation. METHODS: The male
      Sprague-Dawley rats were implanted with an epidural electrode over the peri
      ischemic area after photothrombotic stroke in the dominant sensorimotor cortex.
      All rats were randomly assigned into the ES group and control group. The
      behavioral test of a single pellet reaching task (SPRT) and neurological
      examinations including the Schabitz's photothrombotic neurological score and the
      Menzies test were conducted for 2 weeks. After 14 days, coronal sections were
      obtained and immunostained for neuronal cell differentiation markers including
      bromodeoxyuridine (BrdU), neuron-specific nuclear protein (NeuN), and
      doublecortin (DCX). RESULTS: On the SPRT, the motor function in paralytic
      forelimbs of the ES group was significantly improved. There were no significant
      differences in neurological examinations and neuronal cell differentiation
      markers except for the significantly increased number of DCX+ cells in the corpus
      callosum of the ES group (p<0.05). But in the ES group, the number of NeuN+ cells
      in the ischemic cortex and the number of NeuN+ cells and DCX+ cells in the
      ischemic striatum tended to increase. In the ES group, NeuN+ cells in the
      ischemic hemisphere and DCX+ cells and BrdU+ cells in the opposite hemisphere
      tended to increase compared to those in the contralateral. CONCLUSION: The
      continuous epidural ES of the ischemic sensorimotor cortex induced a significant
      improvement in the motor function and tended to increase neural cell
      proliferation in the ischemic hemisphere and the neural regeneration in the
      opposite hemisphere.

PMID- 23869329
TI  - The accuracy of the swallowing kinematic analysis at various movement velocities
      of the hyoid and epiglottis.
AB  - OBJECTIVE: To evaluate the accuracy of the swallowing kinematic analysis.
      METHODS: To evaluate the accuracy at various velocities of movement, we developed
      an instrumental model of linear and rotational movement, representing the
      physiologic movement of the hyoid and epiglottis, respectively. A still image of
      8 objects was also used for measuring the length of the objects as a basic
      screening, and 18 movie files of the instrumental model, taken from
      videofluoroscopy with different velocities. The images and movie files were
      digitized and analyzed by an experienced examiner, who was blinded to the study.
      RESULTS: The Pearson correlation coefficients between the measured and
      instrumental reference values were over 0.99 (p<0.001) for all of the analyses.
      Bland-Altman plots showed narrow ranges of the 95% confidence interval of
      agreement between the measured and reference values as follows: 0.14 to 0.94 mm
      for distances in a still image, -0.14 to 1.09 mm/s for linear velocities, and 
      1.02 to 3.81 degree/s for angular velocities. CONCLUSION: Our findings
      demonstrate that the distance and velocity measurements obtained by swallowing
      kinematic analysis are highly valid in a wide range of movement velocity.

PMID- 23869328
TI  - Effect of the presence of brain-derived neurotrophic factor val(66)met
      polymorphism on the recovery in patients with acute subcortical stroke.
AB  - OBJECTIVE: To investigate the effect of brain-derived neurotrophic factor (BDNF)
      Val(66)Met polymorphism on the recovery after subcortical stroke, using the
      modified Rankin Scale (mRS). METHODS: Subcortical stroke patients with copies of
      BDNF Val(66)Met polymorphism (n=7) were compared to their controls (n=7) without
      a copy of BDNF Val(66)Met polymorphism after matching for initial severity,
      location and type of stroke. The mRS scores at 1 and 3 months after discharge
      from the neurorehabilitation unit were compared between the groups. RESULTS: A
      repeated measures ANOVA for mRS revealed significant interaction between time and
      group (F(2, 24) =37.2, p<0.001) and a significant effect of time (F(2, 24)=10.8,
      p<0.001), thereby reflecting significant differences between the Met allele (+)
      group and the Met allele (-) group. There was a significant difference in mRS
      scores at 3 months post-discharge between the two groups (p=0.01) although no
      difference was evident in mRS scores at 1 month post-discharge between the two
      groups. There were significant improvements between mRS scores on admission and
      mRS scores at 1 month post-discharge (p=0.02), and between mRS scores at 1 month
      post-discharge and mRS scores at 3 months post-discharge (p=0.004) in the Met
      allele (-) group. CONCLUSION: BDNF Val(66)Met polymorphism may be associated with
      worse functional outcome in Korean patients with subcortical stroke. Therefore,
      BDNF Val(66)Met polymorphism should be considered as an important prognostic
      factor for recovery and responses to rehabilitation therapies after stroke in
      Korean patients. There is a need for developing different rehabilitation
      strategies for the population with BDNF Val(66)Met polymorphism. Further studies
      assessing different outcomes for various functional domains of stroke recovery
      are needed to clarify the role of BDNF Val(66)Met polymorphism.

PMID- 23869330
TI  - Botulinum Toxin Treatment on Upper Limb Function in School Age Children With
      Bilateral Spastic Cerebral Palsy: One Year Follow-up.
AB  - OBJECTIVE: To prospectively investigate the long-term effects of botulinum toxin
      treatment on the upper limb function and performance of school age children with
      spastic bilateral cerebral palsy, who have limitations in performing activities
      of daily living and school activities, due to spasticity of the upper
      extremities. METHODS: Botulinum type A toxin (BoNT-A) was injected into 24
      spastic upper limbs of 15 children. We used a Modified Ashworth Scale and a
      Modified Tardieu Scale for the evaluation of upper limb spasticity, and Quality
      of Upper Extremity Skills Test (QUEST), Canadian Occupational Performance Measure
      (COPM), and Test of Visual-Motor Skills-Revised (TVMS-R) for the evaluation of
      upper limb function and performance. RESULTS: Upper limb spasticity continuously
      decreased until the end of the one-year follow-up. Upper limb function on QUEST
      and COPM showed the best performance at 3 months and deteriorated slightly, but
      still showed a significantly better performance at 9 and 12 months than at pre
      injection. In more functional nine subjects who could perform TVMS-R, the
      performance enhancement effects remained constant after 12 months, suggesting
      that the reduced spasticity led to the learning effect acquired by the repeated
      use of the affected upper limb. CONCLUSION: For school age children with
      bilateral spastic cerebral palsy whose upper limb functions are important, BoNT-A
      injections seem to be of help in the performance of school activities and
      activities of daily living.

PMID- 23869331
TI  - Characteristics of abdominal obesity in persons with spinal cord injury.
AB  - OBJECTIVE: To investigate the characteristics of community-dwelling spinal cord
      injury (SCI) persons with obesity, including diet, socioeconomic factors, weight
      reduction method, and frequency of body weight and abdominal circumference
      measurements. METHODS: We developed a questionnaire based on 'the Fourth Korea
      National Health and Nutrition Examination Survey, 2009'. A total of 371 community
      dwelling SCI persons were enrolled in this study. Inclusion criteria were SCI
      persons older than 20 years with more than 1 year elapsed since the injury.
      Trained investigators visited SCI persons' home to complete the questionnaire and
      measure abdominal obesity (AO) as defined by the waist circumference. RESULTS:
      Prevalence of AO was 29.2% in SCI persons and 27.4% in the general population
      (GP), showing no significant difference. Education showed correlation with AO in
      both SCI persons and the GP. The injury level, type of injury and income did not
      show any correlation with AO in SCI persons. Only 28.8% and 48.8% of SCI persons
      measured their waist circumference and body weight within the past year,
      respectively. Also, SCI persons with AO thought that their body was less obese
      compared to persons with AO in the GP (p<0.001). The method of weight reduction
      was diet modification in 53.6% of SCI persons with AO, which was higher than
      37.1% of persons with AO in the GP. CONCLUSION: In SCI persons, obesity
      perception as well as socioeconomic factors correlated with AO, but these were
      not relevant factors in the GP. Therefore, development of a specific and
      intensive weight control program for SCI persons is necessary.

PMID- 23869332
TI  - Sequential analysis of postural control resource allocation during a dual task
      test.
AB  - OBJECTIVE: To investigate the postural control factors influencing the automatic
      (reflex-controlled) and attentional (high cortical) factors on dual task.
      METHODS: We used a dual task model to examine the attentional factors affecting
      the control of posture, subjecting test subjects to vibration stimulation, one
      leg standing and verbal or nonverbal task trials. Twenty-three young, healthy
      participants were asked to stand on force plates and their centers of pressure
      were measured during dual task trials. We acquired 15 seconds of data for each
      volunteer during six dual task trials involving varying task combinations.
      RESULTS: We observed significantly different sway patterns between the early and
      late phases of dual task trials, which probably reflect the attentional demands.
      Vibration stimulation perturbed sway more during the early than the late phases;
      with or without vibration stimulation, the addition of secondary tasks decreased
      sway in all phases, and greater decreases in sway were observed in the late
      phases, when subjects were assigned nonverbal tasks. Less sway was observed
      during the nonverbal task in a sequential study. CONCLUSION: The attentional and
      automatic factors were analyzed during a sequential study. By controlling the
      postural control factors, optimal parameters and training methods might be used
      in clinical applications.

PMID- 23869333
TI  - Skin temperature changes in patients with unilateral lumbosacral radiculopathy.
AB  - OBJECTIVE: To clarify the relationship of skin temperature changes to clinical,
      radiologic, and electrophysiological findings in unilateral lumbosacral
      radiculopathy and to delineate the possible temperature-change mechanisms
      involved. METHODS: One hundred and one patients who had clinical symptoms and for
      whom there were physical findings suggestive or indicative of unilateral
      lumbosacral radiculopathy, along with 27 normal controls, were selected for the
      study, and the thermal-pattern results of digital infrared thermographic imaging
      (DITI) performed on the back and lower extremities were analyzed. Local
      temperatures were assessed by comparing the mean temperature differences (DeltaT)
      in 30 regions of interest (ROIs), and abnormal thermal patterns were divided into
      seven regions. To aid the diagnosis of radiculopathy, magnetic resonance imaging
      (MRI) and electrophysiological tests were also carried out. RESULTS: The
      incidence of disc herniation on MRI was 86%; 43% of patients showed
      electrophysiological abnormalities. On DITI, 97% of the patients showed abnormal
      DeltaT in at least one of the 30 ROIs, and 79% showed hypothermia on the involved
      side. Seventy-eight percent of the patients also showed abnormal thermal patterns
      in at least one of the seven regions. Patients who had motor weakness or lateral
      type disc herniation showed some correlations with abnormal DITI findings.
      However, neither pain severity nor other physical or electrophysiological
      findings were related to the DITI findings. CONCLUSION: Skin temperature change
      following lumbosacral radiculopathy was related to some clinical and MRI
      findings, suggesting muscle atrophy. DITI, despite its limitations, might be
      useful as a complementary tool in the diagnosis of unilateral lumbosacral
      radiculopathy.

PMID- 23869334
TI  - Exaggerated response of systolic blood pressure to cycle ergometer.
AB  - OBJECTIVE: The aim of this study is to exam the effects of exercise modes on the
      systolic blood pressure and rate-pressure product during a gradually increasing
      exercise load from low to high intensity. METHODS: Fifteen apparently healthy men
      aged 19 to 23 performed the graded exercise tests on cycle ergometer (CE) and
      treadmill (TM). During the low-to-maximal exercises, oxygen uptake (VO2), heart
      rate (HR), systolic blood pressure (SBP) and rate-pressure product were measured.
      RESULTS: CE had a significantly lower maximum VO2 than TM (CE vs. TM: 48.51+/
      1.30 vs. 55.4+/-1.19 mL/kg/min; p<0.001). However, CE showed a higher maximum SBP
      (SBPmax) at the all-out exercise load than TM (CE vs. TM: 170+/-2.4 vs. 154+/-1.7
      mmHg; p<0.001). During the low-to-maximal intensity increment, the slope of the
      HR with VO2 was the same as VO2 increased in times of the graded exercise test of
      CE and TM (CE vs. TM: 2.542+/-0.100 vs. 2.506+/-0.087; p=0.26). The slope of
      increase on SBP accompanied by VO2 increase was significantly higher in CE than
      in TM (CE vs. TM: 1.669+/-0.117 vs. 1.179+/-0.063; p<0.001). CONCLUSION: The SBP
      response is stronger in CE than in TM during the graded exercise test. Therefore,
      there is a possibility that CE could induce a greater burden on workloads to
      cardiovascular system in humans than TM.

PMID- 23869335
TI  - Factors related to standing balance in patients with knee osteoarthritis.
AB  - OBJECTIVE: To assess factors related to standing balance in patients with knee
      osteoarthritis (OA). METHODS: In total, 37 female patients with painful knee OA
      were included. Pain, knee alignment, and Kellgren and Lawrence grade were
      evaluated accordingly. Static standing balance was measured with a force-platform
      system under two different conditions: static standing with eyes open (EO) and
      eyes closed (EC) for 30 seconds. The mean speed (mm/s) of movement of the center
      of pressure in the anteroposterior (AP) and mediolateral directions and the mean
      velocity moment (mm(2)/s) were analyzed for assessment of static balance.
      RESULTS: In the univariate regression analysis, age and knee alignment showed
      statistically significant relationships with the mean speed in the AP directions
      with EO. In the multiple linear regression model, age and knee alignment were
      positively associated and disease severity was negatively associated with mean
      speed in the AP directions with EO. However, the variables for EC static
      measurements were not significantly correlated with age, pain, knee alignment, or
      radiographic severity (p>0.05). CONCLUSION: These findings show that the worse
      balance was associated with advanced age, less varus knee malalignment, and mild
      radiographic changes. Pain was not associated with standing balance.

PMID- 23869336
TI  - Dose-related effect of extracorporeal shock wave therapy for plantar fasciitis.
AB  - OBJECTIVE: To examine the dose-related effect of extracorporeal shock wave
      therapy (ESWT) for plantar fasciitis. METHODS: Sixty patients with plantar
      fasciitis despite conservative treatment were enrolled. The patients were divided
      into a low-energy group (group L: n=30, 1,000 shocks/session, energy flux density
      [EFD] per shock 0.08 mJ/mm(2)) and a medium-energy group (group M: n=30, 1,000
      shocks/session, EFD 0.16 mJ/mm(2)). The main outcome measures were visual
      analogue scale (VAS), Roles and Maudsley (RM) score, and thickness of plantar
      fascia (PF). To compare the effects between each group, follow-up was carried out
      1 week after 3 and 6 sessions, and 1 and 3 months after ESWT. RESULTS:
      Significant VAS and RM score improvement, and PF thickness reduction were
      observed in both groups (p<0.01). After 3 sessions of ESWT, group M showed
      significant improvement in the VAS and RM score than group L, whereas after 3
      additional sessions applied in group L, the main outcomes were no longer
      significantly different in both groups (p>0.05). CONCLUSION: Therapeutic effect
      might disclose a dose-related relationship; therefore, EFD and the times of the
      session are considerable factors when treating with ESWT.

PMID- 23869338
TI  - Clinical effectiveness of complex decongestive physiotherapy for malignant
      lymphedema: a pilot study.
AB  - OBJECTIVE: To evaluate the effect of complex decongestive physiotherapy (CDPT) on
      malignant lymphedema patients. METHODS: Patients (n=22) with malignant lymphedema
      of the upper or the lower limb were assigned to this study. CDPT without manual
      lymphatic drainage (MLD) was used five times per week for two weeks. The main
      outcome measurements included measurement of the circumference of the limb
      (proximal, distal, and total) to assess volume changes. We also employed the
      visual analog scale (VAS) to evaluate pain, and the short form-36 version 2
      questionnaire (SF-36) to assess quality of life (QOL). All items were assessed
      pre and post-treatment for each patient. RESULTS: There was a statistically
      significant difference in the volume change of the upper limbs (3.7%, p=0.001)
      and the lower limbs (10.9%, p=0.001). A 1.5 point reduction on the ten-point VAS
      was noted after CDPT. The scores on the physical and the mental components of the
      SF-36 showed statistical improvement after treatment (p=0.006, p=0.001,
      respectively). CONCLUSION: These results suggest that all components of the CDPT
      program except MLD are helpful in treating malignant lymphedema in terms of pain
      reduction and reduction of the volume of the affected upper or lower limb. This
      treatment regimen also has positive effects on QOL.

PMID- 23869337
TI  - The relationship between muscle fatigue and balance in the elderly.
AB  - OBJECTIVE: To investigate the effect of gastrocnemius muscle fatigue on postural
      control ability in elderly people. METHODS: Twenty-four healthy elderly people
      participated in this study. The postural control ability of single leg standing
      was evaluated with Health Improvement & Management System (HIMS) posturography
      before and after fatiguing exercises. After evaluating initial postural control
      ability, the maximal voluntary contraction (MVC) of ankle plantarflexion was
      assessed using a surface electromyogram from the medial belly of the
      gastrocnemius muscle. After a 5-minute resting period, subjects began submaximal
      isometric ankle plantarflexion (40% MVC) until 40% of MVC was dropped below 95%
      for 5 seconds, or subject couldn't continue working out due to muscle fatigue.
      And postural control ability was assessed after fatiguing exercise. The mean
      deviation of center of pressure (COP), length of COP movement, occupied area of
      COP were measured, and analyzed by paired t-test. RESULTS: Mediolateral
      deviation, length of COP movement, and area of COP occupied were increased after
      fatiguing exercise of the gastrocnemius muscle. Anteroposterior deviation and
      length of COP movement were also increased, but had low statistical significance.
      CONCLUSION: These findings suggest that the gastrocnemius muscle fatigue affects
      mediolateral stability and accuracy during single leg standing in elderly people.
      Therefore muscle endurance training is necessary to prevent falls in elderly
      people.

PMID- 23869339
TI  - Validity of motor impairment scale in long-term care insurance system of Korea.
AB  - OBJECTIVE: To validate the Motor Impairment Scale (MIS) of the Korean long-term
      care insurance (LTCI) system by comparing with the service time offered for
      aiding activities of daily living (ADL) and the ADL score. METHODS: A total of
      407 elderly subjects without dementia who had used LTCI services were included in
      this study. Spearman correlations and multivariate linear regression models were
      employed to determine the relationship of the upper and lower limb MIS (U-MIS and
      L-MIS, respectively) to the service time and ADL. Stratified analyses for the
      facility group (n=121) and the domiciliary group (n=286) were performed. RESULTS:
      There were significant differences in characteristics between facility group and
      domiciliary group. The MIS was significantly correlated with service time in
      facility group (Spearman p=0.41 for U-MIS, Spearman p=0.40 for L-MIS). After
      adjusting for age, sex, and cognition score, U-MIS was an independent predictor
      for service time in facility group (p=0.04). In domiciliary group, no significant
      correlation was found between the MIS and service time. The MIS correlated with
      all of the ADL items and total ADL score in both groups. After adjusting for
      other factors including age, sex, and cognitive score, U-MIS and L-MIS were
      independent variables for explaining the total ADL score in both groups.
      CONCLUSION: The validity of the MIS as an evaluation tool in the physically
      disabled elderly is higher in facility group than in domiciliary group. As an
      easy, objective, and simple method, MIS can be a useful tool in the LTCI system
      of Korea.

PMID- 23869341
TI  - A case of the cauda equina syndrome associated with the intrathecal chemotherapy
      in a patient with primary central nervous system lymphoma.
AB  - The intrathecal chemotherapy with methotrexate and cytarabine arabinoside is used
      for the treatment and prophylaxis of the primary central nervous system lymphoma.
      The therapy may induce neurotoxicity including the cauda equina syndrome. We
      report a case of a 58-year-old man with the diffuse large B-cell lymphoma, who
      developed the cauda equina syndrome after the administration of intrathecal
      methotrexate and cytarabine arabinoside, as diagnosed by the electrodiagnostic,
      urodynamic, and radiologic approaches. 

PMID- 23869340
TI  - Analysis of publication status of abstracts presented at the annual meeting of
      the korean academy of rehabilitation medicine.
AB  - OBJECTIVE: To analyze publication rate, time to publication and the
      characteristics of the abstracts presented at the annual Korean Academy of
      Rehabilitation Medicine (KARM) meetings. METHODS: A total of 1,027 abstracts
      presented at the 2008 and 2009 annual KARM meetings were enrolled in the database
      and searched for their subsequent citation in PubMed, KoreaMed, and Google
      Scholar. RESULTS: The data analysis revealed that 317 (30.87%) abstracts, were
      published as full-length journal articles and publication rates by subject were
      not significantly different. The mean time to publication was 17.17+/-10.48
      months, and the journals written in English (20.39+/-10.20) required a longer
      duration than those written in Korean (11.94+/-8.44) with statistical
      significance (p<0.001). There was no statistical difference (p=0.284) in the
      duration between domestic (17.61+/-10.37) and foreign (16.48+/-10.51) of the 220
      domestic journal articles, 190 (86.76%) were published in the Annals of
      Rehabilitation Medicine and the 97 articles published in foreign journals were
      scattered over 60 different journals. CONCLUSION: The publication rate of
      abstracts presented at the 2008 and 2009 annual KARM meetings was 30.87% and the
      mean time to publication was 17.17+/-10.48 months.

PMID- 23869342
TI  - The effect of balloon dilation at the vallecular using videofluoroscopic
      swallowing study on patient who has a Dysphagia.
AB  - Authors have previously experienced the effect of balloon dilation at the
      vallecular by utilizing the video-fluoroscopic swallowing study (VFSS) and the
      urethral catheter to physically stretch and spread in the direction of the
      posterior inferior towards the patients who have claimed for dysphagia symptoms
      due to epiglottic dysfunction. A 72-year-old male patient has been diagnosed with
      rectal cancer and have been treated with an ileocolostomy after the intubation.
      After the removal of tracheal intubation, the patient complained of dysphagia.
      Foods and drinks could not be transmigrated into the esophagus due to the
      inability of the epiglottis to bend backward in the direction of posterior
      inferior on VFSS. The epiglottis was physically stretched and spread in the
      direction of posterior inferior by utilizing the balloon attached to a urethral
      catheter. After stretching and spreading the epiglottis in the direction of
      posterior inferior, the bolus remaining in the epiglottic vallecula was
      decreased. For a patient who is experiencing dysphagia due to an epiglottis
      disorder, it seems that an epiglottis balloon dilation supported by VFSS and a
      urethral catheter may be appropriate for the treatment of dysphagia symptoms. 

PMID- 23869343
TI  - A case report of long-term bisphosphonate therapy and atypical stress fracture of
      bilateral femur.
AB  - Bisphosphonates are potent inhibitors of bone resorption and considered as a gold
      standard and are generally recommended as first-line therapy in patients with
      osteoporosis. Though bisphosphonates are shown to significantly reduce the risk
      of vertebral, non-vertebral and hip fractures, recent reports suggest a possible
      correlation between long-term bisphosphonate therapy and the occurrence of
      insufficiency fractures owing to prolonged bone turnover suppression. We report a
      patient with non-traumatic stress fractures of bilateral femoral shafts related
      to long-term bisphosphonate therapy indicating the need for a critical evaluation
      of patients with long-term bisphosphonate therapy. 

PMID- 23869344
TI  - Diagnosis of zygomaticus muscle paralysis using needle electromyography with
      ultrasonography.
AB  - A 22-year-old woman visited our clinic with a history of radiofrequency
      volumetric reduction for bilateral masseter muscles at a local medical clinic.
      Six days after the radiofrequency procedure, she noticed a facial asymmetry
      during smiling. Physical examination revealed immobility of the mouth drawing
      upward and laterally on the left. Routine nerve conduction studies and needle
      electromyography (EMG) in facial muscles did not suggest electrodiagnostic
      abnormalities. We assumed that the cause of facial asymmetry could be due to an
      injury of zygomaticus muscles, however, since defining the muscles through
      surface anatomy was difficult and it was not possible to identify the muscles
      with conventional electromyographic methods. Sono-guided needle EMG for
      zygomaticus muscle revealed spontaneous activities at rest and small amplitude
      motor unit potentials with reduced recruitment patterns on volition. Sono-guided
      needle EMG may be an optimal approach in focal facial nerve branch injury for the
      specific localization of the injury lesion. 

PMID- 23869345
TI  - Traumatic atlanto-occipital dislocation presenting with Dysphagia as the chief
      complaint: a case report.
AB  - We report a patient with traumatic atlanto-occipital dislocation who presented
      with dysphagia as the chief complaint. A 59-year-old man complained of swallowing
      difficulty for 2 months after trauma to the neck. On physical examination, there
      was atrophy of the right sternocleidomastoid and upper trapezius muscles, and the
      tongue was deviated to the right. In a videofluoroscopic swallowing study,
      penetration and aspiration were not seen, food residue remained in the right
      vallecula and pyriform sinus, and there was decreased motion of the soft palate,
      pharynx and larynx. Electromyography confirmed a right spinal accessory nerve
      lesion. Magnetic resonance imaging confirmed atlanto-occipital dislocation.
      Dysphagia in atlanto-occipital dislocation is induced by medullary compression
      and lower cranial nerve injury. Therefore, in survivors who are diagnosed with
      atlanto-occipital dislocation, any neurological symptoms should be carefully
      evaluated. 

PMID- 23869346
TI  - The selection of the appropriate computer interface device for patients with high
      cervical cord injury.
AB  - In order to determine the most suitable computer interfaces for patients with
      high cervical cord injury, we report three cases of applications of special input
      devices. The first was a 49-year-old patient with neurological level of injury
      (NLI) C4, American Spinal Injury Association Impairment Scale (ASIA)-A. He could
      move the cursor by using a webcam-based Camera Mouse. Moreover, clicking the
      mouse could only be performed by pronation of the forearm on the modified Micro
      Light Switch. The second case was a 41-year-old patient with NLI C3, ASIA-A. The
      SmartNav 4AT which responds according to head movements could provide stable
      performance in clicking and dragging. The third was a 13-year-old patient with
      NLI C1, ASIA-B. The IntegraMouse enabling clicking and dragging with fine
      movements of the lips. Selecting the appropriate interface device for patients
      with high cervical cord injury could be considered an important part of
      rehabilitation. We expect the standard proposed in this study will be helpful. 

PMID- 23869347
TI  - Vernet syndrome by varicella-zoster virus.
AB  - Vernet syndrome involves the IX, X, and XI cranial nerves and is most often
      attributable to malignancy, aneurysm or skull base fracture. Although there have
      been several reports on Vernet's syndrome caused by fracture and inflammation,
      cases related to varicella-zoster virus are rare and have not yet been reported
      in South Korea. A 32-year-old man, who complained of left ear pain, hoarse voice
      and swallowing difficulty for 5 days, presented at the emergency room. He showed
      vesicular skin lesions on the left auricle. On neurologic examination, his uvula
      was deviated to the right side, and weakness was detected in his left shoulder.
      Left vocal cord palsy was noted on laryngoscopy. Antibody levels to varicella
      zoster virus were elevated in the serum. Electrodiagnostic studies showed
      findings compatible with left spinal accessory neuropathy. Based on these
      findings, he was diagnosed with Vernet syndrome, involving left cranial nerves,
      attributable to varicella-zoster virus. 

PMID- 23869348
TI  - Flaccid leg paralysis caused by a thoracic epidural catheterization: a case
      report.
AB  - We report a case of a 44-year-old patient with paralysis of the left leg who had
      a thoracic epidural catheterization after general anesthesia for abdominal
      surgery. Sensory losses below T10 and motor weakness of the left leg occurred
      after the surgery. Magnetic resonance image study demonstrated a well-defined
      intramedullary linear high signal intensity lesion on T2-weighted image and low
      signal intensity on T1-weighted image in the spinal cord between T9 and L1
      vertebral level, and enhancements of the spinal cord below T8 vertebra and in the
      cauda equina. Electrodiagnostic examination revealed lumbosacral
      polyradiculopathy affecting nerve roots below L4 level on left side. We suggest
      that the intrinsic spinal cord lesion and nerve root lesion can be caused by an
      epidural catheterization with subsequent local anesthetic injection. 

PMID- 23869350
TI  - Lclet 4 enhances pro-apoptotic and anti-invasive effects of mitoxantrone on human
      prostate cancer cells - in vitro study.
AB  - Triterpene saponosides are widely distributed plant secondary metabolites
      characterized by relatively low systemic cytotoxicity and a range of biological
      activities. These include anti-inflammatory, antimicrobial, vasoprotective and
      antitumor properties. In particular, the ability of saponins to enhance the
      cytotoxicity of chemotherapeutic drugs opened perspectives for their application
      in combined cancer chemotherapy. Here, we used human prostate cancer DU-145 cells
      as an in vitro model to elucidate the synergy of the interactions between
      biological activities of an oleanane type 13beta,28-epoxy triterpene saponoside
      (Lclet 4) and mitoxantrone, which is a cytostatic drug commonly used in prostate
      cancer therapy. No cytotoxic or pro-apoptotic effect of Lclet 4 and mitoxantrone
      administered at the concentrations between 0.05 and 0.1 ug/ml could be seen. In
      contrast, cocktails of these agents exerted synergistic pro-apoptotic effects,
      accompanied by the activation of the caspase 3/7 system. This effect was
      paralleled by attenuating effects of Lclet 4/mitoxantrone cocktails on the
      invasive potential, metalloproteinase expression and motility of DU-145 cells.
      Multifaceted and additive effects of Lclet 4 and mitoxantrone on basic cellular
      traits crucial for prostate cancer progression indicate that the combined
      application of both agents at systemically neutral concentrations may provide the
      basis for new promising strategies of prostate cancer chemotherapy.

PMID- 23869351
TI  - The changing faces of laboratory technology.

PMID- 23869352
TI  - Plasma of argon accelerates murine fibroblast adhesion in early stages of
      titanium disk colonization.
AB  - PURPOSE: This study was conducted to analyze how a cleaning treatment using
      plasma of argon would affect fibroblast growth on titanium disks at different
      time points to determine whether this treatment could enhance soft tissue healing
      around titanium dental implant abutments. MATERIALS AND METHODS: Sixty sterile
      disks made of machined grade 5 titanium were divided into two groups; 30 disks
      were left untreated (control) and 30 were cleaned using plasma of argon (test).
      To simulate clinical conditions during soft tissue healing around titanium
      abutments, both groups were immersed in a culture of murine fibroblasts (L929)
      for 2, 8, or 48 hours. After preparation, they were stained using 4',6-diamidino
      2-phenylindole dihydrochloride (DAPI) to label the cellular nuclei and
      fluorescent phalloidin to label the cellular bodies. The nuclei were counted, and
      cellular bodies were analyzed with fluorescent microscopy and imaging analysis
      software. Analysis was performed at the three different time points. RESULTS:
      Fibroblast adhesion for the test group was statistically significantly greater
      versus the control group at 2 and 8 hours but not at 48 hours. At 2 and 8 hours,
      the cellular bodies in the test group appeared flatter and more spread out,
      revealing more advanced cellular adhesion, compared to the cells observed in the
      control group. At 48 hours, the test and control specimens were nearly
      indistinguishable. CONCLUSION: The removal of organic and inorganic contaminants
      from the surfaces of titanium disks using plasma of argon accelerated fibroblast
      adhesion in the early stages of colonization (2 to 8 hours). This effect
      disappeared after 48 hours as a result of saturation. Clinically, abutment
      cleaning using plasma of argon might positively affect soft tissue healing in
      early stages.

PMID- 23869353
TI  - Effects of anodized titanium with Arg-Gly-Asp (RGD) peptide immobilized via
      chemical grafting or physical adsorption on bone cell adhesion and
      differentiation.
AB  - PURPOSE: This study examined the effects of the immobilization of Arg-Gly-Asp
      (RGD) peptide (CAAALLLKERGDSK) on anodized titanium (Ti) via chemical grafting or
      physical adsorption methods on cell adhesion and osteoblast differentiation.
      MATERIALS AND METHODS: The RGD peptide was immobilized on the anodized Ti surface
      by means of physical adsorption or chemical grafting. The chemical composition of
      each RGD-immobilized Ti substrate was examined by x-ray photoelectron
      spectroscopy. The level of cell proliferation was investigated via tetrazolium
      (XTT) assay. Alkaline phosphatase activity and calcium deposition were evaluated
      by alizarin red S staining, and mRNA expression of the differentiated osteoblast
      marker genes was analyzed by reverse-transcriptase polymerase chain reaction.
      RESULTS: Cell adhesion was enhanced on the RGD-immobilized Ti substrates compared
      to the anodized Ti surfaces. In addition, significantly increased cell spreading
      and proliferation were observed with the cells grown on the RGD-immobilized Ti (P
      < .05). Furthermore, the osteoblasts on the RGD-immobilized Ti showed significant
      increases in the integrin ?1 and type I collagen levels and small increases in
      osteonectin and osteocalcin levels (P < .05). Interestingly, the chemical
      grafting method resulted in significantly greater effects on adhesion and
      differentiation than the physical adsorption method (P < .05). CONCLUSION: RGD
      immobilized Ti substrates might be effective in improving the osseointegration of
      dental implants. In particular, the chemical grafting method of RGD
      immobilization is more favorable and is expected to provide positive outcomes
      with future animal and clinical studies.

PMID- 23869354
TI  - Preparation of thermoplastic poly(L-lactic acid) membranes for guided bone
      regeneration.
AB  - PURPOSE: The objective of this study was to evaluate the feasibility of
      application of thermoplastic poly-L lactic acid (PLLA) membranes for guided bone
      regeneration in rabbit parietal bone. MATERIALS AND METHODS: PLLA membranes with
      a molecular weight of 100,000 (PLLA-100,000) and a molecular weight of 380,000
      (PLLA-380,000) were dissolved in chloroform to prepare concentrations of 8% by
      weight and 4% by weight, respectively. The compression strength, temperature, and
      time to prepare each formulation were measured. Moreover, the pH was noted and
      cytotoxicity of the membrane was determined by monotetrazolium assay. In vivo
      experiments were performed to measure the volume of newly formed bone tissue in
      hematoxylin and eosin-stained tissue sections 4 and 12 weeks after implantation.
      RESULTS: The membrane prepared from PLLA-380,000 showed excellent
      thermoplasticity at 75 degrees C to 80 degrees C and the compressive strength was
      equal to that of titanium mesh, in contrast to that of PLLA-100,000 and
      poly(lactic acid-co-glycolic acid). There was a significant change in the pH of
      an aqueous solution in which the PLLA-380,000 membrane was placed, but there was
      no cytotoxic activity. The membrane made of PLLA-380,000 induced new bone
      formation in a dome shape without any membrane deformation. CONCLUSION:
      Thermoplastic PLLA membrane shows promise for guided bone regeneration in
      vertical bone augmentation.

PMID- 23869355
TI  - Antimicrobial peptide coating of dental implants: biocompatibility assessment of
      recombinant human beta defensin-2 for human cells.
AB  - PURPOSE: Artificial materials such as dental implants are at risk of bacterial
      contamination in the oral cavity. Human beta defensins (HBDs), small cationic
      antimicrobial peptides that exert a broad-spectrum antibacterial function at
      epithelial surfaces and within some mesenchymal tissues, could probably help to
      reduce such contamination. HBDs also have protective immunomodulatory effects and
      have been reported to promote bone remodeling. The aim of this study, therefore,
      was to investigate the influence of recombinant HBD-2 on the proliferation and
      survival of cells in culture. MATERIALS AND METHODS: Human mesenchymal stem cells
      (hMSCs), human osteoblasts, human keratinocytes (control), and the HeLa cancer
      cell line (control) were incubated with recombinant HBD-2 (1, 5, 10, or 20
      MUg/mL). Cell proliferation and cytotoxicity were evaluated via a water-soluble
      tetrazolium salt (WST-1) and lactate dehydrogenase assays, respectively. RESULTS:
      HBD-2 was not toxic in any tested concentration to hMSCs, osteoblasts,
      keratinocytes, or HeLa cells. Furthermore, proliferation of hMSCs and osteoblasts
      increased after treatment with HBD-2 at all tested concentrations, and
      keratinocyte proliferation increased when treated at 20 MUg/mL. In contrast, HeLa
      cancer cells were not affected by HBD-2 as tested. CONCLUSIONS: HBD-2 is not only
      biocompatible but also promotes proliferation of hMSCs, osteoblasts, and
      keratinocytes in culture. Further investigation of HBD-2 functional surface
      coating of artificial materials is recommended.

PMID- 23869356
TI  - Effects of implant system, impression technique, and impression material on
      accuracy of the working cast.
AB  - PURPOSE: This in vitro study aimed to identify the effects of the implant system,
      impression technique, and impression material on the transfer accuracy of implant
      impressions. The null hypothesis tested was that, in vitro and within the
      parameters of the experiment, the spatial relationship of a working cast to the
      placement of implants is not related to (1) the implant system, (2) the
      impression technique, or (3) the impression material. MATERIALS AND METHODS: A
      steel maxilla was used as a reference model. Six implants of two different
      implant systems (Standard Plus, Straumann; Semados, Bego) were fixed in the
      reference model. The target variables were: three-dimensional (3D) shift in all
      directions, implant axis direction, and rotation. The target variables were
      assessed using a 3D coordinate measuring machine, and the respective deviations
      of the plaster models from the nominal values of the reference model were
      calculated. Two different impression techniques (reposition/pickup) and four
      impression materials (Aquasil Ultra, Flexitime, Impregum Penta, P2 Magnum 360)
      were investigated. In all, 80 implant impressions for each implant system were
      taken. Statistical analysis was performed using multivariate analysis of
      variance. RESULTS: The implant system significantly influenced the transfer
      accuracy for most spatial dimensions, including the overall 3D shift and implant
      axis direction. There was no significant difference between the two implant
      systems with regard to rotation. Multivariate analysis of variance showed a
      significant effect on transfer accuracy only for the implant system. CONCLUSIONS:
      Within the limits of the present study, it can be concluded that the transfer
      accuracy of the intraoral implant position on the working cast is far more
      dependent on the implant system than on the selection of a specific impression
      technique or material.

PMID- 23869357
TI  - A comparison of precision of fit, rotational freedom, and torque loss with copy
      milled zirconia and prefabricated titanium abutments.
AB  - PURPOSE: The present study sought to compare copy-milled zirconia abutments with
      standard prefabricated titanium abutments in terms of horizontal and vertical
      misfit, rotational freedom, and torque loss. MATERIALS AND METHODS: Twenty
      regular-platform implants (Branemark, Nobel Biocare) with a standard external
      hexagon implant-abutment interface were divided into two groups. In one group,
      prefabricated titanium abutments (Easy Abutment, Nobel Biocare) were used; in the
      other group, custom-made zirconia abutments were fabricated using the Zirkonzahn
      milling system. Measurements of geometry, rotational freedom, and marginal
      discrepancy were performed using a video measuring machine. To measure torque
      loss, each abutment was torqued to 32 Ncm and then loosened with a digital torque
      wrench. The torque loss values were reported as a percentage of the applied
      torque. RESULTS: Rotational freedom and horizontal misfit were significantly
      higher with the customized abutments. There were no statistically significant
      differences in vertical misfit or in mean percentage of torque loss between the
      two groups. CONCLUSIONS: Within the limitations of this study, it could be
      concluded that copy-milled zirconia abutments do not fit as accurately as
      prefabricated titanium abutments. However, the less precise fit of customized
      zirconia abutments does not seem to affect their ability to maintain the applied
      torque.

PMID- 23869358
TI  - Effect of aging and porcelain sintering on rotational freedom of internal-hex one
      piece zirconia abutments.
AB  - PURPOSE: The purpose of this study was to assess the variation of rotational
      freedom at the implant interface of yttria-stabilized tetragonal zirconia
      polycrystal (Y-TZP) ceramic abutments with internal-hexagon connections before
      and after artificial aging and after porcelain sintering. MATERIALS AND METHODS:
      Thirty Y-TZP ceramic abutments with internal-hex connections were used in this
      study. Three groups of 10 abutments each were created. Group C was made up of
      abutments in the as-received condition, group A abutments went through 1 hour of
      autoclaving at 134 degrees C to simulate the effect of 3 to 4 years of aging in
      vivo, and group P abutments went through porcelain sintering procedures.
      Measurements of rotational freedom were compared between groups. The quantitative
      differences between groups were assessed using multivariate analysis of variance.
      Statistical testing was carried out at the 5% significance level. RESULTS: A mean
      rotational freedom of 115.34 +/- 1.42 minutes was found for group C abutments;
      the values for group A and group P abutments were 115.35 +/- 1.73 minutes and
      115.37 +/- 1.54 minutes, respectively. None of these differences were
      statistically significant between the three groups. CONCLUSION: Misfit of the Y
      TZP ceramic abutment on the internal-hex connection of implants may be implicated
      in screw joint loosening. The results of this report suggested that, if all
      laboratory steps are followed carefully, changes will not occur at the implant/Y
      TZP ceramic abutment interface. Maintenance of the original features of the
      abutment may reduce the risk of screw loosening.

PMID- 23869359
TI  - Novel cell-free regeneration of bone using stem cell-derived growth factors.
AB  - PURPOSE: Tissue engineering and regenerative medicine may now be used for the
      treatment of maxillofacial defects, but the related procedures have several
      limitations, including high capital investment, expensive cell culture
      techniques, and complicated safety and quality management issues. Stem cells
      secrete many cytokines that can affect cell mobilization and differentiation that
      accumulate in conditioned media. This study investigated the effects of stem cell
      conditioned media from human bone marrow-derived mesenchymal stem cells (MSCs) on
      bone regeneration and its ability to induce endogeneous stem cell mobilization
      and bone regeneration. MATERIALS AND METHODS: Human MSCs that were 70% to 80%
      confluent were refed with serum-free Dulbecco's modified Eagle medium, and the
      cell-cultured conditioned media were collected after 48 hours of incubation. The
      collected media were defined as cultured conditioned media from MSCs (MSC-CM).
      Rat bone-marrow-derived stem cells (rMSCs) were cultured with MSC-CM for 48
      hours; then, cell mobilization and the expression of osteogenic-related genes
      were investigated. The presence of cytokines in MSC-CM was determined by enzyme
      linked immunosorbent assay. Collagen sponge was then soaked in MSC-CM and grafted
      into rat calvarial bone defects. At 2 or 4 weeks after implantation of graft
      materials, implanted sections were evaluated by microcomputed tomography and
      histologic analysis. RESULTS: MSC-CM enhanced the migration, proliferation, and
      expression of osteogenic marker genes, such as alkaline phosphatase, osteocalcin,
      and Runx2, of rMSCs in vitro. Cytokines such as insulinlike growth factor-1,
      vascular endothelial growth factor, transforming growth factor-beta1, and
      hepatocyte growth factor were present in the MSC-CM. MSC-CM significantly
      increased the migration and expression of osteogenic-related genes of rMSCs.
      Early bone regeneration in rat calvaria was also observed. CONCLUSION: These
      results suggest that MSC-CM may have potential for novel cell-free regeneration
      of bone.

PMID- 23869360
TI  - Survey of currently selected dental implants and restorations by prosthodontists.
AB  - PURPOSE: The purpose of this study was to survey the prosthodontists of the
      American College of Prosthodontists (ACP) and the American Academy of
      Maxillofacial Prosthetics (AAMP) to identify the most commonly used implant both
      during their training and currently in practice, and to evaluate overall
      restorative preference. Participants were asked to rank criteria that make an
      implant company desirable and important features when selecting an implant.
      MATERIALS AND METHODS: An electronic survey was emailed to 1,739 members of the
      ACP and AAMP. RESULTS: The majority of respondents (79%) were trained using Nobel
      Biocare brand implants, which was also the brand most often selected by
      participants for use in all regions of the oral cavity (34% to 39%, location
      dependent). Abutment preferences varied by area: incisors and canines (29%) and
      highly esthetic areas (53%) were more likely to be restored with custom milled
      zirconia abutments, while prefabricated titanium abutments were preferred for
      premolars and molar areas. Conventional loading was most often applied, ranging
      from 95% in medically compromised patients to 55% in esthetic areas. The majority
      of participants (86%) used Locator attachments for complete overdenture
      restorations. Also, respondents selected an implant company based on features and
      literature support versus cost and customer service. The implant features deemed
      most important were the design of the internal connection and ease of finding
      replacement parts; thread design and variety of abutments were deemed least
      important. Respondents reported that while implant planning software was used,
      they rarely/never order the concurrent surgical guide. CONCLUSION: Within the
      study's limitations, the majority of prosthodontists select implants based on
      training, features, and literature support.

PMID- 23869361
TI  - Physicochemical, pharmacologic, and in vitro cellular effects of loading collagen
      membranes with zoledronic acid.
AB  - PURPOSE: There is a need for improved methods of reducing peri-implant bone loss.
      This study evaluated the structural, drug loading, drug release, and in vitro
      characteristics of collagen membranes impregnated with zoledronic acid (ZA).
      MATERIALS AND METHODS: Two commercially available collagen barrier membranes (Bio
      Gide and BME-10X) were loaded with ZA. The physicochemical and pharmacologic
      properties of the membranes were characterized with scanning electron microscopy,
      energy dispersive spectroscopy, Fourier transform infrared spectroscopy, and high
      performance liquid chromatography. The ZA-loaded membrane's inhibition of
      osteoclasts and promotion of osteoblast growth was evaluated in vitro at ZA
      concentrations of 0, 10(-4), 10(-3), and 10(-2) mol/L. RESULTS: The disappearance
      of micropores between Bio-Gide collagen fibers and the formation of crystalloids
      on the surface of BME-10X membranes following ZA loading was evident under the
      microscope. Phosphorus was detected on the membranes, and amide shifts were
      observed. Greater amounts of ZA loading and slower ZA release were evident for
      Bio-Gide membranes. Osteoclast numbers were reduced with ZA, and a corresponding
      decrease in bone resorption was evident at higher ZA concentrations (P < .05).
      After 7 days, at a ZA concentration of 10(-3) mol/L, Bio-Gide membranes had an
      increased osteoblast proliferation index, while both types of membranes displayed
      increased alkaline phosphatase expression. CONCLUSION: Collagen membranes loaded
      with ZA provided delayed drug release. This study may offer a novel therapeutic
      strategy for minimizing peri-implant bone resorption.

PMID- 23869362
TI  - Diamondlike carbon coating as a galvanic corrosion barrier between dental implant
      abutments and nickel-chromium superstructures.
AB  - PURPOSE: The objectives of this study were to evaluate the galvanic corrosion
      behavior between titanium and nickel-chromium (Ni-Cr) alloy, to investigate the
      effect of diamondlike carbon (DLC) coating over titanium on galvanic corrosion
      behavior between titanium and Ni-Cr alloy, and to evaluate the effect of DLC
      coating over titanium abutments on the fit and integrity of prosthetic assemblies
      by scanning electron microcopy (SEM). MATERIALS AND METHODS: Five Ni-Cr and 10
      titanium disks with a diameter of 5 mm and thickness of 3 mm were prepared. DLC
      coating was applied to five titanium disks. Electrode samples were prepared, and
      open circuit potential measurements, galvanic current measurements over platinum
      electrodes, and potentiodynamic polarization tests were carried out. For the SEM
      evaluation, 20 Ni-Cr alloy and 10 gold alloy superstructures were cast and
      prepared over 30 abutments. DLC coating was applied to 10 of the abutments.
      Following the fixation of prosthetic assemblies, the samples were embedded in
      acrylic resin and cross sectioned longitudinally. Internal fit evaluations were
      carried out through examination of the SEM images. RESULTS: Titanium showed more
      noble and electrochemically stable properties than Ni-Cr alloy. DLC coating over
      the cathode electrode served as an insulating film layer over the surface and
      prevented galvanic coupling. Results of the SEM evaluations indicated that the
      DLC-coated and titanium abutments showed no statistically significant difference
      in fit. Hence, no adverse effects on the adaptation of prosthetic components were
      found with the application of DLC coating over abutment surfaces. CONCLUSIONS:
      DLC coating might serve as a galvanic corrosion barrier between titanium
      abutments and Ni-Cr superstructures.

PMID- 23869363
TI  - Surgical techniques for alveolar socket preservation: a systematic review.
AB  - PURPOSE: To evaluate, through a systematic review of the literature, the efficacy
      of different surgical techniques in maintaining residual bone in the alveolar
      process following tooth extractions. MATERIALS AND METHODS: MEDLINE/PubMed was
      searched through January 2010 and papers were selected according to the CONSORT
      statement and an independent three-stage screening process. The selected outcome
      variables were clinical width and height changes of the socket, and means and
      standard deviations were calculated from the included studies. For those studies
      that were randomized controlled trials, six meta-analyses were performed by
      dividing studies into three groups with regard to the use of barriers and
      grafting (barriers alone, graft alone, or both). RESULTS: Thirteen papers met the
      eligibility criteria and were included in the analyses. Statistically significant
      ridge preservation was found for studies that used barriers alone; the pooled
      weighted mean was 0.909 mm (95% confidence interval, 0.497554 to 1.320732 mm) for
      bone height, while the mean for bone width was 2.966 mm (95% confidence interval,
      2.334770 to 3.598300 mm). CONCLUSIONS: Socket preservation procedures are
      effective in limiting horizontal and vertical ridge alterations in postextraction
      sites. The meta-analysis indicates that the use of barrier membranes alone might
      improve normal wound healing in extraction sites.

PMID- 23869364
TI  - A new approach to maintenance of regenerated autogenous bone volume: delayed
      relining with xenograft and resorbable membrane.
AB  - PURPOSE: The aim of this case series is to propose an approach to help maintain
      autogenous bone grafts. This is done by applying a collagen membrane (CM) and
      anorganic bovine bone (ABBM) at the time of implant surgery, rather than at the
      time of ridge augmentation, to avoid volume loss after implants are inserted.
      MATERIALS AND METHODS: Ten patients with severe horizontal bone atrophy were
      consecutively enrolled in this study. A staged approach was chosen for implant
      placement following horizontal ridge augmentation. A block graft was harvested
      from the retromolar area and secured to the recipient site with fixation screws;
      contour overbuilding was avoided. The width of the ridge was measured before and
      after horizontal augmentation. After 4 months of healing, implants were inserted,
      the augmented site was relined with ABBM, and CM was applied to prevent bone
      volume loss. Another 4 months later, at the time of abutment placement, cone beam
      computed tomography was performed to quantify the end result. RESULTS: The mean
      horizontal ridge width prior to treatment was 2.1 +/- 0.5 mm. Mean postsurgical
      crest width was 6.9 +/- 0.5 mm. After the 4-month healing period, the mean
      alveolar crest width was 6.6 +/- 0.6 mm. At the time of abutment connection, the
      mean width of the regenerated ridge, as measured on three-dimensional cone beam
      images, was 7.7 +/- 0.8 mm. CONCLUSIONS: Minimal bone loss occurred in
      unprotected autogenous bone grafts with respect to alveolar bone contour (0.25 +/
      0.29 mm). After the implants were inserted, no further remodeling/resorption
      occurred with sites treated by ABBM and CM relining; moreover, an additional
      increase in alveolar crest width was evident. The nonresorbable ABBM
      osseointegrated clinically and radiologically, preventing bone loss prior to
      implant loading. This layer appeared to maintain the regenerated crest volume.

PMID- 23869365
TI  - In vitro radiographic detection of cement overhangs on cement-retained implant
      restorations.
AB  - PURPOSE: The aim of this in vitro study was to investigate the potential of
      digital and conventional radiography to detect small amounts of residual dental
      luting cements around implant abutments. MATERIALS AND METHODS: Artificial cement
      and aluminum overhangs in varying thicknesses, heights, and depths were
      radiographed adjacent to implant restorations with a radiovisiography sensor.
      Five trained evaluators were asked to identify the smallest depth of overhang
      that could be detected on radiographs. RESULTS: For detection of cement overhangs
      adjacent to implant abutments, a luting agent must have greater radiopacity than
      what is recommended by relevant International Organization for Standardization
      directives. To detect a 0.1-mm-thick portion of excess cement adjacent to an
      implant abutment, the cement should have a radiopacity of at least 1.7 mm of
      aluminum for high-resolution digital radiographs and 2.2 mm of aluminum for film
      based radiographs. Two-way analysis of variance revealed that the thickness of
      the specimens, type of imaging detector, and type of cement all affected the
      radiopacity threshold for artificial cement excess (P < .05). The height of the
      specimens and the surrounding structures were not statistically significant
      factors in cement detection. CONCLUSIONS: Digital radiography offers better
      possibilities for visualization of cement excess than conventional radiography.

PMID- 23869366
TI  - The effectiveness of barrier membranes on bone regeneration in localized bony
      defects: a systematic review.
AB  - PURPOSES: The aim of this study was to assess the effectiveness of barrier
      membranes in bone augmentation through a systematic review of the literature.
      MATERIALS AND METHODS: Electronic data banks and hand searching were used to find
      relevant articles on the reconstruction of localized bone defects published up to
      May 2011. Controlled animal and human studies with more than 4 weeks of follow-up
      were included; studies of periodontal lesions, extraction sockets, and maxillary
      sinus grafts were excluded. Applications of recombinant growth factor or
      assessments of membranes' effects on implant osseointegration were also
      considered exclusion criteria. Defects filled with bone graft/bone substitute
      material and covered with a membrane were considered the test group, while
      uncovered defects were considered the control group. Thereafter, human and animal
      studies were evaluated separately by meta-analysis. RESULTS: Of the 3,986
      articles found in the initial search, 34 studies met the inclusion criteria. Four
      animal studies concluded that the use of barrier membranes would increase the
      amount of vertical augmented bone (mean difference 0.32 mm; P = .006).
      Qualitative results regarding horizontal bone augmentation were controversial.
      Membranes do not increase the risk of improper healing, according to both human
      studies (odds ratio 5.67; P = .32) and animal studies (odds ratio 3.35; P = .12).
      CONCLUSION: There is limited evidence to support the effectiveness of barrier
      membranes in the treatment of bone deficiencies. Membranes do not increase
      postoperative infection, wound dehiscence, or membrane/bone graft exposure in
      either human or animal models. Because a majority of the results are based on
      animal studies, more randomized clinical trials are needed to objectively measure
      the efficacy of membranes in human bone augmentation.

PMID- 23869367
TI  - Rehabilitation of children with ectodermal dysplasia. Part 1: an international
      Delphi study.
AB  - PURPOSE: An international Delphi study was undertaken to determine by consensus
      an agreed approach to the management of children with dental manifestations of
      ectodermal dysplasia, including the use of dental implants. This was done using a
      questionnaire developed by an interdisciplinary team. MATERIALS AND METHODS: The
      Delphi study questionnaire was built around 19 areas of clinical relevance and
      included 90 items. Topic areas included dental disability; initial diagnosis;
      global disability; oral health aspects of dental treatment (orthodontics,
      hypodontia, anodontia, implants); and case studies of selected treatment options.
      Eleven teams from six countries contributed to three iterations of the
      questionnaire. An algorithm was designed to standardize analysis of the
      questionnaire answers, all of which were blinded to ensure anonymity. The second
      and third rounds of the questionnaire excluded previously agreed-upon items but
      included the responses to the questions from the earlier rounds. The nonconsensus
      items inquired about the use of radiographs at initial diagnosis; sedation of an
      uncooperative child; use of a pretreatment questionnaire; the age range for
      specific treatments (eg, dentures, orthodontics, implants); specific uses of
      implants (eg, partial prostheses, overdentures, cantilevered prostheses); and
      case study 2. The residual nonconsensus questions were subsequently discussed at
      a 2-day meeting. RESULTS: Among the 90 questions and partial questions, there was
      progressive consensus, with agreements in rounds 1, 2, and 3 of 61%, 21%, and 8%,
      respectively. At the conclusion of round 3, there was 90% agreement and it was
      considered that the nonconsensus items required in-depth face-to-face discussion
      at a consensus meeting, which is described in part 2 of the study. CONCLUSION:
      The Delphi study provided an opportunity to engage specialist teams in recognized
      centers to integrate their clinical knowledge and draw on published data to
      develop a consensus of evidence-based responses.

PMID- 23869368
TI  - Rehabilitation of children with ectodermal dysplasia. Part 2: an international
      consensus meeting.
AB  - A consensus meeting was arranged to provide an opportunity to discuss the
      residual nonconsensus questions following three rounds of a Delphi study. It was
      hoped that the nonagreements could be resolved to define a comprehensive protocol
      for the management of ectodermal dysplasia, particularly with respect to the use
      of dental implants in growing patients. An international panel of expert
      clinicians in pediatric dentistry, prosthodontics, and orthodontics was invited
      to be part of the Delphi study to develop agreement on clinical questions through
      a consensus of ideas. Each expert had been invited to form a study group or team
      within his or her home institution. As required by the Delphi protocol, a 90-part
      questionnaire was considered by the collaborating teams and progressed through
      three iterations with increasing agreement. This process is discussed in part 1
      of the study. The residual nonconsensus questions, which represented 10% of the
      questionnaire, required collaborative interaction for resolution. The consensus
      meeting was held in London, England, over a 2-day period with support from Nobel
      Biocare and the British Dental Association. 

PMID- 23869369
TI  - Comparative clinical study of three-unit fixed partial prostheses supported by
      two or three implants.
AB  - PURPOSE: To compare clinical outcomes of three-unit fixed prostheses supported by
      two or three implants in the posterior region. MATERIALS AND METHODS: Patients in
      this retrospective study were restored with three-unit fixed partial prostheses
      supported by two (group 1) or three (group 2) implants in the partially
      edentulous posterior maxilla and mandible. Outcome measures were survival and
      success rate, marginal bone loss, complication rate, and peri-implant soft tissue
      indices. Two-way ANOVA and an independent t test were performed at a significance
      level of P < .05. RESULT: A total of 48 implants placed in 23 patients (group 1)
      and 132 implants placed in 40 patients (group 2) were observed for 52.9 +/- 19.7
      months and 58.5 +/- 22.0 months, respectively. Both groups showed a 100% survival
      rate. The success rate, considering marginal bone loss, was 82% (group 1) and 86%
      (group 2). Marginal bone loss was greater in group 1 every year during 3 years of
      measurement, but the difference was not statistically significant (P > .05).
      Differences of marginal bone loss according to sex, anatomical location (maxilla
      vs mandible), and connection type (external vs internal) also were not
      significant (P > .05). Complication rates were similar, but Plaque Index was
      significantly greater in group 2 (P < .05). CONCLUSION: Within the limitations of
      this study, three-unit fixed partial prostheses supported by two implants showed
      comparable clinical outcomes with those supported by three implants in the
      partially edentulous posterior maxilla and mandible during the short- to medium
      term.

PMID- 23869370
TI  - Immediate versus conventional loading for the maxilla with implants placed into
      fresh and healed extraction sites to support a full-arch fixed prosthesis:
      nonrandomized controlled clinical study.
AB  - PURPOSE: To compare immediate and conventional loading of fixed full-arch
      maxillary prostheses supported by implants placed in healed and fresh
      postextraction sites. MATERIALS AND METHODS: This prospective, controlled,
      nonrandomized 12-month study included 30 consecutive patients requiring fixed
      full-arch maxillary prostheses supported by implants placed in healed and fresh
      extraction sites. Fifteen patients were treated with conventional loading
      (control group), and 15 were treated with immediate loading (test group). Each
      patient received six to eight implants; implants with insertion torque < 35 Ncm
      were conventionally loaded and excluded from the analysis. Implant success,
      biologic and prosthetic complications, success of the immediately loaded
      provisional prostheses, and marginal bone loss were assessed and analyzed
      statistically. RESULTS: One test group patient failed to attend recall visits and
      was excluded from the study, and 16 implants did not achieve insertion torque of
      35 Ncm and were excluded from analyses. The final sample included 29 patients and
      193 implants (94 test implants, 99 control implants). Implant success rates were
      96.8% (test) and 99.0% (control). In the test group, the most common
      complications were screw loosening and tooth fractures; in the control group,
      dentures caused discomfort and soft tissue irritation. The success rate of the
      immediately loaded prostheses was 100%. Average bone loss was 0.61 +/- 0.21 mm
      for test implants and 0.53 +/- 0.18 mm for control implants. Differences between
      loading protocols were not statistically significant. CONCLUSIONS: No significant
      differences in implant success and peri-implant marginal bone loss were seen in
      the current 12-month comparison of immediate and conventional loading of
      maxillary fixed full-arch prostheses. Biologic and prosthetic complications were
      rare with both loading protocols, and all immediately loaded provisional fixed
      prostheses performed successfully.

PMID- 23869371
TI  - Long-term effect of overdenture bar design on peri-implant tissues.
AB  - PURPOSE: To evaluate factors promoting mucositis and peri-implantitis (plaque
      accumulation, poor peri-implant soft tissue health, bone loss) with regard to
      prosthetic attachment systems consisting of implant-supported bar-retained
      overdentures. MATERIALS AND METHODS: Patients who received TiOblast implants to
      support overdentures retained by either (1) prefabricated bars with or without
      extensions or (2) cast bars were recalled and examined clinically and
      radiographically. Plaque Index (PI), Sulcus Bleeding Index (SBI), probing pocket
      depth (PPD), and peri-implant bone loss were measured. Peri-implant tissue health
      was assessed, and the presence of mucositis and peri-implantitis was recorded.
      One-way analysis of variance with the Bonferroni adjustment was used to compare
      groups (alpha = .05). RESULTS: Five to 10 years after prosthetic loading, 107
      patients who received 516 TiOblast implants were evaluated; 31 of these patients
      were treated with 131 implants to support bar-retained overdentures. PI, SBI,
      PPD, and pathologic bone loss were least common in the group with prefabricated
      bars, followed by the group with prefabricated bars with extensions, and were
      most common in the group with cast bars. Plaque accumulation and pathologic bone
      loss values were higher with implants that supported mandibular bar-retained
      overdentures than with those supporting maxillary bar-retained overdentures.
      However, these differences among attachment systems or between maxillary and
      mandibular implants were not significant (P > .05). Mucositis was observed in one
      implant in the group with prefabricated bars, four implants in the group with
      prefabricated bars with extensions, and four implants in the group with cast
      bars. Peri-implantitis was observed in one implant of the cast bar group.
      CONCLUSIONS: Five to 10 years after prosthetic loading, no significant difference
      in PI, SBI, PPD, pathologic bone loss, or peri-implant tissue conditions among
      the different bar designs tested was observed.

PMID- 23869372
TI  - Clinical performance and peri-implant parameters of 132 implants supporting
      locator-retained overdentures: a case series of 33 patients.
AB  - PURPOSE: The aim of this study was to assess the long-term reliability of Locator
      retained mandibular or maxillary overdentures and to examine clinical and
      radiographic parameters of the supporting implants. MATERIALS AND METHODS: The
      authors performed a retrospective analysis of a case series. After implant
      placement and a submerged healing phase of about 3 months, all implants were
      restored with Locator-retained overdentures. The follow-up examinations included
      the assessment of the Plaque Index (PI) and sulcus Bleeding Index (SBI) as well
      as peri-implant soft tissue parameters, such as bleeding on probing (BOP) and
      pocket probing depth (PPD). The mean marginal bone loss was measured on panoramic
      radiographs. The clinical performance of Locator components and the prosthetic
      restoration were evaluated. Descriptive statistics were computed. For statistical
      analysis, non-parametric and parametric tests with respect to the variable scale
      were used. The significance level was set as P <= .05. RESULTS: The sample was
      composed of 33 patients (18 men, 15 women) with a mean age of 66.8 years who
      received 132 implants (84 in the anterior maxilla, 48 in the anterior mandible).
      After 32.9 months of follow-up, one maxillary implant was lost. All prosthetic
      restorations were still functionally in place at the last follow-up appointment
      with moderate prosthodontic maintenance effort. Clinical parameters and
      radiographs revealed healthy tissues around most implants. CONCLUSION: Within the
      limitations of this study, it can be concluded that Locators are a predictable
      alternative for anchorage of mandibular and maxillary overdentures with good
      clinical performance of both the prosthetic restorations and the supporting
      implants.

PMID- 23869373
TI  - Palatal positioning of implants in severely atrophic edentulous maxillae: five
      year cross-sectional retrospective follow-up study.
AB  - PURPOSE: To evaluate the 5-year outcome of a previously reported case series of
      patients with severely atrophic maxillae treated with palatally positioned
      implants and fixed full-arch rehabilitations. MATERIALS AND METHODS: A
      retrospective cross-sectional clinical study of patients treated between January
      2000 and January 2004 with palatally positioned implants was carried out. The
      parameters evaluated at the 5-year follow-up visit were: implant success rate,
      peri-implant soft-tissue conditions, biological and prosthetic post-loading
      complications, radiographic peri-implant marginal bone loss, and patient
      satisfaction. RESULTS: A total of 33 patients with 151 palatally positioned
      implants were included in the study; 15 patients had received cemented prostheses
      and 18 had received screwed full-arch prostheses. The success rate for palatally
      positioned implants after 5 years was 98.7%. Average peri-implant mucosa
      retraction was 0.39 +/- 0.94 mm and the average probing depth was 2.89 +/- 0.77
      mm. Plaque Index was 0 in 63.1% of the implants, 1 in 18.8%, 2 in 8.7%, and 3 in
      9.4%. The modified Bleeding Index was 0 in 71.1%, 1 in 14.1%, and 2 in 14.8%.
      Mucositis was found in 5.2% of the implants and none had peri-implantitis.
      Prosthetic complications occurred in 12.1% of the cases. Average peri-implant
      marginal bone loss was 1.03 +/- 1.28 mm. General patient satisfaction averaged
      8.2 +/- 1.8 according to a 10-point visual analog scale, and good quality of life
      was reported by most patients. CONCLUSIONS: Palatally positioned implants were
      found to be an adequate treatment for patients with severely atrophic maxillae. A
      high implant success rate, good peri-implant soft tissue stability, low marginal
      bone loss, high patient satisfaction and few complications were registered.

PMID- 23869374
TI  - Vertical fracture and marginal bone loss of internal-connection implants: a
      finite element analysis.
AB  - PURPOSE: Marginal bone loss around implants is of great concern, and its cause
      may be multifactorial. Recently, clinical cases presenting marginal bone loss, in
      most cases accompanied by vertical fracture of internal-connection implants in
      the buccolingual direction, have been reported, in which unfavorable stress
      distribution is one possible cause of marginal bone resorption. The purpose of
      the current study was to characterize this type of marginal bone loss and implant
      fracture by conducting a finite element analysis (FEA). MATERIALS AND METHODS:
      Clinical and radiographic evaluations showed that the prostheses of all reported
      cases had implant-level setups and were directly screwed to the internal
      implants. Intriguingly, all vertical fractures reported were in the buccolingual
      direction. Therefore, to characterize the specific implant fractures, FEA was
      conducted with misfit models created for two different setups, abutment-level and
      implant-level, both with screw-retained prostheses. The models were subjected to
      initial misfits of 0 MUm (representing perfect fit), 50 MUm, 100 MUm, 150 MUm, or
      200 MUm, and vertical loading was then applied. RESULTS: FEA revealed that, for
      the implant-level setup, excessive stress at the neck of the implant gradually
      increased in the buccolingual direction as the misfit increased. This result was
      not seen for the abutment-level setup. A broad maximum stress distribution was
      evident for the implant-level setup but not for the abutment-level setup.
      CONCLUSION: Broad distribution of excessive stress in the FEA correlated to the
      clinical cases, and marginal bone loss in these cases may be associated with
      mechanical alterations. To avoid unnecessary complications, selection of an
      abutment-level setup is strongly suggested.

PMID- 23869375
TI  - Finite element comparison of 10 orthodontic microscrews with different cortical
      bone parameters.
AB  - PURPOSE: Unlike standard dental implants, the stabilization of orthodontic
      microscrews removed after treatment is done without osseointegration and achieved
      by several components: cortical bone thickness (CBT), microscrew geometry, and
      drilling depth. The purpose of this study was to evaluate 10 different
      microscrews and the influence of their geometric parameters with different CBT
      and drilling depths. MATERIALS AND METHODS: The influence of geometric parameters
      in cortical bone was analyzed with a series of computational simulations with
      finite element models to obtain von Mises stresses and deformations in the
      microscrew when loaded with a perpendicular traction force of 1 N and considering
      the angle of incidence as a random parameter. RESULTS: There was variability in
      the angle of incidence, with less clinical influence. Biomechanical parameters
      such as microscrew diameter, CBT, and drilling depth had significant influences
      on the results. At a drilling distance of 8 mm, narrow microscrews (Abso Anchor
      1.2) showed maximum von Mises stress of 500.698 MPa and maximum deformation in
      the shank of 0.08549 mm. Microscrews with a diameter of 1.5 mm (Dentaurum, Jeil,
      Mondeal, Tekka, Spider) showed von Mises stresses ranging from 56.97 to 136 MPa
      and deformation between 0.0062055 and 0.0476 mm. Microscrews with a diameter of
      2.0 mm (Jeil, Mondeal, Tekka) showed von Mises stresses ranging from 17.172 to
      54.861 MPa and deformation of 0.000172 to 0.0161 mm. CONCLUSIONS: The shape and
      geometry of an orthodontic microscrew are highly important in its behavior.
      Optimal characteristics of a microscrew would include a diameter of 2.0 mm, a
      cylindric shape, a short and wide head, a short and wide shank, and threads of an
      appropriate size.

PMID- 23869376
TI  - Peri-implant bone response around a human hydroxyapatite-coated implant retrieved
      after a 10-year loading period: a case report.
AB  - This case report presents a histologic and histomorphometric evaluation of the
      peri-implant tissues of a HA-coated implant retrieved due to peri-implantitis
      after a 10-year loading period. The implant was retrieved with a trephine and
      treated to obtain thin ground sections. At low-power magnification mostly
      compact, mature bone with small marrow spaces could be observed at the interface
      with the implant. The coating was always present in the areas where bone was
      detected, the bone was always in close contact with the coating, and there was no
      detachment between the metal and coating or between the coating and bone. Areas
      of bone remodeling were demonstrated by the presence of many secondary osteons
      and reversal lines close to the implant surface. The bone-implant contact
      percentage was 36.3% +/- 1.2%. The percentage of the implant surface covered by
      the HA coating without bone, where bone may have detached during retrieval, was
      32.6% +/- 2.8%. This HA-coated implant, continued to demonstrate more than
      adequate BIC after many years of function and the potential to maintain
      osseointegration in the long term. 

PMID- 23869377
TI  - A dental implant in the infratemporal fossa: case report.
AB  - This case report describes a rare displacement of a dental implant in the
      infratemporal fossa, which occurred during placement of the implant into the
      pterygoid process with computer-assisted technology. The implant was immediately
      removed by means of an intraoral approach to prevent any neurologic
      complications. Although computer-aided systems in implant surgery represent a
      reliable and effective tool, the surgeon should always instruct the patient on
      the necessary behavior during implant placement and the risks associated with a
      lack of adherence to these recommendations. 

PMID- 23869378
TI  - Metal-tag labeling coupled with multiple reaction monitoring-mass spectrometry
      for absolute quantitation of proteins.
AB  - Mass spectrometry-based quantitative proteomics, consisting of relative and
      absolute parts, has been used to discover and validate proteins with key
      functions related to physiological and pathological processes. Currently, stable
      isotope dilution-multiple reaction monitoring-mass spectrometry (SID-MRM-MS) is
      the most commonly used method for the absolute determination of proteins in a
      biological sample. A prerequisite for this method is obtaining internal standards
      with isotope labels. Although many approaches have been developed for the
      labeling and preparation of internal peptides, expensive stable isotope labeling
      coupled with SID-MRM-MS has limited the application and development of an
      absolute quantitative method. Recently, a low-cost strategy using metal-tag
      labeling and MS has been developed for relative quantification of peptides or
      proteins. The introduction of labeling using metal tags has the merits of
      allowing multiple labeling and enlarging the mass shift to overcome the overlap
      of adjacent isotope clusters. However, most papers described MRM-MS for protein
      absolute quantification based on the metal in its peptides labelled with metal by
      inductively coupled plasma mass spectrometry (ICP MS) but not on its peptides
      labelled with metal. In this work, a novel approach based on metal-tag labeling
      coupled with MRM-MS was established for the absolute quantification of peptides
      or proteins. The principle of the method is that a bifunctional chelator,
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid bearing an N
      hydroxysuccinimide ester (DOTA-NHS ester), is used to modify the N-termini of
      signature peptides from a target protein, and the modified peptides then chelate
      a certain metal, such as thulium, to form metal-tagged peptides (Tm-DOTA-P).
      Internal peptides are chemically synthesized and labeled with another metal, such
      as terbium (Tb-DOTA-P), as the internal standard. Both the Tb-DOTA- and Tm-DOTA
      labeled peptides in samples can be analysed via MRM-MS. The experimental results
      show that the accuracy (%RE) and precision (%RSD) of the approach are both below
      15%, and the lower limit of quantification (LOQ) is 0.8 fmol MUL(-1), with good
      linearity (R(2) > 0.99) observed covering the range of 2 orders of magnitude.
      Furthermore, one protein, enolase, in an extract from Thermoanaerobacter
      tengcongensis was successfully quantified, which demonstrates that this novel
      absolute quantification method is a new strategy for simple, rapid, low-cost and
      accurate absolute protein quantification in a complex biological sample. 

PMID- 23869379
TI  - Ambient pressure thermal desorption ionization mass spectrometry for the analysis
      of substances of forensic interest.
AB  - The large backlog of forensic samples needing chemical analysis requires new
      tools with high specificity, throughput, and reliability. Mass spectrometric
      techniques have the specificity and reliability necessary for identification, but
      often require sample preparation before analysis. The growth of ambient pressure
      ionization techniques has the capability to reduce the need for lengthy
      preparation. This report presents one possible technique, ambient pressure
      thermal desorption ionization mass spectrometry, which could prove to be useful
      to the forensic science community. Example mass spectra for several explosive
      compounds and illicit drugs obtained from liquid and bulk samples with almost no
      sample preparation are presented. The use of the technique for quantitative
      analysis is also addressed. 

PMID- 23869380
TI  - Single molecular dissection of the ligand binding property of epidermal growth
      factor receptor.
AB  - The understanding of ligand binding interactions is an important component of
      understanding the fundamental mechanism of receptor function. In this study, the
      binding abilities of EGF and TGF-alpha to EGFR on human bladder cancer (T24)
      cells were investigated by single molecular force spectroscopy (SMFS) based on
      atomic force microscopy (AFM). By approaching the specifically functionalized AFM
      tips to the T24 cell surface and subsequent retraction, specific unbinding events
      of the EGF/EGFR complexes and TGF-alpha/EGFR complexes were investigated.
      Further, the unbinding forces and the kinetic off rate constants that govern the
      bond stabilities were calculated through varying the external mechanic forces
      applied. Meanwhile, the distances from the energy minimum to the transition
      states along the separation paths of the EGF/EGFR complexes and TGF-alpha/EGFR
      complexes were deduced. This study at single-molecule level may enrich our
      understanding of the ligand binding properties of EGFR and provide some new
      information to the development of improved EGFR inhibitors. In addition, the
      results present new insight into the study of the energy landscape of the
      dissociation of ligand-EGFR system. 

PMID- 23869381
TI  - One-step synthesis of an organic-inorganic hybrid boronate affinity monolithic
      column with synergistic co-monomers.
AB  - An organic-inorganic hybrid and synergistic boronate affinity (BA) monolithic
      column was synthesized by a novel "one-step" approach. We report on the synthesis
      of a unique organic-inorganic hybrid affinity monolith by using TEOS, the organic
      silane, N-(beta-aminoethyl)-gamma-aminopropyltriethoxysilane (AEAPTES) and gamma
      MAPS as the co-precursors, 4-vinylphenylboronic acid as the functionalized
      monomer, and azobisisobutyronitrile (AIBN) as the initiator. Due to the presence
      of amino groups in the AEAPTES molecule, the prepared monolith exhibits several
      attractive properties. The monolith will be more hydrophilic and can bind with
      cis-diol compounds at neutral pH by a mechanism of intermolecular B-N
      coordination. The resulting hybrid boronate affinity monoliths have potential
      applications in specific recognition and enrichment of cis-diol biomolecules
      under neutral conditions. 

PMID- 23869382
TI  - A simple green route to prepare stable silver nanoparticles with pear juice and a
      new selective colorimetric method for detection of cysteine.
AB  - In this work, a new cost-effective, rapid and simple method for the preparation
      of stable silver nanoparticles (AgNPs) was developed, which can be completed
      within 15 minutes at room temperature by oxidizing the reductants in pear juice
      with AgNO3. Compared with the most used citrate-capped AgNPs, the as-prepared
      AgNPs showed high stability, good biocompatibility and enhanced antibacterial
      activity. Based on the formation of Ag-S covalent bonds between cysteine and
      AgNPs as well as the electrostatic interaction of COO(-) and NH4(+) between
      cysteine molecules, which selectively lead to the aggregation of the as-prepared
      AgNPs and give a specific yellow-to-red colour change, a new selective
      colorimetric method for detection of cysteine was proposed with the as-prepared
      AgNPs by coupling the decrease of the characteristic localized surface plasmon
      resonance (LSPR) absorption at 406 nm of the as-prepared AgNPs and the increase
      of the new aggregation-induced band at 530 nm. The ratio of the absorbance at 530
      nm to 406 nm (A530/A406) was found to be linearly dependent on the cysteine
      concentrations in the range of 5.0 * 10(-7) to 1.0 * 10(-5) M with a limit of
      detection of 6.8 * 10(-8) M. 

PMID- 23869383
TI  - Controlled biohybrid nanoprobes with silver nanoparticle clusters for Raman
      imaging.
AB  - A new class of biohybrid nanoprobes has been developed for surface-enhanced Raman
      scattering-based bioimaging. Silver nanoparticle clusters were encapsulated in
      polymeric nanoparticles using electrohydrodynamic jetting, followed by
      stabilization and bioconjugation. Controlled SERS intensity with high
      sensitivity, chemical stability, and biocompatibility makes the SERS biohybrid
      nanoprobes useful for bioimaging. 

PMID- 23869384
TI  - Energy-selective neutron imaging for morphological and phase analysis of iron
      nickel meteorites.
AB  - We propose energy-selective neutron imaging as a new and non-destructive method
      to investigate rare metallic meteorites. It is based on attenuation of a neutron
      beam of limited spectral distribution in a sample depending on the elemental
      composition and crystalline structure. Radiography and tomography allow obtaining
      the presence, morphology and orientation information in the bulk of mineral
      inclusions, oxide crust and crystalline structure. Its usage in classification
      and meteor formation studies would be of great value. 

PMID- 23869385
TI  - A label-free and colorimetric turn-on assay for coralyne based on coralyne
      induced formation of peroxidase-mimicking split DNAzyme.
AB  - A simple, label-free and colorimetric method for coralyne detection was
      successfully established based on the coralyne-induced formation of split G
      quadruplex-hemin DNAzyme. It can achieve a detection limit of 31 nM toward
      coralyne with excellent selectivity. 

PMID- 23869386
TI  - Multiplexed DNA detection with a composite molecular beacon based on guanine
      quenching.
AB  - We developed a multiplexed DNA detection method with a composite molecular beacon
      (MB) probe based on guanine-quenching by synchronous fluorescence analysis. It is
      demonstrated by two types of tumor-suppressor genes namely exon segments of p16
      (T1) and p53 (T2) genes. The composite MB probe includes two loops and two stems,
      and two fluorophores of 6-carboxyfluorescein group (FAM) and tetramethyl-6
      carboxyrhodamine (TAMRA) are connected to the two ends of molecular beacon. Every
      stem portion of MB include four continuous nucleotides with guanine (G) base as
      quencher, every loop portion is a probe sequence that is complementary to a
      corresponding target sequence. In the absence of target DNA, the composite MBs
      are in the stem-closed form, the fluorescence of FAM and TAMRA are quenched by G
      bases. At this time, the fluorescence signals of FAM and TAMRA are all very low.
      In the presence of target DNA, the MBs hybridize with the target DNA and form
      double-strands, FAM and TAMRA are separated from G bases, and the fluorescence of
      FAM and TAMRA recovers simultaneously. Thus, the simultaneous detection of two
      targets of DNA can be realized by measuring fluorescence signals of FAM and
      TAMRA, respectively. Under the optimum conditions, the fluorescence intensities
      of FAM and TAMRA all exhibit good linear dependence on their target DNA
      concentration in the range from 5 * 10(-11) to 5.5 * 10(-9) M. The detection
      limit of T1 is 4 * 10(-11) M (3sigma), and that of T2 is 3 * 10(-11) M. This
      composite MB can be applied to detect the real sample, and can be applied to
      detect two aleatoric sequences of DNA. Compared with previously reported methods
      of detecting multiplexed target DNA with MBs, the proposed method has some
      advantages including easy synthesis of composite MB probes, low detection cost
      and shorter analytical time. 

PMID- 23869387
TI  - Employing bifunctional enzymes for enhanced extraction of bioactives from plants:
      flavonoids as an example.
AB  - A cost-effective and environmentally friendly approach was developed to improve
      the extraction of active ingredients from plants, in which a bifunctional enzyme
      was employed for not only facilitating cell wall degradation but also increasing
      the bioactivity of target compounds in the extract. In the aqueous extraction of
      flavonoids from Glycyrrhizae radix, Trichoderma viride cellulase, a commercial
      cell-wall-degrading enzyme, was found to efficiently deglycosylate liquiritin and
      isoliquiritin, which are of high content but low bioactivity, into their
      aglycones that have much higher physiological activities for dietary and
      medicinal uses. Under optimized conditions, the extraction yield of
      liquiritigenin and isoliquiritigenin aglycones reached 4.23 and 0.39 mg/g of dry
      weight (dw) with 6.51- and 3.55-fold increases, respectively. The same approach
      was expanded to the extraction of flavonoids from Scutellariae radix using
      Penicillium decumbens naringinase, where enhanced production of more bioactive
      bacalein and wogonin was achieved via enzymatic deglycosylation of bacalin and
      wogonoside.

PMID- 23869388
TI  - A new cycloartane nortriterpenoid from stem and leaf of Quercus variabilis.
AB  - A new compound 3-acetyloxy-epicycloeucalenol-24-one (1), with 11 known compounds
      3alpha-acetyloxy-4alpha,14alpha-dimethyl-9beta,19-cycloergost-24-oic acid (2), 3
      epicycloeucalenol (3), 3-epicycloeucalenyl-24-one (4), 3-epicycloeucalenyl
      acetate (5), 4beta,14alpha-dimethyl-5alpha-ergosta-9beta,19-cyclo-24(31)-en-3beta
      hydroxy-4alpha-carboxylic acid (6), cycloeucalenone (7), friedelin (8),
      epifriedelanol (9), lup-20 (29)-en-3beta,30-diol (10), betulin (11), lupeol (12),
      was isolated from the stems and leaves of Quercus variabilis Blume. Seven
      compounds (1-7) showed anti-inflammatory activity. 

PMID- 23869389
TI  - I would like to live in Garrison Keillor's world where all the women are strong.
      Introduction.

PMID- 23869390
TI  - Disorders of childhood growth and development: failure to thrive versus short
      stature.
AB  - Failure to thrive (FTT) describes retarded growth in height and weight, whereas
      short stature (SS) involves comparison of a child or adolescent's height to that
      of a reference group or to his or her own height across time. To identify either
      condition in infants, children, and adolescents, the family physician should
      focus on accurate measurement of length/height and weight as well as careful
      plotting and assessment of the rate of linear growth and weight gain based on
      World Health Organization standards (from birth to 2 years) and Centers for
      Disease Control and Prevention charts (from age 2 years). Identification of the
      etiologies of FTT and SS is complex, requiring consideration of such factors as
      birth weight, prematurity, and familial height. FTT can result from inadequate
      caloric intake (eg, caused by difficulties with nursing, limited food
      availability, or incorrect formula preparation), inadequate caloric absorption
      (eg, resulting from metabolic, gastrointestinal, or other medical conditions), or
      excessive caloric expenditure/ineffective utilization (eg, due to
      hyperthyroidism, diabetes, pulmonary or cardiac conditions). Short stature can be
      due to a primary growth disorder, such as bone disease or chromosomal syndrome; a
      secondary factor, such as a chronic medical or endocrine disorder; or an
      undetermined etiology. The management of FTT and SS requires attention to a
      combination of medical and behavioral/social issues (eg, treating underlying
      conditions, assisting with the feeding process, addressing stress and social
      functioning), and often requires a multidisciplinary approach. 

PMID- 23869391
TI  - Disorders of childhood growth and development: childhood obesity.
AB  - The incidence of childhood obesity in the United States is estimated at 17%, or
      12 million children ages 2 to 19 years. Obesity is a multifactorial condition
      with syndromic and nonsyndromic variants. Genetic, social, ethnic,
      endocrinologic, and behavioral issues are all potential etiologic factors.
      Preventive efforts should begin with monitoring from birth and include
      breastfeeding until age 6 months, avoiding juices, and promoting fruit and
      vegetable consumption and adequate exercise. Childhood obesity is diagnosed based
      on body mass index; a child is considered overweight at the 85th to 95th
      percentiles and obese at or above the 95th percentile. After obesity is
      diagnosed, testing should include blood pressure levels, fasting lipid profile,
      diabetes screening, and liver function tests. The physician should obtain a
      detailed history of the physical activity level and food intake and assess
      possible complications of obesity, including depression and hypertension,
      annually. Lifestyle interventions with family involvement are the mainstay of
      management, with pharmacotherapy or bariatric surgery considered for adolescents
      only if intensive lifestyle modifications have failed and in the presence of
      comorbidities. Intervention by multiple disciplines (ie, medicine, nutrition,
      psychology) is recommended, and family physicians are encouraged to become more
      involved in encouraging physical activity and improved nutrition for children. 

PMID- 23869392
TI  - Disorders of childhood growth and development: precocious puberty.
AB  - Precocious puberty is defined as pubertal development that begins at an earlier
      age than expected; most US pediatric endocrinology subspecialists use cutoff ages
      of 8 years for girls and 9 years for boys. Early activation and maturation of the
      hypothalamic-pituitary-gonadal axis leads to hormonal changes, physical signs of
      puberty, and acceleration of linear growth. Factors affecting puberty include
      race/ethnicity, obesity, and endocrine disruptors. The 2 forms of precocious
      puberty are central (gonadotropin-dependent precocious puberty) and peripheral
      (gonadotropin-independent precocious puberty). Most cases of the former have no
      identifiable etiology, whereas the latter is caused by increased secretion of sex
      hormones by the gonads or adrenal glands. It is important to differentiate
      progressive from nonprogressive precocious puberty to avoid unnecessary treatment
      for the latter; if diagnosis is uncertain, the child should be reassessed within
      several months. Evaluation begins with a detailed history and physical
      examination followed by an x-ray for bone age; in precocious puberty, bone age is
      greater than chronologic age. If indicated, additional serum testing (basal
      luteinizing hormone) and imaging studies should be obtained. Patients should be
      referred to a pediatric endocrinology subspecialist for treatment. It is
      essential to manage underlying etiologies. Gonadotropin-releasing hormone
      agonists should be considered only for children with progressive central
      precocious puberty to prevent short stature. For children with apparent
      nonprogressive precocious puberty, follow-up every 3 to 6 months between ages 6
      and 7 years is recommended to assess for progression. 

PMID- 23869393
TI  - Disorders of childhood growth and development: screening and evaluation of the
      child who misses developmental milestones.
AB  - The family physician is one of the few individuals from whom families receive
      feedback about their children's development; this makes early identification of
      potential delays an important responsibility. The American Academy of Pediatrics
      recommends formal developmental screening for all children at the 9-, 18-, and 24
      and/or 30-month well-child visits as well as developmental surveillance at every
      office visit through age 5 years. A formal screening measure is recommended,
      taking into account administration time and cost, characteristics of the patient
      population (eg, availability of screening tool in numerous languages), and
      psychometrics (eg, reliability, sensitivity, specificity). In the case of
      abnormal screening results, family physicians must determine the need for further
      medical evaluation (eg, by a developmental pediatric subspecialist or a pediatric
      neurology, genetics, or physiatry subspecialist) and/or further developmental
      evaluation (eg, by a physical therapy [PT], occupational therapy [OT],
      speech/language pathology, psychology, or audiology subspecialist). Knowledge of
      early intervention and early childhood programs is necessary for directing
      parents to evaluation and treatment sources. In treating patients with
      developmental delays, family physicians must possess knowledge regarding
      traditional modalities (eg, speech/language therapy, OT, PT) as well as newer
      treatments with less research support (eg, gluten-free/casein-free diet,
      hyperbaric oxygen therapy, neurodevelopmental treatment) that families may
      consider. 

PMID- 23869394
TI  - Automatic event detection in lung transplant recipients based on home monitoring
      of spirometry and symptoms.
AB  - OBJECTIVE: The goal of this study was to develop, implement, and test an
      automated decision system to provide early detection of clinically important
      bronchopulmonary events in a population of lung transplant recipients following a
      home monitoring protocol. SUBJECTS AND METHODS: Spirometry and other clinical
      data were collected daily at home by lung transplant recipients and transmitted
      weekly to the study data center. Decision rules were developed using wavelet
      analysis of declines in spirometry and increases in respiratory symptoms from a
      learning set of patient home data and validated with an independent patient set.
      RESULTS: Using forced expiratory volume in 1 s or symptoms, the detection
      captured the majority of events (sensitivity, 80-90%) at an acceptable level of
      false alarms. On average, detections occurred 6.6-10.8 days earlier than the
      known event records. CONCLUSIONS: This approach is useful for early discovery of
      pulmonary events and has the potential to decrease the time required for humans
      to review large amount of home monitoring data to discover relatively infrequent
      but clinically important events.

PMID- 23869395
TI  - Information extraction for tracking liver cancer patients' statuses: from mixture
      of clinical narrative report types.
AB  - OBJECTIVE: To provide an efficient way for tracking patients' condition over long
      periods of time and to facilitate the collection of clinical data from different
      types of narrative reports, it is critical to develop an efficient method for
      smoothly analyzing the clinical data accumulated in narrative reports. MATERIALS
      AND METHODS: To facilitate liver cancer clinical research, a method was developed
      for extracting clinical factors from various types of narrative clinical reports,
      including ultrasound reports, radiology reports, pathology reports, operation
      notes, admission notes, and discharge summaries. An information extraction (IE)
      module was developed for tracking disease progression in liver cancer patients
      over time, and a rule-based classifier was developed for answering whether
      patients met the clinical research eligibility criteria. The classifier provided
      the answers and direct/indirect evidence (evidence sentences) for the clinical
      questions. To evaluate the implemented IE module and the classifier, the gold
      standard annotations and answers were developed manually, and the results of the
      implemented system were compared with the gold standard. RESULTS: The IE model
      achieved an F-score from 92.40% to 99.59%, and the classifier achieved accuracy
      from 96.15% to 100%. CONCLUSIONS: The application was successfully applied to the
      various types of narrative clinical reports. It might be applied to the key
      extraction for other types of cancer patients.

PMID- 23869396
TI  - Ethics and shared decision-making in paediatric occupational therapy practice.
AB  - BACKGROUND: Sharing information and decisions with children and their parents is
      critical in pediatric rehabilitation. Although the ethical significance and
      clinical benefits of sharing decisions are established, approaches for
      implementing shared decision-making in clinical practice are still developing.
      AIM: To explore the ethical challenges of sharing information and decisions with
      one family in pediatric occupational therapy. METHOD: We used a single
      qualitative in-depth interview with an occupational therapist to examine the
      ethical dimensions of sharing decisions. RESULTS: We found that asking what was
      ethically at stake in the information-sharing process, highlighted how timing and
      style of information sharing impacts on understanding and collaboration within
      the therapeutic relationship. Using ethics-based questions assisted in drawing
      out the complexity of implementing the ideals of sharing information and
      decisions in pediatric practice. CONCLUSION: Reflecting on ethical dimensions of
      communication with families assists to identify approaches to shared decision
      making in clinical practice.

PMID- 23869397
TI  - Variation in the microbiological quality of commercially produced vacuum-packed
      cooked sliced meat between production and the end of shelf-life.
AB  - A study of the microbiological quality of cooked, sliced vacuum-packed meat was
      undertaken. Three hundred and eighty-one samples were taken (127 sets of three
      samples) from 55 commercial premises that produced packets of sliced, cooked,
      vacuum-packed meat for retail sale. The set of three samples consisted of one
      from the unsliced, cooked meat, one from the sliced product immediately after
      slicing, and one sliced packet for end of shelf-life testing. Samples were
      examined for aerobic colony count (ACC), Enterobacteriaceae, Escherichia coli,
      Listeria, and Salmonella. When compared to current UK guidelines for the quality
      of ready to eat food, samples were found to be unsatisfactory for ACC,
      Enterobacteriaceae, and E. coli. Unsatisfactory rates increased at the end of
      shelf-life compared to the unsliced meat sample results. No samples were positive
      for Listeria monocytogenes or Salmonella. This data is important for producers
      setting the shelf-life of their products. 

PMID- 23869398
TI  - The yield and cost of colonoscopy in patients with metastatic cancer of unknown
      primary.
AB  - BACKGROUND: Although gastroenterologists are asked to perform colonoscopy in
      patients with metastatic cancer of unknown primary (MCUP), studies evaluating
      this practice are lacking. AIM: To determine the yield and cost of colonoscopy in
      patients referred for colonoscopy with an indication of MCUP. METHODS: We
      prospectively and retrospectively assessed colonoscopies performed from 2000 to
      2011 at a county, a university, and a Veterans Administration medical centre to
      identify patients referred for colonoscopy for the indication of MCUP. Exclusion
      criteria included overt or occult bleeding, iron-deficiency anaemia, familial
      colon-cancer syndrome, prior colon cancer, imaging suggesting colorectal lesion,
      and palpable rectal mass. Outcomes were the number of primary colon cancers and
      costs based on 2012 Medicare reimbursements. RESULTS: Two (1%) of the 160
      patients meeting enrollment criteria had a primary colon cancer identified, and
      both died within 1 month after diagnosis without receiving therapy targeted at
      colon cancer. One patient without colon cancer had a perforation because of
      colonoscopy, which required surgery and colostomy. The cost of a strategy of
      routinely performing colonoscopy in patients referred with MCUP was $84 736 per
      colon primary identified. CONCLUSIONS: Primary colon cancer was rarely identified
      at colonoscopy in patients with MCUP and no standard indications for diagnostic
      colonoscopy. Furthermore, the cost to diagnose one additional colon primary was
      very high. Those with colon cancer had advanced disease and were unable to
      benefit from targeted therapy. Routine colonoscopy for MCUP cannot be recommended
      at present.

PMID- 23869399
TI  - Potent antihypertensive activity of Thai-Lanna medicinal plants and recipes from
      "MANOSROI III" database.
AB  - CONTEXT: Traditional medicines have long been used by Thai practitioners for the
      treatment of many diseases including hypertension. The antihypertensive recipes
      and plants were searched and selected by a computer program from Thai/Lanna
      medicinal plant recipe database "MANOSROI III" using hypertensive symptoms as
      keywords. OBJECTIVES: To evaluate the antihypertensive potential of 30 recipes
      and 10 Thai-Lanna medicinal plants selected from "MANOSROI III" database using l
      NAME induced hypertensive rat model. MATERIALS AND METHODS: Extracts from the
      selected recipes and plants were prepared according to the traditional
      indications. Antihypertensive activities including the decrease of the mean
      arterial blood pressure (MABP) and heart rate (HR) of the extracts as well as
      duration of action were investigated by intra-arterial assessment technique. All
      extracts were screened for phytochemicals including anthraquinone, glycoside,
      xanthone, tannin, carotenoid, flavones and alkaloids using standard methods.
      RESULTS AND CONCLUSIONS: All 12 of the 30 selected recipes (40%) demonstrated
      antihypertensive activity with the maximum decrease of MABP at 27.17 +/- 3.17%
      that was 2.41-fold of prazosin hydrochloride. Most recipes exhibiting
      antihypertensive activity contained plants in the families of Zingiberaceae and
      Piperaceae. The top five antihypertensive recipes showed the presence of
      glycosides, xanthones and alkaloids. Ten single plants from these recipes were
      extracted and evaluated for antihypertensive activity. The cassumunar ginger
      extract exhibited the maximum decrease of MABP at 39.83 +/- 3.92%, which was 3.54
      times that of prazosin hydrochloride. This study demonstrated the potent
      antihypertensive activity of Thai medicinal plants and recipes that can be
      further developed as antihypertensive agents.

PMID- 23869400
TI  - Toll-like receptors and cytokines are upregulated during Helicobacter pylori
      infection in children.
AB  - BACKGROUND AND AIM: Helicobacter pylori infection is mainly acquired during
      childhood, and establishes a chronic infection that may lead to peptic ulcer or
      gastric cancer during adulthood. Toll-like receptors (TLRs) are expressed by
      distinct cell types throughout the gastrointestinal tract, and play an important
      role in regulation of the innate immune response. Few works have addressed TLRs
      expression in gastric epithelia of adults, and scarce studies have done it in
      children. The aim of this work was to analyze the expression of TLR2, TLR4, TLR5,
      TLR9, and IL-8, IL-10 and TNF-alpha in the gastric mucosa of children with and
      without H. pylori infection. METHODS: Gastric biopsies were collected by
      endoscopy from 50 children with recurrent abdominal pain, 25 with H. pylori
      infection and 25 without infection. In the gastric biopsies the expression of
      TLRs and cytokines was studied by immunohistochemistry, and the degree of mucosal
      inflammation was determined using the Sydney system. RESULTS: We found that H.
      pylori infection was associated with a significant increased expression of TLRs
      2, 4, 5 and 9, although expression varied between surface epithelia and glands.
      Epithelial cells expressing IL-8, IL-10 and TNF-alpha were increased in gastric
      mucosa of children with H. pylori infection. CONCLUSION: This study shows the
      gastric epithelia of children respond to H. pylori infection by increasing the
      expression of TLR2, TLR4, TLR5, TLR9 and the cytokines IL-8, IL-10 and TNF-alpha.

PMID- 23869401
TI  - Designed CVD growth of graphene via process engineering.
AB  - Graphene, the atomic thin carbon film with honeycomb lattice, holds great promise
      in a wide range of applications, due to its unique band structure and excellent
      electronic, optical, mechanical, and thermal properties. Scientists are
      researching this star material because of the development of various emerging
      preparation techniques, among which chemical vapor deposition (CVD) has received
      the fastest advances in the past few years. For the CVD growth of graphene, the
      ultimate goal is to achieve the highest quality in the largest scale and lowest
      cost with a precise control of layer thickness, stacking order, and
      crystallinity. To meet this goal, researchers need a comprehensive understanding
      and effective controlling of the growth process, especially to its elementary
      steps. In this Account, we focus on our recent progresses toward the controlled
      surface growth of graphene and its two-dimensional (2D) hybrids via rational
      designs of CVD elementary processes, namely, process engineering. A typical CVD
      process consists of four main elementary steps: (A) adsorption and catalytic
      decomposition of precursor gas, (B) diffusion and dissolution of decomposed
      carbon species into bulk metal, (C) segregation of dissolved carbon atoms onto
      the metal surface, and finally, (D) surface nucleation and growth of graphene.
      Absence or enhancement of each elementary step would lead to significant changes
      in the whole growth process. Metals with certain carbon solubility, such as
      nickel and cobalt, involve all four elementary steps in a typical CVD process,
      thus providing us an ideal system for process engineering. The elementary
      segregation process can be completely blocked if molybdenum is introduced into
      the system as an alloy catalyst, yielding perfect monolayer graphene almost
      independent of growth parameters. On the other hand, the segregation-only process
      of predissolved solid carbons is also capable of high-quality graphene growth. By
      using a synergetic Cu-Ni alloy, we are able to further enhance the control to
      such a segregation technique, especially for the thickness of graphene. By
      designing a cosegregation process of carbon atoms with other elements, such as
      nitrogen, doped graphene could be synthesized directly with a tunable doping
      profile. Copper with negligible carbon solubility provides another platform for
      process engineering, where both carbon dissolution and segregation steps are
      negligible in the CVD process. Carbon atoms decomposed from precursors diffuse on
      the surface and build up the thermodynamically stable honeycomb lattice. As a
      result, graphene growth on copper is self-limited, and formation of multilayer
      graphene is generally prohibited. Being able to control this process better, as
      well as the high quality produced, makes copper-based growth the dominating
      synthesis procedure in the graphene community. We designed a two-temperature zone
      system to spatially separate the catalytic decomposition step of carbon
      precursors and the surface graphitization step for breaking this self-limited
      growth feature, giving high-quality Bernal stacked bilayer graphene via van der
      Waals epitaxy. We performed the so-called wrinkle engineering by growing graphene
      on nanostructured copper foil together with a structure-preserved surface
      transfer. In such a way, we controlled the wrinkling or folding on graphene and
      further fabricated graphene nanoribbon arrays by self-masked plasma etching.
      Moreover, by designing a two-step patching growth process on copper, we succeeded
      in synthesizing the mosaic graphene, a patchwork of intrinsic and nitrogen-doped
      graphene connected by single crystalline graphene p-n junctions. By following a
      general concept of process engineering, our work on the designed CVD growth of
      graphene and its 2D hybrids provides a unique insight of this research field. It
      enables the precise growth control of graphene together with the in-depth
      understanding of CVD growth process, which would further stimulate the pace of
      graphene applications.

PMID- 23869402
TI  - Filtration recovery of extracellular DNA from environmental water samples.
AB  - qPCR methods are able to analyze DNA from microbes within hours of collecting
      water samples, providing the promptest notification and public awareness possible
      when unsafe pathogenic levels are reached. Health risk, however, may be
      overestimated by the presence of extracellular DNA (eDNA) that is corecovered by
      the filtration procedure which is the most commonly used method to concentrate
      target microbes from environmental waters. Using C. parvum 18S rRNA gene fragment
      as a representative of eDNA, we examined the impact of filters (types and pore
      sizes) and physiochemical properties of surface water samples on the recovery of
      spiked DNA. Our results indicated that binding affinities of various filter
      membranes were quantifiably different for eDNA fragments with the polycarbonate
      (PC) binding the least and mixed cellulose acetate and cellulose nitrate (MCE)
      binding the most as evidenced by up to 16% recovery of the spiked plasmid DNA
      with a pore size of 0.2 MUm. Water quality parameters also had a distinct
      influence on the recovery of eDNA which was enhanced by the presence of high
      total suspended solid (TSS) concentrations and reduced pH. At pH 5.5, with 150
      mg/L of clay, DNA recovery was increased to as much as 18%. By shielding the
      negative charge, thus increasing the interaction of DNA and colloids, the
      increase of Na(+) and Ca(2+) concentrations resulted in more DNA binding and
      consequently more recovery from environmental water samples. Therefore, in
      addition to analytical uncertainties, potential differences in qPCR data from
      filtered waters characterized with low pH and high TSS and ionic strength should
      be considered in pollution assessments. 

PMID- 23869403
TI  - C9orf72 repeat expansions are not detected in Chinese patients with familial ALS.

PMID- 23869404
TI  - Woronin bodies, their impact on stress resistance and virulence of the pathogenic
      mould Aspergillus fumigatus and their anchoring at the septal pore of filamentous
      Ascomycota.
AB  - Hyphae of filamentous Ascomycota consist of compartments that are connected via
      septal pores. To avoid a dramatic loss of cellular content after wounding, fungi
      developed mechanisms to occlude their septal pores. In most Pezizomycotina, so
      called Woronin bodies are anchored in proximity to the pore. This is a prominent
      example for precise spatial positioning of organelles, but so far the underlying
      molecular organization has remained largely unknown. Using the pathogenic mould
      Aspergillus fumigatus, we provide evidence that Woronin bodies are important for
      stress resistance and virulence. Furthermore the molecular machinery anchoring
      them at the septum is described. Namely, we have identified Lah as the tethering
      protein and provide evidence that the Woronin body protein HexA binds to the
      septal pore in a Lah-dependent manner. Moreover, we demonstrate that a striking
      poly-histidine motif targets HexA to the septal cell wall. Thus, the axis HexA
      Lah is an excellent candidate for the tether linking Woronin bodies to the
      septum. This model applies to A.fumigatus, but most likely also to the vast
      majority of the Pezizomycotina. Our findings shed light on the evolution of
      Woronin body anchoring and provide a basis for the development of novel
      strategies to combat fungal pathogens like A.fumigatus.

PMID- 23869406
TI  - The effect of screw head design on rod derotation in the correction of
      thoracolumbar spinal deformity: laboratory investigation.
AB  - OBJECT: The use of fixed-axis pedicle screws for correction of thoracolumbar
      deformity in adult surgery is demanding because of the challenge of assembling
      the bent rod to the screw in order to achieve curve correction. Polyaxial screw
      designs, providing increased degrees of freedom at the screw-rod interface, were
      reported to be insufficient in achieving correction of thoracic deformity in the
      axial plane. Using a multisegment bovine calf spine model, this study
      investigated the ability of a new uniplanar screw design to achieve derotation
      correction of the vertebrae and maintain a degree of correction comparable to
      that of fixed-axis and polyaxial screw designs. METHODS: Eighteen calf
      thoracolumbar spine segments from T-6 to L-1 (n = 6 per screw design) underwent
      bilateral facetectomies at the T9-11 levels and were instrumented bilaterally
      with pedicle screws and rods. To assess the efficacy of each screw design in
      imparting rotational correction, each instrumented level was tested under applied
      torsional moments designed to simulate the motion applied during derotation
      surgery. Once rotation was achieved, the whole spine was tested to assess the
      overall stiffness of the construct. RESULTS: The fixed-axis construct showed
      increased efficacy in imparting rotation compared with the uniplanar (115%
      increase, p > 0.05) and polyaxial (210% increase, p < 0.05) constructs. Uniplanar
      screws showed a 21% increase in torsional stiffness compared with the polyaxial
      screws, but this difference was not statistically significant. CONCLUSIONS: The
      design of screw heads plays a significant role in affecting the rotation of the
      vertebrae during the derotation procedure. Uniplanar screws may have the
      advantage of maintaining construct stiffness after derotation.

PMID- 23869407
TI  - National trends in pancreaticoduodenal trauma: interventions and outcomes.
AB  - OBJECTIVES: Pancreaticoduodenal trauma (PDT) is associated with substantial
      mortality and morbidity. In this study, contemporary trends were analysed using
      national data. METHODS: The Nationwide Inpatient Sample for 1998-2009 was queried
      for patients with PDT. Interventions including any operation (Any-Op) and
      pancreas-specific surgery (PSURG) were identified. Trends in treatment and
      outcomes were determined [complications, length of stay (LoS), mortality] for the
      Any-Op, PSURG and non-operative (Non-Op) groups. Analyses included chi-squared
      tests, Cochran-Armitage trend tests and logistic regression. RESULTS: A total of
      27 216 patients (nationally weighted) with PDT were identified. Over time, the
      frequency of PDT increased by 8.3%, whereas the proportion of patients submitted
      to PSURG declined (from 21.7% to 19.8%; P = 0.0004) and the percentage of
      patients submitted to non-operative management increased (from 56.7% to 59.1%; P
      = 0.01). In the Non-Op group, mortality decreased from 9.7% to 8.6% (P < 0.001);
      morbidity and LoS remained unchanged at ~40% and ~12 days, respectively. In the
      PSURG group, mortality remained stable at ~15%, complications increased from
      50.2% to 71.8% (P < 0.0001) and LoS remained stable at ~21 days. For all PDT
      patients, significant independent predictors of mortality included: the presence
      of combined pancreatic and duodenal injuries; penetrating trauma, and age >50
      years. Having any operation (Any-Op) was associated with mortality, but PSURG was
      not a predictor of death. CONCLUSIONS: The utilization of operations for PDT has
      declined without affecting mortality, but operative morbidity increased
      significantly over the 12 years to 2009. The development of an evidence-based
      approach to invasive manoeuvres and an early multidisciplinary approach involving
      pancreatic surgeons may improve outcomes in patients with these morbid injuries.

PMID- 23869408
TI  - Epidemiology and risk factors for chronic kidney disease in patients with
      ischaemic stroke.
AB  - BACKGROUND: There is growing evidence for an association between chronic renal
      disease (CKD) and adverse cerebrovascular events because of the overlap of
      several risk factors. The purpose of this study is to examine the epidemiology of
      CKD and the characteristics of risk factors for CKD in the population with
      ischaemic stroke. METHODS: This retrospective study included 571 patients with
      ischaemic stroke. Estimated glomerular filtration rate (eGFR) was calculated by
      the Modification of Diet in Renal Disease (MDRD) study equation. Renal function
      was assessed according to the Kidney Disease Outcomes Quality Initiative (K/DOQI)
      CKD classification. RESULTS: Study demonstrated that the major factors associated
      with CKD in the ischaemic stroke patients were age, diabetes mellitus,
      hypertension, systolic blood pressure, LDL cholesterol and serum uric acid.
      Diabetes mellitus (OR 4.146, 95% CI 1.047-16.418, P = 0.043), hypertension and
      diabetes mellitus (OR 3.574, 95% CI 1.248-10.234, P = 0.018), serum uric acid (OR
      1.010, 95% CI 1.006-1.013, P < 0.001) and LDL cholesterol (OR 1.431, 95% CI 1.063
      1.928, P = 0.018) were independent risk factors associated with CKD in the
      patients with ischaemic stroke. CONCLUSIONS: The patients with ischaemic stroke
      may be considered as a high-risk population for CKD and be aggressively managed
      for CKD prevention. The high prevalence of CKD in population with ischaemic
      stroke prompts the need for greater public awareness about risks of CKD.

PMID- 23869409
TI  - Training innate immunity: the changing concept of immunological memory in innate
      host defence.
AB  - The inability of innate immunity to build an immunological memory is considered a
      main difference with adaptive immunity. This concept has been challenged by
      studies in plants, invertebrates and mammals. Recently, a paradigm shift in our
      understanding host defence has been triggered by the mounting evidence for innate
      immune memory, leading to increased responses to secondary infections. Important
      differences between the cell populations and the molecular mechanisms exist
      between the adaptive traits of innate host defence on the one hand and
      immunological memory of adaptive immunity on the other hand. The lasting state of
      enhanced innate immunity termed 'trained immunity' is mediated by prototypical
      innate immune cells such as natural killer cells and monocytes/macrophages. It
      provides protection against reinfection in a T/B-cell-independent manner, with
      both specific mechanisms and nonspecific epigenetic reprogramming mediating these
      effects. This concept represents a paradigm change in immunity, and its putative
      role in resistance to reinfection may represent the next step in the design of
      future vaccines. 

PMID- 23869410
TI  - Keeping mitochondria in shape: a matter of life and death.
AB  - BACKGROUND: Mitochondria are dynamic organelles that participate in energy
      conversion, metabolism, signaling and apoptosis. To fulfill their multiple tasks,
      mitochondria come in varied morphologies and ultrastructures resulting from the
      equilibrium between fusion and fission, Furthermore, they are in close contact
      with the endoplasmic reticulum generating an essential interface in cell
      physiology and death. MATERIALS AND METHODS: In this review we will discuss the
      impact of our findings on the molecular mechanisms of mitochondrial morphology
      and tethering to the endoplasmic reticulum on cell death. RESULTS AND
      CONCLUSIONS: The work reviewed here supports a key role for mitochondrial
      dynamics in cell life and death and in disease.

PMID- 23869411
TI  - Melatonin ameliorates endothelial dysfunction, vascular inflammation, and
      systemic hypertension in rats with chronic intermittent hypoxia.
AB  - The pathogenesis of hypertension in patients with obstructive sleep apnea (OSA)
      is associated with endothelial dysfunction induced by chronic intermittent
      hypoxia (IH). Studies have shown that administration of melatonin ameliorates
      oxidative injury and inflammation. This study examined the effect of melatonin on
      the oxidative stress, endothelial dysfunction, and inflammation during the
      pathogenesis of hypertension in chronic IH. Adult Sprague-Dawley rats that had
      received a daily injection of melatonin or vehicle were exposed to IH treatment
      mimicking a severe OSA condition for 14-21 days. Systolic pressure was
      significantly higher in the vehicle-treated (144 +/- 2.7 mmHg) but not in the
      melatonin-treated rats (123 +/- 5.1 mmHg) by 21-day IH treatment when compared
      with the normoxic control. Levels of malondialdehyde and the expressions of NADPH
      oxidase, pro-inflammatory mediators (TNF-alpha, inducible NO synthase, COX-2),
      and adhesion molecules (ICAM-1, VCAM-1, and E-selectin) of the thoracic aorta
      were markedly increased by 14-day IH treatment preceding the hypertensive
      response. Also, levels of nitric oxide (NO), endothelial-dependent relaxation,
      and the expressions of endothelial NO synthase (eNOS) and antioxidant enzymes
      (GPx, CAT, and Cu/Zn SOD) were significantly lowered in the IH rats. Melatonin
      treatment significantly mitigated the increased expression of NADPH oxidase, pro
      inflammatory mediators, and adhesion molecules. Moreover, melatonin prevented the
      endothelial dysfunction with ameliorated levels of NO, endothelial-dependent
      relaxation, and expressions of eNOS and antioxidant enzymes. These results
      suggest that melatonin is protective against IH-induced hypertension and
      endothelial dysfunction via an antioxidant and anti-inflammatory mechanism. 

PMID- 23869412
TI  - Esophageal stenting for treatment of refractory benign esophageal strictures in
      dogs.
AB  - BACKGROUND: Benign esophageal strictures can recur despite multiple dilatation
      procedures and palliative management can be challenging. OBJECTIVE: To describe
      the technique and determine the outcome of esophageal stenting for treatment of
      refractory benign esophageal strictures (RBES) in dogs. ANIMALS: Nine dogs with
      RBES. METHODS: Retrospective review of records for dogs with RBES. Indwelling
      intraluminal esophageal stents were placed transorally with endoscopy,
      fluoroscopic guidance, or both. Follow-up information was obtained via medical
      record or telephone interview. RESULTS: Nine dogs had 10 stents placed including
      biodegradable stents (BDS) (6/10), self-expanding metallic stents (SEMS) (3/10),
      and a self-expanding plastic stent (SEPS) (1/10). All dogs had short-term
      improved dysphagia. Complications included ptyalism, apparent nausea, gagging,
      vomiting, or regurgitation (8/9), confirmed recurrence of stricture (6/9), stent
      migration (3/9), stent shortening (1/9), megaesophagus (1/9), incisional
      infection (1/9), and tracheal-esophageal fistula (1/9). Eight of 9 dogs required
      intervention because of the complications of which 4 of 8 dogs were eventually
      euthanized because of stent-related issues. One dog was lost to follow-up
      examination. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings suggest that
      esophageal stent placement was safe and technically effective, but unpredictably
      tolerated in dogs with RBES. If a stent is placed, dogs should be monitored
      carefully for stent migration, dissolution of absorbable stents, and recurrence
      of strictures.

PMID- 23869413
TI  - Characteristics and prognosis of Asian patients with type 2 diabetes from a multi
      racial Australian community: the Fremantle Diabetes Study.
AB  - BACKGROUND: Asian migrants represent an expanding proportion of the Australian
      population and are from a region with an increasing diabetes burden. There are
      few data detailing the characteristics and outcome of type 2 diabetes in Asian
      Australians. AIMS: To determine whether the phenotype and prognosis of Asians
      with type 2 diabetes differ from those in Anglo-Celt (AC) patients from the same
      Australian community. METHODS: We studied 44 Asian and 796 AC patients from the
      Fremantle Diabetes Study. Each had a detailed assessment between 1993 and 1996,
      and was invited to annual reviews for >=5 years. Data linkage provided additional
      endpoints to end-2010. Cox proportional hazards modelling was used to determine
      predictors of cardiovascular disease (CVD) death and all-cause mortality.
      RESULTS: The prevalence of type 2 diabetes in Asians and the general population
      in Fremantle was similar (1.5% vs 1.6%; P = 0.60). The Asian patients were
      younger, less obese and less likely to be hypertensive than the AC subjects, but
      they had a higher retinopathy prevalence (27.3% vs 13.5%; P = 0.023). During up
      to 18 years of follow up, 12 Asians and 428 AC patients died, 2 (16.7%) vs 205
      (47.9%) from CVD (P = 0.040). Asian ethnicity was independently protective
      against CVD death (hazard ratio 0.13 (95% confidence interval: 0.02-0.96); P =
      0.046) but not all-cause mortality (hazard ratio 0.58 ( 95% confidence interval:
      0.31-1.10); P = 0.10). CONCLUSIONS: The phenotype of type 2 diabetes in a
      relatively small group of well-characterised Asian Australians differed from that
      in AC patients from the same urban community. Their favourable cardiovascular
      prognosis may reflect a healthy migrant effect.

PMID- 23869414
TI  - Study of the behaviour of lesional and nonlesional skin of canine recurrent flank
      alopecia transplanted to athymic nude mice.
AB  - BACKGROUND: Recurrent flank alopecia is a clinically well-described skin disorder
      in dogs. The pathomechanism of the disease is difficult to study because it
      undergoes spontaneous regression. HYPOTHESIS/OBJECTIVES: To study the behaviour
      of xenografts in mice in order to assess the feasibility of a reproducible
      experimental model and to investigate local or systemic causes of canine
      recurrent flank alopecia (cRFA). METHODS: Skin biopsies were taken from lesional
      and nonlesional skin of two client-owned dogs with cRFA and grafted onto five
      athymic mice from a research facility. The lesional skin and xenografted skin
      were evaluated histologically on day 0 and day 30, respectively. RESULTS:
      Transplanted lesional and nonlesional canine skin regrew hair within 30 days,
      while the donor dogs were still alopecic in the lesional areas on day 30 after
      the skin biopsy procedure. Graft rejection was evidenced histologically in two
      xenografted athymic mice. Lesional hyperpigmentation disappeared in the athymic
      mice. CONCLUSIONS AND CLINICAL IMPORTANCE: This study showed that hair follicles
      from dogs with cRFA quickly regenerated and regrew hair once grafted onto the
      mice. Our data indicate that the pathogenesis of cRFA is likely to be mediated by
      systemic rather than local factors. While this xenograft approach might not be of
      much value for the study of cRFA, it has potential value for the study of other
      causes of canine alopecia due to systemic factors.

PMID- 23869415
TI  - Mid-long-term results after aortic arch repair using a four-branched graft with
      antegrade selective cerebral perfusion.
AB  - BACKGROUND AND AIM OF THE STUDY: The purpose of this study is to evaluate mid
      long-term results of aortic arch replacement. METHODS: Between 1992 and 2012, 263
      consecutive patients underwent aortic arch repair in our institution. Follow-up
      rate was 92%, and 243 patients were enrolled in this study. Two hundred twelve
      patients (87%) underwent total arch replacement using a four-branched graft with
      antegrade selective cerebral perfusion. Ninety-nine patients (41%) were operated
      on for acute aortic dissection. RESULTS: Hospital mortality was 13.2%. The mean
      follow-up duration was 3.6 +/- 3.7 (0-19) years. Late mortality occurred in 38
      patients, 4.3 +/- 3.2 (0.3-14.1) years after surgery. The survival rates were
      85%, 70%, and 50% at one, five, and 10 years. In the acute type A aortic
      dissection group, survival rate at one and five years was 86% and 79%. In the
      nonacute type A dissection group, one- and five-year survivals were 85% and 62%
      (log-rank test: p=0.0027). The causes of late mortality were respiratory failure
      in five, aortic aneurysm rupture in six, cancer in four, stroke in eight, others
      in seven, and unknown in eight. Twenty-six patients had another aortic
      intervention 3.6 +/- 6.0 (0.04-19.6) years after arch repair. Seven patients had
      stroke after discharge 6.5 +/- 3.9 (1.9-13.0) years after repair. CONCLUSIONS:
      Mid-long-term results after aortic arch repair with antegrade selective cerebral
      perfusion were satisfactory. Acute type A aortic dissection did not negatively
      influence the mid-long-term survival.

PMID- 23869417
TI  - Impact of Helicobacter pylori infection on normal colorectal mucosa, adenomatous
      polyps and adenocarcinoma sequence.

PMID- 23869416
TI  - Mapping attitudes and awareness with regard to national guidelines: an e-mail
      survey among decision makers.
AB  - INTRODUCTION: The adoption of evidence-based guidelines within the mental health
      field has been slow. Changing inadequate practice is therefore a formidable
      challenge for mental health-care managers. AIM: To explore decision-makers'
      attitudes and awareness regarding the national guidelines for psychosocial
      interventions targeting people with schizophrenia. METHOD: A questionnaire
      distributed by e-mail to 592 Swedish decision-makers was analysed using
      descriptive and comparative techniques. RESULTS: Significantly more of the top
      level mental health-care managers than politicians stated that they knew about
      the national guidelines (i.e. their release and content) and they considered the
      guidelines to be a good source of support for planning and allocating resources.
      CONCLUSION: If those responsible for allocating resources (i.e. politicians) are
      unaware of the dissemination of national guidelines or their content, and they do
      not perceive the national guidelines to be a good source of support for planning
      and allocating resources, this is likely to have a negative influence on the
      remit of nurse managers as well as nursing practice. IMPLICATIONS FOR NURSING
      MANAGEMENT: Top-level mental health-care managers have a vital role to play in
      the implementation of national guidelines. However, our findings indicate that
      implementing national guidelines in practice could be virtually impossible
      without strategic government support.

PMID- 23869418
TI  - Association between a 11beta-hydroxysteroid dehydrogenase type 1 gene
      polymorphism and metabolic syndrome in a South Indian population.
AB  - INTRODUCTION: The striking phenotypic similarities between metabolic syndrome and
      the Cushing syndrome of glucocorticoid excess have often been linked to 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which activates inert
      precursors like the cortisone, 11-dehydrocortisone to active glucocorticoids by
      oxo-reductase activity in several organs. Thus, increased expression of 11beta
      HSD1 is associated with insulin resistance, diabetes, hypertension, and
      dyslipidemia. In this study, we investigated the association of a common
      polymorphism of the HSD11B1 gene with metabolic syndrome and its components.
      MATERIALS AND METHODS: The study included 205 subjects, including 105 diagnosed
      with metabolic syndrome and 100 controls. The subjects were genotyped for the
      HSD11B1 gene polymorphism (rs12086634) T->G using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). The distribution of the
      genotypes and its association with clinical and biochemical parameters were
      assessed. RESULTS: There was a significant association between the HSD11B1 gene
      polymorphism (rs12086634) and occurrence of metabolic syndrome compared to
      controls (P<0.0001). Regarding the rs1206634 T->G variant, heterozygous patients
      had a higher systolic blood pressure (P=0.039), higher prevalence of diabetes
      (P=0.010), and higher total cholesterol levels (P=0.006) compared to homozygotes.
      However, there was no significant association of the polymorphism with obesity or
      specific body habitus. CONCLUSION: We conclude that in a South Indian population,
      a polymorphism of the HSD11B1 gene containing the single-nucleotide polymorphism
      (SNP) rs12086634 T->G confers increased risk of metabolic syndrome.

PMID- 23869419
TI  - Medical management for adults with Prader-Willi syndrome.
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by
      morbid obesity resulting from insatiable appetite. Complications like diabetes
      mellitus or other cardiovascular diseases typically occur during lifetime.
      Lifestyle advice and education as well as limited caloric intake are the major
      concepts in assistance of PWS patients. METHODS: A 12.9-month follow-up study,
      which included 8 formerly genetically diagnosed PWS patients, was conducted.
      Physical and laboratory examinations were done at the beginning and at the end of
      the follow-up. Improved medical care and lifestyle advice were given. The
      participants lived in an assisted living environment with a fixed daily schedule
      and limited caloric intake. RESULTS: The group of patients consisted of manifest
      diabetics (n=6) as well as nondiabetics (n=2). Therapeutic concepts were
      simplified in 2 patients by switching from insulin to oral antidiabetics. The
      reduction in body weight was moderate, but attributable to a loss of fat mass. A
      significant reduction in blood cholesterol and triglyceride content was achieved
      along the observational period as well as a significant reduction of glycosylated
      hemoglobin (HbA1c) in the group of diabetic PWS patients. Systolic blood pressure
      improved during the study. CONCLUSION: A combination of an assisted living
      environment following conservative treatments as well as consistent patient care
      improved the daily and medical situation of PWS patients. Weight loss and, as a
      consequence, improvements in terms of metabolic condition and blood pressure were
      observed. A combination of medical and daily routine management should be
      established in PWS patients to improve their quality of life.

PMID- 23869420
TI  - Desmoplastic melanoma presenting with localized hair repigmentation.

PMID- 23869421
TI  - Atrazine and Methyl Viologen Effects on Chlorophyll-a Fluorescence Revisited
      Implications in Photosystems Emission and Ecotoxicity Assessment.
AB  - In this work, we use the effect of herbicides that affect the photosynthetic
      chain at defined sites in the photosynthetic reaction steps to derive information
      about the fluorescence emission of photosystems. The interpretation of spectral
      data from treated and control plants, after correction for light reabsorption
      processes, allowed us to elucidate current controversies in the subject. Results
      were compatible with the fact that a nonnegligible Photosystem I contribution to
      chlorophyll fluorescence in plants at room temperature does exist. In another
      aspect, variable and nonvariable chlorophyll fluorescence were comparatively
      tested as bioindicators for detection of both herbicides in aquatic environment.
      Both methodologies were appropriate tools for this purpose. However, they showed
      better sensitivity for pollutants disconnecting Photosystem II-Photosystem I by
      blocking the electron transport between them as Atrazine. Specifically, changes
      in the (experimental and corrected by light reabsorption) red to far red
      fluorescence ratio, in the maximum photochemical quantum yield and in the quantum
      efficiency of Photosytem II for increasing concentrations of herbicides have been
      measured and compared. The most sensitive bioindicator for both herbicides was
      the quantum efficiency of Photosystem II.

PMID- 23869422
TI  - Asymmetric free-standing 2-D photonic crystal films and their Janus particles.
AB  - We report the fabrication of large area, thin asymmetric free-standing two
      dimensional (2-D) photonic crystals. We fabricate large area 2-D close-packed
      monodisperse polystyrene (PS) particle monolayers at air/water interfaces by
      using our needle tip flow method. We then layer tetraethyl orthosilicate (TEOS)
      onto the 2-D array to form a thin TEOS layer on the 2-D particle array on water.
      The hemispheres of PS particles located within the TEOS phase swell such that the
      adjacent particle hemispheres fuse. After TEOS evaporation, we obtain a free
      standing connected photonic crystal film of hemispheres that efficiently
      diffracts light. The other side of the photonic crystal film consists of a fused
      connecting thin, flat sheet. Reactive ion etching (RIE) of the asymmetric films
      forms unusual, rough particle 2-D arrays and 2-D flower-like arrays. Mechanical
      abrasion allows one to separate the resulting novel Janus particles. 

PMID- 23869423
TI  - Concomitant percutaneous coronary intervention and transcatheter aortic valve
      replacement: safe and feasible replacement alternative approaches in high-risk
      patients with severe aortic stenosis and coronary artery disease.
AB  - OBJECTIVE: Transcatheter aortic valve replacement (TAVR) is performed as a stand
      alone procedure in patients that are not suitable for surgical aortic valve
      replacement. However, a significant proportion of patients with severe aortic
      stenosis have coexisting coronary artery disease (CAD). We report concomitant
      TAVR and percutaneous coronary intervention (PCI) as a single procedure in such
      patients. METHODS: Three patients with severe aortic stenosis and CAD that were
      high risk for conventional surgery had concomitant alternative approach TAVR and
      PCI performed. Two patients had PCI and stent placement immediately after the
      deployment of the transapical transcatheter aortic valve, and one patient had a
      coronary artery stent placed just prior to the deployment of the transaortic
      transcatheter aortic valve. RESULTS: Two male patients and one female (age range
      68-91 years) had 100% procedural success with resolution of symptoms and zero
      residual stenosis. There were no complications related to neurologic events,
      worsening renal function, or myocardial infarction. In-hospital and 30-day
      mortality was zero. All three patients were discharged home with a median
      hospital stay of eight days. CONCLUSIONS: In our small series of patients
      presented we demonstrate that PCI and TAVR performed concurrently in the hybrid
      operating room is a feasible option in patients undergoing TAVR with coexisting
      CAD. Furthermore, we propose this single-stage approach in such high-risk
      patients as it decreases the number of procedures performed and may theoretically
      lower cost and hospital stay.

PMID- 23869424
TI  - Limonoid constituents of Euodia rutaecarpa var. bodinieri and their inhibition on
      NO production in lipopolysaccharide-activated RAW264.7 macrophages.
AB  - A new limonoid compound, named evorubodinin (1), was isolated from the dried and
      nearly ripe fruits of Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode)
      Huang (family Rutaceae), together with two known limonoid compounds, limonin (2)
      and evolimorutanin (3). The chemical structure of 1 was elucidated by
      spectroscopic method and single-crystal X-ray diffraction. The inhibitory effects
      of the isolated compounds 1-3 and the structurally related compounds evodol (4),
      shihulimonin A1 (5), evodirutaenin (6), 12alpha-hydroxyrutaevin (7), and rutaevin
      (8) on nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7
      macrophages were also assayed. All compounds 1-8 showed the inhibitory activity,
      in which both 7 and 8 with the uncommon 5beta-H configuration more efficiently
      inhibited NO production. The results provided valuable information for further
      investigation of compounds 1-8 as anti-inflammatory agents or lead compounds. 

PMID- 23869425
TI  - Comparison of the lactate minimum speed and the maximal lactate steady state to
      determine aerobic capacity in purebred Arabian horses.
AB  - AIM: To compare five different protocols for estimating the lactate minimum speed
      (LMS) with that for estimating the maximal lactate steady state (MLSS) in Arabian
      horses, in order to obtain a more rapid method for monitoring aerobic capacity
      and prescribing training schedules. METHODS: Eight purebred Arabian horses were
      conditioned to exercise on a treadmill for 12 days then submitted to three to
      five exercise sessions to determine the MLSS. Blood samples were collected from a
      jugular catheter at specific intervals for measurement of lactate concentrations.
      The MLSS was the velocity maintained during the last 20 minutes of constant
      submaximal exercise, at which the concentration of lactate increased by no more
      than 1.0 mmol/L. The LMS test protocols (P1 - P5) included a warm-up period
      followed by a high-intensity gallop. The speed was then reduced to 4 m/s, and the
      incremental portion of the test was initiated. In P1, P2, and P3, the velocity
      increment was 0.5 m/s, and the duration of each incremental stage was three, five
      and seven minutes, respectively. In P4 and P5, the velocity increments were 1.0
      and 1.5 m/s, respectively, and the duration of the stages was fixed at five
      minutes each. A second-degree polynomial function was fitted to the lactate
      velocity curve, and the velocity corresponding to the lowest concentration of
      lactate was the LMS. RESULTS: Only the mean LMS determined by P1 and P2 did not
      differ from the velocity determined by the MLSS test (p > 0.1). There was a
      strong correlation (r >0.6) between P1 and the MLSS velocity. A limits of
      agreement plot revealed that the best agreement occurred between the MLSS test
      and P1 (mean bias = 0.14 m/s), followed by P2 (bias = -0.22 m/s). The lactate
      concentrations associated with the various LMS protocols did not differ.
      CONCLUSIONS: This study shows the variation between protocols of the LMS test for
      determining the onset of blood lactate accumulation but also reveals that, at
      least for Arabian horses, the P1 protocol of the LMS has good agreement with the
      MLSS.

PMID- 23869426
TI  - Mometasone furoate hydrogel for scalp use: in vitro and in vivo evaluation.
AB  - Dermatological inflammatory diseases often affect the scalp and the eyebrows.
      Common dosage forms available on the market for those situations are lotions;
      however, the presence of hair limits their use. Gels, for their consistency and
      adhesiveness, are a suitable alternative to the lotions in these situations. The
      aim of this study was to develop a new stable gel containing mometasone furoate
      (MF), with anti-inflammatory activity and a controlled delivery, to improve
      topical treatment of scalp dermatitis. Pharmaceutical development, physical and
      chemical characterization, stability, in vitro release and permeation studies and
      in vivo anti-inflammatory activity were performed. The gel presented an acidic pH
      and an apparent viscosity of 35 Pa.s. The microbiological analysis showed that
      the results were within the established specification limits. The release and the
      permeation profiles suggest that the drug is mainly retained in the upper skin
      layers. MF gel was tested in an animal model of cutaneous inflammation and
      presented similar anti-inflammatory activity compared to a commercially available
      MF dosage form. The gel was chemically, physically and microbiologically stable.
      The results suggest that the developed hydrogel formulation containing MF can be
      of actual value for improving the clinical effectiveness in the treatment of
      scalp dermatitis.

PMID- 23869427
TI  - Surgery for a large obstructive pelvic tumour associated with neurofibromatosis.

PMID- 23869428
TI  - The use of sublingual fentanyl for breakthrough pain by using doses proportional
      to opioid basal regimen.
AB  - OBJECTIVE: The aim of this study was to prospectively assess the efficacy and
      safety of sublingual fentanyl (SLF) in doses proportional to opioid doses used
      for background analgesia for the treatment of BTP of cancer patients. METHODS: A
      sample of patients admitted to an acute palliative care unit, presenting
      breakthrough pain (BTP) episodes and receiving stable doses of opioids for
      background pain was selected to assess the efficacy and safety of SLF used in
      doses proportional to the basal opioid regimen used for the management of BTP.
      For each patient, data from four consecutive episodes were collected. For each
      episode, nurses collected changes in pain intensity and adverse effects when pain
      got severe (T0), and 5, 10, and 15 minutes after SLF was given (T15). RESULTS:
      Seventy patients were recruited for the study. The mean age was 61.7 (+/-11.5).
      Forty-one patients were males. A total of 173 episodes of BTP were recorded (mean
      2.5 episodes/patient). In 19 events, documentation regarding changes in pain
      intensity was incomplete. Of the 154 evaluable episodes, 143 were successfully
      treated (92%). Mean doses of SLF were 637 ug (SD 786), and 51 patients (72.8%)
      received SLF doses >=800 ug. When compared to younger adult patients, older
      patients received significantly lower doses of SLF (p < 0.0005) [DOSAGE ERROR
      CORRECTED], similarly to their lower basal opioid regimen. Pain intensity
      significantly decreased at T5, 10 and T15 (p < 0.0005). The number of patients
      with a pain reduction of more than 33% at T5, T10, and T15 were 11, 79, and 137,
      respectively, and the number of patients with a reduction in pain intensity of
      more than 50% were 1, 21, 114 at the same intervals, respectively. No differences
      in changes in pain intensity for gender (p < 0.9) or age (p < 0.85) were
      observed. No significant changes in the number of patients reporting adverse
      effects of mild-moderate intensity were reported after SLF administration in
      comparison with baseline, and no adverse effects severe enough in intensity to
      require medical intervention were observed. Limitations of this study are
      represented by the uncontrolled design. CONCLUSION: This study suggests that SLF
      given in doses proportional to the basal opioid regimen for the management of BTP
      is safe and effective in clinical practice.

PMID- 23869429
TI  - Melatonin inhibits visfatin-induced inducible nitric oxide synthase expression
      and nitric oxide production in macrophages.
AB  - Aberrant expression of inducible nitric oxide synthase (iNOS) in macrophages,
      which has been reported to be suppressed by melatonin, has an important
      contribution in the development of pathological inflammation. Visfatin, an
      adipokine, regulates the expression of various inflammatory factors, leading to
      inflammation; however, the influence of visfatin on iNOS-driven processes in
      macrophages is unclear. Here, we report the assessment of the role of visfatin in
      the regulation of iNOS gene expression in macrophages. Our data show that the
      levels of iNOS protein in peritoneal macrophages as well as nitric oxide (NO) in
      blood plasma were significantly lower after lipopolysaccharide treatment in
      visfatin(+/-) mice than those in the WT mice. In addition, visfatin increases
      iNOS mRNA and protein levels in RAW 264.7 cells, along with increasing production
      of NO. The enhancement of iNOS expression was prevented by treating the cells
      with inhibitors of the Janus kinase 2/signal transducers and activators of
      transcription 3 (JAK2/STAT3), nuclear factor (NF)-kappaB, extracellular signal
      regulated kinase 1/2, and c-Jun N-terminal kinase pathways. Our results also show
      that visfatin-induced iNOS expression and NO production were significantly
      inhibited by melatonin, an effect that was closely associated with a reduction in
      phosphorylated JAK2/STAT3 levels and with the inhibition of p65 translocation
      into nucleus. In conclusion, our data show, for the first time, that melatonin
      suppresses visfatin-induced iNOS upregulation in macrophages by inhibiting the
      STAT3 and NF-kappaB pathways. Moreover, our data suggest that melatonin could be
      therapeutically useful for attenuating the development of visfatin-iNOS axis
      associated diseases. 

PMID- 23869430
TI  - Whole-genome comparison of meticillin-resistant Staphylococcus aureus CC22
      SCCmecIV from people and their in-contact pets.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) infections remain
      important medical and veterinary challenges. The MRSA isolated from dogs and cats
      typically belong to dominant hospital-associated clones, in the UK mostly EMRSA
      15 (CC22 SCCmecIV), suggesting original human-to-animal transmission.
      Nevertheless, little is known about host-specific genetic variation within the
      same S. aureus lineage. HYPOTHESIS/OBJECTIVES: To identify host-specific
      variation amongst MRSA CC22 SCCmecIV by comparing isolates from pets with those
      from in-contact humans using whole-genome microarray. METHODS: Six pairs of MRSA
      CC22 SCCmecIV from human carriers (owners and veterinary staff) and their
      respective infected in-contact pets were compared using a 62-strain whole-genome
      S. aureus microarray (SAM-62). The presence of putative host-specific genes was
      subsequently determined in a larger number of human (n = 47) and pet isolates (n
      = 93) by PCR screening. RESULTS: Variation in mobile genetic elements (MGEs)
      occurred frequently and appeared largely independent of host and in-contact pair.
      A plasmid (SAP078A) encoding heavy-metal resistance genes (arsR, arsA, cadA,
      cadC, mco and copB) was found in three of six human and none of six animal
      isolates. However, only two of four resistance genes were associated with human
      hosts (P = 0.015 for arsA and cadA). CONCLUSIONS AND CLINICAL IMPORTANCE: The
      variation found amongst MGEs highlights that genetic adaptation in MRSA
      continues. However, host-specific MGEs were not detected, which supports the
      hypothesis that pets may not be natural hosts of MRSA CC22 and emphasizes that
      rigorous hygiene measures are critical to prevent contamination and infection of
      dogs and cats. The host specificity of individual heavy-metal resistance genes
      warrants further investigation into different selection pressures in humans and
      animals.

PMID- 23869431
TI  - Exploring medical student decisions regarding attending live lectures and using
      recorded lectures.
AB  - BACKGROUND: Student decisions about lecture attendance are based on anticipated
      effect on learning. Factors involved in decision-making, the use of recorded
      lectures and their effect on lecture attendance, all warrant investigation. AIM:
      This study was designed to identify factors in student decisions to attend live
      lectures, ways in which students use recorded lectures, and if their use affects
      live lecture attendance. METHODS: A total of 213 first (M1) and second year (M2)
      medical students completed a survey about lecture attendance, and rated factors
      related to decisions to attend live lectures and to utilize recorded lectures.
      Responses were analyzed overall and by class year and gender. RESULTS: M1
      attended a higher percentage of live lectures than M2, while both classes used
      the same percentage of recorded lectures. Females attended more live lectures,
      and used a smaller percentage of recorded lectures. The lecturer was a key in
      attendance decisions. Also considered were the subject and availability of other
      learning materials. Students use recorded lectures as replacement for live
      lectures and as supplement to them. CONCLUSIONS: Lectures, both live and
      recorded, are important for student learning. Decisions about lecture placement
      in the curriculum need to be based on course content and lecturer quality.

PMID- 23869433
TI  - Cardiac considerations in the operative management of the patient with Duchenne
      or Becker muscular dystrophy.
AB  - Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) is a progressive
      multisystem neuromuscular disorder. In addition to the skeletal muscle, the
      myocardium in the DMD/BMD patient is dystrophin deficient which results in a
      progressive cardiomyopathy. The myopathic myocardium poses significant risk of
      increased morbidity and mortality at the time of major surgical procedures.
      Careful attention must be given to the DMD/BMD patient during the intraoperative
      and postoperative period. Anesthesia selection is critical and anesthetics should
      be avoided which have been shown to be harmful in this patient population.
      Preanesthesia assessment should include cardiac consultation and detailed
      preoperative evaluation. Intraoperative management needs to insure that the
      weakened myocardium is not compromised by physiologic changes such as hypotension
      or major fluid shifts. Finally, attention to the cardiac status of the patient
      must continue into the postoperative period. The surgical care of the DMD/BMD
      patient requires a multispecialty approach to insure operative success. 

PMID- 23869434
TI  - Water loss control using pressure management: life-cycle energy and air emission
      effects.
AB  - Pressure management is one cost-effective and efficient strategy for controlling
      water distribution losses. This paper evaluates the life-cycle energy use and
      emissions for pressure management zones in Philadelphia, Pennsylvania, and
      Halifax, Nova Scotia. It compares water savings using fixed-outlet and flow
      modulated pressure control to performance without pressure control, considering
      the embedded electricity and chemical consumption in the lost water, manufacture
      of pipe and fittings to repair breaks caused by excess pressure, and pressure
      management. The resulting energy and emissions savings are significant. The
      Philadelphia and Halifax utilities both avoid approximately 130 million liters in
      water losses annually using flow-modulated pressure management. The conserved
      energy was 780 GJ and 1900 GJ while avoided greenhouse gas emissions were 50 Mg
      and 170 Mg a year by Philadelphia and Halifax, respectively. The life-cycle
      financial and environmental performance of pressure management systems compares
      favorably to the traditional demand management strategy of installing low-flow
      toilets. The energy savings may also translate to cost-effective greenhouse gas
      emission reductions depending on the energy mix used, an important advantage in
      areas where water and energy are constrained and/or expensive and greenhouse gas
      emissions are regulated as in California, for example. 

PMID- 23869432
TI  - Perceived stress and mortality in a Taiwanese older adult population.
AB  - Perceived stress is associated with poor health outcomes including negative
      affect, increased susceptibility to the common cold and cardiovascular disease;
      the consequences of perceived stress for mortality, however, have received less
      attention. This study characterizes the relationship between perceived stress and
      11-year mortality in a population of Taiwanese adults aged 53+ years. Using the
      Survey of Health and Living Status of the Near Elderly and Elderly of Taiwan, we
      calculated a composite measure of perceived stress based on six items pertaining
      to the health, financial situation, and occupation of the respondents and their
      families. Proportional hazard models were used to determine whether perceived
      stress predicted mortality. After adjusting for sociodemographic factors only, we
      found that a one standard deviation increase in perceived stress was associated
      with a 19% increase in all-cause mortality risk during the 11-year follow-up
      period (hazard ratio, HR = 1.19, 95% confidence interval, CI 1.13-1.26). The
      relationship was greatly attenuated when perceptions of stress regarding health
      were excluded, and was not significant after adjusting for medical conditions,
      mobility limitations and depressive symptoms. We conclude that the association
      between perceived stress and mortality is explained by an individual's current
      health; however, our data do not allow us to distinguish between two possible
      interpretations of this conclusion: (a) the relationship between perceived stress
      and mortality is spurious, or (b) poor health acts as the mediator.

PMID- 23869435
TI  - TOBY play-pad application to teach children with ASD - A pilot trial.
AB  - PURPOSE: To investigate use patterns and learning outcomes associated with the
      use of Therapy Outcomes By You (TOBY. Playpad, an early intervention iPad
      application. METHODS: Participants were 33 families with a child with an autism
      spectrum disorder (ASD) aged 16 years or less, and with a diagnosis of autism or
      pervasive developmental disorder - not otherwise specified, and no secondary
      diagnoses. Families were provided with TOBY and asked to use it for 4-6 weeks,
      without further prompting or coaching. Dependent variables included participant
      use patterns and initial indicators of child progress. RESULTS: Twenty-three
      participants engaged extensively with TOBY, being exposed to at least 100
      complete learn units and completing between 17% and 100% of the curriculum.
      CONCLUSIONS: TOBY may make a useful contribution to early intervention
      programming for children with ASD delivering high rates of appropriate learning
      opportunities. Further research evaluating the efficacy of TOBY in relation to
      independent indicators of functioning is warranted.

PMID- 23869436
TI  - Hepatitis D virus in Victoria 2000-2009.
AB  - BACKGROUND: Hepatitis D virus (HDV) coinfection can adversely affect prognosis
      and complicate management of chronic hepatitis B. The epidemiology and clinical
      practices surrounding HDV in Australia are poorly understood, with no robust
      estimates of the burden of disease, and the extent of appropriate testing and
      clinical follow up is unknown. AIMS: To determine the number of reported cases of
      HDV in Victoria, Australia between 2000-2009 and to explore screening practices
      in patients at risk of HDV infection over the same time period. METHODS: Data
      regarding HDV diagnoses in Victoria for 2000-2009 were obtained from notifiable
      disease surveillance and public health laboratory testing records. Notifications
      data were analysed to determine risk factors and demographics of HDV diagnoses
      where available, and laboratory records used to determine screening practices and
      follow up testing. RESULTS: Eighty-seven notifications for HDV were recorded
      between 2000 and 2009. The median age at diagnosis was 34 (interquartile range 27
      44), and the majority of cases were men (77%) and born overseas (71.4% of those
      with country of birth reported). During the same period, 2314 Victorian residents
      were tested for HDV infection, with 110 (4.75%) found to be positive. Both the
      number of people testing positive and the number of tests conducted steadily
      increased between 2005 and 2009. Of those patients with positive HDV antibody
      results, less than half (44 patients, 40%) were subsequently evaluated for
      replicative infection by polymerase chain reaction. CONCLUSION: The number of
      people being tested for HDV has increased over the past decade; however, gaps in
      the appropriate follow-up of infected patients are apparent. Birth overseas has
      become an increasingly important risk factor in Victorian notifications,
      highlighting the need for routine testing of people living with chronic hepatitis
      B for HDV infection.

PMID- 23869437
TI  - Job satisfaction of Slovenian hospital nursing workforce.
AB  - AIM: To test the psychometric properties of the McCloskey-Mueller Satisfaction
      Scale and to assess which of the McCloskey-Mueller Satisfaction Scale
      dimensionalities have a considerable impact on job satisfaction of nursing
      employees in three public Slovenian hospitals. BACKGROUND: Job satisfaction of
      nurses is linked to productivity, turnover, absenteeism and patient outcomes.
      Little is known about the factors contributing to job satisfaction among
      Slovenian hospital nurses. Understanding the contributing factors could help
      nurse managers to take appropriate measures. METHOD: A cross-sectional survey
      study was used to obtain a sample of 169 registered nursing assistants and 74
      registered nurses working in three public hospitals in Slovenia, from which data
      was obtained using the McCloskey-Mueller Satisfaction Scale. Dimensionality was
      tested using exploratory factor analysis. RESULTS: A seven-factor structure of 29
      items was obtained, which accounted for 54.3% of the total variance in job
      satisfaction, and was internally consistent (Cronbach's alpha coefficient of the
      instrument was 0.78). The first factor 'Satisfaction with Interaction
      Opportunities', which is a component of the social rewards dimension in the
      McCloskey-Mueller Satisfaction Scale, explained 30.6% of the variation.
      CONCLUSION: The registered nursing assistants' job dissatisfaction was higher
      than that of the registered nurses. Both were mostly dissatisfied with
      professional opportunities. Using the factor analysis, a seven-factor structure
      was found instead of the originally introduced eight-factor model, which suggests
      a need for further redevelopment of the McCloskey-Mueller Satisfaction Scale.
      IMPLICATIONS FOR NURSING MANAGEMENT: The results suggest that operational
      management needs to revitalize the work environment by ensuring proactive
      leadership and allowing participation in the decision-making process, while
      health-care organisations need to support the professional development of
      registered nursing assistants and registered nurses in order to achieve
      sustainable effects in job satisfaction.

PMID- 23869438
TI  - Evaluation of hair cortisol in the diagnosis of hypercortisolism in dogs.
AB  - BACKGROUND: Measurement of hair cortisol is a noninvasive technique used for
      several purposes in humans and in animals. OBJECTIVES: To measure hair cortisol
      concentrations (HCC) in dogs with spontaneous hypercortisolism (HC) and determine
      whether it can represent a useful diagnostic test for this syndrome. ANIMALS:
      Twenty-two dogs with spontaneous HC before treatment, 28 sick control dogs (SCD),
      and 40 healthy dogs. METHODS: In this prospective, observational clinical study,
      the HCC was measured by an RIA assay after extraction in HC dogs, in dogs with
      other chronic diseases, and in healthy dogs. The diagnostic accuracy of HCC was
      evaluated by subjecting data from dogs with HC and dogs with other chronic
      diseases to receiver operating characteristic (ROC) curve analysis. RESULTS:
      Median (range) cortisol concentration in dogs with HC was 4.53 pg/mg (0.32-74.62
      pg/mg) and was significantly higher than in SCD (1.49 pg/mg, 0.13-14.19 pg/mg)
      and healthy dogs (1.28 pg/mg, 0.34-5.38 pg/mg). Within the 3 groups, there was a
      large overlap of HCC. The area under the ROC curve was 0.80 (95% CI: 0.67-0.92).
      A cut-off value of HCC of 1.93 pg/mg revealed 91% sensitivity and 61% specificity
      to diagnose HC. CONCLUSIONS AND CLINICAL IMPORTANCE: Hair cortisol concentrations
      are higher in dogs with HC compared to SCD and healthy dogs. It is a noninvasive
      technique that should be further investigated as a possible diagnostic procedure
      for the diagnosis of HC in dogs.

PMID- 23869439
TI  - A comparison of right posterior sectorectomy with formal right hepatectomy: a
      dual-institution study.
AB  - OBJECTIVES: Right posterior sectorectomy (RPS) preserves liver volume but
      typically requires a longer parenchymal transection distance than does right
      hepatectomy (RH). This study was conducted to define the advantages of one
      approach over the other. METHODS: Databases at two institutions were
      retrospectively reviewed for all patients submitted to RPS or RH between January
      2000 and August 2012. Primary outcomes were perioperative complications and 90
      day mortality. RESULTS: Patients undergoing RPS (n = 100) and RH (n = 480),
      respectively, were similar in demographics, comorbidities, operative indications
      and Model for End-stage Liver Disease (MELD) mean scores (7.8 in the RPS group
      and 7.7 in the RH group; P = 0.49). A comparison of the RPS group with the RH
      group showed no significant differences in mean estimated blood loss (697 ml
      versus 713 ml; P = 0.900), rate of transfusions (19.2% versus 17.1%; P = 0.720),
      margin-positive resection (9.2% versus 11.6%; P = 0.70), complications (41.8%
      versus 42.0%; P = 1.000), bile leak (3.0% versus 4.0%; P = 1.000), or length of
      stay (7.5 days versus 8.3 days; P = 0.360). Postoperative hepatic insufficiency
      (defined as a postoperative bilirubin level of >7 mg/dl or significant ascites),
      occurred less frequently after RPS (1.0% versus 8.5%; P = 0.005). Operation type
      remained an independent determinant of postoperative hepatic insufficiency after
      controlling for preoperative risk factors (RH: hazard ratio = 9.628, 95%
      confidence interval 1.295-71.573; P = 0.027). A total of 28 (4.8%) patients died
      within 90 days; these included 25 (5.2%) patients in the RH group and three
      (3.0%) in the RPS group (P = 0.449). CONCLUSIONS: Despite similar blood loss and
      overall morbidity, RPS is associated with less hepatic insufficiency than RH.
      Right posterior sectorectomy is parenchyma-sparing and should be strongly
      considered when it is technically feasible and oncologically sound.

PMID- 23869440
TI  - Evaluating efficacy of bacteriophage therapy against Staphylococcus aureus
      infections using a silkworm larval infection model.
AB  - Silkworm larva has recently been recognized as an alternative model animal for
      higher mammals to evaluate the effects of antibiotics. In this study, we examined
      the efficacy of the bacteriophage (phage) therapy, which harnesses phages as
      antibacterial agents, against Staphylococcus aureus infections, using the
      silkworm larval infection model. Two newly isolated staphylococcal phages, S25-3
      and S13', were used as therapeutic phage candidates. They were assigned to two
      different lytic phage genera, Twort-like and AHJD-like viruses, based on their
      morphologies and the N-terminal amino acid sequences of the major capsid
      proteins. Both had a broad host range and strong lytic activity and showed
      preservative quality. Administration of these phages alone caused no adverse
      effects in the silkworm larvae. Moreover, the viruses showed life-prolonging
      effects in the silkworm larval infection model 10 min, 6 h, 12 h, and 24 h
      following infection. Such phage effects in the silkworm larval model were almost
      paralleled to the therapeutic efficacies in mouse models. These results suggest
      that phages S25-3 and S13' are eligible as therapeutic candidates and that the
      silkworm larval model is valid for the evaluation of phage therapy as well as
      mouse models. 

PMID- 23869441
TI  - Giant left atrial sarcoma.

PMID- 23869442
TI  - Enantioconvergent cross-couplings of racemic alkylmetal reagents with unactivated
      secondary alkyl electrophiles: catalytic asymmetric Negishi alpha-alkylations of
      N-Boc-pyrrolidine.
AB  - Although enantioconvergent alkyl-alkyl couplings of racemic electrophiles have
      been developed, there have been no reports of the corresponding reactions of
      racemic nucleophiles. Herein we describe Negishi cross-couplings of racemic alpha
      zincated N-Boc-pyrrolidine with unactivated secondary halides, thus providing a
      one-pot, catalytic asymmetric method for the synthesis of a range of 2
      alkylpyrrolidines (an important family of target molecules) from N-Boc
      pyrrolidine, a commercially available precursor. Preliminary mechanistic studies
      indicated that two of the most straightforward mechanisms for enantioconvergence
      (dynamic kinetic resolution of the organometallic coupling partner and a simple
      beta-hydride elimination/beta-migratory insertion pathway) are unlikely to be
      operative. 

PMID- 23869443
TI  - Trans-vessel gradient of myeloperoxidase in coronary artery disease.
AB  - BACKGROUND: Coronary artery disease (CAD) may reflect generalized inflammation.
      We evaluated leucocyte activation in subjects with and without CAD in different
      vascular compartments. MATERIALS AND METHODS: Patients were divided in two
      groups; subjects without CAD (controls; n = 25) and with stable CAD (n = 52)
      based on coronary angiography. After blood sampling from vessels, cardiovascular
      risk factors and leucocyte activation markers CD11b, CD66b and cytoplasmatic
      myeloperoxidase (MPO) were determined by flow cytometry. RESULTS: Myeloperoxidase
      (MPO) was higher in patients with CAD at all sites compared with controls (188 +/
      7 vs. 210 +/- 12 au for venous (P < 0.05), 178 +/- 7 vs. 212 +/- 12 au for
      femoral artery (P = 0.08), 166 +/- 7 vs. 195 +/- 12 au for abdominal artery (P <
      0.05), 166 +/- 6 vs. 189 +/- 14 au for left coronary (P = 0.08) and 163 +/- 6 vs.
      193 +/- 12 au for the right coronary artery (P < 0.05)). Other markers did not
      differ between the groups. A gradient of inflammation from peripheral vessels to
      the coronaries was found by differences in MPO in both groups; from 210 +/- 12 au
      in the venous compartments towards 189 +/- 14 and 193 +/- 12 au, in the left and
      right coronaries, respectively, for the controls (P = 0.001), and from 188 +/- 7
      au in the venous compartment towards 166 +/- 6 and 163 +/- 6 au in the left and
      right coronaries, respectively, for the patients (P = 0.007). Other leucocyte
      activation markers did not show such a gradient. CONCLUSIONS: There is a
      generalized inflammatory neutrophil gradient for MPO from peripheral vessels
      towards the coronaries in both patients with CAD and controls. However, patients
      with CAD show a higher degree of inflammation, mostly in the coronaries. These
      data strengthen the role of activated neutrophils in CAD.

PMID- 23869444
TI  - Gerontological nurses' perceptions of their rights in Finland.
AB  - BACKGROUND: These are challenging times for gerontological nurses, due to the
      increasing need for older people care services and nursing expertise and to the
      burdensome nature of older people care. These changes also challenge professional
      ethics. Traditionally, literature has focused more on nurses' duties and
      responsibilities, rather than on their rights. AIM: The aim was to explore the
      concept of nurses' rights from the perspective of nurses in gerontological care.
      METHODS: A qualitative study conducted among gerontological nurses (n = 29) in
      the older people care of two publicly provided municipal older people care
      organisations in two mid-range towns in Finland. Participation in the study was
      voluntary, and the participants were recruited in collaboration with a nurse
      executive. The data, collected in 11 interviews (1-4 participants in each) using
      open-ended interview method, were analysed by inductive content analysis.
      FINDINGS: Based on our findings, nurses' rights are an integral part of everyday
      nursing. As professionals, nurses pointed out that their rights are based on
      legislation and ethics, and their rights involve colleagues, managers,
      organisation, and patients and relatives. Their rights were connected to nurses'
      professional expertise and their well-being at work, but at the end, they were a
      factor to improving quality of older people care. This required that nurses'
      rights were taken as visible and elementary part of management. CONCLUSION: On
      the basis of our findings, especially in very demanding areas of nursing, like
      older people care, nurses' rights deserve major visibility and should be taken
      into consideration when planning care.

PMID- 23869445
TI  - The daily intake of Tadalafil 5 mg improves the symptoms of chronic anal fissure.

PMID- 23869448
TI  - The effect of solvatochromism on the interfacial morphology of P3HT-CdS nanowire
      nanohybrids.
AB  - Increasing performance in organic/inorganic bulk heterojunctions hybrid
      photovoltaic systems hinges not only on the structure of the inorganic component
      but also on the morphology of the polymeric component. Changing the morphology of
      the organic component is a facile way of changing the morphology of the interface
      between the inorganic and organic components in the bulk heterojunction system.
      Engineering this interface to more efficiently split photogenerated excitons and
      transport these carriers to electrodes can increase the efficiency of
      photovoltaic devices. In this report, we investigate the effect of solvent
      quality on the morphology of the poly(3-hexylthiophene)-2,5-diyl (P3HT) polymer
      semiconductor interface (solvatochromism). We have found that creating more order
      within the P3HT main chain in solution and prior to deposition has a profound
      effect on the nature of the P3HT-CdS nanowire interface. Solvents with a larger
      difference in solubility parameter, Deltadelta, relative to P3HT, such as
      methanol and isopropanol, create larger rod domains in the P3HT main chain and
      result in larger domains of crystalline P3HT at the interface. Solvents with
      similar solubility parameters as P3HT, such as pyridine and hexanol, create
      relatively shorter rod domains in the main chain and, as a result, nanohybrids
      with reduced crystallinity. The results of this paper further cement the
      importance of manipulating the rod-coil transition in the conducting polymers
      such as P3HT to improve the crystallinity at the polymer-semiconductor interface
      that can easily be scaled up to improve the efficiency of bulk heterojunction
      photovoltatic systems. 

PMID- 23869449
TI  - A new homozygous nonsense mutation in LAMA3A underlying laryngo-onycho-cutaneous
      syndrome.
AB  - Laryngo-onycho-cutaneous (LOC) syndrome is a subtype of autosomal recessive
      junctional epidermolysis bullosa in which there is prominent skin and mucosal
      granulation tissue that can lead to delayed wound healing, laryngeal obstruction
      and blindness. Thus far, all cases are of Punjabi ancestry and have been shown to
      result from a founder mutation in the LAMA3 gene, notably involving a single
      nucleotide insertion mutation in exon 39, which is specific to the LAMA3A
      (designated exon 1 of LAMA3A) and not the LAMA3B1 or LAMA3B2 isoforms. Here, we
      describe a new pedigree with LOC syndrome. Affected individuals (from Iran) have
      the characteristic clinicopathological and molecular features of LOC syndrome:
      prominent granulation tissue (especially affecting the eyes), normal intensity
      laminin-332 immunostaining at the dermal-epidermal junction, and autosomal
      recessive mutations in the LAMA3A-specific exon. The pathogenic mutation is a
      homozygous nonsense mutation, designated p.Gln57X, which just affects the laminin
      alpha3a transcript. These findings therefore expand the molecular basis of LOC
      syndrome. 

PMID- 23869447
TI  - Stem cells and cell therapies in lung biology and diseases: conference report.

PMID- 23869450
TI  - Extent of sample loss on the sampling device and the resulting experimental
      biases when collecting volatile fatty acids (VFAs) in air using sorbent tubes.
AB  - Not all volatile organic compounds (VOCs) are suitable for sampling from air onto
      sorbent tubes (ST) with subsequent analysis by thermal desorption (TD) with gas
      chromatography (GC). Some compounds (such as C2 hydrocarbons) are too volatile
      for quantitative retention by sorbents at ambient temperature, while others are
      too reactive - either for storage stability on the tubes (post-sampling) or for
      thermal desorption/GC analysis. Volatile fatty acids (VFAs) are one of the
      compound groups that present a challenge to sorbent tube sampling. In this study,
      we evaluated sample losses on the inner wall surface of the sorbent tube sampler.
      The sorptive losses of five VFA (acetic, propionic, n-butyric, i-valeric, and n
      valeric acid) were tested using two types of tubes (stainless steel and quartz),
      each packed with three sorbent beds arranged in order of sorbent strength from
      the sampling end of the tube (Tenax TA, Carbopack B, and Carbopack X). It showed
      significantly higher losses of VFAs in both liquid phase and vapor phase when
      using stainless steel tube samplers. These losses were also seen if vapor-phase
      fatty acids were passed through empty stainless steel tubing and increased
      dramatically with increasing molecular weight, e.g., losses of 33.6% (acetic
      acid) to 97.5% (n-valeric acid). Similar losses of VFAs were also observed from
      headspace sampling of cheese products. Considering that stainless steel sampling
      tubes are still used extensively by many researchers, their replacement with
      quartz tubes is recommended to reduce systematic biases in collecting VFA samples
      or in their calibration. 

PMID- 23869451
TI  - Preparation and characterization of nocodazole-loaded solid lipid nanoparticles.
AB  - Nocodazole (NCD) has more carcinogenic effect than similar drugs. Moreover, it
      has low drug release time and high particle size. Solid Lipid Nanoparticles
      (SLNs) have been evaluated for decrease in particle size and therefore increase
      in drug release time, for such drugs. In this study, NCD has been successfully
      incorporated into SLNs systems and remained stable for a period of 90 days. NCD
      structure related to the chemical nature of solid lipid is a key factor to decide
      whether anticarcinogenic agent will be incorporated in the long term and for a
      controlled optimization of active ingredient incorporation and loading, intensive
      characterization of the physical state of the lipid particles were highly
      essential. Thus, NMR, FT-IR, DSC (for thermal behavior) analyses were performed
      and the results did not indicate any problem on stability. Moreover, SLNs were
      decreased size of NCD in addition to increase in time of the drug release. After
      SLN preparation, particle size, polydispersity index, electrical conductivity and
      zeta potential were measured and drug release from NCD-loaded SLNs were
      performed. These values seem to be of the desired range.

PMID- 23869452
TI  - Cushing's syndrome: development of highly potent and selective CYP11B1 inhibitors
      of the (pyridylmethyl)pyridine type.
AB  - Potent and selective CYP11B1 inhibitors could be promising therapeutics for the
      treatment of Cushing's syndrome. Optimization of Ref 1 (5-((1H-imidazol-1
      yl)methyl)-2-phenylpyridine) led to compound 44 (5-((5-methylpyridin-3-yl)methyl)
      2-phenylpyridine) with a 50-fold improved IC50 value of 2 nM toward human CYP11B1
      and an enhanced inhibition of the rat enzyme (IC50 = 2440 nM) compared to Ref 1
      (IC50 > 10000 nM). Furthermore, selectivities over CYP11B2, CYP17, and CYP19 were
      observed, as well as satisfying metabolic stability not only in human and rat
      plasma but also in liver S9 fraction. Investigation of cytotoxicity and
      inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety
      criteria and can be considered for further in vivo evaluation in rats. 

PMID- 23869453
TI  - Introduction to the special issue: drugs, wars, military personnel, and veterans.
AB  - This special issue examines major structural, sociocultural, and behavioral
      issues surrounding substance use and misuse among U.S. military personnel and
      veterans who served in recent military conflicts in Iraq and Afghanistan. This
      introduction provides a brief historical review of the US's experiences of the
      linkages between war and substance use, misuse, and abuse. It then describes how
      the various topics covered in this issue span the military-veteran life course
      and explains the significance of each contribution.

PMID- 23869454
TI  - Trends in binge and heavy drinking, alcohol-related problems, and combat exposure
      in the U.S. military.
AB  - Population-based Department of Defense health behavior surveys were examined for
      binge and heavy drinking among U.S. active duty personnel. From 1998-2008,
      personnel showed significant increases in heavy drinking (15% to 20%) and binge
      drinking (35% to 47%). The rate of alcohol-related serious consequences was 4%
      for nonbinge drinkers, 9% for binge drinkers, and 19% for heavy drinkers.
      Personnel with high combat exposure had significantly higher rates of heavy
      (26.8%) and binge (54.8%) drinking than their counterparts (17% and 45%,
      respectively). Heavy and binge drinking put service members at high risk for
      problems that diminish force readiness and psychological fitness. 

PMID- 23869455
TI  - Prescription opioid initiation, correlates, and consequences among a sample of
      OEF/OIF military personnel.
AB  - Prescription opioid (PO) misuse represents a major health risk for many service
      members and veterans. This paper examines the pathways to misuse among a sample
      of U.S. veterans who recently returned from Iraq and Afghanistan to low-income,
      predominately minority sections of New York City. Recreational PO misuse was not
      common on deployment. Most PO misusers initiated use subsequent to PO use for
      pain management, an iatrogenic pathway. However, most PO users did not misuse
      them. Veterans that misused POs were more likely to have other reintegration
      problems including drug and alcohol use disorders, traumatic brain injury (TBI),
      unemployment, and homelessness.

PMID- 23869446
TI  - Stem cells, cell therapies, and bioengineering in lung biology and diseases.
      Comprehensive review of the recent literature 2010-2012.
AB  - A conference, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases,"
      was held July 25 to 28, 2011 at the University of Vermont to review the current
      understanding of the role of stem and progenitor cells in lung repair after
      injury and to review the current status of cell therapy and ex vivo
      bioengineering approaches for lung diseases. These are rapidly expanding areas of
      study that provide further insight into and challenge traditional views of
      mechanisms of lung repair after injury and pathogenesis of several lung diseases.
      The goals of the conference were to summarize the current state of the field, to
      discuss and debate current controversies, and to identify future research
      directions and opportunities for basic and translational research in cell-based
      therapies for lung diseases. The goal of this article, which accompanies the
      formal conference report, is to provide a comprehensive review of the published
      literature in lung regenerative medicine from the last conference report through
      December 2012. 

PMID- 23869457
TI  - The effects of the military's antidrug policies over the life course: the case of
      past-year hallucinogen use.
AB  - We analyze long-term trends in past-year hallucinogen use among veterans as
      compared to nonveterans. This topic is theoretically strategic because the
      military adopted stringent and successful antidrug policies in the mid-1980s,
      which serves as a natural experiment to examine the potential long-term impact of
      comprehensive drug policies on illegal drug use. Drawing on self-reported data
      from the National Survey of Drug Use and Health in years 1985, 1988, and 1990
      2010, the analysis uses age-period-cohort analysis to update trends in past-year
      hallucinogen use and to examine the impact of veteran status. Results are
      consistent with the hypothesis that a stringent antidrug policy can lead to a
      life-long reduction in hallucinogen use. Among birth cohorts who were young
      adults immediately before the implementation of the antidrug policies (those in
      the 1960-1964 birth cohort) odds of past-year hallucinogen use were twice as high
      for veterans as compared to nonveterans over the life course. This difference
      disappeared among birth cohorts that were young adults after the antidrug
      policies were implemented, when the prevalence of past-year hallucinogen use
      would be expected to be higher for veterans because of their significantly higher
      rates of illegal drug use in adolescence. After the drug-testing policies were
      implemented veterans actually had significantly lower prevalence of past-year
      hallucinogen use in comparison to nonveterans among the subgroup of respondents
      who reported a history of illegal drug use before age 18 (OR = .77, p < .01).
      These trends across veterans and nonveterans were not explained by trends in
      recruits' tendencies for illegal drug use. These findings point to service in
      today's armed forces as a turning point that, overall, leads to a lasting,
      lifelong reduction in substance use. 

PMID- 23869456
TI  - Traumatic brain injury among U.S. active duty military personnel and negative
      drinking-related consequences.
AB  - This study used the 2008 Department of Defense Survey of Health Related Behaviors
      among Active Duty Military Personnel to determine whether traumatic brain injury
      (TBI) is associated with past year drinking-related consequences. The study
      sample included currently drinking personnel who had a combat deployment in the
      past year and were home for >=6 months (N = 3,350). Negative binomial regression
      models were used to assess the incidence rate ratios of consequences, by TBI
      level. Experiencing a TBI with a loss of consciousness for more than 20 minutes
      was significantly associated with consequences independent of demographics,
      combat exposure, posttraumatic stress disorder, and binge drinking. The study's
      limitations are noted. 

PMID- 23869458
TI  - Explaining differences in hepatitis C between U.S. veterans and nonveterans in
      treatment for substance abuse: results from a regression decomposition.
AB  - Hepatitis C virus (HCV) infection is common among people with substance abuse
      histories and a burden for U.S. veterans in particular. This study compares self
      reported HCV between 1,652 veterans and 48,013 nonveterans who received public
      sector substance abuse treatment in Los Angeles between 2006 and 2010. A higher
      percentage of veterans than nonveterans reported HCV (6.5% vs. 3.8%, p < .0001).
      Homelessness and mental illness explained, respectively, 8.6% and 7.1% of the
      difference in HCV between the two groups, adjusting for other variables. Reducing
      homelessness and mental illness among veterans may also help reduce the excess
      burden of HCV in this population. 

PMID- 23869459
TI  - Rationale and methods of the Substance Use and Psychological Injury Combat Study
      (SUPIC): a longitudinal study of Army service members returning from deployment
      in FY2008-2011.
AB  - The Substance Use and Psychological Injury Combat Study (SUPIC) will examine
      whether early detection and intervention for post-deployment problems among Army
      Active Duty and National Guard/Reservists returning from Iraq or Afghanistan are
      associated with improved long-term substance use and psychological outcomes. This
      paper describes the rationale and significance of SUPIC, and presents demographic
      and deployment characteristics of the study sample (N = 643,205), and self
      reported alcohol use and health problems from the subsample with matched post
      deployment health assessments (N = 487,600). This longitudinal study aims to
      provide new insight into the long-term post-deployment outcomes of Army members
      by combining service member data from the Military Health System and Veterans
      Health Administration. 

PMID- 23869460
TI  - Substance use and other mental health disorders among veterans returning to the
      inner city: prevalence, correlates, and rates of unmet treatment need.
AB  - Estimates of substance use and other mental health disorders of veterans (N =
      269) who returned to predominantly low-income minority New York City
      neighborhoods between 2009 and 2012 are presented. Although prevalences of
      posttraumatic stress disorder, traumatic brain injury, and depression clustered
      around 20%, the estimated prevalence rates of alcohol use disorder, drug use
      disorder, and substance use disorder were 28%, 18%, and 32%, respectively. Only
      about 40% of veterans with any diagnosed disorder received some form of
      treatment. For alcohol use disorder, the estimate of unmet treatment need was
      84%, which is particularly worrisome given that excessive alcohol use was the
      greatest substance use problem. 

PMID- 23869461
TI  - Opioid and other substance misuse, overdose risk, and the potential for
      prevention among a sample of OEF/OIF veterans in New York City.
AB  - This paper describes veterans' overdose risks and specific vulnerabilities
      through an analysis of qualitative data collected from a sample of recently
      separated, formerly enlisted OEF/OIF veterans in the New York City area. We
      illustrate how challenges to the civilian readjustment process such as
      homelessness, unemployment, and posttraumatic stress disorder can render veterans
      at increased risk for negative health consequences and then present veterans'
      perspectives as they outline several innovative solutions to these obstacles. We
      conclude by discussing several overdose prevention efforts currently underway and
      how they might be adapted to meet the opioid and substance misuse challenges
      veterans face. 

PMID- 23869462
TI  - Reaching soldiers with untreated substance use disorder: lessons learned in the
      development of a marketing campaign for the Warrior Check-Up study.
AB  - The Warrior Check-Up, a confidential telephone-delivered intervention, is
      designed to reach active-duty soldiers with untreated substance-use disorder at a
      large U.S. military base. This paper describes the development and successful
      implementation of the study's marketing strategies at the recruitment period's
      midpoint (2010-2012). Qualitative analyses of focus groups (n = 26) and survey
      responses (n = 278) describe the process of campaign design. Measures of
      demographics, media exposure, post-traumatic stress, anxiety and depression
      gathered from callers (n = 172) are used in quantitative analysis assessing the
      campaign's success in reaching this population. Implications, limitations, and
      suggestions for future research are discussed. Department of Defense provided
      study funding.

PMID- 23869463
TI  - Catch, treat, and release: Veteran Treatment Courts address the challenges of
      returning home.
AB  - After a decade of war, there is a great need for treatment and alternatives to
      incarceration for justice-involved veterans. U.S. military service members are
      returning from combat with substantial mental health challenges, which increase
      the potential for justice involvement. Veteran Treatment Courts are starting
      across the nation to meet this need for therapeutic justice. These problem
      solving courts provide access to treatment and motivation for engagement.
      Preliminary evidence from a Substance Abuse and Mental Health Services
      Administration-funded evaluation suggests that significant improvements in
      posttraumatic stress disorder and substance use are just a few of the positive
      outcomes that these courts may help veterans achieve. 

PMID- 23869464
TI  - Electron-attachment-induced DNA damage: instantaneous strand breaks.
AB  - Low energy electron-attachment-induced damage in DNA, where dissociation channels
      may involve multiple bonds including complex bond rearrangements and significant
      nuclear motions, is analyzed here. Quantum mechanics/molecular mechanics (QM/MM)
      calculations reveal how rearrangements of electron density after vertical
      electron attachment modulate the position and dynamics of the atomic nuclei in
      DNA. The nuclear motions involve the elongation of the P-O (P-O(3') and P-O(5'))
      and C-C (C(3')-C(4') and C(4')-C(5')) bonds for which the acquired kinetic energy
      becomes high enough so that the neighboring C(3')-O(3') or C(5')-O(5')
      phosphodiester bond may break almost immediately. Such dynamic behavior should
      happen on a very short time scale, within 15-30 fs, which is of the same order of
      magnitude as the time scale predicted for the excess electron to localize around
      the nucleobases. This result indicates that the C-O phosphodiester bonds can
      break before electron transfer from the backbone to the base.

PMID- 23869465
TI  - Enhanced induction of cell cycle arrest and apoptosis via the mitochondrial
      membrane potential disruption in human U87 malignant glioma cells by aloe emodin.
AB  - Aloe emodin, one of the active compounds found in Aloe vera leaves, plays an
      important role in the regulation of cell growth and death. It has been reported
      to promote the anti-cancer effects in various cancer cells by inducing apoptosis.
      However, the mechanism of inducing apoptosis by this agent is poorly understood
      in glioma cells. This research is to investigate the apoptosis and cell cycle
      arrest inducing by aloe emodin on U87 human malignant glioma cells. Aloe emodin
      showed a time- and dose-dependent inhibition of U87 cells proliferation and
      decreased the percentage of viable U87 cells via the induction of apoptosis.
      Characteristic morphological changes, such as the formation of apoptotic bodies,
      were observed with confocal microscope by Annexin V-FITC/PI staining, supporting
      our viability study and flow cytometry analysis results. Our data also
      demonstrated that aloe emodin arrested the cell cycle in the S phase and promoted
      the loss of mitochondrial membrane potential in U87 cells that indicated the
      early event of the mitochondria-induced apoptotic pathway. 

PMID- 23869467
TI  - Giant thermovoltage in single InAs nanowire field-effect transistors.
AB  - Millivolt range thermovoltage is demonstrated in single InAs nanowire based field
      effect transistors. Thanks to a buried heating scheme, we drive both a large
      thermal bias DeltaT > 10 K and a strong field-effect modulation of electric
      conductance on the nanostructures. This allows the precise mapping of the
      evolution of the Seebeck coefficient S as a function of the gate-controlled
      conductivity sigma between room temperature and 100 K. Based on these
      experimental data a novel estimate of the electron mobility is given. This value
      is compared with the result of standard field-effect based mobility estimates and
      discussed in relation to the effect of charge traps in the devices. 

PMID- 23869466
TI  - Missed office visits and risk of mortality among HIV-infected subjects in a large
      healthcare system in the United States.
AB  - Linkage and retention in care soon after HIV diagnosis improves clinical
      outcomes. Conversely, missed visits after diagnosis are associated with increased
      mortality in the public care setting. We analyzed mortality among newly diagnosed
      HIV patients >=18 years old in a large private care setting between 01/01/1997
      and 12/31/2009, comparing patients who missed visits in their first year
      following diagnosis (index period) with those who did not. Patients who died
      during the index period were excluded. Hazard ratios (HR) for association of
      missed visits and mortality were obtained by Cox proportional hazards regression,
      adjusting for patient demographics, CD4+ counts, and AIDS-defining conditions
      (CDC, 1993) at diagnosis. We also evaluated risk factors of missed visits by
      multivariable logistic regression. 2811 patients were included, of whom 65% had
      >=1 missed visit, and 226 patients died during follow-up. Patients with >=1
      missed visit had a 71% increased mortality risk (HR=1.71, p=0.001) with 12%
      increased rate per missed visit (HR=1.12, p<0.001). Factors associated with
      missed visits were younger age (OR=1.69 compared to 60+ years), Black and Latino
      race/ethnicity (OR=1.54, 1.48 respectively, compared to Caucasians), injection
      drug use (OR=2.50 compared to men who have sex with men), and lower CD4+ (OR=1.43
      for CD4+ 100-199 cells/MUL, OR=1.39 for 50-99 cells/MUL, and OR=1.63 for CD4+ <50
      cells/MUL, compared with CD4+ >500 cells/MUL). In an insured patient population,
      missed visits in the first year of HIV care are common and associated with
      increased mortality. Early retention in HIV care is critical to improving
      outcomes.

PMID- 23869468
TI  - A hyperactive postprandial response in the neorectum--the clue to low anterior
      resection syndrome after total mesorectal excision surgery?
AB  - AIM: To investigate neorectal properties regarding biomechanical, sensory and
      postprandial response in patients after total mesorectal excision without
      neoadjuvant radiotherapy in groups of no low anterior resection syndrome (LARS)
      patients and major LARS patients. METHOD: Patients without LARS (n = 9) and
      patients with major LARS (n = 23) were investigated by multimodal rectal
      stimulation and standard anorectal physiological tests, and results were
      compared. RESULTS: Patients with major LARS had an increased postprandial
      response with a significant increase in pressure in the neorectum after a meal
      compared with patients without LARS (P = 0.017). No biomechanical differences
      could be detected. CONCLUSION: Low anterior resection syndrome seems to be caused
      by physiological changes due to neural damage more than structural changes in the
      ano-neorectum.

PMID- 23869469
TI  - Transapical implantation of the SAPIEN 3 valve.
AB  - We report two cases of high-risk aortic stenosis treated with the SAPIEN 3 valve.
      This is the first procedure performed with this type of valve through the
      transapical approach. This new balloon-expandable valve incorporates a lower
      profile cobalt-chromium stent and an additional outer skirt to enhance
      paravalvular sealing. The procedure was performed without complications and no
      paravalvular leak was detected in control echocardiogram at follow-up.

PMID- 23869470
TI  - Sudden unexpected death during pediatric anesthesia: from status thymico
      lymphaticus to silent cardiomyopathy.

PMID- 23869471
TI  - Cutaneous lesions associated with dual infection caused by canine distemper virus
      and orthopoxvirus in a domestic cat.
AB  - BACKGROUND: Within the context of an increased epidemiological pressure caused by
      canine distemper virus (CDV) in Switzerland together with a potential re
      emergence of endemic pathogens such as orthopoxviruses (OPXV), dual infections
      are possible among susceptible species. OBJECTIVE: To describe a case of
      concurrent CDV and OPXV infection in a cat. ANIMAL: A 5-year-old, neutered male
      cat was presented with erythema, crusts and ulcerations around the left eye. High
      grade pruritus and a severe conjunctivitis were also present. METHODS: Formalin
      fixed skin biopsy samples were obtained from lesional skin. Histopathology, CDV
      immunohistochemistry and CDV and OPXV RT-PCR were performed. RESULTS:
      Histopathological examination showed severe epidermal necrosis extending to the
      follicular walls and a dermal infiltration, predominantly eosinophilic.
      Intranuclear and intracytoplasmic eosinophilic inclusion bodies were visible in
      the wall of affected hair follicles, with occasional formation of syncytia. The
      RT-PCR revealed the contextual presence of both CDV and OPXV. Scattered cells
      stained positive for CDV by immunohistochemistry. CONCLUSION AND DISCUSSION: Dual
      infections with CDV and OPXV, although rare, may occur and represent additional
      differential diagnoses for ulcerative skin lesions in cats.

PMID- 23869472
TI  - Robust nonfitting way to determine mass diffusivity and initial concentration for
      VOCs in building materials with accuracy estimation.
AB  - This paper presents a novel procedure for estimating mass diffusivity and initial
      concentration for VOCs in building materials. In contrast to methods that fit
      data to an organic emission model, this new method determines these two
      parameters by two observations from a chamber test in a nonfitting and sequential
      way, which defines a well-posed problem and requires no iterative procedure as
      well as is robust to initial guess and random uncertainties. The most outstanding
      feature of this method is that multiple estimates of the parameters can be
      obtained when more than two experimental data are available; thus, these
      estimates constitute a sample of population of parameter estimates involving
      experimental errors. The averages of the sample can be regarded the best
      estimates of the parameters, and, more importantly, variances (standard
      deviations) and confidence intervals can be readily and naturally estimated
      making no assumption about the distribution of experimental errors. Two easy and
      direct ways are suggested for determining confidence limits: one is percentile
      method, and the other is the normal approximation. This feature highlights the
      major difference between the new method and common curve-fitting procedures that
      generally assume random errors being Gaussian distribution. 

PMID- 23869473
TI  - Sequence-independent processing site of the C-terminal domain (CTD) influences
      maturation of the RgpB protease from Porphyromonas gingivalis.
AB  - The Gram-negative periodontal pathogen Porphyromonas gingivalis produces a family
      of outer membrane-anchored proteases, the gingipains, shown to play an essential
      role in virulence of the organism. The C-terminal domain (CTD) of gingipains and
      other secreted proteins is known to be the targeting signal for maturation and
      translocation of the protein through the outer membrane. The CTD is subsequently
      cleaved during the secretion process. Multiple alignment of various CTDs failed
      to define a consensus sequence at the putative CTD processing site. Using
      mutagenesis, we were able to show that cleavage at the site is not dependent on a
      specific residue and that recognition of the site is independent of local
      sequence. Interestingly, length of the junction between the CTD and adjacent Ig
      like subdomain has a critical influence on post-translational glycan modification
      of the protein, whereby insertion of additional residues immediately N-terminal
      to the cleavage site results in failure of glycan modification and release of
      soluble protease into the culture medium. Various hypotheses are presented to
      explain these phenomena. Knowledge of the role CTDs play in maturation of
      gingipains has broader application for understanding maturation of CTD homologues
      expressed by bacteria of the Bacteriodetes phylum. 

PMID- 23869474
TI  - Combined charge carrier transport and photoelectrochemical characterization of
      BiVO4 single crystals: intrinsic behavior of a complex metal oxide.
AB  - Bismuth vanadate (BiVO4) is a promising photoelectrode material for the oxidation
      of water, but fundamental studies of this material are lacking. To address this,
      we report electrical and photoelectrochemical (PEC) properties of BiVO4 single
      crystals (undoped, 0.6% Mo, and 0.3% W:BiVO4) grown using the floating zone
      technique. We demonstrate that a small polaron hopping conduction mechanism
      dominates from 250 to 400 K, undergoing a transition to a variable-range hopping
      mechanism at lower temperatures. An anisotropy ratio of ~3 was observed along the
      c axis, attributed to the layered structure of BiVO4. Measurements of the ac
      field Hall effect yielded an electron mobility of ~0.2 cm(2) V(-1) s(-1) for Mo
      and W:BiVO4 at 300 K. By application of the Gartner model, a hole diffusion
      length of ~100 nm was estimated. As a result of low carrier mobility, attempts to
      measure the dc Hall effect were unsuccessful. Analyses of the Raman spectra
      showed that Mo and W substituted for V and acted as donor impurities. Mott
      Schottky analysis of electrodes with the (001) face exposed yielded a flat band
      potential of 0.03-0.08 V versus the reversible H2 electrode, while incident
      photon conversion efficiency tests showed that the dark coloration of the doped
      single crystals did not result in additional photocurrent. Comparison of these
      intrinsic properties to those of other metal oxides for PEC applications gives
      valuable insight into this material as a photoanode.

PMID- 23869475
TI  - Adding silver to the rainbow: the development of the nurses' health education
      about LGBT elders (HEALE) cultural competency curriculum.
AB  - AIM: In 2009, the Howard Brown Health Center received funding from the US
      Department of Health and Human Services, and Health Resources and Services
      Administration to develop and disseminate a peer-reviewed, six-module curriculum
      entitled, Health Education about LGBT (lesbian, gay, bisexual and transgender)
      Elders (HEALE). BACKGROUND: The HEALE curriculum targets nurses and health-care
      staff and is focused on the treatment of LGBT elders, a population that is
      largely misunderstood and discriminated against in health-care settings. The
      HEALE curriculum was presented in hospital academic centres, community-based
      clinics and nursing homes over a three-year period, and training staff provided
      education to over 500 nurses and health-care providers. METHOD: A pre-test and
      post-test was administered to participants, and all data were collected and
      archived to measure knowledge gained. Participants also completed an evaluation
      at the conclusion of the training to report change in personal attitude and
      individual response to the curriculum. RESULTS AND CONCLUSIONS: From March 2011
      to June 2012, 848 individuals attended HEALE curriculum sessions at 23 locations
      in Chicago and surrounding areas. Participants were 40% white, 25% black, 9%
      Hispanic/Latino and 25% Asian race/ethnicity. The majority of participants were
      female and approximately 25% were under the age of 30 years. There were
      statistically significant gains in knowledge in each of the six modules both in
      nursing home/home health-care settings and in hospital/educational settings,
      although participants in nursing home/home health care settings had lower pre
      test scores and smaller knowledge gains in each of the six modules than those in
      hospital/educational settings. Mean increases ranged from 6.4 points (an 8.7%
      increase) in module 1-14.6 points (a 26.2% increase) in Module 6 (P < 0.01).
      IMPLICATIONS FOR NURSING MANAGEMENT: The HEALE curriculum sets a standard for
      best practices in nursing management and for LGBT cultural competency in
      geriatric education. As such, implementation of this cultural competency training
      will go a long way to establish fundamental concepts regarding LGBT elder care
      and provide long-term strategies for providing culturally sensitive patient care.

PMID- 23869476
TI  - Incidence and prognosis of dysnatraemia in critically ill patients: analysis of a
      large prevalence study.
AB  - BACKGROUND: The objective of this study is to assess the impact of dysnatraemia
      on mortality among intensive care unit (ICU) patients in a large, international
      cohort. MATERIAL AND METHODS: Analysis of the Extended Prevalence of Infection in
      Intensive Care (EPIC II) study, a 1-day (8 May 2007) worldwide multicenter,
      prospective point prevalence study. Hyponatraemia was categorized as mild (130
      134 mM/L), moderate (125-129 mM/L) or severe (< 125 mM/L). Hypernatraemia was
      also categorized as mild (146-150 mM/L), moderate (151-155 mM/L) or severe (> 155
      mM/L). Patients with normal serum sodium (135-145 mM/L) constituted the reference
      group. The main outcome was hospital mortality. Analysis was conducted separately
      for patients admitted on the study day (25.8%) and those already present on the
      ICU (74.2%). RESULTS: Serum sodium was measured in 13 276 of the 13 796 patients
      (96.2%). A total of 3815 patients (28.7%) had dysnatraemia: 12.9% with
      hyponatraemia and 15.8% with hypernatraemia. The prevalence of dysnatraemia was
      significantly greater in patients already present on the ICU prior to the study
      day than for those just admitted (13.1% vs. 12.3% for hyponatraemia and 17.1% vs.
      12.1% for hypernatraemia, both P < 0.001). Hospital mortality rates were higher
      in patients with dysnatraemia than in those with normal sodium levels and were
      directly related to the severity of hypo- and hypernatraemia. This association
      between dysnatraemia and mortality was similar in infected and noninfected
      patients (P = 0.061). CONCLUSIONS: Dysnatraemia is more frequent during the ICU
      stay than on the day of admission. Dysnatraemia in the ICU - even mild - is an
      independent predictor of increased hospital mortality.

PMID- 23869477
TI  - Stomach gas analyses in canine acute gastric dilatation with volvulus.
AB  - BACKGROUND: The origin of the gas in the stomachs of dogs with acute gastric
      dilatation or gastric dilatation with volvulus (GDV) often is disputed.
      HYPOTHESIS: We tested the hypothesis that gaseous distention resulted from
      aerophagia. ANIMALS: Ten cases of GDV that were submitted to an emergency clinic
      were sampled intraoperatively. METHODS: With the abdomen open, the needle of a
      vacutainer blood collection set was inserted into the distended stomach, and gas
      was collected into 10 mL glass vacutainer vials with rubber stoppers. These were
      stored at room temperature for 1-7 days and then analyzed by gas chromatography
      and mass spectroscopy. RESULTS: CO2 composition ranged from 13 to 20%. One dog
      had an H2 concentration of 29%. CONCLUSIONS: Because the CO2 content of
      atmospheric air is less than 1%, these findings suggest that the gaseous gastric
      distention in GDV is not the result of aerophagia.

PMID- 23869478
TI  - Role of routine 16b1 lymph node biopsy in the management of gallbladder cancer:
      an analysis.
AB  - BACKGROUND: Involvement of the 16b1 (interaortocaval) lymph node (LN) in
      gallbladder cancer (GBC) is considered to represent metastatic disease. Although
      this is universally accepted, the role of routine frozen-section
      histopathological examination (HPE) of the 16b1 LN in the management of GBC has
      not been previously reported. METHODS: A prospective study (August 2009-November
      2011) using routine biopsy of 16b1 LNs and frozen-section HPE prior to radical
      resection in patients deemed operable on preoperative evaluation and staging
      laparoscopy was carried out. RESULTS: Of the 451 GBC patients assessed, 251
      (55.7%) were deemed operable on preoperative imaging. Of these, 68 (27.1%) were
      found to have disseminated disease on staging laparoscopy/laparotomy. Of the 183
      patients in whom 16b1 LN biopsy was performed, 34 (18.6%) had evidence of
      metastases on frozen-section HPE and the planned surgical resection was abandoned
      (Group A). Of the remaining 149 patients (Group B), 142 (95.3%) underwent
      curative resection and seven (4.7%) were found to be unresectable as a result of
      locoregionally advanced disease. A comparison of findings in Group A with those
      in Group B showed no significant difference in the clinical stage of the tumour.
      The proportions of patients with jaundice, elevated carcinoembryonic antigen
      (CEA) and carbohydrate antigen (CA) 19-9 levels were significantly higher in
      Group A than in Group B (P = 0.008, P = 0.012 and P = 0.023, respectively).
      CONCLUSIONS: Routine 16b1 LN biopsy prevented non-therapeutic radical resection
      and its associated morbidity in 18.6% of patients deemed resectable on
      preoperative imaging and staging laparoscopy. The yield was higher in patients
      with jaundice and elevated preoperative tumour marker levels.

PMID- 23869479
TI  - Comorbid psychopathology rates in children diagnosed with autism spectrum
      disorders according to the DSM-IV-TR and the proposed DSM-5.
AB  - OBJECTIVE: To investigate differences in comorbid psychopathology rates between
      individuals who meet criteria of Autism Spectrum Disorders (ASDs) according to
      DSM-5 or the DSM-IV-TR. METHODS: Comorbid psychopathology was measured using the
      Autism Spectrum Disorders- Comorbid for Children. 424 individuals between the
      ages of 2 and 18 years of age; including children who met criteria for an ASD
      according to the DSM-5, the DSM-IV-TR only, and a control group that did not meet
      either set of criteria. RESULTS: Of the ASD participants, 36% would no longer
      meet criteria according to proposed DSM-5. Comorbidity rates for the ASD groups
      were significantly different from the control group; however, ASD groups were not
      significantly different in terms of total comorbid psychopathology. CONCLUSION:
      The results elucidate the need for further research regarding services and
      treatments for those individuals that will no longer meet criteria for an ASD but
      still have significant rates of comorbid psychopathology.

PMID- 23869480
TI  - Underlying heart disease and microbiological spectrum of adult infective
      endocarditis in one Chinese university hospital: a 10-year retrospective study.
AB  - BACKGROUND AND AIM: To identify the underlying heart disease and microbiological
      pathogen associated with infective endocarditis (IE) in Chinese patients in one
      university hospital over a 10-year period. METHODS: We recruited 115 adult
      patients admitted to Peking University First Hospital from 2002 to 2011 who were
      diagnosed with definite IE. Statistical analysis was performed to analyse data on
      demographics, clinical and laboratory findings, as well as microbiological
      pathogens. RESULTS: The most common underlying heart diseases for IE were
      congenital heart disease (24.3%) followed by degenerative valvular disease
      (17.4%). Aortic (44.3%) and mitral (43.5%) valves were most frequently affected.
      The right-sided IE cases were all found in patients with congenital heart
      disease. The age of patients was younger in right-sided cases than that in left
      sided ones (P = 0.001). There was no difference in the mortality among groups
      with different underlying heart disease (P = 0.841). Forty-four (38.3%) patients
      were infected with viridans group streptococci. The isolation rate of
      staphylococci in right-sided IE was higher than that in the left-sided IE group
      (P = 0.021). More than 85% of streptococci were susceptible to beta-lactams.
      CONCLUSIONS: Congenital heart disease and degenerative valvular disease have
      overtaken rheumatic heart disease as the major underlying heart diseases
      associated with IE. Viridans group streptococci are the most common microbial
      cause of IE.

PMID- 23869481
TI  - Photodecomposition of ferrocenedicarboxylic acid in methanol to form an
      electroactive infinite coordination polymer and its application in
      bioelectrochemistry.
AB  - Accurately characterizing the product of photodecomposition of ferrocene
      derivatives remains a longstanding challenge due to its structural complexity and
      strong dependence on the solvent and the substituent. Herein, photodecomposition
      of ferrocenedicarboxylic acid (FcDC) in methanol is found for the first time to
      form an electroactive infinite coordinate polymer (ICP) with uniform size, good
      water stability and photostability, and excellent electrochemical activity. The
      possible mechanism for the ICP formation is proposed based on the fission of the
      Fe-ring bond and deprotonation of FcDC under light irradiation. The dissociated
      Fe(2+) is first oxidized to Fe(3+) that consequently coordinates with the
      deprotonated ferrocene dicarboxylate to produce ICP nanoparticles. This work not
      only provides a new insight into the product formation of the photodecomposition
      of ferrocene derivatives but also offers a mild and simple route to the synthesis
      of electroactive ICPs. 

PMID- 23869482
TI  - Phaeolschidins A-E, five hispidin derivatives with antioxidant activity from the
      fruiting body of Phaeolus schweinitzii collected in the Tibetan Plateau.
AB  - Five new hispidin derivatives, phaeolschidins A-E (1-5), as well as two known
      natural products, pinillidine (6) and hispidin (7), were isolated from the
      fruiting bodies of Phaeolus schweinitzii collected in the Tibetan Plateau. The
      structures of the new compounds were elucidated by spectroscopic methods.
      Phaeolschidins A-D (1-4) are new bishispidins. Phaeolschidin E (5) is a new class
      of hispidin derivative in which one pyrrolidin-2-one moiety was linked to C-3 of
      hispidin. The antioxidant activity of 1-7 was evaluated using three methods: the
      DPPH scavenging assay, the total antioxidant capacity assay, and the lipid
      peroxidation assay. Hispidin showed the strongest antioxidant activity of all
      tested compounds. This is the first report of secondary metabolites from the
      fungus P. schweinitzii. 

PMID- 23869483
TI  - Quantification-based mass spectrometry imaging of proteins by parafilm assisted
      microdissection.
AB  - MALDI mass spectrometry imaging (MALDI-MSI) was presented as a good strategy to
      highlight regions presenting specific phenotypes based on molecular content. The
      proteins present in the different areas can be identified by MALDI MSI; however,
      the number of protein identifications remains low in comparison with classical MS
      based proteomics approaches. To overcome this, a new strategy, involving the
      microdissection of tissue sections mounted on parafilm M-covered glass slides, is
      presented. Extraction and fractionation of proteins from a specific region of
      interest were investigated, leading to the identification of more than 1000
      proteins from each microdissected piece. The strength of this cheap technique
      lies in the facile excision of millimeter-sized portions from the tissue allowing
      for the identification of proteins from cells of a specific phenotype obtained
      from the MALDI MS imaging-based molecular classification using hierarchical
      clustering. This approach can be extended to whole tissue sections in order to
      generate images of the section based on label-free quantification obtained from
      identification data. As a proof of concept, we have studied a tissue mounted on a
      parafilm M-covered glass slide, cut it into regular pieces, and submitted each
      piece to identification and quantification according to the developed parafilm
      assisted microdissection (PAM) method. Images were then reconstructed by relative
      quantification of identified proteins based on spectral counting of the peptides
      analyzed by nanoLC-MS and MS/MS. This strategy of quantification-based MSI offers
      new possibilities for mapping a large number of high and low abundance proteins. 

PMID- 23869484
TI  - A novel high-pressure precipitation tandem homogenization technology for drug
      nanocrystals production - a case study with ursodeoxycholic acid.
AB  - To overcome the limitations of the conventional particle size reduction
      technologies, a novel combinative particle size reduction method for the
      effective production of homogeneous nanosuspensions was investigated.
      Ursodeoxycholic acid, a poorly soluble drug representative, was tried to prepare
      nanosuspension by homogenization technology and high-pressure precipitation
      tandem homogenization technology. It was shown that the combinative approach
      could significantly improve the particle size reduction effectiveness over
      conventional homogenization approach. The Box-Behnken design analysis for process
      optimization revealed that the acceptable UDCA-NS was obtained wherein the
      optimal values of A, B, C and D were 10%, 500 bar, 0.125 and 600 bar,
      respectively. SEM results demonstrated that no significant aggregation or
      crystals growth could be observed in the freeze-dried UDCA nanocrystals. The DSC
      and XRD results showed that UDCA remained in a crystalline state. Dissolution
      velocities of the freeze-dried UDCA-NS powder were distinctly superior compared
      to those of the crude powder and physical mixture. The high-pressure
      precipitation tandem homogenization technology can be a good choice for
      nanosuspension preparation of poorly soluble UDCA, due to high efficiency of
      particle size reduction.

PMID- 23869485
TI  - Structural insight into a novel human CCR5-V130I variant associated with
      resistance to HIV-1 infection.
AB  - We report the identification of a novel CC chemokine receptor 5 (CCR5) variant
      that seems associated with resistance to HIV-1 infection. The V130I mutation of
      the CCR5 receptor is located in the intracellular loop ICL2 known as DRY box and
      described in the literature as a nonsynonymous mutation present in nonhuman
      primates group. Extensive molecular modeling and dynamics simulations were
      performed to elucidate the mechanism by which the V130I mutation may induce
      conformational change of the CCR5 folding protein and prevent the interaction
      with the beta-arrestin protein. Our study provides new mechanistic insight into
      how a specific mutation in the regulatory domain of CCR5 might alter the
      structural folding of the DRY box and the possible ICL2 loop binding with the
      beta-arrestin protein, as described in our previous computational study. The
      results from our large-scale simulations complement recent experimental results
      and clinical features and offer useful insights into the mechanism behind CCR5
      protein folding and signal transduction. In order for HIV, the entry of the virus
      to the cells must fuse with the CCR5 receptor that sits on the surface of T
      helper immune cells. The described V130I mutation in the gene encoding the CCR5
      protein may results in a defective CCR5-Arrestin binding complex that blocks
      entry of the virus. 

PMID- 23869487
TI  - Ultrathin W18O49 nanowire assemblies for electrochromic devices.
AB  - Ordered W18O49 nanowire thin films were fabricated by Langmuir-Blodgett (LB)
      technique in the presence of poly(vinyl pyrrolidone) coating. The well-organized
      monolayer of W18O49 nanowires with periodic structures can be readily used as
      electrochromic sensors, showing reversibly switched electrochromic properties
      between the negative and positive voltage. Moreover, the electrochromism
      properties of the W18O49 nanowire films exhibit significant relationship with
      their thickness. The coloration/bleaching time was around 2 s for the W18O49
      nanowire monolayer, which is much faster than the traditional tungsten oxide
      nanostructures. Moreover, the nanowire devices display excellent stability when
      color switching continues, which may provide a versatile and promising platform
      for electrochromism device, smart windows, and other applications. 

PMID- 23869486
TI  - Magnetic resonance enterography in Crohn's disease: a comparison with the
      findings at surgery.
AB  - AIM: Magnetic resonance (MR) enterography is a radiation-free small bowel
      investigation which identifies luminal and extra-luminal pathology in patients
      with Crohn's disease. Most studies have validated MR against conventional
      radiology. We evaluated the results of MR enterography by comparison with
      findings at elective surgery for patients with Crohn's disease, including complex
      pathology. METHOD: Between January 2007 and March 2012 the results of
      preoperative MR enterography for Crohn's disease in consecutive patients in one
      unit were compared with the detailed findings at surgery. RESULTS: Fifty-one
      patients underwent 55 laparotomies during the study period. MR enterography
      identified the presence of Crohn's disease in the distal ileum in 33/34 patients,
      in the proximal ileum in 7/12 patients, in the jejunum in 7/8 patients, in the
      large bowel in 10/11 patients and in the duodenum in one of two patients. MR
      enterography identified ileo-enteric fistula in 10/12 patients, ileosigmoid
      fistula in all of seven patients and other fistulae in 10/11 patients. An abscess
      was identified on MR enterography in eight of nine patients. Within abnormal
      distal ileal segments, the mean contrast enhancement ratio of acute inflammation
      was 2.39 +/- 0.59 compared with 1.82 +/- 0.63 (P < 0.05) in segments with
      fibrosis only. CONCLUSION: Magnetic resonance enterography identifies small bowel
      Crohn's disease with an accuracy similar to or better than those of previously
      published series. Fistulation, abscess formation and large bowel disease can be
      reliably identified and disease activity assessed. Normal, uninvolved small bowel
      length can also be measured. Discrete proximal small bowel lesions may not always
      be detected. In our practice, MR enterography has replaced conventional radiology
      in the assessment of symptomatic patients with Crohn's disease.

PMID- 23869488
TI  - Evo-Devo-Neuro approach to behavior.

PMID- 23869489
TI  - Boiling temperature as a scaling parameter for the microscopic relaxation
      dynamics in molecular liquids.
AB  - At sufficiently high temperatures, the center-of-mass microscopic diffusion
      dynamics of liquids is characterized by a single component, often with weak
      temperature dependence. In this regime, the effective cage made by the neighbor
      particles cannot be sustained and readily breaks down, enabling long-range
      diffusion. As the temperature is decreased, the cage relaxation becomes impeded,
      leading to a higher viscosity with more pronounced temperature dependence. On the
      microscopic scale, the sustained caging effect leads to a separation between a
      faster in-cage relaxation component and a slower cage-breaking relaxation
      component. The evidence for the separate dynamic components, as opposed to a
      single stretched component, is provided by quasielastic neutron scattering
      experiments. We use a simple method to evaluate the extent of the dynamic
      components separation as a function of temperature in a group of related aromatic
      molecular liquids. We find that, regardless of the glass-forming capabilities or
      lack thereof, progressively more pronounced separation between the in-cage and
      cage-breaking dynamic components develops on cooling down as the ratio of T(b)/T,
      where T(b) is the boiling temperature, increases. This reflects the microscopic
      mechanism behind the empirical rule for the glass forming capability based on the
      ratio of boiling and melting temperatures, T(b)/T(m). When a liquid's T(b)/T(m)
      happens to be high, the liquid can readily be supercooled below its T(m) because
      the liquid's microscopic relaxation dynamics is already impeded at T(m), as
      evidenced by a sustained caging effect manifested through the separation of the
      in-cage and cage-breaking dynamic components. Our findings suggest certain
      universality in the temperature dependence of the microscopic diffusion dynamics
      in molecular liquids, regardless of their glass-forming capabilities. Unless the
      insufficiently low (with respect to T(b)) melting temperature, T(m), intervenes
      and makes crystallization thermodynamically favorable when cage-breaking is still
      unimpeded and the structural relaxation is fast, the liquid is likely to become
      supercooled. The propensity to supercooling and eventually forming a glass is
      thus determined by a purely thermodynamic factor, T(b)/T(m).

PMID- 23869490
TI  - Effects of growth form and functional traits on response of woody plants to
      clearing and fragmentation of subtropical rainforest.
AB  - The conservation implications of large-scale rainforest clearing and
      fragmentation on the persistence of functional and taxonomic diversity remain
      poorly understood. If traits represent adaptive strategies of plant species to
      particular circumstances, the expectation is that the effect of forest clearing
      and fragmentation will be affected by species functional traits, particularly
      those related to dispersal. We used species occurrence data for woody plants in
      46 rainforest patches across 75,000 ha largely cleared of forest by the early
      1900s to determine the combined effects of area reduction, fragmentation, and
      patch size on the taxonomic structure and functional diversity of subtropical
      rainforest. We compiled species trait values for leaf area, seed dry mass, wood
      density, and maximum height and calculated species niche breadths. Taxonomic
      structure, trait values (means, ranges), and the functional diversity of
      assemblages of climbing and free-standing plants in remnant patches were
      quantified. Larger rainforest patches had higher species richness. Species in
      smaller patches were taxonomically less related than species in larger patches.
      Free-standing plants had a high percentage of frugivore dispersed seeds; climbers
      had a high proportion of small wind-dispersed seeds. Connections between the
      patchy spatial distribution of free-standing species, larger seed sizes, and
      dispersal syndrome were weak. Assemblages of free-standing plants in patches
      showed more taxonomic and spatial structuring than climbing plants. Smaller
      isolated patches retained relatively high functional diversity and similar
      taxonomic structure to larger tracts of forest despite lower species richness.
      The response of woody plants to clearing and fragmentation of subtropical
      rainforest differed between climbers and slow-growing mature-phase forest trees
      but not between climbers and pioneer trees. Quantifying taxonomic structure and
      functional diversity provides an improved basis for conservation planning and
      management by elucidating the effects of forest-area reduction and fragmentation.
      Efectos de la Forma de Crecimiento y Atributos Funcionales en la Respuesta de
      Plantas Lenosas al Desmonte y Fragmentacion de Bosque Lluvioso Subtropical. 

PMID- 23869491
TI  - Recent advances in understanding the molecular pathogenesis of myelodysplastic
      syndromes.
AB  - The advent of novel genomic sequencing technologies has aided the identification
      of somatically acquired genetic abnormalities up to 80% of myelodysplastic
      syndrome (MDS) patients. Novel recurrent genetic mutations in pathways such as
      RNA splicing, DNA methylation and histone modification and cohesion complexes,
      underscore the molecular heterogeneity seen in this clinically varied disease.
      Functional studies to establish a causative link between genomic aberrations and
      MDS biogenesis are still in their infancy. The deluge of this molecular
      information, once validated on a larger cohort, will be incorporated into
      prognostic systems and clinical practise, and also hopefully aid in MDS
      therapeutics, especially in guiding targeted therapy. 

PMID- 23869492
TI  - Enalapril versus losartan for adults with chronic kidney disease: a systematic
      review and meta-analysis.
AB  - AIM: Both enalapril and losartan are effective and widely used in patients with
      chronic kidney disease (CKD). This review aimed to evaluate the benefits of
      enalapril and losartan in adults with CKD. METHODS: PubMed, EMBASE, the Cochrane
      Library and ClinicalTrials.gov were searched, without language limitations, for
      randomized controlled trials (RCT), in which enalapril and losartan were compared
      in adults with CKD. Standard methods, consistent with the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used.
      Reviewer Manager software, ver. 5.2, was used for meta-analysis. RESULTS: Of 318
      citations retrieved, 17 RCT (14 parallel-group and three cross-over) met our
      inclusion criteria. The pooled analysis for parallel RCT showed that the effects
      of enalapril and losartan on blood pressure, renal function and serum uric acid
      (UA) were similar. Meta-analysis indicated that patients taking enalapril had a
      higher risk of dry cough (risk ratio, 2.88; 95% CI, 1.11-7.48; P=0.03).
      Sensitivity analysis showed good robustness of these findings. CONCLUSION:
      Enalapril has similar effects to losartan on systemic blood pressure, renal
      function and serum UA in patients with CKD, but carries a higher risk of dry
      cough. Larger trials are required to evaluate the effects of these medications on
      clinical outcomes.

PMID- 23869494
TI  - Plasmonically nanoconfined light probing invisible phonon modes in defect-free
      graphene.
AB  - We present a simple plasmonic method that enables tuning of accessibility to the
      dipole-forbidden transition states of matter. This technique is realized by well
      controlled plasmonic dimers, which can confine optical fields on the order of
      molecular dimensions. As an example, the approach is applied to activate
      invisible noncenter phonon modes of defect-free graphene in resonance Raman
      spectra. The relative intensity of the normally forbidden modes with respect to
      the dipole allowed modes progressively increases as the degree of field
      confinement increases. This opens up a novel avenue for both photochemical
      excitation of molecular systems and nanoscale characterization of materials. 

PMID- 23869493
TI  - Quantitative analysis of microscopic X-ray computed tomography imaging: Japanese
      quail embryonic soft tissues with iodine staining.
AB  - Rapid three-dimensional imaging of embryos to better understand the complex
      process of morphogenesis has been challenging. Recently introduced iodine
      staining protocols (I2 KI and alcoholic iodine stains) combined with microscopic
      X-ray computed tomography allows visualization of soft tissues in diverse small
      organisms and tissue specimens. I2 KI protocols have been developed specifically
      for small animals, with a limited number of quantitative studies of soft tissue
      contrasts. To take full advantage of the low X-ray attenuation of ethanol and
      retain bound iodine while dehydrating the specimen in ethanol, we developed an
      ethanol I2 KI protocol. We present comparative microscopic X-ray computed
      tomography analyses of ethanol I2 KI and I2 KI staining protocols to assess the
      performance of this new protocol to visualize soft tissue anatomy in late stage
      Japanese quail embryos using quantitative measurements of soft tissue contrasts
      and sample shrinkage. Both protocols had only 5% shrinkage compared with the
      original harvested specimen, supporting the use of whole mounts to minimize
      tissue shrinkage effects. Discrimination within and among the selected organs
      with each staining protocol and microscopic X-ray computed tomography imaging
      were comparable to those of a gray scale histological section. Tissue
      discrimination was assessed using calibrated computed tomography values and a new
      discrimination index to quantify the degree of computed tomography value overlaps
      between selected soft tissue regions. Tissue contrasts were dependent on the
      depth of the tissue within the embryos before the embryos were saturated with
      each stain solution, and optimal stain saturations for the entire embryo were
      achieved at 14 and 28 days staining for I2 KI and ethanol I2 KI, respectively.
      Ethanol I2 KI provided superior soft tissue contrasts by reducing overstaining of
      fluid-filled spaces and differentially modulating staining of some tissues, such
      as bronchial and esophageal walls and spinal cord. Delineating the selected soft
      tissues using optimal threshold ranges derived from the quantitative analyses of
      the contrast enhancement in optimally stained embryos is possible. The protocols
      presented here are expected to be applicable to other organisms with
      modifications to staining time and contribute toward rapid and more efficient
      segmentation of soft tissues for three-dimensional visualization. 

PMID- 23869495
TI  - Effect of dietary carbohydrate, fat, and protein on postprandial glycemia and
      energy intake in cats.
AB  - BACKGROUND: Reducing carbohydrate intake is recommended in diabetic cats and
      might also be useful in some healthy cats to decrease diabetes risk. OBJECTIVE:
      To compare postprandial glucose and insulin concentrations and energy intakes
      between cats fed diets high in protein, fat, or carbohydrate. ANIMALS: Twenty
      four lean cats with normal glucose tolerance. METHODS: In a prospective
      randomized study, each of 3 matched groups (n = 8) received a different test diet
      for 5 weeks. Diets were high in either protein (46% of metabolizable energy
      [ME]), fat (47% ME), or carbohydrate (47% ME). Glucose and insulin were measured
      during glucose tolerance, ad libitum, and meal-feeding tests. RESULTS: During ad
      libitum feeding, cats fed the high-carbohydrate diet consumed 25% and 18% more
      carbohydrate than cats fed diets high in fat and protein, respectively, and
      energy intake was highest when the high-fat and high-protein diets were fed.
      Regardless of the feeding pattern, cats fed the high-carbohydrate diet had 10-31%
      higher peak and mean glucose compared with both other diets; peak glucose in some
      cats reached 10.4 mmol/L (188 mg/dL) in cats fed 47% ME carbohydrate and 9.0
      mmol/L (162 mg/dL) in cats fed 23% ME. CONCLUSIONS AND CLINICAL IMPORTANCE: High
      carbohydrate diets increase postprandial glycemia in healthy cats compared with
      diets high in fat or protein, although energy intake is lower. Avoidance of high-
      and moderate-carbohydrate diets can be advantageous in cats at risk of diabetes.
      Maintenance energy requirements should be fed to prevent weight gain when
      switching to lower carbohydrate diets.

PMID- 23869496
TI  - Fast in situ airborne measurement of ammonia using a mid-infrared off-axis ICOS
      spectrometer.
AB  - A new ammonia (NH3) analyzer was developed based on off-axis integrated cavity
      output spectroscopy. Its feasibility was demonstrated by making tropospheric
      measurements in flights aboard the Department of Energy Gulfstream-1 aircraft.
      The ammonia analyzer consists of an optical cell, quantum-cascade laser, gas
      sampling system, control and data acquisition electronics, and analysis software.
      The NH3 mixing ratio is determined from high-resolution absorption spectra
      obtained by tuning the laser wavelength over the NH3 fundamental vibration band
      near 9.67 MUm. Excellent linearity is obtained over a wide dynamic range (0-101
      ppbv) with a response rate (1/e) of 2 Hz and a precision of +/-90 pptv (1sigma in
      1 s). Two research flights were conducted over the Yakima Valley in Washington
      State. In the first flight, the ammonia analyzer was used to identify signatures
      of livestock from local dairy farms with high vertical and spatial resolution
      under low wind and calm atmospheric conditions. In the second flight, the
      analyzer captured livestock emission signals under windy conditions. Our results
      demonstrate that this new ammonia spectrometer is capable of providing fast,
      precise, and accurate in situ observations of ammonia aboard airborne platforms
      to advance our understanding of atmospheric compositions and aerosol formation. 

PMID- 23869497
TI  - Editorial: new graduate nursing unemployment: a threat to the future health care
      workforce.

PMID- 23869498
TI  - Relationship between nursing staffing and quality of life in nursing homes.
AB  - PURPOSE: To investigate the relationship between nurse staffing and quality of
      life in nursing homes. METHODS: This is a descriptive, correlational study. The
      independent variables were nursing staffing hours per resident day (HPRD), skill
      mix HPRD, and turnover rate of nursing staff. The data for the dependent
      variables were collected using the quality of life (QOL) section of minimum data
      set (MDS) version 3.0. Hierarchical linear models were used for data analysis.
      RESULTS: Few staffing variables were statistically associated with residents'
      QOL. More RN HPRD were associated with better comfort and enjoyment domains, more
      licensed practical nurses (LPN) HPRD were associated with better dignity, and
      more certified nurse assistant (CNA) HPRD were associated with better functional
      competence domains. In terms of skill mix, the unique contribution of more RNs
      (to less LPN or CNAs) was supported in the functional competence of residents.
      However, surprising results were that: (a) as the HPRD of RNs increased, the
      scores of meaningful activity and relationship decreased; and (b) the
      contribution of LPNs (more LPNs to less RNs) were supported in the autonomy and
      spiritual well-being domains. Interestingly, nursing staff turnover is positively
      correlated with some domains of QOL: (a) a higher score in the enjoyment domain
      with increased RN turnover; and (b) a higher score in privacy, relationship, and
      individuality domains with increased turnover of LPNs. CONCLUSION: This is a
      preliminary study to investigate the relationship between nursing staffing and
      QOL for nursing home residents. Further examination is needed to confirm the
      relationship and provide policy guidelines, including nurse staffing
      recommendations.

PMID- 23869499
TI  - Increasing sharp safety device use in healthcare: a semi-structured interview
      study.
AB  - The use of sharp safety devices in healthcare is considered the most important
      means of preventing occupational percutaneous injuries and has been mandated for
      use in most hospitals in industrialized countries including in Canada. However,
      clinical personnel's perceptions on the use of safety devices needs further
      characterization to improve compliance. This study's objective was to identify
      healthcare provider perspectives on different aspects of sharp safety device use
      and on how use could be increased. Using a constant comparison approach, data
      from semi-structured interviews with 39 nurses, physicians and phlebotomists
      providing direct patient care, and six nurses acting as the interface between
      clinical personnel and purchasing departments, were analyzed. Study participants
      were from three of the six health authorities in British Columbia. The four major
      categories that emerged from the data were: selection processes; identification
      and replacement; training; and multi-level barriers and facilitators. Findings
      highlighted the importance of including personnel regularly using safety devices
      at each stage of their selection including when they are being considered for
      replacement with superior devices, as well as the need for appropriate initial
      and refresher training, and how practices at the hospital, ward and individual
      level facilitate safety device use.

PMID- 23869500
TI  - Care planning practices for behavioural and psychological symptoms of dementia in
      residential aged care: a pilot of an education toolkit informed by the Aged Care
      Funding Instrument.
AB  - AIM: To assess the feasibility and the effects of a multi-component education
      toolkit that used the Aged Care Funding Instrument behaviour (ACFI-BEH) scores to
      trigger care planning for older people experiencing behavioural and psychological
      symptoms of dementia (BPSD). METHOD: Forty-six older people and 209 staff and
      managers from five Sydney metropolitan residential aged care (RAC) facilities
      participated in this pre-post intervention pilot study. RESULTS: The face
      validity and accessibility/acceptability of the toolkit was established, but
      potential utility of the ACFI-BEH in informing care planning was proven to be
      negligible. The ACFI-informed education toolkit did not lead to statistically
      significant improvements in care planning practice or reduce the
      severity/frequency of the targetted BPSD. Care plan quality remained low post
      intervention, with between 31% (N = 12/39) and 65% (N = 13/20) of care plans not
      addressing the persons' BPSD, nor utilising the ACFI information in relation to
      BPSD. CONCLUSION: This study has underscored the problems associated with current
      care planning practice in RAC settings and the need for developing strategies to
      ensure quality and safe care through individualised care planning practices. Our
      study processes, results and lessons discussed in this paper could assist future
      research on this type of research in RAC settings.

PMID- 23869501
TI  - Lessons students and new graduates could teach: a phenomenological study that
      reveals insights on the essence of building a supportive learning culture through
      preceptorship.
AB  - Nursing educators engage in many practices and one of the most important is
      preceptorship. However, evidence underpinning preceptorship is scant. Indeed some
      critics suggest that the planning, delivery and evaluation of preceptorship
      programmes rarely involves the people they are designed to assist - namely
      students. This qualitative study, part of a larger phenomenology of the
      experience of students and new graduates, included the exploration and
      description of students' experiences of preceptorship. Thirteen undergraduate
      Bachelor of Nursing students aged 20-50 years participated in semi-structured
      interviews. Data were collected at three intervals; prior to commencing
      employment as graduate nurses, 1 and 6 months post-employment. Five key themes
      were revealed: confidence; friendship; being thrown in at the deep end; peer
      support; and lack of support. Application of the findings from this research may
      help to improve the preceptorship experience for future students and new
      graduates and to inform evidence-based preceptorship preparation.

PMID- 23869502
TI  - Enhancing transformational facilitation skills for nurses seeking to support
      practice innovation.
AB  - AIMS: To provide an overview of the development, implementation and process
      evaluation of a programme for nurses seeking to develop the knowledge and skills
      required to facilitate practice innovation. METHOD: The 12 month facilitation in
      clinical practice programme was underpinned by transformational practice
      development (tPD) methodology. The programme included a series of workshops,
      active learning groups and was supported by experienced facilitators, using a co
      facilitation model. Evaluation occurred continuously throughout the programme.
      RESULTS: Participants evaluated the programme positively and were able to apply
      their evolving knowledge and skills within their everyday practice. Their major
      areas of learning included active participation in their own learning, an
      increased valuing of diversity within the group and application of their learning
      in facilitation of practice development initiatives. The co-facilitation model
      was found to challenge and support ongoing development of the facilitators.
      CONCLUSIONS: Participation in the facilitation in clinical practice programme
      enhances nurses' knowledge and skills for undertaking tPD.

PMID- 23869504
TI  - Obtaining higher research degree qualifications: key strategies to consider.
AB  - The literature describing the experience of nurses undertaking higher studies
      suggests that many students struggle with the demands of study and other aspects
      of their lives, such as work and family commitments. The aim of this paper is to
      encourage higher degree students to develop a strategic approach to their studies
      in order that they: (1) minimize the extra demands created by additional studies;
      and (2) make the most of their work as a student to facilitate the development of
      their careers and establish a track record in doing so. We also provide an
      overview of relevant issues to consider, including Thesis marking and discuss
      some of the practicalities to make the most of higher degree opportunities.

PMID- 23869503
TI  - Survey of attitudes of nurses and junior doctors to co-management of high risk
      surgical patients.
AB  - Managing post-operative surgical patients can be complex, with many patients at
      risk of complications and mortality. We piloted a model for co-management of high
      risk surgical patients: the post-operative surveillance team (POST). We conducted
      a survey to test the proposition that POST would be popular with nurses and
      junior doctors. We conducted a questionnaire survey of nurses and doctors
      involved with the POST programme. Fifty-three nurses and 10 doctors responded to
      the survey: 60% response rate. Of 63 respondents: 62 (98%; 95% CI: 92-100%)
      agreed that POST was valuable, 61 (97%; 95% CI: 89-99%) agreed that POST should
      continue, and 61 (97%; 95% CI: 89-99%) agreed that they enjoyed working with
      POST. In open ended responses 39% commented that POST provided supervision,
      mentoring, education, or collaboration. We conclude that POST was popular with
      surgical ward nurses and doctors. This popularity is one factor supporting a
      permanent service.

PMID- 23869505
TI  - Barriers to education in cardiac rehabilitation within an Iranian society: a
      qualitative descriptive study.
AB  - INTRODUCTION: Cardiac rehabilitation programmes that include patient education
      aim to maximise physical, psychological and social functioning, and enable people
      with acute coronary syndrome to lead fulfilling and productive lives. Despite
      strong evidence for the benefits of patient education, various barriers exist
      that need to be addressed to ensure the effective delivery of care. This study
      explores patients/family members and health professionals' perceptions and
      experiences of the barriers to cardiac rehabilitation education in an Iranian
      context. METHODS: A thematic analysis of in-depth interviews was undertaken using
      a constant comparative approach. Participants (10 health professionals, 15
      patients/family members) were recruited from educational-medical centers and
      hospitals in Iran. Credibility and trustworthiness were grounded on four aspects:
      factual value, applicability, consistency and neutrality. RESULTS: Five major
      barriers to cardiac rehabilitation were identified relating to human resources,
      service provision, available educational services, unfavourable attitudes and
      collaboration gaps. Two main challenges exist to the provision of effective
      patient education; inadequate human resources in the hospital wards, specifically
      in terms of trained health care professionals and service users specific health
      related views and behaviours. CONCLUSION: Barriers to comprehensive patient
      education and cardiac rehabilitation in Iran must be addressed and urgent
      consideration should be given to the introduction and evaluation of education
      programmes to prepare health/support system professionals as well as service
      users, and cardiac rehabilitation services that employ a collaborative and
      individualised approach. This in turn may reduce the burden of CVD and improve
      the overall health and quality of life for people in Isfahan Iran.

PMID- 23869506
TI  - Clinical indicators of 'caregiver role strain' in caregivers of stroke patients.
AB  - The main objectives of this study were to investigate the prevalence of the
      nursing diagnosis caregiver role strain (CRS) in caregivers of patients with
      stroke and to identify the accuracy of this diagnosis's clinical indicators. A
      total of 42 stroke patient caregivers who provided in-home care services in a
      city in north-eastern Brazil. The sensitivity, specificity, and predictive value
      of clinical indicators of nursing diagnosis 'CRS' were analyzed. Study
      participants were mostly female, married and the daughters of stroke patients.
      CRS was present in 73.8% of caregivers. The presence of the clinical indicators,
      specifically, lack of time to meet personal needs (p = 0.011), increased
      emotional lability (p = 0.001), withdrawal from social life (p = 0.002), and
      changes in leisure activities (p = 0.002), presented high values for statistical
      measures of diagnostic accuracy.

PMID- 23869507
TI  - The wartime experience of civilian nurses in Iran-Iraq war, 1980-1988: an
      historical research.
AB  - BACKGROUND: During the 8 years of Iran-Iraq war, the work of Iranian nurses was
      essential and efficiently performed, and played a very important role in
      maintaining the wellbeing of the forces. A review of nurses' activities reveals
      their experiences and the nature of their activities, an area of study that has
      not been given due consideration. METHOD: By adopting the oral history method and
      in-depth interviews with the participating nurses it was possible to demonstrate
      the significance and humanistic nature of their work. FINDINGS: The majority of
      the health care assistants and nurses who joined the armed forces, despite not
      having prior training in this area of nursing, were able to adapt themselves to
      the situation very quickly and perform their task successfully. CONCLUSION:
      Nurses' efforts and experiences and their outstanding achievement, contributes to
      our understanding of wartime nursing.

PMID- 23869508
TI  - Exploring nursing students' understanding of being regulated.
AB  - In Australia, a national approach to the regulation of health practitioners and
      students has been established through the Health Practitioner Regulation National
      Law Act (2009; Qld) (the National Act). Whilst regulation of nursing and
      midwifery students under this new scheme is novel in most jurisdictions, students
      in South Australia have been registered with the Nursing and Midwifery Board of
      South Australia under the Nursing and Midwifery Practice Act 2008 (SA) (the State
      Act) since January 2010. Given the significant move to national registration of
      nursing and midwifery students, a mixed method study was initiated exploring
      South Australian nursing students' understanding of being regulated. Two hundred
      and twenty online surveys were completed and four focus groups conducted.
      Analysis revealed participants had little understanding of regulation and how the
      State Act applied to their student role and practice. The study recommends a
      nationally consistent strategy to inform students of their regulatory
      responsibilities.

PMID- 23869509
TI  - Exploring the ethos of district nursing, 1885-1985.
AB  - The history of district nursing in Australia explored in this paper reveals a
      continuity in the essential values held by district nurses for over a century.
      These nurses practised holistic, family-centred nursing from the very origins of
      district nursing service. The events surrounding the establishment of Community
      Health Centres in the 1970s challenged district nurses to reconsider their role,
      while at the same time reconfirming their essential ethos. These values that
      underpinned district nursing practice and challenges to these values are examined
      in this paper.

PMID- 23869510
TI  - Commentary: negative workplace behaviours at the University of Hard Knocks.

PMID- 23869511
TI  - Syphilis related to atypical oral lesions affecting an elderly man. a case
      report.
AB  - OBJECTIVE: To present a case of oral syphilis in an old patient. BACKGROUND:
      Syphilis seems to be resurging mainly in the young. However, in the last twenty
      years, the elderly have become more susceptive to infectious diseases due to a
      more frequent use of sildenafil. CLINICAL REPORT: An 83-year-old man was referred
      to our clinic complaining of burning mouth. His medical history revealed papular
      lesions on chest and penis glans, which had been diagnosed and treated as
      scabiosis 2 months prior to our assessment. The intra-oral examination showed
      erosive and patch lesions on the bilateral lip commissures, the palate and the
      border of the tongue. Initially, oral herpes was suspected. However, both the
      serological test and the cytology were negative. Therefore, syphilis was
      hypothesised. Non-treponemic (VDRL) and treponemic tests (FTA-ABS) were reagent
      and secondary syphilis was confirmed. The treatment consisted of penicillin G
      benzathine 2.4 million IU/IM for 4 weeks. Both oral and skin lesions had complete
      remission. CONCLUSION: The present case illustrates that syphilis should be
      suspected in old patients with oral atypical lesions.

PMID- 23869512
TI  - Management of infants born with severe neonatal alloimmune thrombocytopenia: the
      role of platelet transfusions and intravenous immunoglobulin.
AB  - BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a fetomaternal
      incompatibility most commonly induced by maternal anti-HPA-1a alloantibodies.
      Transfusion of immunologically compatible platelets (PLTs) to prevent cerebral
      hemorrhage, the most severe complication in affected newborns, is usually
      recommended. Such PLT concentrates, however, are often not readily available.
      STUDY DESIGN AND METHODS: The efficacy of random-donor PLT transfusions and
      intravenous immunoglobulin (IVIG) for the management of 17 neonates across four
      centers with unexpected, severe NAIT was evaluated. Neonates were treated with
      random-donor PLTs alone (n=7), random-donor PLTs with IVIG (n=8), or matched HPA
      1bb PLTs (n=2). RESULTS: All but one patient (treated with random PLTs and IVIG)
      achieved a posttransfusion PLT count of higher than 30 * 10(9) /L after the first
      PLT transfusion. The PLT count remained higher than 30 * 10(9) /L for longer than
      24 hours in five of seven, seven of eight, and two of four newborns who received
      random-donor PLTs alone, random-donor PLTs with IVIG, or matched HPA-1bb PLTs,
      respectively. None of the newborns developed major bleeding or intracranial
      hemorrhage. IVIG did not appear to improve either posttransfusion PLT counts or
      total PLT transfusion requirements. CONCLUSION: Transfusion of random-donor PLTs
      alone was effective at correcting critically low PLT counts and should be
      considered as first-line treatment of newborns with unexpected severe NAIT.

PMID- 23869513
TI  - A new protopanaxadiol-type ginsenoside from the roots of Panax notoginseng.
AB  - A new protopanaxadiol-type ginsenoside, 6-O-beta-d-glucopyranosyl-20-O-beta-d
      glucopyranosyl-20(S)-protopanaxadiol-3-one (1), along with three known compounds,
      was isolated from the roots of Panax notoginseng. Their structures were
      determined based on some pieces of spectroscopic and chemical evidence. Compound
      1 exhibited cytotoxic activity against five human cancer cell lines, with IC50
      values ranging from 5.4 to 8.6 MUg/ml. 

PMID- 23869515
TI  - A comparison of methodologies of brief functional analysis.
AB  - OBJECTIVE: To evaluate correspondence between three models of brief functional
      analysis (BFA); to evaluate a latency-based model of BFA. METHODS: Single subject
      research; three models of BFA; latency-based BFA; brief A-B model with programmed
      antecedents and no programmed consequences for aberrant behaviour; A-B-C model
      with programmed antecedents and programmed consequences for aberrant behaviour;
      contingency reversal treatment evaluations conducted with each model; each model
      implemented with four individuals with autism diagnoses; correspondence of
      results between the three BFA models in terms of the conditions in which aberrant
      behaviour occurred. RESULTS: Overall, strong correspondence between all three BFA
      models was observed; several specific instances of non-correspondence within
      participants observed; more differentiation observed between test and control
      conditions in A-B model than A-B-C model. CONCLUSIONS: Additional support that
      clinicians and educators have flexibility in choosing BFA model that fits the
      specific, idiosyncratic variables and constraints of their setting (e.g.
      outpatient; classroom) and client(s).

PMID- 23869514
TI  - Perioperative blood transfusion affects hepatitis C virus (HCV)-specific immune
      responses and outcome following liver transplantation in HCV-infected patients.
AB  - OBJECTIVES: Perioperative factors can affect outcomes of liver transplantation
      (LT) in recipients with hepatitis C virus (HCV) infection. This study was
      conducted to investigate whether the immunomodulatory effects of packed red blood
      cells (PRBC) and platelets administered in the perioperative period might affect
      immune responses to HCV and thus outcomes in LT recipients. METHODS: Data for a
      total of 257 HCV LT recipients were analysed. Data on clinical demographics
      including perioperative transfusion (during and within the first 24 h), serum
      cytokine concentration, HCV-specific interferon-gamma (IFN-gamma) and interleukin
      17 (IL-17) producing cells, and outcomes including graft and patient survival
      were analysed. RESULTS: Patient survival was higher in HCV LT recipients who did
      not receive transfusions (Group 1, n = 65) than in those who did (Group 2, n =
      192). One-year patient survival was 95% in Group 1 and 88% in Group 2 (P = 0.02);
      5-year survival was 77% in Group 1 and 66% in Group 2 (P = 0.05). Group 2 had an
      increased post-transplant viral load (P = 0.032) and increased incidence of
      advanced fibrosis at 1 year (P = 0.04). After LT, Group 2 showed increased IL-10,
      IL-17, IL-1beta and IL-6, and decreased IFN-gamma, and a significantly increased
      rate of IL-17 production against HCV antigen. Increasing donor age (P = 0.02),
      PRBC transfusion (P < 0.01) and platelets administration were associated with
      worse survival. CONCLUSIONS: Transfusion had a negative impact on LT recipients
      with HCV. The associated early increase in pro-HCV IL-17 and IL-6, with decreased
      IFN-gamma, suggests that transfusion may be associated with the modulation of HCV
      specific responses, increased fibrosis and poor transplant outcomes.

PMID- 23869516
TI  - Health and well-being among physicians.
AB  - BACKGROUND AND AIM: Physicians' attitudes towards disease prevention are crucial.
      The purposes of this study are to examine the prevalence of cardiovascular risk
      factors and adherence to international preventive screening programmes by a group
      of physicians. METHODS: Online and paper format questionnaires were completed by
      a sample of 650 physicians from November 2010 to March 2011. The collected data
      included the main components of screening programmes, which are recommended in
      international guidelines. RESULTS: The data show that 30.5% of male physicians
      currently smoke, 19.4 % are obese, 15.2% have hypertension, 38% are physically
      inactive and 10.9% have diabetes. Nearly all (95%) of the female participants and
      most (83%) of the male participants older than 45 years had never had a
      colonoscopy. Of the male physicians older than 55 years, 36.4% had never had
      prostate-specific antigen testing, and only 10.9% had undergone a digital rectal
      examination. Among the female physicians, 27.4% were obese, and 42% had never had
      a mammogram. CONCLUSION: The prevalence of behavioural risk factors for
      cardiovascular disease is high among physicians. A substantial percentage of the
      practising physicians did not adhere to the age-specified preventive screening
      measures recommended in international guidelines.

PMID- 23869517
TI  - Doing the right thing for health.

PMID- 23869518
TI  - A prospective, randomized controlled trial of circumcision in adult males using
      the CO2 laser: modified technique compared with the conventional dorsal-slit
      technique.
AB  - OBJECTIVE: The purpose of this study was to investigate the safety and efficacy
      of a modified CO2 laser technique for circumcision in adult males as compared
      with the conventional dorsal-slit method. BACKGROUND DATA: Circumcision is one of
      the most commonly performed surgeries in the world. Although present techniques
      produce a good long-term result, there is a continuing need to improve the safety
      and efficacy of the circumcision procedure. MATERIALS AND METHODS: Data were
      analyzed from a prospective randomized controlled clinical study comparing two
      different operative techniques for adult circumcision: the modified CO2 laser
      circumcision technique, and the conventional dorsal-slit technique. A total of
      300 patients >18 years of age were recruited in this study. Several perioperative
      data, including age, indications, operation time, intraoperative blood loss,
      complications, and postoperative pain were analyzed. Differences between the CO2
      laser technique and the conventional technique were compared. RESULTS: There was
      no statistically significant difference in age distribution and indications
      between the two groups. Compared with the conventional group, there were shorter
      operative time, less blood loss and lower postoperative complication rate in the
      laser group. The CO2 laser technique was associated with much less pain, as
      quantitated by a 10 point visual analogue scale (VAS) pain score at both 1 day
      and 7 days postoperatively. CONCLUSIONS: The modified CO2 laser technique that we
      introduced offers a simple, safe, faster, and effective alternative method to the
      conventional technique in adult male circumcision, with decreased blood loss,
      pain, and complications.

PMID- 23869519
TI  - Experimental study to understand nonspecific protoporphyrin IX fluorescence in
      brain tissues near tumors after 5-aminolevulinic acid administration.
AB  - OBJECTIVE: (PpIX) fluorescence induced by 5-aminolevulinic acid (5-ALA), which
      appears in various tumors including malignant gliomas, is a good navigator for
      tumor resection. However, some non-neoplastic tissue also shows a weak PpIX
      fluorescence. The origin of non-neoplastic PpIX is still unknown, and three
      hypotheses on its origins can be proposed: tumor cell-derived PpIX followed by
      dispersal via bulk flow, direct PpIX production by normal brain or gliotic brain
      tissue, or PpIX produced in other organs leaking from the tumor vessels. We
      investigated the possibility of these three origins experimentally. METHODS: In
      vitro, we exposed various cultured glioma and meningioma cell lines to different
      conditions of 5-ALA. After this, the degree of fluorescence of the culture medium
      and cells was each quantitatively measured and analyzed by means of photometrical
      assay. We administered 5-ALA directly into the normal brains of rats by using
      convection-enhanced delivery technique, and we also administered 5-ALA or PpIX
      systemically after blood-brain barrier (BBB) disruption. RESULTS: As a result of
      our in vitro study using cell lines, we found fluorescence of extracellular PpIX
      in the culture medium. As a result of rat study, we found PpIX fluorescence of
      the extracted normal brain after systemic administration of 5-ALA with BBB
      disruption. However, no PpIX fluorescence was observed when we administered PpIX.
      CONCLUSIONS: It was demonstrated that PpIX was quickly excreted by tumor cells
      out to the extracellular space, and that even normal brain tissue can produce
      PpIX in the presence of 5-ALA.

PMID- 23869520
TI  - Validation of potential inhibitors for SrtA against Bacillus anthracis by
      combined approach of ligand-based and molecular dynamics simulation.
AB  - The development of SrtA inhibitors targeting the biothreat organism namely
      Bacillus anthracis was achieved by the combined approach of pharmacophore
      modeling, binding interactions, electron transferring capacity, ADME, and
      Molecular dynamics studies. In this study, experimentally reported Ba-SrtA
      inhibitors (pyridazinone and pyrazolethione derivatives) were considered for the
      development of enhanced pharmacophoric model. The obtained AAAHR hypothesis was a
      pure theoretical concept that accounts for common molecular interaction network
      present in experimentally active pyridazinone and pyrazolethione derivatives.
      Pharmacophore-based screening of AAAHR hypothesis provides several new compounds,
      and those compounds were treated with four phases of docking protocols with
      combined Glide-QPLD docking approach. In this approach, scoring and charge
      accuracy variations were seen to be dominated by QM/MM approach through the
      allocation of partial charges. Finally, we reported the best compounds from
      binding db, Chembridge db, and Toslab based on scoring values, energy parameters,
      electron transfer reaction, ADME, and cell adhesion inhibition activity. The
      dynamic state of interaction and binding energy assess that new compounds are
      more active inside the binding pocket and these compounds on experimental
      validations will survive as better inhibitors for targeting the cell adhesion
      mechanism of Ba-SrtA. 

PMID- 23869521
TI  - Cereblon expression in multiple myeloma: not ready for prime time - response to
      Lode et al.

PMID- 23869523
TI  - Computational infrared and two-dimensional infrared photon echo spectroscopy of
      both wild-type and double mutant myoglobin-CO proteins.
AB  - The CO stretching mode of both wild-type and double mutant ( T67R / S92D ) MbCO
      (carbonmonoxymyoglobin) proteins is an ideal infrared (IR) probe for studying the
      local electrostatic environment inside the myoglobin heme pocket. Recently, to
      elucidate the conformational switching dynamics between two distinguishable
      states, extensive IR absorption, IR pump-probe, and two-dimensional (2D) IR
      spectroscopic studies for various mutant MbCO's have been performed by the Fayer
      group. They showed that the 2D IR spectroscopy of the double mutant, which has a
      peroxidase enzyme activity, reveals a rapid chemical exchange between two
      distinct states, whereas that of the wild-type does not. Despite the fact that a
      few simulation studies on these systems were already performed and reported, such
      complicated experimental results have not been fully reproduced nor described in
      terms of conformational state-to-state transition processes. Here, we first
      develop a distributed vibrational solvatochromic charge model for describing the
      CO stretch frequency shift reflecting local electric potential changes. Then, by
      carrying out molecular dynamic simulations of the two MbCO's and examining their
      CO frequency trajectories, it becomes possible to identify a proper reaction
      coordinate consisting of His64 imidazole ring rotation and its distance to the CO
      ligand. From the 2D surfaces of the resulting potential of mean forces, the
      spectroscopically distinguished A1 and A3 states of the wild-type as well as two
      more substates of the double mutant are identified and their vibrational
      frequencies and distributions are separately examined. Our simulated IR
      absorption and 2D IR spectra of the two MbCO's are directly compared with the
      previous experimental results reported by the Fayer group. The chemical exchange
      rate constants extracted from the two-state kinetic analyses of the simulated 2D
      IR spectra are in excellent agreement with the experimental values. On the basis
      of the quantitative agreement between the simulated spectra and experimental
      ones, we further examine the conformational differences in the heme pockets of
      the two proteins and show that the double mutation, T67R / S92D , suppresses the
      A1 population, restricts the imidazole ring rotation, and increases hydrogen-bond
      strength between the imidazole Nepsilon-H and the oxygen atom of the CO ligand.
      It is believed that such delicate change of distal His64 imidazole ring dynamics
      induced by the double mutation may be responsible for its enhanced peroxidase
      catalytic activity as compared to the wild-type myoglobin. 

PMID- 23869522
TI  - Dendrimers terminated with dichlorotriazine groups provide a route to
      compositional diversity.
AB  - Triazine dendrimers terminated with either four or eight dichlorotriazines can be
      prepared in high yields by reacting an amine-terminated dendrimer with cyanuric
      chloride. These materials exist as white powders and are stable to storage at
      room temperature. Sequential nucleophilic aromatic substitution with two
      different amine nucleophiles yields compounds that display the desired
      compositional diversity. Reaction conditions for the substitution were developed
      using a model dichlorotriazine with amine nucleophiles at -20, 0, and 25  degrees
      C. Selective substitution is favored at lower temperatures and with more
      nucleophilic amine groups. 

PMID- 23869524
TI  - Electrochemically deposited Pd-Pt and Pd-Au codeposits on graphite electrodes for
      electrocatalytic H2O2 reduction.
AB  - Improved electrocatalytic activity and selectivity for the reduction of H2O2 were
      obtained by electrodepositing Pd-Pt and Pd-Au on spectrographic graphite from
      solutions containing salts of the two metals at varying ratio. The
      electrocatalytic activity of the resulting binary codeposits for H2O2 reduction
      was evaluated by means of the redox-competition mode of scanning electrochemical
      microscopy (SECM) and voltammetric methods. In a potential range from 0 to -600
      mV (vs. Ag/AgCl/3 M KCl) at pH 7.0 in 0.1 M phosphate citrate buffer, the
      electrocatalytic activity of both Pd-Pt and Pd-Au codeposits was substantially
      improved as compared with the identically deposited single metals suggesting an
      electrocatalytic synergy of the codeposits. Pd-Pt and Pd-Au codeposits were
      characterized by X-ray diffraction (XRD) analysis and scanning electron
      microscopy (SEM). Codepositing with Au caused a change of hedgehog-like shaped Pd
      nanoparticles into cauliflower-like nanoparticles with the particle size
      decreasing with increasing Au concentration. Codepositing Pd with Pt caused the
      formation of oblong structures with the size initially increasing with increasing
      Pt content. However, the particle size decreases with further increase in Pt
      concentration. The improved electrocatalytic capability for H2O2 reduction of the
      Pd-Pt electrodeposits on graphite was further demonstrated by immobilizing
      glucose oxidase as a basis for the development of an interference-free
      amperometric glucose biosensor. 

PMID- 23869525
TI  - Seven-year experience of enterocutaneous fistula with univariate and multivariate
      analysis of factors associated with healing: development of a validated scoring
      system.
AB  - AIM: The management of enterocutaneous fistulae (ECF) is complex and challenging.
      We examined factors associated with fistula healing at a National Intestinal
      Failure Centre and devised the first scoring system to predict spontaneous
      fistula healing prior to surgery. METHOD: A retrospective audit of 177 patients
      (mean age 48.7 years) treated over 7 years was undertaken. Results were compared
      with a previously reported series from this unit. Univariate and multivariate
      analyses wete performed on variables to assess relationship with ECF healing. A
      scoring system was devised and validated on a prospective cohort. RESULTS: One
      hundred and fifty patients underwent surgery between January 2003 and December
      2009. The overall healing rate following surgery in the current series was 94.6%
      (82% in the previous series). Mean delay from previous surgery to the current
      operation was 1 year (compared with 8 months previously). Thirty-day postfistula
      resection mortality was 0% (compared with 3.5% previously). Twenty-seven patients
      underwent medical management alone with overall healing rate of 46.4% (vs 19.9%).
      Multivariate analysis revealed that comorbidity (P = 0.02), source of referral (P
      = 0.01) and aetiology (P = 0.006) had associations with healing. Almost all
      patients with scores of 0 and 1 healed, whereas the highest scores healed least
      frequently. CONCLUSION: Surgical management of ECF is safe and improving. Fistula
      healing is affected by aetiology, comorbidity and source of referral. The scoring
      system has the potential to predict ECF healing and can be a useful clinical
      decision-making tool.

PMID- 23869526
TI  - Foraging and vulnerability traits modify predator-prey body mass allometry:
      freshwater macroinvertebrates as a case study.
AB  - 1. Predation is often size selective, but the role of other traits of the prey
      and predators in their interactions is little known. This hinders our
      understanding of the causal links between trophic interactions and the structure
      of animal communities. Better knowledge of trophic traits underlying predator
      prey interactions is also needed to improve models attempting to predict food web
      structure and dynamics from known species traits. 2. We carried out laboratory
      experiments with common freshwater macroinvertebrate predators (diving beetles,
      dragonfly and damselfly larvae and water bugs) and their prey to assess how body
      size and traits related to foraging (microhabitat use, feeding mode and foraging
      mode) and to prey vulnerability (microhabitat use, activity and escape behaviour)
      affect predation strength. 3. The underlying predator-prey body mass allometry
      characterizing mean prey size and total predation pressure was modified by
      feeding mode of the predators (suctorial or chewing). Suctorial predators fed
      upon larger prey and had ~3 times higher mass-specific predation rate than
      chewing predators of the same size and may thus have stronger effect on prey
      abundance. 4. Strength of individual trophic links, measured as mortality of the
      focal prey caused by the focal predator, was determined jointly by the predator
      and prey body mass and their foraging and vulnerability traits. In addition to
      the feeding mode, interactions between prey escape behaviour (slow or fast), prey
      activity (sedentary or active) and predator foraging mode (searching or ambush)
      strongly affected prey mortality. Searching predators was ineffective in
      capturing fast-escape prey in comparison with the remaining predator-prey
      combinations, while ambush predators caused higher mortality than searching
      predators and the difference was larger in active prey. 5. Our results imply that
      the inclusion of the commonly available qualitative data on foraging traits of
      predators and vulnerability traits of prey could substantially increase
      biological realism of food web descriptions.

PMID- 23869527
TI  - Practical recommendations to help students bridge the research-implementation gap
      and promote conservation.
AB  - Seasoned conservation researchers often struggle to bridge the research
      implementation gap and promote the translation of their work into meaningful
      conservation actions. Graduate students face the same problems and must contend
      with obstacles such as limited opportunities for relevant interdisciplinary
      training and a lack of institutional support for application of research results.
      However, students also have a crucial set of opportunities (e.g., access to
      academic resources outside their degree programs and opportunities to design
      research projects promoting collaboration with stakeholders) at their disposal to
      address these problems. On the basis of results of breakout discussions at a
      symposium on the human dimensions of the ocean, a review of the literature, and
      our own experiences, we devised recommendations on how graduate students can
      create resources within their academic institutions, institutionalize resources,
      and engage with stakeholders to promote real-world conservation outcomes. Within
      their academic institutions, graduate students should foster links to
      practitioners and promote knowledge and skill sharing among students. To
      institutionalize resources, students should cultivate student leaders and faculty
      sponsors, systematically document their program activities, and engage in
      strategic planning to promote the sustainability of their efforts. While
      conducting research, students should create connections to and engage actively
      with stakeholders in their relevant study areas and disseminate research results
      both to stakeholders and the broader public. Our recommendations can serve as a
      template for graduate students wishing to bridge the research-implementation gap,
      both during their current studies and in their future careers as conservation
      researchers and practitioners.

PMID- 23869528
TI  - Manganese-tin triple bonds: a new synthetic route to the manganese stannylidyne
      complex cation trans-[H(dmpe)2Mn=Sn(C6H3-2,6-Mes2)]+ (dmpe = Me2PCH2CH2PMe2, Mes
      = 2,4,6-trimethylphenyl).
AB  - A new approach to the first complex featuring a manganese-tin triple bond that
      takes advantage of the propensity of dihydrogen complexes to eliminate H2 is
      reported. Reaction of the 18-valence-electron manganese dihydrogen hydride
      complex [MnH(eta(2)-H2)(dmpe)2] (1) (dmpe = Me2PCH2CH2PMe2) with the
      organotin(II) chloride SnCl(C6H3-2,6-Mes2) (Mes = 2,4,6-trimethylphenyl)
      selectively afforded by H2 elimination the chlorostannylidene complex trans
      [H(dmpe)2Mn?Sn(Cl)(C6H3-2,6-Mes2)] (2), which upon treatment with Na[B(C6H3-3,5
      (CF3)2)4] and Li[Al(OC(CF3)3)4] was transformed quantitatively into the
      stannylidyne complex salts trans-[H(dmpe)2Mn=Sn(C6H3-2,6-Mes2)]A [A = B(C6H3-3,5
      (CF3)2)4 (3a), Al(OC(CF3)3)4 (3b)]. Complexes 2 and 3a/3b were fully
      characterized, and the structures of 2 and 3a were determined by single-crystal X
      ray diffraction. Complex 2 features the shortest Mn-Sn double bond reported to
      date, a large Mn-Sn-Caryl bond angle, and a long Sn-Cl bond of the trigonal
      planar-coordinated tin center. These bonding features can be rationalized in
      valence-bond terms by a strong contribution of the triply bonded resonance
      structure [LnMn=SnR]Cl and were verified by a natural resonance theory (NRT)
      analysis of the electron density of the DFT-minimized structure of 2. Complex 3a
      features the shortest Mn-Sn bond reported to date and a linearly coordinated tin
      atom. Natural bond order and NRT analyses of the electronic structure of the
      complex cation in 3a/3b suggested a highly polar Mn-Sn triple bond with a 65%
      ionic contribution to the NRT Mn-Sn bond order of 2.25. Complex 3a undergoes
      reversible one-electron reduction, suggesting that open-shell stannylidyne
      complexes might be accessible using strong reducing agents. 

PMID- 23869529
TI  - The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is
      important for maintaining normal blood-stage growth.
AB  - Plasmodium parasites remodel their vertebrate host cells by translocating
      hundreds of proteins across an encasing membrane into the host cell cytosol via a
      putative export machinery termed PTEX. Previously PTEX150, HSP101 and EXP2 have
      been shown to be bona fide members of PTEX. Here we validate that PTEX88 and TRX2
      are also genuine members of PTEX and provide evidence that expression of PTEX
      components are also expressed in early gametocytes, mosquito and liver stages,
      consistent with observations that protein export is not restricted to asexual
      stages. Although amenable to genetic tagging, HSP101, PTEX150, EXP2 and PTEX88
      could not be genetically deleted in Plasmodium berghei, in keeping with the
      obligatory role this complex is postulated to have in maintaining normal blood
      stage growth. In contrast, the putative thioredoxin-like protein TRX2 could be
      deleted, with knockout parasites displaying reduced grow-rates, both in vivo and
      in vitro, and reduced capacity to cause severe disease in a cerebral malaria
      model. Thus, while not essential for parasite survival, TRX2 may help to optimize
      PTEX activity. Importantly, the generation of TRX2 knockout parasites that
      display altered phenotypes provides a much-needed tool to dissect PTEX function. 

PMID- 23869530
TI  - Abortion-breast cancer study not valid for assessing overall association.

PMID- 23869531
TI  - Vogt-Koyanagi-Harada disease in an adolescent boy.
AB  - Vogt-Koyanagi-Harada (VKH) disease is a rare multiorgan disorder that affects the
      melanocytes of the eyes, skin, inner ear, and meninges. It is more common in
      women and in patients 30 to 50 years of age; it is rarely seen in children. We
      report a 14-year-old boy who meets the criteria for complete VKH disease. 

PMID- 23869532
TI  - Factors associated with utilisation of traditional Chinese medicine among Hong
      Kong Chinese.
AB  - The present study explored factors associated with belief in, and utilisation of,
      traditional Chinese medicine (TCM), as well as factors associated with trust in
      TCM practitioners (TCMPs) among Hong Kong Chinese individuals. Data were
      collected using a structured questionnaire. A sample of 300 Hong Kong Chinese
      aged between 18 and 90 years old were recruited. The study used a number of
      outcome variables including demographic variables, health status, as measured by
      the SF-12, attitude towards TCM and Western medicine as measured by the Chinese
      Western Medical Beliefs Scale, traditional Chinese values as measured by the
      Chinese Values Scale and trust in physicians. Findings revealed an association
      between age, gender and education level, with older age, being female and lower
      educational attainment all being predictive of TCM utilisation. Utilisation norms
      was predictive of trust in practitioners, indicating that frequent use of TCM
      lead to higher levels of trust in TCMP. Chinese values were differentially
      associated with use of and belief in TCM. Confucian obligation was predictive of
      belief in TCM and utilisation of TCM, while tolerance and harmony was not
      associated with belief and use of TCM. Younger respondents tended to score higher
      in tolerance and harmony, while older respondents scored higher in Confucian
      obligation, which goes some way to explain these differing trends in Chinese
      values and associations with TCM as older respondents were much more likely to
      utilise TCM than their younger counterparts. 

PMID- 23869533
TI  - Accounting for the biogeochemical cycle of nitrogen in input-output life cycle
      assessment.
AB  - Nitrogen is indispensable for sustaining human activities through its role in the
      production of food, animal feed, and synthetic chemicals. This has encouraged
      significant anthropogenic mobilization of reactive nitrogen and its emissions
      into the environment resulting in severe disruption of the nitrogen cycle. This
      paper incorporates the biogeochemical cycle of nitrogen into the 2002 input
      output model of the U.S. economy. Due to the complexity of this cycle, this work
      proposes a unique classification of nitrogen flows to facilitate understanding of
      the interaction between economic activities and various flows in the nitrogen
      cycle. The classification scheme distinguishes between the mobilization of inert
      nitrogen into its reactive form, use of nitrogen in various products, and
      nitrogen losses to the environment. The resulting inventory and model of the US
      economy can help quantify the direct and indirect impacts or dependence of
      economic sectors on the nitrogen cycle. This paper emphasizes the need for
      methods to manage the N cycle that focus not just on N losses, which has been the
      norm until now, but also include other N flows for a more comprehensive view and
      balanced decisions. Insight into the N profile of various sectors of the 2002
      U.S. economy is presented, and the inventory can also be used for LCA or Hybrid
      LCA of various products. The resulting model is incorporated in the approach of
      Ecologically-Based LCA and available online. 

PMID- 23869535
TI  - Microswitch-aided programs with contingent stimulation versus general stimulation
      programs for post-coma persons with multiple disabilities.
AB  - OBJECTIVE: Assessing the impact of microswitch-aided programs with contingent
      stimulation on response engagement (Study I) and post-session alertness (Study
      II) of post-coma participants with multiple disabilities. METHOD: Study I
      included three participants whose scores on the Coma Recovery Scale-Revised (CRS
      R) were 11 or 13. Study II included three participants whose CRS-R scores were
      19, 13, and 14. In both studies, the participants received sessions with
      contingent stimulation (i.e., sessions in which activation of a microswitch with
      an eyelid or hand response produced 15 s of preferred stimulation) and sessions
      with general, non-contingent stimulation (i.e., stimulation lasted throughout the
      sessions). RESULTS: Study I showed an increase in response engagement/frequencies
      only during the contingent stimulation sessions. Study II showed that the
      participants' level of vigilance after those sessions was higher than after non
      contingent stimulation sessions. CONCLUSION: Microswitch-aided programs with
      contingent stimulation would be more beneficial than programs with general/non
      contingent stimulation.

PMID- 23869534
TI  - Safety of spironolactone in dogs with chronic heart failure because of
      degenerative valvular disease: a population-based, longitudinal study.
AB  - BACKGROUND: Spironolactone treatment in humans is associated with an increased
      risk of hyperkalemia and renal dysfunction. HYPOTHESIS: Dogs with cardiac disease
      treated with spironolactone, in addition to conventional therapy, are not at
      higher risk for adverse events (AEs) than those receiving solely conventional
      therapy. ANIMALS: One hundred and ninety-six client-owned dogs with naturally
      occurring myxomatous mitral valve disease. METHODS: Prospective, double-blinded
      field study with dogs randomized to receive either spironolactone (2 mg/kg once a
      day) or placebo in addition to conventional therapy (angiotensin-converting
      enzyme inhibitor, plus furosemide and digoxin if needed). Safety was compared
      between treatment groups, using the frequency of AEs, death caused by cardiac
      disease, renal disease, or both, and variations in serum sodium, potassium, urea,
      and creatinine concentrations. For the latter, population-specific reference
      intervals were established and out of range values (ORV) analyzed. RESULTS: The
      number of AEs was similar in the spironolactone and reference groups (188 and
      208, respectively), when followed for median duration of 217 days (range [2
      1,333]). At each study time point, the percentage of dogs showing ORV was similar
      between groups. There were a higher number of deaths because of cardiac disease,
      renal disease or both in the reference group (30.7% versus 13.7%) (P = .0043).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with heart failure receiving
      spironolactone in addition to conventional treatment are not at a higher risk for
      AEs, death caused by cardiac disease, renal disease, or both, hyperkalemia, or
      azotemia.

PMID- 23869536
TI  - Two new antioxidant diarylheptanoids from the fruits of Alpinia oxyphylla.
AB  - Two new diarylheptanoids, 1-(3',5'-dihydroxy-4'-methoxyphenyl)-7-phenyl-3
      heptanone (1) and 1-(2',4'-dihydroxy-3'-methoxyphenyl)-7-(4"-methoxyphenyl)-3
      heptanone (2), along with known diarylheptanoid yakuchinone A (3), and five
      flavanoids, tectochrysin (4), chrysin (5), izalpinin (6), kaempferol 7, 4'
      dimethyl ether (7), and kaempferide (8) were isolated from the fruits of Alpinia
      oxyphylla Miq. Their structures were determined by means of spectroscopic
      methods. Antioxidant activities of all the isolated compounds were evaluated
      using a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Compounds 1-3 and 6-8
      exhibited potent antioxidant activities in the DPPH assay. 

PMID- 23869538
TI  - Thinking inside the box: the health cube paradigm for health and wellness program
      evaluation and design.
AB  - Appropriately constructed health promotions can improve population health. The
      authors developed a practical model for designing, evaluating, and improving
      initiatives to provide optimal value. Three independent model dimensions (impact,
      engagement, and sustainability) and the resultant three-dimensional paradigm were
      described using hypothetical case studies, including a walking challenge, a
      health risk assessment survey, and an individual condition management program.
      The 3-dimensional model is illustrated and the dimensions are defined.
      Calculation of a 3-dimensional score for program comparisons, refinements, and
      measurement is explained. Program 1, the walking challenge, had high engagement
      and impact, but limited sustainability. Program 2, the health risk assessment
      survey, had high engagement and sustainability but limited impact. Program 3, the
      on-site condition management program, had measurable impact and sustainability
      but limited engagement, because of a lack of program capacity. Each initiative,
      though successful in 2 dimensions, lacked sufficient evolution along the third
      axis for optimal value. Calculation of a 3-dimensional score is useful for health
      promotion program development comparison and refinements, and overall measurement
      of program success.

PMID- 23869539
TI  - Impact of compliance to oral hypoglycemic agents on short-term disability costs
      in an employer population.
AB  - This study evaluated the relationships between compliance with oral hypoglycemic
      agents and health care/short-term disability costs in a large manufacturing
      company. The retrospective analysis used an observational cohort drawn from
      active employees of Ford Motor Company. The study population consisted of 4978
      individuals who were continuously eligible for 3 years (between 2001-2007) and
      who received a prescription for an oral hypoglycemic agent during that time.
      Medical, pharmacy, and short-term disability claims data were obtained from the
      University of Michigan Health Management Research Center data warehouse. Pharmacy
      claims/refill data were used to calculate the proportion of days covered (PDC);
      an individual was classified as compliant if his/her PDC was >=80%. Model
      covariates included age, sex, work type, and Charlson comorbidity scores. The
      impact of compliance on disability and health care costs was measured by
      comparing the costs of the compliant with those of the noncompliant during a 1
      year follow-up. Among these employees, compliant patients had lower medical,
      higher pharmacy, and lower short-term disability costs than did the noncompliant.
      After adjusting for demographics and comorbidity, noncompliance was associated
      with statistically higher short-term disability costs ($1840 vs. $1161,
      P<0.0001), longer short-term disability duration, and an increase in short-term
      disability incidence (21.5% of the noncompliant had a claim compared to 16.0% of
      the compliant, P<0.0001). These results suggest that medication compliance may be
      important in curtailing the rise of health care/disability costs in the
      workplace. Employers concerned with the total costs associated with diabetes
      should not overlook the impact of compliance on short-term disability.

PMID- 23869540
TI  - Value drivers: an approach for estimating health and disease management program
      savings.
AB  - Health and disease management (HDM) programs have faced challenges in documenting
      savings related to their implementation. The objective of this eliminate study
      was to describe OptumHealth's (Optum) methods for estimating anticipated savings
      from HDM programs using Value Drivers. Optum's general methodology was reviewed,
      along with details of 5 high-use Value Drivers. The results showed that the Value
      Driver approach offers an innovative method for estimating savings associated
      with HDM programs. The authors demonstrated how real-time savings can be
      estimated for 5 Value Drivers commonly used in HDM programs: (1) use of beta
      blockers in treatment of heart disease, (2) discharge planning for high-risk
      patients, (3) decision support related to chronic low back pain, (4) obesity
      management, and (5) securing transportation for primary care. The validity of
      savings estimates is dependent on the type of evidence used to gauge the
      intervention effect, generating changes in utilization and, ultimately, costs.
      The savings estimates derived from the Value Driver method are generally
      reasonable to conservative and provide a valuable framework for estimating
      financial impacts from evidence-based interventions.

PMID- 23869537
TI  - TGF-beta2, a protective intestinal cytokine, is abundant in maternal human milk
      and human-derived fortifiers but not in donor human milk.
AB  - OBJECTIVE: This study compared cytokines (in particular transforming growth
      factor [TGF]-beta2) and lactoferrin in maternal human milk (MHM), human-derived
      milk fortifier (HDMF), and donor human milk (DHM). MATERIALS AND METHODS: MHM was
      randomly collected from breastfeeding mothers who had no infectious illness at
      the time of milk expression. HDMF and DHM were products derived from human milk
      processed by Holder pasteurization. MHM samples were collected at different times
      (early/late) and gestations (preterm/term). Lactoferrin was analyzed by western
      blotting, and cytokines were quantified using commercial enzyme-linked
      immunosorbent assays. Significance was determined using analysis of variance.
      RESULTS: In the 164 samples analyzed, TGF-beta2 concentrations in HDMF and
      preterm MHM (at all collection times) were fivefold higher than in DHM (p<0.05).
      Early preterm MHM had levels of interleukin (IL)-10 and IL-18, 11-fold higher
      than DHM (p<0.05). IL-6 in DHM was 0.3% of the content found in MHM. IL-18 was
      fourfold higher in early MHM versus late MHM regardless of gestational age
      (p<0.05). Lactoferrin concentration in DHM was 6% of that found in MHM.
      CONCLUSIONS: Pasteurization decreases concentrations of most cytokines and
      lactoferrin in DHM. TGF-beta2, a protective intestinal cytokine, has comparable
      concentrations in HDMF to MHM despite pasteurization.

PMID- 23869541
TI  - An interspecific comparison between morphology and swimming performance in
      cyprinids.
AB  - Flow regimes are believed to be of major evolutionary significance in fish. The
      flow regimes inhabited by cyprinids vary extensively from still flow regimes to
      riptide flow regimes. To test (i) whether flow-driven swimming performance and
      relevant morphological differentiation are present among fish species and (ii)
      whether evolutionary shifts between high-flow and low-flow habitats in cyprinids
      are associated with evolutionary trade-offs in locomotor performance, we obtained
      data on both steady and unsteady swimming performance and external body shape for
      19 species of cyprinids that typically occur in different flow regimes (still,
      intermediate and riptide). We also measured the routine energy expenditure (RMR)
      and maximum metabolic rate (MMR) and calculated the optimal swimming speed. Our
      results showed that fish species from riptide groups tend to have a higher
      critical swimming speed (Ucrit ), maximum linear velocity (Vmax ) and fineness
      ratio (FR) than fish from the other two groups. However, there was no correlation
      between the reconstructed changes in the steady and unsteady swimming performance
      of the 19 species. According to the phylogenetically independent contrast (PIC)
      method, the Ucrit was actively correlated with the MMR. These results indicated
      that selection will favour both higher steady and unsteady swimming performance
      and a more streamlined body shape in environments with high water velocities. The
      results suggested that steady swimming performance was more sensitive to the flow
      regime and that for this reason, changes in body shape resulted more from
      selective pressure on steady swimming performance than on unsteady swimming
      performance. No evolutionary trade-off was observed between steady and unsteady
      swimming performance, although Ucrit and MMR were found to have coevolved.
      However, a further analysis within each typically occurring habitat group
      suggested that the trade-off that may exist between steady and unsteady swimming
      performance may be concealed by the effect of habitat. 

PMID- 23869543
TI  - Balancing potential risks and benefits of hemoglobin-based oxygen carriers.
AB  - Hemoglobin-based oxygen carriers (HBOCs) are thought to have an adverse
      risk:benefit profile when compared to that of transfusing stored red blood cells
      (RBCs). However, there are clinical circumstances when RBC transfusion is not an
      option (e.g., patient refusal, unavailability owing to issues of compatibility or
      remote location). For these circumstances assessment of the risks of an HBOC
      should be compared to the risks of untransfused acute anemia. In this article we
      compare the risk of allowing a patient with severe anemia to have a further small
      decrease in hemoglobin (Hb) concentration to the risk of infusing an HBOC. We
      conclude that at Hb concentrations less than 6 g/dL, the risk of a further
      decrease in Hb concentration greatly exceeds the risk of HBOC infusion. Thus, we
      suggest that there may be a place for use of HBOCs when RBC transfusion is not an
      option.

PMID- 23869542
TI  - Factors associated with delayed gastric emptying after pancreaticoduodenectomy.
AB  - BACKGROUND: The factors associated with delayed gastric emptying (DGE) after a
      pancreaticoduodenectomy (PD) are not definitively known. METHODS: From November
      2011 through to May 2012, data were prospectively collected on 711 patients
      undergoing a pancreaticoduodenectomy or total pancreatectomy as part of the
      American College of Surgeons-National Surgical Quality Improvement Program
      Pancreatectomy Demonstration Project. Bivariate and multivariate models were
      employed to determine the factors that predicted DGE. RESULTS: In the 711
      patients, the overall rate of DGE was 20.1%. In a bivariate analysis, intra
      operative factors such as pylorus-preservation (47.1% versus 43.7%, P = 0.40),
      intra-operative drain placement (85.5%, versus 85.1%, P = 0.91) and an antecolic
      compared with a retrocolic gastrojejunostomy (60.1% versus 65.1%, P = 0.26) were
      not different between the DGE and no DGE groups. Pancreatic fistula formation
      (31.2% versus 10.1%), post-operative sepsis (21.7% versus 7.0%), organ space
      surgical site infection (SSI) (23.9% versus 7.9%), need for percutaneous drainage
      (23.0% versus 10.6%) and reoperation (10.6% versus 3.1%) were higher in patients
      with DGE (P < 0.0001). In a multivariable model, only pancreatic fistula, post
      operative sepsis and reoperation were independently associated with DGE.
      DISCUSSION: In this multicentre study, only post-operative complications were
      associated with DGE. Neither pylorus preservation nor route of enteric
      reconstruction (antecolic versus retrocolic) was associated with delayed gastric
      emptying.

PMID- 23869544
TI  - Water-soluble naphthalene diimides as singlet oxygen sensitizers.
AB  - Bromo- and/or alkylamino-substituted and hydrosoluble naphthalene diimides (NDIs)
      were synthesized to study their multimodal photophysical and photochemical
      properties. Bromine-containing NDIs (i.e., 11) behaved as both singlet oxygen
      ((1)O2) photosensitizers and fluorescent molecules upon irradiation at 532 nm.
      Among the NDIs not containing Br, only 12 exhibited photophysical properties
      similar to those of Br-NDIs, by irradiation above 610 nm, suggesting that for
      these NDIs both singlet and triplet excited-state properties are strongly
      affected by length, structure of the solubilizing moieties, and pH of the
      solution. Laser flash photolysis confirmed that the NDI lowest triplet excited
      state was efficiently populated, upon excitation at both 355 and 532 nm, and that
      free amine moieties quenched both the singlet and triplet excited states by
      intramolecular electron transfer, with generation of detectable radical anions.
      Time-resolved experiments, monitoring the 1270 nm (1)O2 phosphorescence decay
      generated upon laser irradiation at 532 nm, allowed a ranking of the NDIs as
      sensitizers, based on their (1)O2 quantum yields (PhiDelta). The
      tetrafunctionalized 12, exhibiting a long-lived triplet state (tau ~ 32 MUs) and
      the most promising absorptivity for photodynamic therapy application, was tested
      as efficient photosensitizers in the photo-oxidations of 1,5-dihydroxynaphthalene
      and 9,10-anthracenedipropionic acid in acetonitrile and water.

PMID- 23869545
TI  - Probing the bonding in nitrogen-doped graphene using electron energy loss
      spectroscopy.
AB  - Precise control of graphene properties is an essential step toward the
      realization of future graphene devices. Defects, such as individual nitrogen
      atoms, can strongly influence the electronic structure of graphene. Therefore,
      state-of-the-art characterization techniques, in conjunction with modern modeling
      tools, are necessary to identify these defects and fully understand the
      synthesized material. We have directly visualized individual substitutional
      nitrogen dopant atoms in graphene using scanning transmission electron microscopy
      and conducted complementary electron energy loss spectroscopy experiments and
      modeling which demonstrates the influence of the nitrogen atom on the carbon K
      edge. 

PMID- 23869546
TI  - Synthesis of clionamine B, an autophagy stimulating aminosteroid isolated from
      the sponge Cliona celata.
AB  - Clionamine B (2), an aminosteroid isolated from the marine sponge Cliona celata,
      has been synthesized starting from the plant sapogenin tigogenin (5). A key step
      in the synsthesis is the stereoselective introduction of the C-20 alpha-hydroxyl
      substituent via oxidation of a gamma-lactone enolate with molecular oxygen.
      Synthetic clionamine B (2) strongly stimulated autophagy in human breast cancer
      MCF-7 cells. 

PMID- 23869547
TI  - Impact of a decision rule on duration of continuous cardiac monitoring of
      patients with suspected acute coronary syndrome in an emergency department.
AB  - BACKGROUND/AIMS: To determine the effect of introducing a decision rule on the
      duration of continuous cardiac monitoring (CCM) for patients with suspected acute
      coronary syndrome in an adult emergency department (ED). METHODS: This was a
      retrospective observational study of 220 patients with suspected acute coronary
      syndrome made up of two consecutive cohorts collected before and after
      introduction in July 2010 of a decision rule that made use of a new high
      sensitivity troponin T assay. The primary outcome was median CCM duration in the
      ED (CCMED). Secondary outcomes were median duration of CCM in the first 24 h,
      rate of adverse events, proportion of patients after the intervention who had the
      rule adhered to, and estimated median CCMED had the decision rule been adhered to
      by all patients. RESULTS: The decision rule was adhered to in 59.3% (95%
      confidence interval 49.8-68.1) of patients post-intervention. There was no
      statistically or clinically significant difference in median CCMED before (240
      min, interquartile range 156-313) and after (230 min interquartile range 145-353)
      introduction of the decision rule (P = 0.74) nor in CCM in the first 24 h (908
      min vs 929 min). Seven (3.2%, 95% confidence interval 1.4-6.6) adverse events
      occurred overall. All three patients with adverse events after the intervention
      were monitored in ED according to the decision rule. CONCLUSION: Introduction of
      this decision rule did not decrease the median CCMED. All adverse events after
      the intervention occurred in appropriately monitored patients, including patients
      with initially negative high-sensitivity troponin T, suggesting that the decision
      rule would not compromise patient safety.

PMID- 23869548
TI  - Structure prediction of GPCRs using piecewise homologs and application to the
      human CCR5 chemokine receptor: validation through agonist and antagonist docking.
AB  - This article describes the construction and validation of a three-dimensional
      model of the human CC chemokine receptor 5 (CCR5) receptor using multiple
      homology modeling. A new methodology is presented where we built each secondary
      structural model of the protein separately from distantly related homologs of
      known structure. The reliability of our approach for G-protein coupled receptors
      was assessed through the building of the human C-X-C chemokine receptor type 4
      (CXCR4) receptor of known crystal structure. The models are refined using
      molecular dynamics simulations and energy minimizations using CHARMM, a classical
      force field for proteins. Finally, docking models of both the natural agonists
      and the antagonists of the receptors CCR5 and CXCR4 are proposed. This study
      explores the possible binding process of ligands to the receptor cavity of
      chemokine receptors at molecular and atomic levels. We proposed few crucial
      residues in receptors binding to agonist/antagonist for further validation
      through experimental analysis. In particular, our study provides better
      understanding of the blockage mechanism of the chemokine receptors CCR5 and
      CXCR4, and may help the identification of new lead compounds for drug development
      in HIV infection, inflammatory diseases, and cancer metastasis. 

PMID- 23869549
TI  - Neonatal immunization with respiratory syncytial virus glycoprotein fragment
      induces protective immunity in the presence of maternal antibodies in mice.
AB  - Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory
      tract infections in infants and the elderly worldwide. The significant morbidity
      and mortality associated with this infection underscores the urgent need for
      development of RSV vaccine. In this study, we first show that intranasal
      administration of RSV glycoprotein core fragment (Gcf) to neonatal mice can
      induce systemic humoral immune responses and protective immunity against RSV
      without causing lung eosinophilia, although antibody response was shifted to a
      Th2 response. Next, we examined whether the presence of maternal anti-RSV
      antibodies would affect the responsiveness and protection efficacy of Gcf in
      newborn mice, since infants can possess RSV-specific maternal antibodies due to
      frequent RSV re-infections to adults. Intranasal administration of Gcf induced
      antibody response and increased IFNgamma secretion and protected mice against RSV
      challenge without severe lung eosinophilia, even in the presence of high levels
      of RSV-specific maternal antibodies. Thus, our findings suggest that Gcf may be
      an effective and safe RSV vaccine during the neonatal period.

PMID- 23869550
TI  - Biallelic losses of 13q do not confer a poorer outcome in chronic lymphocytic
      leukaemia: analysis of 627 patients with isolated 13q deletion.
AB  - Losses in 13q as a sole abnormality confer a good prognosis in chronic
      lymphocytic leukaemia (CLL). Nevertheless, its heterogeneity has been
      demonstrated and the clinical significance of biallelic 13q deletions remains
      controversial. We compared the clinico-biological characteristics of a series of
      627 patients harbouring isolated 13q deletions by fluorescence in situ
      hybridization (FISH), either monoallelic (13q * 1), biallelic (13q * 2), or the
      coexistence of both clones (13qM). The most frequent 13q deletion was 13q * 1
      (82.1%), while 13q * 2 and 13qM represented 8.6% and 9.3% of patients
      respectively. The median percentage of altered nuclei significantly differed
      across groups: 55%, 72.5% and 80% in 13q * 1, 13q * 2 and 13qM (P < 0.001).
      However, no significant differences in the clinical outcome among 13q groups were
      found. From 84 patients with sequential FISH studies, eight patients lost the
      remaining allele of 13q whereas none of them changed from 13q * 2 to the 13q * 1
      group. The percentage of abnormal cells detected by FISH had a significant impact
      on the five-year cumulative incidence of treatment and the overall survival, 90%
      being the highest predictive power cut-off. In conclusion, loss of the remaining
      13q allele is not enough to entail a worse prognosis in CLL. The presence of
      isolated 13q deletion can be risk-stratified according to the percentage of
      altered cells.

PMID- 23869551
TI  - Estimating resource acquisition and at-sea body condition of a marine predator.
AB  - 1. Body condition plays a fundamental role in many ecological and evolutionary
      processes at a variety of scales and across a broad range of animal taxa. An
      understanding of how body condition changes at fine spatial and temporal scales
      as a result of interaction with the environment provides necessary information
      about how animals acquire resources. 2. However, comparatively little is known
      about intra- and interindividual variation of condition in marine systems. Where
      condition has been studied, changes typically are recorded at relatively coarse
      time-scales. By quantifying how fine-scale interaction with the environment
      influences condition, we can broaden our understanding of how animals acquire
      resources and allocate them to body stores. 3. Here we used a hierarchical
      Bayesian state-space model to estimate the body condition as measured by the size
      of an animal's lipid store in two closely related species of marine predator that
      occupy different hemispheres: northern elephant seals (Mirounga angustirostris)
      and southern elephant seals (Mirounga leonina). The observation model linked
      drift dives to lipid stores. The process model quantified daily changes in lipid
      stores as a function of the physiological condition of the seal (lipid:lean
      tissue ratio, departure lipid and departure mass), its foraging location, two
      measures of behaviour and environmental covariates. 4. We found that
      physiological condition significantly impacted lipid gain at two time-scales -
      daily and at departure from the colony - that foraging location was significantly
      associated with lipid gain in both species of elephant seals and that long-term
      behavioural phase was associated with positive lipid gain in northern and
      southern elephant seals. In northern elephant seals, the occurrence of short-term
      behavioural states assumed to represent foraging were correlated with lipid gain.
      Lipid gain was a function of covariates in both species. Southern elephant seals
      performed fewer drift dives than northern elephant seals and gained lipids at a
      lower rate. 5. We have demonstrated a new way to obtain time series of body
      condition estimates for a marine predator at fine spatial and temporal scales.
      This modelling approach accounts for uncertainty at many levels and has the
      potential to integrate physiological and movement ecology of top predators. The
      observation model we used was specific to elephant seals, but the process model
      can readily be applied to other species, providing an opportunity to understand
      how animals respond to their environment at a fine spatial scale.

PMID- 23869552
TI  - Differentiated roles for MreB-actin isologues and autolytic enzymes in Bacillus
      subtilis morphogenesis.
AB  - Cell morphogenesis in most bacteria is governed by spatiotemporal growth
      regulation of the peptidoglycan cell wall layer. Much is known about
      peptidoglycan synthesis but regulation of its turnover by hydrolytic enzymes is
      much less well understood. Bacillus subtilis has a multitude of such enzymes. Two
      of the best characterized are CwlO and LytE: cells lacking both enzymes have a
      lethal block in cell elongation. Here we show that activity of CwlO is regulated
      by an ABC transporter, FtsEX, which is required for cell elongation, unlike cell
      division as in Escherichia coli. Actin-like MreB proteins are thought to play a
      key role in orchestrating cell wall morphogenesis. B. subtilis has three MreB
      isologues with partially differentiated functions. We now show that the three
      MreB isologues have differential roles in regulation of the CwlO and LytE systems
      and that autolysins control different aspects of cell morphogenesis. The results
      add major autolytic activities to the growing list of functions controlled by
      MreB isologues in bacteria and provide new insights into the different
      specialized functions of essential cell wall autolysins. 

PMID- 23869553
TI  - Acyclic germylones: congeners of allenes with a central germanium atom.
AB  - The cyclic alkyl(amino) carbene (cAAC:)-stabilized acyclic germylones (Me2
      cAAC:)2Ge (1) and (Cy2-cAAC:)2Ge (2) were prepared utilizing a one-pot synthesis
      of GeCl2(dioxane), cAAC:, and KC8 in a 1:2:2.1 molar ratio. Dark green crystals
      of compounds 1 and 2 were produced in 75 and 70% yields, respectively. The
      reported methods for the preparation of the corresponding silicon compounds
      turned out to be not applicable in the case of germanium. The single-crystal X
      ray structures of 1 and 2 feature the C-Ge-C bent backbone, which possesses a
      three-center two-electron pi-bond system. Compounds 1 and 2 are the first acyclic
      germylones containing each one germanium atom and two cAAC: molecules. EPR
      measurements on compounds 1 and 2 confirmed the singlet spin ground state. DFT
      calculations on 1/2 revealed that the singlet ground state is more stable by ~16
      to 18 kcal mol(-1) than that of the triplet state. First and second proton
      affinity values were theoretically calculated to be of 265.8 (1)/267.1 (2) and
      180.4 (1)/183.8 (2) kcal mol(-1), respectively. Further calculations, which were
      performed at different levels suggest a singlet diradicaloid character of 1 and
      2. The TD-DFT calculations exhibit an absorption band at ~655 nm in n-hexane
      solution that originates from the diradicaloid character of germylones 1 and 2.

PMID- 23869554
TI  - Evaluating the efficacy of treatments for haemorrhoids: time for a standardized
      definition of recurrence?

PMID- 23869555
TI  - Quantitative proteomics reveals diverse roles of miR-148a from gastric cancer
      progression to neurological development.
AB  - MicroRNAs (miRNAs) are noncoding RNAs that control gene expression either by
      degradation of mRNAs or inhibition of protein translation. miR-148a has been
      reported to have the impacts on tumor progression. Here, a quantitative
      proteomics combined with stable isotope labeling was applied to identify the
      global profile of miR-148a-regulated downstream proteins. The data have been
      deposited to the ProteomeXchange with identifier PXD000190. A total of 2938
      proteins were quantified, and 55 proteins were considered to be regulated by miR
      148a. We found that not only proteins associated with cancer progression but also
      molecules involved in neural development were regulated by miR-148a. This study
      is the first to identify the function of miR-148a in neural development by using
      a proteomic approach. Analysis of a public clinical database also showed that the
      patients with neural diseases could display abnormal expression of miR-148a.
      Moreover, silencing of miR-148a led to the abnormal morphology and decreased
      expression of neuron-related markers in the developing brain of zebrafish. These
      results provided important insight into the regulation of neurological
      development elicited by miR-148a. 

PMID- 23869556
TI  - Single-pair fluorescence resonance energy transfer analysis of mRNA transcripts
      for highly sensitive gene expression profiling in near real time.
AB  - Expression analysis of mRNAs transcribed from certain genes can be used as
      important sources of biomarkers for in vitro diagnostics. While the use of
      reverse transcription quantitative PCR (RT-qPCR) can provide excellent analytical
      sensitivity for monitoring transcript numbers, more sensitive approaches for
      expression analysis that can report results in near real-time are needed for many
      critical applications. We report a novel assay that can provide exquisite limits
      of-quantitation and consists of reverse transcription (RT) followed by a ligase
      detection reaction (LDR) with single-pair fluorescence resonance energy transfer
      (spFRET) to provide digital readout through molecular counting. For this assay,
      no PCR was employed, which enabled short assay turnaround times. To facilitate
      implementation of the assay, a cyclic olefin copolymer (COC) microchip, which was
      fabricated using hot embossing, was employed to carry out the LDR in a continuous
      flow format with online single-molecule detection following the LDR. As
      demonstrators of the assay's utility, MMP-7 mRNA was expression profiled from
      several colorectal cancer cell lines. It was found that the RT-LDR/spFRET assay
      produced highly linear calibration plots even in the low copy number regime.
      Comparison to RT-qPCR indicated a better linearity over the low copy number range
      investigated (10-10,000 copies) with an R(2) = 0.9995 for RT-LDR/spFRET and R(2)
      = 0.98 for RT-qPCR. In addition, differentiating between copy numbers of 10 and
      50 could be performed with higher confidence using RT-LDR/spFRET. To demonstrate
      the short assay turnaround times obtainable using the RT-LDR/spFRET assay, a two
      thermal cycle LDR was carried out on amphiphysin gene transcripts that can serve
      as important diagnostic markers for ischemic stroke. The ability to supply
      diagnostic information on possible stroke events in short turnaround times using
      RT-LDR/spFRET will enable clinicians to treat patients effectively with
      appropriate time-sensitive therapeutics.

PMID- 23869557
TI  - Use of multicriteria decision analysis to address conservation conflicts.
AB  - Conservation conflicts are increasing on a global scale and instruments for
      reconciling competing interests are urgently needed. Multicriteria decision
      analysis (MCDA) is a structured, decision-support process that can facilitate
      dialogue between groups with differing interests and incorporate human and
      environmental dimensions of conflict. MCDA is a structured and transparent method
      of breaking down complex problems and incorporating multiple objectives. The
      value of this process for addressing major challenges in conservation conflict
      management is that MCDA helps in setting realistic goals; entails a transparent
      decision-making process; and addresses mistrust, differing world views, cross
      scale issues, patchy or contested information, and inflexible legislative tools.
      Overall we believe MCDA provides a valuable decision-support tool, particularly
      for increasing awareness of the effects of particular values and choices for
      working toward negotiated compromise, although an awareness of the effect of
      methodological choices and the limitations of the method is vital before applying
      it in conflict situations.

PMID- 23869558
TI  - Patient characteristics of neonatal eosinophilic pustulosis.
AB  - A 10-week old preterm infant boy presented with a pustular eruption of the face
      and blood eosinophilia. Histology demonstrated eosinophils without predominant
      follicular involvement. The lesions healed without intervention within 2 months.
      The presentation was consistent with neonatal eosinophilic pustulosis. We discuss
      the similarities between cases described in the literature and suggest that this
      entity affects a unique patient population of preterm infants. 

PMID- 23869559
TI  - Novel coronary artery anomaly in an English Bulldog with pulmonic stenosis.

PMID- 23869560
TI  - Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA-independent
      virulence.
AB  - The type-VII ESX-1 secretion apparatus, encoded by the esx-1 genetic locus, is
      essential for the export of EsxA and EsxB, two major virulence factors of
      Mycobacterium tuberculosis. ESX-1 also requires the products of the unlinked
      espACD operon for optimal function and these proteins are considered integral
      parts of the secretion apparatus. Here we show that the espACD operon is not
      necessary for the secretion of EspB, another ESX-1 substrate, and this unimpeded
      secretion of EspB is associated with significant residual virulence. Upon further
      investigation, we found that purified EspB can facilitate M. tb virulence even in
      the absence of EsxA and EsxB, and may do so by binding the bioactive
      phospholipids phosphatidic acid and phosphatidylserine, both of which are potent
      bioactive molecules with prominent roles in eukaryotic cell signalling. Our
      findings provide new insights into the impact of the espACD operon on the ESX-1
      apparatus and reveal a distinct virulence function for EspB with novel
      implications in M. tb-host interactions. 

PMID- 23869561
TI  - Respiratory muscle force and lung volume changes in a population of children with
      sickle cell disease.
AB  - Sickle cell disease (SCD) is a disorder known to impact the respiratory system.
      We sought to identify respiratory muscle force and lung volume relationships in a
      paediatric SCD population. Thirty-four SCD-SS subjects underwent pulmonary
      function testing. Height, weight, age, and gender-adjusted percent predicted
      maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) values
      were compared to spirometry and lung volumes. Statistical analyses were performed
      using Pearson's correlation coefficient and paired two-tailed t-test. The mean +/
      standard deviation (SD) MIP and MEP was 69.6 +/- 31.6 cm H2 O and 66.9 +/- 22.9
      cm H2 O, respectively, and mean +/- SD percent predicted MIP (101.3 +/- 45.9)
      exceeded MEP (72.1 +/- 26.0) (P = 0.002). MIP correlated with forced vital
      capacity (FVC; r = 0.51, P = 0.001) and TLC (r = 0.54, P < 0.0001). MEP also
      correlated with FVC (r = 0.43, P = 0.011) and total lung capacity (TLC; r = 0.42,
      P = 0.013). Pearson's correlation coefficient testing yielded relationships
      between MIP and MEP (r = 0.64, P < 0.0001). SCD-SS patients showed correlations
      between respiratory muscle force and lung volume, and reduced percent predicted
      expiratory muscle force compared to inspiratory muscle force. Respiratory muscle
      strength may affect lung volumes in these patients, and expiratory muscles may be
      more susceptible than the diaphragm to SCD-induced vaso-occlusive damage.

PMID- 23869562
TI  - The plant-specific transcription factor gene NAC103 is induced by bZIP60 through
      a new cis-regulatory element to modulate the unfolded protein response in
      Arabidopsis.
AB  - The unfolded protein response (UPR) plays important roles in plant development
      and plant-pathogen interactions, as well as in plant adaptation to adverse
      environmental stresses. Previously bZIP28 and bZIP60 have been identified as
      important UPR regulators for mitigating the endoplasmic reticulum (ER) stress in
      Arabidopsis thaliana. Here we report the biological function of NAC103 in a novel
      transcriptional regulatory cascade, connecting bZIP60 to the UPR downstream genes
      in Arabidopsis. Expression of NAC103 was induced by ER stress, and was completely
      abolished in the bZIP60 null mutant. A new ER stress-responsive cis-element UPRE
      III (TCATCG) on the NAC103 promoter was identified, and trans-activation of UPRE
      III by bZIP60 was confirmed in both yeast cells and Arabidopsis protoplasts. The
      direct binding of bZIP60 to UPRE-III-containing DNA was also demonstrated in an
      electrophoretic mobility shift assay. NAC103 formed homodimers in yeast two
      hybrid and bimolecular fluorescence complementation assays. It had
      transcriptional activation activity and was localized in the nucleus. Over
      expression of NAC103 had pleiotropic effects on plant growth, and induced
      expression of several UPR downstream genes in Arabidopsis under normal growth
      conditions. The activation of UPR gene promoters by NAC103 was also confirmed in
      effector/reporter protoplast assays. Thus, our study demonstrates a
      transcriptional regulatory cascade in which NAC103 relays ER stress signals from
      bZIP60 to UPR downstream genes through a newly identified ER stress cis-element
      (UPRE-III) and transcriptional activation activity of its encoded protein NAC103.

PMID- 23869563
TI  - Implementation of risk stratified antibiotic therapy for neutropenic fever: what
      are the risks?
AB  - BACKGROUND: A new national guideline for the management of febrile patients with
      severe neutropenia uses a risk stratification score to tailor treatment. AIMS: To
      evaluate the implementation of this guideline in a metropolitan teaching
      hospital. METHODS: A protocol was developed for implementation of the national
      guidelines for patients with neutropenic fever or at risk because of recent
      chemotherapy. Medical records of all patients presenting with fever to the
      haematology and oncology service for 3 months in 2011 were audited. Patients with
      a neutrophil count between 0.5 and 1.0 * 10(9) /L were classified as borderline
      neutropenia. RESULTS: Eighty-one episodes of fever were treated on the protocol.
      Forty-three per cent of patients were neutropenic. Uptake of the policy was low
      (35%) despite concerted efforts. The sensitivity and specificity of the
      Multinational Association for Supportive Care in Cancer score was 86% and 24%
      respectively. The readmission rate with fever was 19.2%. Median time to
      antibiotics was 60 min. Outcomes were similar for the neutropenic fever and
      borderline groups. Increasing treatment complexity was the major barrier to
      implementation. CONCLUSIONS: The majority of presentations with cancer and fever
      following chemotherapy do not have neutropenia but have similar outcomes when
      treated on the same pathway. The utility of the Multinational Association for
      Supportive Care in Cancer score was limited by uptake and specificity. Reducing
      time to antibiotics administration and readmission rates were identified as
      priorities. Implementation was labour-intensive and faced significant barriers.
      Prioritisation of evidence for translation requires attention to local priorities
      and implementation complexity. These results argue for a single sepsis guideline
      with treatment of cancer as a high-risk group.

PMID- 23869565
TI  - Are you doing what you want to do? Leisure preferences of adolescents with
      cerebral palsy.
AB  - OBJECTIVE: This study aimed at describing leisure activity preferences of
      adolescents with cerebral palsy (CP) and their relationship to participation and
      to identify factors associated with greater interest in particular leisure
      activities. METHODS: A cross-sectional design was used. Participants were
      adolescents (n = 127; 59.5% male; ages 12-19 years old; mean = 15.3; SD = 2.01
      years) with CP (GMFCS levels: I 40%, II 33%, III-IV 26%), who could complete the
      Preferences for Activities of Children (PAC) and other self-report
      questionnaires. RESULTS: Social (2.53; 0.38) and active-physical activities were
      most preferred (2.10; 0.42), and self-improvement activities were least preferred
      (1.93; 0.49). Preference for certain activities was not strongly associated with
      actual involvement in these activities. Family activity-orientation, family
      expressiveness, and adolescent's motivation explained 15% of the variance in
      preferences for social activities, and 37% of the variance in preferences for
      self-improvement activities. CONCLUSION: Family factors, personal factors, and
      functional abilities influence leisure preferences. Rehabilitation interventions
      should consider adolescents' preferences and family dynamics to promote leisure
      participation.

PMID- 23869566
TI  - Depression in older adults: a meta-synthesis.
AB  - Depression in older adults is often overlooked and dismissed as a part of aging.
      A body of knowledge-both quantitative and qualitative-has developed on the topic
      of depression in older adults. Meta-analyses and systematic reviews have been
      used to synthesize the quantitative findings of studies, and our research seeks
      to synthesize the qualitative studies that have been conducted on elders'
      experience with depression. Thirteen studies met inclusion criteria, and 4 major
      themes were extracted: experiences, causes, recovery, and barriers to treatment.
      These themes are detailed and their implications for practice are explored. 

PMID- 23869564
TI  - Biological and structural evaluation of 10R- and 10S-methylthio-DDACTHF reveals a
      new role for sulfur in inhibition of glycinamide ribonucleotide transformylase.
AB  - Glycinamide ribonucleotide transformylase (GAR Tfase) is a folate-dependent
      enzyme in the de novo purine biosynthesis pathway, which has long been considered
      a potential target for development of anti-neoplastic therapeutics. Here we
      report the biological and X-ray crystallographic evaluations of both independent
      C10 diastereomers, 10S- and 10R-methylthio-DDACTHF, bound to human GAR Tfase,
      including the highest-resolution apo GAR Tfase structure to date (1.52 A). Both
      diastereomers are potent inhibitors (Ki = 210 nM for 10R, and Ki = 180 nM for
      10S) of GAR Tfase and exhibit effective inhibition of human leukemia cell growth
      (IC50 = 80 and 50 nM, respectively). Their inhibitory activity was surprisingly
      high, and these lipophilic C10-substituted analogues show distinct advantages
      over their hydrophilic counterparts, most strikingly in retaining potency in
      mutant human leukemia cell lines that lack reduced folate carrier protein
      activity (IC50 = 70 and 60 nM, respectively). Structural characterization reveals
      a new binding mode for these diastereoisomers, in which the lipophilic thiomethyl
      groups penetrate deeper into a hydrophobic pocket within the folate-binding site.
      In silico docking simulations of three other sulfur-containing folate analogues
      also indicate that this hydrophobic cleft represents a favorable region for
      binding lipophilic substituents. Overall, these results suggest sulfur and its
      substitutions play an important role in not only the binding of anti-folates to
      GAR Tfase but also the selectivity and cellular activity (growth inhibition),
      thereby presenting new possibilities for the future design of potent and
      selective anti-folate drugs that target GAR Tfase.

PMID- 23869568
TI  - The direct effects of male killer infection on fitness of ladybird hosts
      (Coleoptera: Coccinellidae).
AB  - Male killing bacteria are common in insects and are thought to persist in host
      populations primarily by indirect fitness benefits to infected females, whereas
      direct fitness effects are generally assumed to be neutral or deleterious. Here,
      we estimated the effect of male killer infection on direct fitness (number of
      eggs laid, as a measure of fecundity, together with survival) and other life
      history traits (development time and body size) in seven ladybird host/male
      killer combinations. Effects of male killers on fecundity ranged, as expected,
      from costly to neutral; however, we found evidence of reduced development time
      and increased survival and body size in infected strains. Greater body size in
      Spiroplasma-infected Harmonia axyridis corresponded to greater ovariole number
      and therefore higher potential fecundity. To our knowledge, this is the first
      report of direct benefits of male killer infection after explicitly controlling
      for indirect fitness effects. Neutral or deleterious fitness effects of male
      killer infection should not therefore be automatically assumed. 

PMID- 23869567
TI  - Putative osmosensor--OsHK3b--a histidine kinase protein from rice shows high
      structural conservation with its ortholog AtHK1 from Arabidopsis.
AB  - Prokaryotes and eukaryotes respond to various environmental stimuli using the two
      component system (TCS). Essentially, it consists of membrane-bound histidine
      kinase (HK) which senses the stimuli and further transfers the signal to the
      response regulator, which in turn, regulates expression of various target genes.
      Recently, sequence-based genome wide analysis has been carried out in Arabidopsis
      and rice to identify all the putative members of TCS family. One of the members
      of this family i.e. AtHK1, (a putative osmosensor, hybrid-type sensory histidine
      kinase) is known to interact with AtHPt1 (phosphotransfer proteins) in
      Arabidopsis. Based on predicted rice interactome network (PRIN), the ortholog of
      AtHK1 in rice, OsHK3b, was found to be interacting with OsHPt2. The analysis of
      amino acid sequence of AtHK1 showed the presence of transmitter domain (TD) and
      receiver domain (RD), while OsHK3b showed presence of three conserved domains
      namely CHASE (signaling domain), TD, and RD. In order to elaborate on structural
      details of functional domains of hybrid-type HK and phosphotransfer proteins in
      both these genera, we have modeled them using homology modeling approach. The
      structural motifs present in various functional domains of the orthologous
      proteins were found to be highly conserved. Binding analysis of the RD domain of
      these sensory proteins in Arabidopsis and rice revealed the role of various
      residues such as histidine in HPt protein which are essential for their
      interaction. 

PMID- 23869569
TI  - Two new terpenoid benzoates with antitumor activity from the roots of Ferula
      dissecta.
AB  - Two new sesquiterpene benzoates, syreiteate A (1) and syreiteate B (2), were
      isolated from the roots of Ferula dissecta (Ledeb.) Ledeb. Their structures were
      elucidated by extensive spectroscopic methods including 1D ((1)H and (13)C) NMR,
      2D (HSQC, HMBC, DQF-COSY, and NOESY) NMR, and ESI-TOF-MS. Their configurations
      were determined on the basis of the analysis of the coupling constants, NOESY
      correlations, and circular dichroism spectrum. Compounds 1 and 2 showed potent
      growth inhibitory activity against cervical cancer HeLa cell line with the IC50
      values of 13.2 and 19.3 MUM, respectively. 

PMID- 23869570
TI  - Aza-Michael access to fluoroalkylidene analogues of biomolecules.
AB  - The synthesis of fluoroaminosulfones derived from piperidine and nucleic bases
      followed by the study of their chemical behavior in the modified Julia reaction
      are described. The resulting aminosulfones open a straightforward access to a
      series of new fluorinated biomolecules including a potent DPP-II inhibitor and
      acyclonucleoside analogues as potential enzyme inhibitors. 

PMID- 23869571
TI  - Desymmetrization of bicyclo[3.n.1]-3-one derivatives by palladium-catalyzed
      asymmetric allylic alkylation.
AB  - Desymmetrization of carbon nucleophiles by palladium-catalyzed asymmetric allylic
      alkylation has been realized for the first time. Products with three chiral
      centers were obtained in good yield and with high diastereo- and
      enantioselectivity. The method offers an efficient access to optically active
      tropane derivatives. 

PMID- 23869572
TI  - The changing face of acoustic neuroma management in the USA: analysis of the 1998
      and 2008 patient surveys from the acoustic neuroma association.
AB  - OBJECTIVE: A recent review of the national cancer center registry Surveillance
      Epidemiology and End Results (SEER) database revealed that in the United States,
      25% of Acoustic Neuromas (AN) are managed with observation. Several articles have
      questioned the aggressive treatment of these slow growing tumors. Concern has
      been raised that data from the SEER database might be biased towards treatment as
      patients who chose observation are less likely to be seen at a cancer center. To
      try and adjust for this potential bias, we decided to investigate management
      trends of AN in the United States using patient surveys conducted by the Acoustic
      Neuroma Association (ANA). Study design. Database review. METHODS: Data from the
      1998 and 2008 ANA patient's surveys were analyzed to detect trends between tumor
      size and treatment modality. Management trends including observation,
      microsurgical resection and radiation were examined as well based on tumor size
      criteria. RESULTS: During this study period, tumor size at diagnosis decreased
      significantly (1966-1998: 23.8% <= 1.5 cm; 1999-2008: 45.3% <= 1.5 cm). The use
      of microsurgery decreased from 92.7% to 53.4%, while the use of
      radiosurgery/radiotherapy increased from 5% to 24.2% and observation increased to
      22.4%. CONCLUSION: Review of data from the ANA confirmed that radiosurgery, and
      watch and wait are gaining popularity as treatment options. Regardless of this
      shift in tumor management, microsurgery continues to be the primary method of
      treatment across tumor sizes in the United States of America and observation
      remains the least common management modality.

PMID- 23869573
TI  - The Sylvian fissure, cistern and arachnoid membrane.
AB  - PURPOSE: The Sylvian (or lateral) fissure is an important structure that has both
      pathophysiological and microneurosurgical significance. The aims of this review
      were to revisit the anatomy of the Sylvian fissure and cistern and its overlying
      arachnoid membrane, and to review its role in the treatment of various surgical
      pathological lesions. METHODS: For the most part, a PubMed search was used in
      obtaining English abstracts and full-text references for this article. The
      criterion for inclusion of an article in the references for this review was that
      it included materials about the anatomical or the clinical properties of the
      Sylvian fissure, cistern and arachnoid membrane. The relevant books were also
      used in obtaining supplementary citations. RESULTS: The review presented the
      anatomy and disease states associated with the Sylvian fissure. CONCLUSIONS: A
      good knowledge of the anatomy of the Sylvian fissure, cistern and its associated
      arachnoid mater is crucial in the proper diagnosis and neurosurgical management
      of various pathological conditions.

PMID- 23869575
TI  - Motivational factors for women undergoing hysterectomy for uterine leiomyoma.

PMID- 23869574
TI  - The supraorbital keyhole approach via an eyebrow incision applied to obtain the
      olfactory bulb as a source of olfactory ensheathing cells--radiological
      feasibility study.
AB  - BACKGROUND. The purpose of the study was to test the suitability of supraorbital
      keyhole craniotomy with an eyebrow incision for obtaining olfactory bulb for
      therapeutic purposes. METHODS. Fifty three high-resolution axial head computed
      tomography images of patients with a mean age of 55 +/- 15 years were used. The
      exclusion criterion was a pathology of the anterior skull base. The virtual
      keyhole supraorbital craniotomy was placed on each side of a three-dimensional
      skull model with respect to the anatomical landmarks. Trajectories of
      neurosurgical instrument transitions to the anterior and posterior aspects of
      olfactory grooves (OGs) were subsequently designed with the use of a
      neuronavigation planning station and measured with correction allowing the
      avoidance of collisions with skull base structures. Three types of anatomical
      configuration were divided, reflecting the extent of the correction needed to
      reach the bottom of OG. RESULTS. Simulation of the surgical access and consequent
      metrological analysis was performed on 97 skull sides - 9 (8.5%) sides were
      excluded due to the large frontal sinus. The mean length of the craniotomy basis
      was 30.71 mm, lengths of the anterior and posterior trajectories were 53.25 and
      58.24 mm, respectively (p < 0.0001). In 37% of cases the value of the corrections
      exceeded the depth of OG. CONCLUSIONS. The supraorbital keyhole approach via an
      eyebrow incision may be applied to obtain the olfactory bulb as a source of
      olfactory ensheathing cells in over 60% of cases. Further verification and
      evaluation of the surgical handiness based on cadaver specimens is justifiable.

PMID- 23869576
TI  - Electronic state of oxidized nanographene edge with atomically sharp zigzag
      boundaries.
AB  - Combined scanning tunneling microscopy (STM) and density functional theory (DFT)
      characterizations of the electronic state were performed on the zigzag edge of
      oxidized nanographene samples. The oxidized zigzag edge with atomically sharp
      boundaries was prepared by electrochemical oxidation of the graphite surface in
      aqueous sulfuric acid solution. Bias-dependent STM measurements demonstrated the
      presence of the edge state at the zigzag edges with local density of states
      (LDOS) split into two peaks around the Fermi level. Our DFT-based analysis showed
      that the two-peak structure of the edge state was due to the termination of the
      zigzag edge by carbonyl functional groups. The LDOS arising from the edge states
      was slowly dampened in the bulk at the carbonyl-terminated zigzag edges (~1.5
      nm). This result is in clear contrast to the strongly localized edge states at
      hydrogenated zigzag edges in previous reports. The oxygen atoms in the carbonyl
      functional groups act as additional pi sites at the edges; thus, the topology of
      the pi electron network changes from "zigzag" to "Klein" type, leading to drastic
      modification of the edge states at the oxidized edges.

PMID- 23869577
TI  - Distinct predictors of pre- versus post-discharge venous thromboembolism after
      hepatectomy: analysis of 7621 NSQIP patients.
AB  - OBJECTIVES: Hepatectomy patients are known to be at significant risk for venous
      thromboembolism (VTE), but previous studies have not differentiated pre- versus
      post-discharge events. This study was designed to evaluate the timing, rate and
      predictors of pre- ('early') versus post-discharge ('late') VTE. METHODS: All
      patients undergoing elective hepatectomy during 2005-2010 and recorded in the
      American College of Surgeons National Surgical Quality Improvement Program
      participant use file were identified. Perioperative factors associated with 30
      day rates of early and late VTE were analysed. RESULTS: A total of 7621 patients
      underwent 4553 (59.7%) partial, 802 (10.5%) left, 1494 (19.6%) right and 772
      (10.1%) extended hepatectomies. Event rates were 1.9% for deep venous thrombosis,
      1.2% for pulmonary embolus and 2.8% for VTE. Of instances of VTE, 28.6% occurred
      post-discharge. The median time of presentation of late VTE was postoperative day
      14. Multivariate analysis determined that early VTE was associated with age >=75
      years [odds ratio (OR) 1.92, P = 0.007], male gender (OR 1.87, P = 0.002),
      intraoperative transfusion (OR 2.49, P < 0.001), operative time of >240 min (OR
      2.28, P < 0.001), organ space infection (OSI) (OR 2.60, P < 0.001), and return to
      operating room (ROR) (OR 3.25, P < 0.001). Late VTE was associated with operative
      time of >240 min (OR 2.35, P = 0.008), OSI (OR 3.78, P < 0.001) and ROR (OR 2.84,
      P = 0.011). CONCLUSIONS: Late VTE events occur in patients with clearly
      identifiable intraoperative and postoperative risk factors. This provides a
      rationale for the selective use of post-discharge VTE chemoprophylaxis in high
      risk patients.

PMID- 23869578
TI  - Processing of subliminal facial expressions of emotion: a behavioral and fMRI
      study.
AB  - The recognition of emotional facial expressions is an important means to adjust
      behavior in social interactions. As facial expressions widely differ in their
      duration and degree of expressiveness, they often manifest with short and
      transient expressions below the level of awareness. In this combined behavioral
      and fMRI study, we aimed at examining whether or not consciously accessible
      (subliminal) emotional facial expressions influence empathic judgments and which
      brain activations are related to it. We hypothesized that subliminal facial
      expressions of emotions masked with neutral expressions of the same faces induce
      an empathic processing similar to consciously accessible (supraliminal) facial
      expressions. Our behavioral data in 23 healthy subjects showed that subliminal
      emotional facial expressions of 40 ms duration affect the judgments of the
      subsequent neutral facial expressions. In the fMRI study in 12 healthy subjects
      it was found that both, supra- and subliminal emotional facial expressions shared
      a widespread network of brain areas including the fusiform gyrus, the temporo
      parietal junction, and the inferior, dorsolateral, and medial frontal cortex.
      Compared with subliminal facial expressions, supraliminal facial expressions led
      to a greater activation of left occipital and fusiform face areas. We conclude
      that masked subliminal emotional information is suited to trigger processing in
      brain areas which have been implicated in empathy and, thereby in social
      encounters. 

PMID- 23869580
TI  - Factors affecting umbilical cord blood stem cell suitability for transplantation
      in an in utero collection program.
AB  - BACKGROUND: The greatest limiting factor in the use of umbilical cord blood (UCB)
      for transplantations is the number of stem cells available in any given collected
      unit. This study examines maternal, neonatal, and obstetric factors that
      influence the suitability for banking and transplantation of UCB units collected
      in utero. STUDY DESIGN AND METHODS: This study examined 7839 UCB units collected
      in utero at two hospitals from August 1, 2008, to August 31, 2011. The variables
      were collected from cord blood records, patient charts, delivery records, and
      data processed by StemCyte, Inc. (Covina, CA), our parent bank. The mean total
      nucleated cell (TNC) count between units selected for transplant and those banked
      but not selected for transplant were also compared. RESULTS: Of the 11 variables
      evaluated, six had a significant influence on the acceptable banking TNC count of
      at least 90 * 10(7) . Of these, cord blood volume was the best predictor. The
      other variables that were predictors of the acceptable TNC count of significance
      were gestational age, infant race, parity, birthweight, and infant sex. The
      minimal bankable TNC count for banking is considerably lower than the mean TNC
      count of units actually selected for transplantation. CONCLUSION: Maternal,
      neonatal, and obstetric factors can all influence the acceptability of a cord
      blood unit collected in utero for banking. Furthermore, units with high TNC
      counts are more likely to be selected for banking. Identifying these variables in
      potential donors can likely increase the number of adequate collections.

PMID- 23869579
TI  - The role of metal nanoparticles in influencing arbuscular mycorrhizal fungi
      effects on plant growth.
AB  - A knowledge gap still remains concerning the in situ influences of nanoparticles
      on plant systems, partly due to the absence of soil microorganisms. Arbuscular
      mycorrhizal fungi (AMF) can form a mutualistic symbiosis with the roots of over
      90% of land plants. This investigation sought to reveal the responses of
      mycorrhizal clover (Trifolium repens) to silver nanoparticles (AgNPs) and iron
      oxide nanoparticles (FeONPs) along a concentration gradient of each. FeONPs at
      3.2 mg/kg significantly reduced mycorrhizal clover biomass by 34% by
      significantly reducing the glomalin content and root nutrient acquisition of AMF.
      In contrast, no negative effects of AgNPs at concentrations over 0.1 mg/kg were
      observed; however, AgNPs at 0.01 mg/kg inhibited mycorrhizal clover growth. In
      response to the elevated AgNPs content, the ability of AMF to alleviate AgNPs
      stress (via increased growth and ecological behaviors) was enhanced, which
      decreased Ag content and the activities of antioxidant enzymes in plants. These
      results were further supported by X-ray microcomputed tomography. Our findings
      suggest that in soil ecosystem, the influence of nanometals on plant systems
      would be more complicated than expected, and more attention should be focused on
      plant responses in combination with those of soil microorganisms. 

PMID- 23869581
TI  - Comment on Wille-Jorgensen et al.: Result of the implementation of
      multidisciplinary teams in rectal cancer.

PMID- 23869582
TI  - Noncrystalline-to-crystalline transformations in Pt nanoparticles.
AB  - We show that the noncrystalline-to-crystalline transition of supported Pt
      nanoparticles (NPs) in the subnanometer to nanometer size range is statistical in
      nature, and strongly affected by particle size, support, and adsorbates (here we
      use H2). Unlike in the bulk, a noncrystalline phase exists and is stable in small
      NPs, reflecting a general mesoscopic feature. Observations of >3000 particles by
      high-resolution transmission electron microscopy show a noncrystalline-to
      crystalline transition zone that is nonabrupt; there is a size regime where
      disordered and ordered NPs coexist. The NP size at which this transition occurs
      is strongly dependent on both the adsorbate and the support, and this effect is
      general for late 5d transition metals. All results are reconciled via a
      statistical description of particle-support-adsorbate interactions. 

PMID- 23869583
TI  - Increase in quantity and quality of suitable areas for invasive species as
      climate changes.
AB  - As climatically suitable range projections become increasingly used to assess
      distributions of species, we recommend systematic assessments of the quality of
      habitat in addition to the classical binary classification of habitat. We devised
      a method to assess occurrence probability, captured by a climatic suitability
      index, through which we could determine variations in the quality of potential
      habitat. This relative risk assessment circumvents the use of an arbitrary
      suitability threshold. We illustrated our method with 2 case studies on invasive
      ant species. We estimated invasion potential of the destroyer ant (Monomorium
      destructor) and the European fire ant (Myrmica rubra) on a global scale currently
      and by 2080 with climate change. We found that 21.1% of the world's landmass
      currently has a suitable climate for the destroyer ant and 16% has a suitable
      climate for European fire ant. Our climatic suitability index showed that both
      ant species would benefit from climate change, but in different ways. The size of
      the potential distribution increased by 35.8% for the destroyer ant. Meanwhile,
      the total area of potential distribution remained the same for the European fire
      ant (>0.05%), but the level of climatic suitability within this range increased
      greatly and led to an improvement in habitat quality (i.e., of invasive species'
      establishment likelihood). Either through quantity or quality of suitable areas,
      both invasive ant species are likely to increase the extent of their invasion in
      the future, following global climate change. Our results show that species may
      increase their range if either more areas become suitable or if the available
      areas present improved suitability. Studies in which an arbitrary suitability
      threshold was used may overlook changes in area quality within climatically
      suitable areas and as a result reach incorrect predictions. Incremento de la
      Cantidad y Calidad de Areas Idoneas para Especies Invasoras a Medida que Cambia
      el Clima. 

PMID- 23869585
TI  - The use of berberine for women with polycystic ovary syndrome undergoing IVF
      treatment.
AB  - OBJECTIVE: Previous studies have indicated that berberine is an effective insulin
      sensitizer with comparable activity to metformin (Diabetes 2006, 55, 2256).
      Reduced insulin sensitivity is reportedly a factor adversely affecting the
      outcome of IVF in patients with polycystic ovary syndrome (PCOS) (Human
      Reproduction 2006, 21, 1416). Our objective was to evaluate the clinical,
      metabolic and endocrine effects of berberine vs metformin in PCOS women scheduled
      for IVF treatment and to explore the potential benefits to the IVF process.
      DESIGN: We performed a prospective study in 150 infertile women with PCOS
      undergoing IVF treatment. Patients were randomized to receive berberine,
      metformin or placebo tablets for 3 months before ovarian stimulation.
      MEASUREMENTS: The clinical, endocrine, metabolic parameters and the outcome of
      IVF. RESULTS: Compared with placebo, greater reductions in total testosterone,
      free androgen index, fasting glucose, fasting insulin and HOMA-IR, and increases
      in SHBG, were observed in the berberine and metformin groups. Three months of
      treatment with berberine or metformin before the IVF cycle increased the
      pregnancy rate and reduced the incidence of severe ovarian hyperstimulation
      syndrome. Furthermore, treatment with berberine, in comparison with metformin,
      was associated with decreases in BMI, lipid parameters and total FSH requirement,
      and an increase in live birth rate with fewer gastrointestinal adverse events.
      CONCLUSIONS: Berberine and metformin treatments prior to IVF improved the
      pregnancy outcome by normalizing the clinical, endocrine and metabolic parameters
      in PCOS women. Berberine has a more pronounced therapeutic effect and achieved
      more live births with fewer side effects than metformin.

PMID- 23869584
TI  - Selective, potent blockade of the IRE1 and ATF6 pathways by 4-phenylbutyric acid
      analogues.
AB  - BACKGROUND AND PURPOSE: 4-Phenylbutyric acid (4-PBA) is a chemical chaperone that
      eliminates the accumulation of unfolded proteins in the endoplasmic reticulum
      (ER). However, its chaperoning ability is often weak and unable to attenuate the
      unfolded protein response (UPR) in vitro or in vivo. To develop more potent
      chemical chaperones, we synthesized six analogues of 4-PBA and evaluated their
      pharmacological actions on the UPR. EXPERIMENTAL APPROACH: NRK-52E cells were
      treated with ER stress inducers (tunicamycin or thapsigargin) in the presence of
      each of the 4-PBA analogues; the suppressive effects of these analogues on the
      UPR were assessed using selective indicators for individual UPR pathways. KEY
      RESULTS: 2-POAA-OMe, 2-POAA-NO2 and 2-NOAA, but not others, suppressed the
      induction of ER stress markers GRP78 and CHOP. This suppressive effect was more
      potent than that of 4-PBA. Of the three major UPR branches, the IRE1 and ATF6
      pathways were markedly blocked by these compounds, as indicated by suppression of
      XBP1 splicing, inhibition of UPRE and ERSE activation, and inhibition of JNK
      phosphorylation. Unexpectedly, however, these agents did not inhibit
      phosphorylation of PERK and eIF2alpha triggered by ER stress. These compounds
      dose-dependently inhibited the early activation of NF-kappaB in ER stress-exposed
      cells. 2-POAA-OMe and 2-POAA-NO2 also inhibited ER stress-induced phosphorylation
      of Akt. CONCLUSION AND IMPLICATIONS: The 4-PBA analogues 2-POAA-OMe, 2-POAA-NO2
      and 2-NOAA strongly inhibited activation of the IRE1 and ATF6 pathways and
      downstream pathogenic targets, including NF-kappaB and Akt, in ER stress-exposed
      cells. These compounds may be useful for therapeutic intervention in ER stress
      related pathological conditions.

PMID- 23869586
TI  - Coordinated regulation of beta-tubulin isotypes and epithelial-to-mesenchymal
      transition protein ZEB1 in breast cancer cells.
AB  - The regulation of beta-tubulin isotypes, the primary targets for antimitotic
      chemotherapeutic drugs like taxanes, has implications for drug response and drug
      resistance. Over the past 15 years, micro-RNAs have been studied widely as
      regulators of mRNA levels. For example, the tumor suppressor miR-200c was shown
      in cell culture to target mesenchymal genes, including ZEB1 [ Cochrane ( 2009 )
      Mol. Cancer Ther. 8 ( 5 ), 1055 - 1066 ]. In that work, exogenous miR-200c was
      also shown to reduce beta-tubulin class III, one of its predicted targets.
      Furthermore, decreased miR-200c and increased beta-tubulin class III were
      associated with poor outcomes for ovarian cancer patients [ Cittelly , D.M. (
      2012 ) Mol. Cancer Ther. 11 ( 12 ), 2556 - 2565 ]. Because miR-200c targets the
      epithelial-to-mesenchymal inducer ZEB1, we wanted to know whether changes in ZEB1
      parallel beta-tubulin isotype changes, implicating beta-tubulin isotypes in ZEB1
      associated cell survival pathways. We found coordinated positive feedback
      regulation of mRNA for ZEB1 and beta-tubulin isotype classes I, III, and IVB in
      MDA-MB-231 breast cancer cells, commonly used as a model for triple-negative
      breast cancers. Low levels of paclitaxel (40 nM) were found to significantly
      reduce mRNA levels for these tubulin genes along with a 2-3-fold increase in miR
      200c. ZEB1 silencing also reduced beta-tubulin isotype classes I, III, and IVB
      mRNA, whereas upregulation of ZEB1 was associated with increases in these isotype
      classes. Our work indicates that paclitaxel-induced reduction of ZEB1 and beta
      tubulin isotypes are, in part, due to increased activity of miR-200c. These
      results suggest that in aggressive breast cancers, as modeled by MDA-MB-231
      cells, beta-tubulin class III is a biomarker for cell survival mediated through
      ZEB1-induced tumor progression pathways. 

PMID- 23869587
TI  - Meta-analysis of intermittent Pringle manoeuvre versus no Pringle manoeuvre in
      elective liver surgery.
AB  - BACKGROUND AND OBJECTIVES: Intermittent Pringle manoeuvre (IPM) is frequently
      used during liver surgery. This meta-analysis aimed to review the impact on blood
      loss, operating time and morbidity and mortality with and without use of IPM.
      METHODS: An electronic search was performed of the MEDLINE, EMBASE, PubMed
      databases using both subject headings (MeSH) and truncated word searches to
      identify all articles published that related to this topic. Pooled risk ratios
      were calculated for categorical outcomes, and mean differences (MDs) for
      secondary continuous outcomes, using the fixed-effects and random-effects models
      for meta-analysis. RESULTS: Four randomized controlled trials encompassing 392
      patients were analysed to achieve a summated outcome. Pooled data analysis showed
      the use of IPM resulted in reduced transection time/cm(2) (MD -0.53 (-0.88, 
      0.18) min/cm(2) (P = 0.003)) but with comparable blood loss (mL/cm(2)) (MD -1.67
      (-4.41, 1.08) mL/cm(2), P = 0.23), overall blood loss (MD -20.42 (-89.42, 48.58)
      mL), blood transfusion requirements (risk ratio 0.78 (0.40, 1.52, P = 0.47)) and
      morbidity and mortality compared to no Pringle manoeuvre. In addition, there was
      no significant difference in the post-operative hospital stay (MD 0.37 (-0.60,
      1.34) days). CONCLUSIONS: There is no evidence that the routine use of IPM
      improves perioperative and post-operative outcomes compared to no Pringle
      manoeuvre and its routine may not be recommended.

PMID- 23869588
TI  - Views and attitudes of teachers on the educational integration of students with
      autism spectrum disorders.
AB  - OBJECTIVES: To investigate the views and attitudes of Greek teachers on
      educational and vocational integration of students with autism spectrum disorders
      (ASD). METHODS: A statistically reliable sample of questionnaires distributed
      towards a diversified teacher population is evaluated. The mean values of
      teachers' responses are analyzed with respect to critical independent variables:
      previous relevant training; and/or experience. RESULTS: The majority of the
      sample had a positive view towards the educational and vocational integration of
      students with ASD. Nevertheless, teachers appear to be sceptical in assuming that
      these students can be efficiently treated in their classroom. The vast majority
      of teachers maintain that students with ASD can be trained in technical vocation.
      However, the absence of support services is highly ranked as the most serious
      constraint for vocational integration. CONCLUSION: Training and experience
      substantially influenced teachers' views and attitudes in a positive way towards
      the integration of students with ASD.

PMID- 23869589
TI  - Hexokinase II in breast carcinoma: a potent prognostic factor associated with
      hypoxia-inducible factor-1alpha and Ki-67.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) mediates adaptive responses to
      changes under tissue hypoxia in carcinoma cells by controlling the expression of
      various target genes. Previous studies have demonstrated that HIF-1alpha is
      associated with adverse clinical outcome in breast carcinoma patients, but
      details of HIF-1alpha's role have remained largely unknown. Therefore, in this
      study, we examined the expression profiles of HIF-1alpha-induced genes in 10
      breast carcinoma cases using microarray data. As a result, we demonstrated that
      the status of hexokinase II (HKII) was associated with carcinoma recurrence in
      patients with these genes. The enzyme HKII is involved in the first, and rate
      limiting, step of glycolysis, but its clinical significance has not yet been
      examined in breast carcinoma. Therefore, we immunolocalized HKII in 118 breast
      carcinomas, and HKII immunoreactivity was detected in 44% of the cases. It is
      significantly associated with histological grade, Ki-67 labeling index and HIF
      1alpha immunoreactivity. Also, HKII status is significantly associated with
      increased risk of recurrence and adverse clinical outcome in breast cancer
      patients. Subsequent multivariate analysis demonstrated that HKII status was an
      independent prognostic factor for disease-free survival of patients. These
      results all suggest that HKII is induced by HIF-1alpha and plays important roles
      in the proliferation and/or progression of breast carcinoma possibly through
      increased glycolytic activity. The status of HKII is therefore considered a
      potent prognostic factor in human breast cancer patients.

PMID- 23869591
TI  - Phosphorylation of S344 in the calmodulin-binding domain negatively affects CCaMK
      function during bacterial and fungal symbioses.
AB  - Calcium and Ca(2+)/calmodulin-dependent protein kinase (CCaMK) plays a critical
      role in the signaling pathway that establishes root nodule symbiosis and
      arbuscular mycorrhizal symbiosis. Calcium-dependent autophosphorylation is
      central to the regulation of CCaMK, and this has been shown to promote calmodulin
      binding. Here, we report a regulatory mechanism of Medicago truncatula CCaMK
      (MtCCaMK) through autophosphorylation of S344 in the calmodulin
      binding/autoinhibitory domain. The phospho-ablative mutation S344A did not have
      significant effect on its kinase activities, and supports root nodule symbiosis
      and arbuscular mycorrhizal symbiosis, indicating that phosphorylation at this
      position is not required for establishment of symbioses. The phospho-mimic
      mutation S344D show drastically reduced calmodulin-stimulated substrate
      phosphorylation, and this coincides with a compromised interaction with
      calmodulin and its interacting partner, IPD3. Functional complementation tests
      revealed that the S344D mutation blocked root nodule symbiosis and reduced the
      mycorrhizal association. Furthermore, S344D was shown to suppress the spontaneous
      nodulation associated with a gain-of-function mutant of MtCCaMK (T271A),
      revealing that phosphorylation at S344 of MtCCaMK is adequate for shutting down
      its activity, and is epistatic over previously identified T271
      autophosphorylation. These results reveal a mechanism that enables CCaMK to 'turn
      off' its function through autophosphorylation.

PMID- 23869590
TI  - Borrelia burgdorferi oxidative stress regulator BosR directly represses
      lipoproteins primarily expressed in the tick during mammalian infection.
AB  - Differential gene expression is a key strategy adopted by the Lyme disease
      spirochaete, Borrelia burgdorferi, for adaptation and survival in the mammalian
      host and the tick vector. Many B. burgdorferi surface lipoproteins fall into two
      distinct groups according to their expression patterns: one group primarily
      expressed in the tick and the other group primarily expressed in the mammal.
      Here, we show that the Fur homologue in this bacterium, also known as Borrelia
      oxidative stress regulator (BosR), is required for repression of outer surface
      protein A (OspA) and OspD in the mammal. Furthermore, BosR binds directly to
      sequences upstream of the ospAB operon and the ospD gene through recognition of
      palindromic motifs similar to those recognized by other Fur homologues but with a
      1 bp variation in the spacer length. Putative BosR binding sites have been
      identified upstream of 156 B. burgdorferi genes. Some of these genes share the
      same expression pattern as ospA and ospD. Most notably, 12 (67%) of the 18 genes
      previously identified in a genome-wide microarray study to be most significantly
      repressed in the mammal are among the putative BosR regulon. These data indicate
      that BosR may directly repress transcription of many genes that are downregulated
      in the mammal. 

PMID- 23869592
TI  - Comparing families and staff in nursing homes and assisted living: implications
      for social work practice.
AB  - Nursing homes and residential care/assisted living settings provide care to 2.4
      million individuals. Few studies compare the experience of, and relationships
      between, family and staff in these settings, despite ongoing family involvement
      and evidence that relationships are problematic. Data from 488 families and 397
      staff members in 24 settings examined family involvement and family and staff
      burden, depressive symptoms, and perceptions; and staff absenteeism and turnover.
      There were few differences across setting types. Although conflict rarely
      occurred, there was room for improvement in family-staff relations; this area,
      and preparing family for their caregiving roles, are appropriate targets for
      social work intervention. 

PMID- 23869593
TI  - Should uterotonic agents be avoided during cesarean hysterectomy for placenta
      previa accreta?

PMID- 23869594
TI  - Temperature-driven reversible rippling and bonding of a graphene superlattice.
AB  - In order to unravel the complex interplay between substrate interactions and film
      configuration, we investigate and characterize graphene on a support with non
      three-fold symmetry, the square Ir(100). Below 500  degrees C, distinct
      physisorbed and chemisorbed graphene phases coexist on the surface, respectively
      characterized by flat and buckled morphology. They organize into alternating
      domains that extend on mesoscopic lengths, relieving the strain due to the
      different thermal expansion of film and substrate. The chemisorbed phase exhibits
      exceptionally large one-dimensional ripples with regular nanometer periodicity
      and can be reversibly transformed into physisorbed graphene in a temperature
      controlled process that involves surprisingly few C-Ir bonds. The formation and
      rupture of these bonds, rather than ripples or strain, are found to profoundly
      alter the local electronic structure, changing graphene behavior from semimetal
      to metallic type. The exploitation of such subtle interfacial changes opens new
      possibilities for tuning the properties of this unique material. 

PMID- 23869595
TI  - Subungual soft tissue chondroma with nail deformity in a child.
AB  - Soft tissue chondroma is a rare benign tumor of the cartilage. It occurs commonly
      in distal extremities of middle-aged patients. It is usually asymptomatic and
      grows slowly, making early diagnosis difficult. We report a 10-year-old patient
      with a 1-year history of a subungual soft tissue chondroma on her left fifth
      finger. The lesion arose from nail bed and distal nail matrix, resulting in nail
      dystrophy. Magnetic resonance imaging revealed a soft tissue tumor in the
      subungual region and soft tissue chondroma was diagnosed, based on
      histopathologic findings. Dermatologists should consider soft tissue chondroma in
      the differential diagnosis of subungual tumors of children. 

PMID- 23869596
TI  - Fibrillation of human serum albumin shows nonspecific coordination on
      stoichiometric increment of Copper(II).
AB  - Protein aggregation is related to a series of pathological disorders the main
      cause of which are the fibrillar species generated during the process. Human
      serum albumin (HSA) undergoes rapid fibrillation in the presence of Cu(II) at pH
      7.4 in 60% ethanol after 6-h incubation (~65  degrees C) followed by room
      temperature incubation. Here, we have investigated the effect of a stoichiometric
      variation of Cu(II) on the self-assembly of HSA using Congo red and thioflavin T
      dye-binding studies, circular dichroism spectroscopy, Fourier transform infrared
      spectroscopy, electron paramagnetic resonance spectroscopy, fluorescence
      microscopy and transmission electron microscopy. The simulation of EPR spectra
      suggests that with the increment in Cu(II) ion concentration, there is a change
      in ligand field coordination. Kinetic parameters indicate reduced cooperativity
      that may be related to the nonspecific coordination on increment of Cu(II)
      concentration. Cu(II) is also able to direct the accumulation of a large number
      of fibers along with a formation of dense fibrillar network which is evident from
      microscopic images.

PMID- 23869598
TI  - PGE-metabolite levels in CSF correlate to HIE score and outcome after perinatal
      asphyxia.
AB  - AIM: Acute anoxic exposure rapidly increases prostaglandin E2 (PGE2 ) production
      and release in neonatal mice brains. We hypothesize that PGE2 is released in
      human cerebrospinal fluid (CSF) during perinatal asphyxia and that it might be
      used as a biomarker for perinatal asphyxia. METHODS: In full-term infants with
      lumbar puncture performed within 72 h of birth (n = 35), CSF was analysed for
      prostaglandin E2 metabolite (PGEM) using an enzyme immunoassay. Term infants with
      suspected but unverified infections were used as controls (n = 11). Hypoxic
      ischaemic encephalopathy (HIE) was classified as mild, moderate or severe (HIE I
      III). Neurological assessment of surviving patients was performed at 18 months of
      age. RESULTS: Prostaglandin E2 metabolite levels correlated to a low Apgar score
      at 5 min (p < 0.01) and 10 min (p < 0.01), a low pH (p < 0.001) and HIE score (p
      < 0.05). The HIE-III cases (n = 7) had significantly higher PGEM levels compared
      with both controls and the HIE-I group (n = 8). Irrespective of HIE grade,
      patients with adverse or fatal outcome had higher PGEM values compared with
      controls and asphyxiated infants with normal outcome (p < 0.05). CONCLUSIONS:
      PGE2 is released during anoxic events in newborn infants, and PGEM may be useful
      as a biomarker for estimating degree of insult and predicting long-term outcome
      after perinatal asphyxia.

PMID- 23869597
TI  - Exploring the potential of diarylacetylenediols as hydrogen bonding catalysts.
AB  - In the course of a search for new classes of hydrogen bonding catalysts, we have
      examined diarylacetylenediols as potential catalysts for the Diels-Alder
      reaction. General and efficient methods have been developed for the preparation
      of these diols. Their structures were systematically modified, and increased
      activity was observed for those possessing an electron-withdrawing group on the
      aryl groups. The electron-deficient diarylacetylenediol catalysts, while more
      active, undergo spontaneous cyclization to the corresponding benzo[b]furans. A
      mechanism is postulated to explain this facile transformation. Computational
      studies performed on 2-ethynylphenol help to explain the effect of the alkyne on
      the conformation and hydrogen bond donating ability of the adjacent OH group.
      Finally, the crystal structure of one of the diols is reported, and it displays
      an intricate network of intermolecular hydrogen bonds. 

PMID- 23869599
TI  - A new triterpenoid saponin from Ardisia gigantifolia.
AB  - A new triterpenoid saponin, named 3-O-beta-d-glucopyranosyl-(1 -> 3)-beta-d
      xylopyranosyl-(1 -> 2)-[alpha-l-rhamnopyranosyl-(1 -> 3)]-beta-d-glucopyranosyl
      (1 -> 4)-[beta-d-glucopyranosyl-(1 -> 2)]-alpha-l-arabinopyranosyl
      3beta,16alpha,28,30-tetrahydroxy-olean-12-ene (1), along with four known
      triterpenoids (2-5), was isolated from the rhizomes of Ardisia gigantifolia.
      Their structures were elucidated by spectroscopic methods. Compounds 1-4 showed
      cytotoxic activity against Hela, EJ, BCG, and HepG-2 cell lines. The percentage
      of early apoptotic cells after treatment with 1 was significantly increased
      compared with control cells (p < 0.05). 

PMID- 23869600
TI  - Paediatric sunburn: the experience of an Australian paediatric burns unit.
AB  - AIM: The number of hospital presentations and admissions for treatment of sunburn
      remains significant, despite efforts to educate the public regarding sun
      protection. Current literature chiefly examines public health campaigns and sun
      protection behaviours and attitudes. There are very few articles that explore
      paediatric sunburn requiring hospital presentation. This study was therefore
      undertaken to provide a snapshot of this issue and to identify patterns and
      causative factors in the development of severe sunburn requiring hospital
      presentation. METHODS: Data were collected for retrospective analysis from case
      records of patients who presented with sunburn and were registered on the Burns
      Service database at the Women's and Children's Hospital in South Australia. This
      study includes patients who presented during the period of October 2006 to March
      2011. RESULTS: There were 81 cases identified over the period of 2006-2011 from
      the Burns database that had sufficient information for the purpose of this study.
      Factors such as outdoor activity and water sports were predictably apparent, with
      patients being burned on days with extremely high ultraviolet ratings. Key
      patterns that emerged were location of sunburn and sun protection use, which were
      gender and age specific. CONCLUSION: Larger-scale studies are warranted to
      further delineate the contributing factors and to identify the specific
      populations of children at risk of sunburn. Future educational programmes can
      therefore target these subgroups and behaviours for effective prevention of
      sunburn. Tailored campaigns that address these factors may be of greater impact
      in reducing hospital presentations and admissions of significant sunburn.

PMID- 23869601
TI  - Organocatalyzed anion relay leading to functionalized 2,3-dihydrofurans.
AB  - A DABCO-mediated organocatalyzed anion relay cascade based on 1
      cinnamoylcyclopropanecarboxamides has been developed and applied in the
      construction of 2,3-dihydrofurans with the original alkene and amide
      functionalities intact. In the aza-oxy-carbanion relay process, DABCO provides
      both the electron source and sink. The enolate anion-triggered ring opening of
      the cyclopropane is ascribed to the key step in the anion relay cascade. 

PMID- 23869602
TI  - In vitro measures of membrane changes reveal differences between red blood cells
      stored in saline-adenine-glucose-mannitol and AS-1 additive solutions: a paired
      study.
AB  - BACKGROUND: Saline-adenine-glucose-mannitol (SAGM) and a variant solution, AS-1,
      have been used for more than 30 years to preserve red blood cells (RBCs).
      Reputedly these RBC components have similar quality, although no paired study has
      been reported. To determine whether differences exist, a paired study of SAGM
      RBCs and AS-1 RBCs was conducted to identify membrane changes, including
      microparticle (MP) quantitation and in vitro RBC-endothelial cell (EC)
      interaction. STUDY DESIGN AND METHODS: Two whole blood packs were pooled and
      split and RBCs were prepared (n=6 pairs). One pack was suspended in SAGM and one
      in AS-1. Samples were collected during 42 days of refrigerated storage. RBC shape
      and size and glycophorin A (GPA)(+) and phosphatidylserine (PS)(+) MPs were
      measured by flow cytometry. RBC adhesion to ECs was determined by an in vitro
      flow perfusion assay. Routine variables (pH, hemolysis) were also measured.
      RESULTS: Compared to SAGM RBCs, AS-1 RBCs had lower hemolysis (p<0.04), lower
      GPA(+) MPs (p<0.03), and lower PS(+) MPs (p<0.03) from Day 14 onward. AS-1 RBCs
      had higher (p<0.02) side scatter from Day 28 onward compared to SAGM RBCs. SAGM
      RBCs were more adherent to ECs on Day 28 of storage compared to AS-1 RBCs
      (p=0.04), but reversed on Day 42 (p=0.02). CONCLUSION: SAGM RBCs lose more
      membrane during storage. SAGM RBCs had increased adherence to ECs on Day 28 of
      storage, while AS-1 RBCs were more adherent on Day 42. The effect of these
      differences on the function and survival of SAGM RBCs and AS-1 RBCs after
      transfusion remains to be determined.

PMID- 23869603
TI  - Assessing the impact of a fistula after a pancreaticoduodenectomy using the Post
      operative Morbidity Index.
AB  - BACKGROUND: The Post-operative Morbidity Index (PMI) is a quantitative utility
      measure of a complication burden created by severity weighting. The Fistula Risk
      Score (FRS) is a validated model that predicts whether a patient will develop a
      post-operative pancreatic fistula (POPF). These novel tools might provide further
      discrimination of the ISGPF grading system. METHODS: From 2001 to 2012, 1021
      pancreaticoduodenectomies were performed at four institutions. POPFs were
      categorized by ISGPF standards. PMI scores were calculated based on the Modified
      Accordion Severity Grading System. FRS scores were assigned according to the
      relative influence of four recognized factors for developing a clinically
      relevant POPF (CR-POPF). RESULTS: In total, 231 patients (22.6%) developed a
      POPF, of which 54.1% were CR-POPFs. The PMI differed significantly between the
      ISGPF grades and patients with no or non-fistulous complications (P < 0.001).
      64.9% of POPFs and 84.0% of CR-POPFs contributed the highest Accordion grade to
      the PMI. Overall, the FRS correlated well with PMI (R(2) = 0.81, P < 0.001).
      CONCLUSION: These data quantitatively reinforce the ISGPF grades that were
      developed qualitatively around the concept of clinical severity. CR-POPFs usually
      reflect the patient's highest Accordion score whereas biochemical POPFs are often
      superseded. The correlation between FRS and PMI indicates that risk factors for a
      fistula contribute to overall pancreaticoduodenectomy morbidity.

PMID- 23869604
TI  - Functional connectivity of the hippocampus in temporal lobe epilepsy: feasibility
      of a task-regressed seed-based approach.
AB  - OBJECTIVE: Resting-state functional connectivity (FC) has revealed marked network
      dysfunction in patients with temporal lobe epilepsy (TLE) compared to healthy
      controls. However, the nature and the location of these changes have not been
      fully elucidated nor confirmed by other methodologies. We assessed the presence
      of hippocampal FC changes in TLE based on the low frequency residuals of task
      related functional magnetic resonance imaging data after the removal of task
      related activation [i.e., task-regressed functional connectivity MRI (fcMRI)].
      METHOD: We employed a novel, task-regressed approach to quantify hippocampal FC,
      and compare hippocampal FC in 17 patients with unilateral TLE (9 left) with 17
      healthy controls. RESULTS: Our results suggest widespread FC reductions in the
      mesial cortex associated with the default mode network (DMN), and some local FC
      increases in the lateral portions of the right hemisphere. We found more
      pronounced FC decreases in the left hemisphere than in the right, and these FC
      decreases were greatest in patients with left TLE. Moreover, the FC reductions
      observed between the hippocampus and posterior cingulate, inferior parietal,
      paracentral regions are in agreement with previous resting state studies.
      CONCLUSIONS: Consistent with the existing literature, FC reductions in TLE appear
      widespread with prominent reductions in the medial portion of the DMN. Our data
      expand the literature by demonstrating that reductions in FC may be greatest in
      the left hemisphere and in patients with left TLE. Overall, our findings suggest
      that task-regressed FC is a viable alternative to resting state and that future
      studies may extract similar information on network connectivity from already
      existing datasets.

PMID- 23869607
TI  - Greenhouse gas implications of fleet electrification based on big data-informed
      individual travel patterns.
AB  - Environmental implications of fleet electrification highly depend on the adoption
      and utilization of electric vehicles at the individual level. Past research has
      been constrained by using aggregated data to assume all vehicles with the same
      travel pattern as the aggregated average. This neglects the inherent
      heterogeneity of individual travel behaviors and may lead to unrealistic
      estimation of environmental impacts of fleet electrification. Using "big data"
      mining techniques, this research examines real-time vehicle trajectory data for
      10,375 taxis in Beijing in one week to characterize the travel patterns of
      individual taxis. We then evaluate the impact of adopting plug-in hybrid electric
      vehicles (PHEV) in the taxi fleet on life cycle greenhouse gas emissions based on
      the characterized individual travel patterns. The results indicate that 1) the
      largest gasoline displacement (1.1 million gallons per year) can be achieved by
      adopting PHEVs with modest electric range (approximately 80 miles) with current
      battery cost, limited public charging infrastructure, and no government subsidy;
      2) reducing battery cost has the largest impact on increasing the electrification
      rate of vehicle mileage traveled (VMT), thus increasing gasoline displacement,
      followed by diversified charging opportunities; 3) government subsidies can be
      more effective to increase the VMT electrification rate and gasoline displacement
      if targeted to PHEVs with modest electric ranges (80 to 120 miles); and 4) while
      taxi fleet electrification can increase greenhouse gas emissions by up to 115
      kiloton CO2-eq per year with the current grid in Beijing, emission reduction of
      up to 36.5 kiloton CO2-eq per year can be achieved if the fuel cycle emission
      factor of electricity can be reduced to 168.7 g/km. Although the results are
      based on a specific public fleet, this study demonstrates the benefit of using
      large-scale individual-based trajectory data (big data) to better understand
      environmental implications of fleet electrification and inform better decision
      making. 

PMID- 23869608
TI  - Brachial plexopathy injury due to laparoscopic rectal surgery.

PMID- 23869605
TI  - Distinct structural alterations in proliferating cell nuclear antigen block DNA
      mismatch repair.
AB  - During DNA replication, mismatches and small loops in the DNA resulting from
      insertions or deletions are repaired by the mismatch repair (MMR) machinery.
      Proliferating cell nuclear antigen (PCNA) plays an important role in both
      mismatch-recognition and resynthesis stages of MMR. Previously, two mutant forms
      of PCNA were identified that cause defects in MMR with little, if any, other
      defects. The C22Y mutant PCNA protein completely blocks MutSalpha-dependent MMR,
      and the C81R mutant PCNA protein partially blocks both MutSalpha-dependent and
      MutSbeta-dependent MMR. In order to understand the structural and mechanistic
      basis by which these two amino acid substitutions in PCNA proteins block MMR, we
      solved the X-ray crystal structures of both mutant proteins and carried out
      further biochemical studies. We found that these amino acid substitutions lead to
      subtle, distinct structural changes in PCNA. The C22Y substitution alters the
      positions of the alpha-helices lining the central hole of the PCNA ring, whereas
      the C81R substitution creates a distortion in an extended loop near the PCNA
      subunit interface. We conclude that the structural integrity of the alpha-helices
      lining the central hole and this loop are both necessary to form productive
      complexes with MutSalpha and mismatch-containing DNA. 

PMID- 23869609
TI  - Ca(1-x)RE(x)Ag(1-y)Sb (RE = La, Ce, Pr, Nd, Sm; 0 <= x <= 1; 0 <= y <= 1):
      interesting structural transformation and enhanced high-temperature
      thermoelectric performance.
AB  - For materials used in high-temperature thermoelectric power generation, the
      choices are still quite limited. Here we demonstrate the design and synthesis of
      a new class of complex Zintl compounds, Ca(1-x)RE(x)Ag(1-y)Sb (RE = La, Ce, Pr,
      Nd, Sm) (P63mc, No. 186, LiGaGe-type), which exhibit a high figure of merit in
      the high-temperature region. Compared with the parent structure that is based on
      CaAgSb (Pnma, No. 62, TiNiSi-type), an interesting structural relationship is
      established which suggests that important size and electronic effects govern the
      formation of these multinary phases. According to theoretical calculations, such
      a structural transformation from the orthorhombic TiNiSi-type to the hexagonal
      LiGaGe-type also corresponds to an obvious modification in the electronic band
      structure, which explains the observed significant enhancement of the related
      thermoelectric properties. For an optimized p-type material,
      Ca(0.84)Ce(0.16)Ag(0.87)Sb, a figure of merit of ~0.7 can be achieved at 1079 K,
      which is comparable to that of Yb14MnSb11 at the same temperature. In addition,
      due to the excellent thermal stability and high electrical conductivity, these
      materials are very promising candidates for high-temperature thermoelectric power
      generation.

PMID- 23869610
TI  - Substance P enhanced titanium particles-induced RANKL expression in fibroblasts
      from periprosthetic membrane.
AB  - Aseptic loosening remains the primary cause of failure in total joint
      arthroplasty. Implant-derived particles are thought to be a main cause of
      osteolysis that leads to the failure. Substance P (SP) immunoreactive nerve
      fibers have been detected in the periprosthetic membrane of aseptic loose hip
      prostheses. We isolated fibroblasts from periprosthetic membrane. Fibroblasts
      were examined by real-time RT-PCR and enzyme-linked immunosorbent assay for
      expression of the receptor activator of nuclear factor kappa B ligand (RANKL),
      osteoprotegerin (OPG), cyclooxygenase (COX)-1, and COX-2. Experiments were
      performed in the presence and absence of titanium particles, SP and NS-398 (a
      selective COX-2 inhibitor). Titanium particles or SP stimulated RANKL and COX-2
      expression in fibroblasts, whereas NS-398 inhibited RANKL production, suggesting
      a COX-2-mediated event. Moreover, SP enhanced COX-2 and RANKL expression by
      titanium particles-stimulated fibroblasts. Thus, SP and titanium particles acted
      synergistically to increase RANKL expression.

PMID- 23869611
TI  - Age-related analysis of structural, biochemical and mechanical properties of the
      porcine mitral heart valve leaflets.
AB  - The aim of this study was to assess structural and biochemical differences in the
      extracellular matrix of the fetal and adult porcine mitral heart valves in
      relation to their mechanical characteristics. Using tensile tests it was
      demonstrated that the material properties of porcine mitral heart valves
      progressively change with age. The collagen content of the adult heart valve, as
      estimated by hydroxyproline assay, increases three times as compared with fetal
      heart valves. Transmission electron microscopy demonstrated that the diameter of
      collagen fibrils increased in adult heart valves compared with fetal heart
      valves. The level of collagen cross-linking is lower in the fetal heart valve
      than the adult heart valve. The reported age differences in the material
      properties of fetal and adult porcine heart valves were associated with increases
      in collagen content, the diameter of collagen fibrils and the level of collagen
      cross-linking. These data lay a foundation for systematic elucidation of the
      structural determinants of material properties of heart valves during embryonic
      and postnatal valvulogenesis. They are also essential to define the desirable
      level of tissue maturation in heart valve tissue engineering.

PMID- 23869612
TI  - Elastin turnover in malignant solid tumors.
AB  - Desmosine, a crosslinking amino acid unique to elastin, was investigated as a
      possible biomarker for cancer. Twenty-eight normal controls, median age 67 years,
      had a median value for urine desmosine of 43.5 picomoles desmosine/mg creatinine.
      The median for 19 untreated cancer subjects of similar age was significantly
      higher (175 picomoles desmosine/mg creatinine, p < 0.001). Urine desmosine levels
      in 55 subjects currently receiving chemotherapy, as well as 67 individuals who
      had survived cancer and were currently clinically disease free, were not
      significantly different from controls. Our findings indicate that elastin is
      being turned over in malignant solid tumors, releasing significantly elevated
      levels of desmosine in the urine.

PMID- 23869613
TI  - Fentanyl is less toxic on adult human mesenchymal stem cells compared to
      ropivacaine when used intraarticularly. A controlled in vitro study.
AB  - The purpose of this study was to evaluate the toxicity of ropivacaine and
      fentanyl on adult human mesenchymal stem cells (hMSC). hMSC's were seeded in
      monolayer triple-flasks and then plated into 96-well plates at a density of 5000
      cells per well. After fully aspirating the culture medium, ropivacaine or
      fentanyl in its corresponding concentration (0.5%, 0.25%, 0.125% for ropivacaine
      and 0.05%, 0.025%, 0.0125% for fentanyl) or culture medium only was added to each
      well. After 30 min, the anaesthetic was removed and fresh culture medium was
      added. hMSCs mitochondrial activity as a marker of cell proliferation and
      apoptosis marker was evaluated after 1, 24 h and 7 days. Proliferation was
      significantly decreased after a 30 min exposure to 0.5% and 0.125% ropivacaine,
      respectively compared to the control group after 24 h (p < 0.001).
      Simultaneously, apoptosis was significantly induced. Proliferation of hMSC's was
      decreased after 24 h when exposed to 0.05%, 0.025% and 0.0125% fentanyl (p <
      0.001). Apoptosis was only induced 24 h after an exposure to 0.05% fentanyl. Our
      data suggest that both drugs have a concentration-dependent effect on
      proliferation in adult hMSC's in vitro. This effect was more distinct with
      ropivacaine compared to fentanyl. Translating these results into clinical
      practice, this in vitro study suggests fentanyl as a potentially less toxic
      analgetic drug for intraarticular application after arthroscopic bone marrow
      stimulation or rotator cuff repair with comparable to prolonged pain reduction.

PMID- 23869614
TI  - Maintenance of a bone collagen phenotype by osteoblast-like cells in 3D periodic
      porous titanium (Ti-6Al-4 V) structures fabricated by selective electron beam
      melting.
AB  - Regular 3D periodic porous Ti-6Al-4 V structures were fabricated by the selective
      electron beam melting method (EBM) over a range of relative densities (0.17-0.40)
      and pore sizes (500-1500 um). Structures were seeded with human osteoblast-like
      cells (SAOS-2) and cultured for four weeks. Cells multiplied within these
      structures and extracellular matrix collagen content increased. Type I and type V
      collagens typically synthesized by osteoblasts were deposited in the newly formed
      matrix with time in culture. High magnification scanning electron microscopy
      revealed cells attached to surfaces on the interior of the structures with an
      increasingly fibrous matrix. The in-vitro results demonstrate that the novel EBM
      processed porous structures, designed to address the effect of stress-shielding,
      are conducive to osteoblast attachment, proliferation and deposition of a
      collagenous matrix characteristic of bone.

PMID- 23869615
TI  - The expanded collagen VI family: new chains and new questions.
AB  - Collagen VI is a component of the extracellular matrix of almost all connective
      tissues, including cartilage, bone, tendon, muscles and cornea, where it forms
      abundant and structurally unique microfibrils organized into different
      suprastructural assemblies. The precise role of collagen VI is not clearly
      defined although it is most abundant in the interstitial matrix of tissues and
      often found in close association with basement membranes. Three genetically
      distinct collagen VI chains, alpha1(VI), alpha2(VI) and alpha3(VI), encoded by
      the COL6A1. COL6A2 and COL6A3 genes, were first described more than 20 years ago.
      Their molecular assembly and role in congenital muscular dystrophy has been
      broadly characterized. In 2008, three additional collagen VI genes arrayed in
      tandem at a single gene locus on chromosome 3q in humans, and chromosome 9 in
      mice, were described. Following the naming scheme for collagens the new genes
      were designated COL6A4. COL6A5 and COL6A6 encoding the alpha4(VI), alpha5(VI) and
      alpha6(VI) chains, respectively. This review will focus on the current state of
      knowledge of the three new chains.

PMID- 23869616
TI  - Lumbar artificial intervertebral disc replacement: a systematic review.
AB  - BACKGROUND: Low back pain represents a significant disease burden in Australia.
      Lumbar artificial intervertebral disc replacement (AIDR) has emerged as an
      alternative surgical option to lumbar fusion for patients suffering from axial
      low back pain as a result of degenerative disc disease. OBJECTIVES: The aim of
      this review was to assess the safety and effectiveness of lumbar AIDR for
      patients suffering from significant axial back pain and/or radicular (nerve root)
      pain, secondary to disc degeneration or prolapse, who have failed non-operative
      treatment. METHODS: A systematic search of several electronic databases was
      conducted between January 2005 and April 2012 to identify relevant randomized
      controlled trials and non-randomized comparative studies. Inclusion of studies
      was established through the application of a predetermined protocol by two
      independent reviewers. RESULTS: Six randomized controlled trials (comprising nine
      studies) and one non-randomized comparative study comparing lumbar AIDR with
      lumbar fusion were included in this review. For the majority of adverse events
      reported, there were no obvious differences in incidence rates between the two
      treatment groups, and serious adverse events were rare in both groups. Following
      lumbar AIDR, effectiveness outcomes including Oswestry Disability Index scores,
      procedural success rates, pain scores, narcotic medication use and patient
      satisfaction were generally significantly better than, or equivalent to, outcomes
      achieved following lumbar fusion. CONCLUSIONS: In the short to medium term, the
      safety and effectiveness of lumbar AIDR appears to be comparable to that of
      lumbar fusion.

PMID- 23869617
TI  - The effects of hoarding disorder on families: an integrative review.
AB  - Compulsive hoarding affects approximately 2-5% of the adult population.
      Increasing recognition has led to its inclusion as a distinct condition in
      forthcoming revisions to the Diagnostic and Statistical Manual V. Hoarding
      behaviour can have a detrimental effect on the health and well-being of family
      members. A rigorous review of available evidence using a novel three-stage
      literature search was undertaken: (1) an extensive scoping review; (2) a
      traditional search of databases including Cumulative Index to Nursing and Allied
      Health Literature, Medical Literature Analysis and Retrieval System Online, and
      psycINFO using combinations of keywords; and (3) review of cited references and
      hand-searching of selected journals. Evidence was selected using predefined
      inclusion criteria. Papers included two surveys, one qualitative study and one
      case study. An integrative review methodology was used to synthesize the evidence
      presented. Analysis revealed three overriding themes: quality of life, shattered
      families and rallying around. These illuminated the experiences of family
      members. These papers revealed families under strain and often at breaking point
      but with the resolve to pull together if the right support is available. This
      review concludes that further research is needed to investigate the effects of
      hoarding on family members and how these may best be met.

PMID- 23869618
TI  - A novel androgen signalling pathway uses dihydrotestosterone, but not
      testosterone, to activate the EGF receptor signalling cascade in prostate stromal
      cells.
AB  - BACKGROUND AND PURPOSE: Human prostate growth and function are tightly controlled
      by androgens that are generally thought to exert their effects by regulating gene
      transcription. However, a rapid, non-genomic steroid action, often involving an
      elevation of intracellular calcium ([Ca(2+) ]i ), has also been described in a
      number of cell types. In this study we investigate whether androgens acutely
      regulate [Ca(2+) ]i in stromal cells derived from the human prostate.
      EXPERIMENTAL APPROACH: Human-cultured prostatic stromal cells (HCPSCs) were
      loaded with the calcium-sensitive fluorophore, fura-2-acetoxymethyl ester (FURA
      2AM) (10 MUM). Changes in [Ca(2+) ]i in response to the androgens,
      dihydrotestosterone (DHT) and testosterone, as well as EGF were measured by
      fluorescence microscopy. KEY RESULTS: DHT, but not testosterone (0.03-300 nM),
      elicited concentration-dependent elevations of [Ca(2+) ]i within 1 min of
      addition. These responses were blocked by the androgen receptor antagonist,
      flutamide (10 MUM); the sarcoplasmic reticulum ATPase pump inhibitor,
      thapsigargin (1 MUM); the inositol trisphosphate receptor inhibitor, 2
      aminoethyldiphenyl borate (50 MUM) and the PLC inhibitor, U-73122 (1 MUM).
      Responses were also blocked by the L-type calcium channel blocker, nifedipine (1
      MUM), and by removal of extracellular calcium. A similar transient elevation of
      [Ca(2+) ]i was elicited by EGF (100 ng.mL(-1) ). The EGF receptor inhibitor, AG
      1478 (30 nM), and the MMP inhibitor, marimastat (100 nM), blocked the DHT-induced
      elevation of [Ca(2+) ]i . CONCLUSIONS AND IMPLICATIONS: These studies show that
      DHT elicits an androgen receptor-dependent acute elevation of [Ca(2+) ]i in
      HCPSC, most likely by activating EGF receptor signalling.

PMID- 23869619
TI  - Guanfacine-induced lichenoid drug eruption in a child with autism and attention
      deficit hyperactivity disorder.
AB  - Lichenoid drug eruptions (LDEs) have a variety of medication causes. We report a
      case of a 5-year-old boy with autism and attention deficit hyperactivity disorder
      treated with guanfacine who developed pruritic lesions consistent with LDEs.
      Rechallenge was not attempted. There are several clinical and histopathologic
      clues that may distinguish LDEs from lichen planus. 

PMID- 23869620
TI  - Role of glutamate receptors in the dorsal reticular nucleus in formalin-induced
      secondary allodynia.
AB  - The role of glutamate receptors present in the medullary dorsal reticular nucleus
      (DRt) in the formalin test and formalin-induced secondary nociception was studied
      in rats. Secondary mechanical allodynia was assessed with von Frey filaments
      applied to the rat's hindpaw, and secondary thermal hyperalgesia was evaluated
      with the tail-immersion test. The selective glutamate receptor antagonists MK801
      (N-methyl-D-aspartate receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) (AMPA/KA receptor antagonist) and A841720 (metabotropic glutamate 1
      receptor antagonist) were injected into the DRt before or 6 days after formalin
      injection in the rat. In the formalin test, the three antagonists significantly
      reduced the number of flinches in both phases of the test. DRt microinjection of
      MK801 or A841720, but not of CNQX, reduced both secondary nociceptive behaviors.
      Moreover, pre-treatment with the three antagonists injected into the DRt
      prevented the development of secondary mechanical allodynia and secondary thermal
      hyperalgesia. Similarly, in these rats, the number of c-Fos-like immunoreactive
      neurons were markedly reduced in both the superficial and deep lamina of the
      dorsal horn. Our findings support the role of DRt as a pain facilitator in acute
      and chronic pain states, and suggest a key role of glutamate receptors during the
      development and maintenance of formalin-induced secondary allodynia.

PMID- 23869621
TI  - Lichen conservation in heavily managed boreal forests.
AB  - Lichens are an important component of the boreal forest, where they are long
      lived, tend to accumulate in older stands, and are a major food source for the
      threatened woodland caribou (Rangifer tarandus caribou). To be fully sustainable,
      silvicultural practices in the boreal forest must include the conservation of
      ecological integrity. Dominant forest management practices, however, have short
      term negative effects on lichen diversity, particularly the application of
      herbicides. To better understand the long-term effects of forest management, we
      examined lichen regeneration in 35 mixed black spruce (Picea mariana) and jack
      pine (Pinus banksiana) forest stands across northern Ontario to determine
      recovery following logging and postharvest silvicultural practices. Our forest
      stands were 25-40 years old and had undergone 3 common sivilcultural treatments
      that included harvested and planted; harvested, planted, and treated with N
      [phosphonomethyl] glycine (glyphosate); and harvested, planted, and treated with
      2,4-dichlorophenoxyacetic acid (2,4-D). Forest stands with herbicide treatments
      had lower lichen biomass and higher beta and gamma diversity than planted stands
      that were not treated chemically or control stands. In northwestern Ontario,
      planted stands that were not treated chemically had significantly greater (p <
      0.05) alpha diversity than stands treated with herbicides or control stands. Our
      results show that common silvicultural practices do not emulate natural
      disturbances caused by wildfires in the boreal forest for the lichen community.
      We suggest a reduction in the amount of chemical application be considered in
      areas where lichen biomass is likely to be high and where the recovery of
      woodland caribou is an objective.

PMID- 23869622
TI  - Quantification of long-term effects of botulinum injection in a case of cerebral
      palsy affecting the upper limb movement.
AB  - OBJECTIVE: The aim of this work was to put into evidence the long-lasting
      modification induced by botulinum toxin injection and rehabilitative treatment on
      motor control. METHODS: In this contribution, we report the case of a female
      child showing hemiplegia, due to cerebral palsy. She underwent botulinum
      injection, followed by physical and occupational therapy. We quantified the
      biomechanical, cerebral and occupational aspects of her impaired upper limb, also
      dynamically, with respect to her pre- and post-treatment condition. RESULTS:
      Small long-lasting improvements--induced on biomechanics by botulinum injection-
      triggered wide cerebral modification, well reflected in improved contextual
      movements and motor strategy. CONCLUSION: These results provide evidences that
      small modifications in the end-effector performance often imply cerebral
      modifications and improvement in finalized motor strategy.

PMID- 23869623
TI  - Electrochemical nanostructuring of n-GaAs photoelectrodes.
AB  - Methods to simultaneously optimize carrier collection and light in-coupling in
      semiconductors are important for developing low-cost, high-efficiency
      photovoltaics and photoelectrodes. We anodically etched nanostructures into
      planar (100) n-GaAs wafers with different bulk minority carrier diffusion lengths
      L(D). The structures were varied by changing the anodization parameters. A
      ferrocene/ferrocenium electrolyte provided a conformal rectifying contact to the
      anodized n-GaAs and enabled the measurement of carrier generation and collection
      as a function of nanostructure geometry and L(D). Internal quantum efficiency
      Phi(int) of photoelectrodes varied with nanostructure geometry and L(D). External
      quantum efficiency Phi(ext) also depended on the reflectance of the
      nanostructured GaAs-electrolyte interface. Reflectance was minimized using
      anodization current densities of 100-150 mA cm(-2), which etched subwavelength
      trigonal prismatic nanostructures ~400 nm in width at their base. For Si-doped n
      GaAs with L(D) = 170 nm, peak Phi(ext) of ~75% and Phi(int) of ~85% was achieved
      using J(anod) = 150 mA cm(-2). The control of both surface nanostructure (to
      minimize reflection) and pore depth and spacing (to optimize 3D carrier
      collection) via two-step anodization yielded photoelectrodes with peak Phi(ext)
      of ~85% and peak Phi(int) of ~95% for Te-doped n-GaAs with a bulk L(D) of only
      420 nm. The measured short-circuit current densities for the nanostructured
      photoelectrodes were up to 2.5 times that of planar controls, demonstrating that
      appropriate nanostructuring significantly improves carrier collection even for
      direct bandgap materials with large absorption coefficients like GaAs.

PMID- 23869624
TI  - Complex care needs of patients with late-stage HIV disease: a retrospective
      study.
AB  - This retrospective chart review provides a profile of an emerging population of
      vulnerable HIV patients with complex comorbidities. Data were abstracted from all
      83 patients admitted in 2008 to Casey House, a community-based hospital dedicated
      to supportive and palliative care for persons with HIV in Toronto, Canada. We
      describe patient characteristics, including medical and psychiatric conditions,
      and use a Venn diagram and case study to illustrate the frequency and reality of
      co-occurring conditions that contribute to the complexity of patients' health and
      health care needs. The mean age at admission was 49.2 years (SD10.5). Sixty-seven
      patients (80.7%) were male. Patients experienced a mean of 5.9 medical
      comorbidities (SD2.3) and 1.9 psychiatric disorders (lifetime Axis I diagnoses).
      Forty patients (48.2%) experienced cognitive impairment including HIV-associated
      dementia. Patients were on a mean of 11.5 (SD5.3) medications at admission; 74.7%
      were on antiretroviral medications with 55.0% reporting full adherence. Current
      alcohol and drug use was common with 50.6% reporting active use at admission. Our
      Venn diagram illustrates the breadth of complexity in the clients with 8.4% of
      clients living in unstable housing with three or more medical comorbidities and
      two or more psychiatric diagnoses. Comprehensive HIV program planning should
      include interventions that can flexibly adapt to meet the multidimensional and
      complex needs of this segment of patients. Researchers, policy-makers, and
      clinicians need to have greater awareness of overlapping medical, psychiatric and
      psychosocial comorbidities. Inclusion of the needs of these most vulnerable
      patients in the development of evidence-based guidelines is an important step for
      effectively treating, preventing, and planning for the future of HIV/AIDS care.

PMID- 23869625
TI  - Shifts in the evolutionary rate and intensity of purifying selection between two
      Brassica genomes revealed by analyses of orthologous transposons and relics of a
      whole genome triplication.
AB  - Recent sequencing of the Brassica rapa and Brassica oleracea genomes revealed
      extremely contrasting genomic features such as the abundance and distribution of
      transposable elements between the two genomes. However, whether and how these
      structural differentiations may have influenced the evolutionary rates of the two
      genomes since their split from a common ancestor are unknown. Here, we
      investigated and compared the rates of nucleotide substitution between two long
      terminal repeats (LTRs) of individual orthologous LTR-retrotransposons, the rates
      of synonymous and non-synonymous substitution among triplicated genes retained in
      both genomes from a shared whole genome triplication event, and the rates of
      genetic recombination estimated/deduced by the comparison of physical and genetic
      distances along chromosomes and ratios of solo LTRs to intact elements. Overall,
      LTR sequences and genic sequences showed more rapid nucleotide substitution in B.
      rapa than in B. oleracea. Synonymous substitution of triplicated genes retained
      from a shared whole genome triplication was detected at higher rates in B. rapa
      than in B. oleracea. Interestingly, non-synonymous substitution was observed at
      lower rates in the former than in the latter, indicating shifted densities of
      purifying selection between the two genomes. In addition to evolutionary
      asymmetry, orthologous genes differentially regulated and/or disrupted by
      transposable elements between the two genomes were also characterized. Our
      analyses suggest that local genomic and epigenomic features, such as
      recombination rates and chromatin dynamics reshaped by independent proliferation
      of transposable elements and elimination between the two genomes, are perhaps
      partially the causes and partially the outcomes of the observed inter-specific
      asymmetric evolution.

PMID- 23869626
TI  - Climatic stress increases forest fire severity across the western United States.
AB  - Pervasive warming can lead to chronic stress on forest trees, which may
      contribute to mortality resulting from fire-caused injuries. Longitudinal
      analyses of forest plots from across the western US show that high pre-fire
      climatic water deficit was related to increased post-fire tree mortality
      probabilities. This relationship between climate and fire was present after
      accounting for fire defences and injuries, and appeared to influence the effects
      of crown and stem injuries. Climate and fire interactions did not vary
      substantially across geographical regions, major genera and tree sizes. Our
      findings support recent physiological evidence showing that both drought and
      heating from fire can impair xylem conductivity. Warming trends have been linked
      to increasing probabilities of severe fire weather and fire spread; our results
      suggest that warming may also increase forest fire severity (the number of trees
      killed) independent of fire intensity (the amount of heat released during a
      fire). 

PMID- 23869627
TI  - A notational analysis of shot characteristics in top-level table tennis players.
AB  - This study aimed to analyse selected shot characteristics in top-level table
      tennis matches, with a special focus on comparing the playing style of Asian and
      European players. Ten men's matches played by 20 top-ranked players (14 Asians
      and 6 Europeans) were analysed. The indicators examined were the area of ball
      bouncing for serves (n =918), and the stroke type, footwork type and shot outcome
      for other shots (n=3692). The interrelationships between variables were analysed
      using chi-squared tests, log-linear modelling and multiple correspondence
      analysis. A strong association was found between strokes and footwork types, with
      most stroke types executed each after specific footwork types. Furthermore, a
      clear tendency to have a positive, negative or neutral outcome was observed for
      each stroke type. When compared to Europeans, Asians used more frequently the
      most aggressive strokes and footwork types, confirming anecdotal claims on their
      particularly offensive playing style. Asians showed also a better serving
      effectiveness, often sending the ball in those areas of the table from which a
      counterattack is difficult to make. In summary, this study gives a systematic
      description of highly relevant technical and tactical characteristics in top
      level table tennis, thus providing valuable information for coaches and
      performance analysts.

PMID- 23869628
TI  - Predicting the risks of venous thromboembolism versus post-pancreatectomy
      haemorrhage: analysis of 13,771 NSQIP patients.
AB  - BACKGROUND: The fear of an early post-pancreatectomy haemorrhage (PPH) may
      prevent surgeons from prescribing post-operative venous thromboembolism (VTE)
      chemoprophylaxis. The primary hypothesis of this study was that the national post
      pancreatectomy early PPH rate was lower than the rate of VTE. The secondary
      hypothesis was that patients at high risk for post-discharge VTE could be
      identified, potentially facilitating the selective use of extended
      chemoprophylaxis. PATIENTS AND METHODS: All elective pancreatectomies were
      identified in the 2005 to 2010 American College of Surgeons-National Surgical
      Quality Improvement Program (ACS-NSQIP) database. Factors associated with 30-day
      rates of (pre- versus post-discharge) VTE, early PPH (transfusions > 4 units
      within 72 h) and return to the operating room (ROR) with PPH were analysed.
      RESULTS: Pancreaticoduodenectomies (PD) and distal pancreatectomies (DP) numbered
      9140 (66.4%) and 4631 (33.6%) out of 13 771 pancreatectomies, respectively. Event
      rates included: VTE (3.1%), PPH (1.1%) and ROR+PPH (0.7%). PD and DP had similar
      VTE rates (P > 0.05) with 31.9% of VTE occurring post-discharge. Independent risk
      factors for late VTE included obesity [odds ratio (OR), 1.5], age >= 75 years
      (OR, 1.8), DP (OR, 2.4) and organ space infection (OR, 2.1) (all P < 0.02).
      CONCLUSIONS: Within current practice patterns, post-pancreatectomy VTE outnumber
      early haemorrhagic complications, which are rare. The fear of PPH should not
      prevent routine and timely post-pancreatectomy VTE chemoprophylaxis. Because one
      third of VTE occur post-discharge, high-risk patients may benefit from post
      discharge chemoprophylaxis.

PMID- 23869629
TI  - Salivary biomarkers: relationship between oxidative stress and alveolar bone loss
      in chronic periodontitis.
AB  - OBJECTIVES: Oxidative stress is implicated in the pathogenesis of many systemic
      and oral diseases such as periodontal disease. The main aim of this study is to
      explore a possible association between salivary markers of OS and alveolar bone
      loss. MATERIALS AND METHODS: The study included 20 patients with chronic
      periodontitis and 20 controls. Salivary OS biomarkers 8-hidroxy-desoxguanosine (8
      HOdG), malondialdehyde (MDA), uric acid, total antioxidant capacity (TAC) and
      glutathione peroxidase (GPx) were evaluated. Bone loss markers such as C-terminal
      telopeptide of type I collagen (CTX I), matrix metalloproteinases-8 (MMP-8),
      osteocalcin and 25-hydroxy vitamin D3 (25- OH D) were detected in this study. The
      methods included general biochemical tests and ELISA. RESULTS: Salivary 8-OHdG,
      MDA levels were significantly higher in the chronic periodontitis group compared
      with controls (p < 0.05). Salivary activities for uric acid, TAC and GPx were
      significantly decreased in patients with chronic periodontitis vs controls (p <
      0.05). Salivary levels for CTX I, MMP-8, 25-OH D and Osteocalcin were
      significantly higher in the chronic periodontitis group compared to the controls
      (p < 0.05). A significant positive correlation was observed between salivary
      levels of MDA and CTX I. Significant negative correlations between uric acid and
      CTX I and between MMP-8 and uric acid have been found. Significant positive
      correlations were observed between CTX I, MMP-8, 25-OH D, osteocalcin and
      clinical parameters of periodontal disease. CONCLUSIONS: Important oxidative
      stress associated with alveolar bone loss biomarkers can be detected in saliva of
      patients with periodontal disease.

PMID- 23869630
TI  - Management of placenta accreta.
AB  - Cesarean hysterectomy is considered the reference standard treatment for placenta
      accreta. In young women who want the option of future pregnancy and agree to
      close follow-up monitoring, conservative treatment is a valid option. Several key
      points of both cesarean hysterectomy and conservative treatment remain debatable,
      such as timing of delivery, attempted removal of the placenta, use of temporal
      internal iliac occlusion balloon catheters, ureteral stents, prophylactic
      embolization, and methotrexate. In cases of placenta percreta with bladder
      involvement, conservative treatment may be the optimal management. Regardless of
      the chosen option, the woman and her partner should be warned of the high risk of
      maternal complications related to an abnormally invasive placenta. 

PMID- 23869632
TI  - Using the ADDIE model in designing library instruction.
AB  - Librarians are increasingly placed in the role of instructor and are required to
      design and deliver effective instruction. This article highlights ADDIE, an
      instructional design model that librarians at Weill Cornell Medical College used
      to redesign an evidence-based medicine course taken by first-year medical
      students. The ADDIE model incorporates the five phases of analysis, design,
      development, implementation, and evaluation. It was found that the application of
      ADDIE can result in instruction that focuses on learning outcomes relevant to
      students, meets students' needs, and facilitates active learning. 

PMID- 23869631
TI  - Building and evaluating an informatics tool to facilitate analysis of a
      biomedical literature search service in an academic medical center library.
AB  - This study utilizes an informatics tool to analyze a robust literature search
      service in an academic medical center library. Structured interviews with
      librarians were conducted focusing on the benefits of such a tool, expectations
      for performance, and visual layout preferences. The resulting application
      utilizes Microsoft SQL Server and .Net Framework 3.5 technologies, allowing for
      the use of a web interface. Customer tables and MeSH terms are included. The
      National Library of Medicine MeSH database and entry terms for each heading are
      incorporated, resulting in functionality similar to searching the MeSH database
      through PubMed. Data reports will facilitate analysis of the search service. 

PMID- 23869633
TI  - Sustaining librarian vitality: embedded librarianship model for health sciences
      libraries.
AB  - With biomedical information widely accessible from anywhere at any time, health
      sciences libraries have become less centralized, and they are challenged to stay
      relevant and vital to the mission and strategic goals of their home institution.
      One solution is to embed librarians at strategic points in health professions'
      education, research, and patient care. This article discusses a proposed five
      level model of embedded librarianship within the context of health sciences
      libraries and describes different roles, knowledge, and skills desirable for
      health sciences librarians working as embedded librarians. 

PMID- 23869634
TI  - Using NLM exhibits and events to engage library users and reach the community.
AB  - In an effort to reach out to library users and make the library a more relevant,
      welcoming place, the University of Florida's Health Science Center Library hosted
      exhibits from the National Library of Medicine's (NLM) Traveling Exhibition
      Program. From 2010 through 2012, the library hosted four NLM exhibits and created
      event series for each. Through reflection and use of a participant survey,
      lessons were learned concerning creating relevant programs, marketing events, and
      forming new partnerships. Each successive exhibit added events and activities to
      address different audiences. A survey of libraries that have hosted NLM exhibits
      highlights lessons learned at those institutions. 

PMID- 23869635
TI  - Lessons learned: year-by-year improvement of a required information competency
      course.
AB  - At the Ohio State University, a health sciences librarian is the co-instructor in
      a required information competencies course for first-year undergraduate students
      in the Honors Biomedical Science Major. This article discusses the creation and
      development of the credit-bearing, in-person course from the curriculum planning
      phase in 2005 to present. Improvements to the course are described by year.
      Student feedback, student performance, and reflection by the co-instructors
      influenced the course improvements, including changes in content, delivery,
      student feedback mechanisms, and assessment of student learning. The course
      teaches students to access, organize, read, and analyze the biomedical research
      literature. 

PMID- 23869636
TI  - Efficacy of screen-capture tutorials in literature search training: a pilot study
      of a research method.
AB  - This pilot study evaluated a research method for examining the efficacy of screen
      capture tutorials in teaching database search skills. This is not a results
      oriented paper but rather describes the facets and testing of a mixed methods
      protocol. The lessons learned can be applied to a result-oriented study with a
      larger sample size and to the development of methods for similar studies. The
      protocol tried to balance control of variables with observing behavior in the
      natural setting. A combination of concept maps, an information stage
      questionnaire, and screen recordings provided rich information about health
      practitioners' research questions and search strategies. 

PMID- 23869637
TI  - A preliminary analysis of library holdings as compared to the basic resources for
      pharmacy education list.
AB  - The catalogs of 11 university libraries were analyzed against the Basic Resources
      for Pharmaceutical Education (BRPE) to measure the percent coverage of the core
      total list as well as the core sublist. There is no clear trend in this data to
      link school age, size, or rank with percentage of coverage of the total list or
      the "First Purchase" core list when treated as independent variables.
      Approximately half of the schools have significantly higher percentages of core
      titles than statistically expected. Based on this data, it is difficult to
      predict what percentage of titles on the BRPE a library will contain. 

PMID- 23869638
TI  - AgeLine: a database of social gerontology literature.
AB  - AgeLine, an EBSCO host database, focuses on literature on topics relating to
      people over the age of 50. AgeLine is geared to professionals in aging-related
      fields, such as health care professionals, social workers, and caregivers, as
      well as consumers. This column includes a sample search and a discussion of
      additional AgeLine features.

PMID- 23869639
TI  - Near field communication: getting in touch with mobile users.
AB  - Near field communication is a method for sending and receiving small amounts of
      data across very short distances wirelessly. This technology is already available
      in a number of mobile devices and has many possible uses, including electronic
      payment, access control, and information exchange. This article will explain the
      basic principles of near field communication, discuss some of the ways it can be
      used in libraries, and explore some possible concerns with the technology. A list
      of resources for additional information is also included. 

PMID- 23869640
TI  - Invite yourself to the table: librarian contributions to the electronic medical
      record.
AB  - Librarians from Exempla Healthcare hospitals initiated contact with the chief
      medical information officer regarding evidence-based medicine activities related
      to the development of the system's Electronic Medical Record (EMR). This column
      reviews the librarians' involvement in specific initiatives that included
      providing comparative information on point-of-care resources to integrate into
      the EMR, providing evidence as needed for the order sets being developed, and
      participating with clinicians on an evidence-based advisory committee. 

PMID- 23869641
TI  - Strategies for data management engagement.
AB  - The research landscape is growing dramatically, and librarians are examining new
      roles, services, and types of collaborations to support data-intensive research.
      This column describes curricular enhancements at one School of Library and
      Information Science in the United States. Several key areas of data management in
      which health sciences librarians may wish to build or enhance their skills are
      outlined. Possible roles and opportunities for health sciences librarians to
      strategically engage in data management initiatives are also presented. 

PMID- 23869646
TI  - Multichromophoric arrays arranged around a triptycene scaffold: synthesis and
      photophysics.
AB  - Here we report on the synthesis, characterization, and photophysics of
      multichromophoric arrays based on a triptycene scaffold that acts as a bridging
      ligand for Ir(III) and Os(II) satellite active components. The triptycene
      scaffold not only furnishes a rigid star-shaped 3D displacement of the metallic
      units in space but also plays an active role in the energy cascade. The
      transition metal complexes have been designed in order to display an ideal
      cascade in their lowest excited state energy levels. For this purpose, a novel
      Ir(III) complex containing two dbpz (dibenzo[a,c]phenazine) ligands (Ir) has been
      synthesized. The key step in the synthesis of the array was the final cross
      coupling between the mixed complex IrF-Os and Ir, providing the target
      heterotrinuclear complex IrF-Ir-Os. The photophysical properties of models
      confirmed the appropriate energy displacement of the single chosen active units,
      in the order triptycene > IrF > Ir > Os, and fast and efficient energy transfer
      processes leading to the final population of the Os-based triplet level have been
      evidenced. The reported arrays can be considered as efficient antenna systems
      with an absorption range extending up to 700 nm, where the triptycene bridging
      ligand provides both a structural and a photophysical function. 

PMID- 23869647
TI  - Utility and cost of low-vacuum reinfusion drains in patients undergoing surgery
      for subcapital hip fracture repair. A before and after cohort study.
AB  - BACKGROUND: Postoperative blood loss may be a risk factor for allogeneic blood
      transfusion (ABT) in patients undergoing subcapital hip fracture (SHF) repair. We
      investigated the utility and costs of using a low-vacuum reinfusion drain
      (Bellovac ABT) within a blood management protocol for reducing ABT requirements
      in consecutive SHF. METHODS: The blood management protocol consisted of the
      application of a restrictive transfusion trigger (Hb < 8 g/dl), the peri
      operative administration of IV iron sucrose (3 * 200 mg/48 h) +/- recombinant
      erythropoietin (1 * 40 000 IU sc) and the use of Bellovac ABT (Group 2, n = 117).
      An immediate previous SHF series managed without Bellovac ABT served as control
      (Group 1, n = 138). RESULTS: Overall, 72 out of 255 (28%) received at least one
      ABT unit (2.1 +/- 1.0 U/transfused patient) without differences between groups.
      However, in the subgroup of patients with admission Hb < 13 g/dl, the use of
      Bellovac ABT reduced postoperative ABT rates (16% vs. 46%, for groups 2 and 1,
      respectively; P = 0.001), although only 3 were reinfused, and was cost-saving.
      The use of Bellovac ABT also resulted in fewer wound bleeding complications, but
      there were no differences in Hb at postoperative days 7 and 30 between groups.
      CONCLUSIONS: In SHF patients with admission Hb < 13 g/dl and managed with peri
      operative IV iron +/- recombinant erythropoietin plus restrictive transfusion
      indication, the use of Bellovac ABT was associated with reduced ABT requirements,
      without increasing postoperative complications, and cost-savings.

PMID- 23869648
TI  - Successful medical treatment for globe penetration following tooth extraction in
      a dog.
AB  - A five-year-old entire male Tibetan Terrier was referred for left-sided
      periorbital swelling and blepharospasm 4 days following ipsilateral maxillary
      tooth extraction. Examination of the left eye revealed mild exophthalmos, pain on
      retropulsion, and absent menace response and pupillary light reflexes.
      Examination of the posterior segment was not possible owing to the anterior
      segment pathology. Differential diagnoses considered were iatrogenic globe
      penetration and peribulbar abscess/cellulitis. Ocular ultrasound was consistent
      with a penetrating wound to the globe. Treatment with systemic prednisolone and
      marbofloxacin, and topical atropine sulfate 1%, prednisolone acetate, and
      brinzolamide was started. Marked clinical improvement allowed visual confirmation
      of the perforation. Oral prednisolone was tapered over the following 10 weeks. At
      final re-examination (10 months), the patient was visual, and fundic examination
      revealed an additional chorioretinal scar, most likely an exit wound that was
      obscured by vitreal debris on initial examinations. Neither scar was associated
      with retinal detachment. To the authors' knowledge, this is the first reported
      case of successful medical management of iatrogenic globe penetration following
      exodontic procedures.

PMID- 23869649
TI  - Total synthesis and antibacterial screening of ( +/- )-7-butyl-6,8-dihydroxy-3
      pentyl-3,4-dihydroisochromen-1-one.
AB  - A new total synthesis of ( +/- )-7-butyl-6,8-dihydroxy-3-pentyl-3,4
      dihydroisochromen-1-one, isolated as R-enantiomer from Geotrichum sp., has been
      described. Reaction of 4-butyl-3,5-dimethoxyhomophthalic anhydride with hexanoyl
      chloride in the presence of 1,1,3,3-tetramethyl guanidine and triethyl amine
      afforded 7-butyl-6,8-dimethoxy-3-pentylisochromen-1-one, which was converted into
      corresponding 3,4-dihydroisochromen-1-one by successive ring opening and
      reduction. Final demethylation to furnish the natural product was achieved using
      anhydrous aluminum chloride in ethanethiol. The target compound and the
      intermediates were subjected to antibacterial evaluation against 10 bacterial
      strains using levofloxacin as standard. 

PMID- 23869650
TI  - The initial feasibility of a computer-based motivational intervention for
      adherence for youth newly recommended to start antiretroviral treatment.
AB  - Young people represent the largest number of new HIV infections, thus youth
      living with HIV (YLH) are likely to be the largest group to initiate
      antiretroviral treatment (ART). Adherence patterns for behaviorally infected YLH
      are not adequate to effectively manage the disease; therefore, novel
      interventions are needed to improve medication adherence. The purpose of the
      current study, which will precede a randomized controlled trial, was to assess
      the initial feasibility of an individually tailored computer-based two-session
      interactive motivational interviewing (MI) intervention for YLH newly recommended
      to start ART. Intervention development occurred in collaboration with three youth
      advisory groups. Ten youth (ages 18-24) were recruited to participate in this
      study. Participants completed the intervention online. Intervention components
      focused on medication adherence (rating perceived importance and confidence, and
      goal setting). Retention was 100% for both intervention sessions. All
      participants (n=10) felt medication adherence was important, but 80% felt
      confident they could manage their adherence to HIV medications. Ninety percent of
      participants set the goal of taking their HIV medications exactly as prescribed
      and reported success achieving this goal at follow-up. Additionally, participants
      were satisfied with the quality of the sessions and the amount of assistance they
      received for managing their adherence to HIV medications (90% participants for
      Session 1; 89% for Session 2). Per exit interview responses, participants felt
      that the intervention made them think more about their health and was a motivator
      for them to take better care of their health. In conclusion, the intervention was
      feasible for YLH enrolled in the study. 

PMID- 23869651
TI  - A cobalt-based catalyst for the hydrogenation of CO2 under ambient conditions.
AB  - Because of the continually rising levels of CO2 in the atmosphere, research for
      the conversion of CO2 into fuels using carbon-neutral energy is an important and
      current topic in catalysis. Recent research on molecular catalysts has led to
      improved rates for conversion of CO2 to formate, but the catalysts are based on
      precious metals such as iridium, ruthenium and rhodium and require high
      temperatures and high pressures. Using established thermodynamic properties of
      hydricity (DeltaGH(-)) and acidity (pKa), we designed a cobalt-based catalyst
      system for the production of formate from CO2 and H2. The complex Co(dmpe)2H
      (dmpe is 1,2-bis(dimethylphosphino)ethane) catalyzes the hydrogenation of CO2,
      with a turnover frequency of 3400 h(-1) at room temperature and 1 atm of 1:1
      CO2:H2 (74,000 h(-1) at 20 atm) in tetrahydrofuran. These results highlight the
      value of fundamental thermodynamic properties in the rational design of
      catalysts.

PMID- 23869652
TI  - Assessing the cultural competence of oral health research conducted with migrant
      children.
AB  - OBJECTIVES: Traditional assessment of research quality addresses aspects of
      scientific rigor, however, ensuring barriers to participation by people of
      different cultural backgrounds are addressed requires cultural competence. The
      aim of this research was to assess the cultural competence of oral health
      research conducted with migrant children. METHODS: A protocol was developed with
      explicit inclusion and exclusion criteria. Electronic databases were searched
      from 1995 to 2009. Each study was assessed for cultural competence using the
      assessment criteria and a template developed as a proof-of-concept approach.
      RESULTS: Of the 2059 articles identified, 58 met inclusion criteria (n = 48
      studies). There were four (8.3%) cohort studies, five (10.4%) intervention
      studies, 37 (77.1%) quantitative cross-sectional studies, and two (4.2%) were
      qualitative studies. Overall, migrant children had worse oral health outcomes in
      all studies compared with their host-country counterparts. All studies rated
      poorly in the cultural competence assessment. CONCLUSIONS: Appropriate inclusion
      of all potentially vulnerable groups in research will result in better estimates
      and understandings of oral health, and more reliable recommendations for
      prevention and management.

PMID- 23869653
TI  - Mothers with an eating disorder: 'food comes before anything'.
AB  - There is little research that has presented the voices of mothers with an eating
      disorder (ED). The aim of this study was to clinicians present the experiences of
      mothers, drawn from the community, who have an ED and their perceptions regarding
      how their ED impacts on their children and parenting. Semi-structured, individual
      interviews were conducted with nine mothers with various EDs. Interpretative
      Phenomenological Analysis, alongside member checks and inter-rater reliability,
      was employed to analyze data. Six themes were identified: (1) the impact of an ED
      on children; (2) modelling disturbed eating behaviours; (3) prioritizing food
      before children's needs, or as described by one participant, 'food comes before
      anything'; (4) children motivate recovery; (5) secrecy within families; and (6)
      treatment needs. Overall, mothers juggled to balance the competing demands of an
      ED and the needs of their children. The need for clinicians to acknowledge and
      support a mother's role when treating EDs is highlighted.

PMID- 23869654
TI  - Effect of pancreatic juice cytology and/or endoscopic ultrasound-guided fine
      needle aspiration biopsy for pancreatic tumor.
AB  - BACKGROUND AND AIM: Endoscopic ultrasound-guided fine-needle aspiration biopsy
      (EUS-FNA) can now provide a cytopathological diagnosis of pancreatic malignancy
      with higher success rates. However, EUS-FNA cannot be carried out for lesions of
      minimally invasive carcinoma because they cannot be detected by endoscopic
      ultrasonography, and in cases of intraductal papillary mucinous carcinoma (IPMC)
      because of the potential for needle tract seeding. A recent study has shown that
      pancreatic juice cytology (PJC) is useful for diagnosing pancreatic cancer. This
      study's aim was to evaluate whether PJC strengthens the diagnostic power of EUS
      FNA for pancreatic masses. METHODS: A total of 161 patients, who were suspected
      to have a pancreatic mass on conventional ultrasound and/or computed tomography,
      was enrolled. RESULTS: EUS-FNA was carried out in 121 cases, and PJC was
      performed in 83 cases. An adequate specimen was obtained for EUS-FNA in 96.0% and
      for PJC in 98.9%. The sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy were 86.0%, 100%, 100%, 70.5%, and 89.5%
      for EUS-FNA, and 71.4%, 100%, 100%, 84.4%, and 88.8% for PJC, respectively. EUS
      FNA and/or PJC for the diagnosis of pancreatic tumor had a sensitivity of 92.5%,
      specificity of 100%, positive predictive value of 100%, negative predictive value
      of 91.7%, and accuracy of 95.9%. The diagnostic accuracy of EUS-FNA and/or PJC
      was significantly higher than that of EUS-FNA alone or PJC alone. CONCLUSION: PJC
      improved the diagnostic utility of EUS-FNA for pancreatic tumor.

PMID- 23869655
TI  - Effect of intravenous lipid emulsion in patients with acute glyphosate
      intoxication.
AB  - BACKGROUND: Although glyphosate intoxication has been considered minimally toxic
      in animals, severe toxicity has been observed in humans due to surfactant. We
      aimed to examine the potential therapeutic effects of intravenous lipid emulsion
      (ILE) on the patients with acute glyphosate intoxication. METHODS: This study
      enrolled 64 glyphosate-intoxicated patients with allocation to two groups: those
      treated with ILE (ILE group, n = 22), and control patients treated with only
      supportive (conservative) care. Control patients were selected by matching for
      the amount ingested and time since ingestion. Twenty-two control patients were
      separately selected from the 42 patients receiving supportive care only. In ILE
      group, 20% lipid emulsion product was injected intravenously at the rate of 20
      mL/h for the patients who ingested less than 100 ml of glyphosate. In the
      patients who ingested more than 100 ml of glyphosate, the loading dose was 500 ml
      for 2-3 h according to the status of the patients, followed by a maintenance dose
      of 1000 ml for the next 24 h. RESULTS: Thirteen patients received high dose of
      ILE because the ingestion amount was more than 100 ml. None of the ILE group
      suffered from the complication of hypotension, while approximately 41% of the
      control group developed the complication. Additionally, arrhythmia was not
      observed in the ILE group. The incidence of mental change, respiratory failure,
      and acute kidney injury was similar between the two groups. CONCLUSIONS: ILE
      administration was associated with lower incidence of hypotension and arrhythmia
      in patients with acute glyphosate intoxication. ILE administration seems to be an
      effective treatment modality in patients who ingested sufficient amount of
      glyphosate herbicide that is expected to bring about significant toxicity.

PMID- 23869656
TI  - A case series of patients with lamotrigine toxicity at one center from 2003 to
      2012.
AB  - INTRODUCTION: Lamotrigine is a phenyltriazine compound that inhibits voltage
      gated sodium channels, decreasing release of glutamate and aspartate, and
      inhibits serotonin, norepinephrine and dopamine reuptake. Reports of toxicity in
      the literature are limited to case reports and primarily involve coingestants.
      This case series is intended to report the clinical manifestations of lamotrigine
      toxicity. METHODS: This retrospective case series from 2003 to 2012 studies the
      effects of lamotrigine toxicity when not confounded by coingestants. Admission
      records at an inpatient toxicology center were reviewed for lamotrigine-only
      exposure based on history with supporting laboratory data when available. After
      identification, these charts were reviewed again to characterize vital signs,
      neurological examination findings, specific laboratory and electrocardiography
      parameters, and complications. RESULTS: Fifty-seven patients were identified with
      possible lamotrigine toxicity. Nine patients, including three toddlers, had
      lamotrigine-only ingestions. Three of these patients had seizures, four were
      hypertensive, five were tachycardic, and four experienced tachypnea. Mental
      status was altered in all nine (depressed (n = 4), agitated (n = 5) or both (n =
      3)). Five patients were hyperreflexic and experienced intermittent myoclonus, and
      two had inducible clonus. On electrocardiogram, two patients experienced QRS
      prolongation (114-116 ms), and four had QTc prolongation (463-586 ms). No patient
      had life-threatening symptoms or signs. Serum levels of lamotrigine were
      available in seven patients, and averaged 35.4 mg/L (17-90 mg/L). The therapeutic
      range for sLTG is 3-14 mg/L. CONCLUSIONS: Lamotrigine toxicity manifested with
      minor-moderate neurologic and/or electrocardiographic effects. Toxicity reflects
      the known pharmacologic actions of lamotrigine: serotonin, norepinephrine and
      dopamine reuptake inhibition, and sodium channel blockade.

PMID- 23869657
TI  - Behavioral and physiologic adverse effects in adolescent and young adult
      emergency department patients reporting use of energy drinks and caffeine.
AB  - INTRODUCTION: This pilot study assessed the prevalence of physiologic and
      behavioral adverse effects among adolescent (13-17 years) and adult (18-25 years)
      emergency department patients who reported energy drink and/or caffeinated-only
      beverage use within the 30 days prior to emergency department presentation. It
      was hypothesized that energy drink users would report more adverse effects than
      those who used only traditional caffeinated beverages such as coffee, tea, or
      soft drinks. METHODS: This cross-sectional pilot study was conducted in two urban
      emergency departments, one adult and one pediatric. Eligible patients were
      enrolled during a 6-week period between June and August 2010. Participants
      completed a tablet computer-based, self-administered, anonymous questionnaire
      about their past 30-day energy drink and/or caffeinated-only beverage use,
      substance use, and experience of 10 physiologic and 10 behavioral symptoms.
      Multivariable logistic regression and negative binomial regression models,
      adjusted for age, gender, and substance use, were created to compare the
      occurrence of each adverse effect between energy drink and caffeinated-only
      beverage users. Odds ratios (ORs) and incidence rate ratios (IRRs) were
      estimated. RESULTS: Of those enrolled, 53.3% reported consuming energy drinks,
      39.1% caffeinated-only beverages, and 7.6% no energy drinks or caffeinated-only
      beverages within the past 30 days. In multivariable logistic regression models,
      energy drink users were more likely than caffeinated-only beverage users to
      report having "gotten into trouble at home, school, or work" in the past 30 days
      (OR: 3.12 [1.24-7.88]). In the negative binomial regression multivariable models,
      more behavioral effects were reported among drug users (IRR: 1.50 [1.18-1.93]),
      and more physiologic effects were reported among tobacco users (IRR: 1.42 [1.13
      1.80]) and females (IRR: 1.48 [1.21-1.80]), but not among energy drink users.
      CONCLUSIONS: Energy drink users and substance users are more likely to report
      specific physiologic and behavioral adverse effects. Emergency department
      clinicians should consider asking patients about energy drink and traditional
      caffeine usage and substance use when assessing patient symptoms.

PMID- 23869658
TI  - A catalyst-free one-pot construction of skeletons of 5-methoxyseselin and
      alloxanthoxyletin in water.
AB  - In refluxing water and without an additional catalyst, electron-rich phenols
      could react with alkynoic acids or alkynoates to provide coumarin structures. The
      skeletons of two natural pyranocoumarins, 5-methoxyseselin and alloxanthoxyletin,
      could be constructed (total yield up to 76%) in an aqueous multicomponent
      reaction in which isoprenyl acetate, propiolic acid, and phloroglucinol were
      simply mixed and refluxed in water. 

PMID- 23869660
TI  - Challenges of proper placebo control for non-invasive brain stimulation in
      clinical and experimental applications.
AB  - A range of techniques are now available for modulating the activity of the brain
      in healthy people and people with neurological conditions. These techniques,
      including transcranial magnetic stimulation (TMS) and transcranial current
      stimulation (tCS, which includes direct and alternating current), create magnetic
      or electrical fields that cross the intact skull and affect neural processing in
      brain areas near to the scalp location where the stimulation is delivered. TMS
      and tCS have proved to be valuable tools in behavioural neuroscience
      laboratories, where causal involvement of specific brain areas in specific tasks
      can be shown. In clinical neuroscience, the techniques offer the promise of
      correcting abnormal activity, such as when a stroke leaves a brain area
      underactive. As the use of brain stimulation becomes more commonplace in
      laboratories and clinics, we discuss the safety and ethical issues inherent in
      using the techniques with human participants, and we suggest how to balance
      scientific integrity with the safety of the participant. 

PMID- 23869659
TI  - Comparative assessment of PDE 4 and 7 inhibitors as therapeutic agents in
      experimental autoimmune encephalomyelitis.
AB  - BACKGROUND AND PURPOSE: PDE4 inhibition suppresses experimental autoimmune
      encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However,
      side effects hinder PDE4 inhibitors clinical use. PDE7 inhibition might
      constitute an alternative therapeutic strategy, but few data about the anti
      inflammatory potential of PDE7 inhibitors are currently available. We have used
      the EAE model to perform a comparative evaluation of PDE4 and PDE7 inhibition as
      strategies for MS treatment. EXPERIMENTAL APPROACH: Two PDE7 inhibitors, the
      sulfonamide derivative BRL50481 and the recently described quinazoline compound
      TC3.6, were assayed to modulate EAE in SJL mice, in comparison with the well
      known PDE4 inhibitor Rolipram. We evaluated clinical signs, presence of
      inflammatory infiltrates in CNS and anti-inflammatory markers. We also analysed
      the effect of these inhibitors on the inflammatory profile of spleen cells in
      vitro. KEY RESULTS: TC3.6 prevented EAE with efficacy similar to Rolipram, while
      BRL50481 had no effect on the disease. Differences between both PDE7 inhibitors
      are discussed. Data from Rolipram and TC3.6 showed that PDE4 and PDE7 inhibition
      work through both common and distinct pathways. Rolipram administration caused an
      increase in IL-10 and IL-27 expression which was not found after TC3.6 treatment.
      On the other hand, both inhibitors reduced IL-17 levels, prevented infiltration
      in CNS and increased the expression of the T regulator cell marker Foxp3.
      CONCLUSIONS AND IMPLICATIONS: These results provide new information about the
      effects of Rolipram on EAE, underline PDE7 inhibition as a new therapeutic target
      for inflammatory diseases and show the value of TC3.6 to prevent EAE, with
      possible consequences for new therapeutic tools in MS.

PMID- 23869661
TI  - Screening for HIV-related neurocognitive impairment in clinical practice:
      challenges and opportunities.
AB  - With increasingly successful management of HIV, focus has shifted away from AIDS
      related complications to other chronic co-morbidities. For HIV-related cognitive
      problems, the true aetiopathogenesis and epidemiology remains unclear. Rather
      than a systematic review, this paper presents the challenges and the
      opportunities we faced in establishing our own clinical service. Papers were
      identified using Pubmed and the terms "screening", "HIV" and "neurocognitive".
      This article covers the background of HIV-associated neurocognitive disorders
      (HAND) with a focus on HIV-related neurocognitive impairment (NCI), detailing
      classification, prevalence, diagnostic categories and diagnostic uncertainties.
      Screening is discussed, including a comparison of the available screening tools
      for cognitive deficits in HIV-infected patients and the importance of practice
      effects. Discussed also are the normal ranges and the lack thereof and potential
      investigations for those found to have impairments. We conclude by discussing the
      role of NCI screening in routine clinical care at the current time. 

PMID- 23869662
TI  - NisC binds the FxLx motif of the nisin leader peptide.
AB  - Nisin is a model system for lantibiotics, a class of peptides displaying
      antimicrobial activity against various Gram-positive bacteria. After ribosomal
      synthesis, the precursor peptide is modified in two steps, of which the last one
      involves consecutive cyclization reactions mediated by the cyclase NisC. Here, we
      present a detailed in vitro study of the interaction between NisC and the nisin
      precursor peptide. Our results unravel a specific interaction of NisC with the
      leader peptide independent of the maturation state. Furthermore, mutagenesis
      studies identified a specific binding sequence within the leader. Two amino acids
      (F-18 and L-16) within the highly conserved -FNLD- box of class I lantibiotics
      are essential for binding. They represent a potential general binding motif
      between leader peptides of a group of lantibiotics with their cyclase family. In
      summary, these in vitro data provide a new perception on the complexity of the
      lantibiotic modification machineries. 

PMID- 23869663
TI  - Effects of errors and gaps in spatial data sets on assessment of conservation
      progress.
AB  - Data on the location and extent of protected areas, ecosystems, and species'
      distributions are essential for determining gaps in biodiversity protection and
      identifying future conservation priorities. However, these data sets always come
      with errors in the maps and associated metadata. Errors are often overlooked in
      conservation studies, despite their potential negative effects on the reported
      extent of protection of species and ecosystems. We used 3 case studies to
      illustrate the implications of 3 sources of errors in reporting progress toward
      conservation objectives: protected areas with unknown boundaries that are
      replaced by buffered centroids, propagation of multiple errors in spatial data,
      and incomplete protected-area data sets. As of 2010, the frequency of protected
      areas with unknown boundaries in the World Database on Protected Areas (WDPA)
      caused the estimated extent of protection of 37.1% of the terrestrial Neotropical
      mammals to be overestimated by an average 402.8% and of 62.6% of species to be
      underestimated by an average 10.9%. Estimated level of protection of the world's
      coral reefs was 25% higher when using recent finer-resolution data on coral reefs
      as opposed to globally available coarse-resolution data. Accounting for
      additional data sets not yet incorporated into WDPA contributed up to 6.7% of
      additional protection to marine ecosystems in the Philippines. We suggest ways
      for data providers to reduce the errors in spatial and ancillary data and ways
      for data users to mitigate the effects of these errors on biodiversity
      assessments.

PMID- 23869665
TI  - Obtaining high localized spin magnetic moments by fluorination of reduced
      graphene oxide.
AB  - Fluorination was confirmed to be the most effective route to introduce localized
      spins in graphene. However, adatoms clustering in perfect graphene lead to a low
      efficiency. In this study, we report experimental evidence of the generation of
      localized spin magnetic moments on defective graphene (reduced graphene oxide)
      through fluorination. More interstingly, the result shows that defects help
      increase the efficiency of the fluorination with regard to the density of
      magnetic moments created. Fluorinated reduced graphene oxide can have a high
      magnetic moment of 3.187 * 10(-3) MUB per carbon atom and a high efficiency of
      8.68 * 10(-3) MUB per F atom. It may be attributed to the many vacancies, which
      hinder the clustering of F atoms, and introduce many magnetic edge adatoms. 

PMID- 23869667
TI  - Venous thromboembolism in pregnancy and the puerperal period: a study of 1210
      events.
AB  - OBJECTIVE: The aim of this study was to describe venous thromboembolism (VTE) in
      pregnancy and the puerperal period, and to validate diagnoses of VTE. DESIGN:
      Historical cohort study. POPULATION: All pregnancies in Denmark from 1995 to
      2009. METHODS: VTE diagnoses were retrieved from national registries. MAIN
      OUTCOME MEASURES: Positive predictive value of a VTE diagnoses diagnosed during
      pregnancy or the puerperal period. Location of VTE. Incidence rate of confirmed,
      validated diagnoses of VTE and on all retrieved diagnoses of VTE. RESULTS: In 1
      297 037 pregnancies, 1436 women had a first-ever VTE diagnosis. Hospital records
      were retrieved for 1210 women (84.3%). Almost all women had relevant clinical
      symptoms and in 796 (65.8%), the diagnosis were confirmed by a positive
      diagnostic test or by instituted anticoagulation treatment. In all, 72.6, 53.7,
      58.5 and 79.1% of the diagnoses were confirmed in the first, second, third
      trimester and the puerperal period, respectively. The 796 cases of VTE included
      624 women with deep venous thrombosis only and 133 with pulmonary embolisms. Deep
      venous thrombosis was located in the left lower limb in 83.8% in pregnancy,
      compared with 67.9% in the puerperal period. CONCLUSIONS: The vast majority of
      women with a registered diagnosis of VTE had relevant symptoms. Diagnoses of VTE
      were confirmed in the medical records in two of three women. VTE diagnoses were
      most often confirmed when made in the first trimester and in the puerperal
      period. Left-sided deep venous thrombosis was the predominant type of VTE in
      pregnancy and the puerperal period.

PMID- 23869668
TI  - Triarylphosphine ligands with pendant electron-rich "[Fe(kappa2-dppe)(eta5
      C5Me5)(C=C)]-" substituents.
AB  - The synthesis of four triaylphosphine ligands featuring electron-rich Fe(II)
      "Fe(kappa(2)-dppe)(eta(5)-C5Me5)C=C-" pendant substituents in para and meta
      position(s) (1-4) is reported along with that of their corresponding radical
      cations (1-2[PF6] or 3-4[PF6]3). These triarylphosphines possessing redox-active
      organometallic substituents constitute a new class of phosphorus-based metallo
      ligands. In contrast to many related ferrocenylphosphines, these metallo-ligands
      are stable and isolable in two redox-states. Their steric and electronic
      properties are also briefly discussed. 

PMID- 23869666
TI  - TIME FOR COFFEE is an essential component in the maintenance of metabolic
      homeostasis in Arabidopsis thaliana.
AB  - Plants often respond to environmental changes by reprogramming metabolic and
      stress-associated pathways. Homeostatic integration of signaling is a central
      requirement for ensuring metabolic stability in living organisms. Under diurnal
      conditions, properly timed rhythmic metabolism provides fitness benefits to
      plants. TIME FOR COFFEE (TIC) is a circadian regulator known to be involved in
      clock resetting at dawn. Here we explored the mechanism of influence of TIC in
      plant growth and development, as initiated by a microarray analysis. This global
      profiling showed that a loss of TIC function causes a major reprogramming of gene
      expression that predicts numerous developmental, metabolic, and stress-related
      phenotypes. This led us to demonstrate that this mutant exhibits late flowering,
      a plastochron defect, and diverse anatomical phenotypes. We further observed a
      starch-excess phenotype and altered soluble carbohydrate levels. tic exhibited
      hypersensitivity to oxidative stress and abscisic acid, and this was associated
      with a striking resistance to drought. These phenotypes were connected to an
      increase in total glutathione levels that correlated with a readjustment of amino
      acids and polyamine pools. By comparatively analyzing our transcriptomic and
      metabolomic data, we concluded that TIC is a central element in plant homeostasis
      that integrates and coordinates developmental, metabolic, and environmental
      signals. 

PMID- 23869669
TI  - Results of treatment for pT1/pT2 carcinomas of the floor of mouth.
AB  - CONCLUSION: In pT2 floor of mouth cancer (FOMC), a standardized neck dissection
      (ND) should be carried out, due to the high risk of occult metastases. In cases
      of pT1 carcinomas with a clinically negative neck using high imaging standards
      and expertise a tight 'wait and watch' strategy can be used. OBJECTIVE: To report
      on the oncologic results with primary surgical treatment of pT1/pT2 FOMC and to
      examine the benefit of elective ND in cN0. METHODS: This was a retrospective
      study design including 216 patients who were treated between 1980 and 2010 for
      pT1/2 FOMC. The 5-year disease-specific survival (DSS), local and (loco)regional
      control based on the T and N classification and depth of infiltration were
      investigated. RESULTS: DSS was 79.5% and (loco)regional control was 89.8%. DSS in
      patients staged pN0 was significantly higher, at 84.6%, than in those staged pN+,
      at 60%. ND was performed in 165 patients, and adjuvant therapy was administered
      in 124 patients. Ninety patients (41.7%) were staged cN0, and 53.3% of them
      underwent elective ND. The risk of occult metastases was 4.8% in pT1 and 28.6% in
      pT2. A depth of infiltration of >= 5 mm showed a markedly higher relative
      frequency of occult neck metastases and pN+ status.

PMID- 23869670
TI  - Conservation surgery for hypopharyngeal cancer: changing paradigm from open to
      endoscopic.
AB  - CONCLUSIONS: Endoscopic laser microsurgery (ELM) provides comparable oncological
      outcomes, and improved functional recovery and laryngeal preservation compared
      with open partial laryngopharyngectomy (OPLP) in patients with early squamous
      cell carcinoma of the hypopharynx (HPSCC). The use of open surgery is declining.
      The outcome of the study provides evidence-based recommendations for surgical
      choices in HPSCC treatment. However, it is not conclusive without a larger
      prospective study. OBJECTIVES: To compare the functional and oncological results
      of ELM and OPLP in HPSCC and examine surgical trends. METHODS: From 1990 to 2008,
      53 HPSCC patients undergoing ELM (n = 25) and OPLP (n = 28) were included.
      Functional recovery, oncological results, and laryngeal preservation rate were
      analyzed. RESULTS: Patients who underwent ELM demonstrated a shorter
      decannulation period (7 vs 11 days, p = 0.010), time using a nasogastric tube (7
      vs 16 days, p = 0.043), and hospitalization stay (12 vs 22 days, p = 0.0061) than
      those who underwent OPLP. The 3-year overall and disease-specific survival rates
      were comparable between ELM and OPLP (79% vs 64%, p = 0.151, and 83% vs 71%, p =
      0.320, respectively). The ELM patients had better laryngeal preservation (92% vs
      71%, p = 0.048). The number of OPLPs performed has decreased since 2000 (68%
      before vs 32% after, p < 0.0001).

PMID- 23869664
TI  - Temporal changes and regional differences in treatment uptake of hepatitis C
      therapy in EuroSIDA.
AB  - OBJECTIVES: All HIV/hepatitis C virus (HCV)-coinfected patients with chronic HCV
      infection and >= F2 fibrosis should be considered for HCV therapy. This study
      aimed to determine the rate of HCV treatment uptake among coinfected patients in
      Europe. METHODS: EuroSIDA patients with viraemic HCV infection were included in
      the study. Poisson regression was used to identify temporal changes and regional
      differences in HCV treatment uptake. RESULTS: A total of 1984 patients were
      included in the study, with a median follow-up time of 168 months [interquartile
      range (IQR) 121-204 months]. To date, 501 (25.3%) HIV/HCV-coinfected patients
      have received HCV therapy. Treatment incidence rose from 0.33 [95% confidence
      interval (CI) 0.16-0.50] per 100 person-years of follow-up (PYFU) in 1998 to 5.93
      (95% CI 4.49-7.38) in 2007, falling to 3.78 (95% CI 2.50-5.07) in 2009. After
      adjustment, CD4 cell count > 350 cells/MUL [incidence rate ratio (IRR) 1.33 (95%
      CI 1.06-1.67) vs. CD4 count 200-350 cells/MUL] and >=F2 liver fibrosis [IRR 1.60
      (95% CI 1.14-2.25; P = 0.0065) vs. < F2 fibrosis] were predictors of anti-HCV
      treatment initiation. However, 22% of patients who remain untreated for HCV, with
      fibrosis data available, had >=F2 fibrosis and should have been considered for
      treatment, while only 36% of treated patients had >=F2 fibrosis. CONCLUSIONS:
      Although treatment incidence for HCV has increased, there remain a large
      proportion of patients indicated for treatment who have yet to be treated.

PMID- 23869671
TI  - Back to the future: transitions, technology and tao.

PMID- 23869672
TI  - Paediatric epistaxis: diagnosis and management.

PMID- 23869673
TI  - Allied health in-reach in the emergency department: does it reduce length of
      stay?

PMID- 23869674
TI  - The place of newer oral anticoagulants in the treatment of patients with non
      valvular atrial fibrillation and coronary artery disease.
AB  - With the arrival of the newer oral anticoagulants (NOACs), we now have a more
      convenient means of providing anticoagulation for patients with non-valvular
      atrial fibrillation (AF). Are there any particular considerations for the many
      patients who also have coronary artery disease? For many patients there is an
      obvious need to use the newer agents but for others, such as those who simply
      refuse to consider using a vitamin K antagonist (VKA) such as warfarin, the
      decision may be more problematical. 

PMID- 23869675
TI  - Ultrasound-guided subclavian venous catheterisation - is this the way forward? A
      narrative review.
AB  - Central venous catheterisation is a commonly performed procedure in anaesthesia,
      critical care, acute and emergency medicine. Traditionally, subclavian venous
      catheterisation has been performed using the landmark technique and because of
      the complications associated with this technique, it is not commonly performed in
      the United Kingdom - where the accepted practice is ultrasound-guided internal
      jugular vein catheterisation. Subclavian vein catheterisation offers particular
      advantages over the internal jugular and femoral vein sites such as reduced rates
      of line-related sepsis, improved patient comfort and swifter access in trauma
      situations where the internal jugular vein may not be easily accessible. There is
      a growing body of evidence to suggest a potential emerging role for ultrasound
      guided subclavian vein catheterisation. Barriers to this approach include many
      physicians still believing that the clavicle obscures imaging of the vein. In
      this article, we review the evidence supporting ultrasound-guided subclavian vein
      catheterisation and ask the question whether, in view of it potential advantages,
      it could be the way forward? 

PMID- 23869676
TI  - Lower incidence of inappropriate shock therapy in patients with combined cardiac
      resynchronisation therapy defibrillators (CRT-D) compared with patients with non
      CRT defibrillators (ICDs).
AB  - INTRODUCTION: A significant number of patients experience inappropriate shock
      therapy (IST) from implantable cardioverter-defibrillators (ICD). An increasing
      number of patients with advanced heart failure receive combined ICD and cardiac
      resynchronisation therapy devices (CRT-D). The incidence of IST in this group is
      less well described. We aimed to assess the incidence and predictors of IST in
      CRT-D patients. METHODS: A retrospective cohort study of prospectively collected
      data on patients who received an ICD and CRT-D between October 2007 and January
      2009 at our institution were studied. The primary outcome measures were the IST
      event rate and all-cause mortality. RESULTS: A total of 185 patients with ICD/CRT
      D (100/85) were included in the analysis. Eighteen patients experienced 35
      episodes of IST during the follow-up (21 +/- 13 months). There was a
      significantly lower IST cumulative event rate in the CRT-D vs. ICD group, 5% (CI:
      1-13%) vs. 19% (95% CI: 11-30%) by 24 months, (p = 0.017). The majority of the
      IST was caused by atrial arrhythmias with atrial fibrillation accounting for 28
      episodes of IST in nine patients. Multivariate analysis using Cox hazard model
      including baseline characteristics and coexisting appropriate shock therapy
      showed that a history of atrial fibrillation/flutter was the strongest
      independent predictor of IST with a hazard ratio of 3.53 (p = 0.019). CONCLUSION:
      Patients with CRT-D had a significantly lower incidence of IST compared with
      patients receiving an ICD. Given that atrial arrhythmia remained the commonest
      trigger for IST, our finding lends support to the hypothesis that CRT may reduce
      atrial fibrillation burden in patients receiving CRT-D.

PMID- 23869677
TI  - Resource utilisation and quality of life following initiation of insulin detemir
      in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: Barriers to insulin initiation in type 2 diabetes mellitus (T2DM)
      include fear of treatment complexity and perceived lack of time and resources by
      primary care physicians. The SOLVE study investigated the effect of insulin
      initiation on resource utilisation and patient quality of life. METHODS: SOLVE
      was a 24-week cohort study in 10 countries evaluating the safety and
      effectiveness of initiating once-daily insulin detemir in patients with T2DM.
      Patient quality of life was assessed using the Insulin Treatment Appraisal Scale
      (ITAS). RESULTS: A total of 14,611 (84%) patients completed the 24-week study.
      During the study, HbA1c improved by 1.3 +/- 1.5%. The corresponding insulin dose
      increased from 13 +/- 6 IU (0.16 +/- 0.09 IU/kg) at baseline, to 22 +/- 16 IU
      (0.27 +/- 0.17 IU/kg) at final visit. FlexPen was the preferred device (63%) for
      insulin administration. The time taken to teach patients to self-inject and
      perform dose self-adjustment was 15 +/- 13 min and 11 +/- 11 min, respectively.
      The quality of life analysis included 6875 patients. The addition of insulin was
      associated with an improvement in mean ITAS score [-3.5 (95% CI -3.8, -3.3), p <
      0.001]. Physicians reported the use or self-adjustment of insulin detemir as easy
      or very easy in 79% of participants; and satisfaction with the level of glycaemic
      control was reported for 74% of patients. CONCLUSIONS: Initiating basal insulin
      therapy resulted in a substantial decrease in HbA1c and improved patients'
      perceptions of insulin treatment.

PMID- 23869678
TI  - PDE5 inhibitors: considerations for preference and long-term adherence.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent condition affecting
      nearly one in five men worldwide. The advent of phosphodiesterase type 5
      inhibitors (PDE5i) has revolutionised the ED treatment landscape and provided
      effective, minimally invasive therapies to restore male sexual function.
      MATERIALS AND METHODS: A pubmed search was performed of all English language
      articles from 1996 to present reviewing PDE5i, including pharmacokinetics,
      efficacy profiles and comparisons, where available. RESULTS: Currently available
      PDE5i in the United States include sildenafil, vardenafil, tadalafil and
      avanafil, each of which has unique side effect, pharmacokinetic and outcome
      profiles. Sildenafil is associated with increased rate of visual changes,
      vardenafil with QT prolongation and tadalafil with lower back pain. Avanafil and
      vardenafil orodispersible tablet rapidly achieve peak plasma concentration, which
      results in faster onset of action, whereas tadalafil exhibits the longest half
      life. First time response to PDE5i is approximately 60-70%, with no significant
      differences in efficacy noted among therapies. The literature does not clearly
      demonstrate a preference for one drug. High-treatment success rates (89%) were
      reported when patients were prescribed all available PDE5i. Daily dosing with
      tadalafil is associated with improved erectile function (EF) over time. Finally,
      novel modes of patient-provider interaction, including internet-based education,
      communication and prescribing, may also improve long-term adherence. CONCLUSIONS:
      PDE5i represent first line therapy for ED with excellent overall efficacy and
      satisfactory side effect profiles. Enhanced communciation, coupled with increased
      knowledge of drug characteristics, comparative treatment regimens and optimal
      prescribing patterns, offer compelling tools to improve long-term treatment
      success.

PMID- 23869679
TI  - Understanding the course of Peyronie's disease.
AB  - AIMS: To correct common misconceptions about Peyronie's disease (PD) that present
      obstacles to early recognition and treatment. METHODS: The prevalence, natural
      disease course, psychosocial effects and treatment considerations for patients
      with PD were reviewed. RESULTS: Studies over the past decade have shown that the
      prevalence of PD may be higher (up to 20%) than previously thought. PD can lead
      to emotional and relationship distress. Nearly 10% of men who present with PD are
      younger than 40. Both younger age and comorbid vascular disease have been
      associated with more severe and progressive PD. In the majority of patients,
      symptoms will either deteriorate or remain stable. PD is often associated with
      erectile dysfunction (ED). Effective, minimally invasive treatments used early in
      the disease course include unapproved and/or investigational intralesional
      injection therapy with verapamil, interferon (IFN) alpha-2b, or collagenase
      clostridium histolyticum (CCH). Surgical intervention is considered in patients
      with ED and/or penile deformity that impairs sexual functioning; however,
      preoperative discussion of appropriate expectations is important. DISCUSSION: The
      availability of effective minimally invasive and surgical therapies for PD
      suggests that active management should be considered over a 'wait-and-see'
      approach. CONCLUSION: Providing early intervention and improved
      education/awareness of PD as a chronic and progressive disorder may result in
      improved physical and psychosocial outcomes for PD patients. As general
      practitioners are often the first contact for men with PD, they are well
      positioned to recognise symptoms early and promptly refer patients for further
      evaluation and treatment.

PMID- 23869680
TI  - The association between the self-perception period of overactive bladder symptoms
      and overactive bladder symptom scores in a non-treated population and related
      sociodemographic and lifestyle factors.
AB  - AIMS: To investigate the association between the self-perception period of OAB
      symptoms (SP-OAB) and the overactive bladder symptom score (OABSS), along with
      related sociodemographic and lifestyle factors. METHODS: This was a cross
      sectional study comprised of 192 men aged 40 years and older who participated in
      a prostate examination survey between February and May 2009 and proved to have
      OAB. Survey questionnaires included items on the OABSS and the SP-OAB assessed by
      the OABSS. Various sociodemographic and lifestyle factors were also included.
      RESULTS: The average SP-OAB period was 24.72 +/- 45.75 months and became
      significantly longer as the severity of OAB increased in correlation analysis
      (coefficient = 0.501, p < 0.001). Age, education, income, regular check-up,
      health maintenance and occupation were all risk factors in both OABSS and SP-OAB
      in univariate analysis. Body mass index (BMI), family size and SP-OAB were risk
      factors for OABSS in univariate analysis. Age and regular check-ups were factors
      in both OABSS and SP-OAB in multivariate analysis. BMI, income and SP-OAB were
      risk factors for OABSS. CONCLUSION: These findings suggest that the SP-OAB is an
      independent risk factor for OAB progression and that various sociodemographic and
      lifestyle factors affect OABSS. The self-perception period should be considered
      in the treatment and prevention of OAB symptoms.

PMID- 23869681
TI  - Complementary therapies in hemifacial spasm and comparison with other movement
      disorders.
AB  - OBJECTIVES: We determined the prevalence, range and factors influencing the use
      of complementary therapy among hemifacial spasm patients and compared the
      patterns of use of complementary therapies across different movement disorders in
      a systematic pooled analysis of published literature. METHODS: A structured
      questionnaire was administered to 96 hemifacial spasm patients evaluating
      frequency of complementary therapy use, and factors influencing patients'
      decision to seek these therapies. We also performed a PubMed search of
      epidemiology studies on use of complementary therapies in movement disorders.
      RESULTS: Fifty-one per cent of patients had tried complementary therapies, of
      which 47% reported some perceived benefit and 4.1% informed their doctor.
      Acupuncture (71.4%) and facial massage (17.6%) were most commonly used.
      Complementary therapy use was associated with greater HFS severity. The mean cost
      of treatment was about $78 per month. We identified eight articles on use of
      complementary therapies in movement disorders; Parkinson's disease (5), Tourette
      syndrome (2) and dystonia (1). Twenty-five to 88% of patient had tried
      complementary therapies, of which 32-70% reported some benefit. Trials of
      acupuncture (2-63%) and massage (7-38%) were reported across the spectrum of
      movement disorders studied. Mean cost of complementary therapies varied from 43
      to 102 USD per month. CONCLUSION: Complementary therapies are used by over 50% of
      HFS patients, and the use is correlated with severity of disease. Despite
      differences in race, culture and population demographics, acupuncture and massage
      are used by patients across the spectrum of movement disorders.

PMID- 23869682
TI  - Front-loading allied health intervention in the emergency department does not
      reduce length of stay for admitted older patients.
AB  - AIMS: Allied health intervention may play an important role in the timely
      discharge of older people admitted to hospital. The impact of early allied health
      intervention on length of stay has not been quantified. We sought to determine
      whether early allied health intervention conducted in the emergency department
      (ED) reduces hospital length of stay in older patients admitted with common
      diagnoses. METHODS: A non-randomised prospective pragmatic study in ED patients
      aged 65 and over diagnosed with one or more of six conditions (cerebrovascular
      insufficiency; fractured neck of femur; cardiac failure; myocardial ischaemia;
      exacerbation of chronic airways disease; respiratory tract infection).
      Intervention patients receiving comprehensive allied health
      assessment/intervention by at least one professional working in a care
      coordination team were compared with patients who underwent no assessment. The
      primary outcome measure was hospital length of stay measured in hours from
      commencement of inpatient bed occupancy to discharge or death. A zero truncated
      negative binomial regression model was used to analyse length of stay while
      adjusting for covariates. RESULTS: In 2121 patients and 1451 comparators, there
      was no difference in length of stay (median 88 vs 87 h) on unadjusted (log-rank p
      0.28) or adjusted (IRR 0.97, p 0.32) analysis. CONCLUSIONS: Front loading allied
      health assessment in ED has no effect on hospital length of stay.

PMID- 23869683
TI  - How does cognitive impairment impact on functional improvement following the
      rehabilitation of elderly patients?
AB  - AIMS: It has been suggested that patients with cognitive impairment do not
      benefit from rehabilitation or that rehabilitation gains are reduced. Most
      studies focus on absolute gain rather than gains in individual functional areas.
      The Barthel activities of daily living (ADL) score is a tool, which is used
      widely and comprises 10 functional domains. This study aimed to assess the
      response to rehabilitation based on improvement or deterioration on the Barthel
      ADL score for patients with different cognitive abilities METHODS: This
      independence measure was assessed at specific time periods in an observational
      study of 241 patients undergoing in-patient rehabilitation. Therapy was delivered
      formally by physiotherapists and occupational therapists and also informally by
      nursing staff. Patients were divided into four groups according to cognition.
      Group 1 (MMSE, mini-mental state examination 27-30), normal cognition, Group 2
      (MMSE 21-26) mild impairment, Group 3 (MMSE 11-20) moderate impairmentand Group 4
      (MMSE 0-10) severe impairment. RESULTS: Statistically significant improvement was
      made in most of the functional domains by patients with normal cognition and mild
      cognitive impairment (p < 0.0025). The exception to this for both groups was in
      the areas of feeding and bowels because of the fact that most patients were
      independent with these aspects on admission. Group 3 patients made improvements
      in the domains of grooming, dressing, toileting, transferring and mobility. Group
      4 patients did not demonstrate statistically significant improvement in any
      domain although there were trends for improvement in mobility and transferring.
      CONCLUSIONS: This study demonstrated that cognitive impairment did have an impact
      on the ADL that patients improved in following rehabilitation. However, even
      patients with moderate cognitive impairment made significant gains with many ADL.

PMID- 23869685
TI  - Core temperature and heart rate response to repeated bouts of firefighting
      activities.
AB  - During live-fire firefighting operations and training evolutions, firefighters
      often consume multiple cylinders of air and continue to wear their personal
      protective equipment even after fire suppression activities have ceased. However,
      most studies have only reported core temperature changes during short-term
      firefighting activities and have shown a very modest increase in core
      temperature. Therefore, the purpose of this study is to evaluate core temperature
      and heart rate (HR) during repeated bouts of firefighting activity over ~3 h. The
      results of this study show that core temperatures increase by an average of 1.9
      degrees C--to a larger magnitude than previously reported--and continue to
      increase during subsequent work cycles (38.4 vs. 38.7) even after long breaks of
      more than 30 min. The rate of core temperature increase during work continues to
      increase later in the training exercise (from 0.036 to 0.048 degrees C/min),
      increasing the risk for exertional heat stress particularly if long-duration
      firefighting activity is required at these later times. PRACTITIONER SUMMARY: To
      date, core temperature and HR changes during firefighting have been reported for
      short-term studies, which may significantly underestimate the physiological
      burden of typical firefighting activities. Firefighter core temperatures are
      shown to increase to a larger magnitude than previously observed and the rate of
      rise in core temperature increases during subsequent firefighting activities.

PMID- 23869684
TI  - The different roles of neighbourhood and individual social capital on oral health
      related quality of life during pregnancy and postpartum: a multilevel analysis.
AB  - OBJECTIVE: Social capital incorporates neighbourhood and individual levels of
      interactions and influences health. The objective of this was to assess the
      association of neighbourhood and individual social capital with oral health
      related quality of life (OHRQoL) in pregnant and postpartum women. METHODS: This
      was a follow-up prevalence multilevel study on a representative sample of 1248
      women grouped into 55 neighbourhoods. OHRQoL was assessed in the postpartum
      period using the Oral Health Impact Profile questionnaire (OHIP-14). Exploratory
      variables were gathered during the first trimester of pregnancy and included
      neighbourhood social capital (neighbourhood-level measure), individual social
      capital (social support and social networks), demographic and socio-economic
      variables, oral health measures, and health-related behaviours. RESULTS: The
      multilevel ordered multinomial logistic regression showed that neighbourhood
      social capital did not significantly affect women's OHRQoL during pregnancy and
      postpartum period. Individual social capital measures were independently
      associated with high OHRQoL. Lack of family social network increased the odds for
      high OHRQoL (OR = 1.44, 95% CI: 1.08-1.92). Individuals with high levels of
      positive social interaction were less likely to report high scores of OHRQoL (OR
      = 0.90, 95% CI: 0.82-0.98). CONCLUSION: Individual social capital was of greater
      relevance to women's OHRQoL in and after pregnancy than neighbourhood social
      capital. These findings suggest that quality of personal and social resources of
      pregnant women are more important for OHRQoL than the neighbourhoods where the
      women live.

PMID- 23869686
TI  - Migraine with aura and silent brain infarcts lack of mediation of patent foramen
      ovale.
AB  - BACKGROUND AND PURPOSE: Population-based studies have shown a heightened
      prevalence of clinically silent brain infarcts in subjects who have migraine with
      aura (MA). We sought to determine whether this association could be confirmed in
      young patients with cryptogenic ischemic stroke, and explored the role of patent
      foramen ovale (PFO) as a potential underlying mechanism. METHODS: Patients were
      selected from a registry of young patients consecutively treated for ischemic
      stroke in a tertiary university hospital among those without definite cause of
      stroke. Patients with PFO were matched for age and gender with patients with
      normal atrial septum. Migraine and MA were evaluated after patient selection and
      matching. Silent brain infarcts were independently evaluated on MRI. RESULTS: We
      included 100 patients [60 men; mean age (SD), 44.8 years (8.3)], 50 patients with
      PFO. We found silent brain infarcts in 36 patients and MA in 13 patients. MA was
      more frequent in patients with silent brain infarcts than in patients without
      silent brain infarcts (25.0% vs. 6.3%; OR, 5; 95% CI, 1.4-17.6; P = 0.01).
      Traditional cardiovascular risk factors were not associated with silent brain
      infarcts. PFO was neither associated with MA (OR, 1.7; 95% CI, 0.5-5.3) nor
      silent brain infarcts (OR, 0.7; 95% CI, 0.3-1.5). The association of MA with
      silent brain infarcts was not altered after adjustment for PFO. CONCLUSION:
      Findings suggest that silent brain infarcts in young patients with cryptogenic
      stroke is associated with MA. We found no evidence for a mediating effect of PFO
      on this association.

PMID- 23869688
TI  - The acute, genetic, developmental and inhalation toxicology of trans-1
      chloro,3,3,3-trifluoropropene (HCFO-1233zd(E)).
AB  - Trans-1-chloro,3,3,3-trifluoropropene (HCFO-1233zd(E)) is being developed as a
      foam blowing agent, refrigerant and solvent because it has a very low global
      warming potential (<10), as contrasted to the hydrofluorocarbons (>500). The
      toxicology profile is described. The acute 4-hour 50% lethal concentration value
      in rats receiving HCFO-1233zd(E) was 120 000 ppm. The no observed effect level
      (NOEL) in cardiac sensitization studies in dogs was 25 000 ppm. In a 2-week range
      finding study, rats were exposed to HCFO-1233zd(E) at levels of 0, 2000, 7500 and
      20 000 ppm 6 hours/day for 5 days/week. Histopathological changes in the heart
      described as multifocal mononuclear infiltrates were observed in males (mid- and
      high-exposure group) and females (high-exposure group), suggesting this organ was
      the target for HCFO-1233zd(E) toxicity. In a 4-week study, rats were exposed to
      0, 2000, 4500, 7500 and 10 000 ppm. The only finding was an increase in potassium
      (mid- and high-exposure males). No increase was observed after a 2-week recovery
      period, nor in a subsequent 13-week toxicity study. In a 13-week study, rats were
      exposed to 4000, 10 000 and 15 000 ppm 6 hours/day for 5 days/week. Findings
      consisted of multifocal mononuclear cell infiltrates in the heart with a
      NOEL/lowest observed adverse effect level of 4000 ppm. No genetic toxicity was
      observed in a battery of genetic toxicity studies. In a rat prenatal
      developmental toxicity study, dilated bladders were observed in the high-exposure
      group fetuses (15 000 ppm), a finding of unclear significance. HCFO-1233zd(E) was
      not a developmental toxin in rabbits, even at exposure levels up to 15 000 ppm.

PMID- 23869689
TI  - Radiotherapy for patients with unresectable advanced hepatocellular carcinoma
      with invasion to intrahepatic large vessels: efficacy and outcomes.
AB  - BACKGROUND AND AIM: To examine the efficacy and outcomes of radiotherapy (RT) in
      patients who have hepatocellular carcinoma with invasion to intrahepatic large
      vessels (IHLVs). METHODS: Sixty-seven patients who had advanced hepatocellular
      carcinoma with invasion to IHLVs received three-dimensional conformal RT. IHLV
      invasion was associated with portal venous tumor thrombosis in 40 patients, tumor
      thrombosis involving the hepatic vein in 17, and both findings in 10. A daily
      radiation dose of 1.8-2 Gy was administered using 6 or 10 MV X-rays to deliver a
      total dose of 30-56 Gy. RESULTS: The overall objective response rate (complete
      response plus partial response) was 45% (n = 30). The median survival time was
      13.7 months in the responder group and 5.9 months in the nonresponder group. An
      objective response was observed in 28 (56%) of 50 patients with Child-Pugh (C-P)
      class A and in 2 (12%) of 17 patients with C-P class B. Hepatic function of C-P
      class A was an independent factor for both RT responder and overall survival on
      Cox regression analysis (hazard ratio = 9.5, 95% confidence interval = 1.97-46.2,
      P = 0.005; and hazard ratio = 0.39, 95% confidence interval = 0.2-0.77, P =
      0.007, respectively). CONCLUSION: RT is an effective treatment option without
      serious adverse events. RT should be considered for the patients with better
      hepatic function who have invasion to IHLVs.

PMID- 23869687
TI  - Epigenetic control of skin differentiation genes by phytocannabinoids.
AB  - BACKGROUND AND PURPOSE: Endocannabinoid signalling has been shown to have a role
      in the control of epidermal physiology, whereby anandamide is able to regulate
      the expression of skin differentiation genes through DNA methylation. Here, we
      investigated the possible epigenetic regulation of these genes by several
      phytocannabinoids, plant-derived cannabinoids that have the potential to be novel
      therapeutics for various human diseases. EXPERIMENTAL APPROACH: The effects of
      cannabidiol, cannabigerol and cannabidivarin on the expression of skin
      differentiation genes keratins 1 and 10, involucrin and transglutaminase 5, as
      well as on DNA methylation of keratin 10 gene, were investigated in human
      keratinocytes (HaCaT cells). The effects of these phytocannabinoids on global DNA
      methylation and the activity and expression of four major DNA methyltransferases
      (DNMT1, 3a, 3b and 3L) were also examined. KEY RESULTS: Cannabidiol and
      cannabigerol significantly reduced the expression of all the genes tested in
      differentiated HaCaT cells, by increasing DNA methylation of keratin 10 gene, but
      cannabidivarin was ineffective. Remarkably, cannabidiol reduced keratin 10 mRNA
      through a type-1 cannabinoid (CB1 ) receptor-dependent mechanism, whereas
      cannabigerol did not affect either CB1 or CB2 receptors of HaCaT cells. In
      addition, cannabidiol, but not cannabigerol, increased global DNA methylation
      levels by selectively enhancing DNMT1 expression, without affecting DNMT 3a, 3b
      or 3L. CONCLUSIONS AND IMPLICATIONS: These findings show that the
      phytocannabinoids cannabidiol and cannabigerol are transcriptional repressors
      that can control cell proliferation and differentiation. This indicates that they
      (especially cannabidiol) have the potential to be lead compounds for the
      development of novel therapeutics for skin diseases.

PMID- 23869690
TI  - Behavioural phenotyping of casper mutant and 1-pheny-2-thiourea treated adult
      zebrafish.
AB  - The ability to visualise neural circuits in zebrafish in vivo is one of the most
      useful aspects of this model organism in neuroscience. To maintain the
      transparency of embryos, however, drugs, such as 1-pheyl-2-thiourea (PTU) must be
      added, or researchers can use mutants that do not develop pigment (e.g., the
      casper). The behavioural characteristics of such strains, however, have not been
      documented. Here, we tested adult zebrafish from the casper line, as well as wild
      type (Tubingen, TU) and wild-types treated as embryos with PTU on three commonly
      used behavioural endpoints in neuroscience: novel tank test (similar to open
      field in rodents), conditioned place preference for nicotine, and social cohesion
      (using a new method of cluster analysis). We found no differences between the
      casper and the TU, but the adult TU treated with PTU as embryos showed a marked
      increase in anxiety during the novel tank test. These data suggest that where
      possible, labs interested in analysis of developmental processes involved in
      adult phenotypes should avoid the use of PTU in favour of transparent mutants,
      such as casper.

PMID- 23869691
TI  - Luminal esophageal temperature monitoring for the prevention of esophageal injury
      during left atrial ablation: LET it be?

PMID- 23869692
TI  - A fluorine 1,2-migration via aryl cation/radical/radical anion/radical sequence.
AB  - Irradiation of a 7-piperazino-8-fluoroquinolone causes formal 1,2-fluorine
      migration, piperazine loss and reduction, or nucleophile addition in 8. Product
      study, laser flash photolysis, and computational modeling support F(-) detachment
      to yield a triplet 8-quinolyl cation that either inserts intramolecularly or is
      trapped by Cl(-), Br(-). However, iodide and pyrrole reduce it to the radical
      that continues the 'redox tour' (aryl cation-> radical-> radical anion-> radical
      and then again radical or radical anion) leading to the rearranged products. 

PMID- 23869693
TI  - Regional circadian period difference in the suprachiasmatic nucleus of the
      mammalian circadian center.
AB  - The suprachiasmatic nucleus (SCN) is the mammalian circadian rhythm center.
      Individual oscillating neurons have different endogenous circadian periods, but
      they are usually synchronized by an intercellular coupling mechanism. The
      differences in the period of each oscillating neuron have been extensively
      studied; however, the clustering of oscillators with similar periods has not been
      reported. In the present study, we artificially disrupted the intercellular
      coupling among oscillating neurons in the SCN and observed regional differences
      in the periods of the oscillating small-latticed regions of the SCN using a
      transgenic rat carrying a luciferase reporter gene driven by regulatory elements
      from a per2 clock gene (Per2::dluc rat). The analysis divided the SCN into two
      regions--aregion with periods shorter than 24 h (short-period region, SPR) and
      another with periods longer than 24 h (long-period region, LPR). The SPR was
      located in the smaller medial region of the dorsal SCN, whereas the LPR occupied
      the remaining larger region. We also found that slices containing the medial
      region of the SCN generated shorter circadian periods than slices that contained
      the lateral region of the SCN. Interestingly, the SPR corresponded well with the
      region where the SCN phase wave is generated. We numerically simulated the
      relationship between the SPR and a large LPR. A mathematical model of the SCN
      based on our findings faithfully reproduced the kinetics of the oscillators in
      the SCN in synchronized conditions, assuming the existence of clustered short
      period oscillators.

PMID- 23869694
TI  - Enantioselective direct alpha-amination of aldehydes via a photoredox mechanism:
      a strategy for asymmetric amine fragment coupling.
AB  - The direct, asymmetric alpha-amination of aldehydes has been accomplished via a
      combination of photoredox and organocatalysis. Photon-generated N-centered
      radicals undergo enantioselective alpha-addition to catalytically formed chiral
      enamines to directly produce stable alpha-amino aldehyde adducts bearing
      synthetically useful amine substitution patterns. Incorporation of a photolabile
      group on the amine precursor obviates the need to employ a photoredox catalyst in
      this transformation. Importantly, this photoinduced transformation allows direct
      and enantioselective access to alpha-amino aldehyde products that do not require
      postreaction manipulation. 

PMID- 23869695
TI  - Lymphoma and myeloma cells are highly sensitive to growth arrest and apoptosis
      induced by artesunate.
AB  - OBJECTIVES: The use of new drugs has improved the treatment of multiple myeloma
      and diffuse large B-cell lymphoma (DLBCL). Nevertheless, over time many patients
      relapse and develop resistance to treatment, and efforts are needed to overcome
      drug resistance. The widely used malaria drug artesunate has been reported to
      have antitumor activity, and we aimed to test the effects of artesunate on a
      panel of myeloma and lymphoma cells. METHODS: Myeloma and DLBCL cell lines were
      treated with artesunate in vitro. The effects of artesunate treatment were
      evaluated using ATP content measurements for proliferation and annexin
      V/propidium iodide labeling for apoptosis. Western blotting was used to look for
      artesunate-induced protein changes. In addition, we measured artesunate effects
      on patient myeloma cells in the presence of bone marrow stromal cells. RESULTS:
      Artesunate treatment efficiently inhibited cell growth and induced apoptosis in
      cell lines. Apoptosis was induced concomitantly with downregulation of MYC and
      anti-apoptotic Bcl-2 family proteins, as well as with cleavage of caspase-3. The
      IC50 values of artesunate in cell lines varied between 0.3 and 16.6 MUm.
      Furthermore, some primary myeloma cells were also sensitive to artesunate at
      doses around 10 MUm. Concentrations of this order are pharmacologically relevant
      as they can be obtained in plasma after intravenous administration of artesunate
      for malaria treatment. CONCLUSION: Our findings indicate that artesunate is a
      potential drug for treatment of multiple myeloma and DLBCL at doses of the same
      order as currently in use for treatment of malaria without serious adverse
      effects.

PMID- 23869696
TI  - Heat freezes niche evolution.
AB  - Climate change is altering phenology and distributions of many species and
      further changes are projected. Can species physiologically adapt to climate
      warming? We analyse thermal tolerances of a large number of terrestrial ectotherm
      (n = 697), endotherm (n = 227) and plant (n = 1816) species worldwide, and show
      that tolerance to heat is largely conserved across lineages, while tolerance to
      cold varies between and within species. This pattern, previously documented for
      ectotherms, is apparent for this group and for endotherms and plants, challenging
      the longstanding view that physiological tolerances of species change
      continuously across climatic gradients. An alternative view is proposed in which
      the thermal component of climatic niches would overlap across species more than
      expected. We argue that hard physiological boundaries exist that constrain
      evolution of tolerances of terrestrial organisms to high temperatures. In
      contrast, evolution of tolerances to cold should be more frequent. One
      consequence of conservatism of upper thermal tolerances is that estimated niches
      for cold-adapted species will tend to underestimate their upper thermal limits,
      thereby potentially inflating assessments of risk from climate change. In
      contrast, species whose climatic preferences are close to their upper thermal
      limits will unlikely evolve physiological tolerances to increased heat, thereby
      being predictably more affected by warming.

PMID- 23869697
TI  - Difficulties in the neuroscience of creativity: jazz improvisation and the
      scientific method.
AB  - Creativity is a fundamental and remarkable human capacity, yet the scientific
      study of creativity has been limited by the difficulty of reconciling the
      scientific method and creative processes. We outline several hurdles and
      considerations that should be addressed when studying the cognitive neuroscience
      of creativity and suggest that jazz improvisation may be one of the most useful
      experimental models for the study of spontaneous creativity. More broadly, we
      argue that studying creativity in a way that is both scientifically and
      ecologically valid requires collaboration between neuroscientists and artists. 

PMID- 23869698
TI  - Work process related to cerebral palsy of neurological rehabilitation centers.
AB  - OBJECTIVE: To evaluate the work process for CP cases in different rehabilitation
      centers according to Brazilian health policies and recommendations from the
      "World Report on Disability". METHODS: A questionnaire - Evaluation Process of
      Rehabilitation of Children with CP was applied to the Coordinators of 13
      services. This instrument has a maximum score of 108 points. RESULTS: The results
      of the questionnaire varied from 28 to 64 points. The mean and SD were 43.5 and
      10.9, respectively. The main administrative difficulties were: (a) presence of
      unmet demand, (b) patient absenteeism, (c) referral to primary care services, (d)
      inadequate physical facilities, (e) the scarce provision of prosthetics and
      orthotics, (f) insufficient financial resources, (g) human resources training,
      (h) difficulties with the use of the information system and (i) transportation
      difficulties for patients. CONCLUSION: Administrative and clinical guidelines are
      needed for uniformity of the work process of the rehabilitation centers.

PMID- 23869699
TI  - Accelerating prevention of mother-to-child transmission of HIV: ten-year
      experience of universal antenatal HIV testing programme in a low HIV prevalence
      setting in Hong Kong.
AB  - Hong Kong has a low prevalence of HIV infection at less than 0.01%. Universal
      Antenatal HIV Testing Programme (UATP) was launched in all public antenatal units
      in September 2001. In 2008, voluntary rapid HIV testing was introduced in all
      public labour units to fill up the gap for pregnant women without HIV testing
      during the antenatal period. This study evaluated the performance of UATP and
      rapid HIV testing with indicators. From September 2001 to December 2011, process
      and outcome indicators for monitoring and evaluation were collected from the
      service providers in the form of monthly return of workload statistics and case
      based statistics of each identified HIV-positive pregnancy via reporting forms. A
      total of 479,160 antenatal HIV tests and 2,675 rapid tests were performed in the
      study period. The acceptance rate for UATP and rapid HIV testing was 98% and
      80.4% respectively. With the implementation of rapid HIV testing in January 2008,
      the proportion of pregnant women with HIV status discerned before delivery
      increased from 84.9% in 2006 to over 99.5% since 2008. The HIV prevalence in UATP
      and rapid HIV testing was 0.02% and 0.1% respectively. Fifty-three (68%) out of
      78 HIV-infected pregnant women identified from the programme have delivered
      locally. Forty-three (81%) of them delivered by caesarean section and 50 (94%) of
      them were given antiretrovirals for intervention. Only three children born before
      the implementation of rapid HIV testing were HIV-infected. In conclusion, UATP
      and its rapid HIV testing component have been highly accepted and effective in
      the prevention of perinatal HIV transmission in Hong Kong. 

PMID- 23869700
TI  - Copper-vapor-assisted chemical vapor deposition for high-quality and metal-free
      single-layer graphene on amorphous SiO2 substrate.
AB  - We report that high-quality single-layer graphene (SLG) has been successfully
      synthesized directly on various dielectric substrates including amorphous SiO2/Si
      by a Cu-vapor-assisted chemical vapor deposition (CVD) process. The Cu vapors
      produced by the sublimation of Cu foil that is suspended above target substrates
      without physical contact catalyze the pyrolysis of methane gas and assist
      nucleation of graphene on the substrates. Raman spectra and mapping images reveal
      that the graphene formed on a SiO2/Si substrate is almost defect-free and
      homogeneous single layer. The overall quality of graphene grown by Cu-vapor
      assisted CVD is comparable to that of the graphene grown by regular metal
      catalyzed CVD on a Cu foil. While Cu vapor induces the nucleation and growth of
      SLG on an amorphous substrate, the resulting SLG is confirmed to be Cu-free by
      synchrotron X-ray photoelectron spectroscopy. The SLG grown by Cu-vapor-assisted
      CVD is fabricated into field effect transistor devices without transfer steps
      that are generally required when SLG is grown by regular CVD process on metal
      catalyst substrates. This method has overcome two important hurdles previously
      present when the catalyst-free CVD process is used for the growth of SLG on fused
      quartz and hexagonal boron nitride substrates, that is, high degree of structural
      defects and limited size of resulting graphene, respectively. 

PMID- 23869701
TI  - Comparison of physical activity estimates using International Physical Activity
      Questionnaire (IPAQ) and accelerometry in fibromyalgia patients: the Al-Andalus
      study.
AB  - The International Physical Activity Questionnaire (IPAQ) has been widely used to
      assess physical activity in healthy populations. The present study compared
      physical activity assessed by the long, self-administrated version of the
      International Physical Activity Questionnaire with physical activity assessed by
      accelerometry in patients with fibromyalgia. A total of 99 (five men)
      participants with fibromyalgia completed the International Physical Activity
      Questionnaire and wore an accelerometer for nine consecutive days. We analysed
      the correlations of physical activity expressed as min . day(-1) of light,
      moderate, vigorous, and moderate to vigorous (MVPA) intensity, as well as time
      spent sitting, by the International Physical Activity Questionnaire and
      accelerometry by Spearman correlations. Bland and Altman plots were performed to
      verify the agreements between both instruments. The results showed weak yet
      significant correlations (Rs = 0.15-0.39, all P < 0.05) in all physical activity
      intensities between the two instruments, except for sedentary time. The highest
      correlations were observed for physical activity at home or in garden (Rs =
      0.297, P < 0.01). The results suggest that the long self-administrated
      International Physical Activity Questionnaire is a questionable instrument to
      assess physical activity in patients with fibromyalgia. Therefore, physical
      activity measurement in fibromyalgia patients should not be limited solely to
      self-reported measures.

PMID- 23869702
TI  - Effects of pond draining on biodiversity and water quality of farm ponds.
AB  - Farm ponds have high conservation value because they contribute significantly to
      regional biodiversity and ecosystem services. In Japan pond draining is a
      traditional management method that is widely believed to improve water quality
      and eradicate invasive fish. In addition, fishing by means of pond draining has
      significant cultural value for local people, serving as a social event. However,
      there is a widespread belief that pond draining reduces freshwater biodiversity
      through the extirpation of aquatic animals, but scientific evaluation of the
      effectiveness of pond draining is lacking. We conducted a large-scale field study
      to evaluate the effects of pond draining on invasive animal control, water
      quality, and aquatic biodiversity relative to different pond-management
      practices, pond physicochemistry, and surrounding land use. The results of
      boosted regression-tree models and analyses of similarity showed that pond
      draining had little effect on invasive fish control, water quality, or aquatic
      biodiversity. Draining even facilitated the colonization of farm ponds by
      invasive red swamp crayfish (Procambarus clarkii), which in turn may have
      detrimental effects on the biodiversity and water quality of farm ponds. Our
      results highlight the need for reconsidering current pond management and
      developing management plans with respect to multifunctionality of such ponds.
      Efectos del Drenado de Estanques sobre la Biodiversidad y la Calidad del Agua en
      Estanques de Cultivo. 

PMID- 23869703
TI  - Anionic lipid binding to the foreign protein MGS provides a tight coupling
      between phospholipid synthesis and protein overexpression in Escherichia coli.
AB  - Certain membrane proteins involved in lipid synthesis can induce formation of new
      intracellular membranes in Escherichia coli, i.e., intracellular vesicles. Among
      those, the foreign monotopic glycosyltransferase MGS from Acholeplasma laidlawii
      triggers such massive lipid synthesis when overexpressed. To examine the
      mechanism behind the increased lipid synthesis, we investigated the lipid binding
      properties of MGS in vivo together with the correlation between lipid synthesis
      and MGS overexpression levels. A good correlation between produced lipid
      quantities and overexpressed MGS protein was observed when standard LB medium was
      supplemented with four different lipid precursors that have significant roles in
      the lipid biosynthesis pathway. Interestingly, this correlation was highest
      concerning anionic lipid production and at the same time dependent on the
      selective binding of anionic lipid molecules by MGS. A selective interaction with
      anionic lipids was also observed in vitro by (31)P NMR binding studies using
      bicelles prepared with E. coli lipids. The results clearly demonstrate that the
      discriminative withdrawal of anionic lipids, especially phosphatidylglycerol,
      from the membrane through MGS binding triggers an in vivo signal for cells to
      create a "feed-forward" stimulation of lipid synthesis in E. coli. By this
      mechanism, cells can produce more membrane surface in order to accommodate
      excessively produced MGS molecules, which results in an interdependent cycle of
      lipid and MGS protein synthesis. 

PMID- 23869705
TI  - Has fertility declined from mid-1990s to mid-2000s?
AB  - OBJECTIVE: To assess changes in self-reported fertility from the mid-1990s to the
      mid-2000s. DESIGN: The study is a retrospective population-based study. SETTING:
      The study applied a dataset from two cross-sectional surveys conducted in the mid
      1990s and some 10 years later, inviting all women in a county in Norway.
      POPULATION: Women aged 50-59 years enrolled in either survey constituted two
      cohorts. Data on 4468 women in the first survey (Cohort 1940) and 4951 women in
      the latter survey (Cohort 1950) were collected by structured questionnaires. MAIN
      OUTCOME MEASURES: Prevalence of fertility, infertility with subcategories
      subfertility and involuntary childlessness, as well as childlessness was
      estimated and compared between the surveys. Possible sociodemographic and
      lifestyle predictors of fertility were assessed at different points in time.
      RESULTS: Fertility declined over the two successive surveys; 87.8% of the women
      in Cohort 1940 were fertile compared with 84.2% of the women in Cohort 1950 (p =
      0.000). The prevalence of infertility increased over time due to an increase in
      subfertility from 7.8 to 10.6% (p = 0.000). The level of education increased with
      time, as did at-risk alcohol consumption and smoking, and these factors were
      adversely associated with fertility. The proportion of childless women increased
      across surveys (p = 0.004) but relatively fewer women were involuntarily
      childless in Cohort 1950 than in Cohort 1940 (p = 0.543). CONCLUSION: Fertility,
      measured at 10-year intervals, declined significantly. The decline in fertility
      was related to changes in subfertility. Adjustments for sociodemographic and
      lifestyle factors did not fully explain the decline in fertility.

PMID- 23869704
TI  - Antagonism of endogenous nociceptin/orphanin FQ inhibits infarction-associated
      ventricular arrhythmias via PKC-dependent mechanism in rats.
AB  - BACKGROUND AND PURPOSE: Evidence indicates nociceptin/orphanin FQ (N/OFQ) may
      participate in the pathology of cardiac arrhythmias associated with myocardial
      infarction. But the role of N/OFQ in the arrhythmogenesis in acute myocardial
      infarction is unclear. The aim of this study was to investigate the effects of
      endogenous N/OFQ on infarction-associated arrhythmias. EXPERIMENTAL APPROACH: The
      expression of N/OFQ, PKC activity and ventricular arrhythmias in presence and
      absence of UFP-101, a specific antagonist of N/OFQ receptor, were examined
      following permanent coronary artery occlusion in anaesthetized rats. The effect
      of N/OFQ on action potential duration was examined in isolated rat
      cardiomyocytes. KEY RESULTS: It was observed that N/OFQ was increased by 41% in
      the myocardium after coronary artery occlusion (P < 0.01 vs. control).
      Pretreatment with UFP-101 (10(-7)  mol.kg(-1) , i.v.) reduced the incidence of
      ventricular ectopic beats by 70% and ventricular tachycardia by 51% respectively
      (all P < 0.05 vs. control). Meanwhile, PKC activity was elevated in the rats
      treated with UFP-101 (by 35%, P < 0.05 vs. control). A selective PKC inhibitor,
      calphostin C, completely abolished the anti-arrhythmic effects of UFP-101 (P <
      0.01). N/OFQ (at 10(-11) , 10(-9) and 1 * 10(-7)  mol.L(-1) ) shortened the
      action potential duration by 3% (P > 0.05), 10% (P < 0.05) and 22% (P < 0.01),
      respectively, via N/OFQ receptor. CONCLUSIONS AND IMPLICATIONS: Antagonism of
      endogenous N/OFQ produces anti-arrhythmic effects on ventricular arrhythmias in
      acute myocardial infarction, possibly via modulating PKC activity and action
      potential of myocytes.

PMID- 23869706
TI  - Race, socioeconomic status, and treatment center are associated with insulin pump
      therapy in youth in the first year following diagnosis of type 1 diabetes.
AB  - BACKGROUND: Increasing numbers of children and adolescents with type 1 diabetes
      (T1D) have been placed on insulin pump therapy. Nevertheless, data are limited
      regarding patterns of pump use during the first year of treatment and the
      clinical and socioeconomic factors associated with early use of pump therapy.
      Therefore, we sought to determine factors associated with pump therapy within the
      first year of diagnosis in youth enrolled in the Pediatric Diabetes Consortium
      (PDC) T1D New-Onset (NeOn) Study. SUBJECTS AND METHODS: The NeOn Study includes
      youth <19 years old at T1D diagnosis who have been followed from the time of
      diagnosis at seven U.S. pediatric diabetes centers. Cox regression was used to
      determine factors associated with transition from injection to pump therapy
      during the first year of T1D in 1,012 participants. RESULTS: Twenty-seven percent
      (n=254) of participants began pump therapy within the first year of diagnosis,
      ranging from 18% to 59% among the seven centers. After adjusting for center
      effect, factors associated with pump use in multivariate analysis included
      private health insurance (37% vs. 7%; P<0.001), having annual household income
      over $100,000 (50% vs. 15%; P<0.001), and non-Hispanic white race (36% vs. 11%;
      P<0.001). The hemoglobin A1c level did not appear to influence the decision to
      initiate pump use. CONCLUSIONS: Participants of non-Hispanic white race and
      higher socioeconomic status were more likely to be placed on pumps during the
      first year. Further investigations are needed to gain a better understanding of
      barriers to use of pumps in youth with T1D, especially in disadvantaged and
      minority families.

PMID- 23869707
TI  - Bisphosphonate-related osteonecrosis of the jaws and its relevance to children--a
      review.
AB  - Bisphosphonate-related osteonecrosis of the jaws (BRONJ) has been detailed
      extensively in adults, but to date, there have been no similar cases in children.
      Members of the dental team may treat children prescribed bisphosphonate therapy
      often for management of osteogenesis imperfecta (OI). There is uncertainty as to
      how best treat this patient group. This review explores the background of
      bisphosphonates, indications for their prescription in children, adverse effects
      with special emphasis on BRONJ, and protocols available to guide dental
      management. 

PMID- 23869709
TI  - Historical biogeography of the Isthmus of Panama.
AB  - About 3 million years ago (Ma), the Isthmus of Panama joined the Americas,
      forming a land bridge over which inhabitants of each America invaded the other
      the Great American Biotic Interchange. These invasions transformed land
      ecosystems in South and Middle America. Humans invading from Asia over 12000
      years ago killed most mammals over 44 kg, again transforming tropical American
      ecosystems. As a sea barrier, the isthmus induced divergent environmental change
      off its two coasts-creating contrasting ecosystems through differential
      extinction and diversification. Approximately 65 Ma invading marsupials and
      ungulates of North American ancestry, and xenarthrans of uncertain provenance
      replaced nearly all South America's non-volant mammals. There is no geological
      evidence for a land bridge at that time. Together with rodents and primates
      crossing from Africa 42 to 30 Ma, South America's mammals evolved in isolation
      until the interchange's first heralds less than 10 Ma. Its carnivores were
      ineffective marsupials. Meanwhile, North America was invaded by more competitive
      Eurasian mammals. The Americas had comparable expanses of tropical forest 55 Ma;
      later, climate change confined North American tropical forest to a far smaller
      area. When the isthmus formed, North American carnivores replaced their marsupial
      counterparts. Although invaders crossed in both directions, North American
      mammals spread widely, diversified greatly, and steadily replaced South American
      open-country counterparts, unused to effective predators. Invading South American
      mammals were less successful. South America's birds, bats, and smaller rainforest
      mammals, equally isolated, mostly survived invasion. Its vegetation, enriched by
      many overseas invaders, remained intact. This vegetation resists herbivory
      effectively. When climate permitted, South America's rainforest, with its bats,
      birds and mammals, spread to Mexico. Present-day tropical American vegetation is
      largely zoned by trade-offs between exploiting well-watered settings versus
      surviving droughts, exploiting fertile versus coping with poor soil, and
      exploiting lowland warmth versus coping with cooler altitudes. At the start of
      the Miocene, a common marine biota extended from Trinidad to Ecuador and western
      Mexico, which evolved in isolation from the Indo-Pacific until the Pleistocene.
      The seaway between the Americas began shoaling over 12 Ma. About 10 Ma the land
      bridge was briefly near-complete, allowing some interchange of land mammals
      between the continents. By 7 Ma, the rising sill had split deeper-water
      populations. Sea temperature, salinity and sedimentary carbon content had begun
      to increase in the Southern Caribbean, but not the Pacific. By 4 Ma, the seaway's
      narrowing began to extinguish Caribbean upwellings. By 2 Ma, upwellings remained
      only along Venezuela; Caribbean plankton, suspension-feeding molluscs and their
      predators had declined sharply, largely replaced by bottom-dwelling corals and
      calcareous algae and magnificent coral reefs. Closing the seaway extinguished the
      Eastern Pacific's reef corals (successors recolonized from the Indo-Pacific 6000
      years ago), whereas many molluscs of productive waters that once thrived in the
      Caribbean now survive only in the Eastern Pacific. The present-day productive
      Eastern Pacific, with few, small coral reefs and a plankton-based ecosystem
      contrasts with the Caribbean, whose clear water favours expansive coral reefs and
      bottom-dwelling primary producers. These ecosystems reflect the trade-off between
      fast growth and effective defence with attendant longevity. Overfishing with new
      technologies during the last few centuries, however, has caused population
      crashes of ever-smaller marine animals, devastating Caribbean ecosystems.

PMID- 23869710
TI  - Influence of vascular risk factors and neuropsychological profile on functional
      performances in CADASIL: results from the MIcrovascular LEukoencephalopathy Study
      (MILES).
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel
      disease that may lead to disability and whose phenotype modulators are still
      unknown. METHODS: In the MIcrovascular LEukoencephalopathy Study (MILES), we
      assessed the influence of vascular risk factors and the effect of different
      cognitive domains (memory, psychomotor speed and executive functions)
      performances on functional abilities in CADASIL in comparison with age-related
      leukoencephalopathy (ARL). RESULTS: We evaluated 51 CADASIL patients (mean age
      50.3 +/- 13.8 years, 47.1% males) and 68 ARL patients (70.6 +/- 7.4 years, 58.8%
      males). Considering vascular risk factors, after adjustment for age, CADASIL
      patients had higher mean BMI values than ARL patients. Stroke history frequency
      was similar in the two groups. After adjustment for age, more CADASIL patients
      were disabled (impaired on >= 2 items of the Instrumental Activities of Daily
      Living scale) in comparison with ARL patients, and CADASIL patients had worse
      functional performances evaluated with the Disability Assessment for Dementia
      (DAD) scale. In CADASIL patients, hypertension was related to both DAD score and
      disability. The cognitive profile of CADASIL and ARL patients was similar, but on
      a stepwise linear regression analysis functional performances were mainly
      associated with the memory index (beta = -0.418, P < 0.003) in CADASIL patients
      and the executive function index (beta = -0.321, P = 0.028) in ARL. CONCLUSIONS:
      This study suggests that hypertension may contribute to functional impairment in
      CADASIL and that memory impairment has a large influence on functional decline in
      contrast with that observed in a sample of subjects with ARL.

PMID- 23869712
TI  - Catalytic asymmetric three-component 1,3-dipolar cycloaddition of aldehydes,
      hydrazides, and alkynes.
AB  - Catalytic asymmetric 1,3-dipolar cycloadditions offer expeditious ways to afford
      synthetically important chiral heterocycles. Although a variety of 1,3-dipoles
      can be employed in this context, the use of acyclic azomethine imines as a facile
      means to give chiral pyrazolines and pyrazolidines remains completely unexplored.
      We report herein the first catalytic asymmetric 1,3-dipolar cycloaddition of
      terminal alkynes with acyclic azomethine imines generated in situ from the
      corresponding aldehydes and hydrazides, which was realized using Cu(I)/pybox and
      axially chiral dicarboxylic acid cocatalysts. 

PMID- 23869711
TI  - The burden of invasive pneumococcal disease in children with underlying risk
      factors in North America and Europe.
AB  - BACKGROUND: Characterisation of risk groups who may benefit from pneumococcal
      vaccination is essential for the generation of recommendations and policy.
      METHODS: We reviewed the literature to provide information on the incidence and
      risk of invasive pneumococcal disease (IPD) in at-risk children in Europe and
      North America. The PubMed database was searched using predefined search terms and
      inclusion/exclusion criteria for papers reporting European or North American data
      on the incidence or risk of IPD in children with underlying medical conditions.
      RESULTS: Eighteen references were identified, 11 from North America and 7 from
      Europe, with heterogeneous study methods, periods and populations. The highest
      incidence was seen in US children positive for human immunodeficiency virus
      infection, peaking at 4167 per 100,000 patient-years in 2000. Studies
      investigating changes in incidence over time reported decreases in the incidence
      of IPD between the late 1990s and early 2000s. The highest risk of IPD was
      observed in children with haematological cancers or immunosuppression. Overall,
      data on IPD in at-risk children were limited, lacking incidence data for a wide
      range of predisposing conditions. There was, however, a clear decrease in the
      incidence of IPD in at-risk children after the introduction of 7-valent
      pneumococcal conjugate vaccine into immunisation programmes, as previously
      demonstrated in the general population. CONCLUSION: Despite the heterogeneity of
      the studies identified, the available data show a substantial incidence of IPD in
      at-risk children, particularly those who are immunocompromised. Further research
      is needed to determine the true risk of IPD in at-risk children, particularly in
      the post-PCV period, and to understand the benefits of vaccination and optimal
      vaccination schedules.

PMID- 23869713
TI  - Prevalence and risk factors of fatty liver disease in young and middle-aged
      population: one center study in Southwestern China.
AB  - BACKGROUND AND AIM: Fatty liver disease has become common hepatic disease not
      only in western countries but also in developing countries in Asia-Pacific area.
      Our aim was to determine the prevalence and risk factors of fatty liver disease
      as well as its correlation with metabolic syndrome in young and middle-aged
      population. METHODS: Data were collected from check-up center at the 1st
      Affiliated Hospital of Chongqing Medical University in 2011. Relationships of
      fatty liver disease and age, body mass index, and metabolic syndrome were
      determined. Logistic regression was performed to identify the risk factors for
      fatty liver disease. RESULTS: Data of 18 676 subjects (mean age 40.55 +/- 9.94
      ranging from 18 to 59) were analyzed. The prevalence of fatty liver disease was
      22.0% and increased along with age, body mass index, and the presence and
      severity of metabolic syndrome. In logistic regression, living area was
      significantly associated with fatty liver in total population. Male, overweight
      and obese, waist-to-height ratio >= 0.5, hypertension, hypercholesterolemia, high
      triglyceride, low high-density lipoprotein cholesterol, and fasting plasma
      glucose >= 7.0 mmol/L were common independent risk factors for fatty liver
      disease in urban and rural areas. Older age and white blood cell over 5.5 *10(9)
      /L were related to fatty liver disease in urban area. Obesity was the most
      important factors in both areas. CONCLUSION: Fatty liver disease was prevalent in
      young and middle-aged population and mainly associated to multiple metabolic
      disorders.

PMID- 23869714
TI  - Marine biofilms on artificial surfaces: structure and dynamics.
AB  - The search for new antifouling (AF) coatings that are environmentally benign has
      led to renewed interest in the ways that micro-organisms colonize substrates in
      the marine environment. This review covers recently published research on the
      global species composition and dynamics of marine biofilms, consisting mainly of
      bacteria and diatoms found on man-made surfaces including AF coatings. Marine
      biofilms directly interact with larger organisms (macrofoulers) during
      colonization processes; hence, recent literature on understanding the basis of
      the biofilm/macrofouling interactions is essential and will also be reviewed
      here. Overall, differences have been identified in species composition between
      biofilm and planktonic forms for both diatoms and bacteria at various exposure
      sites. In most studies, the underlying biofilm was found to induce larval and
      spore settlement of macrofoulers; however, issues such as reproducibility,
      differences in exposure sites and biofilm composition (natural multispecies vs.
      monospecific species) may influence the outcomes. 

PMID- 23869715
TI  - Synthesis, magnetism, and electrochemistry of the Ni14- and Ni5-containing
      heteropolytungstates [Ni14(OH)6(H2O)10(HPO4)4(P2W15O56)4]34- and
      [Ni5(OH)4(H2O)4(beta-GeW9O34)(beta-GeW8O30(OH))]13-.
AB  - The two Ni(2+)-containing heteropolytungstates
      [Ni14(OH)6(H2O)10(HPO4)4(P2W15O56)4](34-) (Ni14) and [Ni5(OH)4(H2O)4(beta
      GeW9O34)(beta-GeW8O30(OH))](13-) (Ni5) have been successfully synthesized in
      aqueous, basic media under conventional reaction conditions, and they were
      characterized by single-crystal X-ray diffraction, IR spectroscopy,
      thermogravimetric and elemental analyses, electrochemistry, and magnetic studies.
      The cyclic voltammetry (CV) patterns of Ni14 and Ni5 showed chemically reversible
      multielectronic waves for slow scan time scales. For Ni14, an important acidity
      inversion effect between its reduced forms was observed. Magnetic studies
      revealed dominant ferromagnetic interactions among the nickel(II) ions in both
      polyanions. 

PMID- 23869716
TI  - Differences in testing, stigma, and perceived consequences of stigmatization
      among heterosexual men and women living with HIV in Bengaluru, India.
AB  - Approximately 2.4 million people in India are living with HIV. Gender inequality
      affects HIV prevention, detection, and management. The purpose of this paper was
      to describe gender differences in the experience of living with HIV in Bengaluru,
      India. A subsample of n = 313 (159 men and 154 women) from a larger cohort was
      used for these analyses. Participants were recruited through AIDS service
      organizations. They completed an interviewer-administered survey assessing HIV
      testing experience, types of stigma, and perceived consequences of
      stigmatization. The majority of men (67%) reported getting HIV tested because of
      illness, while women were more likely to be tested after learning their spouse's
      HIV-positive status (42%). More men (59%) than women (45%, p<0.05) were tested in
      private care settings. Men reported significantly higher mean levels of
      internalized stigma (men: M=0.71, SD = 0.63; women: M=0.46, SD = 0.55; p<0.001),
      whereas the women reported significantly higher scores for enacted stigma (men:
      M=1.30, SD = 1.69; women: M=2.10, SD = 2.17; p<0.001). These differences remained
      significant after controlling for potential socio-demographic covariates.
      Following their diagnosis, more women reported moving out of their homes (men:
      16%; women: 26%; p<0.05). More men (89%) than women (66%; p<0.001) reported to
      have modified their sexual behavior after being diagnosed. These findings suggest
      that the experience of living with HIV and HIV stigma varies by gender in this
      population. Suggestions for a gender-based approach to HIV prevention and stigma
      reduction are provided.

PMID- 23869718
TI  - Phrenic nerve injury: An underrecognized and potentially preventable complication
      of pulmonary vein isolation using a wide-area circumferential ablation approach.
AB  - INTRODUCTION: Phrenic nerve injury (PNI) is a well-known, although uncommon,
      complication of pulmonary vein isolation (PVI) using radiofrequency energy.
      Currently, there is no consensus about how to avoid or minimize this injury. The
      purpose of this study was to determine how often the phrenic nerve, as identified
      using a high-output pacing, lies along the ablation trajectory of a wide-area
      circumferential lesion set. We also sought to determine if PVI can be achieved
      without phrenic nerve injury by modifying the ablation lesion set so as to avoid
      those areas where phrenic nerve capture (PNC) is observed. METHODS AND RESULTS:
      We prospectively enrolled 100 consecutive patients (age 61.7 +/- 9.2 years old,
      75 men) who underwent RF PVI using a wide-area circumferential ablation approach.
      A high-output (20 mA at 2 milliseconds) endocardial pacing protocol was performed
      around the right pulmonary veins and the carina where a usual ablation lesion set
      would be made. A total of 30% of patients had PNC and required modification of
      ablation lines. In the group of patients with PNC, the carina was the most common
      site of capture (85%) followed by anterior right superior pulmonary vein (RSPV)
      (70%) and anterior right inferior pulmonary vein (RIPV) (30%). A total of 25% of
      PNC group had capture in all 3 (RSPV, RIPV, and carina) regions. There was no
      difference in the clinical characteristics between the groups with and without
      PNC. RF PVI caused no PNI in either group. CONCLUSION: High output pacing around
      the right pulmonary veins and the carina reveals that the phrenic nerve lies
      along a wide-area circumferential ablation trajectory in 30% of patients.
      Modification of ablation lines to avoid these sites may prevent phrenic nerve
      injury during RF PVI.

PMID- 23869720
TI  - Asymmetric total synthesis of (+)-fusarisetin A via the intramolecular Pauson
      Khand reaction.
AB  - An asymmetic total synthesis of (+)-fusarisetin A has been achieved. The
      essential to our strategy was the application of the intramolecular Pauson-Khand
      reaction for the stereoselective construction of the trans-decalin subunit of (+)
      fusarisetin A with a unique C16 quarternary chiral center. The developed
      chemistry offers an alternative to the IMDA reaction that has been used for
      fusarisetin A, and is applicable to analogue synthesis for biological evaluation.

PMID- 23869717
TI  - The complex relationship between the light-entrainable and methamphetamine
      sensitive circadian oscillators: evidence from behavioral studies of Period
      mutant mice.
AB  - The methamphetamine-sensitive circadian oscillator (MASCO) is an enigmatic
      circadian clock whose output is observed during continuous consumption of low
      dose methamphetamine. The MASCO rhythm persists when the light-entrainable
      pacemaker in the suprachiasmatic nucleus (SCN) is lesioned, but the anatomical
      location of MASCO is unknown. We recently found that the period of the MASCO
      rhythm is unusually short (21 h) in mice with disruption of all three paralogs of
      the canonical clock gene, Period. In this study, we investigated the contribution
      of each Period paralog to timekeeping in MASCO. We measured wheel-running
      activity rhythms in intact and SCN-lesioned Per1-, 2- and 3-mutant mice
      administered methamphetamine, and found that none of the mice displayed a short
      (21-h) period, demonstrating that no single Period gene is responsible for the
      short-period MASCO rhythm of Per1(-/-) /Per2(-/-) /Per3(-/-) mice. We also found
      that the periods of activity rhythms in constant darkness were lengthened by
      methamphetamine treatment in intact wild-type, Per1(-/-) and Per3(-/-) mice but
      not Per2(-/-) mice, and Per2(-/-) mice had two distinct activity rhythms upon
      release to constant light. These data suggest that the SCN and MASCO are not
      coupled in Per2(-/-) mice. The MASCO rhythm in Per1(-/-) /Per2(-/-) mice in
      constant darkness alternated between a short (22-h) and a long (27-h) period.
      This pattern could result from two coupled oscillators that are not synchronised
      to each other, or from a single oscillator displaying birhythmicity. Finally, we
      propose a working model of the in vivo relationship between MASCO and the SCN
      that poses testable hypotheses for future studies. 

PMID- 23869721
TI  - A single course of all-trans retinoic acid plus arsenic trioxide reached a long
      term survival in a patient with newly diagnosed acute promyelocytic leukemia: a
      suggestion for reduction of treatment courses?

PMID- 23869722
TI  - Design and synthesis of polymer-functionalized NIR fluorescent dyes--magnetic
      nanoparticles for bioimaging.
AB  - The fluorescent probes having complete spectral separation between absorption and
      emission spectra (large Stokes shift) are highly useful for solar concentrators
      and bioimaging. In bioimaging application, NIR fluorescent dyes have a greater
      advantage in tissue penetration depth compared to visible-emitting organic dyes
      or inorganic quantum dots. Here we report the design, synthesis, and
      characterization of an amphiphilic polymer, poly(isobutylene-alt-maleic anhyride)
      functionalized near-infrared (NIR) IR-820 dye and its conjugates with iron oxide
      (Fe3O4) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR)
      imaging. Our results demonstrate that the Stokes shift of unmodified dye can be
      tuned (from ~106 to 208 nm) by the functionalization of the dye with polymer and
      MNPs. The fabrication of bimodal probes involves (i) the synthesis of NIR
      fluorescent dye (IR-820 cyanine) functionalized with ethylenediamine linker in
      high yield, >90%, (ii) polymer conjugation to the functionalized NIR fluorescent
      dye, and (iii) grafting the polymer-conjugated dyes on iron oxide MNPs. The
      resulting uniform, small-sized (ca. 6 nm) NIR fluorescent dye-magnetic hybrid
      nanoparticles (NPs) exhibit a wider emissive range (800-1000 nm) and minimal
      cytotoxicity. Our preliminary studies demonstrate the potential utility of these
      NPs in bioimaging by means of direct labeling of cancerous HeLa cells via NIR
      fluorescence microscopy and good negative contrast enhancement in T2-weighted MR
      imaging of a murine model.

PMID- 23869723
TI  - Examination of the relationship between body mass index (BMI) and functional
      independence level in children with spina bifida.
AB  - OBJECTIVE: The aim of this study is to examine the relationship between body mass
      index (BMI) and functional independence level in children with spina bifida (SB).
      METHODS: The study included 116 children between 5 and 18 years. Subjects' socio
      demographic characteristics, BMI values and functional independence levels were
      recorded. RESULTS: There was negative correlation between BMI and communication
      and social cognition in girls (p < 0.05). No correlation was found between BMI
      and WeeFIM in boys (p > 0.05). CONCLUSION: The results indicated that body weight
      in children with SB affected functional independency and that precautions to
      control weight important in these children.

PMID- 23869724
TI  - Economic and ecological outcomes of flexible biodiversity offset systems.
AB  - The commonly expressed goal of biodiversity offsets is to achieve no net loss of
      specific biological features affected by development. However, strict equivalency
      requirements may complicate trading of offset credits, increase costs due to
      restricted offset placement options, and force offset activities to focus on
      features that may not represent regional conservation priorities. Using the oil
      sands industry of Alberta, Canada, as a case study, we evaluated the economic and
      ecological performance of alternative offset systems targeting either
      ecologically equivalent areas (vegetation types) or regional conservation
      priorities (caribou and the Dry Mixedwood natural subregion). Exchanging
      dissimilar biodiversity elements requires assessment via a generalized metric; we
      used an empirically derived index of biodiversity intactness to link offsets with
      losses incurred by development. We considered 2 offset activities: land
      protection, with costs estimated as the net present value of profits of petroleum
      and timber resources to be paid as compensation to resource tenure holders, and
      restoration of anthropogenic footprint, with costs estimated from existing
      restoration projects. We used the spatial optimization tool MARXAN to develop
      hypothetical offset networks that met either the equivalent-vegetation or
      conservation-priority targets. Networks that required offsetting equivalent
      vegetation cost 2-17 times more than priority-focused networks. This finding
      calls into question the prudence of equivalency-based systems, particularly in
      relatively undeveloped jurisdictions, where conservation focuses on limiting and
      directing future losses. Priority-focused offsets may offer benefits to industry
      and environmental stakeholders by allowing for lower-cost conservation of valued
      ecological features and may invite discussion on what land-use trade-offs are
      acceptable when trading biodiversity via offsets. Resultados Economicos y
      Ecologicos de Sistemas de Compensacion de Biodiversidad Flexible Habib et al. 

PMID- 23869725
TI  - Eczema and ceramides: an update.
AB  - Although normal epidermal barrier function depends on numerous factors, including
      corneocytes, lipids, enzymes, pH, and calcium gradient, the key players are
      lipids and proteins in the stratum corneum. Atopic dermatitis is characterized by
      barrier abnormalities, such as the presence of filaggrin mutations in almost 50%
      of patients with moderate/severe atopic dermatitis, and lipid disturbances,
      mainly expressed as insufficient ceramides. In this review, with an emphasis on
      human studies, we consider the latest research on ceramides, on ceramides in
      different types of eczema and following various types of treatment. We also
      consider the genetic influence on stratum corneum lipids. The review is an update
      on research indexed in PubMed following the discovery of the filaggrin mutations
      in atopic dermatitis in 2006, but when newer publications cannot stand alone, we
      include publications from before 2006. 

PMID- 23869726
TI  - Risk factors associated with sensitization to hydroxyisohexyl 3-cyclohexene
      carboxaldehyde.
AB  - BACKGROUND: Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) is a synthetic
      fragrance chemical and an important contact allergen, at least in Europe. Despite
      this importance, little is known about risk factors associated with this
      allergen. OBJECTIVE: To examine factors from the history and clinical
      presentation of patch tested patients associated with HICC sensitization.
      METHODS: Contact allergy surveillance data of 95 637 patients collected by the
      Information Network of Departments of Dermatology (IVDK, www.ivkd.org) in 2002
      2011 were analysed. Point and interval estimates of the relative risk were
      derived from multifactorial logistic regression modelling. RESULTS: The overall
      prevalence of HICC sensitization was 2.24%. The strongest risk factors were
      polysensitization and dermatitis of the axillae, followed by dermatitis at other
      sites. No consistent and significant time trend was observed in this analysis. As
      compared with the youngest patients, the odds of HICC sensitization increased
      approximately three-fold in the 52-67-year age group, and strongly declined with
      further increasing age. CONCLUSIONS: The risk pattern with regard to age and
      affected anatomical site differed from that observed with other fragrance
      screening allergens. Cosmetic exposure, as broadly defined here, was a stronger
      and more prevalent individual risk factor than occupational exposure.

PMID- 23869727
TI  - Contact dermatitis caused by iodopropynyl butylcarbamate in Denmark.
AB  - BACKGROUND: Iodopropynyl butylcarbamate (IPBC) is a preservative that may cause
      contact allergy. The first cases were reported in 1997, and IPBC is currently
      included in our extended European baseline series in Denmark. OBJECTIVES: To
      assess trends during the period 2000-2011 concerning IPBC allergy in Denmark, and
      to address the question of the significance of concomitant reactions to the
      thiuram mix. PATIENTS/MATERIALS/METHODS: Nine thousand seven hundred and fifty
      five (6449 female; 3306 male) patients were patch tested with IPBC and the
      European baseline series at Gentofte Hospital during 2000-2011. The results were
      registered in an anonymized database, and analyzed with spssTM. RESULTS: Fifty
      four cases of IPBC contact allergy were detected. A significant rising trend
      during 2000-2011 was observed, with no significant changes during 2006-2011.
      MOAHLFA index analysis showed that IPBC contact allergy was, in our cohort,
      significantly more prevalent among male patients, occupational, related to hand
      eczema, and more frequent among patients over 40 years old. A significant
      relationship between IPBC and thiuram mix allergy was found. CONCLUSIONS: IPBC
      continues to be among the less frequent allergens. A 0.2% concentration in patch
      testing has contributed to the diagnosis of more sensitizations to this
      substance. Further studies are needed to clarify the reason for the over
      representation of thiuram allergy in patients sensitized to IPBC.

PMID- 23869728
TI  - What do patients with occupational hand eczema know about skin care?
AB  - BACKGROUND: The aim of the present study was to examine the knowledge of skin
      care and treatment of hand eczema (HE) in a sample of patients with newly
      reported occupational HE. MATERIALS AND METHODS: A questionnaire consisting of 13
      questions about knowledge of skin care and treatment of HE was sent to all
      patients with occupational HE reported to the National Board of Industrial
      Injuries in the period 1 January 2010 to 31 March 2010. RESULTS: Three hundred
      and seventy individuals, 269 females and 101 males, with a mean age of 39.9
      years, responded to the questionnaire (response rate of 73%). The overall
      percentage of correct answers was 73%. Variables significantly influencing the
      level of knowledge were sex and age, with a need for more information in males
      and in patients above the age of 50 years. No significant influence of level of
      education, eczema activity, previous information about HE, previous or current
      atopic eczema or dermatology life quality index (DLQI) was found. CONCLUSION:
      There is still potential for improvement of the level of knowledge among patients
      with occupational HE. Special attention should be paid to males and patients
      above the age of 50 years.

PMID- 23869729
TI  - Cost of illness from occupational hand eczema in Germany.
AB  - BACKGROUND: There is little knowledge about the costs of occupational hand
      eczema. OBJECTIVES: To estimate the societal costs of patients with occupational
      hand eczema in Germany. METHODS: Resource use during the past year, disease
      severity and quality of life [Dermatology Life Quality Index (DLQI)] were
      gathered for patients with occupational hand eczema before they entered a special
      rehabilitation programme. Costs were calculated from the societal perspective.
      The analysis focused on all patients and the severity groups no signs/mild (group
      A) and moderate to severe (group B). RESULTS: One hundred and fifty-one patients
      were analysed, with a mean age of 44.9~years and a mean DLQI score of 10.9; 64.9%
      were male. Sickness absence was recorded for 62.9% of all patients (76.4~days on
      average in the last 12~months). Annual societal costs were ?8799 per patient.
      Indirect costs represented 70% of total costs. Quality of life (DLQI) was
      statistically different across both severity groups (group A, 7.9; group B,
      12.9), but direct treatment costs were not (?2705 versus ?2610, respectively).
      There was a trend towards higher indirect costs in patients in severity group B
      (group A, ?5120; group B, ?6796). CONCLUSION: The annual societal costs of
      patients with occupational hand eczema in this study are high, and similar to
      those for severe psoriasis and atopic dermatitis.

PMID- 23869730
TI  - Comparison of four methods for assessment of severity of hand eczema.
AB  - BACKGROUND: Several instruments for the assessment of the severity of hand eczema
      and health-related quality of life (HR-QoL) related to hand eczema have been
      developed. OBJECTIVES: The aim of the present study was to evaluate the
      correlation between frequently used methods. METHODS: Consecutive patients with
      current hand eczema from three different centres participated in the study.
      Severity of hand eczema was assessed with the Hand Eczema Severity Index (HECSI),
      the Physician Global Assessment (PGA), the Clinical Photo Guide, and the
      Dermatology Life Quality Index (DLQI). RESULTS: One hundred and nineteen patients
      with hand eczema were included in the study. All six pairwise correlation
      coefficients between the tested methods were highly statistically significant.
      Correlation was highest between the HECSI and the PGA (r = 0.82), and weakest,
      although still statistically significant, between the DLQI and the other three
      severity scores (r between 0.30 and 0.45). Age and frequency of eruptions did not
      influence the correlations. With respect to sex, there was a tendency for
      correlation between methods to be higher for men than for women. CONCLUSION: We
      found an overall positive correlation between the four severity assessments
      applied. As the weakest correlation was found between the DLQI and the other
      methods, it is suggested that measurement of HR-QoL should be included for
      assessment of the severity and consequences of hand eczema, but the finding also
      indicates that a disease-specific tool for evaluation of HR-QoL in hand eczema
      patients is needed.

PMID- 23869731
TI  - A simple tool with which to study the course of chronic hand eczema in clinical
      practice: a reduced-item score.
AB  - BACKGROUND: Physicians need a simple, disease-specific tool with which to assess
      disease severity and the effect of therapeutic intervention in patients with
      chronic hand eczema. The currently available clinical scoring systems include
      numerous items, which makes them laborious to complete and limit their use in
      daily practice. OBJECTIVE: To develop a simple tool with which to assess disease
      severity of patients with chronic hand eczema. METHODS: We evaluated two tools,
      the Hand Eczema Severity Index (HECSI) and the Hand Eczema Area and Severity
      score, to determine their ability to predict the Investigator's Global Assessment
      (IGA) of disease severity in patients with moderate to severe hand eczema. We
      used a stepwise reduction analysis to determine a minimal set of significantly
      contributing items for predicting IGA. RESULTS: A three-item score, based on the
      highest observed value of induration, fissuring, and scaling, predicted IGA with
      a correlation of 0.667. The HECSI predicted the IGA with a correlation of 0.675.
      CONCLUSION: On the basis of this analysis, we propose a simple tool for clinical
      decision-making and evaluation of therapeutic intervention in daily practice.

PMID- 23869732
TI  - Allergic contact dermatitis caused by N,N-diethyl-p-phenylenediamine used in
      water quality analysis.

PMID- 23869733
TI  - Severe acute irritant contact dermatitis presenting as exfoliative erythroderma.

PMID- 23869734
TI  - Contact allergy to western red cedar in sauna furnishing.

PMID- 23869735
TI  - Contact allergy to isocyanates after accidental spillage.

PMID- 23869736
TI  - Photoallergic contact dermatitis caused by benzophenones in magazine inks.

PMID- 23869737
TI  - Contact cheilitis caused by candelilla wax contained in lipstick.

PMID- 23869738
TI  - Renin angiotensin system blockage associates with insertion/deletion polymorphism
      of angiotensin-converting enzyme in patients with hypertensive emergency.
AB  - Hypertensive crisis (HC) stands out as a form of acute elevation of blood
      pressure (BP). It can manifest itself as hypertensive emergency (HE) or
      hypertensive urgency (HU), which is usually accompanied with levels of diastolic
      BP >=120 mmHg. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D)
      polymorphism may influence manifestations of HC. Thus, this study evaluated the
      influence of ACE I/D polymorphism in individuals with HC. A total of 187 patients
      admitted with HC (HU [n=69] and HE [n=118]) and 75 normotensive individuals were
      included in the study. Peripheral blood was drawn for a biochemical and genetic
      analysis of the ACE I/D polymorphism by Polymerase Chain Reaction. HC group
      showed higher systolic BP, body mass index (BMI), glycemia, creatinine, and lower
      high-density lipoprotein (HDL) cholesterol compared with normotensive
      individuals. The use of renin-angiotensin system (RAS) blockers was more frequent
      in the HU group than in the HE group (p=0.020). The II genotype was more
      predominant in normotensive and HU individuals than among HE individuals (18.7%,
      11.6%, and 2.5%, respectively; p=0.004). Higher BMI and glycemia were associated
      with HC in the logistic regression model. ACE II genotype (odds ratio [OR] 0.14;
      95% confidence interval [CI] 0.04-0.51) and HDL cholesterol were protective for
      the development of HE. ACE II genotype was present in the HU group, compared with
      the HE group (OR 0.18; 95% CI 0.04-0.88). This study shows an association between
      the low prevalence of ACE I/D polymorphism II genotype and a greater occurrence
      of HE in Brazilian individuals. The lower blockage of RAS, which was detected in
      the HE group, may interact with the low frequency of II genotype, conferring an
      increased risk for HE.

PMID- 23869739
TI  - How can we make measures of psychotic depression symptoms more clinically useful?

PMID- 23869740
TI  - Early postnatal motor experience shapes the motor properties of C57BL/6J adult
      mice.
AB  - This study aimed to evaluate the long-term consequences of early motor training
      on the muscle phenotype and motor output of middle-aged C57BL/6J mice. Neonatal
      mice were subjected to a variety of motor training procedures, for 3 weeks during
      the period of acquisition of locomotion. These procedures are widely used for
      motor training in adults; they include enriched environment, forced treadmill,
      chronic centrifugation, and hindlimb suspension. At 9 months, the mice reared in
      the enriched environment showed a slower type of fibre in slow muscles and a
      faster type in fast muscles, improved performance in motor tests, and a modified
      gait and body posture while walking. The proportion of fibres in the postural
      muscles of centrifuged mice did not change, but these mice showed improved
      resistance to fatigue. The suspended mice showed increased persistence of
      immature hybrid fibres in the tibialis, with a slower shift in the load-bearing
      soleus, without any behavioural changes. The forced treadmill was very stressful
      for the mice, but had limited effects on motor output, although a slower profile
      was observed in the tibialis. These results support the hypothesis that motor
      experience during a critical period of motor development shapes muscle phenotype
      and motor output. The different impacts of the various training procedures
      suggest that motor performance in adults can be optimized by appropriate training
      during a defined period of motor development.

PMID- 23869741
TI  - A longitudinal study of lexical development in children learning Vietnamese and
      English.
AB  - This longitudinal study modeled lexical development among children who spoke
      Vietnamese as a first language (L1) and English as a second language (L2).
      Participants (n = 33, initial mean age of 7.3 years) completed a total of eight
      tasks (four in each language) that measured vocabulary knowledge and lexical
      processing at four yearly time points. Multivariate hierarchical linear modeling
      was used to calculate L1 and L2 trajectories within the same model for each task.
      Main findings included (a) positive growth in each language, (b) greater gains in
      English resulting in shifts toward L2 dominance, and (c) different patterns for
      receptive and expressive domains. Timing of shifts to L2 dominance underscored L1
      skills that are resilient and vulnerable to increases in L2 proficiency.

PMID- 23869742
TI  - Microsolvation of the potassium ion with aromatic rings: comparison between
      hexafluorobenzene and benzene.
AB  - We employ a recently developed methodology to study structural and energetic
      properties of the first solvation shells of the potassium ion in nonpolar
      environments due to aromatic rings, which is important to understand the
      selectivity of several biochemical phenomena. Our evolutionary algorithm is used
      in the global optimization study of clusters formed of K(+) solvated with
      hexafluorobenzene (HFBz) molecules. The global intermolecular interaction for
      these clusters has been decomposed in HFBz-HFBz and in K(+)-HFBz contributions,
      using a potential model based on different decompositions of the molecular
      polarizability of hexafluorobenzene. Putative global minimum structures of
      microsolvation clusters up to 21 hexafluorobenzene molecules were obtained and
      compared with the analogous K(+)-benzene clusters reported in our previous work
      (J. Phys. Chem. A 2012, 116, 4947-4956). We have found that both K(+)-(Bz)n and
      K(+)-(HFBz)n clusters show a strong magic number around the closure of the first
      solvation shell. Nonetheless, all K(+)-benzene clusters have essentially the same
      first solvation shell geometry with four solvent molecules around the ion,
      whereas the corresponding one for K(+)-(HFBz)n is completed with nine HFBz
      species, and its structural motif varies as n increases. This is attributed to
      the ion-solvent interaction that has a larger magnitude for K(+)-Bz than in the
      case of K(+)-HFBz. In addition, the ability of having more HFBz than Bz molecules
      around K(+) in the first solvation shell is intimately related to the inversion
      in the sign of the quadrupole moment of the two solvent species, which leads to a
      distinct ion-solvent geometry of approach. 

PMID- 23869743
TI  - Extended access to nicotine leads to a CRF1 receptor dependent increase in
      anxiety-like behavior and hyperalgesia in rats.
AB  - Tobacco dependence is associated with the emergence of negative emotional states
      during withdrawal, including anxiety and nociceptive hypersensitivity. However,
      the current animal models of nicotine dependence have focused on the mechanisms
      that mediate the acute reinforcing effects of nicotine and failed to link
      increased anxiety and pain during abstinence with excessive nicotine self
      administration. Here, we tested the hypothesis that the activation of
      corticotropin-releasing factor-1 (CRF1 ) receptors and emergence of the affective
      and motivational effects of nicotine abstinence only occur in rats with long
      access (>21 hours/day, LgA) and not short (1 hour/day, ShA) access to nicotine
      self-administration. ShA and LgA rats were tested for anxiety-like behavior,
      nociceptive thresholds, somatic signs of withdrawal and nicotine intake after 3
      days of abstinence. The role of CRF1 receptors during abstinence was tested using
      systemic or intracerebral infusion of MPZP (N,N-bis(2-methoxyethyl)-3-(4-methoxy
      2-methylphenyl)-2,5-dimethyl-pyrazolo(1,5alpha)pyrimidin-7-amine), a CRF1
      receptor antagonist, in the central nucleus of the amygdala (CeA). LgA but not
      ShA rats exhibited abstinence-induced increases in anxiety-like behavior and
      nociceptive hypersensitivity, which both predicted subsequent excessive nicotine
      intake and were prevented by systemic administration of MPZP. Intra-CeA MPZP
      infusion prevented abstinence-induced increases in nicotine intake and
      nociceptive hypersensitivity. These findings demonstrate that the model of short
      access to nicotine self-administration has limited validity for tobacco
      dependence, highlight the translational relevance of the model of extended
      intermittent access to nicotine self-administration for tobacco dependence and
      demonstrate that activation of CRF1 receptors is required for the emergence of
      abstinence-induced anxiety-like behavior, hyperalgesia and excessive nicotine
      intake. 

PMID- 23869744
TI  - Follicular dendritic cell-secreted protein is decreased in experimental
      periodontitis concurrently with the increase of interleukin-17 expression and the
      Rankl/Opg mRNA ratio.
AB  - BACKGROUND AND OBJECTIVE: T-helper type 17 (Th17) cells produce interleukin-17
      (IL-17) and help to protect against inflammation and infection in periodontal
      disease. Furthermore, while follicular dendritic cell-secreted protein (FDC-SP)
      may be involved in the inflammation of periodontal tissue, the biological role of
      FDP-SP in periodontal disease is still unknown. The purpose of the present study
      was to clarify the expression of IL-17 and FDC-SP in experimental periodontitis
      in rats. MATERIAL AND METHODS: Seven-week-old male Wistar rats were divided into
      baseline control, sham and test groups. Experimental periodontitis was induced by
      placing a ligature in the mesiopalatal area, and untreated rats served as a
      baseline control group. Morphological changes in alveolar bone were investigated
      7, 14 and 28 d after treatment. Expression of the Rankl, osteoprotegerin (Opg)
      and Il17 genes was analyzed 5 and 7 d after the induction of experimental
      periodontitis. RESULTS: Alveolar bone resorption progressed in the test group for
      7 d, but not thereafter. At 5 d after the induction of periodontitis, the
      Rankl/Opg mRNA ratio and the expression of IL-17 in the test group were
      significantly increased compared with the respective values in the baseline
      control group; however, there were no significant differences between the test
      and control groups at 7 d. The expression of FDC-SP was significantly decreased
      in the test group compared with the baseline control group at 5 and 7 d after the
      induction of periodontitis, and this value had returned to normal levels at 14
      and 28 d. CONCLUSION: These results suggest that both IL-17 and FDC-SP could be
      involved in the inflammatory response, and FDC-SP in the junctional epithelium
      might play an important role in the Th17 cell-related immune response.

PMID- 23869745
TI  - Highly Ag+ selective tripodal gold(I) acetylide-based "off-on" luminescence
      chemosensors based on 3(pipi*) emission switching.
AB  - Newly prepared gold(I) acetylide-based luminescent cation sensors 1c and 1d,
      which bear a novel three-armed flexible conformation, together with control
      molecule 2c, were synthesized in four steps. 1c and 1d exhibit the pi -> pi*
      absorption of the acetylide ligands in fluid solutions and produce the (3)(pipi*)
      emission of the acetylide ligands in the solid state and degassed THF solution.
      The (3)(pipi*) emission of 1c in DMSO can be turned on upon addition of Ag(+).
      The binding ratio between 1c and Ag(+) as well as the binding constant log K were
      determined as 1:1 and 4.35 +/- 0.12 respectively by UV-vis titration experiments.
      The formation of [1c.Ag](+) adduct, which leads to the appearance of new up-field
      peaks, was confirmed by (1)H NMR spectroscopic titrations. The control (1)H NMR
      titration experiments for the acetylide-free analogue 1a and single-armed
      analogue 2c indicate the acetylide groups and tripodal structures are responsible
      for the binding of Ag(+). The control experiment for tripodal gold(I) acetylide
      analogue 1d suggests the change of PPh3 with P(2-Py)Ph2 induces similar binding
      affinity toward Ag(+) but less selectivity toward Ag(+). Free 1c also exhibits
      the anion binding affinity toward F(-), but the Ag(+) adduct [1c.Ag](+) shows
      less affinity toward F(-). 

PMID- 23869746
TI  - The impact of drug discontinuation in patients treated with temporary pacemaker
      due to atrioventricular block.
AB  - INTRODUCTION: Patients treated with a temporary pacemaker (TPM) due to
      atrioventricular (AV) block are often monitored after discontinuation of AV node
      blocking drugs to evaluate the indication for permanent pacing. However, the
      impact of drug discontinuation is sparsely documented. We investigated to what
      extent drug discontinuation abolished the need for permanent pacemaker (PPM)
      implantation. METHODS AND RESULTS: All hospital records of patients who received
      a TPM at Aalborg Hospital, Denmark, between January 2000 and March 2011 (n = 575)
      were retrospectively reviewed. Patients with AV block who were treated with a TPM
      and concomitant cessation of drug therapy were included if there was no other
      underlying mechanism causing the AV block. AV blocking drugs included
      antiarrhythmic agents classes II-IV and digoxin. Fifty-five patients fulfilled
      our inclusion criteria. Forty-seven patients had an indication for a PPM at the
      initial hospital admission, despite drug discontinuation. Of the remaining 8
      patients who were discharged without a PPM, 3 subsequently experienced events: 2
      had recurrence of AV block requiring a PPM, and 1 experienced syncope. Thus, in
      total, 49 (89%) patients had a final indication for a permanent pacemaker (PPM).
      Of patients receiving beta-blocker monotherapy, 26 (96%) had an indication for a
      PPM. TPM implantation was complicated by infection or displacement in 11% of
      cases. CONCLUSIONS: The vast majority of patients treated with a TPM due to AV
      block and who receive beta-blockers alone or in combination with digoxin have a
      final indication for a PPM despite cessation of drug treatment. TPM are
      frequently associated with complications.

PMID- 23869747
TI  - Influence of histological degree of seminiferous tubular degeneration and stage
      of seminiferous cycle on the proliferation of spermatogonia in aged Syrian
      hamster (Mesocricetus auratus).
AB  - The ageing testis is associated with germ loss in the seminiferous epithelium and
      a decrease in spermatogonia proliferation. In this work, we study whether the
      stages of the seminiferous epithelium cycle and/or the degree of histological
      tubular degeneration resulting from ageing is related with this decrease in
      spermatogonia proliferation. Eleven hamsters were used, five aged 6 months and
      six aged 24 months. In both groups, the proliferative activity was studied by
      BrdU immunostaining. The number of BrdU-positive and BrdU-negative cells was
      measured, providing the overall proliferation index in adult and aged testes. The
      mean number of BrdU-positive cells was also determined for each degree of
      histological degeneration of seminiferous epithelium, and a spermatogonia
      proliferation index was obtained for each stage of the seminiferous cycle. Ageing
      caused an overall decrease in the BrdU-positive cell percentage and a decrease in
      the number of BrdU-positive cells in the tubular sections with
      hypospermatogenesis, the sloughing of germ cells and maturation arrest, these
      changes being similar in both young and old animals. The spermatogonia
      proliferation index was only seen to be significantly lower in ageing hamster in
      stages VII-VIII of the seminiferous epithelium cycle. In conclusion, the overall
      decrease in proliferation observed in aged seminiferous epithelium is correlated
      with an increase in the number of degenerated sections of the seminiferous
      tubules, and this decrease is a phenomenon which occurs in specific stages of the
      seminiferous cycle.

PMID- 23869748
TI  - Viewing and making art together: a multi-session art-gallery-based intervention
      for people with dementia and their carers.
AB  - OBJECTIVES: This is the first known study that sought to understand the
      experience of an eight-week art-gallery-based intervention offered at two
      distinctly different galleries for people with mild to moderate dementia and
      their carers. The study examined impact on social inclusion, carer burden, and
      quality of life and daily living activities for a person with dementia. METHOD: A
      mixed-methods pre-post design using standardised questionnaires and interviews
      involved 24 participants (12 with dementia) and compared similar interventions at
      a traditional and a contemporary art gallery. Qualitative data was analysed using
      thematic analysis. RESULTS: No significant pre-post difference was found between
      the traditional or contemporary gallery groups on quantitative measures. There
      was, however, a non-significant trend towards a reduction in carer burden over
      the course of the intervention for both gallery groups. Thematic analysis
      revealed well-being benefits from both traditional and contemporary art gallery
      sites that included positive social impact resulting from feeling more socially
      included, self-reports of enhanced cognitive capacities for people with dementia,
      and an improved quality of life. CONCLUSION: Participants were unanimous in their
      enjoyment and satisfaction with the programme, despite the lack of significance
      from standardised measures. Further consideration of art galleries and museums,
      as non-clinical community resources for dementia care, is warranted. The
      interventions at both galleries helped to foster social inclusion and social
      engagement, enhance the caring relationship between the carers and PWD, support
      the personhood of PWD, and stimulate cognitive processes of attention and
      concentration.

PMID- 23869749
TI  - The application of species criteria in avian taxonomy and its implications for
      the debate over species concepts.
AB  - The debate over species concepts has produced a huge body of literature on how
      species can, may or should be delimited. By contrast, very few studies have
      documented how species taxa are delimited in practice. The aims of the present
      study were to (i) quantify the use of species criteria in taxonomy, (ii) discuss
      its implications for the debate over species concepts and (iii) assess recent
      claims about the impact of different species concepts on taxonomic stability and
      the 'nature' of species. The application of six species criteria was examined in
      taxonomic studies of birds published between 1950 and 2009. Three types of
      taxonomic studies were included: descriptions of new species (N = 329), proposals
      to change the taxonomic rank of species and subspecies (N = 808) and the
      taxonomic recommendations of the American Ornithologists' Union Committee on
      Classification and Nomenclature (N = 176). In all three datasets, diagnosability
      was the most frequently applied criterion, followed by reproductive isolation and
      degree of difference. This result is inconsistent with the popular notion that
      the Biological Species Concept is the dominant species concept in avian taxonomy.
      Since the 1950s, avian species-level taxonomy has become increasingly pluralistic
      and eclectic. This suggests that taxonomists consider different criteria as
      complementary rather than as rival approaches to species delimitation.
      Application of diagnosability more frequently led to the elevation of subspecies
      to species rank than application of reproductive isolation, although the
      difference was small. Hypotheses based on diagnosability and reproductive
      isolation were equally likely to be accepted in a mainstream checklist. These
      findings contradict recent claims that application of the Phylogenetic Species
      Concept causes instability and that broader application of the Biological Species
      Concept can stabilise taxonomy. The criteria diagnosability and monophyly, which
      are commonly associated with Phylogenetic Species Concepts, were used throughout
      the study period. Finally, no support was found for the idea that Phylogenetic
      Species Concepts have caused a change in the 'nature' of species taxa. This study
      demonstrates that there is a discrepancy between widely held perceptions of how
      species are delimited and the way species are actually delimited by taxonomists.
      Theoretically oriented debates over species concepts thus may benefit from
      empirical data on taxonomic practice. 

PMID- 23869750
TI  - A room-temperature catalytic asymmetric synthesis of allenes with ECNU-Phos.
AB  - Three-carbon axial chirality has been asymmetrically established from racemic one
      carbon central chirality efficiently at room temperature: we report here the
      discovery of the first catalytic asymmetric carbonylation of readily available
      racemic propargylic carbonates to access optically active 2,3-allenoates with
      fairly high ee. The combination of [(pi-allyl)PdCl]2 with [(R)-ECNU-Phos], a new
      chiral bisphosphine ligand based on a biphenyl skeleton, demonstrates high
      enantioselectivity. Both enantiomers of allenoates can be obtained at room
      temperature by applying either (R)- or (S)-ECNU-Phos. 

PMID- 23869751
TI  - A metathesis route for BODIPY labeled polyolefins.
AB  - It is demonstrated how acyclic diene metathesis polymerization (ADMET) provides
      an efficient strategy for the labeling of polyolefins. The versatility of
      phosphorus chemistry allows designing substituted BODIPY monomers or chain
      stoppers for the synthesis of precise labeled (degradable) polyphosphoesters. 

PMID- 23869752
TI  - Serial monoxenous transmission of Toxoplasma gondii in cats.
AB  - Abstract :  Oral administration of Toxoplasma gondii oocysts to cats (i.e.,
      monoxenous transmission) typically induces patent infections in fewer than half
      of test subjects. In the present study, oral administration of T. gondii oocysts
      to 5 kittens induced a patent infection in 2 of them, but only 1 kitten shed
      enough oocysts to enable further study. Those monoxenously-produced oocysts were
      administered to another kitten, which produced a second generation of monoxenous
      oocysts, and then those were used to induce a third generation of monoxenous
      oocysts. These results provide a rationale to develop a strain of T. gondii that
      has efficient direct transmission. The isolate of T. gondii that was able to be
      passaged in this manner has been designated the Dubey strain and cultured
      tachyzoites have been donated to a repository. 

PMID- 23869753
TI  - White wine proteins: how does the pH affect their conformation at room
      temperature?
AB  - Our studies focused on the determination of aggregation mechanisms of proteins
      occurring in wine at room temperature. Even if the wine pH range is narrow (2.8
      to 3.7), some proteins are affected by this parameter. At low pH, the formation
      of aggregates and the development of a haze due to proteins sometimes occur. The
      objective of this work was to determine if the pH impacted the conformational
      stability of wine proteins. Different techniques were used: circular dichroism
      and fluorescence spectroscopy to investigate the modification of their secondary
      and tertiary structure and also SAXS to determine their global shape. Four pure
      proteins were used, two considered to be stable (invertase and thaumatin-like
      proteins) and two considered to be unstable (two chitinase isoforms). Two pH
      values were tested to emphasize their behavior (pH 2.5 and 4.0). The present work
      highlighted the fact that the conformational stability of some wine proteins
      (chitinases) was impacted by partial modifications, related to the exposure of
      some hydrophobic sites. These modifications were enough to destabilize the native
      state of the protein. These modifications were not observed on wine proteins
      determined to be stable (invertase and thaumatin-like proteins). 

PMID- 23869754
TI  - Mutational activation of the RocR activator and of a cryptic rocDEF promoter
      bypass loss of the initial steps of proline biosynthesis in Bacillus subtilis.
AB  - The gamma-glutamyl-phosphate reductase (ProA) interlinks both the anabolic and
      osmostress adaptive proline biosynthetic routes of Bacillus subtilis. Because no
      paralogous protein to ProA exists in this microorganism, proA mutants should
      exhibit a tight proline auxotrophic growth phenotype. Contrary to expectations,
      proA mutants formed microcolonies on agar plates lacking proline and faster
      growing Pro(+) suppressor mutants arose. These mutants carried alterations in the
      rocR-rocDEF region encoding enzymes of the arginine degradation pathway and its
      transcriptional activator RocR. They were of two types: (i) mutants carrying
      single amino acid substitutions in RocR resulting in partial inducer-independent
      variants and (ii) mutants carrying single base-pair changes in the vicinity of
      the SigL/Sig-54-dependent -12/-24 class rocDEF promoter that activate a cryptic
      SigA-type promoter. Consequently, enhanced rocDEF transcription should lead to
      increased cellular amounts of the RocD ornithine aminotransferase, an enzyme that
      synthesizes the same reaction product as ProA, gamma-glutamic-semialdehyde/delta
      1-pyrroline-5-carboxylate. This compound can be enzymatically converted into
      proline. The Pro(+) suppressors also exhibited a new regulatory pattern by
      allowing enhanced rocDEF transcription in response to proline availability when
      ammonium is present. Our work provides an example how flexibly bacteria can
      genetically develop routes to bypass constraints imposed on their biosynthetic
      networks and evolve new regulatory mechanisms. 

PMID- 23869755
TI  - Mineral and trace element analysis of saliva from patients with BMS: a cross
      sectional prospective controlled clinical study.
AB  - OBJECTIVE: The aim of this study was to investigate salivary markers related to
      burning mouth syndrome (BMS). STUDY DESIGN: A cross-sectional prospective
      controlled clinical study of 58 patients (28 BMS and 30 control). The presence of
      mineral and trace metals in unstimulated whole saliva was analyzed in BMS
      patients and in control subjects by means of ICP-OES. The parameters analyzed
      were as follows: oral health-related quality of life (OHIP-14) and the Hospital
      Anxiety Depression (HAD) scale. A visual analogue scale (VAS) was used to measure
      the intensity of burning sensation (pain). RESULTS: The mean pain value for
      patients with BMS was 7.8 +/- 2.4. OHIP-14 oral health-related quality of life
      among BMS patients was found to be affected: total BMS OHIP-14 (16.98 +/- 12.29)
      vs. control (8.53 +/- 10.5) with significant difference (P = 0.015).
      Concentrations of the different elements were slightly higher among BMS patients
      but without statistically significant differences for any of the elements
      analyzed (Na, K, Ca, Mg, Fe, Cu, Mn, Zn, B, P, S, Al, Pb, Cd, Cr, Ni, As, Be, Bi,
      Co, Li, Mo, Sb, Se, Sr, Ti, Tl, V). CONCLUSIONS: This study failed to identify
      abnormal levels of minerals or trace elements in saliva of patients with BMS.

PMID- 23869756
TI  - A re-analysis of the long-term effects on life expectancy of the Great Finnish
      Famine of 1866-68.
AB  - The results of studies exploring the long-term consequences of famine during
      foetal or infant development are inconsistent. We tested the hypothesis that
      selection forces occurring during a famine change the distribution of frailty in
      the affected cohorts, possibly hiding negative long-term effects. Using mortality
      data for Finland, gathered from the Human Mortality Database, we explored the
      effect of being born during the Great Finnish Famine of 1866-68 by comparing
      mortality at age 60 and over for the 1850-89 births, taking into account
      unobserved cohort heterogeneity. Contemporaneous Swedish cohorts, unexposed to
      the famine, were used as an additional control group. When cohort heterogeneity
      is accounted for, a lower life expectancy at age 60 for male cohorts in Finland
      born during the famine is observed. The results for females are less conclusive.
      No substantial changes are seen in the Swedish cohorts. In order to provide
      consistent estimates of the long-run effects of famines, selection forces need to
      be considered. 

PMID- 23869757
TI  - Modification of risk, but not survival of esophageal cancer patients by
      esophageal cancer-related gene 1 Arg290Gln polymorphism: a case-control study and
      meta-analysis.
AB  - BACKGROUND AND AIM: Esophageal cancer-related gene 1 (ECRG1) is a novel tumor
      suppressor gene known to affect matrix remodeling, cell growth, and
      differentiation. Previous studies in high incidence geographical regions of
      esophageal cancer (EC) have shown association of ECRG1 Arg290Gln polymorphism
      with risk of esophageal squamous cell carcinoma (ESCC); however, role of this
      variant in low incidence region is missing. So, we aimed to evaluate association
      of ECRG1 Arg290Gln with susceptibility and prognosis of EC patients in low-risk
      north Indian population. METHODS: The genotyping of ECRG1 Arg290Gln polymorphism
      was done in 310 incident EC cases (including 179 follow up cases) and 310 healthy
      controls through polymerase chain reaction-restriction fragment length
      polymorphism. Statistical analysis applied were binary logistic regression for
      risk estimation and Kaplan-Meier/log-rank test for survival analysis. Meta
      analysis of published studies, exploring role of ECRG1 polymorphism in ESCC risk,
      was carried out using MIX 2.0 software. RESULTS: ECRG1 Arg290Gln polymorphism
      significantly conferred 1.8-fold increased risk of EC in dominant model (odds
      ratio = 1.78, 95% confidence interval = 1.27-2.49, P = 0.001). Stratification
      based on clinical phenotypes showed pronounced risk in cases with ESCC
      histopathology and middle/lower third tumor locations. No significant interaction
      with environmental risk factors was observed. Meta-analysis also showed
      significant association of ECRG1 Arg290Gln polymorphism with risk of ESCC. Kaplan
      Meier and Cox regression tests suggested that ECRG1 polymorphism did not modulate
      survival outcome of ESCC patients. CONCLUSIONS: ECRG1 Arg290Gln polymorphism
      significantly affects the susceptibility but not the prognosis of ESCC patients
      in low-risk north Indian population.

PMID- 23869758
TI  - Interleukin-6-induced satellite cell proliferation is regulated by induction of
      the JAK2/STAT3 signalling pathway through cyclin D1 targeting.
AB  - OBJECTIVES: To determine whether interleukin-6 (IL-6) stimulates rat muscle
      satellite cell proliferation in culture, and if so, to clarify the signalling
      mechanisms. MATERIALS AND METHODS: Primary satellite cells were isolated from
      thirty male F344 rats, 11 weeks of age. IL-6 at concentrations of 0.01, 0.1, 1,
      10 or 100 ng/ml was added to culture media. RESULTS: IL-6 at 0.01-1 ng/ml induced
      dose-dependent increase in cell proliferation. After treatment with 1 ng/ml IL-6,
      cell proliferation increased by 31%, and p-STAT3(+) /MyoD(+) cells increased in
      number compared to those in control media (P < 0.05). Inhibitors of JAK2 (AG 490)
      and STAT3 (STAT3 peptide) blocked the increase in BrdUrd(+) cell numbers at 6 h
      post stimulation with 1 ng/ml IL-6 (P < 0.05). Furthermore, cyclin D1 mRNA
      expression and cyclin D1(+) /MyoD(+) cell numbers significantly increased in
      cultures treated with 1 ng/ml IL-6 compared to those in control media (P < 0.05).
      In contrast, treatment with 10 and 100 ng/ml IL-6 did not stimulate cell
      proliferation. Treatment with 10 ng/ml IL-6 induced greater SOCS3 mRNA expression
      than with 1 ng/ml IL-6 and control media. Moreover, co-localization of SOCS3 and
      myogenin was observed after treatment with 10 ng/ml IL-6. CONCLUSIONS: IL-6
      induced dose-dependent increase in satellite cell proliferation by activating the
      JAK2/STAT3/cyclin D1 pathway.

PMID- 23869759
TI  - TNFalpha-activated stromal COX-2 signalling promotes proliferative and invasive
      potential of colon cancer epithelial cells.
AB  - OBJECTIVES: Up to now it has been unclear whether stromal/epithelial interaction
      affects progression of colon cancer. This study was designed to examine effects
      of tumour necrosis factor alpha (TNFalpha)-activated stromal cyclooxygenase-2
      (COX-2) signalling on proliferation and invasiveness of colon cancer epithelial
      cells. MATERIALS AND METHODS: Cyclooxygenase-2 mRNA and protein were determined
      by real-time PCR and western blotting and prostaglandin E2 (PGE2 ) was assayed by
      radioimmunoassay. Cell proliferation and invasiveness were determined by
      transwell chamber assays and protein kinase C (PKC) was assayed by Biotrak(TM)
      PKC Assay System. RESULTS: Our results indicated that TNFalpha, a powerful
      inflammatory cytokine, strongly promoted COX-2 expression and PGE2 production in
      colon cancer-associated fibroblasts. Using in vitro assays for estimating
      proliferative and invasive potential, we discovered that activation of stromal
      COX-2 signalling significantly promoted proliferation and invasiveness of colon
      cancer epithelial cells. In addition, selective COX-2 inhibitor N-[2
      (Cyclohexyloxy)-4-nitrophenyl]methanesulfonamide, blocked such proliferative and
      invasive effects on the cancer epithelial cells. In this process, PKC was
      involved in activation of COX-2 signalling in the fibroblasts. CONCLUSION: We
      conclude that activation of stromal COX-2 signalling by TNFalpha played a major
      role in promoting proliferation and invasiveness of colon cancer epithelial
      cells.

PMID- 23869760
TI  - 5-aminolaevulinic acid/photo-dynamic therapy and gefitinib in non-small cell lung
      cancer cell lines: a potential strategy to improve gefitinib therapeutic
      efficacy.
AB  - OBJECTIVES: Often, non-small cell lung cancers (NSCLC) respond only poorly to the
      tyrosine kinase inhibitor (TKI) gefitinib, which targets the epidermal growth
      factor receptor (EGFR), these poor responders EGFRs lacking activating mutations.
      In this study, we have attempted to improve TKI response of NSCLC cell lines
      (A549 and H1299) devoid of EGFR mutations, by combination of gefitinib and 5
      ALA/photodynamic therapy (PDT). MATERIALS AND METHODS: Cells of the two lines
      were incubated with gefitinib (from 0.5 to 50 mm, for 48 h) then irradiated at
      doses ranging from 4 to 20 J/cm(2) ; 5-ALA concentration and incubation time were
      kept constant (1 mm for 3 h). We analysed cell viability, colony-forming
      efficiency, cell cycle parameters, proteasome and NF-kappaB activity and
      expression patterns of specific proteins, after individual or combined
      treatments. RESULTS: Effects (antagonistic, additive or synergistic) of
      combination treatment were evaluated using a predictive model (combination index)
      for expected interactive effects and results are consistent with mutual
      potentiation exceeding simple additivity. Investigation of molecular mechanisms
      underlying cytotoxic effects indicated that combination treatment impaired
      proteasome function, inhibited NF-kappaB transcriptional activity and hampered
      AKT pro-survival signalling. CONCLUSIONS: The results of this study show that
      poor response of cells devoid of EGFR activating mutations to TKIs, can be
      overcome by combining gefitinib with 5-ALA/photodynamic therapy (PDT).

PMID- 23869761
TI  - FGF-2 addition during expansion of human bone marrow-derived stromal cells alters
      MSC surface marker distribution and chondrogenic differentiation potential.
AB  - OBJECTIVES: Although clinical applications using mesenchymal stromal cells (MSCs)
      are becoming more frequent, procedures for their in vitro culture are far from
      standardized. Growth factors such as FGF-2 are frequently added during expansion
      to improve population growth and differentiation characteristics. However, up to
      now its influence on surface marker distribution of MSCs has been close to
      unknown. The purpose of this study was therefore to analyse effects of FGF-2
      supplementation on pre-selection of MSC subpopulations. MATERIALS AND METHODS:
      Mesenchymal stromal cells were harvested from bone marrow of six patients and
      expanded in alpha-MEM or DMEM-LG. Starting in passage 2, 10 ng/ml FGF-2 was
      administered and non-supplemented media were used as controls. Growth indices
      were calculated from P0 to P4. After P4, fluorescence cytometry for common MSC
      surface markers was performed and standard chondrogenic, adipogenic and
      osteogenic differentiation protocols were applied. RESULTS: Cell population
      growth indices were higher for those in FGF-2 supplemented media. Significant
      differences in surface marker distribution were observed for CD13, CD14, CD49,
      CD90, CD340 and STRO-1 depending on respective culture conditions. FGF-2
      suppressed CD146 expression in both alpha-MEM and DMEM-LG. No differences in
      adipogenic and osteogenic differentiation potential could be observed, while FGF
      2 significantly improved chondrogenic differentiation in DMEM-LG. CONCLUSIONS:
      While holding the benefit of improving MSC chondrogenic differentiation
      potential, FGF-2 pre-selects certain MSC subtypes. Our data clearly show that
      expansion culture conditions have a significant effect on distribution of a
      number of MSC surface markers.

PMID- 23869762
TI  - Effects of human epidermal growth factor gene-transfected mesenchymal stem cells
      on fibroblast migration and proliferation.
AB  - OBJECTIVES: We were interested in determining whether epidermal growth factor
      gene-transfected mesenchymal stem cells (EGF-MSC) would accelerate fibroblast
      migration and proliferation. MATERIALS AND METHODS: Fibroblasts were cultured in
      serum-free conditioned media from EGF-MSC; RT-PCR was performed to detect
      expression of EGF gene in EGF-MSCs. EGF protein levels in cell culture
      supernatants from EGF-MSC were assayed by ELISA and proliferation of EGF-MSC
      treated fibroblasts was performed using MTT assay. Effects of EGF-MSC on
      fibroblast migration were evaluated using scratch wound and transmigration
      assays. Cell adhesion molecules, cell dynamics molecules and phospho-(Ser) kinase
      substrate expressions of EGF-MSC-treated fibroblasts were evaluated by western
      blotting. RESULTS: EGF gene expression increased in EGF-MSCs and viability of EGF
      MSC-treated fibroblasts was elevated. EGF-MSC-treated fibroblasts showed
      increased migration compared to controls. Expressions of cell adhesion molecules
      (beta-catenin, N-cadherin), cell dynamics molecules (cofilin, ezrin) and phospho
      (Ser) kinase substrates (phospho-MAPK/CDK substrate, phospho-Arg-(Ser)-X-Tyr/Phe
      X-pSer motif) increased in EGF-MSC-treated fibroblasts. These results imply that
      EGF-MSCs contributed to enhancing the wound healing process by increased cell
      adhesion, dynamic effects, fibroblast migration, and proliferation. CONCLUSIONS:
      This study indicates that EGF-MSCs had a positive influence on fibroblast
      migration and proliferation and EGF-MSC may provide a useful strategy for wound
      healing.

PMID- 23869763
TI  - Effects of bone morphogenetic protein-4 (BMP-4) on adipocyte differentiation from
      mouse adipose-derived stem cells.
AB  - OBJECTIVES: As mesenchymal stem cells (MSCs) can be isolated easily from adipose
      tissues while retaining their self-renewal and multi-potential differentiation
      capacities, they hold promising possibilities for being applied extensively in
      tissue engineering. Bone morphogenetic protein (BMP) family members have been
      reported to provide instructive signals to MSCs for them to differentiate into
      several different cell lineages. The study described here aims to investigate
      whether BMP-4 could promote adipose-derived stem cell (ASC) differentiation into
      adipocytes under various concentrations. MATERIALS AND METHODS: ASCs were
      isolated from mouse inguinal adipose pads and cultured in vitro. 10 ng/ml and 50
      ng/ml BMP-4 were added to adipogenic media for 8 days. Oil red-O staining,
      reverse transcription/polymerase chain reaction and immunocytofluorescence
      staining were performed to examine differentiation of the ASCs. RESULTS: As
      indicated by increased expression of adipogenic and lipogenic genes (PPAR-gamma,
      APN and LPL) and proteins, 50 ng/ml BMP-4 seemed to induce mASCs to differentiate
      into the adipo-lineage compared to 10 ng/ml BMP-4, and control groups. In
      addition, lipid droplets accumulated within the adipocytes under 50 ng/ml BMP-4
      stimulation, as shown by oil red-O staining. CONCLUSIONS: Our present study
      suggests that BMP-4, as an adipo-inducing factor, promoted adipogenesis of ASCs
      at higher concentrations (50 ng/ml) and can perhaps be considered as a candidate
      for use in adipose tissue engineering.

PMID- 23869764
TI  - KLF5 strengthens drug resistance of ovarian cancer stem-like cells by regulating
      survivin expression.
AB  - OBJECTIVES: Ovarian cancer stem-like cells (CSCs), which can form non-adherent
      sphere cells in a stem-cell selection culture system, exhibit stemness and drug
      resistance to chemotherapeutics, which are properties not observed in
      differentiated cells. Recent studies have demonstrated that Kruppel-like factor 5
      (KLF5) is involved in cell proliferation and mediates cell survival and
      tumourigenesis. Here, we investigated the role of KLF5 and its downstream target
      survivin, in strengthening drug resistance of ovarian CSCs. MATERIALS AND
      METHODS: Ovarian cancer cell line SKOV3 was cultured under serum-free conditions
      and differentiating conditions to promote formation of sphere cells and
      differentiated cells, respectively. siRNA-KLF5 was used to knock down KLF5, and
      survivin expression vector was used to overexpress survivin. Cells were further
      analysed by qPCR, immunofluorescence staining and western blotting. Chromatin
      immunoprecipitation (ChIP) assay and electrophoretic mobility shift assay (EMSA)
      were performed to investigate the relationship between KLF5 and survivin
      expression. Drug resistance was examined by MTT and apoptosis assays. RESULTS:
      KLF5 was highly expressed in the ovarian cancer cell line SKOV3 sphere cells,
      accompanied by elevated survivin expression. Silencing KLF5 by small interfering
      RNA in sphere cells down-regulated survivin expression, which also sensitized the
      sphere cells to apoptosis induced by chemotherapeutic drugs (cisplatin or
      paclitaxel). Furthermore, ChIP assay, survivin overexpression and EMSA results
      indicated that KLF5 controlled survivin expression by directly binding the
      surivin promoter in the cells. CONCLUSIONS: The KLF5-mediated signalling pathway
      is a potential target for elimination of ovarian CSCs.

PMID- 23869765
TI  - Enrichment of ovarian cancer stem-like cells is associated with epithelial to
      mesenchymal transition through an miRNA-activated AKT pathway.
AB  - OBJECTIVES: Evidence has indicated that ovarian epithelial cancer-type cells
      under serum-free culture conditions can form spheroid cells and exhibit
      characteristics expected of cancer stem-like cells (CSCs). However, the mechanism
      by which differentiated ovarian cancer cells acquire stem-cell properties during
      CSC enrichment has needed to be elucidated. Recent studies have demonstrated that
      induction of epithelial to mesenchymal transition (EMT) can generate CSCs and be
      associated with tumour aggressiveness and metastasis. MATERIALS AND METHODS:
      Ovarian epithelial cancer cell lines, SKOV3 and HO8920, were cultured for
      spheroid cells and adherent cells. CSC enrichment was investigated using MTT
      assay, flow cytometery and qRT-PCR and expression level of PI3K/AKT pathway
      components was analysed by western blotting. RESULTS: Compared to adherent cells,
      the spheroid cells expressed mesenchymal markers highly and exhibited
      significantly more motility; we also observed increases in phosphate AKT1 levels
      in the spheroid cells. Moreover, transfection of miR-20a or miR-200c led to
      corresponding reduction in endogenous PTEN protein, while AKT1 and phosphate AKT1
      levels were upregulated in miRNAs-transfected cells. Finally, PI3K/AKT pathway
      inhibitor LY294002 reduced expressions of mesenchymal markers and stem-cell gene
      activity in spheroid cells, enhancing sensitivity of spheroid cells to paclitaxel
      treatment. CONCLUSIONS: Our findings demonstrate that EMT contributed to
      enrichment of ovarian CSCs in vitro, making EMT targeting in epithelial ovarian
      cancer a novel therapeutic option.

PMID- 23869766
TI  - Promyelocytic leukaemia zinc finger maintains self-renewal of male germline stem
      cells (mGSCs) and its expression pattern in dairy goat testis.
AB  - OBJECTIVES: Previous studies have shown that promyelocytic leukaemia zinc finger
      (PLZF) is a spermatogonia-specific transcription factor in the testis, required
      to regulate self-renewal and maintenance of the spermatogonia stem cell. Up to
      now, expression and function of PLZF in the goat testis has not been known. The
      objectives of this study were to investigate PLZF expression pattern in the dairy
      goat and its effect on male goat germline stem cell (mGSC) self-renewal and
      differentiation. MATERIALS AND METHODS: Testis development and expression
      patterns of PLZF in the dairy goat were analysed by haematoxylin and eosin
      staining, immunohistochemistry and reverse transcription-polymerase chain
      reaction (RT-PCR). Furthermore, effects of PLZF overexpression on mGSC self
      renewal and differentiation were evaluated by quantitative RT-PCR (QRT-PCR),
      immunofluorescence and BrdU incorporation assay. RESULTS: Promyelocytic leukaemia
      zinc finger was essential for dairy goat testis development and expression of
      several proliferation and pluripotency-associated proteins including OCT4, C-MYC
      were upregulated by PLZF overexpression. The study demonstrated that PLZF played
      a key role in maintaining self-renewal of mGSCs and its overexpression enhanced
      expression of proliferation-associated genes. CONCLUSIONS: Promyelocytic
      leukaemia zinc finger could function in the dairy goat as well as in other
      species in maintaining self-renewal of germline stem cells and this study
      provides a model to study the mechanism on self-renewal and differentiation of
      mGSCs in livestock.

PMID- 23869767
TI  - Oxygen consumption in T-47D cells immobilized in alginate.
AB  - OBJECTIVES: Encapsulation or entrapment of cells is increasingly being used in a
      wide variety of scientific studies for tissue engineering and development of
      novel medical devices. The effect on cell metabolism of such systems is, in
      general, not well characterized. In this work, a simple system for monitoring
      respiration of cells embedded in 3-D alginate cultures was characterized.
      MATERIALS AND METHODS: T-47D cells were cultured in alginate gels. Oxygen
      concentration curves were recorded within cell-gel constructs using two different
      sensor systems, and cell viability and metabolic state were characterized using
      confocal microscopy and commercially available stains. RESULTS: At sufficient
      depth within constructs, recorded oxygen concentration curves were not
      significantly influenced by influx of oxygen through cell-gel layers and oxygen
      consumption rate could be calculated simply by dividing oxygen loss in the system
      per time, by the number of cells. This conclusion was supported by a 3-D numeric
      simulation. For the T-47D cells, the oxygen consumption rate was found to be 61
      +/- 6 fmol/cell/h, 3-4 times less than has previously been found for these cells,
      when grown exponentially in monolayer culture. CONCLUSIONS: The experimental set
      up presented here may be varied in multiple ways by changing the cell-gel
      construct 3-D microenvironment, easily allowing investigation of a variety of
      factors on cell respiration.

PMID- 23869769
TI  - Isolation and characterization of novel S-equol-producing bacteria from brines of
      stinky tofu, a traditional fermented soy food in Taiwan.
AB  - Six strains capable of transforming daidzein to S-equol were isolated from the
      fermented brines of stinky tofu purchased in Taiwan. Daidzein was completely
      converted into S-equol within 24h of incubation in five strains. All the strains
      were gram-positive, rod-shaped, obligately anaerobic, non-motile, and non-spore
      forming. In a phylogenetic analysis based on 16S rRNA gene sequences, the strains
      distributed into three groups in the family Coriobacteriaceae. SNR40-432 (Group
      I) showed 98.6% 16S rRNA gene similarity and 48-49% DNA-DNA relatedness with
      Paraeggerthella hongkongensis HKU10(T), suggesting the possibility that SNR40-432
      represents a new species in the genus Paraeggerthella. SNR48-44 (Group II) and
      SNR44-10, SNR45-571, SNR46-41, SNR48-350 (Group III) showed a maximum of 92.2 and
      92.1% 16S rRNA gene similarities with Eggerthella sinensis HKU14(T) and
      Eggerthella lenta JCM9979(T), respectively, which denotes that each group may
      represent a novel genus and species in the family Coriobacteriaceae. This is the
      first report isolating equol-producing bacteria from food.

PMID- 23869771
TI  - The baby and infant screen for children with autism traits-part 2: The
      development of age-based cutoffs.
AB  - OBJECTIVE: To create age-based scoring procedures for the BISCUIT-Part 2, an
      assessment measure of comorbid psychopathology in infants and toddlers aged 17-37
      months. METHOD: The standard deviation from the mean method was used to develop
      separate age-based cutoffs for those with an autism spectrum disorder (ASD) and
      those with non-ASD related developmental delays, using a sample of 2867 infants
      and toddlers and their parents. RESULTS: As age increased in those with ASD,
      higher cutoff scores were indicated. Less variation was seen in the cutoff scores
      established for those with non-ASD related delays. CONCLUSION: The findings
      suggest that as children with ASD grow older, symptoms of comorbidity become more
      prevalent and easier to detect. The implications of these results, as well as
      possible areas of future research, are discussed.

PMID- 23869772
TI  - Nd(3+)-sensitized upconversion nanophosphors: efficient in vivo bioimaging probes
      with minimized heating effect.
AB  - Upconversion (UC) process in lanthanide-doped nanomaterials has attracted great
      research interest for its extensive biological applications in vitro and in vivo,
      benefiting from the high tissue penetration depth of near-infrared excitation
      light and low autofluorescence background. However, the 980 nm laser, typically
      used to trigger the Yb(3+)-sensitized UC process, is strongly absorbed by water
      in biological structures and could cause severe overheating effect. In this
      article, we report the extension of the UC excitation spectrum to shorter
      wavelengths, where water has lower absorption. This is realized by further
      introducing Nd(3+) as the sensitizer and by building a core/shell structure to
      ensure successive Nd(3+) -> Yb(3+) -> activator energy transfer. The efficacy of
      this Nd(3+)-sensitized UC process is demonstrated in in vivo imaging, and the
      results confirmed that the laser-induced local overheating effect is greatly
      minimized.

PMID- 23869773
TI  - Nanoadsorbents: classification, preparation, and applications (with emphasis on
      aqueous media).

PMID- 23869774
TI  - Benzothiazoles: how relevant in cancer drug design strategy?
AB  - Heterocyclic compounds, analogs and derivatives have attracted attention due to
      their diverse biological and pharmacological properties. Benzoheterocycles such
      as benzothiazoles, benzimidazoles and benzoxazoles are constituents of many
      bioactive heterocyclic compounds, having wider range of applications. They have
      been extensively studied for their biological activities, and can serve as unique
      and versatile scaffolds for drug design. The benzothiazole, in the family of
      heterocyclic compounds has assumed special significance in synthetic chemistry,
      pharmaceutical chemistry as well as in clinical applications because of its anti
      tumor properties. This review is organized in the following ways. It begins with
      brief introduction on the chemical diversity of synthetic analogs of
      benzothiazole. After this, drug design strategy and mechanisms of action through
      its diverse biological targets in which benzothiazole and its derivatives display
      their anticancer activity are discussed. It ends with the metabolism pattern of
      benzothiazole and its analogs. Analysis of the structure-activity relationships
      (SAR), quantitative structure-activity relationships (QSAR) as well as on docking
      studies of this family of compounds highlights the potential that may lead to the
      development of novel anticancer agents. Such relationships will definitely create
      lot of interest among the researchers to synthesize optimized variety of
      benzothiazole derivatives and to screen them for their anticancer activity. 

PMID- 23869775
TI  - Orai1 and transient receptor potential channels as novel molecular targets to
      impair tumor neovascularization in renal cell carcinoma and other malignancies.
AB  - The term "angiogenic switch" describes one of the earlier events of
      tumorigenesis, that occurs when the balance between pro-and anti-angiogenic
      factors shifts towards a pro-angiogenic outcome. This leads to the transition
      from a microscopic indolent lesion to a macroscopic and vascularised primary
      tumor, that may eventually metastasize and spread to distant sites. The molecular
      mechanisms underlying such a critical step in the carcinogenetic process have
      been extensively investigated. Both local endothelial cells (ECs) and endothelial
      progenitor cells (EPCs), recruited from bone marrow, have been implicated in the
      angiogenic switch, which is ultimately triggered by a plethora of growth factors
      released by cancer cells, pivotal among which is vascular endothelial growth
      factor (VEGF); indeed, VEGF both activates ECs nearby the growing tumor, and
      leads to EPC mobilization into the circulation. In kidney, in particular, the
      frequent mutation of the Von Hippel Lindau tumor suppressor gene leads to an
      overproduction of pro-angiogenic factors which makes this neoplasm quite
      sensitive to antiangiogenic drugs. However, it is now evident that the use of
      VEGF(Rs) inhibitors in everyday clinical practice is not as effective as observed
      in murine models. The investigation of alternative signaling pathways involved in
      the angiogenic switch is, therefore, imperative in order to induce tumor
      regression whereby preventing harmful drawback consequences. Ca(2+) entry across
      the plasma membrane has long been known to stimulate mature ECs to undergo
      angiogenesis. Recent work from several groups worldwide has then outlined that
      members of the Transient Receptor Potential (TRP) super-family of cationic
      channels and Orai1 provide the pathway for such proangiogenic Ca(2+) signal. In
      addition, Canonical TRP 1 (TRPC1) and Orai1 channels control proliferation and
      tubulogenesis in both normal EPCs and EPCs isolated from peripheral blood of
      tumor patients. As a consequence, TRP channels and Orai1 might serve as novel
      molecular targets to develop alternative and more effective strategies of
      angiogenesis inhibition.

PMID- 23869776
TI  - Electrochemical study of ellipticine interaction with single and double stranded
      oligonucleotides.
AB  - Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is an alkaloid that has
      been isolated from plants of an Apocynaceae family. It is one of the simplest
      naturally occurring alkaloids with a planar structure. Over the past decades,
      ellipticine became a very promising antitumor agent. Interaction with DNA is one
      of the most studied ellipticine effects on cell division. This phenomenon is not
      clearly explained so far. In our experiments we studied interaction of
      ellipticine with single-stranded and double-stranded oligonucleotides by
      electrochemical methods on mercury electrode. Differential pulse voltammetry was
      applied for ellipticine (Elli) and CA peak detection. Square wave voltammetry was
      applied for G peak detection. The effect of the interaction time and ellipticine
      concentrations on interactions of ellipticine with single- and double-stranded
      oligonucleotides was tested too.

PMID- 23869777
TI  - Recent advances in small molecule prodrugs for cancer therapy.
AB  - Chemotherapy has been performed to treat metastatic cancers but with varying
      degrees of success. The optimal potential of chemotherapy has not been achieved
      yet. Numerous compounds cannot be further developed to produce potent drugs
      because these compounds exhibit poor druggability. To resolve this issue,
      researchers developed prodrugs in drug discovery because these drugs can be
      efficiently used. Many small-molecule prodrugs have been designed and synthesized
      as anticancer agents for several years, and great progress has been achieved. In
      this study, recently developed, efficient anticancer prodrugs were reviewed,
      particularly small molecule prodrugs. Moreover, small molecule anticancer
      prodrugs were summarized according to different types of chemical structures and
      properties.

PMID- 23869778
TI  - Implication of CYP24A1 splicing in breast cancer.
AB  - The expression of CYP27B1 or vitamin D 1alpha-hydroxylase (1alpha-OHase) and
      CYP24A1 in specific tissues may act as the central part between 25-hydroxyvitamin
      D [25(OH)D] serum levels and the anticancer effects of1alpha,25-dihydroxyvitamin
      D [1alpha,25(OH)2D3],alternative splicing of these enzymes may affect their
      biological functions. Here, we describe the expression of CYP24A1 and its
      splicing variants detected in breast cells and tissues. Manifestation of CYP24A1
      mRNA was measured by RT-PCR followed by western blot analysis for protein
      expression. In MCF-7 cells, the expression of CYP24A1 protein was reduced by
      about 57% compared to MCF-10F cells. Western blot analysis revealed a signal band
      at 56 kDa, with additional bands detected at 42 and 44 kDa. The expression of
      CYP24A1 mRNA was reduced by about 58% in breast cancer tissues. We found only one
      signal in the benign tissues at 56 kDa in western blot, whereas in malignant
      tissue, an additional band was detected at 40kDa. Our results suggest that
      alternative splicing of CYP24A1 may lead to a catalytically dysfunctional enzyme.

PMID- 23869780
TI  - Effects of limonoid cedrelone on MDA-MB-231 breast tumor cells in vitro.
AB  - Cancer is the second leading cause of death, preceded only by cardiovascular
      diseases, and there is epidemiological evidence that demonstrate this tendency is
      emerging worldwide. Brazil has an extensive vegetal biodiversity with more than
      55,000 species listed. Such biodiversity collaborates with the finding of
      compounds which could be the basis for the design of new anti-tumor drugs, with
      fewer side effects than the conventional chemotherapy used currently. Cedrelone
      is a limonoid isolated from Trichilia catigua (Meliaceae) which is a native
      Brazilian plant. This study demonstrates that cedrelone inhibits proliferation,
      adhesion, migration and invasion of breast tumor cells from the line MDA-MB-231.
      The effects of cell migration and invasion on MDA-MB-231 cell may be explained,
      at least in part, by the ability of cedrelone to inhibit MMP activity. We also
      demonstrate that cedrelone is able to induce apoptosis in MDA-MB-231 cells. There
      are only a few works investigating the effect of limonoids in cellular processes
      closely related to tumor progression such as adhesion, migration and invasion. To
      the best of our knowledge, this is the first work describing the effects of a
      limonoid on tumor and non-tumor cell adhesion process. 

PMID- 23869779
TI  - Adenoviral vectors for prodrug activation-based gene therapy for cancer.
AB  - Cancer cell heterogeneity is a common feature - both between patients diagnosed
      with the same cancer and within an individual patient's tumor - and leads to
      widely different response rates to cancer therapies and the potential for the
      emergence of drug resistance. Diverse therapeutic approaches have been developed
      to combat the complexity of cancer, including individual treatment modalities
      designed to target tumor heterogeneity. This review discusses adenoviral vectors
      and how they can be modified to replicate in a cancer-specific manner and deliver
      therapeutic genes under multi-tiered regulation to target tumor heterogeneity,
      including heterogeneity associated with cancer stem cell-like subpopulations.
      Strategies that allow for combination of prodrug-activation gene therapy with a
      novel replication-conditional, heterogeneous tumor-targeting adenovirus are
      discussed, as are the benefits of using adenoviral vectors as tumor-targeting
      oncolytic vectors. While the anticancer activity of many adenoviral vectors has
      been well established in preclinical studies, only limited successes have been
      achieved in the clinic, indicating a need for further improvements in activity,
      specificity, tumor cell delivery and avoidance of immunogenicity. 

PMID- 23869781
TI  - CYP24A1 as a potential target for cancer therapy.
AB  - Increasing evidence has accumulated to suggest that vitamin D may reduce the risk
      of cancer through its biologically active metabolite, 1alpha,25(OH)2D3, which
      inhibits proliferation and angiogenesis, induces differentiation and apoptosis,
      and regulates many other cellular functions. Thus, it is plausible to assume that
      rapid clearance of 1alpha,25(OH)2D3 by highly expressed CYP24A1 could interrupt
      the normal physiology of cells and might be one cause of cancer initiation and
      progression. In fact, enhancement of CYP24A1 expression has been reported in
      literature for many cancers. Based on these findings, CYP24A1-specific inhibitors
      and vitamin D analogs which are resistant to CYP24A1-dependent catabolism might
      be useful for cancer treatment. CYP24A1-specific inhibitor VID400, which is an
      azole compound, markedly enhanced and prolonged the antiproliferative activity of
      1alpha,25(OH)2D3 in the human keratinocytes. Likewise, CYP24A1-resistant analogs
      such as 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)2D3 (O2C3) and its C2-epimer ED-71
      (Eldecalcitol), and 19nor- 2alpha-(3-hydroxypropyl)-1alpha,25(OH)2D3 (MART-10)
      showed potent biological effects. Our in vivo studies using rats revealed that
      MART-10 had a low calcemic effect, which is a suitable property as an anticancer
      drug. Much lower affinity of MART-10 for vitamin D binding protein (DBP) as
      compared with 1alpha,25(OH)2D3 may be related to its more potent cellular
      activities. Based on these results, we conclude that (1) high affinity for VDR,
      (2) resistance to CYP24A1-dependent catabolism, (3) low affinity for DBP, and (4)
      low calcemic effect may be required for designing potent vitamin D analogs for
      cancer treatment. 

PMID- 23869783
TI  - Recent advances in multinuclear complexes as potential anticancer and DNA binding
      agents.
AB  - In the search for new metal-based anticancer agents as effective candidates for
      cisplatin, a lot of strategies such as synthesis of cisplatin analogs, trans
      platinum compounds and non-platinum metal complexes have been put forward in the
      last forty years. The concept of multinuclearity for improving the
      chemotherapeutic activity has been proven in multinuclear platinum complexes such
      as BBR3464, recently, the effective approach has been successfully transferred to
      ruthenium complexes. In this review, we highlighted the recent progress in
      multinuclear platinum complexes and ruthenium complexes as anticancer agents, and
      their novel DNA binding properties such as phosphate clamps, long range DNA cross
      links, bisintercalation, interduplex cross links and DNA-protein cross-links were
      summarized to shed light on the rational design of polynuclear complexes as
      anticancer agents. 

PMID- 23869784
TI  - Cytochrome p450 for cancer prevention and therapy.

PMID- 23869785
TI  - Nonsteroidal aromatase inhibitors for the treatment of breast cancer: an update.
AB  - Estrogens are known to be important in breast cancer growth in both pre- and post
      menopausal women. Although circulating estrogen concentrations are very low after
      menopause, peripheral tissues generate sufficient concentrations to stimulate
      tumor growth. As aromatase is the rate-limiting enzyme in estrogen biosynthesis,
      inhibitors of this enzyme represent effective targeted therapy for breast cancer.
      Three compounds are now FDA approved and have become the first-choice endocrine
      drugs for postmenopausal breast cancer patients, since they are associated with
      superior activity and better general tolerability when compared with the estrogen
      receptor modulator tamoxifen. Nevertheless, some questions concerning the use of
      aromatase inhibitors for the treatment of breast cancer still need to be
      addressed, mainly related to their side-effects and the development of
      resistance, making research in this field still appealing. Many research groups,
      including our own, are still dealing with the search of new compounds that
      possess aromatase inhibitory properties. In this review an update of the latest
      achievements in the field of nonsteroidal aromatase inhibitors will be given. 

PMID- 23869786
TI  - Response of neotropical bat assemblages to human land use.
AB  - Neotropical bats are sensitive to human-induced habitat changes, and some authors
      believe bats can be used as bioindicators. In the literature, however, the
      results are disparate. Some results show bat diversity deceases as disturbance
      increases, whereas others indicate no effect. Determining the general response
      patterns of bats when they encounter different degrees of human-induced
      disturbance across the Neotropics would help to determine their usefulness as
      bioindicators. In a series of meta-analyses, we compared the occurrence frequency
      of bat species between well-preserved forests and human-use areas. We obtained
      data through an extensive review of published peer-reviewed articles, theses, and
      reports. The overall effect size indicated that human-use areas harbored more bat
      species than well-preserved forests. Different response patterns emerged when
      meta-analyses were conducted separately by family, feeding habit, vegetation
      stratum, and conservation status. Our results suggest that bat assemblages
      display strong responses to forest loss and land-use change and that the
      direction and magnitude of these responses depends on the bat group under study
      and the type of disturbance. Our results are consistent with the idea that bats
      are useful for assessing the effects of habitat changes in the Neotropics.
      However, with our meta-analyses we could not detect fine differences in bat
      feeding habits, especially within Phyllostomidae, or elucidate the effect of
      landscape configuration.

PMID- 23869787
TI  - Oral delivery of therapeutic proteins and peptides: a review on recent
      developments.
AB  - Advent of recombinant technology in protein synthesis has given birth to a new
      range of biopharmaceuticals. These therapeutic peptides and proteins are now
      emerging as an imperative part of various treatment protocols especially in the
      cancer therapeutics. Despite extensive research efforts, oral delivery of
      therapeutic peptide or protein is still a challenge for pharmaceutical industries
      and researchers. Number of factors including high proteolytic activity and low pH
      conditions of gastrointestinal tract act as major barriers in the successful
      delivery of intact protein/peptide to the targeted site. Low permeability of
      protein/peptide across the intestinal barrier is also a factor adding to the low
      bioavailability. Therefore, because of the short circulatory half-life exhibited
      by peptides in vivo, they need to be administered frequently resulting in
      increased cost of treatment and low patient compliance. Nano-carrier-based
      delivery presents an appropriate choice of drug carriers owing to their property
      to protect proteins from degradation by the low pH conditions in stomach or by
      the proteolytic enzymes in the gastrointestinal tract. This review focuses on
      recent aspects and patents on oral delivery of therapeutic proteins and peptides
      with special emphasis on nano-carrier-based approach.

PMID- 23869782
TI  - Cytochromes p450 and skin cancer: role of local endocrine pathways.
AB  - Skin is the largest body organ forming a metabolically active barrier between
      external and internal environments. The metabolic barrier is composed of
      cytochromes P450 (CYPs) that regulate its homeostasis through activation or
      inactivation of biologically relevant molecules. In this review we focus our
      attention on local steroidogenic and secosteroidogenic systems in relation to
      skin cancer, e.g., prevention, attenuation of tumor progression and therapy. The
      local steroidogenic system is composed of locally expressed CYPs involved in
      local production of androgens, estrogens, gluco- and mineralo-corticosteroids
      from cholesterol (initiated by CYP11A1) or from steroid precursors delivered to
      the skin, and of their metabolism and/or inactivation. Cutaneous 7-hydroxylases
      (CYP7A1, CYP7B1 and CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols
      with modifying effects on local tumorigenesis. CYP11A1 also transforms 7
      dehydrocholesterol (7DHC)->22(OH)7DHC->20,22(OH)2-7DHC->7-dehydropregnenolone,
      which can be further metabolized to other 5,7- steroidal dienes. These 5,7-dienal
      intermediates are converted by ultraviolet radiation B (UVB) into secosteroids
      which show pro-differentiation and anti-cancer properties. Finally, the skin is
      the site of activation of vitamin D3 through two alternative pathways. The
      classical one involves sequential hydroxylation at positions 25 and 1 to produce
      active 1,25(OH)2D3, which is further inactivated through hydroxylation at C24.
      The novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3
      which is further metabolized to biologically active but non-calcemic D3
      hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs show
      pro-differentiation, anti-proliferative and anticancer properties. In addition,
      melatonin is metabolized by local CYPs. In conclusion cutaneously expressed CYPs
      have significant effects on skin physiology and pathology trough regulation of
      its chemical milieu. 

PMID- 23869788
TI  - Intranasal infusion of nanostructured lipid carriers (NLC) containing CNS acting
      drug and estimation in brain and blood.
AB  - The present study was aimed to evaluate the nanostrucured lipid carriers (NLC)
      containing duloxetine (DLX-NLC) for intranasal infusion through the nasal cavity
      of rat. The in vivo nasal infusion studies were performed using Wistar rats and
      the amount of DLX permeated and its amount in brain and blood was estimated. The
      effects on absorption rate and type of drug delivery systems (nanocarriers and
      drug solution) for nose to brain/blood permeation were assessed. DLX was found to
      be permeated from the nasal cavity into the body of rat and the permeated amount
      was found to be more in case of DLX-NLC. Approximately 2.5-times better
      permeation was exhibited by DLX-NLC than DLX-solution. Appreciable amount of DLX
      was estimated in blood and brain and the estimated amount was higher in case of
      DLX-NLC. Thus the administration of NLC containing DLX through intranasal route
      was found to be potential method for the delivery of DLX for the treatment of
      depression.

PMID- 23869789
TI  - Pressure-sensitive mucoadhesive polymer-based dental patches to treat periodontal
      diseases: an in vitro study.
AB  - Local drug delivery for periodontal diseases is still a challenge due to very
      short residence time, involuntary swallowing and salivary wash-out. Present study
      is, therefore, an attempt to develop pressure-sensitive adhesive polymers-based
      mucoadhesive dental patches to ensure satisfactory prolonged release of drugs, to
      treat periodontal diseases locally. Polymers such as duro-tak(r) 387-2516 and
      duro-tak(r) 387, ethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol along
      with drugs amoxicillin trihydrate and diclofenac sodium were used to develop the
      experimental patches. The patches were characterized for mass variation,
      thickness, area, moisture-content and moisture-uptake, folding endurance,
      structural integrity in simulated saliva, bioadhesive strength, surface pH,
      scanning electron microscopy, cellular morphology, in vitro drug release and
      temperature-dependant stability study as per ICH guideline. Incorporation of
      release enhancers in the patches improved drug release. Drugs released in a
      sustained manner due to the formation of physical bonds between the polymers (as
      assessed by FTIR study) which might alter the length of drug diffusion pathways.
      The formulation F3 with tween 80 as release enhancer provided best drug release
      profile over the period of 8 h, thus it could be a successful attempt for the
      management of oral pathogens and dental pain.

PMID- 23869790
TI  - Energy storage studies on InVO4 as high performance anode material for Li-ion
      batteries.
AB  - InVO4 has attracted much attention as an anode material due to its high
      theoretical capacity. However, the effect of preparation methods and conditions
      on morphology and energy storage characteristic has not been extensively
      investigated and will be explored in this project. InVO4 anode material was
      prepared using five different preparation methods: solid state, urea combustion,
      precipitation, ball-milling, and polymer precursor methods. Morphology and
      physical properties of InVO4 were then analyzed using X-ray diffraction (XRD),
      scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET) surface area
      method. XRD patterns showed that orthorhombic phased InVO4 was synthesized. Small
      amounts of impurities were observed in methods II, III, and V using XRD patterns.
      BET surface area ranged from 0.49 to 9.28 m(2) g(-1). SEM images showed slight
      differences in the InVO4 nanosized crystalline structures with respect to
      preparation methods and conditions. Energy storage studies showed that, among all
      the preparation methods, the urea combustion method produced the best
      electrochemical results, with negligible capacity fading between the 2nd and 50th
      cycles and high capacity of 1241 mA h g(-1) at the end of the 20th cycle, close
      to the theoretical capacity value. Precipitation method also showed good
      performance, with capacity fading (14%) and capacity of 1002 mA h g(-1) at the
      20th cycle. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy
      (EIS) was then used to determine the reaction mechanisms of InVO4. 

PMID- 23869791
TI  - Experimental and theoretical investigation of triple fragmentation in the
      photodissociation dynamics of H2CO.
AB  - The photodissociation dynamics of H2CO molecules at energies bracketing the
      triple fragmentation threshold were investigated using velocity map ion imaging
      of the H-atom fragments. An algorithm was developed to model the experimental
      results as a two-step process: initially barrierless C-H bond fission on the S0
      potential energy surface to form H + HCO, followed by secondary fragmentation of
      those HCO radicals with sufficient internal energy to overcome the small exit
      channel barrier on the HCO surface to form H + CO. Our model treats the first
      step using phase space theory (PST) and the second using a combined PST-impulsive
      model, with a tunneling correction. Experimentally, triple fragmentation reaches
      25% of the radical (H + HCO) channel photochemical yield at energies about 1500
      cm(-1) above the barrier for breaking the second bond. In addition, the triplet
      (T1) channel appears to reduce in importance after the barrier on the T1 surface
      is exceeded, slowly decreasing to <10% of the total radical yield at higher
      energy. The double PST-impulsive model provides a good fit to the experimental H
      atom speed and energy distributions for H2CO dissociation on S0 spanning >7000
      cm(-1) of available energy. 

PMID- 23869792
TI  - Environmental reverberation affects processing of sound intensity in right
      temporal cortex.
AB  - Although sound reverberation is considered a nuisance variable in most studies
      investigating auditory processing, it can serve as a cue for loudness constancy,
      a phenomenon describing constant loudness perception in spite of changing sound
      source distance. In this study, we manipulated room reverberation characteristics
      to test their effect on psychophysical loudness constancy and we tested with
      magnetoencephalography on human subjects for neural responses reflecting loudness
      constancy. Psychophysically, we found that loudness constancy was present in
      strong, but not weak, reverberation conditions. In contrast, the dependence of
      sound distance judgment on actual distance was similar across conditions. We
      observed brain activity reflecting behavioral loudness constancy, i.e. inverse
      scaling of the evoked magnetic fields with distance for weak reverberation but
      constant responses across distance for strong reverberation from ~210 to 270 ms
      after stimulus onset. Distributed magnetoencephalography source reconstruction
      revealed underlying neural generators within the right middle temporal and right
      inferior anterior temporal lobe. Our data suggest a dissociation of loudness
      constancy and distance perception, implying a direct usage of reverberation cues
      for constructing constant loudness across distance. Furthermore, our
      magnetoencephalography data suggest involvement of auditory association areas in
      the right middle and right inferior anterior temporal cortex in this process. 

PMID- 23869793
TI  - Reversible generation of a carbon-centered radical from alkyl iodide using
      organic salts and their application as organic catalysts in living radical
      polymerization.
AB  - A new method of producing carbon-centered radicals was discovered through the
      reaction of an alkyl iodide (R-I) with organic salts to reversibly generate the
      corresponding alkyl radical (R(*)). Via this new reaction, the organic salts were
      used as new and highly efficient organic catalysts in living radical
      polymerization. The catalysts included common and inexpensive compounds such as
      tetrabutylammonium iodide and methyltributylphosphonium iodide. Notably, the
      catalysts were highly reactive. They enabled the synthesis of high-molecular
      weight polymers (up to Mn = 140,000) and the control of acrylate polymerization,
      which had been difficult with other organic catalysts. The organic salt catalysts
      were highly versatile, reacting with methacrylate, acrylate, styrene,
      acrylonitrile, and functional methacrylate monomers. Well-defined block
      copolymers were also prepared by using this method. A kinetic study
      quantitatively confirmed the high reactivity of these catalysts. Attractive
      features of this system include its low cost, its ease of operation, and its
      ability to access a wide range of polymer designs.

PMID- 23869794
TI  - Chronic atrial fibrillation alters the functional properties of If in the human
      atrium.
AB  - INTRODUCTION: Despite the evidence that the hyperpolarization-activated current
      (If) is highly modulated in human cardiomyopathies, no definite data exist in
      chronic atrial fibrillation (cAF). We investigated the expression, function, and
      modulation of If in human cAF. METHODS AND RESULTS: Right atrial samples were
      obtained from sinus rhythm (SR, n = 49) or cAF (duration >1 year, n = 31)
      patients undergoing corrective cardiac surgery. Among f-channel isoforms
      expressed in the human atrium (HCN1, 2 and 4), HCN4 mRNA levels measured by RT
      PCR were significantly reduced. However, protein expression was preserved in cAF
      compared to SR (+85% for HCN4); concurrently, miR-1 expression was significantly
      reduced. In patch-clamped atrial myocytes, current-specific conductance (gf) was
      significantly increased in cAF at voltages around the threshold for If activation
      (-60 to -80 mV); accordingly, a 10-mV rightward shift of the activation curve
      occurred (P < 0.01). beta-Adrenergic and 5-HT4 receptor stimulation exerted
      similar effects on If in cAF and SR cells, while the ANP-mediated effect was
      significantly reduced (P < 0.02), suggesting downregulation of natriuretic
      peptide signaling. CONCLUSIONS: In human cAF modifications in transcriptional and
      posttranscriptional mechanisms of HCN channels occur, associated with a slight
      yet significant gain-of-function of If , which may contribute to enhanced atrial
      ectopy.

PMID- 23869795
TI  - Considering the balance: development of a scale to assess patient views on trade
      offs in competing health outcomes.
AB  - OBJECTIVES: To describe the development of a scale assessing participant
      attitudes regarding two commonly encountered trade-offs: quality versus quantity
      of life and present versus future health. DESIGN: Observational cohort study.
      SETTING: Community. PARTICIPANTS: Three hundred and fifty-seven community
      dwelling adults aged 65 and older. MEASUREMENTS: An initial set of 20 items rated
      on a 5-point Likert scale of agreement was reduced using principal components
      analysis. Construct validity was evaluated through comparison of the scale with
      other tools addressing the same trade-offs and analysis of participant
      characteristics associated with attitudes favoring quality over quantity of life
      and present over future health. Internal consistency was assessed using Cronbach
      alpha. Test-retest reliability was assessed using intraclass correlation
      coefficients (ICCs). RESULTS: The scale consists of two subscales, each
      addressing one trade-off, with a total of 10 items. All factor loadings were 0.5
      and greater, and subscale scores were significantly different (P <= .05) in the
      expected directions when comparing with other tools and with participant race,
      education, and religious identity. Internal consistency was good (Cronbach alpha
      0.85 and 0.84), and test-retest reliability was fair (ICCs 0.63 and 0.47).
      Subscale score medians fell near the middle of each scale, with narrow
      interquartile ranges, but more than 15% of the sample scored at an extreme of
      each subscale. CONCLUSION: This new scale captures views on two common trade-offs
      in health care. Although test-retest reliability was modest, its high validity
      suggests that this tool can be used to familiarize people with common trade-offs
      and further explore influences on attitudes.

PMID- 23869796
TI  - Benefit finding and resilience in child caregivers.
AB  - OBJECTIVES: A substantial number of children are involved in informal caregiving
      and make a significant contribution to health care delivery. While this places
      high levels of demand on their coping resources, there is some evidence that
      these children find benefit in their caring role. DESIGN: A survey design using
      questionnaire data collection was used with a sample of 442 children (174 boys
      and 268 girls) between the ages of 12 and 16. METHODS: The role of benefit
      finding and resilience was explored within a stress and coping model of the
      impact of caregiving. RESULTS: Hierarchical multiple regression analysis (HMRA)
      identified resilience and benefit finding as accounting for significant amounts
      of variance in positive health and mediating the impact of caregiving. In regard
      to negative health, only benefit finding played a significant role. CONCLUSIONS:
      Young caregivers do experience benefit finding and exhibit resilience although
      the relationship with caregiving burden was inverse. Benefit finding seems to be
      related to social recognition of the caregiving role and to family support.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? There is some
      emerging evidence that child caregivers experience some positive effects or
      benefits from their caring in spite of the demands of the role. However, the main
      focus has been on reducing negative outcomes rather than on building resilience.
      What this study adds? This study provides evidence that young caregivers do
      experience benefit finding in situations where the role demand is not overly
      excessive and where the role is socially recognized.

PMID- 23869797
TI  - Practices in diagnosis, disclosure and pharmacotherapeutic management of dementia
      by general practitioners--a national survey.
AB  - OBJECTIVES: To explore the practice patterns of general practitioners (GPs) for
      the diagnosis, disclosure and pharmacological management of individuals with
      dementia. We also investigated whether the number of years working in general
      practice is a determinant factor associated with the responses obtained. METHOD:
      A national survey was sent to all registered GPs in the Maltese islands. The
      return rate was 54.2% with the majority of respondents having 15 years or more
      working experience in general practice. Chi-square analysis of variance was used
      to determine any relationship effects. RESULTS: Although the majority of GPs
      indicated lack of competence in diagnosing dementia, only a small percentage
      showed a preference towards specialist referral. Lack of training was mostly
      envisaged by physicians with the least number of years in general practice.
      Significant differences in pharmacotherapeutic prescribing were noted depending
      on the stage of disease progression and the number of years working as a GP.
      Disease disclosure was not routinely carried out even though GPs were aware of
      the fact that disclosure may help individuals with dementia and their caregivers
      or relatives with future planning. CONCLUSION: The findings show notable
      shortcomings in various aspects of dementia management by GPs. This highlights
      the need of providing continued educational support and training opportunities to
      enhance not only GPs' clinical competence, but also their role as key players in
      providing quality support to individuals with dementia in the primary care
      setting.

PMID- 23869798
TI  - Transforming growth factor (TGF)-beta signalling is increased in rheumatoid
      synovium but TGF-beta blockade does not modify experimental arthritis.
AB  - The aim of this study was to analyse the distribution of regulatory and
      inhibitory mothers against decapentaplegic homologue (Smad) proteins as markers
      of active transforming growth factor (TGF)-beta signalling in rheumatoid
      arthritis (RA) synovial tissue and to investigate the effect of TGF-beta blockade
      in the development and progression of collagen-induced arthritis. The expression
      of Smad proteins in synovial tissues from RA, osteoarthritic and healthy controls
      was analysed by immunohistochemistry. Arthritis was induced in DBA/1 mice by
      immunization with chicken type-II collagen (CII). TGF-beta was blocked in vivo
      with the specific peptide p17 starting at the time of immunization or on the day
      of arthritis onset. T cell population frequencies and specific responses to CII
      were analysed. The expression of cytokines and transcription factors was
      quantified in spleen and joint samples. Statistical differences between groups
      were compared using the Mann-Whitney U-test or one-way analysis of variance
      (anova) using the Kruskal-Wallis test. p-Smad-2/3 and inhibitory Smad-7
      expression were detected in RA and control tissues. In RA, most lymphoid
      infiltrating cells showed nuclear p-Smad-2/3 without Smad-7 expression. Treatment
      with TGF-beta antagonist did not affect clinical severity, joint inflammation and
      cartilage damage in collagen-induced arthritis. Frequency of T cell subsets, mRNA
      levels of cytokines and transcription factors, specific proliferation to CII,
      serum interleukin (IL)-6 and anti-CII antibodies were comparable in p17 and
      phosphate-buffered saline (PBS)-treated groups. The pattern of Smad proteins
      expression demonstrates active TGF-beta signalling in RA synovium. However,
      specific TGF-beta blockade does not have a significant effect in the mice model
      of collagen-induced arthritis. 

PMID- 23869799
TI  - Fire, hurricane and carbon dioxide: effects on net primary production of a
      subtropical woodland.
AB  - Disturbance affects most terrestrial ecosystems and has the potential to shape
      their responses to chronic environmental change. Scrub-oak vegetation
      regenerating from fire disturbance in subtropical Florida was exposed to
      experimentally elevated carbon dioxide (CO2) concentration (+350 MUl l(-1)) using
      open-top chambers for 11 yr, punctuated by hurricane disturbance in year 8. Here,
      we report the effects of elevated CO2 on aboveground and belowground net primary
      productivity (NPP) and nitrogen (N) cycling during this experiment. The
      stimulation of NPP and N uptake by elevated CO2 peaked within 2 yr after
      disturbance by fire and hurricane, when soil nutrient availability was high. The
      stimulation subsequently declined and disappeared, coincident with low soil
      nutrient availability and with a CO2 -induced reduction in the N concentration of
      oak stems. These findings show that strong growth responses to elevated CO2 can
      be transient, are consistent with a progressively limited response to elevated
      CO2 interrupted by disturbance, and illustrate the importance of biogeochemical
      responses to extreme events in modulating ecosystem responses to global
      environmental change.

PMID- 23869800
TI  - Prevalence of carcinoma in situ in testicular biopsies of infertile Iranian men.
AB  - Almost all testicular germ cell tumours are proved to originate from carcinoma in
      situ cells. Infertility is one of the factors that increase the risk of carcinoma
      in situ. The reported prevalence for carcinoma in situ from different parts of
      the world is 0-3.7% in infertile men. This retrospective study was performed to
      determine the prevalence of carcinoma in situ in Iranian infertile men. We
      reviewed the testicular biopsies of 1153 infertile men at the pathology
      department of Avicenna Infertility Center. One hundred and fifty-one cases were
      suspicious of having carcinoma in situ. Immunohistochemical marker for placental
      alkaline phosphatase was employed to confirm the diagnosis of carcinoma in situ.
      Positive results were detected in 7 (0.6%) of 1153 cases (95% CI 0.24%-1.24%), 6
      (0.94%) of which (95% CI 0.34%-2.04%) were under the age of 35 years (636
      patients were in this age group). This study is the first study in Iran
      determining the prevalence of carcinoma in situ among the infertile Iranian men;
      the result is in the range of reports from other countries. 

PMID- 23869801
TI  - Peri-anaesthetic mortality in horses - the need for CEPEF-4.

PMID- 23869802
TI  - Intramolecular displacement of phenylselenone by a hydroxy group: stereoselective
      synthesis of 2-substituted tetrahydrofurans.
AB  - An efficient and stereocontrolled synthesis of 2-substituted tetrahydrofurans has
      been achieved. The approach employs the asymmetric reduction of gamma
      phenylseleno ketones obtained by three different procedures that are peculiarly
      applied to the synthesis of such compounds. Finally, the intramolecular
      substitution of the phenylselenone residue by the oxygen atom of a hydroxy group
      gives the tetrahydrofuran ring. 

PMID- 23869803
TI  - Biased attentional engagement with, and disengagement from, negative information:
      independent cognitive pathways to anxiety vulnerability?
AB  - Cognitive models of anxiety propose that selective attention to negative
      information plays a causal role in heightened anxiety vulnerability and
      dysfunction. However, there has been theoretical disagreement concerning whether
      anxiety-linked attentional biases reflect enhanced attentional engagement with,
      or impaired attentional disengagement from, negative information. We contend that
      previous methodologies have not been optimal in terms of their capacity to
      differentiate both types of bias. The present study introduces a refined
      methodology, in which the conventional dot-probe task is modified in a novel
      manner to enable the independent assessment of these components of attention. The
      findings demonstrate that facilitated attentional engagement and impaired
      attentional disengagement are both characteristic of elevated levels of anxiety
      vulnerability. Moreover, these prove to be unrelated facets of attentional
      selectivity that independently contribute to variation in anxiety vulnerability.
      We discuss the possibility that these two types of attentional bias may represent
      independent pathways to anxiety vulnerability. 

PMID- 23869805
TI  - Additional information on the role of histopathology in diagnosing diabetic foot
      osteomyelitis.

PMID- 23869806
TI  - Impact of warming on phyto-bacterioplankton coupling and bacterial community
      composition in experimental mesocosms.
AB  - Global warming is assumed to alter the trophic interactions and carbon flow
      patterns of aquatic food webs. The impact of temperature on phyto
      bacterioplankton coupling and bacterial community composition (BCC) was the focus
      of the present study, in which an indoor mesocosm experiment with natural
      plankton communities from the western Baltic Sea was conducted. A 6  degrees C
      increase in water temperature resulted, as predicted, in tighter coupling between
      the diatom-dominated phytoplankton and heterotrophic bacteria, accompanied by a
      strong increase in carbon flow into bacterioplankton during the phytoplankton
      bloom phase. Suppressed bacterial development at cold in situ temperatures
      probably reflected lowered bacterial production and grazing by protists, as the
      latter were less affected by low temperatures. BCC was strongly influenced by the
      phytoplankton bloom stage and to a lesser extent by temperature. Under both
      temperature regimes, Gammaproteobacteria clearly dominated during the
      phytoplankton peak, with Glaciecola sp. as the single most abundant taxon.
      However, warming induced the appearance of additional bacterial taxa belonging to
      Betaproteobacteria and Bacteroidetes. Our results show that warming during an
      early phytoplankton bloom causes a shift towards a more heterotrophic system,
      with the appearance of new bacterial taxa suggesting a potential for utilization
      of a broader substrate spectrum.

PMID- 23869807
TI  - The gene expression analysis of paracrine/autocrine factors in patients with
      spermatogenetic failure compared with normal spermatogenesis.
AB  - PROBLEM: The aim of this study was to examine the expression levels of IL-1
      family members, IL-6, IL-10, TNF family, SCF, and c-kit in infertile patients
      with idiopathic non-obstructive azoospermia (NOA) compared with men with normal
      spermatogenesis. METHOD OF STUDY: We analyzed 20 testicular biopsy samples with
      Affymetrix Human Gene 1.0 ST microarrays (Affymetrix, Santa Clara, CA, USA).
      Sixteen of them were obtained from patients with various types of NOA and four
      with normal spermatogenesis. RESULTS: The comparative analysis of normal and
      pathological group demonstrated a different expression level of IL1-RA gene. It
      was also observed that the gene expression levels for IL1-R1, CASP1, and stem
      cell factor (SCF) were upregulated in the Sertoli-cell-only syndrome group in
      comparison with the control one (P < 0.05). CONCLUSION: The microarray analysis
      showed the expression level of all investigated paracrine/autocrine factors at
      one go, and therefore, the possible interaction between these genes could be
      examined.

PMID- 23869808
TI  - Nanoparticle- and liposome-carried drugs: new strategies for active targeting and
      drug delivery across blood-brain barrier.
AB  - The blood-brain barrier (BBB), the unusual microvascular endothelial interface
      between the central nervous system (CNS) and the circulatory system, is a major
      hindrance to drug delivery in the brain parenchyma. Besides the absence of
      fenestrations and the abundance of tight junctions, ATP-binding cassette (ABC)
      transporters critically reduce drug entry within the CNS, as they carry many
      drugs back into the bloodstream. Nanoparticle- and liposome-carried drugs,
      because of their increased cellular uptake and reduced efflux through ABC
      transporters, have been developed in recent times to circumvent the low drug
      permeability of the BBB. This review discusses the role of ABC transporters in
      controlling drug penetration into the brain parenchyma, the rationale for using
      nanoparticle- and liposome-based strategies to increase drug delivery across the
      BBB and new therapeutic strategies for using nanoparticle- and liposome-carried
      drugs in different conditions, ranging from CNS tumors and neurodegenerative
      diseases to viral infections and epilepsy. 

PMID- 23869809
TI  - Trichothecenes: structure-toxic activity relationships.
AB  - Trichothecenes comprise a large family of structurally related toxins mainly
      produced by fungi belonging to the genus Fusarium. Among trichothecenes, type A
      and type B are of the most concern due to their broad and highly toxic nature. In
      order to address structure-activity relationships (SAR) of trichothecenes,
      relationships between structural features and biological effects of trichothecene
      mycotoxins in mammalian systems are summarized in this paper. The double bond
      between C-9-C-10 and the 12,13-epoxide ring are essential structural features for
      trichothecene toxicity. Removal of these groups results in a complete loss of
      toxicity. A hydroxyl group at C-3 enhances trichothecene toxicity, while this
      activity decreases gradually when C-3 is substituted with either hydrogen or an
      acetoxy group. The presence of a hydroxyl group at C-4 promotes slightly lower
      toxicity than an acetoxy group at the same position. The toxicity for type B
      trichothecenes decreases if the substituent at C-4 is changed from acetoxy to
      hydroxyl or hydrogen at C-4 position. The presence of hydroxyl and hydrogen
      groups on C-15 decreases the trichothecene toxicity in comparison with an acetoxy
      group attached to this carbon. Trichothecenes toxicity increases when a
      macrocyclic ring exists between the C-4 and C-15. At C-8 position, an oxygenated
      substitution at C-8 is essential for trichothecene toxicity, indicating a
      decrease in the toxicity if substituent change from isovaleryloxy through
      hydrogen to the hydroxyl group. The presence of a second epoxy ring at C-7-C-8
      reduces the toxicity, whereas epoxidation at C-9-C-10 of some macrocyclic
      trichothecenes increases the activity. Conjugated trichothecenes could release
      their toxic precursors after hydrolysis in animals, and present an additional
      potential risk. The SAR study of trichothecenes should provide some crucial
      information for a better understanding of trichothecene chemical and biological
      properties in food contamination. 

PMID- 23869810
TI  - Polymer-based cancer nanotheranostics: retrospectives of multi-functionalities
      and pharmacokinetics.
AB  - The pressing need for targeting, detecting, monitoring, and treating diseased
      cells concomitantly gives rise to multi-functional nanomedicines, especially
      those that can combine diagnostic and therapeutic abilities, which are referred
      to as nanotheranostics. Recently, nanotheranostics are of significant clinical
      interest as these nanomedicines offer new opportunities to directly visualize
      drug blood circulation and biodistribution, thus facilitating the development of
      more personalized treatment regimens. To date, much research has shown the
      exciting potential of nanotheranostics in cancer therapy and imaging. In
      particular, the advancements of polymeric nanomaterials in the past decades have
      paved the way for the development of cancer nanotheranostics that are primarily
      comprised of polymers or conjugates of polymer and other types of nanomaterials
      such as gold nanoparticles, quantum dots, carbon nanotubes, and magnetic iron
      oxide nanoparticles. Additionally, to improve the therapeutic and diagnostic
      efficiency of cancer nanotheranostics, various strategies have been utilized to
      provide targeted-delivery across biological barriers and environmental-responsive
      delivery, leading to the alteration of pharmacokinetics such as drug
      distribution, cellular partition, and elimination routes. In this review, we will
      summarize recent development of polymer-based cancer nanotheranostics and some
      novel strategies to improve their pharmacokinetics, especially biodistribution,
      followed by a brief discussion of their applications in cancer therapies as well
      as their toxicity and safety. 

PMID- 23869811
TI  - Prodrug design targeting intestinal PepT1 for improved oral absorption: design
      and performance.
AB  - Oligopeptide transporter 1 (PepT1) plays an essential role in the oral absorption
      of di-and tripeptides from the digestion of ingested protein. PepT1 has become a
      striking prodrug-designing target recently, since some poorly absorbed drugs can
      be modified as peptidomimetic prodrugs targeting intestinal PepT1 to improve
      membrane permeability, and eventually oral absorption of the parent drug.
      However, little and no comprehensive attempts have been made to especially focus
      on the recent developments of prodrugs targeting intestinal PepT1. This article
      summarized biology, transport mechanism, structure-transport requirements for
      PepT1 and significant advances on the PepT1-targeted prodrugs within the two
      decades. The article also aimed to highlight some inspirations and knowledge on
      the multifunctional PepT1-targeted design, which are necessary for obtaining
      optimal prodrug candidates. That is the requirements of multifunctional rational
      PepT1 prodrugs include enough binding affinity for PepT1, controlled or targeted
      release of parent drug, escapement from P-gp mediated efflux and enhanced
      chemical/metabolic stability. Several types of peptidomimetic prodrugs reported
      recently were discussed in detail in this review. 

PMID- 23869812
TI  - Pharmacogenetics, pharmacogenomics and epigenetics of Nrf2-regulated xenobiotic
      metabolizing enzymes and transporters by dietary phytochemical and cancer
      chemoprevention.
AB  - Cancer chemopreventive activities of various phytochemicals have been attributed
      to the modulation of xenobiotic disposition, which includes absorption,
      distribution, metabolism, and excretion. The interaction between xenobiotics and
      xenobiotic-metabolizing enzymes (XMEs) is bidirectional. XMEs are responsible for
      the biotransformation of xenobiotics such as bioactivation and detoxification.
      Conversely, xenobiotics affect XMEs through transcriptional regulation (induction
      or suppression) and post-translational interactions (inhibition or activation).
      Similar relationships also exist between xenobiotics and their transporters.
      Studies conducted over the past decade have demonstrated that the transcription
      factor, nuclear factor erythroid 2-related factor 2 (Nrf2), plays a critical role
      in the regulation of detoxifying enzymes and transporters through a signaling
      system that senses and responds to redox imbalance. The role of Nrf2 in the
      interaction between chemopreventive phytochemicals and detoxifying
      enzymes/transporters has become an important topic in cancer chemoprevention. In
      this review, the genetic and epigenetic factors that contribute to Nrf2-mediated
      regulation of detoxifying XMEs and transporters are discussed in the context of
      cancer chemoprevention. Phytochemicals may modulate the genome as well as
      epigenome, altering the regulation of XMEs and transporters, which may be
      critical for both cancer chemoprevention and the prevention of other oxidative
      stress- and inflammatory-related diseases, including cardiovascular, metabolic
      and neurological pathologies. The pharmacogenomic expression of XMEs and
      transporters, with an emphasis on both genomics and epigenetics, will also be
      discussed. 

PMID- 23869813
TI  - Demographic evidence of illegal harvesting of an endangered asian turtle.
AB  - Harvesting pressure on Asian freshwater turtles is severe, and dramatic
      population declines of these turtles are being driven by unsustainable collection
      for food markets, pet trade, and traditional Chinese medicine. Populations of big
      headed turtle (Platysternon megacephalum) have declined substantially across its
      distribution, particularly in China, because of overcollection. To understand the
      effects of chronic harvesting pressure on big-headed turtle populations, we
      examined the effects of illegal harvesting on the demography of populations in
      Hong Kong, where some populations still exist. We used mark-recapture methods to
      compare demographic characteristics between sites with harvesting histories and
      one site in a fully protected area. Sites with a history of illegal turtle
      harvesting were characterized by the absence of large adults and skewed ratios of
      juveniles to adults, which may have negative implications for the long-term
      viability of populations. These sites also had lower densities of adults and
      smaller adult body sizes than the protected site. Given that populations
      throughout most of the species' range are heavily harvested and individuals are
      increasingly difficult to find in mainland China, the illegal collection of
      turtles from populations in Hong Kong may increase over time. Long-term
      monitoring of populations is essential to track effects of illegal collection,
      and increased patrolling is needed to help control illegal harvesting of
      populations, particularly in national parks. Because few, if any, other
      completely protected populations remain in the region, our data on an unharvested
      population of big-headed turtles serve as an important reference for assessing
      the negative consequences of harvesting on populations of stream turtles.
      Evidencia Demografica de la Captura Ilegal de una Tortuga Asiatica en Peligro. 

PMID- 23869814
TI  - Effect of linear nonionic polymer additives on the kinetic stability of
      dispersions of poly(diallyldimethylammonium chloride)/sodium dodecylsulfate
      nanoparticles.
AB  - In this article, the impact of different neutral polymers on the kinetic
      stability of charge-stabilized poly(diallyldimethylammonium chloride)
      (PDADMAC)/sodium dodecylsulfate (SDS) colloidal dispersions is analyzed using
      dynamic light scattering, electrophoretic mobility, turbidity, and coagulation
      kinetics measurements. Poly(ethyleneoxide) (PEO), poly(vinylpyrrolidone) (PVP),
      and dextran of comparable molecular masses as well as a higher-molecular-weight
      dextran sample were tested as nonionic additives. The light scattering and
      mobility data indicate that the PEO and PVP molecules may adsorb on the surface
      of the PDADMAC/SDS nanoparticles formed in the presence of excess surfactant. The
      primary effect of these additives is manifested in enhanced coagulation of the
      PDADMAC/SDS nanoparticles due to bridging at lower polymer concentrations and
      depletion flocculation at higher polymer concentrations. These findings are in
      sharp contrast to the earlier published effect of the same nonionic polymers on
      the poly(ethyleneimine) (PEI)/SDS colloidal dispersions, which can be sterically
      stabilized at appropriate PEO or PVP concentrations. However, the adsorption of
      the investigated dextran samples is negligible on the PDADMAC/SDS nanoparticles.
      Therefore, dextran molecules may cause only depletion flocculation in the
      PDADMAC/SDS system in the vicinity of the critical overlap concentration. 

PMID- 23869815
TI  - Geographic disparities in access to cancer care: do patients in outlying areas
      talk about their access problems to their general practitioners and medical
      oncologists and how does that impact on the choice of chemotherapy?
AB  - Geographic disparities in access to cancer care have been reported for several
      countries. The distance between the place of residence and the cancer care centre
      can be one cause of these disparities. Solutions to surmount the barriers can be
      found if patients talk about this to their care professionals. We investigated
      whether patients in Valais talk with their physicians about difficulties to
      access cancer care. We interviewed five general practitioners and five medical
      oncologists in Valais with semi-structured interviews to identify difficulties
      patients are talking about. Medical oncologists were also interviewed on their
      habits to adapt chemotherapy to access problems of their patients. Cancer
      patients in Valais do talk about their access problems. Medical oncologists in
      Valais do take access problems into account when discussing therapeutic options
      with the patients and use the scope they have within their therapeutic options.
      In Valais the family of cancer patients play an important role in access to
      cancer care. Special offers are in place when social support is insufficient.
      Whether some socio-economic minorities do not use the solutions in place cannot
      be answered and should be investigated in further studies. 

PMID- 23869816
TI  - The existential life situations of spouses of persons with dementia before and
      after relocating to a nursing home.
AB  - OBJECTIVES: The aim was to describe the existential life situations of spouses
      who care for persons with dementia, before and after relocation to nursing homes.
      METHOD: This was a qualitative study among 11 spouses of persons with dementia,
      recruited via purposeful sampling. Data were collected through interviews and
      analysed with interpretive content analysis. RESULTS: Before the relocation to
      nursing homes, the spouses' existential life situations were characterized by
      feelings of shame and guilt, being isolated in the home. Spouses were also
      exposed to psychological threats, physical violence, and had feelings of placing
      one's own needs last. After the relocation, spouses described feelings of guilt
      and freedom, living with grief and thoughts of death, feelings of loneliness in
      the spousal relationship, and striving for acceptance despite a lack of
      completion. CONCLUSION: The existential life situation of spouses of persons with
      dementia is about being in limit situations which changes when the ill person
      relocates to a nursing home. This is important knowledge for health care staff to
      bear in mind at nursing homes when encountering spouses.

PMID- 23869817
TI  - Ratiometric nanothermometer based on an emissive Ln3+-organic framework.
AB  - Luminescent thermometers working at the nanoscale with high spatial resolution,
      where the conventional methods are ineffective, have emerged over the last couple
      of years as a very active field of research. Lanthanide-based materials are among
      the most versatile thermal probes used in luminescent nanothermometers. Here,
      nanorods of metal organic framework Tb0.99Eu0.01(BDC)1.5(H2O)2 (BDC = 1-4
      benzendicarboxylate) have been prepared by the reverse microemulsion technique
      and characterized and their photoluminescence properties studied from room
      temperature to 318 K. Aqueous suspensions of these nanoparticles display an
      excellent performance as ratiometric luminescent nanothermometers in the
      physiological temperature (300-320 K) range. 

PMID- 23869818
TI  - Facile green in situ synthesis of Mg/CuO core/shell nanoenergetic arrays with a
      superior heat-release property and long-term storage stability.
AB  - We report a facile green method for the in situ synthesis of Mg/CuO core/shell
      nanoenergetic arrays on silicon, with Mg nanorods as the core and CuO as the
      shell. Mg nanorods are first prepared by glancing angle deposition. CuO is then
      deposited around the Mg nanorods by reactive magnetron sputtering to realize the
      core/shell structure. Various characterization techniques are used to investigate
      the prepared Mg/CuO core/shell nanoenergetic arrays, including scanning electron
      microscopy, transmission electron microscopy, X-ray energy dispersive
      spectroscopy, X-ray diffraction, and thermal analysis. Uniform mixing and
      intimate contact between the Mg nanorods and CuO are confirmed from both visual
      inspection of the morphological images and analyses of the heat-release curves.
      The nanoenergetic arrays exhibit a low-onset reaction temperature (~300  degrees
      C) and high heat of reaction (~3400 J/g). Most importantly, the nanoenergetic
      arrays possess long-term storage stability resulting from the stable CuO shell.
      This study provides a potential general strategy for the synthesis of various Mg
      nanorod-based stable nanoenergetic arrays. 

PMID- 23869819
TI  - Can the unauthorised use of ceftiofur be detected in poultry?
AB  - Ceftiofur is a third-generation cephalosporin antibiotic used to treat cattle and
      swine for bacterial infection of the respiratory tract. It is not authorised for
      use in poultry within the European Union. Due to the complexity of the chemistry
      and metabolism of ceftiofur, maximum residue limits (MRLs) are based on
      desfuroylceftiofur (DFC) equivalents after chemical conversion of all compounds
      that have an intact beta-lactam ring. In practice the DFC is usually stabilised
      as the acetamide (desfuroylceftiofur acetamide - DFCA) for analysis. Because of
      recent evidence of off-label use in the European Union, a policy need emerged to
      develop a cost-effective method for the detection of ceftiofur residues in
      poultry tissues. One-day-old chicks were each dosed subcutaneously with ceftiofur
      and samples taken from day 1 to day 44 post-dosing. Residues of ceftiofur parent
      compound were detected in whole chicks, wing feathers and faeces. On the basis of
      this finding it was decided to evaluate ceftiofur parent, as the marker, instead
      of proceeding with the time-consuming conversion to DFCA. Expected metabolites,
      DFC and desfuroylceftiofur cysteine disulfide (DCCD), were not detected in whole
      chicks, muscle or liver, but DFC was found in wing feathers. These results
      indicate that determination of ceftiofur parent compound in either whole chicks
      or possibly wing feathers and faeces may allow the detection of the misuse of
      ceftiofur. 

PMID- 23869820
TI  - Temperature response of in vivo Rubisco kinetics and mesophyll conductance in
      Arabidopsis thaliana: comparisons to Nicotiana tabacum.
AB  - Biochemical models are used to predict and understand the response of
      photosynthesis to rising temperatures and CO2 partial pressures. These models
      require the temperature dependency of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco) kinetics and mesophyll conductance to CO2 (g(m)).
      However, it is not known how the temperature response of Rubisco kinetics differs
      between species, and comprehensive in vivo Rubisco kinetics that include gm have
      only been determined in the warm-adapted Nicotiana tabacum. Here, we measured the
      temperature response of Rubisco kinetics and gm in N. tabacum and the cold
      adapted Arabidopsis thaliana using gas exchange and (13)CO2 isotopic
      discrimination on plants with genetically reduced levels of Rubisco. While the
      individual Rubisco kinetic parameters in N. tabacum and A. thaliana were similar
      across temperatures, they collectively resulted in significantly different
      modelled rates of photosynthesis. Additionally, gm increased with temperature in
      N. tabacum but not in A. thaliana. These findings highlight the importance of
      considering species-dependent differences in Rubisco kinetics and gm when
      modelling the temperature response of photosynthesis.

PMID- 23869821
TI  - History of antibiotics: from fluoroquinolones to daptomycin (Part 2).
AB  - In the Modern Era, physicians attested to the reciprocal influence among a
      technologically advanced society, rapid scientific progresses in medicine, and
      the need for new antimicrobials. The results of these changes were not only seen
      in the prolongation of life expectancy but also by the emergence of new
      pathogens. We first observed the advent of Gram-negative bacteria as a major
      source of nosocomial infections. The treatment of these microorganisms was
      complicated by the appearance and spread of drug resistance. We first focused on
      the development of two major classes of antimicrobials still currently used for
      the treatment of Gram-negative bacteria, such as fluoroquinolones and
      carbapenemes. Subsequently, we directed our attention to the growth of the
      incidence of infections due to Methicillin-Resistant Staphylococcus aureus
      (MRSA). Although the first MRSA was already isolated in 1961, the treatment of
      this new pathogen has been based on the efficacy of vancomycin for more than four
      decades. Only in the last 15 yr, we assisted in the development of new
      antimicrobial agents such as linezolid and daptomycin.

PMID- 23869822
TI  - Suture-free and mesh reinforced small intestinal anstomoses: a feasibility study
      in rabbits.
AB  - INTRODUCTION: Anastomotic leakage still remains a major complication in general
      surgery. Beside general risk factors, the ideal method of anastomotic technique
      has not been found until now. The aim of the present study was to analyze wound
      healing in suture-free small intestine anastomoses using fibrin glue with and
      without mesh-reinforcement. METHODS: Laparotomy and four different types of small
      bowel anastomoses were performed in 32 chinchilla rabbits. Standard hand-sewn
      anastomoses (CG), suture-free glued anastomoses (FG) with and without mesh
      reinforcement using two different types of meshes [Vicryl-mesh (VM) and Surgisis
      (SM)]. Animals were sacrificed after 5 and 21 days. Bursting pressure, collagen
      type I/III ratio, and matrix-metalloproteinase 2, 9, and 13 were analyzed.
      RESULTS: None of the animals died due to an anastomotic leakage. All animals in
      the long term group with Surgisis mesh died due to a mechanical bowel obstruction
      based on a distinctive stenosis of the anastomosis. The bursting pressures did
      significantly differed in animals with fibrin glue alone compared to animals with
      Vicryl-mesh reinforcement (p < 0.05). Histological examination revealed
      statistically significant differences (p < 0.05) in the values for MMP-2 (VM <
      SM), MMP-9 (VM < CG), and MMP-13 (CG < SM, VM < FG, and VM < SM). However,
      collagen type I/III ratios were not significantly different between groups.
      CONCLUSIONS: Our results suggest that a mesh reinforced glued anastomosis is
      technically feasible. Furthermore, mesh-reinforcement using VM increased the
      integrity and simplified the technique of suture-free anastomoses.

PMID- 23869823
TI  - Associations between selected allergens, phthalates, nicotine, polycyclic
      aromatic hydrocarbons, and bedroom ventilation and clinically confirmed asthma,
      rhinoconjunctivitis, and atopic dermatitis in preschool children.
AB  - Previous studies, often using data from questionnaires, have reported
      associations between various characteristics of indoor environments and allergic
      disease. The aim of this study has been to investigate possible associations
      between objectively assessed indoor environmental factors and clinically
      confirmed asthma, rhinoconjunctivitis, and atopic dermatitis. The study is a
      cross-sectional case-control study of 500 children aged 3-5 years from Odense,
      Denmark. The 200 cases had at least two parentally reported allergic diseases,
      while the 300 controls were randomly selected from 2835 participating families. A
      single physician conducted clinical examinations of all 500 children. Children
      from the initially random control group with clinically confirmed allergic
      disease were subsequently excluded from the control group and admitted in the
      case group, leaving 242 in the healthy control group. For most children, specific
      IgE's against various allergens were determined. In parallel, dust samples were
      collected and air change rates were measured in the children's bedrooms. The dust
      samples were analyzed for phthalate esters, polycyclic aromatic hydrocarbons
      (PAH), nicotine, and various allergens. Among children diagnosed with asthma,
      concentrations of nicotine were higher (P < 0.05) and cat allergens were lower (P
      < 0.05) compared with the healthy controls; air change rates were lower for those
      sensitized (specific IgE+) compared with those not sensitized (specific IgE-, P <
      0.05); and dust mite allergens were higher for specific IgE+ cases compared with
      healthy controls (P < 0.05). When disease status was based solely on
      questionnaire responses (as opposed to physician diagnosis), significant
      associations were found between di(2-ethylhexyl) phthalate (DEHP) and dog
      allergens in dust and current wheeze. 

PMID- 23869824
TI  - Gait characteristics of multiple sclerosis patients in the absence of clinical
      disability.
AB  - PURPOSE: Motor deficits in lower extremities and gait abnormalities are a major
      feature of the multiple sclerosis (MS) patients. Patients with minimal clinical
      disability have subtle gait changes. The aim of this study was to analyze the
      gait characteristics of MS patients in the absence of clinical disability.
      METHOD: A case-control study was carried out with 12 MS patients and 12 matched
      healthy controls. The subjects underwent a clinical neurological evaluation to
      determine their disability level (EDSS <= 1.5). Then, the subjects were referred
      for completion self-report questionnaires (gait, perceived balance confidence,
      physical activity and fatigue), gait clinical trials, and 3D kinematic analysis.
      RESULTS: MS patients showed more impairment of perceived fatigue, perceived of
      walking impact and perceived balance confidence, despite having no disability.
      Gait characteristics showed no differences when they were determined by clinical
      observation. The 3D kinematic analysis of gait showed slight but significant
      changes in ankle movement. CONCLUSION: MS patients with no clinical disability
      have discrete changes in gait that can be evidenced by perceived impact on
      walking and kinematic evaluation, mainly of ankle movement. Moreover, there is a
      decrease in perceived balance confidence and an increase in perceived fatigue,
      which are correlated despite having different origins.

PMID- 23869825
TI  - Photophysics of soret-excited tin(IV) porphyrins in solution.
AB  - The photophysics of low-chlorin tin(IV) tetraphenylporphyrin dihydroxide, a core
      building block for axially substituted supramolecular tin porphyrin constructs,
      has been studied in a variety of hydrogen-bonding, nonpolar, and aprotic polar
      solvents using steady-state, nanosecond, and femtosecond time-resolved emission,
      and femtosecond time-resolved absorption methods. In hydrogen-bonding solvents
      the metalloporphyrin exists as solvated monomers, and its Soret-excited S2 state
      in these solvents exhibits the expected linear energy gap law relationship with
      first-order population decay times in the 0.8 to 1.7 ps range. Evidence is
      presented that this metalloporphyrin aggregates in other solvents at the
      concentrations typically used for these ultrafast measurements and yields species
      averaged time-resolved data. Cw laser excitation in the Q-band under deaerated
      conditions produces weak S2-S0 fluorescence (photon upconversion) as a result of
      triplet-triplet annihilation. 

PMID- 23869826
TI  - Reliability of direct and indirect clinical attachment level measurements.
AB  - AIMS: To investigate the influence of subject-, tooth- and site-level
      characteristics on intra-examiner reproducibility of direct and indirect clinical
      attachment level (CALDIR and CALIND ) recordings, and to quantify the impact of
      less-than-perfect reliability on our ability to assess periodontitis progression.
      MATERIALS AND METHODS: Within a 1-week interval, a single examiner performed
      duplicate probing depth (PD), CALDIR and gingival recession (GR) recordings in
      six sites of all teeth present in 148 periodontitis patients. CALIND was
      calculated on the basis of the PD and GR. RESULTS: Agreement was observed in 65%,
      62%, 69% and 84% of the duplicate CALDIR , CALIND , PD and GR recordings,
      respectively, and >95% of the differences were within +/-1 mm. This study
      identified multiple predictors for CAL measurement errors >=1 mm, including tooth
      and site location, presence of supra- and subgingival calculus, bleeding on
      probing and suppuration. Measurement errors were more likely in patients
      diagnosed with "extensive" rather than "less extensive" periodontitis. In over
      half of the patients, measurement error frequencies were too high to allow for
      detection of possible CAL changes >=2 mm with a false-positive rate <=5%.
      Detection of CAL changes with low false-positives was more likely using
      recordings obtained by the direct method. CONCLUSIONS: From a measurement error
      point of view, CALDIR recordings are preferable over CALIND .

PMID- 23869827
TI  - [Endothelial dysfunction in pregnancies with chronic hypertension].
AB  - AIM OF THE STUDY: To establish endothelial activation markers which could uncover
      endothelial damage during hysiological pregnancy and pregnacies with chronic
      hypertension. SETTINGS: Department of Hemato-oncology, Obstetrics and Gynecology
      and Department of Medical Genetics and Fetal Medicine Medical Faculty of Palacky
      University Olomouc, Department of Obstetrics and Gynecology Medical Faculty
      Ostrava. METHODS: We examined 298 pregnant women with a physiological pregnancy.
      Venous blood samples were collected from the women in both arms at the beginning
      of the pregnancy, a second sample was collected in the interval 24-28 weeks
      gestation, the third sample was colected about the 36 weeks of gestation.
      Parameters were examined using methods: t-PA - ELISA, PAI-1 - ELISA, vWF - EIA,
      ePCR - ELISA, MMP-2,9 - ELISA with fluorogenic detection, TIMP-2 - ELISA,
      endothelial microparticles - flow cytometry. RESULTS: In accordance with the
      literature, we have observed in our study significantly increased endothelial
      activatition in hypertensive pregnancies compared with women with physiological
      pregnancy, as evidenced by significant increases in vWF activity and antigen,
      thrombomodulin and PAI-1 in all trimesters. In the other investigated parameters
      statistically significant changes were not observed. CONCLUSION: We have found
      significant signs of endothelial dysfunction in the group of women with pre
      existing hypertension, a wide range of parameters examined markers indicating an
      significantly increased endothelial activation pregnant women with pre-existing
      hypertension, confirming the need for strict follow-up of pregnant women with
      hypertensive disease.

PMID- 23869828
TI  - [The influence of warmed infusion during C-section on the mother and child--a
      pilot randomised prospective study].
AB  - AIM OF THE STUDY: To evaluate the influence of warmed infusions on the mothers
      and newborns well-being after C-section. DESIGN: Prospective randomized study.
      SETTING: Dept. of Anaesthesiology, Resuscitation and Intensive Care Medicine,
      Dept. of Obstetrics and Gynaecology, Faculty of Medicine and Dentistry Palacky
      University and University Hospital Olomouc. METHODS: Prospective randomized study
      including 29 pregnant women between 38th and 42nd week of pregnancy, that were
      indicated to elective caesarian section (SC) and from all of which the fetal
      distress was excluded. The women were randomized into four groups according to
      the temperature of applied infusion solution - colloids and afterwards
      crystalloids (pre-heated and non pre-heated), and according to the type of
      anaesthesia (general or SAB). These values were monitored in perioperative
      period: body temperature, differences of hemoglobin and hematocrit levels, tremor
      and pain level after the operation. In newborns the acid-base balance parameters
      and Apgar score were monitored. RESULTS: The study is still going on, however up
      to now some of the results suggest that usage of pre-heated infusion solutions is
      effective both for mother and child in increasing of their comfort in the
      perioperative period. In the group of actively heated mothers we have noticed:
      lower perioperative blood loss - differences in haemoglobin levels were 8 g/l
      compared to 15 g/l in the group of non heated mothers. The umbilical cord blood
      of the newborns whose mothers were not actively heated and were operated in
      subarachnoid anaesthesia had the lowest pO2 (0.9 kPa). The lowest level of
      umbilical cord blood lactate was noticed in the group of newborns whose mothers
      underwent the surgery under general anaesthesia and were actively heated.
      CONCLUSION: Up to now results suggest that the heating of mothers during the SC
      lowers the loss of body temperature, blood loss, and perception of pain by the
      mother. In combination with general anaesthesia it increases pO2 and lowers the
      levels of lactate in umbilical arteria in the newborns.

PMID- 23869829
TI  - [Gynaecological surgery of Jehovah's Witnesses].
AB  - OBJECTIVE: To present experience with surgical treatment of various
      gynaecological diseases in patients belonging to the Church of Jehova's Witness.
      DESIGNE: Retrospective study. SETTING: Department of Obstetrics and Gynaecology,
      Palacky University Olomouc, Institute of Health Care Studies, Faculty of Humanity
      Studies, Thomas Bata University, Zlin. METHODS AND RESULTS: The study included 24
      patients belonging to the Church of Jehova's Witness who reject blood tranfusion.
      The operations in these patients were performed for malignant as well as
      nonmalignant gynaecological disorders which could not be treated by conservative
      therapeutic procedures. The operation records were analysed and evaluated
      according to a set of criteria including the type of surgical procedure,
      estimated amount of blood loss, postoperative complications and the outcome of
      surgical treatment. CONCLUSION: Jehovas's Witnesses represent a risk group of
      patients considering their refusal of blood transfusion. The indication for the
      operation and its performing is responsible decision which always inherits a
      certain degrese of risk. On the other hand, when adhering to the principles of
      bloodless surgery, the therapeutic results are very good and in the properly
      indicated cases the scope of risk is acceptable.

PMID- 23869830
TI  - [The incidence of latent asymptomatic celiac disease in women with decreased
      fertility].
AB  - OBJECTIVE: To determine whether patients with recurrent spontaneous abortions and
      IVF suffer from latent celiac disease. DESIGN: Perspective study. SETTINGS:
      Department of Gynecology and Obstetrics and Faculty Hospital, Charles University,
      Pilsen. MATERIAL AND METHODS: Sera from 442 infertile patients aged 23-47 years
      and 86 healthy fertile controls aged 22-38 years were examined by commercial
      ELISA sets for the presence (absence) of antibodies against gliadin IgG, IgA and
      tissue transglutaminase in IgG and IgA. RESULTS: We found a statistically
      significant difference between the control group and patients with decreased
      fertility. They have a positive values in anti-tissue transglutaminase IgA (p =
      0.0096). Frequent, very low positive reaction of antigliadin IgG was also found
      in the control group of women. CONCLUSION: Patients with unexplained repeated
      miscarriages and repeated unsuccessful IVF with IgA positive tissue
      transglutaminase have new complement of other tests for autoimmunity and
      examination of a total IgA, and gastroenterological examination. Eleven patients
      with significant positive anti-tissue transglutaminase IgA were successfully
      conceived only under strict gluten-free diet.

PMID- 23869831
TI  - [Persistence of the treatment of overactive bladderin Czech Republic].
AB  - INTRODUCTION: Overactive bladder is chronic disease with high prevalence rate (9
      42%). This syndrome requires longterm therapy but the persistence of this
      treatment in comparison with other chronic diseases as diabetes, hypertension,
      osteoporosis etc. is low. Accorging many studies the persistence variability is
      high and could be influenced by regional circumstanses. We desided to analyze
      real situation in parasympatolytics persitance in two years period in Czech
      Republic based on registry of health insurance company. METHODS: We analyzed data
      between 2009 and 2010 of all clients of health insurance company where they
      fullfil their prescribtion. We analyzed the persistence in one year period in
      different periods of the year and within one year. RESULTS: In comparison of the
      same period between those two year there was a trend of increase of prescription
      but it was not significant: 1306(SD 56.3) vs 1410 (SD 68.1) - p = 0.056.
      Prescription of the treatment after one year was only 18.5%(min. 16.8 - max.
      20.4, SD 1.56). Major drop-out was in first 3-month period where renewed their
      prescription only 25.9% of the patients. CONCLUSION: This one of the first study
      analyzing the parasympatolytics prescription persistence based on registry of
      health insurence company. The persistence in Czech Republic was low but withing
      the range of international data. Those result should be used as a reference data
      for comparison of the effect of varius strategies influencing the overactive
      bladder treatment.

PMID- 23869832
TI  - [Radiotherapy in vulvar cancer treatment].
AB  - OBJECTIVE: To provide an actual review of radiotherapy in the treatment of vulvar
      carcinoma. DESIGN: A review article. SETTING: Department of Oncology and
      Radiotherapy, University Hospital in Hradec Kralove. METHODS: A review article
      evaluating the application of ionizing radiation in the treatment of early and
      advanced vulvar carcinoma, based on the most significant previously published
      studies. CONCLUSION: Postoperative groin irradiation in patients with positive
      groin lymph-nodes improves local control, time to progression, and overall
      survival; especially in 2 positive nodes and in N2/3 initial findings. In case of
      positive inguinal nodes, radiotherapy of both groins and at least lower pelvic
      iliac node-chains should follow. Adjuvant irradiation of the primary remains
      controversial, except for positive resection margins where radiotherapy improves
      overall survival. Concurrent chemoradiotherapy seems to be appropriate primary
      treatment of advanced vulvar carcinomas, in attempt to avoid mutilating
      intervention or exenteration. Chemoradiation should be followed by subsequent
      surgery, including potential groin dissection in case of lymph-node involvement.
      Definitive chemoradiotherapy is of limited evidence, and radical dose escalation
      to the gross tumor is essential for its implementation. Modern radiotherapy
      techniques, especially with intensity modulation, are convenient for dose
      escalation.

PMID- 23869833
TI  - [Expression of carbonic anhydrase IX in the breast carcinomas].
AB  - OBJECTIVE: Carbonic anhydrase IX (CA IX) is one indicator of hypoxia in the tumor
      and its expression is associated with more aggressive forms of breast cancer. The
      aim of this study is to point out its own set of correlation between CA IX
      expression and selected morphological and biological indicators. TYPE OF STUDY:
      Cohort prospective study. SETTING: Department of Pathology of Slovak Medical
      University and St. Elisabeth Cancer Institute, Bratislava, Slovak Republic.
      METHODS: These were 145 cases of breast cancer aged 25 to 85 years (median 59
      years) from the Register of the Institute of Pathology and Slovak Medical
      University and St. Elisabeth Cancer Institute in Bratislava for the period 1. 9.
      2012 to 28. 2. 2013. In all cases were examined CA IX, estrogen receptor (ER),
      progesterone receptor (PR), HER2, p53 and Ki67 by immunohistochemistry. Typing,
      grading and staging of the disease were evaluated according to the classification
      systems currently in place. RESULTS: CA IX expression was demonstrated in 51
      cases (35.2%). CA IX positivity correlated with the degree of differentiation (p
      = 0.0001), with ER status (p <0.0001) and PR (p <0.01) and HER2 (p <0.01) and
      proliferative activity as measured by Ki67 (p <0.001). HER2-positive cancers and
      triple-negative cancers were more frequently associated with the expression of CA
      IX compared with luminal subtypes (p <0.0001). The state of CA IX and age range
      of the tumor - pT and lymph node status - pN and p53 have not been shown
      statistically significant correlations. CONCLUSION: CA IX examination in breast
      cancer provides valuable information on the state of hypoxia in the tumor,
      thereby supplementing view of prognosis of the disease.

PMID- 23869834
TI  - [Psychosocial climate in maternity hospitals from the perspective of parturients
      II. Predictors of womens satisfaction with perinatal care in the Czech Republic].
AB  - OBJECTIVE: To identify the key determinants of parturients satisfaction with care
      provided in the Czech maternity hospitals and to draw up recommendation for good
      practice. DESIGN: Original study. SETTING: Department of Psychology, Faculty of
      Philosophy, Charles University, Prague. METHODS: Statistical analysis of data
      from the representative sample of Czech parturients (n = 1195) who gave birth
      from 2005 to 2012 in Czech maternity hospitals was conducted. Ordinal logistical
      regression (cumulative logit model) was used to identify predictors of womens
      satisfaction with intrapartum and postpartum care and their willingness to return
      and give birth in the same hospital as well as to recommend the hospital to
      others. The independent variables were the individual items of the KLI-P
      questionnaire measuring psychosocial climate in maternity hospitals and socio
      demographic and anamnestic characteristics of parturients. RESULTS: Among the
      most important determinants of parturients satisfaction with care at delivery
      unit were well-timed provision of information concerning a treatment plan (OR =
      2,79; p < 0,0001), privacy during the first stage of labour (OR = 2,81; p <
      0,0001), kind and helpful attitude of physicians (OR = 2,67; p < 0,0001) and
      confidence in physicians (OR = 2,68; p = 0,0001). Among the most important
      determinants of satisfaction with care at after-birth unit were well-timed
      provision of information concerning a treatment plan (OR = 2,25; p < 0,0001),
      active breastfeeding support (OR = 2,19;p < 0,0001), availability of caregivers
      (OR = 2,16;p < 0,0001), multiparity (OR = 1,52; p = 0,0001), respect shownby
      staff employed in mother care (OR = 2,02; p = 0,0004) and kind and helpful
      attitude of staff employed in newborn care (OR = 1,86; p = 0,0005). When
      considering the future place of birth and recommendation of the hospital to
      others, women predominantly take into account the care provided at delivery unit.
      Intrapartal care evaluation was affected to a lesser degree by satisfaction with
      midwives as compared to satisfaction with physicians. CONCLUSION: Analyses of the
      most important predictors of satisfaction with perinatal care indicate the need
      for practice to focus on enhancing psychosocial competences (particularly
      communication skills) of health care providers, more active breastfeeding support
      and communication of consistent information (especially concerning newborn care)
      by caregivers at after-birth unit.

PMID- 23869835
TI  - [Intrahepatic cholestasis of pregnancy].
AB  - The review of intrahepatic cholestasis of pregnancy attempts to summarize the
      current knowledge of this disease by analysing available literary sources.
      Intrahepatic cholestasis of pregnancy is a disease that typically appears in the
      third trimester of pregnancy, sometimes already at the end of the second
      trimester of pregnancy. The main symptom of the disease is pruritus. In addition,
      the disease is characterized by increased levels of liver enzymes and bile acids.
      The symptoms of the disease disappear spontaneously after delivery. The disease
      is associated with high incidence of fetal distress, as well as with a high risk
      of premature labour. The most serious obstetric complication is antenatal sudden
      fetal death. Fetal complications are probably caused by elevated levels of bile
      acids. Therefore the aim of treatment should be to minimize negative effects of
      bile acids on the fetus, to prolong pregnancy and reduce maternal symptoms at the
      same time.

PMID- 23869836
TI  - [Determination of anti-Mullerian hormone in women].
AB  - Anti-Mullerian hormone (AMH) is a glycoprotein and belongs to the TGF-beta growth
      factors family. Our review describes the method of AMH determination in serum and
      follicular fluid. The reference values and changes in AMH levels during a womans
      life are also discussed. In addition, it is also presented the relationship
      between AMH, obesity, smoking and use of hormonal contraceptives. The focus of
      the work is the importance of the determination of AMH in clinical practice. In
      assisted reproduction has become its determination one of the tools to detect
      ovarian reserve. It helps not only predict reduced response to stimulation with
      gonadotropins but also the risk of the ovarian hyperstimulation syndrome.
      Benefits of the ovarian reserve detection using AMH serum levels are discussed in
      comparison with the antral follicle count (AFC) determined by ultrasound. Several
      clinical indications of AMH determination are mentioned in the next section.
      These are primarily the polycystic ovary syndrome (PCOS), which is a great
      challenge not only for the AMH testing, but there is an open space for further
      interdisciplinary cooperation. Endometriosis has no direct effect on ovarian
      reserve and AMH levels in serum. AMH is very sensitive tumor marker in the
      diagnostics and monitoring of ovarian granulosa cells tumors. Treatment of cancer
      disease burdens entire body, including healthy cells. Ovarian follicles are very
      sensitive to chemotherapy and radiation. AMH is a good predictor of ovarian
      reserve damage during radio- and chemotherapy.

PMID- 23869837
TI  - [Cervical cancer--possibilities of detection of human papillomavirus].
AB  - OBJECTIVE: To describe the possibility of detection of HPV DNA in cervical
      cancer. DESIGN: Review. SETTING: Institute of Molecular and Translational
      Medicine, Laboratory of Experimental Medicine, Palacky University and University
      Hospital Olomouc. METHODS: Human papillomavirus (HPV) is the cause of many
      cancers, especially cervical cancer. Current cervical cancer screening is based
      on cytological examination, which is followed by HPV DNA diagnostics only in
      cases with abnormal results of uncertain significance. Methods used for HPV
      detection are often based on PCR reaction followed by genotyping (complete or
      partial). HPV DNA diagnostics isn't currently included into the primary cervical
      cancer screening in the Czech Republic although it has higher sensitivity than
      cytology. CONCLUSION: Inclusion of HPV DNA testing into the primary cervical
      cancer screening would significantly increase its sensitivity and thus would help
      to reduce the morbidity and mortality of this disease in Czech population.

PMID- 23869838
TI  - [Antibiotic profylaxis in obstetrics].
AB  - Nosocomial infections increase health care costs significantly and they are a
      real threat for all hospitalised patients as well. Surgical procedures affect
      imunological integrity in patients and increase risk of contamination and
      subsequent incidence of surgical site infections (SSIs). Antibiotic profylaxis
      according to recent trials has been shown to be effective in reducing the risks
      of postoperative infectious complications particularly in women undergoing
      cesarean section, termination of pregnancy in I. and II. trimester and repair of
      extensive obstetric perineal injuries. Benefit of antibiotic profylaxis hasn t
      been proven in procedures such as amniocentesis, cerclage and manual uterine
      evacuation. The routine antibiotic administration isnt recommanded in cases of
      spontaneous preterm labour without membrane rupture due to an increased risk of
      worse long-term outcome of children.The authors present also recent studies
      regarding antivirotic profylaxis in pregnant women with hepatitis B and herpes
      genitalis recidivans. In the end of the article differences in antimicrobial
      administration in obese women and in patients with penicillin allergy anamnesis
      are mentioned.

PMID- 23869839
TI  - [Solitary fibrous tumor of endometrium--a case report].
AB  - OBJECTIVE: Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor. We
      present a case of SFT occurring in endometrium. DESIGN: Case report. SETTING:
      Department of Obstetrics and Gynecology, The Fingerland Department of Pathology,
      Medical Faculty of Charles University and Faculty Hospital Hradec Kralove. CASE
      REPORT: We report a case of 57 years old woman with SFT arising from the
      endometrium, which was diagnosed and treated at our department. Histological
      finding was supported by typical immunohistochemical profile of the tumor.
      Aggressive nature of the tumor wasnt showed. The patient underwent abdominal
      hysterectomy with bilateral adnexectomy and is followed up in regular periods.
      CONCLUSION: Occurence of solitary fibrous tumor (SFT) in the female genital tract
      is extremely rare. To the best of our knowledge, we report the first case of SFT
      occurring in endometrium. Because of potencial aggressive behaviour of the tumor
      complete surgical excision and close follow-up is highly recommended.

PMID- 23869840
TI  - [Peripartum cardiomyopathy after caesarean section--a case report].
AB  - OBJECTIVE: Peripartum cardiomyopathy is a rare form of cardiomyopathy of unclear
      etiology, which affects women in the last month of pregnancy or in the first five
      months after delivery. DESIGN: Case report. SETTING: Department of Obstetrics and
      Gynecology, Hospital Rychnov nad Kneznou. CASE REPORT: We report a case of 26
      years old woman with rapidly worsening shock state closely after caesarean
      section. As the cause of the shock was diagnosed heart failure due to peripartum
      cardiomyopathy. The myocardial function was normalized during the next 12 months
      despite previous dramatic course. CONCLUSION: Peripartum cardiomyopathy is a rare
      form of cardiomyopathy of unclear etiology, which affects women in the last month
      of pregnancy or in the first five months after delivery. Cardiomyopathy can have
      a rapid course and give rise to a cardiac arrest or toa permanent structural
      heart damage. We have to think about peripartum cardiomyopathy in women with
      symptoms of heart failure as in our case report. The tratment requires
      interdisciplinary cooperation.

PMID- 23869843
TI  - Linking autism measures with the ICF-CY: functionality beyond the borders of
      diagnosis and interrater agreement issues.
AB  - PURPOSE: This study aims to: (1) link measurements used in the diagnosis of
      children with autism spectrum disorders (ASDs) with the International
      Classification of Functioning, Disability and Health - Children and Youth Version
      (ICF-CY) and (2) analyse issues relating with interrater agreement within this
      process. METHOD: Three instruments for ASD diagnosis were linked with the ICF-CY
      using deductive content analysis. RESULTS: Correspondences between items' content
      and ICF-CY dimensions were identified for all ICF-CY components, except for
      environmental factors. Interrater agreement varied with the content of the units
      analyzed. CONCLUSION: The linkage between the ICF-CY and the analyzed measures
      provides a way to document assessment-intervention outcomes using a common
      language, as well as to integrate diagnostic and functional data. Diagnostic
      measurements provide functional information beyond the diagnostic criteria
      defined for autism. A functional perspective is added to diagnostic outcomes,
      thus better informing educational and rehabilitation practices for children with
      ASD.

PMID- 23869842
TI  - Prestroke factors associated with poststroke mortality and recovery in older
      women in the Women's Health Initiative.
AB  - OBJECTIVES: To examine prestroke lifestyle factors associated with poststroke
      mortality and recovery in older women. DESIGN: Longitudinal prospective cohort
      study. SETTING: The Women's Health Initiative (WHI, clinical trials and
      observational study), 40 clinical centers in the United States. PARTICIPANTS: WHI
      participants, women aged 50 to 79, who were stroke-free at baseline (1993/98),
      with incident stroke before 2005. MEASUREMENTS: Participants were followed for
      mortality through 2010. Prestroke characteristics were from the last examination
      before the stroke event. Annual follow-up for clinical events ascertained
      hospitalization for stroke that was subsequently physician adjudicated with
      medical records. Multivariable regression models were used to analyze factors
      associated with poststroke mortality and poststroke recovery at hospital
      discharge (poststroke Glasgow score), adjusting for stroke type. RESULTS: Of
      3,173 women with incident stroke, 1,111 (35%) died. Individuals who were
      overweight or obese before stroke had lower poststroke mortality than those who
      were normal weight (obese: hazard ratio (HR) = 0.69, 95% confidence interval (CI)
      = 0.53-0.88; overweight: HR = 0.72, 95% CI = 0.58-0.90); individuals who were
      underweight before stroke had nonsignificantly greater poststroke mortality (HR =
      2.02, 95% CI = 0.98-4.16, P = .06). Other prestroke factors associated with
      poststroke mortality included diabetes mellitus (HR = 1.28, 95% CI = 1.01-1.64),
      current smoking (vs nonsmoker, HR = 2.13, 95% CI = 1.53-3.00), physical
      inactivity (vs >150 min of exercise per week, HR = 1.39, 95% CI = 1.09-1.78), and
      lowest physical function quartile (vs highest, HR = 1.54, 95% CI = 1.18-2.02).
      Prestroke diabetes mellitus was associated with lower odds of good recovery after
      stroke (odds ratio (OR) = 0.60, 95% CI = 0.44-0.82). Current hormone use before
      stroke was associated with greater odds of moderate than of severe disability
      after stroke (OR = 1.29, 95% CI = 1.00-1.66). CONCLUSION: Potentially modifiable
      factors before stroke, including smoking, diabetes mellitus, and being
      underweight, were associated with greater poststroke mortality in older women.
      Being overweight or obese and physical activity before stroke were associated
      with lower poststroke mortality in older women.

PMID- 23869841
TI  - Human immune system development and survival of non-obese diabetic (NOD)-scid
      IL2rgamma(null) (NSG) mice engrafted with human thymus and autologous
      haematopoietic stem cells.
AB  - Immunodeficient mice bearing targeted mutations in the IL2rg gene and engrafted
      with human immune systems are effective tools for the study of human
      haematopoiesis, immunity, infectious disease and transplantation biology. The
      most robust human immune model is generated by implantation of human fetal thymic
      and liver tissues in irradiated recipients followed by intravenous injection of
      autologous fetal liver haematopoietic stem cells [often referred to as the BLT
      (bone marrow, liver, thymus) model]. To evaluate the non-obese diabetic (NOD)
      scid IL2rgamma(null) (NSG)-BLT model, we have assessed various engraftment
      parameters and how these parameters influence the longevity of NSG-BLT mice. We
      observed that irradiation and subrenal capsule implantation of thymus/liver
      fragments was optimal for generating human immune systems. However, after 4
      months, a high number of NSG-BLT mice develop a fatal graft-versus-host disease
      (GVHD)-like syndrome, which correlates with the activation of human T cells and
      increased levels of human immunoglobulin (Ig). Onset of GVHD was not delayed in
      NSG mice lacking murine major histocompatibility complex (MHC) classes I or II
      and was not associated with a loss of human regulatory T cells or absence of
      intrathymic cells of mouse origin (mouse CD45(+) ). Our findings demonstrate that
      NSG-BLT mice develop robust human immune systems, but that the experimental
      window for these mice may be limited by the development of GVHD-like pathological
      changes. 

PMID- 23869844
TI  - Feasibility of endoscopic retrograde cholangiopancreatography-related procedures
      in hemodialysis patients.
AB  - BACKGROUND AND AIM: The opportunities of endoscopic retrograde
      cholangiopancreatography (ERCP)-related procedure for hemodialysis (HD) patients
      have been increasing recently. However, the complication rate of ERCPs in HD
      patients has not been evaluated sufficiently. We aimed to clarify the feasibility
      of ERCPs in HD patients. METHODS: We retrospectively reviewed 76 consecutive
      ERCPs for HD patients between January 2005 and December 2012 in one university
      hospital and three tertiary-care referral centers. Endoscopic sphincterotomy
      (EST) was performed in 21 HD patients. We evaluated the incidence and risk
      factors for complications of all ERCPs and EST in HD patients. RESULTS: The
      incidence of pancreatitis, cholangitis, and cardiopulmonary complications for
      ERCPs in HD patients was 7.9% (6/76), 1.3% (1/76), and 1.3% (1/76), respectively.
      The mortality rate was 2.6% (2/76), and it occurred after acute pancreatitis in
      one patient and pneumonia in the other patient. The incidence of hemorrhage and
      pancreatitis with EST was 19% (4/21) and 4.8% (1/21), respectively. The duration
      of HD was significantly longer in the patients with hemorrhage after EST than
      without (19.5 vs 6 years; P = 0.029). CONCLUSIONS: ERCP is feasible in HD
      patients. However, EST is not advisable because of the high hemorrhage rate,
      particularly for patients with a long duration of HD.

PMID- 23869845
TI  - Potential communicative acts in children with autism spectrum disorders.
AB  - OBJECTIVE: To describe potential communicative acts in a sample of 17 children
      with autism spectrum disorders who produced few to no intelligible words (mean
      age = 32.82 months). METHODS: Parents reported on children's potential
      communicative acts for 10 different communicative functions. A potential
      communicative act was defined as any behavior produced by an individual that may
      be interpreted by others to serve a communicative purpose. RESULTS: Significant
      associations were found between higher number of gesture types and increased
      scores on language comprehension, language expression, and non-verbal thinking
      measures. Relative to other types of potential communicative acts, parents
      reported that children used higher proportions of body movement. CONCLUSION:
      Number of body movement types was not related to child ability, while number of
      gesture types was related to receptive and expressive language. Findings
      underscore the link between language and gesture, and offer support for an
      ecological systems perspective of language learning.

PMID- 23869846
TI  - Genetic roadmap of the Arctic: plant dispersal highways, traffic barriers and
      capitals of diversity.
AB  - We provide the first comparative multispecies analysis of spatial genetic
      structure and diversity in the circumpolar Arctic using a common strategy for
      sampling and genetic analyses. We aimed to identify and explain potential general
      patterns of genetic discontinuity/connectivity and diversity, and to compare our
      findings with previously published hypotheses. We collected and analyzed 7707
      samples of 17 widespread arctic-alpine plant species for amplified fragment
      length polymorphisms (AFLPs). Genetic structure, diversity and distinctiveness
      were analyzed for each species, and extrapolated to cover the geographic range of
      each species. The resulting maps were overlaid to produce metamaps. The Arctic
      and Atlantic Oceans, the Greenlandic ice cap, the Urals, and lowland areas
      between southern mountain ranges and the Arctic were the strongest barriers
      against gene flow. Diversity was highest in Beringia and gradually decreased into
      formerly glaciated areas. The highest degrees of distinctiveness were observed in
      Siberia. We conclude that large-scale general patterns exist in the Arctic,
      shaped by the Pleistocene glaciations combined with long-standing physical
      barriers against gene flow. Beringia served as both refugium and source for
      interglacial (re)colonization, whereas areas further west in Siberia served as
      refugia, but less as sources for (re)colonization. 

PMID- 23869847
TI  - Reflecting on non-reflective action: an exploratory think-aloud study of self
      report habit measures.
AB  - OBJECTIVES: Within health psychology, habit - the tendency to enact action
      automatically as a learned response to contextual cues - is most commonly
      quantified using the 'Self-Report Habit Index', which assesses behavioural
      automaticity, or measures combining self-reported behaviour frequency and context
      stability. Yet, the use of self-report to capture habit has proven controversial.
      This study used 'think-aloud' methods to investigate problems experienced when
      completing these two measures. DESIGN: Cross-sectional survey with think-aloud
      study. METHODS: Twenty student participants narrated their thoughts while
      completing habit measures applied to four health-related behaviours (active
      commuting, unhealthy snacking, and one context-free and one context-specific
      variant of alcohol consumption). Data were coded using thematic analysis
      procedures. RESULTS: Problems were found in 10% of responses. Notable findings
      included participants lacking confidence in reporting automaticity, struggling to
      recall behaviour or cues, differing in interpretations of 'commuting', and
      misinterpreting items. CONCLUSIONS: While most responses were unproblematic, and
      further work is needed to investigate habit self-reports among larger and more
      diverse samples, findings nonetheless question the sensitivity of the measures,
      and the conceptualization of habit underpinning common applications of them. We
      offer suggestions to minimize these problems. Statement of contribution What is
      already known on this subject? Habit is most commonly measured within health
      psychology via the Self-Report Habit Index, or a combination of self-reported
      behaviour frequency and contextual stability. The suitability of self-report for
      capturing automatic processes has been questioned. What does this study add? This
      is the first study of how people interpret and respond to self-report habit
      measures. Results show the potential for errors in recalling automaticity, cues,
      and behaviours. We discuss practical and theoretical challenges to assessing
      habit in health behaviours.

PMID- 23869848
TI  - Developing a hierarchy of needs for Type 1 diabetes.
AB  - AIMS: The aim of this study was to use the concept of Maslow's hierarchy of needs
      and apply this to Type 1 diabetes. METHODS: Qualitative methods were employed
      using semi-structured interviews with 101 people from 13 countries. Grounded
      theory was used for data collection and analysis, with thematic analysis employed
      to identify the interviewees' needs. RESULTS: Sixteen needs were identified and
      links between these were mapped. Aligning these with Maslow's hierarchy allowed
      for a hierarchy to be developed for Type 1 diabetes with 'Policies',
      'Organization of health system', 'Insulin', 'Delivery of insulin', 'Control',
      'Healthcare workers' and 'Information and education' at the base, as they were
      needed for survival. Next came 'Community, family and peers' and changing roles
      for 'Healthcare workers' in their approach to care and delivering 'Information
      and education'. This enabled people to learn how to use 'Insulin', 'Delivery of
      insulin' and 'Control' flexibly. People's 'Experience' and 'Personality' then
      helped them 'Adapt' and 'Be open' about their diabetes, allowing for 'Acceptance'
      and viewing 'Diabetes as something positive'. CONCLUSIONS: Despite limitations,
      this work highlights that some needs are required for survival and others for
      well-being. Some are tangible as they can be directly provided, whereas others
      are intangible and cannot be provided directly by the health system. These
      results might be used for policy and practice in identifying needs that are met
      within a health system or what needs are lacking for the individual to then
      implement targeted interventions.

PMID- 23869849
TI  - A very special thank you!

PMID- 23869850
TI  - High performance liquid chromatographic determination of residual monomer
      released from heat-cured acrylic resin. An in vivo study.
AB  - PURPOSE: Heat-polymerized acrylic resins are used in dentistry for complete
      denture fabrication. Despite the polymerization method, conversion of monomer
      into polymer is often incomplete with free or unreacted residual monomer
      remaining in the polymerized resin. The aim of this study was to determine the
      amount of residual monomeric methyl methacrylate (MMA) leaching in the saliva of
      patients wearing complete dentures in their postinsertion period. MATERIALS AND
      METHODS: Thirty edentulous participants as first-time complete denture wearers
      (age 60 to 65 years) were selected. All the prostheses were fabricated using a
      similar standard technique with a heat-cured acrylic resin denture base material.
      Saliva samples were collected at time intervals of 1 hour, 1 day, and 3 days
      postdenture insertion. Participants were asked to discharge saliva every 30
      seconds into a pre-weighed screw-capped container for a 5-minute period. MMA
      levels were measured using high performance liquid chromatography. Data were
      analyzed by ANOVA and Tukey-HSD. RESULTS: The maximum concentration of monomer
      released into saliva peaked 1 day after insertion of the complete dentures. The
      mean (SD) MMA content was 0.04 +/- 0.01 (MUg/ml) 1 hour after insertion, and 0.3
      +/- 0.09 (MUg/ml), and 0.05 +/- 0.01 (MUg/ml) on the first and third days
      postinsertion, respectively. CONCLUSIONS: Although the released monomeric MMA was
      not at toxic levels, it could potentially sensitize complete denture patients or
      elicit an allergic reaction. The risk of the residual material as a primary
      irritant for a sensitizing reaction could be minimized by immersion of the
      denture in water for 24 hours before insertion.

PMID- 23869852
TI  - Electronic properties of a graphene device with peptide adsorption: insight from
      simulation.
AB  - In this work, to explain doping behavior of single-layer graphene upon
      HSSYWYAFNNKT (P1) and HSSAAAAFNNKT (P1-3A) adsorption in field-effect transistors
      (GFETs), we applied a combined computational approach, whereby peptide adsorption
      was modeled by molecular dynamics simulations, and the lowest energy
      configuration was confirmed by density functional theory calculations. On the
      basis of the resulting structures of the hybrid materials, electronic structure
      and transport calculations were investigated. We demonstrate that pi-pi stacking
      of the aromatic residues and proximate peptide backbone to the graphene surface
      in P1 have a role in the p-doping. These results are consistent with our
      experimental observation of the GFET's p-doping even after a 24-h annealing
      procedure. Upon substitution of three of the aromatic residues to Ala in (P1-3A),
      a considerable decrease from p-doping is observed experimentally, demonstrating n
      doping as compared to the nonadsorbed device, yet not explained based on the
      atomistic MD simulation structures. To gain a qualitative understanding of P1
      3A's adsorption over a longer simulation time, which may differ from aromatic
      amino acid residues' swift anchoring on the surface, we analyzed equilibrated
      coarse-grain simulations performed for 500 ns. Desorption of the Ala residues
      from the surface was shown computationally, which could in turn affect charge
      transfer, yet a full explanation of the mechanism of n-doping will require
      elucidation of differences between various aromatic residues as dependent on
      peptide composition, and inclusion of effects of the substrate and environment,
      to be considered in future work. 

PMID- 23869853
TI  - Determinative and confirmatory method for residues of tetracyclines in honey by
      LC-MS/MS.
AB  - A limited number of substances are authorised for the treatment of bees. Maximum
      residue limits (MRLs) are set for tetracyclines in several matrices, but not for
      honey. Nevertheless, tetracycline antibiotics may be used in order to prevent
      bacterial diseases and the loss of honey bee populations. In this study, a
      sensitive multi-residue LC-MS/MS method was developed and optimised for the
      quantitative and qualitative determination of tetracycline residues in honey.
      Homogenisation of samples under acidic conditions was performed and solid-phase
      extraction was carried out. The eluate was evaporated under nitrogen and
      dissolved in an aqueous methanol solution prior to filtration. A mobile phase
      composed of acetic acid-water and acetic acid-acetonitrile was used. Separation
      of tetracycline, oxytetracycline, chlortetracycline and doxytetracycline was
      achieved by using gradient elution on a C18 chromatography column. The analytical
      method was validated according to Commission Decision 2002/657/EC by the analysis
      of spiked samples around the recommended concentration of 20 MUg kg(-1) by EURL
      Guidance Paper, December 2007. A matrix effect was observed, so quantification
      was based on an external matrix calibration curve. Calculated decision limits
      (CCalpha) were lower than 10 MUg kg(-1) for all tetracyclines. Good linearity,
      repeatability and within-laboratory reproducibility were achieved.

PMID- 23869854
TI  - Let's face it: patient and parent perspectives on incorporating a Facebook group
      into a multidisciplinary weight management program.
AB  - BACKGROUND: Social media may have the potential to enhance weight management
      efforts. However, the acceptability of incorporating this entity into pediatrics
      is unknown. The objective of this project was to explore patients' and parents'
      perspectives about developing a Facebook group as a component of a pediatric
      weight management program. METHODS: Semistructured interviews were performed
      between September, 2011, and February, 2012, with patients and parents in a
      multidisciplinary weight management program. Interviews explored participants'
      perceptions of potential benefits, concerns, and preferences related to a program
      specific Facebook group. Transcripts were reviewed and themes identified. The
      study concluded when thematic saturation was achieved. RESULTS: Participants
      (n=32) were largely enthusiastic about the idea of a program-specific Facebook
      group for adolescents. Most preferred a secret group, where only participants
      would know of the group's existence or group members' identity. No parents
      expressed concern about security or privacy related to a program-specific
      Facebook group; one parent expressed concern about undesirable advertisements.
      Participants endorsed a variety of ideas for inclusion on the page, including
      weight loss tips, live chats with providers, quizzes, and an incentive system
      where participants could gain points for making healthy choices. Many parents
      requested a separate parent-focused page, an idea that was supported by the
      adolescents. CONCLUSIONS: This study suggests that participants perceive
      potential benefits from incorporating social media interventions into pediatric
      weight management efforts. Privacy and security issues do not appear to be major
      parental concerns. Future work should explore the impact of program-specific
      social media interventions on outcomes for patients in weight management
      programs.

PMID- 23869855
TI  - Mechanical properties of giant liposomes compressed between two parallel plates:
      impact of artificial actin shells.
AB  - The mechanical response of giant liposomes to compression between two parallel
      plates is investigated in the context of an artificial actin cortex adjacent to
      the inner leaflet of the bilayer. We found that nonlinear membrane theory
      neglecting the impact of bending sufficiently describes the mechanical response
      of liposomes consisting of fluid lipids to compression whereas the formation of
      an actin cortex or the use of gel-phase lipids generally leads to substantial
      stiffening of the shell. Giant vesicles are gently adsorbed on glassy surfaces
      and are compressed with tipless cantilevers using an atomic force microscope.
      Force-compression curves display a nonlinear response that allows us to determine
      the membrane tension sigma0 and the area compressibility modulus K(A) by
      computing the contour of the vesicle as a function of the compression depth. The
      values for KA of fluid membranes correspond well to what is known from micropipet
      suction experiments and computed from monitoring membrane undulations. The
      presence of a thick actin shell adjacent to the inner leaflet of the liposome
      membrane stiffens the system considerably, as mirrored in a significantly higher
      apparent area compressibility modulus.

PMID- 23869856
TI  - Effect of widespread agricultural chemical use on butterfly diversity across
      Turkish provinces.
AB  - Although agricultural intensification is thought to pose a significant threat to
      species, little is known about its role in driving biodiversity loss at regional
      scales. I assessed the effects of a major component of agricultural
      intensification, agricultural chemical use, and land-cover and climatic variables
      on butterfly diversity across 81 provinces in Turkey, where agriculture is
      practiced extensively but with varying degrees of intensity. I determined
      butterfly species presence in each province from data on known butterfly
      distributions and calculated agricultural chemical use as the proportion of
      agricultural households that use chemical fertilizers and pesticides. I used
      constrained correspondence analyses and regression-based multimodel inference to
      determine the effect of environmental variables on species composition and
      richness, respectively. The variation in butterfly species composition across the
      provinces was largely explained (78%) by the combination of agricultural chemical
      use, particularly pesticides, and climatic and land-cover variables. Although
      overall butterfly richness was primarily explained by climatic and land-cover
      variables, such as the area of natural vegetation cover, threatened butterfly
      richness and the relative number of threatened butterfly species decreased
      substantially as the proportion of agricultural households using pesticides
      increased. These findings suggest that widespread use of agricultural chemicals,
      or other components of agricultural intensification that may be collinear with
      pesticide use, pose an imminent threat to the biodiversity of Turkey.
      Accordingly, policies that mitigate agricultural intensification and promote low
      input farming practices are crucial for protecting threatened species from
      extinction in rapidly industrializing nations such as Turkey. Efectos del Uso
      Extensivo de Agroquimicos sobre la Diversidad de Mariposas en Provincias Turcas. 

PMID- 23869857
TI  - Refractive index sensing with subradiant modes: a framework to reduce losses in
      plasmonic nanostructures.
AB  - Plasmonic modes with long radiative lifetimes, subradiant modes, combine strong
      confinement of the electromagnetic energy at the nanoscale with a steep spectral
      dispersion, which makes them promising for biochemical sensors or immunoassays.
      Subradiant modes have three decay channels: Ohmic losses, their extrinsic
      coupling to radiation, and possibly their intrinsic dipole moment. In this work,
      the performance of subradiant modes for refractive index sensing is studied with
      a general analytical and numerical approach. We introduce a model for the impact
      that has different decay channels of subradiant modes on the spectral resolution
      and contrast. It is shown analytically and verified numerically that there exists
      an optimal value of the mode coupling for which the spectral dispersion of the
      resonance line shape is maximal. The intrinsic width of subradiant modes
      determines the value of the dispersion maximum and depends on the penetration of
      the electric field in the metallic nanostructure. A figure of merit, given by the
      ratio of the sensitivity to the intrinsic width, which are both intrinsic
      properties of subradiant modes, is introduced. This figure of merit can be
      directly calculated from the line shape in the far-field optical spectrum and
      accounts for the fact that both the spectral resolution and contrast determine
      the limit of detection. An expression for the intrinsic width of a plasmonic mode
      is derived and calculated from the line shape parameters and using perturbation
      theory. The method of analysis introduced in this work is illustrated for dolmen
      and heptamer nanostructures. Fano-resonant systems have the potential to act as
      very efficient refractive index sensing platforms compared to Lorentz-resonant
      systems, due to control of their radiative losses. This study paves the way
      toward sensitive nanoscale biochemical sensors and immunoassays with a low limit
      of detection and, in general, any nano-optical device where Ohmic losses limit
      the performance. 

PMID- 23869858
TI  - Role of the LysR-type transcriptional regulator PecT and DNA supercoiling in the
      thermoregulation of pel genes, the major virulence factors in Dickeya dadantii.
AB  - Bacteria are colonizers of various environments and host organisms, and they are
      often subjected to drastic temperature variations. Dickeya dadantii is a pathogen
      infecting a wide range of plant species. Soft rot, the visible symptom, is mainly
      due to the production of pectate lyases (Pels) that destroy plant cell walls. The
      production of Pels is controlled by a complex regulation system that responds to
      various stimuli, such as the presence of pectin, growth phase and temperature.
      Despite numerous regulatory studies, the thermoregulation mechanism of Pel
      production remains unexplained. Here, we show that PecT, a previously identified
      repressor, modulates pel gene expression in a temperature-dependent manner, and
      we demonstrate that PecT binding on pel promoters increases concomitantly with
      temperature. High temperatures relax the DNA in D. dadantii, and remarkably,
      artificial relaxation of DNA at low temperatures increases PecT binding to DNA.
      Deletion of pecT augmented the capacity of D. dadantii to initiate soft-rot
      symptoms at high temperatures. These results reveal that DNA topology and PecT
      act in concert to fine-tune D. dadantii virulence in response to temperature.
      This novel combination between DNA topology and a conventional transcriptional
      regulator extends our understanding of the thermoregulation mechanisms involved
      in bacterial virulence. 

PMID- 23869859
TI  - A few observations on metacontrast stimuli.
AB  - Metacontrast is a form of visual masking in which the target and mask are non
      overlapping. In metacontrast, the masking effect is typically largest when the
      mask is presented some time after the target. This is known as Type-B masking.
      The present report examines to what extent Type-B metacontrast masking can be
      explained based on the stimuli involved. The assumption is made that the
      visibility of the target is, at least in part, determined by the correlation
      between the amplitude spectrum of the target-and-mask combination and that of the
      target alone. It is found that the correlation is higher when the stimuli are
      presented at the same time relative to when they are presented at different
      times. This relationship follows from the stimuli alone. Thus, one would expect
      the masking to be weakest when the two stimuli are simultaneous. Type-B
      correlation functions, in which the largest reductions occur only when the mask
      is presented after the target, can be obtained by further assuming a temporal
      integration window with a rapid onset and a shallow decline. In agreement with
      psychophysical masking studies; the analyses yield functions that are most
      similar to Type-B masking for moderate mask intensities and become less Type-B
      like at higher mask intensities. The effects of dark adaptation and spatial
      separation of target and mask are also modeled. 

PMID- 23869860
TI  - Motive related positivity: decision-making during a prisoners' dilemma task.
AB  - The neural mechanisms underlying decision-making to cooperate or defect were
      investigated using event-related potentials during an iterated computer
      Prisoner's Dilemma task, adapted to induce working memory operation. Event
      related potentials from 64 leads of 22 participants were recorded during 90
      trials and averaged depending on the condition of cooperation and defect. The
      P200 component of the event-related potentials provided evidence for activation
      differences between cooperation and defect. Cooperation elicited significantly
      increased P200 activation at parieto-occipital leads, while defect activated
      primarily the prefrontal electrodes. Functional mapping using Low Resolution
      Electromagnetic Tomography indicated that in the 150-180 ms time window Brodmann
      areas 19 (precuneus) and 17 (lingual gyrus), exhibited increased activation
      during cooperation, while Brodmann area 6 (precentral gyrus) exhibited increased
      activation when participants defected. In conclusion, the current study provides
      evidence that cooperation and defect elicit different brain activation at
      specific loci and within specific time windows. 

PMID- 23869861
TI  - Regional connections of the mediodorsal thalamic nucleus in the rat.
AB  - Thalamic nuclei are classified as first- and higher-order relays. The first-order
      relays receive their driving afferents from ascending pathways and transmit
      messages to cortex that cortex has not seen before. The higher-order relays
      receive driver messages from layer-5 cortical cells for transmission from one
      cortical area to another. The present study used the retrograde tracer, fluoro
      gold, to define the afferents to the three regions of the mediodorsal thalamic
      nucleus, to distinguish which parts contain first- or higher-order relays. The
      results show that the main inputs to the medial region of the nucleus come from
      olfactory and visceral structures, those to the central region come from limbic
      structures and those to the lateral region come from motor centers of the central
      nervous system. The medial and central regions receive both modulatory (layer 6)
      and driver (layer 5) afferent inputs from the orbitofrontal and medial frontal
      areas of the prefrontal cortex whereas the lateral region receives no layer-5
      inputs from its cortical connections. Further, the inhibitory modulation of the
      mediodorsal thalamic nucleus shows regional differences. The medial region
      receives inhibitory afferents from the striatum (globus pallidus, caudate
      putamen), the lateral region from the substantia nigra pars reticulata and the
      zona incerta, and all segments of the mediodorsal thalamic nucleus receive
      inhibitory afferents from the thalamic reticular nucleus. The results of the
      present study show that each region of the mediodorsal thalamic nucleus has
      distinct afferent connections allowing each region of mediodorsal thalamic
      nucleus to be considered relatively independent subnuclei that may subserve
      independent functions. 

PMID- 23869862
TI  - Functional segregation in the left premotor cortex in language processing:
      evidence from fMRI.
AB  - Functional segregation has been revealed in the premotor cortex (PMC) and is
      related to motor and sensorimotor behaviors. Few data is available concerning the
      existence of similar segregation in the PMC during language processing. Here we
      correlated the roles of subregions of the left PMC in picture naming and
      articulation using functional magnetic resonance imaging (fMRI) and covert and
      overt picture naming in healthy volunteers. The results showed that the left
      dorsal PMC was extensively activated by covert picture naming, suggesting its
      recruitment in the naming network. The left ventral PMC was activated after
      comparison of overt vs. covert naming, suggesting its participation in
      articulation. These results may indicate that there is dorsal and ventral
      segregation of the left PMC during language processing. 

PMID- 23869863
TI  - Stress-induced modulation of nociceptive responses in the rat anterior cingulate
      cortex.
AB  - In the limbic system, the anterior cingulate cortex (ACCX) is one of the key
      areas involved in the close association between pain and emotion. However,
      neuronal changes in ACCX nociceptive responses after stress conditioning have not
      yet been quantitatively investigated. We investigated the modulation of
      nociceptive responses in the ACCX neurons following restraint stress in rats. The
      present study demonstrated that stress-conditioning enhanced excitatory
      nociceptive responses in the ACCX following tail stimuli in the mid-term (7
      days). Short-term (3 days) and long-term (21 days) of stress conditioning did not
      affect these responses significantly. Nociceptive responses evoked by other sites
      of the body (nose, back and four paws) stimulation were not changed by stress
      conditioning, indicating that neural information from the tail is important for
      emotional system modulation. It is suggested that the emotional/affective part of
      the pain sensation is strongly modified by stress through neuroplasticity in the
      ACCX. 

PMID- 23869864
TI  - Visual mismatch negativity in the "optimal" multi-feature paradigm.
AB  - To assess visual mismatch negativity (vMMN) elicited by several deviants in the
      optimal visual oddball paradigm with a short time, we developed a novel multi
      feature vMMN paradigm with five types of deviants integrated in a complex visual
      context of no more than 20 min. From time to time, the cross in the center of
      screen throughout the stimulus blocks became bigger or smaller unpredictably.
      Participants were instructed to ignore the peripheral standard and deviant
      stimuli on the left and right of the cross and press the left or the right button
      as quickly and accurately as possible when the size of the cross was changed.
      Five types of deviant visual stimuli were presented with the solid red rectangles
      as standard stimuli. Compared to the standard stimuli, each deviant stimulus
      elicited clearly negative deflection between 150-300 ms post stimulus, with
      larger amplitudes for orientation vMMN and smaller for size and duration vMMNs.
      The vMMNs were mainly implemented by the frontal lobe as well as the other cortex
      areas relevant to different visual features. This time-saving objective measure
      of vMMNs can be putatively used for studying visual discrimination ability in
      clinical patients unable to tolerate long-time-span tests. 

PMID- 23869865
TI  - Asynchrony of cerebral systems activated during word recognition: comparison of
      dyslexic and typical readers.
AB  - The aim of this study was to extend our understanding of the "asynchrony"
      phenomenon by examining the existence of several additional differences in brain
      activity. The differences which were investigated were the difference between the
      left and right hemisphere processing, the anterior and posterior areas processing
      and the differences between the different stages of information processing. These
      differences could account as an additional explanation for word decoding failure
      among individuals with dyslexia. The research utilized behavioral and
      electrophysiological (ERP - Event Related Potentials) measures in skilled and
      dyslexic university students. The subjects performed a lexical decision task
      presented in the visual and auditory modalities. The dyslexics exhibited a larger
      processing time interval between the activation of the P2 and P3 components,
      between the left and right hemisphere and between posterior and anterior regions
      of the cortex. Disharmony of the dyslexic brain is suggested as a possible
      explanation for the dyslexia phenomenon. 

PMID- 23869866
TI  - Electrophysiology and biochemical analysis of cyclocreatine uptake and effect in
      hippocampal slices.
AB  - In in vitro mouse hippocampal slices we investigated whether cyclocreatine is
      capable of entering brain cells independently of the creatine transporter and if
      it reproduces the neuroprotective effect of creatine. Our study shows that
      cyclocreatine does not increase the creatine content, but is taken up as such and
      then phosphorylated to phosphocyclocreatine. This uptake is largely blocked by
      inactivation of the creatine transporter, however some cyclocreatine is taken up
      and posphorylated even after such inactivation. Thus, cyclocreatine sets up a
      cyclocreatine/phosphocyclocreatine system in the brain independently of the
      creatine transporter. Cyclocreatine did not delay the disappearance of the evoked
      synaptic potentials during anoxia in hippocampal slices, unlike creatine which
      exerts a neuroprotective effect. 

PMID- 23869867
TI  - Application of proton-transfer-reaction-mass-spectrometry for Indoor Air Quality
      research.
AB  - In the field of Indoor Air Quality research, the measurement of volatile organic
      compounds (VOCs) demands instruments that are rapid, mobile, robust, highly
      sensitive and allow for simultaneous monitoring of multiple compounds. These
      instruments should also compensate for possible interferences from permanent
      gases and air humidity. Proton-transfer-reaction-mass-spectrometry (PTR-MS) has
      proved to be a valuable and promising technique that fits the mentioned
      requirements for a suitable online measuring device. In this study, five
      exemplary applications of PTR-MS are described: (i) release of paint additives
      during drying process, (ii) emission of VOCs from active hardcopy devices, (iii)
      reference material evaluation, (iv) diffusion studies, and (v) emission testing
      of building products. The examples are selected to illustrate possibilities and
      limitations of the PTR technique in this field of research. The quadruple-based
      PTR-QMS was able to determine the emission characteristics during the
      experiments, especially in case of depleting emission sources (e.g., reference
      material). This allows for chemometrical analysis of the measured release
      patterns and detection of underlying processes. However, PTR-QMS reaches a
      functional limit in case of compound identification. If identification of VOCs is
      necessary, the measurements need to be accompanied by GC/MS analytics or a PTR
      instrument with higher mass-resolution (e.g., PTR-TOF-MS). 

PMID- 23869868
TI  - Chemokine receptor CXCR2 is transactivated by p53 and induces p38-mediated
      cellular senescence in response to DNA damage.
AB  - Mammalian cells may undergo permanent growth arrest/senescence when they incur
      excessive DNA damage. As a key player during DNA damage response (DDR), p53
      transactivates an array of target genes that are involved in various cellular
      processes including the induction of cellular senescence. Chemokine receptor
      CXCR2 was previously reported to mediate replicative and oncogene-induced
      senescence in a DDR and p53-dependent manner. Here, we report that CXCR2 is
      upregulated in various types of cells in response to genotoxic or oxidative
      stress. Unexpectedly, we found that the upregulation of CXCR2 depends on the
      function of p53. Like other p53 target genes such as p21, CXCR2 is transactivated
      by p53. We identified a p53-binding site in the CXCR2 promoter that responds to
      changes in p53 functional status. Thus, CXCR2 may act downstream of p53. While
      the senescence-associated secretory phenotype (SASP) exhibits a kinetics that is
      distinct from that of CXCR2 expression and does not require p53, it reinforces
      senescence. We further showed that the cellular senescence caused by CXCR2
      upregulation is mediated by p38 activation. Our results thus demonstrate CXCR2 as
      a critical mediator of cellular senescence downstream of p53 in response to DNA
      damage. 

PMID- 23869869
TI  - Paediatric estimated average glucose in children with Type 1 diabetes.
AB  - AIM: Estimated average glucose has been used to transform HbA1c into a glucose
      measure that might better inform patients of their glycaemic control. The data
      set used to obtain the estimated average glucose equation was derived in adults
      with Type 1 and Type 2 diabetes, along with normal healthy control subjects, and
      requires testing in children. METHODS: This was a cross-sectional study of 234
      children and young people (106 male) with Type 1 diabetes aged 4.0-23.5 years who
      underwent continuous glucose monitoring over a 5-day period along with a measure
      of HbA1c . Regression analysis was used to determine estimated average glucose
      and agreement was assessed with the average glucose estimated from the Nathan
      equation: Nathan average glucose equation = 1.59 (HbA1c% ) - 2.59. RESULTS: Mean
      HbA1c was 76 mmol/mol (25.1) [9.1 (2.3)%] and mean continuous glucose monitoring
      tissue glucose was 10.4 (2.6) mmol/l. The relationship between continuous glucose
      monitoring tissue glucose and HbA1c was described by the paediatric equation:
      paediatric estimated average glucose = 0.49 (HbA1c %) + 5.95 (r = 0.45; P <
      0.001). The mean paediatric estimated average glucose was 10.4 (1.1) mmol/l
      compared with that from the Nathan average glucose equation of 11.9 (3.7) mmol/l
      (P < 0.001). Overall, the paediatric estimated average glucose was 2.7 mmol/l
      lower than the Nathan estimated average glucose, with a 95% limit of agreement of
      +/- 0.5 mmol/l. The agreement was very close with HbA1c values below 80 mmol/mol
      (9.5%). CONCLUSION: These data suggest that the Nathan estimated average glucose
      could be used in children and young people with Type 1 diabetes. Caution should
      still be exercised in the estimates derived for average glucose as the data set
      is skewed in both Nathan and paediatric average glucose estimates in opposite
      directions because of the differences in average HbA1c .

PMID- 23869870
TI  - Optimal immune defence in the light of variation in lifespan.
AB  - There is good evidence for costs to both the uses of immune defences and their
      development and maintenance. The optimal defence will be a balance of these costs
      with the risk of infection and the virulence of the disease. It is therefore
      clear that the life-history characteristics of both host and parasite will impact
      the optimal level of defence, and that this may in part explain the variation in
      immune defence against different pathogens and parasites. For instance, it has
      traditionally been suggested that long-lived hosts should invest in immune
      memory. Ecological evolutionary theory can be used to examine in detail how
      different host characteristics will affect the optimal immune response that
      evolves. Here, we review theoretical studies on the impact of host lifespan on
      various immune defence characteristics including acquired immunity and highlight
      the importance of population-level epidemiological feedbacks on the outcome. In
      particular, we discuss when longer-lived hosts may invest less in acquired
      immunity and develop new theory to highlight the importance of the mechanism of
      host population regulation to the outcome. We finish by discussing where more
      theory is needed and how comparative and experimental studies may test the
      theory.

PMID- 23869871
TI  - Electron transfer by excited benzoquinone anions: slow rates for two-electron
      transitions.
AB  - Electron transfer (ET) rate constants from the lowest excited state of the
      radical anion of benzoquinone, BQ(-*)*, were measured in THF solution. Rate
      constants for bimolecular electron transfer reactions typically reach the
      diffusion-controlled limit when the free-energy change, DeltaG degrees , reaches 
      0.3 eV. The rate constants for ET from BQ(-*)* are one-to-two decades smaller at
      this energy and do not reach the diffusion-controlled limit until -DeltaG degrees
      is 1.5-2.0 eV. The rates are so slow probably because a second electron must
      also undergo a transition to make use of the energy of the excited state.
      Similarly, ET, from solvated electrons to neutral BQ to form the lowest excited
      state, is slow, while fast ET is observed at a higher excited state, which can be
      populated in a transition involving only one electron. A simple picture based on
      perturbation theory can roughly account for the control of electron transfer by
      the need for transition of a second electron. The picture also explains how extra
      driving force (-DeltaG degrees ) can restore fast rates of electron transfer. 

PMID- 23869872
TI  - Perspectives on hand function in girls and women with Rett syndrome.
AB  - OBJECTIVE: Rett syndrome is a rare neurodevelopmental disorder that is usually
      associated with a mutation on the X-linked MECP2 gene. Hand function is
      particularly affected and we discuss theoretical and practical perspectives for
      optimising hand function in Rett syndrome. METHODS: We reviewed the literature
      pertaining to hand function and stereotypies in Rett syndrome and developed a
      toolkit for their assessment and treatment. RESULTS: There is little published
      information on management of hand function in Rett syndrome. We suggest
      assessment and treatment strategies based on available literature, clinical
      experience and grounded in theories of motor control and motor learning.
      CONCLUSION: Additional studies are needed to determine the best treatments for
      hand function in Rett syndrome. Meanwhile, clinical needs can be addressed by
      supplementing the evidence base with an understanding of the complexities of Rett
      syndrome, clinical experience, environmental enrichment animal studies and
      theories of motor control and motor learning.

PMID- 23869873
TI  - Assessment of health-related quality of life and how it predicts the outcome of
      pegylated interferon and ribavirin therapy for chronic hepatitis C.
AB  - BACKGROUND AND AIM: Chronic infection with hepatitis C virus (HCV) decreases
      health-related quality of life (HRQOL). The present study was planned to
      investigate the impact of HRQOL of patients with chronic hepatitis C (CHC) on the
      outcomes of therapy with pegylated interferon and ribavirin (RBV), in addition to
      IL28B polymorphisms. METHODS: The present study enrolled 228 CHC patients and
      assessed their HRQOLs prospectively with the 36-item short-form health survey.
      RESULTS: The patients with CHC have lower physical HRQOL status than the general
      population (P = 0.037, the Z-test). The patients with advanced liver diseases
      exhibited further decreases in HRQOL (P = 0.036, Spearman's rank correlation
      coefficient). The score of total HRQOL was significantly lower in the group with
      sustained virological response (SVR) to the therapy with pegylated interferon and
      RBV than the non-SVR group (P = 0.031, the Mann-Whitney U-test), with
      significantly lower scores of mental component and its comprising subscales in
      the SVR group. Stepwise multivariate logistic regression analysis showed that low
      HRQOL score <= 400 points was significantly associated with SVR (odds ratio =
      2.4, P = 0.013), independently from high platelet counts, low HCV RNA, favorable
      single-nucleotide polymorphism type of IL28B, and HCV serotype 2. The patients
      with low HRQOL score will have significantly less decrease in HRQOL score by 4
      weeks of the treatment than those with high HRQOL score at baseline (P = 0.0045).
      CONCLUSION: HRQOL is one of the significant predictor of the outcomes of therapy
      with pegylated interferon and RBV independently from IL28B polymorphism.

PMID- 23869874
TI  - Shifting baselines and the extinction of the Caribbean monk seal.
AB  - The recent extinction of the Caribbean monk seal Monachus tropicalis has been
      considered an example of a human-caused extinction in the marine environment, and
      this species was considered a driver of the changes that have occurred in the
      structure of Caribbean coral reef ecosystems since colonial times. I searched
      archaeological records, historical data, and geographic names (used as a proxy of
      the presence of seals) and evaluated the use and quality of these data to
      conclude that since prehistoric times the Caribbean monk seal was always rare and
      vulnerable to human predation. This finding supports the hypothesis that in AD
      1500, the Caribbean monk seal persisted as a small fragmented population in which
      individuals were confined to small keys, banks, or isolated islands in the Gulf
      of Mexico and the Caribbean Sea. This hypothesis is contrary to the assumption
      that the species was widespread and abundant historically. The theory that the
      main driver of monk seal extinction was harvesting for its oil for use in the
      sugar cane industry of Jamaica during the 18th century is based primarily on
      anecdotal information and is overemphasized in the literature. An analysis of
      reported human encounters with this species indicates monk seal harvest was an
      occasional activity, rather than an ongoing enterprise. Nevertheless, given the
      rarity of this species and its restricted distribution, even small levels of
      hunting or specimen collecting must have contributed to its extinction, which was
      confirmed in the mid-20th century. Some sources had been overlooked or only
      partially reviewed, others misinterpreted, and a considerable amount of anecdotal
      information had been uncritically used. Critical examination of archaeological
      and historical records is required to infer accurate estimations of the
      historical abundance of a species. In reconstructing the past to address the
      shifting baseline syndrome, it is important to avoid selecting evidence to
      confirm modern prejudices.

PMID- 23869875
TI  - Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast
      cancer risk in postmenopausal Danish women.
AB  - Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome
      P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in
      estrogen metabolism and PCB metabolism, both of which may relate to breast cancer
      susceptibility. Polymorphisms in genes regulating these enzymes control
      efficiency. Our objective was to assess whether CYP1B1 and COMT gene
      polymorphisms modulate the effect of PCBs in breast cancer risk, among
      postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose
      tissue PCBs were independently associated with breast cancer risk. When assessing
      the independent effect of the COMT Val158Met polymorphism, we observed reduced
      risk for breast cancer amongst hormone replacement therapy using women who were
      homozygous carriers of the variant allele compared with those carrying the wild
      type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically
      significant interactions between any of the PCB groups and CYP1B1 or COMT
      polymorphisms on the risk of breast cancer. 

PMID- 23869876
TI  - Nanoporous poly(lactide) by olefin metathesis degradation.
AB  - We describe an approach to ordered nanoporous poly(lactide) that relies on self
      assembly of poly(butadiene)-poly(lactide) (PB-PLA) diblock copolymers followed by
      selective degradation of PB using olefin metathesis. The block copolymers were
      obtained by a combination of anionic and ring-opening transesterification
      polymerizations. The molar mass of each block was tailored to target materials
      with either a lamellar or cylindrical microphase-separated morphology.
      Orientation of these nanoscale domains was induced in thin films and monolithic
      samples through solvent annealing and mechanical deformation, respectively.
      Selective degradation of PB was achieved by immersing the samples in a solution
      of Grubbs first-generation catalyst in cyclohexane, a nonsolvent for PLA.
      Successful elimination of PB was confirmed by size-exclusion chromatography and
      (1)H NMR spectroscopy. Direct imaging of the resulting nanoporous PLA was
      obtained by scanning electron microscopy. 

PMID- 23869878
TI  - The leisure activity settings and experiences of youth with severe disabilities.
AB  - OBJECTIVE: The objective was to describe the leisure activity settings of youth
      with severe disabilities, the environmental qualities of these settings, and
      youths' experiences. METHODS: Fifteen youth using augmentative and alternative
      communication and 11 with complex continuing care needs took part in 54 leisure
      activity settings of their own choosing. Following their participation, they
      completed the Self-Reported Experiences of Activity Settings questionnaire and
      trained observers completed the Measure of Environmental Qualities of Activity
      Settings. RESULTS: Youths' selected activity settings provided relatively high
      opportunities for choice, interaction with adults, and social activities, and
      youth experienced relatively high levels of psychological engagement, social
      belonging, and control and choice. Youth primarily took part in activity settings
      that provided opportunities for competency/relatedness and involved others.
      CONCLUSION: Implications for future research and clinical practice include the
      importance of valuing passive recreational activities for the opportunities for
      challenge, choice, and social interaction they provide.

PMID- 23869879
TI  - Novel engineered systems for oral, mucosal and transdermal drug delivery.
AB  - Technological advances in drug discovery have resulted in increasing number of
      molecules including proteins and peptides as drug candidates. However, how to
      deliver drugs with satisfactory therapeutic effect, minimal side effects and
      increased patient compliance is a question posted before researchers, especially
      for those drugs with poor solubility, large molecular weight or instability.
      Microfabrication technology, polymer science and bioconjugate chemistry combine
      to address these problems and generate a number of novel engineered drug delivery
      systems. Injection routes usually have poor patient compliance due to their
      invasive nature and potential safety concerns over needle reuse. The alternative
      non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal,
      rectal, vaginal), and transdermal drug delivery have thus attracted many
      attentions. Here, we review the applications of the novel engineered systems for
      oral, mucosal and transdermal drug delivery.

PMID- 23869880
TI  - Distinct localization of the complement C5b-9 complex on Gram-positive bacteria.
AB  - The plasma proteins of the complement system fulfil important immune defence
      functions, including opsonization of bacteria for phagocytosis, generation of
      chemo-attractants and direct bacterial killing via the Membrane Attack Complex
      (MAC or C5b-9). The MAC is comprised of C5b, C6, C7, C8, and multiple copies of
      C9 that generate lytic pores in cellular membranes. Gram-positive bacteria are
      protected from MAC-dependent lysis by their thick peptidoglycan layer.
      Paradoxically, several Gram-positive pathogens secrete small proteins that
      inhibit C5b-9 formation. In this study, we found that complement activation on
      Gram-positive bacteria in serum results in specific surface deposition of C5b-9
      complexes. Immunoblotting revealed that C9 occurs in both monomeric and polymeric
      (SDS-stable) forms, indicating the presence of ring-structured C5b-9.
      Surprisingly, confocal microscopy demonstrated that C5b-9 deposition occurs at
      specialized regions on the bacterial cell. On Streptococcus pyogenes, C5b-9
      deposits near the division septum whereas on Bacillus subtilis the complex is
      located at the poles. This is in contrast to C3b deposition, which occurs
      randomly on the bacterial surface. Altogether, these results show a previously
      unrecognized interaction between the C5b-9 complex and Gram-positive bacteria,
      which might ultimately lead to a new model of MAC assembly and functioning.

PMID- 23869881
TI  - Fine structure of the Plasmodia and Myxospore of Ellipsomyxa gobioides n. sp.
      (Myxozoa) found in the gallbladder of Gobioides broussonnetii (Teleostei:
      Gobiidae) from the lower Amazon river.
AB  - A fish infecting myxosporean Ellipsomyxa gobioides n. sp. is described in the
      gallbladder of the Amazonian dragon fish Gobioides broussonnetii. Irregular
      disporous plasmodia (up to ~30 MUm in diameter) with long branched and
      anastomosed pseudopodia were found attached to the gallbladder wall. Mature
      ellipsoid myxospores occurring floating in the bile measured 6.8 (6.5-7.0) MUm (n
      = 30) long, 7.2 (6.9-7.5) MUm (n = 15) wide, and 13.1 (12.8-13.5) (n = 25) thick.
      They had smooth thin valves elongated in the direction perpendicular to the plane
      of the straight central transverse sutural line. The two ellipsoidal polar
      capsules (PC) opened some distance from the sutural line on opposite sides, each
      measuring 4.6 (4.3-4.8) MUm (n = 15) long and 2.5 (2.1-2.7) MUm (n = 20) wide.
      Distance between PC 3.5 (3.1-3.8) MUm (n = 15) in apical view. The polar filament
      was isofilar and consisted of a single coil with five or six turns. The objective
      of this study was to characterize this new species based on its morphological
      differences from the three previously described species. This is the first
      reported species of genus Ellipsomyxa from among the South American fauna. 

PMID- 23869882
TI  - Solubility of lead and copper in biochar-amended small arms range soils:
      influence of soil organic carbon and pH.
AB  - Biochar is often considered a strong heavy metal stabilizing agent. However,
      biochar in some cases had no effects on, or increased the soluble concentrations
      of, heavy metals in soil. The objective of this study was to determine the
      factors causing some biochars to stabilize and others to dissolve heavy metals in
      soil. Seven small arms range soils with known total organic carbon (TOC), cation
      exchange capacity, pH, and total Pb and Cu contents were first screened for
      soluble Pb and Cu concentrations. Over 2 weeks successive equilibrations using
      weak acid (pH 4.5 sulfuric acid) and acetate buffer (0.1 M at pH 4.9), Alaska
      soil containing disproportionately high (31.6%) TOC had nearly 100% residual
      (insoluble) Pb and Cu. This soil was then compared with sandy soils from Maryland
      containing significantly lower (0.5-2.0%) TOC in the presence of 10 wt % (i)
      plant biochar activated to increase the surface-bound carboxyl and phosphate
      ligands (PS450A), (ii) manure biochar enriched with soluble P (BL700), and (iii)
      unactivated plant biochars produced at 350  degrees C (CH350) and 700  degrees C
      (CH500) and by flash carbonization (corn). In weak acid, the pH was set by soil
      and biochar, and the biochars increasingly stabilized Pb with repeated
      extractions. In pH 4.9 acetate buffer, PS450A and BL700 stabilized Pb, and only
      PS450A stabilized Cu. Surface ligands of PS450A likely complexed and stabilized
      Pb and Cu even under acidic pH in the presence of competing acetate ligand.
      Oppositely, unactivated plant biochars (CH350, CH500, and corn) mobilized Pb and
      Cu in sandy soils; the putative mechanism is the formation of soluble complexes
      with biochar-borne dissolved organic carbon. In summary, unactivated plant
      biochars can inadvertently increase dissolved Pb and Cu concentrations of sandy,
      low TOC soils when used to stabilize other contaminants.

PMID- 23869883
TI  - Novel DEPDC5 mutations causing familial focal epilepsy with variable foci
      identified.

PMID- 23869884
TI  - L-arginine in combination with sildenafil potentiates the attenuation of hypoxic
      pulmonary hypertension in rats.
AB  - Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary
      prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels
      correlates with concentration of L-arginine as well as activity of
      phosphodiesterase-5 enzyme (PDE-5). We tested a hypothesis whether a combination
      of L-arginine and PDE-5 inhibitor sildenafil has an additive effect in reduction
      of the hypoxic pulmonary hypertension (HPH) in rats. Animals were exposed to
      chronic normobaric hypoxia for 3 weeks. In the AH group, rats were administered L
      arginine during chronic hypoxic exposure. In the SH group, rats were administered
      sildenafil during chronic hypoxic exposure. In the SAH group, rats were treated
      by the combination of L-arginine as well as sildenafil during exposure to chronic
      hypoxia. Mean PAP, structural remodeling of peripheral pulmonary arterioles (%DL)
      and RV/LV+S ratio was significantly decreased in the SAH group compared to
      hypoxic controls even decreased compared to the AH and the SH groups in first two
      measured parameters. Plasmatic concentration of cGMP and NOx were significantly
      lower in the SAH group compared to hypoxic controls. We demonstrate that NO
      synthase substrate L-arginine and phosphodiesterase-5 inhibitor sildenafil
      administered in combination are more potent in attenuation of the HPH compared to
      a treatment by substances given alone. 

PMID- 23869885
TI  - Does aliskiren protect the kidney following ischemia reperfusion injury?
AB  - The effect of blocking the first and rate-limiting step in renin-angiotensin
      cascade on the renal function in ischemia reperfusion injury has not been
      previously investigated. We investigated the effect of aliskiren, the first
      approved direct oral renin inhibitor, on the alterations in renal functional
      parameters in this condition. Wistar rats underwent left renal ischemia for 40
      min. Group-1 received normal saline whereas Group-2 received aliskiren (30
      mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic
      and tubular functions and gene expression of neutrophil gelatinase-associated
      lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and
      left kidneys were measured five days following the IRI. Comparing Group-1 and
      Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/
      0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also
      higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs.
      0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2
      (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease
      in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In
      conclusions, the administration of aliskiren before and after IRI appears to have
      ameliorated the IRI effect on the total renal artery blood flow, fractional
      excretion of sodium and gene expression of both NGAL and PAI-1 indicating a
      renoprotective effects in IRI. 

PMID- 23869886
TI  - Short-term administration of alibernet red wine extract failed to affect blood
      pressure and to improve endothelial function in young normotensive and
      spontaneously hypertensive rats.
AB  - As wine polyphenols were shown to possess many positive effects in mammals,
      including improvement of vascular function, this study investigated the effect of
      the Slovak Alibernet red wine extract (AWE) on blood pressure and vascular
      function in young normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive
      (SHR) rats. Six weeks old, male, WKY and SHR were treated with AWE for three
      weeks at the dose of 24.2 mg/kg/day. Blood pressure (BP), determined by tail-cuff
      plethysmography, was significantly elevated in SHR vs. WKY and AWE failed to
      affect it. Lipid peroxidation was evaluated by determination of thiobarbituric
      acid-reactive substances. Vascular function was assessed in rings of the femoral
      artery using Mulvany-Halpern's myograph. Maximal endothelium-dependent
      acetylcholine (ACh)-induced relaxation was reduced in control SHR vs. WKY rats by
      approximately 9.3 %, which was associated with a significant decrease of its NO
      independent component. AWE failed to affect maximal ACh-induced relaxation, both
      its NO-dependent and independent components, compared to controls of the same
      genotype. AWE however reduced lipid peroxidation in the left ventricle of both
      WKY and SHR and in the liver of SHR. In conclusion, three-week administration of
      AWE failed to reduce BP and to improve endothelial function in the femoral
      arteries of both genotypes investigated. 

PMID- 23869887
TI  - Sphingosine-1-phosphate is a possible fibrogenic factor in gluteal muscle
      fibrosis.
AB  - Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles
      due to multiple etiologies. The main pathologic process is characterized by
      proliferation of fibroblasts and excessive accumulation of collagen in the
      extracellular matrix of the muscle. Sphingosine-1-phosphate (S1P) is a bioactive
      sphingolipid and has been reported to be associated with various fibrotic
      diseases. However, the role of S1P in GMC remains unknown. Here in this article,
      High-performance liquid chromatography and immunohistochemistry were applied to
      evaluate S1P localization and expression in clinical samples from patients with
      GMC, Quantitative real time PCR, Western blot, and enzyme-linked immunosorbent
      assay were used to explore the link between transforming growth factor-beta1 (TGF
      beta1), plasminogen activator inhibitor-1 (PAI-1) and S1P. The results showed
      that S1P was enhanced in contraction band (CB) tissues. Studies using the cell
      proliferation and transformation assay indicated that exogenous S1P stimulated CB
      fibroblast proliferation in a time-dependent manner and in higher concentration
      also in a dose-dependent manner. Furthermore, we demonstrated that S1P not only
      promoted collagen type I production, but also up-regulated mRNA and protein
      expression of transforming growth factor-beta1 and plasminogen activator
      inhibitor-1. These findings suggest that S1P may regulate increased synthesis of
      collagen and other fibrogenic factors, and significantly contributes to the
      process of gluteal muscle scarring in patients with GMC. 

PMID- 23869888
TI  - The effect of high-calorie meal consumption on oxidative stress and endothelial
      dysfunction in healthy male adults.
AB  - Several authors have reported the association of postprandial
      hypertriglyceridemia with oxidative stress, systemic inflammation and endothelial
      dysfunction. Our aim was to investigate the effect of high-calorie meal on blood
      markers of oxidative stress and endothelial dysfunction and the association of
      APOA5 -1131T/C and -250G/A hepatic lipase (HL) polymorphisms with postprandial
      triglyceride response. This study included 102 healthy male volunteers. All
      participants consumed a high-calorie meal (823 calories, 50 g fat, 28 g protein,
      60 g carbohydrates). Total cholesterol, triglycerides, HDL-cholesterol, LDL
      cholesterol, hsCRP, TAS and ICAM-1 were measured at fasting state and
      postprandially. APOA5 -1131T/C and -250G/A HL polymorphisms were also determined.
      Postprandial triglycerides were significantly increased (1.4 (1.1-2.1) vs. 2.4
      (1.9-3.3) mmol/l, P<0.001). Average triglyceride increase was 1.0+/-0.7 mmol/l
      (65 %). Concentration of triglycerides, HDL-cholesterol, LDL-cholesterol, TAS and
      ICAM-1 differed significantly between the fasting state and postprandial
      measurements (P<0.001). However, those differences were within the limits of
      analytical imprecision. Other parameters did not change 3 h after the meal.
      Triglycerides response did not differ respective to the APOA5 and HL
      polymorphisms. Family history of hypertension and acute myocardial infarction
      were associated with higher postprandial triglyceride concentrations.
      Postprandial hypertriglyceridemia is not associated with increased concentrations
      of hsCRP, TAS and ICAM-1. Furthermore, APOA5 -1131T/C and -250G/A HL
      polymorphisms are not associated with different postprandial triglyceride
      response. 

PMID- 23869889
TI  - Metabolic disturbances and defects in insulin secretion in rats with
      streptozotocin-nicotinamide-induced diabetes.
AB  - Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are
      often used in animal studies concerning various aspects of diabetes. In this
      experimental model, the severity of diabetes is different depending on doses of
      STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are
      not fully characterized. In our present study, metabolic changes and insulin
      secretion were investigated in rats with diabetes induced by administration of 60
      mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes
      induction, insulin, glucagon and some metabolic parameters were determined to
      evaluate the severity of diabetes. Moreover, insulin secretory capacity of
      pancreatic islets isolated from control and diabetic rats was compared. It was
      demonstrated that administration of 60 mg of STZ and 90 mg of NA per kg body
      weight induced relatively mild diabetes, since insulin, glucagon and other
      analyzed parameters were only slightly affected in diabetic rats compared with
      control animals. In vitro studies revealed that insulin secretory response was
      preserved in pancreatic islets of diabetic rats, however, was lower than in
      islets of control animals. This effect was observed in the presence of different
      stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately
      reduced in islets of diabetic rats compared with control islets. In the presence
      of leucine with glutamine, insulin secretion appeared to be also decreased in
      islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l
      glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was
      demonstrated that at a non-stimulatory glucose, pharmacological depolarization of
      plasma membrane with a concomitant activation of protein kinase C evoked
      significant rise in insulin release in islets of control and diabetic rats.
      However, in diabetic islets, this effect was attenuated. These results indicate
      that impairment in insulin secretion in pancreatic islets of rats with mild
      diabetes induced by STZ and NA results from both metabolic and nonmetabolic
      disturbances in these islets. 

PMID- 23869890
TI  - Effects of lower body positive pressure on cardiovascular responses during
      walking in elderly women.
AB  - This study was undertaken to investigate the effects of lower body positive
      pressure (LBPP) on cardiovascular responses during a 15-min walking trial in
      young (22.1+/-0.4 years) and elderly women (67.8+/-1.1 years). The application of
      20 mm Hg LBPP reduced ground reaction forces by 31.2+/-0.5 kgw in both groups. We
      hypothesized that cardiovascular responses to LBPP during walking were different
      between the young and elderly subjects. Applying 20 mm Hg of LBPP increased
      diastolic and mean blood pressure but not systolic blood pressure in both groups.
      LBPP-induced reduction in heart rate (HR) occurred more quickly in the young
      group compared to the elderly group (p<0.05). Applying LBPP also decreased double
      product (systolic blood pressure x HR) in both groups, suggesting that LBPP
      reduces myocardial oxygen consumption during exercise. These results suggest that
      heart rate responses to LBPP during exercise vary with increasing age. 

PMID- 23869891
TI  - Endothelial dysfunction in femoral artery of the hypertensive rats is nitric
      oxide independent.
AB  - This study examined nitric oxide (NO) production, oxidative load and endothelium
      dependent relaxation (NO-dependent and NO-independent) in adult male borderline
      hypertensive (BHR) and spontaneously hypertensive (SHR) rats as compared to
      normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressure (BP) was determined
      by tail-cuff. NO production was determined by conversion of [(3)H]-L-arginine.
      Conjugated dienes (CD) and concentrations of thiobarbituric acid-reactive
      substances (TBARS) were measured for assessment of oxidative load. Vascular
      function was investigated in rings of the femoral artery (FA) using a wire
      myograph. BP of WKY, BHR and SHR was 106+/-2, 143+/-3 and 191+/-3 mm Hg,
      respectively (p<0.01 for each). Significant left ventricle (LV) hypertrophy and
      elevated levels of CD and TBARS in the LV were present in BHR and SHR as compared
      to WKY. NO production was elevated significantly in the aorta of BHR and SHR vs.
      WKY as well as in the LV of SHR vs. WKY. Acetylcholine (ACh)-induced relaxation
      of the FA was reduced significantly in both BHR and SHR vs. WKY. The NO-dependent
      component of ACh-induced relaxation had increasing tendency in hypertensive
      groups and it correlated positively with BP. The NO-independent component of
      vasorelaxation was reduced significantly in BHR and SHR vs. WKY and it correlated
      negatively with BP. In conclusion, the results showed that endothelial
      dysfunction in the experimental model of borderline hypertensive and hypertensive
      rats is NO-independent. The results suggest that borderline hypertension
      represents a risk of other cardiovascular disorders which is qualitatively
      similar to that of fully developed hypertension. 

PMID- 23869892
TI  - VO2 kinetics in supra-anaerobic threshold constant tests allow the visualization
      and quantification of the O2 saving after cytochrome c oxidase inhibition by
      aerobic training or nitrate administration.
AB  - We tested whether the known cytochrome c oxidase (COX) inhibition by nitric oxide
      (NO) could be quantified by VO(2) kinetics during constant load supra-Anaerobic
      Threshold (AT) exercises in healthy trained or untrained subjects following
      aerobic training or nitrate administration. In cycle ergometer constant load
      exercises supra-AT, identified in previous incremental tests, VO(2) kinetics
      describe a double exponential curve, one rapid and one appreciably slower,
      allowing the area between them to be calculate in O(2) l. After training, with
      increased NO availability, this area decreases in inverse ratio to treatment
      efficacy. In fact, in 11 healthy subjects after aerobic training for 6-7 weeks,
      area was decreased on average by 51 %. In 11 untrained subjects, following the
      assumption of an NO donor, 20 mg isosorbide 5 mononitrate, area was decreased on
      average by 53 %. In conclusion, supra-AT VO(2) kinetics in constant load
      exercises permit the quantification of the inhibitory effect NO-dependent on COX
      after either physical training or nitrate assumption. 

PMID- 23869893
TI  - In vivo study of radioprotective effect of NO-synthase inhibitors and acetyl-L
      carnitine.
AB  - This study investigated the protective effect of two nitric oxide synthase
      inhibitors N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg i.p.) and
      aminoguanidine (AG, 400 mg/kg i.p.), and an antioxidant acetyl-L-carnitine (ALC,
      250 mg/kg i.p., once daily for five days) against radiation-induced damage in
      Wistar rats. Blood samples were collected 6 h after whole-body irradiation with 8
      Gy. Plasma concentrations of nitrite+nitrate (NO(x)) and malondialdehyde (MDA)
      were measured by high-performance liquid chromatography. A single injection of L
      NAME one hour before exposure effectively prevented the radiation-induced
      elevation of plasma NO(x) and it reduced 2.6-fold the risk for death during the
      subsequent 30-day period. Pretreatment with ALC prevented the radiation-induced
      increase in plasma MDA and it had similar effect on mortality as L-NAME did.
      Presumably due to its short half-life, the partially iNOS-selective inhibitor and
      antioxidant AG given in a single dose before exposure did not attenuate MDA and
      NO(x) and it failed to significantly improve the 30-day survival. In conclusion,
      pretreatment with both the nonspecific NOS inhibitor L-NAME and the antioxidant
      ALC markedly reduce mortality to radiation sickness in rats. The radioprotective
      effect may be directly related to effective attenuation of the radiation-induced
      elevation of NO production by L-NAME and of oxidative stress by ALC. 

PMID- 23869894
TI  - Effect of the MTHFR 677C/T polymorphism on homocysteinemia in response to
      creatine supplementation: a case study.
AB  - Creatine (Cr) is recommended as a dietary supplement especially for athletes but
      its therapeutic potential is also discussed. It is assumed that human body uses
      Cr for the formation of phosphocreatine, which is necessary for muscular work as
      a source of energy. Production of Cr in a body is closely connected to methionine
      cycle where guanidinoacetate (GAA) is in a final step methylated from S
      adenosylmethionine (SAM). Increased availability of SAM for phosphatidylcholine
      (PC) and sarcosine synthesis can potentially stimulate endogenous production of
      betaine a thus methylation of homocysteine (HCy) to form methionine. Our subject
      who was methylenetetrahydrofolate reductase (MTHFR) 677TT homozygote lowered
      plasma HCy from 33.3 micromol/l to 17.1 micromol/l following one-month Cr
      supplementation (5 g/day) opposite to 677CC and CT genotypes whose HCy levels
      tended to increase (but still in normal ranges). We suppose that Cr
      supplementation stimulates pathways leading to production of sarcosine which can
      serve to regenerate tetrahydrofolate (THF) to form 5,10-methylene-THF. This could
      potentially increase MTHFR enzyme activity which may later result in increased
      HCy methylation. Cr supplementation significantly effects metabolism of one
      carbon unit and potentially lower body's demands for methyl groups. This could be
      beneficial as in the case of reduced enzyme activity such as MTHFR 677C/T
      polymorphism. 

PMID- 23869895
TI  - Diagnostic significance of a mild decrease of baroreflex sensitivity with respect
      to heart rate in type 1 diabetes mellitus.
AB  - Decreased baroreflex sensitivity is an early sign of autonomic dysfunction in
      patients with type-1 diabetes mellitus. We evaluated the repeatability of a mild
      baroreflex sensitivity decrease in diabetics with respect to their heart rate.
      Finger blood pressure was continuously recorded in 14 young diabetics without
      clinical signs of autonomic dysfunction and in 14 age-matched controls for 42
      min. The recordings were divided into 3-min segments, and the mean inter-beat
      interval (IBI), baroreflex sensitivity in ms/mm Hg (BRS) and mHz/mm Hg (BRSf)
      were determined in each segment. These values fluctuated in each subject within
      42 min and therefore coefficients of repeatability were calculated for all
      subjects. Diabetics compared with controls had a decreased mean BRS (p=0.05), a
      tendency to a shortened IBI (p=0.08), and a decreased BRSf (p=0.17). IBI
      correlated with BRS in diabetics (p=0.03); this correlation was at p=0.12 in the
      controls. BRSf was IBI independent (controls: p=0.81, diabetics: p=0.29). We
      conclude that BRS is partially dependent on mean IBI. Thus, BRS reflects not only
      an impairment of the quick baroreflex responses of IBI to blood pressure changes,
      but also a change of the tonic sympathetic and parasympathetic heart rate
      control. This is of significance during mild changes of BRS. Therefore, an
      examination of the BRSf index is highly recommended, because this examination
      improves the diagnostic value of the measurement, particularly in cases of early
      signs of autonomic dysfunction. 

PMID- 23869896
TI  - Brain natriuretic peptide and NT-proBNP levels reflect pulmonary artery systolic
      pressure in trekkers at high altitude.
AB  - Our objective was to evaluate the utility of the natriuretic peptides BNP (brain
      natriuretic peptide) and NT-proBNP as markers of pulmonary artery systolic
      pressure (PASP) in trekkers ascending to high altitude (HA). 20 participants had
      BNP and NT-proBNP assayed and simultaneous echocardiographic assessment of PASP
      performed during a trek to 5150 m. PASP increased significantly (p=0.006) with
      ascent from 24+/-4 to 39+/-11 mm Hg at 5150 m. At 5150 m those with a PASP>/=40
      mm Hg (n=8) (versus those with PASP<40 mm Hg) had higher post-exercise BNP
      (pg/ml): 54.5+/-36 vs. 13.4+/-17 (p=0.012). Their resting BNP at 5150 m was also
      higher: 57.3+/-43.4 vs. 12.6+/-13 (p=0.017). In those with a pathological (>/=400
      pg/ml) rise in NT-proBNP at 5150 m (n=4) PASP was significantly higher: 45.9+/
      7.5 vs. 32.2+/-6.2 mm Hg (p=0.015). BNP and NT-proBNP may reflect elevated PASP,
      a central feature of high altitude pulmonary oedema, at HA. 

PMID- 23869897
TI  - Hypercapnia attenuates the hypoxia-induced blunting of the reactivity in
      chronically hypoxic rats.
AB  - Chronic hypoxia causes oxidative injury of pulmonary vessels and attenuates their
      reactivity to different stimuli. When combined with hypercapnia, biochemical
      markers of this injury are reduced but the effect of concomitant hypoxia and
      hypercapnia on vascular reactivity is not fully understood. This study was
      therefore designed to test whether hypercapnia can prevent also the hypoxia
      induced loss of reactivity of pulmonary vessels. The reactivity of vessels from
      rats exposed either to hypoxia or hypoxia combined with hypercapnia was tested
      using a small vessel myograph (M 500A, Linton, Norfolk, GB). The second and third
      intrapulmonary branches of pulmonary arteries were isolated under a dissecting
      microscope from lungs of 8 control rats (group N), 6 rats exposed to hypoxia for
      5 days (isobaric, 10 % O(2), group H) and 7 rats exposed to hypoxia combined with
      hypercapnia for 5 days (10 % O(2), 5 % CO(2), group H+CO(2)). The transmural
      pressure was set by automatic normalization to 30 mm Hg. The vessel size did not
      vary among the groups. After stabilization we challenged the vessels twice with
      KCl (80 mM) and once with PGF(2alpha) (0.1 mM). There were no significant
      differences in KCl induced contractions among the groups. The responses to
      PGF(2alpha) were expressed as a ratio to the maximal tension obtained by the
      exposure to 80 mM KCl. Contractions induced by PGF(2alpha) were markedly reduced
      in group H (0.07+/-0.02) and in group H+CO(2) (0.26+/-0.03) in comparison with
      group N (0.83+/-0.07). The vessels of group H responded to PGF(2alpha) less than
      those of group H+CO(2). However we observed the attenuated reactivity also in
      group H+CO(2) in comparison with N. Hypercapnia therefore partially blunted the
      hypoxia-induced loss of reactivity in pulmonary arteries. This finding supports
      the hypothesis that hypercapnia significantly alters the nature of lung injury
      induced by chronic hypoxia. 

PMID- 23869898
TI  - Multifunctional PLGA-based nanoparticles encapsulating simultaneously hydrophilic
      antigen and hydrophobic immunomodulator for mucosal immunization.
AB  - We describe here the development of nanoparticles made from poly(lactic-co
      glycolic acid) (PLGA) able to deliver an encapsulated antigen with a Toll-Like
      Receptor-7 (TLR-7) agonist as immunostimulatory signal and coated with a muco
      adhesive chitosan-derivate layer. The potential to stimulate an immune response
      of these vaccine formulations in the absence or presence of the TLR-7 agonist at
      the systemic and mucosal level were evaluated in mice following subcutaneous or
      nasal administrations. Intranasally immunized mice developed a high systemic
      immune response equivalent to mice injected subcutaneously. However, mucosal
      immune responses were only induced at local and distal sites in mucosally
      immunized animals. The adjuvant effect of imiquimod on the polarization of the
      immune response was only detected at local sites, which tends to increase safety
      of this vaccine delivery system. 

PMID- 23869899
TI  - Caregiver outcomes of partners in dementia care: effect of a care coordination
      program for veterans with dementia and their family members and friends.
AB  - The objective is to test the effectiveness of Partners in Dementia Care (PDC), a
      care-coordination program that integrates and improves access to medical and
      nonmedical services, while strengthening the informal care network and providing
      information, coaching, and emotional support. PDC was delivered via a partnership
      between Veterans Affairs (VA) Medical Centers (VAMCs) and Alzheimer's Association
      chapters, for caregivers of veterans with dementia living in the community and
      receiving primary care from the VA. The initial sample was 486 caregivers of 508
      veterans with diagnosed dementia. Outcomes were evaluated for 394 and 324
      caregivers who completed 6- and 12- month follow-up, respectively. PDC had a
      standardized protocol that included assessment and reassessment, action planning,
      and ongoing monitoring. It was delivered by telephone and e-mail for cost
      efficiency and the ability to handle caseloads of 100 to 125. Care coordinators
      from VAMCs and Alzheimer's Association chapters worked as a team using a shared
      computerized record. A variety of caregiver outcomes was measured after 6 and 12
      months. Intervention group caregivers had significant improvements in outcomes
      representing unmet needs, three types of caregiver strains, depression, and two
      support resources. Most improvements were evident after 6 months, with more
      limited improvements from Months 6 to 12. Some outcomes improved for all
      caregivers, whereas some improved for caregivers experiencing more initial
      difficulties or caring for veterans with more-severe impairments. PDC is a
      promising model that improves linkages between healthcare services and community
      services, which is a goal of several new national initiatives such as the
      National Plan to Address Alzheimer's Disease and a proposed amendment to the
      Older Americans Act.

PMID- 23869900
TI  - The biology of leptin and its implications in breast cancer: a general view.
AB  - Obesity is a world health problem that increases the risk for developing type 2
      diabetes, cardiovascular disease, fatty liver, and some types of cancer. In
      postmenopausal women, it represents an important risk factor for the development
      of breast cancer (BC). Leptin is an adipokine that is secreted by fatty tissue,
      and high leptin levels are observed both in mouse models of obesity and in obese
      subjects. High levels of leptin promote the proliferation and progression of
      various types of cancer, including BC. This review provides a general overview of
      the biology of leptin, important laboratory studies, and animal and clinical
      models that have provided evidence for an active role of leptin in the
      proliferation, progression, and survival of mammary tumors. Finally, this review
      addresses the most recent studies on the use of leptin receptor antagonists as a
      novel therapeutic treatment for BC. 

PMID- 23869901
TI  - Hypalgesia effect of IL-24, a quite new mechanism for IL-24 application in cancer
      treatment.
AB  - Tumor suppressor melanoma differentiation-associated gene-7/interleukin-24 (mda
      7/IL-24) has been extensively regarded as an anti-oncogene; however, that whether
      IL-24, as a member of IL-10 family, is involved in cancer pain was seldom
      reported before. In this study, we found that IL-24 mediated by adenovirus could
      significantly increase the plantar mechanical pain threshold in both operation
      side and contralateral side of the animal models, which were established by
      injecting 5*103 Walker 256 rat breast cancer ascitic tumor cells into rats' tibia
      bone medullary canals; IL-24 could also suppress in vitro Walker 256 cells growth
      by inducing cell apoptosis. Pathologically, IL-24 could protect bone trabecula
      and substantia corticalis ossium from being completely destructed. Enzyme-linked
      immunosorbent assay (ELISA) showed that IL-24 treatment could increase the beta
      endorphin levels and decrease the IL-6 concentration in plasma of animals. Our
      study indicated that IL-24 has a potential treatment effect on cancers not only
      by inhibiting tumor proliferation, but also by the promotion of beta-endorphin
      synthesis, inhibition of IL-6 secretion to relieve cancer pain. 

PMID- 23869902
TI  - Understanding the role of vanadium in enhancing the low-temperature hydrogenation
      kinetics of an Mg thin film.
AB  - Mg100-xVx (x = 0 to 15) thin films capped with Pd were prepared by electron beam
      codeposition and studied for their hydrogenation/dehydrogenation kinetics and
      cycling properties at 140  degrees C under hydrogenation pressures of 0.1 MPa. It
      has been found that the Mg100-xVx thin films show significantly higher reversible
      hydrogen-storage capacity and faster kinetics in comparison with a pure Mg thin
      film; for instance, the maximum hydrogen absorption (3.7% mass fraction hydrogen)
      can be obtained in the fifth cycle for Mg90V10 in less than 5 min. The addition
      of V clearly plays a favorable role in improving the reversible hydrogen-storage
      capacity of an Mg film; however, with increasing hydrogenation/dehydrogenation
      cycles the hydrogen-storage capacity gradually deteriorates. To explore the
      origin of the effect of V on the improved hydrogenation of an Mg thin film, in
      this work we focused on studying the structural variations of the Mg90V10 thin
      film before and after hydrogenation at different stages of cycling; the films
      were investigated by X-ray diffraction as well as scanning and transmission
      electron microscopy. We concluded that (1) early in the absorption/desorption
      cycling the as-deposited structure of percolating layers of nanocrystalline V
      throughout a Mg matrix is preserved; (2) the percolating V layers envelope fine
      Mg grains and act as (a) dispersers that isolate small Mg grains, (b) fast
      diffusers of hydrogen, and (c) hydrogen catalysts at the Mg/V interface to form
      MgH2; and (3) with progressive cycling, the continuous layers of V aggregate to
      spherical nanoparticles, which interrupts the continuity of fast hydrogen
      diffusion through V. 

PMID- 23869903
TI  - Assessment of psoriatic plaque in vivo with correlation mapping optical coherence
      tomography.
AB  - BACKGROUND/PURPOSE: Vascular abnormalities play an acute role in the pathogenesis
      of psoriasis. In order to characterize vascular involvement in psoriasis and its
      regular clinical assessment in vivo, non-invasive high speed imaging with high
      resolution and high sensitivity is needed. METHODS: The correlation mapping
      optical coherence tomography (cmOCT) technique was used for in vivo
      microcirculation imaging of human forearm under normal and psoriatic conditions.
      The cmOCT technique developed by our group uses dense scanning OCT image
      acquisition and post-processing software based on correlation statistics. The
      frequency domain OCT system was used for imaging which acquires a 3D volume of
      1024 * 1024 A-scans, each of 512 pixels deep in approximately 70 s. The cmOCT
      technique processes the resulting OCT volume within 116 s using a 7 * 7 kernel.
      RESULTS: 3D structural and functional (microcirculation) maps of the healthy
      tissue and the psoriatic plaque were obtained using the cmOCT technique. The
      presented results indicate that cmOCT allows not only the identification of the
      microvessels, but also produces more detailed microvascular networks showing how
      the blood vessels relate to each other in healthy tissue and within the plaque.
      The microcirculation pattern within the plaque is totally different from the
      healthy tissue. The distinct changes are also observed in vessel density,
      tortuosity, and orientation. CONCLUSION: The cmOCT provides high sensitivity and
      imaging speed for in vivo microcirculation imaging within the human skin under
      normal and diseased conditions.

PMID- 23869904
TI  - Dietary intake of dioxins, furans and dioxin-like PCBs in Austria.
AB  - Human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)
      and dioxin-like PCBs (dl-PCBs) should be assessed regularly. In order to evaluate
      the contamination levels in various food products on the Austrian market and to
      assess the dietary exposure of the Austrian population for the first time, a
      national monitoring programme was conducted from 2005 to 2011. The 235 food
      products comprised meat, poultry, game and offal, fish and fish products, milk
      and dairy products, eggs, animal fats and vegetable oils. To estimate the dietary
      intakes of PCDD/Fs and dl-PCBs, mean concentrations in food were combined with
      the respective food consumption data from the Austrian food consumption survey.
      Estimated dietary intakes were expressed as toxic equivalents (WHO-TEQs 1998).
      The mean intakes for PCDD/Fs and dl-PCBs were estimated as 0.77, 0.75 and 0.61 pg
      WHO-TEQ kg(-1) bw day(-1) for children, women and men, respectively. The main
      contributors to total intake were milk and dairy products followed by fish and
      fish products for children and women, and meat, poultry, game and offal for men
      (65% and 15% for children, 67% and 14% for women, and 63% and 19% for men,
      respectively). Comparison of the estimated dietary intakes with the toxicological
      reference values shows that both children and adults are well below those values.

PMID- 23869905
TI  - Reporting adverse events in randomized controlled trials in periodontology: a
      systematic review.
AB  - BACKGROUND/AIMS: Reporting of adverse events is of paramount importance in
      randomized controlled trials (RCTs) to guide the implementation of new
      therapeutic approaches in clinical practice. The aim of this study was to assess
      the quality of adverse events reporting in RCTs published in the periodontal
      literature. MATERIALS AND METHODS: Two authors (CMF and NNG) searched the PubMed
      and LILACS electronic databases independently and in duplicate to identify RCTs
      published in periodontology from 2002 to 2003 and from 2011 to 2012. Reporting
      quality in RCTs was assessed with reference to the 2004 CONSORT Extension for
      Harms checklist. Differences in adverse events reporting between industry- and
      non-industry-funded RCTs were also determined. Cohen's kappa statistic was used
      to determine the extent of inter-reviewer agreement. Fischer's exact test was
      used to assess differences in reporting between the two samples. RESULTS: The
      analysis included 246 publications. One hundred twenty-four of 990 (13%) items
      and 223 of 1460 (15%) items were adequately reported in publications from 2002 to
      2003 and from 2011 to 2012 respectively. Three checklist topics were
      significantly better reported in the 2011-2012 sample; two recommendations were
      better reported in non-industry-funded trials in publications from both periods.
      CONCLUSION: Improvement and standardization of adverse events reporting in
      periodontology are needed.

PMID- 23869906
TI  - The solubility and stability of amino acids in biocompatible ionic liquids.
AB  - In recent years, ionic liquids (ILs) represent a new class of biocompatible co
      solvents for biomolecules. In this work, we report the apparent transfer free
      energies (DeltaG'tr) for six amino acids (AA) from water to aqueous solutions of
      six ammonium based ILs (diethylammonium acetate (DEAA), diethylammonium sulfate
      (DEAS), triethyl ammonium acetate (TEAA), triethylammonium sulfate (TEAS),
      triethylammonium dihydrogen phosphate (TEAP), and trimethylammonium acetate
      (TMAA)) through solubility measurements, as a function of IL concentration at
      298.15 K under atmospheric pressure. Salting-out effect was found for AA in
      aqueous IL solutions with increasing IL concentrations. In addition, we observed
      positive values of DeltaG'tr for AA from water to ILs, indicating that the
      interactions between ILs and AA are unfavorable. From the obtained results, we
      found that the selected ammonium based ILs act as stabilizers for the structure
      of AA. 

PMID- 23869907
TI  - Impact of psychotropic drugs on suicide and suicidal behaviors.
AB  - OBJECTIVE: To examine the impact of psychotropic drugs on suicide and suicidal
      behaviors in bipolar disorders. METHODS: A Medline search of articles published
      from January 1960 to January 2013 was performed using relevant keywords to
      identify studies examining the relationship of psychotropic drugs to suicidal
      behaviors. The publications were further reviewed for relevant references and
      information. Additionally, the US Food and Drug Administration Center for Drug
      Evaluation Research website was searched. RESULTS: The available studies used
      differing methodologies, making interpretation of the findings difficult. Studies
      suggest that antidepressants may increase suicidal risk in bipolar disorder, this
      possibly being related to the induction of broadly defined mixed states. There is
      no evidence that antiepileptic drugs as a class increase suicidal risk in
      patients with bipolar disorder. Only lithium provides convincing data that it
      reduces the risk of suicide over the long term. There is little known regarding
      the effects of antipsychotics, as well as anti-anxiety and hypnotic drugs, on
      suicidal behavior. CONCLUSIONS: The available evidence for the impact of
      psychotropics on suicidal risk in patients with bipolar disorder is largely
      methodologically flawed and, except for a few instances, clinically not useful at
      this point. Adequately powered, prospective randomized controlled studies are
      needed to assess the impact of each class of psychotropic and each psychotropic
      as well as common combination therapies. Until such studies have been carried
      out, clinicians are urged to exercise caution in using these drugs and rely on
      the traditional means of carefully assessing and monitoring patients with bipolar
      disorder who are at high risk for suicide.

PMID- 23869909
TI  - Gestational diabetes predicts the risk of childhood overweight and abdominal
      circumference independent of maternal obesity.
AB  - AIM: Gestational diabetes mellitus is believed to be a risk factor for childhood
      overweight/obesity. We aimed to assess whether this association is either a
      reflection or independent of confounding by maternal BMI. METHODS: Data from 7355
      mother-child dyads of the German Perinatal Prevention of Obesity cohort with full
      anthropometric information on mothers and children, gestational diabetes and
      confounding factors were obtained at school entry health examination. We
      calculated crude and adjusted logistic regression models for the association of
      gestational diabetes and childhood overweight/obesity and abdominal adiposity
      defined by age- and sex-specific percentiles for BMI and waist circumference.
      RESULTS: Among all children (mean age 5.8 years), 8.1% were overweight, 2.6% were
      obese and 15.5% had abdominal adiposity. The prevalence of overweight (obesity)
      was 21% (8.2%) in children of mothers with gestational diabetes and 10.4% (2.4%)
      in children of healthy mothers. Analyses with adjustment for maternal BMI and
      other potential confounders yielded an odds ratio of 1.81 (95% CI 1.23-2.65) and
      2.80 (95% CI 1.58-4.99) for the impact of gestational diabetes on childhood
      overweight and obesity, respectively. Similar results were obtained for the risk
      of childhood abdominal adiposity (odds ratio 1.64, 95% CI 1.16-2.33) by maternal
      gestational diabetes. CONCLUSIONS: The postulated increased risk of overweight
      and abdominal adiposity in offspring of mothers with gestational diabetes cannot
      be explained by maternal BMI alone and may be stronger for childhood obesity than
      for overweight.

PMID- 23869908
TI  - Functional characterization of human CTC1 mutations reveals novel mechanisms
      responsible for the pathogenesis of the telomere disease Coats plus.
AB  - Coats plus is a rare recessive disorder characterized by intracranial
      calcifications, hematological abnormalities, and retinal vascular defects. This
      disease results from mutations in CTC1, a member of the CTC1-STN1-TEN1 (CST)
      complex critical for telomere replication. Telomeres are specialized DNA/protein
      structures essential for the maintenance of genome stability. Several patients
      with Coats plus display critically shortened telomeres, suggesting that telomere
      dysfunction plays an important role in disease pathogenesis. These patients
      inherit CTC1 mutations in a compound heterozygous manner, with one allele
      encoding a frameshift mutant and the other a missense mutant. How these mutations
      impact upon telomere function is unknown. We report here the first biochemical
      characterization of human CTC1 mutations. We found that all CTC1 frameshift
      mutations generated truncated or unstable protein products, none of which were
      able to form a complex with STN1-TEN1 on telomeres, resulting in progressive
      telomere shortening and formation of fused chromosomes. Missense mutations are
      able to form the CST complex at telomeres, but their expression levels are often
      repressed by the frameshift mutants. Our results also demonstrate for the first
      time that CTC1 mutations promote telomere dysfunction by decreasing the stability
      of STN1 to reduce its ability to interact with DNA Polalpha, thus highlighting a
      previously unknown mechanism to induce telomere dysfunction. 

PMID- 23869910
TI  - Determination of the ortho to para ratio of H2Cl+ and H2O+ from submillimeter
      observations.
AB  - The opening of the submillimeter sky with the Herschel Space Observatory has led
      to the detection of new interstellar molecular ions, H2O(+), H2Cl(+), and HCl(+),
      which are important intermediates in the synthesis of water vapor and hydrogen
      chloride. In this paper, we report new observations of H2O(+) and H2Cl(+)
      performed with both Herschel and ground-based telescopes, to determine the
      abundances of their ortho and para forms separately and derive the ortho-to-para
      ratio. At the achieved signal-to-noise ratio, the observations are consistent
      with an ortho-to-para ratios of 3 for both H2O(+) and H2Cl(+), in all velocity
      components detected along the lines-of-sight to the massive star-forming regions
      W31C and W49N. We discuss the mechanisms that contribute to establishing the
      observed ortho-to-para ratio and point to the need for a better understanding of
      chemical reactions, which are important for establishing the H2O(+) and H2Cl(+)
      ortho-to-para ratios. 

PMID- 23869911
TI  - Virulence loss and amastigote transformation failure determine host cell
      responses to Leishmania mexicana.
AB  - The effect of alterations in virulence and transformation by long-term in vitro
      culture of Leishmania mexicana promastigotes on infectivity and immune responses
      was investigated. Fresh parasite cultures harvested from Balb/c mice were
      passaged 20 times in vitro. Infectivity was decreased and was completely
      avirulent after 20 passages. The qPCR results showed a down-regulation of GP63,
      LPG2, CPC, CPB2, CPB2.8, CHT1, LACK and LDCEN3 genes after passage seven
      concomitant with a reduced and absence of infectivity by passages seven and 20,
      respectively. Parasites at passages one and 20 are referred to as virulent and
      avirulent, respectively. The growth of avirulent and virulent parasite was
      affected by conditioned media derived from macrophages or monocytes infected with
      parasites for 2 h. Giemsa staining showed the failure of avirulent but not
      virulent parasites to transform to the amastigote stage in infected host cells
      with both virulent and avirulent modulating the expression of CCL-22, Tgad51,
      Cox2, IL-1, IL-10, TGF-beta, TNF-alpha, Rab7, Rab9 and A2 genes; virulent but not
      avirulent L. mexicana significantly up-regulated Th2-associated cytokines, but
      down-regulated Rab7 and Rab9 gene expression. In conclusion, a model for L.
      mexicana is reported, which is of potential value in studying host-parasite
      interaction.

PMID- 23869912
TI  - Inter-annual variability of urolithiasis epidemic from semi-arid part of Deccan
      Volcanic Province, India: climatic and hydrogeochemical perspectives.
AB  - Semi-arid Karha basin from Deccan Volcanic Province, India was investigated for
      inter-annual variability of urolithiasis epidemic. The number of reported urolith
      patient, weather station data and groundwater quality results was used to assess
      impact of geoenvironment on urolithiasis. Data of 7081 urolith patient were
      processed for epidemiological study. Gender class, age group, year-wise cases and
      urolith type were studied in epidemiology. Rainfall, temperature, pan evaporation
      and sunshine hours were used to correlate urolithiasis. Further, average values
      of groundwater parameters were correlated with the number of urolith episodes. A
      total of 52 urolith samples were collected from hospitals and analysed using FTIR
      technique to identify dominant urolith type in study area. Result shows that male
      population is more prone, age group of 20-40 is more susceptible and calcium
      oxalate uroliths are dominant in study area. Year-wise distribution revealed that
      there is steady increase in urolithiasis with inflation in drought years. In
      climatic parameters, hot days are significantly correlated with urolithiasis. In
      groundwater quality, EC, Na and F are convincingly correlated with urolith
      patients, which concludes the strong relation between geo-environment and
      urolithiasis. 

PMID- 23869913
TI  - Application of the anthropogenic allee effect model to trophy hunting as a
      conservation tool.
AB  - Trophy hunting can provide economic incentives to conserve wild species, but it
      can also involve risk when rare species are hunted. The anthropogenic Allee
      effect (AAE) is a conceptual model that seeks to explain how rarity may spread
      the seeds of further endangerment. The AAE model has increasingly been invoked in
      the context of trophy hunting, increasing concerns that such hunting may
      undermine rather than enhance conservation efforts. We question the
      appropriateness of uncritically applying the AAE model to trophy hunting for 4
      reasons. First, the AAE assumes an open-access resource, which is a poor
      characterization of most trophy-hunting programs and obscures the potential for
      state, communal, or private-property use rights to generate positive incentives
      for conservation. Second, study results that show the price of hunting increases
      as the rarity of the animal increases are insufficient to indicate the presence
      of AAE. Third, AAE ignores the existence of biological and behavioral factors
      operating in most trophy-hunting contexts that tend to regulate the effect of
      hunting. We argue that site-specific data, rather than aggregated hunting
      statistics, are required to demonstrate that patterns of unsustainable
      exploitation can be well explained by an AAE model. Instead, we suggest that
      conservation managers seeking to investigate and identify constraints that limit
      the potential conservation role of trophy hunting, should focus on the critical
      governance characteristics that shape the potential conservation role of trophy
      hunting, such as corruption, insecure property rights, and inadequate sharing of
      benefits with local people.

PMID- 23869914
TI  - Kinetics and low temperature studies of electron transfers in films of small (<2
      nm) Au monolayer protected clusters.
AB  - This work examines the temperature dependence of electron transfer (ET) kinetics
      in solid-state films of mixed-valent states of monodisperse, small (<2 nm) Au
      monolayer protected clusters (MPCs). The mixed valent MPC films, coated on
      interdigitated array electrodes, are Au25(SR)18(0/1-), Au25(SR)18(1+/0), and
      Au144(SR)60(1+/0), where SR = hexanethiolate for Au144 and phenylethanethiolate
      for Au25. Near room temperature and for ca. 1:1 mol:mol mixed valencies, the
      bimolecular ET rate constants (assuming a cubic lattice model) are ~2 * 10(6) M(
      1) s(-1) for Au25(SR)18(0/1-), ~3 * 10(5) M(-1) s(-1) for Au25(SR)18(1+/0), and
      ~1 * 10(8) M(-1) s(-1) for Au144(SR)60(1+/0). Their activation energy ET barriers
      are 0.38, 0.34, and 0.17 eV, respectively. At lowered temperatures (down to ca.
      77 K), the thermally activated (Arrhenius) ET process dissipates revealing a
      tunneling mechanism in which the ET rates are independent of temperature but,
      among the different MPCs, fall in the same order of ET rate: Au144(+1/0) >
      Au25(0/1-) > Au25(1+/0).

PMID- 23869916
TI  - ABC3 and LBC - adequate or not?

PMID- 23869918
TI  - Long-term outcomes in children with swallowing dysfunction.
AB  - PURPOSE: To evaluate swallowing function using a videofluoroscopic swallow study
      (VFSS), and to identify factors related to long-term swallowing function in
      children with swallowing dysfunction. METHODS: Ninety children, aged 1-120 months
      (mean 27.5 months) were randomly selected from among children referred for the
      evaluation of swallowing dysfunction. We retrospectively reviewed the charts, and
      long-term outcomes were tracked up to 5 years. RESULTS: Baseline American Speech
      Language-Hearing Association National Outcome Measurement System (ASHA NOMS)
      scale was 3.4 +/- 2.5. Supraglottic penetration and subglottic aspiration
      comfirmed by VFSS were detected in 30 children. After follow-up, oral feeding was
      possible in 74 patients, and the ASHA NOMS swallowing scale improved
      significantly, from 3.4 +/- 2.5 to 5.8 +/- 2.0. Baseline VFSS severity, serum
      albumin concentration, baseline weight percentile and neurologic conditions were
      significantly correlated with long-term swallowing function. CONCLUSIONS: The
      long-term outcomes in children with swallowing dysfunction were favorable, and
      baseline videofluoroscopic severity was significantly correlated with long-term
      swallowing function.

PMID- 23869919
TI  - Comparative outcomes of elderly and non-elderly patients receiving first-line
      palliative chemotherapy for advanced biliary tract cancer.
AB  - BACKGROUND AND AIM: Few studies have reported the efficacy and safety of
      palliative chemotherapy in elderly patients with advanced biliary tract cancer.
      We aimed to investigate the clinical outcomes of palliative chemotherapy for
      advanced biliary tract cancer in elderly patients. METHODS: We retrospectively
      evaluated 403 consecutive patients who received palliative chemotherapy between
      April 2006 and March 2009 for pathologically confirmed unresectable or recurrent
      biliary tract cancer. Clinical outcomes of the elderly group (>= 75 years old; n
      = 94) were compared with those of the non-elderly group (< 75 years old; n =
      309). RESULTS: Except for the extent of disease, patient baseline characteristics
      were well balanced between both groups. The median overall survival was 10.4
      months in the elderly group and 11.5 months in the non-elderly group (hazard
      ratio, 1.14; 95% confidence interval, 0.89-1.45; P = 0.31). Although the
      frequency of adverse events between both groups was similar, interstitial
      pneumonitis was significantly more frequent in the elderly group than in the non
      elderly group (4.3% vs 0%, P < 0.01). CONCLUSIONS: In advanced biliary tract
      cancer, overall survival of elderly patients receiving palliative chemotherapy is
      comparable with that of non-elderly patients. To our knowledge, this is one of
      the largest studies that have reported the clinical outcomes of elderly patients
      following palliative chemotherapy.

PMID- 23869920
TI  - A new heterotrophic dinoflagellate from the North-eastern Pacific,
      Protoperidinium fukuyoi: cyst-theca relationship, phylogeny, distribution and
      ecology.
AB  - The cyst-theca relationship of Protoperidinium fukuyoi n. sp. (Dinoflagellata,
      Protoperidiniaceae) is established by incubating resting cysts from estuarine
      sediments off southern Vancouver Island, British Columbia, Canada, and San Pedro
      Harbor, California, USA. The cysts have a brown-coloured wall, and are
      characterized by a saphopylic archeopyle comprising three apical plates, the
      apical pore plate and canal plate; and acuminate processes typically arranged in
      linear clusters. We elucidate the phylogenetic relationship of P. fukuyoi through
      large and small subunit (LSU and SSU) rDNA sequences, and also report the SSU of
      the cyst-defined species Islandinium minutum (Harland & Reid) Head et al. 2001.
      Molecular phylogenetic analysis by SSU rDNA shows that both species are closely
      related to Protoperidinium americanum (Gran & Braarud 1935) Balech 1974. Large
      subunit rDNA phylogeny also supports a close relationship between P. fukuyoi and
      P. americanum. Three subgroups in total are further characterized within the
      Monovela group. The cyst of P. fukuyoi shows a wide geographical range along the
      coastal tropical to temperate areas of the North-east Pacific, its distribution
      reflecting optimal summer sea-surface temperatures of ~14-18  degrees C and
      salinities of 22-34 psu. 

PMID- 23869922
TI  - The chlamydial OTU domain-containing protein ChlaOTU is an early type III
      secretion effector targeting ubiquitin and NDP52.
AB  - Chlamydia are obligate intracellular pathogens. Upon contact with the host, they
      use type III secretion to deliver proteins into the cell, thereby triggering
      actin-dependent entry and establishing the infection. We observed that Chlamydia
      caviae elicited a local and transient accumulation of ubiquitinated proteins at
      the entry sites, which disappeared within 20 min. We investigated the mechanism
      for the rapid clearance of ubiquitin. We showed that the OTU-like domain
      containing protein CCA00261, predicted to have deubiquitinase activity, was
      detected in infectious particles and was a type III secretion effector. This
      protein is present in several Chlamydia strains, including the human pathogen
      Chlamydia pneumoniae, and we further designate it as ChlaOTU. We demonstrated
      that ChlaOTU bound ubiquitin and NDP52, and we mapped these interactions to
      distinct domains. NDP52 was recruited to Chlamydia entry sites and was
      dispensable for infection and for bacterial growth. ChlaOTU functioned as a
      deubiquitinase in vitro. Heterologousexpression of ChlaOTU reduced ubiquitin
      accumulation at the entry sites, while a catalytic mutant of the deubiquitinase
      activity had the opposite effect. Altogether, we have identified a novel secreted
      protein of chlamydiae. ChlaOTU targets both ubiquitin and NDP52 and likely
      participates in the clearance of ubiquitin at the invasion sites.

PMID- 23869923
TI  - Malignancies of the eyelid: a review of primary and metastatic cancers.
AB  - The eyelid can be the site of various malignant tumors, including epithelial,
      mesenchymal, lymphoproliferative, and endocrine neoplasms, all of which can
      present in unusual ways or mimic benign processes, often requiring biopsy for a
      definitive diagnosis. This review article presents a broad overview of some of
      the malignancies that have been reported to occur in eyelids, addressing clinical
      presentation and natural history, histologic and immunostaining characteristics,
      and genetic associations where relevant. The unique combination of functional
      importance, to protect and lubricate the eye, and cosmetic importance make
      management of eyelid lesions difficult. We describe a few of the diagnostic and
      treatment options that can be considered. 

PMID- 23869924
TI  - The dermatological consequences of obesity.
AB  - Obesity is emerging as a global epidemic with at least 300 million people thought
      to be obese worldwide. This has implications for health professionals including
      dermatologists. Recent interest has focused on the role of obesity in psoriasis,
      but obesity is implicated in many dermatoses. Perhaps most worrying is emerging
      data which suggest that obesity may constitute a risk factor for the development
      of skin cancer. Its rising incidence ensures that obesity-related skin disease
      will represent an increasing proportion of dermatologists' work load. In this
      article, we review dermatoses associated with obesity and review the epidemiology
      and treatment for obesity. 

PMID- 23869925
TI  - Enlarging hyperpigmented nodule on the right calf. Pencil-core granuloma.

PMID- 23869926
TI  - Asymptomatic linear pigmentation of the skin. Linear lichen planus pigmentus
      (LPP).

PMID- 23869927
TI  - Unusual milia amyloidosis as initial signs of multiple myeloma-associated
      systemic amyloidosis.

PMID- 23869928
TI  - Surgical treatment of basal cell carcinoma of the nail unit.

PMID- 23869929
TI  - Antiphospholipid antibody syndrome presenting with purpura fulminans.

PMID- 23869930
TI  - Tripe palms revealing renal cell carcinoma.

PMID- 23869931
TI  - Gemcitabine therapy-associated cutaneous vasculitis with a polyarteritis nodosa
      like pattern.

PMID- 23869932
TI  - Secondary amyloid deposition in a melanocytic nevus.

PMID- 23869934
TI  - Effects of response-related music stimulation versus general music stimulation on
      positive participation of patients with Alzheimer's disease.
AB  - OBJECTIVE: Assessing the effects of response-related music stimulation versus
      general (response-unrelated) music stimulation on positive participation of 11
      new patients with Alzheimer's disease. METHOD: The patients were functioning in
      the severe and low-moderate ranges of the disease. Positive participation
      included behaviors such as, singing or rhythmic movements and smiles. Both music
      conditions relied on the display of music/song videos on a computer screen. In
      the response-related (active) condition, the patients used a simple hand response
      and a microswitch to determine music stimulation inputs. In the general
      (unrelated/passive) condition, music stimulation was automatically presented
      throughout the sessions. RESULTS: Data showed that six of the 11 patients had
      higher levels of positive participation in the response-related stimulation
      condition. The remaining five patients did not have differences between the two
      conditions. CONCLUSION: Based on this evidence and previous findings, one might
      consider the use of the active condition beneficial for daily programs.

PMID- 23869935
TI  - Pumpkin (Cucurbita maxima) seed proteins: sequential extraction processing and
      fraction characterization.
AB  - Seed proteins extracted from Tunisian pumpkin seeds ( Cucurbita maxima ) were
      investigated for their solubility properties and sequentially extracted according
      to the Osborne procedure. The solubility of pumpkin proteins from seed flour was
      greatly influenced by pH changes and ionic strength, with higher values in the
      alkaline pH regions. It also depends on the seed defatting solvent. Protein
      solubility was decreased by using chloroform/methanol (CM) for lipid extraction
      instead of pentane (P). On the basis of differential solubility fractionation and
      depending on the defatting method, the alkali extract (AE) was the major fraction
      (42.1 (P), 22.3% (CM)) compared to the salt extract (8.6 (P), 7.5% (CM)). In
      salt, alkali, and isopropanol extracts, all essential amino acids with the
      exceptions of threonine and lysine met the minimum requirements for preschool
      children (FAO/WHO/UNU). The denaturation temperatures were 96.6 and 93.4  degrees
      C for salt and alkali extracts, respectively. Pumpkin protein extracts with
      unique protein profiles and higher denaturation temperatures could impart novel
      characteristics when used as food ingredients.

PMID- 23869936
TI  - Systematic review: Effective characteristics of nursing homes and other
      residential long-term care settings for people with dementia.
AB  - OBJECTIVES: In response to the need for an evidence-based review of factors
      within long-term care settings that affect the quality of care, this review
      compared characteristics of nursing homes and other residential long-term care
      settings for people with dementia and their informal family caregivers with
      respect to health and psychosocial outcomes. DESIGN: Databases were searched for
      literature published between 1990 and March 2012 that met review criteria,
      including that at least 80% of the subject population had dementia. RESULTS:
      Fourteen articles meeting review criteria that were of at least fair quality were
      found: four prospective cohort studies, nine randomized controlled trials (RCTs),
      and one nonrandomized controlled trial. Overall, low or insufficient strength of
      evidence was found regarding the effect of most organizational characteristics,
      structures, and processes of care on health and psychosocial outcomes for people
      with dementia and no evidence for informal caregivers. Findings of moderate
      strength of evidence indicate that pleasant sensory stimulation reduces agitation
      for people with dementia. Also, although the strength of evidence is low,
      protocols for individualized care and to improve function result in better
      outcomes for these individuals. Finally, outcomes do not differ between nursing
      homes and residential care or assisted living settings for people with dementia
      except when medical care is indicated. CONCLUSION: Given the paucity of high
      quality studies in this area, additional research is needed to develop a
      sufficient evidence base to support consumer selection, practice, and policy
      regarding the best settings and characteristics of settings for residential long
      term care of people with dementia.

PMID- 23869937
TI  - Quantification, mechanism, and mitigation of active ingredient phase
      transformation in tablets.
AB  - Model tablet formulations containing thiamine hydrochloride [as a
      nonstoichiometric hydrate (NSH)] and dicalcium phosphate dihydrate (DCPD) were
      prepared. In intact tablets, the water released by dehydration of DCPD mediated
      the transition of NSH to thiamine hydrochloride hemihydrate (HH). The use of an X
      ray microdiffractometer with an area detector enabled us to rapidly and
      simultaneously monitor both the phase transformations. The spatial information,
      gained by monitoring the tablet from the surface to the core (depth profiling),
      revealed that both DCPD dehydration and HH formation progressed from the surface
      to the tablet core as a function of storage time. Film coating of the tablets
      with ethyl cellulose caused a decrease in both the reaction rates. There was a
      pronounced lag time, but once initiated, the transformations occurred
      simultaneously throughout the tablet. Thus the difference in the phase
      transformation behavior between the uncoated and the coated tablets could not
      have been discerned without the depth profiling. Incorporation of hydrophilic
      colloidal silica as a formulation component further slowed down the
      transformations. By acting as a water scavenger it maintained a very "dry"
      environment in the tablet matrix. Finally, by coating the NSH particles with
      hydrophobic colloidal silica, the formation of HH was further substantially
      decelerated. The microdiffractometric technique not only enabled direct analyses
      of tablets but also provided the critical spatial information. This helped in the
      selection of excipients with appropriate functionality to prevent the in situ
      phase transformations. 

PMID- 23869938
TI  - Inhibitory effect of high-dosage zinc oxide dietary supplementation on
      Campylobacter coli excretion in weaned piglets.
AB  - AIMS: This study investigated the impact of zinc oxide (ZnO) on Campylobacter
      coli by in vivo and in vitro assays. METHODS AND RESULTS: By in vitro growth
      inhibition assays, a high susceptibility of Camp. coli against ZnO could be
      observed. At concentrations >= 2.6 mmol l(-1) ZnO, a decline in cell numbers
      occurred. Quantitative real-time PCR assays demonstrated an up-regulation of the
      main oxidative stress gene (katA) in response to ZnO treatment. The expression
      level of katA was increased by fivefold after ZnO treatment. An experiment was
      carried out in pigs to elucidate the impact of ZnO as feed supplement on Camp.
      coli faecal excretion. Feeding a high-dosage ZnO concentration (3100 mg kg(-1) )
      to piglets significantly reduced the faecal excretion of Camp. coli by up to 1
      log CFU g(-1) as compared to animals receiving a low (40 mg kg(-1) ) or medium
      (100 mg kg(-1) ) ZnO diet. CONCLUSION: In vitro assays showed a high
      susceptibility of Camp. coli against ZnO. Adding high levels of ZnO to the diet
      of weaned piglets reduced Camp. coli excretion significantly. There is evidence
      for the induction of an oxidative stress response by ZnO supplementation in Camp.
      coli. SIGNIFICANCE AND IMPACT OF THE STUDY: Supplementation of a high-dosage ZnO
      diet to piglets can reduce the Camp. coli load, potentially leading to a lower
      contamination risk of meat during slaughter.

PMID- 23869939
TI  - Grafts enriched with subamnion-cord-lining mesenchymal stem cell angiogenic
      spheroids induce post-ischemic myocardial revascularization and preserve cardiac
      function in failing rat hearts.
AB  - A crucial question in post-ischemic cell therapy refers to the ideal method of
      cell delivery to the heart. We hypothesized that epicardial implantation of
      subamnion-cord-lining mesenchymal stem cells (CL-MSC) angiogenic spheroids
      embedded within fibrin grafts (SASG) facilitates donor cell survival and enhances
      cardiac function in failing rat hearts. Furthermore, we compared the efficacy of
      this approach applied through two delivery methods. Spheroids made of 1.5*10(4)
      human CL-MSC coated with 2*10(3) human umbilical vein endothelial cells were self
      assembled in hanging drops. SASG were constructed by embedding 150 spheroids in
      fibrin matrix. Except for untreated rats (MI, n=8), grafts were implanted 2 weeks
      after myocardial infarction upon confirmation of ensued heart failure through
      thoracotomy: SASG (n=8) and fibrin graft (FG, n=8); or video-assisted
      thoracoscopic surgery (VATS): SASG-VATS (n=8) and FG-VATS (n=7). In vivo CL-MSC
      survival was comparable between both SASG-treated groups throughout the study.
      SASG and SASG-VATS animals had decreased left ventricular end-diastolic pressure
      relative to untreated animals, and increased fractional shortening compared to MI
      and FG controls, 4 weeks after treatment. A 14.1% and 6.2% enhancement in
      ejection fraction from week 2 to 6 after injury was observed in SASG/SASG-VATS,
      paralleled by improvement in cardiac output. Treated hearts had smaller scar
      size, and more blood vessels than MI, while donor CL-MSC contributed to
      arteriogenesis within the graft and infarct areas. Taken together, our data
      suggest that SASG treatment has the potential to restore failing hearts by
      preserving cardiac function and inducing myocardial revascularization, while
      attenuating cardiac fibrosis. Furthermore, we introduce a method for minimally
      invasive in situ graft assembly. 

PMID- 23869940
TI  - Cost per responder analysis in patients with secondary hyperparathyroidism on
      dialysis treated with cinacalcet.
AB  - BACKGROUND: Growing financial pressure on US dialysis providers requires economic
      efficiency considerations. The objective of this study was to examine short-term
      economic efficiencies of a cinacalcet-based treatment approach for secondary
      hyperparathyroidism. METHODS: This study retrospectively assessed cost per
      biochemical response of the OPTIMA trial. OPTIMA was conducted in end-stage renal
      disease patients to compare biochemical control in patients receiving cinacalcet
      in addition to vitamin D sterols and phosphate binders vs patients receiving
      vitamin D sterol and phosphate binders alone. It explored three laboratory
      measurement response definitions from baseline to week 23: (1) decreases in
      parathyroid hormone (PTH) >=30%; (2) PTH <= 300 pg/ml; and (3) PTH <= 300 pg/mL,
      calcium <9.5 mg/dL and phosphorus <5.5 mg/dL. Medication use and costs were
      measured to calculate average costs and incremental cost per responder.
      Stratification by lower and higher baseline PTH assessed cost per response by
      disease severity. RESULTS: There were 38-77% more responders with cinacalcet vs
      control, depending on response definition. Mean (SD) per patient total medication
      costs were $5423 ($3698) for cinacalcet and $2633 ($2334) for control, leading to
      a mean difference of $2790 over 23 weeks. When response was defined as a decrease
      in PTH >= 30% from baseline, the average cost per responder was $11,266 for
      control vs $7027 for cinacalcet. The incremental cost per incremental responder
      ranged from $5186-$9168. Across all response measures, cost per responder was
      lower in patients with lower baseline PTH. CONCLUSIONS: Representing a more
      efficient allocation of economic resources over the short-term, cinacalcet-based
      treatment algorithm led to a lower cost per biochemical response, particularly in
      patients with lower disease severity, vs vitamin D sterols and phosphate binders
      alone. These findings should be interpreted alongside the study limitation of
      converting international trial-based medication utilization into US costs.

PMID- 23869941
TI  - Medical costs in the US of clinical events associated with oral anticoagulant
      (OAC) use compared to warfarin among non-valvular atrial fibrillation patients
      >=75 and <75 years of age, based on the ARISTOTLE, RE-LY, and ROCKET-AF trials.
AB  - OBJECTIVES: Based on clinical trials the oral anticoagulants (OACs) apixaban,
      dabigatran, and rivaroxaban are efficacious for reducing stroke risk for non
      valvular atrial fibrillation (NVAF) patients. Based on the clinical trials, this
      study evaluated the medical costs for clinical events among NVAF patients >=75
      and <75 years of age treated with individual OACs vs warfarin. METHODS: Rates for
      primary and secondary efficacy and safety outcomes (i.e., clinical events) among
      NVAF patients receiving warfarin or each of the OACs were determined for NVAF
      populations aged >=75 years and <75 years of age from the OAC vs warfarin trials.
      One-year incremental costs among patients with clinical events were obtained from
      published literature and inflation adjusted to 2010 costs. Medical costs,
      excluding medication costs, for clinical events associated with each OAC and
      warfarin were then estimated and compared. RESULTS: Among NVAF patients aged
      >=75, compared to warfarin, use of either apixaban or rivaroxaban was associated
      with a reduction in medical costs per patient year (apixaban = -$825, rivaroxaban
      =-$23), while dabigatran use was associated with increased medical costs of $180
      per patient year. Among NVAF patients <75 years of age medical costs per patient
      year were estimated to be reduced -$254, -$367, and -$88, for apixaban,
      dabigatran, and rivaroxaban, respectively, in comparison to warfarin.
      LIMITATIONS: This economic analysis was based on clinical trial data and,
      therefore, the direct application of the results to routine clinical practice
      will require further assessment. CONCLUSIONS: Difference in medical costs between
      OAC and warfarin treated NVAF patients vary by age group and individual OACs.
      Although reductions in medical costs for NVAF patients aged >=75 and <75 were
      observed for those using either apixaban or rivaroxaban vs warfarin, the
      reductions were greater per patient year for both the older and younger NVAF
      populations using apixaban.

PMID- 23869943
TI  - One-pot construction of functional mesoporous silica nanoparticles for the tumor
      acidity-activated synergistic chemotherapy of glioblastoma.
AB  - Mesoporous silica nanoparticles (MSNs) have proved to be an effective carrier for
      controlled drug release and can be functionalized easily for use as stimuli
      responsive vehicles. Here, a novel intelligent drug-delivery system (DDS),
      camptothecin (CPT)-loaded and doxorubicin (DOX)-conjugated MSN (CPT@MSN-hyd-DOX),
      is reported via a facile one-pot preparation for use in synergistic chemotherapy
      of glioblastoma. DOX was conjugated to MSNs via acid-labile hydrazone bonds, and
      CPT was loaded in the pores of the MSNs. At pH 6.5 (analogous to the pH in tumor
      tissues), a fast DOX release was observed that was attributed to the hydrolysis
      of the hydrazone bonds. In addition, a further burst release of DOX was found at
      pH 5.0 (analogous to the pH in lyso/endosomes of tumor cells), leading to a
      strong synergistic effect. In all, CPT and DOX could be delivered simultaneously
      into tumor cells, and this intelligent DDS has great potential for tumor-trigged
      drug release for use in the synergistic chemotherapy of tumors. 

PMID- 23869944
TI  - Alexithymia partly predicts pain, poor health and social difficulties in patients
      with temporomandibular disorders.
AB  - Temporomandibular disorders (TMD) are functional diseases of the masticatory
      system; their symptoms are clicking, difficulty opening the mouth wide, ear pain,
      facial pain and headaches. The relationships among distress, emotional factors
      and TMD are well known. It was shown that patients with TMD have little awareness
      of their inner states and emotions, and it was found that those reporting oro
      facial pain presented higher alexithymia than did asymptomatic people. Other
      authors confirmed that alexithymia was higher in the painful TMD group than
      controls. This study was aimed to evaluate whether alexithymia and its components
      can be considered as predisposing factors for pain severity, poor health and
      greater social difficulties in patients with TMD. One hundred thirty-three
      patients received a diagnosis of TMD and completed the 20-item Toronto
      Alexithymia Scale. Multiple stepwise regressions showed that alexithymia and age
      explained 10% of the pain and 31% of poor health and also that alexithymia
      explained 7% of social difficulty. A direct comparison of patients with TMD based
      on alexithymia revealed a higher presence of pain in alexithymic patients with
      TMD than in those characterised by moderate or no alexithymia. In conclusion,
      alexithymia partly predicts pain, poor health and social difficulties in patients
      with TMD. Furthermore, alexithymic patients have more pain than those with
      moderate or low alexithymia. 

PMID- 23869942
TI  - Immunohistochemical analysis of ubiquilin-1 in the human hippocampus: association
      with neurofibrillary tangle pathology.
AB  - This post mortem immunohistochemical study examined the localization and
      distribution of ubiquilin-1 (UBL), a shuttle protein which interacts with
      ubiquitin and the proteasome, in the hippocampus from Alzheimer's disease (AD)
      dementia cases, and age-matched cases without dementia. In Braak stages 0-I-II
      cases, UBL immunoreactivity was detected in a dense fiber network in the
      neuropil, and in the cell cytoplasm and nucleoplasm of neurons in Cornu Ammonis
      (CA) fields and dentate gyrus granular neurons. In Braak stages III-IV and V-VI
      cases, UBL immunoreactivity was reduced in the neuropil and in the cytoplasm of
      the majority of CA1 neurons; some CA1 pyramidal neurons and the majority of CA2/3
      pyramidal, CA4 multipolar, and dentate granular neurons had markedly increased
      UBL immunoreactivity in the nucleoplasm. Dual immunofluorescence analysis of UBL
      and antibody clone AT8 revealed co-localization most frequently in CA1 pyramidal
      neurons in Braak stage III-IV and V-VI cases. Further processing using the pan
      amyloid marker X-34 revealed prominent UBL/X-34 dual labeling of extracellular
      NFT confined to the CA1/subiculum in Braak stage V-VI cases. Our results
      demonstrate that in AD hippocampus, early NFT changes are associated with
      neuronal up-regulation of UBL in nucleoplasm, or its translocation from the
      cytoplasm to the nucleus. The perseverance of UBL changes in CA2/3, CA4 and
      dentate gyrus, generally considered as more resistant to NFT pathology, but not
      in the CA1, may mark a compensatory, potentially protective response to increased
      tau phosphorylation in hippocampal neurons; the failure of such a response may
      contribute to neuronal degeneration in end-stage AD.

PMID- 23869945
TI  - Cognitive representations of peripheral neuropathy and self-reported foot-care
      behaviour of people at high risk of diabetes-related foot complications.
AB  - AIM: The aim of this study was to explore the cognitive representations of
      peripheral neuropathy and self-reported foot-care behaviour in an Australian
      sample of people with diabetes and peripheral neuropathy. METHODS: This cross
      sectional study was undertaken with 121 participants with diabetes and peripheral
      neuropathy. Cognitive representations of peripheral neuropathy were measured by
      the Patients' Interpretation of Neuropathy questionnaire and two aspects of self
      foot-care behaviour were measured using a self-report questionnaire. Hierarchical
      cluster analysis using the average linkage method was used to identify distinct
      illness schemata related to peripheral neuropathy. RESULTS: Three clusters of
      participants were identified who exhibited distinct illness schemata related to
      peripheral neuropathy. One cluster had more misperceptions about the nature of
      peripheral neuropathy, one cluster was generally realistic about the nature of
      their condition and the final cluster was uncertain about their condition. The
      cluster with high misperceptions of their condition undertook more potentially
      damaging foot-care behaviours than the other clusters (F = 4.98; P < 0.01).
      CONCLUSIONS: People with diabetes and peripheral neuropathy have different
      illness schemata that may influence health-related behaviour. Education aimed at
      improving foot-care behaviour and foot-health outcomes should be tailored to
      specific illness schemata related to peripheral neuropathy.

PMID- 23869946
TI  - Mycobacterium tuberculosis DNA gyrase possesses two functional GyrA-boxes.
AB  - In contrast with most bacteria which possess two type II topoisomerases
      (topoisomerase IV and DNA gyrase), Mycobacterium tuberculosis possesses only one,
      DNA gyrase, which is functionally a hybrid enzyme. Functional differences between
      the two type IIA topoisomerases are thought to be specified by a CTD (C-terminal
      DNA-binding domain), which controls DNA recognition. To explore the molecular
      mechanism responsible for the hybrid functions of the M. tuberculosis DNA gyrase,
      we conducted a series of sequence analyses and structural and biochemical
      experiments with the isolated GyrA CTD and the holoenzyme. Although the CTD
      displayed a global structure similar to that of bona fide GyrA and ParC
      paralogues, it harbours a second key motif similar in all respects to that of the
      conserved GyrA-box sequence motif. Biochemical assays showed that the GyrA-box is
      responsible for DNA supercoiling, whereas the second GyrA-box-l (GyrA-box-like
      motif) is responsible for the enhanced decatenation activity, suggesting that the
      mechanistic originality of M. tuberculosis DNA gyrase depends largely on the
      particular DNA path around the CTD allowed for by the presence of GyrA-box-l. The
      results of the present study also provide, through phylogenetic exploration of
      the entire Corynebacterineae suborder, a new and broader insight into the
      functional diversity of bacterial type IIA topoisomerases. 

PMID- 23869947
TI  - A century of indicator dilution technique.
AB  - This review imparts the history and the present status of the indicator dilution
      technique with quantitative bolus injection. The first report on flow measurement
      with this technique appeared 100 years ago. In 1928, the use of intravascular
      dyes made possible a widespread application in animals and human during the next
      decades. Multiple indicators, radioactive tracers, inlet-outlet detection and
      residue detection were introduced in the 1950s and 1960s, and refined along with
      the development of indicator kinetics. From the 1970s, a wide clinical use in the
      study of heart, brain, lungs, liver and kidneys developed, and powerful computers
      in the 1980s and 1990s accorded the technique a new dimension. Today, the
      indicator dilution technique, on one hand, is applied in the same way as 100
      years ago, on the other hand it forms the basis of quantitative SPECT, positron
      emission tomography, and dynamic MR scans. The technique still undergoes
      refinement and elaboration as a lasting concept with a high potential for further
      development. 

PMID- 23869948
TI  - Roads as a threat to the Serengeti ecosystem.

PMID- 23869949
TI  - Differential responses of migratory locusts to systemic RNA interference via
      double-stranded RNA injection and feeding.
AB  - The migratory locust, Locusta migratoria, is one of the most destructive
      agricultural pests and has been widely used as a model system for insect
      physiology, neurobiology and behavioural research. In the present study, we
      investigated the effects of RNA interference (RNAi) using two delivery methods
      for double-stranded RNA (dsRNA) molecules, namely, injection and feeding, to
      develop a potential new pest control strategy. Our results showed that locusts
      have a sensitive and systemic response to the injection of dsRNAs in a dose
      dependent manner, but do not respond to the feeding of dsRNAs. Further
      experiments suggested that the ineffectiveness of dsRNA feeding was attributable
      to the rapid degradation of dsRNA, which was probably induced by nuclease enzymes
      in the locust midgut. Moreover, we identified almost all the homologous genes
      involved in the endocytosis-mediated dsRNA uptake from the locust genome, which
      provided possible clues regarding the dsRNA uptake mechanisms from the intestine
      to the midgut epithelium. These findings reveal the differential response models
      of fourth instar locust nymphs to dsRNA delivery methods, contribute to the
      current understanding of insect RNAi mechanisms and provide important information
      for the further application of RNAi as a genetic tool and pest control strategy. 

PMID- 23869950
TI  - Time-resolved and mechanistic study of the photochemical uncaging reaction of the
      o-hydroxycinnamic caged compound.
AB  - The o-hydroxycinnamic derivatives represent efficient caged compounds that can
      realize quantification of delivery upon uncaging, but there has been lack of time
      resolved and mechanistic studies. We used time-resolved infrared (TRIR)
      spectroscopy to investigate the photochemical uncaging dynamics of the prototype
      o-hydroxycinnamic compound, (E)-3-(2-hydroxyphenyl)-acrylic acid ethyl ester
      (HAAEE), leading to coumarin and ethanol upon uncaging. Taking advantage of the
      specific vibrational marker bands and the IR discerning capability, we have
      identified and distinguished two key intermediate species, the cis-isomers of
      HAAEE and the tetrahedral intermediate, in the transient infrared spectra, thus
      providing clear spectral evidence to support the intramolecular nucleophilic
      addition mechanism following the trans-cis photoisomerization. Moreover, the
      product yields of coumarin upon uncaging were observed to be greatly affected by
      the solvent polarity, suppressed in CH2Cl2 but enhanced in D2O/CH3CN with the
      increasing volume ratio of D2O. The highly solvent-dependent behavior indicates
      E1 elimination of the tetrahedral intermediate to give rise to the final uncaging
      product coumarin. The photorelease rate of coumarin was directly characterized
      from TRIR (3.6 * 10(6) s(-1)), revealing the promising application of such o
      hydroxycinnamic compound in producing fast alcohol jumps. The TRIR results
      provide the first time-resolved detection and thus offer direct dynamical
      information about this photochemical uncaging reaction. 

PMID- 23869951
TI  - Clinical usefulness of intraductal ultrasonography for the management of acute
      biliary pancreatitis.
AB  - BACKGROUND AND AIM: Identifying a bile duct (BD) stone in patients with acute
      biliary pancreatitis (ABP) is important for the management and prevention of
      recurrent attack of pancreatitis. However, small BD stones may not be detected on
      endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was
      to prospectively evaluate the usefulness of intraductal ultrasonography (IDUS) in
      patients suspected to have ABP but with no evidence of choledocholithiasis on
      ERCP. METHODS: A total 92 patients suspected with ABP without evidence of BD
      stones on imaging studies including ERCP were enrolled. Wire-guided IDUS was
      performed during ERCP in all patients. Stones or sludge detected by IDUS were
      confirmed after endoscopic sphincterotomy (EST) and extraction. If IDUS finding
      was negative, then we swept the BD with a balloon catheter and/or basket without
      EST. After endoscopic management, comparison between IDUS and endoscopic finding
      was carried out to determine the diagnostic accuracy of IDUS. RESULTS: Among the
      92 patients, IDUS revealed BD stones in 33 (35.9%). All 33 patients' stones were
      confirmed by endoscopic visualization after EST and BD exploration. During the
      mean follow up of 24 months, recurrent pancreatitis did not occur in 90 of 92
      patients (97.9%) with ABP after endoscopic treatment according to the IDUS
      findings. CONCLUSIONS: IDUS improves diagnostic accuracy for the detection of
      clinically occult BD stones in patients suspicious ABP. IDUS-guided endoscopic
      management for patients with ABP can avoid unnecessary EST and help prevent
      recurrent pancreatitis.

PMID- 23869953
TI  - Fine needle aspiration cytology of soft tissue perineurioma: a case report.

PMID- 23869952
TI  - Maternal responsivity in mothers of young children with Down syndrome.
AB  - OBJECTIVE: The purpose of this study was to examine maternal responsivity and
      directive behaviors in mothers of children with Down syndrome (DS). METHODS:
      Participants included 22 mothers with a young child with DS compared to 22
      mothers of chronologically age-matched typically developing (TD) children using a
      cross-sectional design. The dyads participated in videotaped structured
      activities that were coded for responsive and directive behaviors. RESULTS:
      RESULTS indicated that the mothers of children with DS used a more facilitative
      style with the older children while these behaviors decreased with older children
      with TD; one directive behavior, request for behavioral comply, increased with
      the older children with DS. CONCLUSION: The mothers of children with DS adapted
      their parenting style to be facilitative of their children's linguistic
      development.

PMID- 23869954
TI  - Imbalance between circulating CD4+ regulatory T and conventional T lymphocytes in
      patients with HBV-related acute-on-chronic liver failure.
AB  - BACKGROUND & AIMS: The important pathophysiological role of immune dysfunction,
      especially innate immune dysfunction in patients with acute-on-chronic liver
      failure (ACLF), has been investigated in recent years, but dysregulation of
      adaptive immunity remains poorly elucidated. The aim of this study was to (i)
      determine the CD3(+) T-lymphocyte count and the balance between CD4(+) regulatory
      T (Tregs) and conventional T cells (Tconv) in hepatitis B virus (HBV)-related
      ACLF patients; (ii) analyse the frequencies of Tregs subpopulations; and (iii)
      assess the suppressive potency of CD4(+) Tregs and each fraction. METHODS: We
      enrolled 20 HBV-ACLF patients, 10 septic shock subjects, 20 chronic hepatitis B
      (CHB) patients and 20 healthy volunteers (HC). Based on flow cytometry, we
      performed the absolute counting of circulating T lymphocytes and phenotyping of
      CD4(+) Tregs and quantified the effects of Tregs and each subpopulation on Tconv
      proliferation by CFSE staining. RESULTS: Compared with CHB patients and HC, we
      observed an equal reduction in peripheral T subsets in HBV-ACLF and septic shock
      subjects; the number of CD4(+) Tregs remained unchanged and the Tconv count
      declined, promoting elevation of the Treg-to-Tconv ratio. The frequencies of Treg
      II and -III were elevated in HBV-ACLF. Functional studies showed that the
      suppressive capacity of Tregs was preserved in the HBV-ACLF group and Treg-II
      came first. CONCLUSIONS: Similar to septic shock subjects, in HBV-ACLF patients
      there exists a reduction in CD4(+) T lymphocytes, predominantly CD4(+) Tconv, and
      the development of suppressive CD4(+) Tregs greatly prevails over Tconv,
      constituting important characteristics of adaptive immune dysfunction of HBV
      ACLF.

PMID- 23869955
TI  - The in vitro efficacy of antimicrobial agents against the pathogenic free-living
      amoeba Balamuthia mandrillaris.
AB  - The free-living amoeba Balamuthia mandrillaris causes usually fatal encephalitis
      in humans and animals. Only limited studies have investigated the efficacy of
      antimicrobial agents against the organism. Assay methods were developed to assess
      antimicrobial efficacy against both the trophozoite and cyst stage of B.
      mandrillaris (ATCC 50209). Amphotericin B, ciclopirox olamine, miltefosine,
      natamycin, paromomycin, pentamidine isethionate, protriptyline, spiramycin,
      sulconazole and telithromycin had limited activity with amoebacidal levels of >
      135-500 MUM. However, diminazene aceturate (Berenil((r)) ) was amoebacidal at 7.8
      MUM and 31.3-61.5 MUM for trophozoites and cysts, respectively. Assays for
      antimicrobial testing may improve the prognosis for infection and aid in the
      development of primary selective culture isolation media. 

PMID- 23869956
TI  - Evaluation of the effectiveness of semen storage and sperm purification methods
      for spermatozoa transcript profiling.
AB  - Different semen storage and sperm purification methods may affect the integrity
      of isolated spermatozoal RNA. RNA-Seq was applied to determine whether semen
      storage methods (pelleted vs. liquefied) and somatic cell lysis buffer (SCLB) vs.
      PureSperm (PS) purification methods affect the quantity and quality of sperm RNA.
      The results indicate that the method of semen storage does not markedly impact
      RNA profiling whereas the choice of purification can yield significant
      differences. RNA-Seq showed that the majority of mitochondrial and mid-piece
      associated transcripts were lost after SCLB purification, which indicated that
      the mid-piece of spermatozoa may have been compromised. In addition, the number
      of stable transcript pairs from SCLB-samples was less than that from the PS
      samples. This study supports the view that PS purification better maintains the
      integrity of spermatozoal RNAs. 

PMID- 23869957
TI  - Mutational breeding and genetic engineering in the development of high grain
      protein content.
AB  - Cereals are the most important crops in the world for both human consumption and
      animal feed. Improving their nutritional values, such as high protein content,
      will have significant implications, from establishing healthy lifestyles to
      helping remediate malnutrition problems worldwide. Besides providing a source of
      carbohydrate, grain is also a natural source of dietary fiber, vitamins,
      minerals, specific oils, and other disease-fighting phytocompounds. Even though
      cereal grains contain relatively little protein compared to legume seeds, they
      provide protein for the nutrition of humans and livestock that is about 3 times
      that of legumes. Most cereal seeds lack a few essential amino acids; therefore,
      they have imbalanced amino acid profiles. Lysine (Lys), threonine (Thr),
      methionine (Met), and tryptophan (Trp) are among the most critical and are a
      limiting factor in many grain crops for human nutrition. Tremendous research has
      been put into the efforts to improve these essential amino acids. Development of
      high protein content can be outlined in four different approaches through
      manipulating seed protein bodies, modulating certain biosynthetic pathways to
      overproduce essential and limiting amino acids, increasing nitrogen relocation to
      the grain through the introduction of transgenes, and exploiting new genetic
      variance. Various technologies have been employed to improve protein content
      including conventional and mutational breeding, genetic engineering, marker
      assisted selection, and genomic analysis. Each approach involves a combination of
      these technologies. Advancements in nutrigenomics and nutrigenetics continue to
      improve public knowledge at a rapid pace on the importance of specific aspects of
      food nutrition for optimum fitness and health. An understanding of the molecular
      basis for human health and genetic predisposition to certain diseases through
      human genomes enables individuals to personalize their nutritional requirements.
      It is critically important, therefore, to improve grain protein quality. Highly
      nutritious grain can be tailored to functional foods to meet the needs for both
      specific individuals and human populations as a whole.

PMID- 23869958
TI  - Psychometrics of the neonatal oral motor assessment scale.
AB  - AIM: To establish the psychometrics of the Neonatal Oral Motor Assessment Scale
      (NOMAS). METHOD: In this prospective cohort study of 75 preterm infants (39
      females, 36 males) born at or before 30 weeks gestation (mean gestational age
      26.56 wks, SD 1.90, range 23-30 wks; mean birthweight 967.33 g, SD 288.54, range
      480-2240), oral feeding was videotaped before discharge from the neonatal
      intensive care unit (NICU). The NOMAS was used to classify feeding as normal,
      disorganized, or dysfunctional. Neurobehavior was assessed at term equivalent,
      and infants underwent magnetic resonance imaging. Children returned for
      developmental testing at 2 years corrected age. Associations between NOMAS scores
      and (1) neurobehavior; (2) cerebral injury and metrics; and (3) developmental
      outcome were investigated using chi(2) -analyses, t-tests, and linear regression.
      For reliability, six certified NOMAS evaluators rated five randomly selected
      NOMAS recordings and re-scored them 2 weeks later in a second randomized order.
      Reliability was calculated with Cohen's kappa statistics. RESULTS: Dysfunctional
      NOMAS scores were associated with lower Dubowitz scores [t=-2.14; mean difference
      -2.32 (95% confidence interval [CI] -0.157 to -4.49); p=0.036], higher stress on
      the NICU Network Neurobehavioral Scale (t=2.61; mean difference 0.073 [95% CI
      0.017-0.129]; p=0.0110), and decreased transcerebellar diameter (t=-2.22; mean
      difference -2.04 [CI=-3.89 to -0.203]; p=0.03). No significant associations were
      found between NOMAS scores and 2-year outcome. INTERPRETATION: Some concurrent
      validity was established with associations between NOMAS scores and measures of
      infant behavior and cerebral structure. The NOMAS did not show predictive
      validity in this study of preterm infants at high risk of developmental delay.
      Reliability was variable and suboptimal.

PMID- 23869960
TI  - Novel antibacterial silver-silica surface coatings prepared by chemical vapour
      deposition for infection control.
AB  - AIMS: Environmental contamination plays an important role in the transmission of
      infections, especially healthcare-associated infections. Disinfection transiently
      reduces contamination, but surfaces can rapidly become re-contaminated.
      Antimicrobial surfaces may partially overcome that limitation. The antimicrobial
      activity of novel surface coatings containing silver and silica prepared using a
      flame-assisted chemical vapour deposition method on both glass and ceramic tiles
      was investigated. METHODS AND RESULTS: Antimicrobial activity against a variety
      of bacteria including recent clinical isolates was investigated based on the BS
      ISO 22196:2007 Plastics--Measurement of antibacterial activity on plastics
      surfaces, British Standards Institute, London, method. Activity on natural
      contamination in an in use test in a toilet facility was also determined.
      Activity on standard test strains gave a log10 reduction of five after 1-4 h. The
      hospital isolates were more resistant, but MRSA was reduced by a log10 reduction
      factor of >5 after 24 h. Activity was maintained after simulated ageing and
      washing cycles. Contamination in situ was reduced by >99.9% after 4 months.
      Activity was inhibited by protein, but, although this could be overcome by
      increasing the amount of silver in the films, this reduced the hardness of the
      coating. CONCLUSIONS: The coatings had a good activity against standard test
      strains. Clinical isolates were killed more slowly but were still sensitive. The
      optimum composition for use therefore needs to be a balance between activity and
      durability. SIGNIFICANCE AND IMPACT OF THE STUDY: The coatings may have
      applications in health care by maintaining a background antimicrobial activity
      between standard cleaning and disinfection regimes. They may also have
      applications in other areas where reduction in microbial contamination is
      important, for example, in the food industry.

PMID- 23869961
TI  - Practical considerations for the interpretation of microbial testing results
      based on small numbers of samples.
AB  - While adequate, statistically designed sampling plans should be used whenever
      feasible, inference about the presence of pathogens in food occasionally has to
      be made based on smaller numbers of samples. To help the interpretation of such
      results, we reviewed the impact of small sample sizes on pathogen detection and
      prevalence estimation. In particular, we evaluated four situations commonly
      encountered in practice. The first two examples evaluate the combined impact of
      sample size and pathogen prevalence (i.e., fraction of contaminated food items in
      a given lot) on pathogen detection and prevalence estimation. The latter two
      examples extend the previous example to consider the impact of pathogen
      concentration and imperfect test sensitivity. The provided examples highlight the
      difficulties of making inference based on small numbers of samples, and emphasize
      the importance of using appropriate statistical sampling designs whenever
      possible.

PMID- 23869962
TI  - Emergence of a multidrug-resistant (ASSuTTm) strain of Salmonella enterica
      serovar Typhimurium DT120 in England in 2011 and the use of multiple-locus
      variable-number tandem-repeat analysis in supporting outbreak investigations.
AB  - In summer 2011, two outbreaks of a unique, multidrug-resistant strain of
      Salmonella enterica serovar Typhimurium phage type 120 (DT120) occurred mainly in
      the Midlands, England. The first outbreak occurred among guests attending a
      wedding in July 2011 ('Wedding outbreak'), followed by a more geographically
      dispersed outbreak in August and September 2011 ('Midlands outbreak'). Fifty-one
      cases were confirmed. Detailed epidemiological and environmental health
      investigations suggested that pork was the most likely source of both outbreaks.
      All human samples and one pork sample showed the specific multiple-locus variable
      number tandem-repeat analysis (MLVA) profile 3-11-12-NA-0211, with at most two
      loci variations. Trace-back investigations suggested a link to a butcher's shop
      and a pig farm in the East Midlands. The investigations highlight the utility of
      molecular analysis (MLVA) in supporting epidemiological investigations of
      outbreaks caused by S. Typhimurium DT120. Safe handling and cooking of pork by
      food business operators and consumers are key interventions to prevent future
      outbreaks.

PMID- 23869963
TI  - Matrix for assessment of activities and participation: Measuring functioning
      beyond diagnosis in young children with disabilities.
AB  - OBJECTIVE: (i) To study the functioning patterns of young children with
      disabilities compared with typically developing children, using a new ICF-CY
      based tool--the Matrix for Assessment of Activities and Participation; (ii) study
      the factors that predict these functioning patterns. METHODS: The MAAP tool was
      administered to three groups of children: (i) with autism, (ii) with other types
      of disabilities and (iii) typically developing. RESULTS: Cluster analysis showed
      that children group according to the severity of their functioning profile and
      not according to the diagnostic category in which they were classified. Multiple
      regression analysis showed that a model comprising the environmental factors and
      the level of engagement in different routines of the child is a good predictor of
      these children's functioning patterns. CONCLUSION: These results support a
      functional approach to disability instead of the traditional medical model
      approach, underlining the role of engagement and environment in determining
      functioning.

PMID- 23869964
TI  - Orbital inflammation secondary to a delayed hypersensitivity reaction to sub
      Tenon's hyaluronidase.
AB  - We report a rare case of a delayed orbital inflammation with raised intraocular
      pressure as a result of hyluronidase allergy following sub-Tenon's anaesthesia.
      Here, we have shown evidence to prove the orbital inflammation to be an allergic
      response to hyluronidase with a skin patch test. This is the first case to our
      knowledge of a delayed hypersensitivity reaction to sub-Tenon's hyluronidase
      comprising of an initial exposure to hyluronidase in the fellow eye with no
      subsequent allergic response, but with a subsequent delayed reaction to
      hyluronidase during a second eye cataract surgery. This case demonstrates
      hyaluronidase allergy should be considered as a differential diagnosis among
      patients presenting with acute post-operative orbital inflammation, even if there
      is a history of previous exposure to hyaluronidase in the fellow eye with no
      subsequent allergic response.

PMID- 23869966
TI  - Ernie Mazzaferri: The Breadth of His Influence.
AB  - NA.

PMID- 23869965
TI  - CH-pi "T-shape" interaction with histidine explains binding of aromatic
      galactosides to Pseudomonas aeruginosa lectin LecA.
AB  - The galactose specific lectin LecA mediates biofilm formation in the
      opportunistic pathogen P. aeruginosa . The interaction between LecA and aromatic
      beta-galactoside biofilm inhibitors involves an intermolecular CH-pi T-shape
      interaction between C(epsilon1)-H of residue His50 in LecA and the aromatic ring
      of the galactoside aglycone. The generality of this interaction was tested in a
      diverse family of beta-galactosides. LecA binding to aromatic beta-galactosides
      (KD ~ 8 MUM) was consistently stronger than to aliphatic beta-galactosides (KD ~
      36 MUM). The CH-pi interaction was observed in the X-ray crystal structures of
      six different LecA complexes, with shorter than the van der Waals distances
      indicating productive binding. Related XH/cation/pi-pi interactions involving
      other residues were identified in complexes of aromatic glycosides with a variety
      of carbohydrate binding proteins such as concanavalin A. Exploiting such
      interactions might be generally useful in drug design against these targets. 

PMID- 23869967
TI  - Isolation of lesbian, gay, bisexual and transgender youth: a dimensional concept
      analysis.
AB  - AIM: To present the findings of a dimensional analysis of isolation in the
      context, and from the perspective, of lesbian, gay, bisexual and transgender
      youth. BACKGROUND: Lesbian, gay, bisexual and transgender youth are often at
      greater risk for negative health outcomes compared with heterosexual youth.
      Isolation is one risk factor cited throughout the literature; however, the
      concept is complicated and has many uses and thus warrants clarification. DESIGN:
      Concept Analysis. DATA SOURCES: Sources comprise 35 English language research
      articles retrieved from CINAHL and EBSCOHost (1987-2012). METHODS: A dimensional
      concept analysis was undertaken to analyse how the concept, isolation, is
      socially constructed. RESULTS: This dimensional analysis revealed five socially
      constructed dimensions and four sub-dimensions. These findings indicate that
      there is substantial variability in the concept of isolation. These differences
      and variations are most notably observed in the 20 articles (57%) that had more
      than one dimension. Although some of these articles were explicit with the
      different meanings and use of the concept, most of the papers had wide
      variability in the use and meaning of the concept. CONCLUSION: The
      disproportionately greater physical and mental health disparities between
      lesbian, gay, bisexual and transgender and heterosexual youth are a signal to
      conduct more research to clarify the concept of isolation, to develop
      instrumentation to identify at-risk youth and to explore predictors and
      consequences of isolation. Nurses and others can lead the way in translating this
      knowledge into strategies that will improve the health and lives of these young
      people.

PMID- 23869968
TI  - Salmonella enterica delivers its genotoxin through outer membrane vesicles
      secreted from infected cells.
AB  - Cytolethal-distending toxins (CDTs) belong to a family of DNA damage inducing
      exotoxins that are produced by several Gram-negative bacteria. Salmonella
      enterica serovar Typhi expresses its CDT (named as Typhoid toxin) only in the
      Salmonella-containing vacuole (SCV) of infected cells, which requires its export
      for cell intoxication. The mechanisms of secretion, release in the extracellular
      space and uptake by bystander cells are poorly understood. We have addressed
      these issues using a recombinant S. Typhimurium strain, MC71-CDT, where the genes
      encoding for the PltA, PltB and CdtB subunits of the Typhoid toxin are expressed
      under control of the endogenous promoters. MC71-CDT grown under conditions that
      mimic the SCV secreted the holotoxin in outer membrane vesicles (OMVs).
      Epithelial cells infected with MC71-CDT also secreted OMVs-like vesicles. The
      release of these extracellular vesicles required an intact SCV and relied on
      anterograde transport towards the cellular cortex on microtubule and actin
      tracks. Paracrine internalization of Typhoid toxin-loaded OMVs by bystander cells
      was dependent on dynamin-1, indicating active endocytosis. The subsequent
      induction of DNA damage required retrograde transport of the toxin through the
      Golgi complex. These data provide new insights on the mode of secretion of
      exotoxins by cells infected with intracellular bacteria.

PMID- 23869969
TI  - An access technology delivery protocol for children with severe and multiple
      disabilities: a case demonstration.
AB  - OBJECTIVE: This study applied response efficiency theory to create the Access
      Technology Delivery Protocol (ATDP), a child and family-centred collaborative
      approach to the implementation of access technologies. METHODS: We conducted a
      descriptive, mixed methods case study to demonstrate the ATDP method with a 12
      year-old boy with no reliable means of access to an external device. Evaluations
      of response efficiency, satisfaction, goal attainment, technology use and
      participation were made after 8 and 16 weeks of training with a custom smile
      based access technology. RESULTS: At the 16 week mark, the new access technology
      offered better response quality; teacher satisfaction was high; average
      technology usage was 3-4 times per week for up to 1 h each time; switch
      sensitivity and specificity reached 78% and 64%, respectively, and participation
      scores increased by 38%. CONCLUSION: This case supports further development and
      testing of the ATDP with additional children with multiple or severe
      disabilities.

PMID- 23869970
TI  - Fecal transplantation for recurrent Clostridium difficile infection in older
      adults: a review.
AB  - Recurrent Clostridium difficile infection (CDI) is a common nosocomial infection
      that has a large effect on morbidity and quality of life in older adults in
      hospitals and long-term care facilities. Because antibiotics are often
      unsuccessful in curing this disease, fecal transplantation has emerged as a
      second-line therapy for treatment of recurrent CDI. A comprehensive literature
      search of PubMed, Embase, and Web of Science regarding fecal transplantation for
      CDI was performed to further evaluate the efficacy and side effects of this
      promising therapy in older adults. Data were extracted from 10 published articles
      from 1984 to the present that met inclusion criteria, including nine open-label
      reports and one randomized controlled trial. Baseline characteristics and
      outcomes of individuals undergoing fecal transplantation and effects of fecal
      transplantation on the fecal microflora were reviewed. Methods of fecal
      transplantation and donor selection were reviewed. Fecal transplantation was
      performed in 115 individuals aged 60 to 101, with a female predominance. CDI cure
      was achieved in 103 (89.6%) individuals over a follow-up period of 2 months to 5
      years (mean 5.9 months). There was no significant difference in cure rate between
      older and younger participants in included studies. Most failed transplantation
      occurred in individuals infected with the aggressive NAP1/027 strain of C.
      difficile. Microbiological studies of fecal biodiversity before and after fecal
      transplantation demonstrated greater bacterial diversity and shift in flora
      species to resemble donor flora after transplantation that correlated with
      clinical remission. Fecal transplantation provides a safe and durable cure for
      older adults with recurrent CDI.

PMID- 23869971
TI  - Multidrug-resistant Pseudomonas aeruginosa: a case of pyelonephritis and herbal
      therapy.
AB  - Multidrug-resistant Pseudomonas aeruginosa, which was only susceptible to
      colistin, was isolated from the urine of a patient with pyelonephritis. The
      isolates were confirmed as class A Extended-spectrum-beta-lactamase-producing
      isolates. A blaBEL allele was detected by multiplex polymerase chain reaction.
      The organisms were identified as ST235, serotype O11. Chinese herbal decoction
      was orally administered. The patient returned 8 days later with relief of
      symptoms. No P. aeruginosa was isolated from two urine samples taken after 1 week
      and 2 weeks from the end of herbal therapy. The case supports the notion that
      these Chinese herbs are useful in treating pyelonephritis caused by multidrug
      resistant P. aeruginosa. Chinese herbal medicine has allowed another choice of
      treatment.

PMID- 23869972
TI  - Triplet sensitization in an anionic poly(phenyleneethynylene) conjugated
      polyelectrolyte by cationic iridium complexes.
AB  - We describe a systematic study of triplet sensitization in a
      poly(phenyleneethynylene) conjugated polyelectrolyte (CPE) in methanol solution
      by using a series of three cationic iridium complexes with varying triplet
      energy. The cationic iridium complexes bind to the anionic CPE by ion-pairing,
      leading to singlet state quenching of the polymer, and allowing for efficient
      back-transfer of triplet excitation energy to the polymer. Efficient (amplified
      quenching) of the polymer's fluorescence is observed for each iridium complex,
      with Stern-Volmer quenching constants in excess of 10(5) M(-1). Triplet
      sensitization is confirmed for two of the iridium complexes by monitoring the
      relative yield of the CPE triplet state by transient absorption spectroscopy. One
      of the iridium complexes does not sensitize the CPE triplet, and consideration of
      the energies of the three complexes allows us to bracket the triplet energy of
      the CPE within the range 1.95-2.26 eV. 

PMID- 23869973
TI  - Phytotoxicity of new furan-derived aminophosphonic acids, N-aryl furaldimines and
      5-nitrofuraldimine.
AB  - The aim of this work was to synthesize selected furaldimines and their
      aminophosphonic derivatives and evaluation the phytotoxicity of new obtained
      products according to OECD 208 Guideline. Four Schiff bases, N-furfurylidene-p
      anisidine (1a), N-furfurylidene-p-toluidine (1b), N-furfurylidene-benzhydrylamine
      (1c), and N-(2-nitrofurfurylidene)-p-toluidine (1d) were synthesized and three
      new furan-derived N-substituted aminomethylphosphonic acids, namely: 2-furyl N-(p
      methoxyphenyl)-aminomethylphosphonic acid (2a), 2-furyl N-(p-methylphenyl)
      aminomethylphosphonic acid (2b) and 2-furyl N-(diphenylmethyl)
      aminomethylphosphonic acid (2c) were synthesized by the addition of in situ
      generated bis-(trimethylsilyl) phosphite to azomethine bond of corresponding
      Schiff bases 1a-c. Three Schiff bases 1a-b and 1d as well as all three
      aminophosphonic acids 2a-c were analyzed in regard with their phytotoxicity
      toward two plants, radish (Raphanus sativus) and oat (Avena sativa). It has been
      found that tested N-furfurylidene-p-anisidine (1a), N-(2-nitrofurfurylidene)-p
      toluidine (1d) and aminophosphonic acids 2a-c are toxic for selected plants. N
      furfurylidene-p-toluidine (1b) did not show any ecotoxicological impact in used
      plant growth test.

PMID- 23869974
TI  - Protracted low-dose radiation priming and response of liver to acute gamma and
      proton radiation.
AB  - This study evaluated liver from C57BL/6 mice irradiated with low-dose/low-dose
      rate (LDR) gamma-rays (0.01 Gy, 0.03 cGy/h), with and without subsequent exposure
      to acute 2 Gy gamma or proton radiation. Analyses were performed on day 56 post
      exposure. Expression patterns of apoptosis-related genes were strikingly
      different among irradiated groups compared with 0 Gy (p < 0.05). Two genes were
      affected in the Gamma group, whereas 10 were modified in the LDR + Gamma group.
      In Proton and LDR + Proton groups, there were six and 12 affected genes,
      respectively. Expression of genes in the Gamma (Traf3) and Proton (Bak1, Birc2,
      Birc3, Mcl1) groups was no longer different from 0 Gy control group when mice
      were pre-exposed to LDR gamma-rays. When each combined regimen was compared with
      the corresponding group that received acute radiation alone, two genes in the LDR
      + Gamma group and 17 genes in the LDR + Proton group were modified; greatest
      effect was on Birc2 and Nol3 (> 5-fold up-regulated by LDR + Protons). Oxygen
      radical production in livers from the LDR + Proton group was higher in LDR,
      Gamma, and LDR + Gamma groups (p < 0.05 vs. 0 Gy), but there were no differences
      in phagocytosis of E. coli. Sections stained with hematoxylin and eosin (H&E)
      suggested more inflammation, with and without necrosis, in some irradiated
      groups. The data demonstrate that response to acute radiation is dependent on
      radiation quality and regimen and that some LDR gamma-ray-induced modifications
      in liver response were still evident nearly 2 months after exposure.

PMID- 23869975
TI  - Autism severity as a predictor of inattention and impulsivity in toddlers.
AB  - OBJECTIVE: Evaluate how severity of autism spectrum disorder (ASD) symptoms
      predicts attention-deficit/hyperactivity disorder (ADHD) symptoms in atypically
      developing toddlers. METHOD: Parents/caregivers of 2300 atypically developing
      toddlers' ages 18-37 months were assessed about their children's behaviours using
      the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT) Part 1 and
      the inattention/impulsivity subscale of the BISCUIT-Part 2. RESULTS: ASD symptom
      severity was positively and significantly correlated with
      inattention/impulsivity, indicating that children with more severe symptoms of
      ASD tended to have higher scores on the measure of inattention/impulsivity, R(2)
      = 0.49, F (1, 2298) = 2234.72, p < 0.001. Additionally, ASD symptom severity
      significantly predicted inattention/impulsivity, beta = 0.70, t (2298) = 47.27, p
      < 0.001. CONCLUSIONS: ASD symptom severity predicts rates of ADHD symptoms in
      atypically developing toddlers. The implications of these findings are discussed
      in the context of other research.

PMID- 23869976
TI  - Magnetic resonance imaging findings of the abducens nerves in type 1 Duane's
      retraction syndrome.
AB  - PURPOSE: To investigate nervus abducens and extraocular mucles in patients with
      Type 1 Duane's retraction syndrome using high-definition magnetic resonance
      imaging. METHODS: The study included 10 patients with Type I Duane's retraction
      syndrome who underwent magnetic resonance imaging (MRI) of the brain and orbits.
      RESULTS: Overall, 10 cases were included in the study. There were seven women and
      three men. The mean age was 5.2 years (1-15 years). MRI of the abducens nerve was
      performed in all cases. Of the cases, the left eye was involved in eight cases,
      whereas the right eye was involved in two cases. There was no bilateral eye
      involvement. Among the 10 patients clinically diagnosed as Type 1 Duane's
      retraction syndrome, the abducens nerve could not be visualized in eight cases,
      whereas the nerve was hypoplastic in one case and bilateral abducens nerves were
      present in one case by MRI. The extraocular muscles were normal in all cases on
      T2 weighted coronal MRI of the orbits. CONCLUSION: Absence of abducens nerve and
      normal extraocular muscles was detected in patients with Type 1 Duane's
      retraction syndrome at the affected side.

PMID- 23869977
TI  - Cytogenetical study of a multifocal uveal melanoma.
AB  - Choroidal melanoma may arise de novo or transformed from a previously existing
      nevus. Modern cytogenetical techniques allow us to determine and classify the
      genetic aberrations of such tumors. We report a case of a 55-year-old man
      presenting a malignant transformation of a previously known choroidal nevus in
      his right eye. Nine years earlier, that same eye was treated with brachytherapy
      for a malignant melanoma. Enucleation was indicated followed by histopathological
      study as well as gene mutation analysis of the tumor cells. The second melanoma
      was anatomically independent from the first one, discarding the possibility of
      spreading. Cytogenetical study resulted in significant loss of the short arm of
      chromosome 1 and the long arm of chromosome 3. Only 21 cases of multiple uveal
      melanoma in the same eye are reported in the literature. To our knowledge this is
      the first cytogenetical report of one of such cases. It highlights the importance
      of follow-up in these patients, especially when risk factors like a choroidal
      naevus are present.

PMID- 23869978
TI  - Stand up and be counted.

PMID- 23869979
TI  - Juicy stories on female reproductive tissue development: coordinating the hormone
      flows.
AB  - In the past 20-30 years, developmental biologists have made tremendous progress
      in identifying genes required for the specification of individual cell types of
      an organ and in describing how they interact in genetic networks. In comparison,
      very little is known about the mechanisms that regulate tissue polarity and
      overall organ patterning. Gynoecia and fruits from members of the Brassicaceae
      family of flowering plants provide excellent model systems to study organ
      patterning and tissue specification because they become partitioned into distinct
      domains whose formation is determined by polarity establishment both at a
      cellular and whole tissue level. Interactions among key regulators of Arabidopsis
      gynoecium and fruit development have revealed a network of upstream transcription
      factor activities required for such tissue differentiation. Regulation of the
      plant hormone auxin is emerging as both an immediate downstream output and input
      of these activities, and here we aim to provide an overview of the current
      knowledge regarding the link between auxin and female reproductive development in
      plants. In this review, we will also demonstrate how available data can be
      exploited in a mathematical modeling approach to reveal and understand the
      feedback regulatory circuits that underpin the polarity establishment, necessary
      to guide auxin flows.

PMID- 23869980
TI  - Metabolic and reproductive effects of relatively low concentrations of
      beclomethasone dipropionate, a synthetic glucocorticoid, on fathead minnows.
AB  - Pharmaceuticals present in the aquatic environment could adversely affect aquatic
      organisms. Synthetic glucocorticoids (GC) are used in large quantities as anti
      inflammatory drugs and have been reported to be present in river water. In order
      to assess the impact of environmental concentrations of GCs, an in vivo
      experiment was conducted with adult fathead minnows. Fish were exposed to 0.1
      MUg/L, 1 MUg/L, or 10 MUg/L beclomethasone dipropionate (BCMD) via a flow-through
      system over a period of 21 days. Similar duplicate tanks served as control, with
      no chemical added. There was a concentration-related increase in plasma glucose
      concentration and a decrease in blood lymphocyte count. Induction of male
      secondary sexual characters and a decreasing trend in plasma vitellogenin (Vtg)
      concentrations in female fish were observed with increasing exposure
      concentration of BCMD. Expression profiles of selected genes (phosphoenolpyruvate
      carboxykinase - PEPCK, glucocorticoid receptor - GR, and Vtg) in liver also
      demonstrated concentration-related effects at all three tested concentrations.
      The results suggest that GCs could cause effects in lower micrograms per liter
      concentrations that could be environmentally relevant for total GCs present in
      the environment. Therefore, studies to determine the environmental concentrations
      of GCs and no effect concentrations are needed to assess if GCs pose a risk to
      the aquatic environment. 

PMID- 23869981
TI  - Two-hour post-load plasma glucose levels are associated with carotid intima-media
      thickness in subjects with normal glucose tolerance.
AB  - AIMS: Elevated post-load plasma glucose levels may increase the risk of
      cardiovascular disease, even when they are within the normoglycaemic range. We
      examined the association of carotid artery intima-media thickness, a marker of
      early atherosclerosis, with glycaemic variables, including post-load plasma
      glucose levels, in Japanese subjects with normal glucose tolerance. METHODS: The
      study participants were 663 Japanese subjects with normal glucose tolerance (565
      men, mean age 47 +/- 9 years) who underwent both a 75-g oral glucose tolerance
      test and carotid artery intima-media thickness measurement by B-mode
      ultrasonography during a health examination. Associations between maximal common
      carotid artery intima-media thickness and fasting plasma glucose, 1-h and 2-h
      plasma glucose during an oral glucose tolerance test, and HbA1c were examined.
      RESULTS: The carotid artery intima-media thickness gradually increased across the
      tertiles of 1-h plasma glucose, 2-h plasma glucose and HbA1c . In multiple linear
      regression analysis, 2-h plasma glucose (beta = 0.09, P = 0.012), as well as age,
      male gender, hypertension, dyslipidaemia, and current smoking were independent
      determinants of carotid artery intima-media thickness. In contrast, other
      glycaemic variables were not independent determinants of carotid artery intima
      media thickness. The carotid artery intima-media thickness in hypertensive
      subjects with the highest tertile of 2-h plasma glucose [0.70 (95% CI 0.64-0.76)
      mm] was significantly greater than in normotensive subjects, with the lowest
      tertile of 2-h plasma glucose [0.60 (95% CI 0.58-0.63) mm, P = 0.037], even after
      adjusting for the multiple potential confounders. CONCLUSIONS: The 2-h plasma
      glucose during an oral glucose tolerance test was positively and independently
      associated with carotid artery intima-media thickness in Japanese subjects with
      normal glucose tolerance. In particular, the combination of elevated 2-h plasma
      glucose and hypertension may contribute to an increased carotid artery intima
      media thickness.

PMID- 23869982
TI  - Measuring interpersonal continuity in high-frequency home healthcare services.
AB  - AIM: To provide a method for assessing the degree of interpersonal continuity
      adapted to context and to measure and assess the degree of interpersonal
      continuity for long-term recipients dependent on daily home health care.
      BACKGROUND: Interpersonal continuity is important to the quality of care for long
      term dependents. In high-frequency home healthcare services where patients
      receive daily care from many nurses or other health personnel over time,
      interpersonal continuity may be difficult to attain. DESIGN: A cross-sectional
      study with a descriptive design. METHODS: Information concerning 79 patients
      receiving long-term frequent care was collected during four weeks in a maximum
      variation sample of Norwegian municipalities, from January 2009-May 2010. We
      measured interpersonal continuity objectively using indices of dispersion and the
      next-day sequence of health personnel. For each measure, we computed the highest
      feasible level of continuity that could be attained in this home healthcare
      context given a standard shift plan. This level was then used as benchmark
      against which the actual level of continuity was assessed. RESULTS: Patients
      received on average 51 visits from a mean of 17 different carers during four
      weeks. The results revealed a low degree of interpersonal continuity in practice,
      far below what was feasible according to the benchmarks. CONCLUSION: High
      frequency home health care was characterized by interpersonal discontinuity, but
      with potential for improvement. Objective measures of interpersonal continuity,
      when the benchmark is adapted to the context, are useful tools for planning and
      surveying continuity of care.

PMID- 23869983
TI  - Community attitudes to remunerated blood donation in Australia: results from a
      national telephone survey.
AB  - BACKGROUND: Blood in Australia is sourced through voluntary, non-remunerated
      donations. With periodic shortages in supply, increasing demand for blood
      products and a donor base that is perceived to be unsustainable, remuneration has
      been proposed as a means to improve donation rates. OBJECTIVE: To examine
      community attitudes to remunerated blood donation in Australia. METHOD: A
      national random telephone survey of Australian adults age 18-70 was conducted (n
      = 1024). Associations were tested using a chi-square (chi(2)) test for linear
      distribution. RESULTS: Reimbursement for the cost of travel to donate blood was
      supported by more respondents (46%) than reimbursement for time (19%). Non-donors
      were more likely to support a payment compared to donors (P = 0.002). Twelve per
      cent of respondents thought they would be more likely to donate if remunerated
      while 10% thought they would be less likely. The majority (76%) thought that a
      payment would not change whether or not they would donate, while 85% thought that
      it would make other people more likely to donate. The average amount considered
      to be reasonable reimbursement was AU$30. CONCLUSION: Despite the common
      perception that other people would be motivated to donate blood with the
      introduction of a financial incentive, remuneration may provide minimal incentive
      in Australia and is unlikely to increase donor participation for the time being.

PMID- 23869984
TI  - Three-dimensional conformal radiation therapy alone or in combination with
      surgery for treatment of canine intracranial meningiomas.
AB  - Treatment protocols, treatment planning methods and tumour types in studies
      evaluating radiotherapy for canine brain tumours have been varied. This case
      series retrospectively evaluated the outcome of definitive, three-dimensional
      conformal radiation therapy (3D-CRT) as either a sole modality or as an adjuvant
      to surgery in 31 dogs diagnosed with meningioma by histopathology (n = 10) or
      cross-sectional imaging of the head (n = 21, assessed independently by two board
      certified radiologists). Prescribed dose ranged from 45 to 54 Gy in 2.5 to 3 Gy
      fractions. Median overall survival was 577 days (interquartile range = 272-829
      days; range = 30-1942 days) when all deaths were considered and 906 days
      (interquartile range = 336-912 days; range = 10 -1942 days) when only dogs dying
      due to meningioma were considered. No significant difference in survival time was
      detected for the defined clinical or imaging findings or between treatment with
      radiotherapy alone versus adjuvant radiotherapy, suggesting that 3D-CRT may be a
      viable alternative to surgery.

PMID- 23869986
TI  - Lymphatics and colorectal liver metastases: the case for sentinel node mapping.
AB  - BACKGROUND: Hepatic resection remains the treatment of choice for patients with
      colorectal liver metastases (CLM). Indications for hepatic resection have been
      extended to include extrahepatic lymph node groups, resulting in increased
      survival benefits. The identification of specific lymph pathways and involved
      nodes is necessary to support the development of guidelines for a more focused
      approach to the management of this disease. The feasibility of sentinel node
      mapping should be investigated to define specific lymphatic groups involved in
      CLM. METHODS: Scientific papers published from 1950 to 2012 were sought and
      extracted from the MEDLINE, PubMed and University of Melbourne databases.
      RESULTS: Several studies have reported microscopic lymph node involvement in 10
      15% of patients undergoing hepatic resection for CLM in which no macroscopic
      involvement was evident. In retrospect, over 80% of lymphadenectomies are proven
      unnecessary. Traditional imaging modalities have limited predictive value in
      detecting lymph node involvement. Sentinel node mapping has proved an extremely
      accurate tool in detecting lymph node involvement and can identify patients in
      whom lymphadenectomy may be beneficial. CONCLUSIONS: Current imaging techniques
      are inadequate to detect microscopic lymph node involvement in patients with
      resectable CLM. The use of sentinel node mapping is proposed to identify nodal
      groups involved and provide management strategies.

PMID- 23869987
TI  - Microsporidian diversity in soil, sand, and compost of the Pacific Northwest.
AB  - Microsporidia are intracellular parasites considered to be ubiquitous in the
      environment. Yet the true extent of their diversity in soils, sand, and compost
      remains unclear. We examined microsporidian diversity found in the common urban
      environments of soil, sand, and compost. We retrieved 22 novel microsporidian
      sequences and only four from described species. Their distribution was generally
      restricted to a single site and sample type. Surprisingly, one novel
      microsporidian showed a wide distribution, and high prevalence, as it was
      detected in five different compost samples and in soil samples collected over 200
      km apart. These results suggest that the majority of Microsporidia appear to have
      a narrow distribution. Our phylogenetic analysis indicated that the Microsporidia
      detected in this study include representatives from four of the five major
      microsporidian groups. Furthermore, the addition of our new sequences calls into
      question the cohesiveness of microsporidian clade II. These results highlight the
      importance of increasing our knowledge of microsporidian diversity to better
      understand the phylogenetic relationships and evolutionary history of this
      important group of emerging parasites. 

PMID- 23869988
TI  - Anti-programmed cell death-1 antibody as a new serological marker for type 1
      autoimmune hepatitis.
AB  - BACKGROUND AND AIM: Recently, the association of the dysfunction of programmed
      cell death (PD)-1 expressed on activated lymphocytes with the pathogenesis of
      autoimmune hepatitis (AIH) has been speculated. This study aimed to investigate
      the association of serum anti-PD-1 antibodies with clinical characteristics of
      type 1 AIH. METHODS: Serum samples before the initiation of prednisolone
      treatment were obtained from 52 type 1 AIH patients, 24 patients with drug
      induced liver injury (DILI), 30 patients with acute viral hepatitis (AVH), 11
      patients with primary sclerosing cholangitis (PSC), and 62 healthy volunteers.
      Titers of serum anti-PD-1 antibodies were measured by indirect enzyme-linked
      immunosorbent assay. The cutoff level was represented by a mean absorbance + 2
      standard deviations in healthy volunteers. RESULTS: Prevalence of serum anti-PD-1
      antibodies was 63% in type 1 AIH patients, 8% in DILI patients, 13% in AVH
      patients, 18% in PSC patients, and 3% in healthy volunteers. In type 1 AIH
      patients, titers of serum anti-PD-1 antibodies were correlated with serum levels
      of bilirubin (r = 0.31, P = 0.030) and alanine aminotransferase (r = 0.31, P =
      0.027) but not serum immunoglobulin G levels. Positivity for serum anti-PD-1
      antibodies was associated with the later normalization of serum alanine
      aminotransferase levels after the initiation of prednisolone and the disease
      relapse. CONCLUSIONS: Serum anti-PD-1 antibodies would be useful for the
      discrimination of type 1 AIH from DILI, AVH, and PSC as an auxiliary diagnostic
      marker. Furthermore, anti-PD-1 antibodies may be associated with clinical
      characteristics of type 1 AIH.

PMID- 23869989
TI  - Oxygen-dependent photochemistry and photophysics of "miniSOG," a protein-encased
      flavin.
AB  - Selected photochemical and photophysical parameters of flavin mononucleotide
      (FMN) have been examined under conditions in which FMN is (1) solvated in a
      buffered aqueous solution, and (2) encased in a protein likewise solvated in a
      buffered aqueous solution. The latter was achieved using the so-called "mini
      Singlet Oxygen Generator" (miniSOG), an FMN-containing flavoprotein engineered
      from Arabidopsis thaliana phototropin 2. Although FMN is a reasonably good
      singlet oxygen photosensitizer in bulk water (phiDelta = 0.65 +/- 0.04),
      enclosing FMN in this protein facilitates photoinitiated electron-transfer
      reactions (Type-I chemistry) at the expense of photosensitized singlet oxygen
      production (Type-II chemistry) and results in a comparatively poor yield of
      singlet oxygen (phiDelta = 0.030 +/- 0.002). This observation on the effect of
      the local environment surrounding FMN is supported by a host of spectroscopic and
      chemical trapping experiments. The results of this study not only elucidate the
      behavior of miniSOG but also provide useful information for the further
      development of well-characterized chromophores suitable for use as intracellular
      sensitizers in mechanistic studies of reactive oxygen species.

PMID- 23869990
TI  - Cerebral oedema is not responsible for motor or cognitive deficits in rats with
      hepatic encephalopathy.
AB  - BACKGROUND & AIMS: Low-grade cytotoxic oedema is considered a main contributor to
      the neurological (motor and cognitive) alterations in patients with hepatic
      encephalopathy (HE). This assumption is mainly based on studies with cultured
      astrocytes treated with very large ammonia concentrations or with animal models
      of acute liver failure with strong HE. However, the possible contribution of
      cerebral oedema (vasogenic or cytotoxic) to cognitive or motor alterations in
      chronic mild HE has not been demonstrated. The aim of this work was to assess
      whether cerebral oedema contributes to cognitive and/or motor alterations in rats
      with chronic mild HE. METHODS: Motor activity and coordination and different
      types of learning and memory were assessed in rats with porta-caval shunts (PCS).
      Brain oedema was assessed by gravimetry in cerebellum and cortex and apparent
      diffusion coefficient (ADC) by magnetic resonance in 16 areas. RESULTS: Four
      weeks after surgery, PCS rats show reduced motor activity and coordination,
      impaired ability to learn a conditional discrimination task in the Y maze and
      reduced spatial memory in the Morris water maze. PCS rats did not show increased
      brain water content at 4 or 10 weeks or changes in ADC at 4 weeks. At 10 weeks,
      increased ADC in some areas is compatible with vasogenic but not cytotoxic
      oedema. CONCLUSION: Cerebral oedema is not involved in motor and cognitive
      alterations in rats (and likely in humans) with mild HE. Proper understanding of
      the mechanisms responsible for the neurological alterations in HE is necessary to
      design efficient treatments.

PMID- 23869991
TI  - Deep Ion Torrent sequencing identifies soil fungal community shifts after
      frequent prescribed fires in a southeastern US forest ecosystem.
AB  - Prescribed burning is a common management tool to control fuel loads, ground
      vegetation, and facilitate desirable game species. We evaluated soil fungal
      community responses to long-term prescribed fire treatments in a loblolly pine
      forest on the Piedmont of Georgia and utilized deep Internal Transcribed Spacer
      Region 1 (ITS1) amplicon sequencing afforded by the recent Ion Torrent Personal
      Genome Machine (PGM). These deep sequence data (19,000 + reads per sample after
      subsampling) indicate that frequent fires (3-year fire interval) shift soil
      fungus communities, whereas infrequent fires (6-year fire interval) permit system
      resetting to a state similar to that without prescribed fire. Furthermore, in
      nonmetric multidimensional scaling analyses, primarily ectomycorrhizal taxa were
      correlated with axes associated with long fire intervals, whereas soil saprobes
      tended to be correlated with the frequent fire recurrence. We conclude that (1)
      multiplexed Ion Torrent PGM analyses allow deep cost effective sequencing of
      fungal communities but may suffer from short read lengths and inconsistent
      sequence quality adjacent to the sequencing adaptor; (2) frequent prescribed
      fires elicit a shift in soil fungal communities; and (3) such shifts do not occur
      when fire intervals are longer. Our results emphasize the general responsiveness
      of these forests to management, and the importance of fire return intervals in
      meeting management objectives.

PMID- 23869992
TI  - Formin-mediated actin polymerization promotes Salmonella invasion.
AB  - Salmonella invade host cells using Type 3 secreted effectors, which modulate host
      cellular targets to promote actin rearrangements at the cell surface that drive
      bacterial uptake. The Arp2/3 complex contributes to Salmonella invasion but is
      not essential, indicating other actin regulatory factors are involved. Here, we
      show a novel role for FHOD1, a formin family member, in Salmonella invasion.
      FHOD1 and Arp2/3 occupy distinct microdomains at the invasion site and control
      distinct aspects of membrane protrusion formation. FHOD1 is phosphorylated during
      infection and this modification is required for promoting bacterial uptake by
      host cells. ROCK II, but not ROCK I, is recruited to the invasion site and is
      required for FHOD1 phosphorylation and for Salmonella invasion. Together, our
      studies revealan important phospho-dependent FHOD1 actin polymerization pathway
      in Salmonella invasion. 

PMID- 23869993
TI  - Neuroprotective effect of Danshensu derivatives as anti-ischaemia agents on SH
      SY5Y cells and rat brain.
AB  - Novel Danshensu derivatives (3-8) were designed and synthesized to improve
      bioactivity based on the strategy of 'medicinal chemical hybridization'. Our
      previous studies indicated that these compounds exhibited noticeable
      cardioprotective activities. Here, we investigate whether these novel Danshensu
      derivatives exert neuroprotective activities. An in vitro study revealed that
      these compounds could increase cell viability and reduce LDH (lactate
      dehydrogenase) leakage. Moreover, Danshensu-cysteine derivative compounds 6 and 8
      could significantly inhibit lipid peroxidation of cell membrane and regulate the
      expression of apoptosis-related protein (Bcl-2, Bax and caspase 3). An in vivo
      study demonstrated that treatment with compound 6 at 30 mg/kg markedly decreased
      the infarct volume of MCAO (middle cerebral artery occlusion) insulted rat brain.
      Furthermore, treatment with compound 6 showed the antioxidant capacity by
      increasing the activity of SOD (superoxide dismutase) and GPx (glutathione
      peroxidase) and decreasing the level of MDA (malondialdehyde) and the ROS
      (reactive oxygen species) production significantly. These results suggested that
      these novel conjugates exert significant neuroprotective effects as anti
      ischaemia agents and those with high potential merit further investigation. 

PMID- 23869994
TI  - Growth responses and ion accumulation in the halophytic legume Prosopis
      strombulifera are determined by Na2SO4 and NaCl.
AB  - Halophytes are potential gene sources for genetic manipulation of economically
      important crop species. This study addresses the physiological responses of a
      widespread halophyte, Prosopis strombulifera (Lam.) Benth to salinity. We
      hypothesised that increasing concentrations of the two major salts present in
      soils of central Argentina (Na2SO4, NaCl, or their iso-osmotic mixture) would
      produce distinct physiological responses. We used hydroponically grown P.
      strombulifera to test this hypothesis, analysing growth parameters, water
      relations, photosynthetic pigments, cations and anions. These plants showed a
      halophytic response to NaCl, but strong general inhibition of growth in response
      to iso-osmotic solutions containing Na2SO4. The explanation for the adaptive
      success of P. strombulifera in high NaCl conditions seems to be related to a
      delicate balance between Na(+) accumulation (and its use for osmotic adjustment)
      and efficient compartmentalisation in vacuoles, the ability of the whole plant to
      ensure sufficient K(+) supply by maintaining high K(+)/Na(+) discrimination, and
      maintenance of normal Ca(2+) levels in leaves. The three salt treatments had
      different effects on the accumulation of ions. Findings in bi-saline-treated
      plants were of particular interest, where most of the physiological parameters
      studied showed partial alleviation of SO4(2-)-induced toxicity by Cl(-). Thus,
      discussions on physiological responses to salinity could be further expanded in a
      way that more closely mimics natural salt environments.

PMID- 23869995
TI  - An examination of interactions among children with autism and their typically
      developing peers.
AB  - OBJECTIVE: To determine whether pre-school children with Autism Spectrum
      Disorders (ASD) interact differently with their peers with ASD compared to their
      typically developing (TD) peers, across three activities (free play, structured
      group time and semi-structured play) in an early intervention setting. METHODS:
      We completed a series of non-experimental case studies involving 13 children with
      ASD and two TD peers. RESULTS: We found trends, but no uniform differences, in
      the frequency or quality of means by which the children with ASD interacted with
      one another versus with their TD peers across the three contexts. The children
      with ASD interacted with both peer types more frequently during the semi
      structured and structured activities, than during free play. CONCLUSIONS: The
      children with ASD showed no clear bias towards one peer type over the other. Semi
      structured activities may be the best context in which to facilitate peer
      interactions involving children with ASD in early intervention settings.

PMID- 23869996
TI  - How does altering the resolution of chromosomal microarray analysis in the
      prenatal setting affect the rates of pathological and uncertain findings?
AB  - OBJECTIVE: Chromosomal Microarray Analysis (CMA) has a higher detection rate of
      pathogenic chromosome abnormalities over conventional (G-band) karyotyping. The
      optimum resolution of CMA in the prenatal setting remains debatable. Our
      objective was to determine if an increased detection rate was obtained by
      performing differing resolution of CMA on the same fetal samples and whether this
      resulted in an increase in variants of uncertain clinical significance (VOUS).
      METHODS: Sixty-two fetal cases initially underwent a 1 Mb targeted BAC microarray
      within a clinical diagnostic setting in addition to conventional karyotyping. At
      the conclusion of pregnancy, a higher resolution 60 K oligonucleotide microarray
      was performed. RESULTS: The 1 Mb BAC analysis demonstrated a detection rate of
      pathogenic copy number variations (CNVs) in 4.1% (95% CI 2.1-7.6) of cases and a
      variation of unknown significance (VOUS) rate of 0.4% (95% CI 0.07-2.2) over
      conventional G-band karyotyping. The 60 K array had an additional pathogenic
      detection rate of 4.8% (95% CI 1.6-13.3) over the BAC array but also detected an
      additional 8% (95% CI 1.3-14.8) VOUS. CONCLUSION: As the CMA platform resolution
      increases detection rates increase but are associated with an increase in VOUS
      rates. Our findings support the need for further large scale studies to inform
      the national consensus on the resolution required and on reporting of VOUS in the
      antenatal setting.

PMID- 23869997
TI  - Effects of knowledge of an endangered species on recreationists' attitudes and
      stated behaviors and the significance of management compliance for ohlone tiger
      beetle conservation.
AB  - Recreation is a leading cause of species decline on public lands, yet sometimes
      it can be used as a tool for conservation. Engagement in recreational activities,
      such as hiking and biking, in endangered species habitats may even enhance public
      support for conservation efforts. We used the case of the endangered Ohlone tiger
      beetle (Cicindela ohlone) to investigate the effect of biking and hiking on the
      beetle's behavior and the role of recreationists' knowledge of and attitudes
      toward Ohlone tiger beetle in conservation of the species. In Inclusion Area A on
      the University of California Santa Cruz (U.S.A.) campus, adult Ohlone tiger
      beetles mate and forage in areas with bare ground, particularly on recreational
      trails; however, recreation disrupts these activities. We tested the effect of
      recreation on Ohlone tiger beetles by observing beetle behavior on trails as
      people walked and road bikes at slow and fast speed and on trails with no
      recreation. We also surveyed recreationists to investigate how their knowledge of
      the beetle affected their attitudes toward conservation of the beetle and stated
      compliance with regulations aimed at beetle conservation. Fast cycling caused the
      beetles to fly off the trail more often and to fly farther than slow cycling or
      hiking. Slow cycling and hiking did not differ in their effect on the number of
      times and distance the beetles flew off the trail. Recreationists' knowledge of
      the beetle led to increased stated compliance with regulations, and this stated
      compliance is likely to have tangible conservation outcomes for the beetle. Our
      results suggest management and education can mitigate the negative effect of
      recreation and promote conservation of endangered species. Efectos del
      Conocimiento de una Especie en Peligro sobre las Actitudes y Comportamientos
      Declarados de los Recreacionistas y el Significado del Manejo de la Conformidad
      para la Conservacion del Escarabajo Tigre de Ohlone. 

PMID- 23869998
TI  - Mesenchymal stromal cells promote bowel regeneration after intestinal
      transplantation: myth to mucosa.

PMID- 23869999
TI  - Effect of medication reconciliation on unintentional medication discrepancies in
      acute hospital admissions of elderly adults: a multicenter study.
AB  - OBJECTIVES: To investigate the effect of pharmacy-based medication reconciliation
      on the frequency of unintentional medication discrepancies in acutely admitted
      individuals aged 65 and older. DESIGN: Multicenter intervention study with pre
      post design. SETTING: Twelve Dutch hospitals. PARTICIPANTS: One thousand five
      hundred forty-three individuals aged 65 and older with an acute hospital
      admission through the emergency department. MEASUREMENTS: The intervention
      consisted of the Best Possible Medication History (BPMH), based on combining
      information from the community pharmacy record, the information provided by a
      structured interview with participants about their medication use, and medication
      containers. In nine hospitals, pharmacy technicians obtained the BPMH, and in
      three hospitals, a mixed model was used (physicians or pharmacy technicians
      obtained the BPMH). Primary outcome measure was the proportion of participants
      with one or more unintentional medication discrepancies. The primary outcome
      measure was stratified according to type of intervention (pharmacy based vs mixed
      model). RESULTS: The proportion of participants with one or more unintentional
      medication discrepancies was reduced from 62% to 32% [odds ratio (OR) = 0.29, 95%
      confidence interval (CI) = 0.23-0.37]. These results remained statistically
      significant after adjustment for type of department and hospital (OR = 0.20, 95%
      CI = 0.15-0.26), and this effect remained stable for 6 months. Stratified
      analysis showed that no effect from the intervention was evident in the three
      hospitals with a mixed-model intervention, in contrast to the hospitals with a
      pharmacy-based intervention. The medication discrepancy types "omission" and
      "dosage or strength" occurred most frequently and were the main types that the
      intervention influenced. CONCLUSION: Pharmacy-based medication reconciliation
      leads to a substantial reduction in medication discrepancies in acutely admitted
      elderly adults.

PMID- 23870002
TI  - An analysis of contingency statements in a DRO procedure: A case report.
AB  - OBJECTIVE: To examine latency to criterion for reduction of challenging behaviour
      with and without stating a contingency statement immediately prior to a DRO
      procedure. METHOD: An ABAC design in which A was baseline, B was used to evaluate
      the efficacy of a DRO procedure, and C was used to evaluate the efficacy of a DRO
      procedure with a contingency statement. RESULTS: The DRO with the contingency
      statement intervention was associated with a shorter latency to behaviour change
      than the DRO procedure without the contingency statement. DISCUSSION: These
      preliminary findings from this case study highlight the importance of examining
      the efficiency of behaviour change procedures. Directions for future research are
      provided.

PMID- 23870000
TI  - ALS Untangled No. 21: Fecal transplants.

PMID- 23870001
TI  - The redox-associated adaptive response of brain to physical exercise.
AB  - Reactive oxygen species (ROS) are continuously generated during metabolism. ROS
      are involved in redox signaling, but in significant concentrations they can
      greatly elevate oxidative damage leading to neurodegeneration. Because of the
      enhanced sensitivity of brain to ROS, it is especially important to maintain a
      normal redox state in brain and spinal cord cell types. The complex effects of
      exercise benefit brain function, including functional enhancement as well as its
      preventive and therapeutic roles. Exercise can induce neurogenesis via
      neurotrophic factors, increase capillarization, decrease oxidative damage, and
      enhance repair of oxidative damage. Exercise is also effective in attenuating age
      associated loss in brain function, which suggests that physical activity-related
      complex metabolic and redox changes are important for a healthy neural system.

PMID- 23870003
TI  - Detection of New Delhi metallo-beta-lactamase and extended-spectrum beta
      lactamase genes in Escherichia coli isolated from mastitic milk samples.
AB  - In this study, eight Escherichia coli isolates were obtained from milk samples of
      dairy cattle suffering from clinical/subclinical mastitis. Isolates were
      characterized for antimicrobial resistance traits and virulence genes. Results
      revealed that one isolate was harbouring New Delhi metallo-beta-lactamase gene
      (blaNDM ). Cloning and sequencing of the PCR amplicon confirmed the identity of
      the gene (GenBank accession no. KC769583) having 100% homology with blaNDM-5
      (GenBank accession no. JN104597.1), and this isolate was susceptible to colistin,
      chloramphenicol and tetracycline only. Moreover, another isolate carried extended
      spectrum beta-lactamase (ESBL) gene - blaCTX-M , and all isolates possessed
      blaTEM gene. Of the eight isolates, only one isolate was positive for shiga toxin
      gene (stx2), and none were harbouring stx1 gene. Occurrence of New Delhi metallo
      beta-lactamase (blaNDM ) in one E. coli isolate and ESBL genes in other isolates
      poses a potential threat to human health following possible entry and spread
      through food chain. 

PMID- 23870004
TI  - Parents' experiences with neonatal home care following initial care in the
      neonatal intensive care unit: a phenomenological hermeneutical interview study.
AB  - AIM: A descriptive study of parents' experiences with neonatal home care
      following initial care in the neonatal intensive care unit. BACKGROUND: As
      survival rates improve among premature and critically ill infants with an
      increased risk of morbidity, parents' responsibilities for neonatal care grow in
      scope and degree under the banner of family-centred care. Concurrent with medical
      advances, new questions arise about the role of parents and the experience of
      being provided neonatal care at home. DESIGN: An interview study with a
      phenomenological hermeneutic approach. METHODS: Parents from a Swedish neonatal
      (n = 22) home care setting were extensively interviewed within one year of
      discharge. Data were collected during 2011-2012. FINDINGS: The main theme of the
      findings is that parents experience neonatal home care as an inner emotional
      journey, from having a child to being a parent. This finding derives from three
      themes: the parents' experience of leaving the hospital milieu in favour of
      establishing independent parenthood, maturing as a parent and processing
      experiences during the period of neonatal intensive care. CONCLUSIONS: This study
      suggests that neonatal home care is experienced as a care structure adjusted to
      incorporate parents' needs following discharge from a neonatal intensive care
      unit. Neonatal home care appears to bridge the gap between hospital and home,
      supporting the family's adaptation to life in the home setting. Parents become
      empowered to be primary caregivers, having nurse consultants serving the needs of
      the whole family. Neonatal home care may therefore be understood as the
      implementation of family-centred care during the transition from NICU to home.

PMID- 23870005
TI  - Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis: a comparison
      with bacteremia caused by Enterobacteriaceae.
AB  - BACKGROUND: This study was performed to detect risk factors for Pseudomonas
      aeruginosa bacteremia in patients with liver cirrhosis. METHODS: A retrospective
      case-control study was designed to identify risk factors for P. aeruginosa
      bacteremia in cirrhotic patients. The cases were cirrhotic patients with P.
      aeruginosa bacteremia and the controls were cirrhotic patients with
      Enterobacteriaceae bacteremia. RESULTS: Sixty-one cases and the same number of
      controls were enrolled. In a multivariate analysis, younger age {adjusted odds
      ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial
      acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary
      disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to
      immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were
      associated with P. aeruginosa bacteremia. In the case group the frequency of
      appropriate initial antibiotic regimens was considerably lower than in the
      control group: 29.5% vs. 65.6% (P <0.01). However, thirty day mortality did not
      differ significantly between cases and controls (19.7% vs. 24.6%). CONCLUSIONS:
      Nosocomial acquisition, preexisting biliary disease, and recent use of
      immunosuppressive agents are strong predictive factors for P. aeruginosa
      bacteremia in cirrhotic patients.

PMID- 23870006
TI  - Delayed healing at transurethral resection of bladder tumour sites after
      immediate postoperative mitomycin C instillation.
AB  - The most common reactions to mitomycin C are dysuria and drug-related palmar and
      genital desquamation. This report describes two cases of delayed healing of the
      mucosa at resection sites after transurethral resection of bladder tumours, most
      likely due to immediate postoperative mitomycin C instillation of the bladder.

PMID- 23870008
TI  - Retraction: Heterologous expression, purification and characterization of
      nitrilase from Aspergillus niger K10.

PMID- 23870009
TI  - The use of technology to promote physical activity in Type 2 diabetes management:
      a systematic review.
AB  - INTRODUCTION: With increasing evidence available on the importance of physical
      activity in the management of Type 2 diabetes, there has been an increase in
      technology-based interventions. This review provides a systematic and descriptive
      assessment of the effectiveness of technology to promote physical activity in
      people with Type 2 diabetes. For this review, technology included mobile phones
      and text messages, websites, CD-ROMs and computer-learning-based technology, and
      excluded telephone calls. METHODS: A systematic literature search was conducted
      to retrieve articles from January 2001 to March 2013 using the following
      databases: the Cochrane Library, EMBASE, MEDLINE, PsycINFO and PubMed. Articles
      had to describe an intervention that used technology to promote physical activity
      in people with Type 2 diabetes. A methodological quality assessment of the
      studies was conducted and data synthesis was performed. RESULTS: In total, 15
      articles were eligible for review: web-based (9), mobile phone (3), CD-ROM (2)
      and computer based (1). All studies found an increase in physical activity but
      only nine were significant. The use of a personal coach, logbooks and
      reinforcement strategies such as phone calls and email counselling were found to
      be effective components for behaviour change. No studies were ranked as low in
      terms of methodological quality. CONCLUSIONS: Technology-based interventions to
      promote physical activity are effective; using further methods to promote
      participant adherence is associated with greater benefit. Further research should
      look into strategies to enhance adherence and sustainability in order to increase
      the effectiveness of technology-based physical activity intervention in diabetes
      care.

PMID- 23870010
TI  - Adult root structure of Mediterranean shrubs: relationship with post-fire
      regenerative syndrome.
AB  - Life-history attributes can impose differences on root system structures and
      properties related to nutrient and water uptake. Here, we assess whether plants
      with different post-fire regenerative strategies (resprouters, seeders and seeder
      resprouters) differ in the topological and morphological properties of their root
      systems (external path, altitude, magnitude, topological index, specific root
      length, root length, root-to-shoot biomass ratio, length of the main axis of the
      root system and link length). To achieve these objectives, we sampled individuals
      from eight woody species in a shrubland located in the western Mediterranean
      Basin. We sampled the adult root systems using manual field excavation with the
      aid of an air compressor. The results indicate that resprouters have a higher
      root-to-shoot ratio, confirming their higher ability to store water, starch and
      nutrients and to invest in the belowground biomass. Moreover, this pattern would
      allow them to explore deeper parts of the soil layers. Seeder species would
      benefit from a higher specific root length, pointing to increased relative root
      growth and water uptake rates. This study confirms that seeders and resprouters
      may differ in nutrient and water uptake ability according to the characteristics
      of their root system. Species that can both resprout and establish seedlings
      after fire had different patterns of root system structure; in particular,
      root:shoot ratio was more similar to resprouters and specific root length was
      closer to seeders, supporting the distinct functional performance of this type of
      species. 

PMID- 23870011
TI  - Effects of gestational age on physical findings of immaturity, body weight, and
      survival in neonatal alpacas (2002-2010).
AB  - BACKGROUND: Gestational duration is highly variable in camelids (reference range
      330-360 days), and a definition for prematurity has not been established.
      Anecdotally, it is suggested that crias born outside of this have increased
      incidence of physical findings of immaturity (tendon laxity, floppy ears, and
      unerupted teeth) and need increased intensive support in the neonatal period.
      OBJECTIVES: Low gestational age (<330 days) is associated with physical findings
      of immaturity, low birth weight, more intensive and expensive care, but not
      decreased short-term survival. ANIMALS: A total of 130 alpacas presented to the
      University of Wisconsin. METHODS: Retrospective study of all neonatal crias <1
      month of age. RESULTS: Of 130 neonatal alpacas presented, 86 (66%) had
      gestational age recorded (range 312-393 days). There were 16 (18.6%) crias with
      gestational age below 330 days. Crias born before 330 days were lighter at birth
      (mean 6.4 kg, SD 1.3 kg) than those born after 330 days (mean 7.4 kg, SD 1.7 kg,
      P = .002). Clinically immature crias had lower birth weights (mean 6.5 kg, SD 1.5
      kg) than physically mature crias (mean 8.8 kg, SD 3.2 kg, P = .05). Survival
      rates were similar in all groups (premature 77%, mature 88%, P = .12). However,
      treatment costs were higher in crias born prior to 330 days with physical
      findings at birth consistent with immaturity compared with gestationally mature
      crias and those born prior to 330 days but with a physically mature appearance.
      CONCLUSIONS: Crias born before 330 days and those with physical findings of
      immaturity have a good prognosis, but require more intensive care, resulting in
      higher treatment costs.

PMID- 23870012
TI  - Repeat liver resection after a hepatic or extended hepatic trisectionectomy for
      colorectal liver metastasis.
AB  - OBJECTIVE: A right and left hepatic trisectionectomy and an extended
      trisectionectomy are the largest liver resections performed for malignancy. This
      report analyses a series of 23 patients who had at least one repeat resection
      after a hepatic trisectionectomy for colorectal liver metastasis (CRLM). METHODS:
      A retrospective analysis of a single-centre prospective liver resection database
      from May 1996 to April 2009 was used for patient identification. Full notes,
      radiology and patient reviews were analysed for a variety of factors with respect
      to survival. RESULTS: Twenty-three patients underwent up to 3 repeat hepatic
      resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients
      the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year
      survival rates after a repeat resection were 100%, 46% and 32%, respectively. No
      factors predictive for survival were identified. CONCLUSION: A repeat resection
      after a hepatic trisectionectomy for CRLM can offer extended survival and should
      be considered where appropriate.

PMID- 23870013
TI  - Developmental profile of speech-language and communicative functions in an
      individual with the preserved speech variant of Rett syndrome.
AB  - OBJECTIVE: We assessed various aspects of speech-language and communicative
      functions of an individual with the preserved speech variant of Rett syndrome
      (RTT) to describe her developmental profile over a period of 11 years. METHODS:
      For this study, we incorporated the following data resources and methods to
      assess speech-language and communicative functions during pre-, peri- and post
      regressional development: retrospective video analyses, medical history data,
      parental checklists and diaries, standardized tests on vocabulary and grammar,
      spontaneous speech samples and picture stories to elicit narrative competences.
      RESULTS: Despite achieving speech-language milestones, atypical behaviours were
      present at all times. We observed a unique developmental speech-language
      trajectory (including the RTT typical regression) affecting all linguistic and
      socio-communicative sub-domains in the receptive as well as the expressive
      modality. CONCLUSION: Future research should take into consideration a
      potentially considerable discordance between formal and functional language use
      by interpreting communicative acts on a more cautionary note.

PMID- 23870014
TI  - Synthesis and polymerization of bicyclic ketals: a practical route to high
      molecular weight polyketals.
AB  - Polyketals are an important class of materials for drug delivery to sensitive
      tissues as they degrade in vivo to nonacidic species. We report the synthesis of
      high-molecular weight cyclic polyketals by the cationic ring-opening
      polymerization of bicyclic ketal monomers, which were prepared by the metal
      catalyzed rearrangement of epoxy ketones. Three different cyclic polyketals with
      high molecular weights were synthesized using this protocol. 

PMID- 23870015
TI  - Protargol synthesis: an in-house protocol.
AB  - The protargol staining method has proved to be indispensable for revealing the
      cellular structures of a variety of protozoa, especially the flagellates and
      ciliates. Protargol provides permanent stains of a variety of cellular
      structures: nuclei, extrusomes, basal bodies, and microfilamentous constituents
      of cells. Together with the older silver nitrate methods, protargol impregnations
      have provided the basis for the detailed descriptions of nearly all ciliates to
      date. The performance of commercially available preparations has varied widely.
      Recently, suppliers have stopped stocking the effective forms of protargol
      resulting in a worldwide shortage. Thus, it has become necessary for
      protistologists to explore on-site synthesis of this critically important agent.
      An optimum protocol for synthesis of protargol should be rapid, relatively
      inexpensive, simple enough to be done by non-chemists, and achievable without
      specialized equipment. In this article, the authors briefly review the
      interesting history of protargol and describe a protocol, based on the early
      studies of neuroanatomists, that yields a protargol producing impregnations of
      ciliates comparable to those obtained with previously available commercial
      preparations. 

PMID- 23870016
TI  - Ladislau Steiner, 1920-2013.
AB  - The authors commemorate the life and career of Dr. Ladislau Steiner, one of the
      world's most highly regarded neurosurgeons, from Stockholm and Charlottesville,
      Virginia, who has died at age 92. They review the events of Dr. Steiner's early
      life, including his early training in his native Romania, his escape with his
      family from East Berlin, and his postgraduate training in neurosurgery at the
      Karolinska Institute in Stockholm. Dr. Steiner's work in the development of
      microsurgery and his collaboration with Lars Leksell in the development of Gamma
      Knife radiosurgery are described. After his retirement from Karolinska, Dr.
      Steiner had a second career as head of the Lars Leksell Gamma Knife Center at the
      University of Virginia in Charlottesville. The authors recall their own long
      association with Dr. Steiner and celebrate his contributions to the field of
      neurosurgery. 

PMID- 23870017
TI  - Proximal subcutaneous migration of the distal end of a ventriculoperitoneal shunt
      presenting with recurrent cerebrospinal fluid galactorrhea.
AB  - The authors report an unusual case of recurrent proximal migration of the distal
      end of a ventriculoperitoneal shunt catheter presenting as CSF galactorrhea. The
      authors review the pertinent literature and discuss the possible causes as well
      as techniques to prevent a similar occurrence. 

PMID- 23870018
TI  - Motor function after stereotactic radiosurgery for brain metastases in the region
      of the motor cortex.
AB  - OBJECT: The authors sought to better define the clinical response of patients who
      underwent stereotactic radiosurgery (SRS) for brain metastases located in the
      region of the motor cortex. METHODS: A retrospective analysis was performed in
      2026 patients with brain metastasis who underwent SRS with the Gamma Knife
      between 2002 and 2012, and multiple factors that affect motor function before and
      after SRS were evaluated. Ninety-four patients with tumors >= 1.5 cm in diameter
      located in or adjacent to the motor strip were identified, including 2 patients
      with bilateral motor strip metastases. RESULTS: Motor function improved after SRS
      in 30 (31%) of 96 cases, remained stable in 48 (50%), and worsened over time in
      18 (19%) instances. Forty-seven patients had no motor weakness prior to
      radiosurgery; 10 (22%) developed new Grade 3/5-4/5 weakness. Thirty (68%) of 44
      patients with >= 3/5 pre-SRS weakness improved, 6 (14%) remained stable, and 8
      (18%) worsened. Three of 5 patients with < 3/5 pre-SRS motor function improved.
      Motor deficits prior to SRS did not correlate with a worse outcome; however,
      worse outcomes were associated with larger tumor volumes. The median tumor volume
      in patients whose function improved or remained stable was 5.3 cm(3), but it was
      9.2 cm(3) in patients who worsened (p < 0.05). Tumor volumes > 9 cm(3) were
      associated with a higher risk of worsening motor function. Adverse radiation
      effects occurred in 5 patients. CONCLUSIONS: Most intact patients with brain
      metastases in or adjacent to motor cortex maintained neurological function after
      SRS, and most patients with symptomatic motor weakness remained stable or
      improved. Larger tumor volumes were associated with less satisfactory outcomes.

PMID- 23870019
TI  - Fluid-fluid level in cystic vestibular schwannoma: a predictor of peritumoral
      adhesion.
AB  - OBJECT: The aim of this study was to evaluate the clinical results and surgical
      outcomes of cystic vestibular schwannomas (VSs) with fluid-fluid levels. METHODS:
      Forty-five patients with cystic VSs and 86 with solid VSs were enrolled in the
      study. The patients in the cystic VSs were further divided into those with and
      without fluid-fluid levels. The clinical and neuroimaging features,
      intraoperative findings, and surgical outcomes of the 3 groups were
      retrospectively compared. RESULTS: Peritumoral adhesion was significantly greater
      in the fluid-level group (70.8%) than in the nonfluid-level group (28.6%) and the
      solid group (25.6%; p < 0.0001). Complete removal of the VS occurred
      significantly less in the fluid-level group (45.8%, 11/24) than in the nonfluid
      level group (76.2%, 16/21) and the solid group (75.6%, 65/86; p = 0.015).
      Postoperative facial nerve function in the fluid-level group was less favorable
      than in the other 2 groups; good/satisfactory facial nerve function 1 year after
      surgery was noted in 50.0% cases in the fluid-level group compared with 83.3%
      cases in the nonfluid-level group (p = 0.038). CONCLUSIONS: Cystic VSs with fluid
      fluid levels more frequently adhered to surrounding neurovascular structures and
      had a less favorable surgical outcome. A possible mechanism of peritumoral
      adhesion is intratumoral hemorrhage and consequent inflammatory reactions that
      lead to destruction of the tumor-nerve barrier. These findings may be useful in
      predicting surgical outcome and planning surgical strategy preoperatively.

PMID- 23870020
TI  - Vestibular schwannoma surgery in the elderly: a matched cohort study.
AB  - OBJECT: The authors' objective was 2-fold: 1) to compare outcomes of
      microsurgical resection for vestibular schwannoma (VS) between patients aged 70
      years or older and patients younger than 70 years and 2) to test the hypothesis
      that symptomatic tumors in elderly patients represent a more aggressive variant
      of VS than those in younger adults, resulting in increased morbidity and a higher
      rate of recurrence after subtotal resection (STR). METHODS: A retrospective
      matched cohort study was conducted. Patients aged 70 years or older who had
      undergone microsurgical resection of VS were matched to adult patients younger
      than 70 years; the matching was performed on the basis of surgical approach,
      completeness of resection, and tumor size. Associations between clinical,
      radiographic, and surgical data and postoperative outcome were analyzed using
      conditional logistic regression. RESULTS: Twenty patients aged 70 years or older
      (mean age +/- SD 75.9 +/- 5.3, range 70-86 years) were identified and matched to
      a cohort of younger adult patients (mean age +/- SD 55.7 +/- 13.8, range 25-69
      years). The mean tumor size in both groups was approximately 3 cm. Overall, the
      elderly patients had a poorer preoperative American Society of Anesthesiology
      physical status score (p = 0.038), were more likely to report imbalance (OR 9.61,
      p = 0.016), and more commonly exhibited compromised balance and coordination (OR
      9.61, p = 0.016) than patients in the younger cohort. There were no differences
      between the 2 cohorts in perioperative complications (p = 0.26) or facial nerve
      function (p > 0.5) at any time. The elderly patients were 13 times more likely to
      have long-term postoperative imbalance (OR 13.00, p = 0.013) than the younger
      patients. Overall, 9 tumors recurred among 32 patients undergoing STR; 6 of these
      patients underwent additional interventions (stereotactic radiosurgery in 5
      patients and microsurgery in 1) and showed no evidence of tumor progression at
      the last follow-up. The median growth rate of the recurrent tumor in the 6
      elderly patients was 4.8 mm/year (range 2.1-14.9 mm/year) and, in the 3 control
      patients, 2.2 mm/year (range 1.9-4.0 mm/year). Overall, the mortality data showed
      a trend toward statistical significance (p = 0.068) with a higher risk of death
      in the elderly. CONCLUSIONS: As the number of elderly patients with VS increases,
      microsurgical resection will remain an important management option for these
      patients. Despite a poorer preoperative physical status in elderly patients,
      their morbidity profiles are similar to those in adult patients younger than 70
      years. However, elderly patients may require longer convalescence due to
      prolonged postoperative imbalance. Not surprisingly, overall diminished
      functional reserve and advanced comorbidities may increase the mortality risk
      associated with surgical intervention in the elderly patients. Finally, there was
      a high risk of further tumor growth following STR in the elderly patients (6
      [37.5%] of 16), underscoring the need for close postoperative radiological
      surveillance and consideration of early stereotactic radiosurgery for the tumor
      remnant following the STR.

PMID- 23870021
TI  - Definitive treatment of vein of Galen aneurysmal malformation with stereotactic
      radiosurgery.
AB  - Vein of Galen aneurysmal malformations (VGAMs) are uncommon congenital
      malformations arising from fistulous communication with the median vein of the
      prosencephalon, a primitive precursor of midline cerebral venous structures.
      Angiographic embolization is the primary modality for treatment given
      historically poor microsurgical outcomes. Only a few reports of treatment by
      Gamma Knife radiosurgery (GKRS) exist in the literature, and the results are
      variable. The authors present 2 cases of VGAM in which GKRS provided definitive
      treatment with good outcome: one case involving antenatal presentation of a high
      output, mural-type VGAM with complex clinical course refractory to multiple
      embolic procedures, and the other a choroidal-type VGAM presenting with
      hemorrhage in an adult and without a feasible embolic approach. With discussion
      of these cases and review of the literature, the authors advocate inclusion of
      GKRS as a therapeutic option for treatment of these complex lesions. 

PMID- 23870022
TI  - What is talked about? Community living staff experiences of talking with older
      people with intellectual disability about dying and death.
AB  - BACKGROUND: The aim of this study was to explore what community living staff
      talked about and did with people with intellectual disability (ID) to assist them
      to understand dying and death. METHOD: Guided by grounded theory methodology,
      focus groups and one-to-one interviews were conducted with 22 staff who had
      talked about any topic relating to dying and death with their clients. RESULTS:
      There was little evidence that staff talked with, or did things with clients to
      assist understanding of the end of life, both prior to and after a death. Prior
      to death staff assisted clients in a limited way to understand about determining
      wishes in preparation for death, and what dying looks like by observance of its
      passage. Following a death staff offered limited assistance to clients to
      understand the immutability of death, and how the dead can be honoured with
      ritual, and remembered. CONCLUSIONS: The findings have implications for why
      people with ID have only partial understanding of the end of life, the staff
      skills required to support clients' understanding, and when conversations about
      the end of life should occur.

PMID- 23870023
TI  - Predictors of in-hospital mortality after acute variceal bleeding in patients
      with hepatocellular carcinoma and concurrent main portal vein thrombosis.
AB  - BACKGROUND AND AIM: Risk factors for acute variceal bleeding in patients with
      hepatocellular carcinoma (HCC) and concurrent main portal vein thrombosis (PVT)
      remain unclear. We aimed to determine risk factors of in-hospital mortality after
      acute variceal bleeding for HCC patients with concurrent main PVT. METHODS: We
      conducted a retrospective analysis of 102 HCC patients (83% men and 17% women)
      with concurrent main PVT and acute variceal bleeding. All patients received
      emergent endoscopy to define the bleeding source. Multivariable Cox proportional
      hazard regression analysis consisting of clinical, laboratory, and endoscopic
      parameters was performed to identify predictive factors for intrahospital
      mortality. RESULTS: Twenty-eight (27.5%) patients died within admission. The
      median survival of all patients was 56 days. Multivariable Cox proportional
      hazard regression analyses revealed Child-Pugh score (adjusted hazard ratio
      [aHR]: 1.29 for each point; 95% confidence interval [CI]: 1.11-1.50), active
      bleeding on index endoscopy (aHR: 7.50; 95% CI: 3.05-18.4), esophageal varices as
      the bleeder (compared with gastric varices, aHR: 14.3; 95% CI: 3.12-66.1),
      failure to control bleeding (aHR: 38.0; 95% CI: 7.44-194), and serum creatinine
      (aHR: 1.28 for each increase of 1 mg/dL; 95% CI: 1.09-1.50) independently
      predicted in-hospital mortality. CONCLUSIONS: Hepatic reserve, active bleeding on
      index endoscopy, failure to control bleeding, esophageal varices as the bleeder
      when compared with gastric varices, and renal function were independent
      predictive factors for in-hospital mortality in HCC patients with acute variceal
      bleeding and concurrent main PVT.

PMID- 23870024
TI  - Importance of microbial soil organic matter processing in dissolved organic
      carbon production.
AB  - Soil dissolved organic carbon (DOC) sources and its seasonal dynamics are poorly
      known. We aimed to determine the contribution of plant and soil organic matter
      (SOM) to size classes of DOC in a field experiment with C3 to C4 vegetation
      change on two soil types through different seasons. Stable isotope ratios of DOC
      size classes were measured using size exclusion chromatography (SEC) coupled
      online to liquid chromatography-isotope ratio mass spectrometry (LC-IRMS). SEC
      resolved DOC into three size classes: very high molecular weight/vHMW (> 10 kDa),
      high molecular weight/HMW (0.4-10 kDa), and low molecular weight/LMW (< 0.4 kDa).
      HMW DOC was most abundant in all seasons, soil types, and depths. In contrast,
      vHMW DOC was only seen postsnowmelt in upper 20 cm and was mainly (87 +/- 9%)
      plant-derived. Through all seasons, HMW and LMW DOC had less than 30% recent
      plant contribution. Similar size range and source of DOC size classes and soil
      chloroform fumigation extracts suggest microbial origin of DOC. Thus, microbial
      SOM recycling is an important process in DOC production. We suggest that DOC
      molecules get partitioned manifold between soil solution and the mineral matrix
      (chromatography), thereby getting constantly decomposed, altered, or produced
      anew by soil microorganisms (reactive transport). 

PMID- 23870025
TI  - The effect of free air carbon dioxide enrichment and nitrogen fertilisation on
      the chemical composition and nutritional value of wheat and barley grain.
AB  - A rising atmospheric CO2 concentration might influence the nutrient composition
      of feedstuffs and consequently the nutritional value for livestock. The present
      study investigates the effects of atmospheric CO2 enrichment on the chemical
      composition and nutritional value of winter wheat cv. "Batis" and winter barley
      cv. "Theresa". Both cereals were grown at two different atmospheric CO2
      concentrations (ambient CO2 [AMBI]: 380 ppm and enriched CO2 [free air carbon
      dioxide enrichment, FACE]: 550 ppm) for two growing seasons. The influence of two
      different nitrogen (N) fertilisation levels (adequate N supply [N100] and nearly
      50% of adequate N supply [N50]) were studied as well. A significant effect was
      observed for the crude protein content, which declined at FACE condition in a
      range of 8-16 g kg(-1) in wheat and of 10-20 g kg(-1) in barley. A reduced N
      fertilisation level resulted in a strong reduction of crude protein concentration
      in both cereal species. In wheat, a decrease in N supply significantly enhanced
      the concentration of starch and crude fibre. In barley, only the concentration of
      fructose increased under FACE condition and reduced N fertilisation. The FACE did
      not have major effects on the concentrations of minerals, while the influence of
      N fertilisation was different for both cereals. Whereas no effects could be
      observed for barley, a reduced N supply caused a significant reduction in
      concentrations of zinc, manganese and iron in wheat. Furthermore, an undirected
      effect of atmospheric CO2 and N fertilisation levels were found for the amino
      acid concentrations. Based on these results, future scenarios of climate change
      would have an impact on the nutritional value of cereal grains. 

PMID- 23870026
TI  - Aortic calcifications and arterial stiffness as predictors of cardiovascular
      events in incident renal transplant recipients.
AB  - Renal transplant recipients have an increased risk of cardiovascular (CV)
      disease. Arterial stiffness (AS) and aortic calcifications (ACs) are well-known
      CV risk factors in patients with chronic kidney disease. We aimed to determine
      the prognostic value of AS and AC in incident renal transplant recipients (RTRs).
      We conducted a prospective study in 253 single RTR. AC were scored by means of
      lumbar X-ray. Carotid-femoral pulse wave velocity (PWV) was assessed in a
      subgroup of 115 patients. AC were present in 61% of patients. After a mean follow
      up of 36 months, 32 CV events occurred in the overall group and 13 events in the
      PWV subgroup. When we accounted for age, gender, and CV history, AC score (HR,
      hazard ratio 1.09 per 1 unit increase; 95% CI 1.02-1.17) and PWV (HR 1.45 per 1
      m/s; 95% CI 1.16-1.8) remained an independent predictor of CV events in Cox
      regression analyses. Using receiver operating characteristics, the area under the
      curve for predicting CV events amounted to 0.80 and 0.72 for sum AC and PWV,
      respectively. Both AS and AC are strong predictors of future CV events in an
      incident RTR population. These vascular assessments are readily available and
      easy to perform, making them ideal tools for further risk stratification.
      (ClinicalTrials.gov number: NCT00547040). 

PMID- 23870028
TI  - Low chlamydia testing uptake among young pregnant women in Australia highlights
      the need for national leadership in this area.

PMID- 23870027
TI  - Relaxin decreases the severity of established hepatic fibrosis in mice.
AB  - BACKGROUND & AIMS: Hepatic fibrosis is characterized by excess collagen
      deposition, decreased extracellular matrix degradation and activation of the
      hepatic stellate cells. The hormone relaxin has shown promise in the treatment of
      fibrosis in a number of tissues, but the effect of relaxin on established hepatic
      fibrosis is unknown. The aim of this study was to determine the effect of relaxin
      on an in vivo model after establishing hepatic fibrosis METHODS: Male mice were
      made fibrotic by carbon tetrachloride treatment for 4 weeks, followed by
      treatment with two doses of relaxin (25 or 75 MUg/kg/day) or vehicle for 4 weeks,
      with continued administration of carbon tetrachloride. RESULTS: Relaxin
      significantly decreased total hepatic collagen and smooth muscle actin content at
      both doses, and suppressed collagen I expression at the higher dose. Relaxin
      increased the expression of the matrix metalloproteinases MMP13 and MMP3,
      decreased the expression of MMP2 and tissue inhibitor of metalloproteinase 2
      (TIMP2) and increased the overall level of collagen-degrading activity. Relaxin
      decreased TGFbeta-induced Smad2 nuclear localization in mouse hepatic stellate
      cells. CONCLUSIONS: The results suggest that relaxin reduced collagen deposition
      and HSC activation in established hepatic fibrosis despite the presence of
      continued hepatic insult. This reduced fibrosis was associated with increased
      expression of the fibrillar collagen-degrading enzyme MMP13, decreased expression
      of TIMP2, and enhanced collagen-degrading activity, and impaired TGFbeta
      signalling, consistent with relaxin's effects on activated fibroblastic cells.
      The results suggest that relaxin may be an effective treatment for the treatment
      of established hepatic fibrosis.

PMID- 23870029
TI  - Chlamydia screening in pregnancy in Australia: integration of national guidelines
      into clinical practice and policy.
AB  - BACKGROUND: Chlamydia trachomatis is the most common reportable infection in
      Australia. Since 2006, the Royal Australian and New Zealand College of
      Obstetricians and Gynaecologists (RANZCOG) have recommended chlamydia screening
      in pregnant women aged <25 years. AIMS: To assess clinical uptake and policy
      integration of the 2006 RANZCOG recommendation on chlamydia testing in pregnant
      women aged <25 years. METHODS: A mixed method approach was used involving a
      literature review, a survey of obstetricians and gynaecologists, and survey of
      hospital managers from April 2010 to May 2010. RESULTS: Of the 1644 participating
      RANZCOG Fellows, Trainees, and Diplomates, 21.2% reported universal screening for
      pregnant women <25 years (25% of primary care clinicians, 23% of those working in
      the public hospital sector, 16% of those working in both public and private
      hospitals, and 13% of those in private hospitals or private practice). There was
      a strong association between members who agreed with the guideline and offering
      universal screening to pregnant women aged <25 years (adjusted odds ratio = 17.1,
      95% CI: 6.0-49.2, P < 0.01). Of the 143 participating hospital managers who
      completed the hospital policy questionnaire; 20% reported that their hospital had
      a formal screening guideline. There were two national and four state/local policy
      documents recommending chlamydia screening in pregnancy. CONCLUSIONS: This study
      shows low uptake of chlamydia screening of young pregnant women by RANZCOG
      Fellows, Trainees, and Diplomates involved in antenatal care and highlights the
      need for national clinical leadership regarding screening for chlamydia among
      pregnant women aged <25 years.

PMID- 23870030
TI  - Value of diagnostic procedures in rectovaginal endometriosis.
AB  - OBJECTIVE: Rectovaginal endometriosis has the potential to infiltrate into the
      rectal wall. The recognition of infiltration prior to surgery is of utmost
      importance since only infiltrative disease should be treated by partial or
      complete rectal resection. This study compares different imaging procedures in
      rectovaginal endometriosis cases in an everyday clinical setting. METHODS:
      Seventy nine consecutive women diagnosed with rectovaginal endometriosis were
      included in this prospective study. Preoperatively, all women had a rectovaginal
      gynaecological examination and transvaginal sonography. Furthermore, MRI or
      rectal endosonography imaging procedures together with a rectosigmoidoscopy and
      estimation of a serum Ca125 were undertaken. Sensitivity and specificity of all
      diagnostic tools were compared with the intraoperative findings. RESULTS: The
      procedure with the highest accuracy was bimanual rectovaginal gynaecological
      examination (sensitivity: 0.92/specificity: 0.32). Rectal endosonography obtained
      a sensitivity of 0.44 and a specificity of 0.77. All other diagnostic procedures
      such as Ca125 (sensitivity: 0.42/specificity: 0.81), MRI (sensitivity:
      0.41/specificity: 0.83), transvaginal sonography (sensitivity: 0.2/ specificity:
      0.79) and rectosigmoidoscopy (sensitivity: 0.03/specificity: 0.92) were only of
      limited value. CONCLUSION: The diagnostic method with the highest sensitivity to
      detect bowel infiltration in an everyday clinical setting is the gynaecological
      examination. It is followed by rectal endosonography. However, none of the
      currently available preoperative diagnostic tools can predict infiltrative growth
      of rectovaginal endometriosis with any certainty. Hence, infiltrative growth
      still needs to be verified by operative assessment.

PMID- 23870031
TI  - Re: the impact on sexual function of pelvic organ prolapse surgery.

PMID- 23870032
TI  - What is the impact on sexual function of POP surgery? re: Cao Q, Chen YS, Ding JX
      et al. Long-term treatment outcomes of transvaginal mesh surgery versus anterior
      posterior colporrhaphy for pelvic organ prolapse. Aust N Z J Obstet Gynaecol
      2013; 53: 79-85.

PMID- 23870033
TI  - Downregulation of the endothelial genes Notch1 and ephrinB2 in patients with
      nodular regenerative hyperplasia.
AB  - BACKGROUND & AIMS: Nodular regenerative hyperplasia (NRH) is a rare liver disease
      characterized by small regenerative nodules without fibrosis and can cause portal
      hypertension. Aetiology and pathogenesis of NRH remain unclear. We have recently
      shown that Notch1 knockout induces NRH with portal hypertension through vascular
      remodelling in mice. The aim of this study was to analyse histological and
      clinical data of NRH patients and to explore if the endothelial pathways
      identified in our NRH mouse model are also regulated in human NRH. METHODS:
      Patients were identified retrospectively from the pathology database. Clinical
      and laboratory patient data were retrieved. mRNA expression was measured in liver
      biopsies from a subset of NRH patients. RESULTS: Diagnosis of NRH was confirmed
      in needle biopsies of 51 patients, including 31 patients with grade 1, 12
      patients with grade 2 and 8 patients with grade 3 NRH. Grade 3 nodularity
      significantly correlated with the presence of portal hypertension: 50% of the
      patients with grade 3 NRH vs. 6.5% with grade 1 (P = 0.0105). mRNA expression
      analysis in liver biopsies from 14 NRH patients and in primary human sinusoidal
      endothelial cells revealed downregulation of identical genes as in the murine NRH
      model, which are implicated in vascular differentiation: Notch1, delta-like 4
      (Dll4) and ephrinB2. CONCLUSIONS: In this large NRH needle biopsy cohort, we
      demonstrated that advanced nodularity correlates with presence of portal
      hypertension. Downregulation of the endothelial signalling pathways Dll4/Notch1
      and ephrinB2/EphB4 supports the hypothesis that human NRH is caused by a
      sinusoidal injury providing first insights into the molecular pathogenesis of
      this liver condition.

PMID- 23870034
TI  - Assembly of oppositely charged microgels at the air/water interface.
AB  - We present an assembly of cationic and anionic microgels at the air/water
      interface. Monodispersed, micrometer-sized, and oppositely charged microgels were
      synthesized by aqueous free-radical precipitation polymerization by using N
      isopropylmethacrylamide, comonomers, and cross-linkers. The oppositely charged
      microgels were prepared by using different types of water-soluble initiators.
      These microgels were mixed in a solution to assemble them at the air/water
      interface. In particular, linear and branched chainlike structures of the
      microgels were spontaneously formed at the air/water interface. Effects of salt
      concentration, microgel concentration, and number ratio of cationic and anionic
      microgels on the structures of microgel assembly were investigated by optical
      microscopy and scanning electron microscopy. 

PMID- 23870036
TI  - Investigation of bulk hybrid heterojunction solar cells based on Cu(In,Ga)Se2
      nanocrystals.
AB  - This work presents the systematic studies of bulk hybrid heterojunction solar
      cells based on Cu(In, Ga)Se2 (CIGS) nanocrystals (NCs) embedded in poly(3
      hexylthiophene) matrix. The CIGS NCs of approximately 17 nm in diameter were
      homogeneously blended with P3HT layer to form an active layer of a photovoltaic
      device. The blend ratios of CIGS NCs to P3HT, solvent effects on thin film
      morphologies, interface between P3HT/CIGS NCs and post-production annealing of
      devices were investigated, and the best performance of photovoltaic devices was
      measured under AM 1.5 simulated solar illumination (100 mW/cm2). 

PMID- 23870037
TI  - Bluetongue virus in Lebanon.
AB  - Since 2000, several incursions of bluetongue virus (BTV) occurred in the
      Mediterranean Basin involving European and surrounding Countries. The Middle East
      represents one of the most important gateways for the access of BTV in Europe.
      Limited data on the BTV situation in this area are available. In this
      perspective, an epidemiological survey on the presence of BTV in Lebanon was
      conducted. Of the 181 serum samples tested, 97 (mean = 53.6%; 95% CI: 46.3-60.7)
      resulted positive when tested for the presence of BTV antibodies by c-ELISA, of
      these 42 (mean = 42%; 95% CI: 32.8-51.8) serum samples were from sheep and 55
      (mean = 67.9%; 95% CI: 57.1-77.1) serum samples were from goats. Fourteen blood
      samples (14/110; mean = 12.7%; 95% CI: 7.8-20.3), 6 (6/66; mean = 9.1%; 95% CI:
      4.4-18.5) from sheep and 8 (8/44; mean = 18.2%; 95% CI: 9.6-32.0) from goats,
      were positive by qRT-PCR. The results with serum-neutralization assay and typing
      performed by RT-PCR confirmed that six BTV serotypes are currently circulating in
      Lebanon, and these serotypes are as follows: 1, 4, 6, 8, 16 and 24. This study is
      the first report that confirms the presence and circulation of BTV in Lebanon. 

PMID- 23870035
TI  - Helicobacter pylori downregulates expression of human beta-defensin 1 in the
      gastric mucosa in a type IV secretion-dependent fashion.
AB  - Helicobacter pylori establishes a chronic lifelong infection in the human gastric
      mucosa, which may lead to peptic ulcer disease or gastric adenocarcinoma. The
      human beta-defensins (hbetaDs) are antimicrobial peptides, hbetaD1 being
      constitutively expressed in the human stomach. We hypothesized that H. pylori may
      persist, in part, by downregulating gastric hbetaD1 expression. We measured
      hbetaD1 and hbetaD2 expression in vivo in relation to the presence, density and
      severity of H. pylori infection, investigated differential effects of H. pylori
      virulence factors, and studied underlying signalling mechanisms in vitro.
      Significantly lower hbetaD1 and higher hbetaD2 mRNA and protein concentrations
      were present in gastric biopsies from infected patients. Those patients with
      higher-level bacterial colonization and inflammation had significantly lower
      hbetaD1 expression, but there were no differences in hbetaD2. H. pylori infection
      of human gastric epithelial cell lines also downregulated hbetaD1. Using wild
      type strains and isogenic mutants, we showed that a functional cag pathogenicity
      island-encoded type IV secretion system induced this downregulation. Treatment
      with chemical inhibitors or siRNA revealed that H. pylori usurped NF-kappaB
      signalling to modulate hbetaD1 expression. These data indicate that H. pylori
      downregulates hbetaD1 expression via NF-kappaB signalling, and suggest that this
      may promote bacterial survival and persistence in the gastric niche.

PMID- 23870039
TI  - Letters to the editor: Neurocutaneous melanosis.

PMID- 23870038
TI  - A network-based approach for predicting key enzymes explaining metabolite
      abundance alterations in a disease phenotype.
AB  - BACKGROUND: The study of metabolism has attracted much attention during the last
      years due to its relevance in various diseases. The advance in metabolomics
      platforms allows us to detect an increasing number of metabolites in abnormal
      high/low concentration in a disease phenotype. Finding a mechanistic
      interpretation for these alterations is important to understand
      pathophysiological processes, however it is not an easy task. The availability of
      genome scale metabolic networks and Systems Biology techniques open new avenues
      to address this question. RESULTS: In this article we present a novel
      mathematical framework to find enzymes whose malfunction explains the
      accumulation/depletion of a given metabolite in a disease phenotype. Our approach
      is based on a recently introduced pathway concept termed Carbon Flux Paths
      (CFPs), which extends classical topological definition by including network
      stoichiometry. Using CFPs, we determine the Connectivity Curve of an altered
      metabolite, which allows us to quantify changes in its pathway structure when a
      certain enzyme is removed. The influence of enzyme removal is then ranked and
      used to explain the accumulation/depletion of such metabolite. For illustration,
      we center our study in the accumulation of two metabolites (L-Cystine and
      Homocysteine) found in high concentration in the brain of patients with mental
      disorders. Our results were discussed based on literature and found a good
      agreement with previously reported mechanisms. In addition, we hypothesize a
      novel role of several enzymes for the accumulation of these metabolites, which
      opens new strategies to understand the metabolic processes underlying these
      diseases. CONCLUSIONS: With personalized medicine on the horizon, metabolomic
      platforms are providing us with a vast amount of experimental data for a number
      of complex diseases. Our approach provides a novel apparatus to rationally
      investigate and understand metabolite alterations under disease phenotypes. This
      work contributes to the development of Systems Medicine, whose objective is to
      answer clinical questions based on theoretical methods and high-throughput
      "omics" data.

PMID- 23870040
TI  - An assessment of academic productivity in pediatric neurosurgery.
AB  - OBJECT: Various bibliometric indices are now commonly used to assess academic
      productivity in medicine. Some evidence suggests that these measures are specific
      to subspecialty areas. The authors' goal was to measure the h index of academic
      pediatric neurosurgeons and compare it with previously reported results for
      academic neurosurgeons in general. METHODS: Programs with an Accreditation
      Council for Pediatric Neurosurgery Fellowships-approved fellowship were
      identified, and the h and g indices of each of their surgeons were calculated.
      These were correlated with academic rank and compared with published literature
      on academic neurosurgical departments. RESULTS: Seventy-two pediatric
      neurosurgeons had a mean h index of 16.6 and a mean g index of 29.5. Both indices
      increased with progressive academic rank. The rank-specific mean index for
      academic pediatric neurosurgeons was similar to that of neurosurgeons from
      academic departments in general. CONCLUSIONS: Overall, the authors conclude that
      the h index metric is a reasonable measure of academic productivity in the
      pediatric neurosurgery arena that provides a robust measure of an individual's
      contribution to the pediatric neurosurgery literature. Like its counterpart in
      neurosurgery in general, the h index for pediatric neurosurgeons correlates with
      institutional rank. The h index calculation also reveals the productivity of the
      pediatric neurosurgeons to be on par with the productivity of neurosurgeons in
      general.

PMID- 23870041
TI  - Neurosurgical treatment of oligodendroglial tumors in children and adolescents: a
      single-institution series of 35 consecutive patients.
AB  - OBJECT: The object of this study was to delineate long-term results of the
      surgical treatment of pediatric CNS tumors classified as oligodendroglioma (OD)
      or oligoastrocytoma (OA) WHO Grade II or III. METHODS: A cohort of 45 consecutive
      patients 19 years or younger who had undergone primary resection of CNS tumors
      originally described as oligodendroglial during the years 1970-2009 at a single
      institution were reviewed in this retrospective study of surgical morbidity,
      mortality, and academic achievement and/or work participation. Gross motor
      function and activities of daily living were scored using the Barthel Index (BI).
      RESULTS: Patient records for 35 consecutive children and adolescents who had
      undergone resection for an OA (17 patients) or OD (18 patients) were included in
      this study. Of the 35 patients, 12 were in the 1st decade of life at the first
      surgery, whereas 23 were in the 2nd decade. The male/female ratio was 1.19
      (19/16). No patient was lost to follow-up. The tumor was localized to the
      supratentorial compartment in 33 patients, the posterior fossa in 1 patient, and
      the cervical medulla in 1 patient. Twenty-four tumors were considered to be WHO
      Grade II, and 11 were classified as WHO Grade III. Among these latter lesions
      were 2 tumors initially classified as WHO Grade II and later reclassified as WHO
      Grade III following repeat surgery. Fifty-four tumor resections were performed.
      Two patients underwent repeat tumor resection within 5 days of the initial
      procedure, after MRI confirmed residual tumor. Another 10 patients underwent a
      second resection because of clinical deterioration and progressive disease at
      time points ranging from 1 month to 10 years after the initial operation. Six
      patients underwent a third resection, and 1 patient underwent a fourth excision
      following tumor dissemination to the spinal canal. Sixteen (46%) of the 35
      children received adjuvant therapy: 7, fractionated radiotherapy; 4,
      chemotherapy; and 5, both fractionated radiotherapy and chemotherapy. One patient
      with primary supratentorial disease experienced clinically malignant development
      with widespread intraspinal dissemination 9 years after initial treatment. Only 2
      patients needed treatment for persistent hydrocephalus. In this series there was
      no surgical mortality, which was defined as death within 30 days of resection.
      However, 12 patients in the study, with follow-up times from 1 month to 33 years,
      died. Twenty-three patients, with follow-up times from 4 to 31 years, remained
      alive. Among these survivors, the BI was 100 (normal) in 22 patients and 80 in 1
      patient. Nineteen patients had full- or part-time work or were in normal school
      programs. CONCLUSIONS: Pediatric oligodendroglial tumors are mainly localized to
      the supratentorial compartment and more often occur in the 2nd decade of life
      rather than the 1st. Two-thirds of the patients remained alive after follow-ups
      from 4 to 31 years. Twelve children succumbed to their disease, 9 of them within
      3 years of resection despite combined treatment with radio- and chemotherapy.
      Three of them remained alive from 9 to 33 years after primary resection. Among
      the 23 survivors, a stable, very long-term result was attainable in at least 20.
      Five-, 10-, 20-, and 30-year overall survival in patients with Grade II tumors
      was 92%, 92%, 92%, and 88%, respectively.

PMID- 23870042
TI  - Persistence with first line anticholinergic medication in treatment-naive
      overactive bladder patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the persistence of first line
      anticholinergic medication use by patients with overactive bladder (OAB). Data
      from a hospital outpatient database were matched with information obtained by a
      telephone survey of patients to determine which patients discontinued use of
      anticholinergic medication and to identify the reasons underlying
      discontinuation. MATERIAL AND METHODS: The study group included 377 OAB patients
      (52 men, 325 women) with a mean age of 60.29 +/- 13.84 years. In total, 189
      patients (50.1%) were treated with trospium (median dose 27.86 +/- 12.73 mg), 41
      patients (10.9%) with propiverine (28.17 +/- 4.97 mg), nine patients (2.4%) with
      extended-release tolterodine (4.0 +/- 0 mg), 48 patients (12.7%) with solifenacin
      (5.94 +/- 1.97 mg) and 90 patients (23.9%) with fesoterodine (6.09 +/- 2.01 mg).
      RESULTS: The median time for persistence with the first line anticholinergic
      treatment was 6.53 +/- 3.84 months. Persistence was significantly higher in
      patients treated with anticholinergic medication with an extended-release
      formulation than in patients treated with immediate-release anticholinergics. The
      most common reasons for termination of treatment were healing/resolution of
      symptoms (35.9%), low effectiveness (30.9%) and side-effects (23.7%).
      CONCLUSIONS: More than half of the OAB patients were not satisfied with their
      first line treatment. Other treatment options should be sought, such as changing
      the medication or dosage, or possibly combining treatments.

PMID- 23870043
TI  - Facial skin breakdown in patients with non-invasive ventilation devices: report
      of two cases and indications for treatment and prevention.
AB  - Non-invasive ventilation (NIV) provides an effective ventilatory support in
      patients with respiratory failure without endotracheal intubation. However, there
      are potential problems with its clinical application and the development of
      pressure ulcers represents a common complication. Often several intensive care
      units treat facial skin breakdown related to NIV. In this article, we report our
      experience in treatment and prevention of these lesions, emphasising the higher
      risk of certain age groups to develop them, such as preterm infants and elderly
      patients with comorbidities. We performed daily disinfection of the lesions
      followed by application of topical cream containing hyaluronic acid (HA) sodium
      salt. In addition, in order to prevent worsening of injury, we applied a cushion
      made of gauze pad containing HA sodium salt between the skin and the masks, so as
      to reduce friction between the NIV devices and the skin. Local medical treatment
      allowed complete reepithelialisation of the injured skin areas. Systematic
      monitoring of patients' faces is essential to detect early damages and to
      intervene with appropriate therapy, especially in preterm infants and elderly.
      Moreover, refining the devices with the proposed protective cushion can reduce
      pressure ulcers and increase comfort for the patients. 

PMID- 23870044
TI  - Effect of conjugated linoleic acid and vitamin E on glycemic control, body
      composition, and inflammatory markers in overweight type2 diabetics.
AB  - BACKGROUND: The healthy properties of conjugated linoleic acid (CLA) such as
      weight loss, reducing cardiovascular risk factors and inflammation have been
      reported. The trans-10, cis-12 CLA isomer is related to increasing insulin
      resistance, but the effects of cis-9, trans-11 isomer is not clear. The aim of
      this study was to investigate the effects of CLA with and without Vitamin E on
      body weight, body composition, glycemic index, inflammatory and coagulation
      factors, lipid profile, serum leptin and adiponectin, malondialdehyde (MDA), and
      blood pressure in type2 diabetes. METHODS: 56 patients with type2 diabetes were
      included in 8 week double-blind control trial that used metformin. They randomly
      divided into three groups: CLA + VitE, CLA + VitE placebo, CLA placebo + VitE
      placebo. All variables, anthropometric measurements, and body composition were
      evaluated at the beginning and the end of study. Statistical analysis and
      analysis of dietary data were performed using SPSS and nutritionist IV software,
      respectively. RESULTS: There were not any significant differences in variable
      changes among three groups. However, there was a trend to increase in MDA and
      decrease in apoB100 among CLA consumers. CONCLUSION: The results of this study
      showed that administration of CLA supplementation for 8 weeks does not affect any
      indicators of metabolic control in overweight type2 diabetic patients.

PMID- 23870045
TI  - Lost in translation--the role of family in interventions among adults with
      diabetes: a systematic review.
AB  - AIMS: Family interventions are increasingly recognized as important in the care
      of people with diabetes. The aim of this study was to synthesize the existing
      literature on family interventions among adults with Type 1 and Type 2 diabetes
      and to determine the degree to which they were family centred. METHODS: The
      literature search was carried out in four databases (Scopus, CINAHL, PsycINFO and
      ERIC). Two reviewers independently screened the search results. Only English
      language articles about interventions on education, care and/or support of adult
      individuals with diabetes involving the participation of both the individual with
      diabetes and at least one family member were included. RESULTS: From an initial
      1480 citations, 10 reports were included. The intervention studies varied
      considerably in terms of design and population. The family dimension generally
      represented a modest part of the interventions: Two interventions applied a
      family-relevant theoretical framework. Disease knowledge and lifestyle changes
      were more prevalent intervention themes than family issues. Biological and
      behavioural outcomes were most prevalent, whereas psychosocial and family
      outcomes were used in six of the studies. CONCLUSIONS: The number of trials and
      statistically significant results in family interventions targeting adults with
      diabetes is limited. Because of inhomogeneity, it is difficult to come to a
      conclusion on effective approaches in family interventions. The interventions are
      inconsistent with regard to theoretical framework, intervention themes and
      measured outcomes. However, psychosocial and familial dimensions seem sensitive
      to family-based interventions. From development to evaluation, the family
      dimension needs to be included to prove the specific effect of family
      interventions.

PMID- 23870046
TI  - Evaluating interactive videoconferencing for assessing symptoms of autism.
AB  - BACKGROUND: Autism affects as many as 1 in 88 children. Best practices recommend
      early identification and intervention for optimal outcomes. Currently, a gap
      exists between time of first concern and diagnosis, particularly for families
      living in rural areas. Telemedicine as a tool for assessment and diagnosis of
      autism is one way to address this disparity. Emerging evidence suggests
      telemedicine as a viable option for assessing children with a variety of special
      needs. MATERIALS AND METHODS: This study expands upon the current literature by
      investigating clinicians' ability to assess autism via telemedicine. Using
      interactive videoconferencing, we simulated autism assessment procedures with
      families with an existing diagnosis (autism or developmental disability) using
      current gold-standard assessment tools. We compared diagnostic accuracy, item-by
      item reliability on the Autism Diagnostic Observation Schedule (ADOS)-Module 1,
      and the Autism Diagnostic Interview-Revised (ADI-R) as well as parent
      satisfaction in an in-person and interactive videoconferencing condition. Ten
      children (3-5 years old) with developmental delays and 11 children matched on
      chronological age with a diagnosis of autism were assigned to be assessed and
      interviewed either in-person or over videoconferencing. Clinicians observed both
      in-person and through videoconferencing regardless of patient assignment.
      RESULTS: Results indicated no significant difference in reliability of diagnostic
      accuracy, ADOS observations, ratings for ADI-R parent report of symptoms, and
      parent satisfaction between conditions. Results indicate adequate clinician
      agreement and parent satisfaction regardless of observational condition.
      CONCLUSIONS: Future research should include a larger sample size and assess
      children without an existing diagnosis.

PMID- 23870047
TI  - Faked depression: comparing malingering via the internet, pen-and-paper, and
      telephone administration modes.
AB  - BACKGROUND: The Internet and telephone are valuable resources for mental health
      practitioners when access to face-to-face assessment or therapy is difficult.
      However, despite the high stakes (such as access to medication or financial
      compensation) often involved in psychological testing, little is known about how
      test administration mode influences test scores when patients are malingering.
      The aim of this research was to examine for the first time the equivalence of a
      malingered measure of depression when administered over the Internet, over the
      telephone, and with pen and paper. SUBJECTS AND METHODS: A mixed experimental
      design was used with participants (n=91) randomly allocated to Internet,
      telephone, or pen-and-paper groups. Participants completed the Edinburgh
      Depression Scale, first under standard instructions and then under instructions
      to fake as if experiencing severe depression. A manipulation check was included
      to ensure participants had understood and followed instructions to fake. RESULTS:
      As predicted, participants were able to significantly increase their depression
      scores when asked to fake depression. Participants reported significantly lower
      faked depression scores over the telephone than in pen-and-paper format. Faked
      depression scores in the online group did not differ significantly from those in
      the telephone and pen-and-paper groups. However, participants in all groups met
      criteria indicative of a provisional diagnosis of depression. CONCLUSIONS:
      Overall, the results indicate that there may be no meaningful difference between
      malingering across administration modes. If an individual is malingering
      depression, administration mode has minimal influence. These findings provide
      preliminary support for the use of online/telephone technologies in the
      assessment of depression.

PMID- 23870048
TI  - Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen
      associated acute liver failure.
AB  - BACKGROUND: An acetominophen overdose (AOD) is the leading cause of acute liver
      failure (ALF) in the UK and USA. For patients who meet the King's College
      Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver
      transplantation (OLT) is conventionally performed with subsequent life-long
      immunosuppression. A new technique was developed in 1998 for AOD-induced ALF
      where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft
      auxiliary liver transplant (WGALT) was performed with complete withdrawal of
      immunosupression during the first year post-operatively. RESULTS: During 1998
      2010, 68 patients were listed for an emergency transplantation for AOD ALF at our
      institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with
      WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5
      years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off
      immunosuppression. Poor prognostic factors in the WGALT group included higher
      donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion
      (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54 kg, P = 0.036).
      CONCLUSION: Although OLT remains standard practice for AOD-induced ALF, life-long
      immunosuppression is required. A favourable survival rate using a subtotal
      hepatectomy and WGALT has been demonstrated, and importantly, all successful
      patients have undergone complete immunosuppression withdrawal. This technique is
      advocated for patients who have acetominophen hepatotoxicity requiring liver
      transplantation.

PMID- 23870050
TI  - Commentary: Significant differences in nonmelanoma skin cancers of the upper and
      lower lip.

PMID- 23870049
TI  - Temporal analysis of attentional processes in spontaneous interactions between
      people with profound intellectual and multiple disabilities and their support
      workers.
AB  - BACKGROUND: Few studies examined joint attention in interactions with people with
      profound intellectual and multiple disabilities (PIMD), although being an
      important component of high-quality interaction. The purpose of this study is to
      describe initiating joint attention behaviour from people with PIMD and their
      support workers as well as the sequential relationship between initiating joint
      attention behaviour and attention episodes in spontaneous interactions. METHOD:
      Video observations of 28 support worker-client dyads were coded using partial
      interval coding. RESULTS: Results show much variation across persons and dyads.
      Within the support worker-client dyad, there is not much joint attention but
      shared attention is frequently occurring. In general, people with PIMD are
      directing the attention of their interaction partner at low rates. The support
      workers are frequently directing the attention of the clients towards a topic of
      interest but not often through the tactile modality. The occurrence of an
      attention episode cannot be predicted on the basis of preceding initiating joint
      attention behaviour of the interaction partners. CONCLUSION: This study presents
      directions for future research and implications for practice. It may increase
      support workers' knowledge of their own contributions, strengths and weaknesses
      in directing and maintaining attention within interactions with people with PIMD.

PMID- 23870051
TI  - Variable mycorrhizal benefits on the reproductive output of Geranium sylvaticum,
      with special emphasis on the intermediate phenotype.
AB  - In several gynodioecious species, intermediate sex between female and
      hermaphrodite has been reported, but few studies have investigated fitness
      parameters of this intermediate phenotype. Here, we examined the interactions
      between plant sex and arbuscular mycorrhizal (AM) fungal species affecting the
      reproductive output of Geranium sylvaticum, a sexually polymorphic plant species
      with frequent intermediate sexes between females and hermaphrodites, using a
      common garden experiment. Flowering phenology, AM colonisation levels and several
      plant vegetative and reproductive parameters, including seed and pollen
      production, were measured. Differences among sexes were detected in flowering,
      fruit set, pollen production and floral size. The two AM species used in the
      present work had different effects on plant fitness parameters. One AM species
      increased female fitness through increasing seed number and seed mass, while the
      other species reduced seed mass in all sexes investigated. AM fungi did not
      affect intermediate and hermaphrodite pollen content in anthers. The three sexes
      in G. sylvaticum did not differ in their reproductive output in terms of total
      seed production, but hermaphrodites had potentially larger fathering ability than
      intermediates due to higher anther number. The ultimate female function--seed
      production--did not differ among the sexes, but one of the AM fungi used
      potentially decreased host plant fitness. In addition, in the intermediate sex,
      mycorrhizal symbiosis functioned similarly in females as in hermaphrodites.

PMID- 23870053
TI  - Robot-assisted transumbilical laparoendoscopic single-site pyeloplasty: technique
      and perioperative outcomes from a single institution.
AB  - INTRODUCTION: Transumbilical laparoendoscopic single-site (U-LESS) pyeloplasty
      may provide improved cosmesis compared with conventional laparoscopic
      pyeloplasty. However, U-LESS pyeloplasty can be challenging because of the need
      for extensive suturing. The wristed instrumentation of robot-assisted
      laparoendoscopic single-site (R-LESS) pyeloplasty provides improved dexterity to
      facilitate intracorporeal suturing. We therefore present our technique and
      experience with R-LESS pyeloplasty for ureteropelvic junction obstruction (UPJO).
      SUBJECTS AND METHODS: The da Vinci((r)) S or Si Surgical System (Intuitive
      Surgical, Sunnyvale, CA) was used in all cases. Ureteral stents were placed
      cystoscopically at the start of each case. A 3-cm skin incision was made adjacent
      to the umbilicus. Three ports (12 mm, 8 mm, and 5 mm) were placed either through
      separate fascial incisions or into a GelPort((r)) (Applied Medical, Rancho Santa
      Margarita, CA). Key techniques included port staggering, a "chopstick"
      arrangement of the instruments, and use of a 30 degrees  lens in an upward
      configuration. Traditional dismembered pyeloplasty procedures were performed in
      all cases. Patients less than 45 years of age with no prior abdominal surgery
      were offered this approach. RESULTS: Eight patients (4 female; 5 right-sided;
      median age, 22 years) underwent R-LESS pyeloplasty without the need for
      additional ports. All patients were discharged by the third postoperative day,
      and 5 were discharged on Day 1. One patient experienced urine leakage, which was
      managed with a temporary nephrostomy tube. Length of follow-up ranged from 29 to
      46 months. No patients have developed symptoms or radiographic evidence of
      recurrent UPJO. CONCLUSIONS: R-LESS pyeloplasty can be safely performed for
      selected patients with currently available robotic equipment. Careful patient
      selection and case setup are key to successfully performing these procedures.

PMID- 23870052
TI  - Endothelial transdifferentiation in hepatocellular carcinoma: loss of Stabilin-2
      expression in peri-tumourous liver correlates with increased survival.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a malignant tumour that is
      characterized by extensive vascular remodelling and responsiveness to treatment
      with the anti-angiogenic multikinase inhibitor sorafenib. The aim was to study
      endothelial remodelling in HCC. METHODS: The murine inducible albumin-SV40-large
      T-antigen model and two tissue microarrays (TMA) with 295 tumourous and 83 peri
      tumourous samples of 296 patients with HCC were analysed for expression of liver
      sinusoidal endothelial cell (LSEC)-specific marker proteins, stabilin-1 and
      stabilin-2, LYVE-1 and CD32b. RESULTS: LSEC marker proteins were sequentially
      lost during HCC progression in the murine HCC model being absent from tumour
      nodules larger than 800 MUm in diameter. Similarly, the TMA analysis of human
      HCCs revealed loss of all four marker proteins in the majority of tumourous
      tissue samples. Preservation of LYVE-1 expression showed a significant
      correlation with low grading (G1). In corresponding peri-tumourous liver tissue,
      loss of all marker proteins was seen in a minor proportion of cases (34%) while
      the majority of cases retained expression of at least one of the marker proteins.
      Loss of stabilin-2 expression in peri-tumourous liver tissue of patients with HCC
      was significantly less likely to occur (38%) than loss of the other marker
      proteins (63-95%) and it was associated with significantly longer tumour-specific
      (P = 0.0523) and overall (P = 0.0338) survival. Loss of stabilin-2 may enhance
      survival in HCC by preventing endothelial-tumour cell adhesive interactions and
      microvascular invasion. CONCLUSIONS: In summary, endothelial transdifferentiation
      is a major pathogenic event in HCC development indicating a switch from vessel co
      option/intussusceptive angiogenesis to sprouting angiogenesis.

PMID- 23870054
TI  - Transoral extraction of a laparoscopically resected large gastric GIST.
AB  - Although natural orifice specimen extraction is now widely performed, there have
      been no reports of transoral extraction following laparoscopic gastric resection.
      This report describes the first transoral specimen extraction in a patient with a
      gastrointestinal stromal tumor (GIST) of the lesser curvature of the stomach. The
      clinical data of a patient with a large gastric GIST were reviewed. Totally
      laparoscopic resection of the gastric lesser curvature was performed using four
      trocars. The specimen, put in a retrieval bag, was withdrawn via the transgastric
      and esophageal route. Reconstruction of the stomach was performed using the
      intracorporeal technique. The procedure was successfully accomplished without
      intraoperative and postoperative complications. In conclusion, transoral specimen
      extraction after laparoscopic gastric resection is a safe and feasible operative
      procedure for selected patients with a large benign gastric tumor.

PMID- 23870055
TI  - Systemic retinoids for the chemoprevention of cutaneous squamous cell carcinoma
      and verrucal keratosis in a cohort of patients on BRAF inhibitors.
AB  - BACKGROUND: The treatment of metastatic melanoma has changed greatly with the
      development of inhibitors targeted at the mutated BRAF kinase present in up to
      50% of metastatic melanoma cases. These agents, vemurafenib and dabrafenib, have
      been shown to increase median survival. Unfortunately, they have also been
      associated with the development of verrucal keratosis (VK) and cutaneous squamous
      cell carcinoma (cuSCC). These lesions require surgical excision, and when a large
      number of these lesions need to be treated, it can significantly affect the
      patient's quality of life. OBJECTIVES: To determine if acitretin is suitable as a
      chemopreventative agent against the development of verrucal keratosis and cuSCC,
      in patients on BRAF inhibitors. METHODS: Patients treated with a BRAF inhibitor,
      vemurafenib or dabrafenib, for stage IV metastatic melanoma, who had undergone
      more than five surgical excisions to remove lesions suggestive of cuSCC, were
      offered the opportunity to commence acitretin as a chemopreventative agent.
      Patients were evaluated every 4 weeks. Clinical and histological data were
      collected. RESULTS: Eight patients, who had a total of 24 cuSCC removed, were
      included in the study. After commencement of acitretin, only five cuSCC were
      excised from two patients. The most significant reduction was in a patient who
      had developed 13 cuSCC over 10 months and only two cuSCC 3 months after
      commencing acitretin. No modifications in the dose of the BRAF inhibitor were
      made as a result of cuSCC in any of these patients. CONCLUSIONS: Acitretin should
      be considered as a chemopreventative agent for VK and cuSCC in patients taking
      BRAF inhibitors, before considering dosage reductions.

PMID- 23870056
TI  - Two new ent-kaurane diterpenoids from Pteris semipinnata.
AB  - In this study, two new compounds and six known compounds were isolated from the
      aerial parts of Pteris semipinnata. The chemical structures of these two new
      compounds were elucidated as 6beta,11alpha-dihydroxy-15-oxo-ent-kaur-16-en-19-oic
      acid (1) and 7alpha,11alpha-dihydroxy-15-oxo-ent-kaur-16-en-19-oic acid (2) by
      the extensive spectral methods including 2D NMR and HR-MS techniques. 

PMID- 23870057
TI  - The recruitment of p47(phox) and Rac2G12V at the phagosome is transient and
      phosphatidylserine dependent.
AB  - BACKGROUND INFORMATION: During phagocytosis, neutrophils internalise pathogens in
      a phagosome and produce reactive oxygen species (ROS) by the NADPH oxidase to
      kill the pathogen. The cytosolic NADPH oxidase subunits p40(phox), p47(phox),
      p67(phox) and Rac2 translocate to the phagosomal membrane to participate in
      enzyme activation. The kinetics of this recruitment and the underlying signalling
      pathways are only partially understood. Anionic phospholipids, phosphatidylserine
      (PS) and phosphoinositides (PPI) provide an important attachment site for
      numerous proteins, including several oxidase subunits. RESULTS: We investigated
      the kinetics of p47(phox) and Rac2 phagosomal membrane recruitment. Both subunits
      are known to interact with anionic phospholipids; we therefore addressed the role
      of PS in this recruitment. Phagosomal accumulation of p47(phox) and Rac2 tagged
      with fluorescent proteins was analysed by videomicroscopy. We used the C2 domain
      of lactadherin (lactC2) that interacts strongly and specifically with PS to
      monitor intracellular PS localisation and to decrease PS accessibility. During
      phagocytosis of opsonised zymosan, p47(phox) and constitutively active Rac2G12V
      briefly translocated to the phagosomal membrane, whereas ROS production continued
      for a longer period. However, in the presence of lactC2, Rac2G12V recruitment was
      inhibited and the kinetics of p47(phox) recruitment and detachment were delayed.
      A reduced phagosomal ROS production was also observed during the first 7 min
      following the phagosome closure. CONCLUSIONS: These results suggest that
      p47(phox) and Rac2 accumulate only transiently at the phagosome at the onset of
      NADPH activity and detach from the phagosome before the end of ROS production.
      Furthermore, lactC2, by masking PS, interfered with the phagosomal recruitment of
      p47(phox) and Rac2 and disturbed NADPH oxidase activity. Thus, PS appears as a
      modulator of NADPH oxidase activation.

PMID- 23870058
TI  - High prevalence of asthma symptoms in Warao Amerindian children in Venezuela is
      significantly associated with open-fire cooking: a cross-sectional observational
      study.
AB  - BACKGROUND: The International Study on Asthma and Allergies in Childhood (ISAAC)
      reported a prevalence of asthma symptoms in 17 centers in nine Latin American
      countries that was similar to prevalence rates reported in non-tropical
      countries. It has been proposed that the continuous exposure to infectious
      diseases in rural populations residing in tropical areas leads to a relatively
      low prevalence of asthma symptoms. As almost a quarter of Latin American people
      live in rural tropical areas, the encountered high prevalence of asthma symptoms
      is remarkable. Wood smoke exposure and environmental tobacco smoke have been
      identified as possible risk factors for having asthma symptoms. METHODS: We
      performed a cross-sectional observational study from June 1, 2012 to September
      30, 2012 in which we interviewed parents and guardians of Warao Amerindian
      children from Venezuela. Asthma symptoms were defined according to the ISAAC
      definition as self-reported wheezing in the last 12 months. The associations
      between wood smoke exposure and environmental tobacco smoke and the prevalence of
      asthma symptoms were calculated by means of univariate and multivariable logistic
      regression analyses. RESULTS: We included 630 children between two and ten years
      of age. Asthma symptoms were recorded in 164 of these children (26%). The
      prevalence of asthma symptoms was associated with the cooking method. Children
      exposed to the smoke produced by cooking on open wood fires were at higher risk
      of having asthma symptoms compared to children exposed to cooking with gas (AOR
      2.12, 95% CI 1.18 - 3.84). Four percent of the children lived in a household
      where more than ten cigarettes were smoked per day and they had a higher risk of
      having asthma symptoms compared to children who were not exposed to cigarette
      smoke (AOR 2.69, 95% CI 1.11 - 6.48). CONCLUSION: Our findings suggest that
      children living in rural settings in a household where wood is used for cooking
      or where more than ten cigarettes are smoked daily have a higher risk of having
      asthma symptoms.

PMID- 23870059
TI  - Hydroalcoholic extract of Urtica circularis: a neuropharmacological profile.
AB  - CONTEXT: The genus Urtica has been known since ancient times. It has known to be
      useful for the treatment of different human ailments. OBJECTIVE: The present work
      evaluated the neuropharmacological effects of a hydroalcoholic extract of Urtica
      circularis (Hicken) Soraru (Urticaceae). materials and method: The effect on
      central nervous system of U. circularis hydroalcoholic extract (from leaves and
      stems) administered by the intraperitoneal route in mice was evaluated by several
      tests: Pentobarbital- and midazolam-induced hypnosis, open field, hole board,
      elevated plus-maze and forced swimming. Phytochemical analysis was performed by
      high-performance liquid chromatography. RESULTS: A total of 300 mg/kg i.p. of the
      extract produced a significant prolongation of pentobarbital- (40 mg/kg i.p.;
      60.1 min versus 25.4 min) and midazolam- (50 mg/kg i.v.; 53.4 min versus 25.1
      min) induced sleeping time. The extract's administration caused a marked
      reduction of the head-dipping response (DE50: 373 mg/kg i.p.) in the hole-board
      test. Urtica circularis extract (DE50: 46 mg/kg i.p.) reduced the spontaneous
      locomotor activity in the open field test. Flumazenil and atropine significantly
      antagonized the extract's effect on the locomotor activity. No motor coordination
      disturbance was observed in the rota rod test at any doses. In the forced
      swimming test, the extract did not produce any change in the immobility time and
      it had no significant effects in elevated plus maze test. The phytochemical
      analysis revealed the presence of chlorogenic acid, vanillic acid, caffeic acid,
      vicenin-2, p-cumaric acid, ferulic acid, vitexin and isovitexin. CONCLUSION: This
      study revealed that U. circularis hydroalcoholic extract possesses sedative
      activity, facilitating GABAergic and cholinergic transmission.

PMID- 23870060
TI  - Molecular approaches to transfusion medicine in Polynesians and Maori in New
      Zealand.
AB  - In recent years, with the application of genotyping technology, there has been a
      substantial increase in the number of reported blood group alleles. This survey
      was designed to evaluate new molecular blood group genotyping methods and compile
      reference blood group data sets for Polynesian and Maori subjects. Subsequent
      analyses of these results were used to calculate probability of random match, to
      trace Polynesian ancestry and migration patterns and to reveal past and present
      episodes of genetic admixture. Genomic DNA samples from Maori and Polynesian
      subjects were drawn from the Victoria University of Wellington DNA Bank and
      genotyped using combination of commercial PCR-SSP kits, hybridization SNP assay
      services or sequence-based typing. This survey also involves compilation of
      serological ABO and Rhesus blood group data from RakaiPaaka Iwi tribal members
      for comparison with those generated during our molecular blood group study. We
      observed perfect consistency between results obtained from all molecular methods
      for blood group genotyping. The A, O, DCcEe, DCCee, MNs, K-k+, Jk(a+b-),
      Jk(a+b+), Fy(a+b-), Fy(a+b+), Di(a+b-), Co(a+b-) and Do(a-b+) were predominant
      blood group phenotypes in both Polynesians and Maori. Overall, our survey data
      show only small differences in distributions of blood group phenotypes between
      Polynesian and Maori groups and their subgroups. These differences might be
      associated with selection, population history and gene flow from Europeans. In
      each case, we estimate that patients with certain blood groups have a very low
      probability of an exact phenotypic match, even if the patients were randomly
      transfused with blood from donors of their own ethnicity. The best way to avoid
      haemolytic transfusion reaction in such cases is to perform a pretransfusion
      cross-match and recruit increased numbers of donors with rare phenotype profiles.
      The conclusion of this study is that application of molecular method covering as
      many known variants as possible may help to improve the accuracy blood group
      genotyping and potentially conserve the routine requirements of transfusion
      centres. 

PMID- 23870061
TI  - Fano effect and bound state in continuum in electron transport through an
      armchair graphene nanoribbon with line defect.
AB  - : Electron transport properties in an armchair graphene nanoribbon are
      theoretically investigated by considering the presence of line defect. It is
      found that the line defect causes the abundant Fano effects and bound state in
      continuum (BIC) in the electron transport process, which are tightly dependent on
      the width of the nanoribbon. By plotting the spectra of the density of electron
      states of the line defect, we see that the line defect induces some localized
      quantum states around the Dirac point and that the different localizations of
      these states lead to these two kinds of transport results. Next, the Fano effect
      and BIC phenomenon are detailedly described via the analysis about the influence
      of the structure parameters. According to the numerical results, we propose such
      a structure to be a promising candidate for graphene nanoswitch. PACS: 81.05.Uw,
      71.55.-i, 73.23.-b, 73.25.+i. 

PMID- 23870062
TI  - Sergentomyia (Neophlebotomus) gemmea, a potential vector of Leishmania siamensis
      in southern Thailand.
AB  - BACKGROUND: Leishmaniasis, caused by Leishmania siamensis, is an emerging disease
      in Thailand. Although reported cases have been increasing, epidemiological
      information of the disease including host and vector aspects is not clearly
      known. This study was a preliminary survey of the potential vector of L.
      siamensis in an affected area of leishmaniasis, Trang Province, southern
      Thailand. METHODS: The collection of sandflies was performed around the area
      where a case of leishmaniasis was reported using CDC light traps. Species of
      sandfly were identified based on morphological characteristics according to
      Lewis's key. PCR amplification and sequencing of the heat shock protein 70 gene
      (hsp70) was used to identify L. siamensis DNA in sandflies. RESULTS: A total of
      146 male and female sandflies were collected in the affected areas. Of 71 female
      sandflies, four species were identified, i.e., Sergentomyia (Neophlebotomus)
      gemmea, S. (Neophlebotomus) iyengari, S. (Parrotomyia) barraudi and Phlebotomus
      (Anaphlebotomus) stantoni. Among these species, S. (Neophlebotomus) gemmea was
      the most predominant species in all areas. DNA of L. siamensis was identified in
      S. (Neophlebotomus) gemmea. Nucleotide sequences of PCR products using DNA
      extracted from S. (Neophlebotomus) gemmea showed 99.8% identity to L. siamensis.
      CONCLUSION: S. (Neophlebotomus) gemmea might be a potential vector of L.
      siamensis in an affected area, Trang Province, southern Thailand. However further
      studies are needed to prove whether these sandflies can be natural vectors of
      leishmaniasis.

PMID- 23870063
TI  - Multifaceted responses to two major parasites in the honey bee (Apis mellifera).
AB  - The recent declines in managed honey bee populations are of scientific,
      ecological and economic concern, and are partially attributed to honey bee
      parasites and related disease. McDonnell et al. investigate behavioral, chemical
      and neurogenomic effects of parasitization by the ectoparasite Varroa destructor
      and the endoparasite Nosema ceranae. The study reveals important links between
      underlying mechanisms of immunity and parasitization in social insects by
      demonstrating that chemical signals and neurogenomic states are significantly
      different between parasitized and non-parasitized honey bees, and that
      neurogenomic states are partially conserved between bees infected with distinct
      parasites. However the study does not reveal whether differences measured are
      primarily the result of adaptive host responses or of manipulation of the honey
      bee host by the parasites and/or confounding viral loads of parasitized
      individuals. Questions answered and raised by McDonnell et al. will lead to an
      improved understanding of honey bee health and, more generally, host-parasite
      interactions.

PMID- 23870064
TI  - Annular telangiectatic perivascular angiomatosis: a paradoxical adverse event of
      propranolol.

PMID- 23870065
TI  - Development and evaluation of loop-mediated isothermal amplification (LAMP) for
      rapid detection of Clonorchis sinensis from its first intermediate hosts,
      freshwater snails.
AB  - Clonorchiasis, caused by Clonorchis sinensis, is a key foodborne zoonosis, which
      is mainly found in China, Korea and Vietnam. Detection of this parasite from the
      second intermediate host, the freshwater fish is the common method for
      epidemiological surveys of this parasite, but is time consuming, labour intensive
      and easily leads to misdiagnosis. In this study, we have developed a rapid,
      sensitive and reliable molecular method for the diagnosis of C. sinensis from its
      first intermediate hosts, freshwater snails, based on a loop-mediated isothermal
      amplification (LAMP) method. The specific amplified fragment from genomic DNA of
      C. sinensis did not cross-react with those from other relevant trematodes and a
      range of hosts (freshwater fish, shrimps and snails) of C. sinensis living in
      similar environments. The detection limit of the LAMP method was as low as 10 fg
      which was 1000 times more sensitive than conventional PCR, which was also
      demonstrated by successful application to field samples. These results show that
      the LAMP method is a more sensitive tool than conventional PCR for the detection
      of C. sinensis infection in the first intermediate hosts and, due to a simpler
      protocol, is an ideal molecular method for field-based epidemiological surveys of
      this parasite.

PMID- 23870066
TI  - Speech technology and cinema: can they learn from each other?
AB  - The voice is the most important sound of a film soundtrack. It represents a
      character and it carries language. There are different types of cinematic voices:
      dialogue, internal monologues, and voice-overs. Conventionally, two main
      characteristics differentiate these voices: lip synchronization and the voice's
      attributes that make it appropriate for the character (for example, a voice that
      sounds very close to the audience can be appropriate for a narrator, but not for
      an onscreen character). What happens, then, if a film character can only speak
      through an asynchronous machine that produces a 'robot-like' voice? This article
      discusses the sound-related work and experimentation done by the author for the
      short film Voice by Choice. It also attempts to discover whether speech
      technology design can learn from its cinematic representation, and if such
      uncommon film protagonists can contribute creatively to transform the conventions
      of cinematic voices.

PMID- 23870067
TI  - Role of FDFT1 polymorphism for fibrosis progression in patients with chronic
      hepatitis C.
AB  - BACKGROUND: In chronic hepatitis C (CHC), steatosis is associated with fibrosis
      and impaired response to antiviral therapy. Recently, a polymorphism of single
      nucleotide polymorphism SNP rs2645424 of farnesyl diphosphate farnesyl
      transferase 1 (FDFT1) was identified in NAFLD/NASH as a possible causal link to
      steatosis and fibrosis progression. SNP rs738409 in the adiponutrin gene (PNPLA3)
      is a well described factor for steatosis. This study evaluated the relation of
      these SNPs on steatosis, fibrosis and treatment response in CHC. METHODS: The
      SNPs rs738409478 and rs2645424 were determined by real-time PCR in 478 patients
      with CHC (m/f: 314/164; mean age: 44.9 +/- 10.7; GT1: 387, GT4: 91) who completed
      treatment with peg-IFN-alpha-2a/ribavirin. All had a pretreatment liver biopsy.
      Steatosis and fibrosis were graded by board-certified pathologists according to
      Brunt and METAVIR respectively. RESULTS: The distribution of FDFT1 rs2645424 was
      GG: 186 (38.9%), AG: 222 (46.4%) and AA: 70 (14.6%) and of the rs738409 PNPLA3
      allele: CC: 269 (56.3%), CG: 177 (37.0%) and GG: 32 (6.7%). Overall, FDTF1
      polymorphism was not linked to the extent of steatosis or fibrosis. However, in
      patients without steatosis the AA genotype was associated with advanced fibrosis
      [AA: 8/20 (40.0%), AG: 6/70 (8.5%), GG: 9/57 (16.1%), P = 0.003]. In contrast,
      the minor PNPLA3 allele was associated with both steatosis and advanced fibrosis
      (P < 0.001). Both SNPs did not influence treatment response. CONCLUSION: The
      minor allele in FDFT1 was associated with advanced fibrosis in the non-steatotic
      but not in the steatotic subgroup. This may reflect different metabolic pathways
      in fibrosis progression for steatotic and non-steatotic patients with CHC.

PMID- 23870070
TI  - Determination of five flavonoids in different parts of Fordia cauliflora by ultra
      performance liquid chromatography/triple-quadrupole mass spectrometry and
      chemical comparison with the root of Millettia pulchra var. laxior.
AB  - BACKGROUND: The root of Fordia cauliflora Hemsl (FC) has long been used in
      southern China for the treatment of rheumatism, bruises, dementia in children,
      and valetudinarianism. However, sometimes it is mixed with other parts. And it
      has always been confused with the root of Millettia pulchra (Benth.) Kurz var.
      laxior (Dunn) Z. Wei (MP) by the local people. The chemical differences between
      the two ethnic drugs are not clear until now. The aim of this study is to develop
      a precise and accurate method to characterize and quantify multiple chemical
      components of FC, which is helpful for the quality evaluation and identification
      of FC. RESULTS: A method coupling ultra performance liquid chromatography (UPLC)
      with triple-quadrupole mass spectrometry (QqQ-MS) was first developed for
      simultaneous determination of five flavonoids in different parts of FC and the
      root of MP, based on a UPLC-diode array detection (DAD) fingerprint method. All
      calibration curves showed good linearity (R2>0.99) within test ranges. The
      overall LOD and LOQ were lower than 2.5 ng/mL and 5.0 ng/mL, respectively. The
      RSDs for intra- and inter-day of five analytes were less than 2.83% and 3.04%,
      respectively. Recovery studies for the quantified compounds were found to be
      within the range 93.6-99.8% with RSD less than 5.73%. The results suggest that
      the root, traditionally used medicinal part, yields the highest flavanoid content
      in FC. Pachycarin A, 3',4'-dimethoxy(2'',3'':7,8) furanoflavone, karanjachromene
      and isoderricin A can be used to differentiate between FC and MP samples.
      CONCLUSIONS: The present method is specific, precise and reliable, and is
      suitable for characterizing and quantifying multiple chemical components of FC.

PMID- 23870068
TI  - A systematic review of the relationships between social capital and socioeconomic
      inequalities in health: a contribution to understanding the psychosocial pathway
      of health inequalities.
AB  - INTRODUCTION: Recent research on health inequalities moves beyond illustrating
      the importance of psychosocial factors for health to a more in-depth study of the
      specific psychosocial pathways involved. Social capital is a concept that
      captures both a buffer function of the social environment on health, as well as
      potential negative effects arising from social inequality and exclusion. This
      systematic review assesses the current evidence, and identifies gaps in
      knowledge, on the associations and interactions between social capital and
      socioeconomic inequalities in health. METHODS: Through this systematic review we
      identified studies on the interactions between social capital and socioeconomic
      inequalities in health published before July 2012. RESULTS: The literature search
      resulted in 618 studies after removal of duplicates, of which 60 studies were
      eligible for analysis. Self-reported measures of health were most frequently
      used, together with different bonding, bridging and linking components of social
      capital. A large majority, 56 studies, confirmed a correlation between social
      capital and socioeconomic inequalities in health. Twelve studies reported that
      social capital might buffer negative health effects of low socioeconomic status
      and five studies concluded that social capital has a stronger positive effect on
      health for people with a lower socioeconomic status. CONCLUSIONS: There is
      evidence for both a buffer effect and a dependency effect of social capital on
      socioeconomic inequalities in health, although the studies that assess these
      interactions are limited in number. More evidence is needed, as identified
      hypotheses have implications for community action and for action on the
      structural causes of social inequalities.

PMID- 23870071
TI  - Cytosolic calcium, hydrogen peroxide and related gene expression and protein
      modulation in Arabidopsis thaliana cell cultures respond immediately to altered
      gravitation: parabolic flight data.
AB  - Callus cell cultures of Arabidopsis thaliana (cv. Columbia) were exposed to
      parabolic flights in order to assess molecular, short-term responses to altered
      gravity fields. Using transgenic cell lines, hydrogen peroxide (H2 O2 ) and
      cytosolic Ca(2+) were continuously monitored. In parallel, the metabolism of
      samples was chemically quenched (RNAlater, Ambion for RNA; acid/base for NADPH,
      NADP) at typical stages of a parabola [1 g before pull up; end of pull up (1.8
      g), end of microgravity (20 s) and end of pull out (1.8 g)]. Cells exhibited an
      increase in both Ca(2+) and H2 O2 with the onset of microgravity, and a decline
      thereafter. This behaviour was accompanied by a decrease of the NADPH/NADP redox
      ratio, indicating Ca(2+) -dependent activation of a NADPH oxidase. Microarray
      analyses revealed concomitant expression profiles. At the end of the microgravity
      phase, 396 transcripts were specifically up-, while 485 were down-regulated. Up
      regulation was dominated by Ca(2+) - and ROS-related gene products. The same
      material was also used for analysis of phosphopeptides with 2-D SDS PAGE.
      Relevant spots were identified by liquid chromatography-MS. With the exception of
      a chaperone (HSP 70-3), hypergravity (1.8 g) and microgravity modified different
      sets of proteins. These are partly involved in primary metabolism (glycolysis,
      gluconeogenesis, citrate cycle) and detoxification of ROS. Taken together, these
      data show that both gene expression and protein modulation jointly respond within
      seconds to alterations in the gravity field, with a focus on metabolic
      adaptation, signalling and control of ROS. 

PMID- 23870072
TI  - A schema using fixed anatomic landmarks for biopsy site identification on the
      head and neck.

PMID- 23870073
TI  - Temperature during the free-living phase of an ectoparasite influences the
      emergence pattern of the infective phase.
AB  - Understanding the population dynamics and co-evolution of host-parasite systems
      requires detailed knowledge of their phenology which, in turn, requires a deep
      knowledge of the effect of abiotic factors on the life cycles of organisms.
      Temperature is known to be a key environmental influence that participates in the
      regulation of diapause. Yet, not much is known about the effect of temperature on
      the free-living stages of true parasites and how it may influence host-parasite
      interactions. Here we experimentally study the effect of ambient temperature on
      overwintering pupae of Carnus hemapterus (Diptera, Carnidae), an ectoparasitic
      fly of various bird species. We also test whether chilling is a prerequisite for
      completion of diapause in this species. In the course of three winter seasons we
      experimentally exposed carnid pupae from nests of various host species to spring
      temperatures with and without chilling and recorded the emergence patterns in
      experimental and control groups. Experimental groups showed an advanced emergence
      date, a lower emergence rate and, consequently, a protracted emergence period.
      Chilling had no obvious effect on the start of emergence but it did advance the
      mean emergence date, shortened the length of the emergence period when compared
      with the control treatment and increased the emergence rate when compared with
      the spring treatment. This study identifies an environmental cue, namely
      temperature during the free-living stage, affecting the emergence of a widespread
      parasite and demonstrates the plasticity of diapause in this parasite. Our
      findings are of potential significance in understanding host-parasite
      interactions.

PMID- 23870074
TI  - The traditional practice of canine bud removal in the offspring of Ethiopian
      immigrants.
AB  - BACKGROUND: The custom of canine bud removal has detrimental consequences on
      children's general health and dental care. The objective of this study was to
      assess whether the prevalence of missing primary canines and dental defects in
      offspring of emigrants from Ethiopia is greater than in offspring of native
      Israeli parents of similar socioeconomic class. METHODS: 477 children of
      Ethiopian descent and 317 offspring of native Israeli parents, from 21 nursery
      schools and kindergartens, underwent dental examinations aimed to determine the
      presence or absence of primary canines and of developmental enamel defects on
      adjacent teeth to the primary canines. For purposes of analysis, children were
      classified into two age groups: younger (ages 18-48 months) and older (ages 49-82
      months). RESULTS: Canines were present in more Israeli than Ethiopian younger
      children, 87.5% vs. 42.3%, p=0.0001; and in more Israeli than Ethiopian older
      children, 92.6% vs. 40.4%, p=0.0001. More dental defects were detected in
      Ethiopian than in Israeli younger children, 32% vs. 3.9%, p=0.0001; and in more
      Ethiopian than Israeli older children, 31.2% vs. 5.8%, p=0.0001. CONCLUSIONS: The
      prevalence of missing primary canines and dental defects was greater among
      offspring of parents who had emigrated from Ethiopia 15-20 years earlier than
      among offspring of native Israeli parents living in the same low socioeconomic
      neighborhoods.

PMID- 23870075
TI  - Ongoing outbreak of hepatitis A in Italy: preliminary report as of 31 May 2013.

PMID- 23870076
TI  - Joint analysis by the Nordic countries of a hepatitis A outbreak, October 2012 to
      June 2013: frozen strawberries suspected.

PMID- 23870078
TI  - Distribution of Salmonella enterica isolates from human cases in Italy, 1980 to
      2011.

PMID- 23870077
TI  - Pet rat harbouring Seoul hantavirus in Sweden, June 2013.

PMID- 23870079
TI  - Pilot study to introduce a notification card for partner notification of sexually
      transmitted infections in Catalonia, Spain, June 2010 to June 2011.

PMID- 23870080
TI  - ECDC launches the second version of the EPIS-FWD platform.

PMID- 23870081
TI  - Repair of acute inferior wall myocardial infarction-related basal ventricular
      septal defect: transatrial versus transventricular approach.
AB  - BACKGROUND: We describe our contemporary experience for the management of
      patients with an acute postinfarction basal ventricle septal defect (VSD) using
      the transatrial (TA) and transventricular (TV) approaches. METHODS: Retrospective
      review of all patients diagnosed with an ischemic basal VSD since January 2000.
      There were 20 patients with a median age of 68 years (39 to 85); 13 (65%) were
      males. Median time from diagnosis of the ischemic basal VSD to operation was 22
      hours (6 to 144). RESULTS: All patients received standard patch closure of the
      septal defect with exposure of the VSD through the TA approach in eight patients
      (40%) and the TV approach in 12 (60%). All TA group patients received tricuspid
      valve replacement, while in the TV group, two had tricuspid valve replacement and
      two repair. Five patients (25%) had clinically insignificant (<0.5 mm) residual
      septal defects; three additional patients (15%) experienced patch dehiscence and
      two (10%) underwent re-exploration. There were five mortalities (25%): one in the
      TA group (right ventricular heart failure) and four in the TV group (one right
      ventricular heart failure, three ventriculotomy site hemorrhage or patch
      dehiscence). Preoperative right atrial pressure (p=0.0003) and right ventricular
      dysfunction (p=0.04) were predictors of hospital mortality. Follow-up of the
      hospital survivors was 4.3 years (40 days to 11.5 years) with one death at seven
      years. CONCLUSION: Operative mortality associated with repair of postinfarction
      basal ventricular septal defect is high and is related to right ventricular
      failure and bleeding from the ventriculotomy. The TA approach avoids
      ventriculotomy-associated bleeding and provides excellent exposure but is
      associated with an increased incidence of tricuspid valve replacement.

PMID- 23870082
TI  - Nephroprotective and curative effects of Ficus religiosa latex extract against
      cisplatin-induced acute renal failure.
AB  - CONTEXT: Ficus religiosa L. (Moraceae) is widely planted in the tropics. Its
      chemical constituents include tannin, saponin gluanol acetate, beta-sitosterol,
      leucoanthocyanidin and leucoanthocyanin which are used for the treatment of pain,
      inflammation, impotence, menstrual disturbances, uterine tonic and urine related
      problems. OBJECTIVE: To determine the possible nephroprotective and curative
      effects of F. religiosa latex methanol extract against cisplatin induced acute
      renal failure. MATERIALS AND METHODS: Methanol extract was obtained by maceration
      process. Rats were divided in five groups. Group 1 was administered acacia (2%
      w/v) of 5 ml/kg throughout the experiment; group 2 was treated with single dose
      of cisplatin (5 mg/kg i.p.) on the 1st day; group 3 (200 mg/kg p.o.) of extract
      control for the 1st to 10th day, group 4 (200 mg/kg p.o.) of extract from the 1st
      to 10th day and a single dose of cisplatin (5 mg/kg, i.p.) on 11th day while
      group 5 received the same dose of cisplatin on day 1 and extract (200 mg/kg p.o.)
      from the 7th to 16th day. RESULTS: Phytochemical screening of the extract
      revealed the presence of glycoside, alkaloids, tannins (phenolic compounds),
      flavonoids and amino acids. The half maximal inhibitory concentration (IC50)
      values of the extract were 31.75 +/- 0.12 and 18.35 +/- 0.48 ug/ml, respectively.
      The cisplatin-treated group 2 showed significant changes; renal functions,
      biochemical parameters and histopathology were significantly (**p < 0.01)
      recovered by 200 mg/kg curative and protective groups. DISCUSSION AND CONCLUSION:
      These findings demonstrated that F. religiosa latex and constituents have
      excellent nephroprotective and curative activities and thus have great potential
      as a source for natural health products.

PMID- 23870084
TI  - Methylation differences of the neuronatin gene promoter region in liver between
      normal and cloned pigs.
AB  - Abnormal phenotypes in cloned pigs can be partly due to changes in epigenetic
      modifications such as methylation levels of promoter CpG islands. Neuronatin is
      an imprinted gene, conserved in human, pig, cattle and mouse, which is expressed
      exclusively from the paternal allele. Three CpG islands located in the promoter
      region of the porcine neuronatin gene have the potential to regulate the gene
      expression by cytosine methylation. To illustrate whether neuronatin was
      differentially expressed among nuclear transfer macroglossia-positive and nuclear
      transfer macroglossia-negative pigs and in vitro-fertilized pigs, we detected its
      expression level by qRT-PCR and further quantified methylation levels by
      pyrosequencing DNA from the liver. The results showed that neuronatin was
      expressed at a significantly higher level in livers of nuclear transfer
      macroglossia-positive pigs compared with normal cloned and in vitro-fertilized
      pigs. Livers of nuclear transfer macroglossia-positive pigs also had a
      significantly lower methylation level at CpG island 2 and CpG island 3 in the
      promoter region. 

PMID- 23870083
TI  - Erythrocyte folate status and serum iron levels in patients undergoing
      hemodialysis.
AB  - The present study was aimed to evaluate erythrocyte folate and the iron levels in
      diabetes and hypertension patients treated with/without hemodialysis. The effects
      of erythropoietin and iron treatment as well as vitamin supplementation on
      measured parameters were considered. The 67 controls consisted of healthy
      subjects (n = 22), hypertensive subjects (n = 22), and diabetic subjects (n = 23)
      without any renal disorder. According to primary renal disorders, the patients
      undergoing hemodialysis (n = 68) were classified into four groups as diabetic
      nephropathy, hypertensive nephropathy, reflux nephropathy or interstitial
      nephritis, and renal insufficiency depending on other causative factors. The mean
      value of erythrocyte folate levels of all patients undergoing hemodialysis was
      higher than the healthy control group (P < 0.05). Erythrocyte folate levels in
      hypertensive and diabetic nephropathy patients were higher than their own
      hypertensive or diabetic controls and also healthy controls (both, P < 0.05).
      Serum iron levels of all subgroups in hemodialysis patients were found to be
      similar with healthy controls (all, P > 0.05). The only significance observed
      within the subgroups was between diabetic controls and diabetic nephropathy
      patients (P < 0.05). None of the treatment or supplementation of erythropoietin,
      iron and vitamin affected erythrocyte folate levels (all, P > 0.05). The increase
      in erythrocyte folate status of patients with end stage renal diseases might be
      the result of sum or individual effects of causative factors such as renal
      pathology, compensation mechanism against renal anemia, or routine folate
      supplementation. 

PMID- 23870085
TI  - Administration of chemotherapy with palliative intent in the last 30 days of
      life: the balance between palliation and chemotherapy.
AB  - BACKGROUND: Appropriately timed cessation of chemotherapy is an important aspect
      of good quality palliative care. There is wide variation in the reported rates of
      chemotherapy administration within the last 30 days of life. AIMS: To identify
      predictors of death within 30 days of receiving palliative chemotherapy, and to
      propose a standard definition by which oncologists and cancer centres can be
      compared. METHODS: Patients who received palliative chemotherapy at a regional
      cancer centre and its rural outreach unit between 2009 and 2011 were included. An
      adjusted logistic regression model, including all variables, was fit to identify
      predictors of death within 30 days of receiving palliative chemotherapy. RESULTS:
      Over a 3-year period, 1131 patients received palliative chemotherapy, 138 (12%)
      died within 30 days of receiving palliative chemotherapy. Predictors of death
      within 30 days of palliative chemotherapy were: less than 30 days contact with
      palliative care (odds ratio 3.30 (95% confidence interval 2.04-5.34), P < 0.001)
      and male gender (odds ratio 2.02 (95% confidence interval 1.24-3.31), P =
      0.0049), but treating clinician, tumour chemoresponsiveness, age, body mass index
      and survival from initial diagnosis were not. CONCLUSION: Patients who received
      chemotherapy in the last 30 days of life were more likely to be male and have a
      shorter duration of palliative care team involvement. In this study, the observed
      rate of death within 30 days of chemotherapy is within the range of published
      data. It is recommended that a standard definition be used to benchmark medical
      oncology centres and individual oncologists, and to allow comparison over time.

PMID- 23870086
TI  - Association of RSV-related hospitalization and non-compliance with palivizumab
      among commercially insured infants: a retrospective claims analysis.
AB  - BACKGROUND: Palivizumab has been shown to decrease the incidence of
      hospitalization due to respiratory syncytial virus (RSV) in infants at risk of
      severe RSV disease. We examined the association between compliance with
      palivizumab dosing throughout the RSV season and risk of RSV-related
      hospitalization in clinical practice. METHODS: Subjects who were born and
      discharged from the hospital before the RSV season and received >=1 palivizumab
      dose during their first RSV season were identified from a large US commercial
      health insurance database between 01/01/03 and 12/31/09. Subjects were deemed
      compliant if they received >=5 palivizumab doses without gaps (>35 days) and
      their first dose was received by November 30. RSV-related hospitalizations were
      identified using ICD-9-CM diagnosis codes and examined over 2 observation
      periods: post-index dose and RSV season. A Cox proportional hazard model was used
      to evaluate the association between non-compliance and RSV-related
      hospitalization. RESULTS: Of the 5,003 subjects who received palivizumab, 62%
      were deemed non-compliant. Non-compliant subjects had significantly higher
      unadjusted rates of RSV-related hospitalizations compared to compliant subjects
      during both observation periods (post-index: 6.1 vs. 2.8 per 100 infant seasons,
      p < 0.001; RSV season: 5.9% vs. 2.3%; p < 0.001). In multivariate analyses, non
      compliance was significantly associated with higher risk of RSV-related
      hospitalization (HR = 2.01; p < 0.001). Of the 225 RSV-related hospitalizations
      observed during the RSV season, 61 (27%) occurred before the first dose of
      palivizumab. CONCLUSIONS: Subjects who did not receive monthly dosing of
      palivizumab throughout the RSV season had significantly higher rates of RSV
      related hospitalizations. The RSV-related hospitalizations prior to the first
      dose of palivizumab suggest some dosing was started too late.

PMID- 23870087
TI  - Associations between mortality and meteorological and pollutant variables during
      the cool season in two Asian cities with sub-tropical climates: Hong Kong and
      Taipei.
AB  - BACKGROUND: Numerous studies have found associations between extreme temperatures
      and human mortality but relatively few studies have been done in sub-tropical and
      tropical cities, especially in Asia. In this study we examine the impact of cold
      temperatures, cold waves and other meteorological and environmental variables on
      cool season mortality in 2 subtropical Asian cities. METHODS: Separate analysis
      of daily mortality time-series from Hong Kong and Taipei using Generalized
      Additive Models with natural mortality as the outcome daily mean temperature as
      the main explanatory variable and relative humidity, solar radiation, wind speed,
      pollutants (nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), respirable
      suspended particulates (PM(10)), ozone (O(3)), seasonality and day of the week
      controlled as potential confounders. Lags up to 35 days were considered for
      temperature, and distributed lag models were used to determine the number of lags
      for final models. Subgroup analyses were also done by gender, age group, cause of
      death and geographical area of residence. RESULTS: Cold temperatures were
      strongly associated with higher mortality with lagged effects persisting up to 3
      weeks in Hong Kong and 2 weeks in Taipei. Cold effects were much stronger for
      deaths among older people and non-cancer deaths. Prolonged cold spells modestly
      but significantly raised mortality after accounting for the effects of individual
      cold days. Higher daily ozone levels were also strongly associated with higher
      short-term mortality in Taipei and Hong Kong, while relative humidity and solar
      radiation were weakly and inconsistently associated with mortality. CONCLUSIONS:
      Cold temperatures and cold spells substantially increase short-term mortality in
      sub-tropical Asian cities particularly among the elderly. Greater attention needs
      to be paid to the adverse health effects of cold temperatures. Interventions
      including provisions of shelters, cold weather warnings and education about the
      possible health effects of cold temperature should be carried out in sub-tropical
      areas.

PMID- 23870088
TI  - Identification of the lamin A/C phosphoepitope recognized by the antibody P-STM
      in mitotic HeLa S3 cells.
AB  - BACKGROUND: Lamins A and C, two major structural components of the nuclear lamina
      that determine nuclear shape and size, are phosphoproteins. Phosphorylation of
      lamin A/C is cell cycle-dependent and is involved in regulating the assembly
      disassembly of lamin filaments during mitosis. We previously reported that P-STM,
      a phosphoepitope-specific antibody raised against the autophosphorylation site of
      p21-activated kinase 2, recognizes a number of phosphoproteins, including lamins
      A and C, in mitotic HeLa cells. RESULTS: Here, using recombinant proteins and
      synthetic phosphopeptides containing potential lamin A/C phosphorylation sites in
      conjunction with in vitro phosphorylation assays, we determined the lamin A/C
      phosphoepitope(s) recognized by P-STM. We found that phosphorylation of Thr-19 is
      required for generating the P-STM phosphoepitope in lamin A/C and showed that it
      could be created in vitro by p34cdc2/cyclin B kinase (CDK1)-catalyzed
      phosphorylation of lamin A/C immunoprecipitated from unsynchronized HeLa S3
      cells. To further explore changes in lamin A/C phosphorylation in living cells,
      we precisely quantified the phosphorylation levels of Thr-19 and other sites in
      lamin A/C isolated from HeLa S3 cells at interphase and mitosis using the SILAC
      method and liquid chromatography-tandem mass spectrometry. The results showed
      that the levels of phosphorylated Thr-19, Ser-22 and Ser-392 in both lamins A and
      C, and Ser-636 in lamin A only, increased -2- to 6-fold in mitotic HeLa S3 cells.
      CONCLUSIONS: Collectively, our results demonstrate that P-STM is a useful tool
      for detecting Thr-19-phosphorylated lamin A/C in cells and reveal quantitative
      changes in the phosphorylation status of major lamin A/C phosphorylation sites
      during mitosis.

PMID- 23870089
TI  - HLA class III genes involvement in Kawasaki disease: a case-control study in
      Caucasian population.
AB  - Kawasaki disease (KD) is an acute, multisystemic, febrile vasculitis of unknown
      aetiology, which affects young children mainly under 5 years of age. The clinical
      variability has until now prevented to decrypt KD aetiological factors. Recently,
      the importance of genetics and the pivotal role of the immune system have
      emerged. To investigate in this direction, genomic DNA from 74 Caucasian KD cases
      and 440 healthy controls has been analysed to characterize functional
      polymorphisms of relevant HLA class III genes: AGER -429 and -374, TNF -857, -308
      and -238, HSPA1A +190, HSPA1B +1267 and HSPA1L +2437. Allele, genotype and
      haplotype frequencies were therefore compared with the chi-squared test and
      Fisher's exact test. Our data showed significant deviations between patients with
      Kawasaki disease and controls concerning the TNF -308 polymorphism genotype (GG:
      P = 0.0449) and allele (G,A: P = 0.0433) and -238 polymorphism genotype
      frequencies (AA: P = 0.0351). Moreover, we found differences concerning the
      HSPA1A +190 polymorphism (GC: P = 0.0317) and the HSPA1L +2437 polymorphism (TT:
      P = 0.0072; TC: P = 0.0250; T: P = 0.0037; C: P = 0.0037). The calculation of TNF
      -238 and HSPA1L haplotype frequencies also pointed out a statistically
      significant decrease in patients of CG haplotype (P = 0.0001), which could have a
      role in protecting from the inflammatory processes that characterize the disease
      progression. The results obtained point to a possible involvement of the entire
      HLA class III region in KD susceptibility. 

PMID- 23870090
TI  - Proteomic analysis of purified protein derivative of Mycobacterium tuberculosis.
AB  - BACKGROUND: Purified protein derivative (PPD) has been used for more than half a
      century as an antigen for the diagnosis of tuberculosis infection based on
      delayed type hypersensitivity. Although designated as "purified," in reality, the
      composition of PPD is highly complex and remains ill-defined. In this report,
      high resolution mass spectrometry was applied to understand the complexity of its
      constituent components. A comparative proteomic analysis of various PPD
      preparations and their functional characterization is likely to help in short
      listing the relevant antigens required to prepare a less complex and more potent
      reagent for diagnostic purposes. RESULTS: Proteomic analysis of Connaught
      Tuberculin 68 (PPD-CT68), a tuberculin preparation generated from M.
      tuberculosis, was carried out in this study. PPD-CT68 is the protein component of
      a commercially available tuberculin preparation, Tubersol, which is used for
      tuberculin skin testing. Using a high resolution LTQ-Orbitrap Velos mass
      spectrometer, we identified 265 different proteins. The identified proteins were
      compared with those identified from PPD M. bovis, PPD M. avium and PPD-S2 from
      previous mass spectrometry-based studies. In all, 142 proteins were found to be
      shared between PPD-CT68 and PPD-S2 preparations. Out of the 354 proteins from M.
      tuberculosis-derived PPDs (i.e. proteins in either PPD-CT68 or PPD-S2), 37
      proteins were found to be shared with M. avium PPD and 80 were shared with M.
      bovis PPD. Alignment of PPD-CT68 proteins with proteins encoded by 24 lung
      infecting bacteria revealed a number of similar proteins (206 bacterial proteins
      shared epitopes with 47 PPD-CT68 proteins), which could potentially be involved
      in causing cross-reactivity. The data have been deposited to the ProteomeXchange
      with identifier PXD000377. CONCLUSIONS: Proteomic and bioinformatics analysis of
      different PPD preparations revealed commonly and differentially represented
      proteins. This information could help in delineating the relevant antigens
      represented in various PPDs, which could further lead to development of a lesser
      complex and better defined skin test antigen with a higher specificity and
      sensitivity.

PMID- 23870091
TI  - Outcomes of endoscopic pyloric stenting in malignant gastric outlet obstruction:
      a retrospective study.
AB  - BACKGROUND: Up to 30% of patients with pancreatic cancer and more than 50% of
      patients with gastric cancer already have incurable disease, with distressing
      symptoms of gastric outlet obstruction at the time of presentation which require
      effective palliation. We decided to test the clinical outcomes of endoscopic
      stent placement in malignant gastric outlet obstruction. METHODS: In a
      retrospective single institution-based study, the charts of patients who had self
      expandable metal stents placed to alleviate malignant gastric outlet obstruction
      were reviewed. Charts were reviewed to assess improvement in oral intake
      according to the Gastric Outlet Obstruction Scoring System (GOOSS), and in order
      to also evaluate technical success and complications of the procedure. RESULTS:
      69 patients with successful stent placement were retrospectively evaluated.
      Within 7 and 28 days after stent placement respectively, 85.5% and 80% benefited
      from stent insertion, with an increase in the GOOSS score of > 1. Resumption of
      soft or low residue diet (GOOSS 2-3) was achieved in 53.6% at day 7 and in 62% of
      patients at day 28, respectively. Of the patients achieving a GOOSS score of 2-3,
      17.3% remained on a soft or low residue diet at 24 weeks or at last follow up,
      while 46% died. Stent related adverse events occurred in 10 patients (14%),
      including stent blockade in 7 and stent migration in 3 patients. CONCLUSION:
      Endoscopic enteral stenting promptly increases oral intake in the majority of
      patients with malignant gastric outlet obstruction and is a safe procedure with a
      low rate of serious complications.

PMID- 23870092
TI  - A method to identify new molecular markers for assessing minimal residual disease
      in acute leukemia patients.
AB  - Acute leukemias (AL) comprise a heterogeneous group of hematologic malignancies,
      and individual patient responses to treatment can be difficult to predict.
      Monitoring of minimal residual disease (MRD) is thus very important and holds
      great potential for improving treatment strategies. Common MRD targets include
      recurrent cytogenetic abnormalities and mutations in important hematological
      genes; unfortunately well-characterized targets are lacking in many AL patients.
      Here we demonstrate a technical approach for the identification and mapping of
      novel clone-specific chromosomal abnormalities down to the nucleotide level. We
      used molecular cytogenetics, chromosome microdissection, amplification of the
      microdissected material, and next-generation sequencing to develop PCR-based MRD
      assays based on unique breakpoint sequences. 

PMID- 23870094
TI  - Control of recent community-based outbreaks of invasive meningococcal disease in
      men who have sex with men in Europe and the United States.

PMID- 23870093
TI  - Prenatal and early childhood bisphenol A concentrations and behavior in school
      aged children.
AB  - INTRODUCTION: Early life exposure to bisphenol A (BPA), an endocrine disrupting
      chemical used in some food and beverage containers, receipts, and dental
      sealants, has been associated with anxiety and hyperactivity in animal studies. A
      few human studies also show prenatal and childhood BPA exposure to be associated
      with behavior problems in children. METHODS: We measured BPA in urine from
      mothers during pregnancy and children at 5 years of age (N=292). Child behavior
      was assessed by mother and teacher report at age 7 years and direct assessment at
      age 9 years. RESULTS: Prenatal urinary BPA concentrations were associated with
      increased internalizing problems in boys, including anxiety and depression, at
      age 7. No associations were seen with prenatal BPA concentrations and behaviors
      in girls. Childhood urinary BPA concentrations were associated with increased
      externalizing behaviors, including conduct problems, in girls at age 7 and
      increased internalizing behaviors and inattention and hyperactivity behaviors in
      boys and girls at age 7. CONCLUSIONS: This study adds to the existing literature
      showing associations of early life BPA exposure with behavior problems, including
      anxiety, depression, and hyperactivity in children. Additional information about
      timing of exposure and sex differences in effect is still needed.

PMID- 23870095
TI  - A cluster of invasive meningococcal disease in young men who have sex with men in
      Berlin, October 2012 to May 2013.
AB  - Between October 2012 and May 2013, five cases of invasive meningococcal disease
      in young men who have sex with men (MSM) living in Berlin were notified to local
      health authorities in Germany. Three of the five cases died. All were caused by
      serogroup C variants with the finetype P1.5-1,10-8:F3-6. Awareness was increased
      through the use of community networks; an extension of the existing vaccination
      recommendation to all MSM is currently being considered.

PMID- 23870096
TI  - Carbapenemase-producing Enterobacteriaceae in Europe: a survey among national
      experts from 39 countries, February 2013.
AB  - The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to
      healthcare delivery, although its extent differs substantially from country to
      country. In February 2013, national experts from 39 European countries were
      invited to self-assess the current epidemiological situation of CPE in their
      country. Information about national management of CPE was also reported. The
      results highlight the urgent need for a coordinated European effort on early
      diagnosis, active surveillance, and guidance on infection control measures.

PMID- 23870097
TI  - Prevalence of human immunodeficiency virus and hepatitis C virus among French
      prison inmates in 2010: a challenge for public health policy.
AB  - We evaluated prevalence of human immunodeficiency virus (HIV) and hepatitis C
      virus (HCV) among prison inmates in France in 2010, in a cross-sectional single
      day study based on a two-stage design. Sampling favoured larger establishments
      and included all types of prisons. Establishments were stratified by geographical
      region. Estimates were adjusted by post-stratification of the total population of
      inmates in France. From 60,975 inmates in all 188 prisons on the sampling day,
      2,154 were selected from 27 prisons, and 1,876 questionnaires completed. HIV
      prevalence was estimated at 2.0% (95% confidence interval (CI): 0.9-4.2), 2.6%
      (95% CI: 0.7-8.8) in women and 2.0% (95% CI: 0.9-4.3) in men; 75% of inmates were
      receiving treatment for HIV. HCV prevalence was estimated at 4.8% (95% CI: 3.5
      6.5) and was higher for women (11.8%; 95% CI: 8.5-16.1) than men (4.5%; 95% CI:
      3.3-6.3). Almost half of HCV-infected inmates had chronic hepatitis C and 44%
      were receiving or had received treatment. HIV and HCV prevalence was six times
      higher than in the general population, and 2.5% of inmates had viraemic hepatitis
      C. The moment of incarceration provides an ideal opportunity for testing and
      treating, limiting spread of HCV and improving patients' prognosis.

PMID- 23870098
TI  - Prevalence of Coxiella burnetii in women exposed to livestock animals, Denmark,
      1996 to 2002.
AB  - Q fever is a zoonotic infection which can pose a danger to pregnant women. To our
      knowledge, Denmark has never experienced a clinically verified Q fever outbreak.
      We aimed to quantify risk of infection in pregnant women occupationally and
      environmentally exposed to Coxiella burnetii. The Danish National Birth Cohort
      collected blood samples from 100,418 pregnant women in the period 1996 to 2002.
      We sampled 195 women with occupational exposure to livestock (veterinarians and
      female farmers), 202 women with domestic exposure (dairy cattle and/or sheep) and
      a random sample of 459 unexposed women. Samples were screened for antibodies
      against C. burnetii by commercial enzyme-linked immunosorbent assay. Positive
      samples were confirmed by immunofluorescence (cut-off titre >=1:128). The
      proportion of seropositive women was higher in the occupationally exposed (47.2%
      seropositive; relative risk (RR): 9.8; 95% confidence interval (CI): 6.4-15.2)
      and the domestically exposed population (32.2% seropositive; RR: 6.7; 95% CI: 4.3
      10.6) than in unexposed women (4.8% seropositive). We found a high prevalence of
      antibodies to C. burnetii among pregnant women with occupational or domestic
      exposure to cattle and/or sheep compared with unexposed pregnant women. Our
      findings suggest that contact to livestock is a risk factor for C. burnetii
      infection in Denmark.

PMID- 23870099
TI  - International comparisons of health system performance among OECD countries:
      opportunities and data privacy protection challenges.
AB  - OBJECTIVE: Health data constitute a significant resource in most OECD countries
      that could be used to improve health system performance. Well-intended policies
      to allay concerns about breaches of confidentiality and to reduce potential
      misuse of personal health information may be limiting data use. A survey of 20
      OECD countries explored the extent to which countries have developed and use
      personal health data and the reasons why data use may be problematic in some.
      RESULTS: Countries are divided, with one-half engaged regularly in national data
      linkage studies to monitor health care quality. Country variation is linked to
      risk management in granting an exemption to patient consent requirements; in
      sharing identifiable data among government authorities; and in project approvals
      and granting access to data. The resources required to comply with data
      protection requirements is a secondary problem. The sharing of person-level data
      across borders for international comparisons is rarely reported and there were
      few examples of studies of health system performance. DISCUSSION: Laws and
      policies enabling data sharing and data linkage are needed to strengthen national
      information infrastructure. To develop international studies comparing health
      care quality and health system performance, actions are needed to address
      heterogeneity in data protection practices.

PMID- 23870100
TI  - Contrasting tensions between patients and PCPs in chronic pain management: a
      qualitative study.
AB  - OBJECTIVE: With greater scrutiny on primary care providers' (PCPs) approaches to
      chronic pain management, more research is needed to clarify how concerns and
      uncertainties about opioid therapy affect the ways both patients with chronic
      pain and PCPs experience primary care interactions. The goal of this qualitative
      study was to develop a better understanding of the respective experiences,
      perceptions, and challenges that patients with chronic pain and PCPs face
      communicating with each other about pain management. DESIGN: Purposive and
      snowball sampling techniques were used to identify 14 PCPs. Patients who received
      >=6 opioid prescriptions during the prior year were selected at random from the
      panels of participating physicians. Face-to-face in-depth interviews were
      conducted individually with patients and PCPs. SETTING: VISN 11 Roudebush VA
      Medical Center (RVAMC) in Indianapolis, Indiana. SUBJECTS: Fourteen PCPs and 26
      patients with chronic pain participated. METHODS: An inductive thematic analysis
      was conducted separately with patient and PCP interview data, after which the
      emergent themes for both groups were compared and contrasted. RESULTS: Three
      notable tensions between patients and PCPs were discovered: 1) the role of
      discussing pain versus other primary care concerns, 2) acknowledgment of pain and
      the search for objective evidence, and 3) recognition of patient individuality
      and consideration of relationship history. CONCLUSIONS: Competing demands of
      primary care practice, differing beliefs about pain, and uncertainties about the
      appropriate place of opioid therapy in chronic pain management likely contributed
      to the identified tensions. Several clinical communication strategies to help
      PCPs mitigate and manage pain-related tensions are discussed.

PMID- 23870101
TI  - Family members' perceptions of end-of-life care across diverse locations of care.
AB  - BACKGROUND: The goal of the study was to assess perceived level of satisfaction
      with end-of-life care, focusing on the last 48 hours of life. METHODS: A
      previously validated instrument was used in a telephone survey with bereaved
      family members (n=90) of patients who died within an organization in British
      Columbia. RESULTS: Bereaved family members had many unmet needs for information
      about the patient's changing condition, the process of dying, how symptoms would
      be managed and what to do at the time of death. In addition, many bereaved
      relatives felt that the patient or resident had an unmet need for emotional
      support and that their own emotional needs were not addressed adequately. The
      last place of care had the most significant effect on all of these variables,
      with acute care and residential care having the most unmet needs. Hospice had the
      fewest unmet needs, followed by the palliative and the intensive care units.
      CONCLUSIONS: We discuss these findings in relation to overall satisfaction with
      care, focus on individual, ethno-cultural and diversity issues, information and
      decision-making, symptom management and attending to the family. We conclude by
      offering possible practices address the end-of-life needs of patients and family
      members.

PMID- 23870102
TI  - Meningioma patients diagnosed 2007-2009 and the association with use of mobile
      and cordless phones: a case-control study.
AB  - BACKGROUND: To study the association between use of wireless phones and
      meningioma. METHODS: We performed a case-control study on brain tumour cases of
      both genders aged 18-75 years and diagnosed during 2007-2009. One population
      based control matched on gender and age was used to each case. Here we report on
      meningioma cases including all available controls. Exposures were assessed by a
      questionnaire. Unconditional logistic regression analysis was performed. RESULTS:
      In total 709 meningioma cases and 1,368 control subjects answered the
      questionnaire. Mobile phone use in total produced odds ratio (OR) = 1.0, 95%
      confidence interval (CI) = 0.7-1.4 and cordless phone use gave OR = 1.1, 95% CI =
      0.8-1.5. The risk increased statistically significant per 100 h of cumulative use
      and highest OR was found in the fourth quartile (>2,376 hours) of cumulative use
      for all studied phone types. There was no statistically significant increased
      risk for ipsilateral mobile or cordless phone use, for meningioma in the temporal
      lobe or per year of latency. Tumour volume was not related to latency or
      cumulative use in hours of wireless phones. CONCLUSIONS: No conclusive evidence
      of an association between use of mobile and cordless phones and meningioma was
      found. An indication of increased risk was seen in the group with highest
      cumulative use but was not supported by statistically significant increasing risk
      with latency. Results for even longer latency periods of wireless phone use than
      in this study are desirable.

PMID- 23870103
TI  - Lymphatic filariasis control in Tanzania: effect of six rounds of mass drug
      administration with ivermectin and albendazole on infection and transmission.
AB  - BACKGROUND: Control of lymphatic filariasis (LF) in most countries of sub-Saharan
      Africa is based on annual mass drug administration (MDA) with a combination of
      ivermectin and albendazole, in order to interrupt transmission. We present
      findings from a detailed study on the effect of six rounds of MDA with this drug
      combination as implemented by the National Lymphatic Filariasis Elimination
      Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.
      METHODS: The effect of treatment on transmission and human infection was
      monitored in a community- and a school-based study during an 8-year period (one
      pre-intervention and 7 post-intervention years) from 2003 to 2011. RESULTS:
      Before intervention, 24.5% of the community population had microfilariae (mf) in
      the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific
      antibodies to the recombinant filarial antigen Bm14. One year after the sixth
      MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%,
      respectively. During the same period, the CFA prevalence among new intakes of
      Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line
      with this, transmission by the three vectors (Anopheles gambiae, An. funestus and
      Culex quinquefasciatus) as determined by dissection declined sharply (overall
      vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2%
      between pre-intervention and fifth post-intervention period). A major shift in
      vector species composition, from predominantly anopheline to almost exclusively
      culicine was observed over the years. This may be largely unrelated to the MDAs
      but may have important implications for the epidemiology of LF in the area.
      CONCLUSIONS: Six MDAs caused considerable decrease in all the measured indices
      for transmission and human infection. In spite of this, indices were still
      relatively high in the late period of the study, and it may take a long time to
      reach the recommended cut-off levels for interruption of transmission unless
      extra efforts are made. These should include increased engagement of the target
      population in the control activities, to ensure higher treatment coverage. It is
      expected that the recent initiative to distribute insecticide impregnated bed
      nets to every household in the area will also contribute towards reaching the
      goal of successful LF elimination.

PMID- 23870104
TI  - Neonatal acute myocardial infarction of unknown etiology treated with surgical
      thrombectomy.
AB  - Coronary artery thrombosis and resultant myocardial infarction in neonates are
      exceedingly rare. Seldom does a neonate survive this myocardial insult. Often
      there is an underlying predisposition to coronary artery thrombosis, such as
      thrombophilia, central line placement, or myocarditis. Treatment attempts have
      consisted of thrombolysis and supportive care. We present a case of acute left
      main coronary artery (LMCA) thrombosis of unknown etiology in a neonate, without
      ventricular dilatation. Flow into the LMCA was suggested echocardiographically,
      but a high clinical suspicion led to urgent cardiac catheterization. Once
      complete occlusion of the LMCA was demonstrated angiographically, emergent
      surgical thrombectomy was performed, which has never previously been reported. 

PMID- 23870105
TI  - Molecular evolution in court: analysis of a large hepatitis C virus outbreak from
      an evolving source.
AB  - BACKGROUND: Molecular phylogenetic analyses are used increasingly in the
      epidemiological investigation of outbreaks and transmission cases involving
      rapidly evolving RNA viruses. Here, we present the results of such an analysis
      that contributed to the conviction of an anesthetist as being responsible for the
      infection of 275 of his patients with hepatitis C virus. RESULTS: We obtained
      sequences of the NS5B and E1-E2 regions in the viral genome for 322 patients
      suspected to have been infected by the doctor, and for 44 local, unrelated
      controls. The analysis of 4,184 cloned sequences of the E1-E2 region allowed us
      to exclude 47 patients from the outbreak. A subset of patients had known dates of
      infection. We used these data to calibrate a relaxed molecular clock and to
      determine a rough estimate of the time of infection for each patient. A similar
      analysis led to an estimate for the time of infection of the source. The date
      turned out to be 10 years before the detection of the outbreak. The number of
      patients infected was small at first, but it increased substantially in the
      months before the detection of the outbreak. CONCLUSIONS: We have developed a
      procedure to integrate molecular phylogenetic reconstructions of rapidly evolving
      viral populations into a forensic setting adequate for molecular epidemiological
      analysis of outbreaks and transmission events. We applied this procedure to a
      large outbreak of hepatitis C virus caused by a single source and the results
      obtained played a key role in the trial that led to the conviction of the
      suspected source.

PMID- 23870106
TI  - Orthogonal analytical methods for botanical standardization: determination of
      green tea catechins by qNMR and LC-MS/MS.
AB  - The development of analytical methods for parallel characterization of multiple
      phytoconstituents is essential to advance the quality control of herbal products.
      While chemical standardization is commonly carried out by targeted analysis using
      gas or liquid chromatography-based methods, more universal approaches based on
      quantitative (1)H NMR (qHNMR) measurements are being used increasingly in the
      multi-targeted assessment of these complex mixtures. The present study describes
      the development of a 1D qHNMR-based method for simultaneous identification and
      quantification of green tea constituents. This approach utilizes computer
      assisted (1)H iterative Full Spin Analysis (HiFSA) and enables rapid profiling of
      seven catechins in commercial green tea extracts. The qHNMR results were cross
      validated against quantitative profiles obtained with an orthogonal LC-MS/MS
      method. The relative strengths and weaknesses of both approaches are discussed,
      with special emphasis on the role of identical reference standards in qualitative
      and quantitative analyses.

PMID- 23870107
TI  - Determination of bile salt critical micellization concentration on the road to
      drug discovery.
AB  - With the discovery of the bile acid (BA)-activated nuclear and membrane
      receptors, the role of BAs as signalling molecules in important paracrine and
      endocrine networks has been fully documented in the last decade. Besides
      regulating their own synthesis and transport, BAs have been demonstrated being
      involved in triggering the adaptive response to cholestasis and other insults to
      liver. More to the point, their recognized ability to control the general energy
      related metabolism and inflammation processes has contributed to justify the
      renewed interest towards this class of amphiphilic steroidal compounds. All these
      evidences feed a continuing interest in the BA research aimed at designing and
      synthesizing new side chain- and body-modified derivatives endowed with improved
      biological and physico-chemical profiles, as well as with proper ADMET behaviour.
      In this context, the micellar aggregation of BAs, and the respective critical
      micellization concentration (CMC) value (determined on the BA sodium salt, BS),
      is considered a key parameter that needs to be determined in the preliminary
      phase of compound characterization, being implicated in cytotoxicity issues. An
      extraordinary variety of different analytical techniques and methods have been
      proposed along the years with the aim of better identifying the start of the self
      aggregation process of BS monomers. The unicity of the physico-chemical nature of
      such class of compounds can be invoked to explain this unusual interest.
      Accordingly, a number of both invasive and non-invasive approaches have been
      developed along with a limited number of indirect chromatographic-based
      estimation strategies. Worth to be mentioned among the non-invasive determination
      methods are those based on potentiometry, freezing point depression, surface
      tension, nuclear magnetic resonance, viscosimetry, turbidimetry,
      microcalorimetry, refractometry, conductimetry, spectrophotometry, cholesterol
      solubilization, and monoglucuronide solubilization. Dye solubilization- and
      fluorescence-based methods deserve instead credit among the invasive
      methodological approaches. Indirect chromatographic methods based on capillary
      electrophoresis and high performance liquid chromatography analysis also
      demonstrated to be profitably exploited for the CMC estimation, especially when a
      small amount of sample is available. The collection of literature data reveals
      that the CMC value of a given BS is markedly related to the method selected for
      determining it as well as to the experimental conditions applied during the
      analysis. 

PMID- 23870108
TI  - Systematic review of the clinical effectiveness and cost-effectiveness, and
      economic evaluation, of denosumab for the treatment of bone metastases from solid
      tumours.
AB  - BACKGROUND: Denosumab offers an alternative, or additional, treatment for the
      prevention of skeletal-related events (SREs) in patients with bone metastases
      from solid tumours. OBJECTIVES: The aim of this review was to assess the clinical
      effectiveness and cost-effectiveness of denosumab, within its licensed
      indication, for the prevention of SREs in patients with bone metastases from
      solid tumours. DATA SOURCES: Databases searched were MEDLINE (1948 to April
      2011), EMBASE (1980 to March 2011), The Cochrane Library (all sections; Issue 1,
      2011) and Web of Science with Conference Proceedings (1970 to May 2011). REVIEW
      METHODS: Only randomised controlled trials (RCTs) assessing denosumab,
      bisphosphonates (BPs) or best supportive care (BSC) in patients with bone
      metastases were included. Systematic reviews and observational studies were used
      for safety and quality-of-life assessments. Study quality was assessed using the
      Cochrane risk of bias tool. Studies suitable for meta-analysis were synthesised
      using network meta-analysis (NMA). A systematic review was conducted for cost,
      quality-of-life and cost-effectiveness studies. The results of this informed the
      cost-utility modelling. This principally estimated the cost-effectiveness of
      denosumab relative to zoledronic acid for when BPs are currently recommended and
      relative to BSC when BPs are not recommended or are contraindicated. RESULTS: A
      literature search identified 39 studies (eight suitable for NMA). Denosumab was
      effective in delaying time to first SRE and reducing the risk of multiple SREs
      compared with zoledronic acid. Generally speaking, denosumab was similar to
      zoledronic acid for quality of life, pain, overall survival and safety. The NMA
      demonstrated that denosumab was more effective in delaying SREs than placebo, but
      was limited by numerous uncertainties. Cost-utility modelling results for
      denosumab relative to zoledronic acid were driven by the availability of the
      patient access scheme (PAS) for denosumab. Without this, denosumab was not
      estimated to be cost-effective compared with zoledronic acid. With it, the cost
      effectiveness ranged between dominance for breast and prostate cancer, to between
      L5400 and L15,300 per quality-adjusted life-year (QALY) for other solid tumours
      (OSTs) including non-small cell lung cancer (NSCLC) and L12,700 per QALY for
      NSCLC. Owing to small patient gains estimated, the cost-effectiveness of
      denosumab was very sensitive to the zoledronic acid price. Denosumab was not
      estimated to be cost-effective compared with BSC. LIMITATIONS: Only subgroup data
      were available for denosumab for NSCLC, and OSTs excluding NSCLC. The NMA was
      subject to numerous uncertainties. Owing to small patient gains estimated, the
      cost-effectiveness of denosumab was very sensitive to the zoledronic acid price.
      CONCLUSION: Denosumab, compared with zoledronic acid and placebo, is effective in
      delaying SREs, but is similar with regard to quality of life and pain. Cost
      effectiveness showed that without the PAS denosumab was not estimated to be cost
      effective relative to either zoledronic acid or BSC. With the PAS, denosumab was
      estimated to be cost-effective relative to zoledronic acid but not BSC. STUDY
      REGISTRATION: PROSPERO number CRD42011001418. FUNDING: The National Institute for
      Health Research Health Technology Assessment programme.

PMID- 23870109
TI  - Differences in PAR-2 activating potential by king crab (Paralithodes
      camtschaticus), salmon (Salmo salar), and bovine (Bos taurus) trypsin.
AB  - BACKGROUND: Salmon trypsin is shown to increase secretion of the pro-inflammatory
      cytokine interleukin (IL)-8 from human airway epithelial cells through activation
      of PAR-2. Secretion of IL-8 induced by king crab trypsin is observed in a
      different concentration range compared to salmon trypsin, and seems to be only
      partially related to PAR-2 activation. This report aim to identify differences in
      the molecular structure of king crab trypsin (Paralithodes camtschaticus)
      compared to salmon (Salmo salar) and bovine trypsin (Bos taurus) that might
      influence the ability to activate protease-activated receptor-2 (PAR-2). RESULTS:
      During purification king crab trypsin displayed stronger binding capacity to the
      anionic column used in fast protein liquid chromatography compared to fish
      trypsins, and was identified as a slightly bigger molecule. Measurements of
      enzymatic activity yielded no obvious differences between the trypsins tested.
      Molecular modelling showed that king crab trypsin has a large area with strong
      negative electrostatic potential compared to the smaller negative areas in bovine
      and salmon trypsins. Bovine and salmon trypsins also displayed areas with strong
      positive electrostatic potential, a feature lacking in the king crab trypsin.
      Furthermore we have identified 3 divergent positions (Asp196, Arg244, and Tyr247)
      located near the substrate binding pocket of king crab trypsin that might affect
      the binding and cleavage of PAR-2. CONCLUSION: These preliminary results indicate
      that electrostatic interactions could be of importance in binding, cleavage and
      subsequent activation of PAR-2.

PMID- 23870110
TI  - Mining differential top-k co-expression patterns from time course comparative
      gene expression datasets.
AB  - BACKGROUND: Frequent pattern mining analysis applied on microarray dataset
      appears to be a promising strategy for identifying relationships between gene
      expression levels. Unfortunately, too many itemsets (co-expressed genes) are
      identified by this analysis method since it does not consider the importance of
      each gene within biological processes to a cellular response and does not take
      into account temporal properties under biological treatment-control matched
      conditions in a microarray dataset. RESULTS: We propose a method termed TIIM (Top
      k Impactful Itemsets Miner), which only requires specifying a user-defined number
      k to explore the top k itemsets with the most significantly differentially co
      expressed genes between 2 conditions in a time course. To give genes different
      weights, a table with impact degrees for each gene was constructed based on the
      number of neighboring genes that are differently expressed in the dataset within
      gene regulatory networks. Finally, the resulting top-k impactful itemsets were
      manually evaluated using previous literature and analyzed by a Gene Ontology
      enrichment method. CONCLUSIONS: In this study, the proposed method was evaluated
      in 2 publicly available time course microarray datasets with 2 different
      experimental conditions. Both datasets identified potential itemsets with co
      expressed genes evaluated from the literature and showed higher accuracies
      compared to the 2 corresponding control methods: i) performing TIIM without
      considering the gene expression differentiation between 2 different experimental
      conditions and impact degrees, and ii) performing TIIM with a constant impact
      degree for each gene. Our proposed method found that several new gene regulations
      involved in these itemsets were useful for biologists and provided further
      insights into the mechanisms underpinning biological processes. The Java source
      code and other related materials used in this study are available at
      "http://websystem.csie.ncku.edu.tw/TIIM_Program.rar".

PMID- 23870111
TI  - Treatment of aortic root aneurysm and mitral valve pathology through a single
      aortotomy.
AB  - BACKGROUND: Aortic root aneurysms combined with lesions of the mitral valve
      requires synchronous operations. The conventional approach is to treat the two
      lesions through separate aortic and atrial incisions. METHODS: From May 2009 to
      August 2012, 28 transaortic mitral valve operations were performed. There were 23
      males and five females, the age ranged from 18 to 75 years, mean 41 +/- 16 years.
      The operative procedures included Bentall+MVR in 20 patients, Bentall+MVP in
      three patients, Bentall+total arch replacement+stent elephant trunk+MVP in one
      patient, Bentall+total arch replacement+stent elephant trunk+MVR in two patients,
      Bentall+MVP+CABG in two patients. Follow-up was completed for all patients, with
      a mean follow-up period of 22 +/- 10 months and a maximum of 42 months. RESULTS:
      Transaortic mitral valve surgery was successful for all patients. There was a
      reoperation in two patients for bleeding. In the MVP group, there was mild
      regurgitation in two cases before discharge, without further development during
      the follow-up. In the MVR group, there was paravalvular leakage in one patient
      three months later, which required repair. There were no deaths in the hospital
      and the follow-up period, and no valve-associated complication during the follow
      up period. The heart function of all patients during the follow-up period was
      Level I-II (NYHA). CONCLUSION: Transaortic mitral valve operation is a feasible
      surgical approach to treat patients with aortic root aneurysms combined with
      mitral valve lesions.

PMID- 23870112
TI  - Altered social and non-social decision-making in recreational and dependent
      cocaine users.
AB  - BACKGROUND: Maladaptive decision-making is assumed to be a core feature of
      cocaine addiction. Indeed, numerous studies have reported deficits in non-social
      decision-making tasks and reward-related impulsivity in dependent cocaine users.
      However, social decision-making has not been examined in cocaine users yet.
      Moreover, it is unknown if even recreational and non-dependent cocaine use is
      linked to decision-making deficits. Therefore, we investigated whether
      recreational and dependent cocaine users exhibit alterations in social and non
      social decision-making. METHOD: The performance of healthy controls (n = 68),
      recreational cocaine users (n = 68) and dependent cocaine users (n = 30) in
      classical decision-making paradigms (Iowa Gambling Task, Delay Discounting) and
      in social interaction paradigms (Distribution Game, Dictator Game) was assessed.
      RESULTS: Decisions in the social interaction tasks of both cocaine user groups
      were more self-serving compared with controls as cocaine users preferred higher
      monetary payoffs for themselves. In the Iowa Gambling Task, only dependent
      cocaine users were more likely to choose disadvantageous card decks, reflecting
      worse decision-making. They were also more likely to choose immediate smaller
      rewards over larger delayed rewards in the Delay Discounting task. CONCLUSIONS:
      Our results imply that both recreational and dependent cocaine users are more
      concerned with their own monetary gain when interacting with another person.
      Furthermore, primarily dependent cocaine users are less foresighted and more
      impulsive regarding immediate reward. Overall, social interaction deficits are
      already present in recreational users, while non-social decision-making deficits
      occur predominantly in dependent cocaine users. Thus, social interaction training
      and cognitive remediation strategies may improve treatment success and quality of
      life in cocaine dependence.

PMID- 23870113
TI  - Spiritual needs among patients with chronic pain diseases and cancer living in a
      secular society.
AB  - OBJECTIVE: Research has shown that several patients report unmet psychosocial and
      spiritual needs. While most studies focus on patients with advanced stages of
      disease, we intended to identify unmet spiritual needs in patients with chronic
      pain diseases and cancer living in a secular society. METHODS: In an anonymous
      cross-sectional study, standardized questionnaires were provided to German
      patients with chronic pain diseases (and cancer), i.e., Spiritual Needs
      Questionnaire (SpNQ), Spirituality/Religiosity and Coping (SpREUK-15), Spiritual
      Well-being (FACIT-Sp), Brief Multidimensional Life Satisfaction Scale,
      Interpretation of Illness Questionnaire, and Escape from Illness (Escape).
      RESULTS: We enrolled 392 patients (67% women, mean age 56.3 +/- 13.6 years; 61%
      Christian denomination) with chronic pain diseases (86%) and cancer (14%).
      Religious Needs (mean score 0.5 +/- 0.8 on the scale) and Existential Needs (0.8
      +/- 0.8 on the scale) were low, while needs for Inner Peace (1.5 +/- 0.9 on the
      scale) and Giving/Generativity were scored high (1.3 +/- 1.0 on the scale).
      Regression analyses indicated that Religious Needs can be predicted best by
      (religious) "Trust," the illness interpretation "call for help," and living with
      a partner; Existential Needs can be predicted by "call for help" and to a weaker
      extent by (religious) "Trust." Existential Needs are influenced negatively by the
      illness interpretation "challenge." Needs for Inner Peace were predicted only in
      trend by the illness interpretation "threat," and there were no significant
      predictors for the Giving/Generativity needs in the respective regression model.
      CONCLUSIONS: Patients with chronic pain diseases predominantly report needs
      related to inner peace and generative relatedness on a personal level, whereas
      needs related to transcendent relatedness were of minor relevance. Nevertheless,
      even religious "skeptics" can express specific religious needs, and these should
      be recognized. Addressing patients' specific needs and also supporting them in
      their struggle with chronic illness remain a challenging task for the modern
      health care system.

PMID- 23870114
TI  - Recognition for an innate explorer.
AB  - On June 5, 2013, Ruslan Medzhitov received the Else Kroner-Fresenius Immunology
      Award. This recognition goes to an individual who has had such an influence on
      basic and medical immunology that it is almost difficult to recall a time before
      his discoveries were made. But in reality, that time was not long ago. To mark
      this celebratory event, I highlight the conceptual revolution spurred by his
      work, which continues to inspire excitement today. 

PMID- 23870115
TI  - Differential geometry meets the cell.
AB  - A new study by Terasaki et al. highlights the role of physical forces in
      biological form by showing that connections between stacked endoplasmic reticulum
      cisternae have a shape well known in classical differential geometry, the
      helicoid, and that this shape is a predictable consequence of membrane physics. 

PMID- 23870116
TI  - Glia keep synapse distribution under wraps.
AB  - The wiring of the nervous system requires that axons navigate to the correct
      targets and maintain their correct positions during developmental growth. In this
      issue, Shao et al. (2013) now reveal a crucial new role for glia in preserving
      correct synaptic connectivity during developmental growth. 

PMID- 23870117
TI  - Born equal: dual safeguards for daughter cell size symmetry.
AB  - Development and homeostasis require repeated symmetric cell divisions, which in
      turn depend on a centered mitotic spindle. In this issue, Kiyomitsu and Cheeseman
      uncover two mechanisms that ensure correct spindle positioning in anaphase:
      cortical dynein for pulling the spindle to the cell center and asymmetric
      membrane elongation that adjusts the position of the cell center to the cleavage
      plane. 

PMID- 23870118
TI  - Aging: seeking mitonuclear balance.
AB  - Metabolic imbalances accompany the aging process in many organisms, and signaling
      mechanisms that allay or prevent these imbalances can extend lifespan. Two recent
      studies by Auwerx and colleagues, including one in this issue, identify a
      conserved signaling network centered on mitochondrial stress responses that
      promotes longevity in response to changes in mitochondrial translation and NAD(+)
      metabolism. 

PMID- 23870119
TI  - The intestinal crypt, a prototype stem cell compartment.
AB  - Due to its intense self-renewal kinetics and its simple repetitive architecture,
      the intestinal epithelium has become a prime model for studying adult stem cells
      in health and disease. Transgenic mouse models allow in vivo visualization and
      genetic lineage tracing of individual intestinal stem cells and their offspring.
      Fluorescently marked stem cells can be isolated for molecular analyses or can be
      cultured to build ever-expanding "mini-guts" in vitro. These studies are filling
      in the outlines of a robust homeostatic self-renewal process that defies some of
      the classical definitions of stem cell behavior, such as asymmetric division,
      quiescence, and exhaustion. 

PMID- 23870120
TI  - Stacked endoplasmic reticulum sheets are connected by helicoidal membrane motifs.
AB  - The endoplasmic reticulum (ER) often forms stacked membrane sheets, an
      arrangement that is likely required to accommodate a maximum of membrane-bound
      polysomes for secretory protein synthesis. How sheets are stacked is unknown.
      Here, we used improved staining and automated ultrathin sectioning electron
      microscopy methods to analyze stacked ER sheets in neuronal cells and secretory
      salivary gland cells of mice. Our results show that stacked ER sheets form a
      continuous membrane system in which the sheets are connected by twisted membrane
      surfaces with helical edges of left- or right-handedness. The three-dimensional
      structure of tightly stacked ER sheets resembles a parking garage, in which the
      different levels are connected by helicoidal ramps. A theoretical model explains
      the experimental observations and indicates that the structure corresponds to a
      minimum of elastic energy of sheet edges and surfaces. The structure allows the
      dense packing of ER sheets in the restricted space of a cell. 

PMID- 23870121
TI  - SET1 and p300 act synergistically, through coupled histone modifications, in
      transcriptional activation by p53.
AB  - The H3K4me3 mark in chromatin is closely correlated with actively transcribed
      genes, although the mechanisms involved in its generation and function are not
      fully understood. In vitro studies with recombinant chromatin and purified human
      factors demonstrate a robust SET1 complex (SET1C)-mediated H3K4 trimethylation
      that is dependent upon p53- and p300-mediated H3 acetylation, a corresponding
      SET1C-mediated enhancement of p53- and p300-dependent transcription that reflects
      a primary effect of SET1C through H3K4 trimethylation, and direct SET1C-p53 and
      SET1C-p300 interactions indicative of a targeted recruitment mechanism.
      Complementary cell-based assays demonstrate a DNA-damage-induced p53-SET1C
      interaction, a corresponding enrichment of SET1C and H3K4me3 on a p53 target gene
      (p21/WAF1), and a corresponding codependency of H3K4 trimethylation and
      transcription upon p300 and SET1C. These results establish a mechanism in which
      SET1C and p300 act cooperatively, through direct interactions and coupled histone
      modifications, to facilitate the function of p53. 

PMID- 23870122
TI  - An epigenetic trap stabilizes singular olfactory receptor expression.
AB  - The molecular mechanisms regulating olfactory receptor (OR) expression in the
      mammalian nose are not yet understood. Here, we identify the transient expression
      of histone demethylase LSD1 and the OR-dependent expression of adenylyl cyclase 3
      (Adcy3) as requirements for initiation and stabilization of OR expression. As a
      transcriptional coactivator, LSD1 is necessary for desilencing and initiating OR
      transcription, but as a transcriptional corepressor, it is incompatible with
      maintenance of OR expression, and its downregulation is imperative for stable OR
      choice. Adcy3, a sensor of OR expression and a transmitter of an OR-elicited
      feedback, mediates the downregulation of LSD1 and promotes the differentiation of
      olfactory sensory neurons (OSNs). This novel, three-node signaling cascade locks
      the epigenetic state of the chosen OR, stabilizes its singular expression, and
      prevents the transcriptional activation of additional OR alleles for the life of
      the neuron. 

PMID- 23870123
TI  - Synapse location during growth depends on glia location.
AB  - Synaptic contacts are largely established during embryogenesis and are then
      maintained during growth. To identify molecules involved in this process, we
      conducted a forward genetic screen in C. elegans and identified cima-1. In cima-1
      mutants, synaptic contacts are correctly established during embryogenesis, but
      ectopic synapses emerge during postdevelopmental growth. cima-1 encodes a solute
      carrier in the SLC17 family of transporters that includes sialin, a protein that
      when mutated in humans results in neurological disorders. cima-1 does not
      function in neurons but rather functions in the nearby epidermal cells to
      correctly position glia during postlarval growth. Our findings indicate that CIMA
      1 antagonizes the FGF receptor (FGFR), and does so most likely by inhibiting
      FGFR's role in epidermal-glia adhesion rather than signaling. Our data suggest
      that epidermal-glia crosstalk, in this case mediated by a transporter and the FGF
      receptor, is vital to preserve embryonically derived circuit architecture during
      postdevelopmental growth.

PMID- 23870124
TI  - A network of cadherin-mediated interactions polarizes growth cones to determine
      targeting specificity.
AB  - Neuronal growth cones select synaptic partners through interactions with multiple
      cell surfaces in their environment. Many of these interactions are adhesive, yet
      it is unclear how growth cones integrate adhesive cues to direct their movements.
      Here, we examine the mechanisms that enable photoreceptors in the Drosophila
      visual system to choose synaptic partners. We demonstrate that the classical
      cadherin, N-cadherin, and an atypical cadherin, Flamingo, act redundantly to
      instruct the targeting choices made by every photoreceptor axon. These molecules
      gradually bias the spatial distribution of growth cone filopodia, polarizing each
      growth cone toward its future synaptic target before direct contact with the
      target occurs. We demonstrate that these molecules are localized to distinct
      subcellular domains and create a network of adhesive interactions distributed
      across many growth cones. Because this network comprises multiple redundant
      interactions, a complex wiring diagram can be constructed with extraordinary
      fidelity, suggesting a general principle. 

PMID- 23870125
TI  - Noncanonical autophagy promotes the visual cycle.
AB  - Phagocytosis and degradation of photoreceptor outer segments (POS) by retinal
      pigment epithelium (RPE) is fundamental to vision. Autophagy is also responsible
      for bulk degradation of cellular components, but its role in POS degradation is
      not well understood. We report that the morning burst of RPE phagocytosis
      coincided with the enzymatic conversion of autophagy protein LC3 to its lipidated
      form. LC3 associated with single-membrane phagosomes containing engulfed POS in
      an Atg5-dependent manner that required Beclin1, but not the autophagy
      preinitiation complex. The importance of this process was verified in mice with
      Atg5-deficient RPE cells that showed evidence of disrupted lysosomal processing.
      These mice also exhibited decreased photoreceptor responses to light stimuli and
      decreased chromophore levels that were restored with exogenous retinoid
      supplementation. These results establish that the interplay of phagocytosis and
      autophagy within the RPE is required for both POS degradation and the maintenance
      of retinoid levels to support vision.

PMID- 23870126
TI  - Marking and measuring single microtubules by PRC1 and kinesin-4.
AB  - Error-free cell division depends on the assembly of the spindle midzone, a
      specialized array of overlapping microtubules that emerges between segregating
      chromosomes during anaphase. The molecular mechanisms by which a subset of
      dynamic microtubules from the metaphase spindle are selected and organized into a
      stable midzone array are poorly understood. Here, we show using in vitro
      reconstitution assays that PRC1 and kinesin-4, two microtubule-associated
      proteins required for midzone assembly, can tag microtubule plus ends.
      Remarkably, the size of these tags is proportional to filament length. We
      determine the crystal structure of the PRC1 homodimer and map the protein-protein
      interactions needed for tagging microtubule ends. Importantly, length-dependent
      microtubule plus-end-tagging by PRC1 is also observed in dividing cells. Our
      findings suggest how biochemically similar microtubules can be differentially
      marked, based on length, for selective regulation during the formation of
      specialized arrays, such as those required for cytokinesis.

PMID- 23870127
TI  - Cortical dynein and asymmetric membrane elongation coordinately position the
      spindle in anaphase.
AB  - Mitotic spindle position defines the cell-cleavage site during cytokinesis.
      However, the mechanisms that control spindle positioning to generate equal-sized
      daughter cells remain poorly understood. Here, we demonstrate that two mechanisms
      act coordinately to center the spindle during anaphase in symmetrically dividing
      human cells. First, the spindle is positioned directly by the microtubule-based
      motor dynein, which we demonstrate is targeted to the cell cortex by two distinct
      pathways: a Galphai/LGN/NuMA-dependent pathway and a 4.1G/R and NuMA-dependent,
      anaphase-specific pathway. Second, we find that asymmetric plasma membrane
      elongation occurs in response to spindle mispositioning to alter the cellular
      boundaries relative to the spindle. Asymmetric membrane elongation is promoted by
      chromosome-derived Ran-GTP signals that locally reduce Anillin at the growing
      cell cortex. In asymmetrically elongating cells, dynein-dependent spindle
      anchoring at the stationary cell cortex ensures proper spindle positioning. Our
      results reveal the anaphase-specific spindle centering systems that achieve equal
      sized cell division. 

PMID- 23870128
TI  - Methionine inhibits autophagy and promotes growth by inducing the SAM-responsive
      methylation of PP2A.
AB  - Autophagy is a process of cellular self-digestion induced by various forms of
      starvation. Although nitrogen deficit is a common trigger, some yeast cells
      induce autophagy upon switch from a rich to minimal media without nitrogen
      starvation. We show that the amino acid methionine is sufficient to inhibit such
      non-nitrogen-starvation (NNS)-induced autophagy. Methionine boosts synthesis of
      the methyl donor, S-adenosylmethionine (SAM). SAM inhibits autophagy and promotes
      growth through the action of the methyltransferase Ppm1p, which modifies the
      catalytic subunit of PP2A in tune with SAM levels. Methylated PP2A promotes
      dephosphorylation of Npr2p, a component of a conserved complex that regulates NNS
      autophagy and other growth-related processes. Thus, methionine and SAM levels
      represent a critical gauge of amino acid availability that is sensed via the
      methylation of PP2A to reciprocally regulate cell growth and autophagy. 

PMID- 23870129
TI  - Sulfur amino acids regulate translational capacity and metabolic homeostasis
      through modulation of tRNA thiolation.
AB  - Protein translation is an energetically demanding process that must be regulated
      in response to changes in nutrient availability. Herein, we report that
      intracellular methionine and cysteine availability directly controls the
      thiolation status of wobble-uridine (U34) nucleotides present on lysine,
      glutamine, or glutamate tRNAs to regulate cellular translational capacity and
      metabolic homeostasis. tRNA thiolation is important for growth under
      nutritionally challenging environments and required for efficient translation of
      genes enriched in lysine, glutamine, and glutamate codons, which are enriched in
      proteins important for translation and growth-specific processes. tRNA thiolation
      is downregulated during sulfur starvation in order to decrease sulfur consumption
      and growth, and its absence leads to a compensatory increase in enzymes involved
      in methionine, cysteine, and lysine biosynthesis. Thus, tRNA thiolation enables
      cells to modulate translational capacity according to the availability of sulfur
      amino acids, establishing a functional significance for this conserved tRNA
      nucleotide modification in cell growth control.

PMID- 23870132
TI  - SnapShot: pathobiology of Alzheimer's disease.

PMID- 23870130
TI  - The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of
      Mitochondrial UPR and FOXO Signaling.
AB  - NAD(+) is an important cofactor regulating metabolic homeostasis and a rate
      limiting substrate for sirtuin deacylases. We show that NAD(+) levels are reduced
      in aged mice and Caenorhabditis elegans and that decreasing NAD(+) levels results
      in a further reduction in worm lifespan. Conversely, genetic or pharmacological
      restoration of NAD(+) prevents age-associated metabolic decline and promotes
      longevity in worms. These effects are dependent upon the protein deacetylase sir
      2.1 and involve the induction of mitonuclear protein imbalance as well as
      activation of stress signaling via the mitochondrial unfolded protein response
      (UPR(mt)) and the nuclear translocation and activation of FOXO transcription
      factor DAF-16. Our data suggest that augmenting mitochondrial stress signaling
      through the modulation of NAD(+) levels may be a target to improve mitochondrial
      function and prevent or treat age-associated decline. 

PMID- 23870133
TI  - Mitochondrial DNA variant m.15218A > G in Finnish epilepsy patients who have
      maternal relatives with epilepsy, sensorineural hearing impairment or diabetes
      mellitus.
AB  - BACKGROUND: Mitochondrial diseases caused by mutations in mitochondrial DNA
      (mtDNA) affect tissues with high energy demand. Epilepsy is one of the
      manifestations of mitochondrial dysfunction when the brain is affected. We have
      studied here 79 Finnish patients with epilepsy and who have maternal first- or
      second-degree relatives with epilepsy, sensorineural hearing impairment or
      diabetes mellitus. METHODS: The entire mtDNA was studied by using conformation
      sensitive gel electrophoresis and PCR fragments that differed in mobility were
      directly sequenced. RESULTS: We found a common nonsynonymous variant m.15218A > G
      (p.T158A, MTCYB) that occurs in haplogroup U5a1 to be more frequent in patients
      with epilepsy. The m.15218A > G variant was present in five patients with
      epilepsy and in four out of 403 population controls (p = 0.0077). This variant
      was present in two branches in the phylogenetic network constructed on the basis
      of mtDNA variation among the patients. Three algorithms predicted that m.15218A >
      G is damaging in effect. CONCLUSIONS: We suggest that the m.15218A > G variant is
      mildly deleterious and that mtDNA involvement should be considered in patients
      with epilepsy and who have a maternal history of epilepsy, sensorineural hearing
      impairment or diabetes mellitus.

PMID- 23870134
TI  - Association of tumor necrosis factor-alpha promoter variants with risk of HPV
      associated oral squamous cell carcinoma.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) plays an important role in
      inflammation, immunity, and defense against infection and clearance of human
      papillomavirus (HPV). Thus, genetic variants may modulate individual
      susceptibility to HPV-associated oral squamous cell carcinoma (OSCC). METHODS: In
      this study we genotyped four common single nucleotide polymorphisms (SNPs) in the
      TNF-alpha promoter [ -308G > A(rs1800629), -857C > T (rs1799724), -863C > A
      (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325
      OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell
      carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable
      logistic regression models were used to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: We found that HPV16 seropositivity alone was
      associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1-4.6), and such
      risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16
      seropositivity and variant genotypes for each SNP had the highest risk when using
      patients with HPV16 seronegativity and a wild-type genotype as a comparison
      group. Moreover, similar results were observed for the combined risk genotypes of
      four variants and all such significant associations were more pronounced in
      several subgroups, particularly in SCCOP patients and never smokers. Notably, the
      combined risk genotypes of four variants were also significantly associated with
      tumor HPV-positive SCCOP. CONCLUSION: Taken together, these results suggest that
      TNF-alpha SNPs may individually or, more likely, jointly affect individual
      susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers.
      Validation of our findings is warranted.

PMID- 23870135
TI  - Use of emergency department services by women victims of violence in Lazio
      region, Italy.
AB  - BACKGROUND: Violence against women is a significant health problem and a hidden
      phenomenon, in Italy that about 31% of the women have been victims of violence
      once in life. Aims of this study are to describe characteristics of women victims
      of violence (VV) attending the EDs in the Lazio region in 2008 and to illustrate
      the frequency and characteristics of previous ED visits. METHODS: Using the
      Emergency Information System, visits of women, (15-49 years), in the 60 EDs, for
      a violent trauma have been analysed. For each VV identified, we considered the
      last episode and searched for ED attendances in a six year period (2003-08) in
      order to identify other visits. We performed descriptive analyses of socio
      demographic and clinical factors of VV and we analyzed the impact previous ED
      visits. We compared ED utilization of women VV with a random sample of women with
      the same age distribution who gave birth in 2008. RESULTS: In 2008, 7,725 ED
      attendances of women VV were found (1.1% of the ED visits) corresponding to 6,936
      women (prevalence = 52.0x10,000). The mean number of ED visits for each woman in
      five years was 5.0 (1-190). Prevalent diagnoses were contusions (45.8%), neurotic
      disorders (5.4%) complications of medical care (6.3%). The women were young,
      approximately 70% were residents in Rome or the surrounding areas. Foreign women
      were three times more likely to visit the ED for intentional injuries than were
      Italian women (114.1 vs 44.4 per 10.000). CONCLUSIONS: This study shows high
      prevalence of violence against women in Lazio region, Italy. Most of the women
      have been visited by the ED several times before the violent episode, often with
      traumas. ED medical and nursing staff should be prepared and trained to
      successfully manage victims of violence.

PMID- 23870131
TI  - Genome-wide generation and systematic phenotyping of knockout mice reveals new
      roles for many genes.
AB  - Mutations in whole organisms are powerful ways of interrogating gene function in
      a realistic context. We describe a program, the Sanger Institute Mouse Genetics
      Project, that provides a step toward the aim of knocking out all genes and
      screening each line for a broad range of traits. We found that hitherto
      unpublished genes were as likely to reveal phenotypes as known genes, suggesting
      that novel genes represent a rich resource for investigating the molecular basis
      of disease. We found many unexpected phenotypes detected only because we screened
      for them, emphasizing the value of screening all mutants for a wide range of
      traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty
      two percent of genes were essential for viability, and these were less likely to
      have a paralog and more likely to contribute to a protein complex than other
      genes. Phenotypic data and more than 900 mutants are openly available for further
      analysis. PAPERCLIP: 

PMID- 23870136
TI  - The impact of an infant's severe congenital heart disease on the family: a
      prospective cohort study.
AB  - OBJECTIVE: The aim of this article is to investigate the impact of a child's
      severe congenital heart disease on the family and to prospectively examine the
      influence of disease specific and psychosocial factors on the family. DESIGN: A
      prospective cohort study. PATIENTS: Parents of 104 infants who had undergone
      cardiopulmonary bypass surgery before the age of 12 months for congenital heart
      disease were included. INTERVENTIONS: None. OUTCOME MEASURES: Parents completed
      the generic Impact on Family scale and a social support questionnaire; a large
      number of medical data were extracted from the patients' hospital records.
      RESULTS: Parents most frequently reported that they were thinking about not
      having more children and living on a "roller coaster." No difference was found in
      the total Impact on Family scale score between fathers and mothers. The presence
      of a genetic disorder in the child and lower levels of perceived social support
      was significantly associated with a greater impact on the family. CONCLUSIONS:
      The impact of an infant's congenital heart disease on the family is determined
      both by child's medical condition and family's psychosocial factors. Families
      with poorer social support network may have the greatest need for professional
      interventions, especially if their child has an underlying genetic disorder.

PMID- 23870138
TI  - Percentages of oleic acid and arachidonic acid are inversely related in
      phospholipids of human sera.
AB  - BACKGROUND: Many health effects of oils rich in oleic acid (18:1 n9) seem to be
      opposite those of arachidonic acid (20:4 n6), i.e. concerning cardiovascular
      risk. In recent study in rats we observed that percentages of oleic acid and
      arachidonic acid were inversely related in total serum lipids. In the present
      work we investigate whether an inverse relationship between this couple of fatty
      acids also exists in the phospholipid fraction of human sera. METHODS: The study
      group consisted of 11 men and 35 women. Mean age was 23.8 +/- 2.5 years (mean +/-
      SD), and the body mass index was 23.5 +/- 3.2 kg/m2. After fasting overnight,
      blood was drawn and the concentration of fatty acids in serum phospholipids was
      determined, using gas chromatography. We studied the association between
      percentages of oleic acid and arachidonic acid using bivariate correlations
      (Pearson), and multiple linear regressions. RESULTS: We found an inverse
      relationship (r = -0.563, p < 0.001; n = 46) between % oleic acid and %
      arachidonic acid in the serum phosholipid fraction of the 46 fasting subjects. By
      multiple linear regression, and % 20:4 n6 as the dependent variable, the inverse
      association with % 18:1 n9 persisted when controlling for sex, age, body mass
      index, and percentages of the other fatty acids measured (t = -17.6, p < 0.001).
      Per cent 20:4 n6 seemed to correlate negatively (r = -0.289, p = 0.05) with the
      (18:1 n9)/(18:0) ratio, estimating Delta9 desaturase activity, and % oleic acid
      correlated negatively (r = -0.321, p = 0.029) with the (20:4)/(18:2) ratio,
      estimating desaturases/elongase activities. CONCLUSIONS: In a group of healthy
      human subjects, percentages of oleic acid and arachidonic acid were inversely
      related, and the inverse association persisted when controlling for possible
      confounding variables. The findings might contribute to explain positive health
      effects of foods rich in oleic acid.

PMID- 23870137
TI  - Balancing chromatin remodeling and histone modifications in transcription.
AB  - Chromatin remodelers use the energy of ATP hydrolysis to reposition or evict
      nucleosomes or to replace canonical histones with histone variants. By regulating
      nucleosome dynamics, remodelers gate access to the underlying DNA for
      replication, repair, and transcription. Nucleosomes are subject to extensive post
      translational modifications that can recruit regulatory proteins or alter the
      local chromatin structure. Just as extensive crosstalk has been observed between
      different histone post-translational modifications, there is growing evidence for
      both coordinated and antagonistic functional relations between nucleosome
      remodeling and modifying machineries. Defining the combined functions of the
      complexes that alter nucleosome interactions, position, and stability is key to
      understanding processes that require access to DNA, particularly with growing
      appreciation of their contributions to human health and disease. Here, we
      highlight recent advances in the interactions between histone modifications and
      the imitation-switch (ISWI) and chromodomain helicase DNA-binding protein 1
      (CHD1) chromatin remodelers from studies in budding yeast, fission yeast, flies,
      and mammalian cells, with a focus on yeast. 

PMID- 23870139
TI  - Noncoding roX RNA remodeling triggers fly dosage compensation complex assembly.
AB  - Spreading of dosage compensation over the X chromosome in Drosophila males
      requires the noncoding roX1 and roX2 RNAs. In this issue, Ilik et al. (2013) and
      Maenner et al. (2013) show that these RNAs contain discrete binding sites that
      are remodeled during assembly of the dosage compensation complex.

PMID- 23870140
TI  - Acetylphosphate: a novel link between lysine acetylation and intermediary
      metabolism in bacteria.
AB  - In this issue of Molecular Cell, Weinert et al. (2013) demonstrate that the
      intermediary metabolite acetyl-phosphate is an important acetyl donor that
      contributes to global protein acetylation in growth-arrested E. coli.

PMID- 23870141
TI  - The cGAS-STING pathway for DNA sensing.
AB  - The nucleotidyl transferase cGAS, its second-messenger product cGAMP, and the
      cGAMP sensor STING form the basic mechanism of DNA sensing in the cytoplasm of
      mammalian cells. Several new reports now uncover key structural features
      associated with DNA recognition by cGAS and the catalytic mechanisms of cGAMP
      generation. Concurrent studies also reveal unique phosphodiester linkages in
      endogenous cGAMP that distinguish it from microbial cGAMP and other cyclic
      dinucleotides. Together, these studies provide a new perspective on DNA
      recognition in the innate immune system. 

PMID- 23870143
TI  - ATP-dependent roX RNA remodeling by the helicase maleless enables specific
      association of MSL proteins.
AB  - Dosage compensation in Drosophila involves a global activation of genes on the
      male X chromosome. The activating complex (MSL-DCC) consists of male-specific
      lethal (MSL) proteins and two long, noncoding roX RNAs. The roX RNAs are
      essential for X-chromosomal targeting, but their contributions to MSL-DCC
      structure and function are enigmatic. Conceivably, the RNA helicase MLE, itself
      an MSL subunit, is actively involved in incorporating roX into functional DCC. We
      determined the secondary structure of roX2 and mapped specific interaction sites
      for MLE in vitro. Upon addition of ATP, MLE disrupted a functionally important
      stem loop in roX2. This RNA remodeling enhanced specific ATP-dependent
      association of MSL2, the core subunit of the MSL-DCC, providing a link between
      roX and MSL subunits. Probing the conformation of roX in vivo revealed a
      remodeled stem loop in chromatin-bound roX2. The active remodeling of a stable
      secondary structure by MLE may constitute a rate-limiting step for MSL-DCC
      assembly.

PMID- 23870144
TI  - The development of anesthesiology in oral and maxillofacial surgery.
AB  - No legitimate history of anesthesiology can exclude the contributions of American
      dentistry. Similarly, no history of anesthesiology in dentistry can exclude the
      contributions of oral and maxillofacial surgery (OMS). Many contributions of OMS
      to the art and science of anesthesiology have been singular, cutting edge when
      introduced, have stood the test of time, and have subsequently been universally
      incorporated into the general discipline. The process continues to this day with
      regard to the innovations and refinements OMS has proffered to the control of
      anxiety and pain. This article offers a brief review of some of these gifts. 

PMID- 23870142
TI  - Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage
      compensation in Drosophila.
AB  - Dosage compensation in Drosophila is an epigenetic phenomenon utilizing proteins
      and long noncoding RNAs (lncRNAs) for transcriptional upregulation of the male X
      chromosome. Here, by using UV crosslinking followed by deep sequencing, we show
      that two enzymes in the Male-Specific Lethal complex, MLE RNA helicase and MSL2
      ubiquitin ligase, bind evolutionarily conserved domains containing tandem stem
      loops in roX1 and roX2 RNAs in vivo. These domains constitute the minimal RNA
      unit present in multiple copies in diverse arrangements for nucleation of the MSL
      complex. MLE binds to these domains with distinct ATP-independent and ATP
      dependent behavior. Importantly, we show that different roX RNA domains have
      overlapping function, since only combinatorial mutations in the tandem stem-loops
      result in severe loss of dosage compensation and consequently male-specific
      lethality. We propose that repetitive structural motifs in lncRNAs could provide
      plasticity during multiprotein complex assemblies to ensure efficient targeting
      in cis or in trans along chromosomes.

PMID- 23870145
TI  - Determining the appropriate oral surgery anesthesia modality, setting, and team.
AB  - This article reviews the anesthesia modalities available to the practicing oral
      and maxillofacial surgeon, including the anesthesia TEAM makeup. If office-based
      anesthesia is not the best option for the patient, alternative locations are
      discussed including out-patient surgery centers and hospitals. The American
      Association of Oral and Maxillofacial Surgeons (AAOMS) has fought long and hard
      to establish and maintain our ability to provide office-based anesthesia. This is
      our Standard of Care! 

PMID- 23870146
TI  - Anesthesia equipment for the oral and maxillofacial surgery practice.
AB  - The physical design of an oral and maxillofacial surgeon's office is highly
      individualized and unique. Every office must incorporate certain essential
      equipment and features to safely deliver office anesthesia, regardless of the
      scope of anesthesia services provided. Furthermore, the office design and
      anesthesia armamentarium must take into account patient safety and comfort. This
      article discusess the necessary elements, ranging from preanesthesia assessment
      forms and intraoperative records to office design, anesthesia monitors, and
      equipment related to the safe and successful administration of office-based
      anesthesia by oral and maxillofacial surgeons and their staff. 

PMID- 23870147
TI  - Adult airway evaluation in oral surgery.
AB  - Patients with a history of difficult intubation or with conditions associated
      with difficult airway should be approached with organized primary and secondary
      plans for airway management. When these potential problems are detected, patient
      safety may be improved with use of advanced airway management techniques and
      equipment. Additionally, patient referral for consultation and/or management at
      facilities where advanced airway management practitioners and equipment are
      available may be beneficial in some cases. 

PMID- 23870148
TI  - Common medical illnesses that affect anesthesia and their anesthetic management.
AB  - Patients undergoing an office-based anesthetic require a thorough preoperative
      evaluation to identify medical illnesses and undertake appropriate investigations
      or studies. This article addresses common medical illnesses seen in oral surgery
      offices and provides insight into their anesthetic management, concentrating on
      open-airway office-based anesthesia. 

PMID- 23870149
TI  - Pediatric sedation and anesthesia for the oral surgeon.
AB  - Even simple oral and maxillofacial surgical procedures can become challenging
      when the child patient has a high degree of fear and anxiety. This article
      reviews differences in anatomy and physiology between the adult and pediatric
      patient, preanesthetic assessment, fasting guidelines, and choices of sedation
      routes, and discusses equipment options for the management of pediatric
      anesthesia. After reflection on these topics and based on training and
      experience, oral and maxillofacial surgeons can decide the ages of patients,
      medical comorbidities, and techniques with which they are comfortable in
      performing surgery in their offices in a safe and effective manner. 

PMID- 23870151
TI  - Anesthesia.

PMID- 23870150
TI  - Managing the untoward anesthetic event in an oral and maxillofacial surgery
      practice.
AB  - The safe and efficient use of outpatient surgical anesthesia modalities is a
      significant part of the training and expertise of the oral and maxillofacial
      surgeon. Although adverse outcomes are rare, they can have considerable traumatic
      psychological and professional consequences for the surgeon involved. The goal of
      this article is to develop guidelines to educate the doctor, the second victim,
      on how to manage a bad outcome and how to navigate through a difficult and
      arduous process. 

PMID- 23870152
TI  - Obesity paradox in coronary artery bypass grafting: myth or reality?
AB  - OBJECTIVE: A high body mass index has been suggested to be protective in patients
      with coronary artery disease and in those undergoing coronary artery bypass
      grafting (CABG). However, these conflicting results might be related to the
      different risk profiles among the various body mass index categories. We sought
      to clarify the effect of varying degrees of excessive body weight on hard
      clinical outcomes in patients undergoing CABG. METHODS: A retrospective analysis
      of prospectively collected data was conducted to investigate the effect of a high
      body mass index on early and late mortality after first-time isolated CABG.
      Propensity score matching was used to adjust for confounding factors. RESULTS:
      The study sample consisted of 3269 normal weight, 6662 overweight, 3821 obese,
      and 211 morbidly obese patients. After matching, early mortality was not affected
      by overweight (mean difference, 0.7%; 95% confidence interval [CI], -0.2% to
      1.5%), obesity (mean difference, 0.5%; 95% CI, -0.7% to 1.7%), and morbid obesity
      (mean difference, 1.6%; 95% CI, -1.0% to 1.0%), regardless of the patients' risk
      profile according to the European system for cardiac operative risk evaluation.
      Overweight status was not protective for late death (hazard ratio, 1.05; 95% CI,
      0.9-1.08; P = .4). Compared with normal weight patients, both obese and morbidly
      obese patients had a higher risk of late death (hazard ratio, 1.22; 95% CI, 1.07
      2.66; P = .006 for obese patients; hazard ratio, 1.36; 95% CI, 0.74-2.49; P = .3
      for morbidly obese patients). CONCLUSIONS: Obesity did not increase operative
      mortality, but it was associated with reduced late survival in patients
      undergoing primary isolated CABG. Our results raise concerns in supporting any
      protective effect of obesity in cardiovascular disease, specifically in patients
      undergoing surgical myocardial revascularization.

PMID- 23870153
TI  - Food and Drug Administration commentary on "a new paradigm for obtaining
      marketing approval for pediatric-sized prosthetic heart valves".

PMID- 23870154
TI  - Surgical correction of aortic valve insufficiency after left ventricular assist
      device implantation.
AB  - OBJECTIVES: New-onset aortic insufficiency (AI) can be encountered after
      instituting mechanical circulatory support and seems more common and severe with
      continuous flow (CF) left ventricular assist devices (LVADs) compared with
      pulsatile devices. Treatment algorithms for de novo, post-LVAD AI have not been
      well defined. In the present report, we have described 6 patients who underwent
      aortic valve surgery for new-onset post-LVAD AI. METHODS: From 2005 to 2011, 271
      patients underwent LVAD implantation. Of these LVADs, 225 were CF devices (203
      HeartMate II devices, Thoratec Corp, Pleasanton, Calif; and 22 HVAD devices,
      HeartWare Intl, Inc, Framingham, Mass). The patients were examined for new-onset
      severe AI requiring surgical intervention. RESULTS: During follow-up, 6 CF LVAD
      patients developed new, severe AI that was accompanied by heart failure. After
      medical therapy had failed, 4 patients underwent redo sternotomy for aortic valve
      procedures (1 bioprosthetic valve replacement, 1 Dacron patch closure, and 2
      aortic valve repairs), and 2 patients underwent transcatheter aortic valve
      procedure, with 1 requiring revision by open surgery for aortic valve
      replacement. Of the 6 patients, 5 experienced significant improvement in
      functional capacity and symptoms. One patient died postoperatively secondary to
      multiorgan failure and sepsis. CONCLUSIONS: Surgical treatment of post-LVAD AI
      with aortic valve oversewing or leaflet repair or by bioprosthetic aortic valve
      replacement is effective at restoring functional capacity for CF LVAD patients
      who develop symptomatic, severe AI and can be performed safely with good results.
      Various transcatheter approaches to these difficult problems are also available
      and offer less invasive alternatives to conventional surgery.

PMID- 23870155
TI  - Cardiothoracic surgery residency training: past, present, and future.
AB  - BACKGROUND: A dramatic transformation of cardiothoracic surgical education has
      evolved over the past few decades. METHODS: We begin by presenting recognized
      catalysts of this change, organized by whom they primarily affect: the trainees,
      the trainers, and the profession as a whole. Our trainees' prior training is
      different, and their current demographics and priorities have changed. There is
      less incentive to teach, with time-honored traditions of education inadequate to
      meet the needs of trainees. Concurrently, our profession has to adjust to new
      regulations, increasing financial constraints, and an expanding body of knowledge
      and technology. To address these issues requires developing new models of
      education and assessment that can thrive in today's environment. We discuss
      efforts in the United States and abroad, including new training paradigms ranging
      from restructuring existing models to novel approaches (eg, competency-based
      training). Training tools are being developed, such as online instruction,
      simulation-based learning, and regular student-centered assessments. Finally,
      models that recognize and reward teaching as a scholarly activity are being
      implemented. CONCLUSIONS: Like the radical advances we have witnessed in surgical
      therapy, surgical education requires creative and perhaps disruptive changes if
      we are to continue to produce well-trained additions to our professional ranks.

PMID- 23870156
TI  - Dynamic characterization of aortic annulus geometry and morphology with
      multimodality imaging: predictive value for aortic regurgitation after
      transcatheter aortic valve replacement.
AB  - BACKGROUND: Patients undergoing transcatheter aortic valve replacement (TAVR), as
      compared with those undergoing surgical aortic valve replacement (AVR), have
      higher postprocedural aortic regurgitation (AR), associated with higher
      mortality. We hypothesized that reduced annular deformation is associated with
      higher postprocedural AR and sought to assess incremental value of assessment of
      aortic annular deformation in prediction of post-TAVR AR. METHODS: We included 87
      patients with high-risk severe aortic stenosis (AS) (81 +/- 10 years, 54% men)
      who underwent preprocedural echocardiography and contrast-enhanced (4
      dimensional) multidetector computed tomography (MDCT) of the aortic root,
      followed by TAVR (n = 55) or surgical AVR (n = 32). On MDCT, minimal/maximal
      annular circumference, circumferential deformation (maximum-minimum over cardiac
      cycle), and eccentricity (largest/smallest diameter during systole) were
      calculated. Degree of commissural/annular calcification was graded
      semiquantitatively (scale 1-3). Oversizing/undersizing of the prosthesis during
      TAVR was assessed. RESULTS: Pre-AVR aortic valve area (0.6 +/- 0.1 vs 0.6 +/- 0.1
      cm(2)), mean aortic valve gradient (46 +/- 14 vs 45 +/- 11 mm Hg), AR (1 +/- 0.8
      vs 0.9 +/- 0.7), maximal annular circumference (8 +/- 1 vs 7.9 +/- 0.8 cm),
      annular deformation (0.3 +/- 0.1 vs 0.3 +/- 0.1 cm), eccentricity (1.2 +/- 0.1 vs
      1.2 +/- 0.1), commissural (2.1 +/- 0.6 vs 2 +/- 0.7), and annular calcification
      scores (1.7 +/- 0.8 vs 1.7 +/- 0.8) were similar in TAVR and surgical AVR groups
      (P = not significant). A higher proportion of patients had >= mild AR in the TAVR
      than in the surgical AVR group (58% vs 34%; P < .03). In TAVR patients, reduced
      annular deformation (P = .01) predicted postprocedural AR, in addition to
      prosthesis undersizing (P = .03) and higher annular calcification (P = .03).
      CONCLUSIONS: Residual post-TAVR AR is predicted by reduced aortic annular
      deformity, higher annular calcification, and prosthesis undersizing. Pre-TAVR 4
      dimensional annular assessment aids in prediction of post-TAVR AR.

PMID- 23870157
TI  - Are intraoperative precursor events associated with postoperative major adverse
      events?
AB  - OBJECTIVES: Precursor events are undesirable events that can lead to a subsequent
      adverse event and have been associated with postoperative mortality. The purpose
      of the present study was to determine whether precursor events are associated
      with a composite endpoint of major adverse cardiac events (MACE) (death, acute
      renal failure, stroke, infection) in a low- to medium-risk coronary artery bypass
      grafting, valve, and valve plus coronary artery bypass grafting population. These
      events might be targets for strategies aimed at quality improvement. METHODS: The
      present study was a retrospective cohort design performed at the Queen Elizabeth
      Health Science Centre. Low- to medium-risk patients who had experienced
      postoperative MACE were matched 1:1 with patients who had not experienced
      postoperative MACE. The operative notes, for both groups, were scored by 5
      surgeons to determine the frequency of 4 precursor events: bleeding, difficulty
      weaning from cardiopulmonary bypass, repair or regrafting, and incomplete
      revascularization or repair. A univariate comparison of >=1 precursor events in
      the matched groups was performed. RESULTS: A total of 311 MACE patients (98.4%)
      were matched. The primary outcome occurred more frequently in the MACE group than
      in the non-MACE group (33% vs 24%; P = .015). The incidence of the individual
      events of bleeding and difficulty weaning from cardiopulmonary bypass was
      significantly higher in the MACE group. Those patients with a precursor event in
      the absence of MACE also appeared to have a greater prevalence of other important
      postoperative outcomes. CONCLUSIONS: Patients undergoing cardiac surgery who are
      exposed to intraoperative precursor events were more likely to experience a
      postoperative MACE. Quality improvement techniques aimed at mitigating the
      consequences of precursor events might improve the surgical outcomes for cardiac
      surgical patients.

PMID- 23870158
TI  - Are discordant positron emission tomography and pathological assessments of the
      mediastinum in non-small cell lung cancer significant?
AB  - OBJECTIVE: Many patients with non-small cell lung cancer have positive
      mediastinal lymph nodes on preoperative positron emission tomography (PET) but do
      not have mediastinal involvement after surgery. The prognostic significance of
      this discordance was assessed. METHODS: This Institutional Review Board-approved
      study evaluated patients treated with upfront surgery at Duke Cancer Institute
      (Durham, NC) for non-small cell lung cancer from 1995 to 2008. Those staged with
      PET with pN0-1 disease after negative invasive mediastinal assessment were
      included. Mediastinal lymph nodes were scored as positive or negative based on
      visual analysis of the preoperative PET. Clinical outcomes of the PET-positive
      and PET-negative cohorts were estimated using the Kaplan-Meier method and
      compared using a log-rank test. Prognostic factors were assessed using a
      multivariate analysis. RESULTS: A total of 547 patients were assessed, of whom
      105 (19%) were PET positive in the mediastinum. The median number of mediastinal
      lymph node stations sampled was 4 (range, 1-9). The 5-year risk of local
      recurrence was 26% in PET-positive versus 21% in PET-negative patients (P = .50).
      Patterns of local failure were similar between the 2 groups. Distant recurrence
      (35% vs 29%; P = .63) and overall survival (44% vs 54%; P = .52) were comparable
      for PET-positive and PET-negative patients. On multivariate analysis, a positive
      PET was not significant for local recurrence (hazard ratio [HR], 1; P = 1),
      distant recurrence (HR, 0.82; P = .42), or overall survival (HR, 1.08; P = .62).
      CONCLUSIONS: Patients with positive mediastinal lymph nodes on preoperative PET,
      but negative on histologic analysis, are not at increased risk of disease
      recurrence. Pathologic staging remains the standard.

PMID- 23870159
TI  - The new St Jude Trifecta versus Carpentier-Edwards Perimount Magna and Magna Ease
      aortic bioprosthesis: is there a hemodynamic superiority?
AB  - OBJECTIVES: The Trifecta valve (St Jude Medical, St Paul, Minn) is a new
      bioprosthetic heart valve designed for supra-annular aortic valve replacement. We
      compared the hemodynamic performance of the Trifecta against the Perimount-Magna
      and Magna-Ease valve prostheses (Edwards Lifesciences, Irvine, Calif) in a
      nonrandomized, observational, single-center study. METHODS: A total of 346
      consecutive patients with aortic valve disease underwent aortic valve replacement
      between January 2003 and November 2011, with implantation of the Trifecta (group
      1, n = 121), the Perimount-Magna (group 2, n = 126), or the Magna Ease
      bioprosthesis (group 3, n = 99). Clinical and hemodynamic data were prospectively
      recorded and compared. Hemodynamic performance was evaluated by transthoracic
      echocardiography, including mean pressure gradient (MPG) and aortic valve area
      (AVA) at baseline, discharge, and 6-month follow-up. A multivariate model of
      covariance analysis was constructed to further compare the primary study end
      points of MPG and AVA at 6-month follow-up. RESULTS: For all valve sizes,
      unadjusted MPGs did not differ (P = .08), but AVAs differed (P < .001) between
      groups at 6-month follow-up. After final adjustment by a multivariate model of
      covariance analysis, neither the MPGs (P = .16) nor the AVAs (P = .92) at 6
      months postoperatively were influenced by the type of prosthesis used.
      CONCLUSIONS: The present observational study is the first to compare the new
      Trifecta valve with well-established supra-annular aortic valve bioprostheses
      from a hemodynamic perspective. Although mean pressure gradients and aortic valve
      areas seem to be advantageous at 6-month follow-up with the new Trifecta valve,
      after multivariate covariance analysis, no influence of prosthesis type on mean
      pressure gradient or aortic valve area could be demonstrated.

PMID- 23870161
TI  - Mechanisms of topical analgesics in relieving pain in an animal model of muscular
      inflammation.
AB  - OBJECTIVE: To investigate the possible mechanisms of topical analgesics in
      relieving pain in an animal model of muscular inflammation. METHODS: Adult
      Sprague-Dawley rats of both sexes were injected with complete Freund's adjuvant
      to induce inflammation in the anterior tibialis muscle of left hindlimb. One of
      two types of topical analgesics: Xiaotong Tiegao (XTT), a Tibetan herb compound,
      or Capzasin (CAP), a cream containing 0.1% capsaicin, was applied to the skin
      over the inflamed anterior tibialis muscle. The following experiments were
      performed: pain behavioral tests, evaluation of plasma extravasation in the
      affected limb, and electrophysiological recordings of afferent nerve fibers.
      RESULTS: The behavioral experiments demonstrated that applications of either type
      of topical analgesic to the skin over the inflamed muscle significantly reduced
      muscular inflammatory pain, as indicated by the increased weight bearing capacity
      on the affected hindlimb (with latencies of 10 minutes for XTT and 1-2 hours for
      CAP). Meanwhile, both analgesics caused plasma extravasation in the affected
      skin. Electrophysiological recordings from the afferent fibers in the related
      cutaneous nerve indicated that topical analgesics selectively activated C-fibers,
      but not A-fibers innervating the same region of receptive field. The latency and
      duration of C-fiber activation was similar to those of the reduction of muscular
      inflammatory pain. On the contrary, topical analgesics substantially decreased C
      fiber afferent spontaneous firing in the nerve innervating the inflamed muscle.
      Moreover, denervation of the affected skin blocked the analgesic effects of both
      topical analgesics in muscular inflammatory pain. CONCLUSION: This study suggests
      that topical analgesics may reduce the nociceptive input from inflamed muscles
      via a reflex mechanism by activating the cutaneous nociceptive afferents.

PMID- 23870160
TI  - Preoperative steroid treatment does not improve markers of inflammation after
      cardiac surgery in neonates: results from a randomized trial.
AB  - OBJECTIVE: Neonatal cardiac surgery requiring cardiopulmonary bypass results in a
      heightened inflammatory response. Perioperative glucocorticoid administration is
      commonly used in an attempt to reduce the inflammatory cascade, although
      characterization of the cytokine response to steroids in neonatal cardiac surgery
      remains elusive because of highly variable approaches in administration. This
      randomized trial was designed to prospectively evaluate the effect of specific
      glucocorticoid dosing protocols on inflammatory markers in neonatal cardiac
      surgery requiring cardiopulmonary bypass. METHODS: Neonates scheduled for cardiac
      surgery were randomly assigned to receive either 2-dose (8 hours preoperatively
      and operatively, n = 36) or single-dose (operatively, n = 32) methylprednisolone
      at 30 mg/kg per dose in a prospective double-blind trial. The primary outcome was
      the effect of these steroid regimens on markers of inflammation. Secondary
      analyses evaluated the association of specific cytokine profiles with
      postoperative clinical outcomes. RESULTS: Patient demographics, perioperative
      variables, and preoperative indices of inflammation were similar between the
      single- and 2-dose groups. Preoperative cytokine response after the 2-dose
      methylprednisolone protocol was consistent with an anti-inflammatory effect,
      although this did not persist into the postoperative period. Premedication
      baseline levels of interleukin-6, interleukin-8, interleukin-10, and tumor
      necrosis factor alpha were predictive of postoperative intensive care unit and
      hospital length of stay. Only interleukin-8 demonstrated a postoperative response
      associated with duration of intensive care unit and hospital stay. CONCLUSIONS:
      The addition of a preoperative dose of methylprednisolone to a standard
      intraoperative methylprednisolone dose does not improve markers of inflammation
      after neonatal cardiac surgery. The routine administration of preoperative
      glucocorticoids in neonatal cardiac surgery should be reconsidered.

PMID- 23870162
TI  - A novel subclass of bovine beta-defensins links reproduction and immunology.
AB  - beta-defensins are effector molecules of the innate immune system, found in many
      diverse species. Their presence in invertebrates as well as vertebrates suggests
      highly conserved functional roles. Most beta-defensins are believed to act as
      antimicrobial agents at epithelial surfaces, although additional functions have
      also been described, including immune regulatory activity, wound repair and a
      role in coat-colour determination. High expression of beta-defensins have been
      found in testis and epididymidal epithelium as well as in the seminal fluid of
      humans, macaque, rat, mouse and cow. Human and macaque beta-defensins have
      recently been shown to affect sperm motility while a mutation in beta-defensin
      126 is associated with reduced fertility in men. Genetic variation in bovine
      defensin genes may explain the increased incidence of low fertility in cattle.
      Here, we present a summary of the known functions of beta-defensins as well as
      their emerging role in reproduction and their potential to improve fertility in
      cattle. 

PMID- 23870163
TI  - A molecular study on bacterial resistance to arsenic-toxicity in surface and
      underground waters of Latium (Italy).
AB  - Latium, a region in central Italy, is known for its extensive volcanic areas that
      make a significant contribution to the arsenic (As) contamination of freshwater
      environments, even though some degree of As water pollution may be caused by
      human activities. The information available on indigenous As-resistant
      prokaryotes in aquatic environments of Latium is, however, still limited. In this
      study, we describe new bacteria that are resistant to arsenic toxicity and were
      isolated from the surface waters of Lake Vico and the Sacco River, two
      groundwater systems in Latium, as well as from bottled natural mineral water from
      the same region. The 16S rRNA gene sequence analysis for the As-resistant strains
      in lake and river waters points to a prevalence of beta- and gamma
      Proteobacteria, while alpha-Proteobacteria, Firmicutes and Bacteroidetes are
      represented to a lesser extent. By contrast, solely gamma-Proteobacteria were
      isolated from groundwater samples. The presence of Actinobacteria was documented
      exclusively in bottled mineral water. In addition, we conducted a DNA sequence
      based study on the gene codifying arsB, an As(III) efflux membrane protein pump
      related to arsenic resistance, for all the As-resistant bacterial isolates. A
      phylogenetic analysis was carried out on the newly sequenced 16S rRNA genes and
      arsB in the present study as well as on an additional 16S rRNA/arsB dataset we
      obtained previously from Lake Albano, from the Tiber and from a well in Bassano
      Romano located in Latium (Davolos and Pietrangeli, 2011). Overall, the
      phylogenetic diversity of As-resistant bacteria in underground water was very
      limited if compared with lentic and lotic waters. Lastly, our molecular data
      support the hypothesis that the horizontal gene transfer of ars in As-containing
      freshwater environments is not limited to closely-related genomes, but also
      occurs between bacteria that are distant from an evolutionary viewpoint, thereby
      indicating that such genetic events may be considered a source of microbial
      resistance to arsenic-toxicity. 

PMID- 23870164
TI  - Comparison of the Vitek 2 yeast susceptibility system with CLSI microdilution for
      antifungal susceptibility testing of fluconazole and voriconazole against Candida
      spp., using new clinical breakpoints and epidemiological cutoff values.
AB  - A commercially available, fully automated yeast susceptibility test system (Vitek
      2; bioMerieux, Marcy d'Etoile, France) was compared in 3 different laboratories
      with the Clinical and Laboratory Standards Institute (CLSI) reference
      microdilution (BMD) method by testing 2 quality control strains, 10
      reproducibility strains, and 425 isolates of Candida spp. against fluconazole and
      voriconazole. Reference CLSI BMD MIC endpoints and Vitek 2 MIC endpoints were
      read after 24 hours and 9.1-27.1 hours incubation, respectively. Excellent
      essential agreement (within 2 dilutions) between the reference and Vitek 2 MICs
      was observed for fluconazole (97.9%) and voriconazole (96.7%). Categorical
      agreement (CA) between the 2 methods was assessed using the new species-specific
      clinical breakpoints (CBPs): susceptible (S) <=2 MUg/mL, susceptible dose
      dependent (SDD) 4 MUg/mL, and resistant (R) >=8 MUg/mL for fluconazole and
      Candida albicans, Candida tropicalis, and Candida parapsilosis and <=32 MUg/mL
      (SDD), >=64 MUg/mL (R) for Candida glabrata; S <=0.12 MUg/mL, SDD 0.25-0.5
      MUg/mL, R >=1 MUg/mL for voriconazole and C. albicans, C. tropicalis, and C.
      parapsilosis, and <=0.5 MUg/mL (S), 1 MUg/mL (SDD), >=2 MUg/mL (R) for Candida
      krusei. The epidemiological cutoff value (ECV) of 0.5 MUg/mL for voriconazole and
      C. glabrata was used to differentiate wild-type (WT; MIC <= ECV) from non-WT (MIC
      > ECV) strains of this species. Due to the lack of CBPs for the less common
      species, the ECVs for fluconazole and voriconazole, respectively, were used for
      Candida lusitaniae (2 MUg/mL and 0.03 MUg/mL), Candida dubliniensis (0.5 MUg/mL
      and 0.03 MUg/mL), Candida guilliermondii (8 MUg/mL and 0.25 MUg/mL), and Candida
      pelliculosa (4 MUg/mL and 0.25 MUg/mL) to categorize isolates of these species as
      WT and non-WT. CA between the 2 methods was 96.8% for fluconazole and 96.5% for
      voriconazole with less than 1% very major errors and 1.3-3.0% major errors. The
      Vitek 2 yeast susceptibility system remains comparable to the CLSI BMD reference
      method for testing the susceptibility of Candida spp. when using the new (lower)
      CBPs and ECVs. 

PMID- 23870165
TI  - Leaks can dramatically decrease FiO2 on home ventilators: a bench study.
AB  - BACKGROUND: Long term oxygen therapy improves survival in hypoxemic patients with
      chronic obstructive pulmonary disease (COPD). Because pressure support
      ventilation with a home care ventilator is largely unsupervised, there is
      considerable risk of leakage occurring, which could affect delivered FiO2. We
      have therefore conducted a bench study in order to measure the effect of
      different levels of O2 supply and degrees of leakage on delivered FiO2.
      Ventilator tested: Legendair(r) (AiroxTM, Pau, France). Thirty-six measures were
      performed in each four ventilators with zero, 5 and 10 l.min-1 leakage and 1,2,4
      and 8 l O2 flow. FINDINGS: FiO2 decreased significantly with 5 l.min-1 leakage
      for all O2 flow rates, and with 10 l.min-1 at 4 and 8 l.min-1 O2. CONCLUSION:
      During application of NIV on home ventilators, leakage can dramatically decrease
      inspired FiO2 making it less effective. It is important to know the FiO2
      dispensed when NIV is used for COPD at home. We would encourage industry to
      develop methods for FiO2 regulation Chronic use of NIV for COPD with controlled
      FiO2 or SpO2 requires further studys.

PMID- 23870166
TI  - Incidence of pertussis in patients of general practitioners in Poland.
AB  - We estimated the incidence of pertussis in patients consulting general
      practitioners (GPs). Between July 2009 and April 2011, we conducted a prospective
      cohort study of patients attending 78 general practices (158 863 persons
      overall). We included patients aged >= 3 years, with cough lasting 2-15 weeks,
      who gave informed consent. GPs interviewed eligible patients, collected a blood
      specimen, and a nasopharyngeal swab. At follow-up 30-60 days after the initial
      visit, physicians collected a second blood specimen and conducted patient
      interview. Cases were confirmed by specific IgA and/or IgG antibody titre
      exceeding significantly the general population background level or detection of
      bacterial DNA by real-time PCR. During the study period, 3864 patients with
      prolonged cough consulted the participating GPs, of those 1852 met the inclusion
      criteria, 1232 were recruited, and 288 were confirmed as pertussis cases (4% by
      PCR, 96% by serology). The adjusted incidence rate was 201.1/100 000 person-years
      [95% confidence interval (CI) 133.9-302.0], ranging from 456.5 (95% CI 239.3
      870.8) in the 15-19 years group to 94.0 (95% CI 33.4-264.5) in the 25-29 years
      group. The reporting ratio was 61, ranging from 4 in those aged 3-5 years, to 167
      in those aged 65-69 years. The study confirmed high incidence of pertussis in all
      age groups in the general population, in particular in adults, not appropriately
      documented by the existing surveillance system.

PMID- 23870167
TI  - Empirical assessment of competitive hybridization and noise in ultra high density
      canine tiling arrays.
AB  - BACKGROUND: In addition to probe sequence characteristics, noise in hybridization
      array data is thought to be influenced by competitive hybridization between
      probes tiled at high densities. Empirical evaluation of competitive hybridization
      and an estimation of what other non-sequence related features might affect noisy
      data is currently lacking. RESULTS: A high density array was designed to a 1.5
      megabase region of the canine genome to explore the potential for probe
      competition to introduce noise. Multivariate assessment of the influence of
      probe, segment and design characteristics on hybridization intensity demonstrate
      that whilst increased density significantly depresses fluorescence intensities,
      this effect is largely consistent when an ultra high density offset is applied.
      Signal variation not attributable to sequence composition resulted from the
      reduction in competition when large inter-probe spacing was introduced due to
      long repetitive elements and when a lower density offset was applied. Tiling of
      probes immediately adjacent to various classes of repeat elements did not
      generate noise. Comparison of identical probe sets hybridized with DNA extracted
      from blood or saliva establishes salivary DNA as a source of noise. CONCLUSIONS:
      This analysis demonstrates the occurrence of competitive hybridization between
      oligonucleotide probes in high density tiling arrays. It supports that probe
      competition does not generate random noise when it is maintained across a region.
      To prevent the introduction of noise from this source, the degree of competition
      should be regulated by minimizing variation in density across the target region.
      This finding can make an important contribution to optimizing coverage whilst
      minimizing sources of noise in the design of high density tiling arrays.

PMID- 23870168
TI  - The promoter of miR-663 is hypermethylated in Chinese pediatric acute myeloid
      leukemia (AML).
AB  - BACKGROUND: There is growing evidence supporting a role for microRNAs (miRNA) as
      targets in aberrant mechanisms of DNA hypermethylation. Epigenetic silencing of
      tumor suppressor miRNAs, including miR-663, which has recently been reported to
      be inactivated by hypermethylation in several cancers, may play important roles
      in pediatric acute myeloid leukemia (AML). However, expression of miR-663 and its
      promoter methylation remain status unclear in childhood leukemia. METHODS:
      Promoter methylation status of miR-663 was investigated by methylation specific
      PCR (MSP) and bisulfate genomic sequencing (BGS). Transcriptional expression of
      miR-663 was evaluated by semi-quantitative and real-time PCR, and the
      relationship between expression of miR-663 and promoter methylation was confirmed
      using 5-aza-2'-deoxycytidine (5-Aza) demethylation reagent. RESULTS: MiR-663 was
      aberrantly methylated in 45.5% (5/11) leukemia cell lines; BGS showed that the
      promoter was significantly methylated in three AML cell lines; methylation of miR
      663 was significantly higher in Chinese pediatric AML patients [41.4% (29/70)]
      compared to normal bone marrow (NBM) control samples [10.0% (3/30)]. These
      results were confirmed by both BGS and 5-Aza demethylation analysis. In addition,
      miR-663 transcript expression was significantly lower in AML patients, both with
      and without miR-663 methylation, compared to controls; however, there were no
      significant differences in clinical features or French-American-British (FAB)
      classification between patients with and without miR-663 methylation.
      CONCLUSIONS: Expression of miR-663 was significantly lower in pediatric AML cells
      compared to NBM controls; furthermore, a high frequency of miR-663 promoter
      hypermethylation was observed in both AML cell lines and pediatric AML samples.
      Inactivation of miR-663 by promoter hypermethylation could be affected by 5-Aza
      demethylation. These findings suggest that hypermethylation of the miR-663
      promoter may be an early event in the development of pediatric AML.

PMID- 23870171
TI  - The aluminium content of breast tissue taken from women with breast cancer.
AB  - The aetiology of breast cancer is multifactorial. While there are known genetic
      predispositions to the disease it is probable that environmental factors are also
      involved. Recent research has demonstrated a regionally specific distribution of
      aluminium in breast tissue mastectomies while other work has suggested mechanisms
      whereby breast tissue aluminium might contribute towards the aetiology of breast
      cancer. We have looked to develop microwave digestion combined with a new form of
      graphite furnace atomic absorption spectrometry as a precise, accurate and
      reproducible method for the measurement of aluminium in breast tissue biopsies.
      We have used this method to test the thesis that there is a regional distribution
      of aluminium across the breast in women with breast cancer. Microwave digestion
      of whole breast tissue samples resulted in clear homogenous digests perfectly
      suitable for the determination of aluminium by graphite furnace atomic absorption
      spectrometry. The instrument detection limit for the method was 0.48 MUg/L.
      Method blanks were used to estimate background levels of contamination of 14.80
      MUg/L. The mean concentration of aluminium across all tissues was 0.39 MUg Al/g
      tissue dry wt. There were no statistically significant regionally specific
      differences in the content of aluminium. We have developed a robust method for
      the precise and accurate measurement of aluminium in human breast tissue. There
      are very few such data currently available in the scientific literature and they
      will add substantially to our understanding of any putative role of aluminium in
      breast cancer. While we did not observe any statistically significant differences
      in aluminium content across the breast it has to be emphasised that herein we
      measured whole breast tissue and not defatted tissue where such a distribution
      was previously noted. We are very confident that the method developed herein
      could now be used to provide accurate and reproducible data on the aluminium
      content in defatted tissue and oil from such tissues and thereby contribute
      towards our knowledge on aluminium and any role in breast cancer.

PMID- 23870169
TI  - Integration-deficient lentivectors: an effective strategy to purify and
      differentiate human embryonic stem cell-derived hepatic progenitors.
AB  - BACKGROUND: Human pluripotent stem cells (hPSCs) hold great promise for
      applications in regenerative medicine. However, the safety of cell therapy using
      differentiated hPSC derivatives must be improved through methods that will permit
      the transplantation of homogenous populations of a specific cell type. To date,
      purification of progenitors and mature cells generated from either embryonic or
      induced pluripotent stem cells remains challenging with use of conventional
      methods. RESULTS: We used lentivectors encoding green fluorescent protein (GFP)
      driven by the liver-specific apoliprotein A-II (APOA-II) promoter to purify human
      hepatic progenitors. We evaluated both integrating and integration-defective
      lentivectors in combination with an HIV integrase inhibitor. A human embryonic
      stem cell line was differentiated into hepatic progenitors using a chemically
      defined protocol. Subsequently, cells were transduced and sorted at day 16 of
      differentiation to obtain a cell population enriched in hepatic progenitor cells.
      After sorting, more than 99% of these APOA-II-GFP-positive cells expressed
      hepatoblast markers such as alpha-fetoprotein and cytokeratin 19. When further
      cultured for 16 days, these cells underwent differentiation into more mature
      cells and exhibited hepatocyte properties such as albumin secretion. Moreover,
      they were devoid of vector DNA integration. CONCLUSIONS: We have developed an
      effective strategy to purify human hepatic cells from cultures of differentiating
      hPSCs, producing a novel tool that could be used not only for cell therapy but
      also for in vitro applications such as drug screening. The present strategy
      should also be suitable for the purification of a broad range of cell types
      derived from either pluripotent or adult stem cells.

PMID- 23870172
TI  - jSIPRO - analysis tool for magnetic resonance spectroscopic imaging.
AB  - Magnetic resonance spectroscopic imaging (MRSI) involves a huge number of spectra
      to be processed and analyzed. Several tools enabling MRSI data processing have
      been developed and widely used. However, the processing programs primarily focus
      on sophisticated spectra processing and offer limited support for the analysis of
      the calculated spectroscopic maps. In this paper the jSIPRO (java Spectroscopic
      Imaging PROcessing) program is presented, which is a java-based graphical
      interface enabling post-processing, viewing, analysis and result reporting of
      MRSI data. Interactive graphical processing as well as protocol controlled batch
      processing are available in jSIPRO. jSIPRO does not contain a built-in fitting
      program. Instead, it makes use of fitting programs from third parties and manages
      the data flows. Currently, automatic spectra processing using LCModel, TARQUIN
      and jMRUI programs are supported. Concentration and error values, fitted spectra,
      metabolite images and various parametric maps can be viewed for each calculated
      dataset. Metabolite images can be exported in the DICOM format either for
      archiving purposes or for the use in neurosurgery navigation systems. 

PMID- 23870173
TI  - Structural identifiability analyses of candidate models for in vitro Pitavastatin
      hepatic uptake.
AB  - In this paper a review of the application of four different techniques (a version
      of the similarity transformation approach for autonomous uncontrolled systems, a
      non-differential input/output observable normal form approach, the characteristic
      set differential algebra and a recent algebraic input/output relationship
      approach) to determine the structural identifiability of certain in vitro
      nonlinear pharmacokinetic models is provided. The Organic Anion Transporting
      Polypeptide (OATP) substrate, Pitavastatin, is used as a probe on freshly
      isolated animal and human hepatocytes. Candidate pharmacokinetic non-linear
      compartmental models have been derived to characterise the uptake process of
      Pitavastatin. As a prerequisite to parameter estimation, structural
      identifiability analyses are performed to establish that all unknown parameters
      can be identified from the experimental observations available. 

PMID- 23870174
TI  - Argan oil prevents prothrombotic complications by lowering lipid levels and
      platelet aggregation, enhancing oxidative status in dyslipidemic patients from
      the area of Rabat (Morocco).
AB  - BACKGROUND: It is now established that patients with hyperlipidemia have a high
      risk of atherosclerosis and thrombotic complications, which are two important
      events responsible for the onset and progression of cardiovascular disease. In
      the context of managing dyslipidemia by means of dietary advice based on the
      consumption of argan oil, we wanted to investigate the effect of virgin argan oil
      on plasma lipids, and for the first time, on the platelet hyperactivation and
      oxidative status associated with dyslipidemia. This study concerns patients
      recruited in the area of Rabat in Morocco. METHODS: 39 dyslipidemic (79% women)
      patients were recruited for our study in the area of Rabat in Morocco. They were
      randomly assigned to the two following groups: the argan group, in which the
      subjects consumed 25 mL/day of argan oil at breakfast for 3 weeks, and the
      control group in which argan oil was replaced by butter. RESULTS: After a 3-week
      consumption period, blood total cholesterol was significantly lower in the argan
      oil group, as was LDL cholesterol (23.8% and 25.6% lower, respectively). However,
      the HDL cholesterol level had increased by 26% at the end of the intervention
      period compared to baseline. Interestingly, in the argan oil group thrombin
      induced platelet aggregation was lower, and oxidative status was enhanced as a
      result of lower platelet MDA and higher GPx activity, respectively. CONCLUSIONS:
      In conclusion, our results, even if it is not representative of the Moroccan
      population, show that argan oil can prevent the prothrombotic complications
      associated with dyslipidemia, which are a major risk factor for cardiovascular
      disease.

PMID- 23870176
TI  - Introduction to the NeuroImage special issue "Mapping the Connectome".

PMID- 23870175
TI  - Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in
      vitro.
AB  - BACKGROUND: Propolis is a resin collected by bees from plant buds and exudates,
      which is further processed through the activity of bee enzymes. Propolis has been
      shown to possess many biological and pharmacological properties, such as
      antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this
      bioactivity profile, this resin can become an alternative, economic and safe
      source of natural bioactive compounds.Antitumor action has been reported in vitro
      and in vivo for propolis extracts or its isolated compounds; however, Portuguese
      propolis has been little explored. The aim of this work was to evaluate the in
      vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell
      line HCT-15, assessing the effect of different fractions (hexane, chloroform and
      ethanol residual) of a propolis ethanol extract on cell viability, proliferation,
      metabolism and death. METHODS: Propolis from Angra do Heroismo (Azores) was
      extracted with ethanol and sequentially fractionated in solvents with increasing
      polarity, n-hexane and chloroform. To assess cell viability, cell proliferation
      and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium
      iodide were used, respectively. Glycolytic metabolism was estimated using
      specific kits. RESULTS: All propolis samples exhibited a cytotoxic effect against
      tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most
      enriched in phenolic compounds, appears to be the most active, both in terms of
      inhibition of viability and cell death. Data also show that this cytotoxicity
      involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in
      glucose consumption and lactate production. CONCLUSION: Our results show that
      Portuguese propolis from Angra do Heroismo (Azores) can be a potential
      therapeutic agent against human colorectal cancer.

PMID- 23870177
TI  - Associations between social support and stroke survivors' health-related quality
      of life--a systematic review.
AB  - OBJECTIVE: Social support to stroke survivors has been recognized as an important
      determinant of their health-related quality of life (HRQoL), but this
      relationship is not clarified to date. More insight in the relationships between
      various types (i.e. emotional, instrumental, or informational support) and
      sources (i.e. partner, children) of social support and HRQoL might target post
      stroke educational and counseling interventions to strengthen patient's social
      networks and supportive relationships. METHODS: Systematic review. RESULTS: 11
      original articles could be included. Most of these articles studied the overall
      perceived social support without further specification of type or source. They
      show a positive relation between perceived social support and stroke survivors'
      HRQoL. Relations between perceived social support and HRQoL seems to be more
      often significant and were stronger than relationships between specific social
      support types or sources and HRQoL. CONCLUSION: Due to the small number of
      studies and the heterogeneity in methods of assessing social support, a clear
      statement about the specific influence of social support source or type could not
      be made. PRACTICE IMPLICATIONS: Attention should be paid to promoting social
      support on the short and long term. Further research is needed to clarify the
      influence of social support type and source.

PMID- 23870178
TI  - Correlation of echocardiographic left atrial abnormality with myocardial ischemia
      during myocardial perfusion assessment in the presence of known left ventricular
      hypertrophy.
AB  - Left atrial (LA) abnormality, an easily quantifiable parameter of left
      ventricular (LV) diastolic dysfunction, has been associated with cardiovascular
      risk similar to that of LV hypertrophy. The correlation between LV hypertrophy
      and LA abnormality among patients undergoing myocardial perfusion (MP) study has
      not been described. We prospectively studied 78 consecutive patients with LV
      hypertrophy who underwent MP study after screening for electrocardiographic and
      echocardiographic LA abnormality over a 6-month period. Of those, 48 had a
      positive MP imaging result, and 30 did not. LA size (p = 0.002) and P-wave
      duration (p = 0.017) were significantly increased in the former. The differential
      change in LA size (no defect = 35 +/- 4, mild = 36 +/- 5, moderate = 38 +/- 5,
      severe = 44 +/- 5 mm; p <0.0001) and P-wave duration (no defect = 107 +/- 14,
      mild = 110 +/- 17, moderate = 113 +/- 15, severe = 127 +/- 22 ms; p = 0.003) was
      greatest when the MP study defect exceeded moderate severity. In conclusion, the
      presence of LA abnormality could assist during MP study interpretation among
      patients with LV hypertrophy when such markers appear to be correlated with the
      severity of the MP study defect.

PMID- 23870179
TI  - The ever expanding spectrum of phenotypic diversity in hypertrophic
      cardiomyopathy.

PMID- 23870180
TI  - Frequency of Takotsubo cardiomyopathy in postmenopausal women presenting with an
      acute coronary syndrome: still underdiagnosed.

PMID- 23870181
TI  - Relation of triiodothyronine to subclinical myocardial injury in patients with
      chest pain.

PMID- 23870183
TI  - Effects of intrathecal opioid administration on pituitary function.
AB  - OBJECTIVE: To report a case of panhypopituitarism in a patient receiving long
      term intrathecal opioids. DESIGN: This is a case study and review of current
      medical literature. There is a 7-year follow-up time. PATIENTS: One adult male
      clinic patient with pituitary dysfunction. MAIN OUTCOME MEASURE(S): Intrathecal
      opioids may lead to pituitary dysfunction. RESULTS: Intrathecal opioid pain
      management may produce some generalized effects, as well as pituitary
      hypofunction, as evidenced by this case. This patient experienced simultaneous
      suppression of multiple anterior pituitary hormones, which persisted with chronic
      oral opioid therapy following cessation of an intrathecal opioid pump.
      CONCLUSIONS: All hypothalamic pituitary axes, seem potentially vulnerable to
      therapy with intrathecal opioids. When patients are receiving these medications,
      symptoms need to be critically evaluated with appropriate laboratory assessments
      for suspected pituitary dysfunction. Further studies are required in order to
      create formal recommendations for routine patient surveillance during intrathecal
      opioid therapy.

PMID- 23870182
TI  - Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for
      the early detection of lung cancer in the post-National Lung Screening Trial era.
AB  - Lung cancer is the leading cause of cancer death worldwide in part due to our
      inability to identify which smokers are at highest risk and the lack of effective
      tools to detect the disease at its earliest and potentially curable stage. Recent
      results from the National Lung Screening Trial have shown that annual screening
      of high-risk smokers with low-dose helical computed tomography of the chest can
      reduce lung cancer mortality. However, molecular biomarkers are needed to
      identify which current and former smokers would benefit most from annual computed
      tomography scan screening in order to reduce the costs and morbidity associated
      with this procedure. Additionally, there is an urgent clinical need to develop
      biomarkers that can distinguish benign from malignant lesions found on computed
      tomography of the chest given its very high false positive rate. This review
      highlights recent genetic, transcriptomic and epigenomic biomarkers that are
      emerging as tools for the early detection of lung cancer both in the diagnostic
      and screening setting. 

PMID- 23870184
TI  - Osur et al.'s Implementation of misoprostol for postabortion care in Kenya and
      Uganda: a qualitative evaluation.

PMID- 23870185
TI  - Letter to the editor.

PMID- 23870186
TI  - Sperm banking for fertility preservation: a 20-year experience.
AB  - OBJECTIVE: Sperm banking is an effective method to preserve fertility, but is not
      universally offered to males facing gonadotoxic treatment in the United States.
      We compared the disposition and semen parameters of cryopreserved sperm from
      individuals referred for sperm banking secondary to a cancer diagnosis to those
      of sperm from men banking for infertility reasons. STUDY DESIGN: We performed a
      retrospective cohort study that reviewed 1118 records from males who presented to
      bank sperm at Washington University between 1991 and 2010. We collected and
      analyzed demographics, semen parameters, and disposition of banked sperm.
      RESULTS: Four hundred and twenty-three men with cancer and 348 banking for
      infertility reasons attempted sperm cryopreservation in our unit during the
      specified time period. The most prevalent cancers in our cohort were testicular
      (32%), lymphoma (25%), and leukemia (11%). Patients with leukemia had the lowest
      pre-thaw counts and motility. Most cancer patients (57%) who banked elected to
      use, transfer to another facility, or keep their specimens in storage. The
      remaining samples were discarded electively (34%) or following death (8%).
      Overall semen parameters were similar between the cancer and infertility groups,
      but demographics, ability to bank a sample, azoospermia rates, length of storage,
      current banking status, and use of banked sperm differed significantly between
      the two groups. CONCLUSIONS: The majority of cancer patients who banked survived
      their cancer and chose to continue storage of banked samples. Cancer patients
      were more likely than infertility patients to use or continue storage of banked
      samples. Our study provides evidence that sperm banking is a utilized modality of
      fertility preservation in patients with a myriad of cancer diagnoses and should
      be offered to all men facing gonadotoxic therapies. Further work is needed to
      determine where disparities in access to sperm banking exist to improve the
      potential for future fertility in these males.

PMID- 23870187
TI  - Predictors of fertility quality of life (FertiQoL) in infertile women: analysis
      of confounding factors.
AB  - OBJECTIVE: Infertility may adversely influence quality of life (QoL). The aim of
      this study was to compare QoL in women with primary and secondary infertility,
      and identify factors associated with poor and good QoL. STUDY DESIGN: Quality of
      life was measured using the FertiQoL tool in 273 patients attending an
      infertility clinic, and demographic and clinical characteristics of the patients
      were recorded. Patients with primary and secondary infertility were compared for
      QoL subscales, and other confounding factors were investigated using multiple
      regression analysis. RESULTS: Women with secondary infertility obtained higher
      scores in emotional, mind/body, and social domains of the core subscale,
      tolerability domain of the treatment subscale, and total QoL (p<0.05). Women
      desiring psychological support showed lower scores in all domains except
      environment. Prolonged duration of infertility was associated with lower scores
      of mind/body, social, tolerability domains and total QoL score (p<0.05). Multiple
      regression analysis showed that the status of education and secondary infertility
      had a positive impact, whereas prolonged duration of infertility and desire for
      psychological support had a negative impact on total QoL scores. CONCLUSION: QoL
      scores were better in patients with secondary infertility and higher educational
      status, whereas scores were negatively affected by prolonged duration of
      infertility and desire for psychological support.

PMID- 23870188
TI  - Foley catheter or prostaglandin E2 inserts for induction of labour at term: an
      open-label randomized controlled trial (PROBAAT-P trial) and systematic review of
      literature.
AB  - OBJECTIVE: To assess the safety and effectiveness of a transcervical Foley
      catheter compared to vaginal prostaglandin E2 inserts for term induction of
      labour. STUDY DESIGN: We conducted an open-label randomized controlled trial in
      five hospitals in the Netherlands. Women with a singleton term pregnancy in
      cephalic presentation, intact membranes, unfavourable cervix, and no prior
      caesarean section were enrolled. Participants were randomly allocated by a web
      based randomization system to induction of labour with a 30 ml Foley catheter or
      10mg slow-release vaginal prostaglandin E2 inserts in a 1:1 ratio. Due to the
      nature of the intervention this study was not blinded. The primary outcome was
      the caesarean section rate. Secondary outcomes were maternal and neonatal
      morbidity and time from intervention to birth. Additionally, we carried out a
      systematic review and meta-analysis of similar studies. RESULTS: We analyzed 226
      women: 107 received a Foley catheter and 119 inserts. Caesarean section rates
      were comparable (20% versus 22%, RR 0.90, 95% CI 0.54-1.50). Secondary outcomes
      showed no differences. We observed no serious maternal or neonatal morbidity.
      Meta-analysis showed comparable caesarean section rates, but significantly fewer
      cases of hyperstimulation during the ripening phase when a Foley catheter was
      used. CONCLUSIONS: We found, in this relatively small study, no differences in
      effectiveness and safety of induction of labour with a Foley catheter and 10mg
      slow release vaginal prostaglandin E2 inserts. Meta-analysis confirmed a
      comparable caesarean section rate, and showed fewer cases of hyperstimulation
      when a Foley catheter was used.

PMID- 23870189
TI  - Effects of the addition of low-dose ketamine to propofol-fentanyl anaesthesia
      during diagnostic gynaecological laparoscopy.
AB  - OBJECTIVES: Diagnostic gynaecological laparoscopy (DGL) is a brief procedure,
      generally performed on an outpatient basis. Propofol-fentanyl is often used for
      anaesthesia in minor outpatient procedures because of its rapid onset, short
      duration of action and smooth patient awakening. However, propofol has various
      cardiovascular effects such as reduced arterial pressure, cardiac output and
      cardiac index. Ketamine is an intravenous anaesthetic and short-acting analgesic
      that could alleviate the haemodynamic effects of propofol due to its
      sympathomimetic activity. The aim of this placebo-controlled trial was to
      evaluate the effects of the addition of low-dose ketamine to propofol-fentanyl
      anaesthesia in DGL. STUDY DESIGN: In this double-blind randomized trial, 60
      healthy women undergoing gynaecological laparoscopy to investigate infertility
      were studied. Following injection of midazolam and fentanyl in all patients, the
      study group (n=30) received ketamine 0.5 mg/kg and propofol 1-2.5 mg/kg, and the
      placebo group (n=30) received saline 0.9% and propofol 1-2.5 mg/kg. Propofol was
      subsequently infused for the maintenance of anaesthesia. RESULTS: Patients in the
      study group had a significantly lower incidence of pain than patients in the
      placebo group during propofol injection (13% vs 87%, respectively; p<0.0001).
      After induction of anaesthesia, 16 (53%) patients in the placebo group and three
      (10%) patients in the study group had a decreased heart rate (p<0.001). The
      decrease in mean arterial pressure was greater in the placebo group compared with
      the study group (37% vs 7%, respectively; p<0.001). During the procedure, the
      total mean+/-standard deviation dose of propofol was 420+/-65 mg in the placebo
      group and 330+/-35 mg in the study group (p<0.001). Pain scores for the first 3h
      after the operation were significantly lower in the study group (p<0.001).
      CONCLUSION: Use of low-dose ketamine with propofol-fentanyl anaesthesia in
      patients undergoing DGL was associated with less pain during propofol injection,
      lower incidence of haemodynamic changes, lower total dose of propofol and
      improved postoperative analgesia.

PMID- 23870190
TI  - The involvement of osteopontin and beta3 integrin in implantation and endometrial
      receptivity in an early mouse pregnancy model.
AB  - OBJECTIVE: To explore the roles of osteopontin and beta3 integrin in successful
      implantation. STUDY DESIGN: In this study, an early pregnant mouse model was
      established by peritoneal injection of pregnant mare serum gonadotropin and human
      chorionic gonadotropin (PMSG+hCG). The expression of osteopontin (OPN) and beta3
      integrin on the endometrium was measured by immunohistochemistry, RT-PCR, and
      western blot. The function of OPN and beta3 integrin in implantation was
      investigated by intrauterine injection of OPN and beta3 integrin antibody.
      RESULTS: We found that PMSG+hCG injection significantly increased the number of
      blastocysts during implantation as well as the concentration of estradiol and
      progesterone in serum and endometrium tissues. OPN and beta3 integrin were co
      expressed in luminal epithelium and their levels dynamically changed from day 4
      to day 8 of pregnancy with peak expression on day 5. The percentages of OPN and
      beta3 integrin positive cells in the luminal epithelium were significantly higher
      in PMSG+hCG-stimulated mice on day 5 than in control mice. Functional blockade of
      OPN and beta3 integrin significantly inhibited implantation. CONCLUSIONS: This
      study suggests that co-expression of OPN and beta3 integrin is a biological
      marker for good endometrial receptivity and that both proteins play a crucial
      role in blastocyst implantation.

PMID- 23870191
TI  - Automatic landmark annotation and dense correspondence registration for 3D human
      facial images.
AB  - BACKGROUND: Traditional anthropometric studies of human face rely on manual
      measurements of simple features, which are labor intensive and lack of full
      comprehensive inference. Dense surface registration of three-dimensional (3D)
      human facial images holds great potential for high throughput quantitative
      analyses of complex facial traits. However there is a lack of automatic high
      density registration method for 3D faical images. Furthermore, current approaches
      of landmark recognition require further improvement in accuracy to support
      anthropometric applications. RESULT: Here we describe a novel non-rigid
      registration method for fully automatic 3D facial image mapping. This method
      comprises two steps: first, seventeen facial landmarks are automatically
      annotated, mainly via PCA-based feature recognition following 3D-to-2D data
      transformation. Second, an efficient thin-plate spline (TPS) protocol is used to
      establish the dense anatomical correspondence between facial images, under the
      guidance of the predefined landmarks. We demonstrate that this method is highly
      accurate in landmark recognition, with an average RMS error of ~1.7 mm. The
      registration process is highly robust, even for different ethnicities.
      CONCLUSION: This method supports fully automatic registration of dense 3D facial
      images, with 17 landmarks annotated at greatly improved accuracy. A stand-alone
      software has been implemented to assist high-throughput high-content
      anthropometric analysis.

PMID- 23870192
TI  - Effects of metformin on fertilisation of bovine oocytes and early embryo
      development: possible involvement of AMPK3-mediated TSC2 activation.
AB  - Studies on bovine oocytes have revealed that the activation of adenosine
      monophosphate activated protein kinase (AMPK) by millimolar concentrations of
      metformin controls nuclear maturation. Tuberous sclerosis complex 2 (TSC2) has
      been identified as a downstream target of AMPK. The objective of this study was
      to investigate the effects of addition of low concentrations of metformin (1 nM
      to 10 MUM) on the percentage of cultured cumulus-oocyte complexes (COC) giving
      rise to cleavage-stage embryos and AMPK-mediated TSC2 activation. Metformin was
      supplemented either throughout in vitro embryo production (IVP) or only during in
      vitro fertilization (IVF). COC were matured in vitro, inseminated, and
      presumptive zygotes cultured for a further 72 h post insemination before the
      percentage of COC that gave rise to zygotes and early embryo development was
      assessed. The presence of TSC2 in bovine embryos and its possible AMPK-induced
      activation were assessed by immunocytochemistry. Metformin had a dose-dependent
      effect on the numbers of cultured COC that gave rise to embryos. Drug treatment
      either throughout IVP or only during IVF decreased the percentage of >= 8-cell
      embryos (1 MUM, P < 0.05; 10 MUM, P < 0.01; and 0.1 MUM, 10 MUM, P < 0.01,
      respectively) and increased the percentage of 2-cell embryos (10 MUM, P < 0.01
      and P < 0.05 respectively). The percentage of cultured COC that gave rise to
      zygotes was not affected by metformin. TSC2 is expressed in early embryos.
      Metformin (10 MUM) either throughout IVP or during IVF only, increased AMPK
      induced PhosphoS1387-TSC2 immunoreactivity (P < 0.01) and this increase
      corresponded to the total TSC2 protein levels expressed in cells. Our results
      suggest that there is a dose-dependent negative effect of metformin on the
      ability of oocytes to cleave following insemination, possibly mediated through an
      AMPK-induced activation of TSC2.

PMID- 23870193
TI  - Nervonic acid is much lower in donor milk than in milk from mothers delivering
      premature infants--of neglected importance?
AB  - Nervonic acid is important for white matter development and its incorporation
      increases rapidly in the last trimester, but few studies focus on this fatty
      acid. Other mother's milk, usually after term delivery, is often used for
      premature infants, whose mothers cannot breastfeed. The fatty acid (FA)
      concentrations were analyzed by gas chromatography in 12 samples of donor human
      milk (DHM) from five mothers, and compared to milk from 42 mothers delivering
      preterm infants. Fat, lactose and protein contents were compared. Nervonic acid
      showed sevenfold higher concentrations and LCPUFA 90% higher concentrations in
      premature milk compared to DHM. Linoleic acid was found in 43% higher
      concentrations in DHM than in premature milk. The fat and protein contents were
      lower in DHM. Our results suggest that studies are warranted to investigate if
      DHM given to premature infants may require supplementation of nervonic acid, and
      not only LCPUFA, protein and minerals. 

PMID- 23870194
TI  - High capacity for leukotriene biosynthesis in peripheral blood during pregnancy.
AB  - Pregnancy is accompanied by major immunological changes to maintain both
      tolerance for the fetus and immune competence. Leukotrienes are powerful 5
      lipoxygenase-derived inflammatory mediators and the characteristics of
      leukotriene-related diseases (e.g., asthma, allergic rhinitis) change during
      pregnancy. Here, we show that pregnancy affects leukotriene synthesis in human
      blood and leukocytes. 5-Lipoxygenase product formation in stimulated blood of
      pregnant women was significantly higher than in non-pregnant females. Although a
      pregnancy-related increase in neutrophil and monocyte counts may explain these
      observations, granulocytes of pregnant donors have lower leukotriene-synthetic
      capacities. On the other hand, granulocytes from non-pregnant woman produced more
      leukotrienes when resuspended in plasma of pregnant women than of non-pregnant
      females. Together, we show that leukotriene biosynthesis in maternal blood is
      increased by the interrelations of higher leukocyte numbers, lower cellular
      capacity for leukotriene synthesis and stimulatory effects of plasma. This bias
      may affect leukotriene-related diseases during pregnancy and their
      pharmacological treatment. 

PMID- 23870196
TI  - Factors for hepatitis B vaccination and abnormal liver function in Chinese
      patients with inflammatory bowel disease: a single center experience.
AB  - OBJECTIVES: We aimed to determine the prevalence of chronic and past hepatitis B
      virus (HBV) infection in Chinese patients with inflammatory bowel disease (IBD),
      and to determine the risk factors associated with having received no vaccination
      for HBV and abnormal liver function among our patients. METHODS: The prevalence
      of chronic or past infection with HBV infection and effective HBV vaccination
      were determined in patients with IBD who attended the IBD Clinic of the Queen
      Mary Hospital in Hong Kong, China. Risk factors associated with the absence of
      HBV vaccination and abnormal liver function were identified. RESULTS: A total of
      267 Chinese IBD patients (166 ulcerative colitis and 101 Crohn's disease) were
      enrolled. The mean follow-up period was 10.5 years. Chronic and past HBV
      infection was detected in 6.7% and 28.5% patients, respectively. Altogether 102
      patients lacked effective HBV vaccination. Multivariate analysis found that elder
      age at diagnosis of IBD (OR 1.02, 95% CI 1.00-0.94) and the absence of using
      thiopurine (OR 0.53, 95% CI 0.29-0.94) were associated with the presence of anti
      HBs. Abnormal liver function was detected in 27 (10.1%) patients. The use of anti
      tumor necrosis factor agents (OR 4.6, 95% CI 1.3-16.0), previous bowel resection
      (OR 3.7, 95% CI 1.5-9.2) and male gender (OR 4.4, 95% CI 1.4-13.7) were
      significant risk factors for abnormal liver function. CONCLUSIONS: The use of
      thiopurine and younger age at diagnosis were associated with no vaccination
      against HBV in Chinese IBD patients. Chronic or past HBV infection was, however,
      not associated with abnormal liver function in these patients.

PMID- 23870195
TI  - Genetics of coronary artery calcification among African Americans, a meta
      analysis.
AB  - BACKGROUND: Coronary heart disease (CHD) is the major cause of death in the
      United States. Coronary artery calcification (CAC) scores are independent
      predictors of CHD. African Americans (AA) have higher rates of CHD but are less
      well-studied in genomic studies. We assembled the largest AA data resource
      currently available with measured CAC to identify associated genetic variants.
      METHODS: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association
      with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse
      variance weighted meta-analysis on results for 5,823 AA from 8 studies.
      Heritability was calculated using family studies. The most significant SNPs among
      AAs were evaluated in European Ancestry (EA) CAC data; conversely, the
      significance of published SNPs for CAC/CHD in EA was queried within our AA meta
      analysis. RESULTS: Heritability of CAC was lower in AA (~30%) than previously
      reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of
      67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data.
      Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA
      reached nominal significance for CAC in AA, with concordant direction. Among AA,
      rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region.
      CONCLUSIONS: While we observed substantial heritability for CAC in AA, we failed
      to identify loci for CAC at genome-wide significant levels despite having
      adequate power to detect alleles with moderate to large effects. Although
      suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA
      loci, overall the data suggest that even larger samples and an ethnic specific
      focus will be required for GWAS discoveries for CAC in AA populations.

PMID- 23870197
TI  - Spotted fever group rickettsiae in Dermacentor reticulatus and Haemaphysalis
      punctata ticks in the UK.
AB  - BACKGROUND: Spotted fever group (SFG) rickettsiae have recently been identified
      for the first time in UK ticks. This included the findings of Rickettsia
      helvetica in Ixodes ricinus and Rickettsia raoultii in Dermacentor reticulatus.
      This paper further investigates the occurrence of SFG rickettsiae in additional
      geographically distinct populations of D. reticulatus, and for the first time,
      investigates the occurrence of SFG rickettsiae in UK populations of Haemaphysalis
      punctata ticks. METHODS: Questing D. reticulatus and H. punctata were collected
      at a number of sites in England and Wales. DNA from questing ticks was extracted
      by alkaline lysis and detection of rickettsiae DNA was performed, in addition to
      detection of A. phagocytophilum, N. mikurensis, C. burnetii and B. burgdorferi
      sensu lato. RESULTS: This paper builds on previous findings to include the
      detection of spotted fever Rickettsia which showed the highest homology to
      Rickettsia massiliae in Haemaphysalis punctata, as well as R. helvetica in D.
      reticulatus. The occurrence of SFG rickettsiae in D. reticulatus in the UK
      appears to be confined only to Welsh and Essex populations, with no evidence so
      far from Devon. Similarly, the occurrence of SFG rickettsiae in H. punctata
      appears confined to one of two farms known to be infested with this tick in North
      Kent, with no evidence so far from the Sussex populations. Anaplasma
      phagocytophilum, Neoehrlichia mikurensis, Coxiella burnetii and Borrelia
      burgdorferi sensu lato DNA was not detected in any of the ticks. CONCLUSION:
      These two tick species are highly restricted in their distribution in England and
      Wales, but where they do occur they can be abundant. Following detection of these
      SFG rickettsiae in additional UK tick species, as well as I. ricinus, research
      should now be directed towards clarifying firstly the geographic distribution of
      SFG rickettsiae in UK ticks, and secondly to assess the prevalence rates in
      ticks, wild and domesticated animals and humans to identify the drivers for
      disease transmission and their public health significance.

PMID- 23870198
TI  - Design considerations for studies of the biomechanical environment of the
      femoropopliteal arteries.
AB  - OBJECTIVE: The purpose of this study was to review the available literature
      regarding the biomechanics of the superficial femoral artery (SFA) and popliteal
      artery (PA) in patients with peripheral arterial disease (PAD). Stents are one of
      many available therapies used to treat patients with PAD. Because stents are
      permanent implants, they undergo a variety of deformations as patients go about
      their daily activities such as walking, sitting in a chair, or climbing stairs.
      As a part of the marketing application for United States Food and Drug
      Administration approval, stents need to be evaluated for long-term durability
      under a variety of loading modes. The information available in the literature
      provides direction for such evaluation. METHODS: We performed a literature search
      of the PubMed database looking for "key vessel" and "mechanics" (all fields) or
      "deformation" (all fields) or "flexion" (all fields) or "mechanical environment"
      (all fields) or "tortuosity" (all fields) or "dynamics" (all fields) or "forces"
      (all fields), where the "key vessel" was "Femoral Artery," "Superficial Femoral
      Artery," "Popliteal Artery," and "Femoropopliteal." RESULTS: Using a decision
      tree, we found 12 relevant articles that focused solely on the nonradial cyclic
      deformations associated with musculoskeletal motion. Despite the many limitations
      associated with combining these studies, we learned that under walking
      conditions, the proximal and mid-SFA deforms, on average, by shortening in the
      axial direction 4.0%, by twisting 2.1 degrees /cm, and by bending 72.1 mm; the
      distal SFA and proximal PA deform by shortening in the axial direction 13.9%, by
      twisting 3.5 degrees /cm, and by being pinched such that the aspect ratio of the
      lumen changes 4.6%. The distal PA deforms by shortening in the axial direction
      12.3%, by twisting 3.5 degrees /cm, by bending 22.1 mm, and by being pinched such
      that the aspect ratio of the lumen changes 12.5%. CONCLUSIONS: A review of the
      current literature reveals heterogeneous study designs that confound
      interpretation. Studies included different physiologic settings from young to
      mature participants, participants with and without disease, and cadavers.
      Investigators used a range of imaging modalities and definitions of arterial
      segments, which affected our ability to compile the data as we learned that
      deformations vary according to the specific anatomic location within the SFA/PA.
      As a result of this analysis, we identified design considerations for future
      studies, because although this work has been valuable and significant, there are
      many limitations with the currently available data such that all we know about
      the SFA/PA environment is that we don't know.

PMID- 23870199
TI  - Bufalin, a component in Chansu, inhibits proliferation and invasion of
      hepatocellular carcinoma cells.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a common and aggressive cancer, and
      the treatment options are limited for patients with advanced HCC. Bufalin, the
      major digoxin-like component of the traditional Chinese medicine Chansu, exhibits
      significant anti-tumor activities in many tumor cell lines. In the present study,
      we investigated the effect of bufalin on the inhibition of an AKT-related
      signaling pathway, and examined the relationship between regulatory proteins and
      anti-tumor effects in hepatoma cells. METHODS: Proliferation, wound healing,
      transwell-migration/invasion and adhesion assays were performed in HCCLM3 and
      HepG2 cell lines. The protein levels of pAKT, AKT, pGSK3beta, GSK3beta, pbeta
      catenin, beta-catenin, E-cadherin, MMP-9, and MMP-2 were measured by western blot
      analysis. E-Cadherin and beta-catenin expression levels were also evaluated by
      immunofluorescence. RESULTS: Bufalin inhibited hepatoma cell proliferation,
      migration, invasion and adhesion. In addition, treatment with bufalin
      significantly decreased the levels of pAKT, pGSK3beta, MMP-9, and MMP-2, while
      increasing the levels of GSK3beta and E-cadherin and suppressing the nuclear
      translocation of beta-catenin. CONCLUSIONS: Bufalin is a potential anti-HCC
      therapeutic candidate through its inhibition of the AKT/GSK3beta/beta-catenin/E
      cadherin signaling pathway. Further studies with bufalin are warranted in
      patients with HCC, especially those with the disease at advanced stages.

PMID- 23870200
TI  - Gull-derived trace elements trigger small-scale contamination in a remote
      Mediterranean nature reserve.
AB  - The role of a yellow-legged gull (Larus michahellis) small colony in conveying
      trace elements (As, Cd, Cr, Cu, Ni, Pb, THg, V, Zn) was assessed in a
      Mediterranean nature reserve (Marinello ponds) at various spatial and temporal
      scales. Trace element concentrations in guano were high and seasonally variable.
      In contrast, contamination in the ponds was not influenced by season but showed
      strong spatial variability among ponds, according to the different guano input.
      Biogenic enrichment factor B confirmed the role of gulls in the release of trace
      elements through guano subsidies. In addition, comparing trace element pond
      concentrations to the US NOAA's SQGs, As, Cu and Ni showed contamination levels
      associated with possible negative biological effects. Thus, this study reflects
      the need to take seabirds into account as key factors influencing ecological
      processes and contamination levels even in remote areas, especially around the
      Mediterranean, where these birds are abundant but overlooked. 

PMID- 23870201
TI  - Itch as a patient-reported symptom in ambulatory care visits in the United
      States.
AB  - BACKGROUND: European studies have shown that itch is a widespread symptom, yet
      little is known about its frequency in the United States. OBJECTIVE: We sought to
      describe ambulatory care visits to clinicians in the United States for which itch
      was coded as a patient symptom. METHODS: This study uses retrospective data from
      the National Ambulatory Medical Care Survey from 1999 through 2009. RESULTS: Itch
      was coded as a symptom for an average of 7 million visits per year or
      approximately 1% of all outpatient visits, which was nearly 40% of the number of
      visits for the symptom of low back pain. Patients seen in visits for itch were
      more likely to be black or Asian than other patients (20% vs 14%). They were also
      more likely than other patients to receive a new medication (68% vs 36%) and were
      over twice as likely to receive 2 or more new medications (31% vs 14%).
      LIMITATIONS: Secondary data sets may not optimally capture patient reports and
      some of the procedures or medications may have been ordered for reasons other
      than itch. CONCLUSION: Visits to clinicians for itch represent a sizeable
      proportion of ambulatory care visits in the United States, and research on the
      epidemiology, treatments, and causes of itch should be a priority.

PMID- 23870203
TI  - Psychosocial considerations in pediatric surgery. Preface.

PMID- 23870202
TI  - A systematic review of clinical trials of treatments for the congenital
      ichthyoses, excluding ichthyosis vulgaris.
AB  - BACKGROUND: The ichthyoses comprise a group of inherited disorders of
      keratinization. Because of the need for lifelong treatment, it is important that
      therapies are beneficial, safe, and well tolerated. OBJECTIVES: We sought to
      review the evidence on existing treatments for the congenital ichthyoses,
      excluding ichthyosis vulgaris. METHOD: We undertook a systematic review using the
      methodology of the Cochrane Collaboration. Articles published in MEDLINE, EMBASE,
      and CENTRAL and registered clinical trials were screened. Randomized controlled
      trials involving patients with the inherited ichthyoses, either syndromic or
      nonsyndromic but excluding ichthyosis vulgaris, were considered. RESULTS: Six
      trials met the inclusion criteria. Topical treatments including 5% urea, 20%
      propylene glycol alone or in combination with 5% lactic acid, calcipotriol
      ointment, and liarozole 5% cream showed therapeutic benefit. Oral liarozole, a
      retinoic acid metabolism blocking agent, showed no advantage over oral acitretin.
      LIMITATIONS: Most studies were performed on a small sample of patients and lacked
      methodological and reporting quality. The small number of trials and the nearly
      constant positive results make publication bias likely. The absence of
      standardization of outcome measures precluded the comparison of studies.
      CONCLUSIONS: Topical treatments including emollients, calcipotriol ointment, and
      liarozole cream seem to have therapeutic benefit and a good safety profile,
      although the use of topical calcipotriol is limited by a maximum weekly dose of
      100 g. The advantage of oral liarozole over acitretin is uncertain. Multicenter
      trials comparing oral and topical interventions and evaluation of long-term
      outcomes are needed.

PMID- 23870204
TI  - The pediatric surgeon-patient relationship.
AB  - Though technical aspects of surgical practice are commonly emphasized,
      communication is the most frequent "procedure" employed by surgeons. A good
      patient-physician relationship enhances the quality of surgical care by improving
      outcomes and patient and family satisfaction. There are general principles that
      can enhance communication with all children and families. Employing a
      developmentally sensitive approach that adjusts communication style based on a
      child's cognitive abilities and emotional concerns can further enhance the
      relationship with children of different ages. These communication skills can be
      learned and are improved by practice and self-reflection. 

PMID- 23870205
TI  - Psychosocial implications of pediatric surgical hospitalization.
AB  - The prevalence of childhood surgical illness and injury requiring hospitalization
      suggests the need for implementation of an applied intervention to decrease
      levels of anxiety in these patients. When psychological concerns are not
      addressed in the present moment, potential for long-term negative psychological
      effects occur. To respond to the psychosocial needs of pediatric surgical
      patients it is important to understand foundational stages of development. Age is
      not always directly correlated with developmental stage and attunement to this
      subtle differentiation is essential. Some medical facilities offer services to
      pediatric surgical patients that include education about upcoming procedures as
      well as medical play which offers the opportunity to express emotions correlated
      with the hospitalization experience. This approach is directive in nature and
      controls the process of making sense of the medical environment. An alternative
      is Child Centered Play Therapy (CCPT) which creates an outlet for any emotions
      the children choose to express. CCPT offers comprehensive mental health care
      through a developmentally-appropriate, undirected intervention carried out by a
      mental health therapist and has been shown to reduce perceived and actual
      psychological trauma, anxiety, and behavioral issues in children preparing for
      surgery. 

PMID- 23870206
TI  - Promoting coping in children facing pediatric surgery.
AB  - Surgery is challenging for children and their families, calling upon them to cope
      with an invasive procedure, deal with the uncertainty of the surgical outcome,
      and manage the stress of hospitalization. Contributors to children's distress
      when facing pediatric surgery include their coping style, interactions with their
      parents, developmental level, and temperament. A pragmatic approach is outlined
      that can help surgeons promote successful coping in their patients while at the
      same time fostering successful working relationships with parents. 

PMID- 23870207
TI  - Enhancing working relationships between parents and surgeons.
AB  - The working relationship between parents and surgeons is fundamental in providing
      excellent health care to children and adolescents. The breakdown of this working
      relationship has a significant potential for detrimental effects on individual
      well-being and adverse systemic outcomes. Collaborative, deferential, and
      problematic partnership types of family participation in medical decision-making
      are important models to understand in enhancing and maintaining successful
      working relationships. A pragmatic approach involving prevention, recognition,
      and resolution steps is outlined that can help surgeons to avoid as well as to
      respond effectively to difficult and stressful interactions with parents. 

PMID- 23870208
TI  - Psychoneuroimmunology and the pediatric surgeon.
AB  - The mind-body connection is receiving increasing scrutiny in a large number of
      clinical settings, although research has lagged in the pediatric specialties.
      Psychoneuroimmunology (PNI) is a novel interdisciplinary scientific field that
      examines the relationship of the mind to the patient's neurologic, endocrine, and
      immune systems by examining critical parameters such as the effects of mental
      stress on wound healing and infection rates. Techniques that modify a patient's
      emotional and mental responses to illness and surgery have positive effects on
      their physiology resulting in improved recoveries and higher patient satisfaction
      rates. In the appropriate clinical settings, an awareness of PNI can enhance
      outcomes for pediatric surgical patients. 

PMID- 23870209
TI  - The ethics consultation and the pediatric surgeon.
AB  - The cultural, ethnic, religious, socioeconomic, and educational diversity of the
      patient population and the expanded surgical options provided by innovation and
      technology can pose significant ethical challenges. The questions confronting
      pediatric surgeons and their patients' families have greater complexity, and both
      the pediatric surgeon and the family perceive increasing vulnerability and
      uncertainty. The analysis and management of ethical issues in pediatric surgery
      cannot simply be extrapolated from the approach applied to adult cases. By
      reviewing the history of the events that contributed to the creation and
      utilization of hospital ethics committees and examining the role of the ethics
      consultant in the context of pediatric surgical care, practitioners and trainees
      will be better able to address these multifaceted situations. 

PMID- 23870210
TI  - The pediatric surgeon and palliative care.
AB  - Palliative care is now a core component of pediatric care for children and
      families who are confronting serious illness with a low likelihood of survival.
      Pediatric surgeons, in partnership with pediatric palliative care teams, can play
      a pivotal role in assuring that these patients receive the highest possible
      quality of care. This article outlines a variety of definitions and conceptual
      frameworks, describes decision-making strategies and communication techniques,
      addresses issues of interdisciplinary collaboration and personal self-awareness,
      and illustrates these points through a series of case vignettes, all of which can
      help the pediatric surgeon perform the core tasks of pediatric palliative care. 

PMID- 23870211
TI  - Teaching the psychosocial aspects of pediatric surgery.
AB  - The optimal care of children with surgical diseases requires acquiring skills in
      the psychosocial assessment and therapy of children. Developing and implementing
      a curriculum to teach these concepts to pediatric surgery trainees should result
      in decreased perioperative stress for the child and improved patient outcomes and
      family satisfaction. 

PMID- 23870212
TI  - The significance of experiences of war and migration in older age: long-term
      consequences in child survivors from the Dutch East Indies.
AB  - BACKGROUND: This study examines late consequences of war and migration in both
      non-clinical and clinical samples of child survivors of World War II. This is one
      of the very few studies on the mental health of children who were subjected to
      internment in camps, hiding, and violence under Japanese occupation in the Far
      East. It provides a unique case to learn about the significance of experiences of
      war and migration in later life. METHODS: Long-term sequelae of the Japanese
      persecution in the Dutch East Indies (DEI) in child survivors were studied by
      analyzing sets of standardized questionnaires of 939 persons. Instruments dealt
      with post-traumatic responses, general health, and dissociation. Participants
      were recruited through community services and registers of clinical services.
      Discriminant analyses were conducted to evaluate the significance of early
      experiences in determining group belonging. RESULTS: Compared with age-matched
      controls that lived through the German occupation in the Netherlands during World
      War II, the child survivors from the DEI reported both more trauma-related
      experiences and mental health disturbances in later life. In particular, the
      number of violent events during the war, among which especially internment in a
      camp, contributed to the variation among groups, in support of the significance
      of these disruptive experiences at older age. CONCLUSION: The results underline
      the long-term significance of World War II-related traumatic experiences in the
      population of elderly child survivors who spent their childhood in the former
      DEI.

PMID- 23870213
TI  - 3T diffusion tensor imaging and electroneurography of peripheral nerve: a
      morphofunctional analysis in carpal tunnel syndrome.
AB  - OBJECTIVE: The aim of the study was to assess the diagnostic potential of
      diffusion tensor imaging (DTI) for pathologies of the peripheral nervous system
      (PNS) through clinical, electrophysiological and morphological evaluation of the
      median nerve. METHODS: The present work was a multilevel prospective study
      involving 30 subjects, 15 of whom had carpal tunnel syndrome (CTS) and 15 healthy
      controls. All subjects underwent clinical evaluation through administration of
      the Boston Carpal Tunnel Questionnaire (BCTQ), electroneurography (ENG), 3-Tesla
      magnetic resonance imaging with DTI, and calculation of fractional anisotropy
      (FA) and the apparent diffusion coefficient (ADC) at the flexor retinaculum.
      Tractography was also performed for three-dimensional reconstruction of the route
      of the median nerve through the carpal tunnel. The degree of functional
      impairment was compared with the anatomical damage to the median nerve according
      to ENG and DTI. RESULTS: FA and ADC were significantly correlated with ENG
      parameters of CTS and BCTQ data. Mean FA and ADC values in the CTS patients were
      0.359+/-0.06 and 1.866+/-0.050*10(-3)mm(2)/s, respectively, vs 0.59+/-0.014 and
      1.395+/-0.035*10(-3)mm(2)/s, respectively, in the controls. FA was decreased and
      ADC increased in patients with CTS compared with healthy controls (P<0.05).
      CONCLUSION: DTI parameters were clearly confirmed by both clinical and ENG data
      and, therefore, may be used for the diagnosis of CTS.

PMID- 23870214
TI  - Development of microsatellite markers by transcriptome sequencing in two species
      of Amorphophallus (Araceae).
AB  - BACKGROUND: Amorphophallus is a genus of perennial plants widely distributed in
      the tropics or subtropics of West Africa and South Asia. Its corms contain a high
      level of water-soluble glucomannan; therefore, it has long been used as a
      medicinal herb and food source. Genetic studies of Amorphophallus have been
      hindered by a lack of genetic markers. A large number of molecular markers are
      required for genetic diversity study and improving disease resistance in
      Amorphophallus. Here, we report large scale of transcriptome sequencing of two
      species: Amorphophallus konjac and Amorphophallus bulbifer using deep sequencing
      technology, and microsatellite (SSR) markers were identified based on these
      transcriptome sequences. RESULTS: cDNAs of A. konjac and A. bulbifer were
      sequenced using Illumina HiSeqTM 2000 sequencing technology. A total of 135,822
      non-redundant unigenes were assembled from about 9.66 gigabases, and 19,596 SSRs
      were identified in 16,027 non-redundant unigenes. Di-nucleotide SSRs were the
      most abundant motif (61.6%), followed by tri- (30.3%), tetra- (5.6%), penta-
      (1.5%), and hexa-nucleotides (1%) repeats. The top di- and tri-nucleotide repeat
      motifs included AG/CT (45.2%) and AGG/CCT (7.1%), respectively. A total of 10,754
      primer pairs were designed for marker development. Of these, 320 primers were
      synthesized and used for validation of amplification and assessment of
      polymorphisms in 25 individual plants. The total of 275 primer pairs yielded PCR
      amplification products, of which 205 were polymorphic. The number of alleles
      ranged from 2 to 14 and the polymorphism information content valued ranged from
      0.10 to 0.90. Genetic diversity analysis was done using 177 highly polymorphic
      SSR markers. A phenogram based on Jaccard's similarity coefficients was
      constructed, which showed a distinct cluster of 25 Amorphophallus individuals.
      CONCLUSION: A total of 10,754 SSR markers have been identified in Amorphophallus
      using transcriptome sequencing. One hundred and seventy-seven polymorphic markers
      were successfully validated in 25 individuals. The large number of genetic
      markers developed in the present study should contribute greatly to research into
      genetic diversity and germplasm characterization in Amorphophallus.

PMID- 23870215
TI  - Quantification of risk for early unplanned readmission after rectal resection: a
      single-center study.
AB  - BACKGROUND: Several factors predictive of readmission after colorectal surgery
      have been identified. Although often grouped together in readmission studies,
      colon and rectal resections differ in many ways. The aim of this study was to
      identify factors associated with readmission after rectal resection. STUDY
      DESIGN: We performed a retrospective, single-center cohort study of 565 patients
      who underwent rectal resections at a tertiary referral center in 2010 and 2011.
      The main outcomes measure was readmission within 30 days. Univariate comparison
      between readmitted and nonreadmitted patients was followed by a stepwise logistic
      regression to identify independent risk factors for readmission. RESULTS: There
      were 105 patients (18.6%) readmitted. Indication (inflammatory bowel disease
      [IBD], p = 0.008), type of operation (pelvic pouch surgery, p = 0.02), use of
      laparoscopy (readmission 27.8% vs 14%, p < 0.001), and length of operation (p <
      0.001) were associated with a higher readmission rate on univariate analysis.
      Neither preoperative chemoradiation (p = 0.89) nor American Society of
      Anesthesiologists class (p = 0.09) was associated with readmission. Logistic
      regression showed use of laparoscopy (odds ratio [OR] 1.94, 95% CI 1.23 to 3.07),
      initial diagnosis of IBD (OR 1.84, 95% CI 1.17 to 2.93), and length of operation
      (OR 1.09, 95% CI 1.03 to 1.16 per 30 minutes) to be independent risk factors.
      Risks of readmission were 6.7%, 13.4%, 27.4%, and 27.4% with 0, 1, 2, or 3
      positive risk factors, respectively. CONCLUSIONS: Readmission after rectal
      resection is associated with the indication for surgery and the operative
      technique used. Optimization of factors related to the underlying pathology and
      careful appraisal of the operative technique may result in decreased readmission
      after proctectomy.

PMID- 23870216
TI  - Discussion.

PMID- 23870217
TI  - Effectiveness of an oxidized cellulose patch hemostatic agent in thyroid surgery:
      a prospective, randomized, controlled study.
AB  - BACKGROUND: This single-blinded, prospective, randomized controlled trial
      compared the efficacy and safety of an oxidized cellulose patch (Surgicel
      [Johnson and Johnson]) with conventional procedures for achieving hemostasis in
      thyroid surgery. STUDY DESIGN: The study included 190 patients scheduled for
      thyroidectomy. Patients were randomized into 1 conventionally treated (ligatures
      and bipolar electrocautery) group (n = 92) and a second group, which additionally
      received Surgicel (n = 98). RESULTS: The groups were demographically and
      clinically matched and had similar wound drainage volumes and mean duration of
      surgery. Postoperative bleeding rate was greater in the Surgicel group, yet the
      difference didn't reach statistical significance (p = 0.054). There were no
      significant group differences in postoperative wound infection, seroma,
      hypocalcemia, or recurrent laryngeal nerve palsy. Time to drain removal and
      length of hospital stay were significantly shorter in the conventional group (p <
      0.001). CONCLUSIONS: Routine use of an oxidized cellulose hemostatic agent has no
      advantage over conventional hemostasis and is potentially harmful in thyroid
      surgery.

PMID- 23870218
TI  - Acute kidney injury network staging in geriatric postoperative acute kidney
      injury patients: shortcomings and improvements.
AB  - BACKGROUND: The incidence of acute kidney injury (AKI) is rising, particularly
      among the elderly. However, the optimal risk stratification scheme for these
      patients is unknown. The Acute Kidney Injury Network (AKIN) classification
      application in geriatric patients has not been previously confirmed. STUDY
      DESIGN: In this multicenter study, elderly patients (>65 years old) who had major
      surgery and were admitted to ICUs between January 1, 2002 and December 31, 2008
      were recruited and grouped according to the AKIN creatinine criteria. The utility
      of the AKIN criteria for the prediction of in-hospital mortality was determined
      using Cox proportional hazard regression modeling. RESULTS: A total of 4,240
      eligible patients were identified and separated into "non-AKI" (n = 3,259), AKIN
      1 (n = 582), AKIN 2 (n = 78), and AKIN 3 groups (n = 321). Cox proportional
      hazard regression analysis revealed that the AKIN 3 group has a significantly
      higher hospital mortality compared with the non-AKI group (hazard ratio [HR]
      3.19, 95% CI 2.16 to 4.71; p < 0.001); the AKIN 1 (p = 0.611) and AKIN 2 (p =
      0.104) groups have no significant differences compared with the non-AKI group.
      After excluding patients who received hemodialysis 1 week postoperatively, the
      AKIN 2 group predicted a significantly higher risk of hospital mortality compared
      with the non-AKI group (HR 2.31; p = 0.008). CONCLUSIONS: This is the first study
      to demonstrate the poor applicability of the AKIN classification in the
      prediction of in-hospital mortality in geriatric postoperative AKI patients.
      Consideration of late dialysis status may enhance the discriminative power of
      AKIN in this specific population.

PMID- 23870219
TI  - Implementation of an interactive virtual-world simulation for structured surgeon
      assessment of clinical scenarios.
AB  - BACKGROUND: A novel simulation technology has emerged through the use of online 3
      dimensional virtual worlds in which it is feasible to create virtual patients.
      This study establishes the face, content and construct validity of online 3
      dimensional virtual patients in Second Life (a 3-dimensional virtual world
      accessible via the Internet). STUDY DESIGN: Sixty-three surgeons of the following
      grades participated in this study: intern (n = 20); junior resident (n = 15);
      senior resident (n = 18), and attending (n = 10). All subjects assessed a series
      of 3 virtual patients (level 1) with different surgical presentations, such as
      lower gastrointestinal bleeding, acute pancreatitis, and small bowel obstruction.
      The junior resident group managed an additional 3 cases (level 2) with the same
      presentation but of increasing complexity. The senior resident and attending
      groups completed a total of 9 cases (level 1 to 3). The primary outcomes measures
      were the face and content validity rated on a 7-point Likert scale and a
      performance score based on a performance rating. RESULTS: The simulation
      demonstrated high face and content validity ratings. Eight of 9 cases, with the
      exception of the level 3 small bowel obstruction, demonstrated significant
      differences in performance among the user groups (p < 0.01). Additional subset
      analysis demonstrated that the attending group performed best for performance
      ratings. CONCLUSIONS: This novel form of simulation demonstrated high face and
      content validity. Performance assessed in managing a series of virtual patients
      varies with different levels of surgical training. This simulation can be used to
      differentiate among these levels and can be implemented as a unique form of
      assessment.

PMID- 23870220
TI  - Outcomes of hepatectomy for hepatolithiasis based on 3-dimensional reconstruction
      technique.
AB  - BACKGROUND: The aim of our study was to evaluate the perioperative and long-term
      outcomes of hepatectomy based on 3-dimensional reconstruction technique for
      hepatolithiasis by comparing it with traditional hepatectomy. STUDY DESIGN: From
      December 2005 to September 2012, 56 consecutive patients underwent hepatectomy
      based on 3-dimensional reconstruction technique for hepatolithiasis in our
      hospital (group A). During the same period, 42 patients with hepatolithiasis who
      met the inclusion criteria for hepatectomy were selected for traditional
      hepatectomy (group B). All operations were performed by the authors. There was no
      significant difference in preoperative data between the 2 groups statistically.
      RESULTS: Compared with patients in group B, those in group A had a significantly
      lower stone residual rate (intermediate rate, 3.6% vs 19.0%; final rate, 0% vs
      9.5%) and stone recurrence rate (3.6% vs 23.8%), a lower intrahepatic duct
      stricture residual rate (1.8% vs 14.3%), and a faster operating time (218.8 +/-
      55.5 minutes vs 254.7 +/- 65.6 minutes). Intraoperative blood transfusion,
      intraoperative blood loss, postoperative hospital stay, and recurrent cholangitis
      rate were similar. No significant dominance was found in group A with respect to
      serum aminotransferase level, serum bilirubin level, serum albumin level, and
      prothrombin time. There was a significant dominance in group A for serum
      hemoglobin level (116.3 +/- 16.0 g/L vs 108.0 +/- 13.9 g/L; p < 0.05). Twenty-two
      complications occurred, 10 in group A and 12 in group B. Neither group had any
      perioperative mortality. CONCLUSIONS: Hepatectomy for hepatolithiasis based on 3
      dimensional reconstruction technique is feasible and safe in selected patients.
      Compared with traditional hepatectomy, it is more effective for diagnosis and
      treatment of hepatolithiasis.

PMID- 23870221
TI  - Shared and nonshared familial susceptibility to surgically treated inguinal
      hernia, femoral hernia, incisional hernia, epigastric hernia, and umbilical
      hernia.
AB  - BACKGROUND: The familial risk of abdominal wall hernia (AWH) is largely unknown.
      In addition, it is unknown whether inguinal hernia (IH), femoral hernia (FH),
      incisional hernia (INH), epigastric hernia (EH), and umbilical hernia (UH) share
      familial susceptibility. The aim of this nationwide study was to determine the
      familial risks of concordant AWH (same disease in proband and exposed relative)
      and discordant AWH (different disease in proband and exposed relative). STUDY
      DESIGN: Data from the Swedish Multigeneration Register on individuals aged 0 to
      78 years were linked to the Swedish hospital discharge register and the Swedish
      outpatient register for the period from 1964 to 2010. Standardized incidence
      ratios (SIRs) and 95% CIs for surgically treated IH (n = 209,814 cases), FH (n =
      4,576), INH (n = 19,494), EH (n = 8,257), and UH (n = 22,761) were calculated for
      siblings of individuals with hernia compared with the siblings of unaffected
      individuals. The procedure was repeated for spouses. RESULTS: All concordant and
      most discordant familial sibling risks were increased. Familial concordant SIRs
      for siblings were IH = 1.97 (95% CI, 1.94-1.99), FH = 3.40 (95% CI, 2.44-4.62),
      INH = 2.24 (95% CI, 2.04-2.46), EH = 5.57 (95% CI, 4.64-6.64), and UH = 3.61 (95%
      CI, 3.33-3.91). Concordant familial risks were higher than discordant risks. For
      example, when the proband sibling had IH, the discordant SIRs were FH = 1.74 (95%
      CI, 1.61-1.88), INH = 1.22 (95% CI, 1.16-1.28), EH = 1.30 (95% CI, 1.20-1.40),
      and UH = 1.35 (95% CI, 1.29-1.41). Concordant SIRs for spouses were lower: IH =
      1.23 (95% CI, 1.20-1.26), FH = 0.97 (95% CI, 0.64-1.36), INH = 1.56 (95% CI, 1.41
      1.71), EH = 1.70 (95% CI, 1.09-2.45), and UH = 1.31 (95% CI, 1.09-1.56).
      CONCLUSIONS: Family history of surgically treated AWH is an important risk factor
      for surgical treatment of AWH. The 5 forms of AWH studied share familial
      susceptibility, but site-specific familial factors might exist. Several spouse
      risks were increased, suggesting the possibility of a nongenetic contribution to
      familial risks.

PMID- 23870222
TI  - Intraoperative cholangiography and repair of bile duct injuries.

PMID- 23870223
TI  - The pelvic compartment syndrome.

PMID- 23870224
TI  - Reply: To PMID 23518251.

PMID- 23870225
TI  - Nonoperative approach for ruptured abdominal aortic aneurysm: still an option in
      the 21st century?

PMID- 23870226
TI  - Reply: To PMID 23521956.

PMID- 23870227
TI  - Poor outcomes after emergency laparotomy: the United Kingdom response.

PMID- 23870229
TI  - Percutaneous and reduced-port Roux-en-Y gastric bypass: technical aspects.

PMID- 23870230
TI  - Laparoscopic enterolithotomy for gallstone ileus.

PMID- 23870231
TI  - Portomesenteric reconstruction using an umbilical vein patch during
      pancreaticoduodenectomy (Whipple procedure).

PMID- 23870232
TI  - Response to letter to the editor "Increased prevalence of non-compaction" by
      Finsterer and Mahjoub.

PMID- 23870233
TI  - Gamma Knife radiosurgery in the management of brainstem metastases.
AB  - BACKGROUND: Metastases to the brainstem portend a poor prognosis and present a
      challenge in clinical management. Surgical resection is rarely a viable option.
      METHODS: Post-treatment MRI scans of patients with brainstem metastases treated
      with radiosurgery were used to determine local control and disease progression.
      Median survival was calculated using Kaplan-Meier analysis. Univariate and
      multivariate analyses were performed using log-rank test and Cox proportional
      hazards model, respectively. RESULTS: Thirty-two consecutive patients with
      brainstem metastasis underwent Gamma Knife radiosurgery. Median age was 50 years.
      Median tumor volume was 0.71 cm3 and median tumor margin dose was 13 Gy.
      Seventeen of 32 patients received WBRT prior to stereotactic radiosurgery. Median
      survival was 5.2 months. There was a statistically significant difference in
      survival based on RTOG recursive partition analysis (RPA) class. Median survival
      of patients categorized as RPA class I was 19.2 months, RPA class II was 8.4
      months, and RPA class III was 1.9 months. The overall local tumor control rate
      was 87.5%. There were no acute complications following stereotactic radiosurgery
      and no evidence of radiation necrosis noted on post-treatment MRI scans.
      CONCLUSION: Stereotactic radiosurgery is an effective treatment for brainstem
      metastases and should be considered especially for patients with good performance
      status.

PMID- 23870234
TI  - Factors influencing the intention of women in rural Ghana to adopt postpartum
      family planning.
AB  - BACKGROUND: Uptake of postpartum family planning (PPFP) remains low in sub
      Saharan Africa and very little is known about how pregnant women arrive at their
      decisions to adopt PPFP. This information is needed to guide the development of
      interventions to promote PPFP. METHODS: We conducted a survey among pregnant
      women attending antenatal clinics in a rural district in Ghana. We used
      univariate and multivariate logistic regression analysis to explore how knowledge
      of various family planning (FP) methods, past experience with their use and the
      acceptability of PPFP to male partners and close relations influenced the
      intention of pregnant women to adopt PPFP. RESULTS: We interviewed 1914 pregnant
      women in four health facilities. About 84% considered PPFP acceptable, and 70%
      intended to adopt a method. The most preferred methods were injectables (31.5%),
      exclusive breastfeeding (16.7%), and oral contraceptive pills (14.8%). Women
      whose first choice of PPFP method were injectables were more likely to be women
      who had had past experience with its use (O.R = 2.07, 95% C.I. 1.50-2.87).
      Acceptability of PPFP by the pregnant woman (O.R. = 3.21, 1.64-6.26), perception
      of partner acceptability (O.R. = 3.20, 1.94-5.48), having had prior experience
      with the use of injectables (O.R. = 3.72, 2.61-5.30) were the strongest
      predictors of the intention to adopt PPFP. Conversely women who knew about the
      diaphragm (O.R. = 0.59, 0.38-0.93) and those who had past experience with IUD use
      (O.R. = 0.13, 0.05-0.38) were less likely to want to adopt PPFP. CONCLUSIONS:
      Acceptability of PPFP to the pregnant woman, male partner approval, and past
      experience with the use of injectables are important factors in the PPFP
      decisions of women in this population. Antenatal and early postnatal care need to
      be adapted to take these factors into consideration.

PMID- 23870235
TI  - Laparoscopic hysterectomy for endometrial cancer: an established benefit no
      longer in question.

PMID- 23870236
TI  - Prophylactic salpingectomy: does it make the cut?

PMID- 23870237
TI  - Microlaparoscopy in urogynecology: LSH and sacrocervicopexy.
AB  - STUDY OBJECTIVE: To determine the feasibility of using only microlaparoscopic
      (3.5 mm) accessory instruments for performing laparoscopic supracervical
      hysterectomy (LSH) and sacrocervicopexy with the aid of a transcervically placed
      cannula for introduction of mesh and needles. DESIGN: Retrospective evaluation of
      the first five cases of microlaparoscopic LSH with sacrocervicopexy (Canadian
      Task Force classification III). SETTING: Community teaching hospital affiliated
      with a major teaching hospital. PATIENTS: Five women with symptomatic
      uterovaginal prolapse of stage II or higher. INTERVENTIONS: LSH with
      transcervical morcellation followed by sacrocervicopexy with all 3.5 mm
      instruments using synthetic mesh with anterior and posterior extensions.
      MEASUREMENTS AND MAIN RESULTS: Four ports were made in all patients: a 5-mm
      infraumbilical port for the laparoscope and three 3.5-mm ports (right and left
      paraumbilical and suprapubic). LSH was performed using a 3-mm bipolar grasping
      device and reusable monopolar scissors. Resection of the uterus was also
      performed using monopolar scissors. Transcervical coring through the vagina was
      performed using a 15-mm serrated cylindrical blade with a central rod placed
      upward through the cervix, and transcervical morcellation was performed using an
      electromechanical morcellator. In all patients, sacrocervicopexy was performed
      successfully using Y-shaped polypropylene mesh, with PTFE sutures on the vagina
      and the sacral promontory. Reperitonealization over the mesh was performed using
      a running barbed absorbable suture. There were no intraoperative or postoperative
      complications in this group of patients. CONCLUSION: LSH and sacrocervicopexy
      using 3.5-mm accessory ports is a feasible procedure with the use of
      transcervical morcellation and a transcervical access cannula.

PMID- 23870238
TI  - Nonresectoscopic endometrial ablation in high-risk surgical patients: a cohort
      study.
AB  - STUDY OBJECTIVE: To evaluate the use of nonresectoscopic endometrial ablation in
      women with high anesthetic and surgical risk compared with low-risk women based
      on the American Society of Anesthesia (ASA) physical status stratification.
      DESIGN: This is a cohort study of women who were classified as high-risk (HR) or
      low-risk (LR) cohorts based on ASA physical status stratification. The ASA
      classification includes 6 grades: ASAP1, a normal healthy person; ASAP2, mild
      systemic disease; ASAP3, severe systemic disease; ASAP4, severe systemic disease
      that is a constant threat to life; ASAP5, a critically ill patient who is not
      expected to survive without the operation; and ASAP6, declared brain-dead patient
      whose organs are being removed for donor purposes. Baseline characteristics
      including comorbidities were obtained. Outcome measures included amenorrhea,
      treatment failure, and operative complications. The time to treatment failure was
      compared using Kaplan-Meier analysis. Risk adjustments were performed using
      regression models. SETTING: Academic medical center in the Upper Midwest.
      PATIENTS: Seven-hundred eleven women underwent nonresectoscopic endometrial
      ablation at our institution between January 1998 and December 2005.
      INTERVENTIONS: Bipolar radiofrequency was used in 448 women and thermal balloon
      ablation in 263 women. MEASUREMENTS AND MAIN RESULTS: The HR cohort had a higher
      proportion of women with cardiac disease (27.1% vs. 6.7%, p < .001) and more
      women with nongynecologic cancer (12.3% vs. 2.9%, Fisher exact test, p < .001).
      Nonetheless, endometrial ablation had comparable efficacy in both the HR and LR
      cohorts with 5-year failure rates of 11.7% and 14.8% (p = .659), respectively.
      Amenorrhea rates were also similar in both cohorts (29.7% vs. 27.2%, p = .645).
      After adjusting for known confounders including age, parity, dysmenorrhea,
      previous tubal ligation, uterine length, and the type of the procedure, the
      calculated hazard ratio for failure in the HR cohort was 0.80 (95% confidence
      interval; 0.31-1.74, p = .607), and the adjusted odds ratio for amenorrhea was
      1.27 (95% confidence interval, 0.71-2.20; p = .411). Complications were rare in
      both groups. The mortality rate in the HR cohort was significantly higher
      compared with the LR cohort (7.9% vs. <1%, p < .001), but this was not related to
      the ablation procedures. CONCLUSION: For women who are high anesthetic and
      surgical risks because of serious underlying comorbidities, nonresectoscopic
      endometrial ablation can provide minimally invasive, safe, and effective therapy
      for menorrhagia.

PMID- 23870239
TI  - Comparison of sublingual misoprostol with lidocaine spray for pain relief in
      office hysteroscopy: a randomized, double-blind, placebo-controlled trial.
AB  - STUDY OBJECTIVE: To compare the effectiveness of sublingual misoprostol with
      lidocaine pump spray for office hysteroscopy. DESIGN: Premenopausal women who had
      an indication for office hysteroscopy were included in this randomized, double
      blind, placebo-controlled study. Eighty-two patients were evaluable for the final
      analysis. SETTING: A tertiary referral center. PATIENTS: Premenopausal women who
      had an indication for office hysteroscopy were included. Eighty-two patients were
      evaluable for the final analysis. INTERVENTIONS: Patients were randomized to
      receive either sublingual misoprostol and placebo of lidocaine or lidocaine pump
      spray applied to the cervix and placebo of misoprostol. MEASUREMENTS AND MAIN
      RESULTS: When compared with the lidocaine group, patients in the misoprostol
      group reported less pain by the immediate visual analog scale scores (2.2 +/-
      0.98 vs. 2.6 +/- 0.99, p = .030), whereas visual analog scale scores at 10
      minutes were similar between groups (2.1 +/- 0.98 vs. 2.36 +/- 1.06, p = .156).
      CONCLUSION: Sublingual misoprostol is more effective than lidocaine spray in pain
      reduction during office hysteroscopy. Misoprostol may cause vaginal spotting,
      which may impair the vision during hysteroscopy especially just after the
      menstrual period. Preventive measures should be taken to make the procedure pain
      free because the physician may underestimate pain perception during the
      procedure.

PMID- 23870240
TI  - Systematic implementation of laparoscopic hysterectomy independent of uterus
      size: clinical effect.
AB  - STUDY OBJECTIVE: To investigate the effect of uterine weight on the mode of
      hysterectomy and on perioperative outcomes and to explore how the increasing
      experience in endoscopic techniques influenced our choice of surgical approach to
      hysterectomy to treat benign conditions. DESIGN: Retrospective analysis (Canadian
      Task Force classification II-2). SETTING: University-based department of
      obstetrics and gynecology. PATIENTS: A series of 1518 consecutive women with
      benign uterine conditions other than pelvic organ prolapse who underwent
      hysterectomy at our department between January 2000 and December 2011.
      INTERVENTIONS: Gradual implementation of the laparoscopic approach over years,
      with the goal of attempting endoscopic hysterectomy whenever possible and
      irrespective of uterine weight. Comparisons were made on the basis of various
      approaches to hysterectomy including vaginal hysterectomy (VH), abdominal
      hysterectomy (AH), and total laparoscopic hysterectomy (TLH) and on uterine
      weight. MEASUREMENTS AND MAIN RESULTS: Hysterectomies performed included 568 VH
      (37.4%), 234 AH (15.4%), and 716 TLH (47.2%). Postoperative complications were
      lower in the TLH group vs the AH group; no significant difference was observed
      between the VH vs TLH groups or the AH vs VH groups. A marked reduction in the
      need for open surgery was noted between 2000 and 2011 (p for trend <.001).
      Restricting the analysis to TLH, an increase in operative time and blood loss was
      observed, parallel to increasing uterine weight. Hospital stay and rate of
      intraoperative and postoperative complications were independent of uterine
      weight. In 45 women with uterus weight >=1000 g, the initial approach was via
      laparoscopy, with a success rate of 95.6% (n = 43). A marked tendency toward
      reduction in the use of open surgery was observed through the years when uterine
      weight was >=1 kg (p for trend <.001). CONCLUSION: Systematic implementation of
      laparoscopic hysterectomy enables a marked reduction in the need for AH. In
      experienced hands, even very large uteri (>=1 kg) can be safely removed via
      laparoscopy.

PMID- 23870241
TI  - Physician opinions regarding elective bilateral salpingectomy with hysterectomy
      and for sterilization.
AB  - STUDY OBJECTIVE: To gather opinions about the benefits and concerns of performing
      bilateral salpingectomy without oophorectomy during hysterectomy for benign
      indications and as a sterilization procedure. DESIGN: Survey study (Canadian Task
      Force classification III). SETTING: Practicing physicians in US institutions that
      have obstetrics and gynecology residency programs listed on the FREIDA website
      were surveyed electronically. INTERVENTION: A validated, standardized
      questionnaire designed to gather opinions about bilateral salpingectomy performed
      during hysterectomy or for sterilization was administered via SurveyMonkey to
      practitioners of obstetrics and gynecology. MEASUREMENTS AND MAIN RESULTS:
      Results were compiled and presented as percentages of total responders. A total
      of 234 surveys were returned. Fifty-four percent of physicians perform bilateral
      salpingectomy during hysterectomy, most commonly to reduce the risks of cancer
      (75%) and repeat operation (49.1%). Of the 45.5% of physicians who do not perform
      bilateral salpingectomy during hysterectomy, most (69.4%) believe there is no
      benefit. Fifty-eight percent of practitioners believe that bilateral
      salpingectomy is the most effective method of sterilization after age 35 years
      but choose this method only in patients in whom one sterilization procedure has
      failed or because of tubal disease. Only 7.2% of surgeons prefer it as an
      interval sterilization procedure. CONCLUSION: Most practitioners believe that
      bilateral salpingectomy is beneficial. Most also believe that bilateral
      salpingectomy is the most effective sterilization procedure; however, only 7.2%
      use this method as an interval procedure. More data are needed to evaluate the
      prophylactic effect of bilateral salpingectomy against postoperative sequelae.

PMID- 23870243
TI  - Laparoscopic repair of post-cesarean uterine scar defect.

PMID- 23870242
TI  - Evaluation of clinical usefulness of a medical monitor equipped with an organic
      electroluminescence panel in comparison with liquid crystal display monitors.
AB  - The medical liquid crystal display (LCD) monitor is a conventionally used imaging
      device for diagnosis and during endoscopic surgery. Recently, a medical organic
      electroluminescence panel, the organic light-emitting diode (OLED) monitor, was
      made available commercially. The advantages of the OLED monitor include good
      color reproducibility, high contrast, and high video responsiveness. In this
      nonclinical study, we compared the clinical usefulness and image quality of the
      OLED monitor and those of the LCD monitor using videos of gynecologic endoscopic
      surgeries. Monitors were set for blind evaluation. Five evaluators with varying
      experience in endoscopic surgery evaluated 21 surgery videos played
      simultaneously on an OLED monitor and two LCD monitors for 2 to 3 minutes twice.
      Evaluators judged 13 clinical usefulness indices and 11 image quality indices
      using a 5-point scale (1, very good; 5, very poor) for each video. The mean
      scores of clinical usefulness indices of the OLED monitor and the LCD monitors 1
      and 2 were 2.2 to 2.7, 2.1 to 3.3, and 3.0 to 3.2, respectively. Of seven indices
      measured, five including motion response, the ability to differentiate organs,
      recognize lesions, and reproduce actual images, and the general impression of
      picture quality were statistically superior with use of the OLED monitor compared
      with the LCD monitor 1, and two including ability to distinguish blood vessels
      and the ureters were statistically superior with use of the LCD monitor 1
      compared with the OLED monitor. The mean scores of image quality indices of the
      OLED monitor and the LCD monitors 1 and 2 were 1.8 to 3.2, 2.6 to 3.6, and 2.8 to
      4.0, respectively. Each index of the OLED monitor was superior to or comparable
      with those of the LCD monitors. We conclude that the OLED monitor is superior to
      the LCD monitors insofar as several video presentation characteristics required
      in gynecologic endoscopic surgery. These findings suggest that the OLED monitor
      is expected to contribute detailed assessment of organs and the operative field. 

PMID- 23870244
TI  - Reply: To PMID 23357466.

PMID- 23870246
TI  - Diagnostic yield of repeat upper gastrointestinal endoscopy for patients with
      functional dyspepsia.
AB  - OBJECTIVE: To study the diagnostic yield of repeat upper gastrointestinal
      endoscopy for patients with functional dyspepsia (FD). METHODS: A retrospective
      review of the database including consecutive patients who underwent
      esophagogastroduodenoscopy at least twice for dyspeptic symptoms at a tertiary
      endoscopy center from 1996 to 2011 was performed. The patients' age, gender,
      symptoms and endoscopic and pathological findings were collected and analyzed.
      RESULTS: A total of 2 350 patients with FD with a median age of 50 years,
      including 1020 men and 1330 women, were enrolled. Abdominal pain or discomfort
      was the main indication for the first endoscopy, and 12.6% of the patients
      presented with alarm features. At the second endoscopy, non-atrophic and atrophic
      gastritis were the most common endoscopic findings and only 12 and 10 patients
      were found to have peptic ulcers or gastric polyps, respectively. No malignancy
      was detected at either the first or the repeat endoscopy. CONCLUSIONS:
      Significant pathologies within one year after a normal esophagogastroduodenoscopy
      are very rare for patients with FD. Therefore, a repeat endoscopy within one year
      after the first endoscopy is not recommended for these patients.

PMID- 23870245
TI  - Weaker control of the electrical properties of cerebellar granule cells by
      tonically active GABAA receptors in the Ts65Dn mouse model of Down's syndrome.
AB  - BACKGROUND: Down's syndrome (DS) is caused by triplication of all or part of
      human chromosome 21 and is characterized by a decrease in the overall size of the
      brain. One of the brain regions most affected is the cerebellum, in which the
      number of granule cells (GCs) is markedly decreased. GCs process sensory
      information entering the cerebellum via mossy fibres and pass it on to Purkinje
      cells and inhibitory interneurons. How GCs transform incoming signals depends on
      their input-output relationship, which is adjusted by tonically active GABA(A)
      receptor channels. RESULTS: We report that in the Ts65Dn mouse model of DS, in
      which cerebellar volume and GC number are decreased as in DS, the tonic GABA(A)
      receptor current in GCs is smaller than in wild-type mice and is less effective
      in moderating input resistance and raising the minimum current required for
      action potential firing. We also find that tonically active GABA(A) receptors
      curb the height and broaden the width of action potentials in wild-type GCs but
      not in Ts65Dn GCs. Single-cell real-time quantitative PCR reveals that these
      electrical differences are accompanied by decreased expression of the gene
      encoding the GABA(A) receptor beta3 subunit but not genes coding for some of the
      other GABA(A) receptor subunits expressed in GCs (alpha1, alpha6, beta2 and
      delta). CONCLUSIONS: Weaker moderation of excitability and action potential
      waveform in GCs of the Ts65Dn mouse by tonically active GABA(A) receptors is
      likely to contribute to atypical transfer of information through the cerebellum.
      Similar changes may occur in DS.

PMID- 23870247
TI  - Long term follow up of congenital thrombotic thrombocytopenic purpura (Upshaw
      Schulman syndrome) on hemodialysis for 19 years: a case report.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is frequently associated
      with renal abnormalities, but there have been few reports about renal
      abnormalities in patients with hereditary TTP. In particular, little is known
      about the long-term prognosis of patients with childhood-onset congenital TTP.
      CASE PRESENTATION: We report a Japanese patient with congenital TTP (Upshaw
      Schulman syndrome) who was followed for 19 years after initiation of hemodialysis
      when he was 22 years old. At the age of 6 years, the first episode of purpura,
      thrombocytopenia, and proteinuria occurred without any precipitating cause. He
      underwent living-related donor kidney transplantation from his mother, but the
      graft failed after 5 months due to recurrence of TTP. Even after resection of the
      transplanted kidney and resumption of regular hemodialysis, TTP became refractory
      to infusion of fresh frozen plasma (FFP). Therefore, splenectomy was performed
      and his disease remained in remission for 10 years. However, TTP recurred at the
      age of 39 years. Plasma activity of ADAMTS13 (a disintegrin and metalloprotease
      with thrombospondin type I domain 13) was less than 3%, while ADAMTS13 inhibitor
      was not detected (<0.5 Bethesda units/mL). The patient died suddenly after
      hemodialysis at the age of 41 years. Subsequent genetic analysis of this patient
      and his parents revealed two different heterozygous mutations of ADAMTS13,
      including a missense mutation in exon 26 (c.T3650C causing p.I1217T) inherited
      from his father and a missense mutation in exon 21 (c.G2723A causing p.C908Y)
      inherited from his mother. The former mutation has not been detected before in
      Japan, while the latter mutation is common in Japan. A retrospective review
      showed that serum C3 levels were consistently low while C4 levels were normal
      during follow-up, and C3 decreased much further during each episode of TTP.
      CONCLUSION: Congenital TTP was diagnosed from the clinical, biochemical, and
      genetic findings. Infusion of FFP controlled each thrombotic episode, but the
      effect was limited and of short duration. Review of the complement profile in
      this patient suggested that a persistently low serum C3 level might be associated
      with refractory TTP and a worse renal prognosis.

PMID- 23870248
TI  - Assessment of plaque evolution in coronary bifurcations located beyond everolimus
      eluting scaffolds: serial intravascular ultrasound virtual histology study.
AB  - PURPOSE: To evaluate the atherosclerotic evolution in coronary bifurcations
      located proximally and distally to a bioresorbable scaffold. METHODS: Thirty
      bifurcations located >5 mm beyond the scaffolded segment, being investigated with
      serial intravascular ultrasound virtual histology (IVUS-VH) examinations, at
      baseline and 2-years, in patients enrolled in the ABSORB cohort B1 study were
      included in this analysis. In each bifurcation, the frames portraying the
      proximal rim, in-bifurcation, and distal rim of the ostium of the side branch
      were analyzed. The geometric parameters and plaque types were evaluated at
      baseline and 2-years follow-up. RESULTS: There were no significant differences in
      the geometrical parameters such as lumen, vessel and plaque areas as well as in
      the composition of the atheroma between baseline and 2-years follow-up.When we
      separately examined the bifurcations located proximally and distally to the
      scaffolded segment, no changes were found at the distal bifurcations, while at
      the proximal bifurcations there was a statistical significant decrease in the
      plaque burden (36.67 +/- 13.33% at baseline vs. 35.06 +/- 13.20% at 2 years
      follow-up, p = 0.04).Ten necrotic core rich plaques were found at baseline, of
      which 2 regressed to either fibrotic plaque or to intimal thickening at 2 years
      follow-up. The other 8 did not change. Disease progression was noted in 3 plaques
      (1 adaptive intimal thickening, 1 fibrotic and 1 fibrocalcific plaque) that
      evolved to necrotic rich plaques. CONCLUSIONS: Plaque regression was noted at the
      bifurcations located proximally to the bioresorbable scaffold but not at these
      located distally. Additional studies are required to confirm this finding and
      examine further the effect of drug elution on atherosclerotic evolution.

PMID- 23870249
TI  - Structural characterization and inhibition of toxic amyloid-beta oligomeric
      intermediates.

PMID- 23870250
TI  - The mechanism of detergent solubilization of lipid bilayers.
AB  - Multiple data are available on the self-assembly of mixtures of bilayer-forming
      amphiphiles, particularly phospholipids and micelle-forming amphiphiles, commonly
      denoted detergents. The structure of such mixed assemblies has been thoroughly
      investigated, described in phase diagrams, and theoretically rationalized in
      terms of the balance between the large spontaneous curvature of the curvophilic
      detergent and the curvophobic phospholipids. In this critical review, we discuss
      the mechanism of this process and try to explain the actual mechanism involved in
      solubilization. Interestingly, membrane solubilization by some detergents is
      relatively slow and the common attribute of these detergents is that their trans
      bilayer movement, commonly denoted flip-flop, is very slow. Only detergents that
      can flip into the inner monolayer cause relatively rapid solubilization of
      detergent-saturated bilayers. This occurs via the following sequence of events:
      1), relatively rapid penetration of detergent monomers into the outer monolayer;
      2), trans-membrane equilibration of detergent monomers between the two
      monolayers; 3), saturation of the bilayer by detergents and consequent
      permeabilization of the membrane; and 4), transition of the whole bilayer to
      thread-like mixed micelles. When the detergent cannot flip to the inner
      monolayer, the outer monolayer becomes unstable due to mass imbalance between the
      monolayers and inclusion of the curvophilic detergent molecules in a flat
      surface. Consequently, the outer monolayer forms mixed micellar structures within
      the outer monolayer. Shedding of these micelles into the aqueous solution results
      in partial solubilization. The consequent leakage of detergent into the liposome
      results in trans-membrane equilibration of detergent and subsequent micellization
      through the rapid bilayer-saturation mechanism.

PMID- 23870251
TI  - The effect of the endothelial cell cortex on atomic force microscopy
      measurements.
AB  - We examined whether the presence of the cell cortex might explain, in part, why
      previous studies using atomic force microscopy (AFM) to measure cell modulus (E)
      gave higher values with sharp tips than for larger spherical tips. We confirmed
      these AFM findings in human umbilical vein endothelial cells (HUVEC) and
      Schlemm's canal (SC) endothelial cells with AFM indentation <= 400 nm, two cell
      types with prominent cortices (312 +/- 65 nm in HUVEC and 371 +/- 91 nm in SC
      cells). With spherical tips, E (kPa) was 0.71 +/- 0.16 in HUVEC and 0.94 +/- 0.06
      in SC cells. Much higher values of E were measured using sharp tips: 3.23 +/-
      0.54 in HUVEC and 6.67 +/- 1.07 in SC cells. Previous explanations for this
      difference such as strain hardening or a substrate effect were shown to be
      inconsistent with our measurements. Finite element modeling studies showed that a
      stiff cell cortex could explain the results. In both cell types, Latrunculin-A
      greatly reduced E for sharp and rounded tips, and also reduced the ratio of the
      values measured with a sharp tip as compared to a rounded tip. Our results
      suggest that the cell cortex increases the apparent endothelial cell modulus
      considerably when measured using a sharp AFM tip.

PMID- 23870252
TI  - Large uptake of titania and iron oxide nanoparticles in the nucleus of lung
      epithelial cells as measured by Raman imaging and multivariate classification.
AB  - It is a challenging task to characterize the biodistribution of nanoparticles in
      cells and tissue on a subcellular level. Conventional methods to study the
      interaction of nanoparticles with living cells rely on labeling techniques that
      either selectively stain the particles or selectively tag them with tracer
      molecules. In this work, Raman imaging, a label-free technique that requires no
      extensive sample preparation, was combined with multivariate classification to
      quantify the spatial distribution of oxide nanoparticles inside living lung
      epithelial cells (A549). Cells were exposed to TiO2 (titania) and/or alpha
      FeO(OH) (goethite) nanoparticles at various incubation times (4 or 48 h). Using
      multivariate classification of hyperspectral Raman data with partial least
      squares discriminant analysis, we show that a surprisingly large fraction of
      spectra, classified as belonging to the cell nucleus, show Raman bands associated
      with nanoparticles. Up to 40% of spectra from the cell nucleus show Raman bands
      associated with nanoparticles. Complementary transmission electron microscopy
      data for thin cell sections qualitatively support the conclusions.

PMID- 23870253
TI  - Unraveling the nanoscale surface properties of chitin synthase mutants of
      Aspergillus fumigatus and their biological implications.
AB  - Understanding the surface properties of the human opportunistic pathogen
      Aspergillus fumigatus conidia is essential given the important role they play
      during the fungal interactions with the human host. Although chitin synthases
      with myosin motor-like domain (CSM) play a major role in cell wall biosynthesis,
      the extent to which deletion of the CSM genes alter the surface structural and
      biophysical-biological properties of conidia is not fully characterized. We used
      three complementary atomic force microscopy techniques-i.e., structural imaging,
      chemical force microscopy with hydrophobic tips, and single-molecule force
      spectroscopy with lectin tips-to gain detailed insights into the nanoscale
      surface properties (ultrastructure, hydrophobicity) and polysaccharide
      composition of the wild-type and the chitin synthase mutant (DeltacsmA,
      DeltacsmB, and DeltacsmA/csmB) conidia of A. fumigatus. Wild-type conidia were
      covered with a highly hydrophobic layer of rodlet nanostructures. By contrast,
      the surface of the DeltacsmA mutant was almost completely devoid of rodlets,
      leading to loss of hydrophobicity and exposure of mannan and chitin
      polysaccharides. The DeltacsmB and DeltacsmA/csmB mutants showed a different
      behavior, i.e., the surfaces featured poorly organized rodlet layers, yet with a
      low hydrophobicity and substantial amounts of exposed mannan and chitin at the
      surface. As the rodlet layer is important for masking recognition of immunogenic
      fungal cell wall components by innate immune cells, disappearance of rodlet
      layers in all three chitin synthase mutant conidia was associated with an
      activation of human dendritic cells. These nanoscale analyses emphasize the
      important and distinct roles that the CSMA and CSMB genes play in modulating the
      surface properties and immune interactions of A. fumigatus and demonstrate the
      power of atomic force microscopy in fungal genetic studies for assessing the
      phenotypic characteristics of mutants altered in cell surface organization.

PMID- 23870254
TI  - Analysis of AQP4 trafficking vesicle dynamics using a high-content approach.
AB  - Aquaporin-4 (AQP4) is found on the basolateral plasma membrane of a variety of
      epithelial cells, and it is widely accepted that microtubules play an important
      role in protein trafficking to the plasma membrane. In the particular case of
      polarized trafficking, however, most evidence on the involvement of microtubules
      has been obtained via biochemistry experiments and single-shot microscopy. These
      approaches have provided essential information, even though they neglect the
      dynamical details of microtubule transport. In this work, we present a high
      content framework in which time-lapse imaging, and single-particle-tracking
      algorithms were used to study a large number (~10(4)) of GFP-AQP4-carrying
      vesicles on a large number of cells (~170). By analyzing several descriptors in
      this large sample of trajectories, we were able to obtain highly statistically
      significant results. Our results support the hypothesis that AQP4 is transported
      along microtubules, but to our surprise, this transport is not directed straight
      to the basolateral plasma membrane. On the contrary, these vesicles move
      stochastically along microtubules, changing direction repeatedly. We propose that
      the role of microtubules in the basolateral trafficking of AQP4 is to increase
      the efficiency, rather than determine the specificity of the target.

PMID- 23870255
TI  - Use of rapid-scan EPR to improve detection sensitivity for spin-trapped radicals.
AB  - The short lifetime of superoxide and the low rates of formation expected in vivo
      make detection by standard continuous wave (CW) electron paramagnetic resonance
      (EPR) challenging. The new rapid-scan EPR method offers improved sensitivity for
      these types of samples. In rapid-scan EPR, the magnetic field is scanned through
      resonance in a time that is short relative to electron spin relaxation times, and
      data are processed to obtain the absorption spectrum. To validate the application
      of rapid-scan EPR to spin trapping, superoxide was generated by the reaction of
      xanthine oxidase and hypoxanthine with rates of 0.1-6.0 MUM/min and trapped with
      5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide (BMPO). Spin trapping with
      BMPO to form the BMPO-OOH adduct converts the very short-lived superoxide radical
      into a more stable spin adduct. There is good agreement between the hyperfine
      splitting parameters obtained for BMPO-OOH by CW and rapid-scan EPR. For the same
      signal acquisition time, the signal/noise ratio is >40 times higher for rapid
      scan than for CW EPR. Rapid-scan EPR can detect superoxide produced by
      Enterococcus faecalis at rates that are too low for detection by CW EPR.

PMID- 23870256
TI  - Analysis of the kinetics and bistability of ubiquinol:cytochrome c
      oxidoreductase.
AB  - Ubiquinol:cytochrome c oxidoreductase, bc1 complex, is the enzyme in the
      respiratory chain of mitochondria responsible for the transfer reducing potential
      from ubiquinol to cytochrome c coupled to the movement of charge against the
      electrostatic potential across the mitochondrial inner membrane. The complex is
      also implicated in the generation of reactive oxygen species under certain
      conditions and is thus a contributor to cellular oxidative stress. Here, a
      biophysically detailed, thermodynamically consistent model of the bc1 complex for
      mammalian mitochondria is developed. The model incorporates the major redox
      centers near the Qo- and Qi-site of the enzyme, includes the pH-dependent redox
      reactions, accounts for the effect of the proton-motive force of the reaction
      rate, and simulates superoxide production at the Qo-site. The model consists of
      six distinct states characterized by the mobile electron distribution in the
      enzyme. Within each state, substates that correspond to various electron
      localizations exist in a rapid equilibrium distribution. The steady-state
      equation for the six-state system is parameterized using five independent data
      sets and validated in comparison to additional experimental data. Model analysis
      suggests that the pH-dependence on turnover is primarily due to the pKa values of
      cytochrome bH and Rieske iron sulfur protein. A previously proposed kinetic
      scheme at the Qi-site where ubiquinone binds to only the reduced enzyme and
      ubiquinol binds to only the oxidized enzyme is shown to be thermodynamically
      infeasible. Moreover, the model is able to reproduce the bistability phenomenon
      where at a given overall flux through the enzyme, different rates of superoxide
      production are attained when the enzyme is differentially reduced. 

PMID- 23870257
TI  - Rates and stoichiometries of metal ion probes of cysteine residues within ion
      channels.
AB  - Metal ion probes are used to assess the accessibility of cysteine side chains in
      polypeptides lining the conductive pathways of ion channels and thereby determine
      the conformations of channel states. Despite the widespread use of this approach,
      the chemistry of metal ion-thiol interactions has not been fully elucidated.
      Here, we investigate the modification of cysteine residues within a protein pore
      by the commonly used Ag(+) and Cd(2+) probes at the single-molecule level, and
      provide rates and stoichiometries that will be useful for the design and
      interpretation of accessibility experiments. 

PMID- 23870258
TI  - Calcium transport and local pool regulate polycystin-2 (TRPP2) function in human
      syncytiotrophoblast.
AB  - Polycystin-2 (PC2, TRPP2) is a Ca(2+)-permeable, nonselective cation channel
      implicated in Ca(2+) transport and epithelial cell signaling. Although PC2 may
      contribute to Ca(2+) transport in human term placenta, the regulatory mechanisms
      associated with Ca(2+) handling in this tissue are largely unknown. In this work
      we assessed the regulation by Ca(2+) of PC2 channel function from a preparation
      of apical membranes of human syncytiotrophoblast (PC2hst) reconstituted in a
      lipid bilayer system. Addition of either EGTA or BAPTA to the cis hemi-chamber,
      representing the cytoplasmic domain of the channel, and lowering Ca(2+) to ~0.6
      0.8 nM, inhibited spontaneous PC2hst channel activity, with a time response
      dependent on the chelator tested. EGTA reduced PC2hst channel currents by 86%,
      with a t1/2 = 3.6 min, whereas BAPTA rapidly and completely (100%) eliminated
      channel activity with a t1/2 = 0.8 min. Subsequent titration with Ca(2+) reversed
      the inhibition, which followed a Hill-type function with apparent dissociation
      constants of 1-5 nM, and 4 Ca(2+) binding sites. The degree of inhibition by the
      cis Ca(2+) chelator largely depended on increasing trans Ca(2+). This was
      consistent with measurable Ca(2+) transport through the channel, feeding the
      regulatory sites in the cytoplasmic domain. Interestingly, the reconstituted in
      vitro translated PC2 (PC2iv) was completely insensitive to Ca(2+) regulation,
      suggesting that the regulatory sites are not intrinsic to the channel protein.
      Our findings demonstrate the presence of a Ca(2+) microdomain largely accessible
      through the channel that controls PC2 function in human syncytiotrophoblast of
      term placenta.

PMID- 23870259
TI  - TcdA1 of Photorhabdus luminescens: electrophysiological analysis of pore
      formation and effector binding.
AB  - Tc toxins are widely distributed among different gram-negative and gram-positive
      bacteria, where they act as pathogenicity factors. The toxins are composed of
      different components that form oligomers for biological activity. Lipid bilayer
      experiments were performed with the TcdA1 component of the Tc toxin from
      Photorhabdus luminescens, which preferentially kills insects by actin
      polymerization. TcdA1 was able to increase the specific conductance of artificial
      lipid bilayer membranes by the formation of ion-permeable channels. The channels
      had on average a single-channel conductance of 125 pS in 150 mM KCl and were
      found to be cation selective. The single-channel conductance of the TcdA1
      channels was only moderately dependent on the bulk aqueous KCl concentration,
      which indicated point-charge effects on the channel properties. Experiments to
      study the voltage dependence of the TcdA1 channel demonstrated that it is
      reconstituted in a fully oriented way when it is added to only one side of the
      lipid bilayer membrane. A combination of biologically active components (TccC3)
      and a possible chaperone (TcdB2) blocked the TcdA1-mediated conductance
      efficiently in a dose-dependent manner when they were added to the cis side of
      the membrane. The half-saturation constant for binding of TcdB2-TccC3 to TcdA1 is
      in the low nanomolar range.

PMID- 23870260
TI  - The EF loop in green proteorhodopsin affects conformation and photocycle
      dynamics.
AB  - The proteorhodopsin family consists of retinal proteins of marine bacterial
      origin with optical properties adjusted to their local environments. For green
      proteorhodopsin, a highly specific mutation in the EF loop, A178R, has been found
      to cause a surprisingly large redshift of 20 nm despite its distance from the
      chromophore. Here, we analyze structural and functional consequences of this EF
      loop mutation by time-resolved optical spectroscopy and solid-state NMR. We found
      that the primary photoreaction and the formation of the K-like photo intermediate
      is almost pH-independent and slower compared to the wild-type, whereas the decay
      of the K-intermediate is accelerated, suggesting structural changes within the
      counterion complex upon mutation. The photocycle is significantly elongated
      mainly due to an enlarged lifetime of late photo intermediates. Multidimensional
      MAS-NMR reveals mutation-induced chemical shift changes propagating from the EF
      loop to the chromophore binding pocket, whereas dynamic nuclear polarization
      enhanced (13)C-double quantum MAS-NMR has been used to probe directly the
      retinylidene conformation. Our data show a modified interaction network between
      chromophore, Schiff base, and counterion complex explaining the altered optical
      and kinetic properties. In particular, the mutation-induced distorted structure
      in the EF loop weakens interactions, which help reorienting helix F during the
      reprotonation step explaining the slower photocycle. These data lead to the
      conclusion that the EF loop plays an important role in proton uptake from the
      cytoplasm but our data also reveal a clear interaction pathway between the EF
      loop and retinal binding pocket, which might be an evolutionary conserved
      communication pathway in retinal proteins.

PMID- 23870261
TI  - Growth of large and highly ordered 2D crystals of a K+ channel, structural role
      of lipidic environment.
AB  - 2D crystallography has proven to be an excellent technique to determine the 3D
      structure of membrane proteins. Compared to 3D crystallography, it has the
      advantage of visualizing the protein in an environment closer to the native one.
      However, producing good 2D crystals is still a challenge and little statistical
      knowledge can be gained from literature. Here, we present a thorough screening of
      2D crystallization conditions for a prokaryotic inwardly rectifying potassium
      channel (>130 different conditions). Key parameters leading to very large and
      well-organized 2D crystals are discussed. In addition, the problem of formation
      of multilayers during the growth of 2D crystals is also addressed. An
      intermediate resolution projection map of KirBac3.1 at 6 A is presented, which
      sheds (to our knowledge) new light on the structure of this channel in a lipid
      environment.

PMID- 23870262
TI  - Individual vesicle fusion events mediated by lipid-anchored DNA.
AB  - Membrane fusion consists of a complex rearrangement of lipids and proteins that
      results in the merger of two lipid bilayers. We have developed a model system
      that employs synthetic DNA-lipid conjugates as a surrogate for the membrane
      proteins involved in the biological fusion reaction. We previously showed that
      complementary DNA-lipids, inserted into small unilamellar vesicles, can mediate
      membrane fusion in bulk. Here, we use a model membrane architecture developed in
      our lab to directly observe single-vesicle fusion events using fluorescence
      microscopy. In this system, a planar tethered membrane patch serves as the target
      membrane for incoming vesicles. This allows us to quantify the kinetics and
      characteristics of individual fusion events from the perspective of the lipids or
      the DNA-lipids involved in the process. We find that the fusion pathways are
      heterogeneous, with an arrested hemi-fusion state predominating, and we
      quantitate the outcome and rate of fusion events to construct a mechanistic model
      of DNA-mediated vesicle fusion. The waiting times between docking and fusion are
      distributed exponentially, suggesting that fusion occurs in a single step. Our
      analysis indicates that when two lipid bilayers are brought into close proximity,
      fusion occurs spontaneously, with little or no dependence on the number of DNA
      hybrids formed. 

PMID- 23870263
TI  - Single-virus fusion experiments reveal proton influx into vaccinia virions and
      hemifusion lag times.
AB  - Recent studies have revealed new insights into the endocytosis of vaccinia virus
      (VACV). However, the mechanism of fusion between viral and cellular membranes
      remains unknown. We developed a microfluidic device with a cell-trap array for
      immobilization of individual cells, with which we analyzed the acid-dependent
      fusion of single virions. VACV particles incorporating enhanced green fluorescent
      protein (EGFP) and labeled with self-quenching concentrations of R18 membrane dye
      were used in combination with total internal reflection fluorescence microscopy
      to measure the kinetics of R18 dequenching and thus single hemifusion events
      initiated by a fast low-pH trigger. These studies revealed unexpectedly long lag
      phases between pH change and hemifusion. In addition, we found that EGFP
      fluorescence in the virus was quenched upon acidification, indicating that
      protons could access the virus core, possibly through a proton channel. In a
      fraction of virus particles, EGFP fluorescence was recovered, presumably after
      fusion-pore formation and exposure of the core to the physiological pH of the
      host-cell cytosol. Given that virus-encoded cation channels play a crucial role
      in the life cycle of many viruses and can serve as antiviral drug targets,
      further investigations into a potential VACV viroporin are justified. Our
      findings indicate that the microfluidic device described may be highly beneficial
      to similar studies requiring fast kinetic measurements.

PMID- 23870264
TI  - Statistical analysis of peptide-induced graded and all-or-none fluxes in giant
      vesicles.
AB  - Antimicrobial, cytolytic, and cell-penetrating peptides induce pores or
      perturbations in phospholipid membranes that result in fluxes of dyes into or out
      of lipid vesicles. Here we examine the fluxes induced by four of these membrane
      active peptides in giant unilamellar vesicles. The type of flux is determined
      from the modality of the distributions of vesicles as a function of their dye
      content using the statistical Hartigan dip test. Graded and all-or-none fluxes
      correspond to unimodal and bimodal distributions, respectively. To understand how
      these distributions arise, we perform Monte Carlo simulations of peptide-induced
      dye flux into vesicles using a very simple model. The modality of the
      distributions depends on the rate constants of pore opening and closing, and dye
      flux. If the rate constants of pore opening and closing are both much smaller
      than that of dye flux through the pore, all-or-none influx occurs. However, if
      one of them, especially the rate constant for pore opening, increases
      significantly relative to the flux rate constant, the process becomes graded. In
      the experiments, we find that the flux type is the same in giant and large
      vesicles, for all peptides except one. But this one exception indicates that the
      flux type cannot be used to unambiguously predict the mechanism of membrane
      permeabilization by the peptides. 

PMID- 23870265
TI  - Coarsening dynamics of domains in lipid membranes.
AB  - We investigate isothermal diffusion and growth of micron-scale liquid domains
      within membranes of free-floating giant unilamellar vesicles with diameters
      between 80 and 250 MUm. Domains appear after a rapid temperature quench, when the
      membrane is cooled through a miscibility phase transition such that coexisting
      liquid phases form. In membranes quenched far from a miscibility critical point,
      circular domains nucleate and then progress within seconds to late stage
      coarsening in which domains grow via two mechanisms 1), collision and coalescence
      of liquid domains, and 2), Ostwald ripening. Both mechanisms are expected to
      yield the same growth exponent, alpha = 1/3, where domain radius grows as
      time(alpha). We measure alpha = 0.28 +/- 0.05, in excellent agreement. In
      membranes close to a miscibility critical point, the two liquid phases in the
      membrane are bicontinuous. A quench near the critical composition results in
      rapid changes in morphology of elongated domains. In this case, we measure alpha
      = 0.50 +/- 0.16, consistent with theory and simulation.

PMID- 23870266
TI  - Quantifying the diffusion of membrane proteins and peptides in black lipid
      membranes with 2-focus fluorescence correlation spectroscopy.
AB  - Protein diffusion in lipid membranes is a key aspect of many cellular signaling
      processes. To quantitatively describe protein diffusion in membranes, several
      competing theoretical models have been proposed. Among these, the Saffman
      Delbruck model is the most famous. This model predicts a logarithmic dependence
      of a protein's diffusion coefficient on its inverse hydrodynamic radius (D ? ln
      1/R) for small radius values. For large radius values, it converges toward a D ?
      1/R scaling. Recently, however, experimental data indicate a Stokes-Einstein-like
      behavior (D ? 1/R) of membrane protein diffusion at small protein radii. In this
      study, we investigate protein diffusion in black lipid membranes using dual-focus
      fluorescence correlation spectroscopy. This technique yields highly accurate
      diffusion coefficients for lipid and protein diffusion in membranes. We find that
      despite its simplicity, the Saffman-Delbruck model is able to describe protein
      diffusion extremely well and a Stokes-Einstein-like behavior can be ruled out.

PMID- 23870267
TI  - Exchangeable colloidal AFM probes for the quantification of irreversible and long
      term interactions.
AB  - An original method is presented to study single-colloid interaction with a
      substrate in liquid environment. Colloids, either in solution or adsorbed on a
      surface, are fixed by suction against the aperture of a microchanneled atomic
      force microscopy cantilever. Their adhesion to the substrate is measured,
      followed by their release via a short overpressure surge. Such colloid exchange
      procedure allows for 1), the quick variation of differently functionalized
      colloids within the same experiment; 2), the investigation of long-term
      interactions by leaving the colloids on a surface for a defined time before
      detaching them; and 3), the inspection of irreversible interactions. After
      validation of the method by reproducing literature results obtained with
      traditional colloidal atomic force microscopy, the serial use of colloids with
      different surface functionalization was shown on a micropatterned surface.
      Finally, concanavalin A-coated colloids were allowed to adsorb on human embryonic
      kidney cells and then detached one by one. The adhesion between cells and
      colloids was up to 60 nN, whereas individual cells adhered with 20 nN to the
      glass substrate. A cellular elastic modulus of 0.8 kPa was determined using the
      attached colloid as indenter.

PMID- 23870268
TI  - Abeta association inhibition by transferrin.
AB  - The iron-transport glycoprotein transferrin has recently been shown to serve as a
      potent inhibitor of Abeta self-association. Although this novel, to our
      knowledge, inhibitory function of transferrin is of potential therapeutic
      interest for the treatment of Alzheimer's disease, the underlying mechanism is
      still not fully understood. Although it has been shown that the Fe(III)
      sequestration by transferrin reduces oxidative damage and Abeta aggregation, it
      is not clear whether transferrin is also able to inhibit Abeta self-association
      through direct binding of Abeta. Here, using saturation transfer and off
      resonance relaxation NMR spectroscopy, we show that transferrin inhibits Abeta
      aggregation also by preferentially binding Abeta oligomers and outcompeting Abeta
      monomers that would otherwise cause the growth of the Abeta oligomers into larger
      assemblies. This inhibitory mechanism is different from the iron-sequestration
      model, but it is qualitatively similar to a mechanism previously proposed for the
      inhibition of Abeta self-association by another plasma and cerebrospinal fluid
      protein, i.e., human serum albumin. These results suggest that Abeta monomer
      competition through direct Abeta oligomer binding might be a general strategy
      adopted by proteins in plasma and cerebrospinal fluid to prevent Abeta
      aggregation. 

PMID- 23870269
TI  - NMR determines transient structure and dynamics in the disordered C-terminal
      domain of WASp interacting protein.
AB  - WASp-interacting protein (WIP) is a 503-residue proline-rich polypeptide
      expressed in human T cells. The WIP C-terminal domain binds to Wiskott-Aldrich
      syndrome protein (WASp) and regulates its activation and degradation, and the WIP
      WASp interaction has been shown to be critical for actin polymerization and
      implicated in the onset of WAS and X-linked thrombocytopenia. WIP is predicted to
      be an intrinsically disordered protein, a class of polypeptides that are of great
      interest because they violate the traditional structure-function paradigm. In
      this first (to our knowledge) study of WIP in its unbound state, we used NMR to
      investigate the biophysical behavior of WIP(C), a C-terminal domain fragment of
      WIP that includes residues 407-503 and contains the WASp-binding site. In light
      of the poor spectral dispersion exhibited by WIP(C) and the high occurrence (25%)
      of proline residues, we employed 5D-NMR(13)C-detected NMR experiments with
      nonuniform sampling to accomplish full resonance assignment. Secondary chemical
      shift analysis, (15)N relaxation rates, and protection from solvent exchange all
      concurred in detecting transient structure located in motifs that span the WASp
      binding site. Residues 446-456 exhibited a propensity for helical conformation,
      and an extended conformation followed by a short, capped helix was observed for
      residues 468-478. The (13)C-detected approach allows chemical-shift assignment in
      the WIP(C) polyproline stretches and thus sheds light on their conformation and
      dynamics. The effects of temperature on chemical shifts referenced to a denatured
      sample of the polypeptide demonstrate that heating reduces the structural
      character of WIP(C). Thus, we conclude that the disordered WIP(C) fragment is
      comprised of regions with latent structure connected by flexible loops, an
      architecture with implications for binding affinity and function.

PMID- 23870270
TI  - Disruption of intrinsic motions as a mechanism for enzyme inhibition.
AB  - Clostridium difficile (C. diff) is one of the most common and most severe
      hospital-acquired infections; its consequences range from lengthened hospital
      stay to outright lethality. C. diff causes cellular damage through the action of
      two large toxins TcdA and TcdB. Recently, there has been increased effort toward
      developing antitoxin therapies, rather than antibacterial treatments, in hopes of
      mitigating the acquisition of drug resistance. To date, no analysis of the
      recognition mechanism of TcdA or TcdB has been attempted. Here, we use small
      molecule flexible docking followed by unbiased molecular dynamics to obtain a
      more detailed perspective on how inhibitory peptides, exemplified by two species
      HQSPWHH and EGWHAHT function. Using principal component analysis and generalized
      masked Delaunay analysis, an examination of the conformational space of TcdB in
      its apo form as well as forms bound to the peptides and UDP-Glucose was
      performed. Although both species inhibit by binding in the active site, they do
      so in two very different ways. The simulations show that the conformational space
      occupied by TcdB bound to the two peptides are quite different and provide
      valuable insight for the future design of toxin inhibitors and other enzymes that
      interact with their substrates through conformational capture mechanisms and thus
      work by the disruption of the protein's intrinsic motions.

PMID- 23870271
TI  - Platelet transport rates and binding kinetics at high shear over a thrombus.
AB  - Thrombus formation over a ruptured atherosclerotic plaque cap can occlude an
      artery with fatal consequences. We describe a computational model of platelet
      transport and binding to interpret rate-limiting steps seen in experimental
      thrombus formation over a collagen-coated stenosis. The model is used to compute
      shear rates in stenoses with growing boundaries. In the model, moving
      erythrocytes influence platelet transport based on shear-dependent enhanced
      diffusivity and a nonuniform platelet distribution. Adhesion is modeled as
      platelet-platelet binding kinetics. The results indicate that observed thrombus
      growth rates are limited by platelet transport to the wall for shear rates up to
      6000 s(-1). Above 7000 s(-1), the thrombus growth rate is likely limited by
      binding kinetics (10(-4) m/s). Thrombus growth computed from these rate-limiting
      steps match the thrombus location and occlusion times for experimental conditions
      if a lag time for platelet activation is included. Using fitted parameters, the
      model is then used to predict thrombus size and shape at a higher Reynolds number
      flow consistent with coronary artery disease. 

PMID- 23870272
TI  - Quantitative assessment of thermodynamic constraints on the solution space of
      genome-scale metabolic models.
AB  - Constraint-based methods provide powerful computational techniques to allow
      understanding and prediction of cellular behavior. These methods rely on
      physiochemical constraints to eliminate infeasible behaviors from the space of
      available behaviors. One such constraint is thermodynamic feasibility, the
      requirement that intracellular flux distributions obey the laws of
      thermodynamics. The past decade has seen several constraint-based methods that
      interpret this constraint in different ways, including those that are limited to
      small networks, rely on predefined reaction directions, and/or neglect the
      relationship between reaction free energies and metabolite concentrations. In
      this work, we utilize one such approach, thermodynamics-based metabolic flux
      analysis (TMFA), to make genome-scale, quantitative predictions about metabolite
      concentrations and reaction free energies in the absence of prior knowledge of
      reaction directions, while accounting for uncertainties in thermodynamic
      estimates. We applied TMFA to a genome-scale network reconstruction of
      Escherichia coli and examined the effect of thermodynamic constraints on the flux
      space. We also assessed the predictive performance of TMFA against gene
      essentiality and quantitative metabolomics data, under both aerobic and
      anaerobic, and optimal and suboptimal growth conditions. Based on these results,
      we propose that TMFA is a useful tool for validating phenotypes and generating
      hypotheses, and that additional types of data and constraints can improve
      predictions of metabolite concentrations. 

PMID- 23870273
TI  - Diastolic field stimulation: the role of shock duration in epicardial activation
      and propagation.
AB  - Detailed knowledge of tissue response to both systolic and diastolic shock is
      critical for understanding defibrillation. Diastolic field stimulation has been
      much less studied than systolic stimulation, particularly regarding transient
      virtual anodes. Here we investigated high-voltage-induced polarization and
      activation patterns in response to strong diastolic shocks of various durations
      and of both polarities, and tested the hypothesis that the activation versus
      shock duration curve contains a local minimum for moderate shock durations, and
      it grows for short and long durations. We found that 0.1-0.2-ms shocks produced
      slow and heterogeneous activation. During 0.8-1 ms shocks, the activation was
      very fast and homogeneous. Further shock extension to 8 ms delayed activation
      from 1.55 +/- 0.27 ms and 1.63 +/- 0.21 ms at 0.8 ms shock to 2.32 +/- 0.41 ms
      and 2.37 +/- 0.3 ms (N = 7) for normal and opposite polarities, respectively. The
      traces from hyperpolarized regions during 3-8 ms shocks exhibited four different
      phases: beginning negative polarization, fast depolarization, slow
      depolarization, and after-shock increase in upstroke velocity. Thus, the shocks
      of >3 ms in duration created strong hyperpolarization associated with significant
      delay (P < 0.05) in activation compared with moderate shocks of 0.8 and 1 ms.
      This effect appears as a dip in the activation-versus-shock-duration curve.

PMID- 23870274
TI  - Stochastic cardiac pacing increases ventricular electrical stability--a
      computational study.
AB  - The ventricular tissue is activated in a stochastic rather than in a
      deterministic rhythm due to the inherent heart rate variability (HRV). Low HRV is
      a known predictor for arrhythmia events and traditionally is attributed to
      autonomic nervous system tone damage. Yet, there is no model that directly
      assesses the antiarrhythmic effect of pacing stochasticity per se. One
      dimensional (1D) and two-dimensional (2D) human ventricular tissues were modeled,
      and both deterministic and stochastic pacing protocols were applied. Action
      potential duration restitution (APDR) and conduction velocity restitution (CVR)
      curves were generated and analyzed, and the propensity and characteristics of
      action potential duration (APD) alternans were investigated. In the 1D model,
      pacing stochasticity was found to sustain a moderating effect on the APDR curve
      by reducing its slope, rendering the tissue less arrhythmogenic. Moreover,
      stochasticity was found to be a significant antagonist to the development of
      concordant APD alternans. These effects were generally amplified with increased
      variability in the pacing cycle intervals. In addition, in the 2D tissue
      configuration, stochastic pacing exerted a protective antiarrhythmic effect by
      reducing the spatial APD heterogeneity and converting discordant APD alternans to
      concordant ones. These results suggest that high cardiac pacing stochasticity is
      likely to reduce the risk of cardiac arrhythmias in patients. 

PMID- 23870275
TI  - Quantitative analysis of three-dimensional fluorescence localization microscopy
      data.
AB  - Identifying the three-dimensional molecular organization of subcellular
      organelles in intact cells has been challenging to date. Here we present an
      analysis approach for three-dimensional localization microscopy that can not only
      identify subcellular objects below the diffraction limit but also quantify their
      shape and volume. This approach is particularly useful to map the topography of
      the plasma membrane and measure protein distribution within an undulating
      membrane.

PMID- 23870276
TI  - Domain-opening and dynamic coupling in the alpha-subunit of heterotrimeric G
      proteins.
AB  - Heterotrimeric G proteins are conformational switches that turn on intracellular
      signaling cascades in response to the activation of G-protein-coupled receptors.
      Receptor activation by extracellular stimuli promotes a cycle of GTP binding and
      hydrolysis on the G protein alpha-subunit (Galpha). Important conformational
      transitions occurring during this cycle have been characterized from extensive
      crystallographic studies of Galpha. However, the link between the observed
      conformations and the mechanisms involved in G-protein activation and effector
      interaction remain unclear. Here we describe a comprehensive principal component
      analysis of available Galpha crystallographic structures supplemented with
      extensive unbiased conventional and accelerated molecular dynamics simulations
      that together characterize the response of Galpha to GTP binding and hydrolysis.
      Our studies reveal details of activating conformational changes as well as the
      intrinsic flexibility of the alpha-helical domain that includes a large-scale 60
      degrees  domain opening under nucleotide-free conditions. This result is
      consistent with the recently reported open crystal structure of Gs, the
      stimulatory G protein for adenylyl cyclase, in complex with the alpha2 adrenergic
      receptor. Sets of unique interactions potentially important for the
      conformational transition are also identified. Moreover simulations reveal
      nucleotide-dependent dynamical couplings of distal regions and residues
      potentially important for the allosteric link between functional sites.

PMID- 23870277
TI  - Barriers and facilitating factors to the uptake of antiretroviral drugs for
      prevention of mother-to-child transmission of HIV in sub-Saharan Africa: a
      systematic review.
AB  - OBJECTIVES: To investigate and synthesize reasons for low access, initiation and
      adherence to antiretroviral drugs by mothers and exposed babies for prevention of
      mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa. METHODS: A
      systematic literature review was conducted. Four databases were searched
      (Medline, Embase, Global Health and Web of Science) for studies conducted in sub
      Saharan Africa from January 2000 to September 2012. Quantitative and qualitative
      studies were included that met pre-defined criteria. Antiretroviral (ARV)
      prophylaxis (maternal/infant) and combination antiretroviral therapy (ART)
      usage/registration at HIV care and treatment during pregnancy were included as
      outcomes. RESULTS: Of 574 references identified, 40 met the inclusion criteria.
      Four references were added after searching reference lists of included articles.
      Twenty studies were quantitative, 16 were qualitative and eight were mixed
      methods. Forty-one studies were conducted in Southern and East Africa, two in
      West Africa, none in Central Africa and one was multi-regional. The majority
      (n=25) were conducted before combination ART for PMTCT was emphasized in 2006. At
      the individual-level, poor knowledge of HIV/ART/vertical transmission, lower
      maternal educational level and psychological issues following HIV diagnosis were
      the key barriers identified. Stigma and fear of status disclosure to partners,
      family or community members (community-level factors) were the most frequently
      cited barriers overall and across time. The extent of partner/community support
      was another major factor impeding or facilitating the uptake of PMTCT ARVs, while
      cultural traditions including preferences for traditional healers and birth
      attendants were also common. Key health-systems issues included poor staff-client
      interactions, staff shortages, service accessibility and non-facility deliveries.
      CONCLUSIONS: Long-standing health-systems issues (such as staffing and service
      accessibility) and community-level factors (particularly stigma, fear of
      disclosure and lack of partner support) have not changed over time and continue
      to plague PMTCT programmes more than 10 years after their introduction. The
      potential of PMTCT programmes to virtually eliminate vertical transmission of HIV
      will remain elusive unless these barriers are tackled. The prominence of
      community-level factors in this review points to the importance of community
      driven approaches to improve uptake of PMTCT interventions, although packages of
      solutions addressing barriers at different levels will be important.

PMID- 23870278
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the
      treatment of advanced epithelial ovarian carcinoma: upfront therapy, at first
      recurrence, or later?
AB  - AIM: Cytoreductive surgery combined with hyperthermic intraperitoneal
      chemotherapy (CRS+HIPEC) has been proposed as treatment for advanced epithelial
      ovarian carcinoma (EOC). No consensus exists on when to administer CRS+HIPEC
      during the natural history of the disease, namely, as upfront therapy, at first
      recurrence, or at second or subsequent recurrence. PATIENTS AND METHODS: We
      analyzed a series of patients with advanced EOC collected prospectively in an
      institution with a peritoneal malignant disease treatment program. Patients were
      treated with CRS+HIPEC upfront, at first recurrence, and at second or subsequent
      recurrence. RESULTS: We treated 42 patients: 15 upfront, 19 at first recurrence,
      and 8 at second or subsequent recurrence. Cytoreduction was complete (CC0) in 75%
      of cases; residual disease was <2.5 mm (CC1) in 25%. Severe morbidity (CTCAE
      v.3.0, grade 3-4) was 26%, and hospital mortality was 7%. After a median follow
      up of 24 months, median overall survival was 77.8 months for patients treated
      upfront, 62.8 months for patients treated at first recurrence, and 35.7 months
      for patients treated at second or subsequent recurrence. Disease-free survival
      was 21.1 months, 18 months, and 5.7 months, respectively. Overall survival in the
      upfront and first recurrence groups was similar, and statistically significant
      differences with the second recurrence group were identified (p<0.03).
      CONCLUSIONS: Treatment of advanced EOC using CRS+HIPEC is promising in terms of
      overall survival and disease-free survival when administered as upfront and at
      first recurrence therapy. These results warrant further evaluation in a
      randomized trial.

PMID- 23870280
TI  - National suicide rates and mental health system indicators: an ecological study
      of 191 countries.
AB  - PURPOSE: The relative contributions of psychiatric morbidity and psychosocial
      stress to suicide, and the efficacy of mental health systems in reducing
      population suicide rates, are currently unclear. This study, therefore, aimed to
      investigate whether national suicide rates are associated with their
      corresponding mental health system indicators. METHODS: Relevant data were
      retrieved from the following sources: the World Health Organization, the United
      Nations Statistics Division and the Central Intelligence Agency World Fact book.
      Suicide rates of 191 countries were compared with their mental health system
      indicators using an ecological study design and multivariate non-parametric
      robust regression models. RESULTS: Significant positive correlations between
      suicide rates and mental health system indicators (p<0.001) were documented.
      After adjusting for the effects of major macroeconomic indices using multivariate
      analyses, numbers of psychiatrists (p=0.006) and mental health beds (p<0.001)
      were significantly positively associated with population suicide rates.
      CONCLUSIONS: Countries with better psychiatric services experience higher suicide
      rates. Although these associations should be interpreted with caution, as the
      issues are complex, we suggest that population-based public health strategies may
      have greater impact on national suicide rates than curative mental health
      services for individuals.

PMID- 23870279
TI  - Total glucosides of paeony prevents juxta-articular bone loss in experimental
      arthritis.
AB  - BACKGROUND: Total glucosides of paeony (TGP) is a biologically active compound
      extracted from Paeony root. TGP has been used in rheumatoid arthritis therapy for
      many years. However, the mechanism by which TGP prevents bone loss has been less
      explored. METHODS: TGP was orally administered for 3 months to New Zealand
      rabbits with antigen-induced arthritis (AIA). Digital x-ray knee images and bone
      mineral density (BMD) measurements of the subchondral knee bone were performed
      before sacrifice. Chondrocytes were observed using transmission electron
      microscopy (TEM). Histological analysis and mRNA expression of receptor activator
      of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) were evaluated in
      joint tissues. RESULTS: The BMD value in TGP rabbits was significantly higher
      compared with that seen in the AIA model rabbits. In addition, the subchondral
      bone plate was almost completely preserved by TGP treatment, while there was a
      decrease in bone plate integrity in AIA rabbits. There was less damage to the
      chondrocytes of the TGP treated group. Immunohistochemical examination of the TGP
      group showed that a higher percentage of TGP treated chondrocytes expressed OPG
      as compared to the chondrocytes isolated from AIA treated animals. In contrast,
      RANKL expression was significantly decreased in the TGP treated group compared to
      the AIA group. In support of the immunohistochemistry data, the expression of
      RANKL mRNA was decreased and OPG mRNA expression was enhanced in the TGP group
      when compared to that of the AIA model group. CONCLUSION: These results reveal
      that TGP suppresses juxta-articular osteoporosis and prevents subchondral bone
      loss. The decreased RANKL and increased OPG expression seen in TGP treated
      animals could explain how administration of TGP maintains higher BMD.

PMID- 23870281
TI  - Comparison of the Montreal Cognitive Assessment and the Mini-Mental State
      Examination in detecting multi-domain mild cognitive impairment in a Chinese sub
      sample drawn from a population-based study.
AB  - BACKGROUND: We examined the discriminant validity of the Montreal Cognitive
      Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in detecting
      multiple-domain mild cognitive impairment (md-MCI) in a Chinese sub-sample drawn
      from elderly population-based study. METHODS: This study included Chinese
      participants from the Epidemiology of Dementia in Singapore (EDIS) study aged >=
      60 years who underwent cognitive screening with the Abbreviated Mental Test and
      Progressive Forgetfulness Questionnaire. Screen-positive participants
      subsequently underwent MoCA, MMSE, and a comprehensive formal neuropsychological
      battery. MCI was defined by Petersen's criteria and further classified into
      single-domain MCI (sd-MCI) and md-MCI. Area under the receiver operating
      characteristic curve (AUC) with 95% confidence intervals (CIs) was computed for
      the MoCA and the MMSE in detecting md-MCI. RESULTS: A total of 300 participants
      were recruited: 128 (42.7%) were diagnosed with no cognitive impairment (NCI), 47
      (15.7%) with sd-MCI, and 83 (28.0%) with md-MCI. Forty-one participants were
      excluded, 7 (2.3%) had dementia, and 34 (11.3%) had only objective cognitive
      impairment without subjective complaints. Although the MoCA had a significantly
      larger AUC than the MMSE (0.94 (95% CI = 0.91-0.97) vs. 0.91 (95% CI = 0.86
      0.95), p= 0.04), at optimal cut-off points, the MoCA (19/20) was equivalent to
      the MMSE (25/26) in detecting md-MCI (sensitivity: 0.80 vs. 0.87, specificity:
      0.92 vs. 0.80). CONCLUSION: Both screening tests had good discriminant validity
      and can be used in detecting md-MCI in a sub-sample of Chinese drawn from a
      population-based study.

PMID- 23870283
TI  - The persistent plausibility of protein synthesis in the nucleus: process,
      palimpsest or pitfall?

PMID- 23870282
TI  - Differential impacts of juvenile hormone, soldier head extract and alternate
      caste phenotypes on host and symbiont transcriptome composition in the gut of the
      termite Reticulitermes flavipes.
AB  - BACKGROUND: Termites are highly eusocial insects and show a division of labor
      whereby morphologically distinct individuals specialize in distinct tasks. In the
      lower termite Reticulitermes flavipes (Rhinotermitidae), non-reproducing
      individuals form the worker and soldier castes, which specialize in helping
      (e.g., brood care, cleaning, foraging) and defense behaviors, respectively.
      Workers are totipotent juveniles that can either undergo status quo molts or
      develop into soldiers or neotenic reproductives. This caste differentiation can
      be regulated by juvenile hormone (JH) and primer pheromones contained in soldier
      head extracts (SHE). Here we offered worker termites a cellulose diet treated
      with JH or SHE for 24-hr, or held them with live soldiers (LS) or live neotenic
      reproductives (LR). We then determined gene expression profiles of the host
      termite gut and protozoan symbionts concurrently using custom cDNA oligo
      microarrays containing 10,990 individual ESTs. RESULTS: JH was the most
      influential treatment (501 total ESTs affected), followed by LS (24 ESTs), LR (12
      ESTs) and SHE treatments (6 ESTs). The majority of JH up- and downregulated ESTs
      were of host and symbiont origin, respectively; in contrast, SHE, LR and LS
      treatments had more uniform impacts on host and symbiont gene expression. Repeat
      "follow-up" bioassays investigating combined JH + SHE impacts in relation to
      individual JH and SHE treatments on a subset of array-positive genes revealed (i)
      JH and SHE treatments had opposite impacts on gene expression and (ii) JH + SHE
      impacts on gene expression were generally intermediate between JH and SHE.
      CONCLUSIONS: Our results show that JH impacts hundreds of termite and symbiont
      genes within 24-hr, strongly suggesting a role for the termite gut in JH
      dependent caste determination. Additionally, differential impacts of SHE and LS
      treatments were observed that are in strong agreement with previous studies that
      specifically investigated soldier caste regulation. However, it is likely that
      gene expression outside the gut may be of equal or greater importance than gut
      gene expression.

PMID- 23870284
TI  - Genome maintenance in the nervous system; insight into the role of the DNA damage
      response in brain development and disease.

PMID- 23870285
TI  - Collective patient behaviours derailing ART roll-out in KwaZulu-Natal:
      perspectives of health care providers.
AB  - BACKGROUND: Antiretroviral therapy (ART) roll-out is fraught with challenges,
      many with serious repercussions. We explored and described patient behaviour
      related challenges from the perspective of health care providers from non
      governmental organisations involved in ART programmes in KwaZulu-Natal, South
      Africa. METHODS: A descriptive case study design using qualitative approach was
      applied during this study. Data was collected from nine key informants from the
      three biggest NGOs involved in ART roll-out using in-depth semi-structured
      interviews. Transcribing and coding for emergent themes was done by two
      independent reviewers. Ethical approval for the study was granted by the UNISA
      research ethics committee of The Faculty of Health Sciences. Written consent was
      obtained from directors of the three NGOs involved and individual audio taped
      informed consent was obtained from all study participants prior to data
      collection. RESULTS: Findings revealed six broad areas of patient behaviour
      challenges. These were patient behaviour related to socio-economic situation of
      patient (skipping of medication due to lack of food, or due to lack of transport
      fees), belief systems (traditional and religious), stigma (non- disclosure),
      sexual practices (non-acceptability of condoms, teenage pregnancies), escapism
      (drug and alcohol abuse) and opportunism (skipping medication in order to access
      disability grant, teenage pregnancies in order to access child grant).
      CONCLUSION: New programmes need to address patient behaviour as a complex
      phenomenon requiring a multi-pronged approach that also addresses social norms
      and institutions. In the face of continued ART scale up, this is further evidence
      for the need for multi-sectoral collaboration to ensure successful and
      sustainable ART roll-out.

PMID- 23870287
TI  - Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated
      with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial.
AB  - BACKGROUND: In a simulation based on a pharmacokinetic model we demonstrated that
      increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening
      their administration interval decreases hemoglobin variability. The benefit of
      reducing the administration interval was however lessened by the variability
      induced by more frequent dosage adjustments. The purpose of this study was to
      analyze the reticulocyte and hemoglobin kinetics and variability under different
      ESAs and administration intervals in a collective of chronic hemodialysis
      patients. METHODS: The study was designed as an open-label, randomized, four
      period cross-over investigation, including 30 patients under chronic hemodialysis
      at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2
      years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and
      every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other.
      The mean square successive difference of hemoglobin, reticulocyte count and ESAs
      dose was used to quantify variability. We distinguished a short- and a long-term
      variability based respectively on the weekly and monthly successive difference.
      RESULTS: No difference was found in the mean values of biological parameters
      (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did
      not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more
      sustained reticulocytes response over time and increased the risk of hemoglobin
      overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened
      the amplitude of reticulocyte count fluctuations but resulted in more frequent
      ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability.
      Q2W administration interval was however more favorable in terms of ESAs dose,
      allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa.
      CONCLUSIONS: The reticulocyte dynamic was a more sensitive marker of time
      instability of the hemoglobin response under ESAs therapy. The ESAs
      administration interval had a greater impact on hemoglobin variability than the
      ESAs type. The more protracted reticulocyte response induced by C.E.R.A. could
      explain both, the observed higher risk of overshoot and the significant increase
      in efficacy when shortening its administration interval. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01666301.

PMID- 23870286
TI  - Green tea polyphenols alleviate early BBB damage during experimental focal
      cerebral ischemia through regulating tight junctions and PKCalpha signaling.
AB  - BACKGROUND: It has been supposed that green tea polyphenols (GTPs) have
      neuroprotective effects on brain damage after brain ischemia in animal
      experiments. Little is known regarding GTPs' protective effects against the blood
      brain barrier (BBB) disruption after ischemic stroke. We investigated the effects
      of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding
      cellular mechanisms involved in the early stage of cerebral ischemia. METHODS:
      Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for
      0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by
      intragastric gavage twice a day for 30 days prior to MCAO. At different time
      points, the expression of claudin-5, occludin, ZO-1, and PKCalpha signaling
      pathway in microvessel fragments of cerebral ischemic tissue were evaluated.
      RESULTS: GTPs reduced BBB permeability at 60 min and 120 min after ischemia as
      compared with the vehicle group. Transmission electron microscopy also revealed
      that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and
      120 min after MACO. The decreased mRNA and protein expression levels of claudin
      5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were
      significantly prevented by treatment with GTPs at the same time points after
      ischemia in rats. Furthermore, GTPs could attenuate the increase in the
      expression levels of PKCalpha mRNA and protein caused by cerebral ischemia.
      CONCLUSIONS: These results demonstrate that GTPs may act as a potential
      neuroprotective agent against BBB damage at the early stage of focal cerebral
      ischemia through the regulation of TJ and PKCalpha signaling.

PMID- 23870288
TI  - Molecular classification of the natural exudates of the rosids.
AB  - Exudates of the rosid clade of the eudicots have been surveyed and characterized
      by carbon-13 and proton nuclear magnetic resonance spectroscopy. Of 554 samples
      divided roughly equally between the subclades fabids and malvids, about two
      fifths are resins, a third gums, one-ninth gum resins, one-twelfth kinos, and the
      remaining not affiliated with these four main molecular classes. Two small new
      molecular classes, respectively from the Clusiaceae (xanthics) and the
      Zygophyllaceae (guaiacs), are identified and described. 

PMID- 23870289
TI  - Assessing adolescent preference in the treatment of first-episode psychosis and
      psychosis risk.
AB  - AIM: The objective of this study was to investigate the treatment preferences of
      adolescents with a first-episode psychosis (FEP) or at-risk mental state (ARMS)
      for psychosis. METHODS: A questionnaire was distributed to all adolescents (12-18
      years) within an early intervention in psychosis service based in North-East
      England, during a 3-month period. RESULTS: Forty eligible young people responded
      (53% response rate). The majority of FEP and ARMS participants endorsed
      psychoeducational material as the most popular treatment choice (36/40; 90%) from
      the interventions described. Participants with FEP indicated a significant
      preference for using antipsychotic medications over their ARMS counterparts (75%
      vs. 25%). CONCLUSIONS: These findings support the use of psychoeducational
      interventions (both groups) and antipsychotic medication in adolescent FEP (as
      opposed to ARMS) patient groups, albeit in a small sample requiring replication.
      This study indicates that the generation of future treatment guidelines and the
      allocation of clinical resources should be informed by patient preference where
      possible.

PMID- 23870292
TI  - [Use of ECMO (extracorporeal membrane oxygenation) in a traumatic brain injured
      patient with severe hypoxemia].
AB  - Traumatic brain injuries are fairly sensitive to hypoxia. For patient with
      associated lung and brain traumas, different means used to improve oxygen blood
      level are poorly described. We report the use of ECMO in a refractory hypoxemia
      occurred to a multitrauma young patient with neurological lesions. 

PMID- 23870293
TI  - Cooperation between physical medicine et rehabilitation journals: an overview.

PMID- 23870290
TI  - Biomarkers for determining the prognosis in chronic myelogenous leukemia.
AB  - The introduction of BCR-ABL1 tyrosine kinase inhibitors (TKIs) for treatment of
      chronic myelogenous leukemia in chronic phase (CML-CP) has revolutionized
      therapy, altering the outcome from one of shortened life expectancy to long-term
      survival. With over 10 years of long-term treatment with imatinib and several
      years of experience with the next generation of TKIs, including nilotinib,
      dasatinib, bosutinib, and ponatinib, it is becoming clear that many clinical
      parameters have great impact on the prognosis of patients with CML. Emerging
      novel gene expression profiling and molecular techniques also provide new
      insights into CML pathogenesis and have identified potential prognostic markers
      and therapeutic targets. This review presents the supporting data and discusses
      how certain clinical characteristics at diagnosis, the depth of early response,
      the presence of certain kinase domain mutations, and additional molecular changes
      serve as prognostic factors that may guide individualized treatment decisions for
      patients with CML-CP.

PMID- 23870291
TI  - Interaction of nanoparticles with proteins: relation to bio-reactivity of the
      nanoparticle.
AB  - Interaction of nanoparticles with proteins is the basis of nanoparticle bio
      reactivity. This interaction gives rise to the formation of a dynamic
      nanoparticle-protein corona. The protein corona may influence cellular uptake,
      inflammation, accumulation, degradation and clearance of the nanoparticles.
      Furthermore, the nanoparticle surface can induce conformational changes in
      adsorbed protein molecules which may affect the overall bio-reactivity of the
      nanoparticle. In depth understanding of such interactions can be directed towards
      generating bio-compatible nanomaterials with controlled surface characteristics
      in a biological environment. The main aim of this review is to summarise current
      knowledge on factors that influence nanoparticle-protein interactions and their
      implications on cellular uptake. 

PMID- 23870294
TI  - Drainage days-an independent risk factor for serious sternal wound infections
      after cardiac surgery: a case control study.
AB  - BACKGROUND: Postoperative sternal wound infections are a potentially devastating
      complication following cardiac surgery. The aim of our study was to determine
      risk factors associated with patients' baseline characteristics and peri- and
      postoperative management for the development of surgical site infections (SSIs)
      after cardiac surgery involving sternotomy. METHODS: Since 2009 the University
      Hospital of Basel, a tertiary care center in Switzerland, has participated in the
      national SSI-surveillance program by conducting postdischarge surveillance. We
      conducted a nested case-control study involving 30 consecutive patients with an
      organ/space SSI after cardiac surgery and 60 control patients. RESULTS: Receipt
      of antibiotics before operation (odds ratio [OR], 1.20; 95% confidence interval
      [CI], 1.02-1.41; P = .032), decreased albumin levels (OR, 0.87; 95% CI, 0.76
      0.99; P = .040, respectively), time on extracorporal circulation (OR, 1.02; 95%
      CI, 1.00-1.03; P = .012), number of drainages (OR, 9.15; 95% CI, 2.01-41.76; P =
      .004), length of drain retention (OR, 1.44; 95% CI, 1.10-1.90; P = .009), and
      resuscitation (OR, 7.30; 95% CI, 1.53-34.71; P = .012) were associated with SSIs.
      Incidence density drainage days-accounting for both number of drains and length
      of retention-were the only independent risk factor (OR, 1.12; 95% CI, 1.02-1.11;
      P = .018). CONCLUSIONS: Retention of drainages in the operative site longer than
      48 hours was the only independent risk factor for the development of organ/space
      sternal wound infections after cardiac surgery.

PMID- 23870295
TI  - Impact of an antimicrobial stewardship program with multidisciplinary cooperation
      in a community public teaching hospital in Taiwan.
AB  - BACKGROUND: Reports of antimicrobial stewardship programs (ASPs) in community
      hospitals are limited, with the major focus on specific agents, small settings,
      or short time periods. Here we present the outcomes of cost control, consumption
      restraint, and quality of care after a 3-year multidisciplinary ASP in a 415-bed
      community public teaching hospital. METHODS: Three strategies for improving
      antimicrobial stewardship were implemented: education, clinical pharmacists-based
      intervention, and regular outcome announcement. The steering panel of the program
      was a committee composed of infection specialists, attending physicians, clinical
      pharmacists, nurses, and medical laboratorists. RESULTS: Semiannual data from
      July 2009 to June 2012 was analyzed. Antibiotic costs declined from $21,464 to
      $12,146 per 1,000 patient-days (-43.4%). Approximately $2.5 million was saved in
      3 years, and estimated labor cost was $3,935 per month. Defined daily dose per
      1,000 patient-days were diminished from 906.7 to 717.5 (-20.9%). Significant
      reductions were found in the consumption of aminoglycosides, first-generation
      cephalosporins, and aminopenicillins. However, through comprehensive auditing,
      increasing consumption of fourth-generation cephalosporins and fluoroquinolones
      was noticed. No significant difference in the quality of care (ie, length of
      stay, incidence of health care associated infections, and mortality) was
      observed. CONCLUSIONS: The multidisciplinary ASP was beneficial to reduce
      antibiotic cost and consumption. The strategies were practical and worthy to be
      recommended to community health care settings.

PMID- 23870296
TI  - Risk factors for acquisition of multidrug-resistant Acinetobacter baumannii among
      cancer patients.
AB  - BACKGROUND: Data regarding multidrug-resistant (MDR) Acinetobacter baumannii
      infections among cancer patients are limited. METHODS: We conducted a case
      control study to investigate the risk factors for acquisition of MDR A baumannii
      and the outcomes among cancer patients. Cases were inpatients with malignancy who
      had MDR A baumannii from any cultures between 2008 and 2011. Controls were
      inpatients with malignancy but no MDR A baumannii. RESULTS: A total of 31 case
      patients were matched with 62 control patients. Hematologic malignancy (P =
      .036), need for dialysis (P = .01), admission for other reasons except elective
      surgery (P = .03), transfer from other health care facilities (P = .02),
      prolonged intensive care unit stay (P = .004), mechanical ventilation (P < .001),
      pressor use (P = .001), tube feeding (P < .001), transfusion (P = .009), and
      prior antimicrobial use (P < .001) were identified as significant risk factors in
      univariate analysis. Need for dialysis (odds ratio [OR], 18.23; P = .04) and
      prolonged intensive care unit stay (OR, 19.28; P = .01) remained significant in
      multivariate analysis. Lengths of stay were 28 days for the case patients and 10
      days for the control patients (P = .001). The 90-day mortality rates were 41.9%
      and 29.0%, respectively (P = .20). CONCLUSIONS: Acquisition of MDR A baumannii
      among cancer patients appears to be associated with general nosocomial infection
      risk factors rather than underlying malignancies.

PMID- 23870297
TI  - Program evaluation of a telepsychiatry service for older adults connecting a
      university-affiliated geriatric center to a rural psychogeriatric outreach
      service in Northwest Ontario, Canada.
AB  - BACKGROUND: Weekly telepsychiatry consultations have been provided since 2002 to
      six communities in Northwest Ontario. Staff from a single community
      psychogeriatric outreach service who work within these communities facilitate the
      referrals. METHODS: The program evaluation included (a) a chart review of the
      last 100 referrals, (b) analysis of patient and staff evaluations, (c) a survey
      mailed to all physicians in referring communities, and (d) three focus groups of
      staff working in local community agencies. RESULTS: The mean age at the time of
      consultation was 76.7 years. Sixty-eight percent of patients were females. The
      most frequent diagnoses were dementia (54%), depression (28%), and mild cognitive
      impairment (19%). The most frequent medication recommendations were
      antidepressants or cholinesterase inhibitors. Two hundred ninety-four patient
      assessments and case consultations were carried out between 2002 and 2009. Post
      session evaluation surveys rated the provision of information, whether objectives
      were met, and overall usefulness of recommendations. The mean scores for these
      questions on a 5-point scale were between 4.6 and 4.85. Referring physicians were
      confident and satisfied with the recommendations made for their patients. All
      planned to continue to use telepsychiatry as a care option for the future. The
      focus groups added useful information about challenges and potential barriers to
      utilizing the program. CONCLUSIONS: The program was rated as being highly valued
      across all modalities of evaluation. Members of the referring team believe that
      access to a geriatric psychiatrist has broadened the team's knowledge base, its
      use of assessment tools, and increased their ability to better construct their
      patients' treatment plans.

PMID- 23870298
TI  - Mammary hypoplasia: not every breast can produce sufficient milk.
AB  - Breast milk is considered the optimal form of nutrition for newborn infants.
      Current recommendations are to breastfeed for 6 months. Not all women are able to
      breastfeed. Mammary hypoplasia is a primary cause of failed lactogenesis II,
      whereby the mother is unable to produce an adequate milk volume. Women with
      mammary hypoplasia often have normal hormone levels and innervation but lack
      sufficient glandular tissue to produce an adequate milk supply to sustain their
      infant. The etiology of this rare condition is unclear, although there are
      theories that refer to genetic predisposition and estrogenic environmental
      exposures in select agricultural environments. Women with mammary hypoplasia may
      not exhibit the typical breast changes associated with pregnancy and may fail to
      lactate postpartum. Breasts of women with mammary hypoplasia may be widely spaced
      (1.5 inches or greater), asymmetric, or tuberous in nature. Awareness of the
      history and clinical signs of mammary hypoplasia during the prenatal period and
      immediate postpartum increases the likelihood that women will receive the needed
      education and physical and emotional support and encouragement. Several
      medications and herbs demonstrate some efficacy in increasing breast milk
      production in women with mammary hypoplasia. 

PMID- 23870299
TI  - Reproducibility of graft preparations in Descemet's membrane endothelial
      keratoplasty.
AB  - PURPOSE: To assess the reproducibility of manual graft preparation and evaluate
      the incidence rate and nature of structural anomalies of Descemet's membrane (DM)
      preventing successful graft preparation in DM endothelial keratoplasty (DMEK).
      DESIGN: Prospective, single-center, nonrandomized, consecutive case series.
      PARTICIPANTS: We analyzed 350 corneoscleral buttons from donors aged 18-95 years
      stored in Optisol-GS or Dulbecco's modified Eagle's medium and used for DMEK
      surgery in 343 consecutive patients with Fuchs' endothelial dystrophy or
      pseudophakic bullous keratopathy. METHODS: Residual endothelial cell-DM complexes
      obtained after successful DM stripping for DMEK and whole donor corneas obtained
      after unsuccessful DM stripping were examined by transmission electron microscopy
      and immunohistochemistry. MAIN OUTCOME MEASURES: Accuracy of the cleavage plane
      between DM and corneal stroma and structural abnormalities of the DM-stroma
      interface. RESULTS: Uneventful manual separation without any disruption of DM was
      achieved in 335 of 350 donor corneas (95.7%) by use of a previously established
      bimanual submerged preparation technique. Correspondingly, the peeled DM
      specimens revealed a regular and smooth cleavage plane exposing the amorphous
      interfacial matrix on their anterior surface. Although 8 of 350 donor corneas
      (2.3%) showed focal adhesions of DM to the corneal stroma and developed isolated
      tears during stripping, preparation of the graft could be successfully completed.
      However, 7 of the 350 donor corneas (2.0%) showed extremely strong adhesion and
      multiple tears of DM, preventing successful preparation of the graft. These
      specimens revealed either ultrastructural (peg-like interlockings) or biochemical
      abnormalities (increased staining intensities for adhesive glycoproteins) along
      the DM-stroma interface. CONCLUSIONS: Using an appropriate technique, manual
      preparation of grafts for DMEK with reproducible tissue qualities is possible in
      the vast majority (98%) of donor corneas. Although a relatively rare phenomenon,
      interindividual variations in DM structure and composition may be responsible for
      failure of graft preparation in about 2% of donor corneas. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any of
      the materials discussed in this article.

PMID- 23870300
TI  - Influence of the vitreomacular interface on outcomes of ranibizumab therapy in
      neovascular age-related macular degeneration.
AB  - PURPOSE: To investigate the influence of the vitreomacular interface (VMI) on the
      functional and anatomic efficacy of ranibizumab therapy in patients with
      neovascular age-related macular degeneration (AMD). DESIGN: Subanalysis of a
      prospective, 12-month, multicenter, phase IIIb trial. PARTICIPANTS: A total of
      353 treatment-naive patients with subfoveal choroidal neovascularization (CNV)
      receiving quarterly or monthly ranibizumab therapy. METHODS: On monthly optical
      coherence tomography (OCT) scan sets, the VMI configuration was graded by a
      certified reading center into one of the following conditions: continuous
      posterior vitreoretinal attachment (PVA), vitreomacular adhesion (VMA), partial
      vitreous detachment without vitreomacular contact, or complete posterior vitreous
      detachment (PVD). Best-corrected visual acuity (BCVA) and central retinal
      thickness (CRT) measurements were performed at monthly intervals. Analysis
      included patients with a minimum of 10 OCT examinations, including baseline and
      month 12 (n = 251). After integration of the VMI configuration over 12 months,
      patients were divided into one of the following categories: PVD (n = 162),
      release of vitreomacular contact (RELEASE; n = 48), VMA (n = 37), or PVA (n = 4).
      General estimation equation analyses were applied to test for noninferiority of
      quarterly versus monthly treatment. MAIN OUTCOME MEASURES: The BCVA and CRT
      changes at month 12. RESULTS: Mean BCVA changes in letters were +4.7 (PVD), +3.2
      (RELEASE), and -0.2 (VMA) in the quarterly regimen and +4.9 (PVD), +12.7
      (RELEASE), and +7.5 (VMA) in the monthly regimen. No difference in therapeutic
      efficiency between monthly and quarterly intervention was found in eyes with PVD,
      and quarterly treatment was noninferior to monthly treatment (P = 0.001).
      However, monthly treatment was superior to quarterly treatment in the RELEASE (P
      = 0.008) and VMA (P = 0.043) groups. Mean CRT changes were -98 and -96 MUm (PVD),
      -117 and -136 MUm (RELEASE), and -93 and -87 MUm (VMA) in the monthly and
      quarterly regimens, respectively, without statistically significant differences.
      CONCLUSIONS: The configuration of the VMI seems to have an important effect on
      visual outcomes and need for retreatment. In patients with PVD, a lower treatment
      frequency may be feasible, whereas patients with RELEASE or VMA may benefit from
      intensive retreatment. These findings may serve as a basis for individualized
      treatment decisions in anti-angiogenic therapy of neovascular AMD and perhaps
      other indications.

PMID- 23870301
TI  - Myopic maculopathy imaged by optical coherence tomography: the beijing eye study.
AB  - PURPOSE: To examine the features of myopia-related optical coherence tomography
      (OCT) findings in a population-based setting. DESIGN: Population-based study.
      PARTICIPANTS: The Beijing Eye Study 2011 included 3468 subjects with an age of 50
      years or more. METHODS: The participants underwent a detailed ophthalmic
      examination including OCT with enhanced depth imaging of the macula. MAIN OUTCOME
      MEASURES: Optical coherence tomography features of the macula in highly myopic
      eyes defined by a refractive error of -6 diopters or less or an axial length of
      26.5 mm or more. RESULTS: Readable OCT images were available for 6530 eyes
      (94.5%) of 3278 participants. The most common change in the macula was
      maculoschisis (0.8+/-0.1%), followed by incomplete posterior vitreous detachment
      (0.7+/-0.1%), disruption of the photoreceptor inner segment/outer segment
      interface (0.6+/-0.1%), epiretinal membranes (0.6+/-0.1%), macular defects in
      Bruch's membrane (0.3+/-0.1%), clumping of the retinal pigment epithelium (0.2+/
      0.1%), vitreofoveal adhesion (0.2+/-0.1%), and macular holes in 2 eyes (0.1+/
      0.1%). Prevalence of any myopic maculopathy per eye was 112 of 6530, or 1.71+/
      0.16% (95% confidence interval [CI], 1.40-2.03). After adjustment for longer
      axial length (P<0.001; odds ratio [OR], 2.68; 95% CI, 1.97-3.64) and myopic
      refractive error (P<0.001; OR, 0.63; 95% CI, 0.55-0.73), presence of any myopic
      maculopathy was not significantly associated with any systemic variables (all
      P>=0.05), including biochemical blood examination and ocular parameters. Best
      corrected visual acuity was associated significantly with the absence of a
      disruption of the photoreceptor inner segment/outer segment interface (P<0.001),
      epiretinal membranes (P<0.001), and macular holes (P<0.001) after adjustment for
      age and cylindrical refractive error. CONCLUSIONS: Based on OCT examination, the
      most common macular change in highly myopic eyes was maculoschisis, followed by
      incomplete posterior vitreous detachment, disruption of the photoreceptor inner
      segment/outer segment interface, epiretinal membranes, macular defects in Bruch's
      membrane, clumping of the retinal pigment epithelium, vitreofoveal adhesion, and
      macular holes. The most important macular changes with a negative effect on best
      corrected visual acuity were a disruption of the photoreceptor inner
      segment/outer segment interface and epiretinal membranes.

PMID- 23870302
TI  - Ten-year results of a randomized controlled trial comparing 0.02% mitomycin C and
      limbal conjunctival autograft in pterygium surgery.
AB  - OBJECTIVE: To compare the long-term outcome of pterygium surgery and the long
      term effect on endothelial counts after mitomycin C (MMC) or limbal conjunctival
      autograft (LCAU) in pterygium surgery. DESIGN: We performed a 10-year follow-up
      study of a randomized controlled trial. PARTICIPANTS: A total of 115 eyes of 114
      patients with primary pterygium were treated with intraoperative MMC (n = 63) or
      LCAU transplants (n = 52). A total of 76 patients completed the current 10-year
      long-term follow-up (47 in the MMC group, 29 in the LCAU group). METHODS: This is
      a follow-up study of a randomized controlled trial of a cohort of 114 patients in
      2 groups that was performed at the Prince of Wales Hospital 10 years ago: group
      1, intraoperative 0.02% MMC for 5 minutes; group 2, LCAU. Consecutive patients
      enrolled in the original study (recruitment began in February 2001) were invited
      back for a detailed clinical examination to document the long-term outcome of
      both surgical groups. MAIN OUTCOME MEASURES: The main outcome measures included
      the recurrence rate, residual conjunctival bed status, complications, and corneal
      endothelial cell density (ECD) differences. RESULTS: A total of 115 eyes of 114
      patients were enrolled and randomized in our previous study. For the current
      study, 76 of the 114 patients (47 in the MMC group, 29 in the LCAU group) were
      contacted, whereas 18 patients were lost to follow-up and 20 patients had died.
      The mean follow-up period was 138 +/- 2 months in the MMC group and 137 +/- 2
      months in the LCAU group. Twelve of 47 patients (25.5%) in the original MMC group
      and 2 of 29 patients (6.9%) in the LCAU group had recurrent pterygium (P =
      0.021). The mean ECD was 2,39 2 +/- 342 cells/mm(2) in the MMC group and 2,390 +/
      388 cells/mm(2) in the LCAU group (P = 0.978). There was no significant
      difference in the ECD between the operated eyes and the fellow eyes in both
      groups (P = 0.926 MMC, P = 0.468 LCAU). No other significant ocular complications
      were observed in either group at the 10-year postoperative follow-up.
      CONCLUSIONS: Limbal conjunctival autograft was more effective than intraoperative
      MMC in minimizing pterygium recurrence at the 10-year follow-up. Treatment with
      intraoperative MMC was not associated with long-term corneal endothelial cell
      loss.

PMID- 23870303
TI  - Approach for the use of MSW settlement predictions in the assessment of landfill
      capacity based on reliability analysis.
AB  - In the analysis and design of municipal solid waste (MSW) landfills, there are
      many uncertainties associated with the properties of MSW during and after MSW
      placement. Several studies are performed involving different laboratory and field
      tests to understand the complex behavior and properties of MSW, and based on
      these studies, different models are proposed for the analysis of time dependent
      settlement response of MSW. For the analysis of MSW settlement, it is very
      important to account for the variability of model parameters that reflect
      different processes such as primary compression under loading, mechanical creep
      and biodegradation. In this paper, regression equations based on response surface
      method (RSM) are used to represent the complex behavior of MSW using a newly
      developed constitutive model. An approach to assess landfill capacities and
      develop landfill closure plans based on prediction of landfill settlements is
      proposed. The variability associated with model parameters relating to primary
      compression, mechanical creep and biodegradation are used to examine their
      influence on MSW settlement using reliability analysis framework and influence of
      various parameters on the settlement of MSW are estimated through sensitivity
      analysis. 

PMID- 23870304
TI  - Feasibility of scenario-based simulation training versus traditional workshops in
      continuing medical education: a randomized controlled trial.
AB  - INTRODUCTION: Although simulation-based training is increasingly used for medical
      education, its benefits in continuing medical education (CME) are less
      established. This study seeks to evaluate the feasibility of incorporating
      simulation-based training into a CME conference and compare its effectiveness
      with the traditional workshop in improving knowledge and self-reported
      confidence. METHODS: Participants (N=27) were group randomized to either a
      simulation-based workshop or a traditional case-based workshop. RESULTS: Post
      training, knowledge assessment score neither did increase significantly in the
      traditional group (d=0.13; p=0.76) nor did significantly decrease in the
      simulation group (d= - 0.44; p=0.19). Self-reported comfort in patient assessment
      parameters increased in both groups (p<0.05 in all). However, only the simulation
      group reported an increase in comfort in patient management (d=1.1, p=0.051 for
      the traditional group and d=1.3; p= 0.0003 for the simulation group). At 1 month,
      comfort measures in the traditional group increased consistently over time while
      these measures in the simulation group increased post-workshop but decreased by 1
      month, suggesting that some of the effects of training with simulation may be
      short lived. DISCUSSION: The use of simulation-based training was not associated
      with benefits in knowledge acquisition, knowledge retention, or comfort in
      patient assessment. It was associated with superior outcomes in comfort in
      patient management, but this benefit may be short-lived. Further studies are
      required to better define the conditions under which simulation-based training is
      beneficial.

PMID- 23870305
TI  - The give and take of host-microbe symbioses.
AB  - Studying the association between mealybugs and two bacterial symbionts, Husnik et
      al. (2013) demonstrated that both integration of metabolic pathways across the
      partners' genomes and horizontal gene transfer from diverse bacteria into the
      insect host genome are integral to symbiosis. 

PMID- 23870306
TI  - Intestinal irony: how probiotic bacteria outcompete bad bugs.
AB  - In this issue of Cell Host & Microbe, Deriu et al. present a mechanistic
      explanation underlying the benefits of certain probiotic bacteria. Intestinal
      bacteria compete for the essential nutrient iron, leading to replacement of
      pathogenic Salmonella by the probiotic Escherichia coli Nissle, which is better
      equipped with iron acquisition systems, and resolution of infectious colitis. 

PMID- 23870307
TI  - Balance of power in host-virus arms races.
AB  - The sensing of viral RNA by the host innate immune system is mediated by RIG-I
      and its partner PACT. In this issue of Cell Host & Microbe, Luthra et al. (2013)
      show that the Ebola virus VP35 protein counteracts the action of PACT at the cost
      of compromising its own function in viral replication. 

PMID- 23870308
TI  - Greasing the SCIDs for universal flu antibodies.
AB  - In this issue, Nakamura et al. (2013) describe a robust SCID mouse-based method
      for isolating human monoclonal antibodies of desired specificity from adoptively
      transferred human B cells. As proof of principle, they isolate human mAbs that
      could potentially be used to treat or prevent human infection with any influenza
      A virus strain. 

PMID- 23870309
TI  - Revisiting caspase-11 function in host defense.
AB  - Proinflammatory caspases play important roles in innate immunity. Much attention
      has focused on caspase-1, which acts to eliminate pathogens by obliterating their
      replicative niches as well as alerting the host to their presence. Now, emerging
      data have shed light on the lesser-studied proinflammatory caspase-11 in the
      combat between host and pathogens. Using the new tools available, researchers are
      further elucidating the mechanisms by which caspase-11 contributes to host
      defense. Here, we review the emerging understanding of caspase-11 functions and
      the mechanisms of activation and discuss the implications for human disease. 

PMID- 23870310
TI  - Leishmania evades host immunity by inhibiting antigen cross-presentation through
      direct cleavage of the SNARE VAMP8.
AB  - During phagocytosis, microorganisms are taken up by immune cells into phagosomes.
      Through membrane-trafficking events mediated by SNARE proteins, phagosomes fuse
      with lysosomes, generating degradative phagolysosomes. Phagolysosomes contribute
      to host immunity by linking microbial killing within these organelles with
      antigen processing for presentation on MHC class I or II molecules to T cells. We
      show that the intracellular parasite Leishmania evades immune recognition by
      inhibiting phagolysosome biogenesis. The Leishmania cell surface metalloprotease
      GP63 cleaves a subset of SNAREs, including VAMP8. GP63-mediated VAMP8
      inactivation or Vamp8 disruption prevents the NADPH oxidase complex from
      assembling on phagosomes, thus altering their pH and degradative properties.
      Consequently, the presentation of exogenous Leishmania antigens on MHC class I
      molecules, also known as cross-presentation, is inhibited, resulting in reduced T
      cell activation. These findings indicate that Leishmania subverts immune
      recognition by altering phagosome function and highlight the importance of VAMP8
      in phagosome biogenesis and antigen cross-presentation. 

PMID- 23870312
TI  - The Legionella effector RidL inhibits retrograde trafficking to promote
      intracellular replication.
AB  - The bacteria causing Legionnaires' disease, Legionella pneumophila, replicate
      intracellularly within unique Legionella-containing vacuoles (LCVs). LCV
      formation involves a type IV secretion system (T4SS) that translocates effector
      proteins into host cells. We show that the T4SS effector RidL localizes to LCVs,
      supports intracellular bacterial growth, and alters retrograde trafficking, in
      which selected proteins are transported from endosomes to the Golgi. The retromer
      complex that mediates retrograde trafficking localizes to LCVs independently of
      RidL and restricts intracellular bacterial growth. RidL binds the Vps29 retromer
      subunit and the lipid PtdIns(3)P, which localizes retromer components to
      membranes. Additionally, specific retromer cargo receptors and sorting nexins
      that mediate protein capture and membrane remodeling preferentially localize to
      LCVs in the absence of ridL. Ectopic RidL production inhibits retrograde
      trafficking, and L. pneumophila blocks retrograde transport at endosome exit
      sites in a ridL-dependent manner. Collectively, these findings suggest that RidL
      inhibits retromer function to promote intracellular bacterial replication. 

PMID- 23870311
TI  - Probiotic bacteria reduce salmonella typhimurium intestinal colonization by
      competing for iron.
AB  - Host inflammation alters the availability of nutrients such as iron to limit
      microbial growth. However, Salmonella enterica serovar Typhimurium thrives in the
      inflamed gut by scavenging for iron with siderophores. By administering
      Escherichia coli strain Nissle 1917, which assimilates iron by similar
      mechanisms, we show that this nonpathogenic bacterium can outcompete and reduce
      S. Typhimurium colonization in mouse models of acute colitis and chronic
      persistent infection. This probiotic activity depends on E. coli Nissle iron
      acquisition, given that mutants deficient in iron uptake colonize the intestine
      but do not reduce S. Typhimurium colonization. Additionally, the ability of E.
      coli Nissle to overcome iron restriction by the host protein lipocalin 2, which
      counteracts some siderophores, is essential, given that S. Typhimurium is
      unaffected by E. coli Nissle in lipocalin 2-deficient mice. Thus, iron
      availability impacts S. Typhimurium growth, and E. coli Nissle reduces S.
      Typhimurium intestinal colonization by competing for this limiting nutrient. 

PMID- 23870313
TI  - Vaccinia virus F11 promotes viral spread by acting as a PDZ-containing
      scaffolding protein to bind myosin-9A and inhibit RhoA signaling.
AB  - The vaccinia F11 protein promotes viral spread by modulating the cortical actin
      cytoskeleton by inhibiting RhoA signaling via an unknown mechanism. PDZ domains
      are widely conserved protein interaction modules whose occurrence in viral
      proteins is unprecedented. We found that F11 contains a central PDZ-like domain
      that is required to downregulate RhoA signaling and enhance viral spread. The PDZ
      like domain interacts with the PDZ binding motif of the Rho GTPase-activating
      protein (GAP) Myosin-9A. In the absence of Myosin-9A, RhoA signaling is not
      inhibited, resulting in fewer actin tails and reduced virus release concomitant
      with less viral spread. The loss of Myosin-9A GAP activity or its ability to bind
      F11 also reduces actin tail formation. Furthermore, the ability of Myosin-9A to
      promote viral spread depends on F11 binding RhoA. Thus, F11 acts as a functional
      PDZ-containing scaffolding protein to inhibit RhoA signaling by binding Myosin
      9A. 

PMID- 23870314
TI  - Pathogens use structural mimicry of native host ligands as a mechanism for host
      receptor engagement.
AB  - A pathogen's ability to engage host receptors is a critical determinant of its
      host range and interspecies transmissibility, key issues for understanding
      emerging diseases. However, the identification of host receptors, which are also
      attractive drug targets, remains a major challenge. Our structural bioinformatics
      studies reveal that both bacterial and viral pathogens have evolved to
      structurally mimic native host ligands (ligand mimicry), thus enabling engagement
      of their cognate host receptors. In contrast to the structural homology, amino
      acid sequence similarity between pathogen molecules and the mimicked host ligands
      was low. We illustrate the utility of this concept to identify pathogen receptors
      by delineating receptor tyrosine kinase Axl as a candidate receptor for the
      polyomavirus SV40. The SV40-Axl interaction was validated, and its participation
      in the infection process was verified. Our results suggest that ligand mimicry is
      widespread, and we present a quick tool to screen for pathogen-host receptor
      interactions. 

PMID- 23870315
TI  - Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator
      PACT determines infection outcome.
AB  - The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and
      induces type I IFN responses to control viral replication. The cellular dsRNA
      binding protein PACT can also activate RIG-I. To counteract innate antiviral
      responses, some viruses, including Ebola virus (EBOV), encode proteins that
      antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced
      RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with
      RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to
      bind PACT. In addition, PACT-VP35 interaction impairs the association between
      VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and
      modulating EBOV replication. PACT-deficient cells are defective in IFN induction
      and are insensitive to VP35 function. These data support a model in which the
      VP35-PACT interaction is mutually antagonistic and plays a fundamental role in
      determining the outcome of EBOV infection. 

PMID- 23870316
TI  - Gene loss and adaptation to hominids underlie the ancient origin of HIV-1.
AB  - HIV-1 resulted from cross-species transmission of SIVcpz, a simian
      immunodeficiency virus that naturally infects chimpanzees. SIVcpz, in turn, is a
      recombinant between two SIV lineages from Old World monkeys. Lentiviral
      interspecies transmissions are partly driven by the evolution and capacity of
      viral accessory genes, such as vpx, vpr, and vif, to antagonize host antiviral
      factors, such as SAMHD1 and the APOBEC3 proteins. We show that vpx, which in
      other lentiviruses antagonizes SAMHD1, was deleted during the creation of SIVcpz.
      This genomic deletion resulted in the reconstruction of the overlapping vif gene
      by "overprinting," creating a unique vif that overlaps in its 3' end with the vpr
      gene and can antagonize hominid APOBEC3s. Moreover, passage of SIVs through
      chimpanzees facilitated the subsequent adaptation of HIV-1 to humans. Thus, HIV-1
      originated through a series of gene loss and adaptation events that generated its
      chimpanzee precursor and lowered the species barrier to human infection. 

PMID- 23870317
TI  - An in vivo human-plasmablast enrichment technique allows rapid identification of
      therapeutic influenza A antibodies.
AB  - Recent advances enabling the cloning of human immunoglobulin G genes have proven
      effective for discovering monoclonal antibodies with therapeutic potential.
      However, these antibody-discovery methods are often arduous and identify only a
      few candidates from numerous antibody-secreting plasma cells or plasmablasts. We
      describe an in vivo enrichment technique that identifies broadly neutralizing
      human antibodies with high frequency. For this technique, human peripheral blood
      mononuclear cells from vaccinated donors are activated and enriched in an antigen
      specific manner for the production of numerous antigen-specific plasmablasts.
      Using this technology, we identified four broadly neutralizing influenza A
      antibodies by screening only 840 human antibodies. Two of these antibodies
      neutralize every influenza A human isolate tested and perform better than the
      current anti-influenza A therapeutic, oseltamivir, in treating severe influenza
      infection in mice and ferrets. Furthermore, these antibodies elicit robust in
      vivo synergism when combined with oseltamivir, thus highlighting treatment
      strategies that could benefit influenza-infected patients. 

PMID- 23870319
TI  - A systematic evaluation of hybridization-based mouse exome capture system.
AB  - BACKGROUND: Exome sequencing is increasingly used to search for phenotypically
      relevant sequence variants in the mouse genome. All of the current hybridization
      based mouse exome capture systems are designed based on the genome reference
      sequences of the C57BL/6 J strain. Given that the substantial sequence divergence
      exists between C57BL/6 J and other distantly-related strains, the impact of
      sequence divergence on the efficiency of such capture systems needs to be
      systematically evaluated before they can be widely applied to the study of those
      strains. RESULTS: Using the Agilent SureSelect mouse exome capture system, we
      performed exome sequencing on F1 generation hybrid mice that were derived by
      crossing two divergent strains, C57BL/6 J and SPRET/EiJ. Our results showed that
      the C57BL/6 J-based probes captured the sequences derived from C57BL/6 J alleles
      more efficiently and that the bias was higher for the target regions with greater
      sequence divergence. At low sequencing depths, the bias also affected the
      efficiency of variant detection. However, the effects became negligible when
      sufficient sequencing depth was achieved. CONCLUSION: Sufficient sequence depth
      needs to be planned to match the sequence divergence between C57BL/6 J and the
      strain to be studied, when the C57BL/6 J-based Agilent SureSelect exome capture
      system is to be used.

PMID- 23870318
TI  - A microscale human liver platform that supports the hepatic stages of Plasmodium
      falciparum and vivax.
AB  - The Plasmodium liver stage is an attractive target for the development of
      antimalarial drugs and vaccines, as it provides an opportunity to interrupt the
      life cycle of the parasite at a critical early stage. However, targeting the
      liver stage has been difficult. Undoubtedly, a major barrier has been the lack of
      robust, reliable, and reproducible in vitro liver-stage cultures. Here, we
      establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in
      a microscale human liver platform composed of cryopreserved, micropatterned human
      primary hepatocytes surrounded by supportive stromal cells. Using this system, we
      have successfully recapitulated the full liver stage of P. falciparum, including
      the release of infected merozoites and infection of overlaid erythrocytes, as
      well as the establishment of small forms in late liver stages of P. vivax.
      Finally, we validate the potential of this platform as a tool for medium
      throughput antimalarial drug screening and vaccine development. 

PMID- 23870320
TI  - Delay-dependent global exponential robust stability for delayed cellular neural
      networks with time-varying delay.
AB  - This paper investigates a class of delayed cellular neural networks (DCNN) with
      time-varying delay. Based on the Lyapunov-Krasovski functional and integral
      inequality approach (IIA), a uniformly asymptotic stability criterion in terms of
      only one simple linear matrix inequality (LMI) is addressed, which guarantees
      stability for such time-varying delay systems. This LMI can be easily solved by
      convex optimization techniques. Unlike previous methods, the upper bound of the
      delay derivative is taken into consideration, even if larger than or equal to 1.
      It is proven that results obtained are less conservative than existing ones. Four
      numerical examples illustrate efficacy of the proposed methods. 

PMID- 23870321
TI  - Simulator for a packing and weighing system of granulated powders.
AB  - The development of a simulator for a packing and weighing system (PWS) of
      granulated powder is described. It employed system identification to obtain the
      deterministic part of the model and stochastic processes to reproduce
      disturbances. It reproduces the fluctuations in carton weight observed in real
      packing systems. Its final use is to evaluate proposed improvements in the PWS,
      aiming at reducing overweight and underweight. Its performance is satisfactory,
      as the oscillations observed in the carton weights, due to powder density
      variability, are close to reality as well as the monetary losses due to
      overweight and underweight and the power spectral density graphs of the real and
      simulated weights. 

PMID- 23870322
TI  - Historical perspectives of The American Association for Thoracic Surgery: Thomas
      B. Ferguson (1923-2013).

PMID- 23870323
TI  - Risk factor analysis of locoregional recurrence after sublobar resection in
      patients with clinical stage IA non-small cell lung cancer.
AB  - OBJECTIVE: Although lobectomy is the standard surgical procedure for operable non
      small cell lung cancer (NSCLC), sublobar resection also has been undertaken for
      various reasons. The aim of this study was to identify risk factors of
      locoregional recurrence and poor disease-specific survival in patients with
      clinical stage IA NSCLC undergoing sublobar resection. METHODS: We
      retrospectively reviewed 328 patients with clinical stage IA NSCLC who underwent
      segmentectomy or wedge resection. Demographic, clinical, and pathologic factors
      were analyzed using the log-rank test as univariate analyses, and all factors
      were entered into a Cox proportional hazards regression model for multivariate
      analyses to identify independent predictors of locoregional recurrence and poor
      disease-specific survival. RESULTS: The 5- and 10-year locoregional recurrence
      free probabilities were 84.8% and 83.6%, respectively, and the 5- and 10-year
      disease-specific survivals were 83.6% and 73.6%, respectively. Four independent
      predictors of locoregional recurrence were identified: wedge resection (hazard
      ratio [HR], 5.787), microscopic positive surgical margin (HR, 3.888), visceral
      pleural invasion (HR, 2.272), and lymphatic permeation (HR, 3.824). Independent
      predictors of poor disease-specific survival were identified as follows: smoking
      status (Brinkman Index; HR, 1.001), wedge resection (HR, 3.183), microscopic
      positive surgical margin (HR, 3.211), visceral pleural invasion (HR, 2.553), and
      lymphatic permeation (HR, 3.223). All 4 predictors of locoregional recurrence
      also were identified as independent predictors of poor disease-specific survival.
      CONCLUSIONS: Segmentectomy should be the surgical procedure of first choice in
      patients with clinical stage IA NSCLC who are being considered for sublobar
      resection. Patients having tumors presenting with no suspicious of pleural
      involvement would be suitable candidates for sublobar resection.

PMID- 23870324
TI  - Continuous renal replacement therapy in children after cardiac surgery.
AB  - OBJECTIVE: The objective was to study the clinical course of children requiring
      continuous renal replacement therapy (CRRT) after cardiac surgery and to analyze
      the factors associated with mortality. METHODS: A prospective observational study
      was performed that included all children requiring CRRT after cardiac surgery,
      comparing these patients with other critically ill children requiring CRRT.
      Univariate and multivariate analyses were performed to determine the influence of
      each factor on mortality. RESULTS: Eighty-one (4.9%) of 1650 children undergoing
      cardiac surgery required CRRT; 65 of them (80.2%) presented multiorgan failure.
      Children starting CRRT after cardiac surgery had lower mean arterial pressure and
      lower urea and creatinine levels, and were more likely to require mechanical
      ventilation than other children on CRRT. The incidence of complications was
      similar. Cardiac surgery increased the probability of requiring CRRT for more
      than 14 days. Mortality was 43% in children receiving CRRT after cardiac surgery
      and 29% in other children (P = .05). Factors associated with mortality in the
      univariate analysis were age less than 12 months, weight less than 10 kg, higher
      Pediatric Risk of Mortality Score, hypotension, lower urea and creatinine on
      starting CRRT, and use of hemofiltration. In the multivariate analysis, the only
      factor associated with mortality was hypotension on starting CRRT (hazard ratio,
      4.01; 95% confidence interval, 1.2-13.4; P = .024). CONCLUSIONS: Although only a
      small percentage of children undergoing cardiac surgery required CRRT, mortality
      in these patients was high. Hypotension at the time of starting the technique was
      the only factor associated with a higher mortality.

PMID- 23870325
TI  - Anatomic and flow dynamic considerations for safe right axillary artery
      cannulation.
AB  - OBJECTIVES: Neuroprotection is of paramount interest in cardiac surgery. Right
      axillary artery cannulation is well established in aortic surgery because it
      significantly improves survival and outcome, but malperfusion of the right brain
      after direct cannulation has been reported. Anatomically, 4 vessel segments are
      potentially amenable for cannulation of the subclavian and axillary arteries.
      Clinical studies vary widely in dissection sites and cannulation techniques. We
      investigated critical flow dynamics in the right brain caused by arterial inflow
      after direct cannulation and specified cannulation positions that provide optimal
      cerebral perfusion. METHODS: Distances from the lateral margin of the axillary
      artery and the subclavian artery to the origin of the vertebral artery were
      measured in 14 human corpses by a flexible ruler. We calculated the hemodynamics
      within the vertebral artery, depending on different positions of the cannula tip,
      in a computer-calculated model. RESULTS: The mean distance from the axillary
      artery to the vertebral artery was 8.5 cm, and the mean distance from the
      subclavian artery to the vertebral artery was 6.7 cm. Computed flow calculations
      demonstrated reversed flow in the vertebral artery when the cannula tip was
      positioned too close to its orifice. To ensure safe supra-aortic flow, a cannula
      can be inserted securely up to 6.0 cm into the axillary artery and 4.2 cm into
      the subclavian artery. CONCLUSIONS: Direct cannulation of the right axillary
      artery can lead to cerebral malperfusion, caused by an obstruction of the
      vertebral artery's orifice by the arterial cannula or a subclavian steal
      phenomenon due to flow reversal. The safety of direct axillary artery cannulation
      can be improved by a well-considered dissecting site and insertion length of the
      cannula.

PMID- 23870326
TI  - Robotic harvest of intercostal muscle flap.

PMID- 23870327
TI  - Appraisal of the Karnofsky Performance Status and proposal of a simple
      algorithmic system for its evaluation.
AB  - BACKGROUND: For over 60 years, the Karnofsky Performance Status (KPS) has proven
      itself a valuable tool with which to perform measurement of and comparison
      between the functional statuses of individual patients. In recent decades
      conditions for patients have changed, and so too has the KPS undergone several
      adjustments since its initial development. DISCUSSION: The most important works
      regarding the KPS tend to focus upon a variety of issues, including but not
      limited to reliability, validity and health-related quality of life. Also
      discussed is the question of what quantity the KPS may in fact be said to
      measure. The KPS is increasingly used as a prognostic factor in patient
      assessment. Thus, questions regarding if and how it affects survival are
      relevant. SUMMARY: This review honors the original intention of the discoverer
      and gives an overview of adaptations made in recent years. The proposed algorithm
      suggests specific updates with the goal of ensuring continued adequacy and
      expediency in the determination of the KPS.

PMID- 23870329
TI  - Prevention of losses for hog farmers in China: insurance, on-farm biosecurity
      practices, and vaccination.
AB  - Using agricultural household survey data and claim records from insurers in
      China, this paper analyzes hog producers' choice of the ways to prevent possible
      losses and identifies the relationships among biosecurity practices, vaccination,
      and hog insurance. By combining one probit and two structural equations, we adopt
      three-stage estimations by a mixed-process model to obtain results. The findings
      indicate that biosecurity practices provide the basic infrastructure for
      operating pig farms and complement both the usage of quality vaccines and the
      uptake of hog insurance. In addition, there is a strong substitution relationship
      between the quality of vaccine and the demand for hog insurance. Hog farmers that
      implement better biosecurity practices are more likely to seek high-quality
      vaccines or buy into hog insurance schemes, but not both. For those households
      with hog insurance, better biosecurity status, better management practices, and
      higher-quality vaccines significantly help to reduce loss ratios. However, we
      also find a moral hazard effect in that higher premium expenditures by the
      insured households might induce larger loss ratios. 

PMID- 23870328
TI  - Effects of robotic guidance on the coordination of locomotion.
AB  - BACKGROUND: Functional integration of motor activity patterns enables the
      production of coordinated movements, such as walking. The activation of muscles
      by weightened summation of activation signals has been demonstrated to represent
      the spatiotemporal components that determine motor behavior during walking.
      Exoskeleton robotic devices are now often used in the rehabilitation practice to
      assist physical therapy of individuals with neurological disorders. These devices
      are used to promote motor recovery by providing guidance force to the patients.
      The guidance should in principle lead to a muscle coordination similar to
      physiological human walking. However, the influence of robotic devices on
      locomotor patterns needs still to be characterized. The aim of this study was to
      analyze the effect of force guidance and gait speed on the modular organization
      of walking in a group of eight healthy subjects. METHOD: A group of healthy
      subjects walked on a treadmill with and without robotic aiding at speeds of 1.5,
      2.0 and 2.5 Km/h. The guidance force was varied between 20%, 40%, 70% and 100%
      level of assistance. EMG recordings were obtained from seven leg muscles of the
      dominant leg and kinematic and kinetic features of the knee and hip joints were
      extracted. RESULTS: Four motor modules were sufficient to represent the variety
      of behavioral goals demanded during robotic guidance, with similar relationships
      between muscle patterns and biomechanical parameters across subjects, confirming
      that the low-dimensional and impulsive control of human walking is maintained
      using robotic force guidance. The conditions of guidance force and speed that
      maintained correct and incorrect (not natural) modular control were identified.
      CONCLUSION: In neurologically intact subjects robotic-guided walking at various
      force guidance and speed levels does not alter the basic locomotor control and
      timing. This allows the design of robotic-aided rehabilitation strategies aimed
      at the modulation of motor modules, which are altered in stroke.

PMID- 23870330
TI  - Video-assisted thoracoscopic surgery versus robotic-assisted thoracoscopic
      surgery in the surgical treatment of Masaoka stage I thymoma.
AB  - BACKGROUND: The purpose of this study was to compare perioperative outcomes in
      patients who underwent video-assisted thoracoscopic surgery or robot-assisted
      thoracoscopic surgery and assess the feasibility of robotic-assisted thymectomy
      for the treatment of Masaoka stage I. METHODS: We evaluated the short-term
      outcomes of 46 patients who underwent surgery for Masaoka stage I thymoma without
      myasthenia gravis between January 2009 and June 2012. Of these patients, 25
      received unilateral video-assisted thoracoscopic surgery (VATS group) and the
      rest 21 recieved unilateral robotic-assisted thoracoscopic surgery (RATS group).
      We evaluated the duration of surgery, amount of intraoperative blood loss,
      duration of chest drainage, duration of postoperative hospital stay,
      hospitalization costs, postoperative complications and oncological outcomes.
      RESULTS: The duration of surgery was not significantly different between the two
      groups. Intraoperative blood loss volumes did not differ significantly between
      the VATS and RATS groups (86.8 mL and 58.6 mL, respectively; P=0.168). The
      postoperative hospital stay was significantly shorter in the RATS group (3.7 days
      vs. 6.7 days; P <0.01), and the postoperative pleural drainage volume of the RATS
      group was significantly less than VATS group (1.1 days vs. 3.6 days; P <0.01). No
      patients in the RATS group needed conversion to open surgery. However, in the
      VATS series, one patient had conversion to an open procedure. No surgical
      complications were observed except that one case had pulmonary atelectasis in the
      RATS group and one case developed pneumonia after surgery. Use of robot is much
      more expensive than video. No early recurrence was observed in both groups.
      CONCLUSIONS: Robotic thymectomy is feasible and safe for Masaoka stage I thymoma.
      RATS is equally minimally invasive as VATS and results in a shorter drainage
      period and reduced hospital stay compared with the VATS approach.

PMID- 23870331
TI  - Prevalence of delirium among outpatients with dementia.
AB  - BACKGROUND: Delirium and dementia are highly interrelated. However, few
      comprehensive epidemiological studies have examined this altered state of
      consciousness superimposed on dementia. We investigated the frequency of delirium
      in patients with dementia, its prevalence in patients with each dementia type,
      and its association with cerebrovascular disease (CVD) in patients with
      neurodegenerative dementias. METHODS: We studied 261 consecutive outpatients in
      the memory clinic of a psychiatric hospital between April 2010 and September
      2011. All patients underwent routine laboratory tests and computed tomography
      (CT), and their Mini-Mental State Examination, Neuropsychiatric Inventory (NPI),
      Physical Self-Maintenance Scale (PSMS), and Delirium Rating Scale - Revised 98
      scores were recorded. The diagnosis of delirium was based on the Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition, text revision. CVD was
      detected by CT. RESULTS: Among the 206 patients with dementia, delirium was
      present in 40 (19.4%). The proportion of patients who experienced episodes of
      delirium was 14.7% in the Alzheimer's disease, 34.4% in the vascular dementia,
      31.8% in the dementia with Lewy bodies, and none in frontotemporal lobar
      degeneration. Delirium was frequently observed in patients with dementia and CVD.
      The NPI total and agitation subscale scores were significantly higher in dementia
      patients with delirium than in those without delirium. PSMS scores were
      significantly lower for patients with delirium than for patients without
      delirium. CONCLUSIONS: The frequency of delirium varies with each dementia type.
      In addition, delirium decreases activities of daily living, exaggerates
      behavioral and psychological symptoms dementia, and is associated with CVD in
      patients with neurodegenerative dementias.

PMID- 23870333
TI  - Clinical applications for magnetic resonance guided high intensity focused
      ultrasound (MRgHIFU): present and future.
AB  - It has been well known for decades that high intensity focused ultrasound (HIFU)
      generates heat in tissues resulting in coagulative necrosis. Implementation,
      however, has been slow, due to difficulties with finding an appropriate imaging
      modality that could not only guide treatment, but also provide real-time thermal
      feedback. These problems have been overcome with the newest magnetic resonance
      guided high intensity focused ultrasound systems (MRgHIFU). With its superior
      spatial resolution enabling accurate image guidance coupled with its ability to
      provide real-time thermography during treatments, MRI is moving further into the
      realm of therapeutics for oncologic patient care. This article will discuss the
      implementation of an MR-guided HIFU system, current clinical indications and
      touch on future directions. 

PMID- 23870332
TI  - Follicle stimulating hormone modulates ovarian stem cells through alternately
      spliced receptor variant FSH-R3.
AB  - BACKGROUND: We have earlier reported that follicle stimulating hormone (FSH)
      modulates ovarian stem cells which include pluripotent, very small embryonic-like
      stem cells (VSELs) and their immediate descendants 'progenitors' termed ovarian
      germ stem cells (OGSCs), lodged in adult mammalian ovarian surface epithelium
      (OSE). FSH may exert pleiotropic actions through its alternatively spliced
      receptor isoforms. Four isoforms of FSH receptors (FSHR) are reported in
      literature of which FSH-R1 and FSH-R3 have biological activity. Present study was
      undertaken to identify FSHR isoforms mediating FSH action on ovarian stem cells,
      using sheep OSE cells culture as the study model. METHODS: Cultures of sheep OSE
      cells (a mix of epithelial cells, VSELs, OGSCs and few contaminating red blood
      cells) were established with and without FSH 5IU/ml treatment. Effect of FSH
      treatment on self-renewal of VSELs and their differentiation into OGSCs was
      studied after 15 hrs by qRT-PCR using markers specific for VSELs (Oct-4A, Sox-2)
      and OGSCs (Oct-4). FSH receptors and its specific transcripts (R1 and R3) were
      studied after 3 and 15 hrs of FSH treatment by immunolocalization, in situ
      hybridization and qRT-PCR. FSHR and OCT-4 were also immuno-localized on sheep
      ovarian sections, in vitro matured follicles and early embryos. RESULTS: FSH
      treatment resulted in increased stem cells self-renewal and clonal expansion
      evident by the appearance of stem cell clusters. FSH receptors were expressed on
      ovarian stem cells whereas the epithelial cells were distinctly negative. An
      increase in R3 mRNA transcripts was noted after 3 hrs of FSH treatment and was
      reduced to basal levels by 15 hrs, whereas R1 transcript expression remained
      unaffected. Both FSHR and OCT-4 were immuno-localized in nuclei of stem cells,
      showed nuclear or ooplasmic localization in oocytes of primordial follicles and
      in cytoplasm of granulosa cells in growing follicles. CONCLUSIONS: FSH modulates
      ovarian stem cells via FSH-R3 to undergo potential self-renewal, clonal expansion
      as 'cysts' and differentiation into oocytes. OCT-4 and FSHR proteins (required
      initially to maintain pluripotent state of VSELs and for FSH action respectively)
      gradually shift from nuclei to cytoplasm of developing oocytes and are later
      possibly removed by surrounding granulosa cells as the oocyte prepares itself for
      fertilization.

PMID- 23870334
TI  - Five-year analysis of magnetic resonance imaging as a screening tool in women at
      hereditary risk of breast cancer.
AB  - INTRODUCTION: Women at very high risk of breast cancer are recommended to
      undertake enhanced surveillance with annual MRI in addition to mammography. We
      aimed to review the performance of breast MRI as a screening modality over its
      first 5 years at our institution. METHODS: The study used a retrospective review
      using prospectively collected data from a consecutive series of women at high
      risk of developing breast cancer undergoing surveillance MRI. RESULTS: Two
      hundred twenty-three women had at least one screening MRI. The median age was 42
      years old. Sixty-nine (30.9%) were confirmed genetic mutation carriers. The
      remaining 154 (69.1%) women were classified as high risk based on family history,
      without a confirmed genetic mutation. Three hundred forty screening MRI studies
      were performed. Of these, 69 patients (20.3%) were recalled for further
      assessment. There was a significant reduction in the recall rate throughout the
      study for prevalent screens, from 50% (17/34) in 2008 to 14% (9/54) in 2011 (P =
      0.004). The overall biopsy rate was 39 in 340 screens (11.5%). Four cancers were
      identified. Three were in confirmed BRCA1/BRCA2 mutation carriers, and one was
      found to be a carrier after the cancer was diagnosed. All four were identified as
      suspicious on MRI, with two having normal mammography. The cancer detection rate
      of MRI was 1.2% (4/340 screens). The overall positive predictive value was 7.0%,
      6.7% for prevalent screens and 7.1% for subsequent screens. CONCLUSIONS: Breast
      MRI as a screening modality for malignant lesions in women with high hereditary
      risk is valuable. The recall rate, especially in the prevalent round, improved
      with radiologist experience.

PMID- 23870335
TI  - Estimated radiation dose and image quality comparison of the scan protocols in
      dual-source computed tomography coronary angiography.
AB  - INTRODUCTION: Radiation exposure from computed tomography coronary angiography
      (CTCA) is of particular concern and several techniques have been introduced to
      lower the radiation dose. In this study, we aimed to compare the diagnostic image
      quality and estimated radiation dose of the three CTCA acquisition protocols in a
      recently introduced second generation dual-source computed tomography. METHODS:
      Two hundred consecutive subjects underwent dual-source CTCA by using high-pitch
      spiral, sequential and retrospective spiral protocols. Effective radiation dose,
      expressed in millisieverts, was calculated as the product of the dose-length
      product times a conversion factor of 0.014. Image quality was evaluated on a per
      segment basis, with a four-point scale. RESULTS: For the high-pitch spiral,
      sequential and retrospective spiral protocols, mean effective radiation doses
      were 1.41 +/- 0.56, 5.50 +/- 2.06 and 7.79 +/- 2.25 mSv and mean per-subject
      image scores were 2.8 +/- 0.7, 2.2 +/- 0.8 and 2.5 +/- 0.8, respectively.
      Radiation dose of the high-pitch mode was significantly lower (P < 0.001) than
      the sequential and retrospective spiral modes, and statistical analysis for image
      quality revealed a significant difference between the high-pitch spiral and the
      sequential modes (P < 0.05). CONCLUSION: Dual-source CTCA using high-pitch
      acquisition considerably lowers radiation exposure in subjects with a low and
      stable heart rate and maintains good image quality, especially when the subjects
      have a body mass index <=25 and a tube voltage of 80 or 100 kV is used. However,
      when sequential and retrospective spiral modes are used in the same device, mean
      radiation doses can increase roughly three and five times more, respectively.

PMID- 23870336
TI  - Efficacy of 'breath holding at ease' during CT pulmonary angiography in the
      improvement of contrast enhancement in pulmonary arteries.
AB  - INTRODUCTION: The aim of this study is to assess whether breath-hold at ease by
      patients during the CT pulmonary angiography (CTPA) will improve contrast
      enhancement in pulmonary arteries. METHODS: Retrospective review was conducted on
      51 consecutive CTPA studies undertaken in the traditional method of patients
      taking deep inspiration and breath-hold immediately prior to scanning, and
      subsequently 75 consecutive CTPA studies with patients breathing-holding at ease
      immediately prior to and during the scanning. Attenuation values in pulmonary
      arteries of different anatomical levels in both groups were measured in
      Hounsfield unit (HU). Results were compared between the two groups. RESULTS: The
      mean attenuation value in pulmonary arteries including pulmonary trunk, main and
      proximal pulmonary arteries calculated in HU in the 'deep inspiration and breath
      hold' group was 327 HU (95% confidence interval: 315 to 339 HU). The mean
      attenuation value in pulmonary arteries in the 'breath hold at ease' group was
      calculated to be 390 HU (95% confidence interval: 381 to 399 HU); that is, an
      overall 17.95% increase (P-value < 0.0001) in attenuation value in this group.
      CONCLUSIONS: By asking patients to breath-hold at ease instead of taking deep
      inspiration and breath hold prior to CTPA scan can effectively improve contrast
      enhancement in pulmonary arteries, therefore producing a higher-quality CT
      pulmonary angiography scan.

PMID- 23870337
TI  - Cost analysis of intracranial aneurysmal repair by endovascular coiling versus
      flow diversion: at what size should we use which method?
AB  - INTRODUCTION: Flow diverters enable intracranial aneurysmal repair without the
      need to enter the aneurysm sac. Concerns, however, have been raised regarding the
      cost compared with coiling techniques. The aim of this study was to evaluate the
      relative costs for different aneurysm sizes to ascertain if different sizes are
      more cost-effectively treated by a particular method. METHODS: Patients
      undergoing aneurysmal repair at two neurovascular referral centres between
      September 2005 and August 2010 were included; patients who underwent coiling for
      recurrences of prior microneurosurgical clipping were excluded. These aneurysms
      were stratified into three size groups. The average and median number of coils or
      flow diverters and the average and median costs of treatment of each size
      category were calculated. RESULTS: Four hundred twenty-nine aneurysms were
      treated. Of these, 409 were coiled with or without assist devices. Forty-eight
      percent fell under Group A (<7 mm), 36% under Group B (7-12 mm) and 16% under
      Group C (>12 mm). Twenty aneurysms were flow diverted. Of these, 14 were treated
      de novo, five previously coiled and one previously clipped. Twenty percent
      belonged in Group A, 25% in Group B and 55% in Group C. The highest procedural
      costs in the coiling group were Group C aneurysms requiring stent assistance,
      with an average of $24 563 (median $23 860). Using flow diversion, the average
      was $24 650 (median $16 490). CONCLUSION: Given the price parity threshold
      crossed for aneurysms >12 mm requiring stent assistance and the relative ease of
      the flow diverter technique, we suggest that flow diversion should be considered
      the first-line treatment for aneurysms in this category.

PMID- 23870338
TI  - Ultrashort time-to-echo MRI of the cartilaginous endplate: technique and
      association with intervertebral disc degeneration.
AB  - INTRODUCTION: The purpose of this study was to report the feasibility of the
      ultrashort time-to-echo (UTE) MRI technique to assess cartilaginous endplate
      (CEP) defects in humans in vivo and to assess their relationship with
      intervertebral disc (IVD) degeneration. METHODS: Nine volunteer subjects (mean
      age = 43.9 years; range = 22-61 years) were recruited, representing 54 IVDs and
      108 CEPs. The subjects underwent T2-weighted and UTE MRI to assess for the
      presence and severity of IVD degeneration, and for the presence of CEP defects,
      respectively, from T12 to S1. IVD degeneration was graded according to the
      Schneiderman et al. classification on T2-weighted MRI. CEP defects were defined
      on UTE MRI as discontinuity of high signal over four consecutive images and were
      independently assessed by two observers. RESULTS: Thirty-seven out of 108 (34.3%)
      CEPs had defects, which mainly occurred at T12/L1, L1/L2 and L4/L5 (P = 0.008).
      Multivariate logistic regression revealed that lower body mass index (P = 0.009)
      and younger (P = 0.034) individuals had a decreased likelihood of having CEP
      defects. A statistically significant association was found to exist between the
      presence of CEP defects and IVD degeneration (P = 0.036). A higher prevalence of
      degenerated IVDs with CEP defects was found at L4/5 and L5/S1, while degenerated
      IVDs with no CEP defects were found throughout the whole lumbar region. Mean IVD
      degeneration scores of the L4/5 and L5/S1 levels with CEP defects were higher in
      comparison with those with no CEP defects. CONCLUSIONS: Our study demonstrates
      the feasibility of using UTE MRI in humans in vivo to assess the integrity of the
      CEP. A statistically significant association was found to exist between the
      presence of CEP defects and IVD degeneration. In the lower lumbar region, more
      severe degeneration was found to occur in the IVDs with CEP defects than in those
      without defects.

PMID- 23870339
TI  - Examining the sensitivity of ultrasound-guided large core biopsy for invasive
      breast carcinoma in a population screening programme.
AB  - INTRODUCTION: To evaluate the sensitivity of ultrasound-guided core-needle biopsy
      (UCB) in invasive breast carcinoma and to establish causes of false-negative
      biopsy in a population screening programme. METHOD: We identified 571 consecutive
      women diagnosed with surgically proven invasive breast cancer. Histology from 14
      gauge UCB was compared with surgical histology to identify true-positive and
      false-negative ultrasound core biopsies. True-positive and false-negative groups
      were compared for tumour size and histology. On blinded review of UCB images and
      pathology reports from false negative (n = 20) and a random sample of true
      positive cases (n = 80), we compared core sample number and needle visualisation
      in the lesion. RESULTS: Of 571 carcinomas sampled with UCB, 551 (96.5%) were true
      positive and 20 (3.5%) were false negative. The mean core number was 2.0 (range 1
      3) for false negatives and 2.25 (range 1-4) for true positives (P = 0.27). Mean
      tumour sizes were 13.3 and 16.2 mm for the false-negative and true-positive
      groups, respectively (P = 0.25). Tubular carcinomas represented 30% (6/20) of
      false-negative cases compared with 5.1% (28/551) of the true-positive cases (P <
      0.001). On blinded review, needle visualisation within the lesion was
      demonstrated in 47.4% (9/19) of false-negative cases and 76.3% (61/80) of true
      positive cases (P = 0.02). CONCLUSION: We demonstrated a sensitivity of 96.5%
      with a mean of 2.21 cores. False-negative results were more likely in the absence
      of post-fire needle position verification and with tubular carcinomas. Neither
      tumour size nor core number predicted diagnostic accuracy.

PMID- 23870340
TI  - Sinus valsalva aneurysm on cardiac CT angiography: assessment and detection.
AB  - After the advent of ECG gated cardiac CT angiography (CCTA) there has been
      significant improvement in image quality of the ascending aorta. As a result the
      sinuses of valsalva are readily assessable. Sinuses of valsalva aneurysm can
      cause significant dysfunction of the aortic root and annulus and can be
      congenital or acquired. The aneurysm most commonly originates from the right
      coronary sinus. Complications related to sinuses of valsalva aneurysm can cause
      chest pain and can be life threatening. The cardiac imager should actively assess
      the sinuses of valsalva in every CCTA study. 

PMID- 23870341
TI  - Computed tomography of the temporomandibular joint.
AB  - We present a pictorial review of the spectrum of temporomandibular joint (TMJ)
      pathology diagnosed with CT. Although MRI is the modality of choice for most TMJ
      pathology, CT is useful when MRI is contraindicated or not accessible. With
      attention to technique and viewing conditions, CT is capable of showing internal
      disc derangement, arthritis, neoplasms and non-TMJ regional pathology at a
      relatively low radiation dose. 

PMID- 23870342
TI  - Use of flat panel DynaCT myelography to locate the site of CSF leak.
AB  - Spontaneous intracranial hypotension is often treated conservatively or with
      epidural blood patch. Patients who are resistant to these treatments require
      accurate imaging localisation of the site of cerebrospinal fluid (CSF) leak for
      surgical repair. We describe two patients where MRI, CT myelography and MRI
      gadolinium myelography showed evidence of a large volume of epidural CSF, but
      failed to identify the pressure site of leak. Subsequently, DynaCT (Siemens,
      Erlangen, Germany) accurately identified the site with confidence in both cases,
      confirmed at surgery. This technique of using a flat panel detector-based,
      angiographic system to produce high quality, high-contrast multiplanar CT images
      for detecting the source of rapid CSF leak is detailed. 

PMID- 23870343
TI  - Lymphangiography as therapeutic management of chylothorax.
AB  - Chylothorax is a rare post surgical complication. It is often initially treated
      using conservative management such as chest drain insertion, a medium chain
      triglyceride diet, total parenteral nutrition and somatostatin analogues.
      Lymphangiography has been used in the past, mainly to identify the site of a
      chyle leak, but there have been reports where lymphangiography has been
      therapeutic in the management of chylothorax and has led to resolution of the
      chyle leak. This paper describes the case of a 15-year-old male who presented
      with a post-operative chylothorax. He was initially managed conservatively, which
      failed to stop the chyle leak and lymphangiography was performed. Imaging
      confirmed that lymphangiography was successful in stopping the chyle leak,
      leading to resolution of the chylothorax. CONCLUSION: This case demonstrates that
      lymphangiography can be used as a therapeutic measure in the management of a
      chylothorax.

PMID- 23870344
TI  - Extramedullary haematopoiesis simulating osseous neoplasia.

PMID- 23870345
TI  - Chest radiographic appearances in swine flu.

PMID- 23870346
TI  - The written radiological report guidelines.

PMID- 23870347
TI  - High-powered percutaneous microwave ablation of stage I medically inoperable non
      small cell lung cancer: a preliminary study.
AB  - PURPOSE: To retrospectively evaluate the feasibility and outcome of using high
      powered percutaneous microwave ablation (MWA) in treating medically inoperable
      early stage non-small cell lung cancer. MATERIALS AND METHODS: From November 2010
      to June 2012, 15 patients underwent CT-guided MWA of 15 tumours in 16 sessions.
      One patient had a second ablation session for local tumour progression. Each
      tumour had a diameter of 40 mm or less (median 24 mm). Treatment outcome was
      evaluated using modified response evaluation criteria in solid tumours criteria
      based on follow-up contrast-enhanced CT studies and 18-F fluorodeoxyglucose
      positron emission tomography scans. RESULTS: Thirty-three ablation cycles of 15
      tumours were performed in 16 sessions (2.1 per session), with a median duration
      of 2.5 min per ablation. Treatment was completed in all cases with no 30-day
      mortality. At a median follow-up period of 1 year, local progression was
      identified following 5/16 (31%) ablation sessions. Eleven out of 16 (69%) of MWAs
      had shown local treatment response, with 9/11 displaying complete response and
      2/11 displaying partial response. Local progression on follow up was
      predominantly seen in pleural-based tumours that were greater than 30 mm in
      longest axial diameter (4/5 cases). The main adverse event was a pneumothorax,
      which occurred in 10/16 (63%) of procedures, but a chest tube was only required
      in 2/16 (13%) cases. CONCLUSION: Percutaneous MWA in early stage non-small cell
      lung cancer is well tolerated and has promising midterm outcomes.

PMID- 23870348
TI  - Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small
      cell lung cancer treated with definitive chemoradiotherapy.
AB  - INTRODUCTION: For many cancers, tumour hypoxia is an adverse prognostic factor,
      and increases chemoradiation resistance; its importance in non-small cell lung
      cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using
      fluoroazomycin arabinoside ((18) F-FAZA) positron emission tomography (PET) scans
      among patients with locoregionally advanced NSCLC treated with definitive
      chemoradiation. METHODS: Patients with stage IIIA-IIIB NSCLC underwent (18) F
      FAZA PET scans and (18) F-2-deoxyglucose (FDG)-PET scans within 4 weeks of
      commencing and 8 weeks following conventionally-fractionated concurrent platinum
      based chemoradiation (60 Gy). Intra-lesional hypoxic volumes of the primary and
      nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural
      hypoxia was correlated with disease free survival (DFS). RESULTS: Seventeen
      patients underwent pre-treatment (18) F-FAZA PET and FDG-PET scans. Intra
      lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic
      volumes were consistently smaller than FDG-PET volumes (P = 0.012). There was no
      statistical difference between the mean FDG-PET volumes in patients with or
      without baseline hypoxia (P = 0.38). Eight patients with baseline hypoxia had
      post treatment (18) F-FAZA scans and 6 of these (75%) had resolution of imageable
      hypoxia following chemoradiation. The DFS was not significantly different between
      the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P
      = 0.42). CONCLUSIONS: Intra-lesional hypoxia, as detected by (18) F-FAZA PET, was
      present in 65% of patients with locally-advanced NSCLC and resolved in the
      majority of patients following chemoradiation. Larger studies are required to
      evaluate the prognostic significance of the presence and resolution of hypoxia
      assessed by PET in NSCLC.

PMID- 23870349
TI  - Implementation of an image guided intensity-modulated protocol for post
      prostatectomy radiotherapy: planning data and acute toxicity outcomes.
AB  - INTRODUCTION: There is substantial interest in implementation of image-guided
      intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We
      describe our implementation of IG-IMRT, and examine how often published organ-at
      risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute
      genitourinary and gastrointestinal toxicities when patients were treated
      according to our protocol. METHODS: Patients were eligible if they received post
      prostatectomy radiotherapy (PPRT). Planning data were collected prospectively,
      and toxicity assessments were collected before, during and after treatment.
      RESULTS: Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy
      (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of
      V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients,
      respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy <
      17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint
      (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new
      grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3
      gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review.
      Overall deterioration in urinary and gastrointestinal symptoms occurred in 33
      (44%) and 35 (47%) of patients respectively. CONCLUSIONS: We report on our
      implementation of PPRT which takes into account nationally adopted guidelines,
      with a margin reduction supported by use of daily image guidance. Non-IMRT OAR
      constraints were met in most cases. IMRT-specific constraints were less often
      achieved despite margin reductions, suggesting the need for review of guidelines.
      Severe toxicity was rare, and most patients did not experience deterioration in
      urinary or bowel function attributable to radiotherapy.

PMID- 23870350
TI  - Australasian brachytherapy audit: results of the 'end-to-end' dosimetry pilot
      study.
AB  - INTRODUCTION: We present the results of a pilot study to test the feasibility of
      a brachytherapy dosimetry audit. METHODS: The feasibility study was conducted at
      seven sites from four Australian states in both public and private centres. A
      purpose-built cylindrical water phantom was imaged using the local imaging
      protocol and a treatment plan was generated to deliver 1 Gy to the central (1 of
      3) thermoluminescent dosimeter (TLD) from six dwell positions. RESULTS: All
      centres completed the audit, consisting of three consecutive irradiations, within
      a 2-h time period, with the exception of one centre that uses a pulsed dose rate
      brachytherapy unit. All TLD results were within 4.5% of the predicted value, with
      the exception of one subset where the dwell position step size was incorrectly
      applied. CONCLUSIONS: While the limited data collected in the study demonstrated
      considerable heterogeneity in clinical practice, the study proved a brachytherapy
      dosimetry audit to be feasible. Future studies should include verification of
      source strength using a Standard Dosimetry Laboratory calibrated chamber, a
      phantom that more closely mimics the clinical situation, a more comprehensive
      review of safety and quality assurance (QA) procedures including source dwell
      time and position accuracy, and a review of patient treatment QA procedures such
      as applicator position verification.

PMID- 23870351
TI  - Accrual to Trans-Tasman Radiation Oncology Group-sponsored trials 2010-2012.
AB  - INTRODUCTION: Few trials groups report analyses of accrual. Although Trans-Tasman
      Radiation Oncology Group (TROG) has reported accrual within individual trials, no
      analysis has ever been reported. Type A trials are those trials for which TROG is
      the principal sponsor and are dependent on accrual from TROG centres. The aim of
      this study was to review accrual rates to type A trials over the last 3 years.
      METHODS: All type A trials that had presented accrual data during the TROG annual
      scientific meetings and the trials review meetings between April 2010 and April
      2012 were reviewed. Expected accrual rate (EAR) and actual accrual rate (AAR)
      were estimated from accrual curves as well as initial delays in accrual. Ratios
      of AAR to EAR (RAEAR) were calculated. RESULTS: There were 16 type A trials from
      which estimates could be made. The median EAR was 40 patients per year and the
      median AAR was 20 patients per year. Wide variations in each were noted and the
      median RAEAR was 0.67. The median initial delay was 7.5 months. CONCLUSIONS:
      Although TROG is a highly successful trials organisation, the median AAR is only
      half of the median EAR and in only three trials (19%) was the AAR the same or
      more than the EAR. Future reports could address potential factors affecting the
      AAR but would require prospective data collection. The RAEAR is one of many
      factors that can be used to help determine which trials should continue. Overall
      rates of accrual can be used as a record of TROG's productivity.

PMID- 23870352
TI  - Impact of the spinal cord position uncertainty on the dose received during head
      and neck helical tomotherapy.
AB  - INTRODUCTION: The study aims to establish the optimal planning risk volume (PRV)
      to the spinal cord (SC) for oropharyngeal cancer patients during adaptive
      radiation therapy with concurrent chemotherapy. METHODS: Geometrical
      uncertainties of the SC were evaluated. Differences between planned and delivered
      maximum doses to each part of the SC were established for every fraction dose and
      for cumulative dose. Maximum doses were evaluated as a dose received in 0.5 and 1
      cm(3) of the analysed part of the SC defined as C1-C2, C3-C4, C5-C6 and C7-Th1
      where Cn was a n-th cervical vertebra (n = 1, ... , 7) and Th1 was the first
      thoracic vertebra. Finally, relations between dose differences and geometrical
      uncertainties were analysed using a relative risk (RR) and the importance of the
      PRV dose gradient to establish an optimal PRV for the SC. RESULTS: Prospective
      study based on the 875 observations from 25 oropharyngeal cancer patients was
      performed. The C1-C2 part of the SC is most exposed to risk of overdosage during
      chemoradiation for patients with oropharyngeal cancer due to its proximity to the
      clinical target volume (CTV). Doses received by other parts of the SC are
      smaller, with the lowest dose delivered to C7-Th1. For the C1-C2, delivered dose
      was higher than planned dose by 11%, while for the C7-Th1, this difference was
      smaller than 7%. The lowest movement of individual parts of the SC were detected
      for the C1-C2 and the highest for the C7-Th1. The standard deviations of the mean
      shift ranged respectively from 0.9 to 1.4 mm and from 1.3 to 2.9 mm. For each
      part of the SC delivered dose was smaller than planned dose to the PRV (RR < 1).
      CONCLUSION: Our study showed that for chemoradiation of oropharyngeal cancer,
      using daily image guidance and proper plan adaptation scheme, the current PRV
      margin for the SC could be reduced to 4 mm.

PMID- 23870353
TI  - Once-daily reirradiation for rectal cancer in patients who have received previous
      pelvic radiotherapy.
AB  - INTRODUCTION: The purpose of this study is to assess the efficacy and toxicity
      using once-daily reirradiation for patients with rectal cancer having received
      previous pelvic radiotherapy. METHOD: Between June 1997 and June 2008, 56
      patients were identified having received previous pelvic radiotherapy and
      received reirradiation for rectal cancer. Reirradiation intent was palliative in
      43 patients, and preoperative/postoperative in 13 patients. Eighty per cent of
      patients received concurrent chemotherapy (n = 45). RESULTS: The median dose
      fractionation reirradiation schedule was 39.6 Gy in 22 fractions once daily
      (range 20-39.6 Gy), and the median cumulative radiation dose was 87.3 Gy. Seven
      patients experienced a grade 3 acute toxicity, with no grade 4 event. Fifty-one
      patients (91%) completed the treatment and five patients required a treatment
      break. The overall symptomatic response rate was 88% at three months post
      reirradiation. There was one late effect of skin ulceration among patients
      reirradiated palliatively. Median overall survival was 39 months in patients
      undergoing radical surgery versus 15 months in patients reirradiated palliatively
      (P < 0.001). CONCLUSION: Once-daily reirradiation to a total dose of <=39.6 Gy is
      relatively safe in the treatment of patients with rectal cancer after previous
      pelvic radiotherapy. It is effective in symptom control and provides an
      additional option in management of local recurrence.

PMID- 23870354
TI  - Interobserver variability of radiation therapists aligning to fiducial markers
      for prostate radiation therapy.
AB  - INTRODUCTION: As the use of fiducial markers (FMs) for the localisation of the
      prostate during external beam radiation therapy (EBRT) has become part of routine
      practice, radiation therapists (RTs) have become increasingly responsible for
      online image interpretation. The aim of this investigation was to quantify the
      limits of agreement (LoA) between RTs when localising to FMs with orthogonal
      kilovoltage (kV) imaging. METHODS: Six patients receiving prostate EBRT utilising
      FMs were included in this study. Treatment localisation was performed using kV
      imaging prior to each fraction. Online stereoscopic assessment of FMs, performed
      by the treating RTs, was compared with the offline assessment by three RTs.
      Observer agreement was determined by pairwise Bland-Altman analysis. RESULTS:
      Stereoscopic analysis of 225 image pairs was performed online at the time of
      treatment, and offline by three RT observers. Eighteen pairwise Bland-Altman
      analyses were completed to assess the level of agreement between observers.
      Localisation by RTs was found to be within clinically acceptable 95% LoAs.
      CONCLUSIONS: Small differences between RTs, in both the online and offline
      setting, were found to be within clinically acceptable limits. RTs were able to
      make consistent and reliable judgements when matching FMs on planar kV imaging.

PMID- 23870356
TI  - From coordination chemistry to biological chemistry of aluminium.
AB  - The paper gives a review on the importance of distribution of Al in biological
      fluids, primarily in the lights of the works of the author in Al chemistry. It
      starts with studies of interactions of Al(III) with small biomolecules, such as
      aliphatic and aromatic hydroxycarboxylic acids, and inorganic and organic
      phosphates. A significant part of this review deals with the problems of
      description of the biospeciation of Al(III) in serum, where besides the
      thermodynamic conditions the role of time is also considered in the case of this
      sluggish metal ion. The Al(III) complexes of the other large group of
      biomolecules, proteins and their building blocks (oligo)peptides and amino acids
      are also discussed, where the role of the type of the side chain donors and the
      extent of preorganisation are considered in the efficiency of metal ion binding.
      The application of low molecular mass chelator molecules in restoring the
      dysfunctioning metal ion (including Al(III)) homeostasis in the treatment of
      Alzheimer's disease is also discussed in the paper.

PMID- 23870357
TI  - The medicare glaucoma screening benefit: a critical program that misses its
      target.

PMID- 23870358
TI  - Regular aspirin use and risk of age-related macular degeneration.

PMID- 23870359
TI  - Refractive error after cataract surgery combined with descemet stripping
      automated endothelial keratoplasty.
AB  - PURPOSE: To assess refractive error after cataract surgery combined with Descemet
      stripping automated endothelial keratoplasty using adjusted keratometric (K)
      readings to calculate intraocular lens (IOL) power. DESIGN: Prospective,
      interventional case series. METHODS: One eye of 39 consecutive patients with
      Fuchs endothelial dystrophy and cataract were included. To calculate IOL power
      before surgery, the Javal steep and flat K readings (Haag-Streeit) were adjusted
      by reducing their value by -1.19 diopters (D); the axial length was measured by
      immersion biometry, and the standard A-constant was used. Surgery included
      phacoemulsification, IOL (Acrysof SN60AT; Alcon) implantation within the capsular
      bag, and Descemet stripping automated endothelial keratoplasty using posterior
      lamella prepared with a 300-MUm head microkeratome (Moria). The absolute
      prediction error (absolute difference between predicted and achieved refraction)
      was assessed 6 months after surgery. RESULTS: The mean power of the implanted IOL
      was 23.22 +/- 2.90 D. The mean predicted and achieved refractions were -0.27 +/-
      0.26 D and -0.23 +/- 0.73 D, respectively. The mean absolute prediction error was
      0.59 +/- 0.42 D (range, 0.05 to -1.52 D). The postoperative spherical equivalent
      fell within +/-0.50 D, +/-1.00 D, and +/-2.00 D of the predicted refraction in
      55.5%, 83.3%, and 100% of cases, respectively. Had the IOL power been calculated
      without adjusting the K readings, the mean absolute prediction error would have
      been significantly higher (0.86 +/- 0.62 D; P = .04). CONCLUSIONS: In this study,
      in which posterior lamellae were prepared using a 300-MUm head microkeratome,
      adjusting preoperative K readings by -1.19 D led to accurate IOL power
      calculation and highly predictable refractive error after cataract surgery
      combined with Descemet stripping automated endothelial keratoplasty.

PMID- 23870360
TI  - Initiation of anti-TNF therapy and the risk of optic neuritis: from the Safety
      Assessment of Biologic ThERapy (SABER) Study.

PMID- 23870361
TI  - Reply: To PMID 22967869.

PMID- 23870362
TI  - Change in efficiency of aspheric intraocular lenses based on pupil diameter.

PMID- 23870363
TI  - Reply: To PMID 23218695.

PMID- 23870364
TI  - Reply: To PMID 23218706.

PMID- 23870365
TI  - Impact of the revised American Academy of Ophthalmology guidelines regarding
      hydroxychloroquine screening on actual practice.

PMID- 23870366
TI  - Ocular torsion among patients with intermittent exotropia: relationships with
      disease severity factors.

PMID- 23870367
TI  - Reply: To PMID 23022165.

PMID- 23870368
TI  - Effect of timolol on refractive outcomes in eyes with myopic regression after
      laser in situ keratomileusis: a prospective randomized clinical trial.

PMID- 23870369
TI  - Reply: To PMID 22935601.

PMID- 23870372
TI  - Applying the Advancing Excellence in America's Nursing Homes Circle of Success to
      improving and sustaining quality.
AB  - Looking forward to the Quality Assurance Performance Improvement (QAPI) program
      to be implemented and required in 2014, and as nursing home staff provide care
      for residents with increasingly complex health issues, knowledge of how to
      implement quality improvement (QI) is imperative. The nursing home administrator
      and director of nursing (DON) provide overall leadership, but it is the primary
      responsibility of the DON and other registered nurse staff to implement and
      manage the day to day QI process. This article describes potential roles of
      nursing leaders and key components of a QI project using a pressure ulcer case
      study exemplar to illustrate a quality improvement process. The authors suggest
      specific methods that RN leaders can employ using the Advancing Excellence
      Campaign Circle of Success as an organizing framework along with evidence-based
      resources. Nursing home leaders could use this article as a guideline for
      implementing any clinical quality improvement process. 

PMID- 23870371
TI  - Brain natriuretic peptide is not predictive of dilated cardiomyopathy in Becker
      and Duchenne muscular dystrophy patients and carriers.
AB  - BACKGROUND: Cardiomyopathy is reported in Duchenne and Becker muscle dystrophy
      patients and female carriers. Brain Natriuretic peptide (BNP) is a hormone
      produced mainly by ventricular cardiomyocytes and its production is up regulated
      in reaction to increased wall stretching. N-terminal-proBNP (NT-proBNP) has been
      shown to be a robust laboratory parameter to diagnose and monitor cardiac
      failure, and it may be helpful to screen for asymptomatic left ventricular
      dysfunction. Therefore we tested whether NT-proBNP can distinguish patients with
      Duchenne or Becker muscular dystrophy patients and carriers of a dystrophin
      mutation with a dilated cardiomyopathy from those without. METHODS: In a cohort
      of Duchenne and Becker muscle dystrophy patients (n = 143) and carriers (n = 219)
      NT-proBNP was measured, and echocardiography was performed to diagnose dilated
      cardiomyopathy (DCM). RESULTS: In total sixty-one patients (17%) fulfilled the
      criteria for DCM, whereas 283 patients (78%) had an elevated NT-pro BNP. The
      sensitivity of NT-proBNP for DCM in patients or carriers was 85%, the specificity
      23%, area under the ROC-curve = 0.56. In the specified subgroups there was also
      no association. CONCLUSION: Measurement of NT-pro BNP in patients suffering from
      Duchenne or Becker muscular dystrophy and carriers does not distinguish between
      those with and without dilated cardiomyopathy.

PMID- 23870373
TI  - A comparison of trends in research into home care services in Japan and Korea.
AB  - BACKGROUND: The purpose of this study is to compare of the research trends for
      home care services in Japan and the Republic of Korea (Korea). In particular, it
      was compared as the research design, the method of data collection, and key words
      by literature review. METHODS: Original articles on home care services were
      selected from Japanese and Korean journals published from the year of 2004 to
      2008. The articles were classified, and compared in terms of the number of
      articles per year. RESULTS: The research design was quite different. Quantitative
      research design was dominantly conducted in Korea, qualitative research design
      was used same level of design in Japan. In particular, outcome study was shown in
      Korean. CONCLUSIONS: It is suggested that future collaboration be undertaken to
      improve the variety of research design and method especially in both countries
      under the aged society. In addition, it provides information concerning research
      concepts, which can be applied to optimize future home care services.

PMID- 23870374
TI  - Phenomenology, pathography, and the concept of illness.

PMID- 23870375
TI  - Effect of homeopathic preparations of Syzygium jambolanum and Cephalandra indica
      on gastrocnemius muscle of high fat and high fructose-induced type-2 diabetic
      rats.
AB  - BACKGROUND: Homeopathy is a holistic method of treatment that uses microdoses of
      natural substances originating from plants, minerals, or animal parts. Syzygium
      jambolanum and Cephalandra indica are used in homeopathy for treatment of type-2
      diabetes. However, the molecular mechanisms responsible for such effects are not
      known. METHODS: Homeopathic preparations of S. jambolanum and C. indica in mother
      tincture, 6c and 30c were used to examine the molecular mechanism of antidiabetic
      effects in the skeletal muscle of rats with high fat and fructose-induced type-2
      diabetes mellitus. After 30 days treatment, fasting blood glucose, serum insulin
      and insulin signaling molecules in the skeletal muscle (gastrocnemius) were
      measured. RESULTS: Diabetic rats showed a significant decrease in serum insulin
      and lipid profile as well as low levels of insulin receptor (IR), v-akt murine
      thymoma viral oncogene homolog (Akt), p-Akt(ser473) and glucose transporter-4
      (GLUT4) protein expression (p < 0.05) with a significant increase in fasting
      blood glucose level (p < 0.05) compared to the control group. Treatment with
      homeopathic remedies significantly increased the serum insulin and expression of
      these proteins (p < 0.05) with a significant decrease in fasting blood glucose (p
      < 0.05) compared to diabetic rats. CONCLUSIONS: In the present study homeopathic
      preparations of S. jambolanum and C. indica, including ultramolecular dilutions
      exhibit antidiabetic effects, improving insulin action through activation of
      insulin signaling molecules in skeletal muscle of type-2 diabetic rats.

PMID- 23870376
TI  - Preliminary investigation on ultra high diluted B. vulgaris in experimental
      urolithiasis.
AB  - PURPOSE: The study focuses on the anti-urolithiasis potential of ultra-diluted
      homeopathic potency of Berberis vulgaris (B. vulgaris) root bark, commonly used
      in homeopathic system to treat renal calculi. METHODOLOGY: B. vulgaris root bark
      (200c, 20 MUl/100 g body weight/day, p.o, for 28 days) was tested in an animal
      model of urolithiasis. Urolithiasis was induced in male Wistar rats by adding
      0.75% ethylene glycol (EG) to drinking water. Urine and serum samples were
      analyzed for calcium, magnesium, phosphorus, uric acid and creatinine. Enzymic
      makers of renal damage (alkaline phosphatase, lactate dehydrogenase, leucine
      aminopeptidase and gamma-glutamyl transpeptidase) were assessed in kidney and
      urine. Renal tissues were analyzed for oxalate content. RESULTS: Administration
      of EG to rats increased the levels of the stone-forming constituents calcium,
      phosphorus and uric acid, in urine. Levels were normalized by B. vulgaris
      treatment. The decrease in the urolithiasis inhibitor magnesium in urine was
      prevented by treatment with B. vulgaris. Serum creatinine levels were largely
      normalized by B. vulgaris treatment. Hyperoxaluria induced renal damage was
      evident from the decreased activities of tissue marker enzymes and an apparent
      escalation in their activity in the urine in control animals; this was prevented
      by B. vulgaris treatment. CONCLUSION: Homeopathic B. vulgaris root bark has
      strong anti-urolithiasis potential at ultra-diluted dose.

PMID- 23870377
TI  - Stimulative influence of germination and growth of maize seedlings originating
      from aged seeds by 2,4-D potencies.
AB  - BACKGROUND: The 2,4-D (2,4-dichlorophenoxyacetic acid) is using as a growth
      regulator in tissue culture media. Maize seeds have poor ability to maintain
      germination rate in the long term. OBJECTIVE: To examine the possible restorative
      effect of homeopathic 2,4-D potencies on maize seedlings originating from seeds
      damaged by accelerated aging. METHODS: Seeds of four maize lines were subjected
      to accelerated aging stress treatment. Seed samples were treated with distilled
      water (control) and a range of potencies of 2,4-D: 3C, 3.75C, 4.5C, 5.25C and 6C.
      The germination capacity, fresh substance (FS) and length of root and shoot were
      determined. Hydrolysis and biosynthesis, GSH/GSSG ratio and redox capacity were
      calculated. RESULTS: Induced seed aging decreased germination rate and growth of
      seedlings. 2,4-D potencies did not have a statistically significant effect on
      germination. However, there were statistically significant effects on FS
      production, root and shoot length and redox capacity. The 3C potency had the
      largest effect on the FS accumulation, 4.5C increased root and shoot length,
      compared to control (statistically significant). The GSH/GSSG ratio and the redox
      capacity were decreased by aging. The 3C and 4.5C potencies tended to reverse the
      GSH/GSSG ratio (statistically significant) in the root and shoot, (i.e., shifted
      the redox balance to the reduced state). CONCLUSION: Homeopathic potencies of 2,4
      D appear to have a beneficial effect on artificially aged maize seeds: they
      stimulate growth through better substance conversion from seed rest, and shift
      the redox capacity towards a reduced environment. Further work is required to
      determine if this is an useful means of improving maize seed germination and
      growth.

PMID- 23870378
TI  - Homeopathic treatment of patients with influenza-like illness during the 2009
      A/H1N1 influenza pandemic in India.
AB  - INTRODUCTION: We conducted a prospective, multi-centre, data collection survey of
      homeopathic practice in treatment of influenza-like illness in India during the
      2009 pandemic of A/H1N1 influenza ('swine flu', SF). AIMS: To survey the practice
      of homeopathic practitioners in India in the management of SF, with respect to:
      (a) patients' symptoms at presentation and at follow-up (FU) consultation; (b)
      homeopathic medicines prescribed. METHODS: Data collection took place from
      October 2009 to February 2010, at the peak of the pandemic. All patients
      satisfying the minimum diagnostic symptoms of SF were eligible for inclusion.
      Data per appointment (in person or by telephone) were recorded by practitioners
      in spreadsheet format. All records were anonymised and included: whether patient
      was immunised against A/H1N1; influenza symptoms at consultation; the homeopathic
      medicine/s prescribed; whether antiviral medicine prescribed. RESULTS: Twenty
      three homeopathic physicians contributed to data collection. At the first
      appointment, 1126 patients had valid SF symptoms. A total of 89 different
      combinations of SF symptoms was observed, the most common being temperature >38
      degrees C + cough + runny nose (n = 170; 15.1%). A total of 44 different remedies
      (or combinations of remedies) were used at these first appointments, the most
      frequently prescribed being Arsenicum album (n = 265; 23.5%). For a total of 99
      FU appointments with valid SF symptoms, Arsenicum album was prescribed most
      frequently overall (n = 28; 28.0%). CONCLUSIONS: In our sample, the 2009 A/H1N1
      influenza pandemic in India was characterised by several prominent symptoms and
      symptom/medicine associations, particularly temperature >38 degrees C + cough +
      runny nose, associated with Arsenicum album. Future studies should collect
      additional keynote prescribing symptoms that influence the choice of homeopathic
      medicine.

PMID- 23870379
TI  - Homeopathic drug therapy. Homeopathy in Chikungunya Fever and Post-Chikungunya
      Chronic Arthritis: an observational study.
AB  - OBJECTIVES: To observe the effect of homeopathic therapy in Chikungunya Fever
      (CF) and in Post-Chikungunya Chronic Arthritis (PCCA) in a primary health care
      setting. METHODS: A prospective observational study was conducted at Delhi
      Government Homeopathic Dispensary, Aali Village, New Delhi, India, for a period
      of 6 months, from 1st October 2010 to 31st March 2011. 126 patients (75 CF, 51
      PCCA) were enrolled based on predefined inclusion criteria. A single homeopathic
      medicine was prescribed for each patient after case taking with the help of
      Materia Medica and/or Repertory. Results were evaluated on the basis of visual
      analogue scale and symptom scores. RESULTS: Complete recovery was seen in 84.5%
      CF cases in a mean time of 6.8 days. 90% cases of PCCA recovered completely in a
      mean time of 32.5 days. CONCLUSION: Homeopathic therapy may be effective in CF
      and PCCA. A randomized controlled trial should be considered.

PMID- 23870380
TI  - Homeopathy in rural Australian primary health care: a survey of general
      practitioner referral and practice in rural and regional New South Wales,
      Australia.
AB  - INTRODUCTION: Homeopathy has attracted considerable recent attention from the
      Australian conventional medical community. However, despite such increased
      attention there has been little exploration of the interface between homeopathy
      and Australian conventional medical practice. This article addresses this
      research gap by exploring homeopathic practice and referral by rural and regional
      Australian general practitioners (GPs). MATERIALS AND METHODS: A 27-item
      questionnaire was sent to all 1486 GPs currently practising in rural and regional
      New South Wales, Australia (response rate 40.7%). RESULTS: Few GPs in this study
      utilised homeopathy in their personal practice, with only 0.5% of GPs prescribing
      homeopathy in the past 12 months, and 8.5% referring patients for homeopathic
      treatment at least a few times over the past 12 months. Nearly two-thirds of GPs
      (63.9%) reported that they would not refer for homeopathy under any
      circumstances. Being in a remote location, receiving patient requests for
      homeopathy, observing positive responses from homeopathy previously, using
      complementary and alternative medicine (CAM) practitioners as information
      sources, higher levels of knowledge of homeopathy, and being interested in
      increasing CAM knowledge were all independently predictive of increased referral
      to homeopathy amongst GPs in this study. GPs in this study were less likely to
      refer to homeopathy if they used peer-reviewed literature as the major source of
      their information on CAM. CONCLUSIONS: Homeopathy is not integrated significantly
      in rural general practice either via GP utilisation or referral. There is
      significant opposition to homeopathy referral amongst rural and regional GPs,
      though some level of interaction with homeopathic providers exists.

PMID- 23870381
TI  - Hepatitis C Nosode: The preparation and homeopathic pathogenetic trial.
AB  - BACKGROUND: A double blind, randomized placebo controlled homeopathic
      pathogenetic trial (proving) of Hepatitis C (Hep C) nosode was conducted with the
      aim to introduce the new nosode in homeopathic pharmacopeia. METHOD:
      Documentation included approval by Ethics Committee, Informed Consent Form,
      Laboratory investigations, safety and ethical measures. The volunteers were
      trained to write data in prescribed diaries and data were analyzed. A fifteen
      step method was used in the preparation of Hep C nosode (genotype I and III),
      allowing future preparation of an identical nosode. 22 volunteers were entered,
      15 received Hep C nosode in 30c potency, 7 received placebo, once a week for four
      weeks. RESULTS: The Hep C nosode was associated with qualitatively and
      quantitatively distinct symptoms, which can be applied in clinical practice. A
      significantly higher incidence of pathogenetic effect of homeopathic medicine
      compared to placebo was observed. Safety was documented. The nosode produced
      symptoms comparable with Hep C disease. CONCLUSION: An improved method of nosode
      preparation was used. A double blind, randomized placebo controlled pathogenetic
      trial of the Hep C nosode generated guiding symptoms, which may facilitate its
      prescription in practice. The nosode should be further explored for the treatment
      of immunologically mediated diseases, infections including Hep C, fibrotic
      pathology and chronic inflammatory disorders.

PMID- 23870382
TI  - Immunomodulatory drugs (natalizumab), worsening of multiple sclerosis, rebound
      effect and similitude.
AB  - BACKGROUND: Homeopathic treatment is based on the principle of similitude ('like
      cures like') administering to sick individuals substances that cause similar
      symptoms in healthy individuals, employing the paradoxical or biphasic action of
      the organism as therapeutic response. This homeostatic, vital or secondary action
      of the organism is scientifically explained by the rebound effect of drugs,
      resulting in worsening of symptoms after enantiopathic treatment withdrawal.
      Natalizumab reduces relapses in patients with active multiple sclerosis (MS), but
      recent studies report severe worsening of MS after suspension of treatment, as a
      consequence of the rebound effect. METHOD: Extending this source of evidence,
      this work reviews research that demonstrates secondary worsening of MS after
      discontinuation of natalizumab, a human monoclonal antibody that suppresses the
      disease inflammatory activity as primary action. RESULTS: Several studies refer
      to the immune reconstitution inflammatory syndrome (IRIS) as a plausible
      explanation of reactivation of MS after withdrawal of natalizumab: a rebound
      effect or secondary action of the organism in response to the primary
      immunosuppression caused by the drug. CONCLUSION: Relapses of MS after
      discontinuation of natalizumab treatment indicate rebound of disease activity,
      supporting the homeopathic principle and warning healthcare professionals about
      this serious iatrogenic event.

PMID- 23870383
TI  - Phenomenology and homeopathy.
AB  - There is a great overlap between the way of seeing the world in clinical
      homeopathy and in the technical philosophical system known as phenomenology. A
      knowledge of phenomenologic principles reveals Hahnemann to have been an
      unwitting phenomenologist. The ideas of phenomenology as applied to medicine show
      that homeopathy is the ideal medical system to fulfill the goals of coming ever
      closer to true patient concerns and experience of illness. 

PMID- 23870384
TI  - The outcome of patients with low risk gestational trophoblastic neoplasia treated
      with single agent intramuscular methotrexate and oral folinic acid.
AB  - BACKGROUND: Gestational trophoblastic neoplasia (GTN) persisting despite local
      treatment requires chemotherapy. In 2000, the revised International Federation of
      Gynaecology and Obstetrics (FIGO)/World Health Organisation (WHO) staging system
      was introduced, classifying patients as at 'low' or 'high' risk for resistance to
      single agent treatment. PATIENTS AND METHODS: We have evaluated the complete
      response rates of patients with low risk GTN treated with 2 weekly intramuscular
      (IM) methotrexate 50mg four doses days 1, 3, 5, 7 and oral folinic acid 15 mg
      days 2, 4, 6, 8 (MTX/FA). Patient data between January 2000 and December 2011
      were collated and the relationships between FIGO/WHO risk score and outcomes
      evaluated. RESULTS: Two hundred and eighty nine patients were treated with single
      agent IM MTX/FA and assessed for treatment response. 29/36 (81%) patients with a
      FIGO/WHO total score of 6 developed resistance to MTX/FA compared with 87/253
      (34%) patients with a score of 0-5 (p <= 0.0001). Significantly higher rates of
      resistance were found for patients with an hCG level of >100,000 iu/l compared to
      an hCG level of <100,000 iu/l (84% versus 34% p <= 0.0001). All patients were
      eventually cured with chemotherapy or surgical salvage. CONCLUSIONS: Patients
      with low risk GTN that have a FIGO/WHO score of 6 or hCG level of >100,000 iu/l
      have high rates of resistance to MTX/FA and require further treatment. Revision
      of the FIGO/WHO scoring system may be appropriate to enable selection of more
      effective first line chemotherapy.

PMID- 23870385
TI  - Recent advances in melanoma systemic therapy. BRAF inhibitors, CTLA4 antibodies
      and beyond.
AB  - Metastatic melanoma has a poor prognosis and until recently systemic therapy was
      ineffective. Advances in the understanding of tumour biology and immune
      regulation have led to the development of targeted agents that have changed
      clinical practice, with further improvements expected with new compounds and
      combinations. The first major advance was the development of selective mitogen
      activated protein (MAP) kinase inhibitors (BRAF and MEK inhibitors) and immune
      checkpoint blockade with a CTLA4 antibody (ipilimumab). These drugs proved vastly
      superior to conventional chemotherapy, however response, resistance and toxicity
      were limitations. The second major advance is the development of other immune
      checkpoint blocking agents, including PD-1 and PD-L1 antibodies, and the use of
      BRAF and MEK inhibitors in combination, with a higher proportion of durable
      responses coupled with less toxicity. In an effort to improve outcomes for
      patients with melanoma further, trials are underway examining the combination of
      MAPK inhibitors, immunotherapies and other pathway inhibitors and adjuvant
      studies of many of these agents have commenced. 

PMID- 23870386
TI  - [Obstructive sleep apnea syndrome in children].
AB  - Obstructive sleep apnea (OSA) is highly prevalent in school-aged children.
      Tonsillar and/or adenoids hypertrophy is the most common etiology of OSA in
      children. OSA has been associated with sleep quality disturbance (frequent
      arousals) and nocturnal gas-exchange abnormalities (hypoxemia and sometimes
      hypercapnia), complicated with a large array of negative health outcomes. The
      clinical symptoms are not able to distinguish primary snoring from OSA.
      Polysomnography remains the gold standard for the diagnosis of sleep disordered
      breathing, but the demand is increasing for this highly technical sleep test. So,
      some other simpler diagnostic methods are available, as respiratory polygraphy,
      but need to be validated in children. Treatment of OSA in children must be based
      on a mutlidisciplinary approach with pediatricians, ENT surgeons and
      orthodontists. 

PMID- 23870387
TI  - Alternate stresses and temperature variation as factors of influence of
      ultrasonic vibration on mechanical and functional properties of shape memory
      alloys.
AB  - It is known that the main factors in a variation in the shape memory alloy
      properties under insonation are heating of the material and alternate stresses
      action. In the present work the experimental study of the mechanical behaviour
      and functional properties of shape memory alloy under the action of alternate
      stresses and varying temperature was carried out. The data obtained had
      demonstrated that an increase in temperature of the sample resulted in a decrease
      or increase in deformation stress depending on the structural state of the TiNi
      sample. It was shown that in the case of the alloy in the martensitic state, a
      decrease in stress was observed, and on the other hand, in the austenitic state
      an increase in stress took place. It was found that action of alternate stresses
      led to appearance of strain jumps on the strain-temperature curves during cooling
      and heating the sample through the temperature range of martensitic
      transformation under the constant stress. The value of the strain jumps depended
      on the amplitude of alternate stresses and the completeness of martensitic
      transformation. It was shown that the heat action of ultrasonic vibration to the
      mechanical behaviour of shape memory alloys was due to the non-monotonic
      dependence of yield stress on the temperature. The force action of ultrasonic
      vibration to the functional properties was caused by formation of additional
      oriented martensite. 

PMID- 23870388
TI  - Acoustic source localization.
AB  - In this article different techniques for localizing acoustic sources are
      described and the advantages/disadvantages of these techniques are discussed.
      Some source localization techniques are restricted to isotropic structures while
      other methods can be applied to anisotropic structures as well. Some techniques
      require precise knowledge of the direction dependent velocity profiles in the
      anisotropic body while other techniques do not require that knowledge. Some
      methods require accurate values of the time of arrival of the acoustic waves at
      the receivers while other techniques can function without that information.
      Published papers introducing various techniques emphasize the advantages of the
      introduced techniques while ignoring and often not mentioning the limitations and
      weaknesses of the new techniques. What is lacking in the literature is a
      comprehensive review and comparison of the available techniques; this article
      attempts to do that. After reviewing various techniques the paper concludes which
      source localization technique should be most effective for what type of structure
      and what the current research needs are. 

PMID- 23870389
TI  - Aberrant placental immune parameters in the feline immunodeficiency virus (FIV)
      infected cat suggest virus-induced changes in T cell function.
AB  - BACKGROUND: Immune activity during pregnancy must be tightly regulated to ensure
      successful pregnancy. This regulation includes the suppression of inflammatory
      activity that could target the semi-allogeneic fetus. Tregs are
      immunosuppressive; Th17 cells are pro-inflammatory. A precise balance in the two
      cell populations is critical to pregnancy maintenance, while dysregulation in
      this balance accompanies compromised pregnancy in humans and mice. FIV is known
      to target Tregs preferentially in the infected cat. Therefore, it may be
      hypothesized that FIV infection alters the placental Treg/Th17 cell balance
      resulting in aberrant immunomodulator expression by these cells and consequent
      pregnancy perturbation. METHODS: RNA was purified from random sections of whole
      placental tissues collected from both uninfected and FIV-infected queens at early
      pregnancy, including tissues from viable and nonviable fetuses. Real time qPCR
      was performed to quantify expression of intranuclear markers of Tregs (FoxP3) and
      Th17 cells (RORgamma); cytokine products of Tregs (IL-10 and TGF-beta), Th17
      cells (IL-2, IL-6, and IL-17a), and macrophages (IL-1beta); and the FIV gag gene.
      Pairwise comparisons were made to evaluate coexpression patterns between the
      cytokines and between the cytokines and the virus. RESULTS: Both FoxP3 and
      RORgamma were reduced in placentas of infected animals. Neither infection status
      nor fetal viability affected placental expression of IL-1beta. However, fetal
      nonviability was associated with reduced levels of all other cytokines. Infection
      and fetal nonviability impacted coexpression of various cytokine pairs. No
      obvious bias toward Treg or Th17 cells was observed. CONCLUSIONS: FIV infection
      coupled with fetal nonviability alters expression patterns of T cell cytokines.
      These data suggest that functionally altered placental T cell leukocyte
      populations may occur in the infected queen and possibly contribute to fetal
      nonviability.

PMID- 23870390
TI  - The impact of race on outcomes following emergency surgery: an American College
      of Surgeons National Surgical Quality Improvement Program assessment.
AB  - BACKGROUND: Despite significant evolutions in health care, outcome discrepancies
      exist among demographic cohorts. We sought to determine the impact of race on
      emergency surgery outcomes. METHODS: This is a retrospective review of the
      American College of Surgeons National Surgical Quality Improvement Program
      database (2005 through 2009) for all patients aged >=16 years undergoing
      emergency abdominal surgery. Primary outcomes included morbidity and mortality.
      RESULTS: We identified 75,280 patients (mean age 48.2 +/- 19.9 years, 51.7%
      female; 79% white, 9.9% black, 5.0% Hispanic, 3.7% Asian, 1.3% American Indian or
      Alaskan, .2% Pacific Islander). Annual rates of emergency operations ranged from
      7.3% to 8.5% (P = .22). The overall complication (18.6%) and mortality rate
      (4.6%) was highest in the black population (24.3%, 5.3%) followed by whites
      (18.7%, 4.6%), with the lowest rate in Hispanic (11.7%, 1.8%) and Pacific
      Islander populations (10.2%, 1.8%; P < .001). Compared with whites, blacks had a
      1.25-fold (1.17 to 1.34; P < .001) increased risk of complications, but similar
      mortality (P = .168). When combining minorities, overall complications were 1.059
      fold (1.004 to 1.12; P = .034) higher, however, mortality was reduced 1.7-fold
      (1.07 to 1.34; P = .001). CONCLUSIONS: Following emergency abdominal surgery,
      minority race is independently associated with increased complications and
      reduced mortality.

PMID- 23870391
TI  - Perforations following endoscopic retrograde cholangiopancreatography: a single
      institution experience and surgical recommendations.
AB  - BACKGROUND: Perforation after endoscopic retrograde cholangiopancreatography
      (ERCP) is uncommon, and its management is dependent on the mechanism and the
      graded classification of injury. METHODS: Records of patients undergoing ERCP
      were analyzed over a 16-year period, patterning the types of injuries, diagnosis,
      management, and patient outcome. Type I injuries damage the medial or lateral
      duodenal wall before sphincter cannulation. Type II injuries are periampullary
      and occur as a result of a precut or a papillotomy. Type III injuries occur
      secondary to guidewire insertion or stone extraction from the common bile duct.
      Type IV injuries are probably microperforations that are noted on excessive
      insufflation during and after ERCP withdrawal. RESULTS: Between 1995 and 2011, 27
      perforations were identified from 1,638 ERCP procedures (1.6%). Nearly half of
      the procedures were regarded as difficult by the endoscopist, with 70% of the
      ERCPs (19 of 27) being for therapeutic indications. There were 5 type I, 12 type
      II, 5 type III, and 5 type IV perforations, of which 18 cases were diagnosed at
      the time of ERCP. Delayed diagnosis of type I perforations that were associated
      with free intraperitoneal air and contrast leakage proved fatal. Most type II
      perforations required immediate surgery with pyloric exclusion; delayed surgery
      with simple drainage had a high mortality rate. Most type III and type IV
      injuries can successfully be managed conservatively without delayed sepsis.
      CONCLUSIONS: In perforation, the mechanism of injury during ERCP predicts the
      need for surgical management. Type I and type II injuries require early diagnosis
      and aggressive surgery, whereas type III and type IV injuries may be managed
      conservatively.

PMID- 23870392
TI  - Patient surveillance after initial breast cancer therapy: variation by physician
      specialty.
AB  - BACKGROUND: American Society of Clinical Oncology (ASCO) guidelines recommend
      only office visits and mammograms as the primary modalities for patient
      surveillance after treatment for breast carcinoma. This study aimed to quantify
      differences in posttreatment surveillance among medical oncologists, radiation
      oncologists, and surgeons. METHODS: We e-mailed a survey to the 3,245 ASCO
      members who identified themselves as having breast cancer as a major focus of
      their practices. Questions assessed the frequency of use of 12 specific
      surveillance modalities for 5 posttreatment years. RESULTS: Of 1,012 total
      responses, 846 were evaluable: 5% from radiation oncologists, 70% from medical
      oncologists, and 10% from surgeons; 15% were unspecified. Marked variation in
      surveillance practices were noted within each specialty and among specialties.
      CONCLUSION: There are notable variations in surveillance intensity. This suggests
      overuse or underuse or misuse of scarce medical resources.

PMID- 23870393
TI  - Passing the torch: evaluating exportability of a violence intervention program.
AB  - BACKGROUND: A violence intervention program (VIP) developed at our trauma center
      resulted in a reduction of injury recidivism to 4% from a historical rate of 16%.
      Our aim was to investigate the feasibility of exporting our program to another
      trauma center by examining rates of and identifying potential barriers to
      recruitment, enrollment, and impact. We hypothesized that our VIP is feasible at
      another trauma center and successfully meets needs associated with risk
      reduction. METHODS: In January 2010, we introduced our VIP to another trauma
      center. To assess exportability of our program, we used a standard model of
      program evaluation for VIPs promoted by the Centers for Disease Control and
      Prevention. Specifically, the process and impact portions of the model evaluation
      were performed in this comparative analysis over a 1-year period. Recruitment,
      enrollment (process), and success at meeting risk reduction needs (impact) were
      our outcomes. This included patient and case manager characteristics in addition
      to rates at which eligible patients were approached and enrolled. These variables
      were compared using the Wilcoxon rank-sum and chi-square tests. RESULTS: During
      the study period, 155 patients were eligible for inclusion at the exported
      program compared with 119 at the original VIP. Rates at which eligible patients
      were approached at the exported program were significantly lower than the
      original program (44% vs 92%, P = .04). Rates at which approached patients were
      enrolled were also significantly lower (21% vs 55%, P = .002). The difference was
      associated with the time of injury and hospital length of stay because 40% of
      eligible patients were missed if injury occurred during a weekend and 70% were
      missed if the length of stay was less than or equal to 48 hours at the exported
      program. A cultural match between the client and case manager was assessed by
      race/ethnicity and language spoken; 2 of the 3 case managers at our site are
      Latino and bilingual and the other is black, whereas the 1 case manager at the
      exported program is black and monolingual. Cultural match was 91% versus 47%,
      respectively (P < .05). IMPACT: Both programs met more than 50% of identified
      client needs in several categories. CONCLUSIONS: Program exportation is based on
      the replication of both the program model and the program infrastructure. The
      data in our study support success of the program model (case management process)
      at our export site, but the actual program infrastructure was not successfully
      exported to this hospital.

PMID- 23870394
TI  - The scientific dichotomy and the question of evidence.

PMID- 23870396
TI  - Should surgeons know the costs of the implants they use?

PMID- 23870395
TI  - Complications following the extended lateral approach for calcaneal fractures do
      not influence mid- to long-term outcome.
AB  - BACKGROUND AND AIM: Open reduction and internal fixation (ORIF) of intra
      articular calcaneal fractures through an extended lateral approach is frequently
      accompanied by a high complication rate. However, ORIF currently provides the
      best long-term clinical results. The aim of this study was twofold: (1) to
      evaluate both mid- to long-term clinical and radiological results of a
      consecutive series treated by ORIF and (2) to determine the influence of short
      term complications on long-term clinical outcome. METHODS: Patients with a
      displaced intra-articular calcaneal fracture, treated with ORIF, through an
      extended lateral approach, in a level-2 trauma centre between 1995 and 2008 were
      evaluated for the study. The long-term functional outcome (American Orthopaedic
      Foot & Ankle Society (AOFAS), 36-Item Short-Form Health Survey (SF-36) and Visual
      Analogue Scale (VAS)) and radiographic results (e.g., Bohler and Gissane angle,
      height, width and joint reduction) were determined. Short- and long-term
      complications were documented. RESULTS: A total of 57 patients matched the
      inclusion criteria, from which 39 patients agreed to participate in this study
      (68%). The median follow-up was 6.5 years (range 2-16 years). Based on the AOFAS
      hindfoot score, 74% of the patients had a good-to-excellent long-term clinical
      result. Radiological results were satisfying with a median postoperative Bohler
      angle of 26 degrees  and 25 degrees  at follow-up. Complications occurred in 32%
      of all patients; mainly wound-healing problems were noted. Short-term
      complications did not influence mid- to long-term clinical results (p>0.05).
      Anatomic reconstruction of the calcaneus was associated with improved long-term
      clinical results (p<0.05). CONCLUSION: Despite the high complication rate
      following ORIF of a calcaneal fracture, complications do not affect mid- to long
      term clinical outcome. Surgical treatment should focus on restoring the anatomy.
      LEVEL OF EVIDENCE: Therapeutic level IV.

PMID- 23870397
TI  - Technique to aid elastic nailing of paediatric femoral shaft fractures.

PMID- 23870398
TI  - Three-dimensional computed tomography angiography for the preoperative evaluation
      of coronary artery disease in lung cancer patients.
AB  - BACKGROUND: The number of elderly patients undergoing surgery for lung cancer is
      increasing. In this study, we assessed the usefulness of three-dimensional
      computed tomographicangiography (3D-CTA) for the detection of coronary disease in
      the elderly before surgical intervention for lung cancer. METHODS: One hundred
      twenty patients admitted to our institution for lung cancer resection were
      enrolled in the study. 3D-CTA was performed in all 120 patients. RESULTS: Seventy
      one patients had normal findings, and forty-nine patients showed coronary
      stenosis on 3D-CTA examination. Among the latter 49 patients, 24 with slight
      stenosis underwent lung tumor resection, 23 had coronary angiography for severe
      stenosis before lung surgery and 2 were not eligible for lung resection because
      of very severe coronary stenosis. The diagnostic value of 3D-CTA was better than
      conventional CT. CONCLUSIONS: This study suggests the usefulness of 3D-CTA for
      the preoperative diagnosis of coronary ischemic disease in elderly lung cancer
      patients.

PMID- 23870399
TI  - Benign and malignant ovarian steroid cell tumors, not otherwise specified: case
      studies, comparison, and review of the literature.
AB  - Ovarian steroid cell tumors, not otherwise specified (NOS) are rare sex cord
      stromal tumors of the ovary with malignant potential. So far only a few cases
      were reported in English literature through the Pubmed search. Here we report two
      cases of such tumor, one was benign (first case underwent laparoscopic
      cystectomy) and the other was malignant (died 10 months later after initial
      diagnosis), both presented with amenorrhea and clinical signs or symptoms of
      virilization. In malignant case, we provided evidence (tumor embolus) in addition
      to the reported five characteristics associated with malignancy. On further
      evaluation, laboratory investigations revealed hyperandrogenism in the male
      range, while follicle stimulating hormone (FSH) and luteinising hormone (LH)
      levels were within normal limits. Various aspects of the presentation, diagnosis,
      and treatment of these tumors are discussed. 

PMID- 23870401
TI  - The influence of inelastic scattering on EFTEM images--exemplified at 20 kV for
      graphene and silicon.
AB  - We present model-based image simulations for zero-loss and plasmon-loss filtered
      images at 20 kV for graphene and silicon based on the mutual coherence approach.
      In addition, a new approximation for the mixed dynamic form factor is introduced.
      In our calculation multiple elastic scattering and one inelastic scattering are
      taken into account. The simulation shows that even the intensity of zero-loss
      filtered image is attenuated by the interference between inelastically scattered
      waves. Moreover, the intensity of plasmon-loss filtered images cannot be
      neglected, either.

PMID- 23870400
TI  - Suppression of genetic recombination in the pseudoautosomal region and at
      subtelomeres in mice with a hypomorphic Spo11 allele.
AB  - BACKGROUND: Homologous recombination is the key process that generates genetic
      diversity and drives evolution. SPO11 protein triggers recombination by
      introducing DNA double stranded breaks at discreet areas of the genome called
      recombination hotspots. The hotspot locations are largely determined by the DNA
      binding specificity of the PRDM9 protein in human, mice and most other mammals.
      In budding yeast Saccharomyces cerevisae, which lacks a Prdm9 gene, meiotic
      breaks are formed opportunistically in the regions of accessible chromatin,
      primarily at gene promoters. The genome-wide distribution of hotspots in this
      organism can be altered by tethering Spo11 protein to Gal4 recognition sequences
      in the strain expressing Spo11 attached to the DNA binding domain of the Gal4
      transcription factor. To establish whether similar re-targeting of meiotic breaks
      can be achieved in PRDM9-containing organisms we have generated a Gal4BD-Spo11
      mouse that expresses SPO11 protein joined to the DNA binding domain of yeast
      Gal4. RESULTS: We have mapped the genome-wide distribution of the recombination
      initiation sites in the Gal4BD-Spo11 mice. More than two hundred of the hotspots
      in these mice were novel and were likely defined by Gal4BD, as the Gal4 consensus
      motif was clustered around the centers in these hotspots. Surprisingly, meiotic
      DNA breaks in the Gal4BD-Spo11 mice were significantly depleted near the ends of
      chromosomes. The effect is particularly striking at the pseudoautosomal region of
      the X and Y chromosomes - normally the hottest region in the genome. CONCLUSIONS:
      Our data suggest that specific, yet-unidentified factors influence the initiation
      of meiotic recombination at subtelomeric chromosomal regions.

PMID- 23870402
TI  - Development of novel real-time TaqMan((r)) PCR assays for the species and sex
      identification of otter (Lutra lutra) and their application to noninvasive
      genetic monitoring.
AB  - Developing strategies to maintain biodiversity requires baseline information on
      the current status of each individual species. The development of genetic
      techniques and their application to noninvasively collected samples have the
      potential to yield information on the structure of elusive animal populations and
      so are important tools in conservation management. Using DNA isolated from faecal
      samples can be challenging owing to low quantity and quality. This study,
      however, presents the development of novel real-time polymerase chain reaction
      assays using fluorescently labelled TaqMan((r)) MGB probes enabling species and
      sex identification of Eurasian otter (Lutra lutra) spraints (faeces). These
      assays can also be used in determining an optimum microsatellite panel and can be
      employed as cost-saving screening tools for downstream genetic testing including
      microsatellite genotyping and haplotype analysis. The techniques are shown to
      work efficiently with L. lutra DNA isolated from tissue, hair, spraint, blood and
      anal jelly samples. 

PMID- 23870404
TI  - Simultaneous measurement of two enzyme activities using infrared spectroscopy: A
      comparative evaluation of PARAFAC, TUCKER and N-PLS modeling.
AB  - Enzymes are used in many processes to release fermentable sugars for green
      production of biofuel, or the refinery of biomass for extraction of functional
      food ingredients such as pectin or prebiotic oligosaccharides. The complex
      biomasses may, however, require a multitude of specific enzymes which are active
      on specific substrates generating a multitude of products. In this paper we use
      the plant polymer, pectin, to present a method to quantify enzyme activity of two
      pectolytic enzymes by monitoring their superimposed spectral evolutions
      simultaneously. The data is analyzed by three chemometric multiway methods,
      namely PARAFAC, TUCKER3 and N-PLS, to establish simultaneous enzyme activity
      assays for pectin lyase and pectin methyl esterase. Correlation coefficients
      Rpred(2) for prediction test sets are 0.48, 0.96 and 0.96 for pectin lyase and
      0.70, 0.89 and 0.89 for pectin methyl esterase, respectively. The retrieved
      models are compared and prediction test sets show that especially TUCKER3
      performs well, even in comparison to the supervised regression method N-PLS. 

PMID- 23870403
TI  - Analytical chemistry of the persistent organic pollutants identified in the
      Stockholm Convention: A review.
AB  - Persistent organic pollutants (POPs) are major environmental concern due to their
      persistence, long-range transportability, bio-accumulation and potentially
      adverse effects on living organisms. Analytical chemistry plays an essential role
      in the measurement of POPs and provides important information on their
      distribution and environmental transformations. Much effort has been devoted
      during the last two decades to the development of faster, safer, more reliable
      and more sensitive analytical techniques for these pollutants. Since the
      Stockholm Convention (SC) on POPs was adopted 12 years ago, analytical methods
      have been extensively developed. This review article introduces recent analytical
      techniques and applications for the determination of POPs in environmental and
      biota samples, and summarizes the extraction, separation and instrumental
      analyses of the halogenated POPs. Also, this review covers important aspects for
      the analyses of SC POPs (e.g. lipid determination and quality assurance/quality
      control (QA/QC)), and finally discusses future trends for improving the POPs
      analyses and for potential new POPs. 

PMID- 23870405
TI  - Electrochemical immunoassay for thyroxine detection using cascade catalysis as
      signal amplified enhancer and multi-functionalized magnetic graphene sphere as
      signal tag.
AB  - This paper constructed a reusable electrochemical immunosensor for the detection
      of thyroxine at an ultralow concentration using cascade catalysis of cytochrome c
      (Cyt c) and glucose oxidase (GOx) as signal amplified enhancer. It is worth
      pointing out that numerous Cyt c and GOx were firstly carried onto the double
      stranded DNA polymers based on hybridization chain reaction (HCR), and then the
      amplified responses could be achieved by cascade catalysis of Cyt c and GOx
      recycling with the help of glucose. Moreover, multi-functionalized magnetic
      graphene sphere was synthesized and used as signal tag, which not only exhibited
      good mechanical properties, large surface area and an excellent electron transfer
      rate of graphene, but also possessed excellent redox activity and desirable
      magnetic property. With a sandwich-type immunoreaction, the proposed cascade
      catalysis amplification strategy could greatly enhance the sensitivity for the
      detection of thyroxine. Under the optimal conditions, the immunosensor showed a
      wide linear ranged from 0.05pg mL(-1) to 5ng mL(-1) and a low detection limit
      down to 15fg mL(-1). Importantly, the proposed method offers promise for
      reproducible and cost-effective analysis of biological samples.

PMID- 23870406
TI  - Non-conductive nanomaterial enhanced electrochemical response in stripping
      voltammetry: The use of nanostructured magnesium silicate hollow spheres for
      heavy metal ions detection.
AB  - Nanostructured magnesium silicate hollow spheres, one kind of non-conductive
      nanomaterials, were used in heavy metal ions (HMIs) detection with enhanced
      performance for the first time. The detailed study of the enhancing
      electrochemical response in stripping voltammetry for simultaneous detection of
      ultratrace Cd(2+), Pb(2+), Cu(2+) and Hg(2+) was described. Electrochemical
      properties of modified electrodes were characterized by cyclic voltammetry (CV)
      and electrochemical impedance spectroscopy (EIS). The operational parameters
      which have influence on the deposition and stripping of metal ions, such as
      supporting electrolytes, pH value, and deposition time were carefully studied.
      The anodic stripping voltammetric performance toward HMIs was evaluated using
      square wave anodic stripping voltammetry (SWASV) analysis. The detection limits
      achieved (0.186nM, 0.247nM, 0.169nM and 0.375nM for Cd(2+), Pb(2+), Cu(2+) and
      Hg(2+)) are much lower than the guideline values in drinking water given by the
      World Health Organization (WHO). In addition, the interference and stability of
      the modified electrode were also investigated under the optimized conditions. An
      interesting phenomenon of mutual interference between different metal ions was
      observed. Most importantly, the sensitivity of Pb(2+) increased in the presence
      of certain concentrations of other metal ions, such as Cd(2+), Cu(2+) and Hg(2+)
      both individually and simultaneously. The proposed electrochemical sensing method
      is thus expected to open new opportunities to broaden the use of SWASV in
      analysis for detecting HMIs in the environment. 

PMID- 23870407
TI  - Determination of hormones in milk by hollow fiber-based stirring extraction bar
      liquid-liquid microextraction gas chromatography mass spectrometry.
AB  - The hollow fiber-based stirring extraction bar liquid-liquid microextraction was
      applied to the extraction of hormones, including 17-alpha-ethinylestradiol, 17
      alpha-estradiol, estriol, 17-beta-estradiol, estrone, 17-alpha
      hydroxyprogesterone, medroxyprogesterone, progesterone and norethisterone
      acetate, in milk. The present method has the advantages of both hollow fiber
      liquid phase microextraction and stirring bar sorptive extraction. The stirring
      extraction bar was used as both the stirring bar of microextraction, and
      extractor of the analytes, which can make extraction, clean-up and concentration
      be carried out in one step. When the extraction was completed, the stirring
      extraction bar was easy isolated from the extraction system with the magnet.
      Several experimental parameters, including the type of extraction solvent, the
      number of hollow stirring extraction bar, extraction time, stirring speed, ionic
      strength, and desorption conditions were investigated and optimized. The analytes
      in the extract were derived and determined by gas chromatography mass
      spectrometry. Under optimal experimental conditions, good linearity was observed
      in the range of 0.20-20.00ng mL(-1). The limits of detection and quantification
      were in the range of 0.02-0.06ng mL(-1) and 0.07-0.19ng mL(-1), respectively. The
      present method was applied to the analysis of milk samples, and the recoveries of
      analytes were in the range of 93.6-104.6% with the relative standard deviations
      ranging from 1.6% to 6.2% (n=5). The results showed that the present method was a
      rapid and feasible method for the determination of hormones in milk samples.

PMID- 23870409
TI  - Use of a mobile phone for potentiostatic control with low cost paper-based
      microfluidic sensors.
AB  - By exploiting its ability to play sounds, a mobile phone with suitable software
      installed can serve the basic functions of a potentiostat in controlling an
      applied potential to oxidise ECL-active molecules, while the resultant photonic
      signal is monitored using the camera in video mode. In combination with paper
      microfluidic sensors this opens significant new possibilities for low-cost,
      instrument-free sensing. 

PMID- 23870408
TI  - Combination of computational methods, adsorption isotherms and selectivity tests
      for the conception of a mixed non-covalent-semi-covalent molecularly imprinted
      polymer of vanillin.
AB  - A novel molecularly imprinted polymer (MIP) for vanillin was prepared by photo
      initiated polymerization in dichloromethane using a mixed semi-covalent and non
      covalent imprinting strategy. Taking polymerisable syringaldehyde as "dummy"
      template, acrylamide was chosen as functional monomer on B3LYP/6-31+G(d,p)
      density functional theory computational method basis with counterpoise. The
      binding parameters for the recognition of vanillin on imprinted polymers were
      studied with three different isotherm models (Langmuir, bi-Langmuir and Langmuir
      Freundlich) and compared. The results indicate an heterogeneity of binding sites.
      It was found and proved by DFT calculations that the specific binding of vanillin
      in the cavities is due to non-covalent interactions of the template with the
      hydroxyphenyl- and the amide-moieties. The binding geometry of vanillin in the
      MIP cavity was also modelled. The obtained MIP is highly specific for vanillin
      (with an imprinting factor of 7.4) and was successfully applied to the extraction
      of vanillin from vanilla pods, red wine spike with vanillin, natural and
      artificial vanilla sugar with a recovery of 80%. 

PMID- 23870410
TI  - A reliable and environmentally-friendly liquid-chromatographic method for multi
      class determination of fat-soluble UV filters in cosmetic products.
AB  - An environmentally-friendly analytical method for the simultaneous determination
      of 15 fat-soluble ultraviolet (UV) filters currently authorized by the European
      Union regulation on cosmetic products has been developed. The determination was
      performed by liquid chromatography with UV spectrophotometric detection.
      Different parameters, such as type of column, oven temperature, mobile phase
      composition and flow rate were studied. The best chromatographic separation was
      obtained under the following conditions: C18 column set at 60 degrees C and
      gradient ethanol:water (containing 1% formic acid and 20mM of 2-hydroxypropyl
      beta-cyclodextrin) as mobile phase pumped at 1mL min(-1). 2-Hydroxypropyl-beta
      cyclodextrin was added as mobile phase modifier to achieve the complete
      resolution of some of the chromatographic peaks. The 15 target compounds were
      separated in less than 30min. The method was satisfactorily validated by
      analyzing three laboratory-made cosmetic samples besides of eleven commercially
      available cosmetic products containing different combination of the target UV
      filters. Good accordance of the found levels compared with those of the
      laboratory-made samples and those of the commercial samples (when available) was
      achieved. Moreover, excellent recoveries (97-104%) and good intra-day and inter
      day precision values at different concentration levels, besides limits of
      detection values below the MUg mL(-1) level, were obtained. These good analytical
      features, as well as their environmentally-friendly characteristics, make the
      presented method suitable not only for routine analysis in cosmetics industries,
      but also as candidate reference method for sunscreen analysis.

PMID- 23870411
TI  - Listening to Mothers III: the evolving landscape of childbearing women's
      experiences and preferences.

PMID- 23870412
TI  - Overexpression of YAP 1 contributes to progressive features and poor prognosis of
      human urothelial carcinoma of the bladder.
AB  - BACKGROUND: Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo
      pathway, is a key regulator of organ size and a candidate human oncogene in
      multiple tumors. However, the expression dynamics of YAP 1 in urothelial
      carcinoma of the bladder (UCB) and its clinical/prognostic significance are
      unclear. METHODS: In this study, the methods of quantitative real-time polymerase
      chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were
      utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman's
      rank correlation, Kaplan-Meier plots and Cox proportional hazards regression
      model were used to analyze the data. RESULTS: Up-regulated expression of YAP 1
      mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western
      blotting, when compared with their paired normal bladder tissues. By IHC,
      positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86
      (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was
      correlated with poorer differentiation, higher T classification and higher N
      classification (P < 0.05). In univariate survival analysis, a significant
      association between positive expression of YAP 1 and shortened patients' survival
      was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was
      also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P =
      0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P <
      0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003)
      together with pT and pN status (P< 0.05) provided significant independent
      prognostic parameters in multivariate analysis. CONCLUSIONS: Our findings provide
      evidences that positive expression of YAP 1 in UCB may be important in the
      acquisition of an aggressive phenotype, and it is an independent biomarker for
      poor prognosis of patients with UCB.

PMID- 23870413
TI  - Adequacy of opioid analgesic consumption at country, global, and regional levels
      in 2010, its relationship with development level, and changes compared with 2006.
AB  - CONTEXT: In most countries, patients do not have adequate access to opioid
      analgesics because of barriers resulting from the abuse potential of these
      medicines. OBJECTIVES: To provide an analysis for the adequacy of the consumption
      of opioid analgesics for countries and World Health Organization regions in 2010
      as compared with 2006. METHODS: We calculated the Adequacy of Consumption Measure
      using data for 2010 based on a method established by Seya et al. This method
      calculates the morbidity-corrected needs per capita for relevant strong opioid
      analgesics and the actual use for the top 20 Human Development Index countries.
      It determines the adequacy of the consumption for each country, World Health
      Organization region, and the world by comparing the actual consumption with the
      calculated need. Furthermore, the method allows us to calculate the number of
      people living in countries at various levels of adequacy. We compared our
      outcomes with data from Seya et al. for 2006. RESULTS: Most people have no access
      to opioids for pain relief in case of need; 66% of the world population has
      virtually no consumption, 10% very low, 3% low, 4% moderate, and only 7.5%
      adequate. For 8.9%, no data are available. Between 2006 and 2010, 67 countries
      increased the adequacy of opioid consumption per capita. These changes are
      independent of countries' level of development. CONCLUSION: The consumption of
      opioid analgesics remains inadequate in most of the world and, as a result,
      patients with moderate and severe pain do not receive the treatment they need.
      Governments, health organizations, and nongovernmental organizations must
      collaborate to address this situation, targeting their efforts at educational,
      cultural, health policy and regulatory levels.

PMID- 23870414
TI  - Aggressiveness of end-of-life care for patients with colorectal cancer in
      Alberta, Canada: 2006-2009.
AB  - CONTEXT: North American studies have documented practice variations and
      deficiencies in end-of-life (EOL) cancer care, such as trends toward treating
      dying patients aggressively and disparities in access to palliative care or
      hospice services. OBJECTIVES: To assess the frequency of aggressive health care
      usage at the EOL and identify factors associated with receiving aggressive care
      among patients who died of colorectal cancer. METHODS: Data from the Alberta
      Cancer Registry, in/outpatient hospital records, and cancer electronic medical
      records were linked. Death in an acute care hospital, chemotherapy use in the
      last 14 days of life, more than one emergency room (ER) visit, more than one
      hospital admission, and any intensive care unit (ICU) admission in the last 30
      days of life were used as indicators of aggressive care. Logistic regression was
      used to identify risk factors associated with each indicator. RESULTS: A total of
      2074 patients were included: 50.1% died in an acute care hospital; 3.7% received
      chemotherapy in the last 14 days of life; and 12.5% had multiple ER visits, 9.5%
      had multiple hospitalizations, and 2.2% had an ICU admission during the last 30
      days of life. Age had the strongest association with chemotherapy use.
      Geographical region of residence had the strongest association with multiple ER
      visits and hospitalizations and dying in an acute care hospital. Tumor stage and
      duration of disease were associated with the ICU admission. CONCLUSION: The
      percentage of patients who died in an acute care hospital is higher than the 17%
      U.S. benchmark. Other indicators of receiving aggressive EOL care are consistent
      with existing care quality benchmarks. The considerable regional variation,
      however, indicates potential for system improvements.

PMID- 23870416
TI  - Translation of viral mRNAs that do not require eIF4E is blocked by the inhibitor
      4EGI-1.
AB  - High throughput screening has rendered new inhibitors of eukaryotic protein
      synthesis. One such molecule, 4EGI-1 has been reported to selectively block the
      initiation factor eIF4E. We have investigated the action of this inhibitor on
      translation directed by several viral mRNAs which, in principle, do not utilize
      eIF4E. We found that 4EGI-1 inhibits translation directed by poliovirus IRES, in
      rabbit reticulocyte lysates, to a similar extent as capped mRNA. Moreover, 4EGI-1
      inhibits translation driven by poliovirus IRES, both in vitro and in cultured
      cells, despite cleavage of eIF4G by picornavirus proteases. Finally, translation
      of vesicular stomatitis virus mRNAs and Sindbis virus subgenomic mRNA is blocked
      by 4EGI-1 in infected cells to a similar extent as cellular mRNAs. These findings
      cast doubt on the selective action of this inhibitor, and suggest that this
      molecule may affect other steps in protein synthesis unrelated to cap recognition
      by eIF4E. 

PMID- 23870415
TI  - Medical virology of hepatitis B: how it began and where we are now.
AB  - Infection with hepatitis B virus (HBV) may lead to acute or chronic hepatitis.
      HBV infections were previously much more frequent but there are still 240 million
      chronic HBV carriers today and ca. 620,000 die per year from the late sequelae
      liver cirrhosis or hepatocellular carcinoma. Hepatitis B was recognized as a
      disease in ancient times, but its etiologic agent was only recently identified.
      The first clue in unraveling this mystery was the discovery of an enigmatic serum
      protein named Australia antigen 50 years ago by Baruch Blumberg. Some years later
      this was recognized to be the HBV surface antigen (HBsAg). Detection of HBsAg
      allowed for the first time screening of inapparently infected blood donors for a
      dangerous pathogen. The need to diagnose clinically silent HBV infections was a
      strong driving force in the development of modern virus diagnostics. HBsAg was
      the first infection marker to be assayed with a highly sensitive radio immune
      assay. HBV itself was among the first viruses to be detected by assay of its DNA
      genome and IgM antibodies against the HBV core antigen were the first to be
      selectively detected by the anti-MU capture assay. The cloning and sequencing of
      the HBV genome in 1978 paved the way to understand the viral life cycle, and
      allowed development of efficient vaccines and drugs. Today's hepatitis B vaccine
      was the first vaccine produced by gene technology. Among the problems that still
      remain today are the inability to achieve a complete cure of chronic HBV
      infections, the recognition of occult HBV infections, their potential
      reactivation and the incomplete protection against escape mutants and
      heterologous HBV genotypes by HBV vaccines. 

PMID- 23870417
TI  - Frequency of C9orf72 repeat expansions in amyotrophic lateral sclerosis: a
      Belgian cohort study.
AB  - We determined the frequency of C9orf72 repeat expansions in a large cohort of
      Belgian patients with familial (fALS) and sporadic (sALS) amyotrophic lateral
      sclerosis (ALS). In total, 119 patients with fALS from 62 kindreds, 471 patients
      with sALS, and 384 control subjects were included. A C9orf72 repeat expansion was
      found in 32 of 62 fALS pedigrees (51.6%), in 45 of 471 patients with sALS (9.6%),
      but in none of the control subjects. Compared with fALS of unknown etiology or
      fALS caused by mutations in other ALS-causing genes, C9orf72 repeat expansion
      carriers had a later age at onset (57.3 vs. 51.4 years; p = 0.0061), a higher
      proportion of bulbar onset (31.9% vs. 12.5%, p < 0.0001), and a reduced survival
      (29.4 vs. 67.7 months, p = 0.0003). In the sALS cohort, there were no significant
      differences in these disease characteristics between the C9orf72 repeat expansion
      carriers and the noncarriers. C9orf72 repeat expansions are a frequent cause of
      ALS in Belgium, and also in sALS patients. These results might justify genetic
      testing of C9orf72 in all ALS patients. 

PMID- 23870418
TI  - Alzheimer's disease risk genes and the age-at-onset phenotype.
AB  - Despite the recent identification of several novel risk genes for Alzheimer's
      disease (AD), little is known about their influence on the age at onset (AAO) of
      AD. The AAO is a phenotype with a heritable component distinct from disease risk
      and may be a useful trait to study in the context of developing interventions for
      delaying the onset of AD. We studied the influence of 10 recently identified AD
      risk genes and APOE in relation to AAO in a large cohort of AD patients (N =
      2569). We find that the novel AD risk gene, PICALM, exerts a small effect on the
      AAO of AD with earlier disease onset in risk allele carriers. In addition, we
      confirmed the previously reported association between the APOE epsilon4 allele
      and earlier disease onset. None of the other AD risk genes influenced AAO of AD.
      Our results suggest that besides APOE, other genes associated with AD risk do not
      exert large effects on the AAO phenotype of AD.

PMID- 23870419
TI  - Effectiveness of cryotherapy for histologically confirmed cervical
      intraepithelial neoplasia grades 1 and 2 in an Indian setting.
AB  - OBJECTIVE: To describe the effectiveness of cryotherapy for treating women who
      were histologically confirmed to have cervical intraepithelial neoplasia (CIN) in
      India. METHODS: Data were analyzed retrospectively from screening projects that
      collected data from January 2001 to May 2008 in Trivandrum, India. Women with CIN
      were appropriately treated with cryotherapy by a trained nurse or physician and
      followed up for cure, adverse events, and complications. Cure was defined as
      absence of CIN during any follow-up visit at least 1 year after treatment.
      RESULTS: Among 236 women identified with CIN and appropriately treated with
      cryotherapy, 173 (81.6%) were followed up (158 CIN 1 and 15 CIN 2 cases). The
      percentage cure for CIN 1 and 2 lesions was 93.0% and 86.7% respectively. An odds
      ratio of 0.2 (95% confidence interval, 0.0-0.9) was observed for treatment
      received more than 2 months after screening as compared with treatment received
      within 2 months. Complications were observed in 1.2% of treated women and adverse
      events (discharge and mild pain) in 26.6%. CONCLUSION: The study affirms that
      trained mid-level providers can appropriately perform cryotherapy in primary
      healthcare services and that expanding such services in low-resource settings
      would increase the availability and accessibility of precancer treatment.

PMID- 23870420
TI  - Patient and provider attitudes toward genomic testing for prostate cancer
      susceptibility: a mixed method study.
AB  - BACKGROUND: The strong association between family history and prostate cancer
      (PCa) suggests a significant genetic contribution, yet specific highly penetrant
      PCa susceptibility genes have not been identified. Certain single-nucleotide
      polymorphisms have been found to correlate with PCa risk; however uncertainty
      remains regarding their clinical utility and how to best incorporate this
      information into clinical decision-making. Genetic testing is available directly
      to consumers and both patients and healthcare providers are becoming more aware
      of this technology. Purchasing online allows patients to bypass their healthcare
      provider yet patients may have difficulty interpreting test results and providers
      may be called upon to interpret results. Determining optimal ways to educate both
      patients and providers, and strategies for appropriately incorporating this
      information into clinical decision-making are needed. METHODS: A mixed-method
      study was conducted in Utah between October 2011 and December 2011. Eleven focus
      group discussions were held and surveys were administered to 23 first-degree
      relatives of PCa patients living in Utah and 24 primary-care physicians and
      urologists practicing in Utah to present specific information about these
      assessments and determine knowledge and attitudes regarding health implications
      of using these assessments. RESULTS: Data was independently coded by two
      researchers (relative Kappa = .88; provider Kappa = .77) and analyzed using a
      grounded theory approach. Results indicated differences in attitudes and
      behavioral intentions between patient and provider. Despite the test's
      limitations relatives indicated interest in genetic testing (52%) while most
      providers indicated they would not recommend the test for their patients (79%).
      Relatives expected providers to interpret genetic test results and use results to
      provide personalized healthcare recommendations while the majority of providers
      did not think the information would be useful in patient care (92%) and indicated
      low-levels of genetic self-efficacy. CONCLUSIONS: Although similarities exist,
      discordance between provider and patient attitudes may influence the effective
      translation of novel genomic tests into clinical practice suggesting both patient
      and provider perceptions and expectations be considered in development of
      clinical decision-support tools.

PMID- 23870422
TI  - Radiation sensitivity and sensitization in melanoma.

PMID- 23870424
TI  - Early brain computed tomography findings are associated with outcome in patients
      treated with therapeutic hypothermia after out-of-hospital cardiac arrest.
AB  - BACKGROUND: This study evaluated the association between the results of immediate
      brain computed tomography (CT) scans and outcome in patients who were treated
      with therapeutic hypothermia after cardiac arrest. The evaluation was based on
      the changes in the ratio of gray matter to white matter. METHODS: A total of 167
      patients who were successfully resuscitated after cardiac arrest from March 2009
      to December 2011 were included in this study. We selected 51 patients who
      received a brain CT scan within 1 hour after the return of spontaneous
      circulation (ROSC) and who had been treated with therapeutic hypothermia.
      Circular regions of measurement (10 mm2) were placed over regions of interest
      (ROIs), and the average attenuations in gray matter (GM) and white matter (WM)
      were recorded in the basal ganglia, at the level of the centrum semiovale and in
      the high convexity area. Three GM-to-WM ratios (GWRs) were calculated: one for
      the basal ganglia, one for the cerebrum and the average of the two. The
      neurological outcomes were assessed using the Cerebral Performance Category (CPC)
      scale at the time of hospital discharge, and a good neurological outcome was
      defined as a CPC score of 1 or 2. RESULTS: The average GWR was the strongest
      predictor of poor neurological outcome as determined using receiver operating
      characteristic curves (basal ganglia area under the curve (AUC) = 0.716; cerebrum
      AUC = 0.685; average AUC = 0.747). An average GWR < 1.14 predicted a poor
      neurological outcome with a sensitivity of 13.3% (95% confidence interval (CI)
      3.8-30.7), a specificity of 100% (95% CI 83.9-100), a positive predictive value
      of 100% (95% CI 2.5-100), and a negative predictive value of 44.7% (CI 28.9
      58.9). CONCLUSIONS: Our study demonstrated that low GWRs in the immediate brain
      CT scans of patients treated with therapeutic hypothermia after ROSC were
      associated with poor neurological outcomes. Immediate brain CT scans could help
      predict outcome after cardiac arrest.

PMID- 23870425
TI  - CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal
      studies.
AB  - BACKGROUND: Inflammatory markers are raised in cross-sectional studies of
      depressed patients and may represent an important mediating factor for behaviour,
      neural plasticity and brain structure. METHODS: We undertook a systematic review
      of longitudinal studies, investigating whether raised inflammatory markers
      indicate an increased risk of subsequent depressive symptoms. We searched three
      databases (1970-2012) for longitudinal studies with repeat data on CRP or IL-6
      levels and subsequent depressive symptoms. We calculated effect sizes using a
      mixed-effects model, with separate meta-analyses for inflammatory markers and age
      groups. RESULTS: We identified eight papers for CRP (14,832 participants) and
      three for IL-6 (3695 participants). There was a significant association between
      increased CRP and depressive symptoms (weighted-mean effect size 'unadjusted
      r'=0.069, p<0.0005; 'adjusted r'=0.046, p<0.0005), with moderate heterogeneity
      between studies (Q=11.21, p=0.08, I(2)=46.5). For IL-6 the weighted-mean effect
      size was smaller ('unadjusted r'=0.045, p-value=0.007; 'adjusted r'=0.097, p
      value=0.06). LIMITATIONS: The meta-analysis was based on a relatively small
      number of studies (particularly for IL-6) and only two inflammatory markers.
      There was moderate heterogeneity between studies and some evidence of publication
      bias. CONCLUSIONS: Raised inflammatory markers have a small but significant
      association with the subsequent development of depressive symptoms. This is a
      robust effect which remains significant after adjustment for age and a wide range
      of factors associated with risk for depression. Our results support the
      hypothesis that there is a causal pathway from inflammation to depression.

PMID- 23870423
TI  - Lifestyle factors and reproductive health: taking control of your fertility.
AB  - Approximately 10 to 15% of couples are impacted by infertility. Recently, the
      pivotal role that lifestyle factors play in the development of infertility has
      generated a considerable amount of interest. Lifestyle factors are the modifiable
      habits and ways of life that can greatly influence overall health and well-being,
      including fertility. Many lifestyle factors such as the age at which to start a
      family, nutrition, weight, exercise, psychological stress, environmental and
      occupational exposures, and others can have substantial effects on fertility;
      lifestyle factors such as cigarette smoking, illicit drug use, and alcohol and
      caffeine consumption can negatively influence fertility while others such as
      preventative care may be beneficial. The present literature review encompasses
      multiple lifestyle factors and places infertility in context for the couple by
      focusing on both males and females; it aims to identify the roles that lifestyle
      factors play in determining reproductive status. The growing interest and amount
      of research in this field have made it evident that lifestyle factors have a
      significant impact on fertility. 

PMID- 23870426
TI  - Higher cortisol levels at diurnal trough predict greater attentional bias towards
      threat in healthy young adults.
AB  - BACKGROUND: Attentional bias (AB), selective information processing towards
      threat, can exacerbate anxiety and depression. Despite growing interest,
      physiological determinants of AB are yet to be understood. We examined whether
      stress hormone cortisol and its diurnal variation pattern contribute to AB.
      METHODS: Eighty-seven healthy young adults underwent assessments for AB, anxious
      personality traits, depressive symptoms, and attentional function. Salivary
      cortisol was collected at three time points daily (at awakening, 30 min after
      awakening, and bedtime) for 2 consecutive days. We performed: (1) multiple
      regression analysis to examine the relationships between AB and the other
      measures and (2) analysis of variance (ANOVA) between groups with different
      cortisol variation patterns for the other measures. RESULTS: Multiple regression
      analysis revealed that higher cortisol levels at bedtime (p<0.001), an anxious
      personality trait (p=0.011), and years of education (p=0.036) were included in
      the optimal model to predict AB (adjusted R(2)=0.234, p<0.001). ANOVA further
      demonstrated significant mean differences in AB and depressive symptoms;
      individuals with blunted cortisol variation exhibited significantly greater AB
      and depression than those with moderate variation (p=0.037 and p=0.009,
      respectively). LIMITATIONS: Neuropsychological assessment focused on attention
      and cortisol measurement at three time points daily. CONCLUSIONS: We showed that
      higher cortisol levels at bedtime and blunted cortisol variation are associated
      with greater AB. Individuals who have higher cortisol levels at diurnal trough
      might be at risk of clinical anxiety or depression but could also derive more
      benefits from the attentional-bias-modification program.

PMID- 23870427
TI  - Psychotherapy for depression: a randomized clinical trial comparing schema
      therapy and cognitive behavior therapy.
AB  - BACKGROUND: The efficacy of Cognitive Behavior Therapy (CBT) for depression has
      been robustly supported, however, up to fifty percent of individuals do not
      respond fully. A growing body of research indicates Schema Therapy (ST) is an
      effective treatment for difficult and entrenched problems, and as such, may be an
      effective therapy for depression. METHODS: In this randomized clinical trial the
      comparative efficacy of CBT and ST for depression was examined. 100 participants
      with major depression received weekly cognitive behavioral therapy or schema
      therapy sessions for 6 months, followed by monthly therapy sessions for 6 months.
      Key outcomes were comparisons over the weekly and monthly sessions of therapy
      along with remission and recovery rates. Additional analyses examined outcome for
      those with chronic depression and comorbid personality disorders. RESULTS: ST was
      not significantly better (nor worse) than CBT for the treatment of depression.
      The therapies were of comparable efficacy on all key outcomes. There were no
      differential treatment effects for those with chronic depression or comorbid
      personality disorders. LIMITATIONS: This study needs replication. CONCLUSIONS:
      This preliminary research indicates that ST may provide an effective alternative
      therapy for depression.

PMID- 23870428
TI  - Lithium-associated hyperparathyroidism and hypercalcaemia: a case-control cross
      sectional study.
AB  - BACKGROUND: Lithium is recommended as a first-line treatment for Bipolar Disorder
      (BD). Thyroid and renal alterations are well known lithium side-effects, while
      effects on parathyroids are less studied. The aim of this case-control cross
      sectional study is to compare parathyroid hormone (PTH) and calcium levels in
      lithium-exposed bipolar patients and in subjects who had never been exposed to
      lithium. METHODS: 112 BD patients were enrolled, 58 on lithium since at least 1
      month (mean exposure 60.8 +/- 74.8 months) and 54 in the control group. Blood
      exams included complete blood count, PTH, total and ionized calcium, TSH, T3 and
      T4, creatinine, urea, sodium and potassium, and lithium serum levels. The
      Student's t-test and the Pearson's Chi-square test were used for bivariate
      analyses. A linear regression model was used to analyze the relationship between
      the duration of exposure to lithium and PTH and calcium levels. RESULTS: PTH and
      ionized calcium levels were significantly higher in lithium-exposed patients; the
      proportions of subjects with hyperparathyroidism (8.6%) and hypercalcaemia
      (24.1%) were significantly greater in lithium-exposed patients. The linear
      regression analyses showed a significant effect of exposure to lithium in months
      on ionized calcium levels but not on PTH levels. LIMITATIONS: Given the cross
      sectional design of the study we could not identify the exact time of occurrence
      of hyperparathyroidism. CONCLUSIONS: Our results indicate that lithium-associated
      stimulation of parathyroid function is more common than assumed to date. Among
      parameters to be evaluated prior to lithium implementation and during long-term
      lithium maintenance, calcium (and eventually PTH) should be added.

PMID- 23870429
TI  - Using photos to develop text messages to promote walking.
AB  - PURPOSE: Sending text messages (TMs) is a promising global intervention to help
      adults increase their engagement in walking as a form of physical activity (PA).
      But, little is known about how effective and acceptable TMs are developed.
      DESIGN: Our study was designed to (a) determine the acceptability, among low
      income adults, of receiving TMs to increase their walking and (b) develop, using
      photos to prompt discussion, a participant-generated database of TMs to promote
      walking. METHODS: In 2011, three focus groups (low-income, sedentary adults) met
      at community clinics (one focus group at each of three clinics). To promote
      dialogue to help develop TMs, we created a discussion guide and a set of 40
      photos depicting barriers to increasing PA or showing people walking. A content
      analysis of TMs developed was done using audiotaped transcripts, photo page
      notes, flip chart notes, and field notes. FINDINGS: Twelve TM themes emerged,
      including 172 TMs developed by the 23 study participants (age 50 +/- 6.3 years).
      CONCLUSIONS: Using TMs to help achieve walking goals is an acceptable method of
      promoting PA with adults. Using culturally relevant photos to prompt discussion,
      focus groups can develop a database of PA-related TMs to promote walking.
      CLINICAL RELEVANCE: Physical inactivity is a significant contributor to adult
      health problems worldwide, and walking is a realistic method of increasing PA.
      Using focus groups and photos, individuals can generate acceptable, personalized
      and innovative TMs to promote walking.

PMID- 23870430
TI  - 2-Amino-[1,2,4]triazolo[1,5-a]pyridines as JAK2 inhibitors.
AB  - The advancement of a series of ligand efficient 2-amino-[1,2,4]triazolo[1,5
      a]pyridines, initially identified from high-throughput screening, to a JAK2
      inhibitor with pharmacodynamic activity in a mouse xenograft model is disclosed. 

PMID- 23870432
TI  - Pesticide contamination and phytotoxicity of sediment interstitial water to
      tropical benthic microalgae.
AB  - Many organic compounds including some herbicides concentrate in sediment, thus it
      may be expected that interstitial waters contain higher concentrations of these
      contaminants than the water column. To estimate benthic microalgal exposure to
      pesticides, sediment and interstitial water sampled in the dry season from four
      major rivers in north Queensland, Australia, were analysed for these
      contaminants. Interstitial water extracts from the sediments were tested for
      acute phytotoxicity to benthic microalgae using PAM fluorometry and the results
      were compared with chemical analyses of the same water samples. A range of
      pesticides were detected in both sediment and interstitial waters from all sites,
      notably the herbicide diuron at concentrations ranging from 0.3 to 11 MUg kg(-1)
      dry weight sediment, and up to 68 ng L(-1) in interstitial waters. Herbicide
      concentrations estimated from partition coefficients and the sediment
      concentrations typically overestimated analytically determined concentrations
      present in interstitial water by an order of magnitude. The analytically
      determined herbicide concentrations in the interstitial water explained most of
      the phytotoxicity measured with the bioassay; however, photoinhibition was
      slightly higher than expected based on analytical results, indicating the
      presence of unidentified phytotoxins. These results demonstrate the presence of
      pesticides in interstitial waters in the Tropical dry season, sometimes at
      concentrations that may affect sensitive benthic organisms, and supports the use
      of the I-PAM bioassay as a valuable tool in exposure- and environmental risk- and
      impact-assessments.

PMID- 23870431
TI  - Different Sarcocystis spp. are present in bovine eosinophilic myositis.
AB  - It has been suggested that Sarcocystis species are associated with bovine
      eosinophilic myositis (BEM). To date, parasite identification in this myopathy
      has been based on morphological techniques. The aim of the present study was to
      use molecular techniques to identify Sarcocystis species inside lesions of BEM.
      Histologically, BEM lesions of 97 condemned carcasses were examined for the
      presence of Sarcocystis species. Intralesional and extralesional cysts were
      collected using laser capture microdissection and the species was determined with
      a PCR-based technique based on 18S rDNA. Intralesional sarcocysts or remnants
      were found in BEM lesions in 28% of the carcasses. The majority (82%) of
      intralesional Sarcocystis species were found to be S. hominis. However S. cruzi
      and S. hirsuta were also found, as well as an unidentified species. It can be
      concluded that Sarcocystis species present in lesions of BEM are not restricted
      to one species. 

PMID- 23870433
TI  - Proxy model materials to simulate the elastic properties of digested municipal
      sludge.
AB  - The elastic rheological properties of sludge are complex and evolve with time as
      a result of ageing and microbial activity. Due to the peculiar nature of sludge,
      this makes the measurement of physical parameters difficul. The challenge is to
      identify a reference material that can be used as a proxy for industrial process
      design or optimization. In this study, respectively the mixtures of 0.5%, 0.7%
      and 1% glass beads suspension in water have been added to 0.5%, 0.7% and 1%
      carbopol dissolved in water and neutralized with NaOH to prepare gel, at
      different ratios. Elastic and loss moduli have been determined for different
      glass bead suspension ratios in the range of 0%-80%. The results showed that
      there is a critical glass bead suspension/carbopol ratio at which the elastic
      properties of the mixture changes dramatically. The elastic properties of these
      model mixtures of different glass bead/carbopol ratio suspensions are compared
      with the elastic property of municipal sludge sampled from a Melbourne Waste
      Water Treatment Plant, and similarity established.

PMID- 23870434
TI  - Evaluation of trace metals bioavailability in Japanese river waters using DGT and
      a chemical equilibrium model.
AB  - To develop efficient and effective methods of assessing and managing the risk
      posed by metals to aquatic life, it is important to determine the effects of
      water chemistry on the bioavailability of metals in surface water. In this study,
      we employed the diffusive gradients in thin-films (DGT) to determine the
      bioavailability of metals (Ni, Cu, Zn, and Pb) in Japanese water systems. The DGT
      results were compared with a chemical equilibrium model (WHAM 7.0) calculation to
      examine its robustness and utility to predict dynamic metal speciation. The DGT
      measurements showed that biologically available fractions of metals in the rivers
      impacted by mine drainage and metal industries were relatively high compared with
      those in urban rivers. Comparison between the DGT results and the model
      calculation indicated good agreement for Zn. The model calculation concentrations
      for Ni and Cu were higher than the DGT concentrations at most sites. As for Pb,
      the model calculation depended on whether the precipitated iron(III) hydroxide or
      precipitated aluminum(III) hydroxide was assumed to have an active surface. Our
      results suggest that the use of WHAM 7.0 combined with the DGT method can predict
      bioavailable concentrations of most metals (except for Pb) with reasonable
      accuracy. 

PMID- 23870435
TI  - Millimeter-scale alkalinity measurement in marine sediment using DET probes and
      colorimetric determination.
AB  - Constrained DET (Diffusive Equilibration in Thin films) probes equipped with 75
      sampling layers of agarose gel (DGT Research((c))) were used to sample bottom and
      pore waters in marine sediment with a 2 mm vertical resolution. After retrieval,
      each piece of hydrogel, corresponding to 25 MUL, was introduced into 1 mL of
      colorimetric reagent (CR) solution consisting of formic acid and bromophenol
      blue. After the elution/reaction time, absorbance of the latter mixture was read
      at 590 nm and compared to a calibration curve obtained with the same protocol
      applied to mini DET probes soaked in sodium hydrogen carbonate standard
      solutions. This method allows rapid alkalinity determinations for the small
      volumes of anoxic pore water entrapped into the gel. The method was assessed on
      organic-rich coastal marine sediments from Thau lagoon (France). Alkalinity
      values in the overlying waters were in agreement with data obtained by classical
      sampling techniques. Pore water data showed a progressive increase of alkalinity
      in the sediment from 2 to 10 mmol kg(-1), corresponding to anaerobic respiration
      in organic-rich sediments. Moreover, replicates of high-resolution DET profiles
      showed important lateral heterogeneity at a decimeter scale. This underlines the
      importance of high-resolution spatial methods for alkalinity profiling in coastal
      marine systems.

PMID- 23870436
TI  - Temperature-induced impacts on groundwater quality and arsenic mobility in anoxic
      aquifer sediments used for both drinking water and shallow geothermal energy
      production.
AB  - Aquifers used for the production of drinking water are increasingly being used
      for the generation of shallow geothermal energy. This causes temperature
      perturbations far beyond the natural variations in aquifers and the effects of
      these temperature variations on groundwater quality, in particular trace
      elements, have not been investigated. Here, we report the results of column
      experiments to assess the impacts of temperature variations (5 degrees C, 11
      degrees C, 25 degrees C and 60 degrees C) on groundwater quality in anoxic
      reactive unconsolidated sandy sediments derived from an aquifer system widely
      used for drinking water production in the Netherlands. Our results showed that at
      5  degrees C no effects on water quality were observed compared to the reference
      of 11 degrees C (in situ temperature). At 25 degrees C, As concentrations were
      significantly increased and at 60  degrees C, significant increases were observed
      pH and DOC, P, K, Si, As, Mo, V, B, and F concentrations. These elements should
      therefore be considered for water quality monitoring programs of shallow
      geothermal energy projects. No consistent temperature effects were observed on
      Na, Ca, Mg, Sr, Fe, Mn, Al, Ba, Co, Cu, Ni, Pb, Zn, Eu, Ho, Sb, Sc, Yb, Ga, La,
      and Th concentrations, all of which were present in the sediment. The temperature
      induced chemical effects were probably caused by (incongruent) dissolution of
      silicate minerals (K and Si), desorption from, and potentially reductive
      dissolution of, iron oxides (As, B, Mo, V, and possibly P and DOC), and
      mineralisation of sedimentary organic matter (DOC and P).

PMID- 23870437
TI  - Engineering lentiviral vectors for modulation of dendritic cell apoptotic
      pathways.
AB  - BACKGROUND: Dendritic cells (DCs) are promising mediators of anti-tumor immune
      responses due to their potent antigen-presentation capacity. Unfortunately,
      cancer cells can often disarm differentiated DCs by rendering them incapable of
      maturation or by promoting their apoptosis. DC vaccine regimens attempt to
      generate functional DCs and preload them with Tumor-Associated Antigens (TAAs) to
      target various malignancies. Despite these efforts, the efficacy of DC vaccines
      in clinical trials is still rather disappointing to date. In addition to
      undergoing cancer-induced apoptosis, it is well established that DCs are
      intrinsically short-lived cell types. It is likely that a significant portion of
      infused DCs undergo apoptosis prior to locating and activating naive TAA-reactive
      T cells. METHODS: In our current study, we constructed and investigated novel
      bicistronic lentivectors (LVs) encoding the cDNA for the xeno-TAA, rat HER-2/neu
      (rHER-2), along with five candidate mouse DC survival factors (c-FLIPS, c-FLIPL,
      Bcl-XL, M11L, and AKT-1) that operate in both the extrinsic and intrinsic cycles
      of apoptosis. The murine DC cell line, DC2.4 was transduced separately with each
      novel LV construct. Infected cells were enriched via flow cytometric methods
      based on rHER-2 expression. Transduced DC2.4 cell lines were then exposed to
      Fetal Calf Serum (FCS) withdrawal and to specific pharmacological apoptosis
      inducing agents. DC2.4 cell death was assayed based on Annexin V and PI double
      positive staining via flow cytometry. The phenotype and function of transduced
      DC2.4 cells and primary bone marrow-derived DCs were then assessed via expression
      and secretion of DC markers and cytokines, respectively. RESULTS: DC2.4 cells
      transduced with LVs encoding cDNAs for c-FLIPS, c-FLIPL, Bcl-XL, and M11L were
      protected from apoptosis when exposed to low FCS-containing culture media. When
      treated with an anti-CD95 antibody, only DC2.4 cells transduced with LVs encoding
      c-FLIPS and c-FLIPL were protected from apoptosis. In contrast, only DC2.4 cells
      transduced with LVs encoding Bcl-XL and M11L were protected from effects of
      staurosporine (STS) treatment. Also, LV-modified DCs maintained their original
      phenotype and function. CONCLUSIONS: We present evidence that by employing novel
      recombinant bicistronic LVs we can simultaneously load DCs with a relevant TAA
      and block apoptosis; thereby confirming the usage of such LVs in the modulation
      of DC lifespan and function.

PMID- 23870438
TI  - Incidence of and risk factors for vitreous loss in resident-performed
      phacoemulsification surgery.
AB  - PURPOSE: To determine the incidence of and risk factors for posterior capsule
      rupture and vitreous loss during phacoemulsification performed by ophthalmology
      residents. SETTING: Academic ophthalmology resident training center, Tehran,
      Iran. DESIGN: Cross-sectional study. METHODS: This study included patients who
      had phacoemulsification by ophthalmology residents from August 2010 to August
      2011. The complications occurring during surgery and the rate of vitreous loss
      and posterior capsule rupture were studied. RESULTS: Five hundred eyes of 500
      patients, including 255 (51%) men and 245 (49%) women with a mean age of 67 years
      +/- 10 (SD) (range 27 to 105 years), were studied. Fifty-one eyes (10.2%)
      developed vitreous loss, and 48 eyes (9.6%) developed posterior capsule rupture
      and vitreous loss. On univariate analysis, significant risk factors for vitreous
      loss included diabetes mellitus (P=.001), shallow anterior chamber (P=.01),
      absence of supervision by a faculty member (P=.007), larger capsulorhexis
      (P=.02), anterior capsule tear (P=.001), and longer effective phacoemulsification
      time (EPT) (P=.003). Multivariate data analysis using stepwise logistic
      regression analysis showed anterior capsule tear (odds ratio [OR], 2.63; 95%
      confidence interval [CI], 1.09-6.29), longer EPT (OR, 1.01; 95% CI, 1.003-1.02),
      and lack of supervision by attending physicians (OR, 4.28; 95% CI, 1.44-12.67) to
      be significant independent risk factors associated with vitreous loss.
      CONCLUSION: Direct attending supervision and careful case selection for the level
      of cataract surgery residency are of utmost importance in avoiding sight
      threatening complications.

PMID- 23870439
TI  - Black-on-black secondary occlusive IOL implantation to alleviate enigmatic light
      perception through a black IOL.
AB  - A 61-year-old woman presented with an 18-year history of a debilitating ghosting
      phenomenon and light perception in her right eye following implantation of a
      Morcher black intraocular lens (IOL) for intractable diplopia. On 5 occasions,
      she was referred to hospital ophthalmology, repeatedly requesting right optic
      nerve transection to alleviate the symptoms. The mechanism of light perception
      across the occlusive IOL remained enigmatic, preventing appropriate management.
      Morcher occlusive IOLs transmit high levels of near infrared (IR) light, which
      may cause light perception under photopic conditions by long-wavelength cone
      photoreceptors. Considering this, we implanted a near IR-blocking Artisan black
      iris-claw IOL anterior to the Morcher occlusive IOL. Postoperatively, the light
      perception and ghosting disappeared and the visual quality of life score (VF-14)
      increased from 41 to 86. We suggest consideration of this surgical approach of
      black-on-black IOL implantation for patients with refractory light perception
      despite implantation of a near IR-transmitting occlusive IOL. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 23870440
TI  - The influence of fidelity of implementation on teacher-student interaction
      quality in the context of a randomized controlled trial of the Responsive
      Classroom approach.
AB  - This study examined the direct and indirect effects between training in the
      Responsive Classroom(r) (RC) approach, teachers' uptake of RC practices, and
      teacher-student interaction quality, using a structural equation modeling
      framework. A total of 24 schools were randomly assigned to experimental or
      control conditions. Third- and fourth-grade teachers in treatment schools (n=132)
      received training in the RC approach, whereas teachers in control schools (n=107)
      continued "business as usual." Observers rated teachers' fidelity of
      implementation (FOI) of RC practices 5 times throughout the year using the
      Classroom Practices Observation Measure. In addition, teachers completed self
      report measures of FOI, the Classroom Practices Teacher Survey and Classroom
      Practices Frequency Survey, at the end of the school year. Teacher-student
      interactions were rated during classroom observations using the Classroom
      Assessment Scoring System. Controlling for teachers' grade level and teacher
      student interaction quality at pretest, RC training was expected to predict
      posttest teacher-student interaction quality directly and indirectly through FOI.
      Results supported only a significant indirect effect, beta=0.85, p=.002.
      Specifically, RC teachers had higher levels of FOI of RC practices, beta=1.62,
      p<.001, R2=.69. In turn, FOI related to greater improvement in teacher-student
      interaction quality, beta=0.52, p=.001, R2=.32. Discussion highlights factors
      contributing to variability in FOI and school administrators roles in supporting
      FOI.

PMID- 23870443
TI  - The impact of instructional context on classroom on-task behavior: a matched
      comparison of children with ADHD and non-ADHD classmates.
AB  - Classroom inattentiveness is an important reason for clinical referral of
      children with ADHD and a strong predictor of their educational achievement. This
      study investigates classroom on-task behavior of Flemish children with ADHD
      withdrawn from medication as a function of instructional context. Thirty-one
      pairs of children (one with ADHD and one age- and sex-matched control; 25 boys
      and 6 girls 6 to 12years of age) were observed in their classroom environment
      during two consecutive school days. On-task behavior (time on-task and on-task
      span) of ADHD and non-ADHD individuals was compared in different class contexts
      (i.e., different class structures and academic content types). Individualized
      teacher supervision was simultaneously assessed. Generalized estimation equation
      analyses showed that children with ADHD were significantly less on-task than
      controls during individual work and whole class group teaching, but not during
      small group work, and had significantly shorter on-task span during academic
      tasks (mathematics, language, and sciences) and instructional transitions between
      tasks, but not during music and arts. These effects persisted even after
      controlling for the higher levels of teacher supervision observed for ADHD pupils
      (7%) across all contexts (vs. 4% in controls). Findings suggest that despite
      receiving more overall teacher supervision, children with ADHD displayed lower
      levels of on-task behavior in settings that place high self-regulatory,
      information processing, and motivational demands on them. This finding may have
      initial implications for classroom interventions in this population. 

PMID- 23870442
TI  - Examining the link between forms of bullying behaviors and perceptions of safety
      and belonging among secondary school students.
AB  - Research suggests that students who bully may perceive the school climate less
      favorably. Person-centered analyses were used to identify distinct groupings of
      bullying behaviors and related social-emotional factors (i.e., victimization,
      internalizing, and perception of school and bullying climate). Latent class
      analyses were conducted on a sample of 10,254 middle and 2509 high school
      students and indicated four classes in middle school (Low Involvement, Verbal,
      High Physical/High Verbal, and High Involvement) and three classes in high school
      (Low Involvement, Verbal, and High Involvement). A Low Involvement bullying class
      characterized most students and was related to positive adjustment, whereas a
      High Involvement bullying class represented the smallest proportion of the sample
      (1.6% middle school and 7.3% in high school). Students in the High Involvement
      class reported increased victimization and internalizing problems, feeling less
      safe and less belonging, and perceiving the school climate to be more supportive
      of bullying (i.e., perceiving adults' prevention and intervention efforts as
      ineffective). In middle school, the High Physical/High Verbal class reported
      significantly higher levels of victimization as compared to the Verbal class.
      Findings highlight heterogeneity in bullying behaviors and underscore the
      importance of prevention and intervention programming that addresses safety and
      belonging. 

PMID- 23870441
TI  - Opening the "Black Box": family check-up intervention effects on self-regulation
      that prevents growth in problem behavior and substance use.
AB  - Family-school interventions are a well-established method for preventing and
      remediating behavior problems in at-risk youth, yet the mechanisms of change
      underlying their effectiveness are often overlooked or poorly understood. The
      Family Check-Up (FCU), a school-based, family-centered intervention, has been
      consistently associated with reductions in youth antisocial behavior, deviant
      peer group affiliation, and substance use. The purpose of this study was to
      explore proximal changes in student-level behavior that accounts for links
      between implementation of the FCU and changes in youth problem behavior. Data
      were drawn from a randomized controlled trial study of the efficacy of the FCU
      among 593 ethnically diverse middle school students followed longitudinally from
      6th through 8th grades. Latent growth curve analyses revealed that random
      assignment to the FCU intervention condition was related to increased mean levels
      of students' self-regulation from 6th to 7th grades, which in turn reduced the
      risk for growth in antisocial behavior, involvement with deviant peers, and
      alcohol, tobacco, and marijuana use through the 8th grade. Overall, these
      findings highlight the robust implications of self-regulation as a proximal
      target for family-centered interventions. 

PMID- 23870444
TI  - Predictive validity of curriculum-based measurement and teacher ratings of
      academic achievement.
AB  - Two alternative universal screening approaches to identify students with early
      learning difficulties were examined, along with a combination of these
      approaches. These approaches, consisting of (a) curriculum-based measurement
      (CBM) and (b) teacher ratings using Performance Screening Guides (PSGs), served
      as predictors of achievement tests in reading and mathematics. Participants
      included 413 students in grades 1, 2, and 3 in Tennessee (n=118) and Wisconsin
      (n=295) who were divided into six subsamples defined by grade and state. Reading
      and mathematics achievement tests with established psychometric properties were
      used as criteria within a concurrent and predictive validity framework. Across
      both achievement areas, CBM probes shared more variance with criterion measures
      than did teacher ratings, although teacher ratings added incremental validity
      among most subsamples. PSGs tended to be more accurate for identifying students
      in need of assistance at a 1-month interval, whereas CBM probes were more
      accurate at a 6-month interval. Teachers indicated that (a) false negatives are
      more problematic than are false positives, (b) both screening methods are useful
      for identifying early learning difficulties, and (c) both screening methods are
      useful for identifying students in need of interventions. Collectively, these
      findings suggest that the two types of measures, when used together, yield
      valuable information about students who need assistance in reading and
      mathematics. 

PMID- 23870445
TI  - Student-teacher relationship quality and academic adjustment in upper elementary
      school: the role of student personality.
AB  - This study tested a theoretical model considering students' personality traits as
      predictors of student-teacher relationship quality (closeness, conflict, and
      dependency), the effects of student-teacher relationship quality on students'
      math and reading achievement, and the mediating role of students' motivational
      beliefs on the association between student-teacher relationship quality and
      achievement in upper elementary school. Surveys and tests were conducted among a
      nationally representative Dutch sample of 8545 sixth-grade students and their
      teachers in 395 schools. Structural equation models were used to test direct and
      indirect effects. Support was found for a model that identified conscientiousness
      and agreeableness as predictors of close, nonconflictual relationships, and
      neuroticism as a predictor of dependent and conflictual relationships.
      Extraversion was associated with higher levels of closeness and conflict, and
      autonomy was only associated with lower levels of dependency. Students'
      motivational beliefs mediated the effects of dependency and student-reported
      closeness on reading and math achievement. 

PMID- 23870446
TI  - A cross-battery, reference variable, confirmatory factor analytic investigation
      of the CHC taxonomy.
AB  - The Cattell-Horn-Carroll (CHC) taxonomy has been used to classify and describe
      human cognitive abilities. The ability factors derived from the CHC taxonomy are
      often assumed to be invariant across multiple populations and intelligence
      batteries, which is an important assumption for research and assessment. In this
      study, data from five different test batteries that were collected during
      separate Kaufman Assessment Battery for Children-Second Edition (KABC-II; Kaufman
      & Kaufman, 2004) concurrent validity studies were factor-analyzed jointly.
      Because the KABC-II was administered to everyone in the validity studies, it was
      used as a reference battery to link the separate test batteries in a "cross
      battery" confirmatory factor analysis. Some findings from this analysis were that
      CHC-based test classifications based on theory and prior research were
      straightforward and accurate, a first-order Fluid/Novel Reasoning (Gf) factor was
      equivalent to a second-order g factor, and sample heterogeneity related to SES
      and sex influenced factor loadings. It was also shown that a reference variable
      approach, used in studies that incorporate planned missingness into data
      collection, may be used successfully to analyze data from several test batteries
      and studies. One implication from these findings is that CHC theory should
      continue to serve as a useful guide that can be used for intelligence research,
      assessment, and test development. 

PMID- 23870448
TI  - Cancer patients' and professional caregivers' needs, preferences and factors
      associated with receiving and providing fertility-related information: a mixed
      methods systematic review.
AB  - OBJECTIVES: Cancer treatment can impair fertility. The aim of this review was to
      investigate (1) fertility information needs, receipt and provision, (2) fertility
      information preferences, and (3) factors associated with receiving/providing
      fertility information. Cancer patients' and professional caregivers' perspectives
      were considered. DESIGN: Mixed-methods systematic review. DATA SOURCES: Six
      electronic databases (PubMed, Web of Science, CINAHL, CRD, Embase) were
      systematically screened to retrieve articles published between January 2001 and
      March 2012. Reference lists and conference abstracts were checked for additional
      publications. REVIEW METHODS: The principles outlined in the Cochrane Handbook
      for Systematic Reviews of Intervention were applied. Publications were included
      if they explored fertility-related information/communication in cancer
      patients/survivors of reproductive age or professional caregivers. The Critical
      Appraisal Skills Programme for Qualitative Studies and the Quality Assessment
      Tool for Quantitative Studies were used to assess the methodological quality. A
      standardised form based on the Cochrane guidelines for systematic reviews was
      used to extract the data. Two independent reviewers performed all methodological
      steps. RESULTS: Of the 1872 papers found, 27 were included in this review. The
      majority (66-100%) of the cancer patients wanted information about the impact of
      cancer therapy on fertility. The need and importance were higher in younger and
      childless patients, and in patients having childbearing plans. The number of
      patients receiving this information ranged from 0% to 85%. Several factors were
      associated with the lack of information receipt, including female gender and age
      35 years or older. Patients preferred information via an individual consultation.
      In the diagnostic phase patients needed information about the impact of the
      treatment on fertility and preservation options. At the end or after the
      treatment, information needs shifted towards long term effects. Professional
      caregivers experienced several barriers in providing fertility information,
      including caregiver-, patient- and institutional-related factors. Nurses in
      particular, perceived difficulty in providing fertility-related information due
      to additional barriers associated with limited responsibility and opportunity in
      fertility information provision. CONCLUSION: Professional caregivers experienced
      multiple barriers that hinder information provision. Further exploration of the
      role of Advanced Nurse Practitioners/Midwifes and the development of an evidence
      based intervention to overcome caregiver-related barriers are recommended to
      improve information provision.

PMID- 23870449
TI  - Pediatric non alcoholic fatty liver disease: more on novel treatment targets.
AB  - The mainstay treatment of non alcoholic fatty liver disease (NAFLD) based on
      weight loss and/or lifestyle changes is most often unsuccessful at all ages, thus
      requiring the implementation of pharmacological strategies. Targeting insulin
      resistance and oxidative stress has recently proven unsatisfactory. Among a
      number of proposed innovative approaches targeting novel pathomechanisms,
      probiotics appear an interesting and reasonable option acting on gut-liver axis
      malfunction through the modulation of diet-driven, obesogenic, and inflammatory
      intestinal microbiota.A combined multiple pharmacological therapy directed
      simultaneously towards novel and old pathomechanisms (including, e.g., insulin
      resistance, oxidative stress, gut-liver axis, apoptosis) along with lifestyle
      interventions however might be necessary both in adult and pediatric NAFLD
      therapy. 

PMID- 23870447
TI  - Effects of a cognitive training on spatial learning and associated functional
      brain activations.
AB  - BACKGROUND: Both cognitive and physical exercise have been discussed as promising
      interventions for healthy cognitive aging. The present study assessed the effects
      of cognitive training (spatial vs. perceptual training) and physical training
      (endurance training vs. non-endurance training) on spatial learning and
      associated brain activation in 33 adults (40-55 years). Spatial learning was
      assessed with a virtual maze task, and at the same time neural correlates were
      measured with functional magnetic resonance imaging (fMRI). RESULTS: Only the
      spatial training improved performance in the maze task. These behavioral gains
      were accompanied by a decrease in frontal and temporal lobe activity. At
      posttest, participants of the spatial training group showed lower activity than
      participants of the perceptual training group in a network of brain regions
      associated with spatial learning, including the hippocampus and parahippocampal
      gyrus. No significant differences were observed between the two physical
      intervention groups. CONCLUSIONS: Functional changes in neural systems associated
      with spatial navigation can be induced by cognitive interventions and seem to be
      stronger than effects of physical exercise in middle-aged adults.

PMID- 23870450
TI  - Effect of private insurance incentive policy reforms on trends in coronary
      revascularisation procedures in the private and public health sectors in Western
      Australia: a cohort study.
AB  - BACKGROUND: The Australian federal government introduced private health insurance
      incentive policy reforms in 2000 that increased the uptake of private health
      insurance in Australia. There is currently a lack of evidence on the effect of
      the policy reforms on access to cardiovascular interventions in public and
      private hospitals in Australia. The aim was to investigate whether the increased
      private health insurance uptake influenced trends in emergency and elective
      coronary artery revascularisation procedures (CARPs) for private and public
      patients. METHODS: We included 34,423 incident CARPs from Western Australia
      during 1995-2008 in this study. Rates of emergency and elective CARPs were
      stratified for publicly and privately funded patients. The average annual percent
      change (AAPC) in trend was calculated before and after 2000 using joinpoint
      regression. RESULTS: The rate of emergency CARPs, which were predominantly
      percutaneous coronary interventions (PCIs) with stenting, increased throughout
      the study period for both public and private patients (AAPC=12.9%, 95%
      CI=5.0,22.0 and 14.1%, 95% CI=9.8,18.6, respectively) with no significant
      difference in trends before and after policy implementation. The rate of elective
      PCIs with stenting from 2000 onwards remained relatively stable for public
      patients (AAPC=-6.0, 95% C= -16.9,6.4), but increased by 4.1% on average annually
      (95% CI=1.8,6.3) for private patients (pdifference=0.04 between groups). This
      rate increase for private patients was only seen in people aged over 65 years and
      people residing in high socioeconomic areas. CONCLUSIONS: The private health
      insurance incentive policy reforms are a likely contributing factor in the shift
      in 2000 from public to privately-funded elective PCIs with stenting. These
      reforms as well as the increasing number of private hospitals may have been
      successful in increasing the availability of publicly-funded beds since 2000.

PMID- 23870451
TI  - Learning experiences of oral hygiene students in the clinical environment.
AB  - OBJECTIVES: To determine how students used daily and term-based clinical
      assessment tools, students' experience of clinical teaching and clinical
      assessment. METHODS: This was a descriptive, cross-sectional study. The study
      population included final-year Degree in Oral Health (BOH) students (n = 34).
      Data were collected by means of a self-administered questionnaire using open- and
      closed-ended questions. RESULTS: The response rate was 85% (n = 29). Respondents
      reported that term-based assessment tools were more useful than daily assessment
      tools in preparing for clinical sessions, in guiding their patient management and
      as a reflection of their competence. Factors influencing student experiences
      include authentic learning opportunities such as performing a variety of
      procedures, patient appreciation and positive reinforcement from supervisors;
      consistent and appropriate feedback on their performance, feedback in the
      presence of a patient; supervisor qualities of being patient, respectful, non
      threatening and being positive role models; and organizational aspects such as
      punctuality and availability of supervisors. Inconsistencies were found in
      student experiences in terms of the quality of feedback received. Assessment
      experiences include inconsistency between supervisors and not being informed of
      assessment scores. Regular verbal feedback or being appraised of their assessment
      scores was reported more frequently for term-based assessment (77%) than for
      daily assessment (27%). CONCLUSION: The results of this study suggest that a
      blueprint defining assessment as a means to drive student learning is inadequate.
      A more comprehensive approach encompassing all the parameters that impact the
      learning process may be more useful.

PMID- 23870452
TI  - Tea and coffee scalds in children: a British epidemic requiring a solution.

PMID- 23870453
TI  - Pharmacological and toxicological evaluation of Sulcona((r)), a traditional
      Siddha medicine used in the treatment of burns.
AB  - Sulcona, a Siddha proprietary medicine used for the treatment of burns, has been
      in practice for more than 50 years. This medicine has been successfully used on
      several burned patients with an excellent recovery and safety record. In this
      manuscript, we investigate some of its pharmacological and safety profiles.
      Treatment of cells with Sulcona induced a statistically significant increase in
      population doubling compared to concurrent controls in proliferating human
      lymphocytes as well as in Balb/c 3T3 cells, suggesting that it stimulates cell
      proliferation. Sulcona exhibited some antibacterial activity against Pseudomonas
      aeruginosa, Salmonella typhi and Staphylococcus aureus. Carrageenan-induced rat
      paw edema testing suggested that Sulcona has some anti-inflammatory properties.
      Patch testing showed that Sulcona has mild anesthetic effects. The above
      properties suggest Sulcona's pharmacological properties aidin treatment of burns.
      Sulcona did not show any skin irritation or sensitization or mutagenic potential
      suggesting that it is safe for use. Further work is necessary to elucidate its
      exact mechanisms of action. 

PMID- 23870454
TI  - Developing the national community health assistant strategy in Zambia: a policy
      analysis.
AB  - BACKGROUND: In 2010, the Ministry of Health in Zambia developed the National
      Community Health Assistant strategy, aiming to integrate community health workers
      (CHWs) into national health plans by creating a new group of workers, called
      community health assistants (CHAs). The aim of the paper is to analyse the CHA
      policy development process and the factors that influenced its evolution and
      content. A policy analysis approach was used to analyse the policy reform
      process. METHODOLOGY: Data were gathered through review of documents, participant
      observation and key informant interviews with CHA strategic team members in
      Lusaka district, and senior officials at the district level in Kapiri Mposhi
      district where some CHAs have been deployed. RESULTS: The strategy was developed
      in order to address the human resources for health shortage and the challenges
      facing the community-based health workforce in Zambia. However, some actors
      within the strategic team were more influential than others in informing the
      policy agenda, determining the process, and shaping the content. These actors
      negotiated with professional/statutory bodies and health unions on the need to
      develop the new cadre which resulted in compromises that enabled the policy
      process to move forward. International agencies also indirectly influenced the
      course as well as the content of the strategy. Some actors classified the process
      as both insufficiently consultative and rushed. Due to limited consultation, it
      was suggested that the policy content did not adequately address key policy
      content issues such as management of staff attrition, general professional
      development, and progression matters. Analysis of the process also showed that
      the strategy might create a new group of workers whose mandate is unclear to the
      existing group of health workers. CONCLUSIONS: This paper highlights the complex
      nature of policy-making processes for integrating CHWs into the health system. It
      reiterates the need for recognising the fact that actors' power or position in
      the political hierarchy may, more than their knowledge and understanding of the
      issue, play a disproportionate role in shaping the process as well as content of
      health policy reform.

PMID- 23870455
TI  - MicroRNA-26a promotes tumor growth and angiogenesis in glioma by directly
      targeting prohibitin.
AB  - BACKGROUNDS AND AIMS: Glioma accounts for the majority of primary malignant brain
      tumors in adults. Upregulation of microRNA-26a (miR-26a) has been observed in
      glioma. However, the biological function and molecular mechanism of miR-26a in
      glioma remain to be elucidated. METHODS: Glioma cells stably overexpressing or
      down-expressing miR-26a were analyzed for both in vitro and in vivo biological
      functions. Novel target of miR-26a was identified by bioinformatics searching and
      molecular biological assays. Glioma specimens and normal brain tissues were
      analyzed for both expression levels of miR-26a and its target. RESULTS: Forced
      expression of miR-26a in glioma cells significantly increased both growth rate
      and colony formation in vitro and tumor growth and angiogenesis in vivo, while
      reduced expression of miR-26a played opposite roles. MiR-26a directly targeted
      prohibitin (PHB) whose expression levels were downregulated in glioma specimens.
      The levels of miR-26a were inversely correlated with PHB expression levels in
      glioma samples and strongly correlated with clinical WHO grades of glioma.
      CONCLUSION: These results reveal that miR-26a regulates PHB and promotes glioma
      progression both in vitro and in vivo and that miR-26a and its target PHB are
      associated with glioma development, which can be helpful in developing microRNA
      based treatment for glioma in the future.

PMID- 23870456
TI  - Hsp90 inhibitors in breast cancer: a systematic review.
AB  - PURPOSE: Pharmacological inhibition of Hsp90 shows great promise in breast cancer
      treatment. This is the first systematic review to synthesize all available data
      and to evaluate the efficacy and safety of Hsp90 inhibitors in breast cancer.
      METHODS: This study was performed in accordance with the PRISMA guidelines.
      Eligible articles were identified by a search of MEDLINE and ClinicalTrials.gov
      databases, using a predefined combination of the terms "breast", "cancer",
      "Hsp90", "inhibitors". RESULTS: Overall, 19 articles (190 patients) were
      eligible. The greatest clinical activity has been observed on the field of HER2
      positive metastatic breast cancer. However, accumulating data suggest that Hsp90
      inhibitors may play a significant role in the treatment of triple negative and
      aromatase inhibitor-resistant breast cancer. CONCLUSION: In the last decade, the
      development of Hsp90 inhibitors has moved forward rapidly; however, no phase III
      trials have been conducted and none agent has been approved for use in the
      clinical practice.

PMID- 23870457
TI  - Food consumption, physical activity and socio-economic status related to BMI,
      waist circumference and waist-to-height ratio in adolescents.
AB  - OBJECTIVE: To examine the association between obesity and food group intakes,
      physical activity and socio-economic status in adolescents. DESIGN: A cross
      sectional study was carried out in 2008. Cole's cut-off points were used to
      categorize BMI. Abdominal obesity was defined by a waist circumference at or
      above the 90th percentile, as well as a waist-to-height ratio at or above 0.500.
      Diet was evaluated using an FFQ, and the food group consumption was categorized
      using sex-specific tertiles of each food group amount. Physical activity was
      assessed via a self-report questionnaire. Socio-economic status was assessed
      referring to parental education and employment status. Data were analysed
      separately for girls and boys and the associations among food consumption,
      physical activity, socio-economic status and BMI, waist circumference and waist
      to-height ratio were evaluated using logistic regression analysis, adjusting the
      results for potential confounders. SETTING: Public schools in the Azorean
      Archipelago, Portugal. SUBJECTS: Adolescents (n 1209) aged 15-18 years. RESULTS:
      After adjustment, in boys, higher intake of ready-to-eat cereals was a negative
      predictor while vegetables were a positive predictor of overweight/obesity and
      abdominal obesity. Active boys had lower odds of abdominal obesity compared with
      inactive boys. Boys whose mother showed a low education level had higher odds of
      abdominal obesity compared with boys whose mother presented a high education
      level. Concerning girls, higher intake of sweets and pastries was a negative
      predictor of overweight/obesity and abdominal obesity. Girls in tertile 2 of milk
      intake had lower odds of abdominal obesity than those in tertile 1. Girls whose
      father had no relationship with employment displayed higher odds of abdominal
      obesity compared with girls whose father had high employment status. CONCLUSIONS:
      We have found that different measures of obesity have distinct associations with
      food group intakes, physical activity and socio-economic status.

PMID- 23870458
TI  - Chlamydia trachomatis infection of the male genital tract: an update.
AB  - Chlamydia trachomatis (CT) is the most prevalent cause of sexually transmitted
      diseases. Although the prevalence of chlamydial infection is similar in men and
      women, current research and screening are still focused on women, who develop the
      most severe complications, leaving the study of male genital tract (MGT)
      infection underrated. Herein, we reviewed the literature on genital CT infection
      with special focus on the MGT. Data indicate that CT certainly infects different
      parts of the MGT such as the urethra, seminal vesicles, prostate, epididymis and
      testis. However, whether or not CT infection has detrimental effects on male
      fertility is still controversial. The most important features of CT infection are
      its chronic nature and the presence of a mild inflammation that remains
      subclinical in most individuals. Chlamydia antigens and pathogen recognition
      receptors (PRR), expressed on epithelial cells and immune cells from the MGT,
      have been studied in the last years. Toll-like receptor (TLR) expression has been
      observed in the testis, epididymis, prostate and vas deferens. It has been
      demonstrated that recognition of chlamydial antigens is associated with TLR2,
      TLR4, and possibly, other PRRs. CT recognition by PRRs induces a local production
      of cytokines/chemokines, which, in turn, provoke chronic inflammation that might
      evolve in the onset of an autoimmune process in genetically susceptible
      individuals. Understanding local immune response along the MGT, as well as the
      crosstalk between resident leukocytes, epithelial, and stromal cells, would be
      crucial in inducing a protective immunity, thus adding to the design of new
      therapeutic approaches to a Chlamydia vaccine. 

PMID- 23870459
TI  - Young Hispanics at risk of type 2 diabetes display endothelial activation,
      subclinical inflammation and alterations of coagulation and fibrinolysis.
AB  - BACKGROUND: Hispanics have a high rate of diabetes that exposes them to an
      increased risk of cardiovascular disease. We hypothesized that many of the
      pathophysiological mechanisms that cause atherosclerotic disease may be present
      in young Hispanics who do not have clinical diabetes but are at increased risk of
      developing it. METHODS: We studied 36 young Hispanic adults without diabetes
      (ages 18-40). Seventeen participants were at increased risk of developing type 2
      diabetes given by overweight and a family history of diabetes on one or both
      parents (at risk group). Nineteen participants with normal body-mass index and no
      parental history of diabetes constituted the control group. We measured and
      compared plasma markers of endothelial dysfunction, disturbed coagulation and
      fibrinolysis, subclinical inflammation and adipose tissue dysfunction in the at
      risk and control groups. RESULTS: Participants at risk of diabetes were more
      insulin-resistant according to different indicators, and had significantly higher
      levels of soluble intercellular adhesion molecule-1 (sICAM-1), tissue plasminogen
      activator (tPA), inhibitor of plasminogen activator-1 (PAi-1), high sensitivity C
      reactive protein and free fatty acids, signaling the presence of multiple
      proatherogenic alterations despite the absence of overt diabetes. Levels of the
      prothrombotic molecule PAi-1 were most elevated in participants who were not only
      at risk of diabetes by the study definition, but also abdominally obese.
      CONCLUSIONS: Young adult Hispanics at risk of type 2 diabetes but without overt
      disease already bear considerably high levels of markers reflecting processes
      that lead to the development of atherosclerotic cardiovascular disease.

PMID- 23870460
TI  - Mass spectrometric U-series dating of Huanglong Cave in Hubei Province, Central
      China: evidence for early presence of modern humans in Eastern Asia.
AB  - Most researchers believe that anatomically modern humans (AMH) first appeared in
      Africa 160-190 ka ago, and would not have reached eastern Asia until ~50 ka ago.
      However, the credibility of these scenarios might have been compromised by a
      largely inaccurate and compressed chronological framework previously established
      for hominin fossils found in China. Recently there has been a growing body of
      evidence indicating the possible presence of AMH in eastern Asia ca. 100 ka ago
      or even earlier. Here we report high-precision mass spectrometric U-series dating
      of intercalated flowstone samples from Huanglong Cave, a recently discovered Late
      Pleistocene hominin site in northern Hubei Province, central China. Systematic
      excavations there have led to the in situ discovery of seven hominin teeth and
      dozens of stone and bone artifacts. The U-series dates on localized thin
      flowstone formations bracket the hominin specimens between 81 and 101 ka,
      currently the most narrow time span for all AMH beyond 45 ka in China, if the
      assignment of the hominin teeth to modern Homo sapiens holds. Alternatively this
      study provides further evidence for the early presence of an AMH morphology in
      China, through either independent evolution of local archaic populations or their
      assimilation with incoming AMH. Along with recent dating results for hominin
      samples from Homo erectus to AMH, a new extended and continuous timeline for
      Chinese hominin fossils is taking shape, which warrants a reconstruction of human
      evolution, especially the origins of modern humans in eastern Asia. 

PMID- 23870461
TI  - Effect of orthodontic force on inflammatory periodontal tissue remodeling and
      expression of IL-6 and IL-8 in rats.
AB  - OBJECTIVE: To investigate effect of orthodontic force on inflammatory periodontal
      tissue remodeling and expression of IL-6 and IL-8 in rats. METHODS: Eighty SD
      rats were randomly divided into 4 groups, blank control group (group A) with 5
      rats, treatment normal group (group B) with 25 rats, inflammation control group
      (group (group C) with 25 rats, inflammation treatment group (group D) with 25
      rats. Immunohistochemistry and histomorphometric analysis was performed to
      measure the expression of IL-6, IL-8 and the first molar to the recent movement
      in the distance. RESULTS: The expression of IL-8 reached a maximum on day 5 and
      declined thereafter in group B; the expression of IL-6 reached a maximum on day 5
      in group B. The expression of IL-6 and IL-8 was gradually weakened with time in
      group C. The expression of IL-6 and IL-8 were high, and reached a maximum on day
      5 and declined thereafter in group D. AD of positive cells in group D were higher
      than group B at each time point (P<0.05). The time which 0.49 N orthodontic force
      was loaded was longer, orthodontic tooth movement distance was greater. Movement
      distance in group D were longer than group B (P<0.05). CONCLUSIONS: Orthodontic
      force as well as inflammatory stimulus can evoke the expression of IL-6 and IL-8.
      Under the combined effects of inflammation and orthodontic force, the expression
      of IL-6, IL-8 will increase.

PMID- 23870462
TI  - Effects of recombinant adenovirus-mediated hypoxia-inducible factor-1alpha gene
      on proliferation and differentiation of endogenous neural stem cells in rats
      following intracerebral hemorrhage.
AB  - OBJECTIVE: To investigate the effects of adenovirus (Ad)-mediated hypoxia
      inducible factor-1alpha (HIF-1alpha) gene on proliferation and differentiation of
      endogenous neural stem cells (NSCs) in rats following intracerebral hemorrhage
      (ICH) and the underlying mechanisms. METHODS: A total of 120 specific pathogen
      free, adult, male Sprague-Dawley rats were included in this study. After
      establishment of ICH models in rats, PBS, Ad, or Ad-HIF-1alpha was administered
      via the ischemic ventricle. On the 1st, 7th, 14th, 21st and 28th d after ICH, rat
      neurological deficits were scored, doublecortin (DCX) expression in the
      subventricular zone cells was detected by immunohistochemical staining, and 5
      bromo-2'-deoxyuridine (BrdU)-, BrdU/DCX-, and BrdU/glial fibrillary acidic
      protein-positive cells in the subventricular zone were counted using
      immumofluorescence method among PBS, Ad, and Ad-HIF-1alpha groups. RESULTS: On
      the 7th, 14th, 21st and 28th d after ICH, neurological deficit scores in the Ad
      HIF-1alpha group were significantly lower than in the PBS and Ad groups (P<0.05).
      In the Ad-HIF-1alpha group, DCX expression was significantly increased on the 7th
      d, peaked on the 14th d, and then gradually decreased. In the Ad-HIF-1alpha
      group, BrdU-positive cells were significantly increased over time course, and
      significant difference in BrdU-positive cell counts was observed when compared
      with the PBS and Ad groups at each time point (P<0.01 or 0.05). On the 7th, 14th,
      21st and 28th d after ICH, the number of DCX-, BrdU-, BrdU/DCX-, and BrdU/DCX
      positive cells in the Ad-HIF-1alpha group was significantly greater than in the
      PBS and Ad groups (P<0.05). CONCLUSIONS: HIF-1alpha gene can promote the
      proliferation, migration and differentiation of endogenous neural stem cells
      after ICH, thereby contributing to neurofunctional recovery after ICH.

PMID- 23870463
TI  - Expression and significance of MMP-7, c-Jun and c-Fos in rats skin photoaging.
AB  - OBJECTIVE: To investigate the expression and significance of the MMP-7, c-Jun and
      c-Fos in rat photoaging skin. METHODS: A total of 45 SD rats were randomly
      divided into control group, model group, natural recovery group, physiological
      saline injection group and dermal pluripotent stem cells transplantation (DMSCs
      group), model group, natural recovery group, physiological saline injection
      group. DMSCs were treated with UV lamp irradiation to establish light aging skin
      model. Rats were then sacrificed after model prepared, no treatment was processed
      in the natural recovery group. Saline injections was adopted in saline group,
      DESCs group was treated with DESCs transplantation. Rats were sacrificed after 4
      weeks. The expression of MMP-7, c-Jun and c-Fos were detected using the
      immunohistochemical method. RESULTS: In model group, MMP 7 positive expression
      was higher than that in the other 4 groups, but without statistically difference
      (P>0.05); c-Jun, c-Fos expression were higher than that in the control group and
      DESCs group (P<0.05), there was no significant difference comparing natural
      recovery group with physiological saline injection group (P>0.05). CONCLUSIONS:
      MMP-7, c-Jun and c-Fos can be used as diagnosis indicators in the early stage of
      light aging, and they jointly participate in its development. DMSCs transplants
      is effective in treating light aging skin.

PMID- 23870464
TI  - Gastroprotective effect of the aqueous leaf extract of Guiera senegalensis in
      Albino rats.
AB  - OBJECTIVE: To evaluate the effect of aqueous leaf extract of Guiera senegalensis
      (G. senegalensis) on gastric mucosal damage using different ulcer models.
      METHODS: Considering the above claims, the present study was undertaken to
      validate the gastroprotective potential of the aqueous leaf extract of this plant
      against ethanol, water immersion and Aspirin induced ulcer models. RESULTS: The
      leaf extract (50, 100 and 200 mg/kg, p.o.) significantly (P<0.05) decreased the
      ulcer index in all assays used. CONCLUSIONS: The results obtained, provide strong
      evidence of antiulcer activity of the leaf extract of G. senegalensis and support
      the traditional uses of the plant for the treatment of ulcer.

PMID- 23870465
TI  - Cyathula prostrata: a potent source of anticancer agent against daltons ascites
      in Swiss albino mice.
AB  - OBJECTIVE: To evaluate the anticancer activity of the methanolic extract of
      Cyathula prostrata in Ehrlich ascites carcinoma (EAC)-bearing mice with
      methotrexate as positive control in the advanced stage of tumorigenesis. METHODS:
      EAC was induced in swiss albino mice by injecting 10(6) cell/mL of tumor cell
      suspension intraperitoneal. The methanolic extract of Cyathula prostrata effect
      on the tumor cell viability, DNA fragmentation and MTT assay were carried out.
      RESULTS: Methanolic extract attenuated percentage increased in the cell survival
      time when compared to control group. However, the effect was less than that of
      methotrexat. Methotrexat and the extracts reversed the tumor-induced alterations
      in DNA fragmentation and MTT assay. CONCLUSIONS: The present study suggests that
      the methanol extract of Cyathula prostrata has significant anticancer activity
      and that is comparable to that of methotrexate.

PMID- 23870466
TI  - Comparison of direct fecal smear microscopy, culture, and polymerase chain
      reaction for the detection of Blastocystis sp. in human stool samples.
AB  - OBJECTIVE: To compare the sensitivity and specificity of direct fecal smear
      microscopy, culture, and polymerase chain reaction in the detection of
      Blastocystis sp. in human stool. METHODS: Human stool samples were collected from
      a community in San Isidro, Rodriguez, Rizal, Philippines. These samples were
      subjected to direct fecal smear microscopy, culture and polymerase chain reaction
      to detect the presence of Blastocystis sp. RESULTS: Of the 110 stool samples
      collected, 28 (25%) were detected positive for the presence of Blastocystis sp.
      by two or more tests. Culture method detected the highest number of Blastocystis
      positive stool samples (n=36), followed by PCR of DNA extracted from culture
      (n=26), PCR of DNA extracted from stool (n=10), and direct fecal smear (n=9).
      Compared to culture, the sensitivity of the other detection methods were 66.7%
      for PCR from culture and 19.4% for both PCR from stool and direct fecal smear.
      Specificity of the methods was high, with PCR from culture and direct fecal smear
      having 97.3%, while PCR from stool at 95.9%. CONCLUSIONS: In this study, in vitro
      culture is the best method for detecting Blastocystis sp. in human stool samples.

PMID- 23870467
TI  - Evaluation of extracts and essential oil from Callistemon viminalis leaves:
      antibacterial and antioxidant activities, total phenolic and flavonoid contents.
AB  - OBJECTIVE: To investigate antioxidant and antibacterial activities of Callistemon
      viminalis (C. viminalis) leaves. METHODS: The essential oil of C. viminalis
      leaves obtained by hydro-distillation was analyzed by GC/MS. Different extracts
      were tested for total phenolic and flavonoid contents and in vitro antioxidant
      (DPPH assay) and antibacterial (agar disc diffusion and 96-well micro-plates
      methods) actives. RESULTS: Fourteen components were identified in the essential
      oil, representing 98.94% of the total oil. The major components were 1,8-cineole
      (64.53%) and alpha-pinene (9.69%). Leaf essential oil exhibited the highest
      antioxidant activity of (88.60+/-1.51)% comparable to gallic acid, a standard
      compound [(80.00+/-2.12)%]. Additionally, the biggest zone of inhibitions against
      the studied bacterial strains was observed by the essential oil when compared to
      the standard antibiotic (tetracycline). The crude methanol extract and ethyl
      acetate fraction had a significant antibacterial activity against the tested
      bacterial strains. CONCLUSIONS: It can be suggested that C. viminalis is a great
      potential source of antibacterial and antioxidant compounds useful for new
      antimicrobial drugs from the natural basis. The present study revealed that the
      essential oil as well as the methanol extracts and ethyl acetate fraction of C.
      viminalis leaves exhibited highly significant antibacterial activity against the
      tested bacterial strains.

PMID- 23870468
TI  - Molecular characterization of sandflies and Leishmania detection in main vector
      of zoonotic cutaneous leishmaniasis in Abarkouh district of Yazd province, Iran.
AB  - OBJECTIVE: To assess molecular characterization, distribution, seasonal
      activities of sandfly species and Leishmania parasites infecting them for this
      zoonotic cutaneous leishmaniasis focus. METHODS: The collections were carried out
      in 2009-2011 using CDC traps, Sticky Papers and manual aspirator in and around
      the villages in Abarkouh district. Individual sandflies were characterized by PCR
      amplification and sequencing of fragments of their mitochondrial cytochrome b
      gene. Leishmania parasite infections within sandflies were performed by targeting
      Cyt b, ITS-rDNA, k-DNA and microsatellite genes. RESULTS: The PCR assays detected
      only Leishmania major (L. major). All infections (30) were found in the abundant
      and widespread vector Phlebotomus papatasi (P. papatasi). Small numbers of other
      sandfly species were also screened for infections, but none was found.
      Sergentomyia sintoni and P. papatasi were the predominant members in all
      locations of this district and in all habitats throughout the trapping season.
      Only five other sandfly species were found, namely Phlebotomus ansari,
      Phlebotomus caucasicus, Phlebotomus sergenti, Sergentomyia dentata and
      Sergentomyia merviney. CONCLUSIONS: In the current survey, the only infections
      detected are of L. major in females of P. papatasi (30 out of 190). The rates of
      infection of P. papatasi by L. major are not significantly different in compare
      with other locations in Iran with no diversity of parasite strains. Zoonotic
      cutaneous leishmaniasis may have emerged only recently in Abarkouh district, and
      the reason may well be the instability of the transmission cycles there.

PMID- 23870469
TI  - Synthesis and evaluation of monoclonal antibody against Plasmodium falciparum
      merozoite surface antigen 2.
AB  - OBJECTIVE: To assess the quality of expressed MSP-2 and also to confirm the
      immune response against different domains of these proteins. METHODS: Mice were
      immunized with a schizont extract to stimulate the immune system to make
      antibodies against different antigens of the late stage parasite including
      production of antibodies against different domains of Plasmodium falciparum (P.
      falciparum) MSP-2. B lymphocytes of immunized mice were extracted from the spleen
      and the fusion was performed using NS-1 myeloma cells and the hybridoma cells
      were assayed by ELISA either with a schizont extract or different domains of MSP
      2 and/or by IFAT with whole schizont preparation. Fusion of NS-1 and spleen cells
      was performed. The positive hybrids were cloned and ELISA was applied against
      different dilutions. The positive clones were transferred to a small tissue
      culture flask and after developing they were assayed against schizont extract and
      the different MSP-2 domains. The positive clones were expanded to large (75
      cm(2)) flask and cultured under the same conditions, checking them using both
      ELISA and IFAT and the positive cells were frozen as soon as possible. RESULTS: A
      total number of 7 fusions including 26 plates (2 496 wells) were performed, of
      which 1 336 hybrids were produced and the overall efficiency (1 336/2496 * 100)
      was about 53%. ELISA was performed to detect the positive hybrids against crude
      schizont extract by which the highest frequency to crude schizont extract was
      found for the supernatant of the hybrids produced in fusion number 3 (66 out of
      315 hybrids). The supernatant of both B5 and F1 hybridoma cells were more
      positive against domain 2 of the MSP-2 recombinant protein in Western blotting
      test. Western blotting results also showed that different domains of the MSP-2
      recombinant protein and also the MSP-2 of the P. falciparum parasite were
      recognized by some of the positive clones and also immune sera. CONCLUSIONS:
      Bringing together all the results of this study it has been confirmed that some
      clones have recognized both schizont extract and different domains of the MSP-2
      recombinant protein and therefore confirming the quality of the MSP-2 domains.

PMID- 23870470
TI  - Cytoprotective, antihyperglycemic and phytochemical properties of Cocos nucifera
      (L.) inflorescence.
AB  - OBJECTIVE: To analyze the cytoprotective and antidiabetic activities as well as
      phytochemical composition of the immature inflorescence of Cocos nucifera
      belonging to the Arecaceae Family. METHODS: The phytochemical screening of
      inflorescence was done to determine the major constituents present in Cocos
      nucifera inflorescence. The free radical scavenging potential of inflorescence
      extracts were evaluated using in vitro radical scavenging assay models. RESULTS:
      The phytochemical analyses on inflorescence showed the presence of phenolic
      compounds, flavonoids, resins and alkaloids. The macronutrient analyses, on the
      other hand, showed the presence of carbohydrate, proteins and fibers.
      Administration of the methanol extract of coconut inflorescence to the diabetic
      rats showed dose dependent reduction in hyperglycemia. The cytoprotective
      property of coconut inflorescence was evidenced from the acute toxicological
      evaluation. The levels of serum aspartate aminotransferase, alanine
      aminotransferase, and alkaline phosphatase were significantly decreased in the
      diabetic rats treated with inflorescence when compared with the diabetic control
      rats. CONCLUSION: The results obtained from the present study apparently proved
      the non-toxic nature and the cytoprotective and antihyperglycemic properties of
      coconut inflorescence.

PMID- 23870471
TI  - Assessment of genotoxicity and cytotoxicity of standardized aqueous extract from
      leaves of Erythroxylum cuneatum in human HepG2 and WRL68 cells line.
AB  - OBJECTIVE: To investigate the cytotoxicity and the genotoxicity of standardized
      aqueous of dry leaves of Erythroxylum cuneatum (E. cuneatum) in human HepG2 and
      WRL68 cells. METHODS: The cytotoxicity of E. cuneatum extract was evaluated by
      both MTS and LDH assays. Genotoxicity study on E. cuneatum extract was assessed
      by the single cell gel electrophoresis (comet assay). The protective effect of E.
      cuneatum against menadione-induced cytotoxicity was also investigated. RESULTS:
      Results from this study showed that E. cuneatum extract exhibited cytotoxic
      activities towards the cells with IC50 value of (125+/-12) and (125+/-14) MUg/mL
      for HepG2 and WRL68 cells respectively, after 72 h incubation period as
      determined by MTS assay. LDH leakage was detected at (251+/-19) and (199.5+/
      12.0) MUg/mL for HepG2 and WRL68 respectively. Genotoxicity study results showed
      that treatment with E. cuneatum up to 1 mg/mL did not cause obvious DNA damage in
      WRL68 and HepG2 cells. Addition of E. cunaetum did not show significant
      protection towards menadione in WRL68 and HepG2 Cells. CONCLUSIONS: E. cuneatum
      standardized aqueous extract might be developed in order to establish new
      pharmacological possibilities for its application.

PMID- 23870472
TI  - The study of KBP of road construction workers of highway AIDS prevention project
      before and after intervention.
AB  - OBJECTIVE: To get scientific basis for further health education through the
      research of the road construction workers' KBP before and after the interventions
      of highway AIDS prevention project. METHODS: Multi-stage random sampling method
      was employeed to select workers of 8 sites from 14 sites along highway to
      investigate their AIDS knowledge, belief and performance (KBP) before and after
      highway AIDS prevention project. RESULTS: Over 90% of the investigated workers
      had ever heard about AIDS, and the non-skilled workers of lower educational level
      improved more after intervention. The correct answer rate of the three
      transmitting ways of AIDS of drivers which is the focused group of highway before
      and after intervention had the obvious statistical significance (P<0.05), and the
      other group's correct answer rates also had improved after intervention. Most
      people's understanding of preventing AIDS through correct use of condoms when
      having sex had a statistically significant difference(P<0.05) after prevention.
      The rates of using condoms of foremen and skilled workers when having sex with
      commercial sex worker/casual partner increased after intervention. CONCLUSIONS:
      The health education of HIV among the road construction workers is effective and
      further health education of HIV prevention should be carried out among the road
      construction workers to improve their knowledge and awareness of avoiding the
      high-risk behaviors.

PMID- 23870473
TI  - Brucellosis and tuberculosis: clinical overlap and pitfalls.
AB  - OBJECTIVE: To identify characteristic features of tuberculosis in patients with
      culture proven brucellosis. METHODS: A retrospective analysis was performed on
      patients diagnosed with culture proven brucellosis between January and December
      2011, based on review of their medical records. Patients with demonstrable co
      infection with tuberculosis were excluded. Clinical features, laboratory
      parameters and tissue histopathology reports where available were noted. RESULTS:
      Thirty-two patients with brucellosis were included in the study. Twenty-one
      (65.63%) patients had chronic fever, thirteen (40.63%) had a productive cough,
      while significant weight loss, evening rise of temperature and night sweats were
      reported by eight (25.00%), eleven (34.38%) and five (15.63%) patients
      respectively. Nine (28.13%) patients had at least three of these symptoms.
      Lymphadenopathy, hepatomegaly and splenomegaly were noted on examination in seven
      (21.88%), fifteen (46.88%) and twelve (37.50%) patients respectively. Eight
      (25.00%) patients had hepato-splenomegaly, of these only two had associated
      significant lymphadenopathy. Respiratory examination was normal in all patients.
      Elevated ESR greater than 50 mm/hr was seen in eight (25.00%), it was greater
      than 100 mm/hr in five (15.63%) patients. Hypergammaglobulinemia was seen in
      eight (25.00%) cases. Bone marrow biopsy showed non-caseating granulomas in three
      (9.38%) cases, lymph node biopsy showed granulomas in one case. Overall, three
      (9.38%) patients had known risk factors for tuberculosis, while six (18.75%) had
      risk factors for brucellosis. CONCLUSIONS: There is a clear overlap between
      brucellosis and tuberculosis both in terms of clinical presentation and
      laboratory parameters. It is essential to carefully rule out tuberculosis in all
      cases of suspected or proven brucellosis before initiating antimicrobial therapy,
      in order to forestall development of drug-resistant tuberculosis.

PMID- 23870474
TI  - Estrogen up-regulates MMP2/9 expression in endometrial epithelial cell via VEGF
      ERK1/2 pathway.
AB  - OBJECTIVE: To study the effect of estrogen on anovulatory dysfunctional uterine
      bleeding (ADUB). METHODS: Primary endometrial epithelial cells of Hainan Lizu
      female was cultured and hydrolytic activity of gelatinase was determined by
      gelatin zymography analysis. Cellular mRNA and protein synthesis was blocked
      respectively to determine whether the increased expression of MMP-2/9 was induced
      by estrogen. The expression of VEGF was blocked by siRNA. After treatment with
      various factors, MMP-9, VEGF, total Erk and phosphorylated Erk expression in
      primary uterine epithelial cells was detected by Western blotting analysis. Cell
      MMP-2/9mRNA levels was measured by real-time RT-PCR. RESULTS: The activity and
      expression of MMP2/9 was increased in the endometrium of patients with ADUB.
      Estrogen could up-regulate the expression of VEGF and activate Erk 1/2-Elk1
      signal path. After interference by siRNA, ERK1/2 pathway was blocked in cells,
      and the expression of MMP-2/9 was down-regulated. ERK1/2 specific blocker U0126
      blocked ERK phosphorylation, and it could down-regulate the expression of MMP
      2/9. CONCLUSIONS: The results showed that the estrogen can increase the
      expression of VEGF, and thus activate ERK1/2 pathway to induce MMP-2/9
      expression.

PMID- 23870475
TI  - Expression and significance of p53 and mdm2 in patients with leukoplakia cancer.
AB  - OBJECTIVE: To study the relationship of the expressions of p53 and mdm2 in
      leukoplakia cancer. METHODS: RT-PCR was used to detect the mRNA of p53, mdm2 in
      patients with leukoplakia cancer. The frequencies of p53, mdm2 in peripheral
      blood were detected by flow cytometric analysis. RESULTS: The expression of
      p53mRNA in normal oral mucosa, simple oral leukoplakia, no-simple oral
      leukoplakia and leukoplakia cancer were 7.7%, 27.3%,33.3%, 56.8%, respectively.
      The frequencies of p53 in normal oral mucosa, simple oral leukoplakia, no-simple
      oral leukoplakia and leukoplakia cancer were (0.3+/-0.1)%, (1.6+/-0.9)%, (1.9+/
      1.1)%, (3.4+/-1.8)%. The expression of mdm2 mRNA in normal oral mucosa, simple
      oral leukoplakia, no-simple oral leukoplakia and leukoplakia cancer were 0.0%,
      6.8%, 11.1%, 37.8%, respectively. The frequencies of mdm2 in normal oral mucosa,
      simple oral leukoplakia, no-simple oral leukoplakia and leukoplakia cancer were
      (0.1+/-0.1)%, (0.8+/-0.6)%, (1.2+/-0.8)%, (1.2+/-0.8)%. There was a positively
      correlation between p53 mRNA and mdm2 mRNA. CONCLUSIONS: The positive rate of p53
      and mdm2 cells in the peripheral blood increases in patients with leukoplakia
      cancer tissue and has positive correlation with the severity of leukoplakia
      cancer.

PMID- 23870476
TI  - Relationship between CYP1A1 polymorphisms and invasion and metastasis of breast
      cancer.
AB  - OBJECTIVE: To investigate the relationship between CYP1A1 genetic polymorphisms
      and the invasion and metastasis of breast cancer. METHODS: The CYP1A1 gene
      polymorphism (an T-C transversion at nucleotide position 3801) was detected by
      the polymerase chain reaction and restriction fragment length polymorphism in 80
      cases with breast cancer and 60 samples of normal breast tissue. The difference
      in genotypic distribution frequency between the groups, the correlation between
      the genotypes and the factors related to prognosis were analyzed. RESULTS: The
      incidence of homozygous and variant genotypes had no difference between the
      breast cancer group and controls group (P=0.746). The proportion of variant
      genotype increased as clinical stage (P=0.006) advanced, as well as with
      increased numbers of lymph node metastases (P=0.010). CONCLUSIONS: In patients
      with breast cancer there is a correlation between the CYP1A1 CC allele and some
      factors indicating poor prognosis, including more lymph node metastases as well
      as a more advanced clinical stage.

PMID- 23870477
TI  - Atypical respiratory complications of dengue fever.
AB  - In last decade, dengue has emerged as one of the most important vector born
      disease. With increasing cases, uncommon presentations and complications are now
      commonly recognized. Here, we report two cases of rare pattern of respiratory
      involvement in dengue: acute respiratory distress syndrome and bronchiolitis with
      respiratory failure. 

PMID- 23870479
TI  - How will focal therapy fit in with existing treatments?
AB  - CONTEXT: The current management of localized prostate cancer is a therapeutic
      challenge with different options including active radicals or active follow-up.
      The aim of this paper is to analyze the feasibility and validity of the "Focal"
      active treatment versus the concept of active follow-up or Radical Treatment.
      EVIDENCE ACQUISITION: We reviewed the literature on the various diagnostic
      methods, advantages, and difficulties of active follow-up and Radical Treatment,
      versus focal therapy with the possibilities of defining characteristics of
      aggressiveness and patient selection. EVIDENCE SYNTHESIS: The mesh biopsy
      techniques along with multiparametric magnetic resonance imaging and association
      of factors such as tumor size, length of affected cylinder and Gleason are
      parameters that allow us to define location and definition of clinically
      significant tumors and subsidiary of focal therapies. CONCLUSIONS: The
      definition, location and aggressiveness of prostate cancer in low-intermediate
      risk tumors can be defined avoiding radical therapies with their side effects or
      the risks of underestimating tumors as in active follow-up without the minimum
      side effects.

PMID- 23870480
TI  - Implementation of a protocol proposed by the Brazilian National Health
      Surveillance Agency for antibiotic use in very low birth weight infants.
AB  - OBJECTIVE: To analyze the implementation of a protocol proposed by the Brazilian
      National Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria -
      ANVISA) to improve sepsis diagnosis in very low birth weight newborns. METHODS:
      This was a prospective study that evaluated the implementation of a protocol
      involving clinical and laboratory criteria (hematologic scoring system of Rodwell
      and C-reactive protein serial measurements), recommended by ANVISA, to improve
      the diagnosis of neonatal sepsis in very low birth weight newborns. The study
      included all patients who were born and remained in the neonatal intensive care
      unit until discharge or death, and excluded those with congenital diseases. The
      main outcomes measured in newborns before (2006-2007) and after implementation of
      the protocol (2008) were the rates of early and late-onset sepsis, use of
      antibiotics, and mortality. Means were compared by Student's t-test and
      categorical variables were compared by the chi-squared test; the significance
      level for all tests was set at 95%. RESULTS: The study included 136 newborns with
      very low birth weight. There was no difference between groups regarding general
      clinical characteristics in the studied periods. There was, however, a decrease
      in the number of diagnoses of probable early-onset sepsis (p<0.001), use of
      antimicrobial regimens (p<0.001), and overall mortality and infection-related
      mortality (p=0.009 and p=0.049, respectively). CONCLUSION: The implementation of
      the protocol allowed improvement of sepsis diagnosis by reducing the diagnosis of
      probable early-onset sepsis, thus promoting efficient antimicrobial use in this
      population.

PMID- 23870481
TI  - Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and
      death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced
      diabetic rats partially by regulating endoplasmic reticulum stress.
AB  - BACKGROUND: It is increasingly being realized that failure of pancreatic beta
      cells to secrete enough insulin to adequately compensate for obesity and insulin
      resistance is the primary defects of type 2 diabetes mellitus (T2DM). Pancreatic
      beta cells possess a highly developed and active endoplasmic reticulum (ER),
      reflecting their role in folding, export and processing of newly synthesized
      insulin. ER stress-induced pancreatic beta-cell failure is a novel event in the
      pathogenesis of T2DM. Some studies with antioxidants indicated a beneficial
      impact on ER stress. Our previous study found that strong antioxidants, grape
      seed proanthocyanidins (GSPs), ameliorated ER stress to protect skeletal muscle
      from cell death in type 2 diabetic rats. The present study continued to
      investigate the effect of GSPs on beta-cell failure and ER stress in diabetic
      pancreas. METHODS: Male Sprague-Dawley rats made type 2 diabetic with 2
      injections of 25 mg/kg streptozotocin and 8 weeks of the high-carbohydrate/high
      fat diet were fed a basal diet with or without GSPs administration for 16 weeks.
      Oral glucose tolerance, plasma glucose, serum insulin and the score of beta-cell
      function were measured. Morphological observation was performed by light and
      electron microscopic analyses. Islet cell apoptosis was determined by terminal
      deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling staining.
      Additionally, the level of insulin and the expression of ER stress markers in
      pancreatic islets were also studied using immunohistochemical staining. RESULTS:
      After 16 weeks treatment, the score of beta-cell function and the abnormal oral
      glucose tolerance of diabetic rats were partially reversed by GSPs treatment. The
      efficacious effect of GSPs was also manifested in the amelioration of pancreatic
      damage and ER dilatation by microscopic analyses. Moreover, GSPs treatment
      increased normal insulin content and decreased the number of apoptotic cells in
      diabetic islets. Importantly, GSPs treatment partially alleviated ER stress by
      decreasing some ER stress markers. CONCLUSION: These findings suggest that GSPs
      might have auxiliary therapeutic potential for pancreatic beta-cell dysfunction
      and death in T2DM.

PMID- 23870482
TI  - Novel members of the AGAMOUS LIKE 6 subfamily of MIKCC-type MADS-box genes in
      soybean.
AB  - BACKGROUND: The classical (C) MIKC-type MADS-box transcription factors comprise
      one gene family that plays diverse roles in the flowering process ranging from
      floral initiation to the development of floral organs. Despite their importance
      in regulating developmental processes that impact crop yield, they remain largely
      unexplored in the major legume oilseed crop, soybean. RESULTS: We identified 57
      MIKC(c)-type transcription factors from soybean and determined the in silico gene
      expression profiles of the soybean MIKC(c)-type genes across different tissues.
      Our study implicates three MIKC(c)-type transcription factors as novel members of
      the AGAMOUS LIKE 6 (AGL6) subfamily of the MIKC(C)-type MADS-box genes, and we
      named this sister clade PsMADS3. While similar genes were identified in other
      legume species, poplar and grape, no such gene is represented in Arabidopsis
      thaliana or rice. RT-PCR analysis on these three soybean PsMADS3 genes during
      early floral initiation processes revealed their temporal expression similar to
      that of APETALA1, a gene known to function as a floral meristem identity gene.
      However, RNA in situ hybridisation showed that their spatial expression patterns
      are markedly different from those of APETALA1. CONCLUSION: Legume flower
      development system differs from that in the model plant, Arabidopsis. There is an
      overlap in the initiation of different floral whorls in soybean, and inflorescent
      meristems can revert to leaf production depending on the environmental
      conditions. MIKC(C)-type MADS-box genes have been shown to play key regulatory
      roles in different stages of flower development. We identified members of the
      PsMADS3 sub-clade in legumes that show differential spatial expression during
      floral initiation, indicating their potential novel roles in the floral
      initiation process. The results from this study will contribute to a better
      understanding of legume-specific floral developmental processes.

PMID- 23870483
TI  - Changes in school environment, awareness and actions regarding overweight
      prevention among Dutch secondary schools between 2006-2007 and 2010-2011.
AB  - BACKGROUND: Schools can be an important setting for the prevention of overweight.
      This nation-wide survey investigated changes in the obesogenity of the school
      environment, the awareness of schools regarding overweight, school health policy,
      and actions taken by schools to prevent overweight. METHODS: In 2006/2007 and
      2010/2011, questionnaires were sent to all Dutch secondary schools, (n = 1250 and
      n = 1145, response rate 44% and 33% respectively, repeated data for 187 schools).
      RESULTS: The percentage of schools with vending machines for soft drinks (~90%)
      and sweets (~80%) remained fairly stable, whereas slightly more schools indicated
      to have a canteen (87%-91%). The food supply was reported to be healthier in
      2010/2011 compared to 2006/2007. Canteens and/or vending machines offered more
      often fresh fruits (+8%), sandwiches (+11%), water (+11%) and salad (+7%) and
      less often sugar sweetened soft drinks (-10%). However, unfavorable changes such
      as an increase in the supply of pizza slices (+13%) and milk and yoghurt drinks
      with added sugar (+12%) were also reported. Between 2006/2007 and 2010/2011, the
      presence of water coolers increased (12% versus 33%) as well as facilities for
      physical activity (67% versus 77%). However, more schools had vending places of
      unhealthy foods in the vicinity (73% versus 85%). Compared to 2006/2007, a higher
      percentage of schools indicated that they have taken actions to stimulate healthy
      eating behavior (72% versus 80%) or to prevent overweight (34% versus 52%) in
      2010/2011. Less schools indicated that they expect to pay more attention to
      overweight prevention in the near future (56% versus 43%), but none of them
      expected to pay less attention. CONCLUSIONS: Several aspects of the school
      environment changed in a positive way. However, schools should be encouraged to
      contribute to the prevention of overweight, or to continue to do so.

PMID- 23870484
TI  - Release and uptake of volatile organic compounds by human hepatocellular
      carcinoma cells (HepG2) in vitro.
AB  - BACKGROUND: Volatile organic compounds (VOCs) emitted by human body offer a
      unique insight into biochemical processes ongoing in healthy and diseased human
      organisms. Unfortunately, in many cases their origin and metabolic fate have not
      been yet elucidated in sufficient depth, thus limiting their clinical
      application. The primary goal of this work was to identify and quantify volatile
      organic compounds being released or metabolized by HepG2 hepatocellular carcinoma
      cells. METHODS: The hepatocellular carcinoma cells were incubated in specially
      designed head-space 1-L glass bottles sealed for 24 hours prior to measurements.
      Identification and quantification of volatiles released and consumed by cells
      under study were performed by gas chromatography with mass spectrometric
      detection (GC-MS) coupled with head-space needle trap device extraction (HS-NTD)
      as the pre-concentration technique. Most of the compounds were identified both by
      spectral library match as well as retention time comparison based on standards.
      RESULTS: A total of nine compounds were found to be metabolised and further
      twelve released by the cells under study (Wilcoxon signed-rank test, p<0.05). The
      former group comprised 6 aldehydes (2-methyl 2-propenal, 2-methyl propanal, 2
      ethylacrolein, 3-methyl butanal, n-hexanal and benzaldehyde), n-propyl
      propionate, n-butyl acetate, and isoprene. Amongst the released species there
      were five ketones (2-pentanone, 3-heptanone, 2-heptanone, 3-octanone, 2
      nonanone), five volatile sulphur compounds (dimethyl sulfide, ethyl methyl
      sulfide, 3-methyl thiophene, 2-methyl-1-(methylthio)- propane and 2-methyl-5
      (methylthio) furan), n-propyl acetate, and 2-heptene. CONCLUSIONS: The emission
      and uptake of the aforementioned VOCs may reflect the activity of abundant liver
      enzymes and support the potential of VOC analysis for the assessment of enzymes
      function.

PMID- 23870485
TI  - Transcription factor NFkappaB regulates the expression of the histone deacetylase
      SIRT1.
AB  - BACKGROUND: The NAD-dependent protein deacetylase SIRT1 has a wide range of
      different targets, which may be regulated either directly through deacetylation
      and thus potentially altering their activity or localization or indirectly by
      deacetylation of histones, which in turn alters their transcription rate and
      availability. SIRT1 is therefore involved in the regulation of many different and
      fundamental cellular processes such as apoptosis, metabolism, differentiation and
      cell cycle arrest. It is also involved in the regulation of resistance of cells
      against oxidative stress and longevity under conditions of caloric restriction.
      Even though the targets and role of SIRT1 have been studied quite intensively,
      only little is known about the mechanisms affecting SIRT1 transcriptional
      regulation. The nuclear factor NFkappaB is a well-studied and widely known
      transcription factor, which is involved in the regulation of many important
      cellular activities. The regulation of NFkappaB by SIRT1 has been reported
      recently, but it is, however, still unknown whether a feedback mechanism affects
      the regulation of SIRT1 too, particularly in view of the fact that putative
      NFkappaB binding sites within the SIRT1 promoter suggest just that. RESULTS: In
      the study presented herein we show that there is activation of the SIRT1 promoter
      by overexpression of different NFkappaB subunits. Direct binding of NFkappaB to
      the SIRT1 promoter can be demonstrated by an electrophoretic mobility shift
      assay. Further investigations indicated enhanced expression of SIRT1 on the mRNA
      levels in cells overexpressing NFkappaB. A functional assay showed that
      acetylation of one of the main target proteins of SIRT1 is reduced in these
      cells. CONCLUSIONS: These finding together indicate SIRT1 expression to be
      regulated in a positive feedback loop by NFkappaB. The putative binding sites for
      NFkappaB found within the SIRT1 promoter appears to be functional and several
      NFkappaB subunits are able to enhance the expression of SIRT1 if they are
      overexpressed.

PMID- 23870486
TI  - Hormones of adipose tissue and their biologic role in lung cancer.
AB  - INTRODUCTION: Adipose tissue secretes numerous bioactive peptides, collectively
      termed "adipocytokines" or "adipokines". Adipokines act in a paracrine,
      autocrine, or endocrine manner and regulate several physiological and
      pathological processes. Increasing evidence indicates that adipokines are
      implicated also in several malignancies, including lung cancer as well. AIM: The
      aim of this study is to summarize data concerning adipokines in lung cancer
      pathogenesis, prognosis and survival; the role of adipokines in lung cancer
      cachexia is also examined. MATERIALS AND METHODS: A systematic literature search
      was performed in the electronic database of Medline. Several studies and review
      articles met the inclusion criteria. RESULTS: Leptin and adiponectin are the best
      studied adipokines. The majority of the relevant studies has investigated the
      potential correlations mainly between leptin, adiponectin, and sometimes also
      resistin, and nutritional status, systemic inflammation of lung cancer or lung
      cancer cachexia and have also assessed their prognostic significance. Few other
      studies have studied genetic variations in leptin, leptin receptor and
      adiponectin genes and their association with lung cancer susceptibility and
      prognosis. The ongoing list of adipokines associated with lung cancer also
      includes resistin, chemerin, and visfatin. CONCLUSIONS: Increasing evidence
      points to the involvement of certain adipocytokines in lung cancer development,
      progression and prognosis. No conclusive evidence exists so far with regards to
      the role of adipocytokines in lung cancer cachexia. Future, longitudinal studies
      are warranted in order to clarify the role of adipocytokines in lung cancer and
      also uncover adipocytokines as novel therapeutic targets.

PMID- 23870487
TI  - Alteration of functional loads after tongue volume reduction.
AB  - OBJECTIVES: An earlier study revealed that the patterns of biomechanical loads on
      bones around the tongue altered significantly right after tongue volume reduction
      surgery. The current study was to examine whether these alterations persist or
      vanish over time post-surgery. DESIGN: Five sibling pairs of 12-week-old Yucatan
      minipigs were used. For each pair, one had surgery reducing tongue volume by
      about 15% (reduction) while the other had same incisions without tissue removal
      (sham). All animals were raised for 4 weeks after surgery. Three rosette strain
      gauges were placed on the bone surfaces of pre-maxilla (PM), mandibular incisor
      (MI), and mandibular molar (MM); two single-element gauges were placed across the
      pre-maxilla-maxillar suture (PMS) and mandibular symphysis (MSP), and two
      pressure transducers were placed on the bone surfaces of hard palate (PAL) and
      mandibular body (MAN). These bone strains and pressures were recorded during
      natural mastication. RESULTS: Overall amount of all loads increased significantly
      as compared to those in previous study in all animals. Instead of decreased loads
      in reduction animals as seen in that study, shear strains at PM, MI, and MM,
      tensile strains at PMS, and pressure at MAN were significantly higher in
      reduction than sham animals. Compared to the sham, strain dominance shifted at
      PM, MI, and MM and orientation of tensile strain altered at MI in reduction
      animals. CONCLUSION: A healed volume-reduced tongue may change loading regime
      significantly by elevating loading and altering strain-dominant pattern and
      orientation on its surrounding structures, and these changes are more remarkable
      in mandibular than maxillary sites.

PMID- 23870488
TI  - A cross-sectional study of age-related changes in plantar pressure distribution
      between 4 and 7 years: a comparison of regional and pixel-level analyses.
AB  - Quantifying morphological and functional development in children's feet, and
      thereby establishing development norms is difficult. In addition to practical
      challenges of experimentation on children, measurement equipment like plantar
      pressure (PP) platforms are almost exclusively geared towards adult-sized feet.
      These PP quantification problems may be exacerbated by typical regional data
      analysis techniques, which further reduce spatial resolution. The goal of this
      study was to quantify PP distributions in developing children, and also to
      compare the results obtained from typical (regional) techniques with those
      obtained from a higher-resolution (pixel-level) technique. Ninety-eight children
      between four and seven years of age were assessed in a cross-sectional design.
      Maximum PP distributions were collected for each child, and these pressures were
      linearly regressed against age. Present results agree with previous
      investigations in that maximum pressures and maximum pressure changes occurred in
      the forefoot. However, results from the present pixel-level technique suggest
      that these changes are limited to the central metatarsals, and that regional
      methods can suggest significance where none exists in the actual raw (pixel
      level) data, due to signal aliasing and, in particular, to conflation of regional
      boundaries. We postulate that increased central metatarsal pressures are
      reflective of the coupling between generalised joint laxity decreases and
      relatively increasingly inclined central metatarsal bones with age. 

PMID- 23870489
TI  - Upregulation of glutamate-aspartate transporter by glial cell line-derived
      neurotrophic factor ameliorates cell apoptosis in neural retina in streptozotocin
      induced diabetic rats.
AB  - AIMS: Dysfunction of glutamate uptake, largely mediated by the glutamate
      aspartate transporter (GLAST), may lead to retinal cell apoptosis in diabetic
      retinopathy. The aim of this study is to examine how cell apoptosis and the
      expression level of GLAST in neural retina of a diabetic rat model are changed
      and whether the neuroretinal apoptosis could be ameliorated by the administration
      of glial cell line-derived neurotrophic factor (GDNF). METHODS: Diabetes was
      induced by intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley
      rats. GLAST protein expression levels were determined by Western blotting,
      whereas apoptosis of retinal neurons was evaluated by TUNEL staining. To assess
      the role of GDNF in ameliorating the STZ-induced retinal changes, GDNF/GDNF with
      siRNA directed against GLAST was injected into the vitreous after STZ injection.
      RESULTS: In rat retinas 4 weeks after the onset of STZ-induced diabetes, TUNEL
      positive cells were significantly increased, whereas GLAST levels were
      significantly reduced. Intraocular administration of GDNF at the early stage of
      diabetes remarkably increased the GLAST levels and decreased TUNEL-positive
      signals in the retinas. These effects of GDNF were largely abolished by
      coadministration of GLAST siRNA. CONCLUSIONS: GDNF, administrated at the early
      stage of diabetes, could rescue retinal cells from neurodegeneration by
      upregulating the expression of GLAST.

PMID- 23870490
TI  - Olfactory identification deficits and associated response inhibition in obsessive
      compulsive disorder: on the scent of the orbitofronto-striatal model.
AB  - Olfactory identification ability implicates the integrity of the orbitofrontal
      cortex (OFC). The fronto-striatal circuits including the OFC have been involved
      in the neuropathology of Obsessive Compulsive Disorder (OCD). However, only a few
      studies have examined olfactory function in patients with OCD. The Brief Smell
      Identification Test (B-SIT) and tests from the Cambridge Neuropsychological
      Automated Battery (CANTAB) were administered to 25 patients with OCD and to 21
      healthy matched controls. OCD patients showed a significant impairment in
      olfactory identification ability as well as widely distributed cognitive deficits
      in visual memory, executive functions, attention, and response inhibition. The
      degree of behavioural impairment on motor impulsivity (prolonged response
      inhibition Stop-Signal Reaction Time) strongly correlated with the B-SIT score.
      Our study is the first to indicate a shared OFC pathological neural substrate
      underlying olfactory identification impairment, impulsivity, and OCD. Deficits in
      visual memory, executive functions and attention further indicate that regions
      outside of the orbitofronto-striatal loop may be involved in this disorder. Such
      results may help delineate the clinical complexity of OCD and support more
      targeted investigations and interventions. In this regard, research on the
      potential diagnostic utility of olfactory identification deficits in the
      assessment of OCD would certainly be useful. 

PMID- 23870491
TI  - Startle reactivity in the long-term after severe accidental injury: preliminary
      data.
AB  - An exaggerated startle response is one of the core hyperarousal symptoms of
      posttraumatic stress disorder (PTSD). Heightened startle eye-blink magnitude and
      reduced habituation of this response in PTSD patients have been reported in
      several studies. However, it is unclear whether this is an enduring
      characteristic of individuals vulnerable for PTSD or to which degree trauma
      exposed individuals who do not develop PTSD also show exaggerated startle.
      Thirteen accident survivors with remitted PTSD, 12 trauma controls, and 16 non
      trauma controls were examined. Four measures of startle reactivity were analyzed
      in response to 15 bursts of white noise (95 dB, 50 ms): eye-blink magnitude, eye
      blink onset latency, skin conductance response, and heart rate response. The eye
      blink reflex was measured over the left musculus orbicularis oculi. Reactivity
      and habituation were analyzed using linear mixed models. Remitted PTSD subjects
      did not differ from non-trauma controls regarding any of the startle reactivity
      or habituation measures. Unexpectedly, trauma controls showed larger eye-blink
      magnitude than non-trauma controls. These results suggest that the exaggerated
      startle response disappears after remission from PTSD. Further, they suggest that
      psychologically resilient trauma survivors might show a PTSD-like pattern of
      exaggerated physiological startle even many years after a traumatic event.

PMID- 23870492
TI  - Performance on a computerized shopping task significantly predicts real world
      functioning in persons diagnosed with bipolar disorder.
AB  - Persons diagnosed with bipolar disorder often suffer from cognitive impairments.
      However, little is known concerning how these cognitive deficits impact their
      real world functioning. We developed a computerized real-life activity task,
      where participants are required to shop for a list of grocery store items. Twenty
      one individuals diagnosed with bipolar disorder and 21 matched healthy controls
      were administered the computerized shopping task. Moreover, the patient group was
      assessed with a battery of cognitive tests and clinical scales. Performance on
      the shopping task significantly differentiated patients and healthy controls for
      two variables: Total time to complete the shopping task and Mean time spent to
      consult the shopping list. Moreover, in the patient group, performance on these
      variables from the shopping task correlated significantly with cognitive
      functioning (i.e. processing speed, verbal episodic memory, planning, cognitive
      flexibility, and inhibition) and with clinical variables including duration of
      illness and real world functioning. Finally, variables from the shopping task
      were found to significantly explain 41% of real world functioning of patients
      diagnosed with bipolar disorder. These findings suggest that the shopping task
      provides a good indication of real world functioning and cognitive functioning of
      persons diagnosed with bipolar disorder. 

PMID- 23870493
TI  - Emotion perception and executive functioning predict work status in euthymic
      bipolar disorder.
AB  - Functional recovery, including return to work, in Bipolar Disorder (BD) lags
      behind clinical recovery and may be incomplete when acute mood symptoms have
      subsided. We examined impact of cognition on work status and underemployment in a
      sample of 156 Euthymic-BD and 143 controls (HC) who were divided into working/not
      working groups. Clinical, health, social support, and personality data were
      collected, and eight cognitive factors were derived from a battery of
      neuropsychological tests. The HC groups outperformed the BD groups on seven of
      eight cognitive factors. The working-BD group outperformed the not working-BD
      group on 4 cognitive factors composed of tasks of emotion processing and
      executive functioning including processing speed and set shifting. Emotion
      processing and executive tasks were predictive of BD unemployment, after
      accounting for number of mood episodes. Four cognitive factors accounted for a
      significant amount of the variance in work status among the BD participants.
      Results indicate that patients with BD who are unemployed/unable to work exhibit
      greater difficulties processing emotional information and on executive tasks that
      comprise a set shifting or interference resolution component as compared to those
      who are employed, independent of other factors. These cognitive and affective
      factors are suggested as targets for treatment and/or accommodations. 

PMID- 23870494
TI  - Determinants of government HIV/AIDS financing: a 10-year trend analysis from 125
      low- and middle-income countries.
AB  - BACKGROUND: Trends and predictors of domestic spending from public sources
      provide national authorities and international donors with a better understanding
      of the HIV financing architecture, the fulfillment of governments' commitments
      and potential for long-term sustainability. METHODS: We analyzed government
      financing of HIV using evidence from country reports on domestic spending. Panel
      data from 2000 to 2010 included information from 647 country-years amongst 125
      countries. A random-effects model was used to analyze ten year trends and
      identify independent predictors of public HIV spending. RESULTS: Low- and middle
      income countries spent US$ 2.1 billion from government sources in 2000, growing
      to US$ 6.6 billion in 2010, a three-fold increase. Per capita spending in 2010
      ranged from 5 cents in low-level HIV epidemics in the Middle East to US$ 32 in
      upper-middle income countries with generalized HIV epidemics in Southern Africa.
      The average domestic public spending per capita was US$ 2.55. The analysis found
      that GDP per capita and HIV prevalence are positively associated with increasing
      levels of HIV-spending from public sources; a 10 percent increase in HIV
      prevalence is associated with a 2.5 percent increase in domestic funding for HIV.
      Additionally, a 10 percent increase in GDP per capita is associated with an 11.49
      percent increase in public spending for HIV and these associations were highly
      significant. CONCLUSION: Domestic resources in low- and middle-income countries
      showed a threefold increase between 2000 and 2010 and currently support 50
      percent of the global response with 41 percent coming from sub-Saharan Africa.
      Domestic spending in LMICs was associated with increased economic growth and an
      increased burden of HIV. Sustained increases in funding for HIV from public
      sources were observed in all regions and emphasize the increasing importance of
      government financing.

PMID- 23870495
TI  - Sample size re-assessment leading to a raised sample size does not inflate type I
      error rate under mild conditions.
AB  - BACKGROUND: One major concern with adaptive designs, such as the sample size
      adjustable designs, has been the fear of inflating the type I error rate. In
      (Stat Med 23:1023-1038, 2004) it is however proven that when observations follow
      a normal distribution and the interim result show promise, meaning that the
      conditional power exceeds 50%, type I error rate is protected. This bound and the
      distributional assumptions may seem to impose undesirable restrictions on the use
      of these designs. In (Stat Med 30:3267-3284, 2011) the possibility of going below
      50% is explored and a region that permits an increased sample size without
      inflation is defined in terms of the conditional power at the interim. METHODS: A
      criterion which is implicit in (Stat Med 30:3267-3284, 2011) is derived by
      elementary methods and expressed in terms of the test statistic at the interim to
      simplify practical use. Mathematical and computational details concerning this
      criterion are exhibited. RESULTS: Under very general conditions the type I error
      rate is preserved under sample size adjustable schemes that permit a raise. The
      main result states that for normally distributed observations raising the sample
      size when the result looks promising, where the definition of promising depends
      on the amount of knowledge gathered so far, guarantees the protection of the type
      I error rate. Also, in the many situations where the test statistic approximately
      follows a normal law, the deviation from the main result remains negligible. This
      article provides details regarding the Weibull and binomial distributions and
      indicates how one may approach these distributions within the current setting.
      CONCLUSIONS: There is thus reason to consider such designs more often, since they
      offer a means of adjusting an important design feature at little or no cost in
      terms of error rate.

PMID- 23870497
TI  - Motion detection and compensation in infrared retinal image sequences.
AB  - Infrared image data captured by non-mydriatic digital retinography systems often
      are used in the diagnosis and treatment of the diabetic macular edema (DME).
      Infrared illumination is less aggressive to the patient retina, and retinal
      studies can be carried out without pupil dilation. However, sequences of infrared
      eye fundus images of static scenes, tend to present pixel intensity fluctuations
      in time, and noisy and background illumination changes pose a challenge to most
      motion detection methods proposed in the literature. In this paper, we present a
      retinal motion detection method that is adaptive to background noise and
      illumination changes. Our experimental results indicate that this method is
      suitable for detecting retinal motion in infrared image sequences, and compensate
      the detected motion, which is relevant in retinal laser treatment systems for
      DME. 

PMID- 23870498
TI  - Background level and composition of polybrominated diphenyl ethers (PBDEs) in
      creek and subtidal sediments in a rural area of Korea.
AB  - To study background levels of polybrominated diphenyl ethers (PBDEs) in Korea,
      concentrations of PBDEs were measured for creek and subtidal sediments around
      Goseong Bay. Total concentrations of PBDEs (Sigma19PBDE) in creek sediments
      ranged from 0.18 to 13.95 ng/g dry weight and were about twice those in subtidal
      sediments. PBDE concentrations were about two orders of magnitude lower than
      those reported in industrially active regions of Korea and other countries. BDE
      209 was a major congener, accounting for 79.0% and 78.5% of total PBDEs in creek
      and subtidal sediments, respectively. This is consistent with the high
      consumption of deca-BDE in Korea and the very high octanol-water partition
      coefficient of deca-BDE. The relative compositions of PBDEs in creek and subtidal
      sediments were similar. BDE 209 and Sigma19PBDE had statistically significant
      correlations with total organic carbon, the lower brominated congeners had a poor
      correlation with total organic carbon.

PMID- 23870499
TI  - Monitoring bioavailable phosphorus in lotic systems: a polyphasic approach based
      on cyanobacteria.
AB  - Conventional assays to measure phosphorus in freshwater systems are sometimes not
      sufficient to quantify the actual bioavailable P for aquatic biota since some
      inorganic or organic P species may not be detected by chemical methods, and their
      bioavailability can be affected by a range of environmental factors. This
      situation could lead regulatory agencies to be unable to detect imminent
      ecosystem-degrading phenomena such as cyanobacterial blooms. It could also be an
      obstacle in studying the ecophysiological requirements of freshwater communities.
      P bioavailability in five rivers located in central Spain was analysed by a
      polyphasic approach (combinations of different marker types) based on
      cyanobacteria. This approach included a parallel study with the use of a self
      luminescent P-cyanobacterial bioreporter based on a phosphatase alkaline
      promoter, determination of in situ alkaline phosphatase activities from
      cyanobacteria found at sampling sites, and the characterisation of cyanobacterial
      morphological features related to P bioavailability (hairs, polyphosphate
      granules and calyptras). An inverse relationship was found between values of
      bioavailable P, measured by the bioreporter and phosphatase activities.
      Cyanobacteria from sampling sites with low bioavailable P showed high phosphatase
      activity and vice versa, although some differences in values of this activity
      were observed in different cyanobacteria found at the same place, in relation to
      different growth strategies. Morphological characteristics associated with P
      limitation or P enrichment also varied between sampling locations. Cyanobacteria
      collected from sampling sites with reduced P bioavailability, measured by
      bioreporter and phosphatase activity, had a lower abundance of polyphosphate
      granules; those cyanobacteria capable of developing hairs or calyptras showed a
      greater abundance of these structures. Conversely, polyphosphate granules in
      cyanobacteria increased as P bioavailability increased as measured by the
      bioreporter and phosphatase activity. The study shows that the results of
      genetic, physiological and microscopic analyses based on these methods complement
      each other, implying that combining their findings would provide a more complete
      analysis of the nutrient status of running waters. 

PMID- 23870500
TI  - [Rectal perforation after anorectal manometry without prior known rectal disease:
      an exceptional complication resolved with medical treatment].

PMID- 23870502
TI  - Budget impact analysis on erythropoiesis-stimulating agents use for the
      management of chemotherapy-induced anaemia in Greece.
AB  - BACKGROUND: Chemotherapy-induced anaemia is a common and significant complication
      of chemotherapy treatment. Blood transfusion and administration of Erythropoiesis
      Stimulating Agents (ESAs) either alone or in combination with iron are the most
      widely used therapeutic options. In Greece, ESAs are among the top ten
      therapeutic groups with the highest pharmaceutical expenditure, since they are
      fully reimbursed by social security funds. The objective of the study is to
      determine potential cost savings related with the use of biosimilar over
      originator ESAs for the management of the newly diagnosed chemotherapy-induced
      anemic patients. METHODS: A budget impact analysis has been carried through the
      elaboration of national epidemiological, clinical and economic data.
      Epidemiological data derived from WHO (GLOBOCAN) and the European Cancer Anaemia
      Survey. Clinical data reflect oncology patients' disease management. ESAs
      consumption was based on data from the biggest social security fund (IKA). The
      administration of ESAs under different dosing schemes and time periods has been
      estimated by separating them in originators and biosimilars as well as by
      classifying anaemic patients in responders and non-responders. Cost analysis is
      based on newly diagnosed patients' alternative treatment scenarios. Treatment
      costs and prices are used in 2012 values. The Social Security Funds's perspective
      was undertaken. RESULTS: Based on the annual incidence rates, 2.551 newly
      diagnosed chemotherapy-induced anemic patients are expected to be treated with
      ESAs. Average cost of treatment on originators ESAs for responders is ?2.887 for
      the 15-week ESAs treatment and ?5.019 for non-responders, while on biosimilars
      ?2.623 and ?4.009 respectively. Treatment cost on biosimilars is 10.1% lower than
      originators for responders and 25.2% for non-responders. Budget impact estimates
      show that treating anemic patients with originator ESAs was estimated at
      ?10.084.800 compared to ?8.460.119 when biosimilar ESAs were used, leading to an
      overall 19,20% cost reduction favoring biosimilars. CONCLUSION: In Greece, the
      treatment on biosimilar ESAs seems to be a cost saving option over originators
      for the newly diagnosed chemotherapy-induced anemic patients, since it
      corresponds to 5% of the annual overall consumption and expands patients' access
      to ESAs treatment. Health care decision making should rely on evidence based
      treatments in order to achieve social funds' sustainability in an era of economic
      recession.

PMID- 23870501
TI  - 'In situ simulation' versus 'off site simulation' in obstetric emergencies and
      their effect on knowledge, safety attitudes, team performance, stress, and
      motivation: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Unexpected obstetric emergencies threaten the safety of pregnant
      women. As emergencies are rare, they are difficult to learn. Therefore,
      simulation-based medical education (SBME) seems relevant. In non-systematic
      reviews on SBME, medical simulation has been suggested to be associated with
      improved learner outcomes. However, many questions on how SBME can be optimized
      remain unanswered. One unresolved issue is how 'in situ simulation' (ISS) versus
      'off site simulation' (OSS) impact learning. ISS means simulation-based training
      in the actual patient care unit (in other words, the labor room and operating
      room). OSS means training in facilities away from the actual patient care unit,
      either at a simulation centre or in hospital rooms that have been set up for this
      purpose. METHODS AND DESIGN: The objective of this randomized trial is to study
      the effect of ISS versus OSS on individual learning outcome, safety attitude,
      motivation, stress, and team performance amongst multi-professional obstetric
      anesthesia teams.The trial is a single-centre randomized superiority trial
      including 100 participants. The inclusion criteria were health-care professionals
      employed at the department of obstetrics or anesthesia at Rigshospitalet,
      Copenhagen, who were working on shifts and gave written informed consent.
      Exclusion criteria were managers with staff responsibilities, and staff who were
      actively taking part in preparation of the trial. The same obstetric multi
      professional training was conducted in the two simulation settings. The
      experimental group was exposed to training in the ISS setting, and the control
      group in the OSS setting. The primary outcome is the individual score on a
      knowledge test. Exploratory outcomes are individual scores on a safety attitudes
      questionnaire, a stress inventory, salivary cortisol levels, an intrinsic
      motivation inventory, results from a questionnaire evaluating perceptions of the
      simulation and suggested changes needed in the organization, a team-based score
      on video-assessed team performance and on selected clinical performance.
      DISCUSSION: The perspective is to provide new knowledge on contextual effects of
      different simulation settings. TRIAL REGISTRATION: ClincialTrials.gov
      NCT01792674.

PMID- 23870503
TI  - Can a questionnaire predict vitamin D status in postmenopausal women?
AB  - OBJECTIVE: Our objective was to determine whether a questionnaire can identify
      individuals with vitamin D insufficiency (VDI). DESIGN: Women completed the
      Vitamin D & Sun (VIDSUN) questionnaire and we measured their serum 25
      hydrocyvitamin D (25(OH)D) levels. We assessed the sensitivity and specificity of
      the questionnaire to identify VDI (25(OH)D level <50 nmol/l). SETTING: Clinical
      Research Unit, University of Wisconsin-Madison. SUBJECTS: Postmenopausal women.
      RESULTS: We recruited 609 postmenopausal women with a mean age of 61 (sd 6
      years), of whom 113 (19%) had VDI. Women with VDI were more likely to be black
      (17% v. 2%, P < 0.001), heavier (BMI 33.0 (sd 7) kg/m2 v. 29.0 (sd 7) kg/m2, P <
      0.001) and less likely to tan in the past year (49% v. 72%, P < 0.001), use
      sunscreen (57% v. 72%, P < 0.001) or report sun exposure in the last 3 months.
      They consumed less vitamin D from supplements (2.15 (sd 5.24) MUg/d (86 (sd 210)
      IU/d) v. 4.55 (sd 8.48) MUg/d (188 (sd 344) IU/d), P = 0.003). In logistic
      regression models, black race, BMI, suntan within the past year, sun exposure in
      the past 3 months, sunscreen use and supplemental vitamin D intake were the most
      useful questions to identify VDI. From these six items, a composite score of <=
      2.25 demonstrated >=89% sensitivity but <=35% specificity for VDI. CONCLUSIONS:
      The VIDSUN questionnaire provides an initial tool to identify postmenopausal
      women at high or low risk of VDI. Existing studies suggest that inclusion of
      physical activity and TAG levels might improve the performance of the VIDSUN
      questionnaire.

PMID- 23870504
TI  - Nasopharyngeal melanoma: a rare disorder.

PMID- 23870505
TI  - Congenital vallecular cyst in an infant.

PMID- 23870506
TI  - Vibration induced osteogenic commitment of mesenchymal stem cells is enhanced by
      cytoskeletal remodeling but not fluid shear.
AB  - Consistent across studies in humans, animals and cells, the application of
      vibrations can be anabolic and/or anti-catabolic to bone. The physical mechanisms
      modulating the vibration-induced response have not been identified. Recently, we
      developed an in vitro model in which candidate parameters including acceleration
      magnitude and fluid shear can be controlled independently during vibrations.
      Here, we hypothesized that vibration induced fluid shear does not modulate
      mesenchymal stem cell (MSC) proliferation and mineralization and that cell's
      sensitivity to vibrations can be promoted via actin stress fiber formation.
      Adipose derived human MSCs were subjected to vibration frequencies and
      acceleration magnitudes that induced fluid shear stress ranging from 0.04 Pa to 5
      Pa. Vibrations were applied at magnitudes of 0.15 g, 1g, and 2g using frequencies
      of both 100 Hz and 30 Hz. After 14 d and under low fluid shear conditions
      associated with 100 Hz oscillations, mineralization was greater in all vibrated
      groups than in controls. Greater levels of fluid shear produced by 30 Hz
      vibrations enhanced mineralization only in the 2g group. Over 3d, vibrations led
      to the greatest increase in total cell number with the frequency/acceleration
      combination that induced the smallest level of fluid shear. Acute experiments
      showed that actin remodeling was necessary for early mechanical up-regulation of
      RUNX-2 mRNA levels. During osteogenic differentiation, mechanically induced up
      regulation of actin remodeling genes including Wiskott-Aldrich syndrome (WAS)
      protein, a critical regulator of Arp2/3 complex, was related to the magnitude of
      the applied acceleration but not to fluid shear. These data demonstrate that
      fluid shear does not regulate vibration induced proliferation and mineralization
      and that cytoskeletal remodeling activity may play a role in MSC
      mechanosensitivity.

PMID- 23870507
TI  - The effect of strain rate on the failure stress and toughness of bone of
      different mineral densities.
AB  - The risk of low energy fracture of the bone increases with age and osteoporosis.
      This paper investigates the effect of strain rate and mineral level on the peak
      stress and toughness of whole ovine bones. 40 fresh ovine femurs were subjected
      to 3-point bending at high (17.14s(-1)) and low (8.56 * 10(-3)s(-1)) strain rates
      with or without a controlled amount of demineralisation. Mineral removal was
      achieved by ultrasonically assisted exposure in Ethylene diamine tetra-acetic
      acid (EDTA). The ultimate stress for whole bones of normal mineral content was
      200 MPa at the high rate of strain and 149 MPa at the low rate of strain. With
      changes in bone mineral levels such as may occur in osteomalacia and
      osteoporosis, the change in toughness varied at different strain rates; a mean
      value of 3.7 +/- 1.4 MJ/m(3) was obtained for the toughness of normal quality
      whole bone tested at slow loading rate and a reduction of approximately 25% was
      observed in the demineralised whole bone specimens at the slow loading rate (mean
      2.8 +/- 0.9 MJ/m(3)). When tested at the high loading rate there was a negligible
      difference in the toughness between the two (2.0 +/- 0.6 MJ/m(3)) mineral levels.
      This indicated that there was a strain rate dependant effect for the mineral
      density, and that the removal of mineral alone did not explain all of the
      reduction in mechanical properties that occur with age or disease. Thus, the
      reduction in mechanical properties at high strain rates was likely to be due to
      other phenomena such as increased porosity or reduced collagen quality, rather
      than loss of mineral. With decreasing mineral levels, as measured by DEXA in
      clinical practice, the increased fracture risk is dependent on the velocity of
      the impact. Thus the estimates of increased fracture risk given clinically for a
      lower DEXA value should be different for high and low energy injuries.

PMID- 23870508
TI  - Understanding the role of ETS-mediated gene regulation in complex biological
      processes.
AB  - Ets factors are members of one of the largest families of evolutionarily
      conserved transcription factors, regulating critical functions in normal cell
      homeostasis, which when perturbed contribute to tumor progression. The well
      documented alterations in ETS factor expression and function during cancer
      progression result in pleiotropic effects manifested by the downstream effect on
      their target genes. Multiple ETS factors bind to the same regulatory sites
      present on target genes, suggesting redundant or competitive functions. The anti-
      and prometastatic signatures obtained by examining specific ETS regulatory
      networks will significantly improve our ability to accurately predict tumor
      progression and advance our understanding of gene regulation in cancer.
      Coordination of multiple ETS gene functions also mediates interactions between
      tumor and stromal cells and thus contributes to the cancer phenotype. As such,
      these new insights may provide a novel view of the ETS gene family as well as a
      focal point for studying the complex biological control involved in tumor
      progression. One of the goals of molecular biology is to elucidate the mechanisms
      that contribute to the development and progression of cancer. Such an
      understanding of the molecular basis of cancer will provide new possibilities
      for: (1) earlier detection, as well as better diagnosis and staging of disease;
      (2) detection of minimal residual disease recurrences and evaluation of response
      to therapy; (3) prevention; and (4) novel treatment strategies. Increased
      understanding of ETS-regulated biological pathways will directly impact these
      areas. 

PMID- 23870509
TI  - Advances in understanding the coupling of DNA base modifying enzymes to processes
      involving base excision repair.
AB  - This chapter describes some of the recent, exciting developments that have
      characterized and connected processes that modify DNA bases with DNA repair
      pathways. It begins with AID/APOBEC or TET family members that covalently modify
      bases within DNA. The modified bases, such as uracil or 5-formylcytosine, are
      then excised by DNA glycosylases including UNG or TDG to initiate base excision
      repair (BER). BER is known to preserve genome integrity by removing damaged
      bases. The newer studies underscore the necessity of BER following enzymes that
      deliberately damage DNA. This includes the role of BER in antibody
      diversification and more recently, its requirement for demethylation of 5
      methylcytosine in mammalian cells. The recent advances have shed light on
      mechanisms of DNA demethylation, and have raised many more questions. The
      potential hazards of these processes have also been revealed. Dysregulation of
      the activity of base modifying enzymes, and resolution by unfaithful or corrupt
      means can be a driver of genome instability and tumorigenesis. The understanding
      of both DNA and histone methylation and demethylation is now revealing the true
      extent to which epigenetics influence normal development and cancer, an abnormal
      development. 

PMID- 23870511
TI  - Mitochondrial alterations during carcinogenesis: a review of metabolic
      transformation and targets for anticancer treatments.
AB  - Mitochondria play important roles in multiple cellular processes including energy
      metabolism, cell death, and aging. Regulated energy production and utilization
      are critical in maintaining energy homeostasis in normal cells and functional
      organs. However, mitochondria go through a series of morphological and functional
      alterations during carcinogenesis. The metabolic profile in transformed cells is
      altered to accommodate their fast proliferation, confer resistance to cell death,
      or facilitate metastasis. These transformations also provide targets for
      anticancer treatment at different levels. In this review, we discuss the major
      modifications in cell metabolism during carcinogenesis, including energy
      metabolism, apoptotic and autophagic cell death, adaptation of tumor
      microenvironment, and metastasis. We also summarize some of the main metabolic
      targets for treatments. 

PMID- 23870512
TI  - Human polynucleotide phosphorylase (hPNPaseold-35): should I eat you or not--that
      is the question?
AB  - RNA degradation plays a fundamental role in maintaining cellular homeostasis
      whether it occurs as a surveillance mechanism eliminating aberrant mRNAs or
      during RNA processing to generate mature transcripts. 3'-5' exoribonucleases are
      essential mediators of RNA decay pathways, and one such evolutionarily conserved
      enzyme is polynucleotide phosphorylase (PNPase). The human homologue of this
      fascinating enzymatic protein (hPNPaseold-35) was cloned a decade ago in the
      context of terminal differentiation and senescence through a novel "overlapping
      pathway screening" approach. Since then, significant insights have been garnered
      about this exoribonuclease and its repertoire of expanding functions. The
      objective of this review is to provide an up-to-date perspective of the recent
      discoveries made relating to hPNPaseold-35 and the impact they continue to have
      on our comprehension of its expanding and diverse array of functions.

PMID- 23870510
TI  - Role of oxidative stress and the microenvironment in breast cancer development
      and progression.
AB  - Breast cancer is a highly complex tissue composed of neoplastic and stromal
      cells. Carcinoma-associated fibroblasts (CAFs) are commonly found in the cancer
      stroma, where they promote tumor growth and enhance vascularity in the
      microenvironment. Upon exposure to oxidative stress, fibroblasts undergo
      activation to become myofibroblasts. These cells are highly mobile and
      contractile and often express numerous mesenchymal markers. CAF activation is
      irreversible, making them incapable of being removed by nemosis. In breast
      cancer, almost 80% of stromal fibroblasts acquire an activated phenotype that
      manifests by secretion of elevated levels of growth factors, cytokines, and
      metalloproteinases. They also produce hydrogen peroxide, which induces the
      generation of subsequent sets of activated fibroblasts and tumorigenic
      alterations in epithelial cells. While under oxidative stress, the tumor stroma
      releases high energy nutrients that fuel cancer cells and facilitate their growth
      and survival. This review describes how breast cancer progression is dependent
      upon oxidative stress activated stroma and proposes potential new therapeutic
      avenues. 

PMID- 23870513
TI  - FOXM1 (Forkhead box M1) in tumorigenesis: overexpression in human cancer,
      implication in tumorigenesis, oncogenic functions, tumor-suppressive properties,
      and target of anticancer therapy.
AB  - FOXM1 (Forkhead box M1) is a typical proliferation-associated transcription
      factor and is also intimately involved in tumorigenesis. FOXM1 stimulates cell
      proliferation and cell cycle progression by promoting the entry into S-phase and
      M-phase. Additionally, FOXM1 is required for proper execution of mitosis. In
      accordance with its role in stimulation of cell proliferation, FOXM1 exhibits a
      proliferation-specific expression pattern and its expression is regulated by
      proliferation and anti-proliferation signals as well as by proto-oncoproteins and
      tumor suppressors. Since these factors are often mutated, overexpressed, or lost
      in human cancer, the normal control of the foxm1 expression by them provides the
      basis for deregulated FOXM1 expression in tumors. Accordingly, FOXM1 is
      overexpressed in many types of human cancer. FOXM1 is intimately involved in
      tumorigenesis, because it contributes to oncogenic transformation and
      participates in tumor initiation, growth, and progression, including positive
      effects on angiogenesis, migration, invasion, epithelial-mesenchymal transition,
      metastasis, recruitment of tumor-associated macrophages, tumor-associated lung
      inflammation, self-renewal capacity of cancer cells, prevention of premature
      cellular senescence, and chemotherapeutic drug resistance. However, in the
      context of urethane-induced lung tumorigenesis, FOXM1 has an unexpected tumor
      suppressor role in endothelial cells because it limits pulmonary inflammation and
      canonical Wnt signaling in epithelial lung cells, thereby restricting
      carcinogenesis. Accordingly, FOXM1 plays a role in homologous recombination
      repair of DNA double-strand breaks and maintenance of genomic stability, that is,
      prevention of polyploidy and aneuploidy. The implication of FOXM1 in
      tumorigenesis makes it an attractive target for anticancer therapy, and several
      antitumor drugs have been reported to decrease FOXM1 expression. 

PMID- 23870515
TI  - Anti-malarial prescription practices among outpatients with laboratory-confirmed
      malaria in the setting of a health facility-based sentinel site surveillance
      system in Uganda.
AB  - BACKGROUND: Most African countries have adopted artemisinin-based combination
      therapy (ACT) as the first-line treatment for uncomplicated malaria. The World
      Health Organization now recommends limiting anti-malarial treatment to those with
      a positive malaria test result. Limited data exist on how these policies have
      affected ACT prescription practices. METHODS: Data were collected from all
      outpatients presenting to six public health facilities in Uganda as part of a
      sentinel site malaria surveillance programme. Training in case management,
      encouragement of laboratory-based diagnosis of malaria, and regular feedback were
      provided. Data for this report include patients with laboratory confirmed malaria
      who were prescribed anti-malarial therapy over a two-year period. Patient visits
      were analysed in two groups: those considered ACT candidates (defined as
      uncomplicated malaria with no referral for admission in patients >= 4 months of
      age and >= 5 kg in weight) and those who may not have been ACT candidates.
      Associations between variables of interest and failure to prescribe ACT to
      patients who were ACT candidates were estimated using multivariable logistic
      regression. RESULTS: A total of 51,355 patient visits were included in the
      analysis and 46,265 (90.1%) were classified as ACT candidates. In the ACT
      candidate group, 94.5% were correctly prescribed ACT. Artemether-lumefantrine
      made up 97.3% of ACT prescribed. There were significant differences across the
      sites in the proportion of patients for whom there was a failure to prescribe
      ACT, ranging from 3.0-9.3%. Young children and woman of childbearing age had
      higher odds of failure to receive an ACT prescription. Among patients who may not
      have been ACT candidates, the proportion prescribed quinine versus ACT differed
      based on if the patient had severe malaria or was referred for admission (93.4%
      vs 6.5%) or was below age or weight cutoffs for ACT (41.4% vs 57.2%).
      CONCLUSIONS: High rates of compliance with recommended ACT use can be achieved in
      resource-limited settings. The unique health facility-based malaria surveillance
      system operating at these clinical sites may provide a framework for improving
      appropriate ACT use at other sites in sub-Saharan Africa.

PMID- 23870517
TI  - Ensuring fair allocation of organs.

PMID- 23870516
TI  - Bone: the final frontier for Staphylococcus aureus penetration in chronic
      rhinosinusitis.
AB  - The superantigenic properties of Staphylococcus aureus have been implicated in
      increasing the inflammatory process in airway diseases. Local formation of IgE
      antibodies against staphylococcal enterotoxins by secondary lymphoid tissue in
      nasal polyps has been demonstrated. Staphylococcus aureus is known to colonize
      the nasal mucosa, and has been found invading the nasal submucosa and
      intracellularly. OBJECTIVE: To evaluate the limits of Staphylococcus aureus
      invasion in the upper airway. MATERIAL AND METHODS: Inferior turbinate samples
      from 3 patients without sinus disease, 6 ethmoid samples from patients with
      chronic rhinosinusitis with nasal polyposis, and 6 ethmoid samples from patients
      with chronic rhinosinusitis without nasal polyposis were studied. A fluorescein
      labeled PNA probe against Staphylococcus aureus was used to test for the presence
      of the bacterium in bone (after decalcification) and mucosa. RESULTS: We found
      Staphylococcus aureus invading the nasal submucosa in patients with nasal
      polyposis, but no cases of Staphylococcus aureus positivity in bone. In
      conclusion, we cannot support the hypothesis of nasal bone as a reservoir for
      Staphylococcus aureus, releasing massive amounts of staphylococcal enterotoxins
      and eliciting an inflammatory reaction, as occurs with the nasal mucosa.

PMID- 23870518
TI  - Ireland's abortion law: a start but not enough.

PMID- 23870519
TI  - Tobacco control: when economics trumps health.

PMID- 23870520
TI  - Inequality and mental disorders: opportunities for action.

PMID- 23870523
TI  - Ruslan Medzhitov: creative and conceptual immunologist.

PMID- 23870524
TI  - Pleurodesis for primary spontaneous pneumothorax - authors' reply.

PMID- 23870514
TI  - Therapeutic cancer vaccines: past, present, and future.
AB  - Therapeutic vaccines represent a viable option for active immunotherapy of
      cancers that aim to treat late stage disease by using a patient's own immune
      system. The promising results from clinical trials recently led to the approval
      of the first therapeutic cancer vaccine by the U.S. Food and Drug Administration.
      This major breakthrough not only provides a new treatment modality for cancer
      management but also paves the way for rationally designing and optimizing future
      vaccines with improved anticancer efficacy. Numerous vaccine strategies are
      currently being evaluated both preclinically and clinically. This review
      discusses therapeutic cancer vaccines from diverse platforms or targets as well
      as the preclinical and clinical studies employing these therapeutic vaccines. We
      also consider tumor-induced immune suppression that hinders the potency of
      therapeutic vaccines, and potential strategies to counteract these mechanisms for
      generating more robust and durable antitumor immune responses. 

PMID- 23870525
TI  - Pleurodesis for primary spontaneous pneumothorax.

PMID- 23870526
TI  - Pleurodesis for primary spontaneous pneumothorax.

PMID- 23870527
TI  - Measuring universities' commitments to global health.

PMID- 23870528
TI  - The CRASH-2 trial was not about global scientific supremacy.

PMID- 23870529
TI  - Reducing trauma deaths in the UK.

PMID- 23870530
TI  - Granulomatous tattoo reaction in a young man.

PMID- 23870531
TI  - Heme oxygenase-1 mediated memorial and revivable protective effect of ischemic
      preconditioning on brain injury.
AB  - AIMS: Ischemic preconditioning (IPC) has short-term benefits for stroke patients.
      However, if IPC protective effect is memorial and the role of the intracellular
      protective protein heme oxygenase-1 (HO-1) is not known. METHODS: Ischemic
      preconditioning and the corresponding sham control were achieved by blocking the
      blood flow of the left internal carotid artery for 20 min and 2 second,
      respectively, in rats. Both IPC and sham-operated animals were divided into three
      groups and treated with PBS, the HO-1 inducer hemin, and the HO-1 inhibitor Znpp.
      Three weeks after IPC, brain ischemia-reperfusion injury was achieved by left
      middle cerebral artery obstruction for 45 min followed by 24-h reperfusion.
      RESULTS: 2,3,5-triphenyltetrazolium chloride staining and neurological
      dysfunction scoring showed IPC significantly reduced brain infarct area and
      improved neurological function occurred 3 weeks after IPC. Hemin treatment
      promoted whereas ZnPP blocked the benefits of IPC. Immunohistochemical analysis
      and Western blotting showed that the expression of HO-1 was higher in the border
      zone than in the necrotic core zone. The memorial IPC protection is independent
      of adenosine receptor A1R and A2aR expressions. CONCLUSIONS: We found for the
      first time that the protective effect of IPC can be remembered to protect brain
      injury occurred after acute response disappear. The results indicate that
      interventional treatment can achieve protective effect for future cerebral injury
      not only through interventional treatment itself but also through the memorial
      and revivable IPC, eliminating the concern that temporary ischemia caused by
      interventional treatment may leave harmful effect in the brain.

PMID- 23870532
TI  - Web-based cognitive bias modification for problem drinkers: protocol of a
      randomised controlled trial with a 2x2x2 factorial design.
AB  - BACKGROUND: The automatic tendency to attend to, positively evaluate and approach
      alcohol related stimuli has been found to play a causal role in problematic
      alcohol use and can be retrained by computerised Cognitive Bias Modification
      (CBM). In spite of CBMs potential as an internet intervention, little is known
      about the efficacy of web-based CBM. The study described in this protocol will
      test the effectiveness of web-based CBM in a double blind randomised controlled
      trial with a 2 (attention bias retraining: real versus placebo) x 2 (alcohol/no
      go training: real versus placebo) x 2 (approach bias retraining: real versus
      placebo) factorial design. METHODS/DESIGN: The effectiveness of 12 sessions of
      CBM will be examined among problem drinkers aged 18-65 who are randomly assigned
      to one of the eight CBM conditions, after completing two modules of a validated
      cognitive behavioural intervention, DrinkingLess. The primary outcome measure is
      the change in alcohol use. It is expected that, for each of the CBM
      interventions, participants in the real CBM conditions will show a greater
      decrease in alcohol use than participants in the placebo conditions. Secondary
      outcome measures include the percentage of participants drinking within the
      limits for sensible drinking. Possible mediating (change in automatic biases) and
      moderating (working memory, inhibition) factors will be examined, as will the
      comparative cost-effectiveness of the various CBM strategies. DISCUSSION: This
      study will be the first to test the relative efficacy of various web-based CBM
      strategies in problem drinkers. If proven effective, CBM could be implemented as
      a low-cost, low-threshold adjuvant to CBT-based online interventions for problem
      drinkers. TRIAL REGISTRATION: Netherlands Trial register: NTR3875.

PMID- 23870533
TI  - Subversion of trafficking, apoptosis, and innate immunity by type III secretion
      system effectors.
AB  - Injection of effector proteins by a type III secretion system (T3SS) is a common
      infection strategy employed by many important human pathogens, including enteric
      Escherichia coli, Salmonella, Yersinia, and Shigella, to subvert cell signaling
      and host responses. In recent years, great advances have been made in
      understanding how the T3SS effectors function and execute the diverse infection
      strategies employed by these pathogens. In this review, we focus on effectors
      that subvert signaling pathways that impact on endosomal trafficking, cell
      survival, and innate immunity, particularly phagocytosis, nuclear factor-kappaB
      (NF-kappaB), and mitogen-activated protein (MAP) kinase pathways and the
      inflammasome. 

PMID- 23870534
TI  - Minocycline influences the anti-inflammatory interleukins and enhances the
      effectiveness of morphine under mice diabetic neuropathy.
AB  - A single streptozotocin (STZ) injection in mice can induce significant
      neuropathic pain along with an increase in plasma glucose levels and a decrease
      in body weight. Seven days after the administration of STZ, an upregulation of
      C1q-positive cells was observed. Additionally, interleukins (IL-1beta, IL-3, IL
      4, IL-6, IL-9, IL12p70, IL-17); proteins of the tumor necrosis factor (TNF)
      family, e.g., IFNgamma and sTNF RII, were upregulated. Chronic administration of
      minocycline increases antinociceptive factors (IL-1alpha, IL-2, IL-10, sTNFRII)
      in diabetic mice. Minocycline also reduces the occurrence of neuropathic pain and
      significantly potentiates the antiallodynic and antihyperalgesic effects of
      morphine.

PMID- 23870535
TI  - Serum and cerebrospinal fluid light neurofilaments and antibodies against them in
      clinically isolated syndrome and multiple sclerosis.
AB  - A release of light neurofilament subunits (NFL) into cerebrospinal fluid (CSF)
      and serum in multiple sclerosis (MS) may induce an immune response. We examined
      CSF and serum NFL levels and IgG antibodies against NFL in 19 patients with a
      clinically isolated syndrome (CIS) early converted into MS, 20 CIS-non
      converters, 23 MS patients and 32 controls. CSF NFL levels were significantly
      higher in all patient groups. The highest CSF or intrathecally (IT) synthesized
      anti-NFL antibodies and CSF/serum ratios of anti-NFL antibodies were observed in
      CIS-converters. CSF NFL and CSF or IT anti-NFL antibodies could be surrogate
      biomarkers of axonal injury in early MS.

PMID- 23870536
TI  - Melatonin protects mast cells against cytotoxicity mediated by chemical stimuli
      PMACI: possible clinical use.
AB  - Melatonin has documented cytoprotective effects on a wide variety of immune
      cells. The mechanism of action on mast cells (RBL-2H3) still remains in the dark.
      We found that melatonin significantly attenuated phorbol 12-myristate 13-acetate
      plus calcium ionophore A23187 (PMACI)-induced cytotoxicity in a concentration and
      time-dependent manner. It appears that the effect of melatonin on mast cells is
      two-fold: dependent (MT1 and MT2) and independent membrane receptors. In
      conclusion, melatonin treatment reduced the cytotoxicity, mediated by PMACI, and
      could provide a useful therapeutic option in processes where an excessive
      activation of mast cells occurs.

PMID- 23870537
TI  - How QOF is shaping primary care review consultations: a longitudinal qualitative
      study.
AB  - BACKGROUND: Long-term conditions (LTCs) are increasingly important determinants
      of quality of life and healthcare costs in populations worldwide. The Chronic
      Care Model and the NHS and Social Care Long Term Conditions Model highlight the
      use of consultations where patients are invited to attend a consultation with a
      primary care clinician (practice nurse or GP) to complete a review of the
      management of the LTC. We report a qualitative study in which we focus on the
      ways in which QOF (Quality and Outcomes Framework) shapes routine review
      consultations, and highlight the tensions exposed between patient-centred
      consulting and QOF-informed LTC management. METHODS: A longitudinal qualitative
      study. We audio-recorded consultations of primary care practitioners with
      patients with LTCs. We then interviewed both patients and practitioners using
      tape-assisted recall. Patient participants were followed for three months during
      which the research team made weekly contact and invited them to complete weekly
      logs about their health service use. A second interview at three months was
      conducted with patients. Analysis of the data sets used an integrative framework
      approach. RESULTS: Practitioners view consultations as a means of 'surveillance'
      of patients. Patients present themselves, often passively, to the practitioner
      for scrutiny, but leave the consultation with unmet biomedical, informational and
      emotional needs. Patients perceived review consultations as insignificant and
      irrelevant to the daily management of their LTC and future healthcare needs. Two
      deviant cases, where the requirements of the 'review' were subsumed to meet the
      patient's needs, focused on cancer and bereavement. CONCLUSIONS: Routine review
      consultations in primary care focus on the biomedical agenda set by QOF where the
      practitioner is the expert, and the patient agenda unheard. Review consultations
      shape patients' expectations of future care and socialize patients into becoming
      passive subjects of 'surveillance'. Patient needs outside the narrow protocol of
      the review are made invisible by the process of review except in extreme cases
      such as anticipating death and bereavement. We suggest how these constraints
      might be overcome.

PMID- 23870538
TI  - Positive rate and score discrepancies of myeloperoxidase staining at different
      temperatures.
AB  - Myeloperoxidase (MPO) is a strong marker of acute myeloid leukemia. The aim of
      this study was to compare MPO staining at different temperatures. Four bone
      marrow aspirate smears of each case were incubated with MPO staining solution at
      4 degrees C, 20 degrees C, 37 degrees C and 50 degrees C, respectively. 30
      patients with score <150 at 50 degrees C were group A; 26 patients with score
      >=150 at 50 degrees C were group B. The results showed that at 4 degrees C, MPO
      positive blasts in two cases of group A were both 2%; at 50 degrees C, MPO
      positive blasts in the two cases were 42% and 30%, respectively. At 4 degrees C,
      20 degrees C, 37 degrees C and 50 degrees C, the mean positive rates of group A
      were 30.6%, 42.2%, 53.7% and 56.5%, respectively (P<0.001); their mean scores
      were 52.2, 75.9, 99.5 and 105.3, respectively (P<0.001); the mean positive rates
      of group B were 84.1%, 88.7%, 92.3% and 93.7%, respectively (P<0.001); their mean
      scores were 199.5, 224.7, 243.5 and 244.5, respectively (P<0.001). From this
      study we can conclude that most MPO staining is effective over a wide temperature
      range with the highest positive rate at 50 degrees C. MPO staining intensity at
      low temperature is much lower and may be false negative. Good MPO staining is
      achieved at 37 degrees C. 

PMID- 23870540
TI  - Effectiveness of a web-based intervention for injured claimants: a randomized
      controlled trial.
AB  - BACKGROUND: There is considerable evidence showing that injured people who are
      involved in a compensation process show poorer physical and mental recovery than
      those with similar injuries who are not involved in a compensation process. One
      explanation for this reduced recovery is that the legal process and the
      associated retraumatization are very stressful for the claimant. The aim of this
      study was to empower injured claimants in order to facilitate recovery. METHODS:
      Participants were recruited by three Dutch claims settlement offices. The
      participants had all been injured in a traffic crash and were involved in a
      compensation process. The study design was a randomized controlled trial. An
      intervention website was developed with (1) information about the compensation
      process, and (2) an evidence-based, therapist-assisted problem-solving course.
      The control website contained a few links to already existing websites. Outcome
      measures were empowerment, self-efficacy, health status (including depression,
      anxiety, and somatic symptoms), perceived fairness, ability to work, claims
      knowledge and extent of burden. The outcomes were self-reported through online
      questionnaires and were measured four times: at baseline, and at 3, 6, and 12
      months. RESULTS: In total, 176 participants completed the baseline questionnaire
      after which they were randomized into either the intervention group (n=88) or the
      control group (n=88). During the study, 35 participants (20%) dropped out. The
      intervention website was used by 55 participants (63%). The health outcomes of
      the intervention group were no different to those of the control group. However,
      the intervention group considered the received compensation to be fairer
      (P<0.01). The subgroup analysis of intervention users versus nonusers did not
      reveal significant results. The intervention website was evaluated positively.
      CONCLUSIONS: Although the web-based intervention was not used enough to improve
      the health of injured claimants in compensation processes, it increased the
      perceived fairness of the compensation amount. TRIAL REGISTRATION: Netherlands
      Trial Register NTR2360.

PMID- 23870541
TI  - Proteomics-based identification of novel proteins in temporal tendons of patients
      with masticatory muscle tendon--aponeurosis hyperplasia.
AB  - Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a new disease
      associated with limited mouth opening that is often misdiagnosed as a
      temporomandibular disorder; subsequently, patients are mistakenly treated with
      irreversible operations. Due to the poor presentation and characterization of
      symptoms, the underlying pathological conditions remain unclear. We have
      previously conducted a proteomic analysis of tendons derived from one MMTAH
      subject and one facial deformity subject using two-dimensional fluorescence
      difference gel electrophoresis and liquid chromatography coupled with tandem mass
      spectrometry. However, the results were obtained for only one subject. The aim of
      the present study was to confirm the expression of specific molecules in tendon
      tissues from multiple subjects with MMTAH by applying two-dimensional
      polyacrylamide gel electrophoresis with matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry. Of the 19 proteins identified in
      tendons from both MMTAH and facial deformity patients, fibrinogen fragment D and
      beta-crystallin A4 were up-regulated, whereas myosin light chain 4 was down
      regulated in MMTAH. We also found fibrinogen to be expressed robustly in tendon
      tissues of MMTAH patients. Our data provide the possibility that the distinctive
      expression of these novel proteins is associated with the pathology of MMTAH. 

PMID- 23870542
TI  - Soft and hard tissue changes in skeletal Class III patients treated with double
      jaw orthognathic surgery-maxillary advancement and mandibular setback.
AB  - The soft tissues of the facial profile may change after skeletal movement in
      orthognathic surgery. The aim of this study was to evaluate and compare the
      differences and correlation between hard and soft tissues after double-jaw
      surgery in skeletal Class III subjects. Radiographs from the following time
      points were assessed using Dolphin Imaging software: preoperative (T0), 2-4
      months postoperative (T1), and 6-12 months postoperative (T2). Eleven hard and
      soft tissue points of the facial profile were evaluated. The Student's t-test was
      used to assess the significance of differences between the time intervals;
      Pearson's correlation coefficient was used to assess the significance of
      correlation existing between these points; significance was set at P<0.05. In the
      sample of 58 subjects, the correlation between hard and soft tissues in the
      mandible was greater than in the maxilla. Similarly, the correlations only
      between hard tissues and only between soft tissues presented a greater
      correlation in the mandible. The results are similar to those found in studies on
      single-jaw surgery for both the maxilla and the mandible. The influence of
      movements in hard tissues was restricted to the soft tissues of the same jaw,
      although there were exceptions. 

PMID- 23870544
TI  - Zeolite imidazolate framework-8 as sorbent for on-line solid-phase extraction
      coupled with high-performance liquid chromatography for the determination of
      tetracyclines in water and milk samples.
AB  - Zeolite imidazolate framework-8 (ZIF-8) was used as the novel sorbent for on-line
      solid-phase extraction coupled with high-performance liquid chromatography (HPLC)
      for the determination of oxytetracycline (OTC), tetracycline (TC) and
      chlorotetracycline (CTC) in water and milk samples. 390mg of ZIF-8 was packed
      into a stainless steel column (3cm long*4.6mm i.d.) which was mounted on the HPLC
      injector valve to replace the sample loop. On-line solid-phase extraction of OTC,
      TC and CTC was achieved by loading sample solution at a flow rate of 3.0mLmin(-1)
      for 10min with the aid of a flow-injection system. The extracted analytes were
      subsequently eluted into a C18 analytical column (25cm long*4.6mm i.d.) for HPLC
      separation under isocratic condition with a mobile phase (10% MeOH-20% ACN-70%
      0.02molL(-1) oxalic acid solution) at a flow rate of 1.0mLmin(-1). Under
      optimized conditions, the developed method gave the enhancement factors of 35-61,
      the linearity range of 5-1000MUgL(-1), the detection limits of 1.5-8.0MUgL(-1),
      quantification limits of 5.0-26.7MUgL(-1), uncertainties of 0.9-1.1MUgL(-1), and
      the sample throughput of 4 samples h(-1). The recoveries of OTC, TC and CTC at
      50MUgL(-1) in water and milk samples ranged from 70.3% to 107.4%. 

PMID- 23870543
TI  - Preparation, characterization and application of organic-inorganic hybrid
      caffeine imprinted monolith.
AB  - The present work aims to synthesize an organic-inorganic hybrid caffeine
      imprinted monolith using one-step method. The synthesis conditions such as the
      type of inorganic precursor and porogenic solvent, the molar ratios of the
      monomer and cross-linker, the volume ratio of the inorganic alcoholysate and
      organic part were optimized. The morphology of the monolith was studied by
      scanning electron microscopy and Fourier transform infrared spectra. The
      imprinted factor of the monolith for caffeine reached 3.02. A simple, rapid and
      sensitive method for the determination of caffeine in children's milk using the
      organic-inorganic hybrid caffeine imprinted polymer monolith microextraction
      combined with high-performance liquid chromatography-photodiodes array detector
      was developed. Several parameters affecting the sample pretreatment were
      investigated, including the type, flow rate and volume of eluent, the flow rate
      and volume of sample solution. The assay exhibited a linear dynamic range of 8
      500MUgL(-1) with the correlation coefficient above 0.9987. Lower limits of
      detection (LOD, at S/N=3) and quantification (LOQ, at S/N=10) in children's milk
      samples were 2.7 and 8MUgL(-1). Recoveries of caffeine from spiked children's
      milk ranged from 85 to 104% with relative standard deviations of less than 8.9%. 

PMID- 23870545
TI  - Packed multi-channels for parallel chromatographic separations in microchips.
AB  - Here we report on a simple method to fabricate microfluidic chip incorporating
      multi-channel systems packed by conventional chromatographic particles without
      the use of frits. The retaining effectivities of different bottlenecks created in
      the channels were studied. For the parallel multi-channel chromatographic
      separations several channel patterns were designed. The obtained multipackings
      were applied for parallel separations of dyes. The implementation of several
      chromatographic separation units in microscopic size makes possible faster and
      high throughput separations. 

PMID- 23870546
TI  - Multi-dimension microchip-capillary electrophoresis device for determination of
      functional proteins in infant milk formula.
AB  - To improve resolution of important minor proteins and eliminate time-consuming
      precipitation of major protein with associated analyte co-precipitation risk, a
      multi-dimension strategy is adopted in the 2D microchip-CE device to isolate
      major proteins on-chip, enrich minor proteins in capillary before their
      separation in CE for UV quantitation. A standard fluorescent protein mixture
      containing FITC-BSA, myoglobin and cytochrome as specific pI markers has prepared
      to demonstrate capability of the device to fractionate minor proteins by IEF. The
      results using a standard protein mixture with profile resembling infant milk
      formula show a complete isolation of high abundance proteins by a 2-min 1D IEF
      run. The subsequent t-ITP/CZE run by on-chip high voltage switching delivers a
      high stacking ratio, realizing 60 folds enrichment of isolated protein fractions.
      All five important functional proteins (LF, IgG, alpha-LA, beta-LgA and beta-LgB)
      known to fortify infant milk formula are isolated and determined using two
      consecutive t-ITP-CZE runs within a 18-min total assay time, a significant saving
      compared to several hours conventional pretreatment. For a 100g infant milk
      formula sample, working ranges of 20-8000mg, repeatability 3.8-5.3% and detection
      limits 2.3-10mg have been achieved to meet government regulations. Method
      reliability is established by 100% recoveries and agreeable results within
      expected ranges and labeled values. The capability of the device for field
      operation, rapid assay with quick results, label-free universal detection, simple
      operation by aqueous dissolution before injection, and the demanding matching in
      2D separation based on isolated fractions at specified pI ranges, closely matched
      migration time and baseline-resolved peak shape makes the device a general tool
      to detect unknown proteins and determine known minor proteins in protein-rich
      samples with interfering constituents. 

PMID- 23870547
TI  - Use of on-line stop-flow heart-cutting two-dimensional high performance liquid
      chromatography for simultaneous determination of 12 major constituents in tartary
      buckwheat (Fagopyrum tataricum Gaertn).
AB  - The use of two-dimensional liquid chromatography (2D-LC) for quantification
      studies presents challenges with respect to repeatability, precision, and
      robustness. The present study used an on-line stop-flow heart-cutting 2D-LC
      system to determine 12 chemical constituents in tartary buckwheat. A combination
      of various stationary phases was developed and bridged using two switch valves as
      the interface. Hydrophilic interaction chromatography was chosen for separation
      in the first dimension ((1)D), and mixed mode stationary phases (an amide polar
      embedded phase and alkyl-phenyl phase) were used in parallel for separation in
      the second dimension ((2)D). The mobile phase comprised acetonitrile and water
      containing 0.03% aqueous phosphoric acid. The sample was separated into two
      fractions on the (1)D column (HILIC-10 column) using 5% acetonitrile. One
      fraction, mainly comprising flavonoids, was directly eluted onto the head of (2)D
      column (Polar Advantage II column) and further separated using a linear gradient
      of 11-23% acetonitrile. The second fraction, containing phenylpropanoid
      glycosides, was trapped on the (1)D column. This retained fraction was back
      flushed onto the (2)D column (Phenyl-1 column) and separated using a linear
      gradient of 35-43% acetonitrile. An on-line stop-flow heart-cutting 2D-LC system
      was successfully developed with column switching and back-flush. This 2D-LC
      system was validated and was able to simultaneously determine 12 major components
      in tartary buckwheat: seven flavonoids, four phenylpropanoid glycosides, and N
      trans-feruloyltyramine. The system showed good performance with respect to
      linearity (r>0.996), repeatability (RSD, relative standard deviation<3.4%), intra
      day and inter-day precision (RSD<4.6%), recovery (91.2-108%), limit of detection
      (LOD) (0.05-0.21MUg/mL), and limit of quantification (LOQ) (0.10-0.41MUg/mL). The
      on-line stop-flow heart-cutting 2D-LC system offers a potential approach to
      analyze compounds, which have similar structures but different polarities, in
      herbal medicines. 

PMID- 23870548
TI  - Avoid capture of interfering molecules in cardiac troponin immunoassays: working
      in shifts.

PMID- 23870549
TI  - Retraction: MyoD-dependent regulation of NF-kappaB activity couples cell-cycle
      withdrawal to myogenic differentiation.

PMID- 23870550
TI  - [False positive results: The imaginary invalid syndrome].

PMID- 23870551
TI  - [Effectiveness of the Mini-Mental State for detection of cognitive impairment in
      primary care].
AB  - OBJECTIVE: To evaluate the diagnostic accuracy (DA) of the Mini-Mental State
      (MMS) for the detection of cognitive impairment (CI) in Primary Care (PC) and to
      determine the best conditions of use for that purpose. DESIGN: Pooled analysis of
      two prospective, double blind, studies on the evaluation of diagnostic tools with
      complete verification that were conducted in Madrid and Granada (Spain). SETTING:
      The MMS was administered in PC and the final cognitive diagnosis (gold standard)
      was made in Specialized Care. PARTICIPANTS: Subjects with cognitive complaints or
      suspected of having CI were consecutively recruited in the PC clinic. PRINCIPAL
      MEASURES: The DA of the MMS was evaluated using the area under the receiver
      operating characteristic (ROC) curve (AUC). The best cut-off point was selected
      according to the ratio of cases correctly classified (RCC) and to the kappa
      index. Direct (MMSd) and age- and education-adjusted (MMSa) total scores were
      analyzed separately. RESULTS: In the total sample of 360 subjects (214 CI), the
      DA of the MMSd was significantly superior to that of the MMSa (0.84+/-0.02 vs
      0.82+/-0.02, p<=.001). The yield obtained by the best cut-off point of the MMSd
      (22/23) was modest (RCC 0.77, kappa 0.52+/-0.05) and was not improved by any MMSa
      cut-off point. CONCLUSION: The DA of the MMS for detection of CI in PC was modest
      and did not improve with adjustment of the score by age and education. The best
      cut-off point was 22/23, inferior to the usually recommended cut-off.

PMID- 23870552
TI  - Site-specific gene targeting using transcription activator-like effector (TALE)
      based nuclease in Brassica oleracea.
AB  - Site-specific recognition modules with DNA nuclease have tremendous potential as
      molecular tools for genome targeting. The type III transcription activator-like
      effectors (TALEs) contain a DNA binding domain consisting of tandem repeats that
      can be engineered to bind user-defined specific DNA sequences. We demonstrated
      that customized TALE-based nucleases (TALENs), constructed using a method called
      "unit assembly", specifically target the endogenous FRIGIDA gene in Brassica
      oleracea L. var. capitata L. The results indicate that the TALENs bound to the
      target site and cleaved double-strand DNA in vitro and in vivo, whereas the
      effector binding elements have a 23 bp spacer. The T7 endonuclease I assay and
      sequencing data show that TALENs made double-strand breaks, which were repaired
      by a non-homologous end-joining pathway within the target sequence. These data
      show the feasibility of applying customized TALENs to target and modify the
      genome with deletions in those organisms that are still in lacking gene target
      methods to provide germplasms in breeding improvement. 

PMID- 23870553
TI  - Metallothionein 2A inhibits NF-kappaB pathway activation and predicts clinical
      outcome segregated with TNM stage in gastric cancer patients following radical
      resection.
AB  - BACKGROUND: Metallothionein 2A (MT2A) as a stress protein, plays a protective
      role in gastric mucosal barrier. Its role in the development of gastric cancer
      (GC) is unclear. The mechanism of MT2A will be investigated in gastric
      tumorigenesis. METHODS: MT2A expression was detected in 973 gastric specimens.
      The biological function was determined through ectopic expressing MT2A in vitro
      and in vivo. The possible downstream effectors of MT2A were investigated in NF
      kappaB signaling. The protein levels of MT2A, IkappaB-alpha and p-IkappaB-alpha
      (ser32/36) expression were analyzed in a subset of 258 patients by IHC staining.
      The prognostic effects of MT2A, status of IkappaB-alpha and TNM stage were
      evaluated using the Kaplan-Meier method and compared using the log-rank test.
      RESULTS: Decreased MT2A expression was detected in cell lines and primary tumors
      of GC. In clinical data, loss of MT2A (MT2A + in Normal (n =171, 76.0%);
      Intestinal metaplasia (n = 118, 50.8%); GC (n = 684. 22.4%, P < 0.001)) was
      associated with poor prognosis (P < 0.001), advanced TNM stage (P = 0.05), and
      down-regulation of IkappaB-alpha expression (P < 0.001). Furthermore, MT2A was
      the independent prognostic signature segregated from the status of IkappaB-alpha
      and pathological features. In addition, MT2A inhibited cell growth through
      apoptosis and G2/M arrest, which negatively regulated NF-kappaB pathway through
      up-regulation of IkappaB-alpha and down-regulation of p-IkappaB-alpha and cyclin
      D1 expression. CONCLUSIONS: MT2A might play a tumor suppressive activity through
      inhibiting NF-kappaB signaling and may be a prognostic biomarker and potential
      target for individual therapy of GC patients.

PMID- 23870554
TI  - Sample size calculation for multicentre efficacy trials of blood-stage malaria
      antigens.
AB  - BACKGROUND: Sample size has increasingly become a prerequisite for grant
      approval. Study size calculations for multicentre trials are more complicated
      because these sites present different assumptions on incidence of disease
      expected in the control group; this then changes the mechanism of sample size
      determination. This paper suggested an alternative approach to estimating study
      size in multicentre vaccine efficacy trials. METHODS: The approach suggested in
      this paper was to determine the expected number of events for a given sample size
      under set of different assumptions. The power was then calculated given the
      expected number of events under the set of assumptions so as to assess the
      sensitivity of the sample size. The approach was then illustrated assuming a
      malaria vaccine efficacy trial planned in four centres. RESULTS: The approach
      showed that by assuming 30% cumulative incidence of malaria in three of the
      centres and 10% cumulative incidence in the other centre, a sample size of 460
      children in each centre (total 1,840) corresponding to a total of 339 events
      gives 90% power to detect vaccine efficacy of 30% at 5% level of significance,
      allowing for 15% loss to follow-up. However, if the incidence is lower than
      anticipated or a centre drops out altogether the power will be low. But this
      would not have much effect if it were a low incidence centre. Rather, it might
      have major effect if it were a high incidence centre. DISCUSSION: Decision on
      recruitment depends on whether separate estimates of efficacy in each
      transmission level are reasonable. If not, equal numbers can be recruited, which
      then gives safety data for each site and overall efficacy. Recruiting all or most
      subjects in the highest transmission site can minimize sample size but may be
      better to spread the risk due to uncertainty about incidence due to year to year
      variation and also the possibility of a site dropping due to political or other
      unforeseen problems. CONCLUSION: The approach demonstrated the potential of
      estimating the expected number of events required to give a specified power for
      multicentre efficacy trails of blood stage malaria antigens.

PMID- 23870603
TI  - Incidental perivascular epithelioid cell tumor in an inguinal hernia sac.
AB  - Perivascular epithelioid tumors (PEComa) are uncommon mesenchymal neoplasms
      demonstrating positivity for muscular and melanocytic immuno-markers. Included in
      this category are angiomyolipoma, lymphangioleiomyomatosis, and clear cell sugar
      tumors. Lesions which do not fit into these categories are classified as "not
      otherwise specified". We present a case of an incidentally discovered PEComa
      within inguinal hernia sac contents in a 70-year-old woman. It consisted of
      spindled and epithelioid cells with bland oval nuclei, small nucleoli and clear
      to light eosinophilic cytoplasm. There was no atypia or mitoses. The lesion was
      strongly positive for HMB45 and smooth muscle actin. Pelvic soft tissue and
      peritoneal PEComas are rarely reported in literature and very little is known
      about their prognosis. We discuss the immunohistochemistry, differential
      diagnosis, and pathogenesis of PEComas. 

PMID- 23870604
TI  - Factors influencing variability in clinical trials and in individuals' responses
      to treatment.

PMID- 23870605
TI  - Pharmacokinetic comparison of 2 fixed-dose combination tablets of amlodipine and
      valsartan in healthy male Korean volunteers: a randomized, open-label, 2-period,
      single-dose, crossover study.
AB  - BACKGROUND: Amlodipine and valsartan have different mechanisms of action, and it
      is known that the combination therapy with the 2 drugs increases treatment
      effects compared with the monotherapy with each drug. A fixed-dose combination
      (FDC) drug is a formulation including fixed amounts of active drug ingredients
      combined in a single dosage form that is expected to improve medication
      compliance. OBJECTIVE: The goal of this study was to compare the pharmacokinetic
      profiles of single administration of a newly developed FDC tablet containing
      amlodipine orotate 10 mg and valsartan 160 mg (test formulation) with the
      conventional FDC tablet of amlodipine besylate 10 mg and valsartan 160 mg
      (reference formulation) in healthy male Korean volunteers. METHODS: This was a
      randomized, open-label, single-dose, 2-way crossover study. Eligible subjects
      were between the ages of 20 and 50 years and within 20% of their ideal weight.
      Each subject received a single dose of the reference and the test formulations,
      with a 14-day washout period between formulations. Blood samples were collected
      up to 144 hours after the dose, and pharmacokinetic parameters were determined
      for amlodipine and valsartan. Adverse events were evaluated based on subject
      interviews and physical examinations. RESULTS: Forty-eight of the 50 enrolled
      subjects completed the study. For both amlodipine and valsartan, the primary
      pharmacokinetic parameters were included in the range for assumed bioequivalence,
      yielding 90% CI ratios of 0.9277 to 0.9903 for AUC(0-last) and 0.9357 to 1.0068
      for C(max) in amlodipine, and 0.9784 to 1.1817 for AUC(0-last) and 0.9738 to
      1.2145 for C(max) in valsartan. Dizziness was the most frequently noted adverse
      event, occurring in 4 subjects with the test formulation, followed by
      oropharyngeal pain occurring in 1 subject with the test formulation and 3
      subjects with the reference formulation. All other adverse events occurred in <3
      subjects. CONCLUSIONS: These findings suggest that the pharmacokinetics of the
      newly developed FDC tablet of amlodipine and valsartan did not differ
      significantly from the conventional FDC tablet in these healthy Korean male
      subjects. Both formulations were well tolerated, with no serious adverse events
      observed. ClinicalTrials.gov identifier: NCT01823913.

PMID- 23870606
TI  - Fluticasone/Formoterol combination therapy compared with monotherapy in
      adolescent and adult patients with mild to moderate asthma.
AB  - OBJECTIVES: This study investigated the efficacy and tolerability of a new asthma
      therapy combining fluticasone propionate and formoterol fumarate
      (fluticasone/formoterol)*, administered twice daily (BID) via a single aerosol
      inhaler, compared with fluticasone propionate (fluticasone) or formoterol
      fumarate (formoterol) administered alone, in patients with mild to moderate
      asthma. METHODS: Patients aged >=12 years were evenly randomized to 12 weeks of
      treatment with fluticasone/formoterol (100/10 ug BID), fluticasone (100 ug BID),
      or formoterol (10 ug BID), in this multicenter, double-blind, parallel-group,
      study. The 2 coprimary end points were: (1) change in forced expiratory volume in
      1 second (FEV(1)) from morning predose at baseline to predose at week 12 for the
      comparison of the combination product with formoterol alone; and (2) change in
      FEV(1) from morning predose at baseline to 2 hours postdose at week 12 for the
      comparison of the combination product with fluticasone alone. The secondary
      objective was to demonstrate the efficacy of fluticasone/formoterol using other
      pulmonary function tests and clinical end points. Tolerability was assessed based
      on adverse events, clinical laboratory tests and vital sign evaluations. RESULTS:
      Statistically significant differences were demonstrated for the 2 coprimary end
      points. Fluticasone/formoterol combination therapy showed significantly greater
      improvements from baseline to end of study in the change in predose FEV(1)
      compared with formoterol (least squares [LS] mean treatment difference, 0.118 L
      [95% CI, 0.034-0.201; P = 0.006]) and the change in predose compared with 2 hours
      postdose FEV(1) versus fluticasone (LS mean treatment difference, 0.122 L [95%
      CI, 0.040-0.204; P = 0.004]). Statistical analyses of the secondary efficacy
      endpoints revealed that evaluations of lung function, asthma exacerbations,
      asthma symptoms, rescue medication use and asthma control were supportive overall
      of the superior efficacy of fluticasone/formoterol combination therapy compared
      with its individual components; were supportive overall of the efficacy of
      fluticasone/formoterol combination therapy compared with its individual
      components. Since the secondary endpoints were analyzed using the sequential
      gatekeeper approach, only the mean change from baseline to final week in morning
      peak expiratory flow rate between the combination-therapy and formoterol groups
      returned statistically significant results (least squares mean difference, 20.05
      [95% CI, 7.631-32.472; P = 0.002]). The fluticasone/formoterol combination
      therapy had a good tolerability profile over the 12-week treatment period.
      CONCLUSIONS: Fluticasone/formoterol had a good tolerability profile and showed
      statistically superior efficacy for the two co-primary endpoints compared to
      fluticasone or formoterol, in adolescents and adults with mild to moderate
      asthma. ClinicalTrials.gov identifier: NCT00394199.

PMID- 23870607
TI  - Mixed treatment comparison meta-analysis of aspirin, warfarin, and new
      anticoagulants for stroke prevention in patients with nonvalvular atrial
      fibrillation.
AB  - BACKGROUND: Warfarin and aspirin are used to prevent stroke in patients with
      atrial fibrillation (AF). There are inherent challenges with both treatments,
      including variable and inconsistent benefit and increased bleeding risks. The
      availability of new anticoagulants offers some alternatives. OBJECTIVE: A mixed
      treatment comparison meta-analysis to evaluate direct and indirect treatment data
      including aspirin, warfarin apixaban, dabigatran, edoxaban, and rivaroxaban for
      the prevention of primary or secondary stroke in patients with AF. METHODS: A
      comprehensive, systematic literature search was conducted to identify randomized
      trials comparing aspirin, warfarin, apixaban, dabigatran, edoxaban, and
      rivaroxaban in patients with AF requiring treatment for stroke prevention. Open
      label and blinded designs were included if they evaluated any stroke or any
      bleeding event. Data on stroke and bleeding events were abstracted, verified,
      evaluated, scored, and entered into Aggregate Data Drug Information System
      version 1.16 to generate a mixed treatment comparison meta-analysis. Direct and
      indirect comparisons were evaluated, and we looked for inconsistency in closed
      loop structures. Data are reported as rate ratios with 95% credible intervals. In
      addition, we reviewed variance statistics and explored variance with node
      splitting models. RESULTS: Our literature search yielded 30 articles, 21 of which
      were included. All treatments except aspirin reduced the risk of any stroke
      compared with placebo. Warfarin (0.43 [0.33-0.57]), apixaban (0.37 [0.27-0.54]),
      dabigatran (0.34 [0.21-0.57]), rivaroxaban (0.36 [0.22-0.60]), and aspirin with
      clopidogrel (0.73 [0.53-0.99]) were more protective than aspirin alone. Warfarin
      and the new anticoagulants were similar in the reduction of stroke, vascular
      death, and mortality. There was no difference in major bleeding between any
      treatment group. There were more nonmajor bleeding events when comparing warfarin
      and apixaban (1.83 [1.05-4.03]); no other differences between warfarin and the
      other new anticoagulants were found. CONCLUSIONS: This mixed treatment comparison
      meta-analysis found similarity between warfarin and the new anticoagulants with
      the exception of one comparison, in which warfarin was associated with more non
      major bleeding than apixaban. Thus, the new anticoagulants are therapeutically
      comparable when warfarin is inappropriate.

PMID- 23870608
TI  - The pharmacokinetics and safety of a fixed-dose combination of acetylsalicylic
      acid and clopidogrel compared with the concurrent administration of
      acetylsalicylic acid and clopidogrel in healthy subjects: a randomized, open
      label, 2-sequence, 2-period, single-dose crossover study.
AB  - BACKGROUND: Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid
      (ASA) is used for the treatment of acute coronary syndrome. A combined
      formulation of ASA and clopidogrel has been developed to provide dosing
      convenience and improve adherence. OBJECTIVE: This study was designed to compare
      the pharmacokinetic properties and safety profile of a fixed-dose combination
      formulation of ASA and clopidogrel with concurrent administration of each agent
      in healthy male Korean volunteers. METHODS: This single-dose, randomized, open
      label, 2-period crossover study was conducted in 64 healthy Korean volunteers.
      Equal numbers of eligible participants were randomly assigned to receive either
      the fixed-dose combination of ASA 100 mg and clopidogrel 75 mg or the free
      combination of each agent followed by a 7-day washout period and then
      administration of the alternate formulation. Serial blood samples were collected
      immediately before and after dosing for 24 hours. The safety profile was
      evaluated by using adverse events (AEs), which were assessed by physical
      examination, vital signs, ECGs, clinical laboratory tests, and interviews. The 2
      formulations were considered to be bioequivalent if the 90% CIs for the log
      transformed C(max) and AUC(0-last) values were within the predetermined range of
      0.8 to 1.25. RESULTS: Sixty-four volunteers (mean [SD] age, 27.51 [8.15] years;
      weight, 68.55 [7.86] kg; height, 173.80 [5.94] cm) were enrolled, and 63
      completed the study. For ASA, the 90% CIs for the geometric mean ratios of C(max)
      and AUC(0-last) were 0.9483 to 1.1717 and 0.9946 to 1.1020, respectively. For
      salicylic acid, the 90% CIs were 0.9614 to 1.0396 for C(max) and 0.9778 to 1.0163
      for AUC(0-last). For clopidogrel, the 90% CIs were 0.9809 to 1.2562 for C(max)
      and 0.9674 to 1.2073 for AUC(0-last). Six of the 20 AEs reported were drug
      related: decreased hemoglobin levels (n = 2), fever (n = 1), and headache (n = 1)
      with the test formulation and increased alanine aminotransferase levels (n = 1)
      and dyspepsia (n = 1) with the reference formulation. All of the drug-related AEs
      were transient and mild in severity. CONCLUSIONS: The fixed-dose combination of
      ASA and clopidogrel 100 mg/75 mg did not meet the regulatory criteria for
      bioequivalence as defined by the Korea Food and Drug Administration. Both
      formulations were well tolerated in these healthy male Korean subjects.
      ClinicalTrials.gov Identifier: NCT01448330.

PMID- 23870609
TI  - The role of adiponectin as a compensatory mediator for the primary secretory
      defect in latent autoimmune diabetes in adults.
AB  - BACKGROUND: Increased adiposity in patients with newly diagnosed type 2 diabetes
      mellitus (DM), as well as in patients who do not have DM, affects the regulation
      of insulin sensitivity and the metabolic effects of adiponectin. OBJECTIVE: The
      goal of this study was to investigate the relationship between plasma adiponectin
      levels and obesity in patients developing DM mainly due to an early decline in
      beta-cell function. METHODS: We studied 29 patients with latent autoimmune
      diabetes in adults (LADA), 38 patients with type 1 DM, and 55 healthy volunteers.
      RESULTS: Plasma adiponectin levels, adjusted for body mass index (BMI), were
      higher in patients with type 1 DM than in controls (P < 0.001) and similar to
      those in patients with LADA (P = 0.464). Plasma adiponectin levels were higher in
      LADA patients compared with controls (P < 0.001). In LADA patients, plasma
      adiponectin levels, adjusted for BMI, correlated significantly with insulin
      resistance (beta coefficient, -6.453 [2.772]; P = 0.028). Interestingly, this
      relationship in LADA patients was significant in more overweight patients (beta
      coefficient, -7.142 [3.249]; P = 0.048) but not in leaner patients (P = 0.571), a
      finding that was not confirmed through the results in the controls (P = 0.520 and
      P = 0.992, respectively). CONCLUSIONS: In patients with LADA, increases in plasma
      adiponectin levels, after adjustment for BMI, could act as a mediator for
      improvement in insulin sensitivity and thus compensate for the primary secretory
      defect. This effect seems more profound in more overweight subjects than in
      leaner subjects.

PMID- 23870610
TI  - The effect of ticagrelor on the metabolism of midazolam in healthy volunteers.
AB  - BACKGROUND: In vitro studies have demonstrated that ticagrelor, an oral
      antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450
      (CYP) 3A. Thus, potential CYP3A-mediated drug-drug interactions may occur.
      OBJECTIVES: The goal of this article was to report study results on the effect of
      ticagrelor on the pharmacokinetics of oral midazolam (oral midazolam study) and
      oral versus intravenous (IV) midazolam (oral/IV midazolam study). Secondary
      objectives included assessing the effect of midazolam on ticagrelor
      pharmacokinetic parameters, and the safety and tolerability of
      ticagrelor/midazolam coadministration. METHODS: Two randomized crossover studies
      were conducted in healthy volunteers (n = 28 in each) with ticagrelor and
      midazolam. In the first study, volunteers received oral ticagrelor (400 mg daily)
      or placebo for 6 days, then oral midazolam (7.5 mg). The second study regimen was
      a single dose of ticagrelor 270 mg, then ticagrelor 180 mg BID for 6 days with a
      single oral (7.5 mg) or IV (2.5 mg) dose of midazolam. RESULTS: After oral
      midazolam administration, ticagrelor significantly reduced the AUC(0-infinity) of
      midazolam (30%-32%) and 4-hydroxymidazolam (42%-47%) but not 1-hydroxymidazolam.
      After administration of IV midazolam, ticagrelor reduced the AUC(0-infinity) of
      midazolam (12%) and 4-hydroxymidazolam (23%) but not 1-hydroxymidazolam.
      CONCLUSIONS: These results indicate that ticagrelor can weakly activate the
      metabolism of midazolam to its major 1'-hydroxy metabolite, and at the same time,
      seems to weakly inhibit midazolam 4'-hydroxylation. Furthermore, ticagrelor
      affects both hepatic and intestinal CYP3A activity.

PMID- 23870611
TI  - Effect of food on the pharmacokinetic properties of the oral sarpogrelate
      hydrochloride controlled-release tablet in healthy male Korean subjects.
AB  - BACKGROUND: A new controlled-release formulation of sarpogrelate, a 5
      hydroxytryptamine receptor subtype 2 antagonist that blocks serotonin-induced
      platelet aggregation, has been developed for once-daily administration.
      OBJECTIVE: This study evaluated the effect of food on the pharmacokinetic
      properties of controlled-release sarpogrelate (sarpogrelate CR) in healthy
      volunteers. METHODS: A randomized, open-label, two-period, two-treatment
      crossover study was performed in healthy male Korean subjects. Following an
      overnight fast, a single dose of sarpogrelate CR 300 mg was administered either
      in the fasted condition or immediately after a high-fat breakfast.
      Pharmacokinetic parameters were calculated using a noncompartmental analysis.
      Tolerability was determined using clinical laboratory testing and physical
      examination, including vital sign measurements, electrocardiography, and
      interviews with the volunteers regarding adverse events (AEs). RESULTS: A total
      of 24 healthy subjects were enrolled, 23 of whom completed the study (mean
      [range] age, 26 years [21-45]; weight, 68.1 kg [56.0-79.9]; body mass index, 22.1
      kg/m(2) [18.8-25.0]). Sarpogrelate C(max) and AUC(last) were decreased In the fed
      condition compared with those in the fasted condition, with geometric mean ratios
      (90% CI) of 0.4868 (0.4041-0.5864) and 0.7394 (0.6809-0.8028), respectively.
      T(max) was delayed from 0.75 to 4.0 hours after a high-fat meal, but the fed
      condition exhibited a similar elimination profile to that of the fasted
      condition. The most commonly reported AE was headache (n = 2), and other AEs were
      reported in 1 subject each. All of the AEs were considered mild in intensity, and
      the participants recovered without treatment. CONCLUSIONS: Compared with the
      administration of sarpogrelate CR 300 mg in the fasted condition, administration
      with food was associated with a decreased rate and extent of absorption, as
      assessed by C(max) and AUC(last), respectively. The drug was well-tolerated by
      the healthy subjects in this study.

PMID- 23870612
TI  - Quetiapine fumarate for the treatment of multiple sclerosis: focus on myelin
      repair.
AB  - Multiple sclerosis (MS) is a central nervous system disorder that is associated
      with progressive oligodendrocyte and neuronal loss, axonal degeneration, and
      demyelination. Several medications that mitigate immune abnormalities reduce both
      the frequency of relapses and inflammation on magnetic resonance imaging, leading
      to improved outcomes for people with the relapsing-remitting form of MS. However,
      there are no treatments for the progressive forms of MS where neurons and axons
      continue to degenerate; here, neuroprotective therapies, or medications that
      rebuild myelin to confer axonal well-being, may be useful. Quetiapine fumarate is
      an atypical antipsychotic with reported remyelinating and neuroprotective
      properties in inflammatory and noninflammatory models of demyelination, including
      experimental autoimmune encephalomyelitis, and both cuprizone- and global
      cerebral ischemia-induced demyelination. Preclinical studies suggest that
      quetiapine may exert these effects by stimulating proliferation and maturation of
      oligodendrocytes, releasing neurotrophic factors, increasing antioxidant
      defences, scavenging for free radicals, and inhibiting activated microglia,
      astrocytes, and T lymphocytes. Additionally, quetiapine may be beneficial for
      psychiatric and nonpsychiatric symptoms of MS including depression, anxiety,
      insomnia, and possibly even pain. These data indicate that clinical trials are
      justified to determine the safety, tolerability, and efficacy of quetiapine
      fumarate in MS. 

PMID- 23870614
TI  - Simvastatin decreases the level of heparin-binding protein in patients with acute
      lung injury.
AB  - BACKGROUND: Heparin-binding protein is released by neutrophils during
      inflammation and disrupts the integrity of the alveolar and capillary endothelial
      barrier implicated in the development of acute lung injury and systemic organ
      failure. We sought to investigate whether oral administration of simvastatin to
      patients with acute lung injury reduces plasma heparin-binding protein levels and
      improves intensive care unit outcome. METHODS: Blood samples were collected from
      patients with acute lung injury with 48 h of onset of acute lung injury (day 0),
      day 3, and day 7. Patients were given placebo or 80 mg simvastatin for up to 14
      days. Plasma heparin-binding protein levels from patients with acute lung injury
      and healthy volunteers were measured by ELISA. RESULTS: Levels of plasma heparin
      binding protein were significantly higher in patients with acute lung injury than
      healthy volunteers on day 0 (p = 0.011). Simvastatin 80 mg administered enterally
      for 14 days reduced plasma level of heparin-binding protein in patients. Reduced
      heparin-binding protein was associated with improved intensive care unit
      survival. CONCLUSIONS: A reduction in heparin-binding protein with simvastatin is
      a potential mechanism by which the statin may modify outcome from acute lung
      injury. TRIAL REGISTRATION: Current controlled trials: ISRCTN70127774.

PMID- 23870615
TI  - GPs' recognition of death in the foreseeable future and diagnosis of a fatal
      condition: a national survey.
AB  - BACKGROUND: Nowadays, palliative care is considered as a care continuum that may
      start early in the course of the disease. In order to address the evolving needs
      of patients for palliative care in time, GPs should be aware in good time of the
      diagnosis and of the imminence of death. The aim of the study was to gain insight
      into how long before a non-sudden death the diagnosis of the disease ultimately
      leading to death is made and on what kind of information the diagnosis is based.
      In addition, we aimed to explore when, and based on what kind of information, GPs
      become aware that death of a patient will be in the foreseeable future. METHODS:
      A written questionnaire focusing on the GPs' experiences with their last patient
      who died non-suddenly was sent to a random representative sample of 850 GPs in
      the Netherlands. RESULTS: The data were analysed of the 297 GPs who responded.
      76% of the reported cases were cancer patients and 24% were patients with another
      non-sudden cause of death. The diagnosis was made only in the last week of life
      for 15% of the non-cancer patients and 1% of the patients with cancer. GPs were
      most likely to have been informed of the diagnosis by the medical specialist,
      although particularly in the case of non-cancer patients GPs also relied on their
      own assessment of the diagnosis or on other information sources.The GP remained
      unaware that the patient would die in the foreseeable future until the last week
      of life in 26% of the non-cancer group, while this was the case for only 6% of
      the cancer patients. GP's awareness was most likely to be based on the GP's own
      observations of problems and/or symptoms. CONCLUSIONS: The GP often only becomes
      aware of a fatal diagnosis and of death in the foreseeable future at a late stage
      in the disease trajectory, particularly in the case of non-cancer patients. It
      can be assumed that if the diagnosis and the nearing death are only recognised at
      a late stage, palliative care is either started at a very late stage or not at
      all.

PMID- 23870616
TI  - Medicinal plants used for the treatment of various skin disorders by a rural
      community in northern Maputaland, South Africa.
AB  - BACKGROUND: Skin diseases have been of major concern recently due to their
      association with the Human Immunodeficiency Virus and Acquired Immunity
      Deficiency Syndrome (HIV/AIDS). The study area (northern Maputaland) has the
      highest HIV infection rate in South Africa, which made them more prone to a wide
      range of skin conditions. Fungal infections due to the hot climate and
      overcrowding households are common in this area, as well as burn accidents due to
      the use of wood as the major fuel for cooking. It is known that the lay people in
      this area depend on medicinal plants for their primary health care. However no
      survey has been done in northern Maputaland to document the medicinal plants used
      to treat various skin disorder. METHODS: Interviews were undertaken at 80
      homesteads, using structured questionnaires. The focus was on plants used for
      dermatological conditions and information regarding vernacular plant names, plant
      parts used, preparation (independently and in various combinations) and
      application was collected. RESULTS: A total of 87 lay people, both male (22%) and
      female (78%) were interviewed on their knowledge of medicinal plants used to
      treat disorders of the skin. Forty-seven plant species from 35 families were
      recorded in the present survey for the treatment of 11 different skin disorders
      including abscesses, acne, burns, boils, incisions, ringworm, rashes, shingles,
      sores, wounds and warts. When searching the most frequently used scientific
      databases (ScienceDirect, Scopus and Pubmed), nine plant species (Acacia burkei,
      Brachylaena discolor, Ozoroa engleri, Parinari capensis, subsp. capensis,
      Portulacaria afra, Sida pseudocordifolia, Solanum rigescens, Strychnos
      madagascariensis and Drimia delagoensis) were found to be recorded for the first
      time globally as a treatment for skin disorders. Fourteen plant combinations were
      used. Surprisingly, the application of enema's was frequently mentioned.
      CONCLUSIONS: The preference of traditional medicine over allopathic medicine by
      most of the interviewees strengthens previous studies on the importance that
      traditional medicine can have in the primary health care system in this rural
      community. Studies to validate the potential of these plants independently and in
      their various combinations is underway to provide insight into the anti-infective
      role of each plant.

PMID- 23870618
TI  - Variable phenotype and severity of sialidosis expressed in two siblings
      presenting with ataxia and macular cherry-red spots.
AB  - Sialidosis is a rare lysosomal storage disease with a wide clinical spectrum
      ranging from nearly asymptomatic to severe presentations. We present two
      Brazilian siblings with sialidosis, the first patient with sialidosis type I, and
      the second with sialidosis type II. Our report reinforces the relevance of
      ophthalmologic evaluation in patients with early and late-onset ataxias, if an
      association with myoclonus or dysmorphic features is present or not. Also, we
      demonstrate that sialidosis might represent a single genetic entity with variable
      clinical expression through these two siblings. 

PMID- 23870619
TI  - Relationship of olfactory function with olfactory bulbus volume, disease duration
      and Unified Parkinson's disease rating scale scores in patients with early stage
      of idiopathic Parkinson's disease.
AB  - We aimed to investigate the relationship between olfactory function and olfactory
      bulbus (OB) volume, disease duration and Unified Parkinson's disease rating scale
      (UPDRS) scores in early stage idiopathic Parkinson's disease patients. The
      University of Pennsylvania Smell Identification Test (UPSIT) was used for the
      evaluation of olfactory function. UPSIT scores for patients with Parkinson's
      disease were significantly lower than controls. There was no significant
      difference between stage 1 and stage 2 patients. OB volumes were higher in stage
      1 and 2 patients than controls, but there was no statistical difference between
      the three groups. No significant correlation was found between UPSIT and UPDRS
      total scores, nor between UPSIT scores and disease duration in stage 1 and 2
      patients. According to our results, we propose UPSIT be used as a screening test
      to diagnose presymptomatic patients, but not OB volumes.

PMID- 23870620
TI  - Surgical treatment of high grade dural arteriovenous fistulae.
AB  - Dural arteriovenous fistulae (dAVF) with direct cortical venous drainage (CVD,
      Borden Type III) have a high risk of hemorrhage, particularly when symptomatic.
      Stereotactic radiosurgery is therefore not recommended, and endovascular
      treatment can be limited by access, incomplete obliteration, and recanalization.
      Of 70 cerebral dAVF seen at our institution over the past 8 years, 35 were Borden
      Type III (50%). Twenty-four were treated via microsurgery (69%). Presentation
      included hemorrhage in nine patients (38%), nonhemorrhagic neurologic deficits in
      five (21%), asymptomatic in five (21%), headache in three (13%), and seizure in
      two patients (8%). Only eight of 19 patients with symptomatic dAVF were
      independent (modified Rankin Scale [mRS] 0-2) preoperatively (42%). The dAVF
      location was tentorial in six patients (25%), petrosal in six (25%), superior
      sagittal sinus in four (17%), torcular in two (7%), floor of the anterior fossa
      in two (7%), and sphenoid ridge, transverse-sigmoid, inferior sagittal sinus and
      jugular in one patient each (4%). Four patients had failed endovascular therapy
      (17%). The angiographic obliteration rate was 96%. The combined permanent
      morbidity and mortality rate was 17%. After a mean follow-up of 2.1 years, 13
      patients improved (54%), seven were the same, (29%) and four were worse (17%).
      Thirteen patients were asymptomatic (mRS 0, 54%), and 18 were independent (mRS 0
      2, 75%). Our results reinforce that surgical treatment of dAVF with direct CVD is
      associated with a high angiographic cure rate with acceptable morbidity and
      mortality, particularly in light of the lesions' natural history.

PMID- 23870621
TI  - Longer telomere length in patients with schizophrenia.
AB  - Previous studies have reported an association between shorter leukocyte telomere
      length and schizophrenia (SCZ). The aim of the present study was to replicate
      this finding in a large sample of SCZ patients (n=539) and population-based
      controls (n=519). In addition, the possible influence of SCZ severity on telomere
      length - as measured by age of onset, mode of onset, and course of the disorder -
      was investigated. Telomere length was negatively associated with age in both
      patients and controls. This is a consistently reported phenomenon, related to the
      problem of DNA end-replication. However, in contrast to previous findings, SCZ
      patients displayed longer telomeres compared to controls (p=0.015). No
      association was found with any SCZ-severity subphenotype. Interestingly, recent
      studies have reported associations between longer leukocyte telomere length and
      both smaller hippocampal volume, and poorer episodic memory performance. Both
      phenotypes are common in patients with SCZ. Further studies are warranted to
      investigate whether the present association between SCZ and increased telomere
      length was driven by such associations, or rather by association with the
      clinical disease per se or other associated phenotypes, endophenotypes or
      lifestyle factors. 

PMID- 23870622
TI  - Experimental measurement of forces and energies associated with capillary rise in
      a vertical tube.
AB  - We examined the forces and energies associated with liquid rising in a capillary
      tube. Glass and polytetrafluorethylene (PTFE) tubes with diameter ranging from
      0.5 to 1.4mm were brought into contact with ethylene glycol, glycerol or silicone
      oil to initiate rise. We measured the force generated by the rising liquids with
      a tensiometer and plotted them against rise height. From these plots, we
      estimated the change in potential energy. For a given liquid-solid combination,
      the change in potential energy was equal to the difference between the work of
      wetting and viscous dissipation in the bulk of the liquid; potential energy
      values were independent of tube diameter and ranged from 7 mJ/m(2) for silicone
      oil rising through PTFE to 33 mJ/m(2) for glycerol and glass.

PMID- 23870623
TI  - Effect of rehabilitation length of stay on outcomes in individuals with traumatic
      brain injury or spinal cord injury: a systematic review protocol.
AB  - BACKGROUND: Rehabilitation interventions are a key component of the services
      required by individuals with neurotrauma to recover or compensate for altered
      abilities and achieve optimal social participation. Primary studies have produced
      evidence of the effect of rehabilitation length of stay on individuals with
      neurotrauma. However, to date no systematic review of this evidence has been
      performed. This makes it difficult for managers and clinicians to base their
      rehabilitation practices upon evidence. METHOD: Supported by a committee of
      stakeholders, we will search electronic databases for research articles examining
      the association between length of stay or intensity of inpatient rehabilitation
      services and outcomes or the determinants of inpatient rehabilitation length of
      stay in adults with neurotrauma published after January 1990. Two researchers
      will independently screen the article titles and abstracts for inclusion. Two
      reviewers will independently extract the data. Primary outcomes of interest will
      be level of function, participation and return to work. If the data allow it, a
      meta-analysis of the studies will be performed. DISCUSSION: The results of this
      systematic review will clarify the factors that influence length of stay and
      intensity of rehabilitation services for individuals with TBI and SCI. They will
      give clinicians indications for optimal length of stay in these patient
      populations, contributing to better quality of care and better functional
      results. TRIAL REGISTRATION: This review protocol has been registered on the
      PROSPERO database (CRD42012003120) and is available at
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42012003120.

PMID- 23870624
TI  - [Characteristics of acute human immunodeficiency virus infection in three areas
      of Castilla-La Mancha, Spain].

PMID- 23870625
TI  - Preoperative estimation of seizure control after resective surgery for the
      treatment of epilepsy.
AB  - PURPOSE: Predicting seizure control after epilepsy surgery is difficult. The
      objectives of this work are: (a) to estimate the value of surgical procedure,
      presence of neuroimaging abnormalities, need for intracranial recordings,
      resection lobe, pathology, durations of epilepsy and follow-up period to predict
      postsurgical seizure control after epilepsy surgery and (b) to provide empirical
      estimates of successful outcome after different combinations of the above factors
      in order to aid clinicians in advising patients presurgically about the
      likelihood of success under their patients' individual circumstances. METHODS: We
      report postsurgical seizure control from all 243 patients who underwent resective
      surgery for epilepsy at King's College Hospital between 1999 and 2011. Among the
      243 patients, 233 had lobar or sub-lobar resections, 8 had multilobar resections
      and 2 had excision of a hypothalamic hamartoma. We examined the relation between
      postsurgical seizure control and type of surgical procedure, presence of
      neuroimaging abnormalities, pathology, resection lobe and the need of intra
      cranial electrodes to identify seizure onset. RESULTS: Among the 243 patients,
      126 (52%) enjoyed outcome grade I, 40 (16%) had grade II, 51 (21%) had grade III
      and 26 (11%) had grade IV (mean follow-up 41.1 months). Normal neuroimaging or
      need for intracranial recordings was not associated with poorer outcome. Patients
      undergoing temporal resections showed better outcome than those with frontal
      resections, due to the poor outcome seen in frontal patients with normal
      neuroimaging. Among temporal resections, there was no difference in outcome
      between patients with and without neuroimaging abnormalities. Among patients with
      lesions on imaging, temporal and frontal resections showed similar outcomes.
      Likelihood of favourable outcome under the patient's individual circumstances was
      estimated by the tables provided. There was an 8-9% decrease in the percentage of
      grade I between follow-up at 12 and >36 months. CONCLUSION: Overall, nearly 70%
      of patients undergoing resective surgery enjoy favourable post-surgical seizure
      control. Normal neuroimaging should not discourage surgery in temporal patients
      but is a negative prognostic sign in normal MRI frontal patients. There were no
      statistical differences in outcome between patients with neuroimaging lesions in
      frontal or temporal lobes.

PMID- 23870627
TI  - A randomized trial of artemether-lumefantrine and dihydroartemisinin-piperaquine
      in the treatment of uncomplicated malaria among children in western Kenya.
AB  - BACKGROUND: Artemether-lumefantrine (AL) was adopted as first-line treatment for
      uncomplicated malaria in Kenya in 2006. Monitoring drug efficacy at regular
      intervals is essential to prevent unnecessary morbidity and mortality. The
      efficacy of AL and dihydroartemisinin-piperaquine (DP) were evaluated for the
      treatment of uncomplicated malaria in children aged six to 59 months in western
      Kenya. METHODS: From October 2010 to August 2011, children with fever or history
      of fever with uncomplicated Plasmodium falciparum mono-infection were enrolled in
      an in vivo efficacy trial in accordance with World Health Organization (WHO)
      guidelines. The children were randomized to treatment with a three-day course of
      AL or DP and efficacy outcomes were measured at 28 and 42 days after treatment
      initiation. RESULTS: A total of 137 children were enrolled in each treatment arm.
      There were no early treatment failures and all children except one had cleared
      parasites by day 3. Polymerase chain reaction (PCR)-uncorrected adequate clinical
      and parasitological response rate (ACPR) was 61% in the AL arm and 83% in the DP
      arm at day 28 (p = 0.001). PCR-corrected ACPR at day 28 was 97% in the AL group
      and 99% in the DP group, and it was 96% in both arms at day 42. CONCLUSIONS: AL
      and DP remain efficacious for the treatment of uncomplicated malaria among
      children in western Kenya. The longer half-life of piperaquine relative to
      lumefantrine may provide a prophylactic effect, accounting for the lower rate of
      re-infection in the first 28 days after treatment in the DP arm.

PMID- 23870626
TI  - Betaine supplement enhances skeletal muscle differentiation in murine myoblasts
      via IGF-1 signaling activation.
AB  - BACKGROUND: Betaine (BET) is a component of many foods, including spinach and
      wheat. It is an essential osmolyte and a source of methyl groups. Recent studies
      have hypothesized that BET might play a role in athletic performance. However,
      BET effects on skeletal muscle differentiation and hypertrophy are still poorly
      understood. METHODS: We examined BET action on neo myotubes maturation and on
      differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR
      array, Western blot and immunofluorescence analysis to study the BET effects on
      morphological features of C2C12 and on signaling pathways involved in muscle
      differentiation and hypertrophy. RESULTS: We performed a dose-response study,
      establishing that 10 mM BET was the dose able to stimulate morphological changes
      and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to
      identify the expression profile of genes encoding proteins involved in IGF-1
      pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R)
      expression. Western blot and immunofluorescence analysis, performed in neo
      myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of
      Myosin Heavy Chain (MyHC) and neo myotubes length. CONCLUSIONS: Our findings
      provide the first evidence that BET could promote muscle fibers differentiation
      and increase myotubes size by IGF-1 pathway activation, suggesting that BET might
      represent a possible new drug/integrator strategy, not only in sport performance
      but also in clinical conditions characterized by muscle function impairment.

PMID- 23870628
TI  - [Midgut bleeding due to uncinariasis and diagnosed by capsule endoscopy: a
      clinical case].

PMID- 23870629
TI  - Survey of systems for comparative ranking of agents that pose a bioterroristic
      threat.
AB  - Strong efforts are made to improve preparedness for the prevention and
      counteraction of possible deliberate release of highly pathogenic biological
      agents at national and international level. An objective risk assessment for
      highly pathogenic biological agents is urgently needed for the purpose of
      prioritizing measures, evaluating the vulnerabilities and supporting rapid
      decisions on a scientific base in case of an emergency. Hitherto, several
      differing ranking schemes were developed. In general, the purpose of such ranking
      schemes is a comparative classification of agents under consideration of
      different transmission paths as well as agents threatening human and/or animal
      health. The analysed prioritization methods differ from qualitative to (semi
      )quantitative with each its benefits and disadvantages in preciseness of the
      result, complexity and duration of the assessment but also in comprehensibility.
      Mainly, risk was defined as the product of probability and impact. In this
      survey, factors frequently used for the assessment of the probability and impact
      of a deliberate agent release were identified. Main criteria for the probability
      of an application were the history of use, the accessibility of the agent and
      possible paths of introduction and contamination as well as the feasibility of
      agent production. For the estimation of the impact, mainly the agent's effects on
      human and/or veterinary public health, depending on the target population, were
      examined. This includes the morbidity and mortality rates as well as the severity
      of induced illness, possible measures for diagnosis, and treatment and
      prevention. Furthermore, the economic and socioeconomic consequences were
      considered. In this review, the authors give an overview on open-source
      publications dealing with risk ranking of biological agents by outlining the
      criteria that were applied for risk ranking. 

PMID- 23870630
TI  - The gait pattern is not impaired in subjects with external snapping hip: a
      comparative cross-sectional study.
AB  - BACKGROUND: Symptomatic external snapping hip is a painful condition, where pain
      in the trochantor region and limitations of daily activity dominate clinical
      findings. The aetiology of symptomatic external snapping hip is elusive, but
      previous studies have suggested that weakness of the hip abductors and an altered
      walking pattern may play a role in the development of symptomatic external
      snapping hip. The aim of this study was to compare the walking pattern and
      muscular activity of the hip muscles between subjects with symptomatic external
      snapping hip and healthy subjects. METHODS: Thirteen subjects with diagnosed
      symptomatic external snapping hip (age: 25.5 years) were matched with 13 healthy
      subjects (age: 25.6 years). Joint kinematics and kinetics of the lower extremity
      were quantified by the peak hip adduction angle; the average knee rotation range
      of motion (ROM) and the peak valgus knee angle after data recording using a Vicon
      612 motion capture system. Muscle activity was recorded bilaterally using surface
      electromyography (sEMG) on five muscles: gluteus maximus, gluteus medius, tensor
      fascia latae, rectus femoris and biceps femoris. A paired t-test was used to
      evaluate differences between the two groups. RESULTS: No significant differences
      were found between the groups concerning the peak hip adduction angle, the
      average knee rotation ROM, and the static valgus knee angle. No significant
      between-group differences were found concerning all other kinematics, kinetics or
      muscle activity. In subjects with symptomatic external snapping hip activity of
      the gluteus medius muscle during the acceptance phase of walking was 0.58 +/-
      0.19 whereas the activity was 0.68+/-0.07 in the asymptomatic group (p=0.115).
      CONCLUSIONS: No significant differences in the walking pattern were found between
      subjects with symptomatic external snapping hip and healthy subjects. This
      suggest that subjects with symptomatic external snapping hip does not have an
      impaired gait pattern.

PMID- 23870631
TI  - Relation between preoperative renal dysfunction and cardiovascular events
      (stroke, myocardial infarction, or heart failure or death) within three months of
      isolated coronary artery bypass grafting.
AB  - Renal dysfunction is related to long-term mortality and myocardial infarction
      after coronary artery bypass grafting (CABG). We aimed to investigate the
      association between preoperative renal dysfunction and early risk of stroke,
      myocardial infarction, or heart failure after CABG. From the Swedish Web-system
      for Enhancement and Development of Evidence-based care in Heart disease Evaluated
      According to Recommended Therapies registry, we included all 36,284 patients who
      underwent primary isolated CABG from 2000 to 2008 in Sweden. The Swedish National
      Inpatient Registry was used to obtain the primary end point, which was
      rehospitalization for stroke, myocardial infarction, or heart failure <=90 days
      after CABG. Logistic regression models were used to estimate the risk for the
      primary outcome and the secondary outcome of death from any cause, while
      adjusting for confounders. During 90 days of follow-up, there were 2,462
      cardiovascular events and 617 deaths. In total, 17% of patients developed acute
      kidney injury postoperatively. Odds ratios with 95% confidence intervals for
      cardiovascular events after adjustment for age, gender, atrial fibrillation, left
      ventricular ejection fraction, diabetes mellitus, peripheral vascular disease,
      and history of myocardial infarction, heart failure, or stroke was 1.24 (1.06 to
      1.45) in patients with an estimated glomerular filtration rate of 15 to 45
      ml/min/1.73 m(2) but became nonsignificant after acute kidney injury was
      introduced into the statistical model. The risk of death was significantly
      increased in patients with estimated glomerular filtration rate of 15 to 45
      ml/min/1.73 m(2) (odds ratio 1.76, 95% confidence interval 1.38 to 2.25) even
      after adjustment for all confounders. Renal dysfunction was associated with all
      cause mortality but not with cardiovascular events during the first 3
      postoperative months after primary isolated CABG.

PMID- 23870636
TI  - Combined circular multielectrode catheter and point-by-point ablation is superior
      to point-by-point ablation alone in eliminating atrial fibrillation.
AB  - BACKGROUND: Besides conventional point-by-point ablation, novel multielectrode
      catheters emerge for ablation of atrial fibrillation (AF). We sought to evaluate
      the clinical utility of a pulmonary vein (PV) isolation approach combining the
      advantages of both technologies. METHODS: The study included 240 consecutive AF
      patients (60+/-11 years, 68% males, 62% paroxysmal). In the combined ablation
      group (n=120), PV isolation was performed with a circular multielectrode catheter
      (PVAC, Medtronic Ablation Frontiers) and completed by conventional point-by-point
      ablation (NaviStar ThermoCool Catheter, Lasso/CARTO technology, Biosense
      Webster). In the point-by-point ablation group (n=120), PV isolation was
      performed with point-by-point ablation alone. RESULTS: Complete 1-year ablation
      success (freedom from any atrial arrhythmia off antiarrhythmic drugs) was more
      frequently observed in the combined ablation group (58.0% versus 43.3%, hazard
      ratio 1.72, 95% confidence interval 1.19-2.48, p=0.004). Also clinical success
      (>=90% reduction of arrhythmia burden on/off antiarrhythmic drugs) was
      significantly associated with the combined ablation approach (p=0.001). These
      associations remained significant after multivariable adjustment (both p<=0.005)
      and were not dependent on the type of AF. The rate of major adverse events (3.3%
      versus 2.5%) and the procedure time did not differ between groups. The
      fluoroscopy time, however, was significantly shorter in the combined ablation
      group (p<0.001) reflecting the reduced need for radiation during multielectrode
      catheter ablation. CONCLUSIONS: A combined PV isolation approach based on
      multielectrode catheter ablation and complementary point-by-point ablation is
      superior to point-by-point ablation alone and reveals to be safe. A potential
      explanation for these findings is the improved durability of ablation lesion
      after the combined ablation approach.

PMID- 23870637
TI  - The impact of vagotonic, adrenergic, and random type of paroxysmal atrial
      fibrillation on left atrial ablation outcomes.
AB  - BACKGROUND: Accumulating data have shown that the autonomic nervous system is
      strongly implicated in the genesis of atrial fibrillation (AF). The aim of this
      study was to assess the efficacy of a single ablation procedure in patients with
      vagotonic, adrenergic and random type of paroxysmal AF. METHODS AND RESULTS: The
      clinical records of consecutive patients with symptomatic, drug-refractory
      paroxysmal AF who underwent pulmonary vein antral isolation were analysed. The
      study population consisted of 104 patients (64 males, mean age 57.9 +/- 10.9
      years) with paroxysmal AF. Based on AF triggers, patients were classified in
      those with vagotonic (31.7%), adrenergic (17.3%) and random AF (51%). Subjects
      with adrenergic and random AF tended to be older (p: 0.104) and displayed a
      higher incidence of hypertension (p: 0.088) compared with those with vagotonic
      AF. Following a mean follow-up period of 14.7 +/- 7.4 months, 74 patients were
      free from arrhythmia recurrence (71.2%). Late arrhythmia recurrence (>3 months
      from the index procedure) occurred in 33.3%, 16.7% and 30.2% of patients with
      vagotonic, adrenergic and random AF, respectively (p: 0.434). Cox regression
      analysis showed that early AF recurrence [hazard ratio (HR) 15.76; 95% confidence
      interval (CI) 5.456-45.566, p: <0.001], left atrial volume (HR 0.969; 95% CI
      0.942-0.996, p: 0.025) and statin use (HR 6.828; 95% CI 2.078-22.437 p: 0.002)
      were independent predictors of late arrhythmia recurrence. CONCLUSIONS: In this
      study cohort, the type of paroxysmal AF was not associated with arrhythmia
      recurrence following left atrial ablation.

PMID- 23870638
TI  - Transplantation of preconditioned bone marrow mononuclear cells by AT2R
      stimulation improves infarcted heart function via enhanced cardiac mobilization
      of implanted cells.

PMID- 23870639
TI  - The natural history of coronary calcification: a meta-analysis from St Francis
      and EBEAT trials.
AB  - BACKGROUND AND AIM: Coronary artery calcium score (CACs) is an established
      quantitative tool for assessing subclinical atherosclerosis. The aim of this
      study was to assess in a meta-analysis model the natural history and
      reproducibility of CACs measurements obtained from St Francis and EBEAT trials.
      METHODS: We analysed data from 649 individuals: 443 on placebo with 2 year follow
      up from St Francis trial (Study A) and 209 on 10 mg atorvastatin with 1 year
      follow-up of EBEAT trial (Study B). Total CACs and that in the left coronary
      artery (LCA) branches, left main stem (LMS), left anterior descending (LAD), left
      circumflex (Cx) and right coronary artery (RCA) were analysed. In view of the
      wide CACs spectrum, data were logarithmically transformed before the analyses and
      mixed model analysis was used to evaluate the change of CACs over time. RESULTS:
      The overall agreement between the two measurements was fairly good, showing a
      small but significant increase in CAC: 68% of the group as a whole presented an
      increase in CACs, 23% of the cohort had negligible change in CACs of <10%
      irrespective of the baseline CACs; and the remaining 10% showed a fall in CACs.
      Both studies showed similar patterns. The analysis of individual coronary
      arteries showed significantly higher variability of measurements in the RCA than
      in the LCA. Males had higher baseline CACs than females, but the rate of
      progression was not different between genders, irrespectively of age and baseline
      score. CONCLUSION: The natural history of CACs was overtime progression in the
      majority of subjects, irrespective of gender. The higher variability in RCA
      measurements could be related to the low baseline CACs or exaggerated movement of
      the right side atrioventricular ring, whereas those for LCA branches are
      influenced by the branch allocation of the CACs. Large changes to and from zero,
      might be related to technical limitations.

PMID- 23870640
TI  - Rethinking cardiac resynchronization therapy: the impact of ventricular
      dyssynchrony on outcome.
AB  - OBJECTIVE: To analyze whether left ventricular dyssynchrony (LVD) at baseline is
      predictive for long-term outcome in heart failure (CHF) patients with left
      ventricular (LV) dysfunction and conduction disturbances treated with cardiac
      resynchronization therapy (CRT). METHODS: In 535 consecutive individuals with CHF
      scheduled for implantation of a CRT device, LVD was assessed by tissue Doppler
      imaging (TDI), defined as an electromechanical delay (EMD) difference of >=40 ms
      in 2 opposed left ventricular wall regions (septal vs. lateral, anterior vs.
      inferior). All-cause mortality, heart transplantation, or assist device
      implantation was defined as combined primary end point. Secondary end points were
      measures of reverse LV remodeling and of symptomatic improvement. RESULTS: Mean
      follow-up was 68 +/- 36 [range: 4-150] months. LVD at baseline was present in 308
      patients (61%). Of these, 24% reached the combined primary endpoint in contrast
      to 58% of patients without LVD (p < 0.001). Furthermore, patients with LVD showed
      pronounced improvement of all secondary end point parameters. In our cohort LVD
      was an independent predictor for outcome (hazard ratio [95% CI]: 0.30 [0.21
      0.42], p < 0.001). CONCLUSIONS: LVD at baseline as assessed by TDI is associated
      with a more pronounced clinical improvement and is a predictor for transplant
      free long-term survival in CRT recipients.

PMID- 23870641
TI  - The G263X MYBPC3 mutation is a common and low-penetrant mutation for hypertrophic
      cardiomyopathy in the region of Asturias (Northern Spain).

PMID- 23870642
TI  - Determinants of quality of life of patients with heart failure and iron
      deficiency treated with ferric carboxymaltose: FAIR-HF sub-analysis.
AB  - BACKGROUND: Heart failure (HF) is a burden to patients and health care systems.
      The objectives of HF treatment are to improve health related quality of life
      (HRQoL) and reduce mortality and morbidity. We aimed to evaluate determinants of
      health-related quality of life (HRQoL) in patients with iron deficiency and HF
      treated with intravenous (i.v.) iron substitution or placebo. METHODS: A
      randomised, double-blind, placebo-controlled trial (n = 459) in iron-deficient
      chronic heart failure (CHF) patients with or without anaemia studied clinical and
      HRQoL benefits of i.v. iron substitution using ferric carboxymaltose (FCM) over a
      24-week trial period. Multivariate analysis was carried out with various clinical
      variables as independent variables and HRQoL measures as dependent variables.
      RESULTS: Mean change from baseline of European Quality of Life - 5 Dimensions (EQ
      5D) (value set-based) utilities (on a 0 to 100 scale) at week 24 was 8.91 (i.v.
      iron) and 0.68 (placebo; p < 0.01). In a multivariate analysis excluding baseline
      HRQoL, a higher exercise tolerance and i.v. iron substitution positively
      influenced HRQoL, whereas impaired renal function and a history of stroke had a
      negative effect. The level of HRQoL was also influenced by country of residence.
      When baseline HRQoL was factored in, the multivariate model remained stable.
      CONCLUSION: In this study, i.v. iron substitution, exercise tolerance, stroke,
      country of residence and renal function influenced measures of HRQoL in patients
      with heart failure and iron deficiency.

PMID- 23870643
TI  - Myocardial mechanics for the early detection of cardiac sarcoidosis.

PMID- 23870644
TI  - Impaired baroreflex sensitivity and the risks of new-onset ambulatory
      hypertension, in an elderly population-based study.
AB  - BACKGROUND: Impairment of the autonomic nervous system activity may be involved
      in the development of hypertension. Yet the prognostic values of heart rate
      variability and baroreflex sensitivity in the risk of new-onset ambulatory
      hypertension have not been investigated. We sought to assess the relationship
      between heart rate variability and baroreflex sensitivity parameters and
      ambulatory hypertension in a community-dwelling elderly cohort. METHODS:
      Normotensive subjects were selected from the PROOF study cohort, including 1011
      subjects aged 65 years at baseline. The autonomic nervous system activity was
      assessed through 24-hour heart rate variability and 15-minute spontaneous
      baroreflex sensitivity at baseline. Incident hypertension was defined with the 24
      hour, day-time and night-time ambulatory blood pressure measurements and
      antihypertensive treatment use, at two-years of follow-up. RESULTS: At baseline,
      13.7% of subjects developed day-time hypertension, 18.2% developed night-time
      hypertension and 13.6% developed 24-hour hypertension. Reduced baroreflex
      sensitivity at baseline was associated with onset of hypertension after
      adjustment for blood pressure level, C-reactive protein levels and depression
      score (OR = 0.45 [0.23-0.86]). Indices of heart rate variability were not
      associated with hypertension onset. CONCLUSION: Baroreflex sensitivity may
      represent an intermediate goal for prevention of ambulatory hypertension at early
      stage.

PMID- 23870645
TI  - Day-by-day variability of self-measured blood pressure at home associated with
      cold pressor test norepinephrine, and heart rate variability in normotensive to
      moderate hypertensive.

PMID- 23870646
TI  - An appropriate use criterion is very important to reduce overuse for SPECT in
      coronary heart disease: economic burden in time of crises.

PMID- 23870647
TI  - Circulating microRNAs as potential biomarkers for the early diagnosis of acute
      myocardial infarction: promises and challenges.

PMID- 23870649
TI  - Anxiety and depression scales of patients with congenital heart disease: caution
      on 40 healthy controls as the reference population (reply).

PMID- 23870650
TI  - Effect of aspirin and warfarin therapy on thromboembolic events in patients with
      univentricular hearts and Fontan palliation.
AB  - BACKGROUND: Patients with univentricular hearts and Fontan palliation are at risk
      for thromboembolic complications. While aspirin and warfarin therapies are
      currently the mainstay of prophylaxis, controversy exists as to the optimal
      prevention strategy. METHODS: A cohort study was conducted on the New England
      registry of patients born in 1985 or earlier with Fontan surgery at Boston
      Children's Hospital, in order to assess and compare the effect of prophylactic
      aspirin and warfarin on incident thromboembolic events. RESULTS: A total of 210
      qualifying patients (49% male) underwent Fontan surgery at a median age of 8.5
      years: 48.6% had a right atrium to pulmonary artery anastomosis, 11% a right
      atrium to right ventricle conduit, 38.6% a lateral tunnel, and 1.9% an
      extracardiac conduit. No thromboembolic prophylaxis was prescribed to 50.0%,
      whereas 24.3% received aspirin, and 25.7% warfarin. In multivariate analyses,
      lack of aspirin or warfarin was associated with a significantly higher
      thromboembolic event rate when compared to therapy with either [hazard ratio 8.5,
      95% confidence interval (3.6-19.9), P < 0.001], with no difference between the
      two treatment strategies (P = 0.768). Twenty-year freedom from thromboemboli was
      86% versus 52% in patients with and without thromboprophylaxis, respectively.
      Other factors independently associated with thromboemboli were a low post
      operative cardiac index [hazard ratio 2.6, 95% confidence interval (1.2, 5.9)]
      and atrial fibrillation or flutter [hazard ratio 3.1, 95% confidence interval
      (1.2, 8.0)]. CONCLUSIONS: Prophylaxis with either aspirin or warfarin was
      associated with a significantly lower rate of incident thromboembolic events
      following Fontan palliation, with no difference between the two therapies.

PMID- 23870648
TI  - (-)-Epicatechin rich cocoa mediated modulation of oxidative stress regulators in
      skeletal muscle of heart failure and type 2 diabetes patients.
AB  - BACKGROUND: Type 2 diabetes (T2D) and heart failure (HF) are associated with high
      levels of skeletal muscle (SkM) oxidative stress (OS). Health benefits attributed
      to flavonoids have been ascribed to antioxidation. However, for flavonoids with
      similar antioxidant potential, end-biological effects vary widely suggesting
      other mechanistic venues for reducing OS. Decreases in OS may follow the
      modulation of key regulatory pathways including antioxidant levels (e.g.
      glutathione) and enzymes such as mitochondrial superoxide dismutase (SOD2) and
      catalase. METHODS: We examined OS-related alterations in SkM in T2D/HF patients
      (as compared vs. healthy controls) and evaluated the effects of three-month
      treatment with (-)-epicatechin (Epi) rich cocoa (ERC). To evidence Epi as the
      mediator of the improved OS profile we examined the effects of pure Epi (vs.
      water) on SkM OS regulatory systems in a mouse model of insulin resistance and
      contrasted results vs. normal mice. RESULTS: There were severe alterations in OS
      regulatory systems in T2D/HF SkM as compared with healthy controls. Treatment
      with ERC induced recovery in glutathione levels and decreases in the
      nitrotyrosilation and carbonylation of proteins. With treatment, key
      transcriptional factors translocate into the nucleus leading to increases in SOD2
      and catalase protein expression and activity levels. In insulin resistant mice,
      there were alterations in muscle OS and pure Epi replicated the beneficial
      effects of ERC found in humans. CONCLUSIONS: Major perturbations in SkM OS can be
      reversed with ERC in T2D/HF patients. Epi likely mediates such effects and may
      provide an effective means to treat conditions associated with tissue OS.

PMID- 23870651
TI  - Frequency-domain optical coherence tomography assessment of kissing-balloon
      effects in bifurcated coronary artery lesions undergoing provisional stenting.

PMID- 23870652
TI  - Characterization of recombinant human and bovine thyroid-stimulating hormone
      preparations by mass spectrometry and determination of their endotoxin content.
AB  - BACKGROUND: The TSH stimulation test to confirm canine hypothyroidism is commonly
      performed using a recombinant human TSH (rhTSH), as up to date, canine TSH is not
      yet commercially available. Limiting factors for the use of rhTSH are its high
      costs and occasional difficulties in product availability. Less expensive bovine
      TSH preparations (bTSH) purified from bovine pituitary glands are readily
      commercially available. The aim of this study was to evaluate two different bTSH
      products as alternative to rhTSH using mass spectrometry. RESULTS: More than 50
      proteins, including other pituitary hormones, bovine albumin, hemoglobin, and
      tissue proteins were identified in the bTSH preparations. In contrast, rhTSH
      proved to be a highly pure product. Significantly higher endotoxin levels could
      be detected in all bTSH products compared to the rhTSH. CONCLUSIONS: Both bTSH
      products are crude mixtures and therefore not an acceptable alternative to rhTSH.
      Their use should be discouraged to prevent unintended side effects.

PMID- 23870654
TI  - Balance circuit classes to improve balance among rehabilitation inpatients: a
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Impaired balance and mobility are common among rehabilitation
      inpatients. Poor balance and mobility lead to an increased risk of falling.
      Specific balance exercise has been shown to improve balance and reduce falls
      within the community setting. However few studies have measured the effects of
      balance exercises on balance within the inpatient setting. METHODS/DESIGN: A
      single centre, randomised controlled trial with concealed allocation, assessor
      blinding and intention-to-treat analysis. One hundred and sixty two patients
      admitted to the general rehabilitation ward at Bankstown-Lidcombe Hospital will
      be recruited. Eligible participants will have no medical contraindications to
      exercise and will be able to: fully weight bear; stand unaided independently for
      at least 30 seconds; and participate in group therapy sessions with minimal
      supervision. Participants will be randomly allocated to an intervention group or
      usual-care control group. Both groups will receive standard rehabilitation
      intervention that includes physiotherapy mobility training and exercise for at
      least two hours on each week day. The intervention group will also receive six 1
      hour circuit classes of supervised balance exercises designed to maximise the
      ability to make postural adjustments in standing, stepping and walking. The
      primary outcome is balance. Balance will be assessed by measuring the total time
      the participant can stand unsupported in five different positions; feet apart,
      feet together, semi-tandem, tandem and single-leg-stance. Secondary outcomes
      include mobility, self reported physical functioning, falls and hospital
      readmissions. Performance on the outcome measures will be assessed before
      randomisation and at two-weeks and three-months after randomisation by
      physiotherapists unaware of intervention group allocation. DISCUSSION: This study
      will determine the impact of additional balance circuit classes on balance among
      rehabilitation inpatients. The results will provide essential information to
      guide evidence-based physiotherapy at the study site as well as across other
      rehabilitation inpatient settings. TRIAL REGISTRATION: The protocol for this
      study is registered with the Australian New Zealand, Clinical Trials Registry:
      ACTRN=12611000412932.

PMID- 23870653
TI  - Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate
      species.
AB  - BACKGROUND: The process of generating raw genome sequence data continues to
      become cheaper, faster, and more accurate. However, assembly of such data into
      high-quality, finished genome sequences remains challenging. Many genome assembly
      tools are available, but they differ greatly in terms of their performance
      (speed, scalability, hardware requirements, acceptance of newer read
      technologies) and in their final output (composition of assembled sequence). More
      importantly, it remains largely unclear how to best assess the quality of
      assembled genome sequences. The Assemblathon competitions are intended to assess
      current state-of-the-art methods in genome assembly. RESULTS: In Assemblathon 2,
      we provided a variety of sequence data to be assembled for three vertebrate
      species (a bird, a fish, and snake). This resulted in a total of 43 submitted
      assemblies from 21 participating teams. We evaluated these assemblies using a
      combination of optical map data, Fosmid sequences, and several statistical
      methods. From over 100 different metrics, we chose ten key measures by which to
      assess the overall quality of the assemblies. CONCLUSIONS: Many current genome
      assemblers produced useful assemblies, containing a significant representation of
      their genes and overall genome structure. However, the high degree of variability
      between the entries suggests that there is still much room for improvement in the
      field of genome assembly and that approaches which work well in assembling the
      genome of one species may not necessarily work well for another.

PMID- 23870655
TI  - Epidermal hyperplasia induced by Raf-MAPK signaling requires Stat3 activation.
AB  - BACKGROUND: Raf is one of the downstream effectors of Ras GTPases, and plays a
      key role in regulating cell proliferation and differentiation through the
      activation of MAPK. We have previously demonstrated that temporal induction of
      Raf in the epidermis of K14-Raf:ER transgenic mice results in epidermal
      hyperplasia resembling squamous cell carcinoma and psoriasis. It has been
      demonstrated that epidermal Stat3 activation is required for psoriasis
      development, since keratinocyte-specific Stat3 activation in a mouse model
      elicits a psoriasis-like phenotype, which is reversed by inhibition of Stat3
      signaling. OBJECTIVE: The aim of this study was whether Stat3 signaling is
      involved in Raf-MAPK-dependent epidermal hyperplasia. METHODS: K14-Raf:ER
      transgenic mice, in which the 4-hydroxytamoxifen (4OHT)-responsive mutant
      estrogen receptor ligand binding domain-Raf fusion gene is expressed under
      control of the keratin 14 promoter, were mated with epidermis-specific Stat3 null
      mice (K5-Cre.Stat3(flox/flox)). K5-Cre.Stat3(flox/flox) mice were used to define
      the impact of Stat3 deficiency on Raf-induced epidermal hyperplasia. RESULTS:
      Over-expression of Raf by 4OHT treatment in K14-Raf:ER;K5-Cre.Stat3(flox/flox)
      mice greatly attenuated the epidermal hyperplasia and dermal cell infiltrates
      compared with K14-Raf:ER;K5-Cre.Stat3(flox/WT) mice. Also, up-regulation of
      psoriasis-associated cytokine profiles, including VEGF, was inhibited in the skin
      from K14-Raf:ER;K5-Cre.Stat3(flox/flox) mice following 4OHT treatment.
      CONCLUSION: These results clearly indicate that Raf-MAPK-dependent psoriatic-like
      epidermal hyperplasia requires Stat3 signaling in keratinocytes.

PMID- 23870656
TI  - Elevated circulating soluble interleukin-2 receptor in patients with non
      segmental vitiligo in North American.

PMID- 23870657
TI  - Observational, retrospective study of the effectiveness of 5-aminolevulinic acid
      in malignant glioma surgery in Spain (The VISIONA study).
AB  - OBJECTIVE: To assess effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan((r)))
      in patients treated for malignant glioma under typical daily practice conditions
      in Spain, using complete resection rate (CR) and progression free survival at 6
      months (PFS6). MATERIAL AND METHODS: Retrospective review of data from 18
      neurosurgery departments that were categorised as either using or not using 5
      ALA. The study included adult patients with suspected malignant gliomas for whom
      the intended treatment plan included complete resection followed by radiotherapy
      and chemotherapy with temozolomide. Postoperative MRI and clinical data
      representing at least 6 months were required for inclusion. Rates of CR and PFS6
      were compared between patients with 5-ALA treatment and those without. RESULTS:
      The study included 251 evaluable cases. CR and PFS6 rates were significantly
      higher in the group of patients treated surgically with 5-ALA: CR, 67% versus
      45%, p=.000; PFS6 for patients with grade IV tumours, 69% versus 48%; p=.002. The
      differences retained their significance and magnitude after adjusting for all
      covariates including age, functional status, and whether gliomas were located in
      eloquent areas. CONCLUSIONS: In this retrospective series, use of 5-ALA during
      habitual surgical procedures in Spain was associated with a higher complete
      resection rate for malignant glioma and increased PFS6 for grade iv glioma.

PMID- 23870658
TI  - Ultrasound imaging for diagnosis of plantar plate ruptures of the lesser
      metatarsophalangeal joints: a retrospective case series.
AB  - Tears of the plantar plate can be a source of significant forefoot pain, leading
      to alterations of foot function and gait. The objective of the present
      retrospective study was to further determine the value of ultrasound imaging in
      diagnosing plantar plate tears after clinical evaluation through a comparison of
      the ultrasound and intraoperative examination findings. Eight patients were
      identified who had undergone surgical intervention for a painful lesser
      metatarsophalangeal joint after ultrasound examination to diagnose a plantar
      plate pathologic entity. The intraoperative examination findings were used to
      calculate the sensitivity, specificity, and positive and negative predictive
      values of ultrasound in the diagnosis of plantar plate tears. The sensitivity and
      specificity of the ultrasound examination was 1 and 0.6, respectively. The
      positive and negative predictive value was 0.6 and 1, respectively. An ultrasound
      examination in the diagnosis of lesser metatarsophalangeal joint plantar plate
      tears displayed comparable sensitivity in identifying the pathologic features
      when compared with magnetic resonance imaging, with considerably less financial
      cost for the examination. 

PMID- 23870659
TI  - Clinical applications of T-wave alternans assessed during exercise stress testing
      and ambulatory ECG monitoring.
AB  - Analytical methods to measure T-wave alternans (TWA), a beat-to-beat fluctuation
      in the morphology of the ST-segment and T wave in the electrocardiogram (ECG),
      have been developed to address the unmet challenge of identifying individuals at
      increased risk for sudden cardiac death. Conventional noninvasive markers
      including left ventricular ejection fraction have significant limitations as many
      individuals who die suddenly have relatively preserved ventricular mechanical
      function. TWA is an attractive marker as it is closely linked to ECG
      heterogeneity and abnormalities in calcium handling, key factors in
      arrhythmogenesis. The objectives of this review are to summarize the clinical
      evidence supporting use of TWA in risk stratification and to discuss its current
      and potential applications in guiding device and medical therapy. 

PMID- 23870660
TI  - Prognostic implications of the J wave ECG patterns.

PMID- 23870661
TI  - New insights into the regulation of anthocyanin biosynthesis in fruits.
AB  - Anthocyanins are important health-promoting pigments that make a major
      contribution to the quality of fruits. The biosynthetic pathway leading to
      anthocyanins is well known and the key regulatory genes controlling the pathway
      have been isolated in many species. Recently, a considerable amount of new
      information has been gathered on the developmental and environmental regulation
      of anthocyanin biosynthesis in fruits, specifically the impact of regulation
      through light. New discoveries have begun to reveal links between the
      developmental regulatory network and the specific regulators of anthocyanin
      biosynthesis during fruit ripening. In this opinion article, a simplified model
      for the different regulatory networks involved with anthocyanin production in
      fruit is proposed. 

PMID- 23870662
TI  - Transcytosis shuts the door for an unwanted guest.
AB  - Penetration resistance is a well-described plant defense process, in which
      SOLUBLE N-ETHYLMALEIMIDE-SENSITIVE-FACTOR ATTACHMENT RECEPTOR (SNARE) proteins
      have essential roles in membrane fusion processes. Strong focal accumulation of
      these proteins at the site of attack by powdery mildew fungi has been considered
      important for their function. However, recent insight indicates that
      transcytosis, leading to the formation of exosomes, has an important role in this
      defense and, furthermore, that strong accumulation of these SNARE proteins with
      the exosomes is biologically irrelevant. These findings alter the established
      function of SNAREs in penetration resistance; therefore, in this opinion, we
      propose that PEN1 and its SNARE partners function on an endosome in their control
      of penetration resistance. 

PMID- 23870663
TI  - Highlights of the 16th annual scientific sessions of the Society for
      Cardiovascular Magnetic Resonance.
AB  - The 16th Annual Scientific Sessions of the Society for Cardiovascular Magnetic
      Resonance (SCMR) took place in San Francisco, USA at the end of January 2013.
      With a faculty of experts from across the world, this congress provided a wealth
      of insight into cutting-edge research and technological development. This review
      article intends to provide a highlight of what represented the most significant
      advances in the field of cardiovascular magnetic resonance (CMR) during this
      year's meeting. 

PMID- 23870664
TI  - Dancing the cell cycle two-step: regulation of yeast G1-cell-cycle genes by
      chromatin structure.
AB  - The chromatin structure at a promoter can define how a gene is regulated. Studies
      of two yeast genes expressed in the G1 phase of the cell cycle, HO and CLN2, have
      provided important paradigms for transcriptional regulation. Although the SBF
      (Swi4/Swi6 box factor) transcription factor activates both genes, the chromatin
      landscapes that regulate SBF binding are different. Specifically, the CLN2
      promoter is constitutively available for SBF binding, whereas HO has a complex
      two-step promoter in which chromatin changes in one region allow SBF to bind at a
      downstream location. These studies reveal the role of chromatin in defining the
      regulatory properties of promoters.

PMID- 23870665
TI  - Emerging roles of E3 ubiquitin ligases in autophagy.
AB  - Autophagy is an evolutionarily conserved intracellular catabolic process that
      delivers cytoplasmic components to lysosomes for degradation and recycling.
      Although originally considered to be a non-selective pathway, it is now
      recognized that autophagy is involved in selective processes, including the
      turnover of organelles, removal of protein aggregates, and elimination of
      intracellular pathogens. This specificity implies that cargo recognition and
      processing by the autophagy machinery are tightly regulated processes. In support
      of this, various forms of post-translational modification have been implicated in
      the regulation of autophagy, one of which is the ubiquitin-proteasome system.
      Here we review current understanding of the role of ubiquitylation in the control
      of autophagy.

PMID- 23870666
TI  - Physical activities at work and risk of musculoskeletal pain and its
      consequences: protocol for a study with objective field measures among blue
      collar workers.
AB  - BACKGROUND: Among blue-collar workers, high physical work demands are generally
      considered to be the main cause of musculoskeletal pain and work disability.
      However, current available research on this topic has been criticised for using
      self-reported data, cross-sectional design, insufficient adjustment for potential
      confounders, and inadequate follow-up on the recurrent and fluctuating pattern of
      musculoskeletal pain. Recent technological advances have provided possibilities
      for objective diurnal field measurements of physical activities and frequent
      follow-up on musculoskeletal pain.The main aim of this paper is to describe the
      background, design, methods, limitations and perspectives of the Danish Physical
      Activity cohort with Objective measurements (DPhacto) investigating the
      association between objectively measured physical activities capturing work and
      leisure time and frequent measurements of musculoskeletal pain among blue-collar
      workers. METHODS/DESIGN: Approximately 2000 blue-collar workers are invited for
      the study and asked to respond to a baseline questionnaire, participate in
      physical tests (i.e. muscle strength, aerobic fitness, back muscle endurance and
      flexibility), to wear accelerometers and a heart rate monitor for four
      consecutive days, and finally respond to monthly text messages regarding
      musculoskeletal pain and quarterly questionnaires regarding the consequences of
      musculoskeletal pain on work activities, social activities and work ability for a
      one-year follow-up period. DISCUSSION: This study will provide novel information
      on the association between physical activities at work and musculoskeletal pain.
      The study will provide valid and precise documentation about the relation between
      physical work activities and musculoskeletal pain and its consequences among blue
      collar workers.

PMID- 23870668
TI  - Clinical outcome in children with chronic granulomatous disease managed
      conservatively or with hematopoietic stem cell transplantation.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency
      characterized by serious infections and inflammation. It can be managed
      conservatively with prophylactic antimicrobial agents or curatively with
      hematopoietic stem cell transplantation (HSCT). In the United Kingdom and Ireland
      there are cohorts of children managed both conservatively and curatively.
      OBJECTIVES: This study aimed to compare clinical outcomes (mortality and
      morbidity) in children managed conservatively and curatively. METHODS: Children
      were identified from specialist centers and advertising through special interest
      groups. Clinical data were collected from medical records regarding infections,
      inflammatory complications and growth, other admissions, and curative treatment.
      Comparisons were made for patients not undergoing HSCT and patients after HSCT.
      RESULTS: Seventy-three living children were identified, 59 (80%) of whom were
      recruited. Five deceased children were also identified. Clinical information was
      available for 62 children (4 deceased). Thirty (48%) children had undergone HSCT.
      Children who did not undergo transplantation had 0.71 episodes of
      infection/admission/surgery per CGD life year (95% CI, 0.69-0.75 events per
      year). Post-HSCT children had 0.15 episodes of infection/admission/surgery per
      transplant year (95% CI, 0.09-0.21 events per year). The mean z score for height
      and body mass index (BMI) for age was significantly better in post-HSCT children.
      Survival in the non-HSCT group was 90% at age 15 years. Survival in the post-HSCT
      group was 90%. CONCLUSIONS: Children with CGD not undergoing transplantation have
      more serious infections, episodes of surgery, and admissions compared with post
      HSCT children. Children undergoing transplantation have better height for age.
      Survival is good at the end of the pediatric age range and also after HSCT.

PMID- 23870667
TI  - Selection of pfdhfr/pfdhps alleles and declining artesunate/sulphadoxine
      pyrimethamine efficacy against Plasmodium falciparum eight years after deployment
      in eastern Sudan.
AB  - BACKGROUND: Artesunate/sulphadoxine-pyrimethamine (AS/SP) has been the first-line
      treatment for falciparum malaria in Sudan since 2004. The impact of this
      combination on anti-malarial resistance-associated molecular markers has not been
      investigated. In this study, an evaluation of the efficacy and prevalence of drug
      resistance alleles (pfcrt, pfmdr1, pfdhfr and pfdhps) eight years after the
      adoption of AS/SP in eastern Sudan is reported. METHODS: A 28-day follow-up
      efficacy trial of AS/SP was conducted in eastern Sudan during the 2012
      transmission season. Blood smears were collected from patients on days 0, 1, 2,
      3, 7, 14, 21 and 28. Blood spots on filter paper were obtained pre-treatment and
      on the day the patient was parasite positive by microscopy. Genotyping of alleles
      was performed by qPCR (pfcrt 72-76 and pfmdr1 copy number) and direct sequencing
      of pfmdr1, pfdhfr and pfdhps. RESULTS: Sixty-three patients out of 68 (93%)
      completed the 28-day follow-up, adequate clinical, and parasitological response
      occurred in 90.5% and 85.3% of the patients in the per-protocol and intent-to
      treat analyses, respectively. PCR corrected per-protocol efficacy was 93.7%. The
      enrolment prevalence of pfcrt-CVMNK was 30.2% and pfmdr1-N86 was 40.3%. The
      pfmdr1 haplotype NFD occurred in 32.8% of pre-treatment samples and was
      significantly higher than previous reports (Fisher's exact p = 0.0001). The
      pfdhfr-51I/108N combination occurred in all sequenced isolates and 59R was
      observed in a single individual. pfdhps substitutions 436A, 437G, 540E, 581G and
      613S were observed at 7.8, 77.3, 76.9%, 33.8% and 0.0%, respectively. Treatment
      failures were associated with the pfdhps haplotype SGEGA at these five codons (OR
      7.3; 95% CI 0.65 - 368; p = 0.048). CONCLUSION: The decrease of CQR associated
      genotypes reflects the formal policy of complete removal of CQ in Sudan. However,
      the frequency of markers associated with SP failure is increasing in this study
      area and may be contributing to the treatment efficacy falling below 90%. Further
      monitoring of AS/SP efficacy and of post-treatment selection of pfdhfr and pfdhps
      alleles in vivo is required to inform future treatment guidelines.

PMID- 23870669
TI  - Profiling of human CD4+ T-cell subsets identifies the TH2-specific noncoding RNA
      GATA3-AS1.

PMID- 23870670
TI  - Efficacy of a short course of specific immunotherapy in patients with allergic
      rhinoconjunctivitis to ragweed pollen.
AB  - BACKGROUND: Specific immunotherapy acts to modify the underlying cause of
      allergic rhinoconjunctivitis. Addition of adjuvants, such as monophosphoryl lipid
      A (MPL), might allow for efficacious and safe treatment with only 4 injections
      administered preseasonally, which is in contrast to most available schedules
      requiring long injection courses. OBJECTIVE: The primary objective was to assess
      the clinical efficacy of Ragweed MATA MPL (short ragweed pollen allergoid
      adsorbed to L-Tyrosine + MPL) versus placebo in reducing allergic
      rhinoconjunctivitis symptoms caused by ragweed pollen in an environmental
      exposure chamber (EEC) 3 weeks after treatment. METHODS: This was a randomized,
      double-blind, placebo-controlled phase IIb study to evaluate the clinical
      efficacy and safety of Ragweed MATA MPL compared with placebo by using controlled
      ragweed pollen exposure in an EEC. Two hundred twenty-eight patients with a
      history of ragweed allergy and positive skin prick test responses to ragweed were
      randomized and received 4 weekly injections of active treatment or placebo. Total
      nasal and nonnasal symptom scores were obtained in the EEC before and after
      treatment. RESULTS: Mean improvement in total symptom scores in the Ragweed MATA
      MPL group was statistically significantly greater than in the placebo group
      (relative mean improvement of active vs placebo, 48%; P < .05; median
      improvement, 82%). The majority of adverse events (AEs) experienced by subjects
      were mild injection-site reactions. No severe systemic AEs or serious AEs
      occurred during the study. CONCLUSION: This study demonstrated that an ultrashort
      course of Ragweed MATA MPL is efficacious in reducing allergy symptoms in
      patients with seasonal allergic rhinitis and that it is well tolerated.

PMID- 23870671
TI  - Anhidrotic ectodermal dysplasia: a new mutation.

PMID- 23870672
TI  - CD39: a new surface marker of mouse regulatory gammadelta T cells.

PMID- 23870674
TI  - Prevention and control of rabies in an age of global travel: a review of travel-
      and trade-associated rabies events--United States, 1986-2012.
AB  - Rabies prevention and control efforts have been successful in reducing or
      eliminating virus circulation regionally through vaccination of specific
      reservoir populations. A notable example of this success is the elimination of
      canine rabies virus variant from the United States and many other countries.
      However, increased international travel and trade can pose risks for rapid, long
      distance movements of ill or infected persons or animals. Such travel and trade
      can result in human exposures to rabies virus during travel or transit and could
      contribute to the re-introduction of canine rabies variant or transmission of
      other viral variants among animal host populations. We present a review of travel
      and trade-associated rabies events that highlight international public health
      obligations and collaborative opportunities for rabies prevention and control in
      an age of global travel. Rabies is a fatal disease that warrants proactive
      coordination among international public health and travel industry partners (such
      as travel agents, tour companies and airlines) to protect human lives and to
      prevent the movement of viral variants among host populations. 

PMID- 23870673
TI  - The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced
      intestinal anaphylaxis.
AB  - BACKGROUND: Cytochrome P450, family 11, subfamily A, polypeptide 1 (Cyp11a1), a
      cytochrome P450 enzyme, is the first and rate-limiting enzyme in the
      steroidogenic pathway, converting cholesterol to pregnenolone. Cyp11a1 expression
      is increased in activated T cells. OBJECTIVES: We sought to determine the role of
      Cyp11a1 activation in the development of peanut allergy and TH cell functional
      differentiation. METHODS: A Cyp11a1 inhibitor, aminoglutethimide (AMG), was
      administered to peanut-sensitized and challenged mice. Clinical symptoms,
      intestinal inflammation, and Cyp11a1 levels were assessed. The effects of Cyp11a1
      inhibition on T(H)1, T(H)2, and T(H)17 differentiation were determined. Cyp11a1
      gene silencing was performed with Cyp11a1-targeted short hairpin RNA. RESULTS:
      Peanut sensitization and challenge resulted in diarrhea, inflammation, and
      increased levels of Cyp11a1, IL13, and IL17A mRNA in the small intestine.
      Inhibition of Cyp11a1 with AMG prevented allergic diarrhea and inflammation.
      Levels of pregnenolone in serum were reduced in parallel. AMG treatment decreased
      IL13 and IL17A mRNA expression in the small intestine without affecting Cyp11a1
      mRNA or protein levels. In vitro the inhibitor decreased IL13 and IL17A mRNA and
      protein levels in differentiated T(H)2 and T(H)17 CD4 T cells, respectively,
      without affecting GATA3, retinoic acid-related orphan receptor gammat
      (RORgammat), or T(H)1 cells and IFNG and T-bet expression. Short hairpin RNA
      mediated silencing of Cyp11a1 in polarized T(H)2 CD4 T cells significantly
      decreased pregnenolone and IL13 mRNA and protein levels. CONCLUSION: Cyp11a1
      plays an important role in the development of peanut allergy, regulating peanut
      induced allergic responses through effects on steroidogenesis, an essential
      pathway in T(H)2 differentiation. Cyp11a1 thus serves as a novel target in the
      regulation and treatment of peanut allergy.

PMID- 23870676
TI  - Culture, salience, and psychiatric diagnosis: exploring the concept of cultural
      congruence & its practical application.
AB  - INTRODUCTION: Cultural congruence is the idea that to the extent a belief or
      experience is culturally shared it is not to feature in a diagnostic judgement,
      irrespective of its resemblance to psychiatric pathology. This rests on the
      argument that since deviation from norms is central to diagnosis, and since what
      counts as deviation is relative to context, assessing the degree of fit between
      mental states and cultural norms is crucial. Various problems beset the cultural
      congruence construct including impoverished definitions of culture as religious,
      national or ethnic group and of congruence as validation by that group. This
      article attempts to address these shortcomings to arrive at a cogent construct.
      RESULTS: The article distinguishes symbolic from phenomenological conceptions of
      culture, the latter expanded upon through two sources: Husserl's phenomenological
      analysis of background intentionality and neuropsychological literature on
      salience. It is argued that culture is not limited to symbolic presuppositions
      and shapes subjects' experiential dispositions. This conception is deployed to re
      examine the meaning of (in)congruence. The main argument is that a significant,
      since foundational, deviation from culture is not from a value or belief but from
      culturally-instilled experiential dispositions, in what is salient to an
      individual in a particular context. CONCLUSION: Applying the concept of cultural
      congruence must not be limited to assessing violations of the symbolic order and
      must consider alignment with or deviations from culturally-instilled experiential
      dispositions. By virtue of being foundational to a shared experience of the
      world, such dispositions are more accurate indicators of potential vulnerability.
      Notwithstanding problems of access and expertise, clinical practice should aim to
      accommodate this richer meaning of cultural congruence.

PMID- 23870677
TI  - Synthesis and evaluation of [11C]MMPIP as a potential radioligand for imaging of
      metabotropic glutamate 7 receptor in the brain.
AB  - BACKGROUND: Metabotropic glutamate 7 (mGlu7) receptor is a crucial target protein
      for the development of pharmaceuticals against central nervous system disorders.
      In the present study, we synthesized [11C]MMPIP, a putative radioligand for mGlu7
      (binding constant KB = 30 nM), and evaluated its potential for imaging of mGlu7
      via in vitro and in vivo techniques. METHODS: [11C]MMPIP was synthesized by the
      reaction of phenol precursor 3 with [11C]CH3I. In vitro autoradiography using
      [11C]MMPIP was performed on rat brain sections. To determine in vitro specific
      binding of [11C]MMPIP with mGlu7, a blocking study was conducted by co-incubation
      with excess AMN082, a selective antagonist for mGlu7, or unlabeled MMPIP.
      Positron emission tomography (PET) studies and ex vivo metabolite analysis were
      carried out on rat brains. RESULTS: [11C]MMPIP was obtained with two specific
      activity (SA) levels of average 58 (conventional) and 3,800 (high SA) GBq/MUmol,
      respectively. High radioactive signals derived from conventional [11C]MMPIP in
      the in vitro autoradiography were seen in the thalamus, medulla oblongata, and
      striatum, corresponding with comprehensive brain distributions of mGlu7. Co
      incubation with ANM082 or unlabeled MMPIP reduced the radioactive signals in the
      brain sections, respectively. In the PET studies with [11C]MMPIP, no specific
      uptake relative to mGlu7 was found in the examined brain regions. CONCLUSION:
      Despite in vitro specific binding of [11C]MMPIP with mGlu7, visualization of
      mGlu7 in the living brain using PET was not successful. Development of new ligand
      candidates with higher affinity for mGlu7 is necessary.

PMID- 23870678
TI  - Heritability of acquiescence bias and item keying response style associated with
      the HEXACO personality scale.
AB  - The current research investigates the heritability of two of the most common
      response styles: acquiescence bias (tendency to agree or disagree with survey
      items regardless of the items' actual content) and item keying (differential
      responding related to the use of regular- and reverse-keyed items). We estimated
      response styles from a common personality measure (HEXACO) and examined the
      heritability of each with univariate genetics analyses. The results show item
      keying effect was heritable but acquiescence bias was not. Neither response style
      was strongly influenced by the shared environment of the twins. Unique
      environmental effects were found to be substantial for response styles. The
      current findings have important implications for future research of response
      behaviors that are often overlooked by behavioral geneticists. 

PMID- 23870679
TI  - Key informants' perspectives of implementing chromosomal microarrays into
      clinical practice in Australia.
AB  - High-resolution genomic tests have the potential to revolutionize healthcare by
      vastly improving mutation detection. The use of chromosomal microarray (CMA)
      represents one of the earliest examples of these new genomic tests being
      introduced and disseminated in the clinic. While CMA has clear advantages over
      traditional karyotyping in terms of mutation detection, little research has
      investigated the process by which CMA was implemented in clinical settings.
      Fifteen key informants, six clinicians, and nine laboratory scientists from four
      Australian states were interviewed about their experiences during and in the time
      since CMA was adopted for clinical use. Participants discussed challenges such as
      result interpretation and communication. Strengths were also highlighted,
      including the collaborative approaches of some centers. Clinical experiences and
      opinions can inform larger studies with a range of stakeholders, including
      patients. The historical perspectives from this retrospective study can be
      helpful in guiding the implementation of future genomic technologies such as
      whole exome/genome sequencing. 

PMID- 23870680
TI  - Objective monitoring of mTOR inhibitor therapy by three-dimensional facial
      analysis.
AB  - With advances in therapeutics for rare, genetic and syndromic diseases, there is
      an increasing need for objective assessments of phenotypic endpoints. These
      assessments will preferentially be high precision, non-invasive, non-irradiating,
      and relatively inexpensive and portable. We report a case of a child with an
      extensive lymphatic vascular malformation of the head and neck, treated with an
      mammalian target of Rapamycin (mTOR) inhibitor that was assessed using 3D facial
      analysis. This case illustrates that this technology is prospectively a cost
      effective modality for treatment monitoring, and it supports that it may also be
      used for novel explorations of disease biology for conditions associated with
      disturbances in the mTOR, and interrelated, pathways. 

PMID- 23870684
TI  - HGSA DNA day essay contest winner 60 years on: still coding for cutting-edge
      science.
AB  - MESSAGE FROM THE EDUCATION COMMITTEE: In 2013, the Education Committee of the
      Human Genetics Society of Australasia (HGSA) established the DNA Day Essay
      Contest in Australia and New Zealand. The contest was first established by the
      American Society of Human Genetics in 2005 and the HGSA DNA Day Essay Contest is
      adapted from this contest via a collaborative partnership. The aim of the contest
      is to engage high school students with important concepts in genetics through
      literature research and reflection. As 2013 marks the 60th anniversary of the
      discovery of the double helix of DNA by James Watson and Francis Crick and the
      10th anniversary of the first sequencing of the human genome, the essay topic was
      to choose either of these breakthroughs and explain its broader impact on
      biotechnology, human health and disease, or our understanding of basic genetics,
      such as genetic variation or gene expression. The contest attracted 87 entrants
      in 2013, with the winning essay authored by Patrick Yates, a Year 12 student from
      Melbourne High School. Further details about the contest including the names and
      schools of the other finalists can be found at http://www.hgsa-essay.net.au/. The
      Education Committee would like to thank all the 2013 applicants and encourage
      students to enter in 2014.

PMID- 23870685
TI  - Switched-at-birth twins in the Canary Islands: revisited.

PMID- 23870688
TI  - Academic integrity in the online learning environment for health sciences
      students.
AB  - BACKGROUND: The online learning environment not only affords accessibility to
      education for health sciences students, but also poses challenges to academic
      integrity. Technological advances contribute to new modes of academic dishonesty,
      although there may be a lack of clarity regarding behaviors that constitute
      academic dishonesty in the online learning environment. OBJECTIVE: To evaluate an
      educational intervention aimed at increasing knowledge and improving attitudes
      about academic integrity in the online learning environment among health sciences
      students. DESIGN: A quasi-experimental study was conducted using a survey of
      online learning knowledge and attitudes with strong reliability that was
      developed based on a modified version of a previously developed information
      technology attitudes rating tool with an added knowledge section based on the
      academic integrity statement. SETTING: Blended-learning courses in a university
      health sciences center. PARTICIPANTS: 355 health sciences students from various
      disciplines, including nursing, pre-medical, and exercise physiology students,
      161 in the control group and 194 in the intervention group. METHOD: The survey of
      online learning knowledge and attitudes (SOLKA) was used in a pre-post test study
      to evaluate the differences in scores between the control group who received the
      standard course introduction and the intervention group who received an enhanced
      educational intervention about academic integrity during the course introduction.
      RESULTS: Post-intervention attitude scores were significantly improved compared
      to baseline scores for the control and intervention groups, indicating a positive
      relationship with exposure to the information, with a greater improvement among
      intervention group participants (p<0.001). There was a significant improvement in
      the mean post-intervention knowledge score of the intervention group compared to
      the control group (p=0.001). CONCLUSION: Recommendations are provided for
      instructors in promoting academic integrity in the online environment. Emphasis
      should be made about the importance of academic integrity in the online learning
      environment in preparation for professional behavior in the technologically
      advancing health sciences arena.

PMID- 23870689
TI  - Factors affecting the job satisfaction levels and quit intentions of academic
      nurses.
AB  - The descriptively designed study was conducted in order to determine academic
      nurses' job satisfaction levels, intention of leaving job and effective reasons.
      The study was implemented in 10 nursing schools offering postgraduate and
      doctoral education in Turkey, and data was collected from academics working in
      these schools who agreed to participate in the study. After obtaining the
      required approval from the ethics committees and institutional permissions, data
      was collected from 248 academic nurses using a personal information form and a
      "Job Satisfaction Scale" between June 2009 and January 2010. The data was
      analyzed by frequency and percentage distribution, using Cronbach's Alpha
      coefficient, ANOVA, Qui-Square and Tukey's HSD test for advanced analysis methods
      with SPSS 11.5 statistics packet software. This study concludes that academic
      nurses are moderately satisfied with their jobs. In addition, job satisfaction
      was found to be lower among research assistants, assistant professors, nurses
      with less than 10 years of academic experience, nurses who have completed their
      doctorate dissertations, or who are working on appointment or contract basis.

PMID- 23870690
TI  - Deviations from venous blood specimen collection guideline adherence among senior
      nursing students.
AB  - BACKGROUND: Despite considerable efforts to increase patient safety by supporting
      the use of best practice medical and nursing guidelines by healthcare staff,
      adherence is often suboptimal. Swedish nurses often deviate from venous blood
      specimen collection (VBSC) guideline adherence. We assessed the adherence to
      national VBSC guidelines among senior nursing students. METHODS: We conducted a
      cross-sectional, self-reported questionnaire survey among 101 out of 177 senior
      nursing students consisting of web-based students in their fifth semester and
      campus-based students in their fifth or sixth semester out of six. In regard to
      the VBSC procedures, we asked about adherence to the patient identification, test
      request handling, and test tube labelling protocols that the students had learned
      during their second semester and practiced thereafter. RESULTS: Guideline
      adherence to patient identification was reported by 81%, test request handling by
      74%, and test tube labelling by 2% of the students. Students with no prior
      healthcare education reported to a higher extent that they operated within the
      guidelines regarding labelling the test tube before entering the patient's room
      compared to students with prior healthcare education. Using multiple logistic
      regression analysis, we found that fifth semester web-based program students
      adhered better to VBSC guidelines regarding comparing patient ID/test
      request/tube label compared to campus-based students. CONCLUSIONS: Senior nursing
      students were found to adhere to VBSC guidelines to a similar extent as
      registered nurses and other hospital ward staff in clinical healthcare. Thus
      student adherence to VBSC guidelines had deteriorated since their basic training
      in the second semester, and this can impact patient safety during
      university/clinical studies. The results of our study have implications for
      nursing practice education.

PMID- 23870691
TI  - The effects of a hardiness educational intervention on hardiness and perceived
      stress of junior baccalaureate nursing students.
AB  - Baccalaureate nursing education is stressful. The stress encompasses a range of
      academic, personal, clinical, and social reasons. A hardiness educational
      program, a tool for stress management, based on theory, research, and practice,
      exists to enhance the attitudes and coping strategies of hardiness (Maddi, 2007;
      Maddi et al., 2002). Research has shown that students who completed the hardiness
      educational program, subsequently improved in grade point average (GPA), college
      retention rates, and health (Maddi et al., 2002). Little research has been done
      to explore the effects of hardiness education with junior baccalaureate nursing
      students. Early identification of hardiness, the need for hardiness education, or
      stress management in this population may influence persistence in and completion
      of a nursing program (Hensel and Stoelting-Gettelfinger, 2011). Therefore, the
      aims were to determine if an increase in hardiness and a decrease in perceived
      stress in junior baccalaureate nursing students occurred in those who
      participated in a hardiness intervention. The application of the Hardiness Model
      and the Roy Adaptation Model established connections and conceptual collaboration
      among stress, stimuli, adaptation, and hardi-coping. A quasi-experimental non
      equivalent control group with pre-test and post-test was used with a convenience
      sample of full-time junior level baccalaureate nursing students. Data were
      collected from August 2011 to December 2011. Results of statistical analyses by
      paired t-tests revealed that the hardiness intervention did not have a
      statistically significant effect on increasing hardiness scores. The hardiness
      intervention did have a statistically significant effect on decreasing perceived
      stress scores. The significant decrease in perceived stress was congruent with
      the Hardiness Model and the Roy Adaptation Model. Further hardiness research
      among junior baccalaureate nursing students, utilizing the entire hardiness
      intervention, was recommended. 

PMID- 23870692
TI  - The opportunity to collaborate increases preschoolers' motivation for challenging
      tasks.
AB  - Collaborating on challenging endeavors is a foundation of human society. Recent
      research suggests that young children are not only motivated to cooperate with
      others-for instance, to help others accomplish their goals-but may also be
      motivated to collaborate with others-to pursue shared goals. However, a primary
      reason why collaboration is so important is because opportunities to collaborate
      can bring people together to work hard to overcome challenges. Two studies (N=70)
      tested whether the collaborative nature of an activity itself can cause
      preschoolers to enjoy challenging tasks more and to persist longer on them. To
      isolate the psychological feeling of collaboration, we tested this hypothesis by
      manipulating purely psychological cues of collaboration; in all cases, children
      worked while physically alone. Both studies found that such cues substantially
      increased preschoolers' motivation on a challenging puzzle, including their
      persistence on and liking for the puzzle, relative to two non-collaborative
      control conditions. We suggest that an early emerging drive to engage in shared
      collaborative activities leads children to find collaborative activities to be
      intrinsically motivating. This may represent an important basis of motivation as
      children embark on formal schooling. 

PMID- 23870693
TI  - Epidemiological study of air filtration systems for preventing PRRSV infection in
      large sow herds.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is the most
      economically significant pathogen in the US swine industry. Aerosol transmission
      among herds is a major concern in pig dense regions and filtration of incoming
      air, in combination with standard biosecurity procedures, has been demonstrated
      to prevent transmission of PRRSV into susceptible herds. To quantify the impact
      of air filtration on reducing risk of PRRSV outbreaks, we compared the incidence
      rate of new PRRSV introductions in 20 filtered and 17 non-filtered control sow
      herds in a swine dense region of North America during a 7 year study period.
      Events of novel virus introduction were ascertained by phylogenetic analysis of
      PRRSV ORF5 gene sequences. Putative new viruses were defined as exogenous
      (introduced) based on ORF5 nucleotide sequence differences compared to previous
      farm isolates. The influence of sequence difference cut-off values ranging from 2
      to 10% on case definition and relative risk were evaluated. Non-filtered farms
      incurred about 0.5 outbreaks per year, with a seasonal increase in risk in cooler
      periods. Baseline risk, prior to filtration, in treatment farms was approximately
      0.75 per year, approximately 50% higher than in control farms. Air filtration
      significantly reduced risk of PRRSV introduction events to 0.06-0.22 outbreaks
      per year, depending on the cut-off values used to classify a virus isolate as new
      to the herd. Overall, air filtration led to an approximately 80% reduction in
      risk of introduction of novel PRRSV, indicating that on large sow farms with good
      biosecurity in swine-dense regions, approximately four-fifths of PRRSV outbreaks
      may be attributable to aerosol transmission.

PMID- 23870694
TI  - Single-incision thoracoscopic lobectomy and segmentectomy with radical lymph node
      dissection.
AB  - BACKGROUND: Reports of single-incision thoracoscopic lobectomy and segmentectomy
      are rare. In this article, we present our experience with single-incision
      thoracoscopic lobectomy and segmentectomy and radical mediastinal lymph node
      dissection. METHODS: Nineteen patients with early-stage malignancy or benign lung
      disease were treated with single-incision thoracoscopic lobectomy and
      segmentectomy at our institution between November 2010 and May 2012. The surgical
      approach began with a single incision at the fifth or sixth intercostal space at
      the anterior axillary line. A 10-mm video camera and working instruments were
      used at the same time in this incision site throughout the surgery. The
      perioperative variables and outcomes were collected and analyzed retrospectively.
      RESULTS: For the 19 patients included in the final analysis, 14 lobectomies and 5
      segmentectomies were performed successfully without need for conversion. Among
      the 19 patients who underwent single-port video-assisted thoracoscopic surgery
      (VATS), 15 cases of cancer and 4 cases of benign pulmonary disease were noted.
      The mean operative time was 156+/-46 minutes, and the median number of lymph
      nodes retrieved was 22.9+/-9.8. Average blood loss was 38.4+/-25.9 mL. There were
      no deaths 30 days after surgery, and 2 cases of atelectasis were observed.
      CONCLUSIONS: Single-port VATS lobectomy and segmentectomy is safe and feasible
      for selected patients.

PMID- 23870695
TI  - Medium term outcomes of transapical aortic valve implantation: results from the
      Italian Registry of Trans-Apical Aortic Valve Implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been proposed as a
      therapeutic option for high-risk or inoperable patients with severe symptomatic
      aortic valve stenosis. The aim of this multicenter study was to assess early and
      medium term outcomes of transapical aortic valve implantation (TA-TAVI). METHODS:
      From April 2008 through June 2012, a total of 774 patients were enrolled in the
      Italian Registry of Trans-Apical Aortic Valve Implantation (I-TA). Twenty-one
      centers were included in the I-TA registry. Outcomes were also analyzed according
      to the impact of the learning curve (first 50% cases versus second 50% cases of
      each center) and of the procedural volume (high-volume versus low-volume
      centers). RESULTS: Mean age was 81.0+/-6.7 years, mean logistic European System
      for Cardiac Operative Risk Evaluation (EuroSCORE) I, EuroSCORE II, and The
      Society of Thoracic Surgeons risk score were 25.6%+/-16.3%, 9.4%+/-11.0%, and
      10.6%+/-8.5%, respectively. Median follow-up was 12 months (range, 1 to 44).
      Thirty-day mortality was 9.9% (77 patients). Overall 1-, 2-, and 3-year survival
      was 81.7%+/-1.5%, 76.1%+/-1.9%, and 67.6%+/-3.2%, respectively. Thirty-day
      mortality of the first 50% patients of each center was higher when compared with
      the second half (p=0.04) but 3-year survival was not different (p=0.64).
      Conversely, 30-day mortality at low-volume centers versus high-volume centers was
      similar (p=0.22). At discharge, peak and mean transprosthetic gradients were
      21.0+/-10.3 mm Hg and 10.2+/-4.1 mm Hg, respectively. These values remained
      stable 12 and 24 months after surgery. CONCLUSIONS: Transapical TAVI provides
      good results in terms of early and midterm clinical and hemodynamic outcomes.
      Thus it appears to be a safe and effective alternative treatment for patients who
      are inoperable or have high surgical risk.

PMID- 23870696
TI  - Preoperative serum soluble receptor activator of nuclear factor-kappaB ligand and
      osteoprotegerin predict postoperative atrial fibrillation in patients undergoing
      cardiac valve surgery.
AB  - BACKGROUND: Postoperative atrial fibrillation (POAF), a frequent complication
      after cardiac surgery, causes morbidity and prolongs hospitalization. A
      significant association between circulating osteoprotegerin concentration and
      atrial fibrillation incidence had been identified. Osteoprotegerin/receptor
      activator of nuclear factor-kappaB/receptor activator of nuclear factor-kappaB
      ligand (RANKL) axis may also contribute to the development and progression of AF.
      Herein we sought to determine whether preoperative serum soluble RANKL and
      osteoprotegerin and soluble RANKL/osteoprotegerin ratio are associated with the
      incidence of POAF in cardiac surgery patients. METHODS: We enrolled 154 patients
      with preoperative sinus rhythm undergoing isolated cardiac valve surgery.
      Preoperative venous blood samples were obtained for measurement of serum soluble
      RANKL and osteoprotegerin. The POAF was defined as the characteristic arrhythmia
      lasting for at least 30 seconds before discharge. Comparison was made between
      patients without episode of POAF (sinus rhythm group, n=93) and patients
      experiencing POAF (atrial fibrillation group, n=61). RESULTS: Serum levels of
      soluble RANKL and osteoprotegerin and soluble RANKL/osteoprotegerin ratio were
      significantly higher in the atrial fibrillation group than the sinus rhythm
      group. In multivariate survival regression, C-reactive protein, ejection
      fraction, left and right atrial diameters, preoperative use of beta-blocker,
      duration of ventilation, particularly serum soluble RANKL level, and soluble
      RANKL/osteoprotegerin ratio independently predicted POAF. According to receiver
      operating characteristic curve analysis, the best threshold values of serum
      soluble RANKL level and soluble RANKL/osteoprotegerin ratio for predicting POAF
      were 3.62 pmol/L and 0.51, respectively. CONCLUSIONS: Elevated preoperative serum
      soluble RANKL level and soluble RANKL/osteoprotegerin ratio are independent
      predictors for POAF in patients undergoing cardiac valve surgery. These findings
      have important implications for identifying patients at higher risk of POAF who
      could be considered for prophylactic therapy.

PMID- 23870697
TI  - Real-time cardiovascular magnetic resonance subxiphoid pericardial access and
      pericardiocentesis using off-the-shelf devices in swine.
AB  - BACKGROUND: Needle access or drainage of pericardial effusion, especially when
      small, entails risk of bystander tissue injury or operator uncertainty about
      proposed trajectories. Cardiovascular magnetic resonance (CMR) might allow
      enhanced imaging guidance. METHODS AND RESULTS: We used real-time CMR to guide
      subxiphoid pericardial access in naive swine using commercial 18G titanium
      puncture needles, which were exchanged for pericardial catheters. To test the
      value of CMR needle pericardiocentesis, we also created intentional pericardial
      effusions of a range of volumes, via a separate transvenous-transatrial catheter.
      We performed these procedures in 12 animals. CONCLUSIONS: CMR guided
      pericardiocentesis is attractive because the large field of view and soft tissue
      imaging depict global anatomic context in arbitrary planes, and allow the
      operator to plan trajectories that limit inadvertent bystander tissue injury.
      More important, CMR provides continuous visualization of the needle and target
      throughout the procedure. Using even passive needle devices, CMR enabled rapid
      pericardial needle access and drainage. We believe this experience supports
      clinical testing of real-time CMR guided needle access or drainage of the
      pericardial space. We suspect this would be especially helpful in "difficult"
      pericardial access, for example, in distorted thoracic anatomy or loculated
      effusion.

PMID- 23870699
TI  - Chemical mechanisms involved during the biosynthesis of tropolones.
AB  - Tropolones are seven-membered aromatic rings which feature in the core of several
      important bioactive natural products including colchicine and stipitatic acid.
      Studies of their biosynthesis over nearly 70 years have revealed four parallel
      routes from polyketide, terpene, alkaloid and shikimate precursors, but the key
      steps all involve ring expansion of an alkylated 6-membered ring. Recent studies
      in fungi have revealed details of the individual chemical steps at the molecular
      level, but detailed molecular biosynthetic pathways in other organisms remain
      obscure. 

PMID- 23870698
TI  - Phosphonate biosynthesis and catabolism: a treasure trove of unusual enzymology.
AB  - Natural product biosynthesis has proven a fertile ground for the discovery of
      novel chemistry. Herein we review the progress made in elucidating the
      biosynthetic pathways of phosphonate and phosphinate natural products such as the
      antibacterial compounds dehydrophos and fosfomycin, the herbicidal
      phosphinothricin-containing peptides, and the antimalarial compound FR-900098. In
      each case, investigation of the pathway has yielded unusual, and often
      unprecedented, biochemistry. Likewise, recent investigations have uncovered novel
      ways to cleave the CP bond to yield phosphate under phosphorus starvation
      conditions. These include the discovery of novel oxidative cleavage of the CP
      bond catalyzed by PhnY and PhnZ as well as phosphonohydrolases that liberate
      phosphate from phosphonoacetate. Perhaps the crown jewel of phosphonate
      catabolism has been the recent resolution of the longstanding problem of the C-P
      lyase responsible for reductively cleaving the CP bond of a number of different
      phosphonates to release phosphate. Taken together, the strides made on both
      metabolic and catabolic fronts illustrate an array of fascinating biochemistry. 

PMID- 23870700
TI  - Design, synthesis and pharmacological evaluation of (E)-3,4-dihydroxy styryl
      sulfonamides derivatives as multifunctional neuroprotective agents against
      oxidative and inflammatory injury.
AB  - A novel class of (E)-3,4-dihydroxy styryl sulfonamides and their 3,4-diacetylated
      derivatives as caffeic acid phenethyl ester (CAPE) analogs was designed and
      prepared for improving stability and solubility of the lead compound. Their
      neuroprotective properties were assessed by several models. The results showed
      that target compounds displayed positive free radical quenching abilities,
      superior to that of CAPE. Compounds 6j-k and 7j-k demonstrated remarkable
      protection effects against damage induced by hydrogen peroxide which were
      apparently stronger than that of CAPE. Most of target compounds could inhibit
      nitric oxide production. Additionally, target compounds showed high blood-brain
      barrier permeability. 

PMID- 23870702
TI  - A decision rule to aid selection of patients with abdominal sepsis requiring a
      relaparotomy.
AB  - BACKGROUND: Accurate and timely identification of patients in need of a
      relaparotomy is challenging since there are no readily available strongholds. The
      aim of this study is to develop a prediction model to aid the decision-making
      process in whom to perform a relaparotomy. METHODS: Data from a randomized trial
      comparing surgical strategies for relaparotomy were used. Variables were selected
      based on previous reports and common clinical sense and screened in a univariable
      regression analysis to identify those associated with the need for relaparotomy.
      Variables with the strongest association were considered for the prediction model
      which was constructed after backward elimination in a multivariable regression
      analysis. The discriminatory capacity of the model was expressed with the area
      under the curve (AUC). A cut-off analysis was performed to illustrate the
      consequences in clinical practice. RESULTS: One hundred and eighty-two patients
      were included; 46 were considered cases requiring a relaparotomy. A prediction
      model was build containing 6 variables. This final model had an AUC of 0.80
      indicating good discriminatory capacity. However, acceptable sensitivity would
      require a low threshold for relaparotomy leading to an unacceptable rate of
      negative relaparotomies (63%). Therefore, the prediction model was incorporated
      in a decision rule were the interval until re-assessment and the use of Computed
      Tomography are related to the outcome of the model. CONCLUSIONS: To construct a
      prediction model that will provide a definite answer whether or not to perform a
      relaparotomy seems a utopia. However, our prediction model can be used to
      stratify patients on their underlying risk and could guide further monitoring of
      patients with abdominal sepsis in order to identify patients with suspected
      ongoing peritonitis in a timely fashion.

PMID- 23870703
TI  - Genetic variation comparison of 15 autosomal STR loci in an immigrant population
      living in the UK (British Pakistanis) with an ancestral origin population from
      Pakistan.

PMID- 23870704
TI  - Fast selection of maribavir resistant cytomegalovirus in a bone marrow transplant
      recipient.
AB  - BACKGROUND: Human cytomegalovirus infections are still significant causes of
      morbidity and mortality in transplant recipients. The use of antiviral agents is
      limited by toxicity and evolving resistance in immunocompromised patients with
      ongoing viral replication during therapy. Here, we present the first documented
      case of genotypic resistance against maribavir in a bone marrow transplant (BMT)
      recipient. CASE PRESENTATION: The female 13-year-old patient was suffering from a
      refractory cytopenia. Ganciclovir, foscarnet, cidofovir, leflunomide and
      maribavir, an inhibitor of the cytomegalovirus UL97 protein, were administered to
      treat a therapy-resistant cytomegalovirus infection. Viral mutations conferring
      resistance against nucleotide and pyrophosphate analogs as well as maribavir
      (MBV) have evolved sequentially. Particularly, impressive was the fast emergence
      of multiple mutations T409M, H411Y and H411N conferring maribavir resistance
      after less than 6 weeks. CONCLUSION: We describe the fast emergence of
      cytomegalovirus variants with different maribavir resistance associated mutations
      in a bone marrow transplant recipient treated with MBV 400 mg p.o. twice per day.
      The results suggest that a high virus load permitted a selection of several but
      distinct therapy-resistant HCMV mutants. Since a phase II study with MBV is
      intended for the treatment of resistant or refractory HCMV infections in
      transplant recipients this has to be kept in mind in patients with high viral
      loads during therapy (NCT01611974).

PMID- 23870705
TI  - Schizophrenia.
AB  - INTRODUCTION: The lifetime prevalence of schizophrenia is approximately 0.7% and
      incidence rates vary between 7.7 and 43.0 per 100,000; about 75% of people have
      relapses and continued disability, and one third fail to respond to standard
      treatment. Positive symptoms include auditory hallucinations, delusions, and
      thought disorder. Negative symptoms (demotivation, self-neglect, and reduced
      emotion) have not been consistently improved by any treatment. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of drug treatments for positive,
      negative, or cognitive symptoms of schizophrenia? What are the effects of drug
      treatments in people with schizophrenia who are resistant to standard
      antipsychotic drugs? What are the effects of interventions to improve adherence
      to antipsychotic medication in people with schizophrenia? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to May 2010
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      51 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions:
      amisulpride, chlorpromazine, clozapine, depot haloperidol decanoate, haloperidol,
      olanzapine, pimozide, quetiapine, risperidone, sulpiride, ziprasidone, zotepine,
      aripiprazole, sertindole, paliperidone, flupentixol, depot flupentixol decanoate,
      zuclopenthixol, depot zuclopenthixol decanoate, behavioural therapy, clozapine,
      compliance therapy, first-generation antipsychotic drugs in treatment-resistant
      people, multiple-session family interventions, psychoeducational interventions,
      and second-generation antipsychotic drugs in treatment-resistant people.

PMID- 23870701
TI  - Joubert syndrome: congenital cerebellar ataxia with the molar tooth.
AB  - Joubert syndrome is a congenital cerebellar ataxia with autosomal recessive or X
      linked inheritance, the diagnostic hallmark of which is a unique cerebellar and
      brainstem malformation recognisable on brain imaging-the so-called molar tooth
      sign. Neurological signs are present from the neonatal period and include
      hypotonia progressing to ataxia, global developmental delay, ocular motor
      apraxia, and breathing dysregulation. These signs are variably associated with
      multiorgan involvement, mainly of the retina, kidneys, skeleton, and liver. 21
      causative genes have been identified so far, all of which encode for proteins of
      the primary cilium or its apparatus. The primary cilium is a subcellular
      organelle that has key roles in development and in many cellular functions,
      making Joubert syndrome part of the expanding family of ciliopathies. Notable
      clinical and genetic overlap exists between distinct ciliopathies, which can co
      occur even within families. Such variability is probably explained by an
      oligogenic model of inheritance, in which the interplay of mutations, rare
      variants, and polymorphisms at distinct loci modulate the expressivity of the
      ciliary phenotype. 

PMID- 23870706
TI  - Clinical and economical consequences of the combination of metformin with
      dipeptidyl peptidase inhibitors in type 2 diabetes patients.
AB  - BACKGROUNDS AND OBJECTIVE: There are different second line glucose lowering drugs
      whose efficacy, safety and economic profile have not been established in our
      setting. We have analyzed the clinical (diabetic treatment adherence, metabolic
      control, hypoglycemia and macrovascular complications) and economic (resource use
      and costs) consequences of the combination of metformin with dipeptidyl peptidase
      inhibitors (DPPIV) in patients with type 2 diabetes. PATIENTS AND METHODS: We
      conducted a multicenter, observational and retrospective study. Patients >=30
      years treated with metformin who initiated a second antidiabetic treatment during
      2008-2009 were enrolled in the study. Two groups of patients were established: a)
      metformin with DPPIV and metformin with other diabetic drugs. The main
      measurements were comorbidity, compliance/persistence, metabolic control
      (glycosylated hemoglobin <7%), complications (hypoglycemia, macrovascular) and
      total costs. Patients were followed-up for 2 years. RESULTS: A total of 2,067
      patients were enrolled (mean age: 66.6 years, 53.1% male). Of these, 519 patients
      (25.1%) were analyzed in the metformin+DPPIV group and 1,548 patients (74.9%) in
      the group metformin+other antidiabetic drug. The DPPIV group patients showed
      better compliance (70.3 vs. 59.6%), persistence (63.4 vs. 51.0%) and metabolic
      control (64.3 vs. 59.6%), respectively (P<.001) compared to the other group. They
      also showed a lower proportion of hypoglycemia (13.9 vs. 44.3%), cardiovascular
      events (3.7 vs. 7.6%) and total costs (2,347 vs. ? 2,682), P<.05. CONCLUSIONS:
      Despite the limitations of the study, patients treated with metformin associated
      to DPPIV were more likely to show increased adherence, metabolic control and
      lower rates of hypoglycemia than those treated with metformin associated to other
      antidiabetics.

PMID- 23870707
TI  - Abundance of pathogens in the gut and litter of broiler chickens as affected by
      bacitracin and litter management.
AB  - Clostridium perfringens, Salmonella spp. and Campylobacter spp. are food-borne
      enteric pathogens that are commonly associated with poultry. The objective of
      this study was to investigate the effects of supplemental bacitracin and litter
      management (fresh vs. reused) on the abundance of these pathogens in commercial
      broiler chickens. Specific quantitative PCR (qPCR) assays were used to quantify
      C. perfringens, virulent C. perfringens that carried the genes encoding alpha
      toxin (cpa) and NetB-toxin (netB), Salmonella, and Campylobacter in samples of
      ileal mucosa, cecal content, and litter. Campylobacter was not detected in any of
      the samples collected. The abundance of Salmonella was not affected by either
      bacitracin or litter condition. Generic C. perfringens was detected in the ileal
      mucosa at very low level at 10 days of age but was much higher at 35 days.
      Chickens reared on reused litter tended to have a lower abundance of generic C.
      perfringens compared with those reared on fresh litter. In the ileal mucosa, no
      cpa or netB was detected at day 10 but was detected at day 35 in the chickens
      that were not fed supplemental bacitracin. Chicks fed supplemental bacitracin had
      reduced abundance of generic C. perfringens as well as the cpa and netB genes in
      the ileal mucosa, cecal content, and litters. A strong positive correlation was
      found between the abundance of all three measurements of C. perfringens. The
      abundance of Salmonella spp. and C. perfringens was also shown to be correlated.
      This is the first study that has examined the effect of dietary bacitracin and
      litter conditions on the prevalence of these three common enteric pathogens.
      Unless contaminated from previous flocks, reused litter may not necessarily
      contain significantly greater abundances of C. perfringens or Salmonella. 

PMID- 23870710
TI  - Antibacterial activities and antioxidant capacity of Aloe vera.
AB  - BACKGROUND: The aim of this study was to identify, quantify, and compare the
      phytochemical contents, antioxidant capacities, and antibacterial activities of
      Aloe vera lyophilized leaf gel (LGE) and 95% ethanol leaf gel extracts (ELGE)
      using GC-MS and spectrophotometric methods. RESULTS: Analytically, 95% ethanol is
      less effective than ethyl acetate/diethyl ether or hexane (in the case of fatty
      acids) extractions in separating phytochemicals for characterization purposes.
      However, although fewer compounds are extracted in the ELGE, they are
      approximately 345 times more concentrated as compared to the LGE, hence
      justifying ELGE use in biological efficacy studies in vivo. Individual
      phytochemicals identified included various phenolic acids/polyphenols,
      phytosterols, fatty acids, indoles, alkanes, pyrimidines, alkaloids, organic
      acids, aldehydes, dicarboxylic acids, ketones, and alcohols. Due to the presence
      of the antioxidant polyphenols, indoles, and alkaloids, the A. vera leaf gel
      shows antioxidant capacity as confirmed by ORAC and FRAP analyses. Both
      analytical methods used show the non-flavonoid polyphenols to contribute to the
      majority of the total polyphenol content. Three different solvents such as
      aqueous, ethanol, and acetone were used to extract the bioactive compounds from
      the leaves of A. vera to screen the antibacterial activity selected human
      clinical pathogens by agar diffusion method. The maximum antibacterial activities
      were observed in acetone extracts (12 +/- 0.45, 20 +/- 0.35, 20 +/- 0.57, and 15
      +/- 0.38 nm) other than aqueous and ethanol extracts. CONCLUSION: Due to its
      phytochemical composition, A. vera leaf gel may show promise in alleviating
      symptoms associated with/or prevention of cardiovascular diseases, cancer,
      neurodegeneration, and diabetes.

PMID- 23870708
TI  - Modest additive effects of integrated vector control measures on malaria
      prevalence and transmission in western Kenya.
AB  - BACKGROUND: The effect of integrating vector larval intervention on malaria
      transmission is unknown when insecticide-treated bed-net (ITN) coverage is very
      high, and the optimal indicator for intervention evaluation needs to be
      determined when transmission is low. METHODS: A post hoc assignment of
      intervention-control cluster design was used to assess the added effect of both
      indoor residual spraying (IRS) and Bacillus-based larvicides (Bti) in addition to
      ITN in the western Kenyan highlands in 2010 and 2011. Cross-sectional, mass
      parasite screenings, adult vector populations, and cohort of active case
      surveillance (ACS) were conducted before and after the intervention in three
      study sites with two- to three-paired intervention-control clusters at each site
      each year. The effect of larviciding, IRS, ITNs and other determinants of malaria
      risk was assessed by means of mixed estimating methods. RESULTS: Average ITN
      coverage increased from 41% in 2010 to 92% in 2011 in the study sites. IRS
      intervention had significant added impact on reducing vector density in 2010 but
      the impact was modest in 2011. The effect of IRS on reducing parasite prevalence
      was significant in 2011 but was seasonal specific in 2010. ITN was significantly
      associated with parasite densities in 2010 but IRS application was significantly
      correlated with reduced gametocyte density in 2011. IRS application reduced about
      half of the clinical malaria cases in 2010 and about one-third in 2011 compare to
      non-intervention areas. CONCLUSION: Compared with a similar study conducted in
      2005, the efficacy of the current integrated vector control with ITN, IRS, and
      Bti reduced three- to five-fold despite high ITN coverage, reflecting a modest
      added impact on malaria transmission. Additional strategies need to be developed
      to further reduce malaria transmission.

PMID- 23870712
TI  - Do multimedia based information services increase knowledge and satisfaction in
      head and neck cancer patients?
AB  - OBJECTIVES: To investigate the impact of a Multimode Comprehensive Tailored
      Information Package (MCTIP) on Head and Neck (H&N) cancer patients' knowledge and
      satisfaction. METHODS: A non-randomized controlled trial was conducted at two
      participating hospitals. One hospital delivered the MCTIP and the second hospital
      provided normal care. The study was approved by local ethical committees.
      Patients with Stage III and IV cancer in the H&N region were recruited between
      their diagnosis and treatment. All participants were evaluated at baseline, 3 and
      6months later using the Satisfaction with Cancer Information Profile (SCIP) and a
      Cancer Knowledge questionnaire. Data were analyzed using descriptive statistics,
      T tests, chi square tests and finally linear mixed model analyses to test the
      potential impact of the intervention. RESULTS: A total of 103 participants
      participated in this study and complete data at all time points were collected
      for 96. The Test group reported higher levels of Cancer Knowledge and
      Satisfaction at all time points (p<0.001 with all comparisons) compared to the
      Control group. CONCLUSION: Our study demonstrated an association between
      receiving the multimedia based tailored information and higher levels of
      satisfaction and cancer knowledge compared to those who receive information in ad
      hoc manner. IMPLICATIONS: Exploring patients' informational needs is necessary
      before planning information services to them.

PMID- 23870713
TI  - Attenuation of neuropathic pain by sodium butyrate in an experimental model of
      chronic constriction injury in rats.
AB  - BACKGROUND/PURPOSE: The present study was designed to investigate the potential
      of sodium butyrate, a histone deacetylase (HDAC) inhibitor, in chronic
      constriction injury (CCI)-induced neuropathic pain in rats. METHODS: Neuropathic
      pain was induced by placing four loose ligatures around the sciatic nerve.
      Acetone drop, Von frey hair, pin prick and hot plate tests were performed to
      assess cold allodynia, mechanical allodynia, and mechanical and heat
      hyperalgesia, respectively. The level of tumor necrosis factor (TNF)-alpha was
      measured in the sciatic nerve as an inflammatory marker. RESULTS: CCI was
      associated with the development of cold allodynia, mechanical allodynia, and
      mechanical and heat hyperalgesia, along with an increase in TNF-alpha level.
      Administration of sodium butyrate (200 and 400 mg/kg, oral) for 14 days in CCI
      subjected rats significantly attenuated behavior related to injury-induced pain
      and the increase in TNF-alpha level. CONCLUSION: It may be concluded that the
      anti-inflammatory actions mediated by sodium butyrate are responsible for its
      beneficial effects in neuropathic pain in rats.

PMID- 23870714
TI  - Frontal soft tissue analysis using a 3 dimensional camera following two-jaw
      rotational orthognathic surgery in skeletal class III patients.
AB  - Although two dimensional cephalometry is the standard method for analyzing the
      results of orthognathic surgery, it has potential limits in frontal soft tissue
      analysis. We have utilized a 3 dimensional camera to examine changes in soft
      tissue landmarks in patients with skeletal class III dentofacial deformity who
      underwent two-jaw rotational setback surgery. We assessed 25 consecutive Asian
      patients (mean age, 22 years; range, 17-32 years) with skeletal class III
      dentofacial deformities who underwent two-jaw rotational surgery without
      maxillary advancement. Using a 3D camera, we analyzed changes in facial
      proportions, including vertical and horizontal dimensions, facial surface areas,
      nose profile, lip contour, and soft tissue cheek convexity, as well as landmarks
      related to facial symmetry. The average mandibular setback was 10.7 mm (range: 5
      17 mm). The average SNA changed from 77.4 degrees  to 77.8 degrees , the average
      SNB from 89.2 degrees  to 81.1 degrees , and the average occlusal plane from 8.7
      degrees  to 11.4 degrees . The mid third vertical dimension changed from 58.8 mm
      to 57.8 mm (p = 0.059), and the lower third vertical dimension changed from 70.4
      mm to 68.2 mm (p = 0.0006). The average bigonial width decreased from 113.5 mm to
      109.2 mm (p = 0.0028), the alar width increased from 34.7 mm to 36.1 mm (p-value
      = 0.0002), and lip length was unchanged. Mean mid and lower facial surface areas
      decreased significantly, from 171.8 cm(2) to 166.2 cm(2) (p = 0.026) and from
      71.23 cm(2) to 61.9 cm(2) (p < 0.0001), respectively. Cheek convexity increased
      significantly, from 171.8 degrees  to 155.9 degrees  (p = 0.0007). The 3D camera
      was effective in frontal soft tissue analysis for orthognathic surgery, and
      enabled quantitative analysis of changes in frontal soft tissue landmarks and
      facial proportions that were not possible with conventional 2D cephalometric
      analysis.

PMID- 23870715
TI  - High levels of soluble CD40 ligand and matrix metalloproteinase-9 in serum are
      associated with favorable clinical evolution in human visceral leishmaniasis.
AB  - BACKGROUND: Soluble CD40 ligand (sCD40L) and matrix metalloproteinase 9 (MMP-9)
      are inflammation markers and have been poorly described in infectious disease. In
      this prospective study, we describe the sera kinetics of these two molecules in
      the course of treatment follow up in human visceral leishmaniasis (VL). METHODS:
      Sera from VL patients were collected before and during follow up of regular
      Antimony treatment. sCD40L and MMP-9 were measured by Luminex assay. Paired
      analysis by Wilcoxon signed test was used for comparison of values of the same
      subjects before and after initiation of treatment. Correlations between clinical
      data and parasite load with the serum levels of sCD40L and MMP-9 were performed
      by Spearman test. Tests were considered statistically significant if the
      probability of a type I error was less than 5% (p-value < 0.05). RESULTS: While
      sCD40L and MMP-9 were not observed in sera from non endemic controls which are at
      low risk of Leishmania chagasi infection, elevated levels were observed in sera
      from VL patients, and an increase in sCD40L and MMP-9 levels were detectable
      during the follow-up of VL patients undergoing antimony treatment. sCD40L levels
      were also high in individuals living in endemic settings at high risk of
      infection (endemic controls). Additionally, negative correlations were found
      between spleen sizes and MMP-9 before treatment and sCD40L at day 15 of
      treatment. Negative correlations were also found between parasite load with both
      sCD40L and MMP-9. CONCLUSION: Serum sCD40L and MMP-9 are identified as new and
      simple biomarkers in two situations: (i) monitoring the success of therapy and
      (ii) predicting favorable clinical outcome of human VL.

PMID- 23870716
TI  - Common carotid artery occlusion treatment: revealing a gap in the current
      guidelines.
AB  - OBJECTIVE: To review the literature on the management of common carotid artery
      occlusion (CCAO). METHODS: A review of English-language medical literature from
      1965 to 2012 was conducted using the PubMed and EMBASE databases to find all
      studies involving management of CCAO. The search identified 21 articles
      encompassing 146 patients/arteries (73.2% men; mean age 65 +/- 6.9 years).
      RESULTS: The majority of the patients (93.8%) were symptomatic. Most of the
      patients (61.5%) had ipsilateral internal carotid artery (ICA) and external
      carotid artery (ECA) patent, while an occluded ICA and a patent ECA were found in
      26.6% of the patients. Eighty per cent of the patients treated underwent a
      surgical bypass procedure, with the subclavian artery as the most common inflow
      vessel (64.1%). During the first 30 days of the procedure two strokes (1.5%) were
      reported. During a follow-up period spanning an average of 25.6 +/- 11.2 months
      nine patients (6.6%) experienced a clinical cerebrovascular event. Seven
      restenoses (5.1%) and two reocclusions (1.5%) also occurred-eight after open
      surgical and one after endovascular repair. CONCLUSION: The necessity to
      intervene to a CCAO remains controversial. This review shows that open surgical
      management of symptomatic CCA occlusive disease is a safe, durable, and effective
      therapeutic strategy with low perioperative cerebrovascular morbidity.

PMID- 23870717
TI  - Protocol for the evaluation of a pay for performance programme in Pwani region in
      Tanzania: a controlled before and after study.
AB  - BACKGROUND: The use of supply-side incentives to increase health service
      utilisation and enhance service quality is gaining momentum in many low- and
      middle-income countries. However, there is a paucity of evidence on the impact of
      such schemes, their cost-effectiveness, and the process of implementation and
      potential unintended consequences in these settings. A pay for performance (P4P)
      programme was introduced in Pwani region of Tanzania in 2011. METHODS/DESIGN: An
      evaluation of the programme will be carried out to inform a potential national
      rollout. A controlled before and after study will examine the effect of the P4P
      programme on quality, coverage, and cost of targeted maternal and newborn
      healthcare services and selected non-targeted services at facilities in Tanzania.
      Data will be collected from a survey of 75 facilities, 750 patients exiting
      consultations, over 75 health workers, and 1,500 households of women who
      delivered in the previous year, in all seven intervention districts. Data will be
      collected from the same number of respondents in four control districts. A
      process evaluation will examine: whether the P4P programme was implemented as
      planned; stakeholder response to the programme and its acceptability; and
      implementation bottlenecks and facilitating factors. Three rounds of process data
      collection will be conducted including a review of available P4P documents,
      individual interviews and focus group discussions with key informants working at
      facility and district level in five of the intervention districts, and at the
      regional and national levels. An economic evaluation will measure the cost
      effectiveness of P4P relative to current practice from a societal perspective.
      DISCUSSION: This evaluation will contribute robust evidence on the impact and
      cost-effectiveness of P4P in a low income setting, as well as generate a better
      understanding of the feasibility of integrating complex intervention packages
      like P4P within health systems in resource poor settings.

PMID- 23870718
TI  - Reviewing psychological treatments for adult depression.

PMID- 23870719
TI  - A meta-analysis of cognitive-behavioural therapy for adult depression, alone and
      in comparison with other treatments.
AB  - OBJECTIVE: No recent meta-analysis has examined the effects of cognitive
      behavioural therapy (CBT) for adult depression. We decided to conduct such an
      updated meta-analysis. METHODS: Studies were identified through systematic
      searches in bibliographical databases (PubMed, PsycINFO, Embase, and the Cochrane
      library). We included studies examining the effects of CBT, compared with control
      groups, other psychotherapies, and pharmacotherapy. RESULTS: A total of 115
      studies met inclusion criteria. The mean effect size (ES) of 94 comparisons from
      75 studies of CBT and control groups was Hedges g = 0.71 (95% CI 0.62 to 0.79),
      which corresponds with a number needed to treat of 2.6. However, this may be an
      overestimation of the true ES as we found strong indications for publication bias
      (ES after adjustment for bias was g = 0.53), and because the ES of higher-quality
      studies was significantly lower (g = 0.53) than for lower-quality studies (g =
      0.90). The difference between high- and low-quality studies remained significant
      after adjustment for other study characteristics in a multivariate meta
      regression analysis. We did not find any indication that CBT was more or less
      effective than other psychotherapies or pharmacotherapy. Combined treatment was
      significantly more effective than pharmacotherapy alone (g = 0.49). CONCLUSIONS:
      There is no doubt that CBT is an effective treatment for adult depression,
      although the effects may have been overestimated until now. CBT is also the most
      studied psychotherapy for depression, and thus has the greatest weight of
      evidence. However, other treatments approach its overall efficacy.

PMID- 23870720
TI  - Psychotherapy, antidepressants, and their combination for chronic major
      depressive disorder: a systematic review.
AB  - OBJECTIVE: Recommendations for treatment of chronic major depressive disorder
      (cMDD) are mostly based on clinical experiences and on the literature on
      treatment-resistant depression (TRD) but not on a systematic review of the
      literature. METHOD: We conducted a systematic review of 10 randomized controlled
      trials (RCTs), with 17 comparisons between antidepressants (ADs), psychotherapy,
      or the combination of both interventions. RESULTS: The best evidence is for the
      combination of psychotherapy and ADs, and especially for the combination of the
      cognitive behavourial analysis system of psychotherapy and ADs. Evidence is very
      weak for both ADs alone and psychotherapy alone. Assessment of TRD was mostly
      absent in the studies. CONCLUSION: The best treatment for cMDD is a combination
      of psychotherapy and ADs. However, there is a lack of well-performed RCTs in both
      ADs and psychotherapy and their combination for cMDD. Therefore, the conclusions
      are preliminary.

PMID- 23870721
TI  - Comorbid anxiety disorders in Canadians with bipolar disorder: clinical
      characteristics and service use.
AB  - OBJECTIVE: To examine the impact of anxiety disorders comorbid to bipolar
      disorder (BD) in a large, nationally representative sample, to describe the
      sociodemographic and clinical profiles of Canadians living with BD and with or
      without comorbid anxiety disorders, to identify the characteristics uniquely
      associated with comorbid anxiety, and to examine treatment patterns. METHOD: We
      analyzed data from the Canadian Community Health Survey: Mental Health and Well
      Being, conducted among 38 492 Canadians. People meeting the criteria for BD (n =
      808) were compared based on the presence or absence of an assessed anxiety
      disorder (that is, social phobia, panic disorder, and agoraphobia). RESULTS:
      People with BD and a comorbid anxiety disorder fare worse in terms of BD
      relapses, suicidality, and sleep disturbance, and are more likely to be taking
      psychiatric medication. They have more impairment in their work and social
      functioning and rate their health and life satisfaction lower. Despite the
      greater severity, they are not receiving additional psychological treatment, they
      feel they are not receiving the treatment they need, and they report more
      barriers to treatment. CONCLUSIONS: This study confirms the critical impact of
      comorbid anxiety on the course of BD in a large, nationally representative sample
      and reveals that the psychological treatment needs of this population are not
      being met. Clinical and research implications are discussed.

PMID- 23870723
TI  - Psychiatric symptoms associated with brief detention of adult asylum seekers in
      Canada.
AB  - OBJECTIVES: To examine the association between brief detention and psychiatric
      symptom levels among adult asylum seekers. METHOD: The Harvard Trauma
      Questionnaire and the Hopkins Symptoms Checklist-25 were used to assess
      psychiatric symptoms and premigration trauma exposure in 122 detained and 66
      nondetained adult asylum seekers in Montreal and Toronto. RESULTS: After a mean
      detention of 31 days, the proportion of asylum seekers scoring above clinical
      cutpoints was significantly higher in the detained than the nondetained group for
      posttraumatic stress (chi2 = 4.117, df = 1, P = 0.04), depression (chi2 = 13.813,
      df = 1, P < 0.001), and anxiety (chi2 = 4.567, df = 1, P = 0.03) symptoms.
      Hierarchical multiple regression models showed that posttraumatic stress,
      depression, and anxiety symptom levels were significantly higher among detained
      asylum seekers than among the nondetained comparison group, taking into account
      previous trauma and demographics. Incremental F was significant for the addition
      of detention status for all 3 models, indicating that detention contributed to
      increased symptom levels. CONCLUSIONS: For asylum seekers, even brief detention
      is associated with increased psychiatric symptoms. Governments should consider
      the many viable alternatives to incarceration of asylum seekers, such as
      temporary placement in a supervised residential facility, to minimize the risks
      of psychological harm to this vulnerable population.

PMID- 23870722
TI  - Omega-3 fatty acid supplementation in adolescents with borderline personality
      disorder and ultra-high risk criteria for psychosis: a post hoc subgroup analysis
      of a double-blind, randomized controlled trial.
AB  - OBJECTIVE: To investigate whether long-chain omega-3 (n-3) polyunsaturated fatty
      acids (PUFAs) improve functioning and psychiatric symptoms in young people with
      borderline personality disorder (BPD) who also meet ultra-high risk criteria for
      psychosis. METHODS: We conducted a post hoc subgroup analysis of a double-blind,
      randomized controlled trial. Fifteen adolescents with BPD (mean age 16.2 years,
      [SD 2.1]) were randomized to either 1.2 g/day n-3 PUFAs or placebo. The
      intervention period was 12 weeks. Study measures included the Positive and
      Negative Syndrome Scale, the Montgomery-Asberg Depression Rating Scale, and the
      Global Assessment of Functioning. Side effects were documented with the Udvalg
      for Kliniske Undersogelser. Fatty acids in erythrocytes were analyzed using
      capillary gas chromatography. RESULTS: At baseline, erythrocyte n-3 PUFA levels
      correlated positively with psychosocial functioning and negatively with
      psychopathology. By the end of the intervention, n-3 PUFAs significantly improved
      functioning and reduced psychiatric symptoms, compared with placebo. Side effects
      did not differ between the treatment groups. CONCLUSIONS: Long-chain n-3 PUFAs
      should be further explored as a viable treatment strategy with minimal associated
      risk in young people with BPD. ( CLINICAL TRIAL REGISTRATION NUMBER:
      NCT00396643).

PMID- 23870724
TI  - Symptoms of posttraumatic stress disorder and depression in relation to alcohol
      use and alcohol-related problems among Canadian forces veterans.
AB  - OBJECTIVE: Alcohol misuse is common among military veterans affected by
      posttraumatic stress disorder (PTSD) and depression; however, research to date
      has provided mixed evidence concerning differential associations among PTSD and
      depressive symptoms in relation to alcohol misuse. Further, most available
      studies have examined primarily male samples or have dichotomously grouped
      participants as either having or not having an alcohol use disorder. Our study
      sought to explore relations among 2 aspects of alcohol misuse (that is, alcohol
      related problems, and quantity or frequency of alcohol use) and symptoms of PTSD
      and depression in independent samples of female and male military veterans.
      METHOD: Canadian military veterans (1271 men and 72 women) completed a battery of
      self-report questionnaires as part of a broader health status assessment
      conducted by Veterans Affairs Canada. RESULTS: Linear regression analyses
      suggested depressive symptoms accounted for unique variance in reported alcohol
      related problems and quantity or frequency of alcohol use among male veterans.
      Additionally, PTSD hyperarousal symptoms accounted for unique variance in
      reported alcohol-related problems. In contrast, among female veterans neither
      PTSD nor depressive symptoms were found to account for significant variance in
      measures of alcohol-related problems or quantity or frequency of alcohol use.
      CONCLUSIONS: Findings suggest differing mechanisms are involved in influencing
      alcohol misuse among male and female veterans. Accordingly, female veterans may
      benefit from specialized assessment and intervention approaches to prevent and
      treat alcohol-related disorders, rather than applying the same strategies
      commonly used with male veterans. Comprehensive results, implications, and
      directions for future research are discussed.

PMID- 23870725
TI  - Trends in psychotropic use in Saskatchewan from 1983 to 2007.
AB  - OBJECTIVE: There has been little research reported on trends in the use of a full
      spectrum of psychotropics in a general population. We provide an overview of
      trends in psychotropic use over a 24-year period for Saskatchewan. METHODS: Data
      were drawn from the Saskatchewan Ministry of Health administrative data files. It
      covers antidepressants (ADs), antipsychotics, mood stabilizers, anxiolytics,
      stimulants, and cholinesterase inhibitors in outpatient settings. We analyzed
      data from 9 triennial years from 1983 to 2007. Descriptive statistics were used.
      RESULTS: Among the Saskatchewan population in our study, 8.38% were prescribed at
      least 1 psychotropic in 1983. The prevalence decreased to 7.44% in 1989, then
      gradually increased to 12.90% in 2007. We found a continuous increase in the
      number of psychotropic prescriptions for both males and females. The trend became
      more marked during the 1990s. Females used more psychotropics. Family physicians
      were the major prescribers, and their prescriptions dramatically increased over
      the period. There was an increase in the prescribing of all psychotropics except
      for anxiolytics. AD prescriptions dramatically increased, especially from 1995
      onward. The proportion of patients with 8 to 11 and 12 or more prescriptions per
      year also gradually increased, whereas the proportion of patients with less than
      3 prescriptions per year decreased. CONCLUSIONS: AD prescriptions are the major
      reason for the increasing trend of psychotropic use. Given the major role of
      family physicians in the use of psychotropics, the need for appropriate training
      and continuing education is reinforced.

PMID- 23870726
TI  - Sense of belonging and suicide: a systematic review.
AB  - OBJECTIVE: To systematically review the research on the association between sense
      of belonging and suicide. METHOD: We systematically reviewed electronic databases
      for studies that included assessments of suicidality and belonging. RESULTS: We
      found 16 studies that met our eligibility criteria. They all found an association
      between belonging and suicidality but nearly all of the studies were in
      nonclinical populations, and the association was weak and could be taken into
      account by confounding factors. CONCLUSIONS: Low sense of belonging has a weak
      association with suicidality. However, current concepts make it hard to
      distinguish from loneliness or other measures of social support. An alternative
      view of belongingness, as a sense of connectedness to things other than people
      and in the past as well as the present, may generate alternative ideas about
      useful clinical interventions that may be especially relevant to indigenous
      populations.

PMID- 23870727
TI  - Granulocytapheresis in steroid-dependent and steroid-resistant patients with
      inflammatory bowel disease: a prospective observational study.
AB  - BACKGROUND: Despite the mounting importance of granulocytapheresis (GCAP) for
      inflammatory bowel disease (IBD) treatment, its effectiveness in steroid
      dependent (SD) and steroid-resistant (SR) patients has not been clearly
      evaluated. This prospective observational study describes the use of GCAP in SD
      and SR patients with either Ulcerative Colitis (UC) or Crohn's Disease (CD).
      METHODS: 118 patients, 83 affected by UC (55 SD and 28 SR) and 35 by CD (22 SD
      and 13 SR), were treated with GCAP, using AdacolumnTM, for 5 consecutive weeks, 1
      session/week. All patients were followed for 12 months after the end of GCAP.
      Clinical remission was defined as Clinical Activity Index (CAI) <=6 for UC
      patients and Crohn's Disease Activity Index (CDAI) <150 for CD patients. RESULTS:
      All patients completed the study; no major complications were reported. At the
      end of GCAP 71% of UC and 63% of CD patients showed clinical remission. At 6
      months the remission was maintained by 66% and 54% of UC and CD patients
      respectively, while at 12 months the percentages were 48% and 43%, respectively.
      No differences between SD and SR subgroups were reported at any timepoint. CAI
      and CDAI values significantly dropped after GCAP treatment and at 6 and 12
      months' follow-up (p<0.05 vs baseline for both timepoints). No differences were
      measured in CAI and CDAI between SD and SR patients. CONCLUSION: GCAP therapy is
      safe and effective in inducing and maintaining clinical remission both in SD and
      in SR patients affected by either UC or CD.

PMID- 23870728
TI  - European consensus on the histopathology of inflammatory bowel disease.
AB  - The histologic examination of endoscopic biopsies or resection specimens remains
      a key step in the work-up of affected inflammatory bowel disease (IBD) patients
      and can be used for diagnosis and differential diagnosis, particularly in the
      differentiation of UC from CD and other non-IBD related colitides. The
      introduction of new treatment strategies in inflammatory bowel disease (IBD)
      interfering with the patients' immune system may result in mucosal healing,
      making the pathologists aware of the impact of treatment upon diagnostic
      features. The European Crohn's and Colitis Organisation (ECCO) and the European
      Society of Pathology (ESP) jointly elaborated a consensus to establish standards
      for histopathology diagnosis in IBD. The consensus endeavors to address: (i)
      procedures required for a proper diagnosis, (ii) features which can be used for
      the analysis of endoscopic biopsies, (iii) features which can be used for the
      analysis of surgical samples, (iv) criteria for diagnosis and differential
      diagnosis, and (v) special situations including those inherent to therapy.
      Questions that were addressed include: how many features should be present for a
      firm diagnosis? What is the role of histology in patient management, including
      search for dysplasia? Which features if any, can be used for assessment of
      disease activity? The statements and general recommendations of this consensus
      are based on the highest level of evidence available, but significant gaps remain
      in certain areas. 

PMID- 23870729
TI  - Association of amoxicillin use and molar incisor hypomineralization in piglets:
      visual and mineral density evaluation.
AB  - AIM: The aim of the present study was to determine the prevalence of MIH both
      visually and quantitatively, and describes the range of mineral densities of
      enamel specimens from three groups of piglets where two groups were given
      different doses of amoxicillin in infancy. METHODS: In this blind randomized
      clinical study, 20 piglets were randomly divided into three groups. Group A
      received a standard dose (50mg/kg/day) and Group B received a high dose
      (90mg/kg/day) of amoxicillin in selected days of the month (20 working days) they
      were born. Group K did not receive any medication and served as control. Thirteen
      right mandibular permanent first molars (PFMs) were randomly collected from 3
      groups of piglets at age 10 months for evaluation under X-ray micro-tomography.
      Tomographic data were obtained using a Skyscan 1174 compact micro-CT in the
      Department of Anatomy. RESULTS: Prevalence of MIH was 0% in all groups. MD values
      were quantified after enamel grey level (0-255) measurements on horizontal cross
      sectional slices. After MD measurements, the effects of amoxicillin use on MIH
      are presented. CONCLUSIONS: While MIH is a multifactorial disturbance, the
      present study attempted to highlight the clinical findings of a possible
      relationship between amoxicillin use and MIH with the aid of X-ray micro
      tomography.

PMID- 23870730
TI  - Caffeine increases the expression of cystatin SN in human submandibular acinar
      like HSG cells.
AB  - OBJECTIVE: The study aimed at evaluating in vitro the effect of caffeine on
      expression of cystatin SN, a potential marker of sensitivity to bitterness in
      humans. METHODS: Differentiation of human submandibular gland (HSG) cells was
      induced by culturing cells on Matrigel. Caffeine cytotoxicity was assessed over 3
      days by the Resazurin test. Finally, effects of 5, 50 and 100MUM caffeine
      exposure on cystatin SN expression were explored over 3 days by ELISA. RESULTS:
      At concentrations relevant to human adult plasma levels (5, 50 and 100MUM),
      caffeine did not affect cell viability whether cells were differentiated or not.
      Cystatin SN levels were overall higher in differentiated cells and increased with
      time in both conditions. There was a significant (p<0.001) effect of caffeine on
      cystatin SN expression specifically in differentiated cells. CONCLUSIONS: The HSG
      cell line proved to be a relevant tool to study in vitro the effect of caffeine
      at concentrations consistent with dietary intake in human subjects. The results
      suggest that salivary cystatin SN abundance may depend on caffeine intake, with
      possible consequences on taste sensitivity.

PMID- 23870731
TI  - Concurrence of villous adenoma and non-muscle invasive bladder cancer arising in
      the bladder: a case report and review of the literature.
AB  - BACKGROUND: Villous adenoma arising in the urinary tract is rare tumor. Most
      cases have been identified as benign neoplasm in the colon. Villous adenoma of
      the gastrointestinal tract is thought arise from premalignant polyps. Here, we
      report a case of concurrence of villous adenoma and non-muscle invasive bladder
      cancer. CASE PRESENTATION: An 85-year-old woman presented at our office because
      of gross hematuria. Cystoscopic examination detected two papillary tumors in the
      bladder. Each tumor was resected and diagnosed, respectively. Histopathology
      confirmed that the resected one tumor was a villous adenoma, and the other was
      urothelial carcinoma (T1, high grade). Immunostaining for cytokeratin (CK) 7,
      CK20 and Ki-67 confirmed that CK7: (-), CK20: (+) and Ki-67: (<=30%) in villous
      adenoma while CK7: (+), CK20: (+), and Ki-67: (70%) in urothelial carcinoma.
      Three months later from TUR, urothelial carcinoma recurred in the trigone. She
      received adjuvant intravesical immunotherapy with BCG post TUR for the recurrence
      site. CONCLUSION: There were no specific findings on ultrasonography, CT, MRI or
      cystoscopic examination morphologically. Therefore, pre-pathological villous
      adenoma of the bladder is extremely difficult to diagnose. There are some case
      reports of solitary villous adenoma in the bladder or with coexisting adeno
      carcinoma. However, to the best of our knowledge, this is only the second report
      of villous adenoma in the bladder of coexisting urothelial carcinoma that has
      been published in the literature. Premalignant villous adenoma of the bladder is
      extremely rare and difficult to diagnose without histologic examination. Any
      suspicious lesion of the bladder should be biopsied and/or resected to confirm
      histology.

PMID- 23870732
TI  - Cryptosporidium hominis subtypes and Enterocytozoon bieneusi genotypes in HIV
      infected persons in Ibadan, Nigeria.
AB  - Cryptosporidium and Enterocytozoon are common opportunistic pathogens in HIV+
      patients in developing countries, especially those do not have access to
      antiretroviral therapy. To determine the distribution of genotypes/subtypes of
      Cryptosporidium and Enterocytozoon bieneusi, faecal specimens were collected from
      132 HIV+ persons attending a tertiary hospital in Ibadan, Nigeria. By polymerase
      chain reaction, eight and ten patients were identified as positive for
      Cryptosporidium spp. and E. bieneusi, respectively. Seven of the Cryptosporidium
      specimens were identified as C. hominis, while the remaining one as the new
      species C. viatorum recently identified in the United Kingdom. DNA sequencing of
      the 60-kDa glycoprotein gene showed that the C. hominis belonged to three common
      subtype families: Ia (in three patients), Ib (in one patient) and Ie (in one
      patient). In contrast, DNA sequencing of the E. bieneusi internal transcribed
      spacer products showed the occurrence of genotypes associated with both humans
      (Peru 8 in one patient, Nig2 in two patients and a new genotype in one patient)
      and animals (D in one patient and Type IV in five patients). Low CD4+ cell count
      was identified as a risk factor for both cryptosporidiosis and microsporidiosis.

PMID- 23870733
TI  - Using Medicare data to assess nurse practitioner-provided care.
AB  - BACKGROUND: To mitigate shortages of primary care physicians and ensure access to
      health care services for a growing number of Medicare beneficiaries, some policy
      makers have recommended expanding the supply and roles of nurse practitioners
      (NPs). Little is known about the number of NPs billing Medicare or their practice
      patterns. PURPOSE: This study examines the geographic distribution and county
      characteristics of NPs billing Medicare, compares the types and quantities of
      primary care services provided to Medicare beneficiaries by NPs and primary care
      physicians, and analyzes the characteristics of beneficiaries receiving primary
      care from each type of clinician. METHODS: We performed a cross-sectional
      analysis of 2008 Medicare administrative data from 959,848 aged and/or disabled
      beneficiaries continuously enrolled in fee-for-service Medicare during the study
      period. Outcome measures included geographic distribution of NPs measured by the
      rate of NPs per 1,000 Medicare beneficiaries by state, average utilization, and
      patient characteristics. DISCUSSION: States with the highest rate of NPs billing
      were rural. Over 80% of the payments received by both NPs and primary care
      physicians were for evaluation and management services. Beneficiaries assigned to
      an NP were more likely to be female, to be dually eligible for Medicare and
      Medicaid, and to have qualified for Medicare because of a disability. NPs with
      assigned beneficiaries were significantly more likely than similar primary care
      physicians to practice in federally designated primary care shortage areas.
      CONCLUSIONS: Approximately 45,000 NPs were providing services to beneficiaries
      and billing under their own provider numbers in 2008. Aspects of NP practice
      patterns were different from primary care physicians, and NPs appeared more
      likely to provide services to disadvantaged Medicare beneficiaries.

PMID- 23870734
TI  - Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice
      at 3 Tesla: initial experience and validation against microspheres.
AB  - BACKGROUND: Dynamic first pass contrast-enhanced myocardial perfusion is the
      standard CMR method for the estimation of myocardial blood flow (MBF) and MBF
      reserve in man, but it is challenging in rodents because of the high temporal and
      spatial resolution requirements. Hyperemic first pass myocardial perfusion CMR
      during vasodilator stress in mice has not been reported. METHODS: Five C57BL/6 J
      mice were scanned on a clinical 3.0 Tesla Achieva system (Philips Healthcare,
      Netherlands). Vasodilator stress was induced via a tail vein catheter with an
      injection of dipyridamole. Dynamic contrast-enhanced perfusion imaging
      (Gadobutrol 0.1 mmol/kg) was based on a saturation recovery spoiled gradient echo
      method with 10-fold k-space and time domain undersampling (k-t PCA). One week
      later the mice underwent repeat anaesthesia and LV injections of fluorescent
      microspheres at rest and at stress. Microspheres were analysed using confocal
      microscopy and fluorescence-activated cell sorting. RESULTS: Mean MBF at rest
      measured by Fermi-function constrained deconvolution was 4.1 +/- 0.5 ml/g/min and
      increased to 9.6 +/- 2.5 ml/g/min during dipyridamole stress (P = 0.005). The
      myocardial perfusion reserve was 2.4 +/- 0.54. The mean count ratio of stress to
      rest microspheres was 2.4 +/- 0.51 using confocal microscopy and 2.6 +/- 0.46
      using fluorescence. There was good agreement between cardiovascular magnetic
      resonance CMR and microspheres with no significant difference (P = 0.84).
      CONCLUSION: First-pass myocardial stress perfusion CMR in a mouse model is
      feasible at 3 Tesla. Rest and stress MBF values were consistent with existing
      literature and perfusion reserve correlated closely to microsphere analysis. Data
      were acquired on a 3 Tesla scanner using an approach similar to clinical
      acquisition protocols, potentially facilitating translation of imaging findings
      between rodent and human studies.

PMID- 23870735
TI  - Images in emergency medicine. Man with right eye pain.

PMID- 23870736
TI  - Commentary: the primary seat belt survey.

PMID- 23870737
TI  - The perils of the good samaritan.

PMID- 23870738
TI  - Annals of Emergency Medicine Journal Club. Continuing care for patients choosing
      the emergency department as a site for primary care: feasibility, benefits, and
      EMTALA considerations: answers to the March 2013 Journal Club Questions.

PMID- 23870739
TI  - Images in emergency medicine. Two patients with frostbite.

PMID- 23870740
TI  - Effect of cricoid pressure on laryngeal view with the Pentax-AWS.

PMID- 23870741
TI  - In reply.

PMID- 23870742
TI  - Precautions with PERC.

PMID- 23870743
TI  - In reply.

PMID- 23870744
TI  - Use of observation units growing.

PMID- 23870745
TI  - Clinician-performed ultrasonography during the Boston marathon bombing mass
      casualty incident.

PMID- 23870746
TI  - Chronic suppurative otitis media.
AB  - INTRODUCTION: Chronic suppurative otitis media (CSOM) is a common cause of
      hearing impairment and disability. Occasionally it can lead to fatal intracranial
      infections and acute mastoiditis, especially in developing countries. METHODS AND
      OUTCOMES: We conducted a systematic review and aimed to answer the following
      clinical questions: What are the effects of treatments for chronic suppurative
      otitis media in adults and in children? What are the effects of treatments for
      cholesteatoma in adults and in children? We searched: Medline, Embase, The
      Cochrane Library, and other important databases up to May 2010 (Clinical Evidence
      reviews are updated periodically, please check our website for the most up-to
      date version of this review). We included harms alerts from relevant
      organisations such as the US Food and Drug Administration (FDA) and the UK
      Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 51
      systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions: topical
      ear cleansing, surgery for cholesteatoma, systemic antibiotics, topical
      antibiotics, topical antibiotics plus topical corticosteroids, topical
      antiseptics, topical corticosteroids, tympanoplasty (with or without
      mastoidectomy).

PMID- 23870747
TI  - Iranian mothers' selection of a birth method in the context of perceived norms: a
      content analysis study.
AB  - OBJECTIVE: to describe women's perceptions of choosing a particular birth method;
      normal childbirth or caesarean section in the absence of medical indications.
      DESIGN: a descriptive qualitative content analysis was used for data gathering
      and analysis. Interviews were held with 18 pregnant and postnatal women. The
      participants were recruited using a purposive sampling method. Interviews were
      begun with a general question and were followed with specific questions. SETTING:
      three semi-public and public hospitals and two health care centres in an urban
      area of Iran were the locations of data gathering. Data analysis and data
      collection were conducted concurrently and interviews were discontinued when data
      saturation was reached. PARTICIPANTS: the participants consisted of 18 women
      (four pregnant and 14 postnatal) recruited using a purposive sampling method.
      FINDINGS: 'socio-economic and cultural norms' was the main theme that emerged in
      this study. Four other categories comprised the content of interviews: 'cultural
      and religious acceptance', 'social acceptance', 'psychological-social support',
      and 'economical acceptance'. CONCLUSIONS AND IMPLICATIONS: socio-cultural,
      religious and economical norms in the Iranian society play main roles in the
      selection of the birth method by Iranian women. Health care policy-makers are
      expected to attend to the factors influencing women's decision-making on the
      childbirth method to reduce the number of unnecessary caesarean sections.

PMID- 23870748
TI  - Associations of life events during pregnancy with longitudinal change in symptoms
      of antenatal anxiety and depression.
AB  - OBJECTIVE: to investigate the association of life events during pregnancy with
      change in antenatal anxiety and depression symptoms. We distinguished pregnancy
      related and non-pregnancy related events and assessed specificity of these
      associations for depressive or anxious symptoms. In addition, we investigated
      whether the associations were affected by personality or childhood adversities.
      DESIGN: observational prospective cohort study SETTING: primary and secondary
      obstetric care centres in the Netherlands PARTICIPANTS: 1603 women during their
      first trimester of pregnancy between May 2010 and May 2012 MEASUREMENTS AND
      FINDINGS: we performed linear regression analyses to test the associations of
      pregnancy related, non-pregnancy related life events, childhood adversities and
      the personality traits neuroticism and extraversion with the change in symptoms
      of anxiety (State Trait Anxiety Inventory) and depression (Edinburgh Postnatal
      Depression Scale) from week 12 to week 36. Life events during pregnancy were
      associated with increasing antenatal symptoms of anxiety and depression. Effect
      sizes associated with the highest numbers of events observed ranged from 0.59 to
      1.31. Pregnancy related events were specifically associated with increasing
      symptoms of anxiety (p=0.009), whereas non-pregnancy related events were merely
      associated with an increase in symptoms of depression (p<0.001). Neither
      personality traits nor childhood trauma influenced the associations under study.
      KEY CONCLUSIONS: the most important finding is that pregnancy related life events
      during pregnancy increase levels of antenatal anxiety, whereas depression levels
      increase when women experience life events that are unrelated to pregnancy.
      Furthermore, non-pregnancy related events show stronger associations with
      increases in symptoms of anxiety or depression compared to pregnancy related
      events. IMPLICATIONS FOR PRACTICE: our findings may help midwives to tailor
      psychosocial care to the specific risks of the pregnant woman which may
      eventually have a positive impact on the health of mother and child.

PMID- 23870749
TI  - Cajal, Golgi, Nansen, Schafer and the neuron doctrine.
AB  - The Nobel Prize for Physiology or Medicine of 1906 was shared by the Italian
      Camillo Golgi and the Spaniard Santiago Ramon y Cajal for their contributions to
      the knowledge of the micro-anatomy of the central nervous system. In his Nobel
      Lecture, Golgi defended the going-out-of-favour Reticular Theory, which stated
      that the nerve cells--or neurons--are fused together to form a diffuse network.
      Reticularists like Golgi insisted that the axons physically join one nerve cell
      to another. In contrast, Cajal in his lecture said that his own studies confirmed
      the observations of others that the neurons are independent of one another, a
      fact which is the anatomical basis of the now-accepted Neuron Doctrine (Theory).
      This much is well documented. Less well known, however, is the fact that evidence
      against the Reticular Theory had been mounting for some time prior to the Nobel
      Lecture. The Norwegian Fridtjof Nansen had reported in 1887 that, in his studies
      of the primitive creatures he studied in the sea near Bergen, he found no
      connections between the processes of the ganglion cells in their nervous systems.
      Nor is it adequately appreciated that ten years earlier, in 1877, the Englishman
      Edward Schafer had similarly described seeing no connections between the nerve
      elements in the mantles of the jellyfish. This paper begins by charting the
      research that led directly to the awarding of the 1906 Nobel Prize. It then shows
      that long before the ultimate vindication of the Neuron Doctrine, researchers in
      several countries had been accumulating evidence that undermined or contradicted
      the Reticular Theory.

PMID- 23870750
TI  - Systemic signaling during plant defense.
AB  - Systemic acquired resistance (SAR) is a type of pathogen-induced broad-spectrum
      resistance in plants. During SAR, primary infection-induced rapid generation and
      transportation of mobile signal(s) 'prepare' the rest of the plant for subsequent
      infections. Several, seemingly unrelated, mobile chemical inducers of SAR have
      been identified, at least two of which function in a feed-back regulatory loop
      with a lipid transfer-like protein. Signal(s) perception in the systemic tissues
      relies on the presence of an intact cuticle, the waxy layer covering all aerial
      parts of the plant. SAR results in chromatin modifications, which prime systemic
      tissues for enhanced and rapid signaling derived from salicylic acid, which along
      with its signaling components is key for SAR induction. This review summarizes
      recent findings related to SAR signal generation, movement, and perception. 

PMID- 23870751
TI  - Perceptual-motor abilities in pre-school preterm children.
AB  - BACKGROUND: Several studies report a high percentage of premature infants
      presenting perceptual motor difficulties at school age. The new version of the
      Movement Assessment Battery for Children allows the assessment of perceptual
      motor abilities in children from the age of 3years. AIMS: To evaluate early
      perceptual-motor abilities in prematurely born children below the age of 4years.
      STUDY DESIGN: The Movement Assessment Battery for Children 2nd edition was
      administered to 105 low-risk prematurely born children (<32weeks gestation) and
      in a control group of 105 term-born children matched for age and sex. All
      children were assessed between the age of 3years and 3years-11months. RESULTS: 63
      children (60%) had total scores above the 15th percentile, 15 (14.3%) had scores
      between the 5th and the 15th percentile, and 13 (12.4%) below the 5th percentile.
      The remaining 14 children (13.3%) refused to perform or to complete the test. The
      difference between preterm and control group was significant for total scores,
      Manual Dexterity and Aiming and Catching scores. In the preterm group there was a
      correlation between age at testing, total scores and Aiming and Catching
      subscores. The Movement ABC-2 subscores were significantly lower in children born
      below 29weeks. CONCLUSION: Perceptual-motor difficulties can already be detected
      on the assessment performed before the age of 4years. Prematurely born children
      assessed between 3years and 3years-3months appeared to have more difficulties in
      performing the test than the older ones or their age matched term-born peers.
      These findings support the possibility of a delayed maturation in the younger age
      group.

PMID- 23870753
TI  - Does genomic selection have a future in plant breeding?
AB  - Plant breeding largely depends on phenotypic selection in plots and only for
      some, often disease-resistance-related traits, uses genetic markers. The more
      recently developed concept of genomic selection, using a black box approach with
      no need of prior knowledge about the effect or function of individual markers,
      has also been proposed as a great opportunity for plant breeding. Several
      empirical and theoretical studies have focused on the possibility to implement
      this as a novel molecular method across various species. Although we do not
      question the potential of genomic selection in general, in this Opinion, we
      emphasize that genomic selection approaches from dairy cattle breeding cannot be
      easily applied to complex plant breeding. 

PMID- 23870752
TI  - Social competence of preschool children born very preterm.
AB  - BACKGROUND: Relatively little is known about the early social development of
      children born very preterm despite clear suggestions of later interpersonal
      difficulties. AIMS: To compare the social competence of very preterm (VPT) and
      full term (FT) born children at age 4 and identify infant, social and family
      factors associated with later risk. STUDY DESIGN: Prospective longitudinal study.
      SUBJECTS: A regionally representative cohort of 103 VPT (<= 32 weeks gestation)
      children and a comparison group of 105 FT children (36-41 weeks gestation) born
      between 1998 and 2000. OUTCOME MEASURES: At corrected age 4 years, a range of
      parent report, observational and laboratory measures assessed children's
      emotional and behavioral adjustment, emotional regulation, social interactive
      behavior and theory of mind understanding. Extensive perinatal, social background
      and family functioning data were also available from birth to age 4. RESULTS:
      Compared to their FT peers, VPT born children had poorer emotional and behavioral
      adjustment, were less effective in regulating their emotions, had lower levels of
      positive peer play and had less synchronous interactions with their parents.
      Within the VPT group, predictors of poor social competence included family
      socioeconomic disadvantage, extreme prematurity, severity of cerebral white
      matter abnormalities and early childhood exposure to high levels of maternal
      anxiety and negative parenting. CONCLUSIONS: VPT pre-schoolers are characterized
      by a range of subtle social difficulties likely to adversely affect their ability
      to establish and maintain positive relationships with others. These difficulties
      need to be monitored alongside other potential neurodevelopmental concerns and
      parents supported to actively nurture child social competence.

PMID- 23870755
TI  - Meningoencephalocele of the temporal bone: pictorial essay on transmastoid
      extradural-intracranial repair.
AB  - PURPOSE: A spontaneous meningoencephalocele of the temporal bone may present with
      effusion in the middle ear, a cerebrospinal fluid leak, hearing loss, or rarely
      otitic meningitis. Repair of spontaneous encephaloceles in the temporal bone has
      been performed using transmastoid and transcranial middle fossa approaches or a
      combination of the two with varied results. The authors present a technical paper
      on the transmastoid extradural intracranial approach for the management of
      temporal lobe encephaloceles. MATERIALS/METHODS: Case reports and cadaver
      dissections are used to provide a pictorial essay on the technique. Advantages
      and disadvantages compared with alternative surgical approaches are discussed.
      RESULTS: Traditional transmastoid approaches are less morbid compared with a
      transcranial repair as they avoid brain retraction. However, in the past, there
      has been a higher risk of graft failure and hearing loss due to downward graft
      migration and a potential need for ossicular disarticulation. For the appropriate
      lesion, the transmastoid extradural intracranial approach lesion offers a stable
      meningoencephalocele repair without the comorbidity of brain retraction.
      CONCLUSION: The authors describe a transmastoid extradural intracranial technique
      via case reports and cadaver dissections for the repair of spontaneous
      meningoencephalocele defects larger than 2 cm. This approach provides more
      support to the graft compared to the conventional transmastoid repair.

PMID- 23870756
TI  - Advances in anticancer radiopharmaceuticals.
AB  - This review highlights recent progress in the development of anticancer
      radiopharmaceuticals. Molecularly targeted radiotherapy refers to the selective
      delivery of radionuclides that emit charged particles, such as alpha particles,
      beta or Auger electrons, to cancer cells via a targeting vector. The discovery of
      new molecular targets through systems biology and other approaches has widened
      the scope for radiopharmaceutical development. Innovations in antibody
      engineering and humanisation, recombinant DNA technology, conjugation chemistry
      and, increasingly, nanotechnology have provided new approaches to the delivery of
      radionuclides to cancer cells. The increased availability of radioisotopes that
      have not traditionally been considered for therapy, such as alpha particle
      emitters, has also broadened the indications for targeted radiotherapy. 

PMID- 23870757
TI  - Biomarkers of radiation exposure: can they predict normal tissue
      radiosensitivity?
AB  - Late adverse tissue reactions affect up to a fifth of cancer patients receiving
      radiotherapy, with several clinical parameters known to influence normal tissue
      responses. Despite careful control of treatment-related parameters, a significant
      component of inter-individual variability in normal tissue responses remains
      unaccounted for, suggesting that perhaps intrinsic genetic and epigenetic factors
      are the major determinants of normal tissue effects. Against this background,
      research was initiated into cellular markers predictive of clinical
      radiosensitivity, focusing first on colony-forming assays, before the advent of
      reliable surrogate end points, such as chromosomal radiosensitivity and DNA
      damage repair. More recently, collaborative efforts have focused on genotyping
      analysis at a target gene or whole genome level. Despite early positive reports
      from several small-scale pilot studies testing these assays, subsequent attempts
      to reproduce comparable levels of association between the cellular markers and
      clinical phenotype in larger cohorts have frequently been inconclusive, although
      the first well-replicated studies are beginning to emerge. Here, we discuss the
      underlying rationale, consider aspects pertaining to patient recruitment and
      study design, review some of the reported findings for DNA damage-related
      markers, and highlight some of the limitations and confounding factors affecting
      tests of association between predictive markers and clinical radiosensitivity. We
      propose that an integrative approach incorporating multiple assays involving
      collaborations across centres, together with prospective meticulous recruitment
      of patients taking into account modifying clinical factors of normal tissue
      responses, enhances the chance of finding the long sought after markers of
      individual radiosensitivity. 

PMID- 23870758
TI  - beta-Keto esters from ketones and ethyl chloroformate: a rapid, general,
      efficient synthesis of pyrazolones and their antimicrobial, in silico and in
      vitro cytotoxicity studies.
AB  - BACKGROUND: Pyrazolones are traditionally synthesized by the reaction of beta
      keto esters with hydrazine and its derivatives. There are methods to synthesize
      beta-keto esters from esters and aldehydes, but these methods have main
      limitation in varying the substituents. Often, there are a number of methods such
      as acylation of enolates in which a chelating effect has been employed to lock
      the enolate anion using lithium and magnesium salts; however, these methods
      suffer from inconsistent yields in the case of aliphatic acylation. There are
      methods to synthesize beta-keto esters from ketones like caboxylation of ketone
      enolates using carbon dioxide and carbon monoxide sources in the presence of
      palladium or transition metal catalysts. Currently, the most general and simple
      method to synthesize beta-keto ester is the reaction of dimethyl or ethyl
      carbonate with ketone in the presence of strong bases which also requires long
      reaction time, use of excessive amount of reagent and inconsistent yield. These
      factors lead us to develop a simple method to synthesize beta-keto esters by
      changing the base and reagent. RESULTS: A series of beta-keto esters were
      synthesized from ketones and ethyl chloroformate in the presence of base which in
      turn are converted to pyrazolones and then subjected to cytotoxicity studies
      towards various cancer cell lines and antimicrobial activity studies towards
      various bacterial and fungal strains. CONCLUSION: The beta-keto esters from ethyl
      chloroformate was successfully attempted, and the developed method is simple,
      fast and applicable to the ketones having the alkyl halogens, protecting groups
      like Boc and Cbz that were tolerated and proved to be useful in the synthesis of
      fused bicyclic and tricyclic pyrazolones efficiently using cyclic ketones. Since
      this method is successful for different ketones, it can be useful for the
      synthesis of pharmaceutically important pyrazolones also. The synthesized
      pyrazolones were subjected to antimicrobial, docking and cytotoxicity assay
      against ACHN (human renal cell carcinoma), Panc-1 (human pancreatic
      adenocarcinoma) and HCT-116 (human colon cancer) cell line, and lead molecules
      have been identified. Some of the compounds are found to have promising activity
      against different bacterial and fungal strains tested.

PMID- 23870759
TI  - Spermatozoa concentration influences cryopreservation success in sea trout (Salmo
      trutta m. trutta L.).
AB  - Variation among individuals is substantial for spermatozoa concentration in fresh
      milt in sea trout (Salmo trutta m. trutta L.). The objective of the present study
      was to examine effects of spermatozoa concentration in this species on subsequent
      cryopreservation success. Milt with high spermatozoa concentration was diluted
      with seminal plasma to obtain concentrations ranging between 6 and 24 * 10(9) mL(
      1) with steps of 2 * 10(9) mL(-1). Diluted milts were cryopreserved in 0.25-mL
      straws with extender (0.3 M glucose) containing 10% methanol and 10 % (vol/vol)
      supplement of hen egg yolk. The dilution ratio was 1:3 (milt:cryomedium).
      Cryopreservation efficacies were assessed according to evaluation of motility of
      frozen/thawed spermatozoa and quantification of fertilizing ability. Percentage
      of motility of frozen/thawed spermatozoa was influenced by spermatozoa
      concentration in the cryomedium (P < 0.05). The highest motility was observed in
      samples with 3.0 to 4.0 * 10(9) spermatozoa per mL of cryomedium, which
      corresponds to 12 to 16 * 10(9) spermatozoa per mL in fresh milt. Higher sperm
      concentrations and lower sperm concentrations in cryomedium reduced the
      effectiveness of cryopreservation when compared with the optimum.
      Cryopreservation success measured according to fertilization rate was in
      agreement with results for motility of frozen/thawed spermatozoa, but the optimum
      could not be determined with statistical precision because of differences in
      fertilization rate among individual donor males. However, a significant positive
      correlation was found between postthaw motility and fertilization rate and
      between cryopreserved spermatozoa velocity and fertilization rate (P < 0.05). In
      sea trout, cryopreservation efficiency is influenced by spermatozoa concentration
      in cryomedium. Individual adjustment of the dilution ratio, based on initial
      spermatozoa density, is recommended in the freezing protocol. Maximum
      cryoresistance of the cell was obtained when spermatozoa concentration in
      cryomedium ranged from 3.0 to 4.0 * 10(9) mL(-1). 

PMID- 23870760
TI  - Metastatic tumours to the head and neck: retrospective analysis from a Brazilian
      tertiary referral centre.
AB  - Data regarding the development of head and neck metastases are limited, with the
      majority of the studies focusing on single cases affecting mainly the oral cavity
      and surrounding tissues. This study describes the incidence of head and neck
      metastases from primary tumours originating elsewhere. The medical records of
      selected patients were reviewed, and socio-demographic data as well as
      information about the localization of the primary tumours and their metastases to
      this region, treatment modalities employed, follow-up, and outcomes were
      collected. A total of 24 cases were found. The mean age at diagnosis was 52.1+/
      17.6 years and the male to female ratio was 1:1.4. Most primary tumours were
      located in the lung and breast. The overall 1-, 2-, and 5-year survival rates
      were 63.0%, 39.1%, and 19.6%, respectively. Radiotherapy for the metastatic focus
      significantly prolonged the survival time of the patients (P=0.048). Cervical
      lymph node metastases are a common event in patients with primary tumours growing
      elsewhere. 

PMID- 23870761
TI  - Clinical commentary in response to "effectiveness of cast immobilization in
      comparison to the gold-standard self-removal orthotic intervention for closed
      mallet fingers: a randomized clinical trial".

PMID- 23870762
TI  - Clinical effects and antivenom use for snake bite victims treated at three US
      hospitals in Afghanistan.
AB  - OBJECTIVE: Annually, more than 100,000 US and international military and civilian
      personnel work in Afghanistan within terrain harboring venomous snakes. Current
      literature insufficiently supports Afghan antivenom treatment and stocking
      guidelines. We report the clinical course and treatments for snakebite victims
      presenting to US military hospitals in Afghanistan. METHODS: All snakebite
      victims presenting to 3 US military emergency departments between July 2010 and
      August 2011 in northern and southern Afghanistan were examined via chart review.
      Case information included patient demographics, snake description, bite details
      and complications, laboratory results, antivenom use and adverse effects,
      procedures performed, and hospital course. RESULTS: Of 17 cases, median patient
      age was 20 years (interquartile range [IQR], 12-30), 16 were male, and 82% were
      Afghans. All bites were to an extremity, and median time to care was 2.8 hours
      (IQR, 2-5.8). On arrival, 8 had tachycardia and none had hypotension or hypoxia.
      A viper was implicated in 5 cases. Ten cases received at least 1 dose of
      polyvalent antivenom, most commonly for coagulopathy, without adverse effects.
      Six received additional antivenom, 6 had an international normalized ratio (INR)
      > 10, and none developed delayed coagulopathy. Three received blood transfusions.
      Hospital stay ranged from 1 to 4 days. None required vasopressors, fasciotomy, or
      other surgery, and none died. All had resolution of marked coagulopathies and
      improved swelling and pain on discharge. CONCLUSIONS: We report the largest
      series of snake envenomations treated by US physicians in Afghanistan. Antivenom
      was tolerated well with improvement of coagulopathy and symptoms. All patients
      survived with minimal advanced interventions other than blood transfusion.

PMID- 23870764
TI  - Patterns of game animal attacks on hunters in Croatia over a 13-year period.
AB  - Hunter-game animal conflicts are occasionally reported from various parts of the
      world. This case series comprises all 7 game animal attacks on hunters reported
      to the Croatian Hunting Association over a period of 13 years (1999-2011),
      covering the entire Croatian territorial area. Seasonally, attacks occurred most
      frequently in the winter time, when the hunting season is at its peak. The most
      common attacking animal, representing 5 of 7 cases (71.4%), was the wild boar,
      and the majority of the attacks happened in the morning. All of our victims were
      male, with an average age of 51 years (range 26 to 69 years). Six victims
      sustained a bite wound or wounds and 1 was rammed by the animal. Almost all of
      our patients (5 of 7, with one unknown) recovered completely and without
      significant complications. 

PMID- 23870763
TI  - Exercising in a hot environment: which T-shirt to wear?
AB  - OBJECTIVE: The aim of this study was to investigate thermoregulatory,
      cardiorespiratory, metabolic, and perceptual responses while running in a hot
      environment (31.7 degrees  +/- 1.0 degrees C; 42% +/- 3% relative humidity) and
      wearing T-shirts made from different fiber types. METHODS: Eight well-trained men
      performed 4 tests wearing either a T-shirt made of 100% polyester with 4, 6, or 8
      channels, or one made of 100% cotton. Each test consisted of 30 minutes running
      at 70% of peak oxygen uptake, followed by a ramp test to exhaustion and 15
      minutes of recovery. RESULTS: There were no differences in skin, core, and body
      temperatures between fiber types during submaximal and high-intensity running
      (best P = .08). During recovery, body temperature and shivering/sweating
      sensations were lower when wearing 4- and 6-channel fibers (P <= .04) compared
      with cotton. The relative humidity at the chest and back were lower for all
      polyester T-shirts compared with cotton during and after submaximal and maximal
      running (P <= .007). Heart rate (best P = .10), oxygen uptake (P = .95),
      respiratory exchange ratio (best P = .93), ventilation (best P = .99), and blood
      lactate concentration (best P = .97) did not differ between the fiber types. Nor
      were any differences in time to exhaustion (best P = .76), ratings of perceived
      exertion (best P = .09), thermal sensation (best P = .07), or sensation of
      clothing wetness (best P = .36) discovered. CONCLUSIONS: Although statistical
      analysis revealed lower shivering/sweating sensations while wearing 4- and 6
      channel fiber shirts during recovery, with an improved chest and back
      microenvironment for all polyester T-shirts, the question remains whether these
      differences are of any practical relevance because the performance of the well
      trained men was unaffected.

PMID- 23870765
TI  - Painful sting after exposure to Dendrocnide sp: two case reports.

PMID- 23870766
TI  - Injuries in commercial whitewater rafting on the New and Gauley rivers of West
      Virginia.
AB  - OBJECTIVE: To describe the rates, patterns, and likelihood of injuries in
      commercial whitewater rafting on the New and Gauley rivers, West Virginia.
      METHODS: Standardized injury report forms developed by the West Virginia
      Whitewater Commission were reviewed for years 2005-2010 to provide a statistical
      account of injuries reported by licensed commercial rafting outfitters operating
      on the New and Gauley rivers. RESULTS: Overall, musculoskeletal injuries
      (sprains/strains, 21.1%; dislocations, 13.8%; fractures, 12.2%) comprised the
      majority (47.4%) of incidents followed by injuries to soft tissue (lacerations,
      29.0%; abrasions, 13.3%; contusions, 2.3%). Almost one half (44.3%) of injuries
      were to the head, neck, and shoulders followed by the lower extremities
      (foot/ankle/leg/knee/hip, 33.9%) and upper extremities (hand/wrist/arm, 14.3%).
      Data analyzed using the Somers' D statistic revealed the likelihood of an injury
      occurring inside the raft is P = .55, and P = .39 when passengers are ejected
      from the raft into the river. The most likely injuries to occur to passengers are
      a laceration (P = .51) or a sprain (P = .20). The main probabilities for the
      risks of injuries were found to be to the head (P = .24), shoulder (P = .16), and
      face (P = .13) of the passenger. CONCLUSIONS: By knowing what injuries are
      common, their likelihood of occurrence, and the settings in which they happen,
      commercial outfitters can initiate practices to reduce injury rates.

PMID- 23870767
TI  - Adolescent pediatric pain tool for multidimensional measurement of pain in
      children and adolescents.
AB  - Very few multidimensional tools are available for measurement of pain in children
      and adolescents. We critically reviewed the scientific literature to examine the
      psychometrics and utility of the Adolescent Pediatric Pain Tool (APPT), a
      multidimensional self-report tool that evaluates the intensity, location, and
      quality (including affective, evaluative, sensory, and temporal) dimensions of
      pain. The APPT is available in English and Spanish for children and adolescents,
      and was modeled after the McGill Pain Questionnaire in adults. We found good
      evidence for construct validity, reliability, and sensitivity of the APPT for the
      measurement of pediatric pain. The APPT was used to measure pain in children with
      different conditions, such as cancer, sickle cell disease, orthopedic, traumatic
      injuries, and allergy testing. Although the APPT was designed to assess the
      multiple dimensions of pain, the majority of the reports included results only
      for the intensity ratings. Unlike the numerical and pediatric faces rating
      scales, which are widely used in clinical practice and research, the APPT is not
      limited to the single dimension of pain intensity. It measures multiple
      dimensions, and may be able to discriminate between nociceptive and neuropathic
      pain. The APPT is one of a few multidimensional pain measures that can help to
      advance the science of pediatric pain and its management. When the APPT is used
      in practice or research, the multiple dimensions of pain may be characterized and
      compared in different painful conditions. It may guide the use of multimodal
      interventions in children and adolescents with a variety of pain conditions. 

PMID- 23870768
TI  - Collaborative overexpression of matrix metalloproteinase-1 and vascular
      endothelial growth factor-C predicts adverse prognosis in patients with gliomas.
AB  - BACKGROUND AND AIM: Matrix metalloproteinase-1 (MMP-1), a member of the MMP
      family of zinc-dependent endopeptidases, has been detected to be strongly
      expressed in gliomas with high tumor grade and to be correlated with increased
      tumor invasiveness. Vascular endothelial growth factor-C (VEGF-C), which is able
      to induce MMP-1 transcription, has been found to be upregulated in glioblastoma
      compared to low grade gliomas and non-neoplastic brain. The aim of the present
      study was to investigate the clinical significance of the co-expression of MMP-1
      and VEGF-C in glioma patients on determining the prognosis. METHODS: One hundred
      and sixteen glioma patients (26 World Health Organization (WHO) grade I, 30 WHO
      grade II, 30 WHO grade III, and 30 WHO grade IV) and 15 non-neoplastic brain
      specimens acquired from 15 patients undergoing surgery for epilepsy as control
      were collected. Immunohistochemistry was used to evaluate the expression of MMP-1
      and VEGF-C in glioma and non-neoplastic brain tissues. The correlations of
      collaborative MMP-1 and VEGF-C expression with selected clinicopathologic
      parameters and clinical outcome of glioma patients were also assessed. RESULTS:
      Both MMP-1 and VEGF-C expression were significantly higher in glioma tissues
      compared to non-neoplastic brain tissues (both P<0.001). Of 116 glioma patients,
      68 (58.62%) overexpressed MMP-1 and VEGF-C simultaneously. In addition, combined
      MMP-1 and VEGF-C expression was significantly associated with WHO grade (P<0.001)
      and Karnofsky performance status (KPS) score (P=0.01). Moreover, glioma patients
      expressing both MMP-1 and VEGF-C exhibited markedly poorer overall survival
      (P<0.001). According to the multivariate analyses, collaborative overexpression
      of MMP-1 and VEGF-C was found to be an independent prognostic factor for overall
      survival (P=0.009). CONCLUSIONS: Our data demonstrated for the first time that
      overexpression of both MMP-1 and VEGF-C may be an independent poor prognostic
      factor in gliomas, suggesting the interaction between MMP-1 and VEGF-C
      collaboratively stimulated advanced tumor progression and adverse outcome.
      Inhibiting both MMP-1 and VEGF-C could be a novel therapeutic approach for
      gliomas.

PMID- 23870770
TI  - What are we waiting for?

PMID- 23870769
TI  - Fetal echocardiography using HDlive.

PMID- 23870771
TI  - Barriers to the pharmacological treatment of women with psychiatric disorders
      during pregnancy and breastfeeding: results of a survey.

PMID- 23870772
TI  - It sounded like a good idea at the time.

PMID- 23870773
TI  - The use of mesh in pelvic reconstructive surgery.

PMID- 23870774
TI  - The effect of change in a labour management protocol on caesarean section rate in
      nulliparous women.
AB  - OBJECTIVE: To investigate the impact on obstetric outcome in nulliparous women of
      changing labour management from an expectant approach to proactive support of
      labour. METHODS: We conducted a retrospective cohort study in a teaching hospital
      in the Netherlands among 858 women >= 37 weeks' gestation with a singleton fetus
      in cephalic position and spontaneous labour who planned to have a vaginal birth
      in the hospital under the care of an obstetrician. Exclusion criteria were
      gestational age < 37 weeks, induction of labour, primary Caesarean section, non
      cephalic position, and non-Caucasian ethnicity. Labour outcomes in the period
      1999 to 2002 (using an expectant approach) were compared with labour outcomes in
      the period 2008 to 2010 (using proactive support of labour). The primary outcome
      measure was the relationship between the CS rate and the form of labour
      management (expectant approach vs. proactive support). The secondary outcome
      measure was to identify risk factors for repeat CS. RESULTS: The overall
      prevalence of CS in the study population was 12.2%. The CS rate increased
      significantly from 9.7% between 1999 and 2002, to 15.4% between 2008 and 2010 (P
      < 0.001). Meanwhile, the assisted vaginal delivery rate decreased from 22.7% to
      16.7% (P = 0.03). Multiple logistic regression showed that epidural analgesia (OR
      4.6; 95% CI 2.6 to 8.4), occiput posterior position (OR 7.4; 95% CI 4.3 to 12.8),
      and advanced maternal age (OR 1.91; 95% 1.31 to 2.76) were risk factors for CS.
      CONCLUSION: Changing labour management from an expectant approach to proactive
      support of labour did not decrease the Caesarean section rate.

PMID- 23870775
TI  - Fasting capillary glucose as a screening test for ruling out gestational diabetes
      mellitus.
AB  - OBJECTIVE: A common approach to screening for gestational diabetes mellitus (GDM)
      is the testing of all pregnant women with a one-hour, 50 g glucose challenge test
      (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) when the GCT
      is positive (>= 7.8 mmol/L). As only a small subset of those with a positive GCT
      will have GDM, many more women undergo the OGTT than may be necessary. In this
      context, we hypothesized that measurement of fasting capillary glucose (FCG)
      could provide a strategy for reducing the number of unnecessary OGTTs. Thus, we
      sought to identify a threshold level of FCG below which GDM could be ruled out
      following a positive GCT, without need for the OGTT. METHODS: Following a
      positive GCT, 888 women underwent measurement of FCG prior to their OGTT. We
      evaluated the test characteristics of FCG for identifying the 209 women diagnosed
      with GDM on the OGTT. RESULTS: Fasting capillary glucose was positively
      associated with each glucose measurement on the OGTT (all P < 0.001) and
      inversely related to insulin sensitivity and pancreatic beta-cell function (both
      P < 0.001). As FCG increased, the prevalence of GDM progressively rose (P <
      0.001). However, the area under the curve of the receiver-operating
      characteristic curve for FCG in predicting GDM was modest (0.67). Although using
      an FCG threshold of 4.8 mmol/L could reduce the number of OGTTs by 28.4%, this
      approach would miss 18.2% of cases of GDM. CONCLUSION: Fasting capillary glucose
      is associated with glycemia, insulin sensitivity, and pancreatic beta-cell
      function. However, a single FCG measurement is insufficient for reliably ruling
      out GDM after an abnormal GCT.

PMID- 23870776
TI  - A new method of positioning at delivery compared with the dorsal recumbent
      position: an exploratory retrospective study of obstetric outcomes.
AB  - BACKGROUND: In the last 30 years, several initiatives have aimed to reintroduce a
      certain freedom in positioning during labour. The objective of this study was to
      compare an alternative method of positioning at delivery (APOR B method) with the
      dorsal recumbent (supine) position. METHODS: We undertook a comparative,
      retrospective study of 276 singleton deliveries at >= 36 weeks. The APOR B method
      used by two general practitioners (GPs) was compared with the dorsal recumbent
      position used by two other GPs with similar years of experience. We assessed
      obstetric outcomes with logistic regression analyses. RESULTS: The study
      populations were similar except for more cases of induced labour (40% vs. 27%, P
      = 0.030) and earlier gestational age at delivery (mean +/- SD 39.1 +/- 1.4 vs.
      39.4 +/- 1.0 weeks of amenorrhea, P = 0.032) in the APOR B group (adjustment
      provided). Mode of delivery and perineal outcomes were similar, with 74% and 72%
      (P = 0.816) of spontaneous vaginal deliveries and 38% and 44% (P = 0.368) of
      intact perineums for APOR B and dorsal recumbent positions, respectively. Women
      in the APOR B group were less likely to have vaginal tears (15% vs. 28%, aOR
      0.45, 95% CI 0.23 to 0.89). No differences were observed in the frequency of
      abnormal fetal heart rate, Apgar score < 7 at five minutes, dystocia, and blood
      loss. However, umbilical cord arterial pH < 7.20 was more frequent in the APOR B
      group (32% vs. 20%, aOR 2.0, 95% CI 1.1 to 3.8). CONCLUSION: The outcomes of the
      two methods of positioning at delivery were mostly equivalent, except for fewer
      vaginal tears and lower umbilical cord arterial pH in the APOR B group. These
      findings will need to be further assessed in randomized controlled trials.

PMID- 23870777
TI  - Quantitative sensory testing in gynaecology: improving preoperative and
      postoperative pain diagnosis.
AB  - Chronic pelvic pain presents difficulties for women suffering its complex
      presentation. It also presents difficulties for clinicians involved in diagnosing
      and managing the problem. We review here clinically relevant information related
      to visceral pathology and its association with peripheral and central aspects of
      pain hypersensitivity. We address why surgery appears to be successful in some
      cases but less than successful in others, and what cautionary indicators should
      be taken into account. A categorization of chronic pelvic pain based on our
      understanding of pain physiology and mechanisms involved is proposed. The
      benefits of multidimensional sensory and pain testing in gynaecological care are
      reviewed. 

PMID- 23870778
TI  - Incarcerated fibroid uterus: the role of conservative management.
AB  - BACKGROUND: Uterine incarceration occurs when the gravid uterus remains trapped
      within the sacral hollow and cannot ascend out of the pelvis as it enlarges.
      Predisposing factors include uterine fibroids. Optimal management of uterine
      incarceration involves manual reduction of the uterus because of the significant
      maternal and fetal risks associated with persistent incarceration. CASE: A
      nulliparous woman with known uterine incarceration secondary to a large anterior
      uterine fibroid was managed conservatively throughout her pregnancy after
      attempts at manual reduction were unsuccessful. CONCLUSION: Conservative
      management of the incarcerated uterus is a reasonable option if attempts at
      manual reduction are unsuccessful. Magnetic resonance imaging can be helpful in
      delineating anatomy and planning for delivery.

PMID- 23870779
TI  - Are Canadian postgraduate training programs meeting the health advocacy needs of
      obstetrics and gynaecology residents?
AB  - OBJECTIVES: Health advocacy (HA) is a core competency in Canadian obstetrics and
      gynaecology postgraduate programs. Our objectives were to assess awareness and
      understanding of the health advocate role among trainees, their current HA
      training and exposure, and the desire and needs for future HA training. METHODS:
      An anonymous, cross-sectional, Internet-based, self-reported health advocacy
      questionnaire was distributed to Canadian obstetrics and gynaecology trainees.
      Descriptive analysis was conducted for all study variables. Chi-square tests,
      Cochran-Armitage trend test, and Fisher exact test were performed where
      appropriate. RESULTS: Most trainees (93.9% of respondents) were aware of the
      CanMEDS HA role and that it is a training objective (92.9%). Only 52.4% had clear
      objectives while 58.4% understood the role requirements. Most trainees (95.1% of
      respondents) felt HA was important to address during training. Only 30.4% had HA
      training, and just 36.3% felt their training needs were addressed. Training
      included teaching sessions (11.9%), clinical teaching (4.7%), and role modelling
      (4.7%). Although 82.9% of respondents had HA opportunities with patients, there
      were fewer opportunities at community (45.1%) and societal (30.0%) levels.
      Awareness of community groups and activities was low (28.6%), and few (20.0%) had
      participated in community advocacy programs during their residency. Incorporating
      advocacy activities into training was valued (80.0%). Many residents supported
      mandatory HA training (60.0%), more training time on HA experiences (66.3%), and
      HA experiences during protected time (71.3%). CONCLUSION: Awareness of and
      interest in the HA role is high, but clear objectives and training are lacking or
      inadequate. A standardized curriculum would ensure health advocacy exposure and
      emphasize active participation in community and societal activities. Trainees
      support this training during protected time.

PMID- 23870780
TI  - Looking to the future of obstetrics and gynaecology training in Canada: a
      resident's perspective.

PMID- 23870782
TI  - Plasmonic bandgap in random media.
AB  - We present a dispersion theory of the surface plasmon polaritons (SPP) in random
      metal-dielectric nanocomposite (MDN) consisting of bulk metal embedded with
      dielectric inclusions. We demonstrate that embedding of dielectric nanoparticles
      in metal results in the formation of the plasmonic bandgap due to strong coupling
      of the SPP at the metal-vacuum interface and surface plasmons localized at the
      surface of nanoinclusions. Our results show that MDN can replace metals in
      various plasmonic devices, which properties can be tuned in a wide spectral
      range. Being compatible with waveguides and other photonic structures, MDN offers
      high flexibility in the plasmonic system design. 

PMID- 23870781
TI  - Health professionals working with First Nations, Inuit, and Metis consensus
      guideline.
AB  - OBJECTIVE: Our aim is to provide health care professionals in Canada with the
      knowledge and tools to provide culturally safe care to First Nations, Inuit, and
      Metis women and through them, to their families, in order to improve the health
      of First Nations, Inuit, and Metis. EVIDENCE: Published literature was retrieved
      through searches of PubMed, CINAHL, Sociological Abstracts, and The Cochrane
      Library in 2011 using appropriate controlled vocabulary (e.g.,cultural
      competency, health services, indigenous, transcultural nursing) and key words
      (e.g., indigenous health services, transcultural health care, cultural safety).
      Targeted searches on subtopics (e.g., ceremonial rites and sexual coming of age)
      were also performed. The PubMed search was restricted to the years 2005 and later
      because of the large number of records retrieved on this topic. Searches were
      updated on a regular basis and incorporated in the guideline to May 2012. Grey
      (unpublished) literature was identified through searching the websites of
      selected related agencies (e.g., Campbell Collaboration, Social Care Online,
      Institute for Healthcare Improvement). VALUES: The quality of evidence in this
      document was rated using the criteria described in the Report of the Canadian
      Task force on Preventive Health Care (Table).

PMID- 23870783
TI  - Are there any laws in biology?: comment on "How life changes itself: the Read
      Write (RW) genome" by James Shapiro.

PMID- 23870784
TI  - The watchmaker is blind but he is not stupid: comment on "How life changes
      itself: the Read-Write (RW) genome" by James Shapiro.

PMID- 23870785
TI  - Energy expenditure and nutritional status in pediatric patients before and after
      lung transplantation.
AB  - Resting energy expenditure and nutritional status in pediatric patients was
      determined before and then 1 and 2 years after lung transplantation. Mean resting
      energy expenditure was increased (132%) before transplantation and declined
      (112%) after transplantation. Body mass index and weight z-scores improved
      posttransplantation, but nutritional measurements remained below normal
      population values.

PMID- 23870786
TI  - Implications of bioactive solute transfer from hosts to parasitic plants.
AB  - Parasitic plants--which make their living by extracting nutrients and other
      resources from other plants--are important components of many natural ecosystems;
      and some parasitic species are also devastating agricultural pests. To date, most
      research on plant parasitism has focused on nutrient transfer from host to
      parasite and the impacts of parasites on host plants. Far less work has addressed
      potential effects of the translocation of bioactive non-nutrient solutes-such as
      phytohormones, secondary metabolites, RNAs, and proteins-on the development and
      physiology of parasitic plants and on their subsequent interactions with other
      organisms such as insect herbivores. A growing number of recent studies document
      the transfer of such molecules from hosts to parasites and suggest that they may
      have significant impacts on parasite physiology and ecology. We review this
      literature and discuss potential implications for management and priorities for
      future research.

PMID- 23870787
TI  - Erythropoietin corrects thrombocytopenia.

PMID- 23870788
TI  - Holiday heart block: alcohol-induced PR prolongation.

PMID- 23870789
TI  - Cancer survivorship, a unique and growing cohort in medical practice: radiology
      perspective.
AB  - The unique medical and psychologic burdens of cancer survivorship have only
      recently been recognized. This rapidly expanding cohort of patients will be seen
      increasingly by non-oncology physicians who must consider medical issues related
      to their cancer or its therapy for any presenting symptoms. Appropriate use of
      clinical imaging is essential for diagnosing treatment-related complications,
      recurrent tumor, or emergence of second primaries. This article will review
      clinical imaging in common medical problems uniquely found in cancer survivors.

PMID- 23870790
TI  - The assassin: Chagas cardiomyopathy.

PMID- 23870791
TI  - Early diagnosis of myocardial infarction using absolute and relative changes in
      cardiac troponin concentrations.
AB  - BACKGROUND: Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT)
      seem to have higher diagnostic accuracy in the early diagnosis of acute
      myocardial infarction compared with relative changes. It is unknown whether the
      same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether
      the combination of absolute and relative change might further increase accuracy.
      METHODS: In a prospective, international multicenter study, high-sensitivity
      cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche
      Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif;
      hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after
      1 and 2 hours in a blinded fashion in 830 unselected patients with suspected
      acute myocardial infarction. The final diagnosis was adjudicated by 2 independent
      cardiologists. RESULTS: The area under the receiver operating characteristic
      curve for diagnosing acute myocardial infarction was significantly higher for 1-
      and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001).
      The area under the receiver operating characteristic curve of the combination of
      2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI},
      0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI,
      Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared
      with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI
      assays. Reclassification analysis confirmed the superiority of absolute changes
      versus relative changes. CONCLUSIONS: Absolute changes seem to be the preferred
      metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial
      infarction. The combination of absolute and relative changes provides a small
      added value for hs-cTnT, but not for hs-cTnI.

PMID- 23870792
TI  - Genotype/phenotype correlations in complement factor H deficiency arising from
      uniparental isodisomy.
AB  - We report a male infant who presented at 8 months of age with atypical hemolytic
      uremic syndrome (aHUS) responsive to plasma therapy. Investigation showed him to
      have complement factor H (CFH) deficiency associated with a homozygous CFH
      mutation (c.2880delT [p.Phe960fs]). Mutation screening of the child's parents
      revealed that the father was heterozygous for this change but that it was not
      present in his mother. Chromosome 1 uniparental isodisomy of paternal origin was
      confirmed by genotyping chromosome 1 SNPs. CD46 SNP genotyping was undertaken in
      this individual and another patient with CFH deficiency associated with
      chromosome 1 uniparental isodisomy. This showed a homozygous aHUS risk haplotype
      (CD46GGAAC) in the patient with aHUS and a homozygous glomerulonephritis risk
      haplotype (CD46AAGGT) in the patient with endocapillary glomerulonephritis. We
      also showed that FHL-1 (factor H-like protein 1) was present in the patient with
      aHUS and absent in the patient with glomerulonephritis. This study emphasizes
      that modifiers such as CD46 and FHL-1 may determine the kidney phenotype of
      patients who present with homozygous CFH deficiency. 

PMID- 23870793
TI  - Outbreak of Escherichia coli O157:H7 in a child care center in Cook County,
      Illinois, with prolonged shedding and household transmission.
AB  - During the investigation of an outbreak of Escherichia coli O157:H7 in a child
      care center, illness logs were reviewed and parents interviewed to identify
      classroom and household exposures. Costs incurred by the center and the public
      health laboratory were estimated from self-administered questionnaires. We
      conclude that household transmission played a role in this outbreak and estimate
      the cost of investigation and intervention at over $6,000 per case. 

PMID- 23870794
TI  - Reducing health care-associated infections: patients want to be engaged and learn
      about infection prevention.
AB  - BACKGROUND: Multidrug-resistant organisms (MDROs) are common in health care
      associated infection (HAI). The aim of this study was to examine patient's
      willingness to learn about MDROs and HAIs and their preferred ways of education
      about MDRO HAIs. METHODS: Interviewer-administered questionnaire at a tertiary
      care academic medical center. We recruited a sample of 100 adult patients who had
      HAI and were placed in contact precautions. RESULTS: Ninety-six percent of
      patients had heard of MDROs. Ninety-eight percent of patients thought that their
      involvement in learning about MDROs was very important or important. Most of the
      patients thought that receiving information about MDROs would probably or
      definitely help them to make choices that would improve their health care.
      Patients expressed interest in more than 1 form of educational material: 70%
      chose written material, 57% verbal information, 53% an informational video, and
      50% Internet-based material. Patients with a higher level of education were more
      likely to prefer written material. Patients emphasized simple language and
      incorporation of actual patient stories. CONCLUSION: Hospitalized patients with
      MDROs in our study believed that involvement on their part was important.
      Individuals' level of education affected their preference regarding choice of
      educational material, but most patients prefered receiving written or verbal
      information. Patient preferences must be incorporated into education to increase
      engagement for prevention of MDROs and HAIs.

PMID- 23870795
TI  - Antimicrobial activity of copper against organisms in aqueous solution: a case
      for copper-based water pipelines in hospitals?
AB  - BACKGROUND: An association exists between water of poor quality and health care
      associated infections. Copper shows microbiocidal action on dry surfaces; it is
      necessary to evaluate its antimicrobial effect against organisms in aqueous
      solution. OBJECTIVE: The objective was to determine the in vitro antimicrobial
      activity of copper against common nosocomial pathogens in aqueous solution.
      METHODS: Copper and polyvinyl chloride containers were used. Glass was used as
      control material. Fourteen organisms isolated from hospital-acquired infections,
      and 3 control strains were tested. Inocula were prepared by direct suspension of
      colonies in saline solution and water in each container tested. Bacterial counts
      in colony-forming units (CFU)/mL were determined at the beginning of the
      experiment; at 30 minutes; and at 1, 2, 24, and 48 hours. RESULTS: Organisms in
      glass and polyvinyl chloride remained viable until the end of the experiment.
      Organisms in copper showed a reduction from more than 100,000 CFU/mL to 0 CFU/mL
      within the first 2 hours of contact (F > 4.29, P < .001). CONCLUSION: Copper
      containers show microbiocidal action on organisms in aqueous solution. Copper may
      contribute to the quality of water for human use, particularly in hospitals.

PMID- 23870796
TI  - Mitochondrial activity and oxidative stress markers in peripheral blood
      mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy
      subjects.
AB  - Evidence suggests that mitochondrial dysfunction is involved in the
      pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar
      disorder (BD). However, the exact mechanisms underlying this dysfunction are not
      well understood. Impaired activity of electron transport chain (ETC) complexes
      has been described in these disorders and may reflect changes in mitochondrial
      metabolism and oxidative stress markers. The objective of this study was to
      compare ETC complex activity and protein and lipid oxidation markers in 12
      euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in
      30 matched healthy volunteers. Activity of complexes I, II, and III was
      determined by enzyme kinetics of mitochondria isolated from peripheral blood
      mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein
      carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid
      reactive substances (TBARS) assay kit. A significant decrease in complex I
      activity was observed (p = 0.02), as well as an increase in plasma levels of
      TBARS (p = 0.00617) in patients with SZ when compared to matched controls.
      Conversely, no significant differences were found in complex I activity (p =
      0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched
      controls. Our results suggest that mitochondrial complex I dysfunction and
      oxidative stress play important roles in the pathophysiology of SZ and may be
      used in potential novel adjunctive therapy for SZ, focusing primarily on
      cognitive impairment and disorder progression.

PMID- 23870797
TI  - An examination of low distress tolerance and life stressors as factors underlying
      obsessions.
AB  - A growing body of research has linked poor distress tolerance (DT) to obsessions,
      but not other OC symptom domains. However, limited research has been conducted
      with clinical samples. Further, there is a dearth of research regarding the
      moderating influence of DT on the contribution of stress to OC symptoms. In Study
      1, we sought to test the specificity of the link between poor DT and greater
      obsessions relative to other OC symptom domains in a clinical sample. In Study 2,
      we conducted a longitudinal investigation with a non-clinical sample examining DT
      and daily stressors in the prediction of daily obsessions. For Study 1, 22
      outpatients with an OCD diagnosis and 37 healthy controls completed measures of
      DT, depression, and OC symptoms. For Study 2, 102 undergraduates completed
      measures of DT at baseline and daily assessments of OC symptoms and stressors
      twice weekly for one-month. In Study 1, OCD diagnosis was not a significant
      predictor of DT, though greater obsessions, but not other OC symptoms, were
      uniquely associated with lower DT. In Study 2, lower baseline DT predicted
      greater daily obsessions among those experiencing greater daily negative life
      events, though this relationship was absent among those with elevated DT. The
      specific association between DT and obsessions was replicated in a clinical
      sample. Further, results suggest that low DT increases obsessions in the context
      of life stress. 

PMID- 23870799
TI  - The major role of viruses in cellular evolution: facts and hypotheses.
AB  - Viral particles are much more abundant than cells and viral genes outnumber
      cellular ones in the biosphere. Cellular genomes also harbour many integrated
      viruses whereas cellular genes are rare in viral genomes. The gene flux from
      virus to cell is thus overwhelming if compared with the opposite event. Novel
      viral genes continuously arose during replication/recombination of viral genomes
      in the virocell. These genes can become 'cellular genes' when viral genomes
      integrate into cellular ones. Together with the arm race between viruses and
      cells, this explains why viruses have played a major role in shaping cellular
      gene contents. Several documented cases show that viruses have been involved in
      the emergence of evolutionary innovations. This gives credit to hypotheses
      suggesting that viruses have played an important role in the formation of modern
      cells. 

PMID- 23870798
TI  - Add-on memantine to valproate treatment increased HDL-C in bipolar II disorder.
AB  - Memantine is a noncompetitive NMDA receptor antagonist. As an augmenting agent,
      it has an antidepressant-like and mood-stabilizing effect. Memantine also reduces
      binge eating episodes and weight. We investigated whether memantine added on to
      valproate (VPA) is more effective than VPA alone for treating BP-II depression
      and improving the patient's metabolic profile. This was a randomized, double
      blind, controlled study. BP-II patients undergoing regular VPA treatments were
      randomly assigned to one of two groups: VPA plus either add-on [1] memantine (5
      mg/day) (n = 62) or [2] placebo (n = 73) for 12 weeks. The Young Mania Rating
      Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate
      clinical response. Height, weight, fasting serum glucose, fasting total
      cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C), and triglycerides were followed regularly.
      Multiple linear regressions with generalized estimating equation methods were
      used to analyze the effects of memantine on clinical performance. There were no
      significant differences in pre- and post-treatment YMRS and HDRS scores between
      the VPA + memantine and VPA + placebo groups. Although there were no significant
      differences in the pre- and post-treatment values of most metabolic indices
      between the two groups, there was a significant increase of HDL-C (p = 0.009) in
      the VPA + memantine group compared with the VPA + placebo group. This increase
      remained significant even after controlling for body mass index (BMI) (p =
      0.020). We conclude that add-on memantine plus VPA treatment of BP-II depression
      increases the blood level of HDL-C even in the absence of change in affective
      symptoms. TRIAL REGISTRATION: NCT01188148 (https://register.clinicaltrials.gov/),
      Trial date was from 1st August, 2008 to 31st July, 2012 in National Cheng Kung
      University and Tri-Service General Hospital.

PMID- 23870800
TI  - Suprachoroidal hemorrhage in pars plana vitrectomy: risk factors and outcomes
      over 10 years.
AB  - PURPOSE: To investigate the rate and risk factors of developing suprachoroidal
      hemorrhage (SCH) after pars plana vitrectomy (PPV) and the outcomes as a result.
      DESIGN: Retrospective, comparative consecutive series. PARTICIPANTS: A total of
      5459 patients who underwent pars plana vitrectomies over 10 years in 3 surgical
      centers. METHODS: All patient demographic, medical, and ophthalmic data and
      operative information from 3 vitreoretinal centers were entered prospectively
      into an electronic medical record. Univariate analysis was undertaken, comparing
      risk factors between cases (SCH) and controls. Multivariable logistic regression
      was performed to test for independence between the risk factors (P < 0.2 in
      univariate analysis) and SCH. MAIN OUTCOME MEASURES: Risk factors for developing
      SCH. Visual outcome and development of complications. RESULTS: A total of 5459
      PPVs were undertaken for a wide range of indications. Fifty-six cases of PPV were
      complicated by SCH (1.03%). Multivariable logistic regression showed that
      significant risk factors for developing this included advancing age, (mean age,
      69 years in cases and 60 years in controls; odds ratio [OR], 1.04; P = 0.001),
      male sex (76.8% of cases and 58.7% of controls; OR, 2.38; P = 0.008), presence of
      rhegmatogenous retinal detachment (RRD) (80.3% of cases and 52.5% of controls;
      OR, 5.92; P < 0.0001), presence of a dropped lens fragment (10.7% of cases and
      4.5% of controls; OR, 6.94; P = 0.002), and the use of antiplatelet or
      anticoagulant drugs (33.9% of cases and 17.7% of controls; OR, 2.29; P = 0.007).
      Suprachoroidal hemorrhage was more common with increasing quadrants of RRD. The
      significant operative risk factor was application of an explant (25% of cases and
      4.07% of controls; OR, 5.63; P < 0.0001). Phthisis (7.1% of cases and 0.9% of
      controls; P = 0.002, Fisher exact test) and glaucoma (14.3% of cases and 7.2% of
      controls; P = 0.044, chi-square test) were more common in cases than in controls.
      CONCLUSIONS: The risk factors for developing intraoperative SCH during PPV are
      male sex, advancing age, RRD, a scleral explant, a dropped lens fragment, and the
      use of aspirin or warfarin. Patients with this complication have a greater risk
      of developing ocular hypertension requiring treatment and phthisis.

PMID- 23870802
TI  - Human intestinal metagenomics: state of the art and future.
AB  - Over the last few years our understanding of human biology has undergone profound
      transformation. The key role of the 'world inside us', namely the gut microbiota,
      once considered a forgotten organ, has been revealed, with strong impact on our
      health and well-being. The present review highlights the most important recent
      findings on the role of gut microbiota and its impact on the host and raises
      crucial questions to be considered in future studies. 

PMID- 23870803
TI  - Reproductive hormone monitoring of dugongs in captivity: detecting the onset of
      sexual maturity in a cryptic marine mammal.
AB  - Determining the reproductive status of long-term captive animals is essential
      because the onset of sexual maturity and reproductive activity may necessitate
      changes in husbandry requirements. This study reports on the first multi-year
      reproductive hormone monitoring program for captive dugongs of both sexes using
      feces. Fecal samples were collected from one male (Pig) over 9 years (4-13.2y of
      age; n=288 samples, 0.8+/-0.1 samples per week from July 2007 to February 2012)
      and one female (Wuru) over 7 years (from neonate to 6.9 y; n=171 samples, 0.5+/
      0.1 samples per week from July 2007 to February 2012), and from one solitary
      female dugong (Gracie) over 10 months (10.5-11.3y of age; n=54 samples, 1.1+/-0.2
      sample per week from September 2008 to June 2009). Using enzyme-immunoassay,
      fecal progesterone (fP) and estradiol-17beta (fE) concentrations were assayed in
      the two captive females, and testosterone (fT) concentration in the captive male,
      and compared these to concentrations in wild dugongs. Female Wuru exhibited
      increasing fP concentrations at 5+ y, indicating early onset of ovarian cycling
      typical of non-pregnant adult females. Female Gracie maintained basal fP
      concentrations consistent with wild immature dugongs, indicating that she had not
      reached puberty by 11y. Nutritional plane may account for differences in age at
      sexual maturity in these female dugongs. At age 3-4y, Wuru had fE concentrations
      1.4 times greater than maximum concentrations recorded in all wild females, and
      these concentrations were coincident with a period of rapid weight gain. For the
      male Pig, increasing fT concentrations at 9y provided early indications of
      puberty. Pig's tusks erupted by 11y, and sexual maturity (indicated by spermatic
      semen) was confirmed by 12.8y. Identification of sexual maturation prompted two
      trials of a male contraceptive treatment using the GnRH agonist, deslorelin
      (9.4mg administered in 2010 and 15.6mg in 2011). Testosterone production was not
      significantly suppressed by these dosages, and treatment did not terminate sperm
      production at week 10-11 post-implantation, even at the larger dose tested.
      Routine analysis of fecal hormones was helpful for making reproductive management
      decisions regarding individual captives and in guiding the long-term captive
      management of this cryptic species. 

PMID- 23870804
TI  - Development of in vitro assays for measuring the relative potency of leptospiral
      bacterins containing serogroups canicola, grippotyphosa, icterohaemorrhagiae, and
      pomona.
AB  - Historically, potency testing of bacterins containing Leptospira involved a
      hamster vaccination-challenge assay. The United States Department of Agriculture
      (USDA) has long recognized that an in vitro system has several inherent
      advantages over the animal model. This is a review of the work performed at the
      USDA to replace the hamster vaccination-challenge model used to test Leptospira
      bacterins. The work covered a span of approximately 20 years and resulted in the
      development of USDA monoclonal antibody based enzyme-linked immunosorbent assays
      (ELISAs) for the quantitation of antigen in bacterins containing Leptospira
      serogroups canicola, icterohaemorrhagiae, pomona, and grippotyphosa. The
      monoclonal antibodies used in the assay a) recognize lipopolysaccharide-like
      epitopes on the surface of the whole cell, b) agglutinate the homologous
      leptospiral serovars but do not agglutinate heterologous leptospiral serovars or
      heterologous bacterial species, and c) passively protect hamsters against a
      homologous challenge but fail to protect hamsters against heterologous
      challenges. Once developed, the performance of each ELISA was evaluated at the
      USDA followed by industry evaluation. Serials that passed the hamster vaccination
      challenge assay yielded ELISA relative potency values of 1.0 or greater. These
      ELISAs have been shown to be a reproducible, sensitive, specific, and inexpensive
      alternative to the current Codified hamster potency assay.

PMID- 23870805
TI  - Adenosine hypothesis in schizophrenia and bipolar disorder: a systematic review
      and meta-analysis of randomized controlled trial of adjuvant purinergic
      modulators.
AB  - OBJECTIVE: Adenosine has been reported to interact with dopamine and glutamate of
      which are currently central pathophysiology of schizophrenia. Further, there have
      been emerging reports that patients with bipolar disorder (BD) have
      pathophysiological changes of the purinergic system. Thus, we performed a
      systematic review and meta-analysis of adenosine modulators in these disorders.
      METHOD: We searched PubMed, EMBASE, the Cochrane Library databases, CINAHL, and
      PsycINFO up to April 25, 2013. Randomized controlled trials comparing adenosine
      modulator adjuvant therapy with placebo in patients with schizophrenia and BD
      were included. Primary outcome measures were Positive and Negative Syndrome Scale
      (PANSS) and Young Mania Rating Scales (YMRS). The risk ratio, 95% confidence
      interval, and standardized mean differences (SMD) were used. RESULTS: Nine
      studies, including six studies in schizophrenia (total n=457) and three studies
      in BD (total n=289) were included. Overall, adenosine modulators were superior to
      placebo in PANSS total scores (SMD=-1.07, p=0.01) and positive and general but
      not negative symptom subscale scores in schizophrenia. Individually, allopurinol
      failed to show its superiority to placebo in all primary outcome measures in
      schizophrenia. In BD, data from pooled adenosine modulators indicated significant
      reduction of YMRS scores in comparison to placebo (SMD=-0.39, p=0.004).
      CONCLUSIONS: Our results suggest that adenosine modulator adjuvant therapy is
      more beneficial in overall psychopathology (especially positive symptoms) in
      schizophrenia and in treating mania episodes of BD in comparison to placebo. The
      limited sample size of available studies suggests that more research should be
      done to evaluate both efficacy and tolerability of these medications.

PMID- 23870806
TI  - Preventing a first episode of psychosis: meta-analysis of randomized controlled
      prevention trials of 12 month and longer-term follow-ups.
AB  - Over the last decade many studies were conducted to assess the feasibility of
      early detection of people at risk of developing psychosis and intervention to
      prevent or delay a first psychotic episode. Most of these studies were small and
      underpowered. A meta-analysis can demonstrate the effectiveness of the efforts to
      prevent or postpone a first episode of psychosis. A search conducted according
      the PRISMA guideline identified 10 studies reporting 12-month follow-up data on
      transition to psychosis, and 5 studies with follow-ups varying from 24 to 48
      months. Both random and fixed effects meta-analyses were conducted. The quality
      of the studies varied from poor to excellent. Overall the risk reduction at 12
      months was 54% (RR=0.463; 95% CI=0.33-0.64) with a Number Needed to Treat (NNT)
      of 9 (95% CI=6-15). Although the interventions differed, there was only mild
      heterogeneity and publication bias was small. All sub-analyses demonstrated
      effectiveness. Also 24 to 48-month follow-ups were associated with a risk
      reduction of 37% (RR=.635; 95% CI=0.44-0.92) and a NNT of 12 (95% CI=7-59).
      Sensitivity analysis excluding the methodologically weakest study showed that the
      findings were robust. Early detection and intervention in people at ultra-high
      risk of developing psychosis can be successful to prevent or delay a first
      psychosis. Antipsychotic medication showed efficacy, but more trials are needed.
      Omega-3 fatty acid needs replication. Integrated psychological interventions need
      replication with more methodologically sound studies. The findings regarding CBT
      appear robust, but the 95% confidence interval is still wide.

PMID- 23870807
TI  - Randomized trial of clozapine vs. risperidone in treatment-naive first-episode
      schizophrenia: results after one year.
AB  - In first-episode patients with psychosis, clozapine may be potentially valuable
      as an initial treatment seeking to limit early on clinical and cognitive
      deterioration. Nevertheless, until recently its restricted use has limited the
      study of this possibility. Our research group is developing a non-commercial,
      multicentric and open label study on the differential efficacy between clozapine
      and risperidone in first-episode schizophrenia. In this paper, we present the
      results related to clinical variables after a one-year follow-up. So far, we have
      recruited 30 patients diagnosed with schizophrenia or schizophreniform disorder
      with illness duration of less than two years. The patients had not received any
      previous treatment and they were randomized to treatment with clozapine or
      risperidone. Our results indicate that on average, patients on clozapine adhered
      to their original treatment for a longer time period than patients on
      risperidone. By last observation carried forward (LOCF) analysis, patients on
      clozapine and risperidone displayed similar clinical improvements, although
      marginally greater improvements in positive and total symptoms scores were found
      in the clozapine group. At the 12-month point we observed a marginal improvement
      in negative symptom scores in patients on clozapine. Subjective secondary
      effects, as measured with the Udvalg for KliniskeUndersogelser (UKU) scale,
      correlated negatively with negative symptoms at follow-up. Our data, although
      preliminary, suggest that clozapine may have a slightly superior efficacy in the
      initial year of treatment of first-episode treatment-naive patients with
      schizophrenia, and this can be explained for the most part by greater adherence
      to this treatment. 

PMID- 23870808
TI  - CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the
      evidence.
AB  - Although a number of first- and second-generation antipsychotics are available,
      achieving optimal therapeutic response for patients with schizophrenia can be
      challenging. The presence of polymorphic alleles for cytochrome P (CYP) 450 may
      result in lack of expression, altered levels of expression, or altered function
      of CYP450 enzymes. CYP2D6, CYP1A2, and CYP3A4/5 are major enzymes in the
      metabolism of antipsychotics and polymorphisms of alleles for these proteins are
      associated with altered plasma levels. Consequently, standard dosing may result
      in drug plasma concentrations that are subtherapeutic or toxic in some patients.
      Patient CYP450 genotype testing can predict altered pharmacokinetics, and is
      currently available and relatively inexpensive. Evidence-based guidelines provide
      dose recommendations for some antipsychotics. To date few studies have
      demonstrated a significant association with genotype-guided antipsychotic use and
      clinical efficacy. However, many studies have been small, retrospective or cohort
      designs, and many have not been adequately powered. Numerous studies have shown a
      significant association between genotype and adverse effects, such as CYP2D6
      polymorphisms and tardive dyskinesia. This review summarizes evidence for the
      role of CYP450 genetic variants in the response to antipsychotic medications and
      the clinical implications of pharmacogenetics in the management of patients with
      schizophrenia. 

PMID- 23870809
TI  - Fearful face recognition in schizophrenia: an electrophysiological study.
AB  - BACKGROUND: Emotional expressions are important acts of communication, and
      impairment in facial emotion recognition has been shown to be related to
      impairments in social cognition in schizophrenia. We used an event-related
      potential (ERP) paradigm to identify and delineate the temporal characteristics
      in the electrophysiological cascade related to fearful facial affect processing
      in patients with schizophrenia as compared to healthy controls. METHODS: Twenty
      four subjects with schizophrenia and 24 individually matched healthy controls
      participated in an emotion recognition task. Ekman faces displaying neutral and
      fearful facial expressions were used as stimuli. ERPs were recorded using a 128
      channel EEG system. RESULTS: Based on the analysis of Global Field Power (GFP) in
      the 150-190 ms time window both groups differentiated between fearful and neutral
      faces. Schizophrenia patients showed an additional differential processing of
      fearful vs. neutral faces in the 330-450 ms time window, and this ERP effect
      correlated with psychopathology. CONCLUSIONS: Both patients and healthy controls
      differentiate fearful and neutral faces in early phases of emotion processing.
      Our results also indicate that schizophrenia patients show increased responsivity
      to fearful faces at a later processing stage. This could be related to the
      overrating of negative emotions, and the symptomatology associated with fear
      processing in patients with schizophrenia.

PMID- 23870810
TI  - Context and the perception of emotion in schizophrenia: sex differences and
      relationships with functioning.

PMID- 23870811
TI  - D-cycloserine enhancement of exposure therapy for social anxiety disorder depends
      on the success of exposure sessions.
AB  - OBJECTIVE: The evidence for the efficacy of D-cycloserine (DCS) for augmenting
      cognitive behavioral therapy (CBT) for anxiety disorders has been mixed. Guided
      by preclinical research and initial findings from a small-scale study involving
      humans, we tested the hypothesis that DCS enhancement of exposure therapy would
      be specific to successful exposure sessions. METHOD: Medication-free adults with
      generalized social anxiety disorder (N = 145) received 50 mg of DCS or placebo 1
      h before each of 5 exposure sessions that were part of a standardized 12-session
      group CBT protocol. Participants provided fear ratings at the beginning and just
      before the end of exposure exercises. Independent raters, blind to group
      assignment, administered the clinical global impression improvement and severity
      scales at each session and at posttreatment. RESULTS: Mixed-effects analyses
      revealed that, among patients who reported low fear at the end of an exposure
      session, those who had received DCS evidenced significantly greater clinical
      improvement at the next session, relative to those who had received placebo. In
      contrast, when exposure end fear was high, patients receiving DCS exhibited less
      clinical improvement at the following session than patients receiving placebo.
      Similarly, patients who had received DCS evidenced lower clinical severity at
      posttreatment, relative to patients who had received placebo, only when their
      average end fear for medication-augmented sessions had been in the low to
      moderate range. Finally, these moderating effects of exposure success as indexed
      by end fear were not better accounted for by within-session extinction.
      CONCLUSIONS: The efficacy of DCS for augmenting exposure-based CBT depends on the
      success of exposure sessions. These findings may help guide the development of an
      algorithm for the effective use of DCS for augmenting exposure-based CBT. TRIAL
      REGISTRY: http://www.ClinicalTrials.gov, ID# NCT00633984,
      http://www.clinicaltrials.gov/ct2/show/NCT00633984.

PMID- 23870812
TI  - Treatment of age-related macular degeneration.

PMID- 23870814
TI  - The demise of calcium-based phosphate binders.

PMID- 23870813
TI  - Alternative treatments to inhibit VEGF in age-related choroidal
      neovascularisation: 2-year findings of the IVAN randomised controlled trial.
AB  - BACKGROUND: Bevacizumab has been suggested to have similar effectiveness to
      ranibizumab for treatment of neovascular age-related macular degeneration. The
      Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial was
      designed to compare these drugs and different regimens. Here, we report the
      findings at the prespecified 2-year timepoint. METHODS: In a multicentre, 2*2
      factorial, non-inferiority randomised trial, we enrolled adults aged at least 50
      years with active, previously untreated neovascular age-related macular
      degeneration and a best corrected distance visual acuity (BCVA) of at least 25
      letters from 23 hospitals in the UK. Participants were randomly assigned
      (1:1:1:1) to intravitreal injections of ranibizumab (0.5 mg) or bevacizumab (1.25
      mg) in continuous (every month) or discontinuous (as needed) regimens, with
      monthly review. Study participants and clinical assessors were masked to drug
      allocation. Allocation to continuous or discontinuous treatment was masked up to
      3 months, at which point investigators and participants were unmasked. The
      primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of
      3.5 letters. The primary safety outcome was arterial thrombotic event or hospital
      admission for heart failure. Analyses were by modified intention to treat. This
      trial is registered, number ISRCTN92166560. FINDINGS: Between March 27, 2008, and
      Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610
      received study drugs (314 ranibizumab; 296 bevacizumab) and were included in
      analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in
      continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in
      continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA,
      bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference
      -1.37 letters, 95% CI -3.75 to 1.01; p=0.26). Discontinuous treatment was neither
      non-inferior nor inferior to continuous treatment (-1.63 letters, -4.01 to 0.75;
      p=0.18). Frequency of arterial thrombotic events or hospital admission for heart
      failure did not differ between groups given ranibizumab (20 [6%] of 314
      participants) and bevacizumab (12 [4%] of 296; odds ratio [OR] 1.69, 95% CI 0.80
      3.57; p=0.16), or those given continuous (12 [4%] of 308) and discontinuous
      treatment (20 [7%] of 302; 0.56, 0.27-1.19; p=0.13). Mortality was lower with
      continuous than discontinuous treatment (OR 0.47, 95% CI 0.22-1.03; p=0.05), but
      did not differ by drug group (0.96, 0.46-2.02; p=0.91). INTERPRETATION:
      Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of
      retreatment resulted in a small loss of efficacy irrespective of drug. Safety was
      worse when treatment was administered discontinuously. These findings highlight
      that the choice of anti-VEGF treatment strategy is less straightforward than
      previously thought. FUNDING: UK National Institute for Health Research Health
      Technology Assessment programme.

PMID- 23870815
TI  - Nodular lymphoid hyperplasia in common variable immunodeficiency.

PMID- 23870816
TI  - Syrian refugees in Lebanon: facts and solutions.

PMID- 23870817
TI  - Effect of calcium-based versus non-calcium-based phosphate binders on mortality
      in patients with chronic kidney disease: an updated systematic review and meta
      analysis.
AB  - BACKGROUND: Phosphate binders (calcium-based and calcium-free) are recommended to
      lower serum phosphate and prevent hyperphosphataemia in patients with chronic
      kidney disease, but their effects on mortality and cardiovascular outcomes are
      unknown. We aimed to update our meta-analysis on the effect of calcium-based
      versus non-calcium-based phosphate binders on mortality in patients with chronic
      kidney disease. METHODS: We did a systematic review of articles published in any
      language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase,
      International Pharmaceutical Abstracts, Cochrane Central Register of Controlled
      Trials, and Cumulative Index to Nursing and Allied Health Literature. We included
      all randomised and non-randomised trials that compared outcomes between patients
      with chronic kidney disease taking calcium-based phosphate binders with those
      taking non-calcium-based binders. Eligible studies, determined by consensus with
      predefined criteria, were reviewed, and data were extracted onto a standard form.
      We combined data from randomised trials to assess the primary outcome of all
      cause mortality using the DerSimonian and Laird random effects model. FINDINGS:
      Our search identified 847 reports, of which eight new studies (five randomised
      trials) met our inclusion criteria and were added to the ten (nine randomised
      trials) included in our previous meta-analysis. Analysis of the 11 randomised
      trials (4622 patients) that reported an outcome of mortality showed that patients
      assigned to non-calcium-based binders had a 22% reduction in all-cause mortality
      compared with those assigned to calcium-based phosphate binders (risk ratio 0.78,
      95% CI 0.61-0.98). INTERPRETATION: Non-calcium-based phosphate binders are
      associated with a decreased risk of all-cause mortality compared with calcium
      based phosphate binders in patients with chronic kidney disease. Further studies
      are needed to identify causes of mortality and to assess whether mortality
      differs by type of non-calcium-based phosphate binder. FUNDING: None.

PMID- 23870818
TI  - Main histologic types of non-small-cell lung cancer differ in expression of
      prognosis-related genes.
AB  - BACKGROUND: There is increasing evidence that suggests that particular
      histopathologic types of non-small-cell lung cancer (NSCLC) display distinct
      molecular characteristics. We analyzed, in lung squamous cell carcinoma (SCC) and
      adenocarcinoma (AC), the expression of 8 genes that constitute 2 previously
      reported prognostic expression signatures in NSCLC. METHODS: Fresh-frozen tumor
      and normal lung samples were obtained at surgery from 135 patients with stage I
      III NSCLC (89 (65.9%) SCC, 46 (34.1%) AC). Expression of CSF1 (colony stimulating
      factor for macrophages), carbonic anhydrase 9 (CA9), epithelial growth factor
      receptor (EGFR), dual specificity phosphatase 6 (DUSP6), v-erb-b2 erythroblastic
      leukemia viral oncogene homolog 3 (ERBB3), monocyte to macrophage differentiation
      associated (MMD), lymphocyte-specific protein tyrosine kinase (LCK) and signal
      transducer and activator of transcription 1 (STAT1) was assessed in SCC, AC, and
      in normal lung by quantitative reverse transcriptase - polymerase chain reaction
      (qRT-PCR). Metastasis-free survival was analyzed according to the median value of
      gene expression in the entire NSCLC cohort and separately in SCC and AC. RESULTS:
      Expression of CA9, CSF1, DUSP6, STAT1, and MMD differed between NSCLC and normal
      lung. EGFR was more abundant in SCC compared with AC, whereas the reverse was
      true for DUSP6 and ERBB3. A high expression of CSF1 correlated with shorter
      metastasis-free survival in the entire NSCLC group (P = .016) and in SCC (P =
      .049) and AC (P = .034) cohorts. CONCLUSIONS: Several genes considered prognostic
      in NSCLC showed significantly different expression in SCC and AC, and thus should
      be analyzed separately in these 2 subtypes for their prognostic significance.
      CSF1 is similarly expressed in SCC and AC, and portends a poor outcome in the
      entire group of patients with NSCLC, and in SCC and AC when considered
      separately.

PMID- 23870819
TI  - The influence of ferrule effect and length of cast and FRC posts on the stresses
      in anterior teeth.
AB  - OBJECTIVES: The purpose was to assess the influence of ferrule effect and length
      of cast post and cores, and FRC posts on the strength of anterior teeth.
      MATERIALS AND METHODS: The investigations were conducted by means of finite
      element analysis with the application of contact elements. Thirteen 3D models of
      maxillary first incisors were generated: model 1 was an intact tooth; 2A - a
      tooth with all-ceramic crown with ferrule effect, 2B-D a teeth restored with,
      ferrule and FRC posts of various lengths 13mm, 8mm, 4mm, 3A - a tooth with
      ceramic crown without, ferrule effect, 3B and C teeth without ferrule and 10mm,
      5mm length FRC posts, 4B-D teeth with ferrule, restored by cast posts and cores
      of 13mm, 8mm, 4mm lengths and 5B and C teeth without ferrule, restored with cast
      posts and cores of 10mm, 5mm lengths. Each model was subject to a load with a
      total force of 100N uniformly distributed under the lingual cingulum, at an angle
      of 130 degrees . To evaluate, the strength of tooth tissues, ceramics and
      composites, the modified von Mises failure criterion was used, for FRC the Tsai
      Wu criterion and for cast NiCr alloy the von Mises criterion. Contact stresses
      were calculated at the luting cement-tissue interface. RESULTS: Ferrule effect in
      teeth reduces mvM stresses in dentin, in posts and in luting cement. The contact
      tensile stresses around posts in teeth with ferrule effect were 1.7-3.0 times
      smaller than in, teeth without ferrule. Lower mvM stresses occurred in teeth with
      cast posts in comparison with FRC posts. The mvM stresses in teeth with posts of
      various lengths were similar, irrespective of post material. SIGNIFICANCE:
      Ferrule effect in teeth with posts and cores has a critical influence on stress
      reduction. Using posts and cores made of rigid materials leads to stress
      reduction in teeth. Post length has a small, effect on stress values in tooth
      structures.

PMID- 23870820
TI  - Paroxysmal gaze deviations as the sole manifestation of occipital lobe epilepsy.

PMID- 23870821
TI  - Bioactive metabolites from an endophytic Cryptosporiopsis sp. inhabiting Clidemia
      hirta.
AB  - An endophytic Cryptosporiopsis sp. was isolated from Clidemia hirta and analyzed
      for its secondary metabolites that lead to the isolation of three bioactive
      molecules. The compounds were purified from the culture broth of the fungus and
      their structures were determined by spectroscopic methods as (R)-5-hydroxy-2
      methylchroman-4-one (1), 1-(2,6-dihydroxyphenyl)pentan-1-one (2) and (Z)-1-(2-(2
      butyryl-3-hydroxyphenoxy)-6-hydroxyphenyl)-3-hydroxybut-2-en-1-one (3). Compound
      1 exhibited significant cytotoxic activity against the human leukemia cell line,
      HL-60 with an IC50 of 4 MUg/ml. This compound induced G2 arrest of the HL-60 cell
      cycle significantly. In addition, out of these compounds, 2 and 3 were active
      against several bacterial pathogens. Compound 2 was active against Bacillus
      cereus, Escherichia coli and Staphylococcus aureus with IC50 values varying from
      18 to 30 MUg/ml, and compound 3 displayed activity against Pseudomonas
      fluorescens with an IC50 value of 6 MUg/ml. Compounds 2 and 3 are novel whereas
      compound 1 was reported earlier but the stereochemistry of its C-2 methyl is
      established for the first time.

PMID- 23870822
TI  - Hematoma of the labia minora following consensual sexual intercourse.

PMID- 23870823
TI  - Decidual cast after discontinuation of oral contraceptives use in a young girl.
AB  - BACKGROUND: The differential diagnosis of tissue passed per vagina in a young
      girl includes aborted pregnancy, rhabdomyosarcoma, polyp, and very rarely
      decidual cast. CASE: A 10-year-old girl using oral contraceptives for menorrhagia
      presented with a decidual cast after discontinuing the drug. Symptoms disappeared
      during clinical follow-up without any intervention. CONCLUSIONS: Decidual cast
      formation is an unusual entity of unknown origin. It's generally seen during
      treatment with variable contraceptives. This is the first case described with
      desogestrel and it occurred after discontinuing treatment.

PMID- 23870824
TI  - Monocyte-derived dendritic cell subpopulations use different types of matrix
      metalloproteinases inhibited by GM6001.
AB  - Matrix metalloproteinases (MMPs) are endopeptidases with the potential to cleave
      extracellular matrix, support tissue renewal and regulate cell migration.
      Functional activities of MMPs are regulated by tissue inhibitors of MMPs (TIMPs)
      and disruption of the MMP-TIMP balance has pathological consequences. Here we
      studied the expression and secretion of MMPs and TIMPs in CD1a(-) and CD1a(+)
      monocyte-derived dendritic cell (DC) subpopulations. Our results showed that
      monocytes express TIMPs but lack MMPs, whereas upon differentiation to moDCs and
      in response to activation signals the expression of MMPs is increased and that of
      TIMPs is decreased. MMP-9 is expressed dominantly in the CD1a(-) subpopulation,
      while MMP-12 is preferentially expressed in CD1a(+) cells. Experiments performed
      with the synthetic MMP inhibitor GM6001 revealed that this drug efficiently
      inhibits the migration of moDCs through inactivation of MMPs. We conclude that
      modulation of MMP activity by GM6001 emerges as a novel approach to manipulate DC
      migration under inflammatory conditions. 

PMID- 23870825
TI  - Pro-inflammatory cytokines negatively regulate PPARgamma mediated gene expression
      in both human and murine macrophages via multiple mechanisms.
AB  - PPARgamma is a lipid activated transcription factor that connects lipid
      metabolism and immune function. It is known that anti-inflammatory cytokines,
      such as IL-4 that mediates the differentiation of alternatively activated
      macrophages, positively modulate PPARgamma at three levels: by (1) increasing its
      expression (2), initiating a complex formation with STAT6 enhances its
      transcriptional activity and (3) increasing endogenous ligand production. On the
      other hand, PPARgamma is known to inhibit inflammatory processes via
      transrepression. However, the impact of a pro-inflammatory cytokine milieu on
      PPARgamma transcriptional activity in macrophages is less understood. We
      hypothesized that pro-inflammatory cytokines, such as IFNgamma and TNFalpha
      negatively regulate PPARgamma activity and sought to test this within human and
      murine macrophage models using both global and single target gene expression
      analysis. We found that IFNgamma/TNFalpha inhibited PPARgamma expression in human
      CD14+ monocytes derived macrophages and mouse bone marrow derived macrophages,
      but not in macrophages originating from CD34+ stem cells or Thp-1 monocytic
      cells. Irrespective of the model system, the ability of PPARgamma to regulate
      gene expression was inhibited. Moreover, we demonstrated that in Thp-1 cells
      PPARgamma in vitro DNA binding remained unchanged following IFNgamma/TNFalpha pre
      treatment. Taken together, our data suggest that pro-inflammatory conditions
      inhibit PPARgamma activity at the gene expression level and propose two, mutually
      not exclusive models as mechanisms: (1) the level of PPARgamma itself is down
      regulated by the cytokines leading to loss of function, while (2) PPARgamma
      itself remains associated with the DNA though unable to initiate gene expression.
      These findings support that inflammatory conditions skew the lipid sensing
      function of macrophages, further contributing to the vicious circle of metabolic
      disorders. 

PMID- 23870826
TI  - Immunomodulatory approaches for prevention and treatment of infectious diseases.
AB  - With increasing pathogen resistance to antibiotics, population ageing, and threat
      of pandemics there is a strong interest in the development of new approaches for
      the treatment of infectious diseases. Immunomodulatory therapies are defined as
      interventions that target the host rather than the pathogen, modulating the
      immune response with the aim of disease prevention or treatment. Our growing
      understanding of the immune system continues to offer novel drug targets and
      approaches for immunomodulatory interventions. In this review we will cover
      prominent examples of immunomodulatory therapies already in clinical use, as well
      as the recent advances in the development of new immunomodulators in ongoing
      clinical trials. 

PMID- 23870828
TI  - Twenty-year analysis of autologous support of the pulmonary autograft in the Ross
      procedure.
AB  - BACKGROUND: The Ross procedure is seldom offered to adults less than 60 years of
      age who require aortic valve replacement except in a few high-volume centers with
      documented expertise. Inserting the pulmonary autograft as an unsupported root
      replacement may lead to increasing reoperations on the aortic valve in the second
      decade. METHODS: Of 333 patients undergoing the Ross procedure between October
      1992 and June 2012, the study group of 310 consecutive patients (mean age +/-
      standard deviation, 39.3+/-12.7 years (limits 16-63) had the aortic root size
      adjusted to match the pulmonary autograft, which was inserted as a root
      replacement, with the aorta closed up around it to provide autologous support.
      RESULTS: The mean follow-up time was 9.4 years; the actuarial survival was 97% at
      16 years; and freedom from the composite of all reoperations on the aortic valve
      and late echocardiographic-detected aortic regurgitation greater than mild was
      95% at 5 years, 94% at 10 years, and 93% at 15 years. Overall freedom from all
      reoperations on aortic and pulmonary valves was 97% at 5 years, 94% at 10 years,
      and 93% at 15 years. All results were better for the patients presenting with
      predominant aortic stenosis (98% freedom at 15 years) than for those with aortic
      regurgitation (p=0.01). CONCLUSIONS: Autologous support of the pulmonary
      autograft leads to excellent results in the groups presenting with aortic
      stenosis and mixed aortic stenosis/regurgitation and to good results for those
      presenting with pure aortic regurgitation. The Ross procedure, using one of the
      proven, durable techniques available, should be considered for more widespread
      adoption.

PMID- 23870827
TI  - Decellularization of human and porcine lung tissues for pulmonary tissue
      engineering.
AB  - BACKGROUND: The only definitive treatment for end-stage organ failure is
      orthotopic transplantation. Lung extracellular matrix (LECM) holds great
      potential as a scaffold for lung tissue engineering because it retains the
      complex architecture, biomechanics, and topologic specificity of the lung.
      Decellularization of human lungs rejected from transplantation could provide
      "ideal" biologic scaffolds for lung tissue engineering, but the availability of
      such lungs remains limited. The present study was designed to determine whether
      porcine lung could serve as a suitable substitute for human lung to study tissue
      engineering therapies. METHODS: Human and porcine lungs were procured, sliced
      into sheets, and decellularized by three different methods. Compositional,
      ultrastructural, and biomechanical changes to the LECM were characterized. The
      suitability of LECM for cellular repopulation was evaluated by assessing the
      viability, growth, and metabolic activity of human lung fibroblasts, human small
      airway epithelial cells, and human adipose-derived mesenchymal stem cells over a
      period of 7 days. RESULTS: Decellularization with 3-[(3
      Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) showed the best
      maintenance of both human and porcine LECM, with similar retention of LECM
      proteins except for elastin. Human and porcine LECM supported the cultivation of
      pulmonary cells in a similar way, except that the human LECM was stiffer and
      resulted in higher metabolic activity of the cells than porcine LECM.
      CONCLUSIONS: Porcine lungs can be decellularized with CHAPS to produce LECM
      scaffolds with properties resembling those of human lungs, for pulmonary tissue
      engineering. We propose that porcine LECM can be an excellent screening platform
      for the envisioned human tissue engineering applications of decellularized lungs.

PMID- 23870830
TI  - Associations of visceral fat, physical activity and muscle strength with the
      metabolic syndrome.
AB  - OBJECTIVE: We investigated the association of visceral fat with the metabolic
      syndrome (MetS) and its separate components; the associations of both physical
      activity and muscle strength with the MetS and its separate components
      independent of visceral fat. Furthermore, we studied these associations within
      participants with low and high amounts of visceral fat. STUDY DESIGN: 400 men
      (aged 40-80 years) were recruited into a cross-sectional study. MAIN OUTCOME
      MEASURES: Logistic regression models were used to study the individual
      associations in all participants (OR). The associations of physical activity
      (active vs inactive) and muscle strength (high vs low) within participants with
      low and high levels of visceral fat (assessed by ultrasonography) were tested
      using Univariate Analysis of Variance (difference in mean levels of the separate
      components of MetS) and logistic regression (risk on MetS). RESULTS: High levels
      of visceral fat were significantly associated with increased risk of MetS (OR 1.7
      95%CI 1.5;1.9) and its separate components (p<0.05). We did not find strong
      individual associations for physical activity or muscle strength, neither within
      men with low or high levels of visceral fat. CONCLUSIONS: High body fat levels
      were associated with an unhealthier metabolic risk profile and a higher risk of
      the MetS. Our cross-sectional data do not indicate associations for physical
      activity or for muscle strength with the MetS independent of visceral fat. Also
      no differential associations of physical activity or muscle strength in men with
      low or high levels of visceral fat were found.

PMID- 23870829
TI  - A comparative analysis of bronchial stricture after lung transplantation in
      recipients with and without early acute rejection.
AB  - BACKGROUND: Risk factors and outcomes of bronchial stricture after lung
      transplantation are not well defined. An association between acute rejection and
      development of stricture has been suggested in small case series. We evaluated
      this relationship using a large national registry. METHODS: All lung
      transplantations between April 1994 and December 2008 per the United Network for
      Organ Sharing (UNOS) database were analyzed. Generalized linear models were used
      to determine the association between early rejection and development of stricture
      after adjusting for potential confounders. The association of stricture with
      postoperative lung function and overall survival was also evaluated. RESULTS:
      Nine thousand three hundred thirty-five patients were included for analysis. The
      incidence of stricture was 11.5% (1,077/9,335), with no significant change in
      incidence during the study period (P=0.13). Early rejection was associated with a
      significantly greater incidence of stricture (adjusted odds ratio [AOR], 1.40;
      95% confidence interval [CI], 1.22-1.61; p<0.0001). Male sex, restrictive lung
      disease, and pretransplantation requirement for hospitalization were also
      associated with stricture. Those who experienced stricture had a lower
      postoperative peak percent predicted forced expiratory volume at 1 second (FEV1)
      (median 74% versus 86% for bilateral transplants only; p<0.0001), shorter
      unadjusted survival (median 6.09 versus 6.82 years; p<0.001) and increased risk
      of death after adjusting for potential confounders (adjusted hazard ratio 1.13;
      95% CI, 1.03-1.23; p=0.007). CONCLUSIONS: Early rejection is associated with an
      increased incidence of stricture. Recipients with stricture demonstrate worse
      postoperative lung function and survival. Prospective studies may be warranted to
      further assess causality and the potential for coordinated rejection and
      stricture surveillance strategies to improve postoperative outcomes.

PMID- 23870831
TI  - To overcome failure to publish negative findings: the OPEN project.

PMID- 23870832
TI  - Can exercise-related improvements in immunity influence cancer prevention and
      prognosis in the elderly?
AB  - Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of
      cancer deaths occur in individuals aged 65 years or older. One factor that may
      contribute to this is immunosenescence - a canopy term that is used to describe
      age-related declines in the normal functioning of the immune system. There are
      multiple age-related deficits in both the innate and adaptive systems that may
      play a role in the increased incidence of cancer. These include decreased NK-cell
      function, impaired antigen uptake and presentation by monocytes and dendritic
      cells, an increase in 'inflammaging', a decline in the number of naive T-cells
      able to respond to evolving tumor cells, and an increase in functionally
      exhausted senescent cells. There is consensus that habitual physical exercise can
      offer protection against certain types of cancer; however the evidence linking
      immunological mechanisms, exercise, and reduced cancer risk remain tentative.
      Multiple studies published over the last two decades suggest that exercise can
      mitigate the deleterious effects of age on immune function, thus increasing anti
      cancer immunity. The potential ameliorative effect of exercise on these
      mechanisms include evidence that physical activity is able to stimulate greater
      NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent
      senescent cell accumulation in the elderly. Here we discuss the role played by
      the immune system in preventing and controlling cancer and how aging may retard
      these anti-cancer mechanisms. We also propose a pathway by which exercise-induced
      alterations in immunosenescence may decrease the incidence of cancer and help
      improve prognosis in cancer patients. 

PMID- 23870833
TI  - Mild to moderate pulmonary hypertension in liver transplantation.
AB  - BACKGROUND: Patients with pulmonary hypertension (PHTN) are at increased risk for
      worse outcomes post-liver transplant (LT). This study evaluated LT outcomes and
      complications for a large number of LT patients with mild to moderate PHTN.
      MATERIALS AND METHODS: This is a retrospective review of data from 2001 to 2011.
      All cases of PHTN were diagnosed with catheterization (mean pulmonary artery
      pressure) and categorized according to standard criteria: low-mild, 25-29 mm Hg;
      high-mild, 30-34 mm Hg; moderate, 35-44 mm Hg; and severe, >=45 mm Hg. Our center
      protocol excludes most patients with known moderate and severe PHTN from LT.
      Outcomes included early liver function, ventilator time, hospital length of stay,
      and graft and patient survival. RESULTS: We reviewed the cardiac and pulmonary
      records for 1263 patients. There were 102 patients with confirmed PHTN (8%): 63
      low-mild, 30 high-mild, and 9 moderate. Patients with PHTN were older (P <
      0.001). Patients with PHTN were more likely to have prolonged post-transplant
      ventilator weaning (40% versus 26% >48 h post-transplant; P < 0.01) and a longer
      length of hospital stay (12 versus 10 d; P = 0.08). The PHTN had a lower 1-y
      graft survival (79% versus 87%; P = 0.05). There were no statistical differences
      in early graft function or in long-term patient survival. CONCLUSIONS: These
      results suggest that PHTN patients require longer post-liver transplant
      ventilation and length of hospital stay, but have similar early graft function
      and long-term survival. The risk of PHTN in these patients increases with
      increasing age.

PMID- 23870834
TI  - Combined intrathymic and intravenous injection of mesenchymal stem cells can
      prolong the survival of rat cardiac allograft associated with decrease in miR-155
      expression.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to improve graft
      outcomes and promote allograft tolerance. In this study, we examined the effects
      and mechanism of combined intrathymic (i.t.) and intravenous (i.v.) injection of
      MSCs on the survival of transplanted hearts in a rat allograft model. METHODS:
      Recipient Sprague-Dawley rats were transplanted with hearts from Wistar rats.
      Wistar rat MSCs were infused via i.t. or i.v. or combined i.t. and i.v.
      (i.t./i.v.) injection at designated intervals. In vitro mixed lymphocyte reaction
      assays were performed to assess the immunosuppressive capacity of MSCs.
      Mesenchymal stem cell surface markers and CD4+, CD25+, and Foxp3+ T-cells in the
      peripheral blood were detected using flow cytometry analysis. The expression of
      microRNAs and cytokines in graft infiltrating lymphocytes was analyzed by real
      time polymerase chain reaction. RESULTS: The MSCs cultured in vitro had
      multipotential differentiation capacity. Mixed lymphocyte reaction assays showed
      that donor-derived MSCs could not stimulate a proliferative response of recipient
      lymphocytes and could markedly suppress T-cell responses. Survival of the
      allografts was significantly prolonged by administration of i.t./i.v. injection
      of MSCs compared with controls, with a mean survival of 32.2 versus 6.5 d,
      respectively. Compared with the syngeneic groups posttransplant, miR-155
      expression was significantly increased in the allogeneic group, and could be
      restored by injection of MSCs, especially i.t./i.v. injection of MSCs. Moreover,
      i.t./i.v. injection of MSCs decreased the level of interleukin (IL)-2 and
      interferon-gamma, but increased the levels of IL-4 and IL-10 in the allogeneic
      group. More important, i.t./i.v. injection of MSCs was the best way to increase
      the percentage of CD4+, CD25+, and Foxp3+ T-cell peripheral blood. CONCLUSIONS:
      Our results indicated that i.t./i.v. injection of MSCs can prolong the survival
      of rat cardiac allograft, which may be associated with down-regulating miR-155
      expression, a shift in the Th1/Th2 balance, and up-regulation of Treg cells
      expression.

PMID- 23870835
TI  - Palliative and end-of-life care training during the surgical clerkship.
AB  - BACKGROUND: In 2000, the Liaison Committee on Medical Education required that all
      medical schools provide experiential training in end-of-life care. To adhere to
      this mandate and advance the professional development of medical students,
      experiential training in communication skills at the end-of-life was introduced
      into the third-year surgical clerkship curriculum at Wright State University
      Boonshoft School of Medicine. MATERIALS AND METHODS: In the 2007-08 academic
      year, 97 third-year medical students completed six standardized end-of-life care
      patient scenarios commonly encountered during the third-year surgical clerkship.
      Goals and objectives were outlined for each scenario, and attending surgeons
      graded student performances and provided formative feedback. RESULTS: All 97
      students, 57.7% female and average age 25.6 +/- 2.04 y, had passing scores on the
      scenarios: (1) Adult Hospice, (2) Pediatric Hospice, (3) Do Not Resuscitate, (4)
      Dyspnea Management/Informed Consent, (5) Treatment Goals and Prognosis, and (6)
      Family Conference. Scenario scores did not differ by gender or age, but students
      completing the clerkship in the first half of the year scored higher on total
      score for the six scenarios (92.8% +/- 4.8% versus 90.5% +/- 5.0%, P = 0.024).
      CONCLUSIONS: Early training in end-of-life communication is feasible during the
      surgical clerkship in the third-year of medical school. Of all the scenarios,
      "Conducting a Family Conference" proved to be the most challenging.

PMID- 23870836
TI  - Age-related dedifferentiation and compensatory changes in the functional network
      underlying face processing.
AB  - Recent evidence has shown that older adults fail to show adaptation in the right
      fusiform gyrus (FG) to the same face presented repeatedly, despite accurate
      detection of the previously presented face. We used functional magnetic resonance
      imaging to investigate whether this phenomenon is associated with age-related
      reductions in face specificity in brain activity and whether older adults
      compensate for these face-processing deficiencies by increasing activity in other
      areas within the face-processing network, or outside this network. A comparison
      of brain activity across multiple stimulus categories showed that, unlike young
      adults who engaged a number of brain regions specific to face processing, older
      adults generalized these patterns of activity to objects and houses. Also, young
      adults showed functional connectivity between the right FG and its homologous
      region during face processing, whereas older adults did not engage the left FG
      but showed a functional connection between the right FG and left orbitofrontal
      cortex. Finally, this frontotemporal functional connection was activated more
      strongly in older adults who performed better on a face-matching task (done
      outside of the scanner), suggesting increased involvement of this functional link
      for successful face recognition with increasing age. These findings suggest that
      2 neural mechanisms, dedifferentiation and compensatory neural recruitment,
      underlie age differences in face processing. 

PMID- 23870837
TI  - Transgenic expression of beta1 antibody in brain neurons impairs age-dependent
      amyloid deposition in APP23 mice.
AB  - Heterologous expression of the functional amyloid beta (Abeta) antibody beta1 in
      the central nervous system was engineered to maximize antibody exposure in the
      brain and assess the effects on Abeta production and accumulation in these
      conditions. A single open reading frame encoding the heavy and light chains of
      beta1 linked by the mouth and foot virus peptide 2A was expressed in brain
      neurons of transgenic mice. Two of the resulting BIN66 transgenic lines were
      crossed with APP23 mice, which develop severe central amyloidosis. Brain
      concentrations at steady-state 5 times greater than those found after peripheral
      beta1 administration were obtained. Similar brain and plasma beta1 concentrations
      indicated robust antibody efflux from the brain. In preplaque mice, beta1 formed
      a complex with Abeta that caused a modest Abeta increase in brain and plasma. At
      11 months of age, beta1 expression reduced amyloid by 97% compared with age
      matched APP23 mice. Interference of beta1 with beta-secretase cleavage of amyloid
      precursor protein was relatively small. Our data suggest that severely impaired
      amyloid formation was primarily mediated by a complex of beta1 with soluble
      Abeta, which might have prevented Abeta aggregation or favored transport out of
      the brain. 

PMID- 23870838
TI  - Reduced neuroplasticity in aged rats: a role for the neurotrophin brain-derived
      neurotrophic factor.
AB  - Aging is a physiological process characterized by a significant reduction of
      neuronal plasticity that might contribute to the functional defects observed in
      old subjects. Even if the neurobiological mechanisms that contribute to such
      impairment remain largely unknown, a role for neurotrophic molecules, such as the
      neurotrophin brain-derived neurotrophic factor (BDNF), has been postulated. On
      this basis, the purpose of this study was to provide a detailed investigation of
      the BDNF system, at transcriptional and translational levels, in the ventral and
      dorsal hippocampus and in the prefrontal cortex of middle-aged and old rats,
      compared with in adult animals. The expression of major players in BDNF
      regulation and response, including the transcription factors, calcium-responsive
      transcription factor, cyclic adenosine monophosphate (cAMP) responsive element
      binding protein (CREB), and neuronal Per Arnt Sim (PAS) domain protein 4, and the
      high-affinity receptor tropomyosin receptor kinase B (TrkB), was also analyzed.
      Our results demonstrate that the BDNF system is affected at different levels in
      aged rats with global impairment including reduced transcription, impaired
      protein synthesis and processing, and decreased activation of the TrkB receptors.
      These modifications might contribute to the cognitive deficits associated with
      aging and suggest that pharmacological strategies aimed at restoring reduced
      neurotrophism might be useful to counteract age-related cognitive decline. 

PMID- 23870840
TI  - Palliative care research in Africa: consensus building for a prioritized agenda.
AB  - CONTEXT: Palliative care research in Africa is in its relative infancy, with
      dedicated financial support extremely limited. Therefore, setting research
      priorities to optimize use of limited resources is imperative. OBJECTIVES: To
      develop a prioritized research agenda for palliative care in Africa. METHODS: We
      used a two-stage process involving palliative care professionals and researchers:
      1) generation of an initial topic list at a consultative workshop of experts and
      2) prioritization of that list using a consensus development process, the nominal
      group technique. RESULTS: Phase 1: 41 topics were generated across five groups,
      with several topics nominated in more than one group. Phase 2: 16 topics and
      three broad thematic areas were identified. The two most prioritized topics
      within each of the three themes were the following: Theme 1: patient, family, and
      volunteers-1) care outcomes and the impact of palliative care as perceived by
      patients and caregivers and 2) palliative care needs of children; Theme 2: health
      providers-1) impact of palliative care training on care and practice and 2)
      integration of palliative care and antiretroviral therapy services; and Theme 3:
      health systems-1) palliative care needs assessments at the micro-, meso-, and
      macro-levels and 2) integration of palliative care into health systems and
      educational curricula. CONCLUSION: Consensus-based palliative care topics
      determined by the study can assist researchers in optimizing limited research
      capacities by focusing on these prioritized areas. Subsequent to the
      identification and publication of the research agenda, concrete steps will be
      undertaken by the African Palliative Care Research Network and other partners to
      help implement it.

PMID- 23870839
TI  - Novel compound heterozygous mutation in TREM2 found in a Turkish frontotemporal
      dementia-like family.
AB  - Triggering receptor expressed on myeloid cells 2 (TREM2) homozygous mutations
      cause Nasu-Hakola disease, an early-onset recessive form of dementia preceded by
      bone cysts and fractures. The same type of mutations has recently been shown to
      cause frontotemporal dementia (FTD) without the presence of any bone phenotype.
      Here, we further confirm the association of TREM2 mutations with FTD-like
      phenotypes by reporting the first compound heterozygous mutation in a Turkish
      family. 

PMID- 23870841
TI  - Public priorities and preferences for end-of-life care in Namibia.
AB  - CONTEXT: Although quality end-of-life care provision is an international public
      health issue, the majority of evidence is not generated in low- and middle-income
      countries that bear a disproportionate burden of progressive illnesses.
      OBJECTIVES: To identify the priorities and preferences of the Namibian public for
      end-of-life care. METHODS: Using a cross-sectional study design, data were
      collected in the country's capital, Windhoek, from November to December 2010.
      RESULTS: In total, 200 respondents were recruited. The mean age was 27 years (SD
      7.5; range 18-69), with nearly all (n = 199; 99.5%) expressing a religious
      affiliation. Being in pain was reported as the most concerning of nine common end
      of-life symptoms and problems (n = 52; 26.1%), and the most important care
      related aspect was having as much information as wanted (n = 144; 72%). The
      majority (64%) would want their end-of-life care to focus on improving their
      quality of life rather than extending it, with 40% not wanting to know if they
      had limited time left to live. Hospital (n = 96; 48%) and home (n = 64; 32%) were
      the most preferred places of death. The most important end-of-life priority was
      keeping a positive attitude (n = 128; 64%). Having had a close relative or friend
      diagnosed with a serious illness was associated with a 2.3 increase in the odds
      of preference for a hospital death (odds ratio = 2.34, P = 0.009, 95% CI 1.23
      4.47). CONCLUSION: This study identified a number of areas that need to be
      pursued in future research to explore factors that may affect patient preferences
      and priorities in end-of-life care in Namibia.

PMID- 23870842
TI  - Clearance of meperidine and its metabolite normeperidine in hemodialysis patients
      with chronic noncancer pain.
AB  - CONTEXT: Normeperidine accumulates in patients with impaired renal function and
      may cause central neurotoxicity. However, some uremic patients still undergo
      meperidine treatment for chronic pain. OBJECTIVES: To prevent normeperidine side
      effects and complications, we investigated the clearance rate and extraction
      ratio of meperidine and normeperidine in hemodialysis patients with chronic pain.
      METHODS: Three hemodialysis patients, with diagnoses of chronic pancreatitis,
      chronic back pain, and intractable intra-abdominal pain, received long-term (more
      than six months) administration of meperidine for chronic noncancer pain. During
      regular hemodialysis, 72 blood samples in total were collected from the afferent
      port, efferent port, and ultradiafiltrate port at eight time points. The plasma
      concentrations of meperidine and normeperidine were determined by high
      performance liquid chromatography. RESULTS: The prehemodialysis plasma
      concentrations of meperidine and normeperidine were 2963 +/- 315 and 2369 +/-
      1974 ng/mL, which declined to 591 +/- 109 and 853 +/- 765 ng/mL, with 80% and 65%
      reduction, respectively. The plasma clearance and extraction ratios of meperidine
      were 22.7 +/- 9.8 mL/minute and 10.1 +/- 5.6% and for normeperidine 26.0 +/- 11.4
      mL/minute and 10.8 +/- 2.5%, respectively. CONCLUSION: Hemodialysis can
      efficiently remove meperidine and its active metabolite, normeperidine, in uremic
      patients receiving long-term meperidine therapy for chronic noncancer pain.

PMID- 23870843
TI  - Economic impact of advanced pediatric cancer on families.
AB  - CONTEXT: Despite emerging evidence of substantial financial distress in families
      of children with complex illness, little is known about economic hardship in
      families of children with advanced cancer. OBJECTIVES: To describe perceived
      financial hardship, work disruptions, income losses, and associated economic
      impact in families of children with advanced cancer stratified by federal poverty
      level (FPL). METHODS: Cross-sectional survey of 86 parents of children with
      progressive, recurrent, or nonresponsive cancer at three children's hospitals.
      Seventy-one families with complete income data (82%) are included in this
      analysis. RESULTS: Parental work disruptions were prevalent across all income
      levels, with 67 (94%) families reporting some disruption. At least one parent
      quit a job because of the child's illness in 29 (42%) families. Nineteen (27%)
      families described their child's illness as a great economic hardship. Income
      losses because of work disruptions were substantial for all families; families at
      or below 200% FPL, however, were disproportionately affected. Six (50%) of the
      poorest families lost more than 40% of their annual income as compared with two
      (5%) of the wealthiest families (P = 0.006). As a result of income losses, nine
      (15%) previously nonpoor families fell from above to below 200% FPL. CONCLUSION:
      The economic impact of pediatric advanced cancer on families is significant at
      all income levels, although poorer families suffer disproportionate losses.
      Development of ameliorative intervention strategies is warranted.

PMID- 23870844
TI  - Delivering men's health interventions in English Premier League football clubs:
      key design characteristics.
AB  - OBJECTIVES: To investigate the key design characteristics of Premier League
      Health (PLH), a national programme of men's health improvement delivered in/by 16
      English Premier League (EPL) football clubs. STUDY DESIGN: Health Trainers (HTs)
      were hired by EPL clubs to deliver PLH. HTs were the focus of investigations
      aimed at identifying the active design characteristics of male-specific health
      promotion interventions. METHODS: Semi-structured interviews led by researchers
      were performed with 13/16 HTs and identified the key design characteristics
      influential in (I) reaching and (II) helping participants adopt health
      improvement interventions delivered in professional football club settings.
      RESULTS: HTs believed that combining the appeal of football alongside EPL clubs,
      offered a unique opportunity to reach adult males, including hard-to-engage-men
      (HTEM). Awareness raising events held on match days aimed to connect with men,
      but outreach activities were especially important for engaging participants.
      Following initial reach, familiar settings, such as the club stadia and community
      venues were also important for ensuring regular involvement in health improvement
      sessions. Interventions shaped around men's health needs and delivered at times
      when participants could more easily attend, were factors which helped to engage
      men. Supportive social environments and a range of exercise modes and delivery
      options were also seen by HTs as being similarly important. Both the informality
      and familiarity of EPL clubs were viewed by HTs as having substantial advantages
      over conventional NHS settings for reaching and engaging men. Importantly, HTs
      contributed substantial skills to the delivery of PLH. CONCLUSION: Although, top
      flight professional football clubs can recruit men, including those regarded as
      hard-to-engage into health improvement programmes, considerable attention to
      delivery refinement is needed to support male participants adopting interventions
      aimed at promoting healthy lifestyles.

PMID- 23870845
TI  - Syndromic surveillance - a public health legacy of the London 2012 Olympic and
      Paralympic Games.

PMID- 23870846
TI  - Educational inequalities in the co-occurrence of mental health and substance use
      problems, and its adult socio-economic consequences: a longitudinal study of
      young adults in a community sample.
AB  - OBJECTIVES: To examine the relationship between the co-occurrence of mental
      health and substance use problems and socio-economic status (SES). STUDY DESIGN:
      A prospective longitudinal study of 808 males and females followed to age 30.
      METHODS: Survey data were used to derive latent classes (profiles) of mental
      health (depression, anxiety) and substance use (alcohol, nicotine, and marijuana
      [cannabis]) problems at age 27. Analyses examined the associations of these
      profiles with earlier educational attainment (high school diploma) and indicators
      of SES at age 30. RESULTS: Latent Class Analysis produced four profiles: a low
      disorder symptoms group, a licit substance use disorder symptoms group (alcohol
      and nicotine), a mental health disorder symptoms group, and a comorbid group.
      Earning a high school diploma by age 21 decreased the odds of belonging to the
      comorbid group or the licit substance use disorder symptoms group when compared
      to the low disorder symptoms group. These disorder profiles also were found to
      adversely impact subsequent adult SES. The adverse impact was more evident in
      income maintenance and wealth accumulation by age 30 than market or non-market
      labour force participation. CONCLUSIONS: Earning a high school diploma lessens
      the risk of co-occurring mental health and substance use problems which
      contribute to economic instability in young adulthood. Findings underscore the
      importance of public health programmes to reduce the incidence of mental health
      and substance use problems and their associated high costs to individuals and to
      society.

PMID- 23870847
TI  - Mediterranean diet, overweight and body composition in children from eight
      European countries: cross-sectional and prospective results from the IDEFICS
      study.
AB  - BACKGROUND & AIMS: A Mediterranean-like dietary pattern has been shown to be
      inversely associated with many diseases, but its role in early obesity prevention
      is not clear. We aimed to determine if this pattern is common among European
      children and whether it is associated with overweight and obesity. METHODS AND
      RESULTS: The IDEFICS study recruited 16,220 children aged 2-9 years from study
      centers in eight European countries. Weight, height, waist circumference, and
      skinfolds were measured at baseline and in 9114 children of the original cohort
      after two years. Diet was evaluated by a parental questionnaire reporting
      children's usual consumption of 43 food items. Adherence to a Mediterranean-like
      diet was calculated by a food frequency-based Mediterranean Diet Score (fMDS).
      The highest fMDS levels were observed in Sweden, the lowest in Cyprus. High
      scores were inversely associated with overweight including obesity (OR = 0.85,
      95% CI: 0.77; 0.94) and percent fat mass (beta = -0.22, 95% CI: -0.43; -0.01)
      independently of age, sex, socioeconomic status, study center and physical
      activity. High fMDS at baseline protected against increases in BMI (OR = 0.87,
      95% CI: 0.78; 0.98), waist circumference (OR = 0.87, 95% CI: 0.77; 0.98) and
      waist-to-height ratio (OR = 0.88, 95% CI: 0.78; 0.99) with a similar trend
      observed for percent fat mass (p = 0.06). CONCLUSIONS: Although a Mediterranean
      dietary pattern is inversely associated with childhood obesity, it is not common
      in children living in the Mediterranean region and should therefore be advocated
      as part of EU obesity prevention strategies.

PMID- 23870848
TI  - Tongue ulcer in a 7-month-old infant.

PMID- 23870849
TI  - Five cases of recalcitrant plantar warts successfully treated with imiquimod 5%
      cream.

PMID- 23870850
TI  - Leprosy. An update: definition, pathogenesis, classification, diagnosis, and
      treatment.
AB  - Leprosy is a chronic granulomatous disease caused by the bacillus Mycobacterium
      leprae. It primarily affects the skin and peripheral nerves and is still endemic
      in various regions of the world. Clinical presentation depends on the patient's
      immune status at the time of infection and during the course of the disease.
      Leprosy is associated with disability and marginalization. Diagnosis is clinical
      and is made when the patient has at least 1 of the following cardinal signs
      specified by the World Health Organization: hypopigmented or erythematous macules
      with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear
      or skin biopsy with loss of adnexa at affected sites. Leprosy is treated with a
      multidrug combination of rifampicin, clofazimine, and dapsone. Two main regimens
      are used depending on whether the patient has paucibacillary or multibacillary
      disease. 

PMID- 23870851
TI  - The minimal erythema dose (MED) project: in search of consensus on phototesting.

PMID- 23870852
TI  - Antimicrobial activity of Amazon Astrocaryum aculeatum extracts and its
      association to oxidative metabolism.
AB  - Several compounds present in fruits as polyphenols are able to kill or inhibit
      the growth of microorganisms. These proprieties are relevant mainly in tropical
      areas, as Amazonian region where infectious are highly prevalent. Therefore, this
      study investigated the antimicrobial activity of tucuma Amazonian fruit against
      37 microorganisms. The potential role of oxidative metabolism imbalance was also
      studied as causal mechanism of antimicrobial activity. The results showed
      antibacterial effect of pulp and peel tucuma hydro-alcoholic extracts on three
      Gram-positive bacteria (Enterococcus faecalis, Bacillus cereus, Listeria
      monocytogenes) and antifungal effect against Candida albicans. The antimicrobial
      contribution of main chemical compounds (quercetin, rutin, beta-carotene and
      gallic, caffeic and chlorogenic acids) found in tucuma extracts was also
      investigated showing an inhibitory effect depending of the organism mainly by
      quercetin in bacteria and rutin in C. albicans. Analysis of kinetic of DNA
      releasing in extracellular medium by fluorescence using DNA Pico Green assay((r))
      and reactive oxygen species production (ROS) showed potential oxidative imbalance
      contribution on tucuma inhibitory effect. In B. cereus and C. albicans this
      effect was clear since after 24h the ROS levels were higher when compared to
      negative control group. In conclusion, tucuma extracts present antimicrobial
      activity to four microorganisms that have large problems of drug resistance, and
      the possible mechanism of action of this Amazon fruit is related to REDOX
      imbalance. 

PMID- 23870854
TI  - miR-148b-nanoparticle conjugates for light mediated osteogenesis of human adipose
      stromal/stem cells.
AB  - Delivery systems providing spatial and temporal control have the potential to
      improve outcomes in surgical reconstruction and regenerative medicine by precise
      modulation of wound healing and tissue repair processes. In this study we
      describe a synthesis and oligonucleotide functionalization process of silver
      nanoparticle complexes for photoactivated microRNA (miRNA) delivery. The activity
      of the PC-miR-148b-SNP construct is demonstrated by light mediated delivery of
      miR-148b mimic resulting in differentiation of human autologous adipose derived
      mesenchymal stromal/stem cells (hASCs) into an osteogenic linage. The conjugate,
      upon photoactivation, increases alkaline phosphatase (ALP) activity in the cell
      membrane and calcification (mineralization) of hASCs on days 7 and 14
      respectively. Additionally, the expression of mRNA for the early, middle and late
      stage osteogenic markers; ALP, RunX2 and osteocalcin (OCN) respectively, was also
      significantly upregulated at days 7 and 28, respectively after photoactivation of
      PC-miR-148b-SNP and release of miR-148b mimics. Additionally, PC-miR-148b-SNP
      conjugate is readily delivered to the intracellular compartment without the use
      of transfection vectors commonly required for free oligonucleotides. This
      technology demonstrates photo-controlled, spatial and temporal modulation of
      osteogenesis in hASCs.

PMID- 23870855
TI  - Rituximab-induced acute severe thrombocytopenia: a case series in patients with
      mantle cell lymphoma.

PMID- 23870856
TI  - Dementia.
AB  - INTRODUCTION: Dementia is characterised by chronic, global, non-reversible
      deterioration in memory, executive function, and personality. Speech and motor
      function may also be impaired. METHODS AND OUTCOMES: We conducted a systematic
      review and aimed to answer the following clinical questions: What are the effects
      of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or
      vascular)? What are the effects of treatments on behavioural and psychological
      symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline,
      Embase, The Cochrane Library, and other important databases up to July 2011
      (Clinical Evidence reviews are updated periodically; please check our website for
      the most up-to-date version of this review). We included harms alerts from
      relevant organisations such as the US Food and Drug Administration (FDA) and the
      UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found
      49 systematic reviews, RCTs, or observational studies that met our inclusion
      criteria. We performed a GRADE evaluation of the quality of evidence for
      interventions. CONCLUSIONS: In this systematic review, we present information
      relating to the effectiveness and safety of the following interventions:
      acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine),
      antidepressants (clomipramine, fluoxetine, imipramine, sertraline),
      antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy,
      benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT),
      cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers
      (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal
      anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and
      statins.

PMID- 23870857
TI  - Grade of ductal carcinoma in situ accompanying infiltrating ductal carcinoma as
      an independent prognostic factor.
AB  - BACKGROUND: Several studies about the relationship between IDC and DCIS have been
      reported, but no consensus has been reached regarding clinical characteristics
      and prognostic value. PATIENTS AND METHODS: We reviewed the medical records of
      patients who underwent surgery for IDC between 2006 and 2008. DCIS adjacent to
      IDC was pathologically classified as either high-grade DCIS or non-high-grade
      DCIS. RESULTS: Among 1751 IDC patients within the study period, 1384 patients
      (79.0%) had concomitant DCIS. There was no survival difference between patients
      with pure IDC and those with IDC and concomitant DCIS. However, patients with
      high-grade DCIS had worse survival than did patients with non-high-grade DCIS or
      pure IDC (5-year recurrence-free survival rates for IDC with non-high-grade DCIS,
      pure IDC without DCIS, and IDC with high-grade DCIS were 97%, 93%, and 86%,
      respectively; P = .001). This tendency was maintained regardless of estrogen
      receptor status or histologic grade of IDC. In a Cox regression model, patients
      with IDC and accompanying high-grade DCIS had a 2.5-fold higher probability of
      local or distant relapse than did those with IDC and low-grade DCIS (hazard
      ratio, 2.51; 95% confidence interval, 1.12-5.64). CONCLUSIONS: The prognosis of
      patients with invasive breast cancer differed according to the grade of
      concomitant adjacent DCIS. Accordingly, the grade of adjacent DCIS should be
      considered as a prognostic factor in the clinical management of patients with
      breast cancer. However, in our study, the follow-up periods were short to confirm
      prognostic effect. Further studies are needed.

PMID- 23870858
TI  - Owning and reducing the cost of health care in the emergency department.

PMID- 23870859
TI  - Is screening women for intimate partner violence in the emergency department
      effective?

PMID- 23870860
TI  - Investing in emergency medicine to improve health care for all Americans: the
      role of the Agency for Healthcare Research and Quality.

PMID- 23870861
TI  - Nature of the interfaces between the constituent phases in the high entropy alloy
      CoCrCuFeNiAl.
AB  - The interfaces between the phase separated regions in the dendritic grains of
      laser-deposited samples of the high entropy alloy CoCrCuFeNiAl have been studied
      using aberration-corrected analytical (scanning) transmission electron microscopy
      ((S)TEM). The compositional variations have been determined using energy
      dispersive x-ray spectroscopy (EDS) in (S)TEM. It was found that between B2,
      consisting mainly of Al, Ni, Co, and Fe, and disordered bcc phase, consisting
      mainly of Cr and Fe, there is a transition region, approximately 1.5 nm in width,
      over which the chemical composition changes from the B2 to that of the bcc phase.
      The crystal structure of this interfacial region is also B2, but with very
      different sublattice occupancy than that of the adjacent B2 compound. The
      structural aspects of the interface between the ordered B2 phase and the
      disordered bcc phase have been characterized using high angle annular dark-field
      (HAADF) imaging in STEM. It has been determined that the interfaces are
      essentially coherent, with the lattice parameters of the two B2 regions and the
      disordered bcc phase being more or less the same, the uncertainty arising from
      possible relaxations from the proximity of the surfaces of the thin foils used in
      imaging of the microstructures. Direct observations show that there is a planar
      continuity between all three constituent phases.

PMID- 23870862
TI  - Identification, quantification and antioxidant activity of acylated flavonol
      glycosides from sea buckthorn (Hippophae rhamnoides ssp. sinensis).
AB  - A novel acylated flavonol glycoside: isorhamnetin (3-O-[(6-O-E-sinapoyl)-beta-D
      glucopyranosyl-(1->2)]-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside) (1),
      together with two known acylated flavonol glycosides: quercetin (3-O-[(6-O-E
      sinapoyl)-beta-D-glucopyranosyl-(1->2)]-beta-D-glucopyranosyl-7-O-alpha-L
      rhamnopyranoside) (2) and kaempferol (3-O-[(6-O-E-sinapoyl)-beta-D-glucopyranosyl
      (1->2)]-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside) (3) were isolated
      from the n-butanol fraction of sea buckthorn (Hippophae rhamnoides ssp. sinensis)
      berries for the first time by chromatographic methods, and their structures were
      elucidated using UV, MS, (1)H and (13)C NMR, and 2D NMR. Compounds 1-3 showed
      good scavenging activities, with respective IC50 values of 8.91, 4.26 and 30.90
      MUM toward the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical; respective Trolox
      equivalent antioxidant capacities of 2.89, 4.04 and 2.44 MUM MUM(-1) toward 2,2'
      azino-bis-3-ethyl-benzothiazoline-6-sulphonate (ABTS) radical. The quantitative
      analysis of the isolated acylated flavonol glycosides was performed by HPLC-DAD
      method. The contents of compounds 1-3 were in the range of 12.2-31.4, 4.0-25.3,
      7.5-59.7 mg/100 g dried berries and 9.1-34.5, 75.1-182.1, 29.2-113.4 mg/100 g
      dried leaves, respectively.

PMID- 23870863
TI  - Response surface optimization and identification of isothiocyanates produced from
      broccoli sprouts.
AB  - Isothiocyanates (ITCs) are proved as one of natural anticarcinogenic compounds,
      which are produced from the decomposition of glucosinolates by myrosinase. The
      present study optimized the enzymolysis conditions (pH, addition of EDTA and
      ascorbic acid) for ITCs production from glucosinolates in broccoli sprouts using
      response surface methodology. ITCs production was clearly enhanced by a suitable
      pH, addition content of EDTA and ascorbic acid. The optimal enzymolysis
      conditions were determined to be adding EDTA 0.02 mmol and 0.16 mg ascorbic acid
      to 4 ml of the homogenized phosphate-citrate buffer solution (pH 4.00). ITCs
      profiles were identified and seven kinds of individual ITCs were detected, among
      which sulforaphane accounted the most. Four kinds of individual ITCs including
      isobutyl isothiocyanate, 4-isothiocyanato-1-butene, 1-isothiocyanato-3-methyl
      butane and 1-isothiocyanato-butane are firstly reported in broccoli sprouts.

PMID- 23870864
TI  - Protective role of Punica granatum (pomegranate) peel and seed oil extracts on
      diethylnitrosamine and phenobarbital-induced hepatic injury in male rats.
AB  - The present study is an attempt to reveal the protective role of Punica granatum
      peel and seed oil extracts against diethylnitrosamine (DEN) and phenobarbital
      (PB) induced hepatic injury in rats. DEN administration increased the levels of
      malondialdehyde (MDA), DNA fragmentation, caspase-3 and glutathione reductase
      (GSR) activities, while the level of reduced glutathione (GSH) and the activities
      of superoxide dismutase (SOD), glutathione S-transferase (GST) and total
      glutathione peroxidase (t-GPx) were decreased compared with the control.
      Treatment with peel and seed oil extracts pre, during and post DEN administration
      improved liver functions, decreased the levels of MDA, DNA fragmentation, caspase
      3 and GSR activities with an elevation in levels of GSH, SOD, GST and t-GPx
      activities. This indicates that these extracts reduced the oxidative stress and
      apoptosis induced by DEN. Also the effect of administration of PE and SOE
      separately for a long time (23 weeks) on healthy rats was studied.

PMID- 23870865
TI  - Resolution of vitamin A cis/trans isomers resolves proficiency test assessments.
AB  - Proficiency tests run by FAPAS for vitamin A analysis in cod liver oil were
      observed to give rise to multi-modal distributions of data. For this reason,
      setting the assigned value for the tests was difficult or even impossible,
      without too high uncertainty values. The methods used by participants could
      broadly be categorised into normal phase or reversed-phase high performance
      liquid chromatography. In a recent test, participants were asked if their method
      could separate the cis and trans isomers of vitamin A. Results from participants
      who could separate the isomers gave rise to a unimodal distribution of data. This
      was synonymous with participants using the normal phase chromatography method.
      Conversely, results from participants who were unable to separate the isomers, or
      who were using reversed-phase chromatography, gave rise to multi-modal
      distributions of data. The recommendation for future tests is to set the assigned
      value on the basis of the ability to separate the isomers. 

PMID- 23870866
TI  - Headspace components that discriminate between thermal and high pressure high
      temperature treated green vegetables: identification and linkage to possible
      process-induced chemical changes.
AB  - For the first time in literature, this study compares the process-induced
      chemical reactions in three industrially relevant green vegetables: broccoli,
      green pepper and spinach treated with thermal and high pressure high temperature
      (HPHT) processing. Aiming for a fair comparison, the processing conditions were
      selected based on the principle of equivalence. A comprehensive integration of MS
      based metabolic fingerprinting techniques, advanced data preprocessing and
      statistical data analysis has been implemented as untargeted/unbiased
      multiresponse screening tool to uncover changes in the volatile fraction. For all
      vegetables, thermal processing, compared to HPHT, seems to enhance Maillard and
      Strecker degradation reaction, triggering the formation of furanic compounds and
      Strecker aldehydes. In most cases, high pressure seems to accelerate (an)aerobic
      thermal degradation of unsaturated fatty acids leading to the formation of
      aliphatic aldehydes and ketones. In addition, both thermal and HPHT processing
      accelerated the formation of sulfur-containing compounds. This work demonstrated
      that the approach is effective in identifying and comparing different process
      induced chemical changes, adding depth to our perspective in terms of studying a
      highly complex chemical changes occurring during food processing. 

PMID- 23870867
TI  - A new benzoquinone and a new benzofuran from the edible mushroom Neolentinus
      lepideus and their inhibitory activity in NO production inhibition assay.
AB  - The fruiting bodies or mycelia of mushrooms have been used as food and food
      flavoring material for centuries due to their nutritional and medicinal value and
      the diversity of their bioactive components. The present research is the first to
      investigate the bioactive secondary metabolites from the solid culture of the
      edible mushroom Neolentinus lepideus. Two new secondary metabolites, 5
      methoxyisobenzofuran-4,7(1H,3H)-dione (1) and 1,3-dihydroisobenzofuran-4,6-diol
      (2), as well as seven known compounds including one benzoquinone derivative (3)
      and six cinnamic acid derivatives (4-9) were obtained. Their structures were
      established by means of spectroscopic methods, including 1D and 2D NMR. The
      bioactivity on the nitric oxide production in lipopolysaccharide-induced
      macrophages was evaluated for all metabolites (1-9) isolated. Compound 1 showed
      strong NO inhibitory activity with the IC50 value of 6.2 MUM. Compound 2
      displayed moderate NO inhibitory activity with the IC50 value of 88.8 MUM. In the
      DPPH scavenging assay, compound 2 displayed antioxidant activity with IC50 of
      68.6 MUM. The discovery of new NO production inhibitors from N. lepideus expands
      its usage as a functional food.

PMID- 23870868
TI  - A novel method for determination of patulin in apple juices by GC-MS.
AB  - A reliable gas chromatography-mass spectrometry with a QuEChERS procedure has
      been developed and validated for detection and determination of patulin in apple
      juice. This procedure includes initial extraction step with acetonitrile,
      partitioning step by addition of magnesium sulphate, sodium carbonate and sodium
      chloride, and clean-up step using dispersive solid-phase extraction by addition
      of a mixture of magnesium sulphate and primary secondary amine sorbent. In order
      to increase GC adoptability of patulin, derivatisation step was performed using
      N,O-bis-trimethylsilyl trifluoroacetamide. Method recoveries of patulin from
      apple juice samples ranged from 79.9% to 87.9%. Limit of detection (LOD) and
      quantification (LOQ) were 0.4 and 1.3 MUg/L, respectively. Relative standard
      deviations were lower than 9.5%. The developed method has been successfully
      applied to the analysis of patulin in apple juice samples.

PMID- 23870869
TI  - Characterisation of dietary fibre components in cereals and legumes used in
      Serbian diet.
AB  - The typical Serbian diet is characterised by high intake of cereal products and
      also legumes are often used. The content of total fibre as well as certain fibre
      fractions was determined in cereals, cereal products, and cooked legumes. The
      content of total fibre in cooked cereals and cereal products ranged from 2.5 to
      20.8 g/100 g, and in cooked legumes from 14.0 to 24.5 g/100 g (on dry matter
      basis). Distribution of analysed fibre fractions and their quantities differed
      significantly depending on food groups. Fructans and arabinoxylans were the most
      significant fibre fractions in rye flakes, and beta-glucan in oat flakes,
      cellulose and resistant starch were present in significant amounts in peas and
      kidney beans. When the size of regular food portions was taken into
      consideration, the best sources of total dietary fibre were peas and kidney beans
      (more than 11 g/serving). The same foods were the best sources of cellulose (4.98
      and 3.56 g/serving) and resistant starch (3.90 and 2.83 g/serving). High intake
      of arabinoxylans and fructans could be accomplished with cooked wheat (3.20 g and
      1.60 g/serving, respectively). Oat (1.39 g/serving) and barley flakes (1.30
      g/serving) can be recommended as the best sources of beta-glucan.

PMID- 23870870
TI  - Approaches to understanding the contribution of anthocyanins to the antioxidant
      capacity of pasteurized pomegranate juices.
AB  - Influence of processing and storage conditions on anthocyanin stability and
      antioxidant activity of clarified and cloudy juices from arils of the 'Mollar'
      pomegranate variety was studied. Clarification process reduced the content of
      total monomeric and individual anthocyanins, and increased the antioxidant
      activity of pomegranate juice. Thermal treatments (65 and 90  degrees C for 30 or
      5 s) decreased the percentage of polymeric anthocyanin form, increasing on the
      contrary the monomeric one. In any case, storage temperature was the main factor
      affecting all the parameters tested. Cyanidin 3-O-glucoside (Cy3G) was more
      instable than delphinidin 3,5-di (Dp3,5dG) and cyaniding 3,5-diglucosides
      (Cy3,5dG). A linear relationship was observed between oxygen radical absorbance
      capacity (ORAC) and total monomeric anthocyanins, suggesting that they
      contributed strongly to the antioxidant capacity. Results presented in this study
      show that hurdle technology (heating plus refrigeration) may help to reduce
      anthocyanin degradation in pasteurized pomegranate juice, avoiding a dramatic
      impact on its colour and preserving the beneficial effects of this specific
      bioactive compounds on human health.

PMID- 23870871
TI  - Influence of technical processing units on polyphenols and antioxidant capacity
      of carrot (Daucus carrot L.) juice.
AB  - The effect of three processing units (blanching, enzyme liquefaction, and
      pasteurisation) on polyphenols and antioxidant activity of carrot juices was
      investigated. Polyphenols and antioxidant activity of carrot juices varied with
      different processes. Five polyphenolic acids were identified in fresh carrot
      juice, and the predominant compound was chlorogenic acid. Compared with fresh
      carrot juice, blanching and enzyme liquefaction could result in the increase of
      the total polyphenol content (TPC) and the antioxidant activity in scavenging
      DPPH free radicals (DPPH) and Fe(2+)-chelating capacity (FC), whereas
      pasteurisation could result in the decrease of the TPC and the antioxidant
      activity in DPPH and FC. Meanwhile blanching, enzyme liquefaction, and
      pasteurisation showed little influence on the antioxidant activity in lipid
      peroxidation protection. The antioxidant activities in DPPH and FC increased with
      increasing concentration while no correlation between lipid peroxidation
      protection and polyphenols concentration. Polyphenols still retained high
      antioxidant activity after the processes, which have potential health benefits
      for consumers. 

PMID- 23870872
TI  - Purification and characterization of calcium-binding soybean protein hydrolysates
      by Ca2+/Fe3+ immobilized metal affinity chromatography (IMAC).
AB  - Soybean protein hydrolysates (SPHs) can bind calcium in order to form soluble
      peptide-calcium complexes. However, amino acid composition and structural
      characteristics of the calcium chelating SPHs are still unclear. This study
      separated SPHs with calcium and iron immobilized metal affinity chromatography
      (IMAC), and examined the effects of SPHs with different amino acid composition on
      calcium binding capacity. Three fractions (FFe-1, FFe-2 and FFe-3) isolated with
      IMAC-Fe(3+) were shown possessing increased Glu, Gln, Lys and Pro content from
      FFe-1 to FFe-3, and improved amount of bound calcium. Furthermore, the fractions
      adsorbed on IMAC-Ca(2+) (Fe(3+)) were separated and identified with reverse-phase
      (RP)-HPLC and MALDI-TOF MS/MS. The results showed that the sequence of peptides
      from FCa-2 and FFe-3 fractions was DEGEQPRPFPFP. 

PMID- 23870873
TI  - Effect of processing on the detectability of peanut protein by ELISA.
AB  - Chicken IgY was used for the detection and quantification of peanut proteins by
      indirect competitive ELISA. The method was optimized by using a checker board
      approach to determine the optimal concentration of coating antigen, primary
      antibody and secondary antibody. Peanut protein could be detected in foods down
      to levels of 10 ppm. The effect of physical (heat treatment at 80  degrees C and
      100  degrees C) and chemical (acid, alkali and reducing sugar) treatments on the
      IgY binding of peanut proteins was investigated. The optimized assay was
      relatively sensitive for the roasted peanut proteins. However, the binding
      ability of chicken IgYs to peanut proteins was found to be significantly altered
      by denaturation and hydrolysis of proteins. It was also observed that the effect
      of Millard chemistry on the detectability of peanut protein was less pronounced
      at high temperatures than at low temperatures.

PMID- 23870874
TI  - Effects of chitosan, aqueous extract of ginger, onion and garlic on quality and
      shelf life of stewed-pork during refrigerated storage.
AB  - Effects of 1% or 0.5% chitosan (CHI), 10% or 5% aqueous extract of ginger, onion
      and garlic (GOG) and their composite solutions (1% CHI+10% GOG, 0.5% CHI+5% GOG)
      on quality and shelf life of stewed-pork were evaluated. Microbiological (total
      bacterial count), chemical (pH, total volatile basic nitrogen (TVB-N), peroxide
      value (POV), 2-thiobarbituric acid (TBA)) and sensory characteristics were
      analysed periodically during refrigerated storage at 4  degrees C for 12 days.
      CHI and/or GOG treatments retarded the increases in pH, TVB-N, POV, TBA and total
      bacterial count. CHI showed better antibacteria but weaker antioxidation than
      GOG. Composite treatment had possible synergistic effect while the high
      concentration of composite solution (Mix1) had adverse effect on odour and
      overall acceptance. Mix2, the diluted solution of Mix1, could be a natural
      promising preservative for the stewed-pork considering the comprehensive effects
      of antioxidation, antibacteria and sensory quality, which could extend the shelf
      life for about 5-6 days.

PMID- 23870875
TI  - An attempt to cast light into starch nanocrystals preparation and cross-linking.
AB  - Potato starch was hydrolyzed with 2.2 or 3.7 M hydrochloric acid in order to
      obtain the nanocrystals which afterwards were chemically cross-linked with sodium
      hexametaphosphate. The stronger acidity resulted in smaller nanocrystals with
      mean size of 48 nm in a shorter time. X-ray diffraction confirmed the dominant
      crystalline nature of particles and Fourier transform infrared spectroscopy
      suggested the presence of lower number of free hydroxyl groups in nanocrystals
      after cross-linking. Starch nanocrystals showed two distinctive differential
      scaning colorimetry endotherms at 26 and 125  degrees C, attributed to
      destruction of nanocrystals lattice and moblizing of each nanocrystal's
      structure, respectively. Cross-linking resulted in a tenacious spatial
      arrangement of nanocrystals, strengthening the crystals lattice against phase
      transitions induced by heating. Scanning electron microscopy images confirmed the
      particle size measured for nanocrystals by light scattering. Atomic force
      microscopy topographic images suggested that starch nanocrystals were originated
      from small amylopectin blocklets in granular assembly of starch.

PMID- 23870876
TI  - Comparison of chitosan-gelatin composite and bilayer coating and film effect on
      the quality of refrigerated rainbow trout.
AB  - The effect of chitosan-gelatin coating and film on the rancidity development in
      rainbow trout (Oncorhynchus mykiss) fillets during refrigerated storage (4+/-1 
      degrees C) was examined over a period of 16 days. Composite and bilayer coated
      and film wrapped fish samples were analysed periodically for microbiological
      (total viable count, psychrotrophic count) and chemical (TVB-N, POV, TBARS, FFA)
      characteristics. The results indicated that chitosan-gelatin coating and film
      retained their good quality characteristics and extend the shelf life of fish
      samples during refrigerated storage .The coating was better than the film in
      reducing lipid oxidation of fillets, but there was no significant difference
      between them in control of bacterial contamination.

PMID- 23870877
TI  - Ester synthesis and hydrolysis in an aqueous environment, and strain specific
      changes during malolactic fermentation in wine with Oenococcus oeni.
AB  - Previous work has shown that Oenococcus oeni produces esterases that are capable
      of hydrolysing artificial substrates. Using SPME-GCMS, this study provides
      evidence that purified O. oeni esterases have the ability to both synthesise and
      hydrolyse esters. Two purified esterases (EstA2 and EstB28) synthesised ethyl
      butanoate and ethyl hexanoate to varying degrees. Both purified esterases
      hydrolysed ethyl butanoate, ethyl hexanoate and ethyl octanoate. Once this dual
      activity was confirmed, malolactic fermentation (MLF) trials were conducted in
      wine with O. oeni strains that had been previously observed to have either high
      or low esterase activity against artificial substrates. Strain specific
      differences were observed and strains with low esterase hydrolysis activity
      against artificial substrates had a higher level of total esters measured after
      MLF. The results demonstrate the impact that O. oeni has on wine aroma and
      relates this to the ester hydrolysis and synthesis abilities of O. oeni strains. 

PMID- 23870878
TI  - Comparison of three officinal Chinese pharmacopoeia species of Glycyrrhiza based
      on separation and quantification of triterpene saponins and chemometrics
      analysis.
AB  - The dried roots and rhizomes of Glycyrrhiza species, named licorice, have been
      utilized as food as well as crude drugs in China for thousands of years.
      Glycyrrhiza species can be differentiated based on the morphologic features of
      their aerial part, i.e. leaf and fruit morphologies, but not on their root
      morphology, even though that is the medicinal part. In this paper, a fast and
      effective UPLC-TQ-MS/MS method was explored for better identification and
      quantitative investigation of triterpene saponins in licorice, which laid basis
      for chemical comparison of three officinal Chinese pharmacopoeia Glycyrrhiza
      species. The results showed that all of these licorice samples were rich in
      triterpene saponins but with significant difference corresponding to different
      Glycyrrhiza species. The proposed method could be useful in quality control and
      standardization of licorice raw materials and its products. 

PMID- 23870879
TI  - Effects of phytate and minerals on the bioavailability of oxalate from food.
AB  - Phytate and mineral cations are both considered as important dietary factors for
      inhibiting the crystallisation of calcium oxalate kidney stones in susceptible
      individuals. In this paper, the phytate and mineral composition of whole bran
      cereals (wheat, barley and oat) and legumes were determined together with their
      soluble and insoluble oxalate concentrations in order to investigate the effects
      on oxalate solubility. The oat bran sample had the highest soluble oxalate
      concentration at 79+/-1.3 mg/100 g, while total and soluble oxalate
      concentrations in the food samples studied range from 33 to 199 mg/100 g and 14
      to 79 mg/100 g, respectively. The phytate concentration was in the range from 227
      to 4393 mg/100 g and the concentrations of cations were in the range 54-70 mg/100
      g for calcium, 75-398 mg/100 g for magnesium, 244-1529 mg/100 g for potassium and
      4-11 mg/100 g for iron. Soluble oxalate concentration did not increase in
      proportion to total oxalate, and the phytate concentration in all foods was
      sufficient to contribute to an increase in soluble oxalate concentration by
      binding calcium.

PMID- 23870880
TI  - Analysis of non-polar heterocyclic aromatic amines in beefburguers by using
      microwave-assisted extraction and dispersive liquid-ionic liquid microextraction.
AB  - A new sample preparation procedure to determine six heterocyclic aromatic amines
      (3-Amino-1,4-dimethyl-5H-pirido[4,3-b]indole, 3-Amino-1-methyl-5H-pirido[4,3
      b]indole, 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, 2-amino-9H-pyrido
      [2,3-b] indole, 2-amino-3-methyl-9H-pyrido-[2,3-b] indole and 2-Amino-1,6
      dimethylimidazo [4,5-b]-pyridine) in cooked beefburguers by using a combination
      of microwave-assisted solvent extraction and dispersive liquid-liquid
      microextraction with an ionic liquid generated in situ was used. The optimized
      microwave extraction procedure consisted of a clean-up step with n-heptane and a
      subsequent dissolution step in basic media to desorb the analytes from the
      matrix. Next, an aqueous solution of the ionic liquid 1-octyl-3-methylimidazolium
      tetrafluorborate and sodium hexafluorphosphate was added and a water-insoluble 1
      octyl-3-methylimidazolium hexafluorphosphate was formed within the matrix sample.
      The amines were analyzed by liquid chromatography with fluorescence and diode
      array detection by using a typical C18 column. Peak identities were confirmed by
      absorbance spectral matching. Repeatability (RSD%) between 5.4% and 10.9%,
      enrichment factors between 19 and 30, limits of detection between 0.35 and 2.4 ng
      mL(-1) and recoveries between 69% and 100% were achieved. The extraction
      methodology is simple, rapid (about 40 min/sample) cheap and green since small
      amounts of non-toxic solvents are necessary.

PMID- 23870881
TI  - The methionine precursor DL-2-hydroxy-(4-methylthio)butanoic acid protects
      intestinal epithelial barrier function.
AB  - DL-2-hydroxy-(4-methylthio)butanoic acid (HMTBA) is a source of dietary
      methionine (Met) that is widely used in poultry nutrition. We have previously
      shown that HMTBA is preferentially diverted to the transsulfuration pathway,
      which gives antioxidant metabolites such as taurine and glutathione. Therefore,
      here we hypothesize that this Met source can protect epithelial barrier function
      in an in vitro model of intestinal inflammation of Caco-2 cells. The results show
      that HMTBA prevents the increase in paracellular permeability induced by H2O2 or
      tumour necrosis factor-alpha. This effect can be attributed to the increased
      production of taurine and reduced glutathione. Similar results were obtained for
      DL-Met, although the protective role of the amino acid was less pronounced than
      that of the hydroxy analogue. In conclusion, the diversion to the
      transsulfuration pathway means that this Met precursor is of greater value than
      previously thought, due to its capacity to improve intestinal homeostasis and the
      quality of poultry products destined for human consumption.

PMID- 23870882
TI  - Qualitative and quantitative analysis of anthraquinones in rhubarbs by high
      performance liquid chromatography with diode array detector and mass
      spectrometry.
AB  - Rhubarb is well known in traditional Chinese medicines (TCMs) mainly due to its
      effective purgative activity. Anthraquinones, including anthraquinone derivatives
      and their glycosides, are thought to be the major active components in rhubarb.
      To improve the quality control method of rhubarb, we studied on the extraction
      method, and did qualitative and quantitative analysis of widely used rhubarbs,
      Rheum tanguticum Maxim. ex Balf. and Rheum palmatum L., by HPLC-photodiode array
      detection (HPLC-DAD) and HPLC-mass spectrum (HPLC-MS) on a Waters SymmetryShield
      RP18 column (250 mm * 4.6 mm i.d., 5 MUm). Amount of five anthraquinones was
      viewed as the evaluating standard. A standardized characteristic fingerprint of
      rhubarb was provided. From the quantitative analysis, the rationality was
      demonstrated for ancestors to use these two species of rhubarb equally. Under
      modern extraction methods, the amount of five anthraquinones in Rheum tanguticum
      Maxim. ex Balf. is higher than that in Rheum palmatum L. Among various extraction
      methods, ultrasonication with 70% methanol for 30 min is a promising one. For
      HPLC analysis, mobile phase consisted of methanol and 0.1% phosphoric acid in
      water with a gradient program, the detection wavelength at 280nm for
      fingerprinting analysis and 254 nm for quantitative analysis are good choices.

PMID- 23870883
TI  - Acid induced gelation of soymilk, comparison between gels prepared with lactic
      acid bacteria and glucono-delta-lactone.
AB  - The objective of this work was to compare the gelation of soymilk particles
      induced by the acidification of a commercial starter culture with that resulting
      by addition of glucono-delta-lactone (GDL). Structure formation was followed
      using rheology, and the microstructure was observed by confocal microscopy.
      Acidification of lactic acid bacteria resulted in a higher gelation pH (pH 6.29+/
      0.05) compared to that of a gel induced by GDL (pH 5.9+/-0.04). This difference
      was attributed to the longer time available for rearrangements of the soymilk
      particles in soymilk with starter cultures compared to the fast acidification by
      GDL. In spite of the earlier gelation pH, there were no observed differences in
      the final gel stiffness measured at pH 5.1, the value of tan delta, the frequency
      dependence and the linear viscoelastic range of the gels measured at the final
      pH. Microstructural observations also showed a similar protein network structure.

PMID- 23870884
TI  - Global metabolomic profiling of human serum from obese individuals by liquid
      chromatography-time-of-flight/mass spectrometry to evaluate the intake of
      breakfasts prepared with heated edible oils.
AB  - The metabolic profile of human serum after intake of breakfasts prepared with
      different heated vegetable oils has been studied. Four oils (olive and sunflower
      oils, pure and enriched with natural and artificial oxidation inhibitors) were
      subjected to a simulated heated process prior to breakfast preparation. A
      metabolomics global profiling approach performed on post-basal serum samples
      revealed statistical differences among individuals based on breakfast intake, and
      identified compounds responsible for such differences. Serum samples obtained in
      basal state (control samples) and 2 and 4h after programmed intakes were analyzed
      by LC-TOF/MS. The resulting fingerprints were compared and differences between
      basal and post-basal states evaluated, observing that the intake of different
      breakfasts altered the metabolic signature of serum. Analysis models based on PLS
      algorithms were developed to discriminate individuals in post-basal state for
      each intervention breakfast. Then, Volcano tests enabled to detect significant
      molecular entities explaining the variability associated to each breakfast. It is
      worth emphasizing the importance of fatty acids, their derivatives and
      phospholipids for tentative identification. 

PMID- 23870885
TI  - Sacha inchi (Plukenetia volubilis): a seed source of polyunsaturated fatty acids,
      tocopherols, phytosterols, phenolic compounds and antioxidant capacity.
AB  - Fatty acids (FA), phytosterols, tocopherols, phenolic compounds, total
      carotenoids and hydrophilic and lipophilic ORAC antioxidant capacities were
      evaluated in 16 cultivars of Sacha inchi (SI) seeds with the aim to valorise them
      and offer more information on the functional properties of SI seeds. A high alpha
      linolenic (alpha-Ln) fatty acid content was found in all cultivars (omega3, 12.8
      16.0 g/100 g seed), followed by linoleic (L) fatty acid (omega6, 12.4-14.1g/100g
      seed). The ratio omega6/omega3 was within the 0.83-1.09 range. gamma- and delta
      tocopherols were the most important tocopherols, whereas the most representative
      phytosterols were beta-sitosterol and stigmasterol. Contents of total phenolics,
      total carotenoids and hydrophilic and lipophilic antioxidant capacities ranged
      from 64.6 to 80 mg of gallic acid equivalent/100g seed; from 0.07 to 0.09 mg of
      beta-carotene equivalent/100g of seed; from 4.3 to 7.3 and, from 1.0 to 2.8 MUmol
      of Trolox equivalent/g of seed, respectively, among the evaluated SI cultivars.
      Results showed significant differences (p<0.05) among the evaluated SI cultivars
      in the contents of omega3, omega6, antioxidant capacities and other evaluated
      phytochemicals. SI seeds should be considered as an important dietary source of
      health promoting phytochemicals.

PMID- 23870886
TI  - Carotenoid contents of extruded and non-extruded sweetpotato flours from Papua
      New Guinea and Australia.
AB  - Carotenoid contents of extruded and non-extruded flours of Papua New Guinean and
      Australian sweetpotato cultivars were studied, using spectrophotometry and high
      performance liquid chromatography (HPLC). The cultivars differed (p<0.05) in
      their total carotenoid and beta-carotene contents, and the Original Beauregard
      cultivar had the highest total carotenoid and beta-carotene contents among the
      cultivars. The spectrophotometry (84-1720 MUg/g solids) method generally over
      estimated the total carotenoid content compared to the more specific HPLC (23-355
      MUg/g solids) method. Extrusion significantly (p<0.05) decreased the DeltaL(*)
      Hunter colour values, while the Deltaa(*), Deltab(*), total colour change
      (DeltaE), chroma (CR), and browning indices (BI) increased. With the extruder and
      screw configuration used, extrusion at 40% moisture and 300 rpm screw speed
      retained carotenoid maximally at more than 80%. This study reports, for the first
      time, carotenoids of flours from south Pacific sweetpotato cultivars, and
      carotenoid retention during extrusion.

PMID- 23870887
TI  - Occurrence of Fusarium mycotoxins in Italian cereal and cereal products from
      organic farming.
AB  - In the present study, the occurrence of eighteen mycotoxins, nine trichothecenes
      (deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol, nivalenol,
      neosolaniol, diacetoxyscirpenol, fusarenon-X, T-2 toxin and HT-2 toxin), three
      zearalenones (zearalenone, alpha-zearalenol and beta-zearalenol), and six
      emergent mycotoxins, beauvericin and five enniatins (A, A1, B, B1 and B4), was
      monitored in different Italian organic cereals and cereal products by using a
      liquid chromatography coupled to triple quadrupole mass spectrometry method. A
      total of 93 organic cereal samples (wheat, barley, rye and oat) were collected
      from Italy. Limits of quantification ranged from 5 to 15 MUg/kg. 80% of analyzed
      samples contained mycotoxins. The occurrence was 33%, 6.5%, 2%, 27%, 7%, 10% and
      43% for deoxynivalenol, HT-2, T-2, nivalenol, zearalenone, beauvericin and
      enniatins, respectively. The major mycotoxin found was enniatin B4; it was
      detected in 40% of all analyzed samples and its levels ranged from 5.7 to 284.2
      MUg/kg. Risk assessment was evaluated by EDI calculations which were lower than
      TDI for all legislated Fusarium mycotoxins.

PMID- 23870888
TI  - DNA barcoding for detecting market substitution in salted cod fillets and
      battered cod chunks.
AB  - The Italian Ministry of Agricultural, Food and Forestry Policies (MiPAAF) Decree
      dated 31 January 2008, which reports the Italian name for fish species of
      commercial interest, establishes that baccala can be obtained exclusively from G.
      macrocephalus (Pacific cod) and G. morhua (Atlantic cod). This paper describes
      the COI-based DNA identification system to verify the substitution or misbranding
      of gadoid fish species and, consequently, its concordance with the labels on
      salted cod fillets shown as baccala and on battered cod chunks labelled as
      bocconcini di baccala. The analysis of interpretable sequences revealed that
      55/65 dried salted cod fillet samples were detected as belonging to the family
      Gadidae, while 10/65 samples appeared to belong to the Lotidae family, while
      among battered cod chunks labelled as bocconcini di baccala, the post-sequencing
      data analysis shows that the labels were completely wrong, with 28/40 samples
      from Pollachius virens and 12/40 samples from Brosme brosme. The substitution
      rate for products labelled on the market as baccala in this study raises
      significant issues relating to food safety and consumer protection. 

PMID- 23870889
TI  - Phenolic composition and inhibitory effect against oxidative DNA damage of cooked
      cowpeas as affected by simulated in vitro gastrointestinal digestion.
AB  - Cowpeas contain phenolic compounds with potential health benefits. The effect of
      simulated gastrointestinal digestion on phenolic composition of cooked cowpeas
      and the ability of the digests to inhibit radical-induced DNA damage was
      determined. A red and a cream-coloured cowpea type were used. The phenolic
      composition of acetone extracts and enzyme digests of cooked cowpeas was
      determined using UPLC-MS. Compounds such as p-hydroxybenzoic acid, p-coumaric
      acid, coumaroylaldaric acid and feruloylaldaric acid were present in the acetone
      extracts of the cooked cowpeas but were not detected in the enzyme digests.
      Glycosides of quercetin and myricetin decreased upon in vitro gastrointestinal
      digestion of cooked cowpeas whereas flavan-3-ols were hardly present except
      catechin glucoside. The enzyme digest of the red cowpea type was about thrice as
      effective as that of the cream cowpea type in protecting DNA from oxidative
      damage. The observation that enzyme digests of cooked cowpeas inhibited radical
      induced DNA damage suggests that cowpea phenolics retain some radical scavenging
      activity after gastrointestinal digestion. 

PMID- 23870890
TI  - Analysis of the flavonoid component of bioactive New Zealand manuka (Leptospermum
      scoparium) honey and the isolation, characterisation and synthesis of an unusual
      pyrrole.
AB  - The flavonoid components of New Zealand manuka (Leptospermum scoparium) honey
      have been quantified in a series of 31 honeys of varying non-peroxide
      antibacterial activity to clarify discrepancies between previous studies reported
      in the literature. Total flavonoid content was 1.16 mg/100 g honey. The principal
      flavonoids present were pinobanksin, pinocembrin, luteolin and chrysin and
      together these represented 61% of the total flavonoid content. 1, 2-formyl-5-(2
      methoxyphenyl)-pyrrole, which was weakly correlated with the non-peroxide
      antibacterial activity, was isolated from the flavonoid fraction and separately
      synthesised. 1 did not display inhibitory activity against Staphylococcus aureus
      in vitro and thus the origin of the correlation, which is still unknown, is not a
      direct contribution.

PMID- 23870891
TI  - Effect of whey protein agglomeration on spray dried microcapsules containing
      Saccharomyces boulardii.
AB  - This work investigates the effect of whey protein agglomeration on the
      survivability of Saccharomyces boulardii within spray dried microcapsules. It
      attempts to go beyond phenomenological observations by establishing a
      relationship between physicochemical characteristics of the polymeric matrix and
      its effect on probiotic endurance upon spray drying. It is well known that this
      type of thermal shock has lethal consequences on the yeast cells. To avoid such
      undesirable outcome, we take advantage of the early agglomeration phenomenon
      observed for whey protein by adjusting the pH value of preparations close to
      isoelectric point (pH 4-5). During the subsequent process of spray drying,
      development of whey protein agglomerates induces formation of an early crust, and
      the protein in this molten globular state creates a cohesive network
      encapsulating the yeast cells. It appears that the early crust formation at a
      given sample pH and temperature regime during spray drying benefits the
      survivability of S. boulardii within microcapsules. 

PMID- 23870892
TI  - Comparison of LFA with PCR and RPLA in detecting SEB from isolated clinical
      strains of Staphylococcus aureus and its application in food samples.
AB  - Three sensitive and specific assays, the lateral flow assay (LFA), polymerase
      chain reaction assay (PCR) and reversed passive latex agglutination assay (RPLA),
      were selected for detection of staphylococcal enterotoxin B (SEB) from 77
      clinical Staphylococcus aureus strains isolated from humans. Analytical results
      revealed that the LFA has almost the same detection sensitivity as that of PCR
      and RPLA. The concordances between the 3 assays were as follows: LFA-PCR, 92.2%;
      LFA-RPLA, 94.8%; and PCR-RPLA, 97.4%. For further evaluation, the LFA was used
      for the detection of SEB in different food matrices. The assay was able to
      successfully identify SEB in a wide variety of food samples at levels as low as
      10 ng/mL in less than 10 min. This study proved that the LFA is an excellent tool
      for detection of SEB both in isolated clinical S. aureus strains and in food
      specimens and may prove particularly important as an early warning tool to
      prevent food poisoning in consumers.

PMID- 23870893
TI  - Simultaneous determination of eighteen steroid hormones in antler velvet by gas
      chromatography-tandem mass spectrometry.
AB  - A method for the simultaneous determination of eighteen steroid hormones,
      including 17alpha-ethinylestradiol, 17alpha-estradiol, 19-nortestosterone,
      estriol, testosterone, androsterone, 17beta-estradiol, estrone, progesterone,
      17alpha-hydroxyprogesterone, medroxyprogesterone, norethisterone acetate,
      testosterone 17-propionate, medroxyprogesterone-17-acetate, corticosterone,
      megestrol-17-acetate, chlromadinone-17-acetate and 17beta-estradiol-benzoate, in
      antler velvet was developed by solid-phase extraction (SPE) and gas
      chromatography-tandem mass spectrometry (GC-MS/MS). Prior to the determination by
      GC-MS/MS, the analytes were derivatized with heptafluorobutyric acid anhydrides
      (HFBA). The recoveries were in the range of 62.13-104.00% for eighteen compounds
      at concentration levels (5-500 MUg/L) and relative standard deviations (RSDs)
      were lower than 17.15%. The detection limits were from 0.2 to 22.3 MUg/kg for the
      steroid hormones. The developed method was rapid, sensitive and successfully
      applied to the determination of steroid hormones in antler velvet samples
      collected from three countries.

PMID- 23870894
TI  - A green and effective approach for characterisation and quality control of
      chrysanthemum by pressurized hot water extraction in combination with HPLC with
      UV absorbance detection.
AB  - Chrysanthemum is a ubiquitous plant with many species and wide uses, and it is
      usually consumed as functional food. The main aim of this paper is to demonstrate
      that chromatographic fingerprints obtained from the HPLC/UV analysis of the
      pressurized hot water extraction (PHWE) extracts together with the aid of
      principal component analysis (PCA), allowed for the clustering of various
      chrysanthemums of different species and provenance. In addition, a parallel study
      of pressurized fluid extraction (PFE) with methanol was carried out for
      comparison. From the results, a clearer separation and clustering was obtained
      with the environmentally-benign water extracts compared with methanol extracts.
      This study shows that PHWE in combination with HPLC/UV and PCA can be used
      successfully as a green and effective approach for characterisation and quality
      control of ubiquitous functional food such as chrysanthemum. 

PMID- 23870895
TI  - Myoglobin as marker in meat adulteration: a UPLC method for determining the
      presence of pork meat in raw beef burger.
AB  - The identification of meat animal species used in raw burgers is very important
      with respect to economic and religious considerations. Therefore, international
      supervisory bodies have implemented procedures to control the employed meat
      species. In this paper we propose myoglobin as a powerful molecular marker to
      evaluate the presence of non-declared meat addition in raw beef burgers by using
      ultra-performance liquid chromatography (UPLC) for the separation and
      identification of edible animal species (beef, chicken, horse, ostrich, pig and
      water buffalo). Meat samples were pre-treated with sodium nitrite to transform
      oxymyoglobin and deoxymyoglobin to the more stable metmyoglobin. The developed
      method was validated, preparing mixtures with different percentages of pork and
      beef minced meat. The obtained results show that using myoglobin as marker, 5%
      (25 mg/500 mg) of pork or beef meat can be detected in premixed minced meat
      samples.

PMID- 23870896
TI  - Determination of vanillin in commercial food product by adsorptive stripping
      voltammetry using a boron-doped diamond electrode.
AB  - A method for the determination of food additive vanillin was developed by
      adsorptive stripping voltammetry. Its determination was carried out at the
      anodically pre-treated boron-doped diamond electrode in aqueous solutions. Using
      square-wave stripping mode, the compound yielded a well-defined voltammetric
      response in phosphate buffer, pH 2.5 at +1.14 V (vs. Ag/AgCl) (a pre
      concentration step being carried out at open-circuit condition for 60s). A linear
      calibration graph was obtained in the concentration range of 0.5-15.0 MUg mL(-1)
      (3.3*10(-6)-9.8*10(-5) mol L(-1)) with a detection limit of 0.024 MUg mL(-1)
      (1.6*10(-7) mol L(-1)). As an example, the practical applicability of the
      proposed method was tested for the determination of this flavouring agent in
      commercial pudding powder of Keshkule (Turkish milk pudding with almond flour).

PMID- 23870897
TI  - Detection of extraction artifacts in the analysis of honey volatiles using
      comprehensive two-dimensional gas chromatography.
AB  - Extraction using headspace solid phase microextraction (HS-SPME) coupled to
      comprehensive two-dimensional gas chromatography with flame ionisation detection
      (GC*GC-FID) was employed to evaluate the effect of SPME fractionation conditions
      (heating time and temperature) on the generation of artifacts. The occurrence of
      artifacts was more pronounced at higher fractionation temperatures and times
      which caused significant changes in the chromatographic profiles. The
      identification of the volatile fraction of the honey blend was performed through
      a two-dimensional gas chromatograph coupled to a mass spectrometer with time of
      flight analyser (GC*GC-ToFMS) by comparing the first dimension linear temperature
      programmed retention index ((1)D-LTPRI) with the peak's identities provided by
      the mass spectral similarity search. Several artifacts were found and identified 
      such as hydroxymethylfurfural, methyl-furone and furfural - and some of them
      were not previously detected as such in honey samples. These compounds were
      either the result of hydrolysis or thermal decomposition of components already
      present in the honey samples. This occurrence was attributed to the increased
      detectability provided by GC*GC compared to conventional GC. The possible
      emergence of previously unknown extraction artifacts as a general tendency
      related use of GC*GC instead of conventional GC is discussed as a result of these
      observations. 

PMID- 23870899
TI  - Phenethyl isothiocyanate inhibits hypoxia-induced accumulation of HIF-1alpha and
      VEGF expression in human glioma cells.
AB  - Phenethyl isothiocyanate (PEITC), a natural dietary isothiocyanate, inhibits
      angiogenesis but the molecular mechanisms that underlie this effect are not
      known. In this study, under hypoxic conditions (1% O2), we examined the effect of
      PEITC on the intracellular level of the hypoxia inducible factor (HIF-1alpha) and
      extracellular level of the vascular endothelial growth factor (VEGF) in a variety
      of human cancer cell lines. Surprisingly, we observed that PEITC suppressed the
      HIF-1alpha accumulation during hypoxia in human glioma U87, human prostate cancer
      DU145, colon cancer HCT116, liver cancer HepG2, and breast cancer SkBr3 cells.
      PEITC treatment also significantly reduced the hypoxia-induced secretion of VEGF.
      Suppression of HIF-1alpha accumulation during treatment with PEITC in hypoxia was
      related to PI3K and MAPK pathways. Taken together, these results suggest that
      PEITC inhibits the HIF-1alpha expression through inhibiting the PI3K and MAPK
      signalling pathway and provide a new insight into a potential mechanism of the
      anticancer properties of PEITC. 

PMID- 23870898
TI  - Effect of sorbitan monostearate on the physical characteristics and whipping
      properties of whipped cream.
AB  - In this work, the effects of sorbitan monostearate (Span 60) level on the
      particle size distribution, microstructure and apparent viscosity of the emulsion
      were investigated. Average particle size (d4,3), surface protein concentration,
      partial coalescence of fat and overrun of whipped cream during whipping were also
      determined. As Span 60 level increased (0-0.8%) in emulsion, the apparent
      viscosity was increased gradually, and the particle size range was narrowed,
      which was also detected by microstructure. A positive effect of whipping time was
      observed on the average particle size, partial coalescence of fat, surface
      protein concentration and overrun during whipping, respectively. An increase of
      Span 60 level resulted in a reduction of d4,3 values and partial coalescence of
      fat during 0-1 min whipping, then increasing after whipping for 2-5 min (0.6%
      Span 60 as the critical level). A negative behaviour was observed between surface
      protein concentration and Span 60. Moreover, Span 60 could improve the overrun
      and organoleptic properties of whipped cream efficiently.

PMID- 23870900
TI  - Determination of heterocyclic amines in braised sauce beef.
AB  - A simplified and improved analysis method to determine the content of
      heterocyclic amines (HAs) was developed. Samples were extracted with ethyl
      acetate, and macrosubstances were removed by centrifugation. The eluent used
      consisted of methanol/ammonia water (9:1, v/v), and the eluates were directly
      mixed for further HPLC analysis. A binary mobile phase consisting of 0.05 M
      ammonium acetate-acetic acid and acetonitrile was used for the separation of 12
      HAs, and the excitation and emission wavelengths of 3-amino-1-methyl-5H
      pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) were adjusted to
      the same 315 and 410 nm, respectively. This method was further applied to
      determine the content of HAs in "Jiang Niu Rou", namely braised sauce beef. Nine
      kinds of HAs were found in the samples and the total amounts of HAs ranged from
      4.33 to 27.15 ng/g. The sterilized samples contained more HAs than un-sterilized
      samples.

PMID- 23870901
TI  - Screening alpha-glucosidase inhibitor from natural products by capillary
      electrophoresis with immobilised enzyme onto polymer monolith modified by gold
      nanoparticles.
AB  - A novel strategy for screening alpha-glucosidase inhibitors (AGIs) from natural
      products by capillary electrophoresis (CE) with an immobilised enzyme
      microreactor was developed. In this approach, gold nanoparticles (AuNPs) was
      first covalently attached to surface of the pores of the porous polymer capillary
      monolith via the formation of an Au-S bond, and alpha-glucosidase was then simply
      and stably immobilised onto AuNPs through the strong affinity of gold for amino
      groups of the enzyme. In order to profiling the activity of the immobilised alpha
      glucosidase, the natural substrate was hydrolyzed by it and the yield of product
      was determined by CE. The amount of covalently attached alpha-glucosidase to the
      monolith was calculated to be about 30.0 MUg/mg. The immobilised enzyme exhibited
      80% activity after 25 runs, and only lost 7.6% of activity after 6 runs within 31
      days. Screening of AGIs present in extracts of natural products by the proposed
      method was demonstrated.

PMID- 23870902
TI  - ESR spectroscopic properties of irradiated gum Arabic.
AB  - Electron spin resonance (ESR) spectra of irradiated gum Arabic with doses between
      0.5 and 5 kGy were studied. A linear relationship between the absorbed dose and
      the intensities of the ESR spectra was observed. ESR spectra of irradiated gum
      Arabic showed a decay of relative concentrations of free radicals originated by
      radiation and the production of at least two species of free radicals with half
      times: 3.3 and 125.4 h. The results of spectral simulations for these radical
      groups were giso=2.0046; A=1.2 mT and gx=gy=2.0062, gz=2.0025. Hydration and
      dehydration of irradiated gum Arabic returns the ESR spectrum to its initial
      state before irradiation. The results show that ESR can be used as simple and
      reliable method to detect irradiated gum Arabic up to 60 days after initial
      radiation with doses on the order of 5 kGy.

PMID- 23870903
TI  - Comparison of a silver nanoparticle-based method and the modified
      spectrophotometric methods for assessing antioxidant capacity of rapeseed
      varieties.
AB  - The antioxidant capacity of 15 rapeseed varieties was determined by the proposed
      silver nanoparticle-based (AgNP) method and three modified assays: ferric
      reducing antioxidant power (FRAP), 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and
      Folin-Ciocalteu reducing capacity (FC). The average antioxidant capacities of the
      studied rapeseed cultivars ranged between 5261-9462, 3708-7112, 18864-31245 and
      5816-9937 MUmol sinapic acid (SA)/100g for AgNP, FRAP, DPPH and FC methods,
      respectively. There are significant, positive correlations between antioxidant
      capacities of the studied rapeseed cultivars determined by four analytical
      methods (r=0.5971-0.9149, p<0.05). The comparable precision for the proposed AgNP
      method (RSD=1.4-4.4%) and the modified FRAP, DPPH and FC methods (RSD=1.0-4.4%,
      0.7-2.1% and 0.8-3.6%, respectively), demonstrate the benefit of the AgNP method
      in the routine analysis of antioxidant capacity of rapeseed cultivars. The
      principal component analysis (PCA) and hierarchical cluster analysis (HCA) were
      used for discrimination the quality of the studied rapeseed varieties based on
      their antioxidant potential determined by different analytical methods. Three
      main groups were identified by HCA, while the classification and characterisation
      of rapeseed varieties within each of these groups were obtained from PCA. The
      chemometric analyses demonstrated that, rapeseed variety S13 had the highest
      antioxidant capacity, thus this cultivar should be considered as the richest
      source of natural antioxidants.

PMID- 23870904
TI  - High resolution TaqMan real-time PCR approach to detect hazelnut DNA encoding for
      ITS rDNA in foods.
AB  - A broad range of foods have been described as causing allergies, but the majority
      of allergic reactions can be ascribed to a limited number of food components.
      Recent extensive surveys showed how tree nuts, particularly hazelnut (Corylus
      avellana L.) seeds, rank amongst the most important sources of food allergy. In
      order to protect the allergic consumer, efficient and reliable methods are
      required for the detection of allergenic ingredients. For this purpose, we have
      developed a real-time polymerase chain reaction (PCR) for detection of hazelnut
      in commercial food products. In this way a specific hazelnut primer pair based on
      the ITS marker (70 bp) and a nuclease (TaqMan) probe labelled with FAM and BHQ
      were designed. Sensibility of real-time PCR was determined by analysis of raw and
      heat treated hazelnut-wheat flour mixtures with a range of detection of 0.1
      100,000 ppm. Practical applicability of the real-time PCR assay developed for
      determining hazelnut in different food matrices was investigated by analyzing 179
      commercial foodstuffs comprising snacks, biscuits, chocolates, bonbons, creams,
      nut bars, ice creams, precooked meals, breads, beverages, yogurts, cereals, meat
      products, rice cake and nougat. From the total of samples analyzed, 40 commercial
      food products that didn't declare hazelnut nor traces on the label were found to
      contain hazelnut. The real-time PCR method proposed herein due to its high
      sensitivity facilitates the detection of hazelnut traces in commercial food
      products and can also be useful for monitoring the effectiveness of cleaning
      processes and as consequence, can help to prevent the food allergic consumer from
      unintentional ingestion of hidden allergens.

PMID- 23870905
TI  - Air-assisted liquid-liquid microextraction-gas chromatography-flame ionisation
      detection: a fast and simple method for the assessment of triazole pesticides
      residues in surface water, cucumber, tomato and grape juices samples.
AB  - A recently reported microextraction technique namely air-assisted liquid-liquid
      microextraction (AALLME) has been described for the extraction/preconcentration
      of some triazole pesticides from different samples prior to gas chromatography
      flame ionisation detection (GC-FID). This technique is similar to dispersive
      liquid-liquid microextraction (DLLME) but in this method there is no need to use
      a disperser solvent and also volume of the used extraction solvent is less than
      DLLME. In this study, toluene with a density lower than that of water was used as
      an extraction solvent. Under the optimum extraction conditions, the method showed
      wide linear ranges with R(2)>0.996 and low limits of detection and quantification
      between 0.53-1.13 and 1.76-3.77 ng mL(-1), respectively. Enrichment factors (EFs)
      and extraction recoveries (ERs) were in the ranges of 713-808 and 100-113%,
      respectively. Relative standard deviations (RSDs) for the extraction of 25 and
      250 ng mL(-1) of each selected triazole pesticide were less than 7% for intra-day
      (n=6) and inter-days (n=5) precision. The method was successfully used for
      analytes determination in different surface water, grape juice, cucumber, and
      tomato samples.

PMID- 23870906
TI  - Identification of quinoline, carboline and glycinamide compounds in cow milk
      using HRMS and NMR.
AB  - The aim of this work was to characterise new UV-absorbing compounds (UAC) in cow
      milk in order to gain an overview of the molecular diversity of the minor
      bioactive constituents, that could be used to trace animal feed or that
      potentially affect milk quality. UAC were extracted from lyophilized milks,
      partitioned using SPE C-18 cartridges, purified by semi-preparative HPLC then
      analysed by HPLC/DAD/HRMS in both ESI(-) and ESI(+) ionisation mode. Compounds
      that remained unidentified after comparison with UV and MS databases were
      analysed by 1D and 2D NMR techniques. The identification and structural
      elucidation of N-cinnamoylglycine, 2,4-, 2,6-, 2,8-quinolinediols, and 1-methyl-3
      carboxy-beta-carboline are described. 

PMID- 23870907
TI  - Differences between conventional and glyphosate tolerant soybeans and moisture
      effect in their discrimination by near infrared spectroscopy.
AB  - Previous studies showed that Near Infrared Spectroscopy (NIRS) could distinguish
      between Roundup Ready(r) (RR) and conventional soybeans at the bulk and single
      seed sample level, but it was not clear which compounds drove the classification.
      In this research the varieties used did not show significant differences in major
      compounds between RR and conventional beans, but moisture content had a big
      impact on classification accuracies. Four of the five RR samples had slightly
      higher moistures and had a higher water uptake than their conventional
      counterparts. This could be linked with differences in their hulls, being either
      compositional or morphological. Because water absorption occurs in the same
      region as main compounds in hulls (mainly carbohydrates) and water causes
      physical changes from swelling, variations in moisture cause a complex
      interaction resulting in a large impact on discrimination accuracies. 

PMID- 23870908
TI  - Comparison of the milk-clotting properties of three plant extracts.
AB  - Several proteases from plant sources have been proposed as milk coagulants,
      however, limited research has been done on their milk-clotting properties. The
      effect of temperature on the milk-clotting activity of kiwi fruit, melon and
      ginger extracts was evaluated, as well as the effects of the different extracts
      on curd properties. Melon extracts showed high milk-clotting activity over a
      broad temperature range (45-75  degrees C) while kiwi fruit and ginger extracts
      showed high activity over a narrower temperature range, with a maximum at 40 and
      63  degrees C, respectively. Curds produced using kiwi extracts had textural
      properties comparable with those obtained using commercial rennet, while melon
      extracts produced a fragile gel and low curd yield. The milk-clotting behavior of
      the three plant extracts was related to the protease specificity present in these
      extracts. The kiwi proteases displayed chymosin-like properties and thus hold the
      best potential for use as a milk coagulant in cheese production.

PMID- 23870909
TI  - A combined approach for characterisation of fresh and brined vine leaves by X-ray
      powder diffraction, NMR spectroscopy and direct infusion high resolution mass
      spectrometry.
AB  - X-ray powder diffraction was combined, for the first time, with Nuclear Magnetic
      Resonance spectroscopy and direct infusion mass spectrometry to characterise
      fresh and brined grape leaves. Covariance analysis of data generated by the three
      techniques was performed with the aim to correlate information deriving from the
      solid part with those obtained for soluble metabolites. The results obtained
      indicate that crystalline components can be correlated to the metabolites
      contained in the grape leaves, paving the way to the use of X-ray diffraction
      analysis for food fingerprinting purposes. Moreover it was ascertained that,
      differently from most of the metabolites present in the fresh vine leaves,
      linolenic acid (an omega-3-fatty acid) and quercetin-3-O-glucuronide (a
      polyphenol metabolite) do not undergo sensible degradation during the brining
      process, which is used as preservative method for the grape leaves. 

PMID- 23870910
TI  - Heavy metals determination in water and food samples after preconcentration by a
      new nanoporous adsorbent.
AB  - In this work, SBA-15 mesoporous silica has been chemically functionalized with
      guanidin groups. The resulting material has been characterised and employed as
      solid phase extractant for preconcentration of Pb(2+), Cu(2+), Zn(2+) and Cd(2+)
      ions. The ions were identified by flame atomic absorption spectrometry (FAAS).
      The enrichment factor of the proposed method was 100 and detection limits were
      found to be 4.5, 0.6, 0.2 and 0.5 ng mL(-1) for Pb(2+), Cu(2+), Zn(2+) and Cd(2+)
      respectively. The time and the optimum amount of the sorbent, pH and minimum
      amount of acid for stripping and break through volume were investigated. The
      maximum capacity the adsorbent was found to be 89.1 (+/-1.7) MUg, 57.2 (+/-1.6)
      MUg, 26.8 (+/-1.6) MUg and 36.0 (+/-0.6) MUg of Pb(2+), Cu(2+), Zn(2+) and Cd(2+)
      per mg functionalized SBA-15, respectively. Guanidin functionalized SBA-15 was
      successfully applied as a new solid extractant for the simultaneous
      preconcentration of Pb(2+), Cu(2+), Zn(2+) and Cd(2+) ions in water and food
      samples.

PMID- 23870911
TI  - Combination of low dose of genistein and daidzein has synergistic preventive
      effects on isogenic human prostate cancer cells when compared with individual soy
      isoflavone.
AB  - The reduced incidence of prostate cancer (PCa) in Asia countries has been
      attributed to high soy diets, and major soy isoflavones, in particular daidzein
      and genistein, are thought to be the source of the beneficial and anti-cancer
      effects of soy foods. However, attention has been drawn to the safety of using
      high levels of soy isoflavones in humans, which is especially the concern for
      consumers taking regular soy isoflavone dietary supplements. The main objective
      of this study is thus to identify a soy isoflavone combination with lower levels
      of daidzein and genistein to be a more efficacious and safer chemo-preventive
      agent for PCa. The anticancer effects of daidzein and genistein, and their
      combinations on early-stage androgen-dependent PCa cells (LNCaP) and bone
      metastatic LNCaP-derivative PCa cells (C4-2B) were compared. Cells were treated
      with varying concentrations of daidzein, genistein (25-200 MUM) or their
      combinations (25 or 50 MUM) and cell proliferation, apoptosis, cell cycles and
      cellular uptakes of the isoflavones were measured after 48 h. Daidzein and
      genistein showed a synergistic effect on inhibiting cell proliferation and
      inducing apoptosis of both PCa cells. Twenty-five MUM daidzein/50 MUM genistein
      and 50 MUM daidzein/50 MUM genistein significantly increased the apoptotic
      effects on C4-2B cells although they did not show any effect when used
      individually. Except 50 MUM daidzein/50 MUM genistein, all other combinations had
      no impacts on cell cycles. For treatment with soy isoflavone combination,
      genistein was always better taken up than daidzein by both LNCaP and C4-2B cells.

PMID- 23870912
TI  - Enzymatic production of trans fatty acid free fat from partially hydrogenated
      soybean oil (PHSO)--theory, strategy and practicability.
AB  - Development of an advanced process/production technology for healthful fats
      constitutes a major interest of plant oil refinery industry. In this work, a
      strategy to produce trans fatty acid (TFA) free (or low TFA) products from
      partially hydrogenated soybean oil by lipase-catalysed selective hydrolysis was
      proposed, where a physically founded mathematic model to delineate the multi
      responses of the reaction as a function of selectivity factor was defined for the
      first time. The practicability of this strategy was assessed with commercial
      trans-selective Candida antarctica lipase A (CAL-A) as a model biocatalyst based
      on a parameter study and fitting to the model. CAL-A was found to have a
      selectivity factor 4.26 and to maximally remove 73.3% of total TFAs at 46.5%
      hydrolysis degree. 

PMID- 23870913
TI  - Spectrophotometric determination of iron in environmental and food samples using
      solid phase extraction.
AB  - A simple, selective and highly sensitive extraction method has been developed for
      the determination of iron(II) spectrophotometrically after solid phase
      extraction. The absorbance is measured at lambdamax 644 nm. Beer's law was obeyed
      up to 450 ng mL(-1) of iron. The molar absorptivity, Sandell's sensitivity,
      detection and quantification limits were calculated and found to be 1.09*10(5) L
      mol(-1) cm(-1), 0.51 ng cm(-2), 1.98 and 6.0 ng mL(-1), respectively and compared
      with parameters obtained without using solid phase extraction method. After
      reduction of Fe(III) by addition of 2.0 mL of 10% hydroxylamine HCl, the system
      was applied to the total iron. The interference of various ions has been studied
      in detail and the statistical evaluation of the experimental results is reported.
      The proposed methods have been successfully applied for the determination of
      trace amount of iron in environment water, soil and botanical reference materials
      with recovery range (98.71-101.51%).

PMID- 23870914
TI  - Evaluation of anti-oxidant and anti-cancer properties of Dendropanax morbifera
      Leveille.
AB  - Dendropanax morbifera Leveille, an endemic species in Korea, is best known as a
      tree that produces a resinous sap. Although D. morbifera is used in folk
      medicine, its biological activities are poorly understood. In this study, the
      methanolic extracts of D. morbifera branches, debarked stems, bark, and two
      different stages of leaves were evaluated for anti-oxidant activity and anti
      cancer potential. The debarked stem extract exhibited strong 1,1-diphenyl-2
      picrylhydrazyl (DPPH) scavenging activity and reducing power compared with other
      samples. In addition, the cytotoxic activities of these extracts were
      investigated in human tumour cell lines. The results suggested that the extracts
      of debarked stems, green leaves, and yellow leaves were the potent source of anti
      cancer compounds, particularly in Huh-7 cells. Furthermore, treatment with the
      extracts of debarked stems, green leaves, and yellow leaves caused an increase of
      apoptotic or senescent cells in Huh-7 cells. Twenty-four hour treatment with
      debarked stems extract resulted in the strong induction of p53 and p16, whereas
      both leaf extracts inhibited the activation of ERK. The debarked stems and green
      leaf extracts reduced Akt levels in Huh-7 cells, indicating that D. morbifera
      extracts caused the activation of p16 and p53 pathways. This, together with the
      inhibition of Akt or ERK signalling, resulted in suppression of Huh-7 cell
      proliferation. These results suggest that methanolic leaf and debarked stems
      extracts are a source of anti-oxidant and anti-cancer compounds, and could be
      developed as a botanical drug.

PMID- 23870915
TI  - The suitability of the simplified method of the analysis of coffee infusions on
      the content of Ca, Cu, Fe, Mg, Mn and Zn and the study of the effect of
      preparation conditions on the leachability of elements into the coffee brew.
AB  - A fast and straightforward method of the analysis of coffee infusions was
      developed for measurements of total concentrations of Ca, Cu, Fe, Mg, Mn and Zn
      by flame atomic absorption spectrometry. Its validity was proved by the analysis
      of spiked samples; recoveries of added metals were found to be within 98-104%
      while the precision was better than 4%. The method devised was used for the
      analysis of re-distilled water infusions of six popular ground coffees available
      in the Polish market. Using the mud coffee preparation it was established that
      percentages of metals leached in these conditions varied a lot among analysed
      coffees, especially for Ca (14-42%), Mg (6-25%) and Zn (1-24%). For remaining
      metals, the highest extractabilities were assessed for Mn (30-52%) while the
      lowest for Fe (4-16%) and Cu (2-12%). In addition, it was found that the water
      type and the coffee brewing preparation method influence the concentration of
      studied metals in coffee infusions the most. 

PMID- 23870916
TI  - Optimal extraction and fingerprint analysis of Cnidii fructus by accelerated
      solvent extraction and high performance liquid chromatographic analysis with
      photodiode array and mass spectrometry detections.
AB  - A confirmatory and reliable procedure has been developed for extraction and
      determination of Cnidii fructus by accelerated solvent extraction (ASE) and high
      performance liquid chromatography coupled with photodiode array, electrospray
      ionisation ion trap tandem mass spectrometry and time of flight mass spectrometry
      (HPLC-PDA-ESI-ITMS(n)/TOF-MS). The determination method enabled the
      characterisation of sixteen bioactive components in C. fructus and quantification
      of three major coumarins, namely osthole, imperatorin and isopimpinellin.
      Response surface methodology (RSM) was employed to optimise the extraction
      parameters yielding the optimum conditions of ASE (extraction temperature 122 
      degrees C, extraction time 5 min and two static cycles). And the total contents
      of three major coumarins extracted by ASE under the optimum conditions was
      significantly higher than those by reflux and ultrasonic extraction (P<0.05) with
      better reproducibility. At last, the proposed method coupled with pattern
      recognition was applied to analysis of C. fructus from eight different regions in
      China.

PMID- 23870917
TI  - Protective effect of Spirulina platensis enriched in phenolic compounds against
      hepatotoxicity induced by CCl4.
AB  - Phenolic compounds make up the major secondary metabolites with high
      pharmaceutical potential. Microalgae were reported to contain low amounts of
      phenolic compounds. The present study aimed to investigate the hepatoprotective
      potential of biomass of Spirulina platensis enriched in phenolic compounds. The
      protective effects of the biomass of S. platensis with low amounts of phenolics
      (SP1) and with high amounts of phenolics (SP2) against CCl4-induced acute
      hepatotoxicity were evaluated in rats. The increased levels of ALT, AST and MDA
      along with decreased activities of SOD and CAT were significantly (p<0.01)
      ameliorated by SP2. Histological examinations revealed that SP2 was more potent
      than SP1 in protecting the liver from toxic injury of CCl4 and preserving the
      hepatocyte ultrastructure. The lesions including necrosis, lymphocyte
      infiltration, ballooning degeneration and hepatocyte injury as irregular lamellar
      organisation, dilations in endoplasmic reticulums and the presence of great
      number of cytoplasmic vacuolization were healed by SP2. 

PMID- 23870918
TI  - A label-free electrochemical impedance immunosensor based on AuNPs/PAMAM-MWCNT
      Chi nanocomposite modified glassy carbon electrode for detection of Salmonella
      typhimurium in milk.
AB  - A sensitive and stable label-free electrochemical impedance immunosensor for the
      detection of Salmonella typhimurium was developed by immobilising anti-Salmonella
      antibodies onto the gold nanoparticles and poly(amidoamine)-multiwalled carbon
      nanotubes-chitosan nanocomposite film modified glassy carbon electrode
      (AuNPs/PAMAM-MWCNT-Chi/GCE). Electrochemical impedance spectroscopy (EIS) and
      cyclic voltammetry (CV) were used to verify the stepwise assembly of the
      immunosensor. Co-addition of MWCNT, PAMAM and AuNPs greatly enhanced the
      sensitivity of the immunosensor. The immobilisation of antibodies and the binding
      of Salmonella cells to the modified electrode increased the electron-transfer
      resistance (Ret), which was directly measured with EIS using [Fe(CN)6](3-/4-) as
      a redox probe. A linear relationship of Ret and Salmonella concentration was
      obtained in the Salmonella concentration range of 1.0*10(3) to 1.0*10(7) CFU mL(
      1) with a detection limit of 5.0*10(2) CFU mL(-1). Additionally, the proposed
      method was successfully applied to determine S. typhimurium content in milk
      samples with satisfactory results.

PMID- 23870919
TI  - Structural characterization of a A-type linked trimeric anthocyanin derived
      pigment occurring in a young Port wine.
AB  - A new trimeric flavylium derivative pigment was detected for the first time in a
      young Port wine and structurally characterised using both API-LC ESI MS/MS and
      NMR techniques. Its structure comprises a malvidin-3-glucoside molecule (terminal
      unit) linked to two units of flavans (extension units) involving two A-type
      linkages (C4->C8 and C7-O-C2 ether linkages). The energies of the minimized
      geometries for all four conformations of this compound were calculated and
      comparing the structures of all isomers, it was verified that the binding mode
      (alpha or beta) between the first and second anthocyanin unit does not have a key
      role in the compound stability. However, for isomers 1 and 2 where the
      interaction between the second and third anthocyanin units occurs by a "beta"
      mode in opposition to the "alpha" mode verified in isomers 3 and 4, revealed a
      higher stability. The presence of these compounds in red wines is thought to
      result from their extraction from grape skin during fermentation, as the presence
      of these trimeric pigments was detected in a grape skin extract by API-LC ESI
      MS/MS spectrometry.

PMID- 23870920
TI  - Chemical characterisation of two Australian-grown strawberry varieties by using
      comprehensive two-dimensional gas chromatography-mass spectrometry.
AB  - The volatile compositions of two strawberry varieties ('Albion' and 'Juliette')
      grown in Australia were analysed with comprehensive two-dimensional gas
      chromatography (GC*GC) combined with time-of-flight mass spectrometry (ToFMS). A
      suitable data processing method was created that should be sufficiently robust to
      compare sample chromatograms within a harvest season as well as between seasons
      with relative ease. Ninety-four compounds were tentatively or positively
      identified between the two varieties of which 20 have apparently not been
      previously reported to be components of strawberry volatiles. It was determined
      that Albion and Juliette have comparable total soluble solids content close to 11
      degrees Brix. However, since Juliette exhibited a lower titratable acidity
      content than Albion, it consequently has a slightly larger sugar/acid ratio. The
      presence of 2,5-dimethyl-4-hydroxy-(2H)-furan-3-one (furaneol) was detected only
      in Juliette and this variety also had a higher area percentage of 2,5-dimethyl-4
      methoxy-(2H)-furan-3-one (mesifuran), according to the sampling protocol. These
      experimental results offer possible explanations as to why Juliette is perceived
      to have a sweeter flavour than Albion. 

PMID- 23870921
TI  - Development of a real-time PCR method for the identification of Atlantic mackerel
      (Scomber scombrus).
AB  - A Real Time-PCR method based on TaqMan technology for the identification of
      Scomber scombrus has been developed. A system of specific primers and a Minor
      Groove Binding (MGB) TaqMan probe based on sequences of the mitochondrial
      cytochrome b region was designed. The method was successfully tested in 81
      specimens of S. scombrus and related species and validated in 26 different
      commercial samples. An average Threshold Cycle (Ct) value of 15.3 was obtained
      with S. scombrus DNA. With the other species tested fluorescence signal was not
      detected or Ct was significantly higher (P<0.001). The efficiency of the assay
      was estimated to be 92.41%, with 100% specificity, and no cross reactivity was
      detected with any other species. These results reveal that the developed method
      is a rapid and efficient tool to unequivocally identify S. scombrus and may aid
      in the prevention of fraud or mislabelling in mackerel products. 

PMID- 23870922
TI  - Oxidative modification of a proline-rich gliadin peptide.
AB  - Prolamins are proline-rich proteins occurring in cereal grains. Prolamins of
      wheat, barley and rye, or gluten protein, can cause coeliac disease in
      individuals not tolerating gluten. Degrading harmful prolamins can reduce their
      toxicity. A model peptide sequenced in alpha-gliadin, 33-mer
      (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF), was chosen for our study. The metal
      catalysed oxidation of 33-mer was studied, instead of enzymatic hydrolysis.
      Peptide 33-mer was treated in several oxidative systems. Iron-catalysed hydrogen
      peroxide-induced oxidation showed the greatest modification of 33-mer. Carbonyl
      groups and dityrosine cross-links were readily formed. At best, the immunological
      activity of 33-mer was reduced to 18% of its initial level after 24h of
      oxidation. Oxidative treatment can be further applied for the modification of
      cereal prolamin proteins, since it appears to be a potential alternative for
      reduction of coeliac immunological activities in gluten proteins. 

PMID- 23870923
TI  - Density functional study of the antioxidant activity of some recently synthesized
      resveratrol analogues.
AB  - In this paper we have investigated the two main working mechanisms (H atom and
      single-electron transfer) of five new potential antioxidant analogues of cis
      resveratrol. The O-H bond dissociation energy (BDE) and ionization potential (IP)
      key parameters were computed in methanol. Results obtained indicate that all the
      examined compounds are more efficient antioxidants than the molecule from which
      they derive, mainly due to their higher degree of conjugation and the capability
      to delocalize the pi-electrons which contribute to the stabilization of the
      radical species. The enhancement of these stabilizing effects is in part a result
      of the introduction of a single bond between the C2' and C6 carbon atoms of cis
      resveratrol that generates a new central aromatic ring. However, the number of
      hydroxyl groups and in particular the presence of the catechol moiety remains the
      most significant features in determining the order of radical scavenging
      potentiality. Spectroscopic UV-Vis characterization is also reported and
      discussed. 

PMID- 23870924
TI  - Volatile profiles of Italian monovarietal extra virgin olive oils via HS-SPME-GC
      MS: newly identified compounds, flavors molecular markers, and terpenic profile.
AB  - This study aims to contribute to the knowledge of the commercial, sensory, and
      analytical characteristics of extra virgin olive oil (EVOO) from Italy (Marche
      region), renowned since ancient times. Headspace solid-phase micro-extraction (HS
      SPME) was applied for the very first time to the sampling of volatile compounds
      of eleven typical Italian monocultivar EVOOs. Forty-eight compounds were
      characterised by GC-MS, some of them were only occasionally found in other EVOOs
      and some other were never detected before in any EVOO. Compounds belonging mainly
      to alcohols, esters, aldehydes, ketones and hydrocarbons chemical classes
      characterised the volatile profiles. The main volatile compounds detected in the
      EVOOs were the C6 compounds derived from polyunsaturated fatty acids, through the
      lipoxygenase pathway, in different proportion according to the specific cultivar.
      The results suggest that genetic factors strongly influence volatile formation
      and terpene hydrocarbons are claimed to be suitable markers of the geographic
      origin and genotype of the EVOO. Correlations among sensory attributes evaluated
      by a panel test and the presence of specific volatile compounds were highlighted
      for the very first time. The significance of the presence of some newly
      identified volatile compounds was discussed. 

PMID- 23870925
TI  - Novel targeted approach to better understand how natural structural barriers
      govern carotenoid in vitro bioaccessibility in vegetable-based systems.
AB  - An experimental approach, allowing us to understand the effect of natural
      structural barriers (cell walls, chromoplast substructures) on carotenoid
      bioaccessibility, was developed. Different fractions with different levels of
      carotenoid bio-encapsulation (carotenoid-enriched oil, chromoplasts, small cell
      clusters, and large cell clusters) were isolated from different types of carrots
      and tomatoes. An in vitro method was used to determine carotenoid
      bioaccessibility. In the present work, a significant decrease in carotenoid in
      vitro bioaccessibility could be observed with an increasing level of bio
      encapsulation. Differences in cell wall material and chromoplast substructure
      between matrices influenced carotenoid release and inclusion in micelles. For
      carrots, cell walls and chromoplast substructure were important barriers for
      carotenoid bioaccessibility while, in tomatoes, the chromoplast substructure
      represented the most important barrier governing bioaccessibility. The highest
      increase in carotenoid bioaccessibility, for all matrices, was obtained after
      transferring carotenoids into the oil phase, a system lacking cell walls and
      chromoplast substructures that could hamper carotenoid release. 

PMID- 23870926
TI  - Analogues of perillaketone as highly potent agonists of TRPA1 channel.
AB  - Transient receptor potential (TRP) channels represent interesting molecular
      target structures involved in a number of different physiological and
      pathophysiological systems. In particular, TRPA1 channel is involved in
      nociception and in sensory perception of many pungent chemesthetic compounds,
      which are widespread in spices and food plants, including Perilla frutescens. A
      natural compound from P. frutescens (isoegomaketone) and 16 synthetic derivatives
      of perillaketone have been prepared and tested in vitro on rTRPA1 expressed in
      HEK293 cells and their potency, efficacy and desensibilisation activity measured.
      Most derivatives proved to be high potency agonists of TRPA1, with a potency
      higher than most natural agonists reported in the literature. These furylketones
      derivatives, represent a new class of chemical structures active on TRPA1 with
      many potential applications in the agrifood and pharmaceutical industry. 

PMID- 23870927
TI  - Seed maturity differentially mediates metabolic responses in black soybean.
AB  - The soybean seed is placed in the middle of the morphological and developmental
      alterations, such as changes in seed size, weight, and colour, and alteration of
      the composition and contents of metabolites during maturation. In this study, we
      used black soybean seeds to investigate the effect of maturity on metabolite
      levels at different maturity stages. Seeds were sorted into five maturity
      categories, from M1 to M5, based on seed size and external pigmentation. Maturity
      stages M1, M3, and M5 are equivalent to R6, R7, and R8 on the soybean
      reproductive growth stage scale, indicating full seed, beginning maturity, and
      full maturity, respectively. As seed maturation progressed, the seed size
      decreased and the water soluble extract changed, indicating that a change of seed
      pigmentation occurred. At the same time, numerous metabolites responded
      differentially to seed maturation. The partial least squares (PLS) scores plot
      indicated that the metabolic alteration during maturation was clearly visible.
      Furthermore, isoflavones were highly associated with seed maturity on the PLS
      loading plot while fatty acids, glucose, fructose, and sucrose were less linked
      with seed maturity, indicating that those metabolites responded less to seed
      maturation. Overall, the results indicate that each category of metabolites is
      mediated differentially during maturation in black soybean seeds. 

PMID- 23870928
TI  - Monitoring tea fermentation/manufacturing by direct analysis in real time (DART)
      mass spectrometry.
AB  - Factors such as fermentation methods, geographical origin and season can affect
      the biochemical composition of tea leaves (Camellia sinensis L.). In this study,
      the biochemical composition of oolong tea during the manufacturing and
      fermentation process was studied using a non-targeted method utilising ambient
      ionisation with a direct analysis in real time (DART) ion source and mass
      spectrometry (MS). Caffeine dominated the positive ionisation spectra throughout
      the manufacturing process, while the negative ion spectra collected during
      manufacturing were rich in ions likely to be surface lipids. Correlation analyses
      on the spectra revealed two volatile compounds tentatively identified as indole
      and geranic acid, along with ammonium and caffeine clusters/adducts with geranic
      acid that increased in concentration during the fermentation stages of the
      process. The tentative identifications were assigned using a combination of DART
      ion-trap MS(n) and DART-accurate mass MS(1) and MS(2) on tea samples and standard
      compounds. This study highlights the potential of DART-MS to rapidly monitor the
      progress of complex manufacturing processes such as tea fermentation. 

PMID- 23870929
TI  - Pentadecyl ferulate, a potent antioxidant and antiproliferative agent from the
      halophyte Salicornia herbacea.
AB  - An investigation of the chemical constituents of Salicornia herbacea has led to
      the isolation of one new natural product, pentadecyl ferulate (6), together with
      11 known compounds, including phytol (1), stearolic acid (2), gamma-linolenic
      acid (3), (3Z,6Z,9Z)-tricosa-3,6,9-triene (4), linoleic acid (5), stigmasterol
      (7), ergosterol (8), dioctyl phthalate (9), dibutyl phthalate (10), vanillic
      aldehyde (11), and scopoletin (12). The chemical structures of these materials
      were elucidated mainly by spectroscopic analysis. This work represents the first
      recorded example of the isolation of compounds 1, 2, 3, 4, 9, 10, and 11 from S.
      herbacea. The antioxidant experiments revealed that compound 6 possessed strong
      hydroxy radical and superoxide anion scavenging activities and was the principle
      antioxidant ingredient in the ethyl acetate extract. The antiproliferative
      results exhibited that compound 1 selectively inhibited HepG2 cells, whereas
      compounds 3 and 6 showed potent antiproliferative activities against HepG2 and
      A549 cells. 

PMID- 23870930
TI  - Isolation, characterization, and neuroprotective activities of sesquiterpenes
      from Petasites japonicus.
AB  - Neuroprotective reagents to protect the nerve cells against oxidative stress and
      other damages are potentially effective for the medical treatment of Parkinson's
      disease. Petasites japonicus, a wild vegetable, belongs to the family Compositae
      and its extract has shown the neuroprotective effects. A further phytochemical
      investigation of P. japonicus for neuroprotective substances led to the isolation
      of eight new (1-8) and two known (9 and 10) sesquiterpenes. Their structures were
      elucidated on the basis of extensive 1D and 2D NMR (HMQC, HMBC, (1)H-(1)H COSY,
      and NOESY) spectroscopic data analyses, and the structure of 1 was confirmed by X
      ray crystallography. The neuroprotective activities of these sesquiterpenes were
      evaluated against cobalt chloride (CoCl2)-induced neuronal cell death in human
      dopaminergic SH-SY5Y cells. Five compounds showed a neuroprotective activity. 

PMID- 23870931
TI  - Solvent effects and improvements in the deoxyribose degradation assay for
      hydroxyl radical-scavenging.
AB  - The deoxyribose degradation assay is widely used to evaluate the hydroxyl (OH)
      radical-scavenging ability of food or medicines. We compared the hydroxyl radical
      scavenging activity of 25 antioxidant samples prepared in ethanol solution with
      samples prepared after removing the ethanol (residue). The data suggested that
      there was an approximately 9-fold difference between assay results for the
      ethanol solution and residue samples. This indicated a strong alcoholic
      interference. To further study the mechanism, the scavenging activities of 18
      organic solvents (including ethanol) were measured by the deoxyribose assay. Most
      pure organic solvents (especially alcohols) could effectively scavenge hydroxyl
      radicals. As hydroxyl radicals have extremely high reactivities, they will
      quickly react with surrounding solvent molecules. This shows that any organic
      solvent should be completely evaporated before measurement. The proposed method
      is regarded as a reliable hydroxyl radical-scavenging assay, suitable for all
      types of antioxidants. 

PMID- 23870932
TI  - Headspace solid-phase microextraction gas chromatography-mass spectrometry
      determination of volatile compounds in different varieties of African star apple
      fruit (Chrysophillum albidum).
AB  - The volatile compounds in four selected African star apple fruit (Chrysophyllum
      albidum) varieties were isolated and identified using the headspace solid-phase
      microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC
      MS). A total of 59 compounds were identified. Application of the aroma extract
      dilution analysis (AEDA) to the aroma distillates from the fruits revealed 45
      odour-active compounds in the flavour dilution (FD) factor range of 4-128. Among
      them, the highest odour activities (FD factors) were determined for
      methylhexanoate, acetophenone and ethyl dodecanoate. Moreover, aroma
      lipophilicity appears to reflect molecular conformation. Further analysis of the
      similarities and differences between the fruit varieties in terms of the key
      odourants by the application of PLS-DA and PLS-regression coefficient showed
      strong positive correlation between the very sweet/sweet varieties and 10 key
      odourants. The odourants included ethyl acetate, acetyl methyl carbinol,
      methylhexanoate, sabinene, p-cymene, methylbenzoate, ethylbenzoate, geraniol, cis
      alpha-bergomotene, acetophenone, and ethyl dodecanoate. 

PMID- 23870933
TI  - Rapid separation and characterisation of triacylglycerols in ostrich oil by ultra
      performance liquid chromatography coupled with quadrupole time-of-flight mass
      spectrometry.
AB  - The triacylglycerol (TAG) composition of ostrich oil (Struthio camelus) was
      determined by non-aqueous reversed-phase ultra-performance liquid chromatography
      mass spectrometry. Using a column with 150 mm in length, the TAGs were separated
      efficiently with acetonitrile/2-propanol gradient at flow rate of 0.2 mL/min for
      20 min. Detection is performed by positive APCI mass spectrometry, accurate mass
      measurements (<3 ppm) and definite elemental composition for molecular ions and
      fragment ions were obtained to enable characterisation of 24 TAGs in both ostrich
      oil and emu oil. In terms of TAGs composition and contents, the ostrich oils are
      similar to emu oils. This result indicates that the ostrich oil could be a good
      choice of substitution for emu oil, which is expensive and comparatively rare, in
      food, dietetics and cosmetics industry.

PMID- 23870934
TI  - Authenticity of carbon dioxide bubbles in French ciders through multiflow-isotope
      ratio mass spectrometry measurements.
AB  - A procedure to detect whether carbon dioxide was added to French ciders has been
      developed. For this purpose, an optimised and simplified method is proposed to
      determine (13)C/(12)C isotope ratio of carbon dioxide (delta(13)C) in ciders.
      Three critical steps were checked: (1) influence of atmospheric CO2 remaining in
      the loaded vial, (2) impact of helium flush, (3) sampling speed. This study
      showed that atmospheric CO2 does not impact the measurement, that helium flush
      can lead to isotopic fractionation and finally, that a fractionation occurs only
      5h after bottle opening. The method, without any other preparation, consists in
      sampling 0.2 mL of cold (4  degrees C) cider in a vial that is passed in an
      ultrasonic bath for 10 min at room temperature to enhance cider de-carbonation.
      The headspace CO2 is then analysed using the link Multiflow(r)-isotope ratio mass
      spectrometer. Each year, a data bank is developed by fermenting authentic apples
      juices in order to control cider authenticity. Over a four year span (2008-2011),
      the CO2 produced during the fermentation step was studied. This set of 61
      authentic ciders, from various French production areas, was used to determine a
      delta(13)C value range of -22.59+/-0.920/00 for authentic ciders CO2 bubbles. 75
      commercial ciders were analysed with this method. Most of the samples analysed
      present a gas delta(13)C value in the expected range. Nevertheless, some ciders
      have delta(13)C values outside the 3sigma limit, revealing carbonation by
      technical CO2. This practice is not allowed for organic, "Controlled Appellation
      of Origin" ciders and ciders specifying natural carbonation on the label.

PMID- 23870935
TI  - Effects of flavonoids from Rosa laevigata Michx fruit against high-fat diet
      induced non-alcoholic fatty liver disease in rats.
AB  - The effects and mechanisms of the total flavonoids (TFs) from Rosa laevigata
      Michx fruit on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD)
      were investigated in this study. Gavage administration of the TFs significantly
      decreased the relative liver weight, serum AST and ALT activities, the levels of
      serum lipid, LDL, blood glucose and insulin, suppressed lipid accumulation in
      liver, and increased serum HDL level. Moreover, the natural product significantly
      enhanced SOD activity, increased GSH-Px and GSH contents and decreased the
      concentration of MDA and CYP2E1 expression as well as prevented mitochondrial
      membrane potential dysfunctions and ultrastructural alterations. Further
      mechanism investigation indicated that the TFs inhibited hepatic lipid
      accumulation by suppressing the expressions of some key molecules in fatty acid
      synthesis pathway and promoting fatty acid beta-oxidation, while not by
      inhibiting cholesterol synthesis. On the base of these, the TFs should be
      developed as a new drug for treatment of NAFLD.

PMID- 23870936
TI  - Hydrogen peroxide treatment of eggshell membrane to control porosity.
AB  - The eggshell membrane (ESM) is a naturally occurring biological polymer, which
      can be extracted from eggshells, and has been used for adsorption of dyes or
      heavy metals, as a semipermeable membrane to control particle transport, and as a
      natural biocompatible material for tissue replacement. In this study, we used
      hydrogen peroxide to control the pore size and fibre crossing density of the ESM.
      Structural and chemical properties were investigated using AFM, optical
      microscopy, contact angle, and FTIR. We show that the structure and permeability
      of the ESM can be controlled by timed exposure to H2O2 and we demonstrate this
      effect using red blood cells. This process provides a simple method for preparing
      biocompatible membranes, with controlled selectivity for biofiltration
      applications. 

PMID- 23870937
TI  - Changes on indigenous microbiota, colour, bioactive compounds and antioxidant
      activity of pasteurised pomegranate juice.
AB  - Juices prepared from arils of 'Mollar' pomegranates were analysed for naturally
      occurring microorganisms, CIE Lab colour parameters, total phenols, anthocyanins
      and punicalagins, ellagic acid content and antioxidant capacity before and after
      low-, mild- and high-temperature pasteurisations (LTPs, MTPs and HTPs): 65, 80
      and 90  degrees C for 30 or 60s. Mean aerobic plate count (APC), yeast and mold
      count (YMC), and lactic acid bacteria (LAB) for fresh juices were 5.7, 5.36 and
      4.0 log CFU/mL, respectively. MTPs and HTPs were sufficiently effective to
      decrease APCs to nil or negligible levels. An increase in CIE a values and
      decrease in CIE b values were the characteristic colour changes in heat-treated
      juices. The effect of pasteurisations showed that total phenols, punicalagins and
      ellagic acid were not much affected by thermal processing. Total anthocyanin
      content and antioxidant capacity were substantially and significantly influenced
      by the heat treatment applied. A linear relationship was observed between Trolox
      equivalent antioxidant capacity (TEAC) values and total anthocyanins, suggesting
      that they contributed strongly to the antioxidant capacity of pomegranate juice.

PMID- 23870938
TI  - Assessment of DNA degradation induced by thermal and UV radiation processing:
      implications for quantification of genetically modified organisms.
AB  - DNA quality is an important parameter for the detection and quantification of
      genetically modified organisms (GMO's) using the polymerase chain reaction (PCR).
      Food processing leads to degradation of DNA, which may impair GMO detection and
      quantification. This study evaluated the effect of various processing treatments
      such as heating, baking, microwaving, autoclaving and ultraviolet (UV)
      irradiation on the relative transgenic content of MON 810 maize using pRSETMON
      02, a dual target plasmid as a model system. Amongst all the processing
      treatments examined, autoclaving and UV irradiation resulted in the least
      recovery of the transgenic (CaMV 35S promoter) and taxon-specific (zein) target
      DNA sequences. Although a profound impact on DNA degradation was seen during the
      processing, DNA could still be reliably quantified by Real-time PCR. The measured
      mean DNA copy number ratios of the processed samples were in agreement with the
      expected values. Our study confirms the premise that the final analytical value
      assigned to a particular sample is independent of the degree of DNA degradation
      since the transgenic and the taxon-specific target sequences possessing
      approximately similar lengths degrade in parallel. The results of our study
      demonstrate that food processing does not alter the relative quantification of
      the transgenic content provided the quantitative assays target shorter amplicons
      and the difference in the amplicon size between the transgenic and taxon-specific
      genes is minimal. 

PMID- 23870939
TI  - A NMR metabolomics study of the ripening process of the Fiore Sardo cheese
      produced with autochthonous adjunct cultures.
AB  - Fiore Sardo (FS) is a traditional Italian raw ewe's milk cheese carrying a
      Protected Designation of Origin (PDO). This study investigated the kinetics of FS
      cheese ripening by physicochemical parameters, microbial counting, and NMR
      metabolomics using aqueous extracts. Four Fiore Sardo cheeses, manufactured from
      milk with deliberately added autochthonous lactic acid bacteria (LAB) or
      commercial starters were studied during a period of 90days of ripening. Major
      differences in the metabolic profiles were observed amongst the samples as a
      function of the adjunct culture utilised. (1)H NMR metabolomics in combination
      with multivariate data analysis was able to classify cheese samples on the basis
      of their maturation age and the type of added cultures. These findings lay the
      metabolic basis for the authentication of Fiore Sardo cheese produced in
      compliance with PDO specifications which allow the use of only native LAB
      cultures. 

PMID- 23870940
TI  - Characterization of wines according the geographical origin by analysis of
      isotopes and minerals and the influence of harvest on the isotope values.
AB  - We studied Brazilian wines produced by microvinification from Cabernet Sauvignon
      and Merlot grapes, vintages 2007 and 2008, from the Serra Gaucha, Campanha and
      Serra do Sudeste regions, in order to differentiate them according to
      geographical origin by using isotope and mineral element analyses. In addition,
      the influence of vintage production in isotope values was verified. Isotope
      analysis was performed by isotope ratio mass spectrometry (IRMS), and the
      determination of minerals was by flame atomic absorption (FAA). The best
      parameters to classify the wines in the 2008 vintage were Rb and Li. The results
      of the delta(13)C of wine ethanol, Rb and Li showed a significant difference
      between the varieties regardless of the region studied. The delta(18)O values of
      water and delta(13)C of ethanol showed significant differences, regardless of the
      variety. Discriminant analysis of isotope and minerals values allowed to classify
      approximately 80% of the wines from the three regions studied. 

PMID- 23870941
TI  - Inductively coupled plasma orthogonal acceleration time-of-flight mass
      spectrometry (ICP-oa-TOF-MS) analysis of heavy metal content in Indocalamus
      tesselatus samples.
AB  - Indocalamus tesselatus is one of the most popular packing materials in China.
      Heavy metals in Chinese I. tesselatus samples have received great interest
      because they are related to health. A simple and fast method for the
      determination of Pb, Cd, Mn, Ni, Cr, As, Hg, Cu and Zn, by inductively coupled
      plasma orthogonal acceleration time-of-flight mass spectrometry (ICP-oa-TOF-MS),
      following microwave closed vessel digestion of samples, was proposed. The method
      was validated using standard reference material (GBW 07605-Tea). Samples of I.
      tesselatus from five different regions of China were analysed using the proposed
      method. Heavy metals contents from different regions were found at different
      levels. Their low contents of heavy metals showed that collection areas were not
      polluted and all collected I. tesselatus samples could be unreservedly used as
      food packing materials without any health risk. 

PMID- 23870942
TI  - Determination of As, Cd, Hg and Pb in herbs using slurry sampling electrothermal
      vaporisation inductively coupled plasma mass spectrometry.
AB  - Inductively coupled plasma mass spectrometry coupled with ultrasonic slurry
      sampling electrothermal vaporisation (USS-ETV-ICP-MS) has been applied to
      determine As, Cd, Hg and Pb in 0.5% m/v slurries of several herb samples. 1% m/v
      8-Hydroxyquinoline was used as the modifier to enhance the ion signals. The
      influences of instrument operating conditions, slurry preparation and
      interferences on the ion signals were reported. This method has been applied to
      the determination of As, Cd, Hg and Pb in NIST SRM 1547 peach leaves and SRM
      1573a tomato leaves reference materials and three herb samples purchased from the
      local market and ground to 150 MUm. The analysis results of the standard
      reference materials agreed with the certified values which are at sub MUg g(-1)
      levels. Precision between sample replicates was better than 4% for all the
      determinations. The method detection limits estimated from standard addition
      curves were about 0.3, 0.1, 0.1 and 0.2 ng g(-1) for As, Cd, Hg and Pb,
      respectively, in original herb samples.

PMID- 23870943
TI  - Determination of amino acid contents of manketti seeds (Schinziophyton
      rautanenii) by pre-column derivatisation with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate and RP-HPLC.
AB  - Defatted kernel flour from manketti seed kernels (Schinziophyton rautanenii) is
      an underutilised natural product. The plant grows in the wild, on sandy soils
      little used for agriculture in Southern Africa. The kernels are rich in protein
      and have a great potential for improving nutrition. The protein content and amino
      acid profile of manketti seed kernel were studied, using a new analytical method,
      in order to evaluate the nutritional value. The crude protein content of the
      press cake and defatted kernel flour was 29.0% and 67.5%, respectively. Leucine
      and arginine were found to be the most abundant essential and non-essential amino
      acids, respectively. The seed kernel contained 4.77 g leucine and 12.34 g
      arginine/100 g of defatted seed kernel flour. Methionine and proline were the
      least abundant essential and non-essential amino acids to with 0.23 g methionine
      and 0.36 g proline/100 g of defatted seed kernel flour, respectively. Validation
      of the pre-column derivatisation procedure with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate (AQC) for the determination of amino acids was
      carried out. The analytical parameters were determined: linearity (0.0025-0.20
      mM), accuracy of the derivatisation procedure: 86.7-109.8%, precision (method:
      0.72-5.04%, instrumental: 0.14-1.88% and derivatisation: 0.15-2.94% and 0.41
      4.32% for intraday and interday, respectively). Limits of detection and
      quantification were 6.80-157 mg/100 g and 22.7-523 mg/100 g kernel flour,
      respectively.

PMID- 23870944
TI  - The alpha-amylase and alpha-glucosidase inhibitory effects of Irish seaweed
      extracts.
AB  - To date, numerous studies have reported on the antidiabetic properties of various
      plant extracts through inhibition of carbohydrate-hydrolysing enzymes. The
      objective of this research was to evaluate extracts of seaweeds for alpha-amylase
      and alpha-glucosidase inhibitory effects. Cold water and ethanol extracts of 15
      seaweeds were initially screened and from this, five brown seaweed species were
      chosen. The cold water and ethanol extracts of Ascophyllum nodosum had the
      strongest alpha-amylase inhibitory effect with IC50 values of 53.6 and 44.7
      MUg/ml, respectively. Moreover, the extracts of Fucus vesiculosus Linnaeus were
      found to be potent inhibitors of alpha-glucosidase with IC50 values of 0.32 and
      0.49 MUg/ml. The observed effects were associated with the phenolic content and
      antioxidant activity of the extracts, and the concentrations used were below
      cytotoxic levels. Overall, our findings suggest that brown seaweed extracts may
      limit the release of simple sugars from the gut and thereby alleviate
      postprandial hyperglycaemia.

PMID- 23870945
TI  - Biologically active peptides obtained by enzymatic hydrolysis of Adzuki bean
      seeds.
AB  - This study investigated the antioxidant and antihypertensive activities of
      peptides obtained from protein fractions of Adzuki bean seeds. Peptides were
      obtained by the use of hydrolytic enzymes in vitro under gastrointestinal
      conditions. A determination was made of the activity of the peptide inhibitors of
      the angiotensin I converting enzyme (ACE), and the antiradical and ion chelating
      activity of peptides from different protein fractions. The highest peptide levels
      after the absorption process (<7 kDa) were noted in the albumin fraction (50.69
      MUg/ml). Furthermore, it was found that peptides from the prolamin fraction were
      characterised by the highest antiradical activity and ACE inhibitory activity
      (IC50=0.17 mg/ml). Peptides obtained from the globulin fraction showed the
      highest ability to chelate iron ions, and peptides from the glutelin fraction
      were characterised as being the most effective in the chelation of copper ions.

PMID- 23870946
TI  - Application of the differential colorimetry and polyphenolic profile to the
      evaluation of the chromatic quality of Tempranillo red wines elaborated in warm
      climate. Influence of the presence of oak wood chips during fermentation.
AB  - The effect of adding American oak wood chips during fermentation on Tempranillo
      red wines elaborates in a warm climate has been studied. Our attention was
      focused on the tristimulus colorimetry, differential colorimetry and phenolic
      compounds related to wine colour. This technique was applied as an oenological
      alternative to the conventional winemaking for avoiding the common fall of colour
      of red wines elaborated in warm climates. The addition of oak wood chips promoted
      the colour enhancement and stabilisation, producing wines with a notably darker
      colour and with more bluish tonality. This fact was also related to the
      significantly higher content of some phenolic compounds. On the basis of the
      results, it could be affirmed that the addition of oak wood chips during
      fermentation induced visually perceptible colour changes (by the analysis of
      DeltaEab(*), %Delta(2)L, %Delta(2)C and %Delta(2)H), mainly in a quantitative
      way, and also a lower percentage of diminution of colour.

PMID- 23870947
TI  - Authentication of Alicante's Mountain cherries protected designation of origin by
      their mineral profile.
AB  - Chemometric analysis of inductively coupled plasma optical emission spectroscopy
      (ICP-OES) data was employed to verify the origin of cherry samples of different
      areas of Spain: Aragon, Caceres, Castellon, Huesca and Alicante's Mountain
      Protected Geographic Indication (PGI). The ability of multivariate analysis
      methods, such as discriminant analysis (DA), was used to achieve cherry
      classification from their mineral content. The study was performed using 22
      variables (concentrations of Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, K,
      Mg, Mn, Na, Ni, Pb, Se, Sr, Ti and Te) and 23 variables (concentrations of Al,
      As, B, Ba, Be, Bi, Ca, Cd, Cr, Cu, Fe, K, Li, Mg, Mo, Na, Ni, Pb, Se, Sr, Ti, Tl
      and V), for cherry stone and edible part, respectively, and the best
      discrimination was found on using edible part mineral composition which permits a
      correct classification of 100% of the considered samples. 

PMID- 23870948
TI  - Effects of Salvia officinalis and Thymus vulgaris on oxidant-induced DNA damage
      and antioxidant status in HepG2 cells.
AB  - Salvia officinalis (SO) and Thymus vulgaris (TV) are medicinal plants well known
      for their curative powers. However, the molecular mechanisms responsible for
      these abilities of sage and thyme have not been fully understood yet. In this
      study we investigated the composition and the quantitative estimation of plant
      extracts, the protective effects of plant extracts against hydrogen peroxide- and
      2,3-dimethoxy-1,4-naphthoquinone-induced DNA damage, and levels of enzymatic and
      non-enzymatic antioxidants (superoxide dismutase, glutathione peroxidase,
      glutathione) in human HepG2 cells. To measure antioxidative activity of plant
      extracts we used three assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric
      reducing antioxidant power (FRAP) and 2,2'-azinobis(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS). The results showed that the oxidant-induced DNA lesions
      were significantly reduced in cells pre-treated with the plant extracts studied.
      The observed DNA-protective activity could be explained by both elevation of GPx
      activity in cells pre-treated with SO and TV and antioxidant activity of SO and
      TV. 

PMID- 23870949
TI  - Determination of safranine T in food samples by CTAB sensitised fluorescence
      quenching method of the derivatives of calix[4]arene.
AB  - In this paper, the interaction of safranine T (ST) and calix[4]arene (4,10,16,22
      tetramethoxylresorcinarene carboxylic acid derivatives (TRCA)) was investigated
      with fluorescence spectroscopy. The results was shown that the fluorescence
      intensity of TRCA could be quenched by ST, and the fluorescence quenching
      (DeltaF=FTRCA-FST-TRCA) was sensitised in cetyltrimethyl ammonium bromide (CTAB).
      Under the optimal conditions, the linear range of calibration curve for the
      determination of ST was 0.10-4.00 MUg/mL. The detection limit and RSD was 0.034
      MUg/mL, 2.30% (n=3). The quantum yield (Yu) of ST was approximately 2.0 times
      higher in the presence of CTAB than that in the absence of CTAB. The method has
      been applied for the determination of ST in food samples with satisfactory
      results.

PMID- 23870950
TI  - Variation of active constituents and antioxidant activity in pyrola [P. incarnata
      Fisch.] from different sites in Northeast China.
AB  - The variation of antioxidant activity and active components in pyrola [Passiflora
      incarnata Fisch.] from eight sites in Northeast China were investigated. Total
      phenolic and flavonoid contents were determined and varied within the range of
      39.66-181.48 mg/g and 2.47-22.11 mg/g, respectively. Antioxidant activities were
      determined by scavenging activity against DPPH and ABTS, by a reducing power test
      and by a beta-carotene-linoleic acid bleaching test. The IC50 of Tahe samples
      determined by the DPPH test was 0.106+/-0.006 mg/mL which was very close to that
      of Vc (0.076+/-0.004 mg/mL). The Tahe samples had good antioxidant activity.
      Principal component activity analysis indicated that the Tahe samples of P.
      incarnata had the highest potential antioxidant properties, and may be a valuable
      antioxidant natural resource in the northeast of China.

PMID- 23870951
TI  - Lipase-catalysed interesterification between canola oil and fully hydrogenated
      canola oil in contact with supercritical carbon dioxide.
AB  - The processing parameters in enzymatic reactions using CO2-expanded (CX) lipids
      have strong effects on the physical properties of liquid phase, degree of
      interesterification, and physicochemical properties of the final reaction
      products. CX-canola oil and fully hydrogenated canola oil (FHCO) were
      interesterified using Lipozyme TL IM in a high pressure stirred batch reactor.
      The effects of immobilised enzyme load, pressure, substrate ratio and reaction
      time on the formation of mixed triacylglycerols (TG) from trisaturated and
      triunsaturated TG were investigated. The optimal immobilised enzyme load,
      pressure, substrate ratio and time for the degree of interesterification to reach
      the highest equilibrium state were 6% (w/v) of initial substrates, 10 MPa, blend
      with 30% (w/w) of FHCO and 2h, respectively. The physicochemical properties of
      the initial blend and interesterified products with different FHCO ratios
      obtained at optimal reaction conditions were determined in terms of TG
      composition, thermal behaviour and solid fat content (SFC). The amounts of
      saturated and triunsaturated TG decreased while the amounts of mixed TG increased
      as a result of interesterification. Thus, the interesterified product had a lower
      melting point, and broader melting and plasticity ranges compared to the initial
      blends. These findings are important for better understanding of CX-lipid
      reactions and for optimal formulation of base-stocks of margarine and
      confectionary fats to meet industry demands.

PMID- 23870952
TI  - Activated effect of lignin on alpha-amylase.
AB  - This paper reports a new kind of activator of alpha-amylase, lignin, which can
      greatly increase alpha-amylase activity. The promoted ratio of lignin is even
      much higher than that of chloride ion, the traditional activator of alpha
      amylase. Further experimental results reveal that lignin may interact with alpha
      amylase to form a 1:1 complex with a binding constant of 4.47*10(5) M(-1). The
      binding is spontaneous and lignin/alpha-amylase complex formation is an
      exothermal reaction. Hydrogen bonding plays a key role and non-radiation energy
      transfers from alpha-amylase to lignin in the binding process. Lignin, combining
      with alpha-amylase, conforms to a first-order exponential decay function. The
      formation of the lignin/alpha-amylase complex results in the reduction of alpha
      helical content from 57.7% to 53.9%, the increase of the polarity around
      tryptophan residues, the decrease of the hydrophobicity, and the enlargement of
      protein granule volume. This work will give a deeper insight into lignin as a
      kind of dietary fibre, known as an important food functional factor. Furthermore,
      it also contributes to the exploration of an activator of alpha-amylase, used in
      the food industry.

PMID- 23870953
TI  - Centrifugal partition chromatography applied to the isolation of oak wood aroma
      precursors.
AB  - Flavours extracted from oak wood during barrel ageing contribute to the
      organoleptic character of wines and spirits. The aim of this work was to identify
      the glycosidic precursors of the key volatile compounds responsible for oak wood
      aroma. Oak extract is a very complex matrix and, furthermore, precursors are
      present in very small quantities. Preparative centrifugal partition
      chromatography (CPC) is a promising solution for purifying the oak extract. The
      solvent system was selected on the basis of the partition coefficient of
      glycosidase enzyme activity (Kca). Thanks to the efficacy of CPC separation,
      three glucoside gallates were subsequently isolated by HPLC chromatography.
      Vanillin-(6'-O-galloyl)-O-beta-D-glucopyranoside, 3,4,5-trimethoxyphenyl-(6'-O
      galloyl)-O-beta-D-glucopyranoside, and (6R,9R)-3-oxo-alpha-ionol-9-O-(6'-O
      galloyl)-beta-glucopyranoside (macarangioside E) were isolated and identified.
      This was the first time that vanillin-(6'-O-galloyl)-O-beta-D-glucopyranoside was
      identified and the first time that macarangioside E was isolated from oak wood.
      Heating macarangioside E resulted in the formation of megastigmatrienone, which
      has an aroma reminiscent of tobacco.

PMID- 23870954
TI  - Monitoring dry-curing of S. Daniele ham by magnetic resonance imaging.
AB  - S. Daniele hams were collected at different stages during dry-curing and
      submitted to magnetic resonance imaging (MRI) according to the acquisition Spin
      Echo sequences T1 and T2. The intensity of the MR signals in the images of the
      Semimembranosus, Semitendinosus, Rectus femoris and Biceps femoris muscles of the
      hams was computed and expressed in grey levels. Muscles were also submitted to
      traditional analyses, including aw, soluble solids, sodium chloride, total and
      water soluble nitrogen. T1 and T2 MR signals well described the evolution of the
      phenomena occurring in the different muscles during dry-curing. MR signal
      acquired in T2 mode well correlated with traditional indicators in
      Semitendinosus, Rectus femoris and Biceps femoris muscles. Predictive models
      estimating the value of aw, moisture, salt content and proteolysis extent on the
      basis of the MR signal intensity were proposed. 

PMID- 23870955
TI  - Dietary flavonoids fisetin, luteolin and their derived compounds inhibit
      arginase, a central enzyme in Leishmania (Leishmania) amazonensis infection.
AB  - Fisetin, quercetin, luteolin and 7,8-hydroxyflavone show high activity in
      Leishmania cultures and present low toxicity to mammalian cells. In this work,
      the structural aspects of 13 flavonoids were analyzed for their inhibition of the
      arginase enzyme from Leishmania (Leishmania) amazonensis. A higher potency of
      arginase inhibition was observed with fisetin, which was four and ten times
      greater than that of quercetin and luteolin, respectively. These data show that
      the hydroxyl group at position 3 contributed significantly to the inhibitory
      activity of arginase, while the hydroxyl group at position 5 did not. The absence
      of the catechol group on apigenin drastically decreased arginase inhibition.
      Additionally, the docking of compounds showed that the inhibitors interact with
      amino acids involved in the Mn(+2)-Mn(+2) metal bridge formation at the catalytic
      site. Due to the low IC50 values of these flavonoids, they may be used as a food
      supplement in leishmaniasis treatment. 

PMID- 23870956
TI  - Dispersive liquid-liquid microextraction for the determination of copper in
      cereals and vegetable food samples using flame atomic absorption spectrometry.
AB  - Dispersive liquid-liquid microextraction (DLLME) is applied for the determination
      of copper in cereals and vegetable food samples using flame atomic absorption
      spectrometry (FAAS). The maximum extraction efficiency of copper was obtained
      after the optimisation of parameters such as extraction and dispersing solvents,
      pH, concentration of 2,9-dimethyl-1,10-phenanothroline (DPT), N-phenylbenzimidoyl
      thiourea (PBITU) and salt. The optimised methodology exhibited a good linearity
      in the range of 0.2-20 ng/mL copper with relative standard deviations percentage
      (RSD,%) from +/-1.5% to 3.5%. The method is found to be simple and rapid for the
      analysis of copper in food samples with the limit of detection (LOD) and
      quantitation (LOQ) were 0.05 and 0.16 ng/mL, respectively. Good recoveries of
      copper were obtained in the range of 93.5-98.0% in food samples as well as in
      Certified Reference Material (99.1%). The application of the proposed method has
      been successfully tested for the determination of copper in cereals (maize,
      millet, rice, wheat, gram, lentils, kidney beans and green beans) and vegetable
      (potato, cauliflower, tomato, spinach, green beans, lettuce, egg plants and
      bitter gourd) food samples.

PMID- 23870957
TI  - Extensive characterisation of bioactive phenolic constituents from globe
      artichoke (Cynara scolymus L.) by HPLC-DAD-ESI-QTOF-MS.
AB  - The aim of this work was to characterise the phenolic compounds in artichoke
      (hearts) by using HPLC coupled to DAD-ESI-QTOF-MS, which proved useful in
      characterising 61 phenolic and other polar compounds. Notably, of the 61
      compounds characterised, 34 new phenolic compounds with their isomers have been
      tentatively characterised in artichoke for the first time, namely: 3
      hydroxybenzoic acids, 17 hydroxycinnamic acids, 4 lignans, 7 flavones, 2
      flavonols, and 1 phenol derivative. Moreover, a total of 28 isomers of previously
      described phenolics have also been detected. The data compiled from the
      qualitative polyphenol characterisation indicate that the artichoke extract
      analysed (Blanca de Tudela variety) could be regarded as a bioactive functional
      food and also as a promising source of antioxidant phenolic compounds.

PMID- 23870958
TI  - Interaction of anthocyanins with human serum albumin: influence of pH and
      chemical structure on binding.
AB  - The affinity of anthocyanins for human serum albumin (HSA) was determined by a
      fluorescence quenching method. The effects of pH and structure of anthocyanins on
      the binding constants were studied. The constants for binding of anthocyanins to
      HSA ranged from 1.08*10(5) to 13.2*10(5) M(-1). A hydrophobic effect at acidic pH
      was shown by the relatively high positive entropy values under the conditions
      studied. Electrostatic interactions, including hydrogen bonding, contributed to
      the binding at pH 7.4. The effect of structure of anthocyanins on the affinity
      was pH-dependent, particularly the effect of additional hydroxyl substituents.
      Hydroxyl substituents and glycosylation of anthocyanins decreased the affinity
      for binding to HSA at lower pH (especially pH 4), but increased the strength of
      binding at pH 7.4. In contrast, methylation of a hydroxyl group enhanced the
      binding at acidic pH, whilst this substitution reduced the strength of binding at
      pH 7.4. This paper shows that changes in anthocyanin structure or reductions in
      pH, which may occur in the region of inflammatory sites, have an effect on the
      binding of anthocyanins to HSA.

PMID- 23870959
TI  - Oxidative stability of soybean oil in oleosomes as affected by pH and iron.
AB  - The oxidative stability of oil in soybean oleosomes, isolated using the Enzyme
      Assisted Aqueous Extraction Process (EAEP), was evaluated. The effects of ferric
      chloride, at two concentration levels (100 and 500 MUM), on lipid oxidation, was
      examined under pH 2 and 7. The peroxide value (PV) and thiobarbituric acid
      reactive substance (TBARS) value of oil, in oleosome suspensions stored at 60 
      degrees C, were measured over a 12 day period. The presence of ferric chloride
      significantly (P<0.05) affected the oxidative stability of oil in the isolated
      oleosome, as measured by the PV and TBARS. Greater lipid oxidation occurred under
      an acidic pH. In the pH 7 samples, the positively charged transition metals were
      strongly attracted to the negatively charged droplets. However, the low zeta
      potential and the high creaming rate at this pH, may have limited the oxidation.
      Freezing, freeze-drying or heating of oleosomes have an insignificant impact on
      the oxidative stability of oil in isolated soybean oleosomes. Manufacturers
      should be cautious when adding oleosomes as ingredients in food systems
      containing transition metal ions.

PMID- 23870960
TI  - Rapid method for quantification of nine sulfonamides in bovine milk using
      HPLC/MS/MS and without using SPE.
AB  - Sulfonamides are antimicrobial agents widely employed in animal production and
      their residues in food could be an important risk to human health. In the dairy
      industry, large quantities of milk are monitored daily for the presence of
      sulfonamides. A simple and low-cost extraction protocol followed by a liquid
      chromatographic-tandem mass spectrometry method was developed for the
      simultaneous detection of nine sulfonamides in whole milk. The method was
      validated at the maximum residue limits established by European legislation. The
      limits of quantification obtained for most sulfonamides were between 12.5 and 25
      MUg kg(-1), detection capabilities ranged from 116 to 145 MUg kg(-1), and
      recoveries, at 100 MUg kg(-1), were greater than 89+/-12.5%. The method was
      employed to analyse 100 raw whole bovine milk samples collected from dairy farms
      in the northwest region of Spain. All of the samples were found to be compliant,
      but two were positive; one for sulfadiazine and the other for
      sulfamethoxipyridazine.

PMID- 23870961
TI  - Rapid analysis of avenacosides in grain and husks of oats by UPLC-TQ-MS.
AB  - Avenacosides A (AA) and B (AB) as well as 26-desglucoavenacoside A (26dAA) were
      quantified in oats using rapid and sensitive method utilising UPLC-TQ-MS. In the
      grain, AA and AB were revealed as the primary saponins, whereas in the husks, dAA
      was predominant. Inconsistent with the published data, observed concentrations of
      AA and AB in the grain were very similar. Presumably, this is due to higher
      sensitivity and better selectivity of the mass spectrometry-based quantification
      method, thus allowing for more precise measurements. Elevated level of an active
      fungicidal form of saponin, dAA in the husks possibly indicates they are more
      prone to fungal attacks. 

PMID- 23870962
TI  - Complexes between linoleate and native or aggregated beta-lactoglobulin:
      interaction parameters and in vitro cytotoxic effect.
AB  - The dairy protein beta-lactoglobulin (betalg) is known to form a complex with
      fatty acids (FA). Due to industrial processing, betalg is often in its non-native
      form in food products, which can modify the FA/betalg complex properties. We
      investigated the interaction of bovine betalg, in selected structural forms
      (native betalg, a covalent dimer and as nanoparticles), with linoleate (C18:2).
      Using fluorescence and Isothermal Titration Calorimetry, linoleate was found to
      bind betalg at two different binding sites. Regardless of the structural state of
      betalg, association constants remained in the same order of magnitude. However,
      the stoichiometry increased up to 6-fold for nanoparticles, compared to that of
      native betalg. The impact of these structural changes on linoleate uptake in
      vitro was measured by cytotoxicity assays on Caco-2 cells. The order of
      cytotoxicity of linoleate was as follows: free>complexed to dimers>complexed to
      nanoparticles>complexed to native betalg. Therefore, the in vitro cytotoxicity of
      linoleate could be modulated by altering the state of betalg aggregation, which
      in turn affects its binding capacity to the FA. 

PMID- 23870963
TI  - Intracellular proteins of ethanol-treated yeast cells involved in iron sorption.
AB  - Iron is essential for human health, but it sometimes causes an unpleasant taste,
      rusty colour and a decrease in the stability of food products. Previously, we
      found that ethanol-treated yeast (ETY) cells could remove iron from wine and
      juice, and reduce the fishy aftertaste induced by iron in wine-seafood pairings.
      However, the mechanism of iron sorption by ETY cells is undefined; thus, there is
      no indicator that can be used to estimate the iron sorption capacity of these
      cells. In this study, we showed that cell wall components are not mainly
      associated with iron sorption by investigating ETY cells with the cell wall
      removed. Moreover, plasma membrane permeability was correlated with the iron
      sorbing capacity of the cells. Microscopic analysis showed that iron accumulated
      within ETY cells. Proteinase-treated ETY cells had no iron sorbing capacity. On
      the basis of these results, we conclude that intracellular proteins are involved
      in iron sorption by ETY cells. 

PMID- 23870964
TI  - Temporal trends of PCBs in feed and dietary influence in farmed rainbow trout
      (Oncorhynchus mykiss).
AB  - As a rainbow trout producer, Italy is accounted as fifth in the world and second
      in continental Europe. In this study, the levels of the eighteen PCBs in feed and
      in trout, showed a statistical significant difference (p<0.01) throughout the
      years, with a declining trend from 2005 to 2010. This trend shows effectively
      that quality and safety of trout feeds has greatly improved during the last years
      and, as a consequence, also the PCBs values in muscle trout, showed a decreasing
      trend. Moreover, feed Sigma18PCBs showed a statistical significant difference
      (p<0.01) among the analysed brands and was positively correlated (p<0.01 and
      r=0.451) with the rainbow trout muscle Sigma18PCBs. These results showed that the
      presence of PCBs in trout muscle is directly linked to the chemical quality of
      aquaculture feed. The most commonly detected PCBs congeners were congeners PCB
      153 and PCB 138 in all the three compared brands. 

PMID- 23870965
TI  - Comprehensive assay of flavanones in citrus juices and beverages by UHPLC-ESI
      MS/MS and derivatization chemistry.
AB  - Flavanones, a class of flavonoids present in large amounts in fruits and
      vegetables, have been assayed by LC-MS/MS and derivatization chemistry using
      d0/d3-labelled derivatized internal standards obtained by simple reaction
      procedures which involves d0/d3 methoxyamine. The assay method considers 13
      flavanones including aglycones, neohesperidosides, rutinosides and 3-hydroxy-3
      methyl glutaryl derivatives. The strengths of the method consist in a relative
      short analysis time (16 min) and good repeatability and reproducibility values
      which are in most cases under 10% (RSD%). The accuracy values range from 95.4% to
      111.3% whilst the LOQ values ranges from 0.05 to 0.29 mg/L depending on the
      analyte.

PMID- 23870966
TI  - Whey protein isolate polydispersity affects enzymatic hydrolysis outcomes.
AB  - The effects of heat-induced denaturation of whey protein isolate (WPI) on the
      enzymatic breakdown of alpha-La, caseinomacropeptide (CMP), beta-Lg A and beta-Lg
      B were observed as hydrolysis proceeded to a 5% degree of hydrolysis (DH) in both
      unheated and heat-treated (80  degrees C, 10 min) WPI dispersions (100 g L(-1)).
      Hydrolysis of denatured WPI favoured the generation of higher levels of free
      essential amino acids; lysine, phenylalanine and arginine compared to the
      unheated substrate. LC-MS/MS identified 23 distinct peptides which were
      identified in the denatured WPI hydrolysate - the majority of which were derived
      from beta-Lg. The mapping of the detected regions in alpha-La, beta-Lg, and CMP
      enabled specific cleavage points to be associated with certain serine endo
      protease activities. The outcomes of the study emphasise how a combined approach
      of substrate heat pre-treatment and enzymology may be used to influence
      proteolysis with attendant opportunities for targeting unique peptide production
      and amino acid release.

PMID- 23870967
TI  - Effect of pretreatment on enzymatic hydrolysis of bovine collagen and formation
      of ACE-inhibitory peptides.
AB  - Bovine collagen was pre-treated (boiled or high pressure (HP)-treated) and then
      hydrolysed by 6 proteases. The degree of hydrolysis (DH) and the angiotensin
      converting enzyme (ACE)-inhibitory activity of hydrolysates were measured. All
      enzymes used were able to partly degrade collagen and release ACE-inhibitory
      peptides. The highest ACE-inhibitory activity was obtained with Alcalase.
      Pretreatment significantly influenced the DH and ACE-inhibition. For most
      enzymes, boiling for 5 min resulted in a significantly higher DH and ACE
      inhibitory activity. With Alcalase and collagenase, hydrolysis and release of ACE
      inhibitory peptides occurred without any pretreatment, but HP-treatment
      significantly improved the DH and ACE-inhibitory activity. HP did not markedly
      affect the hydrolysis with the other enzymes. The major peptides obtained with
      Alcalase were identified; all were released from the triple helix structure of
      collagen. Many of these peptides had C-terminal sequences similar to known ACE
      inhibitory peptides. The present results suggest that collagen-rich food
      materials are good substrates for the release of potent ACE-inhibitory peptides,
      when proper pre-treatment and enzymatic treatment is applied.

PMID- 23870968
TI  - Exposure or release of ferulic acid from wheat aleurone: impact on its
      antioxidant capacity.
AB  - The relationship between the aleurone cell integrity and the exposure or release
      of bioavailable ferulic acid (FA) with the antioxidant capacity of aleurone in in
      vitro and under simulated gastric conditions was explored. The antioxidant
      capacity of aleurone was increased by around 2-fold when its median particle size
      was reduced to under 50 MUm. The opening of aleurone cells increased the physical
      exposure of FA bound to the insoluble polysaccharides, which seemed to be
      responsible of the increased antioxidant capacity. Synergistic combination of
      xylanase and feruloyl esterase was found to be the most efficient enzymatic
      treatment releasing up to 86% of total FA in bioaccessible forms. This enzymatic
      treatment significantly enhanced the radical scavenging activity of aleurone by
      up to 4-fold, which overlapped the overall antioxidant potential estimated from
      the total content of FA in aleurone. The improvement in the antioxidant capacity
      of aleurone was also observed in the simulated gastric digestion by inhibition of
      lipid oxidation. 

PMID- 23870969
TI  - Prediction of the time evolution of pH in meat.
AB  - In this paper we compare experimental data on pH decline in carcasses and
      predictions using a model, based on earlier work of Vetharaniam and coworkers.
      This model is extended in order to cope with the varying temperatures in the
      slaughterhouse. We have measured initial glycogen, and the pH and temperature at
      multiple times in the production chain. We have obtained good comparison between
      model predictions and our measurements. Furthermore, the correlation between
      initial glycogen content and ultimate pH as predicted by the model, follows
      closely experimental data reported earlier in literature. Being able to predict
      pH decline and ultimate pH, one can obtain reliable indications of final meat
      quality. 

PMID- 23870970
TI  - Frying stability of high oleic sunflower oils as affected by composition of
      tocopherol isomers and linoleic acid content.
AB  - The influence of linoleic acid content and tocopherol isomeric composition on the
      frying performance of high oleic sunflower oil was evaluated during a 14-day
      restaurant style frying operation. At equal linoleic acid content, no significant
      difference was observed between high oleic sunflower oil containing only alpha
      tocopherol and the sample containing a mixture of alpha-, gamma-, and delta
      isomers as measured by the amount of total polar components, oligomers, anisidine
      value, and free fatty acids. On the contrary, at similar tocopherol isomeric
      composition, high oleic sunflower oil containing lower amount of linoleic acid
      showed superior frying stability compared to the sample with a higher content of
      linoleic acid, suggesting that the frying performance of high oleic sunflower oil
      is dictated primarily by the level of linoleic acid, with the tocopherol isomeric
      composition of the oil having no significant influence. In all oil samples, the
      loss of gamma-tocopherol was higher than the corresponding loss of alpha
      tocopherol. 

PMID- 23870971
TI  - In vitro hypoglycaemic and hypolipidemic potential of white tea polyphenols.
AB  - The leaves at different processing stages of a single tea cultivar in order to
      obtain white (WT), green (GT) and black tea (BT) samples, were analysed. The
      capacities of tea polyphenolics to influence the glucose and lipid metabolism in
      HepG2 cell lines were evaluated. WT appeared the most active in reducing the
      glucose and cholesterol uptake (+17.7% and +32.4% in the glucose and cholesterol
      cell medium concentration, respectively). Incubation with WT enhanced LDL
      receptor binding activity by 40% (+20% for GT and +0% for BT) and led to an
      increase in HDL cell medium concentration of 33.3% (+20% for GT and +0% for BT).
      Finally, WT revealed the best inhibition capacity against lipase activity, and
      triglyceride levels in the cell medium increased by 400% (+382.6% for GT and
      +191.3% for BT). The present study intended to contribute to the little knowledge
      about the potential health benefits of white tea in individuals affected by
      metabolic syndrome. 

PMID- 23870972
TI  - Generation of selenium-enriched rice with enhanced grain yield, selenium content
      and bioavailability through fertilisation with selenite.
AB  - To fulfill the natural human needs of selenium, selenium biofortification has
      been carried out in rice (Oryza sativa) in recent years. Despite some
      improvements have been made, the increase of selenium content in rice was still
      limited and a large amount of fertilisers are often required, which may cause
      environmental pullution. In this study, we further improved the selenium
      biofortification of rice by using less selenium fertilisers (10.5 g
      selenium/hectare) whereas, largely increasing selenium content in rice grains (up
      to 51 times vs. control). Furthermore, selenium speciation analysis, in vitro
      gastrointestinal digestion and antioxidant assays were performed to evaluate the
      selenium bioaccessibility and bioavailability in selenium-enriched rice grains.
      The major selenium species found were readily absorbable selenomethionine.
      Meanwhile, the selenium-enriched rice grains have significantly higher
      antioxidant bioactivities. In conclusion, this selenium-enriched rice has
      enormous potential for selenium supplementation in humans.

PMID- 23870973
TI  - Volatile compounds and bacterial community dynamics of chestnut-flour-based
      sourdoughs.
AB  - The aims of this study were the monitoring of the microbial dynamics by means of
      a polyphasic approach based on conventional isolation techniques and PCR-DGGE
      based methods in different chestnut-based sourdoughs and the evaluation of the
      impact of fermentation on volatile organic compounds formation during sourdoughs
      ripening. Members of the Lactobacillus plantarum group and Pediococcus
      pentosaceous dominated the sourdough ecosystems. Nevertheless, RAPD-PCR allowed
      recording a relevant genotypic biodiversity among strains coming from gluten-free
      flour combinations. Volatile compounds were characterised by GC/MS. A total of 59
      volatile compounds were identified, mainly alcohols, esters, acids, aldehydes and
      ketones. Principal component analysis of samples at the beginning and at the end
      of ripening offered a good separation of the samples and highlighted the effect
      of fermentation on the sensorial profile. 

PMID- 23870974
TI  - A modified ferrous oxidation-xylenol orange assay for lipoxygenase activity in
      rice grains.
AB  - Ferrous oxidation-xylenol orange assay reagent was reformulated by using spectral
      analysis of ferric-xylenol orange complex to detect low concentrations of
      lipoxygenase rice grain products. Reducing the levels of ferrous sulphate and
      xylenol orange in the FOX reagent enabled the detection of low concentrations of
      hydroperoxy fatty acid derived from lipoxygenase activity in the range of 0.1-1.5
      MUM. Protein, substrate and time courses of the modified FOX assay were studied
      to determine lipoxygenase activity in rice grain. The assay was also applicable
      as a high throughput technique for comparisons of lipoxygenase activity from
      various rice varieties. This has important implications for rapid screening for
      low-lipoxygenase containing rice cultivars in rice breeding program and grain
      quality during storage.

PMID- 23870975
TI  - Amino acids, fatty acids and sterols profile of some marine organisms from
      Portuguese waters.
AB  - Marine organisms have been increasingly regarded as good sources of new drugs for
      human therapeutics and also as nutrients for human diet. The amino acids, fatty
      acids and sterols profiles of the widely consumed echinoderms Paracentrotus
      lividus Lamarck (sea urchin), Holothuria forskali Chiaje (sea cucumber), the
      gastropod molluscs Aplysia fasciata Poiret and Aplysia punctata Cuvier (sea
      hares), from Portuguese waters, were established by GC-MS analysis. Overall, 10
      amino acids, 14 fatty acids and 4 sterols were determined. In general, all
      species presented the 10 amino acids identified, with the exceptions of H.
      forskali, in which no glycine, proline, trans-4-hydroxy-proline or phenylalanine
      were found, and of A. fasciata which did not contain proline. Unsaturated fatty
      acids were predominant compounds, with those from the omega-6 series, being in
      higher amounts than their omega-3 homologues, and cholesterol being the main
      sterol. The amino acids, fatty acids and sterols qualitative and quantitative
      composition of A. fasciata, A. punctata and H. forskali is reported here for the
      first time. 

PMID- 23870976
TI  - Effect of soybean processing on content and bioaccessibility of folate, vitamin
      B12 and isoflavones in tofu and tempe.
AB  - PURPOSE: To compare the content of bioaccessible folate, vitamin B12, and
      isoflavones in tofu and tempe, as influenced by soybean variety and food
      processing, particularly fermentation. PRINCIPAL RESULTS: Raw soybeans contained
      2207-2671 MUg/kg (dry matter) folate, cooked tempe 1493-4143, and cooked tofu 968
      1273 MUg/kg, the difference was attributed to the fermentation in tempe. Vitamin
      B12 was detected only in tempe (0.16-0.72 MUg/kg). Isoflavone aglycones were
      formed during soaking of soybeans, with only minor differences between the
      contents in cooked tempe (average 1922-2968 MUg/kg) or tofu (1667-2782 MUg/kg)
      but strongly depending on bean variety. CONCLUSIONS: Folate and vitamin B12
      contents were mainly influenced by microbial activity during fermentation,
      whereas isoflavone aglycone content was determined by bean variety. Tofu had
      lower folate and vitamin B12, but equal isoflavone contents as tempe.
      Bioaccessibility of folate (80-100%) and isoflavone aglycones (100%) were high.

PMID- 23870977
TI  - Development of sample preparation method for eleutheroside B and E analysis in
      Acanthopanax senticosus by ionic liquids-ultrasound based extraction and high
      performance liquid chromatography detection.
AB  - An ionic liquids-based ultrasonic-assisted extraction (ILUAE) method was
      successfully developed for extracting eleutheroside B and E from Radix
      Acanthopanax senticosus. Thirteen 1-alkyl-3-methylimidazolium ionic liquids with
      different cations and anions were investigated and 1-butyl-3-methylimidazolium
      bromide ([C4mim]Br) solution was selected as the solvent. The conditions for
      ILUAE, including the ionic liquid concentration, soaking time, ultrasonic power,
      ultrasonic time, solid-liquid ratio and number of extraction cycles, were
      optimized. With the proposed method, the energy consumption time was reduced to
      30 min, whereas conventional method requires about 4h. The proposed method had
      good recovery (97.96-103.39%) and reproducibility (RSD, n=5; 3.3% for
      eleutheroside B, 4.6% for eleutheroside E). ILUAE was an efficient, rapid and
      simple sample preparation technique that showed high reproducibility and was
      environmental friendly.

PMID- 23870978
TI  - Rapid analysis of adulterations in Chinese lotus root powder (LRP) by near
      infrared (NIR) spectroscopy coupled with chemometric class modeling techniques.
AB  - This paper develops a rapid analysis method for adulteration identification of a
      popular traditional Chinese food, lotus root powder (LRP), by near-infrared
      spectroscopy and chemometrics. 85 pure LRP samples were collected from 7 main
      lotus producing areas of China to include most if not all of the significant
      variations likely to be encountered in unknown authentic materials. To evaluate
      the model specificity, 80 adulterated LRP samples prepared by blending pure LRP
      with different levels of four cheaper and commonly used starches were measured
      and predicted. For multivariate quality models, two class modeling methods, the
      traditional soft independent modeling of class analogy (SIMCA) and a recently
      proposed partial least squares class model (PLSCM) were used. Different data
      preprocessing techniques, including smoothing, taking derivative and standard
      normal variate (SNV) transformation were used to improve the classification
      performance. The results indicate that smoothing, taking second-order derivatives
      and SNV can improve the class models by enhancing signal-to-noise ratio, reducing
      baseline and background shifts. The most accurate and stable models were obtained
      with SNV spectra for both SIMCA (sensitivity 0.909 and specificity 0.938) and
      PLSCM (sensitivity 0.909 and specificity 0.925). Moreover, both SIMCA and PLSCM
      could detect LRP samples mixed with 5% (w/w) or more other cheaper starches,
      including cassava, sweet potato, potato and maize starches. Although it is
      difficult to perform an exhaustive collection of all pure LRP samples and
      possible adulterations, NIR spectrometry combined with class modeling techniques
      provides a reliable and effective method to detect most of the current LRP
      adulterations in Chinese market. 

PMID- 23870979
TI  - Effects of drying methods on qualitative and quantitative properties of essential
      oil of two basil landraces.
AB  - Sweet basil, a plant that is extensively cultivated in some countries, is used to
      enhance the flavour of salads, sauces, pasta and confectioneries as both a fresh
      and dried herb. To determine the effect of drying methods on qualitative and
      quantitative characteristics of the plant and essential oil of basil, two
      landraces, Purple and Green, were dried in sunlight, shade, mechanical ovens at
      40  degrees C and 60  degrees C, a microwave oven at 500 W and by freeze-drying.
      For comparison, the essential oils of all samples were extracted by
      hydrodistillation and analyzed using GC and GC-MS. The highest essential oil
      yields (v/w on dry weight basis) were obtained from shade-dried tissue in both
      landraces followed by the freeze-dried sample of the purple landrace and the
      fresh sample of green landrace. Increasing the drying temperature significantly
      decreased the essential oil content of all samples. Significant changes in the
      chemical profile of the essential oils from each of the landrace were associated
      with the drying method, including the loss of most monoterpene hydrocarbons, as
      compared with fresh samples. No significant differences occurred among several
      constituents in the extracted essential oils, including methyl chavicol
      (estragole), the major compound in the oil of both landraces, whether the plants
      were dried in the shade or sun, oven at 40  degrees C or freeze-dried, as
      compared with a fresh sample. The percentage methyl chavicol in the oil, however,
      decreased significantly when the plant material was dried in the oven at 60 
      degrees C or microwaved. In addition, linalool, the second major compound in the
      purple landrace, and geranial and neral, major compounds in the green landrace,
      decreased significantly when the plant tissue was dried in the oven at 60 
      degrees C or microwaved.

PMID- 23870980
TI  - A novel method to differentiate bovine and porcine gelatins in food products:
      nanoUPLC-ESI-Q-TOF-MS(E) based data independent acquisition technique to detect
      marker peptides in gelatin.
AB  - We presented a novel nanoUPLC-MS(E) workflow method that has potential to
      identify origin of gelatin in some dairy products; yoghurt, cheese and ice cream.
      In this study, the method was performed in two steps. In the first step, gelatin
      was extracted from these products before the MS-sample preparation. In the second
      step, tryptic gelatin peptides were separated and analyzed with ultra-performance
      liquid chromatography and electrospray ionization quadrupole time-of-flight mass
      spectrometry (nanoUPLC-ESI-q-TOF-MS(E)). The novelty of this setup was that it
      functioned in a data independent acquisition mode and that alternate low and
      elevated collision energy was applied to acquire precursor and product ion
      information. This enabled accurate mass acquisition on the peptide level to
      identify the gelatin peptides. The marker peptides specific for porcine and
      bovine could be successfully detected in the gelatin added to the dairy products
      analyzed, revealing that the detection of marker peptides in the digested gelatin
      samples using nanoUPLC-ESI-q-TOF-MS(E) could be an effective method to
      differentiate porcine and bovine gelatin in the dairy products. 

PMID- 23870981
TI  - Determination of polycyclic aromatic hydrocarbons in smoked fish samples by a new
      microextraction technique and method optimisation using response surface
      methodology.
AB  - Microwave-assisted extraction coupled with dispersive liquid-liquid
      microextraction as a recently introduced method was applied to determine
      polycyclic aromatic hydrocarbons in Iranian smoked fish. The results showed that
      the interaction of hydrolysing solution volume with ethanol ratio, volumes of
      extracting and disperser solvent is significant in the obtained model. Optimized
      conditions were: a hydrolysing solution volume 10 ml with 50% ethanol, a pH of 5,
      and extracting and disperser solvent volumes of 150 and 500 MUl respectively. The
      level of 16 polycyclic aromatic hydrocarbons (PAHs) was determined in 80 smoked
      fish consisting of four species. The contamination of benzo[a]pyrene in all
      samples except three was below the European Commission's maximum level of 2 MUg
      kg(-1) for smoked fish, while the ?4 PAHs (benzo[a]pyrene, chrysene,
      benzo[a]anthracene and benzo[b]fluoranthene) were between 3 and 12 MUg kg(-1) wet
      weight in all samples. Of the species examined, Hypophthalmichthys molitrix had
      the highest PAHs (?16).

PMID- 23870982
TI  - Changes in lipids and fishy odour development in skin from Nile tilapia
      (Oreochromis niloticus) stored in ice.
AB  - Changes in lipids, lipoxygenase activity and fishy odour development in the skin
      of Nile tilapia (Oreochromis niloticus) during iced storage of 18 days were
      monitored. Triacylglycerol content of skin decreased with coincidental increases
      in free fatty acid, monoacylglycerol, diacylglycerol and phospholipid contents
      during storage (p<0.05). During iced storage, peroxide value increased at day 9
      and subsequently decreased up to 18 days (p<0.05). Thiobarbituric acid reactive
      substances values and lipoxygenase activity increased throughout 18 days of iced
      storage (p<0.05). With increasing storage time, a progressive formation of
      hydroperoxide was found as evidenced by the increase in amplitude of peak at 3600
      3200 cm(-1) in Fourier transform infrared spectra. Those changes indicated that
      lipid oxidation took place during iced storage. The increase in fishy odour of
      skin was observed as the storage time increased. The development of fishy odour
      in Nile tilapia skin during iced storage was mostly governed by lipid oxidation
      via autoxidation or induced by lipoxygenase. Thus, the extended storage time of
      whole fish resulted in the pronounced changes in lipids and the increased fishy
      odour in the skin.

PMID- 23870984
TI  - A rapid and accurate method for determining protein content in dairy products
      based on asynchronous-injection alternating merging zone flow-injection
      spectrophotometry.
AB  - An accurate and rapid method and a system to determine protein content using
      asynchronous-injection alternating merging zone flow-injection spectrophotometry
      based on reaction between coomassie brilliant blue G250 (CBBG) and protein was
      established. Main merit of our approach is that it can avoid interferences of
      other nitric-compounds in samples, such as melamine and urea. Optimized
      conditions are as follows: Concentrations of CBBG, polyvinyl alcohol (PVA), NaCl
      and HCl are 150 mg/l, 30 mg/l, 0.1 mol/l and 1.0% (v/v), respectively; volumes of
      the sample and reagent are 150 MUl and 30 MUl, respectively; length of a reaction
      coil is 200 cm; total flow rate is 2.65 ml/min. The linear range of the method is
      0.5-15 mg/l (BSA), its detection limit is 0.05 mg/l, relative standard deviation
      is less than 1.87% (n=11), and analytical speed is 60 samples per hour.

PMID- 23870983
TI  - Light exposure inhibiting tissue browning and improving antioxidant capacity of
      fresh-cut celery (Apium graveolens var. dulce).
AB  - Fresh-cut celery is perishable and susceptible to tissue browning during storage.
      In this study, the effect of continuous light exposure (2000 lux) on browning
      related enzyme activity of fresh-cut celery was investigated during 8d storage at
      7  degrees C using darkness (0.2 lux) as control. Light exposure significantly
      suppressed polyphenol oxidase (PPO) and peroxidase (POD) activities, and
      subsequently decreased soluble quinone accumulation and browning index (BI)
      evolution during storage. In addition, phenylalanine ammonia lyase (PAL)
      activity, total phenol (TP) content, and antioxidant capacity (AC) values were
      all higher when the fresh-cut celery samples were exposed to light than in
      darkness during storage. A significant positive correlation between TP and AC was
      observed at both light (R=0.884, P<0.01) and dark (R=0.705, P<0.01) conditions.

PMID- 23870985
TI  - Characterisation and optimisation of physical and oxidative stability of
      structured lipid-based infant formula emulsion: effects of emulsifiers and
      biopolymer thickeners.
AB  - Response surface methodology (RSM) was applied to investigate the effects of
      lecithin (0-0.4 g/100 ml), monoacylglycerol (0-0.4 g/100 ml), locust bean gum
      (LBG; 0-0.1 g/100 ml), and carrageenan (0-0.02 g/100 ml) on the physical and
      oxidative properties of structured lipid-based infant formula emulsion containing
      dairy proteins, lactose, vitamins, minerals and other micronutrients. Particle
      size, optical stability, viscosity, relative content of docosahexaenoic acid,
      stearidonic acid and total oxidation value were assessed during 28-day storage.
      ANOVA results showed that the experimental data were satisfactorily fitted to
      second-order polynomial models by multiple linear regression. The contour plots
      illustrated that lecithin and monoacylglycerol played a dominant role in
      controlling the emulsion stability compared to LBG and carrageenan. Lecithin
      content significantly affected all the responses measured, particularly lipid
      oxidation. Increasing monoacylglycerol concentration led to an increase in
      particle size and emulsion viscosity. The optimal condition to achieve the
      highest stability was predicted to be 0.2, 0.4, 0.045, and 0.015 g/100 ml
      lecithin, monoacylglycerol, LBG and carrageenan, respectively. The verification
      data further demonstrated the suitability of the models explored by RSM. Overall,
      the findings obtained in this study have important implications for the
      successful incorporation of structured lipid into infant formula emulsion for
      better infant nutrition and health.

PMID- 23870986
TI  - The influence of dehydrated potatoes processing on the glycoalkaloids content in
      coloured-fleshed potato.
AB  - The aim of this study was to determine the effect of different temperatures of
      blanching and pre-drying used in the laboratory production of dried potato dice
      on the content of glycoalkaloids in red and blue fleshed potato varieties.
      Studied potatoes of coloured fleshed varieties were characterised by a low
      glycoalkaloids content at 5.47 mg 100 g(-1). The production of dehydrated potato
      dice influenced on the decrease in glycoalkaloids content in potato products. The
      majority of these compounds were removed during the peeling (70%) and blanching
      process (29%). Potato dice blanched at the highest temperature (85  degrees C)
      and pre-dried at 120  degrees C was characterised by the lowest quantity of
      glycoalkaloids content, whereas the highest content of these compounds was found
      in dice blanched potato at the lowest temperature (65  degrees C) and pre-dried
      at 120  degrees C. The blanching process much influenced on the decrease in
      glycoalkaloids content than pre-drying process.

PMID- 23870988
TI  - Characterisation of proanthocyanidins from black soybeans: isolation and
      characterisation of proanthocyanidin oligomers from black soybean seed coats.
AB  - Proanthocyanidin oligomers (dimers to tetramers) were isolated from black soybean
      seed coats, using Sephadex LH-20 column chromatography and reversed-phase
      preparative HPLC. The isolated oligomers consisted of only (-)-epicatechin units,
      which were linked through either 4beta->8 or 4beta->6 (B-type) bonds. Procyanidin
      B2, procyanidin C1, and cinnamtannin A2 were identified as the main compounds of
      the proanthocyanidin dimers, trimers, and tetramers, respectively. 

PMID- 23870987
TI  - Metabolic profile and biological activities of Lavandula pedunculata subsp.
      lusitanica (Chaytor) Franco: studies on the essential oil and polar extracts.
AB  - We investigated the metabolic profile and biological activities of the essential
      oil and polar extracts of Lavandula pedunculata subsp. lusitanica (Chaytor)
      Franco collected in south Portugal. Gas chromatography-mass spectrometry (GC-MS)
      analysis revealed that oxygen-containing monoterpenes was the principal group of
      compounds identified in the essential oil. Camphor (40.6%) and fenchone (38.0%)
      were found as the major constituents. High-performance liquid chromatography with
      diode array detection (HPLC-DAD) analysis allowed the identification of
      hydroxycinnamic acids (3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic
      and rosmarinic acids) and flavones (luteolin and apigenin) in the polar extracts,
      with rosmarinic acid being the main compound in most of them. The bioactive
      compounds from L. pedunculata polar extracts were the most efficient free-radical
      scavengers, Fe(2+) chelators and inhibitors of malondialdehyde production, while
      the essential oil was the most active against acetylcholinesterase. Our results
      reveal that the subspecies of L. pedunculata studied is a potential source of
      active metabolites with a positive effect on human health. 

PMID- 23870989
TI  - Increased flavour diversity of Chardonnay wines by spontaneous fermentation and
      co-fermentation with Hanseniaspora vineae.
AB  - Discovery, characterisation and use of novel yeast strains for winemaking is
      increasingly regarded as a way for improving quality and to provide variation,
      including subtle characteristic differences in fine wines. The objective of this
      work was to evaluate the use of a native apiculate strain, selected from grapes,
      Hanseniaspora vineae (H. vineae) 02/5A. Fermentations were done in triplicate,
      working with 225 L oak barrels, using a Chardonnay grape must. Three yeast
      fermentation strategies were compared: conventional inoculation with a commercial
      Saccharomyces cerevisiae strain, ALG 804, sequential inoculation with H. vineae
      and then strain ALG 804 and spontaneous fermentation. Yeast strain identification
      was performed during fermentation, in which the apiculate strain was found to be
      active, until 9% of alcohol in volume, for the co-fermentation and the
      spontaneous fermentation was completed by three native S. cerevisiae strains.
      Basic winemaking parameters and some key chemical analysis, such as concentration
      of glycerol, biogenic amines, organic acids, and aroma compounds were analysed.
      Sensory analysis was done using a trained panel and further evaluated with
      professional winemakers. Sequential inoculation with H. vineae followed by S.
      cerevisiae resulted in relatively dry wines, with increased aroma and flavour
      diversity compared with wines resulting from inoculation with S. cerevisiae
      alone. Wines produced from sequential inoculations were considered, by a
      winemaker's panel, to have an increased palate length and body. Characteristics
      of wines derived from sequential inoculation could be explained due to
      significant increases in glycerol and acetyl and ethyl ester flavour compounds
      and relative decreases in alcohols and fatty acids. Aroma sensory analysis of
      wine character and flavour, attributed to winemaking using H. vineae, indicated a
      significant increase in fruit intensity described as banana, pear, apple, citric
      fruits and guava. GC analysis of the relative accumulation of 23 compounds to
      significantly different concentrations for the three fermentation strategies is
      discussed in relation to aroma compound composition.

PMID- 23870990
TI  - Application of novel loop-mediated isothermal amplification (LAMP) for rapid
      authentication of the herbal tea ingredient Hedyotis diffusa Willd.
AB  - Hedyotis diffusa Willd. (Baihuasheshecao) is an ingredient of herbal teas
      commonly consumed in the Orient and tropical Asia for cancer treatment and health
      maintenance. In the market, this ingredient is frequently adulterated by the
      related species Hedyotis corymbosa (L.) Lam. The objective of this study is to
      develop a novel loop-mediated isothermal amplification (LAMP) technique to
      differentiate H. diffusa from its adulterant H. corymbosa. A set of four internal
      control primers (F3, FIP, BIP and B3) were designed based on six loci in the
      internal transcribed spacer (ITS) for LAMP of both H. diffusa and H. corymbosa.
      Two specific primers (S_F3 and S_FIP) were designed for specific LAMP detection
      of H. diffusa only. Our data showed that LAMP was successful for both H. diffusa
      and H. corymbosa in internal control. In contrast, only H. diffusa was detected
      in specific LAMP using the specific primers S_F3 and S_FIP. This study showed
      that LAMP was useful to differentiate H. diffusa from its adulterant H.
      corymbosa. This study is significant for the verification of the authenticity for
      better quality control of this common herbal tea ingredient. The strategy of
      including an internal control assures the quality of the concerned DNA region for
      LAMP. 

PMID- 23870991
TI  - Salmonella detection using 16S ribosomal DNA/RNA probe-gold nanoparticles and
      lateral flow immunoassay.
AB  - An ultrasensitive, simple, and fast lateral flow immunoassay for Salmonella
      detection using gold nanoparticles conjugated with a DNA probe, which is
      complementary to the 16S ribosomal RNA and DNA of Salmonella, has been developed.
      The detection limit is 5 fmol for the synthetic single-stranded DNA. For the
      Salmonella cultured samples, the nucleic acids from 10(7) bacteria were rapidly
      detected in 30 min. After silver enhancement, the detection limit was as low as
      10(4) cells which is lower than 10(5) bacteria cells, the human infective dose of
      food-borne Salmonella. Furthermore, the probes used in this study are specific to
      Salmonella compared to several other Enterobacteriaceae. This approach would be a
      useful tool for microbial detection regarding food safety or clinical diagnosis.
      It is also suitable for large-scale screening in developing countries because it
      is low-cost, sensitive, specific and convenient.

PMID- 23870992
TI  - Beer classification by means of a potentiometric electronic tongue.
AB  - In this work, an electronic tongue (ET) system based on an array of
      potentiometric ion-selective electrodes (ISEs) for the discrimination of
      different commercial beer types is presented. The array was formed by 21 ISEs
      combining both cationic and anionic sensors with others with generic response.
      For this purpose beer samples were analyzed with the ET without any pretreatment
      rather than the smooth agitation of the samples with a magnetic stirrer in order
      to reduce the foaming of samples, which could interfere into the measurements.
      Then, the obtained responses were evaluated using two different pattern
      recognition methods, principal component analysis (PCA), which allowed
      identifying some initial patterns, and linear discriminant analysis (LDA) in
      order to achieve the correct recognition of sample varieties (81.9% accuracy). In
      the case of LDA, a stepwise inclusion method for variable selection based on
      Mahalanobis distance criteria was used to select the most discriminating
      variables. In this respect, the results showed that the use of supervised pattern
      recognition methods such as LDA is a good alternative for the resolution of
      complex identification situations. In addition, in order to show an ET
      quantitative application, beer alcohol content was predicted from the array data
      employing an artificial neural network model (root mean square error for testing
      subset was 0.131 abv). 

PMID- 23870993
TI  - Characterisation of volatile profile in soymilk treated by ultra high pressure
      homogenisation.
AB  - The effect of ultra high pressure homogenisation (UHPH) on the volatile profile
      of soymilk was studied and compared with conventional treatments. Soymilk was
      treated at 200 MPa combined with two inlet temperatures (55 or 75  degrees C) and
      treated at 300 MPa at 80  degrees C inlet temperature. UHPH-treated soymilks were
      compared with base product (untreated sample), pasteurised soymilk (90  degrees
      C, 30s) and ultra high temperature (UHT; 142  degrees C, 6s) treated samples.
      Volatile compounds were extracted by solid-phase microextraction and were
      identified by gas chromatography coupled with mass spectrometry. Pasteurisation
      and UHPH treatments at 200 MPa produced few changes in the volatile composition,
      reaching similar values to untreated soymilk. UHT treatment produced the most
      important effects on volatile profile compared to UHPH at 300MPa and 80  degrees
      C. Hexanal was the most abundant compound detected in all treatments. The effect
      of UHPH technology on volatile profile induced modifications depending on the
      combinations of processing parameters.

PMID- 23870994
TI  - Nutritional and technological quality of bread enriched with an intermediated
      pearled wheat fraction.
AB  - A strategy to maximise the health benefits of wheat-based products enriched with
      refined flour and selected fractions of kernel, obtained by sequential pearling,
      has been tested. Five mixtures of refined commercial flour with an increasing
      replacement of a pearled wheat fraction were used to prepare bread and were
      compared with a control for the dough rheological properties (Mixolab(r)
      parameters), the bioactive compound content, deoxynivalenol (DON) contamination
      and the physical properties (volume, crust colour, instrumental crunchiness and
      crumb texture profile analysis parameters). The antioxidant and dietary fibre
      contents increased linearly as the flour was enriched with the pearled fraction.
      The dietary fibre, beta-glucan, total phenolic, alkylresorcinol content and the
      antioxidant activity increased significantly at a replacement level of 10%, while
      the technological properties were not significantly different from those of the
      control. It has been shown that refined flour could be enriched through the
      addition of a selected wheat pearled fraction and the bioactive compound content
      of composite bread could be improved, while few rheological and technological
      differences could be obtained and the risk for DON contamination could be
      limited. 

PMID- 23870995
TI  - Effect of high pressure treatments on the physicochemical properties of a sulphur
      dioxide-free red wine.
AB  - The application of high hydrostatic pressure (HHP) in winemaking for substitution
      of the use of sulphur dioxide is still at a very early stage of development,
      since knowledge about the effect on physicochemical and sensorial characteristics
      of the wine during storage is very scarce. In this work, the evolution of colour,
      antioxidant activity and total phenolic compounds of SO2-free red wines treated
      by HHP and aged in bottles was followed for 12 months. The pressurised wines were
      compared with wine samples prepared with addition of 40 ppm of SO2 and without
      any of these two treatments. After 12 months, the pressurised wines presented
      higher values of CIELab parameters (a(*), b(*), and L(*)) and a lower monomeric
      anthocyanin content (45-61%) when compared to the unpressurised ones. The
      pressurised wines showed also a better global sensorial assessment, with the
      pressure treatments imparting aged-like characteristics to the wines. The wine
      deposits of pressurised wines had higher total phenolic content, namely
      proanthocyanidins (3- to 10-fold). The results demonstrate that HHP can influence
      long term red wine physicochemical and sensorial characteristics, hypothesised to
      be due to an increase of condensation reactions of phenolic compounds, forming
      compounds with higher degree of polymerisation that became insoluble in wine
      along storage.

PMID- 23870996
TI  - The hydroxycinnamic acid content of barley and brewers' spent grain (BSG) and the
      potential to incorporate phenolic extracts of BSG as antioxidants into fruit
      beverages.
AB  - The hydroxycinnamic acid (HA) content of starting barley for brewers' spent
      grains (BSG), whole BSG and phenolic extracts from BSG was measured using high
      performance liquid chromatography (HPLC) and correlated with antioxidant
      potential. The effect of BSG phenolic extracts on antioxidant activity of fruit
      beverages was also assessed (using the total phenolic content (TPC), 2,2-diphenyl
      1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays). The
      concentration of HA present in barley extract and BSG was in the order of ferulic
      acid (FA), p-coumaric acid (p-CA) derivatives, FA derivatives, p-CA, caffeic acid
      (CA) and CA derivatives. Results suggested that brewing and roasting decreased
      the HA content. Antioxidant activity was significantly (P<0.05) correlated with
      caffeic acid (R(2)=0.8309) and total HA (R(2)=0.3942) concentrations. Addition of
      extracts to fruit beverages resulted in a significant (P<0.05) increase in
      antioxidant activity of cranberry juice, measured by the FRAP assay. In vitro
      digestion significantly (P<0.05) reduced TPC, DPPH and FRAP activity of the fruit
      beverages. 

PMID- 23870997
TI  - Chemical composition of virgin olive oils according to the ripening in olives.
AB  - The aim of this study was the classification of olive oil according to the stage
      of ripeness of the olives used for its manufacture. A discriminant analysis was
      applied taking as dependent variables the fatty acids, triglycerides and sterols
      profile. The evolution of parameters of quality of the oils during ripening of
      the fruit has also been studied in three successive crops. The results of the
      classification shows that 88.5% of selected original grouped cases are correctly
      classified (85.7% green, 80% spotted and 78.9% ripe) and furthermore the
      validation classified the 69.6% of the unselected original cases. The most
      discriminating variables have been: avenasterol, linolenic acid, beta-sitosterol
      and gadoleico. Fig. 1 shows graphically the values of the canonical discriminant
      functions and the centroids of the intervals of three or the maturity index. 

PMID- 23870998
TI  - Intrinsic isotopic 13C labelling of polyphenols.
AB  - The intrinsic isotopic labelling of plants with (13)CO2 is an effective method to
      generate highly labelled compounds using photosynthesis and avoiding labour
      intensive complex organic syntheses. In this study, the intrinsic isotopic
      labelling of polyphenols in parsley, spinach and peppermint is shown for the
      first time. The plants were grown in an atmosphere where (12)CO2 was replaced by
      (13)CO2, in order to generate highly labelled compounds. The total content of
      (13)C as well as the individual polyphenols were analysed by Isotopic Ratio-MS
      and HPLC-Iontrap-MS(n). After 34 days of plant growth under (13)CO2, degree of
      labelling was found to be higher than 90 atom% (13)C for most polyphenols,
      predominantly consisting of highly and fully labelled isotopomers; the total
      plant material contained more than 88 atom% (13)C. Such highly labelled compounds
      can be used in future studies to dissect both metabolism and bioavailability of
      polyphenols in humans.

PMID- 23870999
TI  - Antitumor efficacy of piperine in the treatment of human HER2-overexpressing
      breast cancer cells.
AB  - Piperine is a bioactive component of black pepper, Piper nigrum Linn, commonly
      used for daily consumption and in traditional medicine. Here, the molecular
      mechanisms by which piperine exerts antitumor effects in HER2-overexpressing
      breast cancer cells was investigated. The results showed that piperine strongly
      inhibited proliferation and induced apoptosis through caspase-3 activation and
      PARP cleavage. Furthermore, piperine inhibited HER2 gene expression at the
      transcriptional level. Blockade of ERK1/2 signaling by piperine significantly
      reduced SREBP-1 and FAS expression. Piperine strongly suppressed EGF-induced MMP
      9 expression through inhibition of AP-1 and NF-kappaB activation by interfering
      with ERK1/2, p38 MAPK, and Akt signaling pathways resulting in a reduction in
      migration. Finally, piperine pretreatment enhanced sensitization to paclitaxel
      killing in HER2-overexpressing breast cancer cells. Our findings suggest that
      piperine may be a potential agent for the prevention and treatment of human
      breast cancer with HER2 overexpression. 

PMID- 23871000
TI  - Interactions of starch with a cyanidin-catechin pigment (vignacyanidin) isolated
      from Vigna angularis bean.
AB  - A cyanidin-catechin pigment isolated from adzuki bean (vignacyanidin) interacted
      with starch. The pigment had absorption maxima at 530 and 540 nm at pH 2.0 and
      6.8, respectively, and starch (10 and 100 mg ml(-1)) increased the absorbance,
      shifting the absorption maxima to longer wavelengths. Nitrite oxidised
      vignacyanidin at pH 2.0, and the oxidation resulted in the production of nitric
      oxide (NO). Rates of the oxidation and the NO production were enhanced by starch.
      Vignacyanidin inhibited alpha-amylase-catalysed digestion of starch at pH 6.8,
      and amylose digestion was more effectively inhibited than amylopectin digestion.
      The above results suggest (i) that binding of the pigment to starch increased the
      accessibility of nitrous acid to the pigment, and (ii) that the binding reduced
      the digestibility of starch by alpha-amylase. Possible functions of the pigment
      in the stomach and the intestine are postulated, taking the above results into
      account.

PMID- 23871001
TI  - The effect of domestic processing on the content and bioaccessibility of
      carotenoids from chili peppers (Capsicum species).
AB  - The content and bioaccessibility of carotenoids from different chili peppers were
      analysed and the effects of typical domestic processing were investigated.
      Peppers were analysed before and after cooking by conventional boiling (10 min in
      100  degrees C water) and also following a freezing period of four months in a
      domestic freezer (-20  degrees C). The content and bioaccessibility of the eight
      carotenoids quantified varied, depending on cultivar, species, colour and
      processing. Provitamin A carotenoids (beta-carotene and beta-cryptoxanthin) and
      capsanthin were present at highest concentrations in the samples before and after
      processing. In general, yellow and orange peppers were the best sources of
      lutein, zeaxanthin and neoxanthin. Xanthophyll carotenoids were more efficiently
      transferred to the micelles and, therefore, were also more bioavailable.
      Processing decreased the carotenoid content in certain samples; however, the
      micellar content was generally not lower for processed peppers; therefore the
      bioaccessibility of carotenoids from processed peppers is enhanced relative to
      unprocessed peppers.

PMID- 23871002
TI  - GFAAS determination of mercury in muscle samples of fish from Amazon, Brazil.
AB  - In the present study, a simple, rapid and sensitive method was developed for the
      determination of mercury concentrations in the muscle tissue of fish from the
      Brazilian Amazon using graphite furnace atomic absorption spectrometry (GFAAS)
      following acid mineralization of the samples in an ultrasonic cold water bath.
      Using copper nitrate as a chemical modifier in solution and sodium tungstate as
      permanent modifier, we were able to attain thermal stabilization of the mercury
      up to the atomisation temperature of 1600  degrees C in the GFAAS assay. The
      calculated limits of detection (LOD) and quantification (LOQ) were 0.014 and
      0.047 mg kg(-1), respectively.

PMID- 23871003
TI  - Evaluation of real-time PCR detection methods for detecting rice products
      contaminated by rice genetically modified with a CpTI-KDEL-T-nos transgenic
      construct.
AB  - Genetically modified (GM) rice (Oryza sativa) lines, such as insecticidal Kefeng
      and Kemingdao, have been developed and found unauthorised in processed rice
      products in many countries. Therefore, qualitative detection methods for the GM
      rice are required for the GM food regulation. A transgenic construct for
      expressing cowpea (Vigna unguiculata) trypsin inhibitor (CpTI) was detected in
      some imported processed rice products contaminated with Kemingdao. The 3'
      terminal sequence of the identified transgenic construct for expression of CpTI
      included an endoplasmic reticulum retention signal coding sequence (KDEL) and
      nopaline synthase terminator (T-nos). The sequence was identical to that in a
      report on Kefeng. A novel construct-specific real-time polymerase chain reaction
      (PCR) detection method for detecting the junction region sequence between the
      CpTI-KDEL and T-nos was developed. The imported processed rice products were
      evaluated for the contamination of the GM rice using the developed construct
      specific real-time PCR methods, and detection frequency was compared with five
      event-specific detection methods. The construct-specific detection methods
      detected the GM rice at higher frequency than the event-specific detection
      methods. Therefore, we propose that the construct-specific detection method is a
      beneficial tool for screening the contamination of GM rice lines, such as Kefeng,
      in processed rice products for the GM food regulation. 

PMID- 23871004
TI  - Buckwheat trypsin inhibitor enters Hep G2 cells by clathrin-dependent
      endocytosis.
AB  - Recombinant buckwheat trypsin inhibitor (rBTI) was studied to evaluate if it
      could enter cancer cells and to determine the mechanism. Fluorescein
      isothiocyanate-labelled buckwheat trypsin inhibitor (FITC-BTI) entered Hep G2
      cells in a concentration-dependent manner. FITC-BTI colocalised with labelled
      transferrin (Tf) in the punctate structure, implying that rBTI enters Hep G2
      cells by clathrin-dependent endocytosis. Incubation of Hep G2 cells with
      different chemical inhibitors abolished diffuse, but not punctate fluorescence,
      thus indicating that membrane potential plays a critical role in this process.
      Impairment of clathrin-mediated endocytosis by RNAi with clathrin heavy chain
      greatly reduced or completely abolished both diffuse and punctate fluorescence,
      further supporting a theory of a single route of endocytosis. Consistent with our
      working hypothesis, Hep G2 cells which were arrested in the M phase did not show
      any vesicular or diffuse FITC-BTI. We conclude from these results that both
      endocytosis and membrane potential are required for rBTI entry into Hep G2 cells.

PMID- 23871005
TI  - Determination of lead in rice grains by solid sampling HR-CS GFAAS.
AB  - A study was performed for the determination of lead in rice grains directly by
      solid sampling high resolution continuum source graphite furnace atomic
      absorption spectrometry (HR-CS GFAAS) without digesting sample. The effects of
      sample amount, pyrolysis/atomization temperatures on the determination of lead in
      rice were investigated and optimized using a certificated rice flour. The lead
      concentrations were determined applying 800  degrees C of pyrolysis and 1800 
      degrees C of atomization temperatures without modifier. LOD (N=10, 3sigma) and
      characteristic mass were 2.3 MUg kg(-1) and 8.1 pg, respectively. The certified
      lead value of a rice flour CRM was found in its uncertainity limits. The lead
      contents of various rice samples obtained from markets in Turkey were between
      0.009 and 0.162 mg kg(-1) which are in acceptable range. The average lead
      concentrations in various rice grains taken from the same package were
      significantly different from each other.

PMID- 23871006
TI  - Evaluation of different validation strategies and long term effects in NIR
      calibration models.
AB  - Stable and reliable NIR calibration models for the barley malt quality assessment
      were developed and exhaustively evaluated. The measured parameters are: fine
      extract, fermentability, pH, soluble nitrogen, viscosity, friability and free
      amino nitrogen. The reliability of the developed calibration models was evaluated
      comparing the classic leave-one-out internal validation with a more challenging
      one exploiting re-sampling scheme. The long-term effects, intended as possible
      alterations of the NIR method predictive power, due to the variation between
      samples collected in different years, were evaluated through an external
      validation which demonstrated the stability of the developed calibration models.
      Finally, the accuracy and the precision of the developed calibration models were
      evaluated in comparison with the reference methods. This exhaustive evaluation
      offers a realistic idea of the developed NIR methods predictive power for future
      unknown samples and their application in the beer industry. 

PMID- 23871007
TI  - Total phenolics, antioxidant activity, and functional properties of 'Tommy
      Atkins' mango peel and kernel as affected by drying methods.
AB  - Mango processing produces significant amount of waste (peels and kernels) that
      can be utilized for the production of value-added ingredients for various food
      applications. Mango peel and kernel were dried using different techniques, such
      as freeze drying, hot air, vacuum and infrared. Freeze dried mango waste had
      higher antioxidant properties than those from other techniques. The ORAC values
      of peel and kernel varied from 418-776 and 1547-1819 MUmol TE/g db. The
      solubility of freeze dried peel and kernel powder was the highest. The water and
      oil absorption index of mango waste powders ranged between 1.83-6.05 and 1.66
      3.10, respectively. Freeze dried powders had the lowest bulk density values among
      different techniques tried. The cabinet dried waste powders can be potentially
      used in food products to enhance their nutritional and antioxidant properties.

PMID- 23871008
TI  - Hydroperoxide formation in different lean meats.
AB  - Peroxide is one of the compounds that are indicated to be toxic in the human
      digestion system. Lean fresh meat samples were collected from beef, lamb, pork
      and chicken to investigate their hydroperoxide formation potential. Total
      peroxides of fresh comminuted raw meat were determined by analysing protein-bound
      peroxides and hydroperoxide compounds in water-methanol and chloroform extracted
      phases. The amount of total peroxides was ranked as: beef>pork>lamb>chicken.
      Hydroperoxide formation was examined at different pH values and at different
      incubation times, using beef and chicken samples. All peroxides were transient,
      with a maximum value after 2-4 h of incubation at 37  degrees C. When pH fell
      from 7 to 1.5, the different peroxides fell by 10-20%. Non-polar peroxide
      formation could largely (70%) be described by variation in fatty acid composition
      and hemin content of the meat, while protein-bound peroxide variation was less
      explained by these variables. Liposome addition increased (40%) the amount of
      protein-bound peroxides.

PMID- 23871009
TI  - Effects of tea polyphenols on the post-mortem integrity of large yellow croaker
      (Pseudosciaena crocea) fillet proteins.
AB  - Tea polyphenols (TP) are known to be important for the post-mortem deterioration
      of fish muscle and can enhance food quality. To shed light on the influence of TP
      on the status of large yellow croaker muscle proteins, control and treated
      fillets (0.1% TP, 0.2% TP and 0.3% TP, w/v) were analysed periodically for
      myofibrillar protein functional properties (Ca(2+)-ATPase activity, surface
      hydrophobicity, total sulfhydryl content, emulsion stability index and
      rheological behaviour). Degradation of the myofibrillar protein myosin could be
      clearly observed; several proteins were also observed to vary in abundance
      following post-mortem storage for 25 days. The present study offers new evidence
      that TP have an effective impact on muscle protein integrity post-mortem.

PMID- 23871010
TI  - Evaluation of an analytical methodology using QuEChERS and GC-SQ/MS for the
      investigation of the level of pesticide residues in Brazilian melons.
AB  - A multiresidue method based on the sample preparation by modified QuEChERS and
      detection by gas chromatography coupled to single quadruple mass spectrometers
      (GC-SQ/MS) was used for the analysis of 35 multiclass pesticides in melons
      (Cucumis melo inodorus) produced in Ceara-Brazil. The rates of recovery for
      pesticides studied were satisfactory (except for the etridiazole), ranging from
      85% to 117% with a relative standard deviation (RSD) of less than 15%, at
      concentrations between 0.05 and 0.20 mg kg(-1). The limit of quantification (LOQ)
      for most compounds was below the MRLs established in Brazil. The combined
      relative uncertainty (Uc) and expanded uncertainty (Ue) was determined using
      repeatability, recovery and calibration curves data for each pesticide. Analysis
      of commercial melons samples revealed the presence of pesticides bifenthrin and
      imazalil at levels below the MRLs established by ANVISA, EU and USEPA.

PMID- 23871011
TI  - LC-MS/MS coupled with QSAR modeling in characterising of angiotensin I-converting
      enzyme inhibitory peptides from soybean proteins.
AB  - The importance of soy products in reducing the risk of cardiovascular disease is
      well documented. Our previous computation study has indicated the presence of
      several potent ACE inhibitory peptides within soybean proteins which needs to be
      identified. The aim of the study was to identify ACE inhibitory peptides from soy
      proteins using LC-MS/MS coupled with quantitative structure-activity relationship
      (QSAR) model. Soybean protein hydrolysate digested by thermolysin showed an IC50
      value of 53.6 MUg/mL, decreased slightly to 51.8 MUg/mL after adding pepsin, and
      increased to 115.6 MUg/mL after adding trypsin. A total of 34 peptides were
      characterised from LC-MS/MS. Five novel tripeptides, IVF, LLF, LNF, LSW and LEF,
      with predicted IC50 values lower than 10 MUM were synthesized and validated. The
      results showed that soybean is an excellent source of ACE inhibitory peptides.

PMID- 23871012
TI  - Flavan-3-ol-cysteine and acetylcysteine conjugates from edible reagents and the
      stems of Cynomorium songaricum as potent antioxidants.
AB  - Flavan-3-ol derivatives, including 3 cysteine conjugates and 3 acetylcysteine
      conjugates, were prepared using Cynomorium songaricum and edible reagents. The
      structures were determined, based on NMR and MS spectra. All compounds had
      stronger radical-scavenging activity than catechin and epicatechin. Moreover, the
      cysteine conjugates were active against alpha-glucosidase, whereas catechin and
      epicatechin were not. Two acetylcysteine flavan-3-ol conjugates, 4beta-(L
      acetylcysteinyl)-epicatechin 3-O-gallate and 4beta-(L-acetylcysteinyl)
      epiafzelechin, are novel compounds with better logP values than their cysteine
      counterparts. These conjugates can be prepared from purified flavan-3-ol polymers
      or directly from herbal material.

PMID- 23871013
TI  - Identification and quantification of free, conjugate and total phenolic compounds
      in leaves of 20 sweetpotato cultivars by HPLC-DAD and HPLC-ESI-MS/MS.
AB  - The study systematically investigated free, conjugate and total phenolics
      (phenolic acids and flavonoids) in leaves of 19 Chinese and one American
      sweetpotato cultivars grown in China. Three extraction/hydrolytic methods (direct
      extraction and acidic and basic hydrolysis) for sample preparation were employed
      to obtain different forms of phenolics. Twenty-nine phenolics were separated and
      identified using HPLC-DAD and HPLC-ESI-MS/MS. Three quercetin glycosides were
      characterised for the first time from this plant. Contents of the principal
      phenolics identified were determined by the HPLC-DAD procedure, which was
      validated in terms of linearity, precision, accuracy and limit of detection and
      quantification. Moreover, to the best of our knowledge, it is the first to reveal
      and demonstrate artifacts of esterification during acidic methanolic and
      ethanolic hydrolysis, and chromatographic behaviours, UV spectra and MS data of
      20 hydroxycinnamic acid methyl and ethyl esters were obtained using acidic
      methanolic and ethanolic hydrolysis. 

PMID- 23871014
TI  - Encapsulation of coenzyme Q10 in a simple emulsion-based nutraceutical
      formulation and application in cheese manufacturing.
AB  - Coenzyme Q10 (CoQ10) was encapsulated successfully in a nutraceutical formulation
      composed of calcium caseinate, flaxseed oil and lecithin. The effect of CoQ10 on
      the physico-chemical stability of emulsions was compared to emulsions without
      CoQ10. According to ATR-FTIR analysis, emulsions were found to be more stable in
      the presence of CoQ10. The emulsion with CoQ10 was used as a functional cream in
      the cheese making process. The retention rate of CoQ10, composition and cheese
      yield were also determined. Quantification of CoQ10 by HPLC showed that the
      retention of this lipophilic agent into cheese matrix was 93% and equivalent to
      the total lipid retention. Protein retention and cheese yield were not affected
      by the addition of the functional cream. For the first time, CoQ10 has been
      encapsulated in a cheese matrix, hence demonstrating that CoQ10 could be used in
      the development of functional cheeses. 

PMID- 23871015
TI  - A survey of biogenic amines in vinegars.
AB  - This paper reports the determination of biogenic amines by high-performance
      liquid chromatography (HPLC) and fluorescence detection after derivatization with
      6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) in balsamic, apple, and
      red, white, and Sherry wine vinegars. A solid-phase extraction (SPE) with mixed
      mode resins method was used before analysis. The method was successfully
      validated obtaining adequate values of selectivity, response linearity,
      precision, accuracy, and low detection and quantification limits. The total
      content of biogenic amines in vinegars ranged from 23.35 to 1445.2 MUg/L, being
      lower than those reported in wines. Putrescine was the amine that showed the
      highest concentrations in most samples. Methylamine and phenylethylamine were not
      determined in any vinegar. Balsamic and "Pedro Ximenez" Sherry vinegars reached
      the highest amounts of biogenic amines, while apple, white and Sherry wine
      vinegars had the lowest concentrations. Principal component analysis using the
      biogenic amines as variables, allowed to separate the different kind of vinegars,
      excepting red vinegars.

PMID- 23871016
TI  - Low-temperature cleanup with solid-phase extraction for the determination of
      polycyclic aromatic hydrocarbons in edible oils by reversed phase liquid
      chromatography with fluorescence detection.
AB  - Low-temperature cleanup, which is a simple and cost-efficient sample preparation
      technique that allows the convenient treatment of multiple samples
      simultaneously, was developed in conjunction with solid-phase extraction (SPE)
      cleanup for the determination of 16 polycyclic aromatic hydrocarbons (PAHs) in
      refined and used edible oil samples by high-performance liquid chromatography
      with fluorescence detection (HPLC-FLD). Samples are extracted with a small amount
      of organic solvent and most of lipids in the extract were removed by low
      temperature cleanup. SPE cartridge was used to further cleanup prior to HPLC-FLD
      analysis. Optimum extraction of low-temperature cleanup was achieved when using
      two extractions with a 4:1 (v/v) mixture of acetonitrile: acetone as the
      extraction solvent, freezing at between -18  degrees C and -25  degrees C for 24
      h and then cleanup with an Alumina-N SPE cartridge. The PAH recoveries were 45.9
      118.5%, with limit of detection (LOD) and limit of quantitation (LOQ) values of
      0.13-3.13 MUg/kg and 0.25-6.25 MUg/kg across the 16 tested PAHs, respectively.
      The validated method was successfully applied for the determination of PAHs in
      reference materials of olive oil and real refined and used edible oil samples.

PMID- 23871017
TI  - Adhesion of enterotoxigenic Escherichia coli strains to neoglycans synthesised
      with prebiotic galactooligosaccharides.
AB  - Enterotoxigenic (ETEC) Escherichia coli (E. coli) causes traveller's diarrhoea
      and high mortality among baby animals. ETEC adhesion is mediated by lectins
      (adhesins) that bind to glycoconjugates on the surface of host cells. Glycans
      that compete for adhesion could be used for disease prevention. Neoglycans of
      porcine albumin (PSA) that were conjugated with prebiotic galactooligosaccharides
      (GOS) were synthesised using the Maillard reaction. PSA glycation was confirmed
      by a reduction in the number of available free amino groups, decreased tryptophan
      intrinsic fluorescence, increased molecular mass and Ricinus communis lectin
      recognition. The adhesion of four ETEC strains (E. coli H10407, CFA(+), K99 and
      K88) to PSA-GOS was examined by an enzyme-linked lectin assay. E. coli K88 bound
      to PSA-GOS with greater affinity (P<0.05) than did E. coli H10407, CFA(+) and
      K99. In addition, PSA-GOS partially inhibited the adherence of the K88 strain to
      intestinal mucins. Pig ETEC strain was unable to ferment galactooligosaccharide
      neoglycans. These results suggest that neoglycans obtained by the Maillard
      reaction may serve in the prophylaxis of ETEC K88 diarrhoea. 

PMID- 23871018
TI  - Simultaneous quantification of caffeine and its three primary metabolites in rat
      plasma by liquid chromatography-tandem mass spectrometry.
AB  - A rapid, sensitive, simple and accurate LC-MS/MS method for the simultaneous
      quantitation of caffeine, and its three primary metabolites, theobromine,
      paraxanthine, and theophylline, in rat plasma was developed and validated.
      Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18
      column using 1 MUg/mL acetaminophen as an internal standard. Each sample was run
      at 0.5 mL/min for a total run time of 7 min/sample. Detection and quantification
      were performed using a mass spectrometer in selected reaction-monitoring mode
      with positive electrospray ionization. The lower limit of quantification was 5
      ng/mL for all analytes with linear ranges up to 5000 ng/mL for caffeine and 1000
      ng/mL for its metabolites. The coefficient of variation for assay precision was
      less than 12.6%, with an accuracy of 93.5-114%. The assay was successfully
      applied to determine plasma concentrations of caffeine, theobromine,
      paraxanthine, and theophylline in rat administered various energy drinks
      containing the same caffeine content. Various energy drinks exhibited
      considerable variability in the pharmacokinetic profiles of caffeine and its
      three primary metabolites, even containing the same caffeine. Different additives
      of energy drinks might contribute to these results.

PMID- 23871019
TI  - Differential changes in grain ultrastructure, amylase, protein and amino acid
      profiles between Tibetan wild and cultivated barleys under drought and salinity
      alone and combined stress.
AB  - Grain phytochemical profiles were compared in Tibetan wild barley XZ5 (drought
      tolerant), XZ16 (salinity/aluminum-tolerant) and cv CM72 (salinity-tolerant) in
      response to drought and salinity alone and combination (D+S) during anthesis.
      Total antioxidant capacity assessed by determining ferric-reducing antioxidant
      potential (FRAP) in grains increased significantly as follows:
      D+S>drought>salinity, and XZ5>XZ16>CM72. A marked increase in the total phenol
      (TP) from individual and combined stresses was observed in XZ5, while a decrease
      occurred in CM72. Moreover, the activity of alpha-/beta-amylase in the grains
      under combined stress was 81.8%/16.9% in XZ5 and 48.6%/18.7% in XZ16 higher than
      that of CM72. Increases in amino acids, protein content and protein fractions of
      albumin, globulin, hordein and glutelin were maximised under D+S, with larger
      values in the Tibetan wild genotypes. Observation with a scanning electron
      microscopy showed a distinct genotypic difference under D+S; for example, XZ5 and
      XZ16 maintained a relatively integral starch granule with a greater protein
      deposit/matrix, while CM72 degraded by pitting. This research expands our
      understanding of barley drought and salt-tolerance mechanisms and provides
      possibility of Tibetan wild barley in developing barley cultivars with both
      tolerance to drought and salinity. 

PMID- 23871020
TI  - Antioxidant enzyme activities are affected by salt content and temperature and
      influence muscle lipid oxidation during dry-salted bacon processing.
AB  - Fresh pork bacon belly was used as material and manufactured into dry-salted
      bacon through salting and drying-ripening. During processing both oxidative
      stability and antioxidant enzyme stability were evaluated by assessing peroxide
      value (PV), thiobarbituric acid reactive substances (TBARS) and activities of
      catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and
      their correlations were also analysed. The results showed that all antioxidant
      enzyme activities decreased (p<0.05) until the end of process; GSH-Px was the
      most unstable one followed by catalase. Antioxidant enzyme activities were
      negatively correlated with TBARS (p<0.05), but the correlations were decreased
      with increasing process temperature. Salt showed inhibitory effect on all
      antioxidant enzyme activities and was concentration dependent. These results
      indicated that when process temperature and salt content were low at the same
      time during dry-salted bacon processing, antioxidant enzymes could effectively
      control lipid oxidation. 

PMID- 23871021
TI  - Thermo-oxidation of cholesterol: effect of the unsaturation degree of the lipid
      matrix.
AB  - The influence of the unsaturation degree of different triacylglycerols
      (tristearin, triolein, trilinolein and trilinolenin) on cholesterol oxidation at
      180  degrees C, was evaluated. Cholesterol degraded faster when heated alone than
      in the presence of triacylglycerols; moreover, the more unsaturated the matrix,
      the slower the degradation of cholesterol. Both cholesterol and triacylglycerols
      degradation fit a first order kinetic model (R(2)>0.9), except for the tristearin
      sample. Cholesterol oxidation products (COPs) and peroxides were formed during
      the heating treatment. The presence of any type of lipid matrix postponed and
      decreased the maximum concentration of both oxidation parameters. Maximum total
      COPs concentrations were achieved at 20 min in neat cholesterol, 120 min in
      tristearin and triolein and 180 min in polyunsaturated matrix samples. 7
      Ketocholesterol was the main COP in most cases during the whole heating
      treatment. Both the presence of triacylglycerols and their unsaturation degree
      inhibited cholesterol thermooxidation at 180  degrees C.

PMID- 23871022
TI  - Peel LTP (Pru p 3)--the major allergen of peach--is methylated. A proteomic
      study.
AB  - Lipid transfer protein (LTP, Pru p 3) is the major allergen of peach (Prunus
      persica), and is in a greater abundance in the peel than in the pulp of the
      fruit. Peel LTP is more allergenic than pulp LTP, but it is not clear whether
      this is due to its specific allergenic properties or to its higher concentration.
      In this study, we have used a new one-step, rapid procedure for the purification
      of LTP from peel and pulp of four peach varieties [Gladys (white flesh),
      California (nectarine yellow flesh), Plusplus (yellow flesh), Red Fair (nectarine
      yellow flesh)] harvested in a field grown in Southern Italy. Purification was
      based on miniature reversed-phase chromatography, a procedure suitable for
      proteomic study. Proteomic analysis of purified LTPs revealed that the amino acid
      sequence of LTP was identical in all peach genotypes but, for the first time,
      peel LTP was found to be methylated. 

PMID- 23871023
TI  - Effect of citric acid deamidation on in vitro digestibility and antioxidant
      properties of wheat gluten.
AB  - The effects of citric acid deamidation on the physiochemical properties of wheat
      gluten were investigated. In vitro digestion was carried out to determine changes
      of molecular weight distribution, amino acids composition and antioxidant
      efficacy of wheat gluten hydrolysates. Results indicated that citric acid
      deamidation significantly increased gluten solubility and surface hydrophobicity,
      at a neutral pH. Deamidation induced molecular weight distribution change of
      gluten with little proteolysis. Results from FTIR indicated that the alpha-helix
      and beta-turn of deamidated gluten increased accompanied by a decrease of the
      beta-sheet structure. After deamidation, in vitro pepsin digestibility of wheat
      gluten decreased, while in vitro pancreatin digestibility increased. The oxygen
      radical absorbance capacity (ORAC) activity of the in vitro digests decreased
      with increase of deamidation time. The high Lys and total essential AAs amounts
      in the final digests suggested that the nutritional values of wheat gluten after
      deamidation might be enhanced. 

PMID- 23871024
TI  - Geographical traceability based on 87Sr/86Sr indicator: a first approach for PDO
      Lambrusco wines from Modena.
AB  - The main goal of this study was to evaluate (87)Sr/(86)Sr ratio in different
      matrices, namely soils, branches, and grape juices, of an oenological food chain
      in order to develop a robust analytical strategy able to link the investigated
      food to its territory of origin. The (87)Sr/(86)Sr has been used as traceability
      marker and several aspects, affected its variability, i.e. geological features of
      the investigated area, the bio-available fraction of elements in the soils and
      the up-take of the plant, have been taken into account. Optimisation of an
      analytical procedure for the separation of Sr from its interferences and
      investigation of the analytical performances in terms of precision of used
      methodology have been carried out as well. This work highlighted a good match
      between the isotopic values monitored in the bio-available fraction of soils and
      their respective grape juices for almost all the investigated areas. The
      correlation with food satisfyingly improves when isotopic relative abundance
      values of branches vine are considered. 

PMID- 23871025
TI  - A modified ninhydrin micro-assay for determination of total cyanogens in plants.
AB  - Indirect quantification of total cyanogenic compounds (cyanogens) in plants was
      studied using a novel ninhydrin-based spectrophotometric micromethod. The
      ninhydrin-cyanide system obeys Beer's law in the range from 20 MUg L(-1) to 800
      MUg L(-1) CN(-) with molar absorptivity epsilon=1.4*10(5) L mol(-1)cm(-1).
      Recovery at 100 MUg L(-1) CN(-) was 100.5+/-0.1% and LOD and LOQ were 8 and 22
      MUg L(-1), respectively. The conditions for ninhydrin reagent preparation were
      discussed. The extraction and separation solutions, extraction and incubation
      time, and solvent volume were also investigated for maximum recovery of total
      cyanogens. 0.1% NaHCO3 was used as an extraction solvent for cyanide formed after
      enzymatic hydrolysis of cyanogens. The procedure was suitable for samples
      containing more than 90 mg CN(-)/100 g sample. When cyanogen concentrations were
      lower, the resulted cyanide was separated by microdiffusion in a Conway cell.
      Water was used as a hydrolysis medium and a donor solvent, while 2% Na2CO3 as an
      absorbing solution. Total cyanogen content in plum and almond kernels, as well as
      apple and flax seeds was determined.

PMID- 23871026
TI  - Beef authentication using dietary markers: chemometric selection and modelling of
      significant beef biomarkers using concatenated data from multiple analytical
      methods.
AB  - This work aimed to identify a combination of isotopic and molecular biomarkers in
      bovine muscle and adipose tissue for authentication of the diet of beef cattle.
      Muscle and adipose tissue samples were collected from animals one of four dietary
      treatments fed over a 1 year period : pasture (P), barley-based concentrate (C),
      silage followed by pasture (SiP) or silage followed by pasture with concentrate
      (SiPC). In total, 83 variables were studied including volatile compounds, colour
      and reflectance measurements, stable isotope ratios, fatty acids, beta-carotene,
      lutein and alpha-tocopherol. Chemometric models were created for each dietary
      treatment using the entire and an attenuated variable set. Meat from each dietary
      treatment was identified with a high level of accuracy (correct classification
      between 90.8% and 100%) using a discriminant approach. After elimination of
      insignificant variables, accuracy was maintained or marginally improved. SIMCA
      class-modelling performed moderately well, especially with the reduced variable
      set (76.1-100% correct classification).

PMID- 23871027
TI  - Buckwheat honeys: screening of composition and properties.
AB  - The quality of 10 buckwheat honeys, collected from Italian and est European
      beekeepers declaring to produce monofloral honey, were evaluated by means of
      their pollen, physicochemical, phenolic and volatile composition data. The
      results of the traditional analyses and in particular electrical conductivity,
      optical rotation, pH and sugar composition revealed some poorly pure samples that
      could not fit in the buckwheat tipology. Honey volatiles, analysed by solid phase
      microextraction (SPME) and gas chromatography-mass-spectrometry (GC/MS), showed
      more than 100 volatile compounds, most of them present in all honey samples but
      with quantitative variation. Besides many furfural derivates, 3-methylbutanoic
      acid was the main volatile compound found in most of honeys. Also the presence of
      2- and 3-methylbutanal and pheynalcetaldehyde confirmed the typical buckwheat
      aroma of some studied samples, corroborating physicochemical data. The HPLC
      phenolic profile was similar across the samples and p-hydroxybenzoic and p
      coumaric acids proved to be the main components. 

PMID- 23871028
TI  - Is it really organic?--multi-isotopic analysis as a tool to discriminate between
      organic and conventional plants.
AB  - Novel procedures for analytical authentication of organic plant products are
      urgently needed. Here we present the first study encompassing stable isotopes of
      hydrogen, carbon, nitrogen, oxygen, magnesium and sulphur as well as compound
      specific nitrogen and oxygen isotope analysis of nitrate for discrimination of
      organically and conventionally grown plants. The study was based on wheat,
      barley, faba bean and potato produced in rigorously controlled long-term field
      trials comprising 144 experimental plots. Nitrogen isotope analysis revealed the
      use of animal manure, but was unable to discriminate between plants that were
      fertilised with synthetic nitrogen fertilisers or green manures from atmospheric
      nitrogen fixing legumes. This limitation was bypassed using oxygen isotope
      analysis of nitrate in potato tubers, while hydrogen isotope analysis allowed
      complete discrimination of organic and conventional wheat and barley grains. It
      is concluded, that multi-isotopic analysis has the potential to disclose
      fraudulent substitutions of organic with conventionally cultivated plants. 

PMID- 23871029
TI  - Phytochemical profile of a Japanese black-purple rice.
AB  - Black-purple rice is becoming popular with health conscious food consumers. In
      the present study, the secondary metabolites in dehulled black-purple rice cv.
      Asamurasaki were analysed using HPLC-PDA-MS(2). The seeds contained a high
      concentration of seven anthocyanins (1400 MUg/g fresh weight) with cyanidin-3-O
      glucoside and peonidin-3-O-glucoside predominating. Five flavonol glycosides,
      principally quercetin-3-O-glucoside and quercetin-3-O-rutinoside, and flavones
      were detected at a total concentration of 189 MUg/g. The seeds also contained 3.9
      MUg/g of carotenoids consisting of lutein, zeaxanthin, lycopene and beta
      carotene. gamma-Oryzanol (279 MUg/g) was also present as a mixture of 24
      methylenecycloartenol ferulate, campesterol ferulate, cycloartenol ferulate and
      beta-sitosterol ferulate. No procyanidins were detected in this variety of black
      purple rice. The results demonstrate that the black-purple rice in the dehulled
      form in which it is consumed by humans contains a rich heterogeneous mixture of
      phytochemicals which may provide a basis for the potential health benefits, and
      highlights the possible use of the rice as functional food.

PMID- 23871030
TI  - Lipase-catalysed ester synthesis in solvent-free oil system: is it esterification
      or transesterification?
AB  - Ester synthesis was carried out in a solvent-free system of lipase, coconut oil
      and ethanol or fusel alcohols to ascertain the reaction mechanism. During ester
      formation, octanoic and decanoic acids increased initially and then decreased
      gradually, indicating that ester production was a two-step reaction consisting of
      hydrolysis and esterification, rather than alcoholysis. With ethanol as the
      alcohol substrate, added butyric acid inhibited ester synthesis. However, when
      fusel alcohols were used as the alcohol substrate, no significant inhibitory
      effect by butyric acid was observed. Added octanoic acid did not show any adverse
      effect on the synthesis of corresponding esters. The results suggest that
      polarity of the reactants determines lipase activity. This study provides the
      first evidence on the mechanism of immobilised lipase-catalysed ester synthesis
      in a solvent-free system involving both hydrolysis and esterification. 

PMID- 23871031
TI  - Global characterization of neutral saccharides in crude and processed Radix
      Rehmanniae by hydrophilic interaction liquid chromatography tandem electrospray
      ionization time-of-flight mass spectrometry.
AB  - The combined use of the state-of-the-art hybrid mass spectrometer (MS) together
      with high efficient liquid chromatography may prove to be a useful tool for
      neutral saccharide analysis. In the present work, we used hydrophilic interaction
      liquid chromatography (HILIC) to separate selected saccharides (fructose,
      glucose, galactose, sucrose, melibiose, raffinose, manninotriose, stachyose and
      verbascose). Influences of the column type, additive type, temperature, pH and
      other separation factors on analyte retention were evaluated. The new method did
      not require reduction, derivatization or postcolumn addition of reagents, which
      are commonly used in conventional saccharide analysis. Our results demonstrate
      the potential of HILIC-MS for sensitive and robust determination of saccharides
      in crude and processed Radix Rehmanniae, and may promote new perspectives in the
      research of other medicinal herbs. 

PMID- 23871032
TI  - Distinction between a transgenic and a conventional common bean genotype by 1H HR
      MAS NMR.
AB  - In this work, it is proposed a methodology which allows to differentiate a
      conventional and a specific transgenic common beans, grown in greenhouse or under
      field conditions, based on modifications in chemical composition using (1)H HR
      MAS NMR. It is demonstrated that the influence of typical variables from field
      planting conditions had no significant influence on the ability to set apart
      transgenic from conventional. This methodology was corroborated by multivariate
      data analysis of the (1)H NMR and IR spectra. This study also points out the
      simplicity of using the HR-MAS NMR technique for food analyses. The measurement
      is highly simplified because it does not require any pretreatment of the sample
      apart from the addition of a small amount of D2O necessary to produce homogeneous
      dough and a field frequency lock. Moreover, due to the high concentration of the
      sample, measurement time in HR-MAS NMR is very short. 

PMID- 23871033
TI  - Effect of zinc sulphate on gelling properties of phosphorylated protein isolate
      from yellow stripe trevally.
AB  - Impacts of zinc sulphate (ZnSO4) (0-140 MUmol/kg) on gel properties of yellow
      stripe trevally surimi added with sodium tripolyphosphate (STPP) (0.25% and 0.5%,
      w/w) and protein isolate phosphorylated with STPP at 0.25% and 0.5% (w/w) were
      studied. Gels from surimi added with 60 MUmol ZnSO4/kg in the absence and
      presence of 0.5% STPP had the increases in breaking force and deformation by
      20.9% and 33.3%, and 11.6% and 18.6%, respectively, compared with the control
      surimi gel (without additives). Gel of protein isolate phosphorylated with 0.5%
      STPP containing 100 MUmol ZnSO4/kg had the increases in breaking force and
      deformation by 14.87% and 5.6%, respectively, compared with the gel from non
      phosphorylated protein isolate at the same ZnSO4 level, suggesting that the
      phosphorylated protein isolate was more crosslinked by Zn(2+). The addition of
      ZnSO4 at the suitable level lowered the expressible moisture content, but
      increased whiteness of surimi or protein isolate gels (P<0.05). Non-covalent
      bonds, more likely salt bridge and ionic interactions, played a major role in
      cross-linking of proteins in both surimi and protein isolate added with ZnSO4,
      regardless of phosphates incorporated. Microstructure study revealed that a gel
      having highly interconnected and denser network with smaller voids was formed
      when protein isolate phosphorylated with 0.5% STPP was added with ZnSO4 at a
      level of 100 MUmol/kg. Thus, gel with improved properties could be obtained from
      protein isolate from yellow stripe trevally phosphorylated with STPP in
      conjunction with addition of ZnSO4 at an appropriate level.

PMID- 23871034
TI  - Characterisation of Aronia powders obtained by different drying processes.
AB  - Nowadays, food industry is facing challenges connected with the preservation of
      the highest possible quality of fruit products obtained after processing.
      Attention has been drawn to Aronia fruits due to numerous health promoting
      properties of their products. However, processing of Aronia, like other berries,
      leads to difficulties that stem from the preparation process, as well as changes
      in the composition of bioactive compounds. Consequently, in this study, Aronia
      commercial juice was subjected to different drying techniques: spray drying,
      freeze drying and vacuum drying with the temperature range of 40-80  degrees C.
      All powders obtained had a high content of total polyphenols. Powders gained by
      spray drying had the highest values which corresponded to a high content of total
      flavonoids, total monomeric anthocyanins, cyaniding-3-glucoside and total
      proanthocyanidins. Analysis of the results exhibited a correlation between
      selected bioactive compounds and their antioxidant capacity. In conclusion,
      drying techniques have an impact on selected quality parameters, and different
      drying techniques cause changes in the content of bioactives analysed. Spray
      drying can be recommended for preservation of bioactives in Aronia products.
      Powder quality depends mainly on the process applied and parameters chosen.
      Therefore, Aronia powders production should be adapted to the requirements and
      design of the final product.

PMID- 23871035
TI  - Carotenoid profiling in tubers of different potato (Solanum sp) cultivars:
      accumulation of carotenoids mediated by xanthophyll esterification.
AB  - The carotenoid profile of sixty potato cultivars (commercial, bred, old and
      native cultivars) has been characterised in order to provide information to be
      used in selective breeding programs directed to improve the nutritional value of
      this important staple food. Cultivars were segregated into three groups according
      to the major pigment in the carotenoid profile: violaxanthin (37 cultivars;
      especially those with higher carotenoid content), lutein (16 cultivars), and
      neoxanthin (7 cultivars). Other minor carotenoids were antheraxanthin, beta
      cryptoxanthin and beta-carotene, while zeaxanthin was absent in all sample. The
      total carotenoid content ranged from 50.0 to 1552.0 MUg/100 g dry wt, with an
      average value of about 435.3 MUg/100 g dry wt. Sipancachi, Poluya and Chaucha
      native cultivars showed the highest carotenoid content (1020.0, 1478.2 and 1551.2
      MUg/100 g dry wt, respectively). Xanthophyll esters were present in most
      cultivars, mainly as diesterified forms, being observed a direct correlation
      between the carotenoid content and the esterified fraction, suggesting that the
      esterification process facilitates the accumulation of these lipophilic compounds
      within the plastids. Therefore, the presence of xanthophyll esters should be a
      phenotypic character to be included in the breeding studies, and more efforts
      should be dedicated to the understanding of the biochemical process leading to
      this structural modification of carotenoids in plants.

PMID- 23871036
TI  - Isolation, purification and identification of nine chemical compounds from
      Flammulina velutipes fruiting bodies.
AB  - This study was designed to isolate and characterise Flammulina velutipes fruiting
      body chemical constituents and to find marker compound(s) suitable for processed
      mushroom products quality control. Extracts were prepared by soaking F. velutipes
      powdered fruiting bodies in 95% ethanol at 25  degrees C for 24 h; repeated three
      times; followed by concentrating under reduced pressure at 40  degrees C; and
      purifying using consecutive chromatographic methods. The compound structures were
      determined using spectral data analysis and comparing with literature values.
      Nine chemical constituents: D-arabinitol (1), 9(Z) oleic acid (2), 9(Z),12(Z)
      linoleic acid (3), ergosta-5,7,22-trien-3beta-ol (4), 5alpha,8alpha-epidioxy
      ergosta-6,22-dien-3beta-ol (5), 3beta,5alpha,9alpha-trihydroxy-ergosta-7,22-dien
      6-one (6), 5-hydroxymethyl-2-(1-methyl-ethenyl)-1-cyclohexanol (7), 1,3
      dilinolein (8) and hemisceramide (9), were isolated and identified. Compound 7 is
      a new monoterpene not previously reported. For the first reported time, compound
      9 was isolated from the fruiting bodies. It was also found that D-arabinitol may
      serve as the marker compound for processed golden needle mushroom products
      quality control.

PMID- 23871037
TI  - Bound phytophenols from ready-to-eat cereals: comparison with other plant-based
      foods.
AB  - Whole-grain diets are linked to reduced risk of several chronic diseases (heart
      disease, cancer, diabetes, metabolic syndrome) and all-cause mortality. There is
      increasing evidence that these benefits are associated with the gut microbiota
      and that release of fibre-related phenolic metabolites in the gut is a
      contributing factor. Additional sources of these metabolites include fruits and
      vegetables, but the evidence for their protective effects is less well
      established. With respect to the availability of bound phytophenols, ready-to-eat
      cereals are compared with soft fruits (considered rich in antioxidants) and other
      commonly consumed fruits and vegetables. The results demonstrated that when
      compared with an equivalent serving of fruits or vegetables, a recommended
      portion of whole-grain cereals deliver substantially higher amounts of bound
      phytophenols, which are available for metabolism in the colon. The increased
      amount of these phenolic metabolites may, in part, explain the evidence for the
      protective effects of whole-grain cereals. 

PMID- 23871038
TI  - Effect of artificial ageing using different wood chips on the antioxidant
      activity, resveratrol and catechin concentration, sensory properties and colour
      of two Greek red wines.
AB  - Two Greek red wines (Syrah and Cabernet) were artificially aged with different
      wood chips (white oak, red oak, Turkey oak, chestnut, Bosnian pine, cherry,
      common juniper, common walnut, white mulberry, black locust and apricot). The
      influence of each wood species was tested for up to 20 days. The optimum duration
      for the extraction of total polyphenols was 20 days (Syrah) or 10 days (Cabernet)
      when chips of white oak, chestnut, cherry, white mulberry, black locust and
      apricot where used. Resveratrol and catechin concentrations ranged within the
      limits previously reported in literature. A high antioxidant activity was
      established after 10 days of artificial ageing. The sensory evaluation showed
      that the best results were produced by the apricot chips after 5 days (Syrah) or
      black locust and apricot after 5 days (Cabernet). Colour was seen to increase
      with both time of ageing and number of wood chips added.

PMID- 23871039
TI  - Regulation of lipid and glucose homeostasis by mango tree leaf extract is
      mediated by AMPK and PI3K/AKT signaling pathways.
AB  - Ethanolic extract of Mangifera indica (mango) dose-dependently decreased serum
      glucose and triglyceride in KK-A(y) mice. Our in vitro and in vivo investigations
      revealed that the effect of mango leave extract (ME) on glucose and lipid
      homeostasis is mediated, at least in part, through the PI3K/AKT and AMPK
      signaling pathway. ME up-regulated the expression of PI3K, AKT and GYS genes by
      2.0-fold, 3.2-fold, and 2.7-fold, respectively, leading to a decrease in glucose
      level. On the other hand, ME up-regulated AMPK and altered lipid metabolism. ME
      also down-regulated ACC (2.8-fold), HSL (1.6-fold), FAS (1.8-fold) and PPAR-gamma
      (4.0-fold). Finally, we determined that active metabolites of benzophenone C
      glucosides, Iriflophenone 3-C-beta-glucoside and Foliamangiferoside A from ME,
      may play a dominant role in this integrated regulation of sugar and lipid
      homeostasis. 

PMID- 23871040
TI  - Analytical characterisation of Negroamaro red wines by "Aroma Wheels".
AB  - In this work we characterised Negroamaro red wines, made by an autochthonous
      cultivar of Southern Italy, by linking volatile composition to aroma properties.
      This linking was carried out by picturing "Aroma Wheels", built by Odour Activity
      Values (OAVs) of all the identified volatile compounds grouped in "aromatic
      series" belonging to 13 classes of sensory descriptors. The 18 most active
      odorants with OAV>1 were mainly alcohols, fatty acids and their ethyl esters. The
      "OAVs' Aroma Wheels" showed that the classes of sensory descriptors are first
      fruity and floral, next fatty and pungent and minor nutty and caramelised notes.
      Principal Component Analysis displayed correlations between sensory descriptors
      and wine samples; the main 7-fruity and 5-floral sensory features of Negroamaro
      wines have negative values of PC1 and they are negatively correlated with the
      second main sensory feature, i.e. 13-fatty, falling at positive value of PC1;
      this fit the aroma perception of this varietal.

PMID- 23871041
TI  - A sorghum xylanase inhibitor-like protein with highly potent antifungal,
      antitumor and HIV-1 reverse transcriptase inhibitory activities.
AB  - A 25-kDa protein, with an N-terminal amino acid sequence homologous to that of
      xylanase inhibitor and designated as xylanase inbibitor-like protein (XILP) was
      purified from sorghum seeds. The isolation protocol consisted of affinity
      chromatography, ion exchange chromatography, and gel filtration. XILP inhibited
      mycelial growth in various phytopathogenic fungi. The antifungal activity was
      thermostable and pH-stable. XILP inhibited proliferation of various cancer cell
      lines but did not do so in human embryonic liver (WRL 68) cells. There was no
      mitogenic activity toward mouse splenocytes. XILP reduced the activity of HIV-1
      reverse transcriptase with an IC50 of 11.1MUM, but lacked inhibitory activity
      toward HIV-1 integrase and SARS coronavirus proteinase. In conclusion, sorghum
      XILP is thermostable and pH stable and exhibits potent antifungal,
      antiproliferative, and HIV-1 reverse transcriptase inhibitory activities. 

PMID- 23871042
TI  - Antioxidant and antiproliferative properties of methylated metabolites of
      anthocyanins.
AB  - Anthocyanins are major flavonoids in many plant foods and have been related to
      health promotion. In the human organism anthocyanins are metabolised to different
      metabolites. One of the most important phase II reactions of flavonoids is the
      methylation of the catechol group. This feature is expected to have an effect on
      the antioxidant and antiproliferative properties of flavonoids including
      anthocyanins. In this work, delphinidin-3-glucoside, cyanidin-3-glucoside and
      petunidin-3-glucoside methylated metabolites were obtained by enzymatic hemi
      synthesis. The compounds were identified as monomethylated products by HPLC-MS
      and NMR. The methylated metabolites were found to still retain significant
      radical scavenging activity and reducing activity, suggesting that they could act
      as potential antioxidants in vivo. The antiproliferative activity of the
      metabolites in comparison with the parental anthocyanins was also evaluated in
      three cancer cell lines by sulforhodamine B assay. The conjugation with methyl
      groups decreased or did not alter the antiproliferative effect of the original
      anthocyanin. 

PMID- 23871043
TI  - Formation of solid shell nanoparticles with liquid omega-3 fatty acid core.
AB  - A major challenge for food and pharmaceutical industries is the engineering of
      nanostructures that can efficiently encapsulate bioactive compounds with enhanced
      physical and chemical stability, and high load. The influence of surfactant
      properties on the physical and chemical stability of (i) nanostructured lipid
      carriers (NLC) containing tristearin and omega-3 fish oil, (ii) tristearin solid
      lipid nanoparticles (SLN), and (iii) omega-3 fish oil-in-water emulsions was
      investigated. As surfactants we used low (LM)- and high-melting (HM) lecithins.
      Results indicated that the presence of fish oil reduced the crystallisation
      temperature, melting temperature, and melting enthalpy of tristearin. NLC
      stabilized with HM-lecithin inhibited the oxidation of omega-3 fatty acids >=90%
      compared to those stabilized with LM-lecithin. This was attributed to the
      solidified surfactant layer of HM-lecithin inducing crystallisation of the shell
      by interfacial heterogeneous nucleation. The results showed that the saturated HM
      lecithin was the key in controlling the crystallisation behaviour, and thereby
      enabled the formation of oxidatively and physically stable lipid nanoparticles.

PMID- 23871044
TI  - Simultaneous production of multi-functional peptides by pancreatic hydrolysis of
      bovine casein in an enzymatic membrane reactor via combinational chromatography.
AB  - Three bioactive peptides, angiotensin-converting enzyme-inhibitory peptides
      (ACEIPs), casein phosphopeptides (CPPs) and antimicrobial peptides (AMPs), were
      simultaneously prepared from casein by pancreatic hydrolysis via an enzymatic
      membrane reactor (EMR) and combinational chromatography. The reaction was
      performed at 37  degrees C and pH 8.0 for 3h followed by ultrafiltration. ACEIPs
      were purified by size exclusion chromatography (SEC) from permeate fractions with
      molecular weight (MW) below 1 kDa. Concurrently, strong cation exchange high
      performance liquid chromatography (SCE-HPLC) was used to isolate CPPs and AMPs
      from retentate fractions ranging from 1 kDa and 5 kDa. Following reverse-phase
      high performance liquid chromatography-electrospray ionization tandem mass
      spectrometry (RP-HPLC-ESI-MS/MS) analysis, potential ACEIPs and a total of 34
      CPPs were identified (18 corresponded to alphas1-casein, 2 to alphas2-casein, 10
      to beta-casein and 4 to kappa-casein). Additionally, the ACEIPs in fraction B
      from SEC had the highest ACE-inhibiting-activity (73.5% in 1.0mg/ml), while total
      concentrations of AMPs were directly proportional to overall antibacterial
      activity. Uniquely, fraction 5 from SCE exhibited the highest activity against
      Staphylococcus aureus (97.49% in 1.0 mg/ml).

PMID- 23871045
TI  - Formation of complex natural flavours by biotransformation of apple pomace with
      basidiomycetes.
AB  - Altogether 30 different basidiomycetes were grown submerged in liquid culture
      media using seven different by-products of the food industry as the only carbon
      source. Seven fungus/substrate combinations revealed interesting flavour
      profiles. Culture supernatants of Tyromyces chioneus grown on apple pomace were
      extracted, and the aroma compounds were analysed by gas chromatography
      olfactometry (GC-O). Potent odorants were identified by aroma extract dilution
      analysis (AEDA), calculation of the odour activity values (OAV), and proven by
      confection of an aroma model. 3-Phenylpropanal, 3-phenyl-1-propanol, and benzyl
      alcohol were identified as potent aroma biotransformation products. Headspace
      solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS)
      experiments showed that 3-phenylpropanal, 3-phenyl-1-propanol, benzyl alcohol,
      methyl 3-phenylpropionate, methyl 2-phenylacetate, cinnamaldehyde and methyl
      cinnamate were produced during the cultivation period of eight days. By means of
      labelling experiments, (E)-cinnamic acid was identified as the precursor of 3
      phenylpropanal and 3-phenyl-1-propanol. Basidiomycetes were able to biotransform
      food by-products to pleasant complex flavour mixtures. 

PMID- 23871046
TI  - The quality of protein of coloured fleshed potatoes.
AB  - Potatoes of purple varieties and red flesh colour were estimated as the important
      food product containing valuable protein. Amino acids concentration and protein
      nutritive value of coloured potatoes were analysed and compared with traditional
      yellow-fleshed varieties. Studies comprised potatoes of 13 varieties: 7 of purple
      fleshed, four of red-fleshed and two of yellow-fleshed. There were observed
      differences between studied potatoes with respect to dry matter, starch and
      protein content as well as to amino acids concentration and protein quality
      independently on flesh colour. Potatoes of low as well of high content of total
      protein, independently on flesh colour, characterised similar protein quality,
      like for example varieties of Blaue Anneliese and Highland B. Red or Blue Congo
      and Salad Blue. Leucine limited the quality of majority of coloured fleshed
      potato varieties used for the experiment. The best amino acid profiles and
      protein quality confirmed by chemical scores and EAA index values characterised
      purple fleshed Vitelotte and Blaue Anneliese, yellow fleshed Verdi as well as red
      fleshed Herbie 26, Highland B. Red and Rosemarie. 

PMID- 23871047
TI  - What are the ideal properties for functional food peptides with antihypertensive
      effect? A computational peptidology approach.
AB  - Peptides with antihypertensive potency have long been attractive to the medical
      and food communities. However, serving as food additives, rather than therapeutic
      agents, peptides should have a good taste. In the present study, we explore the
      intrinsic relationship between the angiotensin I-converting enzyme (ACE)
      inhibition and bitterness of short peptides in the framework of computational
      peptidology, attempting to find out the appropriate properties for functional
      food peptides with satisfactory bioactivities. As might be expected, quantitative
      structure-activity relationship modeling reveals a significant positive
      correlation between the ACE inhibition and bitterness of dipeptides, but this
      correlation is quite modest for tripeptides and, particularly, tetrapeptides.
      Moreover, quantum mechanics/molecular mechanics analysis of the structural basis
      and energetic profile involved in ACE-peptide complexes unravels that peptides of
      up to 4 amino acids long are sufficient to have efficient binding to ACE, and
      more additional residues do not bring with substantial enhance in their ACE
      binding affinity and, thus, antihypertensive capability. All of above, it is
      coming together to suggest that the tripeptides and tetrapeptides could be
      considered as ideal candidates for seeking potential functional food additives
      with both high antihypertensive activity and low bitterness. 

PMID- 23871048
TI  - High-yield production of a low-temperature-active polygalacturonase for papaya
      juice clarification.
AB  - A novel endo-polygalacturonase (endo-PG I) from Achaetomium sp. Xz8 was
      identified, overexpressed in Pichia pastoris, and characterized in this report.
      Recombinant endo-PG I is distinguished from other enzyme counterparts by its high
      activity towards polygalacturonic acid (49,934 U/ml) and high yield in the 15-l
      fermentor (2.13 g/l). It exhibits optimal activity at 45  degrees C and remained
      active over a broad temperature range of 0-80  degrees C. Distinct from most
      fungal polygalacturonases that have acidic pH optima, endo-PG I is optimally
      active at pH 6, similar to the pH of fresh papaya juice (5.7). Endo-PG I alone
      reduced the viscosity of papaya juice by 17.6%, and increased its transmittance
      by 59.1%. When combined with a commercial pectin methylesterase, it showed much
      higher efficiency with a synergy degree of more than 1.25. All these favourable
      enzymatic properties make endo-PG I attractive for potential applications in the
      juice industry.

PMID- 23871049
TI  - Isolation of the four methyl jasmonate stereoisomers and their effects on
      selected chiral volatile compounds in red raspberries.
AB  - The four stereoisomers present in a commercial sample of methyl jasmonate (MJ)
      were isolated at semi-preparative scale by HPLC, using a permethylated beta
      cyclodextrin column. This allowed the baseline resolution and collection of both
      major (methyl jasmonates) and minor (epi-methyl jasmonates) stereoisomers. When
      1.5 mL of a 5mg per mL MJ solution were injected, isolated amounts were 3.56 mg
      for (-) and (+)-methyl jasmonates, with respective purities of 96.1% and 99.9%,
      and 0.18 mg for (-)- and (+)-epi-methyl jasmonates, with 98.6% and 91.6%
      respective purities. The post-harvest treatment of red raspberry fruits with the
      pure methyl jasmonate stereoisomers isolated proved that (-)-epi-MJ either
      promotes the bioformation of (+)-limonene or inhibits that of (-)-limonene to a
      greater extent than the other three MJ stereoisomers, while the biosynthesis of
      the (+)-enantiomer of alpha-ionone is favoured equally, whichever MJ stereoisomer
      used. The results obtained in the present study might be used to obtain food
      products with improved sensory characteristics.

PMID- 23871050
TI  - Variation and correlation analysis of phenolic compounds in mungbean (Vigna
      radiata L.) varieties.
AB  - Phenolic compounds from a wide collection of mungbean [Vigna radiata (L.)
      Wilczek] germplasm (56 varieties) were characterised to determine the diversity
      among these phytochemicals and to analyse the relationships among their contents.
      The profiles of 25 phenolic compounds identified from the grains were subjected
      to data-mining processes, including principal component analysis (PCA), partial
      least squares discriminant analysis (PLS-DA), Pearson's correlation analysis, and
      hierarchical clustering analysis (HCA). The IT212105 and IT104818 varieties
      separated from the others in the first two principal components of PCA. PLS-DA
      showed significant separation between extracts of mungbean originating from three
      countries: China, Japan, and Korea. HCA of these phytochemicals resulted in
      clusters derived from common or closely related biochemical pathways. Significant
      positive relationships were observed between coumaric acid and resveratrol
      (r=0.7195, p<0.0001). Catechin content was positively correlated with rutin
      (r=0.6291, p<0.0001). The IT104818 variety appears to be a good candidate for
      future breeding programs, as it contains high levels of phenolic compounds. These
      results demonstrate the use of metabolic profiling combined with chemometrics as
      a tool for assessing the quality of food. 

PMID- 23871051
TI  - Stabilisation of strawberry (Fragaria x ananassa Duch.) anthocyanins by different
      pectins.
AB  - The objective of the present study was to evaluate the effects of different
      pectins on strawberry anthocyanins in viscous model solutions at pH 3.0. For this
      purpose, low esterified amidated, low and high methyl esterified citrus and apple
      pectins, and a sugar beet pectin (SBP), respectively, were added to strawberry
      extracts. The latter were predominantly composed of pelargonidin-glycosides,
      containing either reduced (E-1) or original amounts of non-anthocyanin phenolics
      (E-2). Model systems were stored for 18 weeks at 20+/-0.5  degrees C protected
      from light, and anthocyanins were quantitated in regular intervals by HPLC-DAD
      analyses. Half-life (t1/2) and destruction (D) values were calculated based on
      first-order kinetics. Generally, significant differences in pigment retention
      could be ascribed to differing pectin sources, while variation in the degree of
      esterification and amidation, respectively, had negligible effects. Compared to
      systems without added pectin, apple pectins and SPB enhanced anthocyanin
      stability moderately, while stabilising effects of citrus pectins were poor or
      even imperceptible. Generally, the amount of non-anthocyanin phenolics and the
      addition of citrate did not markedly affect anthocyanin stability. However,
      pectins had no influence on total phenolic contents (Folin-Ciocalteu assay) and
      antioxidant capacities (FRAP and TEAC assay) of strawberry phenolics over time.
      For pelargonidin-3-glucoside and -rutinoside largely consistent stabilities were
      found in all model systems. In contrast, pelargonidin-3-malonylglucoside was less
      stable in the blank, and stabilisation by pectins was always negligible. The
      findings of the present study are contrary to results reported previously for the
      stabilisation of cyanidin- and delphinidin-glycosides in similar model systems
      prepared with black currant extracts, indicating a high impact of the number of
      hydroxyl groups in the anthocyanin B-ring.

PMID- 23871052
TI  - Physico-chemical properties of different forms of bovine lactoferrin.
AB  - Three forms of bovine lactoferrin (Lf), apo-, native- and holo- with 0.9%, 12.9%
      and 99.7% iron content, respectively, were characterised for their physico
      chemical properties. Colour, surface tension, thermal properties, particle charge
      and rheological behaviour of Lf were found to be affected by the form of Lf. The
      surface tension of Lf tends to decrease with decrease in iron content. The
      Circular Dichroism (CD) spectra confirmed that all forms of Lf had similar
      secondary structures while the tertiary structure was different for holo-Lf. The
      Differential Scanning Calorimeter (DSC) analysis showed that the apo- and holo-Lf
      in aqueous solution displayed thermal denaturation temperatures of 71+/-0.2 and
      91+/-0.5  degrees C, respectively, suggesting that the iron saturation of Lf
      tends to increase its thermal stability. The study of particle charge properties
      (zeta-potential) in 1 mM KCl salt solution showed that apo-Lf reached the net
      charge of zero in the pH range 5.5-6.5 whereas native and holo-Lf in the pH range
      8.0-9.0. The apparent viscosity of 1% (wt/wt) solution of the different forms of
      Lf showed no difference between apo- and native-Lf (~1.4 mPas) while the value
      was significantly higher (2.38 mPas) for holo-Lf.

PMID- 23871053
TI  - Concentrations of Cd, Cu, Pb and Zn in soft tissue of oyster (Saccostrea
      cucullata) collected from the Lengeh Port coast, Persian Gulf, Iran: a comparison
      with the permissible limits for public health.
AB  - This study examines concentrations of Cd, Cu, Pb and Zn in the soft tissue of
      Saccostrea cucullata in the intertidal zones of Lengeh Port, Persian Gulf, Iran,
      to survey whether heavy metals are within the acceptable limits for public
      health? The results revealed that the average metal concentrations (MUg/g dry
      weight) ranged from 10.28 to 12.03 for Cd, 294.10 to 345.80 for Cu, 20.64 to
      58.23 for Pb and 735.60 to 760.40 for Zn in the soft tissue of oysters. From the
      human public health point of view, comparison between the mean concentrations of
      the metals in the soft tissue of oyster and global guidelines clearly indicates
      that nearly in all cases concentrations are higher than the permissible amounts
      for human consumption. In addition, levels of Zn, Pb and Cu were well below their
      recommended oral maximum residue level (MRLs), whereas levels of Cd were observed
      two times higher. 

PMID- 23871054
TI  - Hepatoprotective effects of eburicoic acid and dehydroeburicoic acid from
      Antrodia camphorata in a mouse model of acute hepatic injury.
AB  - The hepatoprotective effects of eburicoic acid (TR1) and dehydroeburicoic acid
      (TR2) from Antrodia camphorata (AC) against carbon tetrachloride (CCl4)-induced
      liver damage were investigated in mice. TR1 and TR2 was administered
      intraperitoneally (i.p.) for 7 days prior to the administration of CCl4.
      Pretreatment with TR1 and TR2 prevented the elevation of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), and liver lipid peroxides
      in CCl4-treated mice. The activities of antioxidant enzymes [catalase (CAT),
      superoxide dismutase (SOD), and glutathione peroxidase (GPx)], nitric oxide (NO)
      production, and tumour necrosis factor-alpha (TNF-alpha) were decreased after the
      treatment with TR1 and TR2 in CCl4-treated mice. Western blotting revealed that
      TR1 and TR2 significantly decreased inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) expressions and increased the expression of cytochrome
      P4502E1 (CYP2E1) in CCl4-treated mice. Therefore, we speculate that TR1 and TR2
      protect the liver from CCl4-induced hepatic damage via antioxidant and anti
      inflammatory mechanisms.

PMID- 23871055
TI  - Non-targeted 1H NMR fingerprinting and multivariate statistical analyses for the
      characterisation of the geographical origin of Italian sweet cherries.
AB  - In this study, non-targeted (1)H NMR fingerprinting was used in combination with
      multivariate statistical techniques for the classification of Italian sweet
      cherries based on their different geographical origins (Emilia Romagna and
      Puglia). As classification techniques, Soft Independent Modelling of Class
      Analogy (SIMCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Linear
      Discriminant Analysis (LDA) were carried out and the results were compared. For
      LDA, before performing a refined selection of the number/combination of
      variables, two different strategies for a preliminary reduction of the variable
      number were tested. The best average recognition and CV prediction abilities
      (both 100.0%) were obtained for all the LDA models, although PLS-DA also showed
      remarkable performances (94.6%). All the statistical models were validated by
      observing the prediction abilities with respect to an external set of cherry
      samples. The best result (94.9%) was obtained with LDA by performing a best
      subset selection procedure on a set of 30 principal components previously
      selected by a stepwise decorrelation. The metabolites that mostly contributed to
      the classification performances of such LDA model, were found to be malate,
      glucose, fructose, glutamine and succinate. 

PMID- 23871056
TI  - Optimisation of aqueous two-phase extraction of anthocyanins from purple sweet
      potatoes by response surface methodology.
AB  - Aqueous two-phase extraction (ATPE) method was investigated for extraction of
      anthocyanins from purple sweet potatoes using response surface methodology (RSM).
      Results showed that the optimal conditions for anthocyanin extraction were that,
      45:1 (mL/g) liquid-solid ratio, 25% (W/W) ethanol, 22% (W/W) concentration of
      ammonium sulphate and pH3.3; the anthocyanin yield and partition coefficient
      under the optimal conditions were 90.02% and 19.62, respectively. The result of
      HPLC-ESI-MS analysis revealed eight kinds of compounds, and the major
      anthocyanins as cyanidi-caffeoy-fumaroy-sophoroside-3-O-glucoside, peonidin
      caffeoyl-hydroxybenzoyl-3-O-glucoside, peonidin-caffeoyl-sophoroside-3-O
      glucoside, and peonidin-caffeoyl-fumaroyl-sophorosid-3-O-glucoside. Meanwhile, we
      found a compound as a dimer of galloyl procyanin. These results suggest that ATPE
      is efficient in extracting anthocyanins and has the potential to be used in
      natural anthocyanin extraction industry.

PMID- 23871057
TI  - A study of the antioxidant properties of beers using electron paramagnetic
      resonance.
AB  - The antioxidant properties of various kinds of beers were investigated using
      electron paramagnetic resonance (EPR) spectroscopy. This was possible by
      measuring the changes in the intensity of the EPR spectrum that resulted from the
      interaction of the stable radical DPPH (1,1-diphenyl-2-picrylhydrazyl) with the
      antioxidants found in a beer sample. The antioxidant capacity was then presented
      in Trolox Equivalents, e.g. MUM trolox in a beer sample of 100ml. The influence
      of the type, colour, the content of the extract and alcohol on the antioxidant
      activities of commercial beer samples was investigated using two-way hierarchical
      clustering and analysis of variance. The results showed that all of the beers
      investigated exhibit antioxidant properties. By performing an analysis of
      variance, it was found that the value of the antioxidant capacity significantly
      (0.05 level of significance) depends on the content of the extract and the colour
      of the beer. It seems that additives also influence the antioxidant properties to
      some extent, but neither the alcohol content nor the kind of fermentation affects
      the antioxidant properties of beer. 

PMID- 23871058
TI  - Microstructure characterization of a food-grade U-type microemulsion system by
      differential scanning calorimetry and electrical conductivity techniques.
AB  - The microstructure transitions of a food-grade U-type microemulsion system
      containing glycerol monolaurate and propionic acid at a 1:1 mass ratio as oil
      phase and Tween 80 as surfactant were investigated along a water dilution line at
      a ratio of 80:20 mass% surfactant/oil phase, based on a previously studied phase
      diagram. From the water thermal behaviours detected by differential scanning
      calorimetry, three structural regions are identified along the dilution line. In
      the first region, all water molecules are confined to the water core of the
      reverse micelles, leading to the formation of w/o microemulsion. As the water
      content increases, the water gains mobility, transforms into bicontinuous in the
      second region, and finally the microemulsion become o/w in the third region. The
      thermal transition points coincide with the structural phase transitions by
      electrical conductivity measurements, indicating that the structural transitions
      occur at 35 and 65 mass% of water along the dilution line.

PMID- 23871059
TI  - Regulating the secondary metabolism in grape berry using exogenous 24
      epibrassinolide for enhanced phenolics content and antioxidant capacity.
AB  - The objective of this study is to investigate the influence of application of
      exogenous 24-epibrassinolide (EBR) on the antioxidant capacity, anthocyanins and
      phenolics content of Vitis vinifera grape berry (cvs. Yan 73 and Cabernet
      Sauvignon). The grapevine clusters were sprayed with 0 (control), 0.10, 0.40, or
      0.80 mg/l of 24-epibrassinolide during veraison, respectively. The EBR
      application increased the activities of phenylalanine ammonia-lyase (PAL) and UDP
      glucose: flavonoid 3-O-glucosyltransferase (UFGT), the content of total
      phenolics, tannins, flavonoids and anthocyanins, individual anthocyanins and the
      antioxidant capacity of matured grape skins in both varieties. The application
      also increased the content of flavonoids and anthocyanins in Yan73 pulp. Compared
      to the other treatments, the treatment of EBR at 0.40 mg/l had significantly
      higher level than the control in all above assays. Our results indicated that the
      exogenous EBR treatment can significantly promote grape ripening and enhance
      anthocyanins and other phenolics contents and antioxidant capacity in the grape
      skin.

PMID- 23871060
TI  - Rapid detection of melamine adulteration in dairy milk by SB-ATR-Fourier
      transform infrared spectroscopy.
AB  - Melamine is a nitrogenous chemical substance used principally as a starting
      material for the manufacture of synthetic resins. Due to its very high proportion
      of nitrogen melamine has been added illegitimately to foods and feeds to increase
      the measured protein content, which determines the value of the product. These
      issues prompted private as well as governmental laboratories to develop methods
      for the analysis of melamine in a wide variety of food products and ingredients.
      Owing to this fact present study is aimed to use single bounce attenuated total
      reflectance (SB-ATR) Fourier transform infrared spectroscopy (FTIR) method as an
      effective rapid tool for the detection and quantification of melamine in milk
      (liquid and powder). Partial least-squares (PLS) models were established for
      correlating spectral data to melamine concentration with R(2)>0.99, and RMSEC
      0.370. Linear calibration curves were obtained over the calibration range of 25
      0.0625%. The LOD and LOQ of the method was 0.00025% (2.5 ppm) and 0.0015% (15
      ppm) respectively. Proposed SB-ATR-FTIR method requires little or no sample
      preparation with an assay time of 1-2 min.

PMID- 23871061
TI  - Enhanced production of gamma-cyclodextrin by optimization of reaction of gamma
      cyclodextrin glycosyltransferase as well as synchronous use of isoamylase.
AB  - In this study, we examined the production of gamma-cyclodextrin (gamma-CD) using
      gamma-cyclodextrin glycosyltransferase (gamma-CGTase) from Bacillus clarkii 7364.
      We investigated a variety of factors that affect the yield of gamma-CD, including
      key factors such as solvent, substrate, temperature, pH, enzyme dosage. After
      optimising the reaction parameters, a 50.4% (w/w) yield of gamma-CD was obtained
      with 15% (w/v) potato starch and cyclododecanone (which could be easily removed).
      In order to further enhance the production of gamma-CD, we constructed the gamma
      CGTase mutant A223K by site-directed mutagenesis, and used it synchronously with
      the isoamylase obtained from Thermobifida fusca. At pH 7.0 and 50  degrees C,
      72.5% (w/w) gamma-CD yield was achieved after 10h, which was 22.1% higher than
      that obtained using gamma-CGTase alone, and represents the highest yield reported
      to date. The substantially higher yield and selectivity of gamma-CD obtained in
      the present study provides the basis for the industrial-scale production of gamma
      CD.

PMID- 23871062
TI  - Pro-oxidant/antioxidant behaviours of ascorbic acid, tocopherol, and plant
      extracts in n-3 highly unsaturated fatty acid rich oil-in-water emulsions.
AB  - This study investigated the oxidative stability of n-3 highly unsaturated fatty
      acid (n-3 HUFA) rich (35% n-3 HUFA) oil-in-water emulsions (10 wt% oil) with
      commercial antioxidants and natural plant extracts. Ascorbic acid, alpha
      tocopherol, and the extracts of Indian gooseberry fruit (Emblica officinalis)
      (IGFE) and sweet basil leaves (Ocimum basilicum L.) (SBLE) were used for the
      study as antioxidants. The progress of oxidation in the systems was evaluated at
      35  degrees C over 120 h against a control (without antioxidant) by monitoring
      the formation of primary (conjugated dienes) and secondary (volatile carbonyl
      compounds) oxidation products. Volatile carbonyl compounds were trapped as
      derivatives of pentafluorophenyl hydrazine and quantified by headspace solid
      phase microextraction analysis. About 40 volatile carbonyls were successfully
      identified by this method. trans,trans-2,4-Heptadienal, trans,cis-2,4
      heptadienal, 3,5-octadien-2-one, and 1-penten-3-ol were predominant. The volatile
      carbonyl compounds and conjugated dienes were formed at low rates in emulsion
      systems in which alpha-tocopherol and natural plant extracts had been introduced,
      compared to the control. Emulsion systems containing ascorbic acid showed low
      stability, as indicated by the oxidation products that were formed at high rates
      compared to the control. These results indicated that ascorbic acid activated the
      oxidation reactions in n-3 HUFA rich water emulsions, while natural plant
      extracts that were rich in polyphenols and alpha-tocopherol were active as
      antioxidants. The present study further demonstrated the applicability of the
      polar paradox theory in the determination of stability for n-3 HUFA rich water
      emulsions with commercial antioxidants and natural plant extracts.

PMID- 23871063
TI  - Synthesis and characterisation of galactosyl glycerol by beta-galactosidase
      catalysed reverse hydrolysis of galactose and glycerol.
AB  - A study of an enzymatic method for the production of galactosylglycerol is
      described. The effects of enzyme sources, enzyme amount, reaction temperature,
      reaction time, substrate ratio of glycerol to galactose, buffer content and pH on
      galactosylglycerol yield (mg/ml) were investigated. Under the optimum reaction
      conditions of beta-galactosidases from Kluyveromyces lactis 240 U/ml, temperature
      40  degrees C, time 24 h, buffer amount 60% (percent volume of buffer to that of
      substrates, pH 6.5), and the substrate molar ratio of 10 (glycerol16
      mmol:galactose 1.6 mmol), the yield of galactosylglycerol was up to 116.47 mg/ml
      (galactose conversion 55.88%). The product was purified by activated charcoal and
      Sephadex G-15 column chromatography, up to 96%. The purified galactosylglycerol
      was fully characterised by MS and NMR, and identified as a mixture of (2R)- and
      (2S)- 3-O-beta-D-galactopyranosyl-glycerol.

PMID- 23871064
TI  - Determination and identification of hydrophilic and hydrophobic arsenic species
      in methanol extract of fresh cod liver by RP-HPLC with simultaneous ICP-MS and
      ESI-Q-TOF-MS detection.
AB  - The present study was focused on the determination and identification of arsenic
      species in methanolic extracts of cod liver. Arsenic species were fractionated
      and the fractions analysed by RP-HPLC-ICP-MS coupled with ESI-Q-TOF-MS. The total
      concentration of arsenic in the fresh cod liver was analysed by ICP-MS to be
      1.53+/-0.02 mg As kg(-1)w.w. and the extraction recovery was ca. 100% and the
      column recovery >93%. Besides polar inorganic and methylated arsenic species
      (>70%) more hydrophobic arsenic-containing fatty acids and hydrocarbons occurred.
      Based on the mass spectrometric data proposals for molecular structures were
      elaborated for 20 of the organic As species included 10 arsenic-containing fatty
      acids (AsFA) and an arsenic-containing hydrocarbon (AsHC) mentioned for the first
      time in fresh cod liver. Arsenobetaine was found as main water-soluble arsenic
      compound in cod liver followed by higher molecular mass arsenic-containing fatty
      acids and hydrocarbons.

PMID- 23871065
TI  - Authentication of lotus root powder adulterated with potato starch and/or sweet
      potato starch using Fourier transform mid-infrared spectroscopy.
AB  - Fourier transform mid infrared (FT-MIR) spectroscopy combined with chemometrics
      techniques were developed for classification and quantification of cheaper
      starches (potato and sweet potato starch) in lotus root powder (LRP). By
      performing principal component analysis (PCA), it was possible to distinguish
      between adulterated and non-adulterated LRP. The coefficient of determination
      (R(2)) and standard deviation ratio (SDR) of calibration set were found to be
      0.9587-0.9898 and 3.63-10.2, depending on the pre-treatment of spectra. The
      external validation set gave a coefficient of determination (R(2)) and standard
      deviation ratio (SDR) of 0.9810 and 5.47, respectively. Moreover, the limit of
      detection (1%), the limit of quantification (3%), reasonable recovery (92.3
      101.5%), satisfactory intra-assay (2.9-5.5%) and inter-assay (11.0-13.5%)
      precision illustrated the good performance of the present method. The results
      obtained in this study indicate that FT-MIR spectroscopy can be used as an easy,
      rapid and novel tool to detect the LRP adulterated with cheaper starches. 

PMID- 23871066
TI  - Thermodynamics of the enantiomers of amino acid and monosaccharide binding to
      fullerenol used as an artificial sweet taste receptor model.
AB  - Fullerenol was used as sweet taste receptor model to investigate the binding
      affinities of structurally related pairs of enantiomers by isothermal titration
      calorimetry (ITC). It reveals that amino acid binding with fullerenol are
      enthalpy-cost and entropically-driven processes, whereas enthalpy contributes to
      monosaccharide binding to fullerenol. Spontaneous binding of amino acids was
      found through two sequential steps in which the sweeter enantiomer displays
      larger binding constants. Association of the d-form of fructose and l-form
      galactose with fullerenol suggested that, the higher the perceived sweetness
      intensity of the enantiomer, the larger was the binding constant with respect to
      their antipodes. Further investigation by molecular dynamic simulation showed
      that the binding energy and the perceived sweetness intensity were well
      correlated. The preliminary results of this biomimetic research cover the lack of
      information about the thermodynamic basis of sweet sensation and the underlying
      principles of sweetness differences between the enantiomers of amino acids and
      monosaccharides. 

PMID- 23871067
TI  - Removal of aflatoxin B(1) in edible plant oils by oscillating treatment with
      alkaline electrolysed water.
AB  - Alkaline electrolysed water (AlEW) with different pHs was produced by an
      electrolysed water generator through adjusting the electric current and voltage.
      The produced AlEW had a pH above 10, and a low oxidation-reduction potential
      (ORP) of less than -560 mV. In the current study, the effectiveness of AlEW on
      decontamination of aflatoxin B1 (AFB1) in various edible plant oils was
      investigated. The character of AlEW, oil type and the volume of AlEW were major
      factors which could influence the AFB1 elimination effectiveness. AlEW with pH
      12.2 had the greater potential to remove AFB1. When 10 ml AlEW with pH 12.2 were
      added to 5 g peanut oil or olive oil (fortified level at 40 MUg kg(-1)), followed
      by oscillation for 5 min at 20  degrees C, the removal rate of AFB1 could reach
      nearly 100%. The volume of AlEW needed to completely remove the AFB1 varied with
      the pH of AlEW and with the oil type. The degradation products of AFB1 were also
      investigated.

PMID- 23871068
TI  - Red wines attenuate TNFalpha production in human histiocytic lymphoma cell line:
      an NMR spectroscopy and chemometrics based study.
AB  - Nuclear magnetic resonance (NMR) spectroscopy and multivariate data analyses
      methods are applied to the metabolic profiling of different red wines from
      Portugal. The water, methanol-water (1:1), and methanol fractions from solid
      phase extraction (SPE) with C18 resin were subjected to in vitro TNFalpha
      activity assay. Principal component analysis allowed the clear separation among
      the different SPE fractions according to the activity. Various supervised data
      reduction algorithms were tested and compared to highlight the TNFalpha
      inhibition by SPE fractions of wines. Partial least squares-discriminant analysis
      and orthogonal bidirectional PLS-DA were found most effective in discriminating
      the samples with different activities. By calculating variable importance in the
      projection, the active ingredients in the high activity samples have been
      identified as caftaric acid, quercetin, and catechin. Among the different
      vintages, samples from 2010 vintage were found with maximum anti-TNFalpha
      activity. The effectiveness of NMR spectroscopy in combination with chemometrics
      to identify the possible bioactivity in the several crude extracts is
      highlighted. 

PMID- 23871069
TI  - Impact of high-intensity pulsed electric fields on carotenoids profile of tomato
      juice made of moderate-intensity pulsed electric field-treated tomatoes.
AB  - The effect of pulsed electric fields (PEF) on the carotenoid content of tomato
      juices was studied. First, moderate-intensity PEF (MIPEF) was applied to raw
      tomatoes. Afterwards, MIPEF-treated and untreated tomatoes were immediately
      refrigerated at 4  degrees C for 24 h and then, they were separately ground to
      produce tomato juices. Juices were treated by heat treatments or by high
      intensity PEF (HIPEF) and stored under refrigeration for 56 days. MIPEF treatment
      of tomatoes increased the content of carotenoid compounds in tomato juices. An
      enhancement of 63-65% in 15-cis-lycopene was observed in juices prepared with
      MIPEF-treated tomatoes. A slight increase in cis-lycopene isomers was observed
      over time, whereas other carotenoids slightly decreased. However, HIPEF treated
      tomato juices maintained higher carotenoid content (10-20%) through the storage
      time than thermally and untreated juices. The combination of MIPEF and HIPEF
      treatments could be used not only to produce tomato juices with high carotenoid
      content but also, to maintain higher the carotenoid content during storage time.

PMID- 23871070
TI  - The decay of ascorbic acid in a model wine system at low oxygen concentration.
AB  - The present study investigated the impact of temperature on the degradation of
      ascorbic acid in low oxygen conditions in a model white wine. The concentrations
      of ascorbic acid, furfural, sulfur dioxide and phenolic-type products were
      monitored in a model white wine stored under non-oxidative conditions at 45.0,
      36.5 and 24.0  degrees C for up to 693 days. The concentrations of both ascorbic
      acid and sulfur dioxide decreased over the analysis period while furfural and
      other colourless phenolic products increased in concentration, despite the
      presence of residual sulfur dioxide. The decay of ascorbic acid in the low oxygen
      conditions followed first-order kinetics and the rate constants were determined
      to be (3.5+/-0.2)*10(-8), (1.02+/-0.07)*10(-8), and (0.184+/-0.009)*10(-8) s(-1)
      for 45.0, 36.5 and 24.0  degrees C (n=5, standard error), respectively, and the
      activation energy was 110+/-3 kJ/mol (n=3, standard error). Importantly, these
      data allow more accurate prediction of the temperature-induced loss of ascorbic
      acid in low oxygen conditions during transport or storage of wine.

PMID- 23871071
TI  - Effect of Zingiber officinale essential oil on Fusarium verticillioides and
      fumonisin production.
AB  - The antifungal activity of ginger essential oil (GEO; Zingiber officinale Roscoe)
      was evaluated against Fusarium verticillioides (Saccardo) Nirenberg. The minimum
      inhibitory concentration (MIC) of GEO was determined by micro-broth dilution. The
      effects of GEO on fumonisin and ergosterol production were evaluated at
      concentrations of 500-5000 MUg/mL in liquid medium with a 5mm diameter mycelial
      disc of F. verticillioides. Gas chromatography-mass spectrometry showed that the
      predominant components of GEO were alpha-zingiberene (23.9%) and citral (21.7%).
      GEO exhibited inhibitory activity, with a MIC of 2500 MUg/mL, and 4000 and 5000
      MUg/mL reduced ergosterol biosynthesis by 57% and 100%, respectively. The
      inhibitory effect on fumonisin B1 (FB1) and fumonisin B2 (FB2) production was
      significant at GEO concentrations of 4000 and 2000 MUg/mL, respectively. Thus,
      the inhibition of fungal biomass and fumonisin production was dependent on the
      concentration of GEO. These results suggest that GEO was able to control the
      growth of F. verticillioides and subsequent fumonisin production.

PMID- 23871072
TI  - Organoleptic and chemical quality of farmed meagre (Argyrosomus regius) as
      affected by size.
AB  - Two fish groups differing in size (average weighing 830+/-220 and 1600+/-350 g,
      respectively) were evaluated for their sensory, somatometric and chemical quality
      characteristics. No differences were found in the yields and fillet proximate
      composition of the two groups. Although taste panels indicated high acceptability
      for both groups, the large fish received significantly better hedonic rates for
      their overall acceptance. Differences were also observed in the fatty acid
      profiles of the two groups with the large fish having significantly higher 18:2n
      6 and total n-6 contents. Their volatile compounds also differed, with small fish
      containing higher total amount, as well as more total aldehydes, furans and
      pyrazines. All these findings indicate size-dependent quality alterations, but
      also sufficient quality for small fish to be commercialised.

PMID- 23871073
TI  - Use of allyl isothiocyanate and carbon nanotubes in an antimicrobial film to
      package shredded, cooked chicken meat.
AB  - We developed antimicrobial packaging incorporated with allyl isothiocyanate (AIT)
      and carbon nanotube (CNT), and this packaging was used for shredded cooked
      chicken meat inoculated with Salmonella Choleraesuis. The following parameters
      were analysed during the 40 days of storage: microbial counts, colour
      characteristics and changes in the oxidation of the meat as well as changes in
      the mechanical properties of the film, the structure of the antimicrobial film
      and the diffusion of the antimicrobial agent into the food. The incorporation of
      AIT into the films increased the elongation at the break (E) value of the films
      and decreased the tensile strength (TS) value of the films. The CNT was important
      to retain the AIT which is a volatile substance in the film. The diffusion of the
      AIT from the film into the chicken reduced the microbial contamination,
      controlled oxidation and reduced the colour changes. Thus, these packages were
      effective for the 40 days of storage.

PMID- 23871074
TI  - Citron and lemon under the lens of HR-MAS NMR spectroscopy.
AB  - High Resolution Magic Angle Spinning (HR-MAS) is an NMR technique that can be
      applied to semi-solid samples. Flavedo, albedo, pulp, seeds, and oil gland
      content of lemon and citron were studied through HR-MAS NMR spectroscopy, which
      was used directly on intact tissue specimens without any physicochemical
      manipulation. HR-MAS NMR proved to be a very suitable technique for detecting
      terpenes, sugars, organic acids, aminoacids and osmolites. It is valuable in
      observing changes in sugars, principal organic acids (mainly citric and malic)
      and ethanol contents of pulp specimens and this strongly point to its use to
      follow fruit ripening, or commercial assessment of fruit maturity. HR-MAS NMR was
      also used to derive the molar percentage of fatty acid components of lipids in
      seeds, which can change depending on the Citrus species and varieties. Finally,
      this technique was employed to elucidate the metabolic profile of mold flavedo. 

PMID- 23871075
TI  - Metabolic alterations of lutein, beta-carotene and chlorophyll a during
      germination of two soybean sprout varieties.
AB  - The metabolic changes of lutein, beta-carotene and chlorophyll a during
      germination of the soybean (Glycine max (L.) Merr.) sprout varieties,
      'Pungsannamulkong' and 'Bosug', have been studied. Seeds were germinated at 20 
      degrees C with 80% humidity in the darkness and sampled at 2 day intervals for 10
      days. Partial least squares (PLS) scores plot showed that the responses of three
      metabolites during germination were linearly linked with each other except for
      day 2 in both varieties. PLS loading plots indicated that lutein content in whole
      sprout and cotyledon was closely associated with germination in
      'Pungsannamulkong' while the chlorophyll a content in whole sprouts was highly
      linked with germination in 'Bosug'. Heatmap analyses revealed that lutein and
      beta-carotene levels, but not those of chlorophyll a, accumulated in whole
      soybean sprouts and cotyledon. While hypocotyls did not accumulate lipophilic
      pigments during germination, the accumulation of lutein and beta-carotene in the
      cotyledons was greater in 'Pungsannamulkong' than in 'Bosug' sprouts. In
      addition, the contents of lutein, beta-carotene and chlorophyll a increased from
      those in the seeds. Overall, the metabolic changes of lutein, beta-carotene and
      chlorophyll a during germination are affected not only by variety but also by
      organ type.

PMID- 23871077
TI  - Evaluation of gallic acid loaded zein sub-micron electrospun fibre mats as novel
      active packaging materials.
AB  - The applicability of gallic acid loaded zein (Ze-GA) electrospun fibre mats
      towards potential active food packaging material was evaluated. The surface
      chemistry of the electrospun fibre mats was determined using X-ray photon
      spectroscopy (XPS). The electrospun fibre mats showed low water activity and
      whitish colour. Thermogravimetric analysis (TGA) and Attenuated Total Reflectance
      Fourier Transform Infrared (ATR-FTIR) spectroscopy revealed the stability of the
      fibre mats over time. The Ze-GA fibre mats displayed similar rapid release
      profiles, with Ze-GA 20% exhibiting the fastest release rate in water as compared
      to the others. Gallic acid diffuses from the electrospun fibres in a Fickian
      diffusion manner and the data obtained exhibited a better fit to Higuchi model.
      L929 fibroblast cells were cultured on the electrospun fibres to demonstrate the
      absence of cytotoxicity. Overall, the Ze-GA fibre mats demonstrated antibacterial
      activity and properties consistent with those considered desirable for active
      packaging material in the food industry. 

PMID- 23871076
TI  - Anti-neuroinflammatory capacity of fresh ginger is attributed mainly to 10
      gingerol.
AB  - Despite the anti-neuroinflammatory capacity of ginger, the corresponding active
      constituents are unclear. This study analyzed the composition of fresh ginger
      ethanolic extract by using LC-MS. Inhibitory activities of fresh ginger extract
      and seven gingerol-related compounds on the neuro-inflammation were also
      evaluated by using a lipopolysaccharide (LPS)-activated BV2 microglia culture
      model. Except for zingerone and 6-gingerol, other gingerols and shogaols at a
      concentration of 20 MUM inhibited the production of nitric oxide, IL-1beta, IL-6
      and TNF-alpha as well as their mRNA levels in LPS-activated BV2 microglia.
      Blocking NF-kappaB activation was the underlying mechanism responsible for
      inhibiting the proinflammatory gene expression. Increasing the alkyl chain length
      enhanced the anti-neuroinflammatory capacity of gingerols yet, conversely,
      attenuated those of shogaols. 6-Gingerol was the most abundant compound in the
      fresh ginger extract, followed by 10-gingerol. Furthermore, fresh ginger extract
      exhibited a significant anti-neuroinflammatory capacity, which was largely owing
      to 10-gingerol, but not 6-gingerol.

PMID- 23871078
TI  - Effects of ultrasound treatments on quality of grapefruit juice.
AB  - Sonication is recognised as a potential technique for improvement in the quality
      of fruit juices. This study was initiated with the objective of evaluating the
      effect of sonication treatments on some important quality parameters of
      grapefruit juice such as physico-chemical (pH, acidity and  degrees Brix), Hunter
      colour values (L(*), a(*) and b(*)), cloud value, electrical conductivity, total
      antioxidant capacity, DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical
      scavenging activity, ascorbic acid, total phenolics, flavonoids and flavonols.
      Sonication of grapefruit juice was done in a bath type sonicator at a frequency
      of 28 kHz by maintaining a constant temperature of 20  degrees C. Results showed
      that there was significant improvement in the cloud value, total antioxidant
      capacity, DPPH free radical scavenging activity, ascorbic acid, total phenolics,
      flavonoids and flavonols in all the juice samples sonicated for 30, 60 and 90 min
      but no changes occurred in the pH, acidity and  degrees Brix value as compared to
      control. Some differences in all the colour values were also observed but overall
      quality of grapefruit juice was improved, suggesting that sonication technique
      may successfully be implemented an industrial scale for the processing of
      grapefruit juice.

PMID- 23871079
TI  - Effect of pH(24h), curing salts and muscle types on the oxidative stability, free
      amino acids profile and vitamin B2, B3 and B6 content of dry-cured ham.
AB  - The effects of a curing salt composition (with and without nitrifying salts), and
      the pH at 24h postmortem (pH24>6.0, 5.5<pH24<6.0 and pH24<5.5) were evaluated in
      the Semimembranosus (SM) and Biceps femoris (BF) muscles of pork legs for
      compositional and nutritional attributes at the end of dry-cured ham ageing. The
      muscles free amino acid profile (FAA) was not influenced by nitrifying salts. The
      pH24 was the factor which had the greatest consequences on the dry-cured ham
      characteristics analysed. The increase in nicotinamide and decrease in pyridoxine
      by curing salts and the decrease in both vitamins by pH24, had no major effect on
      the nutritional value of the dry-cured ham because the remaining amounts were
      within the intervals found in the nutritional data base for dry-cured ham. The
      results obtained suggested a cooperative action of vitamins B3 and B6 and the
      antioxidant enzyme system against oxidation. Thiobarbituric acid reactive
      substances (TBARS) were reduced by the addition of curing salts but were low in
      all cases, suggesting high antioxidant stability in dry-cured ham which was
      corroborated by the low volatile aldehyde contents. 

PMID- 23871080
TI  - In vivo digestion of bovine milk fat globules: effect of processing and
      interfacial structural changes. II. Upper digestive tract digestion.
AB  - The aim of this research was to study the effect of milk processing on the in
      vivo upper digestive tract digestion of milk fat globules. Fasted rats were
      serially gavaged over a 5h period with cream from raw, pasteurised, or
      pasteurised and homogenised milk. Only a few intact dietary proteins and peptides
      were present in the small intestinal digesta. Significantly (P<0.05) more longer
      chain (C>=10) fatty acids were present in the digesta of rats gavaged with raw
      (448 mg g(-1) digesta dry matter (DDM)) and homogenised creams (528 mg g(-1)
      DDM), as compared to pasteurised and homogenised cream (249 mg g(-1) DDM).
      Microscopy techniques were used to investigate the structural changes during
      digestion. Liquid-crystalline lamellar phases surrounding the fat globules, fatty
      acid soap crystals and lipid-mucin interactions were evident in all small
      intestinal digesta. Overall, the pasteurised and homogenised cream appeared to be
      digested to a greater extent.

PMID- 23871081
TI  - Effect of protein oxidation on the in vitro digestibility of soy protein isolate.
AB  - Soy protein isolate (SPI) was modified by 2,2'-azobis (2-amidinopropane)
      dihydrochloride (AAPH) oxidation pretreatment, and the in vitro digestibility of
      oxidised SPI was investigated. Results indicated that oxidation induced amino
      acid modification. The amount of most amino acids decreased, accompanied by
      decreasing digestive proteolysis susceptibility. Peptide size distribution
      implied that oxidation generated protein aggregates that could not be degraded by
      pepsin, but could be digested by pancreatin. Oxidation induced a maximum of 16.6%
      and 14.6% loss, respectively, for free essential and free total amino acid in the
      digests of oxidised SPI. Antioxidant activities evaluation of oxygen radical
      absorbance capacity (ORAC) value and DPPH scavenging activity showed that
      oxidation deteriorated the antioxidant activities of the digests from oxidised
      SPI. 

PMID- 23871082
TI  - Evolution of colour and phenolic compounds during Garnacha Tintorera grape
      raisining.
AB  - The off-vine drying is one of the most important steps in the production of a
      high quality naturally sweet wine. However, only few studies have analyzed the
      changes in colour and phenolic compounds of the grapes throughout the process. In
      this work, UV/Vis spectrophotometry and HPLC/DAD-ESI/MS were applied to
      determine, respectively, the evolution of colour and phenolic compounds in the
      red grapes of Garnacha Tintorera during the raisining process. The total water
      loss in 83 days was about 62% and the sugar concentration rose from 225 to 464 g
      L(-1). Browning and low-medium molecular weight compounds increase during the
      dehydration process. In CIELab coordinates, raisining decreases a(*) (red/green)
      and lightness and increases b(*) (yellow/blue), colour saturation and hue angle.
      In general, most of the phenolic compounds determined (anthocyanins, flavonols,
      esters of hydroxycinnamic acids, flavan-3-ol monomers and proanthocyanidins)
      increase but to a lesser extent than expected because of the water loss of the
      grapes during drying. The lower increase was observed for esters of
      hydroxicinnamic acids suggesting these compounds could undergo strong enzymatic
      degradation. Despite this, both the terminal and the extension subunit
      compositions show little changes, while the mean degree of polymerization of
      proanthocyanidins decreases as raisining progresses.

PMID- 23871083
TI  - New vinegar produced by tomato suppresses adipocyte differentiation and fat
      accumulation in 3T3-L1 cells and obese rat model.
AB  - There is an increasing surplus of tomatoes that are abandoned due to their
      failure to meet customer standards. Therefore, to allow both value additions and
      the effective reuse of surplus tomatoes, we developed tomato vinegar (TV)
      containing phytochemicals and evaluated its anti-obesity effects in vitro and in
      vivo. TV inhibited adipocyte differentiation of 3T3-L1 preadipocyte and lipid
      accumulation during differentiation. TV supplementation in rats fed a high-fat
      diet (HFD) markedly decreased visceral fat weights without changing the food and
      calories intakes. TV significantly decreased hepatic triglyceride and cholesterol
      levels compared to the HFD group. Furthermore, TV lowered plasma LDL-cholesterol
      level and antherogenic index compared to the HFD group, whereas elevated HDL
      cholesterol to total cholesterol ratio. These results show that TV prevented
      obesity by suppressing visceral fat and lipid accumulation in adipocyte and obese
      rats, and suggest that TV can be used as an anti-obesity therapeutic agent or
      functional food. 

PMID- 23871084
TI  - Glycation promoted by dynamic high pressure microfluidisation pretreatment
      revealed by high resolution mass spectrometry.
AB  - The effect of dynamic high pressure microfluidisation (DHPM) pretreatment on the
      glycation of bovine serum albumin (BSA) was investigated. A detailed glycation
      map was obtained from high resolution mass spectrometry. Without DHPM
      pretreatment, only 7 glycation sites were identified, whereas the numbers were
      increased to 10, 11 and 11 when BSA-glucose was pretreated with DHPM at 50, 100
      and 200 MPa, respectively, suggesting that DHPM pretreatment can significantly
      promote the Maillard reaction. Average degree of substitution per peptide
      molecule BSA (DSP) was used to further evaluate the glycation level under various
      DHPM conditions. All the DHPM pretreated samples exhibited elevated glycation
      level compared to the un-pretreated sample. With 100 MPa DHPM pretreatment, the
      protein showed the most significantly enhanced glycation extent. In addition, our
      results suggest that Maillard-type glycation followed by mass spectrometry
      analysis can be used to study the conformational changes when proteins are
      disturbed by external forces.

PMID- 23871085
TI  - The identification of degradation products and degradation pathway of malvidin-3
      glucoside and malvidin-3,5-diglucoside under microwave treatment.
AB  - Understanding the degradation of anthocyanins (Acys) during microwave treatment
      is required for the application of this novel technology to fruit and vegetable
      processing. The pH 3.5 buffer solutions containing 50mg/l malvidin-3-glucoside
      (Mv-3-glu) and malvidin-3,5-diglucoside (Mv-3,5-diglu), respectively, were
      treated with microwaves at 700 W. In comparison, the samples were heated at 98+/
      2  degrees C in a water bath. In total, nine degradation products were detected
      (using LC-UV/Vis-MS/MS) for each Acys after microwave treatment. Anthocyanone A,
      hydroxycoumarins and dihydroxy phenylacetaldehyde were characterised as the main
      degradation products of both Acys under microwave conditions, which were not
      detected in the thermal treatment. In addition, syringic acid, 2,4,6
      trihydroxybenzaldehyde, coumarin glucosides and 2,6-dimethoxyphenol were found
      simultaneously under the microwave and thermal treatments. During the microwave
      treatment, hydrogen peroxide was formed and resulted in the Baeyer-Villiger-type
      oxidation of the Acys, which was the main degradation pathway. At the same time,
      the conventional thermal degradation pathway of Acys also occurred.

PMID- 23871086
TI  - An innovative grape juice enriched in polyphenols by microwave-assisted
      extraction.
AB  - The grape juice by-product obtained from grape traditional press was extracted by
      Microwave Hydrodiffusion and Gravity (MHG); a green extraction technique
      preliminarily optimized at 1 W/g. The MHG extract (MHGE) was analyzed by HPLC for
      identification and quantification of anthocyanins and other phenolic compounds.
      Then, MHGE was added to the natural juice (NJ) to produce an innovative grape
      juice (IJ). These three juices were evaluated for their total polyphenol content
      (TPC), total anthocyanin content (TAC) in addition to their sensorial
      characteristics. MHGE showed the highest values of TPC (21.41+/-0.04 mg GAE/g
      DW), TAC (4.49+/-0.01 MUg MVGE/g DW). Moreover, IJ (grape juice enriched with
      MHGE) was richer in TPC (6.70+/-0.0 1mg GAE/g DW) and TAC (3.96+/-0.01 MUg MVGE/g
      DW) than NJ (2.90+/-0.02 mg GAE/g DW and 3.63+/-0.06 MUg MVGE/g DW,
      respectively).

PMID- 23871087
TI  - In vivo digestion of bovine milk fat globules: effect of processing and
      interfacial structural changes. I. Gastric digestion.
AB  - The aim was to study the in vivo gastric digestion of fat globules in bovine
      cream from raw, pasteurised or pasteurised and homogenised milk. Fasted rats were
      gavaged once and chyme samples were collected after 30, 120 and 180 min post
      gavage. Proteins from raw (RC) and pasteurised (PC) creams appeared to be
      digested faster and to a greater extent. Free fatty acids (FAs) increased
      throughout the 3h postprandial period. Short and medium chain FAs were released
      more rapidly than long chain FAs which were hydrolysed to a greater degree from
      PC. The size of the fat globules of all creams increased in the stomach. Protein
      aggregates were observed in pasteurised and homogenised cream chyme. Protrusions,
      probably caused by the accumulation of insoluble lipolytic products, appeared at
      the surface of the globules in RC and PC chyme. Overall, PC proteins and lipids
      appeared to be digested to a greater extent.

PMID- 23871088
TI  - The relationship between the structure and biological actions of green tea
      catechins.
AB  - Catechins and their gallate esters are a class of polyphenolic compounds. The
      catechin subclass known as flavan-3-ols have recently attracted much attention
      with regards to their beneficial effect on human health. Their biological actions
      are dependent on the structure of the compounds and vary according to cell type.
      They are best known as powerful antioxidants; however depending on the doses they
      also exhibit prooxidant effects. The anti- or prooxidant effects of green tea
      catechins have been implicated in the modulation of several cellular functions
      often associated with strong chemoprotective properties. This review summarises
      the benefit catechins to human health, the main molecular pathways modulated by
      catechins. The relationship between the structure and activity of the catechins
      needs to be studied further. In the future, the structure of catechins could be
      modified so as to synthesise novel compounds with more specific beneficial
      properties and higher bioavailability. 

PMID- 23871089
TI  - Oversight of constipation in inpatients with schizophrenia: a cross-sectional
      study.
AB  - OBJECTIVE: Constipation is often overlooked in patients with schizophrenia. We
      examined their awareness of constipation and whether they reported it to their
      psychiatrists. METHOD: Five hundred three inpatients with schizophrenia
      (International Classification of Diseases, 10th Revision) were interviewed about
      their recent bowel movements and evaluated for the diagnostic criteria for
      functional constipation. If constipation was present, patients were asked if they
      were aware of it and had reported it to their psychiatrists in charge.
      Additionally, their global psychopathology and functioning were assessed using
      the Clinical Global Impression-Schizophrenia (CGI-SCH) and the Global Assessment
      of Functioning (GAF), respectively. RESULTS: The criteria for constipation were
      met by 184 patients (36.6%); of these patients, only 56.0% (103/184) were aware
      of it. Moreover, only 34 of the constipated patients (18.5%) reported its
      presence to their psychiatrists. No significant differences were found in the CGI
      SCH overall severity or subscale scores or in the GAF scores between those
      patients who reported and those who failed to report constipation. CONCLUSIONS:
      The present study demonstrated that constipation was neither recognized nor
      reported to psychiatrists by a significant percentage of the patients. These
      findings underscore the importance of greater vigilance and active evaluation of
      constipation in patients with schizophrenia for appropriate clinical management.

PMID- 23871090
TI  - Achalasia.
AB  - Achalasia is a rare motility disorder of the oesophagus characterised by loss of
      enteric neurons leading to absence of peristalsis and impaired relaxation of the
      lower oesophageal sphincter. Although its cause remains largely unknown,
      ganglionitis resulting from an aberrant immune response triggered by a viral
      infection has been proposed to underlie the loss of oesophageal neurons,
      particularly in genetically susceptible individuals. The subsequent stasis of
      ingested food not only leads to symptoms of dysphagia, regurgitation, chest pain,
      and weight loss, but also results in an increased risk of oesophageal carcinoma.
      At present, pneumatic dilatation and Heller myotomy combined with an anti-reflux
      procedure are the treatments of choice and have comparable success rates. Per
      oral endoscopic myotomy has recently been introduced as a new minimally invasive
      treatment for achalasia, but there have not yet been any randomised clinical
      trials comparing this option with pneumatic dilatation and Heller myotomy. 

PMID- 23871091
TI  - Thermal effects on human performance in office environment measured by
      integrating task speed and accuracy.
AB  - We have proposed a method in which the speed and accuracy can be integrated into
      one metric of human performance. This was achieved by designing a performance
      task in which the subjects receive feedback on their performance by informing
      them whether they have committed errors, and if did, they can only proceed when
      the errors are corrected. Traditionally, the tasks are presented without giving
      this feedback and thus the speed and accuracy are treated separately. The method
      was examined in a subjective experiment with thermal environment as the
      prototypical example. During exposure in an office, 12 subjects performed tasks
      under two thermal conditions (neutral & warm) repeatedly. The tasks were
      presented with and without feedback on errors committed, as outlined above. The
      results indicate that there was a greater decrease in task performance due to
      thermal discomfort when feedback was given, compared to the performance of tasks
      presented without feedback. 

PMID- 23871092
TI  - Long-term consequences of subarachnoid hemorrhage: examining working memory.
AB  - Working memory impairments are prevalent among survivors of aneurysmal
      subarachnoid hemorrhage (SAH), but few studies have examined specifically these
      impairments. Such an examination is important because working memory processes
      are vital for daily cognitive functioning. In the current study, patients with
      SAH and healthy control participants were administered the word-span and alpha
      span test - experimental tests of working memory. In the word-span test,
      participants recalled increasingly longer word-lists, requiring the maintenance
      of information in mind. In the alpha-span test, participants recalled the word
      lists in alphabetical order, requiring both the maintenance and manipulation of
      information. Patients with SAH were no different from healthy controls on a
      battery of standard neuropsychological measures or on the word-span test. They
      were, however, significantly impaired on the alpha-span test, suggesting a
      deficit in the manipulation components of working memory. That is, impairment
      resulting from SAH is present when a working memory task requires additional
      executive processing demands. This deficit in patients with SAH does not appear
      to be influenced by aneurysm location, suggesting that some of the effects of SAH
      on cognition are from diffuse rather than focal pathology; however, a larger
      sample size is needed to reinforce this claim. 

PMID- 23871093
TI  - The efficacy and safety of aspirin plus dipyridamole versus aspirin in secondary
      prevention following TIA or stroke: a meta-analysis of randomized controlled
      trials.
AB  - OBJECTIVE: Stroke is becoming a common disease worldwide, and has an increased
      rate of recurrence yearly after a transient ischemic attack (TIA) or stroke.
      Aspirin, dipyridamole, clopidogrel and aspirin plus dipyridamole combination
      therapy have been recommended for the secondary prevention of stroke in
      Americans. DESIGN: We performed meta-analyses to assess the effectiveness and
      safety of combination therapy with aspirin and dipyridamole (A+D) versus aspirin
      (A) alone in secondary prevention after transient ischemic attack (TIA) or stroke
      of presumed arterial origin within one week and six months. DATA SOURCES:
      Medline, Embase, and the Cochrane Library. SELECTION OF STUDIES: Eligible studies
      were completed randomized controlled trials investigating the effect of aspirin
      plus dipyridamole versus aspirin in patients with previous TIA or stroke.
      RESULTS: Five trials involving the use of aspirin and dipyridamole were included,
      4318 allocated to A+D and 4304 to A alone. Meta-analysis of trials showed a
      significant protective effect of reducing or preventing recurrence of stroke
      (P=0.01), and ischemic event (P=0.003). The statistics showed no significant
      difference in vascular event, death from all cause and myocardial infarction
      (P>0.05). There were similarities with all bleeding events, major bleeding and
      intracranial hemorrhage was significant (P>0.05) between two groups. CONCLUSIONS:
      Aspirin plus dipyridamole combination therapy was beneficial in reducing the
      recurrence of stroke, and did not increase the bleeding event. Hence, aspirin
      plus dipyridamole combination therapy is effective and safe for the secondary
      prevention of stroke.

PMID- 23871094
TI  - High-definition endoscopy with i-Scan for evaluation of small colon polyps: the
      HiSCOPE study.
AB  - BACKGROUND: Traditional white-light endoscopy cannot reliably distinguish between
      small (<10 mm) adenomatous and hyperplastic colon polyps. High-definition white
      light (HDWL) endoscopy and i-Scan may improve in vivo characterization of small
      colon polyps. OBJECTIVE: To compare HDWL endoscopy and HDWL plus i-Scan for the
      assessment of small colon polyps and to measure performance against the American
      Society for Gastrointestinal Endoscopy (ASGE) thresholds for assessment of
      diminutive colon polyps. DESIGN: Prospective cohort study. SETTING: Single
      academic hospital. PATIENTS: Patients undergoing bowel cancer screening
      colonoscopy. INTERVENTION: In vivo assessment of all polyps <10 mm by using HDWL
      and i-Scan image enhancement. MAIN OUTCOME MEASUREMENTS: The primary outcome
      measure was overall diagnostic accuracy of in vivo assessment of colon polyps <10
      mm. Secondary outcome measures were sensitivity and specificity for adenomatous
      histology, negative predictive value for adenomatous histology of diminutive
      rectosigmoid polyps, and accuracy of prediction of polyp surveillance intervals.
      RESULTS: A total of 209 polyps in 84 patients were included. There were no
      significant differences between HDWL endoscopy and i-Scan in characterization of
      polyps <10 mm (accuracy 93.3% vs 94.7%; P = 1.00; sensitivity 95.5% vs 97.0%; P =
      .50; specificity 89.3% vs 90.7%; P = 1.00). The negative predictive value for
      adenomatous histology of diminutive rectosigmoid polyps was 100% with both HDWL
      endoscopy and i-Scan. U.K. and U.S. polyp surveillance intervals were predicted
      with 95.2% accuracy with HDWL endoscopy and 97.2% accuracy with i-Scan.
      LIMITATIONS: Single-center study. CONCLUSION: HDWL endoscopy may be as accurate
      as HDWL with i-Scan image enhancement for the in vivo characterization of small
      colon polyps. Both modalities fulfil the ASGE performance thresholds for the
      assessment of diminutive colon polyps. ( CLINICAL TRIAL REGISTRATION NUMBER:
      NCT01761279.).

PMID- 23871095
TI  - Utility of an endoscopic suturing system for prevention of covered luminal stent
      migration in the upper GI tract.

PMID- 23871096
TI  - [Changes in driving skills in patients who start treatment with efavirenz].

PMID- 23871097
TI  - [Ultrasound-guided peripheral venous cannulation in a surgical patient].

PMID- 23871098
TI  - [Perioperative management of type 2B Von Willebrand's disease in a patient
      undergoing urgent abdominal surgery].

PMID- 23871099
TI  - Adjuvant chemotherapy in colon cancer: can we improve quality of care?

PMID- 23871100
TI  - Scoring functions for protein-protein interactions.
AB  - The computational evaluation of protein-protein interactions will play an
      important role in organising the wealth of data being generated by high
      throughput initiatives. Here we discuss future applications, report recent
      developments and identify areas requiring further investigation. Many functions
      have been developed to quantify the structural and energetic properties of
      interacting proteins, finding use in interrelated challenges revolving around the
      relationship between sequence, structure and binding free energy. These include
      loop modelling, side-chain refinement, docking, multimer assembly, affinity
      prediction, affinity change upon mutation, hotspots location and interface
      design. Information derived from models optimised for one of these challenges can
      be used to benefit the others, and can be unified within the theoretical
      frameworks of multi-task learning and Pareto-optimal multi-objective learning. 

PMID- 23871101
TI  - New crystal structures of PII-type ATPases: excitement continues.
AB  - P-type ATPases are ATP-powered ion pumps, classified into five subfamilies (PI
      PV). Of these, PII-type ATPases, including Ca2+-ATPase, Na+,K+-ATPase and gastric
      H+,K+-ATPase, among others, have been the most intensively studied. Best
      understood structurally and biochemically is Ca2+-ATPase from sarcoplasmic
      reticulum of fast twitch skeletal muscle (sarco(endo)plasmic reticulum Ca2+
      ATPase 1a, SERCA1a). Since publication of the first crystal structure in 2000, it
      has continuously been a source of excitement, as crystal structures for new
      reaction intermediates always show large structural changes. Crystal structures
      now exist for most of the reaction intermediates, almost covering the entire
      reaction cycle. This year the crystal structure of a missing link, the E1.Mg2+
      state, finally appeared, bringing another surprise: bound sarcolipin (SLN). The
      current status of two other important PII-type ATPases, Na+,K+-ATPase and H+,K+
      ATPase, is also briefly described.

PMID- 23871103
TI  - Seizure outcome of infantile spasms with focal cortical dysplasia.
AB  - PURPOSE: This study sought to evaluate the seizure outcome of infantile spasms
      (IS) with focal cortical dysplasia (FCD). METHODS: We retrospectively reviewed
      infantile spasms patients with FCD from 2004 to 2010. We investigated seizure
      outcome from antiepileptic drug (AED), ketogenic diet (KD), resective surgery,
      and analyzed the results according to individual imaging studies. RESULTS: Among
      404 patients of IS, FCD was confirmed in 51 patients. In retrospective review of
      brain MRI, only 21 patients (41.2%) were suspected of FCD before 1year of age,
      but 45 patients (88.2%) became confirmed to FCD by MRI after the age of 1year.
      Once the spasms were not controlled by 1 or 2 AEDs, the chance of becoming
      seizure free with additional third or more drugs was very low (2.3%). The seizure
      free rate was 33.3% (7/21) in patients treated with ketogenic diet, and 73.3%
      (22/30) in surgical patients, who were both intractable to AEDs. There were no
      significant differences in seizure free rate in both ketogenic diet and surgical
      patients, between MRI negative and positive patients prior to 1year of age.
      CONCLUSIONS: KD and surgery should be considered in medically refractory IS with
      FCD.

PMID- 23871104
TI  - A comparison of fruit and vegetable intake estimates from three survey question
      sets to estimates from 24-hour dietary recall interviews.
AB  - BACKGROUND: Fruit and vegetable (F/V) intake surveillance can provide information
      critical to the design and evaluation of interventions and the assessment of
      progress toward national intake objectives. The CDC's Youth Risk Behavior
      Surveillance System (YRBSS) assesses F/V intake among high school students using
      six questions about the frequency of intake in times per day. It is not known
      whether F/V intake frequency in times per day can be used as a proxy for intake
      in servings per day. OBJECTIVE: To compare F/V intake estimates based on
      responses to three sets of survey questions, including the standard set of six
      YRBSS questions, with criterion F/V intake in servings per day based on data from
      24-hour dietary recall interviews. PARTICIPANTS/SETTING: Study participants were
      610 high school students who completed an in-class questionnaire and three
      telephone-administered 24-hour dietary recall interviews. The questionnaire asked
      students how many times they consumed 100% fruit juice and ate fruit, carrots,
      potatoes, green salad, and other vegetables during the "past 7 days" (set 1), the
      number of times they did so "yesterday" (set 2), and the number of cup
      equivalents of fruits and vegetables they consumed per day (set 3). MAIN OUTCOME
      MEASURE: Mean estimated F/V intake either as "times/day" or "servings/day" and
      the percentage of students whose estimated F/V intake was >=1, >=2, and >=3
      times/day or servings/day. STATISTICAL ANALYSES PERFORMED: t tests and corrected
      Pearson correlations were used to compare F/V intake estimates based on survey
      question responses with estimates based on responses to the 24-hour dietary
      recall interviews. RESULTS: Mean F/V intake estimates (in times/day or
      servings/day) based on responses to all sets of survey questions were
      significantly more than servings/day estimates based on responses to the 24-hour
      dietary recall interviews, and the percentages of students meeting each intake
      cutpoint were also more. Of the three sets of survey questions, the standard
      YRBSS questions produced estimates and percentages that were most consistently
      closest to 24-hour dietary recall interview estimates. CONCLUSIONS: For brief
      self-administered questionnaires of high school students, the current YRBSS
      questions are recommended for monitoring F/V intake even though mean intake
      estimates in times/day will likely be higher than, and are not a proxy for, mean
      intake estimates in servings/day.

PMID- 23871105
TI  - Diet quality of overweight and obese mothers and their preschool children.
AB  - BACKGROUND: Children of obese parents are more likely to become obese than
      children of normal-weight parents. However, there is little information regarding
      the diet intakes of children of obese parents. OBJECTIVE: Our objective was to
      determine the diet quality of preschoolers and their overweight/obese mothers,
      whether maternal and child diet quality were correlated, and predictors of
      child's diet quality. DESIGN: Results are from baseline measurements from a
      randomized controlled behavioral intervention. PARTICIPANTS: Participants were
      English-literate, postpartum mothers and their preschoolers (n=177 mother-child
      dyads) in North Carolina. Visits took place in the Triangle and Triad regions of
      North Carolina between September 2007 and November 2009. MAIN OUTCOME MEASURES:
      We measured diet quality of mothers and preschoolers using the Healthy Eating
      Index-2005. STATISTICAL ANALYSES PERFORMED: Descriptive statistics, chi(2),
      analysis of variance, Pearson correlations, and stepwise regression models were
      used. RESULTS: Only 11% of children and 7% of mothers had Healthy Eating Index
      2005 scores >=80. Most children did not meet recommendations for fruits,
      vegetables, whole grains, meat and beans, sodium, saturated fat, and energy from
      solid fat and added sugars. Child diet quality was correlated with maternal diet
      quality (r=0.44; P<0.001). However, children and mothers differed in the
      proportion that met food-group recommendations: children vs mothers: total fruit
      (50% vs 14%), whole fruit (46% vs 28%), total vegetables (6% vs 18%), dark green
      and orange vegetables and legumes (7% vs 19%), total grains (57% vs 71%), milk
      (63% vs 22%), and meat and beans (33% vs 60%). Maternal diet quality and
      household income were positively correlated with child diet quality. CONCLUSIONS:
      The diets of children of overweight/obese mothers need improvement in several
      areas. Mother's diet quality and household income are important contributors to
      child's diet quality and should be considered in efforts to improve the diets of
      these children.

PMID- 23871106
TI  - A qualitative study of motivators and barriers to healthy eating in pregnancy for
      low-income, overweight, African-American mothers.
AB  - Poor diet quality is common among low-income, overweight, African-American
      mothers, placing them at high risk for adverse pregnancy outcomes. We sought to
      better understand the contextual factors that may influence low-income African
      American mothers' diet quality during pregnancy. In 2011, we conducted semi
      structured interviews with 21 overweight/obese, pregnant African Americans in
      Philadelphia, PA, all of whom received Medicaid and were eligible for the Special
      Supplemental Nutrition Program for Women, Infants, and Children. Two readers
      independently coded the interview transcripts to identify recurrent themes. We
      identified 10 themes around motivators and barriers to healthy eating in
      pregnancy. Mothers believed that consuming healthy foods, like fruits and
      vegetables, would lead to healthy babies and limit the physical discomforts of
      pregnancy. However, more often than not, mothers chose foods that were high in
      fats and sugars because of taste, cost, and convenience. In addition, mothers had
      several misconceptions about the definition of healthy (eg, "juice is good for
      baby"), which led to overconsumption. Many mothers feared they might "starve"
      their babies if they did not get enough to eat, promoting persistent snacking and
      larger portions. Living in multigenerational households and sharing resources
      also limited the mothers' control over food choices and made consuming healthy
      foods especially difficult. Despite the good intentions of low-income African
      American mothers to improve diet quality during pregnancy, multiple factors
      worked together as barriers to healthy eating. Interventions that emphasize tasty
      and affordable healthy food substitutes, address misconceptions, and counsel
      mothers about true energy needs in pregnancy may improve low-income, African
      American, overweight/obese mothers' diet quality. 

PMID- 23871107
TI  - Business list vs ground observation for measuring a food environment: saving time
      or waste of time (or worse)?
AB  - In food-environment research, an alternative to resource-intensive direct
      observation on the ground has been the use of commercial business lists. We
      sought to determine how well a frequently used commercial business list measures
      a dense urban food environment like the Bronx, NY. On 155 Bronx street segments,
      investigators compared two different levels for matches between the business list
      and direct ground observation: lenient (by business type) and strict (by business
      name). For each level of matching, researchers calculated sensitivities and
      positive predictive values (PPVs) for the business list overall and by broad
      business categories: General Grocers (eg, supermarkets), Specialty Food Stores
      (eg, produce markets), Restaurants, and Businesses Not Primarily Selling Food
      (eg, newsstands). Even after cleaning the business list (eg, for cases of
      multiple listings at a single location), and allowing for inexactness in listed
      street addresses and spellings of business names, the overall performance of the
      business list was poor. For strict matches, the business list had an overall
      sensitivity of 39.3% and PPV of 45.5%. Sensitivities and PPVs by broad business
      categories were not meaningfully different from overall values, although
      sensitivity for General Grocers and PPV for Specialty Food Stores were
      particularly low: 26.2% and 32%, respectively. For lenient matches, sensitivities
      and PPVs were somewhat higher but still poor: 52.4% to 60% and 60% to 75%,
      respectively. The business list is inadequate to measure the actual food
      environment in the Bronx. If results represent performance in other settings,
      findings from prior studies linking food environments to diet and diet-related
      health outcomes using such business lists are in question, and future studies of
      this type should avoid relying solely on such business lists. 

PMID- 23871108
TI  - Cross-border use of food databases: equivalence of US and Australian databases
      for macronutrients.
AB  - When estimating dietary intake across multiple countries, the lack of a single
      comprehensive dietary database may lead researchers to modify one database to
      analyze intakes for all participants. This approach may yield results different
      from those using the country-specific database and introduce measurement error.
      We examined whether nutrient intakes of Australians calculated with a modified US
      database would be similar to those calculated with an Australian database. We
      analyzed 3-day food records of 68 Australian adults using the US-based Nutrition
      Data System for Research, modified to reflect food items consumed in Australia.
      Modification entailed identifying a substitute food whose energy and
      macronutrient content were within 10% of the Australian food or by adding a new
      food to the database. Paired Wilcoxon signed rank tests were used to compare
      differences in nutrient intakes estimated by both databases, and Pearson and
      intraclass correlation coefficients measured degree of association and agreement
      between intake estimates for individuals. Median intakes of energy, carbohydrate,
      protein, and fiber differed by <5% at the group level. Larger discrepancies were
      seen for fat (11%; P<0.0001) and most micronutrients. Despite strong
      correlations, nutrient intakes differed by >10% for an appreciable percentage of
      participants (35% for energy to 69% for total fat). Adding country-specific food
      items to an existing database resulted in similar overall macronutrient intake
      estimates but was insufficient for estimating individual intakes. When analyzing
      nutrient intakes in multinational studies, greater standardization and
      modification of databases may be required to more accurately estimate intake of
      individuals. 

PMID- 23871109
TI  - A novel approach for increasing fruit consumption in children.
AB  - Despite the well-documented health benefits of fruits and vegetables and the
      public health campaigns promoting their consumption, children's intake is below
      the recommended levels. A randomized controlled trial for evaluating the
      effectiveness of a school-based intervention for increasing children's fruit
      intake, with the teacher being the exposure model, was designed. Two hundred
      eighteen elementary school students (aged 9 years) in Cyprus were randomly
      assigned into two 1-year intervention groups, the Educational Material group
      (EDUC) (n=59) and the Exposure group (EXPO) (n=67), or a control group (n=58).
      Children's dietary intake was assessed through 2-day dietary records before the
      intervention began (October 2008), at the end of the intervention (June 2009),
      and at 1-year follow-up (June 2010). Students in the EDUC group received a weekly
      educational program for increasing awareness and improving skills regarding fruit
      preparation/consumption and students in the EXPO group were exposed to the
      consumption of a fruit on a daily basis by their teacher. The control group
      members received no intervention. Repeated measures analysis of variance was used
      to evaluate the group effect and the time*group interaction. Higher fruit intake
      was reported by the children in the EXPO and the EDUC groups compared with the
      control group at the end of the intervention: a statistically significant group
      effect was found (P<0.001). At 1-year follow-up, results remained significant
      only for the children in the EXPO group (P<0.001). Exposure to fruit consumption
      by schoolteachers may be a more effective way for improving fruit intake of
      children compared with traditional educational approaches. 

PMID- 23871110
TI  - Barriers and facilitators for consumer adherence to the dietary guidelines for
      Americans: the HEALTH study.
AB  - The majority of the US population does not meet recommendations for consumption
      of milk, whole grains, fruit, and vegetables. The goal of our study was to
      understand barriers and facilitators to adherence to the Dietary Guidelines for
      Americans for four nutrient-rich food groups in fifth-grade children and
      unrelated adult caregivers across six sites in a multistate study. A total of 281
      unrelated adult caregivers (32% African American, 33% European American, and 35%
      Hispanic American) and 321 children (33% African American, 33% European American,
      and 34% Hispanic American) participated in 97 Nominal Group Technique sessions.
      Nominal Group Technique is a qualitative method of data collection that enables a
      group to generate and prioritize a large number of issues within a structure that
      gives everyone an equal voice. The core barriers specific to unrelated adult
      caregivers were lack of meal preparation skills or recipes (whole grains, fruit,
      vegetables); difficulty in changing eating habits (whole grains, fruit,
      vegetables), cost (milk, whole grains, fruit, vegetables), lack of knowledge of
      recommendation/portion/health benefits (milk, vegetables), and taste (milk, whole
      grains, vegetables). Specific to children, the core barriers were competing foods
      (ie, soda, junk foods, sugary foods [whole grains, milk, fruit, vegetables]),
      health concerns (ie, milk allergy/upset stomach [milk]), taste/flavor/smell
      (milk, whole grains, fruit, vegetables), forget to eat them (vegetables, fruit),
      and hard to consume or figure out the recommended amount (milk, fruit). For both
      unrelated adult caregivers and children, reported facilitators closely coincided
      with the barriers, highlighting modifiable conditions that could help individuals
      to meet the Dietary Guidelines for Americans. 

PMID- 23871111
TI  - A relay mechanism between EB1 and APC facilitate STIM1 puncta assembly at
      endoplasmic reticulum-plasma membrane junctions.
AB  - The assembly of STIM1 protein puncta near endoplasmic reticulum-plasma membrane
      (ER-PM) junctions is required for optimal activation of store-operated channels
      (SOC). The mechanisms controlling the translocation of STIM1 puncta to ER-PM
      junctions remain largely unknown. In the present study, we have explored the role
      of the microtubule binding protein adenomatous polyposis coli (APC), on STIM1
      puncta and store-operated calcium entry (SOCE). APC-depleted cells showed reduced
      STIM1 puncta near ER-PM junctions, instead puncta is found at the ER surrounding
      the cell nucleus. Reduced STIM1 puncta near ER-PM junctions in APC-depleted cells
      correlates with a strong inhibition of SOCE and diminished Orai whole-cell
      currents. Immunoprecipitation and confocal microscopy co-localization studies
      indicate that, upon depletion of the ER, STIM1 dissociates from EB1 and
      associates to APC. Deletion analysis identified an APC-binding domain in the
      carboxyl terminus of STIM1 (STIM1 650-685). These results together position APC
      as an important element in facilitating the translocation of STIM1 puncta near ER
      PM junctions, which in turn is required for efficient SOCE and Orai activation
      upon depletion of the ER.

PMID- 23871112
TI  - Corneal endothelial cell loss and corneal thickness in conventional compared with
      femtosecond laser-assisted cataract surgery: three-month follow-up.
AB  - PURPOSE: To quantify changes in endothelial cell counts and corneal thickness
      measurements in patients having standard phacoemulsification compared with
      femtosecond laser-assisted cataract removal. SETTING: Ruhr University Eye Clinic,
      Bochum, Germany. DESIGN: Prospective randomized intraindividual cohort study.
      METHODS: One eye of each patient had standard phacoemulsification (control group)
      and the other eye had femtosecond laser-assisted phacoemulsification (study
      group), both with intraocular lens implantation. Pulsed ultrasound energy was
      used for phacoemulsification. Noncontact endothelial cell microscopy and corneal
      pachymetry were performed preoperatively and 1 day, 3 to 4 days, 7 to 10 days, 50
      to 60 days, and 90 to 100 days postoperatively. RESULTS: The mean endothelial
      cell loss was 7.9% +/- 7.8% (SD) 1 week postoperatively and 8.1% +/- 8.1% 3
      months postoperatively in the study group and 12.1% +/- 7.3% and 13.7% +/- 8.4%,
      respectively, in the control group. The mean relative change in corneal thickness
      from the preoperative values was -0.0% +/- 1.9% at 1 day, 2.8% +/- 1.8% at 1
      week, and 3.3% +/- 1.7% at 3 months in the study group and -0.9% +/- 2.3%, 2.4%
      +/- 1.5%, and 3.2% +/- 1.4%, respectively, in the control group. CONCLUSION: The
      femtosecond laser did not add to the endothelial damage caused by cataract
      surgery and might be beneficial in eyes with low preoperative endothelial cell
      values (eg, cornea guttata cases).

PMID- 23871113
TI  - Axial myopic progression following phakic intraocular lens implantation.
AB  - A 45-year-old woman presented to her ophthalmologist complaining of worsening
      uncorrected distance visual acuity following placement of an Implantable Collamer
      Lens phakic intraocular lens (pIOL) approximately 10 years earlier. Prior to the
      pIOL surgery, contact ultrasound axial length (AL) measurements of 28.28 mm in
      the right eye and 27.90 mm in the left eye indicated the presence of axial
      myopia. At review 10 years after the initial pIOL surgery, the AL measured by
      partial coherence interferometry had increased to 30.25 mm and 29.22 mm,
      respectively, indicating a progression of the axial myopia. This case suggests
      that in some patients, age and recent myopic stability are insufficient criteria
      to conclude that the high myopia is nonprogressive. In our patient, placement of
      a pIOL and induction of a stable, constant, and focused foveal image were not
      sufficient to prevent further axial myopic progression. FINANCIAL DISCLOSURE: No
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 23871114
TI  - Subjective age and cognitive functioning: a 10-year prospective study.
AB  - OBJECTIVES: The present study examines whether subjective age (i.e., how old or
      young individuals feel) is associated with cognitive functioning and tests
      potential mediators of this association. DESIGN: Data from the two waves of
      measurement of the Midlife in the United States survey were used, with
      assessments conducted at the first wave in 1994-1995 and at the second wave in
      2004-2006. PARTICIPANTS: A total of 1,352 men and women aged from 50 to 75 years
      at baseline (M: 59.32; SD: 6.72). MEASUREMENTS: Subjective age, body mass index
      (BMI), physical activity, and the covariates sex, age, education, marital status,
      and disease burden were assessed at baseline to predict episodic memory and
      executive function measured 10 years later. RESULTS: Multiple regression analysis
      revealed that a younger subjective age at baseline was prospectively associated
      with better episodic memory and executive function. Bootstrap analysis indicated
      that the association of subjective age with episodic memory and executive
      function was partially mediated by BMI and frequency of physical activity
      respectively. CONCLUSION: Even after accounting for chronological age and other
      risk factors for cognitive decline, such as disease burden and sedentary
      lifestyle, the subjective experience of aging predicts cognitive functioning in
      old age.

PMID- 23871115
TI  - Unmet needs and health-related quality of life in young-onset dementia.
AB  - OBJECTIVES: Young-onset dementia (YOD) causes specific challenges and issues that
      are likely to affect health-related quality of life (HRQOL). This study explored
      patient and caregiver HRQOL and its association with unmet needs in YOD. METHODS:
      A cross-sectional design was used to study 215 community-dwelling YOD patients
      and their primary caregivers. Multiple linear regression analyses were performed
      to determine the relationship between unmet needs assessed with the Camberwell
      Assessment of Need for the Elderly scale and patient and caregiver HRQOL,
      controlling for other variables such as demographic characteristics, patient
      functional status, neuropsychiatric symptoms, and caregiver sense of competence.
      RESULTS: Patient HRQOL was not associated with unmet needs. However, we found
      that the unmet needs of both patient and caregiver were related to several
      domains of caregiver HRQOL. CONCLUSIONS: This study shows that patient and
      caregiver unmet needs are related to caregiver HRQOL in YOD. However, the
      relationship between HRQOL and unmet needs is complex. The assessment of unmet
      needs within the context of HRQOL seems to be an important prerequisite for
      personalizing care in YOD. Adjusting supportive services to match the individual
      needs and preferences of these young patients and their caregivers is likely to
      enhance their quality of life.

PMID- 23871116
TI  - Depression among stroke survivors: a community-based, prospective study from
      Kolkata, India.
AB  - OBJECTIVE: Post-stroke depression (PSD) is a disabling entity among stroke
      survivors (SS). Longitudinal studies on PSD, essential to determine its
      prognosis, are lacking from developing countries. This prospective study was
      undertaken to assess the prevalence, natural history, and correlates of
      depression among SS in an Indian community. METHODS: From a community based
      stroke registry, SS were assessed annually for cognition, disability, and
      depression using Bengali validated scales. PSD was diagnosed if score on
      geriatric depression scale was greater than or equal to 21. Complex sample
      strategy was considered when calculating prevalence of post stroke depression. An
      age- and sex-matched case-control study was undertaken to determine the odds of
      depression in SS. RESULTS: Prevalence of PSD was 36.98% (95% confidence interval
      [CI]: 31.89%-42.06%) among 241 patients assessed at baseline. About 17% developed
      depression annually and a similar proportion had spontaneous improvement. Peak
      rate of PSD was beyond 3 months and continued up to 18 months after stroke.
      Compared to the non-depressed group, PSD subjects were significantly older, had
      higher age at first stroke, less education, lower socioeconomic status, and
      greater cognitive impairment and disability. Education had a protective role.
      Mortality in PSD was nearly twice that in non-depressed patients, though not
      significant statistically (hazard ratio: 1.84; 95% CI: 0.90-3.77). Compared with
      controls, odds ratio of PSD was 19.95 (95% CI: 10.09-39.47). CONCLUSIONS:
      Approximately one-third of SS develop PSD, similar to developed countries.
      Prevalence remains stable annually. Delayed peak of PSD suggested later
      realization of underlying disability. Predictors of PSD have been described and
      higher literacy was protective in this study.

PMID- 23871117
TI  - A novel rating scale for the measurement of apathy in institutionalized persons
      with dementia: the APADEM-NH.
AB  - OBJECTIVE: Apathy is one of the most frequent symptoms of dementia, still needing
      better measurement methods. The objective of this study was to validate a new
      scale for apathy in institutionalized persons with dementia (APADEM-NH). METHODS:
      The scale includes 26 items distributed in three dimensions: Deficit of Thinking
      and Self-Generated behaviors (DT): 13 items, Emotional Blunting (EB): 7 items,
      and Cognitive Inertia (CI): 6 items. The sample included 100 institutionalized
      patients (90% female) with probable Alzheimer disease (AD) (57%), possible AD
      (13%), AD + cerebral vascular disease (17%), Lewy body dementia (11%), and
      Parkinson associated to dementia (2%), covering all stages of dementia severity
      according to the Global Deterioration Scale and Clinical Dementia Rating.
      Additional assessments were the Apathy Inventory, Neuropsychiatric Inventory,
      Cornell Scale for Depression, and the tested scale. Re-test and inter-rater
      reliability were carried out in 50 patients. RESULTS: All subscales lacked
      relevant floor and ceiling effects (<15%). Internal consistency for each
      dimension was (Cronbach's alpha): DT = 0.88, EB = 0.83, CI = 0.88; item-total
      correlations were >0.40; and item homogeneity 0.36-0.51. Test-retest reliability
      for the items was kW = 0.48-0.92; for the subscales, intraclass correlation
      coefficient (ICC) = 0.80-0.88; and for the total score, ICC = 0.90. Inter-rater
      reliability reached kW values of 0.84-1.00; subscales ICC, 0.97-0.99, and total
      score ICC, 0.99. Standard error of measurement for total score was 6.41 and
      internal validity ranged from rS = 0.69-0.80. CONCLUSIONS: APADEM-NH proved to be
      feasible, reliable, and valid for apathy assessment in institutionalized patients
      suffering mild to severe dementia, discerning well between apathy and depression.

PMID- 23871119
TI  - Personality type as a predictor for depressive symptoms and reduction in quality
      of life among stroke survivals.
AB  - OBJECTIVE: Although poststroke depression (PSD) and reduction in quality of life
      (QOL) are prevalent among stroke patients, little is known about the contribution
      of personality traits to such impairments. This study examines whether particular
      personality traits predict PSD symptoms (PSDS) and reduction in QOL among stroke
      survivals using Cloninger's biopsychosocial personality model. We hypothesized
      that harm avoidance (HA), expressing the tendency to respond intensely to adverse
      stimuli, characterizes stroke survivors at risk for PSDS and reduction in QOL.
      METHODS: Hospitalized stroke patients (N = 84, age 63.5 +/- 9.7 years)
      prospectively completed Cloninger's Tridimensional Personality Questionnaire,
      defining HA dominancy by scoring the three personality dimensions: reward
      dependence, novelty seeking, and HA. The level of neurologic deficit was
      evaluated by the National Institutes of Health Stroke Scale. At the 3-month
      follow-up visit, depressive symptoms and QOL scores were assessed using the Beck
      Depression Inventory and the Stroke Specific Quality of Life questionnaire.
      RESULTS: Regression analyses revealed that higher HA scores independently
      predicted PSDS and reduction in QOL. After controlling for the relative
      contribution of stroke type and health-related variables, HA and neurologic
      deficit were significant risk factors for poststroke negative outcomes.
      CONCLUSION: Our findings emphasize the relevance of Cloninger's theory
      (manifested by individual HA behavior) as a distinctive means to identifying
      patients at risk for PSDS and lower QOL after stroke. The role of specific
      psychological and neurologic aspects involved in the mechanism of PSD should be
      further explored using biopsychosocial models.

PMID- 23871118
TI  - Longitudinal relationships between Alzheimer disease progression and psychosis,
      depressed mood, and agitation/aggression.
AB  - OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are
      prevalent in Alzheimer disease (AD) and are related to poor outcomes such as
      nursing home placement. No study has examined the impact of individual BPSD on
      dependence, a clinically important feature that reflects changing patient needs
      and their effect on caregivers. The current study characterized independent cross
      sectional and longitudinal relationships between three BPSD (psychosis, depressed
      mood, and agitation/aggression), cognition, and dependence to better understand
      the interplay between these symptoms over time. DESIGN: The Predictors Study
      measured changes in BPSD, cognition, and dependence every 6 months in patients
      with AD. Cross-sectional and longitudinal relationships between individual BPSD,
      cognition, and dependence over 6 years were characterized by using multivariate
      latent growth curve modeling. This approach characterizes independent changes in
      multiple outcome measures over time. SETTING: Four memory clinics in the United
      States and Europe. PARTICIPANTS: A total of 517 patients with probable AD.
      MEASUREMENTS: Columbia University Scale for Psychopathology, modified Mini-Mental
      State Examination, and Dependence Scale. RESULTS: Both psychosis and depressed
      mood at study entry were associated with worse subsequent cognitive decline.
      Independent of cognitive decline, initial psychosis was associated with worse
      subsequent increases in dependence. Rates of increase in agitation/aggression
      separately correlated with rates of declines in both cognition and independence.
      CONCLUSIONS: Although purely observational, our findings support the poor
      prognosis associated with psychosis and depression in AD. Results also show that
      agitation/aggression tracks declines in cognition and independence independently
      over time. Targeted intervention for individual BPSD, particularly psychosis,
      could have broad effects not only on patient well-being but also on care costs
      and family burden.

PMID- 23871120
TI  - A randomized cross-over controlled study on cognitive rehabilitation of
      instrumental activities of daily living in Alzheimer disease.
AB  - OBJECTIVE: The goal of the study was to investigate the effectiveness of a memory
      rehabilitation program to re-learn instrumental activities of daily living
      (IADLs) in patients with Alzheimer disease (AD). DESIGN: This was a 6-month block
      randomized cross-over controlled study. SETTING: All evaluation and training
      sessions were performed at each patient's home. PARTICIPANTS: Twenty participants
      with mild to moderate AD. INTERVENTION: The trained IADL was chosen by the
      patient and his/her caregiver in order to target the patient's needs and
      interests. Participants were trained twice a week for 4 weeks with the errorless
      learning (ELL) and spaced retrieval (SR) cognitive techniques. After training,
      there were several follow-ups over a period of at least 3 months. MEASUREMENTS:
      Performance on the trained IADL was assessed by a Direct Measure of Training
      (DMT), an observational instrument adapted from a well-validated scale. General
      cognitive function, everyday memory functioning, quality of life,
      neuropsychiatric symptoms and ADL/IADL of patients, as well as the caregiver's
      burden were assessed as secondary outcomes. RESULTS: A statistical significant
      difference was found between the trained and untrained groups on the DMT
      immediately following the intervention. Improvements were maintained for a 3
      month period. The training did not have effects on any other measures.
      CONCLUSIONS: The present study showed that it is possible for AD patients to
      relearn significant IADLs with the ELL and SR techniques and to maintain these
      gains during at least 3 months. The findings of this study emphasize the
      importance to design robust but individualized intervention tailored on patients'
      particular needs.

PMID- 23871121
TI  - Kenya's health workforce information system: a model of impact on strategic human
      resources policy, planning and management.
AB  - OBJECTIVE: Countries worldwide are challenged by health worker shortages, skill
      mix imbalances, and maldistribution. Human resources information systems (HRIS)
      are used to monitor and address these health workforce issues, but global
      understanding of such systems is minimal and baseline information regarding their
      scope and capability is practically non-existent. The Kenya Health Workforce
      Information System (KHWIS) has been identified as a promising example of a
      functioning HRIS. The objective of this paper is to document the impact of KHWIS
      data on human resources policy, planning and management. METHODS: Sources for
      this study included semi-structured interviews with senior officials at Kenya's
      Ministry of Medical Services (MOMS), Ministry of Public Health and Sanitation
      (MOPHS), the Department of Nursing within MOMS, the Nursing Council of Kenya,
      Kenya Medical Practitioners and Dentists Board, Kenya's Clinical Officers
      Council, and Kenya Medical Laboratory Technicians and Technologists Board.
      Additionally, quantitative data were extracted from KHWIS databases to supplement
      the interviews. Health sector policy documents were retrieved from MOMS and MOPHS
      websites, and reviewed to assess whether they documented any changes to policy
      and practice as having been impacted by KHWIS data. RESULTS: Interviews with
      Kenyan government and regulatory officials cited health workforce data provided
      by KHWIS influenced policy, regulation, and management. Policy changes include
      extension of Kenya's age of mandatory civil service retirement from 55 to 60
      years. Data retrieved from KHWIS document increased relicensing of professional
      nurses, midwives, medical practitioners and dentists, and interviewees reported
      this improved compliance raised professional regulatory body revenues. The review
      of Government records revealed few references to KHWIS; however, documentation
      specifically cited the KHWIS as having improved the availability of human
      resources for health information regarding workforce planning, management, and
      development. CONCLUSION: KHWIS data have impacted a range of improvements in
      health worker regulation, human resources management, and workforce policy and
      planning at Kenya's ministries of health.

PMID- 23871122
TI  - Rates of anterior cervical discectomy and fusion after initial posterior cervical
      foraminotomy.
AB  - BACKGROUND CONTEXT: In select patients, posterior cervical foraminotomy (PCF) and
      anterior cervical discectomy and fusion (ACDF) result in similar clinical
      outcomes when used to treat cervical radiculopathy. Nonetheless, ACDF is
      performed more frequently, in part because of surgeon perception that PCF
      requires operative revisions more frequently. The present study investigates the
      rate of ACDF reoperation at the index level after initial PCF. PURPOSE: To
      determine the rate of ACDF after initial PCF and to further describe any patient
      characteristics or preoperative or operative data that increase the rate of
      reoperation after PCF. STUDY DESIGN: Retrospective chart review. METHODS:
      Demographic, operative, and reoperation information was collected from the
      electronic medical records for all patients who underwent PCF at one institution
      between 2004 and 2011. All patients were subsequently contacted by telephone to
      identify postoperative complications and more conclusively determine whether any
      revision operation was performed at the index level. RESULTS: One hundred seventy
      eight patients who underwent a PCF were reviewed, with an average follow-up of
      31.7 months. Nine (5%) patients underwent an ACDF revision operation at the index
      level. The reason for reoperation in these patients included cervical
      radiculopathy, foraminal stenosis, disc herniation, and cervical spondylosis.
      Patients who subsequently underwent ACDF at the index level were significantly
      younger (25 vs. 35 years, p=.03), had lower body mass index (25 vs. 29, p=.01),
      and more likely to take anxiolytic (56% vs. 22%, p=.04) or antidepressant
      medication (67% vs. 27%, p=.02), compared with those that did not have a revision
      operation. CONCLUSIONS: This is the first study to determine conversion to ACDF
      after PCF. The present study demonstrates that PCF is associated with a low
      reoperation rate, similar to the historical reoperation for ACDF. Accordingly,
      spine surgeons can operate via a PCF approach without a significant increased
      risk for ACDF revision surgery at the index level.

PMID- 23871124
TI  - Evidence-based physical activity guidelines for cancer survivors: current
      guidelines, knowledge gaps and future research directions.
AB  - Physical activity during and after cancer treatment has beneficial effects on a
      number of physical and psychosocial outcomes. This paper aims to discuss the
      existing physical activity guidelines for cancer survivors and to describe future
      research directions to optimize prescriptions. Studies on physical activity
      during and after cancer treatment were searched in PubMed, Clinicaltrials.gov,
      Australian New Zealand Clinical Trials Registry, and Dutch Trial registry.
      Physical activity guidelines for cancer survivors suggest that physical activity
      should be an integral and continuous part of care for all cancer survivors.
      However, the development of these guidelines has been limited by the research
      conducted. To be able to develop more specific guidelines, future studies should
      focus on identifying clinical, personal, physical, psychosocial, and intervention
      moderators explaining 'for whom' or 'under what circumstances' interventions
      work. Further, more insight into the working mechanisms of exercise interventions
      on health outcomes in cancer survivors is needed to improve the efficacy and
      efficiency of interventions. Finally, existing programs should embrace interests
      and preferences of patients to facilitate optimal uptake of interventions. In
      conclusion, current physical activity guidelines for cancer survivors are
      generic, and research is needed to develop more personalized physical activity
      guidelines.

PMID- 23871123
TI  - Rare lysosomal enzyme gene SMPD1 variant (p.R591C) associates with Parkinson's
      disease.
AB  - To investigate the role of mutations in the sphingomyelin phosphodiesterase
      (SMPD1) gene in Parkinson's disease (PD) we sequenced all the exons of this gene
      in 198 Chinese PD cases and matched healthy control subjects. We identified 4
      rare variants in SMPD1 (p.P332R, p.Y500H, p.P533L, and p.R591C) that were present
      only in cases and not in control subjects. Interestingly, 2 of these variants
      were previously reported in Chinese Niemann-Pick disease patients. Next, we
      genotyped these variants in another 806 PD cases and 7481 control subjects. We
      identified a novel, rare SMPD1 variant (p.R591C) which increased the risk of PD
      (p = 0.009). 

PMID- 23871125
TI  - Bioactive acetylenic metabolites.
AB  - This article focuses on anticancer, and other biological activities of acetylenic
      metabolites obtained from plants and fungi. Acetylenic compounds belong to a
      class of molecules containing triple bond(s). Naturally occurring acetylenics are
      of particular interest since many of them display important biological activities
      and possess antitumor, antibacterial, antimicrobial, antifungal, and
      immunosuppressive properties. There are of great interest for medicine,
      pharmacology, medicinal chemistry, and pharmaceutical industries. This review
      presents structures and describes cytotoxic activities of more than 100
      acetylenic metabolites, including fatty alcohols, ketones, and acids, acetylenic
      cyclohexanoids, spiroketal enol ethers, and carotenoids isolated from fungi and
      plants. 

PMID- 23871126
TI  - Cognitive performance is impaired in euthymic Chinese patients with Bipolar 1
      Disorder.
AB  - BACKGROUND: Data from euthymic patients with Bipolar Disorder (BD) has shown
      cognitive impairment and the notion that sufferers of BD achieve full recovery
      between illness episodes is questionable. These findings have not been replicated
      in a Chinese population. The present study examined the cognitive profile of
      euthymic Chinese patients with Bipolar 1 Disorder (BD-1) and matched healthy
      control participants. METHODS: Euthymic patients with BD-1 and matched controls
      (n=104 in total) completed serial measures to assess mood and also completed an
      IQ test and the Central Nervous System Vital Signs (CNSVS) computerized battery
      assessing memory (verbal and visual), executive functions, attention, psychomotor
      and processing speed. RESULTS: Patients with BD-1 performed worse than controls
      on all cognitive domains. When using 2 or more scores below the 5th percentile as
      a cutoff for neurocognitive impairment, 46.2% of the patients with BD-1 and none
      of the control sample scored in this range (p<.001). Correlational analysis among
      the illness variables in BD-1 revealed that cognitive performance was inversely
      correlated with the number of manic episodes and duration of illness.
      LIMITATIONS: It was not possible to determine the causal relationship between
      associated illness and performance. The effect of medication on cognitive
      performance requires further study. CONCLUSIONS: Euthymic Chinese patients with
      BD-1 demonstrate marked cognitive impairments and these correlated with illness
      parameters. Cognitive impairment in BD may be independent of language and
      culture.

PMID- 23871127
TI  - A pilot randomized controlled trial of a depression and disease management
      program delivered by phone.
AB  - BACKGROUND: Depression in medically ill patients occurs at twice the rate found
      in the general population. Though pharmacologic and psychotherapeutic
      interventions for depression are effective, response to treatment and access to
      care are barriers for this population. A multidimensional telehealth intervention
      was designed to focus on these barriers by delivering a phone based intervention
      that addressed managing one's illness and coping emotionally. METHODS: Veterans
      with diabetes, hypertension, or chronic pain and depressive symptoms were
      randomized to one of three conditions: Usual Care (n=23), Illness Management Only
      (n=31), or Combined Psychotherapy and Illness Management (n=29). Those randomized
      to the Combined or Illness Management Only intervention group received 10 phone
      visits. Veterans in the Combined group received all aspects of the illness
      management program plus a manualized depression intervention. Subjects completed
      assessments at baseline, week 5, and 10 to test the main hypothesis that veterans
      in the Combined condition would have a greater decline in depressive symptoms.
      RESULTS: The Combined intervention yielded a significant decline in depressive
      symptoms when compared with Usual Care. However, the there was no significant
      difference between the Combined and Illness Management Only groups. LIMITATIONS:
      This is a pilot study with a small sample size relative to a standard randomized
      controlled trial in psychotherapy. CONCLUSIONS: This telephone-based intervention
      succeeded in reducing depressive symptoms in veterans with chronic illness. It
      adds to the building evidence base for providing phone-delivered mental health
      services.

PMID- 23871128
TI  - Affect recognition across manic and euthymic phases of bipolar disorder in Han
      Chinese patients.
AB  - Patients with bipolar disorder (BD) have affect recognition deficits. Whether
      affect recognition deficits constitute a state or trait marker of BD has great
      etiopathological significance. The current study aims to explore the
      interrelationships between affect recognition and basic neurocognitive functions
      for patients with BD across different mood states, using the Diagnostic Analysis
      of Non-Verbal Accuracy-2, Taiwanese version (DANVA-2-TW) as the index measure for
      affect recognition. To our knowledge, this is the first study examining affect
      recognition deficits of BPD across mood states in the Han Chinese population.
      Twenty-nine manic patients, 16 remitted patients with BD, and 40 control subjects
      are included in the study. Distinct association patterns between affect
      recognition and neurocognitive functions are demonstrated for patients with BD
      and control subjects, implicating alternations in emotion associated
      neurocognitive processing. Compared to control subjects, manic patients but not
      remitted subjects perform significantly worse in the recognition of negative
      emotions as a whole and specifically anger, after adjusting for differences in
      general intellectual ability and basic neurocognitive functions. Affect
      recognition deficit may be a relatively independent impairment in BD rather than
      consequences arising from deficits in other basic neurocognition. The impairments
      of manic patients in the recognition of negative emotions, specifically anger,
      may further our understanding of core clinical psychopathology of BD and have
      implications in treating bipolar patients across distinct mood phases.

PMID- 23871129
TI  - Depression and its risk factors among pregnant women in 2008 Sichuan earthquake
      area and non-earthquake struck area in China.
AB  - BACKGROUND: On May 12, 2008, a powerful 8.0 magnitude earthquake struck China's
      Sichuan province. While some studies have assessed the mental and physical
      wellbeing of disaster victims, few have examined the long-term impact of natural
      disasters on pregnant women's mental health. As such, this study aims to assess
      whether the Sichuan earthquake continues to negatively affect women's mental
      health, 4 years since its occurrence. In addition, predictive and protective risk
      factors of depressive symptoms among pregnant women were also identified.
      METHODS: From June 2012 to October 2012, 520 pregnant women were interviewed, of
      whom 253 were from an earthquake struck area and 267 were from a non-earthquake
      struck area. Symptoms of antenatal depression were measured using the Edinburgh
      Postnatal Depression Scale (EPDS) with a cutoff of>=10. RESULTS: The prevalence
      rate of depression among pregnant women in the earthquake area was 34.5% (95% CI,
      28.9-40.6), while the rate in the non-earthquake area was 39.6% (95% CI, 33.9
      45.5). The perceived stresses associated with pregnancy and social support from
      husbands are significantly correlated with antenatal depression. LIMITATIONS:
      Lack of diagnosis for antenatal depression and it is a self-report evaluation.
      CONCLUSIONS: This study found that the Sichuan earthquake does not necessarily
      have a long-lasting effect on pregnant women who were once victims of the
      disaster. It was found that pregnant women who experience high levels of
      pressures from the pregnancy and receive medium support from husbands are more
      susceptible to experience antenatal depression than pregnant women who perceive
      higher levels of support from husbands.

PMID- 23871130
TI  - The impact of structure on elasticity, switchability, stability and functionality
      of an all-in-one carboxybetaine elastomer.
AB  - In this work, we designed and synthesized an all-in-one zwitterionic material
      (poly2-((2-hydroxyethyl)(2-methacrylamidoethyl)(methyl)ammonio)acetate (pCBMAA
      1)) bearing elasticity, switchable antimicrobial/antifouling properties, and
      stability. Zwitterionic materials have drawn special attention due to their
      outstanding antifouling properties; however, conventional zwitterionic materials
      lack tunable elasticity, stability and antimicrobial properties. We addressed
      these challenges by integrating all desired properties into a single zwitterionic
      molecule through rational design. pCBMAA-1 hydrogel showed typical elastomeric
      stress-strain curves with low Young's modulus and high yield strain, in both
      tensile and compression tests. About 65% tensile strain and 85% compressive
      strain were achieved. pCBMAA-1 hydrogel can switch between cationic antimicrobial
      form and zwitterionic antifouling form. In its cationic ring form, pCBMAA-1
      hydrogel killed 99.5% of attached bacterial cells and then released 95% of killed
      cells. pCBMAA-1 surfaces highly resisted the protein adsorption from 100% blood
      plasma and serum. The amount of adsorbed protein was below the detection limit
      (0.3 ng cm(-2)) of the SPR sensor. Compared to existing zwitterionic materials,
      this material showed the dramatically improved stability in both basic and acidic
      conditions. We believe that this all-in-one material will broaden the application
      spectrum of zwitterionic materials to a great extent.

PMID- 23871131
TI  - Gender differences in sexual risk and sexually transmitted infections correlate
      with gender differences in social networks among San Francisco homeless youth.
AB  - PURPOSE: To explore whether gender differences in sexual risk and sexually
      transmitted infections (STIs) among homeless youth may be explained in part by
      gender differences in their social networks. METHODS: Our sample includes 258
      youth (64% male) recruited in San Francisco from street venues and transitional
      programs. Participants completed an audio computer-administered self-interview
      survey regarding their housing status and risk behaviors and an interviewer
      administered survey regarding their social networks, and were tested for STIs
      (chlamydia and gonorrhea). We examined relationships between sexual risk and STI
      rates and social network characteristics by gender. RESULTS: Condom use was lower
      in young women than in young men, whereas young women were more likely to have an
      injection drug user (IDU) sex partner and to be diagnosed with an STI. Homeless
      young men were more likely to have stably housed contacts and same-sex
      friendships in their social networks than were young women. Stably housed network
      contacts were associated with increased condom use and decreased STI prevalence
      in young men. Same-sex friends were associated with increased condom use in young
      women. No young woman with a family member in her network had an IDU sex partner.
      Having a network member who had been recently incarcerated was associated with
      having an IDU sex partner for young women. CONCLUSIONS: Homeless young women's
      networks may place them at greater risk for STIs than young men. Increasing
      mainstream contacts and same-gender friendships may protect all homeless youth
      from STIs. Interventions addressing homeless young women's social networks may
      decrease their gender-disparate STI risk.

PMID- 23871132
TI  - Effect of supplementary calcium phosphate on plasma gastrointestinal hormones in
      a double-blind, placebo-controlled, cross-over human study.
AB  - Gastrointestinal hormones and Ca are associated with bone metabolism. The
      objective of the present human study was to determine the effect of calcium
      phosphate on the postprandial circulation of gastrointestinal hormones. A total
      of ten men participated in the present double-blind, placebo-controlled, cross
      over study. The participants were divided into two groups. Of these, one group
      consumed bread enriched with 1 g Ca (pentacalcium hydroxy-triphosphate, CaP)
      daily for 3 weeks. The other group consumed placebo bread. After 2 weeks of
      washout, the intervention was changed between the groups for another 3 weeks. The
      subjects consumed a defined diet at the beginning (single administration) and at
      the end (repeated administration) of the intervention periods, and blood samples
      were drawn at 0, 30, 60, 120, 180 and 240 min. Between 0 and 30 min, the
      participants consumed a test meal, with or without CaP. The concentrations of
      gastrointestinal hormones (glucose-dependent insulinotropic polypeptide, glucagon
      like peptide (GLP) 1 and GLP2), insulin and glucose were determined. The AUC of
      GLP1 (total and active) and GLP2 increased significantly after the repeated CaP
      administrations compared with that after placebo administration. The AUC of
      insulin and glucose showed no differences between the CaP and placebo
      administrations. CaP affects the postprandial plasma concentrations of
      gastrointestinal hormones through the modulation of the intestinal environment,
      e.g. bile acids and microbiota. 

PMID- 23871134
TI  - Persistent migraine aura in an adolescent girl.
AB  - A 14-year-old girl presented with a prolonged migraine visual aura of several
      weeks' duration. Symptoms gradually resolved over a 6-week period, with no
      recurrence of visual aura over a 20-month follow-up period. Although there is
      significant overlap between the features of stereotypical and persistent migraine
      auras, or "visual snow," the latter tend to be unformed and can occupy the entire
      visual field of both eyes. To our knowledge, this phenomenon has been reported
      only twice before in children. Recognition of its features will allow the
      pediatric ophthalmologist to differentiate persistent visual aura from visual
      hallucinations. 

PMID- 23871133
TI  - The association of the 174G>C polymorphism of interleukin 6 gene with diabetic
      nephropathy in patients with type 2 diabetes mellitus.
AB  - AIMS: To evaluate the association of 174G>C polymorphism on interleukin-6 (IL-6)
      gene with diabetic nephropathy in patients with type 2 diabetes. METHODS: A total
      of 393 Greek subjects with type 2 diabetes (mean age 66.5+/-10.0years, men n=203,
      women n=190) were examined. Diabetic nephropathy was defined as presence of
      microalbuminuria and/or proteinuria. The IL-6 174G>C polymorphism was detected by
      polymerase chain reaction and appropriate restriction enzyme digestion. High
      sensitivity C-reactive protein was assayed by particle-enhanced
      immunonephelometry. RESULTS: The genotype distribution (%) was GG: 49.1, GC: 26.8
      and CC: 24.1, with no gender difference. The CC homozygotes had lower albumin
      excretion (mg/24h) in comparison with the GC genotype [CC: 8.9 (4.0-20.9) vs GC:
      21.95 (9.1-53.35), P=0.004]. Participants with the GC genotype tended to have
      more frequently nephropathy than those with the GG or the CC genotype [GC: 44.55%
      vs GG: 35.1% and CC: 28.3%, P=0.07)]. The CC homozygotes in comparison with GC
      heterozygotes had lower odds to have nephropathy (odds ratio: 0.51, 95%
      confidence intervals=0.28-0.91, P=0.02), even after adjustment for sex, age,
      duration of diabetes, body mass index, smoking, hypertension, lipids and glycated
      hemoglobin, (P=0.01). CONCLUSION: In type 2 diabetes states, CC homozygotes have
      lower albumin excretion and are protected from nephropathy in comparison with GC
      genotypes.

PMID- 23871135
TI  - Bilateral choroidal detachment following cataract surgery in a 40-day-old infant.
AB  - We report a case of bilateral choroidal detachment that occurred shortly after
      uneventful bilateral lensectomy and anterior vitrectomy. B-scan ultrasonography
      showed severe choroidal detachment in the right eye accompanied by limited
      detachment of the overlying retina and mild choroidal effusion in the left eye.
      Two bilateral peribulbar injections of corticosteroid 5 days apart resulted in
      complete resolution of the choroidal effusion in each eye. 

PMID- 23871136
TI  - Conjunctival rhinosporidiosis.
AB  - A 12-year-old boy presenting with redness and foreign body sensation in his right
      eye was found to have a granular, pedunculated mass in the upper palpebral
      conjunctiva near the lid margin. After the mass was excised, the conjunctiva
      healed completely, with mild overlying scarring. At 6 weeks' follow-up, there was
      no evidence of recurrence. Histopathological examination of the mass revealed
      multiple sporangia characteristic of conjunctival rhinosporidiosis. 

PMID- 23871137
TI  - Combined surgical and sclerotherapy for an extensive venous-lymphatic orbital
      anomaly.
AB  - Combined venous-lymphatic anomalies (lymphangiomas) of the orbit are
      nonhereditary, congenital lesions. We report the case of a 6-year-old boy with an
      extensive right orbital venous-lymphatic anomaly and severe facial deformity who
      developed 3 intraconal hemorrhages over 3 months. Although the visual acuity was
      recovered in the first two surgical interventions, the last episode of bleeding
      resulted in permanent visual acuity loss. At that stage, adjunctive therapy with
      n-butyl-cyanoacrylate allowed for greater surgical excision. No further episodes
      of recurrent hemorrhage occurred and the exophthalmos was corrected, thereby
      improving his overall cosmesis. 

PMID- 23871138
TI  - The role of surgical procedures on discriminative performance of the updated
      euroSCORE II.

PMID- 23871139
TI  - Two-ventricle repairs in the unbalanced atrioventricular canal defect spectrum
      with midterm follow-up.
AB  - OBJECTIVES: Unbalanced atrioventricular (AV) canal defects include a hypoplastic
      ventricle (HV) and AV valve (HAVV) precluding complete 2-ventricle repairs
      (2VRs). Catch-up growth would solve this problem and was induced by increasing
      HAVV flow. The objectives were to assess reliability of HV and HAVV growth and
      provide 5- to 15-year 2VR follow-up. METHODS: From 1990 to 2005, 23 consecutive
      infants (13 females and 10 males) with echo-diagnosed unbalanced AV canal defects
      (n = 20) or subsets (n = 3) underwent 2VRs. HV volumes (18 left and 5 right) and
      HAVV sizes estimated from biplane echoes and z values (standard deviation from
      expected) were determined. Hypoplasia was defined by a z value of less than -2.0.
      Three operative approaches were used: (1) Staged repairs (n = 9) had complete AVV
      repairs with partial atrial septal defect and ventricular septal defect closures,
      which increased HAVV flow and maintained stability. The septal defects were
      closed later. (2) An asymmetric valve partition (n = 8) was used to increase HAVV
      size. (3) For moderate hypoplasia, HAVV flow was increased and ASDs/VSDs were
      left for stability (n = 6). Follow-up at 5 to 19 years was done locally. RESULTS:
      Staged repairs began at 20 to 328 days (average, 129 days) and were completed 5
      to 145 days later (average, 101 days). Midterm survival was 87% (20/23) after 1
      central nervous system bleed after trial weaning from extracorporeal membrane
      oxygenation and 2 later deaths from hyperkalemia. Reoperations for AVV
      regurgitation (n = 3), AVV stenosis (n = 1), and mitral valve replacement (n = 1)
      were satisfactory. On follow-up, all hypoplastic structures (HV and HAVV) had
      grown to normal size. Two patients "doing well" were lost to follow-up. Survivors
      have satisfactory 2VRs, with 15 of 18 taking no cardiac failure medications.
      CONCLUSIONS: Reliable HV/HAVV catch-up growth was induced, and all midterm 2VRs
      were satisfactory.

PMID- 23871140
TI  - Process improvement in cardiac surgery: development and implementation of a
      reoperation for bleeding checklist.
AB  - OBJECTIVE: High-performing health care organizations differentiate themselves by
      focusing on continuous process improvement initiatives aimed at enhancing patient
      outcomes. Reoperation for bleeding is an event associated with considerable
      morbidity risk. Hence, our primary objective was to develop and implement a
      formal operative checklist to reduce technical reasons for postoperative
      bleeding. METHODS: From January 1, 2011, through June 30, 2012, 5812 cardiac
      surgical procedures were performed at Cleveland Clinic (Cleveland, OH). A
      multidisciplinary team developed a simple, easy-to-perform hemostasis checklist
      based on the most common sites of bleeding. An extensive educational in-service
      was performed before limited, then universal, checklist implementation. Geometric
      charts were used to track the number of cases between consecutive reoperations
      for bleeding. We compared these before (phase 0) and after the first limited
      implementation phase (phase 1) and the universal implementation phase (phase 2)
      of the checklist. RESULTS: The average number of cases between consecutive
      reoperations for bleeding increased from 32 in phase 0 to 53 in both phase 1 (P =
      .002) and phase 2 (P = .01). CONCLUSIONS: A substantial reduction in reoperation
      for bleeding cases followed implementation of a formalized hemostasis checklist.
      Our findings underscore the important influence of memory aids that focus
      attention on surgical techniques to improve patient outcomes in a complex,
      operative work environment.

PMID- 23871141
TI  - Paracorporeal lung assist device: an innovative surgical strategy for bridging to
      lung transplant in an infant with severe pulmonary hypertension caused by
      alveolar capillary dysplasia.

PMID- 23871142
TI  - Long-term biventricular support with rotary blood pumps in a patient with a
      noncontractile heart.

PMID- 23871143
TI  - Remote ischemic preconditioning impairs ventricular function and increases
      infarct size after prolonged ischemia in the isolated neonatal rabbit heart.
AB  - OBJECTIVES: Remote ischemic preconditioning (rIPC) reduces myocardial injury in
      adults and children undergoing cardiac surgery. We compared the effect of rIPC in
      adult and neonatal rabbits to investigate whether protection against ischemia
      reperfusion injury can be achieved in the newborn heart by (1) in vivo rIPC and
      (2) dialysate from adult rabbits undergoing rIPC. METHODS: Isolated hearts from
      newborn and adult rabbits were randomized into 3 subgroups (control, in vivo
      rIPC, and dialysate obtained from adult, remotely preconditioned rabbits). Remote
      preconditioning was induced by four 5-minute cycles of lower limb ischemia. Left
      ventricular (LV) function was assessed using a balloon-tipped catheter,
      glycolytic flux by tracer kinetics, and infarct size by tetrazolium staining.
      Isolated hearts underwent stabilization while perfused with standard Krebs
      Henseleit buffer (control and in vivo rIPC) or Krebs-Henseleit buffer with added
      dialysate, followed by global no-flow ischemia and reperfusion. RESULTS: Within
      the age groups, the baseline LV function was similar in all subgroups. In the
      adult rabbit hearts, rIPC and rIPC dialysate attenuated glycolytic flux and
      protected against ischemia-reperfusion injury, with better-preserved LV function
      compared with that of the controls. In contrast, in the neonatal hearts, the
      glycolytic flux was lower and LV function was better preserved in the controls
      than in the rIPC and dialysate groups. In the adult hearts, the infarct size was
      reduced in the rIPC and dialysate groups compared with that in the controls. In
      the neonatal hearts, the infarct size was smaller in the controls than in the
      rIPC and dialysate groups. CONCLUSIONS: Remote ischemic preconditioning does not
      protect against ischemia-reperfusion injury in isolated newborn rabbit hearts and
      might even cause deleterious effects. Similar adverse effects were induced by
      dialysate from remotely preconditioned adult rabbits.

PMID- 23871144
TI  - Effect of molecular chaperones on the expression of Candida antarctica lipase B
      in Pichia pastoris.
AB  - One of the reasons for limited heterologous protein secretion in Pichia pastoris
      is the suboptimal folding conditions inside the cell. The Hsp70 and Hsp40
      chaperone families in the cytoplasm or the ER regulate the folding and secretion
      of heterologous proteins. Here, we have studied the effect of chaperones Ydj1p,
      Ssa1p, Sec63p and Kar2p on the secretory expression of Candida antarctica lipase
      B (CalB) protein. Expression of CalB in P. pastoris resulted in the induction of
      Kar2p secretion into the medium surpassing the retrieval capacity of the cell.
      Individual overexpression of Ydj1p, Ssa1p and Sec63p in recombinant P. pastoris
      increased CalB expression level by 1.6-, 1.4- and 1.4-fold respectively compared
      to the control strain harboring only the CalB gene. However, overexpression of
      Kar2p had a negative effect on the expression of CalB. Moreover, Western blot
      analysis indicated accumulation and secretion of Kar2p in the ER, Golgi and
      extracellular medium in the chaperone coexpression strains. When expressed in
      combinations such as Ydj1p-Ssa1p, Ydj1p-Sec63p, Kar2p-Ssa1p, Kar2p-Sec63p, the
      expression level of CalB was increased by 2.5-, 1.5-, 1.5- and 1.5-fold
      respectively. Contrastingly, the Kar2p-Ydj1p combination resulted in decreased
      CalB secretion in the supernatant. From these results, we conclude that
      overexpression of Kar2p is not required for the secretion of CalB. Also, our work
      confirmed the synergistic effect of Ssa1p and Ydj1p chaperones in the expression
      of CalB.

PMID- 23871145
TI  - Isolation and characterization of plant growth promoting endophytic diazotrophic
      bacteria from Korean rice cultivars.
AB  - We have isolated 576 endophytic bacteria from the leaves, stems, and roots of 10
      rice cultivars and identified 12 of them as diazotrophic bacteria using a
      specific primer set of nif gene. Through 16S rDNA sequence analysis, nifH genes
      were confirmed in the two species of Penibacillus, three species of
      Microbacterium, three Bacillus species, and four species of Klebsiella. Rice
      seeds treated with these plant growth-promoting bacteria (PGPB) showed improved
      plant growth, increased height and dry weight and antagonistic effects against
      fungal pathogens. In addition, auxin and siderophore producing ability, and
      phosphate solubilizing activity were studied for the possible mechanisms of plant
      growth promotion. Among 12 isolates tested, 10 strains have shown higher auxin
      producing activity, 6 isolates were confirmed as strains with high siderophore
      producing activity while 4 isolates turned out to have high phosphate
      solubilizing activity. These results strongly suggest that the endophytic
      diazotrophic bacteria characterized in this study could be successfully used to
      promote plant growth and inducing fungal resistance in plants. 

PMID- 23871148
TI  - Observer-based reliable stabilization of uncertain linear systems subject to
      actuator faults, saturation, and bounded system disturbances.
AB  - A matrix inequality approach is proposed to reliably stabilize a class of
      uncertain linear systems subject to actuator faults, saturation, and bounded
      system disturbances. The system states are assumed immeasurable, and a classical
      observer is incorporated for observation to enable state-based feedback control.
      Both the stability and stabilization of the closed-loop system are discussed and
      the closed-loop domain of attraction is estimated by an ellipsoidal invariant
      set. The resultant stabilization conditions in the form of matrix inequalities
      enable simultaneous optimization of both the observer gain and the feedback
      controller gain, which is realized by converting the non-convex optimization
      problem to an unconstrained nonlinear programming problem. The effectiveness of
      proposed design techniques is demonstrated through a linearized model of F-18
      HARV around an operating point. 

PMID- 23871147
TI  - DNA-dependent SUMO modification of PARP-1.
AB  - Poly(ADP-ribose) polymerase 1 (PARP-1) plays an important role in DNA repair, but
      also contributes to other aspects of nucleic acid metabolism, such as
      transcriptional regulation. Modification of PARP-1 with the small ubiquitin
      related modifier (SUMO) affects its function as a transcriptional co-activator of
      hypoxia-responsive genes and promotes induction of the heat shock-induced HSP70.1
      promoter. We now report that PARP-1 sumoylation is strongly influenced by DNA.
      Consistent with a function in transcription, we show that sumoylation in vitro is
      enhanced by binding to intact, but not to damaged DNA, in a manner clearly
      distinct from the mechanism by which DNA damage stimulates PARP-1's catalytic
      activity. An enhanced affinity of PARP-1 for the SUMO-conjugating enzyme Ubc9
      upon binding to DNA is likely responsible for this effect. Sumoylation does not
      interfere with the catalytic or DNA-binding properties of PARP-1, and structural
      analysis reveals no significant impact of SUMO on the conformation of PARP-1's
      DNA-binding domain. In vivo, sumoylated PARP-1 is associated with chromatin, but
      the modification is not responsive to DNA damage and is not affected by PARP-1
      catalytic activity. Our results suggest that PARP-1's alternative modes of DNA
      recognition serve as a means to differentiate between distinct aspects of the
      enzyme's function. 

PMID- 23871149
TI  - Improved delay-dependent stability of neutral type neural networks with
      distributed delays.
AB  - This paper deals with the problem of improved delay-dependent stability analysis
      of neutral type neural networks with distributed delays. These conditions are in
      terms of linear matrix inequality (LMI), easily checked by recently developed
      algorithms in solving linear matrix inequalities (LMIs). Finally, numerical
      examples demonstrate effectiveness of the proposed method. 

PMID- 23871146
TI  - Preventing oxidation of cellular XRCC1 affects PARP-mediated DNA damage
      responses.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) binds intermediates of base excision
      repair (BER) and becomes activated for poly(ADP-ribose) (PAR) synthesis. PAR
      mediates recruitment and functions of the key BER factors XRCC1 and DNA
      polymerase beta (pol beta) that in turn regulate PAR. Yet, the molecular
      mechanism and implications of coordination between XRCC1 and pol beta in
      regulating the level of PAR are poorly understood. A complex of PARP-1, XRCC1 and
      pol beta is found in vivo, and it is known that pol beta and XRCC1 interact
      through a redox-sensitive binding interface in the N-terminal domain of XRCC1. We
      confirmed here that both oxidized and reduced forms of XRCC1 are present in mouse
      fibroblasts. To further understand the importance of the C12-C20 oxidized form of
      XRCC1 and the interaction with pol beta, we characterized cell lines representing
      stable transfectants in Xrcc1(-/-) mouse fibroblasts of wild-type XRCC1 and two
      mutants of XRCC1, a novel reduced form with the C12-C20 disulfide bond blocked
      (C12A) and a reference mutant that is unable to bind pol beta (V88R). XRCC1
      deficient mouse fibroblasts are extremely hypersensitive to methyl
      methanesulfonate (MMS), and transfected wild-type and C12A mutant XRCC1 proteins
      similarly reversed MMS hypersensitivity. However, after MMS exposure the cellular
      PAR level was found to increase to a much greater extent in cells expressing the
      C12A mutant than in cells expressing wild-type XRCC1. PARP inhibition resulted in
      very strong MMS sensitization in cells expressing wild-type XRCC1, but this
      sensitization was much less in cells expressing the C12A mutant. The results
      suggest a role for the oxidized form of XRCC1 in the interaction with pol beta in
      (1) controlling the PAR level after MMS exposure and (2) enabling the extreme
      cytotoxicity of PARP inhibition during the MMS DNA damage response. 

PMID- 23871150
TI  - Very-low speed control of PMSM based on EKF estimation with closed loop optimized
      parameters.
AB  - When calculating the speed from the position of permanent magnet synchronous
      motor (PMSM), the accuracy and real-time are limited by the precision of the
      sensor. This problem causes crawling and jitter at very-low speed. Using the
      angle from the position sensor, an extended Kalman filter (EKF) designed in dq
      coordinate is presented to solve this problem. The usage of position sensor
      simplifies the model and improves the accuracy of speed estimation. Specially, a
      closed loop optimal (CLO) method is devised to overcome the difficulty to adjust
      the parameters of the EKF. The EKF is the feedback link of speed control, CLO
      method is derived from the perspective of the speed step response to optimize the
      measurement covariance matrix and the system covariance matrix of EKF. Simulation
      and experimental results, comparing the low-speed performance of the EKF and
      sensor feedback methods, prove the effectiveness of the method to adjust the
      parameters of EKF and the advantages in eliminating the low speed jitter. 

PMID- 23871151
TI  - Empirical modeling of dynamic behaviors of pneumatic artificial muscle actuators.
AB  - Pneumatic Artificial Muscle (PAM) actuators yield muscle-like mechanical
      actuation with high force to weight ratio, soft and flexible structure, and
      adaptable compliance for rehabilitation and prosthetic appliances to the disabled
      as well as humanoid robots or machines. The present study is to develop empirical
      models of the PAM actuators, that is, a PAM coupled with pneumatic control
      valves, in order to describe their dynamic behaviors for practical control design
      and usage. Empirical modeling is an efficient approach to computer-based modeling
      with observations of real behaviors. Different characteristics of dynamic
      behaviors of each PAM actuator are due not only to the structures of the PAM
      actuators themselves, but also to the variations of their material properties in
      manufacturing processes. To overcome the difficulties, the proposed empirical
      models are experimentally derived from real physical behaviors of the PAM
      actuators, which are being implemented. In case studies, the simulated results
      with good agreement to experimental results, show that the proposed methodology
      can be applied to describe the dynamic behaviors of the real PAM actuators. 

PMID- 23871152
TI  - Does the choice of pre-registration paid employment impact on graduate nurse
      transition: an Australian study.
AB  - The process of transition for newly qualified registered nurses in their first
      year of practice remains a difficult and onerous proposition. Aside from well
      documented issues pertaining to orientation, preceptorship, appropriate patient
      allocation, indifferent communication and feedback from senior nursing staff,
      other influences can determine how new graduates adjust to the role of beginning
      registered nurse. The dataset from a large Australian study, that examined the
      impact of pre-registration paid employment on graduate nurse transition,
      contained a significant amount of data that indicated that undergraduate work
      choice might influence how senior colleagues view graduate nurses during their
      transition to registered nurse practice. Although this issue was beyond the scope
      of the original study, the volume of data and recurrence of this issue provided a
      strong rationale for further exploration. A secondary study was designed to
      explore the research question does previous undergraduate work choice influence
      how graduate nurses are viewed by senior colleagues during their transition to
      registered nurse? Using secondary analysis, and an interpretive descriptive
      approach, two qualitative data sets arising from focus groups and open ended
      questionnaire responses were analysed and three organising themes identified;
      drawing on prior learning, the burden of employment choice and outside the
      setting. The global theme "confidence and perceptions" describes graduate nurses'
      views about their prior paid employment choice being beneficial to them and
      perceived to assist them in the process of transition. Findings suggest that
      depending on the choice of prior paid employment, new graduates (particularly
      those who were formerly enrolled or second level nurses) are treated differently
      by their senior colleagues; in terms of the level of support offered in
      transition, whether prior skills and experiences from previous paid employment
      are acknowledged, made light of or dismissed. For successful transition to
      registered nurse practice it is recommended that senior nursing staff treat each
      new graduate equally, not based on prior paid employment experiences, and that
      all new graduates regardless of their prior work experiences require a period of
      adjustment to their new role. 

PMID- 23871153
TI  - Tumour antigen targeted monoclonal antibodies incorporating a novel
      multimerisation domain significantly enhance antibody dependent cellular
      cytotoxicity against colon cancer.
AB  - Tumour antigen targeted antibodies (mAbs) can induce natural killer (NK) cells to
      kill tumours through antibody dependent cellular cytotoxicity (ADCC) upon
      engagement of NK cell expressed FcgammaRIIIa. FcgammaRIIIa polymorphisms
      partially dictate the potency of the ADCC response. The high affinity
      FcgammaRIIIa-158-valine (V) polymorphism is associated with more potent ADCC
      response than the low affinity FcgammaRIIIa-158-phenylalanine (F) polymorphism.
      Because approximately 45% of patients are homozygous for the FcgammaRIIIa-158-F
      polymorphism (FF genotype), their ability to mount ADCC is impaired. We
      investigated whether a novel mAb capable of binding multiple antigen specific
      targets and engaging multiple low affinity FcgammaRIIIa receptors could further
      enhance ADCC against colon cancer in vitro. Specifically, we generated a novel
      anti-epidermal growth factor receptor (EGFR) antibody (termed a stradobody)
      consisting of an unmodified Fab sequence and two Immunoglobulin G, subclass 1
      (IgG1) Fc domains separated by an isoleucine zipper domain and the 12 amino-acid
      IgG2 hinge. The stradobody framework induced multimerisation and was associated
      with increased binding to the EGFR and FcgammaRIIIa. From a functional
      perspective, when compared to an unmodified anti-EGFR mAb with a sequence
      identical to cetuximab (a commercially available anti-EGFR mAb), stradobodies
      significantly enhanced ADCC. These effects were observed using both KRAS wild
      type HT29 and KRAS mutant SW480 colon cancer cells as targets, and by NK cells
      obtained from healthy donors and a cohort of patients with colon cancer. These
      data suggest that high avidity cross-linking of multiple tumour surface antigens
      and multiple NK cell associated FcgammaRIIIa molecules can enhance ADCC and
      partially overcome impaired ADCC by FF genotype individuals in vitro.

PMID- 23871154
TI  - Osteopoikilosis with involvement of the spine, an atypical presentation.

PMID- 23871155
TI  - National registry of patients with systemic lupus erythematosus of the Spanish
      Society of Rheumatology: objectives and methodology.
AB  - OBJECTIVE: To describe the objectives, design and methods of the Spanish Society
      of Rheumatology systemic lupus erythematosus (SLE) registry (RELESSER). METHODS:
      Multicenter, hospital-based registry, with retrospective collection of data from
      a large representative sample of adult patients with SLE (1997 ACR criteria)
      attending Spanish rheumatology services. The registry includes demographic data,
      frequent and infrequent (<1%) clinical manifestations, information about
      activity, damage, severity, comorbidity, treatments and mortality, collecting 359
      variables per patient, with highly standardized definitions. We performed a
      preliminary descriptive analysis of the data. RESULTS: Forty-five centers were
      involved and 4,024 SLE patients (91% with >= 4 ACR criteria) have been included;
      90% are women and 93% caucasians, with a median age at diagnosis of 33 years,
      median disease duration: 120 months, median follow-up duration: 104 months; 3,222
      (81%) of the patients are in active follow-up and 591 (14%) were lost to follow
      up. The median values of the SELENA-SLEDAI score, SLICC/ACR damage index and Katz
      severity index have been 2, 1 and 2, respectively. A total of 211 patients (6%)
      died. CONCLUSIONS: RELESSER represents the largest European SLE registry built to
      date, providing comprehensive and reliable information on SLE manifestations,
      disease status, comorbid conditions and treatments in daily clinical practice.
      RELESSER is constituted as a tool of great potential for multicenter clinical
      research in SLE.

PMID- 23871156
TI  - SER consensus statement on the use of biologic therapy for systemic lupus
      erythematosus.
AB  - OBJECTIVE: To provide a reference to rheumatologists and other physicians
      involved in the treatment of systemic lupus erythematosus (SLE) who are using, or
      about to use biologic therapies. METHODS: Recommendations were developed
      following a nominal group methodology and based on systematic reviews. The level
      of evidence and degree of recommendation were classified according to a model
      proposed by the Center for Evidence Based Medicine at Oxford. The level of
      agreement was established through a Delphi technique. RESULTS: We have produced
      recommendations on the use of belimumab, the only biological agent with approved
      indications for SLE, and other biological agents without an indication for SLE.
      The objective of treatment is to achieve a complete clinical response, taken as
      the absence of perceived or evident disease activity. Nuances regarding the use
      of biologic therapies in SLE were reviewed as well, such as the evaluation that
      should be performed prior to administration and the follow up of patients
      undergoing these therapies. CONCLUSIONS: We present the SER recommendations for
      the use of biological therapies in patients with SLE.

PMID- 23871157
TI  - Hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell
      transplantation in adult patients with idiopathic aplastic anemia.
AB  - We retrospectively investigated the incidence, risk factors, and outcomes of SOS
      (sinusoidal obstruction syndrome; previously veno-occlusive disease [VOD]) after
      allogeneic hematopoietic stem cell transplantation (alloHSCT) in aplastic anemia.
      Two hundred and sixty patients were included in the analysis. SOS developed in
      7.3% (n=19/260) of patients. Classical Cy (200 mg/m(2))-ATG was the most common
      conditioning regimen (84.2%) in the SOS group. The SOS mortality rate was 4/19
      (21.1%). Univariate analyses revealed that Cy 200 mg/m(2) conditioning (p=0.035),
      classical Cy-ATG conditioning (p=0.007), and horse ATG conditioning (p<0.001)
      were significant risk factors for developing SOS. Multivariate analysis revealed
      that only horse ATG conditioning was a poor prognostic factor (HR=3.484; 95% CI
      1.226-9.904; p=0.002). Rabbit ATG (HR 12.719; 95% CI 2.332-69.373; p=0.003) and
      weight gain>10% (HR 35.655; 95% CI 2.208-575.805; p=0.012) were risk factors in
      the overall SOS group. Both rabbit ATG conditioning and weight gain of more than
      10% were associated with poor overall survival with a median of 1.2 months (5Y
      survival rate, any risk factor vs. none: 74.6% vs. 0.0%; p<0.001; Fig. 2) in the
      SOS group. In conclusion, SOS is a relatively rare (7.3%) but highly fatal
      (21.1%) acute complication of alloHSCT in AA, and the horse ATG conditioning
      regimen was a significant risk factor for developing SOS.

PMID- 23871158
TI  - Leukemia associated mutant Wilms' tumor gene 1 protein promotes expansion of
      human hematopoietic progenitor cells.
AB  - The transcription factor Wilms' tumor gene 1 (WT1) is highly expressed in the
      majority of leukemias, suggesting a role in leukemogenesis. Acquired WT1
      mutations are reported as an independent predictor of poor clinical outcome, and
      mutations resulting in deletion of the entire DNA-binding zinc-finger domain
      (WT1delZ), is the most common type. The aim of this study was to study cellular
      effects of WT1(delZ) that may contribute to an oncogenic phenotype. We found that
      expression of WT1(delZ) supported proliferation of human hematopoietic CD34(+)
      progenitor cells. Moreover, WT1(delZ) transduced cells expressed erythroid
      markers, including raised levels of STAT5, independently of addition of
      erythropoietin. At the global gene expression level, WT1(delZ) caused
      upregulation of genes related to cell division and genes associated with
      erythroid maturation, in the absence of added erythropoietin. Our results
      indicate that WT1(delZ) promotes cell proliferation and expansion of progenitor
      cells, consistent with a possible role in leukemogenesis. 

PMID- 23871160
TI  - A rare case of renal cell carcinoma metastasis in the parotid gland eleven years
      after the initial diagnosis.

PMID- 23871159
TI  - Interleukin-6 and JAK2/STAT3 signaling mediate the reversion of dexamethasone
      resistance after dexamethasone withdrawal in 7TD1 multiple myeloma cells.
AB  - We previously reported the establishment and characteristics of a DXM-resistant
      cell line (7TD1-DXM) generated from the IL6-dependent mouse B cell hybridoma,
      7TD1 cell line. After withdrawing DXM from 7TD1-DXM cells over 90 days, DXM
      significantly inhibited the cell growth and induced apoptosis in the cells (7TD1
      WD) compared with 7TD1-DXM cells. Additionally, IL-6 reversed while IL-6 antibody
      and AG490 enhanced the effects of growth inhibition and apoptosis induced by DXM
      in 7TD1-WD cells. Our study demonstrates that 7TD1-DXM cells become resensitized
      to DXM after DXM withdrawal, and IL-6 and JAK2/STAT3 pathways may regulate the
      phenomenon. 

PMID- 23871161
TI  - Incidence of chemotherapy-induced amenorrhea in premenopausal women treated with
      adjuvant FOLFOX for colorectal cancer.
AB  - BACKGROUND: Studies indicate that the incidence of young women diagnosed with
      colorectal cancer is rising, thus there is an increasing number of female
      colorectal cancer survivors of premenopausal and child-bearing age. Adjuvant
      FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy is the most
      widely used standard treatment for stage III and high-risk stage II colon cancer.
      We evaluated the incidence of FOLFOX-induced amenorrhea in women age 50 and
      younger treated with adjuvant therapy for colorectal cancer. PATIENTS AND
      METHODS: A search of pharmacy records identified 119 women age 50 or younger who
      received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or
      III colorectal cancer from January 2002 and January 2011. Eligible patients were
      mailed an anonymous questionnaire. The returned surveys were reviewed and the
      results tallied. RESULTS: Seventy-three patients returned the questionnaire.
      Twenty-four patients were excluded from analysis: 19 were treated with pelvic
      radiotherapy, 2 patients had undergone bilateral oophorectomy, 2 had a
      hysterectomy, and 1 stopped menstruating before diagnosis. Forty-nine patient
      responses were analyzed. In total, 41% (n = 20) experienced amenorrhea during
      chemotherapy. Sixteen percent had persistent amenorrhea 1 year after completion
      of chemotherapy. The incidence of amenorrhea during chemotherapy trended higher
      in patients aged older than 40 compared with patients aged 40 and younger (59%
      vs. 31% [P = .075]). There was no statistically significant difference in
      persistent amenorrhea between the 2 age groups (24% vs. 13%; P = .42).
      CONCLUSION: In this retrospective series, there appears to be a trend toward
      FOLFOX induced amenorrhea during chemotherapy increasing with age. Twenty-four
      percent of women older than the age of 40 were found to have persistent
      amenorrhea after FOLFOX therapy. Because of the small sample size, the study is
      underpowered to detect a statistically significant difference between older and
      younger patients. Prospective studies are planned to further characterize the
      effect of FOLFOX on early menopause and fertility.

PMID- 23871162
TI  - Methylation of human papillomavirus-52 and -58 is a candidate biomarker in
      cervical neoplasia.
AB  - BACKGROUND: Previous studies of human papillomavirus (HPV)16/18 genome
      methylation have concluded that methylation status of the L1 gene might act as a
      biomarker for cervical intraepithelial neoplasia (CIN). OBJECTIVES: We
      investigated the correlation between methylation status in the L1 gene and the
      long control region (LCR) of HPV52/58 and CIN. STUDY DESIGN: Exfoliated cervical
      cells were taken from 54 HPV52-positive and 41 HPV58-positive women. The HPV
      genome was examined using bisulfite modification, polymerase chain reaction
      amplification, and sequencing. RESULTS: The CpGs were unmethylated or
      hypomethylated in the HPV52/58 LCR. In contrast, the methylation status of the
      HPV52 L1 gene was correlated with the severity of cervical neoplasia, with
      average percentages of 15%, 34%, and 52% for cervicitis/CIN1, CIN2, and CIN3,
      respectively (P<0.05). Methylation status of the HPV52 L1 gene was also
      correlated with the prognosis of CIN1/2, with median percentages of 15% and 35%
      for regression and persistence/progression, respectively (P<0.05). The
      methylation status of the HPV58 L1 gene was correlated with the severity of
      cervical neoplasia, with average percentages of 12%, 38%, and 61% for
      cervicitis/CIN1, CIN2, and CIN3, respectively (P<0.05). CONCLUSIONS: The
      increased methylation at the CpG sites in the HPV52/58 L1 gene was correlated
      with the severity of cervical neoplasia, similar to HPV16/18 in previous studies.
      These data suggest that HPV methylation status of the L1 gene is a candidate
      biomarker of CIN for detecting CIN2 and CIN3.

PMID- 23871164
TI  - Clinical and molecular epidemiological features of hemorrhagic fever with renal
      syndrome in Korea over a 10-year period.
AB  - BACKGROUND: Laboratory diagnosis of hemorrhagic fever with renal syndrome (HFRS),
      an infectious disease caused by rodent-borne hantaviruses in Asia and Europe,
      depends primarily on serological methods. Since the advent of such serodiagnostic
      tests, few reports are available about the clinical and molecular epidemiological
      features of HFRS. OBJECTIVES: To investigate the epidemioclinical features of
      HFRS patients treated at a tertiary-care teaching hospital in Seoul over a 10
      year period. STUDY DESIGN: Medical records of HFRS patients, admitted to a
      tertiary-care teaching hospital during February 2002 to February 2012, were
      reviewed. Sera from patients were tested for Hantaan virus (HTNV) and Seoul virus
      (SEOV) RNA using RT-PCR. RESULTS: Among 35 HFRS patients (mean age was 44.2+/
      14.7 years), 29 were male (82.9%). Acute renal failure developed in 27 patients
      (77.1%), and 12 patients (34.3%) were admitted to the intensive care unit (ICU).
      Conjunctival injection (OR 10.32, 95% CI 1.09-97.77, P=.04) and initial serum
      albumin less than 3g/dL (OR 22.83, 95% CI 1.45-359.93, P=.03) were risk factors
      for ICU admission. Of 35 acute-phase sera, 11 (31.4%) were positive for HTNV RNA.
      None were positive for SEOV RNA. CONCLUSIONS: HFRS was characterized by the
      clinical triad of fever, renal insufficiency and gastrointestinal symptoms.
      Conjunctival injection and serum albumin level were related to severity. A large
      scale multi-center study is needed to enhance insights into epidemioclinical
      characteristics of HFRS in Korea.

PMID- 23871163
TI  - Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African
      countries.
AB  - BACKGROUND: Hepatitis B virus (HBV) places a substantial health burden on Africa.
      Here, we investigated genetic diversity of HBV variants circulating in 4
      countries of sub-Saharan Africa using archived samples. In total, 1492 plasma
      samples were tested from HIV-infected individuals and pregnant women, among which
      143 (9.6%) were PCR-positive for HBV DNA (Cote d'Ivoire, 70/608 [11.5%]; Ghana,
      13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]). STUDY
      DESIGN/RESULTS: Phylogenetic analysis of the S-gene sequences identified HBV
      genotypes E (HBV/E, n=96) and A (HBV/A, n=47) distributed as follows: 87% of
      HBV/E and 13% of HBV/A in Cote d'Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and
      33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal
      nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively,
      suggesting a greater genetic diversity for this genotype than previously reported
      (p<0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and
      HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the
      only subgenotype of HBV/A found in Cameroon. In Cote d'Ivoire, HBV/A strains were
      classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic
      analysis of the sequences available from Africa supported earlier suggestions on
      the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa,
      respectively. Using predicted amino acid sequences, hepatitis B surface antigen
      (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68%
      of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg
      associated with immune escape. CONCLUSIONS: The observations of pan-African and
      global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and
      HBV/A3 almost exclusively in West and Central Africa suggest a more recent
      increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and
      HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the
      efficacy of prevention and control efforts in sub-Saharan Africa.

PMID- 23871165
TI  - Analysis of HHV-6 mutations in solid organ transplant recipients at the onset of
      cytomegalovirus disease and following treatment with intravenous ganciclovir or
      oral valganciclovir.
AB  - BACKGROUND: Human herpesvirus 6 (HHV-6) and human cytomegalovirus (HCMV) are
      major opportunistic pathogens in solid organ transplant (SOT) recipients. The use
      of antivirals for the treatment of HCMV disease can result in the development of
      drug resistance mutations in HCMV and also potentially in HHV-6. OBJECTIVES: The
      emergence of HHV-6 drug resistance mutations was evaluated in SOT recipients at
      the onset of HCMV disease and following treatment with ganciclovir (GCV) or
      valganciclovir (VGCV). STUDY DESIGN: Detection of HHV-6 was performed by real
      time PCR from whole blood samples serially obtained from SOT recipients treated
      for HCMV disease with an induction dose of intravenous GCV or oral VGCV for 21
      days followed by VGCV maintenance for 28 days in both arms. Baseline and last
      positive HHV-6 samples were tested for mutations in the genes encoding the
      protein kinase (U69) and the DNA polymerase (U38). RESULTS: The rate of HHV-6
      viraemia among SOT patients with HCMV disease at baseline was 3.2% (5/155). All
      isolates belonged to the HHV-6B species. Mutations L213I and Y479H were detected
      at baseline and at later times in the U69 kinase. Mutation L213I was previously
      reported as polymorphism whereas the role of mutation Y479H in drug resistance is
      unknown. Mutations D854E and E855Q found in the DNA polymerase were known as
      natural variants. CONCLUSIONS: The incidence of HHV-6 viraemia in SOT recipients
      with established HCMV disease before initiation of antiviral therapy was low.
      Treatment with GCV or VGCV did not induce the emergence of HHV-6 drug resistance
      mutations.

PMID- 23871166
TI  - Evaluation of laboratory tests for dengue diagnosis in clinical specimens from
      consecutive patients with suspected dengue in Belo Horizonte, Brazil.
AB  - BACKGROUND: Dengue is a widely spread arboviral disease in tropical and
      subtropical regions of the world. Dengue fever presents clinical characteristics
      similar to other febrile illness. Thus laboratory diagnosis is important for
      adequate management of the disease. OBJECTIVES: The present study was designed to
      evaluate the diagnostic performance of real-time PCR and serological methods for
      dengue in a real epidemic context. STUDY DESIGN: Clinical data and blood samples
      were collected from consecutive patients with suspected dengue who attended a
      primary health care unit in Belo Horizonte, Brazil. Serologic methods and real
      time PCR were performed in serum samples to confirm dengue diagnosis. RESULTS:
      Among the 181 consecutive patients enrolled in this study with suspected dengue,
      146 were considered positive by serological criteria (positive NS1 ELISA and/or
      anti-dengue IgM ELISA) and 138 were positive by real-time PCR. Clinical criteria
      were not sufficient for distinguishing between dengue and non-dengue febrile
      illness. The PCR reaction was pre-optimized using samples from patients with
      known viral infection. It had similar sensitivity compared to NS1 ELISA (88% and
      89%, respectively). We also evaluated three commercial lateral flow
      immunochromatographic tests for NS1 detection (BIOEASY, BIORAD and PANBIO). All
      three tests showed high sensitivity (94%, 91% and 81%, respectively) for dengue
      diagnosis. CONCLUSION: According to our results it can be suggested that lateral
      flow tests for NS1 detection are the most feasible methods for early diagnosis of
      dengue.

PMID- 23871167
TI  - EEG-fMRI in focal epilepsy: local activation and regional networks.
AB  - OBJECTIVE: To identify features of BOLD signal change associated with interictal
      epileptiform discharges (IEDs) in a heterogeneous group of focal epilepsy
      patients. METHODS: EEG/fMRI studies in 27 focal epilepsy patients were reviewed
      with attention given to the extent and location of the IED and the resulting
      pattern of BOLD signal change. Second order group analysis was used to identify
      common features. RESULTS: fMRI results provided novel clinical information for
      individual patients. We identified a significant common node within the
      ipsilateral piriform cortex as well as patterns involving distant cortical or
      subcortical areas. CONCLUSION: Despite the heterogeneity of IEDs in focal
      epilepsy, there are important common features underpining IEDs with a highly
      significant fMRI node in the ipsilateral piriform cortex. SIGNIFICANCE: There are
      important common features in the networks involved in IEDs in patients with a
      heterogeneous range of epileptogenic foci. We confirm that the piriform cortex is
      a common node underlying IEDs in patients with focal epilepsy and so provides a
      target for further study and potential therapy. We describe important features of
      BOLD signal change that accompany focal and diffuse IEDs that will help
      researchers and clinicians navigate the sometimes complex findings revealed by
      these studies.

PMID- 23871168
TI  - History of trauma and the association with baseline symptoms in an Ultra-High
      Risk for psychosis cohort.
AB  - Few studies have addressed the correlates of trauma in young people at Ultra-High
      Risk (UHR) of developing a psychotic disorder. We aimed to examine baseline
      differences in intensity, form and content of attenuated positive psychotic
      symptoms, other clinical symptomatology and comorbidity between UHR patients with
      and without a history of trauma. In a sample of 127 UHR individuals (53 male, 74
      female; mean age 18.2 years, range 14-26) we assessed trauma history and baseline
      symptomatology using an audit tool developed to retrieve data from patient
      medical records. 56% of the subjects had experienced at least one type of trauma.
      The intensity of perceptual abnormalities was significantly higher in the group
      with a history of physical abuse and 'other trauma' compared to those without a
      trauma history. Physical abuse was related to higher levels of visual
      disturbances, suspiciousness, grandiose beliefs and low mood compared to those
      without a history of physical abuse. Sexual trauma was related to perceptual
      disturbances with abusive content and PTSD symptoms. The prevalence of previous
      trauma in people at UHR of developing psychosis is high. Our findings tentatively
      suggest that different types of trauma may impact differently on initial
      presentation to UHR services. 

PMID- 23871169
TI  - Moving beyond transition outcomes: meta-analysis of remission rates in
      individuals at high clinical risk for psychosis.
AB  - Recent evidence suggests that transition risks from initial clinical high risk
      (CHR) status to psychosis are decreasing. The role played by remission in this
      context is mostly unknown. The present study addresses this issue by means of a
      meta-analysis including eight relevant studies published up to January 2012 that
      reported remission rates from an initial CHR status. The primary effect size
      measure was the longitudinal proportion of remissions compared to non-remission
      in subjects with a baseline CHR state. Random effect models were employed to
      address the high heterogeneity across studies included. To assess the robustness
      of the results, we performed sensitivity analyses by sequentially removing each
      study and rerunning the analysis. Of 773 subjects who met initial CHR criteria,
      73% did not convert to psychosis along a 2-year follow. Of these, about 46% fully
      remitted from the baseline attenuated psychotic symptoms, as evaluated on the
      psychometric measures usually employed by prodromal services. The corresponding
      clinical remission was estimated as high as 35% of the baseline CHR sample. The
      CHR state is associated with a significant proportion of remitting subjects that
      can be accounted by the effective treatments received, a lead time bias, a
      dilution effect, a comorbid effect of other psychiatric diagnoses. 

PMID- 23871171
TI  - Physicians, Internet and the vox populi.

PMID- 23871172
TI  - A useful surgical technique for retrieval of a broken guide pin in the midfoot.
AB  - Perioperative instrument breakage is not an infrequent occurrence, even for
      experienced surgeons. The most commonly reported instrument breaks in orthopedic
      procedures are drill bits, followed by Kirschner wires and cannulated guide pins.
      The reasons for failure include improper technique and repetitive use. The
      retrieval of broken hardware can be technically challenging, particularly if the
      fragment has become embedded in bone. Retrieval methods have been described for
      cannulated guide pin fragments in the hip; however, no specific techniques have
      been described for the retrieval of guide pin fragments embedded in the bones of
      the foot. In the present report, we describe a technique we have found useful for
      retrieval of a guide pin fragment that had broken off during a Lisfranc fracture
      repair 6 weeks earlier. The technique was used in a delayed situation; however,
      we believe it would be even easier to use during an intraoperative breakage. 

PMID- 23871173
TI  - Electronic health records, privacy, and surveillance.

PMID- 23871174
TI  - Metastatic calcaneal lesion associated with uterine carcinosarcoma.
AB  - Metastatic lesions of uterine carcinosarcoma most commonly occur in the abdomen
      and lungs and less frequently in highly vascularized bone. We report a rare case
      of an 86-year-old female with uterine carcinosarcoma with metastasis to the left
      calcaneus. The patient had a history of uterine carcinosarcoma with hysterectomy
      and bilateral salpingo-oophorectomy, along with bilateral pelvic and aortic
      lymphadenectomy, with no adjuvant therapy. The initial pedal complaint was that
      of left foot pain. The initial radiographic findings were negative; however,
      magnetic resonance imaging scans revealed a substantial area of marrow edema in
      the calcaneus. An excisional biopsy was performed, and histopathologic analysis
      revealed adenocarcinoma with features consistent with the patient's previous
      uterine tumor specimen. The patient was given one treatment of chemotherapy and
      was discharged to a hospice, where she died of her disease 2 weeks later. 

PMID- 23871175
TI  - Pinning across the metatarsophalangeal joint for hammertoe correction: where are
      we aiming and what is the damage to the metatarsal articular surface?
AB  - Kirschner wire (K-wire) fixation across the metatarsophalangeal joint (MTPJ) is
      commonly used in hammertoe repair surgery. The purpose of the present study was
      twofold: (1) to determine where the K-wire penetrates the metatarsal articular
      surface to achieve a rectus digit; and (2) to quantify the percentage of
      cartilage disruption to better understand the consequences of K-wire
      transfixation of the MTPJ. Arthrodesis was conducted on the second, third, and
      fourth proximal interphalangeal joints of 10 below-the-knee cadaver specimens,
      using a 1.6-mm K-wire. Digital alignment was confirmed with simulated
      weightbearing intraoperatively and radiographically. The K-wire was removed, and
      the MTPJ was dissected until the metatarsal head was fully exposed. The
      penetration point was plotted on a quadrant system with deviation noted from the
      epicenter. Center was defined as the point equidistant from the medial-to-lateral
      and superior-to-inferior edges on the distal surface of the metatarsal head,
      excluding the plantar condyles. Statistically significantly deviations were found
      in the K-wire placement from the center (35.9% +/- 17.5%, p < .001), medial-to
      lateral width (22.2% +/- 19.2%, p < .001), and dorsal-to-plantar height (15.8% +/
      25.0%, p = .002). Relative to the center, the K-wire was superior in 22 (79%),
      inferior in 6 (21%), medial in 22 (79%), and lateral in 6 (21%) of the cadaveric
      MTPJs. The mean percentage of disruption of the articular cartilage was 1.8% +/-
      .4% and was similar for the second, third, and fourth MTPJs (p = .13) and for the
      left and right feet (p = .75). This information could be used to guide surgeons
      when they transfixate the MTPJ during hammertoe correction and might contribute
      to preservation of the articular cartilage. 

PMID- 23871176
TI  - [Single-incision cholecystectomy: a safe innovation?].

PMID- 23871177
TI  - [Neuroendocrine carcinoma of the digestive tract: a literature review].
AB  - Neuroendocrine carcinoma is a rare and agressive malignant tumor, mainly
      developing at the expense of the respiratory and of the digestive tract. Among
      the digestive tract, appendix, small bowel, and pancreas are the preferential
      sites of involvement, other locations have been more rarely reported.
      Neuroendocrine digestive tumors may present with various symptoms in relationship
      with their localization and a complex pathophysiology. Diagnosis is often made at
      an advanced stage, explaining partly the bad prognosis of these tumors. The
      optimal management of digestive neuroendocrine tumors is rendered difficult by
      their rarity and by a low number of randomized trials. We review the literature
      regarding epidemiologic and prognostic features of these rare tumors, their
      diagnostic and therapeutic care. Potential complications are also discussed. 

PMID- 23871178
TI  - Effects of EEG-vigilance regulation patterns on early perceptual processes in
      human visual cortex.
AB  - OBJECTIVE: To investigate influences of EEG-vigilance regulation patterns on
      perceptual processing during sustained visual attention in early visual areas.
      METHODS: We compared a subject group with stable vigilance regulation to a group
      with unstable EEG-vigilance regulation. A rapid serial visual presentation stream
      (RSVP) elicited a 7.5 Hz steady state visual evoked potential (SSVEP), a
      continuous sinusoidal brain response as a measure of attentional resource
      allocation during sustained attention in early visual cortex. Subjects performed
      a target discrimination task. 150 trials were divided into two parts (75 trials
      each, trial duration: 11 s). RESULTS: A significant interaction vigilance group
      by experimental part provided significantly greater SSVEP amplitudes for the
      unstable group in the second compared to the first part of the experiment. Both
      groups showed training effects with increased hit rates and d'-values in the
      second part of the experiment. CONCLUSIONS: The unexpected finding of SSVEP
      amplitude increase for the unstable group might be due to competitive
      interactions for neural resources between the alpha response and SSVEPs.
      SIGNIFICANCE: Individual patterns of EEG-vigilance regulation have a moderate
      impact on early sensory processing during sustained visual attention that is not
      paralleled in task performance.

PMID- 23871179
TI  - Novel EEG pattern associated with impaired cerebrovascular reserve in Moyamoya
      disease.

PMID- 23871180
TI  - Complex cognitive functions underlie aesthetic emotions: comment on "From
      everyday emotions to aesthetic emotions: towards a unified theory of musical
      emotions" by Patrik N. Juslin.

PMID- 23871181
TI  - Comment on Review article by Patrik Juslin: "From everyday emotions to aesthetic
      emotions: Towards a unified theory of musical emotions".

PMID- 23871182
TI  - Experience of combined liver-kidney transplantation for acute-on-chronic liver
      failure patients with renal dysfunction.
AB  - BACKGROUND: The aim of this study was to evaluate the outcomes of orthotopic
      liver transplantation (OLT) or combined liver-kidney transplantation (CLKT) for
      acute-on-chronic liver failure (ACLF) patients with renal dysfunction. METHODS:
      From January 2001 to December 2009, 133 patients underwent OLT for ACLF at our
      center. Among them, 30 had both ACLF and renal dysfunction. Of the 30 patients,
      12 underwent CLKT for end-stage renal disease (ESRD), and the other 18 with
      hepatorenal syndrome type 1 (HRS1) underwent OLT alone. ACLF was defined
      according to the Asian Pacific Association for the Study of Liver Consensus
      Meeting. Clinical data were reviewed for survival outcomes. RESULTS: The median
      model for end-stage liver disease score (MELD) of patients with ACLF was 28.
      Among the 133 patients, all of whom received deceased donor liver grafts, 12 also
      got the kidney grafts from the same deceased donor. The hospital mortality rate
      was 21.8% for all patients with ACLF. The 5-year survival rates were 72.8% for
      patients without renal dysfunction and 70% for patients with renal dysfunction.
      The results of patients with ESRD who underwent CLKT were better than those of
      subjects without renal dysfunction or patients with HRS1 who underwent OLT alone.
      CONCLUSIONS: OLT alone improved renal function in most patients with HRS1,
      including those requiring short-term hemodialysis. Simultaneous liver-kidney
      transplantation was an excellent strategy for patients with both ACLF and ESRD.
      It provided protection to the kidney allograft for liver-based metabolic diseases
      affecting the kidney. The rate of acute rejection episodes in kidneys was low.

PMID- 23871183
TI  - Ultrasonographic optic nerve sheath diameter is correlated with arterial carbon
      dioxide concentration during reperfusion in liver transplant recipients.
AB  - BACKGROUND: Cerebral blood flow and intracranial pressure (ICP) has been known to
      be increased after graft reperfusion during liver transplantation, which was
      correlated with arterial carbon dioxide concentration (PaCO2). Ultrasonographic
      measurement of optic nerve sheath diameter (ONSD) is a simple and noninvasive
      method for evaluating ICP. We investigated the correlation between ONSD and the
      PaCO2 during reperfusion in liver transplant recipients. METHODS: Twenty liver
      transplant recipients with end-stage liver disease were enrolled. We measured
      ONSD and PaCO2 at 6 time points: preinduction, preanhepatic phase, anhepatic
      phase, 5 minutes after reperfusion, 30 minutes after reperfusion, and neohepatic
      phase. Pearson correlation analysis and receiver operating characteristics (ROC)
      curve analysis were performed. RESULTS: ONSD measured 5 minutes after reperfusion
      was significantly higher compared with the other time points. Differences in ONSD
      between the anhepatic phase and 5 minutes after reperfusion demonstrated
      significant correlations with both PaCO2 at the anhepatic phase and 5 minutes
      after reperfusion (both P < .001). On the ROC curve analysis, PaCO2 of 35 mm Hg
      at the anhepatic phase could be used to indicate >=20% changes in ONSD after
      reperfusion. There were significant increases in ONSD after graft reperfusion in
      liver transplant recipients with PaCO2 >= 35 mm Hg at the anhepatic phase (P =
      .004). CONCLUSION: ONSD was increased just after reperfusion, which demonstrated
      good correlation with PaCO2 during reperfusion in liver transplant recipients.
      This finding suggests that the carbon dioxide can play a key role in increasing
      ONSD during hepatic graft reperfusion.

PMID- 23871184
TI  - Effect of prostaglandin E-1 on Wisconsin University and histidine-tryptophan
      ketoglutarate preservation solutions on preservation injury of the perfused
      liver.
AB  - BACKGROUND: The aim of this study was to investigate the effects of prostaglandin
      E-1 (PGE-1) on preservation injury in livers perfused with the University of
      Wisconsin (UW) or histidine-tryptophan-ketoglutarate (HTK) solutions. MATERIALS
      AND METHODS: Five groups each including six rats included. Ringer's lactate RL
      (group 1), HTK (group 2), HTK + PGE-1 (group 3), UW (group 4), or UW PGE-1 (group
      5). Liver tissue and preservation fluid samples were obtained from the perfused
      lives for pathological and biochemical examinations respectively at 0, 6 and 12
      hours. RESULTS: Upon biochemical examination, aspartate aminotrasnferase and
      alanine aminotransferase values were highest among the group with RL solution and
      lowest with PGE-1. Liver structure was found to be damaged immediately after RL
      solution, whereas it was preserved in the other four groups. Fewer cellular
      changes were reported at the end of 12 hours in the groups administered PGE-1
      compared with the other groups. CONCLUSIONS: PGE-1 when applied before
      preservation protected liver functions, decreased pathologic injury, and delayed
      changes that occur under cold ischemic conditions.

PMID- 23871185
TI  - Fenton treatment of landfill leachate under different COD loading factors.
AB  - The application of Fenton treatment technology for treatment of landfill leachate
      greatly depends on the optimum Fenton operating conditions for a specific
      leachate. Determining optimum Fenton conditions requires multiple experiments
      using variable reaction parameters (pH, temperature, and H2O2 and Fe(2+) doses)
      and previous researches show a wide range of optimal operating conditions. In
      this study, the applicability of the dimensionless loading factor (LCOD), which
      is defined as the initial COD (COD0) of leachate with respect to available O2 for
      oxidation, was examined to derive optimum Fenton oxidant dose using reduced set
      of experiments. The Fenton experiments were conducted using leachates with three
      different COD0 concentrations, 1092, 546, and 273mgL(-1), LCOD in the range of
      0.25-1.0, and H2O2/Fe(2+) 1.8 (w/w). The experimental data were analyzed to
      determine the correlation between the LCOD factor and selected feasibility
      parameters, amongst which were: (i) the COD removal kinetics, (ii) the total COD
      removal, (iii) the usability of H2O2 with respect to COD removal, (iv) leachate
      biodegradability, and (v) treatment cost incurred by chemical usage. The
      experimental COD removal with respect to the amount of O2 supplied by H2O2 was
      compared with respect to the optimum COD removal efficiency by the equation:
      eta(FP(optimum)=0.733L(COD)-0.182 as developed by Singh and Tang (2013) and a
      LCOD of 0.75 was determined to be the optimum L(COD) for leachate treatment.

PMID- 23871186
TI  - Impact of source segregation intensity of solid waste on fuel consumption and
      collection costs.
AB  - Fuel consumption and collection costs of solid waste were evaluated by the aid of
      a simulation model for a given collection area of a medium-sized Italian city.
      Using the model it is possible to calculate time, collected waste and fuel
      consumption for a given waste collection route. Starting from the data for the
      current waste collection scenario with a Source Segregated (SS) intensity of 25%,
      all the main model error evaluated was ?1.2. SS intensity scenarios of 25%, 30%,
      35% and 52% were simulated. Results showed an increase in the average fuel
      consumed by the collection vehicles that went from about 3.3L/tonne for 25% SS
      intensity to about 3.8L/tonne for a SS intensity of 52%. Direct collection costs,
      including crews and vehicle purchase, ranged from about 40?/tonne to about
      70?/tonne, respectively, for 25% and 52% SS intensity. The increase in fuel
      consumption and collection costs depends on the density of the waste collected,
      on the collection vehicle compaction ratio and on the waste collection vehicle
      utilization factor (WCVUF). In particular a reduction of about 50% of the WCVUF
      can lead to an average increase of about 80% in fuel consumption and 100% in
      collection costs. 

PMID- 23871187
TI  - Bob Ham (1937-2012): a pioneer in waste management.

PMID- 23871188
TI  - Review and prospect of emerging contaminants in waste--key issues and challenges
      linked to their presence in waste treatment schemes: general aspects and focus on
      nanoparticles.
AB  - The presence in waste of emerging pollutants (EPs), whose behaviours and effects
      are not well understood, may present unexpected health and environmental risks
      and risks for the treatment processes themselves. EP may include substances that
      are newly detected in the environment, substances already identified as risky and
      whose use in items is prohibited (but which may be present in old or imported
      product waste) or substances already known but whose recent use in products can
      cause problems during their future treatment as waste. Several scientific studies
      have been conducted to assess the presence of EP in waste, but they are mostly
      dedicated to a single category of substance or one particular waste treatment. In
      the absence of a comprehensive review focused on the impact of the presence of EP
      on waste treatment schemes, the authors present a review of the key issues
      associated with the treatment of waste containing emerging pollutants. This
      review presents the typologies of emerging pollutants that are potentially
      present in waste along with the major challenges for each treatment scheme
      (recycling, composting, digestion, incineration, landfilling and wastewater
      treatment). All conventional treatment processes are affected by these new
      pollutants, and they were almost never originally designed to consider these
      substances. In addition to these general aspects, a comprehensive review of
      available data, projects and future R&D needs related to the impact of
      nanoparticles on waste treatment is presented as a case study. 

PMID- 23871189
TI  - Fragmentation of salivary stones with a 980nm diode laser.
AB  - OBJECTIVE: Intraductal laser lithotripsy is a preferred method to fragment large,
      immobile intraglandular salivary stones. A number of different laser systems has
      been investigated for this purpose. It was our aim to study the effectiveness of
      a 980nm diode laser when fragmenting salivary stones in an experimental set up.
      METHODS: In an experimental set up we used a 980nm diode laser for the
      lithotripsy of 9 salivary stones. The temperature circle around the laser fibre
      tip was measured and stone remnants were chemically analysed for their
      composition. RESULTS: The salivary stones had a mean diameter of
      6.7mm*5.6mm*3.0mm. Laser fragmentation with the diode laser was successful at all
      stones. The temperature next to the salivary stone increased to around 30 degrees
      C during the active lithotripsy with continuous rinsing (fluid temperature 21
      degrees C). At a distance of 2mm the temperature around the laser fibre's tip is
      reduced by already about 50%. The salivary stones mainly consisted of carbonate
      apatite, followed by beta-calcium phosphate and other calcium phosphates.
      CONCLUSION: The fragmentation of salivary stones with a 980nm diode laser is
      possible in principle. Under a continuous irrigation with a positioning of the
      laser fibre's tip at the centre of the stone, no relevant temperature increase in
      the vicinity of the stone occurs. However, before the laser is used in humans, in
      vivo experiments on animal material seem to be advisable.

PMID- 23871190
TI  - Synchronous bilateral tonsillar carcinomas associated with human papillomavirus.
AB  - Although the incidence of human papillomavirus (HPV)-positive oropharyngeal
      carcinoma is increasing, only a limited number of synchronous bilateral HPV
      positive tonsillar carcinomas have been reported to date. Here, we describe an
      additional case of 61-year-old female. Pathological analysis proved squamous cell
      carcinoma in biopsy specimens from bilateral tonsillar lesions and a fine needle
      aspirate from an enlarged cervical node. Polymerase chain reaction (PCR) and
      direct sequencing showed HPV-16 DNA in all of the biopsy specimens and fine
      needle aspirate with completely concordant sequences. Bilateral tonsillar lesions
      were immunohistochemically positive for p16. Taken together with radiological
      findings, she was diagnosed to have bilateral tonsillar carcinomas (cT1N2bM0 on
      the right side and cT2N0M0 on the left side). We administered concurrent
      chemoradiotherapy to treat these synchronous lesions, and the restaging workup
      resulted in overall complete response. No recurrent and/or metastatic disease has
      been evident 20 months after the restaging. It seems reasonable to include
      bilateral tonsils as a therapeutic target in the treatment of HPV-positive
      unknown primary carcinoma. 

PMID- 23871191
TI  - Nutritional risk screening and its clinical significance in hospitalized
      children.
AB  - BACKGROUND & AIMS: To analyse nutritional risk in hospitalized children and its
      relationship with clinical outcomes to provide evidence for improved nutritional
      management. METHODS: The investigation involved 1325 consecutively enrolled
      hospitalized children from Nanjing Children's Hospital. The nutritional risks in
      the hospitalized children were evaluated using the STRONGkids tool. During
      hospitalization, the incidence of infectious complications, length of hospital
      stay, weight loss, hospital expenses and nutritional support were recorded.
      RESULTS: The percentages of children with high, moderate and low nutritional risk
      were 9.1% (121), 43.3% (574) and 47.6% (630), respectively. Children with
      cardiac, respiratory or oncologic disease were most likely to have high
      nutritional risk. STRONGkids scores were correlated with clinical outcome. Higher
      complication rates, longer stay lengths, greater weight loss and greater hospital
      expenses were observed in children with high nutritional risk compared to those
      with moderate or low risk (p < 0.001). Nutritional support during hospitalization
      was given to 62.8% (76) of children with high nutritional risk, 18.6% (107) of
      children with moderate nutritional risk and 8.9% (56) of children with low
      nutritional risk. CONCLUSIONS: Hospitalized children exposed to high or moderate
      nutritional risks have poor clinical outcomes. Nutritional support is not yet
      performed appropriately. Evidence-based guidelines should be created to improve
      this situation.

PMID- 23871192
TI  - Accuracy of quantitative magnetic resonance and eight-electrode bioelectrical
      impedance analysis in normal weight and obese women.
AB  - BACKGROUND & AIMS: Quantitative magnetic resonance (QMR) has previously been
      shown to both overestimate and underestimate average fat mass (FM) in humans.
      Eight-electrode bioelectrical impedance analysis (BIA) has previously been found
      biased as well as successfully validated. We report cross-sectional accuracy of
      QMR and eight-electrode BIA evaluated with air displacement plethysmography (ADP)
      as reference method. METHODS: Fat mass and fat free mass (FFM) by QMR and eight
      electrode BIA were evaluated against ADP as reference in 38 normal weight and 30
      obese women. Total body water estimates by QMR and eight-electrode BIA were
      compared. RESULTS: Fat mass was overestimated by QMR (1 +/- 2 kg, p < 0.001) and
      was underestimated by eight-electrode BIA (1 +/- 3 kg, p = 0.03, Bonferroni
      adjusted p = 0.29) in normal weight women. Fat mass was underestimated by both
      QMR (2 +/- 2 kg, p < 0.001) and eight-electrode BIA (9 +/- 3 kg, p < 0.001) in
      obese women. Fat free mass biases were of similar magnitude but in opposite
      direction to FM biases. Total body water estimates were larger by eight-electrode
      BIA compared to QMR (1-10 kg). CONCLUSIONS: Fat mass and FFM by QMR were both
      biased but in opposite directions in both normal weight and obese women. Eight
      electrode BIA FM and FFM estimates were imprecise and biased in obese women.
      Thus, QMR is more precise and more accurate than eight-electrode BIA for
      estimating body composition in women, but is not accurate enough to be used for
      individual single assessment of body composition.

PMID- 23871193
TI  - Comprehensive classification of fragility fractures of the pelvic ring:
      Recommendations for surgical treatment.
AB  - Due to the increasing life expectancy, orthopaedic surgeons are more and more
      often confronted with fragility fractures of the pelvis (FFPs). These kinds of
      fractures are the result of a low-energy impact or they may even occur
      spontaneously in patients with severe osteoporosis. Due to some distinct
      differences, the established classifications for pelvic ring lesions in younger
      adults do not fully reflect the clinical and morphological criteria of FFPs. Most
      FFPs are minimally displaced and do not require surgical therapy. However, in
      some patients, an insidious progress of bone damage leads to increasing
      displacement, nonunion and persisting instability. Therefore, new concepts for
      surgical treatment have to be developed to address the functional needs of the
      elderly patients. Based on an analysis of 245 consecutive patients with FFPs, we
      propose a novel classification system for this condition. This classification is
      based on morphological criteria and it corresponds with the degree of
      instability. Also in the elderly, these criteria are the most important for the
      decision on the type of treatment as well as type and extent of surgery. The
      estimation of the degree of instability is based on radiological and clinical
      findings. The classification gives also hints for treatment strategies, which may
      vary between minimally invasive techniques and complex surgical reconstructions. 

PMID- 23871194
TI  - Effects of thermal treatment on chemical, mechanical and colour traits in Norway
      spruce wood.
AB  - In several different branches of the wood industry heat treatment is a growing
      application as it changes the chemical, mechanical, physical and biological
      properties of wood. Investigations using wet chemical analyses, Fourier transform
      infrared spectroscopy, size exclusion chromatography, and CIELab colour system
      have been conducted to study the changes in Norway spruce wood subjected to
      temperature up to 270 degrees C over a 30 min time period. The results showed
      that mass loss (ML), total crystallinity index (TCI) of cellulose, total colour
      difference (DeltaE*), and the content of lignin and extractives increased with
      the temperature, whereas degree of polymerization (DP) of cellulose, modulus of
      rupture (MOR), modulus of elasticity (MOE), lightness difference (DeltaL*), and
      the content of holocellulose, cellulose and hemicelluloses all decreased with the
      thermal treatment. Relationships between temperature and the examined wood traits
      were all fitted by exponential curves. Power law relationships were found to fit
      the trends for DP of cellulose with DeltaE*, DeltaL*, and TCI of cellulose. Also
      found were power law regressions for the content of hemicelluloses with MOE, MOR,
      DeltaL*, and ML. Temperatures ranging from 20 to 187 degrees C formed a compact
      cluster, clearly separated from the higher examined temperatures in the
      multivariate wood trait space.

PMID- 23871195
TI  - Thinking meta-theoretically about the role of internalization in the development
      of body dissatisfaction and body change behaviors.
AB  - Internalization of societal standards of physical attractiveness (i.e.,
      internalization of the thin ideal for women and internalization of the
      mesomorphic ideal for men) is a widely studied and robust risk factor for body
      dissatisfaction and maladaptive body change behaviors. Substantial empirical
      research supports internalization as both a mediator and a moderator of the
      relation between societal influences and body dissatisfaction. In this paper, a
      primer on mediation and moderation is followed by a review of literature and
      discussion of the extent to which internalization can theoretically fulfill the
      roles of both mediation and moderation. The literature review revealed a stark
      contrast in research design (experimental versus non-experimental design) when
      alternate conceptualizations of internalization are adopted. A meta-theoretical,
      moderated mediation model is presented. This model integrates previous research
      and can inform future empirical and clinical endeavors. 

PMID- 23871196
TI  - Respiratory-induced prostate motion using wavelet decomposition of the real-time
      electromagnetic tracking signal.
AB  - PURPOSE: The objective of this work is to characterize and quantify the impact of
      respiratory-induced prostate motion. METHODS AND MATERIALS: Real-time
      intrafraction motion is observed with the Calypso 4-dimensional nonradioactive
      electromagnetic tracking system (Calypso Medical Technologies, Inc. Seattle,
      Washington). We report the results from a total of 1024 fractions from 31
      prostate cancer patients. Wavelet transform was used to decompose the signal to
      extract and isolate the respiratory-induced prostate motion from the total
      prostate displacement. RESULTS: Our results show that the average respiratory
      motion larger than 0.5 mm can be observed in 68% of the fractions. Fewer than 1%
      of the patients showed average respiratory motion of less than 0.2 mm, whereas
      99% of the patients showed average respiratory-induced motion ranging between 0.2
      and 2 mm. The maximum respiratory range of motion of 3 mm or greater was seen in
      only 25% of the fractions. In addition, about 2% patients showed anxiety,
      indicated by a breathing frequency above 24 times per minute. CONCLUSIONS:
      Prostate motion is influenced by respiration in most fractions. Real-time
      intrafraction data are sensitive enough to measure the impact of respiration by
      use of wavelet decomposition methods. Although the average respiratory amplitude
      observed in this study is small, this technique provides a tool that can be
      useful if one moves to smaller treatment margins (<=5 mm). This also opens ups
      the possibility of being able to develop patient specific margins, knowing that
      prostate motion is not unpredictable.

PMID- 23871197
TI  - Group Independent Component Analysis (gICA) and Current Source Density (CSD) in
      the study of EEG in ADHD adults.
AB  - OBJECTIVE: To investigate the performance of the spectral analysis of resting
      EEG, Current Source Density (CSD) and group independent components (gIC) in
      diagnosing ADHD adults. METHODS: Power spectra of resting EEG, CSD and gIC (19
      channels, linked ears reference, eyes open/closed) from 96 ADHD and 376 healthy
      adults were compared between eyes open and eyes closed conditions, and between
      groups of subjects. RESULTS: Pattern of differences in gIC and CSD spectral power
      between conditions was approximately similar, whereas it was more widely
      spatially distributed for EEG. Size effect (Cohen's d) of differences in gIC and
      CSD spectral power between groups of subjects was considerably greater than in
      the case of EEG. Significant reduction of gIC and CSD spectral power depending on
      conditions was found in ADHD patients. Reducing power in a wide frequency range
      in the fronto-central areas is a common phenomenon regardless of whether the eyes
      were open or closed. CONCLUSIONS: Spectral power of local EEG activity isolated
      by gICA or CSD in the fronto-central areas may be a suitable marker for
      discrimination of ADHD and healthy adults. SIGNIFICANCE: Spectral analysis of gIC
      and CSD provides better sensitivity to discriminate ADHD and healthy adults.

PMID- 23871198
TI  - Similar to other forms of axonal Guillain-Barre syndrome, sensory nerves show
      reversible conduction failure in Fisher syndrome.

PMID- 23871199
TI  - Two-stage hybrid repair of a complex symptomatic celiac aneurysm.
AB  - We report the case of a novel 2-stage hybrid repair of a complex celiac artery
      aneurysm. The patient was a 42-year-old man with a proximal celiac artery
      aneurysm giving rise to distinct right and left hepatic arterial branches. Repair
      was performed using a staged approach. First, a bifurcated aortohepatic bypass
      was constructed to the common and left hepatic arteries. After recovering from
      surgery, he underwent percutaneous embolization of the aneurysm. Completion
      angiograms demonstrated flow into all celiac branches with successful thrombosis
      of the aneurysm. At 12-month follow-up, the patient had remained symptom-free
      with patent bypass grafts and complete aneurysm exclusion. We describe the
      treatment option we used, which involves repair of a complex celiac aneurysm
      using a 2-stage, open, endovascular approach. 

PMID- 23871200
TI  - Ethanol fermentation from xylose by metabolically engineered strains of
      Kluyveromyces marxianus.
AB  - We constructed a xylose-fermenting recombinant strain of thermotolerant yeast
      Kluyveromyces marxianus, DMB3-7. Both xylose consumption and ethanol production
      were remarkably increased in DMB3-7 compared to the control strain at 30 degrees
      C. Furthermore, DMB3-7 produced ethanol from xylose at both 42 degrees C and 45
      degrees C, above which xylose metabolic activity decreased. 

PMID- 23871201
TI  - Thorium(IV) removal from aqueous medium by citric acid treated mangrove
      endophytic fungus Fusarium sp. #ZZF51.
AB  - Thorium(IV) biosorption is investigated by citric acid treated mangrove
      endophytic fungus Fussarium sp. #ZZF51 (CA-ZZF51) from South China Sea. The
      biosorption process was optimized at pH 4.5, equilibrium time 90 min, initial
      thorium(IV) concentration 50 mg L(-1) and adsorbent dose 0.6 g L(-1) with 90.87%
      of removal efficiency and 75.47 mg g(-1) of adsorption capacity, which is
      obviously greater than that (11.35 mg g(-1)) of the untreated fungus Fussarium
      sp. #ZZF51 for thorium(IV) biosorption under the condition of optimization. The
      experimental data are analyzed by using isotherm and kinetic models. Kinetic data
      follow the pseudo-second-order model and equilibrium data agree very well with
      the Langmuir model. In addition, FTIR analysis indicates that hydroxyl, amino,
      and carbonyl groups act as the important roles in the adsorption process.

PMID- 23871202
TI  - NOAA's Mussel Watch Program: Incorporating contaminants of emerging concern
      (CECs) into a long-term monitoring program.

PMID- 23871203
TI  - Inhibition of larval swimming activity of the coral (Platygyra acuta) by
      interactive thermal and chemical stresses.
AB  - This study examined the interactive effects of copper and elevated temperature
      and subsequent depuration on Platygyra acuta coral larvae. Larval mortality and
      motility were significantly affected by copper alone (70% and 100% inhibition
      respectively). Their respective lethal/inhibitory concentration (LC50/IC50) were
      10-130% and 86-193% higher than those reported for other larvae. Temperature
      (ambient, 27 degrees C and elevated, 30 degrees C) alone and the combination of
      temperature and copper did not significantly affect both endpoints. This study
      provides the first quantitative data on depuration effect on resumption of larval
      motility after copper exposure, although no sign of larval recovery was observed.
      These findings suggest that the effects of copper pollution outweigh the thermal
      tolerance of coral larvae. High LC50 and IC50 recorded may be unique for corals
      from marginal reefs like Hong Kong which have already been exposed to high levels
      of copper pollution. 

PMID- 23871204
TI  - Short-term changes of fructans in ryegrass (Lolium multiflorum 'Lema') in
      response to urban air pollutants and meteorological conditions.
AB  - We investigated whether the fructan content, a storage carbohydrate, of Lolium
      multiflorum 'Lema' plants grown in a subtropical urban environment characterized
      by typical diurnal profiles of air pollutants and meteorological conditions
      changed over the course of a day during different seasons. Plants were collected
      every 2h on the last day of each two-month seasonal field experiment and
      separated into shoot (stubble or stubble+leaf blades) and roots for carbohydrate
      analyses and biomass determination. Diurnal contents of total fructose in the
      stubbles increased with high temperatures. In the roots, fructose accumulation
      showed a positive relation with hourly variations of both temperature and
      particulate matter and a negative relation with irradiance and SO2. Seasonal
      variation in shoot and root biomasses coincided with the seasonal variation of
      total fructose and were negatively affected by relative humidity and SO2,
      respectively. We concluded that hourly changes of fructans over the course of a
      day may increase the ability of L. multiflorum to tolerate short-term
      oscillations in weather and air pollution commonly observed in the subtropical
      urban environment, increasing its efficiency in monitoring air quality. 

PMID- 23871205
TI  - Complex metabolic interactions between benzo(a)pyrene and tributyltin in presence
      of dichlorodiphenyltrichloroethane in South American catfish Rhamdia quelen.
AB  - In an attempt to explore complex metabolic interactions between toxicants present
      in polluted freshwater, hepatic metabolism of benzo(a)pyrene (BaP) and
      tributyltin (TBT) in fish was investigated when these compounds were
      administrated alone, mixed together and along with
      dichlorodiphenyltrichloroethane (DDT). Ten Rhamdia quelen per group were treated
      with a single intra-peritoneal (IP) dose (5-day experiment) or three successive
      doses (15-day experiment) either containing BaP (0.3; 3 or 30mgkg(-1)) or TBT
      (0.03; 0.3 or 3mgkg(-1)) or a combination of BaP+TBT, BaP+DDT, TBT+DDT and
      BaP+TBT+DDT under their respective lower doses, with DDT dose kept at 0.03mgkg(
      1). Tetrahydroxy-benzo(a)pyrene (BaP-tetrol-I), and dibutyltin (DBT) and
      monobutyltin (MBT) were analyzed to assess BaP and TBT hepatic metabolism,
      respectively. A significant difference in BaP-tetrol-I concentration was observed
      in liver and bile between the lowest and the highest doses of BaP in both 5 and
      15-day experiments. In the 15-day experiment, the presence of TBT with BaP
      reduced the amount of BaP-tetrol-I in bile compared to the BaP alone. The time of
      exposure and the number of doses affected BaP-tetrol-I concentration in the bile
      of fish exposed to BaP 0.3mgkg(-1) and BaP+DDT. TBT and its metabolites
      concentrations showed a dose-dependent increase in the liver in both experiments
      and in the bile in the 5-day experiment. TBT at its lowest dose was completely
      metabolized into DBT and MBT in the liver in the 15-day experiment. No TBT
      metabolites were detected in the bile of fish exposed to the mixtures in the 5
      day experiment, except for a small MBT amount found in BaP+TBT+DDT. This study
      strengthens the hypothesis of a metabolic interaction between BaP and TBT in fish
      and suggests DDT as an important third player when present in the mixture. 

PMID- 23871206
TI  - Sources, distribution and potential risks of pharmaceuticals and personal care
      products in Qingshan Lake basin, Eastern China.
AB  - In this study, we examined the occurrence and distribution of 12 selected
      pharmaceutical and personal care products (PPCPs) in Qingshan Lake basin and
      evaluated their potential ecological risks. Caffeine was the dominant compound
      among all selected PPCPs in the aqueous phase (23.8-344.7ng/L). Sediment release
      contributed minimally to caffeine levels found in the aqueous phase of Qingshan
      Lake. Concentrations of selected PPCPs in dry season water samples were generally
      higher than those in the water samples obtained during the wet or median water
      seasons. The risks of residual caffeine in water on aqueous organisms was minimal
      (risk quotient values below 0.01). Sulfamethoxazole and triclocarban posed the
      highest environmental risks despite their low concentrations (below 25ng/L in
      water and 10MUg/kg in sediment) in Qingshan Lake basin. The risks produced by
      selected PPCPs in sediments were generally higher than in the aqueous phase. 

PMID- 23871207
TI  - Antagonistic regulation by the transcription factors C/EBPalpha and MITF
      specifies basophil and mast cell fates.
AB  - It remains unclear whether basophils and mast cells are derived from a common
      progenitor. Furthermore, how basophil versus mast cell fate is specified has not
      been investigated. Here, we have identified a population of granulocyte
      macrophage progenitors (GMPs) that were highly enriched in the capacity to
      differentiate into basophils and mast cells while retaining a limited capacity to
      differentiate into myeloid cells. We have designated these progenitor cells "pre
      basophil and mast cell progenitors" (pre-BMPs). STAT5 signaling was required for
      the differentiation of pre-BMPs into both basophils and mast cells and was
      critical for inducing two downstream molecules: C/EBPalpha and MITF. We have
      identified C/EBPalpha as the critical basophil transcription factor for
      specifying basophil cell fate and MITF as the crucial transcription factor for
      specifying mast cell fate. C/EBPalpha and MITF silenced each other's
      transcription in a directly antagonistic fashion. Our study reveals how basophil
      and mast cell fate is specified. 

PMID- 23871210
TI  - Interprofessional service improvement learning and patient safety: a content
      analysis of pre-registration students' assessments.
AB  - A culture of continuous service improvement underpins safe, efficient and cost
      effective health and social care. This paper reports a qualitative research study
      of assessment material from one cohort of final year pre-registration health and
      social care students' interprofessional service improvement learning experience.
      Initially introduced to the theory of service improvement, students were linked
      with an interprofessional buddy group, and subsequently planned and implemented,
      if possible, a small scale service improvement project within a practice
      placement setting. Assessment was by oral project presentation and written
      reflection on learning. Summative assessment materials from 150 students were
      subjected to content analysis to identify: service user triggers for service
      improvement; ideas to address the identified area for improvement; and
      perceptions of service improvement learning. Triggers for service improvements
      included service user disempowerment, poor communication, gaps in service
      provision, poor transitions, lack of information, lack of role clarity and role
      duplication, and differed between professions. Ideas for improvement included
      both the implementation of evidence based best practice protocols in a local
      context and also innovative approaches to problem solving. Students described
      both intrapersonal and interprofessional learning as a result of engaging with
      service improvement theory and practice. Service improvement learning in an
      interprofessional context has positive learning outcomes for health and social
      care students. Students can identify improvement opportunities that may otherwise
      go undetected. Engaging positively in interprofessional service improvement
      learning as a student is an important rehearsal for life as a qualified
      practitioner. It can help students to develop an ability to challenge unsafe
      practice elegantly, thereby acting as advocates for the people in their care.
      Universities can play a key support role by working collaboratively with service
      organisations; role modelling effective interprofessional working; and supporting
      research to measure the impact of education on practice. 

PMID- 23871208
TI  - The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven,
      type 1 interferon-dependent immunity.
AB  - Immune cells sense microbial products through Toll-like receptors (TLR), which
      trigger host defense responses including type 1 interferons (IFNs) secretion. A
      coding polymorphism in the protein tyrosine phosphatase nonreceptor type 22
      (PTPN22) gene is a susceptibility allele for human autoimmune and infectious
      disease. We report that Ptpn22 selectively regulated type 1 IFN production after
      TLR engagement in myeloid cells. Ptpn22 promoted host antiviral responses and was
      critical for TLR agonist-induced, type 1 IFN-dependent suppression of
      inflammation in colitis and arthritis. PTPN22 directly associated with TNF
      receptor-associated factor 3 (TRAF3) and promotes TRAF3 lysine 63-linked
      ubiquitination. The disease-associated PTPN22W variant failed to promote TRAF3
      ubiquitination, type 1 IFN upregulation, and type 1 IFN-dependent suppression of
      arthritis. The findings establish a candidate innate immune mechanism of action
      for a human autoimmunity "risk" gene in the regulation of host defense and
      inflammation. 

PMID- 23871209
TI  - The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome.
AB  - The NLRP3 inflammasome plays a major role in innate immune responses by
      activating caspase-1, resulting in secretion of interleukin-18 (IL-18) and IL
      1beta. Although cytosolic double-stranded RNA (dsRNA) and bacterial RNA are known
      to activate the NLRP3 inflammasome, the upstream sensor is unknown. We
      investigated the potential function of DExD/H-box RNA helicase family members
      (previously shown to sense cytosolic DNA and RNA to induce type 1 interferon
      responses) in RNA-induced NLRP3 inflammasome activation. Among the helicase
      family members tested, we found that targeting of DHX33 expression by short
      hairpin RNA efficiently blocked the activation of caspase-1 and secretion of IL
      18 and IL-1beta in human macrophages that were activated by cytosolic poly I:C,
      reoviral RNA, or bacterial RNA. DHX33 bound dsRNA via the helicase C domain.
      DHX33 interacted with NLRP3 and formed the inflammasome complex following
      stimulation with RNA. We therefore identified DHX33 as a cytosolic RNA sensor
      that activates the NLRP3 inflammasome. 

PMID- 23871211
TI  - Periorbital necrobiosis lipoidica.

PMID- 23871212
TI  - Cartilage graft in the reconstruction of the pinna of the ear.

PMID- 23871213
TI  - The expression ratio of miR-17-5p and miR-155 correlates with grading in canine
      splenic lymphoma.
AB  - In dogs as in humans, microRNAs (miRNAs) play a key role in normal and neoplastic
      hematopoiesis regulation. The general miRNA expression framework varies among
      different stages of development and differentiation of tumors, and miRNAs are
      widely investigated as new molecular tools for cancer diagnosis and
      classification. Canine lymphomas are currently classified according with the WHO
      classification, but a comprehensive grading study of clinical samples is still
      lacking, and molecular tools for quick grading are not yet available. In the
      present work, a retrospective study of the expression profile of a panel of
      miRNAs in canine primary splenic lymphomas was performed. The formalin fixed,
      paraffin embedded (FFPE) lymphoma samples were accurately classified according
      with the WHO classification, and were analyzed for miRNA expression using stem
      loop TaqMan real time RT-PCR. For each miRNA investigated, relative and absolute
      quantification were performed after selecting the best housekeeping genes using
      the NormFinder and geNorm algorithms. The results of this study show a diversity
      in miRNA expression in low (L) grade lymphomas compared to intermediate-high (I
      H) grade lymphomas. The molar ratio between miR-17-5p and miR-155 correlated with
      WHO grading. These results highlight the potential use of miR-17-5p/miR-155 molar
      ratio as a new molecular tool for grading of canine splenic lymphomas. The data
      here reported further support the utility of monitoring miRNA expression in
      canine hematopoietic malignancies diagnosis and prognosis. 

PMID- 23871214
TI  - Functional characterization of porcine LSm14A in IFN-beta induction.
AB  - Human LSm14A has recently been found as a processing body-associated sensor of
      intracellular viral nucleic acids and triggers signaling for type I IFN
      expression. Here porcine LSm14A (pLSm14A) was cloned from the PK-15 cells. The
      pLSm14A ORF is 1392 bp in length, encoding 463 amino acids. The putative pLSm14A
      contains a Sm-like domain and two arginine-glycine-glycine (RGG) boxes. The
      pLSm14A has high identity at the amino acid level to those of bovine, human and
      mouse (93.5-97.4%) and is transcribed in different tissues of pigs. In HEK293 or
      Marc-145 cells, pLSm14A was localized in the cytosol as P-body-like dots.
      Expression of pLSm14A in HEK293 or Marc-145 cells enhanced activities of IFN-beta
      and NF-kappaB promoters, induced IFN-beta transcription, and potentiated
      poly(I:C)-induced IFN-beta promoter activation, indicating that pLSm14A is a
      potential signal molecule in the IFN-beta pathway of pigs. We also found that
      pLSm14A-induced IFN-beta promoter activity was down-regulated by porcine
      reproductive and respiratory syndrome virus infection in Marc-145 cells. Since
      pLSm14A is constitutively expressed in virtually all tissues, more research is
      needed to explore its role in initial phase of viral infections of pigs and its
      relationship with RIG-I in sensing PAMPs for type I IFN induction.

PMID- 23871215
TI  - Polyamines: emerging players in bacteria-host interactions.
AB  - Polyamines are small polycationic molecules found in almost all cells and
      associated with a wide variety of physiological processes. In recent years it has
      become increasingly clear that, in addition to core physiological functions,
      polyamines play a crucial role in bacterial pathogenesis. Considerable evidence
      has built up that bacteria have evolved mechanisms to turn these molecules to
      their own advantage and a novel standpoint to look at host-bacterium interactions
      emerges from the interplay among polyamines, host cells and infecting bacteria.
      In this review, we highlight how human bacterial pathogens have developed their
      own resourceful strategies to exploit polyamines or manipulate polyamine-related
      processes to optimize their fitness within the host. Besides contributing to a
      better understanding of the complex relationship between a pathogen and its host,
      acquisitions in this field have a significant potential towards the development
      of novel antibacterial therapeutic approaches. 

PMID- 23871216
TI  - Neurite pruning and neuronal cell death: spatial regulation of shared destruction
      programs.
AB  - During development, neurons are initially overproduced and excess neurons are
      eliminated later on by programmed cell death. In a more refined developmental
      process termed pruning, excess axons and dendritic branches are removed while the
      cell body remains intact. In mature animals, axons that become disconnected as a
      result of injury are eliminated through a series of events collectively known as
      Wallerian degeneration. Recent evidence points to unexpected similarities between
      these three types of obliterative processes, as they share common regulators.
      These findings provide new ideas on how cellular destruction programs are
      spatially regulated in neurons. 

PMID- 23871217
TI  - Role of glia in developmental synapse formation.
AB  - Neuronal synapse formation and maturation in the developing brain is a complex
      multi-step process, and it is now clear that glial cells, in particular
      astrocytes, are key regulators of neuronal synaptogenesis. This article reviews
      the progress made in the past few years in identifying molecular mechanisms that
      glial cells use to regulate neuronal synaptogenesis. The focus is on novel glial
      molecules that induce synapse formation, inhibit synapse formation, or control
      synaptic levels of glutamate receptors. A role for glial cells in the pathology
      of neurodevelopmental disorders is discussed. 

PMID- 23871218
TI  - Adult male professional soccer players have higher lumbar spine and hip bone
      mineral density than age- and body weight-matched controls.

PMID- 23871219
TI  - High-risk human papillomavirus E6 inhibits monocyte differentiation to Langerhans
      cells.
AB  - High-risk human papillomaviruses (HPVs) cause a variety of malignancies of the
      mucosal epithelium. However, the local immune evasion strategies used by HPV
      transformed cells remain unclear. Here, we examined the effect of HPV-positive
      cancer cells on human peripheral blood monocytes, which are precursors of
      Langerhans cells, key antigen-presenting cells in the squamous epithelium. HPV
      positive cervical cancer cells and HPV-E6 expressing cells inhibited monocyte
      differentiation to Langerhans cells in a contact-dependent manner. Unlike
      Langerhans cells, monocytes that differentiated in the presence of HPV16 E6
      expressing cells exhibited high levels of endocytic activity. Our results suggest
      that cells infected by high-risk HPV evade immune surveillance by blocking the
      differentiation of monocytes into competent antigen presenting cells. 

PMID- 23871220
TI  - Development and application of a blocking enzyme-linked immunosorbent assay
      (ELISA) to differentiate antibodies against live and inactivated porcine
      reproductive and respiratory syndrome virus.
AB  - The aim of this study was to establish a method that could differentiate
      antibodies against live and inactivated vaccines of porcine reproductive and
      respiratory syndrome virus (PRRSV). A blocking ELISA (b-ELISA) was established
      using the PRRSV non-structural protein, Nsp9, as the antigen and a monoclonal
      antibody, 2D6, against the Nsp9 protein as the capture antibody. The test was
      validated by using 415 clinical sera in the b-ELISA compared to a commercial kit
      based on the indirect ELISA using the nucleocapsid (N) protein as antigen.
      Significant differences were observed for the data obtained by the two detection
      methods. This may be due to the commercial kit detecting antibodies elicited by
      live and inactivated virus, whereas the b-ELISA only detects antibodies produced
      by any active viral replication, such as natural infection or live vaccination.
      Therefore, the b-ELISA in this study is able to distinguish between antibodies
      against live and inactivated viruses in pigs. 

PMID- 23871221
TI  - A monosaccharide-modified peptide phage library for screening of ligands to
      carbohydrate-binding proteins.
AB  - A monosaccharide-modified beta-loop peptide library displayed on phage has been
      constructed and used for the screening of glycopeptide ligands against a
      carbohydrate-binding protein. The beta-loop peptide library was designed and
      modified with a mannose derivative on phage. The glycopeptide ligands to
      concanavalin A (ConA), a mannose-binding protein, were obtained from the mannose
      modified peptide phage library. The amino acids neighboring the mannose unit of
      glycopeptides not only reinforced the binding affinity but also gave diverse
      binding characteristics. 

PMID- 23871222
TI  - Regioselective synthesis of 6-aryl-benzo[h][1,2,4]-triazolo[5,1-b]quinazoline-7,8
      diones as potent antitumoral agents.
AB  - Three-component coupling of aldehyde, 2-hydroxy-1,4-naphthoquinone and 3-amino
      1,2,4-triazole has been achieved using a catalytic amount of sulfamic acid under
      solvent free conditions to produce a novel series of 6-aryl-benzo[h][1,2,4]
      triazolo[5,1-b]quinazoline-7,8-dione derivatives in good yields and with high
      regioselectivity. These compounds are found to exhibit potent antitumoral
      properties. 

PMID- 23871223
TI  - Using case reports to determine when liver bleeding occurs during disease
      progression in HELLP syndrome.
AB  - BACKGROUND: Hepatic hemorrhage occurs in less than 5% of patients with hemolysis,
      elevated liver enzymes, low platelets (HELLP) syndrome but it is a profound cause
      of maternal/perinatal morbidity and mortality. OBJECTIVES: To determine when
      liver bleeding occurs during the development of HELLP syndrome. SEARCH STRATEGY:
      The English literature was searched for all reports of HELLP syndrome associated
      with liver bleeding. SELECTION CRITERIA: Eighty-seven case summaries of liver
      bleeding in the setting of HELLP syndrome were included. The standard definition
      of HELLP syndrome was used with expansion into the Mississippi classification
      system, supplemented by patients with partial HELLP syndrome. DATA COLLECTION AND
      ANALYSIS: Demographic and clinical data were collected and recorded in an Excel
      database. MAIN RESULTS: Liver bleeding was detected in 18 (20.7%) patients with
      class 1 HELLP syndrome, 24 (27.6%) with class 2 HELLP syndrome, and 12 (13.8%)
      with class 3 or partial HELLP syndrome. In 33 (37.9%) patients, the exact class
      of HELLP syndrome at the time liver bleeding was detected could not be determined
      from the published descriptions. CONCLUSIONS: Liver bleeding can occur early
      during HELLP syndrome development, not only in patients with advanced, class 1
      illness.

PMID- 23871224
TI  - Gold nanoparticles: a paradigm shift in biomedical applications.
AB  - In the medical field, majority of the active ingredients exists in the form of
      solid particle (90% of all medicines). Nanotechnology had grabbed the attention
      of many scientists working in different aspects and gave them a vivid imagination
      in order to utilize the nanotechnology in an innovative way according to their
      needs. One of the major applications of nanotechnology is drug delivery through
      nanoparticles which is on boom for the researchers and gives a challenging
      environment for the researchers. Among them upcoming challenge is the use of
      inorganic nanoparticles for the drug delivery and related aspects. There is
      growing interests in usage of inorganic nanoparticles in medicine due to their
      size, and unique physical properties that make them different from other
      nanoparticulate systems. This review will lay special emphasis on the uniqueness
      of inorganic nanoparticles especially gold nanoparticles as a drug delivery
      vehicle and moreover will present a wide spread scenario of gold nanoparticles
      that has been used for treatment of life threatening diseases like cancer. 

PMID- 23871225
TI  - Application of cognitive interviewing to improve self-administered questionnaires
      used in small scale social pharmacy research.
AB  - Validating questionnaires for social pharmacy research with smaller sample sizes
      can be unnecessarily time-consuming and costly, a solution to this is cognitive
      interviewing with 2 interviews per iteration. This paper shows how cognitive
      interviewing with pairs of interviews per iteration of the questionnaire can be
      used to identify overt and covert issues with comprehension, retrieval, judgment
      and response experienced by respondents when attempting to answer a question or
      navigate around the questionnaire. When used during questionnaire development in
      small scale social pharmacy research studies cognitive interviewing can reduce
      both respondent burden and response error and should result in more reliable
      survey results. The process of cognitive interviewing is illustrated by a case
      study from the development of the Perspectives on Progesterone questionnaire. 

PMID- 23871226
TI  - Swedish teenagers and over-the-counter analgesics - responsible, casual or
      careless use.
AB  - BACKGROUND: Teenagers in Sweden were given greater access as consumers of OTC
      drugs in 2009 after the reregulation of the pharmacy market, which allowed for
      the establishment of private pharmacies and sale of specific over-the-counter
      (OTC) drugs in retail stores and gas stations. Increased access to OTC drugs
      could provide new opportunities for self-care but attenuates the opportunity for
      the traditional expert surveillance of pharmacists, thus increasing the
      possibility of inappropriate OTC drug use. OBJECTIVES: Views of 16-19 year old
      Swedish teenagers on OTC drugs, with special regard to analgesic drugs were
      explored and described, based on the following questions: How and where did they
      acquire their knowledge and attitudes regarding OTC drugs? What perceptions did
      they have about the use of OTC drugs? METHODS: A qualitative approach with a
      descriptive design was chosen. Data were collected in 2011 with 10 focus group
      discussions with high school students aged 16-19 years from different parts of
      Sweden. A total of 77 teenagers participated, 33 males and 44 females. A manifest
      qualitative content analysis was performed. RESULTS: While most teenagers
      appeared to have responsible attitudes toward OTC drugs and their use, some
      teenagers had attitudes that ranged from casual to careless. The focus group
      discussions also revealed knowledge gaps among teenagers regarding OTC drugs, and
      the significant influence of parents and peers on their OTC drug use.
      CONCLUSIONS: This study provides insight into how vulnerable some teenagers could
      be as new consumers of OTC drugs and suggested that educational efforts could be
      geared toward parents as well as teenagers.

PMID- 23871227
TI  - Decision-making during initiation of medication therapy.
AB  - BACKGROUND: Individuals' frequent and consistent interaction with medications can
      serve as a unifying element to help coordinate individuals' health care services.
      Despite its potential to improve coordination of heath care, initiation of
      medication therapy from the perspective of individuals' experiences remains
      largely unexamined. OBJECTIVES: The objectives for this study were to describe
      the viewpoints of consumers, physicians, pharmacists, and social workers
      regarding initiation of medication therapy in terms of: (1) activation and
      engagement, (2) information processing, and (3) economic factors. METHODS: Data
      were collected via mailed survey methodology from random samples of 400 adults,
      400 physicians, 400 pharmacists, and 400 social workers residing in Minnesota.
      Responses to open-ended questions were coded using content analysis and
      summarized with descriptive statistics. RESULTS: The findings showed that
      consumer views of (1) activation and engagement, (2) information processing, and
      (3) economic factors differed from the views of physicians, pharmacists, and
      social workers. Consumers typically view initiation of medication therapy within
      the context of their overall lives. Physicians view it as a biomedical puzzle in
      which diagnosis, drug product selection, and risk assessment are main concerns.
      Pharmacists view it as a health care systems puzzle in which insurance coverage,
      cost, and risk management are main concerns. Social workers view it as a social
      systems puzzle in which access to care, cost, and social support are main
      concerns. CONCLUSIONS: Initiation of medication therapy is a disjointed
      experience for many consumers. The best timing for providing information about
      prescription drugs to individuals depends largely on what kinds of thoughts and
      impressions they have about a new therapy at various stages of the medication use
      process. The findings from this study can be useful for (1) developing consumer
      centered approaches for medication use and (2) coordinating health care through
      the integration of the medication experience using consumer viewpoints.

PMID- 23871228
TI  - Nicotine increases lifespan and rescues olfactory and motor deficits in a
      Drosophila model of Parkinson's disease.
AB  - Drosophila melanogaster is an attractive model of familial Parkinson's disease,
      as flies with loss-of-function mutations of the parkin gene exhibit many
      pathologies observed in PD patients. Progressive motor deficits found in
      homozygous parkin mutants seem to result from mitochondrial pathology that causes
      indirect flight muscle and dopaminergic neuronal degeneration [1,2]. We have
      found that heterozygous parkin mutants have decreased lifespan, generally
      progressive motor dysfunction and olfactory deficits compared to control flies,
      suggesting that mutation of this gene produces a dominant phenotype. Tobacco
      smokers are dose-dependently less likely to develop PD [3,4]; subsequent in vitro
      and in vivo studies show that nicotine is protective in models of sporadic PD
      [6]. Literature addressing the potential protection by nicotine in Parkin loss-of
      function models spans limited concentrations and selected time points in the
      organism's lifespan. We have found that parkin heterozygotes have late-onset
      climbing and flying deficits as well as decreased viability and olfactory
      deficits that precede motor defects. While chronic nicotine exposure decreases
      lifespan and climbing and flying abilities in control flies, it can improve
      viability and flying capability as well as rescue climbing and olfactory deficits
      in parkin heterozygotes. Dopaminergic neurons are spared in the parkin
      heterozygote, perhaps because this phenotype is less severe than in the
      homozygous parkin mutants. Nicotine pretreatment may be protective in sporadic PD
      patients and models; however, timely diagnosis remains to be an obstacle. Our
      results suggest that nicotine also may be protective in familial PD patients, who
      can be easily identified before motor symptoms occur. 

PMID- 23871229
TI  - Melatonin in rapid eye movement sleep behavior disorder: why does it work?

PMID- 23871230
TI  - A decade of reversal: an analysis of 146 contradicted medical practices.
AB  - OBJECTIVE: To identify medical practices that offer no net benefits. METHODS: We
      reviewed all original articles published in 10 years (2001-2010) in one high
      impact journal. Articles were classified on the basis of whether they addressed a
      medical practice, whether they tested a new or existing therapy, and whether
      results were positive or negative. Articles were then classified as 1 of 4 types:
      replacement, when a new practice surpasses standard of care; back to the drawing
      board, when a new practice is no better than current practice; reaffirmation,
      when an existing practice is found to be better than a lesser standard; and
      reversal, when an existing practice is found to be no better than a lesser
      therapy. This study was conducted from August 1, 2011, through October 31, 2012.
      RESULTS: We reviewed 2044 original articles, 1344 of which concerned a medical
      practice. Of these, 981 articles (73.0%) examined a new medical practice, whereas
      363 (27.0%) tested an established practice. A total of 947 studies (70.5%) had
      positive findings, whereas 397 (29.5%) reached a negative conclusion. A total of
      756 articles addressing a medical practice constituted replacement, 165 were back
      to the drawing board, 146 were medical reversals, 138 were reaffirmations, and
      139 were inconclusive. Of the 363 articles testing standard of care, 146 (40.2%)
      reversed that practice, whereas 138 (38.0%) reaffirmed it. CONCLUSION: The
      reversal of established medical practice is common and occurs across all classes
      of medical practice. This investigation sheds light on low-value practices and
      patterns of medical research.

PMID- 23871231
TI  - How many contemporary medical practices are worse than doing nothing or doing
      less?

PMID- 23871232
TI  - TMC1 and TMC2 are components of the mechanotransduction channel in hair cells of
      the mammalian inner ear.
AB  - Sensory transduction in auditory and vestibular hair cells requires expression of
      transmembrane channel-like (Tmc) 1 and 2 genes, but the function of these genes
      is unknown. To investigate the hypothesis that TMC1 and TMC2 proteins are
      components of the mechanosensitive ion channels that convert mechanical
      information into electrical signals, we recorded whole-cell and single-channel
      currents from mouse hair cells that expressed Tmc1, Tmc2, or mutant Tmc1. Cells
      that expressed Tmc2 had high calcium permeability and large single-channel
      currents, while cells with mutant Tmc1 had reduced calcium permeability and
      reduced single-channel currents. Cells that expressed Tmc1 and Tmc2 had a broad
      range of single-channel currents, suggesting multiple heteromeric assemblies of
      TMC subunits. The data demonstrate TMC1 and TMC2 are components of hair cell
      transduction channels and contribute to permeation properties. Gradients in TMC
      channel composition may also contribute to variation in sensory transduction
      along the tonotopic axis of the mammalian cochlea.

PMID- 23871234
TI  - Inter-insertional distance is a poor correlate for ligament load: analysis from
      in vivo gait kinetics data.
AB  - In many analytic models of the knee joint, inter-insertional distance is used as
      the measure to define the load in a ligament. In addition, the direction of the
      load is taken to be the direction between the two insertions. Our in vivo data on
      the ovine ligament loads during gait, however, indicate that a wide range of
      forces is possible in the ligament for any specified inter-insertional distance.
      To understand the complex relationship between the bone orientations and ligament
      load better, an artificial neural network (ANN) model was developed. The six
      degree-of-freedom (6-DOF) in vivo kinematics of femur relative to tibia (joint
      kinematics) was used as input, and the magnitude of the anterior cruciate
      ligament (ACL) load was used as output/target. While the trained network was able
      to predict peak ligament loads with remarkable accuracy (R-square=0.98), an
      explicit relationship between joint kinematics and ACL load could not be
      determined. To examine the experimental and ANN observations further, a finite
      element (FE) model of the ACL was created. The geometry of the FE model was
      reconstructed from magnetic resonance images (MRI) of an ACL, and an isotropic,
      hyperelastic, nearly incompressible constitutive model was implemented for the
      ACL. The FE simulation results also indicate that a range of loads is possible in
      the ACL for a given inter-insertional distance, in concordance with the
      experimental/ANN observations. This study provides new insights for models of the
      knee joint; a simple force-length relationship for the ligament is not exact, nor
      is a single point to single point direction. More detailed microstructure
      function data is required. 

PMID- 23871233
TI  - Nicotine decreases ethanol-induced dopamine signaling and increases self
      administration via stress hormones.
AB  - Tobacco smoking is a well-known risk factor for subsequent alcohol abuse, but the
      neural events underlying this risk remain largely unknown. Alcohol and nicotine
      reinforcement involve common neural circuitry, including the mesolimbic dopamine
      system. We demonstrate in rodents that pre-exposure to nicotine increases alcohol
      self-administration and decreases alcohol-induced dopamine responses. The blunted
      dopamine response was due to increased inhibitory synaptic transmission onto
      dopamine neurons. Blocking stress hormone receptors prior to nicotine exposure
      prevented all interactions with alcohol that we measured, including the increased
      inhibition onto dopamine neurons, the decreased dopamine responses, and the
      increased alcohol self-administration. These results indicate that nicotine
      recruits neuroendocrine systems to influence neurotransmission and behavior
      associated with alcohol reinforcement.

PMID- 23871235
TI  - Accuracy of gastrocnemius muscles forces in walking and running goats predicted
      by one-element and two-element Hill-type models.
AB  - Hill-type models are commonly used to estimate muscle forces during human and
      animal movement-yet the accuracy of the forces estimated during walking, running,
      and other tasks remains largely unknown. Further, most Hill-type models assume a
      single contractile element, despite evidence that faster and slower motor units,
      which have different activation-deactivation dynamics, may be independently or
      collectively excited. This study evaluated a novel, two-element Hill-type model
      with "differential" activation of fast and slow contractile elements. Model
      performance was assessed using a comprehensive data set (including measures of
      EMG intensity, fascicle length, and tendon force) collected from the
      gastrocnemius muscles of goats during locomotor experiments. Muscle forces
      predicted by the new two-element model were compared to the forces estimated
      using traditional one-element models and to the forces measured in vivo using
      tendon buckle transducers. Overall, the two-element model resulted in the best
      predictions of in vivo gastrocnemius force. The coefficient of determination,
      r(2), was up to 26.9% higher and the root mean square error, RMSE, was up to
      37.4% lower for the two-element model than for the one-element models tested. All
      models captured salient features of the measured muscle force during walking,
      trotting, and galloping (r(2)=0.26-0.51), and all exhibited some errors
      (RMSE=9.63-32.2% of the maximum in vivo force). These comparisons provide
      important insight into the accuracy of Hill-type models. The results also show
      that incorporation of fast and slow contractile elements within muscle models can
      improve estimates of time-varying, whole muscle force during locomotor tasks. 

PMID- 23871236
TI  - Right internal jugular venous cannulation complicated by tension hydrothorax.
AB  - Central Venous Catheter (CVC) is a common procedure performed in patients'
      management, especially the critically ill ones. CVC has been used as main access
      in patients requiring large amount of fluid resuscitation, total parenteral
      nutrition or measuring the central venous pressure. Although most complications
      associated with central venous cannulation are minimal, local and easy to
      control, others may be critical and rapidly fatal if not recognized and treated
      immediately. One of the most serious incidents that can occur post CVC placement
      is delayed hydrothorax. It usually results from migration and perforation of the
      catheter through the SVC wall. In this report, we describe a case of tension
      hydrothorax that occurred a few hours after placement of CVC in the right
      internal jugular vein. In acutely ill patients that are already unstable, making
      the diagnosis of tension hydrothorax secondary to CVC placement requires high
      level of suspicion. Prompt pleural effusion drainage like in our case is crucial
      for favorable outcome. 

PMID- 23871237
TI  - Are you living your legacy?

PMID- 23871238
TI  - Reversal of fish stock decline in the Northeast Atlantic.
AB  - Analyses of global fish stocks paint a mixed picture of success, with some
      holding fishery management responsible for the poor status of many stocks [1-3]
      or predicting widespread collapse [1, 4]. Some suggest a stable [5] or improving
      situation [6] in certain jurisdictions. The debate is particularly polarized in
      the European Union, where the Common Fisheries Policy (CFP) has been criticized
      for failing to protect stocks [2, 7-10], while others argue that a rebuilding
      process is underway [11, 12]. We show that substantial change in stock trends
      occurred in the area around the turn of the century: since then, the fishing
      pressure (as measured by the exploitation rate) has reduced continuously and
      there have been increases in biomass, demonstrating the potential for stock
      recovery. In 2011, for the first time, the majority of assessed stocks, where
      reference points are defined, were fished sustainably. The reductions in fishing
      pressure were associated with declines in fishing effort. The last reform of the
      CFP, in 2002, introduced effort control as part of more enforceable management
      measures, which were also based on longer-term plans. Further reforms to the CFP
      are currently being developed, so it is important, when correcting its
      weaknesses, to also acknowledge and build on the success of a major reduction in
      the fishing pressure on European fish stocks. 

PMID- 23871239
TI  - Shared representations for working memory and mental imagery in early visual
      cortex.
AB  - Early visual areas contain specific information about visual items maintained in
      working memory, suggesting a role for early visual cortex in more complex
      cognitive functions [1-4]. It is an open question, however, whether these areas
      also underlie the ability to internally generate images de novo (i.e., mental
      imagery). Research on mental imagery has to this point focused mostly on whether
      mental images activate early sensory areas, with mixed results [5-7]. Recent
      studies suggest that multivariate pattern analysis of neural activity patterns in
      visual regions can reveal content-specific representations during cognitive
      processes, even though overall activation levels are low [1-4]. Here, we used
      this approach [8, 9] to study item-specific activity patterns in early visual
      areas (V1-V3) when these items are internally generated. We could reliably decode
      stimulus identity from neural activity patterns in early visual cortex during
      both working memory and mental imagery. Crucially, these activity patterns
      resembled those evoked by bottom-up visual stimulation, suggesting that mental
      images are indeed "perception-like" in nature. These findings suggest that the
      visual cortex serves as a dynamic "blackboard" [10, 11] that is used during both
      bottom-up stimulus processing and top-down internal generation of mental content.

PMID- 23871240
TI  - Passive joint forces are tuned to limb use in insects and drive movements without
      motor activity.
AB  - BACKGROUND: Limb movements are generally driven by active muscular contractions
      working with and against passive forces arising in muscles and other structures.
      In relatively heavy limbs, the effects of gravity and inertia predominate,
      whereas in lighter limbs, passive forces intrinsic to the limb are of greater
      consequence. The roles of passive forces generated by muscles and tendons are
      well understood, but there has been little recognition that forces originating
      within joints themselves may also be important, and less still that these joint
      forces may be adapted through evolution to complement active muscle forces acting
      at the same joint. RESULTS: We examined the roles of passive joint forces in
      insect legs with different arrangements of antagonist muscles. We first show that
      passive forces modify actively generated movements of a joint across its working
      range, and that they can be sufficiently strong to generate completely passive
      movements that are faster than active movements observed in natural behaviors. We
      further demonstrate that some of these forces originate within the joint itself.
      In legs of different species adapted to different uses (walking, jumping), these
      passive joint forces complement the balance of strength of the antagonist muscles
      acting on the joint. We show that passive joint forces are stronger where they
      assist the weaker of two antagonist muscles. CONCLUSIONS: In limbs where the
      dictates of a key behavior produce asymmetry in muscle forces, passive joint
      forces can be coadapted to provide the balance needed for the effective
      generation of other behaviors.

PMID- 23871241
TI  - Cdk1 modulation ensures the coordination of cell-cycle events during the switch
      from meiotic prophase to mitosis.
AB  - BACKGROUND: Budding yeast cells that enter the developmental path of meiosis do
      not commit to finishing meiosis until after prophase I and the realization of
      such meiosis-specific events as pairing of homologous chromosomes and initiation
      of recombination. If the meiosis-inducing signal is withdrawn prior to
      commitment, cells exit meiosis and return to mitosis. The timing of this
      transition poses a singular problem for maintaining genome integrity. Cells in
      meiotic prophase have already replicated their DNA, but they have not undergone
      the morphological changes intrinsic to mitosis, including budding. Successful re
      entry into mitosis requires that these cells bud but not rereplicate their DNA,
      reversing the normal order of mitosis. This study focuses on the cellular
      mechanisms that permit this dramatically altered order of cell-cycle events.
      RESULTS: By developing a microfluidics assay to monitor individual cells, we show
      that the successful transition from meiotic prophase to mitosis requires the
      modulation of Cdk1 activity to coordinate cell-cycle events. The S. cerevisiae
      Wee1 homolog Swe1 prevents the formation of multinucleate cells by restraining M
      phase CDK activity to allow bud formation prior to nuclear division. The
      remaining S phase CDK activity promotes bud formation and prevents origin
      licensing so that DNA cannot rereplicate between bud formation and nuclear
      division. Once a bud has formed, M phase CDK drives cells through a normal
      mitotic division. CONCLUSIONS: Our study uncovers the essential requirement of
      Swe1 to modulate CDK activity to coordinate cell-cycle events and maintain genome
      integrity during the transition from meiotic prophase to mitosis.

PMID- 23871242
TI  - Memory for distant past events in chimpanzees and orangutans.
AB  - Determining the memory systems that support nonhuman animals' capacity to
      remember distant past events is currently the focus an intense research effort
      and a lively debate [1-3]. Comparative psychology has largely adopted Tulving's
      framework by focusing on whether animals remember what-where-when something
      happened (i.e., episodic-like memory) [4-6]. However, apes have also been
      reported to recall other episodic components [7] after single-trial exposures [8,
      9]. Using a new experimental paradigm we show that chimpanzees and orangutans
      recalled a tool-finding event that happened four times 3 years earlier
      (experiment 1) and a tool-finding unique event that happened once 2 weeks earlier
      (experiment 2). Subjects were able to distinguish these events from other tool
      finding events, which indicates binding of relevant temporal-spatial components.
      Like in human involuntary autobiographical memory, a cued, associative retrieval
      process triggered apes' memories: when presented with a particular setup,
      subjects instantaneously remembered not only where to search for the tools
      (experiment 1), but also the location of the tool seen only once (experiment 2).
      The complex nature of the events retrieved, the unexpected and fast retrieval,
      the long retention intervals involved, and the detection of binding strongly
      suggest that chimpanzees and orangutans' memories for past events mirror some of
      the features of human autobiographical memory. 

PMID- 23871243
TI  - Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce
      lipotoxicity.
AB  - Lipid droplets (LDs) are dynamic organelles that collect, store, and supply
      lipids [1]. LDs have a central role in the exchange of lipids occurring between
      the cell and the environment and provide cells with substrates for energy
      metabolism, membrane synthesis, and production of lipid-derived molecules such as
      lipoproteins or hormones. However, lipid-derived metabolites also cause
      progressive lipotoxicity [2], accumulation of reactive oxygen species (ROS),
      endoplasmic reticulum stress, mitochondrial malfunctioning, and cell death [2].
      Intracellular accumulation of LDs is a hallmark of prevalent human diseases,
      including obesity, steatosis, diabetes, myopathies, and arteriosclerosis [3].
      Indeed, nonalcoholic fatty liver disease is the most common cause of abnormal
      hepatic function among adults [4, 5]. Lipotoxicity gradually promotes cellular
      ballooning and disarray, megamitochondria, accumulation of Mallory's hyaline in
      hepatocytes, and inflammation, fibrosis, and cirrhosis in the liver. Here, using
      confocal microscopy, serial-block-face scanning electron microscopy, and flow
      cytometry, we show that LD accumulation is heterogeneous within a cell population
      and follows a positive skewed distribution. Lipid availability and fluctuations
      in biochemical networks controlling lipolysis, fatty acid oxidation, and protein
      synthesis contribute to cell-to-cell heterogeneity. Critically, this reversible
      variability generates a subpopulation of cells that effectively collect and store
      lipids. This high-lipid subpopulation accumulates more LDs and more ROS and
      reduces the risk of lipotoxicity to the population without impairing overall
      lipid homeostasis, since high-lipid cells can supply stored lipids to the other
      cells. In conclusion, we demonstrate fat storage compartmentalization within a
      cell population and propose that this is a protective social organization to
      reduce lipotoxicity. 

PMID- 23871245
TI  - Quantitation of gamma-hydroxybutyric acid in dried blood spots in newborn
      screening.

PMID- 23871244
TI  - A causal role for V5/MT neurons coding motion-disparity conjunctions in resolving
      perceptual ambiguity.
AB  - Judgments about the perceptual appearance of visual objects require the
      combination of multiple parameters, like location, direction, color, speed, and
      depth. Our understanding of perceptual judgments has been greatly informed by
      studies of ambiguous figures, which take on different appearances depending upon
      the brain state of the observer. Here we probe the neural mechanisms hypothesized
      as responsible for judging the apparent direction of rotation of ambiguous
      structure from motion (SFM) stimuli. Resolving the rotation direction of SFM
      cylinders requires the conjoint decoding of direction of motion and binocular
      depth signals [1, 2]. Within cortical visual area V5/MT of two macaque monkeys,
      we applied electrical stimulation at sites with consistent multiunit tuning to
      combinations of binocular depth and direction of motion, while the monkey made
      perceptual decisions about the rotation of SFM stimuli. For both ambiguous and
      unambiguous SFM figures, rotation judgments shifted as if we had added a specific
      conjunction of disparity and motion signals to the stimulus elements. This is the
      first causal demonstration that the activity of neurons in V5/MT contributes
      directly to the perception of SFM stimuli and by implication to decoding the
      specific conjunction of disparity and motion, the two different visual cues whose
      combination drives the perceptual judgment. 

PMID- 23871246
TI  - Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral
      obstruction in rats.
AB  - Hydrogen has been demonstrated to have effective protection against tissue
      injuries caused by oxidative stress, inflammation, and apoptosis. This study
      investigated the efficacy of hydrogen-rich saline (HS) on the prevention of renal
      injury induced by unilateral ureteric obstruction (UUO) in rats. Male Sprague
      Dawley rats were divided randomly into 4 groups: sham group, UUO group,
      UUO+saline group, and UUO+HS group. UUO was induced by ligation of the left
      ureter. 5ml/kg HRSS or saline was administered beginning 1day after UUO and for
      10days thereafter. Rats were killed at 10days after UUO. Left kidneys were
      excised immediately for the tissue histologic examinations and biochemical
      assays. Renal injury scores in the UUO group and the UUO+saline group were
      significantly higher compared with those in the sham group. However,
      administration of HS significantly reduced the injury score. Apoptosis index was
      significantly increased in UUO group and the UUO+saline group. HS treatment also
      reduced the apoptosis index. Interstitial fibrosis and macrophage infiltration
      were obvious in UUO kidneys. However, HS treatment significantly reduced the
      fibrosis and infiltration of macrophage in UUO kidneys. Significant increase in
      the MDA level and decrease in the SOD activity were observed in UUO group and the
      UUO+saline group. MDA level of UUO+HS group was significantly reduced. In
      addition, SOD activity of was significantly improved after treatment of HS. The
      data provide a biochemical and histologic basis for HS acting as a novel
      therapeutic strategy for preventing the renal injury induced by UUO. 

PMID- 23871247
TI  - Sodium nitroprusside (SNP) sensitizes human gastric cancer cells to TRAIL-induced
      apoptosis.
AB  - AIM: To investigate the effects of the nitrous oxide (NO)-donor sodium
      nitroprusside (SNP) on tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-mediated apoptosis in human gastric cancer cells. METHODS: The MTT assay
      and flow cytometry were used to detect cellular proliferation and markers of
      apoptosis, respectively. Expression levels of caspases-8, and 9 were determined
      by Western blot. Changes in Nitric Oxide Synthase (NOS) activity, NO production,
      and caspase activation were also evaluated. RESULTS: We found that TRAIL induced
      apoptosis and cell cycle arrest in human gastric cancer cell lines, and that this
      effect was mediated by NO production, and activation of both the extrinsic and
      intrinsic signaling pathways of apoptosis. In addition, we found that the NO
      donor SNP sensitizes gastric cancer cells to TRAIL-mediated apoptosis. Treatment
      of cells with both TRAIL and SNP resulted in increased activation of caspase-8
      and caspase-9 and NO release. Inhibition of caspase-8 blocked cell TRAIL-induced
      apoptosis, while a selective caspase-9 inhibitor was unable to prevent apoptosis
      induced by either TRAIL or TRAIL plus SNP. Inhibition of NOS could block the
      activation of caspase-9, but had no obvious effect on cell apoptosis.
      CONCLUSIONS: SNP-sensitized gastric cancer cells to TRAIL-induced cytotoxicity by
      stimulating the release of NO, in turn facilitating the mitochondria-mediated
      signal transduction pathway. The engagement of the mitochondria signaling
      pathways along with the TRAIL death receptor signaling pathway synergistically
      increase levels of apoptosis in these cells.

PMID- 23871248
TI  - Nation-wide data on screening performance during the transition to digital
      mammography: observations in 6 million screens.
AB  - PURPOSE: To critically evaluate and confirm previous results regarding the
      diagnostic accuracy of digital mammography screening (DM), compared to screen
      film mammography (SFM) in the whole Dutch screening programme, in the period of
      2004-2010, during which a full transition from SFM to DM was made. MATERIALS AND
      METHODS: 1.5 million DM and 4.6 million SFM were read in the Dutch national
      breast cancer screening programme in the period of 2004-2010. We evaluated recall
      rate, detection rate, positive predictive value and tumour-size distribution for
      younger and older women, for first time participants and women having a timely
      subsequent screen. We compared DM screens read by radiologists reading DM and SFM
      (DM-group) to SFM screens read by these radiologists (SFM-group) and to SFM
      screens read by radiologists reading only SFM (SFMonly-group). RESULTS: Recall
      rate was 2.0% (95% confidence interval (C.I.): 2.0; 2.1) in the DM-group,
      compared to 1.6% (95% C.I.: 1.6; 1.6) in the SFM-group and 1.6% (95% C.I.: 1.5;
      1.6) in the SFM only-group. The overall detection rates were 5.9/1000 screens
      (95% C.I.: 5.7; 6.0) in the DM-group, 5.1/1000 screens (95% C.I.: 5.0; 5.2) in
      the SFM-group and 5.0/1000 screens (95% C.I.: 5.0; 5.1) in the SFM only-group.
      Detection rate rose most markedly in younger women (age 49-54) from 4.0/1000
      screens to 5.1/1000 screens (p-value<0.001). Positive predictive value (PPV) in
      DM rose from 18.4% (95% C.I.: 14.6; 23.1) in 2004 to 32.5% (95% C.I.: 31.7; 33.2)
      in 2010. Detection rate rose in SFM-group from 5.0/1000 screens (95% C.I.: 4.7;
      5.3) in 2004 to 5.5/1000 screens (95% C.I.: 5.2; 5.7) in 2010. Detection rate in
      DM-group rose mostly due to ductal carcinoma in situ (DCIS) detection especially
      in younger women/first screens. The proportion of T1a tumours was significantly
      higher in DM-group; otherwise size distribution did not change significantly for
      invasive carcinoma. Recall rates were variable between different screening
      regions. CONCLUSION: In accordance to previous, smaller, studies, we can confirm
      that DM has a higher detection rate compared to SFM, at the cost of a higher
      recall rate and lower PPV. More DCIS and a higher fraction of very small tumours
      were detected with DM, which has positive consequences for the stage shift as a
      result of mass screening.

PMID- 23871249
TI  - Accumulation and distribution of (137)Cs and (90)Sr in the body of the wild boar
      (Sus scrofa) found on the territory with radioactive contamination.
AB  - We studied the concentration and distribution of (137)Cs and (90)Sr in the bodies
      of 188 wild boar (Sus scrofa Linnaeus, 1758) taken near the Chernobyl site. Of
      these, 111 animals were taken in the Alienation Zone, 41 animals were taken in
      the Permanent Control Zone and 36 animals were taken in the Periodic Control
      Zone. The samples included muscle and bone (rib) tissues and samples of heart,
      liver, lungs, kidneys, spleen, genitals and skin. The weight of the samples was
      0.5 kg fresh weigh. The average concentration of (137)Cs in the muscles of the
      wild boar found in the Alienation Zone was 46 +/- 10 kBq/kg, in the Permanent
      Control Zone - 13 +/- 3.0 kBq/kg and in the Periodic Control Zone - 0.6 +/- 0.1
      kBq/kg. The largest concentration of (137)Cs was detected in the muscle tissue
      and kidneys taken animals. In some samples of muscle tissue it reached more than
      660 kBq/kg. The (137)Cs concentrations were also high in heart and spleen up 64.3
      kBq/kg and 67.5 kBq/kg - animals from the Alienation Zone and 10.3-10.6 kBq/kg -
      animals from the Permanent Control zone. The lowest concentration of (137)Cs was
      found in the lungs and skin of animals. The analyses of (90)Sr concentration in
      the organs and tissues of the wild boar showed that (90)Sr was concentrated
      mainly in the bone tissue. The average level of (90)Sr concentration in bone was
      17.6 kBq/kg fresh weight animals from the Alienation Zone and 13.47 kBg/kg -
      animals from the Permanent Control zone. In muscle tissues and organs contained
      (90)Sr - 30.0-110.0 Bq/kg in the Alienation Zone and 11.0-30.0 Bq/kg in the
      Permanent Control zone. 

PMID- 23871250
TI  - Biological availability of (238)U, (234)U and (226)Ra for wild berries and meadow
      grasses in natural ecosystems of Belarus.
AB  - This work is devoted to investigation of behavior of (234)U, (238)U and (226)Ra
      by determining the soil to plant transfer under different natural conditions such
      as forest or swamped areas and meadow lands with different soil types. The paper
      summarizes the data on investigation of uranium and radium uptake by wild berries
      and natural meadow grasses in the typical conditions of Belarus. Parameters
      characterizing the biological availability of (234)U, (238)U and (226)Ra for
      bilberry (Vaccinium myrtillus), lingonberry (Vaccinium viti-idaea), blueberry
      (Vaccinium iliginosum) and cranberry (Vaccinium oxycoccus palustris) as well as
      for widely occurring mixed meadow vegetation, which belongs to the sedge-grass or
      grass-sedge associations and forbs, have been established. In the sites under
      investigation, the deposition levels of (238+239+240)Pu were less than 0.37 kBq
      m(-2) and (137)Cs deposition ranged between less than 0.37 and 37 kBq m(-2). It
      was found that activity concentrations of radionuclides in berries varied in the
      ranges of 0.037-0.11 for (234)U, 0.036-0.10 for (238)U and 0.11-0.43 Bq kg(-1)
      for (226)Ra, but in the mixed meadow grasses they were 0.32-4.4, 0.24-3.9 and
      0.14-6.9 Bq kg(-1) accordingly. The (234)U/(238)U activity ratios were 1.02 +/-
      0.01 for wild berries, 1.20 +/- 0.09 for underground meadow grasses and 1.02 +/-
      0.02 for proper soils. The concentration ratios (CRs, dry weight basis) of (234)U
      and (238)U for mixed meadow grasses were 0.036-0.42 and 0.041-0.46 respectively.
      The correspondent geometric means (GM) were 0.13 and 0.15 with geometric standard
      deviations (GSD) of 2.4. The CRs of (226)Ra for meadow grasses were 0.031-1.0
      with GM 0.20 and GSD 2.6. The CRs of (234)U, (238)U and (226)Ra for wild berries
      ranged within 0.0018-0.008 (GM is 0.0034, GSD is 1.8), 0.0018-0.008 (GM is
      0.0035, GSD is 1.8) and 0.005-0.033 (GM is 0.016, GSD is 2.1) accordingly. The
      highest CR values of uranium for mixed meadow grasses were found in the sites
      with high-moor peat and sandy soils. The lowest CRs for grasses were common to
      loamy and peat-gley soils. The CRs for the same berry species in the sites with
      sandy soils exceeded the appropriate CR values in the sites with loamy soils by
      factors of 3-4 for uranium and 4-6 for radium. The data obtained on radionuclide
      accumulation by plants were used to estimate the average annual effective doses
      to the population from radionuclide intake through the "soil - wild berries -
      man" and "soil - meadow vegetation - animal - cow milk-beef - man" trophic
      chains. The effective doses resulting from (234)U, (238)U and (226)Ra intake with
      the wild berries for adults were estimated as 0.02-0.09 MUSv y(-1) (GM is 0.044,
      GSD is 1.6). It was established that only in the territory with (137)Cs
      deposition of ~1.0-1.5 kBq m(-2) the doses resulting from (234)U, (238)U and
      (226)Ra intake with wild berries can be comparable with corresponding doses from
      (137)Cs. In the territories with higher levels of (137)Cs deposition the doses
      resulting from its intake with the wild berries are usually over the summarized
      doses of uranium and (226)Ra. The total doses for adults resulting from uranium
      and (226)Ra intake with cow milk and beef ranged between 0.2 and 7.2 MUSv y(-1)
      (GM is 2.0; GSD is 2.9) and the doses from (226)Ra usually exceeded the
      appropriate doses of uranium with a factor of 3-37. In the sites with (137)Cs
      deposition less than 3.7 kBq m(-2), the doses from (234)U, (238)U and (226)Ra
      intake with cow milk and beef were assessing as 1.1-7.2 MUSv y(-1) and they were
      usually higher than the doses from (137)Cs, which were assessing as 0.4-3.2 MUSv
      y(-1) for its deposition 2 kBq m(-2). In the territory with (137)Cs deposition 10
      20 kBq m(-2) and higher, the internal doses resulting from (137)Cs intake with
      cow milk and beef (10-50 MUSv y(-1)) exceeded the proper doses from natural
      (234)U, (238)U and (226)Ra. 

PMID- 23871251
TI  - Agreement in interpreting villous elements and dysplasia in adenomas less than
      one centimetre in size.
AB  - BACKGROUND: Villous elements and dysplasia grade in small adenomas are used in
      many countries to guide post-polypectomy colonoscopy intervals. AIMS: Measure
      agreement in interpretation of villous elements and dysplasia in small adenomas.
      METHODS: Consecutive endoscopically resected adenomas <10mm in size (203 adenomas
      less than 6mm and 149 adenomas 6-9 mm in size) were reviewed by 3 expert
      gastrointestinal pathologists. Interpretations were compared to routine clinical
      pathology readings at our institution and to each other. RESULTS: All
      pathologists used the same definitions for villous and tubular histology. The
      overall kappas for villous elements in <6mm and 6-9 mm adenomas were 0.29 and
      0.26, respectively. Interpretation of dysplasia grade had kappas of 0.02 and 0.09
      for adenomas <6mm and 6-9 mm, respectively. Two expert pathologists who used
      cytologic criteria had much higher fractions of high grade dysplasia compared to
      the third expert and the pathologists at our centre, who relied on architectural
      criteria. CONCLUSIONS: Villous elements and dysplasia grade in small adenomas are
      problematic as determinants of post-polypectomy surveillance intervals. Uniform
      pathologic criteria for dysplasia grade are needed.

PMID- 23871252
TI  - Characterization of fecal concentrations in human and other animal sources by
      physical, culture-based, and quantitative real-time PCR methods.
AB  - The characteristics of fecal sources, and the ways in which they are measured,
      can profoundly influence the interpretation of which sources are contaminating a
      body of water. Although feces from various hosts are known to differ in mass and
      composition, it is not well understood how those differences compare across fecal
      sources and how differences depend on characterization methods. This study
      investigated how nine different fecal characterization methods provide different
      measures of fecal concentration in water, and how results varied across twelve
      different fecal pollution sources. Sources investigated included chicken, cow,
      deer, dog, goose, gull, horse, human, pig, pigeon, septage and sewage. A
      composite fecal slurry was prepared for each source by mixing feces from 6 to 22
      individual samples with artificial freshwater. Fecal concentrations were
      estimated by physical (wet fecal mass added and total DNA mass extracted),
      culture-based (Escherichia coli and enterococci by membrane filtration and
      defined substrate), and quantitative real-time PCR (Bacteroidales, E. coli, and
      enterococci) characterization methods. The characteristics of each composite
      fecal slurry and the relationships between physical, culture-based and qPCR-based
      characteristics varied within and among different fecal sources. An in silico
      exercise was performed to assess how different characterization methods can
      impact identification of the dominant fecal pollution source in a mixed source
      sample. A comparison of simulated 10:90 mixtures based on enterococci by defined
      substrate predicted a source reversal in 27% of all possible combinations, while
      mixtures based on E. coli membrane filtration resulted in a reversal 29% of the
      time. This potential for disagreement in minor or dominant source identification
      based on different methods of measurement represents an important challenge for
      water quality managers and researchers. 

PMID- 23871253
TI  - Influence of thermophilic aerobic digestion as a sludge pre-treatment and solids
      retention time of mesophilic anaerobic digestion on the methane production,
      sludge digestion and microbial communities in a sequential digestion process.
AB  - In this study, the changes in sludge reduction, methane production and microbial
      community structures in a process involving two-stage thermophilic aerobic
      digestion (TAD) and mesophilic anaerobic digestion (MAD) under different solid
      retention times (SRTs) between 10 and 40 days were investigated. The TAD reactor
      (RTAD) was operated with a 1-day SRT and the MAD reactor (RMAD) was operated at
      three different SRTs: 39, 19 and 9 days. For a comparison, control MAD (RCONTROL)
      was operated at three different SRTs of 40, 20 and 10 days. Our results reveal
      that the sequential TAD-MAD process has about 42% higher methane production rate
      (MPR) and 15% higher TCOD removal than those of RCONTROL when the SRT decreased
      from 40 to 20 days. Denaturing gradient gel electrophoresis (DGGE) and real-time
      PCR results indicate that RMAD maintained a more diverse bacteria and archaea
      population compared to RCONTROL, due to the application of the biological TAD pre
      treatment process. In RTAD, Ureibacillus thermophiles and Bacterium thermus were
      the major contributors to the increase in soluble organic matter. In contrast,
      Methanosaeta concilii, a strictly aceticlastic methanogen, showed the highest
      population during the operation of overall SRTs in RMAD. Interestingly, as the
      SRT decreased to 20 days, syntrophic VFA oxidizing bacteria, Clostridium
      ultunense sp., and a hydrogenotrophic methanogen, Methanobacterium beijingense
      were detected in RMAD and RCONTROL. Meanwhile, the proportion of archaea to total
      microbe in RMAD and RCONTROL shows highest values of 10.5 and 6.5% at 20-d SRT
      operation, respectively. Collectively, these results demonstrate that the
      increased COD removal and methane production at different SRTs in RMAD might be
      attributed to the increased synergism among microbial species by improving the
      hydrolysis of the rate limiting step in sludge with the help of the biological
      TAD pre-treatment.

PMID- 23871254
TI  - Strategies for the recovery of nutrients and metals from anaerobically digested
      dairy farm sludge using cross-flow microfiltration.
AB  - This work reports on the recovery of nutrients and metals from anaerobically
      digested manure sludge using a pilot scale microfiltration membrane system.
      Soluble nitrogen (N), phosphorous (P) and metals are valuable commodities which
      exist in high concentration in anaerobically digested manure sludge. The typical
      disposal of sludge on farmland can cause serious harm to the ecosystem due to
      eutrophication. The recovery of these materials in clarified solutions represents
      an added value product and a less contaminated sludge that is environmentally
      less hazardous. The objective of this study was to investigate the recovery of
      nutrients and metals using a pilot scale cross-flow membrane filtration system. A
      ceramic membrane of 0.22 m(2) and 0.2 MUm pore size was used to perform solid
      liquid separations and soluble materials were recovered in particle and bacteria
      free solutions. Strategies such as batch diafiltration (DF) and acid pre
      treatment were investigated and the fractions collected compared against the
      initial permeate containing 686.2 mg NH3-N L(-1) and 41.51 mg PO4-P L(-1).
      Clarified fractions obtained through DF with no acid pre-treatment yielded N:P
      ratios of around 30 and relatively low levels of P (364.24 mg NH3-N L(-1) and
      25.60 mg PO4-P L(-1)) and metals. Acid pre-treatment of the sludge resulted in a
      two-fold increase of P extracted (271.11 mg NH3-N L(-1) and 71.60 mg PO4-P L(
      1)), altering N:P ratios to 8. Depending on the metal species, a 2-9 fold
      increase in concentration was also observed. Thus it has been demonstrated that
      different treatment strategies influence the removal and recovery of nutrients
      and metals from sludge. The best treatment conditions therefore depend on the
      targeted materials to be recovered. By careful manipulation of the treatment
      processes the production of specific nutrient compositions in terms of N:P ratios
      is possible.

PMID- 23871255
TI  - In-situ identification of iron electrocoagulation speciation and application for
      natural organic matter (NOM) removal.
AB  - In this work, iron speciation in electrocoagulation (EC) was studied to determine
      the impact of operating parameters on natural organic matter (NOM) removal from
      natural water. Two electrochemical EC parameters, current density (i) and charge
      loading rate (CLR), were investigated. Variation of these parameters led to a
      near unity current efficiency (phi = 0.957 +/- 0.03), at any combination of i in
      a range of 1-25 mA/cm(2) and CLR in a range of 12-300 C/L/min. Higher i and CLR
      led to a higher bulk pH and limited the amount of dissolved oxygen (DO) reduced
      at the cathode surface due to mass transfer limitations. A low i (1 mA/cm(2)) and
      intermediate CLR (60 C/L/min) resulted in low bulk DO (<2.5 mg/L), where green
      rust (GR) was identified by in-situ Raman spectroscopy as the primary crystalline
      electrochemical product. Longer electrolysis times at higher i led to magnetite
      (Fe3O4) formation. Both higher (300 C/L/min) and lower (12 C/L/min) CLR values
      led to increased DO and/or increased pH, with lepidocrocite (gamma-FeOOH) as the
      only crystalline species observed. The NOM removal of the three identified
      species was compared, with conditions leading to GR formation showing the
      greatest dissolved organic carbon removal, and highest removal of the low
      apparent molecular weight (<550 Da) chromophoric NOM fraction, determined by high
      performance size exclusion chromatography.

PMID- 23871256
TI  - Comparison of PCR and quantitative real-time PCR methods for the characterization
      of ruminant and cattle fecal pollution sources.
AB  - The State of California has mandated the preparation of a guidance document on
      the application of fecal source identification methods for recreational water
      quality management. California contains the fifth highest population of cattle in
      the United States, making the inclusion of cow-associated methods a logical
      choice. Because the performance of these methods has been shown to change based
      on geography and/or local animal feeding practices, laboratory comparisons are
      needed to determine which assays are best suited for implementation. We describe
      the performance characterization of two end-point PCR assays (CF128 and CF193)
      and five real-time quantitative PCR (qPCR) assays (Rum2Bac, BacR, BacCow, CowM2,
      and CowM3) reported to be associated with either ruminant or cattle feces. Each
      assay was tested against a blinded set of 38 reference challenge filters (19
      duplicate samples) containing fecal pollution from 12 different sources suspected
      to impact water quality. The abundance of each host-associated genetic marker was
      measured for qPCR-based assays in both target and non-target animals and compared
      to quantities of total DNA mass, wet mass of fecal material, as well as
      Bacteroidales, and enterococci determined by 16S rRNA qPCR and culture-based
      approaches (enterococci only). Ruminant- and cow-associated genetic markers were
      detected in all filters containing a cattle fecal source. However, some assays
      cross-reacted with non-target pollution sources. A large amount of variability
      was evident across laboratories when protocols were not fixed suggesting that
      protocol standardization will be necessary for widespread implementation.
      Finally, performance metrics indicate that the cattle-associated CowM2 qPCR
      method combined with either the BacR or Rum2Bac ruminant-associated methods are
      most suitable for implementation. 

PMID- 23871257
TI  - Norovirus and MS2 inactivation kinetics of UV-A and UV-B with and without TiO2.
AB  - Germicidal ultraviolet, such as 254-nm UV-C, is a common method of disinfection
      of pathogenic enteric viruses. However, the disinfection efficacies of UV-A or -B
      in terms of inactivating waterborne viruses such as norovirus have not been
      characterized. We evaluated the inactivation kinetics of MS2 bacteriophage and
      murine norovirus (MNV), a surrogate of human norovirus (NoV), by UV-A and -B. In
      addition to UV disinfection, we further investigated whether the presence of TiO2
      could enhance the virus inactivation kinetics of UV-A and -B. Both MS2 and MNV
      were highly resistant to UV-A. However, the addition of TiO2 enhanced the
      efficacy of UV-A for inactivating these viruses. UV-A dose of 1379 mJ/cm(2)
      resulted in a 4 log10 reduction. In comparison, UV-B alone effectively
      inactivated both MS2 and MNV, as evidenced by the 4 log10 reduction by 367
      mJ/cm(2) of UV-B. The addition of TiO2 increased the inactivation of MS2;
      however, it did not significantly increase the efficacy of UV-B disinfection for
      inactivating MNV. When these treatments were applied to field water such as
      groundwater, the results were generally consistent with the laboratory findings.
      Our results clearly indicated that UV-B is useful for the disinfection of
      waterborne norovirus. However, MNV was quite resistant to UV-A, and UV-A
      effectively inactivated the tested viruses only when used in combination with
      TiO2.

PMID- 23871258
TI  - Characterization of effluent water qualities from satellite membrane bioreactor
      facilities.
AB  - Membrane bioreactors (MBRs) are often a preferred treatment technology for
      satellite water recycling facilities since they produce consistent effluent water
      quality with a small footprint and require little or no supervision. While the
      water quality produced from centralized MBRs has been widely reported, there is
      no study in the literature addressing the effluent quality from a broad range of
      satellite facilities. Thus, a study was conducted to characterize effluent water
      qualities produced by satellite MBRs with respect to organic, inorganic, physical
      and microbial parameters. Results from sampling 38 satellite MBR facilities
      across the U.S. demonstrated that 90% of these facilities produced nitrified (NH4
      N <0.4 mg/L-N) effluents that have low organic carbon (TOC <8.1 mg/L),
      turbidities of <0.7 NTU, total coliform bacterial concentrations <100 CFU/100 mL
      and indigenous MS-2 bacteriophage concentrations <21 PFU/100 mL. Multiple
      sampling events from selected satellite facilities demonstrated process
      capability to consistently produce effluent with low concentrations of ammonia,
      TOC and turbidity. UV-254 transmittance values varied substantially during
      multiple sampling events indicating a need for attention in designing downstream
      UV disinfection systems. Although enteroviruses, rotaviruses and hepatitis A
      viruses (HAV) were absent in all samples, adenoviruses were detected in effluents
      of all nine MBR facilities sampled. The presence of Giardia cysts in filtrate
      samples of two of nine MBR facilities sampled demonstrated the need for an
      appropriate disinfection process at these facilities.

PMID- 23871259
TI  - A multicenter evaluation of oral pressure therapy for the treatment of
      obstructive sleep apnea.
AB  - OBJECTIVE: We aimed to evaluate the impact of a novel noninvasive oral pressure
      therapy (OPT) (Winx(r), ApniCure) system on polysomnographic measures of sleep
      disordered breathing, sleep architecture, and sleep stability in obstructive
      sleep apnea (OSA). SUBJECTS AND METHODS: A 4-week, multicenter, prospective, open
      label, randomized, crossover, first-night order of control vs treatment, single
      arm trial was conducted in five American Academy of Sleep Medicine (AASM) -
      accredited sleep clinics and one research laboratory. Sixty-three subjects
      (analysis cohort) were studied from a screening cohort of 367 subjects. The
      analysis cohort was 69.8% men, ages 53.6+/-8.9 years (mean+/-SD), body mass index
      of 32.3+/-4.5kg/m(2), with mild to severe OSA. At treatment initiation, subjects
      received random assignment to one night with and one without (control) treatment,
      and they were assessed again following 28 nights of treatment. Breathing and
      sleep architecture were assessed each night based on blind scoring by a single
      centralized scorer using AASM criteria. RESULTS: Average nightly usage across the
      take-home period was 6.0+/-1.4h. There were no severe or serious device-related
      adverse events (AEs). Median apnea-hypopnea index (AHI) was 27.5 events per hour
      on the control night, 13.4 events per hour on the first treatment night, and 14.8
      events per hour after 28days of treatment. A clinically significant response
      (treatment AHI ?10/h and ?50% of control values) was seen in 20 of the 63
      subjects evaluated. Rapid eye movement percentage (REM%) was significantly
      increased, and N1%, stage shifts to N1 sleep, overall stage shifts, total
      awakenings, and arousals per hour were all significantly reduced at both
      treatment nights compared to controls. Mean Epworth sleepiness scale (ESS) was
      significantly reduced from 12.1 to 8.6 (Cohen d effect size, 0.68) in those
      untreated for two or more weeks prior to OPT study participation and remained
      unchanged in subjects who directly switched from continuous positive airway
      pressure (CPAP) therapy to OPT. CONCLUSION: Clinically significant improvements
      in sleep quality and continuity, AHI, ODI, ESS, and overall clinical status were
      achieved in an easily identified subgroup. OPT was safe and well-tolerated and
      nightly usage was high.

PMID- 23871260
TI  - Predictors of improvement in subjective sleep quality reported by older adults
      following group-based cognitive behavior therapy for sleep maintenance and early
      morning awakening insomnia.
AB  - OBJECTIVE: Cognitive behavior therapy is an effective nonpharmacologic treatment
      for insomnia. However, individualized administration is costly and often results
      in substantial variability in treatment response across individual patients,
      particularly so for older adults. Group-based administration has demonstrated
      impressive potential for a brief and inexpensive answer to the effective
      treatment of insomnia in the older population. It is important to identify
      potential predictors of response to such a treatment format to guide clinicians
      when selecting the most suitable treatment for their patients. The aim of our
      study was to identify factors that predict subjective sleep quality of older
      adults following group-based administration of cognitive behavior therapy for
      insomnia (CBT-I). METHODS: Eighty-six adults (41 men; mean age, 64.10 y; standard
      deviation [SD], 6.80) with sleep maintenance or early morning awakening insomnia
      were selected from a community-based sample to participate in a 4-week group
      based treatment program of CBT-I. Participants were required to complete 7-day
      sleep diaries and a comprehensive battery of questionnaires related to sleep
      quality and daytime functioning. Hierarchical multiple regression analyses were
      used to identify factors predicting subjective sleep quality immediately
      following treatment and at 3-month follow-up. Sleep diaries reported average
      nightly sleep efficiency (SE), which was used as the outcome measure of sleep
      quality. RESULTS AND CONCLUSIONS: Participants with the greatest SE following
      treatment while controlling for pretreatment SE were relatively younger and had
      more confidence in their ability to sleep at pretreatment. These characteristics
      may be useful to guide clinicians when considering the use of a group-based CBT-I
      for sleep maintenance or early morning awakening insomnia in older adults.

PMID- 23871262
TI  - Conservatorship: a nursing practice concern.

PMID- 23871261
TI  - Biologically inspired strategies for combating bacterial biofilms.
AB  - Infections caused by bacterial biofilms are a significant global health problem,
      causing considerable patient morbidity and mortality and contributing to the
      economic burden of infectious disease. This review describes diverse strategies
      to combat bacterial biofilms, focusing firstly on small molecule interference
      with bacterial communication and signaling pathways, including quorum sensing and
      two-component signal transduction systems. Secondly we discuss enzymatic
      approaches to the degradation of extracellular matrix components to effect
      biofilm dispersal. Both of these approaches are based upon non-microbicidal
      mechanisms of action, and thereby do not place a direct evolutionary pressure on
      the bacteria to develop resistance. Such approaches have the potential to, in
      combination with conventional antibiotics, play an important role in the
      eradication of biofilm based bacterial infections. 

PMID- 23871263
TI  - Caregivers' psychosocial factors underlying sugar-sweetened beverage intake among
      non-Hispanic black preschoolers: an elicitation study.
AB  - The purpose of this study was to explore caregivers' beliefs and perceptions
      regarding serving sugar-sweetened beverages (SSBs) to non-Hispanic black
      preschoolers. The Theory of Planned Behavior (TpB) was used as the framework for
      conducting elicitation interviews among a sample of (n = 19) caregivers. Thematic
      coding of interview transcripts revealed that the decision to serve SSBs to
      preschoolers is driven by numerous individual, familial, cultural, and
      environmental factors. Salient factors associated with serving SSBs included
      convenience, cost, taste, potential health consequences, availability, and
      pressure from other parents. Population-specific interventions aimed at reducing
      SSB intake among non-Hispanic preschoolers are discussed.

PMID- 23871264
TI  - The source of cognitive complaints predicts diagnostic conversion differentially
      among nondemented older adults.
AB  - OBJECTIVE: The objective of this study was to compare whether different sources
      of cognitive complaint (i.e., subjective and informant) predict diagnostic
      conversion in nondemented older adults. METHODS: Participants from the National
      Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC;
      n = 4414; mean age, 73 +/- 8 years; 69% female) or mild cognitive impairment
      (MCI; n = 1843; mean age, 74 +/- 8 years; 52% female). Multinomial logistic
      regression related baseline cognitive complaint (no complaint, self only,
      informant only, or both self and informant) to diagnostic outcome (reversion,
      stable, or conversion). RESULTS: At follow-up, 14% of NC participants converted
      to MCI/dementia (3.5 +/- 1.8 years), and 41% of MCI participants converted to
      dementia (3.0 +/- 1.6 years). Among NC participants, self complaint only (odds
      ratio [OR], 2.1; 99% confidence interval (CI),1.5-2.9; P < .001), informant
      complaint only (OR, 2.2; 99% CI, 1.2-3.9; P < .001), and both self and informant
      complaint (OR, 4.2; 99% CI, 2.9-6.0; P < .001) were associated with diagnostic
      conversion compared with no complaint. Among participants with MCI-compared with
      no complaint, informant complaint only (OR, 2.2; 99% CI, 1.2-4.3, P = .002), and
      both self and informant complaint (OR, 2.9; 99% CI, 1.8-4.8; P < .001)-were
      associated with conversion. CONCLUSIONS: Cognitive complaints are related to
      conversion among nondemented older adults. Complaint from both (i.e. mutual
      complaint) sources was most predictive of diagnostic outcome, followed by
      informant complaint, highlighting the need for obtaining informant corroboration
      to enhance prognosis and distinguish underlying pathological processes from
      normal cognitive aging. Self complaint was related inconsistently to diagnostic
      outcome.

PMID- 23871265
TI  - Effects of post-partum administration of ketoprofen on sow health and piglet
      growth.
AB  - The effect of the non-steroidal anti-inflammatory drug ketoprofen on the post
      farrowing phase of sows was studied in a randomized, blinded, placebo-controlled
      trial. Ketoprofen (3mg/kg) was administered intramuscularly to 20 healthy sows
      for 3 days post-partum (p.p.). The control group (n=20) received a saline
      placebo. Backfat, number of days of constipation and days before feed refusal
      were measured. Body condition (BCS) and shoulder sores were scored for 1 week
      p.p. Changes in BCS, backfat and shoulder sore scores were analysed with ANOVA.
      Blood was collected on days -1, 0, 5 and 14 with respect to medication. Aspartate
      aminotransferase (AST), creatinine kinase (CK), haptoglobin and serum amyloid A
      (SAA) were quantified and analysed with a Mann-Whitney U test. BCS and backfat
      decreased less following ketoprofen administration than with the placebo (-0.08
      +/- 0.2 vs. -0.8 +/- 0.2, 1.0 +/- 0.8mm vs. -2.0 +/- 0.9 mm, respectively; P<0.05
      for both) during the first 2 weeks of lactation. The shoulder sore score
      deterioration was milder during days 4-6 p.p. with ketoprofen than placebo
      (P<0.05). Duration of constipation was shorter with ketoprofen than placebo (5.5
      +/- 0.3 vs. 6.4 +/- 0.3 days p.p.; P<0.05). Incidences of feed refusal occurred
      later in the ketoprofen group than in the placebos (9.6 +/- 0.9 vs. 3.8 +/- 0.8
      days p.p.; P<0.05). AST and SAA values were higher after ketoprofen
      administration than placebo on day 5 p.p. (P<0.05). It was concluded that
      ketoprofen appeared to benefit sows during the first 2 weeks post farrowing, but
      caused some tissue irritation.

PMID- 23871266
TI  - Detection of Cryptosporidium oocysts in fresh calf faeces: characteristics of two
      simple tests and evaluation of a semi-quantitative approach.
AB  - The objective of the present study was to evaluate the characteristics of two
      rapid tests, namely, a faecal smear staining method (Heine staining) and a
      commercially available immunochromatographic (IC) assay, against a direct
      immunofluorescent antibody test (IFAT) for the diagnosis of Cryptosporidium
      infections in 917 faecal samples from calves aged <3 weeks. These rapid tests
      were performed on non-concentrated faeces using a semi-quantitative approach
      using a 6-point scale (0-5) for Heine staining according to the number of oocysts
      per microscopic field, and a 4-point scale (0-3) for the IC assay reflecting the
      intensity of the positive line compared to the control line. Direct IFAT was
      performed following a diethyl ether concentration and results were expressed as
      oocysts per g of faeces (opg). Heine staining showed a sensitivity of 76.7% and a
      specificity of 90.7%. For faecal samples with >= 10,000opg, sensitivity increased
      to 90.0%. The sensitivity of the IC assay was lower (61.8%) but the specificity
      was 100%. For faeces with >= 100,000opg, the sensitivity of the IC assay reached
      81%, indicating some limitation for clinical cryptosporidiosis diagnosis.
      Additional scoring (1-5) of the Heine staining correlated with the corresponding
      direct IFAT results, particularly for ranges of 1000 to >1,000,000opg. Additional
      scoring from 1 to 3 according to the thickness of the sample line for the IC test
      correlated with increasing levels of Cryptosporidium opg measured by IFAT in the
      range of 10,000 to >1,000,000opg. In conclusion, both Heine staining and the IC
      test can be reliably used through a simple semi-quantitative scale for grossly
      quantifying oocyst output in calf faecal samples.

PMID- 23871267
TI  - Relation of osteoprotegerin in severe aortic valve stenosis to postoperative
      outcome and left ventricular function.
AB  - Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor
      superfamily and is known to be among the mediators of the calcification process
      that has been shown to increase in patients with aortic stenosis (AS). The aim of
      this study was to characterize the association of OPG with left ventricular (LV)
      function and remodeling and to evaluate the significance of preoperative OPG on
      long-term outcome in terms of survival and symptomatic improvement in 124
      patients with severe AS scheduled for aortic valve replacement (AVR). Patients
      were divided according to tertiles of preoperative OPG. Preoperative OPG was
      associated with age, EuroSCORE, and preoperative functional capacity. Despite
      similar ejection fraction and diastolic function among groups, longitudinal LV
      systolic function consistently decreased and markers of filling pressure
      increased across groups. During median follow-up of 4 years, 41 patients died of
      a presumed cardiovascular cause or remained in New York Heart Association
      functional class III or IV. The risk of a poor postoperative outcome after AVR
      increased with increasing OPG tertiles (15% vs 33% vs 51%, p = 0.002). In a
      multivariate model containing age, ejection fraction, N-terminal pro-brain
      natriuretic peptide and left atrial volume index, OPG was still significantly
      associated with postoperative outcome. In addition, OPG levels associated with
      cardiovascular mortality during follow-up. In conclusion, OPG is associated with
      LV and left atrial remodeling in patients with symptomatic severe AS undergoing
      AVR. Moreover, plasma OPG is associated with long-term postoperative outcome and
      may identify patients with poor symptomatic improvement after surgery.

PMID- 23871268
TI  - Aortic root dimensions and stiffness in healthy subjects.
AB  - The aim of the present study was to investigate the full range of aortic root
      diameters and stiffness in a group of subjects without known cardiovascular risk
      factors and/or overt cardiovascular disease. Four hundred and twenty-two healthy
      subjects (mean age 44.35 +/- 16.91 years, range 16 to 90, 284 men [67%])
      underwent comprehensive transthoracic echocardiography. The leading edge method
      was used for the end-diastolic aortic root diameters measured at 4 locations (1)
      the aortic annulus, (2) the sinuses of Valsalva, (3) the sinotubular junction,
      and (4) the maximum diameter of the proximal ascending aorta. Aortic wall
      stiffness was assessed using 2-dimensional guided M-mode evaluation of systolic
      and diastolic aortic diameter, 3 cm above the aortic valve. The absolute aortic
      root diameters increased with age in both genders. Aortic measurements were
      significantly greater in men than in women at all levels, whereas body surface
      area-indexed values were similar in men and women, except for the ascending aorta
      for which women tended to have greater values. Multivariable regression analysis
      using age and body size (weight, height, and body surface area) predicted all
      aortic diameters, whereas blood pressure indexes predicted only the distal part
      of the aorta. Aortic stiffness increased with age in men and women with no
      differences between genders; only age predicted aortic stiffness. The increment
      in aortic diameter with age was lesser when adjusted for aortic stiffness. In
      conclusion, we define the physiologic range of aortic root diameters and related
      stiffness in healthy subjects stratified by age and gender. Moreover, aortic
      stiffness should also be taken into account when the increase of aortic diameter
      is considered. 

PMID- 23871269
TI  - 1,25(OH)2D3 and specific IgE levels in children with recurrent tonsillitis, and
      allergic rhinitis.
AB  - OBJECTIVES: We investigated 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and specific
      immunoglobulin E (IgE) levels in children with recurrent tonsillitis (RT) plus
      allergic rhinitis (AR). METHODS: Thirty children with RT+AR were included in the
      study group, and 30 healthy children comprised the control group. AR-related
      symptoms were determined using a symptom scale. 1,25(OH)2D3 and specific IgE
      measurements were made in both groups. RESULTS: The 1,25(OH)2D3 value was
      significantly lower in the RT+AR group than in the control group. Specific IgE
      (mixed) panels were in normal limits in both groups; whereas specific IgE (mixed)
      grass pollen panel value of RT+AT group was significantly higher than that of the
      control group. Higher nasal itching, nasal obstruction, and concha edema scores
      were related to significantly higher specific IgE values for the (mixed) grass
      pollen panel, whereas higher sneeze scores were related to higher specific IgE
      values for the (mixed) pediatric panel. CONCLUSIONS: Children with grass pollen
      allergy may not be exposed to sufficient sunlight. With reduced 1,25(OH)2D3, T
      helper cells may increase, and allergic response also increases. As allergic
      events increased, these children did not go outside and thus lacked sun exposure.
      This vicious cycle must be broken, and children with RT+AR should have sunlight
      exposure to increase 1,25(OH)2D3 levels.

PMID- 23871270
TI  - Clinicians and laypeople assessment of facial attractiveness in patients with
      cleft lip and palate treated with LeFort I surgery or late maxillary protraction.
AB  - OBJECTIVE: To assess the changes in the facial attractiveness (FA) in two groups
      of cleft lip and palate patients with Class III malocclusions treated using
      LeFort I surgery or late maxillary protraction. MATERIALS AND METHODS:
      Standardized pre- and post-treatment photographs were taken of 32 patients (17
      corrected by orthognathic surgery and 17 by late maxillary protraction). The
      photographs were randomized and 42 clinicians and 121 laypeople rated them on a
      10-point FA scale via a web-based survey. RESULTS: Clinicians' mean FA values
      increased from 4.45 to 5.16 [95% CI of mean difference (MD), 0.59-0.82, p<0.001]
      in surgical cases and 4.84 to 5.30 (95% CI of MD, 0.35-0.56, p<0.001) in
      protraction cases. The laypeople mean FA values increased from 5.07 to 5.54 (95%
      CI of MD, 0.40-0.53, p<0.001) in surgical cases and 5.51 to 5.68 (95% CI of MD,
      0.11-0.23, p<0.001) in protraction cases. When patients combined, laypeople rated
      FA 0.64 points higher (95% CI, 0.54-0.74, p<0.001) in pre-treatment and 0.38
      points higher (95% CI, 0.27-0.48, p<0.05) in post-treatment relative to
      clinicians. CONCLUSION: Both clinicians and laypeople perceived an improvement of
      FA after both treatments. Laypeople rated FA higher compared to clinicians.

PMID- 23871271
TI  - Assessment of the safety of long-term bazedoxifene treatment on the reproductive
      tract in postmenopausal women with osteoporosis: results of a 7-year, randomized,
      placebo-controlled, phase 3 study.
AB  - OBJECTIVE: To evaluate the clinical safety of bazedoxifene (BZA) on the
      reproductive tract in postmenopausal women with osteoporosis over 7 years. STUDY
      DESIGN: This was a second, blinded, 2-year extension of a 3-year, randomized,
      double-blind, placebo (PBO)- and active-controlled phase 3 trial. In the core
      study, subjects were randomized to receive BZA 20 or 40mg, raloxifene 60mg, or
      PBO. During years 4-5, the raloxifene arm was discontinued and subjects receiving
      BZA 40mg were transitioned to BZA 20mg. Subjects continued to receive BZA 20mg or
      PBO during years 6-7. MAIN OUTCOME MEASURES: The primary endpoint was the
      incidence of new vertebral fractures at 7 years (reported separately).
      Reproductive tract safety findings at 7 years are reported here. Endometrial
      thickness was assessed by transvaginal ultrasonography for subjects in the
      endometrial safety substudy. Adverse events (AEs) were recorded throughout the
      study. RESULTS: At 7 years, the adjusted mean (+/-standard error) change in
      endometrial thickness was similar with BZA and PBO (-0.11 +/- 0.21 and 0.07 +/-
      0.32 mm, respectively). The incidence of endometrial hyperplasia was low (0.1%
      for both groups). BZA showed significantly lower rates than PBO of endometrial
      carcinoma (0.1% vs. 0.4%; P=0.020) and vaginitis (6.1% vs. 7.6%; P=0.035). There
      were more cases of ovarian carcinoma with BZA (n=4 [0.1%]) than PBO (n=0); the
      difference was not statistically significant. Rates of breast-related and other
      gynecologic AEs were similar among groups. CONCLUSIONS: BZA was associated with a
      favorable reproductive safety profile in postmenopausal women with osteoporosis
      over 7 years.

PMID- 23871273
TI  - [Bilateral ungual disorders with predominant radial involvement].

PMID- 23871272
TI  - Maternal periconceptional occupational exposure to pesticides and selected
      musculoskeletal birth defects.
AB  - This population-based U.S. study investigated the association between major
      musculoskeletal malformations and periconceptional maternal occupational
      pesticide exposure for a wide range of occupations. We conducted a multi-site
      case-control analysis using data from the National Birth Defects Prevention Study
      among employed women with due dates from October 1, 1997 through December 31,
      2002. Cases included 871 live-born, stillborn, or electively terminated fetuses
      with isolated craniosynostosis, gastroschisis, diaphragmatic hernia, or
      transverse limb deficiencies. Controls included 2857 live-born infants without
      major malformations. Using self-reported maternal occupational information, an
      industrial hygienist used a job-exposure matrix and expert opinion to evaluate
      the potential for exposure to insecticides, herbicides or fungicides for each job
      held during one month pre-conception through three months post-conception.
      Exposures analyzed included any exposure (yes/no) to pesticides, to insecticides
      only, to both insecticides and herbicides (I+H) and to insecticides, herbicides
      and fungicides (I+H+F). We used logistic regression to evaluate the association
      between exposures and defects, controlling for infant and maternal risk factors.
      Occupational exposure to I+H+F was associated with gastroschisis among infants of
      women aged 20 years or older (adjusted odds ratio [aOR]=1.88; 95% confidence
      interval [CI]: 1.16-3.05), but not for women under age 20 (aOR=0.48; 95% CI: 0.20
      1.16). We found no significant associations for the other defects. Additional
      research is needed to validate these findings in a separate population. 

PMID- 23871274
TI  - [Conceptual innovations and initiatives to improve palliative care in the xxi
      century].

PMID- 23871275
TI  - Clinical evaluation of SPECT/CT fusion imaging for the diagnosis and
      determination of localisation of cerebrospinal rhinorrhea.
AB  - OBJECTIVE: The objective was to evaluate the clinical value of the single photon
      emission computerized tomography/computed tomography (SPECT/CT) fusion imaging
      for the diagnosis and determination of localisation of cerebrospinal rhinorrhea.
      METHODS: A total of 33 patients with cerebrospinal rhinorrhea were preoperatively
      injected with (99m)Tc-diethylenetriamine pentaacetic acid (DTPA) through lumbar
      puncture and then subjected to planar imaging of the cistern 120 min and 180 min
      after operation. CT and ECT were then performed. Finally, the rhinorrhea ventage
      and leaking path were confirmed by fusion image analysis. RESULTS: Thirty-one
      patients who underwent fusion imaging and 30 patients who underwent planar
      imaging showed abnormal nuclide activity in the cavity between the basis cranii
      and the nose. After operation, 30 patients who underwent fusion imaging and 18
      patients who underwent planar imaging showed complete correction of the leakage.
      The diagnosis sensitivity and positional accuracy of fusion imaging were 93.9%
      (31/33) and 90.9% (30/33) at P>.05. The values of planar imaging were 93.5%
      (29/31) and 79.3% (23/29) at P<.05. CONCLUSION: (99m)Tc-DTPA SPECT/CT fusion
      imaging of the cistern is an efficient, simple, and accurate method that may be
      used for diagnosing and determining the localisation of cerebrospinal rhinorrhea
      ventage and leakage path.

PMID- 23871276
TI  - Diffusion-weighted MRI of the normal adult pancreas: the effect of age on
      apparent diffusion coefficient values.
AB  - AIM: To investigate and characterize the effect of age on apparent diffusion
      coefficient (ADC) values in the normal adult pancreas using diffusion-weighted
      magnetic resonance imaging (DWI). MATERIALS AND METHODS: Five hundred and fifty
      nine adult patients without pancreatic disease, ranging from 20-81 years of age
      (mean 50.9 years; 436 men, 123 women), were included in this study. Breath-hold
      single-shot echo-planar DWI (b-values = 0, 500 s/mm(2)) was employed to determine
      the ADCs across all patients. Dependency of ADCs on age was characterized using a
      Spearman rank-order correlation test. RESULTS: Across the age spectrum, there was
      no significant correlation between ADC and age (p = 0.409). CONCLUSION: The
      findings of the present study suggest that the effect of age on ADCs can be
      excluded from the diagnosis of pancreatic diseases and design of future studies
      using breath-hold single-shot DWI and ADCs (as calculated with b-values of 0 and
      500 s/mm(2)).

PMID- 23871277
TI  - Re: CO2 microbubble contrast enhancement in x-ray angiography. A reply.

PMID- 23871279
TI  - Anti-PGL1 salivary IgA/IgM, serum IgG/IgM, and nasal Mycobacterium leprae DNA in
      individuals with household contact with leprosy.
AB  - OBJECTIVES: Leprosy household contacts represent a group at high risk of
      developing the disease. The aim of this study was to detect Mycobacterium leprae
      subclinical infection in this group through serological and molecular parameters.
      METHODS: Serum anti-PGL1 IgG/IgM and salivary anti-PGL1 IgA/IgM was investigated
      using an ELISA, and nasal carriage of M. leprae DNA was detected by PCR, in
      leprosy household contacts of paucibacillary (PB) and multibacillary (MB)
      household leprosy patients (n=135), their index cases (n=30), and in persons
      living in a low endemic city (n=17). RESULTS: Salivary anti-PGL1 IgA and IgM and
      serum anti-PGL1 IgG showed good correlation comparing contacts and index cases
      (p<0.01, p<0.005, and p<0.0001, respectively). This was not observed for serum
      anti-PGL1 IgM (p>0.05). A high frequency of anti-PGL1 IgM positivity was found in
      IgG-negative samples (p<0.0001). For IgG-positive samples, IgM antibodies were
      also positive in most of the samples. None of the 17 volunteers living in a low
      endemic city presented seropositivity for IgG; however, two of them showed
      positivity for anti-PGL1 IgM. M. leprae DNA was found in the nasal swabs of nine
      out of the 85 MB household leprosy contacts (10.6%) and in three out of the 50 PB
      household leprosy contacts (6.0%). CONCLUSION: We strongly suggest that serum
      IgG/IgM and salivary anti-PGL1 IgA/IgM measurements are used to follow leprosy
      household contacts.

PMID- 23871278
TI  - CenteringPregnancy-Africa: a pilot of group antenatal care to address Millennium
      Development Goals.
AB  - BACKGROUND: severe health worker shortages and resource limitations negatively
      affect quality of antenatal care (ANC) throughout sub-Saharan Africa. Group ANC,
      specifically CenteringPregnancy (CP), may offer an innovative approach to enable
      midwives to offer higher quality ANC. OBJECTIVE: our overarching goal was to
      prepare to conduct a clinical trial of CenteringPregnancy-Africa (CP-Africa) in
      Malawi and Tanzania. In Phase 1, our goal was to determine the acceptability of
      CP as a model for ANC in both countries. In Phase 2, our objective was to develop
      CP-Africa session content consistent with the Essential Elements of CP model and
      with national standards in both Malawi and Tanzania. In Phase 3, our objective
      was to pilot CP-Africa in Malawi to determine whether sessions could be conducted
      with fidelity to the Centering process. SETTING: Phases 1 and 2 took place in
      Malawi and Tanzania. Phase 3, the piloting of two sessions of CP-Africa, occurred
      at two sites in Malawi: a district hospital and a small clinic. DESIGN: we used
      an Action Research approach to promote partnerships among university researchers,
      the Centering Healthcare Institute, health care administrators, health
      professionals and women attending ANC to develop CP-Africa session content and
      pilot this model of group ANC. PARTICIPANTS: for Phases 1 and 2, members of the
      Ministries of Health, health professionals and pregnant women in Malawi and
      Tanzania were introduced to and interviewed about CP. In Phase 2, we finalised CP
      Africa content and trained 13 health professionals in the Centering Healthcare
      model. In Phase 3, we conducted a small pilot with 24 pregnant women (12 at each
      site). MEASUREMENTS AND FINDINGS: participants enthusiastically embraced CP
      Africa as an acceptable model of ANC health care delivery. The CP-Africa content
      met both CP and national standards. The pilot established that the CP model could
      be implemented with process fidelity to the 13 Essential Elements. Several
      implementation challenges and strategies to address these challenges were
      identified. KEY CONCLUSIONS: preliminary data suggest that CP-Africa is feasible
      in resource-constrained, low-literacy, high-HIV settings in sub-Saharan Africa.
      By improving the quality of ANC delivery, midwives have an opportunity to make a
      contribution towards Millennium Development Goals (MDG) targeting improvements in
      child, maternal and HIV-related health outcomes (MDGs 4, 5 and 6). A clinical
      trial is needed to establish efficacy. IMPLICATIONS FOR PRACTICE: CP-Africa also
      has the potential to reduce job-related stress and enhance job satisfaction for
      midwives in low income countries. If CP can be transferred with fidelity to
      process in sub-Saharan Africa and retain similar results to those reported in
      clinical trials, it has the potential to benefit pregnant women and their infants
      and could make a positive contribution to MGDs 4, 5 and 6.

PMID- 23871280
TI  - Rickettsioses in the central hills of Sri Lanka: serological evidence of
      increasing burden of spotted fever group.
AB  - OBJECTIVES: To study the epidemiology, clinical features, and changing pattern of
      rickettsial infections on the western slopes of the hilly Central Province of Sri
      Lanka over 6 years. METHODS: All patients with rickettsial infections who
      presented to the Teaching Hospital, Peradeniya were studied prospectively from
      January 2002 to December 2007. An immunofluorescent antibody assay (IFA) was used
      to confirm the diagnosis. RESULTS: Of the 371 clinical cases of rickettsial
      infection, 122 underwent IFA to confirm the diagnosis. Species-specific IgG
      antibodies were positive in 105/122 (86.1%) cases: 43/105 (40.9%) to Rickettsia
      conorii and 6/105 (5.7%) to Orientia tsutsugamushi, with mixed antibody
      reactivity to more than one antigen in 56/105 (53.3%) cases, including Rickettsia
      typhi in 27/105 (25.7%). Among those with mixed IgG reactivity, IgM assays were
      used to detect pathogens responsible for acute infections. Finally, a total of 55
      spotted fever group (SFG) infections, seven scrub typhus infections, and one case
      of murine typhus were identified. Of the 105 positive cases, 53 (50.5%) were male
      and 52 (49.5%) were female, and the mean age was 40 years (range 11-83 years). In
      the SFG patients, 13/55 (24%) had severe vasculitis with fern leaf type skin
      necrosis and 17/55 (31%) had arthritis. Three patients (5%) had an altered level
      of consciousness. A patient with scrub typhus had transient deafness. None of the
      105 patients had an eschar. CONCLUSIONS: It appears that SFG rickettsioses are on
      the rise in the hilly Central Province of Sri Lanka, whilst murine typhus and
      scrub typhus are present at a lower rate.

PMID- 23871281
TI  - Current concepts in the diagnosis of blood stream infections. Are novel molecular
      methods useful in clinical practice?
AB  - The decision on the right empirical treatment in bacteremia places particular
      demands on the clinician. As long as no microbiological diagnosis can be
      immediately drawn, the clinical diagnosis together with knowledge of local
      antimicrobial resistance must determine the antimicrobial choice. The use of
      several amplification, hybridization, and mass spectrometry methods has been
      studied in patient cohorts in comparison with blood culture-based conventional
      techniques. However, no clinical outcome trials have been conducted in which the
      use of these novel methods would guide antimicrobial therapy. Local differences
      in bacterial antimicrobial resistance cause differences in the regional need for
      molecular methods for the early detection of resistance mechanisms. The
      implementation of novel methods in clinical use requires active discussion
      between laboratory experts and clinicians. Providing rapid susceptibility results
      using conventional methods can lead to timely changes to appropriate
      antimicrobial therapy and the costs are lower than with the molecular methods.
      Gram-stain information in combination with clinical data is an underestimated,
      underused, rapid, and economical means of assessing the etiology of blood stream
      infection. 

PMID- 23871282
TI  - Acceptance of cosmetic surgery, body appreciation, body ideal internalization,
      and fashion blog reading among late adolescents in Sweden.
AB  - This study examined adolescents' attitudes of cosmetic surgery, as well as the
      relationships between these attitudes, body appreciation, body ideal
      internalization, and fashion blog reading. The sample comprised 110 (60 boys, 50
      girls) late adolescents (mean age 16.9 years) from a Swedish high school. The
      results indicated that younger adolescents seem somewhat more accepting of
      cosmetic surgery. This was especially the case for boys' acceptance of social
      motives for obtaining cosmetic surgery (boys' M=2.3+/-1.55 vs. girls' M=1.7+/
      0.89). Girls', and to a limited extent boys', internalization of the thin ideal
      was related to more favorable cosmetic surgery attitudes. Athletic ideal
      internalization and body appreciation were unrelated to these attitudes. Finally,
      girls who frequently read fashion blogs reported higher thin ideal
      internalization, and also demonstrated a slight tendency of more cosmetic surgery
      consideration. 

PMID- 23871283
TI  - A semi-automatic microextraction in packed sorbent, using a digitally controlled
      syringe, combined with ultra-high pressure liquid chromatography as a new and
      ultra-fast approach for the determination of prenylflavonoids in beers.
AB  - In this work a highly selective and sensitive analytical procedure based on semi
      automatic microextraction by packed sorbents (MEPS) technique, using a new
      digitally controlled syringe (eVol((r))) combined with ultra-high pressure liquid
      chromatography (UHPLC), is proposed to determine the prenylated chalcone derived
      from the hop (Humulus lupulus L.), xanthohumol (XN), and its isomeric flavonone
      isoxanthohumol (IXN) in beers. Extraction and UHPLC parameters were accurately
      optimized to achieve the highest recoveries and to enhance the analytical
      characteristics of the method. Important parameters affecting MEPS performance,
      namely the type of sorbent material (C2, C8, C18, SIL, and M1), elution solvent
      system, number of extraction cycles (extract-discard), sample volume, elution
      volume, and sample pH, were evaluated. The optimal experimental conditions
      involves the loading of 500MUL of sample through a C18 sorbent in a MEPS syringe
      placed in the semi-automatic eVol((r)) syringe followed by elution using 250MUL
      of acetonitrile (ACN) in a 10 extractions cycle (about 5min for the entire sample
      preparation step). The obtained extract is directly analyzed in the UHPLC system
      using a binary mobile phase composed of aqueous 0.1% formic acid (eluent A) and
      ACN (eluent B) in the gradient elution mode (10min total analysis). Under
      optimized conditions good results were obtained in terms of linearity within the
      established concentration range with correlation coefficients (R) values higher
      than 0.986, with a residual deviation for each calibration point below 12%. The
      limit of detection (LOD) and limit of quantification (LOQ) obtained were 0.4ngmL(
      1) and 1.0ngmL(-1) for IXN, and 0.9ngmL(-1) and 3.0ngmL(-1) for XN, respectively.
      Precision was lower than 4.6% for IXN and 8.4% for XN. Typical recoveries ranged
      between 67.1% and 99.3% for IXN and between 74.2% and 99.9% for XN, with relative
      standard deviations %RSD no larger than 8%. The applicability of the proposed
      analytical procedure in commercial beers, revealed the presence of both target
      prenylchalcones in all samples being IXN the most abundant with concentration of
      between 0.126 and 0.200MUgmL(-1). 

PMID- 23871284
TI  - Study on steric transition in asymmetrical flow field-flow fractionation and
      application to characterization of high-energy material.
AB  - In field-flow fractionation (FFF), there is the 'steric transition' phenomenon
      where the sample elution mode changes from the normal to steric/hyperlayer mode.
      Accurate analysis by FFF requires understanding of the steric transition
      phenomenon, particularly when the sample has a broad size distribution, for which
      the effect by combination of different modes may become complicated to interpret.
      In this study, the steric transition phenomenon in asymmetrical flow FFF (AF4)
      was studied using polystyrene (PS) latex beads. The retention ratio (R) gradually
      decreases as the particle size increases (normal mode) and reaches a minimum (Ri)
      at diameter around 0.5MUm, after which R increases with increasing diameter
      (steric/hyperlayer mode). It was found that the size-based selectivity (Sd) tends
      to increase as the channel thickness (w) increases. The retention behavior of
      cyclo-1,3,5-trimethylene-2,4,6-trinitramine (commonly called 'research department
      explosive' (RDX)) particles in AF4 was investigated by varying experimental
      parameters including w and flow rates. AF4 showed a good reproducibility in size
      determination of RDX particles with the relative standard deviation of 4.1%. The
      reliability of separation obtained by AF4 was evaluated by transmission electron
      microscopy (TEM). 

PMID- 23871285
TI  - Speciation analysis of arsenic compounds by capillary electrophoresis on-line
      coupled with inductively coupled plasma mass spectrometry using a novel
      interface.
AB  - In this work, a capillary electrophoresis (CE) coupled with inductively coupled
      plasma mass spectrometer (ICP-MS) system was developed for the simultaneous
      determination of ten arsenic compounds including arsenite, arsenate,
      monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, arsenocholine, 3
      nitro-4-hydroxyphenylarsonic acid, o-Arsanilic acid, p-ureidophenylarsonic acid,
      and 4-nitrophenylarsonic acid. The CE-ICP-MS system was hyphenated by a novel and
      high efficient interface which was directly used as the nebulizer. The separation
      was achieved on a 100cm length*50MUm ID fused-silica capillary. Analytical
      conditions such as electrophoretic buffer composition, concentration and pH
      value, separation voltage, methanol concentration in the sheath flow liquid and
      sample injection time were optimized. Baseline separation of the ten arsenic
      species was achieved using an electrophoretic buffer consisting of 12mM NaH2PO4
      and 8mM HBO3 at pH 9.20 with an applied voltage of +30kV. The detection limits of
      the ten arsenic compounds ranged from 0.9 to 3.0ngAsg(-1), corresponding to
      absolute detection limits in the range of 19-65fg As and the relative standard
      deviations (RSD, n=5) were below 1.5%, 5.7% and 4.8% for migration time, peak
      height and peak area, respectively. This method was successfully applied to
      determine various arsenicals in two certified reference materials (TORT-2 and
      DORM-3) and environmental samples such as ground water samples, herbal plants and
      chicken meat. 

PMID- 23871286
TI  - Evaluation and characterization of axial distribution in expanded bed. I. Bead
      size, bead density and local bed voidage.
AB  - Expanded bed adsorption (EBA) is an innovative chromatography technology that
      allows the adsorption of target proteins directly from unclarified feedstock, and
      the most important property of an expanded bed is the perfectly classified
      fluidization of resin beads in the column. Due to the variation of both size and
      density of bulk resin beads, the axial distributions of bead size, bead density
      and bed voidage are the inherent characteristics of an expanded bed. However, the
      understanding on these properties is quite limited. In this study, raw beads (3%
      crosslinked agarose containing tungsten carbide) and 2cm-diameter nozzle column
      were used as the model system and mean bead size, bead density and local bed
      voidage along the bed height were measured systematically with the in-bed
      sampling method for two settled bed heights (11.5 and 23.1cm) and different
      expansion factors (1.4-2.6). With the increase of bed height, mean bead size and
      wet density of the beads decreased from 140 to 90MUm and from 4 to 2g/ml,
      respectively. The local bed voidage increased from 0.6 to 0.9 with the increasing
      bed height. The relative bed height and relative bed voidage were introduced to
      describe the general rule of axial distribution. Some empirical equations were
      used to correlate the mean bead size, bead density and local bed voidage along
      the bed height with the standard deviations of 10.6%, 6.1% and 5.5, respectively.
      In addition, a general equation was proposed to predict the axial distributions
      of bead size, bead density and local bed voidage in the column with standard
      deviations less than 10% for most of the experimental data, which would be useful
      for the characterization of resin beads distribution in an expanded bed under
      varying operation conditions. 

PMID- 23871287
TI  - Autoprotease N(pro): analysis of self-cleaving fusion protein.
AB  - A reversed phase high pressure liquid chromatography method was developed for
      determination of in vitro refolding and cleavage kinetics for the N(pro)
      autoprotease fusion peptide EDDIE-pep6His using a TSK Super-Octyl column with a
      segmented acetonitrile gradient. Self-cleaving fusion proteins such as N(pro)
      autoprotease fusion proteins consist of the single autoprotease N(pro) and a
      target peptide or a target protein as fusion partner. Hence, three protein
      species are present after self-cleavage: the target peptide or protein, the
      single N(pro) autoprotease and, in case of incomplete cleavage, residual N(pro)
      fusion protein. Thus, for an accurate analysis the method must be standardized
      for three components in the presence of host cell impurities. For method
      validation, protein standards of EDDIE-pep6His and the single N(pro) autoprotease
      EDDIE were prepared from inclusion bodies (IBs) by ion exchange, immobilized
      metal ion affinity, size exclusion, and reversed phase chromatography. A linear
      correlation was obtained for EDDIE-pep6His and EDDIE in the range from 95 to
      730MUg/ml with a lower limit of quantification (LLOQ) and a lower limit of
      detection (LLOD) of 34.5 and 11.4MUg/ml, respectively, for EDDIE-pep6His and 39.6
      and 13.1MUg/ml, respectively, for EDDIE. Finally, a fully automated batch
      refolding of EDDIE-pep6His from IBs was performed to demonstrate the
      applicability of this method. It was shown that the initial EDDIE-pep6His
      concentration in the refolding solution decreased from 194.3 to 83.8MUg/ml over a
      refolding time of 385min resulting in a final refolding and cleavage yield of
      50%. 

PMID- 23871288
TI  - An interactive study of influential parameters for shikimic acid production using
      statistical approach, scale up and its inhibitory action on different lipases.
AB  - Shikimic acid is the promising candidate as a building block for the industrial
      synthesis of drug Tamiflu used for the treatment of Swine flu. The fermentative
      production process using microbes present an excellent and even more sustainable
      alternative to the traditional plants based extraction methods. In the present
      study, the fermentative production of shikimic acid by Citrobacter freundii GR-21
      (KC466031) was optimized by process engineering using a statistical modeling
      approach and a maximum amount of 16.78 g L(-1) was achieved. The process was also
      scaled up to 14L bioreactor to validate the production of shikimic acid. Further,
      the potential of anti-enzymatic nature of purified shikimic acid was evaluated
      for different lipases wherein, shikimic acid inhibited the hydrolysis of
      triglycerides by 55-60%. Shikimic acid also profoundly inhibited pancreatic
      lipase activity by 66%, thus providing another valuable therapeutic aspect for
      treating diet induced obesity in humans.

PMID- 23871289
TI  - Mammalian target of rapamycin pathway activity in alveolar soft part sarcoma.
AB  - Alveolar soft part sarcoma (ASPS) is a distinct type of soft tissue sarcoma
      holding a specific ASPL-TFE3 fusion transcript. Curative therapy is based on
      surgical removal, whereas lately, antiangiogenic targeted therapy regimens have
      proven effective. In ASPS, analysis of small series additionally display mTOR
      (mammalian target of rapamycin) pathway activity, thus making mTOR a possible
      additive target in ASPS, because it is in other tumor entities. Therefore, we
      systematically evaluated mTOR pathway activity in a large series of ASPS in
      comparison with soft tissue sarcomas of other differentiation (non-ASPS).
      Upstream and downstream factors of mTOR signaling and ancillary targets were
      analyzed in 103 cases (22 ASPS, 81 non-ASPS) by immunohistochemistry mostly using
      phospho-specific antibodies. TFE3 (transcription factor for immunoglobulin heavy
      chain enhancer 3) translocation status was determined by FISH and RT-PCR. All
      ASPS were positive in TFE3 break-apart FISH and exhibited specific fusion
      products when RNA was available (type 1: 9x, type 2: 11x), whereas TFE3
      immunoreactive non-ASPS did not. In ASPS, TFE3-, cMET-, pAKT T308- (all P <
      .0001), pp70S6K- (P = .002), and p4EBP1 (P = .087) expression levels were
      elevated, whereas pAKT S473 was decreased (P < .0001). In addition, ASPS
      exhibited higher TFE3-, cMET-, pAKT T308-, and pp70S6K- expression levels
      compared with TFE3-immunopositive non-ASPS sarcomas (all P < .001). We
      demonstrate elevated mTOR complex 1 (mTORC1) activity in ASPS independent of mTOR
      complex 2 (mTORC2) activation. mTORC1 activity seems to be related to the
      existence of ASPL-TFE3 fusion transcripts because TFE3-immunoreactive non-ASPS
      without ASPL-TFE3 fusion transcripts exhibit significantly lower mTORC1
      activation status. Small molecule-based targeting of mTOR might therefore
      represent a potential mechanism in ASPS alone or in combination with contemporary
      upstream approaches. 

PMID- 23871290
TI  - Enhancing the informed consent process for critical care research: strategies
      from a thromboprophylaxis trial.
AB  - BACKGROUND: Critically ill patients lack capacity for decisions about research
      participation. Consent to enrol these patients in studies is typically obtained
      from substitute decision-makers. OBJECTIVE: To present strategies that may
      optimise the process of obtaining informed consent from substitute decision
      makers for participation of critically ill patients in trials. We use examples
      from a randomised trial of heparin thromboprophylaxis in the intensive care unit
      (PROTECT, clinicaltrials.gov NCT00182143). METHODS: 3764 patients were
      randomised, with an informed consent rate of 82%; 90% of consents were obtained
      from substitute decision-makers. North American PROTECT research coordinators
      attended three meetings to discuss enrolment: (1) Trial start-up (January 2006);
      (2) Near trial closure (January 2010); and (3) Post-publication (April 2011).
      Data were derived from slide presentations, field notes from break-out groups and
      plenary discussions, then analysed inductively. RESULTS: We derived three phases
      for the informed consent process: (1) Preparation for the Consent Encounter; (2)
      The Consent Encounter; and (3) Follow-up to the Consent Encounter. Specific
      strategies emerged for each phase: Phase 1 (four strategies); Phase 2 (six
      strategies); and Phase 3 (three strategies). CONCLUSION: We identified 13
      strategies that may improve the process of obtaining informed consent from
      substitute decision-makers and be generalisable to other settings and studies.

PMID- 23871291
TI  - Do families after early postnatal discharge need new ways to communicate with the
      hospital? A feasibilility study.
AB  - OBJECTIVE: the length of the postnatal hospital stay in Denmark as well as
      globally has been radically reduced over the past 10-20 years and this raises the
      challenge of finding new ways of providing observation and support to families
      discharged early, that they otherwise would be provided as inpatients. AIM: this
      study is to identify the nursing support needs of new parents and their infants
      during the first seven days post partum, by drawing on the experiences of all
      stakeholders' in early postnatal discharge from hospital, and thereby gaining new
      knowledge to investigate further whether telemedicine is a viable option in
      providing the required support. DESIGN: this article describes the first phase of
      a participatory design process. A qualitative approach guided the research
      process and the data analysis. Data were collected from participant observation,
      qualitative interviews with the new parents, focus groups interviews and a
      workshop attended by the new parents and health-care professionals. PARTICIPANTS
      AND SETTING: the total number of participants in this study was 37; nineteen
      parents and 18 health-care professionals from one hospital and three
      municipalities in Denmark. FINDINGS: the investigation findings highlighted,
      amongst other aspects, the importance of individualised postnatal follow-up in
      which families have increased access to the health-care professionals and are
      provided with timely information tailored to their specific needs. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the present study underscored that the
      families experiencing early discharge were not provided with seamless
      individualised follow-up support. They requested more availability from the
      health-care system to respond to their concerns and questions during the
      postnatal period. They experienced a barrier in attempting to contact health-care
      professionals following hospital discharge and they asked for new ways to
      communicate that would eliminate that barrier and meet their needs for more
      individualised and timely information and guidance.

PMID- 23871292
TI  - Antibiotic resistance.

PMID- 23871293
TI  - The impact of frozen section analysis during partial nephrectomy on surgical
      margin status and tumor recurrence: a clinicopathologic study of 433 cases.
AB  - BACKGROUND: Frozen section analysis (FSA) is frequently performed during partial
      nephrectomy (PN) to ensure complete tumor resection. We investigate the utility
      of intraoperative FSA by evaluating its impact on final surgical margin (SM)
      status and on patient outcomes. PATIENTS AND METHODS: We retrospectively analyzed
      a consecutive series of patients (n = 433, including 326 with renal cell
      carcinomas [RCCs]) undergoing PN (n = 447; 136 open/311 laparoscopic) for a
      suspected renal tumor at the University of Rochester Medical Center from 2004 to
      2012. RESULTS: FSA was performed in 293 patients (67.7%) undergoing 300 PNs
      (67.1%). Overall, positive SMs were found significantly more often (P < .001) in
      the no FSA group (17.7%) than in the FSA group (4.3%). Performing FSA also
      resulted in significant decreases in the rate of positive SM in the following
      subgroups of patients with RCC undergoing PN laparoscopically: clear-cell (P =
      .002)/papillary (P = .041) subtypes, upper (P = .004)/mid (P = .022) pole tumors,
      exophytic (P = .029)/endophytic (P = .014) tumors, pT1a (P < .001)/pT1 (P < .001)
      tumors, and Fuhrman grades 1 to 2 (P = .004)/2 (P = .007) tumors. Kaplan-Meier
      analysis in RCC cases revealed that FSA did not considerably contribute to
      preventing recurrence (P = .114). However, performing FSA during laparoscopic PN
      strongly correlated with improved recurrence-free survival in patients with pT1
      (P = .004) or exophytic (P = .011) RCC. No impact of FSA on recurrence was seen
      in any subgroup of patients undergoing open surgery. CONCLUSIONS: Although FSA
      reduces the risk of positive SMs, our data may argue against routine FSA during
      PN that does not affect patient outcomes overall. However, FSA may be useful in
      select patients who have pT1 or exophytic tumor and undergo laparoscopic PN.

PMID- 23871294
TI  - Infectious Pseudomonas scleritis after strabismus surgery.
AB  - Scleral inflammation and necrosis are rare but serious complications of ocular
      surgery. We present a case of Pseudomonas infectious scleritis following
      strabismus surgery with an exuberant, presumably sterile endophthalmitis in an
      immunocompromised 62-year-old man that was responsive to topical and oral
      antibiotics. 

PMID- 23871295
TI  - Electroretinography combined with spectral domain optical coherence tomography to
      detect retinal damage in shaken baby syndrome.
AB  - In order to correlate anatomical changes with visual function in shaken baby
      syndrome, we performed electroretinography and spectral domain optical coherence
      tomography on a 2-month-old girl and a 9-month-old girl after the retinal
      hemorrhages absorbed. Both patients had significant abnormalities in spectral
      domain optical coherence tomography images of the macular area. The amplitudes of
      the focal macular electroretinograms were more severely decreased than those of
      the full-field electroretinograms. Combining spectral domain coherence tomography
      with focal macular electroretinograms might better estimate the functional damage
      to the macula in patients with shaken baby syndrome. 

PMID- 23871296
TI  - Solitary mastocytoma of the eyelid.
AB  - Mastocytosis is a heterogeneous group of diseases characterized by the
      proliferation and abnormal infiltration of mast cells in tissue. These
      collections of mast cells are called mastocytomas. Solitary mastocytomas are
      cutaneous lesions, most commonly involving the extremities and trunk. Rubbing a
      cutaneous mastocytoma lesion leads to the release of histamine and other chemical
      mediators causing the lesion to become elevated and urticarial, similar to an
      allergic reaction. We describe a rare location of a presumed solitary mastocytoma
      of the lower eyelid in a young otherwise healthy child. 

PMID- 23871297
TI  - Definition and evolution of a new symbiovar, sv. rigiduloides, among Ensifer
      meliloti efficiently nodulating Medicago species.
AB  - Understanding functional diversity is one of the main goals of microbial ecology,
      and definition of new bacterial ecotypes contributes significantly to this
      objective. Nitrogen-fixing bacteria provide a good system for investigation of
      ecotypes/biovars/symbiovars, as they present different specific associations with
      several host plants. This specific symbiosis is reflected both in the nodulation
      and fixation efficiency and in genetic characters of the bacteria, and several
      biovars have already been described in the bacterial species Ensifer meliloti. In
      the present study, the species affiliation of E. meliloti strains trapped from
      nodules sampled from Medicago rigiduloides roots was analyzed using housekeeping
      recA genes and DNA-DNA hybridization. The genetic diversity of these isolates was
      also investigated using several symbiotic markers: nodulation (nodA, nodB, nodC)
      and nitrogen fixation (nifH) genes, as well as the performance of phenotypic
      tests of nodulation capacity and nitrogen fixation efficiency. These analyses led
      to the proposal of a new bacterial symbiovar, E. meliloti sv. rigiduloides, that
      fixed nitrogen efficiently on M. rigiduloides, but not on Medicago truncatula.
      Using phylogenetic reconstructions, including the different described symbiovars,
      several hypotheses of lateral gene transfer and gene loss are proposed to explain
      the emergence of symbiovars within this species. The widespread geographical
      distribution of this symbiovar around the Mediterranean Basin, in contrast to
      restriction of M. rigiduloides to Eastern European countries, suggests that these
      isolates might also be associated with other plant species. The description of a
      new symbiovar within E. meliloti confirms the need for accurate bacterial
      ecological classification, especially for analysis of bacterial populations. 

PMID- 23871298
TI  - Effect of long-term salinity on cellular antioxidants, compatible solute and
      fatty acid profile of Sweet Annie (Artemisia annua L.).
AB  - Impact of long-term salinity and subsequent oxidative stress was studied on
      cellular antioxidants, proline accumulation and lipid profile of Artemisia annua
      L. (Sweet Annie or Qinghao) which yields artemisinin (Qinghaosu), effective
      against cerebral malaria-causing strains of Plasmodium falciparum. Under salinity
      (0.0-160 mM NaCl), in A. annua, proline accumulation, contents of ascorbate and
      glutathione and activities of superoxide dismutase (SOD), ascorbate peroxidase
      (APX), glutathione reductase (GR) and catalase (CAT) increased, but the contents
      of reduced forms of glutathione (GSH) and ascorbate declined. The fatty-acid
      profiling revealed a major salinity-induced shift towards long-chain and mono
      saturated fatty acids. Myristic acid (14:0), palmitoleic acid (16:1), linoleic
      acid (18:2) and erucic acid (22:1) increased by 141%, 186%, 34% and 908%,
      respectively, in comparison with the control. Contents of oleic acid (18:1),
      linolenic acid (18:3), arachidonic acid (22:0) and lignoceric acid (24:0)
      decreased by 50%, 17%, 44% and 78%, respectively. Thus, in A. annua, salinity
      declines ascorbate and GSH contents. However, increased levels of proline and
      total glutathione (GSH+GSSG), and activities of antioxidant enzymes might provide
      a certain level of tolerance. Modification in fatty-acid composition might be a
      membrane adaptation to long-term salinity and oxidative stress.

PMID- 23871299
TI  - Supporting student nurses in practice with additional online communication tools.
AB  - Student nurses' potential isolation and difficulties of learning on placement
      have been well documented and, despite attempts to make placement learning more
      effective, evidence indicates the continuing schism between formal learning at
      university and situated learning on placement. First year student nurses,
      entering placement for the first time, are particularly vulnerable to the
      vagaries of practice. During 2012 two first year student nurse seminar groups (52
      students) were voluntarily recruited for a mixed method study to determine the
      usage of additional online communication support mechanisms (Facebook, wiki, an
      email group and traditional methods of support using individual email or phone)
      while undertaking their first five week clinical placement. The study explores
      the possibility of strengthening clinical learning and support by promoting the
      use of Web 2.0 support groups for student nurses. Results indicate a high level
      of interactivity in both peer and academic support in the use of Facebook and a
      high level of interactivity in one wiki group. Students' qualitative comments
      voice an appreciation of being able to access university and peer support whilst
      working individually on placement. Recommendations from the study challenge
      universities to use online communication tools already familiar to students to
      complement the support mechanisms that exist for practice learning. This is
      tempered by recognition of the responsibility of academics to ensure their
      students are aware of safe and effective online communication. 

PMID- 23871300
TI  - Nursing students evaluation of problem based learning and the impact of culture
      on the learning process and outcomes: a pilot project.
AB  - PURPOSES: This study evaluates students' learning experiences in a clinical
      pediatric nursing course adopting Problem Based Learning (PBL) and investigates
      how students' cultural background impacts on self directed learning. METHODS: A
      mixed-methods approach combining quantitative and qualitative methods was
      utilized to answer the research objectives. An observational technique for the
      PBL teaching sessions was employed; and 226 third-year students were asked to
      complete PBL evaluation questionnaire. RESULTS: Fifty seven percent (n = 130)
      responses to the questionnaire were analyzed. Overall, students considered PBL to
      be moderately effective in their learning experience, with a mean of 3.64 (S.D =
      1.18). Students qualitative responses fell within four thematic categories
      including: developing cognitive abilities, independent learning, motivation to
      learn, and group learning. Difficulties encountered by students were: it is time
      consuming, it has unclear objectives, it is a stressful process, and it results
      in an increased workload. A small number of students indicated that PBL tutorials
      were boring and complained about lack of contribution from instructors and
      limited recourses. Learning is intertwined with culture; students' previous
      educational experiences, uncertainty, English language proficiency, computer
      resources, gender, and achievement were identified as the most important cultural
      issues that impact the learning process and outcomes. CONCLUSION: Successful
      implementation of PBL does not come easily; teachers should be alert to the
      issues of culture in designing curriculum.

PMID- 23871301
TI  - Polymethylmethacrylate dermal fillers: evaluation of the systemic toxicity in
      rats.
AB  - This study evaluated local and systemic reactions after an intravascular
      injection of polymethylmethacrylate (PMMA) at two concentrations in a murine
      model. Thirty rats were divided equally into three groups: 2% PMMA, 30% PMMA, and
      a control group (normal saline only injection). The filler was injected into the
      ranine vein. The rats were sedated at 7 and 90 days and a clinical evaluation
      performed. After euthanasia, the right lung, liver, and right kidney were
      removed, weighed, and microscopically analyzed. The submandibular lymph nodes and
      tongue were removed and examined microscopically. Serum was subjected to liver
      and kidney function tests. No groups showed clinical alterations. Microspheres
      were not observed at any distant organ. Two samples from the 2% PMMA group showed
      a local inflammatory response at day 7 and another two samples from the 30% PMMA
      group at day 90. The group injected with 30% PMMA presented higher levels of
      alanine aminotransferase (P = 0.047) after 90 days when compared with the other
      groups. The data obtained in this study demonstrate that intravascular injections
      of PMMA fillers show potential health risks such as chronic inflammation at the
      implantation site.

PMID- 23871302
TI  - Defining the role of catheter ablation for atrial fibrillation in Australia.

PMID- 23871303
TI  - Occupational radiation exposure during endovascular aortic procedures.
AB  - OBJECTIVES: To measure the radiation exposure of the operating team during
      endovascular aortic procedures, and to determine factors that predict high
      exposures. MATERIALS AND METHODS: Electronic dosimeters placed over and under
      protective lead garments, were used to prospectively record radiation exposure
      during endovascular aortic repairs performed in a designated interventional
      radiology suite. Univariate and multivariate linear regression analyses of
      predictors of radiation exposure were performed. RESULTS: A total of 26 infra
      renal and 10 thoracic endovascular cases were studied. Median (IQR) patient age
      and body mass index were 76.0 (70.0-81.8) years and 26.2 (23.9-28.9) kg/m(2)
      respectively. Over-lead exposure to the operator was higher for thoracic than for
      infra-renal procedures (421.0 [233.8-597.8] MUSv vs. 52.5 [27.8-179.8] MUSv, p =
      .0003), reflecting a significant exposure to unprotected parts of the body. Under
      lead exposures for operator and assistant were 5.5 (2.0-14.2) MUSv and 1.0 (0.0
      2.3) MUSv respectively, which for an average caseload would comply with total
      body effective dose limits. Type of case and percentage of digital subtraction
      angiography (DSA) time in left anterior oblique angulations predicted dose to the
      operator (p < .0001). CONCLUSIONS: Thoracic procedures, DSA runs and obliquity of
      the C-arm are strong predictors of radiation exposure during endovascular aortic
      repairs. Understanding scatter radiation dynamics and instigating measures to
      minimise radiation exposure should be mandatory.

PMID- 23871304
TI  - Effects of foot orthoses on the temporal pattern of muscular activity during
      walking.
AB  - BACKGROUND: Several studies have described the biomechanical effects of foot
      orthotics, as well as their effects at the level of muscular recruitment.
      Although the latter effect is unlikely to be limited to muscular intensity, the
      temporal pattern of activity of the muscles involved in walking with orthoses is
      still unclear. METHODS: Twelve adults with everted static rearfoot posture higher
      than 5 degrees  of valgus participated in the study. For all participants, the
      kinematic data and the muscular temporal activity of the tibialis anterior, the
      soleus, the gastrocnemius medialis, the gastrocnemius lateralis and the peroneus
      longus were measured under two experimental conditions, walking with and without
      custom-made orthoses. Data were recorded and analyzed using a motion analysis and
      a surface EMG system. FINDINGS: The results showed that, when walking with
      insoles, the activity of the tibialis anterior, the soleus, the gastrocnemius
      medialis, the gastrocnemius lateralis and the peroneus longus is shorter than
      walking without orthoses. Furthermore, when walking with orthoses, the activity
      of the soleus and the gastrocnemius medialis is delayed. INTERPRETATION: Our
      study corroborates that the realignment of the calcaneus with the talus decreases
      the range of eversion and inversion of midfoot. Moreover, it reports noticeable
      modifications on the start time and the duration of the muscular activity of the
      tibialis anterior, soleus, gastrocnemii and peroneus longus while using foot
      orthoses.

PMID- 23871305
TI  - Height restoration and maintenance after treating unstable osteoporotic vertebral
      compression fractures by cement augmentation is dependent on the cement volume
      used.
AB  - BACKGROUND: Two different procedures, used for percutaneous augmentation of
      vertebral compression fractures were compared, with respect to height restoration
      and maintenance after cyclic loading. Additionally the impact of the cement
      volume used was investigated. METHODS: Wedge compression fractures were created
      in 36 human cadavaric vertebrae (T10-L3). Twenty-seven vertebrae were treated
      with the SpineJack(r) with different cement volumes (maximum, intermediate, and
      no cement), and 9 vertebrae were treated with Balloon Kyphoplasty. Vertebral
      heights were measured pre- and postfracture as well as after treatment and
      loading. Cyclic loading was performed with 10,000cycles (1Hz, 100-600N).
      FINDINGS: The average anterior height after restoration was 85.56% for
      Kyphoplasty; 96.20% for SpineJack(r) no cement; 93.44% for SpineJack(r) maximum
      and 96% for the SpineJack(r) intermediate group. The average central height after
      restoration was 93.89% for Kyphoplasty; 100.20% for SpineJack(r) no cement;
      99.56% for SpineJack(r) maximum and 101.13% for the SpineJack(r) intermediate
      group. The average anterior height after cyclic loading was 85.33 % for
      Kyphoplasty; 87.30% in the SpineJack(r) no cement, 92% in the SpineJack(r)
      maximum and 87% in the SpineJack(r) intermediate group. The average central
      height after cyclic loading was 92% for Kyphoplasty; 93.80% in the SpineJack(r)
      no cement; 98.56% in the SpineJack(r) maximum and 94.25% in the SpineJack(r)
      intermediate group. INTERPRETATION: Height restoration was significantly better
      for the SpineJack(r) group compared to Kyphoplasty. Height maintenance was
      dependent on the cement volume used. The group with the SpineJack(r) without
      cement nevertheless showed better results in height maintenance, yet the
      statistical significance could not be demonstrated.

PMID- 23871306
TI  - Solomon V. Shereshevsky: the great Russian mnemonist.
AB  - A biographical sketch is given of Solomon V. Shereshevsky, a man gifted with
      exceptional memory skills who became famous after the publication of Aleksandr R.
      Luria's book The Mind of a Mnemonist, in 1968. 

PMID- 23871307
TI  - Explaining altered cerebral functioning following cerebral damage.

PMID- 23871308
TI  - The role and management of sympathetic overactivity in cardiovascular and renal
      complications of diabetes.
AB  - Feedback activation of neurohormonal pathways in the setting of kidney or heart
      failure contributes to the development and progression of dysfunction in the
      other. Diabetes and its management independently activate these same pathogenic
      pathways, feeding into this vicious cycle and contributing to a poor prognosis.
      One of the most important of these neurohormonal pathways is the sympathetic
      nervous system (SNS). The activity of the SNS in increased in patients with
      chronic kidney disease, even in the absence of renal impairment or heart failure.
      There is a strong relationship between SNS overactivity and prognosis, and
      evidence that blockade of SNS reduces morbidity and mortality in patients with
      diabetes. However, modulation of SNS is underutilised as a strategy to protect
      both the diabetic kidney and the heart. This is partly because of the
      historically poor tolerability, adverse haemodynamic and metabolic effects, lack
      of selectivity of beta-blockers and the lack of specificity of other
      interventions that might modify SNS activation. The advent of "vasodilating beta
      blockers" with better tolerability as well as more favourable effects on renal
      function and metabolic profiles opens the door for their more widespread utility
      in patients with diabetes. Radiofrequency renal sympathectomy and baroreflex
      activation technologies also offer exciting new ways to tackle the challenge of
      sympathetic overactivity. 

PMID- 23871309
TI  - Small angle X-ray scattering study of carbon nanotube forests densified into long
      range patterns by controlled solvent evaporation.
AB  - Although emergent properties from self-assembly of carbon nanotubes have been
      described in various forms there is so far no systematic process for the
      preparation of dense arrays of aligned nanotubes. Here we present a systematic
      study on the analysis of the alignment of carbon nanotubes within solvent
      densified carbon nanotube forests. Highly periodic patterns with length scales of
      the order of the millimetres were generated and characterized by electron and
      optical micrographs and compared to results from small angle X-ray scattering
      performed at various incident beam angles. The impact of the different solvents
      was also discussed in light of the densification process and in relation to
      solvent properties. 

PMID- 23871310
TI  - Adsorption of sodium hexanoate on alpha-alumina.
AB  - Neutron reflection and adsorption isotherm measurements have been used to study
      the adsorption behaviour of hexanoic acid onto alpha-alumina surfaces.
      Importantly, the pH dependence of the behaviour has been characterised with a
      pronounced maximum in adsorption identified at a pH of approximately 5, close to
      the pKa of the acid. The adsorbed layer is identified as a bilayer, which is
      reasonable given the hydrophilic nature of both side of the layer, and has a
      thickness of 13 A, suggesting significant extent of interdigitation. At pH 5, the
      layer has much lower extent of hydration relative to the higher pH of 7,
      consistent with the increased total adsorption at pH 5. A number of different
      mechanisms for the binding of the hexanoic acid to the surface are considered.
      The experimental data, combined with calculations using equilibrium/binding
      constants of the surface and ligands, indicates that a ligand exchange reaction
      may be the most significant mechanism.

PMID- 23871311
TI  - Effect of molecular structure and packing density of an azo self-assembled
      monolayer on liquid crystal alignment.
AB  - We studied the alignment of liquid crystals (LCs) on a photo-switchable azo
      containing self-assembled monolayer (azo-SAM) with different packing densities
      and molecular structures. The packing density of the azo-SAM substrates was
      varied by changing the dipping time of the substrate in azosilane monomers
      solution (2mM in toluene). The thickness of the monolayer on the silicon
      substrate increased as the dipping time was increased. The relative surface
      packing density on the glass substrates was estimated from the surface energies
      of the azo-SAM. The photo-induced dynamics of liquid crystal alignment on the azo
      SAM significantly varied according to the packing density of the azo-SAM and the
      structure of the azo-SAM molecules. The azo-SAM from long octyloxy chain
      terminated azosilane (azo-S1) possessed stable homeotropic alignment even after
      photobuffing, while the azo-SAM from short methyl group-terminated azosilane
      monomer (azo-S2) showed photo-switchable homeotropic and planar alignments.
      However, when the packing density was increased to an excessive degree, even the
      azo-SAM from azo-S2 exhibited stable homeotropic alignment regardless of
      photobuffing. 

PMID- 23871312
TI  - Functionalized Au/Ag nanocages as a novel fluorescence and SERS dual probe for
      sensing.
AB  - We obtained chitosan-protected Au/Ag nanocages (NCs), i.e., hollow and porous
      metallic nanoparticles, by galvanic replacement reaction. Subsequently, we
      functionalized the NCs with a fluorescent derivative of 4-methoxy-1,8
      naphtalimide (NAFTA6). The plasmonic properties of these structures, which
      exhibit an extinction maximum in the 700-800 nm range, allowed their use as SERS
      active substrates for excitation at 785 nm and an efficient identification of the
      vibrational bands of NAFTA6, in spite of the low ligand concentration (<10(-5)
      M). Furthermore, NAFTA6 could also be identified from its fluorescence emission.
      The proposed functionalization with fluorescent compounds opens the way to the
      application of metal NCs using double-wavelength detection. Namely, Raman
      spectroscopy in the near infrared and fluorescence emission in the visible
      region, with considerable potential especially for in vivo medical applications,
      as the plasmonic band is centered in the visible light region where biological
      fluids and tissues are transparent.

PMID- 23871313
TI  - Associations of depression diagnosis and antidepressant treatment with mortality
      among young and disabled Medicare beneficiaries with COPD.
AB  - OBJECTIVE: Depression is prevalent in chronic obstructive pulmonary disease
      (COPD) patients and a risk factor for COPD exacerbation and death. The objective
      of this study was to determine the associations of depression diagnosis and
      antidepressant treatment with mortality among Social Security Disability
      Insurance (SSDI)-eligible (age <65 years who had permanent physical or mental
      disabilities) Medicare beneficiaries with COPD. METHOD: This retrospective cohort
      study used a 5% random sample of SSDI-eligible Medicare beneficiaries with COPD
      in stand-alone Part D plans during 2006-2008 (n=17,320). COPD and depression
      diagnoses were assessed during 2006. Evidence of antidepressant treatment was
      measured in 2006-2008. All-cause mortality was measured in 2007-2008. Cox
      proportional hazards models were used to examine the associations of depression
      diagnosis with mortality and, among depressed beneficiaries, antidepressant
      treatment (time dependent) with mortality after controlling for covariates.
      RESULTS: More than one third (37.3%) of SSDI-eligible beneficiaries with COPD had
      a baseline depression diagnosis; of those, 86.8% had evidence of antidepressant
      treatment. Baseline depression diagnosis was an independent risk factor for 2
      year mortality [hazard ratio (HR)=1.21; 99% confidence interval (CI)=1.07-1.37].
      Among depressed beneficiaries, receiving antidepressant treatment was associated
      with significantly lower mortality (HR=0.55; 99% CI=0.44-0.68). CONCLUSION:
      Proactive antidepressant treatment should be considered as an intervention to
      reduce mortality for this young and disabled Medicare population.

PMID- 23871314
TI  - Fulminant Clostridium difficile colitis: a complication of perioperative
      antibiotic prophylaxis.
AB  - Antibiotic prophylaxis for maxillofacial surgical wounds remains common practice.
      Surgeons must weigh the risks (e.g., Clostridium difficile colitis) against the
      benefits before administering antibiotics for any reason and the relative risk
      and morbidity of C difficile colitis against those of a potential postoperative
      wound infection. In addition, the possibility of C difficile infection as a
      complication of perioperative antibiotic prophylaxis should be discussed with
      patients before surgery, especially those with concomitant baseline risk factors.
      This report describes the case of a young healthy patient with few risk factors
      for C difficile infection who received a standard perioperative course of
      antibiotic therapy. Subsequently, the patient developed severe fulminant C
      difficile infection that required a protracted hospital admission, subtotal
      colectomy, and ileostomy. This case underscores that antibiotic prophylaxis
      continues in widespread use and is not benign therapy.

PMID- 23871315
TI  - Prognosis for gingival carcinomas with a delayed diagnosis after dental
      extraction.
AB  - PURPOSE: In gingival squamous cell carcinoma (GSCC), the association between
      survival and previous dental extraction (DE) is controversial. The purpose of
      this study was to investigate the prognosis for patients in whom GSCC was
      detected after DE was performed. PATIENTS AND METHODS: DE for GSCC tumor symptoms
      was performed in 19 patients before diagnosis (DE group) and not in 58 patients
      (non-DE group). The clinical features, characteristics, and prognosis were
      evaluated statistically between the 2 groups. RESULTS: The interval from DE to
      the first hospital visit was 1.1 to 97 weeks (median, 7.3 weeks). There was no
      significant difference in tumor status, node status, local recurrence,
      pathologically positive lymph nodes, or distant metastasis between the DE and non
      DE groups. Bone invasion was observed radiographically in 6 patients with
      mandibular GSCC in the DE group (100%) and 13 in the non-DE group (68.4%). There
      was a significant difference in bone invasion between the DE and non-DE groups (P
      < .01). Segmental mandibulectomy was performed in 11 patients (84.6%) in the DE
      group and 21 patients (61.8%) in the non-DE group. Extent of resection tended to
      be larger for the DE group. The 5-year overall survival rate was 84.6% for the DE
      group and 65.8% for patients with mandibular GSCC in the non-DE group. For
      maxillary GSCC, the survival rates differed significantly between groups (33.3%
      in DE group and 73.7% in non-DE group). CONCLUSIONS: For mandibular GSCC, the
      resection field was appropriate for the extent of bone invasion after DE and the
      prognosis was similar to that in the non-DE group. For maxillary GSCC, a broad
      surgical field is suggested because of the potential for rapid spread in
      cancellous bony trabeculae.

PMID- 23871316
TI  - What is in a name? Oral and maxillofacial surgeon versus oral surgeon.
AB  - PURPOSE: In 1975, the American Society of Oral Surgeons officially changed its
      name to the American Association of Oral and Maxillofacial Surgeons. This change
      was intended to address the specialty's expanding surgical scope. However, today,
      many health care professionals continue to use the term oral surgeon. This study
      was undertaken to determine if students' perception of the oral and maxillofacial
      surgeon's (OMS) surgical scope would change when oral and maxillofacial surgeon
      was used instead of oral surgeon. MATERIAL AND METHODS: This cross-sectional
      study surveyed undergraduate and dental students' choice of specialist to treat
      21 different conditions. The independent variable was the specialty term (oral
      and maxillofacial surgeon vs oral surgeon). The dependent variables were
      specialists chosen for the procedure (ear, nose, and throat surgeon; plastic
      surgeon; OMS or oral surgeon; periodontist; other). The test of proportions (z
      test) with the Yates correction was performed for data analysis. RESULTS: Of the
      280 senior dental students who were surveyed, 258 surveys were included in the
      study. Dental students' perception of the OMS's surgical scope increased
      significantly from 51% to 55% when oral and maxillofacial surgeon was used
      instead of oral surgeon. Of the 530 undergraduate upper division science students
      who were surveyed, 488 surveys were included in the study. Undergraduate upper
      division science students' perception of the OMS's surgical scope increased
      significantly from 23% to 31% when oral and maxillofacial surgeon was used as an
      option instead of oral surgeon. CONCLUSION: The use of oral and maxillofacial
      surgeon increased students' perception of the OMS's surgical scope. This study
      also suggested that students were not fully aware of the magnitude of the OMS's
      scope of practice. The current dichotomy and inconsistent use of the specialty's
      official term adds to the confusion and to misunderstanding. Therefore, OMSs
      should universally refer to themselves as oral and maxillofacial surgeons and
      help educate others of their scope.

PMID- 23871317
TI  - Inferior alveolar nerve regeneration after bifocal distraction osteogenesis in
      dogs.
AB  - PURPOSE: Bifocal distraction osteogenesis has been shown to be a reliable method
      for reconstructing missing bone segments. However, no reports have been published
      regarding inferior alveolar nerve regeneration during this procedure. We assumed
      that the nerve could regenerate with the bone regeneration during bifocal
      distraction, if the nerve had been saved at a mesial site of the transport disc.
      In the present study, we investigated that possibility in dogs. MATERIALS AND
      METHODS: Using a bifocal distraction osteogenesis method, we produced a 10-mm
      mandibular defect, including the nerve defect, and distracted the transport disc
      at a rate of 1 mm/day in 12 dogs. The nerve was saved at the mesial site of the
      transport disc. The regenerated nerve was evaluated by a jaw opening reflex
      examination performed once daily. Histologic examinations with hematoxylin-eosin
      and immunohistochemical staining with neurofilament and S-100 antibody were also
      performed on all dogs after death at 3, 6, and 12 months after the first
      operation. RESULTS: The jaw opening reflex had recovered in all dogs. The average
      period of recovery was 109.5 +/- 24.7 days. On histologic examination, although
      consecutive nerves were observed in all areas, cellular nerve fascicles were
      seen, consistent with wallerian degeneration at 3 and 6 months in the nerve
      connection area on the distal side of the transport disc. CONCLUSIONS: Our
      results have indicated that inferior alveolar nerve regeneration after bifocal
      distraction osteogenesis is successful in dogs. Although our research is still at
      the stage of animal experiments, future application in humans can be considered
      to be possible.

PMID- 23871318
TI  - In vivo 3D analysis of clavicular kinematics during scapular plane abduction:
      comparison of dominant and non-dominant shoulders.
AB  - The purpose of this study was to evaluate side-to-side differences in three
      dimensional clavicle kinematics in normal shoulders during dynamic scapular plane
      elevation using model-image registration techniques. Twelve healthy males with a
      mean age of 32 years (range, 27-36 years old) were enrolled in this study.
      Clavicle rotations were computed with bilateral fluoroscopic images and CT
      derived bone models using model-image registration techniques and compared
      between dominant and nondominant shoulders. There was no difference in retraction
      between both shoulders. The clavicle in dominant shoulders was less elevated
      during abduction than in nondominant shoulders (P=0.03). Backward rotation angles
      of dominant shoulders were significantly smaller than those of nondominant
      shoulders throughout the activity (P=0.03). Clavicular kinematics during scapular
      plane abduction were different according to hand-dominance. 

PMID- 23871319
TI  - Kinematic analysis of postural reactions to a posterior translation in rocker
      bottom shoes in younger and older adults.
AB  - Shoes with rocker bottom soles are utilized by persons with diabetic peripheral
      neuropathy to reduce plantar pressures during gait. The risk of falls increases
      with age and is compounded by diabetic neuropathy. The purpose of this study was
      to analyze how rocker bottom shoes affect posture control of older adults (50-75
      years old) and younger adults (20-35 years old) in response to posterior slide
      perturbations. The postural response to a posterior platform translation was
      normalized among subjects by applying the below threshold stepping velocity
      (BTSV) for each subject. The BTSV was the fastest velocity of platform
      translation that did not cause a stepping response while wearing the rocker
      bottom shoes. Joint excursion, time to first response, response time, and
      variability of mean peak joint angles were analyzed at the ankle, knee, hip,
      trunk, and head in the sagittal plane. The statistical analysis was a 2-factor
      mixed repeated measures design to determine interactions between and within shoe
      types and age groups. While wearing rocker bottom shoes, both age groups
      exhibited increased joint excursion, differences in time to initial response, and
      longer response time. The older group demonstrated decreased joint excursion and
      increased time to initial response compared to the younger group, as well as a
      significantly slower mean BTSV. These findings support the conclusion that in
      healthy older adults and in populations at risk for falls, the use of rocker
      bottom or other unstable shoes may increase the potential of falls when
      confronted with a standing perturbation such as a forceful slip or trip. 

PMID- 23871320
TI  - Comparison of laparoscopic common bile duct exploration and endoscopic retrograde
      cholangiopancreatography plus laparoscopic cholecystectomy for
      choledocholithiasis: a prospective randomized study.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography and laparoscopic
      common bile duct exploration are safe and efficient methods that have recently
      been used for the treatment of bile duct stones. The aim of this study was to
      compare the efficacy, safety, and surgical outcomes of the laparoscopic common
      bile duct exploration plus laparoscopic cholecystectomy (LCBDE+LC) and endoscopic
      retrograde cholangiopancreatography plus laparoscopic cholecystectomy (ERCP+LC).
      METHODS: One hundred twenty patients were prospectively randomized into 2 groups:
      LCBDE with LC in a single intervention and LC after ERCP. RESULTS: The success
      rate of the LCBDE+LC group (96.5%) was found to be higher than for the ERCP+LC
      group (94.4%). Complication rates of the LCBDE+LC and ERCP+LC group were 7% and
      11.1%, respectively. Complications requiring ERCP in the postoperative period
      after LCBDE+LC have been noted in 3.5% of cases. CONCLUSIONS: Laparoscopic CBD
      exploration provides an alternative therapeutic approach that has less morbidity,
      is cost-effective, and allows earlier recovery with a reduced period of short
      term disability.

PMID- 23871321
TI  - Circumferential margin plays an independent impact on the outcome of rectal
      cancer patients receiving curative total mesorectal excision.
AB  - BACKGROUND: The aim of this study was to determine the impact of the
      circumferential resection margin on the outcomes of patients with rectal cancer
      undergoing total mesorectal excision. METHODS: Medical records from July 2004 to
      June 2008 were prospectively reviewed, and 348 patients who underwent potentially
      curative surgery for rectal cancer were identified. The influence of the
      circumferential resection margin on local recurrence, distant metastasis, and 5
      year cancer-specific survival was assessed. RESULTS: Of 348 patients, 13 (3.7%)
      had positive circumferential resection margins. During a median follow-up period
      of 58.0 months, 8 patients (2.3%) had local recurrence and 53 (15.2%) developed
      distant metastases. Local recurrence rates and distant metastasis rates in
      patients with positive circumferential resection margins were 15.4% and 61.5%,
      respectively, significantly higher than in those with negative circumferential
      resection margins (1.8% and 13.4%, respectively) (P < .001). The 5-year cancer
      specific survival rates were 75.8% and 0% for patients with tumors having
      negative and positive circumferential resection margins, respectively (P < .001).
      CONCLUSIONS: A circumferential resection margin of <=1 mm adversely affects
      cancer-specific survival, local recurrence, and distant metastasis.

PMID- 23871322
TI  - Feedback activities of instructors during a trauma surgery course.
AB  - BACKGROUND: The aim of this study was to examine the quality and quantity of
      feedback and instruction from faculty members during an acute trauma surgery team
      training using a newly designed observational feedback instrument. METHODS:
      During the training, 11 operating teams, each consisting of 1 instructor coaching
      2 trainees, were videotaped and audiotaped. Forty-five minutes of identical
      operating scenarios were reviewed and analyzed. Using a new observational
      feedback instrument, feedback and instruction, containing different levels of
      specific information related to technical and nontechnical skills, were noted.
      RESULTS: Instructors more often provided instruction (25.8 +/- 10.6 times) than
      feedback (4.4 +/- 3.5 times). Most feedback and instruction contained either
      nonspecific or less specific information and referred to technical skills.
      Instructors addressed communication skills more specifically. CONCLUSIONS:
      Coaching by faculty members predominantly contained unspecific instructions
      regarding technical skills. The observational feedback instrument enabled scoring
      of the coaching activities.

PMID- 23871323
TI  - Reliable assessment of general surgeons' non-technical skills based on video
      recordings of patient simulated scenarios.
AB  - BACKGROUND: Nontechnical skills are essential for safe and efficient surgery. The
      aim of this study was to evaluate the reliability of an assessment tool for
      surgeons' nontechnical skills, Non-Technical Skills for Surgeons dk (NOTSSdk),
      and the effect of rater training. METHODS: A 1-day course was conducted for 15
      general surgeons in which they rated surgeons' nontechnical skills in 9 video
      recordings of scenarios simulating real intraoperative situations. Data were
      gathered from 2 sessions separated by a 4-hour training session. RESULTS:
      Interrater reliability was high for both pretraining ratings (Cronbach's alpha =
      .97) and posttraining ratings (Cronbach's alpha = .98). There was no
      statistically significant development in assessment skills. The D study showed
      that 2 untrained raters or 1 trained rater was needed to obtain generalizability
      coefficients >.80. CONCLUSIONS: The high pretraining interrater reliability
      indicates that videos were easy to rate and Non-Technical Skills for Surgeons dk
      easy to use. This implies that Non-Technical Skills for Surgeons dk (NOTSSdk)
      could be an important tool in surgical training, potentially improving safety and
      quality for surgical patients.

PMID- 23871324
TI  - Hernia repair: why do we continue to perform mesh repair in the face of the human
      toll of inguinodynia?
AB  - Fifteen to 20 years ago, transversalis and Shouldice Hospital repairs were
      standard, with a 4% to 6% rate of recurrence. With a focus on recurrence, various
      mesh repairs were proposed to reduce the incidence of recurrence. With these
      repairs, an increased incidence of inguinodynia due to the entrapment of the
      nerves proximate (adjacent) to the mesh has been observed. Many surgeons doubted
      its existence; however, there is sufficient evidence that with mesh repair in
      which the affected nerves are resected, the incidence of severe pain is lessened
      considerably. Triple neurectomy has been proposed as a therapy, but only 80% of
      patients are relieved of pain. Recurrence is insufficient to make patients' lives
      miserable, with mesh repair reporting up to a 21% incidence of inguinodynia.
      Although few surgeons today perform this procedure and most residents have never
      seen it, the author proposes that mesh repairs be abandoned and the transversalis
      or Shouldice Hospital repair be adopted. 

PMID- 23871325
TI  - Capnography for the nonintubated patient in the emergency setting.
AB  - BACKGROUND: Multiple studies illustrate the benefits of waveform capnography in
      the nonintubated patient. This type of monitoring is routinely used by anesthesia
      providers to recognize ventilation issues. Its role in the administration of deep
      sedation is well defined. Prehospital providers embrace the ease and benefit of
      monitoring capnography. Currently, few community-based emergency physicians
      utilize capnography with the nonintubated patient. OBJECTIVE: This article will
      identify clinical areas where monitoring end-tidal carbon dioxide is beneficial
      to the emergency provider and patient. DISCUSSION: Capnography provides real-time
      data to aid in the diagnosis and patient monitoring for patient states beyond
      procedural sedation and bronchospasm. Capnographic changes provide valuable
      information in such processes as diabetic ketoacidosis, seizures, pulmonary
      embolism, and malignant hyperthermia. CONCLUSIONS: Capnography is a quick, low
      cost method of enhancing patient safety with the potential to improve the
      clinician's diagnostic power.

PMID- 23871326
TI  - Ivermectin causes Cimex lectularius (bedbug) morbidity and mortality.
AB  - BACKGROUND: Bedbug infestations are increasing across North America and Europe,
      with more people presenting to Emergency Departments for treatment. Physicians
      cannot provide substantive treatment for people affected by bedbugs. STUDY
      OBJECTIVE: To determine if ivermectin, a relatively inexpensive and safe, long
      acting oral anti-parasitic drug is able to cause bedbug morbidity and mortality.
      METHODS: We evaluated the effects of ivermectin on bedbugs using an artificial
      feeding membrane and mice and humans. Bedbug morbidity, mortality, and nymph
      molting was recorded. RESULTS: Using an artificial feeding membrane, bedbug
      mortality was 98% (n = 81) for 260 ng/mL ivermectin and 0% for 0 ng/mL ivermectin
      (control; n = 90) after 13 days. Mortality for bedbugs fed on mice injected with
      the human equivalent of 200 MUg/kg ivermectin was 86% (n = 22), vs. 0% in the 0
      MUg/kg ivermectin (control; n = 21). Of the surviving nymphs, 0% exposed to
      ivermectin molted by day 75, vs. 80% in the control group by day 8. Bedbugs that
      fed once on human study subjects 3 h after consuming 200 MUg/kg of oral
      ivermectin had a 63% (n = 24) 20-day mortality rate, vs. 8% (n = 24) in the
      control group. Of the surviving nymphs, 0% (n = 5) in the 3-h ivermectin group
      molted, vs. 80% (n = 10) of the control group. CONCLUSIONS: It may be possible
      that ivermectin could help eradicate, suppress, or prevent a bedbug infestation.

PMID- 23871327
TI  - Ultrasound of the inferior vena cava does not predict hemodynamic response to
      early hemorrhage.
AB  - BACKGROUND: Ultrasonographic evaluation of the inferior vena cava (IVC) provides
      information on central hemodynamics and predicts fluid responsiveness during
      positive pressure ventilation. In spontaneously breathing patients, the
      correlations between IVC dynamics and the hemodynamic response to volume shifts
      remain to be described. OBJECTIVES: We aimed to describe the correlation between
      IVC dynamics and the changes in cardiac output (CO) caused by controlled
      hemorrhage. METHODS: Healthy donors from the blood bank were eligible for
      inclusion. Measurements of the IVC and CO were performed before and immediately
      after blood donation using ultrasound methods. A control group served to evaluate
      the effect of resting. RESULTS: Thirty-seven participants completed the study.
      IVC collapsibility index (IVC-CI) and IVC end expiratory diameter (IVCe) both
      changed significantly after blood donation (p < 0.001). The baseline IVC-CI and
      IVCe did not correlate with the change in CO (p-values >= 0.40). The alterations
      in IVC-CI and IVCe induced by blood donation also did not correlate with the
      change in CO (p >= 0.71). The sensitivities of IVC-CI or IVCe, defined as an
      increase in IVC-CI and a decrease in IVCe, for picking up any decrease in CO were
      81.3% and 84.4%, respectively. In the control group, no effect was seen between
      measurements. CONCLUSION: IVC-CI and IVCe did not correlate with the magnitude of
      hemodynamic response to early hemorrhage. The sensitivity of serial IVC
      measurements was approximately 80% for detecting early blood loss.

PMID- 23871328
TI  - Immediate breast reconstruction with expander in pregnant breast cancer patients.
AB  - BACKGROUND: Breast reconstruction after mastectomy is currently considered an
      essential component in managing breast cancer patients, particularly those
      diagnosed at a young age. However, no studies have been published on the
      feasibility of immediate breast reconstruction in patients diagnosed and operated
      during the course of gestation. METHOD: We retrospectively identified all breast
      cancer patients who were subjected to mastectomy and immediate breast
      reconstruction during pregnancy at the European Institute of Oncology between
      2002 and 2012. Patient demographics, gestational age at surgery, tumor stage,
      adjuvant treatment, details of the surgical procedures, surgical outcomes and
      fetal outcomes were analyzed. RESULTS: A total of 78 patients with breast cancer
      diagnosed during pregnancy were subjected to a surgical procedure during the
      course of gestation. Twenty-two patients had mastectomy; of whom 13 were
      subjected to immediate breast reconstruction. Twelve out of 13 patients had a two
      stage procedure with tissue expander insertion. Median gestational age at surgery
      was 16 weeks. No major surgical complications were encountered. Only one patient
      elected to have an abortion, otherwise, no spontaneous abortions or pregnancy
      complications were reported. Median gestational age at delivery was 35 weeks
      (range: 32-40 weeks). No major congenital malformations were reported. At a
      median follow-up of 32 months, all patients are alive with no long-term surgical
      complications. CONCLUSIONS: This is the first study of immediate breast
      reconstruction in pregnant breast cancer patients. Tissue expander insertion
      appears to ensure a short operative time, and does not seem to be associated with
      considerable morbidity to the patient or the fetus. Hence, it could be considered
      in the multidisciplinary management of women diagnosed with breast cancer during
      pregnancy.

PMID- 23871329
TI  - Baseline artery diameter: the hidden confounder in research syntheses on human
      endothelial function?

PMID- 23871330
TI  - Refractory ascites - a rare presentation of severe aortic regurgitation.
AB  - A 47 year-old male with a history of refractory ascites presented to our centre
      complaining of dyspnoea, abdominal distention, and weight gain. He was admitted
      under a medical team for investigation and management. Work-up excluded all
      common aetiologies of ascites. Echocardiography revealed severe aortic
      regurgitation (AR) with a dilated left ventricle but no right heart pathology or
      pulmonary hypertension. He underwent mechanical aortic valve replacement. Intra
      operatively, a prolapsing left coronary leaflet of the aortic valve with frayed
      edges raised suspicion of resolved infective endocarditis. Postoperative course
      was uneventful. Following replacement of the aortic valve, the patient was
      completely free of ascites. This case demonstrates that ascites can be an unusual
      clinical presentation of severe aortic regurgitation, which may respond to aortic
      valve replacement. 

PMID- 23871331
TI  - Predictors of electroconvulsive therapy postictal delirium.
AB  - BACKGROUND: Postictal delirium is a common adverse effect of electroconvulsive
      therapy (ECT) and can be dangerous to both patient and staff caring for them in
      the postanesthesia care unit. However, little is known about predictors of
      postictal delirium. OBJECTIVES: The aim of this study was to identify predictors
      of postictal delirium. We hypothesized that both patient and ECT treatment
      variables might influence the likelihood of postictal delirium. METHODS: We
      prospectively monitored postictal delirium in the postanesthesia care unit using
      the Confusion Assessment Method for the Intensive Care Unit after the first ECT
      treatment of 96 consecutive patients. Patient and treatment variables were
      extracted retrospectively by chart review. A multiple logistic regression model
      was developed to assess the effect of these variables on the likelihood of
      developing delirium. RESULTS: Seizure length was found to be a statistically
      significant predictor of postictal delirium after adjusting for other covariates
      (p = 0.003). No other variables were predictive. CONCLUSION: A long ECT seizure
      increases the likelihood of delirium in the postanesthesia care unit at the first
      treatment. This finding suggests that postanesthesia care unit staff may benefit
      from knowledge about seizure length for predicting postictal delirium and
      anticipating the best management of post-ECT patients.

PMID- 23871332
TI  - Viscoelastic properties of the human sternocleidomastoideus muscle of aged women
      in relaxation.
AB  - Improving the numerical models of the head and neck complex requires
      understanding the mechanical properties of the muscles; however, most of the data
      in existing literature have been obtained from studies on animal muscles. Muscle
      is hyper-elastic, but also viscoelastic. The hyper-elastic behaviour of the human
      sternocleidomastoideus muscle has been previously studied. The aim of this study
      is to propose a characterization of the viscoelastic properties of the same human
      muscle in relaxation. Ten muscles were tested in vitro. The viscoelastic
      behaviour was modelled with a generalized Maxwell's model studied at the first
      and second order, using an inverse approach with a subject-specific, finite
      element model of each muscle. Based on these models, relaxation times tau (first
      order: 103s; second order: 18s and 395s) and ratio moduli gamma (first order:
      0.33; second order: 0.20 and 0.19) were identified. The first-order model
      provided a good estimate of the relaxation curve (R(2): 0.82), but the second
      order model was more representative of the experimental response (R(2): 0.97).
      Our results provide evidence that the viscoelastic behaviour of the human
      sternocleidomastoideus muscle can be described using a second-order Maxwell's
      model and that - combined with the previously identified hyper-elastic properties
      - the response of the muscle in tension and relaxation is fully characterized. 

PMID- 23871333
TI  - Indicators of heart rate variability, urinary norepinephrine and plasma lipid
      levels in healthy adults.

PMID- 23871334
TI  - Proof of myocardial autophagy by combining antigen retrieval and the avidin
      biotin peroxidase complex method.

PMID- 23871335
TI  - Statins: a sine qua non of the management of patients with abdominal aortic
      aneurysms.

PMID- 23871336
TI  - The "smoker's paradox" in Asian versus non-Asian patients with percutaneous
      coronary intervention longer than 6 months follow-up: a collaborative meta
      analysis with the ET-CHD registry.

PMID- 23871338
TI  - Relationship of maximum and minimum tricuspid valve annular diameter determined
      by 320-slice CT with right atrial and ventricular volume and estimated right
      ventricular systolic pressure.

PMID- 23871337
TI  - Genome-wide linkage analysis of carotid artery lumen diameter: the strong heart
      family study.
AB  - BACKGROUND: A significant proportion of the variability in carotid artery lumen
      diameter is attributable to genetic factors. METHODS: Carotid ultrasonography and
      genotyping were performed in the 3300 American Indian participants in the Strong
      Heart Family Study (SHFS) to identify chromosomal regions harboring novel genes
      associated with inter-individual variation in carotid artery lumen diameter.
      Genome-wide linkage analysis was conducted using standard variance component
      linkage methods, implemented in SOLAR, based on multipoint identity-by-descent
      matrices. RESULTS: Genome-wide linkage analysis revealed a significant evidence
      for linkage for a locus for left carotid artery diastolic and systolic lumen
      diameters in Arizona SHFS participants on chromosome 7 at 120 cM (lod = 4.85 and
      3.77, respectively, after sex and age adjustment, and lod = 3.12 and 2.72,
      respectively, after adjustment for sex, age, height, weight, systolic and
      diastolic blood pressure, diabetes mellitus and current smoking). Other regions
      with suggestive evidence of linkage for left carotid artery diastolic and
      systolic lumen diameter were found on chromosome 12 at 153 cM (lod = 2.20 and
      2.60, respectively, after sex and age adjustment, and lod = 2.44 and 2.16,
      respectively, after full covariate adjustment) in Oklahoma SHFS participants;
      suggestive linkage for right carotid artery diastolic and systolic lumen diameter
      was found on chromosome 9 at 154 cM (lod = 2.72 and 3.19, respectively after sex
      and age adjustment, and lod = 2.36 and 2.21, respectively, after full covariate
      adjustment) in Oklahoma SHFS participants. CONCLUSION: We found significant
      evidence for loci influencing carotid artery lumen diameter on chromosome 7q and
      suggestive linkage on chromosomes 12q and 9q.

PMID- 23871339
TI  - Full neurological recovery, Cerebral Performance Category (CPC) 1, after 65
      minute cardiac arrest using percutaneous cardiopulmonary system and therapeutic
      hypothermia.

PMID- 23871340
TI  - Ticagrelor or prasugrel for pre-hospital protocols in STEMI?

PMID- 23871341
TI  - Incidence of Tako-Tsubo cardiomyopathy in urban agglomerations.

PMID- 23871342
TI  - Predictive ability of self-rated health for adverse events during beta-blocker
      treatment in patients with chronic heart failure.

PMID- 23871343
TI  - Incremental prognostic value of identifying mitral L wave in patients with atrial
      fibrillation.

PMID- 23871344
TI  - The association between hyperuricemia, left atrial size and new-onset atrial
      fibrillation.
AB  - BACKGROUND: Although hyperuricemia was associated with several cardiovascular
      diseases, the role of uric acid (UA) in left atrial (LA) remodeling and new-onset
      atrial fibrillation (AF) has not been fully explored. The goal of the present
      study is to investigate the relationship between UA, LA diameter and the
      development of AF in the large-scale cohort. METHODS: The study consisted of 2
      parts. First, we investigated the association between serum UA and LA diameter in
      a single-center database (n = 3043). Second, we studied and compared the risk of
      new-onset AF among patients with and without hyperuricemia in the nationwide
      longitudinal cohort in Taiwan (n = 122,524). RESULTS: Elevated serum level of UA
      was associated with an increased systemic inflammation, and insulin resistance.
      The LA diameter was significantly correlated with serum UA (r = 0.341, p value <
      0.001). The linear correlation between LA dimension and UA level remained
      significant after the adjustment for clinical, biochemical and echocardiographic
      variables. In the nationwide cohort, there were 2339 patients (1.9% of the study
      population) developing AF during the follow-up of 6.3 +/- 3.0 years. The AF
      occurrence rate was higher in patients with hyperuricemia than those without it
      (2.1% versus 1.7%; p value < 0.001). Hyperuricemia was a significant risk factor
      of new-onset AF with a hazard ratio of 1.191 (95% confidence interval = 1.098
      1.292, p value < 0.001) in the multivariate Cox regression analysis. CONCLUSIONS:
      Hyperuricemia was associated with a larger LA size and may be a novel risk factor
      for the development of AF.

PMID- 23871346
TI  - The number of cardiologists, case volume, and in-hospital mortality in acute
      myocardial infarction patients.

PMID- 23871345
TI  - Angiotensin type 2 receptors in the intermediolateral cell column of the spinal
      cord: negative regulation of sympathetic nerve activity and blood pressure.
AB  - BACKGROUND: Our previous study demonstrated that AT2R in brainstem nuclei
      participated in the regulation of sympathetic outflow and cardiovascular
      function. However, the functional significance of AT2R in the intermediolateral
      cell column (IML) of the thoracic spinal cord in normal rats remains elusive. We
      hypothesized that AT2R activation in the IML exerts a sympatho-inhibitory effect.
      METHODS AND RESULTS: Using Western-blot analysis, immunohistochemical staining
      and quantitative real-time PCR, both AT1R and AT2R expressions were detected in
      the spinal cord. The highest AT2R protein expression was found in the IML, while
      AT1R expression didn't display regional differences within the gray matter.
      Microinjection of Ang II into the IML dose-dependently elevated mean blood
      pressure (MAP, employing a transducer-tipped catheter) and renal sympathetic
      nerve activity (RSNA, using a pair of platinum-iridium recording electrodes),
      which were completely abolished by Losartan, and attenuated by TEMPOL and
      apocynin. Activation of AT2R in the IML with CGP42112 evoked hypotension
      (DeltaMAP: -21 +/- 4 mmHg) and sympatho-inhibition (RSNA: 73 +/- 3% of baseline),
      which were completely abolished by PD123319 and l-NAME. Blockade of AT2R in the
      IML with PD123319 significantly increased MAP (11 +/- 1 mmHg) and sympathetic
      nerve activity (RSNA: 133 +/- 13% of baseline). Moreover, PD123319 significantly
      enhanced the Ang II induced pressor response. Furthermore, in isolated IML
      neurons, CGP42112 treatment augmented potassium current and decreased resting
      membrane potential by employing whole-cell patch clamp. CONCLUSION: In the normal
      condition, AT2R in the IML tonically inhibits sympathetic activity through an
      NO/NOS dependent pathway and subsequent potassium channel activation.

PMID- 23871348
TI  - The relevance of the brain in the diseased heart: role of the suprachiasmatic
      nucleus.

PMID- 23871347
TI  - Laser-targeted ablation of the zebrafish embryonic ventricle: a novel model of
      cardiac injury and repair.
AB  - BACKGROUND: While the adult zebrafish (Danio rerio) heart demonstrates a
      remarkable capacity for self-renewal following apical resection little is known
      about the response to injury in the embryonic heart. METHODS: Injury to the
      beating zebrafish embryo heart was induced by laser using a transgenic zebrafish
      expressing cardiomyocyte specific green fluorescent protein. Changes in ejection
      fraction (EF), heart rate (HR), and caudal vein blood flow (CVBF) assessed by
      video capture techniques were assessed at 2, 24 and 48 h post-laser. Change in
      total and mitotic ventricular cardiomyocyte number following laser injury was
      also assessed by counting respectively DAPI (VCt) and Phospho-histone H3 (VCm)
      positive nuclei in isolated hearts using confocal microscopy. RESULTS: Laser
      injury to the ventricle resulted in bradycardia and mild bleeding into the
      pericardium. At 2 h post-laser injury, there was a significant reduction in
      cardiac performance in lasered-hearts compared with controls (HR 117 +/- 11 vs
      167 +/- 9 bpm, p <= 0.001; EF 14.1 +/- 1.8 vs 20.1 +/- 1.3%, p <= 0.001; CVBF 103
      +/- 15 vs 316 +/- 13 MUms(-1), p <= 0.001, respectively). Isolated hearts showed
      a significant reduction in VCt at 2 h post-laser compared to controls (195 +/- 15
      vs 238 +/- 15, p <= 0.05). Histology showed necrosis and apoptosis (TUNEL assay)
      at the site of laser injury. At 24 h post-laser cardiac performance and VCt had
      recovered fully to control levels. Pretreatment with the cell-cycle inhibitor,
      aphidicolin, significantly inhibited functional recovery of the ventricle
      accompanied by a significant inhibition of cardiomyocyte proliferation.
      CONCLUSIONS: Laser-targeted injury of the zebrafish embryonic heart is a novel
      and reproducible model of cardiac injury and repair suitable for pharmacological
      and molecular studies.

PMID- 23871349
TI  - Low stroke risk after elective cardioversion of atrial fibrillation: an analysis
      of the Flec-SL trial.
AB  - BACKGROUND: Current recommendations for anticoagulation management during
      cardioversion are largely based on historical data and expert consensus. METHODS
      AND RESULTS: To characterize current practice of anticoagulation during and after
      elective cardioversion for AF and the risk of stroke and bleeding events, all
      patients enrolled into the Flec-SL trial were analyzed for stroke/transient
      ischemic attack and major bleeds after cardioversion. Flec-SL (ISRCTN62728743,
      NCT00215774) enrolled 635 patients (mean age 63.7 +/- 10.9, 66% male). 629
      (99.1%) patients received periprocedural anticoagulation, 556 (87.6%) were
      adequately anticoagulated following current recommendations. 202 (31.8%) patients
      underwent transesophageal echocardiography-guided cardioversion. Electrical
      cardioversion was used in 508 patients (80.0%), pharmacological cardioversion in
      127 (20%). Six patients suffered from stroke (n = 5) or transient ischemic attack
      (3 TIAs in 1 patient, event rate 0.9%, 95% CI 0.4-2.1), five others from major
      bleeds (event rate 0.8%, 95% CI 0.3-1.9), consistent with the low reported event
      rates in prior studies. Three strokes occurred in the first 5 days after
      cardioversion. Events were independent of type of cardioversion or the use of TEE
      to exclude thrombi. CONCLUSION: Strokes are rare in this large, prospectively
      followed cohort of patients undergoing cardioversion for AF and receiving
      antithrombotic therapy following local routine. These results support adherence
      to current recommendations for anticoagulation during cardioversion of AF.

PMID- 23871350
TI  - Unfavorable stress management strategies in patients with Tako-Tsubo
      cardiomyopathy (TTC).

PMID- 23871351
TI  - Comment on: Diagnostic accuracy of 320-slice computed tomography angiography for
      detection of coronary artery stenosis: meta-analysis (Int J Cardiol 2013,
      http://dx.doi.org/10.1016/j.ijcard.2013.03.023).

PMID- 23871352
TI  - Left atrium in cor triatriatum: arrhythmogenesis and thrombogenesis leading to
      stroke.

PMID- 23871353
TI  - Tbx20 functions as an important regulator of estrogen-mediated cardiomyocyte
      protection during oxidative stress.
AB  - BACKGROUND: As a transcription factor mainly expressed in cardiovascular system,
      T-box 20 (Tbx20) plays an important role in embryonic cardiovascular system
      development and adult heart function. Here, we determined the mechanism by which
      Tbx20 regulates cardiomyocyte apoptosis and cardiomyopathies. METHODS: We
      analyzed Tbx20 expression levels and apoptosis rates in normal and heart failure
      human autopsy heart samples. Female C57BL/6 mice were ovariectomized and treated
      with 17beta-estradiol to determine Tbx20 expression levels. ROS production,
      TUNEL, DNA laddering, qRT-PCR, Western blot, immunohistochemistry and ChIP
      analyses were performed on male C57BL/6 transverse aortic constriction-induced
      heart failure samples and on neonatal rat ventricular myocytes that were treated
      with H2O2 to investigate the role of Tbx20 in estrogen-mediated heart protection.
      RESULTS: Tbx20 expression was down regulated during heart failure, accompanied by
      elevated cardiomyocyte apoptotic levels in humans and mice. H2O2 led to a
      concurrent decrease in Tbx20 expression and increase in apoptosis in cultured
      neonatal rat cardiomyocytes. Tbx20 overexpression reduced H2O2-induced
      cardiomyocyte apoptosis and was associated with a profound inhibition of p38MAPK,
      Bax and caspase3 and the activation of Bcl-2. Estrogen was able to protect
      cardiomyocytes from H2O2-induced apoptosis by upregulating Tbx20 expression in a
      concentration-dependent manner. Tbx20 silencing increased oxidative stress
      induced apoptosis in H9c2 cells. Moreover, Tbx20 directly regulated Esrra
      expression to enhance the heart-protective effect of estrogen. CONCLUSIONS: These
      results indicate that Tbx20 functions as an important regulator of estrogen
      mediated cardiomyocyte protection during oxidative stress, suggesting that
      estorgen-Tbx20-ERR-alpha may represent a crucial regulatory cascade and a
      potential therapeutic target for heart failure.

PMID- 23871354
TI  - Gender differences in characteristics, management and outcome at discharge and
      three months after stroke in a national acute stroke registry.
AB  - BACKGROUND: The importance of gender as an independent risk factor for poor
      outcome is not clear. We examined gender differences in patients' characteristic,
      management and outcome at discharge and 3-months after acute stroke in a national
      hospital-based registry. METHODS: Data were derived from the triennial two-month
      national Acute Stroke Israeli Registry (Feb-March 2004, March-April 2007, April
      May 2010). Unselected patients in all Israeli hospitals (n = 28) were included.
      Outcome at 3-month was assessed in a sub-sample. Logistic regression models were
      used in the study of gender as an independent risk factor for poor outcome.
      RESULTS: In total, 5034 patients (88.5% ischemic stroke, 9.6% ICH and 1.9%
      undetermined stroke) were included, of them 2285 (45.4%) women. Follow-up at 3
      month was completed for 1040 patients, 41.9% women. Women showed higher rates of
      cardiovascular risk factors in-hospital death (p = 0.007) and poor functional
      outcome (p < 0.0001). Following adjustment for age, prior disability, NIHSS,
      prior stroke and risk factors, risk estimates (ORs, 95%CI) for women compared to
      men were 0.72 (0.55-0.96) for in-hospital death, 1.03 (0.83-1.29) for discharge
      to a nursing home or death, and 1.01 (0.86-1.20) for disability. Poor outcomes at
      3-month were significantly more common in women; however, adjusted risk estimates
      were not significantly increased: OR 0.95 (95%CI 0.50-1.81) for death at 3
      months, 1.41 (0.99-2.01) for Barthel Index <= 60, 1.24 (0.90-1.72) for dependency
      and 0.88 (0.55-1.39) for living in a nursing home or death. CONCLUSION: Gender
      differences in risk of death and poor functional outcome after stroke are mainly
      explained by dissimilarities in patients' characteristics and stroke severity.

PMID- 23871355
TI  - Emergency medical service utilization and door-to-balloon time for HIV-infected
      individuals with ST-elevation myocardial infarction.

PMID- 23871356
TI  - Acute myocardial infarction and anagrelide.

PMID- 23871357
TI  - Effect of biomarkers on cardiovascular disease events with special emphasis on
      ethnicity.

PMID- 23871358
TI  - Immunotherapeutic strategies for relapse control in acute myeloid leukemia.
AB  - Despite that the initial phases of chemotherapy induce disappearance of leukemic
      cells in many patients with acute myeloid leukemia (AML), the prevention of life
      threatening relapses in the post-remission phase remains a significant clinical
      challenge. Allogeneic bone marrow transplantation, which is available for a
      minority of patients, efficiently prevents recurrences of leukemia by inducing
      immune-mediated elimination of leukemic cells, and over the past decades,
      numerous immunotherapeutic protocols have been developed aiming to mimic the
      graft-versus-leukemia reaction for the prevention of relapse. Here we review past
      and present strategies for relapse control with focus on overcoming leukemia
      related immunosuppression in AML. We envisage future treatment protocols, in
      which systemic immune activators, such as vaccines, dendritic cell-based
      therapies, engineered variants of IL-2, or IL-15, are combined with agents that
      counter immunosuppression mediated by, e.g., the PD/PDL interaction, CTLA-4,
      CD200, reactive oxygen species, IDO expression, CXCR4, or the KIR/class I
      interaction, based on characteristics of the prevailing malignant clone. This
      combinatorial approach may pave the way for individualized immunotherapy in AML. 

PMID- 23871359
TI  - Review of bowel dysfunction of rectal cancer patients during the first five years
      after sphincter-preserving surgery: a population in need of nursing attention.
AB  - PURPOSE: The aim of the review was to summarize the longitudinal changes in bowel
      dysfunction among patients with rectal cancer within the first five years
      following sphincter-preserving resection. METHODS: A series of literature
      searches were conducted on six English-language electronic databases. Articles
      published after 1990 were searched. A total of 29 articles (reporting 27 studies)
      was found. RESULTS: Bowel dysfunction, including an alteration in the frequency
      of bowel movements, incontinence, abnormal sensations, and difficulties with
      evacuation, is reported among patients with rectal cancer within the first five
      years after sphincter-preserving resection. These problems are most frequent and
      severe within the first year, especially within the first six months, and
      stabilize after one year. Some of the problems may last for years. CONCLUSION:
      Supportive care for bowel dysfunction is needed, and should include the provision
      of information and psychological support delivered in multiple steps. Oncology
      nurses can play an important role in providing supportive care for rectal cancer
      patients with bowel dysfunction.

PMID- 23871360
TI  - Long-term follow-up on continuous intrathecal Baclofen therapy in non-ambulant
      children with intractable spastic Cerebral Palsy.
AB  - BACKGROUND: Little is known about the long-term effects of Continuous intrathecal
      Baclofen (CITB) therapy in non-ambulant children with intractable spastic
      Cerebral Palsy (CP). AIM: To determine whether short-term beneficial effects of
      CITB therapy are present at the long-term, and whether caregivers would choose
      CITB therapy for their child again considering the advantages and disadvantages
      encountered over the years. METHODS: Long-term follow-up data were obtained of
      the children whom had previously participated in a RCT on CITB by the Dutch Study
      Group on Spasticity. Quality of life (QoL) was assessed by the Child Health
      Questionnaire (CHQ), current satisfaction with CITB was measured by use of a
      Visual Analogue Scale regarding previously set treatment goals, functioning in
      daily living was determined by a questionnaire concerning functioning of the
      child, and possible detrimental effects of CITB therapy encountered over the
      years were noted. All data were acquired via interview of the caregivers.
      RESULTS: All 17 children of the former trial participated in this study.
      Previously identified significant positive effects on pain (CHQ 46.8 vs. 74.38, p
      = 0.002; VAS 2.4 vs. 8.01, p = 0.02), ease of care (VAS 2.0 vs. 7.26, p = 0.00),
      and mental health (CHQ 67.2 vs. 75.94, p = 0.010) were still present at the end
      of the trial. Novel significant positive effects were noted at six to nine years
      follow-up, i.e. significantly improved scores on the Parent Impact - Emotional
      subscale (CHQ 66.0 vs. 78.2, p = 0.008), Parent Impact - Time subscale (CHQ 68.9
      vs. 91.72, p = 0.002), and the Physical Summary (CHQ 17.6 vs. 27.4, p = 0.019)
      compared to baseline. Ninety-four percent of the caregivers would choose CITB
      treatment again for their child again. CONCLUSION: The beneficial effects of CITB
      are present at the long term and caregiver satisfaction is high.

PMID- 23871361
TI  - Consecutive 15 min is necessary for focal low frequency stimulation to inhibit
      amygdaloid-kindling seizures in rats.
AB  - Low-frequency stimulation (LFS) is emerging as a new option for the treatment of
      intractable epilepsy. The stimulation duration may influence the anti-epileptic
      effect of LFS but is poorly studied. The present study was designed to evaluate
      the anti-epileptic effect of focal LFS with different stimulation duration on
      amygdaloid-kindling seizures in rats. We found 15 and 30 min but not 1 or 5 min
      LFS delivered immediately after the kindling stimulation slowed the progression
      of behavioral seizure stages and reduced mean afterdischarge duration (ADD)
      during kindling acquisition. In fully kindled animals, 15 and 30min rather than 1
      and 5 min LFS decreased the incidence of generalized seizures and the average
      seizure stage as well as shortened the cumulative generalized seizure duration
      (GSD). Meanwhile, EEG analysis showed 15 and 30 min LFS specifically lowered the
      power in delta band. However, if 15min LFS delivered intermittently by 5 min
      interval, it had no suppressing effect on kindling rat. Thus, it is likely that
      consecutive 15 min is necessary for LFS to inhibit amygdaloid-kindling seizures
      in rats, indicating the stimulation duration may be a key fact affecting the
      clinical effect of LFS on epilepsy.

PMID- 23871362
TI  - Comparison of embryo transfer strategies and assisted reproduction outcome in
      Slovenian and cross-border patients.
AB  - A reduction in the number of embryos transferred is the most important step in
      decreasing multiple gestation rates after medically assisted reproduction.
      Slovenia has implemented insurance company regulations that regulate single
      embryo transfer in selected good-prognosis couples. The aim of the present study
      was to evaluate its effects on the Slovenian population compared with cross
      border patients, who are not affected by the insurance company policy.
      Ultimately, 2403 couples undergoing IVF or intracytoplasmic sperm injection were
      included in the retrospective analysis. Patients were classified according to
      their origin. The decision about the number of embryos transferred and the
      treatment success were evaluated. The implementation of the policy favouring
      single-embryo transfer resulted in a significant decrease in the twin birth rate
      in Slovenian patients (24.4% before policy versus 6.7% after policy
      implementation, P<0.001). Although in cross-border patients twin birth rates have
      declined through the study period, they remained significantly higher compared
      with Slovenian patients (23.1% versus 6.7%, P<0.001). The data demonstrate that
      insurance company policies favouring single-embryo transfer are an effective tool
      in decreasing multiple gestation rates. Similar mechanisms should be implemented
      in the cross-border patient population.

PMID- 23871363
TI  - Mapping men's anticipations and experiences in the reproductive realm:
      (in)fertility journeys.
AB  - This paper examines men's experiences of fertility/infertility against a backdrop
      of changing understandings of men's role in society and medical possibilities. It
      presents findings from two qualitative research projects on men's experiences of
      engagement with reproductive health services as they sought to become fathers and
      anticipate impending fatherhood. The findings from both projects provide insights
      into men's experiences of (in)fertility and their engagement with services set
      against cultural ideals of masculinity. Discussions of reproduction have
      historically focused most centrally upon women's bodies and maternal processes,
      leaving little space for consideration of men's experiences and perspectives.
      While women's experiences of infertility/fertility have been characterized in
      relation to productive or faulty biological processes, male infertility has been
      largely invisible and male fertility typically assumed. This context provides a
      difficult terrain for men in which to contemplate the potential of not being able
      to father a child. The findings discussed in this paper illuminate the ways in
      which men talk about and make sense of their reproductive journeys. In doing so,
      it challenges current understandings of masculinity and reproductive bodies and
      highlights the need to rethink how men are treated in reproductive spheres and
      how services to men are delivered.

PMID- 23871364
TI  - Where are all the men? The marginalization of men in social scientific research
      on infertility.
AB  - There is a wealth of research exploring the psychological consequences of
      infertility and assisted reproduction technology, a substantial body of
      sociological and anthropological work on 'reproductive disruptions' of many kinds
      and a small but growing literature on patient perspectives of the quality of care
      in assisted reproduction. In all these fields, research studies are far more
      likely to be focused on the understandings and experiences of women than those of
      men. This paper discusses reasons for the relative exclusion of men in what has
      been called the 'psycho-social' literature on infertility, comments on research
      on men from psychological and social perspectives and recent work on the quality
      of patient care, and makes suggestions for a reframing of the research agenda on
      men and assisted reproduction. Further research is needed in all areas,
      including: perceptions of infertility and infertility treatment seeking;
      experiences of treatment; information and support needs; decisions to end
      treatment; fatherhood post assisted conception; and the motivation and
      experiences of sperm donors and men who seek fatherhood through surrogacy or co
      parenting. This paper argues for multimethod, interdisciplinary research that
      includes broader populations of men which can contribute to improved clinical
      practice and support for users of assisted reproduction treatment.

PMID- 23871365
TI  - Male coping with cancer-fertility issues: putting the 'social' into
      biopsychosocial approaches.
AB  - Biopsychosocial approaches in infertility and cancer services and research pay
      limited attention to 'social dimensions'. Additionally, existing cancer-related
      male infertility research is dominated by sperm banking studies even though
      fertility-related social concerns in the long term are reported to have an
      adverse effect on wellbeing. This paper considers whether social influences
      affected the fertility-related experiences of 28 men interviewed as part of a
      mixed-gender qualitative study of 'South Asian' and 'White' cancer survivors and
      their professional carers. Findings are reported under: managing stigma;
      sexuality and virility; ambiguity in fertile status; relationship to sperm; and
      meaning of fatherhood. Gender and other social influences were ambiguous, fluid
      and subtle--yet powerful. Combinations were neither standard nor static,
      indicating the dangers of practitioners stereotyping, and/or assuming homogeneity
      of, (in)fertile men and being unaware of their own socialized expectations.
      Social structures and attitudes towards valued male social roles as well as the
      men's psychological capacity and bodily state appear to affect experience. Men
      may more readily be engaged if practitioners proactively attend to the impact of
      social concerns, including employment and financial matters, on their perceived
      capacity to be fathers as a route into raising issues of sexuality and fertility.

PMID- 23871366
TI  - Interaction between dietary content of protein and sodium chloride on milk urea
      concentration, urinary urea excretion, renal recycling of urea, and urea transfer
      to the gastrointestinal tract in dairy cows.
AB  - Dietary protein and salt affect the concentration of milk urea nitrogen (MUN; mg
      of N/dL) and the relationship between MUN and excretion of urea nitrogen in urine
      (UUN; g of N/d) of dairy cattle. The aim of the present study was to examine the
      effects of dietary protein and sodium chloride (NaCl) intake separately, and
      their interaction, on MUN and UUN, on the relationship between UUN and MUN, on
      renal recycling of urea, and on urea transfer to the gastrointestinal tract.
      Twelve second-parity cows (body weight of 645+/-37 kg, 146+/-29 d in milk, and a
      milk production of 34.0+/-3.28 kg/d), of which 8 were previously fitted with a
      rumen cannula, were fitted with catheters in the urine bladder and jugular vein.
      The experiment had a split-plot arrangement with dietary crude protein (CP)
      content as the main plot factor [116 and 154 g of CP/kg of dry matter (DM)] and
      dietary NaCl content as the subplot factor (3.1 and 13.5 g of Na/kg of DM). Cows
      were fed at 95% of the average ad libitum feed intake of cows receiving the low
      protein diets. Average MUN and UUN were, respectively, 3.90 mg of N/dL and 45 g
      of N/d higher for the high protein diets compared with the low protein diets.
      Compared with the low NaCl diets, MUN was, on average, 1.74 mg of N/dL lower for
      the high NaCl diets, whereas UUN was unaffected. We found no interaction between
      dietary content of protein and NaCl on performance characteristics or on MUN,
      UUN, urine production, and renal clearance characteristics. The creatinine
      clearance rate was not affected by dietary content of protein and NaCl. Urea
      transfer to the gastrointestinal tract, expressed as a fraction of plasma urea
      entry rate, was negatively related to dietary protein, whereas it was not
      affected by dietary NaCl content. We found no interaction between dietary protein
      and NaCl content on plasma urea entry rate and gastrointestinal urea entry rate
      or their ratio. The relationship between MUN and UUN was significantly affected
      by the class variable dietary NaCl content: UUN=-17.7+/-7.24 + 10.09+/-1.016 *
      MUN + 2.26+/-0.729 * MUN (for high NaCl); R(2)=0.85. Removal of the MUN * NaCl
      interaction term lowered the coefficient of determination from 0.85 to 0.77. In
      conclusion, dietary protein content is positively related to MUN and UUN, whereas
      dietary NaCl content is negatively correlated to MUN but NaCl content is not
      related to UUN. We found no interaction between dietary protein and NaCl content
      on performance, MUN, UUN, or renal urea recycling, nor on plasma urea entry rate
      and urea transfer to the gastrointestinal tract. For a proper interpretation of
      the relationship between MUN and UUN, the effect of dietary NaCl should be taken
      into account, but we found no evidence that the effect of dietary NaCl on MUN is
      dependent on dietary protein content.

PMID- 23871367
TI  - Proteomic comparison of the probiotic bacterium Lactobacillus casei Zhang
      cultivated in milk and soy milk.
AB  - Soy milk is regarded as a substitute for milk and has become popular in varied
      diets throughout the world. It has been shown that a newly characterized
      probiotic bacterium (Lactobacillus casei Zhang) actually grows faster in soy milk
      than in bovine milk. To elucidate the mechanism involved, we carried out a
      proteomic analysis to characterize bacterial proteins that varied upon growth in
      soy milk and bovine milk at 3 different growth phases, and compare their
      expression under these conditions. A total of 104 differentially expressed spots
      were identified from different phases using a peptide mass fingerprinting assay.
      Functional analysis revealed that a major part of these identified proteins is
      associated with transport and metabolism of carbohydrates, nucleotides, and amino
      acids as well. The results from our proteomic analysis were clarified by real
      time quantitative PCR assay, which showed that Lb. casei Zhang loci involved in
      purine and pyrimidine biosynthesis were transcriptionally enhanced during growth
      in soy milk at lag phase (pH 6.4), whereas the loci involved in carbohydrate
      metabolism were upregulated in bovine milk. Particularly, our results showed that
      l-glutamine might play an important role in the growth of Lb. casei Zhang in soy
      milk and bovine milk, perhaps by contributing to purine, pyrimidine, and amino
      sugar metabolism. 

PMID- 23871368
TI  - Acceptance of sugar reduction in flavored yogurt.
AB  - To investigate what level of sugar reduction is accepted in flavored yogurt, we
      conducted a hedonic test focusing on the degree of liking of the products and on
      optimal sweetness and aroma levels. For both flavorings (strawberry and coffee),
      consumers preferred yogurt containing 10% added sugar. However, yogurt containing
      7% added sugar was also acceptable. On the just-about-right scale, yogurt
      containing 10% sugar was more often described as too sweet compared with yogurt
      containing 7% sugar. On the other hand, the sweetness and aroma intensity for
      yogurt containing 5% sugar was judged as too low. A second test was conducted to
      determine the effect of flavoring concentration on the acceptance of yogurt
      containing 7% sugar. Yogurts containing the highest concentrations of flavoring
      (11% strawberry, 0.75% coffee) were less appreciated. Additionally, the largest
      percentage of consumers perceived these yogurts as "not sweet enough." These
      results indicate that consumers would accept flavored yogurts with 7% added sugar
      instead of 10%, but 5% sugar would be too low. Additionally, an increase in
      flavor concentration is undesirable for yogurt containing 7% added sugar. 

PMID- 23871369
TI  - Effects of chestnut tannins on performance and antioxidative status of transition
      dairy cows.
AB  - This study was conducted to evaluate the effects of chestnut tannins (CT) on
      performance and antioxidative status of transition dairy cows. Twenty multiparous
      Chinese Holstein cows in late gestation were paired according to expected calving
      date and randomly assigned either to a diet supplemented with CT (CNT, 10 g of
      CT/kg of diet, dry matter basis) or to an unsupplemented control (CON) diet from
      3 wk prepartum to 3 wk postpartum. Blood samples were taken on d -21, 1, 7, and
      21 relative to calving for analysis of superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde
      (MDA). Liver samples were taken by puncture biopsy on d 1 and 21 relative to
      calving for analysis of SOD, GSH-Px, and MDA. Data were analyzed for a completely
      randomized block design with repeated measures. The addition of CT had no
      significant effects on dry matter intake, body weight, body condition score, milk
      yield, 3.5% fat-corrected milk yield, and milk composition but did decrease milk
      MDA and somatic cell score in transition dairy cows. Dry matter intake decreased
      from d -21 to 0 and increased from d 1 to 21 relative to calving across
      treatments. During the experimental period, body weight and body condition score
      decreased, whereas milk MDA and somatic cell score increased across treatments. A
      time effect was also observed for plasma MDA, which peaked on d 1 relative to
      calving and remained higher than that on d -21 relative to calving across
      treatments. Addition of CT decreased MDA concentrations in plasma and liver.
      Neither time nor CT * time effects were observed for SOD and T-AOC in plasma and
      SOD and GSH-Px in liver; a time effect was observed for plasma GSH-Px, which
      peaked on d 1 relative to calving and remained higher than those on d -21
      relative to calving across treatments. Addition of CT increased SOD, GSH-Px, and
      T-AOC activities in plasma and SOD and GSH-Px activities in liver. In conclusion,
      addition of CT might inhibit lipid peroxidation and increase antioxidant enzymes
      activities in plasma and liver of transition dairy cows. Supplementation of CT
      may be a feasible means to improve the antioxidative status of transition dairy
      cows.

PMID- 23871370
TI  - Genetic variants of bovine beta- and kappa-casein result in different
      immunoglobulin E-binding epitopes after in vitro gastrointestinal digestion.
AB  - Immunoglobulin E-mediated allergy to cow milk is a common allergy in
      industrialized countries, mainly affecting young children and infants. beta
      Casein (CN) and kappa-CN belong to the major allergens in cow milk. Within these
      milk proteins, genetic polymorphisms occur, which are characterized by
      substitutions or deletions of AA, resulting in different variants for each
      protein. Until now, these variants have not been considered when discussing the
      allergenic potential of bovine milk. In this study, the focus was placed on the
      arising peptide pattern after in vitro gastrointestinal digestion of several beta
      and kappa-CN variants to determine resistant fragments containing IgE-binding
      epitopes and to identify potential differences between these variants. beta
      Casein A(1), A(2), and B, as well as kappa-CN A, B, and E, were separated and
      isolated from milk of cows homozygous for these variants and digested with an in
      vitro gastrointestinal digestion model. The resulting peptides were identified
      using mass spectrometry and compared with previously determined epitopes. Seven
      beta-CN and 4 kappa-CN peptides, common in all beta- or kappa-CN variants,
      remained of sufficient size to harbor IgE-binding epitopes. In addition, some
      peptides and, consequently, epitopes differ from each other due to the AA
      substitution occurring in the individual variants. The distinct peptides AA 108
      to 129 of beta-CN A(1) and A(2), AA 103 to 123 of beta-CN B, as well as AA 59 to
      72, AA 59 to 80, and AA 58 to 80 of all 3 beta-CN variants correspond to the IgE
      binding epitopes AA 107 to 120 and AA 55 to 70, respectively. In kappa-CN, the 2
      variant-specific peptides AA 136 to 149 (kappa-CN A, E) and AA 134 to 150 (kappa
      CN B) are congruent with the IgE-binding epitope AA 137 to 148. The present study
      shows that genetic polymorphisms affected the arising peptide pattern of the
      caseins and thus modifications in the IgE-binding epitopes occurred. As a
      consequence, the casein variants could show differences in their allergenicity.
      Studies investigating the allergenic potential of these different peptides are
      currently in progress. 

PMID- 23871371
TI  - Comparison of functional properties of 34% and 80% whey protein and milk serum
      protein concentrates.
AB  - This study compared the functional properties of serum protein concentrate (SPC)
      with whey protein concentrate (WPC) made from the same milk and with commercial
      WPC. The experimental SPC and WPC were produced at 34% or 80% protein from the
      same lot of milk. Protein contents of WPC and SPC were comparable; however, fat
      content was much lower in SPC compared with WPC and commercial WPC. The effect of
      drying methods (freeze vs. spray drying) was studied for 34% WPC and SPC. Few
      differences due to drying method were found in turbidity and gelation; however,
      drying method made a large difference in foam formation for WPC but not SPC.
      Between pH 3 and 7, SPC was found to have lower turbidity than WPC; however,
      protein solubility was similar between SPC and WPC. Foaming and gelation
      properties of SPC were better than those of WPC. Differences in functional
      properties may be explained by differences in composition and extent of
      denaturation or aggregation. 

PMID- 23871372
TI  - Genetic variance in micro-environmental sensitivity for milk and milk quality in
      Walloon Holstein cattle.
AB  - Animals that are robust to environmental changes are desirable in the current
      dairy industry. Genetic differences in micro-environmental sensitivity can be
      studied through heterogeneity of residual variance between animals. However,
      residual variance between animals is usually assumed to be homogeneous in
      traditional genetic evaluations. The aim of this study was to investigate genetic
      heterogeneity of residual variance by estimating variance components in residual
      variance for milk yield, somatic cell score, contents in milk (g/dL) of 2 groups
      of milk fatty acids (i.e., saturated and unsaturated fatty acids), and the
      content in milk of one individual fatty acid (i.e., oleic acid, C18:1 cis-9), for
      first-parity Holstein cows in the Walloon Region of Belgium. A total of 146,027
      test-day records from 26,887 cows in 747 herds were available. All cows had at
      least 3 records and a known sire. These sires had at least 10 cows with records
      and each herd * test-day had at least 5 cows. The 5 traits were analyzed
      separately based on fixed lactation curve and random regression test-day models
      for the mean. Estimation of variance components was performed by running
      iteratively expectation maximization-REML algorithm by the implementation of
      double hierarchical generalized linear models. Based on fixed lactation curve
      test-day mean models, heritability for residual variances ranged between 1.01*10(
      3) and 4.17*10(-3) for all traits. The genetic standard deviation in residual
      variance (i.e., approximately the genetic coefficient of variation of residual
      variance) ranged between 0.12 and 0.17. Therefore, some genetic variance in micro
      environmental sensitivity existed in the Walloon Holstein dairy cattle for the 5
      studied traits. The standard deviations due to herd * test-day and permanent
      environment in residual variance ranged between 0.36 and 0.45 for herd * test-day
      effect and between 0.55 and 0.97 for permanent environmental effect. Therefore,
      nongenetic effects also contributed substantially to micro-environmental
      sensitivity. Addition of random regressions to the mean model did not reduce
      heterogeneity in residual variance and that genetic heterogeneity of residual
      variance was not simply an effect of an incomplete mean model. 

PMID- 23871373
TI  - Periparturient dairy cows do not exhibit hepatic insulin resistance, yet adipose
      specific insulin resistance occurs in cows prone to high weight loss.
AB  - The periparturient period in dairy cows is associated with alterations in insulin
      action in peripheral tissues; however, the molecular mechanism underlying this
      process is not completely understood. The objective was to examine the response
      to a glucose tolerance test (GTT) and to analyze insulin signaling in liver and
      adipose tissues in pre- and postpartum dairy cows. Liver and adipose tissue
      biopsies were taken before and after GTT, at 17d prepartum and again at 3 to 5d
      postpartum from 8 high-yielding Israeli Holstein dairy cows. Glucose clearance
      rate after GTT was similar pre- and postpartum. Basal insulin concentrations and
      the insulin response to GTT were approximately 4-fold higher prepartum than
      postpartum. In accordance, phosphorylation of the hepatic insulin receptor after
      GTT was higher prepartum than postpartum. Across periods, a positive correlation
      was observed between the basal and peak plasma insulin and phosphorylated insulin
      receptor after GTT in the liver. Hepatic phosphorylation of protein kinase B
      after GTT was elevated pre- and postpartum. Conversely, in adipose tissue,
      phosphorylation of protein kinase B after GTT pre- and postpartum was increased
      only in 4 out of 8 cows that lost less body weight postpartum. Our results
      demonstrate that hepatic insulin signaling is regulated by plasma insulin
      concentrations as part of the homeorhetic adjustments toward calving, and do not
      support a model of hepatic insulin resistance in periparturient cows.
      Nevertheless, we suggest that specific insulin resistance in adipose tissue
      occurs pre- and postpartum only in cows prone to high weight loss. The different
      responses among these cows imply that genetic background may affect insulin
      responsiveness in adipose tissue pre- and postpartum. 

PMID- 23871374
TI  - Casein hydrolysis by Bifidobacterium longum KACC91563 and antioxidant activities
      of peptides derived therefrom.
AB  - Milk protein is a well-known precursor protein for the generation of bioactive
      peptides using lactic acid bacteria. This study investigated the antioxidant
      activity of bovine casein hydrolysate after fermentation with Bifidobacterium
      longum KACC91563 using the 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)
      (ABTS) assay and total phenolic content (TPC). The antioxidant activities of the
      24-h and 48-h hydrolysates were higher than that of the 4-h hydrolysate (2,045.5
      and 1,629.3 MUM gallic acid equivalents, respectively, vs. 40.3 MUM) in the ABTS
      assay. In contrast, TPC values showed activities of 43.2 and 52.4 MUM gallic acid
      equivalents for the 4-h and 24-h hydrolysates, respectively. Three fractions
      (>=10 kDa, >=3 but <10 kDa, and <3 kDa) were separated from the 24-h hydrolysate
      by ultrafiltration. Among these fractions, the <3 kDa fraction exhibited the
      highest antioxidant activity (936.7 MUM) compared with the other fractions (42.1
      and 34.2 MUM for >10 kDa and 3-10 kDa fractions, respectively). Through liquid
      chromatography-electrospray ionization-tandem mass spectrometry analysis, 2
      peptides, VLSLSQSKVLPVPQK and VLSLSQSKVLPVPQKAVPYPQRDMPIQA, containing the
      fragment VLPVPQ that has antioxidant properties, were identified in the <3kDa
      fraction after 24h of hydrolysis. The present study demonstrates the possibility
      of antioxidant peptide production from bovine casein using Bifidobacterium
      longum.

PMID- 23871375
TI  - Investigating the effect of two methane-mitigating diets on the rumen microbiome
      using massively parallel sequencing.
AB  - Variation in the composition of microorganisms in the rumen (the rumen
      microbiome) of dairy cattle (Bos taurus) is of great interest because of possible
      links to methane emission levels. Feed additives are one method being
      investigated to reduce enteric methane production by dairy cattle. Here we report
      the effect of 2 methane-mitigating feed additives (grapemarc and a combination of
      lipids and tannin) on rumen microbiome profiles of Holstein dairy cattle. We used
      untargeted (shotgun) massively parallel sequencing of microbes present in rumen
      fluid to generate quantitative rumen microbiome profiles. We observed large
      effects of the feed additives on the rumen microbiome profiles using multiple
      approaches, including linear mixed modeling, hierarchical clustering, and
      metagenomic predictions. The effect on the fecal microbiome profiles was not
      detectable using hierarchical clustering, but was significant in the linear mixed
      model and when metagenomic predictions were used, suggesting a more subtle effect
      of the diets on the lower gastrointestinal microbiome. A differential
      representation analysis (analogous to differential expression in RNA sequencing)
      showed significant overlap in the contigs (which are genome fragments
      representing different microorganism species) that were differentially
      represented between experiments. These similarities suggest that, despite the
      different additives used, the 2 diets assessed in this investigation altered the
      microbiomes of the samples in similar ways. Contigs that were differentially
      represented in both experiments were tested for associations with methane
      production in an independent set of animals. These animals were not treated with
      a methane-mitigating diet, but did show substantial natural variation in methane
      emission levels. The contigs that were significantly differentially represented
      in response to both dietary additives showed a significant enrichment for
      associations with methane production. This suggests that these methane-mitigating
      diets have altered the rumen microbiome toward naturally low methane-emitting
      microbial profiles. The contig sequences are predominantly new and include
      Faecalibacterium spp. The contigs we have identified here are potential
      biomarkers for low-methane-emitting cattle. 

PMID- 23871376
TI  - Estimation of genetic parameters for individual udder quarter milk content traits
      in Brown Swiss cattle.
AB  - The aim of this study was to estimate genetic parameters and accuracies of
      breeding values for milk content traits of individual udder quarters in Brown
      Swiss cattle. Data of 1,799 phenotyped cows from 40 Swiss dairy herds were
      analyzed, taking the complete pedigree into account. Fat, protein, lactose, and
      urea contents, somatic cell score (SCS), and information about hyperkeratosis
      were available for each udder quarter. The milk of rear udder quarters was found
      to have significantly higher lactose content and significantly lower fat content
      than milk of the front udder quarters. The same trend found for fat content was
      observed for protein content, whereas no differences between the udder quarters
      were observed for urea content, SCS, or hyperkeratosis. Heritabilities for each
      udder quarter were in the following ranges: fat content 0.09+/-0.06 to 0.14+/
      0.06, protein content 0.20+/-0.09 to 0.33+/-0.07, lactose content 0.04+/-0.03 to
      0.16+/-0.07, urea content 0.13+/-0.07 to 0.22+/-0.08, SCS 0.18+/-0.06 to 0.32+/
      0.07, and hyperkeratosis 0.12+/-0.04 to 0.26+/-0.05. In our study,
      hyperkeratosis, protein content, and SCS showed higher heritabilities in the
      front udder quarters, fat content had higher heritabilities in the rear udder
      quarters, and no systematic pattern in heritability was observed for lactose
      content or urea content. Additive genetic correlations between all udder quarters
      were >0.90 for protein and urea contents, whereas they were remarkably low
      (<0.60) for SCS. For fat and lactose contents, the genetic correlations between
      the 2 front or between the 2 rear quarters, respectively, were notably higher
      than correlations between 1 front and 1 rear quarter, suggesting that the front
      and the rear udders could be considered as partly genetically different organs.
      The variability within the udder as such was found to be of low heritability
      (<0.10) in general, but repeatability was moderate to high for some traits
      (lactose content: 0.33+/-0.05, protein content: 0.53+/-0.05). Some of these
      findings can be explained by differences in the physiological background of the
      traits. 

PMID- 23871377
TI  - Estimation of genetic parameters for novel functional traits in Brown Swiss
      cattle.
AB  - The aim of this study was to estimate genetic parameters and accuracies of
      breeding values for a set of functional, behavior, and conformation traits in
      Brown Swiss cattle. These traits were milking speed, udder depth, position of
      labia, rank order in herd, general temperament, aggressiveness, milking
      temperament, and days to first heat. Data of 1,799 phenotyped Brown Swiss cows
      from 40 Swiss dairy herds were analyzed taking the complete pedigree into
      account. Estimated heritabilities were within the ranges reported in literature,
      with results at the high end of the reported values for some traits (e.g.,
      milking speed: 0.42+/-0.06, udder depth: 0.42+/-0.06), whereas other traits were
      of low heritability and heritability estimates were of low accuracy (e.g.,
      milking temperament: 0.04+/-0.04, days to first heat: 0.02+/-0.04). For most
      behavior traits, we found relatively high heritabilities (general temperament:
      0.38+/-0.07, aggressiveness: 0.12+/-0.08, and rank order in herd: 0.16+/-0.06).
      Position of labia, arguably an indicator trait for pathological urovagina, was
      genetically analyzed in this study for the first time, and a moderate
      heritability (0.28+/-0.06) was estimated. 

PMID- 23871378
TI  - Calving body condition score affects indicators of health in grazing dairy cows.
AB  - The objectives of this study were to determine the effect of calving body
      condition score (BCS) on cow health during the transition period in a pasture
      based dairying system. Feed inputs were managed during the second half of the
      previous lactation so that BCS differed at drying off (BCS 5.0, 4.0, and 3.0 for
      high, medium, and low treatments, respectively: a 10-point scale); feed allowance
      was managed after cows were dried off, such that the BCS differences established
      during lactation remained at the subsequent calving (BCS 5.5, 4.5, and 3.5; n=20,
      18, and 19, for high, medium, and low treatments, respectively). After calving,
      cows were allocated pasture and pasture silage to ensure grazing residuals >1,600
      kg of DM/ha. Milk production was measured weekly; blood was sampled regularly pre
      and postpartum to measure indicators of health, and udder and uterine health
      were evaluated during the 6 wk after calving. Milk weight, fat, protein, and
      lactose yields, and fat content increased with calving BCS during the first 6 wk
      of lactation. The effect of calving BCS on the metabolic profile was nonlinear.
      Before calving, cows in the low group had lower mean plasma beta-hydroxybutyrate
      and serum Mg concentrations and greater mean serum urea than cows in the medium
      and high BCS groups, which did not differ from each other. During the 6 wk after
      calving, cows in the low group had lower serum albumin and fructosamine
      concentrations than cows in the other 2 treatment groups, whereas cows in the low
      and medium-BCS groups had proportionately more polymorphonucleated cells in
      their uterine secretions at 3 and 5 wk postpartum than high-BCS cows. In
      comparison, plasma beta-hydroxybutyrate and nonesterified fatty acid
      concentrations increased linearly in early lactation with calving BCS, consistent
      with a greater negative energy balance in these cows. Many of the parameters
      measured did not vary with BCS. The results highlight that calving BCS and,
      therefore, BCS through early lactation are not effective indicators of functional
      welfare, with the analyses presented indicating that both low and high BCS at
      calving will increase the risk of disease: cows in the low group were more prone
      to reproductive compromise and fatter cows had an increased risk of metabolic
      diseases. These results are important in defining the welfare consequences of cow
      BCS.

PMID- 23871379
TI  - Determining the gelation temperature of beta-lactoglobulin using in situ
      microscopic imaging.
AB  - Evolution of microstructure during heat-induced gelation of beta-lactoglobulin
      (beta-LG) was investigated in situ using confocal laser scanning microscopy at
      various gel-preparation conditions: pH=2, 5, and 7; protein content=5, 10, and
      15%; and salt (NaCl) content=0, 0.1, and 0.3 M. The number and area of evolving
      beta-LG clusters were observed as a function of time and temperature and the data
      were fitted to a log-normal model and sigmoid model, respectively. The gelation
      temperature (Tgel) of the beta-LG system was determined from both the number
      (Tgel/N) and total area (Tgel/A) of beta-LG clusters versus temperature data. The
      range of Tgel/N and Tgel/A values for all the cases was 68 to 87 degrees C. The
      effect of pH was the most dominant on Tgel/N and Tgel/A, whereas the effects of
      beta-LG and salt contents were also statistically significant. Therefore, the
      combined effect of protein concentration, pH, and salt content is critical to
      determine the overall gel microstructure and Tgel. The Tgel/N and Tgel/A
      generally agreed well with Tgel determined by dynamic rheometry (Tgel/R). The
      correlations between Tgel/N and Tgel/A versus Tgel/R were 0.85 and 0.72,
      respectively. In addition, Tgel/N and Tgel/A values compared well with Tgel/R
      values reported in the literature. Based on these results, Tgel/N determined via
      in situ microscopy appears to be a fairly good representative of the
      traditionally measured gelation temperature, Tgel/R. 

PMID- 23871380
TI  - Properties of an alphas-casein-rich casein fraction: influence of dialysis on
      surface properties, miscibility, and micelle formation.
AB  - In this study, the surface tension, miscibility, and particle size distribution
      of a solution containing an alphas-casein (CN)-rich CN fraction (54 wt % alphas
      CN, 32 wt % beta-CN, and 15 wt % kappa-CN) were determined at pH 6.6. The
      nondialyzed CN fraction was compared with a dialyzed one. In the nondialyzed
      sample, every charge on the protein was compensated by 0.3 charges coming from
      counterions, whereas in the dialyzed sample, only 0.2 charges could be assigned
      to each charge on the protein. This relation was determined by calculating the
      charges at the proteins, taking the measured mineral content into account. The
      surface tension was measured as a function of the protein concentration by the du
      Nouy ring method at room temperature. Results indicated alterations in the
      surface properties after reduction of counterions. The equilibrium surface
      tension above the critical micelle concentration increased from 40.1*10(-3) to
      45*10(-3) N/m, the critical micelle concentration increased from 0.9*10(-4) to
      2*10(-3) mol/L, and the minimal area occupied per molecule at the surface
      increased from 2.4*10(-18) to 4.6*10(-18) m(2). Cloud points were determined by
      measuring the absorbance of CN solutions as a function of the temperature. The
      cloud points were found to be concentration dependent and had a minimum at 0.2 wt
      % at 34 degrees C for nondialyzed CN and at 0.25 wt % at 28 degrees C for
      dialyzed CN, again demonstrating the influence of counterion reduction. Below the
      cloud point, a micellar phase was found to exist. The hydrodynamic diameter of
      the micelles were characterized by dynamic light scattering in both auto- and
      cross-correlation mode. However, no influence of reduction in counterions could
      be observed, possibly due to the fact that dynamic light scattering is not a
      suitable method for this type of system. The presence of self-assembled
      structures was verified by freeze-fracture electron microscopy. The observed
      differences between dialyzed and nondialyzed samples were explained by changes in
      the counterion cloud surrounding the proteins. Consequently, the electrostatic
      interactions between as well as within the CN are altered by dialysis, which, in
      turn, affects the behavior at the surface as well as the properties in the
      solution. 

PMID- 23871381
TI  - Antioxidant enzymes in women with endometrial polyps: relation with sex hormones.
AB  - OBJECTIVE: To investigate whether antioxidant enzyme activities (superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione reductase) and lipid
      hydroperoxide levels in patients with endometrial polyps are influenced by the
      changes in sex hormones (estradiol, progesterone, FSH, and LH) during the
      menstrual cycle and in postmenopause. STUDY DESIGN: The material consisted of
      blood and endometrial tissue specimens from women diagnosed with endometrial
      polyps. Patients were divided into groups depending on the phase of the menstrual
      cycle--follicular or luteal--and the postmenopause. The activities of antioxidant
      enzymes and the lipid hydroperoxide levels were compared among the phases and a
      linear regression model was used to evaluate the associations between hormones
      and antioxidant/oxidant variables. RESULTS: In the blood of examined women, a
      significant difference in superoxide dismutase activity and lipid hydroperoxide
      levels was recorded among the phases. There was also a positive correlation
      between the estradiol concentration and superoxide dismutase. In polyp tissue, we
      recorded a phase-related difference in superoxide dismutase and glutathione
      peroxidase activities as well as in the lipid hydroperoxide levels. A negative
      correlation was observed between FSH/LH and glutathione peroxidase, and between
      LH and superoxide dismutase. CONCLUSION: Antioxidant enzymes and lipid
      hydroperoxide levels in patients with endometrial polyps are influenced by the
      changes in sex hormones during the menstrual cycle and after the menopause,
      pointing to a role of the observed relationship in polyp etiology.

PMID- 23871382
TI  - Effects of different doses of ethanol on sperm parameters, chromatin structure
      and apoptosis in adult mice.
AB  - OBJECTIVE: Chronic ethanol abuse causes reproductive organ failure and
      infertility in both humans and laboratory animals. Since sperm has a critical
      role in reproductive function, the objective of this unique study was to evaluate
      the effects of different doses of ethanol on sperm parameters, chromatin
      structure and apoptosis in adult mice. STUDY DESIGN: A total of 36 adult male
      mice were equally divided into four groups. Group 1 received ethanol (10%, v/v)
      containing saccharin (0.2%, w/v), group 2 received ethanol (5%, v/v) containing
      saccharin (0.1%, w/v), group 3 was treated with saccharin (0.2%, w/v) and group 4
      served as control and fed on basal diet for 35 days. Finally, the left cauda
      epididymis of each animal was cut and placed in Ham's F10 medium. Retrieved
      spermatozoa were used to analyze count, motility, morphology and viability. Sperm
      chromatin condensation and DNA integrity were assessed by five different tests
      including chromomycin A3 (CMA3), toluidine blue (TB), sodium dodecyl sulfate
      (SDS), and SCD (sperm chromatin dispersion) and sperm apoptosis was assessed by
      TUNEL. RESULTS: Following ethanol consumption, the sperm count diminished in the
      ethanol-treated groups. A decrease in sperm motility and an increase in the rate
      of morphological abnormalities (coiled and broken tails) were seen in the
      experimental and saccharin groups in comparison with controls. We showed that
      ethanol consumption can disturb sperm DNA integrity and chromatin remodeling and
      it may also induce sperm apoptosis. The rates of sperm apoptosis were 51.57 +/-
      7.45 and 42.85 +/- 6.76 in the high ethanol dose and low ethanol dose groups,
      respectively. CONCLUSION: The results showed that alcohol has negative effects on
      sperm parameters, chromatin/DNA integrity and apoptosis in mice. These alcohol
      induced sperm anomalies may be dose-dependent.

PMID- 23871383
TI  - Comparative characterization of STRO-1(neg)/CD146(pos) and STRO-1(pos)/CD146(pos)
      apical papilla stem cells enriched with flow cytometry.
AB  - OBJECTIVE: Stem Cells residing in the Apical Papilla (SCAP) of human permanent
      teeth represent a promising cell source for dental tissue regeneration.
      Therefore, the functional and molecular properties of specific subpopulations
      existing within heterogeneous cultures should be further investigated to give
      insight whether their selection could be beneficial for targeted therapeutic
      applications. DESIGN: In this study we extensively characterized SCAP cultures
      established from 10 healthy subjects, as well as their STRO-1(pos/)CD146(pos) and
      STRO-1(neg/)CD146(pos) subpopulations isolated with fluorescence-activated cell
      sorting. SCAP were analyzed for embryonic (Nanog, Oct3/4, SSEA-3, TRA-1-60),
      mesenchymal (STRO-1, CD146/MUC18, CD105/endoglin, CD24, CD90/Thy-1, CD81-TAPA,
      CD34, CD49f/a6-integrin), neural (CD271/NGFR, nestin) and hematopoietic (CD117/c
      kit, CD45) stem cell (SC) markers using flow cytometry. Multipotentiality was
      evaluated with culture specific staining (Alizarin-Red-S, Oil- Red-O) and RT-PCR
      analysis for osteo/odontogenic (DSPP, BSP, ALP, osteocalcin, osteonectin, BMP-2,
      Runx2), adipogenic (lipoprotein-lipase-LPL) and neurogenic (Neurofilament/NFL-L,
      nestin, beta-tubulin-III, NCAM) markers. RESULTS: Our results showed that the
      STRO-1(pos)/CD146(pos) subpopulation demonstrated higher CFU efficiency and much
      higher expression of several embryonic and mesenchymal SC markers compared to the
      non-sorted SCAP. They also showed enhanced odontogenic differentiation potential,
      as evidenced by higher mineralization capacity and expression of
      osteo/odontogenic markers. By contrast, absence of STRO-1 in the STRO
      1(neg)/CD146(pos) subpopulation yielded the opposite results and was associated
      with significant downgrading of the above-mentioned properties. CONCLUSIONS:
      These results suggest that STRO-1(pos)/CD146(pos) SCAP cells represent a very
      promising adult MSCs source with enhanced multipotent SC properties that could be
      easily isolated with simple flow cytometric methods to be used for tissue
      engineering applications.

PMID- 23871384
TI  - Morphological and biomechanical features of the temporomandibular joint disc: an
      overview of recent findings.
AB  - The temporomandibular joint is a type of synovial joint with unique structure and
      function. Between the mandibular condyle and the mandibular fossa there is a
      dense fibrocartilaginous oval articular disc, temporomandibular joint disc. This
      disc serves as a nonossified bone, thus permitting the complex movements of the
      joint, and plays a major role in jaw function by providing stress distribution
      and lubrication in the temporomandibular joint. Pathological mechanical loads are
      one of the principal causes of temporomandibular joint disc displacement. There
      is a high frequency of temporomandibular joint disc disorders and treatment
      options are very limited. For this reason, it is necessary to examine possible
      alternatives to current treatment options like physiotherapy, drugs, splints or
      surgical techniques. Recent discoveries in the field of structure and functions
      of temporomandibular joint disc have created the need for their particular
      systematization, all in order to create an implant that would be used to replace
      the damaged disc and be more similar to the natural one. There is a need to more
      fully meet the morphology and biomechanical properties of the temporomandibular
      joint disc, and using tissue engineering, make a substitute for it, as faithful
      as possible, in a case where the natural TMJ disc is damaged so much that the
      normal function of the joint can be preserved only through implanted disc.
      Therefore, the aim of this paper was to describe morphology and structure, as
      well as biomechanical properties of the TMJ disc, in light of the possible
      applications of this knowledge for the purposes of tissue engineering. 

PMID- 23871385
TI  - Eumycetoma of the foot caused by Exophiala jeanselmei in a Guinean woman.
AB  - Eumycetomas are chronic infectious entities characterized by presence of mycotic
      grains in (sub-)cutaneous tissues, after accidental inoculation of an exogenous
      filamentous fungus in the skin. The lesions evolve towards painless pseudotumor
      of the soft parts. We report the original case of a Guinean woman exhibiting
      eumycetoma of the right foot. Both laboratory tests identified a dematiaceous
      fungus, Exophiala jeanselmei, as the responsible infectious agent. A medical
      treatment with voriconazole alone was sufficient to notice a substantial clinical
      improvement. This finding is unusual as E. jeanselmei is uncommon in Guinea
      Conakry, and as optimal treatment rather associate antifungal azoles and surgical
      excision. 

PMID- 23871386
TI  - Effectiveness of low-profile supplemental fixation in anterior cruciate ligament
      reconstructions with decreased bone mineral density.
AB  - PURPOSE: The purpose of this study was to compare anterior cruciate ligament
      (ACL) fixation using a bioabsorbable interference screw (BIS) and a supplemental
      low-profile suture anchor (PushLock 4.5-mm polyetheretherketone anchor; Arthrex,
      Naples, FL) with a standard BIS fixation to determine if fixation methods were
      dependent on tibial bone mineral density (BMD). METHODS: Ten matched pairs of
      fresh-frozen human female knee specimens (20 total) were harvested with specimen
      ages ranging from 40 to 65 years. The BMD for each specimen was determined with a
      dual-energy x-ray absorptiometry scanner. The specimens were divided into 2
      groups, 1 with a BIS and the other with a BIS plus a PushLock. Tibial-sided ACL
      fixation with hamstring tendon grafts was performed on all the specimens. Then,
      load to failure and stiffness were biomechanically tested. RESULTS: The BIS-plus
      PushLock specimens had a significantly higher mean yield load compared with
      specimens with the BIS alone (702 N v 517 N, P = .047). However, in samples with
      lower bone density, there was no statistically significant difference in failure
      loads between fixation techniques (P = .8566 at BMD of 0.5 g/cm(2)). As the bone
      density of the samples increased, the failure loads increased for both techniques
      (P < .0001 for PushLock and P = .0057 for BIS). This BMD-associated increase was
      greater for the PushLock (P = .0148), resulting in a statistically significant
      difference in failure load at the upper range tested (P = .0293 at BMD of 0.9
      g/cm(2)). CONCLUSIONS: Supplemental fixation of ACL reconstructions with a
      PushLock is beneficial in persons with a normal BMD of the proximal tibia, but at
      a lower BMD, there was no difference in our study. CLINICAL RELEVANCE:
      Individuals with normal BMDs may benefit from this supplemental fixation.
      However, caution should be used in postmenopausal women or individuals with
      chronic ACL injuries when using this fixation strategy.

PMID- 23871387
TI  - Lumbar facet cyst resolution following anterior interbody fusion.
AB  - Facet cysts are a relatively common source of neural compression in the lumbar
      spine. Open decompression and fusion are frequently used to treat the stenosis
      and instability associated with this pathology. Recently, anterior lumbar
      interbody fusion (ALIF) has increased in popularity for the treatment of lumbar
      degenerative conditions. ALIF may achieve indirect decompression of the neural
      elements with less surgical morbidity than conventional open approaches. To date,
      there are no published reports describing the use of indirect decompression or
      interbody fusion for the treatment of facet cysts. We report a patient who
      developed an L4-L5 facet cyst secondary to degenerative changes and
      spondylolisthesis. ALIF with posterior instrumentation was used to address his
      condition. Six months after surgery, the patient had complete resolution of his
      symptoms. MRI revealed complete resolution of the facet cyst. This patient
      provides previously unreported evidence that interbody fusion alone may result in
      facet cyst resolution. Clinical studies are needed to evaluate if interbody
      fusion can consistently relieve the symptoms associated with facet cysts without
      the use of direct decompression. 

PMID- 23871388
TI  - Increased antioxidant response and capability to produce ROS in hemocytes of
      Pinna nobilis L. exposed to anthropogenic activity.
AB  - Environmental pollutants exert immunotoxical effects on aquatic organisms. The
      aim was to determine the antioxidant response, markers of oxidative damage and
      reactive oxygen species production in hemocytes of Pinna nobilis, the largest
      endemic bivalve in the Mediterranean Sea, under anthropogenic pressure. P.
      nobilis individuals were collected from two locations along Mallorca Island
      waters attending to different degree of human impact and the hemocytes were
      obtained. Specimens from the impacted area showed increased activities of the
      antioxidant enzymes - catalase, superoxide dismutase, glutathione peroxidase and
      glutathione reductase -, myeloperoxidase activity and reduced glutathione levels.
      No differences in oxidative damage markers - malondiahdehyde and carbonyl index -
      were evidenced between the pristine and polluted areas. Hemocytes from the
      polluted area presented increased capability to generate reactive oxygen species
      and nitrite/nitrate when activated. In conclusion, the human activities primed
      hemocytes for oxidative burst and increased the antioxidant mechanism without
      evidence of oxidative damage.

PMID- 23871389
TI  - Life-time and current suicide-ideation in Australian secondary school students:
      Socio-demographic, health and psychological predictors.
AB  - BACKGROUND: This study involved a multi-level analysis of factors related to self
      reported suicidality (both current and life-time) in adolescents METHODS: A
      sample of 2552 students aged 14-16 years answered questions relating to
      demographics, social and familial functioning, psychological well-being and
      suicidality. RESULTS: Suicidality, defined as being at least some element of
      reported suicide ideation, Behaviourally, suicidality was also more likely if
      students smoked, drank alcohol without adult supervision or if they took illicit
      drugs was more likely in girls, and in those with poorer social, family and
      psychological functioning. Behaviourally, suicidality was also more likely if
      students smoked, drank alcohol or took illicit drugs. Multi-level modelling
      showed that negative affect, substance use and the presence of romantic
      relationships were most strongly associated with suicidality. Both current and
      life-time measures of suicidality showed similar results. Both models suggested
      that the presence of substance use in teenagers is a potentially useful indicator
      of elevated suicide risk and that many of the social problems commonly associated
      with suicidality are likely to be mediated by negative affective states.
      LIMITATIONS: The study had several limitations. First, it was cross-sectional so
      it was not possible to examine how variables measured at one time predicted
      subsequent suicidality. Second, the present analyses were based on a single
      measure of suicidality that did not differentiate between ideation and attempts.
      Thus, the analyses did not indicate the severity of the suicidality: whether it
      involved ideation or actual attempts. CONCLUSIONS: Adolescent girls and
      adolescents with poor social and family functioning and those who engage in
      substance use are at risk of suicidal ideation (a known precursor of suicide
      attempts). School counsellors and teachers need to be aware of the risks.

PMID- 23871390
TI  - VEGF plasma level variations in duloxetine-treated patients with major
      depression.
AB  - BACKGROUND: The vascular endothelial growth factor (VEGF) signaling, which
      modulates angiogenesis and neurogenesis within the neurovascular unit, might play
      an important role in the neuro-endocrine-immune (NEI) stress-adaptation system.
      Recent evidence suggests that VEGF is involved in the pathophysiology of a number
      of diseases including major depressive disorder (MDD) and is affected by some
      treatments, including antidepressants. The objective of the study was to
      investigate the VEGF level variations in MDD patients during antidepressant
      treatment with duloxetine, a relatively new SNRI. METHODS: A total of 30 MDD
      patients and 32 healthy controls were assessed using the Hamilton Depression
      Scale (HAM-D) and monitored for VEGF plasma levels at baseline, week 6 and week
      12 of duloxetine treatment (60 mg/day) and at baseline, respectively. RESULTS:
      According to early clinical response to duloxetine (defined at week 6 by
      reduction>50% of baseline HAM-D score), the MDD patients were divided into early
      responders (ER) and early non-responders (ENR). During duloxetine treatment, we
      found an opposite trend in the VEGF levels between ER and ENR: in ER the VEGF
      levels significantly increased in association with clinical response at W6, while
      in ENR the VEGF levels significantly decreased in association with an overall
      clinical response at W12. LIMITATIONS: Small sample size. CONCLUSIONS: The
      opposite trends in VEGF levels, increasing in ER and decreasing in ENR, might
      reflect differential Norepinephrine/Serotonin effects of duloxetine on
      differential neurobiological backgrounds of depressive syndromes. Overall, the
      modulation of VEGF signaling within the neurovascular unit during antidepressant
      treatment could hypothetically favor the remodeling of neural circuitry,
      contributing to adaptive adjustment of the NEI stress-adaptation system.

PMID- 23871391
TI  - Toxicity of indoxyl derivative accumulation in bacteria and its use as a new
      counterselection principle.
AB  - In this work we describe the conditional toxic effect of the expression of
      enzymes that cleave 5-bromo-4-chloro-3-indolyl (BCI) substrates and its use as a
      new counterselection principle useful for the generation of clean and unmarked
      mutations in the genomes of bacteria. The application of this principle was
      demonstrated in the thermophile Thermus thermophilus HB27 and in a mesophile for
      which currently no counterselection markers are available, Micrococcus luteus
      ATCC 27141. For T. thermophilus, the indigogenic substrate BCI-beta-glucoside was
      used in combination with the T. thermophilus beta-glucosidase gene (bgl). For M.
      luteus, a combination of BCI-beta-galactoside and the E. coli lacZ gene was
      implemented. We observed a strong growth-inhibiting effect when the strains were
      grown on agar plates containing the appropriate BCI substrates, the inhibition
      being proportional to the substrate concentration and the level of bgl/lacZ
      expression. The growth inhibition apparently depends on intracellular BCI
      substrate cleavage and accumulation of toxic indoxyl precipitates. The bgl and
      lacZ genes were used as counterselection markers for the rapid generation of scar
      less chromosomal deletions in T. thermophilus HB27 (both in a Deltabgl and in a
      wild type background) and in M. luteus ATCC 27141. In addition to Thermus and
      Micrococcus, sensitivity to BCI substrate cleavage was observed for other Gram
      negative and Gram-positive species belonging to various bacterial phyla,
      including representatives of the genera Staphylococcus, Bacillus,
      Corynebacterium, Rhodococcus, Paracoccus and Xanthomonas. Thus, the toxicity of
      indoxyl derivative accumulation upon BCI substrate cleavage can be used for
      selection purposes in a broad range of microorganisms. 

PMID- 23871392
TI  - [Granulosa cell tumor: difficulty of diagnosis and contribution of imaging].
AB  - Granulosa tumors (GT) are rare neoplasms, difficult to diagnose in a preoperative
      stage. We report a set of seven patients affected by GT admitted in Amiens
      University Hospital, collated with a review of the literature (n=379). Our aim
      was to report the clinical and radiological characteristics of GT, in order to
      improve preoperative diagnosis. The average age of the subjects was 50.8 years
      old among the bibliographical search, and 37years old for the observations
      reported in Amiens. The principal circumstances of diagnosis were vaginal
      bleeding, abdominal pain and infertility. Ultrasound was the most frequently
      investigation, revealing GT as a large unilateral solid and cystic mass. The
      computed tomodensitometry (CT) allowed to precise the locoregional extension.
      Magnetic Resonance Imaging (MRI) appeared to be interesting to clarify lesions,
      showing GT as a solid mass with a cystic component or as a multicystic mass.
      Hormonal assays (inhibin B and/or anti-Mullerian hormone) can provide valuable
      assistance in diagnosis, despite their cost and lack of availability. In view of
      the clinical and radiological presentation of the reported and literature review
      cases, we suggest hormonal assays among perimenopausal women presenting with an
      unusual radiological aspect of an annexial mass. 

PMID- 23871393
TI  - The experience of acute leukaemia in adult patients: a qualitative thematic
      synthesis.
AB  - PURPOSE: The aim of this review was to systematically identify and synthesise all
      qualitative evidence on how adult patients diagnosed with acute leukaemia
      experience living with their illness. METHODS: A systematic search strategy was
      developed comprising of two search strings: i) acute leukaemia and ii)
      qualitative methodology. The search strategy was run in seven electronic
      databases (Medline, CINAHL, PsychINFO, EMBASE, BNI & Archive, SSCI and ASSIA).
      Nine qualitative studies in adult patients with acute leukaemia, published in
      peer reviewed journals between 01/1990 and 01/2013 were included in the final
      sample. RESULTS: The qualitative thematic synthesis resulted in the development
      of a conceptual model describing a person's path to build a renewed self.
      Following the initial blow of diagnosis with the range of initial reactions,
      patients with acute leukaemia are living in a contracting world; they have to
      deal with the life in hospital, the several losses and the impact of their
      illness on their emotions and interpersonal relationships. Several factors take
      up a buffering role at that stage: coping, support, information and hope.
      Finally, patients accommodate acute leukaemia in their lives through re
      evaluating personal values and assigning new meaning to their experience.
      CONCLUSIONS: Results from this thematic synthesis are indicative of the impact of
      acute leukaemia on patients' lives and the processes they use to make sense and
      accommodate the illness in their life. Increasing our understanding of these
      processes is warranted to improve patient care.

PMID- 23871394
TI  - Epidemiological characteristics of fatal traffic accidents in Fars province,
      Iran: a community-based survey.
AB  - OBJECTIVES: To determine the epidemiological characteristics of fatal traffic
      accidents in Fars province, Iran. STUDY DESIGN: This cross-sectional study
      included 3642 traffic accident deaths in Fars province, Iran between November
      2009 and November 2011. The data source was the Fars Forensic Medicine Registry,
      which covers the entire province. According to Iranian law, all deaths resulting
      from injuries or accidents must be investigated to determine the exact cause of
      death by autopsy. All such deaths are referred to forensic medicine centres in
      each city, and all data are sent to the main centre in Shiraz, the capital city
      of Fars province. RESULTS: Males accounted for 78.3% of the decedents (sex ratio
      of almost 3.6:1), and the mean +/- standard deviation age of all decedents was
      32.2 +/- 20.3 years. Autopsy reports indicated that head trauma was the most
      common cause of death. Most collisions were vehicle-vehicle crashes (52.3%), with
      cars and motorcycles being the most prevalent modes of transport (39.6% and
      24.6%, respectively). Fatal accidents were most common during the summer. Most
      fatal injuries (61.4%) occurred on outer-city roads and 27.4% occurred on inner
      city roads. Significant associations were found between decedent's status (car
      driver, motorcycle driver or passenger, pedestrian or passenger) and interval
      between injury and death, light conditions at the scene of the accident, place of
      death, site of injury and cause of death. CONCLUSION: Although the clinical
      management of trauma patients has improved in Iran, coordination between trauma
      system organizations is required to decrease the burden of injuries.

PMID- 23871395
TI  - A framework to evaluate the development and implementation of a comprehensive
      public health strategy.

PMID- 23871396
TI  - A case of CRB1-negative Coats-like retinitis pigmentosa.
AB  - Retinitis pigmentosa is a heterogeneous group of ocular diseases that causes
      progressive degeneration of the photoreceptor cells mainly affecting the rods of
      the peripheral retina. The association between retinitis pigmentosa and exudative
      retinopathy was first described in 1956 and has been called "Coats-like retinitis
      pigmentosa." Mutations in the Crumbs homolog 1 (CRB1) gene have been reported as
      a risk factor for developing Coats-like changes in patients with autosomal
      recessive retinitis pigmentosa. We report the case of a 15-year-old girl affected
      by CRB1 gene-negative retinitis pigmentosa and Coats-like exudative vasculopathy
      who was successfully treated with laser photocoagulation. 

PMID- 23871397
TI  - Use of hormonal contraceptives and HIV acquisition in women: a systematic review
      of the epidemiological evidence.
AB  - Whether or not the use of hormonal contraception affects risk of HIV acquisition
      is an important question for public health. We did a systematic review, searching
      PubMed and Embase, aiming to explore the possibility of an association between
      various forms of hormonal contraception and risk of HIV acquisition. We
      identified 20 relevant prospective studies, eight of which met our minimum
      quality criteria. Of these eight, all reported findings for progestin-only
      injectables, and seven also reported findings for oral contraceptive pills. Most
      of the studies that assessed the use of oral contraceptive pills showed no
      significant association with HIV acquisition. None of the three studies that
      assessed the use of injectable norethisterone enanthate showed a significant
      association with HIV acquisition. Studies that assessed the use of depot
      medroxyprogesterone acetate (DMPA) or non-specified injectable contraceptives had
      heterogeneous methods and mixed results, with some investigators noting a 1.5-2.2
      times increased risk of HIV acquisition, and others reporting no association.
      Thus, some, but not all, observational data raise concern about a potential
      association between use of DMPA and risk of HIV acquisition. More definitive
      evidence for the existence and size of any potential effect could inform
      appropriate counselling and policy responses in countries with varied profiles of
      HIV risk, maternal mortality, and access to contraceptive services. 

PMID- 23871398
TI  - Effects of aerobic interval training on metabolic complications and
      cardiorespiratory fitness in young adults with psychotic disorders: a pilot
      study.
AB  - AIM: To assess the feasibility of implementing a 14-week aerobic interval
      training (AIT) program within a first-episode psychosis (FEP) service and its
      efficacy in improving metabolic outcomes and cardiorespiratory fitness. METHOD:
      Twenty-five male subjects participated in 30-minute sessions of AIT twice a week.
      RESULTS: Sixteen of 25 subjects completed the training program. There was a
      significant decrease in waist circumference (WC; -4.3 cm; p=0.015), resting heart
      rate (-8.6 bpm; p<0.05) and a 38% increase in VO2max (p<0.001). The decrease in
      WC (-5.6 cm; p<0.01) was more pronounced for subjects who completed at least 64%
      of the planned sessions. CONCLUSION: An AIT program could be implemented in FEP
      patients and improve WC and cardiorespiratory fitness over a relatively short
      period.

PMID- 23871399
TI  - Comparison of fracture risk between patients with ileal pouch-anal anastomosis
      for ulcerative colitis and the general population.
AB  - BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA)
      is the preferred surgical treatment for ulcerative colitis (UC). Little is known
      of how the operation affects bone metabolism and fracture risk. The aim of this
      retrospective cohort study was to investigate fracture risk and serum markers of
      bone metabolism following IPAA in a national cohort of Danish UC patients.
      METHODS: Diagnostic codes for 1757 patients and 8785 controls were obtained from
      the National Patient Register while blood results were collected from a regional
      database. Postoperative fracture free survival was evaluated on a Kaplan-Meier
      plot. Fracture hazard ratios (HR) after IPAA were calculated from Cox
      proportional hazards regression analysis. RESULTS: Fracture risk after IPAA was
      significantly reduced (adjusted HR = 0.49, 95% CI: 0.43; 0.55, p<0.001). Prior
      fractures and alcoholism independently increased fracture risk significantly.
      Osteoporotic fracture risk after IPAA was reduced, significantly for wrist
      fractures (aHR = 0.39, 95% CI: 0.22; 0.71, p = 0.002), and borderline
      insignificantly for spine fractures (aHR = 0.51, 95% CI: 0.26; 1.01, p = 0.054).
      Vitamin D and calcium levels were significantly higher in the patient group (61.2
      nmol/L vs. 58.9 nmol/L, p = 0.04 and 1.24 mmol/L vs. 1.21 mmol/L, p<0.01,
      respectively), while parathyroid hormone and phosphate levels were significantly
      lower (4.9 pmol/L vs. 6.2 pmol/L, p<0.01 and 1.08 mmol/L vs. 1.12 mmol/L, p<0.01,
      respectively). CONCLUSION: Fracture risk after IPAA is significantly reduced
      compared to the general population. Prospective studies are needed to verify the
      biochemical results.

PMID- 23871400
TI  - Reply to Dr. Pavlidis et al's letter.

PMID- 23871401
TI  - Electrocardiographic predictors of sudden cardiac death from a large Finnish
      general population cohort.

PMID- 23871403
TI  - Making individualized decisions in the midst of uncertainties: the case of
      prostate cancer and biochemical recurrence.

PMID- 23871402
TI  - Impact of histologic subtype on cancer-specific survival in patients with renal
      cell carcinoma and tumor thrombus.
AB  - BACKGROUND: Although different prognostic factors for patients with renal cell
      carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the
      prognostic value of histologic subtype in these patients remains unclear.
      OBJECTIVE: We analyzed the impact of histologic subtype on cancer-specific
      survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively analyzed
      the records of 1774 patients with RCC and TT who underwent radical nephrectomy
      and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable ordered logistic and Cox
      regression models were used to quantify the impact of tumor histology on CSS.
      RESULTS AND LIMITATIONS: Overall 5-yr CSS was 53.4% (confidence interval [CI],
      50.5-56.2) in the entire group. TT level (according to the Mayo classification of
      macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III
      in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell
      carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in
      8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated
      with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable
      analysis, the presence of pRCC was independently associated with CSS (hazard
      ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status,
      distant metastasis, and fat invasion were also independently associated with CSS.
      CONCLUSIONS: In our multi-institutional series, we found that patients with pRCC
      and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had
      significantly worse cancer-specific outcomes when compared with patients with
      other histologic subtypes of RCC. We confirmed that higher TT level and fat
      invasion were independently associated with reduced CSS.

PMID- 23871404
TI  - [Congenital ciliary dyskinesia. Focus].
AB  - Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease, caused by
      specific primary structural and/or functional abnormalities of the motile cilia.
      Prevalence, about 1/15,000 to 1/30,000, is probably underestimated, as diagnosis
      might not be evocated in absence of Kartagener syndrome. Diagnosis is confirmed
      in presence of abnormal ciliary motility as well as ciliary ultrastructure.
      Disease-causing mutations in at least 16 genes have already been identified;
      analysis will be guided by the type of ultrastructural abnormalities. An early
      and adequate diagnosis and therapy can theoretically improve the prognosis of the
      disease. 

PMID- 23871405
TI  - Containing a Lassa fever epidemic in a resource-limited setting: outbreak
      description and lessons learned from Abakaliki, Nigeria (January-March 2012).
AB  - OBJECTIVES: Despite the epidemic nature of Lassa fever (LF), details of outbreaks
      and response strategies have not been well documented in resource-poor settings.
      We describe the course of a LF outbreak in Ebonyi State, Nigeria, during January
      to March 2012. METHODS: We analyzed clinical, epidemiological, and laboratory
      data from surveillance records and hospital statistics during the outbreak.
      Fisher's exact tests were used to compare proportions and t-tests to compare
      differences in means. RESULTS: The outbreak response consisted of effective
      coordination, laboratory testing, active surveillance, community mobilization,
      contact and suspected case evaluation, and case management. Twenty LF cases (10
      confirmed and 10 suspected) were recorded during the outbreak. Nosocomial
      transmission to six health workers occurred through the index case. Only 1/110
      contacts had an asymptomatic infection. Overall, there was high case fatality
      rate among all cases (6/20; 30%). Patients who received ribavirin were less
      likely to die than those who did not (p=0.003). The mean delay to presentation
      for patients who died was 11 +/- 3.5 days, while for those who survived was 6 +/-
      2.6 days (p<0.001). CONCLUSIONS: The response strategies contained the epidemic.
      Challenges to control efforts included poor local laboratory capacity,
      inadequate/poor quality of protective materials, fear among health workers, and
      inadequate emergency preparedness.

PMID- 23871406
TI  - Mid-term results of total knee arthroplasty with a porous tantalum monoblock
      tibial component.
AB  - BACKGROUND: The objectives of the present study were to assess the mid-term
      results of cementless total knee arthroplasty (TKA) with the porous tantalum
      monoblock tibial component and to examine the time course of bone changes on
      plain radiographs. METHODS: The subjects were 32 patients, 29 patients were
      available for follow-up. We investigated the mid-term results of TKA after a mean
      follow-up period of 7 years and 8 months. We also examined changes of the bone
      over time on plain radiographs. RESULTS: The Knee Society Clinical Rating scores
      showed significant improvement. Bone changes around the tibial component were as
      follows: new bone formation and longitudinal trabecular thickening in 41.4% (Type
      A), only longitudinal trabecular thickening in 41.4% (Type B), and no changes in
      17.2% (Type C). Type A and B changes were more frequent in patients with
      osteoarthritis, whereas Type C was only seen in patients with rheumatoid
      arthritis. Three knees had an initial gap, but this disappeared in all cases, and
      no new radiolucent lines were detected. Stress shielding was observed in seven
      knees (21.9%), but there was no implant loosening related to it. When we examined
      the relationship between the mechanical axis and the locations of the tips of the
      tibial pegs in patients with or without stress shielding, no significant
      differences were found. CONCLUSIONS: The results of mid-term follow-up have
      demonstrated favorable bone ingrowth, suggesting that porous tantalum is a
      promising material for cementless TKA.

PMID- 23871408
TI  - KDOQI US commentary on the 2012 KDIGO clinical practice guideline for
      glomerulonephritis.
AB  - Glomerulonephritis (GN) is an important cause of morbidity and mortality in
      patients of all ages throughout the world. Because these disorders are relatively
      rare, it is difficult to perform randomized clinical trials to define optimal
      treatment for many of the specific glomerulopathies. In the absence of high-grade
      evidence to guide the care of glomerular diseases, in June 2012, KDIGO (Kidney
      Disease: Improving Global Outcomes) published an international clinical guideline
      for GN. The Work Group report represents an important review of the literature in
      this area and offers valid and useful guidelines for the most common situations
      that arise in the management of patients with glomerular disease. This
      commentary, developed by a panel of clinical experts convened by the National
      Kidney Foundation, attempts to put the GN guideline into the context of the US
      health care system. Overall, we support the vast majority of the recommendations
      and highlight select areas in which epidemiological factors and medical practice
      patterns in this country justify modifications and adjustments in order to
      achieve favorable outcomes. There remain large gaps in our knowledge of the best
      approaches to treat glomerular disease and we strongly endorse an expanded
      clinical research effort to improve the health and long-term outcomes of children
      and adults with GN. 

PMID- 23871407
TI  - Pregnancy-associated polyuria in familial renal glycosuria.
AB  - A pregnant woman presented at gestational week 28 with loss of consciousness and
      profound polyuria. Further characterization revealed osmotic diuresis due to
      massive glycosuria without hyperglycemia. Glycosuria reduced substantially
      postpartum, from approximately 100 to approximately 30 g/1.73 m2 per day. DNA
      sequencing analysis of the SLC5A2 gene encoding the renal glucose transporter
      SGLT2 showed a homozygous frame-shift mutation (occurring after the glutamine at
      amino acid 168 and leading to premature termination of the protein at amino acid
      186) diagnostic of familial renal glycosuria. Pregnant women with familial renal
      glycosuria can be at risk of profound polyuria during pregnancy due to the
      associated increase in glycosuria. These findings also have implications for the
      use of SGLT2 inhibitors in clinical practice.

PMID- 23871409
TI  - Increased attempts to suppress negative and positive emotions in Borderline
      Personality Disorder.
AB  - Patients with Borderline Personality Disorder (BPD) show evidence of disturbed
      emotion regulation. In particular, patients may try to suppress their emotions
      with possibly negative effects on mental health. We investigated the suppression
      of both negative and positive emotions in BPD patients and healthy participants.
      Thirty BPD patients and 30 matched healthy controls were assessed for emotion
      suppression using the Emotion Acceptance Questionnaire (EAQ). In addition, we
      administered additional questionnaires to validate emotion suppression findings.
      BPD patients reported increased attempts to suppress both negative and positive
      emotions. These findings indicate that BPD patients are not simply acting out
      negative emotions. Therapeutic approaches that focus on emotion acceptance of
      emotions are supported by our study data. Apart from negative emotions, treatment
      programs should consider positive emotions as well. 

PMID- 23871410
TI  - Asperger syndrome and "non-verbal learning problems" in a longitudinal
      perspective: neuropsychological and social adaptive outcome in early adult life.
AB  - Co-existence of Asperger syndrome (AS) and non-verbal learning disability (NLD)
      has been proposed based on the observation that people with AS tend to have
      significantly higher verbal than performance IQ (VIQ > PIQ by >= 15 points), one
      of the core features of NLD. In the present study we examined neuropsychological
      and social adaptive profiles with "non-verbal learning problems" associated with
      NLD in a group of individuals with AS followed from childhood into early adult
      life. The group was divided into three subgroups: (i) persistent NLD (P-NLD),
      i.e. NLD (VIQ > PIQ) both in childhood and early adulthood occasions, (ii)
      childhood NLD (CO-NLD), i.e. NLD (VIQ > PIQ) only at original diagnosis, or (iii)
      No NLD (VIQ > PIQ) ever (NO-NLD). All three subgroups were followed prospectively
      from childhood into adolescence and young adult life. One in four to one in five
      of the whole group of males with AS had P-NLD. The P-NLD subgroup had poorer
      neuropsychological outcome in early adult life than did those with CO-NLD and
      those with NO-NLD. There were no unequivocal markers in early childhood that
      predicted subgroup status in early adult life, but early motor delay and a
      history of early speech-language problems tended to be associated with P-NLD.

PMID- 23871411
TI  - Contrast-enhanced ultrasonography for assessment of activity of Crohn's disease:
      the future?

PMID- 23871412
TI  - Treatment of inflammatory bowel disease with methotrexate in clinical practice.

PMID- 23871413
TI  - Activity of antifungal combinations against Aspergillus species evaluated by
      isothermal microcalorimetry.
AB  - We evaluated the activity of antifungals alone or in combination against
      Aspergillus fumigatus and Aspergillus terreus by real-time measurement of fungal
      growth-related heat production. Amphotericin B, voriconazole, caspofungin, and
      anidulafungin were tested alone or in combination. Heat production was measured
      in Sabouraud dextrose broth containing 10(5)Aspergillus conidia/mL for 48 h at 37
      degrees C. Antifungal activity was evaluated by measuring the heat detection
      time relative to the growth control. Against A. fumigatus, the voriconazole
      echinocandin combination demonstrated longer heat detection time than each
      antifungal alone. Against A. terreus, the combination amphotericin B-echinocandin
      prolonged the heat detection time, compared to each antifungal alone. In
      contrast, the echinocandin-voriconazole combination did not increase the heat
      detection time, compared to voriconazole alone. None of the antifungal
      combinations decreased the heat detection time compared to the antifungals alone
      (e.g. antagonism was not observed). Microcalorimetry has the potential for real
      time evaluation of antifungal combinations against Aspergillus spp. 

PMID- 23871414
TI  - Diagnostic dilemma in a returning traveler with fever.
AB  - This case report of fever of unknown origin in a returning traveler from South
      America illustrates the need for a thorough understanding of limitations of
      laboratory testing modalities in order to prevent delays in diagnosis in
      potentially fatal but curable diseases. 

PMID- 23871415
TI  - Sirtuin-3 (SIRT3) expression is associated with overall survival in esophageal
      cancer.
AB  - Sirtuin-3 (SIRT3) was immunostained in 94 samples of esophageal cancer tissues
      and semiquantified using the HSCORE method to evaluate the predictive value of
      SIRT3 expression levels on esophageal cancer outcome. The relationship between
      SIRT3 expression and the 5-year survival rate of postoperational esophageal
      cancer patients was assessed with the Kaplan-Meier method. High expression of
      SIRT3 is associated with a shorter survival time in esophageal cancer patients,
      as shown by the log-rank test (P = .007), and the level of SIRT3 expression was
      identified as an independent predictor for esophageal cancer outcome using Cox
      proportional hazards model analysis (relative risk, 2.061; 95% confidence
      interval, 1.050-4.046; P = .036). SIRT3 expression was associated with esophageal
      cancer outcome. The analysis of SIRT3 levels can help in the identification of
      patient subgroups that are at high risk for poor disease outcomes.

PMID- 23871416
TI  - Environmental friendly cold-mechanical/sonic enzymatic assisted extraction of
      genipin from genipap (Genipa americana).
AB  - An efficient cold-mechanical/sonic-assisted extraction technique was developed
      for extraction of genipin from genipap (Genipa americana) peel. Ultrasound
      assisted extraction (285 W, 24 kHz) was performed at 5, 10 and 15  degrees C for
      5, 10 and 15 min. After cold-extraction, genipin was separated from pectin and
      proteins by aid of fungal pectinesterase. The maximum yield of non-cross-linked
      genipin was 7.85+/-0.33 mg/g, at 10  degrees C for 15 min by means of ultrasound
      extraction. The protein amount in extracts decreased in all samples. If
      mechanical process is combined with ultrasound assisted extraction the yield is
      increased by 8 times after the pectinesterase-assisted polyelectrolyte complex
      formation between pectic polysaccharides and proteins, avoiding the typical cross
      linking of genipin. This novel process is viable to obtain non-cross-linked
      genipin, to be used as a natural colorant and cross-linker in the food and
      biotechnological industries.

PMID- 23871418
TI  - Docetaxel: time to reassess combination strategies.

PMID- 23871419
TI  - Evaluation of anticancer effects and enhanced doxorubicin cytotoxicity of
      xanthine derivatives using canine hemangiosarcoma cell lines.
AB  - Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac,
      and central nervous system stimulatory effects. Moreover, caffeine inhibits the
      development of tumors induced by various carcinogens. The aim of this work was to
      elucidate the anticancer effects on apoptosis of xanthine derivatives alone and
      with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or
      without doxorubicin were administered to cells, and the effects were investigated
      by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and
      apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and
      theophylline induced apoptosis, and the treated cells expressed annexin V and
      caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however,
      hypoxanthine showed no effect. These results indicate that theophylline is
      similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by
      inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have
      anticancer effects and can improve the treatment effect in canine hemangiosarcoma
      patients. 

PMID- 23871417
TI  - Docetaxel and atrasentan versus docetaxel and placebo for men with advanced
      castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial.
AB  - BACKGROUND: The endothelin pathway has a role in bone metastases, which are
      characteristic of advanced prostate cancer. Atrasentan, an endothelin receptor
      antagonist, has shown activity in prostate cancer. We therefore assessed its
      effect on survival in patients with castration-resistant prostate cancer with
      bone metastases. METHODS: In a double-blind phase 3 trial, men with metastatic
      castration-resistant prostate cancer, stratified for progression type (prostate
      specific antigen or radiological), baseline pain, extraskeletal metastases, and
      bisphosphonate use, were randomly assigned in a 1:1 ratio to docetaxel (75
      mg/m(2) every 21 days, intravenously) with atrasentan (10 mg/day, orally) or
      placebo for up to 12 cycles and treated until disease progression or unacceptable
      toxicity. Patients who did not progress on treatment were permitted to continue
      atrasentan or placebo for up to 52 weeks. Coprimary endpoints were progression
      free survival (PFS) and overall survival. Analysis was by intention to treat.
      This trial is registered with ClinicalTrials.gov, number NCT00134056. FINDINGS:
      498 patients were randomly assigned to the atrasentan group and 496 to the
      placebo group. The trial was halted early for futility in April, 2011, after a
      planned interim analysis. Median PFS was 9.2 months (95% CI 8.5-9.9) in the
      atrasentan group and 9.1 months (8.4-10.2) in the placebo group (hazard ratio
      1.02, 0.89-1.16; p=0.81). Median overall survival was 17.8 months (16.4-19.8) in
      the atrasentan group versus 17.6 months (16.4-20.1) in the placebo group (1.04,
      0.90-1.19; p=0.64). 278 (57%) of 492 patients in the atrasentan group had grade 3
      and greater toxicity compared with 294 (60%) of 486 in the placebo group
      (p=0.22). Three deaths in the atrasentan group and seven in the placebo group
      were judged to be possibly or probably due to protocol treatment. INTERPRETATION:
      Atrasentan, when added to docetaxel, does not improve overall survival or PFS in
      men with castration-resistant prostate cancer and bone metastases; therefore,
      single-agent docetaxel should remain as one of the standard treatments. FUNDED:
      National Cancer Institute, Sanofi-Aventis, and Abbott Laboratories.

PMID- 23871420
TI  - Molecular detection of porcine kobuviruses in Italian swine.
AB  - In this study, fecal specimens (n=260) collected from Italian healthy pigs aged
      between 6 and 10 months were screened by RT-PCR using generic kobuvirus primers.
      Porcine kobuviruses (PKVs) were detected in 3.85% of the samples tested. Based on
      the analysis of the partial 3D gene, the Italian sequences identified here were
      more closely related to PKVs previously identified in Japan, Thailand, Korea,
      China and Brazil than to the European PKVs recently detected in Hungary and in
      the Netherlands.

PMID- 23871421
TI  - Long-term consequences of posterior urethral valves.
AB  - Posterior urethral valves (PUV) are the most common congenital cause of bladder
      outlet obstruction in infancy, and it is the effect of this obstruction on the
      bladder and the kidneys that will decide a patient's prognosis. With the
      improvements in diagnosis and treatments, what was previously a poor prognosis
      for boys with PUV has improved, and more patients will encounter the long-term
      sequelae of PUV during puberty and adulthood. In these patients the long-term
      prognosis in terms of renal and bladder function and fertility, as well as the
      risk of malignancy in those whose bladders were augmented with gastrointestinal
      segments, is still a matter of great concern and all of these topics will be
      discussed in this article. 

PMID- 23871422
TI  - Compensation to whole body active rotation perturbation.
AB  - The aim of the present study is the exploration of the compensation mechanisms in
      healthy adults elicited by superimposing a horizontal perturbation, through a
      rotation of the support base, during a whole body active rotation around the
      participant's own vertical body axis. Eight healthy participants stood on a
      rotating platform while executing 90 degrees  whole body rotations under three
      conditions: no concurrent platform rotation (NP), support surface rotation of +/-
      45 degrees  in the same (45-S) and opposite (45-O) directions. Participants'
      kinematics and CoP displacements were analyzed with an optoelectronic system and
      a force platform. In both 45-S and 45-O conditions, there was a tendency for the
      head to be affected by the external perturbation and to be the last and least
      perturbed segment while the pelvis was the most perturbed. The observed reduced
      head perturbation in 45-S and 45-O trials is consistent with a goal-oriented
      strategy mediated by vision and vestibular information, whereas the tuning of
      lumbar rotation is consistent with control mechanisms mediated by somato-sensory
      information.

PMID- 23871423
TI  - Lamellar ichthyosis in a collodion baby caused by CYP4F22 mutations in a non
      consanguineous family outside the Mediterranean.

PMID- 23871424
TI  - Sweat constitutes several natural moisturizing factors, lactate, urea, sodium,
      and potassium.
AB  - BACKGROUND: Amino acids (AAs) play important roles in maintaining an optimal
      hydration state of stratum corneum (SC) as a natural moisturizing factor (NMF).
      Recently, however, we have reported that lactate and potassium significantly
      affect the hydration state of SC. OBJECTIVE: To explore the source of lactate and
      potassium in SC, we compared the concentration of various NMFs such as AAs,
      pyrrolidone carbonic acid (PCA), lactate, sodium, and potassium in SC between
      anhidrotic and adjacent hidrotic areas of patients with acquired idiopathic
      generalized anhidrosis or segmental anhidrosis. METHODS: We examined 13
      anhidrotic areas and the adjacent hidrotic skin of 10 different patients. We
      first determined anhidrotic and hidrotic areas of each patient by the iodine
      starch method and examined the hydration state of SC by measuring the high
      frequency conductance. Then we obtained SC by tape stripping and measured the
      content of AAs, PCA, lactate, urea, sodium, and potassium in SC obtained from the
      anhidrotic and hidrotic areas. We examined the effect of increased insensible
      perspiration on the SC hydration and the concentrations of NMFs. RESULTS: The SC
      of anhidrotic areas showed significantly low hydration. Among NMFs, lactate,
      urea, sodium, and potassium were significantly decreased in the SC of anhidrotic
      areas, while AAs and PCA were not significantly different between hidrotic and
      anhidrotic areas. Increased insensible perspiration increased SC hydration as
      well as NMFs other than AAs and PCA. CONCLUSION: Sweat constitutes lactate, urea,
      sodium, and potassium in NMFs and plays a crucial role in maintaining the
      physiological hydration state of SC.

PMID- 23871425
TI  - Examining the value of lexical retrieval treatment in primary progressive
      aphasia: two positive cases.
AB  - Individuals with primary progressive aphasia (PPA) suffer a gradual decline in
      communication ability as a result of neurodegenerative disease. Language
      treatment shows promise as a means of addressing these difficulties but much
      remains to be learned with regard to the potential value of treatment across
      variants and stages of the disorder. We present two cases, one with semantic
      variant of PPA and the other with logopenic PPA, each of whom underwent treatment
      that was unique in its focus on training self-cueing strategies to engage
      residual language skills. Despite differing language profiles and levels of
      aphasia severity, each individual benefited from treatment and showed maintenance
      of gains as well as generalization to untrained lexical items. These cases
      highlight the potential for treatment to capitalize on spared cognitive and
      neural systems in individuals with PPA, improving current language function as
      well as potentially preserving targeted skills in the face of disease
      progression. 

PMID- 23871426
TI  - Device-associated healthcare-associated infections in the neonatal intensive care
      unit.

PMID- 23871427
TI  - Reconstruction of a soft tissue defect in the finger using the heterodigital
      neurocutaneous island flap.
AB  - BACKGROUND: This article describes reconstruction of a soft tissue defect in the
      finger using the heterodigital neurocutaneous island flap and reports the results
      of the use of the flap. METHODS: From February of 2008 to March of 2011, the
      neurocutaneous island flap was used in 12 patients with soft tissue defects in
      the middle phalanx or the proximal interphalangeal joint, or both. The injured
      fingers included 4 index, 3 middle, 3 ring and 2 little fingers. The donor
      fingers included 7 middle fingers and 5 ring fingers. The mean size of soft
      tissue defects and the flaps was 2.4 cm * 1.8 cm and 2.7 cm * 2.0 cm,
      respectively. The mean pedicle length was 2.8 cm. RESULTS: Full flap survival was
      achieved in 11 cases. Partial distal flap necrosis was noted in one case, which
      healed without surgical intervention. At a mean follow-up of 22 months, the mean
      static 2-point discrimination and Semmes-Weinstein monofilament scores on the
      flap were 8.3mm and 3.94, respectively. Based on the modified American Society
      for Surgery of the Hand guidelines for stratification of 2-point discrimination,
      10 (83%) of 12 flaps achieved good results. According to the Michigan Hand
      Outcomes Questionnaire, 5 patients were strongly satisfied and 7 were satisfied
      with functional recovery of the reconstructed finger. CONCLUSIONS: The
      neurocutaneous island flap of the dorsal branch of the digital nerve is useful,
      reliable, and technically easy for reconstructing a defect in the adjacent
      fingers, especially when sensory reconstruction is needed.

PMID- 23871428
TI  - The analysis of the variables, affecting outcome in surgically treated tibia
      pilon fractured patients.
AB  - INTRODUCTION: Treatment of tibia pilon fractures is challenging. Outcome after
      tibia pilon fractures depend on multiple factors. Aim of this study is to
      evaluate the potential variables that are known to affect the outcome after tibia
      pilon fractures. PATIENTS AND METHODS: Forty patients with 42 tibia pilon
      fractures with a one-year follow-up, who had undergone surgical treatment between
      January 2007 and June 2011, were evaluated, retrospectively. Patients were
      divided into 3 groups regarding the choice of surgical treatment (Group A-22
      patients treated with open reduction-internal fixation; Group B-9 patients
      treated with mini-open reduction-internal fixation and external fixation; and
      Group C-11 patients treated with closed reduction-external fixation). Fractures
      were classified using Muller-AO and Ruedi/Allgower classifications. Quality of
      reduction was evaluated using Ovadia and Beals' criteria. All patients underwent
      functional assessment using AOFAS ankle-hindfoot scale and Teeny-Wiss scoring
      system at the last follow-up. RESULTS: Mean age of the patients was 49 (20-80).
      There were eight 43-B3, six 43-C1, twelve 43-C2 and sixteen 43-C3 fractures
      according to Muller-AO classification and ten type 1, ten type 2 and twenty two
      type 3 fractures according to Ruedi/Allgower classification. There were 15
      (35.7%) open fractures. No statistically significant relation was found between
      quality of reduction and type of surgery. Also no significant relation was found
      between the type of surgery and functional scores. No significant correlation was
      found between functional scores and Muller-AO classification, but functional
      scores were found significantly worse in Ruedi/Allgower type 3 fractures.
      Functional scores were found significantly related to the quality of reduction.
      Early complications were seen in 22 and late complications were seen in 9
      fractures. No statistically significant relation was found between complications,
      type of surgery and functional scores. CONCLUSION: The most important factor
      affecting outcome in surgically treated tibia pilon fractures was quality of
      reduction. Poor functional scores were found independent from the type of surgery
      and quality of reduction in Ruedi/Allgower type 3 fractures, which was
      characterized with articular surface comminution and metaphyseal impaction.

PMID- 23871429
TI  - A computer scientist's view on mobile DNA: comment on "How life changes itself:
      the Read-Write (RW) genome" by James Shapiro.

PMID- 23871430
TI  - Towards a modern view of the dynamic genome: comment on "How life changes itself:
      The Read-Write (RW) genome" by James Shapiro.

PMID- 23871431
TI  - Evolution: life has evolved to evolve: comment on "How life changes itself: the
      Read-Write (RW) genome" by James Shapiro.

PMID- 23871432
TI  - Was Zeus responsible for horizontal gene transfer: a comment on "Lightning
      triggered electroporation and electrofusion as possible contributors to natural
      horizontal gene transfer" by Tadej Kotnik.

PMID- 23871433
TI  - Influence of age at diagnosis on glycaemic control evolution in patients with
      type 1 diabetes.
AB  - AIM: The objective of this study was to describe the relationship between age at
      onset, with no age limits, and glycaemic control evolution from the time of onset
      in patients with type 1 diabetes (T1D). METHODS: This observational retrospective
      follow-up study included 716 patients with T1D onset between 1990 and 2008
      treated at the Navarre Hospital Complex. The mean (SD) follow-up lasted 10.1
      (5.3) years. Information on their HbA(1c) levels was collected at onset and every
      year thereafter. Generalized additive mixed models and linear models were used,
      with patients' annual HbA1c levels as the response variable and the number of
      years since onset together with age at onset as covariates. RESULTS: The
      evolution of glycaemic control is not linear and differs across all age groups.
      Children reach their highest values in adolescence, while patients with onset at
      ages 10-15 years stabilize their HbA(1c) values after 7 or 8 years. In adults, it
      is notable that an age of onset >= 45 years is associated with the worst control.
      CONCLUSION: A non-linear increase in HbA(1c) levels can be observed from the time
      of T1D diagnosis, with significant differences across all age groups.

PMID- 23871434
TI  - WIP1, a homeostatic regulator of the DNA damage response, is targeted by HIPK2
      for phosphorylation and degradation.
AB  - WIP1 (wild-type p53-induced phosphatase 1) functions as a homeostatic regulator
      of the ataxia telangiectasia mutated (ATM)-mediated signaling pathway in response
      to ionizing radiation (IR). Here we identify homeodomain-interacting protein
      kinase 2 (HIPK2) as a protein kinase that targets WIP1 for phosphorylation and
      proteasomal degradation. In unstressed cells, WIP1 is constitutively
      phosphorylated by HIPK2 and maintained at a low level by proteasomal degradation.
      In response to IR, ATM-dependent AMPKalpha2-mediated HIPK2 phosphorylation
      promotes inhibition of WIP1 phosphorylation through dissociation of WIP1 from
      HIPK2, followed by stabilization of WIP1 for termination of the ATM-mediated
      double-strand break (DSB) signaling cascade. Notably, HIPK2 depletion impairs IR
      induced gamma-H2AX foci formation, cell-cycle checkpoint activation, and DNA
      repair signaling, and the survival rate of hipk2+/- mice upon gamma-irradiation
      is markedly reduced compared to wild-type mice. Taken together, HIPK2 plays a
      critical role in the initiation of DSB repair signaling by controlling WIP1
      levels in response to IR.

PMID- 23871435
TI  - Effectiveness of a parenting program in Bangladesh to address early childhood
      health, growth and development.
AB  - A stratified cluster design was used to evaluate a 10-month parenting program
      delivered to mothers of children in rural Bangladesh. Intervention mothers
      through a combination of group meetings and home visits received messages along
      with an illustrative card concerning hygiene, responsive feeding, play,
      communication, gentle discipline, and nutritious foods. Control mothers received
      the standard government care. Three months prior, 463 children between 4 and 14
      months in a subdistrict of western Bangladesh were administered the cognitive,
      receptive language and expressive language Bayley III subtests, their length was
      taken and past week illness recorded. Gross motor milestones were reported by the
      mother and verified through observation. Mothers were interviewed concerning
      their practices: preventive health practices, dietary diversity, home
      stimulation, and knowledge about development milestones. Maternal depressive
      symptoms were assessed as a measure of emotional availability. Family
      sociodemographic variables included maternal education, family assets, decision
      making and mobility autonomy. One month after the end of the program, mothers and
      their children were again assessed. Comparisons were made between intervention
      and control children who were under-12 months vs. 12 months and older at the
      start of the program. This may be a critical age, when children begin to be
      upright and mobile enough to explore on their own and be less dependent on
      parenting stimulation. Analyses yielded strong intervention effects on the three
      Bayley subtests and on parenting practices related to stimulation and knowledge
      of development milestones. Age effects were found only for dietary diversity in
      that younger children in the program benefited more than older ones. However, all
      children became more stunted. Findings are discussed in terms of theories of
      behaviour change and parenting, critical ages for parenting programs, and
      implications for program delivery. 

PMID- 23871436
TI  - Bridging integrator 1 (BIN1): form, function, and Alzheimer's disease.
AB  - The bridging integrator 1 (BIN1) gene, also known as amphiphysin 2, has recently
      been identified as the most important risk locus for late onset Alzheimer's
      disease (LOAD), after apolipoprotein E (APOE). Here, we summarize the known
      functions of BIN1 and discuss the polymorphisms associated with LOAD, as well as
      their possible physiological effects. Emerging data suggest that BIN1 affects AD
      risk primarily by modulating tau pathology, but other affected cellular functions
      are discussed, including endocytosis/trafficking, inflammation, calcium
      homeostasis, and apoptosis. Epigenetic modifications are important for AD
      pathogenesis, and we review data that suggests the possible DNA methylation of
      the BIN1 promoter. Finally, given the potential contributions of BIN1 to AD
      pathogenesis, targeting BIN1 might present novel opportunities for AD therapy. 

PMID- 23871437
TI  - Echocardiographic assessment of cardiac performance in response to high altitude
      and development of subclinical pulmonary edema in healthy climbers.
AB  - BACKGROUND: Data regarding the effect of high altitude on heart function are
      sparse and conflicting. We aimed to assess the right and left ventricular
      responses to altitude-induced hypoxia and the occurrence of subclinical pulmonary
      edema. METHODS: Echocardiography was performed according to protocol on 14
      subjects participating in an expedition in Nepal, at 3 altitude levels: Montreal
      (30 m), Namche Bazaar (3450 m), and Chukkung (4730 m). Systematic lung ultrasound
      was performed to detect ultrasound lung comets. RESULTS: Pulmonary artery
      systolic pressure increased in all subjects between Montreal and Chukkung (mean
      27.4 +/- 5.4 mm Hg vs. 39.3 +/- 7.7 mm Hg; P < 0.001). Right ventricular (RV)
      myocardial performance index (MPI) increased significantly (0.32 +/- 0.08 at 30 m
      vs. 0.41 +/- 0.10 at 4730 m; P = 0.046). A trend toward deteriorated RV free wall
      longitudinal strain was observed between Montreal and Chukkung (-25.9 [5.3%] vs. 
      21.9 [6.4%]; P = 0.092). The left ventricular early diastolic inflow
      velocity/atrial mitral inflow velocity and early diastolic inflow velocity/mean
      of the maximal early diastolic mitral annulus tissue doppler velocities ratios
      remained unchanged. At 4730 m, ultrasound lung comets were seen in all subjects
      except 1. None had clinical criteria for high-altitude pulmonary edema (HAPE).
      All altered parameters normalized after return to sea level. CONCLUSION:
      Subclinical HAPE is frequent in healthy lowlander climbers. This is the first
      study to document a trend towards decreased RV free wall strain and MPI increment
      at high altitude. Whether rising RV MPI is a physiologic adaptive mechanism to
      hypoxia or a pathologic response identifying HAPE-susceptible subjects needs
      further study.

PMID- 23871438
TI  - To con protection: TIR-domain containing proteins (Tcp) and innate immune
      evasion.
AB  - The innate immune system provides the host's first line of defence against
      invading pathogens. Key to the stimulation of the innate immune response is
      pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs), which
      recognize microbial-associated molecular patterns (MAMPs). Binding of MAMPs to
      TLRs triggers a signalling cascade resulting in the production of pro
      inflammatory mediators. Central to this TLR signalling pathway are heterotypic
      protein-protein interactions mediated through Toll/interleukin-1 receptor (TIR)
      domains found in both the cytoplasmic regions of TLRs and several key adaptor
      proteins. Interestingly, TIR-domain containing proteins (Tcps) do not seem to be
      unique to the mammalian TLR system, but occurs in abundance in many biological
      forms. Recent evidence suggests that pathogenic bacteria have developed a range
      of ingenuous strategies to evade the host immune mechanisms involving Tcps. There
      is increasing evidence to suggest that these pathogen-encoded Tcps interfere
      directly with the TLR signalling pathway and thus inhibit the activation of NF
      kappaB, with different modes of action and roles in virulence. Here, we review
      the current state of knowledge on the possible roles and mechanisms of action of
      bacterial encoded Tcp. 

PMID- 23871439
TI  - Interdisciplinary palliative care intervention in metastatic non-small-cell lung
      cancer.
AB  - OBJECTIVE: Challenges and barriers continue to hinder the integration of
      palliative care models into comprehensive, ambulatory oncology care. This article
      aims to describe how symptoms, distress, and quality of life (QOL) data from the
      usual care phase of a National Cancer Institute-supported Program Project
      informed the development of an interdisciplinary, tailored palliative care
      intervention for patients with metastatic non-small-cell lung cancer (NSCLC).
      METHODS: Patients receiving usual care for metastatic NSCLC were recruited into
      this prospective longitudinal study over a 1-year period. A total of 130 patients
      with stage IV NSCLC were accrued, and 114 patients had evaluable data. Research
      nurses assisted patients in completing the clinical section of the data forms,
      and patients completed surveys and self-reports at baseline and 6, 12, and 24
      weeks. RESULTS: Patients ranged in age from 40 to 84 years, and 61% were
      Caucasian non-Hispanic. Sixty-six former (N = 59) and current smokers had an
      average of 38 pack-year history of smoking. The Karnofsky Performance Status,
      Instrumental Activities of Daily Living, and Cognitive scores deteriorated
      significantly (P = .001, .009, and .042, respectively). Social Activity was
      stable, whereas Social Support increased significantly. Overall symptom distress
      score and Total symptom score both significantly increased at 24 weeks (P = .003
      and .017, respectively). Physical Well-Being decreased significantly (P = .036),
      whereas the Functional Assessment of Cancer Therapy-Lung, Functional Assessment
      of Chronic Illness Therapy-Spirituality Subscale, and Distress scores remained
      statistically stable over time. CONCLUSIONS: Patients with metastatic NSCLC
      continue to experience high symptom burden and diminished physical well-being
      over time while receiving cancer treatments. An interdisciplinary palliative care
      intervention is currently being tested to improve symptom burden and overall QOL.

PMID- 23871440
TI  - Efficacy of centhaquin as a small volume resuscitative agent in severely
      hemorrhaged rats.
AB  - Centhaquin has been reported to be an effective resuscitative agent. The present
      study was carried out to determine resuscitative effect of centhaquin when
      administered using a small volume of 3% hypertonic saline (HS) to hemorrhaged
      rats. Sprague-Dawley rats were anesthetized with urethane, and a pressure
      catheter SPR-320 was placed in the left femoral artery; another pressure-volume
      catheter SPR-869 was placed into the left ventricle. Hemorrhage was induced by
      withdrawing blood and mean arterial pressure (MAP) was maintained at 35 mm Hg for
      30 minutes after which resuscitation was performed. Animals were divided in 2
      groups: group A received HS and group B received centhaquin (0.05 mg/kg)
      dissolved in HS. The time by which MAP fell back to 35 mm Hg was observed at that
      time all animals were administered fresh blood. It was found that centhaquin
      significantly reduced blood lactate and improved cardiac output and MAP of
      hemorrhaged rats compared with HS. The time by which MAP fell back to 35 mm Hg in
      rats treated with HS was 55 +/- 6 minutes, whereas it was 161 +/- 14 minutes in
      centhaquin treated rats. Survival time following administration of fresh blood
      was 79 +/- 7 minutes in vehicle-treated group, whereas it was 105 +/- 9 minutes
      in centhaquin-treated rats. The total time of survival of rats treated with HS or
      centhaquin was 134 +/- 12 minutes and 266 +/- 16 minutes, respectively.
      Centhaquin, in small volume, maintained MAP of hemorrhaged rats for a
      considerable long time and improved the survival time. 

PMID- 23871441
TI  - [Subdural block and Horner's syndrome].

PMID- 23871442
TI  - Defining the key pharmacophore elements of PF-04620110: discovery of a potent,
      orally-active, neutral DGAT-1 inhibitor.
AB  - DGAT-1 is an enzyme that catalyzes the final step in triglyceride synthesis. mRNA
      knockout experiments in rodent models suggest that inhibitors of this enzyme
      could be of value in the treatment of obesity and type II diabetes. The
      carboxylic acid-based DGAT-1 inhibitor 1 was advanced to clinical trials for the
      treatment of type 2 diabetes, despite of the low passive permeability of 1.
      Because of questions relating to the potential attenuation of distribution and
      efficacy of a poorly permeable agent, efforts were initiated to identify
      compounds with improved permeability. Replacement of the acid moiety in 1 with an
      oxadiazole led to the discovery of 52, which possesses substantially improved
      passive permeability. The resulting pharmacodynamic profile of this neutral DGAT
      1 inhibitor was found to be similar to 1 at comparable plasma exposures. 

PMID- 23871443
TI  - Antitumor properties of substituted (alphaE)-alpha-(1H-indol-3
      ylmethylene)benzeneacetic acids or amides.
AB  - A novel class of indole derivatives characterized by a (alphaE)-alpha-(1H-indol-3
      ylmethylene)benzeneacetic acid or amide scaffold was synthesized. These
      derivatives, assayed for cell-growth inhibition activity against a panel of six
      different tumor cell lines, showed strong antiproliferative activity and
      selectivity mainly towards DU145 cell line. In particular, compounds 2d-m and 5
      stand out for their cell growth inhibitory activity and, among them, compound 2d
      emerged for its selectivity towards DU145 with respect to other tested tumor cell
      lines. DU145 treated with 1MUM of 2d for 72h showed p21(Cip1) induction and
      suppression of Akt signaling together with induction of Rb. From a computational
      point of view, two different approaches were used in order to study topology and
      electronic properties of the novel compounds and to shed light on their drug
      likeness properties. Firstly, topological and electronic features of the
      compounds endowed with the most relevant biological activity were deepened; in
      parallel, some ADME properties like solubility and permeability were predicted. 

PMID- 23871444
TI  - Attacking cancer with molecularly targeted agents.

PMID- 23871445
TI  - Novel pathways in the yin-yang of immunomodulation.

PMID- 23871446
TI  - Targeting advanced glycation endproducts and mitochondrial dysfunction in
      cardiovascular disease.
AB  - Cardiovascular disease (CVD) is a leading cause of mortality in the Western
      World. The development and onset of disease can be attributed to many risk
      factors including genetic susceptibility, diabetes, obesity and atherosclerosis.
      Numerous studies highlight the production of advanced glycation endproducts
      (AGEs) and interaction with their receptor (RAGE) as playing a key pathogenic
      role. The AGEs-RAGE axis is thought to contribute to a proinflammatory
      environment inducing cellular dysfunction which cascades towards pathology.
      Mitochondrial dysfunction concurrently plays a role in these proinflammatory
      responses presenting excess reactive oxygen species (ROS) production under
      pathological conditions. This ROS release can exacerbate the production of AGEs
      fuelling the fire somewhat. However, the AGEs-RAGE axis may influence
      mitochondrial function independently of inflammation. Therefore instigation of
      the AGEs-RAGE axis may facilitate spiralling towards pathology on many fronts
      including CVD development. 

PMID- 23871448
TI  - Altered cortical gyrification patterns in panic disorder: deficits and potential
      compensation.
AB  - Abnormal gyrification patterns may reflect aberrant cortical connectivity during
      an early period of brain maturation. We here investigated anatomical distribution
      of cortical gyrification deficits underlying panic disorder and the relationships
      of these potential neurodevelopmental markers with panic symptom severity. High
      resolution three-dimensional T1-weighted structural images were obtained from 23
      patients with panic disorder and 33 matched healthy individuals. Local
      gyrification indices were measured in each genetically-based parcellated cortical
      subregion and regional gyrification patterns were compared between groups.
      Cortical areas in which gyrification patterns were associated with panic symptom
      severity were also determined. Significant reductions in cortical gyrification
      were observed in panic patients compared with healthy individuals, which were
      mainly distributed in the lateral brain extending from the fronto-parietal to the
      temporal areas. In contrast, hyper-gyrification in the posteromedial cortical
      regions which exert interconnecting roles in the default mode network, was
      associated with less severe panic symptoms. Post-hoc analysis for the inter
      regional covariance of local gyrification indices revealed that interconnections
      of the posteromedial cortical regions with other cortical areas which belong to
      the default mode network were reduced in panic patients with severe symptoms
      relative to either less severe patients or healthy individuals. Our findings
      suggest not only substantial perturbation in cortical gyrification patterns in
      panic disorder but also potential contribution of integrated cortical folding
      pattern of the default mode network to alleviated panic severity. 

PMID- 23871447
TI  - Intussusception incidence among infants in the UK and Republic of Ireland: a pre
      rotavirus vaccine prospective surveillance study.
AB  - INTRODUCTION: Intussusception, an abdominal emergency in young children, has been
      linked to a previous vaccine used to prevent rotavirus gastroenteritis. Although
      this vaccine was withdrawn, recent studies have suggested a potential, very small
      increased risk of intussusception following the administration of newly developed
      rotavirus vaccines. We aimed to determine the baseline incidence of
      intussusception among infants in the UK and Republic of Ireland - prior to the
      imminent introduction of the rotavirus vaccine into the UK schedule this year.
      METHODS: Prospective, active surveillance via the established British Paediatric
      Surveillance Unit (BPSU) was carried out from March 2008 to March 2009.
      Clinicians across 101 National Health Service (and equivalent) hospitals,
      including 27 paediatric surgical centres, reported cases admitted for
      intussusception in the UK and Republic of Ireland. The standard Brighton
      Collaboration case definition was used with only definite cases included for
      incidence estimation. RESULTS: The study response rate was 94.5% (379
      questionnaires received out of 401 case notifications). A total of 250 definite
      cases of intussusception were identified. The annual incidence among infants in
      the UK and Republic of Ireland was 24.8 (95% CI: 21.7-28.2) and 24.2 (95% CI:
      15.0-37.0) per 100,000 live births. In the UK, the highest incidence occurred in
      Northern Ireland (40.6, 95% CI: 21.0-70.8), followed by Scotland (28.7, 95% CI:
      17.5-44.3), England (24.2, 95% CI: 20.9-27.9), then Wales (16.9, 95% CI: 6.8
      34.8). In England, regional incidence was highest in London and lowest in the
      West Midlands. By age, the highest incidence (50.3/100,000 live births, 95% CI:
      33.4-72.7) occurred in the fifth month of life (for England). A seasonal trend in
      the presentation of intussusception was observed with the incidence significantly
      (p=0.001) increased during winter and spring. CONCLUSION: The baseline rates
      obtained in this study will inform rotavirus vaccine-safety policy by enabling
      comparison with post-introduction incidence.

PMID- 23871449
TI  - The interaction of affective with psychotic processes: a test of the effects of
      worrying on working memory, jumping to conclusions, and anomalies of experience
      in patients with persecutory delusions.
AB  - Worry has traditionally been considered in the study of common emotional
      disorders such as anxiety and depression, but recent studies indicate that worry
      may be a causal factor in the occurrence and persistence of persecutory
      delusions. The effect of worry on processes traditionally associated with
      psychosis has not been tested. The aim of the study was to examine the short-term
      effects of a bout of worry on three cognitive processes typically considered
      markers of psychosis: working memory, jumping to conclusions, and anomalous
      internal experience. Sixty-seven patients with persecutory delusions in the
      context of a non-affective psychotic disorder were randomised to a worry
      induction, a worry reduction, or a neutral control condition. They completed
      tests of the cognitive processes before and after the randomisation condition.
      The worry induction procedure led to a significant increase in worry. The
      induction of worry did not affect working memory or jumping to conclusions, but
      it did increase a range of mild anomalous experiences including feelings of
      unreality, perceptual alterations, and temporal disintegration. Worry did not
      affect the occurrence of hallucinations. The study shows that a period of worry
      causes a range of subtle odd perceptual disturbances that are known to increase
      the likelihood of delusions. It demonstrates an interaction between affective and
      psychotic processes in patients with delusions. 

PMID- 23871451
TI  - Virus infections: T cells come to the rescue.

PMID- 23871452
TI  - Cerebral amyloid angiopathy causing cortical microinfarction.
AB  - Cerebral amyloid angiopathy as a cause of recurrent small cortical strokes is
      under-recognised. These patients need haemosiderin-sensitive MRI to make a
      diagnosis and intensive antiplatelet treatment is dangerous. 

PMID- 23871450
TI  - CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor
      imaging study.
AB  - CNTNAP2 is a gene on chromosome 7 that has shown associations with autism and
      schizophrenia, and there is evidence that it plays an important role for neuronal
      synchronization and brain connectivity. In this study, we assessed the
      relationship between Diffusion Tensor Imaging (DTI), a putative marker of
      anatomical brain connectivity, and multiple single nucleotide polymorphisms
      (SNPs) spread out over this large gene. 81 healthy controls and 44 patients with
      schizophrenia (all Caucasian) underwent DTI and genotyping of 31 SNPs within
      CNTNAP2. We employed Tract-based Spatial Statistics (TBSS) for inter-subject
      brain registration and computed average diffusivity values for six major white
      matter tracts. Analyses of Covariance (ANCOVAs) were computed to test for
      possible associations with genotypes. The strongest association, which survived
      rigorous Bonferroni correction, was between rs2710126 genotype and Fractional
      Anisotropy (FA) in the uncinate fasciculus (p = .00003). This anatomical location
      is particularly interesting given the enriched fronto-temporal expression of
      CNTNAP2 in the developing brain. For this SNP, no phenotype association has been
      reported before. There were several further genotype-DTI associations that were
      nominally significant but did not survive Bonferroni correction, including an
      association between axial diffusivity in the dorsal cingulum bundle and a region
      in intron 13 (represented by rs2710102, rs759178, rs2538991), which has
      previously been reported to be associated with anterior-posterior functional
      connectivity. We present new evidence about the effects of CNTNAP2 on brain
      connectivity, whose disruption has been hypothesized to be central to
      schizophrenia pathophysiology.

PMID- 23871453
TI  - Successful surgical treatment of intractable spontaneous intracranial hypotension
      due to a calcified thoracic disc prolapse.
AB  - We present a patient with spontaneous intracranial hypotension due to a calcified
      thoracic disc prolapse. Although most cases of spontaneous intracranial
      hypotension resolve with conservative measures, a few reported patients require
      surgical intervention. We discuss an uncommon presentation of spontaneous
      intracranial hypotension, requiring surgical repair of a thoracic dural defect to
      achieve symptom resolution. 

PMID- 23871454
TI  - Cervical disc arthroplasty for the treatment of spondylotic myelopathy and
      radiculopathy.
AB  - The concept of cervical disc arthroplasty (CDA) for the anterior treatment of
      cervical pathology has existed for approximately half a decade. In this time,
      multiple devices have been developed for this purpose, with the ultimate aim to
      provide an alternative to fusion. Fifty-five patients with cervical spondylotic
      radiculopathy and myelopathy underwent CDA over a 5 year period. Data was
      collected on 46 patients, which included Visual Analogue Scale scores for neck
      pain and arm pain, Neck Disability Index scores, Short Form-36 v2 (SF-36) and
      Nurick grades for myelopathy patients. Preoperative data and data obtained at the
      latest clinical follow-up (median 48 months, range, 10-76 months) were analysed
      to assess the intermediate term efficacy of the procedure. In patients with
      radiculopathy, arm pain improved by 88% (p<0.001). In those presenting with
      myelopathy, the Nurick grades improved from a median of 1 to 0 (p<0.001). In both
      groups of patients, improvements in pain and neurologic deficit were accompanied
      by significant improvements in multiple domains of the SF-36. Using a composite
      system which considered neck pain, arm pain, function and myelopathy, we arrived
      at an overall success rate of 73%. We concluded that CDA is an effective
      intervention for improving neurologic deficit, arm pain and local neck symptoms
      that translated into improvements in physical and social functioning in the
      intermediate term.

PMID- 23871455
TI  - Population structure and characterisation of Staphylococcus aureus from
      bacteraemia at multiple hospitals in China: association between antimicrobial
      resistance, toxin genes and genotypes.
AB  - Staphylococcus aureus from bacteraemia at multiple hospitals in China were
      genetically characterised to improve understanding of its epidemiology. A total
      of 236 consecutive, non-duplicate S. aureus bacteraemia isolates were collected
      at 16 Chinese hospitals. Isolates were characterised by antimicrobial resistance,
      19 toxin genes, agr alleles, multilocus sequence typing and spa typing. The
      prevalence of meticillin-resistant S. aureus (MRSA) was 47.5% (112/236). Forty
      two sequence types (STs) and 63 spa types were identified, including 14 STs and
      14 spa types for MRSA. Clonal complex (CC) 8, CC5, ST7 and CC188 accounted for
      67.4% of the isolates. ST239-t030/t037-SCCmecIII-agrI was the predominant MRSA
      genotype (50%), followed by ST5-t002/t570-SCCmecII-agrII (8%). A vancomycin MIC
      >= 1mg/L was detected significantly more often in ST5-SCCmecII and ST239-t037
      SCCmecIII, whereas rifampicin resistance was overwhelmingly associated with ST239
      t030-SCCmecIII (P<0.001). Oxacillin MICs were relatively low for ST59-MRSA. Major
      genotypes of meticillin-susceptible S. aureus (MSSA) were ST7-t091/t796-agrI
      (16.1%), ST188-t189-agrI (12.1%) and ST398-t571/t034-agrI (5.6%). Toxin genes
      were identified in 95.8% of isolates and formed 89 toxin gene profiles. The toxin
      genes sea, selk, selq and sell were significantly more common in MRSA, whilst
      tsst-1, seb, sed, selm, seln, selp and selj were more prevalent in MSSA
      (P<0.001). The pvl gene was more commonly detected in CC59, whereas tsst-1 was
      more frequent in CC15, CC188 and ST398 (P<0.001). The major genotypes were
      associated with specific antimicrobial resistance and toxin gene profiles. 

PMID- 23871456
TI  - Which mechanisms of azithromycin resistance are selected when efflux pumps are
      inhibited?
AB  - The aim of this study was to develop in vitro azithromycin (AZM)-resistant
      mutants of Escherichia coli and Shigella spp. in the presence of Phe-Arg beta
      naphthylamide (PAbetaN) and to observe which AZM resistance mechanisms other than
      efflux pumps were inhibited by PAbetaN emerge. The frequency of mutation ranged
      between <6.32 * 10(-10) and 5.22 * 10(-7) for E. coli and between <5.32 * 10(-10)
      and 1.69 * 10(-7) for Shigella spp. The E. coli mutants showed an increase in the
      AZM minimum inhibitory concentration (MIC) up to 128-fold, whilst the Shigella
      spp. mutants presented increases in MIC levels of up to 8-fold. In one mutant,
      the insertion of nucleotides encoding the amino acid sequence IMPRAS was found in
      the rplV gene. Increases in OmpW expression were observed in all E. coli mutants
      compared with their respective parental isolates. The combination of antibiotics
      and efflux pump inhibitors appears to be a good option to reduce the frequency of
      mutation in clinical isolates.

PMID- 23871457
TI  - Comparison of NCHS, CDC, and WHO curves in children with cardiovascular risk.
AB  - OBJECTIVE: The study aimed to compare the prevalence of overweight and obesity
      according to three growth curves, created by the World Health Organization
      (WHO/2006), by the National Center for Health Statistics (NCHS/1977), and by the
      Centers for Disease Control and Prevention (CDC/2000) in children with
      cardiovascular risk factors. METHODS: Data from 118 children and adolescents,
      aged between 2 and 19 years, treated between the years 2001 to 2009 at the
      Pediatric Preventive Cardiology Outpatient Clinic of the Instituto de Cardiologia
      de Porto Alegre were evaluated. The variables analyzed were: weight, height, age,
      and gender. Variables were classified according to the following criteria:
      weight/age, height/age, and body mass index (BMI). The cutoff points used were
      obtained from the three growth curves: WHO/2006, NCHS/1977, and CDC/2000.
      RESULTS: Regarding the criterion weight/age by the NCHS curve, 18% of the
      children were classified as having normal weight, and 82% had excess weight; by
      the CDC curve, 28% had normal and 72% had excess weight; by the WHO curve, 16.0%
      had normal weight and 84% had excess weight. According to the BMI, 0.8% of the
      population was underweight. According to the CDC and WHO curves, 7.6% and 6.8%
      had normal weight; 26.3% and 11.9% were overweight; and 65.3% and 80.5% were
      obese, respectively. Regarding the height/age criterion, there was no significant
      difference between the references and, on average, 98.3% of the population showed
      adequate height for age. CONCLUSION: The new WHO curves are more sensitive to
      identify obesity in a population at risk, which has important implications for
      preventive and therapeutic management.

PMID- 23871459
TI  - Milia en plaque.

PMID- 23871458
TI  - [Development of external quality control protocol for CyberKnife beams dosimetry:
      preliminary tests multicentre].
AB  - PURPOSE: To develop an external quality control procedure for CyberKnife((r))
      beams. This work conducted in Nancy, has included a test protocol initially drawn
      by the medical physicist of Nancy and Lille in collaboration with Equal-Estro
      Laboratory. MATERIALS AND METHODS: A head and neck anthropomorphic phantom and a
      water-equivalent homogeneous cubic plastic test-object, so-called "MiniCube",
      have been used. Powder and solid thermoluminescent dosimeters as well as
      radiochromic films have been used to perform absolute and relative dose studies,
      respectively. The comparison between doses calculated by Multiplan treatment
      planning system and measured doses have been studied in absolute dose. The dose
      distributions measured with films and treatment planning system calculations have
      been compared via the gamma function, configured with different tolerance
      criteria. RESULTS: This work allowed, via solid thermoluminescent dosimeter
      measurements, verifying the beam reliability with a reproducibility of 1.7 %. The
      absolute dose measured in the phantom irradiated by the seven participating
      centres has shown an error inferior to the standard tolerance limits (+/- 5 %),
      for most of participating centres. The relative dose measurements performed at
      Nancy and by the Equal-Estro laboratory allowed defining the most adequate
      parameters for gamma index (5 %/2mm--with at least 95 % of pixels satisfying
      acceptability criteria: gamma<1). These parameters should be independent of the
      film analysis software. CONCLUSION: This work allowed defining a dosimetric
      external quality control for CyberKnife((r)) systems, based on a reproducible
      irradiation plan through measurements performed with thermoluminescent dosimeters
      and radiochromic films. This protocol should be validated by a new series of
      measurement and taking into account the lessons of this work.

PMID- 23871460
TI  - Nail histopathology.
AB  - The structure of the nail unit is complex and many dermatologists and
      dermatopathologists have an incomplete understanding of it. Familiarity with the
      anatomy and histology of this unit, however, is a key factor in improving the
      diagnostic yield of nail biopsy. Inflammatory or infectious conditions that
      affect the nail can have a marked impact on a patient's quality of life. A wide
      ranging variety of tumors can also develop in this region and they may be life
      threatening or require surgery that will result in functional defects. The author
      reviews the anatomy and histology of the nail unit as well as the basic
      histopathologic findings in the most common conditions affecting the nails. 

PMID- 23871461
TI  - [Blood transfusion practices: about transfusions at night].
AB  - Blood transfusion safety covers all stages from prescription of immuno
      haematological examinations until the completion of the transfusion. According to
      the 05/11/2006 Afssaps' decision on good transfusion practices, transfusions
      should not be given at night unless the patient is actively bleeding or has some
      other urgent clinical need. A retrospective study was used to assess the
      proportion of transfusions at night. Through this professional practice
      evaluation, we analyze the reasons leading to perform transfusions at late hours,
      in order to reduce errors and improve safety for patients. 

PMID- 23871462
TI  - [Management by objectives: an experience by transfusion and immunology service in
      Rabat].
AB  - The management by objectives method has become highly used in health management.
      In this context, the blood transfusion and haemovigilance service has been chosen
      for a pilot study by the Head Department of the Ibn Sina Hospital in Rabat. This
      study was conducted from 2009 to 2011, in four steps. The first one consisted in
      preparing human resources (information and training), identifying the strengths
      and weaknesses of the service and the identification and classification of the
      service's users. The second step was the elaboration of the terms of the
      contract, which helped to determine two main strategic objectives: to strengthen
      the activities of the service and move towards the "status of reference." Each
      strategic objective had been declined in operational objectives, then in actions
      and the means required for the implementation of each action. The third step was
      the implementation of each action (service, head department) so as to comply with
      the terms of the contract as well as to meet the deadlines. Based on assessment
      committees, the last step consisted in the evaluation process. This evaluation
      was performed using monitoring indicators and showed that management by
      objectives enabled the Service to reach the "clinical governance level", to
      optimize its human and financial resources and to reach the level of "national
      laboratory of reference in histocompatibility". The scope of this paper is to
      describe the four steps of this pilot study and to explain the usefulness of the
      management by objectives method in health management.

PMID- 23871463
TI  - Outcomes of screening Parkinson's patients for QTc prolongation.
AB  - BACKGROUND: Parkinson's disease (PD) patients are commonly prescribed medication
      that has recently been associated with QTc prolongation on electrocardiograms
      (ECG). In addition, research suggests that PD patients may be more at risk of QTc
      prolongation. OBJECTIVE: To evaluate the outcomes of screening PD patients for
      QTc prolongation. METHODS: ECG analysis of PD patients attending for routine
      outpatient PD review in 2012 who were prescribed medication that could
      potentially prolong their QTc interval. We noted prescribing changes and any
      repeat ECG findings. We also reviewed any recent ECGs of clinic patients not on
      QTc prolonging medication. RESULTS: A third of our PD clinic patients (63/192)
      were prescribed QTc prolonging medication. Of these 61/63 (97%) ECGs were
      available. 20/61 (33%) showed QTc prolongation. 6/20 (30%) had significant
      prolongation >500 ms. 18/20 (90%) patients had medication changes made, and of
      the 12/18 (67%) ECGs repeated in this group all improved with 11 demonstrating
      normalisation of the QTc interval. Of the 51 available ECGs in patients not
      prescribed QTc prolonging medication 3/51 (6%) showed QTc prolongation.
      Statistical analysis showed that QTc prolongation was significantly associated
      with the prescription of QTC prolonging medication and stage of PD. CONCLUSION:
      QTc prolongation in PD patients caused by medication is a major modifiable risk
      factor. A routine ECG should be considered if a PD patient is currently
      prescribed medication that can prolong the QTc interval. Also consideration
      should be given to performing this simple test prior to commencing QTc prolonging
      medication.

PMID- 23871464
TI  - Transcranial sonography in mitochondrial membrane protein-associated
      neurodegeneration.

PMID- 23871465
TI  - Cognitive impairment and polidistrectual atherosclerotic disease in
      chylomicronemia syndrome: a case report.
AB  - A case of chylomicronemia syndrome is reported in a 72-year-old male with
      distinctive features of chronic pancreatic damage, severe hypertriglyceridemia,
      polidistrectual atherosclerosis and premature cognitive impairment. Although the
      patient had a positive history for recurrent episodes of pancreatitis the
      characteristic lesions of the hyperchylomicronemia syndrome, such as eruptive
      xanthomas and lipemia retinalis, were not present and splenomegaly could not be
      documented due to a previous post-traumatic splenectomy. Based on clinical
      phenotype, an apolipoprotein C-II deficiency was excluded by a fresh plasma
      infusion test, in which clarification of the patient plasma was not obtained. The
      absence of changes in the lipoprotein electrophoretic plasma after heparin
      infusion can be secondary to a lipoprotein lipase deficiency, a rare genetic
      disorder with an incidence of one per million. In relation to the resistance to
      diet and drugs, plasma exchange therapy was performed. After 3 years of this
      treatment there was no significant progression of atherosclerosis.

PMID- 23871466
TI  - The blood supply in Sub-Saharan Africa: needs, challenges, and solutions.
AB  - Sub-Saharan Africa (SSA) is burdened with a growing population and poor health
      care resources. Transfusion medicine is uniquely affected for SSA as a result of
      a combination of factors which put tremendous pressure on the blood supply. In
      this review, we consider these factors including: malaria, sickle cell anemia,
      transfusion medicine infrastructure, and past transfusion medicine policies
      including those which are tied to foreign aid, such as a VNRD-only practice. We
      also consider how SSA can overcome some of these hurdles to achieve a safe and
      adequate blood supply for its people through the advent of new vaccines,
      medications, infrastructure development, policy changes, and education. 

PMID- 23871467
TI  - Preoperative decolonization effective at reducing staphylococcal colonization in
      total joint arthroplasty patients.
AB  - Staphylococcus decolonization prior to surgery is used to prevent surgical site
      infections (SSIs) after total joint arthroplasty (TJA). To determine if current
      treatment protocols result in successful decolonization of methicillin-sensitive
      S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA), 106 consecutive
      patients were screened for nasal MSSA/MRSA colonization pre-operatively and on
      the day of surgery. Colonized patients used intranasal mupirocin twice a day and
      chlorhexidine showers daily 5 days prior to surgery. Pre-operatively, 24 joints
      (22.0%) were positive for MSSA colonization and 5 joints (4.6%) were positive for
      MRSA colonization. On the day of surgery, 3 joints (2.8%) who underwent
      decolonization were positive for MSSA colonization and 0 joints were positive for
      MRSA colonization. The reduction in MSSA colonization was significant (P<0.001),
      while the eradication of MRSA colonization approached statistical significance
      (P=0.063). Current decolonization protocols using intranasal mupirocin and
      chlorhexidine washes are effective for reducing MRSA/MSSA colonization.

PMID- 23871468
TI  - Myositis ossificans of the temporalis muscle: case report and review of the
      literature.
AB  - Myositis ossificans, also known as traumatic myositis ossificans or myositis
      ossificans circumscripta, is the product of an unusual reactive process of
      mesenchymal stem cells within the muscle produced secondary to a traumatic insult
      or inflammatory process. In approximately 75% of cases, the process has a direct
      correlation with a single or repetitive, traumatic, penetrating, or crushing
      injury to the muscle. However, in up to 25% of cases, there is no recollection of
      a traumatic event. The most commonly accepted mechanism of traumatic etiology
      includes the embedment and lysis of bone fragments within the soft tissue causing
      subsequent exposure of bone morphogenic proteins to extraosseous cells. This
      environment stimulates osteoblasts to form true bone, dystrophic calcifications,
      or a calcified chondroid matrix. A concomitant mechanism that occurs involves the
      overproduction of bone morphogenic protein-4 produced by the muscle cells or the
      muscle fascia. 

PMID- 23871469
TI  - Choristoma involving the floor of the mouth and the anterior tongue: a case of
      teratoid cyst with gastric and respiratory epithelia.
AB  - Oral dysontogenic cysts result from defective embryonic development. Among them
      teratoid cysts are the most unusual presentation and may be lined by gastric,
      intestinal, respiratory, squamous, ciliated epithelium or even pancreatic
      structures. Teratoid cysts containing respiratory and gastrointestinal epithelium
      have typically been called choristomas. This article describes a 15-year-old boy
      presenting a choristoma involving both the floor of the mouth and the anterior
      tongue and characterized by the presence of squamous epithelium with skin adnexa,
      gastric and respiratory epithelium. 

PMID- 23871470
TI  - Common variants in CLOCK are not associated with measures of sleep duration in
      people of european ancestry from the sleep heart health study.

PMID- 23871471
TI  - Overexpression of corticotropin-releasing factor receptor type 2 in the bed
      nucleus of stria terminalis improves posttraumatic stress disorder-like symptoms
      in a model of incubation of fear.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a severe, persistent
      psychiatric disorder in response to a traumatic event, causing intense anxiety
      and fear. These responses may increase over time upon conditioning with fear
      associated cues, a phenomenon termed fear incubation. Corticotropin-releasing
      factor receptor type 1 (CRFR1) is involved in activation of the central stress
      response, while corticotropin-releasing factor receptor type 2 (CRFR2) has been
      suggested to mediate termination of this response. Corticotropin-releasing factor
      (CRF) receptors are found in stress-related regions, including the bed nucleus of
      stria terminalis (BNST), which is implicated in sustained fear. METHODS: Fear
      related behaviors were analyzed in rats exposed to predator-associated cues, a
      model of psychological trauma, over 10 weeks. Rats were classified as susceptible
      (PTSD-like) or resilient. Expression levels of CRF receptors were measured in the
      amygdala nuclei and BNST of the two groups. In addition, lentiviruses
      overexpressing CRFR2 were injected into the medial division, posterointermediate
      part of the BNST (BSTMPI) of susceptible and resilient rats and response to
      stress cues was measured. RESULTS: We found that exposure to stress and stress
      associated cues induced a progressive increase in fear response of susceptible
      rats. The behavioral manifestations of these rats were correlated both with
      sustained elevation in CRFR1 expression and long-term downregulation in CRFR2
      expression in the BSTMPI. Intra-BSTMPI injection of CRFR2 overexpressing
      lentiviruses attenuated behavioral impairments of susceptible rats. CONCLUSIONS:
      These results implicate the BNST CRF receptors in the mechanism of coping with
      stress. Our findings suggest increase of CRFR2 levels as a new approach for
      understanding stress-related atypical psychiatric syndromes such as PTSD.

PMID- 23871473
TI  - Mineralocorticoid receptor blockade prevents stress-induced modulation of
      multiple memory systems in the human brain.
AB  - BACKGROUND: Accumulating evidence suggests that stress may orchestrate the
      engagement of multiple memory systems in the brain. In particular, stress is
      thought to favor dorsal striatum-dependent procedural over hippocampus-dependent
      declarative memory. However, the neuroendocrine mechanisms underlying these
      modulatory effects of stress remain elusive, especially in humans. Here, we
      targeted the role of the mineralocorticoid receptor (MR) in the stress-induced
      modulation of dorsal striatal and hippocampal memory systems in the human brain
      using a combination of event-related functional magnetic resonance imaging and
      pharmacologic blockade of the MR. METHODS: Eighty healthy participants received
      the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor
      or control manipulation before they performed, in the scanner, a classification
      task that can be supported by the hippocampus and the dorsal striatum. RESULTS:
      Stress after placebo did not affect learning performance but reduced explicit
      task knowledge and led to a relative increase in the use of more procedural
      learning strategies. At the neural level, stress promoted striatum-based learning
      at the expense of hippocampus-based learning. Functional connectivity analyses
      showed that this shift was associated with altered coupling of the amygdala with
      the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before
      stress prevented the stress-induced shift toward dorsal striatal procedural
      learning, same as the stress-induced alterations of amygdala connectivity with
      hippocampus and dorsal striatum, but resulted in significantly impaired
      performance. CONCLUSIONS: Our findings indicate that the stress-induced shift
      from hippocampal to dorsal striatal memory systems is mediated by the amygdala,
      required to preserve performance after stress, and dependent on the MR.

PMID- 23871472
TI  - Reciprocal duplication of the Williams-Beuren syndrome deletion on chromosome
      7q11.23 is associated with schizophrenia.
AB  - BACKGROUND: Several copy number variants (CNVs) have been implicated as
      susceptibility factors for schizophrenia (SZ). Some of these same CNVs also
      increase risk for autism spectrum disorders, suggesting an etiologic overlap
      between these conditions. Recently, de novo duplications of a region on
      chromosome 7q11.23 were associated with autism spectrum disorders. The reciprocal
      deletion of this region causes Williams-Beuren syndrome. METHODS: We assayed an
      Ashkenazi Jewish cohort of 554 SZ cases and 1014 controls for genome-wide CNV. An
      excess of large rare and de novo CNVs were observed, including a 1.4 Mb
      duplication on chromosome 7q11.23 identified in two unrelated patients. To test
      whether this 7q11.23 duplication is also associated with SZ, we obtained data for
      14,387 SZ cases and 28,139 controls from seven additional studies with high
      resolution genome-wide CNV detection. We performed a meta-analysis, correcting
      for study population of origin, to assess whether the duplication is associated
      with SZ. RESULTS: We found duplications at 7q11.23 in 11 of 14,387 SZ cases with
      only 1 in 28,139 control subjects (unadjusted odds ratio 21.52, 95% confidence
      interval: 3.13-922.6, p value 5.5 * 10(-5); adjusted odds ratio 10.8, 95%
      confidence interval: 1.46-79.62, p value .007). Of three SZ duplication carriers
      with detailed retrospective data, all showed social anxiety and language delay
      premorbid to SZ onset, consistent with both human studies and animal models of
      the 7q11.23 duplication. CONCLUSIONS: We have identified a new CNV associated
      with SZ. Reciprocal duplication of the Williams-Beuren syndrome deletion at
      chromosome 7q11.23 confers an approximately tenfold increase in risk for SZ.

PMID- 23871475
TI  - A randomized trial of heart failure disease management in skilled nursing
      facilities: design and rationale.
AB  - BACKGROUND: Heart failure (HF) disease management can improve health outcomes for
      older community dwelling patients with heart failure. HF disease management has
      not been studied in skilled nursing facilities, a major site of transitional care
      for older adults. METHODS AND ANTICIPATED RESULTS: The objective of this trial is
      to investigate if a HF- disease management program (HF-DMP) in skilled nursing
      facilities (SNF)s will decrease all-cause rehospitalizations for the first 60
      days post-SNF admission. The trial is a randomized cluster trial to be conducted
      in 12 for-profit SNF in the greater Cleveland area. The study population is
      inclusive of patients with HF regardless of ejection fraction but excludes those
      patients on dialysis and with a life expectancy of 6 months or less. The HF-DMP
      includes 7 elements considered standard of care for patients with HF
      documentation of left ventricular function, tracking of weight and symptoms,
      medication titration, discharge instructions, 7-day follow-up appointment post
      SNF discharge, and patient education. The HF-DMP is conducted by a research nurse
      tasked with adhering to each element of the program and regularly audited to
      maintain fidelity of the program. Additional outcomes include health status, self
      care management, and discharge destination. CONCLUSIONS: The SNF-Connect Trial is
      the first trial of its kind to assess if a HF-DMP will improve outcomes for
      patients in SNFs. This trial will provide evidence on the effectiveness of HF-DMP
      to improve outcomes for older frail HF patients undergoing postacute
      rehabilitation.

PMID- 23871476
TI  - Oral lesion secondary to child abuse.

PMID- 23871477
TI  - Unicycle injuries in the United States.
AB  - BACKGROUND: Unicycles are single-wheel machines ridden for transportation or
      recreation. To our knowledge, no studies have been performed that describe injury
      rates of unicycle use. OBJECTIVE: The objective of this study was to describe the
      epidemiological characteristics of unicycle injuries treated in United States
      (US) emergency departments (EDs). METHODS: A retrospective analysis was performed
      using data from the National Electronic Injury Surveillance System (NEISS) of the
      US Consumer Product Safety Commission from 1991 through 2010. RESULTS: An
      estimated 3360 patients were treated for unicycle injuries from 1991 to 2010,
      averaging 168 injuries per year in the United States. Ten to fourteen-year-old
      patients represented 41% of the entire study cohort. Fractures represented
      approximately one third (32.9%) of all injuries treated. More than half (52.9%)
      of all injuries involved an extremity. Six of the 85 cases studied involved a
      head injury; all were aged younger than 18 years. Only 3.53% of all studied cases
      were admitted for further treatment. The rest were treated in the ED and
      discharged to home. Fractures were the primary diagnosis in all admitted cases.
      CONCLUSIONS: Based on NEISS data, unicycle injuries treated in EDs are relatively
      uncommon and rarely require admission. Of documented injuries, fractures and
      extremity injuries are most common. Additional research is needed to understand
      the underlying mechanisms of these injuries as well as the potential need for
      helmet use advocacy.

PMID- 23871478
TI  - Infantile botulism: a case report and review.
AB  - BACKGROUND: Infantile botulism is the result of ingestion of Clostridium
      botulinum spores, and is the most common form of infection with botulism in the
      United States. Ninety percent of cases occur in infants <6 months old. The
      infants typically present with vague symptoms such as hypotonia and poor feeding.
      This article reports an infant with confirmed infantile botulism that presented
      to the Emergency Department (ED) with complaints of decreased feeding and absence
      of bowel movements for >1 week. OBJECTIVES: Review a case of infantile botulism,
      its diagnosis, and treatment. CASE REPORT: A 4-month-old healthy Caucasian male
      presented to the ED with a 6-day history of decreased feeding after referral from
      the pediatrician. He had not had a bowel movement for 9 days, and his parents
      were also concerned about increasing weakness, as he was no longer able to hold
      his head up on his own. In the ED, he was minimally interactive. His vital signs
      were within normal limits, and he had hypoactive bowel sounds and decreased tone
      throughout. He was admitted to the Children's Hospital and eventually transferred
      to the Pediatric Intensive Care Unit requiring intubation and mechanical
      ventilation. The botulism immunoglobulin was administered, and a diagnosis was
      confirmed with positive botulinum toxin in the stool samples. Full recovery was
      made by the infant. CONCLUSION: Awareness of the symptoms of botulism and a high
      degree of clinical suspicion is needed to make a prompt diagnosis.

PMID- 23871479
TI  - Cardiotoxicity in a citalopram and olanzapine overdose.
AB  - BACKGROUND: This is a case of a citalopram and olanzapine overdose causing
      seizures and severe cardiotoxicity. CASE REPORT: A 21-year-old man presented
      unresponsive, with seizures, to an Emergency Department. The patient's initial
      electrocardiogram demonstrated a widened QRS of 160 ms and a normal QT/QTc
      interval of 400/487 ms consistent with cardiac sodium channel blockade. Within 30
      min of arrival, peak citalopram and olanzapine levels were measured to be 522
      ng/mL and 505 ng/mL, respectively. Measured levels remained supratherapeutic
      until 13.6 h and 42.6 h after arrival for citalopram and olanzapine,
      respectively. The patient developed bradycardia and hypotension that required
      multimodal therapies including sodium bicarbonate boluses, vasopressors, and
      transvenous pacing. Seizures and cardiotoxicity continued while citalopram, but
      not olanzapine, was supratherapeutic. CONCLUSIONS: This case describes
      cardiotoxicity directly correlated with supratherapeutic citalopram levels in
      overdose.

PMID- 23871480
TI  - Sports medicine training and practice opportunities for emergency physicians.
AB  - BACKGROUND: There is growing interest among emergency physicians to seek
      additional training in Sports Medicine (SM) and to add it to their clinical
      practice. This presents unique training and practice management issues. The
      majority of Primary Care SM fellowship programs list that they will accept
      emergency physicians, and approximately one-third have already had an emergency
      physician as an SM fellow. OBJECTIVES: The objective of this article is to
      provide an overview of the key elements for emergency physicians to consider as
      they pursue SM career goals. DISCUSSION: Training needs such as continuity of
      care as it pertains to the athlete, SM skills development, and practice
      management are reviewed. Practice challenges such as malpractice insurance and
      billing issues are discussed. Examples of several practice models are presented.
      Evolving trends in SM practice and training opportunities for emergency
      physicians are discussed as well. CONCLUSIONS: Sports Medicine is a viable career
      option for emergency physicians and may complement their skills set in the
      management of acute injuries. Practice and training opportunities will continue
      to evolve as this pathway into the practice of SM gains further recognition.

PMID- 23871481
TI  - Renal artery mycotic aneurysm in a drug abuser.

PMID- 23871474
TI  - A genome-wide association analysis of a broad psychosis phenotype identifies
      three loci for further investigation.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified several loci
      associated with schizophrenia and/or bipolar disorder. We performed a GWAS of
      psychosis as a broad syndrome rather than within specific diagnostic categories.
      METHODS: 1239 cases with schizophrenia, schizoaffective disorder, or psychotic
      bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls
      were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP)
      array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines
      information across families and unrelated individuals. We attempted to replicate
      signals found in 23 genomic regions using existing data on nonoverlapping samples
      from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352
      schizophrenia patients and 24,474 controls). RESULTS: No individual SNP showed
      compelling evidence for association with psychosis in our data. However, we
      observed a trend for association with same risk alleles at loci previously
      associated with schizophrenia (one-sided p = .003). A polygenic score analysis
      found that the Psychiatric GWAS Consortium's panel of SNPs associated with
      schizophrenia significantly predicted disease status in our sample (p = 5 * 10(
      14)) and explained approximately 2% of the phenotypic variance. CONCLUSIONS:
      Although narrowly defined phenotypes have their advantages, we believe new loci
      may also be discovered through meta-analysis across broad phenotypes. The novel
      statistical methodology we introduced to model effect size heterogeneity between
      studies should help future GWAS that combine association evidence from related
      phenotypes. Applying these approaches, we highlight three loci that warrant
      further investigation. We found that SNPs conveying risk for schizophrenia are
      also predictive of disease status in our data.

PMID- 23871482
TI  - Elevated compartment pressures from copperhead envenomation successfully treated
      with antivenin.
AB  - BACKGROUND: Copperhead envenomation causes local soft tissue effects; however,
      associated compartment syndrome is rare. We report a case of a 17-month-old with
      significantly elevated compartment pressures successfully treated with antivenin
      and supportive care. CASE REPORT: A 17-month-old girl sustained a copperhead bite
      to the foot and presented with circumferential edema, erythema, and ecchymosis of
      the foot and distal ankle. The patient had palpable pulses and was neurologically
      intact. Four vials of Crotalidae polyvalent immune Fab was initiated and
      additional doses were administered in an attempt to achieve local control. Within
      10 h of presentation, the patient's edema extended to the groin, although
      sensation was maintained and pulses were documented by Doppler. Lower-extremity
      compartment pressures were measured and were most notable for an anterior
      pressure of 85 mm Hg, despite having received 12 vials of antivenin. Fasciotomy
      was deferred and the patient received two additional six-vial doses of antivenin
      to achieve local control. Compartment pressures improved with a 2.2-cm mean
      decrease in limb diameter within 48 h. Maintenance dosing was initiated and the
      patient ultimately received a total of 26 vials of antivenin. The patient did not
      develop significant coagulopathy or thrombocytopenia. Swelling continued to
      improve with return of limb function. CONCLUSION: In this case, early and
      aggressive treatment with antivenin may have avoided invasive fasciotomy, and its
      use should be considered in patients with copperhead envenomation and
      significantly elevated compartment pressures.

PMID- 23871483
TI  - Sacrococcygeal foreign body progressing with pilonidal sinus clinical picture:
      report of a case.
AB  - BACKGROUND: Pilonidal sinus is a benign anorectal disease that is frequently seen
      in the sacrococcygeal area when a foreign body reaction develops after the
      invasion of hair follicles. OBJECTIVES: Trauma in this region and clinical
      abscesses that recur after trauma due to foreign bodies are not frequently
      observed. CASE REPORT: This study presents the case of a patient with chronic
      leakage who had a history of three surgical procedures due to recurrent pilonidal
      abscesses and the presence of a foreign body in the sacrococcygeal area.
      CONCLUSION: The presence of a foreign body in cases progressing with a single and
      wide inlet and frequently recurring abscess formation is a condition of which to
      be aware.

PMID- 23871484
TI  - The cardiac ryanodine receptor N-terminal region contains an anion binding site
      that is targeted by disease mutations.
AB  - Ryanodine receptors (RyRs) are calcium release channels located in the membrane
      of the endoplasmic and sarcoplasmic reticulum and play a major role in muscle
      excitation-contraction coupling. The cardiac isoform (RyR2) is the target for
      >150 mutations that cause catecholaminergic polymorphic ventricular tachycardia
      (CPVT) and other conditions. Here, we present the crystal structure of the N
      terminal region of RyR2 (1-547), an area encompassing 29 distinct disease
      mutations. The protein folds up in three individual domains, which are held
      together via a central chloride anion that shields repulsive positive charges.
      Several disease mutant versions of the construct drastically destabilize the
      protein. The R420Q disease mutant causes CPVT and ablates chloride binding. The
      mutation results in reorientations of the first two domains relative to the third
      domain. These conformational changes likely activate the channel by destabilizing
      intersubunit interactions that are disrupted upon channel opening. 

PMID- 23871485
TI  - Assembly-directed antivirals differentially bind quasiequivalent pockets to
      modify hepatitis B virus capsid tertiary and quaternary structure.
AB  - Hepatitis B virus (HBV) is a major cause of liver disease. Assembly of the HBV
      capsid is a critical step in virus production and an attractive target for new
      antiviral therapies. We determined the structure of HBV capsid in complex with AT
      130, a member of the phenylpropenamide family of assembly effectors. AT-130
      causes tertiary and quaternary structural changes but does not disrupt capsid
      structure. AT-130 binds a hydrophobic pocket that also accommodates the
      previously characterized heteroaryldihydropyrimidine compounds but favors a
      unique quasiequivalent location on the capsid surface. Thus, this pocket is a
      promiscuous drug-binding site and a likely target for different assembly
      effectors with a broad range of mechanisms of activity. That AT-130 successfully
      decreases virus production by increasing capsid assembly rate without disrupting
      capsid structure delineates a paradigm in antiviral design, that disrupting
      reaction timing is a viable strategy for assembly effectors of HBV and other
      viruses. 

PMID- 23871486
TI  - Competition of cell adhesion and immune recognition: insights into the
      interaction between CRTAM and nectin-like 2.
AB  - Nectin and nectin-like proteins are cell adhesion molecules that mediate the
      formation of cell adherens junctions by forming homo- or heterodimers. Some
      members of this protein family can also be used by immune receptors to mediate
      immune recognition. For instance, nectin-like 2 (Necl-2) is used as a ligand for
      the immune system by interaction with the immune receptor CRTAM (class-I MHC
      restricted T cell associated molecule), which is mainly expressed on the surface
      of cytotoxic lymphocyte cells. However, the Necl-2/CRTAM binding mode and its
      relationship to cell adhesion are not known. Here, we report a Necl-2/CRTAM
      complex structure, demonstrating that Necl-2 binding to CRTAM competes with the
      dimerization of CRTAM and possibly Necl-2. Necl-2 occupies the CRTAM homodimer
      interface, making homodimerization impossible. Mutational and functional analyses
      identified key amino acids (double "lock-and-key") responsible for the binding.
      Our work illustrates how the cell adhesion molecule Necl-2 competitively binds
      the immune receptor CRTAM. 

PMID- 23871488
TI  - The antioxidant idebenone fails to prevent or attenuate chronic experimental
      autoimmune encephalomyelitis in the mouse.
AB  - Oxidative stress and mitochondrial dysfunction appear to contribute to
      neurodegenerative processes during multiple sclerosis (MS). Thus, antioxidants
      may represent a therapeutic option for MS. The antioxidant idebenone was proven
      to be beneficial in Friedreich's ataxia and Leber's hereditary optic neuropathy,
      two disorders caused by mitochondrial alterations. Here we showed that idebenone
      protected neuronal HT22 cells from glutamate-induced death in vitro. However, in
      experimental autoimmune encephalomyelitis, idebenone failed to affect disease
      incidence or onset when applied preventively, or to reduce disease severity when
      applied therapeutically. Histopathological examination of CNS from idebenone
      treated mice showed no improvement in inflammation, demyelination, or axonal
      damage. Thus, we hypothesize that idebenone treatment will likely not benefit
      patients with MS.

PMID- 23871487
TI  - Tolerance has its limits: how the thymus copes with infection.
AB  - The thymus is required for T cell differentiation; a process that depends on
      which antigens are encountered by thymocytes, the environment surrounding the
      differentiating cells, and the thymic architecture. These features are altered by
      local infection of the thymus and by the inflammatory mediators that accompany
      systemic infection. Although once believed to be an immune privileged site, it is
      now known that antimicrobial responses are recruited to the thymus. Resolving
      infection in the thymus is important because chronic persistence of microbes
      impairs the differentiation of pathogen-specific T cells and diminishes
      resistance to infection. Understanding how these mechanisms contribute to disease
      susceptibility, particularly in infants with developing T cell repertoires,
      requires further investigation. 

PMID- 23871489
TI  - Frequent inaccuracies in ABCD2 scoring in non-stroke specialists' referrals to a
      daily Rapid Access Stroke Prevention service.
AB  - The 'accuracy' of age, blood pressure, clinical features, duration and diabetes
      (ABCD(2)) scoring by non-stroke specialists referring patients to a daily Rapid
      Access Stroke Prevention (RASP) service is unclear, as is the accuracy of ABCD(2)
      scoring by trainee residents. In this prospective study, referrals were
      classified as 'confirmed TIAs' if the stroke specialist confirmed a clinical
      diagnosis of possible, probable or definite TIA, and 'non-TIAs' if patients had a
      TIA mimic or completed stroke. ABCD(2) scores from referring physicians were
      compared with scores by experienced stroke specialists and neurology/geriatric
      medicine residents at a daily RASP clinic; inter-observer agreement was examined.
      Data from 101 referrals were analysed (mean age=60.0years, 58% male). The median
      interval between referral and clinic assessment was 1day. Of 101 referrals, 52
      (52%) were 'non-TIAs': 45 (86%) of 52 were 'TIA mimics' and 7 (14%) of 52 were
      completed strokes. There was only 'fair' agreement in total ABCD(2) scoring
      between referring physicians and stroke specialists (kappa=0.37). Agreement was
      'excellent' between residents and stroke specialists (kappa=0.91). Twenty of 29
      patients scored as 'moderate to high risk' (score 4-6) by stroke specialists were
      scored 'low risk' (score 0-3) by referring physicians. ABCD(2) scoring by
      referring doctors is frequently inaccurate, with a tendency to underestimate
      stroke risk. These findings emphasise the importance of urgent specialist
      assessment of suspected TIA patients, and that ABCD(2) scores by non-stroke
      specialists cannot be relied upon in isolation to risk-stratify patients. Inter
      observer agreement in ABCD(2) scoring was 'excellent' between residents and
      stroke specialists, indicating short-term training may improve accuracy. 

PMID- 23871490
TI  - 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer
      (HERA): an open-label, randomised controlled trial.
AB  - BACKGROUND: Trastuzumab has established efficacy against breast cancer with
      overexpression or amplification of the HER2 oncogene. The standard of care is 1
      year of adjuvant trastuzumab, but the optimum duration of treatment is unknown.
      We compared 2 years of treatment with trastuzumab with 1 year of treatment, and
      updated the comparison of 1 year of trastuzumab versus observation at a median
      follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA)
      trial. METHODS: The HERA trial is an international, multicentre, randomised, open
      label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with
      observation after standard neoadjuvant chemotherapy, adjuvant chemotherapy, or
      both in 5102 patients with HER2-positive early breast cancer. The primary
      endpoint was disease-free survival. The comparison of 2 years versus 1 year of
      trastuzumab treatment involved a landmark analysis of 3105 patients who were
      disease-free 12 months after randomisation to one of the trastuzumab groups, and
      was planned after observing at least 725 disease-free survival events. The
      updated intention-to-treat comparison of 1 year trastuzumab treatment versus
      observation alone in 3399 patients at a median follow-up of 8 years (range 0-10)
      is also reported. This study is registered with ClinicalTrials.gov, number
      NCT00045032. FINDINGS: We recorded 367 events of disease-free survival in 1552
      patients in the 1 year group and 367 events in 1553 patients in the 2 year group
      (hazard ratio [HR] 0.99, 95% CI 0.85-1.14, p=0.86). Grade 3-4 adverse events and
      decreases in left ventricular ejection fraction during treatment were reported
      more frequently in the 2 year treatment group than in the 1 year group (342
      [20.4%] vs 275 [16.3%] grade 3-4 adverse events, and 120 [7.2%] vs 69 [4.1%]
      decreases in left ventricular ejection fraction, respectively). HRs for a
      comparison of 1 year of trastuzumab treatment versus observation were 0.76 (95%
      CI 0.67-0.86, p<0.0001) for disease-free survival and 0.76 (0.65-0.88, p=0.0005)
      for overall survival, despite crossover of 884 (52%) patients from the
      observation group to trastuzumab therapy. INTERPRETATION: 2 years of adjuvant
      trastuzumab is not more effective than is 1 year of treatment for patients with
      HER2-positive early breast cancer. 1 year of treatment provides a significant
      disease-free and overall survival benefit compared with observation and remains
      the standard of care. FUNDING: F Hoffmann-La Roche (Roche).

PMID- 23871491
TI  - Good news on dementia prevalence--we can make a difference.

PMID- 23871493
TI  - Duration of adjuvant trastuzumab: shorter beats longer.

PMID- 23871494
TI  - The relationship of family characteristics and bipolar disorder using causal-pie
      models.
AB  - Many family characteristics were reported to increase the risk of bipolar
      disorder (BPD). The development of BPD may be mediated through different
      pathways, involving diverse risk factor profiles. We evaluated the associations
      of family characteristics to build influential causal-pie models to estimate
      their contributions on the risk of developing BPD at the population level. We
      recruited 329 clinically diagnosed BPD patients and 202 healthy controls to
      collect information in parental psychopathology, parent-child relationship, and
      conflict within family. Other than logistic regression models, we applied causal
      pie models to identify pathways involved with different family factors for BPD.
      The risk of BPD was significantly increased with parental depression, neurosis,
      anxiety, paternal substance use problems, and poor relationship with parents.
      Having a depressed mother further predicted early onset of BPD. Additionally, a
      greater risk for BPD was observed with higher numbers of paternal/maternal
      psychopathologies. Three significant risk profiles were identified for BPD,
      including paternal substance use problems (73.0%), maternal depression (17.6%),
      and through poor relationship with parents and conflict within the family (6.3%).
      Our findings demonstrate that different aspects of family characteristics elicit
      negative impacts on bipolar illness, which can be utilized to target specific
      factors to design and employ efficient intervention programs. 

PMID- 23871492
TI  - A two-decade comparison of prevalence of dementia in individuals aged 65 years
      and older from three geographical areas of England: results of the Cognitive
      Function and Ageing Study I and II.
AB  - BACKGROUND: The prevalence of dementia is of interest worldwide. Contemporary
      estimates are needed to plan for future care provision, but much evidence is
      decades old. We aimed to investigate whether the prevalence of dementia had
      changed in the past two decades by repeating the same approach and diagnostic
      methods as used in the Medical Research Council Cognitive Function and Ageing
      Study (MRC CFAS) in three of the original study areas in England. METHODS:
      Between 1989 and 1994, MRC CFAS investigators did baseline interviews in
      populations aged 65 years and older in six geographically defined areas in
      England and Wales. A two stage process, with screening followed by diagnostic
      assessment, was used to obtain data for algorithmic diagnoses (geriatric mental
      state-automated geriatric examination for computer assisted taxonomy), which were
      then used to estimate dementia prevalence. Data from three of these areas-
      Cambridgeshire, Newcastle, and Nottingham--were selected for CFAS I. Between 2008
      and 2011, new fieldwork was done in the same three areas for the CFAS II study.
      For both CFAS I and II, each area needed to include 2500 individuals aged 65
      years and older to provide power for geographical and generational comparison.
      Sampling was stratified according to age group (65-74 years vs >=75 years). CFAS
      II used identical sampling, approach, and diagnostic methods to CFAS I, except
      that screening and assessement were combined into one stage. Prevalence estimates
      were calculated using inverse probability weighting methods to adjust for
      sampling design and non-response. Full likelihood Bayesian models were used to
      investigate informative non-response. FINDINGS: 7635 people aged 65 years or
      older were interviewed in CFAS I (9602 approached, 80% response) in
      Cambridgeshire, Newcastle, and Nottingham, with 1457 being diagnostically
      assessed. In the same geographical areas, the CFAS II investigators interviewed
      7796 individuals (14,242 approached, 242 with limited frailty information, 56%
      response). Using CFAS I age and sex specific estimates of prevalence in
      individuals aged 65 years or older, standardised to the 2011 population, 8.3%
      (884,000) of this population would be expected to have dementia in 2011. However,
      CFAS II shows that the prevalence is lower (6.5%; 670,000), a decrease of 1.8%
      (odds ratio for CFAS II vs CFAS I 0.7, 95% CI 0.6-0.9, p=0.003). Sensitivity
      analyses suggest that these estimates are robust to the change in response.
      INTERPRETATION: This study provides further evidence that a cohort effect exists
      in dementia prevalence. Later-born populations have a lower risk of prevalent
      dementia than those born earlier in the past century. FUNDING: UK Medical
      Research Council.

PMID- 23871495
TI  - Gene suppression via U1 small nuclear RNA interference (U1i) machinery using
      oligonucleotides containing 2'-modified-4'-thionucleosides.
AB  - Gene suppression via U1 small nuclear RNA interference (U1i) is considered to be
      one of the most attractive approaches, and takes the place of general antisense,
      RNA interference (RNAi), and anti-micro RNA machineries. Since the U1i can be
      induced by short oligonucleotides (ONs), namely U1 adaptors consisting of a
      'target domain' and a 'U1 domain', we prepared adaptor ONs using 2'-modified-4'
      thionucleosides developed by our group, and evaluated their U1i activity. As a
      result, the desired gene suppression via U1i was observed in ONs prepared as a
      combination of 2'-fluoro-4'-thionucleoside and 2'-fluoronucleoside units as well
      as only 2'-fluoronucleoside units, while those prepared as combination of 2'-OMe
      nucleoside/2'-OMe-4'-thionucleoside and 2'-fluoronucleoside units did not show
      significant activity. Measurement of Tm values indicated that a higher
      hybridization ability of adaptor ONs with complementary RNA is one of the
      important factors to show potent U1i activity. 

PMID- 23871496
TI  - Body adiposity but not insulin resistance is associated with -675 4G/5G
      polymorphism in the PAI-1 gene in a sample of Mexican children.
AB  - OBJECTIVE: To assess whether the -675 4G/5G polymorphism in the plasminogen
      activator inhibitor-1 gene is associated with obesity and insulin resistance in
      Mexican children. METHODS: A cross-sectional study was performed in 174 children,
      89 with normal-weight and 85 with obesity, aged from 6 to 13 years. All children
      were from state of Guerrero, and recruited from three primary schools in the city
      of Chilpancingo, state of Guerrero, Mexico. Insulin levels were determined by
      immunoenzymatic assay. The homeostasis model assessment was used to determine
      insulin resistance. The -675 4G/5G polymorphism in PAI-1 gene was analyzed by
      polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The
      prevalence of insulin resistance in the obese group was higher (49.41%) than in
      the normal-weight group (16.85%). The 4G/5G PAI-1 polymorphism was found in Hardy
      Weinberg equilibrium. The 4G/5G genotype contributed to a significant increase in
      waist-hip ratio (beta=0.02, p=0.006), waist circumference (beta=4.42, p=0.009),
      and subscapular skinfold thickness (beta=1.79, p=0.04); however, it was not
      related with insulin resistance. CONCLUSION: The -675 4G/5G genotype of PAI-1
      gene was associated with increase of body adiposity in Mexican children.

PMID- 23871497
TI  - Respiratory viral coinfection and clinical disease severity.

PMID- 23871498
TI  - Degree of compliance with the ten steps of the Breastfeeding Friendly Primary
      Care Initiative and its association with the prevalence of exclusive
      breastfeeding.
AB  - OBJECTIVE: To analyze the association between the degree of compliance with the
      ten steps of the Breastfeeding-Friendly Primary Care Initiative (BFPCI) and the
      prevalence of exclusive breastfeeding (EBF) in infants younger than six months in
      the city of Rio de Janeiro. METHODS: This was a cross-sectional study conducted
      in a representative sample of 56 primary health care units of this municipality.
      The assessment of compliance with the ten steps of the BFPCI was carried out by
      interviewing health care professionals, pregnant women, and mothers; the
      generated performance scores were classified into tertiles. To obtain the
      outcome, i.e., the EBF, a data collection questionnaire was applied to mothers of
      children younger than six months who were followed up at these units in November
      of 2007. Prevalence ratios were obtained for the EBF using Poisson regression
      with robust variance. RESULTS: The prevalence of EBF was 47.6%. In the
      multivariate analysis, the upper tertile of performance showed a 34% higher
      prevalence of EBF (PR=1.34, 95% CI: 1.24 to 1.44) and the second tertile was 17%
      higher (PR=1.17, 95% CI: 1.08 to 1.27) than the first tertile. Mothers who did
      not work outside home had a 75% higher prevalence of EBF (PR=1.75, 95% CI: 1.53
      to 2.01); assistance in a basic health unit, as opposed to a family health unit,
      implied a 10% higher prevalence (PR=1.10, 95% CI: 1.03 to 1.19). The prevalence
      of EBF decreased 1% for each day of the infant's life (PR=0.993, 95% CI: 0.992 to
      0.993). CONCLUSION: Given the contribution of BFPCI to the practice of EBF, a
      greater investment in the expansion and sustainability of this initiative is
      recommended, as well as its association with other strategies to promote,
      protect, and support breastfeeding.

PMID- 23871499
TI  - Rotavirus epidemiology before and after vaccine introduction.
AB  - OBJECTIVES: To evaluate the prevalence and circulation of rotavirus genotypes
      before and after the introduction of oral vaccine against human rotavirus, and to
      check for a possible change in the age of occurence of the infection by RV-A.
      METHODS: This was a cross-sectional study conducted between 2002-2011, in the
      city of Juiz de Fora, state of Minas Gerais, Brazil. A total of 1,144 diarrheal
      stool specimens were obtained from nonhospitalized children aged between 0 and 5
      years, and analyzed by polyacrylamide gel electrophoresis and reverse
      transcription polymerase chain reaction for genotype characterization. Data on
      prevalence and age distribution of rotavirus cases were analyzed through the chi
      squared test (p < 0.05), using SPSS, release 13.0. RESULTS: Rotavirus infection
      was detected in 9.35% (107/1,144) samples, with prevalence rates ranging from
      11.12% (90/809) in the pre-vaccine to 5.07% (17/335) in the post-vaccine period
      (p = 0.001). Among the samples tested, the most frequently detected genotypes
      were G1P[6] (6/33 = 18.2%) in the period between 2002 and 2005 and G2P[4] in 2006
      (11/33 = 33.3%) and in the period between 2007 and 2011 (5/33 = 15.2%). There was
      also a significant reduction in the number of cases of rotavirus disease in
      children aged between 0 and 36 months after the vaccine introduction.
      CONCLUSIONS: The study evidenced a significant decrease in the prevalence of
      rotavirus, mainly in children aged between 0 and 36 months in the 2007-2011
      period, as well as a reduction in G1 genotype circulation.

PMID- 23871500
TI  - Impact of elective hospital admissions on glycaemic control in adolescents with
      poorly controlled type 1 diabetes.
AB  - AIM: Different treatment strategies have been used to manage adolescents with
      poorly controlled type 1 diabetes. We investigated whether a brief elective
      hospital admission improves haemoglobin A(1c) (HbA(1c)) over 12 months. METHODS:
      We studied a retrospective cohort of adolescents with poorly controlled type 1
      diabetes attending a tertiary care pediatric diabetes clinic in Montreal, Canada,
      between January 2005 and December 2010. Hospitalized adolescents (admitted group)
      were matched with controls (non-admitted group) for age and baseline HbA(1c).
      HbA(1c) values at baseline, 6 and 12 months were obtained from the clinic
      database. RESULTS: Thirty patients aged 11 to 17 years with a first elective
      admission for poor metabolic control were paired with 30 non-admitted patients.
      At baseline, HbA(1c) was 12.2+/-1.6% in admitted and 12.0+/-1.2% in non-admitted
      patients. There were no clinically important differences in potential confounders
      between groups. There was no improvement in the primary outcome as assessed by
      the change in HbA(1c) at 12 months in the admitted group (-1.3+/-2.3%) compared
      with the non-admitted group (-2.1+/-1.7%) (P=0.078). No improvement in
      intermediary measures of glycaemic control was observed (HbA(1c) at 6 months or
      change at 6 months). After 12 months, HbA(1c) values were higher in the admitted
      group (10.9+/-1.9%) versus the non-admitted group (9.9+/-1.4%) (P=0.016).
      CONCLUSION: Elective hospital admission for adolescents with poorly controlled
      type 1 diabetes does not seem to be an effective strategy to improve HbA(1c) over
      12 months.

PMID- 23871501
TI  - Lack of replication of common EXT2 gene variants with susceptibility to type 2
      diabetes in Lebanese Arabs.
AB  - OBJECTIVE: Recent genome-wide association studies and replication analyses have
      reported the association of variants of the exostosin-2 (EXT2) gene and risk of
      type 2 diabetes mellitus (T2DM) in some populations, but not in others. This
      study investigated the associations of EXT2 variants rs1113132, rs3740878 and
      rs11037909 with T2DM in a Lebanese Arab population. METHODS: This case-control
      study involved 995 T2DM patients and 1076 control subjects. Genotyping was done
      by the allelic exclusion method. RESULTS: While minor allele frequencies (MAFs)
      of rs11037909 (P=0.028) and rs3740878 (P=0.048), but not rs1113132 (P=0.841),
      were higher in patients, this was lost after correcting for multiple testing.
      Apart from EXT2 rs1113132, which was marginally associated with T2DM in the
      additive model (P=0.054), but not after adjustment for covariates, none of the
      tested EXT2 SNPs were associated with T2DM in any of the genetic models tested.
      However, variable associations of EXT2 variants with T2DM were noted according to
      BMI status. While the three tested EXT2 variants were not associated with T2DM in
      obese subjects, rs1113132 and rs11037909, but not rs3740878, were associated with
      T2DM in non-obese subjects. Meta-analysis revealed a significant association of
      rs11037909 and a marginal association of rs3740878 with T2DM in the fixed model.
      Using a common (GTA) haplotype as reference, three-locus
      (rs1113132/rs11037909/rs3740878) haplotype analysis demonstrated no association
      between any of the EXT2 haplotypes with T2DM, not even before correcting for
      multiple testing. CONCLUSION: This study demonstrated no association of
      rs1113132, rs3740878 and rs11037909 EXT2 variants with T2DM.

PMID- 23871502
TI  - Changes in body mass index following newly diagnosed type 2 diabetes and risk of
      cardiovascular mortality: a cohort study of 8486 primary-care patients.
AB  - AIMS: Elevated body mass index (BMI) is associated with an increased risk of type
      2 diabetes and cardiovascular disease (CVD). This study explored the association
      between BMI changes in the first 18 months of newly diagnosed type 2 diabetes and
      the risk of long-term CVD mortality. METHODS: A total of 8486 patients with newly
      diagnosed type 2 diabetes and no previous history of CVD or cancer were
      identified from 84 primary-care centres in Sweden. During the first year after
      diagnosis, patients were grouped according to BMI change: 'Increase', or >=+1 BMI
      unit; 'unchanged', or between +1 and-1 BMI unit; and 'decrease', or <=-1 BMI
      unit. Associations between BMI change and CVD mortality, defined as death from
      stroke, myocardial infarction or sudden death, were estimated using adjusted Cox
      proportional hazards models (NCT 01121315). RESULTS: Baseline mean age was 60.0
      years and mean BMI was 30.2kg/m(2). Patients were followed for up to 9 years
      (median: 4.6 years). During the first 18 months, 53.4% had no change in their
      BMI, while 32.2% decreased and 14.4% increased. Compared with patients with
      unchanged BMI, those with an increased BMI had higher risks of CVD mortality
      (hazard ratio: 1.63, 95% CI: 1.11-2.39) and all-cause mortality (1.33, 1.01
      1.76). BMI decreases had no association with these risks compared with unchanged
      BMI: 1.06 (0.76-1.48) and 1.06 (0.85-1.33), respectively. CONCLUSION: Increased
      BMI within the first 18 months of type 2 diabetes diagnosis was associated with
      an increased long-term risk of CVD mortality. However, BMI decrease did not lower
      the long-term risk of mortality.

PMID- 23871503
TI  - Re metformin revisited: a critical review of the benefit-risk balance in at-risk
      patients with type 2 diabetes.

PMID- 23871504
TI  - Measuring safety culture in Palestinian neonatal intensive care units using the
      Safety Attitudes Questionnaire.
AB  - PURPOSE: This study aimed to measure safety culture, examine variations among
      neonatal intensive care units (NICUs), and assess the associations with caregiver
      characteristics. MATERIALS AND METHODS: A cross-sectional design was used,
      utilizing the Arabic version of the Safety Attitudes Questionnaire, administered
      to all 305 nurses and physicians working in the 16 NICUs in the West Bank.
      RESULTS: There were 204 participants, comprising of mainly nurses (80.4%), women
      (63%), 30 years or younger (62.6%), holding a bachelor's degree or more (66.7%),
      and with at least 5 years of experience in the profession (60.3%). Safety
      Attitudes Questionnaire mean domain scores ranged from 71.22 for job satisfaction
      to 63 for stress recognition on a 100-point scale; the scores varied
      significantly among NICUs (P<.05). About 85% of the participants rated the safety
      grade either excellent or very good; 71.0% did not report any event in the past
      year. CONCLUSIONS: We found large variations in safety culture within and between
      a comprehensive sample of Palestinian NICUs. The findings suggest the need for a
      customized approach that builds on existing strengths and targets areas of
      opportunities for improvement to optimize health care delivery to the most
      vulnerable of patients, sick newborns in the NICU setting.

PMID- 23871505
TI  - Perceptions, attitudes and experiences of family caregivers of patients with
      musculoskeletal diseases: a qualitative approach.
AB  - OBJECTIVE: To determine the perceptions, attitudes and experiences among family
      caregivers of patients with musculoskeletal diseases (MSD). METHODS: Descriptive,
      exploratory, qualitative study. Two discussion groups were organized with family
      caregivers of MSD patients, representing the caregiver profile: gender
      (men/women) and age (31-45 years/46-65 years); and patient profiles: MSD type
      (rheumatoid arthritis/ankylosing spondylitis), work status (yes or no for the
      variables housewife, at least 3 episodes of sick leave, patients who abandoned
      their work, and patients with permanent work disability). A content analysis
      based on the Grounded Theory was done to detect and explore emerging categories.
      RESULTS: The emerging dimensions were: alterations in daily life activities, need
      for caregiver support, physical and psychological impact on the caregiver,
      characteristics of the patient, and several aspects of care. Relevant experiences
      mentioned were: the diagnosis of a MSD changes the patient and their family
      members' life affecting work, financial, social, psychological and physical
      spheres, making it necessary help for basic activities of daily living. Early age
      at onset or severe MSDs require dedication and effort on the part of caregivers
      which increases with time. This leads to a great emotional overload on the
      caregivers, which may be modulated by the support they receive when providing
      care. CONCLUSION: The primary consequences for caregivers are loss of purchasing
      power, work problems, social isolation and emotional stress. Programs for
      effective at-home support need to be developed with streamlined administrative
      processes to quickly classify the level of disability and provide official
      assistance.

PMID- 23871506
TI  - Craniofacial fibrous dysplasia surgery: a functional approach.
AB  - BACKGROUND: Craniofacial fibrous dysplasia has not only esthetic but functional
      impact. Surgery is controversial, ranging from conservative to radical. It
      involves elevated hemorrhage risk, and should be progressive, based on an
      individual risk/benefit analysis with the aim of improving quality of life. CASE
      REPORTS: Three patients (one male, two female; mean age, 35 years) with evolutive
      orbital-temporal maxillary dysplasia were treated between 2008 and 2009 in our
      department. All showed exophthalmia and nasal obstruction. In one patient,
      symptomatology was aggravated by a frontal sinus cyst within the dysplasia.
      Another had associated auditory canal obstruction inducing recurrent external
      otitis. Optic nerve decompression was achieved on a combined coronal and
      endonasal approach, assisted by neuronavigation. Complementary remodelling
      resection, dacryocystorhinostomy and internal optic nerve decompression were
      performed. Functional results showed 70 % improvement on a subjective scale for
      eye tension and nasal obstruction. Surgery was feasible in all patients, with no
      complications. CONCLUSION: Current surgical management allies esthetic and
      functional concerns. Remodeling resection is the reference technique. The coronal
      approach is a good primary option for optic nerve decompression. Endonasal
      surgery with neuronavigation improves nasal ventilation and lacrimal canal
      permeability.

PMID- 23871507
TI  - Feasibility of audit methods to study access to substance use treatment.
AB  - Audit studies represent an emerging method for examining disparities in access to
      care, like substance use treatment, whereby fake patients (i.e., actors) attempt
      to procure a service with one or more characteristics isolated across condition.
      This allows for manipulation of variables, like insurance status, that are
      normally fixed or impossible to standardize with precision when studying actual
      patients. This pilot study explored whether these methods were feasible for the
      examination of community-based substance use treatment access. Masked telephone
      calls (n=48) were made to providers (k=8) in a single city seeking an
      appointment. A male and female "patient" made calls in three insurance status
      conditions: no insurance, state-funded insurance, and private insurance. All
      other subject characteristics were held constant. Results showed an audit design
      to be a feasible method for examining disparities in access and demonstrated
      substantial barriers to voluntary treatment. Implications and future directions
      are discussed. 

PMID- 23871509
TI  - Impact of attenuated plaque as detected by intravascular ultrasound on the
      occurrence of microvascular obstruction after percutaneous coronary intervention
      in patients with ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: The aim of the study was to investigate whether intravascular
      ultrasound (IVUS) can predict microvascular obstruction (MVO) as detected by
      magnetic resonance imaging (MRI) after primary percutaneous coronary intervention
      (PCI) in patients with ST-segment elevation myocardial infarction (STEMI).
      BACKGROUND: MVO occurs in a sizable proportion of patients with acute myocardial
      infarction despite successful PCI and results in poor clinical outcomes. METHODS:
      We assessed infarct-related lesions in 68 patients with STEMI by using IVUS
      before primary PCI. All patients were examined by MRI 1 week after primary PCI.
      RESULTS: MRI-derived MVO was seen in 23 patients (34%). In the IVUS assessment,
      the frequency of plaque rupture, echolucent plaque, calcification and positive
      remodeling, and quantitative geometric data were not different between the MVO
      group and the no-MVO group. Although the frequency of plaque with ultrasound
      attenuation was similar between the 2 groups (87% vs. 89%, p = 0.999), the
      maximum attenuation angle (280 degrees  [range: 215 degrees  to 360 degrees ] vs.
      150 degrees  [range: 95 degrees  to 300 degrees ], p = 0.008) and attenuation
      length (11.3 mm [range: 7.2 to 17.8 mm] vs. 6.8 mm [range: 3.0 to 10.4 mm], p =
      0.009) were significantly greater in the MVO group than the no-MVO group.
      Multivariable logistic regression analysis showed that attenuated plaque with a
      maximum attenuation angle of >180 degrees  and attenuation length of >5 mm was an
      independent predictor of MVO (odds ratio: 6.07, 95% confidence interval: 1.89 to
      19.53, p = 0.002). CONCLUSIONS: Attenuated plaque with maximum attenuation angle
      of >180 degrees  and attenuation length of >5 mm was associated with the
      occurrence of MVO after primary PCI. IVUS might to be a useful tool for risk
      stratification in STEMI patients undergoing primary PCI.

PMID- 23871508
TI  - Does chronic warfarin cause increased blood loss and transfusion during lumbar
      spinal surgery?
AB  - BACKGROUND CONTEXT: The use of oral anticoagulation therapy such as warfarin is
      projected to increase significantly as the population ages and the prevalence of
      cardiovascular disease increases. Current recommendations state that warfarin be
      discontinued before surgery and the international normalized ratio (INR)
      normalized. PURPOSE: To determine if stopping warfarin 7 days before surgery and
      correcting INR had any effect on intraoperative blood loss or the requirements
      for blood product transfusion. STUDY DESIGN/SETTING: This was a retrospective
      cohort study in a high-volume tertiary care center. PATIENT SAMPLE: Sample
      comprised 263 consecutive patients who underwent elective lumbar spinal surgery.
      OUTCOME MEASURE: The outcome measures were intraoperative blood loss,
      intraoperative blood transfusion, postoperative blood transfusion, and the number
      of blood products transfused. METHODS: The records of patients undergoing
      elective spinal surgery were analyzed for patient demographic data,
      comorbidities, coagulation panel laboratory findings, operative characteristics,
      blood loss, and blood transfusion requirements. These included patients
      undergoing full laminectomies with or without posterolateral fusion and
      instrumentation. Patients on warfarin were analyzed for the mean dosage of
      warfarin and underlying pathology that required anticoagulation. All patients on
      warfarin had their anticoagulation therapy stopped 7 days before surgery and
      their INR checked preoperatively to confirm normalization. Both univariate and
      multiple linear regression analyses were performed. RESULTS: The patients on
      warfarin had a mean intraoperative blood loss of 839 mL compared with 441 mL for
      patients not on warfarin (p<.01). Multiple regression analysis determined that
      warfarin and number of spinal levels decompressed/fused/instrumented were
      predictors for increased blood loss (R(2)=0.37). Patients on warfarin also had
      increased postoperative blood transfusions (23.1% compared with 7.4%, p=.04).
      There was no significant difference between groups in terms of intraoperative
      blood transfusion or number of units transfused. CONCLUSIONS: Patients on chronic
      anticoagulation therapy with warfarin who have their therapy stopped 7 days
      before surgery and have their INR normalized still demonstrated increased
      intraoperative blood loss and requirement for postoperative transfusion. Surgeons
      should be aware of the increased propensity of these patients to bleed despite
      adherence to protocols and should attempt to mitigate this risk.

PMID- 23871510
TI  - Incidence, predictors, morphological characteristics, and clinical outcomes of
      stent edge dissections detected by optical coherence tomography.
AB  - OBJECTIVES: This study sought to investigate the frequency, predictors, and
      detailed qualitative and quantitative assessment of optical coherence tomography
      (OCT)-detected stent edge dissections. Its impact on subsequent management and
      clinical outcomes were also investigated. BACKGROUND: OCT is a high-resolution
      imaging modality that can lead to more frequent recognition and accurate
      assessment of vascular injuries during percutaneous coronary intervention (PCI).
      METHODS: From September 2010 to June 2011, all patients with OCT post-PCI were
      enrolled. Edge dissections were defined as disruptions of the arterial lumen
      surface in both the 5-mm distal and proximal stent edges. Qualitative and
      quantitative analyses of all edges were performed at 0.2-mm intervals. RESULTS:
      In total, 395 edges (249 lesions in 230 patients) were analyzed. The overall
      incidence of OCT-detected edge dissection was 37.8%, and most (84%) were not
      apparent on angiography. Independent predictors for OCT-detected dissections were
      presence of atherosclerotic plaque at stent edges, calcification angle, minimum
      fibrous cap thickness, thin-cap fibroatheromas, stent/lumen eccentricity, and
      vessel overstretching. Mean dissection length measured 2.04 +/- 1.60 mm, 96.2%
      appeared as flaps, and 52.8% extended beyond the intima/atheroma layer.
      Additional stenting was performed in 22.6% of all dissections, which were longer,
      had bigger dimensions, and promoted deeper vascular injury. The 12-month major
      adverse cardiac event rate was similar between patients with (7.95%) and without
      (5.69%, p = 0.581) dissections. CONCLUSIONS: High rates of stent edge dissections
      were detected by OCT, usually related to the presence of atherosclerosis at stent
      edges and to PCI technique. Detailed OCT assessment of dissection severity was
      possible and affected the subsequent management of this complication. Non-flow
      limiting, small, and superficial dissections left untreated proved benign.

PMID- 23871511
TI  - Complete revascularization is not a prerequisite for success in current
      transcatheter aortic valve implantation practice.
AB  - OBJECTIVES: This study sought to assess in patients undergoing transcatheter
      aortic valve implantation (TAVI), the prevalence and impact of incomplete
      coronary revascularization defined as >50% coronary artery or graft diameter
      stenosis on visual assessment of the coronary angiogram. BACKGROUND: TAVI is an
      established treatment option in elderly patients with aortic stenosis (AS) and a
      (very) high operative risk. Coronary artery disease (CAD) is often associated
      with AS. METHODS: A single-center cohort of consecutive patients undergoing TAVI
      between November 2005 and June 2012 was evaluated for the presence of significant
      CAD. The decision to revascularize and pursue complete revascularization was made
      by heart team consensus. RESULTS: A total of 263 consecutive patients with a mean
      age of 80 +/- 7 years and 51% male underwent TAVI with a median follow-up
      duration of 16 months (interquartile range: 4.2 to 28.1 months). Significant CAD
      with myocardium at risk was present in 124 patients (47%), 44 of whom had had
      previous coronary artery bypass grafting (CABG), and the median SYNTAX score in
      the 81 patients without previous CABG was 9.00 (2.38 to 15.63). Staged
      percutaneous coronary intervention (PCI) was planned in 19 (15%) and concomitant
      PCI with TAVI in 20 (16%). The median post-procedural residual SYNTAX score of
      patients without prior CABG was 5.00 (0.13 to 9.88). Overall, 99 patients (37%)
      (61 with no CABG and 38 CABG patients) had incomplete revascularization after
      TAVI. Revascularization status did not affect clinical endpoints. Kaplan-Meier
      survival curves for patients with and without complete revascularization
      demonstrated a 1-year mortality of 79.9% versus 77.4% (p = 0.85), respectively.
      CONCLUSIONS: In an elderly patient population undergoing TAVI for severe AS, a
      judicious revascularization strategy selection by a dedicated heart team can
      generate favorable mid-term outcome obviating the need for complete coronary
      revascularization.

PMID- 23871512
TI  - Costs of transradial percutaneous coronary intervention.
AB  - OBJECTIVES: This study sought to evaluate the costs of transradial percutaneous
      coronary intervention (TRI) and transfemoral percutaneous coronary intervention
      (TFI) from a contemporary hospital perspective. BACKGROUND: Whereas the TRI
      approach to percutaneous coronary intervention (PCI) has been shown to reduce
      access-site complications compared with TFI, whether it is associated with lower
      costs is unknown. METHODS: TRI and TFI patients were identified at 5 U.S.
      centers. The primary outcome was the cost of percutaneous coronary intervention
      (PCI) hospitalization, defined as cost on the day of PCI through hospital
      discharge. Cost was obtained from each hospital's cost accounting system.
      Independent costs of TRI were identified using propensity-scoring methods with
      inverse probability weighting. Secondary outcomes of interest were bleeding, in
      hospital mortality, and length of stay, which were stratified by pre-procedural
      risk and PCI indication. RESULTS: In 7,121 PCI procedures performed from January
      1, 2010, to March 31, 2011, TRI was performed in 1,219 (17%) patients and was
      associated with shorter lengths of stay (2.5 vs. 3.0 days; p < 0.001) and lower
      bleeding events (1.1% vs. 2.4%, adjusted odds ratio [OR]: 0.52, 95% confidence
      interval [CI]: 0.34 to 0.79; p = 0.002). TRI was associated with a total cost
      savings of $830 (95% CI: $296 to $1,364; p < 0.001), of which $130 (95% CI: -$99
      to $361; p = 0.112) were procedural savings and $705 (95% CI: $212 to $1,238; p <
      0.001) were post-procedural savings. There was an associated graded increase in
      savings among patients at higher predicted risk of bleeding: low risk: $642 (95%
      CI: $43 to $1,236; p = 0.035); moderate risk: $706 (95% CI: $104 to $1,308; p =
      0.029); and high risk: $1,621 (95% CI: $271 to $2,971, p = 0.039). CONCLUSIONS:
      TRI was associated with a cost savings exceeding $800 per patient relative to
      TFI. Increased adoption of TRI may result in cost savings at hospitals.

PMID- 23871513
TI  - Detection by near-infrared spectroscopy of large lipid core plaques at culprit
      sites in patients with acute ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: This study sought to describe near-infrared spectroscopy (NIRS)
      findings of culprit lesions in ST-segment elevation myocardial infarction
      (STEMI). BACKGROUND: Although autopsy studies demonstrate that most STEMI are
      caused by rupture of pre-existing lipid core plaque (LCP), it has not been
      possible to identify LCP in vivo. A novel intracoronary NIRS catheter has made it
      possible to detect LCP in patients. METHODS: We performed NIRS within the culprit
      vessels of 20 patients with acute STEMI and compared the STEMI culprit findings
      to findings in nonculprit segments of the artery and to findings in autopsy
      control segments. Culprit and control segments were analyzed for the maximum
      lipid core burden index in a 4-mm length of artery (maxLCBI(4mm)). RESULTS:
      MaxLCBI(4mm) was 5.8-fold higher in STEMI culprit segments than in 87 nonculprit
      segments of the STEMI culprit vessel (median [interquartile range (IQR)]: 523
      [445 to 821] vs. 90 [6 to 265]; p < 0.001) and 87-fold higher than in 279
      coronary autopsy segments free of large LCP by histology (median [IQR]: 523 [445
      to 821] vs. 6 [0 to 88]; p < 0.001).Within the STEMI culprit artery, NIRS
      accurately distinguished culprit from nonculprit segments (receiver-operating
      characteristic analysis area under the curve = 0.90). A threshold of maxLCBI(4mm)
      >400 distinguished STEMI culprit segments from specimens free of large LCP by
      histology (sensitivity: 85%, specificity: 98%). CONCLUSIONS: The present study
      has demonstrated in vivo that a maxLCBI(4mm) >400, as detected by NIRS, is a
      signature of plaques causing STEMI.

PMID- 23871515
TI  - AMPK: mediating the metabolic effects of salicylate-based drugs?
AB  - Salicylates are among the oldest medicinal compounds known to humans, and have
      been used to reduce fever, pain, and inflammation. The major oral salicylates are
      aspirin and salsalate, both of which are rapidly metabolized to salicylate in
      vivo. Owing to its acetyl group, aspirin irreversibly inhibits cyclo-oxygenases
      and thus blocks platelet aggregation, whereas salsalate has been used for
      treatment of inflammatory diseases such as rheumatoid arthritis. Recently,
      beneficial effects of salicylates in type 2 diabetes and cancer have been
      proposed. This has led to renewed interest in understanding how these simple
      molecules have such diverse and multifaceted effects. Here we discuss the idea
      that AMP-activated protein kinase (AMPK) might mediate some effects of salicylate
      based drugs, particularly by modulating cellular metabolism. 

PMID- 23871516
TI  - Medical ozone therapy for the inner ear acoustic trauma.
AB  - OBJECTIVES: The goal of the study was to look at the potential protective effect
      of ozone therapy by studying its antioxidant and vasodilatation effects against
      hearing loss caused by acoustic trauma. METHODS: Thirty-two male Wistar Albino
      rats were divided into four groups of eight. The 1st group was exposed to
      acoustic trauma, the 2nd group was treated with ozone initially, and was exposed
      to acoustic trauma 24 h later, the 3rd group received ozone without trauma, while
      the 4th group was the control group. The 1st and 2nd groups were exposed to
      acoustic trauma with 105 dB SPL white band noise for 4h. DPOAE and ABR tests were
      conducted in all groups on the 1st, 5th, and 10th days after trauma. RESULTS: In
      the 1st group, the effects of acoustic trauma continued on days 1, 5 and 10. The
      2nd group's DPOAE and ABR results on days 5 and 10 showed significant improvement
      at all frequencies compared to deterioration on day 1, and the readings were
      comparable to baseline measurements. CONCLUSION: Acoustic trauma is a pathology
      that is experienced frequently and leads to many problems in terms of health and
      cost. Ozone was demonstrated to be a reparative substance against acoustic trauma
      and, in addition, it can be supplied and applied easily.

PMID- 23871514
TI  - Monitoring tissue inflammation and responses to drug treatments in early stages
      of mice bone fracture using 50 MHz ultrasound.
AB  - Bone fracture induces moderate inflammatory responses that are regulated by
      cyclooxygenase-2 (COX-2) or 5-lipoxygenase (5-LO) for initiating tissue repair
      and bone formation. Only a handful of non-invasive techniques focus on monitoring
      acute inflammation of injured bone currently exists. In the current study, we
      monitored in vivo inflammation levels during the initial 2 weeks of the
      inflammatory stage after mouse bone fracture utilizing 50 MHz ultrasound. The
      acquired ultrasonic images were correlated well with histological examinations.
      After the bone fracture in the tibia, dynamic changes in the soft tissue at the
      medial-posterior compartment near the fracture site were monitored by ultrasound
      on the days of 0, 2, 4, 7, and 14. The corresponding echogenicity increased on
      the 2nd, 4th, and 7th day, and subsequently declined to basal levels after the
      14th day. An increase of cell death was identified by the positive staining of
      deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and was
      consistent with ultrasound measurements. The increases of both COX-2 and
      Leukotriene B4 receptor 1 (BLT1, 5-LO-relative receptor), which are regulators
      for tissue inflammation, in the immunohistochemistry staining revealed their
      involvement in bone fracture injury. Monitoring the inflammatory response to
      various non-steroidal anti-inflammatory drugs (NSAIDs) treatments was
      investigated by treating injured mice with a daily oral intake of aspirin (Asp),
      indomethacin (IND), and a selective COX-2 inhibitor (SC-236). The Asp treatment
      significantly reduced fracture-increased echogenicity (hyperechogenicity, p<0.05)
      in ultrasound images as well as inhibited cell death, and expression of COX-2 and
      BLT1. In contrast, treatment with IND or SC-236 did not reduce the
      hyperechogenicity, as confirmed by cell death (TUNEL) and expression levels of
      COX-2 or BLT1. Taken together, the current study reports the feasibility of a non
      invasive ultrasound method capable of monitoring post-fracture tissue
      inflammation that positively correlates with histological findings. Results of
      this study also suggest that this approach may be further applied to elucidate
      the underlying mechanisms of inflammatory processes and to develop therapeutic
      strategies for facilitating fracture healing.

PMID- 23871517
TI  - The effect of cleft palate repair technique on hearing outcomes in children.
AB  - OBJECTIVE: Otitis media with effusion causing conductive hearing loss is a
      problem for many children with cleft palate. This study examines the association
      between palate repair technique and hearing outcomes in children at 3 and 6 years
      post-repair. PATIENTS AND METHODS: Retrospective chart review of patients with
      all types of cleft palate that were repaired between 2001 and 2006 at a tertiary
      children's hospital. Exclusion criteria included sensorineural hearing loss,
      ossicular chain abnormalities, and ear canal abnormalities. The primary outcome
      was pure tone average (PTA) from 0.5 kHz to 2 kHz. RESULTS: 69 patients (138
      ears) were analyzed. 30.4% of left ears and 31.9% of right ears had an abnormal
      (>20 dB) PTA at 3 years; at 6 years this significantly improved to 13.0%
      (p=0.008) and 15.9% (p=0.011). Double-reverse z-plasty was associated with the
      lowest median PTA of 10.0 dB (p=0.046) at 6 years. There was no difference in
      median PTA between children with and without comorbid diagnoses (such as Pierre
      Robin Sequence, arthrogryposis) at either 3 years or 6 years (p=0.075, p=0.331).
      Multivariate model showed that extent of cleft influenced technique choice
      (p=0.027), but only technique choice was associated with significant differences
      in PTA and only at 6 years post-repair. CONCLUSION: The majority of children
      developed normal hearing by 6 years with palatoplasty and routine tube insertion.
      Double reverse z-plasty was associated with the best outcome, but is not ideal
      for hard palate clefts. Randomized controlled trials are needed to elucidate the
      relationship between technique, middle ear ventilation and time to recovery,
      irrespective of type of cleft.

PMID- 23871518
TI  - Expression of three novel cytochrome P450 (CYP) and antioxidative genes from the
      polychaete, Perinereis nuntia exposed to water accommodated fraction (WAF) of
      Iranian crude oil and benzo[a]pyrene.
AB  - To report a novel CYP genes and to evaluate its potency as a biomarker for oil
      pollution, we cloned three CYP genes and measured their expression profiles under
      controlled lab conditions using real-time reverse transcription PCR (real-time RT
      PCR) after exposure of the water accommodated fraction (WAF) of Iranian crude oil
      and benzo[alpha]pyrene (B[alpha]P) as a positive control. Of these, CYP432A1
      (CYP3 clan) gene was significantly induced by B[alpha]P exposure, indicating that
      the CYP3 clan gene would play an important role in polycyclic aromatic
      hydrocarbon (PAH) metabolisms, particularly for B[alpha]P in this species.
      However, the Perinereis nuntia CYP431A1 mRNA, a CYP2 clan gene, was sensitively
      expressed to WAF exposure with other two CYP genes. As one of Phase II
      detoxification enzymes, the glutathione S-transferase (GST) genes also
      upregulated with other antioxidant genes (SOD and CAT), indicating that WAF
      exposed P. nuntia was properly responding to this kind of chemical stress. Thus,
      three CYP genes from the polychaete, P. nuntia have a potential as a biomarker in
      monitoring of the marine sediment after an oil spill accident. 

PMID- 23871519
TI  - The mobilisation of sediment and benthic infauna by scallop dredges.
AB  - We present the results of experiments to assess the immediate impact of scallop
      dredging on the seabed sediment and on the inhabiting infauna. The passage of the
      scallop dredge is shown to homogenise the seabed, flattening sand ripples. The
      turbulent wake entrains up to the equivalent of a 1 mm layer of sediment per unit
      of swept width, although an analysis of the finer particles material implies that
      the suspended silt material must originate from depths of at least 10 mm. The
      species most abundant in the sediment plume either swim actively in the water
      column or are found in, or on, the upper layers of the substrate, whereas those
      most abundant in core samples taken from the sediment, but not present in the net
      samples, are almost all tube-building or deep burrowing. The vertical
      stratification of sediment concentration and of animal numbers in the water
      column suggests that even if some of these species respond actively to the
      presence of the dredge, once entrained, they are transported more or less
      passively in the same way as the larger sediment particles. There was no
      difference between the core samples taken before or after towing suggesting that
      animals mobilised by the dredge resettle in the tow path. Our analysis does not
      provide any information regarding the fate of these animals.

PMID- 23871520
TI  - Investigating perceptions of the academic educational environment across six
      undergraduate health care courses in the United Kingdom.
AB  - AIM: To compare how health care professional students perceive their academic
      learning environment in one Higher Education Institution (HEI). METHOD: The
      Dundee Ready Education Environment Measure (DREEM), a scale that measures
      students' perceptions of their academic classroom learning environments, and
      demographic items were completed by 673 undergraduate students enrolled in health
      professional courses at the University of Huddersfield, United Kingdom.
      Respondent scores, partitioned by demographic variables, were obtained on the
      total DREEM scale and on the individual sub-scales. Analysis of variance
      techniques were utilized to investigate associations between demographic
      variables on the total DREEM score and sub-scale scores. RESULTS: All students
      from all year levels reported total DREEM scores between 101 - 150, indicating a
      more positive than negative perception of their academic learning environments.
      Both profession and year of study were found to be significantly associated with
      total DREEM scores, with occupational therapists, physiotherapists and nurses
      scoring higher than operating department practice students; and first year
      students scoring higher than third year students. A significant interaction
      between these two factors was found to exist, indicating that the impact of the
      year of study does not apply equally over the different professional groups of
      students. CONCLUSIONS: Students in this study reported positive perceptions about
      their academic classroom learning environments and teaching delivered. Further
      interrogation of the DREEM sub-scale dimensions at a programme/cohort level may
      offer course teams' further information to inform continuous quality improvement.

PMID- 23871521
TI  - [Controlateral prophylactic mastectomy: on which arguments?].

PMID- 23871522
TI  - Hydrothermal synthesis of hydroxyapatite plates prepared using low molecular
      weight heparin (LMWH).
AB  - Materials with enhanced physical and biological properties have been used for
      biomedical applications and can be developed by functionalizing them using
      various components. Hydroxyapatite (HAP), among other available synthetic
      material, serves as one of the best tools in orthopaedics and ceramic coatings.
      The porous structure of HAP helps in bone cell regeneration, chemical integration
      of bone and also favours the interaction between bone and tissues. Herein, we
      have demonstrated a simple procedure for the synthesis of HAP using low molecular
      weight heparin (LMWH), a structural analogue of bone heparan sulphate
      proteoglycan. The presence of small sized HAP plates with well-defined structures
      was revealed using electron microscopic analysis. The phase purity of the
      synthesized HAP was evaluated using X-ray diffraction pattern obtained before and
      after immersion in simulated body fluid (SBF). 

PMID- 23871523
TI  - Trunk strength, muscle activity and spinal loads in maximum isometric flexion and
      extension exertions: a combined in vivo-computational study.
AB  - Determination of the trunk maximum voluntary exertion moment capacity and
      associated internal spinal forces could serve in proper selection of workers for
      specific occupational task requirements, injury prevention and treatment outcome
      evaluations. Maximum isometric trunk exertion moments in flexion and extension
      along with surface EMG of select trunk muscles are measured in 12 asymptomatic
      subjects. Subsequently and under individualized measured harness-subject forces,
      kinematics and upper trunk gravity, an iterative kinematics-driven finite element
      model is used to compute muscle forces and spinal loads in 4 of these subjects.
      Different co-activity and intra-abdominal pressure levels are simulated. Results
      indicate significantly larger maximal resistant moments and spinal
      compression/shear forces in extension exertions than flexion exertions. The
      agonist trunk muscles reach their maximum force generation (saturation) to
      greater extent in extension exertions compared to flexion exertions. Local lumbar
      extensor muscles are highly active in extension exertions and generate most of
      the internal spinal forces. The maximum exertion attempts produce large spinal
      compression and shear loads that increase with the antagonist co-activity level
      but decrease with the intra-abdominal pressure. Intra-abdominal pressure
      decreases agonist muscle forces in extension exertions but generally increase
      them in flexion exertions. 

PMID- 23871524
TI  - Editorial comment.

PMID- 23871525
TI  - Re: Early detection of prostate cancer: AUA guideline: H. B. Carter, P. C.
      Albertsen, M. J. Barry, R. Etzioni, S. J. Freedland, K. L. Greene, L. Holmberg,
      P. Kantoff, B. R. Konety, M. H. Murad, D. F. Penson and A. L. Zietman J Urol
      2013; 190: 419-426.

PMID- 23871527
TI  - Mediastinal Castleman's disease: case report.

PMID- 23871526
TI  - Obstructive sleep apnea in normal weight patients: characteristics and comparison
      with overweight and obese patients.
AB  - OBJECTIVE: To determine the frequency of obstructive sleep apnoea (OSA) and
      metabolic syndrome (MS) in normal weight patients and their characteristics, and
      to compare these with overweight and obese patients. METHODS: We studied all
      patients with suspected OSA referred to the sleep laboratory from January to
      December 2009. OSA was diagnosed when the apnoea-hypopnoea index (AHI) was >5 and
      symptoms were present. MS was diagnosed according to International Diabetes
      Federation (IDF) criteria. The patients were distributed into 3 groups according
      to body mass index (BMI): normal weight (<25kg/m(2)), overweight (25-29.9kg/m(2))
      and obese (>=30kg/m(2)). RESULTS: We studied 475 patients: 7.60% normal weight
      and 56.4% obese. Most patients in the normal weight group were women, snorers,
      non-smokers, non-drinkers and were significantly younger and with a smaller neck
      and waist circumference than obese and overweight patients. OSA was diagnosed in
      90.10%: 77.70% normal weight. OSA in these patients was mostly mild, and there
      were differences between the diagnosis of OSA and the BMI classified. MS was
      diagnosed in 64.40%: 33.33% normal weight. There was a higher probability of MS
      as the BMI increased. OSA and MS frequency in normal weight patients was 22% and
      in obese patients was 70.52%. OSA in normal weight patients was related with
      gender and age. There was no relationship between OSA and MS, or between
      otorhinolaryngological malformations and OSA in normal weight patients. Eight
      normal weight patients with OSA were treated with continuous positive airway
      pressure (CPAP) therapy. CONCLUSIONS: The frequency of OSA in normal weight
      patients was lower than in overweight and obese patients. The frequency of
      concomitant OSA and MS was lower in normal weight patients than in obese
      subjects. Normal weight patients were mostly women, younger and had no toxic
      habits. In normal weight patients, age and gender were predictive factors for
      OSA, but OSA and MS were not related.

PMID- 23871528
TI  - Critical role of nutrition in improving quality of care: an interdisciplinary
      call to action to address adult hospital malnutrition.
AB  - The current era of health care delivery, with its focus on providing high
      quality, affordable care, presents many challenges to hospital-based health
      professionals. The prevention and treatment of hospital malnutrition offers a
      tremendous opportunity to optimize the overall quality of patient care, improve
      clinical outcomes, and reduce costs. Unfortunately, malnutrition continues to go
      unrecognized and untreated in many hospitalized patients. This article represents
      a call to action from the interdisciplinary Alliance to Advance Patient Nutrition
      to highlight the critical role of nutrition intervention in clinical care and to
      suggest practical ways to promptly diagnose and treat malnourished patients and
      those at risk for malnutrition. We underscore the importance of an
      interdisciplinary approach to addressing malnutrition both in the hospital and in
      the acute post-hospital phase. It is well recognized that malnutrition is
      associated with adverse clinical outcomes. Although data vary across studies,
      available evidence shows that early nutrition intervention can reduce
      complication rates, length of hospital stay, readmission rates, mortality, and
      cost of care. The key is to systematically identify patients who are malnourished
      or at risk and to promptly intervene. We present a novel care model to drive
      improvement, emphasizing the following six principles: (1) create an
      institutional culture where all stakeholders value nutrition; (2) redefine
      clinicians' roles to include nutrition care; (3) recognize and diagnose all
      malnourished patients and those at risk; (4) rapidly implement comprehensive
      nutrition interventions and continued monitoring; (5) communicate nutrition care
      plans; and (6) develop a comprehensive discharge nutrition care and education
      plan. 

PMID- 23871529
TI  - Reply: To PMID 23245482.

PMID- 23871530
TI  - Central slip tenotomy for chronic mallet finger.
AB  - We performed a retrospective audit of a consecutive series of twenty-three
      patients to evaluate the results of central slip tenotomy performed for chronic
      mallet finger. The surgery was performed at a mean of 42 (range four to 480)
      months after surgery and the pre-operative extensor lag at the distal
      interphalangeal joint was a mean of 44 (range 20-80) degrees. At the time of
      evaluation, at a mean of 33 (range six to 95) months after surgery, the extensor
      lag had improved to a mean of seven (range zero to 40) degrees. Using a simple
      clinical grading system, there were 12 excellent, six good, three fair and two
      poor results. Three patients had complications; one infection requiring
      antibiotics, and two who had post-operative extensor lags at the proximal
      interphalangeal joint which responded to a period of splinting and hand therapy. 

PMID- 23871531
TI  - Breast phyllodes tumor: a review of literature and a single center retrospective
      series analysis.
AB  - PURPOSE: Complete surgical resection is the standard treatment for localized
      breast phyllodes tumors. Post-surgical treatments are still a matter of debate.
      We carried out an overview of the literature to investigate the clinical outcome
      of patients with phyllodes tumor. A retrospective analysis of mono-institutional
      series has been included as well. METHODS: We reviewed all the retrospective
      series reported from 1951 until April 2012. We analyzed cases treated at our
      institution from 1999 to 2010. RESULTS: Eighty-three articles (5530 patients;
      1956 malignant tumors) were reviewed. Local recurrences were independent of
      histology. Distant recurrences were more frequent in the malignant tumors (22%).
      A total of 172 phyllodes tumors were included in the retrospective analysis.
      DISCUSSION: Prognosis of phyllodes tumors is excellent. There are no convincing
      data to recommend any adjuvant treatment after surgery. Molecular
      characterization may well provide new clues to permit identification of active
      treatments for the rare poor prognosis cases.

PMID- 23871532
TI  - Challenges, expectations and limits for nanoparticles-based therapeutics in
      cancer: a focus on nano-albumin-bound drugs.
AB  - Improving the efficacy-toxicity balance of anticancer agents remains an ongoing
      challenge in oncology. Beside the ever-growing development of innovative drugs
      addressing newly discovered molecular targets, nanotechnologies provide today a
      promising and exciting strategy to achieve this goal. The idea of carrying active
      compounds to their respective targets so as to improve their efficacy while
      sparing healthy tissue and reducing side-effects is not new. However, this area
      of research is in constant rise, and benefits from the latest advances in the
      field of biopharmaceutics, medicinal chemistry and nanomedicine. In addition to
      anthracyclines already widely present as liposomal drugs on the shelves, a
      variety of anticancer drugs can be now encapsulated into different chemical of
      structures so as to enhance their specificity toward malignant cells, mainly
      through improved pharmacokinetics profiles. Indeed, the recent advances in
      chemistry allow now a wide variety of scaffolds to be used as drug-carriers, so
      as optimize the delivery of cytotoxics. Even more recently, conjugated-drugs such
      as nanoalbumin (Nab) conjugates have emerged as a new promising alternative to
      improve both anticancer drugs distribution in the body and efficacy/toxicity
      balance eventually. This review covers the achievements and current limits of
      nanoparticles in oncology, with a special focus on nab-paclitaxel as a
      paradigmatic drug for this new generation of conjugated entities.

PMID- 23871533
TI  - Authors' response to Dr. Joseph Troisi's commentary on "Assessment of the
      interoceptive effects of alcohol in rats using short-term training procedures".

PMID- 23871535
TI  - The Pavlovian vs. operant interoceptive stimulus effects of EtOH: commentary on
      Besheer, Fisher, & Durant (2012).

PMID- 23871534
TI  - Neonatal ethanol exposure results in dose-dependent impairments in the
      acquisition and timing of the conditioned eyeblink response and altered
      cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.
AB  - Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the
      cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction
      in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a
      simple motor learning task in which a neutral conditioned stimulus (CS; tone) is
      repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital
      shock). Across training, cell populations in the interpositus (IP) nucleus model
      the temporal form of the eyeblink-conditioned response (CR). The hippocampus,
      though not required for delay EBC, also shows learning-dependent increases in CA1
      and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or
      5 mg/kg/day of ethanol during postnatal days (PD) 4-9. As adults, CR acquisition
      and timing were assessed during 6 training sessions of delay EBC with a short
      (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by
      another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in
      the IP and area CA1 during all 12 sessions. The high-dose rats learned the most
      slowly and, with the moderate-dose rats, produced the longest CR peak latencies
      over training to the short ISI. The low dose of alcohol impaired CR performance
      to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of
      ethanol) rats also showed slower-than-normal increases in learning-dependent
      excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats
      showed a higher rate of CR production to the long ISI and enhanced IP and CA1
      activation when compared to the 3E and 5E rats. The results indicate that binge
      like ethanol exposure in neonatal rats induces long-lasting, dose-dependent
      deficits in CR acquisition and timing and diminishes conditioning-related
      neuronal excitation in both the cerebellum and hippocampus. 

PMID- 23871536
TI  - Toll-like receptor 4 increases intestinal permeability through up-regulation of
      membrane PKC activity in alcoholic steatohepatitis.
AB  - Intestinal hyperpermeability is a causal factor for the development of alcoholic
      endotoxemia and steatohepatitis. However, the mechanisms governing this link
      remain unknown. The purpose of this study was to determine whether toll-like
      receptor 4 (TLR4) is involved in ethanol's deleterious effects on the intestinal
      barrier. Caco-2 cells were incubated in vitro with 1-10% ethanol. The results
      indicated that ethanol had a dose-dependent effect in increasing TLR4 expression
      and intercellular permeability. Then the effects of TLR4 on protein kinase C
      (PKC) and the intercellular junction protein occludin were assessed with and
      without pretreatment with a TLR4 inhibitor. The results indicated that TLR4
      increased nonspecific PKC activity and reduced the expression of phosphorylated
      occludin in the membrane, which increased intercellular permeability. These
      effects were prevented by pretreatment with TLR4 mAb. Wild-type C57BL/6 mice were
      fed an ethanol or isocaloric liquid diet for 6 weeks. Hepatitis was diagnosed by
      the presence of an associated elevated blood endotoxin level. Chronic ethanol
      treatment significantly elevated blood endotoxin levels, intestinal permeability,
      and the expression of TLR4 in the ileum and colon. Moreover, ethanol exposure
      reduced the distribution of phosphorylated occludin in the intestinal epithelium
      because of PKC activation. In conclusion, chronic ethanol exposure induces a high
      response of TLR4 to lipopolysaccharide (LPS), and TLR4 increases intestinal
      permeability through down-regulation of phosphorylated occludin expression in the
      intestinal epithelial barrier, accompanied by membrane PKC hyperactivity. 

PMID- 23871537
TI  - Impact of cell purification technique of autologous human adult stem cells on
      inflammatory reaction.
AB  - Adult stem cells have shown fantastic regenerative potential as the cellular
      components of biomaterial mediated tissue engineering. Realising the biomedical
      potential of human adult stem cells (hASCs) however will require delivery in an
      ultra- purified format, without competing cells which may mediate inflammation,
      fibrosis or tumorigenesis. Purifying ASCs involves exhuming cells from primary
      tissue using immunoaffinity; which isolates pure populations with the
      complication of retained immunoglobulin (Ig); the clinical impact of which is
      currently not known. One of the negative outcomes of retained surface Ig is
      exacerbation of inflammation by leucocyte Fc receptor (FcR) activation, with
      consequences ranging from inflammatory cytokine and ROS release to chronic
      inflammation. The balance of ROS within a tissue will impact the efficacy of a
      stem cell therapy as ROS play an important role in stem cell self renewal and
      differentiation. In this study we utilised a chemiluminescent monitoring
      technique based on a ROS excitable photoprotein Pholasin, to quantify leucocyte
      ROS production in response to xenogeneic and recombinant human Ig of varying
      class and isotype with applications in stem cell selection. We were able to
      demonstrate inter-class differences in leucocyte ROS response to Ig which also
      varied between donors. This study highlighted the potential for utilising this
      technique for personalisation of autologous ASC therapies. This would allow
      clinicians to perform a rapid pre-operative screen to maximise the probability
      for success of an ASC intervention based on cell isolation using an Ig most
      appropriate for a specific patient.

PMID- 23871538
TI  - Indocyanine green loaded SPIO nanoparticles with phospholipid-PEG coating for
      dual-modal imaging and photothermal therapy.
AB  - A biodegradable nanotheranostic agent has been successfully constructed for
      fluorescence/magnetic resonance dual-modal imaging guided photothermal therapy by
      loading indocyanine green (ICG) molecules into 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG) coated
      superparamagnetic iron oxide (SPIO) nanoparticles (NPs). It was proved that the
      obtained SPIO@DSPE-PEG/ICG NPs with an average diameter around 27.4 nm could
      serve as an efficient probe to simultaneously enhance fluorescence imaging and
      magnetic resonance imaging greatly in vivo. After tail vein injection, the
      SPIO@DSPE-PEG/ICG NPs were found selectively accumulate at the tumor site.
      Encapsulation of ICG into the lipid coating of SPIO NPs results in higher
      photostability than free ICG due to the protection from degradation. SPIO@DSPE
      PEG/ICG NPs exhibited significant photothermal cytotoxicity. Cancer cells could
      be killed in vitro and tumors could be ablated in vivo efficiently through
      photothermal effects of SPIO@DSPE-PEG/ICG NPs under laser irradiation. In
      summary, SPIO@DSPE-PEG/ICG NPs integrate multiple capabilities for effective
      tumor imaging and therapy. This is very helpful for accurately interpreting the
      obtained images, identifying the size and location of the tumor, as well as
      guiding and monitoring the photothermal therapy through a single agent.

PMID- 23871539
TI  - Exploring the mesenchymal stem cell niche using high throughput screening.
AB  - In the field of stem cell technology, future advancements rely on the effective
      isolation, scale-up and maintenance of specific stem cell populations and robust
      procedures for their directed differentiation. The stem cell microenvironment -
      or niche - encompasses signal inputs from stem cells, supporting cells and from
      the extracellular matrix. In this context, the contribution of physicochemical
      surface variables is being increasingly recognised. This paradigm can be
      exploited to exert control over cellular behaviour. However, the number of
      parameters at play, and their complex interactions, presents a formidable
      challenge in delineating how the decisions of cell fate are orchestrated within
      the niche. Additionally, in the case of mesenchymal stem cells (MSC), more than
      one type of stem cell niche has been identified. By employing high throughput
      screening (HTS) strategies, common and specific attributes of each MSC niche can
      be probed. Here, we explore biological, chemical and physical parameters that are
      known to influence MSC self-renewal and differentiation. We then review
      techniques and strategies that allow the HTS of surface properties for conditions
      that direct stem cell fate, using MSC as a case study. Finally, challenges in
      recapturing the niche, particularly its three dimensional nature, in surface
      based HTS formats are discussed. 

PMID- 23871540
TI  - Engineered magnetic hybrid nanoparticles with enhanced relaxivity for tumor
      imaging.
AB  - Clinically used contrast agents for magnetic resonance imaging (MRI) suffer by
      the lack of specificity; short circulation time; and insufficient relaxivity.
      Here, a one-step combinatorial approach is described for the synthesis of
      magnetic lipid-polymer (hybrid) nanoparticles (MHNPs) encapsulating 5 nm ultra
      small super-paramagnetic iron oxide particles (USPIOs) and decorated with Gd(3+)
      ions. The MHNPs comprise a hydrophobic poly(lactic acid-co-glycolic acid) (PLGA)
      core, containing up to ~5% USPIOs (w/w), stabilized by lipid and polyethylene
      glycol (PEG). Gd(3+) ions are directly chelated to the external lipid monolayer.
      Three different nanoparticle configurations are presented including Gd(3+)
      chelates only (Gd-MHNPs); USPIOs only (Fe-MHNPs); and the combination thereof
      (MHNPs). All three MHNPs exhibit a hydrodynamic diameter of about 150 nm. The Gd
      MHNPs present a longitudinal relaxivity (r1 = 12.95 +/- 0.53 (mM s)(-1)) about
      four times larger than conventional Gd-based contrast agents (r1 = 3.4 (mM s)(
      1)); MHNPs have a transversal relaxivity of r2 = 164.07 +/- 7.0 (mM s)(-1), which
      is three to four times larger than most conventional systems (r2 ~ 50 (mM s)(
      1)). In melanoma bearing mice, elemental analysis for Gd shows about 3% of the
      injected MHNPs accumulating in the tumor and 2% still circulating in the blood,
      at 24 h post-injection. In a clinical 3T MRI scanner, MHNPs provide significant
      contrast confirming the observed tumor deposition. This approach can also
      accommodate the co-loading of hydrophobic therapeutic compounds in the MHNP core,
      paving the way for theranostic systems.

PMID- 23871541
TI  - Biodegradable cationic nanoparticles loaded with an anticancer drug for deep
      penetration of heterogeneous tumours.
AB  - To enhance limited drug penetration that mediated drug resistance and
      heterogeneity within the tumour microenvironment, we designed a paclitaxel (PTX)
      loaded degradable cationic nanogel (DpNG) consisted with acetylated pullulan and
      low molecular weight polyethyleneimine ((Low)bPEI, 1.8 kDa). The restoration of
      cationic charge on the DpNG was achieved via HA degradation by hyaluronidase
      which is secreted in tumour. The size and surface charge of HA-coated DpNG loaded
      with PTX (HA/DpNG-PTX) was 200-250 nm and 0 mV, respectively. The DpNG-PTX was
      showed significant cytotoxicity in heterogeneous cancer cells. The IC50 value of
      DpNG-PTX was 100 times less than that of free PTX. The growth of heterogeneous
      tumour in Balb/c mice was inhibited via intravenous injection of HA/DpNG-PTX.
      Furthermore, the invasive distance and amount of HA/DpNG-PTX localised within the
      deep tissue regions were increased two times than that of PA-PTX. Therefore, the
      DpNG based drug delivery system could be useful for treatment of heterogeneous
      tumour.

PMID- 23871543
TI  - Abrasion and fatigue resistance of PDMS containing multiblock polyurethanes after
      accelerated water exposure at elevated temperature.
AB  - Segmented polyurethane multiblock polymers containing polydimethylsiloxane and
      polyether soft segments form tough and easily processed thermoplastic elastomers
      (PDMS-urethanes). Two commercially available examples, PurSil 35 (denoted as P35)
      and Elast-Eon E2A (denoted as E2A), were evaluated for abrasion and fatigue
      resistance after immersion in 85  degrees C buffered water for up to 80 weeks. We
      previously reported that water exposure in these experiments resulted in a molar
      mass reduction, where the kinetics of the hydrolysis reaction is supported by a
      straight forward Arrhenius analysis over a range of accelerated temperatures (37
      85  degrees C). We also showed that the ultimate tensile properties of P35 and
      E2A were significantly compromised when the molar mass was reduced. Here, we show
      that the reduction in molar mass also correlated with a reduction in both the
      abrasion and fatigue resistance. The instantaneous wear rate of both P35 and E2A,
      when exposed to the reciprocating motion of an ethylene tetrafluoroethylene
      (ETFE) jacketed cable, increased with the inverse of the number averaged molar
      mass (1/Mn). Both materials showed a change in the wear surface when the number
      averaged molar mass was reduced to ~ 16 kg/mole, where a smooth wear surface
      transitioned to a 'spalling-like' pattern, leaving the wear surface with ~ 0.3 mm
      cracks that propagated beyond the contact surface. The fatigue crack growth rate
      for P35 and E2A also increased in proportion to 1/Mn, after the molar mass was
      reduced below a critical value of ~30 kg/mole. Interestingly, this critical molar
      mass coincided with that at which the single cycle stress-strain response changed
      from strain hardening to strain softening. The changes in both abrasion and
      fatigue resistance, key predictors for long term reliability of cardiac leads,
      after exposure of this class of PDMS-urethanes to water suggests that these
      materials are susceptible to mechanical compromise in vivo.

PMID- 23871542
TI  - The use of bioinspired alterations in the glycosaminoglycan content of collagen
      GAG scaffolds to regulate cell activity.
AB  - The design of biomaterials for regenerative medicine can require biomolecular
      cues such as growth factors to induce a desired cell activity. Signal molecules
      are often incorporated into the biomaterial in either freely-diffusible or
      covalently-bound forms. However, biomolecular environments in vivo are often
      complex and dynamic. Notably, glycosaminoglycans (GAGs), linear polysaccharides
      found in the extracellular matrix, are involved in transient sequestration of
      growth factors via charge interactions. Biomaterials mimicking this phenomenon
      may offer the potential to amplify local biomolecular signals, both endogenously
      produced and exogenously added. GAGs of increasing sulfation (hyaluronic acid,
      chondroitin sulfate, heparin) were incorporated into a collagen-GAG (CG) scaffold
      under development for tendon tissue engineering. Manipulating the degree of GAG
      sulfation significantly impacts sequestration of growth factors from the media.
      Increasing GAG sulfation improved equine tenocyte metabolic activity in normal
      serum (10% FBS), low serum (1% FBS), and IGF-1 supplemented media conditions.
      Notably, previously reported dose-dependent changes in tenocyte bioactivity to
      soluble IGF-1 within the CG scaffold were replicated by using a single dose of
      soluble IGF-1 in scaffolds containing increasingly sulfated GAGs. Collectively,
      these results suggest that CG scaffold GAG content can be systematically
      manipulated to regulate the sequestration and resultant enhanced bioactivity of
      growth factor signals on cell behavior within the matrix.

PMID- 23871544
TI  - The promotion of osteoclastogenesis by sulfated hyaluronan through interference
      with osteoprotegerin and receptor activator of NF-kappaB ligand/osteoprotegerin
      complex formation.
AB  - In order to improve bone regeneration, in particular in aged and multimorbid
      patients, the development of new adaptive biomaterials and their characterization
      in terms of their impact on bone biology is warranted. Glycosaminoglycans (GAGs)
      such as hyaluronan (HA) are major extracellular matrix (ECM) components in bone
      and may display osteogenic properties that are potentially useful for biomaterial
      coatings. Using native and synthetically derived sulfate-modified HA, we
      evaluated how GAG sulfation modulates the activity of two main regulators of
      osteoclast function: receptor activator of NF-kappaB ligand (RANKL) and
      osteoprotegerin (OPG). GAGs were tested for their capability to bind to OPG and
      RANKL using surface plasmon resonance (SPR), ELISA and molecular modeling
      techniques. Results were validated in an in vitro model of osteoclastogenesis.
      Sulfated GAGs bound OPG but not RANKL in a sulfate-dependent manner. Furthermore,
      OPG pre-incubated with different GAGs displayed a sulfate- and dose-dependent
      loss in bioactivity, possibly due to competition of GAGs for the RANKL/OPG
      binding site revealing a potential GAG interaction site at the RANKL/OPG
      interface. In conclusion, high-sulfated GAGs might significantly control
      osteoclastogenesis via interference with the physiological RANKL/OPG complex
      formation. Whether these properties can be utilized to improve bone regeneration
      and fracture healing needs to be validated in vivo.

PMID- 23871545
TI  - Characterisation of the Mycobacterium tuberculosis alternative sigma factor SigG:
      its operon and regulon.
AB  - A major step in the pathogenesis of Mycobacterium tuberculosis is the ability to
      survive inside macrophages, where it is exposed to a number of DNA damaging
      agents. The alternative sigma factor SigG has been shown to be upregulated by DNA
      damaging agents and by macrophage infection, but not to regulate genes of the DNA
      repair pathway. Here we show that SigG is expressed from at least two promoters,
      the most dominant of these being the DNA damage inducible RecA_Ndp promoter. This
      promoter is located within the annotated coding region of SigG and so the correct
      translational start site was determined experimentally and found to be 114 bp
      downstream of the annotated start site. Examining the gene expression profile of
      a SigG over-expression strain found a small number of genes to up-regulated, two
      of these encoded proteins containing glyoxylase-like domains. 

PMID- 23871546
TI  - A developmental ontology for the mammalian brain based on the prosomeric model.
AB  - In the past, attempts to create a hierarchical classification of brain structures
      (an ontology) have been limited by the lack of adequate data on developmental
      processes. Recent studies on gene expression during brain development have
      demonstrated the true morphologic interrelations of different parts of the brain.
      A developmental ontology takes into account the progressive rostrocaudal and
      dorsoventral differentiation of the neural tube, and the radial migration of
      derivatives from progenitor areas, using fate mapping and other experimental
      techniques. In this review, we used the prosomeric model of brain development to
      build a hierarchical classification of brain structures based chiefly on gene
      expression. Because genomic control of neural morphogenesis is remarkably
      conservative, this ontology should prove essentially valid for all vertebrates,
      aiding terminological unification. 

PMID- 23871547
TI  - Studies to control biofilm formation by coupling ultrasonication of natural
      waters and anodization of titanium.
AB  - The main objective of this study was to investigate the combined effect of
      ultrasonication of natural waters and anodization of titanium on microbial
      density and biofilm formation tendency on titanium surfaces. Application of 24
      kHz, 400 W high power ultrasound through a 14 mm horn type SS (stainless steel)
      Sonicator with medium amplitude of 60% for 30 min brought about three order
      decrease in total bacterial density of laboratory tap water, cooling tower water
      and reservoir water and two order decrease in seawater. Studies on the effect of
      ultrasonication on dilute pure cultures of Gram-negative and Gram-positive
      bacteria showed five order and three order decrease for Pseudomonas sp. and
      Flavobacterium sp. respectively and two order and less than one order decrease
      for Bacillus sp. and Micrococcus sp. respectively. Ultrasonication increased lag
      phase and reduced logarithmic population increase and specific growth rate of
      Gram-negative bacteria whereas for Gram-positive bacteria specific growth rate
      increased. Studies on the biofilm formation tendency of these ultrasonicated
      mediums on titanium surface showed one order reduction under all conditions.
      Detailed biofilm imaging by advanced microscopic techniques like AFM, SEM and
      epifluorescence microscopy clearly visualized the lysed/damaged cells and
      membrane perforations due to ultrasonication. Combination of ultrasonication and
      anodization brought about maximum decrease in bacterial density and biofilm
      formation with greater than two order decrease in seawater, two order decrease in
      Bacillus sp. culture and more than four order decrease in Flavobacterium sp.
      culture establishing the synergistic effect of anodization and ultrasonication in
      this study.

PMID- 23871548
TI  - The impact of aerosolized mucolytic agents on the airflow resistance of bacterial
      filters used in mechanical ventilation.
AB  - BACKGROUND/PURPOSE: In order to reduce the contamination in the ventilator,
      bacterial filters were placed on the expiratory limb of a ventilator circuit.
      Aerosolized mucolytic agents may increase the resistance of the ventilator. The
      goal of this study is to determine the impact of aerosolized mucolytic agents on
      the pressure change during mechanical ventilation. METHODS: A lung model was
      investigated with mucolytic inhaled agents of 10% acetylcysteine and 2%
      hypertonic saline. The agents were administered using a jet nebulizer every 45
      minutes for 15 minutes. The pressure drop was measured after nebulization. The
      end point was referred to the 45(th) dose or obstruction of the filter.
      Furthermore, the pressure drop after steam autoclaving was also measured.
      RESULTS: The maximum pressure was significantly higher with 10% acetylcysteine
      than with 2% sodium chloride (39.32 +/- 7.22 cmH2O vs. 3.53 +/- 0.90 cmH2O, p <
      0.001). With acetylcysteine filters, the pressure drop over 4 cmH2O occurred
      earlier and had a good relationship between the degree of pressure drop and
      doses. The acetylcysteine group yielded a significant difference in the pressure
      drop compared to the newly autoclaved and the end point of inhalation (p =
      0.043). CONCLUSION: This study demonstrated the aerosolized mucolytic agents
      could increase the pressure drop of the bacterial filters during mechanical
      ventilation. The pressure drop of the bacterial filters was higher with 10%
      acetylcysteine. It is critical to continuously monitor the expiration resistance,
      auto-positive end-expiratory pressure, and ventilator output waveform when
      aerosolized 10% acetylcysteine was used in mechanical ventilation patients.

PMID- 23871549
TI  - Change and predictors of symptom distress in breast cancer patients following the
      first 4 months after diagnosis.
AB  - BACKGROUND/PURPOSE: Breast cancer patients may encounter a wide range of physical
      and psychosocial distress symptoms during diagnosis, while awaiting treatment,
      and during treatment. This study of newly diagnosed breast cancer patients
      explores: (1) changes in symptom distress over 4 months; and (2) factors
      predicting changes in symptom distress. METHODS: A prospective longitudinal
      design was used to collect data from breast cancer patients in northern Taiwan. A
      set of questionnaires was used to measure anxiety, symptom distress, social
      support, and demographic and treatment-related characteristics. Repeated measures
      analysis of variance (RM-ANOVA) with least significant difference (LSD) was used
      to examine differences in symptom distress, state anxiety, and social-support
      levels across four time-points. Generalized estimating equation (GEE) is used to
      determine predictors for the change in symptom distress. RESULTS: Participants
      showed mild overall symptom distress during treatment that increased from cancer
      diagnosis to treatment phases, with a peak at 4 months after diagnosis. Insomnia
      was the most commonly identified distressful symptom over time. Changes in
      overall symptom distress were significantly predicted by state anxiety, health
      professional support, and time since cancer diagnosis. CONCLUSION: Change in
      symptom distress following the first 4 months after diagnosis was predicted by
      state anxiety, health professional support, and time. Patients should receive
      social support and be trained in problem-solving skills to relieve distressful
      symptoms from diagnosis through treatment.

PMID- 23871550
TI  - Environmental tobacco smoke and arsenic methylation capacity are associated with
      urothelial carcinoma.
AB  - BACKGROUND/PURPOSE: Cigarette smoking, exposure to secondhand smoke, and arsenic
      exposure are well known risk factors for developing urothelial carcinoma (UC). We
      investigated the combined effects of cigarette smoking, exposure to secondhand
      smoke, and the presence of urinary total arsenic on the risk of developing UC.
      METHODS: We conducted a hospital-based, case-control study involving 261 UC
      patients and 672 cancer-free control individuals between September 2002 and May
      2009. RESULTS: Individuals who had smoked <100 cigarettes in their lifetime
      (never smokers) and had a high urinary total arsenic level (>=15.40 MUg/g
      creatinine), and those who had smoked >100 cigarettes in their lifetime (ever
      smokers) and had a high urinary total arsenic level, had increased risks of
      developing UC (3.20-fold and 6.45-fold greater), respectively, compared to
      individuals who were never smokers and had a low urinary total arsenic level.
      Individuals who had high urinary total arsenic levels and had been exposed to
      secondhand smoke, and individuals with high urinary arsenic levels who had not
      been exposed to secondhand smoke, had increased chances (2.71-fold and 5.00-fold
      greater, respectively) of developing UC, compared to individuals who were not
      exposed to secondhand smoke and had low urinary total arsenic levels. Ever
      smokers who had been exposed to secondhand smoke and had a high urinary total
      arsenic level had the greatest increased risk for developing UC (10.82-fold
      greater). CONCLUSION: Individuals in a Taiwanese population who smoked
      cigarettes, were exposed to secondhand smoke, and a high urinary total arsenic
      level, had a significant risk for developing UC.

PMID- 23871551
TI  - Developing a disability determination model using a decision support system in
      Taiwan: a pilot study.
AB  - BACKGROUND/PURPOSE: The aims of our study were to: (1) develop the Disability
      Grading Decision Support System (DGDSS) and to (2) compare the new International
      Classification of Functioning, Disability, and Health (ICF)-based disability
      determination tool (ICF-DDT) with the diagnosis-based disability determination
      tool (D-DDT). METHODS: A total of 9357 patients recruited from 236 accredited
      institutions were evaluated using the ICF-DDT and the D-DDT, and the presence,
      severity, and category of the disability identified using the two determination
      tools were compared. In the DGDSS, the ICF-DDT consisted of four models
      comprising nine modules to determine the presence and the severity of the
      disability. The differences between models (modules) are the different
      combinations of World Health Organization Disability Assessment Schedule 2.0
      (WHODAS 2.0) and Scale of Body Functions and Structures. RESULTS: Compared with
      the D-DDT, more patients were determined to be disability-free when using the ICF
      DDT. Module 1-1 had the highest profoundly severe rate, and module 2-2 had the
      highest mild and moderate disability rates. Module 2-1 had the highest severe
      disability rate. Module 1-1 resulted in the smallest difference, and module 3-1
      resulted in the largest difference, compared with the D-DDT. Feedback from users
      suggested that the DGDSS is a robust system if the original data are accurate.
      CONCLUSION: The presence, severity, and category of the disability determined
      using the ICF-DDT and the D-DDT were significantly different. The results of the
      DGDSS provide information for policymakers to determine the optimal allocation of
      social welfare and medical resources for people with disabilities.

PMID- 23871552
TI  - An improved cellular automaton method to model multispecies biofilms.
AB  - Biomass-spreading rules used in previous cellular automaton methods to simulate
      multispecies biofilm introduced extensive mixing between different biomass
      species or resulted in spatially discontinuous biomass concentration and
      distribution; this caused results based on the cellular automaton methods to
      deviate from experimental results and those from the more computationally
      intensive continuous method. To overcome the problems, we propose new biomass
      spreading rules in this work: Excess biomass spreads by pushing a line of grid
      cells that are on the shortest path from the source grid cell to the destination
      grid cell, and the fractions of different biomass species in the grid cells on
      the path change due to the spreading. To evaluate the new rules, three two
      dimensional simulation examples are used to compare the biomass distribution
      computed using the continuous method and three cellular automaton methods, one
      based on the new rules and the other two based on rules presented in two previous
      studies. The relationship between the biomass species is syntrophic in one
      example and competitive in the other two examples. Simulation results generated
      using the cellular automaton method based on the new rules agree much better with
      the continuous method than do results using the other two cellular automaton
      methods. The new biomass-spreading rules are no more complex to implement than
      the existing rules. 

PMID- 23871553
TI  - Global survey of healthcare practitioners' beliefs and practices around
      intrauterine contraceptive method use in nulliparous women.
AB  - BACKGROUND: Despite the efficacy and safety of intrauterine contraceptive methods
      (IUCs), healthcare providers (HCPs) are sometimes reluctant to recommend their
      use, particularly in nulliparous women. This study sought to understand the
      global practitioner perceived impediments to IUC provision. STUDY DESIGN: We
      developed an online survey for HCPs administered across 4 regions comprising 15
      countries. We sought their attitudes to IUC provision; their perceived barriers
      to IUC use, particularly in nulliparous women; as well as their knowledge of the
      World Health Organization Medical Eligibility Criteria (WHO MEC) for
      contraceptive use. RESULTS: We received 1862 responses from HCPs in 15 countries
      grouped into 4 regions, with an average country response rate of 18%. For
      analysis, the results were grouped into these regions: Latin America, 402
      (21.6%); USA, 156 (8.4%); Europe and Canada, 1103 (59.2%); and Australia, 201
      (10.8%). The two most frequently identified perceived barriers to IUC use in
      nulliparous women were difficulty of insertion (56.6%) and pelvic inflammatory
      disease (PID) (49.2%), but responses differed by region and HCP type. Only 49.7%
      recognized the correct WHO MEC category for IUC use in nulliparous women.
      DISCUSSION: The results of this survey confirm that, across the four regions, the
      two main barriers to IUC provision for nulliparous women are concern about the
      difficulty of insertion and PID. Providers' knowledge of the WHO MEC was lacking
      universally. A global effort is required to improve understanding of the evidence
      and knowledge of available guidelines for IUC use.

PMID- 23871554
TI  - Congenital cystic adenomatous malformation (CCAM): remove or not, how can we
      progress?

PMID- 23871555
TI  - Should asymptomatic congenital cystic adenomatous malformations be removed? the
      case against.
AB  - In this article, we debate the pros and cons for the surgical removal of
      asymptomatic antenatally diagnosed cystic adenomatous malformations (CCAM). It is
      often argued that asymptomatic antenatally diagnosed CCAMs should be surgically
      removed in infancy due to the risk of future malignancy, future risk of infection
      and other symptoms and of increased risk of surgery after infective episodes.
      However, the risk of malignancy is often overplayed and the risk may not even be
      decreased after excision of the CCAM. Furthermore, the risk of future symptoms is
      uncertain thus surgical removal will subject many infants to unnecessary risk.
      Medical follow up will decrease the numbers that undergo surgical intervention
      and newer imaging techniques are likely to decrease the radiation risk. Whichever
      route of management is followed there is an urgent need to outline the natural
      history of asymptomatic CCAMs. 

PMID- 23871556
TI  - Theoretical analysis of wavefront aberration caused by treatment decentration and
      transition zone after custom myopic laser refractive surgery.
AB  - PURPOSE: To analyze the induced wavefront aberrations caused by treatment
      decentration and transition zone after custom myopic laser refractive surgery.
      SETTING: Refractive Surgery Center, Tianjin Eye Hospital & Eye Institute, Tianjin
      Medical University, Tianjin, China. DESIGN: Cohort study. METHODS: Wavefront
      aberration data from potential refractive surgery candidates were used. Based on
      the preoperative wavefront aberrations, the custom ablation profile was computed.
      Then, the influence of treatment decentration and especially that of the
      transition zone on induced wavefront aberrations was studied. The impact of angle
      mismatch on induced aberrations was analyzed. RESULTS: Data from 117 eyes (77
      patients) were analyzed. The transition zone played a significant role in the
      influence of decentration on the induced aberrations in refractive surgery.
      Induced coma and spherical aberration increased rapidly as the lateral
      translation increased, and coma was significantly larger than other Zernike
      aberration terms. The induced aberrations from decentration with oblique
      incidence in the laser ablation profile were less than in the actual laser
      ablation process for slight subclinical decentration. The induced aberrations
      were not closely related to the subclinical unmatched angle from eye
      cyclotorsion. The induced aberrations from lateral translation were correlated
      with the position vector. The transition zone was designed to smooth the
      transition from the optical zone to the untreated cornea, and it mainly dominated
      induced coma and spherical aberration. CONCLUSION: To achieve the best
      postoperative visual performance, the effect of the transition zone in refractive
      surgery should be taken into account, especially for scotopic pupils.

PMID- 23871557
TI  - A validated procedure for detection and quantitation of salvinorin a in
      pericardial fluid, vitreous humor, whole blood and plasma using solid phase
      extraction and gas chromatography-mass spectrometry.
AB  - The use of vitreous humor and pericardial fluid as alternative matrices to blood
      and plasma in the field of forensic toxicology is described to quantitate low
      levels of Salvinorin A using ethion as internal standard. The method was
      optimized and fully validated using international accepted guidelines. The
      developed methodology utilizes a solid phase extraction procedure coupled to gas
      chromatography mass spectrometry operated in the selected ion monitoring mode.
      The method was linear in the range of 5.0-100ng/mL with determination
      coefficients higher than 0.99 in 100MUL of vitreous humor and in 250MUL of each
      matrix pericardial fluid, whole blood and plasma. The limits of detection and
      quantitation were experimentally determined as 5.0ng/mL, intra-day precision,
      intermediate precision and accuracy were in conformity with the criteria normally
      accepted in bioanalytical method validation. The sample cleanup step presented
      mean efficiencies between 80 and 106% in the different biological specimens
      analyzed. According to the low volumes of samples used, and the low limits
      achieved using a single quadrupole mass spectrometer, which is available in most
      laboratories, we can conclude that the validated methodology is sensitive and
      simple and is suitable for the application in forensic toxicology laboratories
      for the routine analysis of Salvinorin A in both conventional and unconventional
      biological samples. 

PMID- 23871558
TI  - Preparation of a polyhedral oligomeric silsesquioxane-based perfluorinated
      monolithic column.
AB  - A monolithic column with high affinity to fluorous compounds was prepared using a
      polyhedral oligomeric silsesquioxane (POSS) reagent as the cross-linker and
      pentadecafluorooctyl methacrylate (PDFOMA) as the functionality monomer. The pore
      properties and permeability could be tuned by the composition of the
      polymerization mixture. The characterization and evaluation results revealed that
      the obtained POSS-PDFOMA hybrid monolith owned the merits of POSS and PDFOMA with
      good mechanical stability, no residual silanol and high affinity to fluorous
      compounds. A series of perfluoroalkyl methacrylates were baseline resolved on the
      optimized monolithic column under isocratic elution of 70% acetonitrile aqueous
      solution. Such a resolution could not be achieved on a silica-based C18
      monolithic column. A column efficiency of 30000N/m was observed. In addition,
      several perfluoroalkyl sulfonates were also baseline separated on the fluorous
      monolith applying 0.1% (v/v) acetic acid aqueous solution containing 75%
      acetonitrile as mobile phase without the addition of ammonium. 

PMID- 23871559
TI  - Determination of pesticide residues in high oil vegetal commodities by using
      various multi-residue methods and clean-ups followed by liquid chromatography
      tandem mass spectrometry.
AB  - Several extraction methods were evaluated in terms of recoveries and extraction
      precision for 113 pesticides in avocado: QuEChERS with various d-SPE clean-ups (Z
      Sep, Z-Sep+, PSA+C18 and silica), miniLuke and ethyl acetate. Extracts were
      analysed using liquid chromatography coupled with triple quadrupole mass
      spectrometer working in multi-reaction monitoring mode. Z-Sep and Z-Sep+ are new
      types of material for high lipid matrices - these two sorbents contain ZrO2,
      which improves fat removal from the extracts. The QuEChERS protocol with Z-Sep
      provided the highest number of pesticides with recoveries in the 70-120% range
      along with the lowest amount of coextracted matrix compounds. Subsequently, this
      method was validated in two matrices - avocado and almonds. In the validation
      recoveries at two levels - 10 and 50MUg/kg - limit of quantitation, linearity,
      matrix effects, as well as the inter- and intraday precision were studied. In the
      avocado samples, 107 analytes had LOQs equal to 10MUg/kg (signal to noise of
      quantitative transition was equal 20 or more). In the almond samples, 92
      pesticides had LOQs equal to 10MUg/kg (S/N>=20) and 2 pesticides at 50MUg/kg. The
      validated method was employed in the analysis of real avocado and almond samples.

PMID- 23871560
TI  - Rapid solid-phase extraction and analysis of resveratrol and other polyphenols in
      red wine.
AB  - Red wine has long been credited as a good source of health-beneficial
      antioxidants, including the bioactive polyphenols catechin, quercetin, and (E)
      resveratrol. In this paper, we report the application of reusable molecularly
      imprinted polymers (MIPs) for the selective and robust solid-phase extraction
      (SPE) and rapid analysis of (E)-resveratrol (LOD=8.87*10(-3) mg/L, LOQ=2.94*10(
      2) mg/L), along with a range of other polyphenols from an Australian Pinot noir
      red wine. Optimization of the molecularly imprinted solid-phase extraction
      (MISPE) protocol resulted in the significant enrichment of (E)-resveratrol and
      several structurally related polyphenols. These secondary metabolites were
      subsequently identified by RP-HPLC and MULC-ESI ion trap MS/MS methods. The
      developed MISPE protocol employed low volumes of environmentally benign solvents
      selected according to the Green Chemistry principles, and resulted in the
      recovery of 99% of the total (E)-resveratrol present. These results further
      demonstrate the potential of generic protocols for the analysis of target
      compound with health beneficial properties within the food and nutraceutical
      industries using tailor-made MIPs.

PMID- 23871561
TI  - In-vial dual extraction liquid chromatography coupled to mass spectrometry
      applied to streptozotocin-treated diabetic rats. Tips and pitfalls of the method.
AB  - The aim of metabolomics studies is the comprehensive and quantitative analysis of
      all metabolites in a cell, tissue or organism. This approach requires sample
      preparation methods to be fast, reproducible and able to extract a wide range of
      analytes with different polarities, as well as analytical platforms able to
      detect the extracted metabolites. Recently, we have developed a one-step
      extraction method consisting of a lipophilic and hydrophilic layer within a
      single vial insert, in-vial dual extraction (IVDE). In order to check possible
      application of this method to real biological case, analysis of plasma samples
      obtained from three streptozotocin-induced diabetic and three control rats was
      performed. Analytical validity of the method was proved by the calculation (in
      quality control samples) of relative standard deviation (RSD) for detected
      metabolites. The percentage of metabolites with RSD<30% was 93% for Fatty acyls,
      80% for Glycerolipids, 93% for Glycerophospholipids, 68% for Sterol lipids, and
      91% for Sphingolipids. IVDE allowed for selection of more than 600 different
      features discriminating two studied groups. For around 40% of these masses
      putative identification was possible. Adequate, with several considerations
      described within this paper, application of IVDE method enables wide metabolite
      coverage from a single 20MUL plasma aliquot. Within the features putatively
      identified, glycerolipids and glycerophospholipids arose as the most important
      groups of compounds discriminating diabetic rats from controls. All
      discriminating metabolites give an idea of the large metabolic differences that
      can be present in non-controlled type 1 diabetes. 

PMID- 23871562
TI  - Optimized liquid chromatography tandem mass spectrometry approach for the
      determination of diquat and paraquat herbicides.
AB  - Liquid chromatography tandem mass spectrometry (LC-MS/MS) determination of
      quaternary ammonium herbicides diquat (DQ) and paraquat (PQ) can be very
      challenging due to their complicated chromatographic and mass spectrometric
      behaviors. Various multiple reaction monitoring (MRM) transitions from radical
      cations M(+) and singly charged cations [M-H](+), have been reported for LC-MS/MS
      quantitation under different chromatographic and mass spectrometric conditions.
      However, interference peaks were observed for certain previously reported MRM
      transitions in our study. Using a Dionex Acclaim((r)) reversed-phase and HILIC
      mixed-mode LC column, we evaluated the most sensitive MRM transitions from three
      types of quasi-molecular ions of DQ and PQ, elucidated the cross-interference
      phenomena, and demonstrated that the rarely mentioned MRM transitions from
      dications M(2+) offered the best selectivity for LC-MS/MS analysis. Experimental
      parameters, such as IonSpray (IS) voltage, source temperature, declustering
      potential (DP), column oven temperature, collision energy (CE), acid and salt
      concentrations in the mobile phases were also optimized and an uncommon
      electrospray ionization (ESI) capillary voltage of 1000V achieved the highest
      sensitivity. Employing the proposed dication transitions 92/84.5 for DQ and
      93/171 for PQ, the direct aqueous injection LC-MS/MS method developed was able to
      provide a method detection limit (MDL) of 0.1MUg/L for the determination of these
      two herbicides in drinking water. 

PMID- 23871563
TI  - Simultaneous analysis of aflatoxins B1, B2, G1, G2, M1 and ochratoxin A in breast
      milk by high-performance liquid chromatography/fluorescence after liquid-liquid
      extraction with low temperature purification (LLE-LTP).
AB  - The aims of this study were to optimize and validate a methodology for the
      simultaneous analysis of aflatoxins B1, B2, G1, G2, M1 (AFB1, AFB2, AFG1, AFG2,
      AFM1) and ochratoxin A (OTA) in breast milk, and to analyze these mycotoxins in
      samples obtained from human milk banks in the Federal District, Brazil. The
      optimized analytical method was based on liquid-liquid extraction with low
      temperature purification (3.25mL of acidified acetonitrile+0.75mL of ethyl
      acetate), followed by analysis by high-performance liquid chromatography with
      fluorescence detector (HPLC/FLD) and a photochemical post-column reactor. Limits
      of quantification (LOQ) ranged from 0.005 to 0.03ng/mL, recoveries from 73 to
      99.5%, and relative standard deviations (RSD) from 1.8 to 17.3%. The LLE-LTP
      extraction method was shown to be simple and cost-effective, since no columns
      were needed for clean-up. Only 2 of the 224 breast milk samples analyzed were
      positive for the mycotoxins, both samples containing AFB2 at the LOQ level
      (0.005ng/mL). The identity of the mycotoxin detected was confirmed by liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS). This result
      indicates that infants who are fed with breast milk from the milk banks are not
      at risk from aflatoxin and ochratoxin exposure. 

PMID- 23871564
TI  - Rapid speciation and determination of vanadium compounds using ion-pair reversed
      phase ultra-high-performance liquid chromatography inductively coupled plasma
      sector field mass spectrometry.
AB  - Environmental vanadium contamination is a potential concern to public health, as
      evidenced by its place on the U.S. Environmental Protection Agency Drinking Water
      Contaminant Candidate List as a priority contaminant. Vanadium toxicity varies
      significantly between different oxidation states; therefore, it is crucial to be
      able to monitor the speciation of vanadium in environmental samples. In this
      study, a novel method is described that utilizes ion-pair reversed-phase ultra
      high-performance liquid chromatography with inductively coupled plasma-sector
      field mass spectrometry (IP-RP-UHPLC-ICP-SFMS) to separate vanadyl and vanadate
      ions and resolve a major polyatomic spectral interference ((35)Cl(16)O(+)) in
      less than a minute. Detection limits were obtained in the low ngL(-1) (part per
      trillion) range with linear calibrations across several orders of magnitude
      (50ngL(-1)-100MUgL(-1)). The mechanism of chromatographic retention was
      elucidated through investigation of the role of ethylenediaminetetraacetic acid,
      tetrabutylammonium ion and pH on elution. The optimized method was then applied
      to the speciation of vanadium in local lake water samples. 

PMID- 23871566
TI  - [Computer assisted orthognathic surgery: Condyle repositioning.]
AB  - Computer aided surgery has become a standard in many fields. It is rarely used in
      orthognathic surgery. Twenty years ago, we developed a navigation system adapted
      to this surgery, especially for mandibular condyle repositioning. The system has
      been improved along with technological progress. The authors of several clinical
      studies have validated this system. It is now routinely used in our department,
      because of its educational virtues among other assets.

PMID- 23871565
TI  - [Solitary fibrous tumor of the orbit: Possibly recurrent in the long-run].
AB  - Solitary fibrous tumor (SFT) is a rare etiology of progressive unilateral
      exophthalmia. The tumor is of mesenchymal origin and it is usually well defined.
      But recurrences can occur despite of complete surgical resection. Metastases have
      been observed. Tumors of the SFT spectrum are considered as benign or low-grade
      malignant. Histological features do not currently allow any prognosis. The most
      important prognostic factor is complete surgical resection. Craniofacial
      approaches provide a good view of the tumor extensions and orbital contents.
      Recurrent tumors must be surgically removed when possible. Complementary
      treatments have not proved effective. A very long-term follow-up is mandatory.

PMID- 23871567
TI  - Assessment of surface water in the vicinity of fertilizer factory using fish and
      plants.
AB  - The genotoxic and toxic potential of polluted surface water exposed to a
      fertilizer factory effluent was evaluated using assays with fish (Cyprinus
      carpio) and plant (Lemna minor) model organisms. Beside classical physicochemical
      parameters, the contents of fluorides, some heavy metals and polycyclic aromatic
      hydrocarbons were analyzed as well. Surface water caused inhibition of plant
      growth and decrease of photosynthetic pigment content. Regarding DNA damage and
      oxidative stress parameters, both fish and plants showed similar response to the
      surface water. In confirmation to biochemical markers, histopathological analysis
      of gill and liver tissues revealed a higher incidence of lesions in fish exposed
      to polluted surface water. Generally, results obtained by biological monitoring
      were mostly in agreement with chemical analysis of the surface water, although
      several discrepancies were observed which might be due to difference in
      sensitivity of model organisms or in experimental conditions (laboratory and
      field exposure). The results imply that conventional chemical analysis should be
      extended to genotoxicity/toxicity assays as measured biological effects and the
      potential health hazard cannot be predicted based on the physicochemical
      characteristics of water samples alone. 

PMID- 23871568
TI  - Microbial dynamics in acetate-enriched ballast water at different temperatures.
AB  - The spread of invasive species through ships' ballast water is considered as a
      major ecological threat to the world's oceans. For that reason, the International
      Maritime Organization (IMO) has set performance standards for ballast water
      discharge. Ballast water treatment systems have been developed that employ either
      UV-radiation or 'active substances' to reduce the concentration of living cells
      to below the IMOs standards. One such active substance is a chemical mixture
      known as Peraclean((r)) Ocean. The residual of Peraclean((r)) Ocean is acetate
      that might be present at high concentrations in discharged ballast water. In cold
      coastal waters the breakdown of acetate might be slow, causing a buildup of
      acetate concentrations in the water if regularly discharged by ships. To study
      the potential environmental impact, microbial dynamics and acetate degradation
      were measured in discharge water from a Peraclean((r)) Ocean treatment system in
      illuminated microcosms. In addition, microbial dynamics and acetate degradation
      were studied at -1, 4, 10, 15 and 25 degrees C in dark microcosms that simulated
      enclosed ballast water tanks. Acetate breakdown indeed occurred faster at higher
      temperatures. At 25 degrees C the highest bacteria growth, fastest nutrient and
      oxygen consumption and highest DOC reduction occurred. On the other hand, at -1
      degrees C bacterial growth was strongly delayed, only starting to increase after
      12 days. Furthermore, at 25 degrees C the acetate pool was not depleted, probably
      due to nutrient and oxygen limitation. This means that not all acetate will be
      broken down in ballast water tanks, even during long voyages in warm waters. In
      addition, at low temperatures acetate breakdown in ballast water tanks and in
      discharged water will be extremely slow. Therefore, regular discharge of acetate
      enriched ballast water in harbors and bays may cause eutrophication and changes
      in the microbial community, especially in colder regions. 

PMID- 23871569
TI  - Dermal autografts as a substitute for acellular dermal matrices (ADM) in tissue
      expander breast reconstruction: a prospective comparative study.
AB  - The use of acellular dermal matrix (ADM) in tissue expander breast reconstruction
      has several advantages but increased complications have been reported. Dermal
      autografts may offer a safer and more cost-effective alternative. The purpose of
      this prospective study was to compare the outcomes of tissue expander breast
      reconstruction using dermal autografts with ADM-assisted reconstruction. Patients
      undergoing tissue expander breast reconstruction with either ADM or dermal
      autografts were enrolled. Autografts were harvested from the lower abdomen. At
      each follow-up visit, patients were surveyed on a seven-point scale for scar and
      overall satisfaction. Biopsies taken at the time of device exchange were
      evaluated histologically with CD34 staining to assess tissue integration and
      vessel ingrowth. Expansion parameters, complications, procedural costs, and
      operative times were compared. Forty-eight patients were enrolled (76 breasts).
      Twenty-seven patients received ADM, and twenty-one patients received dermal
      autograft. Wound healing complications were significantly higher in the ADM group
      (14.8% versus 4.8%, p-value = 0.03), as were major complications (18.5% versus
      0%, p-value < 0.01). Histologic vessel counts in the autograft group averaged 21
      vessels/mm(2), compared to 7 vessels/mm(2) in the ADM group (p-value < 0.01).
      There was no difference between the two groups in scar satisfaction or overall
      satisfaction. Patients receiving dermal autograft had a lower incidence of major
      complications and delayed wound healing than patients who received ADM. Despite
      harvest time, the overall cost of the ADM-assisted expander placement was higher.
      Dermal autograft-assisted breast reconstruction offers many of the benefits of
      ADM, but with a lower cost and improved safety profile.

PMID- 23871570
TI  - The keystone flap alternative in posttraumatic lower-extremity reconstruction.

PMID- 23871572
TI  - High discordance rates between sub-areolar and peri-tumoural breast
      lymphoscintigraphy.
AB  - OBJECTIVE: To test the hypothesis that sub-areolar (SA) lymphoscintigraphy (LSG)
      identifies the same sentinel node as peri-tumoural (PT) injections. BACKGROUND:
      It is commonly believed that all LSG techniques will identify the same sentinel
      lymph nodes (SLN) draining the breast. Hybrid imaging technology (SPECT/CT)
      allows accurate identification of the exact location of SLNs. Using SPECT/CT SA
      and PT LSG techniques were compared. METHOD: In a multi-centre trial 39 patients
      sequentially underwent LSG (SA followed by PT) separated by 2-7 days. Patients
      were referred by 4 surgeons to 3 LSG centres, with standardization of isotope
      (99mTc-antimony sulfide colloid), LSG and SPECT/CT evaluation techniques. LSG
      were evaluated for SLN concordance and degree of discordance in the axilla and
      internal mammary nodes (IMN). RESULTS: 39 eligible patients, median age 62 years,
      were recruited. Successful axillary SLN mapping for SA and PT injection
      techniques was 87% and 95% respectively. Successful internal mammary SLN mapping
      occurred with SA and PT LSG in 5% and 36% respectively. Discordance was
      identified in the IMN (39%) and axilla (21%), with an overall rate of discordance
      between SA and PT LSG of 56%. CONCLUSIONS: There is a high level of discordance
      in the localization of SLN by these commonly used LSG injection techniques. This
      discordance has implications for accuracy of axillary and extra-axillary staging
      and could impact on patient outcome.

PMID- 23871571
TI  - Arterial stiffness evaluation by cardio-ankle vascular index in hypertension and
      diabetes mellitus subjects.
AB  - Arterial stiffness is an independent predictor for vascular diseases. Cardio
      ankle vascular index (CAVI) is a new index of arterial stiffness. In the present
      study, we investigated the possible risk factors involving CAVI in hypertension
      and diabetes mellitus (DM) subjects. One thousand sixty-three subjects (M/F
      533/530) from Shougang Corporation Examination Center were divided into four
      groups: healthy group (n = 639); hypertension group (n = 312); DM group (n = 58);
      and hypertension with DM group (n = 54). CAVI was measured by VS-1000 apparatus.
      Our results showed that CAVI was significantly higher in hypertension subjects
      with DM than in healthy and hypertension group, respectively (8.59 +/- 1.08 vs
      7.23 +/- 1.10; 8.59 +/- 1.08 vs 7.94 +/- 1.33; both P < .05). CAVI was positively
      correlated with age, systolic blood pressure, diastolic blood pressure, pulse
      pressure, fasting plasma glucose, HbA1c, uric acid, total cholesterol,
      triglycerides in the entire group (r = 0.633, 0.280, 0.172, 0.269, 0.209, 0.254,
      0.176, 0.129, 0.175; all P < .05, respectively). There was negatively correlation
      between CAVI and high-density lipoprotein cholesterol in the entire group (r = 
      0.167; P < .05). Multivariate analysis showed that age, body mass index, HbA1c,
      and high-density lipoprotein cholesterol were independent associating factors of
      CAVI in all subjects (beta = 0.699; P < .001, beta = -0.189; P = .001, beta =
      0.144; P = .015, beta = -0.136; P = .019, respectively). Our present study
      suggested that CAVI was significantly higher in hypertension subjects with DM
      compared with healthy and hypertension groups. 

PMID- 23871574
TI  - Increased risk of suicidal ideation in Korean adults with both diabetes and
      depression.
AB  - We investigated the association between suicidal ideation and diabetes in Korean
      adults with and without depression. Diabetes is a significant risk factor for
      suicidal ideation and the coexistence of diabetes and depression was associated
      with a much higher risk of suicidal ideation than with diabetes alone. 

PMID- 23871573
TI  - The Dutch surgical colorectal audit.
AB  - INTRODUCTION: In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was
      initiated by the Association of Surgeons of the Netherlands (ASN) to monitor,
      evaluate and improve colorectal cancer care. The DSCA is currently widely used as
      a blueprint for the initiation of other audits, coordinated by the Dutch
      Institute for Clinical Auditing (DICA). This article illustrates key elements of
      the DSCA and results of three years of auditing. METHODS: Key elements include: a
      leading role of the professional association with integration of the audit in the
      national quality assurance policy; web-based registration by medical specialists;
      weekly updated online feedback to participants; annual external data verification
      with other data sources; improvement projects. RESULTS: In two years, all Dutch
      hospitals participated in the audit. Case-ascertainment was 92% in 2010 and 95%
      in 2011. External data verification by comparison with the Netherlands Cancer
      Registry (NCR) showed high concordance of data items. Within three years,
      guideline compliance for diagnostics, preoperative multidisciplinary meetings and
      standardised reporting increased; complication-, re-intervention and
      postoperative mortality rates decreased significantly. DISCUSSION: The success of
      the DSCA is the result of effective surgical collaboration. The leading role of
      the ASN in conducting the audit resulted in full participation of all colorectal
      surgeons in the Netherlands. By integrating the audit into the ASNs' quality
      assurance policy, it could be used to set national quality standards. Future
      challenges include reduction of administrative burden; expansion to a
      multidisciplinary registration; and addition of financial information and patient
      reported outcomes to the audit data.

PMID- 23871575
TI  - Morning pulse pressure is associated more strongly with elevated albuminuria than
      systolic blood pressure in patients with type 2 diabetes mellitus: post hoc
      analysis of a cross-sectional multicenter study.
AB  - AIMS: Recently, focus has been directed toward pulse pressure as a potentially
      independent risk factor for micro- and macrovascular disease. This study was
      designed to examine the relationship between pulse pressure taken at home and
      elevated albuminuria in patients with type 2 diabetes. METHODS: This study is a
      post hoc analysis of a cross-sectional multicenter study. Home blood pressure
      measurements were performed for 14 consecutive days in 858 patients with type 2
      diabetes. We investigated the relationship between systolic blood pressure or
      pulse pressure in the morning or in the evening and urinary albumin excretion
      using univariate and multivariate analyses. Furthermore, we measured area under
      the receiver-operating characteristic curve (AUC) to compare the ability to
      identify elevated albuminuria, defined as urinary albumin excretion equal to or
      more than 30 mg/g creatinine, of systolic blood pressure or pulse pressure.
      RESULTS: Morning systolic blood pressure (beta=0.339, P<0.001) and morning pulse
      pressure (beta=0.378, P<0.001) were significantly associated with logarithm of
      urinary albumin excretion independent of other potential co-factors. AUC for
      elevated albuminuria in morning systolic blood pressure and morning pulse
      pressure were 0.668 (0.632-0.705; P<0.001) and 0.694 (0.659-0.730; P<0.001),
      respectively. AUC of morning pulse pressure was significantly greater than that
      of morning systolic blood pressure (P=0.040). CONCLUSIONS: Our findings implicate
      that morning pulse pressure is associated with elevated albuminuria in patients
      with type 2 diabetes, which suggests that lowering morning pulse pressure could
      prevent the development and progression of diabetic nephropathy.

PMID- 23871576
TI  - Occurrence of 210Po in periwinkle (Littorina undulata, Gray, 1839) collected from
      Kudankulam (Gulf of Mannar (GOM), Southeast coast of India).
AB  - Polonium-210 activity concentration was analysed in the whole body tissue of
      periwinkle Littorina undulata collected from intertidal rocky shore along
      Kudankulam coast. We carried out the study for a period of 12 months (2011-2012)
      focusing on three seasons. (210)Po was found non-uniformly distributed among the
      periwinkles depending on the allometry. The (210)Po accumulation showed a
      significant difference between seasons (p<0.05). Smaller sized winkles registered
      higher activity of (210)Po compared to larger ones (p<0.05). The overall activity
      range of (210)Po varied from 13.5 to 58.9 Bq/kg (wet). The activity of (210)Po
      was also quantified in seawater and intertidal sediments to calculate the
      biological concentration factor (BCF) and radiation dose rate. The dose rate to
      the winkles was performed using ERICA Assessment Tool and it was within the
      prescribed limit. The intake of (210)Po through periwinkles delivered an
      effective dose in the range of 2.2-9.6 MUSv/y to human beings.

PMID- 23871577
TI  - Mercury and selenium biomagnification in a Brazilian coastal food web using
      nitrogen stable isotope analysis: a case study in an area under the influence of
      the Paraiba do Sul River plume.
AB  - Mercury (Hg), selenium (Se) and nitrogen (delta(15)N) stable isotope were
      assessed in a tropical food web of Rio de Janeiro's north coast. Isotopic data on
      muscle suggest a difference related to this parameter along the food web; where
      top-predators (cetacean and voracious fish) displayed heavier delta(15)N over the
      entire food web. Both top-predators presented similar delta(15)N values. Cetacean
      displayed higher Hg and lower Se than voracious fish. Five trophic positions (TP)
      were found in relation to primary consumer as baseline, ranging from 2.0 to 4.0.
      Positive relationships were found between trace-element and delta(15)N. The slope
      of regression equations (0.11 for Se and 0.21 for Hg) and food web magnification
      factors (2.4 for Se and 5.4 for Hg) showed that Hg presented higher rate of
      increase over the food web. Simultaneous measurements of trace-elements and
      ecological tracers emphasize the importance of TP into the trophic structure and
      distribution of Hg and Se throughout the food web. 

PMID- 23871578
TI  - Temporal evolution of lead isotope ratios in sediments of the Central Portuguese
      Margin: a fingerprint of human activities.
AB  - Stable Pb isotope ratios ((206)Pb/(207)Pb, (208)Pb/(206)Pb), (210)Pb, Pb, Al, Ca,
      Fe, Mn and Si concentrations were measured in 7 sediment cores from the west
      coast of the Iberian Peninsula to assess the Pb contamination throughout the last
      200 years. Independently of their locations, all cores are characterized by
      increasing Pb/Al rends not related to grain-size changes. Conversely, decreasing
      trends of (206)Pb/(207)Pb were found towards the present. This tendency suggest a
      change in Pb sources reflecting an increased proportion derived from
      anthropogenic activities. The highest anthropogenic Pb inventories for sediments
      younger than 1950s were found in the two shallowest cores of Cascais and Lisboa
      submarine canyons, reflecting the proximity of the Tagus estuary. Lead isotope
      signatures also help demonstrate that sediments contaminated with Pb are not
      constrained to estuarine-coastal areas and upper parts of submarine canyons, but
      are also to transferred to a lesser extent to deeper parts of the Portuguese
      Margin.

PMID- 23871579
TI  - Anthropogenic input of heavy metals in two Audouin's gull breeding colonies.
AB  - Anthropogenic activities have become an important source of heavy metals to the
      marine environments. Biological sentinels like seabirds' chicks have been widely
      used to monitorize the levels of some heavy metals. Due to its mainly marine
      foraging habits, Audouin's gull fits well for this purpose. Mercury and lead
      levels were measured in mantle feathers of Audouin's gull chicks from two
      colonies in NE Iberian Peninsula: the Ebro Delta and the Llobregat Delta. Both
      are anthropized areas subject to differential pollutant inputs. Lead levels were
      significantly higher in the Llobregat Delta probably due to the use of leaded
      fuel in the nearby Barcelona airport. On the other side, mercury concentrations
      were higher in the Ebro Delta, in relation with the disposal of the toxic
      sediments at the Flix site carried down by the Ebro River. These mercury levels
      in the Ebro chicks reached values that have been described as toxic. 

PMID- 23871580
TI  - Effects of suspended particles on the growth of two dominant phytoplankton
      species of Bohai Bay, China.
AB  - Suspended particles (SP) are increasing dramatically in Bohai Bay, China and may
      affect the growth and composition of phytoplankton assembly. To determine the
      effects of SP on the growth of two dominant phytoplankton species, Phaeodactylum
      tricornutum Bohlin and Gymnodinium sp., we cultured and tested their growth
      characteristics under SP concentrations ranging from 0 g L(-1) to 0.8 g L(-1).
      Our results show that the increase in the SP concentrations results in
      significant decrease in the maximum cell densities and the maximum specific
      growth rates of these two species. The half maximal inhibitory concentration
      (IC50) of SP to P. tricornutum and Gymnodinium sp. were 1.07 g L(-1) and 0.68 g
      L(-1) respectively, indicating the inhibitory effect of SP on Gymnodinium sp. was
      greater than on P. tricornutum. These results suggest that SP inhibits the growth
      of the two algal species and P. tricornutum is more tolerant to SP than
      Gymnodinium sp.

PMID- 23871581
TI  - An experience with plasma exchange treatment of acute lymphoblastic leukemia in a
      case with fulminant hepatitis related to L-asparaginase.
AB  - Acute lymphoblastic leukemia (ALL) is a malignant disorder resulting from the
      clonal proliferation of lymphoid precursors with arrested maturation. L
      asparaginase is commonly used in combination chemotherapy of both pediatric and
      adult acute lymphoblastic leukemias. The most commonly encountered side effects
      of L-asparaginase are hypersensitivity reactions like pyrexia, urticaria, skin
      rash, and respiratory distress. There are also other side effects like
      anaphylaxis, coagulopathy, pancreatitis, thrombosis, and hepatic toxicity.
      Plasmapheresis can sometimes be appropriate to manage an overdose of drugs that
      circulate in the plasma compartment. We have reported plasmapheresis treatment of
      fulminant hepatitis in a patient with ALL after L-asparaginase treatment.

PMID- 23871582
TI  - Results of a preoperative autologous blood donation program for patients
      undergoing elective major spine surgery.
AB  - BACKGROUND AND OBJECTIVES: Spinal surgery has been shown to have a high blood
      transfusion requirement. Preoperative autologous blood donation (PABD) is a
      strategy to reduce the allogeneic transfusions in this subset of patients.
      MATERIAL AND METHODS: We retrospectively reviewed transfusion outcome of patients
      undergoing elective major spinal surgery from 2005 to 2011, and included in the
      PABD program. Transfusion outcome was compared with a group of patients that did
      not enter in the program during the same period. RESULTS: A total of 148 patients
      were included in the program during the analyzed period. Patients in the PABD
      program benefited from reduced exposure to allogeneic blood (Odds Ratio: 0.077,
      95% confidence interval 0.043-0.140). However, 12.16% (n=18) of these patients
      received also allogeneic blood (total 40 red blood cell units). Univariate
      analysis showed the following parameters as significantly predictors of
      transfusion: inclusion in the program (p<0.000), number of levels fused (Odds
      Ratio: 1.143, p=0.010), and number of autologous red blood cells donated (Odds
      Ratio: 1.906, p<0.000). CONCLUSIONS: The preoperative autologous blood donation
      program designed in our hospital was effective for reducing allogeneic
      transfusion in mostly young patients under major elective spinal surgery. However
      and as expected, their inclusion in the program increased the risk to be
      transfused.

PMID- 23871583
TI  - Managing uncontrolled postsplenectomy reactive thrombocytosis in idiopathic
      thrombocytopenic purpura: role of thrombocytapheresis.
AB  - Reactive thrombocytosis occurs in response to infection, trauma, or surgery.
      Splenectomy alone accounts for 19% of all possible causes of extreme
      thrombocytosis. We performed thrombocytapheresis in a young lady with chronic
      idiopathic thrombocytopenic purpura (ITP) who developed postsplenectomy reactive
      thrombocytosis. Her post splenectomy platelet count was 227 * 10(6)/ml which
      elevated to 1623 * 10(6)/ml on the 7th postoperative day. A single
      thrombocytapheresis procedure reduced her platelet to 403 * 10(6)/ml. She was
      discharged on the 10th postoperative day and then maintained a count of 204-238 *
      10(6)/ml with aspirin. Thrombocytapheresis reduces the platelet count rapidly in
      thrombocytosis and prevents patients from having thrombotic events. However, such
      procedures should be performed very meticulously to ensure patient safety.

PMID- 23871584
TI  - Mimicking the endogenous current of injury improves post-infarct cardiac
      remodeling.
AB  - Myocardial ischemia/reperfusion and infarction (I/R/I) is a leading cause of
      morbidity and mortality worldwide. The development of effective interventions for
      I/R/I has had only limited success due to the complex pathological processes of
      primary and secondary injury that follow I/R/I. Primary injury consists of cell
      death induced by the ischemic insult. Secondary injury results from activation of
      inflammatory processes that can induce secondary damage by apoptosis, lipid
      peroxidation, oxidative stress, or free radical formation. Thus the inflammatory
      and reparative response, after I/R/I, involves a complex, tightly controlled, and
      regulated cascade of events that lead to a replacement of the necrotic tissue
      with a collagen-rich scar. Timely activation and suppression of the inflammatory
      cascade and regulation of the reparative process is critical to prevent excessive
      tissue degradation, infarct expansion and heart failure. Accordingly,
      interventions that physiologically adjust the delicate balance between the
      essential and detrimental facets of inflammation are expected to provide new
      therapeutic opportunities. In this context, injury currents are endogenous,
      physiological mechanisms by which electrical fields interact with the innate
      immune system to modulate and restrain the inflammatory cascade and promote the
      reparative process. Accordingly, application of low intensity direct current
      (LIDC), by placing electrodes directly on the heart, and mimicking the current of
      injury is expected to enhance the complex biological mechanism of wound healing. 

PMID- 23871585
TI  - Fetal reprogramming and senescence in hypoplastic left heart syndrome and in
      human pluripotent stem cells during cardiac differentiation.
AB  - Hypoplastic left heart syndrome (HLHS) is a severe cardiac malformation
      characterized by left ventricle (LV) hypoplasia and abnormal LV perfusion and
      oxygenation. We studied hypoxia-associated injury in fetal HLHS and human
      pluripotent stem cells during cardiac differentiation to assess the effect of
      microenvironmental perturbations on fetal cardiac reprogramming. We studied LV
      myocardial samples from 32 HLHS and 17 structurally normal midgestation fetuses.
      Compared with controls, the LV in fetal HLHS samples had higher nuclear
      expression of hypoxia-inducible factor-1alpha but lower angiogenic growth factor
      expression, higher expression of oncogenes and transforming growth factor (TGF)
      beta1, more DNA damage and senescence with cell cycle arrest, fewer cardiac
      progenitors, myocytes and endothelial lineages, and increased myofibroblast
      population (P < 0.05 versus controls). Smooth muscle cells (SMCs) had less DNA
      damage compared with endothelial cells and myocytes. We recapitulated the fetal
      phenotype by subjecting human pluripotent stem cells to hypoxia during cardiac
      differentiation. DNA damage was prevented by treatment with a TGF-beta1 inhibitor
      (P < 0.05 versus nonhypoxic cells). The hypoplastic LV in fetal HLHS samples
      demonstrates hypoxia-inducible factor-1alpha up-regulation, oncogene-associated
      cellular senescence, TGF-beta1-associated fibrosis and impaired vasculogenesis.
      The phenotype is recapitulated by subjecting human pluripotent stem cells to
      hypoxia during cardiac differentiation and rescued by inhibition of TGF-beta1.
      This finding suggests that hypoxia may reprogram the immature heart and affect
      differentiation and development. 

PMID- 23871586
TI  - How is the awareness of the medical community about "evidence-based practice"?

PMID- 23871587
TI  - Caregiver strain in Parkinson's disease: national Parkinson Foundation Quality
      Initiative study.
AB  - BACKGROUND: National Parkinson Foundation Quality Improvement Initiatives (NPF
      QII) is the first large scale data-driven initiative in Parkinson's disease (PD)
      aimed at identifying variables predicting best care models and outcomes.
      OBJECTIVE: To determine what measures of PD disability, demographics, and patient
      quality of life are associated with caregiver strain among caregivers of patients
      with PD. METHODS: All PD patients at 18 participating sites are eligible for
      enrollment into the NPF-QII registry. Dataset includes multidimensional measures
      of disease severity, health care utilization, PD quality of life questionnaire-39
      (PDQ-39) and multidimensional caregiver strain inventory (MCSI). A univariate as
      well as an adjusted analysis was performed to examine the relationship between
      caregiver strain and variables of PD disability. RESULTS: The single best factor
      associated with high caregiver strain was the PDQ-39 total score (c-statistic of
      continuous variable = 0.792, p < 0.001) followed by the PDQ-mobility subscore (c
      = 0.776, p < 0.001). PDQ-39 >= 47 was the optimal cut off associated with a high
      caregiver strain with a sensitivity = 83% and specificity = 64%. A multiple
      logistic regression model with stepwise selection showed that in addition to PDQ
      39 >= 47 (OR and 95% confidence interval = 5.1 (3.2, 8.2), the following subject
      characteristics were associated with high caregiver strain: (model p < 0.001, c =
      0.838): Hoehn and Yahr stage >3 (2.0 (1.3, 3.1)), presence of concomitant
      medications such as antidepressants (2.1 (1.5, 3.1)) and antipsychotics (2.5
      (1.5, 4.2)), social worker visits (1.6 (1.2, 2.1)), male gender (2.3 (1.5, 3.5)),
      and decreased verbal fluency (0.95 (0.92, 0.98)). CONCLUSIONS: There is a high
      prevalence of caregiver strain in PD. PDQ-39 total score has the strongest
      association with high levels of caregiver strain. These results could guide
      clinicians in the assessment of caregivers at risk.

PMID- 23871588
TI  - MicroRNA-29b regulation of abdominal aortic aneurysm development.
AB  - Tremendous efforts have been initiated to elucidate the molecular and
      pathophysiological characteristics of abdominal aortic aneurysm (AAA) disease,
      which is a significant contributor to morbidity and mortality in the Western
      world. Recently, a novel class of small noncoding RNAs, called microRNAs, was
      identified as important transcriptional and posttranscriptional inhibitors of
      gene expression thought to simultaneously "fine tune" the translational output of
      multiple target messenger RNAs (mRNAs) by promoting mRNA degradation or
      inhibiting translation. Several research groups were able to identify the miR-29
      family, and miR-29b in particular, as crucial regulators of-not only vascular
      fibrosis-but also cardiac-, kidney-, liver-, and skin-fibrosis. The current
      review briefly points out data indicating a causal role for miR-29 in various
      diseases, while focusing on its potential benefit during AAA initiation and
      propagation. 

PMID- 23871590
TI  - Oscillation and polarity of E-cadherin asymmetries control actomyosin flow
      patterns during morphogenesis.
AB  - Actomyosin flows are involved in a variety of cellular processes, including
      cytokinesis, cell migration, polarization, and morphogenesis. In epithelia, flow
      polarization orients cell deformations. It is unclear, however, how flows are
      polarized and how global patterns of junction remodeling emerge from flow
      polarization locally. We address this question during intercalation-driving
      extension of the Drosophila germband. Intercalation is associated with polarized
      junction remodeling, whereby actomyosin pulses flow anisotropically toward dorsal
      ventral junctions and shrink them. Here, we show that planar polarization of
      flows emerges from polarized fluctuations in the levels of E-cadherin clusters
      that produce transient and oscillating asymmetries of coupling. These
      fluctuations are triggered by polarized E-cadherin endocytosis and are amplified
      by flow itself. This work suggests that fluctuations and mechanical instability
      are not the consequences of limited control over the systems key parameters, but
      rather that they define the axis of symmetry breaking. 

PMID- 23871589
TI  - Molecular signatures of tissue-specific microvascular endothelial cell
      heterogeneity in organ maintenance and regeneration.
AB  - Microvascular endothelial cells (ECs) within different tissues are endowed with
      distinct but as yet unrecognized structural, phenotypic, and functional
      attributes. We devised EC purification, cultivation, profiling, and
      transplantation models that establish tissue-specific molecular libraries of ECs
      devoid of lymphatic ECs or parenchymal cells. These libraries identify attributes
      that confer ECs with their organotypic features. We show that clusters of
      transcription factors, angiocrine growth factors, adhesion molecules, and
      chemokines are expressed in unique combinations by ECs of each organ.
      Furthermore, ECs respond distinctly in tissue regeneration models, hepatectomy,
      and myeloablation. To test the data set, we developed a transplantation model
      that employs generic ECs differentiated from embryonic stem cells. Transplanted
      generic ECs engraft into regenerating tissues and acquire features of organotypic
      ECs. Collectively, we demonstrate the utility of informational databases of ECs
      toward uncovering the extravascular and intrinsic signals that define EC
      heterogeneity. These factors could be exploited therapeutically to engineer
      tissue-specific ECs for regeneration. 

PMID- 23871591
TI  - Arsenic stabilization by zero-valent iron, bauxite residue, and zeolite at a
      contaminated site planting Panax notoginseng.
AB  - Panax notoginseng (Burk.) F.H. Chen, a rare traditional Chinese medicinal herb,
      is a widely used phytomedicine used all over the world. In recent years, the
      arsenic contamination of the herb and its relative products becomes a serious
      problem due to elevated soil As concentration. This study aimed to evaluate the
      effects of different types and dosages of amendments on As stabilization in soil
      and its uptake by P. notoginseng. Results showed that comparing to control
      treatment, the As concentrations of P. notoginseng declined by 49-63%, 43-61% and
      52-66% in 0.25% zero-valent iron (Fe(0)), 0.5% bauxite residue, and 1% zeolite
      treatment, respectively; whereas the biomasses were elevated by 62-116%, 45-152%
      and 114-265%, respectively. The As(III) proportions of P. notoginseng increased
      by 8%, 9%, and 8%, and the transfer factors of As from root to shoot increased by
      37%, 42% and 84% in the optimal treatments of Fe(0), bauxite residue, and
      zeolite. For soil As, all the three amendments could transform the non
      specifically adsorbed As fraction to hydrous oxides Fe/Al fractions (by Fe(0) and
      red mud) or specifically adsorbed As fraction (by zeolite), therefore reduced the
      bioavailability of soil As. With a comprehensive consideration of stabilization
      efficiency, plant growth, environmental influence, and cost, Fe(0) appeared to be
      the best amendment, and zeolite could also be a good choice. In conclusion, this
      study was of significance in developing As contamination control in P.
      notoginseng planting areas, and even other areas for medicinal herb growing. 

PMID- 23871592
TI  - Mass balance of anti-influenza drugs discharged into the Yodo River system,
      Japan, under an influenza outbreak.
AB  - In February 2011, at the peak of an influenza outbreak, we performed a
      comprehensive analysis of the mass balances of four anti-influenza drugs
      oseltamivir (OS), oseltamivir carboxylate (OC), amantadine (AMN), and zanamivir
      (ZAN)-in the urban area of the Yodo River system. This area includes three main
      river catchments (the Katsura, Uji, and Kidzu Rivers) and is home to 12 million
      people, about 10% of Japan's population. Water was sampled at six main rivers and
      13 tributary sites and eight sewage treatment plants (STPs). We concluded that
      the STP effluents were the major sources of the anti-influenza drug load in the
      Yodo River system (68-94% of total mass fluxes). Extended measurement throughout
      the Yodo River system further showed only small fluctuations of the ratio of OS
      to OC from 0.2 to 0.3, suggesting that OS and its metabolite are environmentally
      stable. The results also clearly showed the importance of reducing the levels of
      anti-influenza drugs in the water environment by reducing their emission at STPs.

PMID- 23871593
TI  - Quality control for sampling of PCDD/PCDF emissions from open combustion sources.
AB  - Both long duration (>6h) and high temperature (up to 139 degrees C) sampling
      efforts were conducted using ambient air sampling methods to determine if either
      high volume throughput or higher than ambient air sampling temperatures resulted
      in loss of target polychlorinated dibenzodioxins/dibenzofurans (PCDDs/PCDFs) from
      a polyurethane foam (PUF) sorbent. Emissions from open burning of simulated
      military forward operating base waste were sampled using EPA Method TO-9A for 185
      min duration using a filter/PUF/PUF in series combination. After a 54 m(3) sample
      was collected, the sampler was removed from the combustion source and the second
      PUF was replaced with a fresh, clean PUF. An additional 6h of ambient air
      sampling (171 m(3)) was conducted and the second PUF was analyzed to determine if
      the PCDD/PCDF transferred from the filter and the first PUF. Less than 4.4% of
      the initial PCDD/PCDF was lost to the second PUF. To assess the potential for
      blow off of PCDD/PCDF analytes during open air sampling, the mobility of spiked
      mono- to hepta-PCDD/PCDF standards across a PUF sorbent was evaluated from
      ambient air temperatures to 145 degrees C with total volumes between 600 L and
      2400 L. Lower molecular weight compounds and higher flow amounts increased
      release of the spiked standards consistent with vapor pressure values. At 600 L
      total sampled volume, the release temperature for 1% of the tetra-CDD (the lowest
      chlorinated homologue with a toxic compound) was 87 degrees C; increasing the
      volume fourfold reduced this temperature to 73 degrees C.

PMID- 23871594
TI  - A probabilistic model for the carry-over of PCDD/Fs from feed to growing pigs.
AB  - When food producing animals are contaminated with PCDD/F congeners, information
      on the contaminant's concentration in the bodies of the animals at time of
      slaughter is needed for risk management purposes. We have developed a
      mathematical model for the kinetics of PCDD/Fs in growing pigs in case of
      contaminated feed fed for a limited duration of time. This model allows the
      prediction of concentrations in body fat. It considers absorption fractions of
      PCDD/Fs, clearance by metabolism, dilution by growth and excretion through fecal
      fat. The model parameters were calibrated by fitting the model to experimental
      data. On the basis of this toxicokinetic model a probabilistic model has been
      constructed. The probabilistic model handles the parameters with appropriate
      probability distributions and Monte-Carlo simulation technique, providing for
      realistic situations with many animals and a range of contaminations and feeding
      intervals. We applied the new model to describe the German dioxin incident of
      winter 2010/2011 and discuss its viability as decision tool. The approach
      demonstrated here is a showcase how a risk assessment in the case of contaminated
      feeding can be performed.

PMID- 23871595
TI  - NDL-PCBs in muscle of the European catfish (Silurus glanis): an alert from
      Italian rivers.
AB  - The non-dioxin-like polychlorinated biphenyls (NDL-PCBs) highly contribute to the
      PCB dietary intake of total PCBs. Most of the NDL-PCBs are assumed through
      ingestion of contaminated fish and fishery products. Therefore, it is important
      to quantify their presence in aquatic organisms to evaluate human risks
      associated with fish consumption. The European catfish is a top food-chain
      predator and is considered a reliable bio-monitoring tool reflecting the state of
      the environmental organic pollution. From 2006 to 2009, 54 European catfish were
      captured in four sites covering the area of the Po River (North Italy), and their
      muscles were analysed to determine the levels of 18 PCBs congeners. All samples
      presented detectable levels of 18 congeners and, on average, results showed an
      important presence of NDL-PCBs. The sum of the six congeners (28, 52, 101, 138,
      153, 180 IUPAC) was used as indicator of the total PCBs concentration. The 33% of
      the samples analysed exceeded the maximum levels of 125 ng g(-1) set by European
      regulations in fish. The values measured ranged from 19.7 to 1015.4 ng g(-1)
      (mean 135.6 +/- 149.8 ng g(-1)). The concentrations of NDL-PCBs were not related
      to fish weight or sex, while a significant variability was found among sites
      (p<0.05), according to the geographical location of many industrial activities in
      the catchment area of the Po River. PCB 153 and 138 were present in higher
      concentrations (40% and 30% respectively). We hypothesise that this is due to
      their high resistance to metabolic degradation.

PMID- 23871596
TI  - Fenton and Fenton-like oxidation of pesticide acetamiprid in water samples:
      kinetic study of the degradation and optimization using response surface
      methodology.
AB  - The aims of this study were (a) to evaluate the degradation of acetamiprid with
      the use of Fenton reaction, (b) to investigate the effect of different
      concentrations of H2O2 and Fe(2+), initial pH and various iron salts, on the
      degradation of acetamiprid and (c) to apply response surface methodology for the
      evaluation of degradation kinetics. The kinetic study revealed a two-stage
      process, described by pseudo- first and second order kinetics. Different
      H2O2:Fe(2+) molar ratios were examined for their effect on acetamiprid
      degradation kinetics. The ratio of 3 mg L(-1) Fe(2+): 40 mg L(-1) H2O2 was found
      to completely remove acetamiprid at less than 10 min. Degradation rate was faster
      at lower pH, with the optimal value at pH 2.9, while Mohr salt appeared to
      degrade acetamiprid faster. A central composite design was selected in order to
      observe the effects of Fe(2+) and H2O2 initial concentration on acetamiprid
      degradation kinetics. A quadratic model fitted the experimental data, with
      satisfactory regression and fit. The most significant effect on the degradation
      of acetamiprid, was induced by ferrous iron concentration followed by H2O2.
      Optimization, aiming to minimize the applied ferrous concentration and the
      process time, proposed a ratio of 7.76 mg L(-1) Fe(II): 19.78 mg L(-1) H2O2. DOC
      is reduced much more slowly and requires more than 6h of processing for 50%
      degradation. The use to zero valent iron, demonstrated fast kinetic rates with
      acetamiprid degradation occurring in 10 min and effective DOC removal.

PMID- 23871597
TI  - The association between maternal nonylphenol exposure and parity on neonatal
      birth weight: a cohort study in Taiwan.
AB  - BACKGROUND: The aim of this study was to explore the association between NP
      exposure and parity and their effect on neonatal birth weight. METHODS: A cohort
      of pregnant women was established in a medical center in North Taiwan. Urinary NP
      concentration was determined by high-performance liquid chromatography coupled
      with fluorescent detection and adjusted using creatinine. A multivariable
      regression model was fit to determine the association between the maternal NP
      level in each trimester and neonatal birth weight. The odds ratios (ORs) of
      infant birth weight below the 10th, 25th, and 50th percentiles, comparing
      pregnant women with the different NP exposure levels, was estimated using a
      logistic regression. RESULTS: Of the 162 pregnant women in the study, 99 were
      multiparas and 63 were primiparas. After adjusting for other covariates, the NP
      level in the second trimester had a significant association with birth weight in
      the primiparas (beta = -182.49 g, p value = 0.02). The OR of low infant birth
      weight, comparing pregnant women with different NP levels, was increased by
      decreasing the cutoff percentile for birth weight (OR = 1.18 for the 50th
      percentile, 2.12 for the 25th percentile, and 7.81 for the 10th percentile). The
      odds of primiparas with high NP level having a low neonatal birth weight
      increased to 3.87, 11.77, and 9.40 for the three different percentiles (p value <
      0.05). CONCLUSION: Maternal NP exposure level is associated with an increased
      risk of low neonatal weight. Primiparas are especially at risk, and the second
      trimester of pregnancy may be the critical stage of exposure.

PMID- 23871599
TI  - Thermal properties and nanodispersion behavior of synthesized beta-sitosteryl
      acyl esters: a structure-activity relationship study.
AB  - The efficiency (dose response) of cholesterol-lowering effect of phytosterols in
      humans depends on their chemical forms (derived or non-derived) and formulation
      methods in a delivery system. With a series of synthesized beta-sitosteryl fatty
      acid esters (C2:0-C18:0 and C18:1-C18:3), this work examined their thermal
      properties and applications in preparation of nanodispersion with beta-sitosterol
      as a comparison. Inspection of the melting point (Tm) and the heat of fusion
      (DeltaH) of beta-sitosteryl fatty acid esters and the chain length and
      unsaturation degree of fatty acyl moiety revealed a pronounced structure-property
      relationship. The nanodispersions prepared with beta-sitosterol and beta
      sitosteryl saturated fatty acid (SFA) esters displayed different particle size
      distribution patterns (polymodal vs bimodal), mean diameter (115 nm vs less than
      100 nm), and polydispersity index (PDI) (0.50 vs 0.23-0.38). beta-sitosteryl
      unsaturated fatty acid (USFA) esters showed a distinctly different dispersion
      behavior to form nanoemulsions, rather than nanodispersions, with more
      homogeneous particle size distribution (monomodal, mean diameter 27-63 nm and PDI
      0.18-0.25). The nanodispersion of beta-sitosteryl medium chain SFA ester (C14:0)
      demonstrated a best storage stability.

PMID- 23871598
TI  - The ability of three different models of frailty to predict all-cause mortality:
      results from the European Male Aging Study (EMAS).
AB  - Few studies have directly compared the ability of the most commonly used models
      of frailty to predict mortality among community-dwelling individuals. Here, we
      used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to
      predict mortality in the EMAS. Participants were aged 40-79 years (n=2929) at
      baseline and 6.6% (n=193) died over a median 4.3 years of follow-up. The FI was
      generated from 39 deficits, including self-reported health, morbidities,
      functional performance and psychological assessments. The FP and FS consisted of
      five phenotypic criteria and both categorized individuals as robust when they had
      0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI
      increased linearly with age (r(2)=0.21) and in Cox regression models adjusted for
      age, center, smoking and partner status the hazard ratio (HR) for death for each
      unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP
      or FS definitions, had a significantly increased risk of death compared to their
      robust counterparts. Compared to robust men, those who were FP frail at baseline
      had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All
      three frailty models significantly predicted future mortality among community
      dwelling, middle-aged and older European men after adjusting for potential
      confounders. Our data suggest that the choice of frailty model may not be of
      paramount importance when predicting future risk of death, enabling flexibility
      in the approach used. 

PMID- 23871600
TI  - Quantitative nucleation and growth kinetics of gold nanoparticles via model
      assisted dynamic spectroscopic approach.
AB  - Lacking of quantitative experimental data and/or kinetic models that could
      mathematically depict the redox chemistry and the crystallization issue, bottom
      to-up formation kinetics of gold nanoparticles (GNPs) remains a challenge. We
      measured the dynamic regime of GNPs synthesized by l-ascorbic acid (representing
      a chemical approach) and/or foliar aqueous extract (a biogenic approach) via in
      situ spectroscopic characterization and established a redox-crystallization model
      which allows quantitative and separate parameterization of the nucleation and
      growth processes. The main results were simplified as the following aspects: (I)
      an efficient approach, i.e., the dynamic in situ spectroscopic characterization
      assisted with the redox-crystallization model, was established for quantitative
      analysis of the overall formation kinetics of GNPs in solution; (II) formation of
      GNPs by the chemical and the biogenic approaches experienced a slow nucleation
      stage followed by a growth stage which behaved as a mixed-order reaction, and
      different from the chemical approach, the biogenic method involved heterogeneous
      nucleation; (III) also, biosynthesis of flaky GNPs was a kinetic-controlled
      process favored by relatively slow redox chemistry; and (IV) though GNPs
      formation consists of two aspects, namely the redox chemistry and the
      crystallization issue, the latter was the rate-determining event that controls
      the dynamic regime of the whole physicochemical process. 

PMID- 23871601
TI  - Capacitive mixing for the extraction of energy from salinity differences: survey
      of experimental results and electrochemical models.
AB  - The "capacitive mixing" (CAPMIX) technique is an emerging technology aimed at the
      extraction of energy from salinity differences, e.g. between sea and river
      waters. CAPMIX benefits from the voltage rise that takes place between two
      electrodes dipped in a saline solution when its salt concentration is changed.
      Several kinds of electrodes have been proposed so far: activated carbon materials
      (Brogioli, 2009), membrane-based ion-selective electrodes (Sales et al., 2010),
      and battery electrodes (Biesheuvel and van der Wal, 2010). The power production
      mainly depends on two properties of each single electrode: the amplitude of the
      potential rise upon salinity change, and the potential in the high-salinity
      solution. The various electrode materials that have been used returned different
      values of the two parameters, and hence to different power productions. In this
      paper, we apply electrokinetic and electrochemical models to qualitatively
      explain the experimentally observed behaviors of various materials under
      different experimental conditions. The analysis allows to devise techniques for
      tailoring new materials, particularly suited for the CAPMIX technique. 

PMID- 23871602
TI  - Tuning of peptide assembly through force balance adjustment.
AB  - Controlled self-assembly of amphiphilic tripeptides into distinct nanostructures
      is achieved via a controlled design of the molecular architecture. The tripeptide
      Ac-Phe-Phe-Lys-CONH2 (FFK), hardly soluble in water, forms long amyloid-like
      tubular structures with the aid of beta-sheet hydrogen bonding and aromatic pi-pi
      stacking. Substitution of phenylalanine (F) with tyrosine (Y), that is, only a
      subtle structural variation in adding a hydroxyl group to the phenyl ring,
      results in great change in molecular self-assembly behavior. When one F is
      substituted with Y, the resulting molecules of FYK and YFK self-assemble into
      long thinner fibrils with high propensity for lateral association. When both Fs
      are substituted with Y, the resulting YYK molecule forms spherical aggregates.
      Introduction of hydroxyl groups into the molecule modifies aromatic interactions
      and introduces hydrogen bonding. Moreover, since the driving forces for peptide
      self-assembly including hydrogen bonding, electrostatic repulsion, and pi-pi
      stacking have high interdependence with each other, changes in aromatic
      interaction induce a Domino effect and cause a shift of force balance to a new
      state. This leads to significant variations in self-assembly behavior. 

PMID- 23871603
TI  - Thicker posterior insula is associated with disease duration in women with
      irritable bowel syndrome (IBS) whereas thicker orbitofrontal cortex predicts
      reduced pain inhibition in both IBS patients and controls.
AB  - Patients with irritable bowel syndrome (IBS) are affected by chronic abdominal
      pain and show decreased pain inhibition. Moreover, they exhibit differences in
      brain morphology compared with healthy volunteers. The aim of this study was to
      examine whether decreased pain inhibition is associated with altered brain
      morphology in IBS patients. Structural magnetic resonance imaging scans were
      acquired in 14 female patients with diarrhea-predominant IBS and 14 controls.
      Pain and anxiety modulation were characterized using electrical stimulation of
      the sural nerve and heterotopic noxious counterstimulation. IBS patients reported
      decreased pain inhibition (P = .02) as well as increased shock anxiety, pain
      catastrophizing, depressive symptoms, and trait anxiety (P's <= .05). IBS
      patients also showed a thicker right posterior insula (pINS), associated with
      longer IBS duration (r = .67, P = .02). In addition, thicker right lateral
      orbitofrontal cortex was strongly associated with less pain inhibition in both
      IBS patients (r = .70, P = .02) and controls (r = .68, P = .01). Results are
      consistent with the role of the insula in interoception and pain and suggest that
      IBS may induce thickening of the pINS. Reduced pain inhibition may further
      involve a modification of the regulatory influence of the orbitofrontal cortex on
      pain-related processes. PERSPECTIVE: This study investigated the brain morphology
      of IBS patients. IBS patients showed thicker right pINS, associated with longer
      disease duration but not with psychological symptoms. This suggests that IBS
      induces thickening of pINS, which may contribute to its pathophysiology,
      consistent with the role of the pINS in interoception and pain.

PMID- 23871604
TI  - A role for matrix metalloproteinases in regulating mammary stem cell function via
      the Wnt signaling pathway.
AB  - The microenvironment provides cues that control the behavior of epithelial stem
      and progenitor cells. Here, we identify matrix metalloproteinase-3 (MMP3) as a
      regulator of Wnt signaling and mammary stem cell (MaSC) activity. We show that
      MMP3 overexpression promotes hyperplastic epithelial growth, surprisingly, in a
      nonproteolytic manner via its hemopexin (HPX) domain. We demonstrate that MMP3
      HPX specifically binds and inactivates Wnt5b, a noncanonical Wnt ligand that
      inhibits canonical Wnt signaling and mammary epithelial outgrowth in vivo.
      Indeed, transplants overexpressing MMP3 display increased canonical Wnt
      signaling, demonstrating that MMP3 is an extracellular regulator of the Wnt
      signaling pathway. MMP3-deficient mice exhibit decreased MaSC populations and
      diminished mammary-reconstituting activity, whereas MMP3 overexpression elevates
      MaSC function, indicating that MMP3 is necessary for the maintenance of MaSCs.
      Our study reveals a mechanism by a microenvironmental protease that regulates Wnt
      signaling and impacts adult epithelial stem cell function. 

PMID- 23871606
TI  - Reprogramming of human fibroblasts to pluripotency with lineage specifiers.
AB  - Since the initial discovery that OCT4, SOX2, KLF4, and c-MYC overexpression
      sufficed for the induction of pluripotency in somatic cells, methodologies
      replacing the original factors have enhanced our understanding of the
      reprogramming process. However, unlike in mouse, OCT4 has not been replaced
      successfully during reprogramming of human cells. Here we report on a strategy to
      accomplish this replacement. Through a combination of transcriptome and
      bioinformatic analysis we have identified factors previously characterized as
      being lineage specifiers that are able to replace OCT4 and SOX2 in the
      reprogramming of human fibroblasts. Our results show that it is possible to
      replace OCT4 and SOX2 simultaneously with alternative lineage specifiers in the
      reprogramming of human cells. At a broader level, they also support a model in
      which counteracting lineage specification networks underlies the induction of
      pluripotency. 

PMID- 23871605
TI  - Reprogramming fibroblasts into bipotential hepatic stem cells by defined factors.
AB  - Recent studies have demonstrated direct reprogramming of fibroblasts into a range
      of somatic cell types, but to date stem or progenitor cells have only been
      reprogrammed for the blood and neuronal lineages. We previously reported
      generation of induced hepatocyte-like (iHep) cells by transduction of Gata4,
      Hnf1alpha, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs). Here, we
      show that Hnf1beta and Foxa3, liver organogenesis transcription factors, are
      sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs). iHepSCs
      can be stably expanded in vitro and possess the potential of bidirectional
      differentiation into both hepatocytic and cholangiocytic lineages. In the injured
      liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs
      become hepatocyte-like cells. They also engraft as cholangiocytes into bile ducts
      of mice with DDC-induced bile ductular injury. Lineage conversion into
      bipotential expandable iHepSCs provides a strategy to enable efficient derivation
      of both hepatocytes and cholangiocytes for use in disease modeling and tissue
      engineering. 

PMID- 23871607
TI  - [Neonatal collapse: diagnosis of myocarditis].
AB  - Enteroviruses are single-stranded RNA viruses of the picornavirus family. In the
      neonatal period, enterovirus can cause severe meningo-encephalitis, sepsis
      syndrome, hepatitis, or myocarditis. Neonatal enterovirus myocarditis remains a
      rare but severe cause of neonatal cardiac failure whose prognosis remains poor.
      Herein, we report the case of neonatal enterovirus myocarditis in a 14-day-old
      infant transferred to our intensive care unit for cardiogenic shock. Diagnosis
      and follow-up were confirmed using cardiac magnetic resonance imaging (MRI). We
      provide a detailed clinical, biological, and cardiac imaging description with
      specific comments on MRI diagnosis of myocarditis. 

PMID- 23871608
TI  - [Regulatory lymphocytes: a new cooperation between T and B cells for a better
      control of the immune response].
AB  - Mechanims of peripheral tolerance include molecular controls and the presence of
      regulatory lymphocytes. Regulatory T lymphocytes (Tregs) correspond to different
      sub-populations of T cells that control immune responses due to the production of
      cytokines, such as IL-10 and with direct cell-to-cell contacts. Tregs targets are
      antigen presenting cells, such as dendritic cells, effector CD4(+) and CD8(+)
      lymphocytes but also effector antibody-producing B lymphocytes. Regulatory B
      lymphocytes (Bregs) have been more recently described and likely represent
      different sub-populations of B cells that control the development of autoimmune
      and inflammatory diseases due to the production of IL-10 and using intercellular
      contacts. Bregs targets encompass all the cells involved in the immune responses
      which are thus under a dual control by regulatory lymphocytes. Development and
      efficient activity of Tregs appear dependent of Bregs for a better regulation of
      autoimmune reactions, of anti-infectious reactions, but also of anti-tumor
      reactions.

PMID- 23871609
TI  - Smad phospho-isoforms direct context-dependent TGF-beta signaling.
AB  - Better understanding of TGF-beta signaling has deepened our appreciation of
      normal epithelial cell homeostasis and its dysfunction in such human disorders as
      cancer and fibrosis. Smad proteins, which convey signals from TGF-beta receptors
      to the nucleus, possess intermediate linker regions connecting Mad homology
      domains. Membrane-bound, cytoplasmic, and nuclear protein kinases differentially
      phosphorylate Smad2 and Smad3 to create C-tail (C), the linker (L), or dually
      (L/C) phosphorylated (p, phospho-) isoforms. According to domain-specific
      phosphorylation, distinct transcriptional responses, and selective metabolism,
      Smad phospho-isoform pathways can be grouped into 4 types: cytostatic pSmad3C
      signaling, mitogenic pSmad3L (Ser-213) signaling, invasive/fibrogenic pSmad2L
      (Ser-245/250/255)/C or pSmad3L (Ser-204)/C signaling, and mitogenic/migratory
      pSmad2/3L (Thr-220/179)/C signaling. We outline how responses to TGF-beta change
      through the multiple Smad phospho-isoforms as normal epithelial cells mature from
      stem cells through progenitors to differentiated cells, and further reflect upon
      how constitutive Ras-activating mutants favor the Smad phospho-isoform pathway
      promoting tumor progression. Finally, clinical analyses of reversible Smad
      phospho-isoform signaling during human carcinogenesis could assess effectiveness
      of interventions aimed at reducing human cancer risk. Spatiotemporally separate,
      functionally different Smad phospho-isoforms have been identified in specific
      cells and tissues, answering long-standing questions about context-dependent TGF
      beta signaling. 

PMID- 23871610
TI  - Optogenetic cell control in experimental models of neurological disorders.
AB  - The complexity of the brain, in which different neuronal cell types are
      interspersed and complexly interconnected, has posed a major obstacle in
      identifying pathophysiological mechanisms underlying prevalent neurological
      disorders. This is largely based in the inability of classical experimental
      approaches to target defined neural populations at sufficient temporal and
      spatial resolution. As a consequence, effective clinical therapies for prevalent
      neurological disorders are largely lacking. Recently developed optogenetic probes
      are genetically expressed photosensitive ion channels and pumps that in principal
      overcome these limitations. Optogenetic probes allow millisecond resolution
      functional control over selected optogenetically transduced neuronal populations
      targeted based on promoter activity. This optical cell control scheme has already
      been applied to answer fundamental questions pertaining to neurological disorders
      by allowing researchers to experimentally intercept, or induce,
      pathophysiological neuronal signaling activity in a highly controlled manner.
      Offering high temporal resolution control over neural activity at high cellular
      specificity, optogenetic tools constitute a game changer in research aiming at
      understanding pathophysiological signaling mechanisms in neurological disorders
      and in developing therapeutic strategies to correct these. In this regard, recent
      experimental work has provided new insights in underlying mechanisms, as well as
      preliminary proof-of-principle for optogenetic therapies, of several neurological
      disorders, including Parkinson's disease, epilepsy and progressive blindness.
      This review synthesizes experimental work where optogenetic tools have been
      applied to explore pathologic neural network activity in models of neurological
      disorders. 

PMID- 23871611
TI  - Beyond the silence: bilateral somatosensory stimulation enhances skilled movement
      quality and neural density in intact behaving rats.
AB  - It is thought that a close dialogue between the primary motor (M1) and
      somatosensory (S1) cortices is necessary for skilled motor learning. The extent
      of the relative S1 contribution in producing skilled reaching movements, however,
      is still unclear. Here we used anodal transcranial direct current stimulation
      (tDCS), which is able to alter polarity-specific excitability in the S1, to
      facilitate skilled movement in intact behaving rats. We hypothesized that the
      critical role of S1 in reaching performance can be enhanced by bilateral tDCS.
      Pretrained rats were assigned to control or stimulation conditions: (1) UnAno:
      the unilateral application of an anodal current to the side contralateral to the
      paw preferred for reaching; (2) BiAno1: bilateral anodal current; (3) BiAno2: a
      bilateral anodal current with additional 30ms of 65MUA pulses every 5s. Rats
      received tDCS (65MUA; 10min/rat) to the S1 during skilled reach training for 20
      days (online-effect phase). After-effect assessment occurred for the next ten
      days in the absence of electrical stimulation. Quantitative and qualitative
      analyses of online-effects of tDCS showed that UnAno and BiAno1 somatosensory
      stimulation significantly improve skilled reaching performance. Bilateral BiAno1
      stimulation was associated with greater qualitative functional improvement than
      unilateral UnAno stimulation. tDCS-induced improvements were not observed in the
      after-effects phase. Quantitative cytoarchitectonic analysis revealed that
      somatosensory tDCS bilaterally increases cortical neural density. The findings
      emphasize the central role of bilateral somatosensory feedback in skill
      acquisition through modulation of cortico-motor excitability. 

PMID- 23871612
TI  - [Geophagy and pregnancy: current knowledge and management. Clinical experiences
      of an obstetrical department in French Guiana].
AB  - OBJECTIVE: To provide an overview of the current state of knowledge concerning
      the determinants and consequences of geophagy during pregnancy. METHOD:
      Bibliographic searching of articles published in English or French and included
      in the Scopus database, and reporting of our experience with the management of
      geophagic pregnant women at the maternity unit of Saint-Laurent-du-Maroni (French
      Guiana). RESULTS: Geophagy is a little known practice initiated by various
      stimuli, including nausea and iron deficiency. Sustained geophagy during
      pregnancy has many consequences, due to complex ionic interactions with the
      digestive tract. Clay consumption may lead to iron deficiency, which may even be
      life-threatening in cases of post-partum haemorrhage in severely anaemic women.
      For the foetus, in addition to the known risk of preterm birth associated with
      maternal anaemia, maternal geophagy may lead to overexposure to heavy metals,
      including aluminium in particular. This practice should therefore be considered
      potentially damaging to the neurological development of the child. The ionic
      imbalances caused by the ingestion of clay over a long period should be
      systematically evaluated and corrected, given the secondary malabsorption they
      may cause, often necessitating parenteral feeding.

PMID- 23871613
TI  - Visual vaccinology - the importance of visual communication.

PMID- 23871615
TI  - Stress-induced cardiomyopathy in the critically ill - why inotropes fail to
      improve outcome.

PMID- 23871614
TI  - Design questions for Streptococcus pneumoniae vaccine trials with a colonisation
      endpoint.
AB  - Evaluation of vaccine efficacy for protection against colonisation (VEcol) with
      Streptococcus pneumoniae and other bacterial pathogens is often based on a cross
      sectional study design, in which only one nasopharyngeal sample is obtained per
      study subject. Here we investigate the feasibility of this study design by
      investigating a number of practical design problems. Specific questions are
      related to the timing of colonisation measurement with respect to the time of
      vaccination, the adjustment for the within-host replacement of vaccine-type
      colonisation by the non-vaccine type pneumococci, and the impact of multiple
      serotype colonisation on VEcol estimation. We also discuss the issue of choosing
      the control vaccine, including comparison of two active pneumococcal vaccines, as
      well as the sample size and the statistical power of colonisation endpoint
      trials. In addition, the statistical design with the specific aim to include
      information about VEcol in the licensure process of new pneumococcal vaccine
      products is discussed. 

PMID- 23871616
TI  - A novel peptide inhibitor attenuates C-reactive protein's pro-inflammatory
      effects in-vivo.
AB  - BACKGROUND: Higher levels of C-reactive protein (CRP) predict cardiovascular
      events and also portend a poorer prognosis in patients with acute coronary
      syndromes. Much in-vitro and in-vivo data support a role for CRP in
      atherogenesis. METHODS: Using the one-bead-one-compound (OBOC) combinatorial
      library method we have successfully identified peptides against human CRP that
      inhibit its biological effects in-vitro. Hence we tested the effect of the best
      characterized inhibitor (CRP-i2) on the effects of CRP in an appropriate animal
      model, Wistar rats. RESULTS: Treatment with CRP resulted in significant increase
      in superoxide anion, nuclear factor kappaB (NFkappab) activity and the release of
      biomarkers of inflammation from macrophages compared to Wistar rats treated with
      human albumin (HuSA). Pre-treatment with the inhibitor, CRP-i2, resulted in a
      significant reduction in CRP induced superoxide anion, NFkappab activity and
      biomarkers of inflammation. Also, there were no observed clinical or laboratory
      related adverse effects. CONCLUSIONS: We demonstrate that our novel peptide
      inhibitor attenuates the proinflammatory effects of CRP in-vivo. Future studies
      will examine the long-term effects of this inhibitor on vascular pathobiology.

PMID- 23871617
TI  - MicroRNA associated with atherogenic dyslipidemia in South Asian men.

PMID- 23871618
TI  - beta-Blocker use in angiographic coronary artery disease patients without
      myocardial infarction or heart failure: a report from the ET-CHD registry, 1997
      2006.

PMID- 23871619
TI  - Cardiopulmonary exercise and 6-min walk tests as predictors of quality of life
      and long-term mortality among patients with heart failure due to Chagas disease.

PMID- 23871620
TI  - Heat shock protein inducer modifies arrhythmogenic substrate and inhibits atrial
      fibrillation in the failing heart.
AB  - BACKGROUND: Geranylgeranylacetone (GGA) has been reported up-regulating heat
      shock protein (HSP) expression, and protecting against atrial remodeling. This
      study aimed to investigate the effects of GGA on atrial electrophysiology and
      inducibility of atrial fibrillation (AF) in heart failure (HF) model. METHODS AND
      RESULTS: HF rabbits were created 4 weeks after coronary artery ligation.
      Monophasic action potential recordings and multielectrode array were used to
      record the electrophysiological characteristics of left atrium (LA) in normal, or
      HF rabbits with (HF-GGA) and without (HF-control) oral administration of GGA (200
      mg/kg, 24 h before experiments). The mRNA and protein expressions of ionic
      channels were measured by Western blot and PCR. HF-GGA LA (n = 10), similar to
      normal LA (n = 10) had a shorter action potential duration (APD) and effective
      refractory period than HF-control LA (n = 10). HF-GGA LA had less triggered
      activity and APD alternans (20% vs. 100%, P = 0.001), lower maxima slope of
      restitution curve of APD (0.94 +/- 0.04 vs.1.69 +/- 0.04, P < 0.001), and less
      inducibility of AF (50% vs. 100%, P = 0.033) than HF-control LA. HF-GGA LA had a
      shorter activation time and higher conduction velocity than HF-control LA. HF-GGA
      LA had a higher mRNA expression of Cav1.2, Nav1.5, Kir2.1, Kv1.4, Kv7.1, Kv11.1,
      sarcoplasmic reticulum Ca(2+)-ATPase, and higher phosphorylation of phospholamban
      than HF-control LA. CONCLUSIONS: GGA decreases triggered activity, dispersion of
      APD and inducibility of AF in failing heart through induction of HSP, and
      modulation of ionic channels and calcium homeostasis.

PMID- 23871621
TI  - Greek socio-economic crisis and incidence of acute myocardial infarction in
      Southwestern Peloponnese.

PMID- 23871622
TI  - A thirty-four-year-old chronic total occlusion successfully treated by
      percutaneous coronary intervention.

PMID- 23871623
TI  - Levosimendan reverted severe pulmonary hypertension in one patient on waiting
      list for heart transplantation.

PMID- 23871624
TI  - Idiopathic pericarditis presenting large hemorrhagic pericardial effusion.

PMID- 23871625
TI  - Compliance and persistence of free-combination antihypertensive therapy versus
      single-pill combination in Korean hypertensive patients.

PMID- 23871626
TI  - Polymorphic ventricular tachycardia after amiodarone infusion in extreme
      tachycardia-bradycardia-syndrome.

PMID- 23871627
TI  - Associated social factors of hypertension in adults and the very old: UK
      Understanding Society cohort, 2009-2010.

PMID- 23871628
TI  - Fulminant myocarditis: the role of cardiac magnetic resonance imaging.

PMID- 23871629
TI  - Pneumococcal pneumonia and the risk of acute coronary syndrome: a population
      based cohort study.

PMID- 23871630
TI  - Indication for percutaneous coronary intervention is not associated with symptoms
      of anxiety and depression.

PMID- 23871631
TI  - Current evidence and future perspectives on n-3 PUFAs.
AB  - The family of polyunsaturated fatty acids (PUFAs), which can be found in most
      lipid classes, includes n-3 PUFAs essential for mammals and whose deficiency is
      associated with multiple diseases. Because of their multiple physiological
      actions, n-3 PUFAs play a crucial role in normal human metabolism as well as
      maintenance of a healthy status, with clinical effects that are not limited to
      the cardiovascular system but also include maternal and offspring health, growth
      and development, immune system disorders, cancer, cognitive function and
      psychological status. Multiple health organisations and scientific societies
      recommend increasing food-derived n-3 PUFA intake and also suggest that patients
      with documented coronary heart disease receive a minimum of 1000 mg/day of
      eicosapentaenoic acid and docosahexaenoic acid. The preventive and therapeutic
      effects of n-3 PUFAs appear to be largely dependent on the dosages employed and
      the characteristics of selected patients. So, in the era of personalised
      medicine, the time has come to move from generic advice to increase n-3 PUFA
      intake to a more evidence-based approach characterised by tailored indications to
      n-3 PUFA dietary or supplement consumption. This approach will require evaluation
      on a case-to-case basis the potential usefulness of n-3 PUFAs, taking into
      consideration their 'pleiotropic effects', the optimal dose for any given
      indication in relation to international guidelines, potential interactions with
      background therapy, possible side effects, differences in genetics and dietary
      response to supplementation, and the cost:benefit ratio, which is likely to vary
      as a function of differences in the range of fish intake in the diet.

PMID- 23871632
TI  - Preclinical evaluation of a new left atrial appendage occluder (Lifetech LAmbreTM
      device) in a canine model.
AB  - OBJECTIVES: The study evaluated the feasibility and safety of a novel left atrial
      appendage (LAA) occluder (LAmbreTM, Lifetech Scientific Corp., China) in canines.
      BACKGROUND: Transcatheter LAA occlusion is comparable to warfarin in preventing
      atrial fibrillation-related strokes. METHODS: Twenty-two healthy dogs (28 +/- 3
      kg) received LAmbre implants. The device is delivered by an 8-10 French sheath
      and has full recapture and repositioning capabilities. All dogs received 1-week
      antibiotics and 4-week aspirin (80 mg daily) after implants and they were
      sacrificed in groups at Days 1-3 (n = 5), 1- (n = 7), 3- (n = 4) and 6-months (n
      = 6) for pathological examinations. Transthoracic echocardiography (TTE) was
      performed immediately after implant, at Day 3 and before sacrifice. RESULTS: The
      LAmbre was successfully implanted, retrieved, repositioned and re-implanted in
      all dogs. The mean implant size was 24 +/- 3 mm and the device chosen was 36 +/-
      7% larger than the measured landing zone diameter. Improper device selection
      (only 21% oversizing) resulted in dislodgement and death of 1 dog on Day 3. Post
      implant angiography and TTE showed well-positioned device without pericardial
      effusion or impingement on surrounding structures. Late complications included
      device-related thrombus at 1 month (n = 1) and clinically insignificant
      pericardial effusion at Day 3 (n = 1). Complete healing on the atrial facing
      surface with optimal LAA obliteration was confirmed by gross and microscopic
      examinations in dogs that have been followed up >=3 months (n = 10). No infarct
      was detected in major organs. CONCLUSIONS: Our preliminary data suggested the
      LAmbreTM device is feasible with high success rate in canines. Further studies
      are needed to evaluate its safety and efficacy.

PMID- 23871633
TI  - Subcutaneous fat thickness, but not epicardial fat thickness, parallels weight
      reduction three months after bariatric surgery: a cardiac magnetic resonance
      study.

PMID- 23871634
TI  - Reduction of neurofilaments following renal denervation with radiofrequency
      current in a sheep model.

PMID- 23871635
TI  - Association between circulating microRNAs, cardiovascular risk factors and
      outcome in patients with acute myocardial infarction.

PMID- 23871636
TI  - The impact of electrocardiogram-guided, direct-targeting intervention of the
      infarct-related artery on the door-to-balloon time: a pilot study.

PMID- 23871637
TI  - A core human primary tumor angiogenesis signature identifies the endothelial
      orphan receptor ELTD1 as a key regulator of angiogenesis.
AB  - Limited clinical benefits derived from anti-VEGF therapy have driven the
      identification of new targets involved in tumor angiogenesis. Here, we report an
      integrative meta-analysis to define the transcriptional program underlying
      angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein
      coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4
      signaling. Extensive analysis of multiple cancer types demonstrates significant
      upregulation of ELTD1 in tumor-associated endothelial cells, with a higher
      expression correlating with favorable prognosis. Importantly, ELTD1 silencing
      impairs endothelial sprouting and vessel formation in vitro and in vivo,
      drastically reducing tumor growth and greatly improving survival. Collectively,
      these results provide insight into the regulation of tumor angiogenesis and
      highlight ELTD1 as key player in blood vessel formation.

PMID- 23871638
TI  - Promotion and prevention of autoimmune disease by CD8+ T cells.
AB  - Until recently, little was known about the importance of CD8+ T effectors in
      promoting and preventing autoimmune disease development. CD8+ T cells can oppose
      or promote autoimmune disease through activities as suppressor cells and as
      cytotoxic effectors. Studies in several distinct autoimmune models and data from
      patient samples are beginning to establish the importance of CD8+ T cells in
      these diseases and to define the mechanisms by which these cells influence
      autoimmunity. CD8+ effectors can promote disease via dysregulated secretion of
      inflammatory cytokines, skewed differentiation profiles and inappropriate
      apoptosis induction of target cells, and work to block disease by eliminating
      self-reactive cells and self-antigen sources, or as regulatory T cells. Defining
      the often major contribution of CD8+ T cells to autoimmune disease and
      identifying the mechanisms by which they alter the pathogenesis of disease is a
      rapidly expanding area of study and will add valuable information to our
      understanding of the kinetics, pathology and biology of autoimmune disease. 

PMID- 23871639
TI  - The interplay between regulatory and effector T cells in autoimmune hepatitis:
      Implications for innovative treatment strategies.
AB  - Autoimmune hepatitis is an immuno-mediated inflammatory liver disorder of unknown
      etiology and is characterized by hypergammaglobulinaemia, circulating
      autoantibodies and interface hepatitis. The disease may often present as an acute
      icteric hepatitis, or run an insidious and progressive course, and in most of the
      cases it is expected to evolve toward liver cirrhosis and end-stage liver
      failure, without prompt and appropriate treatment with steroids and other
      immunosuppressive drugs. Nonetheless, several patients are non-responsive or
      become non-tolerant to conventional therapy with prednisone/prednisolone with or
      without azathioprine. Recent findings highlight the role of the interplay between
      CD4+CD25+ regulatory T cells and Th17 cells in the pathogenesis of autoimmune
      hepatitis. A numerical and functional imbalance between regulatory and effector
      cells in favor of the latter appears to be pivotal in the progression of the
      disease. In addition, the intra-hepatic microenvironment of autoimmune hepatitis
      is particularly rich in pro-inflammatory cytokines such as IL-6, IL-17, IL-23, IL
      1beta which play a crucial role in perpetuating and expanding effector cells and
      subsequent liver damage, whereas regulatory T cells are greatly disadvantaged and
      inhibited in such polarized habitat. Novel therapeutic interventions should aim
      at modulating the intra-hepatic pro-inflammatory milieu while favoring the
      expansion of regulatory T cells. Liver autoantigen-specific regulatory T cells
      generated and expanded in vitro from patients' own cells might offer a
      potentially curative approach to autoimmune hepatitis by inhibiting effector
      cells of the same specificity without inducing pan-immunosuppression. 

PMID- 23871640
TI  - The limitations and hidden gems of the epidemiology of primary biliary cirrhosis.
AB  - Epidemiology is expected to provide important clues to our understanding of the
      enigmatic etiopathogenesis of primary biliary cirrhosis (PBC). First, a
      systematic review of population based studies indicated a wide range in the
      yearly incidence (0.33-5.8/100.000) and point prevalence (1.91-40.2/100.000)
      rates. Though different ethnic representations may also contribute it is likely
      that methodological issues, based on the retrospective survey of diagnosed cases,
      and time trend play a major role, also in view of the prolonged asymptomatic
      period of the disease. Of note, the highest prevalence rates (35-40/100.000) were
      found in areas characterized by high medical awareness and easier access to
      healthcare. Second, the search for serum AMA in unselected population sera may
      identify the largest possible number of patients who have or will develop the
      disease. Indeed, a surprisingly high AMA prevalence rate, ranging between 0.43
      and 1%, appears likely in the general population despite the lack of adequate
      work-up in most studies. Third, the median female to male ratio for PBC is
      classically accepted as 9-10:1 but is significantly lower for AMA prevalence
      (2.5:1), death certificates for PBC (4.3:1) and liver transplantation (6:1), thus
      suggesting that PBC in men may be underdiagnosed in early stages or manifest a
      more severe progression. Lastly, studies of both PBC and serum AMA prevalence
      among family members and monozygotic twins strongly support the role played by
      genetic factors in the etiopathogenesis of the disease. In conclusion, PBC
      epidemiology is far from being a closed case and the numerous open issues will be
      solved through a collaborative effort and powerful data mining tools. 

PMID- 23871641
TI  - The eye: A window to the soul of the immune system.
AB  - The eye is considered as an immune privileged site, and with good reason. It has
      evolved a variety of molecular and cellular mechanisms that limit immune
      responses to preserve vision. For example, the cornea is mainly protected from
      autoimmunity by the lack of blood and lymphatic vessels, whereas the retina-blood
      barrier is maintained in an immunosuppressive state by the retinal pigment
      epithelium. However, there are several scenarios in which immune privilege is
      altered and the eye becomes susceptible to immune attack. In this review, we
      highlight the role of the immune system in two clinical conditions that affect
      the anterior and posterior segments of the eye: corneal transplantation and age
      related macular degeneration. Interestingly, crosstalk between the innate and
      adaptive immune systems is critical in both acute and chronic inflammatory
      responses in the eye, with T cells playing a central role in combination with
      neutrophils and macrophages. In addition, we emphasize the advantage of using the
      eye as a model for in vivo longitudinal imaging of the immune system in action.
      Through this technique, it has been possible to identify functionally distinct
      intra-graft motility patterns of responding T cells, as well as the importance of
      chemokine signaling in situ for T cell activation. The detailed study of ocular
      autoimmunity could provide novel therapeutic strategies for blinding diseases
      while also providing more general information on acute versus chronic
      inflammation. 

PMID- 23871642
TI  - Hair and scalp evaluation: the trichogram.
AB  - Hair and scalp evaluation techniques can be classified into 3 categories:
      noninvasive methods (clinical history, general examination, inspection and
      palpation of the hair and scalp, photography, dermoscopy, etc.); semi-invasive
      methods (the trichogram); and invasive methods (biopsy). In this article, we
      provide a practical guide on how to evaluate hair and scalp conditions in the
      dermatology office. 

PMID- 23871643
TI  - Actas 2.0: Actas Dermosifiliograficas joins the world of social networking.

PMID- 23871644
TI  - Composition, diversity and distribution of microbenthos across the intertidal
      zones of Ryazhkov Island (the White Sea).
AB  - The composition and distribution of the main unicellular eukaryotic groups
      (diatom algae, ciliates, dinoflagellates (DF), other phototrophic (PF) and
      heterotrophic flagellates (HF)) were investigated in sandy sediments at five
      stations allocated across the tidal sheltered beach of the White Sea. Overall, 75
      diatoms, 98 ciliates, 16 DF, 3 PF and 34 HF species were identified; some are new
      records for the White Sea. Common species for each group are illustrated. Diatoms
      and ciliates showed high alpha-diversity (species richness per sample), whereas
      flagellates were characterized by high beta-diversity (species turnover across
      the intertidal flat). Each group demonstrated its own spatial pattern that was
      best matched with its own subset of abiotic variables, reflecting group-specific
      responses to environmental gradients. Species richness increased from the upper
      intertidal zone seaward for ciliates but decreased for HF, whereas autotrophs
      showed a relatively uniform pattern with a slight peak at the mid-intertidal
      zone. Across the littoral zone, all groups showed distinct compositional changes;
      however, the position of the boundary between "upper" and "lower" intertidal
      communities varied among groups. Most of the species found at Ryazhkov Island are
      known from many other regions worldwide, indicating a wide geographic
      distribution of microbial eukaryotic species. 

PMID- 23871645
TI  - Cell cycle-dependent modulations of fenestrin expression in Tetrahymena
      pyriformis.
AB  - In Tetrahymena, besides apparent cell polarity generated by specialized cortical
      structures, several proteins display a specific asymmetric distribution
      suggesting their involvement in the generation and the maintenance of cell
      polarization. One of these proteins, a membrane skeleton protein called
      fenestrin, forms an antero-posterior gradient, and is accepted as a marker of
      cell polarity during different cellular processes, such as cell division or oral
      replacement. In conjugating cells, fenestrin forms an intracytoplasmic net which
      participates in pronuclear exchange. The function of fenestrin is still unknown.
      To better understand the role of fenestrin we characterized this protein in an
      amicronuclear Tetrahymena pyriformis. We show that in this ciliate not only does
      fenestrin localization change in a cell division-dependent manner, but its mRNA
      and protein level is also cell cycle-regulated. We determine that the two
      available anti-fenestrin antibodies, 3A7 and 9A7, recognize different pools of
      fenestrin isoforms, and that 9A7 is the more general. In addition, our results
      indicate that fenestrin is a phosphoprotein. We also show that the level of
      fenestrin in the amicronuclear T. pyriformis and the amicronuclear BI3840 strain
      of T. thermophila is several times lower than in micronuclear T. thermophila. 

PMID- 23871646
TI  - Unbalanced 11;18 translocation in an acute erythroid leukemia after radioactive
      iodine therapy.
AB  - Therapy-related acute myeloid leukemia (t-AML) is well described after
      chemotherapy or radiotherapy for diverse malignancies. Radioisotope therapy is
      also recognized as a less-common cause of t-AML. We describe a patient with acute
      erythroid leukemia after radioactive iodine administration for papillary thyroid
      cancer, with an unbalanced 11;18 translocation resulting in three copies of 11q,
      including the MLL gene. Although an increased incidence of chronic myeloid
      leukemia has been documented after radioactive iodine exposure, acute leukemia in
      this setting has been less frequently seen. Moreover, to our knowledge, the
      chromosome abnormality present in our patient has not been previously reported.
      The literature on cytogenetic abnormalities in t-AML after radioactive iodine
      administration is reviewed. 

PMID- 23871647
TI  - Malposition of the pacemaker lead in the left ventricle.

PMID- 23871648
TI  - The impact of cervical surgery on intervention and preterm birth in high-risk
      pregnant women.

PMID- 23871649
TI  - Expression profile of cytokine genes in Fugu monocytes stimulated with TLR
      agonists.
AB  - Monocytes are antigen-presenting cells (APCs) in mammals. Antigen presentation by
      monocytes via costimulatory molecules was recently confirmed in the Japanese
      pufferfish Fugu rubripes (also known as Takifugu rubripes) (Sugamata et al.,
      2009[1]). However, no detailed investigations examining how cytokine gene
      expression regulates the activation/differentiation of these cells have been
      conducted to date. Therefore, in this study, the expression of cytokine genes in
      Fugu monocytes stimulated with TLR agonists (LPS, polyI:C, and IMQ) was profiled.
      First, the morphological changes and phagocytic activity of stimulated monocytes
      were examined. At 5 days post-stimulation, the ratio of activated to inactivated
      monocytes increased (as determined by FCM analysis), and the phagocytic activity
      of the cells was higher (5-15%) than that of nonactivated cells. Analysis of
      cytokine gene expression in stimulated monocytes revealed that the genes encoding
      CSF-1b and IFN-gamma are important cytokines in activation/differentiation of
      monocytes/macrophages, and that genes encoding inflammatory cytokines such as IL
      1beta, IL-6, IL-18, and TNF-alpha are upregulated by stimulation. The present
      study revealed the types of cytokines expressed in Fugu monocytes stimulated with
      TLR agonists.

PMID- 23871650
TI  - Expression of Wnt signaling skeletal development genes in the cartilaginous fish,
      elephant shark (Callorhinchus milii).
AB  - Jawed vertebrates (Gnasthostomes) are broadly separated into cartilaginous fishes
      (Chondricthyes) and bony vertebrates (Osteichthyes). Cartilaginous fishes are
      divided into chimaeras (e.g. ratfish, rabbit fish and elephant shark) and
      elasmobranchs (e.g. sharks, rays and skates). Both cartilaginous fish and bony
      vertebrates are believed to have a common armoured bony ancestor (Class
      Placodermi), however cartilaginous fish are believed to have lost bone. This
      study has identified and investigated genes involved in skeletal development in
      vertebrates, in the cartilaginous fish, elephant shark (Callorhinchus milii).
      Ctnnb1 (beta-catenin), Sfrp (secreted frizzled protein) and a single Sost or
      Sostdc1 gene (sclerostin or sclerostin domain-containing protein 1) were
      identified in the elephant shark genome and found to be expressed in a number of
      tissues, including cartilage. beta-catenin was also localized in several elephant
      shark tissues. The expression of these genes, which belong to the Wnt/beta
      catenin pathway, is required for normal bone formation in mammals. These findings
      in the cartilaginous skeleton of elephant shark support the hypothesis that the
      common ancestor of cartilaginous fishes and bony vertebrates had the potential
      for making bone. 

PMID- 23871651
TI  - Obtaining maximum muscle excitation for normalizing shoulder electromyography in
      dynamic contractions.
AB  - Muscle specific maximal voluntary isometric contractions (MVIC) are commonly used
      to elicit reference amplitudes to normalize electromyographic signals (EMG). It
      has been questioned whether this is appropriate for normalizing EMG from dynamic
      contractions. This study compares EMG amplitude when shoulder muscle activity
      from dynamic contractions is normalized to isometric and isokinetic maximal
      excitation as well as a hybrid approach currently used in our laboratory.
      Anterior, middle and posterior deltoid, upper and lower trapezius, pectoralis
      major, latissimus dorsi and infraspinatus were monitored during (1) manually
      resisted MVICs, and (2) maximum voluntary dynamic concentric contractions (MVDC)
      on an isokinetic dynamometer. Dynamic contractions were performed (a) at 30
      degrees /s about the longitudinal, frontal and sagittal axes of the shoulder, and
      (b) during manual bi-rotation of a tilted wheel at 120 degrees /s. EMG from the
      wheel task was normalized to the maximum excitation from (i) the muscle specific
      MVIC, (ii) from any MVIC (MVICALL), (iii) for any MVDC, (iv) from any exertion
      (maximum experimental excitation, MEE). Mean EMG from the wheel task was up to
      45% greater when normalized to muscle specific isometric contractions (method i)
      than when normalized to MEE (method iv). Seventy-five percent of MEE's occurred
      during MVDCs. This study presents an 20 useful and effective process for
      obtaining the greatest excitation from the shoulder muscles when normalizing
      dynamic efforts. 

PMID- 23871652
TI  - Electromyography responses of pediatric and young adult volunteers in low-speed
      frontal impacts.
AB  - No electromyography (EMG) responses data exist of children exposed to dynamic
      impacts similar to automotive crashes, thereby, limiting active musculature
      representation in computational occupant biomechanics models. This study measured
      the surface EMG responses of three neck, one torso and one lower extremity
      muscles during low-speed frontal impact sled tests (average maximum acceleration:
      3.8g; rise time: 58.2ms) performed on seated, restrained pediatric (n=11, 8
      14years) and young adult (n=9, 18-30years) male subjects. The timing and
      magnitude of the EMG responses were compared between the two age groups. Two
      normalization techniques were separately implemented and evaluated: maximum
      voluntary EMG (MVE) and neck cross-sectional area (CSA). The MVE-normalized EMG
      data indicated a positive correlation with age in the rectus femoris for EMG
      latency; there was no correlation with age for peak EMG amplitudes for the
      evaluated muscles. The cervical paraspinous exhibited shorter latencies compared
      with the other muscles (2-143ms). Overall, the erector spinae and rectus femoris
      peak amplitudes were relatively small. Neck CSA-normalized peak EMG amplitudes
      negatively correlated with age for the cervical paraspinous and
      sternocleidomastoid. These data can be useful to incorporate active musculature
      in computational models, though it may not need to be age-specific in low-speed
      loading environments. 

PMID- 23871653
TI  - Increased hip internal abduction moment and reduced speed are the gait strategies
      used by women with knee osteoarthritis.
AB  - The purpose of this study was to identify the gait strategies in women with mild
      and moderate knee osteoarthritis (OA). Forty women diagnosed with OA of the knee
      and 40 healthy women participated in the study. Toe-out progression angle, trunk
      lateral lean, hip internal abduction moment and gait speed were measured using
      Qualisys ProReflex System and two force plates. Principal component analysis was
      applied to extract features from the gait waveforms data that characterized the
      waveforms main modes of temporal variation. Discriminant analysis with a stepwise
      model was conducted to determine which strategies could best discriminate groups.
      According to the discriminant model, the PC2 of the internal abduction moment of
      the hip and the gait speed were the most discriminatory variables between the
      groups. The OA group showed decreased gait speed, decreased hip internal
      abduction moment during the loading response phase, and increased hip internal
      abduction moment during the mid and terminal stance phases. Interventions that
      may increase hip internal abduction moment, such as the strengthening of the hip
      abductors muscles, may benefit women with knee OA. Training slower than normal
      gait speeds must be considered in light of potential adverse implications on
      overall physical function, daily tasks, and safety. 

PMID- 23871654
TI  - Hydrogen peroxide stress provokes a metabolic reprogramming in Pseudomonas
      fluorescens: enhanced production of pyruvate.
AB  - Pseudomonas fluorescens invoked a metabolic reconfiguration that resulted in
      enhanced production of pyruvate under the challenge of hydrogen peroxide (H2O2).
      Although this stress led to a sharp reduction in the activities of numerous
      tricarboxylic acid (TCA) cycle enzymes, there was a marked increase in the
      activities of catalase and various NADPH-generating enzymes to counter the
      oxidative burden. The upregulation of phosphoenolpyruvate synthase (PEPS) and
      pyruvate kinase (PK) coupled with the reduction of pyruvate dehydrogenase (PDH)
      in the H2O2-challenged cells appear to be important contributors to the elevated
      levels of pyruvate found in these bacteria. Increased pyruvate synthesis was
      evident in the presence of a variety of carbon sources including d-glucose.
      Intact cells rapidly consumed d-glucose with the concomitant formation of this
      monocarboxylic acid. At least a 12-fold increase in pyruvate production within 1h
      was observed in the stressed cells. These findings may be exploited in the
      development of technologies aimed at the conversion of carbohydrates into
      pyruvate.

PMID- 23871655
TI  - Identification of a T7 RNA polymerase variant that permits the enzymatic
      synthesis of fully 2'-O-methyl-modified RNA.
AB  - T7 RNA polymerase is an important biocatalyst that is used in diverse
      biotechnological applications such as in vitro transcription or protein
      expression. The enzyme displays high substrate specificity which is payed by
      significant limitations regarding incorporation of synthetic nucleotide analogs.
      Of specific interest is enzymatic synthesis of 2'-O-methyl-modified RNA as these
      nucleic acids exhibit improved biochemical and pharmacokinetic properties that
      make them attractive for diagnostic and therapeutic purposes. We report here on
      the development of an activity-based selection/screening approach for assessing
      polymerase activities in the presence of 2'-O-methyl-modified nucleotides, and on
      the identification of one variant T7 RNA polymerase which is capable of
      synthesizing all-2'-O-methyl RNA. 

PMID- 23871656
TI  - Phoenix 2: a locally installable large-scale 16S rRNA gene sequence analysis
      pipeline with Web interface.
AB  - We have developed Phoenix 2, a ribosomal RNA gene sequence analysis pipeline,
      which can be used to process large-scale datasets consisting of more than one
      hundred environmental samples and containing more than one million reads
      collectively. Rapid handling of large datasets is made possible by the removal of
      redundant sequences, pre-partitioning of sequences, parallelized clustering per
      partition, and subsequent merging of clusters. To build the pipeline, we have
      used a combination of open-source software tools and custom-developed Perl
      scripts. For our project we utilize hardware-accelerated searches, but it is
      possible to reconfigure the analysis pipeline for use with generic computing
      infrastructure only, with a considerable reduction in speed. The set of analysis
      results produced by Phoenix 2 is comprehensive, including taxonomic annotations
      using multiple methods, alpha diversity indices, beta diversity measurements, and
      a number of visualizations. To date, the pipeline has been used to analyze more
      than 1500 environmental samples from a wide variety of microbial communities,
      which are part of our Hydrocarbon Metagenomics Project
      (http://www.hydrocarbonmetagenomics.com). The software package can be installed
      as a local software suite with a Web interface. Phoenix 2 is freely available
      from http://sourceforge.net/projects/phoenix2. 

PMID- 23871657
TI  - Predicting defibrillation success in sudden cardiac arrest patients.
AB  - Although the importance of quality cardiopulmonary resuscitation (CPR) and its
      link to survival is still emphasized, there has been recent debate about the
      balance between CPR and defibrillation, particularly for long response times.
      Defibrillation shocks for ventricular fibrillation (VF) of recently perfused
      hearts have high success for the return of spontaneous circulation (ROSC), but
      hearts with depleted adenosine triphosphate (ATP) stores have low recovery rates.
      Since quality CPR has been shown to both slow the degradation process and restore
      cardiac viability, a measurement of patient condition to optimize the timing of
      defibrillation shocks may improve outcomes compared to time-based protocols.
      Researchers have proposed numerous predictive features of VF and shockable
      ventricular tachycardia (VT) which can be computed from the electrocardiogram
      (ECG) signal to distinguish between the rhythms which convert to spontaneous
      circulation and those which do not. We looked at the shock-success prediction
      performance of thirteen of these features on a single evaluation database
      including the recordings from 116 out-of-hospital cardiac arrest patients which
      were collected for a separate study using defibrillators in ambulances and
      medical centers in 4 European regions and the US between March 2002 and September
      2004. A total of 469 shocks preceded by VF or shockable VT rhythm episodes were
      identified in the recordings. Based on the experts' annotation for the post-shock
      rhythm, the shocks were categorized to result in either pulsatile (ROSC) or non
      pulsatile (no-ROSC) rhythm. The features were calculated on a 4-second ECG
      segment prior to the shock delivery. These features examined were: Mean
      Amplitude, Average Peak-Peak Amplitude, Amplitude Range, Amplitude Spectrum
      Analysis (AMSA), Peak Frequency, Centroid Frequency, Spectral Flatness Measure
      (SFM), Energy, Max Power, Centroid Power, Power Spectrum Analysis (PSA), Mean
      Slope, and Median Slope. Statistical hypothesis tests (two-tailed t-test and
      Wilcoxon with 5% significance level) were applied to determine if the means and
      medians of these features were significantly different between the ROSC and no
      ROSC groups. The ROC curve was computed for each feature, and Area Under the
      Curve (AUC) was calculated. Specificity (Sp) with Sensitivity (Se) held at 90% as
      well as Se with Sp held at 90% was also computed. All features showed
      statistically different mean and median values between the ROSC and no-ROSC
      groups with all p-values less than 0.0001. The AUC was >76% for all features. For
      Sp = 90%, the Se range was 33-45%; for Se = 90%, the Sp range was 49-63%. The
      features showed good shock-success prediction performance. We believe that a
      defibrillator employing a clinical decision tool based on these features has the
      potential to improve overall survival from cardiac arrest. 

PMID- 23871658
TI  - Early repolarization ECG pattern in the Finnish general population.

PMID- 23871659
TI  - Mycorrhiza-induced resistance: more than the sum of its parts?
AB  - Plants can develop an enhanced defensive capacity in response to infection by
      arbuscular mycorrhizal fungi (AMF). This 'mycorrhiza-induced resistance' (MIR)
      provides systemic protection against a wide range of attackers and shares
      characteristics with systemic acquired resistance (SAR) after pathogen infection
      and induced systemic resistance (ISR) following root colonisation by non
      pathogenic rhizobacteria. It is commonly assumed that fungal stimulation of the
      plant immune system is solely responsible for MIR. In this opinion article, we
      present a novel model of MIR that integrates different aspects of the induced
      resistance phenomenon. We propose that MIR is a cumulative effect of direct plant
      responses to mycorrhizal infection and indirect immune responses to ISR-eliciting
      rhizobacteria in the mycorrhizosphere. 

PMID- 23871660
TI  - Validation of a radiobiological model for low-dose-rate prostate boost focal
      therapy treatment planning.
AB  - PURPOSE: Low-dose-rate brachytherapy using iodine-125 seeds is a highly
      efficacious treatment for low-risk prostate cancer. We propose a bioeffect model
      may be used to target an ablative dose to the tumor with a lower, therapeutic
      dose to low-risk regions to maintain high rates of tumor control with reduced
      toxicity. We report on the validation of the model and derivation of the optimal
      cutpoint value of tumor control probability (TCP) that predicts for freedom from
      biochemical failure. METHODS AND MATERIALS: The TCP was calculated from
      postimplant dosimetry data for 423 prostate cancer patients from three Australian
      institutions. To apply the model, the prostate was mathematically divided into 12
      subsections with tumor characteristics, including a nonuniform distribution of
      tumor cell density, derived from the literature. RESULTS: When TCP values were
      above and below 0.62, the 5-year freedom from biochemical failure were 93.7% (95%
      confidence interval [CI], 90.4, 96.4%) and 88.8% (95% confidence interval, 81.3,
      94.5%), respectively (p = 0.004). CONCLUSIONS: Using postimplant dosimetry data,
      the TCP model was able to predict for freedom from biochemical failure. The
      cutpoint value that would be used clinically depends on the selection of the
      model parameters, but the potential for the model to be used in the optimization
      of treatment planning is demonstrated.

PMID- 23871661
TI  - Comparison of dose-escalated, image-guided radiotherapy vs. dose-escalated, high
      dose-rate brachytherapy boost in a modern cohort of intermediate-risk prostate
      cancer patients.
AB  - PURPOSE: We compared outcomes in intermediate-risk prostate cancer patients
      treated with dose-escalated adaptive image-guided radiation therapy (IGRT) or
      dose-escalated high-dose-rate brachytherapy boost (HDR-B). METHODS AND MATERIALS:
      Patients with intermediate-risk prostate cancer by National Comprehensive Cancer
      Network criteria were treated with either CT-based off-line adaptive IGRT (n =
      734) or HDR-B (n = 282). IGRT was delivered with 3D-conformal or intensity
      modulated radiation therapy with a median dose of 77.4 Gy. For HDR-B, the whole
      pelvis received a median 46 Gy, and the prostate 2 implants of 9.5 Gy (n = 71),
      10.5 Gy (n = 155), or 11.5 Gy (n = 56). RESULTS: Median followup was 3.7 years
      for IGRT and 8.0 years for HDR-B (p < 0.001). Eight-year biochemical control was
      86% for IGRT and 91% for HDR-B (p = 0.22), disease-free survival 67% for IGRT and
      79% for HDR-B (p = 0.006), and overall survival 75% for IGRT and 86% for HDR-B (p
      = 0.009). Cause-specific survival (8-year, 100% vs. 99%), freedom from distant
      metastases (98% vs. 97%), and freedom from local recurrence (98% vs. 98%) did not
      differ (p > 0.50 each). A worse prognosis group was defined by percent positive
      prostate biopsy cores >50%, perineural invasion, or stage T2b-c, encompassing 260
      (35%) IGRT and 171 (61%) HDR-B patients. These patients evidenced a 5-year
      biochemical control of 96% for HDR-B and 87% for IGRT (p = 0.002). CONCLUSIONS:
      Dose-escalated IGRT and HDR-B both yield excellent clinical outcomes for patients
      with intermediate-risk prostate cancer. Improved biochemical control with HDR-B
      for patients with worse pretreatment characteristics suggests that a subgroup of
      intermediate-risk prostate cancer patients may benefit from dual-modality
      treatment.

PMID- 23871662
TI  - No stone left unturned: challenges encountered during recruitment of women with
      advanced ovarian cancer for a phase I study.
AB  - The recruitment and accrual of participants for cancer clinical trial research is
      often challenging. Chronic low accrual rates negatively influence the findings
      and generalizability that can be drawn from the available pool of research. There
      is a need for further evidence regarding both unsuccessful and successful
      approaches and useful strategies that investigators have used to counter common
      recruitment challenges. During recruitment for an intervention study examining
      the safety, efficacy, and feasibility of a potentially novel supportive therapy,
      a variety of steps were taken to avoid and subsequently overcome potential and
      real recruitment challenges the investigators faced. In this article the authors
      provide an overview of common recruitment challenges as well as the actual
      challenges encountered, procedures and strategies implemented to counter these
      challenges, while investigating the combined intervention of flaxseed oil,
      fasting, caffeine, and exercise in women with recurrent or multi-drug resistant
      stage III or IV ovarian cancer. 

PMID- 23871664
TI  - Effects of genetic variation on the E. coli host-circuit interface.
AB  - Predictable operation of engineered biological circuitry requires the knowledge
      of host factors that compete or interfere with designed function. Here, we
      perform a detailed analysis of the interaction between constitutive expression
      from a test circuit and cell-growth properties in a subset of genetic variants of
      the bacterium Escherichia coli. Differences in generic cellular parameters such
      as ribosome availability and growth rate are the main determinants (89%) of
      strain-specific differences of circuit performance in laboratory-adapted strains
      but are responsible for only 35% of expression variation across 88 mutants of E.
      coli BW25113. In the latter strains, we identify specific cell functions, such as
      nitrogen metabolism, that directly modulate circuit behavior. Finally, we expose
      aspects of carbon metabolism that act in a strain- and sequence-specific manner.
      This method of dissecting interactions between host factors and heterologous
      circuits enables the discovery of mechanisms of interference necessary for the
      development of design principles for predictable cellular engineering. 

PMID- 23871663
TI  - Rhinovirus infection causes steroid resistance in airway epithelium through
      nuclear factor kappaB and c-Jun N-terminal kinase activation.
AB  - BACKGROUND: Although inhaled glucocorticoids are the mainstays of asthma
      treatment, they are poorly effective at treating and preventing virus-induced
      asthma exacerbations. The major viruses precipitating asthma exacerbations are
      rhinoviruses. OBJECTIVE: We sought to evaluate whether rhinovirus infection
      interferes with the mechanisms of action of glucocorticoids. METHODS: Cultured
      primary human bronchial or transformed (A549) respiratory epithelial cells were
      infected with rhinovirus 16 (RV-16) before dexamethasone exposure. Glucocorticoid
      receptor (GR) alpha nuclear translocation, glucocorticoid response element (GRE)
      binding, and transactivation/transrepression functional readouts were evaluated
      by using immunocytochemistry, Western blotting, DNA binding assays, real-time
      quantitative PCR, coimmunoprecipitation, and ELISA techniques. Specific
      inhibitors of c-Jun N-terminal kinase (JNK) and of IkappaB kinase (IKK) were used
      to investigate the involvement of intracellular signaling pathways. RESULTS: RV
      16 infection impaired dexamethasone-dependent (1) inhibition of IL-1beta-induced
      CXCL8 release, (2) induction of mitogen-activated protein kinase phosphatase 1
      gene expression, and (3) binding of GR to GREs in airway epithelial cells. This
      was associated with impaired GRalpha nuclear translocation, as assessed by means
      of both immunochemistry (54.0% +/- 6.8% vs 24.7% +/- 3.8% GR-positive nuclei
      after 10 nmol/L dexamethasone treatment in sham- or RV-16-infected cells,
      respectively; P < .01) and Western blotting. RV-16 infection induced nuclear
      factor kappaB activation and GRalpha phosphorylation, which were prevented by
      inhibitors of IKK2 and JNK, respectively. In rhinovirus-infected cells the
      combination of JNK and IKK2 inhibitors totally restored dexamethasone suppression
      of CXCL8 release, induction of mitogen-activated protein kinase phosphatase 1
      gene expression, and GRalpha nuclear translocation. CONCLUSION: RV-16 infection
      of human airway epithelium induces glucocorticoid resistance. Inhibition of RV-16
      induced JNK and nuclear factor kappaB activation fully reversed rhinovirus
      impairment of both GRalpha nuclear translocation and the
      transactivation/transrepression activities of glucocorticoids.

PMID- 23871665
TI  - Thermodynamic stabilization of the folded domain of prion protein inhibits prion
      infection in vivo.
AB  - Prion diseases, or transmissible spongiform encephalopathies (TSEs), are
      associated with the conformational conversion of the cellular prion protein,
      PrP(C), into a protease-resistant form, PrP(Sc). Here, we show that mutation
      induced thermodynamic stabilization of the folded, alpha-helical domain of PrP(C)
      has a dramatic inhibitory effect on the conformational conversion of prion
      protein in vitro, as well as on the propagation of TSE disease in vivo.
      Transgenic mice expressing a human prion protein variant with increased
      thermodynamic stability were found to be much more resistant to infection with
      the TSE agent than those expressing wild-type human prion protein, in both the
      primary passage and three subsequent subpassages. These findings not only provide
      a line of evidence in support of the protein-only model of TSEs but also yield
      insight into the molecular nature of the PrP(C)->PrP(Sc) conformational
      transition, and they suggest an approach to the treatment of prion diseases. 

PMID- 23871667
TI  - Human pluripotent stem cells with distinct X inactivation status show molecular
      and cellular differences controlled by the X-Linked ELK-1 gene.
AB  - Female human pluripotent stem cells show vast heterogeneity regarding the status
      of X chromosome inactivation. By comparing the gene expression profile of cells
      with two active X chromosomes (XaXa cells) to that of cells with only one active
      X chromosome (XaXi cells), a set of autosomal genes was shown to be overexpressed
      in the XaXa cells. Among these genes, we found significant enrichment for genes
      regulated by the X-linked transcription factor ELK-1. Comparison of the phenotype
      of XaXa and XaXi cells demonstrated differences in programmed cell death and
      differentiation, implying some growth disadvantage of the XaXa cells.
      Interestingly, ELK-1-overexpressing cells mimicked the phenotype of XaXa cells,
      whereas knockdown of ELK-1 with small hairpin RNA mimicked the phenotype of XaXi
      cells. When cultured at low oxygen levels, these cellular differences were
      considerably weakened. Our analysis implies a role of ELK-1 in the differences
      between pluripotent stem cells with distinct X chromosome inactivation statuses. 

PMID- 23871666
TI  - NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its
      processing into regulatory small RNAs.
AB  - Autosomal-recessive loss of the NSUN2 gene has been identified as a causative
      link to intellectual disability disorders in humans. NSun2 is an RNA
      methyltransferase modifying cytosine-5 in transfer RNAs (tRNAs), yet the
      identification of cytosine methylation in other RNA species has been hampered by
      the lack of sensitive and reliable molecular techniques. Here, we describe miCLIP
      as an additional approach for identifying RNA methylation sites in
      transcriptomes. miCLIP is a customized version of the individual-nucleotide
      resolution crosslinking and immunoprecipitation (iCLIP) method. We confirm site
      specific methylation in tRNAs and additional messenger and noncoding RNAs
      (ncRNAs). Among these, vault ncRNAs contained six NSun2-methylated cytosines,
      three of which were confirmed by RNA bisulfite sequencing. Using patient cells
      lacking the NSun2 protein, we further show that loss of cytosine-5 methylation in
      vault RNAs causes aberrant processing into Argonaute-associated small RNA
      fragments that can function as microRNAs. Thus, impaired processing of vault
      ncRNA may contribute to the etiology of NSun2-deficiency human disorders. 

PMID- 23871669
TI  - Indian hedgehog controls proliferation and differentiation in skin tumorigenesis
      and protects against malignant progression.
AB  - Mutations in the hedgehog pathway drive the formation of tumors in many different
      organs, including the development of basal cell carcinoma in the skin. However,
      little is known about the role of epidermal Indian hedgehog (Ihh) in skin
      physiology. Using mouse genetics, we identified overlapping and distinct
      functions of Ihh in different models of epidermal tumorigenesis. Epidermal
      deletion of Ihh resulted in increased formation of benign squamous papilloma.
      Strikingly, Ihh-deficient mice showed an increase in malignant squamous cell
      carcinoma and developed lung and lymph node metastases. In a sebaceous gland
      tumor model, Ihh deficiency inhibited tumor cell differentiation. More
      mechanistically, IHH stimulated cell proliferation by activating the
      transcription factor GLI2 in human keratinocytes and human tumors. Thus, our
      results uncover important functions for Ihh signaling in controlling
      proliferation, differentiation, malignant progression, and metastasis of
      epithelial cancer, establishing Ihh as a gatekeeper for controlling the grade of
      tumor malignancy.

PMID- 23871668
TI  - Femtosecond laser ablation reveals antagonistic sensory and neuroendocrine
      signaling that underlie C. elegans behavior and development.
AB  - The specific roles of neuronal subcellular components in behavior and development
      remain largely unknown, even though advances in molecular biology and
      conventional whole-cell laser ablation have greatly accelerated the
      identification of contributors at the molecular and cellular levels. We
      systematically applied femtosecond laser ablation, which has submicrometer
      resolution in vivo, to dissect the cell bodies, dendrites, or axons of a sensory
      neuron (ASJ) in Caenorhabditis elegans to determine their roles in modulating
      locomotion and the developmental decisions for dauer, a facultative, stress
      resistant life stage. Our results indicate that the cell body sends out axonally
      mediated and hormonal signals in order to mediate these functions. Furthermore,
      our results suggest that antagonistic sensory dendritic signals primarily drive
      and switch polarity between the decisions to enter and exit dauer. Thus, the
      improved resolution of femtosecond laser ablation reveals a rich complexity of
      neuronal signaling at the subcellular level, including multiple neurite and
      hormonally mediated pathways dependent on life stage. 

PMID- 23871670
TI  - Innate immune-directed NF-kappaB signaling requires site-specific NEMO
      ubiquitination.
AB  - While the I kappa kinase (IKK) scaffolding protein NF-kappaB essential modulator
      (NEMO) binds to polyubiquitin chains to transmit inflammatory signals, NEMO
      itself is also ubiquitinated in response to a variety of inflammatory agonists.
      Although there have been hints that polyubiquitination of NEMO is essential for
      avoiding inflammatory disorders, the in vivo physiologic role of NEMO
      ubiquitination is unknown. In this work, we knock in a NEMO allele in which two
      major inflammatory agonist-induced ubiquitination sites cannot be ubiquitinated.
      We show that mice with a nonubiquitinatable NEMO allele display embryonic
      lethality. Heterozygous females develop inflammatory skin lesions, decreased B
      cell numbers, and hypercellular spleens. Embryonic lethality can be complemented
      by mating onto a TNFR1(-/-) background, at the cost of severe steatohepatitis and
      early mortality, and we also show that NEMO ubiquitination is required for
      optimal innate immune signaling responses. These findings suggest that NEMO
      ubiquitination is crucial for NF-kappaB activity in response to innate immune
      agonists. 

PMID- 23871672
TI  - Cracking the molecular origin of intrinsic tyrosine kinase activity through
      analysis of pathogenic gain-of-function mutations.
AB  - The basal (ligand-independent) kinase activity of receptor tyrosine kinases
      (RTKs) promotes trans-phosphorylation on activation loop tyrosines upon ligand
      induced receptor dimerization, thus upregulating intrinsic kinase activity and
      triggering intracellular signaling. To understand the molecular determinants of
      intrinsic kinase activity, we used X-ray crystallography and NMR spectroscopy to
      analyze pathogenic FGF receptor mutants with gradations in gain-of-function
      activity. These structural analyses revealed a "two-state" dynamic equilibrium
      model whereby the kinase toggles between an "inhibited," structurally rigid
      ground state and a more dynamic and heterogeneous active state. The pathogenic
      mutations have different abilities to shift this equilibrium toward the active
      state. The increase in the fractional population of FGF receptors in the active
      state correlates with the degree of gain-of-function activity and clinical
      severity. Our data demonstrate that the fractional population of RTKs in the
      active state determines intrinsic kinase activity and underscore how a slight
      increase in the active population of kinases can have grave consequences for
      human health. 

PMID- 23871673
TI  - Prognostic value of N-terminal pro-brain natriuretic Peptide in outpatients with
      hypertrophic cardiomyopathy.
AB  - In hypertrophic cardiomyopathy, the plasma levels of N-terminal pro-brain
      natriuretic peptide (NT-proBNP) correlate with functional capacity. However,
      their prognostic relevance remains unresolved. We followed up 183 stable
      outpatients with hypertrophic cardiomyopathy (age 50 +/- 17 years, 64% men) for
      3.9 +/- 2.8 years after NT-proBNP measurement. The primary end point included
      cardiovascular death, heart transplantation, resuscitated cardiac arrest, and
      appropriate implantable cardioverter-defibrillator intervention. The secondary
      end point (SE) included heart failure-related death or hospitalization,
      progression to end-stage disease, and stroke. The median NT-proBNP level was 615
      pg/ml (intertertile range 310 to 1,025). The incidence of the primary end point
      in the lower, middle, and upper tertiles was 0%, 1.3%, and 2.1% annually,
      respectively (overall p = 0.01). On multivariate analysis, the only independent
      predictors of the primary end point were NT-proBNP (hazard ratio for log
      transformed values 5.8, 95% confidence interval 1.07 to 31.6; p = 0.04) and a
      restrictive left ventricular filling pattern (hazard ratio 5.19, 95% confidence
      interval 1.3 to 21.9; p = 0.02). The NT-proBNP cutoff value of 810 pg/ml had the
      best sensitivity for the primary end point (88%), but the specificity was low
      (61%). The incidence of the SE in the lower, middle, and upper NT-proBNP tertiles
      was 4.6%, 12.0%, and 11.2% annually, respectively (overall p = 0.001). An NT
      proBNP level of <310 pg/ml was associated with a 75% reduction in the rate of SE
      compared with a level of >=310 pg/ml (hazard ratio 0.25, 95% confidence interval
      0.11 to 0.57; p = 0.001), independent of age, left ventricular outflow tract
      obstruction, or atrial fibrillation. In conclusion, in stable outpatients with
      hypertrophic cardiomyopathy, plasma NT-proBNP proved a powerful independent
      predictor of death and heart failure-related events. Although the positive
      predictive accuracy of an elevated NT-proBNP level was modest, low values
      reflected true clinical stability, suggesting the possibility of avoiding or
      postponing aggressive treatment options. 

PMID- 23871674
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy according to revised
      2010 task force criteria with inclusion of non-desmosomal phospholamban mutation
      carriers.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is frequently
      associated with desmosomal mutations. However, nondesmosomal mutations may be
      involved. The aim of this study was to assess the contribution of a phospholamban
      (PLN) gene mutation to ARVD/C diagnosis according to the revised 2010 task force
      criteria (TFC). In 142 Dutch patients (106 men, mean age 51 +/- 13 years) with
      proven ARVD/C (fulfillment of 2010 TFC for diagnosis), 5 known desmosomal genes
      (PKP2, DSP, DSC2, DSG2, and JUP) and the nondesmosomal PLN gene were screened.
      After genetic analysis, phenotypic characteristics of desmosomal versus PLN
      mutation carriers were compared. In 59 of 142 patients with ARVD/C (42%), no
      desmosomal mutation was found. In 19 of 142 patients (13%), the PLN founder
      mutation c.40_42delAGA (p.Arg14del) was identified. PLN mutation carriers more
      often had low-voltage electrocardiograms (p = 0.004), inverted T waves in leads
      V4 to V6 (p <0.001), and additional structural (p = 0.007) or functional (p =
      0.017) left ventricular impairment, whereas desmosomal mutation carriers had more
      solitary right ventricular abnormalities. The revised TFC included 21 of 142
      patients with proven ARVD/C who did not meet the 1994 TFC, including 7 PLN
      mutation carriers. In conclusion, there is a substantial contribution of PLN
      mutation to ARVD/C diagnosis by the 2010 TFC. In 32% of patients (19 of 59) with
      genetically unexplained proven ARVD/C, this nondesmosomal mutation was found. PLN
      mutation carriers have ARVD/C characteristics, including important right
      ventricular involvement, and additionally more often low-voltage
      electrocardiograms, inverted T waves in the left precordial leads, and left
      ventricular involvement. 

PMID- 23871675
TI  - Effectiveness of percutaneous closure of patent foramen ovale for hypoxemia.
AB  - The aim of this study was to evaluate the ability of percutaneous patent foramen
      ovale (PFO) closure to improve systemic hypoxemia. Although PFO-mediated right-to
      left shunt (RTLS) is associated with hypoxemia, the ability of percutaneous
      closure to ameliorate hypoxemia is unknown. Between 2004 and 2009, 97 patients
      who underwent PFO closure for systemic hypoxemia and dyspnea that was
      disproportionate to underlying lung disease were included for evaluation. All
      patients exhibited PFO-mediated RTLS as determined by agitated saline
      echocardiography. Procedural success was defined as implantation of a device
      without major complications and mild or no residual shunt at 6 months. Clinical
      success was defined as a composite of an improvement in New York Heart
      Association (NYHA) functional class, reduction of dyspnea symptoms, or decreased
      oxygen requirement. Procedural success was achieved in 96 of 97 (99%), and
      clinical success was achieved in 68 of 97 (70%). The presence of any moderate or
      severe interatrial shunt by agitated saline study (odds ratio [OR] = 4.7; p
      <0.024), NYHA class at referral (OR = 2.9; p <0.0087), and 10-year increase in
      age (OR = 1.8; p <0.0017) increased likelihood of clinical success. In contrast,
      a pulmonary comorbidity (OR = 0.18; p <0.005) and male gender (OR = 0.30; p
      <0.017) decreased the likelihood of success. In conclusion, based on the largest
      single-center experience of patients referred for PFO closure for systemic
      hypoxemia, PFO closure was a mechanically effective procedure with an associated
      improvement in echocardiographic evidence of RTLS, NYHA functional class, and
      oxygen requirement. 

PMID- 23871671
TI  - SUMO-2 and PIAS1 modulate insoluble mutant huntingtin protein accumulation.
AB  - A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin
      (HTT) protein, which may be regulated by posttranslational modifications. Here,
      we define the primary sites of SUMO modification in the amino-terminal domain of
      HTT, show modification downstream of this domain, and demonstrate that HTT is
      modified by the stress-inducible SUMO-2. A systematic study of E3 SUMO ligases
      demonstrates that PIAS1 is an E3 SUMO ligase for both HTT SUMO-1 and SUMO-2
      modification and that reduction of dPIAS in a mutant HTT Drosophila model is
      protective. SUMO-2 modification regulates accumulation of insoluble HTT in HeLa
      cells in a manner that mimics proteasome inhibition and can be modulated by
      overexpression and acute knockdown of PIAS1. Finally, the accumulation of SUMO-2
      modified proteins in the insoluble fraction of HD postmortem striata implicates
      SUMO-2 modification in the age-related pathogenic accumulation of mutant HTT and
      other cellular proteins that occurs during HD progression. 

PMID- 23871676
TI  - Usefulness of losartan on the size of the ascending aorta in an unselected cohort
      of children, adolescents, and young adults with Marfan syndrome.
AB  - Since 2008, when angiotensin II type I receptor blockade with losartan was
      introduced in the prevention of cardiovascular manifestation of Marfan syndrome
      (MFS), a specific treatment to address the cardiovascular lesions became
      available. The present study aimed to compare the response of such in an
      unselected cohort of patients with genotyped MFS. At a tertiary university
      children's hospital, 20 pediatric and adolescent patients aged 1.7 to 21.6 years
      with genetically proven MFS were enrolled in a prospective treatment study of
      losartan for evaluation of the aortic dimensions and elasticity indexes. The mean
      follow-up period was 33 +/- 11 months. A significant reduction in the normalized
      aortic dimensions with losartan was observed in the valve, root, sinotubular
      junction, and ascending aortic segments (p = 0.008, p <0.001, p = 0.012, and p =
      0.001, respectively). No correlation between elasticity behavior and the decrease
      in the aortic dimension with losartan therapy was detectable. A significant
      correlation between stronger improvement and younger age at onset (r = 0.643, p =
      0.002) and a longer therapy duration (r = -0.532, p = 0.016) was verifiable.
      However, no correlation between improvement with therapy and the type of mutation
      or presentation of clinical forms was remarkable. Elasticity also seemed to
      improve but not significantly. In conclusion, in our cohort of young patients
      with MFS, a significant improvement with losartan monotherapy was proved in all
      affected proximal aortic segments, with a better response to therapy when started
      at an earlier age and with a longer therapy duration.

PMID- 23871677
TI  - Early identification of cardiovascular involvement in patients with beta
      thalassemia major.
AB  - The aim of the present study was to evaluate left ventricular myocardial
      deformation and carotid arterial stiffness using 2-dimensional strain and echo
      tracking in patients with asymptomatic beta-thalassemia major (beta-TM) without
      significant myocardial iron overload to determine whether early subclinical
      cardiovascular abnormalities would be detectable. We enrolled 32 patients with
      beta-TM (23 women, mean age 35 +/- 8 years) and 33 healthy volunteers (20 women,
      mean age 35 +/- 6 years). All subjects underwent echocardiography with 2
      dimensional strain analysis (XStrain) and ultrasonography of the carotid arteries
      with measurement of the stiffness parameters (ProSound Alpha 10). Cardiac
      magnetic resonance imaging using a T2* algorithm (37.7 +/- 5.6 ms) for the
      assessment of myocardial iron overload was performed in each patient. The
      clinical and standard echocardiographic parameters were comparable between the
      patients and healthy subjects. The global left ventricular longitudinal strain
      was significantly impaired in the patients compared with the controls (-17.9 +/-
      3.5% vs -24.3 +/- 3.4%, p = 0.002), although the radial and circumferential
      strain values were similar between the 2 groups (p = NS for both). The carotid
      intima-media thickness was comparable between the patients and healthy subjects
      (0.67 +/- 0.20 mm vs 0.66 +/- 0.15 mm, p = NS). In contrast, the arterial
      stiffness was significantly increased in the patients compared with the controls
      (stiffness index 6.16 +/- 1.31 vs 4.65 +/- 0.82, p <0.001; arterial compliance
      1.10 +/- 0.26 vs 1.28 +/- 0.30 cm(2)/mm Hg, p = 0.027; elastic modulus 74.1 +/-
      19.5 vs 59.1 +/- 12.1 mm Hg, p = 0.001). In conclusion, cardiovascular
      abnormalities, although often subclinical, occur at an early stage of beta-TM and
      also in the absence of significant iron overload. Thus, 2-dimensional strain and
      echo-tracking might be more accurate than standard echocardiography and vascular
      parameters in the early identification of cardiovascular involvement. 

PMID- 23871678
TI  - Lawsonia intracellularis infection and proliferative enteropathy in foals.
AB  - Equine proliferative enteropathy (EPE) is a disease of foals caused by the
      obligate intracellular organism Lawsonia intracellularis. This organism is unique
      in that it causes proliferation of infected enterocytes, resulting in thickening
      of the intestinal epithelium, most often the small intestine. This disease
      affects mainly weanling foals and causes fever, lethargy, peripheral edema,
      diarrhea, colic and weight loss. The diagnosis of EPE may be challenging and
      relies on the presence of hypoproteinemia, thickening of segments of the small
      intestinal wall observed on abdominal ultrasonography, positive serology and
      molecular detection of L. intracellularis in feces. The epidemiology and genetic
      basis for pathogenesis for this disease is beginning to be elucidated. Phenotypic
      traits, genomic features, and gene expression profiles during L. intracellularis
      infection in vitro and in vivo are presented. In addition, this article reviews
      the epidemiology, pathological and clinicopathological findings, diagnosis, and
      control of EPE. 

PMID- 23871679
TI  - Effect of progesterone administration on prognosis of patients with diffuse
      axonal injury due to severe head trauma.
AB  - OBJECTIVE: Severe traumatic brain injury (TBI) has a major role in mortality rate
      among the other types of trauma. The aim of this clinical study was to assess the
      effect of progesterone on the improvement of neurologic outcome in patients with
      acute severe TBI. METHODS: A total of 76 patients who had arrived within 8h of
      injury with a Glasgow Coma Score<=8 were enrolled in the study. In a randomized
      style 38 received progesterone (1mg/kg per 12h for 5 days) and 38 did not.
      RESULTS: There was a better recovery rate and GOS score for the patients who were
      given progesterone than for those in the control group in a 3-months follow-up
      period (50% vs. 21%); subgroup analysis showed a significant difference in the
      percentage of favorable outcome between the two groups with GCS of 5-8 (p=0.03).
      CONCLUSION: The use of progesterone may significantly improve neurologic outcome
      of patients suffering severe TBI up to 3 months after injury, especially those
      with 5<=GCS<=8, providing a potential benefit to the treatment of acute severe
      TBI patients. Considering this drug had no significant side effects, so
      progesterone could be used in patients with severe TBI as a neuro-protective
      drug.

PMID- 23871680
TI  - The first survival score for patients with brain metastases from small cell lung
      cancer (SCLC).
AB  - OBJECTIVE: Survival scores can help physicians select appropriate treatment for
      patients with brain metastasis. Primary tumors have different biological behavior
      justifying separate scoring systems for different tumors. In this study, a
      survival score was developed for patients with brain metastasis from SCLC.
      METHODS: Data of 172 patients receiving whole-brain radiotherapy alone for brain
      metastasis from SCLC were included. Patients were assigned to a test (N=86) or a
      validation group (N=86). In the test group, Karnofsky Performance Score, number
      of brain metastases, and extracranial metastasis were associated with survival
      and included in the score. Scores for each factor were obtained from the 6-month
      survival rate divided by 10. According to the total scores, which represented the
      sum of the three scores, three prognostic groups were formed. RESULTS: 6-Month
      survival rates in the test group were 3% for 5-8 points, 40% for 9-12 points, and
      89% for 15 points (p<0.001). In the validation group, 6-month survival rates were
      3%, 41%, and 89% (p<0.001). The comparisons between the three prognostic groups
      of the test group and the validation group did not show significant differences.
      CONCLUSIONS: This new score appears valid and reproducible. It can be used to
      personalize the treatment to patients with brain metastasis from SCLC.

PMID- 23871682
TI  - Privacy-preserving Kruskal-Wallis test.
AB  - Statistical tests are powerful tools for data analysis. Kruskal-Wallis test is a
      non-parametric statistical test that evaluates whether two or more samples are
      drawn from the same distribution. It is commonly used in various areas. But
      sometimes, the use of the method is impeded by privacy issues raised in fields
      such as biomedical research and clinical data analysis because of the
      confidential information contained in the data. In this work, we give a privacy
      preserving solution for the Kruskal-Wallis test which enables two or more parties
      to coordinately perform the test on the union of their data without compromising
      their data privacy. To the best of our knowledge, this is the first work that
      solves the privacy issues in the use of the Kruskal-Wallis test on distributed
      data. 

PMID- 23871681
TI  - Pharmacokinetic modelling of the anti-malarial drug artesunate and its active
      metabolite dihydroartemisinin.
AB  - A four compartment mechanistic mathematical model is developed for the
      pharmacokinetics of the commonly used anti-malarial drug artesunate and its
      principle metabolite dihydroartemisinin following oral administration of
      artesunate. The model is structurally unidentifiable unless additional
      constraints are imposed. Combinations of mechanistically derived constraints are
      considered to assess their effects on structural identifiability and on model
      fits. Certain combinations of the constraints give rise to locally or globally
      identifiable model structures. Initial validation of the model under various
      combinations of the constraints leading to identifiable model structures was
      performed against a dataset of artesunate and dihydroartemisinin concentration
      time profiles of 19 malaria patients. When all the discussed constraints were
      imposed on the model, the resulting globally identifiable model structure was
      found to fit reasonably well to those patients with normal drug absorption
      profiles. However, there is wide variability in the fitted parameters and further
      investigation is warranted. 

PMID- 23871683
TI  - Automatic segmentation of corpus callosum using Gaussian mixture modeling and
      Fuzzy C means methods.
AB  - This paper presents a comparative study of the success and performance of the
      Gaussian mixture modeling and Fuzzy C means methods to determine the volume and
      cross-sectionals areas of the corpus callosum (CC) using simulated and real MR
      brain images. The Gaussian mixture model (GMM) utilizes weighted sum of Gaussian
      distributions by applying statistical decision procedures to define image
      classes. In the Fuzzy C means (FCM), the image classes are represented by certain
      membership function according to fuzziness information expressing the distance
      from the cluster centers. In this study, automatic segmentation for midsagittal
      section of the CC was achieved from simulated and real brain images. The volume
      of CC was obtained using sagittal sections areas. To compare the success of the
      methods, segmentation accuracy, Jaccard similarity and time consuming for
      segmentation were calculated. The results show that the GMM method resulted by a
      small margin in more accurate segmentation (midsagittal section segmentation
      accuracy 98.3% and 97.01% for GMM and FCM); however the FCM method resulted in
      faster segmentation than GMM. With this study, an accurate and automatic
      segmentation system that allows opportunity for quantitative comparison to
      doctors in the planning of treatment and the diagnosis of diseases affecting the
      size of the CC was developed. This study can be adapted to perform segmentation
      on other regions of the brain, thus, it can be operated as practical use in the
      clinic. 

PMID- 23871684
TI  - Impacts of variation in the human genome on gene regulation.
AB  - Recent advances in fast and inexpensive DNA sequencing have enabled the extensive
      study of genomic and transcriptomic variation in humans. Human genomic variation
      is composed of sequence and structural changes including single-nucleotide and
      multinucleotide variants, short insertions or deletions (indels), larger copy
      number variants, and similarly sized copy neutral inversions and translocations.
      It is now well established that any two genomes differ extensively and that
      structural changes constitute a prominent source of this variation. There have
      also been major technological advances in RNA sequencing to globally quantify and
      describe diversity in transcripts. Large consortia such as the 1000 Genomes
      Project and the ENCODE (ENCyclopedia Of DNA Elements) Project are producing
      increasingly comprehensive maps outlining the regions of the human genome
      containing variants and functional elements, respectively. Integration of genetic
      variation data and extensive annotation of functional genomic elements, along
      with the ability to measure global transcription, allow the impacts of genetic
      variants on gene expression to be resolved. There are several well-established
      models by which genetic variants affect gene regulation depending on the type,
      nature, and position of the variant with respect to the affected genes. These
      effects can be manifested in two ways: changes to transcript sequences and
      isoforms by coding variants, and changes to transcript abundance by dosage or
      regulatory variants. Here, we review the current state of how genetic variations
      impact gene regulation locally and globally in the human genome. 

PMID- 23871685
TI  - Acyl transfer from membrane lipids to peptides is a generic process.
AB  - The generality of acyl transfer from phospholipids to membrane-active peptides
      has been probed using liquid chromatography-mass spectrometry analysis of peptide
      lipid mixtures. The peptides examined include melittin, magainin II, PGLa, LAK1,
      LAK3 and penetratin. Peptides were added to liposomes with membrane lipid
      compositions ranging from pure phosphatidylcholine (PC) to mixtures of PC with
      phosphatidylethanolamine, phosphatidylserine or phosphatidylglycerol. Experiments
      were typically conducted at pH7.4 at modest salt concentrations (90 mM NaCl). In
      favorable cases, lipidated peptides were further characterized by tandem mass
      spectrometry methods to determine the sites of acylation. Melittin and magainin
      II were the most reactive peptides, with significant acyl transfer detected under
      all conditions and membrane compositions. Both peptides were lipidated at the N
      terminus by transfer from PC, phosphatidylethanolamine, phosphatidylserine or
      phosphatidylglycerol, as well as at internal sites: lysine for melittin; serine
      and lysine for magainin II. Acyl transfer could be detected within 3h of melittin
      addition to negatively charged membranes. The other peptides were less reactive,
      but for each peptide, acylation was found to occur in at least one of the
      conditions examined. The data demonstrate that acyl transfer is a generic process
      for peptides bound to membranes composed of diacylglycerophospholipids.
      Phospholipid membranes cannot therefore be considered as chemically inert toward
      peptides and by extension proteins.

PMID- 23871687
TI  - Early evolutionary acquisition of stomatal control and development gene
      signalling networks.
AB  - Fossil stomata of early vascular land plants date back over 418 million years and
      exhibit properties suggesting that they were operational, including
      differentially thickened guard cells and sub-stomatal chambers. Molecular studies
      on basal land plant groups (bryophytes and lycophytes) provide insight into the
      core genes involved in sensing and translating changes in the drought hormone
      abscisic acid (ABA), light and concentration of CO2 into changes in stomatal
      aperture. These studies indicate that early land plants probably possessed the
      genetic tool kits for stomata to actively respond to environmental/endogenous
      cues. With these ancestral molecular genetic tool kits in place, stomatal
      regulation of plant carbon and water relations may have became progressively more
      effective as hydraulic systems evolved in seed plant lineages. Gene expression
      and cross-species gene complementation studies suggest that the pathway
      regulating stomatal fate may also have been conserved across land plant
      evolution. This emerging area offers a fascinating glimpse into the potential
      genetic tool kits used by the earliest vascular land plants to build and operate
      the stomata preserved in the fossil record. 

PMID- 23871688
TI  - Biomolecular analysis with microring resonators: applications in multiplexed
      diagnostics and interaction screening.
AB  - Microring optical resonators are a promising class of sensor whose value in
      bioanalytical applications has only begun to be explored. Utilized in the
      telecommunication industry for signal processing applications, microring
      resonators have more recently been re-tasked for biosensing because of their
      scalability, sensitivity, and versatility. Their sensing modality arises from
      light/matter interactions--light propagating through the microring and the
      resultant evanescent field extending beyond the structure is sensitive to the
      refractive index of the local environment, which modulates resonant wavelength of
      light supported by the cavity. This sensing capability has recently been utilized
      for the detection of numerous biological targets including proteins, nucleic
      acids, viruses, and small molecules. Herein we highlight some of the most
      exciting recent uses of this technology for biosensing applications, with an eye
      towards future developments in the field.

PMID- 23871689
TI  - Simulation of transport and extravasation of nanoparticles in tumors which
      exhibit enhanced permeability and retention effect.
AB  - Determining the factors that influence the delivery of sub-micron particles to
      tumors and understanding the relative importance of each of these factors is
      fundamental to the optimization of the particle delivery process. In this paper,
      a model that combines random walk with the pressure driven movement of
      nanoparticles in a tumor vasculature is presented. Nanoparticle movement in a
      cylindrical tube with dimensions similar to the tumor's blood capillary with a
      single pore is simulated. Nanoparticle velocities are calculated as a pressure
      driven flow over imposed to Brownian motion. The number and percentage of
      nanoparticles leaving the blood vessel through a single pore is obtained as a
      function of pore size, nanoparticle size and concentration, interstitial
      pressure, and blood pressure. The model presented here is able to determine the
      importance of these controllable parameters and thus it can be used to understand
      the process and predict the best conditions for nanoparticle-based treatment. The
      results indicate that the nanoparticle delivery gradually increases with pore
      size and decreases with nanoparticle size for tumors with high interstitial fluid
      pressure (in this work we found this behavior for head and neck carcinoma and for
      metastatic melanoma with interstitial pressures of 18mmHg and 19mmHg,
      respectively). For tumors with lower interstitial fluid pressure (rectal
      carcinoma with 15.3mmHg) however, delivery is observed to have little sensitivity
      to particle size for almost the entire nanoparticle size range. Though an
      increase in nanoparticle concentration increases the number of nanoparticles
      being delivered, the efficiency of the delivery (percentage of nanoparticles
      delivered) is found to remain closely unaffected. 

PMID- 23871686
TI  - Molecular mechanisms of disease-causing missense mutations.
AB  - Genetic variations resulting in a change of amino acid sequence can have a
      dramatic effect on stability, hydrogen bond network, conformational dynamics,
      activity and many other physiologically important properties of proteins. The
      substitutions of only one residue in a protein sequence, so-called missense
      mutations, can be related to many pathological conditions and may influence
      susceptibility to disease and drug treatment. The plausible effects of missense
      mutations range from affecting the macromolecular stability to perturbing
      macromolecular interactions and cellular localization. Here we review the
      individual cases and genome-wide studies that illustrate the association between
      missense mutations and diseases. In addition, we emphasize that the molecular
      mechanisms of effects of mutations should be revealed in order to understand the
      disease origin. Finally, we report the current state-of-the-art methodologies
      that predict the effects of mutations on protein stability, the hydrogen bond
      network, pH dependence, conformational dynamics and protein function. 

PMID- 23871690
TI  - Voice controlled wheelchairs: fine control by humming.
AB  - People without disabilities seamlessly control devices with their hands.
      Interestingly, their hands can perform coarse and fine control. Implementing
      smooth control for computerized systems is not straightforward and most of the
      time it is not intuitive either. Here we offer a solution to that problem: smooth
      control through humming. Voice commands have become ubiquitous in modern
      technology. Speech-to-text applications abound. Smooth control, on the other
      hand, has not been tackled yet. Here we design and implement a humming control
      technique, and demonstrate a hardware implementation with a powered wheelchair.
      Once actuated, the speed with which the chair moves will depend on the subtle
      variation on the fundamental frequency of the user's humming, acquired through an
      accelerometer measuring vocal cord vibration. We also discuss two signal
      processing techniques that handle commonly encountered issues when trying to
      resolve frequencies in real time data. The hardware implementation shows
      performance of 80% and higher in speech recognition for signal-to-noise ratio
      (SNR) higher than 8dB and 100% in smooth control and frequency detection for all
      tested SNRs. We also discuss potential applications of smooth humming control to
      other assistive technology. 

PMID- 23871691
TI  - pocrm: an R-package for phase I trials of combinations of agents.
AB  - This paper presents the R package pocrm for implementing and simulating the
      partial order continual reassessment method (PO-CRM; [1,2]) in Phase I trials of
      combinations of agents. The aim of this article is to illustrate, through
      examples of the pocrm package, how the PO-CRM works and how its operating
      characteristics can inform clinical trial investigators. This should promote the
      use of the PO-CRM in designing and conducting dose-finding Phase I trials of
      combinations of agents. 

PMID- 23871692
TI  - Ala-7, His-10 and Arg-12 are crucial amino acids for activity of a synthetically
      engineered MU-conotoxin.
AB  - Cone snail toxins or conotoxins are often small cysteine-rich peptides which have
      shown to be highly selective ligands for a wide range of ion channels such as
      voltage-gated sodium channels (Na(V)s). Na(V)s participate in a wide range of
      electrophysiological processes. Consequently, their malfunction has been
      associated with numerous diseases. The development of subtype-selective
      modulators of Na(V)s remains highly important in the treatment of such disorders.
      In order to expand our knowledge in the search for novel therapeutics to treat
      Na(V)-related diseases, we explored the field of peptide engineering. In the
      current study, the impact of well considered point mutations into a bioactive
      peptide that was found to be a very potent and selective inhibitor of Na(V)s
      (i.e. Midi R2) was examined. We designed two peptides, named Midi R2[A7G] and
      Midi R2[H10A, R12A] which have mutations at position 7, and both 10 and 12,
      respectively. Electrophysiological recordings indicated that an Ala to Gly
      mutation at position 7 increased IC50-values from the nanomolar range to the
      micromolar range. For Midi R2[H10A, R12A] at a concentration of 10 MUM, activity
      is even reduced to 0-10% for all of the tested Na(V)-channels. Circular dichroism
      measurements proved that overall structural conformations did not change. These
      findings suggest that the minimal space between the second and the third
      intercysteine loop of Midi R2 is the sequence RRWARDHSR and that His at position
      10 and Arg at position 12 are crucial amino acids for the potency and specificity
      of Midi R2. In this way, new insights into the structure-activity relationships
      of MU-conotoxins were found.

PMID- 23871693
TI  - Gamma-melanocyte stimulating hormone regulates the expression and cellular
      localization of epithelial sodium channel in inner medullary collecting duct
      cells.
AB  - Gamma(2)-melanocyte-stimulating hormone (gamma2MSH) is a peptide hormone released
      by the pituitary gland which is thought to act directly on the renal inner
      medulla to promote increased sodium excretion into urine (natriuresis). The aim
      of this study was to determine if a stable analog, [Nle(3), D-Phe(6)]-gamma2MSH
      (NDP-gamma2MSH), of the native peptide regulated the activity, expression and
      cellular localization of epithelial sodium channel (ENaC) in a murine inner
      medullary collecting duct (mIMCD-3) cell line. Our results indicate that
      expression of the gamma2MSH receptor, melanocortin receptor 3 receptor (MC3R), is
      up-regulated by culturing the cells in media with an increased osmolality
      (~400mOsm/kg). Furthermore, stimulation of cAMP signaling and sodium transport by
      1nM NDP-gamma2MSH occurs only in cells cultured in the high osmolality media.
      Finally, treatment of mIMCD-3 cells cultured in high osmolality medium for 1h
      with 1nM NDP-gamma2MSH causes a reduction in expression of serum- and
      glucocorticoid-induced kinase (sgk1) and a reduction in expression and cell
      surface abundance of the alpha subunit of ENaC. Collectively, this data suggest
      that gamma2MSH directly regulates both ENaC expression and cellular localization
      in the inner medulla to exert its natriuretic effect.

PMID- 23871694
TI  - Natural history of tunneled dialysis catheters placed for hemodialysis
      initiation.
AB  - PURPOSE: More than 80% of hemodialysis recipients in the United States initiate
      hemodialysis with a tunneled dialysis catheter (TDC). Published data on TDC
      outcomes are based on a case mix of prevalent and incident TDCs. The present
      study analyzes factors affecting patency and complications of first TDCs placed
      in a large cohort of incident hemodialysis recipients. MATERIALS AND METHODS: A
      prospective, computerized vascular access database was retrospectively queried to
      identify 472 patients receiving a first-ever TDC. Multiple-variable survival
      analysis was used to identify clinical parameters affecting TDC patency (from
      placement to nonelective removal) and infection (from placement to first episode
      of catheter-related bacteremia [CRB]). RESULTS: The median patency of all TDCs
      was 202 days. Left-sided placement of TDCs was the only variable associated with
      inferior TDC patency (hazard ratio, 1.98; 95% confidence interval, 1.39-2.81; P <
      .0001). The 6-month TDC patency rate was 37% for left internal jugular vein
      (LIJV) catheters, versus 54% for right internal jugular vein (RIJV) catheters.
      The 1-year patency rate was 6% for LIJV catheters, versus 35% for RIJV catheters.
      Catheter patency was not associated with patient age, sex, race, hypertension,
      diabetes, coronary artery disease, peripheral vascular disease, cerebrovascular
      disease, or heart failure. The median time to the first episode of CRB was 163
      days. None of the clinical variables was associated with TDC infection.
      CONCLUSIONS: TDCs are plagued by high rates of infection. RIJV TDCs should be
      used preferentially to maximize catheter patency.

PMID- 23871695
TI  - Embolization of angiographically visible type I and II utero-ovarian anastomoses
      during uterine artery embolization for fibroid tumors: impact on symptom
      recurrence and permanent amenorrhea.
AB  - PURPOSE: To compare the incidences of symptom recurrence and permanent amenorrhea
      following uterine artery embolization (UAE) for symptomatic fibroid tumors in
      patients with type I and II utero-ovarian anastomoses (UOAs) with versus without
      ovarian artery embolization (OAE). MATERIALS AND METHODS: A retrospective,
      institutional review board-approved study of 99 women who underwent UAE for
      symptomatic fibroid tumors from April 2005 to October 2010 was conducted to
      identify patients who had type I or II UOAs at the time of UAE. Based on the
      embolization technique, patients were categorized into standard (ie, UAE only),
      combined (ie, UAE and OAE), and control (patients without UOAs who underwent UAE)
      groups. Data collected included patient characteristics, procedural technique and
      findings, symptom recurrence, secondary interventions, and permanent amenorrhea.
      Statistical analysis was performed with the Fisher exact test, with significance
      reached at P < .05. RESULTS: Twenty patients (20.2%; mean age, 46.9 y +/- 6.3)
      had type I (n = 3) or II (n = 17) UOAs. Thirteen (65%) underwent UAE only
      (standard group) and seven (35%) underwent UAE and OAE (combined group). There
      were no significant differences between groups in demographics or in the
      incidence of permanent amenorrhea after procedures (follow-up, 561 d +/- 490).
      There was a significantly higher incidence of symptom recurrence in the standard
      group compared with the control group (P = .01), with no differences between
      combined and control groups (P = 1). CONCLUSIONS: There were no statistical
      differences in permanent amenorrhea rates in the groups studied, with
      significantly higher symptom recurrence rates observed when OAE was not performed
      in the setting of UOA.

PMID- 23871697
TI  - In utero exposure to nanosized carbon black (Printex90) does not induce tandem
      repeat mutations in female murine germ cells.
AB  - Inhalation of particles has been shown to induce mutations in the male germline
      in mice following both prenatal and adult exposures in several experiments. In
      contrast, the effects of particles on female germ cell mutagenesis are not well
      established. Germline mutations are induced during active cell division, which
      occurs during fetal development in females. We investigated the effects of
      prenatal exposure to carbon black nanoparticles (CB) on induction of mutations in
      the female mouse germline during fetal development, spanning the critical
      developmental stages of oogenesis. Pregnant C57BL/6J mice were exposed four times
      during gestation by intratracheal instillation of 67MUg/animal of nanosized
      carbon black Printex90 or vehicle (gestation days 7, 10, 15 and 18). Female
      offspring were raised to maturity and mated with unexposed CBA males. Expanded
      simple tandem repeat (ESTR) germline mutation rates in the resulting F2
      generation were determined from full pedigrees (mother, father, offspring) of F1
      female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in
      CB-exposed F2 female offspring were not statistically different from those of F2
      female control offspring. 

PMID- 23871696
TI  - KDM4A lysine demethylase induces site-specific copy gain and rereplication of
      regions amplified in tumors.
AB  - Acquired chromosomal instability and copy number alterations are hallmarks of
      cancer. Enzymes capable of promoting site-specific copy number changes have yet
      to be identified. Here, we demonstrate that H3K9/36me3 lysine demethylase
      KDM4A/JMJD2A overexpression leads to localized copy gain of 1q12, 1q21, and
      Xq13.1 without global chromosome instability. KDM4A-amplified tumors have
      increased copy gains for these same regions. 1q12h copy gain occurs within a
      single cell cycle, requires S phase, and is not stable but is regenerated each
      cell division. Sites with increased copy number are rereplicated and have
      increased KDM4A, MCM, and DNA polymerase occupancy. Suv39h1/KMT1A or HP1gamma
      overexpression suppresses the copy gain, whereas H3K9/K36 methylation
      interference promotes gain. Our results demonstrate that overexpression of a
      chromatin modifier results in site-specific copy gains. This begins to establish
      how copy number changes could originate during tumorigenesis and demonstrates
      that transient overexpression of specific chromatin modulators could promote
      these events. 

PMID- 23871698
TI  - Glycosylated hemoglobin for diagnosis of prediabetes in acute ischemic stroke
      patients.
AB  - BACKGROUND: Prediabetes (PD) is an independent risk factor for stroke. The
      American Diabetes Association (ADA) has recently published new guidelines
      recommending glycosylated hemoglobin A1c (HbA1c) as a marker to diagnose diabetes
      and PD. Diagnosis of diabetes Mellitus (DM) is often made at the time of
      hospitalization for stroke. Less is known about identifying PD in acute ischemic
      stroke (AIS) patients. We aim to investigate the frequency of new-onset PD in the
      hospitalized AIS patients using the new ADA guidelines. METHODS: We
      retrospectively studied 362 AIS patients from our local database. Stroke risk
      factors, type of stroke, and white matter hyperintensities (WMHs) were all
      collected. Based on the 2010 ADA guidelines, patients were classified as
      prediabetics, with HbA1c levels of 5.7%-6.4%; diabetics, with HbA1c levels more
      than 6.5%; and normoglycemic, HbA1c levels less than 5.7%. We used SAS 9.3 for
      analysis. RESULTS: On admission, 279 (78%) AIS patients had HbA1c values
      collected. Stratifying by HbA1c, 113 (31%) AIS patients were given the diagnosis
      of DM and 109 (30%) were given the diagnosis of PD. From the 166 patients with no
      DM history, 53% had PD and 15% had DM. Patients with DM and PD were more likely
      to have hypertension (P<.001) and hyperlipidemia (P=.05). The likelihood of new
      onset PD increased with age (P<.01). No differences were found by the type of
      stroke or WMH. CONCLUSION: Diabetes and PD are highly prevalent in the
      hospitalized ischemic stroke (IS) patients. Our results suggest a need for
      routine HbA1c testing in all patients with IS. Further larger studies need to
      confirm these findings.

PMID- 23871699
TI  - Adult height and body mass index in relation to risk of total stroke and its
      subtypes: the circulatory risk in communities study.
AB  - BACKGROUND: Several studies have reported that height and risk of stroke are
      inversely associated based on the hypothesis that height is a marker of childhood
      physical condition. However, a limited number of studies have taken account of
      the effect of current physical condition on the relationship between height and
      risk of stroke. METHODS: We conducted a prospective cohort study of 12,222 40- to
      69-year-old Japanese patients under systematic surveillance for stroke incidence.
      Because body mass index (BMI) is regarded as a surrogate marker of current
      physical condition for cardiovascular risk, we performed a stratified analysis of
      this risk based on BMI. RESULTS: During the median 17-year follow-up, there were
      565 incident strokes (326 ischemic and 186 hemorrhagic strokes) showing an
      inverse association between height and risk of stroke independent of classical
      cardiovascular risk factors. Compared with the lowest height group (<159 cm for
      men and <148 cm for women) as reference, the multivariable hazard ratios (HRs)
      and 95% confidence intervals (95% CIs) for the highest height group (>166 cm for
      men and >154 cm for women) were 0.70 (95% CI 0.49-1.00; P = .043) for men and
      0.44 (95% CI 0.27-0.70; P < .001) for women. When the analysis was restricted to
      those with BMI <23 kg/m(2), the associations were stronger for both hemorrhagic
      and ischemic stroke. CONCLUSIONS: Height was found to be inversely associated
      with risk of stroke for middle-aged Japanese men and women, especially with lower
      BMIs. Our findings suggest that childhood social and physical conditions may
      contribute to the development of stroke in adulthood because height is a
      surrogate marker of these conditions.

PMID- 23871700
TI  - Higher frequency of atrial fibrillation linked to colder seasons and air
      temperature on the day of ischemic stroke onset.

PMID- 23871701
TI  - Clinical outcomes after intravenous fibrinolysis in cryptogenic strokes with or
      without patent foramen ovale.
AB  - BACKGROUND: Pivotal clinical trials suggest that intravenous (IV) recombinant
      tissue plasminogen activator (rt-PA) benefits stroke patients regardless of the
      underlying etiology. Paradoxical strokes, presumed to be caused by fibrin-rich
      clots originating in the venous circulation, may respond better to fibrinolysis
      than other ischemic stroke subtypes. In this study, we compared the response with
      IV rt-PA in paradoxical stroke patients and other stroke subtypes. METHODS: In
      total, 486 patients treated with IV rt-PA at a single institution were
      retrospectively reviewed. Adjudication of stroke mechanism was based on chart
      review. Five major stroke mechanisms--cardioembolic, artery-to-artery emboli,
      lacunar, cryptogenic, and paradoxical--were identified by final diagnosis from
      chart reviews. Mimics, undefined etiology, and defined etiology not falling into
      the major mechanisms were excluded. Analysis of variance and general linear model
      were used to assess the differences between groups. RESULTS: A total of 323
      patients were analyzed. We found significant differences in clinical outcome
      between stroke mechanisms, including discharge National Institutes of Health
      Stroke Scale (NIHSS) (P=.007), discharge Rankin (P=.011), discharge disposition
      (P=.000), and infarct volume (P=.007). Post hoc analysis showed that
      cardioembolic patients had the worst outcomes (discharge NIHSS score 11.12+/
      12.26), whereas paradoxical strokes had the best outcomes (discharge NIHSS score
      3.67+/-4.90), but these did not approach statistical significance. However,
      regression analysis showed that 4 variables--congestive heart failure, admission
      NIHSS, age, and mean infarct volume--rather than stroke mechanism were the true
      predictors of poor outcome. CONCLUSIONS: Paradoxical strokes had better outcomes
      after IV fibrinolysis than other ischemic stroke subtypes, but this difference is
      attributable to younger age and milder stroke severity on presentation.

PMID- 23871703
TI  - Patient-physician distance.

PMID- 23871702
TI  - Trends in antihypertensive drug prescription patterns among ambulatory stroke
      patients in the United States, 2000-2009.
AB  - BACKGROUND: Although the ambulatory setting is recognized as the best arena for
      optimizing antihypertensive drug treatment after a stroke, little is known about
      recent office-based antihypertensive drug treatment patterns in the United
      States. We assessed national trends in antihypertensive treatment for stroke
      patients in office-based medical practice. METHODS: Data from the 2000-2009
      National Ambulatory Medical Care Surveys were analyzed comprising outpatient
      visits to physicians in office-based practice by patients aged 40 years or older
      with a diagnosis of stroke (weighted estimate=46,317,269). The main outcome
      measure was visits with a prescription of antihypertensive medication(s).
      RESULTS: The proportion of total visits that included a prescription of
      antihypertensive medication was 35.6% in 2000-2002, 29.5% in 2003-2005, and 49.3%
      in 2006-2009 (P=.002); 50.9% were primary care physician (PCP) visits versus
      26.2% neurologist visits (P<.0001). Age-adjusted logistic regression analyses
      confirmed a higher prescription rate in 2006-2009 versus 2000-2002 (1.81; 95%
      confidence interval [CI], 1.10-2.96) and PCP versus neurologists (2.82; 95% CI,
      1.86-4.27). Use of 2 or more agent classes was 31.6% in 2000-2002, 44.2% in 2003
      2005, and 56.7% in 2006-2009 (P=.014). Age-adjusted logistic regression analyses
      confirmed a higher prescription rate of 2 or more agent classes in 2006-2009
      versus 2000-2002 (2.96; 95% CI, 1.40-6.24). There were no significant differences
      in agent class type or number between neurologists versus PCPs. CONCLUSIONS: Over
      the last decade, there was a significant rise in the use of antihypertensive
      drugs and combination of agent classes for patients aged 40 years or older seen
      in an ambulatory setting with a diagnosis of stroke. PCPs were more likely than
      neurologists to prescribe these agents.

PMID- 23871705
TI  - Early fatigue fractures in the IS-1 connector leg of a small-diameter ICD lead:
      value of returned product analysis for improving device safety.
AB  - BACKGROUND: Conductor fractures may affect the performance of implantable
      cardioverter-defibrillator leads. During routine surveillance of returned product
      analyses (RPAs) in the Food and Drug Administration's Manufacturers and User
      Facility Device Experience database, we found a number of conductor fractures in
      small diameter implantable cardioverter-defibrillator leads manufactured by St
      Jude Medical, Inc (SJM, Sylmar, CA). OBJECTIVES: To determine the location and
      cause of these fractures and to catalog their clinical signs and consequences.
      METHODS: We searched the FDA's Manufacturers and User Facility Device Experience
      database on April 11, 2013. SJM provided information and data it collected
      independently. RESULTS: Our search found 59 leads with fractures in the IS-1 leg.
      Most fractures were in leads implanted in 2008-2009; no fractures were found in
      leads implanted after 2010. Outer coil conductor fractures accounted for the
      majority (51 of 59, 86%). Oversensing and noise were common signs, and 81% of the
      patients received inappropriate shocks. SJM's RPAs found that the fractures were
      due to inadequate strain relief and redesigned the IS-1 leg by shortening the
      crimp bore. Younger age and subpectoral implants appeared to be associated with
      these fractures. SJM stated the incidence is low (0.040%) and has not seen
      further fractures of this type in leads with the modified crimp. CONCLUSIONS:
      SJM's small diameter leads that were manufactured before 2011 are prone to early
      outer coil fatigue fractures in the IS-1 leg. The failure mechanism appears to
      have been mitigated by a design change. RPA is important for improving device
      safety.

PMID- 23871704
TI  - Heterogeneity and function of K(ATP) channels in canine hearts.
AB  - BACKGROUND: The concept that pore-forming Kir6.2 and regulatory SUR2A subunits
      form cardiac ATP-sensitive potassium (K(ATP)) channels is challenged by recent
      reports that SUR1 is predominant in mouse atrial K(ATP) channels. OBJECTIVE: To
      assess SUR subunit composition of K(ATP) channels and consequence of K(ATP)
      activation for action potential duration (APD) in dog hearts. METHODS: Patch
      clamp techniques were used on isolated dog cardiomyocytes to investigate K(ATP)
      channel properties. Dynamic current clamp, by injection of a linear K(+)
      conductance to simulate activation of the native current, was used to study the
      consequences of K(ATP) activation on APD. RESULTS: Metabolic inhibitor (MI)
      activated current was not significantly different from pinacidil (SUR2A-specific)
      activated current, and both currents were larger than diazoxide (SUR1-specific)
      activated current in both the atrium and the ventricle. Mean K(ATP) conductance
      (activated by MI) did not differ significantly between chambers, although, within
      the ventricle, both MI-induced and pinacidil-induced currents tended to decrease
      from the epicardium to the endocardium. Dynamic current-clamp results indicate
      that myocytes with longer baseline APDs are more susceptible to injected K(ATP)
      current, a result reproduced in silico by using a canine action potential model
      (Hund-Rudy) to simulate epicardial and endocardial myocytes. CONCLUSIONS: Even a
      small fraction of K(ATP) activation significantly shortens APD in a manner that
      depends on existing heterogeneity in K(ATP) current and APD.

PMID- 23871706
TI  - Treatment of pseudotumors after metal-on-metal hip resurfacing based on magnetic
      resonance imaging, metal ion levels and symptoms.
AB  - Peri-prosthetic pseudotumor formation can be a severe complication following
      Metal-on-Metal hip resurfacing arthroplasty (MoMHRA), with limited data on the
      optimal management of this complication. The aims of this study were (1) to
      evaluate the prevalence and severity of pseudotumors in a consecutive cohort of
      248 MoMHRA (214 patients, mean follow-up 4.6 years, range: 1 - 8.2), and (2) to
      present a clinical guideline for their treatment based on severity grading with
      Metal Artefact Reduction Sequence Magnetic Resonance Imaging, metal ion levels
      and symptoms. Pseudotumor prevalence was 36.3%: 61 mild, 25 moderate and four
      were graded severe. Five revisions followed, all in symptomatic patients with
      elevated metal ion levels. Pseudotumor severity grading allowed us to be
      conservative with revision surgery for mild and moderate MoM disease.

PMID- 23871707
TI  - Extramedullary guides versus portable, accelerometer-based navigation for tibial
      alignment in total knee arthroplasty: a randomized, controlled trial: winner of
      the 2013 HAP PAUL award.
AB  - Extramedullary (EM) tibial alignment guides have demonstrated a limited degree of
      accuracy in total knee arthroplasty (TKA). The purpose of this study was to
      compare the tibial component alignment obtained using a portable, accelerometer
      based navigation device versus EM alignment guides. One hundred patients were
      enrolled in this prospective, randomized controlled study to receive a TKA using
      either the navigation device, or an EM guide. Standing AP hip-to-ankle and
      lateral knee-to-ankle radiographs were obtained at the first, postoperative
      visit. 95.7% of tibial components in the navigation cohort were within 2 degrees 
      of perpendicular to the tibial mechanical axis, versus 68.1% in the EM cohort
      (P<0.001). 95.0% of tibial components in the navigation cohort were within 2
      degrees  of a 3 degrees  posterior slope, versus 72.1% in the EM cohort
      (P=0.007). A portable, accelerometer-based navigation device decreases outliers
      in tibial component alignment compared to conventional, EM alignment guides in
      TKA. 

PMID- 23871708
TI  - Correlation of aspiration results with periprosthetic sepsis in revision total
      hip arthroplasty.
AB  - A retrospective chart review was performed of all patients who had undergone
      revision total hip arthroplasty with a synovial aspiration with greater than 100
      WBC since the institution of our electronic medical record. Infection was defined
      using a combination of criteria. A diagnosis of periprosthetic sepsis was
      established in 52 of the 253 included hips. No significant differences existed
      with respect to gender, age, BMI, Deyo-Charlson Comorbidity Index, or the cause
      of initial hip degeneration. Using receiver-operating characteristic curves
      accuracy was maximized for WBC of 745 or segmented cell count of 73.5% with a
      sensitivity of 98%, specificity of 37%, negative predictive value of 99% and
      accuracy of 50%. Application of the current American Academy of Orthopaedic
      Surgery Clinical Practice Guidelines (AAOS CPG) thresholds revealed a similar
      accuracy of 49%. 

PMID- 23871709
TI  - Prognostic role of human epidermal growth factor receptor in gastric cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Human epidermal growth factor receptor (EGFR) and HER2
      (ErbB2) both belong to EGFR family, which are overexpressed in a significant
      proportion of cases of gastric cancer (GC). Various studies have evaluated the
      prognostic value of EGFR or HER level in GC. However, the overall test
      performance remains unclear. We undertook this study to perform a systematic
      review and meta-analysis of prognostic cohort studies evaluating the use of EGFR
      or HER2 as a predictor of survival time in patients with GC. METHODS: Eligible
      studies were identified through multiple search strategies. Studies were assessed
      for quality using the Newcastle-Ottawa Tool. Data were collected comparing
      overall survival (OS) in patients with high and low EGFR or HER2 level. Studies
      were pooled and summary hazard ratios were calculated. RESULTS: Studies were
      listed twice if they provided overall survival data for both EGFR and HER2. Eight
      studies (seven for EGFR and eight for HER2) were included. Two distinct groups
      were pooled for analysis and revealed that high EGFR, HER2 levels predicted poor
      overall (HR = 1.66, 95% CI: 1.35-2.02) and (HR = 1.43, 95% CI: 1.09-1.88)
      survival. No publication bias was found. CONCLUSIONS: This meta-analysis result
      suggested that EGFR or HER2 should have significant predictive ability for
      estimating overall survival in GC patients and may be useful for defining
      prognosis of GC patients.

PMID- 23871710
TI  - Complete subsite mapping of a "loopful" GH19 chitinase from rye seeds based on
      its crystal structure.
AB  - Crystallographic analysis of a mutated form of "loopful" GH19 chitinase from rye
      seeds a double mutant RSC-c, in which Glu67 and Trp72 are mutated to glutamine
      and alanine, respectively, (RSC-c-E67Q/W72A) in complex with chitin
      tetrasaccharide (GlcNAc)4 revealed that the entire substrate-binding cleft was
      completely occupied with the sugar residues of two (GlcNAc)4 molecules. One
      (GlcNAc)4 molecule bound to subsites -4 to -1, while the other bound to subsites
      +1 to +4. Comparisons of the main chain conformation between liganded RSC-c
      E67Q/W72A and unliganded wild type RSC-c suggested domain motion essential for
      catalysis. This is the first report on the complete subsite mapping of GH19
      chitinase.

PMID- 23871711
TI  - Impact of epidermal growth factor receptor mutations on intracranial treatment
      response and survival after brain metastases in lung adenocarcinoma patients.
AB  - INTRODUCTION: Brain metastases (BM) commonly occur in patients with lung
      adenocarcinoma and usually lead to a poor prognosis and quality of life despite
      of radiotherapy. Epidermal growth factor receptor (EGFR) mutations have been
      widely demonstrated to be a predictive and prognostic factor for lung
      adenocarcinoma, however, its impact on BM from lung adenocarcinoma remains
      inconclusive. The present study aimed to elucidate the predictive role of EGFR
      mutations in BM treatment response and survival after BM in patients with lung
      adenocarcinoma. MATERIAL AND METHODS: From January 2006 through February 2012,
      180 of 505 lung adenocarcinoma patients developed BM during their disease course
      were reviewed for eligibility, and 139 patients, including 89 EGFR-mutant and 50
      EGFR wild-type patients, were identified for analysis. RESULTS: Of the patients
      eligible for evaluation of treatment response, up to 85% received radiotherapy
      and the remaining took EGFR tyrosine kinase inhibitors (TKIs) as the front
      modality for BM. EGFR-mutant patients, compared with EGFR wild-type patients, had
      significantly greater intracranial treatment response of BM (84% vs. 48%, P =
      0.002), experienced higher therapeutic efficacy to radiotherapy (86% vs. 52%, P =
      0.005), and had longer median survival after BM diagnosis (13.2 vs. 6.8 months, P
      < 0.001). Furthermore, EGFR mutation (P = 0.002) and performance status (P =
      0.009) were independently associated with BM treatment response. Additionally,
      EGFR mutation (P = 0.005), good performance status (P < 0.001) and absence of
      extracranial metastases (P=0.033) correlated with better survival. CONCLUSION:
      EGFR mutation is an independent predictive factor for both BM treatment response
      and survival after BM in patients with lung adenocarcinoma. Further prospective
      studies on incorporation of EGFR mutation status into therapeutic strategy and
      survival prediction system for lung adenocarcinoma with BM are warranted.

PMID- 23871712
TI  - Stochastic resonance in feedforward-loop neuronal network motifs in astrocyte
      field.
AB  - Elucidating the underlying dynamical properties of neuronal network motifs,
      statistically significant patterns of interconnections, is essential to
      understand the dynamics of the whole networks. Besides, the brain is
      intrinsically noisy. Various noise-induced dynamical behaviors, in particular,
      the stochastic resonance (SR), have been found in both neuronal systems and
      neuronal network motifs. However, the effect of astrocytes, active partners in
      neuronal signal processing, has not yet received much attention. In this paper,
      we study the effect of astrocytes on the stochastic behaviors of the typical
      triple-neuron feedforward-loop (FFL) neuronal network motifs. The neurons are
      described by the Hodgkin-Huxley model, while the astrocytes are modeled by
      extending the Li-Rinzel model to a two-dimensional field with the effect of
      diffusion. The mutual neuron-astrocyte interactions are established
      correspondingly. Simulation results indicate that the stochastic behaviors of the
      FFL motifs show bell-shaped dependence on the intensities of both noise and
      astrocyte-neuron coupling. Moreover, in the presence of astrocytes, the
      performance of the FFL motifs on weak signal transmission in both noisy and noise
      free environments can be significantly improved. From this point of view, the
      astrocytes can be regarded as a possible internal source of "noise", which assist
      the neurons in signal processing. 

PMID- 23871713
TI  - Efficacy of function specific 3D-motifs in enzyme classification according to
      their EC-numbers.
AB  - Due to the increasing number of protein structures with unknown function
      originated from structural genomics projects, protein function prediction has
      become an important subject in bioinformatics. Among diverse function prediction
      methods, exploring known 3D-motifs, which are associated with functional elements
      in unknown protein structures is one of the most biologically meaningful methods.
      Homologous enzymes inherit such motifs in their active sites from common
      ancestors. However, slight differences in the properties of these motifs, results
      in variation in the reactions and substrates of the enzymes. In this study, we
      examined the possibility of discriminating highly related active site patterns
      according to their EC-numbers by 3D-motifs. For each EC-number, the spatial
      arrangement of an active site, which has minimum average distance to other active
      sites with the same function, was selected as a representative 3D-motif. In order
      to characterize the motifs, various points in active site elements were tested.
      The results demonstrated the possibility of predicting full EC-number of enzymes
      by 3D-motifs. However, the discriminating power of 3D-motifs varies among
      different enzyme families and depends on selecting the appropriate points and
      features. 

PMID- 23871714
TI  - A dynamical system that describes vein graft adaptation and failure.
AB  - Adaptation of vein bypass grafts to the mechanical stresses imposed by the
      arterial circulation is thought to be the primary determinant for lesion
      development, yet an understanding of how the various forces dictate local wall
      remodeling is lacking. We develop a dynamical system that summarizes the complex
      interplay between the mechanical environment and cell/matrix kinetics, ultimately
      dictating changes in the vein graft architecture. Based on a systematic mapping
      of the parameter space, three general remodeling response patterns are observed:
      (1) shear stabilized intimal thickening, (2) tension induced wall thinning and
      lumen expansion, and (3) tension stabilized wall thickening. Notable is our
      observation that the integration of multiple feedback mechanisms leads to a
      variety of non-linear responses that would be unanticipated by an analysis of
      each system component independently. This dynamic analysis supports the clinical
      observation that the majority of vein grafts proceed along an adaptive
      trajectory, where grafts dilate and mildly thicken in response to the increased
      tension and shear, but a small portion of the grafts demonstrate a maladaptive
      phenotype, where progressive inward remodeling and accentuated wall thickening
      lead to graft failure. 

PMID- 23871715
TI  - Immunization strategies for epidemic processes in time-varying contact networks.
AB  - Spreading processes represent a very efficient tool to investigate the structural
      properties of networks and the relative importance of their constituents, and
      have been widely used to this aim in static networks. Here we consider simple
      disease spreading processes on empirical time-varying networks of contacts
      between individuals, and compare the effect of several immunization strategies on
      these processes. An immunization strategy is defined as the choice of a set of
      nodes (individuals) who cannot catch nor transmit the disease. This choice is
      performed according to a certain ranking of the nodes of the contact network. We
      consider various ranking strategies, focusing in particular on the role of the
      training window during which the nodes' properties are measured in the time
      varying network: longer training windows correspond to a larger amount of
      information collected and could be expected to result in better performances of
      the immunization strategies. We find instead an unexpected saturation in the
      efficiency of strategies based on nodes' characteristics when the length of the
      training window is increased, showing that a limited amount of information on the
      contact patterns is sufficient to design efficient immunization strategies. This
      finding is balanced by the large variations of the contact patterns, which
      strongly alter the importance of nodes from one period to the next and therefore
      significantly limit the efficiency of any strategy based on an importance ranking
      of nodes. We also observe that the efficiency of strategies that include an
      element of randomness and are based on temporally local information do not
      perform as well but are largely independent on the amount of information
      available. 

PMID- 23871716
TI  - Inhibition of glycogen synthase kinase-3beta by lithium chloride suppresses 6
      hydroxydopamine-induced inflammatory response in primary cultured astrocytes.
AB  - An increasing amount of evidence has emerged to suggest that neuroinflammatory
      process is involved in the pathogenesis of Parkinson's disease (PD). Activated
      microglia and astrocytes are found in the substantia nigra (SN) of Parkinson's
      disease brains as well as in animal models of Parkinson's disease. Although
      reactive astrocytes are involved in the progression of PD, the role of reactive
      astrocytes in neuroinflammation of PD has received limited attention to date.
      Recently, Glycogen synthase kinase-3beta (GSK-3beta) was identified as a crucial
      regulator of the inflammatory response. The purpose of this study was to explore
      the mechanism by which 6-hydroxydopamine (6-OHDA) induces inflammatory response
      in astrocytes and observe the anti-inflammatory effect of lithium chloride (LiCl)
      on 6-OHDA-treated astrocytes. In the present study, we found that glial
      fibrillary acidic protein (GFAP) was markedly upregulated in the presence of 6
      OHDA. Moreover, our results revealed that proinflammatory molecules including
      inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2(COX
      2), prostaglandins E2 (PGE2), and tumor necrosis factor-alpha (TNF-alpha) were
      obviously increased in astrocytes exposed to 6-OHDA. Western blot analysis
      revealed that 6-OHDA significantly increased dephosphorylation/activation of GSK
      3beta as well as the nuclear translocation of nuclear factor-kappaB (NF-kappaB)
      p65. Besides, GSK-3beta inhibitor LiCl and SB415286 inhibited the GSK-3beta/NF
      kappaB signaling pathway, leading to the reduction of proinflammatory molecules
      in 6-OHDA-activated astrocytes. These results confirmed that GSK-3beta inhibitor
      LiCl and SB415286 provide protection against neuroinflammation in 6-OHDA-treated
      astrocytes. Therefore, GSK-3beta may be a potential therapeutic target for the
      treatment of PD. 

PMID- 23871717
TI  - Protective effect of nebivolol on reserpine-induced neurobehavioral and
      biochemical alterations in rats.
AB  - Reserpine-induced orofacial dyskinesia is a model that shares some mechanists'
      aspects with tardive dyskinesia whose pathophysiology has been related to
      oxidative stress. The present study was aimed to explore neuroprotective effects
      of nebivolol, an antihypertensive agent, on reserpine-induced neurobehavioral and
      biochemical alterations in rats. Reserpine (1mg/kg, s.c.) was used to induce
      neurotoxicity. Administration of reserpine for 3 days every other day
      significantly increased the vacuous chewing movements (VCMs), tongue protrusions
      (TPs) and reduced the locomotor activity in rats. Pre-treatment with nebivolol (5
      and 10mg/kg, p.o. for 5 days) showed dose dependant decrease in VCMs and TP
      induced by reserpine. Nebivolol also showed significant improvement in locomotor
      activity. Reserpine significantly increased lipid peroxidation and reduced the
      levels of defensive antioxidant enzymes like catalase (CAT), superoxide dismutase
      (SOD) and reduced glutathione (GSH) in rat brain. Nebivolol reversed these
      effects of reserpine on oxidative stress indices; indicating amelioration of
      oxidative stress in rat brains. The results of the present study indicated that
      nebivolol has a protective role against reserpine-induced orofacial dyskinesia.
      Thus, the use of nebivolol as a therapeutic agent for the treatment of tardive
      dyskinesia may be considered.

PMID- 23871718
TI  - Influence of a long-term powdered diet on the social interaction test and
      dopaminergic systems in mice.
AB  - It is well known that the characteristics of mastication are important for the
      maintenance of our physical well-being. In this study, to assess the importance
      of the effects of food hardness during mastication, we investigated whether a
      long-term powdered diet might cause changes in emotional behavior tests,
      including spontaneous locomotor activity and social interaction (SI) tests, and
      the dopaminergic system of the frontal cortex and hippocampus in mice. Mice fed a
      powdered diet for 17 weeks from weaning were compared with mice fed a standard
      diet (control). The dopamine turnover and expression of dopamine receptors mRNA
      in the frontal cortex were also evaluated. Spontaneous locomotor activity, SI
      time and dopamine turnover of the frontal cortex were increased in powdered diet
      fed mice. On the other hand, the expression of dopamine-4 (D4) receptors mRNA in
      the frontal cortex was decreased in powdered diet-fed mice. Moreover, we examined
      the effect of PD168077, a selective D4 agonist, on the increased SI time in
      powdered diet-fed mice. Treatment with PD168077 decreased the SI time. These
      results suggest that the masticatory dysfunction induced by long-term powdered
      diet feeding may cause the increased SI time and the changes in the dopaminergic
      system, especially dopamine D4 receptor subtype in the frontal cortex.

PMID- 23871719
TI  - An evolving paradigm for the workup and management of high-risk cutaneous
      squamous cell carcinoma.
AB  - BACKGROUND: No established standard of care exists for aggressive cutaneous
      squamous cell carcinoma (CSCC). OBJECTIVE: We sought to establish an aggressive
      CSCC management protocol by reviewing high-risk CSCC (HCSCC) and very high-risk
      CSCC (VCSCC) cases at our institution. METHODS: This was a retrospective review
      of all CSCC cases treated at our institution. RESULTS: A total of 27 patients
      were identified of 1591 cases treated between 2000 and 2011. Four patients with
      HCSCC received surgery alone and 1 received surgery and radiation. All remain
      disease free (median follow-up 5 years). Among patients with VCSCC, 4 received
      surgery alone: 1 (25%) showing a complete response and 3 (75%) showing disease
      progression. Eleven received surgery and radiation: 4 (36.4%) with complete
      response (median follow-up 3 years) and 7 (63.6%) with disease progression
      (median time to recurrence 6 months). Six received surgery and cetuximab: 3 (50%)
      had a complete response (median follow-up 3 years), 2 (33%) had disease
      progression, and 1 (14%) could not be assessed because of inability to tolerate
      infusions. One patient received surgery, cetuximab, and radiation, and remains
      disease-free after 4 years. LIMITATIONS: Lack of randomization, blinding, a true
      control arm, or standardization of treatment protocols are limitations.
      CONCLUSIONS: Patients with very HCSCC may have improved outcomes with surgery and
      adjuvant cetuximab.

PMID- 23871720
TI  - Cathelicidin, kallikrein 5, and serine protease activity is inhibited during
      treatment of rosacea with azelaic acid 15% gel.
AB  - BACKGROUND: Excess cathelicidin and kallikrein 5 (KLK5) have been hypothesized to
      play a role in the pathophysiology of rosacea. OBJECTIVE: We sought to evaluate
      the effects of azelaic acid (AzA) on these elements of the innate immune system.
      METHODS: Gene expression and protease activity were measured in laboratory models
      and patients with rosacea during a 16-week multicenter, prospective, open-label
      study of 15% AzA gel. RESULTS: AzA directly inhibited KLK5 in cultured
      keratinocytes and gene expression of KLK5, Toll-like receptor-2, and cathelicidin
      in mouse skin. Patients with rosacea showed reduction in cathelicidin and KLK5
      messenger RNA after treatment with AzA gel. Subjects without rosacea had lower
      serine protease activity (SPA) than patients with rosacea. Distinct subsets of
      patients with rosacea who had high and low baseline SPA were identified, and
      patients with high baseline exhibited a statistically significant reduction of
      SPA with 15% AzA gel treatment. LIMITATIONS: Study size was insufficient to
      predict clinical efficacy based on the innate immune response to AzA.
      CONCLUSIONS: These results show that cathelicidin and KLK5 decrease in
      association with AZA exposure. Our observations suggest a new mechanism of action
      for AzA and that SPA may be a useful biomarker for disease activity.

PMID- 23871721
TI  - Arterial pseudoaneurysm as a false positive for infection in bone scintigraphy
      and with labelled leukocytes in a patient with total hip prosthesis.

PMID- 23871722
TI  - XLID-causing mutations and associated genes challenged in light of data from
      large-scale human exome sequencing.
AB  - Because of the unbalanced sex ratio (1.3-1.4 to 1) observed in intellectual
      disability (ID) and the identification of large ID-affected families showing X
      linked segregation, much attention has been focused on the genetics of X-linked
      ID (XLID). Mutations causing monogenic XLID have now been reported in over 100
      genes, most of which are commonly included in XLID diagnostic gene panels.
      Nonetheless, the boundary between true mutations and rare non-disease-causing
      variants often remains elusive. The sequencing of a large number of control X
      chromosomes, required for avoiding false-positive results, was not systematically
      possible in the past. Such information is now available thanks to large-scale
      sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome
      Sequencing Project, which provides variation information on 10,563 X chromosomes
      from the general population. We used this NHLBI cohort to systematically reassess
      the implication of 106 genes proposed to be involved in monogenic forms of XLID.
      We particularly question the implication in XLID of ten of them (AGTR2, MAGT1,
      ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which
      truncating variants or previously published mutations are observed at a
      relatively high frequency within this cohort. We also highlight 15 other genes
      (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3,
      RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted.
      We propose that similar reassessment of reported mutations (and genes) with the
      use of data from large-scale human exome sequencing would be relevant for a wide
      range of other genetic diseases. 

PMID- 23871723
TI  - Imprinted chromatin around DIRAS3 regulates alternative splicing of GNG12-AS1, a
      long noncoding RNA.
AB  - Imprinted gene clusters are regulated by long noncoding RNAs (lncRNAs), CCCTC
      binding factor (CTCF)-mediated boundaries, and DNA methylation. DIRAS3 (also
      known as ARH1 or NOEY1) is an imprinted gene encoding a protein belonging to the
      RAS superfamily of GTPases and is located within an intron of a lncRNA called
      GNG12-AS1. In this study, we investigated whether GNG12-AS1 is imprinted and
      coregulated with DIRAS3. We report that GNG12-AS1 is coexpressed with DIRAS3 in
      several tissues and coordinately downregulated with DIRAS3 in breast cancers.
      GNG12-AS1 has several splice variants, all of which initiate from a single
      transcription start site. In placenta tissue and normal cell lines, GNG12-AS1 is
      biallelically expressed but some isoforms are allele-specifically spliced.
      Cohesin plays a role in allele-specific splicing of GNG12-AS1. In breast cancer
      cell lines with loss of DIRAS3 imprinting, DIRAS3 and GNG12-AS1 are silenced in
      cis and the remaining GNG12-AS1 transcripts are predominantly monoallelic. The
      GNG12-AS1 locus, which includes DIRAS3, provides an example of imprinted
      cotranscriptional splicing and a potential model system for studying the long
      range effects of CTCF-cohesin binding on splicing and transcriptional
      interference. 

PMID- 23871724
TI  - PK/PD models in antibacterial development.
AB  - There is an urgent need for novel antibiotics to treat life-threatening
      infections caused by bacterial 'superbugs'. Validated in vitro
      pharmacokinetic/pharmacodynamic (PK/PD) and animal infection models have been
      employed to identify the most predictive PK/PD indices and serve as key tools in
      the antibiotic development process. The results obtained can be utilized for
      optimizing study designs in order to minimize the cost and duration of clinical
      trials. This review outlines the key in vitro PK/PD and animal infection models
      which have been extensively used in antibiotic discovery and development. These
      models have shown great potential in accelerating drug development programs and
      will continue to make significant contributions to antibiotic development. 

PMID- 23871725
TI  - Olfactory bulbectomy induces neuronal rearrangement in the entorhinal cortex in
      the rat.
AB  - In humans, depression has been associated with disturbances in olfactory
      circuitry. Symptoms of depression can be mimicked in animals after olfactory
      bulbectomy (OBX). Animal models of depression-like behavior produce similar
      neuronal rearrangements in various brain regions as seen in patients affected by
      depression. We have recently observed that OBX produces neuronal hypotrophy in
      the piriform cortex (PirC) and CA1 hippocampus as well as decreased adult cell
      proliferation in the dentate gyrus (DG) of hippocampus. Thus we further evaluated
      the effects of OBX in neuronal arborization and spine density in brain regions
      involved in the control of circadian circle, emotion and memory processing such
      as the prefrontal cortex (PFC), nucleus accumbens (NAcc), infralimbic cortex
      (ILC), orbitolateral cortex (OLC) and entorhinal cortex (EC). Our present results
      show that along with severe behavioral deficits observed in these animals, OBX
      considerably decreased dendritic branching and the total dendritic length in the
      EC, a major interface of the hippocampus and neocortical regions. The remaining
      cortices and NAcc were not affected by OBX. Thus, we propose that the lack of
      input from the olfactory bulbs resulted in serial neuronal rearrangements in the
      PirC, EC, and hippocampus leading, at least partially, to behavioral deficits in
      emotion and memory processes. 

PMID- 23871726
TI  - Body mass index and stroke: overweight and obesity less often associated with
      stroke recurrence.
AB  - BACKGROUND: Although obesity is associated with excess mortality and morbidity,
      mortality is lower in obese than in normal weight stroke patients (the obesity
      paradox). Studies now indicate that obesity is not associated with increased risk
      of recurrent stroke in the years after first stroke. We studied the association
      between body mass index (BMI) and stroke patient's risk of having a history of
      previous stroke (recurrent stroke). METHODS: A registry designed to collect data
      on all hospitalized stroke patients in Denmark 2000-2010 includes 61,872 acute
      stroke patients with information on BMI in 38,506. Data include age, sex, civil
      status, stroke severity (Scandinavian Stroke Scale), computed tomography, and
      cardiovascular risk factors. There were 28,382 patients with complete covariate
      information. We used multiple logistic regression models on this data set to
      compare the risk of stroke being recurrent in the 4 BMI groups: underweight
      (BMI<18.5), normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), and obese
      (BMI>=30.0). RESULTS: Of the patients with complete covariate information, 22,811
      (80.1%) had first-ever stroke; in 5571 patients (19.6%), stroke was recurrent.
      Multiple logistic regression analysis adjusting for age, stroke severity, sex,
      BMI, civil status, and cardiovascular risk factors showed that being obese and
      overweight in comparison with normal weight was associated with a significantly
      lower risk of stroke being recurrent (obese: odds ratio [OR]=.90, confidence
      interval [CI] .82-.98; overweight: OR=.89, CI .83-.96). Being underweight was
      associated with a significantly higher risk of stroke being recurrent (OR=1.23;
      CI 1.06-1.43). CONCLUSIONS: The obesity paradox in stroke can be extended to
      include also stroke recurrence. Obese and overweight stroke patients had
      experienced less previous strokes than normal weight stroke patients.

PMID- 23871727
TI  - Apolipoprotein E genotypes associated with Alzheimer disease and concomitant
      stroke.
AB  - BACKGROUND: The E4 allele of the apolipoprotein E (APOE) gene is a well
      characterized genetic risk factor for Alzheimer disease (AD). The association
      between stroke and a higher risk for AD has also been reported. Our study sought
      to determine the relationship between the APOE gene and AD and the comorbid risk
      of stroke. METHODS: The subjects of this study consisted of 48 patients with AD
      and 48 members of a control group. All subjects were genotyped for APOE. RESULTS:
      The results clearly show a significant increased risk of AD in carriers of the
      APOE epsilon3/epsilon4 genotype (P = .003, odds ratio [OR] = 4.1) or epsilon4
      allele (P = .001, OR = 4.2). The risk for stroke in AD patients was also
      increased for carriers of the APOE epsilon3/epsilon4 genotype (P = .02, OR = 9.0)
      and for carriers of the APOE epsilon4 allele (P = .004, OR = 5.5). CONCLUSIONS:
      The present study is the first to establish a relationship between APOE epsilon4
      and concomitant AD and stroke in the Tunisian population.

PMID- 23871728
TI  - Evaluating middle cerebral artery atherosclerotic lesions in acute ischemic
      stroke using magnetic resonance T1-weighted 3-dimensional vessel wall imaging.
AB  - BACKGROUND: Atherosclerotic lesions in intracranial arteries are a leading cause
      of ischemic stroke. Magnetic resonance angiography (MRA) is often used to assess
      atherosclerotic changes by detecting luminal narrowing, whereas it cannot
      directly visualize atherosclerotic lesions. Here, we used a 3-dimensional vessel
      wall imaging (3D-VWI) technique to evaluate intracranial arterial wall changes in
      acute stroke. METHODS: Eighteen consecutive patients with acute noncardioembolic
      stroke in the middle cerebral artery (MCA) territory who were prospectively
      examined with a 1.5-T magnetic resonance scanner were studied. T1-weighted (T1-W)
      3D-VWI was obtained using a flow-sensitized 3D fast-spin echo technique. Wall
      thickening of MCA that suggests atherosclerotic plaques was visually evaluated
      and the contrast ratio (CR) of signal intensity of the lesions to that of the
      corpus callosum was calculated and compared with stenotic changes by MRA.
      RESULTS: Wall thickenings of the MCA ipsilateral and contralateral to the lesion
      were observed in almost all patients on 3D-VWI (94.4% and 94.4%, respectively),
      whereas MRA showed stenotic changes of 50% only in 1 patient (5.9%; P < .001).
      The CR of the thickened wall in the ipsilateral MCA was significantly higher than
      that in the contralateral MCA (median, .53 and .45, respectively; P = .028),
      suggesting of unstable plaques consisting of hemorrhage or lipid. CONCLUSIONS:
      The T1-W 3D-VWI can provide direct visualization of atherosclerotic lesions of
      the intracranial arteries in stroke patients, and it can detect signal change
      suggestive of unstable plaque.

PMID- 23871730
TI  - Ophthalmic complications of microscopic polyangiitis: an often overlooked disease
      entity.

PMID- 23871729
TI  - The effect of Ginkgo biloba on functional outcome of patients with acute ischemic
      stroke: a double-blind, placebo-controlled, randomized clinical trial.
AB  - BACKGROUND: Acute ischemic stroke is a major cerebrovascular disease with
      potential morbidity and mortality. Despite the availability of thrombolytic
      therapy in some centers, risk factor modification and rehabilitation therapy are
      the mainstays of stroke management. There is supporting evidence that Ginkgo
      biloba may afford neuroprotection and improve the outcomes of patients with acute
      ischemic stroke. METHODS: In a double-blind, placebo-controlled, randomized
      controlled trial, we assessed the efficacy of G biloba on functional outcome in
      patients with acute stroke. The National Institutes of Heath Stroke Scale (NIHSS)
      was used to measure functional outcome. A total of 102 patients with acute
      ischemic stroke were studied. All patients received either G biloba or placebo
      tablets for 4 months. This trial was registered to the Iranian Registry of
      Clinical Trials (www.irct.ir; trial IRCT138804212150N1). RESULTS: There were 52
      patients who received G biloba and 50 patients who were in the placebo group.
      Age, sex distribution, previous medical condition, and laboratory data did not
      have any significant difference between the 2 groups (P>.05). The mean difference
      of 4-month follow-up NIHSS scores and NIHSS scores at admission was 4.7+/-2.7 and
      4.1+/-3.0 in the G biloba and placebo groups, respectively (P>.05). The primary
      outcome-a 50% reduction in the 4-month follow-up NIHSS score compared to the
      baseline NIHSS score-was reached in 17 patients (58.6%) and 5 patients (18.5%) in
      the G biloba and placebo groups, respectively (P<.05). The risk ratio and number
      needed to treat were 3.16 (confidence interval 1.35-7.39) and 2.50 (confidence
      interval 1.58-5.90), respectively. In addition, multivariate regression adjusted
      for age and sex revealed a significant NIHSS decline in the G biloba group
      compared to the placebo group (P<.05). CONCLUSIONS: Our data suggest that G
      biloba may have protective effects in ischemic stroke. Therefore, the
      administration of G biloba is recommended after acute ischemic stroke.

PMID- 23871732
TI  - Genetic variations in toll-like receptor 4 in Mexican-Mestizo patients with intra
      abdominal infection and/or pneumonia.
AB  - Sepsis is a leading cause of death around the world, and 73-83% of all sepsis
      cases requiring attention in intensive care units are linked to intra-abdominal
      infection (IAI) or pneumonia. The activation of innate immunity is central to the
      manifestation of sepsis, and toll-like receptor (TLR) 4 plays an important role
      in this activation process. The 299G and 399I alleles of TLR4 have been linked
      with an increased risk of Gram-negative bacteria (GNB) infections and septic
      shock in some populations. This case-control study evaluated the prevalence of
      D299G/T399I polymorphisms in Mexican patients with IAI and/or pneumonia and in
      healthy controls. Genotyping revealed that 1 in 44 patients (2.3%; CI 95%: 0.05
      12.0%) and 4 in 126 controls (3.2%; CI 95%: 0.9-7.9%) were heterozygous for both
      the D299G and T399l polymorphisms (OR: 0.71, CI 95%: 0.01-7.44, p = NS),
      confirming the co-segregation of these alleles in this population. Furthermore,
      the patients with a GNB infection and severe sepsis were not carriers of the risk
      alleles. In summary, this report shows that the frequency of the D299G and T399I
      polymorphisms in Mexican-Mestizos is lower than anticipated in comparison with
      other ethnic groups, emphasizing the variable distribution of TLR4 polymorphisms
      among different populations. Consequently, this study was not able to detect
      associations between TLR4 polymorphisms and sepsis in this population.

PMID- 23871731
TI  - Cerebral hyperemia measured with near infrared spectroscopy during treatment of
      diabetic ketoacidosis in children.
AB  - OBJECTIVE: To use near infrared spectroscopy (NIRS) to evaluate the timing of
      onset and duration of cerebral hyperemia during diabetic ketoacidosis (DKA)
      treatment in children, and to investigate the relationship of cerebral hyperemia
      to intravenous fluid treatment. STUDY DESIGN: We randomized children aged 8-18
      years with DKA to either more rapid or slower intravenous fluid treatment (19
      total DKA episodes). NIRS was used to measure rSo2 during DKA treatment. NIRS
      monitoring began as soon as informed consent was obtained and continued until the
      patient was transferred out of the critical care unit. RESULTS: rSo2 values above
      the normal range (>80%) were detected in 17 of 19 DKA episodes (mean rSo2 during
      initial 8 hours of DKA treatment: 86% +/- 7%, range 65%-95%). Elevated rSo2
      values were detected as early as the second hour of DKA treatment and persisted
      for as long as 27 hours. Hourly mean rSo2 levels during treatment did not differ
      significantly by fluid treatment group. CONCLUSIONS: During DKA treatment,
      children have elevated rSo2 values consistent with cerebral hyperemia. Hyperemia
      occurs as early as the second hour of DKA treatment and may persist for >= 27
      hours. Cerebral rSo2 levels during treatment did not differ significantly in
      patients treated with slower versus more rapid intravenous rehydration.

PMID- 23871734
TI  - A methodology for optimal MSW management, with an application in the waste
      transportation of Attica Region, Greece.
AB  - The paper describes a software system capable of formulating alternative optimal
      Municipal Solid Wastes (MSWs) management plans, each of which meets a set of
      constraints that may reflect selected objections and/or wishes of local
      communities. The objective function to be minimized in each plan is the sum of
      the annualized capital investment and annual operating cost of all
      transportation, treatment and final disposal operations involved, taking into
      consideration the possible income from the sale of products and any other
      financial incentives or disincentives that may exist. For each plan formulated,
      the system generates several reports that define the plan, analyze its cost
      elements and yield an indicative profile of selected types of installations, as
      well as data files that facilitate the geographic representation of the optimal
      solution in maps through the use of GIS. A number of these reports compare the
      technical and economic data from all scenarios considered at the study area,
      municipality and installation level constituting in effect sensitivity analysis.
      The generation of alternative plans offers local authorities the opportunity of
      choice and the results of the sensitivity analysis allow them to choose wisely
      and with consensus. The paper presents also an application of this software
      system in the capital Region of Attica in Greece, for the purpose of developing
      an optimal waste transportation system in line with its approved waste management
      plan. The formulated plan was able to: (a) serve 113 Municipalities and
      Communities that generate nearly 2 milliont/y of comingled MSW with distinctly
      different waste collection patterns, (b) take into consideration several existing
      waste transfer stations (WTS) and optimize their use within the overall plan, (c)
      select the most appropriate sites among the potentially suitable (new and in use)
      ones, (d) generate the optimal profile of each WTS proposed, and (e) perform
      sensitivity analysis so as to define the impact of selected sets of constraints
      (limitations in the availability of sites and in the capacity of their
      installations) on the design and cost of the ensuing optimal waste transfer
      system. The results show that optimal planning offers significant economic
      savings to municipalities, while reducing at the same time the present levels of
      traffic, fuel consumptions and air emissions in the congested Athens basin. 

PMID- 23871733
TI  - B-cell epitope peptide vaccination targeting dimer interface of epidermal growth
      factor receptor (EGFR).
AB  - Epidermal growth factor receptor (EGFR) was the first receptor to be proposed as
      the target for cancer therapy, however, the anti-EGFR therapy showed a low
      response rate clinically. Dimerization plays a key role in the activation of
      EGFR, so targeting the conservative dimer interface probably improve the
      responses of anti-EGFR clinically. To evoke a high titers of antibodies (Abs)
      targeting the dimer interface of EGFR in patients, a chimeric peptide, comprising
      a linear B-cell epitope peptide from the highly conservative beta-hairpin loop of
      dimer interface of human EGFR (EGFR237-267) and a 'promiscuous' Th-cell epitope
      MVF from the measles virus fusion protein, was constructed. The construct was
      immunogenic and able to elicit high titers of peptide-specific Abs in both mice
      and rabbits, while both animals' EGFRs contain a sequence 100% homologous to
      EGFR237-267. The peptide-specific Abs could recognize and inhibit EGFR over
      expressing epithelial cancer cells, such as epidermoid carcinoma A431 and Lewis
      lung cancer (LLC), furthermore, the binding of the Abs to the native EGFR on the
      surface of cells was ligand-dependent, which meant that these Abs did target the
      dimer interface of EGFR as designed, because the exposure of the interface needs
      ligand binding. The chimeric peptide immunization was able to significantly
      inhibit the growth of subcutaneously transplanted LLC cells in C57BL6 mice.
      Therefore, the MVF-EGFR237-267 construct represents a promising candidate for
      active anti-EGFR immunotherapy and provides a novel targeting strategy for the
      anti-EGFR therapy.

PMID- 23871735
TI  - A novel lab-scale screen extruder for studying extrusion-spheronisation.
AB  - A novel apparatus, the laboratory roller screen extruder (termed the LRS), was
      developed to replicate key aspects of the geometry and shear strain rates
      generated near the screen of industrial screen extruders. The configuration of
      the LRS is reported alongside a commissioning study employing a cohesive 45 wt%
      water/microcrystalline cellulose paste. The key operating parameters which
      controlled the extrudate mass flowrate, force on the screen and roller torque
      were (i) the size of the gap between the top of the roller blade and the screen,
      and (ii) the roller rotational speed. The data suggest that the apparent shear
      rate, based on the blade-screen clearance, provides a quantitative criterion for
      scale-up. The amount of screen flex showed good agreement with a simple bending
      deformation model. Spheronisation of the extrudates gave pellets with a narrow
      size distribution and acceptable sphericity which would be acceptable for capsule
      filling. Optimisation of the pellet shape was not performed. The results indicate
      that the LRS can be used to assess formulations for industrial screen extrusion
      spheronisation.

PMID- 23871736
TI  - Oleodendrimers: a novel class of multicephalous heterolipids as chemical
      penetration enhancers for transdermal drug delivery.
AB  - This paper reports synthesis and evaluation of Janus type generation G-1 and G-2
      dendrimers. The dendrimers have been constructed by linking two building blocks,
      dendrons and oleic acid, through ester and amide bonds and were well
      characterized by Fourier-transform infrared (FT-IR), (1)H NMR, (13)C NMR and
      electrospray ionization mass spectrometry (ESI-MS). The dendrimers have been
      evaluated for in vitro cytotoxicity using sulforhodamine B assay (SRB assay) and
      in vivo skin irritation potential. The ester linked dendrimers did not exhibit
      any cytotoxicity even up to 80 MUg/ml while G-1 and G-2 generations dendrimers
      with amide linkage exhibited toxicity above 70 MUg/ml and 21 MUg/ml,
      respectively, none of the dendrimers showed any skin irritation. All the
      dendrimers, tested for their skin permeation enhancement potential using
      diclofenac sodium (DS) as a model drug at a concentration of 1% in gels, showed
      significant increase in steady-state flux (ERflux) of the drug as compared to
      control (without enhancer), and oleic acid. Amongst the dendrimers, the ester
      linked G-1 and G-2 dendrimers showed highest ERflux, 3.33 +/- 0.31 and 3.39 +/-
      0.21, respectively.

PMID- 23871737
TI  - Strategies for the design of orally bioavailable antileishmanial treatments.
AB  - Leishmaniasis is one of the six major tropical diseases targeted by the World
      Health Organization. The most serious, life-threatening form is visceral
      leishmaniasis (VL). No vaccine is yet available for human use and chemotherapy is
      the main mean of dealing with this disease. This review focuses on the
      development of drug delivery systems (DDS) for treatment of leishmaniasis. After
      an overview of the significance of leishmaniasis in 2013, current chemotherapy
      and its limitations are considered, leading to possible strategies to improve the
      treatment of VL: new drugs, combinations of existing drugs and DDS, particularly
      for oral administration. Nanostructured biomaterials such as lipid-based or
      polymeric nanoparticles have unique physicochemical properties, ultra-small and
      controllable size, large surface area to mass ratio and the possibility of
      surface modification which can be used to advantage for the oral administration
      of antileishmanial drugs. They can improve the rate of dissolution of poorly
      water-soluble drugs, increase intestinal residence time by bioadhesion and,
      especially when lipid additives are used, influence the route and efficiency of
      absorption. These recent advances in this very active field should lead to better
      management of this serious disease. 

PMID- 23871738
TI  - A novel strategy to design sustained-release poorly water-soluble drug mesoporous
      silica microparticles based on supercritical fluid technique.
AB  - BACKGROUND: The organic solvent solution immersion method was often used to
      achieve the loading of the drugs into mesoporous silica, but the drugs that have
      loaded into the pores of the mesoporous silica would inevitable migrate from the
      inside to the external surface or near the outside surface during the process of
      drying. Hence, it often leads to the pores of mesoporous materials not be fully
      utilized, and results in a low drug loading efficiency and a fast releasing rate.
      OBJECTIVE: The purpose of this study was to develop a novel drug loading strategy
      to avoid soluble component migration during the process of drying, then, to
      prepare poorly water-soluble drug mesoporous silica microparticles with higher
      drug loading efficiency and longer sustained-release time. METHOD: Ibuprofen was
      used as model drug. The microparticles were prepared by a novel method based on
      mesoporous silica and supercritical fluid (SCF) technique. The drug-loaded
      mesoporous silica microparticles prepared by SCF technique were analyzed by
      thermogravimetric analysis (TGA), N2 adsorption/desorption, scanning electron
      microscopy (SEM), powder X-ray diffraction (XRD) and differential scanning
      calorimetry (DSC). In vitro releasing study was used to evaluate the sustained
      release effect of the drug-loaded microparticles. RESULTS: By virtue of the high
      diffusibility and the high dissolving capacity of the supercritical carbon
      dioxide (SCF-CO2), the poorly water-soluble drugs, ibuprofen, entered the pores
      of the mesoporous silica. The amount and the depth of ibuprofen entered the pores
      of the mesoporous silica by SCF technique were both larger than those by the
      solution immersion method. It was found that ibuprofen loaded into the mesoporous
      silica by SCF technique was amorphous and the largest amount of the ibuprofen
      loaded into the mesoporous silica by SCF technique could reach 386 mg/g (w/w,
      ibuprofen/SiO2), it was more than that by the solution immersion method. In vitro
      releasing study showed that the sustained-release effect of ibuprofen in the
      samples prepared by SCF technique was 50% in 15 min and 90% in 60 min. It was
      longer than that prepared by the solution immersion method. CONCLUSION: Present
      study showed that sustained-release poorly water-soluble drug mesoporous silica
      microparticle based on SCF technique has twofold advantages. One is the larger
      drug loading amount in internal pores of the mesoporous silica, the other is the
      longer drug releasing time.

PMID- 23871739
TI  - Nano-transfersomes as a novel carrier for transdermal delivery.
AB  - The aim of this study was to design and optimize a nano-transfersomes of
      Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3(3) factorial design (Box
      Behnken) was used to derive a polynomial equation (second order) to construct 2-D
      (contour) and 3-D (Response Surface) plots for prediction of responses. The ratio
      of lipid to surfactant (X1), weight of lipid to surfactant (X2) and sonication
      time (X3) (independent variables) and dependent variables [entrapment efficiency
      of DDEA (Y1), entrapment efficiency of CRM (Y2), effect on particle size (Y3),
      flux of DDEA (Y4), and flux of CRM (Y5)] were studied. The 2-D and 3-D plots were
      drawn and a statistical validity of the polynomials was established to find the
      compositions of optimized formulation. The design established the role of the
      derived polynomial equation, 2-D and 3-D plots in predicting the values of
      dependent variables for the preparation and optimization of nano-transfersomes
      for transdermal drug release.

PMID- 23871740
TI  - New silica nanostructure for the improved delivery of topical antibiotics used in
      the treatment of staphylococcal cutaneous infections.
AB  - In this paper, we report the synthesis, characterization (FT-IR, XRD, BET, HR
      TEM) and bioevaluation of a novel gamma-aminobutiric acid/silica (noted GABA-SiO2
      or gamma-SiO2) hybrid nanostructure, for the improved release of topical
      antibiotics, used in the treatment of Staphylococcus aureus infections. GABA-SiO2
      showed IR bands which were assigned to Si-O-Si (stretch mode). The XRD pattern
      showed a broad peak in the range of 18-30 degrees  (2theta), indicating an
      amorphous structure. Based on the BET analysis, estimations about surface area
      (438.14 m2/g) and pore diameters (4.76 nm) were done. TEM observation reveals
      that the prepared structure presented homogeneity and an average size of
      particles not exceeding 10nm. The prepared nanostructure has significantly
      improved the anti-staphylococcal activity of bacitracin and kanamycin sulfate, as
      demonstrated by the drastic decrease of the minimal inhibitory concentration of
      the respective antibiotics loaded in the GABA-SiO2 nanostructure. These results,
      correlated with the high biocompatibility of this porous structure, are
      highlighting the possibility of using this carrier for the local delivery of the
      antimicrobial substances in lower active doses, thus reducing their cytotoxicity
      and side-effects.

PMID- 23871741
TI  - Long term alterations in synaptic physiology, expression of beta2 nicotinic
      receptors and ERK1/2 signaling in the hippocampus of rats with prenatal nicotine
      exposure.
AB  - Smoking during pregnancy is associated with long lasting, hippocampus dependent,
      cognitive deficits in children. The current study was performed to investigate
      the effect of prenatal nicotine exposure on excitatory synaptic physiology and
      cellular signaling in the hippocampus using a rodent model. Excitatory synaptic
      physiology was analyzed using electrophysiological methods to detect changes in
      synaptic plasticity, excitatory synaptic transmission and synaptic currents
      mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
      (AMPARs) in the hippocampus. Additionally, western blot experiments were
      performed to quantify alterations in protein expression levels in the
      hippocampus. Prenatal nicotine exposure resulted in a decrease in long term
      potentiation (LTP) and an increase in long term depression (LTD). Basal synaptic
      transmission was also reduced with a concomitant decline in AMPAR mediated
      synaptic currents at the cellular and single channel levels. Presynaptic pool of
      vesicles docked close to release sites were also diminished in nicotine exposed
      rats. Moreover, reduced levels of beta2 subunit containing nicotinic receptors
      and extracellular signal regulated kinase1/2 (ERK1/2) were observed in nicotine
      exposed rats. These results suggest that long lasting alterations in excitatory
      synaptic physiology, AMPAR synaptic currents and ERK1/2 signaling may serve as
      the molecular mechanisms for cognitive deficits associated with prenatal nicotine
      exposure. 

PMID- 23871742
TI  - Role of adult neurogenesis in hippocampus-dependent memory, contextual fear
      extinction and remote contextual memory: new insights from ERK5 MAP kinase.
AB  - Adult neurogenesis occurs in two discrete regions of the adult mammalian brain,
      the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone
      (SVZ) along the lateral ventricles. Signaling mechanisms regulating adult
      neurogenesis in the SGZ are currently an active area of investigation. Adult-born
      neurons in the DG functionally integrate into the hippocampal circuitry and form
      functional synapses, suggesting a role for these neurons in hippocampus-dependent
      memory formation. Although results from earlier behavioral studies addressing
      this issue were inconsistent, recent advances in conditional gene targeting
      technology, viral injection and optogenetic approaches have provided convincing
      evidence supporting a role for adult-born neurons in the more challenging forms
      of hippocampus-dependent learning and memory. Here, we briefly summarize these
      recent studies with a focus on extra signal-regulated kinase (ERK) 5, a MAP
      kinase whose expression in the adult brain is restricted to the neurogenic
      regions including the SGZ and SVZ. We review evidence identifying ERK5 as a novel
      endogenous signaling pathway that regulates the pro-neural transcription factor
      Neurogenin 2, is activated by neurotrophins and is critical for adult
      neurogenesis. We discuss studies demonstrating that specific deletion of ERK5 in
      the adult neurogenic regions impairs several forms of hippocampus-dependent
      memory formation in mice. These include contextual fear memory extinction, the
      establishment and maintenance of remote contextual fear memory, and several other
      challenging forms of hippocampus-dependent memory formation including 48h memory
      for novel object recognition, contextual fear memory established by a weak foot
      shock, pattern separation, and reversal of spatial learning and memory. We also
      briefly discuss current evidence that increasing adult neurogenesis, by small
      molecules or genetic manipulation, improves memory formation and long-term
      memory. 

PMID- 23871743
TI  - Central cholinergic involvement in sequential behavior: impairments of
      performance by atropine in a serial multiple choice task for rats.
AB  - Two experiments examined whether muscarinic cholinergic systems play a role in
      rats' ability to perform well-learned highly-structured serial response patterns,
      particularly focusing on rats' performance on pattern elements learned by
      encoding rules versus by acquisition of stimulus-response (S-R) associations.
      Rats performed serial patterns of responses in a serial multiple choice task in
      an 8-lever circular array for hypothalamic brain-stimulation reward. Two
      experiments examined the effects of atropine, a centrally-acting muscarinic
      cholinergic receptor antagonist, on rats' ability to perform pattern elements
      where responses were controlled by rules versus elements, such as rule
      inconsistent "violation elements" and elements following "phrasing cues," where
      responses were controlled by associative cues. In Experiment 1, 3-element chunks
      of both patterns were signaled by pauses that served as phrasing cues before
      chunk-boundary elements, but one pattern also included a violation element that
      was inconsistent with pattern structure. Once rats reached a high criterion of
      performance, the drug challenge was intraperitoneal injection of a single dose of
      50 mg/kg atropine sulfate. Atropine impaired performance on elements learned by S
      R learning, namely, chunk-boundary elements and the violation element, but had no
      effect on performance of rule-based within-chunk elements. In Experiment 2,
      patterns were phrased and unphrased perfect patterns (i.e., without violation
      elements). To control for peripheral effects of atropine, rats were treated with
      a series of doses of either centrally-acting atropine or peripherally-acting
      atropine methyl nitrate (AMN), which does not cross the blood-brain barrier. Once
      rats reached a high criterion, the drug challenges were on alternate days in the
      order 50, 25, and 100 mg/kg of either atropine sulfate or AMN. Atropine, but not
      AMN, impaired performance in the phrased perfect pattern for pattern elements
      where S-R associations were important for performance, namely, chunk-boundary
      elements. However, in the structurally more ambiguous unphrased perfect pattern
      where rats had fewer cues and presumably relied more on S-R associations
      throughout, atropine impaired performance on all pattern elements. Thus, intact
      muscarinic cholinergic systems were shown to be necessary for discriminative
      control previously established by S-R learning, but were not necessary for rule
      based serial pattern performance.

PMID- 23871746
TI  - Covariate-adjusted confidence interval for the intraclass correlation
      coefficient.
AB  - A crucial step in designing a new study is to estimate the required sample size.
      For a design involving cluster sampling, the appropriate sample size depends on
      the so-called design effect, which is a function of the average cluster size and
      the intracluster correlation coefficient (ICC). It is well-known that under the
      framework of hierarchical and generalized linear models, a reduction in residual
      error may be achieved by including risk factors as covariates. In this paper we
      show that the covariate design, indicating whether the covariates are measured at
      the cluster level or at the within-cluster subject level affects the estimation
      of the ICC, and hence the design effect. Therefore, the distinction between these
      two types of covariates should be made at the design stage. In this paper we use
      the nested-bootstrap method to assess the accuracy of the estimated ICC for
      continuous and binary response variables under different covariate structures.
      The codes of two SAS macros are made available by the authors for interested
      readers to facilitate the construction of confidence intervals for the ICC.
      Moreover, using Monte Carlo simulations we evaluate the relative efficiency of
      the estimators and evaluate the accuracy of the coverage probabilities of a 95%
      confidence interval on the population ICC. The methodology is illustrated using a
      published data set of blood pressure measurements taken on family members. 

PMID- 23871745
TI  - Non-spatial pre-training in the water maze as a clinically relevant model for
      evaluating learning and memory in experimental TBI.
AB  - Explicit and implicit learning and memory networks exist where each network can
      facilitate or inhibit cognition. Clinical evidence suggests that implicit
      networks are relatively preserved after traumatic brain injury (TBI). Non-spatial
      pre-training (NSPT) in the Morris Water Maze (MWM) provides the necessary
      behavioral components to complete the task, while limiting the formation of
      spatial maps. Our study utilized NSPT in the MWM to assess implicit and explicit
      learning and memory system deficits in the controlled cortical impact (CCI) model
      of TBI. 76 adult male Sprague-Dawley rats were divided: CCI vs. sham surgery,
      NSPT vs. No-NSPT, and cued vs. non-cued groups. NSPT occurred for 4d prior to
      surgery (dynamic hidden platform location, extra-maze cues covered, static pool
      entry point). Acquisition (d14-18), Probe/Visible Platform (d19), and Reversal
      (d20-21) trials were conducted with or without extra-maze cues. Novel time
      allocation and search strategy selection metrics were utilized. Results indicated
      implicit and explicit learning/memory networks are distinguishable in the MWM. In
      the cued condition, NSPT reduced thigmotaxis, improved place learning, and
      largely eliminated the apparent injury-induced deficits typically observed
      between untrained CCI and sham rats. However, among NSPT groups, incorporation of
      cues into search strategy selection for CCI rats was relatively impaired compared
      to shams. Non-cued condition performance showed sham/NSPT and CCI/NSPT rats
      perform similarly, suggesting implicit memory networks are largely intact 2weeks
      after CCI. Place learning differences between CCI/NSPT and sham/NSPT rats more
      accurately reflect spatial deficits in our CCI model compared to untrained
      controls. These data suggest NSPT as a clinically relevant construct for
      evaluating potential neurorestorative and neuroprotective therapies. These
      findings also support development of non-spatial cognitive training paradigms for
      evaluating rehabilitation relevant combination therapies. 

PMID- 23871747
TI  - Association between metabolic syndrome and osteoporosis: a meta-analysis.
AB  - Metabolic syndrome (MetS) consists of several independent clinically recognisable
      features that have their own independent effects on bone metabolism, and even a
      single disease could have apparently contradictory effects on bone metabolism.
      This meta-analysis aimed to detect a relationship between MetS and osteoporosis.
      The PubMed, Embase, and Cochrane library databases were searched for relevant
      studies published before April 1, 2013. On June 22, 2013, the databases were
      searched again for additional studies. Studies clearly reporting a comparison of
      bone mineral density (BMD) in subjects with or without MetS were selected for our
      analysis. From these results, we analysed the crude BMD and the BMD adjusted for
      all covariates (age, weight, height, alcohol intake, cigarette smoking and
      exercise). Weighted mean differences were calculated using a random-effects
      model. Nine studies were included in this meta-analysis. No significant
      differences were found when analysing the crude lumbar spine BMD and the femoral
      neck BMD. However, the MetS (-) group showed a significantly higher BMD when all
      covariates were adjusted for femoral neck BMD (0.02, p=0.0002) and lumbar spine
      BMD (0.01, p=0.007). Subgroup analysis suggested a negative effect of MetS on BMD
      in men but not in women. These findings suggest that MetS is a risk factor for
      developing osteoporosis in men. 

PMID- 23871744
TI  - Learning to learn - intrinsic plasticity as a metaplasticity mechanism for memory
      formation.
AB  - "Use it or lose it" is a popular adage often associated with use-dependent
      enhancement of cognitive abilities. Much research has focused on understanding
      exactly how the brain changes as a function of experience. Such experience
      dependent plasticity involves both structural and functional alterations that
      contribute to adaptive behaviors, such as learning and memory, as well as
      maladaptive behaviors, including anxiety disorders, phobias, and posttraumatic
      stress disorder. With the advancing age of our population, understanding how use
      dependent plasticity changes across the lifespan may also help to promote healthy
      brain aging. A common misconception is that such experience-dependent plasticity
      (e.g., associative learning) is synonymous with synaptic plasticity. Other forms
      of plasticity also play a critical role in shaping adaptive changes within the
      nervous system, including intrinsic plasticity - a change in the intrinsic
      excitability of a neuron. Intrinsic plasticity can result from a change in the
      number, distribution or activity of various ion channels located throughout the
      neuron. Here, we review evidence that intrinsic plasticity is an important and
      evolutionarily conserved neural correlate of learning. Intrinsic plasticity acts
      as a metaplasticity mechanism by lowering the threshold for synaptic changes.
      Thus, learning-related intrinsic changes can facilitate future synaptic
      plasticity and learning. Such intrinsic changes can impact the allocation of a
      memory trace within a brain structure, and when compromised, can contribute to
      cognitive decline during the aging process. This unique role of intrinsic
      excitability can provide insight into how memories are formed and, more
      interestingly, how neurons that participate in a memory trace are selected. Most
      importantly, modulation of intrinsic excitability can allow for regulation of
      learning ability - this can prevent or provide treatment for cognitive decline
      not only in patients with clinical disorders but also in the aging population. 

PMID- 23871748
TI  - A quantitative framework for the 3D characterization of the osteocyte lacunar
      system.
AB  - Assessing the role of osteocyte lacunae and the ways in which they communicate
      with one another is important for determining the function and viability of bone
      tissue. Osteocytes are able to play a significant role in bone development and
      remodeling because they can receive nourishment from, interact with, and
      communicate with other cells. In this sense the immediate environment of an
      osteocyte is crucial for understanding its function. Modern imaging techniques,
      ranging from synchrotron radiation-based computed tomography (SR CT) to confocal
      laser scanning microscopy, produce large volumes of high-quality imaging data of
      bone tissue on the micrometer scale in rapidly shortening times. These images
      often contain tens of thousands of osteocytes and their lacunae, void spaces
      which enclose the osteocytes. While theoretically possible, quantitative analysis
      of the osteocyte lacunar system is too time consuming to be practical without
      highly automated tools. Moreover, quantitative morphometry of the osteocyte
      lacunar system necessitates clearly defined, robust, and three-dimensional (3D)
      measures. Here, we introduce a framework for the quantitative characterization of
      millions of osteocyte lacunae and their spatial relationships in 3D. The metrics
      complement and expand previous works looking at shape and number density while
      providing novel measures for quantifying spatial distribution and alignment. We
      developed model, in silico systems to visualize and validate the metrics and
      provide a concrete example of the attribute being classified with each metric. We
      then illustrate the applicability to biological samples in a first study
      comparing two strains of mice and the effect of growth hormone. We found
      significant differences in shape and distribution between strains for alignment.
      The proposed quantitative framework can be used in future studies examining
      differences and treatment effects in bone microstructure at the cell scale.
      Furthermore, the proposed strategy for quantitative bone cell morphometry will
      allow investigating structure-function relationships in bone tissue, for example
      by linking cellular morphometry to bone remodeling. 

PMID- 23871749
TI  - Atypical fracture of the tibial diaphysis associated with bisphosphonate therapy:
      a case report.
AB  - Atypical subtrochanteric femoral shaft fractures (AFFs) have recently emerged as
      a potential long-term complication of bisphosphonate therapy. In 2010, the
      American Society for Bone and Mineral Research (ASBMR) Task Force published a
      definition for AFF consisting of 5 major and 7 minor features. Little attention
      has so far been paid to the possibility that bisphosphonate-associated atypical
      fractures may also involve the diaphysis of other long bones. We report here the
      case of a patient on long-term bisphosphonate therapy who presented a diaphyseal
      tibial insufficiency fracture fulfilling all the major criteria (except for the
      location), and a number of the minor criteria of an atypical fracture. Our case
      report suggests the need for greater awareness of the possibility of atypical
      fractures at other sites, particularly in weight-bearing long bones other than
      the femur, and suggests that long-term bisphosphonate therapy may also contribute
      to the occurrence of these atypical fractures. 

PMID- 23871751
TI  - Single nucleotide deletion of cqm1 gene results in the development of resistance
      to Bacillus sphaericus in Culex quinquefasciatus.
AB  - The entomopathogen Bacillus sphaericus is one of the most effective biolarvicides
      used to control the Culex species of mosquito. The appearance of resistance in
      mosquitoes to this bacterium, however, remains a threat to its continuous use in
      integrated mosquito control programs. Previous work showed that the resistance to
      B. sphaericus in Culex colonies was associated with the absence of the 60-kDa
      binary toxin receptor (Cpm1/Cqm1), an alpha-glucosidase present in the larval
      midgut microvilli. In this work, we studied the molecular basis of the resistance
      developed by Culex quinquefasciatus to B. sphaericus C3-41. The cqm1 genes were
      cloned from susceptible (CqSL) and resistant (CqRL/C3-41) colonies, respectively.
      The sequence of the cDNA and genomic DNA derived from CqRL/C3-41 colony differed
      from that of CqSL one by a one-nucleotide deletion which resulted in a premature
      stop codon, leading to production of a truncated protein. Recombinant Cqm1S from
      the CqSL colony expressed in Escherichia coli specifically bound to the Bin toxin
      and had alpha-glucosidase activity, whereas the Cqm1R from the CqRL/C3-41 colony,
      with a deletion of three quarters of the receptor's C-terminal lost its alpha
      glucosidase activity and could not bind to the binary toxin. Immunoblotting
      experiments showed that Cqm1 was undetectable in CqRL/C3-41 larvae, although the
      gene was correctly transcribed. Thus, the cqm1R represents a new allele in C.
      quinquefasciatus that confers resistance to B. sphaericus. 

PMID- 23871750
TI  - Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor
      systems.
AB  - Cigarette smoking is the leading preventable cause of death in the Western world,
      with a considerably higher prevalence observed in schizophrenia compared to the
      general population. Despite the negative health consequences of smoking heavily,
      it has been proposed that individuals with schizophrenia may maintain smoking
      behaviors to remediate symptoms associated with the disorder. Neurocognitive
      deficits are a core feature of schizophrenia and are present in approximately 80%
      of patients. Further, these deficits constitute an endophenotype of
      schizophrenia, as they are stable across disease phases, and are heritable. The
      neurocognitive deficits that are present in schizophrenia are especially
      debilitating, since they are associated with poor clinical and functional
      outcomes and community integration. Interestingly, these deficits may also
      constitute a vulnerability factor towards the initiation and maintenance of
      tobacco use. Contributing to the potential shared vulnerability between
      schizophrenia and tobacco dependence is a dysregulation of the nicotinic
      acetylcholine receptor (nAChR) system. Pre-clinical evidence has shown that
      nicotine affects several neurotransmitter systems, including dopamine (DA),
      glutamate, and gamma-aminobutyric acid (GABA), and certain neuropsychological
      deficits associated with these neurotransmitters (reaction time, spatial working
      memory, sustained attention, and sensory gating) are improved after nicotine
      administration in patients with schizophrenia. These positive effects on
      neurocognition appear to be more pronounced in smokers with schizophrenia, and
      may be an important mechanism that explains the co-morbidity of schizophrenia and
      tobacco dependence. 

PMID- 23871752
TI  - Cathepsin A protein from the accessory sex gland of the Chinese mitten crab
      (Eriocheir sinensis) plays a key role in spermatophore digestion.
AB  - Accessory sex gland (ASG) secretory proteins of the Chinese mitten crab
      (Eriocheir sinensis) can effectively digest the spermatophore wall. In order to
      identify which proteins participate in spermatophore wall digestion, a 50-kDa
      protein secreted from the ASG was purified to homogeneity by a series of
      isolation steps, including ammonium sulfate fractionation, Sephadex G-25 S gel
      filtration, ion exchange chromatography on a DEAE-Sephacel column and Sephacryl S
      200 gel-filtration. The purified protein was effective in spermatophore wall
      rupture, and the subsequent HPLC-ESI-MS/MS shotgun analysis showed the digestive
      protein to be cathepsin A (cathA). This finding was also confirmed by Western
      blot analysis and a cathA inhibitor digestion experiment. ELISA analysis showed
      that cathA enzymatic activity from ASG secretions increased during its
      purification process. Furthermore, enzymatic activity was significantly higher in
      the mating period of E. sinensis parallel to the latest developmental stage of
      the gland. Moreover, analysis from a cathA inhibitor that inhibits spermatophore
      wall digestion showed that cathA is the main enzyme involved. Hence, we first
      report the characterization of cathA from the ASG, which might play a key role in
      digesting the spermatophore wall of E. sinensis. 

PMID- 23871753
TI  - Does EU legislation allow the use of the Benchmark Dose (BMD) approach for risk
      assessment?
AB  - Hazard characterisation is largely based on an approach of (statistically)
      comparing dose groups with the controls in order to derive points of departure
      such as no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse
      effect levels (LOAELs). This approach suggests the absence of any relevant effect
      at the NOAEL. The NOAEL approach has been debated for decades. A recent
      Scientific Opinion by the European Food Safety Authority (EFSA) concluded that
      the Benchmark Dose (BMD) approach should be preferred over the NOAEL approach for
      deriving human (health-based) limit or guidance values. Nonetheless, the BMD
      approach is used infrequently within European regulatory frameworks. The reason
      for this may lie in legislation or guidelines requiring the use of the NOAEL
      approach. In this context, various EU regulatory frameworks were examined on such
      demands. Interestingly, no single legislation was identified containing statutory
      requirements in conflict with the use of the BMD approach. 

PMID- 23871754
TI  - Ancestor of the new archetypal biology: Goethe's dynamic typology as a model for
      contemporary evolutionary developmental biology.
AB  - As understood historically, typological thinking has no place in evolutionary
      biology since its conceptual framework is viewed as incompatible with population
      thinking. In this article, I propose that what I describe as dynamic typological
      thinking has been confused with, and has been overshadowed by, a static form of
      typological thinking. This conflation results from an inability to grasp dynamic
      typological thinking due to the overlooked requirement to engage our cognitive
      activity in an unfamiliar way. Thus, analytical thinking alone is unsuited to
      comprehend the nature of dynamic typological thinking. Over 200 years ago, J. W.
      von Goethe, in his Metamorphosis of Plants (1790) and other writings, introduced
      a dynamic form of typological thinking that has been traditionally misunderstood
      and misrepresented. I describe in detail Goethe's phenomenological methodology
      and its contemporary value in understanding morphological patterns in living
      organisms. Furthermore, contrary to the implications of static typological
      thinking, dynamic typological thinking is perfectly compatible with evolutionary
      dynamics and, if rightly understood, can contribute significantly to the still
      emerging field of evolutionary developmental biology (evo-devo).

PMID- 23871756
TI  - Evaluation of a new rapid test kit to detect hepatitis C virus infection.
AB  - This study investigated the performance characteristics and diagnostic usefulness
      of a new rapid device test (RDT) for HCV (SD Bioline, Korea). A total of 200
      specimens were used in this study and to assess cross-reactivity, five hepatitis
      B surface antigen (HBsAg) positive, five anti-hepatitis B surface antibody (anti
      HBs) positive, five rheumatoid factor (RF) positive, and six samples from
      multiple myeloma patients were tested. The early detection capability of the test
      was assessed using seroconversion panels. Sensitivity and specificity were
      calculated compared with a recombinant immunoblot assay (RIBA). Sixty-six cases
      were positive by the RIBA, while 52 cases were positive using the new RDT. The
      sensitivity and specificity of the new RDT were 78.8% (95% CI: 71.2-86.8%) and
      100%, respectively. The kappa value for the agreement between the new RDT and
      RIBA results was 0.831 (95% CI: 0.746-0.916). The early detection capability of
      the new RDT and a HCV EIA were similar, with the same window period. The new RDT
      did not cross-react with HBsAg, anti-HBs, RF and immunoglobulins. In conclusion,
      the SD Bioline HCV RDT has superior sensitivity and specificity than the
      GENEDIA(r) HCV Rapid LF that is used in Korea. This assay can be used for HCV
      screening, especially in small hospitals, without the financial burden of
      expensive equipment.

PMID- 23871755
TI  - MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic
      diseases.
AB  - The regulation of the metabolism of cholesterol has been one of the most studied
      biological processes since its first isolation from gallstones in 1784. High
      levels of plasma low-density lipoprotein (LDL) cholesterol and reduced levels of
      plasma high-density lipoprotein (HDL) cholesterol are widely recognized as major
      risk factors of cardiovascular disease. An imbalance in the production of
      reactive oxygen species can oxidize LDL particles, increasing the levels of the
      highly proatherogenic oxidized LDL. Furthermore, under pathological scenarios,
      numerous molecules can function as pro-oxidants, such as iron or (high levels of)
      glucose. In addition to the classical mechanisms regulating lipid homeostasis,
      recent studies have demonstrated the important role of microRNAs (miRNAs) as
      regulators of lipoprotein metabolism, oxidative derivatives of lipoprotein, and
      redox balance. Here, we summarize recent findings in the field, highlighting the
      contributions of some miRNAs to lipid- and oxidative-associated pathologies. We
      also discuss how therapeutic intervention of miRNAs may be a promising strategy
      to decrease LDL, increase HDL, and ameliorate lipid- and oxidative-related
      disorders, including atherosclerosis, nonalcoholic fatty liver disease, and
      metabolic syndrome. 

PMID- 23871757
TI  - Improved detection of human papillomavirus harbored in healthy skin with
      FAP6085/64 primers.
AB  - FAP59/64, FAP6085/6319, and CUT primer sets were designed for detecting cutaneous
      HPV and have been used in many clinical and epidemiology studies. The FAP6085/64
      primer set was first evaluated in this study and the FAP6085/64 combination was
      found to be much more sensitive than all three original primer sets by using HPV
      plasmids as a template. To confirm further the effectiveness of the FAP6085/64
      primer set in human DNA templates, 90 palmar exfoliated cell DNA samples were
      used to detect the cutaneous HPV by both the FAP59/64 and FAP6085/64 primer sets.
      The overall proportion of HPV detection in those skin samples was 77.8% (70/90)
      using FAP6085/64, as compared to 55.6% (50/90) using FAP59/64. The FAP6085/64
      primer set was also applied in a population based study. The proportion of HPV
      detection was 73.96% (2076/2807) in skin samples collected from healthy
      individuals, and a total of 336 different PV types were found. Sixty (17.9%) of
      them were fully characterized HPV types, 127 (37.8%) were putative HPV types
      which had been described previously, 149 (44.3%) were novel putative HPV types,
      and two animal PVs were also detected. These results suggest that the FAP6085/64
      primer set was sensitive and effective for detection of cutaneous HPV in healthy
      skin samples. 

PMID- 23871758
TI  - Prospective analysis of Ki-67 as an independent predictor of oncologic outcomes
      in patients with high grade upper tract urothelial carcinoma.
AB  - PURPOSE: We determined the association of the proliferation marker Ki-67 with
      pathological parameters and oncologic outcomes in patients with high grade upper
      tract urothelial carcinoma. MATERIALS AND METHODS: Immunohistochemical staining
      for Ki-67 was done prospectively in 101 consecutive patients undergoing radical
      nephroureterectomy/ureterectomy for high grade upper tract urothelial carcinoma.
      Data were compared based on Ki-67 status (normal vs over expressed). Survival was
      assessed by the Kaplan-Meier method. Cox regression analysis was done to identify
      independent predictors of time dependent outcomes. RESULTS: Median patient age
      was 70.0 years and median followup was 22.0 months (range 1 to 77). Overall,
      30.2% of the population experienced recurrence and 24.8% died of upper tract
      urothelial carcinoma. Organ confined disease (T2 or less and lymph node
      negative), lymphovascular invasion and sessile architecture were present in
      56.3%, 33.3% and 20.8% of patients, respectively. Ki-67 was over expressed in
      73.3% of patients and associated with adverse pathological features. Patients
      with over expressed Ki-67 had significantly worse recurrence-free survival (43.2
      vs 69.0 months, p = 0.006) and cancer specific survival (48.9 vs 68.9 months, p =
      0.031) than patients with normal Ki-67. Patients with nonmetastatic disease
      similarly had worse recurrence-free survival (40.7 vs 71.8 months, p = 0.003) and
      cancer specific survival (41 months vs not attained, p = 0.008) for over
      expressed vs normal Ki-67. After adjusting for the effects of organ vs nonorgan
      confined disease Ki-67 over expression was an independent predictor of recurrence
      free survival in the total cohort (HR 4.3, p = 0.05) and in patients with
      nonmetastatic disease (HR 8.5, p = 0.038). CONCLUSIONS: Ki-67 over expression was
      associated with adverse pathological features in cases of upper tract urothelial
      carcinoma. It was also an independent predictor of recurrence-free survival in
      patients with high grade upper tract urothelial carcinoma.

PMID- 23871759
TI  - Military exposure and urinary incontinence among American men.
AB  - PURPOSE: We examined the association between military exposure and urinary
      incontinence in American men. MATERIALS AND METHODS: Data from the National
      Health and Nutrition Examination Survey (NHANES) from 2005 to 2008 were merged to
      include 5,297 men 20 years old or older. The question, "Did you ever serve in the
      Armed Forces of the United States?" (yes/no) was used to assess military
      exposure. Urinary incontinence was categorized as any or moderate/severe urinary
      incontinence vs none. Because the impact of military exposure varied by age,
      multivariate logistic regression models were used to estimate the OR and 95% CI
      stratified by 3 age groups, including 55 or less, 56 to 69 and 70 years or
      greater. Analysis was adjusted for race/ethnicity, education, body mass index,
      self-reported health status, number of chronic conditions, depression and
      prostate conditions, the latter in men 40 years old or older. RESULTS: Overall
      23% of male respondents reported military exposure. Men with military exposure
      were more likely to report any urinary incontinence (18.6% vs 10.4%) and
      moderate/severe urinary incontinence (9.0% vs 3.1%, each p <0.001) than men
      without military exposure. After multivariate adjustment in men 55 years old or
      younger those with military exposure had 3 times greater odds of urinary
      incontinence (OR 3.28, 95% CI 1.38-7.77). Military exposure did not increase the
      odds of urinary incontinence in men 56 to 69 years old (OR 0.97, 95% CI 0.44
      2.18), or 70 years old or older (OR 0.91, 95% CI 0.55-1.50). CONCLUSIONS: Prior
      military exposure was associated with moderate/severe urinary incontinence in
      American men 55 years old or younger even after controlling for known risk
      factors. Case finding is warranted for urinary incontinence in younger men with a
      history of military service.

PMID- 23871760
TI  - Control of smooth muscle alpha-actin (SMA) up-regulation in HBMSCs using remote
      magnetic particle mechano-activation.
AB  - Physical cues have the potential to guide stem cell fate by coupling a mechanical
      stimulus to biochemical signaling. We have postulated that mechanical stimulation
      could provide a control method for cell therapy applications. This study
      investigates the use of functionalized magnetic nanoparticles to promote hBMSC
      differentiation towards a smooth muscle cell lineage by direct mechanical
      stimulation of platelet-derived growth factor receptor alpha and beta (PDGFRalpha
      and beta) via exposure to time-varying magnetic fields. Cyclical magneto
      mechanical stimulation of PDGFR alpha over a 3h period results in up-regulation
      of smooth muscle alpha-actin expression in both protein and mRNA level.
      PDGFRalpha phosphorylation is detected in response to stimulation and the mRNA up
      regulation is abrogated by pretreatment of cells with a receptor inhibitor,
      AG1296 or the neutralization antibody. Our results demonstrate proof of concept
      for remote controlled, locally-delivered mechanically induced differentiation of
      hBMSCs which could have applications in regenerative medicine. FROM THE CLINICAL
      EDITOR: Using a cyclical magneto-mechanical stimulator, this team of
      investigators demonstrated successful differentiation induction of human bone
      marrow-derived stem cells toward smooth muscle protein expression, with potential
      future applications in regenerative medicine.

PMID- 23871761
TI  - Nanomaterials in combating cancer: therapeutic applications and developments.
AB  - The development of novel nanomaterials and their use in biomedicine has received
      much attention in recent years. Significant advances have been made in the
      synthesis of nanomaterials with controlled geometry, physicochemical properties,
      surface charge, and surface tailoring with bioactive polymers. These successful
      efforts have resulted in improved biocompatibility and active targeting of tumour
      tissues, leading to the development of a diverse range of nanomaterials that can
      recognize cancers, deliver anticancer drugs and destroy tumours by a variety of
      therapeutic techniques. The focus of this review is to provide an overview of the
      nanomaterials that have been devised for the detection and treatment of various
      types of cancer, as well as to underline the emerging possibilities of
      nanomaterials for applications in anticancer therapy. FROM THE CLINICAL EDITOR:
      In this comprehensive review, the current state-of-the art of nanomaterials for
      cancer diagnosis and treatment is presented. Emerging possibilities and future
      concepts are discussed as well.

PMID- 23871762
TI  - Imaging horse tendons using multimodal 2-photon microscopy.
AB  - Injuries and damage to tendons plague both human and equine athletes. At the site
      of injuries, various cells congregate to repair and re-structure the collagen.
      Treatments for collagen injury range from simple procedures such as icing and
      pharmaceutical treatments to more complex surgeries and the implantation of stem
      cells. Regardless of the treatment, the level of mechanical stimulation incurred
      by the recovering tendon is crucial. However, for a given tendon injury, it is
      not known precisely how much of a load should be applied for an effective
      recovery. Both too much and too little loading of the tendon could be detrimental
      during recovery. A mapping of the complex local environment imparted to any cell
      present at the site of a tendon injury may however, convey fundamental insights
      related to their decision making as a function of applied load. Therefore,
      fundamentally knowing how cells translate mechanical cues from their external
      environment into signals regulating their functions during repair is crucial to
      more effectively treat these types of injuries. In this paper, we studied systems
      of tendons with a variety of 2-photon-based imaging techniques to examine the
      local mechanical environment of cells in both normal and injured tendons. These
      tendons were chemically treated to instigate various extents of injury and in
      some cases, were injected with stem cells. The results related by each imaging
      technique distinguish with high contrast and resolution multiple morphologies of
      the cells' nuclei and the alignment of the collagen during injury. The
      incorporation of 2-photon FLIM into this study probed new features in the local
      environment of the nuclei that were not apparent with steady-state imaging.
      Overall, this paper focuses on horse tendon injury pattern and analysis with
      different 2-photon confocal modalities useful for wide variety of application in
      damaged tissues. 

PMID- 23871763
TI  - Global brain hypoperfusion and oxygenation in amnestic mild cognitive impairment.
AB  - BACKGROUND: To determine if global brain hypoperfusion and oxygen hypometabolism
      occur in patients with amnestic mild cognitive impairment (aMCI). METHODS: Thirty
      two aMCI and 21 normal subjects participated. Total cerebral blood flow (TCBF),
      cerebral metabolic rate of oxygen (CMRO2), and brain tissue volume were measured
      using color-coded duplex ultrasonography (CDUS), near-infrared spectroscopy
      (NIRS), and MRI. TCBF was normalized by total brain tissue volume (TBV) for group
      comparisons (nTCBF). Cerebrovascular resistance (CVR) was calculated as mean
      arterial pressure divided by TCBF. RESULTS: Reductions in nTCBF by 9%, CMRO2 by
      11%, and an increase in CVR by 13% were observed in aMCI relative to normal
      subjects. No group differences in TBV were observed. nTCBF was correlated with
      CMRO2 in normal controls, but not in aMCI. CONCLUSIONS: Global brain
      hypoperfusion, oxygen hypometabolism, and neurovascular decoupling observed in
      aMCI suggest that changes in cerebral hemodynamics occur early at a prodromal
      stage of Alzheimer's disease, which can be assessed using low-cost and bedside
      available CDUS and NIRS technology.

PMID- 23871764
TI  - Reduced 25-hydroxyvitamin D and risk of Alzheimer's disease and vascular
      dementia.
AB  - BACKGROUND: Vitamin D deficiency has been implicated as a risk factor for
      dementia in several cross-sectional studies. We tested the hypothesis that
      reduced plasma 25-hydroxyvitamin D (25[OH]D) is associated with increased risk of
      Alzheimer's disease (AD) and vascular dementia in the general population.
      METHODS: We measured baseline plasma 25(OH)D in 10,186 white individuals from the
      Danish general population. RESULTS: During 30 years of follow-up, 418
      participants developed AD and 92 developed vascular dementia. Multivariable
      adjusted hazard ratios for AD were 1.25 (95% confidence interval [CI], 0.95-1.64)
      for 25(OH)D less than 25 nmol/L vs. greater than or equal to 50 nmol/L, and 1.29
      (95% CI, 1.01-1.66) for less than the 25th seasonally adjusted 25(OH)D percentile
      vs. more than the 50th seasonally adjusted 25(OH)D percentile. Multivariable
      adjusted hazard ratios for vascular dementia were 1.22 (95% CI, 0.77-1.91) for
      25(OH)D less than 50 nmol/L vs. greater than or equal to 50 nmol/L, and 1.22 (95%
      CI, 0.79-1.87) for less than or equal to the 50th vs. more than the 50th
      seasonally adjusted 25(OH)D percentile. Last, multivariable adjusted hazard
      ratios for the combined end point were 1.28 (95% CI, 1.00-1.64) for 25(OH)D less
      than 25 nmol/L vs. greater than or equal to 50 nmol/L, and 1.27 (95% CI, 1.01
      1.60) for less than the 25th vs. more than the 50th seasonally adjusted 25(OH)D.
      CONCLUSIONS: We observed an association of reduced plasma 25(OH)D with increased
      risk of the combined end point of AD and vascular dementia in this prospective
      cohort study of the general population.

PMID- 23871765
TI  - The prevalence of dementia in urban and rural areas of China.
AB  - OBJECTIVE: The Chinese population has been aging rapidly and the country's
      economy has experienced exponential growth during the past three decades. The
      goal of this study was to estimate the changes in the prevalence of dementia,
      Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese
      individuals and to analyze differences between urban and rural areas. METHODS:
      For the years 2008 to 2009, we performed a population-based cross-sectional
      survey with a multistage cluster sampling design. Residents aged 65 years and
      older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities
      across China. Participants were assessed with a series of clinical examinations
      and neuropsychological measures. Dementia, AD, and VaD were diagnosed according
      to established criteria via standard diagnostic procedures. RESULTS: The
      prevalence of dementia, AD, and VaD among individuals aged 65 years and older
      were 5.14% (95% CI, 4.71-5.57), 3.21% (95% CI, 2.87-3.55), and 1.50% (95% CI,
      1.26-1.74), respectively. The prevalence of dementia was significantly higher in
      rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional
      difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD
      (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample
      was stratified by educational level. Moreover, the risk factors for AD and VaD
      differed for urban and rural populations. CONCLUSIONS: A notably higher
      prevalence of dementia and AD was found in rural areas than in urban ones, and
      education might be an important reason for the urban-rural differences.

PMID- 23871767
TI  - Whole genome sequencing and the prevention and control of meticillin-resistant
      Staphylococcus aureus infection.

PMID- 23871766
TI  - A quantitative morphological analysis of the inner ear of galliform birds.
AB  - The function of the inner ear is dependent on its physical structure and there is
      therefore a strong correspondence between inner ear morphology and hearing
      capabilities. In this study, we examine the morphology of the inner ear and use
      this relationship to predict the hearing range and sensitivities of species
      within the Order Galliformes (chicken, quail and allies). All galliforms share a
      similar inner ear morphology, which is characterized by gradients in hair cell
      morphology that are similar to other birds. Most galliforms did have an area of
      morphologically similar hair cells at the apical end of the BP, indicative of a
      low frequency specialization. We suggest that, in general, the galliform inner
      ear is tuned for detecting low frequencies, with most hair cells and more than
      half of the BP dedicated to frequencies below 1 kHz. Whether this is a
      specialization or associated with their basal lineage remains to be determined.
      We also determined that body and brain size are associated with the number of
      hair cells and basilar papilla length across galliform birds, such that as body
      size increases, there are correlated increases in BP length and the number of
      hair cells. Our data therefore corroborate patterns observed across a wide range
      of bird species and provides significant insight into how species differences in
      BP morphology evolve and putative relationships with size, vocalizations and life
      history. 

PMID- 23871768
TI  - Screening for meticillin-resistant Staphylococcus aureus: targeted not universal
      screening.

PMID- 23871769
TI  - The role of MGMT testing in clinical practice: a report of the association for
      molecular pathology.
AB  - Recent advances in modern molecular technologies allow for the examination and
      measurement of cancer-related genomic changes. The number of molecular tests for
      evaluation of diagnostic, prognostic, or predictive markers is expected to
      increase. In recent years, O(6)-methylguanine-DNA methyltransferase (MGMT)
      promoter methylation has been firmly established as a biomarker in patients
      diagnosed with gliomas, for both clinical trials and routine clinical management.
      Similarly, molecular markers, such as loss of heterozygosity (LOH) for 1p/19q
      have already demonstrated clinical utility in treatment of oligodendroglial
      tumors, and others might soon show clinical utility. Furthermore, nonrandom
      associations are being discovered among MGMT, 1p/19q LOH, isocitrate
      dehydrogenase (IDH) mutations, and other tumor-specific modifications that could
      possibly enhance our ability to predict outcome and response to therapy. While
      pathologists are facing new and more complicated requests for clinical genomic
      testing, clinicians are challenged with increasing numbers of molecular data
      coming from molecular pathology and genomic medicine. Both pathologists and
      oncologists need to understand the clinical utility of molecular tests and test
      results, including issues of turnaround time, and their impact on the application
      of targeted treatment regimens. This review summarizes the existing data that
      support the rationale for MGMT promoter methylation testing and possibly other
      molecular testing in clinically defined glioma subtypes. Various molecular
      testing platforms for evaluation of MGMT methylation status are also discussed. 

PMID- 23871770
TI  - Caution regarding the interpretation of homoallelism in polyglutamine multiplex
      assays: a recommendation for confirmatory testing of homozygous alleles.
AB  - Spinocerebellar ataxia type 7 (SCA7) is an inherited dominant neurodegenerative
      disease caused by the expansion of a CAG repeat within the ATXN7 gene. Standard
      molecular diagnostic testing for SCA7 involves amplification of the region
      surrounding the CAG repeat via end-labeled PCR and subsequent capillary
      electrophoresis. In addition, multiplex methods exist that may be used to test
      for multiple polyglutamine spinocerebellar ataxias in a single assay. Herein, we
      used a SCA7 singleplex method to screen 111 individuals for whom the multiplex
      method detected a single normal allele. A total of six retested individuals
      (5.4%) were shown to have a pathogenic expansion at the ATXN7 locus. An
      additional triplet-primed PCR method was used to test the same cohort, and
      revealed no further disease-causing alleles. This study demonstrates the
      importance of using complementary methods to rule out apparent homoallelism
      during molecular testing for polyglutamine diseases. 

PMID- 23871771
TI  - Positive selection signals of hepatitis B virus and their association with
      disease stages and viral genotypes.
AB  - The hepatitis B virus (HBV) is a global health problem that causes different
      types of liver diseases. The high mutation rate of HBV, which results from a lack
      of proofreading activity of the viral polymerase, leads to the actively adaptive
      evolution of mutant strains under various selection pressures. This study focuses
      on the positive selection signals in the whole HBV genome and the association of
      these selection signals with the disease stages and/or viral genotypes. A total
      of 486 complete HBV genomes from HBV-infected individuals of different illness
      categories (i.e., acute, chronic, and severe hepatitis) were analyzed. To obtain
      a panoramic view of the selection signals, codon-based maximum likelihood
      analysis, three-dimensional (3D) mapping, and allele frequency comparison were
      conducted on genotypes B and C HBV from subjects with different stages of
      hepatitis. A total of 95 selected codons were resolved, and a significantly
      higher number of positive selection signatures were found in the chronic and
      severe hepatitis groups compared with the acute groups. Many of the selected
      codons were associated with either a unique disease stage or a specific genotype.
      The conservation analysis of the selection signals in the viral core protein
      (HBcAg) illustrated the occurrence of selected codons in the highly diversified
      regions. The allele-frequency-based analysis identified eight additional
      nucleotide substitutions, and the frequencies of these mutations were found to
      increase with disease progression. Moreover, we found that three substitutions,
      including A1762T, G1764A, and A2739C, were nearly fixed. The mapping of all of
      the selected codons and nucleotide substitutions to the functional domains of the
      viral proteins suggested that more than 60% of the mutations were subject to
      selection forces from host immune surveillance, antiviral therapy, and
      replication fitness. 

PMID- 23871772
TI  - Hepatitis G virus/GBV-C in serum, peripheral blood mononuclear cells and bone
      marrow in patients with hematological malignancies.
AB  - BACKGROUND: HGV/GBV-C is highly prevalent in the general population but its
      significance remains unclear. It is known that HGV/GBV-C is not primary
      hepatotropic and its replication was reported in PBMC, bone marrow and other
      tissues. To investigate a possible role of HGV/GBV-C 115 consecutive patients
      with hematological malignancies were analyzed for virus RNA presence and
      quasispecies composition in three compartments: serum, PBMC and bone marrow.
      METHODS: RT-PCR was used to amplify 5'UTR HGV/GBV-C in serum, PBMC and bone
      marrow. Viral sequences obtained from three compartments were subjected for
      comparative molecular analysis performed by single strand conformational
      polymorphism (SSCP) and pyrosequencing. RESULTS: HGV/GBV-C RNA was detected in 23
      out of 115 (20.0%) patients, most often in bone marrow (18 patients), followed by
      PBMC (11 patients) and serum (10 patients). Differences in SSCP bands
      distribution corresponding to different viral variants and confirmed by direct
      sequencing were observed in three patients. CONCLUSION: HGV/GBV-C infection is
      frequent in patients with hematological malignancies. Common detection of HGV/GBV
      C in bone marrow supports the hypothesis that it is a major replication site of
      this virus.

PMID- 23871773
TI  - "Omics" in the study of the major parasitic diseases malaria and schistosomiasis.
AB  - Genomic, transcriptomic, proteomic, and metabolomic projects exemplify the
      "omics" era, and have significantly expanded available data for biomedical
      research. Recently, next generation sequencing technologies have even more
      greatly expanded DNA and RNA information. The present challenge is mining this
      information to obtain meaningful data such as that identifying novel drug targets
      and vaccine candidates. Several bioinformatics tools and new technologies have
      been used to high-throughput identification of potential candidates. We
      illustrate the utilization of new strategies in the study of two major parasitic
      diseases: schistosomiasis and malaria. 

PMID- 23871775
TI  - Genetic and evolutionary analysis of cell-fusing agent virus based on Thai
      strains isolated in 2008 and 2012.
AB  - Increasing attention is being devoted to ecological and evolutionary
      relationships between insect-specific flaviviruses and globally important human
      pathogenic flaviviruses such as dengue viruses. One such insect flavivirus, cell
      fusing agent virus (CFAV), remains poorly investigated. In this study, we
      isolated 13 and 16 CFAV strains from Aedes aegypti mosquitoes collected in
      Thailand in 2008 and 2012, respectively, and performed genetic and evolutionary
      analyses based on gene regions encoding the envelope protein (E) and
      nonstructural proteins 3 (NS3) and 5 (NS5). Consistent with previously reported
      CFAV strains, E, NS3 and NS5 regions comprised 1,290, 1,761 and 2,664
      nucleotides, respectively. Nucleotide and amino acid identities of these three
      regions were >98% among the 29 isolates, and approximately 95-96% and 96-99%,
      respectively, between the isolates and previously reported CFAV strains. When
      amino acid sequences from representative strains of six insect-specific and seven
      mosquito-borne flaviviruses were compared, average identities of 14.9%, 31.8% and
      44.3% were calculated for E, NS3 and NS5 regions, respectively. Phylogenetic
      analysis based on nucleotide and amino acid data indicated that the Thai CFAV
      isolates of the current study were distinct from previously reported CFAV strains
      from Indonesia and Puerto Rico. Analysis of each gene region consistently
      uncovered a clade made up of nearly the same subset of Thai CFAV isolates; this
      result, and the isolation of CFAV from mosquitoes reared from larvae, suggest
      that the virus is maintained by vertical transmission and conserved in a
      particular environment without considerable evolutionary alteration. The most
      recent common ancestor of the Thai CFAV isolates in this study was dated to 11-27
      years ago, and is estimated to have diverged 46-86 years ago from previously
      reported CFAV strains. Superinfection with CFAV of Aedes mosquitoes carrying
      dengue viruses present in Thailand for over 50 years has most likely taken place.

PMID- 23871774
TI  - Microsatellite analysis of chloroquine resistance associated alleles and neutral
      loci reveal genetic structure of Indian Plasmodium falciparum.
AB  - Efforts to control malignant malaria caused by Plasmodium falciparum are hampered
      by the parasite's acquisition of resistance to antimalarial drugs, e.g.,
      chloroquine. This necessitates evaluating the spread of chloroquine resistance in
      any malaria-endemic area. India displays highly variable malaria epidemiology and
      also shares porous international borders with malaria-endemic Southeast Asian
      countries having multi-drug resistant malaria. Malaria epidemiology in India is
      believed to be affected by two major factors: high genetic diversity and evolving
      drug resistance in P. falciparum. How transmission intensity of malaria can
      influence the genetic structure of chloroquine-resistant P. falciparum population
      in India is unknown. Here, genetic diversity within and among P. falciparum
      populations is analyzed with respect to their prevalence and chloroquine
      resistance observed in 13 different locations in India. Microsatellites developed
      for P. falciparum, including three putatively neutral and seven microsatellites
      thought to be under a hitchhiking effect due to chloroquine selection were used.
      Genetic hitchhiking is observed in five of seven microsatellites flanking the
      gene responsible for chloroquine resistance. Genetic admixture analysis and F
      statistics detected genetically distinct groups in accordance with transmission
      intensity of different locations and the probable use of chloroquine. A large
      genetic break between the chloroquine-resistant parasite of the Northeast-East
      Island group and Southwest group (FST=0.253, P<0.001) suggests a long period of
      isolation or a possibility of different origin between them. A pattern of
      significant isolation by distance was observed in low transmission areas (r=0.49,
      P=0.003, N=83, Mantel test). An unanticipated pattern of spread of hitchhiking
      suggests genetic structure for Indian P. falciparum population. Overall, the
      study suggests that transmission intensity can be an efficient driver for genetic
      differentiation at both neutral and adaptive loci across India. 

PMID- 23871776
TI  - Molecular epidemiology and genetic diversity of hepatitis B virus in Mar del
      Plata city, Argentina.
AB  - The aim of this work was to describe the current molecular epidemiology and
      genetic diversity of HBV in Mar del Plata, an important Argentinean touristic
      city. The phylogenetic analysis of 29 HBV DNA positive serum samples showed that
      F1b was the predominant subgenotype (sgt, 62.1%), followed by sgt A2 (13.8%) and
      sgt F4, gt D and gt G (6.9% each). Among anti-HBc IgM positive samples, 75.0%
      were sgt F1b, followed by sgt F4 (12.5%), sgt A2 (6.25%) and sgt D (6.25%). Three
      recombinant full length genomes were found: two G/F1b (some of the first gt G
      detected in Argentina) and one F4/D2. The circulation of clinical important
      mutations in the city was described. Mutations at the HBsAg were detected in
      34.5% of the analyzed samples, associated with laboratory diagnosis and antiviral
      treatment failures, immune escape and hepatocellular carcinoma. Most of the
      samples presented wild type BCP/PC sequences. Coalescence analysis for the most
      prevalent sgt F1b estimated that the diversification mainly occured during mid
      '90s and the tMRCA was estimated in 1987. Finally, the high presence of the
      autochthonous sgt F1b, associated with the anti-HBc IgM positive infection and
      its present-day diversification process, shows the strong impact of internal
      human migratory movements into the current population of Mar del Plata. 

PMID- 23871777
TI  - Yolk androstenedione in domestic chicks (Gallus gallus domesticus): uptake and
      sex-dependent alteration of growth and behavior.
AB  - In birds, causes and consequences of variation in maternally-derived steroids in
      egg yolk have been the subject of intense experimentation. Many studies have
      quantified or manipulated testosterone ("T") and one of its immediate precursors,
      androstenedione ("A4") - often lumping the two steroids as "androgens" and
      treating them as functionally equivalent. However, yolk A4 is deposited in
      substantially higher concentrations than T, binds only weakly to the androgen
      receptor, and is readily converted into either T or estrone by steroidogenic
      enzymes present during embryonic development. Thus it may not be appropriate to
      assume that A4 has the same effect as T. In addition, A4's metabolic fate is
      likely to differ between females and males. The goals of this study were to
      examine the sex-specific uptake and metabolism of yolk A4 and consequences of
      elevated levels of yolk A4 on development and behavior of domestic chicks. Eggs
      were injected with 2MU Ci of tritiated androstenedione; radioactivity was
      detected in all tissues of day 7 and day 16 embryos and found in both aqueous and
      organics phases of day 7 yolk, with no difference between sexes. A second set of
      eggs was injected with 125ng of A4. A4 increased growth of morphological traits
      (tarsus, beak) in females, but not males. A4 males had smaller combs than
      controls; there was no treatment effect in females. A4 reduced tonic immobility
      behavior in both sexes. The results of this study illustrate the importance of
      distinguishing both between androgens and between sexes when investigating avian
      endocrine maternal effects. 

PMID- 23871778
TI  - GPER mediates the inhibitory actions of estrogen on adipogenesis in 3T3-L1 cells
      through perturbation of mitotic clonal expansion.
AB  - G-protein-coupled estrogen receptor 1 (GPER) mediates non-genomic signaling of
      estrogenic events. Here we showed for the first time that Gper/GPER is expressed
      in Swiss 3T3 mouse embryo preadipocytes 3T3-L1, and that Gper/GPER is up
      regulated during differentiation of the cells induced by monocyte differentiation
      inducing (MDI) cocktail. Activation of GPER by the natural ligand 17beta
      estradiol (E2), and the specific agonist G1, was shown to inhibit lipid
      accumulation in 3T3-L1 cells, while such inhibition was reversed upon knockdown
      of GPER using specific siRNA. GPER was also found to mediate perturbation of
      mitotic clonal expansion (MCE) in these cells by inhibiting cell cycle arrest
      during MDI cocktail-induced differentiation. Persistent activation of cell cycle
      regulating factors cyclin-dependant kinase (CDK) 4, CDK6 and cyclin D1, and
      phosphorylation of retinoblastoma (Rb) protein at serine 795 was observed in the
      G1-treated cells. Taken together, our results indicate that E2-GPER signaling
      leads to an inhibition of adipogenesis in 3T3-L1 cells via perturbation of MCE. 

PMID- 23871779
TI  - Allogeneic hematopoietic cell transplantation in septuagenarians.

PMID- 23871780
TI  - Absence of post-transplantation lymphoproliferative disorder after allogeneic
      blood or marrow transplantation using post-transplantation cyclophosphamide as
      graft-versus-host disease prophylaxis.
AB  - Immunosuppressive regimens that effectively prevent graft-versus-host disease
      (GVHD) after allogeneic blood or marrow transplantation (allo-BMT) have been
      associated with an increased incidence of post-transplantation
      lymphoproliferative disorder (PTLD) in the first year after transplantation. We
      evaluated the incidence of PTLD associated with the use of high-dose post
      transplantation cyclophosphamide (PTCy) as GVHD prophylaxis. Between 2000 and
      2011, a total of 785 adult allo-BMT recipients were given PTCy as GVHD
      prophylaxis at the Johns Hopkins Hospital, including 313 patients who received
      PTCy as sole GVHD prophylaxis. HLA-haploidentical or unrelated donor graft
      transplantation was performed in 526 patients (67%). No cases of PTLD occurred
      during the first year after allo-BMT in this series. PTLD is a rare occurrence
      after allo-BMT using PTCy, even in high-risk alternative donor transplantations. 

PMID- 23871781
TI  - Establishing a target exposure for once-daily intravenous busulfan given with
      fludarabine and thymoglobulin before allogeneic transplantation.
AB  - A combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated
      and effective in patients undergoing allogeneic hematopoietic stem cell
      transplantation. Although there is some evidence that Bu exposures exceeding 6000
      MUM.min [corrected] may lead to excessive toxicity, there is little information
      on the effect of exposures below this level on outcomes. We studied Bu exposure,
      as measured by area under the concentration-time curve (AUC), in 158 patients
      with various hematologic malignancies in an attempt to identify an optimal range
      for targeted therapy. The preparative chemotherapy regimen comprised Flu 50
      mg/m(2) on days -6 to -2 and i.v. Bu 3.2 mg/kg on days -5 to -2 inclusive. Graft
      versus-host disease (GVHD) prophylaxis included methotrexate, cyclosporin A, and
      antithymocyte globulin. Patients with Bu exposures below the median AUC of 4439
      MUM.min [corrected] were at increased risk for acute GVHD grade II-IV (hazard
      ratio [HR], 2.30; 95% confidence interval [CI], 1.19 to 4.49; P = .014). Those in
      the highest and lowest Bu exposure quartiles (daily AUC <3814 MUM.min and >4993
      MUM.min) [corrected] had an increased risk of nonrelapse mortality
      (subdistribution HR, 3.32; 95% CI, 1.46 to 7.54; P = .004), as well as worse
      disease-free survival (HR, 1.81; 95% CI, 1.09 to 2.99; P = .021) and overall
      survival (HR, 1.94; 95% CI, 1.12 to 3.37; P = .018). Bu exposures between 4440
      and 4993 MUM/min were accompanied by the lowest risk of both nonrelapse mortality
      and acute GVHD.

PMID- 23871782
TI  - Specific features identify patients with relapsed or refractory mantle cell
      lymphoma benefitting from autologous hematopoietic cell transplantation.
AB  - Outcomes with autologous hematopoietic cell transplantation (auto HCT) for
      relapsed and/or refractory mantle cell lymphoma (MCL) are typically poor. We
      hypothesized that certain factors could predict which patients experience a
      favorable outcome with this approach. We thus developed a predictive score from a
      cohort of 67 such patients using 3 factors independently associated with
      progression-free survival (PFS): (1) simplified Mantle Cell Lymphoma
      International Prognostic Index score before auto HCT (hazard ratio [HR], 2.9; P =
      .002); (2) B symptoms at diagnosis (HR, 2.7; P = .005); and (3) remission
      quotient, calculated by dividing the time, in months, from diagnosis to auto HCT
      by the number of prior treatments (HR, 1.4; P = .02). The estimated 5-year PFS
      for favorable-risk patients (n = 23) and unfavorable-risk patients (n = 44) were
      58% (95% confidence interval [CI], 34% to 75%) and 15% (95% CI, 6% to 28%),
      respectively. These factors also independently predicted overall survival. In
      summary, we have defined 3 simple factors that can identify patients with
      relapsed/refractory MCL who derive a durable benefit from salvage auto HCT.

PMID- 23871783
TI  - Interactions between dietary flavonoids apigenin or luteolin and chemotherapeutic
      drugs to potentiate anti-proliferative effect on human pancreatic cancer cells,
      in vitro.
AB  - The objectives were to assess the potential of dietary flavonoids apigenin (Api)
      and luteolin (Lut) to enhance the anti-proliferative effects of chemotherapeutic
      drugs on BxPC-3 human pancreatic cancer cells and to investigate the potential
      molecular mechanism of action. Simultaneous treatment or pretreatment (0, 6, 24
      and 42 h) of flavonoids and chemotherapeutic drugs at various concentrations (0
      50 MUM) were assessed using the MTS cell proliferation assay. Simultaneous
      treatment with either flavonoid (13, 25 or 50 MUM) and chemotherapeutic drugs 5
      fluorouracil (5-FU, 50 MUM) or gemcitabine (Gem, 10 MUM) for 60 h resulted in
      mostly less-than-additive effects (p<0.05). Pretreatment for 24h with 13 MUM of
      either Api or Lut, followed by Gem for 36 h was optimal to inhibit cell
      proliferation. Pretreatment of cells with 11-19 MUM of either flavonoid for 24h
      resulted in 59-73% growth inhibition when followed by Gem (10 MUM, 36 h). Lut (15
      MUM, 24h) pretreatment followed by Gem (10 MUM, 36 h), significantly decreased
      protein expression of nuclear GSK-3beta and NF-kappaB p65 and increased pro
      apoptotic cytosolic cytochrome c. Pretreatment of BxPC-3 human pancreatic cancer
      cells with low concentrations of Api or Lut effectively aid in the anti
      proliferative activity of chemotherapeutic drugs.

PMID- 23871784
TI  - Acute and 13 weeks subchronic toxicological evaluation of naringin in Sprague
      Dawley rats.
AB  - Naringin is widely distributed in plant foods and has not previously been
      evaluated for safety through standard in vivo toxicological studies. In the
      present study, acute and subchronic oral toxicity studies of naringin were
      designed and conducted in Sprague-Dawley (SD) rats. Acute oral administration of
      naringin was done as a single bolus dose up to 16 g/kg and subchronic toxicity
      study for 13 weeks was done by oral administration at doses of 0 (control), 50,
      250 and 1250 mg/kg in SD rats. There were no mortality, adverse clinical signs,
      abnormal changes in body weights or food consumption, toxicologically relevant
      changes in hematology, clinical biochemistry and macroscopic findings during 14
      days of the acute toxicity study. During the subchronic oral toxicity study, no
      mortality and toxicologically significant changes in clinical signs, food
      consumption, opthalmoscopic examination, hematology, clinical biochemistry, serum
      sex hormone, macroscopic findings, organ weights and histopathological
      examination except for slight body weight decrease were noted and attributed to
      naringin administration. These observations suggest that naringin is practically
      non-toxic for SD rats in oral acute toxicity study and the no-observed-adverse
      effect-level (NOAEL) of naringin in rats is greater than 1250 mg/kg/day when
      administered orally for 13 consecutive weeks.

PMID- 23871785
TI  - Modulation of antioxidant defense system by the dithiocarbamate fungicides Maneb
      and Zineb in Chinese hamster V79 cells and the role of N-acetyl-L-cysteine.
AB  - Oxidative stress is one of the major factors leading to Maneb- and Zineb-induced
      disorders. The aim of this in vitro study was to examine (i) the potency of Maneb
      and Zineb to induce changes in antioxidant enzyme activities in Chinese hamster
      fibroblasts V79 cells and (ii) the role of N-acetyl-L-cysteine (NAC) in the
      preventing their action. Maneb increased mitochondrial superoxide dismutase
      (SOD2) activity but failed to affect the activity of cytoplasmic superoxide
      dismutase (SOD1), whereas Zineb did not change the activity of any of superoxide
      dismutases. The activity of catalase (CAT) was reduced only by Zineb. The
      activity of both glutathione peroxidases (non-Se-GPx, Se-GPx) and glutathione
      reductase (GR) was decreased after exposure to these agents. After NAC pre
      treatment Maneb increased the activity of GR, whereas the activity of non-Se-GPx
      was decreased as compared to that in NAC-treated cells. On the other hand, the
      activity of both SODs and CAT was decreased. Zineb decreased the activity of both
      GPxs and SOD2 with a concomitant increase in CAT activity comparing to NAC
      treated cells. The results obtained thus suggest that Zineb acts by another
      mechanism, than Maneb does, and that one of the mechanisms of NAC protection
      against Maneb or Zineb-induced effects in V79 cells is its impact on enzymatic
      defense. Activity of GR, SOD2, and GPxs are the most affected enzymes. 

PMID- 23871786
TI  - Pubertal exposure to Bisphenol A increases anxiety-like behavior and decreases
      acetylcholinesterase activity of hippocampus in adult male mice.
AB  - The negative effects of Bisphenol A (BPA) on neurodevelopment and behaviors have
      been well established. Acetylcholinesterase (AChE) is a regulatory enzyme which
      is involved in anxiety-like behavior. This study investigated behavioral
      phenotypes and AChE activity in male mice following BPA exposure during puberty.
      On postnatal day (PND) 35, male mice were exposed to 50mg BPA/kg diet per day for
      a period of 35 days. On PND71, a behavioral assay was performed using the
      elevated plus maze (EPM) and the light/dark test. In addition, AChE activity was
      measured in the prefrontal cortex, hypothalamus, cerebellum and hippocampus.
      Results from our behavioral phenotyping indicated that anxiety-like behavior was
      increased in mice exposed to BPA. AChE activity was significantly decreased in
      the hippocampus of mice with BPA compared to control mice, whereas no difference
      was found in the prefrontal cortex, hypothalamus and cerebellum. Our findings
      showed that pubertal BPA exposure increased anxiety-like behavior, which may be
      associated with decreased AChE activity of the hippocampus in adult male mice.
      Further studies are necessary to investigate the cholinergic signaling of the
      hippocampus in PBE induced anxiety-like behaviors.

PMID- 23871787
TI  - Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in
      experimental mice through activation of Nrf2 pathway, promotion of arsenic
      methylation and urinary excretion.
AB  - Oxidative stress is one of the major mechanisms implicated in inorganic arsenic
      poisoning. Curcumin is a natural phenolic compound with impressive antioxidant
      properties. What's more, curcumin is recently proved to exert its chemopreventive
      effects partly through the activation of nuclear factor (erythroid-2 related)
      factor 2 (Nrf2) and its antioxidant and phase II detoxifying enzymes. In vivo, we
      investigated the protective effects of curcumin against arsenic-induced
      hepatotoxicity and oxidative injuries. Our results showed that arsenic-induced
      elevation of serum alanine amino transferase (ALT) and aspartate aminotransferase
      (AST) activities, augmentation of hepatic malonaldehyde (MDA), as well as the
      reduction of blood and hepatic glutathione (GSH) levels, were all consistently
      relieved by curcumin. We also observed the involvement of curcumin in promoting
      arsenic methylation and urinary elimination in vivo. Furthermore, both the
      hepatic Nrf2 protein and two typically recognized Nrf2 downstream genes, NADP(H)
      quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), were consistently up
      regulated in curcumin-treated mice. Our study confirmed the antagonistic roles of
      curcumin to counteract inorganic arsenic-induced hepatic toxicity in vivo, and
      suggested that the potent Nrf2 activation capability might be valuable for the
      protective effects of curcumin against arsenic intoxication. This provides a
      potential useful chemopreventive dietary component for human populations. 

PMID- 23871788
TI  - Artocarpin attenuates ultraviolet B-induced skin damage in hairless mice by
      antioxidant and anti-inflammatory effect.
AB  - Artocarpin, a prenylated flavonoid isolated from an agricultural plant Artocarpus
      communis, has been documented to possess anti-inflammation and anticancer
      activities. As oxidative stress and inflammation promote the development of
      ultraviolet B (UVB) irradiation-induced photodamage, the aim of the present study
      was to evaluate the photoprotective effect of artocarpin on UVB-induced skin
      damage in hairless mice. Artocarpin at a topical dose of 0.05% and 0.1% showed a
      significant photoprotective effect by decreasing histopathological changes, such
      as desquamation, epidermal thicken and sunburn cell formation, but 0.1% of
      artocarpin administration did not show better effect. Regarding the antioxidant
      activities, artocarpin exhibited a significant effect (P<0.05) by decreasing
      levels of reactive species oxygen and lipid peroxidation. In addition, artocarpin
      can significant decrease the level of tumor necrosis factor-alpha and interleukin
      1beta for downregulating the inflammation protein, including the synthesis of
      cytosolic phospholipase A2 and cyclooxygenase-2 (P<0.05). In conclusion, these
      data suggest that artocarpin can prevent skin damage from UVB irradiation-induced
      photodamage in hairless mice and this is likely mediated through its antioxidant
      and anti-inflammation mechanisms. Therefore, we suggested that artocarpin could
      be a useful photoprotective agent in medicine and/or cosmetics.

PMID- 23871791
TI  - Posttranslational modifications of cardiac troponin T: an overview.
AB  - Cardiac troponin (cTn) is an important sarcomeric protein complex situated on the
      thin filament and is involved in the regulation of cardiac muscle contraction.
      This regulation is primarily controlled by Ca(2+) binding to troponin C and in
      addition fine-tuned by the posttranslational modification of cTnI and cTnT. The
      vast majority of cTnT modifications involve the phosphorylation by protein kinase
      C (PKC) or other kinases and the N-terminal cleavage by caspase and calpain. In
      vitro studies employing reconstituted detergent-skinned fiber bundles and cell
      culture generally show a detrimental effect of cTnT phosphorylation on muscle
      contraction, which is backed by some in vivo studies finding increased cTnT
      phosphorylation in heart failure, but contradicted by others. In addition, N
      terminal cleavage of cTnT is thought to be another factor influencing cardiac
      contraction. Time-dependent degradation of cTnT has been observed in human serum
      upon myocardial infarction. These molecular changes might influence the
      immunoreactivity of cTnT in the clinical immunoassay and have consequences for
      the clinical interpretations of these measurements. No consensus has yet been
      reached on the occurrence and extent of these observations and their underlying
      processes are subject of intense scientific debate. This review will focus on
      discussing these modifications, their implications on physiology and disease and
      summarizes the complex interplays of different enzymes on the molecular forms of
      cTnT and their associated effects. 

PMID- 23871789
TI  - Formaldehyde inhalation reduces respiratory mechanics in a rat model with
      allergic lung inflammation by altering the nitric oxide/cyclooxygenase-derived
      products relationship.
AB  - Bronchial hyperresponsiveness is a hallmark of asthma and many factors modulate
      bronchoconstriction episodes. A potential correlation of formaldehyde (FA)
      inhalation and asthma has been observed; however, the exact role of FA remains
      controversial. We investigated the effects of FA inhalation on Ovalbumin (OVA)
      sensitisation using a parameter of respiratory mechanics. The involvement of
      nitric oxide (NO) and cyclooxygenase-derived products were also evaluated. The
      rats were submitted, or not, to FA inhalation (1%, 90 min/day, 3 days) and were
      OVA-sensitised and challenged 14 days later. Our data showed that previous FA
      exposure in allergic rats reduced bronchial responsiveness, respiratory
      resistance (Rrs) and elastance (Ers) to methacholine. FA exposure in allergic
      rats also increased the iNOS gene expression and reduced COX-1. L-NAME treatment
      exacerbated the bronchial hyporesponsiveness and did not modify the Ers and Rrs,
      while Indomethacin partially reversed all of the parameters studied. The L-NAME
      and Indomethacin treatments reduced leukotriene B4 levels while they increased
      thromboxane B2 and prostaglandin E2. In conclusion, FA exposure prior to OVA
      sensitisation reduces the respiratory mechanics and the interaction of NO and
      PGE2 may be representing a compensatory mechanism in order to protect the lung
      from bronchoconstriction effects.

PMID- 23871790
TI  - AICAR-dependent AMPK activation improves scar formation in the aged heart in a
      murine model of reperfused myocardial infarction.
AB  - We have demonstrated that scar formation after myocardial infarction (MI) is
      associated with an endogenous pool of CD44(pos)CD45(neg) multipotential
      mesenchymal stem cells (MSC). MSC differentiate into fibroblasts secreting
      collagen that forms a scar and mature into myofibroblasts that express alpha
      smooth muscle actin (alpha-SMA) that stabilizes the scar. In the aging mouse,
      cardiac repair after MI is associated with impaired differentiation of MSC; MSC
      derived from the aged hearts form dysfunctional fibroblasts that deposit less
      collagen in response to transforming growth factor beta-1 (TGF-beta1) and poorly
      mature into myofibroblasts. We found in vitro that the defect in myofibroblast
      maturation can be remedied by AICAR, which activates non-canonical TGF-beta
      signaling through AMP-activated protein kinase (AMPK). In the present study, we
      injected aged mice with AICAR and subjected them to 1h occlusion of the left
      anterior descending artery (LAD) and then reperfusion for up to 30days. AICAR
      dependent AMPK signaling led to mobilization of an endogenous CD44(pos)CD45(neg)
      MSC and its differentiation towards fibroblasts and myofibroblasts in the
      infarct. This was accompanied by enhanced collagen deposition and collagen fiber
      maturation in the scar. The AICAR-treated group has demonstrated reduced adverse
      remodeling as indicated by improved apical end diastolic dimension but no changes
      in ejection fraction and cardiac output were observed. We concluded that these
      data indicate the novel, previously not described role of AMPK in the post-MI
      scar formation. These findings can potentially lead to a new therapeutic strategy
      for prevention of adverse remodeling in the aging heart. 

PMID- 23871792
TI  - Pre-pubertal castration improves spatial learning during mid-adolescence in rats.
AB  - Hippocampus functions, including spatial cognition and stress responses, mature
      during adolescence. In addition, hippocampus neuronal structures are modified by
      circulating sex steroids, which dramatically increase during adolescence.
      Therefore, the effects of castration and the circulating levels of the main sex
      steroid testosterone on spatial learning and memory were examined across
      postnatal ages to test whether pre-pubertal castration affected rats' spatial
      ability in the Morris Water maze (MWM). Male rats were either castrated or sham
      castrated at 22d (days of age), or left gonadally intact. They were then trained
      and tested in the MWM beginning at 28d, 35d, 45d or 60d. We found that all of the
      intact rats learned the spatial task; however, the males at 22d and 28d required
      more trials to acquire the task than the males at older ages. The males castrated
      at 22d and tested at 35d had significantly lower escape latency and traveled
      distance during training than the sham-castrated males trained at the same age.
      No differences were observed in mean values of escape latency and traveled
      distance at 45d even though they had comparable levels of testosterone. We
      conclude that adult-typical performance for male spatial memory emerges during
      mid-adolescence and that pre-pubertal castration appears to improve spatial
      learning during this time. 

PMID- 23871793
TI  - Shaping dendrites with machinery borrowed from epithelia.
AB  - The ciliated receptive endings of sensory cells and the dendrites of other
      neurons are shaped by adhesive interactions, many of which depend on machinery
      also present in epithelia. Sensory cells are shaped by interactions with support
      cells through adhesion junctions via the Crumbs complex, tight junction
      components such as claudins, as well as interactions with apical extracellular
      matrix composed of zona pellucida domain proteins. Neuronal dendrites are shaped
      by adhesion machinery that includes cadherins, catenins, afadin, L1CAM, CHL1,
      Sidekicks, Contactin and Caspr, many of which are shared with epithelia. This
      review highlights this shared machinery, and suggests that mechanisms of
      epithelial morphogenesis may thus provide a guide to understanding dendrite
      morphogenesis. 

PMID- 23871795
TI  - Labor patterns in twin gestations.
AB  - OBJECTIVE: To compare labor progression in twin vs singleton gestations. STUDY
      DESIGN: Retrospective review of electronic database created by Consortium on Safe
      Labor, reflecting labor and delivery information from 12 clinical centers 2002
      2008. Women with twin gestations, cephalic presentation of presenting twin,
      gestational age >=34 weeks, with >=2 cervical examinations were included.
      Exclusion criteria were fetal anomalies or demise. Singleton controls were
      selected by the same criteria. Categorical variables were analyzed by chi(2);
      continuous by Student t test. Interval censored regression was used to determine
      distribution for time of cervical dilation in centimeters, or "traverse times,"
      and controlled for confounding factors. Repeated-measures analysis constructed
      mean labor curves by parity and number of fetuses. RESULTS: A total of 891 twin
      gestations were compared with 100,513 singleton controls. Twin gestations were
      more often older, white or African American, earlier gestational age, increased
      prepregnancy body mass index, and with lower birthweight. There was no difference
      in number of prior cesarean deliveries, induction, or augmentation, or epidural
      use. Median traverse times increased at every centimeter interval in nulliparous
      twins, in both unadjusted and adjusted analysis (P < .01). A similar pattern was
      noted for multiparas in both analyses. Labor curves demonstrated a delayed
      inflection point in the labor pattern for nulliparous and multiparous twin
      gestations. CONCLUSION: Both nulliparous and multiparous women have slower
      progression of active phase labor with twins even when controlling for
      confounding factors.

PMID- 23871794
TI  - Inadequate intake of nutrients essential for neurodevelopment in children with
      fetal alcohol spectrum disorders (FASD).
AB  - This study evaluated dietary intake in children with fetal alcohol spectrum
      disorders (FASD). Pre-clinical research suggests that nutrient supplementation
      may attenuate cognitive and behavioral deficits in FASD. Currently, the dietary
      adequacy of essential nutrients in children with FASD is unknown. Dietary data
      were collected as part of a randomized, double-blind controlled trial of choline
      supplementation in FASD. Participants included 31 children with FASD, ages 2.5
      4.9 years at enrollment. Dietary intake data was collected three times during the
      nine-month study via interview-administered 24-hour recalls with the Automated
      Self-Administered 24-hour Recall. Dietary intake of macronutrients and 17
      vitamins/minerals from food was averaged across three data collection points.
      Observed nutrient intakes were compared to national dietary intake data of
      children ages 2-5 years (What we Eat in America, NHANES 2007-2008) and to the
      Dietary Reference Intakes. Compared to the dietary intakes of children in the
      NHANES sample, children with FASD had lower intakes of saturated fat, vitamin D,
      and calcium. The majority (>50%) of children with FASD did not meet the
      Recommended Dietary Allowance (RDA) or Adequate Intake (AI) for fiber, n-3 fatty
      acids, vitamin D, vitamin E, vitamin K, choline, and calcium. This pattern of
      dietary intake in children with FASD suggests that there may be opportunities to
      benefit from nutritional intervention. Supplementation with several nutrients,
      including choline, vitamin D, and n-3 fatty acids, has been shown in animal
      models to attenuate the cognitive deficits of FASD. These results highlight the
      potential of nutritional clinical trials in FASD.

PMID- 23871796
TI  - Selection bias, allocation concealment and randomization design in clinical
      trials.

PMID- 23871797
TI  - Current and future tools for global canine rabies elimination.
AB  - Even though rabies is almost uniformly fatal, it is readily preventable with
      currently available tools. Vaccination is highly efficacious for the pre-exposure
      prophylaxis (PrEP) of rabies in humans and animals, and prompt postexposure
      prophylaxis (PEP) with vaccine and rabies immune globulin (RIG) can reliably
      prevent disease in humans. However, access to these tools and knowledge of their
      proper use are often limited, especially in impoverished, rabies-enzootic
      countries with the highest disease burden. In the absence of reliable diagnostic
      capacity and risk assessments, vaccines and RIG are often administered
      inappropriately, leading to chronic supply shortages and otherwise preventable
      deaths. Rather than focusing solely on human prophylaxis, it is more cost
      effective over the long term to eliminate canine rabies in its natural
      terrestrial reservoirs. Because more than 99% of human rabies deaths result from
      dog bites, prevention efforts should focus on dogs. A versatile "One Health"
      strategy for canine rabies elimination should aim to create sustainable herd
      immunity in dogs, using proven vaccination strategies at the local level, coupled
      with community education and humane population management. Such strategies have
      succeeded in both developed and developing countries, and can be adapted to any
      locality. Numerous examples in Africa, Asia, and Latin America have shown that
      community-based, locally guided vaccination and education programs, based on a
      shared vision and long-term commitment, can eliminate canine rabies. Such
      programs should have specific goals and measurable outcomes, and should be
      conducted under the guidance of supportive governments, in collaboration with
      international partners and nongovernmental organizations. In addition to
      currently available tools, rabies prevention can be augmented by new dose-sparing
      human vaccine schedules, alternative routes of vaccine administration, monoclonal
      antibodies as an alternative to RIG, sensitive and specific point-of-care
      diagnostics and the development of canine immunocontraceptive methods. Accurate
      risk assessments of potential human exposures and support for decentralized
      laboratory capacity will be essential to ensure the most effective utilization of
      vaccines and RIG until canine rabies has been eliminated. 

PMID- 23871798
TI  - Treatment of mucosal leishmaniasis (L. infantum) with miltefosine in a patient
      with Good syndrome.
AB  - We report on a 76-year old patient with recurrent mucosal leishmaniasis. Multiple
      treatment regimens were administered. After the second relapse, immunologic
      workup and review of the patient's history revealed the presence of Good
      syndrome, characterized by immunodeficiency in patients with thymoma. The third
      relapse was treated with oral miltefosine with complete resolution of the
      lesions. Miltefosine is an option for treating Old World leishmaniasis
      (Leishmania infantum) and immunodeficiency should be considered in patients with
      recurrent leishmaniasis. 

PMID- 23871799
TI  - Technologic developments in the field of photonics for the detection of urinary
      bladder cancer.
AB  - Bladder cancer is a common cause of morbidity and mortality worldwide in an aging
      population. Each year, thousands of people, mostly men, are diagnosed with this
      disease, but many of them present too late to receive optimal treatment. As with
      all cancers, early diagnosis of bladder cancer significantly improves the
      efficacy of therapy and increases survival and recurrence-free survival rates.
      Ongoing research has identified many limitations about the sensitivity of
      standard diagnostic procedures in detecting early-stage tumors and precancerous
      changes. The consequences of this are often tumor progression and increased tumor
      burden, leading to a decrease in patient quality of life and a vast increase in
      treatment costs. The necessity for improved early detection of bladder cancer has
      spurred on research into novel methods that use a wide range of biological and
      photonic phenomena. This review will broadly discuss standard detection
      methodologies and their major limitations before covering novel photonic
      techniques for early tumor detection and staging, assessing their diagnostic
      accuracy for flat and precancerous changes. We will do so in the context of both
      cystoscopic examination and the screening of voided urine and will also touch on
      the concept of using photonic technology as a surgical tool for tumor ablation. 

PMID- 23871800
TI  - Shifting paradigms: continuous nasogastric feeding with high caloric intakes in
      anorexia nervosa.
AB  - PURPOSE: The initial goal of admission for a patient with anorexia nervosa is
      physiologic stabilization through nutritional rehabilitation balanced against the
      risk of refeeding syndrome. Recent alternative approaches emphasize meal
      composition, limiting carbohydrates, to reduce risk. The Montreal Children's
      Hospital has instituted a standardized high-calorie continuous nasogastric (NG)
      refeeding protocol for the initial management of inpatient adolescents with
      restrictive eating disorders. This study aims to confirm that this protocol
      results in a shorter admission duration and faster rate of weight gain without
      increased incidence of complications. METHODS: Retrospective chart review of
      patients with restrictive eating disorders admitted to the Montreal Children's
      Hospital during December 2003 to December 2011. Those treated with higher calorie
      NG refeeding protocol (N = 31) were compared with those managed with a standard
      bolus meal treatment (N = 134). RESULTS: Length of stay was significantly reduced
      in the NG-fed cohort (NG cohort 33.8 days; bolus-fed cohort 50.9 days; p =
      .0002). Mean rate of weight gain in the NG group was significantly improved for
      both the first and second week when compared with the bolus-fed cohort (1.22
      kg/week (1), p = .01; 1.06 kg/week (.9), p = .04). No significant difference was
      found in the rate of complications or electrolyte abnormalities with 90% of the
      NG-fed cohort receiving prophylactic phosphate supplementation from admission.
      CONCLUSIONS: This study provides further evidence to support the treatment of
      undernourished inpatients with restrictive type eating disorders with a higher
      initial caloric intake to achieve rapid and safe nutritional rehabilitation.

PMID- 23871801
TI  - Child physical and sexual abuse and cigarette smoking in adolescence and
      adulthood.
AB  - PURPOSE: Analyses used data from an extended longitudinal study to examine the
      relationship between childhood physical and sexual abuse (CPA and CSA,
      respectively) and adolescent and adult smoking behavior. Two questions guided the
      study: (1) Is there an association between childhood abuse and adolescent and
      adult smoking behavior? (2) Does the relationship between childhood abuse and
      later cigarette smoking differ for males and females? METHODS: A censored
      inflated path model was used to assess the impact of child abuse on adolescent
      and adult lifetime smoking prevalence and smoking frequency. Gender differences
      in significant model paths were assessed using a multiple-group approach.
      RESULTS: Results show no significant relation between CPA or CSA and risk of
      having ever smoked cigarettes in adolescence or adulthood. However, for males,
      both CPA and CSA had direct effects on adolescent smoking frequency. For females,
      only CSA predicted increased smoking frequency in adolescence. Adolescent smoking
      frequency predicted adult smoking frequency more strongly for females compared
      with males. CONCLUSIONS: CPA and CSA are risk factors for higher frequency of
      smoking in adolescence. Higher frequency of cigarette smoking in adolescence
      increases the risk of higher smoking frequency in adulthood. Results underscore
      the need for both primary and secondary prevention and intervention efforts to
      reduce the likelihood of childhood abuse and to lessen risk for cigarette smoking
      among those who have been abused.

PMID- 23871802
TI  - Timing and circumstances of first sex among female and male youth from select
      urban areas of Nigeria, Kenya, and Senegal.
AB  - PURPOSE: To examine the timing and circumstances of first sex among urban female
      and male youth in Kenya, Nigeria, and Senegal. METHODS: Recently collected data
      are used to examine youth sexual behaviors in Kenya, Nigeria, and Senegal. In
      each country, a large, representative sample of women (ages 15-49) and men (ages
      15-59) was collected from multiple cities. Data from youth (ages 15-24) are used
      for the analyses of age at sexual initiation, whether first sex was premarital,
      and modern family planning use at first sex. Cox proportional hazard models and
      logistic regression analyses are performed to determine factors associated with
      these outcomes. RESULTS: Across all three countries, a greater percentage of male
      youth than female youth report initiating sex with a nonmarital partner. More
      educated youth are less likely to have initiated sex at each age. In Nigeria and
      Senegal, poor female youth report earlier first sex than wealthier female youth.
      In Kenya, richer female youth are more likely to have premarital first sex and to
      use contraception/condom at first sex than their poorer counterparts. Older age
      at first sex and youth who report that first sex was premarital are significantly
      more likely to use a method of contraception (including condom) at first sex.
      City-specific distinctions are found and discussed for each outcome. CONCLUSIONS:
      Programs seeking to reduce HIV and unintended pregnancy risk among urban youth
      need to undertake needs assessments to understand the local context that
      influences the timing and circumstances of first sex in each city/country
      specific context.

PMID- 23871803
TI  - Predictors of human papillomavirus vaccination among daughters of low-income
      Latina mothers: the role of acculturation.
AB  - PURPOSE: Human papillomavirus (HPV) vaccination is a safe and effective primary
      prevention strategy for cervical cancer. Little is known about correlates of HPV
      vaccination among Hispanic adolescents living in the United States. The purpose
      of this study was to (1) examine relationships between both U.S./American and
      Latina acculturation and variables typically associated with HPV vaccine uptake
      (e.g., physician recommendation); and (2) identify predictors of HPV vaccine
      uptake among daughters of Latina mothers. METHODS: Latina mothers (N = 200)
      recruited from a Federally Qualified Health Center serving low-income families in
      Florida completed a semistructured interview that assessed awareness of and
      knowledge about HPV and HPV-vaccines, vaccination beliefs, whether their
      daughter's physician had recommended the HPV vaccine, health history,
      U.S./American and Latina acculturation, mother and daughter demographics, and
      daughter's HPV vaccination status. RESULTS: Only 18% of daughters had received at
      least one dose of the vaccine. Higher levels of U.S./American acculturation were
      associated with greater odds of vaccine uptake and other common predictors of HPV
      vaccination (e.g., physician recommendation, vaccine awareness). A multivariate
      logistic regression analysis identified three independent predictors of vaccine
      uptake: physician recommendation, daughter's age, and low worry about how to pay
      for the vaccine. CONCLUSIONS: Despite generally favorable views of HPV
      vaccination, observed rates of vaccine uptake in this sample were substantially
      lower than national estimates. Latina mothers who are more integrated into U.S.
      society may be more likely to vaccinate their daughters against HPV. Findings
      provide promising directions for future HPV vaccination interventions with
      Hispanic adolescents.

PMID- 23871804
TI  - Anti-cancer mechanisms of clinically acceptable colchicine concentrations on
      hepatocellular carcinoma.
AB  - AIMS: This study was to investigate whether the clinically acceptable colchicine
      concentrations had anti-cancer effects on hepatocellular carcinoma (HCC) and
      their anti-cancer mechanisms. MAIN METHODS: Two human HCC cell lines (HCC24/KMUH,
      HCC38/KMUH) and two human cancer-associated fibroblast (CAF) cell lines
      (F28/KMUH, F59/KMUH) were investigated by proliferative assay, microarray,
      quantitative reverse transcriptase-polymerase chain reaction, and nude mouse
      study using clinically acceptable colchicine concentrations. KEY FINDINGS: Both 2
      and 6ng/mL colchicine significantly inhibited the cellular proliferation of all
      cell lines tested (P<0.05). The anti-proliferative effects of colchicine on
      F28/KMUH, HCC24/KMUH and HCC38/KMUH cells were dose-dependent. The anti
      proliferative effects of 6ng/mL colchicine on both HCC cell lines were similar to
      the effects of 1MUg/mL epirubicin. The anti-proliferative effects of colchicine
      on HCC cells could be partially explained by dose-dependent up-regulations of 2
      anti-proliferative genes (AKAP12, TGFB2) in these cells. TGFB2 was also up
      regulated in CAFs but was not dose-dependent. Up-regulation of MX1 which can
      accelerate cell death was a common effect of 6ng/mL colchicine on both CAF cell
      lines, but 2ng/mL colchicine down-regulated MX1 in F28/KMUH cells. Nude mouse
      (BALB/c-nu) experiment showed that colchicine-treated mice
      (0.07mgcolchicine/kg/day*14days) had lower increased tumor volume ratios, slower
      tumor growth rates and larger percentages of tumor necrotic areas than control
      mice (all P<0.05). SIGNIFICANCE: Clinically acceptable colchicine concentrations
      have anti-cancer effects on HCC. This drug has potential for the palliative
      treatment of HCC.

PMID- 23871805
TI  - Beneficial effects of (RS)-glucoraphanin on the tight junction dysfunction in a
      mouse model of restraint stress.
AB  - AIMS: The purpose of this work is to evaluate the effects of (RS)-glucoraphanin,
      a glucosinolate present in Brassicaceae, notably in Tuscan black kale, and
      bioactivated with myrosinase enzyme (bioactive RS-GRA) (10mg/kg
      intraperitoneally), and to assess its capacity to prevent the dysfunction of the
      blood-brain barrier (BBB), a fundamental structure for brain homeostasis, in a
      mouse model of restraint stress. MAIN METHODS: CD1 mice were subjected to
      restraint stress by blocking the body with a tape on a table for 150 min at the
      four extremities. After the sacrifice of the animals, stomachs and brains were
      collected to perform histological evaluation, Evan's blue dye,
      immunohistochemistry and western blotting analysis, to evaluate whether
      immobilization stress leads to alterations of tight junction (TJ) components,
      such as claudin-1, claudin-3 and ZO-1. KEY FINDINGS: Immobilization causes
      considerable damage to BBB as shown by detection of Evan's blue dye, indicating a
      high level of extravasation due to stress. BBB alterations were accompanied by an
      enhancement of GFAP expression, IkB-alpha degradation followed by increased NF
      kBp65 nuclear translocation, as well as caspase 3 overexpression. Conversely, our
      results revealed that bioactive RS-GRA treatment significantly counteracts the
      changes in all these parameters and preserves TJ integrity reducing the
      production of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta, and
      increasing the production of IL-10, an anti-inflammatory cytokine. Additionally,
      bioactive RS-GRA shows antioxidant properties modulating iNOS and nitrotyrosine
      expression. SIGNIFICANCE: Our results clearly show that bioactive RS-GRA could
      represent a possible treatment during pharmacological therapy of stress.

PMID- 23871806
TI  - Medicinal plants from open-air markets in the State of Rio de Janeiro, Brazil as
      a potential source of new antimycobacterial agents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants are traditionally traded
      in open-air markets in Rio de Janeiro State (Brazil) to treat tuberculosis (TB)
      and related symptoms. AIMS OF THE STUDY: Conduct a survey in the open-air markets
      of 20 cities of Rio de Janeiro State to find medicinal plants that are popularly
      used to treat tuberculosis and other related diseases and assess their in vitro
      antimycobacterial activity. MATERIALS AND METHODS: We used direct observation and
      semi-structured interviews and asked herbalists to list species (free listing) in
      order to gather data about the plant species most commonly used for lung
      problems. We calculated a Salience Index and acquired two species of "erva-de
      passarinho" (mistletoe), Struthanthus marginatus and Struthanthus concinnus
      (Loranthaceae), commonly used to treat tuberculosis for a bioassay-guided
      isolation of the antimycobacterial active principles. Extracts, fractions and
      isolated compounds of both species were assayed in vitro against susceptible
      (H37Rv) and rifampicin-resistant (ATCC 35338) Mycobacterium tuberculosis strains.
      RESULTS: From the interviews, we generated a list of 36 plant species belonging
      to 12 families. The mistletoes Struthanthus marginatus and Struthanthus concinnus
      showed high Salience Index values among plants used to treat tuberculosis.
      Bioassay-guided fractionation of hexane extracts from both species led to the
      isolation and/or identification of steroids and terpenoids. The Minimum
      Inhibitory Concentration (MIC) of the extracts and isolated compounds ranged from
      25 to 200 MUg/mL. Some of the isolated compounds have been previously assayed
      against Mycobacterium tuberculosis, others are reported here for the first time
      (obtusifoliol: MIC H37Rv 50 MUg/mL, MIC ATCC 35338 12.5 MUg/mL; 3-O-n-acil-lup
      20(29)-en-3beta,7beta,15alpha-triol: MIC H37Rv 200 MUg/mL, MIC ATCC 35338 100
      MUg/mL). CONCLUSIONS: This study demonstrated the importance of ethnobotanical
      surveys in markets as a source for new drugs and also for scientific validation
      of folk medicine.

PMID- 23871807
TI  - Inhibitory effect of Coptis chinensis on inflammation in LPS-induced endotoxemia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma coptidis (RC) has been used as a remedy
      for inflammation-related diseases in traditional medicine. Although it is known
      to have anti-inflammatory activities, its mechanism of action on
      lipopolysaccharide (LPS)-induced inflammation has not yet been identified in
      detail. AIM OF THE STUDY: This study was designed to assess the beneficial
      effects of pretreatment with RC in ameliorating LPS-induced liver inflammation.
      MATERIALS AND METHODS: Mice were orally administered RC (500, 1000 mg/kg) for
      three days in a row. 1h after the last RC administration, the mice were
      intraperitoneally injected with LPS (35 mg/kg). After treatment, histological
      alterations and inflammatory factor levels in the liver and proinflammatory
      cytokines in the serum associated with inflammation were examined. RESULTS: We
      found that pretreatment with RC (500 and 1000 mg/kg) exerted a significant
      protective effect by attenuating liver histopathological changes in endotoxemic
      mice. The results also demonstrated that RC suppressed secretion of LPS
      stimulated pro-inflammatory cytokines, such as interleukin-6 (IL-6). Furthermore,
      RC inhibited LPS-mediated nuclear factor (NF)-kappaB activation via the
      prevention of IkappaB-alpha phosphorylation, as well as the phosphorylation of
      ERK1/2, JNK, and p38 MAPKs. These results were associated with decreases in the
      expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (I
      NOS). CONCLUSIONS: The results presented here clearly demonstrate that RC could
      significantly protect mice against LPS-induced acute liver injury.

PMID- 23871808
TI  - Neuropharmacological screening of essential oil from oleo gum resin of Gardenia
      lucida Roxb.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The oleo gum resin of Gardenia lucida is commonly
      employed in traditional medicine to treat multiple ailments, including epilepsy
      and mania. The essential oil isolated from it was screened for CNS activities to
      check if it is responsible for the claims made regarding the traditional use of
      the oleo gum resin. MATERIALS AND METHODS: The hypnotic and anticonvulsant
      activity was assessed by pentobarbitone induced hypnosis and convulsant models
      Maximum electroshock (MES) and Pentylene tetrazole (PTZ) respectively. Effect on
      motor activity was evaluated using an actophotometer, rotarod and grip strength
      methods. RESULTS: The oil significantly potentiated the barbitone induced
      hypnosis and offered significant protection against the intensity and frequency
      of convulsions and mortality rate in both the convulsant models. A significant
      decrease in locomotion, motor impairment and loss of gripping reflex was also
      observed. CONCLUSION: The essential oil of the oleo gum resin of Gardenia lucida
      is a CNS depressant and anticonvulsant with central muscle relaxant properties.
      This justifies the claims made regarding the use of the oleo gum resin of
      Gardenia lucida in CNS disorders.

PMID- 23871809
TI  - Anti-inflammatory and antinociceptive effects of hydroalcoholic extract from
      Pseudobombax marginatum inner bark from caatinga potiguar.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Pseudobombax marginatum (St Hil) Rob.,
      Malvaceae, is mentioned in ethnobotanical studies. It is used as anti
      inflammatory, for ulcers and gastritis, and back pain. To evaluate anti
      inflammatory and antinociceptive activities a hydroalcoholic extract (HE) from
      inner bark was prepared. MATERIALS AND METHODS: For the anti-inflammatory
      activity, carrageenan-induced paw edema and peritonitis models, and also
      myeloperoxidase assay were used. For the antinociceptiva activity acetic acid
      induced writhing, hot plate and formalin tests were employed. RESULTS: The HE
      extract exhibited an intense inhibition in carrageenan-induced edema model and
      also in myeloperoxidase activity at the doses of 100 and 300 mg/kg. The leukocyte
      migration into the peritoneal cavity was also inhibited at the doses of 30, 100
      and 300 mg/kg. A similar profile was observed against acid-induced abdominal
      contortions and in formalin second phase test at the doses of 30 and 100 mg/kg,
      but this treatment did not affect the behavior of animals in the hot plate test.
      CONCLUSIONS: The experimental data of the HE from Pseudobombax marginatum show
      anti-inflammatory and antinociceptiva activities, confirming the indication from
      traditional medicine; however further studies are required to define and isolate
      the active anti-inflammatory and antinociceptiva components from this active
      specie.

PMID- 23871810
TI  - Enhancing microsurgical skills through deliberate practice.

PMID- 23871811
TI  - 3D printing and neurosurgery--ready for prime time?

PMID- 23871812
TI  - Atypical meningioma: a study of prognostic factors.
AB  - OBJECTIVE: Atypical meningiomas represent 20% of all meningiomas. This
      retrospective study analyzes the prognostic factors, the effect of different
      methods of treatments, and the behavior of atypical meningiomas. METHODS: The
      study comprised 44 patients who were given a diagnosis of atypical meningioma
      according to the 2007 World Health Organization classification in the period from
      January 2009 to March 2012. Data collected included patient age, gender, tumor
      location, presenting symptoms, and treatment received. Patients were followed to
      detect recurrence and assess survival. RESULTS: Median overall survival was 57
      months, with a 5-year survival of 35%. Significantly better survival was observed
      for patients <50 years old (65 months vs. 46 months, P = 0.033) and patients with
      total resection (Simpson grade 1-2) compared with subtotal resection (Simpson
      grade 3-4) or biopsy (Simpson grade 5) (75 months vs. 46 months and 24 months, P
      < 0.0001). Patients with a tumor located in brain convexity had better survival
      but with no statistical significance (P = 0.052). Multivariate analysis showed
      prognostic significance with age (P = 0.030) and extent of resection (P < 0.000).
      Progression-free survival ranged from 7-83 months with a median of 39 months.
      Progression-free survival showed a significant relationship with subtotal
      resection compared with biopsy (P = 0.007). Recurrences were less in patients who
      received radiotherapy (RT), and this was statistically significant (P = 0.007).
      CONCLUSIONS: Long-term survival is possible for patients with atypical
      meningiomas treated with surgery and postoperative RT. Multivariate analysis
      confirmed that age (<50 years) and total surgical excision were independent
      prognostic factors for survival. Adjuvant RT reduces tumor recurrence, especially
      after incomplete surgery.

PMID- 23871813
TI  - Endoscopic-assisted visualization of 5-aminolevulinic acid-induced fluorescence
      in malignant glioma surgery: a technical note.
AB  - OBJECTIVE: With the use of fluorescence-guided resection with 5-aminolevulinic
      acid (5-ALA), the rate of complete resection of the contrast-enhancing part of
      malignant gliomas could be increased from 36% to 65%. Because the visualization
      of 5-ALA-induced fluorescence depends on a sufficient exposure to fluorescent
      light, residual tumor tissue in deep-seated resection cavities might not be
      detected. In addition, subcortical parts of a large spherical tumor might not be
      visualized, owing to a tangential position at the periphery of the microscopic
      field. With the availability of a specially designed endoscope with the
      capability to visualize 5-ALA fluorescence, we investigated the impact of this
      new technique on the visualization of residual glioma tissue. METHODS: A standard
      dose of 5-ALA 20 mg/kg was administered to 9 patients with deep-seated contrast
      enhancing brain tumors 3 hours before surgery. A standard surgical exposure was
      performed and supplemented by the use of a specially designed endoscope with an
      option of 5-ALA fluorescence guidance. After microscopic visualization of the
      surgical cavity, endoscopic visualization was employed. If additional
      fluorescence tissue was detected, microscopic visualization was performed.
      Detected remnants of the tumor were removed and evaluated by histologic
      examination. RESULTS: In all cases, fluorescence-guided endoscopic visualization
      identified 5-ALA-positive tissue not sufficiently exposed by conventional
      microscopic visualization. In 8 patients, histopathologic examination confirmed
      residual tumor tissue; in 1 patient, the endoscopic visualized tissue was
      classified as radiation necrosis. In this patient, the tumor was completely ALA
      negative microscopically. CONCLUSIONS: As an additional instrument, fluorescence
      guided endoscopic visualization might help to overcome technical limitations of
      the conventional microscopic exposure of 5-ALA-positive tumor tissue. The false
      positive 5-ALA tissue indicates that endoscopic visualization may overestimate
      the amount of tumor, so further analyses to ascertain the sensitivity and
      specificity of this technique are required.

PMID- 23871814
TI  - Treatment of intracranial aneurysms with the pipeline embolization device from a
      U.S. multicenter experience.

PMID- 23871815
TI  - The future of intracranial aneurysm management: personalized medicine.

PMID- 23871816
TI  - Teaching and sustainably implementing awake craniotomy in resource-poor settings.
AB  - OBJECTIVE: Awake craniotomy for brain tumor resection has the benefit of avoiding
      a general anesthetic and decreasing associated costs (e.g., intensive care unit
      beds and intravenous line insertion). In low- and middle-income countries,
      significant resource limitations for the system and individual make awake
      craniotomy an ideal tool, yet it is infrequently used. We sought to determine if
      awake craniotomy could be effectively taught and implemented safely and
      sustainably in low- and middle-income countries. METHODS: A neurosurgeon
      experienced in the procedure taught awake craniotomy to colleagues in China,
      Indonesia, Ghana, and Nigeria during the period 2007-2012. Patients were selected
      on the basis of suspected intraaxial tumor, absence of major dysphasia or
      confusion, and ability to tolerate the positioning. Data were recorded by the
      local surgeons and included preoperative imaging, length of hospital admission,
      final pathology, postoperative morbidity, and mortality. RESULTS: Awake
      craniotomy was performed for 38 cases of suspected brain tumor; most procedures
      were completed independently. All patients underwent preoperative computed
      tomography or magnetic resonance imaging. In 64% of cases, patients remained in
      the hospital <10 days. The most common pathology was high-grade glioma, followed
      by meningioma, low-grade glioma, and metastasis. No deaths occurred, and no case
      required urgent intubation. The most common perioperative and postoperative issue
      was seizure, with 1 case of permanent postoperative deficit. CONCLUSIONS: Awake
      craniotomy was successfully taught and implemented in 6 neurosurgical centers in
      China, Indonesia, Ghana, and Nigeria. Awake craniotomy is safe, resource-sparing,
      and sustainable. The data suggest awake craniotomy has the potential to
      significantly improve access to neurosurgical care in resource-challenged
      settings.

PMID- 23871817
TI  - Impact of activated carbon, biochar and compost on the desorption and
      mineralization of phenanthrene in soil.
AB  - Sorption of PAHs to carbonaceous soil amendments reduces their dissolved
      concentrations, limiting toxicity but also potentially biodegradation. Therefore,
      the maximum abiotic desorption of freshly sorbed phenanthrene (<=5 mg kg(-1)) was
      measured in three soils amended with activated carbon (AC), biochar or compost.
      Total amounts of phenanthrene desorbed were similar between the different soils,
      but the amendment type had a large influence. Complete desorption was observed in
      the unamended and compost amended soils, but this reduced for biochar (41%
      desorbed) and AC (8% desorbed). Cumulative amounts mineralized were 28% for the
      unamended control, 19% for compost, 13% for biochar and 4% for AC. Therefore, the
      effects of the amendments in soil in reducing desorption were also reflected in
      the extents of mineralization. Modeling was used to analyze key processes,
      indicating that for the AC and charcoal treatments bacterial activity did not
      limit mineralization, but rather desorption into the dissolved phase.

PMID- 23871818
TI  - Variations in exposure to traffic pollution while travelling by different modes
      in a low density, less congested city.
AB  - This research assessed the comparative risk associated with exposure to traffic
      pollution when travelling via different transport modes in Christchurch, New
      Zealand. Concentrations of PM1, UFPs and CO were monitored on pre-defined routes
      during the morning and evening commute on people travelling concurrently by car,
      bus and bicycle. It was found that car drivers were consistently exposed to the
      highest levels of CO; on-road cyclists were exposed to higher levels of all
      pollutants than off-road cyclists; car and bus occupants were exposed to higher
      average levels of UFP than cyclists, and travellers were occasionally exposed to
      very high levels of pollution for short periods of time. PM10 and PM2.5 were
      found to be poor indicators of exposure to traffic pollution. Studying
      Christchurch adds to our understanding as it was a lower density city with
      limited traffic congestion compared most other cities previously studied.

PMID- 23871819
TI  - Chlorinated pesticides in stream sediments from organic, integrated and
      conventional farms.
AB  - To determine if current sheep/beef farming practices affect pesticide residues in
      streams, current-use and legacy chlorinated pesticides were quantified in 100
      sediment samples from 15 streams on the South Island of New Zealand. The study
      involved five blocks of three neighboring farms, with each block containing farms
      managed by organic, integrated and conventional farming practices. Significantly
      higher concentrations of dieldrin, ? endosulfans, ? current-use pesticides, and ?
      chlorinated pesticides were measured in sediments from conventional farms
      compared to organic and integrated farms. However, streams in the latter two
      farming categories were not pesticide-free and sometimes contained relatively
      high concentrations of legacy pesticides. Comparison of measured pesticide
      concentrations with sediment quality guidelines showed that, regardless of
      farming practice, mean pesticide concentrations were below the recommended
      toxicity thresholds. However, up to 23% of individual samples contained
      chlorpyrifos, endosulfan sulfate, ? DDT, dieldrin, or ? chlordane concentrations
      above these thresholds.

PMID- 23871820
TI  - Similarity-based virtual screening for microtubule stabilizers reveals novel
      antimitotic scaffold.
AB  - Microtubules are among the most studied and best characterized cancer targets
      identified to date. Many microtubule stabilizers have been introduced so far that
      work by disrupting the dynamic instability of microtubules causing mitotic block
      and apoptosis. However, most of these molecules, especially taxol and epothilone,
      suffer absorption, toxicity and/or resistance problems. Here we employ a novel
      similarity-based virtual screening approach in the hope of finding other
      microtubule stabilizers that perform better and have lower toxicity and
      resistance. Epothilones, discodermolide, eleutherobin and sarcodictyin A have
      been found to compete with taxanes for the beta-tubulin binding site, which
      suggests common chemical features qualifying for that. Our approach was based on
      similarity screening against all these compounds and other microtubule
      stabilizers, followed by virtual screening against the taxol binding site. Some
      novel hits were found, together with a novel highly rigid molecular scaffold.
      After visual manipulations, redocking and rescoring of this novel scaffold, its
      affinity dramatically increased in a promising trend, which qualifies for
      biological testing. 

PMID- 23871821
TI  - Getting to the guts of the matter: the status and potential of 'omics' research
      of parasitic protists of the human gastrointestinal system.
AB  - Parasitic protists are a major cause of diarrhoeal illnesses in humans globally.
      Collectively, enteric pathogens exceed all other forms of infectious disease, in
      terms of their estimated global prevalence and socioeconomic impact. They have a
      disproportionately high impact on children in impoverished communities, leading
      to acute (diarrhoea, vomiting, dehydration and death) and chronic disease
      (malabsorption, malnutrition, physical and cognitive stunting and predisposition
      to chronic, non-communicable disease) consequences. However, historically,
      investment in research and disease control measures has been disproportionately
      poor, leading to their current classification as neglected pathogens. A sound
      understanding of their biology is essential in underpinning detection, treatment
      and control efforts. One major tool in rapidly improving our knowledge of these
      parasites is the use of biological systems, including 'omic' technologies. In
      recent years, these tools have shown significant success when applied to enteric
      protists. This review summarises much of this knowledge and highlights the
      significant remaining knowledge gaps. A major focus of the present review was to
      provide a perspective on a way forward to address these gaps using advanced
      biotechnologies. 

PMID- 23871822
TI  - Concomitant administration of GonaConTM and rabies vaccine in female dogs (Canis
      familiaris) in Mexico.
AB  - Mexico serves as a global model for advances in rabies prevention and control in
      dogs. The Mexican Ministry of Health (MMH) annual application of approximately 16
      million doses of parenteral rabies vaccine has resulted in significant reductions
      in canine rabies during the past 20 years. One collateral parameter of rabies
      programs is dog population management. Enhanced public awareness is critical to
      reinforce responsible pet ownership. Surgical spaying and neutering remain
      important to prevent reproduction, but are impractical for achieving dog
      population management goals. GonaConTM, an anti-gonadotropin releasing hormone
      (GnRH) vaccine, was initially tested in captive female dogs on the Navajo Nation,
      2008. The MMH led this international collaborative study on an improved
      formulation of GonaConTM in captive dogs with local representatives in Hidalgo,
      Mexico in 2011. This study contained 20 bitches assigned to Group A (6 control),
      Group B (7 GonaConTM), and Group C (7 GonaConTM and rabies vaccine). Vaccines
      were delivered IM. Animals were placed under observation and evaluated during the
      61-day trial. Clinically, all dogs behaved normally. No limping or prostration
      was observed, in spite of minor muscle atrophy post-mortem in the left hind leg
      of dogs that received GonaConTM. Two dogs that began the study pregnant give
      birth to healthy pups. Dogs that received a GonaConTM injection had macro and
      microscopic lesions consistent with prior findings, but the adverse injection
      effects were less frequent and lower in intensity. Both vaccines were immunogenic
      based on significant increases in rabies virus neutralizing antibodies and anti
      GnRH antibodies in treatment Groups B and C. Simultaneous administration of
      GonaConTM and rabies vaccine in Group C did not affect immunogenicity.
      Progesterone was suppressed significantly in comparison to controls. Future
      studies that monitor fertility through multiple breeding cycles represent a
      research need to determine the value of integrating this vaccine into dog rabies
      management. 

PMID- 23871823
TI  - Validity of a reported history of chickenpox in targeting varicella vaccination
      at susceptible adolescents in England.
AB  - INTRODUCTION: In the UK, primary varicella is usually a mild infection in
      children, but can cause serious illness in susceptible pregnant women and adults.
      The UK Joint Committee on Vaccination and Immunisation is considering an
      adolescent varicella vaccination programme. Cost-effectiveness depends upon
      identifying susceptibles and minimising vaccine wastage, and chickenpox history
      is one method to screen for eligibility. To inform this approach, we estimated
      the proportion of adolescents with varicella antibodies by reported chickenpox
      history. METHODS: Recruitment occurred through secondary schools in England from
      February to September 2012. Parents were asked about their child's history of
      chickenpox, explicitly setting the context in terms of the implications for
      vaccination. 247 adolescents, whose parents reported positive (120), negative
      (77) or uncertain (50) chickenpox history provided oral fluid for varicella
      zoster virus-specific immunoglobulin-G (VZV-IgG) testing. RESULTS: 109 (90.8%
      [85.6-96.0%]) adolescents with a positive chickenpox history, 52 (67.5% [57.0
      78.1%]) with a negative history and 42 (84.0% [73.7-94.3%]) with an uncertain
      history had VZV-IgG suggesting prior infection. Combining negative and uncertain
      histories, 74% had VZV-IgG (best-case). When discounting low total-IgG samples
      and counting equivocals as positive (worst-case), 84% had VZV-IgG. We also
      modelled outcomes by varying the negative predictive value (NPV) for the antibody
      assay, and found 74-87% under the best-case and 84-92% under the worst-case
      scenario would receive vaccine unnecessarily as NPV falls to 50%. CONCLUSION:
      Reported chickenpox history discriminates between varicella immunity and
      susceptibility in adolescents, but significant vaccine wastage would occur if
      this approach alone were used to determine vaccine eligibility. A small but
      important proportion of those with positive chickenpox history would remain
      susceptible. These data are needed to determine whether reported history, with or
      without oral fluid testing in those with negative and uncertain history, is
      sufficiently discriminatory to underpin a cost-effective adolescent varicella
      vaccination programme.

PMID- 23871824
TI  - Public finance of rotavirus vaccination in India and Ethiopia: an extended cost
      effectiveness analysis.
AB  - BACKGROUND: An estimated 4% of global child deaths (approximately 300,000 deaths)
      were attributed to rotavirus in 2010. About a third of these deaths occurred in
      India and Ethiopia. Public finance of rotavirus vaccination in these two
      countries could substantially decrease child mortality and also reduce rotavirus
      related hospitalizations, prevent health-related impoverishment and bring
      significant cost savings to households. METHODS: We use a methodology of
      'extended cost-effectiveness analysis' (ECEA) to evaluate a hypothetical publicly
      financed program for rotavirus vaccination in India and Ethiopia. We measure
      program impact along four dimensions: 1) rotavirus deaths averted; 2) household
      expenditures averted; 3) financial risk protection afforded; 4) distributional
      consequences across the wealth strata of the country populations. RESULTS: In
      India and Ethiopia, the program would lead to a substantial decrease in rotavirus
      deaths, mainly among the poorer; it would reduce household expenditures across
      all income groups and it would effectively provide financial risk protection,
      mostly concentrated among the poorest. Potential indirect benefits of vaccination
      (herd immunity) would increase program benefits among all income groups, whereas
      potentially decreased vaccine efficacy among poorer households would reduce the
      equity benefits of the program. CONCLUSIONS: Our approach incorporates financial
      risk protection and distributional consequences into the systematic economic
      evaluation of vaccine policy, illustrated here with the case study of public
      finance for rotavirus vaccination. This enables selection of vaccine packages
      based on the quantitative inclusion of information on equity and on how much
      financial risk protection is being bought per dollar expenditure on vaccine
      policy, in addition to how much health is being bought.

PMID- 23871825
TI  - Alzheimer's disease treated patients showed different patterns for oxidative
      stress and inflammation markers.
AB  - Alzheimer's disease (AD) is the most common type of dementia accounting for 60
      80% of the reported cases. The aim of this study was to evaluate levels of
      certain parameters of oxidative stress and markers of endothelial dysfunction in
      the blood of 21 AD patients under standard treatment compared with 10 controls,
      in an attempt to elucidate the contribution of AD to the total oxidative stress
      status of the patients. Results indicate that IL-6, TNF-alpha, ADMA and
      homocysteine levels were significantly elevated in AD patients. Protein carbonyls
      levels were higher in AD group, while glutathione reductase and total antioxidant
      capacity were lower, depicting decreased defense ability against reactive oxygen
      species. Besides, a higher level of advanced glycation end-products was observed
      in AD patients. Depending on the treatment received, a distinct inflammatory and
      oxidative stress profile was observed: in Rivastigmine-treated group, IL6 levels
      were 47% lower than the average value of the remaining AD patients; homocysteine
      and glutathione reductase were statistically unchanged in the Rivastigmine and
      Donepezil-Memantine, respectively Donepezil group. Although the study is based on
      a limited population, the results could constitute the basis for further studies
      regarding the effect of medication and diet on AD patients. 

PMID- 23871826
TI  - Dioscin, a natural steroid saponin, induces apoptosis and DNA damage through
      reactive oxygen species: a potential new drug for treatment of glioblastoma
      multiforme.
AB  - Dioscin, a natural product obtained from medicinal plants shows lipid-lowering,
      anti-cancer and hepatoprotective effects. However, the effect of it on
      glioblastoma is unclear. In this study, dioscin significantly inhibited
      proliferation of C6 glioma cells and caused reactive oxygen species (ROS)
      generation and Ca2+ release. ROS accumulation affected levels of malondialdehyde,
      nitric oxide, glutathione disulfide and glutathione, and caused cell apoptosis.
      In addition, ROS generation caused mitochondrial damage including structural
      changes, increased mitochondrial permeability transition and decreased
      mitochondria membrane potential, which led to the release of cytochrome C,
      nuclear translation of programmed cell death-5 and increased activities of
      caspase-3,9. Simultaneously, dioscin down-regulated protein expression of Bcl-2,
      Bcl-xl, up-regulated expression of Bak, Bax, Bid and cleaved poly (ADP-ribose)
      polymerase. Also, oxygen stress induced S-phase arrest of cancer cells by way of
      regulating expression of DNA Topo I, p53, CDK2 and Cyclin A and caused DNA
      damage. In a rat allograft model, dioscin significantly inhibited tumor size and
      extended the life cycle of the rats. In conclusion, dioscin shows noteworthy anti
      cancer activity on glioblastoma cells by promoting ROS accumulation, inducing DNA
      damage and activating mitochondrial signal pathways. Ultimately, we believe
      dioscin has promise as a new therapy for the treatment of glioblastoma.

PMID- 23871827
TI  - Protective effect of extract of Crataegus pinnatifida pollen on DNA damage
      response to oxidative stress.
AB  - The protective effect of extract of Crataegus pinnatifida (Rosaceae) pollen
      (ECPP) on the DNA damage response to oxidative stress was investigated and
      assessed with an alkaline single-cell gel electrophoresis (SCGE) assay and pBR322
      plasmid DNA breaks in site-specific and non-site-specific systems. Total phenolic
      content, total flavonoid content, individual phenolic compounds, antioxidant
      activities (1,1-diphenyl-2-picrylhydrazyl (DPPH), radical scavenging activity,
      FRAP, and chelating activity) were also determined. The results showed that ECPP
      possessed a strong ability to protect DNA from being damaged by hydroxyl radicals
      in both the site-specific system and the non-site-specific system. It also
      exhibited a cytoprotection effect in mouse lymphocytes against H2O2-induced DNA
      damage. These protective effects may be related to its high total phenolic
      content (17.65+/-0.97 mg GAE/g), total flavonoid content (8.04+/-0.97 mg
      rutin/g), strong free radical scavenging activity and considerable ferrous ion
      chelating ability (14.48+/-0.21 mg Na2EDTA/g).

PMID- 23871828
TI  - Skin tumorigenic potential of benzanthrone: prevention by ascorbic acid.
AB  - Benzanthrone (BA) exposed occupational workers have been found to exhibit
      toxicological manifestations in the skin, thus it is quite likely that long term
      exposure may lead to skin tumorigenicity. Thus, attempts were made to elucidate
      the tumor initiating and promoting potentials of pure (PBA) and commercial
      benzanthrone (CBA). Additionally, the preventive role of ascorbic acid (AsA) was
      also assessed. PBA showed tumor initiating activity while CBA demonstrated tumor
      initiating as well as promoting activities in two-stage mouse skin tumor
      protocol. Further, prior treatment of AsA to PBA and CBA followed by twice weekly
      application of 12-o-tetradecanoyl phorbal myristate acetate (TPA) resulted into
      delayed onset of tumor formation and similarly single application of 7,12
      dimethylbenz [alpha] anthracene (DMBA) followed by twice weekly application of
      AsA and CBA showed an increase in the latency period. Thus, AsA showed a
      protective effect against CBA promoted skin tumor. Furthermore, the topical
      application of CBA significantly increased the levels of xenobiotic enzymes. The
      animals topically treated with AsA along with topical application of CBA,
      restored all the impairment observed in enzyme activities. Thus, this study
      suggested that AsA can be useful in preventing PBA and CBA induced skin
      tumorigenicity. 

PMID- 23871829
TI  - Octaphlorethol A, a novel phenolic compound isolated from Ishige foliacea,
      protects against streptozotocin-induced pancreatic beta cell damage by reducing
      oxidative stress and apoptosis.
AB  - Pancreatic beta cells are extremely sensitive to oxidative stress, which probably
      has an important role in beta cell damage in diabetes. The protective effect of
      octaphlorethol A (OPA), a novel phenolic compound isolated from Ishige foliacea,
      against streptozotocin (STZ)-induced pancreatic beta cell damage was investigated
      using a rat insulinoma cell line (RINm5F pancreatic beta cells). Pretreatment
      with OPA decreased the death of STZ-treated pancreatic beta cells at
      concentrations of 12.5 MUg/ml or 50 MUg/ml, and reduced the generation of
      thiobarbituric acid reactive substances and intracellular reactive oxygen species
      in a dose-dependent manner in STZ-treated pancreatic beta cells. In addition, the
      OPA pretreatment increased the activities of antioxidant enzymes such as
      catalase, superoxide dismutase, and glutathione peroxidase in STZ-treated
      pancreatic beta cells. Moreover, OPA treatment elevated the level of insulin,
      which was reduced by STZ treatment, and protected pancreatic beta cells against
      damage under STZ-treated conditions. These effects were mediated by suppressing
      apoptosis and were associated with increased anti-apoptotic Bcl-xL expression and
      reduced pro-apoptotic Bax and cleaved caspase-3 expression. These findings
      indicate that OPA may be useful as a potential pharmaceutical agent to protect
      against pancreatic beta cell damage caused by oxidative stress associated with
      diabetes.

PMID- 23871832
TI  - The small GTPase N-Ras regulates extracellular matrix synthesis, proliferation
      and migration in fibroblasts.
AB  - In addition to their role as oncogenes, Ras GTPases are key regulators of cell
      function. There is a proven relationship between the signaling pathways of
      transforming growth factor-beta1 (TGF- beta1) and Ras GTPases. Each of the Ras
      isoforms (H, N and K) exhibits specific modulatory activity on different cellular
      pathways. Our purpose has been to study some of the mechanisms involved in the
      development of renal fibrosis, assessing the individual role of N-Ras in basal
      and TGF-beta1-mediated extracellular matrix (ECM) synthesis, proliferation, and
      migration in immortalized N-Ras deficient fibroblasts (N-ras(-/-)). Compared to
      normal counterparts, fibroblasts deficient for N-Ras exhibited higher basal
      activity levels of phosphatidylinositol-3-kinase (PI3K)/Akt and MEK/Erk,
      accompanied by upregulated collagen synthesis and diminished proliferation and
      migration rates. We found that the absence of N-Ras did not affect TGF-beta1
      induced proliferation and migration, which required PI3K/Akt but not Erk1/2
      activation. Similar effector pathway dependence was found for fibronectin and
      collagen type I expression. Our results indicate that N-Ras might contribute to
      renal fibrosis through the down-regulation of ECM synthesis and up-regulation
      proliferation and migration modulating Akt activation. N-Ras also regulates TGF
      beta1-induced collagen I and fibronectin expression through Erk-independent
      pathways. 

PMID- 23871831
TI  - A new mechanism of RhoA ubiquitination and degradation: roles of SCF(FBXL19) E3
      ligase and Erk2.
AB  - RhoA is a small GTPase multifunctional protein that regulates cell proliferation
      and cytoskeletal reorganization. Regulation of its protein stability plays an
      important role in its biological functions. We have shown that a Skp1-Cul1-F-box
      (SCF) FBXL19 E3 ubiquitin ligase targets Rac1, a related member of the Rho family
      for ubiquitination and degradation. Here, SCF(FBXL19) mediates RhoA
      ubiquitination and proteasomal degradation in lung epithelial cells. Ectopically
      expressed FBXL19 decreased RhoA wild type, active, and inactive forms. Cellular
      depletion of FBXL19 increased RhoA protein levels and extended its half-life.
      FBXL19 bound the small GTPase in the cytoplasm leading to RhoA ubiquitination at
      Lys(135). A RhoA(K135R) mutant protein was resistant to SCF(FBXL19)-mediated
      ubiquitination and degradation and exhibited a longer lifespan. Protein kinase
      Erk2-mediated phosphorylation of RhoA was both sufficient and required for
      SCF(FBXL19)-mediated RhoA ubiquitination and degradation. Thus, SCF(FBXL19)
      targets RhoA for its disposal, a process regulated by Erk2. Ectopically expressed
      FBXL19 reduced phosphorylation of p27 and cell proliferation, a process mediated
      by RhoA. Further, FBXL19 cellular expression diminished lysophosphatidic acid
      (LPA)-induced phosphorylation of myosin light chain (MLC) and stress fiber
      formation. Hence, SCF(FBXL19) functions as a RhoA antagonist during cell
      proliferation and cytoskeleton rearrangement. These results provide the first
      evidence of an F-box protein targeting RhoA thereby modulating its cellular
      lifespan that impacts cell proliferation and cytoskeleton rearrangement. 

PMID- 23871830
TI  - Specificity protein 4 functionally regulates the transcription of NMDA receptor
      subunits GluN1, GluN2A, and GluN2B.
AB  - N-Methyl-d-aspartate (NMDA) receptors are major glutamatergic receptors involved
      in most excitatory neurotransmission in the brain. The transcriptional regulation
      of NMDA receptors is not fully understood. Previously, we found that the GluN1
      and GluN2B subunits of the NMDA receptor are regulated by nuclear respiratory
      factors 1 and 2 (NRF-1 and NRF-2). NRF-1 and NRF-2 also regulate all 13 subunits
      of cytochrome c oxidase (COX), a critical energy-generating enzyme, thereby
      coupling neuronal activity and energy metabolism at the transcriptional level.
      Specificity protein (Sp) is a family of transcription factors that bind to GC
      rich regions, with Sp1, Sp3, and Sp4 all binding to the same cis- motifs. Sp1 and
      Sp3 are ubiquitously expressed, whereas Sp4 expression is restricted to neurons
      and testicular cells. Recently, we found that the Sp1 factor regulates all
      subunits of COX. The goal of the present study was to test our hypothesis that
      the Sp factors also regulate specific subunits of NMDA receptors, and that they
      function with NRF-1 and NRF-2 via one of three mechanisms: complementary,
      concurrent and parallel, or a combination of complementary and
      concurrent/parallel. By means of multiple approaches we found that Sp4
      functionally regulated GluN1, GluN2A, and GluN2B, but not GluN2C. On the other
      hand, Sp1 and Sp3 did not regulate these subunits as previously thought. Our data
      suggest that Sp4 operates in a complementary and concurrent/parallel manner with
      NRF-1 and NRF-2 to mediate the tight coupling between energy metabolism and
      neuronal activity at the molecular level. 

PMID- 23871833
TI  - Altered unfolded protein response is implicated in the age-related exacerbation
      of proteinuria-induced proximal tubular cell damage.
AB  - Aging is a dominant risk factor for end-stage renal disease. We analyzed the
      mechanism involved in age-related exacerbation of proteinuria-induced proximal
      tubular cell (PTC) damage by focusing on endoplasmic reticulum-related unfolded
      protein response (UPR). After equal-degree induction of proteinuria in 24-month
      old (aged) and 3-month-old (young) mice by intraperitoneal free fatty acid-bound
      albumin overload, tubulointerstitial lesions were more severe in aged than in
      young mice. In aged PTCs, proteinuria-induced cell-adaptive UPR resulting from
      induction of the molecular chaperone BiP was significantly suppressed, whereas
      proapoptotic UPR with CHOP overexpression was enhanced. Treatment with the
      exogenous molecular chaperone tauroursodeoxycholic acid (TUDCA) ameliorated
      proteinuria-induced tubulointerstitial lesions and PTC apoptosis in aged mice.
      Among the three UPR branches, alterations in the inositol-requiring 1alpha
      (IRE1alpha) pathway, but not the activating transcription factor 6 or PERK
      pathway, were associated with impaired BiP induction in aged kidneys. Moreover,
      siRNA-mediated suppression of BiP and IRE1alpha exacerbated free fatty acid-bound
      albumin-induced apoptosis in cultured PTCs, whereas siRNA-mediated CHOP
      suppression ameliorated apoptosis. Finally, proteinuria-induced BiP induction in
      PTCs was diminished in kidney specimens from elderly patients. These results
      indicate that maladaptive UPRs are involved in proteinuria-induced
      tubulointerstitial lesions exacerbation in aged kidneys, and that supplementation
      of chaperones may be used to treat elderly patients with persistent proteinuria.
      These results should improve understanding of cell vulnerability in aged kidneys.

PMID- 23871834
TI  - The secretome of mesenchymal stem cells: potential implications for
      neuroregeneration.
AB  - Mesenchymal stem cells have shown regenerative properties in many tissues. This
      feature had originally been ascribed to their multipotency and thus their ability
      to differentiate into tissue-specific cells. However, many researchers consider
      the secretome of mesenchymal stem cells the most important player in the observed
      reparative effects of these cells. In this review, we specifically focus on the
      potential neuroregenerative effect of mesenchymal stem cells, summarize several
      possible mechanisms of neuroregeneration and list key factors mediating this
      effect. We illustrate examples of mesenchymal stem cell treatment in central
      nervous system disorders including stroke, neurodegenerative disorders (such as
      Parkinson's disease, Huntington's disease, multiple system atrophy and cerebellar
      ataxia) and inflammatory disease (such as multiple sclerosis). We specifically
      highlight studies where mesenchymal stem cells have entered clinical trials. 

PMID- 23871835
TI  - The UBE2E proteins as conjugating dispersers: extending function with extended
      extensions.

PMID- 23871836
TI  - A comparison of in vitro nucleosome positioning mapped with chicken, frog and a
      variety of yeast core histones.
AB  - Using high-throughput sequencing, we have mapped sequence-directed nucleosome
      positioning in vitro on four plasmid DNAs containing DNA fragments derived from
      the genomes of sheep, drosophila, human and yeast. Chromatins were prepared by
      reconstitution using chicken, frog and yeast core histones. We also assembled
      yeast chromatin in which histone H3 was replaced by the centromere-specific
      histone variant, Cse4. The positions occupied by recombinant frog and native
      chicken histones were found to be very similar. In contrast, nucleosomes
      containing the canonical yeast octamer or, in particular, the Cse4 octamer were
      assembled at distinct populations of locations, a property that was more apparent
      on particular genomic DNA fragments. The factors that may contribute to this
      variation in nucleosome positioning and the implications of the behavior are
      discussed. 

PMID- 23871837
TI  - The evolution of alternative biofilms in an opportunistic fungal pathogen: an
      explanation for how new signal transduction pathways may evolve.
AB  - The evolution of two types of biofilms, one pathogenic and one sexual, is unique
      for Candidaalbicans, the most pervasive fungal pathogen in humans. When in the
      predominant a/alpha configuration, cells can form a traditional biofilm made up
      of a basal layer of yeast cells and an extensive upper layer of hyphae and dense
      matrix. This a/alpha biofilm is impermeable, impenetrable and drug-resistant.
      When in the a/a or alpha/alpha configuration, white cells form a biofilm of
      similar architecture, but which is permeable, penetrable and drug-susceptible.
      The latter biofilm facilitates mating between minority opaque a/a and alpha/alpha
      cells. The two biofilms are regulated by different signal transduction pathways
      that provide clues for deducing not only how the sexual a/a or alpha/alpha
      biofilms evolved, but how the pathogenic a/alpha biofilm evolved as well. In the
      deduced evolutionary models, regulatory molecules, including components of the
      signal transduction pathways and transcription factors, are recruited from
      conserved pathways. The evolution of the alternative biofilms of C. albicans
      provides a rare glimpse into how new regulatory pathways may evolve in general. 

PMID- 23871839
TI  - Glutathione and antioxidant enzymes serve complementary roles in protecting
      activated hepatic stellate cells against hydrogen peroxide-induced cell death.
AB  - BACKGROUND: In chronic liver disease, hepatic stellate cells (HSCs) are
      activated, highly proliferative and produce excessive amounts of extracellular
      matrix, leading to liver fibrosis. Elevated levels of toxic reactive oxygen
      species (ROS) produced during chronic liver injury have been implicated in this
      activation process. Therefore, activated hepatic stellate cells need to harbor
      highly effective anti-oxidants to protect against the toxic effects of ROS. AIM:
      To investigate the protective mechanisms of activated HSCs against ROS-induced
      toxicity. METHODS: Culture-activated rat HSCs were exposed to hydrogen peroxide.
      Necrosis and apoptosis were determined by Sytox Green or acridine orange
      staining, respectively. The hydrogen peroxide detoxifying enzymes catalase and
      glutathione-peroxidase (GPx) were inhibited using 3-amino-1,2,4-triazole and
      mercaptosuccinic acid, respectively. The anti-oxidant glutathione was depleted by
      L-buthionine-sulfoximine and repleted with the GSH-analogue GSH-monoethylester
      (GSH-MEE). RESULTS: Upon activation, HSCs increase their cellular glutathione
      content and GPx expression, while MnSOD (both at mRNA and protein level) and
      catalase (at the protein level, but not at the mRNA level) decreased. Hydrogen
      peroxide did not induce cell death in activated HSCs. Glutathione depletion
      increased the sensitivity of HSCs to hydrogen peroxide, resulting in 35% and 75%
      necrotic cells at 0.2 and 1mmol/L hydrogen peroxide, respectively. The
      sensitizing effect was abolished by GSH-MEE. Inhibition of catalase or GPx
      significantly increased hydrogen peroxide-induced apoptosis, which was not
      reversed by GSH-MEE. CONCLUSION: Activated HSCs have increased ROS-detoxifying
      capacity compared to quiescent HSCs. Glutathione levels increase during HSC
      activation and protect against ROS-induced necrosis, whereas hydrogen peroxide
      detoxifying enzymes protect against apoptotic cell death.

PMID- 23871840
TI  - Probiotic Pediococcus acidilactici modulates both localised intestinal- and
      peripheral-immunity in tilapia (Oreochromis niloticus).
AB  - The application of probiotics in aquaculture has received concerted research
      efforts but the localised intestinal immunological response of fish to probiotic
      bacteria is poorly understood. Therefore, a study was conducted to evaluate the
      probiotic effect of Pediococcus acidilactici on Nile tilapia (Oreochromis
      niloticus) with specific emphasis on intestinal health and probiotic levels as
      well as system level responses such as growth performance, feed utilization and
      haemato-immunological parameters under non-challenged conditions. Fish (9.19 +/-
      0.04 g) were fed either a control diet or a P. acidilactici supplemented diet (at
      2.81 * 10(6) CFU g(-)(1)) for six weeks. At the end of the study the probiotic
      was observed to populate the intestine, accounting for ca. 3% (1.59 * 10(5) CFU
      g(-)(1)) of the cultivable intestinal bacterial load. Real-time PCR indicated
      that the probiotic treatment may potentiate the immune-responsiveness of the
      intestine as up-regulation of the gene expression of the pro-inflammatory
      cytokine TNFalpha was observed in the probiotic fed fish (P < 0.05). Light
      microscopy observations revealed elevated intraepithelial leucocyte (IEL) levels
      in the intestine of P. acidilactici fed tilapia after six weeks (P < 0.05) of
      feeding and a trend towards elevated goblet cells was also observed after six
      weeks feeding (P = 0.08). Concomitantly at week six, along with elevated IELs and
      elevated TNFalpha mRNA levels in the intestine, an increased abundance of
      circulating neutrophils and monocytes were observed in fish fed the probiotic
      supplemented diet (P < 0.05). This haemopoietic expansion of innate immune cells
      could be reflective of an elevated state of immuno-readiness. Together these
      results suggest that the probiotic has a protective action on the intestinal
      mucosal cells, stimulating the innate immune response after feeding for a period
      of six weeks. These immunological modulations did not impair growth performance
      or the remaining haematological and zootechnical parameters compared to the
      control group (P > 0.05).

PMID- 23871838
TI  - Maternal nutrition and risk of obesity in offspring: the Trojan horse of
      developmental plasticity.
AB  - Mammalian embryos have evolved to adjust their organ and tissue development in
      response to an atypical environment. This adaptation, called phenotypic
      plasticity, allows the organism to thrive in the anticipated environment in which
      the fetus will emerge. Barker and colleagues proposed that if the environment in
      which the fetus emerges differs from that in which it develops, phenotypic
      plasticity may provide an underlying mechanism for disease. Epidemiological
      studies have shown that humans born small- or large-for-gestational-age, have a
      higher likelihood of developing obesity as adults. The amount and quality of food
      that the mother consumes during gestation influences birth weight, and therefore
      susceptibility of progeny to disease in later life. Studies in experimental
      animals support these observations, and find that obesity occurs as a result of
      maternal nutrient-restriction during gestation, followed by rapid compensatory
      growth associated with ad libitum food consumption. Therefore, obesity associated
      with maternal nutritional restriction has a developmental origin. Based on this
      phenomenon, one might predict that gestational exposure to a westernized diet
      would protect against future obesity in offspring. However, evidence from
      experimental models indicates that, like maternal dietary restriction, maternal
      consumption of a westernized diet during gestation and lactation interacts with
      an adult obesogenic diet to induce further obesity. Mechanistically, restriction
      of nutrients or consumption of a high fat diet during gestation may promote
      obesity in progeny by altering hypothalamic neuropeptide production and thereby
      increasing hyperphagia in offspring. In addition to changes in food intake these
      animals may also direct energy from muscle toward storage in adipose tissue.
      Surprisingly, generational inheritance studies in rodents have further indicated
      that effects on body length, body weight, and glucose tolerance appear to be
      propagated to subsequent generations. Together, the findings discussed herein
      highlight the concept that maternal nutrition contributes to a legacy of obesity.
      Thus, ensuring adequate supplies of a complete and balanced diet during and after
      pregnancy should be a priority for public health worldwide. This article is part
      of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. 

PMID- 23871841
TI  - Acceptance and commitment group therapy for health anxiety--results from a pilot
      study.
AB  - Health anxiety (or hypochondriasis) is prevalent, may be persistent and disabling
      for the sufferers and associated with high societal costs. Acceptance and
      Commitment Therapy (ACT) is a new third-wave behavioral cognitive therapy that
      has not yet been tested in health anxiety. 34 consecutive Danish patients with
      severe health anxiety were referred from general practitioners or hospital
      departments and received a ten-session ACT group therapy. Patients were followed
      up by questionnaires for 6 months. There were significant reductions in health
      anxiety, somatic symptoms and emotional distress at 6 months compared to
      baseline: a 49% reduction in health anxiety (Whiteley-7 Index), a 47% decrease in
      emotional distress (SCL-8), and a 40% decrease in somatic symptoms (SCL-90R
      Somatization Subscale). The patients' emotional representations and perception of
      the consequences of their illness (IPQ) improved significantly, and 87% of the
      patients were very or extremely satisfied with the treatment. 

PMID- 23871842
TI  - The Seventh International Symposium on Cough: hypertussivity and allotussivity.

PMID- 23871844
TI  - Characterization of Ca(2+)/H(+) exchange in the plasma membrane of Saccharomyces
      cerevisiae.
AB  - The characteristics of the Ca(2+)/H(+) exchange were directly investigated in
      functionally inverted (inside-out) plasma membrane vesicles isolated from yeast
      using an aqueous two-phase partitioning method. Results showed that following the
      generation of an inside-acid pH gradient (fluorescence quenching), addition of
      Ca(2+) caused movement of H(+) out of the vesicles (fluorescence recovery). The
      Ca(2+)/H(+) exchange displayed saturation kinetics with respect to extravesicular
      Ca(2+) and ATP concentrations in the plasma membrane, and showed specificity for
      Ca(2+). The protonophore FCCP (carbonyl cyanide p-(trifluoromethoxy)
      phenylhydrazone), abolished the fluorescence quenching and consequently inhibited
      Ca(2+)/H(+) exchange in plasma membrane vesicles. Vanadate, which is known to
      inhibit the plasma membrane H(+)-ATPase, significantly decreased the Ca(2+)
      dependent transport of H(+) out of vesicles. When the electrical potential across
      the plasma membrane was dissipated with valinomycin and potassium, the rate of
      Ca(2+)/H(+) exchange increased compared to that of the control without
      valinomycin, indicating that the stoichiometric ratio for this exchange is
      greater than 2H(+):Ca(2+). These data suggest that Ca(2+) is transported out of
      yeast cells through a Ca(2+)/H(+) exchange system that is driven by the proton
      motive force generated by the plasma membrane H(+)-ATPase.

PMID- 23871843
TI  - Early postnatal inhibition of serotonin synthesis results in long-term reductions
      of perseverative behaviors, but not aggression, in MAO A-deficient mice.
AB  - Monoamine oxidase (MAO) A, the major enzyme catalyzing the oxidative degradation
      of serotonin (5-hydroxytryptamine, 5-HT), plays a key role in emotional
      regulation. In humans and mice, MAO-A deficiency results in high 5-HT levels,
      antisocial, aggressive, and perseverative behaviors. We previously showed that
      the elevation in brain 5-HT levels in MAO-A knockout (KO) mice is particularly
      marked during the first two weeks of postnatal life. Building on this finding, we
      hypothesized that the reduction of 5-HT levels during these early stages may lead
      to enduring attenuations of the aggression and other behavioral aberrances
      observed in MAO-A KO mice. To test this possibility, MAO-A KO mice were treated
      with daily injections of a 5-HT synthesis blocker, the tryptophan hydroxylase
      inhibitor p-chloro-phenylalanine (pCPA, 300 mg/kg/day, IP), from postnatal day 1
      through 7. As expected, this regimen significantly reduced 5-HT forebrain levels
      in MAO-A KO pups. These neurochemical changes persisted throughout adulthood, and
      resulted in significant reductions in marble-burying behavior, as well as
      increases in spontaneous alternations within a T-maze. Conversely, pCPA-treated
      MAO-A KO mice did not exhibit significant changes in anxiety-like behaviors in a
      novel open-field and elevated plus-maze; furthermore, this regimen did not modify
      their social deficits, aggressive behaviors and impairments in tactile
      sensitivity. Treatment with pCPA from postnatal day 8 through 14 elicited
      similar, yet milder, behavioral effects on marble-burying behavior. These results
      suggest that early developmental enhancements in 5-HT levels have long-term
      effects on the modulation of behavioral flexibility associated with MAO-A
      deficiency. 

PMID- 23871846
TI  - Unusual self-assembly properties of Norovirus Newbury2 virus-like particles.
AB  - In the Caliciviridae family of nonenveloped, positive-stranded RNA viruses,
      Noroviruses are major causes of human and animal gastroenteritis worldwide. The
      Norovirus T=3 icosahedral capsid is made of 180 copies of the VP1 protein, as
      exemplified in the crystal structure of the virus-like particle (VLP) of the
      human Norwalk virus (NV). It was previously shown that the ca 40-nm recombinant
      NV VLP can be disassembled and reassembled in vitro. Here we report on the
      disassembly and self-assembly properties for the related (VP1 sequence identity
      of 50%) bovine Newbury2 Norovirus (NB2) VLP. Using a panel of biophysical
      techniques, we show that while the NB2 VLP displays disassembly properties
      similar to the NV VLP, NB2-VP1 shows remarkable self-assembly properties
      heretofore unreported for NV-VP1 or any other calicivirus capsid protein. These
      properties include the capabilities of self-assembling not only into regular T=3
      capsids but also into larger VLP (up to 76 nm in diameter) and of tolerating
      substitution of the spike domain for that of a distantly related Calicivirus. In
      conditions favoring the natural, T=3 capsid, NB2-VP1 reproducibly assembles by an
      apparent two-phase process. Our results establish a robust new system with which
      to probe the dynamics of viral capsid self-assembly.

PMID- 23871845
TI  - Embryonic phenotype, beta-carotene and retinoid metabolism upon maternal
      supplementation of beta-carotene in a mouse model of severe vitamin A deficiency.
AB  - We investigated the effect of beta-carotene (bC) supplementation during pregnancy
      in a mouse model of severe vitamin A deficiency, i.e. Lrat-/-Rbp-/- dams
      maintained on a vitamin A-deficient diet during gestation. bC, a provitamin A
      carotenoid, can be enzymatically cleaved to form vitamin A for use by the
      developing embryo. We found that an acute supplementation (13.5 days post coitum,
      dpc) of bC to Lrat-/-Rbp-/- dams on a vitamin A-deficient diet activated
      transcriptional mechanisms in the developing tissues to maximize the utilization
      of bC provided to the dams. Nevertheless, these regulatory mechanisms are
      inefficient under this regimen, as the embryonic phenotype was not improved. We
      further investigated the effect of a repeated supplementation of bC during a
      crucial developmental period (6.5-9.5 dpc) on the above-mentioned mouse model.
      This treatment improved the embryonic abnormalities, as 40% of the embryos showed
      a normal phenotype. In addition, analysis of retinoic acid-responsive genes, such
      as Cyp26a1 in these embryos suggests that bC cleavage results in the production
      of retinoic acid which then can be used by the embryo. Taken together, these in
      vivo studies show that bC can be used as a source of vitamin A for severely
      vitamin A-deficient mammalian embryos.

PMID- 23871847
TI  - Assessment of regional adipose tissue depots: a DXA and CT comparison in cadavers
      of elderly persons.
AB  - OBJECTIVE: Since dual energy X-ray absorptiometry (DXA) cannot distinguish
      between different adipose tissue (AT) deposits, it remains unclear how DXA
      derived body composition variables relate to anatomical tissue (sub)compartments.
      The aim of the present study was to compare and relate regional DXA variables
      with absolute tissue masses obtained by computer tomography (CT) scanning of the
      lower limbs in elderly persons. METHODS: Eleven well-preserved white Caucasian
      adults (seven male and four female cadavers) with a median age of 79.0 years
      (ranging from 68 to 96 years) were fully scanned with DXA and CT. Separate
      densities of skin tissue, AT, muscle tissue and bone were obtained by hydrostatic
      weighing. RESULTS: The leg DXA-variables were significantly related (rho-values
      between 0.60 and 0.98, P < 0.01) to CT-derived tissue counterparts, but showed
      significant systematic differences except for subcutaneous AT mass (P = 0.773).
      After controlling for other AT depots, fat as measured by DXA (fat(DXA)) related
      only to intermuscular AT (rho = 0.82, P < 0.01) in males and to subcutaneous AT
      (rho = 0.84, P < 0.05) in females. CONCLUSION: Although significantly
      interrelated, DXA and CT variables should not be used interchangeably since they
      have different quantitative and physiological significance. Our results suggest
      that fat(DXA) represents different parts of AT depots in elderly men and women.
      Since DXA is not appropriate for assessing tissue variability cautious clinical
      interpretation is warranted.

PMID- 23871848
TI  - Dietary restriction reduces age-related degeneration of stria vascularis in the
      inner ear of the rat.
AB  - We report here beneficial effects of life-long dietary restriction on the
      progression of age-associated cochlear degeneration in female Sprague-Dawley
      rats. Thirty-month old rats on a 70% dietary restriction were compared to ad
      libitum fed age-matched rats, and three-month old adult rats. As expected, aged
      dietary restricted rats displayed about 20% higher survival rate than age-matched
      rats fed ad libitum. This difference was reflected also in the auditory system.
      In the dietary restricted group, 73% of the subjects had preserved auditory
      reflexes (Preyer), and only modest degeneration of the stria vascularis of the
      inner ear was observed. In contrast, aged ad libitum fed animals, of which only
      15% had detectable Preyer reflexes, showed a marked thinning, cellular
      degeneration and loss of cell processes in the stria vascularis. The extent of
      loss of sensory hair cells (~24%) was similar in both the aged groups, and
      neither group showed a significant reduction in the number of spiral ganglion
      neurons across adult life-span. The observations thus demonstrate that dietary
      restriction delays age-related degradation of the auditory system. The results
      provide further insights into the mechanisms of strial presbycusis. 

PMID- 23871849
TI  - Previous exposure to simulated microgravity does not exacerbate bone loss during
      subsequent exposure in the proximal tibia of adult rats.
AB  - Extended periods of inactivity cause severe bone loss and concomitant
      deterioration of the musculoskeletal system. Considerable research has been aimed
      at better understanding the mechanisms and consequences of bone loss due to
      unloading and the associated effects on strength and fracture risk. One factor
      that has not been studied extensively but is of great interest, particularly for
      human spaceflight, is how multiple or repeated exposures to unloading and
      reloading affect the skeleton. Space agencies worldwide anticipate increased
      usage of repeat-flier crewmembers, and major thrust of research has focused on
      better understanding of microgravity effects on loss of bone density at
      weightbearing skeletal sites; however there is limited data available on repeat
      microgravity exposure. The adult hindlimb unloaded (HU) rat model was used to
      determine how an initial unloading cycle will affect a subsequent exposure to
      disuse and recovery thereafter. Animals underwent 28 days of HU starting at 6
      months of age followed by 56 days of recovery, and then another 28 days of HU
      with 56 days of recovery. In vivo longitudinal pQCT was used to quantify bone
      morphological changes, and ex vivo MUCT was used to quantify trabecular
      microarchitecture and cortical shell geometry at the proximal tibia metaphysis
      (PTM). The mechanical properties of trabecular bone were examined by the reduced
      platen compression mechanical test. The hypothesis that the initial HU exposure
      will mitigate decrements in bone mass and density for the second HU exposure was
      supported as pre- to post-HU declines in total BMC, total vBMD, and cortical area
      by in vivo pQCT at the proximal tibia metaphysis were milder for the second HU
      (and not significant) compared to an age-matched single HU (3% vs. 6%, 2% vs. 6%,
      and 2% vs. 6%, respectively). In contrast, the hypothesis was not supported at
      the microarchitectural level as losses in BV/TV and Tb.Th. were similar during
      2nd HU exposure and age-matched single HU. Recovery with respect to post-HU
      values and compared to aging controls for total BMC, vBMD and cortical area were
      slower in older animals exposed to single or double HU cycles compared to
      recovery of younger animals exposed to a single HU bout. Despite milder recovery
      at the older age, there was no difference between unloaded animals and controls
      at the end of second recovery period. Therefore, the data did not support the
      hypothesis that two cycles of HU exposure with recovery would have a net negative
      effect. Mechanical properties of trabecular bone were affected more severely than
      densitometric measures (35% loss in trabecular bone ultimate stress vs. 9% loss
      in trabecular vBMD), which can be attributed most prominently to reductions in
      trabecular bone density and tissue mineral density. Together, our data
      demonstrate that initial exposure to mechanical unloading does not exacerbate
      bone loss during a subsequent unloading period and two cycles of unloading
      followed by recovery do not have a cumulative net negative effect on total bone
      mineral content and density as measured by pQCT at the proximal tibia metaphysis.

PMID- 23871850
TI  - Risk factors for development of atypical femoral fractures in patients on long
      term oral bisphosphonate therapy.
AB  - Bisphosphonates (BPs) are the first-line therapy for osteoporosis. In recent
      years, atypical femoral fractures (AFF) have been described in patients on BPs
      therapy. However, the relationship between BPs and AFF remains to be clarified.
      We evaluated clinical and hormonal characteristics of AFF patients, in order to
      determine AFF risk factors. We studied 11 females with AFF and 58 females with
      typical femoral fractures (TFF), admitted to our Department for surgical repair
      between January 2008 and December 2011. All AFF patients received BPs therapy for
      6 to 13 yrs, whereas 36.2% (p<0.0001) of TFF patients received BPs for shorter
      period (TFF, 6.1+/-1.8 yr vs. AFF, 8.6+/-1.9 yr, p<0.0001). A higher prevalence
      of hypocalcemia was observed in AFF patients compared with TFF (p<0.02), with
      significantly (p<0.05) lower corrected calcium levels in AFF patients. By
      contrast a reduced prevalence of elevated PTH levels (p<0.05) was found in AFF
      patients. No significant difference in prevalence of vitamin D defect was
      observed between the two groups. Younger age (p<0.004), higher BMI (>30 kg/m2,
      p<0.03) and early menopausal age (p<0.05) were observed in AFF patients. At time
      of fracture, prevalence of osteopenia/osteoporosis and levels of bone turnover
      markers were significantly (p<0.01) lower in AFF compared with TFF patients. By
      multivariate analysis hypocalcemia, obesity, and younger age (<70 yr) were
      confirmed to be independent predictors of AFF; elevated PTH level was the
      predominant independent protective factor (p<0.004). In conclusion, our data
      indicate that clinical characteristics and metabolic factors may favor the
      development of AFF in BP treated patients. We identified hypocalcemia due to
      latent hypoparathyroidism as primary risk factor for AFF; age, obesity, early
      menopause, and BMD may also influence the development of AFF. An adequate
      clinical and metabolic assessment is suggested to prevent the development of AFF
      in BP treated patients.

PMID- 23871851
TI  - In vivo reference point indentation reveals positive effects of raloxifene on
      mechanical properties following 6 months of treatment in skeletally mature beagle
      dogs.
AB  - Raloxifene treatment has been shown previously to positively affect bone
      mechanical properties following 1 year of treatment in skeletally mature dogs.
      Reference point indentation (RPI) can be used for in vivo assessment of
      mechanical properties and has been shown to produce values that are highly
      correlated with properties derived from traditional mechanical testing. The goal
      of this study was to use RPI to determine if raloxifene-induced alterations in
      mechanical properties occurred after 6 months of treatment. Twelve skeletally
      mature female beagle dogs were treated for 6 months with oral doses of saline
      vehicle (VEH, 1 ml/kg/day) or a clinically relevant dose of raloxifene (RAL, 0.5
      mg/kg/day). At 6 months, all animals underwent in vivo RPI (10N force, 10 cycles)
      of the anterior tibial midshaft. RPI data were analyzed using a custom MATLAB
      program, designed to provide cycle-by-cycle data from the RPI test and validated
      against the manufacturer-provided software. Indentation distance increase (IDI),
      a parameter that is inversely related to bone toughness, was significantly lower
      in RAL-treated animals compared to VEH (-16.5%), suggesting increased bone
      toughness. Energy absorption within the first cycle was significantly lower with
      RAL compared to VEH (-21%). These data build on previous work that has documented
      positive effects of raloxifene on material properties by showing that these
      changes exist after 6 months.

PMID- 23871852
TI  - Improvements in hip trabecular, subcortical, and cortical density and mass in
      postmenopausal women with osteoporosis treated with denosumab.
AB  - In the FREEDOM study, denosumab treatment (60 mg every 6 months) decreased bone
      resorption, increased bone mineral density (BMD), and reduced new vertebral,
      nonvertebral, and hip fractures over 36 months in postmenopausal women with
      osteoporosis. In a subset of these women, hip quantitative computed tomography
      (QCT) was performed at baseline and months 12, 24, and 36. These scans were
      analyzed using Medical Image Analysis Framework (MIAF) software, which allowed
      assessment of total hip integral, trabecular, subcortical, and cortical
      compartments; the cortical compartment was further divided into 2 areas of
      interest (outer and inner cortex). This substudy reports changes in BMD and bone
      mineral content (BMC) from baseline and compared placebo with denosumab over 36
      months of treatment (placebo N=26; denosumab N=36). Denosumab treatment resulted
      in significant improvements in total hip integral volumetric BMD (vBMD) and BMC
      from baseline at each time point. At month 36, the mean percentage increase from
      baseline in total hip integral vBMD and BMC was 6.4% and 4.8%, respectively (both
      p<0.0001). These gains were accounted for by significant increases in vBMD and
      BMC in the trabecular, subcortical, and cortical compartments. In the placebo
      group, total hip integral vBMD and BMC decreased at month 36 from baseline by 
      1.5% and -2.6%, respectively (both p<0.05). The differences between denosumab and
      placebo were also significant at months 12, 24, and 36 for integral, trabecular,
      subcortical, and cortical vBMD and BMC (all p<0.05 to <0.0001). While the largest
      percentage differences occurred in trabecular vBMD and BMC, the largest absolute
      differences occurred in cortical vBMD and BMC. In summary, denosumab
      significantly improved both vBMD and BMC from baseline and placebo, assessed by
      QCT MIAF, in the integral, trabecular, subcortical, and cortical hip
      compartments, all of which are relevant to bone strength.

PMID- 23871854
TI  - Shell damage in the Tehuelche scallop Aequipecten tehuelchus caused by Polydora
      rickettsi (Polychaeta: Spionidae) infestation.
AB  - The different types of shell damage caused to the commercially valuable Tehuelche
      scallop (Aequipecten tehuelchus) by the polychaete Polydora rickettsi are
      described. X-rays, computerized tomography, shell sections, scanning electron
      microscopy, Energy Dispersive X-ray analysis (EDAX), mineralogical analyses and
      geometric morphometrics were applied to that end. Scallop shells presented three
      types of damage: (1) spots, (2) calcareous alterations, and (3) mud blisters.
      Microstructural alterations consisted of a simple conchiolin membranous layer in
      the case of spots, a series of interleaved layers of different degree of
      calcifications in calcareous alterations, and two different surface morphologies
      (muddy and mucous layers) in mud blisters. Damage was localized mainly along
      concentric growth rings, coincidentally with the location of most burrows, as
      shown by X-ray. Mineralogical analysis showed that in all cases (including non
      infested shells) calcite was the calcium carbonate polymorph present. Geometric
      morphometrics showed that only 5% of shape variation was explained by infestation
      with P. rickettsi, irrespective of the type of damage. Number of worms per
      infested shell varied significantly among four beds. Left shells (upward
      oriented) were significantly more affected than right shells, which are in closer
      contact with the bottom. 

PMID- 23871855
TI  - Host-parasite interactions: Marine bivalve molluscs and protozoan parasites,
      Perkinsus species.
AB  - This review assesses and examines the work conducted to date concerning host and
      parasite interactions between marine bivalve molluscs and protozoan parasites,
      belonging to Perkinsus species. The review focuses on two well-studied host
      parasite interaction models: the two clam species, Ruditapes philippinarum and R.
      decussatus, and the parasite Perkinsus olseni, and the eastern oyster,
      Crassostrea virginica, and the parasite Perkinsus marinus. Cellular and humoral
      defense responses of the host in combating parasitic infection, the mechanisms
      (e.g., antioxidant enzymes, extracellular products) employed by the parasite in
      evading host defenses as well as the role of environmental factors in modulating
      the host-parasite interactions are described. 

PMID- 23871856
TI  - In vitro neuroendocrine effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
      the AhR-expressing hypothalamic rat GnV-3 cell line.
AB  - The aryl hydrocarbon receptor (AhR) is involved in a wide variety of biological
      and toxicological responses, including neuroendocrine signaling. Due to the
      complexity of neuroendocrine pathways in e.g. the hypothalamus and pituitary,
      there are limited in vitro models available despite the strong demand for such
      systems to study and predict neuroendocrine effects of chemicals. In this study,
      the applicability of the AhR-expressing rat hypothalamic GnV-3 cell line was
      investigated as a novel model to screen for neuroendocrine effects of AhR ligands
      using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as reference compound. The qRT
      PCR analyses demonstrated the presence of several sets of neurotransmitter
      receptors in the GnV-3 cells. TCDD (10nM) altered neurotransmitter signaling by
      up-regulation of glutamate (Grik2), gamma-amino butyric acid (Gabra2) and
      serotonin (Ht2C) receptor mRNA levels. However, no significant changes in basal
      and serotonin-evoked intracellular Ca(2+) concentration ([Ca(2+)]i) or serotonin
      release were observed. On the other hand, TCDD de-regulated period circadian
      protein homolog 1 (Per1) and gonadotropin releasing hormone (Gnrh) mRNA levels
      within a 24-h time period. Both Per1 and Gnrh genes displayed a similar mRNA
      expression pattern in GnV-3 cells. Moreover, the involvement of AhR in TCDD
      induced alteration of Neuropeptide Y (Npy) gene expression was found and
      confirmed by using siRNA targeted against Ahr in GnV-3 cells. Overall, the
      combined results demonstrate that GnV-3 cells may be a suitable model to predict
      some mechanisms of action and effects of AhR ligands in the hypothalamus. 

PMID- 23871857
TI  - Optimizing SNP microarray probe design for high accuracy microbial genotyping.
AB  - Microarrays to characterize single nucleotide polymorphisms (SNPs) provide a cost
      effective and rapid method (under 24h) to genotype microbes as an alternative to
      sequencing. We developed a pipeline for SNP discovery and microarray design that
      scales to 100's of microbial genomes. Here we tested various SNP probe design
      strategies against 8 sequenced isolates of Bacillus anthracis to compare sequence
      and microarray data. The best strategy allowed probe length to vary within 32-40
      bp to equalize hybridization free energy. This strategy resulted in a call rate
      of 99.52% and concordance rate of 99.86% for finished genomes. Other probe design
      strategies averaged substantially lower call rates (94.65-96.41%) and slightly
      lower concordance rates (99.64-99.80%). These rates were lower for draft than
      finished genomes, consistent with higher incidence of sequencing errors and gaps.
      Highly accurate SNP calls were possible in complex soil and blood backgrounds
      down to 1000 copies, and moderately accurate SNP calls down to 100 spiked copies.
      The closest genome to the spiked strain was correctly identified at only 10
      spiked copies. Discrepancies between sequence and array data did not alter the
      SNP-based phylogeny, regardless of the probe design strategy, indicating that SNP
      arrays can accurately place unsequenced isolates on a phylogeny.

PMID- 23871858
TI  - Current methods for molecular typing of Campylobacter species.
AB  - Campylobacter remains one of the most common bacterial causes of gastroenteritis
      worldwide. Tracking sources of this organism is challenging due to the large
      numbers of human cases, and the prevalence of this organism throughout the
      environment due to growth in a wide range of animal species. Many molecular
      subtyping methods have been developed to characterize Campylobacter species, but
      only a few are commonly used in molecular epidemiology studies. This review
      examines the applicability of these methods, as well as the role that emerging
      whole genome sequencing technologies will play in tracking sources of
      Campylobacter spp. infection. 

PMID- 23871859
TI  - Glass bead cultivation of fungi: combining the best of liquid and agar media.
AB  - Production of bioactive compounds and enzymes from filamentous fungi is highly
      dependent on cultivation conditions. Here we present an easy way to cultivate
      filamentous fungi on glass beads that allow complete control of nutrient supply.
      Secondary metabolite production in Fusarium graminearum and Fusarium solani
      cultivated on agar plates, in shaking liquid culture or on glass beads was
      compared. Agar plate culture and glass bead cultivation yielded comparable
      results while liquid culture had lower production of secondary metabolites. RNA
      extraction from glass beads and liquid cultures was easier than from agar plates
      and the quality was superior. The system allows simple control of nutrient
      availability throughout fungal cultivation. This combined with the ease of
      extraction of nucleic acids and metabolites makes the system highly suitable for
      the study of gene regulation in response to specific nutrient factors. 

PMID- 23871860
TI  - Is "Sigma" purple or green? Bistable grapheme-color synesthesia induced by
      ambiguous characters.
AB  - People with grapheme-color synesthesia perceive specific colors when viewing
      different letters or numbers. Previous studies have suggested that synesthetic
      color experience can be bistable when induced by an ambiguous character. However,
      the exact relationship between processes underlying the identity of an
      alphanumeric character and the experience of the induced synesthetic color has
      not been examined. In the present study, we explored this by focusing on the
      temporal relation of inducer identification and color emergence using inducers
      whose identity could be rendered ambiguous upon rotation of the characters.
      Specifically, achromatic alphabetic letters (W/M) and digits (6/9) were presented
      at varying angles to 9 grapheme-color synesthetes. Results showed that grapheme
      identification and synesthetically perceived grapheme color covary with the
      orientation of the test stimulus and that synesthetes were slower naming the
      experienced color than identifying the character, particularly at intermediate
      angles where ambiguity was greatest. 

PMID- 23871861
TI  - The influence of cognitive and emotional suppression on overgeneral
      autobiographical memory retrieval.
AB  - Over-general autobiographical memory (OAM) retrieval is characterized by
      retrieval of categoric autobiographical memories. According to the CarFAX model,
      this tendency may result from avoidance which functions to protect the person
      against recalling details of upsetting memories. This study tested whether
      avoidance strategies impact on the ability to retrieve specific autobiographical
      memories. Healthy participants (N=51) watched a negative video clip and were
      instructed to either suppress any thought (thought suppression), suppress any
      feeling (emotional inhibition), or think and feel naturally (controls) in
      response to the video. Participants then completed the Autobiographical Memory
      Test. Participants engaging in either thought suppression or emotional inhibition
      retrieved fewer categoric autobiographical memories than controls. These findings
      challenge the affect regulation component of the CarFAX model insofar as they
      suggest that regulatory strategies that aim to reduce awareness of adverse
      emotional memories do not necessarily lead to increased recall of categoric
      autobiographical memories. 

PMID- 23871862
TI  - Relationships between non-pathological dream-enactment and mirror behaviors.
AB  - Dream-enacting behaviors (DEBs) are behavioral expressions of forceful dream
      images often occurring during sleep-to-wakefulness transitions. We propose that
      DEBs reflect brain activity underlying social cognition, in particular, motor
      affective resonance generated by the mirror neuron system. We developed a Mirror
      Behavior Questionnaire (MBQ) to assess some dimensions of mirror behaviors and
      investigated relationships between MBQ scores and DEBs in a large of university
      undergraduate cohort. MBQ scores were normally distributed and described by a
      four-factor structure (Empathy/Emotional Contagion, Behavioral Imitation,
      Sleepiness/Anger Contagion, Motor Skill Imitation). DEB scores correlated
      positively with MBQ total and factor scores even with social desirability,
      somnambulism and somniloquy controlled. Emotion-specific DEB items correlated
      with corresponding emotion-specific MBQ items, especially crying and smiling.
      Results provide preliminary evidence for cross-state relationships between
      propensities for dream-enacting and mirror behaviors--especially behaviors
      involving motor-affective resonance--and our suggestion that motor-affective
      resonance mediates dream-enactment imagery during sleep and emotional empathy
      during waking.

PMID- 23871863
TI  - Predictable and self-initiated visual motion is judged to be slower than computer
      generated motion.
AB  - Self-initiated action effects are often perceived as less intense than identical
      but externally generated stimuli. It is thought that forward models within the
      sensorimotor system pre-activate cortical representations of predicted action
      effects, reducing perceptual sensitivity and attenuating neural responses. As
      self-agency and predictability are seldom manipulated simultaneously in
      behavioral experiments, it is unclear if self-other differences depend on
      predictable action effect contingencies, or if both self- and externally
      generated stimuli are modulated similarly by predictability. We factorially
      combined variation in (1) predictability of action effects, (2) spatial
      congruence, and (3) performance by the self or computer to dissociate these
      influences on a visual discrimination task. Participants performed 2AFC speed
      judgments. Self-initiated motion was judged to be slower than computer-initiated
      motion when action effect contingencies were predictable, while spatial
      congruence influenced speed judgments only when action effect contingencies were
      unpredictable. Results are discussed in relation to current theories of sensory
      attenuation. 

PMID- 23871864
TI  - The prognostic value of end tidal carbon dioxide during cardiac arrest: a
      systematic review.
AB  - INTRODUCTION: Cardiac arrest is a common presentation to the emergency care
      system. The decision to terminate CPR is often challenging to heath care
      providers. An accurate, early predictor of the outcome of resuscitation is
      needed. The purpose of this systematic review is to evaluate the prognostic value
      of ETCO2 during cardiac arrest and to explore whether ETCO2 values could be
      utilised as a tool to predict the outcome of resuscitation. METHOD: Literature
      search was performed using Medline and EMBASE databases to identify studies that
      evaluated the relationship between ETCO2 during cardiac arrest and outcome.
      Studies were thoroughly evaluated and appraised. Summary of evidence and
      conclusions were drawn from this systematic literature review. RESULTS: 23
      observational studies were included. The majority of studies showed that ETCO2
      values during CPR were significantly higher in patients who later developed ROSC
      compared to patients who did not. Several studies suggested that initial ETCO2
      value of more than 1.33 kPa is 100% sensitive for predicting survival making
      ETCO2 value below 1.33 kPa a strong predictor of mortality. These studies however
      had several limitations and the 100% sensitivity for predicting survival was not
      consistent among all studies. CONCLUSION: ETCO2 values during CPR do correlate
      with the likelihood of ROSC and survival and therefore have prognostic value.
      Although certain ETCO2 cut-off values appears to be a strong predictor of
      mortality, the utility of ETCO2 cut-off values during CPR to accurately predict
      the outcome of resuscitation is not fully established. Therefore, ETCO2 values
      cannot be used as a mortality predictor in isolation.

PMID- 23871866
TI  - Prediction of pupylation sites using the composition of k-spaced amino acid
      pairs.
AB  - Pupylation is an important post-translational modification in prokaryotes. A
      prokaryotic ubiquitin-like protein (Pup) is attached to proteins as a signal for
      selective degradation by proteasome. Several proteomics methods have been
      developed for the identification of pupylated proteins and pupylation sites.
      However, pupylation sites of many experimentally identified pupylated proteins
      are still unknown. The development of sequence-based prediction methods can help
      to accelerate the identification of pupylation sites and gain insights into the
      substrate specificity and regulatory functions of pupylation. A novel tool iPUP
      is developed for the computational identification of pupylation sites. A
      composition of k-spaced amino acid pairs is utilized to represent a peptide
      sequence. Top ranked k-spaced amino acid pairs are subsequently selected by using
      a sequential backward feature elimination algorithm. The 10-fold cross-validation
      performance of iPUP trained by using the composition of 150 top ranked k-spaced
      amino acid pairs and support vector machines is 0.83 for the area under receiver
      operating characteristic curve. The importance analysis of k-spaced amino acid
      pairs shows that terminal space-containing pairs are useful for discriminating
      pupylation sites from non-pupylation sites. A sequence analysis confirms that
      lysines close to C-terminus tend to be pupylated. In contrast, lysines close to N
      terminus are less likely to be pupylated. The iPUP tool can predict pupylation
      sites with probability scores for prioritizing promising pupylation sites. Both
      the online server and the standalone software of iPUP are freely available for
      academic use at http://cwtung.kmu.edu.tw/ipup. 

PMID- 23871865
TI  - Sublingual microcirculation is impaired in post-cardiac arrest patients.
AB  - AIM: We hypothesized that microcirculatory dysfunction, similar to that seen in
      sepsis, occurs in post-cardiac arrest patients and that better microcirculatory
      flow will be associated with improved outcome. We also assessed the association
      between microcirculatory dysfunction and inflammatory markers in the post-cardiac
      arrest state. METHODS: We prospectively evaluated the sublingual microcirculation
      in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy
      control patients using Sidestream Darkfield microscopy. Microcirculatory flow was
      assessed using the microcirculation flow index (MFI) at 6 and 24h in the cardiac
      arrest patients, and within 6h of emergency department admission in the sepsis
      and control patients. RESULTS: We evaluated 30 post-cardiac arrest patients, 16
      severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual
      microcirculatory blood flow was significantly impaired in post-cardiac arrest
      patients at 6h (MFI 2.6 [IQR: 2-2.9]) and 24h (2.7 [IQR: 2.3-2.9]) compared to
      controls (3.0 [IQR: 2.9-3.0]; p<0.01 and 0.02, respectively). After adjustment
      for initial APACHE II score, post-cardiac arrest patients had significantly lower
      MFI at 6-h compared to sepsis patients (p<0.03). In the post-cardiac arrest
      group, patients with good neurologic outcome had better microcirculatory blood
      flow as compared to patients with poor neurologic outcome (2.9 [IQR: 2.4-3.0] vs.
      2.6 [IQR: 1.9-2.8]; p<0.03). There was a trend toward higher median MFI at 24h in
      survivors vs. non-survivors (2.8 [IQR: 2.4-3.0] vs. 2.6 [IQR: 2.1-2.8]
      respectively; p<0.09). We found a negative correlation between MFI-6 and vascular
      endothelial growth factor (VEGF) (r=-0.49, p=0.038). However, after Bonferroni
      adjustment for multiple comparisons, this correlation was statistically non
      significant. CONCLUSION: Microcirculatory dysfunction occurs early in post
      cardiac arrest patients. Better microcirculatory function at 24h may be
      associated with good neurologic outcome.

PMID- 23871867
TI  - Hes1 and Hes5 regulate vascular remodeling and arterial specification of
      endothelial cells in brain vascular development.
AB  - The vascular system is the first organ to form in the developing mammalian
      embryo. The Notch signaling pathway is an evolutionarily conserved signaling
      mechanism essential for proper embryonic development in almost all vertebrate
      organs. The analysis of targeted mouse mutants has demonstrated essential roles
      of the Notch signaling pathway in embryonic vascular development. However, Notch
      signaling-deficient mice have so far not been examined in detail in the head
      region. The bHLH genes Hes1 and Hes5 are essential effectors for Notch signaling,
      which regulate the maintenance of progenitor cells and the timing of their
      differentiation in various tissues and organs. Here, we report that endothelial
      specific Hes1 and Hes5 mutant embryos exhibited defective vascular remodeling in
      the brain. In addition, arterial identity of endothelial cells was partially lost
      in the brain of these mutant mice. These data suggest that Hes1 and Hes5 regulate
      vascular remodeling and arterial fate specification of endothelial cells in the
      development of the brain. Hes1 and Hes5 represent critical transducers of Notch
      signals in brain vascular development. 

PMID- 23871868
TI  - The functional role of the frontal cortex in pre-attentive auditory change
      detection.
AB  - Accounts of the functional role of the frontal cortex in pre-attentive auditory
      change detection include attention switching, response inhibition, contrast
      enhancement, and activation of a predictive model. These accounts assume
      different sequential activation patterns between the temporal and frontal
      cortices: Change detection in the auditory areas of the superior temporal cortex
      (STC) followed by inferior frontal cortex (IFC) activation for attention
      switching and response inhibition; STC preceded by IFC activation for contrast
      enhancement; and an IFC-STC-IFC activation sequence for the predictive model. We
      used the event-related optical signal (EROS), which provides a temporal
      resolution of milliseconds and a spatial resolution of 5 to 10mm, combined with
      lagged correlation path modeling to examine the response of the right frontal and
      temporal cortices to auditory duration deviants of varying magnitude. Event
      related potentials (ERPs) were also recorded, as was the slow optical
      (hemodynamic) brain response. The data analyses revealed temporal-frontal,
      frontal-temporal-frontal, and temporal-frontal activation patterns when the
      deviants represented relatively large, medium, and small changes from the
      standard stimulus, respectively. These results indicate that the degree of
      deviance modulates spatio-temporal dynamics within the STC-IFC auditory change
      detection network. 

PMID- 23871869
TI  - Manipulating letter fluency for words alters electrophysiological correlates of
      recognition memory.
AB  - The mechanisms that give rise to familiarity memory have received intense
      research interest. One current topic of debate concerns the extent to which
      familiarity is driven by the same fluency sources that give rise to certain
      implicit memory phenomena. Familiarity may be tied to conceptual fluency, given
      that familiarity and conceptual implicit memory can exhibit similar
      neurocognitive properties. However, familiarity can also be driven by perceptual
      factors, and its neural basis under these circumstances has received less
      attention. Here we recorded brain potentials during recognition testing using a
      procedure that has previously been shown to encourage a reliance on letter
      information when assessing familiarity for words. Studied and unstudied words
      were derived either from two separate letter pools or a single letter pool
      ("letter-segregated" and "normal" conditions, respectively) in a within-subjects
      contrast. As predicted, recognition accuracy was higher in the letter-segregated
      relative to the normal condition. Electrophysiological analyses revealed parietal
      old-new effects from 500-700 ms in both conditions. In addition, a
      topographically dissociable occipital old-new effect from 300-700 ms was present
      in the letter-segregated condition only. In a second experiment, we found that
      similar occipital brain potentials were associated with confident false
      recognition of words that shared letters with studied words but were not
      themselves studied. These findings indicate that familiarity is a multiply
      determined phenomenon, and that the stimulus dimensions on which familiarity is
      based can moderate its neural correlates. Conceptual and perceptual contributions
      to familiarity vary across testing circumstances, and both must be accounted for
      in theories of recognition memory and its neural basis.

PMID- 23871870
TI  - Microbial monooxygenase amperometric biosensor for monitoring of Baeyer-Villiger
      biotransformation.
AB  - A whole-cell amperometric biosensor consisting of genetically engineered
      Escherichia coli immobilised in polyelectrolyte membrane onto a miniaturised
      oxygen electrode was developed and used for monitoring of biotransformation based
      on Baeyer-Villiger oxidation. Baeyer-Villiger oxidation is commonly performed
      using microorganisms overexpressing Baeyer-Villiger monooxygenase enabling the
      production of enantiopure lactones or esters used in pharmaceutical industry. The
      biorecognition element, genetically modified E. coli overexpressing either
      cyclopentanone monooxygenase or cyclohexanone monooxygenase was immobilised in
      the form of solid polyelectrolyte complex gel membrane made of cellulose
      sulphate, sodium alginate and poly(methylene-co-guanidine) and attached to the
      surface of miniaturised oxygen electrode. The time response of the biosensor was
      30s, the linear range of the calibration curve (R(2)=0.9993) was 8-130 MUM and
      the sensitivity was 1.8 nA MUM(-1) (RSD=5.0%) for substrate of Baeyer-Villiger
      oxidation (+/-)-cis-bicyclo[3.2.0]hept-2-en-6-one as analyte. The biosensor
      sensitivity was assessed for two other commercially available substrates, 4
      methylcyclohexanone and 3-methylcyclohexanone. No interferences from ampicillin,
      citric acid, acetic acid, ethanol, methanol, glucose and products of Baeyer
      Villiger oxidation (1R, 5S)-3-oxabicyclo[3.3.0]oct-6-en-2-one and (1S, 5R)-2
      oxabicyclo[3.3.0]oct-6-en-3-one were detected. After 1 week of storage at 4
      degrees C the biosensor sensitivity was without changes. The biosensor was
      employed for monitoring of Baeyer-Villiger biotransformation and the results were
      correlated with gas chromatography. Till now, this is the first described
      biosensor based on Baeyer-Villiger monooxygenase and the first reported
      application of biosensor for monitoring of biotransformation based on Baeyer
      Villiger oxidation.

PMID- 23871871
TI  - Lysozyme detection on aptamer functionalized graphene-coated SPR interfaces.
AB  - The paper reports on a surface plasmon resonance (SPR)-based approach for the
      sensitive and selective detection of lysozyme. The SPR sensor consists of a 50 nm
      gold film coated with a thin film of reduced graphene oxide (rGO) functionalized
      with anti-lysozyme DNA aptamer. The SPR chip coating with rGO matrix was achieved
      through electrophoretic deposition of graphene oxide (GO) at 150 V.
      Electrophoretic deposition resulted in partial reduction of GO to rGO with a
      thickness depending on the deposition time. For very short time pulses of 20 s,
      the resulting rGO film had a thickness of several nanometers and was appropriate
      for SPR sensing. The utility of the graphene-based SPR sensor for the selective
      and sensitive detection of proteins was demonstrated using lysozyme as model
      protein. Functionalization of rGO matrix with anti-lysozyme DNA aptamer through
      pi-stacking interactions allowed selective SPR detection of lysozyme. The
      graphene-based SPR biosensor provides a means for the label-free, concentration
      dependent and selective detection of lysozymes with a detection limit of 0.5 nM.

PMID- 23871872
TI  - Electroactive species-doped poly(3,4-ethylenedioxythiophene) films: enhanced
      sensitivity for electrochemical simultaneous determination of vitamins B2, B6 and
      C.
AB  - Herein, functionalized PEDOT films were prepared by incorporation of two
      electroactive species, ferrocenecarboxylic acid (Fc(-)) and ferricyanide
      (Fe(CN)6(4-)) as doping anions during the electropolymerization of PEDOT at
      glassy carbon electrodes (GCEs) from aqueous solution. The electrochemically
      synthesized electroactive species-doped PEDOT films have been carefully
      characterized by scanning electron microscopy (SEM), FTIR and UV/Vis spectra and
      various electrochemical techniques. Such nanostructured films combined the
      advantages of PEDOT (high conductivity and stability) together with electroactive
      species (good electrochemical activity) and were applied as electrochemical
      sensors for simultaneous determination of vitamin B2 (VB2), vitamin B6 (VB6) and
      vitamin C (VC). The results showed that the oxidation peak currents of vitamins
      obtained at the GCEs modified with electroactive species-doped PEDOT films were
      much higher than those at the ClO4(-)-doped PEDOT films and bare GCEs. The
      experiment results also illustrated that the sensors possessed high selectivity
      with no interference from other potential competing species. Moreover, the
      proposed sensors were successfully employed for the determination of vitamins in
      orange juice samples with satisfactory results. 

PMID- 23871873
TI  - Graphene-based nanoprobes and a prototype optical biosensing platform.
AB  - Biochemical and biomedical applications of graphene are critically dependent on
      the interaction between biomolecules and the nanomaterial. In this work, we
      developed a graphene-based signal-amplification nanoprobe by combining anti
      immunoglobulin G (anti-IgG) and horseradish peroxidase (HRP) with graphene oxide
      (GO). The structure and function of HRP in the nano-interface of GO were firstly
      investigated, which demonstrated that the enzyme retained 78% of its native
      activity and 77% of its native alpha-helix content. HRP and anti-IgG were then co
      adsorbed onto GO to form bifunctional nanoprobes. The nanoprobes provide both
      improved binding ability and signal-amplification ability. Comparing with
      conventional bioconjugates such as enzyme-linked antibody, co-adsorption could
      avoid chemical conjugation between biomolecules, keeping their bioactivity well.
      As an example for their application, the nanoprobes were used to obtain amplified
      signals in a sandwich-type immunoassay for cancer marker, instead of conventional
      colorimetric conjugates. This approach provided a detection limit of 10 pg/mL
      alpha-fetoprotein (AFP), which was much more sensitive than conventional enzyme
      linked immunosorbent assay (ELISA) methods. The easily fabricated GO-based
      nanoprobes have the potential to become universal probes for molecular
      diagnostics.

PMID- 23871874
TI  - A simple and sensitive biosensor strain for detecting toxoflavin using beta
      galactosidase activity.
AB  - In this study, we developed a simple and sensitive biosensor for the
      determination of toxoflavin (which is toxic to various plants, fungi, animals,
      and bacteria) in natural samples based on beta-galactosidase activity. The
      proposed toxoflavin detection method for toxin-producing bacteria or toxin
      contaminated foods is simple and cost effective. Burkholderia glumae, a species
      known to cause rice grain rot and wilt in various field crops, produces
      toxoflavin under the control of a LysR-type transcriptional regulator ToxR and
      its ligand toxoflavin. As the expression of toxoflavin biosynthetic genes
      requires toxoflavin as a co-activator of ToxR, a novel biosensor stain was
      constructed based on lacZ reporter gene integration into the first gene of the
      toxoflavin biosynthesis operon, toxABCDE of B. glumae. The biosensor was composed
      of a sensor strain (COK71), substrates (X-gal or ONPG), and culture medium,
      without any complex preparation process. We demonstrated that the biosensor
      strain is highly specific to toxoflavin, and can quantify relative amounts of
      toxoflavin compared with known concentrations of toxoflavin. The proposed method
      was reliable and simple; samples containing 50-500 nM of toxoflavin could be
      analyzed. More importantly, the proposed biosensor strain could identify
      toxoflavin-producing bacteria in real samples. The excellent performance of this
      biosensor is useful for diagnostic purposes, such as detecting toxoflavin
      contaminated foods and environmental samples.

PMID- 23871875
TI  - Molecularly imprinted polymer grafted paper-based multi-disk micro-disk plate for
      chemiluminescence detection of pesticide.
AB  - The detection of pesticides has attracted considerable attention in numerous
      fields, such as environmental monitoring and food safety. Although traditional
      sensors for pesticides have been widely explored due to their high sensitivity
      and specificity, it is still challenging to develop a low-cost, portable, fast,
      and easy-to-use detection method for the public use at home or in the field. To
      address these challenges, herein, we report a novel paper-based molecular
      imprinted polymer (MIP)-grafted multi-disk micro-disk plate (P-MIP-MMP) for
      sensitive and specific chemiluminescence (CL) detection of pesticides through an
      indirect competitive assay using 2,4-dichlorophenoxyacetic acid (2,4-D) as a
      proof-of-concept analyte. The MIP-grafted paper disks were prepared by a simple
      in situ polymerization of MIP layer on the surface of cellulose fibers in paper.
      The quantification mechanism of this P-MIP-MMP is based on a competition between
      free 2,4-D and tobacco peroxidase (TOP) labeled 2,4-D and the enzyme catalyzed CL
      emission from the luminol-TOP-H2O2 CL system. At optimal conditions, this P-MIP
      MMP can detect 2,4-D at the concentration of femtomolar level. This approach
      provided a powerful protocol for simple, low-cost, rapid, and high-throughput
      detection of pesticides in real samples with satisfactory results for use in
      areas such as food inspection and environmental monitoring. 

PMID- 23871876
TI  - Digital simulation of chronoamperometry at an electrode within a hemispherical
      polymer drop containing an enzyme: comparison of a hemispherical with a flat disk
      electrode.
AB  - Current-time and steady state current behaviour was simulated for the cases of a
      hemispherical and flat inlaid disk electrodes located under a hemispherical
      polymer drop containing an enzyme which converts a substrate diffusing into the
      drop into a product that is electroactive at the electrode. As well, a
      cylindrical electrode with length much greater than its diameter and coated with
      a layer of polymer/enzyme was treated. The ratio of steady state currents at the
      hemispherical to the disk electrode is not, as has sometimes been assumed, always
      equal to pi/2; indeed this is only approached for polymer drops with large
      spillover ratio, that is, having a radius much larger than that of the
      electrodes. Steady state currents for all electrode geometries (including the
      cylinder) go through a maximum for some spillover ratio and then approach a
      constant value for larger spillover ratios. This constant value is the same as
      that for the diffusion limited current in a semi-infinite medium. For a
      cylindrical electrode, the steady state current tends towards zero for large
      spillover ratios. 

PMID- 23871877
TI  - Interlimb coordination during the stance phase of gait in subjects with stroke.
AB  - OBJECTIVE: To analyze the relation between contralesional and ipsilesional limbs
      in subjects with stroke during step-to-step transition of walking. DESIGN:
      Observational, transversal, analytical study with a convenience sample. SETTING:
      Physical medicine and rehabilitation clinic. PARTICIPANTS: Subjects (n=16) with
      poststroke hemiparesis with the ability to walk independently and healthy
      controls (n=22). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Bilateral
      lower limbs electromyographic activity of the soleus (SOL), gastrocnemius
      medialis, tibialis anterior, biceps femoris, rectus femoris, and vastus medialis
      (VM) muscles and the ground reaction force were analyzed during double-support
      and terminal stance phases of gait. RESULTS: The propulsive impulse of the
      contralesional trailing limb was negatively correlated with the braking impulse
      of the leading limb during double support (r=-.639, P=.01). A moderate functional
      relation was observed between thigh muscles (r=-.529, P=.035), and a strong and
      moderate dysfunctional relation was found between the plantar flexors of the
      ipsilesional limb and the vastus medialis of the contralesional limb,
      respectively (SOL-VM, r=-.80, P<.001; gastrocnemius medialis-VM, r=-.655,
      P=.002). Also, a functional moderate negative correlation was found between the
      SOL and rectus femoris muscles of the ipsilesional limb during terminal stance
      and between the SOL (r=-.506, P=.046) and VM (r=-.518, P=.04) muscles of the
      contralesional limb during loading response, respectively. The trailing limb
      relative impulse contribution of the contralesional limb was lower than the
      ipsilesional limb of subjects with stroke (P=.02) and lower than the relative
      impulse contribution of the healthy limb (P=.008) during double support.
      CONCLUSIONS: The findings obtained suggest that the lower performance of the
      contralesional limb in forward propulsion during gait is related not only to
      contralateral supraspinal damage but also to a dysfunctional influence of the
      ipsilesional limb.

PMID- 23871878
TI  - Effects of food-deprivation and refeeding on the regulation and sources of blood
      glucose appearance in European seabass (Dicentrarchus labrax L.).
AB  - Sources of blood glucose in European seabass (initial weight 218.0+/-43.0g;
      mean+/-S.D., n=18) were quantified by supplementing seawater with deuterated
      water (5%-(2)H2O) for 72h and analyzing blood glucose (2)H-enrichments by (2)H
      NMR. Three different nutritional states were studied: continuously fed, 21-day of
      fast and 21-day fast followed by 3days of refeeding. Plasma glucose levels (mM)
      were 10.7+/-6.3 (fed), 4.8+/-1.2 (fasted), and 9.3+/-1.4 (refed) (means+/-S.D.,
      n=6), showing poor glycemic control. For all conditions, (2)H-enrichment of
      glucose position 5 was equivalent to that of position 2 indicating that blood
      glucose appearance from endogenous glucose 6-phosphate (G6P) was derived by
      gluconeogenesis. G6P-derived glucose accounted for 65+/-7% and 44+/-10% of blood
      glucose appearance in fed and refed fish, respectively, with the unlabeled
      fraction assumed to be derived from dietary carbohydrate (35+/-7% and 56+/-10%,
      respectively). For 21-day fasted fish, blood glucose appearance also had
      significant contributions from unlabeled glucose (52+/-16%) despite the
      unavailability of dietary carbohydrates. To assess the role of hepatic enzymes in
      glycemic control, activity and mRNA levels of hepatic glucokinase (GK) and
      glucose 6-phosphatase (G6Pase) were assessed. Both G6Pase activity and expression
      declined with fasting indicating the absence of a classical counter-regulatory
      stimulation of hepatic glucose production in response to declining glucose
      levels. GK activities were basal during fed and fasted conditions, but were
      strongly stimulated by refeeding. Overall, hepatic G6Pase and GK showed limited
      capacity in regulating glucose levels between feeding and fasting states. 

PMID- 23871879
TI  - The molecular basis for the inhibition of phosphodiesterase-4D by three natural
      resveratrol analogs. Isolation, molecular docking, molecular dynamics
      simulations, binding free energy, and bioassay.
AB  - The phosphodiesterase-4 (PDE4) enzyme is a promising therapeutic target for
      several diseases. Our previous studies found resveratrol and moracin M to be
      natural PDE4 inhibitors. In the present study, three natural resveratrol analogs
      [pterostilbene, (E)-2',3,5',5-tetrahydroxystilbene (THSB), and oxyresveratrol]
      are structurally related to resveratrol and moracin M, but their inhibition and
      mechanism against PDE4 are still unclear. A combined method consisting of
      molecular docking, molecular dynamics (MD) simulations, binding free energy, and
      bioassay was performed to better understand their inhibitory mechanism. The
      binding pattern of pterostilbene demonstrates that it involves
      hydrophobic/aromatic interactions with Phe340 and Phe372, and forms hydrogen
      bond(s) with His160 and Gln369 in the active site pocket. The present work also
      reveals that oxyresveratrol and THSB can bind to PDE4D and exhibits less negative
      predicted binding free energies than pterostilbene, which was qualitatively
      validated by bioassay (IC50=96.6, 36.1, and 27.0MUM, respectively). Additionally,
      a linear correlation (R(2)=0.953) is achieved for five PDE4D/ligand complexes
      between the predicted binding free energies and the experimental counterparts
      approximately estimated from their IC50 values (~RT ln IC50). Our results imply
      that hydrophobic/aromatic forces are the primary factors in explaining the
      mechanism of inhibition by the three products. Results of the study help to
      understand the inhibitory mechanism of the three natural products, and thus help
      the discovery of novel PDE4 inhibitors from resveratrol, moracin M, and other
      natural products. 

PMID- 23871880
TI  - Unimpaired discrimination of fearful prosody after amygdala lesion.
AB  - Prosody (i.e. speech melody) is an important cue to infer an interlocutor's
      emotional state, complementing information from face expression and body posture.
      Inferring fear from face expression is reported as impaired after amygdala
      lesions. It remains unclear whether this deficit is specific to face expression,
      or is a more global fear recognition deficit. Here, we report data from two twins
      with bilateral amygdala lesions due to Urbach-Wiethe syndrome and show they are
      unimpaired in a multinomial emotional prosody classification task. In a two
      alternative forced choice task, they demonstrate increased ability to
      discriminate fearful and neutral prosody, the opposite of what would be expected
      under an hypothesis of a global role for the amygdala in fear recognition. Hence,
      we provide evidence that the amygdala is not required for recognition of fearful
      prosody. 

PMID- 23871881
TI  - Representations of individuals in ventral temporal cortex defined by faces and
      biographies.
AB  - The fusiform gyrus responds more strongly to faces than to other categories of
      objects. This response could reflect either categorical detection of faces or
      recognition of particular facial identities. Recent fMRI studies have attempted
      to address the question of what information is encoded in these regions, but have
      reported mixed results. We tested whether the creation of richer identity
      representations via training on visual and social information, and the use of an
      adaptation design, would reveal more robust representations of these identities
      in ventral temporal cortex. Examining the patterns of activation across voxels in
      bilateral fusiform gyri, we identified unique patterns for particular identities.
      Attaching distinctive biographical information to identities did not increase the
      strength of these representations, but did produce a grouping effect: faces
      associated with the same amount of biographical information were represented more
      similarly to each other. These results are consistent with the possibility that
      identity exemplars are represented in posterior visual areas best known for their
      role in representing categorical information, and suggest that these areas may be
      sensitive to some forms of non-visual information, including from the social
      domain. 

PMID- 23871882
TI  - T1 mapping for diffuse myocardial fibrosis: a key biomarker in cardiac disease?

PMID- 23871883
TI  - Basic research on myocarditis: superb but unrequited.

PMID- 23871884
TI  - An arrhythmogenic right atrial diverticulum resected through a minimally invasive
      approach without cardiopulmonary bypass.

PMID- 23871885
TI  - Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic
      right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation
      carriers.
AB  - OBJECTIVES: This study sought to determine how exercise influences penetrance of
      arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) among patients
      with desmosomal mutations. BACKGROUND: Although animal models and anecdotal
      evidence suggest that exercise is a risk factor for ARVD/C, there have been no
      systematic human studies. METHODS: Eighty-seven carriers (46 male; mean age, 44
      +/- 18 years) were interviewed about regular physical activity from 10 years of
      age. The relationship of exercise with sustained ventricular arrhythmia
      (ventricular tachycardia/ventricular fibrillation [VT/VF]), stage C heart failure
      (HF), and meeting diagnostic criteria for ARVD/C (2010 Revised Task Force
      Criteria [TFC]) was studied. RESULTS: Symptoms developed in endurance athletes (N
      = 56) at a younger age (30.1 +/- 13.0 years vs. 40.6 +/- 21.1 years, p = 0.05);
      they were more likely to meet TFC at last follow-up (82% vs. 35%, p < 0.001) and
      have a lower lifetime survival free of VT/VF (p = 0.013) and HF (p = 0.004).
      Compared with those who did the least exercise per year (lowest quartile) before
      presentation, those in the second (odds ratio [OR]: 6.64, p = 0.013), third (OR:
      16.7, p = 0.001), and top (OR: 25.3, p < 0.0001) quartiles were increasingly
      likely to meet TFC. Among 61 individuals who did not present with VT/VF, the 13
      subjects experiencing a first VT/VF event over a mean follow-up of 8.4 +/- 6.7
      years were all endurance athletes (p = 0.002). Survival from a first VT/VF event
      was lowest among those who exercised most (top quartile) both before (p = 0.036)
      and after (p = 0.005) clinical presentation. Among individuals in the top
      quartile, a reduction in exercise decreased VT/VF risk (p = 0.04). CONCLUSIONS:
      Endurance exercise and frequent exercise increase the risk of VT/VF, HF, and
      ARVD/C in desmosomal mutation carriers. These findings support exercise
      restriction for these patients.

PMID- 23871887
TI  - Prevalence of anomalous coronary arteries in pulmonary atresia with ventricular
      septal defect and major aortopulmonary collaterals.

PMID- 23871886
TI  - Evaluation of age-related interstitial myocardial fibrosis with cardiac magnetic
      resonance contrast-enhanced T1 mapping: MESA (Multi-Ethnic Study of
      Atherosclerosis).
AB  - OBJECTIVES: This study sought to determine the relationship of cardiovascular
      magnetic resonance (CMR) measures of tissue composition to age in the Multi
      Ethnic Study of Atherosclerosis (MESA). BACKGROUND: Animal and human studies have
      demonstrated increased collagen deposition in senescent hearts. New CMR indices
      of tissue composition by using T1 mapping are sensitive to the presence of
      myocardial fibrosis. METHODS: A total of 1,231 study participants (51% women; age
      range 54 to 93 years) of the MESA cohort were evaluated with T1 mapping by using
      1.5-T CMR scanners. None of the participants had focal scar on delayed
      enhancement CMR. Single-slice T1 mapping was performed at the midventricular
      level before and at 12- and 25-min delay after administration of gadolinium
      contrast by using a modified Look-Locker inversion recovery sequence. The
      partition coefficient was determined by the slope of the linear relationship of
      (1/T1myo vs. 1/T1blood). The extracellular volume fraction (ECV) was derived
      accounting for the hematocrit level. Multivariable regression analyses were
      performed, adjusting for traditional risk factors and left ventricular structure.
      RESULTS: Women had significantly greater partition coefficient, ECV, and
      precontrast T1 than men, as well as lower post-contrast T1 values (all p < 0.05).
      In general, linear regression analyses demonstrated that greater partition
      coefficient, pre-contrast T1 values, and ECV were associated with older age in
      men (multivariate regression coefficients = 0.01; 5.9 ms; and 1.04% per 10 years'
      change; all p < 0.05). ECV was also significantly associated with age in women
      after multivariable adjustments. CONCLUSIONS: CMR parameters that have been
      associated with myocardial fibrosis were related to older age in the MESA study.
      Women had higher ECV than men but less ECV change over time.

PMID- 23871889
TI  - Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular
      health, and all-cause mortality.
AB  - Coffee, after water, is the most widely consumed beverage in the United States,
      and is the principal source of caffeine intake among adults. The biological
      effects of coffee may be substantial and are not limited to the actions of
      caffeine. Coffee is a complex beverage containing hundreds of biologically active
      compounds, and the health effects of chronic coffee intake are wide ranging. From
      a cardiovascular (CV) standpoint, coffee consumption may reduce the risk of type
      2 diabetes mellitus and hypertension, as well as other conditions associated with
      CV risk such as obesity and depression; but it may adversely affect lipid
      profiles depending on how the beverage is prepared. Regardless, a growing body of
      data suggests that habitual coffee consumption is neutral to beneficial regarding
      the risks of a variety of adverse CV outcomes including coronary heart disease,
      congestive heart failure, arrhythmias, and stroke. Moreover, large
      epidemiological studies suggest that regular coffee drinkers have reduced risks
      of mortality, both CV and all-cause. The potential benefits also include
      protection against neurodegenerative diseases, improved asthma control, and lower
      risk of select gastrointestinal diseases. A daily intake of ~2 to 3 cups of
      coffee appears to be safe and is associated with neutral to beneficial effects
      for most of the studied health outcomes. However, most of the data on coffee's
      health effects are based on observational data, with very few randomized,
      controlled studies, and association does not prove causation. Additionally, the
      possible advantages of regular coffee consumption have to be weighed against
      potential risks (which are mostly related to its high caffeine content) including
      anxiety, insomnia, tremulousness, and palpitations, as well as bone loss and
      possibly increased risk of fractures. 

PMID- 23871888
TI  - Protease-activated receptor-2 regulates the innate immune response to viral
      infection in a coxsackievirus B3-induced myocarditis.
AB  - OBJECTIVES: This study sought to evaluate the role of protease-activated receptor
      2 (PAR2) in coxsackievirus B3 (CVB3)-induced myocarditis. BACKGROUND: An
      infection with CVB3 leads to myocarditis. PAR2 modulates the innate immune
      response. Toll-like receptor-3 (TLR3) is crucial for the innate immune response
      by inducing the expression of the antiviral cytokine interferon-beta (IFNbeta).
      METHODS: To induce myocarditis, wild-type (wt) and PAR2 knockout (ko) mice were
      infected with 10(5) plaque-forming units CVB3. Mice underwent hemodynamic
      measurements with a 1.2-F microconductance catheter. Wt and PAR2ko hearts and
      cardiac cells were analyzed for viral replication and immune response with plaque
      assay, quantitative polymerase chain reaction, Western blot, and
      immunohistochemistry. RESULTS: Compared with wt mice, PAR2ko mice and
      cardiomyocytes exhibited a reduced viral load and developed no myocarditis after
      infection with CVB3. Hearts and cardiac fibroblasts from PAR2ko mice expressed
      higher basal levels of IFNbeta than wt mice did. Treatment with CVB3 and
      polyinosinic:polycytidylic acid led to higher IFNbeta expression in PAR2ko than
      in wt fibroblasts and reduced virus replication in PAR2ko fibroblasts was
      abrogated by neutralizing IFNbeta antibody. Overexpression of PAR2 reduced the
      basal IFNbeta expression. Moreover, a direct interaction between PAR2 and Toll
      like receptor 3 was observed. PAR2 expression in endomyocardial biopsies of
      patients with nonischemic cardiomyopathy was positively correlated with
      myocardial inflammation and negatively with IFNbeta expression and left
      ventricular ejection fraction. CONCLUSIONS: PAR2 negatively regulates the innate
      immune response to CVB3 infection and contributes to myocardial dysfunction. The
      antagonism of PAR2 is of therapeutic interest to strengthen the antiviral
      response after an infection with a cardiotropic virus.

PMID- 23871890
TI  - Primary giant cardiac cavernous hemangioma in right mediastinum.

PMID- 23871891
TI  - Neurocysticercosis in Europe: Still a public health concern not only for imported
      cases.
AB  - Neurocysticercosis (NCC), a parasitic disease caused by the larvae of the cestode
      Taenia solium, is the most frequent parasitic disease of the central nervous
      system (CNS) in the world and the leading cause of secondary epilepsy in Central
      and South America, East and South Asia, and sub-Saharan Africa. It is endemic in
      many low- and middle-income countries of the world. Due to increased travels and
      immigration, NCC may be diagnosed also in non-endemic areas. In fact, tapeworm
      carriers from endemic zones can transmit infection to other citizens or arrive
      already suffering NCC. This phenomenon, occurred first in USA during the last 30
      years, has been also observed in Europe, as well as in Australia, Canada, Israel,
      Japan and Muslim countries of the Arab World. Actually, concerning Europe,
      although, in some areas only few cases have been described, nevertheless the
      prevalence of NCC may be considered increasing, especially in Spain and Portugal.
      We reviewed the literature on the burden of NCC in Europe, by a search of PubMed
      regarding papers from 1970 to present. We only considered on PubMed published and
      available papers in English, French, Italian, and Spanish, the languages
      understood by the authors. One hundred seventy six cases of NCC have been
      reported in seventeen European countries (Austria, Belgium, Denmark, Finland,
      France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Netherlands, Sweden,
      United Kingdom, and Croatia, Norway, Switzerland). A particular epidemic
      situation is present in Spain and Portugal. In fact, we collected data that show,
      in Spain, an increasing incidence both in immigrated patients and in those which
      were born in certain Spanish geographical areas and, in Portugal, prevalence
      similar to that observed in endemic areas. Globally, it is clear that as a result
      of increased migrations and travels from endemic regions, NCC is becoming an
      emerging public health problem in high-income countries, particularly affecting
      communities where hygiene conditions are poor and sub-sequentially the parasite
      can spread from human to human through eggs even in absence of a travel to the
      tropics. NCC is a preventable disease, it derives that it's important to acquire
      a great consciousness of the epidemiology and to implement accurate surveillance
      systems. 

PMID- 23871892
TI  - Generation of a highly active folding enzyme by combining a parvulin-type prolyl
      isomerase from SurA with an unrelated chaperone domain.
AB  - Parvulins are small prolyl isomerases and serve as catalytic domains of folding
      enzymes. SurA (survival protein A) from the periplasm of Escherichia coli
      consists of an inactive (Par1) and an active (Par2) parvulin domain as well as a
      chaperone domain. In the absence of the chaperone domain, the folding activity of
      Par2 is virtually abolished. We created a chimeric protein by inserting the
      chaperone domain of SlyD, an unrelated folding enzyme from the FKBP family, into
      a loop of the isolated Par2 domain of SurA. This increased its folding activity
      450-fold to a value higher than the activity of SurA, in which Par2 is linked
      with its natural chaperone domain. In the presence of both the natural and the
      foreign chaperone domain, the folding activity of Par2 was 1500-fold increased.
      Related and unrelated chaperone domains thus are similarly efficient in enhancing
      the folding activity of the prolyl isomerase Par2. A sequence analysis of various
      chaperone domains suggests that clusters of exposed methionine residues in mobile
      chain regions might be important for a generic interaction with unfolded protein
      chains. This binding is highly dynamic to allow frequent transfer of folding
      protein chains between chaperone and catalytic domains. 

PMID- 23871893
TI  - Effect of C-terminal sequence on competitive semaphorin binding to neuropilin-1.
AB  - Neuropilins (Nrp) are type I transmembrane proteins that function as receptors
      for vascular endothelial growth factor (VEGF) and class III Semaphorin (Sema3)
      ligand families. Sema3s function as potent endogenous angiogenesis inhibitors but
      require proteolytically processing by furin to compete with VEGF for Nrp binding.
      This processing liberates a C-terminal arginine (CR) that is necessary for
      binding to the b1 domain of Nrp, a common feature shared by Nrp ligands. The CR
      is necessary but not sufficient for potent Nrp inhibition, and the role of
      upstream residues is unknown. We demonstrate that the second-to-last residue (C
      1), immediately upstream of the CR, plays a significant role in controlling
      competitive ligand binding by orienting the C-terminus for productive Nrp
      binding. With the use of a peptide library derived from Sema3F, C-1 residues that
      preferentially adopt an extended bound-like conformation, including proline and
      beta-branched amino acids, were found to produce the most avid competitors.
      Consistent with this, analysis of the binding thermodynamics revealed that more
      favorable entropy is responsible for the observed binding enhancement of C-1
      proline. We further tested the effect of the C-1 residue on Sema3F processing by
      furin and found an inverse relationship between processing and inhibitory
      potency. Analysis of all Sema3 family members reveals two non-equivalent furin
      processing sites differentiated by the presence of either a C-1 proline or a C-1
      arginine and resulting in up to a 40-fold difference in potency. These data
      reveal a novel regulatory mechanism of Sema3 activity and define a fundamental
      mechanism for preferential Nrp binding. 

PMID- 23871894
TI  - Dimer dynamics and filament organization of the bacterial cell division protein
      FtsA.
AB  - FtsA is a bacterial actin homolog and one of the core proteins involved in cell
      division. While previous studies have demonstrated the capability of FtsA to
      polymerize, little is known about its polymerization state in vivo or if
      polymerization is necessary for FtsA function. Given that one function of FtsA is
      to tether FtsZ filaments to the membrane, in vivo polymerization of FtsA imposes
      geometric constraints and requires a specific polymer curvature direction. Here,
      we report a series of molecular dynamics simulations probing the structural
      dynamics of FtsA as a dimer and as a tetrameric single filament. We found that
      the FtsA polymer exhibits a preferred bending direction that would allow for its
      placement parallel with FtsZ polymers underneath the cytoplasmic membrane. We
      also identified key interfacial amino acids that mediate FtsA-FtsA interaction
      and propose that some amino acids play more critical roles than others. We
      performed in silico mutagenesis on FtsA and demonstrated that, while a moderate
      mutation at the polymerization interface does not significantly affect polymer
      properties such as bending direction and association strength, more drastic
      mutations change both features and could lead to non-functional FtsA. 

PMID- 23871895
TI  - The N-terminal extension of UBE2E ubiquitin-conjugating enzymes limits chain
      assembly.
AB  - Protein ubiquitylation depends upon the concerted action of ubiquitin-conjugating
      enzymes (E2s) and ubiquitin ligases (E3s). All E2s have a conserved ubiquitin
      conjugating (UBC) domain but many have variable extensions N- and C-terminal to
      the UBC domain. For many E2s, the function of the extension is not well
      understood. Here, we show that the N-terminal extension of the UBE2E proteins
      regulates formation of polyubiquitin chains by the processive UBC domain. Target
      proteins are therefore monoubiquitylated by full-length UBE2E, whereas the UBC
      domain alone polyubiquitylates proteins. Although the N-terminal extension of
      UBE2E1 is largely disordered in solution, these residues have a critical role in
      limiting chain building, and when fused to the highly processive E2, UBE2D2,
      ubiquitylation is limited. For some E2s, interaction of ubiquitin with the
      'backside' of the UBC domain promotes polyubiquitylation. However, interaction of
      ubiquitin with the backside of the UBC domain of UBE2E1 does not appear to be
      important for processivity. This study underscores the importance of studying
      full-length E2 proteins and not just the highly conserved core domain. 

PMID- 23871896
TI  - Effect of metal loading and subcellular pH on net charge of superoxide dismutase
      1.
AB  - The net charge of a folded protein is hypothesized to influence myriad
      biochemical processes (e.g., protein misfolding, electron transfer, molecular
      recognition); however, few tools exist for measuring net charge and this elusive
      property remains undetermined--at any pH--for nearly all proteins. This study
      used lysine-acetyl "protein charge ladders" and capillary electrophoresis to
      measure the net charge of superoxide dismutase-1 (SOD1)--whose aggregation causes
      amyotrophic lateral sclerosis (ALS)--as a function of coordinated metal ions and
      pH. The net negative charge of apo-SOD1 was similar to predicted values; however,
      the binding of a single Zn(2+) or Cu(2+) ion reduced the net negative charge by a
      greater magnitude than predicted (i.e., ~4 units, instead of 2), whereas the SOD1
      protein underwent charge regulation upon binding 2-4 metal ions. From pH5 to pH8
      (i.e., a range consistent with the multiple subcellular loci of SOD1), the holo
      SOD1 protein underwent smaller fluctuations in net negative charge than predicted
      (i.e., ~3 units, instead of ~14) and did not undergo charge inversion at its
      isoelectric point (pI=5.3) but remained anionic. The regulation of SOD1 net
      charge along its pathways of metal binding, and across solvent pH, provides
      insight into its metal-induced maturation and enzymatic activity (which remains
      diffusion-limited across pH5-8). The anionic nature of holo-SOD1 across
      subcellular pH suggests that ~45 different ALS-linked mutations to SOD1 will
      reduce its net negative charge regardless of subcellular localization.

PMID- 23871897
TI  - Fast and accurate quantification using Genetic Algorithm optimized 1H-13C
      refocused constant-time INEPT.
AB  - Using Genetic Algorithm, a global optimization method inspired by nature's
      evolutionary process, we have improved the quantitative refocused constant-time
      INEPT experiment (Q-INEPT-CT) of Makela et al. (JMR 204 (2010) 124-130) with
      various optimization constraints. The improved 'average polarization transfer'
      and 'min-max difference' of new delay sets effectively reduces the experimental
      time by a factor of two (compared with Q-INEPT-CT, Makela et al.) without
      compromising on accuracy. We also discuss a quantitative spectral editing
      technique based on average polarization transfer. 

PMID- 23871898
TI  - Spectrally edited 2D 13C-13C NMR spectra without diagonal ridge for
      characterizing 13C-enriched low-temperature carbon materials.
AB  - Two robust combinations of spectral editing techniques with 2D (13)C-(13)C NMR
      have been developed for characterizing the aromatic components of (13)C-enriched
      low-temperature carbon materials. One method (exchange with protonated and
      nonprotonated spectral editing, EXPANSE) selects cross peaks of protonated and
      nearby nonprotonated carbons, while the other technique, dipolar-dephased double
      quantum/single-quantum (DQ/SQ) NMR, selects signals of bonded nonprotonated
      carbons. Both spectra are free of a diagonal ridge, which has many advantages:
      Cross peaks on the diagonal or of small intensity can be detected, and residual
      spinning sidebands or truncation artifacts associated with the diagonal ridge are
      avoided. In the DQ/SQ experiment, dipolar dephasing of the double-quantum
      coherence removes protonated-carbon signals; this approach also eliminates the
      need for high-power proton decoupling. The initial magnetization is generated
      with minimal fluctuation by combining direct polarization, cross polarization,
      and equilibration by (13)C spin diffusion. The dipolar dephased DQ/SQ spectrum
      shows signals from all linkages between aromatic rings, including a distinctive
      peak from polycondensed aromatics. In EXPANSE NMR, signals of protonated carbons
      are selected in the first spectral dimension by short cross polarization combined
      with dipolar dephasing difference. This removes ambiguities of peak assignment to
      overlapping signals of nonprotonated and protonated aromatic carbons, e.g. near
      125 ppm. Spin diffusion is enhanced by dipolar-assisted rotational resonance.
      Before detection, C-H dipolar dephasing by gated decoupling is applied, which
      selects signals of nonprotonated carbons. Thus, only cross peaks due to
      magnetization originating from protonated C and ending on nearby nonprotonated C
      are retained. Combined with the chemical shifts deduced from the cross-peak
      position, this double spectral editing defines the bonding environment of
      aromatic, COO, and C=O carbons, which is particularly useful for identifying
      furan and arene rings. The C=O carbons, whose chemical shifts vary strongly
      (between 212 and 165 ppm) and systematically depend on their two bonding
      partners, show particularly informative cross peaks, given that one bonding
      partner is defined by the other frequency coordinate of the cross peak. The new
      techniques and the information content of the resulting spectra are validated on
      sulfuric-acid treated low-temperature carbon materials and on products of the
      Maillard reaction. The crucial need for spectral editing for correct peak
      assignment is demonstrated in an example.

PMID- 23871899
TI  - Filter diagonalization method for processing PFG NMR data.
AB  - Obtaining diffusion coefficients from PFG NMR diffusion (a.k.a DOSY) data is, in
      the general case, an ill-posed problem. Numerous methods for processing such data
      have therefore been developed, each with different constraints and assumptions.
      The Regularized Resolvent Transform (RRT) is a proven and robust method for
      spectral inversion. In earlier papers RRT, albeit very slow, was argued to be
      superior for DOSY processing to a related algorithm, the Filter Diagonalization
      Method (FDM). Here FDM is revisited and a new regularization method is
      implemented, which drastically improves the performance and provides spectra of
      comparable or better quality to those provided by RRT. Both the RRT and the FDM
      for DOSY processing have been implemented as options in the free and open source
      DOSY Toolbox. 

PMID- 23871900
TI  - Multivariate data analysis as a PAT tool for early bioprocess development data.
AB  - Early development datasets are typically unstructured, incomplete and truncated,
      yet they are readily available and contain relevant process information which is
      not extracted using classical data analysis techniques. In this paper, we
      illustrate the power of multivariate data analysis (MVDA) as a Process Analytical
      Technology tool to analyze early development data of a PER.C6(r) cell cultivation
      process. MVDA increased our understanding of the process studied. Principal
      component analysis enabled a thorough exploration of the dataset, identifying
      causes for batch deviations and revealing sensitivity of the process to scale.
      These findings were previously undetected using traditional univariate analysis.
      The lack of structure and gaps in the early development datasets made it
      impossible to fit them to more advanced partial least square regression models.
      This paper clearly shows that MVDA should be routinely used to analyze early
      development data to reveal relevant information for later development and scale
      up. The value of these early development runs can be greatly enhanced if the
      experiments are well-structured and accompanied with full process analytics. This
      up-front investment will result in shorter and more efficient process development
      paths, resulting in lower overall development costs for new biopharmaceutical
      products.

PMID- 23871902
TI  - An expedient, ionic liquid mediated multi-component synthesis of novel piperidone
      grafted cholinesterase enzymes inhibitors and their molecular modeling study.
AB  - Series of hitherto unreported piperidone grafted pyridopyrimidines synthesized
      through ionic liquid mediated multi-component reaction. These compounds were
      evaluated for their inhibitory activities against AChE and BChE enzymes. All the
      compounds displayed considerable potency against AChE with IC50 values ranging
      from 0.92 to 9.11 MUM, therein compounds 6a, 6h and 6i displayed superior enzyme
      inhibitory activities compared to standard drug with IC50 values of 0.92, 1.29
      and 2.07 MUM. Remarkably, all the compounds displayed higher BChE inhibitory
      activity compared to galantamine with IC50 values of 1.89-8.13 MUM. Molecular
      modeling, performed for the most active compounds using three dimensional crystal
      structures of TcAChE and hBChE, disclosed binding template of these inhibitors
      into the active site of their respective enzymes. 

PMID- 23871901
TI  - Molecular effects of ER alpha- and beta-selective agonists on regulation of
      energy homeostasis in obese female Wistar rats.
AB  - The molecular mechanisms underlying the effects of selective ER subtype
      activation on lipogenesis, adipogenesis, lipid utilization and storage as well as
      glucose metabolism are currently largely unknown and were analyzed in female OVX
      Wistar rats on a high-fat diet. Rats received estradiol (E2), ER subtype
      selective agonists (Alpha and Beta), and genistein (Gen) for 10 weeks. In adipose
      tissue, treatment with E2, Alpha, and Beta significantly decreased lipogenic
      (SREBP-1c, FAS) and adipogenic genes (LPL, PPAR gamma). In liver and skeletal
      muscle of E2-, Alpha-, Beta-, and Gen-treated animals, lipogenesis and
      triglyceride accumulation were significantly reduced. Increased hepatic and
      muscular PPAR gamma mRNA expression was observed in untreated, Beta- and Gen
      treated animals, which correlates with increased hepatic glucose uptake. However,
      only untreated animals showed impaired insulin sensitivity compared to all other
      groups. Therefore, PPAR gamma up-regulation in untreated animals suggests a
      compensatory mechanism, probably due to increased triglyceride accumulation in
      non-adipose tissues. Beta- and Gen-treated animals may benefit from the anabolic
      potency of ER beta that ameliorates lipid and glucose utilization in muscle.
      Activation of either ER subtype reduces fat enrichment and improves insulin
      sensitivity. Depending on the investigated tissue, different molecular pathways
      seem to be involved.

PMID- 23871903
TI  - Microwave assisted synthesis of some hybrid molecules derived from norfloxacin
      and investigation of their biological activities.
AB  - Norfloxacin was converted to 7-(4-amino-2-fluorophenyl)piperazin derivative (2)
      via the formation of nitro compound. The synthesis of the norfloxacin derivatives
      containing 1,3-thiazole or 1,3-thiazolidin moiety was performed from the reaction
      of 4-chlorophenacylbromide or ethyl bromoacetate with compounds 4-7 obtained
      starting from 2. 3-Fluoro-4-[4-(2-methoxyphenyl)piperazin-1-yl]aniline (14), 5
      {[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-4-phenyl-4H-1,2,4-triazole-3-thiol
      (18) and {[4-(2-methoxy phenyl)piperazin-1-yl]methyl}-1,3,4-oxadiazol-2-thiol
      (19) were obtained starting from 1-(2-methoxyphenyl)piperazine by several steps.
      The treatment of hydrazide (16) with several aldehydes afforded N'-[(2
      hydroxyphenyl)methylen]- (20), N'-[(3-hydroxy-4-methoxy phenyl)methylen]- (21) or
      N'-[1H-indol-3-ylmethylene]-2-[4-(2-methoxyphenyl)piperazin-1-yl]acetohydrazide
      (22). Then, compounds 14, 18, 19 and 22 were condensed with 7-[4
      (chloroacetyl)piperazin-1-yl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3
      carboxylic acid (3) that was obtained from norfloxacine. All newly synthesized
      compounds were screened for their antimicrobial activities and some of them
      exhibited excellent activity. Moreover, one compound was found to have antiurease
      activity. 

PMID- 23871904
TI  - Synthesis and anticancer activity evaluation of a series of [1,2,4]triazolo[1,5
      a]pyridinylpyridines in vitro and in vivo.
AB  - A series of [1,2,4]triazolo[1,5-a]pyridinylpyridines were synthesized and
      characterized. Their antiproliferative activities in vitro were evaluated by MTT
      against three human cancer cell lines including HCT-116, U-87 MG and MCF-7 cell
      lines. The SAR of target compounds was preliminarily discussed. The compounds 1c
      and 2d with potent antiproliferative activities were tested for their effects on
      the AKT and p-AKT(473). The anticancer effect of 1c was evaluated in mice bearing
      sarcoma S-180 model. The results suggest that the title compounds are potent
      anticancer agents. 

PMID- 23871905
TI  - Synthesis of novel analogs of 2-pyrazoline obtained from [(7-chloroquinolin-4
      yl)amino]chalcones and hydrazine as potential antitumor and antimalarial agents.
AB  - A new series of N-acetyl and N-formyl-pyrazoline derivatives 6 and 7-8 were
      synthesized by cyclocondensation reaction of [(7-chloroquinolin-4
      yl)amino]chalcones with hydrazine hydrate in acetic acid and hydrazine hydrate in
      formic acid respectively. These compounds were evaluated in vitro as antitumor
      and as antimalarial agents. Compounds 7b and 8b-e showed remarkable antitumor
      activity against cancer cell lines, with the most important GI50 values ranging
      from 0.13 to 0.99 MUM. The best antimalarial response was observed for compound
      7a with an inhibition percentage of 50.8% for Plasmodium falciparum, a hemolytic
      capacity of 3.2% and an IC50 of 14.1 MUg/mL. 

PMID- 23871906
TI  - Synthesis of thiosemicarbazones derived from N-(4-hippuric acid)thiosemicarbazide
      and different carbonyl compounds as antimicrobial agents.
AB  - New series of thiosemicarbazone derivatives incorporating a hippuric acid moiety
      have been synthesized through the reaction of N-(4-hippuric
      acid)thiosemicarbazide with various carbonyl compounds such as aldehydes, ketones
      and cyclic ketones. The synthesized compounds were tested against bacterial and
      fungal strains. Most of compounds, such as 2-(4-(2-(4
      fluorobenzylidene)hydrazinecarbothioamido)benzamido)acetic acid showed
      significant antibacterial and antifungal activities. These compounds comprise a
      new class of promising broad-spectrum antibacterial and antifungal agents. 

PMID- 23871907
TI  - Discovery and biological evaluation of novel 1,4-benzoquinone and related
      resorcinol derivatives that inhibit 5-lipoxygenase.
AB  - 5-Lipoxygenase (5-LO), an enzyme that catalyzes the initial steps in the
      biosynthesis of pro-inflammatory leukotrienes, is an attractive drug target for
      the pharmacotherapy of inflammatory and allergic diseases. Here, we present the
      discovery and biological evaluation of novel series of 1,4-benzoquinones and
      respective resorcinol derivatives that efficiently inhibit human 5-LO, with
      little effects on other human lipoxygenases. SAR analysis revealed that the
      potency of the compounds strongly depends on structural features of the
      lipophilic residues, where bulky naphthyl or dibenzofuran moieties favor 5-LO
      inhibition. Among the 1,4-benzoquinones, compound Ig 5-[(2-naphthyl)methyl]-2
      hydroxy-2,5-cyclohexadiene-1,4-dione potently blocked 5-LO activity in cell-free
      assays with IC50 = 0.78 MUM, and suppressed 5-LO product synthesis in
      polymorphonuclear leukocytes with IC50 = 2.3 MUM. Molecular docking studies
      suggest a concrete binding site for Ig in 5-LO where select pi-pi interactions
      along with hydrogen bond interactions accomplish binding to the active site of
      the enzyme. Together, our study reveals novel valuable 5-LO inhibitors with
      potential for further preclinical assessment as anti-inflammatory compounds. 

PMID- 23871908
TI  - Modulation of human neutrophils' oxidative burst by flavonoids.
AB  - Inflammation is a normal response towards tissue injury, but may become
      deleterious to the organism if uncontrolled. The overproduction of reactive
      species during the inflammatory process may cause or magnify the damage at
      inflammatory sites. Flavonoids have been suggested as therapeutic agents to avoid
      such damage, as these compounds exhibit anti-inflammatory activity, through the
      modulation of oxidative stress and signalling pathways. Both effects may
      attenuate neutrophils' activities at inflammatory sites. In this study, we
      investigated the structure/activity relationship of a series of flavonoids on the
      oxidative burst of human neutrophils in vitro, as a measure of its anti
      inflammatory potential. Neutrophils were stimulated with phorbol-12-myristate-13
      acetate, and fluorescence and chemiluminescence techniques were used to evaluate
      the generation of reactive oxygen species. All the tested flavonoids revealed the
      ability to modulate the neutrophil's oxidative burst. From the obtained results,
      the pivotal role of the catechol group in the B-ring was evidenced as well as the
      minor importance of the hydroxylations in the A-ring, which did not appear to be
      determinant for the activity, although clearly influencing the lipophilicity of
      the tested flavonoids. It is also clarified the importance of the methylation in
      the OH group at the B-ring catechol moiety. In conclusion, the obtained results
      uncover new possible strategies for the resolution of inflammatory processes,
      using flavonoids to modulate neutrophil's oxidative burst. 

PMID- 23871909
TI  - Design and synthesis of novel quinazoline nitrogen mustard derivatives as
      potential therapeutic agents for cancer.
AB  - Thirteen novel quinazoline nitrogen mustard derivatives were designed,
      synthesized and evaluated for their anticancer activities in vitro and in vivo.
      Cytotoxicity assays were carried out in five cancer cell lines (HepG2, SH-SY5Y,
      DU145, MCF-7 and A549) and one normal human cell line (GES-1), in which compound
      22b showed very low IC50 to HepG2 (the IC50 value is 3.06 MUM), which was lower
      than Sorafenib. Compound 22b could inhibit cell cycle at S and G2/M phase and
      induce cell apoptosis. In the HepG2 xenograft model, 22b exhibited significant
      cancer growth inhibition with low host toxicity in vivo. 

PMID- 23871910
TI  - One-pot microwave assisted synthesis of new 2-alkoxycarbonylmethylene-4-oxo-1,5
      benzo-, naphtho-, and pyridodiazepines and assessment of their cytogenetic
      activity.
AB  - 1,5-Benzo-, naphtho-, and pyridodiazepines 3 have been synthesized in excellent
      yields in one-step from the reaction of o-phenylenediamines with
      acetonedicarboxylates through microwave assisted acid catalysis. In order to
      ascertain their cytogenetic activity in vitro at doses equivalent to the per os
      doses of common 1,4-benzodiazepine drugs, Sister Chromatid Exchanges (SCEs) were
      employed, and for the determination of cytostaticity the Proliferation Rate Index
      (PRI) on lymphocytes of human whole blood cultures was estimated. It was found
      that benzodiazepines 3a, 3c, and 3e exhibit significant cytoprotection, but mild
      cytostatic effect (a statistically significant reduction of SCEs and a confined
      decrease of PRI values at similar concentrations). The most active compound was
      found to be 3e. 

PMID- 23871911
TI  - Synthesis and antiprotozoal activities of benzyl phenyl ether diamidine
      derivatives.
AB  - Sixty-two cationic benzyl phenyl ether derivatives (36 amidines and 26 prodrugs)
      were prepared and assayed for activities in vitro and in vivo against Trypanosoma
      brucei rhodesiense (STIB900), and in vitro against Plasmodium falciparum (K1) and
      Leishmania donovani axenic amastigotes. 3-Amidinobenzyl 4-amidino-2-iodo-6
      methoxyphenyl ether dihydrochloride (55, IC50 = 3.0 nM) and seven other compounds
      exhibited IC50 values below 10 nM against T. b. rhodesiense in vitro. The 2-bromo
      4,4'-diamidino analogue 19 (IC50 = 4.0 nM) and 12 other analogues were more
      potent than pentamidine (IC50 = 46 nM) against P. falciparum. The 3',4-diamidino
      2,6-diiodo analogue 49 (IC50 = 1.4 MUM) and two other compounds were more
      effective than pentamidine (IC50 = 1.8 MUM) against L. donovani. A prodrug, 3',4
      bis(N"-methoxy)amidino-2-bromo derivative 38, was the most efficacious against
      trypanosome infected mice, attaining 4/4 cures in four daily 25 mg/kg oral doses,
      and the 2-chloro-4,4'-diamidine 18 cured 3/4 mice in four daily 5 mg/kg
      intraperitoneal doses. 

PMID- 23871912
TI  - A structure-activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin
      5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and
      associated anti-angiogenic activities.
AB  - Thirty-three 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo
      analogues were designed and synthesized which contained different substituents at
      meta- and/or para-positions of 2-phenyl or 2-benzyl ring attached to the fused
      ring structure. The preliminary pharmacological evaluation demonstrated that the
      5-thioxo analogues of 1,2,4-triazolo[1,5-a][1,3,5]triazine exhibited a varying
      degree of inhibitory activity towards thymidine phosphorylase, comparable or
      better than reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value = 42.63
      MUM). Moreover, compounds 5q and 6i displayed a mixed-type of inhibitory
      mechanism in the presence of variable concentrations of thymidine (dThd). In
      addition, selected compounds were found to have a noticeable inhibitory effect on
      the expression of angiogenesis markers, including VEGF and MMP-9 in MDA-MB-231
      breast cancer cells. 

PMID- 23871913
TI  - Cathepsin D activity and selectivity in the acidic conditions of a tumor
      microenvironment: Utilization in the development of a novel Cathepsin D substrate
      for simultaneous cancer diagnosis and therapy.
AB  - Pro-Cathepsin D (pCD) is an aspartyl endopeptidase which is over expressed in
      many cancers. This over expression generally led to its secretion into the
      extracellular culture medium of cancer cells. Moreover, pCD can auto activate and
      cleave its substrates at an acidic pH compatible with that found in tumor
      microenvironments (TME). Thus, exploiting these two pathological characteristics
      of TME offers the opportunity to develop new protease-activated vector on the
      basis of their specific substrate structures. The aim of this study was to
      validate new pCD substrates in the extracellular pH conditions of TME. As a first
      step, we investigated the effect of pH on the catalytic activity and selectivity
      of mature Cathepsin D (CD). It was found that the increase in the pH of the media
      led to a decrease in the reaction rate. However, the specificity of mature CD was
      not affected by a variation in pH. In the second step, the effect of the
      substrate structure was studied. We demonstrated that the substrate structure had
      a significant effect on the catalytic activity of CD. In fact, some modifications
      in peptide structure induced a change in the catalytic behavior that involved a
      substrate activation phenomenon. We suggest that this activation may be related
      to the amphiphilic nature of the modified peptide that may induce an interfacial
      activation mechanism. Finally, pCD, which is the major form found in the
      extracellular culture medium of cancer cells, was used. We demonstrated that the
      proform of CD cleave the modified peptide 5 at pH 6.5 with the same cleavage
      selectivity obtained with the mature form of the protease. These data provide a
      better understanding of CD behavior in tumor microenvironment conditions and this
      knowledge can be used to develop more specific tools for diagnosis and drug
      delivery.

PMID- 23871914
TI  - Calcein release behavior from liposomal bilayer; influence of
      physicochemical/mechanical/structural properties of lipids.
AB  - The design of the drug delivery depends upon different parameters. One of the
      most noticeable factors in design of the drug delivery is drug-release profile
      which determines the site of action, the concentration of the drug at the time of
      administration, the period of time that the drug must remain at a therapeutic
      concentration. To get a better understanding of drug release, large unilamellar
      liposomes containing calcein were prepared using 1,2-dioleoyl-sn-glycero-3
      phosphocholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1,2
      palmitoyl-sn-glycero-3-phosphocholine, and a mixture of them; calcein was chosen
      as a model of hydrophilic drug. The calcein permeability across liposomal
      membrane (with different compositions) was evaluated on the basis of the first
      order kinetic by spectrofluorometer. Also, the effects of liposome
      composition/fluidity as well as the incubation temperature/pH were investigated.
      Furthermore, we simulated the digestion condition in the gastrointestinal tract
      in humans, to mimic human gastro-duodenal digestion to monitor calcein release
      during the course of the digestion process. In vitro digestion model ''pH stat''
      was used to systematically examine the influence of pH/enzyme on phospholipid
      liposomes digestion under simulated gastro-duodenal digestion. The results
      revealed that calcein permeates across liposomal membrane without membrane
      disruption. The release rate of calcein from the liposomes depends on the number
      and fluidity of bilayers and its mechanical/physical properties such as
      permeability, bending elasticity. Chemo-structural properties of drugs like as
      partition coefficient (Log P), H-bonding, polar surface area (PSA) are also
      determinative parameter in release behavior. Finally, stimulated emission
      depletion (STED) microscopy was used to study calcein translocation through
      liposomal bilayers.

PMID- 23871915
TI  - Triglyceride-rich lipoproteins and cytosolic lipid droplets in enterocytes: key
      players in intestinal physiology and metabolic disorders.
AB  - During the post-prandial phase, intestinal triglyceride-rich lipoproteins (TRL)
      i.e. chylomicrons are the main contributors to the serum lipid level, which is
      linked to coronary artery diseases. Hypertriglyceridemia can originate from
      decreased clearance or increased production of TRL. During lipid absorption,
      enterocytes produce and secrete chylomicrons and transiently store lipid droplets
      (LDs) in the cytosol. The dynamic fluctuation of triglycerides in cytosolic LDs
      suggests that they contribute to TRL production and may thus control the length
      and amplitude of the post-prandial hypertriglyceridemia. In this review, we will
      describe the recent advances in the characterization of enterocytic LDs. The role
      of LDs in chylomicron production and secretion as well as potential previously
      unsuspected functions in the metabolism of vitamins, steroids and prostaglandins
      and in viral infection will also be discussed. 

PMID- 23871916
TI  - A new phylogeny for the genus Picea from plastid, mitochondrial, and nuclear
      sequences.
AB  - Studies over the past ten years have shown that the crown groups of most conifer
      genera are only about 15-25 Ma old. The genus Picea (spruces, Pinaceae), with
      around 35 species, appears to be no exception. In addition, molecular studies of
      co-existing spruce species have demonstrated frequent introgression. Perhaps not
      surprisingly therefore previous phylogenetic studies of species relationships in
      Picea, based mostly on plastid sequences, suffered from poor statistical support.
      We therefore generated mitochondrial, nuclear, and further plastid DNA sequences
      from carefully sourced material, striking a balance between alignability with
      outgroups and phylogenetic signal content. Motif duplications in mitochondrial
      introns were treated as characters in a stochastic Dollo model; molecular clock
      models were calibrated with fossils; and ancestral ranges were inferred under
      maximum likelihood. In agreement with previous findings, Picea diverged from its
      sister clade 180 million years ago (Ma), and the most recent common ancestor of
      today's spruces dates to 28 Ma. Different from previous analyses though, we find
      a large Asian clade, an American clade, and a Eurasian clade. Two expansions
      occurred from Asia to North America and several between Asia and Europe. Chinese
      P. brachytyla, American P. engelmannii, and Norway spruce, P. abies, are not
      monophyletic, and North America has ten, not eight species. Divergence times
      imply that Pleistocene refugia are unlikely to be the full explanation for the
      relationships between the European species and their East Asian relatives. Thus,
      northern Norway spruce may be part of an Asian species complex that diverged from
      the southern Norway spruce lineage in the Upper Miocene, some 6 Ma, which can
      explain the deep genetic gap noted in phylogeographic studies of Norway spruce.
      The large effective population sizes of spruces, and incomplete lineage sorting
      during speciation, mean that the interspecific relationships within each of the
      geographic clades require further studies, especially based on genomic
      information and population genetic data.

PMID- 23871917
TI  - Multilocus molecular phylogeny of Gasteropelecidae (Ostariophysi: Characiformes)
      reveals the existence of an unsuspected diversity.
AB  - The characiform family Gasteropelecidae, the so-called freshwater hatchetfishes,
      is comprised of three genera and nine species found in Panama and all South
      American countries except Chile. Our goal was to investigate the molecular
      characteristics, phylogenetic relationships among the species and genera of
      Gasteropelecidae and phylogenetic relationships between the Gasteropelecidae
      family with other Characiformes. DNA fragments from two mitochondrial (16S rRNA
      and Cytochrome B) and three nuclear genes (Rag1, Rag2 and Myh6) were sequenced.
      Our results corroborate the morphology-based hypothesized monophyly of the
      Gasteropelecidae family and most of the relationships among its genera. However,
      the genus Gasteropelecus is polyphyletic because G. maculatus is placed as the
      sister group to all other gasteropelecids, whereas G. sternicla is more closely
      related to species of Carnegiella. Similarly, the species Carnegiella strigata is
      not monophyletic, which suggests that the family needs a taxonomic review.
      Moreover, the species Thoracocharax stellatus was composed by four distinct
      lineages suggesting the this species may represents a species complex. 

PMID- 23871918
TI  - Unraveling trauma and stress, coping resources, and mental well-being among older
      adults in prison: empirical evidence linking theory and practice.
AB  - PURPOSE OF STUDY: A theoretical integration of the life course perspective,
      cumulative advantage, disadvantage or inequality, and stress processing theories
      provide an important integrated lens to study the relationship between
      accumulated interpersonal, social-structural, and historical trauma and stressful
      experiences on mental well-being mental well-being in later life. DESIGN AND
      METHODS: This study builds upon the extant literature by examining the mediating
      role of coping resources on the relationship between trauma and stressful life
      experiences, post traumatic stress symptoms, and mental well-being among a sample
      of 677 adults aged 50 and older in prison. RESULTS: The majority (70%) reported
      experiencing one or more traumatic or stressful life experiences during their
      life span. Participants also reported on average 11 occurrences of multilevel
      trauma and stressful life events and lingering subjective distress related to
      these events. Results of a structural equation model revealed that internal and
      external coping resources (e.g., cognitive, emotional, physical, spiritual, and
      social) had a significant and inverse effect on the relationship between trauma
      and stressful life experiences and mental well-being. IMPLICATIONS: As prisons
      are forced to deal with an aging population, research in this area can take the
      preliminary steps to enhance understanding of risk and resilience among older
      adults in prison. This understanding will aid in the development and improvement
      of integrated theory-based interventions seeking to increase human rights,
      health, and well-being among older adults in prison.

PMID- 23871919
TI  - Differential expression of cathepsins K, S and V between young and aged Caucasian
      women skin epidermis.
AB  - Cutaneous aging translates drastic structural and functional alterations in the
      extracellular matrix (ECM). Multiple mechanisms are involved, including changes
      in protease levels. We investigated the age-related protein expression and
      activity of cysteine cathepsins and the expression of two endogenous protein
      inhibitors in young and aged Caucasian women skin epidermis. Immunofluorescence
      studies indicate that the expression of cathepsins K, S and V, as well as
      cystatins A and M/E within keratinocytes is reduced in photoprotected skin of
      aged women. Furthermore, the overall endopeptidase activity of cysteine
      cathepsins in epidermis lysates decreased with age. Albeit dermal elastic fiber
      and laminin expression is reduced in aged skin, staining of nidogen-1, a key
      protein in BM assembly that is sensitive to proteolysis by cysteine, metallo- and
      serine proteases, has a similar pattern in both young and aged skin. Since
      cathepsins contribute to the hydrolysis and turnover of ECM/basement membrane
      components, the abnormal protein degradation and deposition during aging process
      may be related in part to a decline of lysosomal/endosomal cathepsin K, S and V
      activity. 

PMID- 23871920
TI  - Thermo-alkaline pretreatment of waste activated sludge at low-temperatures:
      effects on sludge disintegration, methane production, and methanogen community
      structure.
AB  - Low-temperature thermo-alkaline pretreatment of waste activated sludge (WAS) was
      studied, within the region of 0-0.2 M NaOH and 60-90 degrees C, for the effects
      of NaOH concentration and temperature on sludge degradability in anaerobic
      digestion (AD). Significant disintegration of sludge solids (up to 75.6%) and an
      increase in methane production (up to 70.6%) were observed in the pretreatment
      trials. Two quadratic models were successfully generated by response surface
      analysis (R(2)>0.9, p<0.05) to approximate how the degree of sludge
      disintegration (SD) and methane production (MP) respond to changes in the
      pretreatment conditions. The maximum responses of SD (77.8%) and MP (73.9%
      increase over the control) were shown at [0.16 M NaOH, 90 degrees C] and [0.10 M
      NaOH, 73.7 degrees C], respectively. NaOH addition showed a significant influence
      on the evolution of methanogen community structure during AD, whereas temperature
      did not. Aceticlastic Methanosaeta and Methanosarcina speceies were likely the
      major methanogens.

PMID- 23871921
TI  - Calibration of hydrodynamic behavior and biokinetics for TOC removal modeling in
      biofilm reactors under different hydraulic conditions.
AB  - In this study, total organic carbon (TOC) biodegradation was simulated by GPS-X
      software in biofilm reactors with carriers of plastic rings and glass beads under
      different hydraulic conditions. Hydrodynamic model by retention time distribution
      and biokinetic measurement by in-situ batch test served as two significant parts
      of model calibration. Experimental results showed that TOC removal efficiency was
      stable in both media due to the enough height of column, although the actual
      hydraulic volume changed during the variation of hydraulic condition. Simulated
      TOC removal efficiencies were close to experimental ones with low theil
      inequality coefficient values (below 0.15). Compared with glass beads, more TOC
      was removed in the filter with plastic rings due to the larger actual hydraulic
      volume and lower half saturation coefficient in spite of its lower maximum
      specific growth rate of biofilm, which highlighted the importance of calibrating
      hydrodynamic behavior and biokinetics. 

PMID- 23871922
TI  - Pretreatment of sugarcane bagasse with liquid hot water and aqueous ammonia.
AB  - Low water consumption operation (LWCO) can reduce the usage of water and energy
      input for the liquid hot water (LHW) pretreatment of sugarcane bagasse (SB) but
      causes great negative effects on the saccharification rate of xylose and
      enzymatic digestibility (ED) of cellulose. Therefore, a combined pretreatment
      with LHW and aqueous ammonia (LHWAA) was developed. ED of glucan and xylan is
      enhanced greatly resulted from the removal of hemicellulose and lignin after the
      LHWAA pretreatment. However, the intriguing results of low lignin removal and ED
      value were observed at the high reaction temperature of 180 degrees C for the
      second step pretreatment of AA. It was proposed that lignin or pseudo-lignin
      droplet redeposited on the surface of residual solids might play a crucial role
      in determining the ED, so it is indispensable to make the enzyme access to the
      cellulose by the step of post-treatment with ultrasonic washing or hot washing.
      Coupled with the process of post-treatment and enzymatic hydrolysis, a high
      hemicellulose derived sugars recovery of 75.5% and glucose recovery of 87% was
      obtained for LHWAA pretreatment. 

PMID- 23871923
TI  - Biotransformation of benzimidazole anthelmintics in reed (Phragmites australis)
      as a potential tool for their detoxification in environment.
AB  - Benzimidazole anthelmintics, the drugs against parasitic worms, are widely used
      in human as well as veterinary medicine. Following excretion, these substances
      may persist in the environment and impact non-target organisms. In order to test
      phytoremediation as a possible tool for detoxification of anthelmintics in
      environment, the biotransformation pathways of albendazole (ABZ) and flubendazole
      (FLU) were studied in reed (Phragmites australis) in vitro. Reed cells were able
      to uptake and biotransform both anthelmintics. Ten ABZ metabolites and five FLU
      metabolites were found. Some atypical biotransformation reactions (formation of
      glucosylglucosides, acetylglucosides and xylosylglucosides), which have not been
      described previously, were identified. Based on the obtained results, the schemes
      of metabolic pathways of ABZ and FLU in reed were proposed. Most of ABZ and FLU
      metabolites can be considered as anthelmintically less active; therefore uptake
      and biotransformation of these anthelmintics by reed could be useful for decrease
      of their toxicity in environment. 

PMID- 23871924
TI  - Effect of temperature on continuous fermentative hydrogen production from
      Laminaria japonica by anaerobic mixed cultures.
AB  - The temperature effect on continuous dark fermentative hydrogen production from
      non-pretreated Laminaria japonica was investigated in the present study. In a
      preliminary step, the fermentors were continuously operated as an inoculation
      process at three different temperatures, 35, 50 and 65 degrees C, to respectively
      represent mesophilic, thermophilic, and hyperthermophilic conditions. An
      optimization process was subsequently conducted with a range of organic loading
      rate (OLR) and cultivation pH. Among the various operation conditions, the
      maximum H2 yield, 61.3+/-2.0 mL H2/g TS, was observed under a mesophilic
      condition at OLR of 3.4 g COD/L/d and pH 5.5. From a PCR-DGGE analysis, it was
      found that an increase of temperature can reduce the microbial diversity and
      change the predominant species. Finally, total cellulase activity was measured,
      to investigate the effect of temperature on hydrolysis of L. japonica. The
      highest cellulase activity was 0.19+/-0.02 FPU/mL, observed at 35 degrees C,
      coinciding with the maximum H2 yield.

PMID- 23871925
TI  - Specific effects of fiber size and fiber swelling on biomass substrate surface
      area and enzymatic digestibility.
AB  - To clarify the specific effect of biomass substrate surface area on its enzymatic
      digestibility, factors of fiber size reduction and swelling changes were
      investigated by using poplar substrates with controlled morphological and
      chemical properties after modified chemical pulping. Results showed that fiber
      size changes had insignificant influence on enzymatic hydrolysis, although the
      external surface area increased up to 41% with the reduction of fiber size.
      Swelling changes caused by increased biomass fiber porosities after PFI refining
      showed a significant influence on the efficiency of enzymatic hydrolysis. It is
      also found that chemical properties such as xylan and lignin content can
      influence the swelling effect. Xylan is confirmed to facilitate substrate
      hydrolysability by swelling, while lignin restricts swelling effect and thus
      minimizes the enzyme accessibility to substrates. 

PMID- 23871926
TI  - Microwave pyrolysis of microalgae for high syngas production.
AB  - The microwave induced pyrolysis of the microalgae Scenedesmus almeriensis and its
      extraction residue was carried out at 400 and 800 degrees C. The results show
      that it is possible to obtain a gas fraction with a high content (c.a. 50vol.%)
      in H2 from both materials, regardless of the pyrolysis temperature. Furthermore,
      an outstanding syngas production and high gas yields were achieved. The maximum
      syngas concentration obtained was c.a. 94 vol.%, in the case of the pyrolysis of
      the residue at 800 degrees C, indicating that the production of CO2 and light
      hydrocarbons was minimized. The same experiments were carried out in a
      conventional electric furnace in order to compare the products and yields
      obtained. It was found that microwave induced pyrolysis gives rise not only to
      higher gas yields but also to greater syngas and H2 production.

PMID- 23871927
TI  - The fate of pharmaceuticals, steroid hormones, phytoestrogens, UV-filters and
      pesticides during MBR treatment.
AB  - This study examined the relationship between molecular properties and the fate of
      trace organic contaminants (TrOCs) in the aqueous and solid phases during
      wastewater treatment by MBR. A set of 29 TrOCs was selected to represent
      pharmaceuticals, steroid hormones, phytoestrogens, UV-filters and pesticides that
      occur ubiquitously in municipal wastewater. Both adsorption and
      biodegradation/transformation were found responsible for the removal of TrOCs by
      MBR treatment. A connection between biodegradation and molecular structure could
      be observed while adsorption was the dominant removal mechanism for the
      hydrophobic (logD>3.2) compounds. Highly hydrophobic (logD>3.2) but readily
      biodegradable compounds did not accumulate in sludge. In contrast, recalcitrant
      compounds with a moderate hydrophobicity, such as carbamazepine, accumulated
      significantly in the solid phase. The results provide a framework to predict the
      removal and fate of TrOCs by MBR treatment. 

PMID- 23871928
TI  - Fewer augments with fewer complications--laudable, but likely?

PMID- 23871929
TI  - Primary bladder exstrophy closure in neonates: challenging the traditions.
AB  - PURPOSE: We describe a novel approach to neonatal bladder exstrophy closure that
      challenges the role of postoperative immobilization and pelvic osteotomy.
      MATERIALS AND METHODS: We reviewed the primary management of bladder exstrophy at
      our institutions between 2007 and 2011. In particular we compared postoperative
      management in the surgical ward using epidural analgesia to muscle paralysis and
      ventilation in the intensive care unit. Clinical outcome measures were time to
      full feed, length of stay, postoperative complications and redo closure. Cost
      effectiveness was also evaluated using hospital financial data. Data are
      expressed as median (range). Significance was explored by Fisher exact test and
      unpaired t-test. RESULTS: A total of 74 patients underwent primary closure
      without osteotomy. Successful closure was achieved in 70 patients (95%). A total
      of 48 cases (65%) were managed on the ward (group A) and 26 (35%) were
      transferred to the intensive care unit (group B). The 2 groups were homogeneous
      for gestational age (median 39 weeks, range 27 to 41) and age at closure (3 days,
      1 to 152). Complications requiring surgical treatment were noted in 4 patients
      (8.3%) in group A and 3 (11.5%) in group B (p = 0.609). Length of stay was
      significantly shorter for the group managed on the ward (11 vs 18 days, p
      <0.0001). Median costs were $42,732 for patients admitted to the intensive care
      unit and $16,214 for those admitted directly to the surgical ward (p <0.0001).
      CONCLUSIONS: Primary closure of bladder exstrophy without lower limb
      immobilization and osteotomy is feasible. Postoperative care on the surgical ward
      using epidural analgesia results in shorter hospitalization.

PMID- 23871930
TI  - Bladder lipoma.

PMID- 23871931
TI  - What is the role of cost-effectiveness analysis in clinical practice?

PMID- 23871932
TI  - Elucidation of phosphodiesterase type 5 inhibitor mechanism of action.

PMID- 23871933
TI  - Spatial distribution of phagolysosomes is independent of the regulation of
      lysosome position by Rab34.
AB  - Within a cell, the regulation of organelle positioning is considered to be
      critical in spatio-temporal responses. The position of late endocytic organelles
      (named here lysosomes for simplicity) is tightly controlled and has a functional
      impact on processes like endocytosis, phagocytosis and autophagocytosis. The
      cytoplasmic distribution profile of lysosomes can be easily determined in cells
      where the cytoplasm/nuclear ratio in a cross-section area is high. However,
      determining lysosomal position in cells with lower cytoplasm/nuclear ratio, such
      as macrophages is more challenging. Here, we describe a method that can be
      efficiently and accurately used to determine the position of organelles in
      macrophages using confocal microscopy in two-dimensional (2D) images. Using this
      approach in macrophages, we confirmed previous observations in epithelial cells
      that both changes in cytoplasmic pH and the levels of active Rab34 induced a re
      distribution of lysosomes to the cell centre or periphery. Noteworthy is that
      this Rab34-dependent re-distribution of lysosomes did not significantly affect
      the spatial distribution profile of phagolysosomes in the cytoplasm. We conclude
      that although Rab34 regulates both lysosomal positioning and lysosome to
      phagosome fusion, the latter effect is not due to the regulation of the
      cytoplasmic accessibility of lysosomes to phagosomes by Rab34. 

PMID- 23871934
TI  - The self-renewal of mouse embryonic stem cells is regulated by cell-substratum
      adhesion and cell spreading.
AB  - Mouse embryonic stem cells (mESCs) undergo self-renewal in the presence of the
      cytokine, leukaemia inhibitory factor (LIF). Following LIF withdrawal, mESCs
      differentiate, and this is accompanied by an increase in cell-substratum adhesion
      and cell spreading. The purpose of this study was to investigate the relationship
      between cell spreading and mESC differentiation. Using E14 and R1 mESC lines, we
      have restricted cell spreading in the absence of LIF by either culturing mESCs on
      chemically defined, weakly adhesive biomaterial substrates, or by manipulating
      the cytoskeleton. We demonstrate that by restricting the degree of spreading by
      either method, mESCs can be maintained in an undifferentiated and pluripotent
      state. Under these conditions, self-renewal occurs without the need for LIF and
      is independent of nuclear translocation of tyrosine-phosphorylated STAT3 or beta
      catenin, which have previously been implicated in self-renewal. We also
      demonstrate that the effect of restricted cell spreading on mESC self-renewal is
      not mediated by increased intercellular adhesion, as evidenced by the
      observations that inhibition of mESC adhesion using a function blocking anti E
      cadherin antibody or siRNA do not promote differentiation. These results show
      that mESC spreading and differentiation are regulated both by LIF and by cell
      substratum adhesion, consistent with the hypothesis that cell spreading is the
      common intermediate step in the regulation of mESC differentiation by either LIF
      or cell-substratum adhesion. 

PMID- 23871935
TI  - Genistein modulates oxidative stress in breast cancer cell lines according to
      ERalpha/ERbeta ratio: effects on mitochondrial functionality, sirtuins,
      uncoupling protein 2 and antioxidant enzymes.
AB  - Genistein is a biologically active isoflavone with estrogenic activity and can be
      found in a variety of soy products. This natural compound displays a wide array
      of biological activities, but it is best known for its ability to inhibit cancer
      progression, especially for hormone-related ones such as breast cancer. Genistein
      has been shown to bind both the estrogen receptor alpha (ERalpha) and the
      estrogen receptor beta (ERbeta), although it has a higher affinity for the
      ERbeta. The ERalpha/ERbeta ratio is a prognostic marker for breast tumors, and
      ERbeta expression could indicate the presence of tumors more benign in state,
      whereas ERalpha indicates malignant tumors. The objective of the present study
      was to investigate the effects of genistein on oxidative stress and mitochondrial
      functionality through its interaction with the estrogen receptor in breast cancer
      cell lines with different ERalpha/ERbeta ratios. The lower ERalpha/ERbeta ratio
      T47D cell line showed lower oxidative stress and greater mitochondrial
      functionality, along with an up-regulation of uncoupling protein 2 and sirtuins.
      On the other hand, genistein-treated MCF-7 cell line, with the highest
      ERalpha/ERbeta ratio, reported no changes for the control situation. On the
      whole, our results show different genistein effects depending on ERalpha/ERbeta
      ratio for oxidative stress regulation, mitochondrial functionality, and
      modulation of UCPs, antioxidant enzymes and sirtuins in breast cancer cell lines.
      Effects of genistein on oxidative stress and mitochondria could be due at least
      in part, to a higher ERbeta presence, but could also be due to up-regulation of
      ERbeta caused by the genistein treatment. 

PMID- 23871936
TI  - Bystander senescence in human peritoneal mesothelium and fibroblasts is related
      to thrombospondin-1-dependent activation of transforming growth factor-beta1.
AB  - Senescence bystander effect refers to a phenomenon in which senescent cells
      elicit the development of senescence phenotype in their nearby young
      counterparts. In this paper we examined the mechanism of senescence bystander
      effect triggered by senescent human peritoneal mesothelial cells (HPMCs) in
      proliferating HPMCs and peritoneal fibroblasts (HPFBs). The results showed that
      conditioned medium (CM) derived from senescent HPMCs elicited a senescence
      response (growth inhibition coupled with increased expression of senescence
      associated beta-galactosidase and accumulation of histone gamma-H2A.X) in either
      early-passage HPMCs or HPFBs. Samples of CM from senescent HPMCs contained
      increased amounts of numerous soluble mediators of which only transforming growth
      factor-beta1 (TGF-beta1) was able to induce senescence phenotype in the both
      types of peritoneal cells, likely through an induction of reactive oxygen species
      (ROS) and p38 mitogen-activated protein kinase (MAPK). At the same time,
      senescent HPMCs released increased amounts of thrombospondin-1 (TSP-1), a major
      activator of TGF-beta1. Significantly, TSP-1 itself was unable to induce
      senescence phenotype in HPMCs or in HPFBs. The experiments employing anti-TSP-1
      antibodies and specific TSP-1 blocking peptide revealed that neutralization of
      TSP-1 in CM prevented TGF-beta1-dependent development of senescence phenotype.
      Collectively, our findings indicate that senescent HPMCs exhibit senescence
      promoting activity toward neighboring young cells (HPMCs and HPFBs), and this
      effect is, at least partly, related to TSP-1-dependent activation and further ROS
      and p38 MAPK-related activity of TGF-beta1. 

PMID- 23871938
TI  - Evidence for water-mediated triplet-triplet energy transfer in the
      photoprotective site of the peridinin-chlorophyll a-protein.
AB  - Experimental and theoretical studies indicate that water molecules between redox
      partners can significantly affect their electron-transfer and possibly also the
      triplet-triplet energy transfer (TTET) properties when in the vicinity of
      chromophores. In the present work, the interaction of an intervening water
      molecule with the peridinin triplet state in the peridinin-chlorophyll a-protein
      (PCP) from Amphidinium carterae is studied by using orientation selective (2)H
      electron spin echo envelope modulation (ESEEM) spectroscopy, in conjunction with
      quantum mechanical calculations. This water molecule is located at the interface
      between the chlorophyll and peridinin pigments involved in the photoprotection
      mechanism (Chl601(602)-Per614(624), for nomenclature see reference [1]), based on
      TTET. The characteristic deuterium modulation pattern is observed in the electron
      spin-echo envelopes for the PCP complex exchanged against (2)H2O. Simulations of
      the time- and frequency-domain two-pulse and three-pulse ESEEM require two types
      of coupled (2)H. The more strongly coupled (2)H has an isotropic coupling
      constant (aiso) of -0.4MHz. This Fermi contact contribution for one of the two
      water protons and the precise geometry of the water molecule at the interface
      between the chlorophyll and peridinin pigments, resulting from the analysis,
      provide experimental evidence for direct involvement of this structured water
      molecule in the mechanism of TTET. The PCP antenna, characterised by a unity
      efficiency of the process, represents a model for future investigations on
      protein- and solvent-mediated TTET in the field of natural/artificial
      photosynthesis. 

PMID- 23871939
TI  - Currently used pesticides and their mixtures affect the function of sex hormone
      receptors and aromatase enzyme activity.
AB  - The endocrine-disrupting potential of pesticides is of health concern, since they
      are found ubiquitously in the environment and in food items. We investigated in
      vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity,
      and aromatase enzyme activity, of the following pesticides: 2-methyl-4
      chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium,
      mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol,
      propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate,
      malathion and the metabolite ethylene thiourea (ETU). The pesticides were
      analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR
      function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO
      K1 cells, respectively, using luciferase reporter gene assays. Effects on
      aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells,
      employing the classical [(3)H](2)O method. Five pesticides (terbuthylazine,
      propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER
      transactivity, and three pesticides (bitertanol, propiconazole and mancozeb)
      antagonized the AR activity in a concentration-dependent manner. Three pesticides
      (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase
      activity. In addition, two mixtures, consisting of three pesticides (bitertanol,
      propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol,
      propiconazole, cypermethrin, malathion), respectively, induced the ER
      transactivity and aromatase activity, and additively antagonized the AR
      transactivity. In conclusion, our data suggest that currently used pesticides
      possess endocrine-disrupting potential in vitro which can be mediated via ER, AR
      and aromatase activities. The observed mixture effects emphasize the importance
      of considering the combined action of pesticides in order to assure proper
      estimations of related health effect risks.

PMID- 23871940
TI  - The influence of collagen and hyaluronan matrices on the delivery and bioactivity
      of bone morphogenetic protein-2 and ectopic bone formation.
AB  - Bone morphogenetic protein-2 (BMP-2) is known to enhance fracture healing when
      delivered via a bovine collagen sponge. However, collagen rapidly releases BMP-2
      with a high burst phase that is followed by a low sustained phase. As a result,
      supra-physiological doses of BMP-2 are often required to successfully treat bone
      defects. High BMP-2 dosing can introduce serious side effects that include edema,
      bone overgrowth, cyst-like bone formation and significant inflammation. As the
      release behavior of BMP-2 carriers significantly affects the efficacy of fracture
      healing, we sought to compare the influence of two BMP-2 delivery matrices with
      contrasting release profiles on BMP-2 bioactivity and ectopic bone formation. We
      compared a thiol-modified hyaluronan (GlycosilTM) hydrogel that exhibits a low
      burst followed by a sustained release of BMP-2 to a collagen sponge for the
      delivery of three different doses of BMP-2, the bioactivities of released BMP-2
      and ectopic bone formation. Analysis of bone formation by micro-computed
      tomography revealed that low burst followed by sustained release of BMP-2 from a
      hyaluronan hydrogel induced up to 456% more bone compared to a BMP-2 dose-matched
      collagen sponge that has a high burst and sustained release. This study
      demonstrates that BMP-2 released with a low burst followed by a sustained release
      of BMP-2 is more desirable for bone formation. This highlights the therapeutic
      potential of hydrogels, particularly hyaluronan-based, for the delivery of BMP-2
      for the treatment of bone defects and may help abrogate the adverse clinical
      effects associated with high dose growth factor use. 

PMID- 23871937
TI  - Evolution of cytochrome bc complexes: from membrane-anchored dehydrogenases of
      ancient bacteria to triggers of apoptosis in vertebrates.
AB  - This review traces the evolution of the cytochrome bc complexes from their early
      spread among prokaryotic lineages and up to the mitochondrial cytochrome bc1
      complex (complex III) and its role in apoptosis. The results of phylogenomic
      analysis suggest that the bacterial cytochrome b6f-type complexes with short
      cytochromes b were the ancient form that preceded in evolution the cytochrome bc1
      type complexes with long cytochromes b. The common ancestor of the b6f-type and
      the bc1-type complexes probably resembled the b6f-type complexes found in
      Heliobacteriaceae and in some Planctomycetes. Lateral transfers of cytochrome bc
      operons could account for the several instances of acquisition of different types
      of bacterial cytochrome bc complexes by archaea. The gradual oxygenation of the
      atmosphere could be the key evolutionary factor that has driven further
      divergence and spread of the cytochrome bc complexes. On the one hand, oxygen
      could be used as a very efficient terminal electron acceptor. On the other hand,
      auto-oxidation of the components of the bc complex results in the generation of
      reactive oxygen species (ROS), which necessitated diverse adaptations of the b6f
      type and bc1-type complexes, as well as other, functionally coupled proteins. A
      detailed scenario of the gradual involvement of the cardiolipin-containing
      mitochondrial cytochrome bc1 complex into the intrinsic apoptotic pathway is
      proposed, where the functioning of the complex as an apoptotic trigger is viewed
      as a way to accelerate the elimination of the cells with irreparably damaged, ROS
      producing mitochondria. This article is part of a Special Issue entitled:
      Respiratory complex III and related bc complexes. 

PMID- 23871942
TI  - Glycosaminoglycan mimetic peptide nanofibers promote mineralization by osteogenic
      cells.
AB  - Bone tissue regeneration is accomplished by concerted regulation of protein-based
      extracellular matrix components, glycosaminoglycans (GAGs) and inductive growth
      factors. GAGs constitute a significant portion of the extracellular matrix and
      have a significant impact on regulating cellular behavior, either directly or
      through encapsulation and presentation of growth factors to the cells. In this
      study we utilized a supramolecular peptide nanofiber system that can emulate both
      the nanofibrous architecture of collagenous extracellular matrix and the major
      chemical composition found on GAGs. GAGs and collagen mimetic peptide nanofibers
      were designed and synthesized with sulfonate and carboxylate groups on the
      peptide scaffold. The GAG mimetic peptide nanofibers interact with bone
      morphogenetic protein-2 (BMP-2), which is a critical growth factor for osteogenic
      activity. The GAG mimicking ability of the peptide nanofibers and their
      interaction with BMP-2 promoted osteogenic activity and mineralization by
      osteoblastic cells. Alkaline phosphatase activity, Alizarin red staining and
      energy dispersive X-ray analysis spectroscopy indicated the efficacy of the
      peptide nanofibers in inducing mineralization. The multifunctional and bioactive
      microenvironment presented here provides osteoblastic cells with osteogenic
      stimuli similar to those observed in native bone tissue. 

PMID- 23871941
TI  - SiO2 and ZnO dopants in three-dimensionally printed tricalcium phosphate bone
      tissue engineering scaffolds enhance osteogenesis and angiogenesis in vivo.
AB  - Calcium phosphate (CaP) scaffolds with three-dimensionally-interconnected pores
      play an important role in mechanical interlocking and biological fixation in bone
      implant applications. CaPs alone, however, are only osteoconductive (able to
      guide bone growth). Much attention has been given to the incorporation of
      biologics and pharmacologics to add osteoinductive (able to cause new bone
      growth) properties to CaP materials. Because biologics and pharmacologics are
      generally delicate compounds and also subject to increased regulatory scrutiny,
      there is a need to investigate alternative methods to introduce osteoinductivity
      to CaP materials. In this study silica (SiO2) and zinc oxide (ZnO) have been
      incorporated into three-dimensional printed beta-tricalcium phosphate (beta-TCP)
      scaffolds to investigate their potential to trigger osteoinduction in vivo.
      Silicon and zinc are trace elements that are common in bone and have also been
      shown to have many beneficial properties, from increased bone regeneration to
      angiogenesis. Implants were placed in bicortical femur defects introduced to a
      murine model for up to 16 weeks. The addition of dopants into TCP increased the
      capacity for new early bone formation by modulating collagen I production and
      osteocalcin production. Neovascularization was found to be up to three times more
      than the pure TCP control group. The findings from this study indicate that the
      combination of SiO2 and ZnO dopants in TCP may be a viable alternative to
      introducing osteoinductive properties to CaPs.

PMID- 23871943
TI  - Direct synthesis of heparin-like poly(ether sulfone) polymer and its blood
      compatibility.
AB  - In this study, heparin-like poly(ethersulfone) (HLPES) was synthesized by a
      combination of polycondensation and post-carboxylation methods, and was
      characterized by Fourier transform infrared spectroscopy, nuclear magnetic
      resonance hydrogen spectrum and gel permeation chromatography. Owing to the
      similar backbone structure, the synthesized HLPES could be directly blended with
      pristine PES at any ratios to prepare PES/HLPES membranes. After the introduction
      of HLPES, the microscopic structure of the modified PES membranes was changed,
      while the hydrophilicity was significantly enhanced. Bovine serum albumin and
      bovine serum fibrinogen adsorption, activated partial thromboplastin time, thromb
      time and platelet adhesion for the modified PES membranes were investigated. The
      results indicated that the blood compatibility of the PES/HLPES membranes was
      significantly improved compared with that of pristine PES membrane. For the
      PES/HLPES membranes, obvious decreases in platelet activation on PF-4 level, in
      complement activation on C3a and C5a levels, and in leukocytes activation on
      CD11b levels were observed compared with those for the pristine PES membrane. The
      improved blood compatibility of the PES/HLPES membrane might due to the existence
      of the hydrophilic groups (-SO3Na, -COONa). Furthermore, the modified PES
      membranes showed good cytocompatibility. Hepatocytes cultured on the PES/HLPES
      membranes presented improved growth in terms of SEM observation, MTT assay and
      confocal laser scanning microscope observation compared with those on the
      pristine PES membrane. These results indicate that the PES/HLPES membranes
      present great potential in blood-contact fields such as hemodialysis and bio
      artificial liver supports. 

PMID- 23871944
TI  - Mechanical, biological and structural characterization of in vitro ruptured human
      carotid plaque tissue.
AB  - Recent experimental studies performed on human carotid plaques have focused on
      mechanical characterization for the purpose of developing material models for
      finite-element analysis without quantifying the tissue composition or relating
      mechanical behaviour to preoperative classification. This study characterizes the
      mechanical and biological properties of 25 human carotid plaques and also
      investigates the common features that lead to plaque rupture during mechanical
      testing by performing circumferential uniaxial tests, Fourier transform infrared
      (FTIR) and scanning electron microscopy (SEM) on each specimen to relate plaque
      composition to mechanical behaviour. Mechanical results revealed large variations
      between plaque specimen behaviour with no correlation to preoperative ultrasound
      prediction. However, FTIR classification demonstrated a statistically significant
      relationship between stress and stretch values at rupture and the level of
      calcification (P=0.002 and P=0.009). Energy-dispersive X-ray spectroscopy was
      carried out to confirm that the calcium levels observed using FTIR analysis were
      accurate. This work demonstrates the potential of FTIR as an alternative method
      to ultrasound forpredicting plaque mechanical behaviour. SEM imaging at the
      rupture sites of each specimen highlighted voids created by the nodes of
      calcifications in the tissue structure which could lead to increased
      vulnerability of the plaque. 

PMID- 23871945
TI  - A system for characterizing Mg corrosion in aqueous solutions using
      electrochemical sensors and impedance spectroscopy.
AB  - Understanding Mg corrosion is important to the development of biomedical implants
      made from Mg alloys. Mg corrodes readily in aqueous environments, producing H2,
      OH- and Mg2+. The rate of formation of these corrosion products is especially
      important in biomedical applications where they can affect cells and tissue near
      the implant. We have developed a corrosion characterization system (CCS) that
      allows realtime monitoring of the solution soluble corrosion products OH-, Mg2+,
      and H2 during immersion tests commonly used to study the corrosion of Mg
      materials. Instrumentation was developed to allow the system to also record
      electrochemical impedance spectra simultaneously in the same solution to monitor
      changes in the Mg samples. We demonstrated application of the CCS by observing
      the corrosion of Mg (99.9%) in three different corrosion solutions: NaCl, HEPES
      buffer, and HEPES buffer with NaCl at 37 degrees C for 48 h. The solution
      concentrations of the corrosion products measured by sensors correlated with the
      results using standard weight loss measurements to obtain corrosion rates. This
      novel approach gives a better understanding of the dynamics of the corrosion
      process in realtime during immersion tests, rather than just providing a
      corrosion rate at the end of the test, and goes well beyond the immersion tests
      that are commonly used to study the corrosion of Mg materials. The system has the
      potential to be useful in systematically testing and comparing the corrosion
      behavior of different Mg alloys, as well as protective coatings.

PMID- 23871946
TI  - SIRT1 gene polymorphisms are associated with growth traits in Nanyang cattle.
AB  - Growth is under complex genetic control and uncovering the molecular mechanisms
      how the genes and polymorphisms affect economic growth traits, are important for
      successful marker-assisted selection and more efficient management strategies in
      commercial cattle populations. SIRT1 is a NAD(+)-dependent deacetylase that
      belongs to the class III histone deacetylases. It plays an important role in
      numerous fundamental cellular processes including gene silencing, DNA repair, and
      metabolic regulation. In addition, SIRT1 acts as an inhibitor of adipogenesis and
      has been associated with body weight regulation. The objective of the present
      study was to identify single nucleotide polymorphisms (SNPs) of bovine SIRT1
      using 1255 animals representing the five main Chinese breeds and to determine if
      these SNPs are associated with economically important traits in Nanyang cattle.
      The approach consisted of resequencing SIRT1 using a panel of DNA from unrelated
      animals of five different breeds and the process revealed five novel SNPs. SNPs
      g.17324T>C and g.17491G>A exhibited a high degree of linkage disequilibrium in
      all tested breeds. Seven major haplotypes accounting for 91.2% of the alleles
      were observed and the haplotype 'GCCGA' was the most common haplotype in NY, QC,
      LX and JX breeds. An association analysis was performed between the five SNPs and
      six performance traits. SNP g.-274C>G was demonstrated to have a strong effect on
      24-months-old body weight and g.17379A>G polymorphism was related to 6 and 12
      months-old body weight in NY population, although these effects did not remained
      significant after the Bonferroni correction. Our results provide evidence that
      polymorphisms in SIRT1 are associated with growth efficiency traits, and may be
      used for marker-assisted selection and management in feedlot cattle.

PMID- 23871947
TI  - Genetic variant in APE1 gene promoter contributes to cervical cancer risk.
AB  - OBJECTIVE: Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in
      the base excision repair pathway, which plays an important role in repairing DNA
      damage caused by oxidation and alkylation. However, the exact mechanism of APE1
      associated with cervical cancer risk is still unknown. In this study, we explored
      whether the APE1 -656T>G polymorphism contributed to the risk of cervical cancer.
      STUDY DESIGN: In the hospital-based case-control study, 306 cervical cancer cases
      and 306 cancer-free controls were genotyped for the APE1 -656T>G polymorphism
      using the polymerase chain reaction restriction fragment length polymorphism
      method. Luciferase reporter assay and electrophoretic mobility shift assay were
      used to evaluate the APE1 transcriptional activity and the binding ability of
      transcriptional factors to the APE1 promoter, respectively. RESULTS: Logistic
      regression analysis showed that individuals with the APE1 -656 TG/GG genotypes
      had a significantly reduced risk of cervical cancer compared with the TT genotype
      (adjusted odds ratio, 0.61; 95% confidence interval, 0.42-0.89). The luciferase
      assays in 3 cell lines showed that the APE1 -656T>G substitution can increase the
      expression of APE1, which was consistent with the finding of association study.
      Electrophoretic mobility shift assay further indicated that the APE1 -656T>G
      polymorphism enhanced the binding affinity of transcriptional factors to the
      promoter region. CONCLUSION: These findings suggested that the APE1 -656T>G
      polymorphism was associated with cervical cancer risk in a Chinese population by
      affecting the binding affinity of transcriptional factors to the promoter,
      leading to an increased expression level of APE1.

PMID- 23871948
TI  - A randomized trial comparing conventional and robotically assisted total
      laparoscopic hysterectomy.

PMID- 23871949
TI  - Reply: To PMID 23395927.

PMID- 23871950
TI  - Incidence, risk factors, and temporal trends in severe postpartum hemorrhage.
AB  - OBJECTIVE: Because the diagnosis of postpartum hemorrhage (PPH) depends on the
      accoucheur's subjective estimate of blood loss and varies according to mode of
      delivery, we examined temporal trends in severe PPH, defined as PPH plus receipt
      of a blood transfusion, hysterectomy, and/or surgical repair of the uterus. STUDY
      DESIGN: We analyzed 8.5 million hospital deliveries in the US Nationwide
      Inpatient Sample from 1999 to 2008 for temporal trends in, and risk factors for,
      severe PPH, based on International Classification of Diseases, 9th revision,
      clinical modification diagnosis and procedure codes. Sequential logistic
      regression models that account for the stratified random sampling design were
      used to assess the extent to which changes in risk factors explain the trend in
      severe PPH. RESULTS: Of the total 8,571,209 deliveries, 25,906 (3.0 per 1000)
      were complicated by severe PPH. The rate rose from 1.9 to 4.2 per 1000 from 1999
      to 2008 (P for yearly trend < .0001), with increases in severe atonic and
      nonatonic PPH, due especially to PPH with transfusion, but also PPH with
      hysterectomy. Significant risk factors included maternal age >=35 years (adjusted
      odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.5-1.6), multiple pregnancy
      (aOR, 2.8; 95% CI, 2.6-3.0), fibroids (aOR, 2.0; 95% CI, 1.8-2.2), preeclampsia
      (aOR, 3.1; 95% CI, 2.9-3.3), amnionitis (aOR, 2.9; 95% CI, 2.5-3.4), placenta
      previa or abruption (aOR, 7.0; 95% CI, 6.6-7.3), cervical laceration (aOR, 94.0;
      95% CI, 87.3-101.2), uterine rupture (aOR, 11.6; 95% CI, 9.7-13.8), instrumental
      vaginal delivery (aOR, 1.5; 95% CI, 1.4-1.6), and cesarean delivery (aOR, 1.4;
      95% CI, 1.3-1.5). Changes in risk factors, however, accounted for only 5.6% of
      the increase in severe PPH. CONCLUSION: A doubling in incidence of severe PPH
      over 10 years was not explained by contemporaneous changes in studied risk
      factors.

PMID- 23871951
TI  - Confronting safety gaps across labor and delivery teams.
AB  - We assessed the occurrence of 4 safety concerns among labor and delivery teams:
      dangerous shortcuts, missing competencies, disrespect, and performance problems.
      A total of 3282 participants completed surveys, and 92% of physicians (906 of
      985), 93% of midwives (385 of 414), and 98% of nurses (1846 of 1884) observed at
      least 1 concern within the preceding year. A majority of respondents said these
      concerns undermined patient safety, harmed patients, or led them to seriously
      consider transferring or leaving their positions. Only 9% of physicians, 13% of
      midwives, and 13% of nurses shared their full concerns with the person involved.
      Organizational silence is evident within labor-and-delivery teams. Improvement
      will require multiple strategies, used at the personal, social, and structural
      levels. 

PMID- 23871952
TI  - Seasonal variation of suicide in the city of Sao Paulo, Brazil, 1996-2010.
AB  - BACKGROUND: In light of the few reports from intertropical latitudes and their
      conflicting results, we aimed to replicate and update the investigation of
      seasonal patterns of suicide occurrences in the city of Sao Paulo, Brazil.
      METHODS: Data relating to male and female suicides were extracted from the
      Mortality Information Enhancement Program (PRO-AIM), the official health
      statistics of the municipality of Sao Paulo. Seasonality was assessed by studying
      distribution of suicides over time using cosinor analyses. RESULTS: There were
      6,916 registered suicides (76.7% men), with an average of 39.0 +/- 7.0 observed
      suicides per month. For the total sample and for both sexes, cosinor analysis
      estimated a significant seasonal pattern. For the total sample and for males
      suicide peaked in November (late spring) with a trough in May-June (late autumn).
      For females, the estimated peak occurred in January, and the trough in June-July.
      CONCLUSIONS: A seasonal pattern of suicides was found for both males and females,
      peaking in spring/summer and dipping in fall/winter. The scarcity of reports from
      intertropical latitudes warrants promoting more studies in this area.

PMID- 23871953
TI  - Exposure to suicide and identification as survivor. Results from a random-digit
      dial survey.
AB  - BACKGROUND: There is little empirical evidence regarding lifetime exposure to
      suicide or identification of those impacted by suicide deaths. Studies previously
      conducted used only convenience samples. AIMS: To determine the prevalence of
      suicide exposure in the community and those affected by suicide deaths. METHODS:
      A random digit dial sample of 302 adults. RESULTS: 64% of the sample knew someone
      who had attempted or died by suicide, and 40% knew someone who died by suicide.
      No demographic variables differentiated exposed versus unexposed, indicating that
      exposure to suicide cuts across demographics. Almost 20% said they were a
      "survivor" and had been significantly affected by a suicide death. Demographic
      variables did not differentiate groups. The relationship to the decedent was not
      related to self-identified survivor status; what did differentiate those
      individuals impacted by the death from those who did not was their perception of
      their relationship with the decedent. CONCLUSIONS: Kinship proximity and
      relationship category to the deceased appeared to be unrelated to survivor
      status, but perceived psychological closeness to the deceased showed a robust
      association with self-identified survivor status. We need an expanded definition
      of "suicide survivor" to account for the profound impact of suicide in the
      community.

PMID- 23871954
TI  - Responses to a self-presented suicide attempt in social media: a social network
      analysis.
AB  - BACKGROUND: The self-presentation of suicidal acts in social media has become a
      public health concern. AIMS: This article centers on a Chinese microblogger who
      posted a wrist-cutting picture that was widely circulated in Chinese social media
      in 2011. This exploratory study examines written reactions of a group of Chinese
      microbloggers exposed to the post containing a self-harming message and photo. In
      addition, we investigate the pattern of information diffusion via a social
      network. METHODS: We systematically collected and analyzed 5,971 generated
      microblogs and the network of information diffusion. RESULTS: We found that a
      significant portion of written responses (36.6%) could help vulnerable netizens
      by providing peer-support and calls for help. These responses were reposted and
      diffused via an online social network with markedly more clusters of users--and
      at a faster pace-- than a set of randomly generated networks. CONCLUSIONS: We
      conclude that social media can be a double-edged sword: While it may contagiously
      affect others by spreading suicidal thoughts and acts, it may also play a
      positive role by assisting people at risk for suicide, providing rescue or
      support. More research is needed to learn how suicidally vulnerable people
      interact with online suicide information, and how we can effectively intervene.

PMID- 23871955
TI  - Factors associated with attitudes toward suicide: among Japanese pharmacists
      participating in the Board Certified Psychiatric Pharmacy Specialist Seminar.
AB  - BACKGROUND: Pharmacists could play a significant role in providing care for
      suicidal individuals. Previous studies reported that gatekeeper attitudes toward
      suicide could affect caregiving behaviors toward people at risk for suicide.
      Nevertheless, only few studies have examined the attitudes of pharmacists toward
      suicide. AIMS: This study explores the factors associated with the attitudes of
      pharmacists toward suicide. METHODS: A self-administered questionnaire and
      written explanation of the study were mailed to 541 pharmacists who had
      registered for the Board Certified Psychiatry Pharmacy Specialist Seminar in
      Tokyo, Japan. A Japanese version of the Attitudes Toward Suicide questionnaire
      was used to assess participant attitudes toward suicide. Multivariate analysis of
      covariance was used to assess relationships between participant attitudes toward
      suicide as well as demographics, occupational, and personal factors. RESULTS:
      Participants who had previously received suicide-related education were more
      likely to have positive attitudes toward suicide prevention. Conversely, those
      with a lifetime history of suicidal thoughts had more permissive attitudes toward
      one's right to commit suicide. CONCLUSIONS: Our findings suggest that pharmacist
      suicide prevention training programs should aim to alter permissiveness attitudes
      of trainees toward suicide.

PMID- 23871956
TI  - Fractional parentage analysis and a scale-free reproductive network of brown
      trout.
AB  - In this study, we developed a method of fractional parentage analysis using
      microsatellite markers. We propose a method for calculating parentage
      probability, which considers missing data and genotyping errors due to null
      alleles and other causes, by regarding observed alleles as realizations of random
      variables which take values in the set of alleles at the locus and developing a
      method for simultaneously estimating the true and null allele frequencies of all
      alleles at each locus. We then applied our proposed method to a large sample
      collected from a wild population of brown trout (Salmo trutta). On analyzing the
      data using our method, we found that the reproductive success of brown trout
      obeyed a power law, indicating that when the parent-offspring relationship is
      regarded as a link, the reproductive system of brown trout is a scale-free
      network. Characteristics of the reproductive network of brown trout include
      individuals with large bodies as hubs in the network and different power
      exponents of degree distributions between males and females. 

PMID- 23871957
TI  - A critical study of network models for neural networks and their dynamics.
AB  - We use three network models, Erdos-Renyi, Watts-Strogatz and structured nodes, to
      generate networks sharing several topological features with the neural network of
      C. elegans (our target network). A new topological measurement, incoming and
      outgoing edges heat maps, is introduced and used to compare the considered
      networks. We run these networks as random recurrent neural networks and study
      their dynamics. We find out that none of the considered network models generates
      networks similar to the target one both in their topological features and
      dynamics. Moreover, we find that the dynamics of the target network are very
      robust to the rewiring of its edges. 

PMID- 23871958
TI  - Suggested phylogeny of tRNAs based on the construction of ancestral sequences.
AB  - The origin and evolution of life on the planet is one of the most intriguing
      challenges in life sciences and, for some researchers, it is centered in the
      origin of the genetic code. Many hypotheses about the origin and evolution of
      tRNA have been proposed and in this work a new suggestion is proposed based on
      the reconstruction of tRNA ancestor sequences. Ancestral sequences of 22 types of
      tRNA molecules were built by maximum likelihood from 9758 sequences currently
      reported from different organisms. Phylogenetic analysis showed that the main
      force for evolutionary diversification of tRNA molecules was a change in the
      second base of the anticodon. The data revealed that diversification is not
      correlated with the characteristic of the specified amino acid, indicating that
      the correlation between tRNA and amino acid was given indirectly, and possibly
      should have been mediated by proto-aminoacyl-tRNA synthetases. 

PMID- 23871959
TI  - A comparative study between nanoparticle-targeted therapeutics and bioconjugates
      as obesity medication.
AB  - Antiangiogenesis has been the focus of a new strategy for the treatment of
      obesity. However, little is known regarding the issue of whether targeting
      angiogenesis by nanoparticle-targeted therapeutic is advantageous or not in
      debugging the co-morbidity associated with diet-induced obesity (DIO) and the
      metabolic syndrome. We report herein on the positive effect of prohibitin (an
      adipose vascular marker)-targeted nanoparticle (PTNP) encapsulated in a
      proapoptotic peptide [(D)(KLAKLAK)2, KLA] on DIO and dysfunctional adipose
      tissue, a major mediator of the metabolic syndrome, as evidenced by ectopic fat
      deposition. The systemic injection of DIO mice with a low dose of KLA-PTNP,
      rather than a bioconjugate composed of the same targeting peptide and KLA
      (Adipotide) resulted in a reduction in body weight, as evidenced by a significant
      decrease in serum leptin levels, in parallel with an antiobesity effect on
      dysfunctional adipose cells, including adipocytes and macrophages. In addition,
      the KLA-PTNP treatment resulted in a reduction in ectopic fat deposits in liver
      and muscle with the lipolytic action of elevated serum adiponectin, with no
      detectable hepatoxicity. Notably, drug delivery via PTNP that had accumulated in
      obese fat via the enhanced permeability and retention effect was enhanced by
      multivalent active targeting and cytoplasmic delivery into adipose endothelial
      cells via escaping from endosomes/lysosomes. Thus, vascular-targeted nanotherapy
      has the potential to contribute to the control of adipose function and ectopic
      fat deposition associated with obesity and the metabolic syndrome.

PMID- 23871961
TI  - Dual-mode enhancement of metallothionein protein with cell transduction and
      retention peptide fusion.
AB  - Protein transduction domains (PTDs), also known as cell-penetrating peptides
      (CPPs), have been developed as effective systems for delivering bio-active cargos
      such as proteins, genes and particles. Further improvements on cell-specific
      targeting, intracellular organelle targeting and intracellular retention are
      still necessary to enhance the therapeutic effect of PTD fusion proteins. In
      order to enhance the cell transduction and retention of anti-oxidative
      metallothionein protein (MT), MT was recombinantly fused with transcriptional
      activator (Tat) with or without a short peptide (sMTS) derived from mitochondria
      malate dehydrogenase (mMDH). Cellular uptake and retention time of fusion protein
      were significantly increased in the H9c2 cell by sMTS. The Tat-sMTS-MT (TMM)
      fusion protein protected H9c2 cells more effectively against hypoxia,
      hyperglycemia and combination compared with Tat-MT (TM) by reducing intracellular
      ROS level. It maintained the normal blood glucose level over an extended period
      of time in a streptozotocin-induced diabetic mouse model. PTD-sMTS-MT fusion
      protein has a potential to be used as a therapeutic protein for the treatment or
      prevention of diabetes and diabetic complications. 

PMID- 23871960
TI  - Drug-loaded sickle cells programmed ex vivo for delayed hemolysis target hypoxic
      tumor microvessels and augment tumor drug delivery.
AB  - Selective drug delivery to hypoxic tumor niches remains a significant therapeutic
      challenge that calls for new conceptual approaches. Sickle red blood cells
      (SSRBCs) have shown an ability to target such hypoxic niches and induce
      tumoricidal effects when used together with exogenous pro-oxidants. Here we
      determine whether the delivery of a model therapeutic encapsulated in murine
      SSRBCs can be enhanced by ex vivo photosensitization under conditions that delay
      autohemolysis to a time that coincides with maximal localization of SSRBCs in a
      hypoxic tumor. Hyperspectral imaging of 4T1 carcinomas shows oxygen saturation
      levels <10% in a large fraction (commonly 50% or more) of the tumor. Using video
      microscopy of dorsal skin window chambers implanted with 4T1 tumors, we
      demonstrate that allogeneic SSRBCs, but not normal RBCs (nRBCs), selectively
      accumulate in hypoxic 4T1 tumors between 12 and 24h after systemic
      administration. We further show that ex vivo photo-oxidation can program SSRBCs
      to postpone hemolysis/release of a model therapeutic to a point that coincides
      with their maximum sequestration in hypoxic tumor microvessels. Under these
      conditions, drug-loaded photosensitized SSRBCs show a 3-4 fold greater drug
      delivery to tumors compared to non-photosensitized SSRBCs, drug-loaded
      photosensitized nRBCs, and free drug. These results demonstrate that photo
      oxidized SSRBCs, but not photo-oxidized nRBCs, sequester and hemolyze in hypoxic
      tumors and release substantially more drug than photo-oxidized nRBCs and non
      photo-oxidized SSRBCs. Photo-oxidation of drug-loaded SSRBCs thus appears to
      exploit the unique tumor targeting and carrier properties of SSRBCs to optimize
      drug delivery to hypoxic tumors. Such programmed and drug-loaded SSRBCs therefore
      represent a novel and useful tool for augmenting drug delivery to hypoxic solid
      tumors.

PMID- 23871962
TI  - CD133-targeted paclitaxel delivery inhibits local tumor recurrence in a mouse
      model of breast cancer.
AB  - Expression of the membrane protein CD133 marks a subset of cancer cells with drug
      resistant phenotype and enhanced tumor initiating ability in xenotransplantation
      assays. Because drug resistance and tumor relapse are significant problems,
      approaches to eliminate these cells are urgently needed. As a step towards
      achieving this goal, we developed polymeric nanoparticles targeting CD133 by
      conjugating an anti-CD133 monoclonal antibody to nanoparticles formulated using
      poly(D,L lactide-co-glycolide) polymer. Nanoparticles were loaded with
      paclitaxel, a microtubule-stabilizing anticancer agent, as well as with 6
      coumarin, a fluorescent probe. CD133-targeted nanoparticles (CD133NPs) were
      efficiently internalized by Caco-2 cells, which abundantly express CD133 (>9-fold
      higher uptake than non-targeted control nanoparticles). The effectiveness of
      CD133NPs in reducing tumor initiating cell (TIC) fraction was investigated using
      mammosphere formation and soft-agar colony formation assays. Free paclitaxel
      treatment was not effective in decreasing the TIC population relative to
      untreated control, whereas CD133NPs effectively decreased the number of
      mammospheres and colonies formed. In vivo studies in the MDA-MB-231 xenograft
      model showed that free paclitaxel was initially effective in inhibiting tumor
      growth but the tumors rebounded rapidly once the treatment was stopped. Tumor
      regrowth was significantly lower when paclitaxel was delivered through CD133NPs
      (tumor volume was 518.6+/-228 vs. 1370.9+/-295mm(3) for free paclitaxel at
      63days; P<0.05). Our studies thus show that encapsulation of paclitaxel in
      CD133NPs results in a significant decrease in the TIC population and improved
      therapeutic efficacy compared to that with free paclitaxel treatment. These
      results indicate the potential of targeting anticancer therapeutics to CD133+
      cells for reducing tumor recurrence. 

PMID- 23871963
TI  - A theoretical framework for quantifying blood volume flow rate from dynamic
      angiographic data and application to vessel-encoded arterial spin labeling MRI.
AB  - Angiographic methods can provide valuable information on vessel morphology and
      hemodynamics, but are often qualitative in nature, somewhat limiting their
      ability for comparison across arteries and subjects. In this work we present a
      method for quantifying absolute blood volume flow rates within large vessels
      using dynamic angiographic data. First, a kinetic model incorporating relative
      blood volume, bolus dispersion and signal attenuation is fitted to the data. A
      self-calibration method is also described for both 2D and 3D data sets to convert
      the relative blood volume parameter into absolute units. The parameter values are
      then used to simulate the signal arising from a very short bolus, in the absence
      of signal attenuation, which can be readily encompassed within a vessel mask of
      interest. The volume flow rate can then be determined by calculating the
      resultant blood volume within the vessel mask divided by the simulated bolus
      duration. This method is applied to non-contrast magnetic resonance imaging data
      from a flow phantom and also to the cerebral arteries of healthy volunteers
      acquired using a 2D vessel-encoded pseudocontinuous arterial spin labeling pulse
      sequence. This allows the quantitative flow contribution in downstream vessels to
      be determined from each major brain-feeding artery. Excellent agreement was found
      between the actual and estimated flow rates in the phantom, particularly below
      4.5 ml/s, typical of the cerebral vasculature. Flow rates measured in healthy
      volunteers were generally consistent with values found in the literature. This
      method is likely to be of use in patients with a variety of cerebrovascular
      diseases, such as the assessment of collateral flow in patients with steno
      occlusive disease or the evaluation of arteriovenous malformations.

PMID- 23871964
TI  - A new fast algorithm for solving the minimum spanning tree problem based on DNA
      molecules computation.
AB  - The minimum spanning tree (MST) problem is to find minimum edge connected subsets
      containing all the vertex of a given undirected graph. It is a vitally important
      NP-complete problem in graph theory and applied mathematics, having numerous real
      life applications. Moreover in previous studies, DNA molecular operations usually
      were used to solve NP-complete head-to-tail path search problems, rarely for NP
      hard problems with multi-lateral path solutions result, such as the minimum
      spanning tree problem. In this paper, we present a new fast DNA algorithm for
      solving the MST problem using DNA molecular operations. For an undirected graph
      with n vertex and m edges, we reasonably design flexible length DNA strands
      representing the vertex and edges, take appropriate steps and get the solutions
      of the MST problem in proper length range and O(3m+n) time complexity. We extend
      the application of DNA molecular operations and simultaneity simplify the
      complexity of the computation. Results of computer simulative experiments show
      that the proposed method updates some of the best known values with very short
      time and that the proposed method provides a better performance with solution
      accuracy over existing algorithms. 

PMID- 23871965
TI  - The complex fluctuations of probabilistic Boolean networks.
AB  - Probabilistic Boolean networks (PBNs) are extensions of Boolean networks (BNs),
      and both have been widely used to model biological systems. In this paper, we
      study the long-range correlations of PBNs based on their corresponding Markov
      chains. PBN states are quantified by the deviation of their steady-state
      distributions. The results demonstrate that, compared with BNs, PBNs can exhibit
      these dynamics over a wider and higher noise range. In addition, the constituent
      BNs significantly impact the generation of 1/f dynamics of PBNs, and PBNs with
      homogeneous steady-state distributions tend to sustain the 1/f dynamics over a
      wider noise range. 

PMID- 23871967
TI  - Measurement of steroids in rats after exposure to an endocrine disruptor: mass
      spectrometry and radioimmunoassay demonstrate similar results.
AB  - INTRODUCTION: Commercially available radioimmunoassays (RIAs) are frequently used
      to evaluate the effects of endocrine disrupting chemicals (EDCs) on
      steroidogenesis in rats. Currently there are limited data comparing steroid
      concentrations in rats as measured by RIAs to those obtained using liquid
      chromatography coupled with tandem mass spectrometry (LC-MS/MS). This study
      evaluates the concordance of serum and urine steroid concentrations as quantified
      by select RIA kits and LC-MS/MS following exposure to an EDC, atrazine (ATR).
      METHODS: Adult male rats were orally dosed with ATR (200 mg/kg/day) or
      methylcellulose (1%, vehicle control) for 5 days. Serum was collected and
      separated into aliquots for analysis. Serum was assayed by RIA for
      androstenedione (ANDRO), corticosterone (CORT), estradiol (E2), estrone (E1),
      progesterone (P4), and testosterone (T). Serum was extracted prior to LC-MS/MS
      analysis with positive electrospray ionization in multiple-reaction monitoring
      mode for ANDRO, CORT, P4, and T. E1 and E2 concentrations were quantified
      similarly by LC-MS/MS, following derivatization with dansyl chloride. To compare
      CORT values from urine, pregnant adult rats were orally dosed with either ATR
      (100 mg/kg/day) or methylcellulose for 5 days (i.e., gestational days 14-18).
      Urine samples were collected daily and assayed for CORT by RIA and LC-MS/MS as
      described above. RESULTS: Data analyses demonstrated significant agreement
      between the two detection methods as assessed by Pearson product-moment
      correlation coefficient, Bland-Altman analysis, and the interclass correlation
      coefficient. No statistically significant differences were observed between RIA
      and LC-MS/MS means for any of the steroids assayed. DISCUSSION: These findings
      indicate a significant correlation between the measurement of steroids within rat
      serum and urine using RIA kits and LC-MS/MS. Differences in the absolute
      measurements existed, but these were not statistically significant. These
      findings indicate that steroids may be reliably measured in rat biological media
      using RIAs or LC-MS/MS.

PMID- 23871969
TI  - Use of uranium isotopes as a temporal and spatial tracer of nuclear contamination
      in the environment.
AB  - The Fernald Feed Materials Production Center (FFMPC) was established in 1951 to
      process natural uranium (U) ore, enriched uranium (EU) and depleted uranium (DU).
      This study tests the utility of U isotopic ratios in sediment cores and lichens
      as indicators of the aerial extent, degree and timing of anthropogenic U
      contamination, using the FFMPC as a test case. An 80-cm-long sediment core was
      extracted from an impoundment located approximately 6.7 km southwest of the
      FFMPC. Elemental concentrations of thorium (2.7-6.2 MUg g(-1)) and U (0.33-1.33
      MUg g(-1)) as well as major and minor U isotopes were analyzed in the core. The
      lack of measurable (137)Cs in the deepest sample as well as a natural
      (235)U/(238)U signature and no measurable (236)U, are consistent with pre-FFMPC
      activity. Anomalously elevated U with respect to Th concentrations occur in seven
      consecutive samples immediately above the base of the core (62-76 cm depth).
      Samples with elevated U concentrations also show variable (235)U/(238)U (0.00645
      0.00748), and all contain measurable (236)U ((236)U/(238)U = 2.1 * 10(-6)-3.6 *
      10(-5)). Correspondence between the known releases of U dust from the FFMPC
      through time and variations in sediment core U concentrations, (235)U/(238)U and
      (236)U/(238)U ratios provide evidence for distinct releases of both DU and EU.
      Furthermore, these relationships demonstrate that the sediment core serves as a
      robust archive of past environmental U contamination events. Samples in the upper
      40 cm display natural (235)U/(238)U, but measurable (236)U/(238)U ((236)U/(238)U
      = 5.68 * 10(-6)-1.43 * 10(-5)), further indicating the continued presence of
      anthropogenic U in present-day sediment. Three local lichen samples were also
      analyzed, and all display either EU or DU signatures coupled with elevated
      (236)U/(238)U, recording airborne U contamination from the FFMPC. 

PMID- 23871968
TI  - Estimating the distribution of radionuclides in agricultural soils - dependence
      on soil parameters.
AB  - In this study it is shown how radionuclide distributions in agricultural soils
      and their dependence on soil parameters can be quantitatively estimated. The most
      important sorption and speciation processes have been implemented into a
      numerical model using the geochemical code PHREEQC that is able to include
      specific soil and soil solution compositions. Using this model, distribution
      coefficients (Kd values) for the elements Cs, Ni, U and Se have been calculated
      for two different soil types. Furthermore, the dependencies of these Kd values on
      various soil parameters (e.g. pH value or organic matter content) have been
      evaluated. It is shown that for each element, an individual set of soil
      parameters is relevant for its solid-liquid distribution. The model may be used
      for the calculation of input parameters used by reference biosphere models (e.g.
      used for the risk assessment of nuclear waste repositories). 

PMID- 23871966
TI  - Mechanisms of HCV-induced liver cancer: what did we learn from in vitro and
      animal studies?
AB  - Hepatitis C virus (HCV) is a cause of liver diseases that range from
      steatohepatitis, to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The
      challenge of understanding the pathogenesis of HCV-associated liver cancer is
      difficult as most standard animal models used in biomedical research are not
      permissive to HCV infection. Herein, we provide an overview of a number of
      creative in vivo, mostly in the mouse, and in vitro models that have been
      developed to advance our understanding of the molecular and cellular effects of
      HCV on the liver, specifically with their relevance to HCC. 

PMID- 23871970
TI  - Application of rapid cloud point extraction method for trace cobalt analysis
      coupled with spectrophotometric determination.
AB  - In this work, the analytical performance of conventional spectrophotometer was
      improved through the coupling of effective preconcentration method with
      spectrophotometric determination. Rapidly synergistic cloud point extraction (RS
      CPE) was used to pre-concentrate ultra trace cobalt and firstly coupled with
      spectrophotometric determination. The developed coupling was simple, rapid and
      efficient. The factors influencing RS-CPE and spectrophotometer were optimized.
      Under the optimal conditions, the limit of detection (LOD) was 0.6MUgL(-1), with
      sensitivity enhancement factor of 23. The relative standard deviation (RSD) for
      seven replicate measurements of 50MUgL(-1) of cobalt was 4.3%. The recoveries for
      the spiked samples were in the acceptable range of 93.8-105%. 

PMID- 23871971
TI  - Potential toxicity of sarafloxacin to catalase: spectroscopic, ITC and molecular
      docking descriptions.
AB  - The interaction between sarafloxacin and catalase (CAT) was studied by
      fluorescence spectroscopy, UV-visible absorption spectroscopy, circular dichroism
      (CD) spectroscopy, isothermal titration microcalorimetry (ITC) and molecular
      docking method. After deducting the inner filter effect, the fluorescence of CAT
      was quenched regularly by different concentrations of sarafloxacin. The quenching
      mechanism was studied by lifetime measurement, and it was proved to be mostly due
      to static quenching. The formation of sarafloxacin-CAT complex alters the micro
      environment of amide moieties and tryptophan (Trp) residues, reduces the alpha
      helix content of the enzyme, changes the peripheral substituents on the porphyrin
      ring of heme and leads to the inhibition of the enzyme activity. Molecular
      docking study reveals that sarafloxacin is located between two alpha-helix of CAT
      near to Trp 182 and Trp 185 residues, which supports the experimental results and
      helps to have a more clear understanding about the interaction mechanism. The
      change in the relative position of His 74 to heme induced by the variation of
      secondary structure is considered to be the major reason for the reduction of CAT
      activity. Moreover, sarafloxacin binds into a hydrophobic area of CAT mainly
      through hydrophobic interactions, which is consistent with the ITC analysis. 

PMID- 23871972
TI  - Theoretical investigations of the structures and electronic spectra of 8
      hydroxylquinoline derivatives.
AB  - The spectroscopic properties of 8-hydroxyquinoline derivatives are theoretically
      investigated by means of density functional theory (DFT) and time-dependent
      density functional theory (TD-DFT) methods. The target molecules are divided into
      two groups: group (I): (E)-2-(2-(3,5-dimethyl-1-phenyl-1H-pyrazol-4
      yl)vinyl)quinolin-8-ol (A), together with corresponding potential reaction
      products of A with acetic acid, i.e., (E)-2-(2-(3,5-dimethyl-1-phenyl-1H-pyrazol
      4-yl)vinyl)quinolin-8-yl acetate (AR1), and (E)-2-(2-(3,5-dimethyl-1-phenyl-1H
      pyrazol-4-yl)vinyl)-8-hydroxyquinolinium (AR2); group (II): (E)-2-(2-(1-(4
      chlorophenyl)-3,5-dimethyl-1H-pyrazol-4-yl)vinyl)quinolin-8-ol (B), as well as
      potential reaction products of B with acetic acid, i.e., (E)-2-(2-(1-(4
      chlorophenyl)-3,5-dimethyl-1H-pyrazol-4-yl)vinyl)quinolin-8-yl acetate (BR1), and
      (E)-2-(2-(1-(4-chlorophenyl)-3,5-dimethyl-1H-pyrazol-4-yl)vinyl)-8
      hydroxyquinolinium (BR2). The geometries are optimized by B3LYP and M06 methods.
      The results indicate that product molecules tend to be effectively planar
      compared with reactants. Subsequently, UV absorption spectra are simulated
      through TD-DFT method with PCM model to further confirm the reasonable products
      of two reactions. AR2 and BR2 are identified as the target molecules through the
      experimental spectra for the real products. It is worth noting that the maximum
      absorption wavelengths of compounds AR2 and BR2 present prominent red shift
      compared the initial reactants A and B, respectively, which should be ascribed to
      the enhancive planarity of products that mentioned above and the decreased HOMO
      LUMO energy gap. Geometric structures and optical properties for corresponding
      compounds are discussed in detail. 

PMID- 23871973
TI  - Design and synthesis of novel complexes containing N-phenyl-1H-pyrazole moiety:
      Ni complex as potential antifungal and antiproliferative compound.
AB  - Cu(II) (1), Ni(II) (2), Cr(III) (3) and Fe(III) (4) complexes with 3-acetyl-4
      benzoyl-1-phenyl-1H-pyrazole (L1) were prepared and structurally characterized.
      Usual coordination of L1 was achieved through nitrogen of pyrazole moiety and
      carbonyl acetyl group. Electronic spectra of the complexes indicate that the
      geometry of the metal center was six coordinate octahedral. In vitro
      antimicrobial activity of the ligand and complex compounds was screened in terms
      of antibacterial effect on Staphylococcus aureus (Gram-positive), Escherichia
      coli (Gram-negative) and antifungal effect on the fungi Aspergillus flavus and
      candida albicans using the modified Kirby-Bauer disc diffusion and minimum
      inhibitory concentrations (MIC) methods. Ni(II) complex (2) exhibited remarkable
      antifungal inhibition against Candida albicans equal to the standard antifungal
      agent. To continue our study some structural modifications are formed by adding 4
      fluoro-benzoyl moiety to L1 in different forms to produce different ligands, 3
      acetyl-4-(4-flourobenzoyl)-1-phenyl-1H-pyrazole (L2) and 3-[(3-acetyl-1-phenyl-1H
      4-pyrazolyl)carbonyl]-1-phenyl-4-(4-flourobenzoyl)-1H-pyrazole (L3), Ni complexes
      (5 and 6) are prepared and comparable in vitro antimicrobial study is evaluated.
      In vitro cytotoxicity of the Ni(II) complex (2) is studied using MTT assay. The
      analysis of the cell test showed that (2) displayed quite small cytotoxic
      response at the higher concentration level which indeed would further enable us
      for more opportunities in therapeutic and biomedical challenges. Both of the
      capability as a potent in vitro antifungal agent and the cell test analysis show
      Ni(II) complex (2) as a promising material in the translation of observed in
      vitro biological phenomenon into clinical therapies settings. 

PMID- 23871974
TI  - Synthesis, structures and properties of the catalytic bromination reaction of a
      series of novel scorperate oxidovanadium complexes with the potential detection
      of hydrogen peroxide in water.
AB  - A series of scorpionate oxovanadium (IV) complexes:
      [VO(Tp(4I))(pz)(SCN)].1/2CH2Cl2 (1), [VO(Tp)(pzTp)].2H2O (2), [VO(Bp)(Tp(4I))]
      (3) and [VO(C5H7O2)(Tp(4I))].CH3OH (4) (Bp: [H2B(pz)(2-)], Tp: [HB(pz)(3-)],
      Tp(4I): [HB(4I-pz)(3-)], pzTp: [B(pz)(4-)]) have been synthesized and
      characterized by elemental analysis, IR spectra, UV-Vis spectroscopy, powder X
      ray diffraction, single-crystal X-ray diffraction and thermal gravimetric
      analysis (TG). Structural analysis shows that the coordination environment of
      vanadium atom is N5O, to form a distorted octahedron geometry. In addition, the
      catalytic activities of the bromination reactions for complexes 1 and 2 in
      phosphate buffer with phenol red as a trap were evaluated primary by UV/Vis
      spectroscopy, and a practical application of H2O2 detection was firstly observed
      in the catalytic reaction system. 

PMID- 23871975
TI  - Theoretical investigation of optical and paramagnetic resonance spectra of
      [NiF6](4-) clusters with orthorhombic symmetry.
AB  - The ground state absorption spectra of [NiF6](4-) clusters with orthorhombic
      symmetry (Ni(2+) in NiF2 crystal and Ni(2+)-doped ZnF2 crystal, D2h point group)
      are theoretically calculated and assigned by diagonalization of 45*45 complete
      energy matrix for 3d(8) configuration and the spin-Hamiltonian (SH) parameters
      (zero-field splitting D and E, and g factors gx, gy, gz) are studied by use of
      high-order perturbation method, in the frame of semi-empirical molecular orbital
      (MO) scheme based on strong crystal field framework. In those energy matrix, all
      the configuration interactions though the cubic crystal field (CF), the
      orthorhombic crystal field, the Coulomb interaction are taken into account. The
      calculated results are in good agreement with the experimental data. The local
      structure (bond length and bond angle) of [NiF6](4-) clusters are determined, and
      the results shows that the structure data given by Stout are more plausible than
      those given by Baur. 

PMID- 23871976
TI  - Contrasting emission behaviour of phenanthroimidazole with ZnO nanoparticles.
AB  - A new fluorophore 2-(4-fluorophenyl)-1-phenyl-1H-phenanthro [9,10-d]imidazole has
      been synthesized and characterized by spectroscopic techniques. Nanoparticulate
      ZnO enhances the fluorescence of the synthesised fluorophore. The absorption,
      fluorescence, lifetime, cyclic voltammetry and infrared studies reveal that
      fluorophore is attached to the surface of ZnO semiconductor. Photo-induced
      electron transfer (PET) explains the enhancement of fluorescence by
      nanoparticulate ZnO and the apparent binding constant has been obtained.
      Adsorption of the fluorophore on ZnO nanoparticle lowers the HOMO and LUMO energy
      levels of the fluorophore. The strong adsorption of the phenanthrimidazole
      derivative on the surface of ZnO nanocrystals is likely due to the chemical
      affinity of the nitrogen atom of the organic molecule to the zinc ion on the
      surface of nanocrystal. 

PMID- 23871977
TI  - Vibrational and theoretical study of selected diacetylenes.
AB  - Six commonly used disubstituted diacetylenes with short side-chains (RCCCCR,
      where R=CH2OH, CH2OPh, C(CH3)2OH, C(CH3)3, Si(CH3)3, and Ph) were analyzed using
      vibrational spectroscopy and quantum-chemical calculations to shed new light on
      structural and spectroscopic properties of these compounds. Prior to that the
      conformational analysis of diacetylenes was performed to search the Potential
      Energy Surface for low-energy minima. Theoretical investigations were followed by
      the potential energy distribution (PED) analysis to gain deeper insight into FT
      Raman and FT-IR spectra that, in some cases, were recorded for the first time for
      the studied compounds. The analysis was focused mainly on spectral features of
      the diacetylene system sensitive to the substitution. Shifts of the
      characteristic bands and changes in bond lengths were observed when changing the
      substituent. Furthermore, Fermi resonance was observed in the vibrational spectra
      of some diacetylenes. FT-IR spectra were measured by using two methods, i.e.
      transmission (with KBr substrate) and Attenuated Total Reflection (ATR), showing
      the latter adequate and fast tool for IR measurements of diacetylenes.
      Additionally, Surface Enhanced Raman Spectroscopy (SERS) was applied for phenyl
      derivative for the first time to study its interaction with metallic
      nanoparticles that seems to be perpendicular. 

PMID- 23871978
TI  - Vibrational and reorientational motions of H2O ligands, phase transition and
      thermal properties of [Sr(H2O)6]Cl2.
AB  - One phase transition (PT) at TC(h)=252.9K (on heating) and at TC(c)=226.5K (on
      cooling) was detected by DSC for [Sr(H2O)6]Cl2 in 123-295K range. Thermal
      hysteresis of this PT equals to 26.4K. Entropy change (DeltaS) value at this
      first-order type phase transition equals to ca. 1.5Jmol(-1)K(-1). The temperature
      dependences of the full width at half maximum (FWHM) values of the infrared bands
      associated with rhot(H2O)E and deltaas(HOH)E modes (at ca. 417 and 1628cm(-1),
      respectively) suggest that the observed phase transition is associated with a
      sudden change of a speed of the H2O reorientational motions. The H2O ligands in
      the high temperature phase reorientate quickly (correlation times 10(-11)-10(
      13)s) with the activation energy of ca. 2kJmol(-1). Below TC(c) probably a part
      of the H2O ligands stop their reorientation, while the remainders continue their
      fast reorientation but with the activation energy of ca. 8kJmol(-1). Far and
      middle infrared spectra indicated characteristic changes at the vicinity of PT
      with decreasing of temperature, which suggested lowering of the crystal structure
      symmetry. Splitting of the band (at 3601cm(-1)) connected with vas(OH) mode near
      the TC(c) suggests lowering of the crystal lattice symmetry. All these facts
      suggest that the discovered PT is connected both with a change of the
      reorientational dynamics of the H2O ligands and with the change of the crystal
      structure. 

PMID- 23871979
TI  - Controlled growth, intense upconversion emissions and concentration induced
      luminescence switching of bifunctional Tm(3+) doped hexagonal NaYb0.55Gd0.45F4
      nanorods.
AB  - Bifunctional hexagonal Tm(3+) doped NaYb0.55Gd0.45F4 nanorods with tunable size
      are prepared via in situ cation-exchange reaction using hydrothermal method. The
      measured field dependence of magnetization of the NaYb0.55Gd0.45F4 nanorods shows
      typical paramagnetic characteristics that can be ascribed to the non-interacting
      localized nature of the magnetic moment of rare-earth ions. When excited by a
      980nm laser, these nanorods exhibit intense multi-color up-conversion (UC)
      emissions in infrared, red, blue and especially ultraviolet. In addition,
      luminescent switching between different UC emission wavelengths of 480nm and
      450nm is observed by adjusting Tm(3+) doping concentration. Based on power
      dependent spectral analyses, it is found that with the increase of Tm(3+) doping
      concentration, due to the suppressed saturation effect, the dominative UC process
      redistribute the populations at (1)G4 and (1)D2(Tm(3+)) states of Tm(3+) ion
      resulting in the above luminescent switching. Our results indicate that
      bifunctional hexagonal NaYb1-xGdxF4 nanocrystals have potential applications in
      miniaturized solid-state light sources, optical processing sensors and
      fluorescent biolabels. 

PMID- 23871980
TI  - Investigation of interaction of nuclear fast red with human serum albumin by
      experimental and computational approaches.
AB  - For the first time, interaction of nuclear fast red (NFR) with human serum
      albumin (HSA) was studied by experimental and computational approaches. Firstly,
      experimental measurements including fluorescence spectroscopy (F), UVvis
      spectrophotometry (UVvis), cyclic voltammetry (CV), differential pulse
      voltammetry (DPV) and linear sweep voltammetry (LSV) were separately used to
      investigate the interaction of NFR with HSA and interesting thermodynamics
      information was obtained from these studies. Secondly, new information including
      electrochemical behavior of NFR-HSA complex species, relative concentrations of
      the various reacting species and effects of NFR on the sub-structure of HSA was
      obtained by applying multivariate curve resolution-alternating least squares (MCR
      ALS). In this case, a row- and column-wise augmented matrix was built with DPV,
      LSV, F and UVvis sub-matrices and resolved by MCR-ALS. Surprisingly, by this
      method two NFR-HSA complex species with different stoichiometries and different
      electrochemical behaviors were found. Furthermore, by the use of the recorded
      voltammetric and spectroscopic data the binding constants of complex species were
      computed by EQUISPEC (a hard-modeling algorithm). Finally, the binding of NFR to
      HSA was modeled by molecular modeling and molecular dynamics (MD) simulations
      methods. Excellent agreement was found between experimental and computational
      results. Both experimental and computational results suggested that the NFR binds
      mainly to the sub-domain IIA of HSA. 

PMID- 23871981
TI  - Cage occupancy and structural changes during hydrate formation from initial
      stages to resulting hydrate phase.
AB  - Hydrate formation processes and kinetics are still not sufficiently understood on
      a molecular level based on experimental data. In particular, the cavity formation
      and occupancy during the initial formation and growth processes of mixed gas
      hydrates are rarely investigated. In this study, we present the results of our
      time-depending Raman spectroscopic measurements during the formation of hydrates
      from ice and gases or gas mixtures such as CH4, CH4-CO2, CH4-H2S, CH4-C3H8, CH4
      iso-C4H10, and CH4-neo-C5H12 at constant pressure and temperature conditions and
      constant composition of the feed gas phase. All investigated systems in this
      study show the incorporation of CH4 into the 5(12) cavities as first step in the
      initial stages of hydrate formation. Furthermore, the results imply that the
      initial hydrate phases differ from the resulting hydrate phase having reached a
      steady state regarding the occupancy and ratio of the small and large cavities of
      the hydrate. 

PMID- 23871982
TI  - Time resolved high frequency spectrum of Br2 molecules using pulsed photoacoustic
      technique.
AB  - The paper reports the time resolved spectral distribution of higher order
      acoustic modes generated in Br2 molecules using pulsed Photoacoustic (PA)
      technique. New time resolved vibrational spectrum of Br2 molecules are recorded
      using a single 532nm, pulses of 7ns duration at 10Hz repetition rate obtained
      from Q-switched Nd:YAG laser. Frank-Condon principle based assignments confirms
      the presence of 12 numbers of (nu"-nu') vibrational transitions covered by a
      single 532+2nm pulse profile. Inclusions of higher order zeroth modes in Bassel's
      function expansion series shows the probability of overlapping of different types
      of acoustic modes in the designed PA cells. These modes appear in the form of
      clusters which occupies higher frequency range. The study of decay behavior of PA
      signal with respect to time confirms the photolysis of Br2 at 532nm wavelength.
      In addition, the shifting and clustering effect of cavity eigen modes in Br2
      molecules have been studied between 1 and 10ms time scale. The estimated Q-factor
      of PA cell (l=16cm, R=1.4cm) is 145+/-4 at 27kHz frequency. 

PMID- 23871983
TI  - A new selective colorimetric and fluorescent chemodosimeter for HSO4(-) based on
      hydrolysis of Schiff base.
AB  - Two new receptors 1 and 2 were prepared, and their chromogenic and fluorogenic
      behaviors toward various anions were investigated. Receptors 1 and 2 show
      exclusive response toward HSO4(-) ion and also distinguish HSO4(-) from other
      anions by different color changes in aqueous solution (CH3CN/H2O=4/1, v/v).
      Between them receptor 1 selectively exhibits a pronounced HSO4(-)-induced
      fluorescence enhancement. The detection limit for the HSO4(-) ion was determined
      as (0.24+/-0.03MUM). Thus, the receptor 1 can be used as a colorimetric and
      fluorescent sensor for the determination of HSO4(-) ion. The sensing mechanism
      has been suggested to proceed via a hydrolysis process. The hydrolysis product
      has been isolated and further identified by (1)H NMR spectroscopy, ESI-MS
      analysis and X-ray diffraction. 

PMID- 23871984
TI  - Synthesis and spectroscopic characterization of 3,4-difluoroacetophenone
      thiosemicarbazone and its palladium(II) complex: evaluation of antimicrobial and
      antitumour activity.
AB  - A new cis-palladium(II)diaqua(3,4-difluoroacetophenonethiosemicarbazone complex
      (Pd(II) complex) is synthesized using 3,4
      difluoroacetophenonethiosemicarbazone(L). The L and its Pd(II) complex are
      characterized and confirmed by elemental analyses, electrochemical analyses, FT
      IR, FT-Raman, UV-Vis, HRMS and LC-MS techniques. Ligand L is further
      characterized by (1)H, (13)C and (19)F NMR spectroscopy. The crystal structure of
      L is unambiguously characterized by single X-ray crystallography. The ligand (L)
      belongs to monoclinic system with P2(1)/C space group and the unit cell
      parameters are a(A)=9.1144(7), b(A)=13.7928(7), c(A)=8.4174(5), alpha( degrees
      )=90, beta( degrees )=100.715, gamma( degrees )=90 and volume
      V(A(3))=1039.73(11). The Raman bands observed for the L and its Pd(II) complex
      are in good agreement with the FT-IR spectral data. The Pd(II) complex is found
      to be highly efficient in inhibiting the growth of human pathogens like
      Salmonella typhimurium and Klebsiella pneumonia with MIC value 10.0MUg/mL whose
      inhibition zones are almost comparable with the standard antibiotic. The
      synthesized compounds have shown antiproliferative activity against the human
      breast cancer cell lines MDA-MB231 by intermitting the regular pathway of
      ribonucleotidereductase. 

PMID- 23871985
TI  - Inhibition of human platelet aggregation by eosinophils.
AB  - AIMS: The relationship between the activity of eosinophils and platelets has been
      observed in recent decades by many scientists. These observations include
      increased numbers of eosinophils associated with platelet disorders, including
      changes in the coagulation cascade and platelet aggregation. Based on these
      observations, the interaction between eosinophils and platelets in platelet
      aggregation was analyze. MAIN METHODS: Human platelets were incubated with
      eosinophil cytosolic fraction, promyelocytic human HL-60 clone 15 cell lineage,
      and eosinophil cationic protein (ECP). Platelet rich plasma (PRP) aggregation was
      induced by adenosine diphosphate, platelet activating factor, arachidonic acid,
      and collagen, and washed platelets (WP) were activated by thrombin. KEY FINDINGS:
      Aggregation induced by all agonists was dose dependently inhibited by eosinophil
      cytosolic fraction. This inhibition was only partially reversed by previous
      incubation of the eosinophils with l-Nitro-Arginine-Methyl-Ester (l-NAME).
      Previous incubation with indomethacin did not prevent the cytosolic fraction
      induced inhibition. The separation of eosinophil cytosolic fraction by gel
      filtration on Sephadex G-75 showed that the inhibitory activity was concentrated
      in the lower molecular weight fraction. HL-60 clone 15 cells differentiated into
      eosinophils for 5 and 7 day were able to inhibit platelet aggregation. The ECP
      protein inhibited the platelet aggregation on PRP and WP. This inhibition was
      more evident in WP, and the citotoxicity MTT assay proved the viability of tested
      platelets, showing that the observed inhibition by the ECP protein does not occur
      simply by cell death. SIGNIFICANCE: Our results indicate that eosinophils play a
      fundamental role in platelet aggregation inhibition.

PMID- 23871986
TI  - Neonatal treatment with monosodium glutamate lastingly facilitates spreading
      depression in the rat cortex.
AB  - AIMS: Monosodium glutamate (MSG) is a neuroexcitatory amino acid used in human
      food to enhance flavor. MSG can affect the morphological and electrophysiological
      organization of the brain. This effect is more severe during brain development.
      Here, we investigated the electrophysiological and morphological effects of MSG
      in the developing rat brain by characterizing changes in the excitability-related
      phenomenon of cortical spreading depression (CSD) and microglial reaction. MAIN
      METHODS: From postnatal days 1-14, Wistar rat pups received 2 or 4 g/kg MSG
      (groups MSG-2 and MSG-4, respectively; n=9 in each group), saline (n=10) or no
      treatment (naive group; n=5) every other day. At 45-60 days, CSD was recorded on
      two cortical points for 4h. The CSD parameters velocity, and amplitude and
      duration of the negative potential change were calculated. Fixative-perfused
      brain sections were immunolabeled with anti-IBA-1 antibodies to identify and
      quantify cortical microglia. KEY FINDINGS: MSG-4 rats presented significantly
      higher velocities (4.59 +/- 0.34 mm/min) than the controls (saline, 3.84 +/-
      0.20mm/min; naive, 3.71 +/- 0.8mm/min) and MSG-2 group (3.75 +/- 0.10mm/min). The
      amplitude (8.8 +/- 2.2 to 11.2 +/- 1.9 mV) and duration (58.2 +/- 7.1 to 73.6 +/-
      6.0s) of the negative slow potential shift was similar in all groups. MSG
      treatment dose-dependently increased the microglial immunolabeling. SIGNIFICANCE:
      The results demonstrate a novel, dose-dependent action of MSG in the developing
      brain, characterized by acceleration of CSD and significant microglial reaction
      in the cerebral cortex. The CSD effect indicates that MSG can influence cortical
      excitability, during brain development, as evaluated by CSD acceleration. Data
      suggest caution when consuming MSG, especially in developing organisms.

PMID- 23871987
TI  - On-treatment C-reactive protein and HDL cholesterol levels in patients at
      intermediate cardiovascular risk: impact on carotid intima-media thickness.
AB  - AIMS: Statin therapy is followed by reductions in carotid intima-media thickness
      (CIMT) and C-reactive protein (CRP) levels, but a significant number of treated
      patients still have increased CIMT. We investigated whether on-treatment levels
      of CRP are associated with CIMT in hypercholesterolemic patients receiving statin
      therapy. The influence of blood pressure and anti-hypertensive therapy on the
      association between CRP and CIMT was evaluated. MAIN METHODS: The assessment of
      cardiovascular risk factors, CRP and CIMT, was performed in a cross-sectional
      study of 240 hypercholesterolemic patients at intermediate cardiovascular risk
      under statin therapy; 125 patients received only a statin (statin group) and 115
      also anti-hypertensive therapy (combined therapy group). KEY FINDINGS:
      Logarithmically transformed CRP (beta=0.17, p=0.01) and HDL cholesterol levels
      (beta=-0.27, p<0.001) were correlates of CIMT, irrespective of confounders. High
      CRP levels (>3mg/L) were associated with a 2.7-fold increased risk of having high
      CIMT (>1.25mm). High CIMT was present in a high percentage of patients not at
      target for cholesterol and blood pressure levels (61%). Patients in the statin
      group had lower Framingham risk and CIMT than those in the combined therapy
      group. In the statin group, logarithmically transformed CRP (beta=0.28, p=0.004)
      and HDL cholesterol (beta=-0.21, p=0.03) were associated with CIMT. In the
      combined therapy group, HDL cholesterol was the only significant CIMT correlate
      (beta=-0.33, p=0.001). SIGNIFICANCE: On-treatment CRP and HDL cholesterol levels
      are associated with CIMT among hypercholesterolemic patients under statin
      therapy. In patients receiving both statin and anti-hypertensive therapy, HDL
      cholesterol remains the main covariate of CIMT.

PMID- 23871989
TI  - Dihydrotanshinone induces p53-independent but ROS-dependent apoptosis in colon
      cancer cells.
AB  - AIMS: The therapeutic potential of various tanshinones was examined and compared
      for their anti-cancer activities on colon cancer cells. The role of ROS
      generation in the pro-apoptotic activity of dihydrotanshinone (DHTS) was further
      studied. MAIN METHODS: Cell viability was determined by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis and
      poly-ADP-ribose-polymerase (PARP) cleavage were respectively measured by flow
      cytometer and Western blot. Changes of mitochondrial membrane potential (MMP),
      mitochondrial ROS (mitoROS) and total ROS were determined by confocal system
      under an inverted microscope. KEY FINDINGS: Among the different tanshinones
      examined, DHTS produced the most potent anti-cancer effect. DHTS induced a
      selective cytotoxicity and apoptosis in both HCT116 p53(-/-) and HCT116 p53(+/+)
      colon cancer cells. A time- and concentration-dependent PARP cleavage further
      confirmed the apoptotic activity. In this regard, it was found DHTS provoked
      mitochondrial dysfunction in the early stage by decreasing MMP and mitoROS
      levels. This was followed by a time-dependent increase in intracellular ROS
      generation. Pretreatment with N-acetyl-l-cysteine (NAC) or catalase-PEG, the free
      radical scavengers, reduced apoptotic cell death. From these findings, it seems
      that leakage of ROS from mitochondria into cytosol by DHTS represents the major
      contributory factor leading to cell death in colon cancer cells. SIGNIFICANCE: We
      report for the first time that DHTS induces apoptosis in colon cancer cells
      through a p53-independent pathway. Disturbance of ROS generation at the oxidative
      phosphorylation (OXPHOS) complex in mitochondria followed by the decrease of MMP
      and increase of intracellular ROS accumulation are suggested to be involved in
      the pro-apoptotic activity of DHTS.

PMID- 23871990
TI  - Effects of asiaticoside on levels of podocyte cytoskeletal proteins and renal
      slit diaphragm proteins in adriamycin-induced rat nephropathy.
AB  - AIMS: Centella asiatica has been used to treat kidney diseases in Chinese
      traditional medicine. Asiaticoside (an extraction of C. asiatica) exerts a
      variety of pharmacological effects including immunomodulatory and anti
      inflammatory functions. However, the mechanism of asiaticoside in the treatment
      of renal diseases remains largely unknown. This study investigated the molecular
      mechanism of asiaticoside in treating adriamycin-induced nephropathy of rats.
      MAIN METHODS: Sixty-two SD male rats were randomly divided into normal control
      group (n=12) and nephropathy group (n=50). Except for the normal control group,
      rats were injected with adriamycin (6mg/kg) via the tail vein to induce
      nephropathy. Adriamycin induced nephropathic rats were divided into untreated
      group, prednisone group (25mg/kg), and asiaticoside groups with various dosages
      (8, 16 and 32mg/kg). Samples of urine and serum, tissue of kidney were collected
      for analysis after treatments for four weeks. Morphological changes were
      evaluated under light microscope and electron microscope. Synaptopodin, desmin,
      nephrin and podocin mRNA and protein were determined by RT-PCR and Western
      blotting. KEY FINDINGS: Compared to the untreated nephropathy group, asiaticoside
      treatment mitigated histological damages, decreased 24-hour urine protein
      excretion and total cholesterol, increased serum albumin. Asiaticoside treatment
      increased the mRNA and protein levels of synaptopodin, nephrin and podocin in a
      dose-dependent manner. Furthermore, asiaticoside treatment decreased the mRNA and
      protein levels of desmin. SIGNIFICANCE: Asiaticoside can mitigate adriamycin
      induced nephropathy in rats, which is associated with the increase in
      synaptopodin, nephrin and podocin gene expression, and the decrease in desmin
      gene expression.

PMID- 23871991
TI  - Menopausal hormone therapy and breast cancer.
AB  - Observational and randomized controlled trial data have extensively examined the
      relationship between menopausal hormone therapy (MHT) and risk of developing
      breast cancer. A highly influential study from the Women's Health Initiative
      (WHI) in 2002 reported that a MHT regimen of conjugated equine estrogens and
      medroxyprogesterone acetate increased the risk of breast cancer by 26%. Later
      reports from the WHI indicated that a MHT regimen with conjugated equine
      estrogens alone decreased the risk of breast cancer by 23%. Critical re
      examination of the WHI study noted that the average participant age was 63, that
      few women had symptoms, and that the WHI results might not apply to younger,
      symptomatic women shortly after menopause. Since the original publications,
      several post hoc analyses and observational studies have stimulated
      reconsideration of the WHI findings. Emphasis has been directed toward risks in
      younger women just entering the menopause, the subgroup who are most likely to be
      considering MHT use. The goal of this treatise is to integrate available
      mechanistic and clinical information related to the use of estrogen alone or
      estrogen plus a progestogen for five years or less. These data suggest that
      estrogen alone neither decreases nor increases risk in younger women initiating
      therapy close to the time of menopause but decreases risk in older women. Both
      younger and older women experience an excess risk with estrogen plus a
      progestogen. The attributable risk in younger women is less in those with a low
      underlying Gail Model risk score. Effects of MHT on risk largely reflect actions
      on pre-existing, occult, undiagnosed breast cancers. Tumor kinetic models suggest
      that the pro-proliferative effects of estrogen plus a progestogen on occult
      tumors provide a mechanistic explanation for the increased risk with this
      therapy. Pro-apoptotic effects of estrogen alone may explain the reduction of
      breast cancer in women starting this therapy at an average age of 63 as reported
      in the WHI study. This article is part of a Special Issue entitled 'Menopause'. 

PMID- 23871988
TI  - Potential benefits of green tea polyphenol EGCG in the prevention and treatment
      of vascular inflammation in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints in
      which systemic overproduction of pro-inflammatory cytokines such as interleukin-6
      (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may accelerate cardiovascular
      (CV) complications. Synovial inflammation in RA spreads systemically and
      transforms silently into chronic inflammation manifested by increased cytokine
      release and abnormally high levels of acute reactive proteins (ARPs) such as C
      reactive protein (CRP), suggesting inflammation as a connecting link between RA
      and CV dysfunction. While the treatment to improve CV function in RA patients is
      being validated, it is timely to propose and test two-pronged therapies that
      ameliorate arthritis concomitant to improving CV functions. In this review, we
      summarized the pre-clinical and clinical studies validating the cardiovascular
      and anti-rheumatic activities of epigallocatechin-3 gallate (EGCG), a potent anti
      inflammatory molecule found in green tea. The review also draws many parallels
      that have emerged between the paradigm of cytokine-driven inflammation in the
      pathogenesis of RA and its CV complications. Finally, based on extensive clinical
      evidence of the 'synovial inflammation-systemic inflammation' link and the
      benefits of EGCG in regulating these two pathologies via common driving factors,
      authors put forward an argument that EGCG may be tested for its potential CV
      benefit along with anti-rheumatic activity in animal models of human RA. 

PMID- 23871992
TI  - Unlocking the secrets of the gatekeeper: methods for stabilizing and
      crystallizing GPCRs.
AB  - G-protein coupled receptors (GPCRs) are integral membrane cell surface receptors
      with key roles in mediating the cellular responses to a wide range of
      biologically relevant molecules including hormones, neurotransmitters and
      importantly the majority of currently available drugs. The first high-resolution,
      X-ray crystallographic structure of a GPCR, that of rhodopsin, was obtained in
      2000. It took a further seven years for the next structure, that of the beta2
      adrenergic receptor. Remarkably, at the time of writing, there have been an
      astonishing 18 further independent high-resolution GPCR structures published in
      the last five years (overall total of 68 structures in different conformations or
      bound to different ligands). Of particular note is the recent structure of the
      beta2 adrenergic receptor in complex with its cognate heterotrimeric G-protein
      revealing for the first time molecular details of the interaction between a GPCR
      and the complete G-protein. Together these structures have provided unprecedented
      detail into the mechanism of action of these incredibly important proteins. This
      review describes several key methodological advances that have made such
      extraordinarily fast progress possible. 

PMID- 23871993
TI  - Competitive binding of nile red between lipids and beta-cyclodextrin.
AB  - Fluorometric measurements are exploited to explore the binding interactions of
      nile red (NR) with anionic lipid dimyristoyl-L-alpha-phosphatidylglycerol (DMPG),
      zwitterionic lipid dimyristoyl-L-alpha-phosphatidylcholine (DMPC) as well as
      neutral cyclic oligosaccharide beta-cyclodextrin (beta-CD) solutions. The binding
      constants are found to be quite high and comparable (within a factor of five).
      Series of spectral techniques like steady state fluorescence and fluorescence
      anisotropy study, micropolarity study, quenching study and time resolved
      experiments reveal that the addition of beta-CD to the probe-lipid complexes
      results in weakening of the lipid-probe interaction and formation of probe-beta
      CD inclusion complexes leading to the removal of some of the probe (NR) molecules
      from the lipid environments. The extent of removal of NR is, however, more from
      DMPG than DMPC lipid. The phenomena are explained from the concept of competitive
      binding of the probe between the lipids and beta-CD. Since lipids are the
      principal constituents of the cell walls, the work might make a foundation for
      the possible removal of excess of molecules like nile red adsorbed on the cell
      walls. 

PMID- 23871994
TI  - Validity of a portable glucose, total cholesterol, and triglycerides multi
      analyzer in adults.
AB  - This study investigated the accuracy and precision of the Accutrend Plus system
      to determine blood glucose, total cholesterol, and plasma triglycerides in adults
      and evaluated its efficiency in measuring these blood variables. The sample
      consisted of 53 subjects (>= 18 years). For blood variable laboratory
      determination, venous blood samples were collected and processed in a Labmax 240
      analyzer. To measure blood variables with the Accutrend Plus system, samples of
      capillary blood were collected. In the analysis, the following tests were
      included: Wilcoxon and Student's t-tests for paired samples, Lin's concordance
      coefficient, Bland-Altman method, receiver operating characteristic curve,
      McNemar test, and k statistics. The results show that the Accutrend Plus system
      provided significantly higher values (p <= .05) of glucose and triglycerides but
      not of total cholesterol (p > .05) as compared to the values determined in the
      laboratory. However, the system showed good reproducibility (Lin's coefficient:
      glucose = .958, triglycerides = .992, total cholesterol = .940) and high
      concordance with the laboratory method (Lin's coefficient: glucose = .952,
      triglycerides = .990, total cholesterol = .944) and high sensitivity (glucose =
      80.0%, triglycerides = 90.5%, total cholesterol = 84.4%) and specificity (glucose
      = 100.0%, triglycerides = 96.9%, total cholesterol = 95.2%) in the discrimination
      of high values of the three blood variables analyzed. It could be concluded that
      despite the tendency to overestimate glucose and triglyceride levels, a portable
      multi-analyzer is a valid alternative for the monitoring of metabolic disorders
      and cardiovascular risk factors.

PMID- 23871995
TI  - A high-throughput assay for screening L- or D-amino acid specific
      aminotransferase mutant libraries.
AB  - Aminotransferases are pyridoxal phosphate-dependent enzymes whose potential for
      the biocatalytic production of enantiopure amino acids is increasingly
      recognized. Because of this, there is a growing interest in engineering them to
      alter their substrate specificity and to increase their catalytic activity. Here,
      we report the development of a high-throughput assay for screening alpha
      ketoglutarate-dependent aminotransferase mutant libraries. To achieve this, we
      exploited the L-glutamate dehydrogenase coupled assay that has previously been
      shown to allow for aminotransferase activity to be monitored in vitro. We adapted
      this assay to allow screening of mutant libraries of either L- or D-amino acid
      specific aminotransferases in a continuous fashion. This assay requiring
      clarified cell lysates is reproducible, rapid, and sensitive because it allowed
      for the identification of a catalytically active mutant of Bacillus sp. YM-1 D
      amino acid aminotransferase displaying a decrease in k(cat)/K(M) of more than two
      orders of magnitude. In addition, this assay allowed us to discover a mutant of
      Escherichia coli branched-chain amino acid aminotransferase, F36W, which is
      approximately 60-fold more specific toward the natural substrate L-leucine than L
      phenylalanine as compared with wild type. This result demonstrates the potential
      of our assay for the discovery of mutant aminotransferases displaying altered
      substrate specificity, an important goal of enzyme engineering.

PMID- 23871996
TI  - An isothermal absorptiometric assay for viable microbes using the redox color
      indicator 2,6-dichlorophenolindophenol.
AB  - A simple and rapid isothermal absorptiometric assay for detection of viable
      microbes using the redox color indicator 2,6-dichlorophenolindophenol (DCPIP) was
      studied. The absorbance of DCPIP decreased at 600 nm because of a redox reaction
      occurring between DCPIP and the surface membrane of viable microbes and was
      inversely proportional to the viable cell density. The redox reaction was found
      not only with bacteria, but also with yeast and a mixture of bacteria and yeast.
      In this assay, the influence of light scattering and absorption caused by
      microbial cells and coexisting substances in the sample was excluded by a time
      difference method. The assay required only 10 min for one incubation mixture, and
      highly repeatable results from three consecutive measurements were obtained by
      isothermal incubation for specific times at 30  degrees C using a thermostable
      three-cuvette-stir system. Thus, the cell density of microbial cell suspensions
      or growth medium was successfully determined, and a practical lower detection
      limit for food inspection was obtained at 104-106 cfu/ml. Single-cell effects on
      DCPIP reduction were evaluated and compared between species. Consequently, this
      assay is expected to be a useful tool for the rapid measurement of viable
      microbes as a preliminary assay for the Hazard Analysis Critical Control Point
      program.

PMID- 23871997
TI  - A DNA immunoprecipitation assay used in quantitative detection of in vitro DNA
      protein complex binding.
AB  - To begin gene transcription, several transcription factors must bind to specific
      DNA sequences to form a complex via DNA-protein interactions. We established an
      in vitro method for specific and sensitive analyses of DNA-protein interactions
      based on a DNA immunoprecipitation (DIP) method. We verified the accuracy and
      efficiency of the DIP assay in quantitatively measuring DNA-protein binding using
      transcription factor CP2c as a model. With our DIP assay, we could detect
      specific interactions within a DNA-CP2c complex, with reproducible and
      quantitative binding values. In addition, we were able to effectively measure the
      changes in DNA-CP2c binding by the addition of a small molecule, FQI1 (factor
      quinolinone inhibitor 1), previously identified as a specific inhibitor of this
      binding. To identify a new regulator of DNA-CP2c binding, we analyzed several
      CP2c binding peptides and found that only one class of peptide severely inhibits
      DNA-CP2c binding. These data show that our DIP assay is very useful in
      quantitatively detecting the binding dynamics of DNA-protein complex. Because DNA
      protein interaction is very dynamic in different cellular environments, our assay
      can be applied to the detection of active transcription factors, including
      promoter occupancy in normal and disease conditions. Moreover, it may be used to
      develop a targeted regulator of specific DNA-protein interaction. 

PMID- 23871998
TI  - Label-free high-throughput assays to screen and characterize novel lactate
      dehydrogenase inhibitors.
AB  - Catalytic turnover of pyruvate to lactate by lactate dehydrogenase (LDH) is
      critical in maintaining an intracellular nicotinamide adenine dinucleotide (NAD+)
      pool for continuous fueling of the glycolytic pathway. In this article, we
      describe two label-free high-throughput assays (a kinetic assay detecting the
      intrinsic reduced nicotinamide adenine dinucleotide (NADH) fluorescence and a
      mass spectrometric assay monitoring the conversion of pyruvate to lactate) that
      were designed to effectively identify LDH inhibitors, characterize their
      different mechanisms of action, and minimize potential false positives from a
      small molecule compound library screen. Using a fluorescence kinetic image-based
      reader capable of detecting NADH fluorescence in the ultra-high-throughput
      screening (uHTS) work flow, the enzyme activity was measured as the rate of NADH
      conversion to NAD+. Interference with NADH fluorescence by library compounds was
      readily identified during the primary screen. The mass spectrometric assay
      quantitated the lactate and pyruvate levels simultaneously. The multiple reaction
      monitoring mass spectrometric method accurately detected each of the two small
      organic acid molecules in the reaction mixture. With robust Z' scores of more
      than 0.7, these two high-throughput assays for LDH are both label free and
      complementary to each other in the HTS workflow by monitoring the activities of
      the compounds on each half of the LDH redox reaction.

PMID- 23871999
TI  - Development of a multiple-bile-ion-sensing membrane electrode.
AB  - A multiple-bile-ion-sensing polyvinyl chloride-based membrane electrode capable
      of monitoring any of the three common bile ions in humans, namely, cholate,
      deoxycholate, and chenodeoxycholate, was developed and characterized. Compared to
      single-bile-ion-sensing electrodes, it showed a sub-Nernstian response. All other
      electrode properties were, however, similar, making this a successful replacement
      for three individual electrodes. With appropriate conditioning, this electrode
      could repeatedly change selectivity without losing membrane activity. It was
      reproducible, was stable for 5 months, had low response time, and could be used
      to measure critical micelle concentrations. The lower limit of detection was 10
      nM. Selectivity coefficients for various anions with respect to bile ions more or
      less followed the Hoffmeister series. Plots of R ((Nernst equivalent of slope in
      the presence of primary ion and a fixed amount of interfering ion)/(slope in the
      presence of only the primary ion)) vs square root of ionic strength for an
      interfering ion were linear. One major application of this electrode is its use
      in kinetics. We have tested its ability to monitor continuously changing bile ion
      concentrations during their interactions with a biocompatible polymer,
      polyethylene glycol (6000), and determined rate constants.

PMID- 23872000
TI  - DNA extraction protocol for rapid PCR detection of pathogenic bacteria.
AB  - Twelve reagents were evaluated to develop a direct DNA extraction method suitable
      for PCR detection of foodborne bacterial pathogens. Many reagents exhibited
      strong PCR inhibition, requiring significant dilution of the extract with a
      corresponding reduction in sensitivity. Most reagents also exhibited much lower
      recovery of DNA from the gram-positive test organism (Listeria monocytogenes)
      than from the gram-negative organism (Escherichia coli O157:H7), preventing
      unbiased detection and quantitation of both organisms. The 5* HotSHOT+Tween
      reagent exhibited minimal inhibition and high extraction efficiency for both test
      organisms, providing a 15-min single-tube DNA-extraction protocol suitable for
      highly sensitive quantitative PCR assays. 

PMID- 23872001
TI  - Pyroglutamyl apelin-13 identified as the major apelin isoform in human plasma.
AB  - Apelin is emerging as an important hormone regulator of cardiovascular
      homoeostasis and an important biomarker for heart failure. Apelin concentrations
      have historically been measured by immunoassays; however, reported apelin
      concentrations measured in healthy volunteers show a large disparity from a few
      picograms per milliliter (pg/ml) to several nanograms per milliliter (ng/ml).
      Apelin exists in several isoforms ranging in size from 12 to 36 residues, and
      immunoassays generally cannot distinguish the specific forms present. In this
      study, an optimized method for enriching apelin peptides with cation-exchange
      beads followed with mass spectrometry analysis is presented. Apelin peptides are
      labile in plasma at physiological conditions; however, by lowering the plasma pH
      to 4.5, the recovery of apelin peptides can be increased significantly. Through
      optimizing the cation-exchange extraction process, we improved the lower limit of
      detection for most of the apelin peptides monitored to a few pg/ml. Using the
      improved method, we detected pyroglutamyl apelin-13 [(pyr)apelin-13] as the major
      apelin isoform present in plasma from several healthy volunteers at
      concentrations ranging from 7.7 to 23.3pg/ml. 

PMID- 23872002
TI  - Preparation of 2-nitro-5-thiobenzoate for the routine determination of reagent
      hypochlorous acid concentrations.
AB  - Solutions of hypochlorous acid (HOCl) decay over time. This decay indicates the
      necessity for methods and reagents for the routine measurement of this oxidant. 2
      Nitro-5-thiobenzoate is commonly used to measure HOCl concentrations. This
      article describes a method for the preparation of 2-nitro-5-thiobenzoate that is
      stable for at least 3 months. This method relies on the partial rather than full
      reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) and the resulting equilibrium
      between the substrate and the product.

PMID- 23872003
TI  - Stopped-flow DNA polymerase assay by continuous monitoring of dNTP incorporation
      by fluorescence.
AB  - DNA polymerase activity was measured by a stopped-flow assay that monitors
      polymerase extension using an intercalating dye. Double-stranded DNA formation
      during extension of a hairpin substrate was monitored at 75 degrees C for 2 min.
      Rates were determined in nucleotides per second per molecule of polymerase (nt/s)
      and were linear with time and polymerase concentration from 1 to 50 nM. The
      concentrations of 15 available polymerases were quantified and their extension
      rates determined in 50 mM Tris, pH 8.3, 0.5 mg/ml BSA, 2 mM MgCl2, and 200 MUM
      each dNTP as well as their commercially recommended buffers. Native Taq
      polymerases had similar extension rates of 10-45 nt/s. Three alternative
      polymerases showed faster speeds, including KOD (76 nt/s), Klentaq I (101 nt/s),
      and KAPA2G (155 nt/s). Fusion polymerases including Herculase II and Phusion were
      relatively slow (3-13 nt/s). The pH optimum for Klentaq extension was between 8.5
      and 8.7 with no effect of Tris concentration. Activity was directly correlated to
      the MgCl2 concentration and inversely correlated to the KCl concentration. This
      continuous assay is relevant to PCR and provides accurate measurement of
      polymerase activity using a defined template without the need of radiolabeled
      substrates.

PMID- 23872004
TI  - A derivatization method for the simultaneous detection of glucosinolates and
      isothiocyanates in biological samples.
AB  - Various analytical methods have been established to quantify isothiocyanates
      (ITCs) that derive from glucosinolate hydrolysis. However, to date there is no
      valid method applicable to pharmacokinetic studies that detects both
      glucosinolates and ITCs. A specific derivatization procedure was developed for
      the determination of ITCs based on the formation of a stable N-(tert
      butoxycarbonyl)-L-cysteine methyl ester derivative, which can be measured by high
      performance liquid chromatography with ultraviolet detection after extraction
      with ethylacetate. The novel method, which is also applicable to the indirect
      determination of glucosinolates after their hydrolysis by myrosinase, was
      established for the simultaneous determination of glucoraphanin and sulforaphane.
      By derivatization, the sensitivity of ITC detection was increased 2.5-fold.
      Analytical recoveries from urine and plasma were greater than 75% and from feces
      were approximately 50%. The method showed intra- and interday variations of less
      than 11 and 13%, respectively. Applicability of the method was demonstrated in
      mice that received various doses of glucoraphanin or that were fed a
      glucoraphanin-rich diet. Besides glucoraphanin and sulforaphane, glucoerucin and
      erucin were detected in urine and feces of mice. The novel method provides an
      essential tool for the analysis of bioactive glucosinolates and their hydrolysis
      products and, thus, will contribute to the elucidation of their bioavailability.

PMID- 23872005
TI  - SYBR green dye-based probe-free SNP genotyping: introduction of T-Plex real-time
      PCR assay.
AB  - Single-nucleotide polymorphism (SNP) genotyping is widely used in genetic
      association studies to characterize genetic factors underlying inherited traits.
      Despite many recent advances in high-throughput SNP genotyping, inexpensive and
      flexible methods with reasonable throughput levels are still needed. Real-time
      PCR methods for discovering and genotyping SNPs are becoming increasingly
      important in various fields of biology. In this study, we introduce a new, single
      tube strategy that combines the tetra-primer ARMS PCR assay, SYBR Green I-based
      real-time PCR, and melting-point analysis with primer design strategies to detect
      the SNP of interest. This assay, T-Plex real-time PCR, is based on the T(m)
      discrimination of the amplified allele-specific amplicons in a single tube. The
      specificity, sensitivity, and robustness of the assay were evaluated for common
      mutations in the FV, PII, MTHFR, and FGFR3 genes. We believe that T-Plex real
      time PCR would be a useful alternative for either individual genotyping requests
      or large epidemiological studies.

PMID- 23872006
TI  - An automated robotic platform for rapid profiling oligosaccharide analysis of
      monoclonal antibodies directly from cell culture.
AB  - Oligosaccharides attached to Asn297 in each of the CH2 domains of monoclonal
      antibodies play an important role in antibody effector functions by modulating
      the affinity of interaction with Fc receptors displayed on cells of the innate
      immune system. Rapid, detailed, and quantitative N-glycan analysis is required at
      all stages of bioprocess development to ensure the safety and efficacy of the
      therapeutic. The high sample numbers generated during quality by design (QbD) and
      process analytical technology (PAT) create a demand for high-performance, high
      throughput analytical technologies for comprehensive oligosaccharide analysis. We
      have developed an automated 96-well plate-based sample preparation platform for
      high-throughput N-glycan analysis using a liquid handling robotic system.
      Complete process automation includes monoclonal antibody (mAb) purification
      directly from bioreactor media, glycan release, fluorescent labeling,
      purification, and subsequent ultra-performance liquid chromatography (UPLC)
      analysis. The entire sample preparation and commencement of analysis is achieved
      within a 5-h timeframe. The automated sample preparation platform can easily be
      interfaced with other downstream analytical technologies, including mass
      spectrometry (MS) and capillary electrophoresis (CE), for rapid characterization
      of oligosaccharides present on therapeutic antibodies. 

PMID- 23872007
TI  - Development of buffers for fast semidry transfer of proteins.
AB  - Western blot is an extensively used method for protein detection in cell biology.
      To optimize this procedure, here we examined a panel of buffers for their ability
      to efficiently transfer proteins from SDS-polyacrylamide gels onto nitrocellulose
      membranes in a short 12-min period, designated here as fast semidry transfer. Our
      results show for the first time that HEPES- and HEPPS/EPPS-based buffers
      represent the most efficient buffers for fast semidry transfer. 

PMID- 23872008
TI  - Measuring the antioxidant capacity of blood plasma using potentiometry.
AB  - The use of potentiometry to measure plasma antioxidant capacity to contribute to
      oxidative stress evaluation is presented. In this assay, plasma (n=60) diluted
      (0.3 to 1 ml) in phosphate buffer, pH 7.4, NaCl 9%, was submitted to
      potentiometry. A platinum wire was the working electrode and saturated calomel
      the reference. The results are presented as the difference between sample and
      buffer potential (DeltaE). DeltaE presented a good inverse correlation with added
      increasing concentrations of ascorbate (2.5-75 MUmol/L; R=-0.99), urate (9.0-150
      MUmol/L; R=-0.99), and bilirubin (0.78-13 MUmol/L; R=-0.99). Increase in the
      antioxidant capacity decreased DeltaE. Depletion of the antioxidant capacity by
      tert-butylhydroperoxide (6.5-50 MUmol/L) presented a direct correlation (0.97)
      with DeltaE. Furthermore, DeltaE presented an inverse correlation (R=-0.99) with
      increased antioxidant capacity of plasma (FRAP) induced by the addition of
      ascorbate (2.5-75 MUmol/L). The response of the potentiometric method proved be
      adequate for measuring the plasma antioxidant depletion induced by acute
      exhaustive exercise in rats (control, n=15; exercised, n=15). This exercise
      decreased the concentration of urate (p<0.05), decreased FRAP (p<0.5), increased
      TBARS (p<0.5), and decreased the potentiometer sensor response (p=6.5*10-3).
      These results demonstrate the adequacy of potentiometry for evaluating the
      antioxidant capacity of blood plasma samples.

PMID- 23872009
TI  - Electrogenerated chemiluminescence of novel TiO2/CdS nanocomposites for sensitive
      assays of cancer cells.
AB  - A novel TiO2/CdS nanocomposite was prepared and used to fabricate an
      electrochemiluminescence (ECL) biosensor for the detection of cancer cells for
      the first time. The nanocomposite exhibited a strong cathodic ECL signal. Folic
      acid for targeting cell membranes was bound to a TiO2/CdS/3
      aminopropyltriethoxysilane film, and specific recognition of folic acid to
      targeting cells was achieved, leading to a significant decrease in ECL intensity.
      The decrease in ECL signal was logarithmically related to the cell concentration
      in the range of 150-9600 cells mL(-1). The ECL biosensor could provide a
      sensitive, selective, and convenient approach for early and accurate detection of
      cancer cells.

PMID- 23872010
TI  - Rational design of a thrombin electrochemical aptasensor by conjugating two DNA
      aptamers with G-quadruplex halves.
AB  - A novel strategy for the fabrication of an electrochemical aptasensor is
      proposed; this strategy has been employed in this work to assay thrombin
      concentration. Two well-designed oligonucleotides were used as the core element.
      G-quadruplex-hemin complexes can be formed on the surface of the electrode to
      give a detectable signal only when thrombin is not bound to the aptamers. The
      detection limit of the biosensor has been lowered to 10nM. Moreover, since the
      electroactive probe is not required to be bound to the oligonucleotide, this
      strategy may integrate the advantages of being both label-free and cost
      effective. 

PMID- 23872011
TI  - Novel anti-cholinergics in COPD.
AB  - Anti-cholinergics have been considered the first-choice bronchodilator therapy in
      the routine management of stable COPD. Muscarinic cholinergic receptors are
      expressed on most cell types and mediate cellular signalling via the natural
      ligand, acetylcholine. Antagonising cholinergic receptors may not only result in
      bronchodilation, but also have associated localised activity. Until recently the
      licensed anti-cholinergics were limited to ipatropium bromide, oxitropium bromide
      and tiotropium bromide; the latter being the only once-daily anti-cholinergic.
      With the patents expired or due to expire shortly several companies have
      reinitiated efforts to develop safer, long-acting agents potentially improving
      concordance and pharmaceutical marketing opportunities. The present article
      reviews a number of novel anti-cholinergics that have been recently licensed and
      those undergoing development, some in innovative delivery devices. 

PMID- 23872012
TI  - Chitosans for delivery of nucleic acids.
AB  - Alternatives to efficient viral vectors in gene therapy are desired because of
      their poor safety profiles. Chitosan is a promising non-viral nucleotide delivery
      vector because of its biocompatibility, biodegradability, low immunogenicity and
      ease of manufacturing. Since the transfection efficiency of chitosan polyplexes
      is relatively low compared to viral counterparts, there is an impetus to gain a
      better understanding of the structure-performance relationship. Recent progress
      in preparation and characterisation has enabled coupling analysis of chitosans
      structural parameters that has led to increased TE by tailoring of chitosan's
      structure. In this review, we summarize the recent advances that have lead to a
      more rational design of chitosan polyplexes. We present an integrated review of
      all major areas of chitosan-based transfection, including preparation, chitosan
      and polyplexes physicochemical characterisation, in vitro and in vivo assessment.
      In each, we present the obstacles to efficient transfection and the strategies
      adopted over time to surmount these impediments. 

PMID- 23872013
TI  - Synthesis, growth and characterization of a nonlinear optical crystal: Bis l
      proline hydrogen nitrate.
AB  - The single crystals of bis l-proline hydrogen nitrate (BLPHN) belonging to non
      centrosymmetric space group were successfully grown by the slow evaporation
      solution growth technique. The BLPHN crystals of size 10*7*3mm(3) were obtained
      in 35days. Initially, the solubility tests were carried out for two solvents such
      as deionized water and mixed of deionized water-acetone. Among the two solvents,
      the solubility of BLPHN was found to be the highest in deionized water, so
      crystallization of BLPHN was done from its aqueous solution. As grown, crystals
      were characterized by single crystal X-ray diffraction studies and optical
      transmission spectral studies. Infrared spectroscopy, thermo gravimetric analysis
      and differential thermal analysis measurements were performed to study the
      molecular vibration and thermal behavior of the grown BLPHN crystals. Nonlinear
      optical (NLO) behavior of BLPHN crystal was studied by Kurtz and Perry powder
      method. 

PMID- 23872014
TI  - Host-guest inclusion complex of propafenone hydrochloride with alpha- and beta
      cyclodextrins: spectral and molecular modeling studies.
AB  - Host-guest inclusion complexes of cyclodextrins (CDs) with a potential
      cardiovascular drug propafenone hydrochloride (PFO), were prepared and
      characterized using absorption, fluorescence, time-resolved fluorescence, SEM, FT
      IR, DSC, (1)H NMR, XRD and PM3 methods. The spectral studies suggested the phenyl
      ring along with carbonyl group is present inside of CD cavity. Solvent studies
      revealed that the normal Stokes shifted band originates from the locally excited
      state and the large Stokes shifted band occurs due to the emission from ICT.
      Nanosecond time-resolved studies indicated that PFO exhibits biexponential decay
      in water and triexponential decay in CD, indicating the formation of 1:1
      inclusion complex. The results from solid state studies showed important
      modifications in the physicochemical properties of free PFO. The DeltaH, DeltaG
      and DeltaS of the complexation process were determined and it was found that the
      complexation processes were spontaneous. Investigations of thermodynamic and
      electronic properties confirmed the stability of the inclusion complex. 

PMID- 23872015
TI  - Feasibility of using near infrared spectroscopy to detect and quantify an
      adulterant in high quality sandalwood oil.
AB  - Determination of the authenticity of essential oils has become more significant,
      in recent years, following some illegal adulteration and contamination scandals.
      The present investigative study focuses on the application of near infrared
      spectroscopy to detect sample authenticity and quantify economic adulteration of
      sandalwood oils. Several data pre-treatments are investigated for calibration and
      prediction using partial least square regression (PLSR). The quantitative data
      analysis is done using a new spectral approach - full spectrum or sequential
      spectrum. The optimum number of PLS components is obtained according to the
      lowest root mean square error of calibration (RMSEC=0.00009% v/v). The lowest
      root mean square error of prediction (RMSEP=0.00016% v/v) in the test set and the
      highest coefficient of determination (R(2)=0.99989) are used as the evaluation
      tools for the best model. A nonlinear method, locally weighted regression (LWR),
      is added to extract nonlinear information and to compare with the linear PLSR
      model. 

PMID- 23872016
TI  - Molecular structure of mercury(II) thiocyanate complexes based on DFT
      calculations and experimental UV-electron spectroscopy and Raman studies.
AB  - In this work, we report a combined experimental and theoretical study on
      molecular structure, vibrational and electronic spectra of [Hg(SCN)n](2-)(n)
      complexes (where n=2, 3, 4) in the aqueous solution. Molecular modeling of the
      mercury(II) complexes were done by the density functional theory (DFT) method
      using B3LYP functional with Stuttgart relativistic ECP 78MWB basis set for Hg and
      6-311++G(d,p) basis set for all other atoms. The effect of different solvation
      models with explicit (ligand) and/or implicit water environment upon its
      geometry, vibrational frequencies and UV spectrum have been studied. The
      influence of H2O/D2O exchange on the experimental and calculated vibrational
      frequencies of studied complexes has been established. The double-peak character
      of the nuHgS vibrational mode of the all analyzed mercury complexes and nuCN mode
      of [Hg(SCN)3H2O](-) complex, respectively, were proposed here for the first time.
      The formation of four-coordinated Hg(II) complexes with thiocyanate and (or)
      water ligands was verified. 

PMID- 23872017
TI  - Useful multivariate kinetic analysis: Size determination based on cystein-induced
      aggregation of gold nanoparticles.
AB  - This study describes spectrometric monitored kinetic processes to determine the
      size of citrate-capped Au nanoparticles (Au NPs) based on aggregation induced by
      l-cysteine (l-Cys) as a molecular linker. The Au NPs association process is
      thoroughly dependent on pH, concentration and size of nanoparticles. Size
      dependency of aggregation inspirits to determine the average diameters of Au NPs.
      For this aim the procedure is achieved in aqueous medium at pH 7 (phosphate
      buffer), and multivariate data including kinetic spectra of Au NPs are collected
      during aggregation process. Subsequently partial least squares (PLS) modeling is
      carried out analyzing the obtained data. The model is built on the basis of
      relation between the kinetics behavior of aggregation and different Au NPs sizes.
      Training the model was performed using latent variables (LVs) of the original
      data. The analytical performance of the model was characterized by relative
      standard error. The proposed method was applied to determination of size in
      unknown samples. The predicted sizes of unknown samples that obtained by the
      introduced method are interestingly in agreement with the sizes measured by
      Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS)
      measurement. 

PMID- 23872018
TI  - Vibrational spectral investigation and natural bond orbital analysis of
      pharmaceutical compound 7-Amino-2,4-dimethylquinolinium formate - DFT approach.
AB  - The molecular geometry, the normal mode frequencies and corresponding vibrational
      assignments, natural bond orbital analysis and the HOMO-LUMO analysis of 7-Amino
      2,4-dimethylquinolinium formate in the ground state were performed by B3LYP
      levels of theory using the 6-31G(d) basis set. The optimised bond lengths and
      bond angles are in good agreement with the X-ray data. The vibrational spectra of
      the title compound which is calculated by DFT method, reproduces vibrational wave
      numbers and intensities with an accuracy which allows reliable vibrational
      assignments. The possibility of N-H?O hydrogen bonding was identified using NBO
      analysis. Natural bond orbital analysis confirms the presence of intramolecular
      charge transfer and the hydrogen bonding interaction. 

PMID- 23872019
TI  - CdTe quantum dot as a fluorescence probe for vitamin B(12) in dosage form.
AB  - We here report the CdTe quantum dot (CdTe QDs)-based sensor for probing vitamin
      B12 derivatives in aqueous solution. In this paper, simple and sensitive
      fluorescence quenching measurements has been employed. The Stern-Volmer constant
      (KSV), quenching rate constant (kq) and binding constant (K) were rationalized
      from fluorescence quenching measurement. Furthermore, the fluorescence resonance
      energy transfer (FRET) mechanism was discussed. This method was applicable over
      the concentration ranging from 1 to 14MUg/mL (VB12) with correlation coefficient
      of 0.993. The limit of detection (LOD) of VB12 was found to be 0.15MUg/mL.
      Moreover, the present approach opens a simple pathway for developing cost
      effective, sensitive and selective QD-based fluorescence sensors/probes for
      biologically significant VB12 in pharmaceutical sample with mean recoveries in
      the range of 100-102.1%. 

PMID- 23872020
TI  - Spectroscopic properties and singlet oxygen production by the compound ethyl 3,12
      dioxopyran[3,2-a]xanthone-2-carboxylate.
AB  - The steady state and time resolved experiments together with absorption and
      emission spectroscopies and quantum chemical calculations have been employed to
      investigate spectroscopic properties of a xanthone-type compound (ethyl 3,12
      dioxopyran[3,2-a]xanthone-2-carboxylate). The spectroscopic data show good
      agreement with results obtained from quantum chemical calculations. Additionally,
      this compound shows expressive quantum efficiency for triplet population and a
      quantum efficiency of singlet oxygen generation very close to unity. Correlations
      between the nature of singlet and triplet excited states and spectroscopic
      properties were performed in order to understand the high quantum efficiency of
      singlet oxygen generation by this compound. 

PMID- 23872021
TI  - Evaluation of MidIR fibre optic reflectance: detection limit, reproducibility and
      binary mixture discrimination.
AB  - MidIR fibre optic reflectance (MidIR-FORS) is a promising analytical technique in
      the field of science conservation, especially because it is non-destructive.
      Another advantage of MidIR-FORS is that the obtained information is
      representative, as a large amount of spectral data can be collected. Although the
      technique has a high potential and is almost routinely applied, its quality
      parameters have not been thoroughly studied in the specific application of
      analysis of artistic materials. The objective of this study is to evaluate the
      instrumental capabilities of MidIR-FORS for the analysis of artwork materials in
      terms of detection limit, reproducibility, and mixture characterisation. The
      study has been focused on oil easel painting and several paints of known
      composition have been analysed. Paint layers include blue pigments not only
      because of their important role along art history, but also because their
      physical and spectroscopic characteristics allow a better evaluation of the MidIR
      FORS capabilities. The results of the analysis indicate that MidIR-FORS supplies
      a signal affected by different factors, such as the optical, morphological and
      physical properties of the surface, in addition to the composition of materials
      analysed. Consequently, the detection limits established are relatively high for
      artistic objects (Prussian blue - PB 2.1-6.5%; Phthalocyanine blue - Pht 6.3
      10.2%; synthetic Ultramarine blue - UM 12.1%) and may therefore lead to an
      incomplete description of the artwork. Reproducibility of the technique over time
      and across surface has been determined. The results show that the major sources
      of dispersion are the heterogeneity of the pigments distribution, physical
      features, and band shape distortions. The total dispersion is around 4% for the
      most intense bands (oil) and increases up to 26% when weak or overlapped bands
      are considered (PB, Pht, UM). The application of different pre-treatments (cutoff
      of fibres absorption, Savizky-Golay smoothing algorithm, polynomial baseline
      offset, Standard Normal Variate algorithm - SNV) to the raw spectra allows
      improving these results to maximum values of 15%. Finally, the capabilities of
      PCA and MidIR-FORS to discriminate between binary mixtures were tested. The
      results demonstrate that it is possible to differentiate mixtures depending on
      the range of concentration of their components, within specific limits of
      detection. 

PMID- 23872022
TI  - Binding analysis for interaction of diacetylcurcumin with beta-casein
      nanoparticles by using fluorescence spectroscopy and molecular docking
      calculations.
AB  - The interaction of diacetylcurcumin (DAC), as a novel synthetic derivative of
      curcumin, with bovine beta-casein (an abundant milk protein that is highly
      amphiphilic and self assembles into stable micellar nanoparticles in aqueous
      solution) was investigated using fluorescence quenching experiments, Forster
      energy transfer measurements and molecular docking calculations. The fluorescence
      quenching measurements revealed the presence of a single binding site on beta
      casein for DAC with the binding constant value equals to (4.40+/-0.03)*10(4)M(
      1). Forster energy transfer measurements suggested that the distance between
      bound DAC and Trp143 residue is higher than the respective critical distance,
      hence, the static quenching is more likely responsible for fluorescence quenching
      other than the mechanism of non-radiative energy transfer. Our results from
      molecular docking calculations indicated that binding of DAC to beta-casein
      predominantly occurred through hydrophobic contacts in the hydrophobic core of
      protein. Additionally, in vitro investigation of the cytotoxicity of free DAC and
      DAC-beta-casein complex in human breast cancer cell line MCF7 revealed the higher
      cytotoxic effect of DAC-beta-casein complex. 

PMID- 23872023
TI  - Dietary vitamin D deficiency in rats from middle to old age leads to elevated
      tyrosine nitration and proteomics changes in levels of key proteins in brain:
      implications for low vitamin D-dependent age-related cognitive decline.
AB  - In addition to the well-known effects of vitamin D (VitD) in maintaining bone
      health, there is increasing appreciation that this vitamin may serve important
      roles in other organs and tissues, including the brain. Given that VitD
      deficiency is especially widespread among the elderly, it is important to
      understand how the range of serum VitD levels that mimic those found in humans
      (from low to high) affects the brain during aging from middle age to old age. To
      address this issue, 27 male F344 rats were split into three groups and fed
      isocaloric diets containing low (100 IU/kg food), control (1000 IU/kg food), or
      high (10,000 IU/kg food) VitD beginning at middle age (12 months) and continued
      for a period of 4-5 months. We compared the effects of these dietary VitD
      manipulations on oxidative and nitrosative stress measures in posterior brain
      cortices. The low-VitD group showed global elevation of 3-nitrotyrosine compared
      to control and high-VitD-treated groups. Further investigation showed that this
      elevation may involve dysregulation of the nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) pathway and NF-kappaB-mediated
      transcription of inducible nitric oxide synthase (iNOS) as indicated by
      translocation of NF-kappaB to the nucleus and elevation of iNOS levels.
      Proteomics techniques were used to provide insight into potential mechanisms
      underlying these effects. Several brain proteins were found at significantly
      elevated levels in the low-VitD group compared to the control and high-VitD
      groups. Three of these proteins, 6-phosphofructokinase, triose phosphate
      isomerase, and pyruvate kinase, are involved directly in glycolysis. Two others,
      peroxiredoxin-3 and DJ-1/PARK7, have peroxidase activity and are found in
      mitochondria. Peptidyl-prolyl cis-trans isomerase A (cyclophilin A) has been
      shown to have multiple roles, including protein folding, regulation of protein
      kinases and phosphatases, immunoregulation, cell signaling, and redox status.
      Together, these results suggest that dietary VitD deficiency contributes to
      significant nitrosative stress in brain and may promote cognitive decline in
      middle-aged and elderly adults.

PMID- 23872024
TI  - Increased carbonylation of the lipid phosphatase PTEN contributes to Akt2
      activation in a murine model of early alcohol-induced steatosis.
AB  - The production of reactive aldehydes such as 4-hydroxynonenal (4-HNE) is a key
      event in the pathogenesis of alcoholic liver disease (ALD), which ranges from
      simple steatosis to fibrosis. The lipid phosphatase PTEN plays a central role in
      the regulation of lipid metabolism in the liver. In this study, the effects of
      chronic ethanol feeding and carbonylation on the PTEN signaling pathway were
      examined in a 9-week mouse feeding model for ALD. Chronic ethanol consumption
      resulted in altered redox homeostasis as evidenced by decreased GSH, decreased
      Trx1, and increased GST activity. Both PTEN expression and PTEN phosphorylation
      were significantly increased in the livers of ethanol-fed mice. Carbonylation of
      PTEN increased significantly in the ethanol-fed mice compared to pair-fed control
      animals, corresponding to decreased PTEN 3-phosphatase activity. Concomitantly,
      increased expression of Akt2 along with increased Akt phosphorylation at residues
      Thr(308), Thr(450), and Ser(473) was observed resulting in increased Akt2
      activity in the ethanol-fed animals. Akt2 activation corresponded to a decrease
      in cytosolic SREBP and ChREBP. Subsequent LC/MS/MS analysis of 4-HNE-modified
      recombinant human PTEN identified Michael addition adducts of 4-HNE on Cys(71),
      Cys(136), Lys(147), Lys(223), Cys(250), Lys(254), Lys(313), Lys(327), and
      Lys(344). Computational-based molecular modeling analysis of 4-HNE adducted to
      Cys(71) near the active site and Lys(327) in the C2 domain of PTEN suggested
      inhibition of enzyme catalysis via either stearic hindrance of the active-site
      pocket or prevention of C2 domain-dependent PTEN function. We hypothesize that 4
      HNE-mediated PTEN inhibition contributes to the observed activation of Akt2,
      suggesting a possible novel mechanism of lipid accumulation in response to
      increased reactive aldehyde production during chronic ethanol administration in
      mice. 

PMID- 23872026
TI  - Monitoring bacterially induced calcite precipitation in porous media using
      magnetic resonance imaging and flow measurements.
AB  - A range of nuclear magnetic resonance (NMR) techniques are employed to provide
      novel, non-invasive measurements of both the structure and transport properties
      of porous media following a biologically mediated calcite precipitation reaction.
      Both a model glass bead pack and a sandstone rock core were considered. Structure
      was probed using magnetic resonance imaging (MRI) via a combination of
      quantitative one-dimensional profiles and three-dimensional images, applied
      before and after the formation of calcite in order to characterise the spatial
      distribution of the precipitate. It was shown through modification and variations
      of the calcite precipitation treatment that differences in the calcite fill would
      occur but all methods were successful in partially blocking the different porous
      media. Precipitation was seen to occur predominantly at the inlet of the bead
      pack, whereas precipitation occurred almost uniformly along the sandstone core.
      Transport properties are quantified using pulse field gradient (PFG) NMR
      measurements which provide probability distributions of molecular displacement
      over a set observation time (propagators), supplementing conventional
      permeability measurements. Propagators quantify the local effect of calcite
      formation on system hydrodynamics and the extent of stagnant region formation.
      Collectively, the combination of NMR measurements utilised here provides a
      toolkit for determining the efficacy of a biological-precipitation reaction for
      partially blocking porous materials. 

PMID- 23872027
TI  - Experimental method for characterizing CVOC removal from fractured clays during
      boiling.
AB  - Conventional remediation methods that rely on contact with contaminants can be
      ineffective in fractured media, but thermal methods of remediation involving CVOC
      stripping at boiling temperature show promise. However, limited experimental data
      are available to characterize thermal remediation because of challenges
      associated with high temperature. This research reports an experimental method
      using uniformly contaminated clay packed into two types of experimental cells, a
      rigid-wall stainless steel tube and a flexible-wall Teflon tube in a pressurized
      chamber. Both tubes are 5 cm in diameter and approximately 25 cm long. This
      laboratory apparatus was developed as a 1D physical model for contaminant
      transport in a cylindrical matrix towards a fracture, which is represented by one
      end of the cylinder and serves as the outlet of vapor and contaminant. The clay
      was contaminated with dissolved 1,2-dichloroethane (DCA) and bromide, and the
      columns were heated to more than 100  degrees C and then the top end was
      depressurized to atmospheric pressure to induce boiling. The outflow was
      condensed and analyzed for contaminant mass. The flexible-wall cell was confined
      to 100 kPa (gage), allowing equilibrium boiling temperatures of approximately 120
      degrees C to be maintained. The clay was sampled before and after heating and
      extracted to determine the DCA distribution along the length of the column.
      During a typical test in the rigid-wall cell, internal temperatures and pressures
      along the column during heating reached the saturated vapor pressure curve. DCA
      concentrations in the recovered condensate were up to 12 times of the initial
      pore concentration in the clay. Less than 5% of non-volatile bromide was
      recovered. Significant removal of DCA and water occurred along the entire length
      of the clay column. This suggests that boiling was occurring in the clay matrix.

PMID- 23872028
TI  - Sacral neuromodulation in patients with idiopathic overactive bladder after
      initial botulinum toxin therapy.
AB  - PURPOSE: We evaluated whether patients with overactive bladder and incontinence
      who discontinued intravesical botulinum toxin therapy can be successfully treated
      with sacral neuromodulation. MATERIALS AND METHODS: All patients who were
      referred to our center after discontinuation of botulinum toxin-A between 2005
      and 2010 were included in this observational study. All patients underwent test
      stimulation with sacral neuromodulation and were evaluated with voiding diaries.
      Success was defined as more than 50% improvement in leakage episodes. Successful
      test stimulation was subsequently followed by a definitive implant. Patient
      satisfaction with sacral neuromodulation therapy was evaluated 1 year after the
      definitive implant. RESULTS: A total of 20 patients were included in the study.
      Of these patients 17 (85%) had discontinued botulinum toxin-A because of lack of
      efficacy and 3 had been treated successfully with botulinum toxin-A but requested
      a more permanent solution. The mean interval between the botulinum toxin-A and
      the sacral neuromodulation test stimulation was 23 months. In 14 patients (70%)
      the test stimulation was successful and they received a definitive implant. Of
      the 14 patients 5 even showed a decrease of greater than 90% in leakage episodes.
      One year after implantation 11 patients (79%) were satisfied with the sacral
      neuromodulation treatment. CONCLUSIONS: Despite the small sample size, this study
      indicates that patients who are dissatisfied with or in whom botulinum toxin-A
      treatment fails can respond successfully to sacral neuromodulation. The success
      rate of the test stimulation was comparable to that of patients who have never
      been treated with botulinum toxin-A. The 1-year satisfaction rate was comparable
      that of patients without a history of botulinum toxin-A treatment.

PMID- 23872025
TI  - MicroRNAs in skeletal muscle biology and exercise adaptation.
AB  - MicroRNAs (miRNAs) have emerged as important players in the regulation of gene
      expression, being involved in most biological processes examined to date. The
      proposal that miRNAs are primarily involved in the stress response of the cell
      makes miRNAs ideally suited to mediate the response of skeletal muscle to changes
      in contractile activity. Although the field is still in its infancy, the studies
      presented in this review highlight the promise that miRNAs will have an important
      role in mediating the response and adaptation of skeletal muscle to various modes
      of exercise. The roles of miRNAs in satellite cell biology, muscle regeneration,
      and various myopathies are also discussed. 

PMID- 23872029
TI  - Intravesical instillation of c-MYC inhibitor KSI-3716 suppresses orthotopic
      bladder tumor growth.
AB  - PURPOSE: c-MYC is a promising target for cancer therapy but its use is restricted
      by unwanted, devastating side effects. We explored whether intravesical
      instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in
      murine orthotopic bladder xenografts. MATERIALS AND METHODS: The small molecule
      KSI-3716, which blocks c-MYC/MAX binding to target gene promoters, was used as an
      intravesical chemotherapy agent. KSI-3716 action was assessed by electrophoretic
      mobility shift assay, chromatin immunoprecipitation, transcription reporter assay
      and quantitative reverse transcriptase-polymerase chain reaction. Inhibition of
      cell proliferation and its mechanism was monitored by cell cytotoxicity assay,
      EdU incorporation assay and flow cytometry. The in vivo efficacy of KSI-3716 was
      examined by noninvasive luminescence imaging and histological analysis after
      intravesical instillation of KSI-3716 in murine orthotopic bladder xenografts.
      RESULTS: KSI-3716 blocked c-MYC/MAX from forming a complex with target gene
      promoters. c-MYC mediated transcriptional activity was inhibited by KSI-3716 at
      concentrations as low as 1 MUM. The expression of c-MYC target genes, such as
      cyclin D2, CDK4 and hTERT, was markedly decreased. KSI-3716 exerted cytotoxic
      effects on bladder cancer cells by inducing cell cycle arrest and apoptosis.
      Intravesical instillation of KSI-3716 at a dose of 5 mg/kg significantly
      suppressed tumor growth with minimal systemic toxicity. CONCLUSIONS: The c-MYC
      inhibitor KSI-3716 could be developed as an effective intravesical chemotherapy
      agent for bladder cancer.

PMID- 23872030
TI  - Consequences of interstitial cystitis/bladder pain symptoms on women's work
      participation and income: results from a national household sample.
AB  - PURPOSE: We describe differences in work participation and income by bladder
      symptom impact and comorbidities among women with interstitial cystitis/bladder
      pain syndrome. MATERIALS AND METHODS: Cross-sectional data from 2,767 respondents
      younger than 65 years identified with interstitial cystitis/bladder pain syndrome
      symptoms were analyzed. The data were taken from the RAND Interstitial Cystitis
      Epidemiology (RICE) survey, and included retrospective self-reports of
      interstitial cystitis/bladder pain syndrome impact, severity, years since onset,
      related comorbidities (depressive symptomatology, number of conditions), work
      participation and income, and personal characteristics. Multiple regressions
      predicted 5 current work outcomes of works now, kept from working by pain, missed
      work days, days worked when bothered by symptoms and real income change since
      symptom onset. RESULTS: Controlling for work status at symptom onset and personal
      characteristics, greater bladder symptom impact predicted a greater likelihood of
      not now working, kept more days from working by pain, missed more work days and
      working more days with symptoms. More depressive symptomatology and greater
      number of comorbidities predicted reduced work participation. Women experienced
      no growth in real income since symptom onset. Measures of symptom severity were
      not associated with any of the economic outcomes. CONCLUSIONS: Greater
      interstitial cystitis/bladder pain syndrome symptom impact, depressive
      symptomatology and count of comorbidities (but not symptom severity) were each
      associated with less work participation and leveling of women's long-term
      earnings. Management of bladder symptom impact on nonwork related activities and
      depressive symptomatology may improve women's work outcomes.

PMID- 23872031
TI  - Pancreaticojejunostomy by reinforcing the pancreas without covering the
      anastomotic line reduces pancreatic fistula.
AB  - BACKGROUND/OBJECTIVE: Postoperative pancreatic fistula (POPF) is the most common
      and an intractable complication after pancreaticoduodenectomy (PD). Many efforts
      have been made to lessen POPF, but nevertheless its incidence still remains high.
      The aim of this study was to evaluate the efficacy of reinforcing the pancreatic
      remnant, but the non-reinforcement of the anastomotic line, by using a modified
      polyethylene glycolic acid (PGA) felt pasting method after PD, especially in
      cases with a soft pancreas. METHODS: Pancreaticojejunostomy (PJ) anastomosis was
      performed with the end-to-side 2-layer manner in which the cut end of the
      pancreatic remnant was pasted with PGA felts using a fibrin sealant in 31
      patients (PGA group). The postoperative outcome was then compared with historical
      control subjects (control group, 33 patients). RESULTS: Incidences of overall,
      Grade A and Grade B of POPF in the PGA group were 29.0, 22.6 and 6.5%,
      respectively, and tended to be lower than that in the control group (48.5, 33.3
      and 15.2%), although no statistical significance was observed. There was no Grade
      C of POPF in this study. Referring only to the soft pancreas, however, the
      overall incidence of POPF in the PGA group was significantly lower than that in
      the control group (39.1 vs. 70.0%, p = 0.042). CONCLUSION: Applying PGA felt
      pasting to PJ anastomosis could be one effective measure for reducing POPF after
      PD.

PMID- 23872032
TI  - Systematic review of sentinel lymph node biopsy in anal squamous cell carcinoma.
AB  - BACKGROUND: Anal squamous cell carcinoma with lymph node metastases carries a
      poor outcome. There remains a need for a better method to diagnose inguinal lymph
      node metastases which is minimally invasive, accurate and avoids unnecessary
      irradiation to the groin with its associated significant co-morbidity. The aim of
      this study was to evaluate the role of sentinel lymph node (SLN) biopsy in anal
      squamous cell carcinoma. METHODS: The systematic review was conducted in
      accordance with PRISMA guidelines. The Medline, Central and Embase databases were
      searched using the terms 'sentinel lymph node' and 'anus neoplasms'. RESULTS: The
      systematic review identified 17 studies, containing 270 patients. SLN detection
      rate varied from 47% to 100%. The presence of nodal metastases varied from 0 to
      44%. The complication rate varied from 0 to 59%. The rate of development of
      subsequent inguinal lymph node metastases in those previously SLN biopsy-negative
      (a surrogate marker for false negative rate) ranged from 0 to 18.75%. CONCLUSION:
      SLN biopsy is a feasible method of assessing lymph node status in patients with
      anal squamous cell carcinoma. Longer follow up is required to evaluate the
      proportion of patients who are SLN biopsy-negative and subsequently develop nodal
      metastases. More studies are required to ascertain whether SLN biopsy should be
      the main method of assessing inguinal lymph node involvement in patients with
      anal squamous cell carcinoma.

PMID- 23872033
TI  - Hip fracture surgery: does time of the day matter? A case-controlled study.
AB  - INTRODUCTION: A prevailing perception regarding night time surgery is that the
      probability of complications may be higher due to decreased availability of
      support staff, surgeon fatigue and other logistical factors. However there is
      little data supporting this notion in hip fracture surgery and we studied this in
      the context of Inter-trochanteric fractures fixed with dynamic hip screws (DHS).
      METHODS: All patients who underwent DHS fixation for inter-trochanteric fracture
      from January 2005 to December 2010 were included. Patients were divided into two
      groups. An after-hours group was defined as an operation done between 5:00 P.M.
      to 7:00 A.M. and a daytime group was defined as surgery done between 7:00 A.M. to
      5:00 P.M. Data was analyzed using SPSS version 19. RESULTS: During this period
      194 patients underwent DHS fixation. One hundred and fourteen patients were
      included in the daytime group and 80 patients in the after-hours group. There was
      no difference in the rates of wound infection, length of hospital stay,
      postoperative ambulation status, intra op blood loss, type of anesthesia, and
      mortality between the two groups. Tip apex index was found to be similar between
      the two groups. Two patients in the daytime surgery required revision surgery
      compared to 5 patients in the after-hours group, however this difference was not
      statistically significant. DISCUSSION: Outcomes in terms of adequacy of fixation,
      post-operative complications and post-operative 30-day mortality are comparable
      to routine day time surgery while offering the benefits of early fixation and
      mobilization to the patient. This also has a positive impact on the financial
      burden on this population as early fixation translates into decreased length of
      stay and reduced cost of treatment.

PMID- 23872034
TI  - Amino acid sequence and biological characterization of BlatPLA2, a non-toxic
      acidic phospholipase A2 from the venom of the arboreal snake Bothriechis
      lateralis from Costa Rica.
AB  - Bothriechis is considered a monophyletic, basal genus of arboreal Neotropical
      pitvipers distributed across Middle America. The four species found in Costa Rica
      (B. lateralis, B. schlegeli, B. nigroviridis, B. supraciliaris) differ in their
      venom proteomic profiles, suggesting that different Bothriechis taxa have evolved
      diverse trophic strategies. In this study, we isolated a phospholipase A2 (PLA2)
      from B. lateralis venom, aiming at increasing our knowledge on the structural and
      functional characteristics of group II acidic PLA2s, whose toxic actions are
      generally more restricted than those displayed by basic PLA2s. The new acidic
      enzyme, BlatPLA2, occurs as a monomer of 13,917 Da, in contrast to many basic
      group II PLA2s which associate into dimers and often display myotoxicity and/or
      neurotoxicity. Its amino acid sequence of 122 residues predicts an isoelectric
      point of 4.7, and displays significant differences with previously characterized
      acidic PLA2s, with which it shows a maximum sequence identity of 78%. BlatPLA2 is
      catalytically active but appears to be devoid of major toxic activities, lacking
      intravenous or intracerebroventricular lethality, myotoxicity, in vitro
      anticoagulant activity, and platelet aggregation or inhibition effects.
      Phylogenetic relationships with similar group II enzymes suggest that BlatPLA2
      may represent a basal sequence to other acidic PLA2s. Due to the metabolic cost
      of venom protein synthesis, the presence of a relatively abundant (9%) but non
      toxic component is somewhat puzzling. Nevertheless, we hypothesize that BlatPLA2
      could have a role in the pre-digestion of prey, possibly having retained
      characteristics of ancestral PLA2s without evolving towards potent toxicity.

PMID- 23872035
TI  - An easily accessible Web-based minimization random allocation system for clinical
      trials.
AB  - BACKGROUND: Minimization as an adaptive allocation technique has been recommended
      in the literature for use in randomized clinical trials. However, it remains
      uncommonly used due in part to a lack of easily accessible implementation tools.
      OBJECTIVE: To provide clinical trialists with a robust, flexible, and readily
      accessible tool for implementing covariate-adaptive biased-coin randomization.
      METHODS: We developed a Web-based random allocation system, MinimRan, that
      applies Pocock-Simon (for trials with 2 or more arms) and 2-way (currently
      limited to 2-arm trials) minimization methods for trials using only categorical
      prognostic factors or the symmetric Kullback-Leibler divergence minimization
      method for trials (currently limited to 2-arm trials) using continuous prognostic
      factors with or without categorical factors, in covariate-adaptive biased-coin
      randomization. RESULTS: In this paper, we describe the system's essential
      statistical and computer programming features and provide as an example the
      randomization results generated by it in a recently completed trial. The system
      can be used in single- and double-blind trials as well as single-center and
      multicenter trials. CONCLUSIONS: We expect the system to facilitate the
      translation of the 3 validated random allocation methods into broad, efficient
      clinical research practice.

PMID- 23872036
TI  - Quantitative electron tomography: the effect of the three-dimensional point
      spread function.
AB  - The intensity levels in a three-dimensional (3D) reconstruction, obtained by
      electron tomography, can be influenced by several experimental imperfections.
      Such artifacts will hamper a quantitative interpretation of the results. In this
      paper, we will correct for artificial intensity variations by determining the 3D
      point spread function (PSF) of a tomographic reconstruction based on high angle
      annular dark field scanning transmission electron microscopy. The large tails of
      the PSF cause an underestimation of the intensity of smaller particles, which in
      turn hampers an accurate radius estimate. Here, the error introduced by the PSF
      is quantified and corrected a posteriori. 

PMID- 23872037
TI  - Minimizing electrostatic charging of an aperture used to produce in-focus phase
      contrast in the TEM.
AB  - Microfabricated devices designed to provide phase contrast in the transmission
      electron microscope must be free of phase distortions caused by unexpected
      electrostatic effects. We find that such phase distortions occur even when a
      device is heated to 300  degrees C during use in order to avoid the formation of
      polymerized, carbonaceous contamination. Remaining factors that could cause
      unwanted phase distortions include patchy variations in the work function of a
      clean metal surface, radiation-induced formation of a localized oxide layer, and
      creation of a contact potential between an irradiated area and the surround due
      to radiation-induced structural changes. We show that coating a microfabricated
      device with evaporated carbon apparently eliminates the problem of patchy
      variation in the work function. Furthermore, we show that a carbon-coated
      titanium device is superior to a carbon-coated gold device, with respect to
      radiation-induced electrostatic effects. A carbon-coated, hybrid double
      sideband/single-sideband aperture is used to record in-focus, cryo-EM images of
      monolayer crystals of streptavidin. Images showing no systematic phase error due
      to charging are achievable under conditions of low-dose data collection. The
      contrast in such in-focus images is sufficient that one can readily see
      individual streptavidin tetramer molecules. Nevertheless, these carbon-coated
      devices perform well for only a limited length of time, and the cause of failure
      is not yet understood.

PMID- 23872038
TI  - Bloch wave simulations in the frozen lattice approximation.
AB  - To simulate the effects of thermal diffuse scattering in the frozen lattice (FL)
      approximation, we modify the conventional Bloch wave method by applying the
      classical scattering matrix method. The present simulation method requires that
      the eigenvalue operation is executed only once for each partial incident wave
      using the atomic positions of the thermal equilibrium configuration and thus the
      calculation time decreases drastically. Furthermore, from a comparison of
      convergent beam electron diffraction (CBED) patterns simulated by the present
      method with the results of CBED patterns simulated by a multislice method, we
      confirm that FL approximation can be simulated by the dynamical simulation based
      on the Bloch wave method. 

PMID- 23872039
TI  - High-resolution noise substitution to measure overfitting and validate resolution
      in 3D structure determination by single particle electron cryomicroscopy.
AB  - Three-dimensional (3D) structure determination by single particle electron
      cryomicroscopy (cryoEM) involves the calculation of an initial 3D model, followed
      by extensive iterative improvement of the orientation determination of the
      individual particle images and the resulting 3D map. Because there is much more
      noise than signal at high resolution in the images, this creates the possibility
      of noise reinforcement in the 3D map, which can give a false impression of the
      resolution attained. The balance between signal and noise in the final map at its
      limiting resolution depends on the image processing procedure and is not easily
      predicted. There is a growing awareness in the cryoEM community of how to avoid
      such over-fitting and over-estimation of resolution. Equally, there has been a
      reluctance to use the two principal methods of avoidance because they give lower
      resolution estimates, which some people believe are too pessimistic. Here we
      describe a simple test that is compatible with any image processing protocol. The
      test allows measurement of the amount of signal and the amount of noise from
      overfitting that is present in the final 3D map. We have applied the method to
      two different sets of cryoEM images of the enzyme beta-galactosidase using
      several image processing packages. Our procedure involves substituting the
      Fourier components of the initial particle image stack beyond a chosen resolution
      by either the Fourier components from an adjacent area of background, or by
      simple randomisation of the phases of the particle structure factors. This
      substituted noise thus has the same spectral power distribution as the original
      data. Comparison of the Fourier Shell Correlation (FSC) plots from the 3D map
      obtained using the experimental data with that from the same data with high
      resolution noise (HR-noise) substituted allows an unambiguous measurement of the
      amount of overfitting and an accompanying resolution assessment. A simple formula
      can be used to calculate an unbiased FSC from the two curves, even when a
      substantial amount of overfitting is present. The approach is software
      independent. The user is therefore completely free to use any established method
      or novel combination of methods, provided the HR-noise test is carried out in
      parallel. Applying this procedure to cryoEM images of beta-galactosidase shows
      how overfitting varies greatly depending on the procedure, but in the best case
      shows no overfitting and a resolution of ~6 A. (382 words).

PMID- 23872040
TI  - Simulating realistic imaging conditions for in situ liquid microscopy.
AB  - In situ transmission electron microscopy enables the imaging of biological cells,
      macromolecular protein complexes, nanoparticles, and other systems in a near
      native environment. In order to improve interpretation of image contrast features
      and also predict ideal imaging conditions ahead of time, new virtual electron
      microscopic techniques are needed. A technique for virtual fluid-stage high-angle
      annular dark-field scanning transmission electron microscopy with the multislice
      method is presented that enables the virtual imaging of model fluid-stage systems
      composed of millions of atoms. The virtual technique is exemplified by simulating
      images of PbS nanoparticles under different imaging conditions and the results
      agree with previous experimental findings. General insight is obtained on the
      influence of the effects of fluid path length, membrane thickness, nanoparticle
      position, defocus and other microscope parameters on attainable image quality. 

PMID- 23872041
TI  - Backscattered electron imaging at low emerging angles: a physical approach to
      contrast in LVSEM.
AB  - Due to the influence of refraction effects on the escape probability of the Back
      Scattered Electrons (BSE), an expression of the fraction of these BSE is given as
      a function of the beam energy, E degrees , and emission angle (with respect to
      the normal) alpha. It has been shown that these effects are very sensitive to a
      local change of the work function in particular for low emerging angles. This
      sensitivity suggests a new type of contrast in Low Voltage Scanning Electron
      Microscopy (LVSEM for E degrees <2 keV): the work function contrast. Involving
      the change of phi with crystalline orientation, this possibility is supported by
      a new interpretation of a few published images. Some other correlated contrasts
      are also suggested. These are topographical contrasts or contrasts due to
      subsurface particles and cracks. Practical considerations of the detection system
      and its optimization are indicated.

PMID- 23872042
TI  - Optical image contrast enhancement in near-field optics induced by water
      condensation.
AB  - In surface science, water adsorption on hydrophilic samples is usually invoked,
      addressing their nanoscale experimental effects in scanning probe microscopy,
      especially when water condensates between tip and sample. Here we study by means
      of a numerical hybrid method the effect of water bridge formation in near field
      imaging. We show how this nanometric water neck plays an important role not only
      in the optical image, producing a high contrast at hydrophilic patches, but also
      in the tip-sample distance control. This work contributes with a new methodology
      able to retrieve the original application of SNOM, using it as an instrument to
      study the optical properties of matter overcoming the diffraction limit. It
      extends the application of SNOM to study the hydrophilic character of polymeric
      and biological samples, taking advantage of ubiquitous effect of humidity when
      operating in ambient condition. 

PMID- 23872043
TI  - A new correlation based alignment technique for use in electron tomography.
AB  - In this paper we present a new correlation based method for the alignment of a
      single axis tilt series. Rather than performing the pairwise correlation
      procedure with the central image as the starting point, the method presented here
      calculates the optimal starting position within the tilt series and proceeds
      towards both ends. The starting position is determined by maximisation of a
      viability function, J, which rewards cumulative series correlation and penalises
      both cumulative series shift and distance from the centre of the image series. 

PMID- 23872044
TI  - Omega-3 fatty acids can reverse the long-term deficits in hippocampal synaptic
      plasticity caused by prenatal ethanol exposure.
AB  - Fetal alcohol spectrum disorders result in long-lasting neurological deficits
      including decreases in synaptic plasticity and deficits in learning and memory.
      In this study we examined the effects of prenatal ethanol exposure on hippocampal
      synaptic plasticity in male and female Sprague-Dawley rats. Furthermore, we
      looked at the capacity for postnatal dietary intervention to rescue deficits in
      synaptic plasticity. Animals were fed an omega-3 enriched diet from birth until
      adulthood (PND55-70) and in vivo electrophysiology was performed by stimulating
      the medial perforant path input to the dentate gyrus and recording field
      excitatory post-synaptic potentials. LTP was induced by administering bursts of
      five 400 Hz pulses as a theta-patterned train of stimuli (200 ms inter-burst
      interval). Ethanol-exposed adult males, but not females, exhibited a significant
      reduction in LTP. This deficit in male animals was completely reversed with an
      omega-3 enriched diet. These results demonstrate that omega-3 fatty acids can
      have benefits following prenatal neuropathological insults and may be a viable
      option for alleviating some of the neurological deficits associated with FASD.

PMID- 23872045
TI  - Effect of long-term human exposure to environmental heavy metals on the
      expression of detoxification and DNA repair genes.
AB  - The present study was designed to evaluate the influence of long-term
      environmental human exposure to three heavy metals, lead (Pb), cadmium (Cd), and
      mercury (Hg), on the expression of detoxifying, xenobiotic metabolizing, and DNA
      repair genes in Mahd Ad-Dahab city. The study groups consisted of 40 healthy male
      residents (heavy metal-exposed) and 20 healthy male from Riyadh city, 700 km
      away, and served as control group. The heavy metal-exposed group with high
      exposure to Pb, Cd, or Hg was divided into three subgroups Pb-, Cd-, and Hg
      exposed groups, respectively. The mRNA expression levels of detoxifying, NQO1, HO
      1, GSTA1, MT-1, and HSP70, were significantly decreased in all heavy metal
      exposed group as compared to control group. This was accompanied with a
      proportional decrease in the expression of xenobiotic metabolizing gene,
      cytochrome P4501A1. On the other hand, the DNA repair gene OGG1 and the 8-OHdG
      level were dramatically inhibited in Cd-exposed group only.

PMID- 23872046
TI  - Photosynthetic performance of restored and natural mangroves under different
      environmental constraints.
AB  - We hypothesized that the photosynthetic performance of mangrove stands restored
      by the single planting of mangroves species would be lowered due to residual
      stressors. The photosynthetic parameters of the vegetation of three planted
      mangrove stands, each with a different disturbance history, were compared to
      reference sites and correlated with edaphic environmental variables. A
      permutational analysis of variance showed significant interaction when the
      factors were compared, indicating that the photosynthetic parameters of the
      restoration areas differed from the reference sites. A univariate analysis of
      variance showed that all the photosynthetic parameters differed between sites and
      treatments, except for photosynthetic efficiency (alphaETR). The combination of
      environmental variables that best explained the variations observed in the
      photosynthetic performance indicators were Cu, Pb and elevation disruptions.
      Fluorescence techniques proved efficient in revealing important physiological
      differences, representing a powerful tool for rapid analysis of the effectiveness
      of initiatives aimed at restoring coastal environments. 

PMID- 23872047
TI  - H-bond refinement for electron transfer membrane-bound protein-protein complexes:
      cytochrome c oxidase and cytochrome c552.
AB  - In this study we propose a protocol to evaluate membrane-bound cytochrome c
      oxidase-cytochrome c552 docking candidates. An initial rigid docking algorithm
      generates docking poses of the cytochrome c oxidase-cytochrome c552, candidates
      are then aggregated into a 512-DPPC membrane model and solvated in explicit
      solvent. Molecular dynamic simulations are performed to induce conformational
      changes to membrane-bound protein complexes. Lastly each protein-protein complex
      is optimized in terms of its hydrogen bond network, evaluated energetically and
      ranked. The protocol is directly applicable to other membrane-protein complexes,
      such as protein-ligand systems. 

PMID- 23872048
TI  - Effects of integrated motor imagery practice on gait of individuals with chronic
      stroke: a half-crossover randomized study.
AB  - OBJECTIVES: To test the effects of a new motor imagery practice approach, in
      which motor and motivational contents were integrated in order to improve gait in
      subjects with chronic poststroke hemiparesis. DESIGN: A half-crossover study
      composed of 2 phases. In phase 1, subjects were randomly assigned to receive
      either the experimental or the control treatment. In phase 2, the subjects who
      had initially received the control treatment "crossed over" to receive the
      experimental intervention. SETTING: The experimental and the control intervention
      were delivered in the subjects' homes; assessments were performed in a hospital
      laboratory. PARTICIPANTS: Community-dwelling individuals (N=23) with chronic
      poststroke hemiparesis whose gait was impaired. INTERVENTIONS: The experimental
      intervention, called integrated motor imagery practice, consisted of imagery
      scripts aimed at improving home and community walking as well as fall-related
      self-efficacy. The control treatment consisted of executed exercises to improve
      the function of the involved upper extremity. MAIN OUTCOME MEASURES: In-home
      walking, indoor and outdoor community ambulation, and fall-related self-efficacy.
      These were assessed before and after the intervention as well as at a 2-week
      follow-up. RESULTS: In-home walking was significantly improved after application
      of the experimental intervention (P<=.003), but not after the control treatment
      (P<=.68). Community ambulation did not improve. Fall-related self-efficacy was
      slightly improved by the integrated motor imagery intervention; however, the
      findings were not unequivocal. CONCLUSIONS: Home delivery of integrated motor
      imagery practice was feasible and exerted a positive effect on walking in the
      home. However, it was ineffective for improving gait in public domains. We
      speculate that the addition of physical practice to imagery practice may be
      essential for achieving that end.

PMID- 23872049
TI  - White matter lateralization and interhemispheric coherence to auditory
      modulations in normal reading and dyslexic adults.
AB  - Neural activation of slow acoustic variations that are important for syllable
      identification is more lateralized to the right hemisphere than activation of
      fast acoustic changes that are important for phoneme identification. It has been
      suggested that this complementary function at different hemispheres is rooted in
      a different degree of white matter myelination in the left versus right
      hemisphere. The present study will investigate this structure-function
      relationship with Diffusion Tensor Imaging (DTI) and Auditory Steady-State
      Responses (ASSR), respectively. With DTI we examined white matter lateralization
      in the cortical auditory and language regions (i.e. posterior region of the
      superior temporal gyrus and the arcuate fasciculus) and white matter integrity in
      the splenium of the corpus callosum. With ASSR we examined interhemispheric
      coherence to slow, syllabic-rate (i.e. 4 Hz) and fast, phonemic-rate (i.e. 20 Hz)
      modulations. These structural and functional techniques were applied in a group
      of normal reading adults and a group of dyslexic adults for whom previously
      reduced functional interhemispheric connectivity at 20 Hz has been reported
      (Poelmans et al. (2012). Ear and Hearing, 33, 134-143). This sample was chosen
      since it is hypothesized that in dyslexic readers insufficient hemispheric
      asymmetry in myelination might relate to their auditory and phonological
      problems. Results demonstrate reduced white matter lateralization in the
      posterior superior temporal gyrus and the arcuate fasciculus in the dyslexic
      readers. Additionally, white matter lateralization in the posterior superior
      temporal gyrus and white matter integrity in the splenium of the corpus callosum
      related to interhemispheric coherence to phonemic-rate modulations (i.e. 20 Hz).
      Interestingly, this correlation pattern was opposite in normal versus dyslexic
      readers. These results might imply that less pronounced left white matter
      dominance in dyslexic adults might relate to their problems to process phonemic
      rate acoustic information and to integrate them into the phonological system.

PMID- 23872050
TI  - Identification of the tetraspanin CD82 as a new barrier to xenotransplantation.
AB  - Significant immunological obstacles are to be negotiated before
      xenotransplantation becomes a clinical reality. An initial rejection of
      transplanted vascularized xenograft is attributed to Galalpha1,3Galbeta1,4GlcNAc
      R (Galalpha1,3-Gal)-dependent and -independent mechanisms. Hitherto, no receptor
      molecule has been identified that could account for Galalpha1,3-Gal-independent
      rejection. In this study, we identify the tetraspanin CD82 as a receptor molecule
      for the Galalpha1,3-Gal-independent mechanism. We demonstrate that, in contrast
      to human undifferentiated myeloid cell lines, differentiated cell lines are
      capable of recognizing xenogeneic porcine aortic endothelial cells in a calcium
      dependent manner. Transcriptome-wide analysis to identify the differentially
      expressed transcripts in these cells revealed that the most likely candidate of
      the Galalpha1,3-Gal-independent recognition moiety is the tetraspanin CD82. Abs
      to CD82 inhibited the calcium response and the subsequent activation invoked by
      xenogeneic encounter. Our data identify CD82 on innate immune cells as a major
      "xenogenicity sensor" and open new avenues of intervention to making
      xenotransplantation a clinical reality. 

PMID- 23872051
TI  - YB-1 is an early and central mediator of bacterial and sterile inflammation in
      vivo.
AB  - In vitro studies identified Y-box-binding protein (YB)-1 as a key regulator of
      inflammatory mediators. In this study, we observed increased levels of secreted
      YB-1 in sera from sepsis patients. This led us to investigate the in vivo role of
      YB-1 in murine models of acute peritonitis following LPS injection, in sterile
      renal inflammation following unilateral ureteral obstruction, and in experimental
      pyelonephritis. LPS injection enhanced de novo secretion of YB-1 into the urine
      and the peritoneal fluid of LPS-treated mice. Furthermore, we could demonstrate a
      significant, transient upregulation and posttranslational modification
      (phosphorylation at serine 102) of YB-1 in renal and inflammatory cells.
      Increased renal cytoplasmic YB-1 amounts conferred enhanced expression of
      proinflammatory chemokines CCL2 and CCL5. Along these lines, heterozygous YB-1
      knockout mice (YB-1(+/d)) that display 50% reduced YB-1 levels developed
      significantly lower responses to both LPS and sterile inflammation induced by
      unilateral ureteral obstruction. This included diminished immune cell numbers due
      to impaired migration propensities and reduced chemokine expression. YB-1(+/d)
      mice were protected from LPS-associated mortality (20% mortality on day 3 versus
      80% in wild-type controls); however, immunosuppression in YB-1(+/d) animals
      resulted in 50% mortality. In conclusion, our findings identify YB-1 as a major,
      nonredundant mediator in both systemic and local inflammatory responses. 

PMID- 23872053
TI  - Vinculin arrests motile B cells by stabilizing integrin clustering at the immune
      synapse.
AB  - Lymphocytes use integrin-based platforms to move and adhere firmly to the surface
      of other cells. The molecular mechanisms governing lymphocyte adhesion dynamics
      are however poorly understood. In this study, we show that in mouse B
      lymphocytes, the actin binding protein vinculin localizes to the ring-shaped
      integrin-rich domain of the immune synapse (IS); the assembly of this platform,
      triggered by cognate immune interactions, is needed for chemokine-mediated B cell
      motility arrest and leads to firm, long-lasting B cell adhesion to the APC.
      Vinculin is recruited early in IS formation, in parallel to a local
      phosphatidylinositol (4,5)-bisphosphate wave, and requires spleen tyrosine kinase
      activity. Lack of vinculin at the IS impairs firm adhesion, promoting, in turn,
      cell migration with Ag clustered at the uropod. Vinculin localization to the B
      cell contact area depends on actomyosin. These results identify vinculin as a
      major controller of integrin-mediated adhesion dynamics in B cells. 

PMID- 23872054
TI  - Tick-borne encephalitis (TBE) and hepatitis B nonresponders feature different
      immunologic mechanisms in response to TBE and influenza vaccination with
      involvement of regulatory T and B cells and IL-10.
AB  - Low responsiveness/nonresponsiveness is characterized by an insufficient immune
      response upon primary and/or booster vaccination and affects 1-10% of vaccinees.
      In the current study, we aimed to investigate whether nonresponsiveness is an
      Ag/vaccine-specific phenomenon and to clarify underlying immunological
      mechanisms. Nonresponders to tick-borne encephalitis (TBE) or hepatitis B Ag with
      a history of previous TBE vaccinations were booster vaccinated with TBE and
      influenza vaccine and compared with TBE high responders in terms of humoral and
      cellular immune response. Postboosters in TBE high responder existing TBE titers
      increased, and solid humoral responses to influenza vaccine were induced. In TBE
      nonresponders, low to undetectable prevaccination TBE titers remained low,
      whereas sufficient influenza Abs were induced. In both TBE groups, a positive
      correlation of humoral and cellular immune response was seen as high/low TBE
      titers were associated with sufficient/lack of Ag-specific T cell proliferation.
      Furthermore, responses to influenza were robust in terms of Abs and cytokine
      production. In contrast, in hepatitis B nonresponders, sufficient humoral
      responses to TBE and influenza Ags were induced despite lacking specific IL-2 and
      IFN-gamma production. Importantly, these patients showed high IL-10 baseline
      levels in vitro. HLA-DR subtypes associated with hepatitis B nonresponsiveness
      were overrepresented in this group, and high IL-10 levels were linked to these
      subtypes. Whereas TBE and hepatitis B nonresponders had increased IL-10-producing
      FOXP3(+) T regulatory cells upon vaccination, only in hepatitis B nonresponders,
      showing elevated prevaccination IL-10 levels, a prominent population of B
      regulatory cells was detected. We conclude that immunological pathways of
      nonresponsiveness follow different patterns depending both on vaccine Ag and
      genetic predisposition of the vaccinee. 

PMID- 23872052
TI  - Plasma B lymphocyte stimulator and B cell differentiation in idiopathic pulmonary
      fibrosis patients.
AB  - We hypothesized B cells are involved in the pathogenesis of idiopathic pulmonary
      fibrosis (IPF), a progressive, restrictive lung disease that is refractory to
      glucocorticoids and other nonspecific therapies, and almost invariably lethal.
      Accordingly, we sought to identify clinically associated B cell-related
      abnormalities in these patients. Phenotypes of circulating B cells were
      characterized by flow cytometry. Intrapulmonary processes were evaluated by
      immunohistochemistry. Plasma B lymphocyte stimulating factor (BLyS) was assayed
      by ELISA. Circulating B cells of IPF subjects were more Ag differentiated, with
      greater plasmablast proportions (3.1 +/- 0.8%) than in normal controls (1.3 +/-
      0.3%) (p < 0.03), and the extent of this differentiation correlated with IPF
      patient lung volumes (r = 0.44, p < 0.03). CD20(+) B cell aggregates, diffuse
      parenchymal and perivascular immune complexes, and complement depositions were
      all prevalent in IPF lungs, but much less prominent or absent in normal lungs.
      Plasma concentrations of BLyS, an obligate factor for B cell survival and
      differentiation, were significantly greater (p < 0.0001) in 110 IPF (2.05 +/-
      0.05 ng/ml) than among 53 normal (1.40 +/- 0.04 ng/ml) and 90 chronic obstructive
      pulmonary disease subjects (1.59 +/- 0.05 ng/ml). BLyS levels were uniquely
      correlated among IPF patients with pulmonary artery pressures (r = 0.58, p <
      0.0001). The 25% of IPF subjects with the greatest BLyS values also had
      diminished 1-y survival (46 +/- 11%), compared with those with lesser BLyS
      concentrations (81 +/- 5%) (hazard ratio = 4.0, 95% confidence interval = 1.8
      8.7, p = 0.0002). Abnormalities of B cells and BLyS are common in IPF patients,
      and highly associated with disease manifestations and patient outcomes. These
      findings have implications regarding IPF pathogenesis and illuminate the
      potential for novel treatment regimens that specifically target B cells in
      patients with this lung disease. 

PMID- 23872055
TI  - Factors influencing the performance of G-quadruplex DNAzyme-based sensors.
AB  - G-quadruplex DNAzymes are peroxidase-like complexes formed by nucleic acid G
      quadruplexes and hemin. Compared with natural enzymes, G-quadruplex DNAzyme
      offers many advantages, thus making it a promising tool in the design of
      biosensors and chemical sensors. Many biosensors and chemical sensors based on G
      quadruplex DNAzymes have been reported. A number of factors may affect the
      performance of G-quadruplex DNAzyme-based sensors. Here we focus on some aspects
      to be taken into account when designing a G-quadruplex DNAzyme-based sensor.
      These include the G-quadruplex-forming G-rich sequence, solution components, the
      reaction substrate, and enrichment strategy for G-quadruplex DNAzyme. We also
      provide an outlook for further research on G-quadruplex DNAzyme-based sensors. 

PMID- 23872056
TI  - High resolution grating-assisted surface plasmon resonance fiber optic
      aptasensor.
AB  - A surface plasmon resonance biochemical sensor based on a tilted fiber Bragg
      grating imprinted in a single mode fiber core is demonstrated. A 30-50 nm thick
      gold coating on the cladding of the fiber provides the support for surface
      plasmon waves whose interaction with attached biomolecules is monitored at near
      infrared wavelengths near 1,550 nm. The transmission spectrum of the sensor
      provides a fine comb of narrowband resonances that overlap with the broader
      absorption of the surface plasmon and thus provide a unique tool to measure small
      shifts of the plasmon with high accuracy. The attachment on the gold surfaces of
      aptamers with specific affinities for proteins provides the required target
      analyte system and is shown to be functional in the framework of our sensing
      device. The implementation of the sensor either as a stand-alone device or as
      part of a multi-sensor platform is also described.

PMID- 23872057
TI  - Highly sensitive and flexible inkjet printed SERS sensors on paper.
AB  - Surface enhanced Raman spectroscopy (SERS) has the potential to be utilized for
      the detection of a broad range of chemicals in trace quantities. However, because
      of the cost and complexity of SERS devices, the technology has been unable to
      fill the needs of many practical applications, in particular the need for rapid,
      portable, on-site detection in the field. In this work, we review a new
      methodology for trace chemical detection using inkjet-printed SERS substrates on
      paper. The detection performance of the inkjet-printed SERS devices is
      demonstrated by detecting 1,2-Bis(4-pyridyl)ethylene (BPE) at a concentration as
      low as 1.8 ppb. We then illustrate the primary advantages of paper SERS
      substrates as compared to conventional SERS substrates. By leveraging lateral
      flow concentration, the detection limit of paper SERS substrates can be further
      improved. Two real-world applications are demonstrated. First, the inkjet-printed
      SERS substrates are used as "dipsticks" for detecting the fungicide malachite
      green in water. Then, the flexible paper-based SERS devices are used as swabs to
      collect and detect trace residues of the fungicide thiram from a surface. We
      predict that the combination of ultra-low-cost fabrication with the advantages of
      easy-to-use dipsticks and swabs and the option of lateral flow concentration
      position ink-jet printed SERS substrates as a technology which will enable the
      application of SERS in solving critical problems for chemical detection in the
      field.

PMID- 23872059
TI  - BRIC-seq: a genome-wide approach for determining RNA stability in mammalian
      cells.
AB  - We recently developed a novel transcriptome analysis method, termed 5'-bromo
      uridine (BrU) immunoprecipitation chase-deep sequencing analysis (BRIC-seq). BRIC
      seq enables the determination of genome-wide RNA stability by chasing
      chronological decreases of BrU-labeled RNAs under physiologically undisturbed
      conditions. The RNA half-life of each transcript is calculated from the
      decreasing number of BrU-labeled RNA sequence tags measured by deep sequencing of
      BrU-labeled RNAs. Here, we describe a detailed protocol and provide tips for BRIC
      seq, followed by computational analysis. 

PMID- 23872058
TI  - An engineered Fc variant of an IgG eliminates all immune effector functions via
      structural perturbations.
AB  - The Fc variant of IgG2, designated as IgG2sigma, was engineered with V234A/G237A
      /P238S/H268A/V309L/A330S/P331S substitutions to eliminate affinity for Fcgamma
      receptors and C1q complement protein and consequently, immune effector functions.
      IgG2sigma was compared to other previously well-characterized Fc 'muted'
      variants, including aglycosylated IgG1, IgG2m4 (H268Q/V309L/A330S/P331S, changes
      to IgG4), and IgG4 ProAlaAla (S228P/L234A/L235A) in its capacity to bind
      FcgammaRs and activate various immune-stimulatory responses. In contrast to the
      previously characterized muted Fc variants, which retain selective FcgammaR
      binding and effector functions, IgG2sigma shows no detectable binding to the
      Fcgamma receptors in affinity and avidity measurements, nor any detectable
      antibody-dependent cytotoxicity, phagocytosis, complement activity, or Fc
      mediated cytokine release. Moreover, IgG2sigma shows minimal immunogenic
      potential by T-cell epitope analysis. The circulating half-life of IgG2sigma in
      monkeys is extended relative to IgG1 and IgG2, in spite of similar in vitro
      binding to recombinant FcRn. The three-dimensional structure of the Fc, needed
      for assessing the basis for the absence of effector function, was compared with
      that of IgG2 revealing a number of conformational differences near the hinge
      region of the CH2 domain that result from the amino acid substitutions. Modeling
      reveals that at least one of the key interactions with FcgammaRs is disrupted by
      a conformational change that reorients P329 to a position that prevents it from
      interacting with conserved W90 and W113 residues of the FcgammaRs. Inspection of
      the structure also indicated significant changes to the conformations of D270 and
      P329 in the CH2 domain that could negatively impact C1q binding. Thus, structural
      perturbations of the Fc provide a rationale for the loss of function. In toto,
      these properties of IgG2sigma suggest that it is a superior alternative to
      previously described IgG variants of minimal effector function, for future
      therapeutic applications of non-immunostimulatory mAb and Fc-fusion platforms.

PMID- 23872060
TI  - Carbon nanotube-based aptasensors for the rapid and ultrasensitive detection of
      bacteria.
AB  - In this paper we present a new generation of potentiometric biosensors based on
      carbon nanotubes (transducer layer of the biosensor) and aptamers (sensing layer
      of the biosensor) for the ultralow and selective detection of microorganisms. We
      show that with these aptasensors we were able to detect a few CFU of the target
      bacteria almost in real-time, both in buffered and in real samples. 

PMID- 23872061
TI  - A simple, robust and highly efficient transient expression system for producing
      antibodies.
AB  - Transient expression systems in mammalian cells have become the method of choice
      for producing research quantities of antibodies. Both the speed and yield of the
      available transient systems and the natural posttranslational modifications favor
      these systems above expression in lower eukaryotes, prokaryotes or stable cell
      lines. We describe an optimized mammalian transient expression system, capable of
      producing up to 400mg/L of native secreted antibodies in less than a week. The
      system is composed of commercially available components and is based on
      expression in the fast growing suspension cell line, FreeStyleTM 293-F (HEK
      293F). The method depends on an optimal combination of a gene transfer method, an
      expression vector and cotransfection with expression enhancing plasmids, encoding
      the large T antigen of the SV40 virus and the cell cycle inhibitors p21 and p27.
      Optimization of all components of the expression system, by experimental design
      techniques, yielded maximal expression levels (including antibody isotypes IgG1,
      2, 3, 4 and Fab fragments of various species). Expression volumes were scalable
      from 0.1 ml up to 1.2L in a simple shaker flask system in animal component free,
      low protein medium, enabling consistent production of relatively high amounts of
      a large number of native antibodies.

PMID- 23872062
TI  - Cyclic enzymatic amplification method (CEAM) based on exonuclease III for highly
      sensitive bioanalysis.
AB  - Nucleic acid molecular probes (NAMPs) have been widely used in the sensing of
      various chemical and biological substances, as well as physical parameters.
      However, for traditional nucleic acid molecular probes, the stoichiometric 1:1
      binding ratio limits the signal enhancement and thus the sensitivity of the
      assay. In order to overcome this problem, the cyclic enzymatic amplification
      method (CEAM) based on exonuclease III has been applied in optical and electrical
      detection of DNA, proteins and small molecules with excellent sensitivity,
      selectivity, versatility and simplicity. In this review, the working principle of
      CEAM is first introduced, followed by the applications of CEAM using different
      output signals for various analytes. Finally, experimental designs and procedures
      of CEAM are discussed in detail using displacing probes-based CEAM and linear
      molecular beacons (LMBs)-based CEAM as two examples.

PMID- 23872063
TI  - Dual effect of chemokine CCL7/MCP-3 in the development of renal
      tubulointerstitial fibrosis.
AB  - Most end-stage renal disease kidneys display accumulation of extracellular matrix
      (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF)
      which is strongly correlated with the future loss of renal function. Although
      inflammation is a key event in the development of TIF, it can also have a
      beneficial anti-fibrotic role depending in particular on the stage of the
      pathology. Chemokines play an important role in monocyte extravasation in the
      inflammatory process. CCL2 has already been shown to be involved in the
      development of TIF but CCL7, a close relative of CCL2 and able to bind to similar
      receptors, has not been studied in renal disease. We therefore studied chemokine
      CCL7 in a model of unilateral ureteral obstruction (UUO)-induced TIF. We observed
      that the role of CCL7 differs depending on the stage of the pathology. In early
      stages (0-8 days), CCL7 deficient (CCL7-KO) mice displayed attenuated TIF
      potentially involving two mechanisms: an early (0-3 days) decrease of
      inflammatory cell infiltration followed (3-8 days) by a decrease in tubular ECM
      production independent of inflammation. In contrast, during later stages of
      obstruction (10-14 days), CCL7-KO mice displayed increased TIF which was again
      associated with reduced inflammation. Interestingly, the switch between this anti
      to profibrotic effect was accompanied by an increased influx of
      immunosuppressive regulatory T cells. In conclusion, these results highlight for
      the first time a dual role for CCL7 in the development of renal TIF, deleterious
      in early stages but beneficial during later stages.

PMID- 23872064
TI  - miR-21 coordinates tumor growth and modulates KRIT1 levels.
AB  - miR-21 is overexpressed in tumors and it displays oncogenic activity. Here, we
      show that expression of miR-21 in primary tumors anticorrelates with KRIT1/CCM1,
      an interacting partner of the Ras-like GTPase Rap1, involved in Cerebral
      Cavernous Malformations (CCM). We present evidences that miR-21 silences KRIT1 by
      targeting its mRNA 3'UTR and that this interaction is involved in tumor growth
      control. In fact, miR-21 over-expression or KRIT1 knock-down promote anchorage
      independent tumor cell growth compared to controls, whereas the opposite is
      observed when anti-miR-21 or KRIT1 overexpression are employed. Our findings
      suggest that miR-21 promotes tumor cell growth, at least in part, by down
      modulating the potential tumor suppressor KRIT1. 

PMID- 23872065
TI  - miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn's
      disease.
AB  - Crohn's disease (CD) is one of the two major types of inflammatory bowel disease
      (IBD) thought to be caused by genetic and environmental factors. Recently, miR
      122 was found to be deregulated in association with CD progression. However, the
      underlying molecular mechanisms remain unclear. In the present study, the gene
      nucleotide-binding oligomerization domain 2 (NOD2/CARD15), which is strongly
      associated with susceptibility to CD, was identified as a functional target of
      miR-122. MiR-122 inhibited LPS-induced apoptosis by suppressing NOD2 in HT-29
      cells. NOD2 interaction with LPS initiates signal transduction mechanisms
      resulting in the activation of nuclear factor kappaB (NF-kappaB) and the
      stimulation of downstream pro-inflammatory events. The activation of NF-kappaB
      was inhibited in LPS-stimulated HT-29 cells pretreated with miR-122 precursor or
      NOD2 shRNA. The expression of the pro-inflammatory cytokines TNF-alpha and IFN
      gamma was significantly decreased, whereas therelease of the anti-inflammatory
      cytokines IL-4 and IL-10 was increased in LPS-stimulated HT-29 cells pretreated
      with miR-122 precursor, NOD2 shRNA or the NF-kappaB inhibitor QNZ. Taken
      together, these results indicate that miR-122 and its target gene NOD2 may play
      an important role in the injury of intestinal epithelial cells induced by LPS. 

PMID- 23872066
TI  - Regulation of mating in the budding yeast Saccharomyces cerevisiae by the zinc
      cluster proteins Sut1 and Sut2.
AB  - The zinc cluster proteins Sut1 and Sut2 play a role in sterol uptake and
      filamentous growth in the budding yeast Saccharomyces cerevisiae. In this study,
      we show that they are also involved in mating. Cells that lack both SUT1 and SUT2
      were defective in mating. The expression of the genes NCE102 and PRR2 was
      increased in the sut1 sut2 double deletion mutant suggesting that Sut1 and Sut2
      both repress the expression of NCE102 and PRR2. Consistent with these data,
      overexpression of either SUT1 or SUT2 led to lower expression of NCE102 and PRR2.
      Furthermore, expression levels of NCE102, PRR2 and RHO5, another target gene of
      Sut1 and Sut2, decreased in response to pheromone. Prr2 has been identified as a
      mating inhibitor before. Here we show that overexpression of NCE102 and RHO5 also
      reduced mating. Our results suggest that Sut1 and Sut2 positively regulate mating
      by repressing the expression of the mating inhibitors NCE102, PRR2 and RHO5 in
      response to pheromone. 

PMID- 23872067
TI  - Oxidative damage associated with obesity is prevented by overexpression of CuZn-
      or Mn-superoxide dismutase.
AB  - The development of insulin resistance is the primary step in the etiology of type
      2 diabetes mellitus. There are several risk factors associated with insulin
      resistance, yet the basic biological mechanisms that promote its development are
      still unclear. There is growing literature that suggests mitochondrial
      dysfunction and/or oxidative stress play prominent roles in defects in glucose
      metabolism. Here, we tested whether increased expression of CuZn-superoxide
      dismutase (Sod1) or Mn-superoxide dismutase (Sod2) prevented obesity-induced
      changes in oxidative stress and metabolism. Both Sod1 and Sod2 overexpressing
      mice were protected from high fat diet-induced glucose intolerance. Lipid
      oxidation (F2-isoprostanes) was significantly increased in muscle and adipose
      with high fat feeding. Mice with increased expression of either Sod1 or Sod2
      showed a significant reduction in this oxidative damage. Surprisingly,
      mitochondria from the muscle of high fat diet-fed mice showed no significant
      alteration in function. Together, our data suggest that targeting reduced
      oxidative damage in general may be a more applicable therapeutic target to
      prevent insulin resistance than is improving mitochondrial function. 

PMID- 23872068
TI  - Gongylonema sp. infection in the scops owl (Otus scops).
AB  - Since 1997, it has been observed that fledging scops owls often develop necrotic
      plaques in their oral cavities, which in severe cases can even affect bone
      tissue. This condition has been defined as a necrotic oropharyngeal disease based
      on gross lesions. In 2011 alone, thirty-five cases were identified at the Brinzal
      Owl Rescue Centre (Madrid, Spain), of which four were chosen to perform a
      complete diagnostic study. Histopathology was carried out in three cases and
      cytology in one case. Using morphological traits cytology identified two larvae
      as third-stage larvae of a Spiruridae nematode. Histology detected parasite
      sections in the mucosal epithelium of the mouth of one owl. In addition, four
      samples of mucosal lesions were subjected to a PCR amplification of the nematode
      ribosomal RNA gene using a pair of universal primers, three of which were
      positive. Of available sequences, the sequence obtained showed the closest
      affinity to that of Gongylonema pulchrum (97.8-98.0%). Clinical treatment was
      based on supportive therapy, the daily removal of caseous material from the oral
      cavity and the administration of fenbendazol (50mg/kg PO for 5 days).
      Approximately 60% of the affected scops owls that arrived at the rescue centre in
      2011 were cured and released back into the wild. Clinical, pathological and
      molecular findings are consistent with Gongylonema sp. infection. Since no
      evidence of the presence of adult parasites was found, we suggest that these
      scops owls should be considered as accidental hosts. This is the first
      description of severe Gongylonema infection in fledgling scops owls, a disease
      can lead to starvation and death if proper treatment is not provided.

PMID- 23872070
TI  - IKK interacts with rictor and regulates mTORC2.
AB  - mTORC2, the mammalian target of rapamycin complex 2 is activated by upstream
      growth factors, and performs two major functions, phosphorylation of AKT at the
      serine of 473 and cell cycle-dependent organization of actin cytoskeleton.
      However, the mechanisms through which mTORC2 is triggered by these signals remain
      unclear. We demonstrated, for the first time, that inhibitor of nuclear factor
      kappa-B kinase (IKK) interacted with rictor and regulated mTORC2 activity. Not
      only endogenously, but ectopically expressed IKK alpha and IKK beta physically
      interacted with rictor. An in vitro binding assay revealed that rictor interacted
      with IKKalpha and IKKbeta from amino acids 999 to 1397. Moreover, chemical
      inhibition of IKK, knockdown of IKK by small interference RNA (siRNA), or ectopic
      expression of kinase-dead IKK (IKK KD) repressed phosphorylation of AKT (S473) in
      a variety of cell lines and decreased the kinase activity of mTORC2. In NIH 3T3
      cells, inhibition of IKK also reduced phosphorylation of protein kinase alpha
      (PKCalpha) (S657) and resulted in disorganization of actin cytoskeleton.
      Interestingly, the interaction between IKKalpha/beta and rictor was increased,
      while the mTOR-rictor association was attenuated by inhibition of IKK. We
      identified a novel signaling mechanism for the regulation of mTORC2 by IKK: IKK
      interacted with rictor and regulated the function of mTORC2 including
      phosphorylation of AKT (S473) and organization of actin cytoskeleton. Inactivated
      IKK interacted with rictor and competed against mTOR, which resulted in a reduced
      mTORC2 level and a decrease in mTORC2 activity.

PMID- 23872069
TI  - Lower dipeptidyl peptidase-4 following exercise training plus weight loss is
      related to increased insulin sensitivity in adults with metabolic syndrome.
AB  - Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin
      stimulated glucose uptake and is linked to obesity and metabolic syndrome.
      However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome
      is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role
      in explaining exercise-induced improvements in insulin sensitivity. Fourteen
      obese adults (67.9+/-1.2 years, BMI: 34.2+/-1.1kg/m(2)) with metabolic syndrome
      (ATP III criteria) underwent a 12-week supervised exercise intervention
      (60min/day for 5 days/week at ~85% HRmax). Plasma DPP-4 was analyzed using an
      enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the
      euglycemic-hyperinsulinemic clamp (40mU/m(2)/min) and estimated by HOMA-IR.
      Visceral fat (computerized tomography), 2-h glucose levels (75g oral glucose
      tolerance), and basal fat oxidation as well as aerobic fitness (indirect
      calorimetry) were also determined before and after exercise. The intervention
      reduced visceral fat, lowered blood pressure, glucose and lipids, and increased
      aerobic fitness (P<0.05). Exercise improved clamp-derived insulin sensitivity by
      75% (P<0.001) and decreased HOMA-IR by 15% (P<0.05). Training decreased plasma
      DPP-4 by 10% (421.8+/-30.1 vs. 378.3+/-32.5ng/ml; P<0.04), and the decrease in
      DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04),
      HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). Increased fat
      oxidation also correlated with lower 2-h glucose levels (r=-0.64; P<0.02).
      Exercise training reduces plasma DPP-4, which may be linked to elevated insulin
      sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a
      potential mechanism whereby exercise plus weight loss prevents/delays the onset
      of type 2 diabetes in adults with metabolic syndrome. 

PMID- 23872071
TI  - Interaction of PACAP with Sonic hedgehog reveals complex regulation of the
      hedgehog pathway by PKA.
AB  - Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar
      granule cell progenitors (cGCPs) and its aberrant activation causes a cerebellar
      cancer medulloblastoma. Pituitary adenylate cyclase activating polypeptide
      (PACAP) inhibits Shh-driven proliferation of cGCPs and acts as tumor suppressor
      in murine medulloblastoma. We show that PACAP blocks canonical Shh signaling by a
      mechanism that involves activation of protein kinase A (PKA) and inhibition of
      the translocation of the Shh-dependent transcription factor Gli2 into the primary
      cilium. PKA is shown to play an essential role in inhibiting gene transcription
      in the absence of Shh, but global PKA activity levels are found to be a poor
      predictor of the degree of Shh pathway activation. We propose that the core Shh
      pathway regulates a small compartmentalized pool of PKA in the vicinity of
      primary cilia. GPCRs that affect global PKA activity levels, such as the PACAP
      receptor, cooperate with the canonical Shh signal to regulate Gli protein
      phosphorylation by PKA. This interaction serves to fine-tune the transcriptional
      and physiological function of the Shh pathway. 

PMID- 23872072
TI  - Dysregulation of cystathionine gamma-lyase (CSE)/hydrogen sulfide pathway
      contributes to ox-LDL-induced inflammation in macrophage.
AB  - Hydrogen sulfide (H2S), mainly produced by cystathionine gamma-lyase (CSE) in
      vascular system, emerges as a novel gasotransmitter exerting anti-inflammatory
      and anti-atherosclerotic effects. Alterations of CSE/H2S pathway may thus be
      involved in atherosclerosis pathogenesis. However, the underlying mechanisms are
      poorly understood. The present study showed that the levels of CSE mRNA and
      protein expression, as well as H2S production were decreased in ox-LDL-treated
      macrophage. CSE overexpression reduced the ox-LDL-stimulated tumor necrosis
      factor-alpha (TNF-alpha) generation in Raw264.7 and primary macrophage while CSE
      knockdown enhanced it. Exogenous supplementation of H2S with NaHS and Na2S also
      decreased the production of TNF-alpha and intercellular adhesion molecule-1 (ICAM
      1) in ox-LDL-stimulated macrophage, and alleviated the adhesion of macrophage to
      endothelial monolayer. Cysteine, a CSE preferential substrate for H2S
      biosynthesis, produced similar effects on the pro-inflammatory cytokine
      generation, which were reversed by CSE inhibitors PAG and BCA, respectively.
      Moreover, NaHS and Na2S attenuated the phosphorylation and degradation of
      IkappaBalpha and p65 nuclear translocation, as well as JNK activation caused by
      ox-LDL. The JNK inhibitor suppressed the NF-kappaB transcription activity in ox
      LDL-treated cells. Furthermore, inhibitors of NF-kappaB (PDTC), ERK (U0126 and
      PD98059) and JNK (SP600125) partially blocked the suppression by ox-LDL on the
      CSE mRNA levels. Taken together, the findings demonstrate that ox-LDL may down
      regulate the CSE/H2S pathway, which plays an anti-inflammatory role in ox-LDL
      stimulated macrophage by suppressing JNK/NF-kappaB signaling. The study reveals
      new therapeutic strategies for atherosclerosis, based on modulating CSE/H2S
      pathway.

PMID- 23872073
TI  - Induction of renal fibrotic genes by TGF-beta1 requires EGFR activation, p53 and
      reactive oxygen species.
AB  - While transforming growth factor-beta (TGF-beta1)-induced SMAD2/3 signaling is a
      critical event in the progression of chronic kidney disease, the role of non-SMAD
      mechanisms in the orchestration of fibrotic gene changes remains largely
      unexplored. TGF-beta1/SMAD3 pathway activation in renal fibrosis (induced by
      ureteral ligation) correlated with epidermal growth factor receptor(Y845)
      (EGFR(Y845)) and p53(Ser15) phosphorylation and induction of disease causative
      target genes plasminogen activator inhibitor-1 (PAI-1) and connective tissue
      growth factor (CTGF) prompting an investigation of the mechanistic involvement of
      EGFR and tumor suppressor p53 in profibrotic signaling. TGF-beta1, PAI-1, CTGF,
      p53 and EGFR were co-expressed in the obstructed kidney localizing predominantly
      to the tubular and interstitial compartments. Indeed, TGF-beta1 activated EGFR
      and p53 as well as SMAD2/3. Genetic deficiency of either EGFR or p53 or
      functional blockade with AG1478 or Pifithrin-alpha, respectively, effectively
      inhibited PAI-1and CTGF induction and morphological transformation of renal
      fibroblasts as did SMAD3 knockdown or pretreatment with the SMAD3 inhibitor SIS3.
      Reactive oxygen species (ROS)-dependent mechanisms initiated by TGF-beta1 were
      critical for EGFR(Y845) and p53(Ser15) phosphorylation and target gene
      expression. The p22(Phox) subunit of NADPH oxidase was also elevated in the
      fibrotic kidney with an expression pattern similar to p53 and EGFR. EGF
      stimulation alone initiated, albeit delayed, c-terminal SMAD3 phosphorylation
      (that required the TGF-beta1 receptor) and rapid ERK2 activation both of which
      are necessary for PAI-1 and CTGF induction in renal fibroblasts. These data
      highlight the extensive cross-talk among SMAD2/3, EGFR and p53 pathways essential
      for expression of TGF-beta1-induced fibrotic target genes.

PMID- 23872074
TI  - Analysing the impact of nucleo-cytoplasmic shuttling of beta-catenin and its
      antagonists APC, Axin and GSK3 on Wnt/beta-catenin signalling.
AB  - The canonical Wnt signalling pathway plays a critical role in development and
      disease. The key player of the pathway is beta-catenin. Its activity is mainly
      regulated by the destruction complex consisting of APC, Axin and GSK3. In the
      nucleus, the complex formation of beta-catenin and TCF initiates target gene
      expression. Our study provides a comprehensive analysis of the role of nucleo
      cytoplasmic shuttling of APC, Axin, and GSK3 and the inactivation of beta-catenin
      by the destruction complex in Wnt/beta-catenin signalling. We address the
      following questions: Can nucleo-cytoplasmic shuttling of APC, Axin and GSK3
      increase the [beta-catenin/TCF] concentration? And, how is the [beta-catenin/TCF]
      concentration influenced by phosphorylation and subsequent degradation of nuclear
      beta-catenin? Based on experimental findings, we develop a compartmental model
      and conduct several simulation experiments. Our analysis reveals the following
      key findings: 1) nucleo-cytoplasmic shuttling of beta-catenin and its antagonists
      can yield a spatial separation between the said proteins, which results in a
      breakdown of beta-catenin degradation, followed by an accumulation of beta
      catenin and hence leads to an increase of the [beta-catenin/TCF] concentration.
      Our results strongly suggest that Wnt signalling can benefit from nucleo
      cytoplasmic shuttling of APC, Axin and GSK3, although they are in general beta
      catenin antagonising proteins. 2) The total robustness of the [beta-catenin/TCF]
      output is closely linked to its absolute concentration levels. We demonstrate
      that the compartmental separation of beta-catenin and the destruction complex
      does not only lead to a maximization, but additionally to an increased robustness
      of [beta-catenin/TCF] signalling against perturbations in the cellular
      environment. 3) A nuclear accumulation of the destruction complex renders the
      pathway robust against fluctuations in Wnt signalling and against changes in the
      compartmental distribution of beta-catenin. 4) Elucidating the impact of
      destruction complex inhibition, we show that the [beta-catenin/TCF] concentration
      is more effectively enhanced by inhibition of the kinase GSK3 rather than the
      binding of beta-catenin to the destruction complex.

PMID- 23872076
TI  - Mini-review: Brazilian fungi diversity for biomass degradation.
AB  - Brazil houses over 10% of the total number of known species on Earth, with a
      great diversity of plants and fungi. The collection, isolation, identification
      and conservation of filamentous fungi with relevance to agriculture,
      pharmaceutical, food and biotechnological industries in Biological Resource
      Centers (CRBs) is very important to the development of a nation's scientific and
      technological infrastructure. In Brazil, 36 fungal collections are registered in
      the database of International Collections. Several federal and state programs
      have encouraged the formation of a researcher's network in order to study natural
      resources and the nation's biodiversity. In this context, Brazilian researchers
      have been on the frontiers of knowledge, investigating the enzymatic systems from
      native filamentous fungi with potential for biomass degradation and
      biotechnological application. In this review, we address recent progress in
      Brazilian fungal research, focusing on the identification and study of fungi and
      enzymes with potential for biomass degradation and application in bioenergy. 

PMID- 23872077
TI  - Stepping in persons poststroke: comparison of voluntary and perturbation-induced
      responses.
AB  - OBJECTIVES: To examine the stepping performance during voluntary and waist-pull
      perturbation-induced step initiation in people with chronic stroke. DESIGN:
      Repeated-measures single-case design. SETTING: University-based research
      laboratory. PARTICIPANTS: Community-dwelling stroke survivors (N=10).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Ground reaction forces and
      kinematic data were recorded to assess anticipatory postural adjustments (APAs)
      and step characteristics for both voluntary and induced stepping conditions.
      RESULTS: Induced stepping was performed with both the paretic (35% trials) and
      nonparetic legs (65% trials). Induced first steps occurred earlier and were
      executed faster than rapid voluntary steps. Compared with voluntary stepping,
      induced first step APAs were shorter in duration. Step height was higher with the
      nonparetic leg for both stepping conditions. Use of the paretic leg increased
      (52%) during the diagonal perturbations that passively unloaded the stepping limb
      compared with the use of the paretic leg (33%) for forward perturbations.
      CONCLUSIONS: The results indicated differences in executing voluntary and induced
      stepping, and between the paretic and nonparetic limbs in individuals with
      chronic stroke. The findings suggested guidelines for using stepping as a
      component of neurorehabilitation programs for enhancing balance and mobility.
      Additional larger-scale studies remain to be undertaken to further investigate
      these issues.

PMID- 23872075
TI  - Constitutively active rhodopsin mutants causing night blindness are effectively
      phosphorylated by GRKs but differ in arrestin-1 binding.
AB  - The effects of activating mutations associated with night blindness on the
      stoichiometry of rhodopsin interactions with G protein-coupled receptor kinase 1
      (GRK1) and arrestin-1 have not been reported. Here we show that the monomeric
      form of WT rhodopsin and its constitutively active mutants M257Y, G90D, and T94I,
      reconstituted into HDL particles are effectively phosphorylated by GRK1, as well
      as two more ubiquitously expressed subtypes, GRK2 and GRK5. All versions of
      arrestin-1 tested (WT, pre-activated, and constitutively monomeric mutants) bind
      to monomeric rhodopsin and show the same selectivity for different functional
      forms of rhodopsin as in native disc membranes. Rhodopsin phosphorylation by GRK1
      and GRK2 promotes arrestin-1 binding to a comparable extent, whereas similar
      phosphorylation by GRK5 is less effective, suggesting that not all
      phosphorylation sites on rhodopsin are equivalent in promoting arrestin-1
      binding. The binding of WT arrestin-1 to phospho-opsin is comparable to the
      binding to its preferred target, P-Rh*, suggesting that in photoreceptors
      arrestin-1 only dissociates after opsin regeneration with 11-cis-retinal, which
      converts phospho-opsin into inactive phospho-rhodopsin that has lower affinity
      for arrestin-1. Reduced binding of arrestin-1 to the phospho-opsin form of G90D
      mutant likely contributes to night blindness caused by this mutation in humans.

PMID- 23872078
TI  - Depression treatment preferences after acute traumatic spinal cord injury.
AB  - OBJECTIVE: To examine preferences for depression treatment modalities and
      settings and predictors of treatment preference in persons with spinal cord
      injury (SCI). DESIGN: Cross-sectional surveys. SETTING: Rehabilitation inpatient
      services. PARTICIPANTS: Persons with traumatic SCI (N=183) undergoing inpatient
      rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patient
      Health Questionnaire-9 depression scale, history of psychiatric diagnoses and
      treatments, and a depression treatment preference survey. RESULTS: Among
      inpatients with SCI (28% had Patient Health Questionnaire-9 score >=10 indicating
      probable major depression), a physical exercise program was the most preferred
      treatment option (78% somewhat or very likely to try) followed by antidepressants
      prescribed by a primary care provider (63%) and individual counseling in a
      medical or rehabilitation clinic (62%). All modalities were preferred over group
      counseling. Although not statistically significant, more depressed individuals
      stated a willingness to try antidepressants and counseling than nondepressed
      individuals. Subjects preferred treatment in a medical/rehabilitation setting
      over a mental health setting. Those with a prior diagnosis of depression and a
      history of antidepressant use were significantly more willing to take an
      antidepressant. Age >=40 years was a significant predictor of willingness to
      receive individual counseling. CONCLUSIONS: Treatment preferences and patient
      education are important factors when choosing a depression treatment modality for
      patients with SCI. The results suggest that antidepressants, counseling, and
      exercise may be promising components of depression treatment in this population,
      particularly if they are integrated into medical or rehabilitation care.

PMID- 23872079
TI  - Long-term disability and survival in traumatic brain injury: results from the
      National Institute on Disability and Rehabilitation Research Model Systems.
AB  - OBJECTIVES: To document long-term survival in 1-year survivors of traumatic brain
      injury (TBI); to compare the use of the Disability Rating Scale (DRS) and FIM as
      factors in the estimation of survival probabilities; and to investigate the
      effect of time since injury and secular trends in mortality. DESIGN: Cohort study
      of 1-year survivors of TBI followed up to 20 years postinjury. Statistical
      methods include standardized mortality ratio, Kaplan-Meier survival curve,
      proportional hazards regression, and person-year logistic regression. SETTING:
      Postdischarge from rehabilitation units. PARTICIPANTS: Population-based sample of
      persons (N=7228) who were admitted to a TBI Model Systems facility and survived
      at least 1 year postinjury. These persons contributed 32,505 person-years, with
      537 deaths, over the 1989 to 2011 study period. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURE: Survival. RESULTS: Survival was poorer than that of the
      general population (standardized mortality ratio=2.1; 95% confidence interval,
      1.9-2.3). Age, sex, and functional disability were significant risk factors for
      mortality (P<.001). FIM- and DRS-based proportional hazards survival models had
      comparable predictive performance (C index: .80 vs .80; Akaike information
      criterion: 11,005 vs 11,015). Time since injury and current calendar year were
      not significant predictors of long-term survival (both P>.05). CONCLUSIONS: Long
      term survival prognosis in TBI depends on age, sex, and disability. FIM and DRS
      are useful prognostic measures with comparable statistical performance. Age- and
      disability-specific mortality rates in TBI have not declined over the last 20
      years. A survival prognosis calculator is available online
      (http://www.LifeExpectancy.org/tbims.shtml).

PMID- 23872080
TI  - Exercise for everyone: a randomized controlled trial of project workout on wheels
      in promoting exercise among wheelchair users.
AB  - OBJECTIVE: To compare the effectiveness of 2 home-based behavioral interventions
      for wheelchair users to promote exercise adoption and maintenance over 12 months.
      DESIGN: Randomized controlled trial, with participants stratified into groups
      based on disability type (stable, episodic, progressive) and support partner
      availability. SETTING: Exercise occurred in participant-preferred locations (eg,
      home, recreation center), with physiological data collected at a university-based
      exercise laboratory. PARTICIPANTS: Inactive wheelchair users (N=128; 64 women)
      with sufficient upper arm mobility for arm-based exercise were enrolled.
      Participants on average were 45 years of age and lived with their impairment for
      22 years, with spinal cord injury (46.1%) most commonly reported as causing
      mobility impairment. INTERVENTIONS: Both groups received home-based exercise
      interventions. The staff-supported group (n=69) received intensive exercise
      support, while the self-guided group (n=59) received minimal support. Both
      received exercise information, resistance bands, instructions to self-monitor
      exercise, regularly scheduled phone calls, and handwritten cards. MAIN OUTCOME
      MEASURES: The primary outcome derived from weekly self-reported exercise.
      Secondary outcomes included physical fitness (aerobic/muscular) and predictors of
      exercise participation. RESULTS: The staff-supported group reported significantly
      greater exercise (~17min/wk) than the self-guided group over the year (t=10.6,
      P=.00), with no significant between-group difference in aerobic capacity (t=.76,
      P=.45) and strength (t=1.5, P=.14). CONCLUSIONS: Although the staff-supported
      group reported only moderately more exercise, the difference is potentially
      clinically significant because they also exercised more frequently. The staff
      supported approach holds promise for encouraging exercise among wheelchair users,
      yet additional support may be necessary to achieve more exercise to meet national
      recommendations.

PMID- 23872081
TI  - Physical and psychosocial factors associated with physical activity in patients
      with chronic obstructive pulmonary disease.
AB  - OBJECTIVES: To assess physical activity and sitting time in patients with chronic
      obstructive pulmonary disease (COPD) and to investigate which physical and
      psychosocial factors are associated with physical activity and sitting time.
      DESIGN: Cross-sectional study. SETTING: Patients were recruited at outpatient
      clinics of general hospitals and from general practitioners. PARTICIPANTS:
      Patients (N=113) with mild to very severe COPD. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Physical activity and sitting time were measured with a
      triaxial accelerometer (24h/d). RESULTS: Mean locomotion time per 24 hours was
      6.8% (range, 0.7%-20.4%). Elevated physical activity was independently associated
      with higher self-efficacy, higher functional exercise capacity, and lower lung
      hyperinflation. Decreased physical activity was strongest in more severe stages
      of COPD, in which the patients were mainly limited by physical disease-specific
      factors (higher lung hyperinflation, worse dyspnea severity, worse leg muscle
      function, and oxygen use). In less severe patients, physical activity was
      independently associated with more generic factors (higher self-efficacy and the
      spring/summer season). Sitting time did not differ between severity stages, and
      longer sitting time in the total group was independently associated with more
      positive perception of treatment control, less autonomous motivation to exercise,
      not using sleep medication, and oxygen use. CONCLUSIONS: Both physical and
      psychosocial factors were associated with physical activity in patients with
      COPD. The factors associated with physical activity differed between disease
      severity stages, raising the question of whether physical activity enhancement
      programs should differ as well. Sitting time should be investigated further.

PMID- 23872082
TI  - Potential production of Hughlings Jackson's "parasitic consciousness" by
      physiologically-patterned weak transcerebral magnetic fields: QEEG and source
      localization.
AB  - Exotic experiences such as the sensing of another consciousness or the detachment
      of consciousness from the body are occasionally reported by individuals with
      partial seizures from a temporal lobe focus. The experiences display the
      characteristics of Hughlings Jackson's "parasitic consciousness". We have
      hypothesized that these experiences are encouraged by slight discrepancies in
      hemispheric activity that can be simulated by application of weak,
      physiologically-patterned magnetic fields across the cerebral hemispheres.
      Electroencephalographic and Low Resolution Electromagnetic Tomography (sLORETA)
      data revealed altered activity bands within specific regions within the cerebral
      cortices during these experiences. The clear changes in power of brain activity
      were discerned after consistent durations of exposure to specifically patterned
      weak magnetic fields. Millisecond range point durations were required. The
      technology may be useful to explore the subjective components associated with
      complex partial seizures. 

PMID- 23872083
TI  - Hypermotor seizures in lateral and mesial parietal epilepsy.
AB  - Four patients with refractory epilepsy and hypermotor seizures (HMS) benefited
      from an intracerebral investigation after a presurgical evaluation and
      demonstrated an ictal onset zone primarily involving the posterior cortex,
      specifically the posterior cingulate gyrus in two patients. At seizure onset,
      these two patients reported a falling sensation, followed by HMSs characterized
      by swinging movements of the trunk with intense grasping of the bed railing. The
      two other patients with lateral parietal seizure onset reported blurred vision
      and dizziness, followed by a mixed pattern of the previously described type 1 and
      2 HMSs. Three patients have been operated on, including two class I of Engel
      after 36 and 52months of follow-up. One patient developed a postoperative
      infection and continues to suffer seizures. Pathological findings disclosed a
      type IIa focal cortical dysplasia in all the patients. The last patient is
      awaiting surgery. Posterior cortex epilepsies, including those originating from
      the posterior cingulate cortex, can be responsible for HMSs. 

PMID- 23872084
TI  - Pharmacological and neuroethological studies of three antiepileptic drugs in the
      Genetic Audiogenic Seizure Hamster (GASH:Sal).
AB  - Epilepsy modeling is essential for understanding the basic mechanisms of the
      epileptic process. The Genetic Audiogenic Seizure Hamster (GASH:Sal) exhibits
      generalized tonic-clonic seizures of genetic origin in response to sound
      stimulation and is currently being validated as a reliable model of epilepsy.
      Here, we performed a pharmacological and neuroethological study using well-known
      and widely used antiepileptic drugs (AEDs), including phenobarbital (PB),
      valproic acid (VPA), and levetiracetam (LEV). The intraperitoneal administration
      of PB (5-20mg/kg) and VPA (100-300mg/kg) produced a dose-dependent decrease in
      GASH:Sal audiogenic seizure severity scores. The administration of LEV (30
      100mg/kg) did not produce a clear effect. Phenobarbital showed a short plasmatic
      life and had a high antiepileptic effect starting at 10mg/kg that was accompanied
      by ataxia. Valproic acid acted only at high concentrations and was the AED with
      the most ataxic effects. Levetiracetam at all doses also produced sedation and
      ataxia side effects. We conclude that the GASH:Sal is a reliable genetic model of
      epilepsy suitable to evaluate AEDs. 

PMID- 23872085
TI  - Systems biology: a biologist's viewpoint.
AB  - The debate over reductionism and antireductionism in biology is very old. Even
      the systems approach in biology is more than five decades old. However,
      mainstream biology, particularly experimental biology, has broadly sidestepped
      those debates and ideas. Post-genome data explosion and development of high
      throughput techniques led to resurfacing of those ideas and debates as a new
      incarnation called Systems Biology. Though experimental biologists have co-opted
      systems biology and hailed it as a paradigm shift, it is practiced in different
      shades and understood with divergent meanings. Biology has certain questions
      linked with organization of multiple components and processes. Often such
      questions involve multilevel systems. Here in this essay we argue that systems
      theory provides required framework and abstractions to explore those questions.
      We argue that systems biology should follow the logical and mathematical approach
      of systems theory and transmogrification of systems biology to mere collection of
      higher dimensional data must be avoided. Therefore, the questions that we ask and
      the priority of those questions should also change. Systems biology should focus
      on system-level properties and investigate complexity without shying away from
      it. 

PMID- 23872086
TI  - High molecular weight components of the injected venom of fish-hunting cone
      snails target the vascular system.
AB  - The venom of marine cone snails is a rich source of pharmacotherapeutic compounds
      with striking target specificity and functional diversity. Small, disulfide-rich
      peptide toxins are the most well characterized active compounds in cone snail
      venom. However, reports on the presence of larger polypeptides have recently
      emerged. The majority of these studies have focused on the content of the
      dissected venom gland rather than the injected venom itself. Recent breakthroughs
      in the sensitivity of protein and nucleotide sequencing techniques allow for the
      exploration of the proteomic diversity of injected venom. Using mass
      spectrometric analysis of injected venoms of the two fish-hunting cone snails
      Conus purpurascens and Conus ermineus, we demonstrate the presence of angiotensin
      converting enzyme-1 (ACE-1) and endothelin converting enzyme-1 (ECE-1),
      metalloproteases that activate potent vasoconstrictive peptides. ACE activity was
      confirmed in the venom of C. purpurascens and was significantly reduced in venom
      preincubated with the ACE inhibitor captopril. Reverse-transcription PCR
      demonstrated that these enzymes are expressed in the venom glands of other cone
      snail species with different prey preferences. These findings strongly suggest
      that cone snails employ compounds that cause disruption of cardiovascular
      function as part of their complex envenomation strategy, leading to the
      enhancement of neurotropic peptide toxin activity. BIOLOGICAL SIGNIFICANCE: To
      our knowledge, this is the first study to show the presence of ACE and ECE in the
      venom of cone snails. Identification of these vasoactive peptide-releasing
      proteases in the injected venoms of two fish-hunting cone snails highlights their
      role in envenomation and enhances our understanding of the complex hunting
      strategies utilized by these marine predators. Our findings on the expression of
      these enzymes in other cone snail species suggests an important biological role
      of ACE and ECE in these animals and points towards recruitment into venom from
      general physiological processes.

PMID- 23872087
TI  - Age-related changes in the mitochondrial proteome of the fungus Podospora
      anserina analyzed by 2D-DIGE and LC-MS/MS.
AB  - Many questions concerning the molecular processes during biological aging remain
      unanswered. Since mitochondria are central players in aging, we applied
      quantitative two-dimensional difference gel electrophoresis (2D-DIGE) coupled to
      protein identification by mass spectrometry to study the age-dependent changes in
      the mitochondrial proteome of the fungus Podospora anserina - a well-established
      aging model. 67 gel spots exhibited significant, but remarkably moderate
      intensity changes. While typically the observed changes in protein abundance
      occurred progressively with age, for several proteins a pronounced change was
      observed at late age, sometimes inverting the trend observed at younger age. The
      identified proteins were assigned to a wide range of metabolic pathways including
      several implicated previously in biological aging. An overall decrease for
      subunits of complexes I and V of oxidative phosphorylation was confirmed by
      Western blot analysis and blue-native electrophoresis. Changes in several groups
      of proteins suggested a general increase in protein biosynthesis possibly
      reflecting a compensatory mechanism for increased quality control-related protein
      degradation at later age. Age-related augmentation in abundance of proteins
      involved in biosynthesis, folding, and protein degradation pathways sustain these
      observations. Furthermore, a significant decrease of two enzymes involved in the
      degradation of gamma-aminobutyrate (GABA) supported its previously suggested
      involvement in biological aging. BIOLOGICAL SIGNIFICANCE: We have followed the
      time course of changes in protein abundance during aging of the fungus P.
      anserina. The observed moderate but significant changes provide insight into the
      molecular adaptations to biological aging and highlight the metabolic pathways
      involved, thereby offering new leads for future research.

PMID- 23872089
TI  - Paraventricular nucleus nesfatin-1 neurons are regulated by pituitary adenylate
      cyclase-activating polypeptide (PACAP).
AB  - Nesfatin-1 is a neuropeptide localized in hypothalamic paraventricular nucleus
      (PVN). Previously, we have reported the mechanism of feeding suppression by
      nesfatin-1, and also reported the ability of nesfatin-1 in regulating stress
      response and the circadian feeding pattern. Pituitary adenylate cyclase
      activating polypeptide (PACAP) is a neuropeptide also related to the stress
      response, feeding, and regulation of cardiovascular and autonomic nervous
      systems. The neurons with receptors for PACAP are distributed in PVN. However,
      there are no reports showing the direct effect of PACAP on nesfatin-1 neurons. In
      order to explore the direct effect of PACAP on PVN nesfatin-1 neuron, we have
      measured the cytosolic free calcium ([Ca(2+)]i) using fura-2 microfluorometry in
      single neurons isolated from PVN of adult rats, followed by immunocytochemical
      identification of nesfatin-1 neurons. PACAP at 10(-15)M to 10(-9)M increased
      [Ca(2+)]i in dose dependent manner. PAC1 and VPAC2 receptor agonists also
      increased [Ca(2+)]i. Sixteen out of 40 neurons (40%) in PVN responded to 10(-9)M
      PACAP, and 12 out of 16 neurons (75%) which responded to 10(-9)M PACAP were found
      to be nesfatin-1 neurons. In this paper we show that PACAP directly activates
      nesfatin-1 neurons in PVN. The data suggest that nesfatin-1 controls feeding,
      stress response or autonomic response under PACAP regulation.

PMID- 23872088
TI  - Global proteomic analysis in trypanosomes reveals unique proteins and conserved
      cellular processes impacted by arginine methylation.
AB  - Arginine methylation is a common posttranslational modification with reported
      functions in transcription, RNA processing and translation, and DNA repair.
      Trypanosomes encode five protein arginine methyltransferases, suggesting that
      arginine methylation exerts widespread impacts on the biology of these organisms.
      Here, we performed a global proteomic analysis of Trypanosoma brucei to identify
      arginine methylated proteins and their sites of modification. Using an approach
      entailing two-dimensional chromatographic separation and alternating electron
      transfer dissociation and collision induced dissociation, we identified 1332
      methylarginines in 676 proteins. The resulting data set represents the largest
      compilation of arginine methylated proteins in any organism to date. Functional
      classification revealed numerous arginine methylated proteins involved in
      flagellar function, RNA metabolism, DNA replication and repair, and intracellular
      protein trafficking. Thus, arginine methylation has the potential to impact
      aspects of T. brucei gene expression, cell biology, and pathogenesis.
      Interestingly, pathways with known methylated proteins in higher eukaryotes were
      identified in this study, but often different components of the pathway were
      methylated in trypanosomes. Methylarginines were often identified in glycine rich
      contexts, although exceptions to this rule were detected. Collectively, these
      data inform on a multitude of aspects of trypanosome biology and serve as a guide
      for the identification of homologous arginine methylated proteins in higher
      eukaryotes. BIOLOGICAL SIGNIFICANCE: T. brucei is a protozoan parasite that
      causes lethal African sleeping sickness in humans and nagana in livestock,
      thereby imposing a significant medical and economic burden on sub-Saharan Africa.
      The parasite encounters very different environments as it cycles between
      mammalian and insect hosts, and must exert cellular responses to these varying
      milieus. One mechanism by which all cells respond to changing environments is
      through posttranslational modification of proteins. Arginine methylation is one
      such modification that can dramatically impact protein-protein and protein
      nucleic acid interactions and subcellular localization of proteins. To define the
      breadth of arginine methylation in trypanosomes and identify target proteins, we
      performed a global proteomic analysis of arginine methylated proteins in insect
      stage T. brucei. We identified 1332 methylarginines in 676 proteins, generating
      the largest compilation of methylarginine containing proteins in any organism to
      date. Numerous arginine methylated proteins function in RNA and DNA related
      processes, suggesting this modification can impact T. brucei genome integrity and
      gene regulation at numerous points. Other processes that appear to be strongly
      influenced by arginine methylation are intracellular protein trafficking,
      signaling, protein folding and degradation, and flagellar function. The
      widespread nature of arginine methylation in trypanosomes highlights its
      potential to greatly affect parasite biology and pathogenesis.

PMID- 23872090
TI  - Effects of muscle fatigue on grip and load force coordination and performance of
      manipulation tasks.
AB  - Muscle fatigue is known to be associated with a deteriorated muscle coordination
      and impaired movement performance in variety of voluntary movements. The aim of
      this study was to investigate the generally underexplored effect of muscle
      fatigue on both the coordination between grip force (GF; the force component
      perpendicular to the hand-object contact area that provides friction) and load
      force (LF; the parallel force component that can move the object or support the
      body) as well as movement performance in manipulation tasks. Fifteen participants
      performed a variety of static and dynamic manipulations both with and without a
      preceding procedure designed to fatigue the arm and hand muscles. The tasks
      involved exertion of ramp-and-hold and oscillation patterns of LF against an
      externally fixed instrumented device, and a simple lift of a freely moving
      device. The results revealed a fatigue-associated decrease in GF scaling (i.e.,
      the magnitude of GF relative to LF) and GF-LF coupling (correlation between GF
      and LF), while the task performance regarding the accuracy of exertion of the
      prescribed LF profiles remained unaffected. We conclude that muscle fatigue both
      partly decouples GF from LF and reduces the overall GF magnitude, which could
      potentially explain why hand-held objects are more likely to drop when
      manipulated with fatigued muscles. However, the unaffected task performance could
      be explained either by the relatively low level of muscle forces required by the
      tested tasks, the moderate level of the fatigue imposed, or both. 

PMID- 23872091
TI  - GABAergic responses of mammalian ependymal cells in the central canal neurogenic
      niche of the postnatal spinal cord.
AB  - The area surrounding the central canal of the postnatal mammalian spinal cord is
      a highly plastic region that exhibits many similarities to other postnatal
      neurogenic niches, such as the subventricular zone. Within this region, ependymal
      cells have been identified as neural stem cells however very little is known
      about their properties and how the local environment, including
      neurotransmitters, is capable of affecting them. The neurotransmitter GABA is
      present around the central canal and is known to affect cells within other
      postnatal neurogenic niches. This study used whole cell patch clamp
      electrophysiology and intracellular dye-loading in in vitro Wistar rat spinal
      cord slices to characterise ependymal cells and their ability to respond to GABA.
      Ependymal cells were defined by their passive response properties and low input
      resistances. Extensive dye-coupling was observed between ependymal cells; this
      was confirmed as gap junction coupling using the gap junction blocker, 18beta
      glycyrrhetinic acid, which significantly increased the input resistance of
      ependymal cells. GABA depolarised all ependymal cells tested; the partial
      antagonism of this response by bicuculline and gabazine indicates that GABA(A)
      receptors contribute to this response. A lack of effect by baclofen suggests that
      GABA(B) receptors do not contribute to the GABAergic response. The ability of
      ependymal cells to respond to GABA suggests that GABA could be capable of
      influencing the proliferation and differentiation of cells within the neurogenic
      niche of the postnatal spinal cord.

PMID- 23872092
TI  - Involvement of the dorsal hippocampal dopamine D2 receptors in histamine-induced
      anxiogenic-like effects in mice.
AB  - Anxiety-related behaviors increase histamine and dopamine release in the brain.
      On the other hand, central histamine counteracts reward and reinforcement
      processes mediated by the mesolimbic dopamine system. We investigated the effects
      of the histaminergic system and dopamine D2 receptors agents and their
      interactions on anxiety-related behaviors using the elevated plus-maze (EPM). The
      intra-hippocampal (Intra-CA1) microinjection of histamine (10 MUg/mouse)
      decreased the percentage of open arm time (%OAT) and open arm entries (%OAE) but
      not the locomotor activity, indicating an anxiogenic-like response. Quinpirole
      (0.5 and 2 MUg/mouse) or sulpiride (0.3 and 1 MUg/mouse) when injected into the
      dorsal hippocampus also induced anxiety-like behavior, however, the drugs
      reversed the anxiogenic response induced by the effective dose of histamine (10
      MUg/mouse). Taken together and under the present experimental design, our results
      indicate that activation of the dorsal hippocampal histaminergic receptors causes
      anxiety-like behaviors altered by dopamine D2 receptor agonist and antagonist.
      Histamine can decrease dopaminergic tone in the dorsal hippocampus through
      decreasing the endogenous dopamine release, whereas quinpirole does the same via
      the postsynaptic DA receptors' activation. Sulpiride however renders the same
      effect through autoreceptors' blockade and potentiated dopamine transmission.
      Thus, quinpirole and sulpiride seem to compensate the effects of the intra-CA1
      injection of exogenous histamine, and tend to exert anxiolytic effects in the
      presence of histamine.

PMID- 23872093
TI  - Possible effects of iron deposition on the measurement of DTI metrics in deep
      gray matter nuclei: an in vitro and in vivo study.
AB  - The aim of this study was to explore the possible effects of iron deposition on
      the measurement of diffusion tensor imaging (DTI) metrics in deep gray matter
      nuclei in the normal human brain. Susceptibility-weighted imaging (SWI) and DTI
      were performed on nine MnCl2 phantoms and 85 healthy adults. The SWI phase value
      (PV) and DTI metrics including fractional anisotropy (FA), mean diffusivity (MD),
      radial diffusivity (RD), and axial diffusivity (AD) were measured in phantoms and
      the frontal white matter (FWM), caudate (CA), putamen (PU), and globus pallidus
      (GP) of both hemispheres in healthy adults. The FA correlated linearly with PV
      and MnCl2 concentrations in phantoms. The PV in the PU was positively correlated
      with age. The FA was negatively correlated with age in the FWM and positively
      correlated with age in the PU. AD positively correlated with PV in CA, PU, and
      GP. FA increased with elevated PV in the PU when controlling for the impact of
      age. The age-related increasing of PV, which predominantly caused by iron
      deposition, probably influences the measurement of DTI metrics in the PU in the
      normal human brain and should be considered when diagnosing various
      neurodegenerative diseases using DTI metrics. 

PMID- 23872094
TI  - Beta-adrenoceptors in the hypothalamic paraventricular nucleus modulate the
      baroreflex in conscious rats.
AB  - The role of beta-adrenoceptors of the hypothalamic paraventricular nucleus (PVN)
      in modulation of the baroreflex was investigated in conscious rats. The
      baroreflex was induced by intravenous injection of phenylephrine, and then the
      extracellular concentration of norepinephrine in the PVN region determined using
      microdialysis and high-performance liquid chromatography. Next, the role of the
      beta-adrenoceptor in modulation of the baroreflex was investigated by perfusion
      of its antagonist or agonist into the PVN using microdialysis. Intravenous
      injection of phenylephrine increased the norepinephrine concentration in the PVN
      by 35.83 +/- 5.71%. Propranolol (an antagonist of the beta-adrenoceptor)
      significantly decreased the gain of reflex bradycardia, but did not affect the
      magnitude of blood-pressure increases in the baroreflex, resulting in reduced
      baroreflex sensitivity. Isoprenaline (an agonist of the beta-adrenoceptor)
      significantly increased the gain of reflex bradycardia without affecting blood
      pressure increases, leading to increased baroreflex sensitivity. Our results
      suggest that norepinephrine in the PVN facilitates the phenylephrine-induced
      baroreflex via beta-adrenoceptors.

PMID- 23872095
TI  - Progesterone, compared to medroxyprogesterone acetate, to C57BL/6, but not 5alpha
      reductase mutant, mice enhances object recognition and placement memory and is
      associated with higher BDNF levels in the hippocampus and cortex.
AB  - Progesterone (P4) may influence cognition in part through actions of its 5alpha
      reduced metabolite, allopregnanolone. Ovariectomized mice that were C57BL/6
      wildtype (WT), or deficient in the 5alpha-reductase Type 1 enzyme (5alpha
      reductase knockout; 5alphaRKO), were administered vehicle, P4, allopregnanolone,
      or medroxyprogesterone acetate (MPA) after training in the object recognition or
      placement tasks. WT mice administered P4 or allopregnanolone performed
      significantly better in the object recognition and placement tasks than did WT
      mice administered vehicle or MPA. 5alphaRKO mice administered allopregnanolone,
      but not P4, MPA, or vehicle showed enhanced performance in the object recognition
      and placement tasks. Levels of brain-derived neurotrophic factor (BDNF) in the
      prefrontal cortex and hippocampus were lowest among mice administered MPA. Thus,
      some of P4s effects to enhance cognitive performance may be incumbent upon its
      5alpha-reduction. 

PMID- 23872096
TI  - Cadmium-induced glutathionylation of actin occurs through a ROS-independent
      mechanism: implications for cytoskeletal integrity.
AB  - Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have
      previously shown that this involves a complex interplay involving activation of
      kinase signaling, protein translocation, and disruption of focal adhesions. Here
      we investigate the role that glutathionylation of actin plays in Cd(2+)
      associated cytoskeletal reorganization. Low concentrations of Cd(2+) (0.5-2 MUM)
      caused an increase in actin glutathionylation by 6h, whereas at higher
      concentrations glutathionylation remained at basal levels. Although oxidation
      with diamide increased glutathionylation, reactive oxygen species (ROS) were not
      involved in the Cd(2+)-dependent effect, as only Cd(2+) concentrations above 2
      MUM were sufficient to increase ROS. However, low [Cd(2+)] increased total
      glutathione levels without affecting the ratio of reduced/oxidized glutathione,
      and inhibition of glutathione synthesis suppressed actin glutathionylation.
      Cadmium increased the activity of the enzyme glutaredoxin, which influences the
      equilibrium between glutathionylated and deglutathionylated proteins and thus may
      influence levels of glutathionylated actin. Together these observations show that
      cadmium-dependent effects on actin glutathionylation are affected by glutathione
      metabolism and not by direct effects of ROS on thiol chemistry. In vitro
      polymerization assays with glutathionylated actin show a decreased rate of
      polymerization. In contrast, immunofluorescence of cytoskeletal structure in
      intact cells suggests that increases in actin glutathionylation accompanying
      increased glutathione levels occurring under low Cd(2+) exposure are protective
      in vivo, with cytoskeletal disruption ensuing only when higher Cd(2+)
      concentrations increase ROS levels and prevent an increase in actin-glutathione
      conjugates.

PMID- 23872097
TI  - Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3
      inhibitors induces bone formation and a unique bone turnover biomarker profile in
      rats.
AB  - Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone
      anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic
      and osteolytic metastatic bone disease. To understand the wnt pathway related to
      human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858,
      AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using
      human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone
      formation in vivo was investigated. Bone anabolism/resorption was determined
      using clinically relevant serum biomarkers as indicators of bone turnover and
      bone formation assessed in femurs by histopathology and pQCT/MUCT imaging. GSK-3
      inhibitors caused beta-catenin stabilisation in human and rat mesenchymal stem
      cells, stimulated hADSC commitment towards osteoblasts and osteogenic
      mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone
      turnover biomarkers and increased bone mass over 28 days exposure in rats. After
      7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation
      biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating
      increased bone anabolism and reduced resorption in rats. This biomarker profile
      was differentiated from anabolic agent PTH1-34 or the anti-resorptive Alendronate
      induced changes. Increased bone formation in cortical and cancellous bone as
      assessed by femur histopathology supported biomarker changes. 14 day AR79
      treatment increased bone mineral density and trabecular thickness, and decreased
      trabecular number and connectivity assessed by pQCT/MUCT. GSK-3 inhibition caused
      hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass
      associated with changes in bone turnover biomarkers confirmed in vivo bone
      formation and indicated uncoupling of bone formation and resorption.

PMID- 23872098
TI  - Regional cortical volume and cognitive functioning following traumatic brain
      injury.
AB  - There has been limited examination of the effect of brain pathology on subsequent
      function. The current study examined the relationships between regional variation
      in grey matter volume, age and cognitive impairment using a semi-automated image
      analysis tool. This study included 69 individuals with mild-to-severe TBI, 41 of
      whom also completed neuropsychological tests of attention, working memory,
      processing speed, memory and executive functions. A widespread reduction in grey
      matter volume was associated with increasing age. Regional volumes that were
      affected also related to the severity of injury, whereby the most severe TBI
      participants displayed the most significant pathology. Poorer retention of newly
      learned material was associated with reduced cortical volume in frontal,
      parietal, and occipital brain regions. In addition, poorer working memory and
      executive control performance was found for individuals with lower cortical
      volume in temporal, parietal, and occipital regions. These findings are largely
      in line with previous literature, which suggests that frontal, temporal, and
      parietal regions are integral for the encoding of memories into long-term
      storage, memory retrieval, and working memory. The present study suggests that
      automated image analysis methods may be used to explore the relationships between
      regional variation in grey matter volume and cognitive function following TBI. 

PMID- 23872099
TI  - Prospective and retrospective time perception are related to mental time travel:
      evidence from Alzheimer's disease.
AB  - Unlike prospective time perception paradigms, in which participants are aware
      that they have to estimate forthcoming time, little is known about retrospective
      time perception in normal aging and Alzheimer's disease (AD). Our paper addresses
      this shortcoming by comparing prospective and retrospective time estimation in
      younger adults, older adults, and AD patients. In four prospective tasks (lasting
      30s, 60s, 90s, or 120s) participants were asked to read a series of numbers and
      to provide a verbal estimation of the reading time. In four other retrospective
      tasks, they were not informed about time judgment until they were asked to
      provide a verbal estimation of four elapsed time intervals (lasting 30s, 60s,
      90s, or 120s). AD participants gave shorter verbal time estimations than older
      adults and younger participants did, suggesting that time is perceived to pass
      quickly in these patients. For all participants, the duration of the
      retrospective tasks was underestimated as compared to the prospective tasks and
      both estimations were shorter than the real time interval. Prospective time
      estimation was further correlated with mental time travel, as measured with the
      Remember/Know paradigm. Mental time travel was even higher correlated with
      retrospective time estimation. Our findings shed light on the relationship
      between time perception and the ability to mentally project oneself into time,
      two skills contributing to human memory functioning. Finally, time perception
      deficits, as observed in AD patients, can be interpreted in terms of dramatic
      changes occurring in frontal lobes and hippocampus. 

PMID- 23872100
TI  - Combined effects of aging and in vitro non-steroid anti-inflammatory drugs on
      kidney and liver mitochondrial physiology.
AB  - AIMS: Aging and drug-induced side effects may contribute to deteriorate
      mitochondrial bioenergetics in many tissues, including kidney and liver. One
      possibility is that the combination of both aging and drug toxicity accelerates
      the process of mitochondrial degradation, leading to progressive bioenergetic
      disruption. We therefore analyzed in vitro kidney (KM) and liver (LM)
      mitochondrial response to salicylate and diclofenac in old and adult animals.
      MAIN METHODS: Male-Wistar adult (19-wks) and aged (106-wks) rats were used. In
      vitro endpoints of oxygen consumption and membrane potential were evaluated in
      non-treated conditions (vehicle) and in the presence of salicylate (0.5mM) and
      diclofenac (50MUM). The susceptibility to calcium-induced permeability transition
      pore (MPTP) was assessed. Aconitase and C, -SH and MDA contents were measured.
      Apoptotic signaling was followed by measuring caspase 3, 8 and 9 activities, Bax,
      Bcl2 and CypD expression. ANT content was semi-quantified. KEY FINDINGS: In
      general, animal age alone compromised KM state 3 and LM ADP lag phase while
      resulting in decreased resistance to the MPTP. Aging decreased LM CypD and
      increased Mn-SOD. Kidney caspase 9-like activity was lower in aged group.
      Salicylate and diclofenac induced KM and LM dysfunction. ADP lag phase in KM was
      further increased in the aged group in the presence of diclofenac. No further
      impairments were observed regarding drug toxicity adding to the aging process.
      SIGNIFICANCE: Aging impaired KM and LM function despite no detected alterations
      on oxidative stress and apoptosis. However, aging did not further exacerbate KM
      and LM frailty induced by salicylate and diclofenac.

PMID- 23872101
TI  - Evaluation of the cardiolipin biosynthetic pathway and its interactions in the
      diabetic heart.
AB  - AIMS: We have previously reported alterations in cardiolipin content and inner
      mitochondrial membrane (IMM) proteomic make-up specifically in interfibrillar
      mitochondria (IFM) in the type 1 diabetic heart; however, the mechanism
      underlying this alteration is unknown. The goal of this study was to determine
      how the cardiolipin biosynthetic pathway and cardiolipin-IMM protein interactions
      are impacted by type 1 diabetes mellitus. MAIN METHODS: Male FVB mice were made
      diabetic by multiple low-dose streptozotocin injections and sacrificed five weeks
      post-diabetic onset. Messenger RNA was measured and cardiac mitochondrial
      subpopulations were isolated. Further mitochondrial functional experimentation
      included evaluating the protein expression of the enzymes directly responsible
      for cardiolipin biosynthesis, as well as ATP synthase activity. Interactions
      between cardiolipin and ATP synthase subunits were also examined. KEY FINDINGS:
      Western blot analysis revealed a significant decrease in cardiolipin synthase
      (CRLS) protein content in diabetic IFM, with a concomitant decrease in its
      activity. ATP synthase activity was also significantly decreased. We identified
      two novel direct interactions between two subunits of the ATP synthase F0 complex
      (ATP5F1 and ATP5H), both of which were significantly decreased in diabetic IFM.
      SIGNIFICANCE: Overall, these results indicate that type 1 diabetes mellitus
      negatively impacts the cardiolipin biosynthetic pathway specifically at CRLS,
      contributing to decreased cardiolipin content and loss of interactions with key
      ATP synthase F0 complex constituents in the IFM.

PMID- 23872102
TI  - Potential underuse of analgesics for recognized pain in nursing home residents
      with dementia: a cross-sectional study.
AB  - The expression of pain is altered in people with dementia (PWD), increasing the
      risk of undertreatment in that population. The objective of this study was to
      determine whether dementia and the absence of pain assessment in the patients'
      medical chart reduced the probability of analgesic use in a large sample of
      nursing home (NH) residents. This is a cross-sectional study using data from 6275
      residents (mean age 86 +/- 8.2 years; 73.7% women) from 175 NHs located in
      France. Information on residents' health status (including dementia and pain
      assessment) and NHs' structure and organisation were recorded by the NH staff.
      The NH staff sent to the research team drug prescriptions participants were
      taking. They were screened for the use of analgesics (dependent variable) and
      other medications potentially used for pain management. The prevalence of
      analgesic use was 46.8% (42.3% for PWD and 52% for people with no dementia). A
      binary logistic regression showed that PWD (odds ratio 0.75; 95% confidence
      interval 0.66-0.85) and those who had no pain assessment records (odds ratio
      0.64; 95% confidence interval 0.53-0.79) had significant lower probabilities of
      taking analgesics; these results were independent of pain complaints. Results
      remained fairly unchanged after performing several sensitivity analyses. Our
      results suggest that improvements are needed in pain management in NHs,
      particularly for PWD. Implementing systematic evaluations of pain in NHs' routine
      would contribute to a better management of pain, which can lead to important
      benefits for residents.

PMID- 23872103
TI  - Effect of various kinds of cervical spinal surgery on clinical outcomes: a
      systematic review and meta-analysis.
AB  - The choice of a specific surgical technique should be based on its benefits and
      harms. Previous reviews have shown that the benefit of surgery over conservative
      care is not clearly demonstrated in patients with disorders of the cervical
      spine. Also, no additional benefit of fusion upon anterior decompression
      techniques could be found. A clear overview of other surgical techniques is
      lacking. We therefore aimed to assess the benefits and harms of cervical spinal
      surgery in patients with cervical disorders. We searched MEDLINE, EMBASE, CINAHL,
      and CENTRAL up to June 2012. Randomized controlled trials (RCTs) were selected
      which included adults with cervical disorders receiving a surgical intervention
      and that reported at least 1 clinically relevant outcome measure (eg, pain,
      function, recovery). Two authors independently assessed the risk of bias using
      the criteria recommended by the Cochrane Back Review Group and extracted the
      data. The quality of the evidence was rated using the GRADE method. We included
      39 RCTs comparing different surgical interventions. We found low-quality evidence
      for no difference in effectiveness between various surgical techniques used for
      anterior discectomy. There is a small, clinically irrelevant benefit on recovery
      and pain in favour of prosthetic disc surgery when compared with fusion
      techniques. Unfortunately, in these studies the authors had a clear conflict of
      interest. The differences in benefits and harms between the various surgical
      techniques are small. The surgeon, patient, and health care provider can
      therefore make the choice of any surgical technique based on experience,
      preferences, or costs. 

PMID- 23872104
TI  - Cognitive and affective reassurance and patient outcomes in primary care: a
      systematic review.
AB  - In the context of uncertainty about aetiology and prognosis, good clinical
      practice commonly recommends both affective (creating rapport, showing empathy)
      and cognitive reassurance (providing explanations and education) to increase self
      management in groups with nonspecific pain conditions. The specific impact of
      each of these components in reference to patients' outcomes has not been studied.
      This review aimed to systematically evaluate the evidence from prospective
      cohorts in primary care that measured patient-practitioner interactions with
      reference to patient outcomes. We carried out a systematic literature search and
      appraisal of study methodology. We extracted measures of affective and cognitive
      reassurance in consultations and their associations with consultation exit and
      follow-up measures of patients' outcomes. We identified 16 studies from 16,059
      abstracts. Eight studies were judged to be high in methodological quality.
      Pooling could not be achieved as a result of heterogeneity of samples and
      measures. Affective reassurance showed inconsistent findings with consultation
      exit outcomes. In 3 high-methodology studies, an association was found between
      affective reassurance and higher symptom burden and less improvement at follow
      up. Cognitive reassurance was associated with higher satisfaction and enablement
      and reduced concerns directly after the consultations in 8 studies; with
      improvement in symptoms at follow-up in 7 studies; and with reduced health care
      utilization in 3 studies. Despite limitations, there is support for the notion
      that cognitive reassurance is more beneficial than affective reassurance. We
      present a tentative model based on these findings and propose priorities for
      future research. 

PMID- 23872105
TI  - Couple perceptions of fibromyalgia symptoms: the role of communication.
AB  - The objectives of the current study were to describe fibromyalgia patient-spouse
      incongruence regarding patient pain, fatigue, and physical function; and to
      examine the associations of individual and interpersonal factors with patient
      spouse incongruence. Two hundred four fibromyalgia patients and their coresiding
      partners rated the patient's symptoms and function. Multilevel modeling revealed
      that spouses, on average, rated patient fatigue significantly lower than
      patients. Couple incongruence was not significantly different from zero, on
      average, for pain severity, interference, or physical function. However, there
      was significant variability across couples in how they rated the severity of
      symptoms and function, and how much incongruence existed within couples.
      Controlling for individual factors, patient and spouse reports of communication
      problems were significantly associated with levels of couple incongruence
      regarding patient fatigue and physical function, albeit in opposing directions.
      Across couples, incongruence was high when patients rated communication problems
      as high; incongruence was low when spouses rated communication problems as high.
      An important within-couple interaction was found for pain interference,
      suggesting that couples who are similar on level of communication problems
      experience low incongruence; those with disparate ratings of communication
      problems experience high incongruence. Findings suggest the important roles of
      spouse response and the patient's perception of how well the couple is
      communicating. Couple-level interventions targeting communication or other
      interpersonal factors may help to decrease incongruence and lead to better
      patient outcomes. 

PMID- 23872106
TI  - Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated
      with spatial working memory impairment in rats with inflammatory pain.
AB  - The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form
      interconnected neural circuits that are important for spatial cognition and
      memory, but it is not known whether the functional connectivity between these
      areas is affected by the onset of an animal model of inflammatory pain. To
      address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC
      and MD of adult rats and recorded local field potential activity during a food
      reinforced spatial working memory task. Recordings were performed for 3weeks,
      before and after the establishment of the pain model. Our results show that
      inflammatory pain caused an impairment of spatial working memory performance that
      is associated with changes in the activity of the mPFC-MD circuit; an analysis of
      partial directed coherence between the areas revealed a global decrease in the
      connectivity of the circuit. This decrease was observed over a wide frequency
      range in both the frontothalamic and thalamofrontal directions of the circuit,
      but was more evident from MD to mPFC. In addition, spectral analysis revealed
      significant oscillations of power across frequency bands, namely with a strong
      theta component that oscillated after the onset of the painful condition.
      Finally, our data revealed that chronic pain induces an increase in theta/gamma
      phase coherence and a higher level of mPFC-MD coherence, which is partially
      conserved across frequency bands. The present results demonstrate that functional
      disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain
      related working memory. 

PMID- 23872107
TI  - Oxytocin eliminates the own-race bias in face recognition memory.
AB  - The neuropeptide Oxytocin influences a number of social behaviors, including
      processing of faces. We examined whether Oxytocin facilitates the processing of
      out-group faces and reduce the own-race bias (ORB). The ORB is a robust
      phenomenon characterized by poor recognition memory of other-race faces compared
      to the same-race faces. In Experiment 1, participants received intranasal
      solutions of Oxytocin or placebo prior to viewing White and Black faces. On a
      subsequent recognition test, whereas in the placebo condition the same-race faces
      were better recognized than other-race faces, in the Oxytocin condition Black and
      White faces were equally well recognized, effectively eliminating the ORB. In
      Experiment 2, Oxytocin was administered after the study phase. The ORB resulted,
      but Oxytocin did not significantly reduce the effect. This study is the first to
      show that Oxytocin can enhance face memory of out-group members and underscore
      the importance of social encoding mechanisms underlying the own-race bias. This
      article is part of a Special Issue entitled Oxytocin and Social Behav. 

PMID- 23872108
TI  - The ultrastructure of the striated muscles of Derocheilocaris typica
      (Mystacocarida, Crustacea).
AB  - The striated muscles of Derocheilocaris typica consist of mononucleated cells,
      each containing one filament bundle. Large muscles consist of two or more cells
      adjacent to each other. The mitochondria line up along the filament bundle on one
      side. The nucleus is situated in the mitochondrial row and has a small
      cytoplasmic area around it filled with glycogen. The sarcomeres are between 3 and
      6 MUm long. The Z-line and H band are present. Six thin filaments surround one
      thick filament. All muscles belong to the phasic type. The tubular system
      emanates from the ends of the muscle cell and penetrates the whole cell. The
      tubules are formed as cisterns, which also open at the cell membrane at the level
      of the I bands. They have sarcoplasmic cisterns on both sides forming a
      continuous triad system. Partially transformed epidermal cells mediate muscle
      insertions on the cuticle. Tendons are formed with the transformed epidermal
      cells being supplemented by fibroblasts forming collagen fibers. Dorsal and
      ventral abdominal muscles are innervated from the dorso-lateral nerve arising
      from the nerve chain. Each muscle cell receives one axon, which forms one synapse
      on the mitochondrial-free side of the muscles. Axons form terminal spines, which
      make axo-axonal synapses.

PMID- 23872109
TI  - The morphogenesis of spermathecae and spermathecal glands in Drosophila
      melanogaster.
AB  - Sperm storage in female insects is important for reproductive success and sperm
      competition. In Drosophila melanogaster females, sperm viability during storage
      is dependent upon secretions produced by spermathecae and parovaria. Class III
      dermal glands are present in both structures. Spermathecal glands are initially
      comprised of a three-cell unit that is refined to a single secretory cell in the
      adult. It encapsulates an end-apparatus joining to a cuticular duct passing
      secretions to the spermathecal lumen. We have examined spermatheca morphogenesis
      using DIC and fluorescence microscopy. In agreement with a recent study, cell
      division ceases by 36 h after puparium formation (APF). Immunostaining of the
      plasma membrane at this stage demonstrates that gland cells wrap around the
      developing end-apparatus and each other. By 48-60 h APF, the secretory cell
      exhibits characteristic adult morphology of an enlarged nucleus and extracellular
      reservoir. A novel finding is the presence of an extracellular reservoir in the
      basal support cell that is continuous with the secretory cell reservoir. Some
      indication of early spermathecal gland formation is evident in the division of
      enlarged cells lying adjacent to the spermathecal lumen at 18 h APF and in
      cellular processes that bind clusters of cells between 24 and 30 h APF.

PMID- 23872110
TI  - Surgical outcomes and national comprehensive cancer network compliance in
      advanced ovarian cancer surgery in a low volume military treatment facility.
AB  - OBJECTIVE: To evaluate the optimal cytoreduction (OPT) rate, National
      Comprehensive Cancer Network (NCCN) treatment guideline compliance rate and
      patient outcomes for advanced stage epithelial ovarian cancer (EOC) patients at
      our low volume institution. METHODS: Following IRB approval, records of patients
      with Stage III-IV EOC, primary peritoneal, or fallopian tube carcinoma completing
      both primary surgery and adjuvant chemotherapy were reviewed. Patient
      demographics, clinicopathologic variables, cytoreduction status (optimal or
      suboptimal), NCCN treatment guideline compliance, and survival were reviewed.
      Standard statistical tests including the t-test, Chi-square or Fisher's exact
      test and Kaplan-Meier Survival curves were utilized. RESULTS: Overall, 48
      patients met all inclusion criteria. 35(73%) and 13 (27%) achieved optimal and
      suboptimal cytoreduction, respectively. Median overall survival (OS) for all
      patients was 37.1 months (95% CI 23.2 - 51.1 months) and NCCN treatment guideline
      compliance was 85.4%. Compared to sub-optimally cytoreduced patients the
      optimally cytoreduced patients were significantly older (62.2 vs. 53.5 yrs;
      p=0.015); no other significant clinicopathologic differences were observed
      between the two groups. 19 of 48 (39.6%) patients enrolled in an upfront
      cooperative group trial. Median OS was 43.4 months for optimally compared to 15.6
      months in sub-optimally cytoreduced patients (p=0.012). CONCLUSIONS: NCCN
      treatment guideline compliance, OPT, and median OS rates in our low volume
      institution are similar to those reported nationally, and argue against using
      volume alone as a rationale for centralization of care.

PMID- 23872111
TI  - Etiology of vulvar cancer will impact on treatment options and therapy outcome:
      Two major pathways of vulvar cancer.

PMID- 23872112
TI  - Glutathione peroxidase contributes with heme oxygenase-1 to redox balance in
      mouse brain during the course of cerebral malaria.
AB  - Oxidative stress has been attributed both a key pathogenic and rescuing role in
      cerebral malaria (CM). In a Plasmodium berghei ANKA murine model of CM, host
      redox signaling and functioning were examined during the course of neurological
      damage. Host antioxidant defenses were early altered at the transcriptional level
      indicated by the gradually diminished expression of superoxide dismutase-1 (sod
      1), sod-2, sod-3 and catalase genes. During severe disease, this led to the
      dysfunctional activity of superoxide dismutase and catalase enzymes in damaged
      brain regions. Vitagene associated markers (heat shock protein 70 and thioredoxin
      1) also showed a decaying expression pattern that paralleled reduced expression
      of the transcription factors Parkinson disease 7, Forkhead box O 3 and X-box
      binding protein 1 with a role in preserving brain redox status. However, the
      oxidative stress markers reactive oxygen/nitrogen species were not accumulated in
      the brains of CM mice and redox proteomics and immunohistochemistry failed to
      detect quantitative or qualitative differences in protein carbonylation. Thus,
      the loss of antioxidant capacity was compensated for in all cerebral regions by
      progressive upregulation of heme oxygenase-1, and in specific regions by early
      glutathione peroxidase-1 induction. This study shows for the first time a
      scenario of cooperative glutathione peroxidase and heme oxygenase-1 upregulation
      to suppress superoxide dismutase, catalase, heat shock protein-70 and thioredoxin
      1 downregulation effects in experimental CM, counteracting oxidative damage and
      maintaining redox equilibrium. Our findings reconcile the apparent inconsistency
      between the lack of oxidative metabolite build up and reported protective effect
      of antioxidant therapy against CM.

PMID- 23872113
TI  - Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4
      signaling in macrophages.
AB  - Polyphenolic compounds have been found to possess a wide range of physiological
      activities that may contribute to their beneficial effects against inflammation
      related diseases; however, the molecular mechanisms underlying this anti
      inflammatory activity are not completely characterized, and many features remain
      to be elucidated. In this study, we investigated the molecular basis for the down
      regulation of toll-like receptor 4 (TLR4) signal transduction by procyanidin
      dimer B2 (Pro B2) in macrophages. Pro B2 markedly elevated the expression of the
      interleukin (IL)-1 receptor-associated kinase (IRAK)-M protein, a negative
      regulator of TLR signaling. Lipopolysaccharide (LPS)-induced expression of cell
      surface molecules (CD80, CD86, and MHC class I/II) and production of pro
      inflammatory cytokines (tumor necrosis factor-alpha, IL-1beta, IL-6, and IL
      12p70) were inhibited by Pro B2, and this action was prevented by IRAK-M
      silencing. In addition, Pro B2-treated macrophages inhibited LPS-induced
      activation of mitogen-activated protein kinases such as extracellular signal
      regulated kinase 1/2, p38, and c-Jun N-terminal kinase and the translocation of
      nuclear factor kappaB and p65 through IRAK-M. We also found that Pro B2-treated
      macrophages inactivated naive T cells by inhibiting LPS-induced interferon-gamma
      and IL-2 secretion through IRAK-M. These novel findings provide new insights into
      the understanding of negative regulatory mechanisms of the TLR4 signaling pathway
      and the immune-pharmacological role of Pro B2 in the immune response against the
      development and progression of many chronic diseases. 

PMID- 23872114
TI  - The Kunitz-protease inhibitor domain in amyloid precursor protein reduces
      cellular mitochondrial enzymes expression and function.
AB  - Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and
      this can be contributed by aberrant metabolic enzyme function. But, the mechanism
      causing this enzymatic impairment is unclear. Amyloid precursor protein (APP) is
      known to be alternatively spliced to produce three major isoforms in the brain
      (APP695, APP751, APP770). Both APP770 and APP751 contain the Kunitz Protease
      Inhibitory (KPI) domain, but the former also contain an extra OX-2 domain. APP695
      on the other hand, lacks both domains. In AD, up-regulation of the KPI-containing
      APP isoforms has been reported. But the functional contribution of this elevation
      is unclear. In the present study, we have expressed and compared the effect of
      the non-KPI containing APP695 and the KPI-containing APP751 on mitochondrial
      function. We found that the KPI-containing APP751 significantly decreased the
      expression of three major mitochondrial metabolic enzymes; citrate synthase,
      succinate dehydrogenase and cytochrome c oxidase (COX IV). This reduction lowers
      the NAD(+)/NADH ratio, COX IV activity and mitochondrial membrane potential.
      Overall, this study demonstrated that up-regulation of the KPI-containing APP
      isoforms is likely to contribute to the impairment of metabolic enzymes and
      mitochondrial function in AD.

PMID- 23872115
TI  - Targeted deletion of Kif18a protects from colitis-associated colorectal (CAC)
      tumors in mice through impairing Akt phosphorylation.
AB  - Kinesins are a superfamily of molecular motors involved in cell division or
      intracellular transport. They are becoming important targets for chemotherapeutic
      intervention of cancer due to their crucial role in mitosis. Here, we demonstrate
      that the kinesin-8 Kif18a is overexpressed in murine CAC and is a crucial
      promoter during early CAC carcinogenesis. Kif18a-deficient mice are evidently
      protected from AOM-DSS-induced colon carcinogenesis. Kif18A is responsible for
      proliferation of colonic tumor cells, while Kif18a ablation in mice promotes cell
      apoptosis. Mechanistically, Kif18a is responsible for induction of Akt
      phosphorylation, which is known to be associated with cell survival regulation.
      In conclusion, Kif18a is critical for colorectal carcinogenesis in the setting of
      inflammation by mechanisms of increased PI3K-AKT signaling. Inhibition of Kif18A
      activity may be useful in the prevention or chemotherapeutic intervention of CAC.

PMID- 23872116
TI  - Expectorant and antioxidant activities of purified fumarprotocetraric acid from
      Cladonia verticillaris lichen in mice.
AB  - The lichen Cladonia verticillaris produces bioactive secondary metabolites, such
      as fumarprotocetraric (FUM) and protocetraric acids. Species of the genus
      Cladonia demonstrate anti-tumor, anti-inflammatory and antipyretic activities and
      have been used in folk medicine to treat respiratory diseases (throat irritation,
      cough, asthma and tuberculosis). The aim of the present study was to evaluate the
      expectorant and mucolytic activities of fumarprotocetraric acid in albino Swiss
      mice. FUM was extracted and purified from an acetone extract of C. verticillaris.
      The phenol red quantification method was used on the bronchoalveolar lavage fluid
      following the administration of FUM (25, 50 or 100 mg/kg orally or
      intraduodenally and 12.5, 25 or 50 mg/kg, intraperitoneally) for the evaluation
      of expectorant activity. Control groups received either saline solution (7.5
      mL/kg) or ambroxol (1 mg/kg) through the same administration routes. Antioxidant
      activity was evaluated using the thiobarbituric acid reactive species assay in
      mouse lung tissue treated with the FUM at 25, 50 or 100 mg/kg orally, followed by
      a lipopolysaccharide solution at 1 mg/kg intrapleurally. The same protocol was
      used for the control groups using either saline solution (7.5 mL/kg, orally) or N
      acetylcysteine (20 mg/kg, orally). RESULTS: Orally administered FUM at doses of
      25 and 50 mg/kg promoted significantly greater dose-dependent phenol red activity
      in the bronchoalveolar lavage and expectorant activity in comparison to the
      controls (p < 0.05). Lipid peroxidation (malondialdehyde equivalent) was reduced
      by 50% in the lung tissue. CONCLUSION: The results confirm the expectorant and
      antioxidant properties of fumarprotocetraric acid produced by the lichen C.
      verticillaris.

PMID- 23872118
TI  - Cure by fiat?

PMID- 23872117
TI  - Offset analgesia is reduced in older adults.
AB  - Recent studies indicate that aging is associated with dysfunctional changes in
      pain modulatory capacity, potentially contributing to increased incidence of pain
      in older adults. However, age-related changes in offset analgesia (offset), a
      form of temporal pain inhibition, remain poorly characterized. The purpose of
      this study was to investigate age differences in offset analgesia of heat pain in
      healthy younger and older adults. To explore the peripheral mechanisms underlying
      offset, an additional aim of the study was to test offset at 2 anatomical sites
      with known differences in nociceptor innervation. A total of 25 younger adults
      and 20 older adults completed 6 offset trials in which the experimental heat
      stimulus was presented to the volar forearm and glabrous skin of the palm. Each
      trial consisted of 3 continuous phases: an initial 15-second painful stimulus
      (T1), a slight increase in temperature from T1 for 5 seconds (T2), and a slight
      decrease back to the initial testing temperature for 10 seconds (T3). During each
      trial, subjects rated pain intensity continuously using an electronic visual
      analogue scale (0-100). Older adults demonstrated reduced offset compared to
      younger adults when tested on the volar forearm. Interestingly, offset analgesia
      was nonexistent on the palm for all subjects. The reduced offset found in older
      adults may reflect an age-related decline in endogenous inhibitory systems.
      However, although the exact mechanisms underlying offset remain unknown, the
      absence of offset at the palm suggests that peripheral mechanisms may be involved
      in initiating this phenomenon.

PMID- 23872119
TI  - A two year study of verified spider bites in Switzerland and a review of the
      European spider bite literature.
AB  - During a two-year study, all spider bites recorded by Swiss primary care
      physicians were reported to the Swiss Toxicological Information Centre and all
      collected spiders were identified. A total of 14 verified spider bites were
      recorded, involving five species from four families: Zoropsis spinimana (five
      cases), Cheiracanthium punctorium (four cases), Tegenaria atrica (three cases)
      and one case of Malthonica ferruginea (= Tegenaria ferruginea) (both Agelenidae),
      and one case of Amaurobius ferox (Amaurobiidae). The bites of all spider species
      produced relatively mild symptoms. Local symptoms such as moderate to severe
      pain, circumscribed swelling and redness were the only effects in most cases.
      Systemic symptoms were rare. There was complete recovery in all cases and all
      lesions healed completely without further damage or secondary disorders.
      Following a review of the European spider bite literature, the number of spider
      species capable of biting humans in Europe is considered to be much larger than
      could be concluded from this study. Most spider bites are restricted to species
      living synanthropically, thus promoted by climate and habitat change. The annual
      frequency of spider bites in Switzerland is estimated at 10-100 bites per million
      inhabitants, but this is predicted to increase due to the continuous arrival of
      new alien species, many of which have a high potential to establish in urban
      areas. 

PMID- 23872120
TI  - The milk widow spider? Repeated misspelling of the widow spider genus Latrodectus
      as "Lactrodectus".

PMID- 23872121
TI  - Biochemical and preliminary X-ray characterization of the tumor-associated
      calcium signal transducer 2 (Trop2) ectodomain.
AB  - Trop2 is a stem/progenitor cell marker, which is also upregulated in several
      human carcinomas. The largest part of the molecule, recognized by several
      monoclonal antibodies, is represented by the extracellular part (ectodomain) and
      is composed of three modules. The aim of our work was to prepare the ectodomain
      of Trop2 in quantities sufficient for structural and functional studies. We used
      the Spodoptera frugiperda (Sf9) insect cell expression system to prepare the
      Trop2 ectodomain (Trop2EC) in two forms - wt glycosylated (gTrop2EC) and mutant
      non-glycosylated form (Trop2EC(Delta/N)). Recombinant protein was purified from
      cell culture supernatants using two subsequent nickel ion-affinity
      chromatographies with a final yield of 15-17mg of purified recombinant protein
      per liter of culture. Size-exclusion chromatography together with MALS and
      chemical crosslinking were used to demonstrate for the first time that the Trop2
      ectodomain forms a dimer. Both gTrop2EC and Trop2EC(Delta/N) exhibit similar
      biochemical properties, however the solubility of Trop2EC(Delta/N) is much lower
      (less than 1mg/ml). For the purpose of structural studies, we crystallized the
      glycosylated form gTrop2EC. The native dataset was collected with a resolution of
      2.94A and will be used in ongoing work for phasing and structure solution to
      further understand the role of Trop2 and the structure-function relation between
      Trop2 and the epithelial cell adhesion molecule (EpCAM).

PMID- 23872122
TI  - Part I: The application of the h-index to groups of individuals and departments
      in academic neurosurgery.
AB  - OBJECTIVE: The h-index was introduced as a means of quantifying the contribution
      a researcher makes to the scientific literature. We evaluated the h-index for
      academic neurosurgeons to assess the various methods of calculation and to
      determine whether the h-index can be used to differentiate groups of individuals
      by various classifications. METHODS: The h-index was calculated for all
      neurosurgeons from 10 institutions ranked highly by 2012 U.S. News & World Report
      plus the authors' institution via Scopus. The h-index also was calculated
      manually to evaluate its accuracy. The average h-index was calculated for groups
      on the basis of sex, academic rank, years in practice, institution, and
      subspecialty. Cumulative and mean h-indices were calculated for each department.
      RESULTS: The median h-index for the 188 neurosurgeons was 16 (mean, 19.71; range,
      0-61). There was a positive association between the h-index, academic rank, and
      years posttraining. There was a significant difference between the "manually
      calculated" and automated h-indices, particularly for more senior physicians. The
      difference in h-index between men and women was not statistically significant.
      Among subspecialties, vascular surgeons had the greatest average h-index and
      general neurosurgeons had the lowest. There were significant shifts in
      departmental rankings when the cumulative or mean departmental indices were
      compared with the U.S. News & World Report rankings. CONCLUSION: Application of
      the h-index as a bibliometric in neurosurgery can distinguish academic
      productivity on the basis of academic rank, years posttraining, and neurosurgical
      subspecialties. The application of the h-index to compare departments is
      problematic and, at this time, not reliable.

PMID- 23872123
TI  - Aggregates of nisin with various bactoprenol-containing cell wall precursors
      differ in size and membrane permeation capacity.
AB  - Many lantibiotics use the membrane bound cell wall precursor Lipid II as a
      specific target for killing Gram-positive bacteria. Binding of Lipid II usually
      impedes cell wall biosynthesis, however, some elongated lantibiotics such as
      nisin, use Lipid II also as a docking molecule for pore formation in bacterial
      membranes. Although the unique nisin pore formation can be analyzed in Lipid II
      doped vesicles, mechanistic details remain elusive. We used optical sectioning
      microscopy to directly visualize the interaction of fluorescently labeled nisin
      with membranes of giant unilamellar vesicles containing Lipid II and its various
      bactoprenol precursors. We quantitatively analyzed the binding and permeation
      capacity of nisin when applied at nanomolar concentrations. Specific interactions
      with Lipid I, Lipid II and bactoprenol-diphosphate (C55-PP), but not bactoprenol
      phosphate (C55-P), resulted in the formation of large molecular aggregates. For
      Lipid II, we demonstrated the presence of both nisin and Lipid II in these
      aggregates. Membrane permeation induced by nisin was observed in the presence of
      Lipid I and Lipid II, but not in the presence of C55-PP. Notably, the size of the
      C55-PP-nisin aggregates was significantly smaller than that of the aggregates
      formed with Lipid I and Lipid II. We conclude that the membrane permeation
      capacity of nisin is determined by the size of the bactoprenol-containing
      aggregates in the membrane. Notably, transmitted light images indicated that the
      formation of large aggregates led to a pinch-off of small vesicles, a mechanism,
      which probably limits the growth of aggregates and induces membrane leakage. 

PMID- 23872124
TI  - Can proton pumping by SERCA enhance the regulatory role of phospholamban and
      sarcolipin?
AB  - The effect of the incorporation of phosphorylated phospholamban (pPLN) and
      sarcolipin (SLN) in mercury-supported self-assembled lipid monolayers and in
      lipid bilayers tethered to mercury via a hydrophilic spacer was investigated by
      voltammetric techniques and electrochemical impedance spectroscopy. It was shown
      that pPLN and SLN do not permeabilize lipid bilayers toward ions at physiological
      pH. However, they exert a permeabilizing action toward inorganic monovalent
      cations such as K(+) and Tl(+), but not toward divalent cations such as Ca(2+)
      and Cd(2+), following a small decrease in pH. This behavior can be associated
      with their regulatory action on the Ca-ATPase of the sarcoplasmic reticulum
      (SERCA). SERCA pumps two Ca(2+) ions from the cytosol to the lumen of the
      sarcoplasmic reticulum (SR) and two protons in the opposite direction, causing a
      transient decrease of pH in the immediate vicinity of its cytoplasmic domain.
      This decrease is expected to activate the liberated pPLN molecules and SLN to
      make the SR membrane leakier toward K(+) and Na(+) and the SLN ion channel to
      translocate small inorganic anions, such as Cl(-). The effect of pPLN and SLN,
      which becomes synergic when they are both present in the SR membrane, is expected
      to favor a rapid equilibration of ions on both sides of the membrane. 

PMID- 23872126
TI  - Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of
      intoxication treatment by alpha-tocopherol acetate and methylene blue.
AB  - OBJECTIVES: Investigation of hydroxylamine sulfate toxicity mechanism in vivo and
      estimation of alpha-tocopherol acetate and methylene blue efficiency in poisoning
      treatments. METHODS: In vivo experiments were conducted on 102 Wistar Han rats.
      The experiments investigated the hematotoxic and oxidative stress effects of
      hydroxylamine sulfate in acute and subacute toxicity treatment of animals.
      Electron Spin Resonance was used for quantitative determination of blood and
      liver tissue parameters alterations after intoxication. The osmotic fragility of
      erythrocytes, lipid peroxidation intensity and level of SH-groups in liver of
      rats were determined by established biochemical assays. RESULTS: Hydroxylamine
      sulfate cause an acute hematotoxicity and oxidative stress in vivo as
      demonstrated by the appearance of free oxidized iron in blood, reduced
      glutathione content and increased lipid peroxidation in liver. The experimental
      studies showed the formation of Hb-NO, MetHb in erythrocytes and as well of
      stable complex of reduced iron (Fe(2+)) with hydroxylamine sulfate. Methylene
      blue treatment does not reduce the Hb-NO or MetHb levels in intoxicated animals
      while administration of alpha-tocopherol acetate reduces substantially lipid
      peroxidation. CONCLUSIONS: Oxidative stress is a key mechanism of acute
      hematotoxicity caused by hydroxylamine sulfate. Methylene blue is not suitable
      antidote in case of hydroxylamine intoxication.

PMID- 23872125
TI  - Effects of Bacillus subtilis ANSB060 on growth performance, meat quality and
      aflatoxin residues in broilers fed moldy peanut meal naturally contaminated with
      aflatoxins.
AB  - This study was conducted to investigate the toxic effects of aflatoxins and the
      efficacy of Bacillus subtilis ANSB060 for the amelioration of aflatoxicosis in
      broiler chickens. Six replicates of ten broilers each were assigned to one of
      seven dietary treatments, which were labeled C0 (basal diet); M0 (basal diet
      containing moldy peanut meal); C500 and C1000 (C0+500 or 1000 g/t aflatoxin
      biodegradation preparations, composed mainly of ANSB060); and M500, M1000 and
      M2000 (M0+500, 1000 or 2000 g/t aflatoxin biodegradation preparations). The
      concentrations of aflatoxin B1, B2, G1 and G2 in the moldy diets (M0, M500, M100
      and M2000) fluctuated around 70.7+/-1.3, 11.0+/-1.5, 6.5+/-0.8 and 2.0+/-0.3
      MUg/kg, respectively. The results showed that the M0 diet caused a significant
      decrease in average daily weight gain and increased feed requirements, with a
      gain ratio increasing from d 8 to 42, deterioration in meat quality and aflatoxin
      residues in broilers' livers as compared with the C0 diet. The addition of
      ANSB060 to the aflatoxin-contaminated diets offset these negative effects,
      leading to the conclusion that ANSB060 has a protective effect on growth
      performance and meat quality while reducing the amount of aflatoxin residues in
      the livers of broilers fed naturally moldy peanut meal.

PMID- 23872127
TI  - Subchronic perinatal asphyxia in rats: embryo-foetal assessment of a new model of
      oxidative stress during critical period of development.
AB  - Approximately 3% of annual births suffer from birth asphyxia and one million of
      these newborns die. The aim of this study was to develop a model for studying
      subchronic perinatal asphyxia (SPA) in rats. Pregnant animals were exposed to
      10.5% O2 during sensitive stages of brain development for 4h a day. Biochemical
      variables were analysed immediately and 24h after asphyxia. SPA caused
      significant reduction of foetal weight, produced abnormalities of distal parts of
      the skeleton, and anomalies in the development of brain ventricles. Time
      dependent changes were observed in several parameters indicating adjustment of
      the developing organism to the delivery. Whereas lactate was elevated immediately
      after asphyxia, glucose mirrored high energy needs 24h after the insult.
      Immunohistochemical examination of the placentas revealed overgrowth of acidic
      glycoconjugates in the extracellular matrix of vascular walls in the animals
      exposed to asphyxia. We observed the presence of muscle fibres in chorionic plate
      arteries and also in intraplacental arteries. The present model proved to be
      useful for the study of asphyxial conditions during pregnancy. As it is non
      invasive and allows to control asphyxial conditions, it appears suitable for the
      screening and investigation of indicators of asphyxia in the mother and foetus. 

PMID- 23872128
TI  - Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic
      diseases.
AB  - Resveratrol-a natural polyphenolic compound-was first discovered in the 1940s.
      Although initially used for cancer therapy, it has shown beneficial effects
      against most cardiovascular and cerebrovascular diseases. A large part of these
      effects are related to its antioxidant properties. Here we review: (a) the
      sources, the metabolism, and the bioavailability of resveratrol; (b) the ability
      of resveratrol to modulate redox signalling and to interact with multiple
      molecular targets of diverse intracellular pathways; (c) its protective effects
      against oxidative damage in cardio-cerebro-vascular districts and metabolic
      disorders such as diabetes; and (d) the evidence for its efficacy and toxicity in
      humans. The overall aim of this review is to discuss the frontiers in the field
      of resveratrol's mechanisms, bioactivity, biology, and health-related use.

PMID- 23872129
TI  - Wogonin attenuates etoposide-induced oxidative DNA damage and apoptosis via
      suppression of oxidative DNA stress and modulation of OGG1 expression.
AB  - Damage to DNA can lead to many different acute and chronic pathophysiological
      conditions, ranging from cancer to endothelial damage. The current study has been
      initiated to determine whether the flavonoid wogonin can attenuate etoposide
      induced oxidative DNA damage and apoptosis in mouse bone marrow cells. We found
      that oral administration of wogonin before etoposide injection significantly
      attenuates etoposide-induced oxidative DNA damage and apoptosis in a dose
      dependent manner. Etoposide induced a significant down-regulation of mRNA
      expression of the OGG1 repair gene and marked biochemical alterations
      characteristic of oxidative DNA stress, including increased 8-OHdG, enhanced
      lipid peroxidation and reduction in reduced glutathione. Prior administration of
      wogonin ahead of etoposide challenge restored these altered parameters.
      Importantly, wogonin had no antagonizing effect on etoposide-induce topoisomerase
      II inhibition. Conclusively, our study indicates that wogonin has a protective
      role in the abatement of etoposide-induced oxidative DNA damage and apoptosis in
      the bone marrow cells of mice via suppression of oxidative DNA stress and
      enhancing DNA repair through modulation of OGG1 repair gene expression.
      Therefore, wogonin can be a promising chemoprotective agent and might be useful
      to avert secondary leukemia and other drug-related cancers in cured cancer
      patients and medical personnel exposing to the potent carcinogen etoposide. 

PMID- 23872130
TI  - Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance
      and dysfunction in rats.
AB  - Dietary intake of fructose and sucrose can cause development of metabolic and
      cardiovascular disorders. The consequences of high-fructose corn syrup (HFCS), a
      commonly consumed form of fructose and glucose, have poorly been examined.
      Therefore, in this study, we investigated whether HFCS intake (10% and 20%
      beverages for 12 weeks) impacts vascular reactivity to insulin and endothelin-1
      in conjunction with insulin receptor substrate-1(IRS-1), endothelial nitric oxide
      synthase (eNOS) and inducible NOS (iNOS) mRNA/proteins levels in aorta of rats.
      At challenge, we tested the effectiveness of resveratrol (28-30 mg/kg body
      weight/day) on outcomes of HFCS feeding. HFCS (20%) diet feeding increased plasma
      triglyceride, VLDL, cholesterol, insulin and glucose levels, but not body weights
      of rats. Impaired nitric oxide-mediated relaxation to insulin (10-9 to 3*10-6 M),
      and enhanced contraction to endothelin-1 (10-11 to 10-8 M) were associated with
      decreased expression of IRS-1 and eNOS mRNA and protein, but increased expression
      of iNOS, in aortas of rats fed with HFCS. Resveratrol supplementation restored
      many features of HFCS-induced disturbances, probably by regulating eNOS and iNOS
      production. In conclusion, dietary HFCS causes vascular insulin resistance and
      endothelial dysfunction through attenuating IRS-1 and eNOS expressions as well as
      increasing iNOS in rats. Resveratrol has capability to recover HFCS-induced
      disturbances.

PMID- 23872131
TI  - Kinetics and metabolism of the Fusarium toxin deoxynivalenol in farm animals:
      consequences for diagnosis of exposure and intoxication and carry over.
AB  - The knowledge of factors influencing the kinetics, metabolism and bioavailability
      of the Fusarium toxin deoxynivalenol (DON) is a basic prerequisite for evaluation
      of the transfer (carry over) of the toxin and its metabolites into edible
      tissues, and for a physiological specimen-based diagnosis of intoxication. These
      aspects are addressed in the present review, and potentials and pitfalls of the
      suitability of analysis of physiological samples for evaluation of the DON
      exposure as a veterinary tool are discussed. For example, the farm animal species
      was shown to be a determining factor influencing the metabolic profile and the
      bioavailability of DON. Although linear relationships were derived between DON
      exposure of ad libitum and restrictively fed animals and DON or de-epoxy-DON
      concentration in the blood of pigs, dairy cows and sheep, it has to be considered
      that individual values might markedly deviate from these relationships, which
      makes interpretation of measured concentrations of DON and its metabolites
      difficult. The situation is further complicated by the lack of established
      relationships between DON residues in physiological matrices and the adverse
      effects of DON on the health and performance of farm animals. 

PMID- 23872132
TI  - Dermal absorption and hydrolysis of methylparaben in different vehicles through
      intact and damaged skin: using a pig-ear model in vitro.
AB  - Currently, there is a trend to reduce of parabens use due to concern about the
      safety of their unmetabolised forms. This paper focused on dermal absorption rate
      and effectiveness of first-pass biotransformation of methylparaben (MP) under in
      use conditions of skincare products. 24-h exposure of previously frozen intact
      and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP
      (AD, applied dose of 10 MUg/cm2), resulted in 2.0-5.8%AD and 2.9-7.6%AD of
      unmetabolised MP, and 37.0-73.0%AD and 56.0-95.0%AD of p-hydroxybenzoic acid,
      respectively, in the receptor fluid. The absorption rate of MP was higher from
      emulsions than from hydrogels, from enhancer-containing vehicles than from
      enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the
      freezing of pig-ear skin slightly reduces hydrolysis of MP. After 4-h exposure of
      intact freshly excised and intact frozen stored skin, amount of <LOQ-2.3%AD and
      2.3-3.3%AD unmetabolised MP, respectively, were found in the receptor fluid.
      Taking into account the number of useful properties of MP, but also the potential
      of systemic availability of unmetabolised MP, we consider that MP is more
      suitable for preserving rinse-off topical products than for leave-on products.
      Risk of systemic absorption of parabens should also be explored via the skin with
      damaged barrier.

PMID- 23872133
TI  - Vitamin B2: a promising adjuvant in cisplatin based chemoradiotherapy by cellular
      redox management.
AB  - Cancer has been a big challenge in the clinical research arena for many years.
      All the major anticancer drugs are either not effective or induce serious side
      effects. Cisplatin (CP) is one of the most valued anticancer drugs against
      various forms of cancer but it exerts many side effects often resulting in
      withdrawal of clinical usage during long-term chemotherapy. Thus, increasing the
      efficacy of the drugs and minimizing deleterious side effects is needed. Vitamins
      like riboflavin (RF) are promising under photodynamic therapy in this aspect
      because of its potential as an efficient adjuvant confirmed in many cancer cell
      lines and animal-based studies. It has been found to alleviate CP-induced side
      effects significantly under photoillumination in mice. As CP exerts most of its
      toxic effects by oxidative and nitrosative stress; clubbing ribophototherapy with
      chemotherapy involving CP can shift the redox status favoring better cancer
      treatment. This strategy can not only increase the average life span of the
      cancer patients but also improve their quality of life significantly. However,
      cancer is still considered as a disease of genetic and metabolic disorders;
      hence, attacking both aspects of the disease can give better results as compared
      to contemporary treatment modalities. 

PMID- 23872134
TI  - Dietary supplementation of Bifidobacterium longum strain AH1206 increases its
      cecal abundance and elevates intestinal interleukin-10 expression in the neonatal
      piglet.
AB  - Intestinal microbiota of infants differ in response to gestational age, delivery
      mode and feeding regimen. Dietary supplementation of probiotic bacteria is one
      method of promoting healthy populations. We examined the impact of a novel
      probiotic strain of Bifidobacterium longum (AH1206) on the health, growth and
      development of neonatal pigs as a model for infants. Day-old pigs were fed milk
      based formula containing AH1206 at 0, 109, or 1011 CFU/d for 18 d
      (n=10/treatment). Differences were not detected in growth, organ weights or body
      temperatures (P>0.1); however pigs fed the high dose showed a small (2%)
      reduction in feed intake. Bacterial translocation was not affected as indicated
      by total anaerobic and aerobic counts (CFU) in samples of spleen, liver and
      mesenteric lymph nodes (P>0.1). Feeding AH1206 had no effects on fecal
      consistency, but increased the density of B. longum in the cecum. Ileal TNF
      expression tended to increase (P=0.08) while IL-10 expression increased linearly
      (P=0.01) with supplementation. Based upon findings in the suckling piglet model,
      we suggest that dietary supplementation with B. longum (AH1206) may be safe for
      human infants based on a lack of growth, development or deleterious immune
      related effects observed in piglets.

PMID- 23872135
TI  - Neuronal nicotinic receptor agonists ameliorate spontaneous motor asymmetries and
      motor discoordination in a unilateral mouse model of Parkinson's disease.
AB  - The degeneration of the nigrostriatal dopamine (DA) system underlies the motor
      deficits in Parkinson's disease (PD). In recent years, epidemiological reports
      that smokers have lower incidences of PD have brought attention to the nicotinic
      acetylcholine system as a potential target for novel therapeutics. Nicotine, an
      agonist of neuronal nicotinic receptors (NNRs), modulates functions relevant to
      PD via stimulation of dopaminergic transmission in the nigrostriatal pathway,
      particularly via activation of alpha6beta2* and alpha4beta2* NNRs. Recently,
      reduced support of DA neurons by neurotrophic growth factors has been described
      in PD. Fibroblast growth factor (FGF) is critical for the development and
      protection of adult DA neurons. In FGF-2 knockout mice and the related th
      fgfr1(tk-) mouse model there is heightened sensitivity to DA neuronal oxidative
      neurotoxin 6-hydroxydopamine (6-OHDA). In the present study, FGF-deficient
      transgenic mice th-fgfr1(tk-) were used to analyze the effects of novel full (TC
      8831) and partial (TC-8581) agonists of beta2-containing nicotinic receptors on
      impaired motor behavior following unilateral 6-OHDA lesions. The lesions
      generated spontaneous (drug-naive) turning asymmetries that correlated
      exponentially with the depletion of DA biomarkers in the lesioned striata. These
      mice also exhibited a reduced capacity to remain on the accelerating rotarod.
      Oral administration of TC-8831, an NNR agonist with high specificity for beta2
      subunits and a full agonist at producing DA release from striatal synaptosomes,
      attenuated unidirectional turning and improved motor coordination. In contrast,
      partial beta2 NNR agonist TC-8581 had no effect on behaviors in this model. This
      study demonstrates the potential of NNR targeting-compounds to facilitate motor
      function in PD. 

PMID- 23872136
TI  - The antidepressant-like effect of bacopaside I: possible involvement of the
      oxidative stress system and the noradrenergic system.
AB  - In the present study, the antidepressant-like effect of bacopaside I, a saponin
      compound present in the Bacopa monniera plant, was evaluated by behavioral and
      neurochemical methods. Bacopaside I (50, 15 and 5 mg/kg) was given to mice via
      oral gavage for 7 successive days. The treatment significantly decreased the
      immobility time in mouse models of despair tests, but it did not influence
      locomotor activity. Neurochemical assays suggested that treatment by bacopaside I
      (50, 15 and 5 mg/kg) improved brain antioxidant activity to varying degrees after
      the behavioral despair test. Bacopaside I (15 and 5 mg/kg) significantly reversed
      reserpine-induced depressive-like behaviors, including low temperature and
      ptosis. Conversely, bacopaside I did not affect either brain MAO-A or MAO-B
      activity after the behavioral despair test in mice. Additionally, 5
      hydroxytryptophan (a precursor of 5-serotonin) was not involved in the
      antidepressant-like effect of bacopaside I. These findings indicated that the
      antidepressant-like effect of bacopaside I might be related to both antioxidant
      activation and noradrenergic activation, although the exact mechanism remains to
      be further elucidated.

PMID- 23872137
TI  - Assessment of mercury chloride-induced toxicity and the relevance of P2X7
      receptor activation in zebrafish larvae.
AB  - Zebrafish (Danio rerio) has been adopted as a model for behavioral, immunological
      and toxicological studies. Mercury is a toxic heavy metal released into the
      environment. There is evidence indicating that heavy metals can modulate
      ionotropic receptors, including the purinergic receptor P2X7. Therefore, this
      study evaluated the in vivo effects of acute exposure to mercury chloride (HgCl2)
      in zebrafish larvae and to investigate the involvement of P2X7R in mercury
      related toxicity. Larvae survival was evaluated for 24 h after exposure to HgCl2,
      ATP or A740003. The combination of ATP (1 mM) and HgCl2 (20 MUg/L) decreased
      survival when compared to ATP 1 mM. The antagonist A740003 (300 and 500 nM)
      increased the survival time, and reversed the mortality caused by ATP and HgCl2
      in association. Quantitative real time PCR showed a decrease of P2X7R expression
      in the larvae treated with HgCl2 (20 MUg/L). Evaluating the oxidative stress our
      results showed decreased CAT (catalase) activity and increased MDA
      (malondialdehyde) levels. Of note, the combination of ATP with HgCl2 showed an
      additive effect. This study provides novel evidence on the possible mechanisms
      underlying the toxicity induced by mercury, indicating that it is able to
      modulate P2X7R in zebrafish larvae.

PMID- 23872138
TI  - Failed acupuncture treatment of small intestinal obstruction after distal gastric
      cancer: a case report.

PMID- 23872139
TI  - Fenofibrate suppresses melanogenesis in B16-F10 melanoma cells via activation of
      the p38 mitogen-activated protein kinase pathway.
AB  - Fenofibrate and ciglitazone belong to the classes of fibrates and
      thiazolidinediones, respectively. Their pharmacological actions on peroxisome
      proliferator-activated receptors (PPARs) present a potential therapy for
      hyperlipidemia and hyperglycemia. However, the melanogenesis affected by PPAR
      ligands in melanocytes has not been well investigated. By determining the melanin
      content of cells treated with PPAR agonists, we showed that fenofibrate
      significantly reduced melanin synthesis, but its major active metabolite,
      fenofibric acid, did not. Notably, the suppression of melanogenesis by
      fenofibrate could not be prevented by the PPARalpha specific antagonist GW6471.
      In addition, T0901317, a liver X receptor (LXR) agonist, restored the
      antimelanogenic activity of fenofibrate. Accordingly, fenofibrate may suppress
      melanogenesis through a PPARalpha-independent pathway. Treatment of cells with
      fenofibrate led to the down-regulated gene expression of melanocortin 1 receptor
      (MC1R). Fenofibrate also attenuated the dihydroxyphenylalanine (DOPA)-staining
      activity and expression of tyrosinase as well as the expression of microphthalmia
      associated transcription factor (MITF). The phosphorylation of p38 mitogen
      activated protein kinase (MAPK) was stimulated by fenofibrate. Furthermore, the
      p38 MAPK inhibitor SB203580 prevented the repressive effects of fenofibrate on
      the melanin production. Taken together, the results of the present study suggest
      that fenofibrate inhibits melanin synthesis via the down-regulation of MC1R, the
      up-regulation of p38 MAPK, and interference with LXR signaling pathways to
      decrease the expression of tyrosinase in B16-F10 melanoma cells. 

PMID- 23872140
TI  - Ovarian expression and localization of a vitellogenin receptor with eight ligand
      binding repeats in the cutthroat trout (Oncorhynchus clarki).
AB  - A cDNA encoding a vitellogenin receptor with 8 ligand binding repeats (vtgr) was
      cloned from ovaries of the cutthroat trout, Oncorhynchus clarki. In situ
      hybridization and quantitative PCR analyses revealed that the main site of vtgr
      mRNA expression was the oocytes. Expression was strongly detected in perinucleous
      stage oocytes, gradually decreased as oocytes grew, and became hardly detectable
      in vitellogenic oocytes. A rabbit antibody (a-Vtgr) was raised against a
      recombinant Vtgr protein in order to immunologically detect and localize Vtgr
      within the ovarian follicles. Western blotting using a-Vtgr detected a bold band
      with an apparent mass of ~95-105kDa in an ovarian preparation that also bound
      Sakhalin taimen, Hucho perryi, vitellogenin in ligand blots. Immunohistochemistry
      using a-Vtgr revealed that the Vtgr was uniformly distributed throughout the
      ooplasm of perinucleolus stage oocytes, subsequently translocated to the
      periphery of lipid droplet stage oocytes, and became localized to the oolemma
      during vitellogenesis. We provide the first characterization of Vtgr at both the
      transcriptional and the translational levels in the cutthroat trout, and our
      results suggest that this receptor is involved in uptake of Vtg by oocytes of
      this species. 

PMID- 23872141
TI  - The role of the amygdala and the basal ganglia in visual processing of central
      vs. peripheral emotional content.
AB  - In human cognition, most relevant stimuli, such as faces, are processed in
      central vision. However, it is widely believed that recognition of relevant
      stimuli (e.g. threatening animal faces) at peripheral locations is also important
      due to their survival value. Moreover, task instructions have been shown to
      modulate brain regions involved in threat recognition (e.g. the amygdala). In
      this respect it is also controversial whether tasks requiring explicit focus on
      stimulus threat content vs. implicit processing differently engage primitive
      subcortical structures involved in emotional appraisal. Here we have addressed
      the role of central vs. peripheral processing in the human amygdala using animal
      threatening vs. non-threatening face stimuli. First, a simple animal face
      recognition task with threatening and non-threatening animal faces, as well as
      non-face control stimuli, was employed in naive subjects (implicit task). A
      subsequent task was then performed with the same stimulus categories (but
      different stimuli) in which subjects were told to explicitly detect threat
      signals. We found lateralized amygdala responses both to the spatial location of
      stimuli and to the threatening content of faces depending on the task performed:
      the right amygdala showed increased responses to central compared to left
      presented stimuli specifically during the threat detection task, while the left
      amygdala was better prone to discriminate threatening faces from non-facial
      displays during the animal face recognition task. Additionally, the right
      amygdala responded to faces during the threat detection task but only when
      centrally presented. Moreover, we have found no evidence for superior responses
      of the amygdala to peripheral stimuli. Importantly, we have found that striatal
      regions activate differentially depending on peripheral vs. central processing of
      threatening faces. Accordingly, peripheral processing of these stimuli activated
      more strongly the putaminal region, while central processing engaged mainly the
      caudate nucleus. We conclude that the human amygdala has a central bias for face
      stimuli, and that visual processing recruits different striatal regions,
      putaminal or caudate based, depending on the task and on whether peripheral or
      central visual processing is involved. 

PMID- 23872143
TI  - Solution structure and backbone dynamics of human Raf-1 kinase inhibitor protein.
AB  - Human Raf-1 kinase inhibitor protein (hRKIP) is a small multi-functional protein
      of 187 residues. It contains a conserved pocket, which binds a wide range of
      ligands from various small molecules to distinct proteins. To provide a
      structural basis for the ligand diversity of RKIP, we herein determined the
      solution structure of hRKIP, and analyzed its structural dynamics. In solution,
      hRKIP mainly comprises two antiparallel beta sheets, two alpha helices and two
      310 helices. NMR dynamic analysis reveals that the overall structure of hRKIP is
      rigid, but its C-terminal helix which is close to the ligand-binding site is
      mobile. In addition, residues around the ligand-binding pocket exhibit
      significant conformational exchange on the MUs-ms timescale. Conformational
      flexibility may allow the ligand-binding pocket and the C-terminal helix to adopt
      various conformations to interact with different substrates. This work may shed
      light on the underlying molecular mechanisms of how hRKIP recognizes and binds
      diverse substrate ligands.

PMID- 23872142
TI  - rhEGF-loaded PLGA-Alginate microspheres enhance the healing of full-thickness
      excisional wounds in diabetised Wistar rats.
AB  - Diabetic foot ulcers (DFUs) represent a major clinical challenge in the ageing
      population. To address this problem, rhEGF-loaded Poly-Lactic-co-Glycolic-Acid
      (PLGA)-Alginate microspheres (MS) were prepared by a modified w/o/w-double
      emulsion/solvent evaporation method. Different formulations were evaluated with
      the aim of optimising MSs properties by adding NaCl to the surfactant solution
      and/or the solvent removal phase and adding alginate as a second polymer. The
      characterisation of the developed MS showed that alginate incorporation increased
      the encapsulation efficiency (EE) and NaCl besides increasing the EE also became
      the particle surface smooth and regular. Once the MS were optimised, the target
      loading of rhEGF was increased to 1% (PLGA-Alginate MS), and particles were
      sterilised by gamma radiation to provide the correct dosage for in vivo studies.
      In vitro cell culture assays demonstrated that neither the microencapsulation nor
      the sterilisation process affected rhEGF bioactivity or rhEGF wound contraction.
      Finally, the MS were evaluated in vivo for treatment of the full-thickness wound
      model in diabetised Wistar rats. rhEGF MS treated animals showed a statistically
      significant decrease of the wound area by days 7 and 11, a complete re
      epithelisation by day 11 and an earlier resolution of the inflammatory process.
      Overall, these findings demonstrate the promising potential of rhEGF-loaded MS
      (PLGA-Alginate MS) to promote faster and more effective wound healing, and
      suggest its possible application in DFU treatment. 

PMID- 23872144
TI  - CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell
      lymphoma xenograft mouse models.
AB  - Adoptive T-cell therapy with CD19-specific chimeric antigen receptors (CARs) is
      promising for treatment of advanced B-cell malignancies. Tumor targeting of CAR
      modified T-cells is likely to contribute therapeutic potency; therefore we
      examined the relationship between the ability of CD19-specific CAR (CD19-CAR)
      transduced T-cells to accumulate at CD19(+) tumor lesions, and their ability to
      provide anti-tumor effects in xenograft mouse models. Normal human peripheral
      blood lymphocytes, activated with immobilized RetroNectin and anti-CD3
      antibodies, were transduced with retroviral vectors that encode CD19-CAR.
      Expanded CD19-CAR T-cells with a high transgene expression level of about 75%
      produced IL-2 and IFN-gamma in response to CD19, and lysed both Raji and Daudi
      CD19(+) human B-cell lymphoma cell lines. Furthermore, these cells efficiently
      accumulated at Raji tumor lesions where they suppressed tumor progression and
      prolonged survival in tumor-bearing Rag2(-/-)gammac(-/-) immunodeficient mice
      compared to control cohorts. These results show that the ability of CD19-CAR T
      cells to home in on tumor lesions is pivotal for their anti-tumor effects in our
      xenograft models, and therefore may enhance the efficacy of adoptive T-cell
      therapy for refractory B-cell lymphoma. 

PMID- 23872145
TI  - Intestinal absorption of lysozyme, an egg-white allergen, in rats: kinetics and
      effect of NSAIDs.
AB  - The absorption pathway(s) of a representative food allergen, lysozyme, and the
      mechanisms of lysozyme absorption facilitated by non-steroidal anti-inflammatory
      drugs were examined by intestinal closed-loop and re-circulating perfusion
      methods in rats. The absorption rate of fluorescein isothiocyanate (FITC)-labeled
      lysozyme in the proximal intestine was higher than that for a marker of non
      specific absorption, FD-10, and was suppressed by colchicine (endocytosis
      inhibitor). Aspirin increased the absorption of FITC-lysozyme in the proximal
      intestine with no effects on tissue accumulation. Diclofenac facilitated FITC
      lysozyme absorption, but meloxicam and loxoprofen exerted no effects on
      absorption. Co-administration of misoprostol (synthetic prostaglandin-E1 analog)
      with aspirin significantly ameliorated the aspirin-facilitated absorption of FITC
      lysozyme to the same level as that seen with controls. Thus, lysozyme absorption
      was mediated by endocytic and paracellular pathways in the proximal intestine,
      and was facilitated by aspirin and diclofenac after impairment of the
      paracellular pathway. Misoprostol may suppress the allergen absorption
      facilitated by aspirin. 

PMID- 23872146
TI  - CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of
      macrophage polarization in adipose tissues.
AB  - It has been established that obesity alters the metabolic and endocrine function
      of adipose tissue and, together with accumulation of adipose tissue macrophages,
      contributes to insulin resistance. Although numerous studies have reported that
      shifting the polarization of macrophages from M1 to M2 can alleviate adipose
      tissue inflammation, manipulation of macrophage polarization has not been
      considered as a specific therapy. Here, we determined whether cytotoxic T
      lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance
      by induction of macrophages from proinflammatory M1 to anti-inflammatory M2
      polarization in the adipose tissues of high fat diet-induced insulin-resistant
      mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression
      to M2 polarization, which increased the levels of arginase 1. Furthermore, flow
      cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to
      CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight
      reductions of epididymal and subcutaneous adipose tissues, which may be closely
      related to overexpression of apoptosis inhibitors in macrophages. Moreover,
      proinflammatory cytokine and chemokine levels decreased significantly. In
      contrast, CCAAT enhancer binding protein alpha, peroxisome proliferator-activated
      receptor gamma, and adiponectin expression increased significantly in
      subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may
      lead to an ideal anti-obesity/inflammation/insulin resistance agent. 

PMID- 23872147
TI  - p130Cas controls the susceptibility of cancer cells to TGF-beta-induced growth
      inhibition.
AB  - Transforming growth factor-beta (TGF-beta) suppresses the initiation of
      tumorigenesis by causing arrest at the G1 phase of the cell cycle. The loss of
      the antiproliferative function of TGF-beta is a hallmark of many cancers. Here we
      report that p130Cas plays a role in determining the cellular responsiveness to
      TGF-beta-induced growth inhibition in some cancer cells. An analysis of the
      tyrosine phosphorylation levels of p130Cas revealed higher levels of
      phosphorylation in cancer cell lines (MCF7 and A375) than in corresponding normal
      cell lines (MCF10A and MEL-STV). In contrast to normal cells, the cancer cells
      showed resistance to not only TGF-beta-induced Smad3 phosphorylation and p21
      expression, but also growth inhibition. However, silencing p130Cas using siRNA
      was sufficient to restore Smad3 phosphorylation and p21 expression, as well as
      the susceptibility to TGF-beta-induced growth inhibition. Interestingly, the
      stable overexpression of p130Cas accelerated TGF-beta-induced epithelial
      mesenchymal transition. Our results suggest that elevated expression and tyrosine
      phosphorylation of p130Cas contributes to the resistance to TGF-beta-induced
      growth inhibition, and thus to the initiation and progression of human cancers
      that harbor an active integrin signal. 

PMID- 23872148
TI  - Hypoxia mediated expression of stem cell markers in VHL-associated
      hemangioblastomas.
AB  - Hemangioblastomas of the retina, central nervous system, and kidney are observed
      in patients with mutations in the von Hippel-Lindau (VHL) tumor suppressor gene.
      Mutations in the VHL lead to constitutive activation of hypoxia-inducible-factor
      (HIF) pathway. HIF-mediated expression of pro-angiogenic genes causes extensive
      pathological neovascularization in hemangioblastomas. A number of studies have
      shown coexistence of pro-angiogenic and stem cell markers in 'tumorlet-like
      stromal cells' in the retinal and optic nerve hemangioblastomas, leading to
      suggestions that hemangioblastomas originate from developmentally arrested stem
      cells or embryonic progenitors. Since recent studies have shown that the HIF
      pathway also plays a role in the maintenance/de-differentiation of normal and
      cancerous stem cells, we evaluated the role of the HIF pathway in the expression
      of stem cell markers in VHL-/- renal cell carcinoma cells under normoxia or
      VHL+/+ retinal pigment epithelial cells under hypoxia. Here we show that the
      expression of stem cell markers in hemangioblastomas is due to activation of the
      HIF pathway. Further, we show that honokiol, digoxin, and doxorubicin, three
      recently identified HIF inhibitors from natural sources, blocks the expression of
      stem cell markers. Our results show the mechanism for the cytological origin of
      neoplastic stromal cells in hemangioblastomas, and suggest that inhibition of the
      HIF pathway is an attractive strategy for the treatment of hemangioblastomas. 

PMID- 23872149
TI  - Internalisation and multiple phosphorylation of gamma-Conglutin, the lupin seed
      glycaemia-lowering protein, in HepG2 cells.
AB  - Lupin seed gamma-Conglutin is a protein capable of reducing glycaemia in
      mammalians and increasing glucose uptake by model cells. This work investigated
      whether gamma-Conglutin is internalised into the target cells and undergoes any
      covalent change during the process, as a first step to understanding its
      mechanism of action. To this purpose, gamma-Conglutin-treated and untreated HepG2
      cells were submitted to confocal and transmission electron microscopy. Immune
      revelation of gamma-Conglutin at various intervals revealed its accumulation
      inside the cytosol. In parallel, 2D-electrophoresis of the cell lysates and
      antibody reaction of the blotted maps showed the presence of the protein intact
      subunits inside the treated cells, whilest no trace of the protein was found in
      the control cells. However, gamma-Conglutin-related spots with an unexpectedly
      low pI were also observed in the maps. These spots were excised, trypsin-treated
      and submitted to MS/MS spectrometric analysis. The presence of phosphorylated
      amino acids was detected. These findings, by showing that gamma-Conglutin is
      internalised by HepG2 cells in an intact form and is modified by multiple
      phosphorylation, open the way to the understanding of the lupin gamma-Conglutin
      insulin-mimetic activity.

PMID- 23872150
TI  - Estrogen modulates plasminogen promoter activity.
AB  - Postmenopausal women treated with estrogen hormone replacement therapy and female
      patients with hypoplasminogenemia receiving oral contraceptives show increasing
      plasminogen (PLG) concentrations. The elevated PLG levels are in contrast to the
      estrogen dependent decline of lipoptrotein(a) [Lp(a)], whose main protein
      component apolipoprotein(a) [APO(a)] is highly homologous to PLG in protein and
      gene structure and is also located in its immediate vicinity on chromosome 6q26.
      The intergenic region between both genes comprises several transcription
      regulatory regions with enhancer sequences that increase the basal activity of
      the PLG core promoter. Using luciferase reporter assays we demonstrate that the
      minimal PLG promoter is insensitive to estrogen. However, an estrogen response
      element located 11.5 kb upstream of the PLG transcription start site is able to
      convey a dramatic estrogen-dependent elevation of PLG-minimal promoter driven
      reporter gene expression. In contrast, the activating effect of two additional
      enhancer elements, among them an DNase I hypersensitivity region that has been
      shown to regulate the APO(a) minimal promoter activity, is abrogated by estrogen.
      Thus, the identified estrogen-responsive elements provide a gene and tissue
      specific framework by which PLG expression is regulated and whose activity is
      orchestrated by yet unknown accessory factors.

PMID- 23872151
TI  - MicroRNA-340 suppresses osteosarcoma tumor growth and metastasis by directly
      targeting ROCK1.
AB  - MicroRNAs (miRNAs) play key roles in cancer development and progression. In the
      present study, we investigated the role of miR-340 in the progression and
      metastasis of osteosarcoma (OS). Our results showed that miR-340 was frequently
      downregulated in OS tumors and cell lines. Overexpression of miR-340 in OS cell
      lines significantly inhibited cell proliferation, migration, and invasion in
      vitro, and tumor growth and metastasis in a xenograft mouse model. ROCK1 was
      identified as a target of miR-340, and ectopic expression of miR-340
      downregulated ROCK1 by direct binding to its 3' untranslated region. siRNA
      mediated silencing of ROCK1 phenocopied the effects of miR-340 overexpression,
      whereas restoration of ROCK1 in miR-340-overexpressing OS cells reversed the
      suppressive effects of miR-340. Together, these findings indicate that miR-340
      acts as a tumor suppressor and its downregulation in tumor tissues may contribute
      to the progression and metastasis of OS through a mechanism involving ROCK1,
      suggesting miR-340 as a potential new diagnostic and therapeutic target for the
      treatment of OS.

PMID- 23872152
TI  - Synergistic effect of the L-tryptophan and kynurenic acid with dipyrone or
      paracetamol in mice.
AB  - PURPOSE: Our great interest in this work was study the synergism between l
      tryptophan and dipyrone or paracetamol as well as the interaction of kynurenic
      acid (l-tryptophan metabolite) and these analgesics agents utilizing a robust
      methodology. METHODS: We performed the writhing test induced by acetic acid in
      mice to evaluate the antinociceptive effect of the treatments isolated and
      combined (p.o. and i.p.). Dose-response curves were constructed and the values of
      ED50 for treatment alone and combined were statistically compared. In addition,
      isobolographic analysis was performed and the experimental values were compared
      with the theoretical values for simple additive effect. RESULTS: The combined
      treatment with l-tryptophan and dipyrone or paracetamol reduced significantly the
      ED50 of these analgesics when compared to the isolated treatments. l-tryptophan
      alone has no antinociceptive effect. l-Tryptophan increases the central amount of
      5-HT and the synergism with dipyrone is antagonized by the 5-HT depletion. The
      kyna has an antinociceptive dose-related effect and a synergistic interaction
      with dipyrone and paracetamol verified by isobolographic analyses and confirmed
      by experimental values of ED50 of combined treatments were statistically lower
      than theoretical calculated values for simple additive effect. Melatonin
      antagonist receptor attenuates the antinociceptive synergism between l-tryptophan
      and dipyrone. CONCLUSION: Our results demonstrate that the increased 5-HT amount
      on the central nervous system is not per se capable to induce antinociception.
      The l-tryptophan interacts synergistically with dipyrone and paracetamol both
      orally and by i.p. route. This effect is dependent on the biotransformation of l
      tryptophan to 5-HT and involves kynurenic acid and melatonin receptors.

PMID- 23872153
TI  - When size does matter: organelle size influences the properties of transport
      mediated by molecular motors.
AB  - BACKGROUND: Organelle transport is driven by the action of molecular motors. In
      this work, we studied the dynamics of organelles of different sizes with the aim
      of understanding the complex relation between organelle motion and
      microenvironment. METHODS: We used single particle tracking to obtain
      trajectories of melanosomes (pigmented organelles in Xenopus laevis
      melanophores). In response to certain hormones, melanosomes disperse in the
      cytoplasm or aggregate in the perinuclear region by the combined action of
      microtubule and actin motors. RESULTS AND CONCLUSIONS: Melanosome trajectories
      followed an anomalous diffusion model in which the anomalous diffusion exponent
      (alpha) provided information regarding the trajectories' topography and thus of
      the processes causing it. During aggregation, the directionality of big
      organelles was higher than that of small organelles and did not depend on the
      presence of either actin or intermediate filaments (IF). Depolymerization of IF
      significantly reduced alpha values of small organelles during aggregation but
      slightly affect their directionality during dispersion. GENERAL SIGNIFICANCE: Our
      results could be interpreted considering that the number of copies of active
      motors increases with organelle size. Transport of big organelles was not
      influenced by actin or IF during aggregation showing that these organelles are
      moved processively by the collective action of dynein motors. Also, we found that
      intermediate filaments enhance the directionality of small organelles suggesting
      that this network keeps organelles close to the tracks allowing their efficient
      reattachment. The higher directionality of small organelles during dispersion
      could be explained considering the better performance of kinesin-2 vs. dynein at
      the single molecule level.

PMID- 23872154
TI  - Metacognitive awareness of covert somatosensory attention corresponds to
      contralateral alpha power.
AB  - Studies on metacognition have shown that participants can report on their
      performance on a wide range of perceptual, memory and behavioral tasks. We know
      little, however, about the ability to report on one's attentional focus. The
      degree and direction of somatosensory attention can, however, be readily
      discerned through suppression of alpha band frequencies in EEG/MEG produced by
      the somatosensory cortex. Such top-down attentional modulations of cortical
      excitability have been shown to result in better discrimination performance and
      decreased response times. In this study we asked whether the degree of
      attentional focus is also accessible for subjective report, and whether such
      evaluations correspond to the amount of somatosensory alpha activity. In response
      to auditory cues participants maintained somatosensory attention to either their
      left or right hand for intervals varying randomly between 5 and 32 seconds, while
      their brain activity was recorded with MEG. Trials were terminated by a probe
      sound, to which they reported their level of attention on the cued hand right
      before probe-onset. Using a beamformer approach, we quantified the alpha activity
      in left and right somatosensory regions, one second before the probe. Alpha
      activity from contra- and ipsilateral somatosensory cortices for high versus low
      attention trials were compared. As predicted, the contralateral somatosensory
      alpha depression correlated with higher reported attentional focus. Finally,
      alpha activity two to three seconds before the probe-onset was correlated with
      attentional focus. We conclude that somatosensory attention is indeed accessible
      to metacognitive awareness.

PMID- 23872155
TI  - Overlapping and parallel cerebello-cerebral networks contributing to sensorimotor
      control: an intrinsic functional connectivity study.
AB  - In concert with sensorimotor control areas of the cerebrum, the cerebellum shows
      differential activation patterns during a variety of sensorimotor-related tasks.
      However, the spatial details and extent of the complex and heterogeneous
      cerebello-cerebral systems involved in action control remain uncertain. In this
      study, we use intrinsic functional connectivity (iFC) to examine cerebello
      cerebral networks of five cerebellar lobules (I-IV, V, VI, and VIIIa/b) that have
      been empirically identified to form the functional basis of sensorimotor
      processes. A refined cerebellar seed-region selection allowed us to identify a
      network of primary sensorimotor and supplementary motor areas (I-V), a network of
      prefrontal, premotor, occipito-temporal and inferior-parietal regions (VI), and
      two largely overlapping networks involving premotor and superior parietal
      regions, the temporo-parietal junction as well as occipito-temporal regions
      (VIIIa/b). All networks involved the medial prefrontal/cingulate cortex. These
      cerebral clusters were used in a partial correlation analysis to systematically
      map cerebral connectivity throughout the entire cerebellum. We discuss these
      findings in the framework of affective and cognitive control, sensorimotor,
      multisensory systems, and executive/language systems. Within the cerebellum we
      found that cerebro-cerebellar systems seem to run in parallel, as indicated by
      distinct sublobular functional topography of prefrontal, parietal, sensorimotor,
      cingulate, and occipito-temporal regions. However, all areas showed overlapping
      connectivity to various degrees in both hemispheres. The results of both analyses
      demonstrate that different sublobular parts of the cerebellar lobules may
      dominate in different aspects of primary or higher-order sensorimotor processing.
      This systems-level cerebellar organization provides a more detailed structure for
      cerebello-cerebral interaction which contributes to our understanding of complex
      motor behavior. 

PMID- 23872156
TI  - Spatial encoding and underlying circuitry in scene-selective cortex.
AB  - Three cortical areas (Retro-Splenial Cortex (RSC), Transverse Occipital Sulcus
      (TOS) and Parahippocampal Place Area (PPA)) respond selectively to scenes.
      However, their wider role in spatial encoding and their functional connectivity
      remain unclear. Using fMRI, first we tested the responses of these areas during
      spatial comparison tasks using dot targets on white noise. Activity increased
      during task performance in both RSC and TOS, but not in PPA. However, the
      amplitude of task-driven activity and behavioral measures of task demand were
      correlated only in RSC. A control experiment showed that none of these areas were
      activated during a comparable shape comparison task. Secondly, we analyzed
      functional connectivity of these areas during the resting state. Results revealed
      a significant connection between RSC and frontal association areas (known to be
      involved in perceptual decision-making). In contrast, TOS showed functional
      connections dorsally with the Inferior Parietal Sulcus, and ventrally with the
      Lateral Occipital Complex--but not with RSC and/or frontal association areas.
      Moreover, RSC and TOS showed differentiable functional connections with the
      anterior-medial and posterior-lateral parts of PPA, respectively. These results
      suggest two parallel pathways for spatial encoding, including RSC and TOS
      respectively. Only the RSC network was involved in active spatial comparisons.

PMID- 23872157
TI  - Molecular concentration of deoxyHb in human prefrontal cortex predicts the
      emergence and suppression of consciousness.
AB  - This is the first study to use fNIRS to explore anaesthetic depth and awakening
      during surgery with general anaesthesia. A 16 channel continuous wave (CW)
      functional near-infrared system (fNIRS) was used to monitor PFC activity. These
      outcomes were compared to BIS measures. The results indicate that deoxyHb
      concentration in the PFC varies during the suppression and emergence of
      consciousness. During suppression, deoxyHb levels increase, signalling the
      deactivation of the PFC, while during emergence, deoxyHb concentration drops,
      initiating PFC activation and the recovery of consciousness. Furthermore, BIS and
      deoxyHb concentrations in the PFC display a high negative correlation throughout
      the different anaesthetic phases. These findings suggest that deoxyHb could be a
      reliable marker for monitoring anaesthetic depth, and that the PFC intervenes in
      the suppression and emergence of consciousness. 

PMID- 23872159
TI  - Evaluation of motorcycle safety strategies using the severity of injuries.
AB  - The growth of motorcycle fatalities in California has been especially prominent,
      specifically with regard to the 24 and under age group and those aged 45-54. This
      research quantitatively examined factors associated with motorcyclist fatalities
      and assessed strategies that could improve motorcyclist safety, specifically
      focusing on the two age groups mentioned above. Severity of injury was estimated
      separately for both age groups with multinomial logit models and pseudo
      elasticity using motorcycle-related collision data that was collected between
      2005 and 2009. The results were compared with motorcyclists aged 35-44, a group
      that shows a consistent trend of fatalities. This research found that lack or
      improper use of helmets, victim ejection, alcohol/drug effects, collisions (head
      on, broadside, hit-object), and truck involvement were more likely to result in
      fatal injuries regardless of age group. Weekend and non-peak hour activity was
      found to have a strong effect in both the younger and older age groups. Two
      factors, movement of running off the road preceding a collision and multi-vehicle
      involvement, were found to be statistically significant factors in increasing
      older motorcyclist fatalities. Use of street lights in the dark was found to
      decrease the probability of severe injury for older motorcyclists. Driver type of
      victim, at-fault driver, local road, and speed violation were significant factors
      in increasing the fatalities of younger motorcyclists. Road conditions and
      collision location factors were not found to be statistically significant to
      motorcyclist fatalities. Based on the statistically significant factors
      identified in this research, the following safety strategies appear to be
      effective methods of reducing motorcyclist fatalities: public education of
      alcohol use, promoting helmet use, enforcing heavy vehicle and speed violations,
      improving roadway facilities, clearer roadway guidance and street lighting
      systems, and motorcyclist training. 

PMID- 23872158
TI  - Interleaved imaging of cerebral hemodynamics and blood flow index to monitor
      ischemic stroke and treatment in rat by volumetric diffuse optical tomography.
AB  - Diffuse optical tomography (DOT) has been used by several groups to assess
      cerebral hemodynamics of cerebral ischemia in humans and animals. In this study,
      we combined DOT with an indocyanine green (ICG)-tracking method to achieve
      interleaved images of cerebral hemodynamics and blood flow index (BFI) using two
      middle cerebral artery occlusion (MCAO) rat models. To achieve volumetric images
      with high-spatial resolution, we first integrated a depth compensation algorithm
      (DCA) with a volumetric mesh-based rat head model to generate three-dimensional
      (3D) DOT on a rat brain atlas. Then, the experimental DOT data from two rat
      models were collected using interleaved strategy for cerebral hemodynamics and
      BFI during and after ischemic stroke, with and without a thrombolytic therapy for
      the embolic MCAO model. The acquired animal data were further analyzed using the
      integrated rat-atlas-guided DOT method to form time-evolving 3D images of both
      cerebral hemodynamics and BFI. In particular, we were able to show and identify
      therapeutic outcomes of a thrombolytic treatment applied to the embolism-induced
      ischemic model. This paper demonstrates that volumetric DOT is capable of
      providing high-quality, interleaved images of cerebral hemodynamics and blood
      perfusion in small animals during and after ischemic stroke, with excellent 3D
      visualization and quantifications. 

PMID- 23872160
TI  - Highly sensitive HPLC method for assay of aliskiren in human plasma through
      derivatization with 1-naphthyl isocyanate using UV detection.
AB  - A simple and sensitive HPLC method has been developed for the determination of
      aliskiren in human plasma through derivatization with 1-naphthyl isocyanate. The
      separation was achieved on a C18 column using a mobile phase consisting of
      acetonitrile/water/phosphoric acid (45:55:0.01, v/v/v, pH 3.2) in a flow rate of
      1mL/min with UV detection at 230nm. Caffeine was used as an internal standard.
      The factors influencing the derivatization reaction yields were carefully studied
      and optimized. The method was linear over the concentration range of 5-400ng/mL
      with a detection limit of 0.5ng/mL and a limit of quantification of 1.0ng/mL. The
      relative standard deviation was less than 4.2% for both intra-day assay and inter
      day assay results. No interferences from endogenous compounds were encountered.
      The percentage recovery was in the range 97.1-98.6%. The method is suitable for
      routine therapeutic drug monitoring and for pharmacokinetic studies. 

PMID- 23872161
TI  - Development and validation of a sensitive LC-MS/MS method for the determination
      of fenoterol in human plasma and urine samples.
AB  - Due to the lack of sensitivity in current methods for the determination of
      fenoterol (Fen), a rapid LC-MS/MS method was developed for the determination of
      (R,R')-Fen and (R,R';S,S')-Fen in plasma and urine. The method was fully
      validated and was linear from 50pg/ml to 2000pg/ml for plasma and from 2.500ng/ml
      to 160ng/ml for urine with a lower limit of quantitation of 52.8pg/ml in plasma.
      The coefficient of variation was <15% for the high QC standards and <10% for the
      low QC standards in plasma and was <15% for the high and low QC standards in
      urine. The relative concentrations of (R,R')-Fen and (S,S')-Fen were determined
      using a chirobiotic T chiral stationary phase. The method was used to determine
      the concentration of (R,R')-Fen in plasma and urine samples obtained in an oral
      cross-over study of (R,R')-Fen and (R,R';S,S')-Fen formulations. The results
      demonstrated a potential pre-systemic enantioselective interaction in which the
      (S,S')-Fen reduces the sulfation of the active (R,R')-Fen. The data suggest that
      a non-racemic mixture of the Fen enantiomers may provide better bioavailability
      of the active (R,R')-Fen for use in the treatment of cardiovascular disease. 

PMID- 23872162
TI  - Experiences in a family with the Upshaw-Schulman syndrome over a 44-year period.
AB  - A family with a novel c.717_del frameshift and a c.3655C > T missense mutation of
      a disintegrin and metalloproteinase with thrombospondin type I motif, member 13
      protein (ADAMTS13) is described. Family members have been under observation for
      44 years. Two double heterozygotes have severe early-onset Upshaw-Schulman
      syndrome and require prophylactic plasma infusions. Analysis reveals that 2
      weekly plasma infusions are not sufficient in preventing laboratory evidence of a
      thrombotic thrombocytopenic purpura (TTP) attack. Both the double heterozygotes
      also have a heterozygous factor V Leiden G1291A mutation. One underwent
      splenectomy, which did not reduce the frequency of TTP episodes but resulted in a
      recurrent pulmonary embolism and has necessitated lifelong anticoagulant therapy.
      The other has mild chronic renal failure and has had episodes of atrial
      fibrillation and cerebral infarction. Of the 3 heterozygotes in the family, 1 has
      had episodes of mild thrombocytopenia. 

PMID- 23872163
TI  - Impact of the neutrophil-to-lymphocyte ratio in patients with coronary artery
      disease.

PMID- 23872164
TI  - Not everyone's heart contracts to reward: Insensitivity to varying levels of
      reward in dysphoria.
AB  - Reward insensitivity in depression and dysphoria has been demonstrated by self
      report, behavioral, and neuroscience data. These findings show less anticipated
      and experienced pleasure to rewarding stimuli, no behavioral adaptation in
      anticipation of rewards, and altered functioning in reward-related brain areas.
      The present study expands previous research by using cardiovascular reactivity to
      three levels of reward as an indicator of effort mobilization. Undergraduates
      with low versus high depression scores worked on a cognitive task in anticipation
      of no, versus a small, versus a significant amount of money for successful task
      performance. Results of pre-ejection period and heart rate reactivity confirmed
      the expected linear increase as a function of reward value in nondysphoric
      participants and the expected blunted response across all reward levels in
      dysphoric participants. The present findings thus show that dysphoric individuals
      have a motivational deficit in terms of reduced effort-related cardiac reactivity
      when anticipating a monetary reward. 

PMID- 23872165
TI  - Two-year stability of the late positive potential across middle childhood and
      adolescence.
AB  - The late positive potential (LPP) may be a useful measure of individual
      differences in emotional processing across development, but little is known about
      the stability of the LPP across time. We assessed the LPP and behavioral measures
      of emotional interference following pleasant, unpleasant, and neutral images in 8
      to 13-year-old youth. Approximately two years later, the same participants
      completed the task again (N=34). Results indicated that the LPP is moderately-to
      highly reliable across development. Stability was lower and more inconsistent for
      behavioral measures. In addition, consistent with previous cross-sectional
      analyses, a decrease in occipital activity was observed at the second assessment.
      Results indicate that the LPP appears to be a stable measure of emotional
      processing, even across a fairly large period of development. 

PMID- 23872166
TI  - The flash grab effect.
AB  - When an object moves back and forth, its trajectory appears significantly shorter
      than it actually is. The object appears to stop and reverse well before its
      actual reversal point, as if there is some averaging of location within a window
      of about 100 ms (Sinico et al., 2009). Surprisingly, if a bar is flashed at the
      physical end point of the trajectory, right on top of the object, just as it
      reverses direction, the flash is also shifted - grabbed by the object - and is
      seen at the perceived endpoint of the trajectory rather than the physical
      endpoint. This can shift the perceived location of the flash by as much as 2 or 3
      times its physical size and by up to several degrees of visual angle. We first
      show that the position shift of the flash is generated by the trajectory
      shortening, as the same shift is seen with or without the flash. The flash itself
      is only grabbed if it is presented within a small spatiotemporal attraction zone
      around the physical end point of the trajectory. Any flash falling in that zone
      is pulled toward the perceived endpoint. The effect scales linearly with speed,
      up to a maximum, and is independent of the contrast of the moving stimulus once
      it is above 5%. Finally, we demonstrate that this position shift requires
      attention. These results reveal a new "flash grab" effect in the family of motion
      induced position shifts. Although it most resembles the flash drag effect, it
      differs from this in the following ways: (1) it has a different temporal profile,
      (2) it requires attention, (3) it is about 10 times larger.

PMID- 23872167
TI  - Spontaneous recovery of motion and face aftereffects.
AB  - The ability of the visual system to rapidly adjust to changing environmental
      conditions is one of its key characteristics. Environmental changes can occur
      over a variety of timescales, however, and it remains unknown how the visual
      system adapts to these. Does a single mechanism control adaptation across all
      timescales, or is adaptation subserved by multiple mechanisms, each of which is
      tuned to its preferred duration? To address this question, we conducted three
      experiments in which subjects viewed motion (Exp. 1 and 2) or faces (Exp. 3) in a
      sequence designed to produce opposing aftereffects. A first adapter was presented
      for a relatively long duration, while a second one was presented only long enough
      to extinguish the effects of the initial adapter. Continued measurement of
      aftereffects revealed a spontaneous recovery of adaptation caused by the initial,
      longer-lasting adapter in all three experiments. This pattern of results suggests
      that adaptation in the visual system generally reflects a combination of multiple
      temporally-tuned mechanisms. 

PMID- 23872168
TI  - Mutational analysis of the antizyme-binding element reveals critical residues for
      the function of ornithine decarboxylase.
AB  - BACKGROUND: Ornithine decarboxylase (ODC), the key enzyme in the polyamine
      biosynthetic pathway, is highly regulated by antizymes (AZs), small proteins that
      bind and inhibit ODC and increase its proteasomal degradation. Early studies
      delimited the putative AZ-binding element (AZBE) to the region 117-140 of ODC.
      The aim of the present work was to study the importance of certain residues of
      the region 110-142 that includes the AZBE region for the interaction between ODC
      and AZ1 and the ODC functionality. METHODS: Computational analysis of the protein
      sequences of the extended AZBE site of ODC and ODC paralogues from different
      eukaryotes was used to search for conserved residues. The influence of these
      residues on ODC functionality was studied by site directed mutagenesis, followed
      by different biochemical techniques. RESULTS: The results revealed that: a) there
      are five conserved residues in ODC and its paralogues: K115, A123, E138, L139 and
      K141; b) among these, L139 is the most critical one for the interaction with AZs,
      since its substitution decreases the affinity of the mutant protein towards AZs;
      c) all these conserved residues, with the exception of A123, are critical for ODC
      activity; d) substitutions of K115, E138 or L139 diminish the formation of ODC
      homodimers. CONCLUSIONS: These results reveal that four of the invariant residues
      of the AZBE region are strongly related to ODC functionality. GENERAL
      SIGNIFICANCE: This work helps to understand the interaction between ODC and AZ1,
      and describes various new residues involved in ODC activity, a key enzyme for
      cell growth and proliferation.

PMID- 23872169
TI  - Dolastatin, along with Celecoxib, stimulates apoptosis by a mechanism involving
      oxidative stress, membrane potential change and PI3-K/AKT pathway down
      regulation.
AB  - BACKGROUND: Phosphoinositide 3-kinase (PI3-K) is an important regulator of
      oncogenesis and apoptosis in various types of cancers including colon cancer. A
      combinatorial strategy of using Cyclooxygenase-2 inhibitor, Celecoxib and
      Dolastatin, a linear peptide from marine mollusks of Indian Ocean origin has
      shown anti-neoplastic effects in colon cancer in a rat model. METHODS: The signal
      transduction pathway of PI3-K/AKT and the downstream signaling proteins had been
      studied in an early stage of colon carcinogenesis (DMH induced) by gene and
      protein expression, apoptotic studies by colonocyte apoptotic bleb assay,
      intracellular calcium level by fluorescence spectrometry, mitochondrial membrane
      potential by Rhodamine 123 flow cytometry and Reactive oxygen species
      measurement. Molecular docking analysis was employed to study the interaction of
      oncogenic proteins and the ligand, Celecoxib and Dolastatin. RESULTS: Apoptotic
      cell index was lowered with DMH while both the drugs increased it and inhibited
      PI3-K and AKT expression. Docking studies revealed both the proteins targeted by
      the drugs via an ATP binding site. An increased expression of GSK-3beta, pro
      apoptotic protein Bad, transcription factor Egr-1, tumor suppressor protein PTEN
      while a downregulation of G1-associated cell cycle protein, Cyclin D1 and
      increased intracellular calcium as well as reactive oxygen species were observed.
      Also, the number of cells having a higher mitochondrial membrane potential was
      lowered. CONCLUSION: Celecoxib and Dolastatin inhibited the tumor development
      through regulation of the PI3-K/AKT pathway which can act as a novel target for
      these drugs. GENERAL SIGNIFICANCE: The anti-cancer properties of Dolastatin, a
      peptide isolated from marine mollusks in colorectal cancer is shown.

PMID- 23872170
TI  - Caffeine monitoring in biological fluids by solid surface fluorescence using
      membranes modified with nanotubes.
AB  - BACKGROUND: In this work, a new methodology based upon enhancement of rhodamine B
      fluorescent signal is proposed for the quantification of caffeine traces.
      METHODS: Membrane filters treated with multiple wall carbon nanotubes were
      employed as solid support for determination step by solid surface fluorescence.
      RESULTS: Experimental variables that influence the preconcentration step and
      fluorimetric sensitivity have been optimized using uni-variation assays,
      presenting linearity from 1.1 to 9.7*10(3) MUg/l, with a correlation coefficient
      of 0.99. At optimal conditions, a limit of detection of 0.3 MUg/l and a limit of
      quantification of 1.1 MUg/l were obtained. The method showed good sensitivity and
      adequate selectivity and was satisfactorily applied to the determination of trace
      amounts of caffeine in urine, plasma and serum belonging to subjects with
      different sex, ages and habit of caffeine intake. CONCLUSIONS: Chemofiltration
      step eliminated the highly fluorescent matrix, thus enabling and allowing CF
      quantification, in the presence of other methylxanthines. The proposed
      methodology represents an innovative application of the solid surface
      fluorescence using membrane filters modified with MWCNTs.

PMID- 23872171
TI  - C3435T polymorphism of MDR1 gene with warfarin resistance.
AB  - BACKGROUND: Some patients show warfarin resistance needing more than 70 mg of
      warfarin per week. In this study, we examined if C3435T polymorphism of MDR1 gene
      could be a factor of warfarin resistance. METHODS: We examined 196 blood
      specimens from the patients who took warfarin more than 42 mg/week for at least 1
      year. The subjects consisted of 74 European Americans, 59 African Americans, 42
      Hispanic Americans and 21 Asian Americans. Genotype of C3435T polymorphism was
      determined by using real-time polymerase chain reaction (PCR). RESULTS: Ninety
      (45.9%) of the 196 patients had C3435T genotype and the remaining patients had
      C3435C genotype (35.7%) and T3435T genotype (18.4%). Mean dose of warfarin of
      patients with C3435C, C3435T and T3435T genotypes were 59.5mg/week, 56.9 mg/week
      and 55.6 mg/week, respectively. There was no statistical difference in the dose
      of warfarin between the 3 genotypes within each race. CONCLUSION: Our results
      suggest that C3435T polymorphism of MDR1 gene is not associated with warfarin
      resistance.

PMID- 23872172
TI  - Patient-reported recall of smoking cessation interventions from a health
      professional.
AB  - OBJECTIVE: To determine the prevalence and characteristics of current cigarette
      smokers who report receiving health care provider interventions ('5A's': ask,
      advise, assess, assist, arrange) for smoking cessation. METHODS: Data came from
      the 2009-2010 National Adult Tobacco Survey, a telephone survey of United States
      adults aged >= 18 years. Among current cigarette smokers who reported visiting a
      health professional in the past year (n=16,542), estimates were calculated
      overall and by sex, age, race/ethnicity, education, income, health insurance
      coverage, and sexual orientation. RESULTS: Among smokers who visited a health
      professional (75.2%), 87.9% were asked if they used tobacco, 65.8% were advised
      to quit, and 42.6% were asked if they wanted to quit. Among those wanting to
      quit, 78.2% were offered assistance and 17.5% had follow-up arranged. Receipt of
      the 'ask' component was lower among males and uninsured individuals. Receipt of
      the 'advise' and 'assess' components was lower among those aged 18-24 and
      uninsured individuals. Receipt of the 'assist' component was lower among non
      Hispanic blacks. No differences were observed for the 'arrange' component.
      CONCLUSIONS: Many current smokers report receiving health care provider
      interventions for smoking cessation. Continued efforts to educate, encourage, and
      support all health professionals to provide effective, comprehensive tobacco
      cessation interventions to their patients may be beneficial.

PMID- 23872173
TI  - Using agent-based models to inform evaluation of complex interventions: examples
      from the built environment.

PMID- 23872174
TI  - Risk factors for single and recurrent falls: a prospective study of falls in
      community dwelling seniors without cognitive impairment.
AB  - OBJECTIVE: The purpose of this study is to contribute evidence towards
      heterogeneity in risk factors for single and recurrent falls. METHOD: This is a
      prospective study conducted in Taiwan. Participants were randomly selected from
      the examinees of the annual health examination in 2010. Participants were
      interviewed with a detailed questionnaire and followed up one year later.
      Predictor variables included socio-demographic characteristics, medical
      conditions, laboratory data, and risk factors for osteoporosis. The outcome was
      falls in the ensuing 12 months. RESULTS: The mean age of the 653 completers was
      75.6 +/- 6.4. Half (48.7%) were women. Fallers and recurrent fallers comprised
      14.5% and 6.0% of the participants, respectively. Blurred vision (adjusted odds
      ratio (aOR): 1.93, 95% confidence interval (CI): 1.02-3.67), minimal outdoor
      activities (aOR: 2.28, 95% CI: 1.06-4.88), and overactive thyroid/parathyroid
      (aOR: 3.49, 95% CI: 1.29-9.50) were associated with single falls. Frailty (aOR:
      2.81, 95% CI: 1.11-7.09), decreased body height (aOR: 3.15, 95% CI: 1.52-6.54)
      and taking sedatives/hypnotics (aOR: 4.23, 95% CI: 2.06-8.67) were associated
      with recurrent falls. Previous falls (aOR: 2.64, 95% CI: 1.44-4.84 for single
      falls; aOR: 5.26, 95% CI: 2.61-10.60 for recurrent falls) were associated with
      all falls. CONCLUSION: Different intervention strategies should be developed for
      single and recurrent fallers.

PMID- 23872175
TI  - 'Big data', Hadoop and cloud computing in genomics.
AB  - Since the completion of the Human Genome project at the turn of the Century,
      there has been an unprecedented proliferation of genomic sequence data. A
      consequence of this is that the medical discoveries of the future will largely
      depend on our ability to process and analyse large genomic data sets, which
      continue to expand as the cost of sequencing decreases. Herein, we provide an
      overview of cloud computing and big data technologies, and discuss how such
      expertise can be used to deal with biology's big data sets. In particular, big
      data technologies such as the Apache Hadoop project, which provides distributed
      and parallelised data processing and analysis of petabyte (PB) scale data sets
      will be discussed, together with an overview of the current usage of Hadoop
      within the bioinformatics community. 

PMID- 23872176
TI  - Influence of MCC II fraction and storage conditions on pellet properties.
AB  - Microcrystalline cellulose II (MCC II)--a polymorph of commonly used MCC I--was
      introduced as new pelletization aid in wet-extrusion/spheronization leading to
      fast disintegrating pellets. Previous investigations suggested that pellet
      properties were influenced by the fraction of MCC II. Furthermore, it is unknown
      whether the storage conditions can affect the disintegration behavior. Therefore,
      the effects of MCC II fraction and the storage conditions on several pellet
      properties were investigated. MCC II-based pellets were prepared of pure MCC II
      or binary mixtures containing 10-50% (steps of 10%) MCC II as pelletization aid
      and theophylline, chloramphenicol or lactose. The pellets were characterized by
      their aspect ratio, equivalent diameter, water content, tensile strength,
      porosity as well as shrinking, and disintegration behavior and drug release
      according to their MCC II fraction. Furthermore, the pellets were stored at
      different relative humidities (0-97%rh), and the influence on their
      disintegration and drug release was investigated. With increasing MCC II
      fraction, the pellets became lager in size, decreased their porosity, and
      required higher water contents for spheronization. Moreover, the disintegration
      time increased and the disintegration itself was incomplete. Furthermore, the
      storage conditions had an impact on the disintegration properties of MCC II-based
      pellets. The disintegrating was affected irreversibly after storage at high
      humidity (80-97%rh) resulting in a slow drug release. Therefore, MCC II-based
      pellets need to be stored below 80%rh to secure a fast disintegration. A better
      knowledge of the properties of MCC II-based pellets was obtained providing a
      basis for a successful manufacturing and adequate storage of MCC II-based pellets
      prepared by extrusion/spheronization.

PMID- 23872177
TI  - Ionically-crosslinked milk protein nanoparticles as flutamide carriers for
      effective anticancer activity in prostate cancer-bearing rats.
AB  - In this study, casein (CAS) nanoparticles were used to encapsulate the
      hydrophobic anticancer drug, flutamide (FLT), aiming at controlling its release,
      enhancing its anti-tumor activity, and reducing its hepatotoxicity. The
      nanoparticles were prepared by emulsification of CAS, at pH below its isoelectric
      point, and stabilized via ionic-crosslinking with sodium tripolyphosphate (TPP).
      The nanoparticles were spherical and positively charged with a size below 100 nm
      and exhibited a sustained drug release up to 4 days. After intravenous
      administration into prostate cancer-bearing rats for 28 days, FLT-loaded CAS
      nanoparticles showed a higher anti-tumor efficacy as revealed by a significantly
      higher % reduction in PSA serum level (75%) compared to free FLT (55%). Moreover,
      the nanoparticles demonstrated a marked reduction in the relative weights of both
      prostate tumor and seminal vesicle (43% and 32%) compared to free FLT (12% and
      18%), respectively. A significantly higher anti-proliferative, anti-angiogenic,
      and apoptotic effects was demonstrated by the nanoparticles compared to drug
      solution as evidenced by their ability to decrease the expression of the
      proliferative marker (Ki-67) and reduce the level of tumor angiogenic markers
      (VEGF and IGF-1) as well as their ability to activate caspase-3 with subsequent
      induction of apoptosis in prostate cancer cells. Conclusively, these novel
      ionically-crosslinked milk protein nanovehicles offer a promising carrier to
      allow controlled intravenous delivery of hydrophobic anticancer drugs.

PMID- 23872178
TI  - Formulation of poorly water-soluble drugs via coacervation--a pilot study using
      febantel.
AB  - In this study, febantel was dissolved under increased temperature in a nonionic
      surfactant Lutrol L44(r) and subsequently mixed into an aqueous maltodextrin
      solution. After 8h under static conditions, coacervation or phase separation took
      place. (1)H NMR spectra and HPLC analysis showed that the upper phase contained
      mainly all febantel, while no febantel was detected in the lower phase.
      Fluorescent microscopy showed that maltodextrin is distributed in the lower
      phase. Coacervation proved to be a promising formulation technology for certain
      poorly water-soluble drugs, such as febantel. The coacervate phase showed an
      increase in in vitro dissolution kinetics, compared to Rintal(r) granules. These
      results were confirmed in an in vivo study performed on dogs. Febantel and
      fenbendazole showed a significant increase in plasma concentration compared to
      Rintal(r) granules. Further studies have to be performed to transform coacervates
      into a solid dosage form and to prove broad applicability to other poorly soluble
      drugs. 

PMID- 23872179
TI  - Evaluation of critical process parameters for intra-tablet coating uniformity
      using terahertz pulsed imaging.
AB  - The purpose of this study was to evaluate the intra-tablet coating uniformity and
      the identification of critical process parameters in an active pan coating
      process using terahertz pulsed imaging (TPI). A design of experiments (DoE) was
      performed with drum load, drum speed, spray rate, run duration and spray pressure
      as factors. Different measures of intra-tablet uniformity were investigated: the
      average thickness on the individual tablet faces, spatial variation in layer
      thickness over the tablet surface, and the coefficient of variation (CV(intra)).
      Data analysis revealed that the process parameters in the investigated parameter
      space had hardly any influence on the difference in layer thickness of the tablet
      faces and centre band. No increase or decrease in layer thickness--as described
      in the literature--was found towards the edges of the tablet face. In overwetted
      process conditions a higher layer thickness at the centre band edges could be
      observed. Still, the highest variability in coating thickness was found along the
      circumference of the centre band rather than the height. In general, higher
      CV(intra) of layer thickness were found on the centre bands in comparison with
      the tablet faces. The analysis of the DoE model revealed that the run duration
      had the highest influence on the CV(intra) on the tablet faces. TPI showed high
      potential in the assessment of intra-tablet uniformity and layer thickness
      distributions over the whole tablet surface. It was successfully used to identify
      critical process parameters regarding intra-tablet coating uniformity.

PMID- 23872181
TI  - Direct and indirect photodegradation of estriol in the presence of humic acid,
      nitrate and iron complexes in water solutions.
AB  - The photochemical behavior of a natural estrogen estriol (E3) was investigated in
      the presence of the natural photoreactive constituents including nitrate,
      iron(III), and humic acid (HA). The direct photodegradation of E3 increased with
      increasing incident light intensity, decreasing initial concentration of E3 and
      increasing pH in the range of 6.0 to 10.0. The direct photodegradation of the
      deprotonated speciation of E3 was much faster than that of its protonated form.
      The presence of NO3(-) and iron(III) promoted the photochemical loss of E3 in the
      aqueous solutions. The quenching experiments verified that hydroxyl radicals were
      predominantly responsible for the indirect photodegradation of E3. HA could act
      as photosensitizer, light screening agent and free radical quencher. For the
      first time, the enhancement or inhibition effect of HA on photodegradation was
      found to depend on the irradiation light intensity. HA enhanced the
      photodegradation of E3 under sunlight or weak irradiation of simulated sunlight.
      In contrast, under high irradiation light intensity, HA inhibited the
      photodegradation. The hydroxylation photoproducts were identified using GC-MS and
      the photodegradation pathway of E3 was proposed. 

PMID- 23872180
TI  - Lipid-polymer hybrid nanoparticles as a new generation therapeutic delivery
      platform: a review.
AB  - Lipid-polymer hybrid nanoparticles (LPNs) are core-shell nanoparticle structures
      comprising polymer cores and lipid/lipid-PEG shells, which exhibit complementary
      characteristics of both polymeric nanoparticles and liposomes, particularly in
      terms of their physical stability and biocompatibility. Significantly, the LPNs
      have recently been demonstrated to exhibit superior in vivo cellular delivery
      efficacy compared to that obtained from polymeric nanoparticles and liposomes.
      Since their inception, the LPNs have advanced significantly in terms of their
      preparation strategy and scope of applications. Their preparation strategy has
      undergone a shift from the conceptually simple two-step method, involving
      preformed polymeric nanoparticles and lipid vesicles, to the more principally
      complex, yet easier to perform, one-step method, relying on simultaneous self
      assembly of the lipid and polymer, which has resulted in better products and
      higher production throughput. The scope of LPNs' applications has also been
      extended beyond single drug delivery for anticancer therapy, to include
      combinatorial and active targeted drug deliveries, and deliveries of genetic
      materials, vaccines, and diagnostic imaging agents. This review details the
      current state of development for the LPNs preparation and applications from which
      we identify future research works needed to bring the LPNs closer to its clinical
      realization. 

PMID- 23872182
TI  - A coupled biogeochemical-Dynamic Energy Budget model as a tool for managing fish
      production ponds.
AB  - The sustainability of semi-intensive aquaculture relies on management practices
      that simultaneously improve production efficiency and minimize the environmental
      impacts of this activity. The purpose of the present work was to develop a
      mathematical model that reproduced the dynamics of a semi-intensive fish earth
      pond, to simulate different management scenarios for optimizing fish production.
      The modeling approach consisted of coupling a biogeochemical model that simulated
      the dynamics of the elements that are more likely to affect fish production and
      cause undesirable environmental impacts (nitrogen, phosphorus and oxygen) to a
      fish growth model based on the Dynamic Energy Budget approach. The biogeochemical
      sub-model successfully simulated most water column and sediment variables. A good
      model fit was also found between predicted and observed white seabream (Diplodus
      sargus) growth data over a production cycle. In order to optimize fish
      production, different management scenarios were analysed with the model (e.g.
      increase stocking densities, decrease/increase water exchange rates,
      decrease/increase feeding rates, decrease phosphorus content in fish feeds,
      increase food assimilation efficiency and decrease pellets sinking velocity) to
      test their effects on the pond environment as well as on fish yields and effluent
      nutrient discharges. Scenarios were quantitatively evaluated and compared using
      the Analytical Hierarchical Process (AHP) methodology. The best management
      options that allow the maximization of fish production while maintaining a good
      pond environment and minimum impacts on the adjacent coastal system were to
      double standard stocking densities and to improve food assimilation efficiency. 

PMID- 23872183
TI  - Neural network model for the prediction of PM10 daily concentrations in two sites
      in the Western Mediterranean.
AB  - An artificial neural network (ANN) was developed and tested to forecast PM10
      daily concentration in two contrasted environments in NE Spain, a regional
      background site (Montseny), and an urban background site (Barcelona-CSIC), which
      was highly influenced by vehicular emissions. In order to predict 24-h average
      PM10 concentrations, the artificial neural network previously developed by
      Caselli et al. (2009) was improved by using hourly PM concentrations and
      deterministic factors such as a Saharan dust alert. In particular, the model
      input data for prediction were the hourly PM10 concentrations 1-day in advance,
      local meteorological data and information about air masses origin. The forecasted
      performance indexes for both sites were calculated and they showed better results
      for the regional background site in Montseny (R(2)=0.86, SI=0.75) than for urban
      site in Barcelona (R(2)=0.73, SI=0.58), influenced by local and sometimes
      unexpected sources. Moreover, a sensitivity analysis conducted to understand the
      importance of the different variables included among the input data, showed that
      local meteorology and air masses origin are key factors in the model forecasts.
      This result explains the reason for the improvement of ANN's forecasting
      performance at the Montseny site with respect to the Barcelona site. Moreover,
      the artificial neural network developed in this work could prove useful to
      predict PM10 concentrations, especially, at regional background sites such as
      those on the Mediterranean Basin which are primarily affected by long-range
      transports. Hence, the artificial neural network presented here could be a
      powerful tool for obtaining real time information on air quality status and could
      aid stakeholders in their development of cost-effective control strategies. 

PMID- 23872184
TI  - Spatiotemporal distribution of 137Cs in the sea surrounding Japanese Islands in
      the decades before the disaster at the Fukushima Daiichi Nuclear Power Plant in
      2011.
AB  - The historic spatiotemporal distribution of 137Cs in the seawaters and sea-floor
      sediments adjacent to nuclear power plants in Japan are summarized, using data
      obtained over a period of time more than 20 years prior to the disaster at the
      Fukushima Daiichi Nuclear Power Plant in 2011. Relatively uniform distributions
      of 137Cs were observed both in the surface seawaters (1 m in depth) and in deeper
      seawaters (10 to 30 m above the seabed and ranging from tens to hundreds of
      meters in depth) independent of the geographical position, although lower
      concentrations were observed in significantly deeper bottom seawaters.
      Conversely, there were wide variations in 137Cs levels between sediments, such
      that higher 137Cs concentrations were observed in the deeper sampling locations.
      A mathematical model describing the successive transfer of 137Cs from surface
      waters through deeper waters to sediments suggested that the transfer rate of
      137Cs from deep water to the sediments, and the loss rate from bottom sediments,
      were both greater than the transfer rate from surface water to deeper water. It
      was found that the calculated regression lines for 137Cs depletion rates over
      time for surface waters, deeper waters, and sediments were approximately parallel
      when plotted on a semi-logarithmic coordinate system, regardless of the sampling
      location. A radionuclide depletion half-life was calculated to be 4 months to 16
      years with the geometric mean of 2.22 y for the sediments in the Fukushima
      region, suggesting that nuclear contamination will be remediated over time
      through sediment redistribution processes such as remobilization, bioturbation,
      and migration due to sea currents.

PMID- 23872185
TI  - Pretreated cheese whey wastewater management by agricultural reuse: chemical
      characterization and response of tomato plants Lycopersicon esculentum Mill.
      under salinity conditions.
AB  - The agricultural reuse of pretreated industrial wastewater resulting from cheese
      manufacture is shown as a suitable option for its disposal and management. This
      alternative presents attractive advantages from the economic and pollution
      control viewpoints. Pretreated cheese whey wastewater (CWW) has high contents of
      biodegradable organic matter, salinity and nutrients, which are essential
      development factors for plants with moderate to elevated salinity tolerance. Five
      different pretreated CWW treatments (1.75 to 10.02 dS m(-1)) have been applied in
      the tomato plant growth. Fresh water was used as a control run (average salinity
      level=1.44 dS m(-1)). Chemical characterization and indicator ratios of the
      leaves, stems and roots were monitored. The sodium and potassium leaf
      concentrations increased linearly with the salinity level in both cultivars, Roma
      and Rio Grande. Similar results were found in the stem sodium content. However,
      the toxic sodium accumulations in the cv. Roma exceeded the values obtained in
      the cv. Rio Grande. In this last situation, K and Ca uptake, absorption,
      transport and accumulation capacities were presented as tolerance mechanisms for
      the osmotic potential regulation of the tissues and for the ion neutralization.
      Consequently, Na/Ca and Na/K ratios presented lower values in the cv. Rio Grande.
      Na/Ca ratio increased linearly with the salinity level in leaves and stems,
      regardless of the cultivar. Regarding the Na/K ratio, the values demonstrated
      competition phenomena between the ions for the cv. Rio Grande. Despite the high
      chloride content of the CWW, no significant differences were observed for this
      nutrient in the leaves and stems. Thus, no nitrogen deficiency was demonstrated
      by the interaction NO3(-)/Cl(-). Nitrogen also contributes to maintain the water
      potential difference between the tissues and the soil. Na, P, Cl and N radicular
      concentrations were maximized for high salinity levels (>=2.22 dS m(-1)) of the
      pretreated CWW.

PMID- 23872186
TI  - Microbiological evaluation of water during the 2011 flood crisis in Thailand.
AB  - In 2011, a severe flood occurred in Thailand, covering nearly half the country in
      water for several months. The contamination of floodwater and subsequent
      contamination of water for human consumption could have potentially led to a
      widespread health crisis. However, to date, no study has been conducted to
      determine the safety of the waters used for human consumption in Thailand during
      the severe flood. Therefore, we conducted microbiological analysis of 4 kinds of
      water (floodwater, river water, tap water, and filtered tap water) collected from
      industrial and residential areas that were damaged due to flooding. Higher net
      levels of bacteria were found in water with a higher turbidity. No clear trend
      was observed in the pH value of all 4 water samples. The level of total bacterial
      contamination in the water samples was estimated by real-time quantitative
      polymerase chain reaction (PCR). Eleven of the 12 tap water samples and all of
      the filtered tap water samples had a total bacterial load that exceeded the Thai
      water quality standards. One of the tap water samples and one of the filtered tap
      water samples were found to be positive for Shigella sp., although none of the
      floodwater samples showed detectable levels of this pathogen as determined by PCR
      analysis. One of the samples of floodwater was also found to be positive for
      Leptospira sp., but none of the tap water or filtered tap water samples were
      positive. Most of the tap water samples and all filtered tap water samples were
      found to be contaminated with Vibrio cholerae. Bacterial contamination in water
      samples was also analyzed by denaturing gradient gel electrophoresis (DGGE)
      analysis. These results revealed that several microorganisms were transferred via
      floodwater to different areas in the central part of Thailand and cross
      contaminated between floodwater and water for human consumption. 

PMID- 23872187
TI  - Toxicity assessment of metoprolol and its photodegradation mixtures obtained by
      using different type of TiO2 catalysts in the mammalian cell lines.
AB  - Toxicity of metoprolol (MET) alone and in mixtures with its photocatalytic
      degradation intermediates obtained by using TiO2 Wackherr and Degussa P25 under
      UV irradiation in the presence of O2 was evaluated in vitro in a panel of three
      histologically different cell lines: rat hepatoma (H-4-II-E), human colon
      adenocarcinoma (HT-29) and human fetal lung (MRC-5). Both catalysts promoted a
      time-dependent increase in the toxicity of the photodegradation products, and
      those obtained using Degussa P25 photocatalyst were more toxic. The most
      pronounced and selective toxic action of MET and products of its photodegradation
      was observed in the hepatic cell line. The higher toxicity of the mixtures
      obtained using Degussa P25 catalyst could be explained by a different mechanism
      of MET degradation, i.e. by the presence or higher concentrations of some
      intermediates. Although the concentrations of intermediates obtained using TiO2
      Wackherr catalyst were higher, they did not affect significantly the growth of
      the examined cell lines, indicating their lower toxicity. This suggests that a
      treatment aiming at complete mineralization should be performed bearing in mind
      that the type of catalyst, the concentration of target molecule, and the duration
      of the process are significant factors that determine the nature and toxicity of
      the resulting mixtures. Although the EC50 values of MET obtained in mammalian
      cell lines were higher compared to the bioassays for lower trophic levels, the
      time-dependent promotion of toxicity of degradation mixtures should be attributed
      to the higher sensitivity of mammalian cell bioassays. 

PMID- 23872188
TI  - Synergistically acting PLA2: peptide hemorrhagic complex from Daboia russelii
      venom.
AB  - Snake venoms are complex mixture of enzymatic and non-enzymatic proteins. Non
      covalent protein-protein interaction leads to protein complexes, which bring
      about enhanced pharmacological injuries by their synergistic action. Here we
      report identification and characterization of a new Daboia russelii hemorrhagic
      complex I (DR-HC-I) containing phospholipase A2 (PLA2) and non-enzymatic peptide.
      DR-HC-I was isolated from the venom of D. russelii by CM-Shepadex-C25 and gel
      permeation chromatography. Individual components were purified and identified by
      RP-HPL chromatography, mass spectrometry and N-terminal amino acid sequencing. DR
      HC-I complex was lethal to mice with the LD50 dose of 0.7 mg/kg body weight with
      hemorrhagic and neurotoxic properties. DR-HC-I complex consists of non
      hemorrhagic PLA2 and neurotoxic non-enzymatic peptide. The non-enzymatic peptide
      quenched the intrinsic fluorescence of PLA2 in a dose dependent manner,
      signifying the synergistic interaction between two proteins. PLA2 and peptide
      toxin in a 5:2 M ratio induced skin hemorrhage in mice with MHD 20 MUg. However,
      addition of ANS (1-Anilino-8-naphthalene sulfonate) to DR-HC-I complex inhibited
      skin hemorrhagic effect and also synergic interaction. But there was no impact on
      PLA2 due to this synergistic interaction, and indirect hemolytic or plasma re
      calcification activity. However, the synergistic interaction of PLA2 and non
      enzymatic peptide contributes to the enhanced venom-induced hemorrhage and
      toxicity of Daboia russellii venom.

PMID- 23872189
TI  - Synthesis and tandem mass spectrometry of chlorinated triacylglycerols.
AB  - The incorporation of 9,10-dichlorooctadecanoyl groups using enzyme-catalyzed
      acylation and protecting group strategies yielded specific regioisomers of di-
      and tetrachlorinated triacylglycerols. Hexachloro- and hexabromotriacylglycerols
      were synthesized by addition of chlorine or bromine to tri-(cis-9
      octadecenoyl)glycerol. Upon electrospray ionization and tandem mass spectrometry,
      the sodium adduct ions of all compounds containing a 9,10-dichlorooctadecanoyl
      group readily lost two molecules of HCl when subjected to collision-induced
      dissociation. A mechanism describing sequential HCl losses and the formation of a
      conjugated diene is proposed for the loss of both vicinal chlorine atoms from an
      alkyl chain. This characteristic fragmentation behavior and the availability of
      characterized standards will facilitate the development of quantitative
      analytical methods for the determination of chlorinated triacylglycerols in lipid
      mixtures isolated from marine and other biological sources. 

PMID- 23872190
TI  - Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for
      memory reconsolidation in trace fear conditioning.
AB  - Mounting evidence suggests that long-lasting, protein synthesis-dependent changes
      in synaptic strength accompany both the initial acquisition and subsequent recall
      of specific memories. Within brain areas thought to be important for learning and
      memory, including the hippocampus, learning-related plasticity is likely mediated
      in part by NMDA receptor activation and experience-dependent changes in gene
      expression. In the present study, we examined the role of activity-regulated
      cytoskeletal-associated protein (Arc/Arg3.1) expression in the acquisition,
      recall, and reconsolidation of memory in a trace fear conditioning paradigm.
      First, we show that the expression of Arc protein in ventral hippocampus (VH) is
      dramatically enhanced by memory recall 24h after the acquisition of trace fear
      conditioning, and that both memory recall and the associated recall-induced
      enhancement of Arc expression are blocked by pre-training administration of 2
      amino-5-phosphonovaleric acid (APV). Next, we show that while infusion of Arc
      antisense oligodeoxynucleotides (ODNs) into VH prior to testing had little effect
      on memory recall, it significantly reduced both Arc protein expression and
      freezing behavior during subsequent testing sessions. Collectively, these results
      suggest that Arc/Arg3.1 protein plays an important functional role in both the
      initial acquisition of hippocampal-dependent memory and the reconsolidation of
      these memories after recall. 

PMID- 23872191
TI  - Adjuvant treatment for endometrial cancer: literature review and recommendations
      by the Comite de l'evolution des pratiques en oncologie (CEPO).
AB  - OBJECTIVE: Despite the very good prognosis of endometrial cancer, a number of
      patients with localized disease relapse following surgery. Therefore, various
      adjuvant therapeutic approaches have been studied. The objective of this review
      is to evaluate the efficacy and safety of neoadjuvant and adjuvant therapies in
      patients with resectable endometrial cancer and to develop evidence-based
      recommendations. METHODS: A review of the scientific literature published between
      January 1990 and June 2012 was performed. The search was limited to published
      phase III clinical trials and meta-analyses evaluating the efficacy of
      neoadjuvant or adjuvant therapies in patients with endometrial carcinoma or
      carcinosarcoma. A total of 23 studies and five meta-analyses were identified.
      RESULTS: The selected literature showed that in patients with a low risk of
      recurrence, post-surgical observation is safe and recommended in most cases.
      There are several therapeutic modalities available for treatment of endometrial
      cancers with higher risk of recurrence, including vaginal brachytherapy, external
      beam radiotherapy, chemotherapy, or a combination of these. CONCLUSIONS:
      Considering the evidence available to date, the CEPO recommends the following:
      (1)post-surgical observation for most patients with a low recurrence risk;
      (2)adjuvant vaginal brachytherapy for patients with an intermediate recurrence
      risk; (3)adjuvant pelvic radiotherapy with or without vaginal brachytherapy for
      patients with a high recurrence risk; addition of adjuvant chemotherapy may be
      considered as an option for selected patients (excellent functional status, no
      significant co-morbidities, poor prognostic factors); (4)adjuvant chemotherapy
      and pelvic radiotherapy with or without brachytherapy and para-aortic irradiation
      for patients with advanced disease;

PMID- 23872192
TI  - Abdominal radical trachelectomy: Is it safe for IB1 cervical cancer with tumors
      >= 2 cm?
AB  - OBJECTIVES: As abdominal radical trachelectomy (ART) has become a favored
      fertility-sparing procedure, the relative contraindication of a tumor >= 2 cm in
      size has been questioned. The aim of the study was to report the surgical and
      oncological safety of ART for selected patients with cervical cancer >= 2 cm in
      size. METHODS: We conducted a retrospective review of a prospectively maintained
      database of patients undergoing ART at our institution from 04/2004 to 01/2013.
      The largest tumor dimension was determined by physical exam, MRI or final
      pathology. Clinical and pathological data were tabulated. All patients were
      followed postoperatively. RESULTS: Of the 133 patients who underwent planned ART,
      62 (46.6%) had tumors >= 2 cm in size (2-4 cm). Forty-six patients were
      documented by exam or MRI, while 16 were documented by pathology reports. The
      mean age was 30.4 years, and 42 patients (67.7%) were nulliparous. Fifty (80.7%)
      had squamous carcinoma, 7 (11.3%) had adenocarcinoma and 5 (8%) had adenosquamous
      carcinoma. Due to frozen-section results, 6 patients (9.7%) underwent an
      immediate hysterectomy. Due to high-risk features on final pathology, 27 patients
      (43.5%) were treated with adjuvant chemotherapy (n=20) or chemoradiation (n=7).
      In total, 55 (88.7%) of 62 patients with a tumor >= 2 cm in size preserved their
      fertility potential. Among these patients, 35 underwent ART without further
      adjuvant treatment. At a median follow-up of 30.2 months, there were no
      recurrences. CONCLUSIONS: Expanding the ART inclusion criteria to cervical
      cancers >= 2 cm in size allows a fertility-sparing procedure in young women who
      would have otherwise been denied the option with no apparent compromise in
      oncological outcome. However, this may result in higher rates of conversion to
      hysterectomy or the need for adjuvant chemotherapy/or chemoradiation.

PMID- 23872193
TI  - Nicorandil ameliorates mitochondrial dysfunction in doxorubicin-induced heart
      failure in rats: possible mechanism of cardioprotection.
AB  - Despite of its known cardiotoxicity, doxorubicin is still a highly effective anti
      neoplastic agent in the treatment of several cancers. In the present study, the
      cardioprotective effect of nicorandil was investigated on hemodynamic alterations
      and mitochondrial dysfunction induced by cumulative administration of doxorubicin
      in rats. Doxorubicin was injected i.p. over 2 weeks to obtain a cumulative dose
      of 18 mg/kg. Nicorandil (3 mg/kg/day) was given orally with or without
      doxorubicin treatment. Heart rate and aortic blood flow were recorded 24 h after
      receiving the last dose of doxorubicin. Rats were then sacrificed and hearts were
      rapidly excised for estimation of caspase-3 activity, phosphocreatine and adenine
      nucleotides contents in addition to cytochrome c, Bcl2, Bax and caspase 3
      expression. Moreover, mitochondrial oxidative phosphorylation capacity, creatine
      kinase activity and oxidative stress markers were measured together with the
      examination of DNA fragmentation and ultrastructural changes. Nicorandil was
      effective in alleviating the decrement of heart rate and aortic blood flow and
      the state of mitochondrial oxidative stress induced by doxorubicin
      cardiotoxicity. Nicorandil also preserved phosphocreatine and adenine nucleotides
      contents by restoring mitochondrial oxidative phosphorylation capacity and
      creatine kinase activity. Moreover, nicorandil provided a significant
      cardioprotection via inhibition of apoptotic signaling pathway, DNA fragmentation
      and mitochondrial ultrastructural changes. Interestingly, nicorandil did not
      interfere with cytotoxic effect of doxorubicin against the growth of solid
      Ehrlich carcinoma. In conclusion, nicorandil was effective against the
      development of doxorubicin-induced heart failure in rats as indicated by
      improvement of hemodynamic perturbations, mitochondrial dysfunction and
      ultrastructural changes without affecting its antitumor activity.

PMID- 23872194
TI  - p-Terphenyl curtisian E inhibits in vitro platelet aggregation via cAMP elevation
      and VASP phosphorylation.
AB  - Mushrooms possess untapped source of enormous natural compounds showing anti
      inflammatory, antioxidant and anti-platelet activities. Paxillus curtisii, wild
      mushroom, is a rich source of curtisian E (CE) reported for neuroprotective
      effects; however, its anti-platelet effect was unknown. Here, therefore, we
      investigated the anti-platelet activity of CE in rat platelets. Curtisian E (12.5
      200MUM) attenuated collagen (2.5MUg/ml), thrombin (0.1U/ml) and ADP (10MUM)
      induced platelet aggregation in vitro. Likewise, CE diminished intracellular
      calcium and adenosine triphosphate (ATP) release in collagen activated platelets.
      Fibrinogen binding and fibronectin adhesion to platelets were also inhibited.
      While CE downregulated c-jun N-terminal kinase (JNK), extracellular signal
      regulated kinase (ERK), p38, and Akt dose dependently in collagen stimulated
      platelets, it upregulated intraplatelet cyclic adenosine monophosphate (cAMP) and
      vasodilator-stimulated-phosphoprotein (VASP) phosphorylation. Protein kinase A
      inhibitor (H-89) markedly inhibited p-VASP(157) protein expression, suggesting
      that cAMP-PKA-VASP(157) pathway may mediate its anti-platelet effect and thus CE
      could be considered as a potential anti-thrombotic agent. 

PMID- 23872195
TI  - The new oral anticoagulants in atrial fibrillation: once daily or twice daily?
AB  - The new anticoagulants (NOACs) tested for prevention or treatment of venous
      thromboembolism (VTE), stroke prevention in atrial fibrillation (AF), and acute
      coronary syndromes (ACS) differ in bioavailability, metabolism, route of
      excretion and interaction with other drugs, but have remarkably similar
      pharmacokinetics, with very similar half lives. However the choice of dosing
      regimens in different clinical conditions has been different for the various
      NOACs, and has been established on the basis of widely different considerations,
      including the clinical setting (venous versus arterial thrombosis), the
      indications (prophylaxis versus treatment), the likelihood of concomitant
      antiplatelet drugs, and marketing opportunities; these latter were based on the
      knowledge that patients' compliance is generally better with once daily than with
      twice daily dosing. Current prevailing wisdom is that peak plasma drug
      concentrations are important determinants of bleeding: since a fractioning of the
      total daily dose into a twice daily regimen reduces peak plasma drug
      concentrations compared with once daily dosing, this should maximize safety.
      However, recent pharmacokinetic analyses of a phase II study with edoxaban in AF
      found that bleeding, with the same daily dosing, was less frequent with once
      daily dosing than with twice daily dosing, and correlated - better than other
      pharmacokinetic parameters - through drug concentrations. Higher rates of
      bleeding have been also reported with the twice daily versus once daily dosing of
      darexaban in a phase II study in ACS. These results may lead to a rethinking on
      the pathophysiology of bleeding in the setting of anticoagulation. 

PMID- 23872196
TI  - Differential actions of the prostacyclin analogues treprostinil and iloprost and
      the selexipag metabolite, MRE-269 (ACT-333679) in rat small pulmonary arteries
      and veins.
AB  - The prostacyclin (IP) receptor agonists, treprostinil, iloprost and the selexipag
      metabolite, MRE-269 (ACT-333679) were evaluated in rat distal pulmonary blood
      vessels. Small pulmonary arteries and veins were pre-contracted with the
      thromboxane mimetic, U46619 (25 and 100nM, respectively), and relaxation
      determined with and without IP receptor antagonists, RO1138452 and RO3244794. In
      arteries, treprostinil was a more potent vasorelaxant than iloprost, while the
      efficacy of iloprost was greater. In pulmonary arteries, treprostinil-induced
      relaxation was essentially abolished by both IP antagonists (1MUM), while
      responses to iloprost were partially inhibited. Both treprostinil and iloprost
      were equipotent, prominently relaxing pulmonary veins with responses being
      similarly and partially sensitive to IP antagonists. In contrast, RO1138452
      failed to inhibit relaxations to MRE-269 in either pulmonary arteries or veins,
      suggesting no involvement of typical IP receptors. Thus, rat pulmonary tissues
      cannot be considered appropriate to assess classical IP receptors using the
      proposed highly selective non-prostanoid agonist MRE-269, contrasting with the IP
      receptor agonism profile of prostacyclin analogues, iloprost and treprostinil. 

PMID- 23872197
TI  - The influence of reading ability on subsequent changes in verbal IQ in the
      teenage years.
AB  - Intelligence Quotient (IQ) is regularly used in both education and employment as
      a measure of cognitive ability. Although an individual's IQ is generally assumed
      to stay constant across the lifespan, a few studies have suggested that there may
      be substantial variation at the individual level. Motivated by previous reports
      that reading quality/quantity has a positive influence on vocabulary acquisition,
      we hypothesised that reading ability in the early teenage years might contribute
      to changes in verbal IQ (VIQ) over the next few years. We found that good readers
      were more likely to experience relative improvements in VIQ over time, with the
      reverse true for poor readers. These effects were largest when there was a
      discrepancy between Time 1 reading ability and Time 1 VIQ. In other words, VIQ
      increases tended to be greatest when reading ability was high relative to VIQ.
      Additional analyses supported these findings by showing that variance in VIQ
      change associated with Time 1 behaviour was also associated with independent
      measurements of brain structure. Our finding that reading in the early teenage
      years can predict a significant proportion of the variance in subsequent VIQ
      change has implications for targeted education in both home and school
      environments. 

PMID- 23872198
TI  - Chinese dyslexics show neural differences in morphological processing.
AB  - Previous behavioral studies have suggested that morphological awareness is
      impaired in Chinese children with reading disability (RD), but how this is
      reflected in brain alterations is not known. Using functional magnetic resonance
      imaging (fMRI), the current study compared morphological processing in a RD group
      (11-13 years old) to an age-matched typically developing (TD) group. Participants
      made semantic relatedness judgments to incongruent word pairs that were either
      semantically related but did not share a morpheme or semantically unrelated but
      did share a morpheme. This was compared to conditions where semantic relatedness
      and morphemic information was congruent. A smaller incongruency effect was found
      in left dorsal posterior (BA9) and ventral anterior (BA47) inferior frontal gyrus
      (IFG) in the RD compared to the TD, suggesting that the RD is less sensitive to
      morphological information. This was a specific deficit as a phonological control
      task that manipulated congruency between orthography and phonology did not show
      group differences in the IFG. Moreover, brain activation in the IFG for the
      incongruency effect in the semantic task was negatively correlated with reading
      skill for the RD group only, suggesting that higher skill children with RD may
      rely on a compensatory whole-word strategy by ignoring the morphemic information.

PMID- 23872200
TI  - The GAG database: a new resource to gather genomic annotation cross-references.
AB  - Several institutions provide genomic annotation data, and therefore these data
      show a significant segmentation and redundancy. Public databases allow access,
      through their own methods, to genomic and proteomic sequences and related
      annotation. Although some cross-reference tables are available, they don't cover
      the complete datasets provided by these databases. The Genomic Annotation
      Gathering project intends to unify annotation data provided by GenBank and
      Ensembl. We introduce an intra-species, cross-bank method. Generated results
      provide an enriched set of cross- references. This method allows for identifying
      an average of 30% of new cross-references that can be integrated to other
      utilities dedicated to analyzing related annotation data. By using only sequence
      comparison, we are able to unify two datasets that previously didn't share any
      stable cross-bank accession method. The whole process is hosted by the GenOuest
      platform to provide public access to newly generated cross-references and to
      allow for regular updates (http://gag.genouest.org). 

PMID- 23872199
TI  - Biological impact of preschool music classes on processing speech in noise.
AB  - Musicians have increased resilience to the effects of noise on speech perception
      and its neural underpinnings. We do not know, however, how early in life these
      enhancements arise. We compared auditory brainstem responses to speech in noise
      in 32 preschool children, half of whom were engaged in music training. Thirteen
      children returned for testing one year later, permitting the first longitudinal
      assessment of subcortical auditory function with music training. Results indicate
      emerging neural enhancements in musically trained preschoolers for processing
      speech in noise. Longitudinal outcomes reveal that children enrolled in music
      classes experience further increased neural resilience to background noise
      following one year of continued training compared to nonmusician peers. Together,
      these data reveal enhanced development of neural mechanisms undergirding speech
      in-noise perception in preschoolers undergoing music training and may indicate a
      biological impact of music training on auditory function during early childhood. 

PMID- 23872201
TI  - Impact of MMP-3 and TIMP-3 gene polymorphisms on prostate cancer susceptibility
      in North Indian cohort.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) have been implicated in progression and
      metastases of different tumors. The balance between the MMPs and their natural
      inhibitors (tissue inhibitors of matrix metalloproteinases; TIMP) seem to be an
      important factor related to its role. The purpose of this study was to evaluate
      polymorphisms in the MMP-3 and TIMP-3 genes for their associations with prostate
      cancer (PCa) risk in North Indians. MATERIALS AND METHODS: Genotypes were
      determined by PCR-RFLP (Polymerase Chain Reaction Restriction Fragment Length
      Polymorphism) method in 150 PCa patients and 200 age matched controls of similar
      ethnicity. RESULTS: We found significant association in the MMP-3(1171)5A/6A and
      TIMP-3 (1298) C/T polymorphism with PCa risk. Variant genotype (5A/5A) of MMP
      3(1171)5A/6A polymorphism had a high PCa risk (p=0.037, OR=3.52, 95%CI=1.08
      11.5). Individuals with TIMP-3 (1298) CT genotype as well as T allele showed
      reduced risk of PCa (p<0.001; OR=0.31; 95%CI=0.18-0.52, and p=0.001; OR=0.49;
      95%CI=0.32-0.75). This effect was even more evident in case of T allele carrier
      (CT+TT) (p<0.001; OR=0.36; 95%CI=0.22-0.59). Overall no significant association
      was observed statistically in MMP-3 and TIMP-3 with any of the grading stages and
      smoking habits in PCa. Haplotype analysis of MMP-3 showed that A-5A-A was
      associated with three folds (OR=3.06; 95%CI=1.71-5.47; p<0.001) increased risk in
      PCa patients. CONCLUSION: This is the first reported association between
      polymorphisms in the MMP-3 and TIMP-3 gene and PCa risk and supports the
      hypothesis that the protease/antiprotease balance has an important role. Due to
      the small sample size further investigations need to be done to prove a
      statistical significant correlation between the MMP/TIMP expression and
      clinicopathological parameters.

PMID- 23872202
TI  - XRCC1 polymorphisms and differentiated thyroid carcinoma risk: a meta-analysis.
AB  - The objective of this study is to quantitatively derive a more precise estimation
      of the association between X-ray repair cross-complementing group 1 (XRCC1) gene
      polymorphisms and differentiated thyroid carcinoma risk. A comprehensive
      literature search of three databases was conducted. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated with fixed-effect models and random
      effect models when appropriate. Overall, no association of the XRCC1 Arg399Gln,
      Arg280His, and Arg194Trp polymorphisms with differentiated thyroid carcinoma risk
      was found. In subgroup analyses, a decreased differentiated thyroid carcinoma
      risk was observed among Caucasians (Gln vs. Arg, OR=0.86, 95% CI=0.77-0.96,
      P=0.343 for heterogeneity; Gln/Arg vs. Arg/Arg, OR=0.84, 95% CI=0.71-0.98,
      P=0.229 for heterogeneity; Gln/Gln vs. Arg/Arg, OR=0.77, 95% CI=0.60-0.99,
      P=0.477 for heterogeneity; dominant genetic model, OR=0.82, 95% CI=0.71-0.95,
      P=0.272 for heterogeneity), not among Asians. No publication bias was observed.
      Our results suggest that XRCC1 Arg399Gln polymorphism is not associated with
      differentiated thyroid carcinoma risk, while a decreased risk is observed among
      Caucasian population.

PMID- 23872203
TI  - Hidden ancient repeats in DNA: mapping and quantification.
AB  - We have shown, in a previous paper, that tandem repeating sequences, especially
      triplet repeats, play a very important role in gene evolution. This result led to
      the formulation of the following hypothesis: most of the genomic sequences
      evolved through everlasting acts of tandem repeat expansions with subsequent
      accumulation of changes. In order to estimate how much of the observed sequences
      have the repeat origin we describe the adaptation of a text segmentation
      algorithm, based on dynamic programming, to the mapping of the ancient expansion
      events. The algorithm maximizes the segmentation cost, calculated as the
      similarity of obtained fragments to the putative repeat sequence. In the first
      application of the algorithm to segmentations of genomic sequences, a significant
      difference between the natural sequences and the corresponding shuffled sequences
      is detected. The natural fragments are longer and more similar to the putative
      repeat sequences. As our analysis shows, the coding sequences allow for repeats
      only when the size of the repeated words is divisible by three. In contrast, in
      the non-coding sequences, all repeated word sizes are present. It was estimated,
      that in Escherichia coli K12 genome, about 35.5% of sequence can be detectably
      traced to original simple repeat ancestors. The results shed light on the genomic
      sequence organization, and strongly confirm the hypothesis about the crucial role
      of triplet expansions in gene origin and evolution. 

PMID- 23872204
TI  - Validation of a rapid liquid chromatography-tandem mass spectrometric assay for
      the determination of octreotide plasma concentrations.
AB  - OBJECTIVES: The aim of this study was to develop and validate a fast liquid
      chromatography-tandem mass spectrometric (LC-MSMS) assay to determine circulating
      concentrations of octreotide (a somatostatin analog used in acromegaly and
      neuroendocrine tumors) in patients' plasma samples. DESIGN AND METHODS: 500 MUL
      of heparin-plasma was used to extract the drug on a cation exchanger SPE column,
      and the eluate was injected into a LC-MSMS system. Reversed phase chromatography
      was performed on a phenyl grafted column in isocratic mode. Octreotide and
      internal standard (triptorelin) were identified in positive electrospray
      ionization mode using ion transitions of m/z 512>120 and 890>249, respectively.
      RESULTS: The assay was linear in the concentration range of 0.5-25 ng/mL, with
      intra- and inter-assay imprecisions of <10.6% and <12.2%, respectively. The
      limits of quantification and detection were 0.5 and 0.25 ng/mL. The recovery and
      ion suppression effect ranged between 79.7 and 84.5% and between -8.1 and -21.3%,
      respectively. A subcutaneous injection of 0.1mg octreotide induced a time- and
      patient-dependent surge of peptide concentrations peaking at 2h. CONCLUSION: This
      fast, sensitive, and selective method for quantification of plasma octreotide by
      LC-MSMS might be used to investigate the pharmacokinetic-pharmacodynamic
      relationship, with potential contribution to treatment optimization and
      therapeutic drug monitoring application.

PMID- 23872205
TI  - The age related association is more pronounced for cystatin C estimated GFR than
      for creatinine estimated GFR in primary care patients.
AB  - OBJECTIVES: There is an age associated change in GFR but this association may be
      influenced by the method used. The aims of the present study were to assess the
      association between age and cystatin C and creatinine based glomerular filtration
      rate estimates in primary care patients, and to determine the proportion of
      patients with clinically important renal impairment. MATERIALS AND METHODS: 1552
      samples with simultaneous requests for creatinine and cystatin C from 1552
      primary care patients in the county of Uppsala, Sweden were analysed. MDRD, CKD
      EPI and cystatin C equations were used to calculate glomerular filtration rate
      (GFR) and the associations between GFR and age were explored. RESULTS: The yearly
      change in cystatin C estimated GFR was 1.24 mL/min/1.73 m(2) while the
      corresponding decline for creatinine estimated GFR was 0.76 mL/min/1.73 m(2) for
      MDRD and 0.99 mL/min/1.73 m(2) for CKD-EPI. CONCLUSIONS: The age related
      association with GFR estimates is smaller for creatinine estimates than for
      cystatin C estimates. This leads to differences in the number of patients with
      reduced eGFR detected with the three estimates and the patient treatment will
      depend on the estimate used. This is not coherent with a good patient care and we
      thus need to develop new eGFR equations with better agreement between the
      estimates.

PMID- 23872206
TI  - Challenges in identifying some IgM monoclonal proteins by capillary serum protein
      electrophoresis.

PMID- 23872207
TI  - Phytoestrogens selective for the estrogen receptor beta exert anti-androgenic
      effects in castration resistant prostate cancer.
AB  - Prostate cancer is the leading cause of cancer death in men of the Western world.
      A castration-resistant prostate cancer (CRPC) eventually will arise when a local
      restricted prostate carcinoma was not cured duly by radical prostatectomy or
      radiation therapy. Although androgen ablation therapies are considered the gold
      standard for treatments of advanced prostate cancer there is no curative therapy
      available at present. In previous pre-clinical and clinical trials several
      phytoestrogens were investigated for their anticancer potential in various models
      for prostate cancer. Phytoestrogens feature tumour preventive characteristics and
      most probably are involved in the low incidence rate of hormone related cancers
      in Asian countries. Phytoestrogens such as isoflavones can have a marked impact
      on the most essential therapy target of CRPC i.e. the androgen receptor.
      Furthermore, functional analyses solidified the notion of such drugs as androgen
      antagonistic. Phytoestrogens commonly feature low toxicity combined with a
      potential of targeted therapy. Thus, these drugs qualify for conceivable
      implementation in prostate cancer patients under active surveillance. In
      addition, relapse prevention with these drugs after radical prostatectomy or
      radiation therapy might be considered. This article is part of a Special Issue
      entitled 'Phytoestrogens'. 

PMID- 23872208
TI  - Characterization of the immune response in human paracoccidioidomycosis.
AB  - OBJECTIVES: Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the
      dimorphic fungus Paracoccidioides brasiliensis that presents two main clinical
      forms: the adult form (AF) and the juvenile form (JF); and an asymptomatic form
      denominated PCM-infection (PI). These forms of PCM are related to the immune
      response developed after infection, which has been associated with Th1 and Th2
      responses. However, some PCM characteristics cannot be explained by this balance.
      In this study we aimed to complement the characterization of the immune response
      in PCM, including the newly described T cells subpopulations (Th17, Th9 and
      Th22). METHODS: We analyzed the expression of cytokines and transcription factors
      characteristics of these different subpopulations of CD4(+) T cells in PBMCs from
      PCM patients and a PI group. RESULTS: The results showed that the PI group
      presented a predominant Th1 response; that JF patients were characterized by a
      mixed Th2/Th9 response; and AF patients were characterized by a predominant
      Th17/Th22 response, as well as substantial participation of Th1 cells.
      CONCLUSIONS: These results contribute to the existing knowledge on the immune
      responses associated with resistance or susceptibility to the P. brasiliensis
      infection, and thus could lead to the development of new strategies for patient
      management.

PMID- 23872209
TI  - A population based study of the epidemiology of Herpes Zoster and its
      complications.
AB  - OBJECTIVES: To assess the incidence of Herpes Zoster (HZ) and its complications
      in the Israeli general population and specifically in immune-compromised
      individuals, and to identify risk factors for developing HZ and post-herpetic
      neuralgia (PHN). METHODS: A retrospective database search for newly diagnosed
      cases of HZ and of PHN during 2006-2010 was conducted using the comprehensive
      longitudinal database of Maccabi Health Services. Cox-proportional hazards models
      were used to assess associations between risk factors and HZ and PHN. RESULTS:
      During 2006-2010 there were 28,977 newly diagnosed cases of HZ and 1508 newly
      diagnosed cases of PHN. Incidence density rate of HZ was 3.46 per 1000 person
      years in the total population and 12.8 per 1000 person-years in immune
      compromised patients. HZ and PHN incidence increased sharply with age. 12.4% and
      3.1% of elderly HZ patients (>= 65 years) developed PHN or ophthalmic
      complications, respectively. In multivariable analyses, HZ and PHN were
      associated with female sex, higher socioeconomic status, diabetes mellitus,
      cancer history, and HIV treatment. CONCLUSIONS: Extrapolating to the entire
      Israeli population, we estimate over 24,000 new cases of HZ and 1250 new cases of
      PHN each year. Cost-effectiveness analysis should be performed to determine the
      threshold age for vaccination against HZ.

PMID- 23872210
TI  - Replacement of healthcare-associated MRSA by community-associated MRSA in
      Queensland: confirmation by genotyping.
AB  - OBJECTIVE: To describe the changing prevalence of healthcare- and community
      associated MRSA. METHODS: Susceptibility phenotypes of MRSA were observed from
      2000 to 2012 using routine susceptibility data. Phenotypic definitions of major
      clones were validated by genotyping isolates from a nested period prevalence
      survey in 2011. RESULTS: The predominant healthcare-associated (AUS-2/3 like)
      MRSA phenotype decreased from 42 to 14 isolates per million occasions of service
      in outpatients (P < 0.0001) and from 650 to 75 isolates per million accrued
      patient days in inpatients (P 0.0005), while the respective rates of the
      healthcare-related EMRSA-15 like phenotype increased from 1 to 19 in outpatients
      (P < 0.0001) and from 11 to 83 in inpatients (P < 0.0001) and those of the
      community-associated MRSA phenotype increased from 17 to 296 in outpatients (P <
      0.0001) and from 71 to 486 in inpatients (P < 0.0001). When compared with single
      nucleotide polymorphism genotyping the AUS-2/3 like phenotype had a sensitivity
      and positive predictive value (PPV) for CC239 of 1 and 0.791 respectively, while
      the EMRSA-15 like phenotype had a sensitivity and PPV for CC22 of 0.903 and
      0.774. PVL-positive CA-MRSA, predominantly ST93 and CC30, accounted for 60.8% of
      MRSA, while PVL-negative CA-MRSA, mainly CC5 and CC1, accounted for 21.4%.
      CONCLUSIONS: The initially dominant healthcare-associated MRSA clone has been
      progressively replaced, mainly by four community-associated lineages.

PMID- 23872211
TI  - Dispersive liquid-liquid microextraction followed by high-performance liquid
      chromatography-ultraviolet detection to determination of opium alkaloids in human
      plasma.
AB  - A novel, simple, rapid and sensitive dispersive liquid-liquid microextraction
      method based on the solidification of floating organic drop (DLLME-SFO) combined
      with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was
      used to determine opium alkaloids in human plasma. During the extraction
      procedure, plasma protein was precipitated by using a mixture of zinc sulfate
      solution and acetonitrile. Some effective parameters on extraction were studied
      and optimized. Under the optimum conditions (extraction solvent: 30.0 MUl 1
      undecanol; disperser solvent: 470 MUl acetone; pH: 9; salt addition: 1%(w/v) NaCl
      and extraction time: 0.5 min), calibration curves are linear in the range of 1.5
      1000 MUgl(-1) and limit of detections (LODs) are in the range of 0.5-5 MUgl(-1).
      The relative standard deviations (RSDs) for 100 MUgl(-1) of morphine and codeine,
      10.0 MUgl(-1) of papaverine and 20.0 MUgl(-1) of noscapine in diluted human
      plasma are in the range of 4.3-7.4% (n=5). Finally, the method was successfully
      applied in the determination of opium alkaloids in the actual human plasma
      samples. The relative recoveries of plasma samples spiked with alkaloids are 88
      110.5%. The obtained results show that DLLME-SFO combined with HPLC-UV is a fast
      and simple method for the determination of opium alkaloids in human plasma.

PMID- 23872212
TI  - Identification and analysis of an impurity inducing clinical adverse effect in
      anti-adhesion carboxymethyl chitosan products.
AB  - Controlling and minimizing the adverse effects of drugs are the key issues in
      ensuring the safety of drug therapy. Carboxymethyl chitosan has been widely used
      as an anti-adhesion material. However, recently in China there have been several
      reported instances of conjunctival hyperemia associated with the use of
      carboxymethyl chitosan containing products. Through MS, FTIR, and GC analysis, an
      impurity, diglycolic acid, was discovered in carboxylmethyl chitosan products.
      Pharmacological tests further indicated diglycolic acid has antithrombogenicity
      properties and induces vasodilation, both of which can cause conjunctival
      hyperemia. Thus, through these tests it was ascertained that diglycolic acid was
      the culprit responsible for the adverse clinical effects. Next, emphasis shifted
      to trying to discover the mechanism responsible for generating the diglycolic
      acid. Under strong basic conditions, chloroacetic acid can generate glycolic
      acid, which, upon etherification, can become diglycolic acid. In order to avoid
      future adverse effects, we have established an HPLC method to detect and
      determine diglycolic acid in carboxymethyl chitosan products. This method is
      specific, accurate, and precise, and can be easily implemented into routine
      monitoring practice. Concurrently, a refined method has also been established in
      order to eliminate diglycolic acid from carboxymethyl chitosan. 

PMID- 23872213
TI  - Influence of compost on the mobility of arsenic in soil and its uptake by bean
      plants (Phaseolus vulgaris L.) irrigated with arsenite-contaminated water.
AB  - The influence of compost on the growth of bean plants irrigated with As
      contaminated waters and its influence on the mobility of As in the soils and the
      uptake of As (as NaAs(III)O2) by plant components was studied at various compost
      application rates (3.10(4) and 6.10(4) kg ha(-1)) and at three As concentrations
      (1, 2 and 3 mg kg(-1)). The biomass and As and P concentrations of the roots,
      shoots and beans were determined at harvest time, as well as the chlorophyll
      content of the leaves and nonspecific and specifically bound As in the soil. The
      bean plants exposed to As showed typical phytotoxicity symptoms; no plants
      however died over the study. The biomass of the bean plants increased with the
      increasing amounts of compost added to the soil, attributed to the phytonutritive
      capacity of compost. Biomass decreased with increasing As concentrations,
      however, the reduction in the biomass was significantly lower with the addition
      of compost, indicating that the As phytotoxicity was alleviated by the compost.
      For the same As concentration, the As content of the roots, shoots and beans
      decreased with increasing compost added compared to the Control. This is due to
      partial immobilization of the As by the organic functional groups on the compost,
      either directly or through cation bridging. Most of the As adsorbed by the bean
      plants accumulated in the roots, while a scant allocation of As occurred in the
      beans. Hence, the addition of compost to soils could be used as an effective
      means to limit As accumulation in crops from As-contaminated waters. 

PMID- 23872214
TI  - The influence of expert opinions on the selection of wastewater treatment
      alternatives: a group decision-making approach.
AB  - The application of multiple-attribute decision-making (MADM) to real life
      decision problems suggests that avoiding the loss of information through scenario
      based approaches and including expert opinions in the decision-making process are
      two major challenges that require more research efforts. Recently, a wastewater
      treatment technology selection effort has been made with a 'scenario-based'
      method of MADM. This paper focuses on a novel approach to incorporate expert
      opinions into the scenario-based decision-making process, as expert opinions play
      a major role in the selection of treatment technologies. The sets of criteria and
      the indicators that are used consist of both qualitative and quantitative
      criteria. The group decision-making (GDM) approach that is implemented for
      aggregating expert opinions is based on an analytical hierarchy process (AHP),
      which is the most widely used MADM method. The pairwise comparison matrices
      (PCMs) for qualitative criteria are formed based on expert opinions, whereas, a
      novel approach is proposed for generating PCMs for quantitative criteria. It has
      been determined that the experts largely prefer natural treatment systems because
      they are more sustainable in any scenario. However, PCMs based on expert opinions
      suggest that advanced technologies such as the sequencing batch reactor (SBR) can
      also be appropriate for a given decision scenario. The proposed GDM approach is a
      rationalized process that will be more appropriate in realistic scenarios where
      multiple stakeholders with local and regional societal priorities are involved in
      the selection of treatment technology. 

PMID- 23872215
TI  - Recreational anglers' attitudes, beliefs, and behaviors related to catch-and
      release practices of Pacific salmon in British Columbia.
AB  - The fate of captured and released fish in recreational fisheries depends in large
      part on fisher handling and behavior. As such, there is a need for promoting
      adoption of responsible fishing practices. We interviewed recreational sockeye
      salmon anglers in the lower Fraser River, British Columbia, to assess their
      awareness of responsible fishing practices and identify gaps where improved
      education could promote conservation-oriented behaviors. Based on our interview
      data, we developed three latent class models of salmon angler typologies based
      on: 1) anglers' fishing behaviors and preferences, 2) anglers' perceived risks to
      salmon survival due to post-capture live release, and 3) anglers' level of
      support for education programs. In the first model, we identified salmon-only
      anglers (33% of sample), lake-species specialists (46%), and all-around anglers
      (21%). These classes were differentiated primarily by non-salmon fishing
      activities (e.g., other target species). In the second model, we found four
      classes of anglers who differed with regards to key factors they thought affected
      post-release survival: air exposure (39% of sample); water temperature (24%);
      hook location (22%); and revival effort (15%). In the third model, we found
      anglers were either supporters (73%) or non-supporters (27%) of angler education
      programs. Heterogeneity existed among anglers but we found no correlations in
      angler classes across models, nor any significant demographic or experiential
      predictors of class membership. Respondents generally had high awareness and
      application of catch-and-release best practices, with lake-species specialists
      rating a higher awareness and usage of recommended catch-and-release technique,
      and were significantly more likely to cut the line on deeply hooked fish than
      other groups. Our findings provide resource managers with important insight into
      the attitudes and behaviors of sockeye salmon anglers in the important lower
      Fraser River recreational fishery. Our findings also highlight, however, the need
      for further research on the determinants of angler beliefs and behavior in order
      to customize programs to build anglers' awareness and adoption of responsible
      fishing practices. 

PMID- 23872216
TI  - Assessment of stakeholder perceptions in water infrastructure projects using
      system-of-systems and binary probit analyses: a case study.
AB  - Globally, water management is evolving toward integrating participatory processes
      for decision-making to increase the sustainability of the decision outcome.
      Information about the perceptions and concerns of stakeholders needs to be
      readily available to those involved in the decision-making process early in the
      planning stage to assist in developing viable alternatives that may be
      implementable with limited public opposition and engender general consensus among
      stakeholders. The current literature does not identify an appropriate means to
      incorporate stakeholder views early in the preliminary planning stages without
      requiring relatively large time commitments or the physical presence of the key
      stakeholders for meetings and discussions. This study develops and demonstrates a
      decision-support framework that incorporates the system-of-systems school of
      thought with binary probit analysis to aid in efficient participatory processes
      by providing insight regarding the stakeholders' demographics and select
      behavioral characteristics in a decision-making process. The methodology first
      frames the water system as a system-of-systems, an approach that inherently
      pinpoints the necessity for diverse stakeholder involvement and maps the
      stakeholders in the system's hierarchy. Then, binary probit analyses are used to
      quantify the effect of stakeholder characteristics on the likelihood that (1)
      they perceive or do not perceive a need for new capital-intensive water
      infrastructure, and (2) they support or oppose new capital-intensive water
      infrastructure. A water system decision in the Sacramento-San Joaquin Delta
      serves as a case study to demonstrate the methodology. Data regarding stakeholder
      beliefs and perceptions were collected via a web-based survey deployed throughout
      Southern and Central California The study results indicate that individuals
      between 18 and 25 years, persons living solely with their spouse, persons
      associated with environmental stakeholder groups, and individuals who follow the
      news on local water issues have an increased likelihood of public opposition to
      new water infrastructure in the Sacramento-San Joaquin Delta. These groups would
      be those targeted to mitigate public opposition by measures such as attempting to
      promote further discussion, educational outreach, and incorporating incentives
      such as increasing jobs or incorporating ecosystem rehabilitation efforts around
      the area impacted by the project. 

PMID- 23872217
TI  - Tracking the consequences of morpho-orthographic decomposition using ERPs.
AB  - We examined the effects of morpho-orthographic decomposition on complex word
      processing using a combination of masked priming and ERP recordings. The process
      of morpho-orthographic decomposition was primed by the prior presentation of
      complex non-words (formed by the combination a legal stem and legal affix, e.g.
      huntity, cornity, scanity) as prime stimuli. Targets were semantically
      transparent complex words (e.g., hunter), semantically opaque pseudocomplex words
      (e.g., corner), and simplex words (e.g., scandal) that contained the same stem as
      primes or a different stem (e.g., huntity-hunter vs. farmity-hunter). We found a
      large early (150-200 ms) priming effect for transparent complex words only,
      followed by widely distributed priming effects between 200 and 300 ms and more
      spatially focused N400 priming effects for all types of target. Furthermore, in
      the 150-200 ms time-window, the ERP waveforms generated by pseudocomplex words
      patterned with those of complex words, both of which generated less negative
      going waveforms compared with simplex words. In the N400 time-window, on the
      other hand, complex words differed from both pseudocomplex and simplex words. The
      results provide further support for early morpho-orthographic segmentation
      processes that operate independently of semantic transparency, and suggest that
      the output of these processes only affects the subsequent processing of truly
      complex words.

PMID- 23872219
TI  - Progesterone's role in neuroprotection, a review of the evidence.
AB  - The sex hormone progesterone has been shown to improve outcomes in animal models
      of a number of neurologic diseases, including traumatic brain injury, ischemia,
      spinal cord injury, peripheral nerve injury, demyelinating disease, neuromuscular
      disorders, and seizures. Evidence suggests it exerts its neuroprotective effects
      through several pathways, including reducing edema, improving neuronal survival,
      and modulating inflammation and apoptosis. In this review, we summarize the
      functional outcomes and pathophysiologic mechanisms attributed to progesterone
      treatment in neurologic disease. We then comment on the breadth of evidence for
      the use of progesterone in each neurologic disease family. Finally, we provide
      support for further human studies using progesterone to treat several neurologic
      diseases. 

PMID- 23872218
TI  - Functional characterization of SNPs in CHRNA3/B4 intergenic region associated
      with drug behaviors.
AB  - The cluster of human neuronal nicotinic receptor genes (CHRNA5/A3/B4) (15q25.1)
      has been associated with a variety of smoking and drug-related behaviors, as well
      as risk for lung cancer. CHRNA3/B4 intergenic single nucleotide polymorphisms
      (SNPs) rs1948 and rs8023462 have been associated with early initiation of alcohol
      and tobacco use, and rs6495309 has been associated with nicotine dependence and
      risk for lung cancer. An in vitro luciferase expression assay was used to
      determine whether these SNPs and surrounding sequences contribute to differences
      in gene expression using cell lines either expressing proteins characteristic of
      neuronal tissue or derived from lung cancers. Electrophoretic mobility shift
      assays (EMSAs) were performed to investigate whether nuclear proteins from these
      cell lines bind SNP alleles differentially. Results from expression assays were
      dependent on cell culture type and haplotype. EMSAs indicated that rs8023462 and
      rs6495309 bind nuclear proteins in an allele-specific way. Additionally, GATA
      transcription factors appeared to bind rs8023462 only when the minor/risk allele
      was present. Much work has been done to describe the rat Chrnb4/a3 intergenic
      region, but few studies have examined the human intergenic region effects on
      expression; therefore, these studies greatly aid human genetic research as it
      relates to observed nicotine phenotypes, lung cancer risk and potential
      underlying genetic mechanisms. Data from these experiments support the hypothesis
      that SNPs associated with human addiction-related phenotypes and lung cancer risk
      can affect gene expression, and are potential therapeutic targets. Additionally,
      this is the first evidence that rs8023462 interacts with GATA transcription
      factors to influence gene expression. 

PMID- 23872220
TI  - Adolescent exposure to Bisphenol-A increases anxiety and sucrose preference but
      impairs spatial memory in rats independent of sex.
AB  - The endocrine disruptor Bisphenol-A (BPA) has been shown to modulate estrogenic,
      androgenic, and anti-androgenic effects. The effects of BPA exposure during early
      organizational periods of development have been well documented. The current
      study focuses on the effects of short term, low-dose BPA exposure on anxiety,
      spatial memory and sucrose preference in adolescent rats. Seven week old Sprague
      Dawley rats (n=18 male, n=18 female) received daily subcutaneous injections (40
      ug/kg body weight) of BPA or vehicle for 12 days. Starting on day 6 of
      injections, subjects were tested on the elevated plus maze which provides a
      measure of anxiety, the open field test which provides a measure of anxiety and
      locomotor activity, and object placement, a measure of spatial memory. On the
      twelfth day of BPA administration, sucrose preference was tested using a standard
      two-bottle choice (tap versus sucrose solution). All rats gained weight during
      the study; there was a main effect of sex, but not BPA treatment on body weight.
      The results indicate that BPA exposure, regardless of sex, increased anxiety on
      both the elevated plus maze and open field. Spatial memory was impaired on the
      object recognition task with BPA animals spending significant less time with the
      object in the novel location than controls. Finally, a significant increase in
      sucrose consumption for both male and female subjects exposed to BPA was
      observed. The current data shows that short term BPA exposure, below the current
      reference safe daily limit of 50 ug/kg day set by the United States Environmental
      Protection Agency, during adolescent development increases anxiety, impairs
      spatial memory, and increases sucrose consumption independent of sex.

PMID- 23872221
TI  - Resistance exercise and the mechanisms of muscle mass regulation in humans: acute
      effects on muscle protein turnover and the gaps in our understanding of chronic
      resistance exercise training adaptation.
AB  - Increasing muscle mass is important when attempting to maximize sports
      performance and achieve physique augmentation. However, the preservation of
      muscle mass is essential to maintaining mobility and quality of life with aging,
      and also impacts on our capacity to recover from illness. Nevertheless, our
      understanding of the processes that regulate muscle mass in humans during
      resistance exercise training, chronic disuse and rehabilitation training
      following atrophy remains very unclear. Here, we report on some of the recent
      developments in the study of those processes thought to be responsible for
      governing human muscle protein turnover in response to intense physical activity.
      Specifically, the effects of acute and chronic resistance exercise in healthy
      volunteers and also in response to rehabilitation resistance exercise training
      following muscle atrophy will be discussed, with discrepancies and gaps in our
      understanding highlighted. In particular, ubiquitin-proteasome mediated muscle
      proteolysis (Muscle Atrophy F-box/Atrogin-1 and Muscle RING Finger 1),
      translation initiation of muscle protein synthesis (mammalian target of rapamycin
      signaling), and satellite cell mediated myogenesis are highlighted as pathways of
      special relevance to muscle protein metabolism in response to acute resistance
      exercise. Furthermore, research focused on quantifying signaling and molecular
      events that modulate muscle protein synthesis and protein degradation under
      conditions of chronic resistance training is highlighted as being urgently needed
      to improve knowledge gaps. These studies need to include multiple time-point
      measurements over the course of any training intervention and must include
      dynamic measurements of muscle protein synthesis and degradation and sensitive
      measures of muscle mass. This article is part of a Directed Issue entitled
      Molecular basis of muscle wasting. 

PMID- 23872223
TI  - Nodularins in poisoning.
AB  - Nodularins are an important class of hepatotoxic cyclic pentapeptides that are
      produced by the cyanobacteria Nodularia spumigena. These peptides have been found
      worldwide and have been implicated in the deaths of animals as well as a potent
      cyanotoxin in humans. To date, approximately 10 variants have been discovered,
      among which nodularin-R is the most abundant. Though the mechanisms of their
      potential hepatotoxicity and carcinogenicity are not well understood, the most
      frequently proposed mechanisms are described here. Most importantly, a
      comprehensive review of nodularins in poisoning is presented, including their
      bioaccumulation in water, cyanobacterial blooms and aquatic animals, the IC50,
      LC50 and LD50 values determined in laboratories, and wild, domestic and
      laboratory animal cases. However, the hazard of these toxins to humans has not
      been fully elucidated, predominantly due to the lack of exposure data. One of
      reasons underlying is that most current methods are ill suited for clinical
      monitoring. Thus, the available assays for the detection and quantification of
      nodularins are described with an emphasis on the problems encountered with each
      assay. Our ultimate aim is to demonstrate the urgency of better understanding the
      toxicity of nodularins, especially in humans, and thus effectively protecting
      ourselves from their poisoning. 

PMID- 23872222
TI  - A randomized phase II trial of fludarabine/melphalan 100 versus
      fludarabine/melphalan 140 followed by allogeneic hematopoietic stem cell
      transplantation for patients with multiple myeloma.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially
      curative treatment for multiple myeloma (MM); however, because of high treatment
      related mortality (TRM), its role is not well defined. Patients with newly
      diagnosed, relapsed, or primary refractory myeloma were enrolled in a randomized
      phase II trial of 2 reduced-intensity conditioning regimens: fludarabine 120
      mg/m(2) + melphalan 100 mg/m(2) (FM100) versus fludarabine 120 mg/m(2) +
      melphalan 140 mg/m(2) (FM140) before allo-HCT from related or unrelated donors.
      Fifty patients underwent allo-HCT using FM100 (n = 23) or FM140 (n = 27)
      conditioning between April 2002 and 2011. There were no significant differences
      between FM100 and FM140 in time to neutrophil engraftment (P = .21), acute grade
      II to IV graft-versus-host disease (GVHD) (P = 1.0), chronic GVHD (P = .24),
      response rate (P = 1.0), TRM (13% versus 15%, P = 1.0), median progression-free
      survival (PFS), 11.7 versus 8.4 months, P = .12, and median overall survival
      (OS), 35.1 versus 19.7 months, P = .38. Cumulative incidence of disease
      progression in FM100 and FM140 was 43% and 70%, respectively (P = .08). Recurrent
      disease was the most common cause of death for both FM100 (26%) and FM140 (44%),
      P = .24. On multivariate analysis, disease status at allo-HCT, complete response
      or very good partial response (VGPR) was significantly associated with longer PFS
      (15.6 versus 9.6 months in patients with <VGPR, P = .05). OS was similar across
      all variables. We conclude that FM100 and FM140 may result in similar patient
      outcomes after allo-HCT for MM.

PMID- 23872224
TI  - A physical and chemical comparison of material from a conventional spray-dried
      system and a single particle spray-dried system.
AB  - When assessing the suitability of potential drug/polymer systems for improving
      drug bioavailability, substantial efficiency gains can be achieved through the
      development and application of rapid miniaturised screening methods. For this to
      be possible new methods of small-scale formulation manufacture that produce
      materials equivalent to full-scale manufacture are urgently required. In this
      work, we use Atomic Force Microscopy (AFM) and Confocal Raman Microscopy (CRM) to
      investigate the potential physical and chemical equivalence of individually dried
      particles generated using a DRYING KINETICS ANALYZERTM (DKA) with material from a
      conventional spray-drier. For our model system of griseofulvin (at loadings of
      2.5%, w/w and 20%, w/w) and PEG 6000, the results demonstrate physicochemical
      equivalence between the two spray-drying methods for the same drug loading. Thus
      we suggest that single particle spray drying offers a viable and novel route to
      the production of materials for miniaturised methods of screening candidate
      drug/polymer formulations. 

PMID- 23872225
TI  - Effect of water on exenatide acylation in poly(lactide-co-glycolide)
      microspheres.
AB  - Peptide or protein degradation often occurs when water flows into the dosage
      form. The aim of this study was to investigate the effect of water on exenatide
      acylation in poly(lactide-co-glycolide) (PLGA) microspheres. Exenatide-loaded
      PLGA microspheres were incubated at different relative humidities (RH) as well as
      in solutions of different pH for 20 days. The stability of exenatide was
      monitored using HPLC and HPLC-MS analysis. The alteration of exenatide
      conformation caused by water was investigated by FT-IR spectroscopy. Exenatide
      and glycolide were incubated in DMSO-water solutions to verify the effect of
      exenatide conformation state on the peptide acylation. Exenatide was relatively
      stable in microspheres at lower RH, and the absorbed water could act as a
      plasticizer and thus promote the peptide acylation by PLGA. However, when the
      microspheres were incubated at 100% RH, the excessively absorbed water could
      cause conformation recovery of exenatide and play an inhibitory effect on
      acylation. The formation of acylated exenatide incubated in acetate buffer saline
      of pH 6.0 was more than that of pH 4.5 and 3.0. Stability studies of exenatide in
      glycolide solutions showed that exenatide in nonnative monomer state was easier
      to be acylated by eletrophiles than that in aggregation state. 

PMID- 23872226
TI  - Consolidation trend design based on Young's modulus of clarithromycin single
      crystals.
AB  - The key aim of this study was to determine single mechanical properties of
      clarithromycin polymorphic forms in order to select some of them as more suitable
      for the tableting process. For this purpose, AFM single-point nanoindentation was
      used. The Young's moduli of clarithromycin polymorphs were substantially
      different, which was consistent with the structural variations in their packing
      motifs. The presence of the adjacent layers, which can easily slide over each
      other due to the low energy barrier (the lowest Young's modulus was 0.25 GPa)
      resulted in better bulk compressibility (the highest Heckel coefficient) of
      clarithromycin Form I. We also addressed the importance of tip geometry screening
      because the stress during the force mode often results in tip apex fracture. Even
      the initial manufacture of the diamond-coated tips can result in defects such as
      double-apex tips.

PMID- 23872227
TI  - II. Technological approaches to improve the dissolution behavior of nateglinide,
      a lipophilic insoluble drug: co-milling.
AB  - Nateglinide is an oral antidiabetic agent that should be administered 10-30 min
      before the meal, but it shows low and pH-dependent solubility that may reduce its
      oral bioavailability. To improve nateglinide dissolution rate, the active was co
      milled with three different super-disintegrants or with some hydrophilic
      excipients, in 1:1, 1:2, and 1:4 drug to carrier ratio (w:w). The three super
      disintegrants were crosslinked polyvinylpyrrolidone (PVPC), sodium starch
      glycolate (SSG) and crosslinked carboxymethyl cellulose (CMCC). The three
      hydrophilic excipient were amorphous silica (AS), mannitol (M) and Poloxamer
      (PO). A strong enhancement of drug dissolution rate was obtained from the
      nateglinide:super-disintegrant co-milled systems in 1:4 ratio, which can be
      explained by a combination of several factors: an increase in wettability, due to
      the hydrophilic nature of the carriers, a possible reduction of particle size and
      a more intimate dispersion of the drug onto the carrier, as a result of the
      mechanical treatment.

PMID- 23872228
TI  - Health threat increases attentional bias for negative stimuli.
AB  - BACKGROUND AND OBJECTIVES: Although there is some evidence that health anxiety is
      associated with attentional bias, relatively little research has examined the
      role of situational threat on bias. This study examined the effect of health
      threat on attentional bias for negative health words. METHODS: Participants
      completed questionnaires and were then randomized to receive either threatening
      or reassuring health-related feedback. Following randomization, participants
      completed the emotional Stroop and dot-probe tasks in a counter-balanced order.
      RESULTS: On the emotional Stroop task, all participants took longer to name the
      colour of negative words, as compared to positive and neutral words. However on
      the dot probe task, differences in attentional bias emerged based on feedback
      condition. Those receiving reassuring feedback displayed a bias away from
      negative words while those receiving threatening feedback did not display a bias
      either towards or away from negative words. Following reassuring feedback only,
      metacognitions were negatively correlated with attention towards positive health
      related stimuli, suggesting another avenue for future research. CONCLUSIONS:
      Health threats lead to an increase in the processing of negative information, and
      the effect of metacognitions on processing appears to be apparent only in the
      absence of health threat.

PMID- 23872229
TI  - Gig1 and Gig2 homologs (CiGig1 and CiGig2) from grass carp (Ctenopharyngodon
      idella) display good antiviral activities in an IFN-independent pathway.
AB  - The virus-induced genes, Gig1 and Gig2, were identified first as IFN-stimulated
      genes (ISGs) from CAB cells. Previous studies suggested that Gig protein may have
      some potential antiviral functions. In this study, we cloned and identified the
      full-length cDNA sequences of Gig1 and Gig2 homologs (designated as CiGig1 and
      CiGig2, respectively) from grass carp (Ctenopharyngodon idella). The complete
      cDNA sequences of Gig1 and Gig2 contain 1231 bp and 690 bp, encoding for a 194
      amino acid protein and a 158 amino acid protein, respectively. Their structure
      characteristics of CiGig1 and CiGig2 are highly similar to the corresponding
      homologues in crucian carp. The tissue-specific expressions of CiGig1 and CiGig2
      in liver, spleen, kidney, intestine, gill and heart were significantly up
      regulated following GCHV challenge. The results indicated that CiGig1 and CiGig2
      may be involved in the antiviral immune responses in cells. To better understand
      the antiviral functions of CiGig1 and CiGig2 in vivo, CiGig1 or CiGig2 ORF cDNA
      were inserted into the plasmid pcDNA3.1, respectively. Subsequently, the
      recombinant plasmids were transfected into C. idellus kidney (CIK) cells. The
      over-expressions of CiGig1 and CiGig2 were observed in the CIK cells after
      treatment with GCHV. Cells with pcDNA3.1-CiGig1 or pcDNA-CiGig2 exhibited a
      relatively higher survival rate of (70.84% or 69.24%) than non-transfection
      (22.16%) and mock-vehicle controls (24.38%) following the virus infection. Our
      data showed that both CiGig1 and CiGig2 could exert antiviral effects effectively
      in vivo. Cycloheximide blocking protein synthesis demonstrated that both CiGig1
      and CiGig2 mRNA expression could be induced by GCHV rather than by recombinant
      grass carp IFN (rCiIFN) directly, suggesting that CiGig1 and CiGig2 may not be
      IFN-stimulated genes since they display their antivirus activities in an IFN
      independent pathway.

PMID- 23872230
TI  - Immunity against selected piscine flagellates.
AB  - This discussion is on immune response to Amyloodinium ocellatum, Cryptobia
      salmositica, Trypanoplasma borreli and Trypanosoma carassii. Piscidin and histone
      like proteins enhance innate resistance to Amyloodinium. Fish that are naturally
      resistant to Cryptobia and Trypanoplasma can be bred. Cryptobia resistance in
      charr is controlled by a dominant Mendelian locus and protection is via the
      Alternative Pathway of Complement Activation. Studies on Cryptobia-tolerant charr
      may lead to production of transgenic Cryptobia-tolerant salmon. Innate response
      to T. borreli is associated with NO in macrophages. Transferrin regulates
      resistance and carp have been bred for transferrin genotypes. Recovered fish are
      protected from homologous challenge, and complement fixing antibodies are crucial
      in protection. Studies on antigens in T. carassii may lead to a vaccine. There
      are two vaccines against cryptobiosis; a single dose of the attenuated vaccine
      protects salmonids. On challenge fish inoculated with the metalloprotease-DNA
      vaccine do not have the disease and they recover faster. 

PMID- 23872231
TI  - The Atlantic salmon protein tyrosine kinase Tyk2: molecular cloning, modulation
      of expression and function.
AB  - Tyk2, a member of the Janus Kinase (JAK) family of protein tyrosine kinases, is
      required for interferon-alpha/beta binding and signaling in higher vertebrates.
      Currently, little is known about the role of the different JAKs in signaling
      responses to interferon (IFN) in lower vertebrates including fish. In this paper
      we report the identification and characterization of Atlantic salmon (Salmo
      salar) Tyk2. Four cDNA sequences, two containing an open reading frame encoding
      full-length Tyk protein and two with an up-stream in frame stop codon, were
      identified. The deduced amino acid sequences of the salmon full-length Tyk2
      proteins showed highest identity with Tyk2 from other species and their
      transcripts were ubiquitously expressed. Like in mammals the presented data
      suggests that salmon Tyk2 is auto-phosporylated when ectopically expressed in
      cells. In our experiments, full-length salmon Tyk2 overexpressed in CHSE-cells
      phosphorylated itself, while both a kinase-deficient mutant and the truncated
      Tyk2 (Tyk-short) were inactive. Interestingly, the overexpression of full length
      Tyk2 was shown to up-regulate the transcript levels of the IFN induced gene Mx,
      thus indicating the involvement of salmon Tyk2 in the salmon IFN I pathway. 

PMID- 23872232
TI  - Proopiomelanocortin gene polymorphisms and its association with meat quality
      traits by ultrasound measurement in Chinese cattle.
AB  - Ultrasound technology was used to measure live animal meat traits instead of true
      carcass meat traits for beef production and cattle breeding by an increasing
      number of institutions. In this study, we analyzed the association between
      genetic polymorphisms of proopiomelanocortin (POMC) and ultrasound measurement
      traits in Chinese cattle. Using direct DNA sequencing in 322 individuals of 7
      different cattle subpopulation, 7 SNPs were identified for genotyping within
      790bp region of intron 2 and exon 3 of POMC. 6586 T>G in intron 2 and 6769 C>T
      and 7216 C>T in exon 3 were significantly associated with ultrasound backfat
      thickness (UBF) (P<0.05) and ultrasound loin muscle area (ULMA) (P<0.01) in the
      total population; 6694 C>T, 6706 T>C, 6796 C>T and 6810 C>T in exon 3 were
      significantly associated with ULMA (P<0.0001) in the total population. These
      results clearly suggest that these SNPs of POMC be benefit for selection of
      individuals with good quality meat in Chinese cattle breeding program. Following
      validation in other populations and breeds, these markers could be incorporated
      into breeding programs to increase the rate of improvement in carcass and meat
      quality traits.

PMID- 23872233
TI  - The relationship between the presence of ADHD and certain candidate gene
      polymorphisms in a Turkish sample.
AB  - Due to the high heritability of attention-deficit hyperactivity disorder (ADHD),
      parents of children with ADHD appear to represent a good sample group for
      investigating the genetics of the disorder. The aim of this study was to
      investigate the association between ADHD and six polymorphisms in five candidate
      genes [5-HT2A (rs6311), NET1 (rs2242447), COMT (rs4818), NTF3 (rs6332), SNAP-25
      (rs3746544) and (rs1051312)]. We included 228 parents of children diagnosed with
      ADHD and 109 healthy parents as the control group. The polymorphisms were
      genotyped using polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP) assays and analyzed using the chi-square test and the
      multinomial logit model. SNAP-25 (rs3746544) polymorphism was associated with
      loading for ADHD, while 5-HT2A (rs6311) and NET1 (rs2242447) polymorphisms were
      associated with ADHD. On the other hand, there was no significant association
      between the SNAP-25 (rs1051312), NTF3 (rs6332), or COMT (rs4818) gene
      polymorphisms and ADHD. In addition, we found that even if variation in the SNAP
      25 gene alone does not affect the phenotype, it may nevertheless lead to the
      emergence of a clinical ADHD picture in the presence of other genetic factors.
      Our findings suggest that a combination of NET1 (rs2242447) and SNAP-25
      (rs3746544) is a risk factor for ADHD. Problems associated with the noradrenergic
      and serotonergic systems and SNAP-25 may play a role, both alone and in
      interaction with one another, in the pathophysiological mechanisms of ADHD.

PMID- 23872234
TI  - Neanderthal and Denisova genetic affinities with contemporary humans:
      introgression versus common ancestral polymorphisms.
AB  - Analyses of the genetic relationships among modern humans, Neanderthals and
      Denisovans have suggested that 1-4% of the non-Sub-Saharan African gene pool may
      be Neanderthal derived, while 6-8% of the Melanesian gene pool may be the product
      of admixture between the Denisovans and the direct ancestors of Melanesians. In
      the present study, we analyzed single nucleotide polymorphism (SNP) diversity
      among a worldwide collection of contemporary human populations with respect to
      the genetic constitution of these two archaic hominins and Pan troglodytes
      (chimpanzee). We partitioned SNPs into subsets, including those that are derived
      in both archaic lineages, those that are ancestral in both archaic lineages and
      those that are only derived in one archaic lineage. By doing this, we have
      conducted separate examinations of subsets of mutations with higher probabilities
      of divergent phylogenetic origins. While previous investigations have excluded
      SNPs from common ancestors in principal component analyses, we included common
      ancestral SNPs in our analyses to visualize the relative placement of the
      Neanderthal and Denisova among human populations. To assess the genetic
      similarities among the various hominin lineages, we performed genetic structure
      analyses to provide a comparison of genetic patterns found within contemporary
      human genomes that may have archaic or common ancestral roots. Our results
      indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the
      average European gene pool, which clinally diminishes with distance from Europe.
      Our results suggest that Neanderthal genetic associations with contemporary non
      Sub-Saharan African populations, as well as the genetic affinities observed
      between Denisovans and Melanesians most likely result from the retention of
      ancient mutations in these populations.

PMID- 23872235
TI  - SP8 regulates signaling centers during craniofacial development.
AB  - Much of the bone, cartilage and smooth muscle of the vertebrate face is derived
      from neural crest (NC) cells. During craniofacial development, the anterior
      neural ridge (ANR) and olfactory pit (OP) signaling centers are responsible for
      driving the outgrowth, survival, and differentiation of NC populated facial
      prominences, primarily via FGF. While much is known about the functional
      importance of signaling centers, relatively little is understood of how these
      signaling centers are made and maintained. In this report we describe a dramatic
      craniofacial malformation in mice mutant for the zinc finger transcription factor
      gene Sp8. At E14.5 they show facial prominences that are reduced in size and
      underdeveloped, giving an almost faceless phenotype. At later times they show
      severe midline defects, excencephaly, hyperterlorism, cleft palate, and a
      striking loss of many NC and paraxial mesoderm derived cranial bones. Sp8
      expression was primarily restricted to the ANR and OP regions during craniofacial
      development. Analysis of an extensive series of conditional Sp8 mutants confirmed
      the critical role of Sp8 in signaling centers, and not directly in the NC and
      paraxial mesoderm cells. The NC cells of the Sp8 mutants showed increased levels
      of apoptosis and decreased cell proliferation, thereby explaining the reduced
      sizes of the facial prominences. Perturbed gene expression in the Sp8 mutants was
      examined by laser capture microdissection coupled with microarrays, as well as in
      situ hybridization and immunostaining. The most dramatic differences included
      striking reductions in Fgf8 and Fgf17 expression in the ANR and OP signaling
      centers. We were also able to achieve genetic and pharmaceutical partial rescue
      of the Sp8 mutant phenotype by reducing Sonic Hedgehog (SHH) signaling. These
      results show that Sp8 primarily functions to promote Fgf expression in the ANR
      and OP signaling centers that drive the survival, proliferation, and
      differentiation of the NC and paraxial mesoderm that make the face. 

PMID- 23872236
TI  - Postembryonic lineages of the Drosophila brain: II. Identification of lineage
      projection patterns based on MARCM clones.
AB  - The Drosophila central brain is largely composed of lineages, units of sibling
      neurons derived from a single progenitor cell or neuroblast. During the early
      embryonic period, neuroblasts generate the primary neurons that constitute the
      larval brain. Neuroblasts reactivate in the larva, adding to their lineages a
      large number of secondary neurons which, according to previous studies in which
      selected lineages were labeled by stably expressed markers, differentiate during
      metamorphosis, sending terminal axonal and dendritic branches into defined
      volumes of the brain neuropil. We call the overall projection pattern of neurons
      forming a given lineage the "projection envelope" of that lineage. By inducing
      MARCM clones at the early larval stage, we labeled the secondary progeny of each
      neuroblast. For the supraesophageal ganglion excluding mushroom body (the part of
      the brain investigated in the present work) we obtained 81 different types of
      clones. Based on the trajectory of their secondary axon tracts (described in the
      accompanying paper, Lovick et al., 2013), we assigned these clones to specific
      lineages defined in the larva. Since a labeled clone reveals all aspects (cell
      bodies, axon tracts, terminal arborization) of a lineage, we were able to
      describe projection envelopes for all secondary lineages of the supraesophageal
      ganglion. This work provides a framework by which the secondary neurons (forming
      the vast majority of adult brain neurons) can be assigned to genetically and
      developmentally defined groups. It also represents a step towards the goal to
      establish, for each lineage, the link between its mature anatomical and
      functional phenotype, and the genetic make-up of the neuroblast it descends from.

PMID- 23872237
TI  - Inflammation is an independent risk factor for colonic neoplasia in patients with
      ulcerative colitis: a case-control study.
AB  - BACKGROUND & AIMS: An association between inflammatory activity and colorectal
      neoplasia (CRN) has been documented in patients with ulcerative colitis (UC).
      However, previous studies did not address the duration of inflammation or the
      effects of therapy on risk for CRN. We investigated the effects of inflammation,
      therapies, and characteristics of patients with UC on their risk for CRN.
      METHODS: We collected data from 141 patients with UC without CRN (controls) and
      59 matched patients with UC who developed CRN (cases), comparing disease extent
      and duration and patients' ages. We used a new 6-point histologic inflammatory
      activity (HIA) scale to score biopsy fragments (n = 4449). Information on
      medications, smoking status, primary sclerosing cholangitis, and family history
      of CRN were collected from the University of Chicago Inflammatory Bowel Disease
      Endoscopy Database. Relationships between HIA, clinical features, and CRN were
      assessed by conditional logistic regression. RESULTS: Cases and controls were
      similar in numbers of procedures and biopsies, exposure to steroids or
      mesalamine, smoking status, and family history of CRN. They differed in
      proportion of men vs women, exposure to immune modulators, and primary sclerosing
      cholangitis prevalence. In univariate analysis, HIA was positively associated
      with CRN (odds ratio [OR], 2.56 per unit increase; P = .001), whereas immune
      modulators (including azathioprine, 6-mercaptopurine, and methotrexate) reduced
      the risk for CRN (OR, 0.35; P < .01). HIA was also associated with CRN in
      multivariate analysis (OR, 3.68; P = .001). CONCLUSIONS: In a case-control study,
      we associated increased inflammation with CRN in patients with UC. Use of immune
      modulators reduced the risk for CRN, indicating that these drugs have
      chemoprotective effects. On the basis of these data, we propose new stratified
      surveillance and treatment strategies to prevent and detect CRN in patients with
      UC.

PMID- 23872238
TI  - Magnifying chromoendoscopy and endoscopic ultrasonography measure invasion depth
      of early stage colorectal cancer with equal accuracy on the basis of a
      prospective trial.
AB  - BACKGROUND & AIMS: Magnifying chromoendoscopy (MC) and endoscopic ultrasonography
      (EUS) are used to estimate the depth of colorectal cancer (CRC) invasion, but it
      is not clear which procedure is more accurate. We performed a prospective study
      to compare MC and EUS. METHODS: A total of 70 patients with an early stage flat
      CRC lesion were enrolled at 6 institutions in Japan and randomly assigned to
      groups assessed by MC followed by EUS or EUS followed by MC. Results from MC and
      EUS measurements of 66 lesions were included in the final analysis. The invasion
      depth of each lesion was measured by each procedure and categorized as mucosal to
      slight submucosal (depth <1000 MUm) or deep submucosal (depth >= 1000 MUm);
      measurements were compared with the final diagnosis on the basis of the pathology
      analysis. All participating examiners achieved a mean kappa value >= 0.6 for both
      MC and EUS before this trial. RESULTS: MC and EUS each measured the depth of
      lesion invasion with 71.2% accuracy (correctly for 47 of 66 lesions). MC
      identified lesions with deep submucosal invasion with 74.2% sensitivity and 68.6%
      specificity, whereas EUS identified them with 67.7% sensitivity and 74.3%
      specificity. The differences between MC and EUS measurements did not differ
      significantly. However, MC required significantly shorter observation time than
      EUS (361.7 +/- 164.5 seconds vs 451.2 +/- 209.4 seconds, P = .002). CONCLUSIONS:
      MC and EUS are equally accurate in estimating the invasion depth of early stage
      CRC lesions. However, neither procedure has sufficient diagnostic accuracy to be
      used as the standard. University Hospital Medical Network Clinical Trials
      Registry, Number: UMIN 000005085.

PMID- 23872239
TI  - Direct-acting antiviral agents and the path to interferon independence.
AB  - Chronic infection with hepatitis C virus (HCV) is a major global health problem;
      there are approximately 120 to 130 million chronic infections worldwide. Since
      the discovery of HCV 24 years ago, there has been a relentless effort to develop
      successful antiviral therapies. Studies of interferon-alpha-based therapies have
      helped define treatment parameters, and these treatment strategies have cured a
      substantial percentage of patients. However, interferon-alpha must be injected;
      there are problems with tolerability, adherence, and incomplete response in a
      large percentage of patients. New drug candidates designed to target the virus or
      the host have recently been introduced at an unprecedented pace. In phase I-III
      studies, these agents have exceeded expectations and achieved rates of response
      previously not thought possible. We are, therefore, entering a new era of therapy
      for HCV infection and interferon independence. 

PMID- 23872240
TI  - Involuntary attention enhances identification accuracy for unmasked low contrast
      letters using non-predictive peripheral cues.
AB  - There is controversy regarding whether or not involuntary attention improves
      response accuracy at a cued location when the cue is non-predictive and if these
      cueing effects are dependent on backward masking. Various perceptual and
      decisional mechanisms of performance enhancement have been proposed, such as
      signal enhancement, noise reduction, spatial uncertainty reduction, and
      decisional processes. Herein we review a recent report of mask-dependent accuracy
      improvements with low contrast stimuli and demonstrate that the experiments
      contained stimulus artifacts whereby the cue impaired perception of low contrast
      stimuli, leading to an absence of improved response accuracy with unmasked
      stimuli. Our experiments corrected these artifacts by implementing an isoluminant
      cue and increasing its distance relative to the targets. The results demonstrate
      that cueing effects are robust for unmasked stimuli presented in the periphery,
      resolving some of the controversy concerning cueing enhancement effects from
      involuntary attention and mask dependency. Unmasked low contrast and/or short
      duration stimuli as implemented in these experiments may have a short enough
      iconic decay that the visual system functions similarly as if a mask were present
      leading to improved accuracy with a valid cue. 

PMID- 23872241
TI  - Psychophysical factors that have been applied to clinical perimetry.
AB  - Perimetry is the most common clinical diagnostic test procedure for evaluating
      the status of peripheral visual function in the management of ocular and
      neurologic diseases. This procedure has an extended history, and its design,
      implementation and interpretation is dependent on many principles that have been
      developed through visual psychophysical studies of target size, target duration,
      background adaptation level, chromatic characteristics and other stimulus
      properties (see Greve, 1973; Johnson, 1994, chap. 17, 1996, 2008, 2010, chap. 23;
      Johnson & Keltner, 1998, chap. 7; Johnson & Sample, 2002, chap. 22; Johnson &
      Wall, 2011, chap. 35; Wall & Johnson, 2005, chap. 2 for reviews). This paper will
      provide a general overview of the history of perimetry, selection of stimulus
      parameters, development of test strategies, clinical testing conditions, new
      procedures and approaches to perimetry, experimental design, analysis and
      interpretation methods, hypothesis testing, prediction and forecasting
      procedures, and other related topics. It is somewhat paradoxical that although
      there have been major advances in all of these areas that have significantly
      enhanced the utility and value of this clinical diagnostic test, the fundamental
      methodology has remained mostly unchanged for thousands of years. It is hoped
      that this overview will be of assistance to investigators and clinicians who wish
      to use or modify this diagnostic procedure for their ongoing career activities. 

PMID- 23872242
TI  - Analyses of alpha-amylase and alpha-glucosidase in the malaria vector mosquito,
      Anopheles gambiae, as receptors of Cry11Ba toxin of Bacillus thuringiensis subsp.
      jegathesan.
AB  - Bacillus thuringiensis subsp. jegathesan produces Cry11Ba crystal protein with
      high toxicity to mosquito larvae. The Cry11Ba toxicity is dependent on its
      receptors on mosquito larval midgut epithelial cells. Previously, a cadherin-like
      protein (AgCad2), aminopeptidase (AgAPN2) and alkaline phosphatase (AgALP1) were
      reported to be involved in regulation of Cry11Ba toxicity on Anopheles gambiae
      larvae. Here, the cDNAs encoding alpha-amylase (AgAmy1) and alpha-glucosidase
      (Agm3) were cloned from A. gambiae larva midgut. Both are
      glycophosphatidylinositol (GPI) anchored proteins on brush border membranes
      (BBMV). Immunohistochemistry revealed their localization on different regions of
      the larval midgut. AgAmy1 and Agm3 bound Cry11Ba with high affinity, 37.6 nM and
      21.1 nM respectively. Cry11Ba toxicity against A. gambiae larvae was neutralized
      by both AgAmy1 and Agm3. The results provide evidence that both AgAmy1 and Agm3
      function as receptors of Cry11Ba in A. gambiae. 

PMID- 23872244
TI  - A novel electroanalytical method for simultaneous detection of two
      neurotransmitter dopamine and serotonin in human serum.
AB  - BACKGROUND: Simultaneous measurement of dopamine and serotonin levels is of
      greater value because of their coexistence in biological systems. These facts
      have encouraged chemists to develop faster, simpler, and more sensitive
      techniques to meet the various demands and many works have been published
      describing the measurement of serum dopamine and serotonin concentrations using
      chemically modified electrodes. NEW METHOD: Electrochemical techniques based on
      various chemically modified electrodes have been widely explored for the single
      determination of dopamine and serotonin in vivo or in vitro. To the best of our
      knowledge, there are only limit reports on the electrochemical determination of
      dopamine and serotonin using mesoporous materials. On the other hand,
      simultaneous measurement of dopamine and serotonin concentrations on the basis of
      silica based mesoporous materials has not been reported. RESULTS: In the present
      work, the development an effective electroanalytical method for the simultaneous
      determination of dopamine and serotonin using cyclic and differential pulse
      voltammetry on the mobile crystalline material-41 functionalized by n-aminopropyl
      is described. Mobile crystalline material-41 functionalized by n-aminopropyl, a
      kind of mesoporous silica, was synthesized and then used to prepare an
      electrochemical device for simultaneous determination of dopamine and serotonin.
      A validated differential pulse voltammetry procedure was described to assay two
      neurotransmitters separately or combined in human serum. COMPARISON WITH EXISTING
      METHOD: The prepared sensor shows voltammetric responses with high sensitivity
      for dopamine and serotonin in optimal conditions, which makes it very suitable
      for simultaneous determination of these compounds.

PMID- 23872243
TI  - Prolonged sleep fragmentation of mice exacerbates febrile responses to
      lipopolysaccharide.
AB  - BACKGROUND: Sleep disruption is a frequent occurrence in modern society. Whereas
      many studies have focused on the consequences of total sleep deprivation, few
      have investigated the condition of sleep disruption. NEW METHOD: We disrupted
      sleep of mice during the light period for 9 consecutive days using an
      intermittently rotating disc. RESULTS: Electroencephalogram (EEG) data
      demonstrated that non-rapid eye movement (NREM) sleep was severely fragmented and
      REM sleep was essentially abolished during the 12h light period. During the dark
      period, when sleep was not disrupted, neither NREM sleep nor REM sleep times
      differed from control values. Analysis of the EEG revealed a trend for increased
      power in the peak frequency of the NREM EEG spectra during the dark period. The
      fragmentation protocol was not overly stressful as body weights and water
      consumption remained unchanged, and plasma corticosterone did not differ between
      mice subjected to 3 or 9 days of sleep disruption and home cage controls.
      However, mice subjected to 9 days of sleep disruption by this method responded to
      lipopolysaccharide with an exacerbated febrile response. COMPARISON WITH EXISTING
      METHODS: Existing methods to disrupt sleep of laboratory rodents often subject
      the animal to excessive locomotion, vibration, or sudden movements. This method
      does not suffer from any of these confounds. CONCLUSIONS: This study demonstrates
      that prolonged sleep disruption of mice exacerbates febrile responses to
      lipopolysaccharide. This device provides a method to determine mechanisms by
      which chronic insufficient sleep contributes to the etiology of many pathologies,
      particularly those with an inflammatory component.

PMID- 23872245
TI  - Biomarkers of occupational exposure to air pollution, inflammation and oxidative
      damage in taxi drivers.
AB  - Exposure to environmental pollutants has been recognised as a risk factor for
      cardiovascular events. 1-hydroxypyrene (1-OHP) is a biomarker of exposure to
      polycyclic aromatic hydrocarbons (PAHs) from traffic-related air pollution.
      Experimental studies indicate that PAH exposure could be associated with
      inflammation and atherogenesis. Thus, the purpose of this study was to evaluate
      whether the biomarker of PAH exposure is associated with biomarkers of
      inflammation and oxidative stress and if these effects modulate the risk of
      developing cardiovascular diseases in workers exposed to air pollution. This
      study included 60 subjects, comprising 39 taxi drivers and 21 non-occupationally
      exposed persons. Environmental PM2.5 and benzo[a]pyrene (BaP) levels, in addition
      to biomarkers of exposure and oxidative damage, were determined. Inflammatory
      cytokines (IL-1beta, IL-6, IL-10, TNF-alpha, IFN-gamma and hs-CRP) and serum
      levels of oxidised LDL (ox-LDL), auto-antibodies (ox-LDL-Ab) and homocysteine
      (Hcy) were also evaluated. PM2.5 and BaP exhibited averages of 12.4+/-6.9 MUg m(
      3) and 1.0+/-0.6 ng m(-3), respectively. Urinary 1-OHP levels were increased in
      taxi drivers compared to the non-occupationally exposed subjects (p<0.05) and
      were positively correlated with pro-inflammatory cytokines and negatively
      correlated with antioxidants. Furthermore, taxi drivers had elevated pro
      inflammatory cytokines, biomarkers of oxidative damage, and ox-LDL, ox-LDL-Ab and
      Hcy levels, although antioxidant enzymes were decreased compared to the non
      occupationally exposed subjects (p<0.05). In summary, our findings indicate that
      taxi drivers showed major exposure to pollutants, such as PAHs, in relation to
      non-occupationally exposed subjects. This finding was associated with higher
      inflammatory biomarkers and Hcy, which represent important predictors for
      cardiovascular events. These data suggest a contribution of PAHs to
      cardiovascular diseases upon occupational exposure.

PMID- 23872246
TI  - Exposure assessment for trihalomethanes in municipal drinking water and risk
      reduction strategy.
AB  - Lifetime exposure to disinfection byproducts (DBPs) in municipal water may pose
      risks to human health. Current approaches of exposure assessments use DBPs in
      cold water during showering, while warming of chlorinated water during showering
      may increase trihalomethane (THM) formation in the presence of free residual
      chlorine. Further, DBP exposure through dermal contact during showering is
      estimated using steady-state condition between the DBPs in shower water impacting
      on human skin and skin exposed to shower water. The lag times to achieve steady
      state condition between DBPs in shower water and human skin can vary in the range
      of 9.8-391.2 min, while shower duration is often less than the lag times.
      Assessment of exposure without incorporating these factors might have
      misinterpreted DBP exposure in some previous studies. In this study, exposure to
      THMs through ingestion was estimated using cold water THMs, while THM exposure
      through inhalation and dermal contact during showering was estimated using THMs
      in warm water. Inhalation of THMs was estimated using THM partition into the
      shower air, while dermal uptake was estimated by incorporating lag times (e.g.,
      unsteady and steady-state phases of exposure) during showering. Probabilistic
      approach was followed to incorporate uncertainty in the assessment. Inhalation
      and dermal contact during showering contributed 25-60% of total exposure.
      Exposure to THMs during showering can be controlled by varying shower stall
      volume, shower duration and air exchange rate following power law equations. The
      findings might be useful in understanding exposure to THMs, which can be extended
      to other volatile compounds in municipal water.

PMID- 23872247
TI  - Associations between ambient air pollution and daily mortality among elderly
      persons in Montreal, Quebec.
AB  - BACKGROUND: Persons with underlying health conditions may be at higher risk for
      the short-term effects of air pollution. We have extended our original mortality
      time series study in Montreal, Quebec, among persons 65 years of age and older,
      for an additional 10 years (1990-2003) to assess whether these associations
      persisted and to investigate new health conditions. METHODS AND RESULTS: We
      created subgroups of subjects diagnosed with major health conditions one year
      before death using billing and prescription data from the Quebec Health Insurance
      Plan. We used parametric log-linear Poisson models within the distributed lag non
      linear models framework, that were adjusted for long-term temporal trends and
      daily maximum temperature, for which we assessed associations with NO2, O3, CO,
      SO2, and particles with aerodynamic diameters 2.5 MUm in diameter or less
      (PM2.5). We found positive associations between daily non-accidental mortality
      and all air pollutants but O3 (e.g., for a cumulative effect over a 3-day lag,
      with a mean percent change (MPC) in daily mortality of 1.90% [95% confidence
      interval: 0.73, 3.08%] for an increase of the interquartile range (17.56 MUg m(
      3)) of NO2). Positive associations were found amongst persons having
      cardiovascular disease (cumulative MPC for an increase equal to the interquartile
      range of NO2=2.67%), congestive heart failure (MPC=3.46%), atrial fibrillation
      (MPC=4.21%), diabetes (MPC=3.45%), and diabetes and cardiovascular disease
      (MPC=3.50%). Associations in the warm season were also found for acute and
      chronic coronary artery disease, hypertension, and cancer. There was no
      persuasive evidence to conclude that there were seasonal associations for
      cerebrovascular disease, acute lower respiratory disease (defined within 2 months
      of death), airways disease, and diabetes and airways disease. CONCLUSIONS: These
      data indicate that individuals with certain health conditions, especially those
      with diabetes and cardiovascular disease, hypertension, atrial fibrillation, and
      cancer, may be susceptible to the short-term effects of air pollution.

PMID- 23872248
TI  - A novel passive dosing system for determining the toxicity of phenanthrene to
      early life stages of zebrafish.
AB  - Reliable experimental early life stage chronic toxicity data for fish are limited
      and further data are needed for polyaromatic hydrocarbons to establish
      environmental quality objectives and compare with toxicity model predictions.
      Efforts are underway to develop a zebrafish embryo toxicity test guideline to
      reduce, refine and replace the use of vertebrates in animal testing. An
      adaptation of this method which includes embryo lethal and sub-lethal
      developmental endpoints after a 5-day exposure as well as larval survival and
      growth endpoints during a subsequent 25-day test period is described using
      phenanthrene as a model test substance. To deliver well controlled exposure
      concentrations, a passive dosing system consisting of silicone coated vials and
      silicone O-rings was employed. Acute results indicated that edema and spinal
      curvature were the most sensitive sub-lethal effects observed and in many cases
      preceded observed mortality. The 30-day LC/EC10 for larval survival and growth
      was 40 and 67 MUg/L respectively. Concentrations shown to cause adverse effects
      in this study are in the range of previous studies that have investigated the
      chronic effects of phenanthrene on fish. Further, results indicate that predicted
      water quality objectives for phenanthrene derived using the target lipid model
      are protective of early life stage effects on zebrafish. Based on these results
      the predicted water quality objectives for phenanthrene derived using the target
      lipid model (10 MUg/L) would be protective of early life stage effects on
      zebrafish.

PMID- 23872249
TI  - Interspecific comparison of polycyclic aromatic hydrocarbons and persistent
      organochlorines bioaccumulation in bivalves from a Mediterranean coastal lagoon.
AB  - The bioaccumulation of polycyclic aromatic hydrocarbons (PAHs), organochlorine
      pesticides (OCPs) and polychlorinated biphenyls (PCBs) was characterized in
      cockle, oyster and noble pen shell from nine areas in the Mar Menor lagoon with
      different hydrodynamic and pollutant sources. Biota, sediment and water samples
      were simultaneously collected in the spring and autumn of 2010. Considering all
      bivalve samples, PAH concentrations ranged from 8.98 to 370 MUg.kg(-1) d.w.,
      those of PCBs from 0.15 to 42.36 MUg.kg(-1) d.w. and those of DDXs from below
      detection limit to 240.6 MUg.kg(-1) d.w., where p,p'-DDE was the main fraction.
      The bioaccumulation of PAHs was similar for cockle, oyster and noble pen shell,
      being higher close to ports and wastewater effluents. However, DDX and PCB
      bioaccumulations in oyster and noble pen shell were significantly higher than in
      cockle in spring (p=0.02). The first organic pollutant bioaccumulation data for
      noble pen shell were obtained in this study, showing a preferential accumulation
      of pyrene. The increase of PAH bioaccumulation in autumn, as compared to spring,
      was low, due to high water temperatures during the summer, which favoured PAH
      dissipation processes. No significant seasonal variations were detected for OCPs
      and PCBs, except in some specific areas. The PAH, PCB and OCP levels detected in
      these bivalves were lower than OSPAR/MED POL environmental assessment criteria,
      except for p,p'-DDE in bivalves sited close to El Albujon watercourse mouth.

PMID- 23872250
TI  - Silicone rubber passive samplers for measuring pore water and exchangeable
      concentrations of polycyclic aromatic hydrocarbons concentrations in sediments.
AB  - The use of a silicone rubber passive sampler for the assessment of the
      availability of lipophilic organic contaminants in sediments is described. The
      passive sampler accumulated polycyclic aromatic hydrocarbons (PAHs) from
      sediments with an equilibration time of 20 days for most PAHs. The method was
      used to measure the free dissolved concentrations in pore water of 30 PAHs
      (parent and alkylated), their water exchangeable concentrations and sediment
      water partition coefficients in field sediments from a Scottish sea loch that
      supports fish farming. Fluoranthene and pyrene dominated the PAH concentration
      composition in the pore waters. The water exchangeable concentration reflected
      the pyrogenic pollution pattern found in the sediments and indicated that a
      proportion of the PAHs were not available for exchange with the aqueous phase.
      Strong linear relationships between organic carbon normalised sediment-water
      partition coefficients (logK(oc)) and corresponding octanol-water partition
      coefficients of PAHs were obtained. The logK(oc) values obtained are on average,
      0.6 log units higher than literature values commonly used in sediment risk
      assessments, consequently direct measurements of logK(oc) in field sediments
      should be used to improve the reliability of risk assessments.

PMID- 23872251
TI  - The spatial and temporal association of neighborhood drug markets and rates of
      sexually transmitted infections in an urban setting.
AB  - This study examined temporal and spatial relationships between neighborhood drug
      markets and gonorrhea among census block groups from 2002 to 2005. This was a
      spatial, longitudinal ecologic study. Poisson regression was used with adjustment
      in final models for socioeconomic status, residential stability and vacant
      housing. Increased drug market arrests were significantly associated with a 11%
      increase gonorrhea (adjusted relative risk (ARR) 1.11; 95% CI 1.05, 1.16).
      Increased drug market arrests in adjacent neighborhoods were significantly
      associated with a 27% increase in gonorrhea (ARR 1.27; 95% CI 1.16, 1.36),
      independent of focal neighborhood drug markets. Increased drug market arrests in
      the previous year in focal neighborhoods were not associated with gonorrhea (ARR
      1.04; 95% CI 0.98, 1.10), adjusting for focal and adjacent drug markets. While
      the temporal was not supported, our findings support an associative link between
      drug markets and gonorrhea. The findings suggest that drug markets and their
      associated sexual networks may extend beyond local neighborhood boundaries
      indicating the importance of including spatial lags in regression models
      investigating these associations. 

PMID- 23872252
TI  - Monoterpene bisindole alkaloids, from the African medicinal plant Tabernaemontana
      elegans, induce apoptosis in HCT116 human colon carcinoma cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tabernaemontana elegans is a medicinal plant used
      in African traditional medicine to treat several ailments including cancer. The
      aims of the present study were to identify anti-cancer compounds, namely
      apoptosis inducers, from Tabernaemontana elegans, and hence to validate its usage
      in traditional medicine. METHODS AND MATERIALS: Six alkaloids, including four
      monomeric indole (1-3, and 6) and two bisindole (4 and 5) alkaloids, were
      isolated from the methanolic extract of Tabernaemontana elegans roots. The
      structures of these compounds were characterized by 1D and 2D NMR spectroscopic
      and mass spectrometric data. Compounds 1-6 along with compound 7, previously
      isolated from the leaves of the same species, were evaluated for in vitro
      cytotoxicity against HCT116 human colon carcinoma cells by the MTS metabolism
      assay. The cytotoxicity of the most promising compounds was corroborated by Guava
      ViaCount flow cytometry assays. Selected compounds were next studied for
      apoptosis induction activity in HCT116 cells, by evaluation of nuclear morphology
      following Hoechst staining, and by caspase-3 like activity assays. RESULTS: Among
      the tested compounds (1-7), the bisindole alkaloids tabernaelegantine C (4) and
      tabernaelegantinine B (5) were found to be cytotoxic to HCT116 cells at 20 uM,
      with compound 5 being more cytotoxic than the positive control 5-Fluorouracil (5
      FU), at a similar dose. In fact, even at 0.5 uM, compound 5 was more potent than
      5-FU. Compounds 4 and 5 induced characteristic patterns of apoptosis in HCT116
      cancer cells including, cell shrinkage, condensation, fragmentation of the
      nucleus, blebbing of the plasma membrane and chromatin condensation. Further,
      general caspase-3-like activity was increased in cells exposed to compounds 4 and
      5, corroborating the nuclear morphology evaluation assays. CONCLUSIONS: Bisindole
      alkaloids tabernaelegantine C (4) and tabernaelegantinine B (5) were
      characterized as potent apoptosis inducers in HCT116 human colon carcinoma cells
      and as possible lead/scaffolds for the development of anti-cancer drugs. This
      study substantiates the usage of Tabernaemontana elegans in traditional medicine
      to treat cancer.

PMID- 23872253
TI  - Wen Luo Yin inhibits angiogenesis in collagen-induced arthritis rat model and in
      vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Wen Luo Yin (WLY) is a
      traditional Chinese formula, which has the traditional use of scattering cold
      pathogen, draining dampness, freeing the flow of network vessels and relieving
      pains. It is extensively used in the treatment of rheumatoid arthritis (RA)
      patients for more than 2000 years, but its actions on angiogenesis of RA have not
      been clarified. The present study aims to determine the anti-angiogenic activity
      of WLY on collagen-induced arthritis (CIA) rat model and in human fibroblast-like
      synoviocytes of RA (HFLS-RA) and human umbilical vein endothelial cells (HUVEC).
      MATERIALS AND METHODS: For in vivo experiment, arthritis was induced by
      immunization with bovine II collagen in DA rats. Treatment with WLY (3.45, 6.9,
      13.8 g/kg, p.o., daily), or vehicle began from day 1 to day 28 of first
      immunization. The arthritis score, arthritis incidence, microfocal computed
      tomography analysis and histopathology evaluation of inflamed joints were
      assessed. Angiogenesis was measured by synovial vessel density with
      immunohistochemistry and histomorphometric analysis in synovial membrane tissues
      of joints. For in vitro experiments, HFLS-RA and HUVEC were used. Assays to
      determine HFLS-RA migration and adhesion were performed in the presence of
      vascular endothelial growth factor (VEGF)165 or interleukin (IL)-1beta and/or the
      WLY (8, 16, 32 mg/ml). Angiogenesis was assessed by measuring the migration,
      adhesion, and tube formation of HUVEC. Further the effect of treatment with WLY
      on expression levels of angiogenic activators in sera of CIA rats and in IL-1beta
      induced HFLS-RA were evaluated by enzyme linked immunosorbent assay. RESULTS: WLY
      significantly decreased the arthritis score and arthritis incidence, and
      inhibited inflammation, pannus formation, cartilage and bone destruction of
      inflamed joints in CIA rats. More interestingly, doses of 3.45-13.8 g/kg WLY
      could markedly reduce the capillaries, small, medium and large vessel density in
      synovial membrane tissues of inflamed joints. Moreover, WLY suppressed the VEGF
      induced chemotactic migration of HFLS-RA and HUVEC, and inhibited matrigel
      induced cell adhesion of them. It also disrupted tube formation of HUVEC on
      matrigel. Furthermore, WLY significantly reduced the expression of angiogenic
      activators including tumor necrosis factor-alpha, IL-1beta, IL-17, VEGF, VEGFR,
      angiopoietin (Ang)-1, Ang-2 and Ang-2 receptor in sera of CIA rats and/or in IL
      1beta-induced HFLS-RA/HUVEC. CONCLUSIONS: Our data suggest for the first time
      that WLY posses the anti-angiogenic effect in RA both in vivo and in vitro by
      downregulating angiogenic activators.

PMID- 23872254
TI  - Effects of red ginseng extract on sleeping behaviors in human volunteers.
AB  - ETHNOPHARMACOLOGICAL RELEVENCE: The ginseng root has been traditionally used as a
      sedative in oriental countries. However, the condition "ginseng abuse syndrome"
      (GAS), defined as hypertension, nervousness, sleeplessness, skin eruption, and
      morning diarrhea, was coined as a result of a study of people who had been using
      a variety of ginseng preparations. However, we reported that administration of
      RGE increased rapid eye movement (REM) and non rapid eye movement (NREM) sleep
      via GABAergic systems in animals. Therefore, this study was performed to
      investigate how red ginseng extract (RGE) affects sleeping behaviors in human
      volunteers. MATERIALS AND METHODS: RGE (1500 mg) was orally administered to young
      male healthy volunteers (from 15 to 37 years old ages, n=15) three times a day
      for 7 days. Overnight polysomnographic (PSG) studies were performed two times, 1
      day before and 7 days after RGE administration. We investigated differences in
      sleep architecture parameters such as total sleep time (TST), sleep efficacy (SE:
      total sleep time/time in bed), proportion of each sleep stage, and wakefulness
      after sleep onset (WASO) between baseline PSG and PSG after RGE administration.
      RESULTS: Total wake time (TWT) was significantly reduced (P<0.05) and SE was
      increased (P<0.05), although slow wave sleep stage 1 (N1) was reduced (P<0.01)
      and non-rapid eye movement (REM) sleep was increased (P<0.03) after
      administration. CONCLUSION: From these results, it is presumed that RGE intake
      would improve the quality of sleep, thus having beneficial effects on sleep
      disturbed subjects.

PMID- 23872256
TI  - Evaluation of the anti-inflammatory activity of riparin II (O-methil-N-2-hidroxi
      benzoyl tyramine) in animal models.
AB  - Riparin II (RipII), an alkamide isolated from the green fruit of Aniba riparia,
      was tested in the various animal models of inflammation to investigate its anti
      inflammatory activity. Male Wistar rats (180-240g) were treated with RipII by
      gavage at doses 25 or 50mg/kg, before initiating the inflammatory responses. The
      tests used were paw edema induced by carrageenan, dextran, histamine or
      serotonin; peritonitis induced by carrageenan and fMLP, as well as the
      measurement of MPO activity, TNF-alpha and Il-1beta amount in the peritoneal
      fluid. In the animal models of carrageenan and dextran-induced paw edema, the
      animals treated with RipII showed lower edema than those of the control group.
      Treatment with RipII also reduced the paw edema induced by histamine but not
      serotonin. In the carrageenan-induced peritonitis model, treatment with RipII
      reduced leukocyte migration, the MPO activity and the amount of TNF-alpha and IL
      1beta in the peritoneal fluid. In summary, these results indicate that RipII has
      an anti-inflammatory activity in chemical models of acute inflammation. RipII
      might be directly or indirectly inhibiting the activity, production or release of
      pro-inflammatory mediators involved in the generation of the pain associated with
      inflammation. 

PMID- 23872255
TI  - Antioxidant, metal-binding and DNA-damaging properties of flavonolignans: a joint
      experimental and computational highlight based on 7-O-galloylsilybin.
AB  - Besides the well-known chemoprotective effects of polyphenols, their prooxidant
      activities via interactions with biomacromolecules as DNA and proteins are of the
      utmost importance. Current research focuses not only on natural polyphenols but
      also on synthetically prepared analogs with promising biological activities. In
      the present study, the antioxidant and prooxidant properties of a semi-synthetic
      flavonolignan 7-O-galloylsilybin (7-GSB) are described. The presence of the
      galloyl moiety significantly enhances the antioxidant capacity of 7-GSB compared
      to that of silybin (SB). These findings were supported by electrochemistry, DPPH
      (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, total antioxidant capacity
      (CL-TAC) and DFT (density functional theory) calculations. A three-step oxidation
      mechanism of 7-GSB is proposed at pH 7.4, in which the galloyl moiety is first
      oxidized at Ep,1=+0.20V (vs. Ag/AgCl3M KCl) followed by oxidation of the 20-OH
      (Ep,2=+0.55V) and most probably 5-OH (Ep,3=+0.95V) group of SB moiety. The
      molecular orbital analysis and the calculation of O-H bond dissociation
      enthalpies (BDE) fully rationalize the electrooxidation processes. The metal
      (Cu(2+)) complexation of 7-GSB was studied, which appeared to involve both the
      galloyl moiety and the 5-OH group. The prooxidant effects of the metal-complexes
      were then studied according to their capacity to oxidatively induce DNA
      modification and cleavage. These results paved the way towards the conclusion
      that 7-O-galloyl substitution to SB concomitantly (i) enhances antioxidant (ROS
      scavenging) capacity and (ii) decreases prooxidant effect/DNA damage after Cu
      complexation. This multidisciplinary approach provides a comprehensive
      mechanistic picture of the antioxidant vs. metal-induced prooxidant effects of
      flavonolignans at the molecular level, under ex vivo conditions. 

PMID- 23872257
TI  - Improved sensitivity of point of care troponin I values using reporting to below
      99th percentile of normals. Schneider HG et al.

PMID- 23872258
TI  - The relationship between ultra-short telomeres, aging of articular cartilage and
      the development of human hip osteoarthritis.
AB  - INTRODUCTION: Ultra-short telomeres caused by stress-induced telomere shortening
      are suggested to induce chondrocyte senescence in human osteoarthritic knees.
      Here we have further investigated the role of ultra-short telomeres in the
      development of osteoarthritis (OA) and in aging of articular cartilage in human
      hips. MATERIALS AND METHODS: Cartilage was obtained from four different distances
      of the central weight-bearing area in human femoral heads (14 OA and 9 non-OA).
      Samples were split into three: one for quantification of ultra-short single
      telomeres by Universal STELA and mean telomere length measurement by Q-PCR; one
      for histological grading of OA, and one for immunohistochemical staining.
      RESULTS: Load of ultra-short telomeres increased closer to the central weight
      bearing area and correlated with cartilage degradation in both OA and non-OA
      samples. Mean telomere length decreased with decreasing distance to the central
      weight-bearing area, however, unexpectedly increased in the most central zone.
      This increase was associated with immunohistochemical findings of cells
      expressing markers characteristic of progenitor-like cells. CONCLUSION: These
      findings suggest a role of short telomeres in the development of OA and in aging
      of articular cartilage. Furthermore, progenitor-like cells with long telomeres
      may be recruited to the most damaged areas of the cartilage.

PMID- 23872259
TI  - The energy trade-off between growth and longevity.
AB  - Understanding the trade-offs between organisms' life history traits has been a
      major goal of physiology, ecology and evolution. In the last few decades, two
      types of intra-specific studies have highlighted the trade-off between growth and
      longevity. First, diet restriction (DR), as an environmental intervention, has
      been shown to suppress growth and extend the lifespan of a broad range of
      animals. Second, genetic studies have also shown that mice, whose growth hormone
      function is genetically modified (GM), grow slower and live longer than their
      wild-type siblings. Despite a wealth of empirical data, still largely missing is
      a theoretical framework that specifies and makes quantitative predictions on this
      trade-off. Here, I present a mechanistic model based on the principles of energy
      conservation. The model quantifies explicitly how DR and GM alter the animal's
      energy budget, and channel metabolic energy to somatic maintenance by suppressing
      growth, thereby extending lifespan. Data from a diverse set of empirical studies
      on small rodents supports the predictions of the model. More importantly, the
      model reveals that although DR and GM are two different methods to extend
      lifespan, i.e., environmental vs. genetic, the underlying mechanisms of them are
      the same from the energetic viewpoint. 

PMID- 23872260
TI  - GSK3beta/beta-catenin signaling is correlated with the differentiation of glioma
      cells induced by wogonin.
AB  - Malignant gliomas are the most common and most aggressive primary brain tumor,
      and for which differentiation therapy has emerged as a promising candidate
      strategy. In this study, we used in vitro and in vivo assays to examine the
      differentiation effects of wogonin, a major active constituent of Scutellaria
      baicalensis, on glioma C6 and U251 cells. We found that wogonin can suppress cell
      proliferation and induce G0/G1 arrest under a concentration-dependent manner.
      Wogonin also triggered significant reduction in the G1 cell-cycle regulatory
      proteins cyclin D1, cyclin-dependent kinase 2 and 4 along with overexpression of
      cell-cycle inhibitory proteins p27. Immunofluorescence and western blot analysis
      indicated that wogonin increased the expression of lineage-specific
      differentiation marker glial fibrillary acidic protein (GFAP). In mechanisms, we
      verified that wogonin significantly diminished the phosphorylated level of
      protein kinase B (AKT), and maintenance of low beta-catenin expression level was
      dependent on glycogen synthase kinase 3beta (GSK3beta) activation at Ser9.
      Blocking GSK3beta/beta-catenin pathway was required for wogonin-induced
      proliferation inhibition and terminal differentiation by using canonical
      activator lithium chloride (LiCl) and inhibitor dickkopf-1 (Dkk1). Moreover,
      intravenous administration of wogonin delayed the growth of C6 glioma in the
      intracranial tumor model. These findings provide the evidence and mechanistic
      support for wogonin-based differentiation therapies for malignant glioblastoma.
      Furthermore, inhibition of GSK3beta/beta-catenin pathway may be a key and
      requisite factor in glioma differentiation. 

PMID- 23872262
TI  - The simultaneous repair of an Irreducible Diaphragmatic Hernia while carrying out
      a Cesarean Section.
AB  - INTRODUCTION: Diaphragmatic hernia complicating pregnancy rarely occurs while it
      is frequently misdiagnosed. PRESENTATION OF CASE: A pregnant woman who had
      suffered from recurrent right upper-quadrant abdominal pain for 4 months was
      hospitalized near full term because the unrelieved abdominal pain was so severe
      that she couldn't lie down. Following the emergency caesarean, we found a part of
      the transverse colon and a part of omentum were trapped in the thorax through a
      3cm by 3cm laceration in the patient's diaphragm. We removed all trapped
      intestine which was about 40cm long and repaired diaphragmatic hernia at the same
      time. DISCUSSION: Radiography is useful to diagonisis diaphragmatic hernia, but
      it had little use for pregnant women. An irreducible diaphragmatic hernia
      represent a surgical emergency irrespective of fetal maturity. In our case, she
      had her hernia repaired just during caesarean section by laparotomy. CONCLUSION:
      Careful examination and a timely operation are needed to treat diaphragmatic
      hernia complicating pregnancy.

PMID- 23872261
TI  - Methylmercury exposure increases lipocalin related (lpr) and decreases activated
      in blocked unfolded protein response (abu) genes and specific miRNAs in
      Caenorhabditis elegans.
AB  - Methylmercury (MeHg) is a persistent environmental and dietary contaminant that
      causes serious adverse developmental and physiologic effects at multiple cellular
      levels. In order to understand more fully the consequences of MeHg exposure at
      the molecular level, we profiled gene and miRNA transcripts from the model
      organism Caenorhabditis elegans. Animals were exposed to MeHg (10 MUM) from
      embryo to larval 4 (L4) stage and RNAs were isolated. RNA-seq analysis on the
      Illumina platform revealed 541 genes up- and 261 genes down-regulated at a cutoff
      of 2-fold change and false discovery rate-corrected significance q < 0.05. Among
      the up-regulated genes were those previously shown to increase under oxidative
      stress conditions including hsp-16.11 (2.5-fold), gst-35 (10.1-fold), and fmo-2
      (58.5-fold). In addition, we observed up-regulation of 6 out of 7 lipocalin
      related (lpr) family genes and down regulation of 7 out of 15 activated in
      blocked unfolded protein response (abu) genes. Gene Ontology enrichment analysis
      highlighted the effect of genes related to development and organism growth. miRNA
      seq analysis revealed 6-8 fold down regulation of mir-37-3p, mir-41-5p, mir-70
      3p, and mir-75-3p. Our results demonstrate the effects of MeHg on specific
      transcripts encoding proteins in oxidative stress responses and in ER stress
      pathways. Pending confirmation of these transcript changes at protein levels,
      their association and dissociation characteristics with interaction partners, and
      integration of these signals, these findings indicate broad and dynamic
      mechanisms by which MeHg exerts its harmful effects.

PMID- 23872263
TI  - Adult right-sided Bochdalek hernia with ileo-cecal appendix: Almeida-Reis hernia.
AB  - INTRODUCTION: Bochdalek hernia is one of the most common congenital abnormalities
      manifested in infants. In the adult is a rarity, with a prevalence of 0.17-6% of
      all diaphragmatic hernias. Right-sided Bochdalek hernias containing colon are
      even more rare, with no case described in the literature with ileo-cecal
      appendix. PRESENTATION OF CASE: The authors present a case of a right-sided
      Bochdalek hernia in an adult female of 49 years old, presented with severe
      respiratory failure. During laparotomy for hernia correction, were found in an
      intrathoracic position the cecum and ileo-cecal appendix, the right colon and the
      transverse colon. DISCUSSION: Although useful in patient evaluation, clinical
      history and physical examination are not helpful in making diagnosis because of
      their nonspecific character. CT scan is the most accurate exam for making
      diagnosis. Most of the times there is no hernial sac. Surgery is the treatment of
      choice, and it is always indicated even if asymptomatic. In general suture of the
      defect is possible. Due to patient's weak respiratory function we chose
      laparotomy by Kocher incision. CONCLUSION: Being the first case of a right-sided
      Bochdalek hernia in the adult with a herniated ileo-cecal appendix, we name it
      Almeida-Reis hernia.

PMID- 23872264
TI  - Vasculitis of the bladder: An extremely rare case report.
AB  - INTRODUCTION: Isolated vasculitis of the bladder is extremely rare. The main
      causes of which are auto-immune diseases and occasionally infections.
      Corticosteroid therapy plays a central role in treatment in the majority of
      cases. PRESENTATION OF CASE: We report a case of gross hematuria associated with
      irritative low urinary tract symptoms (LUTS) and an increase of biological
      parameters of inflammation. Radiologic studies suspected a pelvic tumor process.
      We performed a cystoscopy with multiple biopsies. The pathological findings of
      the chips were in favor of a thrombotic nongranulomatous vasculitis of small and
      medium caliber. In view of these findings, all systemic diseases and inflammatory
      diseases such as cryoglobulinemia, the anti-phospholipid syndrome, Crohn's
      disease were eliminated. The symptoms regressed completely under antibiotics and
      anticoagulants. DISCUSSION: Our treatment options were based on the extent of the
      acute phase reaction and the pelvic venous thrombosis. A few similar cases have
      been reported in the literature, particularly a case of isolated necrotizing
      vasculitis of the bladder involving small vessels with a mild laboratory acute
      phase reaction which was treated with corticosteroids and cyclophosphamide.
      CONCLUSION: It is important to differentiate this rare pathological feature of
      the bladder from other bladder tumors as the treatment is medical rather than
      surgical.

PMID- 23872265
TI  - Autologous reconstruction of the inguinal ligament using pedicled fascia lata
      flap: A new technique.
AB  - INTRODUCTION: A technique of reconstructing the inguinal ligament using a
      pedicled fascia lata flap is described. PRESENTATION OF CASE: A 62-year-old man
      was referred with massive bilateral abdominal wall hernias, following numerous
      attempts at repair and subsequent recurrences. There was complete absence of the
      right inguinal ligament. The inguinal ligament was reconstructed using a strip of
      fascia lata, pedicled on the anterior superior iliac spine. This was transposed
      to cover the external iliac vessels, and sutured to the pubic tubercle. The
      musculoaponeurotic abdominal wall was reconstructed with two 20cm*20cm sheets of
      porcine acellular dermal matrix and an overlying sheet of polypropylene mesh,
      sutured to the remaining abdominal wall muscles laterally, and to both inguinal
      ligaments. The cutaneous abdominal wall was closed with an abdominoplasty
      technique. The reconstruction has remained intact nine months following surgery.
      DISCUSSION: Complete destruction of the inguinal ligament is rare but can occur
      following multiple operative procedures or trauma. To date, the only published
      reports of inguinal ligament reconstruction have been performed using synthetic
      mesh. The use of autologous tissue should reduce the risk of erosion into the
      neurovascular bundle, seroma formation, and enhance integration into surrounding
      tissues. CONCLUSION: This new technique for autologous reconstruction of the
      inguinal ligament provides a safe alternative to the use of synthetic mesh in the
      operative armamentarium of plastic and hernia surgeons.

PMID- 23872266
TI  - WITHDRAWN: Application of real time RT-PCR for the genetic homogeneity and
      stability tests of the seed candidates for live attenuated influenza vaccine
      production.
AB  - This article has been withdrawn at the request of the author and 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- 23872267
TI  - Validation of an anti-measles virus-specific IgG assay with oral fluid samples
      for immunization surveillance in Bangladesh.
AB  - Immune marker surveys may be used as substitutes or in conjunction with
      traditional surveys to monitor immunization program performance. This study
      assessed the validity and reliability of the Microimmune anti-measles virus
      specific IgG ELISA with oral fluid samples (OF-ELISA) among a random sample of
      children ages 12-16 months in Bangladesh. Up to two oral fluid samples and one
      serum sample were analyzed for the presence of protective levels of anti-measles
      IgG antibodies. Results from the OF-ELISA were compared to the Enzygnost anti
      measles IgG ELISA with serum and multivariate logistic regression models were
      developed to identify risk factors for false negative oral fluid results. Anti
      measles IgG antibodies were measured in 330 paired oral fluid and serum samples.
      Immune marker prevalence of measles IgG antibodies was significantly higher in
      serum (88.1%, 95% CI: [84.1, 91.5]) than oral fluid (56.1% [50.2, 61.5]).
      Sensitivity (60.2% [54.1, 66.0]) and specificity (75.7% [58.8, 88.2]) of the OF
      ELISA were lower than expected, but sensitivity significantly improved for
      individuals with higher anti-measles IgG in serum. False negative oral fluid
      results were associated with month of sample collection and variability between
      data collectors and assay procedures. Due to poor performance, caution should be
      exercised when using oral fluid samples to assess population immunity to measles
      virus, especially in highly vaccinated populations. 

PMID- 23872268
TI  - A nanoparticle-assisted PCR assay to improve the sensitivity for rapid detection
      and differentiation of wild-type pseudorabies virus and gene-deleted vaccine
      strains.
AB  - Nanoparticle-assisted polymerase chain reaction (nanoPCR) is a novel method for
      the rapid amplification of DNA and has been adopted for the detection of virus
      because of its simplicity, rapidity, and specificity. A nanoPCR assay was
      developed to detect and differentiate wild-type and gene-deleted pseudorabies
      virus (PRV). Three pairs of primers for nanoPCR developed in this study were
      selected from conserved regions of PRV, producing specific amplicons of 431 bp
      (gB), 316 bp (gE), and 202 bp (gG). The sensitivity of this assay using purified
      plasmid constructs containing the specific gene fragments was 100-1000 fold
      higher than conventional PCR. The PRV nanoPCR assay did not amplify porcine
      parvovirus, porcine circovirus type 2, porcine reproductive and respiratory
      syndrome virus, porcine teschovirus, or African swine fever virus but produced
      three bands of expected size with PRV and two bands of expected size with the
      gene-deleted PRV-Bartha-K61. Of 110 clinical samples collected from seven
      provinces in China, 53% and 48% were positive for wild-type PRV according to the
      nanoPCR assay and virus isolation, respectively.

PMID- 23872269
TI  - A new accurate assay for Coxsackievirus A 16 by fluorescence detection of
      isothermal RNA amplification.
AB  - Coxsackievirus A 16 (CA16) is one of the most common causes of hand, foot, and
      mouth disease (HFMD) worldwide. Without a vaccine or antiviral drug early, rapid,
      and accurate detection is critical for preventing and controlling HFMD. A
      simultaneous amplification and testing (SAT) assay was developed for detecting
      CA16 based on isothermal RNA amplification with fluorescence using standard, real
      time PCR equipment. Primers and probes were designed to target the VP1 region of
      CA16. Virus strains and clinical specimens were used to evaluate the diagnostic
      performance characteristics of the assay. The assay detected as few as 10 copies
      of CA16 RNA transcripts. Using real-time PCR plus sequencing as the reference
      standard, the sensitivity and specificity of the SAT-CA16 assay were 100% and
      99.2%, respectively. These findings indicate that SAT-CA16 is a rapid and
      reliable method for detecting CA16. 

PMID- 23872270
TI  - A single amino acid alteration in PGR5 confers resistance to antimycin A in
      cyclic electron transport around PSI.
AB  - In Arabidopsis thaliana, the main route of cyclic electron transport around PSI
      is sensitive to antimycin A, but the site of inhibition has not been clarified.
      We discovered that ferredoxin-dependent plastoquinone reduction in ruptured
      chloroplasts was less sensitive to antimycin A in Arabidopsis that
      overaccumulated PGR5 (PROTON GRADIENT REGULATION 5) originating from Pinus taeda
      (PtPGR5) than that in the wild type. Consistent with this in vitro observation,
      infiltration of antimycin A reduced PSII yields and the non-photochemical
      quenching (NPQ) of Chl fluorescence in wild-type leaves but not in leaves
      accumulating PtPGR5. There are eight amino acid differences between PGR5 of
      Arabidopsis (AtPGR5) and PtPGR5 in their mature forms. To determine the site
      conferring antimycin A resistance, a series of AtPGR5 and PtPGR5 variants was
      introduced into the Arabidopsis pgr5 mutant. We determined that the presence of
      lysine rather than valine at the third amino acid position was necessary and
      sufficient for resistance to antimycin A. High levels of resistance to antimycin
      A required overaccumulation of PtPGR5 in ruptured chloroplasts, suggesting that
      PtPGR5 is partly resistant to antimycin A. In contrast, PSII yield was almost
      fully resistant to antimycin A in leaves accumulating endogenous levels of PtPGR5
      or AtPGR5 V3K that had lysine instead of valine at the third position. NPQ was
      also dramatically recovered in leaves of these lines. These results imply that
      partial recovery of PSI cyclic electron transport is sufficient for maintaining
      redox homeostasis in photosynthesis. Our discovery suggests that antimycin A
      inhibits the function of PGR5 or proteins localized close to PGR5. 

PMID- 23872271
TI  - Mitochondrial phosphatidylethanolamine level modulates Cyt c oxidase activity to
      maintain respiration capacity in Arabidopsis thaliana rosette leaves.
AB  - Phosphatidylethanolamine is the predominant phospholipid of the mitochondrial
      inner membrane. In Arabidopsis, pect1-4 mutants exhibit reduced cellular
      phosphatidylethanolamine levels owing to reduced CTP:phosphorylethanolamine
      cytidylyltransferase (PECT; EC 2.7.7.14) activity. Consequently, pect1-4 mutants
      may have decreased mitochondrial phosphatidylethanolamine levels, thereby
      affecting respiration capacity. Wild-type and pect1-4 plants grew similarly under
      a short-day condition until 5 weeks, when pect1-4 leaves had slightly less Chl.
      Total respiration was comparable between wild-type and pect1-4 leaves at 3 weeks
      and then increased 2-fold in the wild-type but only 1.1-fold in pect1-4 leaves.
      Compared with the wild type, the Cyt oxidase pathway capacity was reduced by 36%
      in pect1-4 leaves at 5 weeks and by 43% in pect1-4 mitochondria in 5-week-old
      rosette leaves. Maximal Cyt c oxidase (COX) activity was 20% lower in pect1-4
      mitochondria than in wild-type mitochondria at 5 weeks despite comparable COX II
      protein levels in mitochondria at that time. Furthermore, COX II protein levels
      doubled in both wild-type and pect1-4 mitochondria between 3 and 5 weeks.
      Phosphatidylethanolamine levels were similar between mitochondria from these
      plants at 3 weeks and then increased by 6.4% in wild-type mitochondria and
      decreased by 6.5% in pect1-4 mitochondria by 5 weeks. Phosphatidylcholine levels
      compensated for the decreases in phosphatidylethanolamine levels. COX activity
      was lower in pect1-4 mitochondria at 5 weeks, most probably due to reduced
      phosphatidylethanolamine levels and/or an altered
      phosphatidylethanolamine:phosphatidylcholine ratio. Thus, PECT1 regulates
      mitochondrial phosphatidylethanolamine levels, which are important for
      maintaining respiration capacity in Arabidopsis leaves during prolonged growth
      under short-day conditions. 

PMID- 23872272
TI  - EXPANSINA17 up-regulated by LBD18/ASL20 promotes lateral root formation during
      the auxin response.
AB  - Expansins are non-hydrolytic cell wall-loosening proteins involved in a variety
      of plant developmental processes during which cell wall modification occurs. Cell
      wall remodeling proteins including expansins have been suggested to be involved
      in cell separation to facilitate the emergence of lateral roots (LRs) through the
      overlaying tissues of the primary root. LBD18/ASL20 activates EXPANSINA14
      (EXPA14) expression by directly binding to the EXPA14 promoter to enhance LR
      emergence in Arabidopsis thaliana. Here we show that EXPA17 is another target
      gene regulated by LBD18 to promote LR formation in Arabidopsis. We showed that
      nuclear translocation of the LBD18:GR fusion protein expressed under the
      Cauliflower mosaic virus (CaMV) 35S promoter or under the LBD18 promoter by
      dexamethasone treatment results in an increase in EXPA17 transcript levels. beta
      Glucuronidase (GUS) expression under the EXPA17 promoter, which is detected only
      in the roots of the wild type, was reduced in the LR primordium and overlaying
      tissues in an lbd18 mutant background. The number of emerged LRs of the EXPA17
      RNAi (RNA interference) Arabidopsis lines was significantly lower than that of
      the wild type. Overexpression of EXPA17 in Arabidopsis increased the density of
      emerged LRs in the presence of auxin compared with the wild type. LR induction
      experiments with a gravitropic stimulus showed that LR emergence is delayed in
      the EXPA17 RNAi plants compared with the wild type. In addition, EXPA4 expression
      was also detected in overlaying tissues of the LR primordium and was inducible by
      LBD18. Taken together, these results support the notion that LBD18 up-regulates a
      subset of EXP genes to enhance cell separation to promote LR emergence in
      Arabidopsis. 

PMID- 23872274
TI  - Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer
      cells.
AB  - Pancreatic cancer is notorious for its difficult diagnosis at early stage and
      poor recurrence-free prognosis. This study aimed to investigate the possible
      involvement of Oct4 and Nanog in pancreatic cancer. The high expressions of Oct4
      and Nanog in human pancreatic cancer tissues were found to indicate a worse
      prognostic value of patients. The pancreatic cancer stem cells (PCSCs) that
      isolated from PANC-1 cell line by flow cytometry exhibited high expressions of
      Oct4 and Nanog. To investigate whether Oct4 and Nanog play crucial role in
      maintaining the stemness of PCSCs, double knockdown of Oct4 and Nanog
      demonstrated that Oct4 and Nanog significantly reduced proliferation, migration,
      invasion, chemoresistance, and tumorigenesis of PCSCs in vitro and in vivo. The
      altered expression of the genes related to pancreatic carcinogenesis, metastasis,
      drug resistance and epithelial-mesenchymal transdifferentiation (EMT) might
      affect the biological characteristics of PCSCs. Our results suggest that Oct4 and
      Nanog may serve as a potential marker of prognosis and a novel target of therapy
      for pancreatic cancer. 

PMID- 23872273
TI  - Triacylglycerol mobilization is suppressed by brefeldin A in Chlamydomonas
      reinhardtii.
AB  - Brefeldin A suppresses vesicle trafficking by inhibiting exchange of GDP for GTP
      in ADP-ribosylation factor. We report that brefeldin A suppresses mobilization of
      triacylglycerols in Chlamydomonas reinhardtii, a model organism of green
      microalgae. Analyses revealed that brefeldin A causes Chlamydomonas to form lipid
      droplets in which triacylglycerols accumulate in a dose-dependent manner. Pulse
      labeling experiment using fluorescent fatty acids suggested that brefeldin A
      inhibits the cells from degrading fatty acids. The experiment also revealed that
      the cells transiently form novel compartments that accumulate exogenously added
      fatty acids in the cytoplasm, designated fatty acid-induced microbodies (FAIMs).
      Brefeldin A up-regulates the formation of FAIMs, whereas nitrogen deprivation
      that up-regulates triacylglycerol synthesis in Chlamydomonas does not cause the
      cells to form FAIMs. These results underscore the role of the vesicle trafficking
      machinery in triacylglycerol metabolism in green microalgae. 

PMID- 23872275
TI  - Therapeutic enhancement of vascular-targeted photodynamic therapy by inhibiting
      proteasomal function.
AB  - Vascular-targeted photodynamic therapy (vPDT) is a novel vascular targeting
      modality based on site-directed delivery of a photosensitizer to tumor
      vasculature, which induces reactive oxygen species (ROS)-mediated vascular
      effects upon light activation. To enhance the therapeutic outcome of vPDT, we
      combined proteasomal inhibitor bortezomib and vPDT using photosensitizer
      verteporfin in the present study. We found that bortezomib in combination with
      verteporfin-PDT induced more accumulation of ubiquitinated proteins and apoptosis
      in endothelial cells than each individual treatment. The combination therapy also
      enhanced vPDT-induced inhibition in tumor growth. These results indicate that
      bortezomib can be used together with verteporfin-PDT for enhanced treatment
      outcome. 

PMID- 23872276
TI  - Thiophosphate and thiophosphonate analogues of glucose-1-phosphate: synthesis and
      enzymatic activity with a thymidylyltransferase.
AB  - Synthetic methods were investigated for the preparation of O and S-glucosyl
      thiophosphates and glucosyl 1C-thiophosphonate. Four protected glucosyl
      thiophosphate compounds were synthesized and characterized as precursors to
      glucose 1-thiophosphate. The effect of various reaction conditions and the nature
      of the carbohydrate and thiophosphate protecting groups and how they impact both
      the yields and alpha/beta diastereoselectivity of the glucosyl thiophosphate
      products were explored. A novel isomerization from an O-linked to S-linked
      glucosyl thiophosphate was observed. alpha-D-Glucose-1C-thiophosphonate was
      synthesized and evaluated as a substrate for the thymidylyltransferase, Cps2L.
      Tandem mass spectrometric analysis determined the position of sulfur in the sugar
      nucleotide product.

PMID- 23872277
TI  - Computational proteomics: designing a comprehensive analytical strategy.
AB  - The proper combination of proteomics with bioinformatics is highly synergistic,
      capable of propelling proteomics into a truly high-throughput platform. However,
      appropriate experimental design and analytical considerations are needed to
      maximize analytical outcome. This review highlights key issues and caveats in
      converting raw data to protein identifications, and subsequently biological
      insight. It offers some insights on how the establishment of highly robust
      proteomics pipelines can be used for studying novel areas such as computational
      epigenetics, high performance functional studies and new discovery paradigms for
      drug targets and biomarkers. 

PMID- 23872278
TI  - Generation and utility of genetically humanized mouse models.
AB  - Identifying in vivo models that are naturally predictive for particular areas of
      study in humans can be challenging due to the divergence that has occurred during
      speciation. One solution to this challenge that is gaining increasing traction is
      the use of genetic engineering to introduce human genes into mice to generate
      superior models for predicting human responses. This review describes the state
      of-the-art for generating such models, provides an overview of the types of
      genetically humanized mouse models described to date and their applications in
      basic research, drug discovery and development and to understand clinical drug
      toxicity. We discuss limitations and explore promising future directions for the
      use of genetically humanized mice to further improve translational research. 

PMID- 23872279
TI  - Repeated agouti related peptide (83-132) injections inhibit cocaine-induced
      locomotor sensitisation, but not via the nucleus accumbens.
AB  - Drug addiction is a chronic relapsing brain disease for which many of the
      underlying neuronal mechanisms are yet to be unravelled. There seems to be an
      interaction between the melanocortin system and drugs of abuse. For instance,
      infusion of the melanocortin MC4 receptor antagonist SHU9119 (Ac-Nle-cyclo(-Asp
      His-D-2-Nal-Arg-Trp-Lys)-NH2) into the nucleus accumbens results in conditioned
      place avoidance, reduces the amount of lever presses for cocaine and blocks
      development of cocaine-induced locomotor sensitisation. The aim of this study is
      to determine whether the induction of locomotor sensitisation to repeated cocaine
      is inhibited by the melanocortin MC4 receptor inverse agonist Agouti Related
      Peptide (AgRP83-132). Rats were sensitised to daily cocaine injections for 5
      consecutive days and 30 min prior to every daily cocaine injection, rats received
      an intracerebroventricular (i.c.v.) or intra nucleus accumbens injection with
      AgRP(83-132) or saline, to determine whether we could inhibit cocaine-induced
      locomotor sensitisation. We show that i.c.v. injections of AgRP(83-132) inhibit
      cocaine-induced locomotor sensitisation. This effect is not regulated via the
      nucleus accumbens, since injecting the melanocortin receptor inverse agonist
      AgRP(83-132) directly into the nucleus accumbens was unable to inhibit the
      cocaine-induced locomotor sensitisation. This implicates that the nucleus
      accumbens is an unlikely site to inhibit the induction of locomotor sensitisation
      via the melanocortin MC4 receptor. This is in contrast to other studies that show
      an effect of the melanocortin MC4 receptor antagonist SHU9119 on locomotor
      sensitisation when injected into the nucleus accumbens.

PMID- 23872280
TI  - D-xylose-fermenting and xylanase-producing yeast species from rotting wood of two
      Atlantic Rainforest habitats in Brazil.
AB  - This study investigated the yeast species associated with rotting wood in
      Brazilian Atlantic Rainforest ecosystems focusing on the identification of D
      xylose-fermenting and/or xylanase-producing species. A total of 321 yeast strains
      were isolated from rotting wood samples collected in two Atlantic Rainforest
      areas. These samples were cultured in yeast nitrogen base (YNB)-D-xylose or YNB
      xylan media. Schwanniomyces polymorphus, Scheffersomyces queiroziae, Barnettozyma
      californica, and Candida (Ogataea) boidinii were the most frequently isolated
      yeasts. The rarefaction curves for the yeast communities isolated in YNB-D-xylose
      and YNB-xylan from both areas continued to rise and did not reach an asymptote,
      indicating that not all yeast diversity had been recovered. Additionally, the
      yeast composition was variable among the samples and areas, which was confirmed
      by the values of the Sorensen index. Among the 69 species identified, only 12
      were found in both areas sampled. Fifteen possible new species were obtained.
      Among them, two species (Sugiyamaella sp. 1 and Sugiyamaella xylanicola) showed
      the ability to ferment D-xylose into ethanol, and three species
      (Spencermartinsiella sp. 1, Su. xylanicola and Tremella sp.) were able to produce
      extracellular xylanases. Indeed, most of the xylanase-producing isolates belong
      to the new species Su. xylanicola, which was also positive for D-xylose
      fermentation. S.queiroziae and S. stipitis were the main D-xylose-fermenting
      yeasts identified. The results of this work showed that rotting wood collected
      from the Atlantic Rainforests is a huge source of yeasts, including new species,
      with promising biotechnological properties. 

PMID- 23872281
TI  - Microbial culture collections as pillars for promoting fungal diversity,
      conservation and exploitation.
AB  - Fungi are a diverse group of organisms with an overall global number of 1.5M up
      to 3.3M species on Earth. Besides their ecological roles as decomposers, fungi
      are important in several aspects of applied research. Here, we review how culture
      collections may promote the knowledge on diversity, conservation and
      biotechnological exploitation of fungi. The impact of fungi diversity on
      biotechnological studies is discussed. We point out the major roles of microbial
      repositories, including fungal preservation, prospecting, identification,
      authentication and supply. A survey on the World Data Center for Microorganisms
      (WDCM) powered by the World Federation for Culture Collections and on the Genetic
      Heritage Management Council (CGEN) database revealed that 46 Brazilian culture
      collections registered in these databases are dedicate to preserving fungi. Most
      of these culture collections are located in the Southeast of Brazil. This
      scenario also demonstrates that Brazil has many collections focused on fungal
      strains, but the lack of up-to-date information in WDCM as well as of a solid
      national platform for culture collections registration do not allow accurate
      assessment of fungal preservation. 

PMID- 23872282
TI  - WikiLeaks of lead extraction: do we know the truth about Fidelis and Riata?

PMID- 23872284
TI  - Reaction time variability in ADHD: a meta-analytic review of 319 studies.
AB  - Individuals with ADHD are characterized as ubiquitously slower and more variable
      than their unaffected peers, and increased reaction time (RT) variability is
      considered by many to reflect an etiologically important characteristic of ADHD.
      The present review critically evaluates these claims through meta-analysis of 319
      studies of RT variability in children, adolescents, and adults with ADHD relative
      to typically developing (TD) groups, clinical control groups, and themselves
      (subtype comparisons, treatment and motivation effects). Random effects models
      corrected for measurement unreliability and publication bias revealed that
      children/adolescents (Hedges' g=0.76) and adults (g=0.46) with ADHD demonstrated
      greater RT variability relative to TD groups. This increased variability was
      attenuated by psychostimulant treatment (g=-0.74), but unaffected by non
      stimulant medical and psychosocial interventions. Individuals with ADHD did not
      evince slower processing speed (mean RT) after accounting for RT variability,
      whereas large magnitude RT variability deficits remained after accounting for
      mean RT. Adolescents and adults with ADHD were indistinguishable from clinical
      control groups, and children with ADHD were only minimally more variable than
      clinical control children (g=0.25). Collectively, results of the meta-analysis
      indicate that RT variability reflects a stable feature of ADHD and other clinical
      disorders that is robust to systematic differences across studies. 

PMID- 23872283
TI  - Evaluation of dried blood spot diagnosis using HIV1-DNA and HIV1-RNA Biocentric
      assays in infants in Abidjan, Cote d'Ivoire. The Pedi-Test DBS ANRS 12183 Study.
AB  - This study evaluates HIV infant diagnosis on DBS using Biocentric HIV1-DNA and
      HIV1-RNA assays, in field conditions in Cote d'Ivoire. Paediatric screening was
      offered to children<=3 years in clinical sites in Cote d'Ivoire in 2008. For each
      HIV-infected child, two non-infected children were included and blood samples
      were collected. HIV-DNA results obtained on EDTA blood samples with Biocentric
      assay were the reference for HIV infant diagnosis. Plasma and DBS viral loads
      were measured using HIV-RNA Biocentric assay. DBS samples were also tested for
      HIV-DNA detection using both Biocentric and Amplicor Roche assays. Sensitivity,
      specificity and concordance between tests were calculated. Overall samples from
      138 HIV-exposed children, 46 infected, 92 non-infected were included. All tests
      were 100% sensitive and specific including 100% concordance with the two HIV-DNA
      assays. The median level of HIV-DNA on EDTA samples was 3.15 log10 copies/10(6)
      PBMCs; the median level of HIV RNA in plasma and DBS were respectively 5.82 and
      5.17 log10 copies/ml (Pearson's correlation R2=0.92, p<0.0001). The threshold for
      detectable HIV-RNA on DBS was 3.3 log10. Although there are differences between
      viral load measured on DBS and plasma, the two Biocentric assays present very
      good performances for HIV infant diagnosis on DBS while cheap and feasible.

PMID- 23872285
TI  - Neural correlates of audiovisual speech processing in a second language.
AB  - Neuroimaging studies of audiovisual speech processing have exclusively addressed
      listeners' native language (L1). Yet, several behavioural studies now show that
      AV processing plays an important role in non-native (L2) speech perception. The
      current fMRI study measured brain activity during auditory, visual, audiovisual
      congruent and audiovisual incongruent utterances in L1 and L2. BOLD responses to
      congruent AV speech in the pSTS were stronger than in either unimodal condition
      in both L1 and L2. Yet no differences in AV processing were expressed according
      to the language background in this area. Instead, the regions in the bilateral
      occipital lobe had a stronger congruency effect on the BOLD response (congruent
      higher than incongruent) in L2 as compared to L1. According to these results,
      language background differences are predominantly expressed in these unimodal
      regions, whereas the pSTS is similarly involved in AV integration regardless of
      language dominance. 

PMID- 23872287
TI  - Proximity to terror and post-traumatic stress: a follow-up survey of governmental
      employees after the 2011 Oslo bombing attack.
AB  - OBJECTIVE: To assess the prevalence of post-traumatic stress disorder (PTSD)
      symptoms among governmental employees after the 2011 Oslo bombing attack targeted
      towards the Norwegian Ministries, and to explore the importance of proximity to
      the bomb explosion as a predictor of PTSD. DESIGN: A cross-sectional study.
      SETTING: Data were collected from a survey 10 months after the Oslo bombing on 22
      July 2011. PARTICIPANTS: A total of 3520 employees were invited to the study. Net
      samples comprised 1927 employees in 14 of the 17 Norwegian Ministries. OUTCOME
      MEASURES: The employees reported where they were at the time of the explosion.
      PTSD was assessed with the Norwegian version of the PTSD checklist (PCL).
      RESULTS: A total of 207 of the 1881 (11%) ministerial employees who completed the
      survey were present at work when the bomb exploded. Of these, a quarter (24%, 95%
      CI 18.4 to 30.0) had symptom levels equivalent to PTSD, while the prevalence was
      approximately 4% among those not present at work. In the latter group the
      prevalence was similar irrespective of whether their location was in Oslo, other
      places in Norway or abroad. Leadership responsibility was associated with lower
      risk for PTSD. CONCLUSIONS: The risk of PTSD is mainly associated with being
      present at work at the time of a terror attack. For those not present at work,
      the risk of PTSD is low and independent of proximity to the terror scene. The
      findings may have implications for planning and priority of healthcare services
      after a work place terror attack.

PMID- 23872286
TI  - Computational modeling of stuttering caused by impairments in a basal ganglia
      thalamo-cortical circuit involved in syllable selection and initiation.
AB  - Atypical white-matter integrity and elevated dopamine levels have been reported
      for individuals who stutter. We investigated how such abnormalities may lead to
      speech dysfluencies due to their effects on a syllable-sequencing circuit that
      consists of basal ganglia (BG), thalamus, and left ventral premotor cortex
      (vPMC). "Neurally impaired" versions of the neurocomputational speech production
      model GODIVA were utilized to test two hypotheses: (1) that white-matter
      abnormalities disturb the circuit via corticostriatal projections carrying copies
      of executed motor commands and (2) that dopaminergic abnormalities disturb the
      circuit via the striatum. Simulation results support both hypotheses: in both
      scenarios, the neural abnormalities delay readout of the next syllable's motor
      program, leading to dysfluency. The results also account for brain imaging
      findings during dysfluent speech. It is concluded that each of the two
      abnormality types can cause stuttering moments, probably by affecting the same BG
      thalamus-vPMC circuit. 

PMID- 23872288
TI  - Association of work-related stress with mental health problems in a special
      police force unit.
AB  - OBJECTIVES: Law and order enforcement tasks may expose special force police
      officers to significant psychosocial risk factors. The aim of this work is to
      investigate the relationship between job stress and the presence of mental health
      symptoms while controlling sociodemographical, occupational and personality
      variables in special force police officers. METHOD: At different time points, 292
      of 294 members of the 'VI Reparto Mobile', a special police force engaged
      exclusively in the enforcement of law and order, responded to our invitation to
      complete questionnaires for the assessment of personality traits, work-related
      stress (using the Demand-Control-Support (DCS) and the Effort-Reward-Imbalance
      (ERI) models) and mental health problems such as depression, anxiety and burnout.
      RESULTS: Regression analyses showed that lower levels of support and reward and
      higher levels of effort and overcommitment were associated with higher levels of
      mental health symptoms. Psychological screening revealed 21 (7.3%) likely cases
      of mild depression (Beck Depression Inventory, BDI>=10). Officers who had
      experienced a discrepancy between work effort and rewards showed a marked
      increase in the risk of depression (OR 7.89, 95% CI 2.32 to 26.82) when compared
      with their counterparts who did not perceive themselves to be in a condition of
      distress. CONCLUSIONS: The findings of this study suggest that work-related
      stress may play a role in the development of mental health problems in police
      officers. The prevalence of mental health symptoms in the cohort investigated
      here was low, but not negligible in the case of depression. Since special forces
      police officers have to perform sensitive tasks for which a healthy psychological
      functioning is needed, the results of this study suggest that steps should be
      taken to prevent distress and improve the mental well-being of these workers.

PMID- 23872289
TI  - Belimumab: a technological advance for systemic lupus erythematosus patients?
      Report of a systematic review and meta-analysis.
AB  - OBJECTIVES: To undertake a systematic review and meta-analysis to investigate
      clinical effectiveness of belimumab for patients with systemic lupus
      erythematosus (SLE) and antinuclear and/or anti-double-stranded DNA (dsDNA)
      autoantibodies. METHODS: We searched eight electronic databases and reference
      lists for randomised controlled trials (RCTs) of belimumab against placebo or
      best supportive care. Quality assessment and random effects meta-analysis were
      undertaken. DESIGN: A meta-analysis of RCTs. PARTICIPANTS: 2133 SLE patients.
      PRIMARY AND SECONDARY OUTCOME MEASURES: SLE Responder Index (SRI) at week 52.
      RESULTS: Three double-blind placebo-controlled RCTs (L02, BLISS-52 BLISS-76)
      investigated 2133 SLE patients. BLISS-52 and BLISS-76 trials recruited patients
      with antinuclear and/or anti-dsDNA autoantibodies and demonstrated belimumab
      effectiveness for the SRI at week 52. Ethnicity and geographical location of
      participants varied considerably between BLISS trials. Although tests for
      statistical heterogeneity were negative, BLISS-52 results were systematically
      more favourable for all measured outcomes. Meta-analysis of pooled 52-week SRI
      BLISS results showed benefit for belimumab (OR 1.63, 95% CI 1.27 to 2.09). By
      week 76, the primary SRI outcome in BLISS-76 was not statistically significant
      (OR 1.31, 95% CI 0.919 to 1.855).

PMID- 23872290
TI  - Phase II single arm open label multicentre clinical trial to evaluate the
      efficacy and side effects of a combination of gefitinib and methotrexate to treat
      tubal ectopic pregnancies (GEM II): study protocol.
AB  - INTRODUCTION: Tubal ectopic pregnancy (tEP) is the most common life-threatening
      condition in gynaecology. tEPs with pretreatment serum human chorionic
      gonadotrophin (hCG) levels <1000 IU/L respond well to outpatient medical
      treatment with intramuscular methotrexate (MTX). TEPs with hCG >1000 IU/L take a
      significant time to resolve with MTX and require multiple outpatient monitoring
      visits. Gefitinib is an orally active epidermal growth factor receptor (EGFR)
      antagonist. In preclinical studies, we found that EP implantation sites express
      high levels of EGFR and that gefitinib augments MTX-induced regression of
      pregnancy-like tissue. We performed a phase I toxicity study administering oral
      gefitinib and intramuscular MTX to 12 women with tEPs. The combination therapy
      did not cause significant toxicities and was well tolerated. We noted that
      combination therapy resolved the tEPs faster than MTX alone. We now describe the
      protocol of a larger single arm trial to estimate the efficacy and side effects
      of combination gefitinib and MTX to treat stable tEPs with hCG 1000-10 000 IU/L
      METHODS AND ANALYSIS: We propose to undertake a single-arm multicentre open label
      trial (in Edinburgh and Melbourne) and recruit 28 women with tEPs (pretreatment
      serum hCG 1000-10 000 IU/L). We intend to give a single dose of intramuscular MTX
      (50 mg/m(2)) and oral gefitinib (250 mg) daily for 7 days. Our primary outcome is
      the resolution of EP to non-pregnant hCG levels <15 IU/L without requirement of
      surgery. Our secondary outcomes are comparison of time to resolution against
      historical controls given MTX only, and safety and tolerability as determined by
      clinical/biochemical assessment. ETHICS AND DISSEMINATION: Ethical approval has
      been obtained from Scotland A Research Ethics Committee (MREC 11/AL/0350),
      Southern Health Human Research Ethics Committee B (HREC 11180B) and the Mercy
      Health Human Research Ethics Committee (R12/25). Data will be presented at
      international conferences and published in peer-reviewed journals. TRIAL
      REGISTRATION NUMBER: ACTRN12611001056987.

PMID- 23872291
TI  - Soft drink intake and progression of radiographic knee osteoarthritis: data from
      the osteoarthritis initiative.
AB  - OBJECTIVES: We examine the prospective association of soft drink consumption with
      radiographic progression of knee osteoarthritis (OA). DESIGN: Prospective cohort
      study. SETTING: This study used data from the osteoarthritis initiative (OAI).
      PARTICIPANTS: In OAI, 2149 participants with radiographic knee OA and having
      dietary data at baseline were followed up to 12, 24, 36 and 48 months. MEASURES:
      The soft drink consumption was assessed with a Block Brief Food Frequency
      Questionnaire completed at baseline. To evaluate knee OA progression, we used
      quantitative medial tibiofemoral joint space width (JSW) based on plain
      radiographs. The multivariate linear models for repeated measures were used to
      test the independent association between soft drink intake and the change in JSW
      over time, while adjusting for body mass index and other potential confounding
      factors. RESULTS: In stratified analyses by gender, we observed a significant
      dose-response relationship between baseline soft drink intake and adjusted mean
      change of JSW in men. With increasing levels of soft drink intake (none, <=1, 2-4
      and >=5 times/week), the mean decreases of JSW were 0.31, 0.39, 0.34 and 0.60 mm,
      respectively. When we further stratified by obesity, a stronger dose-response
      relationship was found in non-obese men. In obese men, only the highest soft
      drink level (>=5 times/week) was associated with increased change in JSW compared
      with no use. In women, no significant association was observed. CONCLUSIONS: Our
      results suggest that frequent consumption of soft drinks may be associated with
      increased OA progression in men. Replication of these novel findings in other
      studies demonstrating the reduction in soft drink consumption leads to delay in
      OA progression is needed.

PMID- 23872292
TI  - A pilot study on record reviewing with a priori patient selection.
AB  - OBJECTIVES: To investigate whether a priori selection of patient records using
      unexpectedly long length of stay (UL-LOS) leads to detection of more records with
      adverse events (AEs) compared to non-UL-LOS. DESIGN: To investigate the
      opportunities of the UL-LOS, we looked for AEs in all records of patients with
      colorectal cancer. Within this group, we compared the number of AEs found in
      records of patients with a UL-LOS with the number found in records of patients
      who did not have a UL-LOS. SETTING: Our study was done at a general hospital in
      The Netherlands. The hospital is medium sized with approximately 30 000
      admissions on an annual basis. The hospital has two major locations in different
      cities where both primary and secondary care is provided. PARTICIPANTS: The
      patient records of 191 patients with colorectal cancer were reviewed. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Number of triggers and adverse events were the
      primary outcome measures. RESULTS: In the records of patients with colorectal
      cancer who had a UL-LOS, 51% of the records contained one or more AEs compared
      with 9% in the reference group of non-UL-LOS patients. By reviewing only the UL
      LOS group with at least one trigger, we found in 84% (43 out of 51) of these
      records at least one adverse event. CONCLUSIONS: A priori selection of patient
      records using the UL-LOS indicator appears to be a powerful selection method
      which could be an effective way for healthcare professionals to identify
      opportunities to improve patient safety in their day-to-day work.

PMID- 23872293
TI  - Non-communicable diseases, infection and survival in a retrospective cohort of
      Indigenous and non-Indigenous adults in central Australia.
AB  - OBJECTIVES: We hypothesise that rising prevalence rates of non-communicable
      diseases (NCDs) increase infection risk and worsen outcomes among socially
      disadvantaged Indigenous Australians undergoing a rapid epidemiological
      transition. DESIGN: Available pathology, imaging and discharge morbidity codes
      were retrospectively reviewed for a period of 5 years prior to admission with a
      bloodstream infection (BSI), 1 January 2003 to 30 June 2007. PARTICIPANTS: 558
      Indigenous and 55 non-Indigenous community residents of central Australia.
      OUTCOME MEASURES: The effects of NCDs on risk of infection and death were
      determined after stratifying by ethnicity. RESULTS: The mean annual BSI incidence
      rates were far higher among Indigenous residents (Indigenous, 937/100 000; non
      Indigenous, 64/100 000 person-years; IRR=14.6; 95% CI 14.61 to 14.65, p<0.001).
      Indigenous patients were also more likely to have previous bacterial infections
      (68.7% vs 34.6%; respectively, p<0.001), diabetes (44.3% vs 20%; p<0.001),
      harmful alcohol consumption (37% vs 12.7%; p<0.001) and other communicable
      diseases (human T-lymphotropic virus type 1, 45.2%; strongyloidiasis, 36.1%;
      hepatitis B virus, 12.9%). Among Indigenous patients, diabetes increased the odds
      of current Staphylococcus aureus BSI (OR=1.6, 95% CI 1.0 to 2.5) and prior skin
      infections (adjusted OR=2.1, 95% CI 1.4 to 3.3). Harmful alcohol consumption
      increased the odds of current Streptococcus pneumoniae BSI (OR=1.57, 95% CI 1.02
      to 2.40) and of previous BSI (OR=1.7, 95% CI 1.1 to 2.5), skin infection (OR=1.7,
      95% CI 1.1 to 2.6) or pneumonia (OR=4.3, 95% CI 2.8 to 6.7). Twenty-six per cent
      of Indigenous patients died at a mean (SD) age of 47+/-15 years. Complications of
      diabetes and harmful alcohol consumption predicted 28-day mortality (non
      rheumatic heart disease, HR=2.9; 95% CI 1.4 to 6.2; chronic renal failure,
      HR=2.6, 95%CI 1.0 to 6.5; chronic liver disease, HR=3.3, 95% CI 1.6 to 6.7).
      CONCLUSIONS: In a socially disadvantaged population undergoing a rapid
      epidemiological transition, NCDs are associated with an increased risk of
      infection and BSI-related mortality. Complex interactions between communicable
      diseases and NCDs demand an integrated approach to management, which must include
      the empowerment of affected populations to promote behavioural change.

PMID- 23872294
TI  - Chronic disease multimorbidity transitions across healthcare interfaces and
      associated costs: a clinical-linkage database study.
AB  - OBJECTIVE: To investigate multimorbidity transitions from general practice
      populations across healthcare interfaces and the associated healthcare costs.
      DESIGN: Clinical-linkage database study. SETTING: Population (N=60 660) aged 40
      years and over registered with 53 general practices in Stoke-on-Trent.
      PARTICIPANTS: Population with six specified multimorbidity pairs were identified
      based on hypertension, diabetes mellitus (DM), coronary heart disease (CHD),
      chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) and
      chronic kidney disease (CKD). MAIN OUTCOMES MEASURES: Chronic disease registers
      were linked to accident and emergency (A&E) and hospital admissions for a 3-year
      time period (2007-2009), and associated costs measured by Healthcare Resource
      Groups. Associations between multimorbid groups and direct healthcare costs were
      compared with their respective single disease groups using linear regression
      methods, adjusting for age, gender and deprivation. RESULTS: In the study
      population, there were 9735 patients with hypertension and diabetes (16%), 3574
      with diabetes and CHD (6%), 2894 with diabetes and CKD (5%), 1855 with COPD and
      CHD (3%), 754 with CHF and COPD (1%) and 1425 with CHF and CKD (2%). Transition,
      defined as at least one episode in each of the 3-year time periods, was as
      follows: patients with hypertension and DM had the fewest transitions in the 3
      year time period (37% A&E episode and 51% hospital admission), but those with CHF
      and CKD had the most transitions (67% A&E episode and 79% hospital admission).
      The average 3-year total costs per multimorbid patient for A&E episodes ranged
      from L69 to L166 and for hospital admissions ranged from between L2289 and L5344.
      The adjusted costs were significantly higher for all six multimorbid groups
      compared with their respective single disease groups. CONCLUSIONS: Specific
      common multimorbid pairs are associated with higher healthcare transitions and
      differential costs. Identification of multimorbidity type and linkage of
      information across interfaces provides opportunities for targeted intervention
      and delivery of integrated care.

PMID- 23872295
TI  - A study protocol for performance evaluation of a new academic intensive care unit
      facility: impact on patient care.
AB  - BACKGROUND: Healthcare facility construction is increasing because of population
      demand and the need to replace ageing infrastructure. Research suggests that
      there may be a relationship between healthcare environment and patient care. To
      date, most evaluations of new healthcare facilities are derived from techniques
      used in other industries and focus on physical, financial and architectural
      performance. However, few studies have evaluated the impact of healthcare
      facility design on processes and outcomes of patient care. STUDY AIMS: The
      primary objective of this study was to investigate the impact of relocation to a
      new intensive care unit (ICU) facility on clinical performance measures. This
      study also proposes to develop and test a framework for facility performance
      evaluation using accepted ICU design guidelines and Donabedian's model for
      healthcare quality. METHODS AND ANALYSIS: We will utilise a mixed-methods,
      observational, retrospective, controlled, before-and-after design to take
      advantage of the quasiexperimental conditions created with the construction of a
      new ICU facility in Calgary, Canada. For the qualitative substudy, we will
      conduct individual interviews with end-users to understand their impressions and
      experiences with the new environment and perform thematic analysis. For the
      quantitative substudy, we will compare process of care indicators and patient
      outcomes for the 12-month period before and after relocation to the new facility.
      Two other local ICU facilities that did not undergo structural change during the
      study period will serve as controls. We will triangulate qualitative and
      quantitative results utilising a novel framework. ETHICS AND DISSEMINATION: The
      results of this study will contribute in understanding the impact of new ICU
      facilities on clinical performance measures centred on patients, their families
      and healthcare providers. The framework will complement existing building
      performance evaluation techniques and help healthcare administrators plan new ICU
      facilities. The University of Calgary Research Ethics Board approved this study
      protocol.

PMID- 23872296
TI  - Adherence management for patients with cancer taking capecitabine: a prospective
      two-arm cohort study.
AB  - OBJECTIVE: To develop and evaluate a multiprofessional modular medication
      management to assure adherence to capecitabine. METHODS: The study was conducted
      as a prospective, multicentred observational cohort study. All participants
      received pharmaceutical care consisting of oral and written information. Daily
      adherence was defined as percentage of days with correctly administered
      capecitabine doses and assessed using medication event monitoring. According to
      their daily adherence during the first cycle, patients were identified as
      initially non-adherent (<90% adherence) or adherent (>=90% adherence). Initially
      non-adherent patients received additional adherence support. RESULTS: Seventy
      three patients with various tumour entities were enrolled, 58 were initially
      adherent and 15 non-adherent. Median daily adherence of initially non-adherent
      patients increased from 85.7% to 97.6% during the observation period of six
      cycles. Throughout all cycles, median daily adherence of initially adherent
      patients was 100.0%. Daily adherence was not associated with sociodemographic and
      disease-related factors. No patient was non-persistent. CONCLUSIONS: An early
      adherence screening effectively distinguishes between patients adhering and non
      adhering to capecitabine. The provision of specific adherence support is
      associated with enhanced adherence of initially non-adherent patients, whereas
      initially adherent patients remain adherent for at least six cycles without
      specific support. Our needs-based approach helps to use available resources for
      adherence management efficiently.

PMID- 23872297
TI  - Explaining the barriers to and tensions in delivering effective healthcare in UK
      care homes: a qualitative study.
AB  - OBJECTIVE: To explain the current delivery of healthcare to residents living in
      UK care homes. DESIGN: Qualitative interview study using a grounded theory
      approach. SETTING: 6 UK care homes and primary care professionals serving the
      homes. PARTICIPANTS: Of the 32 participants, there were 7 care home managers, 2
      care home nurses, 9 care home assistants, 6 general practitioners (GPs), 3
      dementia outreach nurses, 2 district nurses, 2 advanced nurse practitioners and 1
      occupational therapist. RESULTS: 5 themes were identified: complex health needs
      and the intrinsic nature of residents' illness trajectories; a mismatch between
      healthcare requirements and GP time; reactive or anticipatory healthcare?; a
      dissonance in healthcare knowledge and ethos; and tensions in the responsibility
      for the healthcare of residents. Care home managers and staff were pivotal to
      healthcare delivery for residents despite their perceived role in social care
      provision. Formal healthcare for residents was primarily provided via one or more
      GPs, often organised to provide a reactive service that did not meet residents'
      complex needs. Deficiencies were identified in training required to meet
      residents' needs for both care home staff as well as GPs. Misunderstandings,
      ambiguities and boundaries around roles and responsibilities of health and social
      care staff limited the development of constructive relationships. CONCLUSIONS:
      Healthcare of care home residents is difficult because their needs are complex
      and unpredictable. Neither GPs nor care home staff have enough time to meet these
      needs and many lack the prerequisite skills and training. Anticipatory care is
      generally held to be preferable to reactive care. Attempts to structure care to
      make it more anticipatory are dependent on effective relationships between GPs
      and care home staff and their ability to establish common goals. Roles and
      responsibilities for many aspects of healthcare are not made explicit and this
      risks poor outcomes for residents.

PMID- 23872298
TI  - An IgE multiple myeloma: contradictory findings in clinical laboratory testing.
AB  - BACKGROUND: IgE multiple myeloma is a rare kind of plasma cell disorder,
      characterized by an aggressive clinical course, where laboratory testing plays a
      fundamental role for the correct diagnosis in order to start a targeted therapy.
      In the present paper it is described a case of IgE myeloma where contradictory
      findings between immunometric and separative techniques were found. MATERIALS AND
      METHODS: Serum and 24h urine samples were tested using electrophoresis and
      immunofixation electrophoresis employing IgE antiserum and IgE were quantified
      using an immunometric method. RESULTS: Serum immunofixation evidenced a
      monoclonal band ascribable to IgE lambda and IgE serum concentration was 1,364,00
      kU/L. Urine electrophoresis evidenced a band compatible with IgE, and urine
      concentration was 2715 kU/L. On the contrary in the immunofixation of the urine
      sample no band reacting with IgE antiserum was found. CONCLUSIONS: Considering
      that the immunometric method measured IgE in urine sample and the electrophoresis
      of urine sample evidenced a band compatible with IgE, the explanation could be
      that during renal filtration or because of some characteristics related to urine
      matrix, the immunoglobulin IgE could had been modified in the site recognized by
      the antiserum used in immunofixation, and not in the one used in the immunometric
      method.

PMID- 23872299
TI  - Spatial and temporal RF electromagnetic field exposure of children and adults in
      indoor micro environments in Belgium and Greece.
AB  - Personal radio frequency electromagnetic field (RF-EMF) exposure, or exposimetry,
      is gaining importance in the bioelectromagnetics community but only limited data
      on personal exposure is available in indoor areas, namely schools, creches,
      homes, and offices. Most studies are focused on adult exposure, whereas indoor
      microenvironments, where children are exposed, are usually not considered. A
      method to assess spatial and temporal indoor exposure of children and adults is
      proposed without involving the subjects themselves. Moreover, maximal possible
      daily exposure is estimated by combining instantaneous spatial and temporal
      exposure. In Belgium and Greece, the exposure is measured at 153 positions spread
      over 55 indoor microenvironments with spectral equipment. In addition, personal
      exposimeters (measuring EMFs of people during their daily activities) captured
      the temporal exposure variations during several days up to one week at 98
      positions. The data were analyzed using the robust regression on order statistics
      (ROS) method to account for data below the detection limit. All instantaneous and
      maximal exposures satisfied international exposure limits and were of the same
      order of magnitude in Greece and Belgium. Mobile telecommunications and radio
      broadcasting (FM) were most present. In Belgium, digital cordless phone (DECT)
      exposure was present for at least 75% in the indoor microenvironments except for
      schools. Temporal variations of the exposure were mainly due to variations of
      mobile telecommunication signals. The exposure was higher during daytime than at
      night due to the increased voice and data traffic on the networks. Total exposure
      varied the most in Belgian creches (39.3%) and Greek homes (58.2%). 

PMID- 23872300
TI  - IL-6 is a predictive biomarker for stroke associated infection and future
      mortality in the elderly after an ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Stroke associated infection (within the first seven days)
      occurs in approximately half of stroke patients and is associated with a worse
      prognosis, especially in the elderly. It is uncertain what factors predict stroke
      associated infection, yet identification of a suitable biomarker for infection
      may allow early and appropriate intervention with antibiotics. The aims of this
      study were to: a) identify independent risk factors for stroke associated
      infection, and b) test relationships between these risk factors and mortality at
      2 years. METHODS: Eight-two elderly patients were assessed within 72 h of stroke.
      Data on stroke severity (Barthel Index), stroke associated infection and
      mortality at 2 years were collected. Inflammatory biomarkers at baseline and 6
      months were measured by ELISA. Logistic regression was used to identify risk
      factors for stroke associated infection and death. RESULTS: Patients with stroke
      associated infection, especially pneumonia, had increased IL-6, more severe
      strokes, and higher mortality. IL-6 was independently associated with stroke
      associated infection (OR = 19.2, [95%CI 3.68, 100], p < 0.001), after adjustment
      for other risk factors and cytokines. IL-6 was also independently associated with
      2 year mortality (OR = 9.2, [1.0, 85.1], p = 0.031). CONCLUSIONS: These data
      suggest that IL-6 may be a key biomarker for predicting stroke associated
      infection and mortality in the first two years post stroke.

PMID- 23872301
TI  - Liposomes interiorly thickened with thermosensitive nanogels as novel drug
      delivery systems.
AB  - The fundamental structure of liposomes suffers from drawbacks of physical
      instability. To overcome this problem, the hypothesis of this study was to
      thicken the liposomal interior by incorporating thermosensitive in situ gel. The
      so called gelliposomes (GLs) were prepared by a thin-film method using poloxamer
      solutions as interior aqueous phase. Interior thermosensitive gelation was proved
      by observation of sustained dissolving of the poloxamer gel after destroying the
      lipid bilayers with Triton X-100; structural transformation as observed under
      optical microscopy in a heating-cooling circle also proved the fact of interior
      gelling. The sol-gel transition temperatures of GLs were in good correlation with
      those of the bulk poloxamer solution counterparts, which could be easily tailored
      by adjusting the concentration and ratio of poloxamer 407 (P407) to poloxamer 188
      (P188). Membrane anisotropy measurement indicated increased membrane rigidity. In
      vitro release of the model drug cytosine arabinoside from GLs showed sustained
      release characteristics for at least one week with typical biphasic kinetics.
      Study on storage stability and protection against the destroying effect by
      membrane destroyers indicated improved physical stability in comparison with
      conventional liposomes. In situ evading of phagocytic uptake by macrophages was
      observed for GLs, which however should be attributed to the effect of exteriorly
      adsorbed poloxamers. In conclusion, GLs present distinct characteristics to be
      used as potential drug delivery systems. 

PMID- 23872302
TI  - The effect of capsule-filling machine vibrations on average fill weight.
AB  - The aim of this paper is to study the effect of the speed of capsule filling and
      the inherent machine vibrations on fill weight for a dosator-nozzle machine. The
      results show that increasing speed of capsule filling amplifies the vibration
      intensity (as measured by Laser Doppler vibrometer) of the machine frame, which
      leads to powder densification. The mass of the powder (fill weight) collected via
      the nozzle is significantly larger at a higher capsule filling speed. Therefore,
      there is a correlation between powder densification under more intense vibrations
      and larger fill weights. Quality-by Design of powder based products should
      evaluate the effect of environmental vibrations on material attributes, which in
      turn may affect product quality.

PMID- 23872303
TI  - Detecting phase separation of freeze-dried binary amorphous systems using pair
      wise distribution function and multivariate data analysis.
AB  - The purpose of this study is to investigate the use of multivariate data analysis
      for powder X-ray diffraction-pair-wise distribution function (PXRD-PDF) data to
      detect phase separation in freeze-dried binary amorphous systems. Polymer-polymer
      and polymer-sugar binary systems at various ratios were freeze-dried. All samples
      were analyzed by PXRD, transformed to PDF and analyzed by principal component
      analysis (PCA). These results were validated by differential scanning calorimetry
      (DSC) through characterization of glass transition of the maximally freeze
      concentrate solute (Tg'). Analysis of PXRD-PDF data using PCA provides a more
      clear 'miscible' or 'phase separated' interpretation through the distribution
      pattern of samples on a score plot presentation compared to residual plot method.
      In a phase separated system, samples were found to be evenly distributed around
      the theoretical PDF profile. For systems that were miscible, a clear deviation of
      samples away from the theoretical PDF profile was observed. Moreover, PCA
      analysis allows simultaneous analysis of replicate samples. Comparatively, the
      phase behavior analysis from PXRD-PDF-PCA method was in agreement with the DSC
      results. Overall, the combined PXRD-PDF-PCA approach improves the clarity of the
      PXRD-PDF results and can be used as an alternative explorative data analytical
      tool in detecting phase separation in freeze-dried binary amorphous systems.

PMID- 23872304
TI  - Piezo1 plays a role in erythrocyte volume homeostasis.
AB  - Mechanosensitivity is an inherent property of virtually all cell types, allowing
      them to sense and respond to physical environmental stimuli. Stretch-activated
      ion channels represent a class of mechanosensitive proteins which allow cells to
      respond rapidly to changes in membrane tension; however their identity has
      remained elusive. The piezo genes have recently been identified as a family of
      stretch-activated mechanosensitive ion channels. We set out to determine the role
      of piezo1 during zebrafish development. Here we report that morpholino-mediated
      knockdown of piezo1 impairs erythrocyte survival without affecting hematopoiesis
      or differentiation. Our results demonstrate that piezo1 is involved in
      erythrocyte volume homeostasis, disruption of which results in swelling/lysis of
      red blood cells and consequent anemia. 

PMID- 23872305
TI  - NUP214-ABL1-mediated cell proliferation in T-cell acute lymphoblastic leukemia is
      dependent on the LCK kinase and various interacting proteins.
AB  - The NUP214-ABL1 fusion protein is a constitutively active protein tyrosine kinase
      that is found in 6% of patients with T-cell acute lymphoblastic leukemia and that
      promotes proliferation and survival of T-lymphoblasts. Although NUP214-ABL1 is
      sensitive to ABL1 kinase inhibitors, development of resistance to these compounds
      is a major clinical problem, underlining the need for additional drug targets in
      the sparsely studied NUP214-ABL1 signaling network. In this work, we identify and
      validate the SRC family kinase LCK as a protein whose activity is absolutely
      required for the proliferation and survival of T-cell acute lymphoblastic
      leukemia cells that depend on NUP214-ABL1 activity. These findings underscore the
      potential of SRC kinase inhibitors and of the dual ABL1/SRC kinase inhibitors
      dasatinib and bosutinib for the treatment of NUP214-ABL1-positive T-cell acute
      lymphoblastic leukemia. In addition, we used mass spectrometry to identify
      protein interaction partners of NUP214-ABL1. Our results strongly support that
      the signaling network of NUP214-ABL1 is distinct from that previously reported
      for BCR-ABL1. Moreover, we found that three NUP214-ABL1-interacting proteins,
      MAD2L1, NUP155, and SMC4, are strictly required for the proliferation and
      survival of NUP214-ABL1-positive T-cell acute lymphoblastic leukemia cells. In
      conclusion, this work identifies LCK, MAD2L1, NUP155 and SMC4 as four new
      potential drug targets in NUP214-ABL1-positive T-cell acute lymphoblastic
      leukemia. 

PMID- 23872306
TI  - STAT3 mutations identified in human hematologic neoplasms induce myeloid
      malignancies in a mouse bone marrow transplantation model.
AB  - STAT3 protein phosphorylation is a frequent event in various hematologic
      malignancies and solid tumors. Acquired STAT3 mutations have been recently
      identified in 40% of patients with T-cell large granular lymphocytic leukemia, a
      rare T-cell disorder. In this study, we investigated the mutational status of
      STAT3 in a large series of patients with lymphoid and myeloid diseases. STAT3
      mutations were identified in 1.6% (4 of 258) of patients with T-cell neoplasms,
      in 2.5% (2 of 79) of patients with diffuse large B-cell lymphoma but in no other
      B-cell lymphoma patients (0 of 104) or patients with myeloid malignancies (0 of
      96). Functional in vitro assays indicated that the STAT3Y640F mutation leads to a
      constitutive phosphorylation of the protein. STA21, a STAT3 small molecule
      inhibitor, inhibited the proliferation of two distinct STAT3 mutated cell lines.
      Using a mouse bone marrow transplantation assay, we observed that STAT3Y640F
      expression leads to the development of myeloproliferative neoplasms with
      expansion of either myeloid cells or megakaryocytes. Together, these data
      indicate that the STAT3Y640F mutation leads to constitutive activation of STAT3,
      induces malignant hematopoiesis in vivo, and may represent a novel therapeutic
      target in some lymphoid malignancies. 

PMID- 23872307
TI  - Activated factor X signaling via protease-activated receptor 2 suppresses pro
      inflammatory cytokine production from lipopolysaccharide-stimulated myeloid
      cells.
AB  - Vitamin K-dependent proteases generated in response to vascular injury and
      infection enable fibrin clot formation, but also trigger distinct immuno
      regulatory signaling pathways on myeloid cells. Factor Xa, a protease crucial for
      blood coagulation, also induces protease-activated, receptor-dependent cell
      signaling. Factor Xa can bind both monocytes and macrophages, but whether factor
      Xa-dependent signaling stimulates or suppresses myeloid cell cytokine production
      in response to Toll-like receptor activation is not known. In this study,
      exposure to factor Xa significantly impaired pro-inflammatory cytokine production
      from lipopolysaccharide-treated peripheral blood mononuclear cells, THP-1
      monocytic cells and murine macrophages. Furthermore, factor Xa inhibited nuclear
      factor-kappa B activation in THP-1 reporter cells, requiring
      phosphatidylinositide 3-kinase activity for its anti-inflammatory effect. Active
      site blockade, gamma-carboxyglutamic acid domain truncation and a peptide mimic
      of the factor Xa inter-epidermal growth factor-like region prevented factor Xa
      inhibition of lipopolysaccharide-induced tumor necrosis factor-alpha release. In
      addition, factor Xa anti-inflammatory activity was markedly attenuated by the
      presence of an antagonist of protease-activated receptor 2, but not protease
      activated receptor 1. The key role of protease-activated receptor 2 in eliciting
      factor Xa-dependent anti-inflammatory signaling on macrophages was further
      underscored by the inability of factor Xa to mediate inhibition of tumor necrosis
      factor-alpha and interleukin-6 release from murine bone marrow-derived protease
      activated receptor 2-deficient macrophages. We also show for the first time that,
      in addition to protease-activated receptor 2, factor Xa requires a receptor
      associated protein-sensitive low-density lipoprotein receptor to inhibit
      lipopolysaccharide-induced cytokine production. Collectively, the findings of
      this study support a novel function for factor Xa as an endogenous, receptor
      associated protein-sensitive, protease-activated receptor 2-dependent regulator
      of myeloid cell pro-inflammatory cytokine production. 

PMID- 23872308
TI  - Circulating clonotypic B cells in multiple myeloma and monoclonal gammopathy of
      undetermined significance.
AB  - The B-cell compartment in which multiple myeloma stem cells reside remains
      unclear. We investigated the potential presence of mature, surface-membrane
      immunoglobulin-positive B lymphocytes clonally related to the tumor bone marrow
      plasma cells among different subsets of peripheral blood B cells from ten
      patients (7 with multiple myeloma and 3 with monoclonal gammopathies of
      undetermined significance). The presence of clonotypic immunoglobulin heavy chain
      gene rearrangements was determined in multiple highly-purified fractions of
      peripheral blood B-lymphocytes including surface-membrane IgM(+) CD27(-) naive B
      lymphocytes, plus surface-membrane IgG(+), IgA(+) and IgM(+) memory CD27(+) B
      cells, and normal circulating plasma cells, in addition to (mono)clonal plasma
      cells, by a highly-specific and sensitive allele-specific oligonucleotide
      polymerase chain reaction directed to the CDR3 sequence of the rearranged IGH
      gene of tumor plasma cells from individual patients. Our results showed
      systematic absence of clonotypic rearrangements in all the different B-cell
      subsets analyzed, including M-component isotype-matched memory B-lymphocytes, at
      frequencies <0.03 cells/MUL (range: 0.0003-0.08 cells/MUL); the only exception
      were the myeloma plasma cells detected and purified from the peripheral blood of
      four of the seven myeloma patients. These results indicate that circulating B
      cells from patients with multiple myeloma and monoclonal gammopathies of
      undetermined significance are usually devoid of clonotypic B cells while the
      presence of immunophenotypically aberrant myeloma plasma cells in peripheral
      blood of myeloma patients is a relatively frequent finding. 

PMID- 23872310
TI  - In vivo activation of the human delta-globin gene: the therapeutic potential in
      beta-thalassemic mice.
AB  - beta-thalassemia and sickle cell disease are widespread fatal genetic diseases.
      None of the existing clinical treatments provides a solution for all patients.
      Two main strategies for treatment are currently being investigated: (i) gene
      transfer of a normal beta-globin gene; (ii) reactivation of the endogenous gamma
      globin gene. To date, neither approach has led to a satisfactory, commonly
      accepted standard of care. The delta-globin gene produces the delta-globin of
      hemoglobin A2. Although expressed at a low level, hemoglobin A2 is fully
      functional and could be a valid substitute of hemoglobin A in beta-thalassemia,
      as well as an anti-sickling agent in sickle cell disease. Previous in vitro
      results suggested the feasibility of transcriptional activation of the human
      delta-globin gene promoter by inserting a Kruppel-like factor 1 binding site. We
      evaluated the activation of the Kruppel-like factor 1 containing delta-globin
      gene in vivo in transgenic mice. To evaluate the therapeutic potential we crossed
      the transgenic mice carrying a single copy activated delta-globin gene with a
      mouse model of beta-thalassemia intermedia. We show that the human delta-globin
      gene can be activated in vivo in a stage- and tissue-specific fashion simply by
      the insertion of a Kruppel-like factor 1 binding site into the promoter. In
      addition the activated delta-globin gene gives rise to a robust increase of the
      hemoglobin level in beta-thalassemic mice, effectively improving the thalassemia
      phenotype. These results demonstrate, for the first time, the therapeutic
      potential of the delta-globin gene for treating severe hemoglobin disorders which
      could lead to novel approaches, not involving gene addition or reactivation, to
      the cure of beta-hemoglobinopathies. 

PMID- 23872309
TI  - Comprehensive whole-genome sequencing of an early-stage primary myelofibrosis
      patient defines low mutational burden and non-recurrent candidate genes.
AB  - In order to identify novel somatic mutations associated with classic BCR/ABL1
      negative myeloproliferative neoplasms, we performed high-coverage genome
      sequencing of DNA from peripheral blood granulocytes and cultured skin
      fibroblasts from a patient with MPL W515K-positive primary myelofibrosis. The
      primary myelofibrosis genome had a low somatic mutation rate, consistent with
      that observed in similar hematopoietic tumor genomes. Interfacing of whole-genome
      DNA sequence data with RNA expression data identified three somatic mutations of
      potential functional significance: i) a nonsense mutation in CARD6, implicated in
      modulation of NF-kappaB activation; ii) a 19-base pair deletion involving a
      potential regulatory region in the 5'-untranslated region of BRD2, implicated in
      transcriptional regulation and cell cycle control; and iii) a non-synonymous
      point mutation in KIAA0355, an uncharacterized protein. Additional mutations in
      three genes (CAP2, SOX30, and MFRP) were also evident, albeit with no support for
      expression at the RNA level. Re-sequencing of these six genes in 178 patients
      with polycythemia vera, essential thrombocythemia, and myelofibrosis did not
      identify recurrent somatic mutations in these genes. Finally, we describe methods
      for reducing false-positive variant calls in the analysis of hematologic
      malignancies with a low somatic mutation rate. This trial is registered with
      ClinicalTrials.gov (NCT01108159). 

PMID- 23872311
TI  - Whiplash disorder--is it a valid disease definition?

PMID- 23872312
TI  - Sandfly-borne phleboviruses of Eurasia and Africa: epidemiology, genetic
      diversity, geographic range, control measures.
AB  - Sandfly-borne phleboviruses may cause a transient febrile illness (sandfly fever)
      or more severe neuroinvasive disease. In the Old World, they are vectored by
      phlebotomine flies, which are widely distributed in the Mediterranean basin,
      North Africa, the Indian subcontinent, the Middle East and central Asia. High
      seroprevalence rates have been recorded in humans and domestic animals in areas
      where sandflies are present. Most published studies have focused on phlebovirus
      infections of travelers and of soldiers stationed in endemic areas, but the
      health impact on local populations should not be underestimated, as
      seroprevalence studies indicate massive circulation of these viruses, even if
      disease is seldom documented. Except for Toscana virus, which shows a marked
      neurotropism and is a leading cause of aseptic meningitis in endemic regions,
      phlebovirus infections are inadequately considered by physicians and are
      generally underestimated. However, several properties of these viruses suggest
      that they will extend their geographic range. First, changes in the areas
      occupied by sandflies as a result of climate change have a direct impact on the
      epidemiology of associated human and animal diseases. Second, phleboviruses
      exhibit a high mutation rate, and their tri-segmented genome is prone to
      reassortment and recombination. Third, distinct virus strains can be transmitted
      by the same arthropod species. Recent studies have documented the distribution of
      sandfly-borne phleboviruses in Western Europe, but data for Eastern Europe, the
      Middle East and Africa are very limited. With the goal of filling knowledge gaps
      and planning new research programs, we have examined available information and
      present it as a comprehensive review, with a specific focus on understudied
      regions. We also discuss the need to conduct studies aimed at developing new
      antiviral drugs and vaccines. 

PMID- 23872315
TI  - Introduction to the ECR special issue on the roles of small GTPases.

PMID- 23872314
TI  - Numb modulates the paracellular permeability of intestinal epithelial cells
      through regulating apical junctional complex assembly and myosin light chain
      phosphorylation.
AB  - Numb is highly expressed throughout the crypt-villus axis of intestinal mucosa
      and functions as cell fate determinant and integrator of cell-to-cell adhesion.
      Increased paracellular permeability of intestinal epithelial cells is associated
      with the epithelial barrier dysfunction of inflammatory bowel diseases (IBDs).
      The apical junctional complex (AJC) assembly and myosin light chain (MLC)
      phosphorylation regulate adherens junctions (AJ) and tight junctions (TJ). We
      determined whether and how Numb modulate the paracellular permeability of
      intestinal epithelial cells. Caco-2 intestinal epithelial cells and their Numb
      interfered counterparts were used in the study for physiological, morphological
      and biological analyses. Numb, expressed in intestinal epithelial cells and
      located at the plasma membrane of Caco-2 cells in a basolateral to apical
      distribution, increased in the intestinal epithelial cells with the formation of
      the intestinal epithelial barrier. Numb expression decreased and accumulated in
      the cytoplasm of intestinal epithelial cells in a DSS-induced colitis mouse
      model. Numb co-localized with E-cadherin, ZO-1 and Par3 at the plasma membrane
      and interacted with E-cadherin and Par3. Knockdown of Numb in Caco-2 cells
      altered the F-actin structure during the Ca(2+) switch assay, enhanced TNFalpha
      /INF-gamma-induced intestinal epithelial barrier dysfunction and TJ destruction,
      and increased the Claudin-2 protein level. Immunofluorescence experiments
      revealed that NMIIA and F-actin co-localized at the cell surface of Caco-2 cells.
      Numb knockdown in Caco-2 cells increased F-actin contraction and the abundance of
      phosphorylated MLC. Numb modulated the intestinal epithelial barrier in a Notch
      signaling-independent manner. These findings suggest that Numb modulates the
      paracellular permeability by affecting AJC assembly and MLC phosphorylation. 

PMID- 23872313
TI  - Crimean-Congo hemorrhagic fever in Iran.
AB  - The presence of Crimean-Congo hemorrhagic fever virus (CCHFV) in Iran was first
      identified in studies of livestock sera and ticks in the 1970s, but the first
      human infection was not diagnosed until 1999. Since that time, the number of
      cases of CCHF in Iran has markedly increased. Through January 2012, articles in
      the published literature have reported a total of 870 confirmed cases, with 126
      deaths, for a case fatality rate (CFR) of 17.6%. The disease has been seen in 26
      of the country's 31 provinces, with the greatest number of cases in Sistan and
      Baluchestan, Isfahan, Fars, Tehran, Khorasan, and Khuzestan provinces. The
      increase in CCHF in Iran has paralleled that in neighboring Turkey, though the
      number of cases in Turkey has been much larger, with an overall CFR of around 5%.
      In this article, we review the features of CCHF in Iran, including its history,
      epidemiology, animal and tick reservoirs, current surveillance and control
      programs, diagnostic methods, clinical features and experience with ribavirin
      therapy, and consider possible explanations for the difference in the CFR of CCHF
      between Iran and Turkey. The emergence of CCHF in Iran calls for countermeasures
      at many levels to protect the population, but also provides opportunities for
      studying the epidemiology, diagnosis and management of the disease. 

PMID- 23872316
TI  - Chorion formation in panoistic ovaries requires windei and trimethylation of
      histone 3 lysine 9.
AB  - Epigenetic modifications play key roles in transcriptional regulation.
      Trimethylation of histone 3 lysine 9 (H3K9me3) is one of the most widely studied
      histone post-translational modifications, and has been linked to transcriptional
      repression. In Drosophila melanogaster, Windei is needed for H3K9me3 in female
      germ line cells. Here, we report the occurrence of a D. melanogaster Windei (Wde)
      ortholog in the ovary of the hemimetabolous insect Blattella germanica, which we
      named BgWde. Depletion of BgWde by RNAi reduced H3K9me3 in follicular cells,
      which triggered changes in transcriptional regulation that led to the prevention
      of chorion gene expression. In turn, this impaired oviposition (and the formation
      of the ootheca) and, therefore, prevented reproduction. Windei and H3K9me3 have
      already been reported in follicular cells of D. melanogaster, but this is the
      first time that the function of these modifications has been demonstrated in the
      said cells. This is also the first time that an epigenetic marker is reported as
      having a key role in choriogenesis.

PMID- 23872317
TI  - Suitability of scoring PCC rings and fragments for dose assessment after high
      dose exposures to ionizing radiation.
AB  - Assessment of radiation doses through measurement of dicentric chromosomes may be
      difficult due to the inability of damaged cells to reach mitosis. After high-dose
      exposures, premature chromosome condensation (PCC) has become an important method
      in biodosimetry. PCC can be induced upon fusion with mitotic cells, or by
      treatment with chemicals such as calyculin A or okadaic acid. Several different
      cytogenetic endpoints have been measured with chemically induced PCC, e.g., via
      scoring of extra chromosome pieces or ring chromosomes. The dose-effect curves
      published with chemically induced PCC show differences in their coefficients and
      in the distribution of rings among cells. Here we present a study with calyculin
      A to induce PCC in peripheral blood lymphocytes irradiated at nine different
      doses of gamma-rays up to 20Gy. Colcemid was also added in order to observe
      metaphase cells. During microscopical analysis the chromosome aberrations
      observed in the different cell-cycle phases (G2/M-PCC, M/A-PCC and M cells) were
      recorded. The proportion of G2/M-PCC cells was predominant from 3 to 20Gy, M
      cells decreased above 1Gy and M/A-PCC cells remained constant at all doses and
      showed the highest frequencies of PCC rings. Depending on the cell-cycle phase
      there was a difference in the linear coefficients in the dose-effect curves of
      extra fragments and rings. Poisson distribution among PCC rings was observed
      after calyculin A+colcemid treatment, facilitating the use of this methodology
      also for partial body exposures to high doses. This has been tested with two
      simulated partial exposures to 6 and 12Gy. The estimated doses in the irradiated
      fraction were very close to the real dose, indicating the usefulness of this
      methodology.

PMID- 23872318
TI  - Wing (Ib) cells in frog taste discs detect dietary unsaturated fatty acids.
AB  - The effects of unsaturated fatty acids on membrane properties were studied using
      conventional whole-cell patch-clamp recording of isolated wing (Ib) cells in
      bullfrog (Lithobates catesbeianus) taste discs. Applying arachidonic acid to the
      bath induced monophasic inward currents in 60% of wing cells and biphasic inward
      and outward currents in the other cells. The intracellular dialysis of
      arachidonic acid did not induce an inward current; however, it enhanced a slowly
      developing Ba(2+)-sensitive outward current. The effects of various unsaturated
      fatty acids were explored under the condition of Cs(+) internal solution.
      Linoleic and alpha-linolenic acids induced large inward currents. Oleic,
      eicosapentaenoic and docosahexaenoic acids elicited the same inward currents as
      those of arachidonic acid. Wing cells, under the basal condition with Cs(+)
      internal solution, displayed a small inward current of -1.1+/-0.1pA/pF at -50mV
      (n=40), in which the peak existed at a membrane potential of -49mV. Removing
      external Ca(2+) further increased the inward current by -2.9+/-0.3pA/pF at -50mV
      (n=4) from the basal current and the peak was located at -55mV. External linoleic
      acid (50MUM) also induced a similar inward current of -5.6+/-0.6pA/pF at -50mV
      (n=19) from the basal current and the peak was located at -61mV. External Ca(2+)
      free saline and linoleic acid induced similar current/voltage (I/V) relationships
      elicited by a ramp voltage as well as voltage steps. Linoleic acid-induced
      currents were not influenced by replacing internal EGTA with BAPTA, whereas
      inward currents disappeared under the elimination of external Na(+) and addition
      of flufenamic acid. These results suggest that dietary unsaturated fatty acids
      may depolarize wing (Ib) cells, which affects the excitability of these cells. 

PMID- 23872319
TI  - Effects of carotenoid and vitamin E supplementation on oxidative stress and
      plumage coloration in house finches (Haemorhous mexicanus).
AB  - There has been much recent interest from both applied and basic scientists in the
      broad series of benefits that animals reap from acquiring high concentrations of
      dietary antioxidants, such as carotenoids and vitamins (e.g., vitamin E, or
      tocopherol). Most attention has been paid to separate effects of these compounds
      on, for example, coloration, health state, development, and vision, but because
      of possible interactions between these lipid-soluble molecules, we are in need of
      more studies that co-manipulate these substances and examine their possible
      synergistic impacts on animal physiology and phenotype. We capitalized on a model
      avian system (the house finch, Haemorhous mexicanus), where extensive information
      is available on the fitness roles of carotenoids, to test how variation in
      carotenoid and/or vitamin E concentrations in the diet impacts body accumulation
      of these compounds, factors related to oxidative damage (e.g., breast muscle and
      plasma oxidative-stress susceptibility, plasma nitric-oxide levels), and plumage
      color development. As in a previous study of ours on carotenoids and health in
      finches, we employed a 2*2 factorial experimental design on birds in both molting
      and non-molting conditions, to understand how seasonal shifts in carotenoid use
      (i.e., pigment incorporation into plumage) might alter the accumulation and roles
      of carotenoids and vitamins. As expected, lutein supplementation increased the
      level of circulating carotenoids in both experiments and the color of newly
      molted plumage. By contrast, vitamin E provisioning did not significantly affect
      plasma carotenoid levels or plumage coloration in either experiment.
      Interestingly, carotenoid provisioning decreased circulating vitamin E levels
      during molt, which suggests either molecular competition between carotenoids and
      tocopherol at the absorption/transport stages or that vitamin E serves as an
      antioxidant to offset harmful actions that carotenoids may have at very high
      concentrations. Finally, in both experiments, we found a reduction in breast
      muscle oxidative damage for tocopherol-supplemented birds, which constitutes the
      first demonstration of a protective effect of vitamin E against oxidative stress
      in wild birds. Taken together, these findings provide an interesting contrast
      with our earlier work on season-specific physiological benefits of carotenoids in
      finches and point to complex associations between indicators of antioxidant and
      oxidative state in wild-caught animals. 

PMID- 23872320
TI  - Postprandial response and tissue distribution of the bile acid synthesis-related
      genes, cyp7a1, cyp8b1 and shp, in rainbow trout Oncorhynchus mykiss.
AB  - In mammals, cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha
      hydroxylase (CYP8B1) are rate-limiting enzymes in bile acid synthesis. In
      addition, a small heterodimer partner (SHP) is also known to inhibit bile acid
      synthesis via the suppression of CYP7A1 and CYP8B1 expression. However, little
      information is currently available regarding primary structure of the genes
      involved in bile acid synthesis in fish. We therefore cloned cyp7a1, cyp8b1 and
      shp genes from rainbow trout and obtained cDNAs encoding two isoforms each of
      Cyp7a1 (-1 and -2), Cyp8b1 (-1 and -2) and Shp (-1 and -2). Both cyp7a1-1 and -2
      encoded proteins of 512 amino acids. Trout cyp7a1-1 was expressed not only
      primarily in the kidney, pyloric caecum and mid-gut, but also weakly in the
      liver, eye, gill and ovary. cyp7a1-2 was highly expressed in the liver, pyloric
      caecum and mid-gut. cyp8b1-1 and -2, which encoded proteins of 512 and 509 amino
      acids, respectively, were principally expressed in the liver. Both shp-1 and -2,
      which encoded proteins of 288 and 290 amino acids, respectively, were strongly
      expressed in the liver, but shp-2 was also highly expressed in the gallbladder
      and digestive tract. The temporal changes in the expression of cyp7a1-1/-2,
      cyp8b1-1/-2 and shp-1/-2 in the liver were assessed after consumption of a single
      meal. Expression of cyp7a1-1/-2 and cyp8b1-1/-2 increased within 3h post feeding
      (hpf) when the stomach was still approximately 84% full and the gallbladder was
      almost completely empty. Although the expression of shp-1 did not change after
      feeding, the expression pattern of shp-2 was inversely related to the expression
      patterns of cyp7a1-1/-2 and cyp8b1-1/-2. Specifically, shp-2 expression decreased
      until 3 hpf before returning to initial levels at 24 hpf. These findings suggest
      that Cyp7a1s/8b1s and Shp-2 function antagonistically in bile acid synthesis in
      rainbow trout. 

PMID- 23872321
TI  - Development and application of a novel reverse transcription real-time PCR method
      for miR-499 quantification.
AB  - OBJECTIVES: MicroRNAs (miRNAs) are endogenous small RNAs of 21-25 nucleotides
      that can pair with sites in 3' untranslated regions in mRNAs of protein-coding
      genes to downregulate their expression. Recently, miR-499 and other miRNAs
      released in circulating blood have been reported as promising biomarkers for
      acute myocardial infarction (AMI). In the present study, we developed a novel
      reverse-transcription real-time PCR assay for human miR-499 quantification.
      DESIGN AND METHODS: miR-499 was reverse-transcribed with a 3' portion-specific
      primer into cDNAs. The cDNAs were further extended with overlap PCR. The extended
      cDNAs were determined by quantitative, real-time PCR. Synthetic miR-499 was put
      into the RT reaction over an optimal range to generate standard curves for
      absolute quantification of miR-499. RESULTS: In the presence of 0.0001 amol/MUL
      to 1.0*106 amol/MUL of synthetic miR-499, we observed a linear correlation
      (R2=0.999) between the logarithm of the amount of input RNA and the CT value. The
      miR-499 was reliably measured at a detection limit of 0.0001 amol/MUL. The miR
      499 measurements in spiked plasma samples indicated excellent correlation between
      the novel qRT PCR and classic stem loop qRT PCR. The qRT PCR analysis
      demonstrated that miR-499 was detected with higher levels in plasma from the
      patient with AMI in acute phase (AMI) compared with those from the control groups
      (P<0.001). CONCLUSIONS: We developed a novel reverse-transcription real-time PCR
      assay for human miR-499 quantification. The good reproducibility and wide
      linearity range may permit more use of it in the quantification of other human
      miRNAs in future.

PMID- 23872322
TI  - Aptasensor and genosensor methods for detection of microbes in real world
      samples.
AB  - The increasing concerns about food and environmental safety have prompted the
      desire to develop rapid, specific, robust and highly sensitive methods for the
      detection of microorganisms to ensure public health. Although traditional
      microbiological methods are available, they are labor intensive, unsuitable for
      on-site and high throughput analysis, and need well-trained personnel. To
      circumvent these drawbacks, many efforts have been devoted towards the
      development of biosensors, using nucleic acid as bio-recognition element. In this
      review, we will focus on recent significant advances made in two types of DNA
      based biosensors, namely genosensors, and aptasensors. In genosensor approach,
      DNA or RNA target is detected through the hybridization reaction between DNA or
      RNA and ssDNA sensing element, while in aptasensor method, DNA or RNA aptamer,
      capable of binding to a target molecule with high affinity and specificity, plays
      the role of receptor. The goal of this article is to review the innovative
      methods that have been emerged in genosensor and aptasensor during recent years.
      Particular attention is given to recent advances and trends in selection of
      biorecognition element, DNA immobilization strategies and sensing formats.

PMID- 23872323
TI  - Single color FRET based measurements of conformational changes of proteins
      resulting from translocation inside cells.
AB  - Translocation of proteins to different parts of the cell is necessary for many
      cellular mechanisms as a means for regulation and a variety of other functions.
      Identifying how these proteins undergo conformational changes or interact with
      various partners during these events is critical to understanding how these
      mechanisms are executed. A protocol is presented that identifies conformational
      changes in a protein that occur during translocation while overcoming challenges
      in extracting distance information in very different environments of a living
      cell. Only two samples are required to be prepared and are observed with one
      optical setup. Live-cell FRET imaging has been applied to identify conformational
      changes between two native cysteines in Bax, a member of the Bcl-2 family of
      proteins that regulates apoptosis. Bax exists in the cytosol and translocates to
      the mitochondria outer membrane upon apoptosis induction. The distance, r,
      between the two native cysteines in the cytosolic structure of Bax necessitates
      the use of a FRET donor-accepter pair with R0~r as the most sensitive probe for
      identifying structural changes at these positions. Alexa Fluor 546 and Dabcyl, a
      dark acceptor, were used as FRET pairs - resulting in single color intensity
      variations of Alexa-546 as a measure of FRET efficiency. An internal reference,
      conjugated to Bax, was employed to normalize changes in fluorescence intensity of
      Alexa Fluor 546 due to inherent inhomogeneities in the living cell. This
      correction allowed the true FRET effects to be measured with increased precision
      during translocation. Normalization of intensities to the internal reference
      identified a FRET efficiency of 0.45+/-0.14 in the cytosol and 0.11+/-0.20 in the
      mitochondria. The procedure for the conjugation of the internal reference and
      FRET probes as well as the data analysis is presented. 

PMID- 23872324
TI  - Understanding the role of cross-arm binding efficiency in the activity of
      monoclonal and multispecific therapeutic antibodies.
AB  - Antibodies are essential components of the adaptive immune system that provide
      protection from extracellular pathogens and aberrant cells in the host.
      Immunoglobulins G, which have been adapted for therapeutic use due to their
      exquisite specificity of target recognition, are bivalent homodimers composed of
      two antigen binding Fab arms and an immune cell recruiting Fc module. In recent
      years significant progress has been made in optimizing properties of both Fab and
      Fc components to derive antibodies with improved affinity, stability, and
      effector function. However, systematic analyses of the efficiency with which
      antibodies crosslink their targets have lagged, despite the well-recognized
      importance of this cross-arm binding for optimal antigen engagement. Such an
      understanding is particularly relevant given the variety of next-generation
      multispecific antibody scaffolds under development. In this manuscript we attempt
      to fill this gap by presenting a framework for analysis and optimization of
      antibody cross-arm engagement. We illustrate the power of this integrated
      approach by presenting case studies for rational multispecific antibody design
      based on quantitative assessment of the interplay between antibody valency,
      target expression, and cross-arm binding efficiency. We conclude that optimal
      design parameters for cross-arm binding strongly depend on the biological context
      of the disease, and that cross-arm binding efficiency needs to be considered for
      successful application of multispecific antibodies. 

PMID- 23872325
TI  - The European heart journal launches ethics review board.

PMID- 23872327
TI  - Illicium verum extract suppresses IFN-gamma-induced ICAM-1 expression via
      blockade of JAK/STAT pathway in HaCaT human keratinocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Interferon-gamma (IFN-gamma) signaling in
      keratinocytes plays an important role in mediating inflammatory conditions such
      as psoriasis and contact dermatitis. Illicium verum Hook. f. has been used in
      traditional medicine for treating skin inflammation, rheumatism, asthma, and
      bronchitis in Asia. AIM OF THE STUDY: To investigate the anti-inflammatory
      effects and regulatory mechanisms of Illicium verum extract (IVE) in the human
      keratinocyte cell line HaCaT. MATERIALS AND METHODS: In this study, we examined
      the effect of IVE on IFN-gamma-induced ICAM-1 expression in HaCaT cells. The
      levels of IFN-gamma receptor alpha (IFN-gammaRalpha), phosphorylated Janus kinase
      2 (pJak2), phosphorylated signal transducer and activator of transcription 1
      (pSTAT1), and suppressor of cytokine signaling 1 (SOCS1) were analyzed by western
      blot. Expression of intercellular adhesion molecule-1 (ICAM-1) on the HaCaT cells
      was determined by reverse transcription-polymerase chain reaction, western blot,
      and cell-surface enzyme-linked immunosorbent assay. The effects of IVE and its
      constituents on the adherence of T lymphocytes to IFN-gamma-treated HaCaT cells
      were also investigated. RESULTS: IVE significantly inhibited IFN-gamma-induced
      mRNA and protein expression of ICAM-1. IVE inhibited IFN-gamma-induced IFN
      gammaRalpha, pJak2 and pSTAT1 expression in HaCaT cells. The expression of SOCS1
      was up-regulated by treatment of IVE. In addition, IVE and its constituents (p
      anisaldehyde and trans-anethole) effectively suppressed IFN-gamma-induced
      adherence of Jurkat T cells to HaCaT cells and ICAM-1 expression on the cell
      surface. CONCLUSIONS: These results indicate that the anti-inflammatory effects
      of IVE may contribute to therapeutic efficacy in IFN-gamma-dependent inflammatory
      skin diseases by modulating the IFN-gamma signal pathway.

PMID- 23872326
TI  - Hippocampal and subicular efferents and afferents of the perirhinal, postrhinal,
      and entorhinal cortices of the rat.
AB  - Available evidence suggests there is functional differentiation among hippocampal
      and parahippocampal subregions and along the dorsoventral (septotemporal) axis of
      the hippocampus. The aim of this study was to characterize and compare the
      efferent and afferent connections of perirhinal areas 35 and 36, postrhinal
      cortex, and the lateral and medial entorhinal areas (LEA and MEA) with dorsal and
      ventral components of the hippocampal formation (dentate gyrus, hippocampus cornu
      ammonis fields, and subiculum) as well as the presubiculum, and the
      parasubiculum. The entorhinal connections were also characterized with respect to
      the LEA and MEA dentate gyrus-projecting bands. In general, the entorhinal
      connections with the hippocampal formation are much stronger than the perirhinal
      and postrhinal connections. The entorhinal cortex projects strongly to all
      components of the hippocampal formation, whereas the perirhinal and postrhinal
      cortices project weakly and only to CA1 and the subiculum. In addition, the
      postrhinal cortex preferentially targets the dorsal CA1 and subiculum, whereas
      the perirhinal cortex targets ventral subiculum. Similarly, the perirhinal cortex
      receives more input from ventral hippocampal formation structures and the
      postrhinal cortex receives more input from dorsal hippocampal structures. The LEA
      and the MEA medial band are more strongly interconnected with ventral hippocampal
      structures, whereas the MEA lateral band is more interconnected with dorsal
      hippocampal structures. With regard to the presubiculum and parasubiculum, the
      postrhinal cortex and the MEA lateral band receive stronger input from the dorsal
      presubiculum and caudal parasubiculum. In contrast, the LEA and MEA medial bands
      receive stronger input from the ventral presubiculum and rostral parasubiculum. 

PMID- 23872328
TI  - Structure and gene cluster of the O-antigen of Escherichia coli O154.
AB  - The O-polysaccharide (O-antigen) of Escherichia coli O154 was studied by sugar
      analysis along with 1D and 2D (1)H and (13)C NMR spectroscopy. The following
      structure of the branched pentasaccharide repeating unit was established:
      [structure: see text]. The O-antigen gene cluster of E. coli O154 was sequenced.
      The gene functions were tentatively assigned by comparison with sequences in the
      available databases and found to be in full agreement with the O-polysaccharide
      structure.

PMID- 23872329
TI  - Efficient microwave assisted synthesis of novel 1,2,3-triazole-sucrose
      derivatives by cycloaddition reaction of sucrose azides and terminal alkynes.
AB  - Novel 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-substituted
      1,2,3-triazoles were synthesized by microwave assisted copper catalyzed 1,3
      dipolar cycloaddition of sucrose derived azides with terminal alkynes in
      excellent yields and in short reaction times. The compound 1',2,3,3',4,4',6-hepta
      O-acetyl-6'-azido-6'-deoxy-sucrose was regioselectively synthesized from sucrose
      by improved procedure and used for the cycloadditions. By combining carbohydrate
      and 1,2,3-triazole structural motifs, a library of 1,2,3-triazole-sucrose
      conjugates have been obtained. 

PMID- 23872330
TI  - The N-BAR domain protein, Bin3, regulates Rac1- and Cdc42-dependent processes in
      myogenesis.
AB  - Actin dynamics are necessary at multiple steps in the formation of multinucleated
      muscle cells. BAR domain proteins can regulate actin dynamics in several cell
      types, but have been little studied in skeletal muscle. Here, we identify novel
      functions for the N-BAR domain protein, Bridging integrator 3 (Bin3), during
      myogenesis in mice. Bin3 plays an important role in regulating myofiber size in
      vitro and in vivo. During early myogenesis, Bin3 promotes migration of
      differentiated muscle cells, where it colocalizes with F-actin in lamellipodia.
      In addition, Bin3 forms a complex with Rac1 and Cdc42, Rho GTPases involved in
      actin polymerization, which are known to be essential for myotube formation.
      Importantly, a Bin3-dependent pathway is a major regulator of Rac1 and Cdc42
      activity in differentiated muscle cells. Overall, these data classify N-BAR
      domain proteins as novel regulators of actin-dependent processes in myogenesis,
      and further implicate BAR domain proteins in muscle growth and repair.

PMID- 23872332
TI  - Somatostatin receptors: from signaling to clinical practice.
AB  - Somatostatin is a peptide with a potent and broad antisecretory action, which
      makes it an invaluable drug target for the pharmacological management of
      pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A
      and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a
      wide expression pattern in both normal tissues and solid tumors. Investigating
      the function of each SSTR in several tumor types has provided a wealth of
      information about the common but also distinct signaling cascades that suppress
      tumor cell proliferation, survival and angiogenesis. This provided the rationale
      for developing multireceptor-targeted somatostatin analogs and combination
      therapies with signaling-targeted agents such as inhibitors of the mammalian (or
      mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and
      the development of rabiolabeled somatostatin analogs have improved the diagnosis
      and treatment of neuroendocrine tumors. 

PMID- 23872331
TI  - Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin,
      neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot
      flushes.
AB  - Despite affecting millions of individuals, the etiology of hot flushes remains
      unknown. Here we review the physiology of hot flushes, CNS pathways regulating
      heat-dissipation effectors, and effects of estrogen on thermoregulation in animal
      models. Based on the marked changes in hypothalamic kisspeptin, neurokinin B and
      dynorphin (KNDy) neurons in postmenopausal women, we hypothesize that KNDy
      neurons play a role in the mechanism of flushes. In the rat, KNDy neurons project
      to preoptic thermoregulatory areas that express the neurokinin 3 receptor (NK3R),
      the primary receptor for NKB. Furthermore, activation of NK3R in the median
      preoptic nucleus, part of the heat-defense pathway, reduces body temperature.
      Finally, ablation of KNDy neurons reduces cutaneous vasodilatation and partially
      blocks the effects of estrogen on thermoregulation. These data suggest that
      arcuate KNDy neurons relay estrogen signals to preoptic structures regulating
      heat-dissipation effectors, supporting the hypothesis that KNDy neurons
      participate in the generation of flushes.

PMID- 23872334
TI  - Roles of sex and gonadal steroids in mammalian pheromonal communication.
AB  - A brain circuit (the accessory olfactory system) that originates in the
      vomeronasal organ (VNO) and includes the accessory olfactory bulb (AOB) plus
      additional forebrain regions mediates many of the effects of pheromones,
      typically comprised of a variety of non-volatile and volatile compounds, on
      aspects of social behavior. A second, parallel circuit (the main olfactory
      system) that originates in the main olfactory epithelium (MOE) and includes the
      main olfactory bulb (MOB) has also been shown to detect volatile pheromones from
      conspecifics. Studies are reviewed that point to specific roles of several
      different steroids and their water-soluble metabolites as putative pheromones.
      Other studies are reviewed that establish an adult, 'activational' role of
      circulating sex hormones along with sex differences in the detection and/or
      processing of non-steroidal pheromones by these two olfactory circuits.
      Persisting questions about the role of sex steroids in pheromonal processing are
      posed for future investigation. 

PMID- 23872335
TI  - One-dimensional hierarchical heterostructures of In2S3 nanosheets on electrospun
      TiO2 nanofibers with enhanced visible photocatalytic activity.
AB  - In2S3 nanosheets were assembled on electrospun TiO2 nanofibers template by a
      hydrothermal technique. For the obtained one-dimensional In2S3/TiO2 hierarchical
      heterostructures (1D In2S3/TiO2 H-HSs), the density and size of the secondary
      In2S3 nanosheets could be controlled by adjusting the reactant concentrations for
      the preparation of In2S3 in the hydrothermal process. The 1D In2S3/TiO2 H-HSs
      exhibited higher visible-light photocatalytic activity for the degradation of
      Methyl orange (MO) and the reduction of Cr(VI), as compared with the pure TiOv
      nanofibers and pure In2S3 nanosheets. The enhanced visible light photocatalytic
      activity might be attributed to the extended absorption in the visible light
      region from the narrow band-gap In2S3, the effective photogenerated electron-hole
      separation by the photosynergistic effects of the In2S3/TiO2 H-HSs and quick
      electron-transfer in the 1D TiO2 nanofibers. Meanwhile, the 1D In2S3/TiO2 H-HSs
      could be recycled easily by sedimentation due to their nanofibrous nonwoven web
      structure. Moreover, the mechanisms of photodegradation of MO and photoreduction
      of Cr(VI) were proposed through systematical investigations. This work provided
      new insights into utilizing 1D In2S3/TiO2 H-HSs as high efficiency visible-light
      driven photocatalysts for environmental remediation and energy conversion.

PMID- 23872336
TI  - Phytoremediation of perchlorate by free floating macrophytes.
AB  - Phytoremediation of perchlorate by free floating macrophytes (Eichornia, Pistia,
      Salvinia and Lemna) was evaluated in this study. Among the plants tested, Pistia
      showed 63.8 +/- 4% (w/v) removal of 5 mg/L level perchlorate in 7 days, whereas
      the removal was absent in other plants. Phyto-accumulation (18.2%) and rhizo
      degradation (45.68%) were identified as the mechanisms involved in perchlorate
      removal in Pistia. Whole plant extraction yielded 45.4 MUg perchlorate/g dry
      weight biomass in 7 days period. High intensity of light and presence of nitrate
      negatively affected perchlorate removal by Pistia. An enrichment of Pistia root
      homogenate exhibited faster reduction of perchlorate where 100mg/L of the
      compound was reduced completely in 48 h under anoxic condition. A novel
      perchlorate reducing bacterium, isolated from Pistia root homogenate enrichment
      was identified as Acinetobacter sp. NIIST (Genbank JX467695).

PMID- 23872337
TI  - Characterization of chemical agent transport in paints.
AB  - A combination of vacuum-based vapor emission measurements with a mass transport
      model was employed to determine the interaction of chemical warfare agents with
      various materials, including transport parameters of agents in paints. Accurate
      determination of mass transport parameters enables the simulation of the chemical
      agent distribution in a material for decontaminant performance modeling. The
      evaluation was performed with the chemical warfare agents bis(2-chloroethyl)
      sulfide (distilled mustard, known as the chemical warfare blister agent HD) and O
      ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), an
      organophosphate nerve agent, deposited on to two different types of polyurethane
      paint coatings. The results demonstrated alignment between the experimentally
      measured vapor emission flux and the predicted vapor flux. Mass transport
      modeling demonstrated rapid transport of VX into the coatings; VX penetrated
      through the aliphatic polyurethane-based coating (100 MUm) within approximately
      107 min. By comparison, while HD was more soluble in the coatings, the
      penetration depth in the coatings was approximately 2* lower than VX.
      Applications of mass transport parameters include the ability to predict agent
      uptake, and subsequent long-term vapor emission or contact transfer where the
      agent could present exposure risks. Additionally, these parameters and model
      enable the ability to perform decontamination modeling to predict how
      decontaminants remove agent from these materials.

PMID- 23872333
TI  - Sex differences and hormonal modulation of deep tissue pain.
AB  - Women disproportionately suffer from many deep tissue pain conditions.
      Experimental studies show that women have lower pain thresholds, higher pain
      ratings and less tolerance to a range of painful stimuli. Most clinical and
      epidemiological reports suggest female gonadal hormones modulate pain for some,
      but not all, conditions. Similarly, animal studies support greater nociceptive
      sensitivity in females in many deep tissue pain models. Gonadal hormones modulate
      responses in primary afferents, dorsal horn neurons and supraspinal sites, but
      the direction of modulation is variable. This review will examine sex differences
      in deep tissue pain in humans and animals focusing on the role of gonadal
      hormones (mainly estradiol) as an underlying component of the modulation of pain
      sensitivity. 

PMID- 23872338
TI  - Expression pattern of zinc-finger transcription factor Odd-skipped related 2 in
      murine development and neonatal stage.
AB  - The Odd-skipped gene, first identified as a Drosophila pair-rule zinc-finger
      transcription factor, plays an important role in Drosophila development. The
      mammalian homolog, Odd-skipped related 2 (Osr2), regulates limb, tooth, and
      kidney development in mouse embryos. However, the detailed expression pattern of
      Osr2 during neonatal development remains unclear. In this study, we investigated
      Osr2 expression patterns in mouse neonatal and embryo tissues using qPCR and in
      situ hybridization methods. First, we examined the tissue distribution of Osr2 by
      qPCR, and found it to be highly expressed in the uterus and moderately in the
      testes, small intestine, and prostate. That expression was also found in eye,
      kidney, placenta, lung, thymus, lymph node, stomach, and skeletal muscle tissues,
      and in all embryonic stages. On the other hand, Osr2 was not expressed in brain,
      heart, liver, or spleen samples. Next, we examined the tissue localization of
      Osr2 using in situ hybridization. Osr2 was found in the craniofacial region on
      E13.5, with notable expression in dental germ mesenchyme as well as the renal
      corpuscle on E17.5. As for neonatal tissues, Osr2 was expressed in the dental
      papilla, dental follicle, Harderian gland, nasal bone, eyelid dermis, synovial
      joint, and tibial subcutis. Our findings suggest that Osr2 functions in
      reproductive system organs, such as the uterus, testes, prostate, placenta, and
      ovaries. Furthermore, based on its expression in kidney, Harderian gland, eyelid
      dermis, and tibial subcutis tissues, this transcription factor may be involved in
      hormone synthesis and function. Together, our results demonstrate the role of
      Osr2 in postnatal development and embryogenesis. 

PMID- 23872339
TI  - Identification and expression analysis of BMP signaling inhibitors genes of the
      DAN family in amphioxus.
AB  - Bone morphogenetic proteins (BMPs) are members of the Transforming Growth Factor
      beta (TGF-beta) family implicated in many developmental processes in metazoans
      such as embryo axes specification. Their wide variety of actions is in part
      controlled by inhibitors that impede the interaction of BMPs with their specific
      receptors. Here, we focused our attention on the Differential screening-selected
      gene Aberrative in Neuroblastoma (DAN) family of inhibitors. Although they are
      well-characterized in vertebrates, few data are available for this family in
      other metazoan species. In order to understand the evolution of potential
      developmental roles of these inhibitors in chordates, we identified the members
      of this family in the cephalochordate amphioxus, and characterized their
      expression patterns during embryonic development. Our data suggest that the
      function of Cerberus/Dand5 subfamily genes is conserved among chordates, whereas
      Gremlin1/2 and NBL1 subfamily genes seem to have acquired divergent expression
      patterns in each chordate lineage. On the other hand, the expression of Gremlin
      in the amphioxus neural plate border during early neurulation strengthens the
      hypothesis of a conserved neural plate border gene network in chordates. 

PMID- 23872340
TI  - Expression of the decapentaplegic ortholog in embryos of the onychophoran
      Euperipatoides rowelli.
AB  - The gene decapentaplegic (dpp) and its homologs are essential for establishing
      the dorsoventral body axis in arthropods and vertebrates. However, the expression
      of dpp is not uniform among different arthropod groups. While this gene is
      expressed along the dorsal body region in insects, its expression occurs in a
      mesenchymal group of cells called cumulus in the early spider embryo. A cumulus
      like structure has also been reported from centipedes, suggesting that it might
      be either an ancestral feature of arthropods or a derived feature (=synapomorphy)
      uniting the chelicerates and myriapods. To decide between these two alternatives,
      we analysed the expression patterns of a dpp ortholog in a representative of one
      of the closest arthropod relatives, the onychophoran Euperipatoides rowelli. Our
      data revealed unique expression patterns in the early mesoderm anlagen of the
      antennal segment and in the dorsal and ventral extra-embryonic tissue, suggesting
      a divergent role of dpp in these tissues in Onychophora. In contrast, the
      expression of dpp in the dorsal limb portions resembles that in arthropods,
      except that it occurs in the mesoderm rather than in the ectoderm of the
      onychophoran limbs. A careful inspection of embryos of E. rowelli revealed no
      cumulus-like accumulation of dpp expressing cells at any developmental stage,
      suggesting that this feature is either a derived feature of chelicerates or a
      synapomorphy uniting the chelicerates and myriapods. 

PMID- 23872341
TI  - The microtubular cytoskeleton of the apusomonad Thecamonas, a sister lineage to
      the opisthokonts.
AB  - Apusomonads are of evolutionary interest because they are close relatives to the
      supergroup Opisthokonta, which contains both animals and fungi. There are no
      detailed morphological studies of 'amastigomonad' type apusomonads, such as
      Thecamonas trahens, despite this species having a sequenced genome. We use serial
      section transmission electron microscopy and 3D reconstruction to examine the
      cell architecture and complete microtubular cytoskeleton of Thecamonas.
      Thecamonas has two flagella and an anteriorly projecting 'tusk'. The anterior
      basal body associates with one microtubular root, which travels leftward, and a
      non-root 'ribbon' of six microtubules that travels down the right side of the
      cell. The posterior basal body associates with three roots: an eight-membered
      right root, a doublet left root, and an intermediate singlet root. These
      rearrange into two bands, both on the left side of the cell. One comprises the
      left and singlet roots plus one right root microtubule. The other comprises the
      remaining right root microtubules. A splitting right root and supernumerary
      singlet root are also present in breviates, ancyromonads, and 'typical
      excavates', suggesting that these characters are ancestral for much of eukaryote
      diversity. If so, opisthokonts, and most or all living eukaryotes, probably arose
      from cells with complex microtubular cytoskeletons. 

PMID- 23872342
TI  - Is executive function intact after pediatric intracranial hemorrhage? A sample of
      Mexican children with hemophilia.
AB  - The goal of this study was to examine executive functioning outcomes in children
      with hemophilia who have suffered intracranial hemorrhage. We assessed 10 boys
      with hemophilia with intracranial hemorrhage; 6 boys with hemophilia without
      intracranial hemorrhage; and 10 healthy boys as controls. Intellectual
      functioning was assessed with subscales from the Wechsler Intelligence Scale for
      Children-Mexican Revision. Concept formation and reasoning, cognitive
      flexibility, and planning and organization domains from a neuropsychological
      assessment battery for Spanish-speaking children were employed for our analysis.
      Results indicated that children with intracranial hemorrhage demonstrated
      significant impairment on some measures of executive function compared with the
      control groups. All differences reflected poorer performance by the intracranial
      hemorrhage group. These results may reflect the impact of disruption to immature
      brain circuits and the deficiency of functional specificity within the immature
      brain. This is the only known study examining neuropsychological functioning in
      Mexican youth with hemophilia. 

PMID- 23872343
TI  - Anticipated increases in medically attended injuries by children and young adults
      with the Affordable Care Act: the growing role of primary care in the pediatric
      trauma system.
AB  - OBJECTIVES: To guide implementation of the Affordable Care Act 2010 by estimating
      anticipated increases in medically attended injuries and site of care by the
      young who are currently uninsured. METHODS: The 2008 National Health Interview
      Survey was used to estimate injury episodes and care site for uninsured and
      insured youth <=26 years old. Increases in medically attended injuries were
      estimated by assuming that rates and care site for the currently uninsured would
      match those of the currently insured once the uninsured receive coverage.
      RESULTS: In 2008, approximately 11 938 800 episodes of medically attended
      injuries occurred for youth <=26 years. An anticipated 6.1% increase in medically
      attended injuries (737 081; 95% confidence interval = 564 000-879 000), the
      majority of which would be seen in the outpatient setting, could occur once all
      uninsured youth become insured. CONCLUSIONS: Injury prevention strategies and
      additional injury care training for primary care physicians may help ensure
      appropriate triage and optimal outcomes while containing costs.

PMID- 23872344
TI  - Recurrent fever in two children.

PMID- 23872345
TI  - Prevalence of vitamin D deficiency in international adoptees within the first 6
      months after adoption.
AB  - BACKGROUND: Vitamin D deficiency impairs bone health and development. OBJECTIVE:
      To determine the prevalence of and risk factors for vitamin D deficiency in
      pediatric international adoptees. METHODS: A prospective cohort (N = 189) study
      from a single international adoption clinic was conducted. Total 25-hydroxy
      vitamin D [25(OH)D] level was measured at the initial clinical assessment (within
      6 months of adoption). Vitamin D deficiency was defined as a 25(OH)D <20 ng/mL
      (<8 nmol/L) and insufficiency as 25(OH)D <30 ng/mL (<12 nmol/L). RESULTS: Vitamin
      D deficiency was diagnosed in 8% and insufficiency in 27% of the cohort. Lower
      body mass index and longer time in an institution were associated with vitamin D
      deficiency and insufficiency independent of age. CONCLUSIONS: Vitamin D
      insufficiency was common in our cohort of international adoptees. The
      significance of vitamin D insufficiency on bone development during the typical
      "catch-up" growth following international adoption needs to be determined.

PMID- 23872346
TI  - Improving safe sleep environments for well newborns in the hospital setting.
AB  - OBJECTIVE: Following the "Back to Sleep" campaign, deaths from sudden infant
      death syndrome (SIDS) were reduced. However, SIDS and sleep-related deaths
      continue to occur. Studies demonstrate that modeling by health care workers
      influences parents to place infants supine for sleep. Recently, additional
      emphasis has been placed on environment. The purpose of this study was to improve
      sleep position and environment in the hospital. METHODS: A Plan-Do-Study-Act
      cycle was initiated. Sleeping infants were observed at baseline. A bundled
      intervention was implemented; infants were again observed. Parents were surveyed.
      RESULTS: At baseline, 25% (36/144) of sleeping infants were safe; the majority of
      unsafe sleep was a result of environment. Postintervention, significantly more
      (58%; 145/249) had safe sleep (P < .0001). Most parents planned to use the supine
      position (95%; 96/101); none planned to cosleep. Many intended to adjust their
      infants' home sleep environment. CONCLUSION: Using a multifaceted approach
      significantly improved infant safe sleep practice in the hospital setting.

PMID- 23872347
TI  - Screening for syphilis in adolescents: how useful is it?

PMID- 23872348
TI  - Regional differences in myelination of chick vestibulocochlear ganglion cells.
AB  - In vertebrates, vestibular and cochlear ganglion (VG and CG, respectively) cells
      are bipolar neurons with myelinated axons and perikarya. The time course of the
      myelination of the VG and CG cells during development of chick embryos was
      investigated. Chick VG and CG from embryonic day at 7-20 (E7-20) were prepared
      for a transmission electron microscopy, myelin basic protein
      immunohistochemistry, and real-time quantitative RT-PCR. In the VG cells,
      myelination was first observed on the peripheral axons of the ampullar nerves at
      E10, on the utricular and saccular nerves at E12, and on the lagenar and neglecta
      nerves at E13. In the VG central axons, myelination was first seen on the
      ampullar nerves at E11, on the utricular and saccular nerves at E13, and on the
      lagenar nerves at E13. In the CG cells, the myelination was first observed on the
      peripheral and central axons at E14. In both VG and CG, myelination was observed
      on the perikarya at E17. These results suggest that the onset of the axonal
      myelination on the VG cells occurred earlier than that on the CG cells, whereas
      the perikaryal myelination occurred at about the same time on the both types of
      ganglion cells. Moreover, the myelination on the ampullar nerves occurred earlier
      than that on the utricular and saccular nerves. The myelination on the peripheral
      axons occurred earlier than that on the central axons of the VG cells, whereas
      that on the central and peripheral axons of the CG cells occurred at about the
      same time. The regional differences in myelination in relation to the onset of
      functional activities in the VG and CG cells are discussed. 

PMID- 23872349
TI  - A population-based case-control study of urinary arsenic species and squamous
      cell carcinoma in New Hampshire, USA.
AB  - BACKGROUND: Chronic high arsenic exposure is associated with squamous cell
      carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an
      important role in this association. However, little is known about the
      carcinogenicity of arsenic at levels commonly observed in the United States.
      OBJECTIVE: We estimated associations between total urinary arsenic and arsenic
      species and SCC in a U.S. population. METHODS: We conducted a population-based
      case-control SCC study (470 cases, 447 controls) in a U.S. region with moderate
      arsenic exposure through private well water and diet. We measured urinary iAs,
      monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these
      arsenic species (SigmaAs). Because seafood contains arsenolipids and arsenosugars
      that metabolize into DMA through alternate pathways, participants who reported
      seafood consumption within 2 days before urine collection were excluded from the
      analyses. RESULTS: In adjusted logistic regression analyses (323 cases, 319
      controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per
      liter increase in ln-transformed SigmaAs concentration [ln(SigmaAs)] (95% CI:
      1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC
      (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively).
      A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent
      iAs, MMA, and DMA were not associated with SCC. CONCLUSIONS: These results
      suggest that arsenic exposure at levels common in the United States relates to
      SCC and that arsenic metabolism ability does not modify the association.

PMID- 23872350
TI  - Downregulation of SnoN oncoprotein induced by antibiotics anisomycin and
      puromycin positively regulates transforming growth factor-beta signals.
AB  - BACKGROUND: SnoN and Ski proteins function as Smad transcriptional corepressors
      and are implicated in the regulation of diverse cellular processes such as
      proliferation, differentiation and transformation. Transforming growth factor
      beta (TGF-beta) signaling causes SnoN and Ski protein degradation via proteasome
      with the participation of phosphorylated R-Smad proteins. Intriguingly, the
      antibiotics anisomycin (ANS) and puromycin (PURO) are also able to downregulate
      Ski and SnoN proteins via proteasome. METHODS: We explored the effects of ANS and
      PURO on SnoN protein downregulation when the activity of TGF-beta signaling was
      inhibited by using different pharmacological and non-pharmacological approaches,
      either by using specific TbetaRI inhibitors, overexpressing the inhibitory Smad7
      protein, or knocking-down TbetaRI receptor or Smad2 by specific shRNAs. The
      outcome of SnoN and Ski downregulation induced by ANS or PURO on TGF-beta
      signaling was also studied. RESULTS: SnoN protein downregulation induced by ANS
      and PURO did not involve the induction of R-Smad phosphorylation but it was
      abrogated after TGF-beta signaling inhibition; this effect occurred in a cell
      type-specific manner and independently of protein synthesis inhibition or any
      other ribotoxic effect. Intriguingly, antibiotics seem to require components of
      the TGF-beta/Smad pathway to downregulate SnoN. In addition, SnoN protein
      downregulation induced by antibiotics favored gene transcription induced by TGF
      beta signaling. CONCLUSIONS: ANS and PURO require TGF-beta/Smad pathway to induce
      SnoN and Ski protein downregulation independently of inducing R-Smad2
      phosphorylation, which facilitates TGF-beta signaling. GENERAL SIGNIFICANCE:
      Antibiotic analogs lacking ribotoxic effects are useful as pharmacological tools
      to study TGF-beta signaling by controlling Ski and SnoN protein levels.

PMID- 23872351
TI  - Measuring chlorine bleach in biology and medicine.
AB  - BACKGROUND: Chlorine bleach, or hypochlorous acid, is the most reactive two
      electron oxidant produced in appreciable amounts in our bodies. Neutrophils are
      the main source of hypochlorous acid. These champions of the innate immune system
      use it to fight infection but also direct it against host tissue in inflammatory
      diseases. Neutrophils contain a rich supply of the enzyme myeloperoxidase. It
      uses hydrogen peroxide to convert chloride to hypochlorous acid. SCOPE OF REVIEW:
      We give a critical appraisal of the best methods to measure production of
      hypochlorous acid by purified peroxidases and isolated neutrophils. Robust ways
      of detecting it inside neutrophil phagosomes where bacteria are killed are also
      discussed. Special attention is focused on reaction-based fluorescent probes but
      their visual charm is tempered by stressing their current limitations. Finally,
      the strengths and weaknesses of biomarker assays that capture the footprints of
      chlorine in various pathologies are evaluated. MAJOR CONCLUSIONS: Detection of
      hypochlorous acid by purified peroxidases and isolated neutrophils is best
      achieved by measuring accumulation of taurine chloramine. Formation of
      hypochlorous acid inside neutrophil phagosomes can be tracked using mass
      spectrometric analysis of 3-chlorotyrosine and methionine sulfoxide in bacterial
      proteins, or detection of chlorinated fluorescein on ingestible particles.
      Reaction-based fluorescent probes can also be used to monitor hypochlorous acid
      during phagocytosis. Specific biomarkers of its formation during inflammation
      include 3-chlorotyrosine, chlorinated products of plasmalogens, and glutathione
      sulfonamide. GENERAL SIGNIFICANCE: These methods should bring new insights into
      how chlorine bleach is produced by peroxidases, reacts within phagosomes to kill
      bacteria, and contributes to inflammation. This article is part of a Special
      Issue entitled Current methods to study reactive oxygen species - pros and cons
      and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

PMID- 23872353
TI  - Epithelial cancer cells exhibit different electrical properties when cultured in
      2D and 3D environments.
AB  - BACKGROUND: Many drug development and toxicology studies are performed using
      cells grown in monolayers in well-plates and flasks, despite the fact that these
      are widely held to be different to cells found in the native environment. 3D,
      tissue engineered, organotypical tissue culture systems have been developed to be
      more representative of the native tissue environment than standard monolayer
      cultures. Whilst the biochemical differences between cells grown in 2D and 3D
      culture have been explored, the changes on the electrophysiological properties of
      the cells have not. METHODS: We compared the electrophysiological properties of
      primary normal oral keratinocytes (nOK) and cancerous abnormal oral keratinocytes
      (aOK), cultured in standard monolayer and reconstituted 3D organotypical tissue
      cultures. The electrophysiological properties of populations of the cells were
      analysed using dielectrophoresis. The intracellular conductivity of aOK was
      significantly increased when grown in organotypical cultures compared to
      counterpart cells grown in monolayer cultures. RESULTS: 3D cultured aOK showed
      almost identical intracellular conductivity to nOK also grown in organotypical
      cultures, but significantly different to aOK grown in monolayers. The effective
      membrane capacitance of aOK grown in 3D was found to be significantly higher than
      nOK, but there was no significant difference between the electrophysiological
      properties of nOK grown in 2D and 3D cultures. GENERAL SIGNIFICANCE: This work
      suggests that factors such as cell shape and cytoplasmic trafficking between
      cells play an important role in their electrophysiology, and highlights the need
      to use in vitro models more representative of native tissue when studying cell
      electrophysiological properties.

PMID- 23872354
TI  - Identification of potential protein dithiol-disulfide substrates of mammalian
      Grx2.
AB  - BACKGROUND: Glutaredoxins (Grxs) catalyze the reduction of protein disulfides via
      the dithiol mechanism and the de-/glutathionylation of substrates via the
      monothiol mechanism. These rapid, specific, and generally also reversible
      modifications are part of various signaling cascades regulating for instance cell
      proliferation, differentiation and apoptosis. Even though crucial functions of
      the conserved, mitochondrial Grx2a and the cytosolic/nuclear Grx2c isoforms have
      been proposed, only a few substrates have been identified in vitro or in vivo.
      The significance of redox signaling is emerging, yet a general lack of methods
      for the time-resolved analysis of these distinct and rapid modifications in vivo
      constitutes the biggest challenge in the redox signaling field. METHODS AND
      RESULTS: Here, we have identified potential interaction partners for Grx2
      isoforms in human HeLa cells and mouse tissues by an intermediate trapping
      approach. Some of the 50 potential substrates are part of the cytoskeleton or act
      in protein folding, cellular signaling and metabolism. Part of these interactions
      were further verified by immunoprecipitation or a newly established 2-D redox
      blot. CONCLUSIONS: Our study demonstrates that Grx2 catalyzes both the specific
      oxidation and the reduction of cysteinyl residues in the same compartment at the
      same time and without affecting the global cellular thiol-redox state. GENERAL
      SIGNIFICANCE: The knowledge of specific targets will be helpful in understanding
      the functions of Grx2. The 2-D redox blot may be useful for the analysis of the
      overall thiol-redox state of proteins with high molecular weight and numerous
      cysteinyl residues, that evaded analysis by previously described methods.

PMID- 23872355
TI  - Berberine combined with 2-deoxy-d-glucose synergistically enhances cancer cell
      proliferation inhibition via energy depletion and unfolded protein response
      disruption.
AB  - BACKGROUND: Targeting multiple aspects of cellular metabolism, such as both
      aerobic glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), has the
      potential to improve cancer therapeutics. Berberine (BBR), a widely used
      traditional Chinese medicine, exerts its antitumor effects by inhibiting OXPHOS.
      2-Deoxy-d-glucose (2-DG) targets aerobic glycolysis and demonstrates potential
      anticancer effects in the clinic. We hypothesized that BBR in combination with 2
      DG would be more efficient than either agent alone against cancer cell growth.
      METHODS: The effects of BBR and 2-DG on cancer cell growth were evaluated using
      the Sulforhodamine B (SRB) method. Cell death was detected with the PI uptake
      assay, and Western blot, Q-PCR and luciferase reporter assays were used for
      signaling pathway detection. An adenovirus system was used for gene
      overexpression. RESULTS: BBR combined with 2-DG synergistically enhanced the
      growth inhibition of cancer cells in vitro. Further mechanistic studies showed
      that the combination drastically enhanced ATP depletion and strongly disrupted
      the unfolded protein response (UPR). Overexpressing GRP78 partially prevented the
      cancer cell inhibition induced by both compounds. CONCLUSIONS: Here, we report
      for the first time that BBR and 2-DG have a synergistic effect on cancer cell
      growth inhibition related to ATP energy depletion and disruption of UPR. GENERAL
      SIGNIFICANCE: Our results propose the potential use of BBR and 2-DG in
      combination as an anticancer treatment, reinforcing the hypothesis that targeting
      both aerobic glycolysis and OXPHOS provides more effective cancer therapy and
      highlighting the important role of UPR in the process.

PMID- 23872352
TI  - Kinetic and mechanistic considerations to assess the biological fate of
      peroxynitrite.
AB  - BACKGROUND: Peroxynitrite, the product of the reaction between superoxide
      radicals and nitric oxide, is an elusive oxidant with a short half-life and a low
      steady-state concentration in biological systems; it promotes nitroxidative
      damage. SCOPE OF REVIEW: We will consider kinetic and mechanistic aspects that
      allow rationalizing the biological fate of peroxynitrite from data obtained by a
      combination of methods that include fast kinetic techniques, electron
      paramagnetic resonance and kinetic simulations. In addition, we provide a
      quantitative analysis of peroxynitrite production rates and conceivable steady
      state levels in living systems. MAJOR CONCLUSIONS: The preferential reactions of
      peroxynitrite in vivo include those with carbon dioxide, thiols and
      metalloproteins; its homolysis represents only <1% of its fate. To note, carbon
      dioxide accounts for a significant fraction of peroxynitrite consumption leading
      to the formation of strong one-electron oxidants, carbonate radicals and nitrogen
      dioxide. On the other hand, peroxynitrite is rapidly reduced by peroxiredoxins,
      which represent efficient thiol-based peroxynitrite detoxification systems.
      Glutathione, present at mM concentration in cells and frequently considered a
      direct scavenger of peroxynitrite, does not react sufficiently fast with it in
      vivo; glutathione mainly inhibits peroxynitrite-dependent processes by reactions
      with secondary radicals. The detection of protein 3-nitrotyrosine, a molecular
      footprint, can demonstrate peroxynitrite formation in vivo. Basal peroxynitrite
      formation rates in cells can be estimated in the order of 0.1 to 0.5MUMs(-1) and
      its steady-state concentration at ~1nM. GENERAL SIGNIFICANCE: The analysis
      provides a handle to predict the preferential fate and steady-state levels of
      peroxynitrite in living systems. This is useful to understand pathophysiological
      aspects and pharmacological prospects connected to peroxynitrite. This article is
      part of a Special Issue entitled Current methods to study reactive oxygen species
      - pros and cons and biophysics of membrane proteins. Guest Editor: Christine
      Winterbourn.

PMID- 23872356
TI  - A quality assurance initiative for commercial-scale production in high-throughput
      cryopreservation of blue catfish sperm.
AB  - Cryopreservation of fish sperm has been studied for decades at a laboratory
      (research) scale. However, high-throughput cryopreservation of fish sperm has
      recently been developed to enable industrial-scale production. This study treated
      blue catfish (Ictalurus furcatus) sperm high-throughput cryopreservation as a
      manufacturing production line and initiated quality assurance plan development.
      The main objectives were to identify: (1) the main production quality
      characteristics; (2) the process features for quality assurance; (3) the internal
      quality characteristics and their specification designs; (4) the quality control
      and process capability evaluation methods, and (5) the directions for further
      improvements and applications. The essential product quality characteristics were
      identified as fertility-related characteristics. Specification design which
      established the tolerance levels according to demand and process constraints was
      performed based on these quality characteristics. Meanwhile, to ensure integrity
      throughout the process, internal quality characteristics (characteristics at each
      quality control point within process) that could affect fertility-related quality
      characteristics were defined with specifications. Due to the process feature of
      100% inspection (quality inspection of every fish), a specific calculation
      method, use of cumulative sum (CUSUM) control charts, was applied to monitor each
      quality characteristic. An index of overall process evaluation, process capacity,
      was analyzed based on in-control process and the designed specifications, which
      further integrates the quality assurance plan. With the established quality
      assurance plan, the process could operate stably and quality of products would be
      reliable. 

PMID- 23872357
TI  - Sperm quality and the morphology of cryopreserved testicular tissues recovered
      post-mortem from diverse wild species.
AB  - This study compared the effects of slow and fast freezing of testicular tissue of
      wild animals collected at post-mortem on testicular structure and testicular
      sperm. The testes of seven animals that had died in captivity; three felids
      (jungle cat, lion and leopard), two cervids (rusa deer and fea's muntjac) and two
      bovids (Sumatran serows) were cryopreserved using slow- and fast-freezing
      protocols. There were greater reductions in the integrity of the sperm membrane
      and DNA in tissues cryopreserved using slow freezing compared to fast freezing
      (membrane integrity reduced by 21.5 +/- 12.4% vs. 13.0 +/- 6.9%, P = 0.11 and DNA
      integrity reduced by 22.7 +/- 16.3% vs. 6.6 +/- 6.3%, P = 0.13). Histologically,
      there were similar degrees of detachment and shrinkage of the seminiferous
      tubules whereas, TUNEL assay revealed a tendency towards more apoptotic changes
      in the intra-tubular cells of tissues frozen using fast freezing compared to slow
      freezing (P = 0.09). In conclusion, fast freezing tended to cause less damage to
      testicular sperm but its protective effect on intra-tubular cells was likely
      compromised. This is the first report of gamete recovery in the wild and of the
      comparison in various wildlife species, between testicular tissues cryopreserved
      using different protocols.

PMID- 23872358
TI  - Differential visceral nociceptive, behavioural and neurochemical responses to an
      immune challenge in the stress-sensitive Wistar Kyoto rat strain.
AB  - A highly regulated crosstalk exists between the immune and neuroendocrine systems
      with the altered immune responses in stress-related disorders being a valid
      example of this interaction. The Wister Kyoto (WKY) rat is an animal model with a
      genetic predisposition towards an exaggerated stress response and is used to
      study disorders such as depression and irritable bowel syndrome (IBS), where
      stress plays a substantial role. The impact of a lipopolysaccride (LPS) immune
      challenge has not yet been investigated in this animal model to date. Hence our
      aim was to assess if the stress susceptible genetic background of the WKY rat was
      associated with a differential response to an acute immune challenge. Central and
      peripheral parameters previously shown to be altered by LPS administration were
      assessed. Under baseline conditions, WKY rats displayed visceral hypersensitivity
      compared to Sprague Dawley (SD) control rats. However, only SD rats showed an
      increase in visceral sensitivity following endotoxin administration. The
      peripheral immune response to the LPS was similar in both strains whilst the
      central neurochemistry was blunted in the WKY rats. Sickness behaviour was also
      abrogated in the WKY rats. Taken together, these data indicate that the genetic
      background of the WKY rat mitigates the response to infection centrally, but not
      peripherally. This implies that heightened stress-susceptibility in vulnerable
      populations may compromise the coordinated CNS response to peripheral immune
      activation. 

PMID- 23872359
TI  - miRNA and mRNA expression profiling identifies members of the miR-200 family as
      potential regulators of epithelial-mesenchymal transition in pterygium.
AB  - The current study investigates whether microRNA (miRNA) regulators of epithelial
      mesenchymal transition (EMT), tissue fibrosis, and angiogenesis are
      differentially expressed in human primary pterygium. Genome-wide miRNA and mRNA
      expression profiling of paired pterygium and normal conjunctiva was performed in
      the context of conventional excision of pterygium with autotransplantation of
      conjunctiva (n = 8). Quantitative real time polymerase chain reaction (qRT-PCR)
      was used to validate the expression of key molecules previously detected by
      microarray. In pterygium, 25 miRNAs and 31 mRNAs were significantly
      differentially expressed by more than two-fold compared to normal conjunctiva. 14
      miRNAs were up-regulated (miR-1246, -486, -451, -3172, -3175, -1308, -1972, -143,
      -211, -665, -1973, -18a, 143, and -663b), whereas 11 were down-regulated (miR
      675, -200b-star, -200a-star, -29b, -200b, -210, -141, -31, -200a, -934, and 
      375). Unsupervised hierarchical cluster analysis demonstrated that members of the
      miR-200 family were coexpressed and down-regulated in pterygium. The molecular
      and cellular functions that were most significant to the miRNA data sets were
      cellular development, cellular growth and proliferation, and cellular movement.
      qRT-PCR confirmed the expression of 15 of the 16 genes tested and revealed that
      miR-429 was down-regulated by more than two-fold in pterygium. The concerted down
      regulation of four members from both clusters of the miR-200 family (miR-200a/
      200b/-429 and miR-200c/-141), which are known to regulate EMT, and up-regulation
      of the predicted target and mesenchymal marker fibronectin (FN1), suggest that
      EMT could potentially play a role in the pathogenesis of pterygium and might
      constitute promising new targets for therapeutic intervention in pterygium. 

PMID- 23872360
TI  - Plasma rich in growth factors (PRGF-Endoret) stimulates corneal wound healing and
      reduces haze formation after PRK surgery.
AB  - This study evaluated the efficacy of Plasma rich in growth factors (PRGF-Endoret)
      on the corneal wound healing process after Photorefractive keratectomy (PRK). To
      address this, blood from three healthy donors was collected, centrifuged and, the
      whole plasma column (WP) and the plasma fraction with the highest platelet
      concentration (F3) were collected. The effects of F3 and WP on the proliferation
      and migration of human corneal epithelial cells (HCE) were analyzed. PRK was
      performed on C57BL/6 mice. Animals were divided in three treatment groups:
      Control, F3, and WP. Corneal wound healing and haze formation were evaluated
      macroscopically. Eyes were collected at 1, 2, 3, and 7 days after surgery, and
      were processed for histological studies. Immunofluorescence was used to assess
      cellular proliferation, apoptosis and myofibroblast transformation in the mouse
      cornea. Results showed a significant increased on proliferation and wound healing
      after F3 and WP treatment when compared with control group. In vivo studies
      showed significant reduction on haze formation in mice treated with both PRGF
      Endoret formulations (F3 and WP). Histological studies showed an increase of
      epithelial cell proliferation in corneas of control group, promoting an
      epithelial hyperplasia. The number of SMA-positive cells (corresponding to
      myofibroblast differentiation) was significantly lower in the PRGF-Endoret group
      than in the control group, correlating with the higher transparence results
      observed macroscopically in both PRGF-Endoret groups. According to this, it can
      be concluded that PRGF-Endoret accelerates corneal tissue regeneration after PRK,
      reducing haze formation. 

PMID- 23872362
TI  - The efficient fabrication of corneal epithelial cell sheets by controlling oxygen
      concentration.
AB  - We have developed a novel method to accelerate the fabrication of epithelial cell
      sheets by controlling oxygen concentration. Rabbit limbal epithelial cells were
      proliferated efficiently under hypoxia (2% O2) in comparison to those
      proliferated under normoxia (20% O2), but were not stratified completely under 2%
      O2. In contrast, corneal limbal epithelial cells cultured under hypoxia were
      stratified by re-oxygenation after reaching confluence. Histological and
      immunofluorescence analyses and colony-forming assays showed that it was possible
      to fabricate the corneal epithelial cell sheets efficiently by controlling the
      oxygen concentration. These results indicate that this novel method can be a cost
      effective tool for fabricating stratified epithelial cell sheets for corneal
      regenerative medicine. 

PMID- 23872361
TI  - p62 expression and autophagy in alphaB-crystallin R120G mutant knock-in mouse
      model of hereditary cataract.
AB  - The formation of cataracts is associated with the accumulation of protein
      aggregates in the ocular lens, suggesting that defective protein degradation
      plays a role in cataract pathogenesis. Accumulation of the p62 protein has
      recently been identified as a marker for impaired autophagy in a variety of
      tissues; however, little information exists on its expression in the ocular lens
      and in cataracts. In the present study we examined the expression of p62 in the
      mouse lens and compared its expression in wild-type lenses with that in lenses
      from knock-in mice with an arginine to glycine mutation in alphaB-crystallin
      (alphaB-R120G) that is known to cause human hereditary cataract.
      Immunohistochemical, immunoblotting, and transmission electron microscopic
      analyses of wild type and alphaB-R120G mutant mice were performed. To assess the
      effect of increased protein aggregation on autophagy, immunohistochemical
      staining was performed with an anti-p62 antibody, revealing the presence of p62
      positive punctate staining in a band of denucleated cortical fiber cells. The
      number and size of p62 puncta were significantly greater in alphaB-R120G
      homozygous mutant lenses than in wild type and heterozygous mutant lenses. p62
      staining was also abundant in lens epithelial cells and was concentrated around
      the nuclear membrane. Double-membraned structures similar to autophagosomes
      containing cellular cytoplasmic content were detected in lens epithelial cells by
      transmission electron microscopy. The autophagosomes in lens epithelial cells
      from alphaB-R120G homozygous mutant mice were larger than those in wild type
      mice. Double-membraned structures that are probably autophagosomes were also
      detected in cortical fiber cells and were more abundant in the alphaB-R120G
      homozygous mutant lens than the wild type lens. This study demonstrates p62
      distribution as speckles in the lens fiber cells, altered levels of p62
      expression, and the presence of autophagosomes in the ocular lens of alphaB-R120G
      mutant mice. We propose that autophagy is inhibited in the alphaB-R120G mutant
      lenses because of a defect in protein degradation after autophagosome formation.
      Further work is necessary to determine the relationship between alphaB-crystallin
      function, autophagy, and cataract formation. 

PMID- 23872363
TI  - DNA alkylation damage and autophagy induction.
AB  - Many alkylating agents are used as chemotherapeutic drugs and have a long history
      of clinical application. These agents inflict a wide range of DNA damage
      resulting in a complex cellular response. After DNA damage, cells trigger a
      series of signaling cascades promoting cellular survival and cell cycle blockage
      which enables time for DNA repair to occur. More recently, induction of autophagy
      has been observed in cancer cells after treatment with different DNA-targeted
      anticancer drugs, including alkylating agents. Several studies have demonstrated
      that induction of autophagy after DNA damage delays apoptotic cell death and may
      therefore lead to chemoresistance, which is the limiting factor for successful
      chemotherapy. On the other hand, depending on the extent of damage and the
      cellular context, the induction of autophagy may also contribute to cell death.
      Given these conflicting results, many studies have been conducted to better
      define the role of autophagy in cancer cells in response to chemotherapy. In this
      review, we describe the main alkylating agents used in clinical oncology as well
      as the cellular response they evoke with emphasis on autophagy. 

PMID- 23872364
TI  - Effect of human 15-lipoxygenase-1 metabolites on vascular function in mouse
      mesenteric arteries and hearts.
AB  - Lipoxygenases regulate vascular function by metabolizing arachidonic acid (AA) to
      dilator eicosanoids. Previously, we showed that endothelium-targeted adenoviral
      vector-mediated gene transfer of the human 15-lipoxygenase-1 (h15-LO-1) enhances
      arterial relaxation through the production of vasodilatory
      hydroxyepoxyeicosatrienoic acid (HEETA) and trihydroxyeicosatrienoic acid (THETA)
      metabolites. To further define this function, a transgenic (Tg) mouse line that
      overexpresses h15-LO-1 was studied. Western blot, immunohistochemistry and RT-PCR
      results confirmed expression of 15-LO-1 transgene in tissues, especially high
      quantity in coronary arterial wall, of Tg mice. Reverse-phase HPLC analysis of
      [(14)C]-AA metabolites in heart tissues revealed enhanced 15-HETE synthesis in Tg
      vs. WT mice. Among the 15-LO-1 metabolites, 15-HETE, erythro-13-H-14,15-EETA, and
      11(R),12(S),15(S)-THETA relaxed the mouse mesenteric arteries to the greatest
      extent. The presence of h15-LO-1 increased acetylcholine- and AA-mediated
      relaxation in mesenteric arteries of Tg mice compared to WT mice. 15-LO-1 was
      most abundant in the heart; therefore, we used the Langendorff heart model to
      test the hypothesis that elevated 15-LO-1 levels would increase coronary flow
      following a short ischemia episode. Both peak flow and excess flow of reperfused
      hearts were significantly elevated in hearts from Tg compared to WT mice being
      2.03 and 3.22 times greater, respectively. These results indicate that h15-LO-1
      derived metabolites are highly vasoactive and may play a critical role in
      regulating coronary blood flow. 

PMID- 23872365
TI  - Communicating about quantity without a language model: number devices in homesign
      grammar.
AB  - All natural languages have formal devices for communicating about number, be they
      lexical (e.g., two, many) or grammatical (e.g., plural markings on nouns and/or
      verbs). Here we ask whether linguistic devices for number arise in communication
      systems that have not been handed down from generation to generation. We examined
      deaf individuals who had not been exposed to a usable model of conventional
      language (signed or spoken), but had nevertheless developed their own gestures,
      called homesigns, to communicate. Study 1 examined four adult homesigners and a
      hearing communication partner for each homesigner. The adult homesigners produced
      two main types of number gestures: gestures that enumerated sets (cardinal number
      marking), and gestures that signaled one vs. more than one (non-cardinal number
      marking). Both types of gestures resembled, in form and function, number signs in
      established sign languages and, as such, were fully integrated into each
      homesigner's gesture system and, in this sense, linguistic. The number gestures
      produced by the homesigners' hearing communication partners displayed some, but
      not all, of the homesigners' linguistic patterns. To better understand the
      origins of the patterns displayed by the adult homesigners, Study 2 examined a
      child homesigner and his hearing mother, and found that the child's number
      gestures displayed all of the properties found in the adult homesigners'
      gestures, but his mother's gestures did not. The findings suggest that number
      gestures and their linguistic use can appear relatively early in homesign
      development, and that hearing communication partners are not likely to be the
      source of homesigners' linguistic expressions of non-cardinal number. Linguistic
      devices for number thus appear to be so fundamental to language that they can
      arise in the absence of conventional linguistic input. 

PMID- 23872366
TI  - Multiple large foreign protein expression by a single recombinant baculovirus: a
      system for production of multivalent vaccines.
AB  - Baculovirus expression system offers the advantage of expression of several large
      proteins simultaneously by a single recombinant virus. To date, expression of
      multiple large (>100kDa) proteins has been hampered by the need to generate large
      constructs and repeat use of homologous sequence and promoter. The development of
      multi-loci baculovirus expression system overcomes these issues by enabling the
      recombination of large foreign sequences into different regions of the genome. In
      this paper, we have examined the co-expression of African horse sickness virus
      (AHSV) VP2 proteins from multiple serotypes in a single recombinant baculovirus.
      To this end, recombinant baculoviruses expressing multiple AHSV VP2 proteins were
      generated and it was found that up to six different AHSV serotypes (serotype 1,
      3, 4, 5, 7 and 8) VP2 proteins (~120kDa) could be expressed simultaneously from
      different loci of baculovirus genome. The expression of VP2 of one serotype was
      not significantly hindered by the presence of other serotypes, although there
      were slight differences in expression level between different serotypes. The
      expression of VP2 of further serotypes from additional loci resulted in a lesser
      expression level of VP2 proteins. Based on these findings, three additional
      recombinant baculoviruses encompassing all nine AHSV serotypes were constructed
      (serotypes 1, 7, 8 or serotypes 2, 4, 5 or serotypes 3, 6, 9) and each of the
      triple recombinant viruses exhibited similar expression level of each VP2. This
      system allows for the expression of a number of large proteins that has the
      potential to be exploited for multivalent vaccines production.

PMID- 23872367
TI  - Reply: Microcysts in the inner nuclear layer from optic atrophy are caused by
      retrograde trans-synaptic degeneration combined with vitreous traction on the
      retinal surface.

PMID- 23872368
TI  - Microcysts in the inner nuclear layer from optic atrophy are caused by retrograde
      trans-synaptic degeneration combined with vitreous traction on the retinal
      surface.

PMID- 23872369
TI  - Therapeutic potential of GABA(B) receptor ligands in drug addiction, anxiety,
      depression and other CNS disorders.
AB  - Glutamate and gamma-aminobutyric acid (GABA) are the major excitatory and
      inhibitory neurotransmitter systems, respectively in the central nervous system
      (CNS). Dysregulation, in any of these or both, has been implicated in various CNS
      disorders. GABA acts via ionotropic (GABA(A) and GABA(C) receptor) and
      metabotropic (GABA(B)) receptor. Dysregulation of GABAergic signaling and
      alteration in GABA(B) receptor expression has been implicated in various CNS
      disorders. Clinically, baclofen-a GABA(B) receptor agonist is available for the
      treatment of spasticity, dystonia etc., associated with various neurological
      disorders. Moreover, GABAB receptor ligands has also been suggested to be
      beneficial in various neuropsychiatric and neurodegenerative disorders. The
      present review is aimed to discuss the role of GABA(B) receptors and the possible
      outcomes of GABA(B) receptor modulation in CNS disorders.

PMID- 23872370
TI  - Oxytocinergic regulation of endogenous as well as drug-induced mood.
AB  - The interconnections between the serotonin and oxytocin pathways in the brain
      suggest that changes in oxytocin levels - arising from natural or drug-induced
      stimuli - lead to measureable changes in mood. In this paper, we review our
      findings in the context of what is known about the roles of oxytocin and
      vasopressin in the expression of a range of behaviours. In our first set of
      studies we investigated whether stimulation of oxytocin and vasopressin
      receptors, via central or systemic drug administration, would produce behavioural
      changes indicative of anti-depressant or anxiolytic activity. In our second study
      we investigated whether oxytocin receptor activation might be implicated in the
      interoceptive effects experienced with the popular party drug, MDMA ('ecstasy').
      Our first study demonstrated that carbetocin, an oxytocin analogue, had anti
      depressant actions following systemic and central administration, effects which
      were blocked by the oxytocin and vasopressin 1A receptor antagonist, atosiban.
      Carbetocin also had anxiolytic effects in the elevated plus maze. In an
      evaluation of the complementary nature of oxytocin and vasopressin, we found that
      systemic administration of desmopressin, a vasopressin analogue, was anxiogenic;
      its effects blocked by atosiban which on its own produced robust anxiolytic
      behavioural changes. In our second study, we evaluated MDMA's interoceptive
      effects using a drug discrimination paradigm. Carbetocin partially substituted
      for MDMA, while atosiban interfered with MDMA discrimination, suggesting that
      oxytocin receptor activation contributes to MDMA-related interoceptive cues. The
      results of these and other clinical and preclinical studies suggest that
      oxytocin, as well as its closely related counterpart vasopressin, may provide
      alternative therapeutic targets for the treatment of mood disorders such as
      anxiety and depression. The possibility that oxytocin release may contribute to
      the perception of and processes underlying natural and drug-induced behavioural
      reinforcement offers exciting prospects for future study. 

PMID- 23872372
TI  - Nicotinic receptor partial agonists modulate alcohol deprivation effect in
      C57BL/6J mice.
AB  - Relapse is a core feature of alcohol addiction and hinders the pharmacotherapy of
      alcohol use disorders. Pre-clinical and clinical studies have shown that neuronal
      nicotinic acetylcholine receptor (nAChR) partial agonists such as cytisine and
      its derivative, varenicline, reduce alcohol (ethanol) consumption and seeking
      behavior. However, the effects of these ligands on ethanol relapse are little
      understood. In the present study, we examined the effects of varenicline and
      cytisine on alcohol deprivation effect (ADE)--a validated model for relapse-like
      ethanol drinking in C57BL/6J mice. After habituation to 15% (v/v) ethanol intake
      using a continuous free-choice procedure, mice were exposed to alternating cycles
      of ethanol deprivation (5 days) and re-exposure (2 days). At the end of third
      deprivation cycle, animals received repeated intraperitoneal injections of
      saline, varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) and fluid
      intake was measured post 4 h and 24 h ethanol re-exposure. Repeated ethanol
      deprivation and re-exposure cycles significantly produced a robust and transient
      increase in ethanol (ADE). Pretreatment with varenicline (0.5 or 3.0 mg/kg) or
      cytisine (0.5 or 3.0 mg/kg) significantly reduced the expression of ADE at 4 h
      and 24 h after ethanol re-exposure. The results from this study indicate that
      nAChR partial agonists reduce the expression of ADE in mice and further suggest
      the involvement of nAChR mechanisms in ADE, a relapse-like ethanol drinking
      behavior.

PMID- 23872371
TI  - Conditioned reinforcement and locomotor activating effects of caffeine and
      ethanol combinations in mice.
AB  - A growing trend among ethanol drinkers, especially young adults, is to combine
      caffeinated energy drinks with ethanol during a drinking episode. The primary
      active ingredient of these mixers is caffeine, which may significantly interact
      with ethanol. We tested the two hypotheses that caffeine would enhance ethanol
      conditioned place preference and also enhance ethanol-stimulated locomotor
      activity. The interactive pharmacology of ethanol and caffeine was examined in
      C57BL/6J (B6) mice in a conditioned place preference procedure with 1.75 g/kg
      ethanol and 3 mg/kg caffeine. Additionally, we used B6 mice to evaluate
      ethanol/caffeine combinations on locomotor activity using 3 doses of ethanol
      (1.75, 2.5 and 3.25 g/kg) and 2 two doses of caffeine (3 and 15 mg/kg). Both
      ethanol and caffeine administered alone increased preference for the drug paired
      side, although the effect of caffeine was more modest than that of ethanol. The
      drug combination produced significant place preference itself, but this was not
      greater than that for ethanol alone. Additionally, the combination of caffeine
      and ethanol significantly increased locomotion compared to giving either drug
      alone. The effect was strongest with a stimulatory dose of ethanol (1.75 g/kg)
      and waned with increasing doses of ethanol. Thus, combinations of caffeine and
      ethanol had significant conditioned reinforcing and locomotor activating effects
      in mice.

PMID- 23872373
TI  - Effects of exogenous vasoactive intestinal peptide on mesenteric lymph pathway
      during early intestinal ischemia-reperfusion injury in rats.
AB  - Mesenteric lymph pathway serves as the primary route by which gut injury leads to
      systemic inflammation and distant organ injury. The inflammation of the
      intestinal tract is partially mediated by vasoactive intestinal peptide (VIP).
      Therefore, the aim of this study was to test whether exogenous VIP affects
      mesenteric lymph pathway during early intestinal ischemia-reperfusion (IIR)
      injury. Rats were randomized into control, control+VIP, IIR and IIR+VIP groups.
      The observation of mesenteric lymph flow was carried out by cannulation of
      mesenteric lymphatics. The distribution of in vivo lymphocyte trafficking was
      performed by (51)Cr labeled lymphocytes and was measured by gamma-counter.
      Endotoxin concentration was assayed using the limulus test kit and TNF-alpha
      level was detected by ELISA. When IIR injury treated with VIP, the volumes of
      lymph flow increased by 80%, which caused the number of lymphocytes exiting in
      mesenteric lymphatic increased by 50% while the proportion of (51)Cr-lymphocytes
      in Peyer's patches, intestinal effector tissues, mesenteric nodes, large
      intestine, stomach decreased by 58%, 51%, 58%, 63%, 64% respectively at the 6th h
      after reperfusion following intestinal ischemia. Meanwhile, endotoxin and TNF
      alpha levels in intestinal lymph decreased by 51% and 83%. These results suggest
      that exogenous VIP ameliorates IIR induced splanchnic organ damage via inhibition
      of toxic mediators reaching systemic circulation and reinforcement of the
      effective immune responses in gut-associated lymphoid tissues (GALT). 

PMID- 23872374
TI  - Functional characterization of acetylcholine receptors and calcium signaling in
      rat testicular capsule contraction.
AB  - The motor activity of mammalian testicular capsule (TC) contributes to male
      fertility and infertility, but the acetylcholine receptors related to the
      contractions induced by cholinergic drugs are poorly known. Indeed to
      characterize the acetylcholine receptors and cellular signaling by Ca(2+)
      involved in TC motor activity of rats, the potency of agonists (pD2) and
      antagonists (pA2) of acetylcholine receptors, and effects of Ca(2+) cellular
      transport blockers on the cholinergic contractions were evaluated. pD2 values of
      acetylcholine (5.98) were ten-fold higher than that of carbachol (4.99). Efficacy
      (Emax) of acetylcholine and carbachol to induce contractions corresponded to 95%
      and 97% of Emax for KCl, but Emax for nicotine was very low (8% of Emax for KCl).
      Further, physostigmine did not affect the acetylcholine potency. Contractions
      induced by acetylcholine or carbachol were antagonized by muscarinic but not
      nicotinic antagonist. The order of pA2 values obtained for muscarinic
      antagonists, namely atropine>4-DAMP>AF-DX116>pirenzepine, corresponded to a
      typical profile of M3 receptors. Contractions induced by acetylcholine or
      carbachol were inhibited by blockers of Ca(2+) influx through voltage-dependent
      calcium channels (nifedipine and Ni(2+)), Ca(2+) reuptake by sarco-endoplasmic
      reticulum (cyclopiazonic acid) and mitochondria (FCCP). The protein kinase C
      (PKC) inhibitor chelerythrine only affected the acetylcholine-induced
      contraction. These results suggest that TC motor activity of rats are mediated
      mainly by M3 receptors followed by the increase of cytosolic Ca(2+) concentration
      regulated by voltage-dependent calcium channels, sarco-endoplasmic reticulum and
      mitochondria. Furthermore, the differential effects of chelerythrine in the
      acetylcholine or carbachol-induced contractions are discussed.

PMID- 23872375
TI  - Curbing the focal adhesion kinase and its associated signaling events by
      pentoxifylline in MDA-MB-231 human breast cancer cells.
AB  - Pentoxifylline (PTX) is a methylxanthine derivative currently being used in the
      treatment of peripheral vascular diseases. Recently, we had evaluated its action
      in human MDA-MB-231 breast cancer cells. PTX exhibited anti-metastatic activity
      by affecting key processes such as proliferation, adhesion, migration, invasion
      and apoptosis. In light of the preliminary findings, the present work accounts
      for the possible mechanistic insights of the pathways affected by PTX. Aberrant
      Focal Adhesion Kinase (FAK) signaling forms a key determinant in breast cancer
      and in view of this fact we had investigated downstream processes regulated by
      FAK. PTX at sub-toxic doses lowers the level of activated FAK, Extracellular
      Regulated Kinase or Mitogen Activated Protein Kinase (ERK/MAPK), Protein Kinase B
      (PKB/Akt) affecting cellular proliferation and survival. It blocks G1/S phase of
      cell cycle by inhibiting the expression of Cyclin D1/Cdk6. Further, it modulates
      the activities of RhoGTPases and alters actin organization resulting in decreased
      motility. PTX also delays tumor growth and inhibited blood vessel formation in
      vivo. In purview of these findings, PTX surely qualifies as a suitable prospect
      in the intervention of breast cancer. 

PMID- 23872376
TI  - Comparison of the ex vivo receptor occupancy profile of ketamine to several NMDA
      receptor antagonists in mouse hippocampus.
AB  - NMDA receptor antagonists, particularly these targeting the GluN2B subunit are of
      therapeutic interest for the treatment of severe mood disorders. The receptor
      occupancy profiles of several NMDA receptor antagonists (30 mg/kg, s.c.) were
      compared in mouse hippocampus by ex vivo autoradiography using [(3)H]MK-801, a
      non-selective NMDA channel blocker, and [(3)H]ifenprodil a selective GluN2B
      antagonist. Subcutaneous administration of ketamine ((RS)-2-(2-Chlorophenyl)-2
      (methylamino)cyclohexanone) and memantine (3,5-dimethyladamantan-1-amine)
      inhibited [(3)H]MK-801 but not [(3)H]ifenprodil binding in mouse hippocampus.
      Ketamine reached maximal occupancy of [(3)H]MK-801 binding sites after 15 min and
      rapidly cleared from the brain with no significant level of occupancy measured at
      the 1h time point. Memantine significantly occupied [(3)H]MK-801 binding sites
      throughout the 6h time course. The selective GluN2B antagonist CP101,606 ((1S,2S)
      1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol) and Ro 25-6981
      ((alphaR,betaS)-alpha-(4-Hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1
      piperidinepropanol maleate) inhibited [(3)H]ifenprodil but not [(3)H]MK-801
      binding and significant levels of occupancy (above 50%) were measured throughout
      the 6h time course. These data highlight the unique quick pulse target engagement
      profile of ketamine compared to other NMDA receptor antagonists.

PMID- 23872377
TI  - Electrophysiological evidence for rapid 5-HT1A autoreceptor inhibition by
      vilazodone, a 5-HT1A receptor partial agonist and 5-HT reuptake inhibitor.
AB  - This study examined the effect of vilazodone, a combined serotonin (5-HT)
      reuptake inhibitor and 5-HT(1A) receptor partial agonist, paroxetine and
      fluoxetine on the sensitivity of 5-HT(1A) autoreceptors of serotonergic dorsal
      raphe nucleus neurons in rats. These effects were assessed by determining the
      intravenous dose of (+/-)-8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT)
      required to suppress the basal firing rate of these neurons by 50% (ID50) in
      anesthetized rats using in vivo electrophysiology. 5-HT uptake inhibition was
      determined by the ability of the compounds to reverse (+/-)-p-chloroamphetamine
      (PCA)-induced rat hypothalamic 5-HT depletion ex vivo. Acute vilazodone
      administration (0.63 and 2.1 umol/kg, s.c.), compared with vehicle, significantly
      increased (2-3-fold) the ID50 of 8-OH-DPAT at 4 h, but not 24h after
      administration. Subchronic administration (3 days) significantly increased the
      ID50 value at 4 h (3-4-fold) and at 24 h (~2-fold). In contrast, paroxetine and
      fluoxetine at doses that were supramaximal for 5-HT uptake inhibition did not
      significantly alter the ID50 value of 8-OH-DPAT after acute or subchronic
      administration. Vilazodone antagonized the action of PCA 3.5 h and 5 h after a
      single dose (ID50 1.49 and 0.46 umol/kg, s.c., respectively), but was inactive 18
      h post-administration, corroborating the electrophysiological results at 24 h
      following acute administration. The results are consistent with the concept of
      rapid and, following repeated treatment, prolonged inhibition of 5-HT(1A)
      autoreceptors by vilazodone. This effect could occur by either direct interaction
      with, or desensitization of, these receptors, an effect which cannot be ascribed
      to vilazodone's 5-HT reuptake inhibiting properties.

PMID- 23872378
TI  - Regulation of myometrial circulation and uterine vascular tone by constitutive
      nitric oxide.
AB  - Pregnancy is a physiological state that involves an increase in uterine blood
      flow, which is mediated in part by nitric oxide (NO) liberated from the
      endothelium and nitrergic neurons. The main focus of this review article is to
      provide information about how endogenous NO regulates uterine and placental blood
      flow and vascular tone in experimental animals and humans in vivo or in vitro in
      non-pregnant and pregnant states as well as pregnancy with pre-eclampsia. Uterine
      arteries from non-pregnant women respond to NO liberated from the endothelium and
      nitrergic nerves with relaxations, and the release of endothelial NO is
      influenced by the phase of the estrous cycle, with its enhanced release at the
      follicular phase when the estrogen level is high. NO bioavailability in the
      uteroplacental circulatory system is gradually increased during pregnancy. Pre
      eclamptic pregnancies with or without intrauterine growth restriction show
      impaired uteroplacental blood flow accompanied by reduced NO synthesis due to
      down-regulation of eNOS as well as asymmetric dimethylarginine accumulation and
      by augmented NO degradation by oxidative stress. Further studies are expected to
      provide new mechanistic insights into the fascinating process of maternal uterine
      adaptation in humans and novel prophylactic and therapeutic measures against pre
      eclampsia. 

PMID- 23872379
TI  - Metabonomic profiling in studying anti-osteoporosis effects of strontium fructose
      1,6-diphosphate on estrogen deficiency-induced osteoporosis in rats by GC/TOF-MS.
AB  - A novel strontium salt compound strontium fructose 1, 6-diphosphate (FDP-Sr) has
      been proved to have highly effective for bone loss via dual effects of
      stimulating bone formation and suppressing bone absorption. In the present study,
      metabolomic approach was used to identify and study potential biomarkers
      associated with the effect and safety of FDP-Sr. The metabolomic profiles of bone
      loss induced by estrogen deficiency in a rat model was described to attain a
      system-level map of the shift on the metabolic response in plasma using GC/TOF
      MS, after FDP-Sr was orally administered at the dose of 110 mg/kg/day for the
      prevention and 220 mg/kg/day for the treatment. Meanwhile, bone turnover
      biomarkers and bone mineral density were investigated to identify the specific
      changes of potential anti-osteoporosis effects of FDP-Sr. The differences in
      metabolic profiles between osteoporosis rats and FDP-Sr treated rats were well
      observed by the partial least squares-discriminant analysis (PLS-DA) to the MS
      spectra. Some metabolites including homocysteine, arachidonic acid, alanine, and
      hydroxyproline, which significantly changed during osteoporosis progression could
      be effectively reversed after FDP-Sr therapy. Of course some metabolites such as
      uric acid, glyceric acid, octadecadienoic acid, docosahexaenoic acid, oleic acid,
      and hexadecanoic acid were not found to reverse significantly after FDP-Sr
      administration. These results delineated the FDP-Sr effects-related metabolic
      alterations in the bone loss rats, suggesting that metabonomic analysis could
      provide helpful information on the new potential biomarkers relating to the
      mechanism of anti-osteoporosis action and side effects of FDP-Sr against estrogen
      deficiency induced bone loss.

PMID- 23872380
TI  - The use of carbetapentane for spinal anesthesia and use-dependent block of sodium
      currents.
AB  - Although carbetapentane produces skin (peripheral) infiltrative analgesia, the
      underlying mechanism of carbetapentane in local anesthesia is not well
      understood. The purpose of the study was to examine the effect of carbetapentane
      on voltage-gated Na(+) channels and its efficacy on spinal (central) anesthesia.
      We evaluated the effects of carbetapentane on rat motor and pain behavior (when
      administered intrathecally) and on voltage-gated sodium channels in
      differentiated neuronal NG108-15 cells. Carbetapentane exhibited dose-dependent
      spinal blockade with a more sensory-selective action over motor blockade
      (P<0.05). Carbetapentane was more potent than lidocaine (P<0.05) in spinal
      anesthesia. Intrathecal 5% dextrose (vehicle) elicited no spinal anesthesia.
      Lidocaine, used as a positive control, demonstrated concentration- and state
      dependent effects on tonic block of voltage-gated Na(+) currents (IC50 of 49.6
      and 194.6 uM at holding potentials of -70 and -100 mV, respectively).
      Carbetapentane was more potent (IC50 of 36.3 and 62.2 uM at holding potentials of
      -70 and -100 mV, respectively). Carbetapentane showed a much stronger frequency
      dependence of block than lidocaine: with high frequency stimulation (3.33 Hz), 50
      uM lidocaine produced an additional 30% blockade, while the same concentration of
      carbetapentane produced 70% more block. These results revealed carbetapentane had
      a more potent and prolonged spinal blockade with a more sensory/nociceptive
      selective action over motor blockade in comparison with lidocaine. Spinal
      anesthesia with carbetapentane could be through inhibition of voltage-gated Na(+)
      currents.

PMID- 23872381
TI  - Agmatine attenuates neuropathic pain in sciatic nerve ligated rats: modulation by
      hippocampal sigma receptors.
AB  - Present study investigated the influence of the sigma (sigma1 and sigma2)
      receptors within hippocampus on the agmatine induced antinociception in
      neuropathic rats. Animals were subjected to sciatic nerve ligation for induction
      of neuropathic pain and observed the paw withdrawal latency in response to
      thermal hyperalgesia, cold allodynia and the mechanical hyperalgesia.
      Intrahippocampal (i.h.) as well as intraperitoneal (i.p.) administration of
      agmatine attenuated neuropathic pain in sciatic nerve ligated rats.
      Intrahippocampal administration of sigma1 agonist (+)-pentazocine or sigma2
      agonist PB28 sensitized whereas, sigma1 antagonist BD1063 or sigma2 antagonist
      SM21 potentiated antinociceptive effect of agmatine. The behavioral effects
      correlated with hippocampal tumor necrosis factor-alpha (TNF-alpha) levels
      observed by western blot analysis. These results suggest that both the sigma1 and
      sigma2 receptor subunits within hippocampus play an important role in
      antinociceptive action of agmatine against neuropathic pain.

PMID- 23872382
TI  - PBOX-15 induces apoptosis and improves the efficacy of oxaliplatin in human
      colorectal cancer cell lines.
AB  - An emerging new class of targeted therapeutic molecules against the enzyme fatty
      acid amide hydrolase (FAAH) is a novel series of pyrrolo-1,5-benzoxa(thia)zepine
      compounds. A member of this family, pyrrolo-1,5-benzoxazepine-15 (PBOX-15), is a
      tubulin depolymerizing agent displaying a proapoptotic activity in a variety of
      human tumor cell types, including those derived from both solid and hematological
      malignancies, with minimal toxicity towards normal blood and bone marrow cells.
      In this study, we evaluated the PBOX-15-mediated effects in human colorectal
      cancer cell (CRC) lines. The compound, used at doses equal to or greater than 1
      MUM inhibits the proliferation of human CRC cell lines in a dose- and time
      dependent manner, inducing a significant cell cycle arrest in the G2/M phase. DNA
      fragmentation assays and western blot analysis demonstrated that treatments
      prolonged over 48 h triggered a strong activation of the intrinsic apoptotic
      pathway as indicated by activation of caspase-3, caspase-9 and PARP. Moreover,
      nanomolar doses of PBOX-15, unable to cause microtubule depolymerization,
      significantly improved the oxaliplatin and 5-fluouracil-induced anti
      proliferative effects in CRC cell lines. These results showed, for the first
      time, that PBOX-15 represents a promising compound for the treatment of human CRC
      and a strong candidate for novel therapeutic options.

PMID- 23872383
TI  - Sex differences in ischemia/reperfusion-induced acute kidney injury are dependent
      on the renal sympathetic nervous system.
AB  - Resistance to ischemic acute kidney injury has been shown to be higher in female
      rats than in male rats. We found that renal venous norepinephrine overflow after
      reperfusion played important roles in the development of ischemic acute kidney
      injury. In the present study, we investigated whether sex differences in the
      pathogenesis of ischemic acute kidney injury were derived from the renal
      sympathetic nervous system using male and female Sprague-Dawley rats.
      Ischemia/reperfusion-induced acute kidney injury was achieved by clamping the
      left renal artery and vein for 45 min followed by reperfusion, 2 weeks after
      contralateral nephrectomy. Renal function was impaired after reperfusion in both
      male and female rats; however, renal dysfunction and histological damage were
      more severe in male rats than in female rats. Renal venous plasma norepinephrine
      levels after reperfusion were markedly elevated in male rats, but were not in
      female rats. These sex differences were eliminated by ovariectomy or treatment
      with tamoxifen, an estrogen receptor antagonist, in female rats. Furthermore, an
      intravenous injection of hexamethonium (25mg/kg), a ganglionic blocker, 5 min
      before ischemia suppressed the elevation in renal venous plasma norepinephrine
      levels after reperfusion, and attenuated renal dysfunction and histological
      damage in male rats, and ovariectomized and tamoxifen-treated female rats, but
      not in intact females. Thus, the present findings confirmed sex differences in
      the pathogenesis of ischemic acute kidney injury, and showed that the attenuation
      of ischemia/reperfusion-induced acute kidney injury observed in intact female
      rats may be dependent on depressing the renal sympathetic nervous system with
      endogenous estrogen.

PMID- 23872384
TI  - Spinal and peripheral adenosine A1 receptors contribute to antinociception by
      tramadol in the formalin test in mice.
AB  - Tramadol, an analgesic used alone or combined with acetaminophen, has a complex
      mechanism of action involving opioid and amine mechanisms. In this study, we
      explored the involvement of spinal and peripheral adenosine A1 receptors in
      antinociception by tramadol, and determined whether spinal serotonin 5-HT7
      receptors were linked to spinal A1 receptor actions. Antinociception was examined
      using the 2% formalin test in mice. Tramadol was administered systemically
      (intraperitoneal) or peripherally (intraplantar). Caffeine (non-selective A1/A2A
      receptor antagonist) and SCH58261 (selective A2A receptor antagonist) were given
      systemically, while DPCPX (selective A1 receptor antagonist) was given
      systemically, spinally (lumbar puncture), or peripherally. Systemic tramadol 35
      mg/kg produced antinociception against phase 2 formalin-evoked flinching
      behaviors, particularly in the earlier parts (phase 2A). Systemic caffeine (10
      mg/kg) and DPCPX (1 mg/kg), but not SCH58261 (3 mg/kg), inhibited antinociception
      by systemic tramadol. Spinal DPCPX 3 MUg also inhibited the action of systemic
      tramadol. Spinal SB269970 (selective 5-HT7 receptor antagonist) 3-10 MUg did not
      alter the effect of systemic tramadol. Intraplantar tramadol produced
      antinociception against flinching behaviors, and this action was reversed by
      intraplantar DPCPX 4.5 MUg administered on the ipsilateral, but not
      contralateral, side. Intraplantar DPCPX also reversed antinociception by systemic
      tramadol. These results indicate that adenosine A1 receptors contribute to
      antinociception by tramadol in the mouse formalin model, and that spinal and
      peripheral sites are involved in these actions. 5HT7 receptors in the spinal cord
      do not appear to be involved in the recruitment of A1 receptor mechanisms when
      tramadol is given systemically in this model.

PMID- 23872385
TI  - Community-based participatory research in complex settings: clean mind-dirty
      hands.
AB  - Despite the abundance of the literature which discusses factors supporting or
      inhibiting effective participation of community members in community-based
      research, there is a paucity of publications analysing challenges to
      participation in complex settings. This manuscript describes an intervention
      built on researcher-community partnership amid complex social conditions which
      challenged participation of community members at different stages of the research
      process. The research took place in a Palestinian refugee camp in Beirut, Lebanon
      and 1 of 12 in Lebanon which suffer from deteriorating social, economic and
      physical conditions perpetuated by state-imposed restrictions. The research team
      developed a community coalition which was involved in all stages of planning,
      designing, implementation and dissemination. In all those stages the aim was to
      maintain rigorous research, to follow a 'clean mind' approach to research, but
      maintain principles of community participation which necessitate 'a dirty hand'.
      Despite commitment to the principles of community-based participatory research,
      participation of community members (including youth, parents and teachers) was
      affected to a great extent by the social, physical and structural conditions of
      the community context. Characteristics of the context where research is conducted
      and how it affects community members should not be overlooked since multiple
      factors beyond the researchers' control could interfere with the rigour of
      scientific research. Researchers need to develop a plan for participation with
      the community from the beginning with an understanding of the community forces
      that affect meaningful participation and address possible deterrence. 

PMID- 23872386
TI  - Organizational capacities for health promotion implementation: results from an
      international hospital study.
AB  - In this article, organizational structures in hospitals are discussed as possible
      capacities for hospital health promotion (HP) implementation, based on data from
      the PRICES-HPH study. PRICES-HPH is a cross-sectional evaluation study of the
      International Network of Health Promoting Hospitals & Health Services (HPH
      Network) and was conducted in 2008-2012. Data from 159 acute care hospitals were
      used in the analysis. Twelve organizational structures, which were denoted as
      possible organizational health promotion capacities in previous literature, were
      tested for their association with certain strategic HP implementation approaches.
      Four organizational structures were significantly (p = 0.05) associated with one
      or more elaborate and comprehensive strategic HP implementation approaches: (1) a
      health promotion specific quality assessment routine; (2) an official hospital
      health promotion team; (3) a fulltime hospital health promotion coordinator; and
      (4) officially documented health promotion policies, strategies or standards. The
      results add further evidence to the importance of organizational capacity
      structures for hospital health promotion and identify four tangible structures as
      likely candidates for organizational HP capacities in hospitals.

PMID- 23872387
TI  - Associations between plasma persistent organic pollutant levels and blood
      pressure in Inuit adults from Nunavik.
AB  - BACKGROUND: Recent evidence suggests that exposure to persistent organic
      pollutants (POPs) increases the risk of hypertension in environmentally exposed
      populations. High POP levels have been detected in Arctic populations and the
      exposure is related to high consumption of fish and marine mammals, which
      represent the traditional diet of these populations. OBJECTIVE: We examined the
      associations between polychlorinated biphenyls (PCBs), organochlorine (OC)
      pesticides and hypertension among Inuit from Nunavik (Quebec, Canada). METHODS: A
      complete set of data was obtained for 315 Inuit>=18years who participated in the
      "Sante Quebec" health survey that was conducted in the 14 villages of Nunavik in
      1992. Fourteen polychlorinated biphenyls (PCBs) and 8 OC pesticides or their
      metabolites were measured in plasma samples using gas chromatography with
      electron capture detection. Blood pressure (BP) was measured using a standardized
      protocol and information regarding anti-hypertensive medication was obtained
      through questionnaires. The associations between log-transformed POPs and
      hypertension (systolic BP>=140mmHg, diastolic BP>=90mmHg or anti-hypertensive
      medication) were analyzed using multiple logistic regressions. RESULTS: Total
      PCBs as well as the sum of non-dioxin-like PCBs were significantly associated
      with higher risk of hypertension. Furthermore, the risk of hypertension increased
      with higher plasma concentrations of congeners 101, 105, 138 and 187. Models
      adjusted for BP risk factors became significant after including n-3
      polyunsaturated fatty acids (PUFAs) and further adjustment for lead and mercury
      did not change the results. Regarding OC pesticides, p,p'
      dichlorodiphenyldichloroethylene (p,p'-DDE) was associated with increased risk of
      hypertension while inverse associations were observed with p,p'
      dichlorodiphenyltrichloroethane (p,p'-DDT), beta-hexachlorocyclohexane (HCH) and
      oxychlordane. CONCLUSIONS: Some PCB congeners were associated with higher risk of
      hypertension in this highly exposed population. Most associations became
      significant after including n-3 PUFAs in the models. However, the analyses of OC
      pesticides revealed divergent results, which need to be confirmed in further
      cohort and experimental studies.

PMID- 23872388
TI  - Baseline levels and trophic transfer of persistent organic pollutants in
      sediments and biota from the Congo River Basin (DR Congo).
AB  - The present study aimed to evaluate the occurrence of persistent organic
      pollutants (POPs: (PCBs, PBDEs, DDTs, HCHs, CHLs and HCB) in sediments and biota
      from the middle Congo River Basin (CRB) and to investigate their trophic transfer
      through the aquatic food web using nitrogen stable isotope ratios. To our
      knowledge, no data on levels of POPs in sediment and biota from the CRB are
      present in the literature, and studies on trophic transfer and biomagnification
      profiles of POPs using delta(15)N are scarce in tropical regions. POP levels in
      the sediment and biota were low, with exception of total PCB levels found in fish
      from the Itimbiri River (1.4 to 44ng/g ww). Compared to concentrations found in
      fish from pristine to relatively industrial developed areas, the ?PCB levels in
      fish from the Itimbiri were high, indicating the presence of a local PCB
      contamination source in this catchment. Based on minimum risk level criteria
      formulated by ATSDR, the consumption of PCB contaminated fish from the Itimbiri
      river poses a potential risk for humans. The POP levels in biota were not
      significantly related to the POP levels in sediments, and the BSAF concept (Biota
      Sediment Accumulation Factor) was found to be a poor predictor of the
      bioavailability and bioaccumulation of environmental pollutants in the present
      study. With increasing trophic levels, a significant increase in PCB 95, 101,
      110, 138, 146, 149, 153, 174, 180 & 187 and p,p'-DDT in Itimbiri and BDE 47 & 99
      in Itimbiri, Aruwimi & Lomami river basins was observed. Trophic magnification
      factors were higher than 1, indicating that biomagnification occurs through the
      tropical food web. 

PMID- 23872389
TI  - Attenuating Abeta1-42-induced toxicity by a novel acetylcholinesterase inhibitor.
AB  - We explored the attenuating effects of NP-9 on beta-amyloid (Abeta) aggregation
      and amyloid-induced toxicity. NP-9 is a recently reported monoamine oxidase B
      (MAO-B), and acetylcholinesterase (AChE) inhibitor. In the present study, we
      found that NP-9 inhibited AChE activity in a dose-dependent manner with a maximal
      inhibition dose of 8 mg/kg, i.p. It inhibited Abeta aggregation, observed through
      thioflavin-T assay (IC50=60 MUM) and scanning electron microscopy (S.E.M.) (no
      fibril formation). NP-9 has shown marked protection against scopolamine and
      Abeta1-42-induced memory impairments. It also minimized neuronal loss and amyloid
      plaque deposition in the brains of Abeta1-42-induced mice model. Therefore, NP-9
      could be a promising lead molecule for AD, with effects against MAO-B, AChE,
      Abeta aggregation, and Abeta1-42 induced toxicity.

PMID- 23872391
TI  - Early gamma oscillations.
AB  - Gamma oscillations have long been considered to emerge late in development.
      However, recent studies have revealed that gamma oscillations are transiently
      expressed in the rat barrel cortex during the first postnatal week, a "critical"
      period of sensory-dependent barrel map formation. The mechanisms underlying the
      generation and physiological roles of early gamma oscillations (EGOs) in the
      development of thalamocortical circuits will be discussed in this review. In
      contrast to adult gamma oscillations, synchronized through gamma-rhythmic
      perisomatic inhibition, EGOs are primarily driven through feedforward gamma
      rhythmic excitatory input from the thalamus. The recruitment of cortical
      interneurons to EGOs and the emergence of feedforward inhibition are observed by
      the end of the first postnatal week. EGOs facilitate the precise synchronization
      of topographically aligned thalamic and cortical neurons. The multiple replay of
      sensory input during EGOs supports long-term potentiation at thalamocortical
      synapses. We suggest that this early form of gamma oscillations, which is
      mechanistically different from adult gamma oscillations, guides barrel map
      formation during the critical developmental period. 

PMID- 23872390
TI  - Minimal NF-kappaB activity in neurons.
AB  - Nuclear factor-kappa B (NF-kappaB) is a ubiquitous transcription factor that
      regulates immune and cell-survival signaling pathways. NF-kappaB has been
      reported to be present in neurons wherein it reportedly responds to immune and
      toxic stimuli, glutamate, and synaptic activity. However, because the brain
      contains many cell types, assays specifically measuring neuronal NF-kappaB
      activity are difficult to perform and interpret. To address this, we compared NF
      kappaB activity in cultures of primary neocortical neurons, mixed brain cells,
      and liver cells, employing Western blot of NF-kappaB subunits, electrophoretic
      mobility shift assay (EMSA) of nuclear kappaB DNA binding, reporter assay of
      kappaB DNA binding, immunofluorescence of the NF-kappaB subunit protein p65,
      quantitative real-time polymerase chain reaction (PCR) of NF-kappaB-regulated
      gene expression, and enzyme-linked immunosorbent assay (ELISA) of produced
      proteins. Assay of p65 showed its constitutive presence in cytoplasm and nucleus
      of neurons at levels significantly lower than in mixed brain or liver cells. EMSA
      and reporter assays showed that constitutive NF-kappaB activity was nearly absent
      in neurons. Induced activity was minimal--many fold lower than in other cell
      types, as measured by phosphorylation and degradation of the inhibitor
      IkappaBalpha, nuclear accumulation of p65, binding to kappaB DNA consensus sites,
      NF-kappaB reporting, or induction of NF-kappaB-responsive genes. The most
      efficacious activating stimuli for neurons were the pro-inflammatory cytokines
      tumor necrosis factor alpha (TNFalpha) and interleukin-beta (IL-beta). Neuronal
      NF-kappaB was not responsive to glutamate in most assays, and it was also
      unresponsive to hydrogen peroxide, lipopolysaccharide, norepinephrine, ATP,
      phorbol ester, and nerve growth factor. The chemokine gene transcripts CCL2,
      CXCL1, and CXCL10 were strongly induced via NF-kappaB activation by TNFalpha in
      neurons, but many candidate responsive genes were not, including the
      neuroprotective genes SOD2 and Bcl-xL. Importantly, the level of induced neuronal
      NF-kappaB activity in response to TNFalpha or any other stimulus was lower than
      the level of constitutive activity in non-neuronal cells, calling into question
      the functional significance of neuronal NF-kappaB activity.

PMID- 23872392
TI  - Oral administration of glutathione improves memory deficits following transient
      brain ischemia by reducing brain oxidative stress.
AB  - Oxidative stress aggravates brain injury following ischemia. The glutathione
      (GSH) system plays a pivotal role in combating oxidative stress in various cell
      types. To determine whether oral GSH administration elicits anti-oxidative
      effects, we assessed its potential neuroprotective effects in transient bilateral
      common carotid artery occlusion (BCCAO) mice. In naive mice, acute oral
      administration of GSH significantly increased GSH levels by 1h in the cortex and
      hippocampus. Eleven days after BCCAO, untreated mice showed significantly
      decreased GSH levels and an inverse elevation of glutathione-disulfide (GSSG)
      levels in both the cortex and hippocampus. Oral administration of GSH (100 and
      500 mg/kg p.o.) for 10 consecutive days after ischemia restored reduced GSH
      levels and inhibited GSSG elevation. Notably, post-administration of GSH (100 and
      500 mg/kg p.o.) significantly prevented neuronal cell death in the hippocampal
      CA1 region in BCCAO mice, an effect closely correlated with decreased levels of
      oxidative markers such as 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2-deoxyguanosine
      (8-OHdG) and nitrotyrosine in that region. Finally, GSH administration for 10
      days improved memory deficits observed in BCCAO mice. Taken together, our
      findings indicate that the anti-oxidative effect of oral GSH administration
      ameliorates post-ischemia neuronal cell death and, in turn, may improve memory.

PMID- 23872393
TI  - Neuroprotective efficacy of subcutaneous insulin-like growth factor-I
      administration in normotensive and hypertensive rats with an ischemic stroke.
AB  - The aim of this study was to test the insulin-like growth factor-I (IGF-I) as a
      neuroprotective agent in a rat model for ischemic stroke and to compare its
      neuroprotective effects in conscious normotensive and spontaneously hypertensive
      rats. The effects of subcutaneous IGF-I injection were investigated in both rat
      strains using the endothelin-1 rat model for ischemic stroke. Motor-sensory
      functions were measured using the Neurological Deficit Score. Infarct size was
      assessed by Cresyl Violet staining. Subcutaneous administration of IGF-I resulted
      in significantly reduced infarct volumes and an increase in motor-sensory
      functions in normotensive rats. In these rats, IGF-I did not modulate blood flow
      in the striatum and had no effect on the activation of astrocytes as assessed by
      GFAP staining. In hypertensive rats, the protective effects of IGF-I were smaller
      and not always significant. Furthermore, IGF-I significantly reduced microglial
      activation in the cortex of hypertensive rats, but not in normotensive rats. More
      detailed studies are required to find out whether the reduction by IGF-I of
      microglial activation contributes to an impairment IGF-I treatment efficacy.
      Indeed, we have shown before that microglia in hypertensive rats have different
      properties compared to those in control rats, as they exhibit a reduced
      responsiveness to ischemic stroke and lipopolysaccharide. 

PMID- 23872394
TI  - Effects of withdrawal from repeated amphetamine exposure in peri-puberty on
      neuroplasticity-related genes in mice.
AB  - Although extensive evidence demonstrates that repeated administration of
      amphetamine (AMPH) induces behavioral and neurochemical sensitization, the
      influence of the developmental timing of AMPH administration is unknown. This is
      an important issue to address because it could help clarify the influence of
      early drug exposure on neuronal plasticity and the involvement of dopaminergic
      sensitization in the etiopathology of neuropsychiatric disorders. Thus, we
      decided to investigate the molecular alterations induced by the administration of
      AMPH during adolescence, when repeated exposure to the psychostimulant may
      interfere with developmental neuroplasticity. We investigated the expression of
      the neurotrophin brain-derived neurotrophic factor (BDNF) and of two inducible
      early genes (arc and cfos) that bridge neuronal activity with long-lasting
      functional alterations. We found that peri-pubertal treatment with AMPH induces
      long-lasting changes in the expression of bdnf and of activity-regulated genes in
      the hippocampus and in the prefrontal/frontal cortex, and leads to alterations of
      their short-term modulation in response to a subsequent acute AMPH challenge.
      These data suggest that AMPH exposure in peri-puberty may negatively affect the
      maturation of brain structures, such as the prefrontal cortex, which facilitate
      the development of dopamine sensitization and may contribute to dopamine
      dependent behavioral dysfunctions and molecular alterations in adulthood. 

PMID- 23872395
TI  - Ageing of trees: application of general ageing theories.
AB  - The main questions posed in ageing theories are how ageing evolved and whether or
      not it is programmed. While these questions have not yet been clearly resolved,
      several groups of possible theories have been published on this topic. However,
      most of these theories do not consider plants, and the specific traits involved
      in their ageing mechanisms. The first trait covers clonality and sectoriality and
      the second concerns the lack of a differentiated germ line. The lack of a germ
      line prevents telomere shortening which can lead to the transfer of somatic
      mutations into sexual offspring, while sectoriality in trees causes isolation of
      potentially catastrophic events in one tree part, thus creating a population of
      more or less independent modules within one axis. The processes of population
      dynamics, including ageing, can act within the framework of an individual tree as
      well as in that of the population as a whole, although the processes involved
      differ and consequently result in different effects.

PMID- 23872396
TI  - Interference of selenium and selenoproteins with the insulin-regulated
      carbohydrate and lipid metabolism.
AB  - An assumed link between supranutritional intake of the micronutrient selenium
      (Se) and type 2 diabetes mellitus is discussed controversially. Se concentrations
      in the habitual diet and in dietary supplements are probably not sufficient to
      induce overt diabetes in healthy individuals. On the other hand, high plasma Se
      and selenoprotein P (Sepp1) levels have been found to be associated with
      biomarkers of an impaired carbohydrate and lipid homeostasis in humans. Moreover,
      abundant expression of antioxidant selenoproteins due to dietary Se oversupply
      resulted in hyperinsulinemia and decreased insulin sensitivity in animal models.
      This review discusses findings from animal and cell culture studies in search of
      molecular mechanisms underlying an interference of Se and selenproteins such as
      the Se transport and supply protein Sepp1 and the hydrogen peroxide-reducing
      selenoenzyme glutathione peroxidase 1 (GPx1) with insulin-controlled metabolic
      pathways. A probable rationale derives from the positive and negative regulation
      of both glucose-induced insulin secretion and insulin-induced signaling by
      hydrogen peroxide. Se status and GPx1 expression have been reported to affect the
      activity of insulin-antagonistic phosphatases that are regulated by hydrogen
      peroxide-mediated reversible oxidation of catalytic cysteine residues. GPx1
      and/or Sepp1 inhibited phosphorylation (activation) of key mediators in energy
      metabolism such as protein kinase B (Akt) and AMP-activated protein kinase (AMPK)
      in liver and/or skeletal muscle. Conversely, a dys-regulated carbohydrate
      metabolism in diabetes might affect plasma Se and Sepp1 levels, as the hepatic
      biosynthesis of Sepp1 is suppressed by insulin and stimulated under hyperglycemic
      conditions. 

PMID- 23872397
TI  - Deconvoluting the role of reactive oxygen species and autophagy in human
      diseases.
AB  - Reactive oxygen species (ROS), chemically reactive molecules containing oxygen,
      can form as a natural byproduct of the normal metabolism of oxygen and also have
      their crucial roles in cell homeostasis. Of note, the major intracellular sources
      including mitochondria, endoplasmic reticulum (ER), peroxisomes and the NADPH
      oxidase (NOX) complex have been identified in cell membranes to produce ROS.
      Interestingly, autophagy, an evolutionarily conserved lysosomal degradation
      process in which a cell degrades long-lived proteins and damaged organelles, has
      recently been well-characterized to be regulated by different types of ROS.
      Accumulating evidence has demonstrated that ROS-modulated autophagy has numerous
      links to a number of pathological processes, including cancer, ageing,
      neurodegenerative diseases, type-II diabetes, cardiovascular diseases, muscular
      disorders, hepatic encephalopathy and immunity diseases. In this review, we focus
      on summarizing the molecular mechanisms of ROS-regulated autophagy and their
      relevance to diverse diseases, which would shed new light on more ROS modulators
      as potential therapeutic drugs for fighting human diseases. 

PMID- 23872398
TI  - Health and household air pollution from solid fuel use: the need for improved
      exposure assessment.
AB  - BACKGROUND: Nearly 3 billion people worldwide rely on solid fuel combustion to
      meet basic household energy needs. The resulting exposure to air pollution causes
      an estimated 4.5% of the global burden of disease. Large variability and a lack
      of resources for research and development have resulted in highly uncertain
      exposure estimates. OBJECTIVE: We sought to identify research priorities for
      exposure assessment that will more accurately and precisely define exposure
      response relationships of household air pollution necessary to inform future
      cleaner-burning cookstove dissemination programs. DATA SOURCES: As part of an
      international workshop in May 2011, an expert group characterized the state of
      the science and developed recommendations for exposure assessment of household
      air pollution. SYNTHESIS: The following priority research areas were identified
      to explain variability and reduce uncertainty of household air pollution exposure
      measurements: improved characterization of spatial and temporal variability for
      studies examining both short- and long-term health effects; development and
      validation of measurement technology and approaches to conduct complex exposure
      assessments in resource-limited settings with a large range of pollutant
      concentrations; and development and validation of biomarkers for estimating dose.
      Addressing these priority research areas, which will inherently require an
      increased allocation of resources for cookstove research, will lead to better
      characterization of exposure-response relationships. CONCLUSIONS: Although the
      type and extent of exposure assessment will necessarily depend on the goal and
      design of the cookstove study, without improved understanding of exposure
      response relationships, the level of air pollution reduction necessary to meet
      the health targets of cookstove interventions will remain uncertain.

PMID- 23872399
TI  - Riluzole attenuates the effects of chemoconvulsants acting on glutamatergic and
      GABAergic neurotransmission in the planarian Dugesia tigrina.
AB  - Planarians, the non-parasitic flatworms, display dose-dependent, distinct (C-like
      and corkscrew-like) hyperkinesias upon exposure to 0.001-10 mM aqueous solutions
      of glutamatergic agonists (L-glutamate and N-methyl-D-aspartate (NMDA)) and 0.001
      5 mM concentrations of the glutamate decarboxylase (GAD) inhibitor
      (semicarbazide). In the planarian seizure-like activity (PSLA) experiments the
      three chemoconvulsants displayed the following order of potency (EC50): L
      glutamate (0.6mM)>NMDA (1.4 mM)>semicarbazide (4.5mM). Planarian hyperkinesias
      behavior counting experiments also revealed that riluzole (0.001 to 1mM), an anti
      convulsive agent, displayed no significant behavioral activity by itself, but
      attenuated hyperkinesias elicited by the three chemoconvulsants targeting either
      glutamatergic or GABAergic neurotransmission with the following order of potency
      (IC50): NMDA (44.7 uM)>semicarbazide (88.3 uM)>L-glutamate (160 uM). Further, (+)
      MK-801, a specific NMDA antagonist, alleviated 3mM NMDA (47%) or 3mM L-glutamate
      (27%) induced planarian hyperkinesias. The results provide pharmacological
      evidence for the presence of glutamatergic receptor-like and semicarbazide
      sensitive functional GAD enzyme-like proteins in planaria in addition to
      demonstrating, for the first time, the anti-convulsive effects of riluzole in an
      invertebrate model. High performance liquid chromatography coupled with
      fluorescence detection (HPLC-F) analysis performed on planarian extracts post no
      drug treatment (control) or treatment with 3mM semicarbazide, combination of 3mM
      semicarbazide and 0.1 mM riluzole, or 0.1 mM riluzole revealed that 3 mM
      semicarbazide induced 35% decrease in the GABA levels and a combination of 3mM
      semicarbazide and 0.1 mM riluzole induced 42% decrease in glutamate levels with
      respect to the control group.

PMID- 23872400
TI  - Dopamine D(3) receptor as a new pharmacological target for the treatment of
      depression.
AB  - A substantial proportion of depressed patients do not respond to current
      antidepressant drug therapies. So far, antidepressant drugs have been developed
      based on the "monoaminergic hypothesis" of depression, which considers a synaptic
      deficiency in 5-hydroxytryptamine (5-HT; serotonin) or noradrenaline as main
      cause. More recently, the dopaminergic system has been implicated in the efficacy
      of some antidepressants, such as desipramine, amineptine, nomifensine.
      Dysfunction of dopaminergic neurotransmission within the mesolimbic system may
      contribute to anhedonia, loss of motivation and psychomotor retardation in severe
      depressive disorders. Dopamine D3 receptor subtype is located both pre- and
      postsynaptically in brain areas regulating motivation and reward-related behavior
      and has been implicated in depression-like behaviors. Activity of mesolimbic
      dopamine neurons in the reward circuit is a key determinant of behavioral
      susceptibility/resilience to chronic stress, which plays a central role in the
      pathogenesis of depression. Dopamine D3 receptor expression and function are both
      down-regulated in stress and depression, and these changes are reversed by
      antidepressant treatments, suggesting that enhanced dopaminergic
      neurotransmission mediated by dopamine D3 receptor participates in adaptive
      changes related to antidepressant activity. Of note, brain derived neurotrophic
      factor (BDNF) controls the expression of the dopamine D3 receptor in some brain
      areas and BDNF induction by antidepressant treatments is related to their
      behavioral activity. A number of experimental drugs in pre-clinical or clinical
      development, including aripiprazole and cariprazine, may act as antidepressants
      because of their partial agonist activity at dopamine D3 receptors. These
      preclinical and clinical data are discussed in the present review. 

PMID- 23872401
TI  - Enhancement of PLGF production by 15-(S)-HETE via PI3K-Akt, NF-kappaB and COX-2
      pathways in rheumatoid arthritis synovial fibroblast.
AB  - Metabolites from arachidonic acids play the pivotal roles in inflammatory
      arthritis. Arachidonic acid could be metabolized by cyclooxygenase (COX) and
      lipoxygenase (LOX) to produce the bioactive eicosanoids. Although the down-stream
      products of COX including prostaglandin E2 are well-known inflammatory
      stimulators, the role of LOX products in inflammatory arthritis is still unclear.
      Here we found that the downstream product of 15-LOX, 15-S-hydroxyeicosatetraenoic
      acid (15-(S)-HETE), can enhance the expression of placenta growth factor (PLGF),
      which is recently considered to play an important role in rheumatoid arthritis.
      15-(S)-HETE increased the expression of PLGF in human rheumatoid arthritis
      synovial fibroblasts in a time-dependent and concentration-dependent manner. PI3K
      Akt, NF-kappaB signaling pathways were involved in the potentiation effects of 15
      (S)-HETE. In addition, COX-2 was up-regulated by the treatment of 15-(S)-HETE and
      the increase of COX-2 expression participated in 15-(S)-HETE-induced PLGF
      expression, which was confirmed by COX-2 shRNA or pharmacological COX-2
      inhibitor. Moreover, it was found that treatment of prostaglandin E2 (PGE2),
      which was the main down-stream metabolite of COX-2, increased the expression of
      PLGF. EP1, EP2, EP3 and EP4 agonists could up-regulate PLGF as well. In animal
      studies, we found that the adjuvant-induced expression of PLGF and COX-2 was
      inhibited in 15-LOX knockout mice. These results indicated that PLGF up
      regulation by 15-LOX downstream product may be involved in inflammatory
      arthritis. 

PMID- 23872403
TI  - Gene therapy approaches to enhance regeneration of the injured peripheral nerve.
AB  - Peripheral nerve injury in humans often leads to incomplete functional recovery.
      In this review we discuss the potential for gene therapy to be used as a strategy
      alongside surgical repair techniques for the study of peripheral nerve
      regeneration in rodent models and with a view to its eventual use for the
      promotion of successful regeneration in the clinic. Gene therapy can be defined
      as the introduction of a foreign, therapeutic gene into living cells in order to
      treat a disease. The first attempts to express a foreign gene in peripheral
      neurons date back more than 25 years. The vectors used at that time were
      imperfect-mainly because they contained viral genes that were expressed in the
      target cells and elicited an immunological response. Fortunately significant
      progress has been made: today adeno-associated viral vectors can be produced
      completely free of viral genes and Phase I and II clinical studies have shown
      that these vectors are well tolerated. The technology for gene delivery has
      reached a state of readiness for clinical translation in many fields of
      neurology, including peripheral nerve repair. The current range of potential
      therapeutic genes for the repair of the traumatized peripheral nerve has also
      grown over the years and now includes neurotrophic factors with specificities for
      various subtypes of peripheral neurons, cell adhesion and extracellular matrix
      molecules and transcription factors. This review for this Festschrift, published
      to celebrate the 70th birthday of Willem Hendrik Gispen, contains many
      "footprints" from the time the senior author (JV) worked with Willem Hendrik,
      first as a student intern, then as a Ph.D. student (1983-1987) and later as a
      postdoctoral fellow (1989-1993). The preface of this article highlights personal
      memories of a time that will never come back. 

PMID- 23872404
TI  - Contactins in the neurobiology of autism.
AB  - Autism is a disease of brain plasticity. Inspiring work of Willem Hendrik Gispen
      on neuronal plasticity has stimulated us to investigate gene defects in autism
      and the consequences for brain development. The central process in the
      pathogenesis of autism is local dendritic mRNA translation which is dependent on
      axodendritic communication. Hence, most autism-related gene products (i) are part
      of the protein synthesis machinery itself, (ii) are components of the mTOR signal
      transduction pathway, or (iii) shape synaptic activity and plasticity.
      Accordingly, prototype drugs have been recognized that interfere with these
      pathways. The contactin (CNTN) family of Ig cell adhesion molecules (IgCAMs)
      harbours at least three members that have genetically been implicated in autism:
      CNTN4, CNTN5, and CNTN6. In this chapter we review the genetic and
      neurobiological data underpinning their role in normal and abnormal development
      of brain systems, and the consequences for behavior. Although data on each of
      these CNTNs are far from complete, we tentatively conclude that these three
      contactins play roles in brain development in a critical phase of establishing
      brain systems and their plasticity. They modulate neuronal activities, such as
      neurite outgrowth, synaptogenesis, survival, guidance of projections and terminal
      branching of axons in forming neural circuits. Current research on these CNTNs
      concentrate on the neurobiological mechanism of their developmental functions. A
      future task will be to establish if proposed pharmacological strategies to
      counteract ASD-related symptomes can also be applied to reversal of phenotypes
      caused by genetic defects in these CNTN genes. 

PMID- 23872405
TI  - Melanocortin MC(4) receptor-mediated feeding and grooming in rodents.
AB  - Decades ago it was recognized that the pharmacological profile of melanocortin
      ligands that stimulated grooming behavior in rats was strikingly similar to that
      of Xenopus laevis melanophore pigment dispersion. After cloning of the
      melanocortin MC1 receptor, expressed in melanocytes, and the melanocortin MC4
      receptor, expressed mainly in brain, the pharmacological profiles of these
      receptors appeared to be very similar and it was demonstrated that these
      receptors mediate melanocortin-induced pigmentation and grooming respectively.
      Grooming is a low priority behavior that is concerned with care of body surface.
      Activation of central melanocortin MC4 receptors is also associated with meal
      termination, and continued postprandial stimulation of melanocortin MC4 receptors
      may stimulate natural postprandial grooming behavior as part of the behavioral
      satiety sequence. Indeed, melanocortins fail to suppress food intake or induce
      grooming behavior in melanocortin MC4 receptor-deficient rats. This review will
      focus on how melanocortins affect grooming behavior through the melanocortin MC4
      receptor, and how melanocortin MC4 receptors mediate feeding behavior. This
      review also illustrates how melanocortins were the most likely candidates to
      mediate grooming and feeding based on the natural behaviors they induced. 

PMID- 23872402
TI  - Hippocampal calcium dysregulation at the nexus of diabetes and brain aging.
AB  - Recently it has become clear that conditions of insulin resistance/metabolic
      syndrome, obesity and diabetes, are linked with moderate cognitive impairment in
      normal aging and elevated risk of Alzheimer's disease. It appears that a common
      feature of these conditions is impaired insulin signaling, affecting the brain as
      well as peripheral target tissues. A number of studies have documented that
      insulin directly affects brain processes and that reduced insulin signaling
      results in impaired learning and memory. Several studies have also shown that
      diabetes induces Ca(2+) dysregulation in neurons. Because brain aging is
      associated with substantial Ca(2+) dyshomeostasis, it has been proposed that
      impaired insulin signaling exacerbates or accelerates aging-related Ca(2+)
      dyshomeostasis. However, there have been few studies examining insulin
      interactions with Ca(2+) regulation in aging animals. We have been testing
      predictions of the Ca(2+) dysregulation/diabetes/brain aging hypothesis and have
      found that insulin and insulin-sensitizers (thiazolidinediones) target several
      hippocampal Ca(2+)-related processes affected by aging. The drugs appear able to
      reduce the age-dependent increase in Ca(2+) transients and the Ca(2+) -sensitive
      afterhyperpolarization. Thus, while additional testing is needed, the results to
      date are consistent with the view that strategies that enhance insulin signaling
      can counteract the effect of aging on Ca(2+) dysregulation. 

PMID- 23872406
TI  - The role of melanocortins and Neuropeptide Y in food reward.
AB  - The Neuropeptide Y and the melanocortin peptides are two well-described
      hypothalamic feeding peptides regulating energy balance. Predominantly expressed
      within the arcuate nucleus, these neurons project to different brain areas and
      modulate various aspects of feeding. Hedonic feeding, where one overindulges in
      palatable food consumption beyond one's nutritional necessities, is one such
      aspect regulated by NPY/melanocortin signaling. Research suggests that
      NPY/melanocortin regulate hedonic aspects of feeding through its projections to
      the brain reward circuitry (ventral tegmental area, lateral hypothalamus, nucleus
      accumbens etc.), however, exact target areas have not yet been identified. The
      current work explores literature to provide a mechanistic explanation for the
      effects of these peptides on food reward. 

PMID- 23872407
TI  - Diabetes mellitus- and ageing-induced changes in the capacity for long-term
      depression and long-term potentiation inductions: toward a unified mechanism.
AB  - Long-lasting type 1 and type 2 diabetes mellitus (DM) are both associated with
      impaired cognitive function in humans. Animal models of DM have confirmed the
      detrimental effect of high blood glucose levels on learning and memory. What are
      the neural correlates of such impaired cognition? It is widely, although not
      universally, believed that long-lasting increase and decrease in synaptic
      strength, known as long-term potentiation (LTP) and depression (LTD), provide an
      important key to understanding the cellular and molecular mechanisms by which
      memories are formed and stored. The majority of animal studies that examined the
      effect of DM on LTD and LTP used the streptozotocin (STZ) rodent model of type 1
      DM, with the exception of a few that used genetic models of type 2 DM. Studies in
      STZ-DM rodents show that cellular processes underlying synapse strengthening or
      weakening are not altered. Rather, the capacity for LTP induction is reduced
      whereas that for LTD induction is enhanced. The mechanisms underlying DM-related
      changes in LTD and LTP inductions are still unknown. However, that the levels of
      effective postsynaptic depolarization for LTD and LTP inductions are
      concomitantly shifted in opposite directions put constraints on them. Moreover,
      that DM-, metaplasticity-, stress- and ageing-related changes in LTD and LTP
      inductions exhibit the very same phenomenology suggests that they might involve
      common mechanisms. Dissecting out the mechanisms responsible for DM-related
      changes in the capacity for LTD and LTP inductions is helping to improve
      treatment of impaired cognitive function in DM patients. 

PMID- 23872408
TI  - Mutations of the synapse genes and intellectual disability syndromes.
AB  - Intellectual disability syndromes have been found associated to numerous mutated
      genes that code for proteins functionally involved in synapse formation, the
      regulation of dendritic spine morphology, the regulation of the synaptic
      cytoskeleton or the synthesis and degradation of specific synapse proteins. These
      studies have strongly demonstrated that even mild alterations in synapse
      morphology and function give rise to mild or severe alteration in intellectual
      abilities. Interestingly, pharmacological agents that are able to counteract
      these morphological and functional synaptic anomalies can also improve the
      symptoms of some of these conditions. This review is summarizing recent
      discoveries on the functions of some of the genes responsible for intellectual
      disability syndromes connected with synapse dysfunctions. 

PMID- 23872409
TI  - Sweet memories: 20 years of progress in research on cognitive functioning in
      diabetes.
AB  - This paper appears in a special issue of the European Journal of Pharmacology
      that commemorates the retirement of Professor Willem Hendrik Gispen as
      distinguished professor of Utrecht University and as editor of the European
      Journal of Pharmacology. The paper provides an overview of a research line on the
      impact of diabetes on cognition that we started together 20 years ago, and that
      continues to this day. I will report how we more or less stumbled upon this
      topic, that was understudied, but proved to be of definite clinical relevance. I
      will discuss how we tried to establish animal models, how developments from
      clinical and experimental studies from around the world led us to reconsider our
      concepts, and how findings from research on diabetic neuropathy, insulin
      signaling in the brain, Alzheimer's disease and dementia, and vascular disease
      and stroke converged and helped to create new ideas and refute others. This
      voyage has not ended yet, because the ultimate goal is to offer patients with
      diabetes treatment that can protect them against accelerated cognitive decline.
      Although this could take another 20 years, the research from Willem Hendrik and
      his group brought us an important step in the right direction. 

PMID- 23872410
TI  - Optical imaging of structural and functional synaptic plasticity in vivo.
AB  - The adult brain has long been viewed as a collection of neuronal networks that
      maintain a fixed configuration of synaptic connections. Brain plasticity and
      learning was thought to depend exclusively on changes in the gain and offset of
      these connections. Over the last 50 years, molecular and cellular studies of
      neuroplasticity have altered this view. Brain plasticity is now viewed as a
      continuum of structural changes that could vary from long-range axon growth to
      the twitching of dendritic spines and synaptic receptor composition dynamics.
      Plasticity proteins similar to those that drive neuronal development may underpin
      brain plasticity, and consequently could regulate adaptations to new experiences
      and learning. In vivo imaging has confirmed that neuronal plasticity in the adult
      brain involves subtle structural changes at synaptic connections, including
      synapse formation and pruning. Synaptic structural changes are associated with
      experience-dependent plasticity, learning, brain traumas and neurodegeneration.
      Owing to the expanding toolbox of in vivo imaging we have come to the brink of
      understanding the causal relationship between structural synaptic network
      dynamics and functional brain plasticity. This review summarizes the technical
      developments in the imaging of laboratory animals' brains in vivo and the
      insights they have provided into the mechanisms of brain plasticity and learning.

PMID- 23872412
TI  - Pathogenesis of diabetic neuropathy: focus on neurovascular mechanisms.
AB  - Neuropathies of the peripheral and autonomic nervous systems affect up to half of
      all people with diabetes, and are major risk factors for foot ulceration and
      amputation. The aetiology is multifactorial: metabolic changes in diabetes may
      directly affect neural tissue, but importantly, neurodegenerative changes are
      precipitated by compromised nerve vascular supply. Experiments in animal models
      of diabetic neuropathy suggest that similar metabolic sequelae affect neurons and
      vasa nervorum endothelium. These include elevated polyol pathway activity,
      oxidative stress, the formation of advanced glycation and lipoxidation end
      products, and various pro-inflammatory changes such as elevated protein kinase C,
      nuclear factor kappaB and p38 mitogen activated protein kinase signalling. These
      mechanisms do not work in isolation but strongly interact in a mutually
      facilitatory fashion. Nitrosative stress and the induction of the enzyme poly
      (ADP-ribose) polymerase form one important link between physiological stressors
      such as reactive oxygen species and the pro-inflammatory mechanisms. Recently,
      evidence points to endoplasmic stress and the unfolded protein response as
      forming another crucial link. This review focuses on the aetiopathogenesis of
      neurovascular changes in diabetic neuropathy, elucidated in animal studies, and
      on putative therapeutic targets the majority of which have yet to be tested for
      efficacy in clinical trials. 

PMID- 23872411
TI  - Ileal apical sodium-dependent bile acid transporter protein levels are down
      regulated through ubiquitin-dependent protein degradation induced by bile acids.
AB  - The ileal apical sodium-dependent bile acid transporter (ASBT or SLC10A2) has a
      crucial role in intestinal bile acid absorption. We previously reported that
      enterobacteria-mediated bile acid conversion was involved in the alteration of
      ileal ASBT expression levels. In the present study, to investigate the hypothesis
      that ileal ASBT protein levels are post-translationally regulated by
      enterobacteria-associated bile acids, alteration of ileal ASBT protein levels was
      analysed in mice 12 h and 24 h after anti-bacterial drug ampicillin (ABPC)
      treatment (100 mg/kg, single shot) that altered bile acid composition in the
      intestinal lumen. In ABPC-treated mice, enterobacteria-biotransformed bile acid,
      taurodeoxycholic acid (TDCA) and cholic acid (CA) levels were decreased, whereas
      taurocholic acid (TCA) and tauro-beta-muricholic acid levels were increased in
      the intestinal lumen. Ileal ASBT protein levels in brush-border membrane vesicles
      (BBMVs), but not ileal Asbt mRNA levels, were significantly increased in the ABPC
      treated mice, and the extent of ubiquitination of the ileal ASBT protein was
      reduced in the ABPC-treated mice. Treatment of ABPC-pretreated mice with CA or
      TDCA, but not TCA, significantly decreased ileal ASBT protein levels and
      increased the extent of ubiquitination of ileal ASBT protein. Treatment of mice
      with the lysosome inhibitor, chloroquine, or the proteasome inhibitor, MG132,
      increased ileal ASBT protein levels in BBMVs. CA-mediated reduction of ASBT
      protein levels in the ABPC-pretreated mice was attenuated by co-treatment with
      chloroquine or MG132. These results suggest that ileal ASBT protein is degraded
      by a ubiquitin-dependent pathway in response to enterobacteria-associated bile
      acids.

PMID- 23872413
TI  - A human rights view on access to controlled substances for medical purposes under
      the international drug control framework.
AB  - The world is confronted with a major public health deficit caused by poor access
      to controlled essential medicines under the international drug control framework.
      This is affecting millions of patients on a daily basis and resulting in numerous
      human rights violations. The present review contextualises this deficit from a
      human rights perspective. Drug control efforts are informed by a twofold
      objective stemming from the double nature of scheduled substances: free access
      for medical purposes should be ensured, though non-medical use of substances such
      as opium should be restricted. The international drug control framework is, in
      theory, based on this twofold notion, however at the level of interpretation,
      monitoring, and implementation, a one-sided emphasis is demonstrated. By tracing
      a parallel between the obligations of states under the international drug control
      framework and those that derive from human rights law, the review shows that the
      two systems seem incoherent and conflicting in nature and flags the importance of
      cross-disciplinary research into drug control and human rights. 

PMID- 23872414
TI  - Resident adult neural stem cells in Parkinson's disease--the brain's own repair
      system?
AB  - One important pathological process in the brain of Parkinson disease (PD)
      patients is the degeneration of the dopaminergic neurons in the substantia nigra,
      which leads to a decline in striatal dopamine levels and motor dysfunction. A
      major clinical problem is that this degenerative process currently cannot be
      stopped or reversed. Expectations from the restorative capacity of neural stem
      cells (NSCs) are high, as these cells can potentially replace the degenerating
      neurons. The discovery of the presence of NSCs in the adult human brain has
      instigated research into the potential of these cells as a resource to promote
      brain repair in neurodegenerative diseases. Neural stem and progenitor cells
      reside in the subventricular zone (SVZ), which is closely situated to the
      striatum, which is affected in PD. Therefore, restoring the dopamine levels in
      the striatum of PD patients through stimulating endogenous NSCs in the nearby SVZ
      to migrate into the striatum and differentiate into dopaminergic neurons might
      thus be an attractive future therapeutic approach. We will review the reported
      changes in NSCs in the SVZ of PD animal models and PD patients, which are due to
      a lack of striatal dopamine. Furthermore, we will summarise the reports that
      describe efforts to stimulate NSCs to replace dopaminergic cells in the SN and
      restore striatal dopamine levels. In our opinion, mobilizing the endogenous SVZ
      NSCs to replenish striatal dopamine is an attractive approach to alleviate the
      motor symptoms in PD patients, without the ethical and immunological challenges
      of transplantation of NSCs and foetal brain tissue. 

PMID- 23872415
TI  - Glutamatergic receptors at developing synapses: the role of GluN3A-containing
      NMDA receptors and GluA2-lacking AMPA receptors.
AB  - During brain development excitatory synapses exhibit significant changes in their
      postsynaptic receptors and activated signaling pathways. Calcium represents the
      most crucial signaling factor in synaptic transmission and plasticity. Therefore
      developmental changes in calcium-permeable channels on the membrane contribute
      significantly to the modulation of neurotransmission at excitatory synapses. The
      present review focuses on two types of "non-canonical" glutamate receptors in
      terms of calcium permeability: GluN3A-containing NMDA receptors (calcium
      impermeable) and GluA2-lacking AMPA receptors (calcium permeable). The
      involvement of these receptors during development and their potential function in
      synaptic plasticity are discussed. The synaptic incorporation of these receptors
      would alter calcium permeability, and therefore the threshold/direction of
      further plastic changes. We believe that characterizing the dynamics of non
      canonical glutamate receptors during development could provide insight into how
      these receptors are recruited or removed in pathological conditions. 

PMID- 23872416
TI  - "Are melanocortin receptors constitutively active in vivo?".
AB  - Constitutive activity is defined as ligand-independent activity, resulting in the
      production of a second messenger, even in the absence of an agonist. There has
      been widespread acceptance of the concept of G-protein-coupled receptor
      constitutive activity, with this activity specifically blocked by inverse
      agonists, a particular class of ligands often previously characterised as merely
      antagonists. The melanocortin receptors are highly unusual because their
      physiological activity is mediated not by a single ligand but by a number of
      endogenous peptide ligands, with the ability to exhibit agonist, antagonist or
      potentially inverse agonist behaviour. It remains more contentious to what extent
      the demonstrable constitutive activity of melanocortin receptors, particularly
      those expressed within the central nervous system, has in (patho)physiological
      processes. This review examines evidence from animal and laboratory based
      studies, focussing particularly upon peripherally expressed melanocortin-1
      receptors and centrally expressed melanocortin-4 receptors, to consider how
      recent insights into both receptor structure itself and the molecules know to
      play a role in melanocortin signalling continue to shape our understanding of
      melanocortin biology. 

PMID- 23872417
TI  - Modulation of NMDA receptor at the synapse: promising therapeutic interventions
      in disorders of the nervous system.
AB  - There is general agreement that excessive activation of N-methyl-D-aspartate
      (NMDA) receptors plays a key role in mediating at least some aspects of synaptic
      dysfunction in several central nervous system disorders. On this view, in the
      last decades, research focused on the discovery of different compounds able to
      reduce NMDA receptor activity, such as classical and/or subunit-specific
      antagonists. However, the increasing body of knowledge on specific signaling
      pathways downstream NMDA receptors led to the identification of new
      pharmacological targets for NMDA receptor-related pathological conditions.
      Moreover, besides over-activation, several studies indicated that also abnormal
      NMDA receptor trafficking, resulting in the modification of the receptor subunit
      composition at the synapse, has a major role in the pathogenesis of several brain
      disorders. For this reason, the discovery of the molecular mechanisms regulating
      the abundance of synaptic versus extra-synaptic NMDA receptors as well as the
      activation of the specific signaling pathways downstream the different NMDA
      receptor subtypes is needed for the development of novel therapeutic approaches
      for NMDA receptor-dependent synaptic dysfunction. 

PMID- 23872418
TI  - Sumoylation regulates nuclear localization and function of zinc finger
      transcription factor ZIC3.
AB  - ZIC3, an X-linked zinc finger transcription factor, was the first identified gene
      involved in establishing normal left-right patterning in humans. Mutations in the
      Zic3 gene in patients cause heterotaxy, which includes congenital heart defects.
      However, very little is known about how the function of the ZIC3 protein is
      regulated. Sumoylation is a posttranslational modification process in which a
      group of small ubiquitin-like modifier (SUMO) proteins is covalently attached to
      targets via a series of enzymatic reactions. Here, we report for the first time
      that sumoylation targets human ZIC3 primarily on the consensus lysine residue
      K248, which is critical for the nuclear retention of ZIC3. Consequently, SUMO
      modification potentiates the repressive activity of ZIC3 on the promoter of its
      target gene cardiac alpha-actin, and the mutation of lysine 248 to arginine
      (K248R) abolishes its repressive function. We further revealed that ZIC3 variants
      with mutations found in human patients with congenital anomalies exhibit aberrant
      sumoylation activity, which at least partially accounts for their cytoplasmic
      diffusion. Improved sumoylation of human disease-associated ZIC3 variants
      reestablishes their nuclear occupancy in the presence of SUMO E3 ligase and SUMO
      1. Thus, the altered sumoylation status of ZIC3 underpins the developmental
      abnormalities associated with these ZIC3 mutants. The SUMO targeting consensus
      sequence in ZIC3 is highly conserved in its paralogs and orthologs, pointing to
      sumoylation as a general mechanism underlying the functional control of ZIC
      proteins. This study provides a potential therapeutic strategy to regain the
      normal subcellular distribution and function of ZIC3 mutants by restoring SUMO
      conjugation. 

PMID- 23872419
TI  - Calix[6]arene bypasses human pancreatic cancer aggressiveness: downregulation of
      receptor tyrosine kinases and induction of cell death by reticulum stress and
      autophagy.
AB  - Pancreatic cancer ranks fourth among cancer-related causes of death in North
      America. Minimal progress has been made in the diagnosis and treatment of
      patients with late-stage tumors. Moreover, pancreatic cancer aggressiveness is
      closely related to high levels of pro-survival mediators, which can ultimately
      lead to rapid disease progression, resistance and metastasis. The main goal of
      this study was to define the mechanisms by which calix[6]arene, but not other
      calixarenes, efficiently decreases the aggressiveness of a drug resistant human
      pancreas carcinoma cell line (Panc-1). Calix[6]arene was more potent in reducing
      Panc-1 cell viability than gemcitabine and 5-fluorouracil. In relation to the
      underlying mechanisms of cytotoxic effects, it led to cell cycle arrest in the
      G0/G1 phase through downregulation of PIM1, CDK2, CDK4 and retinoblastoma
      proteins. Importantly, calix[6]arene abolished signal transduction of Mer and AXL
      tyrosine kinase receptors, both of which are usually overexpressed in pancreatic
      cancer. Accordingly, inhibition of PI3K and mTOR was also observed, and these
      proteins are positively modulated by Mer and AXL. Despite decreasing the
      phosphorylation of AKT at Thr308, calix[6]arene caused an increase in
      phosphorylation at Ser473. These findings in conjunction with increased BiP and
      IRE1-alpha provide a molecular basis explaining the capacity of calix[6]arene to
      trigger endoplasmic reticulum stress and autophagic cell death. Our findings
      highlight calix[6]arene as a potential candidate for overcoming pancreatic cancer
      aggressiveness. Importantly, we provide evidence that calix[6]arene affects a
      broad array of key targets that are usually dysfunctional in pancreatic cancer, a
      highly desirable characteristic for chemotherapeutics. 

PMID- 23872420
TI  - Post-translational membrane insertion of an endogenous YidC substrate.
AB  - Membrane protein insertion is controlled by proteinaceous factors embedded in the
      lipid bilayer. Bacterial inner membrane proteins utilise the Sec translocon as
      the major facilitator of insertion; however some proteins are Sec independent and
      instead require only YidC. A common feature of YidC substrates is the exposure of
      a signal anchor sequence when translation is close to completion; this allows
      minimal time for targeting and favours a post-translational insertion mechanism.
      Despite this there is little evidence of YidC's post-translational activity. Here
      we develop an experimental system that uncouples translation and insertion of the
      endogenous YidC substrate F0c (subunit c of the F0F1 ATP synthase). In this
      process we (i) develop a novel one step purification method for YidC, including
      an on column membrane reconstitution, (ii) isolate a soluble form of F0c and
      (iii) show that incubation of F0c with YidC proteoliposomes results in a high
      level of membrane integration. Conformational analyses of inserted F0c through
      Blue Native PAGE and fluorescence quenching reveal a native, oligomerised
      structure. These data show that YidC can act as a post-translational insertase, a
      finding which could explain the absence of a ribosome binding domain on YidC.
      This correlates with the post-translational activity of other YidC family members
      lacking the ribosome binding domain. 

PMID- 23872421
TI  - GDNF family ligand dependent STAT3 activation is mediated by specific
      alternatively spliced isoforms of GFRalpha2 and RET.
AB  - Neurturin (NRTN), a member of the GDNF family of ligands (GFL), is currently
      investigated in a series of clinical trials for Parkinson's disease. NRTN signals
      through its cognate receptor GFRalpha2 and co-receptor RET to induce neurite
      outgrowth, but the underlying mechanism remains to be better understood. STAT3
      was previously shown to be activated by oncogenic RET, independent of ligand and
      GFRalpha. In this study, we demonstrated that NRTN induced serine(727) but not
      tyrosine(705) phosphorylation of STAT3 in primary cortical neuron and neuronal
      cell lines. Remarkably, STAT3 phosphorylation was found to be mediated
      specifically by GFRalpha2c and RET9 isoforms. Furthermore, serine but not
      tyrosine dominant negative mutant of STAT3 impaired NRTN induced neurite
      outgrowth, indicative of the role of STAT3 as a downstream mediator of NRTN
      function. Similar to NGF, the NRTN induced P-Ser-STAT3 was localized to the
      mitochondria but not to the nucleus. Mitochondrial STAT3 was further found to be
      intimately involved in NRTN induced neurite outgrowth. Collectively, these
      findings demonstrated the hitherto unrecognized and novel role of specific
      GFRalpha2 and RET isoforms in mediating NRTN activation of STAT3 and the
      transcription independent mechanism whereby the mitochondria localized P-Ser
      STAT3 mediated NRTN induced neurite outgrowth. 

PMID- 23872422
TI  - 1,8-Cineol inhibits nuclear translocation of NF-kappaB p65 and NF-kappaB
      dependent transcriptional activity.
AB  - Natural plant-derived products are commonly applied to treat a broad range of
      human diseases, including cancer as well as chronic and acute airway
      inflammation. In this regard, the monoterpene oxide 1,8-cineol, the active
      ingredient of the clinically approved drug Soledum(r), is well-established for
      the therapy of airway diseases, such as chronic sinusitis and bronchitis, chronic
      obstructive pulmonary disease and bronchial asthma. Although clinical trials
      underline the beneficial effects of 1,8-cineol in treating inflammatory diseases,
      the molecular mode of action still remains unclear. Here, we demonstrate for the
      first time a 1,8-cineol-depending reduction of NF-kappaB-activity in human cell
      lines U373 and HeLa upon stimulation using lipopolysaccharides (LPS).
      Immunocytochemistry further revealed a reduced nuclear translocation of NF-kappaB
      p65, while qPCR and western blot analyses showed strongly attenuated expression
      of NF-kappaB target genes. Treatment with 1,8-cineol further led to increased
      protein levels of IkappaBalpha in an IKK-independent matter, while FRET-analyses
      showed restoring of LPS-associated loss of interaction between NF-kappaB p65 and
      IkappaBalpha. We likewise observed reduced amounts of phosphorylated c-Jun N
      terminal kinase 1/2 protein in U373 cells after exposure to 1,8-cineol. In
      addition, 1,8-cineol led to decreased amount of nuclear NF-kappaB p65 and
      reduction of its target gene IkappaBalpha at protein level in human peripheral
      blood mononuclear cells. Our findings suggest a novel mode of action of 1,8
      cineol through inhibition of nuclear NF-kappaB p65 translocation via IkappaBalpha
      resulting in decreased levels of proinflammatory NF-kappaB target genes and may
      therefore broaden the field of clinical application of this natural drug for
      treating inflammatory diseases. 

PMID- 23872423
TI  - The complexity of recognition of ubiquitinated substrates by the 26S proteasome.
AB  - The Ubiquitin Proteasome System (UPS) was discovered in two steps. Initially, APF
      1 (ATP-dependent proteolytic Factor 1) later identified as ubiquitin (Ub), a
      hitherto known protein of unknown function, was found to covalently modify
      proteins. This modification led to degradation of the tagged protein by - at that
      time - an unknown protease. This was followed later by the identification of the
      26S proteasome complex which is composed of a previously identified Multi
      Catalytic Protease (MCP) and an additional regulatory complex, as the protease
      that degrades Ub-tagged proteins. While Ub conjugation and proteasomal
      degradation are viewed as a continued process responsible for most of the
      regulated proteolysis in the cell, the two processes have also independent roles.
      In parallel and in the years that followed, the hallmark signal that links the
      substrate to the proteasome was identified as an internal Lys48-based polyUb
      chain. However, since these initial findings were described, our understanding of
      both ends of the process (i.e. Ub-conjugation to proteins, and their recognition
      and degradation), have advanced significantly. This enabled us to start bridging
      the ends of this continuous process which suffered until lately from limited
      structural data regarding the 26S proteasomal architecture and the structure and
      diversity of the Ub chains. These missing pieces are of great importance because
      the link between ubiquitination and proteasomal processing is subject to numerous
      regulatory steps and are found to function improperly in several pathologies.
      Recently, the molecular architecture of the 26S proteasome was resolved in great
      detail, enabling us to address mechanistic questions regarding the various
      molecular events that polyubiquitinated (polyUb) substrates undergo during
      binding and processing by the 26S proteasome. In addition, advancement in
      analytical and synthetic methods enables us to better understand the structure
      and diversity of the degradation signal. The review summarizes these recent
      findings and addresses the extrapolated meanings in light of previous reports.
      Finally, it addresses some of the still remaining questions to be solved in order
      to obtain a continuous mechanistic view of the events that a substrate undergoes
      from its initial ubiquitination to proteasomal degradation. This article is part
      of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas
      Sommer and Dieter H. Wolf. 

PMID- 23872424
TI  - Tobacco industry tangos with descriptor ban in Malaysia.

PMID- 23872425
TI  - Investigating oxidative stress and inflammatory responses elicited by silver
      nanoparticles using high-throughput reporter genes in HepG2 cells: effect of
      size, surface coating, and intracellular uptake.
AB  - Silver nanoparticles (Ag NP) have been shown to generate reactive oxygen species;
      however, the association between physicochemical characteristics of nanoparticles
      and cellular stress responses elicited by exposure has not been elucidated. Here,
      we examined three key stress-responsive pathways activated by Nrf-2/ARE,
      NFkappaB, and AP1 during exposure to Ag NP of two distinct sizes (10 and 75 nm)
      and coatings (citrate and polyvinylpyrrolidone), as well as silver nitrate
      (AgNO3), and CeO2 nanoparticles. The in vitro assays assessed the cellular
      response in a battery of stable luciferase-reporter HepG2 cell lines. We further
      assessed the impact of Ag NP and AgNO3 exposure on cellular redox status by
      measuring glutathione depletion. Lastly, we determined intracellular Ag
      concentration by inductively coupled plasma mass spectroscopy (ICP-MS) and re
      analyzed reporter-gene data using these values to estimate the relative potencies
      of the Ag NPs and AgNO3. Our results show activation of all three stress response
      pathways, with Nrf-2/ARE displaying the strongest response elicited by each Ag NP
      and AgNO3 evaluated here. The smaller (10-nm) Ag NPs were more potent than the
      larger (75-nm) Ag NPs in each stress-response pathway, and citrate-coated Ag NPs
      had higher intracellular silver concentrations compared with both PVP-coated Ag
      NP and AgNO3. The cellular stress response profiles after Ag NP exposure were
      similar to that of AgNO3, suggesting that the oxidative stress and inflammatory
      effects of Ag NP are likely due to the cytotoxicity of silver ions.

PMID- 23872426
TI  - Developmental stage dependent neural stem cells sensitivity to methylmercury
      chloride on different biofunctional surfaces.
AB  - Sensitivity of neural stem cells viability, proliferation and differentiation
      upon exposure to methylmercury chloride (MeHgCl) was investigated on different
      types of biofunctional surfaces. Patterns of biodomains created by
      microprinting/microspotting of poly-l-lysine or extracellular matrix proteins
      (fibronectin and vitronectin) allowed for non-specific electrostatic or specific,
      receptor mediated interactions, respectively, between stem cells and the surface.
      The neural stem cell line HUCB-NSC has been previously shown to be susceptible to
      MeHgCl in developmentally dependent manner. Here we demonstrated that
      developmental sensitivity of HUCB-NSC to MeHgCl depends upon the type of adhesive
      biomolecules and the geometry of biodomains. Proliferation of HUCB-NSC was
      diminished in time and MeHgCl concentration dependent manner. In addition, the
      response to MeHgCl was found to be cell-type dependent. Undifferentiated cells
      were the most sensitive independently of the type of bioactive domain.
      Significant decrease of GFAP+ cells was detected among cells growing on poly-l
      lysine, while on fibronectin and vitronectin, this effect was observed only in
      the highest (1MUM) concentration of MeHgCl. beta-Tubulin III expressing cells
      were most sensitive on fibronectin domains. In addition, limited bioactive
      domains to MUm in size, as compared to non-patterned larger area of the same
      adhesive substrate, exerted protective role. Thus, the surface area and type of
      cell/biofunctional surface interaction exerted significant influence on
      developmental stage and cell-type specific response of HUCB-NSC to MeHgCl. 

PMID- 23872428
TI  - My Weight Ruler: a simple and effective tool to enhance parental understanding of
      child weight status.
AB  - OBJECTIVE: To compare caregiver identification and understanding of body mass
      index percentile (BMI%) using the CDC Growth Chart and a newly adapted BMI ruler
      ("My Weight Ruler"). METHOD: Between October 2009 and March 2010, eight focus
      groups with 27 low-income, minority caregivers with children 2-4 years of age
      were conducted to choose a meaningful tool to explain child weight status. A
      within-subject experiment comparing identification and interpretation of 2 BMI%
      plots (50th and 97th%) using the CDC Growth Chart and the selected tool was
      performed in February 2012 with 251 primary caregivers of children 2-4 years in a
      primary care clinic. RESULTS: Caregivers chose the "BMI Ruler" a tool used in
      Arkansas, recommended culturally-responsive descriptors of weight status and
      renamed it "My Weight Ruler". 92% of caregivers reported having previously been
      explained the CDC Growth Chart; 37% correctly identified both plots. In contrast,
      92% of caregivers correctly identified both plots on the My Weight Ruler and many
      interpreted the 97th% plot as a health risk and need to change behavior.
      CONCLUSION: My Weight Ruler is a simple, easily understood tool of weight status
      for low-income, minority primary caregivers and could enhance parental knowledge
      and understanding of child weight status.

PMID- 23872427
TI  - Analysis of an expressed sequence tag library from Dicrocoelium dentriticum.
AB  - Dicrocoeliosis caused by Dicrocoelium dendriticum is an important liver disease,
      which affects ruminants all around the world. Despite the significant economic
      losses caused by this trematode, molecular knowledge is very scarce. In fact,
      there is no information in the expressed sequence tag (EST) database about the
      parasite. Furthermore, the immunological diagnosis of dicrocoeliosis remains
      unsatisfactory, and there aren't available recombinant proteins that could be
      tested in the diagnosis. For this reason a cDNA library was constructed with mRNA
      extracted from D. dendriticum adults for first time. A random preliminary
      screening of 230 phage plaques from the library resulted in the identification of
      173 new EST. The deduced proteins expressed by these genes have been described as
      possible vaccine targets in other trematodes, and/or as relevant diagnosis
      antigens. Then, our goal was to identify D. dentriticum diagnosis genes to be
      used as recombinant antigens in the specific immunological diagnosis of the
      trematodoses. A D. dendriticum cDNA encoding an 8-kDa recombinant protein has
      been cloned, expressed in Escherichia coli and evaluated in dicrocoeliosis
      diagnosis using both Western Blot and enzyme-linked immunosorbent assay (ELISA).
      The recombinant expression molecule has demonstrated its value as a diagnosis
      antigen of dicrocoeliosis, able to discriminate between positive and controls on
      day 30 post infection. This is the first research conducted for identification
      and characterization of D. dendriticum ESTs, which can serve as a starting point
      for future research on immunodiagnosis and immunoprofilaxis of dicrocoeliosis. 

PMID- 23872429
TI  - Stochastic stability of discrete-time Markovian jump delay neural networks with
      impulses and incomplete information on transition probability.
AB  - The purpose of this letter is to investigate the stochastic stability for a class
      of discrete-time Markovian jump delay neural networks with impulses and
      incomplete information on transition probability. By using Lyapunov functionals,
      some new results are provided. The obtained results show that impulses can
      stochastically stabilize an unstable discrete-time Markovian jump delay neural
      network. The obtained results also show that the stability property of the
      impulse-free neural network can be retained even under certain destabilizing
      impulses. Two examples together with their simulations are also presented to show
      the effectiveness and the advantage of the obtained results. 

PMID- 23872430
TI  - Storing cycles in Hopfield-type networks with pseudoinverse learning rule:
      admissibility and network topology.
AB  - Cyclic patterns of neuronal activity are ubiquitous in animal nervous systems,
      and partially responsible for generating and controlling rhythmic movements such
      as locomotion, respiration, swallowing and so on. Clarifying the role of the
      network connectivities for generating cyclic patterns is fundamental for
      understanding the generation of rhythmic movements. In this paper, the storage of
      binary cycles in Hopfield-type and other neural networks is investigated. We call
      a cycle defined by a binary matrix Sigma admissible if a connectivity matrix
      satisfying the cycle's transition conditions exists, and if so construct it using
      the pseudoinverse learning rule. Our main focus is on the structural features of
      admissible cycles and the topology of the corresponding networks. We show that
      Sigma is admissible if and only if its discrete Fourier transform contains
      exactly r=rank(Sigma) nonzero columns. Based on the decomposition of the rows of
      Sigma into disjoint subsets corresponding to loops, where a loop is defined by
      the set of all cyclic permutations of a row, cycles are classified as simple
      cycles, and separable or inseparable composite cycles. Simple cycles contain rows
      from one loop only, and the network topology is a feedforward chain with feedback
      to one neuron if the loop-vectors in Sigma are cyclic permutations of each other.
      For special cases this topology simplifies to a ring with only one feedback.
      Composite cycles contain rows from at least two disjoint loops, and the neurons
      corresponding to the loop-vectors in Sigma from the same loop are identified with
      a cluster. Networks constructed from separable composite cycles decompose into
      completely isolated clusters. For inseparable composite cycles at least two
      clusters are connected, and the cluster-connectivity is related to the
      intersections of the spaces spanned by the loop-vectors of the clusters.
      Simulations showing successfully retrieved cycles in continuous-time Hopfield
      type networks and in networks of spiking neurons exhibiting up-down states are
      presented. 

PMID- 23872431
TI  - A low temperature-inducible protein AtSRC2 enhances the ROS-producing activity of
      NADPH oxidase AtRbohF.
AB  - Reactive oxygen species (ROS) produced by NADPH oxidases play critical roles in
      plant environmental responses. Arabidopsis thaliana NADPH oxidase AtRbohF
      mediated ROS-production is involved in abiotic stress responses. Because
      overproduction of ROS is highly toxic to cells, the activity of AtRbohF needs to
      be tightly regulated in response to diverse stimuli. The ROS-producing activity
      of AtRbohF is activated by Ca(2+) and protein phosphorylation, but other
      regulatory factors for AtRbohF are mostly unknown. In this study, we screened for
      proteins that interact with the N-terminal cytosolic region of AtRbohF by a yeast
      two-hybrid screen, and isolated AtSRC2, an A. thaliana homolog of SRC2 (soybean
      gene regulated by cold-2). A co-immunoprecipitation assay revealed that AtSRC2
      interacts with the N-terminal region of AtRbohF in plant cells. Intracellular
      localization of GFP-tagged AtSRC2 was partially overlapped with that of GFP
      tagged AtRbohF at the cell periphery. Co-expression of AtSRC2 enhanced the Ca(2+)
      dependent ROS-producing activity of AtRbohF in HEK293T cells, but did not affect
      its phosphorylation-dependent activation. Low-temperature treatment induced
      expression of the AtSRC2 gene in Arabidopsis roots in proportion to levels of ROS
      production that was partially dependent on AtRbohF. Our findings suggest that
      AtSRC2 is a novel activator of Ca(2+)-dependent AtRbohF-mediated ROS production
      and may play a role in cold responses. 

PMID- 23872432
TI  - Phenotypic heterogeneity in the endothelium of the human vortex vein system.
AB  - The vortex vein system is the drainage pathway for the choroidal circulation and
      serves an important function in the effective drainage of the exceptionally high
      blood flow from the choroidal circulation. As there are only 4-6 vortex veins, a
      large volume of blood must be drained from many choroidal veins into each
      individual vortex vein. The vortex vein system must also cope with passing
      through tissues of different rigidity and significant pressure gradient as it
      transverses from the intrao-cular to the extra-ocular compartments. However,
      little is known about how the vortex vein system works under such complex
      situations in both physiological and pathological condition. Endothelial cells
      play a vital role in other vascular systems, but they have not been studied in
      detail in the vortex vein system. The purpose of this study is to characterise
      the intracellular structures and morphology in both the intra-and extra-ocular
      regions of the human vortex vein system. We hypothesise the presence of
      endothelial phenotypic heterogeneity through the vortex vein system. The inferior
      temporal vortex vein system from human donor eyes were obtained and studied
      histologically using confocal microscopy. The f-actin cytoskeleton and nuclei
      were labelled using Alexa Fluor conjugated Phalloidin and YO-PRO-1. Eight regions
      of the vortex vein system were examined with the venous endothelium studied in
      detail with quantitative data obtained for endothelial cell and nuclei size and
      shape. Significant endothelial phenotypic heterogeneity was found throughout the
      vortex vein system with the most obvious differences observed between the ampulla
      and its downstream regions. Variation in the distribution pattern of smooth
      muscle cells, in particular the absence of smooth muscle cells around the
      ampulla, was noted. Our results suggest the presence of significantly different
      haemodynamic forces in different regions of the vortex vein system and indicate
      that the vortex vein system may play important roles in regulation of the
      choroidal circulation. 

PMID- 23872433
TI  - Femoral osteocyte lacunar density, volume and morphology in women across the
      lifespan.
AB  - Osteocytes are believed to be the primary agents of mechanosensing in bone. Due
      to this important role in the structure-function relationship of bone, osteocytes
      and the spaces they occupy (lacunae) are of increasing interest. Changes in
      lacunae with age are of particular interest in women since they are more
      susceptible to bone loss and fragility associated with senescent diseases
      including osteoporosis. This study's purpose was to test whether differences
      exist in lacunar density (lacunae/mm(3) of bone), orientation and morphology in
      the cortex of adult women spanning the human lifespan. Anterior blocks from the
      femoral shaft from 30 women aged 20-86years were imaged by synchrotron-radiation
      micro-CT. No significant relation between lacunar density and age was detected. A
      significant reduction in lacunar volume with age (p<0.001) was observed,
      alongside changes in lacunar morphology. When divided into two groups (<50 and
      >50years) the younger group's lacunae were ~30% larger and were flatter (p<0.001)
      and less equant (spherical) (p<0.001). To our knowledge the observation that
      lacunar volume and morphology change over the human lifespan is novel,
      potentially resulting from preferential surface infilling within the
      extracellular space. The functional impact of this infilling is unclear but such
      a change in scale likely impacts the mechanosensing function of the osteocyte
      network. Limitations in resolution prevented us from assessing if this infilling
      is associated with disruption of the canaliculi. This hypothesis warrants further
      investigation as, if confirmed, it would represent a profound negative impact on
      the osteocyte network and may provide new insights into age-related bone loss. 

PMID- 23872435
TI  - The tracheal mite Locustacarus buchneri in South American native bumble bees
      (Hymenoptera: Apidae).
AB  - As in other regions of the world, bumble bees (Bombus spp.) are important
      pollinators in the neotropics. Despite its relevance, knowledge on their health
      is still limited in the region. While external acari are known to occur in these
      insects, presence of the internal, tracheal mite Locustacarus buchneri is here
      reported for first time. After the examination of 2,508 individuals of eight
      Bombus species from Argentina, two workers of Bombus bellicosus and one of Bombus
      atratus were found parasitized by L. buchneri in localities within San Luis and
      Buenos Aires provinces, respectively. The rare occurrence recorded agrees with
      findings from elsewhere in the world.

PMID- 23872434
TI  - Likelihood-based classification of cryo-EM images using FREALIGN.
AB  - We describe an implementation of maximum likelihood classification for single
      particle electron cryo-microscopy that is based on the FREALIGN software.
      Particle alignment parameters are determined by maximizing a joint likelihood
      that can include hierarchical priors, while classification is performed by
      expectation maximization of a marginal likelihood. We test the FREALIGN
      implementation using a simulated dataset containing computer-generated projection
      images of three different 70S ribosome structures, as well as a publicly
      available dataset of 70S ribosomes. The results show that the mixed strategy of
      the new FREALIGN algorithm yields performance on par with other maximum
      likelihood implementations, while remaining computationally efficient. 

PMID- 23872436
TI  - Immunodiagnosis of alveolar echinococcosis using urine samples.
AB  - Alveolar echinococcosis (AE) is one of the most lethal zoonotic parasitic
      infections. The diagnosis is based on the combination of the abdominal imaging
      including CT, MRI and PET, and serology. To develop a new diagnostic tool for AE
      with urine as samples, mouse-Echinococcus multilocularis (Em) model and then
      human cases were studied. The antibody levels of urine and serum samples from the
      infected mice and AE cases were well correlated with each other. The sensitivity
      and specificity of the method with urine were 91% and 98%, respectively, when
      IgG4 to crude Em was examined. Comparing with serum samples, the collection of
      urine is easier and safer and the urine diagnostic tool makes surveys of this
      silent disease easier. 

PMID- 23872437
TI  - Muscle wasting from kidney failure-a model for catabolic conditions.
AB  - PURPOSE: Muscle atrophy is a frequent complication of chronic kidney disease
      (CKD) and is associated with increased morbidity and mortality. The processes
      causing loss of muscle mass are also present in several catabolic conditions.
      Understanding the pathogenesis of CKD-induced muscle loss could lead to
      therapeutic interventions that prevent muscle wasting in CKD and potentially,
      other catabolic conditions. MAJOR FINDINGS: Insulin or IGF-1 resistance caused by
      CKD, acidosis, inflammation, glucocorticoids or cancer causes defects in insulin
      stimulated intracellular signaling that suppresses IRS-1 activity leading to
      decreased phosphorylation of Akt (p-Akt). A low p-Akt activates caspase-3 which
      provides muscle proteins substrates of the ubiquitin-proteasome system (UPS). A
      low p-Akt also leads to decreased phosphorylation of forkhead transcription
      factors which enter the nucleus to stimulate the expression of atrogin-1/MAFbx
      and MuRF1, E3 ubiquitin ligases that can be associated with proteolysis of muscle
      cells by the UPS. Caspase-3 also stimulates proteasome-dependent proteolysis in
      muscle. SUMMARY: In CKD, diabetes, inflammatory conditions or in response to
      acidosis or excess glucocorticoids, insulin resistance develops, initiating
      reduced IRS-1/PI3K/Akt signaling. In CKD, this reduces p-Akt which stimulates
      muscle proteolysis by activating caspase-3 and the UPS. Second, caspase-3 cleaves
      actomyosin yielding substrates for the UPS and increased proteasome-mediated
      proteolysis. Third, p-Akt down-regulation suppresses myogenesis in CKD. Fourth,
      exercise in CKD stimulates insulin/IGF-1 signaling to reduce muscle atrophy.
      Lastly, there is evidence that microRNAs influence insulin signaling providing a
      potential opportunity to design therapeutic interventions. This article is part
      of a Directed Issue entitled: Molecular basis of muscle wasting.

PMID- 23872438
TI  - DAB389IL-2 suppresses autoimmune inflammation in the CNS and inhibits T cell
      mediated lysis of glial target cells.
AB  - In multiple sclerosis (MS) and its rodent model, experimental autoimmune
      encephalomyelitis (EAE), activated CD4(+) T cells with upregulated IL-2R mediate
      inflammation and demyelination in the central nervous system (CNS). DAB(389)IL-2,
      a chimeric fusion protein of IL-2 and diphtheria toxin, inhibits human and rodent
      IL-2 activated T cells that express the high affinity interleukin-2 receptor. In
      the present study, DAB(389)IL-2 was used to treat rats with EAE. We wanted to
      investigate the possibility that DAB(389)IL-2 could prevent tissue destruction
      within the CNS. We used a suboptimal dose of DAB(389)IL-2 that allowed
      substantial transmigration of inflammatory cells across the blood-brain barrier.
      DAB(389)IL-2 inhibited infiltration of CD4(+), CD8(+), CD25(+) and TCR
      alphabeta(+) associated mononuclear cells and inflammatory macrophages in the
      spinal cord on day 13 post-immunization, at the peak of disease. Gene expression
      study showed that DAB(389)IL-2 treatment suppressed TNF-alpha and IFN-gamma as
      well as IL-10 cytokine gene expression in the spinal cord of rats with EAE on day
      13. DAB(389)IL-2 in vitro treatment suppressed cytotoxicity of MBP-activated T
      cells from rats with EAE against oligodendrocytes in culture by 66%. Astrocytes
      were less targeted by MBP activated T cells in vitro. This study suggests that
      DAB(389)IL-2 directly targets CD4(+) and CD25(+) (IL-2R) T cells and effector T
      cell function and also indirectly suppresses the activation of macrophage
      CD169(+) (ED3(+)) and microglia CD11b/c (OX42(+)) populations in the CNS.

PMID- 23872439
TI  - Valproic acid decreases the proliferation of telencephalic cells in zebrafish
      larvae.
AB  - Valproic acid (VPA) is used as an antiepileptic drug (AED) or mood stabilizer.
      Recent studies have shown that exposure to VPA during embryonic development
      alters neural progenitor cell (NPC) proliferation, and can also lead to
      behavioral impairment in adult animals. The main goal of this investigation was
      to evaluate the effects of treatment with 2 mM VPA for 3h on cell proliferation
      in the telencephalic area of zebrafish larvae of 5 days post-fertilization (dpf)
      using immunohistochemistry (IHC). It was also determined whether VPA exposure
      affects the learning ability and anxiety levels of zebrafish during adulthood
      using bottom-dwelling behavior and passive avoidance tests. Result of the study
      demonstrated that VPA exposure during development transiently decreased neuronal
      cell proliferation without inducing apoptosis. Additionally, quantitative real
      time PCR (qRT-PCR) data indicated that mRNA expression levels of wnt signaling
      pathway-related factors such as beta-catenin, lef1, and gsk3beta were altered in
      the zebrafish treated with VPA. Interestingly, these effects were reversed over
      time after VPA treatment had ceased. Alterations of passive avoidance learning
      and bottom dwelling behavior were not observed during adulthood after
      developmental VPA exposure. These results may be due to the restoration of cell
      proliferation during the recovery period after VPA treatment.

PMID- 23872440
TI  - Closing the back door.

PMID- 23872441
TI  - Characterization of the evolution of the pharmaceutical regulatory environment.
AB  - This paper is part of a research study that is intended to identify
      pharmaceutical quality risks induced by the ongoing transformation in the
      industry. This study establishes the current regulatory context by characterizing
      the development of the pharmaceutical regulatory environment. The regulatory
      environment is one of the most important external factors that affects a
      company's organization, processes, and technological strategy. This is especially
      the case with the pharmaceutical industry, where its products affect the quality
      of life of the consumers. The quantitative analysis of regulatory events since
      1813 and review of the associated literature resulted in identification of six
      factors influencing the regulatory environment, namely public health protection,
      public health promotion, crisis management, harmonization, innovation, and
      modernization. From 1813 to the 1970s the focus of regulators was centered on
      crisis management and public health protection-a basic mission that has remained
      consistent over the years. Since the 1980s a gradual move in the regulatory
      environment towards a greater focus on public health promotion, international
      harmonization, innovation, and agency modernization may be seen. LAY ABSTRACT:
      The pharmaceutical industry is currently going through changes that affect the
      way it performs its research, manufacturing, and regulatory activities. The
      impact of these changes on the approaches to quality risk management requires
      more understanding. The authors are engaged in research to identify elements of
      the changes that influence pharmaceutical quality. As quality requirements are an
      integral part of the pharmaceutical regulations, a comprehensive understanding of
      these regulations is seen as the first step. The results of this study show that
      (i) public health protection, public health promotion, crisis management,
      harmonization, innovation, and modernization are factors that affect regulations
      in the pharmaceutical industry; (ii) the regulators' main mission of public
      health protection has remained a constant feature over the years; and (iii) since
      the 1970s other factors such as public health promotion, international
      harmonization, innovation, and agency modernization are playing more important
      role in regulatory agency thinking and actions.

PMID- 23872442
TI  - Transformation in the pharmaceutical industry--a systematic analysis of
      operational evidence.
AB  - Through systematic collection and trending of pharmaceutical data, operational
      evidence to verify existence of 14 factors affecting the ongoing pharmaceutical
      transformation has been compiled. These 14 factors are termed transformation
      triggers. The theoretical evidence in support of these triggers is carried
      forward from a systematic review of the literature that was conducted previously.
      Trends in operational evidence and the associated theoretical evidence were
      compared to identify areas of similarity and contrast. Areas of strong
      correlation between theoretical evidence and operational evidence included four
      transformation triggers: a fully integrated pharma network, personalized
      medicine, translational research, and pervasive computing. Key areas of contrast
      included three transformation triggers-namely, healthcare management focus,
      adaptive trials, and regulatory enforcement-for which the operational evidence
      was stronger than the theoretical evidence. LAY ABSTRACT: The intent of this
      paper is to provide proof to demonstrate if there is any operational evidence
      that supports the 14 transformation triggers previously identified during the
      theoretical part of this research. The theoretical evidence for these triggers
      was carried forward to this paper for study from an operational perspective. The
      practical evidence established in this paper was compared with the corresponding
      theoretical evidence to identify areas of similarity and difference. This
      resulted in four triggers that had strong relationship between operational and
      theoretical evidence; they are a fully integrated pharma network, personalized
      medicine, translational research, and pervasive computing. The areas of
      difference included three transformation triggers for which the operational
      evidence was stronger than the theoretical evidence. These were healthcare
      management focus, adaptive trials, and regulatory enforcement.

PMID- 23872443
TI  - Novel Mechanism of Glass Delamination in Type 1A Borosilicate Vials Containing
      Frozen Protein Formulations.
AB  - Storing protein formulations in the frozen state typically improves stability
      during long-term storage as a drug substance or as a drug product. The frozen
      state minimizes chemical degradation and physical instability. However, the
      frozen state is not an optimal storage condition for the glass vial itself. A
      significant issue was observed when small, flake-like pieces of glass particles
      (lamellae) appeared in vials containing thawed protein product. The occurrence of
      glass particles during freeze-thaw results in product rejection and potentially,
      adverse events. In recent years, glass flakes due to chemical delamination have
      been observed in parenteral liquid formulations after long-term storage,
      resulting in a number of product recalls. In this study, for the first time,
      glass delamination is reported in pharmaceutical glass vials containing frozen
      protein formulation, caused by a novel mechanism involving thermally-induced
      mechanical stress. In this article, a monoclonal antibody drug product in glass
      vials and the corresponding placebo vials were studied to identify the
      contributing factors from the freeze-thaw process, such as freezing temperature,
      the presence or absence of protein, and other handling conditions. Freezing
      temperature was found to be the most critical factor. Glass lamellae were only
      observed when the products were frozen to -70  degrees C, while freezing only to 
      30  degrees C did not cause any lamellae formation even after multiple freeze
      thaw cycles. Protein concentration and the handling of the vials were also
      identified as contributing factors. A concentration gradient which formed after
      freeze-thaw induced a higher rate of lamellae occurrence in a subsequent freeze
      thaw cycle compared to vials without the concentration gradient. Analyses by
      Fourier transform infrared spectroscopy and scanning electron microscopy/energy
      dispersive spectroscopy confirmed that the flake-like lamellae were thin, flat
      glass particles. Defects corresponding to the glass flakes were observed by
      scanning electron microscopy on the inner surface of the vials that contained
      lamellae. In addition, inductively coupled plasma mass spectrometry testing did
      not show elevated levels of silicon in the drug product solution, suggesting that
      the glass lamellae formed in the frozen vials was a local, event-based phenomenon
      rather than silica dissolution from the product contact surface or glass
      degradation caused by corrosive attack. These findings can be explained by the
      same thermally-induced mechanical stress which caused vial breakage. Frozen
      protein formulations contracted below -30  degrees C, causing an inward glass
      deformation and a subsequent rapid movement of the glass when the frozen plug of
      drug product solution separated from the vial inner surface at approximately -50
      to -60  degrees C. The mechanical stress released during this separation caused
      vial breakage. The incidence of vial breakage increased with more concentrated
      product and higher fill volume-to-vial volume ratios. The same mechanism applies
      to lamellae formation. As the rapid surface separation occurred, small, thin
      pieces of glass were pulled from the glass surface by the frozen plug, and, as a
      result, glass lamellae particles appeared in the drug product solution after
      thawing. LAY ABSTRACT: In recent years, glass flakes have been observed in
      parenteral liquid formulations due to chemical delamination during long-term
      storage, resulting in a number of product recalls. In our study, we discovered a
      novel mechanism of glass delamination in vials containing frozen protein
      formulations. This glass delamination mechanism has never been reported before,
      and we believe this work will benefit the pharmaceutical scientific community,
      especially the biotechnology and parenteral drug industries. Storing protein
      formulations in the frozen state typically improves stability during long-term
      storage as a drug substance or as a drug product. The frozen state minimizes
      chemical degradation and physical instability. However, the frozen state is not
      an optimal storage condition for the glass vial itself. In this study, we
      observed that after thawing, small, flake-like pieces of glass particles (i.e.,
      lamellae) appeared in vials containing frozen protein formulation. To investigate
      the root cause, we performed a series of freeze-thaw experiments and
      characterized the lamellae particles, the vial inner surface, and the elemental
      composition of the solution. The root cause was determined to be mechanical
      stress caused by thermal contraction of frozen protein formulations below -30 
      degrees C. This contraction caused an inward glass deformation on the vial
      sidewall and, subsequently, the glass vial surface abruptly separated from frozen
      protein formulation. Under this mechanical stress, small, thin glass pieces were
      peeled from the vial inner surface by the frozen formulation, causing lamellae
      formation. The experimental design and results leading to the discovery of the
      novel glass delamination mechanism are presented in detail in this article.

PMID- 23872444
TI  - Pharmaceutical development of a parenteral formulation of conivaptan
      hydrochloride.
AB  - Conivaptan hydrochloride injection (Vaprisol(r)) was developed for the treatment
      of hyponatremia. Because the drug is very slightly soluble in water, pH control
      and cosolvency techniques were used to achieve the optimum concentration required
      for clinical trial material. Stability studies on retained samples of the
      clinical trial material for early-phase trials showed white visible particulates
      mainly in the headspace of the glass ampoule long after completion of the trials.
      The mechanism for generation of the particulate matter was formation of freebase
      of conivaptan hydrochloride because of increase in pH. The pH of the formulation
      for late-phase clinical trials, primary stability studies, and commercial
      production was fine-tuned to prevent particulate formation. The formulation
      contains propylene glycol and ethanol. Considering the nature of the cosolvent
      used in the formulation, the amount of di(2-ethylhexyl)phthalate (DEHP) delivered
      from an infusion system was evaluated, and we confirmed that the level of DEHP
      was lesser than that mentioned in the guideline. In the course of the scale-up
      studies for commercialization, the formulation failed the filter integrity test
      after the compounding solution was filtered. The dimethylsiloxane extracted from
      the silicon tubing used for solvent transfer coated the filter surface, which
      resulted in suppression of the bubble point value. The formulation and
      manufacturing process enabled conivaptan hydrochloride to be approved and
      launched in the market as a parenteral formulation. LAY ABSTRACT: Formulation
      scientists have recognized a trend that promising new chemical entities in the
      drug discovery phase often do not have ideal physicochemical properties for
      formulation. In particular, poor solubility is one of the challenges for
      development of a parenteral dosage form. Here, we describe the case of such a new
      chemical entity, a very slightly soluble hydrochloric salt, which was handed over
      from a drug discovery research laboratory to a pharmaceutical laboratory. pH
      control and cosolvency techniques were used to achieve the optimum concentration
      required for the product. However, a couple of issues emerged; we performed
      confirmatory studies in the course of development, and the results of these
      studies were used to design the formulation and manufacturing process. Most
      prominent issues were particulate matter formation on the inner surface the
      headspace of the ampoule and failure of the filter integrity test. In addition,
      we discuss the root causes and the mechanisms of the above issues and the
      measures taken to prevent them. A part of them are crucial, and information
      obtained from this study is important for development of new chemical entities as
      injectables in the future.

PMID- 23872445
TI  - A Compilation of Metals and Trace Elements Extracted from Materials Relevant to
      Pharmaceutical Applications such as Packaging Systems and Devices.
AB  - Nearly 100 individual test articles, representative of materials used in
      pharmaceutical applications such as packaging and devices, were extracted under
      exaggerated conditions and the levels of 32 metals and trace elements (Ag, Al,
      As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ge, Li, Mg, Mn, Mo, Na, Ni, P, Pb, S,
      Sb, Se, Si, Sn, Sr, Ti, V, Zn, and Zr) were measured in the extracts. The
      extracting solvents included aqueous mixtures at low and high pH and an organic
      solvent mixture (40/60 ethanol water). The sealed vessel extractions were
      performed by placing an appropriate portion of the test articles and an
      appropriate volume of extracting solution in inert extraction vessels and
      exposing the extraction units (and associated extraction blanks) to defined
      conditions of temperature and duration. The levels of extracted target elements
      were measured by inductively coupled plasma atomic emission spectroscopy. The
      overall reporting threshold for most of the targeted elements was 0.05 MUg/mL,
      which corresponds to 0.5 MUg/g for the most commonly utilized extraction
      stoichiometry (1 g of material per 10 mL of extracting solvent). The targeted
      elements could be classified into four major groups depending on the frequency
      with which they were present in the over 250 extractions reported in this study.
      Thirteen elements (Ag, As, Be, Cd, Co, Ge, Li, Mo, Ni, Sn, Ti, V, and Zr) were
      not extracted in reportable quantities from any of the test articles under any of
      the extraction conditions. Eight additional elements (Bi, Cr, Cu, Mn, Pb, Sb, Se,
      and Sr) were rarely extracted from the test articles at reportable levels, and
      three other elements (Ba, Fe, and P) were infrequently extracted from the test
      articles at reportable levels. The remaining eight elements (Al, B, Ca, Mg, Na,
      S, Si, and Zn) were more frequently present in the extracts in reportable
      quantities. These general trends in accumulation behavior were compared to
      compiled lists of elements of concern as impurities in pharmaceutical products.
      LAY ABSTRACT: Nearly 100 individual test articles, representative of materials
      used in pharmaceutical applications such as packaging and devices, were extracted
      under exaggerated conditions, and the levels of thirty-two metals and trace
      elements (Ag, Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ge, Li, Mg, Mn, Mo,
      Na, Ni, P, Pb, S, Sb, Se, Si, Sn, Sr, Ti, V, Zn, and Zr) were measured in the
      extracts. The targeted elements could be classified into four major groups
      depending on the frequency with which they were present in the extractions
      reported in this study: those elements that were not extracted in reportable
      quantities from any of the test articles under any of the extraction conditions,
      those elements that were rarely extracted from the test articles at reportable
      levels, those elements that were infrequently extracted from the test articles at
      reportable levels, and those elements that were more frequently present in the
      extracts in reportable quantities.

PMID- 23872446
TI  - A preliminary investigation into the ability of three rapid microbiological
      methods to detect microorganisms in hospital intravenous pharmaceuticals.
AB  - This study investigated the capability of three rapid microbiological methods to
      detect microorganisms in aseptically prepared pharmacy preparations at National
      Health Service hospitals in the United Kingdom. BacT/ALERT 3D (bioMerieux),
      AKuScreen (Celsis), and BactiFlow ALS (AES Chemunex) technologies were used to
      detect levels of microorganisms in pharmaceutical products. Four products
      selected to represent the range of pharmaceuticals prepared in National Health
      Service hospital pharmacy departments were spiked with known levels of
      microorganisms. The presence of microorganisms in these products was then
      determined using each of the rapid microbiological methods and compared to the
      number determined by traditional total aerobic microbial count methodology. An
      evaluation of the performance parameters associated with each of the methods,
      including cost analysis, was also undertaken. There was good correlation between
      rapid microbiological methods and total aerobic microbial count for heparin and
      parenteral nutrition products. The rapid microbiological methods had difficulty
      recovering Gram-positive organisms from vancomycin and methotrexate products;
      however, protocol developments demonstrated that this was surmountable. The main
      differences between the rapid microbiological method systems were time-to-result,
      the initial equipment cost, and the skill required to operate the instruments.
      The main finding from this work is that rapid microbiological methods can detect
      microbial contamination of hospital pharmaceutical products in a reduced time
      when compared to traditional microbiological techniques. The instrument
      comparison showed that Celsis AKuScreen provided the most rapid result for
      detecting bacteria; BacT/ALERT was the least expensive instrument and the
      simplest system to use; and BactiFlow ALS was the most expensive and more complex
      to use and gave intermediate time to results. LAY ABSTRACT: Traditional methods
      to assure quality and detect any microbial contaminants in intravenous products
      takes at least 2 weeks to complete. Hospital-prepared intravenous products are
      often high risk and have short shelf lives. This sometimes means that the
      traditional quality microbiological results are only available after the product
      has been administered to the patient. There have been some fatal incidents in
      which contaminated intravenous products have been used. Rapid microbiological
      methods have been used in the food, cosmetic, and pharmaceutical industries;
      however, they have not as yet been used in United Kingdom National Health Service
      pharmacy manufacturing. Rapid microbiological methods are able to detect
      contaminants in shortened periods of time. This study investigates the ability of
      three rapid microbiological methods to detect artificially contaminated, National
      Health Service-prepared intravenous products and compares the results to those
      obtained from traditional total aerobic microbial count methodology. The results
      show that there are differences between the methods; however, generally rapid
      microbiological methods are able to detect contaminants from pharmacy-prepared
      intravenous products quicker than current traditional methods.

PMID- 23872447
TI  - Risk-based Methodology for Validation of Pharmaceutical Batch Processes.
AB  - In January 2011, the U.S. Food and Drug Administration published new process
      validation guidance for pharmaceutical processes. The new guidance debunks the
      long-held industry notion that three consecutive validation batches or runs are
      all that are required to demonstrate that a process is operating in a validated
      state. Instead, the new guidance now emphasizes that the level of monitoring and
      testing performed during process performance qualification (PPQ) studies must be
      sufficient to demonstrate statistical confidence both within and between batches.
      In some cases, three qualification runs may not be enough. Nearly two years after
      the guidance was first published, little has been written defining a statistical
      methodology for determining the number of samples and qualification runs required
      to satisfy Stage 2 requirements of the new guidance. This article proposes using
      a combination of risk assessment, control charting, and capability statistics to
      define the monitoring and testing scheme required to show that a pharmaceutical
      batch process is operating in a validated state. In this methodology, an
      assessment of process risk is performed through application of a process failure
      mode, effects, and criticality analysis (PFMECA). The output of PFMECA is used to
      select appropriate levels of statistical confidence and coverage which, in turn,
      are used in capability calculations to determine when significant Stage 2 (PPQ)
      milestones have been met. The achievement of Stage 2 milestones signals the
      release of batches for commercial distribution and the reduction of monitoring
      and testing to commercial production levels. Individuals, moving range, and
      range/sigma charts are used in conjunction with capability statistics to
      demonstrate that the commercial process is operating in a state of statistical
      control. LAY ABSTRACT: The new process validation guidance published by the U.S.
      Food and Drug Administration in January of 2011 indicates that the number of
      process validation batches or runs required to demonstrate that a pharmaceutical
      process is operating in a validated state should be based on sound statistical
      principles. The old rule of "three consecutive batches and you're done" is no
      longer sufficient. The guidance, however, does not provide any specific
      methodology for determining the number of runs required, and little has been
      published to augment this shortcoming. The paper titled "Risk-based Methodology
      for Validation of Pharmaceutical Batch Processes" describes a statistically sound
      methodology for determining when a statistically valid number of validation runs
      has been acquired based on risk assessment and calculation of process capability.

PMID- 23872448
TI  - A 5 year longitudinal study of water quality for final rinsing in the single
      chamber washer-disinfector with a reverse osmosis plant.
AB  - This report deals with the construction and management of the reverse osmosis
      (RO) water system for final rinsing of surgical instruments in the washer
      disinfector. Numerous operational challenges were encountered in our RO water
      system and these were analyzed utilizing the Ishikawa Fishbone diagram. The aim
      was to find potential problems and promote preventive system management for RO
      water. It was found that the measures that existed were inappropriate for
      preventing contamination in the heat-labile RO water system. The storage tank was
      found to be significantly contaminated and had to be replaced with a new one
      equipped with a sampling port and water drainage system. Additional filters and
      an UV treatment lamp were installed. The whole system disinfection started 1.5
      years later using a peracetic acid-based compound after confirming the material
      compatibility. Operator errors were found when a new water engineer took over the
      duty from his predecessor. It was also found that there were some deficiencies in
      the standard operating procedures (SOPs), and that on-the-job training was not
      enough. The water engineer failed to disinfect the sampling port and water
      drainage system. The RO membrane had been used for 4 years, even though the SOP
      standard specified changing it as every 3 years. Various bacteria, such as Rothia
      mucilaginosa, were cultured from the RO water sampled from the equipment. Because
      Rothia mucilaginosa is a resident in the oral cavity and upper respiratory tract,
      it is believed that the bacteria were introduced into the system by the
      maintenance personnel or working environment. Therefore, the presence of R.
      mucilaginosa implied the failure of sanitary maintenance procedures. This study
      suggests that water systems should be designed based on the plans for profound
      system maintenance. It also suggests that SOP and on-the job training are
      essential to avoid any operator errors. These results must be carefully
      considered when either constructing new RO systems or performing maintenance and
      periodical examination of the equipment. LAY ABSTRACT: Reverse osmosis (RO) water
      is used for final rinsing in our washer-disinfector. The authors used the
      Ishikawa Fishbone diagram to clarify the critical points for optimizing RO water
      quality. There existed no measures to prevent contamination in the heat-labile RO
      water system. The storage tank was significantly contaminated and had to be
      replaced with a new one equipped with a sampling port and water drainage system.
      Additional filters and an UV treatment lamp were installed. The whole system
      disinfection started 1.5 years later using a peracetic acid-based compound after
      confirming the material compatibility. Operator errors occurred when a new water
      engineer took over the duty from his predecessor. There were neither standard
      operating procedures (SOPs) nor on-the-job training. The new water engineer had
      failed to disinfect the sampling port and water drainage system. Rothia
      mucilaginosa was cultured from the RO water. It is a resident in the oral cavity
      and upper respiratory tract. This implied the possible failure of sanitary
      procedures in the system maintenance. The Ishikawa Fishbone diagram was useful
      for this study. It suggests that water systems should be designed with plans for
      system maintenance taken into account. It also suggests that SOP and on-the job
      training are essential in order to avoid operator errors.

PMID- 23872449
TI  - Detection and identification of opportunistic Exophiala species using the rolling
      circle amplification of ribosomal internal transcribed spacers.
AB  - Deep infections by melanized fungi deserve special attention because of a
      potentially fatal, cerebral or disseminated course of disease in otherwise
      healthy patients. Timely diagnostics are a major problem with these infections.
      Rolling circle amplification (RCA) is a sensitive, specific and reproducible
      isothermal DNA amplification technique for rapid molecular identification of
      microorganisms. RCA-based diagnostics are characterized by good reproducibility,
      with few amplification errors compared to PCR. The method is applied here to
      species of Exophiala known to cause systemic infections in humans. The ITS rDNA
      region of five Exophiala species (E. dermatitidis, E. oligosperma, E. spinifera,
      E. xenobiotica, and E. jeanselmei) was sequenced and aligned in view of designing
      specific padlock probes to be used for the detection of single nucleotide
      polymorphisms (SNPs) of the Exophiala species concerned. The assay proved to
      successfully amplify DNA of the target fungi at the level of species; while no
      cross-reactivity was observed. Amplification products were visualized on 1%
      agarose gels to verify the specificity of probe-template binding. Amounts of
      reagents were minimized to avoid the generation of false positive results. The
      sensitivity of RCA may help to improve early diagnostics of these difficult to
      diagnose infections. 

PMID- 23872450
TI  - Non-invasive brain stimulation (rTMS and tDCS) in patients with aphasia: mode of
      action at the cellular level.
AB  - A high proportion of patients who have suffered a stroke also suffer from
      aphasia. Approximately half of those affected will remain in this state despite
      intensive language therapy. Non-invasive brain stimulation allows us to directly
      and focally stimulate areas of the brain. Repetitive transcranial magnetic
      stimulation (rTMS) and transcranial direct current stimulation (tDCS), methods
      used in the treatment of aphasia, are based on an imbalance of mutual
      interhemispheric inhibition. In open and sham-controlled studies, a low
      frequency, 1Hz stimulation of the non-lesioned hemisphere (the homologue of
      Broca's area) for a week or more significantly improved spontaneous speech and
      anomia in patients with non-fluent aphasia. These positive outcomes from rTMS
      stimulation developed slowly, often over months following treatment, and
      persisted. Effects of intermittent theta burst stimulation (iTBS) developed
      faster than the low-frequency stimulation, and high-activity enhancement was
      detected in the left hemisphere after the stimulation of Broca's region. Both
      types of tDCS stimulation resulted in improved comprehension and reduced anomia,
      their primary modes of action are distinct, however, both share a common site of
      action with regard to the balance that occurs between inhibitory and excitatory
      neurotransmitters (synaptic and non-synaptic). Both types of non-invasive
      stimulation prepare the lesioned brain for better outcome. 

PMID- 23872451
TI  - Flattening plasma corticosterone levels increases the prevalence of serotonergic
      dorsal raphe neurons inhibitory responses to nicotine in adrenalectomised rats.
AB  - Major depression is characterized by a diminished activity of the brain
      serotonergic system as well as by the flattening of plasma cortisol levels.
      Nicotine improves mood in patients with major depression and in experimentally
      depressed animals by increasing brain serotonin (5-HT), noradrenaline and
      dopamine levels. The present study was directed to determine if flattening plasma
      glucocorticoid levels changes nicotine's stimulatory effects upon 5-HT DRN
      neurons. The experiments were performed in brain slices obtained from rats
      previously (14 days) adrenalectomised and implanted subcutaneously with one
      pellet containing 75mg of corticosterone (Adx+CSR rats). Whole cell voltage and
      current clamp techniques were used to study the activity of immunocitochemically
      identified 5-HT DRN neurons. Administration of nicotine (1MUM) in sham-operated
      animals produced stimulatory effects in all 5-HT DRN neurons studied. In Adx+CSR
      rats however, nicotine inhibited 75% of 5-HT DRN neurons and increased the
      potassium-dependent inward rectifying current. The inhibitory effect of nicotine
      upon 5-HT DRN neurons was dependent on serotonin release inside the DRN, since it
      was converted into a stimulatory response by the selective antagonist of 5-HT1A
      receptors N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridyl)cyclohexanecarboxamide (WAY100635, 25nM). Adx+CSR rats also presented an
      increased function of 5-HT1A autoreceptors, since, in these rats, serotonin (1
      10MUM) produced a higher increase in the potassium dependent inward rectifying
      current in comparison with sham-operated animals. Serotonin release inside DRN
      was mediated by alpha4beta2 nicotinic acetylcholine receptors since the selective
      antagonist of these receptors dihydro-beta-erytroidine hydrobromide (DHbetaE,
      100nM) blocked the inhibitory effects of nicotine 5-HT DRN neurons. These data
      indicate that, in the experimental model of adrenalectomised rats implanted with
      corticosterone pellets, nicotine increases the function of 5-HT1A receptors of 5
      HT DRN neurons. 

PMID- 23872452
TI  - In silico and in vitro comparative activity of novel experimental derivatives
      against Leishmania major and Leishmania infantum promastigotes.
AB  - This in silico and in vitro comparative study was designed to evaluate the
      effectiveness of some biurets (K1 to K8) and glucantime against Leishmania major
      and Leishmania infantum promastigotes. Overall, eight experimental ligands and
      glucantime were docked using AutoDock 4.3 program into the active sites of
      Leishmania major and Leishmania infantum pteridine reductase 1, which were
      modeled using homology modeling programs. The colorimetric MTT assay was used to
      find L. major and L. infantum promastigotes viability at different concentrations
      of biuret derivatives in a concentration and time-dependent manner and the
      obtained results were expressed as 50% and 90% of inhibitory concentration (IC50
      and IC90). In silico method showed that out of eight experimental ligands, four
      compounds were more active on pteridine reductase 1. K3 was the most active
      against L. major promastigotes with an IC50 of 6.8 MUM and an IC90 of 40.2 MUM,
      whereas for L. infantum promastigotes was K8 with IC50 of 7.8 MUM. The
      phenylethyl derivative (K7) showed less toxicity (IC50s>60 MUM) in both
      Leishmania strains. Glucantime displayed less growth inhibition in concentration
      of about 20 MUM. In silico and especially docking results in a recent study were
      in accordance with the in vitro activity of these compounds in presented study
      and compound K3, K2 and K8 showed reasonable levels of selectivity for the
      Leishmania pteridine reductase 1.

PMID- 23872453
TI  - Phthalocyanines functionalized with 2-methyl-5-nitro-1H-imidazolylethoxy and
      1,4,7-trioxanonyl moieties and the effect of metronidazole substitution on
      photocytotoxicity.
AB  - Four novel magnesium(II) and zinc(II) phthalocyanines bearing 1,4,7-trioxanonyl,
      polyether and/or (2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy, heterocyclic
      substituents at their non-peripheral positions were synthesized and assessed in
      terms of physicochemical and biological properties. Magnesium phthalocyanine
      derivatives bearing polyether substituents (Pc-1), a mixed system of polyether
      and heterocyclic substituents (Pc-3), and four heterocyclic substituents (Pc-4),
      respectively, were synthesized following the Linstead macrocyclization reaction
      procedure. Zinc phthalocyanine (Pc-2) bearing polyether substituents at non
      peripheral positions was synthesized following the procedure in n-pentanol with
      the zinc acetate, and DBU. Novel phthalocyanines were purified by flash column
      chromatography and characterized using NMR, MS, UV-Vis and HPLC. Moreover, two
      precursors in macrocyclization reaction phthalonitriles were characterized using
      X-ray. Photophysical properties of the novel macrocycles were evaluated,
      including UV-Vis spectra analysis and aggregation study. All macrocycles
      subjected to singlet oxygen generation and the oxidation rate constant
      measurements exhibited lower quantum yields of singlet oxygen generation in DMSO
      than in DMF. In addition, the Pc-2 molecule was found to be the most efficient
      singlet oxygen generator from the group of macrocycles studied. The
      photocytotoxicity evaluated on the human oral squamous cell carcinoma cell line,
      HSC-3, for Pc-3 was significantly higher than that for Pc-1, Pc-2, and Pc-4.
      Interestingly, Pc-3 was found to be the most active macrocycle in vitro although
      its ability to generate singlet oxygen was significantly lower than those of Pc-1
      and Pc-2. However, attempts to encapsulate phthalocyanines Pc-1-Pc-3 in liposomal
      membranes were unsuccessful. The phthalocyanine-nitroimidazole conjugate, Pc-4
      was encapsulated in phosphatidylglycerol:phosphatidylcholine unilamellar
      liposomes and subjected to photocytotoxicity study. 

PMID- 23872454
TI  - pH-rate profiles support a general base mechanism for galactokinase (Lactococcus
      lactis).
AB  - Galactokinase (GALK), a member the Leloir pathway for normal galactose
      metabolism, catalyzes the conversion of alpha-d-galactose to galactose-1
      phosphate. For this investigation, we studied the kinetic mechanism and pH
      profiles of the enzyme from Lactococcus lactis. Our results show that the
      mechanism for its reaction is sequential in both directions. Mutant proteins
      D183A and D183N are inactive (< 10000 fold), supporting the role of Asp183 as a
      catalytic base that deprotonates the C-1 hydroxyl group of galactose. The pH-kcat
      profile of the forward reaction has a pKa of 6.9 +/- 0.2 that likely is due to
      Asp183. The pH-k(cat)/K(Gal) profile of the reverse reaction further
      substantiates this role as it is lacking a key pKa required for a direct proton
      transfer mechanism. The R36A and R36N mutant proteins show over 100-fold lower
      activity than that for the wild-type enzyme, thus suggesting that Arg36 lowers
      the pKa of the C-1 hydroxyl to facilitate deprotonation.

PMID- 23872455
TI  - K+ channel modulation causes genioglossus inhibition in REM sleep and is a
      strategy for reactivation.
AB  - Rapid eye movement (REM) sleep is accompanied by periods of upper airway motor
      suppression that cause hypoventilation and obstructive apneas in susceptible
      individuals. A common idea has been that upper airway motor suppression in REM
      sleep is caused by the neurotransmitters glycine and gamma-amino butyric acid
      (GABA) acting at pharyngeal motor pools to inhibit motoneuron activity. Data
      refute this as a workable explanation because blockade of this putative
      glycine/GABAergic mechanism releases pharyngeal motor activity in all states, and
      least of all in REM sleep. Here we summarize a novel motor-inhibitory mechanism
      that suppresses hypoglossal motor activity largely in REM sleep, this being a
      muscarinic receptor mechanism linked to G-protein-coupled inwardly rectifying
      potassium (GIRK) channels. We then outline how this discovery informs efforts to
      pursue therapeutic targets to reactivate hypoglossal motor activity throughout
      sleep via potassium channel modulation. One such target is the inwardly
      rectifying potassium channel Kir2.4 whose expression in the brain is almost
      exclusive to cranial motor nuclei. 

PMID- 23872456
TI  - Disruption of mitochondrial membrane integrity induced by amyloid aggregates
      arising from variants of SOD1.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative
      disorder selectively affecting motor neurons; 90% of the total cases are
      sporadic, but 2% are associated with mutations in the gene coding for copper-zinc
      superoxide dismutase (SOD1). The causes of motor neuron death in ALS are poorly
      understood in general, but for SOD1-linked familial ALS (fALS), aberrant
      oligomerization of SOD1 mutant proteins has been strongly implicated. A growing
      body of evidence suggests that fALS-causing mutations destabilize the native
      structure of SOD1, leading to aberrant protein interactions for aggregation. In
      this work, we show that wild-type human SOD1 and two of its mutants (D101N, G72S)
      form amyloid like fibrils under destabilizing condition (in the presence of KSCN
      0.2 M and DTT 50 mM) at 37  degrees C, pH 7.4. The formation of the aggregates
      was monitored by their ability to enhance the fluorescence of Thioflavin T (ThT)
      and their morphology was assessed by transmission electron microscopy (TEM).
      Furthermore, interaction of SOD1 aggregates with mitochondrial membrane of rat
      brain, as an in vitro biological model, with the aim of gaining an insight into
      possible mechanism of cytotoxicity at the membrane level was verified. Release of
      mitochondrial enzyme, malate dehydrogenase (MDH), upon exposure to SOD1
      aggregates demonstrates that these aggregates could affect membrane permeability.

PMID- 23872457
TI  - Early chest tube removal after video-assisted thoracic surgery lobectomy with
      serous fluid production up to 500 ml/day.
AB  - OBJECTIVES: In fast-track pulmonary resections, we removed chest tubes after
      video-assisted thoracic surgery (VATS) lobectomy with serous fluid production up
      to 500 ml/day. Subsequently, we evaluated the frequency of recurrent pleural
      effusions requiring reintervention. METHODS: Data from 622 consecutive patients
      undergoing VATS lobectomy from January 2009 to December 2011 were registered
      prospectively in an institutional database. Data included age, gender, lobe(s)
      resected, bleeding and duration of surgery. Follow-up was 30 days from discharge.
      All complications requiring pleurocentesis or reinsertion of a chest tube, and
      all readmissions were registered. Twenty-three patients were excluded due to
      missing data, in-hospital mortality and loss to follow-up, leaving 599 for final
      analysis. Our primary outcome was the number of patients requiring reintervention
      due to recurrent pleural effusion. Secondary outcomes included time of chest tube
      removal and time to discharge. The incidence of recurrent pleural effusions
      requiring reintervention was compared between three groups according to the
      postoperative day (POD) of chest tube removal (Day 0-1, 2-3 and >=4,
      respectively) using Fisher's exact test. RESULTS: Pleural effusion after chest
      tube removal required reintervention in 17 patients (2.8%). Of these, 7 needed
      readmission. Median time from surgery to chest tube removal was 2 days, and
      median time from surgery to discharge was 4 days. No statistically significant
      association was found between the incidence of reinterventions due to recurrent
      pleural effusion and the POD of chest tube removal (P=0.50). The median time from
      chest tube removal to discharge was 1 day in all groups. Of the patients who
      needed reintervention, none had complications regarding this, except one who
      developed pneumothorax after pleurocentesis. CONCLUSIONS: Our findings suggest
      that chest tube removal after VATS lobectomy is safe despite volumes of serous
      fluid production up to 500 ml/day. The proportion of patients who developed
      pleural effusion necessitating reintervention was low (2.8%), and a complication
      of the reintervention was seen in only 1 patient.

PMID- 23872458
TI  - Haemodynamic performance of a new pericardial aortic bioprosthesis during
      exercise and recovery: comparison with pulmonary autograft, stentless aortic
      bioprosthesis and healthy control groups.
AB  - OBJECTIVES: Since blood flow impairment by aortic valve prosthesis is
      characteristically dynamic, this dynamic component is best and thoroughly
      appreciated by exercise Doppler echocardiography. We sought to determine the
      haemodynamics of a new pericardial aortic bioprosthesis [TrifectaTM-aortic valve
      bioprosthesis (T-AVB), St Jude Medical, MN, USA] at rest and during exercise and
      a 10-min recovery period in comparison with alternative aortic valve prostheses,
      e.g. Ross operation (RO), stentless aortic valve [Medtronic freestyle-aortic
      valve bioprosthesis (MF-AVB)] and a healthy control group (CO). METHODS:
      Haemodynamics at rest and during supine exercise stress testing and a 10-min
      recovery period were evaluated in 32 patients (mean age: 70.8 +/- 6.7 years) with
      T-AVB (mean follow-up: 5 +/- 2 months), 49 with RO (mean age: 43.5 +/- 13.7
      years), 39 with an MF-AVB (mean age: 64.6 +/- 9.4 years) and 26 healthy patients
      (mean age: 39 +/- 9 years). Measurements included mean outflow tract gradient
      (deltap mean, mmHg), effective orifice area index (EOAI, cm(2)/m(2)) and valvular
      resistance (vR, dyn s cm(-5)). RESULTS: Mean body surface area for T-AVB was 1.93
      +/- 0.24 m(2) (median 1.97 m(2)). Mean deltap mean at rest was 7.2 +/- 3.4 mmHg,
      mean EOAI 0.86 +/- 0.23 cm(2)/m(2) and mean vR 50.7 +/- 23.2 dyn s cm(-5). Supine
      stress testing did increase the mean EOAI to 0.98 +/- 0.27 cm(2)/m(2), the mean
      vR to 62.6 +/- 25.3 dyn s cm(-5) and the mean deltap mean to 10.21 +/- 4.7 mmHg,
      respectively (P < 0.05 for all comparisons). During the post-exercise recovery
      period, deltap mean, EOAI and vR showed a prompt normalization within 5 min of
      cessation of exercise. At all the three measurement points, T-AVB and MF-AVB
      revealed low gradients, satisfactory EOAI and low vR. Compared with the RO and a
      healthy control group, both groups showed significantly inferior performance
      throughout the exercise and post-exercise study protocol (P < 0.05). In
      comparison with T-AVB, patients with an MF-AVB only showed significant inferior
      performance throughout series with respect to a higher vR, indicating a smaller
      increase in the EOAI during exercise. During the 10-min post-exercise period, T
      AVB recovered significantly earlier than MF-AVB. CONCLUSIONS: When comparing two
      different types of aortic valve bioprostheses with a gold standard group (RO) and
      a healthy population, both aortic valve bioprostheses perform inferior but reveal
      promising haemodynamics during exercise. During post-exercise haemodynamic
      recovery, only the T-AVB revealed a nearly physiological recovery pattern
      compared with the RO and a healthy control group.

PMID- 23872459
TI  - Could the proportion of premenopausal females influence risk factor
      identification for acute kidney injury after tricuspid valve surgery?

PMID- 23872460
TI  - Is the branched graft technique better than the en bloc technique for total
      aortic arch replacement?
AB  - OBJECTIVES: Total aortic arch replacement remains a surgical challenge. For the
      reimplantation of the supra-aortic vessels, either the en bloc (island) or
      branched graft technique (BGT) is used. The BGT has been proposed to have several
      advantages over the classical island technique. The purpose of this study was to
      compare the perioperative and mid-term follow-up results of these two methods.
      METHODS: From March 2006 to December 2010, 103 patients (74.8% male, age 59 +/-
      12 years) underwent total aortic arch replacement. In 45.6% of the patients (n =
      47), branched grafts (Group A, 35 males, 58 +/- 13 years) were used, while 54.4%
      of the patients (n = 56) underwent en bloc technique (Group B, 42 males, 60 +/-
      12 years). Concomitant procedures were performed as necessary. Twenty-nine
      (28.2%) patients had an aortic aneurysm [Group A: n = 12 (25.5%), Group B: n = 17
      (30.4%)] and 74 (71.8%) patients had an aortic dissection [Group A: n = 35
      (74.5%), Group B: n = 39 (69.6%)]. Thirty-one (30.1%) of these patients [Group A:
      17 (36.2%), Group B: 14 (25%)] had undergone previous cardiac operations.
      RESULTS: Cardiopulmonary bypass, cross-clamp and circulatory arrest times were
      243 +/- 71, 140 +/- 55 and 53 +/- 28 min in Group A and 249 +/- 76, 147 +/- 54
      and 57 +/- 30 min in Group B, respectively (P = n.s.). The overall 30-day
      mortality was 10.6% in Group A and 16.1% in Group B (P = n.s.). The postoperative
      stroke rate was 4.3% in Group A and 3.8% in Group B, respectively (P = n.s.).
      Rethoracotomy due to bleeding was 27.7% in Group A and 23.2% in Group B (P =
      n.s.). At a mean follow-up of 4.0 years, 61.7% of the patients in Group A were
      alive and 29.8% had undergone operations on the downstream aorta. In Group B,
      60.7% of the patients were alive at a mean follow-up of 4.4 years and 20.0% had
      undergone operations on the downstream aorta. None of the patients in Group B
      developed further pathological changes in the 'island' or the proximal supra
      aortic vessels. CONCLUSIONS: The BGT is not inferior perioperatively or in the
      mid-term follow-up compared with the classical island technique. Thus, this
      technique can be used during total arch replacements in most aortic arch
      pathologies.

PMID- 23872461
TI  - Total aortic arch replacement with the elephant trunk technique: single-centre 30
      year results.
AB  - OBJECTIVES: The combined disease of the aortic arch and the descending aorta
      (aneurysms and dissection) remains a surgical challenge. Various approaches have
      been used to treat this complex pathology. In the two-stage operation, at the
      first-stage operation, the aortic arch is replaced through a median sternotomy.
      Later, at the second-stage operation, the descending thoracic aorta is replaced
      through a lateral thoracotomy. The elephant trunk (ET) technique was introduced
      by H.G. Borst at our centre in March 1982, greatly simplifying the second-phase
      operation. We present our 30-year experience. METHODS: From March 1982 to March
      2012, 179 patients (112 males, age 56.4+/-12.6 years) received an ET procedure
      for the combined disease of the aortic arch and the descending aorta (91
      aneurysms, 88 dissections (47 acute)). Fifty-six of these patients had undergone
      previous cardiac operations. Concomitant procedures were performed if necessary.
      The cerebral protection was done either by deep (till 1999) or moderate
      hypothermic circulatory arrest and selective antegrade cerebral perfusion (SACP,
      after 1999). RESULTS: Cardiopulmonary bypass (CPB) and X-clamp times were 208.5+/
      76.5 min and 123.7+/-54.8 min, respectively. The intraoperative mortality and 30
      day mortality during the first-stage operation were 1.7% (3/179) and 17.3%
      (31/179, 15 with AADA), respectively. Perioperative stroke was 7.9% (n=14/176).
      Postoperative recurrent nerve palsy was present in 18.2% (32/176) and paraplegia
      in 5.6% (10/176). The second-stage completion operation was performed as early as
      possible. Fifty-seven second-stage completion procedures were performed, either
      surgically (n=50) or through interventional techniques (n=7). The intraoperative
      and 30-day mortality after the second-stage completion procedures were 5.2%
      (3/57) and 7.0% (4/57), respectively. The stroke, recurrent nerve palsy and
      paraplegia rates were 0, 0 and 7% (4/54), respectively. CONCLUSIONS: The ET
      technique has greatly facilitated the two-stage approach to the surgical
      treatment of combined diseases of the aortic arch and descending aorta. The
      initial learning curve, acute dissections, re-do and concomitant procedures
      partially explain the higher mortality rate. Despite the development of new
      hybrid techniques, there is still a role for the classical ET in selected
      patients, particularly in the context of proven long-term results and cost
      effectiveness.

PMID- 23872462
TI  - Postoperative pain relief after total hip arthroplasty: a randomized, double
      blind comparison between intrathecal morphine and local infiltration analgesia.
AB  - BACKGROUND: Postoperative pain after total hip arthroplasty (THA) can delay
      mobilization. This was assessed after intrathecal morphine (ITM) compared with
      local infiltration analgesia (LIA) using a non-inferiority design. METHODS:
      Eighty patients were recruited in this randomized, double-blind study. ITM 0.1 mg
      (Group ITM) or periarticular local anaesthetic (ropivacaine 300 mg)+ketorolac 30
      mg+ epinephrine 0.5 mg (total volume 151.5 ml) (Group LIA) were compared. After
      24 h, 22 ml of saline (Group ITM) or ropivacaine (150 mg)+ketorolac (30
      mg)+epinephrine (0.1 mg) (Group LIA) were injected via a catheter. After
      operation, rescue analgesic consumption, pain intensity, and home-readiness were
      measured. RESULTS: Morphine consumption was equivalent, median difference 0 mg
      (95% confidence interval -4 to 4.5) between the groups at 0-24 h. During 24-48 h,
      it was lower in Group LIA (3 mg, 0-60 mg, median, range) compared with Group ITM
      (10 mg, 0-81 mg) (P=0.01). Lower pain scores were recorded at rest at 8 h in
      Group ITM (P<0.01), but in Group LIA on standing and mobilization, at 24-48 h
      (P<0.01). Paracetamol and tramadol consumption was lower in Group LIA (P=0.05 and
      0.05, respectively) as was pruritus, nausea, and vomiting (P<0.05). CONCLUSION:
      Lower pain intensity was recorded early after surgery in ITM group but later,
      analgesic consumption, pain intensity on mobilization, and side-effects were
      lower in patients receiving LIA. LIA is a good alternative to ITM in patients
      undergoing THA.

PMID- 23872463
TI  - Heterogeneity in meta-analyses of treatment of acute postoperative pain: a
      review.
AB  - BACKGROUND: Heterogeneity and its causes must be assessed using meta-analyses
      (meta-analysis). Especially in meta-analysis dealing with treatment of acute
      postoperative pain, the type of surgery is a source of heterogeneity. We aimed to
      assess whether the type of surgery is considered a source of heterogeneity in
      meta-analysis and how it is taken into account in meta-analysis evaluating the
      efficacy of treatment of acute postoperative pain. We further compared meta
      analysis that pooled trials of surgeries with highly heterogeneous postoperative
      pain levels, the heterogeneous group, with meta-analysis that pooled trials
      involving surgeries with homogeneous pain levels, the homogenous group. METHODS:
      The meta-analysis reports available in Issue 3, 2011 of the electronic database
      of the Cochrane library and pooling results of randomized or quasi-randomized
      controlled trials that assessed the efficacy of treatment of acute postoperative
      pain alone were considered. A survey of experts established a rating of the
      postoperative pain levels for the type of surgery. For each meta-analysis, the
      different pain level ratings associated with the trials included in the meta
      analysis were considered and the standard deviation (sd) of these ratings
      calculated. From the distribution of sd values, we defined the heterogeneous and
      homogeneous groups. RESULTS: Sixty-one meta-analyses were included; all assessed
      heterogeneity. Twenty-six meta-analyses considered the type of surgery as a
      subgroup (50% vs 38% in the homogeneous group vs heterogeneous group). Forty-four
      reports discussed the type of surgery as a source of clinical heterogeneity (85%
      vs 62% for the homogeneous vs heterogeneous group). Twenty-nine meta-analyses
      compared 'postoperative pain from dental surgery' to 'other type of surgery'.
      CONCLUSIONS: Meta-analyses evaluating treatment of postoperative pain should
      explore clinical heterogeneity associated with the type of surgery for better
      implications for practice.

PMID- 23872464
TI  - I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a
      randomized, double-blind, placebo-controlled, multicentre trial.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) remain significant clinical
      problems for patients, especially nausea. The D2-antagonist droperidol was
      popular for prophylaxis until safety concerns limited its use. In early testing,
      APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising
      antiemetic efficacy at very low doses. We conducted a randomized, double-blind,
      dose-finding study to investigate APD421 in PONV prophylaxis. METHODS: Adult
      surgical patients with >=2 Apfel risk factors for PONV undergoing surgery
      expected to last >=1 h and receiving standard inhalation anaesthesia were
      randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as
      a single i.v. administration at anaesthesia induction. The primary endpoint was
      PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery.
      RESULTS: Two hundred and fifteen patients received study drug, 92% female and 60%
      with >=3 risk factors. Groups were well balanced for baseline characteristics and
      risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57
      79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421
      (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90%
      CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved
      vomiting, rescue medication use, and nausea rates. The safety profile of APD421
      was similar to that of placebo at all doses, with no significant central nervous
      system (CNS) or cardiac side-effects. CONCLUSIONS: APD421 given i.v. before
      surgery is safe and effective at reducing PONV in moderate/high-risk adult
      surgical patients. The optimal dose tested was 5 mg.

PMID- 23872465
TI  - Genipin-cross-linked poly(L-lysine)-based hydrogels: synthesis, characterization,
      and drug encapsulation.
AB  - Genipin-cross-linked hydrogels composed of biodegradable and pH-sensitive
      cationic poly(L-lysine) (PLL), poly(L-lysine)-block-poly(L-alanine) (PLL-b
      PLAla), and poly(L-lysine)-block-polyglycine (PLL-b-PGly) polypeptides were
      synthesized, characterized, and used as carriers for drug delivery. These
      polypeptide hydrogels can respond to pH-stimulus and their gelling and mechanical
      properties, degradation rate, and drug release behavior can be tuned by varying
      polypeptide composition and cross-linking degree. Comparing with natural
      polymers, the synthetic polypeptides with well-defined chain length and
      composition can warrant the preparation of the hydrogels with tunable properties
      to meet the criteria for specific biomedical applications. These hydrogels
      composed of natural building blocks exhibited good cell compatibility and enzyme
      degradability and can support cell attachment/proliferation. The evaluation of
      these hydrogels for in vitro drug release revealed that the controlled release
      profile was a biphasic pattern with a mild burst release and a moderate release
      rate thereafter, suggesting the drug molecules were encapsulated inside the gel
      matrix. With the versatility of polymer chemistry and conjugation of functional
      moieties, it is expected these hydrogels can be useful for biomedical
      applications such as polymer therapeutics and tissue engineering.

PMID- 23872466
TI  - Molecular methods to investigate adhesion, transmigration, invasion and
      intracellular survival of the foodborne pathogen Campylobacter jejuni.
AB  - Campylobacter jejuni is a spiral-shaped Gram-negative pathogen and major agent of
      gastrointestinal foodborne illness in humans worldwide. This pathogen encodes
      numerous described pathogenicity-associated factors involved in important
      processes including bacterial adhesion to, transmigration across, invasion into
      and intracellular survival within intestinal epithelial cells. This review
      article highlights various molecular techniques applied in the studies of each of
      these individual steps of C. jejuni host cell interactions in vitro including
      gentamicin protection assay, chemotaxis and motility assays, transwell and
      intracellular survival assays, G-Lisa, siRNA knockdown, immunohistochemistry,
      immunofluorescence, electron microscopy and luciferase reporter assays. We
      discuss the strengths and limitations of the methods as well as the different
      cell model systems applied. Future work should employ new technologies including
      modern microscopic, proteomics-based and cell signaling approaches to identify
      and characterise novel virulence mechanisms, which are crucial to provide fresh
      insights into the diversity of strategies employed by this important pathogen to
      cause disease. 

PMID- 23872467
TI  - Networking into neural plasticity: a rising score on the cytokine learning curve.

PMID- 23872468
TI  - Systems diagnostics: anticipating the next generation of diagnostic tests based
      on mechanistic insight into disease.
AB  - Societal demand for faster and more accurate assignment of treatments is based in
      both patient care needs and in health economics. From a patient care standpoint,
      there needs to be a transformation from the empiric method of therapeutic
      decision making to avoid unwanted side effects from inefficacious treatments. For
      health economics, the delay in effective therapy and expenditures for ineffective
      therapies add to the burden of care. To accomplish this transformation, we need
      to modify our current method of classifying disease from a phenotypic description
      to one that incorporates the different molecular drivers that created the
      observed phenotype. To do so, a deeper, systems-based understanding of these
      disease drivers is required, which will yield a new generation of diagnostic
      tests, or systems diagnostics. 

PMID- 23872469
TI  - Rapid and sensitive determination of propofol glucuronide in hair by liquid
      chromatography and tandem mass spectrometry.
AB  - A fast, sensitive and selective liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method for the detection and quantitation of propofol glucuronide in
      human hair has been developed and validated. Propofol glucuronide was extracted
      from 10mg of hair using a simple methanol extraction method, with recovery
      greater than 91% at 3 quality control samples (15, 100, 4000 pg/mg). A reversed
      phase column (C8) was used to analyze and the mobile phase was composed of
      ammonium formate and acetonitrile gradient at a flow rate of 0.2 mL/min. The
      lower limit of quantitation (LLOQ) was 5 pg/mg and the assay was linear to 5000
      pg/mg. The intra- and inter-day precision (% CV, coefficient of variation) ranged
      from 1.26 to 4.50% while the accuracy (% RE, relative error) were -4.24 to 4.4%.
      The matrix effects were monitored at 3 different concentrations and the %CV of
      the results for these concentrations was less than 10.6%. Propofol glucuronide
      was stable during processing and analysis in human hair. The procedure was
      validated and applied to the analysis of hair samples in human subjects
      previously administered in propofol.

PMID- 23872470
TI  - Plasmatic dermatan sulfate and chondroitin sulfate determination in
      mucopolysaccharidoses.
AB  - The evaluation of plasmatic galactosaminoglycans, dermatan sulfate (DS) and
      chondroitin sulfate (CS) can be helpful in the early identification of MPS
      patients, also considering that primary storage of one type of GAG can lead to
      secondary accumulation of other lysosomal substrates. We explore the possibility
      to determine plasmatic DS and CS in numerous healthy pediatric (and sometimes
      adult) subjects depending on age and in patients affected by various forms of
      MPS. A highly sensitive HPLC separation and fluorescence detection was applied
      for plasma/serum DS and CS determination after a specific enzymatic treatment
      able to release their constituent disaccharides. DS and CS content decrease
      significantly with age in controls having high values in the first year (~8
      MUg/mL). A highly significant decrease was observed for 1-5-year-old (~-33%) and
      5-10-year-old (~-65%) healthy subgroups. No further decrease was determined
      showing a stabilization after 5 years of age. MPS I Scheie and Hurler patients
      showed rather similar DS and CS content significantly higher than controls
      matched for age. Similarly, MPS II, III and IV subjects all presented
      significantly higher plasmatic DS and CS content compared to healthy subjects
      matched for age. The same trend was determined for the only patient affected by
      MPS VI. Plasmatic DS and CS analyzed by the present procedure may be a useful
      diagnostic and screening marker for various forms of MPS.

PMID- 23872471
TI  - CpG- and LPS-activated MAPK signaling in in vitro cultured salmon (Salmo salar)
      mononuclear phagocytes.
AB  - The Mitogen-activated protein kinases (MAPK) are involved in transmitting
      intracellular signals downstream of diverse cell surface receptors and mediate
      the response to ligands such as growth factors, hormones and cytokines. In
      addition, MAPK are critically involved in the innate immune response to pathogen
      derived substances, commonly referred to as pathogen-associated molecular
      patterns (PAMPs), such as bacterial lipopolysaccharide (LPS) and bacterial DNA
      rich in CpG dinucleotides. Currently, a great deal of knowledge is available
      about the involvement of MAPK in the innate immune response to PAMPs in mammals;
      however, little is known about the role of the different MAPK classes in the
      immune response to PAMPs in lower vertebrates. In the current study, p38
      phosphorylation was induced by CpG oligonucleotides (ODNs) and LPS in primary
      salmon mononuclear phagocytes. Pre-treatment of the cells with a p38 inhibitor
      (SB203580) blocked the PAMP-induced p38 activity and suppressed the upregulation
      of most of the CpG- and LPS-induced transcripts highlighting the role of this
      kinase in the salmon innate immune response to PAMPs. In contrast to p38, the
      phosphorylation of extracellular signal-regulated kinase (ERK), a MAPK involved
      primarily in response to mitogens, was high in resting cells and, surprisingly,
      incubation with both CpG and control ODNs downregulated the phospho-ERK levels
      independently of p38 activation. The basal phospho-ERK level and the CpG
      inducible p38 phosphorylation were greatly influenced by the length of in vitro
      incubation. The basal phospho-ERK level increased gradually throughout a 5-day
      culture period and was PI3K-dependent as demonstrated by its sensitivity to
      Wortmannin suggesting it is influenced by growth factors. Overall these data
      indicate that both basal and PAMP-induced activity of MAPKs might be greatly
      influenced by the differentiation status of salmon mononuclear phagocytes. 

PMID- 23872472
TI  - Characterization of four Mx isoforms in the European eel, Anguilla anguilla.
AB  - Mx protein is known to play an important role in vertebrate immune response to
      viral infection. In this study, cDNA sequences of four Mx isoforms, designated as
      MxA, B, C and D were characterized in the European eel, Anguilla anguilla. These
      sequences contained an open reading frame of 1899, 1896, 1866, 1779 bp, flanked
      by 95, 53, 138, 69 bp of 5' untranslated region and 389, 241, 136, 124 bp of 3'
      untranslated region, respectively. A phylogenetic tree constructed with Mx
      peptide sequences from vertebrates revealed that MxA, C and D in the European eel
      formed into a clade containing zebrafish MxA and MxB and Mx proteins in other
      teleosts, whereas MxB in the eel was clustered together with zebrafish MxD, MxG
      and MxF. The transcription level of all Mx isoforms increased in a poly I:C dose
      dependent manner in peripheral blood leukocytes of eels, as revealed by real-time
      PCR. A further experiment was conducted to reveal the temporal change in
      expression of these isoforms in various organs/tissues following poly I:C
      stimulation, and significant increase in expression was observed at various
      degrees in different organs or in different sampling occasions within the 12 h
      experimental period. In particular, MxA had the highest level of increase, while
      MxB had the lowest; and three isoforms, MxA, MxB and MxD had the highest increase
      in intestine, while the highest increase of MxC expression was observed in liver.
      These four isoforms of eel Mx are thus expressed differentially, and further work
      is certainly required to clarify the activity of promoter elements and antiviral
      activity of these Mx isoforms.

PMID- 23872473
TI  - Fish cell cultures as in vitro models of inflammatory responses elicited by
      immunostimulants. Expression of regulatory genes of the innate immune response.
AB  - We report the differential expression of various genes related to the regulation
      of the innate immune responses, including pro-inflammatory (IL-1beta1, IL-8, TNF
      alpha1, TNF-alpha2) and immune-suppressing (IL-10) cytokines, interferon-induced
      Mx-1 protein, enzymes regulating nitric oxide (inducible nitric oxide synthase,
      arginase-2) and eicosanoid (COX-2) production, and Toll-like pathogen pattern
      recognition receptors TLR-3, TLR-5 and TLR-9, in two lympho-haematopoietic
      stromal cell lines derived from the spleen (trout splenic stroma, TSS) and the
      pronephros (trout pronephric stroma-2, TPS-2) of rainbow trout (Oncorhynchus
      mykiss), as well as in primary cultures of rainbow trout head kidney macrophages,
      after their exposure to the well-known immunostimulants LPS, levamisole and poly
      I:C. Although there were differences in the responses between the two stromal
      cell lines, using reverse transcription followed by real time polymerase chain
      reaction (RT-qPCR) we demonstrated that exposure to the immunostimulants,
      particularly poly I:C and LPS, resulted in significant changes in the expression
      of the immunoregulatory genes in the two stromal cell lines in many cases their
      responses resembling in fold change magnitudes and in response profiles to those
      observed in the primary macrophage cultures. Exposure to poly I:C and, with lower
      fold change values, to LPS produced upregulation of the pro- (IL-1beta, IL-8, TNF
      alpha) and anti-inflammatory (IL-10) cytokine genes, as well as of the Mx-1 gene.
      Furthermore, the immunostimulation elicited the upregulation of COX-2, iNOS and
      arginase-2 genes in the cell lines. Likewise, the TSS and TPS-2 cell lines
      significantly upregulated the expression of TLR-3, TLR-5 and TLR-9 genes after
      exposure to the immunostimulants, thus explaining the ability of the stromal
      cells to recognise and respond to the immunostimulants. Such results give support
      to an important role of lympho-haematopoietic stromal cells in the development
      and control of pro-inflammatory responses in fish. The upregulation of genes of
      pro-inflammatory cytokines and of mediators of the innate immune responses
      correlates well with the previously demonstrated functional capacities, including
      phagocytosis, microbicidal activity and NO production, exhibited by the TSS and
      TPS-2 stromal cell lines when exposed to the same immunostimulants. On the other
      hand, the expression of immunosuppressing genes (IL-10, COX-2 and arginase-2)
      demonstrate that the lympho-haematopoietic stromal cells are also able to
      contribute to the control of inflammatory responses. This study reinforce the
      possibility of using histotypic cell cultures, as those formed by the TSS and TPS
      2 cell lines, formed by heterogeneous cell populations that partially replicates
      the cell-cell and cell-extracellular matrix interactions, to develop cost
      effective and repetitive in vitro systems for the screening of immunostimulant
      candidates for aquaculture, as they are able to replicate in vitro immune
      regulatory networks occurring in vivo.

PMID- 23872474
TI  - Nuclear factor 45 of half smooth tongue sole Cynoglossus semilaevis: gene
      structure, expression profile, and immunoregulatory property.
AB  - Nuclear factor 45 (NF45) is a component of the protein complex called nuclear
      factor of activated T-cells (NFAT), which in mammals regulates interleukin (IL)-2
      expression. To date very little is known about fish NF45. In this study, we
      identified a NF45 (named CsNF45) from half smooth tongue sole Cynoglossus
      semilaevis and examined its gene organization, expression profile, and regulatory
      function. We found that CsNF45 is composed of 387 residues and shares 90.3%-97.9%
      overall sequence identities with the NF45 of human and teleosts. Genetic analysis
      showed that the genomic sequence of the ORF region of CsNF45 consists of 14 exons
      and 13 introns. Constitutive expression of CsNF45 occurred in multiple tissues
      including gill, muscle, brain, heart, liver, head kidney, spleen, and gut.
      Experimental infection with viral and bacterial pathogens upregulated the
      expression of CsNF45 in head kidney and spleen in a time-dependent manner.
      Transient transfection analysis showed that CsNF45 was localized in the nucleus
      and able to stimulate the activity of mouse IL-2 promoter. These results indicate
      that CsNF45 possesses immunoregulatory property and is possibly involved in host
      immune defense against bacterial and viral infection.

PMID- 23872475
TI  - Marine teleost ortholog of catalase from rock bream (Oplegnathus fasciatus):
      molecular perspectives from genomic organization to enzymatic behavior with
      respect to its potent antioxidant properties.
AB  - Catalases are well known antioxidant enzymes that can mainly dismutate hydrogen
      peroxide into water and oxygen in order to prevent oxidative stress. The complete
      genomic DNA (gDNA) sequence of the catalase gene from rock bream (Oplegnathus
      fasciatus) was identified from our custom-constructed BAC genomic DNA library and
      designated as RbCat. RbCat consists of 13 exons, separated by 12 introns, within
      a 13,722-bp gDNA sequence. The complete cDNA sequence (3303 bp) of RbCat is
      comprised of a 1581-bp coding region, encoding a peptide of 527 amino acids (aa)
      in length, with a predicted molecular mass of 60 kDa and a theoretical
      isoelectric point of 8.34. The anticipated promoter region of RbCat contains
      several transcription factor-binding sites, including sites that bind with immune
      and antioxidant-responsive signaling molecules, suggesting its substantial
      transcriptional regulation. RbCat resembles the typical catalase family
      signature, i.e., it is composed of the catalase proximal active site motif along
      with a catalase proximal heme-ligand signature motif and shares great homology
      with its fish counterparts. According to multiple sequence alignment,
      functionally important amino acids present in RbCat were thoroughly conserved
      among its vertebrate counterparts. Phylogenetic analysis revealed that RbCat
      evolved from a vertebrate origin, and further positioned it in the fish clade.
      Recombinant RbCat had noticeable peroxidase activity against its substrate,
      hydrogen peroxide, in a dose-dependent manner. However, it demonstrated
      substantial peroxidase activity within a broad range of temperatures and pH
      values. Constitutive RbCat mRNA expression of different magnitudes was detected
      in a tissue-specific manner, suggesting its diverse role in physiology with
      respect to the tissue type. Moreover, immune challenge experiments using
      Edwardsiella tarda and rock bream iridovirus (RBIV) as live pathogens and
      polyinosinic:polycytidylic acid and lipopolysaccharide as mitogens revealed that
      the transcription of RbCat can be modulated by immune stimulation. Collectively,
      the results obtained in this study suggest that RbCat can function as a potent
      antioxidant enzyme in rock bream and may play a role in post-immune responses
      with respect to its peroxidase activity. 

PMID- 23872476
TI  - Evidence for a role of CETP in HDL remodeling and cholesterol efflux: role of
      cysteine 13 of CETP.
AB  - Cholesteryl ester transfer protein (CETP), a key regulator of high-density
      lipoprotein (HDL) metabolism, induces HDL remodeling by transferring lipids
      between apolipoprotein B-containing lipoproteins and HDL, and/or by promoting
      lipid transfer between HDL subparticles. In this study, we investigated the
      mechanism as to how CETP induces the generation of lipid-poor particles (pre-beta
      HDL) from HDL, which increases ATP-binding cassette transporter 1-mediated
      cholesterol efflux. This CETP-dependent HDL remodeling is enhanced by the CETP
      modulator dalcetrapib both in plasma and isolated HDL. The interaction of
      dalcetrapib with cysteine 13 of CETP is required, since this effect was abolished
      when using mutant CETP in which cysteine 13 was substituted for a serine residue.
      Other thiol-containing compounds were identified as CETP modulators interacting
      with cysteine 13 of CETP. In order to mimic dalcetrapib-bound CETP, mutant CETP
      proteins were prepared by replacing cysteine 13 with the bulky amino acid
      tyrosine or tryptophan. The resultant mutants showed virtually no CETP-dependent
      lipid transfer activity but demonstrated preserved CETP-dependent pre-beta-HDL
      generation. Overall, these data demonstrate that the two functions of CETP i.e.,
      cholesteryl ester transfer and HDL remodeling can be uncoupled by interaction of
      thiol-containing compounds with cysteine 13 of CETP or by introducing large amino
      acid residues in place of cysteine 13. 

PMID- 23872477
TI  - Cancer cells incorporate and remodel exogenous palmitate into structural and
      oncogenic signaling lipids.
AB  - De novo lipogenesis is considered the primary source of fatty acids for lipid
      synthesis in cancer cells, even in the presence of exogenous fatty acids. Here,
      we have used an isotopic fatty acid labeling strategy coupled with metabolomic
      profiling platforms to comprehensively map palmitic acid incorporation into
      complex lipids in cancer cells. We show that cancer cells and tumors robustly
      incorporate and remodel exogenous palmitate into structural and oncogenic
      glycerophospholipids, sphingolipids, and ether lipids. We also find that fatty
      acid incorporation into oxidative pathways is reduced in aggressive human cancer
      cells, and instead shunted into pathways for generating structural and signaling
      lipids. Our results demonstrate that cancer cells do not solely rely on de novo
      lipogenesis, but also utilize exogenous fatty acids for generating lipids
      required for proliferation and protumorigenic lipid signaling. This article is
      part of a special issue entitled Lipid Metabolism in Cancer. 

PMID- 23872478
TI  - Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic
      differentiation potentials of stem cells from apical papilla.
AB  - Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration,
      but the molecular mechanism underlying directed differentiation remains unclear;
      this has restricted potential MSC applications. The histone demethylase, lysine
      (K)-specific demethylase 2A (KDM2A), is evolutionarily conserved and ubiquitously
      expressed members of the JmjC-domain-containing histone demethylase family. A
      previous study determined that KDM2A can regulate the cell proliferation and
      osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2A is
      involved in the other cell lineages differentiation of MSCs. Here, we show that
      depletion of KDM2A by short hairpin RNAs can enhance adipogenic and chondrogenic
      differentiation potentials in human stem cells from apical papilla (SCAPs). We
      found that the stemness-related genes, SOX2, and the embryonic stem cell master
      transcription factor, NANOG were significantly increased after silence of KDM2A
      in SCAPs. Moreover, we found that knock-down of the KDM2A co-factor, BCOR also up
      regulated the mRNA levels of SOX2 and NANOG. Furthermore, Chromatin
      immunoprecipitation assays demonstrate that silence of KDM2A increased the
      histone H3 Lysine 4 (H3K4) trimethylation in the SOX2 and NANOG locus and
      regulates its expression. In conclusion, our results suggested that depletion of
      KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of
      SCAPs by up-regulated SOX2 and NANOG, BCOR also involved in this regulation as co
      factor, and provided useful information to understand the molecular mechanism
      underlying directed differentiation in MSCs. 

PMID- 23872479
TI  - TRAF3IP2 mediates interleukin-18-induced cardiac fibroblast migration and
      differentiation.
AB  - TRAF3IP2 is a cytoplasmic adapter protein and an upstream regulator of IKK/NF
      kappaB and JNK/AP-1. Here we demonstrate for the first time that the
      proinflammatory cytokine interleukin (IL)-18 induces TRAF3IP2 expression in
      primary cardiac fibroblasts (CF) in a Nox4/hydrogen peroxide-dependent manner.
      Silencing TRAF3IP2 using a phosphorothioated, 2'-O-methyl modified, cholesterol
      tagged TRAF3IP2 siRNA duplex markedly attenuated IL-18-induced NF-kappaB and AP-1
      activation and CF migration. Using co-IP/IB and co-localization experiments, we
      show that Nox4 physically associates with IL-18 receptor proteins, and IL-18
      enhances their binding. Further, IL-18 promotes fibroblast to myofibroblast
      transition, as evidenced by enhanced alpha-smooth muscle actin expression, types
      1 and 3 collagen induction, and soluble collagen secretion, via TRAF3IP2. These
      results indicate that TRAF3IP2 is a critical intermediate in IL-18-induced CF
      migration and differentiation in vitro. TRAF3IP2 could serve as a potential
      therapeutic target in cardiac fibrosis and adverse remodeling in vivo. 

PMID- 23872481
TI  - Fourteen-month-old infants copy an action style accompanied by social-emotional
      cues.
AB  - Human adults exaggerate their actions and facial expressions when interacting
      with infants. These infant-directed modifications highlight certain aspects of
      action sequences and attract infants' attention. This study investigated whether
      social-emotional aspects of infant-directed modifications, such as smiling, eye
      contact, and onomatopoeic vocalization, influence infants' copying of another's
      action, especially action style, during the process of achieving an outcome. In
      Study 1, 14-month-old infants (n = 22) saw an experimenter demonstrate goal
      directed actions in an exaggerated manner. Either the style or the end state of
      the actions was accompanied by social-emotional cues from the experimenter.
      Infants copied the style of the action more often when social-emotional cues
      accompanied the style than when they accompanied the end state. In Study 2, a
      different group of 14-month-old infants (n = 22) watched the same exaggerated
      actions as in Study 1, except that either the style or the end state was
      accompanied by a physical sound instead of social-emotional cues. The infants
      copied the end state consistently more often than the style. Taken together,
      these two studies showed that accompanying social-emotional cues provided by a
      demonstrator, but not accompanying physical sound, increased infants' copying of
      action style. These findings suggest that social-emotional cues facilitate
      efficient social learning through the adult-infant interaction.

PMID- 23872480
TI  - The Rf and Rf-like PPR in higher plants, a fast-evolving subclass of PPR genes.
AB  - In the last years, a number of nuclear genes restoring cytoplasmic male sterility
      (CMS) have been cloned in various crop species. The majority of these genes have
      been shown to encode pentatricopeptide repeat proteins (PPR) that act by
      specifically suppressing the expression of sterility-causing mitochondrial
      transcripts. Functional analysis of these proteins has indicated that the
      inhibitory effects of restoring PPR (Rf-PPR) proteins involve various mechanisms,
      including RNA cleavage, RNA destabilization, or translation inhibition. Cross
      species sequence comparison of PPR protein complements revealed that most plant
      genomes encode 10-30 Rf-like (RFL) proteins sharing high-sequence similarity with
      the identified Rf-PPRs from crops. Evolutionary analyses further showed that they
      constitute a monophyletic group apart in the PPR family, with peculiar evolution
      dynamic and constraints. Here we review recent data on RF-PPRs and present the
      latest discoveries on the RFL family, with prospects on the functionality and
      evolution of this peculiar subclass of PPR. 

PMID- 23872482
TI  - An integrated approach for comparative proteomic analysis of human bile reveals
      overexpressed cancer-associated proteins in malignant biliary stenosis.
AB  - Proteomics is a key tool in the identification of new bile biomarkers for
      differentiating malignant and nonmalignant biliary stenoses. Unfortunately, the
      complexity of bile and the presence of molecules interfering with protein
      analysis represent an obstacle for quantitative proteomic studies in bile
      samples. The simultaneous need to introduce purification steps and minimize the
      use of pre-fractionation methods inevitably leads to protein loss and limited
      quantifications. This dramatically reduces the chance of identifying new
      potential biomarkers. In the present study, we included differential
      centrifugation as a preliminary step in a quantitative proteomic workflow
      involving iTRAQ labeling, peptide fractionation by OFFGEL electrophoresis and LC
      MS/MS, to compare protein expression in bile samples collected from patients with
      malignant or nonmalignant biliary stenoses. A total of 1267 proteins were
      identified, including a set of 322 newly described bile proteins, mainly
      belonging to high-density cellular fractions. The subsequent comparative analysis
      led to a 5-fold increase in the number of quantified proteins over previously
      published studies and highlighted 104 proteins overexpressed in malignant
      samples. Finally, immunoblot verifications performed on a cohort of 8 malignant
      (pancreatic adenocarcinoma, n=4; cholangiocarcinoma, n=4) and 5 nonmalignant
      samples (chronic pancreatitis, n=3; biliary stones, n=2) confirmed the results of
      proteomic analysis for three proteins: olfactomedin-4, syntenin-2 and Ras-related
      C3 botulinum toxin substrate 1. This article is part of a Special Issue entitled:
      Biomarkers: A Proteomic Challenge. 

PMID- 23872483
TI  - The ability of an arginine to tryptophan substitution in Saccharomyces cerevisiae
      tRNA nucleotidyltransferase to alleviate a temperature-sensitive phenotype
      suggests a role for motif C in active site organization.
AB  - We report that the temperature-sensitive (ts) phenotype in Saccharomyces
      cerevisiae associated with a variant tRNA nucleotidyltransferase containing an
      amino acid substitution at position 189 results from a reduced ability to
      incorporate AMP and CMP into tRNAs. We show that this defect can be compensated
      for by a second-site suppressor converting residue arginine 64 to tryptophan. The
      R64W substitution does not alter the structure or thermal stability of the enzyme
      dramatically but restores catalytic activity in vitro and suppresses the ts
      phenotype in vivo. R64 is found in motif A known to be involved in catalysis and
      nucleotide triphosphate binding while E189 lies within motif C previously thought
      only to connect the head and neck domains of the protein. Although mutagenesis
      experiments indicate that residues R64 and E189 do not interact directly, our
      data suggest a critical role for residue E189 in enzyme structure and function.
      Both R64 and E189 may contribute to the organization of the catalytic domain of
      the enzyme. These results, along with overexpression and deletion analyses, show
      that the ts phenotype of cca1-E189F does not arise from thermal instability of
      the variant tRNA nucleotidyltransferase but instead from the inability of a
      partially active enzyme to support growth only at higher temperatures.

PMID- 23872484
TI  - Studies on the expression and processing of human proinsulin derivatives encoded
      by different DNA constructs.
AB  - A synthetic gene encoding human proinsulin, containing Escherichia coli preferred
      codons, with an additional N-terminal methionine, was used for the expression, of
      M-proinsulin and construction of nine derivatives. No improvement in expression
      was noted, relative to that of M-proinsulin, when the 5'- of the gene was
      appended to codons for seven amino acids of a well expressed E. coli protein
      (threonine dehydrogenase), or the constructs contained multiple copies of the
      proinsulin gene. That in the latter constructs only the gene adjacent to the
      prometer sequence is expressed, was shown by a construct containing a proinsulin
      gene followed by that for interferon alpha-2b. With the latter construct, the
      proinsulin was, predominantly, expressed. The availability of data on the
      constructs prompted, subjecting these to analysis by two models designed to
      predict the expression of proteins from the sequences, of putative mRNA, around
      the start of translation but no significant relationship was noted. In all cases
      the proteins were expressed as inclusion bodies, which were refolded to give
      products of desired masses and successfully converted into insulin derivatives.
      Of all the constructs containing a trypsin sensitive site before phenylalanine
      (F), the N-terminal sequence, MKR?F, was most efficiently processed, by a
      cocktail of trypsin and buffalo carboxypeptidase B, to give insulin with the
      removal of the N-terminus linker as well as the C-peptide in a single step,
      without cleaving the trypsin sensitive K(29)T(30) peptide bond. 

PMID- 23872485
TI  - Endoscopic approach to the diagnosis and treatment of pancreatic disease.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine the recent
      developments in the use of endoscopic retrograde cholangio-pancreatography (ERCP)
      and endoscopic ultrasound (EUS) in the management of patients with pancreatic
      biliary disease. RECENT FINDINGS: The use of ERCP to guide selective placement of
      pancreatic sphincterotomes, stone extraction balloons, and stents enables
      clinicians to treat pancreatic sphincteric and ductal disorders. Pancreatic
      stones are a remediable cause of recurrent pancreatitis and small calculi can be
      easily removed. The gold standard for the diagnosis of pancreas divisum remains
      ERCP and sphincterotomy is highly effective in the treatment of relapsing
      pancreatitis. Intraductal papillary mucinous neoplasms are the most common
      pancreatic malignancy and ERCP, as well as EUS can identify and sample the solid
      and cystic lesions. Mural nodules can be detected and sampled effectively by EUS
      fine needle aspiration (FNA). The sensitivity of EUS-FNA for pancreatic
      adenocarcinoma is excellent (more than 85%). Although cyst fluid carcinoembryonic
      antigen is a very good marker for the presence of a mucinous cystic lesion, it is
      not an indicator of malignancy. SUMMARY: In summary, ERCP and EUS are important
      tools for the management of benign and malignant lesions of the pancreas.

PMID- 23872487
TI  - Management of pancreatic cysts: a multidisciplinary approach.
AB  - PURPOSE OF REVIEW: An increasing number of patients are being diagnosed with
      pancreatic cysts. Pancreatic cysts are best evaluated by a team of healthcare
      professionals that includes gastroenterologists, surgeons, radiologists,
      pathologists, oncologists and geneticists. RECENT FINDINGS: The international
      consensus guidelines for the management of intraductal papillary mucinous
      neoplasm (IPMN) and mucinous cystic neoplasm were updated in 2012, incorporating
      research that had been reported over a 5-year span since the publication of the
      previous guidelines. There are significant changes in the new guidelines, which
      include redefining main duct IPMN and removing the recommendation for surgical
      resection based on size alone. In addition, the discovery of molecular markers of
      cyst type promises to revolutionize the way patients are diagnosed and managed.
      SUMMARY: The diagnosis and management of patients with pancreatic cysts have
      progressed significantly in recent years. Large prospective, multicenter trials
      are now needed to validate the new international consensus guidelines and to
      assess the accuracy of new molecular markers.

PMID- 23872486
TI  - Genetics of acute and chronic pancreatitis.
AB  - PURPOSE OF REVIEW: Acute pancreatitis, recurrent acute pancreatitis (RAP) and
      chronic pancreatitis are interrelated and progressive inflammatory disorders of
      the pancreas with highly variable and complex susceptibility, severity and
      outcomes. The role of genetics in acute pancreatitis, RAP and progression to
      chronic pancreatitis within a new framework is needed. RECENT FINDINGS: The first
      genome-wide association study in the pancreas has been published with genome-wide
      significance linked with noncoding variants at the PRSS1-PRSS2 locus on
      chromosome seven and the CLDN2 locus on the X chromosome. A new personalized
      medicine paradigm is being considered to facilitate organization of genetic and
      other susceptibility risk compared with the risk of disease progression or
      resolution and risk of complications. SUMMARY: A new framework for organizing
      multiple, complex data sets is emerging. The role of genetics in the context of
      other variables is important in understanding susceptibility to RAP and in the
      modification of disease severity and progression to chronic pancreatitis.
      Questions of when to order testing, what to order and how to use the data in real
      time remains an area for future research and development.

PMID- 23872488
TI  - A new era: endoscopic tissue transplantation.
AB  - PURPOSE OF REVIEW: To describe basic principles of tissue engineering with
      emphasis on the potential role of gastrointestinal endoscopy in regenerative
      medicine. RECENT FINDINGS: Stricturing associated with endoscopic submucosal
      resection and circumferential endoscopic mucosal resection can be prevented
      through transplantation of autologous epidermal cell sheets or seeded
      decellularized biological scaffolds. Lower esophageal sphincter augmentation
      through injection of muscle-derived cells is a novel potential treatment for
      gastroesophageal reflux disease. Stem cell derived tissue has been used to repair
      injured colon in a mouse model of colitis. A bioengineered internal anal
      sphincter has been successfully implanted in mice and showed preserved
      functionality. SUMMARY: The immediate foreseeable application of tissue
      engineering in gastrointestinal endoscopy is in the field of mucosal repair after
      acute injury. Tissue regeneration can be achieved through expansion of autologous
      somatic cells or by induction of multipotent or pluripotent stem cells. Advances
      in cellular scaffolding have made bioengineering of complex tissues a reality.
      Tissue engineering in endoscopy is also being pioneered by studies looking at
      enteral sphincter augmentation and regeneration. The availability of engineered
      tissue for endoscopic application will increase with advances in cell-culturing
      techniques.

PMID- 23872489
TI  - Is the association between depression and blunted cardiovascular stress reactions
      mediated by perceptions of stress?
AB  - Symptoms of depression are related to blunted cardiovascular reactions to acute
      stress tasks. However, it is unclear what factors might mediate this association
      and whether blunted responses are specific to mental stress tasks or are also
      evident with other forms of stress. The present study assessed cardiovascular
      reactivity to both mental and postural stress and the role of background stress
      exposure and stress perception. Undergraduate students (N=119, 81 females) were
      screened for depressive symptoms using the Beck Depression Inventory. Twenty-six
      participants with probable depression and 26 non-depressed controls underwent
      cardiovascular stress testing. Heart rate (HR), systolic (SBP) and diastolic
      (DBP) blood pressure were measured at rest and in response to a 5min orthostatic
      challenge and an 8min mental arithmetic task. Stress exposure was measured using
      the Undergraduate Stress Questionnaire. Perceptions of general life stress were
      assessed using the Perceived Stress Scale (PSS) and perceptions of the stress
      task impact were measured using Threat Appraisal (TA). Symptoms of depression
      were associated with blunted HR, F(2,98)=5.26, p=.010, eta(2)=.097, and SBP,
      F(2,98)=6.47, p=.008, eta(2)=.117, reactions to the mental stress but not to
      postural challenge. HR reactions were mediated by PSS score, while both PSS score
      and TA emerged independently as mediators of SBP reactions. These results confirm
      a negative relationship between depressive symptoms and cardiovascular reactions
      to acute stress, suggest that this association may be stress task-specific, and
      may be mediated by perceptions of stress. 

PMID- 23872490
TI  - The effect of head and coil modeling for the calculation of induced electric
      field during transcranial magnetic stimulation.
AB  - In the present work we studied some of the features related to transcranial
      magnetic stimulation (TMS) computational modeling. Particularly we investigated
      the impact of head model resolution on the estimated distribution of the induced
      electric field, as well as the role of the stimulating magnetic coil model in
      TMS. Using the impedance method we calculated the induced electric field inside a
      realistic numerical phantom of the human head from a commercially available eight
      shaped coil, which was modeled in two ways. The results showed that finer
      resolution of the model has better performance at tissue interfaces eliminating
      numerical artifacts of local peaks. Furthermore, the geometrical details of a TMS
      coil must be taken into account since the predicted amount of volume of brain
      tissue involved can have great variation. Finally, the secondary magnetic field
      that is generated by the induced eddy currents in the tissues can be neglected. 

PMID- 23872491
TI  - Nuclear imprisonment: viral strategies to arrest host mRNA nuclear export.
AB  - Viruses possess many strategies to impair host cellular responses to infection.
      Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is
      critical for antiviral protein production and control of viral infections.
      Several viruses have evolved sophisticated strategies to inhibit nuclear export
      of host mRNAs, including targeting mRNA export factors and nucleoporins to
      compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here,
      we present a review of research focused on suppression of host mRNA nuclear
      export by viruses, including influenza A virus and vesicular stomatitis virus,
      and the impact of this viral suppression on host antiviral responses. 

PMID- 23872492
TI  - Structural and functional insights into foamy viral integrase.
AB  - Successful integration of retroviral DNA into the host chromosome is an essential
      step for viral replication. The process is mediated by virally encoded integrase
      (IN) and orchestrated by 3'-end processing and the strand transfer reaction. In
      vitro reaction conditions, such as substrate specificity, cofactor usage, and
      cellular binding partners for such reactions by the three distinct domains of
      prototype foamy viral integrase (PFV-IN) have been described well in several
      reports. Recent studies on the three-dimensional structure of the interacting
      complexes between PFV-IN and DNA, cofactors, binding partners, or inhibitors have
      explored the mechanistic details of such interactions and shown its utilization
      as an important target to develop anti-retroviral drugs. The presence of a
      potent, non-transferable nuclear localization signal in the PFV C-terminal domain
      extends its use as a model for investigating cellular trafficking of large
      molecular complexes through the nuclear pore complex and also to identify novel
      cellular targets for such trafficking. This review focuses on recent advancements
      in the structural analysis and in vitro functional aspects of PFV-IN.

PMID- 23872494
TI  - Decoding magnetoencephalographic rhythmic activity using spectrospatial
      information.
AB  - We propose a new data-driven decoding method called Spectral Linear Discriminant
      Analysis (Spectral LDA) for the analysis of magnetoencephalography (MEG). The
      method allows investigation of changes in rhythmic neural activity as a result of
      different stimuli and tasks. The introduced classification model only assumes
      that each "brain state" can be characterized as a combination of neural sources,
      each of which shows rhythmic activity at one or several frequency bands.
      Furthermore, the model allows the oscillation frequencies to be different for
      each such state. We present decoding results from 9 subjects in a four-category
      classification problem defined by an experiment involving randomly alternating
      epochs of auditory, visual and tactile stimuli interspersed with rest periods.
      The performance of Spectral LDA was very competitive compared with four
      alternative classifiers based on different assumptions concerning the
      organization of rhythmic brain activity. In addition, the spectral and spatial
      patterns extracted automatically on the basis of trained classifiers showed that
      Spectral LDA offers a novel and interesting way of analyzing spectrospatial
      oscillatory neural activity across the brain. All the presented classification
      methods and visualization tools are freely available as a Matlab toolbox. 

PMID- 23872493
TI  - Implications of genome wide association studies for addiction: are our a priori
      assumptions all wrong?
AB  - Substantial genetic contributions to addiction vulnerability are supported by
      data from twin studies, linkage studies, candidate gene association studies and,
      more recently, Genome Wide Association Studies (GWAS). Parallel to this work,
      animal studies have attempted to identify the genes that may contribute to
      responses to addictive drugs and addiction liability, initially focusing upon
      genes for the targets of the major drugs of abuse. These studies identified
      genes/proteins that affect responses to drugs of abuse; however, this does not
      necessarily mean that variation in these genes contributes to the genetic
      component of addiction liability. One of the major problems with initial linkage
      and candidate gene studies was an a priori focus on the genes thought to be
      involved in addiction based upon the known contributions of those proteins to
      drug actions, making the identification of novel genes unlikely. The GWAS
      approach is systematic and agnostic to such a priori assumptions. From the
      numerous GWAS now completed several conclusions may be drawn: (1) addiction is
      highly polygenic; each allelic variant contributing in a small, additive fashion
      to addiction vulnerability; (2) unexpected, compared to our a priori assumptions,
      classes of genes are most important in explaining addiction vulnerability; (3)
      although substantial genetic heterogeneity exists, there is substantial
      convergence of GWAS signals on particular genes. This review traces the history
      of this research; from initial transgenic mouse models based upon candidate gene
      and linkage studies, through the progression of GWAS for addiction and nicotine
      cessation, to the current human and transgenic mouse studies post-GWAS. 

PMID- 23872495
TI  - A low-frequency oscillatory neural signal in humans encodes a developing decision
      variable.
AB  - We often make decisions based on sensory evidence that is accumulated over a
      period of time. How the evidence for such decisions is represented in the brain
      and how such a neural representation is used to guide a subsequent action are
      questions of considerable interest to decision sciences. The neural correlates of
      developing perceptual decisions have been thoroughly investigated in the
      oculomotor system of macaques who communicated their decisions using an eye
      movement. It has been found that the evidence informing a decision to make an eye
      movement is in part accumulated within the same oculomotor circuits that signal
      the upcoming eye movement. Recent evidence suggests that the somatomotor system
      may exhibit an analogous property for choices made using a hand movement. To
      investigate this possibility, we engaged humans in a decision task in which they
      integrated discrete quanta of sensory information over a period of time and
      signaled their decision using a hand movement or an eye movement. The discrete
      form of the sensory evidence allowed us to infer the decision variable on which
      subjects base their decision on each trial and to assess the neural processes
      related to each quantum of the incoming decision evidence. We found that a low
      frequency electrophysiological signal recorded over centroparietal regions
      strongly encodes the decision variable inferred in this task, and that it does so
      specifically for hand movement choices. The signal ramps up with a rate that is
      proportional to the decision variable, remains graded by the decision variable
      throughout the delay period, reaches a common peak shortly before a hand
      movement, and falls off shortly after the hand movement. Furthermore, the signal
      encodes the polarity of each evidence quantum, with a short latency, and retains
      the response level over time. Thus, this neural signal shows properties of
      evidence accumulation. These findings suggest that the decision-related effects
      observed in the oculomotor system of the monkey during eye movement choices may
      share the same basic properties with the decision-related effects in the
      somatomotor system of humans during hand movement choices. 

PMID- 23872496
TI  - Principal components of functional connectivity: a new approach to study dynamic
      brain connectivity during rest.
AB  - Functional connectivity (FC) as measured by correlation between fMRI BOLD time
      courses of distinct brain regions has revealed meaningful organization of
      spontaneous fluctuations in the resting brain. However, an increasing amount of
      evidence points to non-stationarity of FC; i.e., FC dynamically changes over time
      reflecting additional and rich information about brain organization, but
      representing new challenges for analysis and interpretation. Here, we propose a
      data-driven approach based on principal component analysis (PCA) to reveal hidden
      patterns of coherent FC dynamics across multiple subjects. We demonstrate the
      feasibility and relevance of this new approach by examining the differences in
      dynamic FC between 13 healthy control subjects and 15 minimally disabled relapse
      remitting multiple sclerosis patients. We estimated whole-brain dynamic FC of
      regionally-averaged BOLD activity using sliding time windows. We then used PCA to
      identify FC patterns, termed "eigenconnectivities", that reflect meaningful
      patterns in FC fluctuations. We then assessed the contributions of these patterns
      to the dynamic FC at any given time point and identified a network of connections
      centered on the default-mode network with altered contribution in patients. Our
      results complement traditional stationary analyses, and reveal novel insights
      into brain connectivity dynamics and their modulation in a neurodegenerative
      disease. 

PMID- 23872497
TI  - Characterization of heterotopic ossification in burn patients.
AB  - Heterotopic ossification (HO) is a clinical condition of ectopic bone formation
      in soft tissue. This clinical entity has been associated with genetic disorders,
      traumatic injuries, and musculoskeletal surgeries. In this regard, functional
      impairments secondary to scar contractures seen in burn injuries may be
      exacerbated with underlying HO. The appropriate prevention or management of this
      complication is crucial to optimize outcome in burn patients. This clinical study
      reviews the incidence of HO in our burned patients, diagnostic methods,
      therapeutic approaches including surgical timing and techniques. 

PMID- 23872498
TI  - Mitochondrial gene polymorphisms that protect mice from colitis.
AB  - BACKGROUND & AIMS: Dysregulated energy homeostasis in the intestinal mucosa
      frequently is observed in patients with ulcerative colitis (UC). Intestinal
      tissues from these patients have reduced activity of the mitochondrial oxidative
      phosphorylation (OXPHOS) complex, so mitochondrial dysfunction could contribute
      to the pathogenesis of UC. However, little is known about the mechanisms by which
      OXPHOS activity could be altered. We used conplastic mice, which have identical
      nuclear but different mitochondrial genomes, to investigate activities of the
      OXPHOS complex. METHODS: Colitis was induced in C57BL/6J wild-type (B6.B6) and 3
      strains of conplastic mice (B6.NZB, B6.NOD, and B6.AKR) by administration of
      dextran sodium sulfate or rectal application of trinitrobenzene sulfonate. Colon
      tissues were collected and analyzed by histopathology, immunohistochemical
      analysis, and immunoblot analysis; we also measured mucosal levels of adenosine
      triphosphate (ATP) and reactive oxygen species, OXPHOS complex activity, and
      epithelial cell proliferation and apoptosis. RESULTS: We identified mice with
      increased mucosal OXPHOS complex activities and levels of ATP. These mice
      developed less-severe colitis after administration of dextran sodium sulfate or
      trinitrobenzene sulfonate than mice with lower mucosal levels of ATP. Colon
      tissues from these mice also had increased enterocyte proliferation and
      transcription factor nuclear factor-kappaB activity, which have been shown to
      protect the mucosal barrier-defects in these processes have been associated with
      inflammatory bowel disease. CONCLUSIONS: Variants in mitochondrial DNA that
      increase mucosal levels of ATP protect mice from colitis. Increasing
      mitochondrial ATP synthesis in intestinal epithelial cells could be a therapeutic
      approach for UC.

PMID- 23872499
TI  - Rome III functional constipation and irritable bowel syndrome with constipation
      are similar disorders within a spectrum of sensitization, regulated by serotonin.
AB  - BACKGROUND & AIMS: Patients with irritable bowel syndrome with constipation (IBS
      C) and patients with functional constipation (FC) have similar symptoms, and
      these disorders overlap in their diagnostic features. Little is known about their
      overlap in physiology or the involvement of serotonin signaling. We investigated
      relationships between platelet-depleted plasma concentrations of serotonin,
      gastrointestinal symptoms, and motor-sensory function in patients with FC or IBS
      C compared with healthy volunteers (controls). METHODS: We measured platelet
      depleted plasma concentrations of serotonin in fasting and fed individuals with
      IBS-C (n = 23; 19-50 years old), FC (n = 11; 25-46 years old), and controls (n =
      23; 20-49 years old) recruited in Manchester, UK. We also quantified abdominal
      and bowel-related symptoms, rectal sensitivity, oro-cecal transit, and colonic
      (whole intestine) transit. RESULTS: Patients with IBS-C or FC had similar
      baseline symptoms, bowel habits, oro-cecal and colonic transit, and fasting
      concentrations of serotonin and response to meal ingestion. Only patients with
      IBS-C had increased symptoms after ingestion of a meal (P < .001)-these patients
      tended to have lower sensory thresholds than patients with FC. Defecation
      frequency in the combined group of patients with IBS-C or FC correlated inversely
      with serotonin concentration (r = -0.4; P = .03). Serotonin concentration also
      correlated with pain threshold (r = 0.4; P = .02) and stool threshold (r = 0.5; P
      = .06), which correlated inversely with defecation frequency (r = -0.3; P = .10).
      CONCLUSIONS: FC and IBS-C, based on Rome III criteria, are not distinct
      disorders, symptomatically or physiologically. Instead, they appear to lie in a
      spectrum of visceral sensitivity modulated by serotonin signaling. Symptom
      response to meal ingestion should be considered in patient classification.

PMID- 23872500
TI  - No difference between high-fructose and high-glucose diets on liver
      triacylglycerol or biochemistry in healthy overweight men.
AB  - BACKGROUND & AIMS: Diets high in fructose have been proposed to contribute to
      nonalcoholic fatty liver disease. We compared the effects of high-fructose and
      matched glucose intake on hepatic triacylglycerol (TAG) concentration and other
      liver parameters. DESIGN: In a double-blind study, we randomly assigned 32
      healthy but centrally overweight men to groups that received either a high
      fructose or high-glucose diet (25% energy). These diets were provided during an
      initial isocaloric period of 2 weeks, followed by a 6-week washout period, and
      then again during a hypercaloric 2-week period. The primary outcome measure was
      hepatic level of TAG, with additional assessments of TAG levels in serum and
      soleus muscle, hepatic levels of adenosine triphosphate, and systemic and hepatic
      insulin resistance. RESULTS: During the isocaloric period of the study, both
      groups had stable body weights and concentrations of TAG in liver, serum, and
      soleus muscle. The high-fructose diet produced an increase of 22 +/- 52 MUmol/L
      in the serum level of uric acid, whereas the high-glucose diet led to a reduction
      of 23 +/- 25 MUmol/L (P < .01). The high-fructose diet also produced an increase
      of 0.8 +/- 0.9 in the homeostasis model assessment of insulin resistance, whereas
      the high-glucose diet produced an increase of only 0.1 +/- 0.7 (P = .03). During
      the hypercaloric period, participants in the high-fructose and high-glucose
      groups had similar increases in weight (1.0 +/- 1.4 vs 0.6 +/- 1.0 kg; P = .29)
      and absolute concentration of TAG in liver (1.70% +/- 2.6% vs 2.05% +/- 2.9%; P =
      .73) and serum (0.36 +/- 0.75 vs 0.33 +/- 0.38 mmol/L; P = .91), and similar
      results in biochemical assays of liver function. Body weight changes were
      associated with changes in liver biochemistry and concentration of TAGs.
      CONCLUSIONS: In the isocaloric period, overweight men who were on a high-fructose
      or a high-glucose diet did not develop any significant changes in hepatic
      concentration of TAGs or serum levels of liver enzymes. However, in the
      hypercaloric period, both high-fructose and high-glucose diets produced
      significant increases in these parameters without any significant difference
      between the 2 groups. This indicates an energy-mediated, rather than a specific
      macronutrient-mediated, effect. Clinical trials.gov no: NCT01050140.

PMID- 23872501
TI  - On the differences in degree of renewal produced by the different renewal
      designs.
AB  - This paper addresses sources contributing to the differences in the degree of
      recovery from extinction observed with different renewal paradigms. In two lick
      suppression experiments with rats, we assessed the role of the associative status
      of the acquisition context in both the weakness of AAC renewal and the sometimes
      observed weaker renewal resulting from an ABC design relative to an ABA design.
      In Experiment 1, we observed that AAC renewal relative to an AAA control group
      was small unless Context A had undergone associative deflation (i.e., extinction
      of Context A). Deflation of Context A not only decreased behavioral control by
      the CS in the AAA condition, but increased it in the AAC condition, thereby
      implicating a comparator process in addition to associative summation between the
      CS and test context. In Experiment 2, an excitatory acquisition context was found
      to enhance the difference between ABC and ABA renewal. Associative deflation of
      the acquisition context decreased ABA renewal more than ABC renewal. Thus, the
      associative value of the acquisition context (A) was more positively related to
      the level of renewal when the target CS (X) was tested in this context than when
      it was tested in a neutral but equally familiar context (C), consistent with the
      frequently observed greater renewal in an ABA condition than an ABC condition
      arising from associative summation of the CS and test context. These findings
      demonstrate that the excitatory status of the acquisition context influences the
      observed degree of renewal. 

PMID- 23872502
TI  - A systematic assessment of delay discounting in relation to cocaine and nicotine
      dependence.
AB  - Delay discounting is a measure of impulsivity describing how a reinforcer loses
      value as the delay to its receipt increases. Greater delay discounting is
      reliably observed among those with different substance use disorders (SUDs)
      compared to the general population. Nevertheless, the relation between delay
      discounting and the type and number of substances used remains unclear. The aim
      of this study was to compare delay discounting across four groups of
      participants: cocaine- and nicotine-dependent participants, cocaine-dependent
      only participants, nicotine-dependent only participants, and non-dependent
      controls. One hundred and seven participants completed a computerized delay
      discounting task for hypothetical monetary values. Data were fit to Mazur's
      hyperbolic equation to derive the discounting rate k. Results showed that delay
      discounting was significantly greater in the cocaine- and nicotine-dependent
      group, compared to the nicotine-dependent only group, compared to control group.
      Delay discounting was also greater in the cocaine-dependent only group relative
      to the nicotine-dependent only and control groups, but no differences were
      observed between the cocaine- and nicotine-dependent group and the cocaine
      dependent only group. This study provides evidence that delay discounting differs
      depending on the type of SUD but not on the number of SUDs. 

PMID- 23872503
TI  - Male-male contests for mates, sexual size dimorphism, and sex ratio in a natural
      population of a solitary parasitoid.
AB  - Understanding how different behavioural and life history traits interact is
      fundamental to developing ethological theory. Here we study the interaction of
      male-male competition for mates and sexual size dimorphism in a solitary wasp,
      with implications for sex allocation. In Hymenoptera, females are normally larger
      than males suggesting that males do not benefit as much as females from larger
      size. However, in our focal species, a solitary Eurytoma wasp, males compete for
      mates by pairwise contests at female emergence sites, suggesting that male size
      may strongly affect fitness. In contests observed in the field, larger males were
      more likely to win fights, and males fighting at female emergence sites were much
      larger than average males. Males showed higher variance in body size than
      females, such that all the smallest individuals were males, a majority of medium
      to-large individuals were female, but the majority of largest individuals were
      male. Our data suggest that sexual size dimorphism in this species has been
      affected by intra-sexual selection for male size, which may have implications for
      sex allocation. 

PMID- 23872504
TI  - Effects of genotoxicity and its consequences at the population level in sexual
      and asexual Artemia assessed by analysis of inter-simple sequence repeats (ISSR).
AB  - There is considerable evidence that genetic damage in organisms occurs in the
      environment as a result of exposure to genotoxins and ionising radiation, but we
      have limited understanding of the extent to which this results in adverse
      consequences at a population level. We used inter-simple sequence repeat (ISSR)
      markers to quantify genotoxic effects of the mutagen ethylmethane sulfonate (EMS)
      on a sexual (Artemia franciscana) and an asexual (Artemia parthenogenetica)
      species of brine shrimp. The method provides information similar to that obtained
      with assessment of RAPD (random amplification of polymorphic DNA) but is more
      robust. Genetic damage was transmitted to the F1 generation in both Artemia
      species, but the sexual species showed a greater degree of recovery, as shown by
      higher values of genomic template stability. There was a strong correlation
      between DNA damage and effects on individual fitness parameters: size, survival,
      reproduction and population growth. These effects persisted into the F2
      generation in A. parthenogenetica, but in the sexual A. franciscana only effects
      on fecundity continued beyond the exposed generation, even though there were
      substantial alterations in ISSR patterns in the F1 generation. Genetic biomarkers
      can thus be indicative of effects at the population level, but sexually
      reproducing species have a considerable assimilative capacity for the effects of
      genotoxins. 

PMID- 23872506
TI  - Psychometric properties of the Persian version of the screen for child anxiety
      related emotional disorders (SCARED).
AB  - The present study examined the psychometric properties of the Persian translation
      of the Screen for Child Anxiety-Related Emotional Disorders-child version (SCARED
      C) in a community sample of 557 children, aged 9-13 years, in the city of
      Isfahan, Iran. In addition to the SCARED-C, all the participants completed the
      Revised Children's Manifest Anxiety Scale (RCMAS) and the Children's Depression
      Inventory (CDI). The SCARED-C demonstrated moderate to high internal consistency
      (alpha=0.59-0.80) and good convergent and divergent validity. The one-factor and
      the five-factor model of the SCARED-C fitted the data moderately. However, the
      five-factor model had a significantly better fit than the one-factor model
      (Deltachi(2)=287.346, df=10, P<.001). These findings showed that SCARED-C can be
      used as a reliable and valid measure of anxiety symptoms among children in Iran. 

PMID- 23872505
TI  - Plasma adiponectin and soluble leptin receptor and risk of colorectal cancer: a
      prospective study.
AB  - Adipokines are adipocyte-secreted hormones that may mediate the etiologic link
      between obesity and colorectal cancer; however, the evidence from large
      prospective studies is limited. We prospectively evaluated the association of
      plasma adiponectin and soluble leptin receptor (sOB-R) with colorectal cancer
      risk within the Nurses' Health Study (1990-2008) and the Health Professionals
      Follow-up Study (1994-2008) among 616 incident colorectal cancer cases and 1,205
      controls selected using risk-set sampling and matched on age and date of blood
      draw. In unconditional logistic regression with adjustment for matching factors
      and multiple risk factors, plasma adiponectin was significantly associated with
      reduced risk of colorectal cancer among men, but not among women. Compared with
      men in the lowest quartile of adiponectin, men in the highest quartile had a
      relative risk (RR) for colorectal cancer of 0.55 [95% confidence interval (CI),
      0.35-0.86; Ptrend = 0.02]. The corresponding RR in women was 0.96 (95% CI, 0.67
      1.39; Ptrend = 0.74). Plasma sOB-R was not associated with overall colorectal
      cancer risk in either men or women. A significant heterogeneity was noted in the
      association between sOB-R and colorectal cancer by subsite in women
      (Pheterogeneity = 0.004); sOB-R was significantly associated with increased risk
      of rectal cancer but not colon cancer. These findings support a role for
      adiponectin in colorectal carcinogenesis in men. Further studies are warranted to
      confirm these associations and elucidate potential underlying mechanisms.

PMID- 23872507
TI  - Genetic and environmental influences on relationship between anxiety sensitivity
      and anxiety subscales in children.
AB  - Anxiety sensitivity, a belief that symptoms of anxiety are harmful, has been
      proposed to influence development of panic disorder. Recent research suggests it
      may be a vulnerability factor for many anxiety subtypes. Moderate genetic
      influences have been implicated for both anxiety sensitivity and anxiety,
      however, little is known about the aetiology of the relationship between these
      traits in children. Self-reports of anxiety sensitivity and anxiety symptoms were
      collected from approximately 300 twin pairs at two time points. Partial
      correlations indicated that anxiety sensitivity at age 8 was broadly associated
      with most anxiety subtypes at age 10 (r=0.11-0.17, p<0.05). The associations were
      largely unidirectional, underpinned by stable genetic influences. Non-shared
      environment had unique influences on variables. Phenotypic results showed that
      anxiety sensitivity is a broad predictor of anxiety symptoms in childhood.
      Genetic results suggest that childhood is a developmental period characterised by
      genetic stability and time-specific environmental influences on anxiety-related
      traits. 

PMID- 23872508
TI  - Role of protein kinase C in ischemic "conditioning": from first evidence to
      current perspectives.
AB  - Since the discovery of ischemic preconditioning (IPC) 26 years ago, numerous
      studies attempted to determine the mechanism of this powerful form of
      cardioprotection. One of the first proposed pathways of IPC suggested that the
      preconditioning stimulus activated phospholipase C via G-protein, and
      diacylglycerol released from phospholipid moieties activated protein kinase C
      (PKC) by translocating it from the cytosol to the sarcolemmal membranes. The
      major protective isoform of PKC was found to be the PKC-?. Despite some
      contradictions and controversies, today even the most skeptical opponents
      acknowledge that PKC plays a significant role in the mechanism of IPC. During
      recent years, both the role and the place of PKC-? in the mechanism of IPC have
      been revised. The current review presents the evolution of the "PKC theory" and
      summarizes the most recent data regarding the role of PKC in IPC. In addition to
      classical IPC, PKC appears to play a role in the mechanisms of newer conditioning
      protocols, that is, remote IPC and ischemic postconditioning. 

PMID- 23872509
TI  - Comparison of on-treatment platelet reactivity between triple antiplatelet
      therapy with cilostazol and standard dual antiplatelet therapy in patients
      undergoing coronary interventions: a meta-analysis.
AB  - BACKGROUND: The recent literature has shown that triple antiplatelet therapy with
      cilostazol in addition to the standard dual antiplatelet therapy with aspirin and
      clopidogrel may reduce platelet reactivity and improve clinical outcomes
      following percutaneous coronary intervention. The purpose of this meta-analysis
      is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet
      therapy in regard to on-treatment platelet reactivity. METHODS: Nine studies (n =
      2179) comparing on-treatment platelet reactivity between dual antiplatelet
      therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients
      undergoing percutaneous coronary intervention were included. Primary end points
      were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end
      points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 umol/L
      and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI)
      were computed and 2-sided alpha error <.05 was considered as a level of
      significance. RESULTS: Compared to dual antiplatelet therapy, triple antiplatelet
      therapy had significantly lower maximum platelet aggregation with ADP 5 umol/L
      (MD: -14.4, CI: -21.6 to -7.2, P < .001) and 20 umol/L (MD: -14.9, CI: -22.9 to 
      6.8, P < .001), significantly lower PRUs (MD: -45, CI: -59.4 to -30.6, P < .001)
      and PRI (MD: -26, CI: -36.8 to -15.2, P < .001), and significantly higher P2Y12%
      inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025). CONCLUSION: Addition of
      cilostazol to conventional dual antiplatelet therapy significantly lowers
      platelet reactivity and may explain a decrease in thromboembolic events following
      coronary intervention; however, additional studies evaluating clinical outcomes
      will be helpful to determine the benefit of triple antiplatelet therapy.

PMID- 23872510
TI  - Transcriptome analysis of salt-stressed Deinococcus radiodurans and
      characterization of salt-sensitive mutants.
AB  - Deinococcus radiodurans is a bacterium best known for its extreme resistance to
      high levels of ionizing radiation. Gene expression profiles of D. radiodurans
      exposed to 0.3 M NaCl revealed that at least 389 genes were induced and 415 were
      repressed by twofold or more. A general down-regulation of the central metabolic
      pathways and a strong decrease of nrd gene expression, which encodes proteins
      necessary for DNA synthesis, likely reflect the growth retardation induced by
      NaCl stress. The expression of rsbRSTX, which encodes sigma B (sigma(B)) activity
      regulators, was also reduced by NaCl stress even though D. radiodurans does not
      have sigma(B). The mutation of rsbX (drB0027) decreased the tolerance of D.
      radiodurans to NaCl, suggesting the possible role of the Rsb module in NaCl
      response. On the other hand, NaCl stress activated genes associated with
      osmoprotectant accumulation: the pstSCAB operon, which encodes a high affinity
      phosphate transporter, and DRA0135 and DR1438, which are components of
      transporters of glycine betaine and trehalose. Survival analysis of mutant
      strains lacking DR0392 (membrane-binding protein) and DR1115 (S-layer protein),
      whose expressions were highly activated by NaCl, showed a reduction in NaCl
      tolerance. In addition, the Deltadr0392 strain showed sensitivity to gamma
      irradiation compared to the wild type. These results suggest that DR0392 plays a
      role in the resistance of D. radiodurans to NaCl and gamma-irradiation. 

PMID- 23872511
TI  - Microbial methanogenesis in subsurface oil and coal.
AB  - It is now clear that active methanogens are present in the deep-subsurface. This
      paper reviews microbial population structures and the biodegradation of organic
      compounds to methane in situ within oil reservoirs and coal deposits. It
      summarizes our current knowledge of methanogenes and methanogenesis, fermenters,
      synthrophs and microbial metabolism of complex organic compounds in these two
      widely occurring organic-rich subsurface environments. This review is not
      intended to be an exhaustive report of microbial diversity. Rather, it
      illustrates the similarities and differences between the two environments with
      specific examples, from the nature of the organic molecules to the methanogenic
      metabolic pathways and the structure of the microbial populations to demonstrate
      that widely diverging microbial populations show surprisingly similar metabolic
      capabilities. 

PMID- 23872512
TI  - The role of alpha2 adrenoceptor in mediating noradrenaline action in the
      ventrolateral orbital cortex on allodynia following spared nerve injury.
AB  - The present study examined the role of alpha2 adrenoceptor in mediating
      noradrenaline action in the ventrolateral orbital cortex (VLO) on allodynia
      induced by spared nerve injury (SNI) in the rat. The mechanical paw withdrawal
      threshold (PWT) was measured using von-Frey filaments. Microinjection of
      noradrenaline (1, 2, 4 MUg in 0.5 MUl) into the VLO, contralateral to the site of
      nerve injury, reduced allodynia; PWT increased in a dose-dependent manner.
      Similar to noradrenaline, microinjection of selective alpha2 adrenoceptor agonist
      clonidine into the same VLO site also reduced allodynia, and was blocked by
      selective alpha2 adrenoceptor antagonist yohimbine. Furthermore, administration
      of gamma-aminobutyric acid A (GABAA) receptor antagonist bicuculline or
      picrotoxin to the VLO significantly enhanced clonidine-induced inhibition of
      allodynia, while GABAA receptor agonist muscimol or THIP (2,5,6,7
      retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride) attenuated clonidine
      induced inhibition. These results suggest that noradrenaline acting in the VLO
      can potentially reduce allodynia induced by SNI, and this effect is mediated by
      alpha2 adrenoceptor. Moreover, GABAergic disinhibition may participate in alpha2
      receptor mediating effects in neuropathic pain in the central nervous system.

PMID- 23872513
TI  - Neuro-muscular function in the wobbler murine model of primary motor
      neuronopathy.
AB  - The wobbler mouse represents a model for neurodegenerative disease affecting
      motor neurons. This study explored the importance of fiber type specific changes
      for the contractile dysfunction of soleus and extensor digitorum longus (EDL)
      muscles from wobbler mice using a specific inhibitor of force generation by the
      type II myosin protein. Generally, wobbler condition was associated with ~50%
      reductions in muscle mass and contractile capacity in both muscles. In soleus, an
      increase in the relative abundance of type I myosin protein was observed. Since,
      however, only ~40% of the fibers containing type I myosin had functional
      innervation whereas almost all fibers containing type II myosin were innervated,
      the shift toward type I myosin was without significance for the in vivo
      contractile phenotype. Soleus muscles from wobbler mice were further
      characterized by a 2-fold increase in the width of the twitches, which was
      associated with a reduction in the excitation frequency necessary to elicit
      tetanic contractions. Since the SR Ca(2+) ATPase in wobbler soleus was reduced
      from 22 +/- 5 to 10 +/- 2 nmol/g muscle tissue (P=0.0006), the increase in twitch
      width was most likely caused by delayed recovery of cytosolic Ca(2+). Such
      changes were not observed in EDL. It is concluded that the shift in myosin
      protein from type II to type I previously reported in both innervated and
      denervated wobbler muscles primarily takes place in the population of denervated
      muscle fibers. Since these muscles do not contribute to force generation, the
      transition is, therefore, of limited relevance for the contractile phenotype of
      the muscles. Instead, the slow contractile phenotype of wobbler soleus muscles
      seemed to be a consequence of reduced SR content of Ca(2+) ATPase.

PMID- 23872514
TI  - Separating the influence of the cortex and foam on the mechanical properties of
      porcupine quills.
AB  - Lightweight thin cylinders filled with a foam have applications as collapsible
      energy absorbers for crashworthy and flotation applications. The local buckling
      compressive strength and Young's modulus are dependent on material and
      geometrical properties. Porcupine quills have a thin cortex filled with closed
      cell foam, and are entirely composed of alpha-keratin. The cortex carries the
      majority of the compressive load, but the foam is able to accommodate and release
      some of the deformation of the cortex during buckling. The presence of the foam
      increases the critical buckling strength, buckling strain and elastic strain
      energy absorption over that of the cortex. Good agreement is found between
      experimental results and modeled predictions. A strain distribution map of the
      foam close to the buckled cortex demonstrates that the deformation of the cells
      plays an important role in accommodating local buckling of the cortex. The robust
      connection between the foam and cortex results in superior crushing properties
      compared to synthetic sandwich structure where the foam normally separates from
      the shell. The foam/cortex construction of the quill can guide future biomimetic
      fabrications of light weight buckle-resistant columns. 

PMID- 23872515
TI  - High concentrations of drug in target tissues following local controlled release
      are utilized for both drug distribution and biologic effect: an example with
      epicardial inotropic drug delivery.
AB  - Local drug delivery preferentially loads target tissues with a concentration
      gradient from the surface or point of release that tapers down to more distant
      sites. Drug that diffuses down this gradient must be in unbound form, but such
      drug can only elicit a biologic effect through receptor interactions. Drug excess
      loads tissues, increasing gradients and driving penetration, but with limited
      added biological response. We examined the hypothesis that local application
      reduces dramatically systemic circulating drug levels but leads to significantly
      higher tissue drug concentration than might be needed with systemic infusion in a
      rat model of local epicardial inotropic therapy. Epinephrine was infused
      systemically or released locally to the anterior wall of the heart using a novel
      polymeric platform that provides steady, sustained release over a range of
      precise doses. Epinephrine tissue concentration, upregulation of cAMP, and global
      left ventricular response were measured at equivalent doses and at doses equally
      effective in raising indices of contractility. The contractile stimulation by
      epinephrine was linked to drug tissue levels and commensurate cAMP upregulation
      for IV systemic infusion, but not with local epicardial delivery. Though cAMP was
      a powerful predictor of contractility with local application, tissue epinephrine
      levels were high and variable--only a small fraction of the deposited epinephrine
      was utilized in second messenger signaling and biologic effect. The remainder of
      deposited drug was likely used in diffusive transport and distribution. Systemic
      side effects were far more profound with IV infusion which, though it increased
      contractility, also induced tachycardia and loss of systemic vascular resistance,
      which were not seen with local application. Local epicardial inotropic delivery
      illustrates then a paradigm of how target tissues differentially handle and
      utilize drug compared to systemic infusion.

PMID- 23872516
TI  - Long-term maintenance immunosuppressive regimen with tacrolimus monotherapy.
AB  - BACKGROUND: The long-term outcome of kidney transplant recipients on monotherapy
      with calcineurin inhibitors has been poorly analyzed. This study aimed to
      describe the long-term outcome of patients on Tac monotherapy (mTac) and to
      compare this regimen to a standard dual therapy with Tac/MMF. MATERIAL AND
      METHODS: This retrospective study included 84 consecutive first kidney recipients
      transplanted between 1998 and 2003 and followed until 2010. Patients were treated
      with mTac after the 6th month of transplantation. Survival and incidence of
      adverse events were analyzed and compared to those of patients treated with
      Tac/MMF as maintenance regimen after the 6th month of transplantation. RESULTS:
      Mean follow-up of the mTac cohort was 8.7 +/- 2.2 years. Overall patient and
      graft survival of the mTac cohort was 91.3% and 86.6%, respectively, at year 8
      posttransplant. Tac monotherapy was started in 93.3% of patients at month 6
      posttransplant and maintained in 50% of the cohort at the end of the follow-up
      period. Incidence of acute rejection (AR) and chronic allograft nephropathy (CAN)
      were 11.9% and 16.6%, respectively. Kaplan-Meyer analysis did not show any
      difference in patient and graft survival between mTac patients and patients under
      Tac/MMF. At year 6, compared to Tac/MMF patients, mTac patients had a
      significantly lower incidence of AR after the 6th month posttransplant and no
      difference in CAN, cancer, NODAT, and cardiovascular events incidence.
      CONCLUSIONS: This work suggests that long-term maintenance immunosuppression with
      mTac is safe in low-immunological risk patients and should be considered for use
      especially in patients with MMF intolerance.

PMID- 23872517
TI  - Functional organization of autonomic neural pathways.
AB  - There is now abundant functional and anatomical evidence that autonomic motor
      pathways represent a highly organized output of the central nervous system.
      Simplistic notions of antagonistic all-or-none activation of sympathetic or
      parasympathetic pathways are clearly wrong. Sympathetic or parasympathetic
      pathways to specific target tissues generally can be activated tonically or
      phasically, depending on current physiological requirements. For example, at
      rest, many sympathetic pathways are tonically active, such as those limiting
      blood flow to the skin, inhibiting gastrointestinal tract motility and secretion,
      or allowing continence in the urinary bladder. Phasic parasympathetic activity
      can be seen in lacrimation, salivation or urination. Activity in autonomic motor
      pathways can be modulated by diverse sensory inputs, including the visual,
      auditory and vestibular systems, in addition to various functional populations of
      visceral afferents. Identifying the central pathways responsible for coordinated
      autonomic activity has made considerable progress, but much more needs to be
      done. 

PMID- 23872518
TI  - Annotating temporal information in clinical narratives.
AB  - Temporal information in clinical narratives plays an important role in patients'
      diagnosis, treatment and prognosis. In order to represent narrative information
      accurately, medical natural language processing (MLP) systems need to correctly
      identify and interpret temporal information. To promote research in this area,
      the Informatics for Integrating Biology and the Bedside (i2b2) project developed
      a temporally annotated corpus of clinical narratives. This corpus contains 310 de
      identified discharge summaries, with annotations of clinical events, temporal
      expressions and temporal relations. This paper describes the process followed for
      the development of this corpus and discusses annotation guideline development,
      annotation methodology, and corpus quality. 

PMID- 23872519
TI  - Simultaneous determination of tectorigenin and its metabolites in rat plasma by
      ultra performance liquid chromatography/quadrupole time-of-flight mass
      spectrometry.
AB  - Tectorigenin is a major isoflavone found in the flowers of Pueraria thomsonii
      Benth. and the rhizomes of Belamcanda chinensis (L.) DC. It possesses
      hepatoprotective, estrogenic, hypoglycemic and anti-inflammatory activities. In
      the present study, the plasma pharmacokinetic profile of tectorigenin in rats was
      evaluated. We developed a selective and accurate U-HPLC/Q-TOFMS method for the
      simultaneous characterization of nine tectorigenin metabolites, and quantitation
      of six major metabolites in rat plasma, including tectorigenin-7-O-glucuronide-4'
      O-sulfate (Te-7G-4'S), tectorigenin-di-O-sulfate (Te-diS), tectorigenin-7-O
      glucuronide (Te-7G), tectorigenin-4'-O-glucuronide (Te-4'G), tectorigenin-7-O
      sulfate (Te-7S) and tectorigenin after oral administration of tectorigenin
      (130mg/kg). The plasma concentrations reached maximal values of 6.20+/
      2.05MUmol/L at 0.96+/-0.68h for Te-7G-4'S, 4.42+/-1.36MUmol/L at 1.92+/-2.15h for
      Te-diS, 33.50+/-4.89MUmol/L at 0.75+/-0.67h for Te-7G, 3.28+/-1.01MUmol/L at
      0.75+/-0.67h for Te-4'G, 12.80+/-2.80MUmol/L at 0.85+/-1.54h for Te-7S, and
      12.0+/-0.63MUmol/L at 0.23+/-0.15h for tectorigenin, respectively. Enterohepatic
      recirculation resulted in double or triple peaks concentration curve/time
      profiles of the metabolites. Since the total plasma concentrations of
      tectorigenin conjugated metabolites were much higher than that of the
      tectorigenin aglycone, an extensive phase II metabolism plays an important role
      in the pharmacokinetics of tectorigenin in vivo. 

PMID- 23872521
TI  - Phylogenetic systematics of the genus Echinococcus (Cestoda: Taeniidae).
AB  - Echinococcosis is a serious helminthic zoonosis in humans, livestock and
      wildlife. The pathogenic organisms are members of the genus Echinococcus
      (Cestoda: Taeniidae). Life cycles of Echinococcus spp. are consistently dependent
      on predator-prey association between two obligate mammalian hosts. Carnivores
      (canids and felids) serve as definitive hosts for adult tapeworms and their
      herbivore prey (ungulates, rodents and lagomorphs) as intermediate hosts for
      metacestode larvae. Humans are involved as an accidental host for metacestode
      infections. The metacestodes develop in various internal organs, particularly in
      liver and lungs. Each metacestode of Echinococcus spp. has an organotropism and a
      characteristic form known as an unilocular (cystic), alveolar or polycystic
      hydatid. Recent molecular phylogenetic studies have demonstrated that the type
      species, Echinococcus granulosus, causing cystic echinococcosis is a cryptic
      species complex. Therefore, the orthodox taxonomy of Echinococcus established
      from morphological criteria has been revised from the standpoint of phylogenetic
      systematics. Nine valid species including newly resurrected taxa are recognised
      as a result of the revision. This review summarises the recent advances in the
      phylogenetic systematics of Echinococcus, together with the historical
      backgrounds and molecular epidemiological aspects of each species. A new
      phylogenetic tree inferred from the mitochondrial genomes of all valid
      Echinococcus spp. is also presented. The taxonomic nomenclature for Echinococcus
      oligarthrus is shown to be incorrect and this name should be replaced with
      Echinococcus oligarthra. 

PMID- 23872520
TI  - Immunisation against a serine protease inhibitor reduces intensity of Plasmodium
      berghei infection in mosquitoes.
AB  - The mosquito innate immune response is able to clear the majority of Plasmodium
      parasites. This immune clearance is controlled by a number of regulatory
      molecules including serine protease inhibitors (serpins). To determine whether
      such molecules could represent a novel target for a malaria transmission-blocking
      vaccine, we vaccinated mice with Anopheles gambiae serpin-2. Antibodies against
      Anopheles gambiae serpin-2 significantly reduced the infection of a heterologous
      Anopheles species (Anopheles stephensi) by Plasmodium berghei, however this
      effect was not observed with Plasmodium falciparum. Therefore, this approach of
      targeting regulatory molecules of the mosquito immune system may represent a
      novel approach to transmission-blocking malaria vaccines. 

PMID- 23872522
TI  - Genomic regions of pufferfishes responsible for host specificity of a monogenean
      parasite, Heterobothrium okamotoi.
AB  - The genetic mechanisms underlying host specificity of parasitic infections are
      largely unknown. After hatching, the larvae of the monogenean parasite,
      Heterobothrium okamotoi, attach to the gill filaments of hosts and the post
      larval worms develop there by consuming nutrients from the host. The
      susceptibility to H. okamotoi infection differs markedly among fish species.
      While this parasite can grow on tiger pufferfish (also called fugu), Takifugu
      rubripes, it appears to be rejected by a close congener, grass pufferfish,
      Takifugu niphobles, after initial attachment to the gills. To determine the
      genetic architecture of the pufferfish responsible for this host specificity, we
      performed genome-wide quantitative trait loci analysis. We raised second
      generation (F2) hybrids of the two pufferfish species and experimentally infected
      them with the monogenean in vivo. To assess possible differences in host
      mechanisms between early and later periods of infection, we sampled fish three h
      and 21days after exposure. Genome scanning of fish from the 3h infection trial
      revealed suggestive quantitative trait loci on linkage groups 2 and 14, which
      affected the number of parasites on the gill. However, analysis of fish 21days
      p.i. detected a significant quantitative trait locus on linkage group 9 and three
      other suggestive quantitative trait loci on linkage groups 7, 18 and 22. These
      results indicated the polygenic nature of the host mechanisms involved in the
      infection/rejection of H. okamotoi. Moreover the analyses suggested that host
      factors may play a more important role during the growth period of the parasite
      than during initial host recognition at the time of attachment. Within the 95%
      confidence interval of the linkage group 9 quantitative trait locus in the fugu
      genome, there were 214 annotated protein-coding genes, including immunity-related
      genes such as Irak4, Muc2 and Muc5ac. 

PMID- 23872523
TI  - Cyst formation and faecal-oral transmission of Dientamoeba fragilis--the missing
      link in the life cycle of an emerging pathogen.
AB  - Dientamoeba fragilis is a protozoan parasite emerging as a cause of diarrhoea and
      "irritable-bowel-like" gastrointestinal disease in humans with a propensity for
      establishing long-term, chronic infections in humans. Although Dientamoeba was
      discovered over a century ago its life cycle and mode of transmission is not
      known. No cyst stage has been described and no animal models are presently
      available for the study of this parasite. Here we describe the establishment of
      an animal model using laboratory rodents, the fulfilling of Koch's postulates,
      and the discovery of a new cyst stage in the life cycle of D. fragilis. Our
      demonstration of long-term parasite carriage by rodents and prolonged shedding of
      cysts, together with elevated levels of calprotectin in the stool, confirms the
      capacity of this organism to cause disease and indicates dientamoebiasis should
      be considered in the differential diagnosis of gastrointestinal diseases such as
      Inflammatory Bowel Syndrome (IBS). Finally, we suggest that the cyst stage
      described here is the vehicle that mediates faecal-oral transmission of D.
      fragilis between hosts. 

PMID- 23872524
TI  - Five-year-olds are willing, but 4-year-olds refuse, to trust informants who offer
      new and unfamiliar labels for parts of the body.
AB  - This study employed the selective trust paradigm to examine how children
      interpret novel labels when compared with labels they already know to be accurate
      or inaccurate within the biological domain. The participants--3-, 4-, and 5-year
      olds (N=144)--were allocated to one of three conditions. In the accurate versus
      inaccurate condition, one informant labeled body parts correctly, whereas the
      other labeled them incorrectly (e.g., calling an eye an "arm"). In the accurate
      versus novel condition, one informant labeled body parts accurately, whereas the
      other provided novel labels (e.g., calling an eye a "roke"). Finally, in the
      inaccurate versus novel condition, one informant labeled body parts incorrectly,
      whereas the other offered novel labels. In subsequent test trials, the two
      informants provided conflicting labels for unfamiliar internal organs. In the
      accurate versus inaccurate condition, children sought and endorsed labels from
      the accurate informant. In the accurate versus novel condition, only 4- and 5
      year-olds preferred the accurate informant, whereas 3-year-olds did not
      selectively prefer either informant. In the inaccurate versus novel condition,
      only 5-year-olds preferred the novel informant, whereas 3- and 4-year-olds did
      not demonstrate a selective preference. Results are supportive of previous
      studies suggesting that 3-year-olds are sensitive to inaccuracy and that 4-year
      olds privilege accuracy. However, 3- and 4-year-olds appear to be unsure as to
      how the novel informant should be construed. In contrast, 5-year-olds appreciate
      that speakers offering new information are more trustworthy than those offering
      inaccurate information, but they are cautious in judging such informants as being
      "better" at providing that information.

PMID- 23872525
TI  - Dissecting children's observational learning of complex actions through selective
      video displays.
AB  - Children can learn how to use complex objects by watching others, yet the
      relative importance of different elements they may observe, such as the
      interactions of the individual parts of the apparatus, a model's movements, and
      desirable outcomes, remains unclear. In total, 140 3-year-olds and 140 5-year
      olds participated in a study where they observed a video showing tools being used
      to extract a reward item from a complex puzzle box. Conditions varied according
      to the elements that could be seen in the video: (a) the whole display, including
      the model's hands, the tools, and the box; (b) the tools and the box but not the
      model's hands; (c) the model's hands and the tools but not the box; (d) only the
      end state with the box opened; and (e) no demonstration. Children's later
      attempts at the task were coded to establish whether they imitated the
      hierarchically organized sequence of the model's actions, the action details,
      and/or the outcome. Children's successful retrieval of the reward from the box
      and the replication of hierarchical sequence information were reduced in all but
      the whole display condition. Only once children had attempted the task and
      witnessed a second demonstration did the display focused on the tools and box
      prove to be better for hierarchical sequence information than the display focused
      on the tools and hands only. 

PMID- 23872526
TI  - An in vivo technique for investigating electrophysiological effects of centrally
      administered drugs on single neurons and network behaviour.
AB  - Single neuronal juxtacellular recording with simultaneous cortical
      electroencephalogram (EEG) in whole-animal preparations in vivo has allowed the
      study of the behaviour of individual neurons in relation to whole brain activity.
      Data on single neuron firing, neural synchrony, network behaviour and their
      responses to pharmacological agents can be obtained with dual recordings.
      However, pharmacological effects on cellular and network activity during paired
      single-unit recordings have not been possible due to the difficulties in
      maintaining recordings of two cells for a prolonged period. Here, we describe a
      method of maintaining stable dual cell juxtacellular recordings from distinct
      brain regions, allowing the assessment of single unit activity before, during and
      after the intracerebroventricular (ICV) injection of drugs. Data collection using
      this technique allows correlation both between the two cells and with whole-brain
      EEG, and their responses to pharmacological interventions. This is particularly
      useful for the investigation of the effects of anti-epileptic drugs on animal
      models of epilepsy, where single unit activity of two cells from distinct regions
      can be correlated with each other and with whole-brain activity during pre-ictal,
      ictal and interictal states. We also describe standardised analytical methods of
      quantifying cell firing patterns, the rhythmicity of individual neurons and the
      synchronicity of firing between two neurons in ictal and interictal periods and
      their responses to drug exposure. 

PMID- 23872527
TI  - High performance collection of cerebrospinal fluid in rats: evaluation of
      erythropoietin penetration after osmotic opening of the blood-brain barrier.
AB  - An important issue to be considered when studying a new drug for treatment of
      central nervous system (CNS) diseases is its ability to cross the blood-brain
      barrier (BBB) and distribute throughout the brain. As cerebrospinal fluid (CSF)
      has demonstrated to be an invaluable reservoir to study CNS availability of
      therapeutic proteins, we have developed an improved method for CSF sampling from
      the cisterna magna of rats. The technique enables the simple and rapid collection
      of adequate quantities (50-75 MUl) of blood-free CSF, rendering a high percentage
      of animal survival (99%) without clinic or neurological consequences. Its success
      in avoiding blood contamination of CSF lays in the use of a mixture of
      lidocaine/ephinephrine topically injected in the rat's suboccipital area and
      neck. Another relevant feature of the methodology is its low cost, since the
      puncture device can be easily assembled with cheap and available materials and,
      more importantly, neither expensive stereotaxic equipment nor frame is required.
      The present method is demonstrated by studying the CSF pharmacokinetics of
      recombinant human erythropoietin (rhEPO), a well-studied therapeutic candidate
      for neurological diseases. Moreover, we applied this technique to evaluate a
      strategy of osmotic disruption of the BBB to achieve a faster delivery of rhEPO
      into the CNS.

PMID- 23872528
TI  - An evaluation of the referral process in the emergency department.
AB  - INTRODUCTION: Making an effective telephone referral is an important skill for an
      emergency department (ED) clinician. It is essential for patient safety that the
      information is conveyed in a succinct manner to the correct inpatient specialty.
      The aim of this study was to assess: the impact of grade of staff making the
      referral; specialty referred to; and condition or patient problem. It also aimed
      to identify current problems or barriers in the referral process. METHODS: This
      prospective study took place in one large teaching hospital in the UK. There were
      two parts: data collection to obtain information on each referral made by ED
      staff; and questionnaires administered to obtain opinions on the current referral
      process from both staff making and receiving the referrals. RESULTS: Data were
      collected over 6 days and included 362 referrals. The mean evaluation of the
      referral process (scored 0-4) for all referrals was 3.34 (SD 0.95). 22 ED staff
      responding (64.7%) felt that some specialties were more difficult to refer to
      than others. 60.6% of non-ED staff accepting referrals felt they would like some
      form of senior ED screening process prior to referral compared with 20.6% of ED
      staff. The most common topics commented on were communication, education and
      process. DISCUSSION: There are differences in understanding and opinion between
      ED and non-ED staff about the referral process. There are also factors which
      influence ease of referral: specialty referring to and patient problem. More
      intervention studies are required to identify solutions that can be implemented
      and sustained in routine practice.

PMID- 23872529
TI  - Analysis of the complete genome of the first Irkut virus isolate from China:
      comparison across the Lyssavirus genus.
AB  - The genome of Irkut virus, isolate IRKV-THChina12, the first non-rabies
      lyssavirus from China (of bat origin), has been completely sequenced. In general,
      coding and non-coding regions of this viral genome are similar to those of other
      lyssaviruses. However, alignment of the deduced amino acid sequences of the
      structural proteins of IRKV-THChina12 with those of other lyssavirus
      representatives revealed significant variability between viral species. The
      nucleoprotein and matrix protein were found to be the most conserved, followed by
      the large protein, glycoprotein and phosphoprotein. Differences in the antigenic
      sites in glycoprotein may result in only partial protection of the available
      rabies biologics against Irkut virus, which is of particular concern for pre- and
      post-exposure rabies prophylaxis. 

PMID- 23872530
TI  - Effects of whole body vibration training on balance in adolescents with and
      without Down syndrome.
AB  - The present study aimed to determine whether a whole body vibration training
      program (WBV) is able to improve static standing balance in adolescents with and
      without Down syndrome (DS). Thirty adolescents with DS aged 11-20 years (DSG) and
      27 adolescent, age/sex matched, without DS (CG) joined the study. Participants of
      each group were divided into two comparable groups, those who performed WVB (in
      DSG: VDSG; in CG: VCG) and those who did not perform WVB (in DSG: nVDSG; in CG:
      nVCG). Static-standing-balance under four conditions (C1: open-eyes/fixed-foot
      support; C2: closed-eyes/fixed-foot-support; C3: open-eyes/compliant-foot
      support; C4: closed-eyes/compliant-foot-support) was examine, before and after a
      20-week WBV training program. For balance study, Postural-Parameters (PPs), based
      on center of pressure (COP) oscillations (anterior/posterior and medial/lateral
      COP excursion and COP mean velocity), and PPs ratios among the four conditions
      were calculated. After WBV training, no significant differences were found in any
      parameter in the VCG and nVCG and neither in the nVDSG, but there was a decrease
      of mean values in the analyzed PPs under C4, with significant differences in
      medial/lateral COP excursion and COP mean velocity, and a significant decrease in
      the ratio C4/C1 of the mean velocity in VDSG. Therefore, WBV training had
      positive effects in the balance of DS adolescents although only under specific
      conditions, with vision and somatosensory input altered. The positive results of
      this study are encouraging and open a wide field of research, looking for the
      most efficient program for this population.

PMID- 23872531
TI  - The use of microfluidics in hemostasis: clinical diagnostics and biomimetic
      models of vascular injury.
AB  - PURPOSE OF REVIEW: This article reviews the application of microfluidic
      technologies in hemostasis. The emphasis is on promising developments in devices
      for clinical applications and novel approaches to modeling complex hemodynamics.
      RECENT FINDINGS: Microfluidics combined with micropatterning of prothrombotic
      substrates provides devices for measuring platelet function and coagulation with
      low blood volumes (~100 MUl) over a wide range of shear stresses. This technology
      has been applied to the diagnosis of bleeding and thrombotic disorders, as well
      as to dosing and monitoring of anticoagulation and antiplatelet agents.
      Microfluidic devices that mimic vascular geometries such as bifurcations,
      stenosis, and complex interconnected networks yield complex flow fields that have
      revealed new mechanisms of platelet adhesion and aggregation. Applying techniques
      from tissue engineering by endothelializing these networks is beginning to close
      the gap between in-vitro and in-vivo models of vascular injury. SUMMARY:
      Microfluidic technology enables researchers to create in-vitro models of vascular
      disease with unprecedented control of the biochemical and biophysical conditions.
      Two promising directions are flow-dependent clinical assays and biomimetic
      vascular networks. These approaches are particularly well suited for modeling the
      microvasculature. However, caution should be used when extrapolating results from
      microfluidic channels to the pathophysiology of thrombosis in large arteries and
      veins.

PMID- 23872532
TI  - Membrane binding properties of IRSp53-missing in metastasis domain (IMD) protein.
AB  - The 53-kDa insulin receptor substrate protein (IRSp53) organizes the actin
      cytoskeleton in response to stimulation of small GTPases, promoting the formation
      of cell protrusions such as filopodia and lamellipodia. IMD is the N-terminal 250
      amino acid domain (IRSp53/MIM Homology Domain) of IRSp53 (also called I-BAR),
      which can bind to negatively charged lipid molecules. Overexpression of IMD
      induces filopodia formation in cells and purified IMD assembles finger-like
      protrusions in reconstituted lipid membranes. IMD was shown by several groups to
      bundle actin filaments, but other groups showed that it also binds to membranes.
      IMD binds to negatively charged lipid molecules with preference to clusters of
      PI(4,5)P2. Here, we performed a range of different in vitro fluorescence
      experiments to determine the binding properties of the IMD to phospholipids. We
      used different constructs of large unilamellar vesicles (LUVETs), containing
      neutral or negatively charged phospholipids. We found that IMD has a stronger
      binding interaction with negatively charged PI(4,5)P2 or PS lipids than PS/PC or
      neutral PC lipids. The equilibrium dissociation constant for the IMD-lipid
      interaction falls into the 78-170MUM range for all the lipids tested. The solvent
      accessibility of the fluorescence labels on the IMD during its binding to lipids
      is also reduced as the lipids become more negatively charged. Actin affects the
      IMD-lipid interaction, depending on its polymerization state. Monomeric actin
      partially disrupts the binding, while filamentous actin can further stabilize the
      IMD-lipid interaction. 

PMID- 23872533
TI  - Thermodynamic and solution state NMR characterization of the binding of secondary
      and conjugated bile acids to STARD5.
AB  - STARD5 is a member of the STARD4 sub-family of START domain containing proteins
      specialized in the non-vesicular transport of lipids and sterols. We recently
      reported that STARD5 binds primary bile acids. Herein, we report on the
      biophysical and structural characterization of the binding of secondary and
      conjugated bile acids by STARD5 at physiological concentrations. We found that
      the absence of the 7alpha-OH group and its epimerization increase the affinity of
      secondary bile acids for STARD5. According to NMR titration and molecular
      modeling, the affinity depends mainly on the number and positions of the steroid
      ring hydroxyl groups and to a lesser extent on the presence or type of bile acid
      side-chain conjugation. Primary and secondary bile acids have different binding
      modes and display different positioning within the STARD5 binding pocket. The
      relative STARD5 affinity for the different bile acids studied is:
      DCA>LCA>CDCA>GDCA>TDCA>CA>UDCA. TCA and GCA do not bind significantly to STARD5.
      The impact of the ligand chemical structure on the thermodynamics of binding is
      discussed. The discovery of these new ligands suggests that STARD5 is involved in
      the cellular response elicited by bile acids and offers many entry points to
      decipher its physiological role. 

PMID- 23872534
TI  - Characterization of the human mitochondrial thiamine pyrophosphate transporter
      SLC25A19 minimal promoter: a role for NF-Y in regulating basal transcription.
AB  - Transcriptional regulation of expression of the human mitochondrial thiamine
      pyrophosphate transporter (the product of the SLC25A19 gene) is unknown. To
      understand this regulation, we cloned and characterized the 5'-regulatory region
      of the SLC25A19 gene (1,080 bp). The cloned fragment was found to possess
      promoter activity in transiently transfected human-derived liver HepG2 cells. 5'-
      and 3'-deletion analysis has identified the minimal region required for basal
      SLC25A19 promoter activity to be between -131 and +20 (using the distal
      transcriptional start site as +1). The minimal promoter lacks typical TATA motif
      and contains two inverted CCAAT boxes (binding sites for NF-Y transcriptional
      factor). By means of mutational analysis, the critical role of both the upstream
      and downstream CCAAT boxes in basal SLC25A19 promoter activity was established;
      however, each of these boxes alone was found to be unable to support promoter
      activity. EMSA and supershift EMSA (with the use of specific antibodies against
      NF-Y subunits) studies, as well as chromatin immunoprecipitation assay,
      demonstrated the binding of NF-Y to both CCAAT boxes in vitro and in vivo,
      respectively. The requirement for NF-Y in SLC25A19 promoter activity in vivo was
      directly confirmed by the use of a dominant negative NF-YA mutant in transiently
      transfected HepG2 cells. These studies report for the first time the
      characterization of the SLC25A19 promoter and demonstrate an essential role for
      NF-Y in its basal activity.

PMID- 23872535
TI  - The integrative expression and co-expression analysis of the AGO gene family in
      rice.
AB  - Argonautes (AGOs) play crucial roles in RNAi and related pathways in several
      species and regulate plant growth and development. However the investigation in
      rice argonautes (OsAGOs) remains elusive. Here we focused on the expression
      pattern and co-expression profiles of OsAGO genes. Microarray-based and qRT-PCR
      expression profiling of 19 OsAGO genes indicated that most OsAGOs expressed
      specifically and preferentially during stages of reproductive development, and
      exhibited preferential up-regulation in panicle stages. Six OsAGO genes showed
      specific up/down-regulation in response to Gibberellin A3 (GA3), Kinetin (KT), or
      1-Naphthaleneacetic acid (NAA) treatments. And three OsAGOs presented specific up
      regulation in response to light and dark treatments. Ten OsAGOs were co-expressed
      with Dicer-like (DCL), Double-stranded RNA Binding (DRB) and RNA-dependent RNA
      polymerase (RDR) genes, which were related with RNA processing including RNAi
      pathways. Twelve OsAGOs were correlated with 17 kinds of transcription factors
      involving diverse functions. Four OsAGOs RNAi plants were constructed, the
      expression level of co-expression genes, including DCL3, DRB2, RDR4 etc., were
      changed while OsAGOs were down-regulated in RNAi lines, providing experimental
      evidence for co-expression networks. The results provide new insights in
      understanding the biological pathways of OsAGO genes, as well as in selecting the
      candidate genes involved in RNA silencing mechanisms.

PMID- 23872537
TI  - A quantitative genetic basis for leaf morphology is revealed in a set of
      precisely defined tomato introgression lines.

PMID- 23872536
TI  - Whole mitochondrial DNA variations in hippocampal surgical specimens and blood
      samples with high-throughput sequencing: a case of mesial temporal lobe epilepsy
      with hippocampal sclerosis.
AB  - INTRODUCTION: Hippocampal sclerosis is the most common lesion in patients with
      mesial temporal lobe epilepsy. Recently, there has been growing evidence on the
      involvement of mitochondria also in sporadic forms of epilepsy. In addition, it
      has been increasingly argued that mitochondrial dysfunction has an important role
      in epileptogenesis and seizure generation in temporal lobe epilepsy. Although
      mtDNA polymorphisms have been identified as potential risk factors for
      neurological diseases, the link between homoplasmy and heteroplasmy within
      tissues is not clear. We investigated whether mitochondrial DNA (mtDNA)
      polymorphisms are involved in a case report of a patient with mesial temporal
      lobe epilepsy-hippocampal sclerosis (MTLE-HS). DESIGN: We report the whole genome
      mtDNA deep sequencing results and clinical features of a 36-year-old woman with
      MTLE-HS. We used pyrosequencing technology to sequence a whole mitochondrial
      genome isolated from six different regions of her brain and blood. To assess the
      possible role of mitochondrial DNA variations in affected tissues, we compared
      all specimens from different regions of the hippocampus and blood. RESULTS: In
      total, 35 homoplasmic and 18 heteroplasmic variations have been detected in 6
      different regions of the hippocampus and in blood samples. While the samples did
      not display any difference in homoplasmic variations, it has been shown that
      hippocampus regions contain more heteroplasmic variations than blood. The number
      of heteroplasmic variations was highest in the CA2 region of the brain and
      accumulated in ND2, ND4 and ND5 genes. Also, dentate and subiculum regions of the
      hippocampus had similar heteroplasmic variation profiles. DISCUSSION: We present
      a new rare example of parallel mutation at 16223 position. Our case suggests that
      defects in mitochondrial function might be underlying the pathogenesis of
      seizures in temporal lobe epilepsy.

PMID- 23872538
TI  - Gene networks and chromatin and transcriptional regulation of the phaseolin
      promoter in Arabidopsis.
AB  - The complete lack of seed storage protein expression in vegetative tissues and
      robust expression during embryogenesis makes seed development an ideal system to
      study tissue-specific expression of genes. The promoter for the Phaseolin (phas)
      gene, which encodes the major seed storage protein in bean (Phaseolus vulgaris),
      is activated in two sequential steps: Phaseolus vulgaris ABI3-like factor (Pv
      ALF)-dependent potentiation and abscisic acid-mediated activation. In this study,
      a heterologous in vivo Pv-ALF/phas-GUS (for beta-glucuronidase) expression system
      in transgenic Arabidopsis thaliana leaves was used in conjunction with the
      powerful RNA-Seq approach to capture transcriptional landscapes of phas promoter
      expression. Remarkably, expression of over 1300 genes from 11 functional
      categories coincided with changes in the transcriptional status of the phas
      promoter. Gene network analysis of induced genes and artificial microRNA-mediated
      loss-of-function genetic assays identified transcriptional regulators RINGLET 2
      (RLT2) and AINTEGUMENTA-LIKE 5 (AIL5) as being essential for phas transcription.
      Pv-ALF binding to the RLT2 and AIL5 promoter regions was confirmed by
      electrophoretic mobility shift assay. RLT2 and AIL5 knockdown lines displayed
      reduced expression of several endogenous seed genes, suggesting that these
      factors are involved in activation of endogenous Arabidopsis seed storage gene
      expression. Overall, the identification of these key factors involved in phas
      activation provides important insight into the two-step transcriptional
      regulation of seed-specific gene expression. 

PMID- 23872540
TI  - A 3-day delay in synovial fluid crystal identification did not hinder the
      reliable detection of monosodium urate and calcium pyrophosphate crystals.
AB  - BACKGROUND: Arthrocentesis is an essential emergency step in managing patients
      with acute arthritis. To identify a bacterial infection, Gram staining is
      performed promptly. However, crystal analysis may not be immediately performed in
      many facilities. Being considered not to be stable over time, synovial fluid (SF)
      is sometimes discarded instead of being stored for crystal identification.
      OBJECTIVE: The aim of this study was to assess the detectability of monosodium
      urate (MSU) and calcium pyrophosphate (CPP) crystals in SF over a period of 3
      days. METHODS: Consecutive SF samples from 75 joints were analyzed for MSU, CPP
      crystals, and pH. Two independent observers evaluated the samples by regular
      light and polarization microscopy immediately after arthrocentesis and after 1,
      2, and 3 days at room temperature or at 4 degrees C. RESULTS: Of 75 samples, 27
      contained crystals (16 MSU, 6 CPP, 5 both); semiquantitative counts of both MSU
      and CPP crystals did not change significantly after 3 days. There was no new
      formation of crystals in any of the crystal-negative samples, which was
      independent of the storage temperature. Synovial fluid pH was not predictive of
      crystals and did not change over time. CONCLUSIONS: Although immediate workup for
      microbiology, including Gram stain and culture, is indispensable and well
      established, crystal analysis may at times not be immediately performed. Our
      study suggests that when crystal identification cannot be done immediately, it
      can be safely performed up to 3 days after arthrocentesis when SF is stored at 4
      degrees C or even at stable room temperature (20 degrees C).

PMID- 23872541
TI  - Disease severity in adult patients of Turkish ancestry with familial
      mediterranean fever living in Germany or Turkey. Does the country of residence
      affect the course of the disease?
AB  - BACKGROUND: The environment may affect the course of familial Mediterranean fever
      (FMF). OBJECTIVE: The objective of this study was to compare disease severity
      between adult FMF patients in Turkey (TR) and Germany (G). METHODS: Adult FMF
      patients of Turkish ancestry on colchicine living in Turkey (n = 40) or G (n =
      35) were compared. Disease severity, C-reactive protein (CRP), and erythrocyte
      sedimentation rate were assessed. RESULTS: Groups differed significantly in the
      following aspects: age at onset of disease (TR: 15.6, G: 10.8 years; P = 0.02),
      delay between onset and initiation of colchicine treatment (TR: 6.8 years, G:
      14.9 years; P < 0.001), female gender (TR: 80%, G: 57.1%; P = 0.04), and duration
      of disease (TR: 14.4 years, G: 23.4 years; P < 0.001). There was no significant
      difference in colchicine treatment concerning average dosing and duration of
      therapy. No significant difference could be found between the 2 groups in CRP and
      disease severity as assessed by the score of Pras et al. (Am J Med Genet.
      1998;75:216-219) even after adjusting for potential confounding variables. Mean
      erythrocyte sedimentation rate was significantly higher among patients living in
      G (TR: 13.2 mm/first hour, G: 26.3 mm/first hour; P < 0.001). Among patients
      living in Germany, there was a significant difference in age at FMF onset
      depending on their country of birth (born in TR: 14.9 years, born in G: 6.9
      years; P = 0.0001). CONCLUSIONS: In adult FMF patients living in Turkey or
      Germany, no difference in disease activity or CRP could be found. German patients
      were younger at onset of disease and had a longer delay between onset and
      initiation of colchicine treatment.

PMID- 23872539
TI  - A quantitative genetic basis for leaf morphology in a set of precisely defined
      tomato introgression lines.
AB  - Introgression lines (ILs), in which genetic material from wild tomato species is
      introgressed into a domesticated background, have been used extensively in tomato
      (Solanum lycopersicum) improvement. Here, we genotype an IL population derived
      from the wild desert tomato Solanum pennellii at ultrahigh density, providing the
      exact gene content harbored by each line. To take advantage of this information,
      we determine IL phenotypes for a suite of vegetative traits, ranging from leaf
      complexity, shape, and size to cellular traits, such as stomatal density and
      epidermal cell phenotypes. Elliptical Fourier descriptors on leaflet outlines
      provide a global analysis of highly heritable, intricate aspects of leaf
      morphology. We also demonstrate constraints between leaflet size and leaf
      complexity, pavement cell size, and stomatal density and show independent
      segregation of traits previously assumed to be genetically coregulated. Meta
      analysis of previously measured traits in the ILs shows an unexpected
      relationship between leaf morphology and fruit sugar levels, which RNA-Seq data
      suggest may be attributable to genetically coregulated changes in fruit
      morphology or the impact of leaf shape on photosynthesis. Together, our results
      both improve upon the utility of an important genetic resource and attest to a
      complex, genetic basis for differences in leaf morphology between natural
      populations. 

PMID- 23872542
TI  - Treatment of multicentric reticulohistiocytosis with tocilizumab.
AB  - Multicentric reticulohistiocytosis (MRH) is a rare multisystem, granulomatous
      debilitating disease. It affects the skin with a nodular diffuse dermatitis and
      the joints with a severe, potentially deforming, and handicapping arthritis. No
      standardized therapy exists, it is a disease with heterogeneous severity, and
      therefore, a diversity of therapeutic responses has been published.Current
      experience with anti-tumor necrosis factor agents in disease-modifying
      antirheumatic drug-refractory MRH cases is encouraging, and other agents such as
      bisphosphonates have proven effective as well. Histological analysis of the
      granulomatous inflammatory lesions have shown the presence of cytokines including
      tumor necrosis factor alpha, interleukin 1, and interleukin 6; the presence of
      the latter makes tocilizumab a plausible alternative.In this article, we report a
      35-year-old woman with MRH refractory to a combined scheme of prednisone and
      methotrexate, both at high doses, and who received tocilizumab achieving
      remission on both cutaneous and articular symptoms. Our patient markedly improved
      by the second infusion (8 mg/kg monthly), and after 9 infusions, she remained
      asymptomatic; no toxicity was detected. Tocilizumab could be an alternative for
      disease-modifying antirheumatic drug-refractory MRH. 

PMID- 23872543
TI  - Leukocytoclastic vasculitis secondary to erysipelas: an unusual case of
      noncryoglobulinemic vasculitis in a hepatitis C patient.

PMID- 23872544
TI  - Response of primary erythromelalgia to pregabalin therapy.

PMID- 23872545
TI  - Psoriasis and psoriatic arthropathy: historical aspects: part II.

PMID- 23872546
TI  - Necrotizing fasciitis in patients on methotrexate therapy.

PMID- 23872547
TI  - Consumer perspectives on pediatric rheumatology care and service delivery: a
      qualitative study.
AB  - OBJECTIVES: This study aimed to elicit parental and adolescent perspectives on
      pediatric rheumatology care and service delivery and to describe the impact of
      this process on a proposed model of care addressing pediatric rheumatology
      service delivery. METHODS: Adolescents with juvenile idiopathic arthritis (JIA)
      and caregivers in New South Wales, Australia, participated in focus groups or
      semistructured interviews conducted from August to November 2011. Transcripts
      were coded and thematically analyzed. Changes to the model of care as a result of
      this process were identified. RESULTS: Thirty-seven parents and 13 adolescents
      participated. Five main themes were identified including (1) optimize service
      efficiency (promoting awareness about JIA, minimizing delays in diagnosis and
      treatment, continuity of care, holistic and integrated care, access to health
      care providers with JIA expertise, extending pharmacy services, regional outreach
      programs); (2) transitional care (trust and rapport with the adult
      rheumatologist, comprehensive information transfer of patient history); (3)
      psychosocial support (social and financial aid, mental health services,
      vocational guidance, peer support); (4) informational needs (medicine adverse
      effects, nutritional guidance, pain management, administering medications,
      obtaining medical equipment); and (5) school-based support and advocacy (to
      promote acceptance, provide academic assistance, facilitate environmental
      modifications, offer alternative activities). The model of care was extended to
      include consumer-focused concerns. CONCLUSIONS: A well-coordinated network of
      services, timely and accurate information about the illness, treatment and
      support services, adequate pharmacy support, and school-based advocacy are
      proposed to be needed to ensure pediatric rheumatology services that are
      accessible and responsive to the needs of patients and their families.

PMID- 23872548
TI  - Pneumocystis jirovecii pneumonia in systemic lupus erythematosus from southern
      Taiwan.
AB  - BACKGROUND: Opportunistic infection has been documented in systemic lupus
      erythematosus with special attention paid to Pneumocystis jirovecii because of
      the significant morbidity and high mortality. OBJECTIVES: The limited large-scale
      investigations covering P. jirovecii pneumonia (PCP) in systemic lupus
      erythematosus following biologics or immunosuppressants therapy prompted us to
      perform this study in southern Taiwan. METHODS: A retrospective study was
      completed in 858 hospitalized lupus patients from January 2000 to December 2011.
      The definite diagnosis of PCP was made by the laboratory detection of
      Pneumocystis organisms together with consistent clinical and radiological
      manifestations of PCP. Positive polymerase chain reaction results of sputum
      samples were not regarded as infection in this study, unless P. jirovecii was the
      sole pathogen found and pulmonary manifestations resolved following antibiotics
      for PCP treatment alone. RESULTS: The laboratory identification of Pneumocystis
      organisms depended on lung biopsy in 2 cases and bronchoalveolar lavage in 3
      patients. Five cases, 2 women and 3 men aged 30 to 50 years (41.8 +/- 8.8 years),
      were identified with a 0.6% incidence. None received chemoprophylactics against
      P. jirovecii infection. All had lupus nephritis and lymphopenia with low CD4 T
      cell counts. Prior usages of higher daily prednisolone dosages and concomitant
      biologics or immunosuppressants were observed in all patients. Pneumocystis
      jirovecii pneumonia contributed to a high mortality rate (60%). CONCLUSIONS: We
      report the rare occurrence but high mortality of PCP infection in this study. A
      consensus guideline addressing prophylactic antibiotics against Pneumocystis
      organisms in highest-risk lupus patients on biologics or immunosuppressants could
      be helpful in guiding their management.

PMID- 23872549
TI  - Ainhum (dactylolysis spontanea): a case with hands and feet involvement.
AB  - Dactylolysis spontanea is a rare disease of unknown etiology, basically
      restricted to digits without systemic involvement. It evolves, in the form of a
      local constriction, affecting typically the distal phalanx of the fifth toe,
      rarely involving other toes and even more rarely involving fingers as in the case
      described herein. 

PMID- 23872550
TI  - Connective tissue disease following hepatitis B vaccination.

PMID- 23872551
TI  - Suspected hydroxychloroquine-associated QT-interval prolongation in a patient
      with systemic lupus erythematosus.

PMID- 23872552
TI  - Transcriptional regulation of the growth-regulated oncogene alpha gene by early
      growth response protein-1 in response to tumor necrosis factor alpha stimulation.
AB  - Growth-regulated oncogene alpha (GROalpha) plays an important role in a wide
      range of normal and pathological conditions, including inflammation,
      angiogenesis, wound healing, tumor invasion, and metastasis. Egr-1 is a member of
      the zinc-finger transcription factor family induced by diverse stimuli, including
      TNFalpha. However, the role of Egr-1 in GROalpha expression was previously
      unknown. This study shows that Egr-1 directly binds to the GROalpha promoter and
      transactivates the GROalpha gene. Silencing of Egr-1 by expression of Egr-1 siRNA
      abrogated TNFalpha-induced GROalpha transcription. We also found that Egr-1
      mediates ERK and JNK MAPK-dependent GROalpha transcription upon TNFalpha
      stimulation. Our findings suggest that Egr-1 may play an important role in tumor
      development through transactivation of the GROalpha gene in response to TNFalpha
      within the tumor microenvironment. 

PMID- 23872553
TI  - Footwear recommendations and patterns among orthopaedic foot and ankle surgeons:
      a survey.
AB  - BACKGROUND: Foot and ankle surgeons are in a unique position to educate patients
      about the importance of proper footwear. Neither their recommendations regarding
      shoe selection nor their own footwear patterns have previously been reported.
      METHODS: A total of 866 members of the American Orthopaedic Foot & Ankle Society
      (AOFAS) were asked to complete a survey via the Internet. Topics included
      specific shoe brands recommended to patients, how attributes of footwear are
      communicated, and respondents' footwear habits. RESULTS: In all, 276 (32%)
      surgeons responded, and 64% recommended New Balance athletic shoes to patients;
      26% did not recommend specific brands. It was found that 50% wear New Balance
      athletic shoes; 25% wear Nike. Rockport (27%) and SAS (27%) were the most
      recommended dress shoes. In all, 76% are familiar with AOFAS guidelines for
      proper shoe fit, but only 56% educated their patients about the guidelines; 43%
      do not consider what patients might think of their shoes when selecting what to
      wear in the clinical setting. CONCLUSIONS: Despite the multitude of different
      brands, several were commonly recommended. Respondents seem to be aware of the
      impact of their own shoe selection on patients' perspectives of footwear, but
      many do not consider themselves role models for proper footwear.

PMID- 23872554
TI  - Detoxification of mercury by methanobactin from Methylosinus trichosporium OB3b.
AB  - Many methanotrophs have been shown to synthesize methanobactin, a novel biogenic
      copper-chelating agent or chalkophore. Methanobactin binds copper via two
      heterocyclic rings with associated enethiol groups. The structure of
      methanobactin suggests that it can bind other metals, including mercury. Here we
      report that methanobactin from Methylosinus trichosporium OB3b does indeed bind
      mercury when added as HgCl2 and, in doing so, reduced toxicity associated with
      Hg(II) for both Alphaproteobacteria methanotrophs, including M. trichosporium
      OB3b, M. trichosporium OB3b DeltambnA (a mutant defective in methanobactin
      production), and Methylocystis sp. strain SB2, and a Gammaproteobacteria
      methanotroph, Methylomicrobium album BG8. Mercury binding by methanobactin was
      evident in both the presence and absence of copper, despite the fact that
      methanobactin had a much higher affinity for copper due to the rapid and
      irreversible binding of mercury by methanobactin. The formation of a gray
      precipitate suggested that Hg(II), after being bound by methanobactin, was
      reduced to Hg(0) but was not volatilized. Rather, mercury remained associated
      with methanobactin and was also found associated with methanotrophic biomass. It
      thus appears that although the mercury-methanobactin complex was cell associated,
      mercury was not removed from methanobactin. The amount of biomass-associated
      mercury in the presence of methanobactin from M. trichosporium OB3b was greatest
      for M. trichosporium wild-type strain OB3b and the DeltambnA mutant and least for
      M. album BG8, suggesting that methanotrophs may have selective methanobactin
      uptake systems that may be based on TonB-dependent transporters but that such
      uptake systems exhibit a degree of infidelity. 

PMID- 23872555
TI  - Characterization of the Burkholderia thailandensis SOS response by using whole
      transcriptome shotgun sequencing.
AB  - The bacterial SOS response is a well-characterized regulatory network encoded by
      most prokaryotic bacterial species and is involved in DNA repair. In addition to
      nucleic acid repair, the SOS response is involved in pathogenicity, stress
      induced mutagenesis, and the emergence and dissemination of antibiotic
      resistance. Using high-throughput sequencing technology (SOLiD RNA-Seq), we
      analyzed the Burkholderia thailandensis global SOS response to the
      fluoroquinolone antibiotic, ciprofloxacin (CIP), and the DNA-damaging chemical,
      mitomycin C (MMC). We demonstrate that a B. thailandensis recA mutant (RU0643) is
      ~4-fold more sensitive to CIP in contrast to the parental strain B. thailandensis
      DW503. Our RNA-Seq results show that CIP and MMC treatment (P < 0.01) resulted in
      the differential expression of 344 genes in B. thailandensis and 210 genes in
      RU0643. Several genes associated with the SOS response were induced and include
      lexA, uvrA, dnaE, dinB, recX, and recA. At the genome-wide level, we found an
      overall decrease in gene expression, especially for genes involved in amino acid
      and carbohydrate transport and metabolism, following both CIP and MMC exposure.
      Interestingly, we observed the upregulation of several genes involved in
      bacterial motility and enhanced transcription of a B. thailandensis genomic
      island encoding a Siphoviridae bacteriophage designated E264. Using B.
      thailandensis plaque assays and PCR with B. mallei ATCC 23344 as the host, we
      demonstrate that CIP and MMC exposure in B. thailandensis DW503 induces the
      transcription and translation of viable bacteriophage in a RecA-dependent manner.
      This is the first report of the SOS response in Burkholderia spp. to DNA-damaging
      agents. We have identified both common and unique adaptive responses of B.
      thailandensis to chemical stress and DNA damage. 

PMID- 23872556
TI  - Intragenomic heterogeneity of 16S rRNA genes causes overestimation of prokaryotic
      diversity.
AB  - Ever since Carl Woese introduced the use of 16S rRNA genes for determining the
      phylogenetic relationships of prokaryotes, this method has been regarded as the
      "gold standard" in both microbial phylogeny and ecology studies. However,
      intragenomic heterogeneity within 16S rRNA genes has been reported in many
      investigations and is believed to bias the estimation of prokaryotic diversity.
      In the current study, 2,013 completely sequenced genomes of bacteria and archaea
      were analyzed and intragenomic heterogeneity was found in 952 genomes (585
      species), with 87.5% of the divergence detected being below the 1% level. In
      particular, some extremophiles (thermophiles and halophiles) were found to harbor
      highly divergent 16S rRNA genes. Overestimation caused by 16S rRNA gene
      intragenomic heterogeneity was evaluated at different levels using the full
      length and partial 16S rRNA genes usually chosen as targets for pyrosequencing.
      The result indicates that, at the unique level, full-length 16S rRNA genes can
      produce an overestimation of as much as 123.7%, while at the 3% level, an
      overestimation of 12.9% for the V6 region may be introduced. Further analysis
      showed that intragenomic heterogeneity tends to concentrate in specific
      positions, with the V1 and V6 regions suffering the most intragenomic
      heterogeneity and the V4 and V5 regions suffering the least intragenomic
      heterogeneity in bacteria. This is the most up-to-date overview of the diversity
      of 16S rRNA genes within prokaryotic genomes. It not only provides general
      guidance on how much overestimation can be introduced when applying 16S rRNA gene
      based methods, due to its intragenomic heterogeneity, but also recommends that,
      for bacteria, this overestimation be minimized using primers targeting the V4 and
      V5 regions. 

PMID- 23872557
TI  - Transcriptome-based characterization of interactions between Saccharomyces
      cerevisiae and Lactobacillus delbrueckii subsp. bulgaricus in lactose-grown
      chemostat cocultures.
AB  - Mixed populations of Saccharomyces cerevisiae yeasts and lactic acid bacteria
      occur in many dairy, food, and beverage fermentations, but knowledge about their
      interactions is incomplete. In the present study, interactions between
      Saccharomyces cerevisiae and Lactobacillus delbrueckii subsp. bulgaricus, two
      microorganisms that co-occur in kefir fermentations, were studied during
      anaerobic growth on lactose. By combining physiological and transcriptome
      analysis of the two strains in the cocultures, five mechanisms of interaction
      were identified. (i) Lb. delbrueckii subsp. bulgaricus hydrolyzes lactose, which
      cannot be metabolized by S. cerevisiae, to galactose and glucose. Subsequently,
      galactose, which cannot be metabolized by Lb. delbrueckii subsp. bulgaricus, is
      excreted and provides a carbon source for yeast. (ii) In pure cultures, Lb.
      delbrueckii subsp. bulgaricus grows only in the presence of increased CO2
      concentrations. In anaerobic mixed cultures, the yeast provides this CO2 via
      alcoholic fermentation. (iii) Analysis of amino acid consumption from the defined
      medium indicated that S. cerevisiae supplied alanine to the bacterium. (iv) A
      mild but significant low-iron response in the yeast transcriptome, identified by
      DNA microarray analysis, was consistent with the chelation of iron by the lactate
      produced by Lb. delbrueckii subsp. bulgaricus. (v) Transcriptome analysis of Lb.
      delbrueckii subsp. bulgaricus in mixed cultures showed an overrepresentation of
      transcripts involved in lipid metabolism, suggesting either a competition of the
      two microorganisms for fatty acids or a response to the ethanol produced by S.
      cerevisiae. This study demonstrates that chemostat-based transcriptome analysis
      is a powerful tool to investigate microbial interactions in mixed populations. 

PMID- 23872558
TI  - Characterization of AmiBA2446, a novel bacteriolytic enzyme active against
      Bacillus species.
AB  - There continues to be a need for developing efficient and environmentally
      friendly treatments for Bacillus anthracis, the causative agent of anthrax. One
      emerging approach for inactivation of vegetative B. anthracis is the use of
      bacteriophage endolysins or lytic enzymes encoded by bacterial genomes
      (autolysins) with highly evolved specificity toward bacterium-specific
      peptidoglycan cell walls. In this work, we performed in silico analysis of the
      genome of Bacillus anthracis strain Ames, using a consensus binding domain amino
      acid sequence as a probe, and identified a novel lytic enzyme that we termed
      AmiBA2446. This enzyme exists as a homodimer, as determined by size exclusion
      studies. It possesses N-acetylmuramoyl-l-alanine amidase activity, as determined
      from liquid chromatography-mass spectrometry (LC-MS) analysis of muropeptides
      released due to the enzymatic digestion of peptidoglycan. Phylogenetic analysis
      suggested that AmiBA2446 was an autolysin of bacterial origin. We characterized
      the effects of enzyme concentration and phase of bacterial growth on bactericidal
      activity and observed close to a 5-log reduction in the viability of cells of
      Bacillus cereus 4342, a surrogate for B. anthracis. We further tested the
      bactericidal activity of AmiBA2446 against various Bacillus species and
      demonstrated significant activity against B. anthracis and B. cereus strains. We
      also demonstrated activity against B. anthracis spores after pretreatment with
      germinants. AmiBA2446 enzyme was also stable in solution, retaining its activity
      after 4 months of storage at room temperature. 

PMID- 23872559
TI  - Enantioselective dehydrochlorination of delta-Hexachlorocyclohexane and delta
      Pentachlorocyclohexene by LinA1 and LinA2 from Sphingobium indicum B90A.
AB  - delta-Hexachlorocyclohexane (delta-HCH), one of the prevalent isomers of
      technical HCH, was enantioselectively dehydrochlorinated by the
      dehydrochlorinases LinA1 and LinA2 from Sphingobium indicum B90A to the very same
      delta-pentachlorocyclohexene enantiomer. Racemic delta-pentachlorocyclohexene,
      however, was transformed with opposite enantioselectivities by the two enzymes. A
      transformation pathway based on an anti-1,2-elimination, followed by a syn-1,4
      elimination and a subsequent syn-1,2-elimination is postulated. 

PMID- 23872560
TI  - Unique contribution of the cell wall-binding endoglucanase G to the cellulolytic
      complex in Clostridium cellulovorans.
AB  - The cellulosomes produced by Clostridium cellulovorans are organized by the
      specific interactions between the cohesins in the scaffolding proteins and the
      dockerins of the catalytic components. Using a cohesin biomarker, we identified a
      cellulosomal enzyme which belongs to the glycosyl hydrolase family 5 and has a
      domain of unknown function 291 (DUF291) with functions similar to those of the
      surface layer homology domain in C. cellulovorans. The purified endoglucanase G
      (EngG) had the highest synergistic degree with exoglucanase (ExgS) in the
      hydrolysis of crystalline cellulose (EngG/ExgS ratio = 3:1; 1.71-fold). To
      measure the binding affinity of the dockerins in EngG for the cohesins of the
      main scaffolding protein, a competitive enzyme-linked interaction assay was
      performed. Competitors, such as ExgS, reduced the percentage of EngG that were
      bound to the cohesins to less than 20%; the results demonstrated that the
      cohesins prefer to bind to the common cellulosomal enzymes rather than to EngG.
      Additionally, in surface plasmon resonance analysis, the dockerin in EngG had a
      relatively weak affinity (30- to 123-fold) for cohesins compared with the other
      cellulosomal enzymes. In the cell wall affinity assay, EngG anchored to the cell
      surfaces of C. cellulovorans using its DUF291 domain. Immunofluorescence
      microscopy confirmed the cell surface display of the EngG complex. These results
      indicated that in C. cellulovorans, EngG assemble into both the cellulolytic
      complex and the cell wall complex to aid in the hydrolysis of cellulose
      substrates. 

PMID- 23872561
TI  - Comparative proteomic analysis of Streptomyces lividans Wild-Type and ppk mutant
      strains reveals the importance of storage lipids for antibiotic biosynthesis.
AB  - Streptomyces lividans TK24 is a strain that naturally produces antibiotics at low
      levels, but dramatic overproduction of antibiotics occurs upon interruption of
      the ppk gene. However, the role of the Ppk enzyme in relation to the regulation
      of antibiotic biosynthesis remains poorly understood. In order to gain a better
      understanding of the phenotype of the ppk mutant, the proteomes of the wild-type
      (wt) and ppk mutant strains, grown for 96 h on R2YE medium limited in phosphate,
      were analyzed. Intracellular proteins were separated on two-dimensional (2D)
      gels, spots were quantified, and those showing a 3-fold variation or more were
      identified by mass spectrometry. The expression of 12 proteins increased and that
      of 29 decreased in the ppk mutant strain. Our results suggested that storage
      lipid degradation rather than hexose catabolism was taking place in the mutant.
      In order to validate this hypothesis, the triacylglycerol contents of the wt and
      ppk mutant strains of S. lividans as well as that of Streptomyces coelicolor
      M145, a strain that produces antibiotics at high levels and is closely related to
      S. lividans, were assessed using electron microscopy and thin-layer
      chromatography. These studies highlighted the large difference in triacylglycerol
      contents of the three strains and confirmed the hypothetical link between storage
      lipid metabolism and antibiotic biosynthesis in Streptomyces. 

PMID- 23872562
TI  - Development of a gene knockout system using mobile group II introns (Targetron)
      and genetic disruption of acid production pathways in Clostridium beijerinckii.
AB  - Clostridium beijerinckii is a well-known solvent-producing microorganism with
      great potential for biofuel and biochemical production. To better understand and
      improve the biochemical pathway to solvents, the development of genetic tools for
      engineering C. beijerinckii is highly desired. Based on mobile group II intron
      technology, a targetron gene knockout system was developed for C. beijerinckii in
      this study. This system was successfully employed to disrupt acid production
      pathways in C. beijerinckii, leading to pta (encoding phosphotransacetylase)- and
      buk (encoding butyrate kinase)-negative mutants. In addition to experimental
      characterization, the mutant phenotypes were analyzed in the context of our C.
      beijerinckii genome-scale model. Compared to those of the parental strain (C.
      beijerinckii 8052), acetate production in the pta mutant was substantially
      reduced and butyrate production was remarkably increased, while solvent
      production was dependent on the growth medium. The pta mutant also produced much
      higher levels of lactate, suggesting that disrupting pta influenced the energy
      generation and electron flow pathways. In contrast, acetate and butyrate
      production in the buk mutant was generally similar to that of the wild type, but
      solvent production was consistently 20 to 30% higher and glucose consumption was
      more rapid and complete. Our results suggest that the acid and solvent production
      of C. beijerinckii can be effectively altered by disrupting the acid production
      pathways. As the gene disruption method developed in this study does not leave
      any antibiotic marker in a disrupted allele, multiple and high-throughput gene
      disruption is feasible for elucidating genotype and phenotype relationships in C.
      beijerinckii. 

PMID- 23872563
TI  - Abundant DNase I-sensitive bacterial DNA in healthy porcine lungs and its
      implications for the lung microbiome.
AB  - Human lungs are constantly exposed to bacteria in the environment, yet the
      prevailing dogma is that healthy lungs are sterile. DNA sequencing-based studies
      of pulmonary bacterial diversity challenge this notion. However, DNA-based
      microbial analysis currently fails to distinguish between DNA from live bacteria
      and that from bacteria that have been killed by lung immune mechanisms,
      potentially causing overestimation of bacterial abundance and diversity. We
      investigated whether bacterial DNA recovered from lungs represents live or dead
      bacteria in bronchoalveolar lavage (BAL) fluid and lung samples in young healthy
      pigs. Live bacterial DNA was DNase I resistant and became DNase I sensitive upon
      human antimicrobial-mediated killing in vitro. We determined live and total
      bacterial DNA loads in porcine BAL fluid and lung tissue by comparing DNase I
      treated versus untreated samples. In contrast to the case for BAL fluid, we were
      unable to culture bacteria from most lung homogenates. Surprisingly, total
      bacterial DNA was abundant in both BAL fluid and lung homogenates. In BAL fluid,
      63% was DNase I sensitive. In 6 out of 11 lung homogenates, all bacterial DNA was
      DNase I sensitive, suggesting a predominance of dead bacteria; in the remaining
      homogenates, 94% was DNase I sensitive, and bacterial diversity determined by 16S
      rRNA gene sequencing was similar in DNase I-treated and untreated samples.
      Healthy pig lungs are mostly sterile yet contain abundant DNase I-sensitive DNA
      from inhaled and aspirated bacteria killed by pulmonary host defense mechanisms.
      This approach and conceptual framework will improve analysis of the lung
      microbiome in disease. 

PMID- 23872564
TI  - The carbohydrate metabolism signature of lactococcus lactis strain A12 reveals
      its sourdough ecosystem origin.
AB  - Lactococcus lactis subsp. lactis strain A12 was isolated from sourdough. Combined
      genomic, transcriptomic, and phenotypic analyses were performed to understand its
      survival capacity in the complex sourdough ecosystem and its role in the
      microbial community. The genome sequence comparison of strain A12 with strain
      IL1403 (a derivative of an industrial dairy strain) revealed 78 strain-specific
      regions representing 23% of the total genome size. Most of the strain-specific
      genes were involved in carbohydrate metabolism and are potentially required for
      its persistence in sourdough. Phenotype microarray, growth tests, and analysis of
      glycoside hydrolase content showed that strain A12 fermented plant-derived
      carbohydrates, such as arabinose and alpha-galactosides. Strain A12 exhibited
      specific growth rates on raffinose that were as high as they were on glucose and
      was able to release sucrose and galactose outside the cell, providing soluble
      carbohydrates for sourdough microflora. Transcriptomic analysis identified genes
      specifically induced during growth on raffinose and arabinose and reveals an
      alternative pathway for raffinose assimilation to that used by other lactococci. 

PMID- 23872565
TI  - Alternative sigma factor sigmaE has an important role in stress tolerance of
      Yersinia pseudotuberculosis IP32953.
AB  - Yersinia pseudotuberculosis is an important pathogen that probably survives well
      in the modern food chain. However, little is known about the mechanisms that
      allow the growth of this pathogen in foods under stress conditions. The
      expression of rpoE encoding sigma(E) was defined by quantitative real-time
      reverse transcription-PCR. Expression of rpoE was induced at 3 degrees C, 37
      degrees C, and 42 degrees C, under exposure to 3% NaCl, 3% ethanol, or high and
      low pH, in relation to its expression at the optimum growth temperature of 28
      degrees C of Y. pseudotuberculosis. Mutation of rpoE either impaired or abolished
      growth under stresses caused by low or high temperature, low pH, and ethanol. In
      addition, the growth temperature range of the mutant was significantly diminished
      compared to that of the wild-type strain IP32953. The results were confirmed with
      complementation of the mutant. Thus, sigma(E) plays a significant role in the
      stress tolerance of Y. pseudotuberculosis IP32953 and probably contributes to the
      survival of this pathogen in the food chain. 

PMID- 23872566
TI  - Clostridium acidurici electron-bifurcating formate dehydrogenase.
AB  - Cell extracts of uric acid-grown Clostridium acidurici catalyzed the coupled
      reduction of NAD(+) and ferredoxin with formate at a specific activity of 1.3
      U/mg. The enzyme complex catalyzing the electron-bifurcating reaction was
      purified 130-fold and found to be composed of four subunits encoded by the gene
      cluster hylCBA-fdhF2. 

PMID- 23872567
TI  - Diet complexity and estrogen receptor beta status affect the composition of the
      murine intestinal microbiota.
AB  - Intestinal microbial dysbiosis contributes to the dysmetabolism of luminal
      factors, including steroid hormones (sterones) that affect the development of
      chronic gastrointestinal inflammation and the incidence of sterone-responsive
      cancers of the breast, prostate, and colon. Little is known, however, about the
      role of specific host sterone nucleoreceptors, including estrogen receptor beta
      (ERbeta), in microbiota maintenance. Herein, we test the hypothesis that ERbeta
      status affects microbiota composition and determine if such compositionally
      distinct microbiota respond differently to changes in diet complexity that favor
      Proteobacteria enrichment. To this end, conventionally raised female ERbeta(+/+)
      and ERbeta(-/-) C57BL/6J mice (mean age of 27 weeks) were initially reared on
      8604, a complex diet containing estrogenic isoflavones, and then fed AIN-76, an
      isoflavone-free semisynthetic diet, for 2 weeks. 16S rRNA gene surveys revealed
      that the fecal microbiota of 8604-fed mice and AIN-76-fed mice differed, as
      expected. The relative diversity of Proteobacteria, especially the
      Alphaproteobacteria and Gammaproteobacteria, increased significantly following
      the transition to AIN-76. Distinct patterns for beneficial Lactobacillales were
      exclusive to and highly abundant among 8604-fed mice, whereas several
      Proteobacteria were exclusive to AIN-76-fed mice. Interestingly, representative
      orders of the phyla Proteobacteria, Bacteroidetes, and Firmicutes, including the
      Lactobacillales, also differed as a function of murine ERbeta status. Overall,
      these interactions suggest that sterone nucleoreceptor status and diet complexity
      may play important roles in microbiota maintenance. Furthermore, we envision that
      this model for gastrointestinal dysbiosis may be used to identify novel
      probiotics, prebiotics, nutritional strategies, and pharmaceuticals for the
      prevention and resolution of Proteobacteria-rich dysbiosis.

PMID- 23872568
TI  - Extending the cellulosome paradigm: the modular Clostridium thermocellum
      cellulosomal serpin PinA is a broad-spectrum inhibitor of subtilisin-like
      proteases.
AB  - Clostridium thermocellum encodes a cellulosomal, modular, and thermostable serine
      protease inhibitor (serpin), PinA. PinA stability but not inhibitory activity is
      affected by the Fn(III) and Doc(I) domains, and PinA is a broad inhibitor of
      subtilisin-like proteases and may play a key role in protecting the cellulosome
      from protease attack. 

PMID- 23872569
TI  - Utilization of heme as an iron source by marine Alphaproteobacteria in the
      Roseobacter clade.
AB  - The bioavailability and utilization of porphyrin-bound iron, specifically heme,
      by marine microorganisms have rarely been examined. This study used Ruegeria sp.
      strain TrichCH4B as a model organism to study heme acquisition by a member of the
      Roseobacter clade. Analogs of known heme transporter proteins were found within
      the Ruegeria sp. TrichCH4B genome. The identified heme uptake and utilization
      system appears to be functional, as the heme genes were upregulated under iron
      stress, the bacterium could grow on ferric-porphyrin complexes as the sole iron
      source, and internalization of (55) Fe from ferric protoporphyrin IX was
      observed. The potential ability to utilize heme in the Roseobacter clade appears
      to be common, as half of the isolates in the RoseoBase database were found to
      have a complete heme uptake system. A degenerate primer set was designed and
      successfully used to identify the putative heme oxygenase gene (hmus) in the
      roseobacter heme uptake system from diverse nonenriched marine environments. This
      study found that members of the Roseobacter clade are capable of utilizing heme
      as an iron source and that this capability may be present in all types of marine
      environments. The results of this study add a new perspective to the current
      picture of iron cycling in marine systems, whereby relatively refractory
      intracellular pools of heme-bound iron may be taken up quickly and directly
      reincorporated into living bacteria without previous degradation or the necessity
      of a siderophore intermediate.

PMID- 23872570
TI  - Distribution of virulence genes in clinical and environmental Vibrio cholerae
      strains in Bangladesh.
AB  - Vibrio cholerae, an environmental organism, is a facultative human pathogen.
      Here, we report the virulence profiles, comprising 18 genetic markers, of 102
      clinical and 692 environmental V. cholerae strains isolated in Bangladesh between
      March 2004 and January 2006, showing the variability of virulence determinants
      within the context of public health. 

PMID- 23872571
TI  - Genetic characterization of atypical enteropathogenic Escherichia coli isolates
      from ewes' milk, sheep farm environments, and humans by multilocus sequence
      typing and pulsed-field gel electrophoresis.
AB  - A collection of 81 isolates of enteropathogenic Escherichia coli (EPEC) was
      obtained from samples of bulk tank sheep milk (62 isolates), ovine feces (4
      isolates), sheep farm environment (water, 4 isolates; air, 1 isolate), and human
      stool samples (9 isolates). The strains were considered atypical EPEC organisms,
      carrying the eae gene without harboring the pEAF plasmid. Multilocus sequence
      typing (MLST) was carried out with seven housekeeping genes and 19 sequence types
      (ST) were detected, with none of them having been previously reported for
      atypical EPEC. The most frequent ST included 41 strains isolated from milk and
      human stool samples. Genetic typing by pulsed-field gel electrophoresis (PFGE)
      resulted in 57 patterns which grouped in 24 clusters. Comparison of strains
      isolated from the different samples showed phylogenetic relationships between
      milk and human isolates and also between milk and water isolates. The results
      obtained show a possible risk for humans due to the presence of atypical EPEC in
      ewes' milk and suggest a transmission route for this emerging pathogen through
      contaminated water. 

PMID- 23872572
TI  - Combining individual-based modeling and food microenvironment descriptions to
      predict the growth of Listeria monocytogenes on smear soft cheese.
AB  - An individual-based modeling (IBM) approach was developed to describe the
      behavior of a few Listeria monocytogenes cells contaminating smear soft cheese
      surface. The IBM approach consisted of assessing the stochastic individual
      behaviors of cells on cheese surfaces and knowing the characteristics of their
      surrounding microenvironments. We used a microelectrode for pH measurements and
      micro-osmolality to assess the water activity of cheese microsamples. These
      measurements revealed a high variability of microscale pH compared to that of
      macroscale pH. A model describing the increase in pH from approximately 5.0 to
      more than 7.0 during ripening was developed. The spatial variability of the
      cheese surface characterized by an increasing pH with radius and higher pH on
      crests compared to that of hollows on cheese rind was also modeled. The
      microscale water activity ranged from approximately 0.96 to 0.98 and was stable
      during ripening. The spatial variability on cheese surfaces was low compared to
      between-cheese variability. Models describing the microscale variability of
      cheese characteristics were combined with the IBM approach to simulate the
      stochastic growth of L. monocytogenes on cheese, and these simulations were
      compared to bacterial counts obtained from irradiated cheeses artificially
      contaminated at different ripening stages. The simulated variability of L.
      monocytogenes counts with the IBM/microenvironmental approach was consistent with
      the observed one. Contrasting situations corresponding to no growth or highly
      contaminated foods could be deduced from these models. Moreover, the IBM approach
      was more effective than the traditional population/macroenvironmental approach to
      describe the actual bacterial behavior variability. 

PMID- 23872575
TI  - Experimental transmission of infectious pancreatic necrosis virus from the blue
      mussel, Mytilus edulis, to cohabitating Atlantic Salmon (Salmo salar) smolts.
AB  - Integrated multitrophic aquaculture (IMTA) reduces the environmental impacts of
      commercial aquaculture systems by combining the cultivation of fed species with
      extractive species. Shellfish play a critical role in IMTA systems by filter
      feeding particulate-bound organic nutrients. As bioaccumulating organisms,
      shellfish may also increase disease risk on farms by serving as reservoirs for
      important finfish pathogens such as infectious pancreatic necrosis virus (IPNV).
      The ability of the blue mussel (Mytilus edulis) to bioaccumulate and transmit
      IPNV to naive Atlantic salmon (Salmo salar) smolts was investigated. To determine
      the ability of mussels to filter and accumulate viable IPNV, mussels were held in
      water containing log 4.6 50% tissue culture infective dose(s) (TCID50) of the
      West Buxton strain of IPNV ml(-1). Viable IPNV was detected in the digestive
      glands (DGs) of IPNV-exposed mussels as early as 2 h postexposure. The viral load
      in mussel DG tissue significantly increased with time and reached log 5.35 +/-
      0.25 TCID50 g of DG tissue(-1) after 120 h of exposure. IPNV titers never reached
      levels that were significantly greater than that in the water. Viable IPNV was
      detected in mussel feces out to 7 days postdepuration, and the virus persisted in
      DG tissues for at least 18 days of depuration. To determine whether IPNV can be
      transmitted from mussels to Atlantic salmon, IPNV-exposed mussels were
      cohabitated with naive Atlantic salmon smolts. Transmission of IPNV did occur
      from mussels to smolts at a low frequency. The results demonstrate that a
      nonenveloped virus, such as IPNV, can accumulate in mussels and be transferred to
      naive fish. 

PMID- 23872574
TI  - Adhesion of human and animal Escherichia coli strains in association with their
      virulence-associated genes and phylogenetic origins.
AB  - Intestinal colonization is influenced by the ability of the bacterium to inhabit
      a niche, which is based on the expression of colonization factors. Escherichia
      coli carries a broad range of virulence-associated genes (VAGs) which contribute
      to intestinal (inVAGs) and extraintestinal (exVAGs) infection. Moreover, initial
      evidence indicates that inVAGs and exVAGs support intestinal colonization. We
      developed new screening tools to genotypically and phenotypically characterize E.
      coli isolates originating in humans, domestic pigs, and 17 wild mammal and avian
      species. We analyzed 317 isolates for the occurrence of 44 VAGs using a novel
      multiplex PCR microbead assay (MPMA) and for adhesion to four epithelial cell
      lines using a new adhesion assay. We correlated data for the definition of new
      adhesion genes. inVAGs were identified only sporadically, particularly in roe
      deer (Capreolus capreolus) and the European hedgehog ( Erinaceus europaeus). The
      prevalence of exVAGs depended on isolation from a specific host. Human
      uropathogenic E. coli isolates carried exVAGs with the highest prevalence,
      followed by badger (Meles meles) and roe deer isolates. Adhesion was found to be
      very diverse. Adhesion was specific to cells, host, and tissue, though it was
      also unspecific. Occurrence of the following VAGs was associated with a higher
      rate of adhesion to one or more cell lines: afa-dra, daaD, tsh, vat, ibeA, fyuA,
      mat, sfa-foc, malX, pic, irp2, and papC. In summary, we established new screening
      methods which enabled us to characterize large numbers of E. coli isolates. We
      defined reservoirs for potential pathogenic E. coli. We also identified a very
      broad range of colonization strategies and defined potential new adhesion genes. 

PMID- 23872576
TI  - Variation of the virus-related elements within syntenic genomes of the
      hyperthermophilic Archaeon Aeropyrum.
AB  - The increasing number of genome sequences of archaea and bacteria show their
      adaptation to different environmental conditions at the genomic level. Aeropyrum
      spp. are aerobic and hyperthermophilic archaea. Aeropyrum camini was isolated
      from a deep-sea hydrothermal vent, and Aeropyrum pernix was isolated from a
      coastal solfataric vent. To investigate the adaptation strategy in each habitat,
      we compared the genomes of the two species. Shared genome features were a small
      genome size, a high GC content, and a large portion of orthologous genes (86 to
      88%). The genomes also showed high synteny. These shared features may have been
      derived from the small number of mobile genetic elements and the lack of a RecBCD
      system, a recombinational enzyme complex. In addition, the specialized physiology
      (aerobic and hyperthermophilic) of Aeropyrum spp. may also contribute to the
      entire-genome similarity. Despite having stable genomes, interference of synteny
      occurred with two proviruses, A. pernix spindle-shaped virus 1 (APSV1) and A.
      pernix ovoid virus 1 (APOV1), and clustered regularly interspaced short
      palindromic repeat (CRISPR) elements. Spacer sequences derived from the A. camini
      CRISPR showed significant matches with protospacers of the two proviruses
      infecting A. pernix, indicating that A. camini interacted with viruses closely
      related to APSV1 and APOV1. Furthermore, a significant fraction of the
      nonorthologous genes (41 to 45%) were proviral genes or ORFans probably
      originating from viruses. Although the genomes of A. camini and A. pernix were
      conserved, we observed nonsynteny that was attributed primarily to virus-related
      elements. Our findings indicated that the genomic diversification of Aeropyrum
      spp. is substantially caused by viruses. 

PMID- 23872577
TI  - Diabetes during pregnancy influences Hofbauer cells, a subtype of placental
      macrophages, to acquire a pro-inflammatory phenotype.
AB  - Growing evidence indicates that maternal pathophysiological conditions, such as
      diabetes, influence fetal growth and could program metabolic disease in
      adulthood. Placental cells, particularly Hofbauer cells (HBCs), which are
      placental macrophages characterized by an anti-inflammatory profile (M2), can
      sense the modified maternal environment. The goal of this study was to
      investigate the direct effect of hyperglycemia on HBCs. We studied, at mRNA and
      protein levels, some markers of M2 and M1 (pro-inflammatory) macrophages in
      placentae from control and diabetic patients to assess the balance between pro-
      and anti-inflammatory macrophages: an imbalance of M2 to M1 macrophages has been
      observed in humans. We used pregnant rats, receiving a single injection of
      streptozotocin (STZ), as a model of maternal diabetes. We noticed a M2-to-M1
      macrophage unbalance as we observed in human. An in vitro model of isolated rat
      HBCs was used to identify the direct effects of high glucose. We found that high
      glucose stimulation activated genes belonging to TLR (Toll-Like Receptor)
      dependent inflammatory pathways. Moreover, the HBCs stimulated by high glucose
      switched their M2 profile towards M1, with increased expression of pro
      inflammatory cytokines and markers. We also noticed that the oxidative-stress
      pathway was activated in response to high glucose driven by Hif-1alpha. In this
      study, we demonstrated that diabetes/hyperglycemia affect the anti-inflammatory
      profile of HBCs, by stimulating these cells to acquire an inflammatory profile
      leading to adverse consequences for the fetal-placental-maternal axis. 

PMID- 23872579
TI  - An autonomic link between inhaled diesel exhaust and impaired cardiac
      performance: insight from treadmill and dobutamine challenges in heart failure
      prone rats.
AB  - Cardiac disease exacerbation is associated with short-term exposure to vehicular
      emissions. Diesel exhaust (DE) might impair cardiac performance in part through
      perturbing efferent sympathetic and parasympathetic autonomic nervous system
      (ANS) input to the heart. We hypothesized that acute changes in ANS balance
      mediate decreased cardiac performance upon DE inhalation. Young adult heart
      failure-prone rats were implanted with radiotelemeters to measure heart rate
      (HR), HR variability (HRV), blood pressure (BP), core body temperature, and pre
      ejection period (PEP, a contractility index). Animals pretreated with sympathetic
      antagonist (atenolol), parasympathetic antagonist (atropine), or saline were
      exposed to DE (500 ug/m(3) fine particulate matter, 4h) or filtered air and then
      treadmill exercise challenged. At 1 day postexposure, separate rats were
      catheterized for left ventricular pressure (LVP), contractility, and lusitropy
      and assessed for autonomic influence using the sympathoagonist dobutamine and
      surgical vagotomy. During DE exposure, atenolol inhibited increases in HR, BP,
      and contractility, but not body temperature, suggesting a role for sympathetic
      dominance. During treadmill recovery at 4h post-DE exposure, HR and HRV indicated
      parasympathetic dominance in saline- and atenolol-pretreated groups that atropine
      inhibited. Conversely, at treadmill recovery 21h post-DE exposure, HRV and PEP
      indicated sympathetic dominance and subsequently diminished contractility that
      only atenolol inhibited. LVP at 1 day postexposure indicated that DE impaired
      contractility and lusitropy while abolishing parasympathetic-regulated cardiac
      responses to dobutamine. This is the first evidence that air pollutant inhalation
      both causes time-dependent oscillations between sympathetic and parasympathetic
      dominance and decreases cardiac performance via aberrant sympathetic dominance. 

PMID- 23872573
TI  - Bacterial community response to petroleum hydrocarbon amendments in freshwater,
      marine, and hypersaline water-containing microcosms.
AB  - Hydrocarbon-degrading bacterial communities from freshwater, marine, and
      hypersaline Brazilian aquatic ecosystems (with water salinities corresponding to
      0.2%, 4%, and 5%, respectively) were enriched with different hydrocarbons
      (heptadecane, naphthalene, or crude oil). Changes within the different microcosms
      of bacterial communities were analyzed using cultivation approaches and molecular
      methods (DNA and RNA extraction, followed by genetic fingerprinting and analyses
      of clone libraries based on the 16S rRNA-coding gene). A redundancy analysis
      (RDA) of the genetic fingerprint data and a principal component analysis (PCA) of
      the clone libraries revealed hydrocarbon-enriched bacterial communities specific
      for each ecosystem studied. However, within the same ecosystem, different
      bacterial communities were selected according to the petroleum hydrocarbon used.
      In general, the results demonstrated that Acinetobacter and Cloacibacterium were
      the dominant genera in freshwater microcosms; the Oceanospirillales order and the
      Marinobacter, Pseudomonas, and Cycloclasticus genera predominated in marine
      microcosms; and the Oceanospirillales order and the Marinobacter genus were
      selected in the different hydrocarbon-containing microcosms in hypersaline water.
      Determination of total petroleum hydrocarbons (TPHs) in all microcosms after 32
      days of incubation showed a decrease in the hydrocarbon concentration compared to
      that for the controls. A total of 50 (41.3%) isolates from the different
      hydrocarbon-contaminated microcosms were associated with the dominant operational
      taxonomic units (OTUs) obtained from the clone libraries, and their growth in the
      hydrocarbon contaminating the microcosm from which they were isolated as the sole
      carbon source was observed. These data provide insight into the general response
      of bacterial communities from freshwater, marine, and hypersaline aquatic
      ecosystems to petroleum hydrocarbon contamination. 

PMID- 23872578
TI  - Animal models of in utero exposure to a high fat diet: a review.
AB  - The incidence of metabolic disease, including type 2 diabetes and obesity, has
      increased to epidemic levels in recent years. A growing body of evidence suggests
      that the intrauterine environment plays a key role in the development of
      metabolic disease in offspring. Among other perturbations in early life,
      alteration in the provision of nutrients has profound and lasting effects on the
      long term health and well being of offspring. Rodent and non-human primate models
      provide a means to understand the underlying mechanisms of this programming
      effect. These different models demonstrate converging effects of a maternal high
      fat diet on insulin and glucose metabolism, energy balance, cardiovascular
      function and adiposity in offspring. Furthermore, evidence suggests that the
      early life environment can result in epigenetic changes that set the stage for
      alterations in key pathways of metabolism that lead to type 2 diabetes or
      obesity. Identifying and understanding the causal factors responsible for this
      metabolic dysregulation is vital to curtailing these epidemics. This article is
      part of a Special Issue entitled: Modulation of Adipose Tissue in Health and
      Disease. 

PMID- 23872580
TI  - Macrophage solubilization and cytotoxicity of indium-containing particles in
      vitro.
AB  - Indium-containing particles (ICPs) are used extensively in the microelectronics
      industry. Pulmonary toxicity is observed after inhalation exposure to ICPs;
      however, the mechanism(s) of pathogenesis is unclear. ICPs are insoluble at
      physiological pH and are initially engulfed by alveolar macrophages (and likely
      airway epithelial cells). We hypothesized that uptake of ICPs by macrophages
      followed by phagolysosomal acidification results in the solubilization of ICPs
      into cytotoxic indium ions. To address this, we characterized the in vitro
      cytotoxicity of indium phosphide (InP) or indium tin oxide (ITO) particles with
      macrophages (RAW cells) and lung-derived epithelial (LA-4) cells at 24h using
      metabolic (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) and
      membrane integrity (lactate dehydrogenase) assays. InP and ITO were readily
      phagocytosed by RAW and LA-4 cells; however, the particles were much more
      cytotoxic to RAW cells and cytotoxicity was dose dependent. Treatment of RAW
      cells with cytochalasin D (CytoD) blocked particle phagocytosis and reduced
      cytotoxicity. Treatment of RAW cells with bafilomycin A1, a specific inhibitor of
      phagolysosomal acidification, also reduced cytotoxicity but did not block
      particle uptake. Based on direct indium measurements, the concentration of ionic
      indium was increased in culture medium from RAW but not LA-4 cells following 24-h
      treatment with particles. Ionic indium derived from RAW cells was significantly
      reduced by treatment with CytoD. These data implicate macrophage uptake and
      solubilization of InP and ITO via phagolysosomal acidification as requisite for
      particle-induced cytotoxicity and the release of indium ions. This may apply to
      other ICPs and strongly supports the notion that ICPs require solubilization in
      order to be toxic. 

PMID- 23872581
TI  - Short-term exposure to ozone does not impair vascular function or affect heart
      rate variability in healthy young men.
AB  - Air pollution exposure is associated with cardiovascular morbidity and mortality,
      yet the role of individual pollutants remains unclear. In particular, there is
      uncertainty regarding the acute effect of ozone exposure on cardiovascular
      disease. In these studies, we aimed to determine the effect of ozone exposure on
      vascular function, fibrinolysis, and the autonomic regulation of the heart.
      Thirty-six healthy men were exposed to ozone (300 ppb) and filtered air for 75min
      on two occasions in randomized double-blind crossover studies. Bilateral forearm
      blood flow (FBF) was measured using forearm venous occlusion plethysmography
      before and during intra-arterial infusions of vasodilators 2-4 and 6-8h after
      each exposure. Heart rhythm and heart rate variability (HRV) were monitored
      during and 24h after exposure. Compared with filtered air, ozone exposure did not
      alter heart rate, blood pressure, or resting FBF at either 2 or 6h. There was a
      dose-dependent increase in FBF with all vasodilators that was similar after both
      exposures at 2-4h. Ozone exposure did not impair vasomotor or fibrinolytic
      function at 6-8h but rather increased vasodilatation to acetylcholine (p = .015)
      and sodium nitroprusside (p = .005). Ozone did not affect measures of HRV during
      or after the exposure. Our findings do not support a direct rapid effect of ozone
      on vascular function or cardiac autonomic control although we cannot exclude an
      effect of chronic exposure or an interaction between ozone and alternative air
      pollutants that may be responsible for the adverse cardiovascular health effects
      attributed to ozone. 

PMID- 23872582
TI  - Utility of rat liver S9 fractions to study skin-sensitizing prohaptens in a
      modified KeratinoSens assay.
AB  - Prohaptens are chemicals, which may cause skin sensitization after being
      converted into electrophilic molecules by skin enzymes. Aroclor-induced rat liver
      S9 fractions represent the metabolic activation system most commonly used in in
      vitro toxicology. This system contains much higher enzyme activities compared
      with those reported in skin, but it may still serve as a surrogate system to
      study the potential of chemicals to act as prohaptens. To test this concept, the
      luciferase induction in KeratinoSens reporter cells treated with chemicals in
      presence and absence of S9 fractions was measured. Suspected prohaptens such as
      methyl isoeugenol, eugenol, or trans-anethole gave no, or only weak, ge ne
      induction in absence of S9 fractions, and a significantly enhanced luciferase
      induction in presence of S9, proving their prohapten status. Direct-acting
      haptens like 2,4-dinitrochlorobenzene or cinnamic aldehyde gave a reduced
      response in presence of S9. We evaluated whether this metabolic activation assay
      might be implemented in a tiered screening strategy to counter-screen negatives
      in the KeratinoSens assay to enhance sensitivity. To this aim, all chemicals
      classified negative were retested with this activation step. Among the 77
      chemicals found as correct-negatives, 73 were also negative in presence of
      metabolic activation, thus this counterscreen would reduce specificity only
      slightly. However, this comprehensive screening showed that only a small fraction
      of the known skin sensitizers need activation by the S9 system. Therefore, the
      KeratinoSens-S9 assay appears useful for the in vitro evaluation of specific
      classes of potential prohaptens and to mechanistically rationalize their
      prohapten status. 

PMID- 23872583
TI  - Erlotinib resistance in lung cancer cells mediated by integrin beta1/Src/Akt
      driven bypass signaling.
AB  - EGF receptor (EGFR) kinase inhibitors, including gefitinib and erlotinib, exert
      potent therapeutic efficacy in non-small cell lung cancers harboring EGFR
      activating mutations. However, most patients ultimately develop resistance to
      these drugs. Here, we report a novel mechanism of acquired resistance to EGFR
      tyrosine kinase inhibitors and the reversal of which could improve clinical
      outcomes. In erlotinib-resistant lung cancer cells harboring activating EGFR
      mutations that we established, there was increased expression of Src, integrin
      beta1, alpha2, and alpha5 along with enhanced cell adhesion activity.
      Interestingly, RNAi-mediated silencing of integrin beta1 restored erlotinib
      sensitivity and reduced activation of Src and Akt after erlotinib treatment.
      Furthermore, Src silencing inhibited Akt phosphorylation and cell growth, with
      this inhibitory effect further augmented by erlotinib treatment. Increased
      expression of integrin beta1, alpha5, and/or alpha2 was also observed in
      refractory tumor samples from patients with lung cancer treated with erlotinib
      and/or gefitinib. Together, our findings identify the integrin beta1/Src/Akt
      signaling pathway as a key mediator of acquired resistance to EGFR-targeted
      anticancer drugs.

PMID- 23872584
TI  - A synthetic lethality-based strategy to treat cancers harboring a genetic
      deficiency in the chromatin remodeling factor BRG1.
AB  - The occurrence of inactivating mutations in SWI/SNF chromatin-remodeling genes in
      common cancers has attracted a great deal of interest. However, mechanistic
      strategies to target tumor cells carrying such mutations are yet to be developed.
      This study proposes a synthetic-lethality therapy for treating cancers deficient
      in the SWI/SNF catalytic (ATPase) subunit, BRG1/SMARCA4. The strategy relies upon
      inhibition of BRM/SMARCA2, another catalytic SWI/SNF subunit with a BRG1-related
      activity. Immunohistochemical analysis of a cohort of non-small-cell lung
      carcinomas (NSCLC) indicated that 15.5% (16 of 103) of the cohort, corresponding
      to preferentially undifferentiated tumors, was deficient in BRG1 expression. All
      BRG1-deficient cases were negative for alterations in known therapeutic target
      genes, for example, EGFR and DDR2 gene mutations, ALK gene fusions, or FGFR1 gene
      amplifications. RNA interference (RNAi)-mediated silencing of BRM suppressed the
      growth of BRG1-deficient cancer cells relative to BRG1-proficient cancer cells,
      inducing senescence via activation of p21/CDKN1A. This growth suppression was
      reversed by transduction of wild-type but not ATPase-deficient BRG1. In support
      of these in vitro results, a conditional RNAi study conducted in vivo revealed
      that BRM depletion suppressed the growth of BRG1-deficient tumor xenografts. Our
      results offer a rationale to develop BRM-ATPase inhibitors as a strategy to treat
      BRG1/SMARCA4-deficient cancers, including NSCLCs that lack mutations in presently
      known therapeutic target genes.

PMID- 23872585
TI  - Cardiac MRI of patients with implanted electrical cardiac devices.
AB  - Implantable pulse generators and defibrillators have traditionally been
      considered contraindications to MRI. However, recent data have challenged this
      paradigm and demonstrated that patients with newer generation devices can safely
      undergo MRI, including cardiac MRI, provided basic precautions are taken. Indeed,
      the introduction of MRI conditional systems has led to a conceptual shift in
      clinical decision making-'can this patient undergo MRI safely?' is being
      superseded by 'should this patient be implanted with an MRI conditional device?'.
      This review outlines the risks associated with MRI in patients with implanted
      cardiac devices, and discusses practical measures to minimise risks and
      facilitate safe and diagnostic scanning. 

PMID- 23872586
TI  - [Not Available].

PMID- 23872587
TI  - The positive predictive value of ct-proAVP (copeptin) in patients with STEMI.

PMID- 23872588
TI  - Multiple cardiovascular risk factors in Kenya: evidence from a health and
      demographic surveillance system using the WHO STEPwise approach to chronic
      disease risk factor surveillance.
AB  - OBJECTIVE: To describe the distribution of cardiovascular risk factors in western
      Kenya using a Health and Demographic Surveillance System (HDSS). DESIGN:
      Population based survey of residents in an HDSS. SETTING: Webuye Division in
      Bungoma East District, Western Province of Kenya. PATIENTS: 4037 adults >= 18
      years of age. INTERVENTIONS: Home based survey using the WHO STEPwise approach to
      chronic disease risk factor surveillance. MAIN OUTCOME MEASURES: Self-report of
      high blood pressure, high blood sugar, tobacco use, alcohol use, physical
      activity, and fruit/vegetable intake. RESULTS: The median age of the population
      was 35 years (IQR 26-50). Less than 6% of the population reported high blood
      pressure or blood sugar. Tobacco and alcohol use were reported in 7% and 16% of
      the population, respectively. The majority of the population (93%) was physically
      active. The average number of days per week that participants reported intake of
      fruits (3.1 +/- 0.1) or vegetables (1.6 +/- 0.1) was low. In multiple logistic
      regression analyses, women were more likely to report a history of high blood
      pressure (OR 2.72, 95% CI 1.9 to 3.9), less likely to report using tobacco (OR
      0.08, 95% CI 0.06 to 0.11), less likely to report alcohol use (OR 0.18, 95% CI
      0.15 to 0.21) or eat >= 5 servings per day of fruits or vegetables (OR 0.87, 95%
      CI 0.76 to 0.99) compared to men. CONCLUSIONS: The most common cardiovascular
      risk factors in peri-urban western Kenya are tobacco use, alcohol use, and
      inadequate intake of fruits and vegetables. Our data reveal locally relevant
      subgroup differences that could inform future prevention efforts.

PMID- 23872589
TI  - Cognitive outcomes after acute coronary syndrome: a population based comparison
      with transient ischaemic attack and minor stroke.
AB  - OBJECTIVE: Acute coronary syndrome (ACS) is associated with increased risk of
      cognitive decline when compared with controls, but case:control studies are
      subject to selection bias. We therefore compared cognitive outcomes in ACS with
      transient ischaemic attack (TIA) and minor stroke, diseases with similar risk
      factor burden generally considered to be at high risk of cognitive decline.
      DESIGN: Prospective population based cohort study SETTING: Oxford Vascular Study
      (OXVASC) carried out within a defined population of 91 000 in Oxfordshire, UK.
      PATIENTS: 614 in total: 216 ACS, 182 TIA, 216 minor (non-disabling) stroke.
      OUTCOME MEASURES: Mini-Mental-State-Examination (MMSE), Telephone Interview for
      Cognitive Status-modified (TICSm), and Montreal Cognitive Assessment (MoCA) at 1
      and 5 years. RESULTS: Overall risk factor burden was similar across groups but
      ACS patients had more smoking (27% vs 14%, p<0.001) and less hypertension (45% vs
      53%, p<0.01) and atrial fibrillation (6% vs 14%, p<0.001). Cognitive outcomes
      were worse at 1 year in ACS versus TIA patients: mean+/-SD MMSE 26.6+/-2.7 vs
      27.6+/-2.5, p<0.0001; OR=2.14, 95% CI 1.11 to 4.13 for moderate/severe cognitive
      impairment (MMSE <24) with a similar trend at 5 years, and ACS outcomes were more
      similar to minor stroke. Memory and language versus frontal/executive subtests
      were relatively more impaired in ACS than TIA and minor stroke patients.
      CONCLUSIONS: Risk of cognitive impairment after ACS is similar to minor stroke
      and higher than TIA with implications for clinical practice including consent and
      adherence with medication. Differences in cognitive domain performance suggest a
      greater role for degenerative brain pathology in ACS which may be linked to
      vascular risk profile and cardiac factors.

PMID- 23872590
TI  - Dental surveillance in the adult congenital heart disease population: the
      authors' reply.

PMID- 23872591
TI  - MRI-measured regression of carotid atherosclerosis induced by statins with and
      without niacin in a randomised controlled trial: the NIA plaque study.
AB  - OBJECTIVE: To evaluate the benefit of niacin in addition to statin therapy on
      plaque regression among older individuals with established atherosclerosis.
      DESIGN: Randomised, controlled, double-blind clinical trial. SETTING: University
      outpatient center. PATIENTS: 145 patients older than 65 years, half of them older
      than 75 years of age, with established atherosclerosis were enrolled.
      INTERVENTIONS: Participants received either extended release niacin (1500 mg
      daily) or placebo in addition to statin therapy to reach their National
      Cholesterol Education Program-defined low density lipoprotein (LDL) cholesterol
      target. MAIN OUTCOME MEASURES: The primary endpoint was reduction in the wall
      volume of the internal carotid artery (ICA) measured by MRI. RESULTS: After 18
      months, high density lipoprotein cholesterol was higher with statins plus niacin
      compared with statins alone (1.6 +/- 0.4 vs 1.4 +/- 0.4 mmol/L p<0.001). Both
      groups had significant decreases in the main outcome measure of ICA wall volume,
      which regressed at 0.5%/month (SEM 0.2, p=0.004) in the statins plus placebo
      group and at 0.7%/month in the statins plus niacin group (SEM 0.2, p<0.001).
      There was no difference in the rate of regression between groups (p=0.49).
      CONCLUSIONS: Treatment with statin therapy to presently recommended LDL levels,
      with or without niacin, resulted in significant atherosclerosis reduction.

PMID- 23872592
TI  - Secondhand smoke exposure and intermittent claudication: a Scotland-wide study of
      4231 non-smokers.
AB  - OBJECTIVE: Active smoking is an important risk factor for peripheral arterial
      disease. In contrast, published evidence on the association with secondhand smoke
      (SHS) is very limited. The aim of this study was to examine the association
      between SHS exposure and intermittent claudication (IC) among middle aged non
      smokers. DESIGN: Multivariate logistic regression analyses were used to adjust
      for potential confounders. SETTING: The Scottish Health Survey, a pan-Scotland,
      representative survey of the general population. PATIENTS: We conducted a cross
      sectional study using the Scottish Health Surveys undertaken between 1998 and
      2010. Inclusion was restricted to participants aged > 45 years. MAIN OUTCOME
      MEASURES: Of the 4231 confirmed non-smokers (self-reported non-smokers with
      salivary cotinine concentrations < 15 ng/mL), 134 (3.2%) had IC based on the
      Edinburgh Claudication Questionnaire. RESULTS: There was evidence of a dose
      relationship, whereby the risk of IC increased with increasing cotinine
      concentration. Following adjustment for potential confounders, participants with
      a cotinine concentration >= 2.7 ng/mL were still significantly more likely to
      have IC (OR 1.76, 95% CI 1.04 to 3.00; p = 0.036) compared with those with a
      cotinine concentration < 0.7 ng/mL. Among non-smokers, 5.6% (95% CI -0.8% to
      11.7%) of cases of IC were attributable to cotinine concentrations >= 2.7 ng/mL
      and a further 3.6% (95% CI -6.6% to 12.8%) to cotinine concentrations of 0.7-2.6
      ng/mL. CONCLUSIONS: As with coronary heart disease and stroke, SHS exposure was
      independently associated with IC. Our findings add to the published evidence in
      support of protecting the general public from SHS exposure.

PMID- 23872593
TI  - Patent foramen ovale closure and brain ischaemic lesions.

PMID- 23872594
TI  - TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and
      regulates pain processing.
AB  - TMEM16C belongs to the TMEM16 family, which includes the Ca(2+)-activated Cl(-)
      channels TMEM16A and TMEM16B and a small-conductance, Ca(2+)-activated,
      nonselective cation channel (SCAN), TMEM16F. We found that in rat dorsal root
      ganglia (DRG) TMEM16C was expressed mainly in the IB4-positive, non-peptidergic
      nociceptors that also express the sodium-activated potassium (K(Na)) channel
      Slack. Together these channel proteins promote K(Na) channel activity and dampen
      neuronal excitability. DRG from TMEM16C knockout rats had diminished Slack
      expression, broadened action potentials and increased excitability. Moreover, the
      TMEM16C knockout rats, as well as rats with Slack knockdown by intrathecal
      injection of short interfering RNA, exhibited increased thermal and mechanical
      sensitivity. Experiments involving heterologous expression in HEK293 cells
      further showed that TMEM16C modulated the single-channel activity of Slack
      channels and increased its sodium sensitivity. Our study thus reveals that
      TMEM16C enhances K(Na) channel activity in DRG neurons and regulates the
      processing of pain messages.

PMID- 23872595
TI  - Cellular mechanisms of brain state-dependent gain modulation in visual cortex.
AB  - Visual cortical neurons fire at higher rates to visual stimuli during locomotion
      than during immobility, while maintaining orientation selectivity. The mechanisms
      underlying this change in gain are not understood. We performed whole-cell
      recordings from layer 2/3 and layer 4 visual cortical excitatory neurons and from
      parvalbumin-positive and somatostatin-positive inhibitory neurons in mice that
      were free to rest or run on a spherical treadmill. We found that the membrane
      potential of all cell types became more depolarized and (with the exception of
      somatostatin-positive interneurons) less variable during locomotion. Cholinergic
      input was essential for maintaining the unimodal membrane potential distribution
      during immobility, whereas noradrenergic input was necessary for the tonic
      depolarization associated with locomotion. Our results provide a mechanism for
      how neuromodulation controls the gain and signal-to-noise ratio of visual
      cortical neurons during changes in the state of vigilance. 

PMID- 23872596
TI  - Fear-enhancing effects of septal oxytocin receptors.
AB  - The nonapeptide oxytocin is considered beneficial to mental health due to its
      anxiolytic, prosocial and antistress effects, but evidence for anxiogenic actions
      of oxytocin in humans has recently emerged. Using region-specific manipulations
      of the mouse oxytocin receptor (Oxtr) gene (Oxtr), we identified the lateral
      septum as the brain region mediating fear-enhancing effects of Oxtr. These
      effects emerge after social defeat and require Oxtr specifically coupled to the
      extracellular signal-regulated protein kinase pathway. 

PMID- 23872597
TI  - TARP gamma-7 selectively enhances synaptic expression of calcium-permeable
      AMPARs.
AB  - Regulation of calcium-permeable AMPA receptors (CP-AMPARs) is crucial in normal
      synaptic function and neurological disease states. Although transmembrane AMPAR
      regulatory proteins (TARPs) such as stargazin (gamma-2) modulate the properties
      of calcium-impermeable AMPARs (CI-AMPARs) and promote their synaptic targeting,
      the TARP-specific rules governing CP-AMPAR synaptic trafficking remain unclear.
      We used RNA interference to manipulate AMPAR-subunit and TARP expression in gamma
      2-lacking stargazer cerebellar granule cells--the classic model of TARP
      deficiency. We found that TARP gamma-7 selectively enhanced the synaptic
      expression of CP-AMPARs and suppressed CI-AMPARs, identifying a pivotal role of
      gamma-7 in regulating the prevalence of CP-AMPARs. In the absence of associated
      TARPs, both CP-AMPARs and CI-AMPARs were able to localize to synapses and mediate
      transmission, although their properties were altered. Our results also establish
      that TARPed synaptic receptors in granule cells require both gamma-2 and gamma-7
      and reveal an unexpected basis for the loss of AMPAR-mediated transmission in
      stargazer mice.

PMID- 23872598
TI  - Synergistic binding of transcription factors to cell-specific enhancers programs
      motor neuron identity.
AB  - Efficient transcriptional programming promises to open new frontiers in
      regenerative medicine. However, mechanisms by which programming factors transform
      cell fate are unknown, preventing more rational selection of factors to generate
      desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were
      sufficient to program rapidly and efficiently spinal motor neuron identity when
      expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by
      Phox2a led to specification of cranial, rather than spinal, motor neurons.
      Chromatin immunoprecipitation-sequencing analysis of Isl1, Lhx3 and Phox2a
      binding sites revealed that the two cell fates were programmed by the recruitment
      of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations
      characterized by a unique grammar of homeodomain binding motifs. Our findings
      suggest that synergistic interactions among transcription factors determine the
      specificity of their recruitment to cell type-specific binding sites and
      illustrate how a single transcription factor can be repurposed to program
      different cell types. 

PMID- 23872599
TI  - M2 microglia and macrophages drive oligodendrocyte differentiation during CNS
      remyelination.
AB  - The lack of therapies for progressive multiple sclerosis highlights the need to
      understand the regenerative process of remyelination that can follow CNS
      demyelination. This involves an innate immune response consisting of microglia
      and macrophages, which can be polarized to distinct functional phenotypes: pro
      inflammatory (M1) and anti-inflammatory or immunoregulatory (M2). We found that a
      switch from an M1- to an M2-dominant response occurred in microglia and
      peripherally derived macrophages as remyelination started. Oligodendrocyte
      differentiation was enhanced in vitro with M2 cell conditioned media and impaired
      in vivo following intra-lesional M2 cell depletion. M2 cell densities were
      increased in lesions of aged mice in which remyelination was enhanced by
      parabiotic coupling to a younger mouse and in multiple sclerosis lesions that
      normally show remyelination. Blocking M2 cell-derived activin-A inhibited
      oligodendrocyte differentiation during remyelination in cerebellar slice
      cultures. Thus, our results indicate that M2 cell polarization is essential for
      efficient remyelination and identify activin-A as a therapeutic target for CNS
      regeneration. 

PMID- 23872600
TI  - The influence of the pleiotropic action of erythropoietin and its derivatives on
      nephroprotection.
AB  - Erythropoietin (EPO) is traditionally described as a hematopoietic cytokine or
      growth hormone regulating proliferation, differentiation, and survival of
      erythroid progenitors. The use of EPO in patients with chronic kidney disease
      (CKD) was a milestone achievement in the treatment of anemia. However, EPO
      involves some degree of risk, which increases with increasing hemoglobin levels.
      A growing number of studies have assessed the renoprotective effects of EPO in
      acute kidney injury (AKI) or CKD. Analysis of the biological effects of
      erythropoietin and pathophysiology of CKD in these studies suggests that
      treatment with erythropoiesis-stimulating agents (ESAs) may exert renoprotection
      by pleiotropic actions on several targets and directly or indirectly slow the
      progression of CKD. By reducing ischemia and oxidative stress or strengthening
      anti-apoptotic processes, EPO may prevent the development of interstitial
      fibrosis and the destruction of tubular cells. Furthermore, it could have a
      direct protective impact on the integrity of the interstitial capillary network
      through its effects on endothelial cells and promotion of vascular repair, or
      modulate inflammation response. Thus, it is biologically plausible to suggest
      that correcting anemia with ESAs could slow the progression of CKD. The aim of
      this article is to discuss these possible renoprotection mechanisms and provide a
      comprehensive overview of erythropoietin and its derivatives. 

PMID- 23872601
TI  - Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: on-treatment
      kinetics of HBsAg serum levels vary by HBV genotype.
AB  - BACKGROUND & AIMS: We investigated whether HBV genotype influences on-treatment
      HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term
      virological response in HBeAg-negative chronic hepatitis B patients treated with
      peginterferon alfa-2a+/-lamivudine in the Phase III trial. METHODS: All patients
      (n=230) who participated in long-term follow-up were included according to the
      availability of HBsAg level measurements. Long-term virological response was
      defined as HBV DNA <= 10,000cp/ml (1786IU/ml) at 5 years post-treatment. Genotype
      specific end-of-treatment HBsAg levels associated with long-term virological
      response (identified by ROC analysis) were assessed in 199 patients with HBsAg
      measurements available at baseline and end-of-treatment. HBsAg kinetics according
      to genotype and long-term virological response were investigated in the 117
      patients with additional samples available at weeks 12, 24, and 72. RESULTS:
      Baseline HBsAg levels were significantly higher for A than B, C, and D genotypes
      (p<0.05). On-treatment HBsAg kinetics varied according to HBV genotype. The
      difference between responders and non-responders was greatest for genotype A from
      weeks 12-24; for genotypes B and D from baseline to week 12; there was no
      significant difference over any timeframe for genotype C. High positive
      predictive values for long-term virological response could be obtained by
      applying end-of-treatment genotype-specific cut-offs: 75%, 47%, 71%, and 75% for
      genotypes A (<400IU/ml), B (<50IU/ml), C (<75IU/ml), and D (<1000IU/ml),
      respectively. CONCLUSIONS: On-treatment HBsAg kinetics vary between HBV
      genotypes. Genotype-specific monitoring timeframes and end-of-treatment
      thresholds could ameliorate response-guided treatment of HBeAg-negative chronic
      hepatitis B.

PMID- 23872602
TI  - Common genetic variants regulating ADD3 gene expression alter biliary atresia
      risk.
AB  - BACKGROUND & AIMS: Biliary atresia (BA) is a rare and most severe cholestatic
      disease in neonates, but the pathogenic mechanisms are unknown. Through a
      previous genome wide association study (GWAS) on Han Chinese, we discovered
      association of the 10q24.2 region encompassing ADD3 and XPNPEP1 genes, which was
      replicated in Chinese and Thai populations. This study aims to fully characterize
      the genetic architecture at 10q24.2 and to reveal the link between the genetic
      variants and BA. METHODS: We genotyped 107 single nucleotide polymorphisms (SNPs)
      in 10q24.2 in 339 Han Chinese patients and 401 matched controls using Sequenom.
      Exhaustive follow-up studies of the association signals were performed. RESULTS:
      The combined BA-association p-value of the GWAS SNP (rs17095355) achieved
      6.06*10(-10). Further, we revealed the common risk haplotype encompassing 5
      tagging-SNPs, capturing the risk-predisposing alleles in 10q24.2 [p=5.32*10(-11);
      odds ratio, OR: 2.38; confidence interval, CI: (2.14-2.62)]. Through Sanger
      sequencing, no deleterious rare variants (RVs) residing in the risk haplotype
      were found, dismissing the theory of "synthetic" association. Moreover, in
      bioinformatics and in vivo genotype-expression investigations, the BA-associated
      potentially regulatory SNPs correlated with ADD3 gene expression (n=36;
      p=0.0030). Remarkably, the risk haplotype frequency coincides with BA incidences
      in the population, and, positive selection (favoring the derived alleles that
      arose from mutations) was evident at the ADD3 locus, suggesting a possible role
      for the BA-associated common variants in shaping the general population
      diversity. CONCLUSIONS: Common genetic variants in 10q24.2 can alter BA risk by
      regulating ADD3 expression levels in the liver, and may exert an effect on
      disease epidemiology and on the general population.

PMID- 23872603
TI  - Carbamazepine promotes liver regeneration and survival in mice.
AB  - BACKGROUND & AIMS: Carbamazepine (CBZ), a widely used anticonvulsant and mood
      stabilizer, activates multiple proliferative and pro-survival pathways. Here, we
      hypothesize that CBZ may promote hepatocellular proliferation and ameliorate
      liver regeneration. METHODS: C57BL6/J mice were orally administered CBZ or
      vehicle and underwent a 70% partial hepatectomy (PHx), 85% PHx or treatment with
      carbon tetrachloride (CCl4). Liver regeneration was determined by liver to body
      weight ratio, hepatocyte proliferation markers, and activation of intracellular
      signalling pathways. RESULTS: Two to 5days after the 70% PHx, the liver to body
      weight ratio was significantly higher in the CBZ-treated mice than in the vehicle
      treated mice. CBZ treatment upregulated the number of proliferative hepatocytes
      following PHx or CCl4 treatment, as assessed by intrahepatic Ki-67 staining, BrdU
      uptake, and PCNA protein expression. PHx surgery induced the expression of
      several cyclins and activated Akt/mTOR signalling pathways, all of which were
      enhanced by CBZ treatment. The administration of the mTOR inhibitor temsirolimus
      abrogated the hepato-proliferative effect of CBZ. CBZ treatment significantly
      improved the survival rate of the mice that underwent lethal 85% massive
      hepatectomy. CONCLUSIONS: CBZ demonstrated a novel hepato-proliferative effect
      through the activation of the mTOR signalling pathway in hepatectomised mice. CBZ
      has the potential to be a therapeutic option for facilitating efficient liver
      regeneration in patients subjected to liver surgery.

PMID- 23872604
TI  - Rat hepatocyte culture model of macrosteatosis: effect of macrosteatosis
      induction and reversal on viability and liver-specific function.
AB  - BACKGROUND & AIMS: A common cause of liver donor ineligibility is macrosteatosis.
      Recovery of such livers could enhance donor availability. Living donor studies
      have shown diet-induced reduction of macrosteatosis enables transplantation.
      However, cadaveric liver macrosteatotic reduction must be performed ex vivo
      within hours. Towards this goal, we investigated the effect of accelerated
      macrosteatosis reduction on hepatocyte viability and function using a novel
      system of macrosteatotic hepatocytes. METHODS: Hepatocytes isolated from lean
      Zucker rats were cultured in a collagen sandwich, incubated for 6 days in fatty
      acid-supplemented medium to induce steatosis, and then switched for 2 days to
      medium supplemented with lipid metabolism promoting agents. Intracellular lipid
      droplet size distribution and triglyceride, viability, albumin and urea
      secretion, and bile canalicular function were measured. RESULTS: Fatty acid
      supplemented medium induced microsteatosis in 3 days and macrosteatosis in 6
      days, the latter evidenced by large lipid droplets dislocating the nucleus to the
      cell periphery. Macrosteatosis significantly impaired all functions tested.
      Macrosteatosis decreased upon returning hepatocytes to standard medium, and the
      rate of decrease was 4-fold faster with supplemented agents, yielding 80%
      reduction in 2 days. Viability of macrosteatosis reduced hepatocytes was similar
      to control lean cells. Accelerated macrosteatotic reduction led to faster
      recovery of urea secretion and bile canalicular function, but not of albumin
      secretion. CONCLUSIONS: Macrosteatosis reversibly decreases hepatocyte function
      and supplementary agents accelerate macrosteatosis reduction and some functional
      restoration with no effect on viability. This in vitro model may be useful to
      screen agents for macrosteatotic reduction in livers before transplantation.

PMID- 23872605
TI  - Effects of intravenous albumin in patients with cirrhosis and episodic hepatic
      encephalopathy: a randomized double-blind study.
AB  - BACKGROUND & AIMS: Episodic hepatic encephalopathy is frequently precipitated by
      factors that induce circulatory dysfunction, cause oxidative stress-mediated
      damage or enhance astrocyte swelling. The administration of albumin could modify
      these factors and improve the outcome of hepatic encephalopathy. The aim of this
      study is to assess the efficacy of albumin in a multicenter, prospective, double
      blind, controlled trial (ClinicalTrials.gov number, NCT00886925). METHODS:
      Cirrhotic patients with an acute episode of hepatic encephalopathy (grade II-IV)
      were randomized to receive albumin (1.5g/kg on day 1 and 1.0g/kg on day 3) or
      isotonic saline, in addition to the usual treatment (laxatives, rifaximin 1200mg
      per day). The primary end point was the proportion of patients in which
      encephalopathy was resolved on day 4. The secondary end points included survival,
      length of hospital stay, and biochemical parameters. RESULTS: Fifty-six patients
      were randomly assigned to albumin (n=26) or saline (n=30) stratified by the
      severity of HE. Both groups were comparable regarding to demographic data, liver
      function, and precipitating factors. The percentage of patients without hepatic
      encephalopathy at day 4 did not differ between both groups (albumin: 57.7% vs.
      saline: 53.3%; p>0.05). However, significant differences in survival were found
      at day 90 (albumin: 69.2% vs. saline: 40.0%; p=0.02). CONCLUSIONS: Albumin does
      not improve the resolution of hepatic encephalopathy during hospitalization.
      However, differences in survival after hospitalization suggest that the
      development of encephalopathy may identify a subgroup of patients with advanced
      cirrhosis that may benefit from the administration of albumin.

PMID- 23872606
TI  - The Roles of Moonlighting Proteins in Bacteria.
AB  - Moonlighting proteins, characterized by their multiple autonomous functions, have
      been detected in bacteria. Surprisingly, many of these proteins are conserved and
      involved in metabolic pathway or the cell stress response. They localise to the
      bacterial surface to take on additional activities, which have been hypothesised
      to contribute to bacterial virulence or bacterial benefit. In this review, we
      compare the functions of moonlighting proteins in bacteria, describe the
      structural basis of moonlighting functions, and summarise the regulation of
      secretion and localisation of moonlighting proteins. 

PMID- 23872608
TI  - Quantum confinement-induced tunable exciton states in graphene oxide.
AB  - Graphene oxide has recently been considered to be a potential replacement for
      cadmium-based quantum dots due to its expected high fluorescence. Although
      previously reported, the origin of the luminescence in graphene oxide is still
      controversial. Here, we report the presence of core/valence excitons in graphene
      based materials, a basic ingredient for optical devices, induced by quantum
      confinement. Electron confinement in the unreacted graphitic regions of graphene
      oxide was probed by high resolution X-ray absorption near edge structure
      spectroscopy and first-principles calculations. Using experiments and
      simulations, we were able to tune the core/valence exciton energy by manipulating
      the size of graphitic regions through the degree of oxidation. The binding energy
      of an exciton in highly oxidized graphene oxide is similar to that in organic
      electroluminescent materials. These results open the possibility of graphene
      oxide-based optoelectronic device technology. 

PMID- 23872609
TI  - Synergizing nucleic acid aptamers with 1-dimensional nanostructures as label-free
      field-effect transistor biosensors.
AB  - Since the introduction by Gold et al. in 1990, nucleic acid aptamers had evolved
      to become a true contender in biosensors for protein and cell detections.
      Aptamers are short strands of synthetically designed DNA or RNA oligonucleotides
      that can be self-assembled into unique 3-dimensional structures and can bind to
      different proteins, cells or even small molecules at a high level of specificity
      and affinity. In recent years, there had been many reports in literature in using
      aptamers in place of conventional antibodies as capture biomolecules on the
      surface. This is mainly due to the better thermal stability properties and ease
      in production. Consequently, also these characteristics allowed the aptamers to
      find use in field effect transistors (FETs) based upon 1D nanostructured (1D-NS)
      as label-free biosensing. In terms of designing label-free platforms for
      biosensors applications, 1D-NS FET had been an attractive option due to reported
      high sensitivities toward protein targets arising from the large surface area for
      detection as well as to their label-free nature. Since the first aptamer-based 1D
      NS FET biosensor had surfaced in 2005, there had been many more improvements in
      the overall design and sensitivity in recent years. In this review, the latest
      developments in synergizing these two interesting areas of research (aptamers and
      1D-NS FET) will be discussed for a range of different nanowire types as well as
      for the detection results. 

PMID- 23872610
TI  - An ultrasensitive electrochemiluminescence immunoassay based on supersandwich DNA
      structure amplification with histidine as a co-reactant.
AB  - Here we report a novel electrochemiluminescence (ECL) immunosensor for
      ultrasensitive detection of carcinoembryonic antigen (CEA) via histidine labeled
      supersandwich DNA structure to amplify the ECL signal. Histidine is an alpha
      amino acid with an imidazole group, which can act as a co-reactant of tris(2,2'
      bipyridyl) ruthenium(II) (Ru(bpy)3(2+)) to amplify ECL signal. To the best of our
      knowledge, this is the first time to use histidine as co-reactant of Ru(bpy)3(2+)
      for signal amplification. The ECL substrate is fabricated by locating the complex
      of Pt nanoparticles (PtNPs) and Ru(bpy)3(2+) (Ru-PtNPs) on Nafion modified
      electrode surface. In the presence of antigens, the sandwiched immunocomplex can
      be formed between the primary antibodies on the ECL substrate and the secondary
      antibodies on the gold nanoparticles. The carried auxiliary probe I trigger a
      cascade of hybridization events between alternating auxiliary probe I and
      histidine-modified auxiliary probe II to form the long DNA concatamers. Thus the
      long DNA concatamers contain multiple histidine-modified auxiliary probe II,
      which accordingly achieve significant signal amplification. As a result, the
      sensitivity of proposed immunosensor for CEA detection is improved, the linear
      range is from 0.1 pg mL(-1) to 100 ng mL(-1) with a low detection limit of 33.3
      fg mL(-1). Moreover, with the satisfying stability, selectivity and
      reproducibility, the proposed supersandwich immunoassay performs good promise in
      clinical detection.

PMID- 23872612
TI  - Prevention of mother-to-child HIV transmission: can we meet the goal of global
      elimination of new pediatric infections?

PMID- 23872611
TI  - Prevention of mother-to-child HIV transmission within the continuum of maternal,
      newborn, and child health services.
AB  - PURPOSE OF REVIEW: To reach virtual elimination of pediatric HIV, programs for
      the prevention of mother-to-child HIV transmission (PMTCT) must expand coverage
      and achieve long-term retention of mothers and infants. Although PMTCT have been
      traditionally aligned with maternal, newborn, and child health (MNCH) services,
      novel approaches are needed to address the increasing demands of evolving global
      PMTCT policies. RECENT FINDINGS: PMTCT-MNCH integration has improved the uptake
      and timely initiation of antiretroviral therapy (ART) among treatment-eligible
      pregnant women in public health settings. Postpartum engagement of HIV-infected
      mothers and HIV-exposed infants has been insufficient, although alignment of
      visits to the childhood immunization schedule and establishment of integrated
      mother-infant clinics may increase retention. Evidence also suggests that the
      integration of maternal HIV testing into childhood immunization clinics can
      significantly increase the identification of at-risk HIV-exposed infants
      previously missed by traditional PMTCT models. SUMMARY: Targeted service
      integration models can improve PMTCT uptake. However, as global PMTCT policy
      shifts to universal provision of maternal ART during pregnancy (i.e., Option
      B/B+), these findings must be reexamined in the context of increased service
      demand and systems burden. Intensive evaluation is needed to ensure quality
      clinical care is maintained both for PMTCT and for underpinning MNCH services.

PMID- 23872613
TI  - New clinical trial designs for HIV vaccine evaluation.
AB  - PURPOSE OF REVIEW: With multiple HIV vaccine candidates suitable for efficacy
      evaluation in a rapidly changing HIV prevention landscape, innovative HIV vaccine
      trial design research is much needed to optimally utilize resources by building
      on lessons learned from past HIV vaccine efficacy trials. RECENT FINDINGS:
      Several recent articles propose new vaccine efficacy trial design strategies
      tailored to the emerging needs in HIV vaccine evaluation. These include a focus
      on efficacy evaluation proximal to the vaccination series; more intensive interim
      monitoring for potential harm, nonefficacy and high efficacy of the vaccine;
      simultaneous evaluation of multiple vaccine regimens with a shared placebo group;
      designs that include pilot immunogenicity studies of putative immune correlates
      to expedite their evaluation; as well as designs tailored to evaluate vaccine
      efficacy in the context of partially effective nonvaccine prevention modalities.
      SUMMARY: A more rapid evaluation of multiple vaccine candidates is possible.
      Weaker vaccines can be weeded out quickly. Pilot studies can be done during the
      trial to prepare for a timely immune correlates assessment. Evidence that emerges
      regarding the efficacy of nonvaccine prevention modalities will have important
      implications for future trial designs.

PMID- 23872607
TI  - Autonomic cardiac innervation: development and adult plasticity.
AB  - Autonomic cardiac neurons have a common origin in the neural crest but undergo
      distinct developmental differentiation as they mature toward their adult
      phenotype. Progenitor cells respond to repulsive cues during migration, followed
      by differentiation cues from paracrine sources that promote neurochemistry and
      differentiation. When autonomic axons start to innervate cardiac tissue,
      neurotrophic factors from vascular tissue are essential for maintenance of
      neurons before they reach their targets, upon which target-derived trophic
      factors take over final maturation, synaptic strength and postnatal survival.
      Although target-derived neurotrophins have a central role to play in development,
      alternative sources of neurotrophins may also modulate innervation. Both
      developing and adult sympathetic neurons express proNGF, and adult
      parasympathetic cardiac ganglion neurons also synthesize and release NGF. The
      physiological function of these "non-classical" cardiac sources of neurotrophins
      remains to be determined, especially in relation to autocrine/paracrine
      sustenance during development.   Cardiac autonomic nerves are closely spatially
      associated in cardiac plexuses, ganglia and pacemaker regions and so are
      sensitive to release of neurotransmitter, neuropeptides and trophic factors from
      adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within
      the two arms of the autonomic system that is critical for disease progression.
      Although this crosstalk between sympathetic and parasympathetic nerves has been
      well established for adult nerves, it is unclear whether a degree of paracrine
      regulation occurs across the autonomic limbs during development. Aberrant nerve
      remodeling is a common occurrence in many adult cardiovascular pathologies, and
      the mechanisms regulating outgrowth or denervation are disparate. However,
      autonomic neurons display considerable plasticity in this regard with
      neurotrophins and inflammatory cytokines having a central regulatory function,
      including in possible neurotransmitter changes. Certainly, neurotrophins and
      cytokines regulate transcriptional factors in adult autonomic neurons that have
      vital differentiation roles in development. Particularly for parasympathetic
      cardiac ganglion neurons, additional examinations of developmental regulatory
      mechanisms will potentially aid in understanding attenuated parasympathetic
      function in a number of conditions, including heart failure. 

PMID- 23872615
TI  - Detection of antibody to Purpureocillium lilacinum by immunofluorescent assay and
      flow cytometry in serum of infected C57BL/6 mice.
AB  - Purpureocillium lilacinum is an emerging pathogenic fungus that can cause
      different clinical manifestations ranging from cutaneous and sub-cutaneous
      infections to severe oculomycosis. In this study, using both conventional
      indirect immunofluorescence and non-conventional flow cytometry approaches, IgG
      antibodies were readily detected in both C57BL/6 immunocompetent and
      immunosuppressed mice after i.v. infection with P. lilacinum. The humoral immune
      response was specific, since virtually no antibodies were detected in the serum
      of control mice. Flow cytometry assays also showed both quantitative and
      qualitative differences in total IgG and its isotypes in sera of immunocompetent
      and immunosupressed infected mice. Although a good starting point, it is clear
      that the effectiveness of serological assays for P. lilacinum hyalohyphomycosis
      identification in clinical studies still requires further standardization. Upon
      further validation in humans, these techniques have the potential to be suitable
      to detect P. lilacinum infection in patients, thereby avoiding current laborious
      and time-consuming culture techniques. 

PMID- 23872614
TI  - Multi-platform genotoxicity analysis of silver nanoparticles in the model cell
      line CHO-K1.
AB  - Investigation of the genotoxic potential of nanomaterials is essential to
      evaluate if they pose a cancer risk for exposed workers and consumers. The
      Chinese hamster ovary cell line CHO-K1 is recommended by the OECD for use in the
      micronucleus assay and is commonly used for genotoxicity testing. However,
      studies investigating if this cell line is suitable for the genotoxic evaluation
      of nanomaterials, including induction of DNA adduct and micronuclei formation,
      are rare and for silver nanoparticles (Ag NPs) missing. Therefore, we here
      systematically investigated DNA and chromosomal damage induced by BSA coated Ag
      NPs (15.9+/-7.6 nm) in CHO-K1 cells in relation to cellular uptake and
      intracellular localization, their effects on mitochondrial activity and
      production of reactive oxygen species (ROS), cell cycle, apoptosis and necrosis.
      Ag NPs are taken up by CHO-K1 cells and are presumably translocated into
      endosomes/lysosomes. Our cytotoxicity studies demonstrated a concentration
      dependent decrease of mitochondrial activity and increase of intracellular
      reactive oxygen species (ROS) in CHO-K1 cells following exposure to Ag NPs and
      Ag+ (0-20 MUg/ml) for 24h. Annexin V/propidium iodide assay showed that Ag NPs
      and Ag+ induced apoptosis and necrosis, which is in agreement with an increased
      fraction of cells in subG1 phase of the cell cycle. Genotoxicity studies showed
      that Ag NPs but also silver ions (Ag+) induced bulky-DNA adducts, 8-oxodG and
      micronuclei formation in a concentration-dependent manner, however, there were
      quantitative and qualitative differences between the particulate and ionic form
      of silver. Taken together, our multi-platform genotoxicity and cytotoxicity
      analysis demonstrates that CHO-K1 cells are suitable for the investigation of
      genotoxicity of nanoparticles like Ag NPs.

PMID- 23872616
TI  - A reversible ratiometric sensor for intracellular Cu2+ imaging: metal
      coordination-altered FRET in a dual fluorophore hybrid.
AB  - ICT fluorophore benzoxadiazole with its electron-donating group modified as a
      Cu(2+) chelator was conjugated with coumarin to construct a new ratiometric
      sensor with reversible intracellular Cu(2+) imaging ability. 

PMID- 23872617
TI  - Distinct detoxification mechanisms confer resistance to mesotrione and atrazine
      in a population of waterhemp.
AB  - Previous research reported the first case of resistance to mesotrione and other 4
      hydroxyphenylpyruvate dioxygenase (HPPD) herbicides in a waterhemp (Amaranthus
      tuberculatus) population designated MCR (for McLean County mesotrione- and
      atrazine-resistant). Herein, experiments were conducted to determine if target
      site or nontarget site mechanisms confer mesotrione resistance in MCR.
      Additionally, the basis for atrazine resistance was investigated in MCR and an
      atrazine-resistant but mesotrione-sensitive population (ACR for Adams County
      mesotrione-sensitive but atrazine-resistant). A standard sensitive population
      (WCS for Wayne County herbicide-sensitive) was also used for comparison.
      Mesotrione resistance was not due to an alteration in HPPD sequence, HPPD
      expression, or reduced herbicide absorption. Metabolism studies using whole
      plants and excised leaves revealed that the time for 50% of absorbed mesotrione
      to degrade in MCR was significantly shorter than in ACR and WCS, which correlated
      with previous phenotypic responses to mesotrione and the quantity of the
      metabolite 4-hydroxy-mesotrione in excised leaves. The cytochrome P450
      monooxygenase inhibitors malathion and tetcyclacis significantly reduced
      mesotrione metabolism in MCR and corn (Zea mays) excised leaves but not in ACR.
      Furthermore, malathion increased mesotrione activity in MCR seedlings in
      greenhouse studies. These results indicate that enhanced oxidative metabolism
      contributes significantly to mesotrione resistance in MCR. Sequence analysis of
      atrazine-resistant (MCR and ACR) and atrazine-sensitive (WCS) waterhemp
      populations detected no differences in the psbA gene. The times for 50% of
      absorbed atrazine to degrade in corn, MCR, and ACR leaves were shorter than in
      WCS, and a polar metabolite of atrazine was detected in corn, MCR, and ACR that
      cochromatographed with a synthetic atrazine-glutathione conjugate. Thus, elevated
      rates of metabolism via distinct detoxification mechanisms contribute to
      mesotrione and atrazine resistance within the MCR population. 

PMID- 23872618
TI  - Radiosurgery for the treatment of psychiatric disorders: a review.
AB  - Radiosurgery for psychiatric disorders has been performed for more than 50 years.
      The use of deep brain stimulation has recently been expanded to the
      investigational treatment of specific psychiatric disorders. A literature review
      of past studies incorporating radiosurgical stereotactic lesions for psychiatric
      disorders was performed to provide historic context and possible guidance for
      current and future attempts at treating psychiatric disorders, especially by
      gamma capsulotomy. The anatomic target localization, dose selection, and the
      outcome of the radiosurgical procedures were reviewed, and the evolutions of
      lesioning strategies were analyzed with particular emphasis on the dose
      selection. Large-scale prospective studies with strict inclusion and well
      defined, objective outcome criteria are necessary for defining the role of
      radiosurgery for the treatment of psychiatric disorders. 

PMID- 23872619
TI  - Association between glaucoma, glaucoma therapies, and erectile dysfunction.
AB  - PURPOSE: To examine the association between (1) glaucoma and erectile dysfunction
      (ED) and (2) topical beta-blocker (BB) use and ED. METHODS: A comprehensive,
      province-wide database of physician visits and diagnoses and prescription drug
      dispensing was used to identify cases of ED (1380) and find corresponding
      controls (13,800). A conditional logistic regression model was used to estimate
      rate ratios for 2 main exposures: (1) diagnosis of glaucoma and (2) use of a
      prescription of a topical BB before the index date. A variety of risk factors
      were adjusted for. RESULTS: Cases were more likely to have coronary artery
      disease, chronic obstructive pulmonary disease, and diabetes. A crude rate ratio
      of the current diagnosis of ED in a population with at least 2 separate diagnoses
      of glaucoma was 1.34 and when adjusted for a number of variables (including oral
      BB use), this ratio was 1.37 [95% confidence interval (CI), 1.06-1.76]. Use of
      topical BB in the 30 days before the diagnosis of ED did not have a significant
      association with a diagnosis of ED, with crude and adjusted rate ratios of 1.05
      and 1.10, respectively (95% CI, 0.61-1.99). Topical ocular prostaglandin use was
      also not associated with ED, with crude and adjusted rate ratios of 0.96 and
      0.93, respectively (95% CI, 0.57-1.53). CONCLUSIONS: Our results confirmed an
      association between ED and glaucoma that cannot be attributed to topical BB use.
      Given that most cardiovascular and metabolic risk factors were adjusted for,
      further research in this area will be necessary to elucidate the nature of this
      association and potential causation.

PMID- 23872620
TI  - Inadvertent filtering bleb due to corneal stromal wick syndrome.
AB  - We report a unique case in which an inadvertent filtering bleb was created after
      a complicated cataract surgery through an unusual mechanism: an internal fragment
      of corneal stroma, which was still attached at one end of the clear corneal
      wound, was pushed into the anterior chamber, became inadvertently entrapped in
      the wound, and served as a wick to prevent complete healing. 

PMID- 23872621
TI  - Anterior lens capsule application in phacotrabeculectomy.

PMID- 23872623
TI  - Vibronic coupling density analysis for the chain-length dependence of
      reorganization energies in oligofluorenes: a comparative study with
      oligothiophenes.
AB  - The vibronic coupling constants and reorganization energies of oligofluorenes
      OF(n) (n = 1-6) are calculated for their cationic states (hole transport). Those
      of oligothiophenes OT(2n) (n = 1-6) are also calculated for comparison. The
      vibronic coupling constants of OF(n) are smaller than those of OT(2n), and
      decrease with increasing n. For the elucidation of the small vibronic couplings
      of the oligofluorenes, the calculated vibronic coupling constants are analyzed on
      the basis of the concept of vibronic coupling density. The vibronic coupling
      density of OF(n) becomes small in the middle of the chain with increasing n
      because of the reduction in the electron-density difference between the neutral
      and cationic states. It is found that orbital relaxation plays a crucial role in
      the distribution of the electron-density difference. From the fragment molecular
      orbital analyses, the large orbital relaxation in OF(n) is found to originate
      from the small transfer integral between the fragment molecular orbitals. These
      findings led to a design principle for a carrier-transporting oligomer/polymer
      with small vibronic couplings, or small reorganization energy, as follows: the
      orbital interaction between the monomers should be small from the view of
      vibronic couplings. 

PMID- 23872624
TI  - A spin-crossover ionic liquid from the cationic iron(III) Schiff base complex.
AB  - A thermochromic magnetic ionic liquid containing a cationic iron(III) Schiff-base
      complex has been developed, whose color and magnetic moment change with
      temperature because of spin crossover in the liquid state. This spin-crossover
      behavior closely resembles that of a solid having the same cation.

PMID- 23872622
TI  - Na+/H+ exchanger inhibitor augments hyperosmolarity-induced vasoconstriction by
      enhancing actin polymerization.
AB  - Vascular smooth muscle cells (VSMCs) exhibit shrinkage-induced activation of
      Na(+)/H(+) exchanger isoform 1 (NHE-1) and Na(+), K(+), 2Cl(-) cotransporter
      (NKCC) under hyperosmotic conditions. To investigate the roles of these ion
      transporters in vascular smooth muscle force induced by hyperosmotic stress, we
      tested the effects of 5-(N, N-dimethyl)-amiloride (DMA; NHE inhibitor),
      cariporide (a selective NHE-1 inhibitor), and bumetanide (NKCC inhibitor) on the
      contractile response of rat aortic rings to hyperosmolar solutions. NHE
      inhibitors significantly augmented the maximum force response and contractile
      sensitivity to hyperosmolar sucrose, NaCl, and glucose in endothelium-denuded
      rings. Bumetanide elicited a comparatively modest increase in sensitivity. NHE
      inhibitors blocked the increase in intracellular pH and enhanced the cell volume
      decrease of cultured VSMCs after exposure to hyperosmolar sucrose. However, DMA
      had no effect on the increase in cytosolic free Ca(2+) concentration ([Ca(2+)]i)
      in rat VSMCs and on the increases in phosphorylation of myosin phosphatase target
      subunit 1 and myosin light chain (MLC) in aortic rings in response to
      hyperosmolar sucrose. Hyperosmolar sucrose-induced force was significantly
      attenuated by cytochalasin B in the presence or absence of DMA. Exposure to
      hyperosmolar sucrose increased the ratio of F- to G-actin; the ratio was further
      elevated by DMA. These results suggest that the potentiation of hyperosmotic
      shrinkage by NHE inhibition promotes actin polymerization in VSMCs and augments
      force production independent of changes in [Ca(2+)]i and MLC phosphorylation. 

PMID- 23872625
TI  - N-cholesteryl amino acid conjugates and their antimicrobial activities.
AB  - A series of N-cholesteryl amino acid conjugates have been synthesized using a
      reductive amination protocol in good yield and purity. All the synthesized
      conjugates were evaluated for their in vitro antimicrobial activities against
      Gram positive and Gram negative bacteria. Among the conjugates tested, N
      cholesteryl GABA 12 showed the highest potency toward the methicillin-resistant
      Staphylococcus aureus with the lowest MIC value of 2 MUg/mL. Hemolytic activities
      of the compounds 3, 4, 11, and 12 were determined. All compounds tested had no
      significant hemolytic activity up to >50 MUg/mL.

PMID- 23872627
TI  - A comparison of the robotic-assisted versus retropubic radical prostatectomy.
AB  - After Walsh's detailed anatomic description of pelvic anatomy in 1979, the
      retropubic radical prostatectomy (RRP) was the predominant surgical treatment for
      prostate cancer for more than twenty-five years. Over the past decade, however,
      the robotic-assisted radical prostatectomy (RARP) has grown increasingly popular
      and now is the most used surgical modality. Willingness to adopt this approach
      has been confounded by the novelty of technology and widespread marketing
      campaigns. In this article, we performed a literature search comparing radical
      retropubic prostatectomy to robotic-assisted radical prostetectomy with regard to
      perioperative, oncologic, and quality-of-life outcomes. We performed a PubMed
      literature search for a review of articles published between 2000 and 2013.
      Relevant articles were highlighted using the following keywords: robot or robotic
      prostatectomy, open or retropubic prostatectomy. Perioperative outcomes including
      decreased blood loss, fewer blood transfusions, and decreased length of hospital
      stay tend to favor RARP, while perioperative mortality is near negligible in
      both. Short-term positive surgical margins, prostate-specific antigen recurrence
      free survival, and need for salvage therapy following RARP are similar to RRP,
      though data at greater than ten years is limited. Preservation of urinary and
      sexual function and quality of life favored RARP, though this is dependent on
      surgeon technique. Finally, cost, though evolving, favors RRP. In our current
      state, most prostatectomies will continue to be perfromed robotically. Though
      there is evidence the robotic-assisted radical prostatectomy offers shorter
      lengths of stay, decreased intraoperative blood loss, faster return of sexual
      function and continence, there is a paucity on long-term oncologic outcomes.
      Rigorous, prospective randomized-controlled trials need to be performed to
      determine the long-term success of the robotic-assisted radical prostatectomy and
      whether it is cost-effective when its potential advantages are taken into
      consideration. 

PMID- 23872626
TI  - Organic vapor sorption method of isostructural solvates and polymorph of
      tenofovir disoproxil fumarate.
AB  - Tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir that belongs to a
      class of antiretroviral drugs, a nucleotide reverse transcriptase inhibitor. An
      acetonitrile solvate of TDF I, another new solvated form of TDF, was prepared and
      solid state characterization of its form was conducted using powder X-ray
      diffraction, FT-IR spectroscopy, and organic vapor sorption isotherm. During the
      characterization work, it was discovered that (1) TDF I can form solvates and
      polymorph with a wide variety of organic solvents as well as water and (2) to
      different extents, these solvates undergoes anisotropic lattice
      contraction/expansion during desolvation/solvation process suggesting the
      formation of isostructural solvates of TDF. Solvents used in this study include
      ethanol, isopropyl alcohol, acetonitrile, cyclohexane, toluene, and water. Four
      new solvates using ethanol, isopropyl alcohol, acetonitrile, and toluene vapor
      and one polymorph using water vapor were discovered. Their solid state
      characterizations were conducted using powder X-ray diffraction, differential
      scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared
      spectroscopy. A variety of isostructural solvates and a polymorph of TDF was
      produced by an organic vapor sorption method, showing varying physicochemical
      properties. This study demonstrates an alternative crystallization method to
      obtain isostructural solvates. 

PMID- 23872628
TI  - Metastatic castration-resistant prostate cancer: integrating new learnings to
      optimise treatment outcomes.
AB  - The approval or clinical evaluation of several new agents - cabazitaxel,
      abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has changed the
      management of patients with metastatic castration-resistant prostate cancer
      (mCRPC) prior to or after docetaxel-based chemotherapy significantly. All of
      these agents have resulted in a significant survival benefit as compared to their
      control group. However, treatment responses might differ depending on the
      associated comorbidities and the extent and the biological aggressiveness of the
      disease. Furthermore, treatment associated side effects differ between the
      various drugs. As new drugs become approved, new treatment strategies and markers
      to best select which patients will best respond to which drug are needed. It is
      the aim of the current article to: (1) summarize the data of established
      treatment options in mCRPC; (2) highlight new developments of medical treatment;
      (3) provide clinically useful algorithms for the daily routine and to (4) point
      out future developments of medical treatment. 

PMID- 23872629
TI  - Safety and efficacy of photoselective vaporization of prostate in patients
      receiving anticoagulants.
AB  - AIM: Objective of the present study was to evaluate the safety and efficacy of
      photoselective vaporization of the prostate (PVP) using a 80W potassium titanyl
      phosphate (KTP) laser, in benign prostatic enlargement (BPE) patients who were on
      ongoing anticoagulant therapy during the perioperative period. METHODS:
      Prospectively collected laser prostatectomy patient database of our hospital for
      the period between July 2009-Jan 2012 was retrospectively reviewed. Data on
      perioperative safety, functional outcome and complications up to follow-up at 6
      months of 45 eligible patients who underwent PVP-KTP and were on perioperative
      anticoagulant therapy (study group) was compared with 47 eligible patients who
      underwent PVP-KTP and were not on perioperative anticoagulant therapy (control
      group). P<0.05 was considered statistically significant. RESULTS: The baseline
      characteristics of the two groups were similar except for ASA score which was
      significantly higher in the study group.(2.64+/-0.60 vs. 1.53+/-0.50). Though the
      need (15.55% vs. 4.25% patients) and duration of postoperative irrigation
      (243.33+/-49.66 vs. 52.5+/-10.60 min) was significantly higher in the study
      group, the postoperative hemoglobin drop 24 hours postoperatively did not differ
      significantly between the two groups (8.54% vs. 6.48%). No patient required a
      blood transfusion. The overall complication rate was similar in the two groups.
      In both groups, significant improvement was recorded in the IPSS, QOL, Q max,
      PVRU and prostate volume data upto 6 months follow up with no significant
      differences noted. CONCLUSION: KTP-PVP can be performed safely and effectively in
      BPE patients on ongoing anticoagulation, without increasing the risk of
      perioperative bleeding or the need for blood transfusion.

PMID- 23872630
TI  - Continence recovery time after radical prostatectomy: implication of prostatic
      apical tumor.
AB  - AIM: Despite the role of prostatic apex on post-radical prostatectomy
      incontinence (PPI) has been encountered, the impact of prostatic apex tumor on
      urinary recovery has been poorly adressed. We aimed to evaluate the effect of
      prostatic apex tumor on PPI. METHODS: Between January 2008 and December 2011, a
      total 36 consecutive patients who underwent open retropubic radical prostatectomy
      (RRP) for prostate adenocancer (PCa) were analyzed. The patients were divided
      into two groups according to the presence of prostatic apical tumor. Urinary
      incontinence was assessed at regular intervals following RP using validated
      Incontinence Questionnaire-Short Form and 24-hour pad use based on patients'
      reports. Urinary continence was defined as wearing no pads. All patients'
      functional and oncological data were recorded. RESULTS: Overall urinary
      continence rate at one year was 90%. There was a statistical difference between
      two groups in terms of urinary recovery (P=0.024). The 1 week, 1 month, 3 month,
      6 months and 1 year postoperative continence rates were 28%, 50%, 85%, 92.9% and
      92.9%, respectively, in patients with apex infiltration (-) group, compared with
      0%, 22.7%, 45.5%, 72.7% and 86.4%, respectively, in patients with infiltration
      (+) group. CONCLUSION: The results provided that infiltration of the prostatic
      apex could significantly affect urinary continence recovery time after RP and
      advanced pathologic stage could be a risk for PPI.

PMID- 23872631
TI  - [Sildenafil assumption and acute effects on the uroflowmetric parameters].
AB  - AIM: In the recent literature, great attention has been given to the evaluation
      of the real effectiveness of the phosphodiesterase type 5 inhibitors (PDE-5i),
      usually prescribed for the erectile dysfunction (ED), in the treatment of the
      lower urinary tracts symptoms (LUTS). The aim of this study was the evaluation of
      the acute effects of sildenafil on the uroflowmetric parameters. METHODS: Within
      September 2011 and February 2012, twenty-seven patients, affected by ED with a
      IIEF-5 score <=21 and a contextual IPSS within 8 e 19, have been selected and
      enrolled in this study. Two uroflowmetric measurements with suprapubic ultrasound
      valuation of the post voiding residual (PVR) were performed on each patient, 2
      hours before and after the administration of sildenafil (50 mg). RESULTS: The
      average age of the patients came out within di 47.3+/-9.4 years. On the baseline,
      the average of the Qmax registered has been 15.6+/-3.3 mL/s, the average Qave has
      been 8.2+/-3.2 mL/s and the average resulted 32.5+/-11.4 mL. After the mono
      administration of sildenafil 50 mg, the average Qmax value, the Qave one and the
      RPM one turned out into 17.7+/-5.1 mL/s, 10.1+/-3.5 mL/s and 22.6+/-9.6 mL. The
      differences within the standard values, were considered statistically relevant
      (P<0.05). CONCLUSIONS: Actually, the study shows that, in the acute phase, the
      administration of sildenafil 50 mg leads to effects on the uroflowmetric
      standards on men affected by LUTS and DE.

PMID- 23872632
TI  - [Specific antigen prostatic changes during treatment with finasteride or
      dutasteride for benign prostatic hyperplasia].
AB  - AIM: The aim of this paper was to compare and analyze the therapeutic effects and
      PSA variation levels with treatment with finasteride-tamsulosin and dutasteride
      tamsulosin for benign prostatic hyperplasia for 2 years and the risk to
      developing prostate cancer for patients with PSA<4 ng/mL. METHODS: We
      retrospectively investigated 288 patients who suffered from BPH and PSA>4 ng/mL
      between January 2003 and July 2010. For treatment groups, we divided the patients
      into two groups: one was treated with tamsulosin and finasteride and the other
      with tamsulosin and dutasteride. At the beginning of treatment, the patients
      underwent transrectal ultrasonography and prostate mapping, measurement of urine
      flow rate, PSA, and International Prostate Symptom Score (IPSS). A total of 288
      patients were able to be. RESULTS: Both finasteride and dutasteride rduced PSA
      and prostate volume significantly. The comparison between the 2 groups showed a
      significant difference at 3 months for IPSS; uroflussimetry and prostate volume
      in the dutasteride group, but at 6 months did not differ significantly between
      the groups. Patients with a PSA reduction more than half presented a good
      response and didn't request surgical theraphy. CONCLUSION: 5 alpha Reductase
      inhibitors for BPH treatment reduced PSA and prostate volume significantly after
      6 months of theraphy and after 3 months only for dutasteride. PSA reduction is
      directly correlated with response to theraphy. Didn't were evidenced
      statistically differences on prostate cancer presence during theraphy.

PMID- 23872633
TI  - Statins in patients with chronic kidney disease: new evidence.
AB  - Dyslipidemia represents a common metabolic alteration in chronic kidney disease
      (CKD). Alterations can be different depending on the stage of the disease and the
      extent of proteinuria. Despite the high cardiovascular risk in patients with
      renal impairment, only a small percentage of patients receive adequate
      cholesterol-lowering therapy. The use of statins, inhibitors of the endogenous
      synthesis of cholesterol in patients with CKD, represents an efficient
      therapeutic instrument for reducing cardiovascular risk, at least in the early
      stage of the disease. Such evidence is currently lacking in dialysis, that is a
      setting where cardiovascular mortality is not consistently due to classical
      atherosclerosis. In addition to their efficacy, statins are proved as safe drugs
      with a high tolerability profile in CKD. In the case of intolerant patients, a
      new therapeutic perspective is represented by ezetimibe, inhibitor of intestinal
      absorption of cholesterol, whose effectiveness and tolerability allow its use
      throughout all stages of the renal disease. 

PMID- 23872634
TI  - Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a
      rare disease with high risk of sudden cardiac death.
AB  - Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A
      mutations in around 20% of cases. Through a genome-wide association study of 312
      individuals with Brugada syndrome and 1,115 controls, we detected 2 significant
      association signals at the SCN10A locus (rs10428132) and near the HEY2 gene
      (rs9388451). Independent replication confirmed both signals (meta-analyses:
      rs10428132, P = 1.0 * 10(-68); rs9388451, P = 5.1 * 10(-17)) and identified one
      additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 * 10(-14)). The
      cumulative effect of the three loci on disease susceptibility was unexpectedly
      large (Ptrend = 6.1 * 10(-81)). The association signals at SCN5A-SCN10A
      demonstrate that genetic polymorphisms modulating cardiac conduction can also
      influence susceptibility to cardiac arrhythmia. The implication of association
      with HEY2, supported by new evidence that Hey2 regulates cardiac electrical
      activity, shows that Brugada syndrome may originate from altered transcriptional
      programming during cardiac development. Altogether, our findings indicate that
      common genetic variation can have a strong impact on the predisposition to rare
      diseases. 

PMID- 23872635
TI  - Independent specialization of the human and mouse X chromosomes for the male germ
      line.
AB  - We compared the human and mouse X chromosomes to systematically test Ohno's law,
      which states that the gene content of X chromosomes is conserved across placental
      mammals. First, we improved the accuracy of the human X-chromosome reference
      sequence through single-haplotype sequencing of ampliconic regions. The new
      sequence closed gaps in the reference sequence, corrected previously misassembled
      regions and identified new palindromic amplicons. Our subsequent analysis led us
      to conclude that the evolution of human and mouse X chromosomes was bimodal. In
      accord with Ohno's law, 94-95% of X-linked single-copy genes are shared by humans
      and mice; most are expressed in both sexes. Notably, most X-ampliconic genes are
      exceptions to Ohno's law: only 31% of human and 22% of mouse X-ampliconic genes
      had orthologs in the other species. X-ampliconic genes are expressed
      predominantly in testicular germ cells, and many were independently acquired
      since divergence from the common ancestor of humans and mice, specializing
      portions of their X chromosomes for sperm production. 

PMID- 23872637
TI  - Predicting risk of 2-year incident dementia using the CAMCOG total and subscale
      scores.
AB  - BACKGROUND: being able to identify individuals at high risk of dementia is
      important for diagnostics and intervention. Currently, there is no standard
      approach to assessing cognitive function in older aged individuals to best
      predict incident dementia. OBJECTIVE: to identify cognitive changes associated
      with an increased risk of 2-year incident dementia using the Cambridge Cognitive
      Examination (CAMCOG). DESIGN: longitudinal population representative sample aged
      65+ years. METHODS: individuals were from the Medical Research Council Cognitive
      Function and Ageing Study. Classification and Regression Tree analysis was used
      to detect the optimal cut-off value for the CAMCOG total, subscales and composite
      memory and non-memory scores, for predicting dementia. Sensitivity and
      specificity of each cut-off score were assessed. RESULTS: from the 2,053
      individuals without dementia at the first assessment, 137 developed dementia at
      the 2-year follow-up. The results indicate similar discriminative accuracy for
      incident dementia based on the CAMCOG total, memory subscale and composite
      scores. However, sensitivity and specificity of cut-off values were generally
      moderate. Scores on the non-memory subscales generally had high sensitivity but
      low specificity. Compared with the CAMCOG total score they had significantly
      lower discriminative accuracy. CONCLUSION: in a population setting, cut-off
      scores from the CAMCOG memory subscales predicted dementia with reasonable
      accuracy. Scores on the non-memory scales have lower accuracy and are not
      recommend for predicting high-risk cases unless all non-memory subdomain scores
      are combined. The added value of cognition when assessed using the CAMCOG to
      other risk factors (e.g. health and genetics) should be tested within a risk
      prediction framework.

PMID- 23872638
TI  - Epigenetic regulation in vascular cells.
AB  - PURPOSE OF REVIEW: This review summarizes recent findings in the epigenetics of
      vascular cells and discusses the new challenges for therapeutic strategies of
      cardiovascular diseases. RECENT FINDINGS: There is emerging optimism that
      epigenetic mechanisms can provide the missing link to connect (epi)genomes with
      the cause of complex diseases. Environmental factors like intrauterine conditions
      during fetal development appear to preprogram humans for complex diseases. The
      purpose of this review is to summarize the newest results about the inheritable
      epigenetic features of cardiovascular diseases. Also, the recently discovered
      role of small RNAs in epigenetic gene regulation is discussed. SUMMARY:
      Epigenetic mechanisms of gene regulation will likely become major determinants in
      the pathogenesis of complex diseases and may offer new opportunities for the
      treatment of these diseases.

PMID- 23872636
TI  - DYX1C1 is required for axonemal dynein assembly and ciliary motility.
AB  - DYX1C1 has been associated with dyslexia and neuronal migration in the developing
      neocortex. Unexpectedly, we found that deleting exons 2-4 of Dyx1c1 in mice
      caused a phenotype resembling primary ciliary dyskinesia (PCD), a disorder
      characterized by chronic airway disease, laterality defects and male infertility.
      This phenotype was confirmed independently in mice with a Dyx1c1 c.T2A start
      codon mutation recovered from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen.
      Morpholinos targeting dyx1c1 in zebrafish also caused laterality and ciliary
      motility defects. In humans, we identified recessive loss-of-function DYX1C1
      mutations in 12 individuals with PCD. Ultrastructural and immunofluorescence
      analyses of DYX1C1-mutant motile cilia in mice and humans showed disruptions of
      outer and inner dynein arms (ODAs and IDAs, respectively). DYX1C1 localizes to
      the cytoplasm of respiratory epithelial cells, its interactome is enriched for
      molecular chaperones, and it interacts with the cytoplasmic ODA and IDA assembly
      factor DNAAF2 (KTU). Thus, we propose that DYX1C1 is a newly identified dynein
      axonemal assembly factor (DNAAF4). 

PMID- 23872640
TI  - Ring-opening polymerization of cyclic esters by phenoxy-thioether complexes
      derived from biocompatible metals.
AB  - A series of novel Mg(II) and Zn(II) complexes of the form LMX or L2M, supported
      by phenoxy-thioether ligands bearing different substituents at the ortho position
      of the thiophenol rings [L(-) = 4,6-tBu2-OC6H2-2-CH2S(2-R-C6H4)(-)] [M = Zn, R =
      H, X = N(SiMe3)2 (1) and X = Et (2); M = Mg, X = n-Bu, R = H (3), R = CH3 (4), R
      = Br (5); M = Mg, R = H (6)], were synthesized and characterized. Reaction of the
      proper zinc precursor (Zn[N(SiHMe2)2]2 or ZnEt2) with one equivalent of the
      phenoxy-thioether proligand produced the corresponding amido (1) and ethyl (2)
      zinc complexes in high yields. The monoalkylmagnesium complexes (3-5) were all
      obtained by butane elimination reaction of the dialkylmagnesium reagent, Mg(n
      Bu)2, with one equivalent of the proligand in good yields. The homoleptic complex
      6 was obtained by reaction of 0.5 equivalent of Mg(n-Bu)2 and the proper
      proligand. Variable temperature (1)H NMR studies performed on 2 and 3
      demonstrated that the named complexes are involved in fluxional processes
      concerning a fast conformational change of the six-membered metallacycle. DOSY
      (Diffusion Ordered SpectroscopY) (1)H experiments and ligand scrambling strongly
      suggested that complexes 1-6 exist as dimeric species in solution. All complexes
      were active as catalysts in the ring-opening polymerization of cyclic esters. In
      particular, magnesium complexes showed superior epsilon-caprolactone and lactide
      ROP behavior in terms of activity, control of molecular weights and molecular
      weight distributions.

PMID- 23872642
TI  - Time-resolved dynamics of granular matter by random laser emission.
AB  - Because of the huge commercial importance of granular systems, the second-most
      used material in industry after water, intersecting the industry in multiple
      trades, like pharmacy and agriculture, fundamental research on grain-like
      materials has received an increasing amount of attention in the last decades. In
      photonics, the applications of granular materials have been only marginally
      investigated. We report the first phase-diagram of a granular as obtained by
      laser emission. The dynamics of vertically-oscillated granular in a liquid
      solution in a three-dimensional container is investigated by employing its random
      laser emission. The granular motion is function of the frequency and amplitude of
      the mechanical solicitation, we show how the laser emission allows to distinguish
      two phases in the granular and analyze its spectral distribution. This
      constitutes a fundamental step in the field of granulars and gives a clear
      evidence of the possible control on light-matter interaction achievable in grain
      like system. 

PMID- 23872641
TI  - [Colour-coded duplex-sonography versus scintigraphy. Can scintigraphy be replaced
      by sonography for diagnosis of functional thyroid autonomy?].
AB  - Since the development of colour coded duplex-sonography (ccds), several attempts
      have been made to implement this technique for diagnosis of focal lesions in the
      thyroid. There are controversial discussions on whether ccds might replace
      thyroid scintigraphy in diagnosis of hyperfunctional thyroid nodules. Aim of this
      study was the comparison of ccds and thyroid scintigraphy in diagnosis of
      functional thyroid autonomy. PATIENTS, MATERIAL AND METHODS: 192 patients with
      thyroid nodules > 10mm detected by conventional sonography underwent thyroid
      scintigraphy. Additionally, these patients were subjected to ccds of the thyroid.
      In total, 286 thyroid nodules were examined by scintigraphy, ccds and blood
      tests. RESULTS: Thyroid scintigraphy showed 67% of thyroid nodules as
      hyperfunctional, 19% indifferent and 14% as hypofunctional. Mean 99mTc uptake of
      hyperfunctional nodules was 2.19%, of indifferent nodules 1.12% and of
      hypofunctional nodules 1.06% respectively. The ccds allowed perinodular
      measurement of flow speed (hyperfunctional: 0.23 +/- 0.1 m/s; hypofunctional:
      0.22 +/- 0.1; indifferent: 0.21 +/- 0.09), resistance index (hyperfunctional:
      1.21 +/- 1.16; hypofunctional: 0.62 +/- 0.48; indifferent: 0.93 +/- 1.02) and
      pulsatility index (hyperfunctional: 0.97 +/- 0.45; hypofunctional: 0.84 +/- 0.4;
      indifferent: 1.04 +/- 0.6) in all nodules as well as intranodular measurement in
      some of the nodules (24% in hyperfunctional, 2% in indifferent and 15% in
      hypofunctional nodules). Statistic analysis of the obtained ccds data did not
      show any practically relevant correlations (p>0.05) with 99mTc uptake, basal TSH,
      fT3 or fT4. CONCLUSION: Thyroid scintigraphy cannot be replaced by ccds for
      diagnosis of functional thyroid autonomy. Reliable diagnostics still require a
      combination of thyroid scintigraphy, sonography and blood tests.

PMID- 23872643
TI  - The Journal Citation Reports Impact Factor: annual results 2012.

PMID- 23872639
TI  - Age-related changes in the innervation of the prostate gland: implications for
      prostate cancer initiation and progression.
AB  - The adult prostate gland grows and develops under hormonal control while its
      physiological functions are controlled by the autonomic nervous system. The
      prostate gland receives sympathetic input via the hypogastric nerve and
      parasympathetic input via the pelvic nerve. In addition, the hypogastric and
      pelvic nerves also provide sensory inputs to the gland. This review provides a
      summary of the innervation of the adult prostate gland and describes the changes
      which occur with age and disease. Growth and development of the prostate gland is
      age dependent as is the occurrence of both benign prostate disease and prostate
      cancer. In parallel, the activity and influence of both the sympathetic and
      parasympathetic nervous system changes with age. The influence of the sympathetic
      nervous system on benign prostatic hyperplasia is well documented and this review
      considers the possibility of a link between changes in autonomic innervation and
      prostate cancer progression. 

PMID- 23872644
TI  - Personalised antiplatelet therapy: are we ready for prime time? Data from China.

PMID- 23872645
TI  - Clinical assessment, platelet reactivity measurement or genetic testing after
      acute coronary syndrome? What benefits the patient?

PMID- 23872646
TI  - Polymer coatings on drug-eluting stents: Samson's hair and Achilles' heel?

PMID- 23872647
TI  - Six-month IVUS and two-year clinical outcomes in the EVOLVE FHU trial: a
      randomised evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting
      stent.
AB  - AIMS: The EVOLVE FHU trial demonstrated non-inferiority of six-month late loss
      with two dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus
      eluting stent (EES) compared with the durable polymer PROMUS Element (PE) EES.
      The current analysis describes the six-month IVUS and clinical results through
      two years from the EVOLVE FHU trial. METHODS AND RESULTS: EVOLVE recruited 291
      patients from 29 centres. At six months, IVUS-assessed in-stent net volume
      obstruction was 3.40 +/- 5.06% for PROMUS Element (PE) vs. 2.68 +/- 4.60% for
      SYNERGY (p=0.34) and 3.09 +/- 4.29% for SYNERGY 1/2 dose (p=0.68 vs. PE). There
      were no significant differences between groups for any other measured IVUS
      parameter including resolved, persistent, and late-acquired incomplete stent
      apposition (ISA). At two years, target lesion failure (TLF) was 6.1% for PE vs.
      5.5% for SYNERGY (p=0.87) and 5.2% for SYNERGY 1/2 dose (p=0.81). There were no
      significant differences between groups for cardiac death, repeat
      revascularisation, MI or stent thrombosis through two years. CONCLUSIONS: At six
      months, everolimus delivered from an ultrathin bioabsorbable abluminal polymer
      resulted in equivalent net volume obstruction and ISA compared with a permanent
      polymer EES. There were no significant differences between PE and either SYNERGY
      stent for any major cardiac endpoint through two years. Clinical trials number:
      NCT01135225.

PMID- 23872648
TI  - The impact of gene polymorphism and high on-treatment platelet reactivity on
      clinical follow-up: outcomes in patients with acute coronary syndrome after drug
      eluting stent implantation.
AB  - AIMS: The current study sought to evaluate the clinical impact of newly reported
      genetic variations and their association with clopidogrel high on-treatment
      platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients after drug
      eluting stent (DES) implantation. METHODS AND RESULTS: The study enrolled 1,016
      consecutive patients with ACS undergoing DES implantation. A total of 19 tag
      single nucleotide polymorphisms (SNPs) were selected from CYP3A4/5, CYP2C19,
      P2Y12 and ABCB1 genes. ADP-induced light transmittance aggregometry (LTA) was
      performed to test the post-procedure maximum platelet agglutination (MPA). The
      primary endpoint was a composite of cardiovascular death, non-fatal myocardial
      infarction (MI), stent thrombosis, and ischaemic stroke at one-year follow-up
      after DES placement. The secondary endpoint was the incidence of bleeding events.
      The post-procedure MPA was calculated and the cut-off point was determined for
      the HTPR. Using multivariate logistic regression analysis, the carriage of two
      CYP2C19 LOF alleles was an independent predictor of the post-procedure HTPR (OR:
      2.8, 95% CI: 1.70-7.23, p<0.001). Through multivariate Cox regression analysis,
      the carriage of two CYP2C19 LOF alleles and the post-procedure HTPR were
      independent predictors of the primary endpoint (HR: 2.3, 95% CI: 1.40-4.97,
      p<0.001; HR: 2.9, 95% CI: 1.52-5.57, p<0.001, respectively). However, post
      procedure MPA did not predict a bleeding event (HR: 0.9, 95% CI: 0.44-1.59,
      p=0.532). CONCLUSIONS: In patients with ACS, the CYP2C19 LOF allele was
      associated with post-procedure HTPR and a subsequently increased risk of adverse
      clinical events at one-year follow-up following DES implantation and clopidogrel
      administration.

PMID- 23872649
TI  - Full conversion from transfemoral to transradial approach for percutaneous
      coronary interventions results in a similar success rate and a rapid reduction of
      in-hospital cardiac and vascular major events.
AB  - AIMS: The transradial approach (TRA) for percutaneous coronary intervention (PCI)
      recently emerged as a safer vascular access with a similar rate of MACE but a
      lower success rate requiring crossover to another approach when compared to the
      transfemoral approach (TFA). METHODS AND RESULTS: In our hospital the
      introduction of the TRA in November 2003 resulted in a progressive decline of TFA
      use. Over the five years of conversion to TRA, from 2002 (100% TFA) to 2007 (98%
      TRA), major adverse cardiac events (MACE) and all in-hospital vascular and
      bleeding events, related or not to vascular access, were prospectively collected
      to assess performances of each approach in the specific setting of PCI
      (percutaneous coronary interventions). Data of 1,928 TFA and 1,672 TRA for a
      total of 3,600 consecutive PCI procedures are reported. PCI success rate was
      unchanged by TRA (96.1% versus 95.3% for TFA, NS). TRA was associated with a
      reduction in the rate of post-PCI myocardial infarction (2.3% versus 3.6% for
      TFA, p=0.023) and with a significant reduction of MACE (3.8% versus 5.2% for TFA,
      p=0.041). TRA use was also associated with a marked reduction of blood
      transfusion and surgery for post-PCI bleeding (0.2% versus 1.5% for TFA,
      p<0.001), despite more frequent prescription of downstream glycoprotein IIb/IIIa
      inhibitors (23.7% versus 7.4% for TFA, p<0.001). Thus, TRA resulted in a rapid
      and significant reduction of all major in-hospital adverse events, cardiac as
      well as non-cardiac, pooled in a "Net Adverse Clinical Event (NACE) index" of non
      desirable events: death, myocardial infarction, stroke, urgent CABG surgery,
      surgery for bleeding and vascular events and blood transfusion. Such events
      occurred in 4.1% of TRA (n=69) as compared to 7% of TFA (n=134) (p<0.001),
      accounting for a 41% relative reduction of this NACE index by TRA. By
      multivariate analysis, TRA was related to a better in-hospital outcome (OR 0.64,
      95% confidence interval [CI] 0.47-0.87; p=0.005). CONCLUSIONS: TRA for PCI
      provides the same success rate as TFA but significantly reduces post hoc related
      complications.

PMID- 23872650
TI  - Gender differences in patients undergoing TAVI: a multicentre study.
AB  - AIMS: In patients undergoing surgical valve replacement for severe aortic
      stenosis, female gender was associated with worse outcomes, not persisting after
      multivariable adjustment for baseline clinical differences, while contrasting
      data are reported about TAVI. METHODS AND RESULTS: From January 2007 to December
      2011 all patients with severe symptomatic aortic stenosis undergoing TAVI at our
      institutions were included in the present study, and were divided into two
      cohorts according to their gender. All endpoints were adjudicated according to
      VARC definition. Three hundred and seventy-seven patients were included: 161 male
      and 216 female. Male patients reported higher rates of previous coronary
      revascularisation, while both ejection fraction and mean aortic gradient were
      higher in female patients. At 30 days, rates of cardiovascular death were similar
      (6.0% vs. 8.1%; p=0.793), while overall bleedings (44% vs. 25%; p=0.024) and life
      threatening bleedings (21.1% vs. 12.7%, p=0.016) were higher in female patients,
      also after multivariate analysis (OR 3.44; 1.23-9.22, and OR 2.1; 1.1-4.0, CI:
      95%, respectively). Major vascular complications showed a tendency to be higher
      in female patients (12.9% vs. 9.8%, p=0.449). At a mean follow-up of 490 +/- 250
      days, no significant difference was reported between men and women for all
      endpoints, and after multivariate adjustment only life-threatening bleeding was
      reported as a predictor of death (OR 8.2:3.8-17, CI: 95%). CONCLUSIONS: TAVI can
      be an effective and safe strategy in high surgical risk patients, regardless of
      the gender; life-threatening bleedings were reported more frequently in female
      patients, being the only independent predictor of death.

PMID- 23872651
TI  - Health-related quality of life in the elderly three years after percutaneous
      coronary intervention.
AB  - AIMS: Long-term health-related quality of life (HRQOL) in the elderly after
      percutaneous coronary intervention (PCI) is unknown. We 1) compared HRQOL of
      elderly (>=70 years) with younger patients (<70 years) at 6, 12, 36 months post
      PCI, and 2) examined whether predictors of impaired HRQOL 36 months post-PCI
      differed between older and younger patients. METHODS AND RESULTS: A prospective
      cohort of 651 PCI patients (26.3% >=70 years) completed the SF-36 at 6, 12 and 36
      months post-PCI. Older patients experienced a poorer physical HRQOL at all time
      points and worse mental HRQOL with respect to vitality and role emotional
      functioning (all p-values<0.05). By 36 months, the HRQOL for the older patients
      worsened in five of the eight subdomains (all p-values<0.05). Younger patients
      did not experience enduring changes in HRQOL, with the exception of role physical
      functioning. Predictors of impaired HRQOL were generally different for the
      elderly (diabetes, previous PCI) compared to younger cohorts (smoking, previous
      bypass surgery, ACE inhibitors), although poor six-month HRQOL, anxiety and
      depression were common predictors for both groups. CONCLUSIONS: Elderly PCI
      patients experience a deteriorating and poorer HRQOL than younger patients across
      three years. Contrary to younger patients, three-year HRQOL of elderly patients
      is irrespective of adverse events during outcomes.

PMID- 23872652
TI  - Residual shunt after percutaneous closure of patent foramen ovale with AMPLATZER
      occluder devices - influence of anatomic features: a transcranial Doppler and
      intracardiac echocardiography study.
AB  - AIMS: To evaluate the relationship between the anatomic features of the fossa
      ovalis (FO) and residual right-to-left shunt (RLS) after percutaneous patent
      foramen ovale (PFO) closure with AMPLATZER PFO occluder devices. METHODS AND
      RESULTS: FO anatomic features were assessed by intracardiac echocardiography in
      127 patients with large RLS at contrast-enhanced transcranial colour Doppler
      (TCCD) undergoing percutaneous PFO closure with an AMPLATZER device. Residual RLS
      was evaluated by TCCD three and 12 months after the procedure. PFO closure was
      successful in all but two patients. At TCCD, a significant residual RLS (grade
      >=2) was observed in 27 (21.6%) and 17 (13.6%) patients at three and 12 months,
      respectively. Larger baseline RLS, presence of atrial septal aneurysm, greater
      longitudinal and transverse FO dimensions, and use of larger devices were
      associated with significant residual RLS. At multivariate analysis, the presence
      of atrial septal aneurysm (OR 7.6; 95% CI: 1.38-42.35; p=0.02) and longitudinal
      FO dimension >20.8 mm (OR 8.5; 95% CI: 1.55-46.95; p=0.014) were identified as
      independent predictors of significant residual RLS at 12 months. CONCLUSIONS: Our
      study suggests that a large FO and the presence of atrial septal aneurysm are
      independent predictors of persistent residual RLS after PFO closure with
      AMPLATZER devices.

PMID- 23872653
TI  - Detailed analysis of polymer response to delivery balloon expansion of drug
      eluting stents versus bare metal stents.
AB  - AIMS: We sought to describe the response of the polymer surface of drug-eluting
      stents (DES) to delivery balloon expansion, including quantitation of any
      resulting detached microparticles. METHODS AND RESULTS: We expanded the US Food
      and Drug Administration (FDA)-approved first- and second-generation DES in a
      vacuum filtration system and used optical and scanning electron microscopy to
      image the polymer surface, filters and delivery balloons. DES were expanded under
      a range of conditions, from in vitro conditions used for FDA regulatory
      submissions to human in vivo conditions. Dispersive Raman spectroscopy was used
      for definitive identification of microparticles. All polymer surfaces were
      topographically disturbed over an average of 4.6%-100% of the surface area
      imaged. Disturbances ranged from deformation (including peeling) to complete
      delamination. The dimensions of detached microparticles were 2-350 MUm. The
      extent and nature of surface disturbances and microparticles were primarily a
      function of polymer composition (p<0.001 for 8/10 disturbance types/locations)
      and were independent of expansion condition (p=0.100 to 0.989 for 9/10
      disturbance types/locations). CONCLUSIONS: Balloon expansion of first- and second
      generation DES disturbs the polymer surface and can cause detachment of
      microparticles; each is functionally related to the specific polymer but not to
      expansion condition. Disturbance "roughness" and detached microparticles may
      contribute to DES limitations.

PMID- 23872654
TI  - Effect of pressure-controlled intermittent coronary sinus occlusion (PICSO) on
      myocardial ischaemia and reperfusion in a closed-chest porcine model.
AB  - AIMS: To investigate a pressure-controlled intermittent coronary sinus occlusion
      (PICSO) system in an ischaemia/reperfusion model. METHODS AND RESULTS: We
      randomly assigned 18 pigs subjected to 60 minutes ischaemia by left anterior
      descending (LAD) coronary artery balloon occlusion to PICSO (n=12, groups A and
      B) or to controls (n=6, group C). PICSO started 10 minutes before (group A), or
      10 minutes after (group B) reperfusion and was maintained for 180 minutes. A
      continuous drop of distal LAD pressure was observed in group C. At 180 minutes of
      reperfusion, LAD diastolic pressure was significantly lower in group C compared
      to groups A and B (p=0.02). LAD mean pressure was significantly less than the
      systemic arterial mean pressure in group C (p=0.02), and the diastolic flow slope
      was flat, compared to groups A and B (p=0.03). IgG and IgM antibody deposition
      was significantly higher in ischaemic compared to non-ischaemic tissue in group C
      (p<0.05). Significantly more haemorrhagic lesions were seen in the ischaemic
      myocardium of group C, compared to groups A and B (p=0.002). The necrotic area
      differed non-significantly among groups. CONCLUSIONS: PICSO was safe and
      effective in improving coronary perfusion pressure and reducing antibody
      deposition consistent with reduced microvascular obstruction and
      ischaemia/reperfusion injury.

PMID- 23872655
TI  - How should I treat prosthetic tricuspid stenosis in an extreme surgical risk
      patient?
AB  - BACKGROUND: A 64-year-old female with rheumatic heart disease and multiple prior
      valve replacements presented with progressive oedema, ascites and dyspnoea on
      exertion. INVESTIGATION: Physical examination, transthoracic echocardiography,
      intracardiac echocardiography, transoesophageal echocardiography, right heart
      cathetherisation, computed tomography. DIAGNOSIS: She had a mitral homograft and
      Physio ring in the tricuspid position, and presented with severe bioprosthetic
      tricuspid valve stenosis (mean gradient 16 mmHg) and right-sided heart failure.
      TREATMENT: A transcatheter 26 mm Edwards SAPIEN valve was placed in the tricuspid
      position, resulting in near normalisation of tricuspid valve gradient. This
      represents the first report of a combined valve-in-ring (VIR) and valve in a
      homograft valve (VIV) SAPIEN implantation.

PMID- 23872656
TI  - Tools & techniques methodology and statistics: randomisation in clinical trials.

PMID- 23872657
TI  - Multivariate spatial models of excess crash frequency at area level: case of
      Costa Rica.
AB  - Recently, areal models of crash frequency have being used in the analysis of
      various area-wide factors affecting road crashes. On the other hand, disease
      mapping methods are commonly used in epidemiology to assess the relative risk of
      the population at different spatial units. A natural next step is to combine
      these two approaches to estimate the excess crash frequency at area level as a
      measure of absolute crash risk. Furthermore, multivariate spatial models of crash
      severity are explored in order to account for both frequency and severity of
      crashes and control for the spatial correlation frequently found in crash data.
      This paper aims to extent the concept of safety performance functions to be used
      in areal models of crash frequency. A multivariate spatial model is used for that
      purpose and compared to its univariate counterpart. Full Bayes hierarchical
      approach is used to estimate the models of crash frequency at canton level for
      Costa Rica. An intrinsic multivariate conditional autoregressive model is used
      for modeling spatial random effects. The results show that the multivariate
      spatial model performs better than its univariate counterpart in terms of the
      penalized goodness-of-fit measure Deviance Information Criteria. Additionally,
      the effects of the spatial smoothing due to the multivariate spatial random
      effects are evident in the estimation of excess equivalent property damage only
      crashes. 

PMID- 23872659
TI  - Integration of ligand and structure-based virtual screening for identification of
      leading anabolic steroids.
AB  - Parallel ligand- and structure-based virtual screenings of 269 steroids with
      anabolic activity evaluated in vivo were performed. The quantitative structure
      activity relationship (QSAR) model expressed by selected descriptors as the
      octanol-water partition coefficient, the molar volume and the quantum mechanical
      calculated charge values on atoms C1, C2, C5, C9, C10, C14 and C17 of the steroid
      skeleton, expresses structural features of anabolic steroids (AS) contributing to
      the transport and steroid-receptor interaction. On the other hand, computational
      simulations of a candidate ligand binding to a receptor study (a "docking"
      procedure) predict the association of these AS with the human androgen receptor
      (AR). Fourteen compounds were identified as lead; the most potent was the 7alpha
      methylestr-4-en-3, 17-dione. It was concluded that a good anabolic activity
      requires hydrogen bonding interactions between both Arg752 and Gln711 residues in
      the cycles A with O3 atom of the steroid and either Asn705 and Thr877 residues in
      the cycles D of steroid with O17 atom. 

PMID- 23872658
TI  - M(o)TOR of aging: MTOR as a universal molecular hypothalamus.
AB  - A recent ground-breaking publication described hypothalamus-driven programmatic
      aging. As a Russian proverb goes "everything new is well-forgotten old". In 1958,
      Dilman proposed that aging and its related diseases are programmed by the
      hypothalamus. This theory, supported by beautiful experiments, remained unnoticed
      just to be re-discovered recently. Yet, it does not explain all manifestations of
      aging. And would organism age without hypothalamus? Do sensing pathways such as
      MTOR (mechanistic Target of Rapamycin) and IKK-beta play a role of a "molecular
      hypothalamus" in every cell? Are hypothalamus-driven alterations simply a part of
      quasi-programmed aging manifested by hyperfunction and secondary signal
      resistance? Here are some answers. 

PMID- 23872660
TI  - Loss of starch granule initiation has a deleterious effect on the growth of
      arabidopsis plants due to an accumulation of ADP-glucose.
AB  - STARCH SYNTHASE4 (SS4) is required for proper starch granule initiation in
      Arabidopsis (Arabidopsis thaliana), although SS3 can partially replace its
      function. Unlike other starch-deficient mutants, ss4 and ss3/ss4 mutants grow
      poorly even under long-day conditions. They have less chlorophyll and carotenoids
      than the wild type and lower maximal rates of photosynthesis. There is evidence
      of photooxidative damage of the photosynthetic apparatus in the mutants from
      chlorophyll a fluorescence parameters and their high levels of malondialdehyde.
      Metabolite profiling revealed that ss3/ss4 accumulates over 170 times more ADP
      glucose (Glc) than wild-type plants. Restricting ADP-Glc synthesis, by
      introducing mutations in the plastidial phosphoglucomutase (pgm1) or the small
      subunit of ADP-Glc pyrophosphorylase (aps1), largely restored photosynthetic
      capacity and growth in pgm1/ss3/ss4 and aps1/ss3/ss4 triple mutants. It is
      proposed that the accumulation of ADP-Glc in the ss3/ss4 mutant sequesters a
      large part of the plastidial pools of adenine nucleotides, which limits
      photophosphorylation, leading to photooxidative stress, causing the chlorotic and
      stunted growth phenotypes of the plants. 

PMID- 23872661
TI  - Castrate-tolerant cells: what are the implications for the treatment of localized
      prostate cancer?
AB  - More effective treatment of prostate cancer relies on eliminating cells that
      survive androgen withdrawal therapy. The discovery that castrate-tolerant tumour
      cells pre-exist in localized prostate cancer, prior to androgen withdrawal or
      progression to castrate-resistant disease, supports the notion that neo-adjuvant
      therapies might be considered in the management of early stage prostate cancer.
      Advances in our ability to xenograft human prostate cancer provides a unique
      model system to study individual patient responses and test the preclinical
      efficacy of novel compounds for men with localized disease.

PMID- 23872662
TI  - Nerve growth factor signaling following unilateral pelvic ganglionectomy in the
      rat ventral prostate is age dependent.
AB  - Benign prostatic hyperplasia (BPH) is a serious health concern and is an
      underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected
      men, LUTS/BPH is believed to result from benign proliferation of the prostate
      resulting in bladder outlet obstruction. Postnatal growth of the prostate is
      controlled via growth factor and endocrine mechanisms. However, little attention
      had been given to the function of the autonomic nervous system in prostate growth
      and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a
      trophic role in autonomic sensory end organ interaction. In this study, we
      examine how the autonomic nervous system influences prostate growth as a function
      of age by quantifying NGF in the rat ventral prostate (VP) after pelvic
      ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days
      30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n=39).
      Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for
      NGF were performed on denervated, intact (contralateral side) and sham control VP
      7 days after surgery. Ngf RNA expression was significantly increased in the
      denervated and intact hyperplastic VP. Western blotting showed age-dependent
      increases in NGF protein at P60 in the contralateral intact VP. NGF was localized
      in the nerves, basal cells and columnar epithelium of the prostatic ducts.
      Denervation causes age-dependent increases in NGF in the VP, which is a potential
      mechanism by which the autonomic nervous system may regulate prostate growth and
      lead to BPH/LUTS.

PMID- 23872663
TI  - Interracial differences in prostate cancer progression among patients from the
      United States, China and Japan.
AB  - Although previous studies indicate interracial differences in prostate cancer
      epidemiology based on gene expression profiles among patients from the United
      States, China and Japan, evidence at the genetic and phenotypic levels that these
      differences exist and manifest along ethnic lines has been sparse. Recent
      studies, however, suggest that genetic differences, such as the lower incidence
      of Chinese prostate cancers harboring TMPRSS2-ERG translocations compared to
      patients from Western countries, should be carefully considered in the context of
      genotypic and phenotypic differences among interracial groups. New, more
      efficient technologies need to be developed to validate genetic, gene expression
      and/or phenotypic differences associated with prostate cancer tissue specimens
      obtained from interracial groups, to establish reliable clinical standards that
      take racial/ethnic data into account to improve the diagnosis, prognosis and
      treatment of patients with prostate cancer.

PMID- 23872664
TI  - Penile prosthesis implantation in Chinese patients with severe erectile
      dysfunction: 10-year experience.
AB  - We retrospectively evaluated the clinical outcome of penile prosthesis
      implantation (PPI) in Chinese patients with severe erectile dysfunction (SED).
      From July 2000 to December 2011, 224 patients (mean age: 35.9+/-11.8 years,
      range: 20-75 years) with SED underwent PPI by experienced surgeon according to
      standard PPI procedure at our centre. A malleable prosthesis (AMS 650) was
      implanted in 45 cases (20.1%), and a three-piece inflatable prosthesis (AMS 700
      CXM or AMS 700 CXR) was implanted in 179 cases (79.9%). Surgical outcomes,
      including postoperative complications, clinical efficacy and couple satisfaction,
      were evaluated over than 6 months postoperatively using medical record
      abstraction, IIEF-5, quality of life (QoL) scores, and the patient/partner sexual
      satisfaction score proposed by Bhojwani et al. Of the 224 patients eligible for
      the study, 201 subjects (89.7%) completed follow-up. All of patients could
      perform sexual intercourse post PPI with the mean postoperative IIEF-5 and QoL
      scores were 20.02+/-2.32 and 5.28+/-0.76, respectively, which were significantly
      improved compared with the preoperative scores (6.29+/-1.5 and 2.13+/-0.84,
      P<0.01). Of the 201 men, mechanical malfunction occurred in four cases (2.0%) and
      three cases were re-implanted new device, and two cases (1.0%) developed a mild
      curvature of the penis. Scrotal erosion with infection occurred in one case with
      diabetes mellitus (0.5%) and required complete removal of the implanted AMS 700
      CXM. Satisfactory sexual intercourse at least twice per month was reported by 178
      men (88.6%), and overall satisfaction with the PPI surgery was reported by 89.0%
      of men and 82.5% of partners. Patient satisfaction in the three-piece inflatable
      prosthesis group was higher than in the malleable prosthesis group (P<0.05).
      Satisfaction, however, between the types of prostheses, did not differ in the
      partner survey. PPI is a safe and effective treatment option for Chinese patients
      with SED and experienced surgeon perform PPI according to standard PPI procedure
      could reduce the postoperative complications of PPI and could improve patient
      satisfaction ratio and QoL. 

PMID- 23872665
TI  - A genetic polymorphism in lincRNA-uc003opf.1 is associated with susceptibility to
      esophageal squamous cell carcinoma in Chinese populations.
AB  - The development of esophageal squamous cell carcinoma (ESCC) is a multifactorial
      process, and associations between genetic variants and ESCC have been identified
      in genome-wide association studies. The aim of this study was to evaluate the
      effects of single nucleotide polymorphisms (SNPs) of long intergenic non-coding
      RNAs (lincRNAs) on ESCC susceptibility in Chinese populations. We scoured exons
      of lincRNAs located in ESCC susceptibility loci for all probable functional SNPs.
      These 52 SNPs were opted for and genotyped in 1493 ESCC patients and 1553 cancer
      free controls from eastern and southern Chinese populations, and their
      associations with the risk for ESCC were estimated using logistic regression.
      Functional relevance was further examined by biochemical assays. Significant
      differences were found between patients and controls in the genotype frequencies
      for the rs11752942A>G site in the lincRNA-uc003opf.1 exon. Compared with the
      rs11752942AA genotype, AG and GG genotypes had a significantly reduced risk of
      ESCC (adjusted odds ratio = 0.73; 95% confidence interval = 0.63-0.84).
      Biochemical analysis demonstrated that, when compared with the A allele, the
      rs11752942G allele could markedly attenuate the level of lincRNA-uc003opf.1 both
      in vivo and in vitro by binding micro-RNA-149*, thereby affecting cell
      proliferation and tumor growth. These findings indicated that functional
      polymorphism rs11752942A>G in lincRNA-uc003opf.1 exon might be a genetic modifier
      for the development of ESCC. 

PMID- 23872666
TI  - Identification and association study with lung cancer for novel insertion
      polymorphisms of human endogenous retrovirus.
AB  - Sequences of human endogenous retroviruses (HERVs) are members of the long
      terminal repeat (LTR) retrotransposon family. Although the expression of HERV has
      long been a topic of investigation, HERV-insertion polymorphisms are not well
      known, and a genetic association between HERV-insertion polymorphisms and cancer
      has never been reported. To identify novel HERV loci in the genome from cancer
      tissues, we carried out the inverse PCR method targeting a conserved LTR region
      of HML-2, which is the most recently acquired HERV group. Novel two insertions,
      HML-2_sLTR(1p13.2) and HML-2_sLTR(19q12), were identified as insertionally
      polymorphic solo LTRs. Furthermore, a significant prevalence of HML
      2_sLTR(1p13.2) homozygosity was detected in female never-smoking patients aged 60
      years and over who had lung adenocarcinoma [versus the other genotyping; odds
      ratio (OR): 1.97; 95% confidence interval (CI): 1.01-3.81]. In another cohort
      consisting of female never-smoking patients with lung adenocarcinoma, a
      prevalence of HML-2_sLTR(1p13.2) homozygosity tended to be high in patients aged
      60 years and over (versus the other genotyping; OR: 2.03; 95% CI: 0.96-4.29),
      whereas a low prevalence of HML-2_sLTR(1p13.2) homozygosity was detected in
      patients <60 years old (versus the other genotyping; OR: 0.31; 95% CI: 0.11
      0.94). Our results suggest that HML-2_sLTR(1p13.2) is involved with the
      susceptibility to lung adenocarcinoma in female never-smokers in an age-dependent
      manner and that other HERV polymorphisms related to human diseases might remain
      to be identified in the human genome. 

PMID- 23872667
TI  - Controlled synthesis of spinel ZnFe2O4 decorated ZnO heterostructures as
      peroxidase mimetics for enhanced colorimetric biosensing.
AB  - Controlled synthesis of spinel ZnFe2O4 nanoparticle-decorated ZnO nanofiber
      heterostructures was carried out with regularly varied particle sizes and uniform
      distribution. The obtained heterostructures possessed enhanced intrinsic
      peroxidase-like activity, and the activities regularly changed as the sizes of
      ZnFe2O4 nanoparticles varied. The heterostructures were further applied in
      sensitive colorimetric biosensing of urine glucose. 

PMID- 23872668
TI  - A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn's
      disease refractory to biologic therapy.
AB  - BACKGROUND & AIMS: Transplantation of peripheral blood stem cells has been
      successful therapy for small numbers of patients with Crohn's disease (CD), but
      requires prior myeloconditioning. Mesenchymal stromal cells (MSCs) escape immune
      recognition, so myeloconditioning is not required before their administration. We
      investigated the efficacy of allogeneic MSCs in patients with luminal CD.
      METHODS: Our phase 2, open-label, multicenter study included 16 patients (21-55 y
      old; 6 men) with infliximab- or adalimumab-refractory, endoscopically confirmed,
      active luminal CD (CD activity index [CDAI], >250). Subjects were given
      intravenous infusions of allogeneic MSCs (2 * 10(6) cells/kg body weight) weekly
      for 4 weeks. The primary end point was clinical response (decrease in CDAI >100
      points) 42 days after the first MSC administration; secondary end points were
      clinical remission (CDAI, <150), endoscopic improvement (a CD endoscopic index of
      severity [CDEIS] value, <3 or a decrease by >5), quality of life, level of C
      reactive protein, and safety. RESULTS: Among the 15 patients who completed the
      study, the mean CDAI score was reduced from 370 (median, 327; range, 256-603) to
      203 (median, 129) at day 42 (P < .0001). The mean CDAI scores decreased after
      each MSC infusion (370 before administration, 269 on day 7, 240 on day 14, 209 on
      day 21, 182 on day 28, and 203 on day 42). Twelve patients had a clinical
      response (80%; 95% confidence interval, 72%-88%; mean reduction in CDAI, 211;
      range 102-367), 8 had clinical remission (53%; range, 43%-64%; mean CDAI at day
      42, 94; range, 44-130). Seven patients had endoscopic improvement (47%), for whom
      the mean CDEIS scores decreased from 21.5 (range, 3.3-33) to 11.0 (range, 0.3
      18.5). One patient had a serious adverse event (2 dysplasia-associated lesions),
      but this probably was not caused by MSCs. CONCLUSIONS: In a phase 2 study,
      administration of allogeneic MSCs reduced CDAI and CDEIS scores in patients with
      luminal CD refractory to biologic therapy. ClinicalTrials.gov number,
      NCT01090817.

PMID- 23872669
TI  - Patatin-like phospholipase domain-containing protein 3 rs738409-G in recipients
      of liver transplants is a risk factor for graft steatosis.
AB  - BACKGROUND & AIMS: The G-allele in position rs738409 of patatin-like
      phospholipase domain-containing protein 3 (PNPLA3) is associated with an
      increased hepatic concentration of triglyceride and is a risk factor for advanced
      liver disease. We investigated the association of donor and recipient risk
      alleles with the development of graft steatosis after liver transplantation.
      METHODS: PNPLA3 genotypes were determined in 237 transplant recipients and in 255
      organ donors. Macrovesicular steatosis was assessed by unenhanced computed
      tomography 5 years after liver transplantation in 95 patients and correlated with
      donor and recipient PNPLA3 genotype. RESULTS: The risk allele was significantly
      more frequent in transplant recipients than in donors (42% vs 28%; P < .001). A
      prevalence of graft steatosis of 30% or greater significantly increased from
      11.6% at 1 year after liver transplantation to 32.6% at 5 years after
      transplantation. Five years after liver transplantation, steatosis was present in
      63.2% of patients homozygous for the rs738409-G allele, in 31.4% of heterozygous
      recipients, and in 12.0% of rs738409-CC recipients (P = .002). Donor genotypes
      were not associated with the development of graft steatosis. In multivariate
      regression analysis, recipients who carried rs738409-GG had a 13.7-fold higher
      risk of graft steatosis than recipients who carried rs738409-CC (P = .022),
      independent of recipient age, weight gain after liver transplantation, or the
      underlying disease. CONCLUSIONS: Liver transplant recipients who carry rs738409-G
      in PNPLA3 are at increased risk for hepatic triglyceride accumulation,
      independent of the graft PNPLA3 genotype.

PMID- 23872670
TI  - Merging organocatalysis with transition metal catalysis and using O2 as the
      oxidant for enantioselective C-H functionalization of aldehydes.
AB  - A new catalytic Saegusa oxidation-Michael addition cascade reaction has been
      developed for the enantioselective beta-functionalization of aldehydes. The
      feature of this research is the combination of organocatalysis and transition
      metal catalysis for the asymmetric C-H functionalization which remains an
      underdeveloped research topic. 

PMID- 23872671
TI  - 1-Propanol probing methodology: two-dimensional characterization of the effect of
      solute on H2O.
AB  - The wording "hydrophobicity/hydrophilicity" has been used in a loose manner based
      on human experiences. We have devised a more quantitative way to redefine
      "hydrophobes" and "hydrophiles" in terms of the mole fraction dependence pattern
      of one of the third derivative quantities, the enthalpic interaction between
      solute molecules. We then devised a thermodynamic methodology to characterize the
      effect of a solute on H2O in terms of its hydrophobicity and/or hydrophilicity.
      We use a thermodynamic signature, the enthalpic interaction of 1-propanol, H, to
      monitor how the test solute modifies H2O. By this method, characterization is
      facilitated by two indices; one pertaining to its hydrophobicity and the other
      its hydrophilicity. Hence differences among amphiphiles are quantified in a two
      dimensional manner. Furthermore, an individual ion can be characterized
      independent of a counter ion. By using this methodology, we have studied the
      effects on H2O of a number of solutes, and gained some important new insights.
      For example, such commonly used examples of hydrophobes in the literature as
      tetramethyl urea, trimethylamine-N-oxide, and tetramethylammonium salts are in
      fact surprisingly hydrophilic. Hence the conclusions about "hydrophobes" using
      these samples ought to be interpreted with caution. The effects of anions on H2O
      found by this methodology are in the same sequence of the Hofmeister ranking,
      which will no doubt aid a further investigation into this enigma in biochemistry.
      Thus, it is likely that this methodology could play an important role in the
      characterization of the effects of solutes in H2O, and a perspective view may be
      useful. Here, we describe the basis on which the methodology is developed and the
      methodology itself in m.ore detail than given in individual papers. We then
      summarize the results in two dimensional hydrophobicity/hydrophilicity maps. 

PMID- 23872673
TI  - Programmed multiple complexation for the creation of helical structures from
      acyclic phenol-bipyridine oligomer ligands.
AB  - Two new multidentate ligands, H3L(1) and H4L(2), possessing bipyridine-phenol
      repetitive units were designed so that the multi-metal complexation could produce
      a single-helical structure in a pre-programmed fashion. The ligands were
      synthesized by successive palladium-catalyzed coupling reactions. The
      complexation of H3L(1) with zinc(II) and nickel(II) acetate afforded
      [L(1)Zn2(OAc)] and [(L(1))2Ni4](OAc)2, respectively. Each of the ligand moieties
      in these complexes formed a one-turn single helix. The zinc(II) complex
      [L(1)Zn2(OAc)] underwent a helix compression-extension motion in solution. The
      complexation of the H3L(1) ligand with iron(III) chloride gave a dinuclear
      complex [(HL(1))2Fe2Cl2] with a non-helical dimeric structure. The longer ligand
      H4L(2) afforded a trinuclear complex [L(2)Zn3(OAc)2] with a 1.5-turn single
      helical structure upon complexation with zinc(II) acetate. The reaction of the
      H4L(2) ligand with cobalt(II) acetate under aerobic conditions gave a mixed
      valence complex [L(2)Co3(OAc)3(OMe)], which had two trivalent and one divalent
      cobalt ions. The structural features of the trinuclear complexes significantly
      depended on the metals; [L(2)Co3(OAc)3(OMe)] had a helical pitch of 7.6 A, which
      was almost twice that of [L(2)Zn3(OAc)2] (4.0 A).

PMID- 23872674
TI  - Epithelial neutral amino acid transporters: lessons from mouse models.
AB  - PURPOSE OF REVIEW: Epithelial neutral amino acid transporters have been
      identified at the molecular level in recent years. Mouse models have now
      established the crucial role of these transporters for systemic amino acid
      homeostasis. This review summarizes recent progress in this field. RECENT
      FINDINGS: Epithelial neutral amino acid transporters play an important role in
      the homeostasis of neutral amino acid levels in the body. They are important for
      the maintenance of body weight and muscle mass and serve as fuels. They also
      serve a role in providing nutrients to epithelial cells. Changes of plasma amino
      acid levels are not necessarily correlated to the amino acids appearing in the
      urine; changes in organ amino acid metabolism need to be taken into account.
      SUMMARY: Genetic deletion of neutral amino acid transporters provides insight
      into their role in protein nutrition and homeostasis.

PMID- 23872675
TI  - Renal nerves in blood pressure regulation.
AB  - PURPOSE: This review highlights the physiological mechanisms underlying the
      neural regulation of the kidney, normally to maintain cardiovascular homeostasis,
      and in pathophysiological states of hypertension and renal disease. It is
      relevant because of the demonstration that bilateral renal denervation in
      different hypertensive groups causes a sustained reduction in blood pressure.
      RECENT FINDINGS: There are patients groups in whom their hypertension is
      resistant to antihypertensive drugs or with renal diseases in which they are
      contraindicated. Recently, medical devices have been developed to manipulate the
      sympathetic nervous system, for example, implantation of carotid sinus nerve
      stimulating electrodes and ablation of the renal innervation. These approaches
      have been relatively successful but there remains a lack of understanding of the
      neural mechanisms impinging on the kidney that regulate long-term control of
      blood pressure. SUMMARY: The observation that bilateral renal nerve ablation can
      reduce blood pressure represents an important therapeutic milestone. Nonetheless,
      questions arise as to the underlying mechanisms, the long-term consequences,
      whether there may be re-innervation over a number of years, or whether some
      unknown consequence to the denervation may arise. This may point to the
      development of novel compounds targeted to the innervation of the kidney.

PMID- 23872676
TI  - Consumers' misunderstanding of health insurance.
AB  - We report results from two surveys of representative samples of Americans with
      private health insurance. The first examines how well Americans understand, and
      believe they understand, traditional health insurance coverage. The second
      examines whether those insured under a simplified all-copay insurance plan will
      be more likely to engage in cost-reducing behaviors relative to those insured
      under a traditional plan with deductibles and coinsurance, and measures consumer
      preferences between the two plans. The surveys provide strong evidence that
      consumers do not understand traditional plans and would better understand a
      simplified plan, but weaker evidence that a simplified plan would have strong
      appeal to consumers or change their healthcare choices. 

PMID- 23872677
TI  - Special focus CRISPR-Cas.

PMID- 23872678
TI  - Butyrophilin 3A1 binds phosphorylated antigens and stimulates human gammadelta T
      cells.
AB  - Human T cells that express a T cell antigen receptor (TCR) containing gamma-chain
      variable region 9 and delta-chain variable region 2 (Vgamma9Vdelta2) recognize
      phosphorylated prenyl metabolites as antigens in the presence of antigen
      presenting cells but independently of major histocompatibility complex (MHC), the
      MHC class I-related molecule MR1 and antigen-presenting CD1 molecules. Here we
      used genetic approaches to identify the molecule that binds and presents
      phosphorylated antigens. We found that the butyrophilin BTN3A1 bound
      phosphorylated antigens with low affinity, at a stoichiometry of 1:1, and
      stimulated mouse T cells with transgenic expression of a human Vgamma9Vdelta2
      TCR. The structures of the BTN3A1 distal domain in complex with host- or microbe
      derived phosphorylated antigens had an immunoglobulin-like fold in which the
      antigens bound in a shallow pocket. Soluble Vgamma9Vdelta2 TCR interacted
      specifically with BTN3A1-antigen complexes. Accordingly, BTN3A1 represents an
      antigen-presenting molecule required for the activation of Vgamma9Vdelta2 T
      cells. 

PMID- 23872679
TI  - Structural basis of a unique interferon-beta signaling axis mediated via the
      receptor IFNAR1.
AB  - Type I interferons are important in regulating immune responses to pathogens and
      tumors. All interferons are considered to signal via the heterodimeric IFNAR1
      IFNAR2 complex, yet some subtypes such as interferon-beta (IFN-beta) can exhibit
      distinct functional properties, although the molecular basis of this is unclear.
      Here we demonstrate IFN-beta can uniquely and specifically ligate to IFNAR1 in an
      IFNAR2-independent manner, and we provide the structural basis of the IFNAR1-IFN
      beta interaction. The IFNAR1-IFN-beta complex transduced signals that modulated
      expression of a distinct set of genes independently of Jak-STAT pathways.
      Lipopolysaccharide-induced sepsis was ameliorated in Ifnar1(-/-) mice but not
      Ifnar2(-/-) mice, suggesting that IFNAR1-IFN-beta signaling is pathologically
      relevant. Thus, we provide a molecular basis for understanding specific functions
      of IFN-beta. 

PMID- 23872680
TI  - Utility of disease-specific measures and clinical balance tests in prediction of
      falls in persons with multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: The sensory and motor deficits associated with multiple
      sclerosis (MS) contribute to falls with the majority of persons with MS falling
      at least once annually. To appropriately direct treatment, accurate fall
      prediction measures are needed. In this study of community-dwelling individuals
      with MS followed for 12 months, we sought to determine frequency of falls,
      utility of clinical balance tests to predict falls, and accuracy of participants'
      retrospective recall of fall events. METHODS: Independently ambulatory persons
      with MS underwent 5 clinical balance tests including Activities-specific Balance
      Confidence, Berg Balance Scale, Functional Reach, Timed Up and Go, and Dynamic
      Gait Index, and one disease-specific measure of disability (Expanded Disability
      Status Scale) and then were followed for 1 year. Participants were queried
      monthly by phone to determine the number of fall events that had occurred.
      Accuracy of fall prediction was determined by receiver operating characteristic
      curve analysis and comparison of balance test performance between fallers and
      nonfallers. RESULTS: Sixty-one percent of the 38 participants were classified as
      fallers at 12-month follow-up. Only the Berg Balance Scale, Dynamic Gait Index,
      and the Activities-specific Balance Confidence demonstrated clinically useful
      levels of accuracy. In addition, participants were generally poor in their
      accurate recall of fall events relative to their monthly fall reports. DISCUSSION
      AND CONCLUSIONS: The majority of participants fell during a 1-year prospective
      follow-up. Only 2 balance performance measures and 1 balance confidence measure
      accurately distinguished between fallers and nonfallers as well as possessed
      clinically useful levels of sensitivity and specificity. These results also
      emphasized the inaccuracy of retrospective fall history in an MS sample.

PMID- 23872681
TI  - Counting repetitions: an observational study of video game play in people with
      chronic poststroke hemiparesis.
AB  - BACKGROUND AND PURPOSE: The use of video gaming as a therapeutic intervention has
      increased in popularity; however, the number of repetitions in comparison with
      traditional therapy methods has yet to be investigated. The primary purpose of
      this study was to document and compare the number of repetitions performed while
      playing 1 of 2 video gaming systems for a time frame similar to that of a
      traditional therapy session in individuals with chronic stroke. METHODS: Twelve
      participants with chronic stroke (mean age, 66.8 +/- 8.2 years; time poststroke,
      19.2 +/- 15.4 months) completed video game play sessions, using either the
      Nintendo Wii or the Playstation 2 EyeToy. A total of 203 sessions were captured
      on video record; of these, 50 sessions for each gaming system were randomly
      selected for analysis. For each selected record, active upper and lower extremity
      repetitions were counted for a 36-minute segment of the recorded session.
      RESULTS: The Playstation 2 EyeToy group produced an average of 302.5 (228.1)
      upper extremity active movements and 189.3 (98.3) weight shifts, significantly
      higher than the Nintendo Wii group, which produced an average of 61.9 (65.7)
      upper extremity active movements and 109.7 (78.5) weight shifts. No significant
      differences were found in steps and other lower extremity active movements
      between the 2 systems. DISCUSSION AND CONCLUSIONS: The Playstation 2 EyeToy group
      produced more upper extremity active movements and weight shifting movements than
      the Nintendo Wii group; the number and type of repetitions varied across games.
      Active gaming (specifically Playstation 2 EyeToy) provided more upper extremity
      repetitions than those reported in the literature by using traditional therapy,
      suggesting that it may be a modality to promote increased active movements in
      individuals poststroke.

PMID- 23872682
TI  - Concussion: current concepts in diagnosis and management.
AB  - Current understanding of the term "concussion" is fraught with misconceptions
      regarding the extent and nature of brain injury. Despite increasing attention in
      popular media and within the context of sports, considerable gaps exist in our
      knowledge of the diagnosis, underlying brain pathology, recovery of function, and
      optimal interventions for concussion. In this special interest article, we
      discuss the definition and risk factors associated with concussion, summarize and
      highlight some of the most widely used assessment tools, and critique the
      evidence for current principles of concussion management. Our evaluation has
      identified opportunities for novel neuroimaging techniques to improve the
      understanding of the pathophysiology of concussion and to evaluate the changes in
      the recovering brain in response to rehabilitation. In summary, a clear
      definition of the underlying brain pathology, the potential long-term
      consequences, and the risk factors of injury and recovery will help guide future
      research aiming to minimize the impact of injury and develop innovative and
      successful therapeutic approaches aimed at ameliorating the functional
      impairments associated with concussion.

PMID- 23872687
TI  - Incorporating robotic-assisted telerehabilitation in a home program to improve
      arm function following stroke.
AB  - BACKGROUND AND PURPOSE: After stroke, many individuals lack resources to receive
      the intensive rehabilitation that is thought to improve upper extremity motor
      function. This case study describes the application of a telerehabilitation
      intervention using a portable robotic device combined with a home exercise
      program (HEP) designed to improve upper extremity function. CASE DESCRIPTION: The
      participant was a 54-year-old man, 22 weeks following right medullary pyramidal
      ischemic infarct. At baseline, he exhibited residual paresis of the left upper
      extremity, resulting in impaired motor control consistent with a flexion
      synergistic pattern, scoring 22 of 66 on the Fugl-Meyer Assessment. INTERVENTION:
      The participant completed 85 total hours of training (38 hours of robotic device
      and 47 hours of HEP) over the 8-week intervention period. OUTCOMES: The
      participant demonstrated an improvement of 26 points on the Action Research Arm
      Test, 5 points on the Functional Ability Scale portion of the Wolf Motor Function
      Test, and 20 points on the Fugl-Meyer Assessment, all of which surpassed the
      minimal clinically important difference. Of the 17 tasks of the Wolf Motor
      Function Test, he demonstrated improvement on 11 of the 15 time-based tasks and
      both strength measures. The participant reported an overall improvement in his
      recovery from stroke on the Stroke Impact Scale quality-of-life questionnaire
      from 40 of 100 to 65 of 100. His score on the Center for Epidemiologic Studies
      Depression Scale improved by 19 points. DISCUSSION: This case demonstrates that
      robotic-assisted therapy paired with an HEP can be successfully delivered within
      a home environment to a person with stroke. Robotic-assisted therapy may be a
      feasible and efficacious adjunct to an HEP program to elicit substantial
      improvements in upper extremity motor function, especially in those persons with
      stroke who lack access to stroke rehabilitation centers.

PMID- 23872688
TI  - Molecular logistics using cytocleavable polyrotaxanes for the reactivation of
      enzymes delivered in living cells.
AB  - The intracellular delivery of enzymes is an essential methodology to extend their
      therapeutic application. Herein, we have developed dissociable supermolecule
      enzyme polyelectrolyte complexes based on reduction-cleavable cationic
      polyrotaxanes (PRXs) for the reactivation of delivered enzymes. These PRXs are
      characterized by their supramolecular frameworks of a polymeric chain threading
      into cyclic molecules, which can form polyelectrolyte complexes with anionic
      enzymes while retaining their three dimensional structure, although their
      enzymatic activity is reduced. Upon the addition of a reductant, the PRXs
      dissociate into their constituent molecules and release the enzymes, resulting in
      a complete recovery of enzymatic activity. Under the intracellular environment,
      the PRX-based enzyme complexes showed the highest intracellular enzymatic
      activity and efficient activation of anticancer prodrugs to induce cytotoxic
      effects in comparison with the non-dissociable complexes and the commercial cell
      penetrating peptide-based reagents. Thus, the intracellularly dissociable
      supermolecules are an attractive system for delivering therapeutic enzymes into
      living cells. 

PMID- 23872689
TI  - Asystole due to head scratching: a newly confirmed situational syncope.

PMID- 23872690
TI  - Response of right ventricular size to treatment with cardiac resynchronization
      therapy and the risk of ventricular tachyarrhythmias in MADIT-CRT.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is increasingly recognized
      for its ability to reduce ventricular tachyarrhythmias, possibly associated with
      left ventricular reverse remodeling, but the role of the right ventricle (RV) in
      this process has not been examined. OBJECTIVE: The purpose of this study was to
      investigate the relationship between ventricular tachyarrhythmias and change in
      RV dimensions in patients receiving CRT with a defibrillator (CRT-D). METHODS:
      Multivariate Cox proportional hazards regression modeling was used to assess the
      risk for fast (>=180 bpm) ventricular tachycardia/ventricular fibrillation
      (VT/VF) or death by baseline and follow-up RV size (defined as right ventricular
      end-diastolic area [RVEDA]) among 1495 patients enrolled in the Multicenter
      Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy
      (MADIT-CRT). RESULTS: Multivariate analysis showed that treatment with CRT-D was
      independently associated with a 27% (P = .003) reduction in the risk of VT/VF or
      death among patients with larger RVs (>first quartile RVEDA >=13 mm(2)/m(2))
      compared with implantable cardioverter-defibrillator (ICD)-only therapy, whereas
      in patients with smaller RVs there was no significant difference in the risk of
      VT/VF between the 2 treatment arms (hazard ratio = 1.00, P = .99). At 1-year
      follow-up, CRT-D patients displayed significantly greater reductions in RVEDA
      compared to ICD-only patients (P <.001), associated with a corresponding
      reduction in the risk of subsequent VT/VF or death (>first quartile reduction in
      RVEDA with CRT-D vs ICD-only: hazard ratio = 0.55, P <.001) independent of
      changes in left ventricular dimensions. CONCLUSION: Our findings suggest that the
      RV may have an important role in determining the antiarrhythmic effect of CRT
      independent of the effect of the device on the left ventricle.

PMID- 23872691
TI  - Fever-induced Brugada pattern: how common is it and what does it mean?
AB  - BACKGROUND: Fever is known to unmask the Brugada pattern on the electrocardiogram
      (ECG) and trigger ventricular arrhythmias in patients with Brugada syndrome.
      Genetic studies in selected cases with fever-induced Brugada pattern have
      identified disease-causing mutations. Thus, "fever-induced Brugada" is a
      recognized clinical entity. However, its prevalence has not been systematically
      evaluated. OBJECTIVE: The purpose of this study was to assess the prevalence of
      Brugada pattern in consecutive patients with fever. METHODS: ECGs of patients
      with fever admitted to the emergency department were evaluated for the presence
      of Brugada pattern and compared with ECGs of consecutive nonfebrile patients.
      RESULTS: ECGs of 402 patients with fever and 909 without were evaluated. Type I
      Brugada pattern was 20 times more common in the febrile group than in the
      afebrile group (2% vs. 0.1%, respectively, P = .0001). All patients with fever
      induced type I Brugada pattern were asymptomatic and remained so during 30 months
      of follow-up. CONCLUSION: Type I Brugada pattern is definitively more common
      among patients with fever, suggesting that asymptomatic Brugada syndrome is more
      prevalent than previously estimated.

PMID- 23872692
TI  - The phenotype characteristics of type 13 long QT syndrome with mutation in KCNJ5
      (Kir3.4-G387R).
AB  - BACKGROUND: Long QT syndrome type 13 (LQT13) is caused by loss-of-function
      mutation in the KCNJ5-encoded cardiac G-protein-coupled inward rectifier
      potassium channel subtype 4 protein. The electrocardiographic (ECG) features of
      LQT13 are not described yet. OBJECTIVE: To describe for the first time in detail
      the phenotype-genotype relationship of the ECG and clinical features in patients
      with LQT13. METHODS: The 12-lead ECGs, 24-hour Holter recordings, and clinical
      information from KCNJ5-G387R mutation carriers of a fourth-generation Han Chinese
      family with LQT13 and a group of healthy Chinese individuals were analyzed.
      RESULTS: Compared with the analysis of the healthy group (n = 8), age- and sex
      matched pair analysis revealed that the mutation carriers (n = 8) had ventricular
      repolarization abnormality results in the prolongation of corrected QT and QTpeak
      intervals (P < .01); greater combined measure of repolarization morphology (T
      wave morphology combination score) based on asymmetry, flatness, and notch (P <
      .01); and reduced low frequency/high frequency ratio of heart rate variability (P
      < .01) as a reflection of cardiac autonomic imbalance. Mean heart rate, time
      domain parameters of heart rate variability, time interval from T-wave peak to T
      wave end, and T-wave amplitude were similar. CONCLUSIONS: This study demonstrates
      for the first time the ECG features of patients with LQT13. Our data suggest that
      QTpeak intervals and T-wave morphology combination score may be the better
      parameters than the corrected QT interval to predict the phenotype-genotype
      relationship in patients with LQT13.

PMID- 23872694
TI  - Should an improvement in left ventricular systolic function preclude ICD
      generator replacement?

PMID- 23872693
TI  - The QT interval and risk of incident atrial fibrillation.
AB  - BACKGROUND: Abnormal atrial repolarization is important in the development of
      atrial fibrillation (AF), but no direct measurement is available in clinical
      medicine. OBJECTIVE: To determine whether the QT interval, a marker of
      ventricular repolarization, could be used to predict incident AF. METHODS: We
      examined a prolonged QT interval corrected by using the Framingham formula
      (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in
      Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health,
      Aging, and Body Composition (ABC) study were used for validation. Secondary
      predictors included QT duration as a continuous variable, a short QT interval,
      and QT intervals corrected by using other formulas. RESULTS: Among 14,538 ARIC
      study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased
      risk of AF (hazard ratio [HR] 2.05; 95% confidence interval [CI] 1.42-2.96; P <
      .001). No substantive attenuation was observed after adjustment for age, race,
      sex, study center, body mass index, hypertension, diabetes, coronary disease, and
      heart failure. The findings were validated in Cardiovascular Health Study and
      Health, Aging, and Body Composition study and were similar across various QT
      correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was
      associated with an increased unadjusted (HR 1.14; 95% CI 1.10-1.17; P < .001) and
      adjusted (HR 1.11; 95% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a
      short QT interval were inconsistent across cohorts. CONCLUSIONS: A prolonged QT
      interval is associated with an increased risk of incident AF.

PMID- 23872695
TI  - Should an improvement in left ventricular systolic function preclude ICD
      generator replacement?

PMID- 23872696
TI  - Does atrial fibrillation ablation really reduce stroke rates?

PMID- 23872697
TI  - The "nervous" kidney and ventricular fibrillation: a possible game changer?

PMID- 23872698
TI  - One-dimensional alignment of strong Lewis acid sites in a porous coordination
      polymer.
AB  - A new lanthanoid porous coordination polymer, La-BTTc (BTTc = benzene-1,3,5
      tris(2-thiophene-5-carboxylate)), was synthesized and structurally characterized
      to have densely aligned one-dimensional open metal sites, which were found to act
      as strong Lewis acid sites after the removal of the coordinated solvent. 

PMID- 23872699
TI  - A randomised controlled trial of a brief online mindfulness-based intervention.
AB  - OBJECTIVES: There is growing evidence that mindfulness has positive consequences
      for both psychological and physical health in both clinical and non-clinical
      populations. The potential benefits of mindfulness underpin a range of
      therapeutic intervention approaches designed to increase mindfulness in both
      clinical and community contexts. Self-guided mindfulness-based interventions may
      be a way to increase access to the benefits of mindfulness. This study explored
      whether a brief, online, mindfulness-based intervention can increase mindfulness
      and reduce perceived stress and anxiety/depression symptoms within a student
      population. METHOD: One hundred and four students were randomly allocated to
      either immediately start a two-week, self-guided, online, mindfulness-based
      intervention or a wait-list control. Measures of mindfulness, perceived stress
      and anxiety/depression were administered before and after the intervention
      period. RESULTS: Intention to treat analysis identified significant group by time
      interactions for mindfulness skills, perceived stress and anxiety/depression
      symptoms. Participation in the intervention was associated with significant
      improvements in all measured domains, where no significant changes on these
      measures were found for the control group. CONCLUSIONS: This provides evidence in
      support of the feasibility and effectiveness of shorter self-guided mindfulness
      based interventions. The limitations and implications of this study for clinical
      practice are discussed.

PMID- 23872700
TI  - Mechanisms of change in cognitive behaviour therapy for panic disorder: the role
      of panic self-efficacy and catastrophic misinterpretations.
AB  - The efficacy of cognitive behavioural therapy (CBT) for panic disorder with or
      without agoraphobia (PD) is well-established; however, little is known about the
      underlying change processes of clinical improvement during therapy. According to
      cognitive theories, CBT for PD primarily works by changing catastrophic
      misinterpretations of bodily symptoms and panic attacks. However, panic self
      efficacy, i.e. the perceived ability to cope with panic attacks, has also been
      suggested as an important change mechanism in CBT for PD. The aim of the study
      was to investigate if change in catastrophic misinterpretations and panic self
      efficacy mediated change in the level of anxiety during the course of thirteen
      sessions of group CBT for PD. Forty-five participants completed weekly self
      report measures of the possible cognitive mediators and the level of anxiety
      throughout therapy. The results indicated that within-person change in panic self
      efficacy in one session, but not in catastrophic misinterpretations, predicted
      within-person level of anxiety symptoms the following week. However, in a
      reversed analysis, prior change in level of anxiety symptoms also predicted
      change in panic self-efficacy the following session. These results support panic
      self-efficacy as a mediator of change in CBT for PD, although a reciprocal causal
      relationship between panic self-efficacy and level of anxiety seems to be
      implied. 

PMID- 23872701
TI  - Maximizing the efficacy of interoceptive exposure by optimizing inhibitory
      learning: a randomized controlled trial.
AB  - Cognitive-behavioral treatments for panic disorder (PD) emphasize interoceptive
      exposure (IE) to target anxiety sensitivity (AS) but vary considerably in its
      manner of delivery. This randomized controlled trial was conducted to compare the
      efficacy of the low-dose delivery of IE exercises often prescribed in treatment
      protocols to an intensive form of IE hypothesized to optimize inhibitory
      learning. Participants (N = 120) with elevated AS were randomly assigned to one
      of four single-session interventions: (a) low-dose IE as prescribed in Barlow and
      Craske's Panic Control Treatment, (b) low-dose IE without controlled breathing or
      a lengthy between-trial rest period, (c) intensive IE, or (d) expressive writing
      control. Compared to the other conditions, intensive IE produced significantly
      greater reductions in AS and fearful responding to a straw breathing task from
      pretreatment to posttreatment. Maintenance of gains during the follow-up period
      did not differ between conditions. Changes in fear toleration and negative
      outcome expectancies fully mediated the superior efficacy of intensive IE over
      low-dose IE. The two low intensity IE conditions produced particularly high rates
      of fear sensitization on between-trial and outcome variables. The findings
      suggest that the intensive delivery of IE exercises has the potential to improve
      the efficacy of exposure-based treatments for PD.

PMID- 23872702
TI  - Enhancing recovery rates: lessons from year one of IAPT.
AB  - BACKGROUND: The English Improving Access to Psychological Therapies (IAPT)
      initiative aims to make evidence-based psychological therapies for depression and
      anxiety disorder more widely available in the National Health Service (NHS). 32
      IAPT services based on a stepped care model were established in the first year of
      the programme. We report on the reliable recovery rates achieved by patients
      treated in the services and identify predictors of recovery at patient level,
      service level, and as a function of compliance with National Institute of Health
      and Care Excellence (NICE) Treatment Guidelines. METHOD: Data from 19,395
      patients who were clinical cases at intake, attended at least two sessions, had
      at least two outcomes scores and had completed their treatment during the period
      were analysed. Outcome was assessed with the patient health questionnaire
      depression scale (PHQ-9) and the anxiety scale (GAD-7). RESULTS: Data
      completeness was high for a routine cohort study. Over 91% of treated patients
      had paired (pre-post) outcome scores. Overall, 40.3% of patients were reliably
      recovered at post-treatment, 63.7% showed reliable improvement and 6.6% showed
      reliable deterioration. Most patients received treatments that were recommended
      by NICE. When a treatment not recommended by NICE was provided, recovery rates
      were reduced. Service characteristics that predicted higher reliable recovery
      rates were: high average number of therapy sessions; higher step-up rates among
      individuals who started with low intensity treatment; larger services; and a
      larger proportion of experienced staff. CONCLUSIONS: Compliance with the IAPT
      clinical model is associated with enhanced rates of reliable recovery.

PMID- 23872703
TI  - [Transition of care from the perspective of pediatric rheumatology].

PMID- 23872704
TI  - Reaction landscape of a pentadentate N5-ligated Mn(II) complex with O2- and H2O2
      includes conversion of a peroxomanganese(III) adduct to a bis(MU
      oxo)dimanganese(III,IV) species.
AB  - Herein we describe the chemical reactivity of the mononuclear
      [Mn(II)(N4py)(OTf)](OTf) (1) complex with hydrogen peroxide and superoxide.
      Treatment of 1 with one equivalent superoxide at -40  degrees C in MeCN formed
      the peroxomanganese(III) adduct, [Mn(III)(O2)(N4py)](+) (2) in ~30% yield.
      Complex 2 decayed over time and the formation of the bis(MU
      oxo)dimanganese(III,IV) complex, [Mn(III)Mn(IV)(MU-O)2(N4py)2](3+) (3) was
      observed. When 2 was formed in higher yields (~60%) using excess superoxide, the
      [Mn(III)(O2)(N4py)](+) species thermally decayed to Mn(II) species and 3 was
      formed in no greater than 10% yield. Treatment of [Mn(III)(O2)(N4py)](+) with 1
      resulted in the formation of 3 in ~90% yield, relative to the concentration of
      [Mn(III)(O2)(N4py)](+). This reaction mimics the observed chemistry of Mn
      ribonucleotide reductase, as it features the conversion of two Mn(II) species to
      an oxo-bridged Mn(III)Mn(IV) compound using O2(-) as oxidant. Complex 3 was
      independently prepared through treatment of 1 with H2O2 and base at -40  degrees
      C. The geometric and electronic structures of 3 were probed using electronic
      absorption, electron paramagnetic resonance (EPR), magnetic circular dichroism
      (MCD), variable-temperature, variable-field MCD (VTVH-MCD), and X-ray absorption
      (XAS) spectroscopies. Complex 3 was structurally characterized by X-ray
      diffraction (XRD), which revealed the N4py ligand bound in an unusual
      tetradentate fashion.

PMID- 23872705
TI  - BET inhibition as a single or combined therapeutic approach in primary paediatric
      B-precursor acute lymphoblastic leukaemia.
AB  - Paediatric B-precursor ALL is a highly curable disease, however, treatment
      resistance in some patients and the long-term toxic effects of current therapies
      pose the need for more targeted therapeutic approaches. We addressed the
      cytotoxic effect of JQ1, a highly selective inhibitor against the transcriptional
      regulators, bromodomain and extra-terminal (BET) family of proteins, in
      paediatric ALL. We showed a potent in vitro cytotoxic response of a panel of
      primary ALL to JQ1, independent of their prognostic features but dependent on
      high MYC expression and coupled with transcriptional downregulation of multiple
      pro-survival pathways. In agreement with earlier studies, JQ1 induced cell cycle
      arrest. Here we show that BET inhibition also reduced c-Myc protein stability and
      suppressed progression of DNA replication forks in ALL cells. Consistent with c
      Myc depletion and downregulation of pro-survival pathways JQ1 sensitised primary
      ALL samples to the classic ALL therapeutic agent dexamethasone. Finally, we
      demonstrated that JQ1 reduces ALL growth in ALL xenograft models, both as a
      single agent and in combination with dexamethasone. We conclude that targeting
      BET proteins should be considered as a new therapeutic strategy for the treatment
      of paediatric ALL and particularly those cases that exhibit suboptimal responses
      to standard treatment. 

PMID- 23872706
TI  - Lessons from next-generation sequencing analysis in hematological malignancies.
AB  - Next-generation sequencing has led to a revolution in the study of hematological
      malignancies with a substantial number of publications and discoveries in the
      last few years. Significant discoveries associated with disease diagnosis, risk
      stratification, clonal evolution and therapeutic intervention have been generated
      by this powerful technology. As part of the post-genomic era, sequencing analysis
      will likely become part of routine clinical testing and the challenge will
      ultimately be successfully transitioning from gene discovery to preventive and
      therapeutic intervention as part of individualized medicine strategies. In this
      report, we review recent advances in the understanding of hematological
      malignancies derived through genome-wide sequence analysis. 

PMID- 23872707
TI  - Modifying chemotherapy response by targeted inhibition of eukaryotic initiation
      factor 4A.
AB  - Translation is regulated predominantly at the initiation phase by several signal
      transduction pathways that are often usurped in human cancers, including the
      PI3K/Akt/mTOR axis. mTOR exerts unique administration over translation by
      regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric
      complex responsible for recruiting 40S ribosomes (and associated factors) to mRNA
      5' cap structures. Hence, there is much interest in targeted therapies that block
      eIF4F activity to assess the consequences on tumor cell growth and chemotherapy
      response. We report here that hippuristanol (Hipp), a translation initiation
      inhibitor that selectively inhibits the eIF4F RNA helicase subunit, eIF4A,
      resensitizes EMU-Myc lymphomas to DNA damaging agents, including those that
      overexpress eIF4E-a modifier of rapamycin responsiveness. As Mcl-1 levels are
      significantly affected by Hipp, combining its use with the Bcl-2 family
      inhibitor, ABT-737, leads to a potent synergistic response in triggering cell
      death in mouse and human lymphoma and leukemia cells. Suppression of eIF4AI using
      RNA interference also synergized with ABT-737 in murine lymphomas, highlighting
      eIF4AI as a therapeutic target for modulating tumor cell response to
      chemotherapy. 

PMID- 23872708
TI  - Sensitized excited free-radical processes as read-write tools: impact on non
      linear lithographic processes.
AB  - A prefluorescent radical probe in which a 2,2,6,6-tetramethylpiperidine-N-oxyl
      (TEMPO) unit is sensitized with visible light via energy transfer from a tethered
      coumarin dye has been synthesized. The excited TEMPO moiety undergoes hydrogen
      abstraction from a polymer with concomitant functionalization of the polymeric
      matrix; this writing process can be reversed thermally. The fluorescent probes
      can be bleached under high intensity illumination, making these new materials
      suitable for dual-tone lithography with potential applications in sub-diffraction
      lithographic imaging. 

PMID- 23872709
TI  - Hydrated mucilage reduces post-dispersal seed removal of a sand desert shrub by
      ants in a semiarid ecosystem.
AB  - Post-dispersal seed removal by animals can lead to extensive seed loss and thus
      is an important factor in structuring plant communities. However, we know much
      less about post-dispersal seed predation than about other forms of herbivory.
      Mucilage plays many ecological roles in adaptation of plants to diverse
      environments; nevertheless, until now the role of mucilage in ant-mediated seed
      movement remains largely hypothetical. We studied the role of mucilage in seed
      removal of Artemisia sphaerocephala by ants in Mu Us Sandland in Inner Mongolia,
      China. Messor aciculatus was the most active seed predator of Artemisia
      sphaerocephala. Time to first ant collecting (T 1st) of wet intact seeds was
      longest and significantly different from that for dry intact seeds, wet
      demucilaged seeds, and dry demucilaged seeds; number of seeds removed to ant
      nests was lowest for wet intact seeds. After they were collected by ants, 5 % of
      wet intact seeds were dropped during transport. Our results indicate that seed
      mucilage of Artemisia sphaerocephala may play a significant role in post
      dispersal seed removal by (1) making seeds less attractive to ants, thus
      resulting in a delay of collection time; (2) forming a strong bond to soil
      particles, making it difficult for ants to remove seeds; and (3) making seeds
      more likely to be dropped during transport, thereby allowing them to escape from
      predation even after collection by ants. This study demonstrates the importance
      of mucilage in reducing seed removal by ants and thus in anchoring seeds of
      desert plants in the vicinity of mother plants.

PMID- 23872711
TI  - Ultrasensitive fluorescence detection of bleomycin via exonuclease III-aided DNA
      recycling amplification.
AB  - A "signal on" approach for ultrasensitive detection of bleomycin was developed by
      bleomycin-Fe(II) induced hairpin DNA scission to release its loop, which was
      subsequently recycled with the aid of exonuclease III and a probe to amplify the
      detectable fluorescent signal.

PMID- 23872710
TI  - Changing trends in surgery for stress urinary incontinence.
AB  - PURPOSE OF REVIEW: Currently, a number of different stress urinary incontinence
      (SUI) procedures exist. The relatively recent adoption of the midurethral sling
      into clinical practice has changed the surgical management of SUI. This critical
      evaluation of the trends in SUI surgery emphasizes the public health burden of
      SUI surgery, provides insight into modern clinical practice, determines whether
      these trends reflect evidence-based data, and highlights potential areas for
      future research. RECENT FINDINGS: Trends in SUI surgery have shown a rise in the
      use of midurethral mesh slings with a concomitant decrease in retropubic
      procedures. The rates of other types of SUI surgery remain quite low. Although
      the overall rate of slings has increased dramatically, limited population-based
      data exist regarding specific types of midurethral slings, such as retropubic vs.
      transobturator vs. mini-slings. There is a need for continued evaluation of these
      trends in response to heightened public awareness of the potential risks of
      synthetic mesh. SUMMARY: The midurethral sling has become the gold standard
      surgery for SUI. It will be important to evaluate future trends in SUI surgery
      given the dynamic changes in new techniques for midurethral slings and long-term
      evidence regarding the effectiveness and risks of specific sling types.

PMID- 23872712
TI  - Vitrigel-eye irritancy test method using HCE-T cells.
AB  - We previously reported that the time-dependent relative changes of
      transepithelial electrical resistance (TEER) after exposing four different
      chemicals to a human corneal epithelium (HCE) model were well correlated to the
      potential of ocular irritancy. Meanwhile, we recently developed a collagen
      vitrigel membrane (CVM) chamber possessing a scaffold composed of high-density
      collagen fibrils equivalent to connective tissues in vivo as a three-dimensional
      culture tool. The CVM chamber is useful for biomedical assays and immunohistology
      using cryosections that are inappropriate to be performed using the conventional
      Millicell chamber with a polyethylene terephthalate membrane. In this study, we
      aimed to develop a new eye irritancy test (EIT) method called "Vitrigel-EIT
      method" that can facilitate to briefly and accurately estimate the widespread
      irritancy of test chemicals by applying the TEER assay system to a HCE model
      fabricated in the CVM chamber. HCE-T cells (a HCE-derived cell strain) were
      cultured in the CVM chamber for 6 days, and consequently, the Vitrigel-HCE model
      possessing the following characteristics of HCE in vivo was formed: six cell
      layers with specific protein expressions and their barrier function. Time
      dependent profiles of TEER values after exposing 30 test chemicals to the HCE
      model were converted into the scores of three indexes (time lag, intensity, and
      plateau level), and each chemical was successfully classified into irritant or
      nonirritant category by utilizing the criteria for the indexes, resulting in the
      excellent correlation with Globally Harmonized System of Classification and
      Labelling of Chemicals (GHS) classification (sensitivity: 100%, specificity: 75%,
      accuracy: 90%). These data suggest that the widespread eye irritancy of chemicals
      can be predicted without false negatives by the Vitrigel-EIT method.
      Interestingly, the disruption of tight junctions was immunohistologically
      observed after exposing not only irritants but also three compounds classified as
      nonirritant by GHS but found positive in our Vitrigel-EIT method confirming a
      possible mild irritant property. 

PMID- 23872713
TI  - Pan-FGFR inhibition leads to blockade of FGF23 signaling, soft tissue
      mineralization, and cardiovascular dysfunction.
AB  - The fibroblast growth factor receptors (FGFR) play a major role in angiogenesis
      and are desirable targets for the development of therapeutics. Groups of Wistar
      Han rats were dosed orally once daily for 4 days with a small molecule pan-FGFR
      inhibitor (5mg/kg) or once daily for 6 days with a small molecule MEK inhibitor
      (3mg/kg). Serum phosphorous and FGF23 levels increased in all rats during the
      course of the study. Histologically, rats dosed with either drug exhibited
      multifocal, multiorgan soft tissue mineralization. Expression levels of the
      sodium phosphate transporter Npt2a and the vitamin D-metabolizing enzymes Cyp24a1
      and Cyp27b1 were modulated in kidneys of animals dosed with the pan-FGFR
      inhibitor. Both inhibitors decreased ERK phosphorylation in the kidneys and
      inhibited FGF23-induced ERK phosphorylation in vitro in a dose-dependent manner.
      A separate cardiovascular outcome study was performed to monitor hemodynamics and
      cardiac structure and function of telemetered rats dosed with either the pan-FGFR
      inhibitor or MEK inhibitor for 3 days. Both compounds increased blood pressure
      (~+ 17 mmHg), decreased heart rate (~-75 bpm), and modulated echocardiography
      parameters. Our data suggest that inhibition of FGFR signaling following
      administration of either pan-FGFR inhibitor or MEK inhibitor interferes with the
      FGF23 pathway, predisposing animals to hyperphosphatemia and a tumoral calcinosis
      like syndrome in rodents. 

PMID- 23872714
TI  - Epigenetic modifications of DAPK and p16 genes contribute to arsenic-induced skin
      lesions and nondermatological health effects.
AB  - Over 26 million people in West Bengal, India, are exposed to very high levels of
      arsenic through drinking water, leading to several deleterious endpoints
      including cancers. To elucidate the role of promoter methylation in arsenic
      induced dermatological and nondermatological health effects, methylation status
      of p16 and DAPK genes was determined. A case-control study was conducted
      involving 72 individuals with arsenic-induced skin lesions (cases) and 50
      individuals without skin lesions (controls), having similar arsenic exposure
      through drinking water. Methylation status was determined by bisulfite conversion
      of genomic DNA and methylation-specific PCR. Expression of the genes was
      determined by real-time PCR and Western blot analysis. Associations between the
      promoter methylation status and nondermatological health effects were determined
      from epidemiological survey data. Significant hypermethylation was found in the
      promoters of both DAPK and p16 genes in the cases compared with the controls
      resulting in downregulation of both the genes in the cases. There was a 3.4-fold
      decrease in the expression of death-associated protein kinase and 2.2-fold
      decrease in gene expression of p16 in the cases compared to the controls, the
      lowest expression being in the cancer tissues. Promoter hypermethylation of the
      genes was also associated with higher risk of developing arsenic-induced skin
      lesions, peripheral neuropathy, ocular and respiratory diseases. This study for
      the first time makes an attempt to correlate epigenetic modifications of the
      tumor suppressor genes with dermatological and nondermatological health outcomes
      in a population chronically exposed to arsenic. 

PMID- 23872716
TI  - A risk calculator for short-term morbidity and mortality after hip fracture
      surgery.
AB  - OBJECTIVE: Hip fractures are a common source of morbidity and mortality among the
      elderly. Although multiple prior studies have identified risk factors for poor
      outcomes, few studies have presented a validated risk stratification calculator.
      METHODS: The American College of Surgeons National Surgical Quality Improvement
      Program database was used to identify 4331 patients undergoing surgery for hip
      fracture between 2005 and 2010. Patient demographics, comorbidities, laboratory
      values, and operative characteristics were compared in a univariate analysis, and
      a multivariate logistic regression analysis was then used to identify independent
      predictors of 30-day morbidity and mortality. Weighted values were assigned to
      each independent risk factor and used to create predictive models of 30-day
      morbidity, minor complication risk, major complication risk, and total
      complication risk. The models were internally validated with randomly partitioned
      80%/20% cohort groups. RESULTS: Thirty-day mortality was 5.9% and morbidity was
      30.0%. Patient age, especially age greater than 80 years [mortality: odds ratio
      (OR): 2.41, 95% confidence interval (CI): 1.17-4.99); morbidity: OR: 1.43, 95%
      CI: 1.05-1.94], and male gender (mortality: OR: 2.28, 95% CI: 1.61-3.22;
      morbidity: OR: 1.26, 95% CI: 1.03-1.54) were associated with both increased
      mortality and morbidity. An increased American Society of Anesthesia class had
      the highest negative impact on total complication incidence in the scoring
      models. Additionally, complete functional dependence, active malignancy, patient
      race, cardiopulmonary disease, laboratory derangements, prolonged operating time,
      and open versus percutaneous surgery independently influenced outcomes. Risk
      scores, based on weighted models, which included the aforementioned variables,
      predicted mortality (P < 0.001, C index: 0.702) and morbidity (P < 0.001, C
      index: 0.670) after hip fracture surgery. CONCLUSIONS: In this study, we have
      developed an internally validated method for risk stratifying patients undergoing
      hip fracture surgery, and this model is predictive of both 30-day morbidity and
      mortality. Our model could be useful for identifying high-risk individuals, for
      obtaining informed consent, and for risk-adjusted comparisons of outcomes between
      institutions. LEVEL OF EVIDENCE: Prognostic level II. See instructions for
      authors for a complete description of levels of evidence.

PMID- 23872717
TI  - Virus infection of a weed increases vector attraction to and vector fitness on
      the weed.
AB  - Weeds are important in the ecology of field crops, and when crops are harvested,
      weeds often become the main hosts for plant viruses and their insect vectors. Few
      studies, however, have examined the relationships between plant viruses, vectors,
      and weeds. Here, we investigated how infection of the weed Datura stramonium L.
      by tomato yellow leaf curl virus (TYLCV) affects the host preference and
      performance of the TYLCV vector, Bemisia tabaci (Gennadius) Q. The results of a
      choice experiment indicated that B. tabaci Q preferentially settled and
      oviposited on TYLCV-infected plants rather than on healthy plants. In addition,
      B. tabaci Q performed better on TYLCV-infected plants than on healthy plants.
      These results demonstrate that TYLCV is indirectly mutualistic to B. tabaci Q.
      The mutually beneficial interaction between TYLCV and B. tabaci Q may help
      explain the concurrent outbreaks of TYLCV and B. tabaci Q in China. 

PMID- 23872715
TI  - Thymic stromal lymphopoietin-elicited basophil responses promote eosinophilic
      esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease
      characterized by esophageal eosinophilia. Current management strategies for EoE
      are nonspecific, and thus there is a need to identify specific immunological
      pathways that could be targeted to treat this disease. EoE is associated with
      polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a
      cytokine that promotes allergic inflammation, but how TSLP might contribute to
      EoE disease pathogenesis has been unclear. Here, we describe a new mouse model of
      EoE-like disease that developed independently of IgE, but was dependent on TSLP
      and basophils, as targeting TSLP or basophils during the sensitization phase
      limited disease. Notably, therapeutic TSLP neutralization or basophil depletion
      also ameliorated established EoE-like disease. In human subjects with EoE, we
      observed elevated TSLP expression and exaggerated basophil responses in
      esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with
      increased basophil responses in patients with EoE. Together, these data suggest
      that the TSLP-basophil axis contributes to the pathogenesis of EoE and could be
      therapeutically targeted to treat this disease. 

PMID- 23872718
TI  - Changes of inhibitory receptors on NK-92 cells and HLA-G on BeWo cells with
      Toxoplasma gondii infection.
AB  - The aim of this study were to demonstrate the effects of Yellow fluorescent
      protein-Toxoplasma gondii infection on the NK-92 cells co-cultured with BeWo
      cells in vitro and to verify the implications upon adverse pregnancy outcome.
      There are four groups including NK-92 cells infected or uninfected with T.
      gondii, and NK-92 cells co-cultured with BeWo cells in the presence or absent of
      T. gondii infection. Cells were observed by fluorescence microscope at 12, 24,
      36, 48, and 60 h after infection. Levels of inhibitory receptors killer
      immunoglobulin-like receptor (KIR)2DL4 and ILT-2 expressed on NK-92 cells, and
      their common ligand HLA-G expressed on BeWo cells were measured by real-time PCR
      and flow cytometry in all groups. Levels of KIR2DL4, ILT-2 and HLA-G increased at
      12, 24, 36, and 48 h, while decreased at 60 h in all T. gondii-infected groups
      compared with their parallel control groups, respectively. KIR2DL4 and ILT-2
      expression in co-culture groups with infection were higher than those in infected
      NK-92 groups at 12, 24, 36, and 48 h, while there were no significant differences
      at 60 h. The expression of the two inhibitory receptors was correlated with HLA-G
      expression in infected co-culture groups. The changes of inhibitory receptors on
      NK-92 cells and their common ligand HLA-G on BeWo cells with T. gondii infection
      might contribute to the occurrence of adverse pregnancy outcome.

PMID- 23872720
TI  - Sivelestat prevents cytoskeletal rearrangements in neutrophils resulting from
      lung re-expansion following one-lung ventilation during thoracic surgery.
AB  - Patients undergoing lobectomy are at risk of developing acute lung injury
      resulting from one-lung ventilation (OLV) during surgery. We investigated the
      morphological and functional behavior of neutrophils in patients who underwent
      lobectomy and assessed the ability of sivelestat to inhibit neutrophil activity.
      This was a blinded randomized study. Sixteen patients who underwent lobectomy
      were given intravenous sivelestat (n = 8) or intravenous saline (n = 8). We
      studied the cytoskeletal rearrangements of circulating neutrophils by determining
      the localization of filamentous actin (F-actin). Pulmonary oxygenation was
      evaluated by measuring the partial pressure of arterial oxygen. We found that the
      number of circulating, F-actin-rimmed neutrophils increased during OLV and after
      lung re-expansion. Our results suggest that, in addition to the surgical
      procedure and OLV, re-expansion of the remaining lung after lobectomy increases
      the neutrophil activation levels. Furthermore, administration of sivelestat
      limited neutrophil activation and improved pulmonary oxygenation in our patients.

PMID- 23872719
TI  - Antihyperalgesic and anti-inflammatory effects of atorvastatin in chronic
      constriction injury-induced neuropathic pain in rats.
AB  - Atorvastatin is a 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor used
      in treatment of hypercholesterolemia and prevention of coronary heart disease.
      The aim of this study is to investigate the antihyperalgesic and anti
      inflammatory effects of atorvastatin (3, 10, and 30 mg/kg by oral gavages for 14
      days) in chronic constriction injury (CCI) model of neuropathic pain in rats. CCI
      caused significant increase in tumor necrosis factor-alpha, interleukin 1 beta,
      prostaglandin E2, along with matrix metalloproteases (MMP-2) and nerve growth
      factor (NGF) levels in sciatic nerve and spinal cord concomitant with mechanical
      and thermal hyperalgesia, which were significantly reduced by oral administration
      of atorvastatin for 14 days as compared to CCI rats. Our study demonstrated that
      atorvastatin attenuates neuropathic pain through inhibition of cytokines, MMP-2,
      and NGF in sciatic nerve and spinal cord suggesting that atorvastatin could be an
      additional therapeutic strategy in management of neuropathic pain.

PMID- 23872721
TI  - Reactive oxygen species in peripheral blood and sputum neutrophils during
      bacterial and nonbacterial acute exacerbation of chronic obstructive pulmonary
      disease.
AB  - Chronic airway inflammation can be mediated by an enhanced neutrophil oxidative
      burst. However, the role of bacteria in the pathogenesis of chronic obstructive
      pulmonary disease (COPD) exacerbations is highly controversial. The aim of this
      study was to evaluate the production of reactive oxygen species (ROS) in
      peripheral blood and sputum neutrophils during bacterial and nonbacterial acute
      exacerbations of COPD (AECOPD). A total of 40 patients with AECOPD, 10 healthy
      nonsmokers, and 10 "healthy" smokers were enrolled into the study. Peripheral
      blood and sputum samples were obtained during exacerbation and after recovery.
      Neutrophils were isolated by high-density gradient centrifugation and magnetic
      separation. ROS production by neutrophils was investigated after stimulation with
      phorbol-myristate-acetate and Staphylococcus aureus bacteria. ROS production by
      neutrophils was assessed as the mean fluorescent intensity using a flow
      cytometer. IL-8 levels in serum and induced sputum were determinant by ELISA.
      Spontaneous ROS production was significantly higher in neutrophils from the
      patients with bacterial AECOPD as compared with nonbacterial AECOPD and stable
      COPD (P <0.05). ROS production stimulated with PMA and with Staphylococcus aureus
      was significantly higher in neutrophils isolated from the patients with bacterial
      AECOPD as compared with nonbacterial and stable COPD (P <0.05). The serum and
      induced sputum IL-8 levels were significantly increased in the patients with
      bacterial AECOPD than nonbacterial AECOPD, stable COPS, and "healthy" smokers and
      nonsmokers (P <0.05) and higher in the induced sputum as the compared with serum
      in all studied groups (P <0.05). Enlarge CRP level was documented during AECOPD
      than in all other groups (P <0.05). A markedly increased ROS production in sputum
      neutrophils during bacterial AECOPD shows an inflammatory response reflecting
      enhanced local inflammation, which can be mediated by bacterial colonization.

PMID- 23872722
TI  - Serum soluble triggering receptor on myeloid cells-1 (sTREM-1) is elevated in
      systemic lupus erythematosus but does not distinguish between lupus alone and
      concurrent infection.
AB  - We sought to determine serum triggering receptor expressed on myeloid cell-1
      (sTREM-1) level in a cohort of patients with systemic lupus erythematosus (SLE).
      Serum sTREM-1 level of 98 patients with SLE and 49 healthy controls was assayed
      by ELISA. Serum sTREM-1 level was significantly elevated in a cohort of 78
      unselected consecutively recruited patients with SLE (mean 1.1 +/- 2.8 rhog/ml,
      median 0.02 rhog/ml) compared to that of the controls (mean 0.11 +/- 0.3 rhog/ml,
      median 0 rhog/ml; p < 0.0001). We also determined serum sTREM-1 level of 20 SLE
      patients with a concurrent infection (mean 0.6 +/- 1.1 rhog/ml, median 0.12
      rhog/ml) and found it not statistically significant compared with that of the
      patients without infection. Serum sTREM-1 level did not correlate with SLE
      disease activity. Our finding of elevated serum sTREM-1 level suggests an
      increased shedding of TREM-1 in SLE and a possible novel pathway of innate immune
      response in autoimmunity.

PMID- 23872723
TI  - Anti-inflammatory effect of auraptene extracted from trifoliate orange (Poncirus
      trifoliate) on LPS-stimulated RAW 264.7 cells.
AB  - Poncirus trifoliate is a traditional Chinese medicinal plant used for treating
      inflammation-related diseases for a long time and trifoliate orange contains
      abundant auraptene. The present study was to evaluate auraptene as a potential
      anti-inflammatory agent and investigate the mechanism of auraptene against
      prostaglandins E2 (PGE2) and cyclooxygenase-2 (COX-2) on lipopolysaccharide (LPS)
      stimulated RAW 264.7 cells by comparing it with aspirin as a positive control
      group. The methods of enzyme-linked immunosorbent assay, reverse transcriptive
      polymerase chain reaction, real-time PCR, and western-blotting were used in the
      study. The results showed that auraptene exhibited better biocompatibility and
      lower cytotoxicity. At the same time, it significantly inhibited the production
      of PGE2 on LPS-stimulated macrophage cells. The auraptene-treated group had a
      higher COX-2 mRNA expression but relatively lower COX-2 protein level which
      implied that auraptene suppressed the post-transcriptional expression of COX-2
      protein but not the transcriptional process. Compared with aspirin, the lower
      cytotoxicity of auraptene can make it a potential source for medicine that can
      benefit patients who are suffering from chronic inflammatory diseases and need
      long-term medication. 

PMID- 23872724
TI  - Orthorhombic C32: a novel superhard sp3 carbon allotrope.
AB  - Using a recently developed 'Crystal structure AnaLYsis by Particle Swarm
      Optimization' (CALYPSO) algorithm on a structural search, we predicted a novel
      sp(3) carbon allotrope possessing an orthorhombic lattice with the space group
      Cmmm (oC32). The calculated elastic constants and the simulated hardness revealed
      that oC32 simultaneously possesses ultra-incompressible and superhard properties
      with a high bulk modulus of 457 GPa and a high Vickers hardness of 96.2 GPa. This
      oC32 phase is dynamically stable and energetically more preferable than the
      experientially observed cold-compressed carbon, thus oC32 is expected to be
      experimentally synthesizable under extreme conditions. These results further
      expand the list of meta-stable carbon allotropes and superhard materials under
      atmospheric and extreme conditions. 

PMID- 23872725
TI  - Mono- and di-nuclear photoluminescent complexes of zinc(II), cadmium(II) and
      mercury(II) of a chiral diimine ligand.
AB  - Reaction of alpha-pyridoin and N-phenyl-o-phenylenediamine affords 2-(2
      (phenylamino)phenylimino)-1,2-di(pyridin-2-yl)ethanol (L) which undergoes
      cyclization to a chiral diimine, 2-methoxy-1-phenyl-2,3-di(pyridin-2-yl)-1,2
      dihydroquinoxaline, L(OMe) (conjugated 14pie system) in the presence of zinc(II),
      cadmium(II) and mercury(II) ions affording [Zn(L(OMe))Cl2] (1), [Cd2(L(OMe))2Cl4]
      (2) and [Hg2(L(OMe))2Cl4] (3) complexes. Ligand L and complexes 1-3 are
      substantiated by elemental analyses, mass, IR, (1)H NMR and UV-vis spectra
      including the single-crystal X-ray structures of 1 and 3. The possibility of the
      atropisomerism of L is restricted in cyclic L(OMe). L and complexes 1-3 are
      fluorescent in fluid solutions at 298 K (CH2Cl2: 1, lambda(ex) = 470 nm,
      lambda(em) = 627 nm, Phi = 0.014, tau(avg) = 2.5 ns; 2, lambda(ex) = 430 nm,
      lambda(em) = 599 nm, Phi = 0.08, tau(avg) = 7.6 ns; 3, lambda(ex) = 415 nm,
      lambda(em) = 600 nm, Phi = 0.021, tau(avg) = 2.8 ns). Time-resolved emission
      spectra (TRES) established that the two-component lifetimes of 1-3 are due to the
      existence of two conformers. Density functional theory (DFT) and time dependent
      (TD) DFT calculations authenticated that 1-3 complexes are fluorescent due to
      intra-ligand charge transfer (ILCT) to the pi(diimines)* orbital.

PMID- 23872726
TI  - Palladium-catalyzed para-selective arylation of phenols with aryl iodides in
      water.
AB  - Highly para-selective palladium-catalyzed direct arylation of phenols with aryl
      iodides was demonstrated by taking advantage of the formal inverse direct
      arylation strategy. A series of 4-aryl phenols were synthesised by employing
      water as a "green" solvent under mild reaction conditions. 

PMID- 23872727
TI  - Management of acquired cholesteatoma in the pediatric population.
AB  - PURPOSE OF REVIEW: This review focuses on the most recent literature pertaining
      to pediatric acquired cholesteatoma and aims to integrate findings into a
      comprehensive management approach. RECENT FINDINGS: Pediatric acquired
      cholesteatoma has been shown to differ from the adult variety secondary to
      anatomy and physiologic factors. Whereas the goals of therapeutic management are
      ultimately similar in adult and pediatric patients, special considerations must
      be taken into account when deciding on a treatment plan for a child. Although
      avoidance of an unstable mastoid cavity is an important consideration in this
      population, successful management has been reported with canal wall-up, canal
      wall-down, and hybrid techniques. Second-look procedures are also important when
      concern of recurrence exists. Newer innovations include endoscopic ear surgery
      and diffusion-weighted imaging. SUMMARY: The principal goal of pediatric
      cholesteatoma management is eradication of disease. An individualized approach is
      paramount in yielding superior results in these patients. Special consideration
      should be given to anatomical and social factors.

PMID- 23872728
TI  - Use of mastoid obliteration techniques in cholesteatoma.
AB  - PURPOSE OF REVIEW: To evaluate the choice of techniques, safety and long-term
      outcome of mastoid obliteration and assess the place of imaging in the
      postoperative monitoring of residual cholesteatoma. RECENT FINDINGS: All recent
      reports on mastoid obliteration for the management of cholesteatoama were
      favourable. Long-term follow-up reports did not show problems arising from hidden
      cholesteatoma, even for the paediatric population. Non-EPI DW MR imaging has
      shown great promise in detecting residual cholesteatoma in obliterated cavities.
      SUMMARY: Canal wall down technique with primary mastoid obliteration for
      cholesteatoma has low recurrent and residual cholesteatoma rates. Most ears
      remained dry and waterproof on long-term follow-up.

PMID- 23872729
TI  - FRET-based characterisation of surfactant bilayer protected core-shell carbon
      nanoparticles: advancement toward carbon nanotechnology.
AB  - Surfactant bilayer protected core-shell carbon nanoparticles (CNPs) have been
      synthesised. Forster resonance energy transfer (FRET) between the core-shell CNPs
      and two strategically chosen organic dyes has been exploited to characterise the
      protective surfactant bilayer. 

PMID- 23872730
TI  - The effect of particle proximity on the oxygen reduction rate of size-selected
      platinum clusters.
AB  - The diminished surface-area-normalized catalytic activity of highly dispersed Pt
      nanoparticles compared with bulk Pt is particularly intricate, and not yet
      understood. Here we report on the oxygen reduction reaction (ORR) activity of
      well-defined, size-selected Pt nanoclusters; a unique approach that allows
      precise control of both the cluster size and coverage, independently. Our
      investigations reveal that size-selected Pt nanoclusters can reach
      extraordinarily high ORR activities, especially in terms of mass-normalized
      activity, if deposited at high coverage on a glassy carbon substrate. It is
      observed that the Pt cluster coverage, and hence the interparticle distance,
      decisively influence the observed catalytic activity and that closely packed
      assemblies of Pt clusters approach the surface activity of bulk Pt. Our results
      open up new strategies for the design of catalyst materials that circumvent the
      detrimental dispersion effect, and may eventually allow the full electrocatalytic
      potential of Pt nanoclusters to be realized. 

PMID- 23872731
TI  - Effect of airborne contaminants on the wettability of supported graphene and
      graphite.
AB  - It is generally accepted that supported graphene is hydrophobic and that its
      water contact angle is similar to that of graphite. Here, we show that the water
      contact angles of freshly prepared supported graphene and graphite surfaces
      increase when they are exposed to ambient air. By using infrared spectroscopy and
      X-ray photoelectron spectroscopy we demonstrate that airborne hydrocarbons adsorb
      on graphitic surfaces, and that a concurrent decrease in the water contact angle
      occurs when these contaminants are partially removed by both thermal annealing
      and controlled ultraviolet-O3 treatment. Our findings indicate that graphitic
      surfaces are more hydrophilic than previously believed, and suggest that
      previously reported data on the wettability of graphitic surfaces may have been
      affected by unintentional hydrocarbon contamination from ambient air. 

PMID- 23872732
TI  - User-interactive electronic skin for instantaneous pressure visualization.
AB  - Electronic skin (e-skin) presents a network of mechanically flexible sensors that
      can conformally wrap irregular surfaces and spatially map and quantify various
      stimuli. Previous works on e-skin have focused on the optimization of pressure
      sensors interfaced with an electronic readout, whereas user interfaces based on a
      human-readable output were not explored. Here, we report the first user
      interactive e-skin that not only spatially maps the applied pressure but also
      provides an instantaneous visual response through a built-in active-matrix
      organic light-emitting diode display with red, green and blue pixels. In this
      system, organic light-emitting diodes (OLEDs) are turned on locally where the
      surface is touched, and the intensity of the emitted light quantifies the
      magnitude of the applied pressure. This work represents a system-on-plastic
      demonstration where three distinct electronic components--thin-film transistor,
      pressure sensor and OLED arrays--are monolithically integrated over large areas
      on a single plastic substrate. The reported e-skin may find a wide range of
      applications in interactive input/control devices, smart wallpapers, robotics and
      medical/health monitoring devices.

PMID- 23872734
TI  - Variation in leaf and twig CO2 flux as a function of plant size: a comparison of
      seedlings, saplings and trees.
AB  - Rates of tissue-level function have been hypothesized to decline as trees grow
      older and larger, but relevant evidence to assess such changes remains limited,
      especially across a wide range of sizes from saplings to large trees. We measured
      functional traits of leaves and twigs of three cold-temperate deciduous tree
      species in Minnesota, USA, to assess how these vary with tree height. Individuals
      ranging from 0.13 to 20 m in height were sampled in both relatively open and
      closed canopy environments to minimize light differences as a potential driver of
      size-related differences in leaf and twig properties. We hypothesized that (H1)
      gas-exchange rates, tissue N concentration and leaf mass per unit area (LMA)
      would vary with tree size in a pattern reflecting declining function in taller
      trees, yet maintaining (H2) bivariate trait relations, common among species as
      characterized by the leaf economics spectrum. Taking these two ideas together
      yielded a third, integrated hypothesis that (H3) nitrogen (N) content and gas
      exchange rates should decrease monotonically with tree size and LMA should
      increase. We observed increasing LMA and decreasing leaf and twig Rd with
      increasing size, which matched predictions from H1 and H3. However, opposite to
      our predictions, leaf and twig N generally increased with size, and thus had
      inverse relations with respiration, rather than the predicted positive relations.
      Two exceptions were area-based leaf N of Prunus serotina Ehrh. in gaps and mass
      based leaf N of Quercus ellipsoidalis E. J. Hill in gaps, both of which showed
      qualitatively hump-shaped patterns. Finally, we observed hump-shaped
      relationships between photosynthetic capacity and tree height, not mirroring any
      of the other traits, except in the two cases highlighted above. Bivariate trait
      relations were weak intra-specifically, but were generally significant and
      positive for area-based traits using the pooled dataset. Results suggest that
      different traits vary with tree size in different ways that are not consistent
      with a universal shift towards a lower 'return on investment' strategy. Instead,
      species traits vary with size in patterns that likely reflect complex variation
      in water, light, nitrogen and carbon availability, storage and use.

PMID- 23872733
TI  - A novel Mcl1 variant inhibits apoptosis via increased Bim sequestration.
AB  - Members of the Bcl-2 protein family are frequently deregulated in tumors as they
      critically control cell death induction in mammalian cells. Alterations of these
      proteins may cause resistance to chemotherapy-induced cell death and immune
      responses. By serendipity we cloned a variant of the anti-apoptotic Bcl2-family
      member Myeloid cell leukemia-1 (Mcl1) from human neuroblastoma and leukemia
      cells. This Mcl1L variant lacks a 45 bp sequence that codes for 15 highly
      conserved amino acids ranging from Gly158 to Asp172. This region is part of the
      so called PEST-sequence of Mcl1L and contains two phosphorylation sites (Ser159
      and Thr163) that regulate Mcl1L stability. A caspase 3/caspase 8 cleavage site at
      Asp157 which has been reported to be critical for death-receptor-induced
      apoptosis and for the conversion of Mcl1L into a pro-apoptotic protein is also
      missing in this novel variant. Importantly, Mcl1LdelGly158-Asp172 bound
      significantly more pro-apoptotic Bim compared to Mcl1L and showed increased anti
      proliferative and anti-apoptotic activity compared to Mcl1L during death receptor
      induced cell death. This suggests that this novel Mcl1L variant efficiently
      protects tumor cells against extrinsic death signalling and therefore may provide
      a survival advantage for highly aggressive tumors. 

PMID- 23872735
TI  - Hepatic and hippocampus iron status is not altered in response to increased serum
      ceruloplasmin and serum "free" copper in Wistar rat model for non-Wilsonian brain
      copper toxicosis.
AB  - Copper and iron dyshomeostasis has been implicated directly or indirectly in the
      pathogenesis of neurodegenerative diseases. Previously, we have shown the first
      in vivo evidence of significant increase in the hippocampus copper and zinc
      content with spatial memory impairments, astrocytes swelling (Alzheimer type-II
      cells) coupled with increase in the number of astrocytes, copper deposition in
      the choroid plexus, and degenerated neurons in copper-intoxicated Wistar rats. In
      continuation with our previous study, the aim of this study was to further
      investigate the effects of intraperitoneally injected copper lactate (0.15 mg
      Cu/100 g body weight) daily for 90 days on serum "free" copper levels, iron
      levels in the liver, and hippocampus by atomic absorption spectrophotometry and
      histopathological study of the liver and brain tissues of Wistar rats using
      Perls' Prussian blue (PPB) stain. A massive significant increase in serum "free"
      copper (79.48% increase) along with strong correlation (r = 0.978) was found
      between serum copper and serum "free" copper in copper-intoxicated rats. No
      significant difference was detected in hepatic and hippocampus iron levels
      between control and copper-intoxicated rats. PPB stain demonstrated very few
      scattered grade 1 haemosiderin deposits within sinusoidal cells predominantly
      Kupffer cells; however, brain sections were negatively stained with PPB stain. In
      conclusion, the current study demonstrates that chronic copper toxicity causes
      increase in serum "free" copper, which may serve as predisposing factor for the
      development of neurodegeneration and memory deficits, and grade 1 haemosiderin
      deposition in Kupffer cells without altering hepatic and hippocampus iron levels
      in male Wistar rats.

PMID- 23872736
TI  - Effect of Bacopa monniera extract on methylmercury-induced behavioral and
      histopathological changes in rats.
AB  - Methylmercury (MeHg) is a well-recognized environmental contaminant with
      established health risk to human beings by fish and marine mammal consumption.
      Bacopa monniera (BM) is a perennial herb and is used as a nerve tonic in
      Ayurveda, a traditional medicine system in India. This study was aimed to
      evaluate the effect of B. monniera extract (BME) on MeHg-induced toxicity in rat
      cerebellum. 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) 1 h prior to the administration of MeHg for 21 days.
      After treatment period, MeHg exposure significantly decreases the body weight and
      also caused the following behavioral changes. Decrease tail flick response,
      longer immobility time, significant decrease in motor activity, and spatial short
      term memory. BME pretreatment reverted the behavioral changes to normal. MeHg
      exposure decreases the DNA and RNA content in cerebellum and also caused some
      pathological changes in cerebellum. Pretreatment with BME restored all the
      changes to near normal. These findings suggest that BME has a potent efficacy to
      alleviate MeHg-induced toxicity in rat cerebellum.

PMID- 23872738
TI  - In situ chimerism after double cord blood transplantation.

PMID- 23872739
TI  - Pre-engraftment blood stream infection is a risk factor for acute GVHD grades II
      IV.

PMID- 23872737
TI  - Biologic markers of chronic GVHD.
AB  - Biologic markers of chronic GVHD may provide insight into the pathogenesis of the
      syndrome, identify molecular targets for novel interventions, and facilitate
      advances in clinical management. Despite extensive work performed to date largely
      focused on prediction and diagnosis of the syndrome, little synthesis of findings
      and validation of promising candidate markers in independent populations has been
      performed. Studies suggest that risk for subsequent chronic GVHD development may
      be associated with donor-recipient genetic polymorphism, deficiency in regulatory
      immune cell populations (NK, Treg, DC2), and variation in inflammatory and
      immunoregulatory mediators post-HCT (increased TNFalpha, IL-10 and BAFF, and
      decreased TGFbeta and IL-15). Established chronic GVHD is associated with
      alteration in immune cell populations (increased CD3(+) T cells, Th17, CD4(+) and
      CD8(+) effector memory cells, monocytes, CD86 expression, BAFF/B cell ratio, and
      deficiency of Treg, NK cells, and naive CD8(+) T cells). Inflammatory and
      immunomodulatory factors (TNFalpha, IL-6, IL-1beta, IL-8, sIL-2R, and IL-1Ra,
      BAFF, anti-dsDNA, sIL-2Ralpha, and sCD13) are also perturbed. Little is known
      about biologic markers of chronic GVHD phenotype and severity, response to
      therapy, and prognosis. 

PMID- 23872740
TI  - Outcomes of hematopoietic SCT recipients with rhinovirus infection: a matched,
      case-control study.
AB  - The impact of rhinovirus in hematopoietic SCT (HSCT) recipients is not well
      defined. A retrospective, matched, case-control study of HSCT recipients with
      rhinovirus was conducted between 2009 and 2011. Controls were matched for timing
      relative to transplant, malignancy, and stem cell source. There were 47 cases and
      94 controls. The cases and controls did not differ with respect to age, gender,
      ethnicity, donor source, malignancy, conditioning regimen, immunosuppression,
      antimicrobial prophylaxis or significant comorbidities. There were no differences
      in need for intensive care unit care, 100 day mortality, hospice discharge,
      relapse of disease, GVHD or development of disease or infection due to CMV or
      EBV. Other infectious complications after rhinovirus diagnosis were also equal.
      However, there was an increased number of recurrent hospitalizations from any
      cause among the cases (46.8% vs 24.5%, P=0.007). Recurrent hospitalizations due
      to any infection were also more common in cases (34% vs 14.9%, P=0.015). For
      patients who were diagnosed with rhinovirus pre-transplant (n=13), there was no
      difference in outcome compared with matched controls. HSCT recipients with
      rhinovirus have an increased risk of hospital readmission. However, there was no
      difference in outcome compared with matched controls. Transplantation in patients
      with active rhinovirus infection appears to be safe. 

PMID- 23872741
TI  - Overexpression of PeHA1 enhances hydrogen peroxide signaling in salt-stressed
      Arabidopsis.
AB  - The plant plasma membrane (PM) H(+)-ATPase plays a crucial role in controlling
      K(+)/Na(+) homeostasis under salt stress. Our previous microarray analysis
      indicated that Populus euphratica retained a higher abundance of PM H(+)-ATPase
      transcript versus a salt-sensitive poplar. To clarify the roles of the PM H(+)
      ATPase in salt sensing and adaptation, we isolated the PM H(+)-ATPase gene PeHA1
      from P. euphratica and introduced it into Arabidopsis thaliana. Compared to wild
      type, PeHA1-transgenic Arabidopsis had a greater germination rate, root length,
      and biomass under NaCl stress (50-150 mM). Ectopic expression of PeHA1 remarkably
      enhanced the capacity to control the homeostasis of ions and reactive oxygen
      species in salinized Arabidopsis. Flux data from salinized roots showed that
      transgenic plants exhibited a more pronounced Na(+)/H(+) antiport and less
      reduction of K(+) influx versus wild-type. Enhanced PM ATP hydrolytic activity,
      proton pumping, and Na(+)/H(+) antiport in PeHA1-transgenic plants, were
      consistent to those observed in vivo, i.e., H(+) extrusion, external
      acidification, and Na(+) efflux. Activities of the antioxidant enzymes ascorbate
      peroxidase and catalase were typically higher in transgenic seedlings
      irrespective of salt concentration. In transgenic Arabidopsis roots, H2O2
      production was higher under control conditions and increased more rapidly than
      wild-type when plants were subjected to NaCl treatment. Interestingly, transgenic
      plants were unable to control K(+)/Na(+) homeostasis when salt-induced H2O2
      production was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase.
      These observations suggest that PeHA1 accelerates salt tolerance partially
      through rapid H2O2 production upon salt treatment, which triggers adjustments in
      K(+)/Na(+) homeostasis and antioxidant defense in Arabidopsis.

PMID- 23872742
TI  - Nitric oxide mediates alginate oligosaccharides-induced root development in wheat
      (Triticum aestivum L.).
AB  - Alginate oligosaccharides (AOS), which are marine oligosaccharides, are involved
      in regulating plant root growth, but the promotion mechanism for AOS remains
      unclear. Here, AOS (10-80 mg L(-1)) were found to induce the generation of nitric
      oxide (NO) in the root system of wheat (Triticum aestivum L.), which promoted the
      formation and elongation of wheat roots in a dose-dependent manner. NO inhibitors
      suggested that nitrate reductase (NR), rather than nitric oxide synthase (NOS),
      was essential for AOS-induced root development. Further studies confirmed that
      AOS-induced NO generation in wheat roots by up-regulating the gene expression and
      enzyme activity of NR at the post-transcriptional level. The anatomy and RT-PCR
      results showed that AOS accelerated the division and growth of stele cells,
      leading to an increase in the ratio of stele area to root transverse area. This
      could be inhibited by the NR inhibitor, sodium tungstate, which indicated that NO
      catalyzed by the NR was involved in AOS regulation of root development. Taken
      together, in the early stage of AOS-induced root development, NO generation was a
      novel mechanism by which AOS regulated plant growth. The results also showed that
      this marine resource could be widely used for crop development.

PMID- 23872744
TI  - Band structure and near infrared quantum cutting investigation of GdF3:Yb3+, Ln3+
      (Ln = Ho, Tm, Er, Pr, Tb) nanoparticles.
AB  - A series of GdF3:Yb(3+), Ln(3+) (Ln = Ho, Tm, Er, Pr, Tb) nanoparticles were
      prepared by a simple and green hydrothermal method without any additives, which
      exhibited an ellipse-like shape with a diameter of 63 nm and a length of 101 nm
      on average. To prove the existence (or not) of near infrared quantum cutting for
      various lanthanide ion couples (Yb/Ho; Yb/Tm; Yb/Er; Yb/Pr; Yb/Tb) in one host
      lattice (GdF3), the measured luminescence spectra and decay lifetimes of these
      samples were analysed. Furthermore, the band structures and densities of state of
      GdF3 were also studied with the help of first-principles calculations, and the
      direct band gap of GdF3 was estimated to be 7.443 eV wide. Based on this,
      detailed processes and possible mechanisms of the luminescence phenomena are
      discussed. GdF3:Yb(3+), Ln(3+) nanoparticles may have potential applications in
      modifying the solar spectrum to enhance the efficiency of silicon solar cells. 

PMID- 23872743
TI  - Theoretical studies on the structural and spectroscopic properties of an
      iminocoumarin-based probe and its metal complexation: an implication for a
      fluorescence probe.
AB  - To understand the sensing behaviors of molecular fluorescent probes, an N,N
      di(picolyl)aminoethyl-iminocoumarin probe (L) and its complexation with metal(II)
      ions (ML, M = Mg, Ca, Zn, Cd and Hg) were examined by relativistic density
      functional theory (DFT). Four stable conformational isomers (labeled as g1, g2,
      a1 and a2) for each of them have been optimized, except for CaL having only three
      without the g2 isomer. All of these structures have been confirmed by frequency
      calculations. In the aqueous solution, the a2 isomer of the L probe was
      calculated to be the most stable, while the g1 isomer turns out to be
      energetically favorable upon binding with metal ions. At these isomeric
      geometries, the experimentally obtained absorption was well reproduced by
      calculations of time-dependent DFT (TD-DFT) and a conductor-like polarized
      continuum model (CPCM). A slight red-shifting from L (508 nm) to ML (516-528 nm)
      was found. This is due to the metal affinity that stabilizes the LUMOs of ML
      greater than the HOMOs. Singlet excited-state structures of L and ML (M = Zn, Cd
      and Hg) were fully optimized using the TD-DFT approach, giving more relaxed
      geometries than their respective ground-state ones. Their fluorescent emissions
      in the aqueous solution were calculated to be 543 and 551-560 nm, respectively,
      agreeing with experimental values of 543 nm for L and 558 nm for ZnL. The present
      study also presents theoretical support for a sensing mechanism of photo-induced
      charge transfer of the L probe that was proposed in the previous experiment.

PMID- 23872745
TI  - Racial differences in the incidence and clearance of human papilloma virus (HPV):
      the HPV in men (HIM) study.
AB  - BACKGROUND: This analysis assessed the acquisition (incidence) and persistence
      (clearance) of human papilloma virus (HPV) infection by self-reported race among
      men in The HPV in Men (HIM) Study, a multinational prospective study of the
      natural history of genital HPV infections. METHODS: Self-reported race was
      categorized as White, Black, Asian/Pacific Islander (PI), or multiple and mixed
      race. Genital samples were combined for HPV DNA testing and categorized by any,
      oncogenic, and non-oncogenic HPV infections. RESULTS: Asian/PI race had
      significantly the lowest incidence of any, oncogenic, and non-oncogenic HPV
      infection (P < 0.001). In multivariable analyses, Asian/PI race was associated
      with a lower probability of acquiring any [HR = 0.63; 95% confidence interval
      (CI), 0.42-0.95] and non-oncogenic HPV infection (HR = 0.61; 95% CI, 0.40-0.93)
      when compared to Whites. No significant associations were evident for Asian/PI
      race for clearance. Multiple and mixed race was significantly associated with
      lower probability of acquiring non-oncogenic HPV infection (HR = 0.83; 95% CI,
      0.69-0.99) and borderline significant associations were observed for any HPV (HR
      = 0.91) and oncogenic infections (HR = 0.92). Multiple and mixed race was
      associated with a lower probability of clearing any (HR = 0.92; 95% CI, 0.84
      1.00) and oncogenic HPV infections (HR = 0.85; 95% CI, 0.75-0.95). CONCLUSION:
      Asian/PI race had the lowest incidence of HPV and exhibited a lower probability
      of acquiring new HPV infections. Multiple and mixed race had the second lowest
      incidence of infection and was associated with a lower probability of acquiring
      and clearing an HPV infection. IMPACT: Race-specific differences in HPV infection
      could be due to behavior, innate genetic differences, or circulating intratypic
      HPV variants.

PMID- 23872746
TI  - A mild Lewis acid mediated epoxy-ester to bicyclic ortho ester rearrangement.
AB  - A high yielding rearrangement of epoxy-esters, under Lewis acid conditions, to
      give bicyclic ortho esters is reported. 

PMID- 23872747
TI  - Speckle reduction using an artificial neural network algorithm.
AB  - This paper presents an algorithm for reducing speckle noise from optical
      coherence tomography (OCT) images using an artificial neural network (ANN)
      algorithm. The noise is modeled using Rayleigh distribution with a noise
      parameter, sigma, estimated by the ANN. The input to the ANN is a set of
      intensity and wavelet features computed from the image to be processed, and the
      output is an estimated sigma value. This is then used along with a numerical
      method to solve the inverse Rayleigh function to reduce the noise in the image.
      The algorithm is tested successfully on OCT images of Drosophila larvae. It is
      demonstrated that the signal-to-noise ratio and the contrast-to-noise ratio of
      the processed images are increased by the application of the ANN algorithm in
      comparison with the respective values of the original images. 

PMID- 23872748
TI  - Optical imaging with spectrum aberration correction using a filtering macrolens.
AB  - A filtering macrolens was developed to simultaneously achieve macro-optical
      imaging and correct spectrum aberration. The macrolens was a doublet lens
      comprising a filtering lens and a close-up lens. The shape of the filtering lens
      was designed to eliminate the optical path differences between the light rays in
      the absorbing medium. The close-up lens was designed to decrease the effective
      focal length of an ordinary camera lens to provide high magnification capability
      and collimate the diverging beams through the filtering lens. Experimental
      results demonstrated that the spectrum uniformity of the macro-optical images was
      markedly improved by the filtering macrolens. This innovation may be used in
      finite conjugate optical systems. 

PMID- 23872749
TI  - Asymmetric wavelet reconstruction of particle hologram with an elliptical
      Gaussian beam illumination.
AB  - We propose an asymmetric wavelet method to reconstruct a particle from a hologram
      illuminated by an elliptical, astigmatic Gaussian beam. The particle can be
      reconstructed by a convolution of the asymmetric wavelet and hologram. The
      reconstructed images have the same size and resolution as the recorded hologram;
      therefore, the reconstructed 3D field is convenient for automatic particle
      locating and sizing. The asymmetric wavelet method is validated by both simulated
      holograms of spherical particles and experimental holograms of opaque,
      nonspherical coal particles. 

PMID- 23872750
TI  - High-sensitivity bend angle measurements using optical fiber gratings.
AB  - We present a high-sensitivity and more flexible bend measurement method, which is
      based on the coupling of core mode to the cladding modes at the bending region in
      concatenation with optical fiber grating serving as band reflector. The
      characteristics of a bend sensing arm composed of bending region and optical
      fiber grating is examined for different configurations including single fiber
      Bragg grating (FBG), chirped FBG (CFBG), and double FBGs. The bend loss curves
      for coated, stripped, and etched sections of fiber in the bending region with
      FBG, CFBG, and double FBG are obtained experimentally. The effect of separation
      between bending region and optical fiber grating on loss is measured. The loss
      responses for single FBG and CFBG configurations are compared to discover the
      effectiveness for practical applications. It is demonstrated that the sensitivity
      of the double FBG scheme is twice that of the single FBG and CFBG configurations,
      and hence acts as sensitivity multiplier. The bend loss response for different
      fiber diameters obtained through etching in 40% hydrofluoric acid, is measured in
      double FBG scheme that resulted in a significant increase in the sensitivity, and
      reduction of dead-zone. 

PMID- 23872751
TI  - Output-coupling-dependent laser operation of monoclinic Yb:Ca4LaO(BO3)3 crystal.
AB  - We have studied the laser operation of Yb:LaCOB crystal for what we believe is
      the first time. Adopting a plane-concave cavity, the laser properties were
      measured for the X-cut, Y-cut, and Z-cut crystals. The best output power of 3.2 W
      was obtained with a slope efficiency 69.90% by employing the Y-cut crystal. A
      more efficient operation with slope efficiency of 82.31% was realized for the X
      cut crystal, with the output power of 2.0 W. The laser spectra were collected
      under the absorbed pump power of 3.9 W for X cut and Z cut and 6.7 W for Y cut.
      The emission wavelengths were dependent of the transmittance of output couplers.

PMID- 23872752
TI  - Talbot effect of quasi-periodic grating.
AB  - Theoretic and experimental studies of the Talbot effect of quasi-periodic
      gratings are performed in this paper. The diffractions of periodic and quasi
      periodic square aperture arrays in Fresnel fields are analyzed according to the
      scalar diffraction theory. The expressions of the diffraction intensities of two
      types of quasi-periodic gratings are deduced. Talbot images of the quasi-periodic
      gratings are predicted to appear at multiple certain distances. The quasi
      periodic square aperture arrays are produced with the aid of a liquid crystal
      light modulator, and the self-images of the quasi-periodic gratings are measured
      successfully in the experiment. This study indicates that even a structure in
      short-range disorder may take on the self-imaging effect in a Fresnel field. 

PMID- 23872753
TI  - Estimation of self-absorption effect on aluminum emission in the presence of
      different noble gases: comparison between thin and thick plasma emission.
AB  - Aluminum spectra in the noble gases of helium and argon at initial delay times
      after plasma formation are numerically calculated. Temporal behavior of plasma
      emissions up to 200 ns after laser irradiation is investigated. Plasma parameters
      are computed by coupling the thermal model of laser ablation, hydrodynamic of
      plasma expansion, and Saha-Eggert equations. A spectrum is constructed from the
      superposition of 13 strong lines of aluminum and several strong lines of ambient
      gases. Spectral radiations are superimposed on a continuous emission composed of
      bremsstrahlung and recombination radiation. The self-absorption effect on plasma
      radiation at 1 atm gas pressure is studied. In this paper, a comparison between
      thin and thick aluminum radiation is done. Furthermore, the self-absorption
      coefficient of each strong line at laser energies of 0.5, 0.7, 0.9, and 1.1
      GW/cm(2) is estimated. Results show that at specific laser energy, the self
      absorption effect in argon is more significant than in helium. For most of the
      spectral lines in both noble gases, the self-absorption coefficient will diminish
      with the delay time. As indicated with passing time, the line widths of the self
      absorbed lines will rise. More intense continuous emissions are observed at
      higher wavelengths, and these radiations will be increased with laser energy.

PMID- 23872754
TI  - Degradation of near infrared and shortwave infrared imager performance due to
      atmospheric scattering of diffuse night illumination.
AB  - On moonless nights, airglow is the primary source of natural ground illumination
      in the near infrared and shortwave infrared spectral bands. Therefore, night
      vision imagers operating in these spectral bands view targets that are diffusely
      illuminated. Aerosol scattering of diffuse airglow illumination causes
      atmospheric path radiance and that radiance causes increased imager noise. These
      phenomena and their quantification are described in this paper. 

PMID- 23872755
TI  - Simple and direct measurements of pretilt angles in hybrid-aligned nematic liquid
      crystal cells.
AB  - We have developed a general approach to perform direct measurements of the
      pretilt angles from 0 degrees  to 75 degrees  in hybrid-aligned nematic (HAN)
      liquid-crystal cells whose cell gaps can also be accurately determined with the
      help of known pretilt angles. In this paper, we have used a Zeeman laser system
      to measure the angular-dependence phase retardation of the HAN cells and MATLAB
      mathematical software to carry out theoretical calculations and fit the measured
      data to derive the pretilt angles. In general, pretilt angles adjacent to
      opposite substrates of a HAN cell are different. Our measured pretilt angles of
      the HAN cell were in good agreement with the measured pretilt angles of two
      accompanying homogenous cells whose alignment methods were the same as applied to
      opposite substrates of the HAN cell, respectively. The advantage of direct
      measurement is easily applicable to measure the pretilt angles of aged HAN cells.

PMID- 23872756
TI  - Imaging by a system with a hexagonal pupil.
AB  - We obtain a closed-form analytical expression for the aberration-free point
      spread function (PSF) of a system with a hexagonal pupil. The six-fold symmetric
      PSF consists of a nearly circular bright spot at the center surrounded by a thin
      dark ring and two each nearly hexagonal bright and dark rings, while maintaining
      the six-fold symmetry. Beyond that the PSF breaks into six diffraction arms, each
      of alternating bright and dark strips and normal to a side of the pupil, with
      some dim structure between two consecutive arms. The ensquared power of the PSF
      and the optical transfer function are calculated and compared with the
      corresponding quantities for a system with a circular pupil. The balancing of
      Seidel aberrations is illustrated and their standard deviations with and without
      balancing are discussed. The Strehl ratio of these aberrations is plotted as a
      function of the standard deviation and compared with the approximate expression
      based on the aberration variance. 

PMID- 23872757
TI  - Multi-Fresnel lenses pumping approach for improving high-power Nd:YAG solar laser
      beam quality.
AB  - To significantly improve the present-day high-power solar laser beam quality, a
      three-stage multi-Fresnel lenses approach is proposed for side-pumping either a
      Nd:YAG single-crystal or a core-doped Sm(3+)Nd:YAG ceramic rod. Optimum pumping
      and laser beam parameters are found through ZEMAX and LASCAD numerical analysis.
      The proposed scheme offers a uniform absorption profile along the rod. 167 W
      laser power can be achieved, corresponding to 29.3 W/m(2) collection efficiency.
      High brightness figure of merit of 8.34 W is expected for the core-doped rod
      within a convex-concave resonator, which is 1300 times higher than that of the
      most-recent high-power solar laser.

PMID- 23872758
TI  - Information authentication system using interference of two beams in gyrator
      transform domain.
AB  - A novel information authentication system, i.e., an asymmetric optical
      interference of two beams in the gyrator transform (GT) domain, is proposed. In
      this algorithm, the input color image is divided into R, G, and B channels. The
      complex field of each channel is constructed by the inverse Fourier transform of
      the channel attached with a random phase function. The phase-only mask (POM) and
      amplitude-only mask (AOM) are analytically derived from the complex field. The
      POM and AOM are separately gyrator transformed. The two asymmetric phase keys and
      two encrypted images are obtained by the amplitude truncations and phase
      truncations of the transform images, respectively. Finally, the encoded image is
      produced by the interference of two encrypted images. The two asymmetric keys and
      two angle parameters of the GT are regarded as additional keys for each channel
      to enhance the security level of the cryptosystem. The noniterative
      authentication procedure is devoid of any silhouette problem. The proposed system
      can be implemented digitally or optically, and its architecture is free from
      optical misalignment problems. The theoretical analysis and numerical simulation
      results both validate the proposed technique. 

PMID- 23872759
TI  - Single-step method for fiber-optic probe-based full-range spectral domain optical
      coherence tomography.
AB  - We propose a single-step method appropriated for a fiber-optic probe-based full
      range spectral domain optical coherence tomography (OCT). The fiber-optic probe
      was scanned over a sample with a magnetically driven actuator. In the reference
      arm, a phase shift of pi/2 was applied during two neighbor axial scanning, from
      which the complex spectral interferogram was directly reconstructed. Since the
      complex-conjugate-free OCT image is obtained by doing just one Fourier transform
      on the complex interferogram, obtaining the full-range image is simple in
      algorithm and effective in computation time. Some full-range images of biological
      samples created with the proposed method are presented and the processing time is
      analyzed. 

PMID- 23872760
TI  - Method for the calibration of the spectral irradiance of tungsten filament
      transfer standard sources traceable to synchrotron radiation.
AB  - The spectral irradiance calibration of tungsten strip and spiral filament lamps
      applying synchrotron radiation revealed that the spectral irradiance in the
      wavelength range from 280 to 400 nm can be well approximated by blackbody
      radiation according to Planck's law. Consequently, the spectral irradiance of the
      filament lamp can then be described by an effective irradiance temperature, which
      would be beneficial for practical measurements. Including the emissivity of
      tungsten into the approximation, the model can be expanded to visible and near
      infrared wavelength regions. The effective irradiance temperature dependence of
      the lamp current was investigated and appeared to be close to linear. 

PMID- 23872761
TI  - Evaluation of the estimation accuracy of polarization-based roll angle
      measurement.
AB  - The orientation of remote objects can be easily measured optically and very
      accurately using optical technologies. In this paper, we address the accuracy of
      a roll angle estimation technique that is based on the estimation of the
      polarization of a retroreflected beam and is applied in a long-range measurement
      task. Over long transmission ranges, the optical power decreases significantly
      leading to severe SNR deterioration. As a result, the measurement accuracy
      decreases. In this study, the estimation is carried out using a maximum
      likelihood estimator and its performance is evaluated using the analytical Cramer
      Rao bound. 

PMID- 23872762
TI  - Flexible silver-coated hollow fibers for remote Raman spectroscopic measurements.
AB  - A Raman remote spectroscopy system was established by using flexible hollow
      fibers (HFs) as laser excitation fiber and signal collection fiber. Experimental
      evaluations with various optical fiber combinations were carried out. Experiments
      were conducted by using silver-coated HFs as both remote transmission fiber and
      sample cells for liquid sample detection. Good linearity for concentration
      detection of liquid was obtained with clean background and signal enhancement.
      Theoretical analysis was carried out to optimize the length of the liquid cell.
      Measured data show good agreement with the simulation result. HF has shown
      potentiality in applications for remote and noninvasive Raman detection. 

PMID- 23872763
TI  - Dual-wavelength, continuous-wave Yb:YAG laser for high-resolution photothermal
      common-path interferometry.
AB  - We present a continuous-wave (CW) intracavity frequency-doubled Yb:YAG laser
      providing 1030 and 515 nm output simultaneously. This laser system was designed
      for photothermal common-path interferometry to measure spatially resolved
      profiles of the linear absorption in dielectric media and coatings for visible or
      infrared light as well as of the nonlinear absorption for the combination of
      both. A Z-shape laser cavity was designed, providing a beam waist in which an LBO
      crystal was located for effective second-harmonic generation (SHG). Suitable
      frequency conversion parameters and cavity configurations were discussed to
      achieve the optimal performance of a diode-pumped CW SHG laser. A 12.4 W 1030 nm
      laser and 5.4 W 515 nm laser were developed simultaneously in our experiment. 

PMID- 23872764
TI  - Improved algorithm for elemental analysis by laser-induced breakdown
      spectroscopy.
AB  - We propose a calibration-free algorithm for retrieval of elemental concentrations
      using laser-induced breakdown spectroscopy. This is a simple and improved version
      of other ratio-based algorithms as it needs only one trial parameter to estimate
      all other concentrations. The present algorithm has been used to estimate the
      composition of a brass sample, and the results agree within 1% with electron
      probe microanalyzer measurements. 

PMID- 23872765
TI  - Absolute spectral responsivity measurements of solar cells by a hybrid optical
      technique.
AB  - An irradiance mode, absolute differential spectral response measurement system
      for solar cells is presented. The system is based on combining the monochromator
      based approach of determining the power mode spectral responsivity of cells with
      an LED-based measurement to construct a curve representing the light-overfilled
      absolute spectral response of the entire cell. This curve can be used to predict
      the short-circuit current (I(sc)) of the cell under the AM 1.5 standard reference
      spectrum. The measurement system is SI-traceable via detectors with primary
      calibrations linked to the NIST absolute cryogenic radiometer. An uncertainty
      analysis of the methodology places the relative uncertainty of the calculated
      I(sc) at better than +/-0.8%.

PMID- 23872766
TI  - High etendue UV camera for simultaneous four-color imaging on a single detector.
AB  - We describe a high etendue (0.12 cm(2) sr) camera that, without moving parts,
      simultaneously images four ultraviolet bands centered at 140, 175, 215, and 255
      nm on a single detector into a minimum of ~7500 resolution elements. In addition
      to being an efficient way to make color photometric measurements of a static
      scene, the camera described here enables detection of spatial and temporal
      information that can be used to reveal energy dependent physical phenomena to
      complement the capability of other instruments ranging in complexity from filter
      wheels to integral field spectrographs.

PMID- 23872767
TI  - Counter-countermeasure identification based on multi-element dual band infrared
      detector.
AB  - An infrared (IR) dual band multi-element detector with the abilities of dual band
      IR counter-countermeasure (IRCCM) and spatial filtering is presented for
      effective target detection in a complex tactical environment. The detection
      elements of the detector are specially arranged like a conventional reticle
      pattern. With special design, the ratio of radiation intensity from two IR bands
      can be calculated to distinguish the target from the IR target-flare mixed signal
      and the two detection bands use a common aperture in the seeker. Without a
      reticle in the optical system of the IR seeker, the dual band detector can still
      perform spatial filtering to eliminate background noise effectively. The design
      details of the detector are presented. The performance of the detector's dual
      band IRCCM and spatial filtering are analyzed. Simulation results are presented
      verifying validity of the presented method. 

PMID- 23872768
TI  - Temperature characteristics of the birefringence properties of filled side-hole
      fibers.
AB  - The temperature characteristics of the birefringence of side-hole fibers filled
      with liquids or metal are investigated, aiming at providing a basis for on/off
      temperature sensing. Short pieces of fiber are filled and the change in
      birefringence is registered using measurements in reflective mode of the
      transmitted power through a linear polarizer at 1550 nm. The rapid change in the
      birefringence behavior of the fiber at the temperature of the phase transition of
      the filler substance is shown, and from the measurement data the phase transition
      temperatures can be determined as well as an estimation of the birefringence
      change with temperature. The experimental results are supported by numerical
      simulations.

PMID- 23872769
TI  - Impact of photonic crystal boundary shape on the existence of one-way edge mode.
AB  - The band structure of a two-dimensional photonic crystal (PhC) formed by a
      triangular lattice of air columns in a gyromagnetic material is investigated in
      the case when an external dc magnetic field is applied to it. It is shown that
      large magnetic-field-induced (MFI) bandgap is obtainable by optimizing the
      parameters of the PhC. The interface between a PhC with MFI bandgap and air may
      support unidirectional or bidirectional propagating edge modes, or even no mode,
      closely depending on the boundary shape of the truncated PhC. The transmission
      property of one-way mode sustained by the gyromagnetic PhC boundary is discussed
      through numerical simulation. 

PMID- 23872770
TI  - Modular design of the LED vehicle projector headlamp system.
AB  - A well designed headlamp for a vehicle lighting system is very important as it
      provides drivers with safe and comfortable driving conditions at night or in dark
      places. With the advances of the semiconductor technology, the LED has become the
      fourth generation lighting source in the auto industry. In this study, we will
      propose a LED vehicle projector headlamp system. This headlamp system contains
      several LED headlamp modules, and every module of it includes four components:
      focused LEDs, asymmetric metal-based plates, freeform surfaces, and condenser
      lenses. By optimizing the number of LED headlamp modules, the proposed LED
      vehicle projector headlamp system has only five LED headlamp modules. It not only
      provides the low-beam cutoff without a shield, but also meets the requirements of
      the ECE R112 regulation. Finally, a prototype of the LED vehicle projector
      headlamp system was assembled and fabricated to create the correct light pattern.

PMID- 23872771
TI  - Photocurrent imaging of CdS/Al interfaces based on microscopic analysis.
AB  - We investigate the lateral variations of photocurrent on CdS/Al interfaces, with
      a combination of a semiconductor characterization system and scanning near-field
      optical microscopy, in which the near-field probe is used to locally induce
      photocurrent on the CdS/Al interfaces with high spatial resolution. By analyzing
      the spatially resolved photoresponse, we find that the resolution is worsened in
      the photocurrent images by the lateral diffusion of the photoexcited electrons
      and that the photoelectric properties of the CdS/Al interfaces are strongly
      affected by the bias voltage. Furthermore, in a complementary experiment, we also
      demonstrate that the photocurrent measurements can reveal structures that are not
      present in the case of shear-force data. The analysis demonstrates the band
      structure and microscopic mechanism of CdS/Al heterostructures, which provide an
      effective approach for developing CdS-based photoelectronic devices. 

PMID- 23872772
TI  - Cramer-Rao bounds for intensity interferometry measurements.
AB  - The question of signal-to-noise ratio (SNR) in intensity interferometry has been
      revisited in recent years, as researchers have realized that various innovations
      can offer significant improvements in SNR. These innovations include improved
      signal processing. Two such innovations, the use of positivity and the use of
      knowledge of the general shape of the object, have been proposed. This paper
      investigates the potential gains offered by these two approaches using Cramer-Rao
      lower bounds (CRLBs). The CRLB on the variance of the positivity-constrained
      maximum likelihood (ML) estimate is at best 1/4 of the variance of the
      unconstrained estimator. This is compared to the positivity-constrained ML
      estimator, which delivers a best-case variance reduction of only (1
      1/pi)/2=34.1%. The gains offered by prior knowledge depend on the quality of such
      information, as might be expected from optimal weighting of such data with the
      measured data. Furthermore, biases are induced by the application of constraints,
      and these biases can eliminate some or all of the advantage of lower variances,
      as found when considering the total root-mean-square error. A form of CRLB for
      variance is presented that properly incorporates prior information. 

PMID- 23872773
TI  - Lensless optical data hiding system based on phase encoding algorithm in the
      Fresnel domain.
AB  - A novel and efficient algorithm based on a modified Gerchberg-Saxton algorithm
      (MGSA) in the Fresnel domain is presented, together with mathematical derivation,
      and two pure phase-only masks (POMs) are generated. The algorithm's application
      to data hiding is demonstrated by a simulation procedure, in which a hidden
      image/logo is encoded into phase forms. A hidden image/logo can be extracted by
      the proposed high-performance lensless optical data-hiding system. The
      reconstructed image shows good quality and the errors are close to zero. In
      addition, the robustness of our data-hiding technique is illustrated by
      simulation results. The position coordinates of the POMs as well as the
      wavelength are used as secure keys that can ensure sufficient information
      security and robustness. The main advantages of this proposed watermarking system
      are that it uses fewer iterative processes to produce the masks, and the image
      hiding scheme is straightforward. 

PMID- 23872774
TI  - In-plane switching of vertically aligned negative liquid crystals for high
      transmittance and wide viewing angle.
AB  - We propose a method for in-plane switching of vertically aligned negative liquid
      crystals (LCs) for high transmittance and wide viewing angle. By applying an in
      plane electric field using a double-layered electrode structure, LC molecules can
      be rotated by the vertical as well as the in-plane components of the applied
      field over the entire region so that high transmittance can be achieved. The
      threshold voltage difference can be obtained simply by varying the electrode
      structure, which can reduce the off-axis gamma shift in a multidomain vertical
      alignment LC cell. 

PMID- 23872775
TI  - Color calibration of an RGB camera mounted in front of a microscope with strong
      color distortion.
AB  - This paper aims at showing that performing color calibration of an RGB camera can
      be achieved even in the case where the optical system before the camera
      introduces strong color distortion. In the present case, the optical system is a
      microscope containing a halogen lamp, with a nonuniform irradiance on the viewed
      surface. The calibration method proposed in this work is based on an existing
      method, but it is preceded by a three-step preprocessing of the RGB images aiming
      at extracting relevant color information from the strongly distorted images,
      taking especially into account the nonuniform irradiance map and the perturbing
      texture due to the surface topology of the standard color calibration charts when
      observed at micrometric scale. The proposed color calibration process consists
      first in computing the average color of the color-chart patches viewed under the
      microscope; then computing white balance, gamma correction, and saturation
      enhancement; and finally applying a third-order polynomial regression color
      calibration transform. Despite the nonusual conditions for color calibration,
      fairly good performance is achieved from a 48 patch Lambertian color chart, since
      an average CIE-94 color difference on the color-chart colors lower than 2.5 units
      is obtained. 

PMID- 23872776
TI  - Conceptual design of dedicated road lighting for city park and housing estate.
AB  - We propose dedicated road lighting, which is significantly superior to the
      existing lighting technologies for the city park and housing estate. This
      dedicated lighting employs freeform surfaces to effectively control the optical
      field of the LED source to produce three kinds of illumination modes for the
      curved road, straight road, and the small public square, respectively, perfectly
      matching the road conditions of the city park and housing estate. A mathematical
      model of freeform illumination design is presented to achieve a conceptual design
      of this road lighting, and a numerical technology for solving this design problem
      is introduced for the first time, to our knowledge. An illumination model of this
      conceptual design is constructed. The experimental results of the conceptual
      design tally closely with the target. This dedicated road lighting, integrated
      with energy saving, healthy lighting and artistic beauty, provides a beautiful
      landscape for the city park and the housing estate at night, and will play an
      important role in improving quality of life of the urban inhabitants. 

PMID- 23872777
TI  - Supervised preserving projection for learning scene information based on time-of
      flight imaging sensor.
AB  - In this paper, we propose a new supervised manifold learning approach, supervised
      preserving projection (SPP), for the depth images of a 3D imaging sensor based on
      the time-of-flight (TOF) principle. We present a novel manifold sense to learn
      scene information produced by the TOF camera along with depth images. First, we
      use a local surface patch to approximate the underlying manifold structures
      represented by the scene information. The fundamental idea is that, because TOF
      data have nonstatic noise and distance ambiguity problems, the surface patches
      can more efficiently approximate the local neighborhood structures of the
      underlying manifold than TOF data points, and they are robust to the nonstatic
      noise of TOF data. Second, we propose SPP to preserve the pairwise similarity
      between the local neighboring patches in TOF depth images. Moreover, SPP
      accomplishes the low-dimensional embedding by adding the scene region class label
      information accompanying the training samples and obtains the predictive mapping
      by incorporating the local geometrical properties of the dataset. The proposed
      approach has advantages of both classical linear and nonlinear manifold learning,
      and real-time estimation results of the test samples are obtained by the low
      dimensional embedding and the predictive mapping. Experiments show that our
      approach obtains information effectively from three scenes and is robust to the
      nonstatic noise of 3D imaging sensor data. 

PMID- 23872778
TI  - Mueller matrix holographic method for small particle characterization: theory and
      numerical studies.
AB  - Holographic imaging has proved to be useful for spherical particle
      characterization, including the retrieval of particle size, refractive index, and
      3D location. In this method, the interference pattern of the incident and
      scattered light fields is recorded by a camera and compared with the relevant
      Lorenz-Mie solutions. However, the method is limited to spherical particles, and
      the complete polarized scattering components have not been studied. This work
      extends the Mueller matrix formalism for the scattered light to describe the
      interference light field, and proposes a Mueller matrix holography method,
      through which complete polarization information can be obtained. The mathematical
      formalism of the holographic Mueller matrix is derived, and numerical examples of
      birefringent spheres are provided. The Mueller matrix holography method may
      provide a better opportunity than conventional methods to study anisotropic
      particles. 

PMID- 23872779
TI  - High-birefringence, low-loss porous fiber for single-mode terahertz-wave
      guidance.
AB  - A new kind of polymer porous fiber with elliptical air-holes is designed for
      obtaining high birefringence in the terahertz (THz) frequency range in this
      paper. Using the finite element method, the properties of this kind of fiber are
      simulated in detail including the single-mode propagation condition, the
      birefringence, and the loss. Theoretical results indicate that the single-mode
      THz wave in the frequency range from 0.73 to 1.22 THz can be guided in the fiber;
      the birefringence can be enhanced by rotating the major axis of the elliptical
      air-hole and there exists an optimal rotating angle at 30 degrees . At this
      optimal angle a birefringence as high as 0.0445 can be obtained in a wide
      frequency range. Low-loss THz guidance can be achieved owing to the effective
      reduction of the material absorption in such a porous fiber. This research is
      useful for polarization-maintaining THz-wave guidance. 

PMID- 23872780
TI  - Enhanced multiposition method to suppress the north finding error caused by bias
      drift with fiber optic gyroscopes.
AB  - We present an enhanced multiposition method (EMM) to suppress the north finding
      error caused by bias drift with fiber optic gyroscopes (FOGs). The new proposal
      is a static method to find the true north, and it employs a differential strategy
      and a rotation scheme of increasing step angle. Using the noise model of Allan
      variance, we analyze the north finding errors caused by angle random walk (ARW),
      rate random walk (RRW), and rate ramp (RR) theoretically, where RRW and RR are
      two main noise sources of bias drift, and ARW is the rate white noise.
      Theoretical analysis indicates that, in the traditional multiposition method
      (TMM), as the position number increases, the error caused by ARW decreases while
      that by bias drift increases. Therefore, the suppressions of ARW and bias drift
      are conflicted with each other. The north finding accuracy is limited by bias
      drift. In contrast, in EMM, both errors caused by ARW and bias drift will
      decrease as the position number increases. Experimental results with two specific
      FOGs verify our theoretical analysis. In our experiments, we study the effect of
      position number and step angle on the north finding accuracy. Utilizing the
      proposed EMM, for FOG-1, the north finding error has been reduced by 76.60%, and
      for FOG-2, a 36.33% reduction has been achieved. Our proposal provides a more
      effective and stable way to find true north, and it can also be applied to other
      rate gyroscopes. 

PMID- 23872781
TI  - Reconstruction of laser beam wavefronts based on mode analysis.
AB  - We present the reconstruction of a laser beam wavefront from its mode spectrum
      and investigate in detail the impact of distinct aberrations on the mode
      composition. The measurement principle is presented on a Gaussian beam that is
      intentionally distorted by displaying defined aberrations on a spatial light
      modulator. The comparison of reconstructed and programmed wavefront aberrations
      yields excellent agreement, proving the high measurement fidelity.

PMID- 23872782
TI  - Measurement of the refractive index of microquantity liquid filled in a capillary
      and a capillary wall without destruction.
AB  - A method for measuring the refractive index (RI) of a small volume of liquid and
      a capillary wall is presented in this paper. A transparent capillary filled with
      liquid is used as a cylindrical positive lens; subsequently, the focal length of
      the lens is derived through the base of paraxial approximation, which is recorded
      as a function of the RIs of the liquid and capillary wall. With the RI of a
      capillary wall known, the RI of the liquid can be obtained by measuring the focal
      length of the lens, which is characterized by a microquantity liquid, spatial
      resolution, and easy operation. The RI of the capillary wall can be calculated
      without ruining the capillary if the capillary is filled with a standard liquid
      (RI is known), the deviation of which is less than 0.003 RIU. The factors
      affecting accuracy of the measurement, for instance, the depth of a field (DOF)
      in a reading microscope system and the outer and inner diameters of a capillary
      are analyzed, while illustrating that the effective DOF plays an essential role
      in accurate measurement. 

PMID- 23872783
TI  - A luminescent nanoporous hybrid material based drug delivery system showing
      excellent theranostics potential for cancer.
AB  - A novel hybrid nanoporous material (LNH-1) bearing a tris(propyliminomethyl)
      phloroglucinol fluorescent moiety in the framework has been designed and
      administration of an LNH-1 based drug delivery system containing doxorubicin to
      cancer cells showed inhibition of proliferation, suggesting its future potential
      theranostics application in cancer. 

PMID- 23872784
TI  - The current therapeutic scenario for relapsed mantle cell lymphoma.
AB  - PURPOSE OF REVIEW: Patients with relapsing mantle cell lymphoma (MCL) still
      represent a demanding challenge for the hematooncologist. The dismal prognosis
      and the absence of generally accepted therapeutic standards hamper the clinical
      management of such cases. Moreover, the availability of many targeted approaches,
      in a field so far missing efficient salvage regimens, challenges current
      therapeutic algorithms in these patients. RECENT FINDINGS: Molecular targeted
      drugs provide unprecedented response rates in relapsed and even chemorefractory
      MCL. Many phase II studies demonstrated impressive antilymphoma activity of
      compounds such as bortezomib, lenalidomide and temsirolimus, whereas ongoing
      phase III trials currently assess the 'real world' benefit and the impact on
      survival, both alone and in combination with chemotherapy or monoclonal
      antibodies. Recently, the Bruton's tyrosine kinase inhibitor ibrutinib, targeting
      the B-cell receptor cascade, showed impressive response rates and will be soon
      available in phase III trials. SUMMARY: In the present review we focus on the
      major therapeutic discoveries of the last few years to offer a practical
      algorithm to select the appropriate treatment in patients with relapsed MCL.

PMID- 23872786
TI  - Health tourism on the rise? Evidence from the Balance of Payments Statistics.
AB  - The study assesses the presence and magnitude of global trends in health tourism
      using health-related travel (HRT) spending reported in the International Monetary
      Fund's Balance of Payments Statistics database. Linear regression and quantile
      regression are applied to estimate secular trends of the import and export of HRT
      based on a sample of countries from 2003 to 2009. The results show that from 2003
      to 2009 the import and export of health tourism rose among countries with a high
      volume of such activities (accounting for the upper 40% of the countries), but
      not among those with a low volume. The uneven growth in health tourism has
      generated greater contrast between countries with high and low volumes of health
      tourism activities. However, the growth in the total import of health tourism did
      not outpace the population growth, implying that in general the population's
      tendency to engage in health tourism remained static.

PMID- 23872787
TI  - Solvent-free mechanochemical glycosylation in ball mill.
AB  - Starting from acetobromosugars and an alcohol (alkyl/substituted
      alkyl/akenyl/alkynyl/glyceryl/cyclohexyl/steryl) various O-glycosides have been
      prepared mechanochemically under solvent-free conditions employing a planetary
      ball mill in the presence of metal carbonates (environmentally benign or
      otherwise) as promoters. The method was proven to be mild and efficient and
      applicable on preparative scale for the synthesis of various mono- and
      disaccharide glycosides. 4-Pentenyl glycoside so produced could, in four
      successive reactions in the same pot, be converted in high isolated yields into
      triazole-substituted pentyl glycoside that can find application in the area of
      medicinal chemistry. 

PMID- 23872785
TI  - Insights into the broad cellular effects of nelfinavir and the HIV protease
      inhibitors supporting their role in cancer treatment and prevention.
AB  - PURPOSE OF REVIEW: The development of HIV protease inhibitors more than two
      decades ago heralded a new era in HIV care, changing the infection from
      universally fatal to chronic but controllable. With the widespread use of
      protease inhibitors, there was a reduction in the incidence and mortality of HIV
      associated malignancies. Studies later found these drugs to have promising direct
      antitumor effects. RECENT FINDINGS: Protease inhibitors have a wide range of
      effects on several cellular pathways that are important for tumorigenesis and
      independent of inhibition of the HIV protease, including reducing angiogenesis
      and cell invasion, inhibition of the Akt pathway, induction of autophagy, and
      promotion of apoptosis. Among protease inhibitors, nelfinavir appears to have the
      most potent and broad antineoplastic activities, and also affects replication of
      the oncogenic herpesviruses Kaposi sarcoma-associated herpesvirus and Epstein
      Barr virus. Nelfinavir is being studied for the prevention and treatment of a
      wide range of malignancies in persons with and without HIV infection. SUMMARY:
      Nelfinavir and other protease inhibitors are well tolerated, oral drugs that have
      promising antitumor properties, and may prove to play an important role in the
      prevention and treatment of several cancers. Additional insights into protease
      inhibitors' mechanisms of action may lead to the development of novel cancer
      chemotherapy agents.

PMID- 23872789
TI  - In vitro antiviral activity and underlying molecular mechanisms of dipotassium
      glycyrrhetate against porcine reproductive and respiratory syndrome virus.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) has
      caused large economic losses in the swine industry. Currently, there is no
      effective way to prevent PRRSV infection. In this study, we investigated the
      inhibitory effect of dipotassium glycyrrhetate (DG), a derivative of
      glycyrrhetinic acid, on PRRSV infection ability. METHODS: The cytotoxicity of DG
      was measured by MTT assay, and the effects of DG on PRRSV N gene/protein were
      investigated using real-time PCR, western blot and immunofluorescence assay. In
      addition, the effect of DG on cell apoptosis was analysed by fluorescence
      staining. RESULTS: Our results indicated that DG could effectively inhibit virus
      replication and N gene expression in MARC-145 cells infected with PRRSV. When the
      infected cells received DG, the numbers of apoptotic cells were decreased, and
      the cleaved caspase-3 contents were decreased dramatically. CONCLUSIONS: Our
      study demonstrates that DG could effectively inhibit the PRRS virus via multiple
      pathways including inhibition of virus replication and N gene expression and
      reduction of apoptotic cells. DG can serve as a potential chemical for PRRSV
      prevention and control.

PMID- 23872788
TI  - Synthesis, surface properties, and biocompatibility of 1,2,3-triazole-containing
      alkyl beta-D-xylopyranoside surfactants.
AB  - We are interested in the development of surfactants derived from hemicellulosic
      biomass, as they are potential components in pharmaceuticals, personal care
      products, and other detergents. Such surfactants should exhibit low toxicity in
      mammalian cells. In this study we synthesized a series of alkyl or fluoroalkyl
      beta-xylopyranosides from azides and an alkyne using the copper-catalyzed azide
      alkyne (CuAAC) 'click' reaction in 4 steps from xylose. The purified products
      were evaluated for both their surfactant properties, and for their
      biocompatibility. Unlike other carbohydrate-based surfactants, liquid-crystalline
      behavior was not observed by differential scanning calorimetry. The triazole
      containing beta-xylopyranosides with short (6 carbons) and long (>12 carbons)
      chains exhibited no toxicity at concentrations ranging from 1 to 1000 MUM.
      Triazole-containing beta-xylopyranosides with 8, 10, or 12 carbons caused
      toxicity via apoptosis, with CC50 values ranging from 26-890 MUM. The two longest
      chain compounds did form stable monolayers at the air-water interface over a
      range of temperatures, although a brief transition to an the unstable monolayer
      was observed.

PMID- 23872790
TI  - Patient-reported hereditary breast and ovarian cancer in a primary care practice.
AB  - Identifying women appropriate for cancer genetic counseling referral depends on
      patient-reported family history. Understanding predictors of reporting a high
      risk family is critical in ensuring compliance with current referral guidelines.
      Our objectives were to (1) assess prevalence of candidates for BRCA1 and BRCA2
      counseling referral in a primary care setting, (2) explore associations with high
      risk status and various patient (e.g., race) and family structure (e.g., number
      of relatives) characteristics, and (3) determine whether high-risk patients had
      genetic counseling and/or testing. Survey and pedigree data were collected
      between 2010 and 2012 for 486 Women's Health Clinic patients. Analyses in 2013
      investigated perceived cancer risk and worry, family structure, and receipt of
      genetic counseling. We explored whether these were associated with meeting USPSTF
      guidelines for genetic counseling referral. Twenty-two (4.5 %) women met the
      criteria for BRCA referral. Only one of these women had previous genetic
      counseling, and one reported prior genetic testing. Older women were more likely
      to meet BRCA referral criteria (P < 0.001). Although perceived risk was higher
      among high-risk women, 27 % of high-risk women felt their breast cancer risk was
      "low", and 32 % felt their risk was lower than average. About one in 22 women in
      primary care may require genetics services for hereditary breast and ovarian
      cancer, but alarmingly, few actually receive these services. Also, a significant
      proportion do not perceive that they are at increased risk. Educational
      interventions may be needed for both providers and patients to increase awareness
      of familial risk and appropriate genetic counseling services. 

PMID- 23872791
TI  - Imaging bacterial protein expression using genetically encoded RNA sensors.
AB  - The difficulties in imaging the dynamics of protein expression in live bacterial
      cells can be overcome by using fluorescent sensors based on Spinach, an RNA that
      activates the fluorescence of a small-molecule fluorophore. These RNAs
      selectively bind target proteins and exhibit fluorescence increases that enable
      protein expression to be imaged in living Escherichia coli. These sensors are key
      components of a generalizable strategy to image protein expression in a single
      bacterium in real time. 

PMID- 23872793
TI  - Cost of delivering child health care through community level health workers: how
      much extra does IMNCI program cost?
AB  - BACKGROUND AND METHODS: In the setting of a cluster randomized study to assess
      impact of the Integrated Management of Neonatal and Childhood Illnesses (IMNCI)
      program in the district of Faridabad in India, we randomly selected auxiliary
      nurse midwives (ANM), anganwadi workers (AWW) and accredited social health
      activists (ASHA) from intervention and control areas to collect cost data using
      an economic perspective. Bootstrap method was used to estimate 95% confidence
      interval. RESULTS: The annual per-child cost of providing health services through
      an ANM, AWW and ASHA is INR 348 (USD 7.7), INR 588 (USD 13.1) and INR 87 (USD
      1.9), respectively. The annual per-child incremental cost of delivering IMNCI is
      INR 124.8 (USD 2.77), INR 26 (USD 0.6) and INR 31 (USD 0.7) at the ANM, AWW and
      ASHA level, respectively. CONCLUSION: Implementation of IMNCI imposes additional
      costs to the health system. A comprehensive economic evaluation of the IMNCI is
      imperative to estimate the net cost implications in India.

PMID- 23872792
TI  - Hoxb8 regulates expression of microRNAs to control cell death and
      differentiation.
AB  - Hoxb8 overexpression immortalises haematopoietic progenitor cells in a growth
      factor-dependant manner and co-operates with interleukin-3 (IL-3) to cause acute
      myeloid leukaemia. To further understand how Hoxb8 contributes to myeloid cell
      immortalisation, we generated IL-3-dependant myeloid cells expressing Hoxb8 under
      the control of an inducible promoter. Downregulation of Hoxb8, in the presence of
      IL-3, caused cell-cycle arrest and apoptosis in the majority of cells. Apoptosis
      was dependant on Bax and Bak and, in part, on Bim, which was repressed by Hoxb8.
      Deletion of the miR-17~92 seed sequences in the Bim 3'UTR abolished Hoxb8
      dependant regulation of Bim reporter constructs. Expression of all six miRNAs
      from this cluster were elevated when Hoxb8 was overexpressed. The miR-17~92
      cluster was required for repression of Bim in Hoxb8-immortalised cells and
      deletion of the miR-17~92 cluster substantially inhibited Hoxb8, but not Hoxa9,
      mediated survival and proliferation. Hoxb8 appears to promote miR-17~92
      expression through c-Myc, a known transcriptional regulator of the miR-17~92
      cluster. We have uncovered a previously unrecognised link between Hoxb8
      expression and microRNAs that provides a new insight into the oncogenic functions
      of Hoxb8. 

PMID- 23872794
TI  - ACR Appropriateness Criteria(r) management of locoregionally advanced squamous
      cell carcinoma of the vulva.
AB  - OBJECTIVES: Locoregionally advanced vulvar cancer (LRAVC) is a rare disease that
      presents many challenging medical decisions. An expert panel was convened to
      reach consensus on the most appropriate pretreatment assessment and therapeutic
      interventions in LRAVC patients. METHODS: The American College of Radiology
      Appropriateness Criteria are evidenced-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 journal and the application of a well
      established consensus methodology (modified Delphi) to rate 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 formulate
      recommendations. RESULTS: Three clinical variants were developed to address
      common scenarios in the management of LRAVC. Group members reached consensus on
      the appropriateness of specific evaluation and treatment approaches, with
      numerical ratings and descriptive commentary. CONCLUSIONS: In combining available
      medical literature and expert opinion, this manuscript may serve as an aid for
      other practitioners in the appropriate management of patients with LRAVC.

PMID- 23872795
TI  - Immunomodulatory activity of enzymatically synthesized glycogen and its digested
      metabolite in a co-culture system consisting of differentiated Caco-2 cells and
      RAW264.7 macrophages.
AB  - Previously, we developed enzymatically synthesized glycogen (ESG) from starch,
      and showed its immunomodulatory and dietary fiber-like activities. In this study,
      we investigated the metabolism of ESG and its immunomodulatory activity using
      differentiated Caco-2 cells as a model of the intestinal barrier. In a co-culture
      system consisting of differentiated Caco-2 cells and RAW264.7 macrophages, mRNA
      expression of IL-6, IL-8, IL-1beta and BAFF cytokines was up-regulated in Caco-2
      cells and IL-8 production in basolateral medium was induced after 24 h apical
      treatment with 5 mg ml(-1) of ESG. The mRNA level of iNOS was also up-regulated
      in RAW264.7 macrophages. After characterization of the binding of anti-glycogen
      monoclonal antibodies (IV58B6 and ESG1A9) to ESG and its digested metabolite
      resistant glycogen (RG), an enzyme-linked immunosorbent assay (ELISA) system was
      developed to quantify ESG and RG. Using this system, we investigated the
      metabolism of ESG in differentiated Caco-2 cells. When ESG (7000 kDa, 5 mg ml(
      1)) was added to the apical side of Caco-2 monolayers, ESG disappeared and RG
      (about 3000 kDa, 3.5 mg ml(-1)) appeared in the apical solution during a 24 h
      incubation. Neither ESG nor RG was detected in the basolateral solution. In
      addition, both ESG and RG were bound to TLR2 in Caco-2 cells. In conclusion, we
      suggest that ESG is metabolized to a RG-like structure in the intestine, and this
      metabolite activates the immune system via stimulation of the intestinal
      epithelium, although neither ESG nor its metabolite could permeate the intestinal
      cells under our experimental conditions. These results provide evidence for the
      beneficial function of ESG as a food ingredient. 

PMID- 23872796
TI  - MR perfusion index as a quantitative method of evaluating epiphyseal perfusion in
      Legg-Calve-Perthes disease and correlation with short-term radiographic outcome:
      a preliminary study.
AB  - BACKGROUND: Current radiographic prognosticators of the outcome of Perthes
      disease can only be applied after femoral head deformity has occurred.
      Quantification of femoral head perfusion using the gadolinium-enhanced
      subtraction magnetic resonance imaging (MRI) technique may serve as an early
      prognosticator of outcome. The purposes of this study were 2-fold: (1) to develop
      a reliable method to quantify femoral head perfusion using this MRI technique;
      and (2) to determine whether the perfusion at early stages of Perthes disease
      correlates with radiographic deformity after a 2-year follow-up. METHODS: A total
      of 20 patients meeting the following inclusion criteria were studied: radiographs
      and MRI obtained of femoral heads predeformity, age between 5 and 13 years, and
      unilateral disease. MR perfusion index, a measure of perfusion in the epiphysis,
      was obtained using digital image analysis of subtraction gadolinium-enhanced MRI.
      Intraobserver and interobserver agreement of this index was assessed by 2
      independent observers. MR perfusion index was correlated with a radiographic
      deformity index (a measure of femoral head deformity) obtained after a minimum of
      2 years. RESULTS: The intraobserver agreement assessed by the intraclass
      correlation coefficient was 0.96 for observer 1 and 0.97 for observer 2. The
      interobserver agreement of the MR perfusion index was 0.90 for trials 1 and 2. MR
      perfusion index in the early stages of Perthes disease was highly variable,
      ranging from 0 to 0.70. After a minimum of 2 years following MRI acquisition,
      radiographs were obtained and evaluated using the deformity index, a continuous
      measure of femoral head deformity, by 2 blinded observers. Deformity index at 2
      year follow-up showed moderate correlation with predeformity MR perfusion index
      (r=-0.56, P=0.01, R=0.31). In those patients who were treated nonoperatively, the
      correlation was stronger (r=-0.79, P=0.006, R=0.63). CONCLUSIONS: MR perfusion
      index obtained from gadolinium-enhanced subtraction MR images showed a high
      interobserver agreement. MR perfusion index is highly variable at early stages of
      Perthes disease, and a lower MR perfusion index correlated with greater
      radiographic deformity at the 2-year follow-up. This pilot study shows the
      promise of predeformity MR perfusion index as a possible early prognosticator of
      outcome in Perthes disease. LEVELS OF EVIDENCE: Prognostic level II.

PMID- 23872797
TI  - Anterior cruciate ligament reconstruction in children with a quadrupled
      semitendinosus graft: preliminary results with minimum 2 years of follow-up.
AB  - BACKGROUND: The management of anterior cruciate ligament (ACL) tears in growing
      patients must balance activity modification with the risk of secondary (meniscal
      and cartilaginous) lesions, and surgical intervention, which could adversely
      affect skeletal growth. Many ACL reconstruction techniques have been developed or
      modified to decrease the risk of growth disturbance. We have not found any
      description of ACL reconstruction using a single hamstring, short graft implanted
      into intraepiphyseal, retroreamed sockets. Our hypothesis was that the technique
      that we used restored the knee stability and did not cause any growth
      disturbances. METHODS: We retrospectively studied 28 patients (20 boys, 8 girls)
      who presented with a unilateral ACL tear and open growth plates. We performed
      short graft ligament reconstruction with the semitendinosus folded into 4 strands
      around 2 polyethylene terephthalate tapes. The graft was implanted into sockets
      that were retroreamed in the femoral and tibial epiphysis and the tapes were
      fixed remotely by interference screws. After a minimum period of 2 years, we
      evaluated the comparative knee laxity, the radiographic limb morphology, the
      appearance of secondary lesions, and the functional outcomes using the Lysholm
      and Tegner scores. Comparative analyses were performed using the Student t test
      with subgroups depending on the type of fixation used. RESULTS: The mean age of
      the patients was 13 years (range, 9 to 15 y). The mean follow-up was 2.8 years
      (range, 2 to 5 y). The mean difference in laxity at 134 N was 0.3 mm, as
      determined using a GNRB arthrometer. No patients reported meniscal symptoms or
      degenerative changes. We found no angular deformity or leg length inequality. Two
      patients suffered a recurrent ACL tear. CONCLUSIONS: The preliminary results from
      this series are consistent with prior studies demonstrating that intraepiphyseal
      ACL reconstruction is a safe reliable alternative for the pediatric population.
      STUDY DESIGN: Case series; level of evidence 4.

PMID- 23872798
TI  - Meta-analysis of function after secondary shoulder surgery in neonatal brachial
      plexus palsy.
AB  - BACKGROUND: Shoulder internal rotation contracture, active abduction, and
      external rotation deficits are common secondary problems in neonatal brachial
      plexus palsy (NBPP). Soft tissue shoulder operations are often utilized for
      treatment. The objective was to conduct a meta-analysis and systematic review
      analyzing the clinical outcomes of NBPP treated with a secondary soft-tissue
      shoulder operation. METHODS: A literature search identified studies of NBPP
      treated with a soft-tissue shoulder operation. A meta-analysis evaluated success
      rates for the aggregate Mallet score (>= 4 point increase), global abduction
      score (>= 1 point increase), and external rotation score (>= 1 point increase)
      using the Mallet scale. Subgroup analysis was performed to assess these success
      rates when the author chose arthroscopic release technique versus open release
      technique with or without tendon transfer. RESULTS: Data from 17 studies and 405
      patients were pooled for meta-analysis. The success rate for the global abduction
      score was significantly higher for the open technique (67.4%) relative to the
      arthroscopic technique (27.7%, P<0.0001). The success rates for the global
      abduction score were significantly different among sexes (P=0.01). The success
      rate for external rotation was not significantly different between the open
      (71.4%) and arthroscopic techniques (74.1%, P=0.86). No other variable was found
      to have significant impact on the external rotation outcomes. The success rate
      for the aggregate Mallet score was 57.9% for the open technique, a nonsignificant
      increase relative to the arthroscopic technique (53.5%, P=0.63). Data suggest a
      correlation between increasing age at the time of surgery and a decreasing
      likelihood of success with regards to aggregate Mallet with an odds ratio of 0.98
      (P=0.04). CONCLUSIONS: Overall, the secondary soft-tissue shoulder operation is
      an effective treatment for improving shoulder function in NBPP in appropriately
      selected patients. The open technique had significantly higher success rates in
      improving global abduction. There were no significant differences in the success
      rates for improvement in the external rotation or aggregate Mallet score among
      these surgical techniques.

PMID- 23872799
TI  - Prevention of postoperative osteopenia using IV pamidronate: a pilot study.
AB  - BACKGROUND: Postoperative bone mineral density (BMD) loss, especially after cast
      immobilization and/or non-weight-bearing, is a well-known phenomenon in children
      that can cause fracture. Children with marginal bone density are at greatest
      risk. This prospective randomized control trial compared the effect of single
      dose intravenous (IV) pamidronate versus placebo to prevent postoperative BMD
      loss. METHODS: Children between the ages of 4 and 18 were included in the study;
      inclusion criteria included a predisposition to low bone density and hip or lower
      extremity surgery that would require cast immobilization or non-weight-bearing
      for at least 4 weeks. Dual-energy x-ray absorptiometry (DXA) scans of the lumbar
      spine and bilateral distal femora were performed preoperatively and at least 4
      weeks postoperatively. Subjects were randomized to receive either a single, low
      dose of IV pamidronate (1 mg/kg) or placebo, given during the immediate
      postoperative period. Changes in the BMD were compared using the Mann-Whitney
      test for significance in the lumbar spine. A multivariate general linear model
      was used to compare the effect of surgery, DXA region, and treatment on BMD.
      RESULTS: A total of 24 subjects were included in the study, and 20 completed the
      protocol. Pamidronate-treated subjects showed a statistically significant
      difference with a median gain in BMD of 0.029 gm/cm in the lumbar spine compared
      with the control group, which showed a median loss of 0.025 gm/cm. Treatment did
      not have a statistically significant effect on BMD loss in the distal femur but
      trended toward decreased BMD loss (treatment=0.0331 gm/cm, control=0.0416 gm/cm).
      There were no complications or adverse reactions. CONCLUSIONS: This small pilot
      study shows that single-dose postoperative pamidronate mitigated postoperative
      BMD loss in at-risk children, which may in turn decrease postoperative fracture
      risk. Further investigation into the use of IV pamidronate in postoperative
      patients is warranted. LEVEL OF EVIDENCE: Level 1 double-blinded randomized
      control trial.

PMID- 23872800
TI  - Dual 8-plate technique is not as effective as ablation for epiphysiodesis about
      the knee.
AB  - BACKGROUND: Lower extremity length inequality can be problematic in children and
      is often addressed surgically. Several techniques have traditionally been
      utilized for epiphysiodesis, the goal being physeal ablation. Recently, 8-plates,
      initially developed for hemiepiphysiodesis, have been extended to epiphysiodesis
      by placing the plates on both medial and lateral sides of the physis. No prior
      studies have compared 8-plates with physeal ablation techniques. METHODS: Between
      January 2003 and August 2009, 27 patients underwent epiphysiodesis surgery using
      either physeal ablation or 8-plate technique. Sixteen patients had physeal
      ablation and 11 had dual 8-plates. A retrospective chart review sought
      demographic data, outcomes, and complications. Radiographs were reviewed to
      measure pretreatment and posttreatment limb lengths. RESULTS: The median
      improvement in limb length discrepancy was 15.5 mm in the physeal ablation group
      and 4 mm in the 8-plate group (P<0.001). This difference was maintained following
      linear regression factoring out the effect of time (10.78 mm for ablation vs.
      5.62 mm for 8-plates; P=0.016). There was no statistically significant difference
      in complication rate between the groups (P=0.112). CONCLUSIONS: Our study
      demonstrated physeal ablation to be a significantly superior treatment compared
      with dual 8-plates for epiphysiodesis. Despite theoretical advantages of 8-plates
      to perform epiphysiodesis about the knee, this study does not recommend the use
      of medial and lateral 8-plates to effect epiphysiodesis. LEVEL OF EVIDENCE:
      Therapeutic III.

PMID- 23872801
TI  - Psychosocial effects of repetitive surgeries in children with early-onset
      scoliosis: are we putting them at risk?
AB  - BACKGROUND: The use of growing instrumentation in children with early-onset
      scoliosis (EOS) has created interest in determining if these repetitive
      procedures are prompting the development of lasting psychosocial problems. Given
      the increasing role of this treatment modality in the management of EOS, this
      study aimed to assess the psychological status of this patient population and to
      determine factors associated with worse scores in various psychosocial domains.
      METHODS: A cross-sectional assessment of 34 EOS patients was performed utilizing
      2 well-established, caregiver-completed psychiatric instruments: the Child
      Behavior Checklist (CBCL) and the Strength and Difficulties Questionnaire. Scores
      were calculated for 15 CBCL and 6 Strength and Difficulties Questionnaire domains
      and subdomains and grouped as "Normal" or "Abnormal" according to published
      normative values. The prevalence of abnormal scores was within each instrument
      subdomain and was compared with the national norms. Domain scores were also
      correlated with age at first scoliosis surgery, total number of operative
      procedures, and total number of growing instrumentation surgeries. RESULTS: A
      higher prevalence of Abnormal scores were found in multiple psychosocial domains
      in our cohort as compared with national normative data. Children with Abnormal
      CBCL "Total Problems" domain scores were younger at the time of first scoliosis
      surgery (2.50 vs. 5.52 y). Normal and Abnormal scoring groups showed significant
      differences in the number of (1) total surgeries; (2) total scoliosis surgeries;
      and (3) growing instrumentation surgeries in multiple domains on both
      instruments. Aggression, Rule-breaking, and Conduct were positively correlated
      with total number of surgeries. CONCLUSIONS: Our findings showed a higher
      prevalence of Abnormal psychosocial scores in multiple domains in multioperated
      EOS patients as compared with national norms. Our findings suggest that EOS
      patients with abnormal psychosocial scores were younger at the time of their
      initial scoliosis surgery. The number of repetitive surgeries also correlated
      positively with 3 behavioral problem scores. Although healthier scores were seen
      in 1 positive behavioral domain in more operated children suggesting the
      potential for "posttraumatic growth," the other findings of this study are
      concerning given the increasing use of this treatment modality and indicate a
      need for ongoing screening and mental health care in this high-risk population.
      LEVEL OF EVIDENCE: Level III--case-control.

PMID- 23872802
TI  - Femoral lengthening over a pediatric femoral nail: results and complications.
AB  - BACKGROUND: Limb lengthening by callotasis as described by Ilizarov has become
      the standard method of lower extremity lengthening. Lengthening over an
      intramedullary nail to allow early removal of the external fixator has also
      become common in adults but few studies have addressed the efficacy in children.
      METHODS: A retrospective review of 37 consecutive children who had undergone
      femoral lengthening with external fixator over an intramedullary nail was
      performed. Charts were reviewed for demographics, surgical details, and
      complications. Radiographs were examined to determine magnitude of lengthening
      and to calculate lengthening index. RESULTS: The average age of the 37 patients
      was 11.6 years (range, 8.1 to 17.0). The amount of lengthening averaged 7.0 cm
      (range, 3.0 to 11.4 cm), which represented a mean 20.4% increase in length. The
      mean time in the fixator was 81 days. The lengthening index was 1.21 days/mm.
      Thirteen patients developed major complications (37.8%) including 4 limbs that
      failed to lengthen initially, 3 fractures (1 before fixator removal and 3 after
      fixator removal), 2 nail failures, 4 deep infections, and 2 joint subluxations
      requiring operative care. The 3 fractures after fixator removal were treated with
      exchange nailing as were the 2 intramedullary nail failures. Four patients
      (10.8%) developed deep infections requiring irrigation, debridement, and IV
      antibiotics. One patient developed a late hip subluxation, which was treated with
      a shelf osteotomy but resulted in pain and limitation of motion. One patient
      developed knee subluxation during lengthening requiring operative intervention.
      The technique was successful in obtaining a good result with a functional
      lengthened femur without unresolved problems in 94% of the patients despite a
      significant rate of major complications, particularly in those with a congenital
      etiology. Only 2 of the 37 patients ultimately had results that were ultimately
      compromised by complications. CONCLUSIONS: Femoral lengthening over an
      intramedullary nail with the aid of an external fixator has shown to be an
      effective method for correcting limb length discrepancy. The technique has a high
      complication rate similar to other methods of lengthening. LEVEL OF EVIDENCE:
      Level IV-Case Series.

PMID- 23872803
TI  - Does medial patellofemoral ligament reconstruction decrease patellar height? A
      preliminary report.
AB  - BACKGROUND: The purpose of this study was to evaluate the hypothesis that medial
      patellofemoral ligament (MPFL) reconstruction for patellar instability decreases
      patellar height. METHODS: Preoperative and postoperative lateral knee radiographs
      of 38 adolescents who underwent MPFL reconstruction between 2005 and 2011 were
      reviewed. The Insall-Salvati index, Blackburne-Peel index, Caton-Deschamps index,
      and plateau-patella angle were measured on all radiographs to identify
      differences in patellar height. These patellar height indices were also measured
      on lateral knee radiographs of 25 adolescents (control group) who were treated
      conservatively for osteochondritis dissecans of the knee. The 2 groups were
      compared to account for patellar height changes secondary to growth and
      ossification. Intrarater reliability was measured for all patellar height indices
      at 1-month interval. RESULTS: Preoperatively, patients who underwent MPFL
      reconstruction had significantly greater patellar height on all indices compared
      with the control group before and after controlling for age and sex. The patients
      who underwent MPFL reconstruction showed a significantly greater decrease in
      patellar height on the Blackburne-Peel or Caton-Deschamps indices over time
      compared with the control group such that postoperatively there was no difference
      between groups in these patellar height indices. Furthermore, the change in
      patellar height indices after MPFL reconstruction did not differ between patients
      with less than or more than 1-year follow-up. All indices demonstrated good to
      excellent intrarater reliability. CONCLUSIONS: The present study showed a
      decrease in patellar height in the postoperative period in patients after MPFL
      reconstruction for patellar instability. Further investigation is necessary to
      determine the long-term effects of MPFL reconstruction on patellar height. LEVEL
      OF EVIDENCE: Level III--therapeutic, case series.

PMID- 23872804
TI  - Do children with Blount disease have lower body mass index after lower limb
      realignment?
AB  - BACKGROUND: Children with Blount disease are typically obese. The goal of our
      study was to assess whether children with Blount disease had lower body mass
      index (BMI) after surgical correction of their lower limb deformity. METHODS: A
      surgical data base was used to identify children with Blount disease. Demographic
      information including age of disease onset, ethnicity, health insurance status,
      and laterality was noted. Preoperative and most recent BMI values were
      documented. Using full-length standing radiographs, the mechanical axis deviation
      (MAD) and leg length discrepancy (LLD) were measured preoperatively and at latest
      follow-up. The relationship of the change in BMI with various demographic and
      radiologic parameters was evaluated. RESULTS: Fifty-one children (32 males, 19
      females) with Blount disease (23 early onset, 28 late onset) affecting 70 lower
      extremities (32 unilateral and 19 bilateral) underwent a variety of surgical
      procedures. All 47 children who underwent gradual correction with external
      fixation also underwent nutritional counseling while receiving inpatient
      rehabilitation. At an average follow-up of 48 months, MAD improved from 80.5 mm
      medial to 16.1 mm medial (P<0.0001) and LLD improved from 19.6 to 10.9 mm
      (P=0.0002). During the same time period, the BMI increased from 35 (95%
      confidence interval, 32-37) to 38 (95% confidence interval, 35-41; P=0.0006).
      Compared with their preoperative BMI, 76% of the children had an increase in
      their BMI at the latest follow-up. There was no association of the change in the
      patient's BMI with their age of disease onset, sex, ethnicity, health insurance
      status, final MAD, or LLD. There was a tendency for the patient's BMI to increase
      with longer follow-up (P=0.002). Using multivariate analysis, only the length of
      follow-up was associated with an increase in BMI (P=0.026). CONCLUSIONS: Despite
      improvement in limb alignment and LLD after surgery, the BMI of the majority of
      children with Blount disease increased over time. Other strategies for addressing
      obesity amongst these children are warranted. LEVEL OF EVIDENCE: Level IV--case
      series.

PMID- 23872805
TI  - Complications and outcomes of diaphyseal forearm fracture intramedullary nailing:
      a comparison of pediatric and adolescent age groups.
AB  - BACKGROUND: Flexible intramedullary nailing (IMN) has become a popular technique
      for the management of unstable or open forearm fractures. Recent publications
      have suggested an increased incidence of delayed union and poor outcomes in older
      children and adolescents. The objective of this study was to review forearm
      fractures treated with IMN, comparing the rate of complications and outcomes
      between the 2 age groups. Our hypothesis was that IMN is an effective technique
      with a similar rate of complications in both age groups. METHODS: An
      Institutional Review Board-approved retrospective review was conducted of
      pediatric forearm fractures treated from 1998 to 2008 at a single institution.
      Over the study time period, 4161 pediatric forearm fractures were managed
      nonoperatively (92%) and 353 were treated operatively with plate, cross-pin, or
      intramedullary fixation (8%). Patients with inadequate follow-up, cross-pin, or
      plate fixation were excluded. Medical records were reviewed for indications and
      complications. Complications were graded with a modification of the Clavien-Dindo
      classification. Outcomes were judged by a new grading system. RESULTS: A total of
      205 forearm fractures treated with IMN in 203 patients were identified. The mean
      age was 9.7 years (range, 1.7 to 16.2 y) and mean follow-up was 42 weeks.
      Operative indications were failure of closed treatment in 165 (80%) and open
      fracture in 40 (20%). Mean time from injury to IMN was 5.9 days (range, 0 to 25
      d). Single bone IMN was performed in 40 of 185 both bone fractures (26%); there
      were 20 single-bone forearm fractures treated with IMN. Open reduction was
      required in 61/165 (37%) of closed fractures. Asymptomatic delayed union (grade 1
      complication) was observed in 9 fractures (4%). More severe complications were
      noted in 17% (grade 2 to 4 complications). Postoperative compartment syndrome
      occurred in 3 isolated forearm fractures with a significant younger mean age (6.0
      vs. 10 y, P=0.031). Overall, complications were significantly more frequent in
      children older than 10 years of age (25/101) as compared with younger children
      (13/104, P=0.031). In particular, delayed union was more common in children over
      the age of 10 years (9/101 vs. 1/104, OR=9.99, P=0.009). Outcomes were good or
      excellent in 91% of fractures. There was no statistical association of patient
      age with a fair or poor outcome. CONCLUSIONS: IMN is an effective technique for
      pediatric forearm fractures with good to excellent outcomes in 91%. Complications
      are not infrequent with this technique, with complications of grade 2 to 4
      severity in 17%. There was a 2-fold increase in the rate of complications in
      children over the age of 10 years. Compartment syndrome was more common in
      younger children. Patients and families should be counseled about the risks
      preoperatively.

PMID- 23872806
TI  - Independent analysis of a clinical predictive algorithm to identify methicillin
      resistant Staphylococcus aureus osteomyelitis in children.
AB  - BACKGROUND: The number of serious, life-threatening musculoskeletal infections in
      children due to methicillin-resistant Staphylococcus aureus (MRSA) infections is
      increasing. The early identification of the bacteria causing osteomyelitis is
      critical to determine the appropriate antibiotic treatment. A recent study
      proposed a clinical algorithm to predict which infections were caused by MRSA by
      stratifying basic clinical values at the time of admission for children with
      osteomyelitis. The purpose of this study is to apply that predictive algorithm on
      an independent patient population to determine its wider applicability. METHODS:
      This was a retrospective chart review at a tertiary care children's hospital. All
      children who were treated for a culture-positive osteomyelitis were identified
      over a 3-year period. The previously reported predictors, determined by
      multivariate regression analysis, of MRSA infection (temperature >38 degrees C,
      hematocrit <34%, white blood cell count >12,000/uL, and C-reactive protein >13
      mg/L) were determined for each patient. The number of positive predictors was
      then correlated with the percentage of cases that were MRSA positive. RESULTS: A
      total of 58 patients with culture-positive osteomyelitis were identified from
      2008 to 2010. Sixteen of the infections were caused by MRSA (overall 26%). The
      percentage of patients with MRSA osteomyelitis according to the number of risk
      factors were as follows: all 4 risk factors, 50% (1 out of 2 patients); 3 risk
      factors, 42% (5 out of 12 patients); 2 risk factors, 21% (4 out of 19 patients);
      1 risk factor, 50% (6 out of 12 patients); and 0 risk factor, 0% (0 out of 13
      patients). CONCLUSIONS: The previously reported clinical predictive algorithm had
      a relatively poor diagnostic performance in this independent patient population.
      Specifically, the percentages of MRSA were the same for 1 risk factor compared
      with 4 (50%). Differences in bacteria strain, host responses, and a variety of
      other confounding variables could be responsible for these differences. Specific
      genetic markers may be the best early test to identify MRSA infections in the
      future. LEVEL OF EVIDENCE: Level III-case-control series.

PMID- 23872807
TI  - The Boyd amputation in children: indications and outcomes.
AB  - BACKGROUND: The level of amputation in the pediatric population requires
      appropriate planning to provide an optimal residual limb for prosthetic fitting
      and must include long-term strategies to accommodate future growth of the
      extremity. METHODS: A retrospective review over a 15-year period was performed of
      all Boyd procedures (calcaneotibial fusion) in the pediatric limb deficiency
      population at a single institution. A chart review and radiographic analysis was
      performed to identify the indications, surgical outcomes, complications, need for
      additional surgical intervention, and nature of the postoperative prosthetic
      management. Optimal positioning of the calcaneotibial fusion and the growth
      dependent changes in the morphology of the fusion site were determined by
      radiographic analysis. RESULTS: A total of 109 children (117 limbs) were
      identified for inclusion in the study. The average age at the time of the Boyd
      procedure was 2.8 years. The most common indication for the Boyd procedure was a
      diagnosis of postaxial limb bud deficiency, which accounted for 66% of cases.
      Concomitant procedures were performed in 24% of cases and included proximal
      tibial epiphyseodesis, tibial osteotomy, or knee fusion in the majority of cases.
      Additional procedures were required in 33% of cases either for treatment of
      complication (9%) or optimization of the residual limb (24%). For the entire
      cohort, the complication rate was 14%. Complications were most common when the
      Boyd procedure was used as a treatment strategy for congenital pseudoarthrosis of
      the tibia. Prosthetic management utilizing supramalleolar suspension with
      complete end-bearing through the residual limb was possible for the majority of
      cases. CONCLUSIONS: The Boyd procedure is an effective treatment for various
      conditions of the lower extremity. Concomitant or additional procedures after the
      initial intervention may be required for complete optimization of the residual
      limb. LEVEL OF EVIDENCE: Level IV.

PMID- 23872808
TI  - Si-enterobactin from the endophytic Streptomyces sp. KT-S1-B5--a potential
      silicon transporter in Nature?
AB  - Si-enterobactin (2a), a hexacoordinated complex of the siderophore enterobactin
      (2b) with silicon as the central atom, was isolated from an endophytic
      Streptomyces sp. occurring in Piper guinensis roots. The structure and absolute
      configuration were determined from NMR and MS data, and by X-ray diffraction. The
      orientation of the molecule along the pseudo-3-fold axis shows that the
      coordination environment of the silicon atom complexed with three bidentate
      ligands is Delta. We assume that 2a or related complexes may be involved in the
      transport of silicon in plants, diatoms, or other silicon-dependent organisms. 

PMID- 23872809
TI  - Correlations between chromatographic parameters and bioactivity predictors of
      potential herbicides.
AB  - Different liquid chromatography techniques, including reversed-phase liquid
      chromatography on Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester columns
      and micellar liqud chromatography with a Purosphere RP-8e column and using
      buffered sodium dodecyl sulfate-acetonitrile as the mobile phase, were applied to
      study the lipophilic properties of 15 newly synthesized phenoxyacetic and
      carbamic acid derivatives, which are potential herbicides. Chromatographic
      lipophilicity descriptors were used to extrapolate log k parameters (log kw and
      log km) and log k values. Partitioning lipophilicity descriptors, i.e., log P
      coefficients in an n-octanol-water system, were computed from the molecular
      structures of the tested compounds. Bioactivity descriptors, including partition
      coefficients in a water-plant cuticle system and water-human serum albumin and
      coefficients for human skin partition and permeation were calculated in silico by
      ACD/ADME software using the linear solvation energy relationship of Abraham.
      Principal component analysis was applied to describe similarities between various
      chromatographic and partitioning lipophilicities. Highly significant, predictive
      linear relationships were found between chromatographic parameters and
      bioactivity descriptors. 

PMID- 23872810
TI  - Halogen bonding in fluorine: experimental charge density study on intermolecular
      F...F and F...S donor-acceptor contacts.
AB  - The enigmatic type II C-F...F-C and C-F...S-C interactions in pentafluorophenyl
      2,2'-bithiazole are shown to be realistic "sigma-hole" interactions based on high
      resolution X-ray charge density analysis.

PMID- 23872811
TI  - Blackbody-mediated rotational laser cooling schemes in MgH+, DCl+, HCl+, LiH and
      CsH.
AB  - Ensembles of ultra-cold atoms, molecules and ions (both atomic and molecular) can
      be held in traps for increasingly long periods of time. While these trapped
      species remain translationally cold, for molecules the absorption of ambient
      black-body radiation can result in rapid thermalisation of the rotational (and
      vibrational) degrees of freedom. At 300 K, internal state purity is lost
      typically on the order of tens of seconds, inhibiting the study of quantum state
      selected reactions. In this paper a theoretical model is used to investigate
      laser-driven, blackbody-mediated, rotational cooling schemes for several (1)Sigma
      and (2)Pi diatomic species. The rotational cooling is particularly effective for
      DCl(+) and HCl(+), for which 92% and >99% (respectively) of the population can be
      driven into the rovibrational ground state. For the other systems a broadband
      optical pumping source (simultaneously exciting up to four transitions) is found
      to enhance the population that can be accumulated in the rovibrational ground
      state by up to 29% over that achieved when exciting a single transition. The
      influence of the rotational constant, dipole moments and electronic state of the
      diatomics on the rotational cooling achievable is also considered. An extension
      to polyatomic species is discussed and a combination of cold trap environments
      (at 77 K) and optical pumping schemes is proposed. 

PMID- 23872812
TI  - Update in pediatric optic neuritis.
AB  - PURPOSE OF REVIEW: Pediatric optic neuritis is an uncommon disorder with
      significant distinctions from its adult counterpart. Recognizing the features of
      this disorder and the potential association with progressive demyelinating
      processes is important for patients' evaluation and prognosis. RECENT FINDINGS:
      In the last few years, studies have expanded our understanding of demographic and
      presenting features for optic neuritis in the pediatric population. Emerging
      research on biomarkers and optical coherence tomography utility offers potential
      prognostic value in patient management. In addition, pooled research data have
      allowed for better understanding of the risks factors for progression from
      isolated optic neuritis to systemic demyelinating processes, such as multiple
      sclerosis. Although definitive evidence is lacking, corticosteroids remain the
      cornerstone of treatment. Various other immunosuppressive therapy studies have
      also reported success, particularly in refractory cases. SUMMARY: A comprehensive
      understanding of pediatric optic neuritis and its management remains elusive. A
      randomized clinical trial would potentially increase our knowledge and benefit
      the afflicted patients.

PMID- 23872813
TI  - Preschool vision screening: update on guidelines and techniques.
AB  - PURPOSE OF REVIEW: To discuss the current preschool vision screening (PVS)
      guidelines and review some of the newest vision screening techniques. The
      different vision screening practices and barriers to screening are discussed.
      RECENT FINDINGS: Vision screening guidelines, which have been developed in
      response to the advances in technology and increased understanding of the
      developing visual system, have been recently updated by some of the major medical
      organizations that endorse vision screening. With advances in vision screening
      technology, there is a growing trend for screening at younger ages. SUMMARY: PVS
      has been widely endorsed by various medical organizations as an effective way to
      detect preventable and treatable vision problems of childhood. Although PVS is
      widely recommended, actual screening rates remain low. There are several real and
      perceived barriers to screening which often prevents successful screening
      programs. Current vision screening guidelines take into account the recent
      advances in technology. With the development of new devices, vision screening can
      effectively be performed at younger ages.

PMID- 23872815
TI  - The coming age of enophthalmos.
AB  - PURPOSE OF REVIEW: Many factors are known to affect the health of the ocular
      surface. Enophthalmos is an often-overlooked component of ocular surface disease,
      and its prevalence is likely on the rise. This review outlines the many causes of
      enophthalmos, summarizes recent literature describing its relation to the health
      of the conjunctiva and cornea, and reviews new ways to treat it in clinical
      practice. RECENT FINDINGS: The terms giant fornix syndrome, senile sunken upper
      lids, and prostaglandin-associated periorbitopathy have recently been coined to
      describe newly recognized syndromes associated with enophthalmos. Many of these
      syndromes can lead to ocular surface disease and are becoming more prevalent as
      the population ages. SUMMARY: With an understanding of the causes of enophthalmos
      and its relation to the health of the ocular surface, an accurate diagnosis and
      treatment plan can be made for patients presenting with periorbital and ocular
      surface disease.

PMID- 23872814
TI  - Pediatric uveitis: new and future treatments.
AB  - PURPOSE OF REVIEW: Pediatric uveitis is relatively uncommon, accounting for only
      5-10% of all patients with uveitis. However, owing to high prevalence of
      complications and devastating outcomes, its lifetime burden can be significant.
      RECENT FINDINGS: Immunomodulatory therapy has been associated with better
      outcomes in noninfectious pediatric uveitis. However, effective treatments are
      limited by medication-related complications, including multiorgan toxicities and
      systemic side effects. SUMMARY: We review the current therapies available to
      treat pediatric uveitis, discuss novel and future therapies, and provide clinical
      recommendations utilizing these new agents. The consideration for treatment
      regimens in noninfectious pediatric uveitis is multifactorial. Understanding
      past, present, and future technology will aid in treatment of a complex and
      refractory disease.

PMID- 23872816
TI  - An update on ocular involvement in mucopolysaccharidoses.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on ocular
      manifestations of mucopolysaccharidoses (MPS), to highlight diagnostic pitfalls
      in the evaluation of affected patients, and to briefly review etiopathogenesis,
      systemic manifestations, and therapeutic interventions in MPS. RECENT FINDINGS:
      Advances in hematopoietic stem cell transplantation and enzyme replacement
      therapy for MPS have led to decreased morbidity and increased life-span of
      patients. Besides other causes, visual impairment because of corneal
      opacification, retinal degeneration, and optic atrophy remains a common cause of
      disability in MPS. The application of a standard ophthalmic evaluation protocol
      may serve as an important diagnostic and disease monitoring tool in patients.
      SUMMARY: Diagnostic delays are not uncommon in patients with MPS. Given the early
      ocular involvement in MPS, ophthalmologists play a crucial role in early
      detection and follow-up of patients with MPS. Ophthalmic evaluation can be
      impeded by corneal opacification and patient cooperation. Altered corneal
      biomechanics confound intraocular pressure measurements. Recently developed
      therapies have made early detection increasingly important. Accurate diagnosis of
      specific MPS subtypes is of paramount importance for initiating appropriate
      therapy. Combined with advances in supportive care of ocular and systemic
      manifestations, the prognosis for patients with MPS has vastly improved.

PMID- 23872817
TI  - Managing the patient with oculomotor nerve palsy.
AB  - PURPOSE OF REVIEW: To provide clinically relevant information regarding the
      evaluation and current treatment options for oculomotor nerve palsies. We survey
      recent literature and provide some insights into these studies. RECENT FINDINGS:
      Recent case reports highlight emerging new causes of oculomotor cranial nerve
      palsies, including sellar chordoma, odontogenic abscess, nonaneurysmal
      subarachnoid hemorrhage, polycythemia, sphenoiditis, neurobrucellosis,
      interpeduncular fossa lipoma, metastatic pancreatic cancer, leukemia, and
      lymphoma. Surgical studies have focused on modifications and innovations
      regarding strabismus surgery for this condition. New globe fixation procedures
      may include fixation to the medial orbital wall by precaruncular and
      retrocaruncular approaches, apically based orbital bone periosteal flap fixation
      and the suture/T-plate anchoring platform system. SUMMARY: Management of
      oculomotor nerve palsy depends in part upon the underlying cause and anatomical
      location of the lesion. Careful clinical evaluation and appropriate imaging can
      identify a definitive cause in most cases. Surgical options depend on the number,
      extent, and severity of the muscles involved as well as the presence or absence
      of signs of aberrant regeneration. The clinician should also address issues that
      arise due to involvement of the pupil and accommodation. Strabismus surgery can
      be challenging but also rewarding with appropriate selection and staging of
      procedures.

PMID- 23872818
TI  - Congenital cranial dysinnervation disorders: a concept in evolution.
AB  - PURPOSE OF REVIEW: We review the congenital and genetic diagnoses that are
      currently included in the congenital cranial dysinnervation disorders (CCDDs).
      RECENT FINDINGS: Recent literature contains new genotypic and phenotypic
      descriptions of Duane retraction syndrome, Moebius syndrome, and other CCDDs. New
      genes which when mutated can result in CCDD have been identified, permitting a
      better understanding of associated phenotypes. More information is available
      regarding neurodevelopmental and clinical effects of various gene mutations
      associated with individual CCDDs. For certain CCDDs, the phenotype of a
      particular individual may not completely predict the genotype, and conversely,
      the genotype may not always predict the phenotype. SUMMARY: The CCDD concept has
      focused attention on specific congenital disturbances of human ocular motility
      and on the fact that these disorders are typically neurogenic in origin. The past
      decade has seen rapid evolution within this field with the last 2 years yielding
      additional information about existing diagnoses, genes, and phenotypes that may
      result in better classification of these disorders and new genotype-phenotype
      correlations in the future.

PMID- 23872819
TI  - Telemedicine for retinopathy of prematurity.
AB  - PURPOSE OF REVIEW: To examine and review digital retinal imaging via telemedicine
      as an important screening and diagnostic tool in the management of retinopathy of
      prematurity (ROP). RECENT FINDINGS: The use of wide-angle digital retinal
      photography to detect clinically significant ROP has been described in numerous
      reports since 2000. Comparisons with the gold standard of binocular indirect
      ophthalmoscopy have been favorable. Digital image capture can provide more
      objective information for disease detection, thereby facilitating internet
      consultation and retrospective analysis as part of the electronic medical record.
      As the presence of plus disease in ROP is now the most important criteria for
      determining the need for laser treatment, computer-based image analysis can
      potentially provide additional benefit to digital retinal imaging. Telemedicine
      screening also allows for the extension of diagnostic expertise to underserved
      areas in both the developed and third world. The role of telemedicine in ROP
      education will impact both screening efforts and traditional fellowship training
      in future years. SUMMARY: As the worldwide incidence of ROP continues to rise,
      the use of telemedicine for screening, diagnostic and educational purposes will
      assume increasing importance in the delivery of healthcare for premature infants.

PMID- 23872821
TI  - Longer term effects of total knee arthroplasty from a national longitudinal
      study.
AB  - OBJECTIVE: This study used data for 1996-2010 from a U.S. longitudinal sample of
      elderly individuals from the Health and Retirement Study (HRS) merged with
      Medicare claims data to assess changes in several dimensions of physical
      functioning and general health up to 68 months following total knee arthroplasty
      (TKA) receipt. METHOD: Using propensity score matching, we assessed outcomes at
      follow-up for Medicare beneficiaries receiving TKA and a comparable group of
      beneficiaries with the same osteoarthritis diagnoses (controls). RESULTS: Receipt
      of TKA was most often associated with improvements in physical functioning,
      especially in physical functioning measures most directly related to the knee.
      General health of TKA recipients only improved relative to controls on 1 of the 3
      study general health measures. DISCUSSION: Improvements in physical functioning
      of TKA recipients persisted in this longer term analysis of outcome in a
      nationally representative population study.

PMID- 23872822
TI  - Health impacts of caregiving for older adults with functional limitations:
      results from the Singapore survey on informal caregiving.
AB  - OBJECTIVE: To estimate the health impact, in terms of depression, self-rated
      health, and health services utilization, of providing care to older adults (75+)
      requiring human assistance in at least one activity of daily living (ADL)
      limitation. METHOD: Data from 1,077 caregivers and 318 noncaregivers, interviewed
      in the Singapore Survey on Informal Caregiving, was used to examine differences
      in depressive symptoms, self-rated health, and number of outpatient visits in the
      last 1 month between caregivers and noncaregivers. Multivariate models for the
      outcomes, adjusting for characteristics of the caregiver/noncaregiver and care
      recipient/potential care recipient, were run. RESULTS: Caregivers were more
      depressed, had poorer self-rated health, and had a higher rate of outpatient
      visits in the past month compared to noncaregivers. DISCUSSION: The study
      indicates the need for support services to family caregivers of older adults with
      ADL limitations.

PMID- 23872823
TI  - The association between mid-life socioeconomic position and health after
      retirement--exploring the role of working conditions.
AB  - OBJECTIVE: To explore the role of working conditions in the association between
      socioeconomic position and health after retirement age using over 20 years follow
      up. METHOD: Two Swedish nationally representative Level of Living Surveys (total
      N = 1,131) were used. Ordered logistic regression was used to assess the
      association between socioeconomic position and health (self-rated health,
      psychological distress, musculoskeletal pain, circulatory problems, physical and
      cognitive impairment). The role of physical and psychological working conditions
      was also assessed. RESULTS: Lower socioeconomic position was associated with more
      adverse physical, but not psychological, working conditions. Physical working
      conditions partially explained the differences in physical impairment and
      musculoskeletal pain in old age attributed to socioeconomic position, but not
      differences in self-rated health, circulatory problems, psychological distress,
      and cognitive impairment. Socioeconomic position was a stronger correlate of
      health than psychological working conditions alone. DISCUSSION: Improving
      physical working conditions may be important for reducing the influence of
      socioeconomic position on health after retirement.

PMID- 23872824
TI  - A randomised study of the effect of danoprevir/ritonavir or ritonavir on
      substrates of cytochrome P450 (CYP) 3A and 2C9 in chronic hepatitis C patients
      using a drug cocktail.
AB  - PURPOSE: The aim of this study was to evaluate the effects of danoprevir in
      combination with low-dose ritonavir (danoprevir/r) and placebo plus low-dose
      ritonavir on the pharmacokinetics of probe drugs for cytochrome P450 (CYP) 3A and
      CYP2C9, in patients with chronic hepatitis C. METHODS: A total of 54 patients
      infected with hepatitis C virus genotype 1 received an oral drug cocktail (2 mg
      midazolam, 10 mg warfarin and 10 mg vitamin K) before and after 14 days of dosing
      with either danoprevir/r or placebo plus low-dose ritonavir (placebo/r). Serial
      pharmacokinetic samples were collected up to 24 (midazolam) and 72 (S-warfarin) h
      post-dose. Plasma concentrations of midazolam, alpha-hydroxymidazolam and S
      warfarin were measured using validated assays. Pharmacokinetic parameters were
      estimated using non-compartmental analysis, and geometric mean ratios (GMRs) and
      90 % confidence intervals (CIs) for the differences between baseline and post
      dosing values were calculated. RESULTS: Danoprevir/r and placebo/r significantly
      increased midazolam area under the time-concentration curve (AUC0-infinity) and
      reduced the midazolam metabolic ratio while S-warfarin AUC0-infinity was modestly
      decreased. When danoprevir data were pooled across doses, the midazolam GMR (90 %
      CI) AUC0-infinity was 9.41 (8.11, 10.9) and 11.14 (9.42, 13.2) following
      danoprevir/r and placebo/r dosing, respectively, and the S-warfarin GMR (90 % CI)
      AUC0-infinity was 0.72 (0.68, 0.76) and 0.76 (0.69, 0.85), respectively. The
      effects of danoprevir/r and placebo/r appeared to be qualitatively similar.
      CONCLUSIONS: Substantial inhibition of CYP3A- and modest induction of CYP2C9-
      activity were observed with danoprevir/r and low-dose ritonavir.

PMID- 23872826
TI  - Genomic medicine, precision medicine, personalized medicine: what's in a name?
AB  - This issue of Clinical Pharmacology & Therapeutics is devoted to genomic
      medicine, and a reader may reasonably ask what we mean when we use those words.
      In the initial issue of the journal Genomics in 1987, McKusick and Ruddle pointed
      out that the descriptor "genome" had been coined in 1920 as a hybrid of "gene"
      and "chromosome," and that their new journal would focus on the "newly-developing
      discipline of mapping/sequencing (including analysis of the information)." A key
      milestone in the field was the generation of the first draft of a human genome in
      2000, but this success really represents only one of many milestones in the
      journey from Mendel to MiSeq. 

PMID- 23872829
TI  - The opportunities and challenges of implementing genomics-informed personalized
      medicine.

PMID- 23872830
TI  - CYP2D6 genotype should not be used to determine endocrine therapy in
      postmenopausal breast cancer patients.

PMID- 23872831
TI  - CYP2D6 genotype and tamoxifen activity: understanding interstudy variability in
      methodological quality.

PMID- 23872832
TI  - Genomic medicine: too great expectations?
AB  - As advances in genomic medicine have captured the interest and enthusiasm of the
      public, an unintended consequence has been the creation of unrealistic
      expectations. Because these expectations may have a negative impact on
      individuals as well as genomics in general, it is important that they be
      understood and confronted. 

PMID- 23872833
TI  - Genomic testing: the clinical laboratory perspective.
AB  - The expansion of genetic testing in the clinical laboratory is well under way,
      with many clinically validated genetic tests already in use. As sequencing
      technology becomes more efficient and less costly, clinical laboratories will
      make the transition from single-gene testing to multigene panels. Early, more
      targeted applications will gradually be replaced by more comprehensive genomic
      offerings, including exome and whole-genome analysis. Despite significant
      technological advancements, many obstacles remain for full incorporation of whole
      genome testing. 

PMID- 23872834
TI  - Educational challenges in implementing genomic medicine.
AB  - Clinical medicine is about to embark on an exciting, although harrowing, period
      of innovation, the result of astonishing advances in genomic science. The current
      workforce--physicians, nurses, pharmacists, and others--will soon need to adapt
      to substantial change, driven by genomics, in diagnostic and therapeutic
      strategies. If errors of omission and commission are to be prevented, sustained
      efforts in workforce education will be needed on the part of medical schools,
      training programs, and professional societies.

PMID- 23872835
TI  - Regulatory challenges in the review of data from global clinical trials: the PMDA
      perspective.
AB  - Regulatory agencies face challenges in reviewing data from global clinical trials
      (GCTs) in the era of globalization of drug development. One major challenge is
      consideration of ethnic factors in evaluating GCT data so as to extrapolate
      foreign population data to one's own national population. Here, we present the
      Pharmaceuticals and Medical Devices Agency (PMDA) perspective in reviewing GCT
      data in new drug applications (NDAs) and discuss future challenges for new drug
      approval. 

PMID- 23872836
TI  - Genetics of cisplatin ototoxicity: confirming the unexplained?
AB  - Replication of findings in clinical pharmacogenetic studies is essential but
      often neglected. The observation that TPMT and COMT genotypes, in combination
      with ABCC3 genotype, are predictive of ototoxicity following cisplatin treatment
      has been confirmed. However, translating this observation into a useful
      preventive strategy requires more mechanistic insight. 

PMID- 23872837
TI  - The effect of agar jelly on energy expenditure, appetite, gastric emptying and
      glycaemic response.
AB  - BACKGROUND AND PURPOSE: Agar contains a high amount of soluble fibre and has been
      shown to delay gastric emptying (GE) without impacting on glycaemic response
      (GR). The current study aimed to further the limited data on the effect of agar
      on metabolism by assessing the effects on GE and GR as well as appetite- and diet
      induced thermogenesis (DIT). METHODS: In this randomized control trial, eleven
      healthy volunteers were tested on two occasions following an overnight fast.
      Following baseline and resting measurements, volunteers were either fed a fruit
      flavoured drink (liquid) or consumed a fruit-flavoured jelly (jelly). The two
      were exactly the same in composition except the jelly contained 4 g of agar
      crystals. Both contained 50 g of available carbohydrate. DIT was measured using
      indirect calorimetry, GE using the (13)C sodium acetate breath test, appetite
      using visual analogue scale and GR using finger prick blood samples. RESULTS: The
      jelly significantly delayed GE across all time points-latency phase (p = 0.07),
      lag phase (p = 0.04), half-time (p < 0.0001), ascension time (p = 0.025). The
      jelly also increased all appetite parameters-hunger (p = 0.006), fullness (p =
      0.035), desire to eat (p = 0.03) and prospective consumption (p = 0.011).
      However, there were no significant differences in either GR or postprandial DIT
      between the liquid and jelly. CONCLUSION: Agar delays GE and increases appetite
      but does not change GR or DIT most probably due to the increase in viscosity
      caused by the agar jelly.

PMID- 23872838
TI  - Observation of Dirac plasmons in a topological insulator.
AB  - Plasmons are quantized collective oscillations of electrons and have been
      observed in metals and doped semiconductors. The plasmons of ordinary, massive
      electrons have been the basic ingredients of research in plasmonics and in
      optical metamaterials for a long time. However, plasmons of massless Dirac
      electrons have only recently been observed in graphene, a purely two-dimensional
      electron system. Their properties are promising for novel tunable plasmonic
      metamaterials in the terahertz and mid-infrared frequency range. Dirac fermions
      also occur in the two-dimensional electron gas that forms at the surface of
      topological insulators as a result of the strong spin-orbit interaction existing
      in the insulating bulk phase. One may therefore look for their collective
      excitations using infrared spectroscopy. Here we report the first experimental
      evidence of plasmonic excitations in a topological insulator (Bi2Se3). The
      material was prepared in thin micro-ribbon arrays of different widths W and
      periods 2W to select suitable values of the plasmon wavevector k. The linewidth
      of the plasmon was found to remain nearly constant at temperatures between 6 K
      and 300 K, as expected when exciting topological carriers. Moreover, by changing
      W and measuring the plasmon frequency in the terahertz range versus k we show,
      without using any fitting parameter, that the dispersion curve agrees
      quantitatively with that predicted for Dirac plasmons.

PMID- 23872839
TI  - A novel mechanism for antiglycative action of limonene through stabilization of
      protein conformation.
AB  - Inhibition of protein glycation is known to ameliorate secondary complications in
      diabetes. In the present study antiglycative properties of limonene, a natural
      product, were evaluated using BSA as a model protein. AMG (aminoguanidine) was
      used as a positive control. Measurement of total AGEs (Advanced Glycation End
      products) and specific AGEs revealed that limonene could inhibit protein
      glycation to the extent of 56.3% and 75.1% respectively at 50 MUM concentration
      as against 54.4% and 82.2% by AMG at 1 mM. Congo red binding and CD (Circular
      Dichroism) analysis revealed inhibition of alpha-helix to beta-sheet transition
      wherein 18.5% beta-sheet structures were observed in glycated BSA (bovine serum
      albumin) as against 4.9% with limonene. Glycation of protein in the presence of
      urea was enhanced by 18%, while in the presence of limonene it was reduced by 23%
      revealing the stabilizing effect of limonene. Electrophoretic mobility was
      similar to the normal control and a zeta potential value of -12.1 mV as against 
      15.1 mV in diabetic control was observed. Inhibition of glycation in limonene
      treated samples was confirmed through LC-MS analysis wherein AGEs such as
      pentosidine, CML (N(epsilon)-(carboxymethyl)lysine), CEL (N(epsilon)
      (carboxyethyl)lysine), MOLD (methylglyoxal-lysine dimer) and imidazolone observed
      in glycated samples were absent in limonene treated samples. PatchDock studies
      revealed that limonene could bind to the major glycation sites IB, IIA and IIB
      sub domains and AMG to the IIIA sub domain. Thus limonene is a potent protein
      glycation inhibitor that prevents protein glycation through a novel mechanism of
      stabilization of protein structure through hydrophobic interactions.

PMID- 23872840
TI  - Identification of unknown homeopathic remedies by delayed luminescence.
AB  - A quality control method of highly diluted and potentized homeopathic remedies is
      important for curing patients applying homeopathic therapy. Lenger detected
      photons in highly potentized homeopathic remedies by delayed luminescence. The
      photons of Argentum metallicum 100MK and Cantharis 100MK magnetically bound to
      their carrier substances ethanol or saccharose were separated by their resonating
      magnetic field of about 2.06 MHz. The photons of these 100MK potency levels and
      of their reference substances were determined to be standard values calculated by
      the B2-values of Bajpai's equation derived from the Hamiltonian equation. The
      stability of ethanolic Argentum metallicum 100MK and Cantharis 100MK declined to
      1/3 of their photons within a month in contrast to saccharose globules with
      Argentum metallicum 100MK having been stable during the period of these
      investigations for almost 1 year. Some remedies delivered as CMK potency had been
      proved to be ethanol. The testing amount of high ethanolic potencies is limited
      to 40 MUl because 80 MUl resulted in an attenuation of the photons; 40 MUl equal
      16 medicated saccharose globules. Six unknown homeopathic remedies could be
      identified as increasing potency levels of Argentum metallicum from 100MK to
      1.000MK which indicates a calibration curve. The homeopathic factories having
      sent the unknown remedies confirmed the measurements. A quality control of
      homeopathic remedies is possible by comparing the different B2-values of the
      remedies and their carrier substances.

PMID- 23872841
TI  - Reactivity landscape of pyruvate under simulated hydrothermal vent conditions.
AB  - Pyruvate is an important "hub" metabolite that is a precursor for amino acids,
      sugars, cofactors, and lipids in extant metabolic networks. Pyruvate has been
      produced under simulated hydrothermal vent conditions from alkyl thiols and
      carbon monoxide in the presence of transition metal sulfides at 250  degrees C
      [Cody GD et al. (2000) Science 289(5483):1337-1340], so it is plausible that
      pyruvate was formed in hydrothermal systems on the early earth. We report here
      that pyruvate reacts readily in the presence of transition metal sulfide minerals
      under simulated hydrothermal vent fluids at more moderate temperatures (25-110 
      degrees C) that are more conducive to survival of biogenic molecules. We found
      that pyruvate partitions among five reaction pathways at rates that depend upon
      the nature of the mineral present; the concentrations of H2S, H2, and NH4Cl; and
      the temperature. In most cases, high yields of one or two primary products are
      found due to preferential acceleration of certain pathways. Reactions observed
      include reduction of ketones to alcohols and aldol condensation, both reactions
      that are common in extant metabolic networks. We also observed reductive
      amination to form alanine and reduction to form propionic acid. Amino acids and
      fatty acids formed by analogous processes may have been important components of a
      protometabolic network that allowed the emergence of life. 

PMID- 23872842
TI  - Drops on soft surfaces learn the hard way.

PMID- 23872843
TI  - Oncogenic herpesviruses sending mixed signals.

PMID- 23872844
TI  - Neutrophils enlist IL-22 to restore order in the gut.

PMID- 23872845
TI  - Integrated biophysical approach to fragment screening and validation for fragment
      based lead discovery.
AB  - In fragment-based drug discovery, the weak affinities exhibited by fragments pose
      significant challenges for screening. Biophysical techniques are used to address
      this challenge, but there is no clear consensus on which cascade of methods is
      best suited to identify fragment hits that ultimately translate into bound X-ray
      structures and provide bona fide starting points for synthesis. We have
      benchmarked an integrated biophysical approach for fragment screening and
      validation against Mycobacterium tuberculosis pantothenate synthetase. A primary
      screen of 1,250 fragments library was performed by thermal shift, followed by
      secondary screen using one-dimensional NMR spectroscopy (water ligand observed
      gradient spectroscopy and saturation transfer difference binding experiments) and
      ultimate hit validation by isothermal titration calorimetry and X-ray
      crystallography. Our multibiophysical approach identified three distinct binding
      sites for fragments and laid a solid foundation for successful structure-based
      elaboration into potent inhibitors. 

PMID- 23872848
TI  - Production and optimization of poly-gamma-glutamic acid by Bacillus subtilis BL53
      isolated from the Amazonian environment.
AB  - The aims of this research were to screen and characterize a new microbial source
      of gamma-PGA, to optimize aspects of culture conditions and medium composition
      using central composite design and response surface methodologies. The influence
      of bioreactor stirring rates on the production of gamma-PGA was also investigated
      and the oxygen volumetric mass transfer coefficients (k La) were established. The
      most productive strain was identified by 16S rDNA analysis as Bacillus subtilis,
      and its gamma-PGA production in rotatory shaker was threefold increased under
      optimized conditions (37  degrees C, pH 6.9, and 1.22 mM Zn(2+)), compared to
      conventional medium. In bioreactor, the gamma-PGA production was further
      increased, reaching 17 g l(-1), 70 % higher than shaker cultures. gamma-PGA
      production showed high dependency on oxygen transfer. At k La of 210 h(-1), the
      cultivation time could be reduced to 48 h, about 50 % of the time required for
      operations at k La 55 h(-1). 

PMID- 23872846
TI  - Structural insights into the proton pumping by unusual proteorhodopsin from
      nonmarine bacteria.
AB  - Light-driven proton pumps are present in many organisms. Here, we present a high
      resolution structure of a proteorhodopsin from a permafrost bacterium,
      Exiguobacterium sibiricum rhodopsin (ESR). Contrary to the proton pumps of known
      structure, ESR possesses three unique features. First, ESR's proton donor is a
      lysine side chain that is situated very close to the bulk solvent. Second, the
      alpha-helical structure in the middle of the helix F is replaced by 3(10)- and pi
      helix-like elements that are stabilized by the Trp-154 and Asn-224 side chains.
      This feature is characteristic for the proteorhodopsin family of proteins. Third,
      the proton release region is connected to the bulk solvent by a chain of water
      molecules already in the ground state. Despite these peculiarities, the positions
      of water molecule and amino acid side chains in the immediate Schiff base
      vicinity are very well conserved. These features make ESR a very unusual proton
      pump. The presented structure sheds light on the large family of
      proteorhodopsins, for which structural information was not available previously.

PMID- 23872849
TI  - The regulation of 2,3-butanediol synthesis in Klebsiella pneumoniae as revealed
      by gene over-expressions and metabolic flux analysis.
AB  - A variety of microorganism species are able naturally to produce 2,3-butanediol
      (2,3-BDO), although only a few of them are suitable for consideration as having
      potential for mass production purposes. Klebsiella pneumoniae (K. pneumoniae) is
      one such strain which has been widely studied and used industrially to produce
      2,3-BDO. In the central carbon metabolism of K. pneumoniae, the 2,3-BDO synthesis
      pathway is dominated by three essential enzymes, namely acetolactate
      decarboxylase, acetolactate synthase, and butanediol dehydrogenase, which are
      encoded by the budA, budB, and budC genes, respectively. The mechanisms of the
      three enzymes have been characterized with regard to their function and roles in
      2,3-BDO synthesis and cell growth (Blomqvist et al. in J Bacteriol 175(5):1392
      1404, 1993), while a few studies have focused on the cooperative mechanisms of
      the three enzymes and their mutual interactions. Therefore, the K. pneumoniae
      KCTC2242::DeltawabG wild-type strain was utilized to reconstruct seven new
      mutants by single, double, and triple overexpression of the three enzymes key to
      this study. Subsequently, continuous cultures were performed to obtain steady
      state metabolism in the organisms and experimental data were analyzed by
      metabolic flux analysis (MFA) to determine the regulation mechanisms. The MFA
      results showed that the seven overexpressed mutants all exhibited enhanced 2,3
      BDO production, and the strain overexpressing the budBA gene produced the highest
      yield. While the enzyme encoded by the budA gene produced branched-chain amino
      acids which were favorable for cell growth, the budB gene enzyme rapidly enhanced
      the conversion of acetolactate to acetoin in an oxygen-dependent manner, and the
      budC gene enzyme catalyzed the reversible conversion of acetoin to 2,3-BDO and
      regulated the intracellular NAD(+)/NADH balance. 

PMID- 23872847
TI  - Targeting H3K4 trimethylation in Huntington disease.
AB  - Transcriptional dysregulation is an early feature of Huntington disease (HD). We
      observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at
      transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome
      wide analysis showed a chromatin signature for this mark. Reducing the levels of
      the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of
      key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of
      SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a
      Drosophila HD model was protective. Therefore, targeting this epigenetic
      signature may be an effective strategy to ameliorate the consequences of HD. 

PMID- 23872850
TI  - 3D alkyne-azide cycloaddition: spatiotemporally controlled by combination of aryl
      azide photochemistry and two-photon grafting.
AB  - A novel fluoroaryl azide with an alkyne tail was synthesized and precisely
      immobilized within a PEG-based matrix via two-photon induced decomposition and
      nitrene insertion. Well defined 3D positioning of the terminal alkyne allows site
      specific micropatterning. The subsequent 3D alkyne-azide cycloaddition was
      realized using dye-functionalized molecules containing "clickable" azide
      moieties. 

PMID- 23872851
TI  - Quantifying uncertainties in the microvascular transport of nanoparticles.
AB  - The character of nanoparticle dispersion in the microvasculature is a driving
      factor in nanoparticle-based therapeutics and bio-sensing. It is difficult, with
      current experimental and engineering capability, to understand dispersion of
      nanoparticles because their vascular system is more complex than mouse models and
      because nanoparticle dispersion is so sensitive to in vivo environments.
      Furthermore, uncertainty cannot be ignored due to the high variation of location
      specific vessel characteristics as well as variation across patients. In this
      paper, a computational method that considers uncertainty is developed to predict
      nanoparticle dispersion and transport characteristics in the microvasculature
      with a three step process. First, a computer simulation method is developed to
      predict blood flow and the dispersion of nanoparticles in the microvessels.
      Second, experiments for nanoparticle dispersion coefficients are combined with
      results from the computer model to suggest the true values of its unknown and
      unmeasurable parameters-red blood cell deformability and red blood cell
      interaction-using the Bayesian statistical framework. Third, quantitative
      predictions for nanoparticle transport in the tumor microvasculature are made
      that consider uncertainty in the vessel diameter, flow velocity, and hematocrit.
      Our results show that nanoparticle transport is highly sensitive to the
      microvasculature. 

PMID- 23872852
TI  - Treatment of collateral channel perforation during percutaneous coronary
      intervention for chronic total occlusion with retrograde approach.
AB  - We describe one case of septal and two cases of epicardial collateral channel
      perforation during percutaneous coronary intervention by the retrograde approach
      for chronic total occlusion. After coil embolization of the channel perforation
      area, additional treatments were required in all three cases to stop bleeding.
      All three cases required injection of autologous clots, with one case also
      requiring subsequent injection of fibrin glue. 

PMID- 23872853
TI  - Co-infection by alveolate parasites and frog virus 3-like ranavirus during an
      amphibian larval mortality event in Florida, USA.
AB  - A multispecies amphibian larval mortality event, primarily affecting American
      bullfrogs Lithobates catesbeianus, was investigated during April 2011 at the Mike
      Roess Gold Head Branch State Park, Clay County, Florida, USA. Freshly dead and
      moribund tadpoles had hemorrhagic lesions around the vent and on the ventral body
      surface, with some exhibiting a swollen abdomen. Bullfrogs (100%), southern
      leopard frogs L. sphenocephalus (33.3%), and gopher frogs L. capito (100%) were
      infected by alveolate parasites. The intensity of infection in bullfrog livers
      was high. Tadpoles were evaluated for frog virus 3 (FV3) by histology and PCR.
      For those southern leopard frog tadpoles (n = 2) whose livers had not been
      obscured by alveolate spore infection, neither a pathologic response nor
      intracytoplasmic inclusions typically associated with clinical infections of FV3
      like ranavirus were noted. Sequencing of a portion (496 bp) of the viral major
      capsid protein gene confirmed FV3-like virus in bullfrogs (n = 1, plus n = 6
      pooled) and southern leopard frogs (n = 1, plus n = 4 pooled). In July 2011,
      young-of-the-year bullfrog tadpoles (n = 7) were negative for alveolate
      parasites, but 1 gopher frog tadpole was positive. To our knowledge, this is the
      first confirmed mortality event for amphibians in Florida associated with FV3
      like virus, but the extent to which the virus played a primary role is uncertain.
      Larval mortality was most likely caused by a combination of alveolate parasite
      infections, FV3-like ranavirus, and undetermined etiological factors. 

PMID- 23872854
TI  - Epidemiology of cyprinid herpesvirus-3 infection in latently infected carp from
      aquaculture.
AB  - Cyprinid herpesvirus-3 (CyHV-3, koi herpesvirus, KHV) is the causative agent of
      an economically important disease in carp. The mode of transmission of this
      virus, especially how the infectious agent is introduced into ponds de novo, is
      not known in detail. The aim of this study was to investigate the shedding of
      CyHV-3 from fish with latent infections, under aquaculture conditions. Ponds in
      Saxony, Germany, with latently infected carp were examined at different times
      during the production cycle to investigate the influence of fish farming
      procedures on virus activation and shedding. Carp and water samples were
      investigated by quantitative real-time PCR. Some of the latently infected carp
      shed CyHV-3. Virus shedding was induced mainly when the ponds were drained and
      the carp either harvested or moved to different ponds, and was independent of the
      water temperature. This indicated that during these times there was a risk that
      effluent water from the ponds could disseminate the infectious agent. During
      summer, on-growing carp are infected with low numbers of CyHV-3. These findings
      are important for disease management strategies in carp aquaculture and for the
      design of testing protocols for the detection of latent infection in carp
      populations. 

PMID- 23872855
TI  - Identification and characterisation of an ostreid herpesvirus-1 microvariant
      (OsHV-1 u-var) in Crassostrea gigas (Pacific oysters) in Australia.
AB  - Between November 2010 and January 2011, triploid Crassostrea gigas (Pacific
      oysters) cultivated in the Georges River, New South Wales, experienced >95%
      mortality. Mortalities also occurred in wild diploid C. gigas in the Georges
      River and shortly thereafter in the adjacent Parramatta River estuary upstream
      from Sydney Harbour. Neighbouring Saccostrea glomerata (Sydney rock oysters) did
      not experience mortalities in either estuary. Surviving oysters were collected to
      investigate the cause of mortalities. Histologically all oysters displayed
      significant pathology, and molecular testing revealed a high prevalence of
      ostreid herpesvirus-1 (OsHV-1). Quantitative PCR indicated that many C. gigas
      were carrying a high viral load at the time of sampling, while the load in S.
      glomerata was significantly lower (p < 0.001). Subsequent in situ hybridisation
      experiments confirmed the presence of a herpesvirus in C. gigas but not S.
      glomerata tissues, suggesting that S. glomerata is not susceptible to infection
      with OsHV-1. Naive sentinel triploid C. gigas placed in the Georges River estuary
      in January 2011 quickly became infected and experienced nearly 100% mortality
      within 2 wk of exposure, indicating the persistence of the virus in the
      environment. Phylogenetic analysis of sequences derived from the C2/C6 region of
      the virus revealed that the Australian strain of OsHV-1 belongs to the
      microvariant (u-var) cluster, which has been associated with severe mortalities
      in C. gigas in other countries since 2008. Environmental data revealed that the
      Woolooware Bay outbreaks occurred during a time of considerable environmental
      disturbance, with increased water temperatures, heavy rainfall, a toxic
      phytoplankton bloom and the presence of a pathogenic Vibrio sp. all potentially
      contributing to oyster stress. This is the first confirmed report of OsHV-1 u-var
      related C. gigas mortalities in Australia.

PMID- 23872856
TI  - Spatial distribution of mortality in Pacific oysters Crassostrea gigas:
      reflection on mechanisms of OsHV-1 transmission.
AB  - The ostreid herpesvirus OsHV-1 has the potential to devastate Pacific oyster
      Crassostrea gigas culture in Australia as it has done in many other countries,
      highlighting the need for a better understanding of disease expression and
      transmission. The aim of this study was to assess the spatial distribution of
      OsHV-1-associated mortalities in one of only two infected areas in Australia,
      Woolooware Bay (Botany Bay, New South Wales). In October 2011, healthy sentinel
      Pacific oysters were placed in 3 different locations at 3 different tidal levels,
      and OsHV-1 associated mortalities were closely monitored over 7 mo. The outbreak
      started in November 2011, and the disease remained active until April 2012. Three
      major mortality events were detected. Rather than being a propagating epizootic,
      it appeared that most oysters were infected from a common environmental source.
      The distribution of OsHV-1-associated mortalities was spatially clustered, highly
      variable and clearly dependent on the age of oysters and their position in the
      water column. Non-random distribution of mortalities at macro scale (sites
      several km apart) and micro scale (within rearing trays), and vertical clustering
      patterns in the water column are discussed in regard to factors known to
      influence mechanism of disease transmission in aquatic environments
      (hydrodynamics, physical disturbances, host density/distribution, and variations
      of environmental parameters). A new hypothesis proposing that OsHV-1 may be
      carried through water by particles, possibly plankton, is also suggested to
      explain the patchy distribution of mortalities in Woolooware Bay. 

PMID- 23872857
TI  - Parasitic infection by larval helminths in Antarctic fishes: pathological changes
      and impact on the host body condition index.
AB  - We examined pathological changes and relationship between body condition index
      (BCI) and parasitic infection in 5 species of fish, including 42 icefish
      Chionodraco hamatus (Channichtyidae), 2 dragonfish Cygnodraco mawsoni
      (Bathydraconidae), 30 emerald rock cod Trematomus bernacchii, 46 striped rock cod
      T. hansoni and 9 dusty rock cod T. newnesi (Nototheniidae) from the Ross Sea,
      Antarctica. All parasites were identified by a combination of morphology and
      mtDNA cytochrome-oxidase-2 sequence (mtDNA cox2) analysis, except Contracaecum
      osculatum s.l., for which only the latter was used. Five larval taxa were
      associated with pathological changes including 2 sibling species (D and E) of the
      C. osculatum species complex and 3 cestodes including plerocercoids of a
      diphyllobothridean, and 2 tetraphyllidean forms including cercoids with
      monolocular and bilocular bothridia. The most heavily infected hosts were C.
      hamatus and C. mawsoni, with C. hamatus most often infected by C. osculatum sp. D
      and sp. E and diphyllobothrideans, while C. mawsoni was most often infected with
      tetraphyllidean forms. Histologically, all fish showed varying severity of
      chronic inflammation associated with larval forms of helminths.
      Diphyllobothrideans and C. osculatum spp. were located in gastric muscularis or
      liver and were associated with necrosis and mild to marked fibrosis. Moderate
      multifocal rectal mucosal chronic inflammation was associated with attached
      tetraphyllidean scolices. C. hamatus showed a strong negative correlation between
      BCI and parasite burden.

PMID- 23872858
TI  - Sea lice infestations on juvenile chum and pink salmon in the Broughton
      Archipelago, Canada, from 2003 to 2012.
AB  - Juvenile pink salmon Oncorhynchus gorbuscha and chum salmon O. keta were sampled
      by beach or purse seine to assess levels of sea lice infestation in the Knight
      Inlet and Broughton Archipelago regions of coastal British Columbia, Canada,
      during the months of March to July from 2003 to 2012. Beach seine data were
      analyzed for sea lice infestation that was described in terms of prevalence,
      abundance, intensity, and intensity per unit length. The median annual prevalence
      for chum was 30%, ranging from 14% (in 2008 and 2009) to 73% (in 2004), while for
      pink salmon, the median was 27% and ranged from 10% (in 2011) to 68% (in 2004).
      Annual abundance varied from 0.2 to 5 sea lice per fish with a median of 0.47 for
      chum and from 0.1 to 3 lice (median 0.42) for pink salmon. Annual infestation
      followed broadly similar trends for both chum and pink salmon. However, the
      abundance and intensity of Lepeophtheirus salmonis and Caligus clemensi, the 2
      main sea lice species of interest, were significantly greater on chum than on
      pink salmon in around half of the years studied. Logistic regression with random
      effect was used to model prevalence of sea lice infestation for the combined
      beach and purse seine data. The model suggested inter-annual variation as well as
      a spatial clustering effect on the prevalence of sea lice infestation in both
      chum and pink salmon. Fish length had an effect on prevalence, although the
      nature of this effect differed according to host species.

PMID- 23872860
TI  - Update on the diagnosis and classification of ILD.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the
      diagnosis and classification of interstitial lung disease (ILD), with a specific
      focus on newly described ILD subtypes and phenotypes. In addition, the strengths
      and limitations of the current approach to ILD diagnosis and management are
      discussed. RECENT FINDINGS: Idiopathic pleuroparenchymal fibroelastosis and acute
      fibrinous and organizing pneumonia are new entities that have been described in
      small case series. Undifferentiated connective tissue disease-associated ILD,
      smoking-related interstitial fibrosis, familial ILD, unclassifiable ILD, and
      subclinical ILD have also been better characterized in recent publications. New
      data regarding these conditions are summarized in this review. The
      multidisciplinary approach to ILD is reviewed, and complementary classification
      schemes are described that may help direct the management and improve
      prognostication of some ILDs. SUMMARY: ILDs are a large and heterogeneous group
      of diseases with several newly characterized subtypes and phenotypes. The current
      approach to ILD classification has limitations in some patients that can be
      minimized by considering complementary classification schemes.

PMID- 23872859
TI  - CyHV-3: the third cyprinid herpesvirus.
AB  - Common carp (including ornamental koi carp) Cyprinus carpio L. are ecologically
      and economically important freshwater fish in Europe and Asia. C. carpio have
      recently been endangered by a third cyprinid herpesvirus, known as cyprinid
      herpesvirus-3 (CyHV-3), the etiological agent of koi herpesvirus disease (KHVD),
      which causes significant morbidity and mortality in koi and common carp. Clinical
      and pathological signs include epidermal abrasions, excess mucus production,
      necrosis of gill and internal organs, and lethargy. KHVD has decimated major carp
      populations in Israel, Indonesia, Taiwan, Japan, Germany, Canada, and the USA,
      and has been listed as a notifiable disease in Germany since 2005, and by the
      World Organisation for Animal Health since 2007. KHVD is exacerbated in
      aquaculture because of the relatively high host stocking density, and CyHV-3 may
      be concentrated by filter-feeding aquatic organisms. CyHV-3 is taxonomically
      grouped within the family Alloherpesviridae, can be propagated in a number of
      cell lines, and is active at a temperature range of 15 to 28 degrees C. Three
      isolates originating from Japan (KHV-J), USA (KHV-U), and Israel (KHV-I) have
      been sequenced. CyHV-3 has a 295 kb genome with 156 unique open reading frames
      and replicates in the cell nucleus, and mature viral particles are 170 to 200 nm
      in diameter. CyHV-3 can be detected by multiple PCR-based methods and by enzyme
      linked immunosorbent assay. Several modes of immunization have been developed for
      KHVD; however, fish immunized with either vaccine or wild-type virus may become
      carriers for CyHV-3. There is no current treatment for KHVD. 

PMID- 23872861
TI  - Extracellular matrix microenvironment contributes actively to pulmonary fibrosis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the contribution of
      an altered, profibrotic extracellular matrix (ECM) microenvironment to pulmonary
      fibrosis and how it changes cell behaviour and actively drives disease
      progression. RECENT FINDINGS: Idiopathic pulmonary fibrosis is a chronic and
      fatal disease of unknown cause. It is characterized by proliferation and
      accumulation of fibroblasts and myofibroblasts in clusters, termed fibroblastic
      foci, and extensive ECM deposition. Recent evidence from in-vivo and ex-vivo
      experimental studies has highlighted that the abnormal ECM in fibrotic lungs
      alters the behaviour of epithelial and mesenchymal cells. This profibrotic ECM
      microenvironment is characterized by altered biochemical and biomechanical
      properties and stores abundant amount of growth factors. By this, the 'fibrotic
      ECM' can drive progressive fibrogenesis in the lungs without any further
      initiating trigger. These concepts indicate a more complicated dynamic and active
      role of the fibrotic ECM than previously thought and offer many novel therapeutic
      targets. SUMMARY: The fibrotic ECM microenvironment is an active contributor to
      the development and progression of pulmonary fibrosis and a promising therapeutic
      target.

PMID- 23872862
TI  - Photorefractive keratectomy for myopia and myopic astigmatism correction using
      the WaveLight Allegretto Wave Eye-Q excimer laser system.
AB  - To analyze photorefractive keratectomy (PRK) outcomes in myopia and myopic
      astigmatism correction using the WaveLight Allegretto Wave Eye-Q((r)) excimer
      laser system (WaveLight Laser Technologie AG, Erlangen, Germany). 222 eyes of 151
      patients underwent PRK (mean age 33.5 +/- 6.8 years). Pre-operative best
      spectacle-corrected visual acuity (BSCVA) ranged from 0.4 to -0.1 logMAR (mean 
      0.03 +/- 0.06). Mean spherical equivalent (SE) was -3.29 +/- 1.20 D. Efficacy,
      predictability and safety were evaluated. Minimum follow-up was 3 months.
      Accountability at 3 and 6 months was 100 and 54 %, respectively (median follow-up
      5 months, mean 5.2 +/- 2.6 months). At 3 months, mean uncorrected visual acuity
      (UCVA) was -0.02 +/- 0.07 logMAR, BSCVA -0.03 +/- 0.05 logMAR, efficacy index
      0.98 and safety index 1.02. UCVA was >=20/16 in 40.1 %, >=20/20 in 86.5 % and
      >=20/25 in 98.2 %. Mean SE was -0.02 +/- 0.20 D. Residual refractive error was +/
      0.13 D in 81.5 %, +/- 0.25 D in 88.7 % and +/- 0.50 D in 97.7 %. At 6 months,
      outcomes were similar: mean UCVA was -0.02 +/- 0.07 logMAR, BSCVA -0.03 +/- 0.06
      logMAR, efficacy index 1.00 and safety index 1.03. UCVA was >=20/16 in 43.7 %,
      >=20/20 in 86.6 % and >=20/25 in 96.6 %. Mean SE was -0.02 +/- 0.17 D. Residual
      refractive error was +/- 0.13 D in 86.6 %, +/- 0.25 D in 93.3 % and +/- 0.50 D in
      98.3 %. Refractive stability was achieved at 3 months. No patient lost more than
      one line of BSCVA. There were no retreatments. The WaveLight Allegretto Wave Eye
      Q is effective, predictable and safe in low-to-moderate myopia and myopic
      astigmatism PRK correction.

PMID- 23872863
TI  - Experience of a vasopressin receptor antagonist, tolvaptan, under the unique
      indication in Japanese heart failure patients.

PMID- 23872864
TI  - First-in-class angiotensin receptor neprilysin inhibitor in heart failure.
AB  - Neprilysin inhibitors augment the natriuretic peptide system by preventing the
      breakdown of atrial natriuretic peptide and B-type natriuretic peptide. LCZ696,
      an angiotensin receptor neprilysin inhibitor composed of a neprilysin inhibitor
      prodrug and the angiotensin receptor antagonist valsartan, has proven effective
      in hypertension, has shown promise in a pilot trial of heart failure with
      preserved ejection fraction, and is being tested in a large outcomes trial of
      heart failure with reduced ejection fraction. A preserved ejection fraction
      outcomes trial is beginning.

PMID- 23872865
TI  - Surface photovoltage phase spectra for analysing the photogenerated charge
      transfer and photocatalytic activity of ZnFe2O4-TiO2 nanotube arrays.
AB  - The transfer properties of the photogenerated charge carriers in TiO2 nanotube
      arrays (TNAs) and ZnFe2O4 modified TiO2 nanotube arrays (ZFO-TNAs) were
      investigated by surface photovoltage phase spectra. The modification of ZnFe2O4
      on TNAs will lead to a new process of photogeneration of charge carriers. When
      irradiated with UV or visible light, before ZnFe2O4 modification photogenerated
      holes can transfer to the surface of TNAs; while after ZnFe2O4 modification, a
      process of photogenerated electrons transferring to the surface occurred. The
      different detected photogenerated charge transfer processes agree well with the
      photocatalytic reduction of Cr(VI) and the degradation of methyl orange
      experiments, which confirmed that the photogenerated holes transferring to the
      surface of the TNAs or ZFO-TNAs were beneficial for the reactions of
      photocatalytic reduction and electrons transferring to the surface were
      beneficial for photocatalytic degradation.

PMID- 23872866
TI  - Modulation of plasma antioxidant levels, glutathione S-transferase activity and
      DNA damage in smokers following a single portion of broccoli: a pilot study.
AB  - BACKGROUND: Broccoli is a rich source of bioactive compounds (i.e.
      glucosinolates, carotenoids, vitamin C and folate) that may exert an antioxidant
      effect and reduce oxidative damage. The objective of this pilot study was to
      investigate the effect of broccoli consumption on carotenoids, vitamin C and
      folate absorption, glutathione S-transferase (GST) activity, and oxidatively
      induced DNA damage in male smokers. METHODS: Ten healthy subjects consumed a
      single portion of steamed broccoli (250 g) with cooked pasta. Blood was drawn at
      baseline and at 3, 6 and 24 h from consumption. RESULTS: Broccoli significantly
      (P <= 0.01) increased plasma level of vitamin C and folate (+35% and 70%,
      respectively) at 3 h, and beta-carotene (+8%) at 6 h. A modulation of GST
      activity occurred in plasma 6 h after broccoli consumption. A significant (P <=
      0.01) reduction of the levels of H2O2-induced DNA damage (-18%) was observed in
      blood mononuclear cells 24 h after broccoli intake in GSTM1 positive, but not in
      GSTM1 null subjects. CONCLUSION: One portion of broccoli increased plasma
      antioxidant levels, modulated plasma GST activity and improved cell resistance
      against H2O2-induced DNA damage in healthy smokers. These results support the
      importance of consuming fruit and vegetable regularly.

PMID- 23872867
TI  - Quantitative MRI for studying neonatal brain development.
AB  - Quantitative MRI techniques based on morphology and tissue microstructure
      dependent contrast provide a unique window on brain development in the neonatal
      period. The dramatic changes in morphology and MRI contrast that occur during
      this period have the potential to be used to identify normal and abnormal
      developmental trajectories that predict neurodevelopmental outcome in at risk
      populations. Here, we review these technologies focussing on two broad
      categories: gross morphological analysis and tissue microstructure assessment.
      With respect to morphology, we examine the role of image registration and atlas
      based techniques, highlighting the challenges posed by the scale of the
      anatomical changes and the high incidence of radiologically abnormal scans in the
      premature infant population. With respect to microstructure, we examine the
      potential and remaining challenges for using quantitative MRI to dissociate
      processes of cell proliferation, neuronal maturation, and myelination by
      combining different signal contrasts. Recent progress from our group in this area
      is highlighted. 

PMID- 23872868
TI  - Effect of basic fibroblast growth factor on pluripotent marker expression and
      colony forming unit capacity of stem cells isolated from human exfoliated
      deciduous teeth.
AB  - Human dental pulp of exfoliated deciduous teeth contains the population of cells
      that exhibited mesenchymal stem cell (MSC) characters. Though, a cell
      amplification process is indeed required to secure an adequate cell number for
      such a potential employment. Several publications suggested the alteration of
      MSCs upon in vitro culture, for example, the decrease in proliferation and the
      loss of stem cell characters. Here, we investigated an influence of basic
      fibroblast growth factor (bFGF) on stem cells isolated from human exfoliated
      deciduous teeth (SHEDs) with respect to cell proliferation, colony forming unit
      efficiency and stem cell marker expression in both short- and long-term cultures.
      For short-term bFGF treatment, SHEDs were treated with bFGF for 48 h. While, in
      long-term bFGF supplementation, SHEDs were maintained in culture and continuous
      passage upon confluence in medium supplemented with bFGF. Cells at passage (P) 5
      and 10 were employed for characterization. Our results showed that short-term
      bFGF treatment enhanced OCT4, REX1, and NANOG mRNA expression as well as colony
      forming unit ability. The FGFR inhibitor pretreatment was able to attenuate the
      influence of bFGF on pluripotent stem cell marker expression, confirming bFGF
      function. In addition, cells cultured in high passage number had decreased in
      cell proliferation, colony forming unit capacity, and pluripotent stem cell maker
      mRNA expression. However, bFGF supplementation in culture medium enhanced both
      pluripotent stem cell marker expression and colony forming unit capacity in later
      passage, though the effect was not robust. Together, these results indicate that
      high passage number may attenuate pluripotent properties of SHEDs and bFGF
      supplementation could be the beneficial approach to maintain SHEDs' stemness
      properties.

PMID- 23872870
TI  - Controlled synthesis of ultrathin lamellar Eu(2)O(3) nanocrystals: self-assembly
      of 1D nanowires to 2D nanosheets.
AB  - By using 1,5-pentanediol as a capping and structure directing agent, ultrathin
      Eu2O3 nanosheets (<1 nm) have been synthesized and assembled into a layered
      structure. The lateral dimensions of the nanosheets can be tuned by simply
      controlling the reaction time. These layered structures exhibit a strong quantum
      size effect due to the extremely small thickness of the assembled nanosheets. 

PMID- 23872869
TI  - Prolegomena to a neurocomputational architecture for human grammatical encoding
      and decoding.
AB  - This study develops a neurocomputational architecture for grammatical processing
      in language production and language comprehension (grammatical encoding and
      decoding, respectively). It seeks to answer two questions. First, how is online
      syntactic structure formation of the complexity required by natural-language
      grammars possible in a fixed, preexisting neural network without the need for
      online creation of new connections or associations? Second, is it realistic to
      assume that the seemingly disparate instantiations of syntactic structure
      formation in grammatical encoding and grammatical decoding can run on the same
      neural infrastructure? This issue is prompted by accumulating experimental
      evidence for the hypothesis that the mechanisms for grammatical decoding overlap
      with those for grammatical encoding to a considerable extent, thus inviting the
      hypothesis of a single "grammatical coder." The paper answers both questions by
      providing the blueprint for a syntactic structure formation mechanism that is
      entirely based on prewired circuitry (except for referential processing, which
      relies on the rapid learning capacity of the hippocampal complex), and can
      subserve decoding as well as encoding tasks. The model builds on the "Unification
      Space" model of syntactic parsing developed by Vosse and Kempen (Cognition 75:105
      143, 2000; Cognitive Neurodynamics 3:331-346, 2009a). The design includes a
      neurocomputational mechanism for the treatment of an important class of
      grammatical movement phenomena. 

PMID- 23872871
TI  - PLOS Currents: Outbreaks --- For findings that the world just can't wait to see.

PMID- 23872872
TI  - Tumors of the nail unit. A review. Part I: acquired localized longitudinal
      melanonychia and erythronychia.
AB  - The article aims to be a guide to the interpretation of tumors specific to the
      nail, that is, tumors presenting peculiar histological features linked
      specifically to the nail unit. Therefore, the classical epithelial,
      fibroepithelial, and fibrous skin tumors occurring in the nail region are not
      analyzed. The interpretation of nail biopsies requires the identification and
      integration of the 2 main clinical modes of presentation of nail tumors, the
      acquired localized (monodactylous) longitudinal (ALL) band pattern, and the
      "masked" nail tumor. The ALL band pattern often allows the recognition of a nail
      tumor in its early phase of progression, with a limited differential diagnosis.
      The masked nail tumor mimics an inflammatory nail process, as a clinically
      misleading reactive benign lesion, which delays diagnosis with the subsequent
      development of partial nail loss and a locally destructive evolution. ALL band
      pattern appears as a longitudinal band starting at the matrix and extending to
      the tip of the nail plate. The band is usually single, rarely bifid. This
      clinical pattern can divided into 2 presentations. The generic term of ALL
      maculonychia could be proposed to define the macular aspect of the colored band
      of the nail plate. It encompasses 3 syndromes: longitudinal melanonychia,
      longitudinal erythronychia, and longitudinal leukonychia. ALL pachyonychia is a
      rare presentation. Pachyonychia indicates a localized thickening of the nail
      plate specific to the matrical nail tumor. In this group, there is
      differentiation toward cells of the nail matrix. The prototype tumor is the
      onychomatricoma, which present classically with a yellow (xantholeukonychia) band
      pattern. Recently, a new clinical band pattern has been described as longitudinal
      pachymelanonychia with 2 etiologies: pigmented onychomatricoma and onychocytic
      matricoma. The first part of this review delineate, in the first section, the
      distinctive microanatomical features of the nail unit and the second is dedicated
      to the most important pitfalls in pathological diagnosis of nail tumors because
      of nail surgery techniques. In the third section, the histopathology of ALL
      melanonychia and ALL erythronychia is discussed in a detailed description.

PMID- 23872873
TI  - Widespread cutaneous telangiectasias: challenge.

PMID- 23872874
TI  - Poorly differentiated carcinoma arising in the setting of erythema ab igne.
AB  - Erythema ab igne (EAI) is a reticulated, erythematous, or hyperpigmented
      dermatosis that is caused by chronic exposure to infrared radiation. Chronic
      lesions of EAI have significant potential for malignant transformation. We report
      a case of poorly differentiated carcinoma arising within a patch of long-standing
      EAI on the lower extremity of a 92-year-old female. This case highlights the
      importance of recognizing EAI early and counseling patients to avoid further
      exposure to the offending infrared source to reduce the risk of malignant
      transformation. EAI has been associated with several different types of cutaneous
      neoplasms including the Merkel cell carcinoma, squamous cell carcinoma, and
      cutaneous marginal zone lymphoma.

PMID- 23872876
TI  - Diazoxide postconditioning induces mitochondrial protein S-nitrosylation and a
      redox-sensitive mitochondrial phosphorylation/translocation of RISK elements: no
      role for SAFE.
AB  - Postconditioning (PostC) can be obtained either with brief cycles of
      ischemia/reperfusion (I-PostC) or with a direct targeting of mitochondria with
      Diazoxide (pharmacological PostC, P-PostC). I-PostC may induce the activation of
      RISK and SAFE pathways and may favor nitric oxide production with S-Nitrosylation
      of proteins and redox signaling. It is not clear whether Diazoxide can lead to
      similar effects. We compared the effects of I-PostC and P-PostC on (a) kinases of
      RISK- and SAFE pathway, (b) S-Nitrosylation of mitochondrial proteins and (c)
      reduction of death signals (PKCdelta, cleaved caspase-3 and Beclin-1) in
      cytosolic and mitochondrial fractions. Isolated rat hearts underwent (1)
      perfusion without ischemia (Sham), (2) ischemia/reperfusion (30-min ischemia plus
      2-h reperfusion), (3) I-PostC (5 intermittent cycles of 10-s reperfusion and 10-s
      ischemia immediately after the 30-min ischemia), (4) P-PostC (Diazoxide 30 MUM in
      the first of 3-min of reperfusion) or (5) I-PostC + MPG or P-PostC + MPG (MPG, 2
      mercaptopropionylglycine 300 MUM). Using Western blot and biotin switch assay, we
      found that P-PostC induced a redox sensible phosphorylation/translocation of Akt,
      ERK1/2 and GSK3beta into the mitochondria, but not of phospho-STAT3, which was
      translocated into the mitochondria by I-PostC only. Either I-PostC or P-PostC
      increased mitochondrial S-Nitrosylated proteins (e.g., VDAC) and reduced the
      levels of phospho-PKCdelta, cleaved caspase-3 and Beclin-1. Therefore, direct
      targeting of mitochondria with Diazoxide (a) activates the RISK pathway via a
      redox signaling, (b) favors discrete mitochondrial protein S-Nitrosylation,
      including VDAC and (c) decreases signals of death. Intriguingly, phospho-STAT3
      translocation is induced by I-PostC, but not by P-PostC, thus suggesting a redox
      independent mechanism in the SAFE pathway. 

PMID- 23872877
TI  - Should construction workers work harder to improve their health?

PMID- 23872878
TI  - Role of a hippocampal SRC-family kinase-mediated glutamatergic mechanism in drug
      context-induced cocaine seeking.
AB  - Glutamatergic neurotransmission in the dorsal hippocampus (DH) is necessary for
      drug context-induced reinstatement of cocaine-seeking behavior in an animal model
      of drug relapse. Furthermore, in vitro studies suggest that the Src family of
      tyrosine kinases critically regulates glutamatergic cellular functions within the
      DH. Thus, Src-family kinases in the DH may similarly control contextual cocaine
      seeking behavior. To test this hypothesis, rats were trained to lever press for
      un-signaled cocaine infusions in a distinct context followed by extinction
      training in a different context. Cocaine-seeking behavior (non-reinforced active
      lever pressing) was then assessed in the previously cocaine-paired and extinction
      contexts after AP5 (N-methyl-D-aspartate glutamate (NMDA) receptor (NMDAR)
      antagonist; 0.25 or 2.5 MUg/0.5 MUl/hemisphere), PP2 (Src-family kinase
      inhibitor; 6.25 or 62.5 ng/0.5 MUl/hemisphere), Ro25-6981 (NR2B subunit
      containing NMDAR antagonist; 0.2 or 2 MUg/0.5 MUl/hemisphere), or vehicle
      administration into the DH. Administration of AP5, PP2, or Ro25-6981 into the DH
      dose-dependently impaired drug context-induced reinstatement of cocaine-seeking
      behavior relative to vehicle, without altering instrumental behavior in the
      extinction context or food-reinforced instrumental responding and general motor
      activity in control experiments. Cocaine-seeking behavior during the first 20 min
      of the test session in the cocaine-paired context was associated with an increase
      in NR2B subunit activation, and intra-DH PP2 pretreatment disrupted this
      relationship. Together, these findings suggest that Src-family kinase activation,
      NMDAR stimulation, and likely Src-family kinase-mediated NR2B subunit-containing
      NMDAR activation in the DH are necessary for incentive motivational and/or memory
      processes that promote contextual cocaine-seeking behavior. 

PMID- 23872879
TI  - Effects of age on expression of BKca channel in vascular smooth muscle cells from
      mesenteric arteries of spontaneously hypertensive rats.
AB  - Abnormally functioning K(+) channels during aging might contribute to increased
      arterial tone of vascular smooth muscle cells. However, changes in large
      conductance calcium-activated potassium (BKca) channel current density and
      channel protein composition during aging are not fully understood and are
      currently investigated here. Spontaneously hypertensive rats (SHR) and Wistar
      Kyoto (WKY) rats were grouped by age into very young (4-6 weeks), young (16-18
      weeks), and adult (40-42 weeks) rats. BKca current was measured using a whole
      cell patch clamp in vascular smooth muscle cells from rat mesenteric arteries.
      BKca channel and subunits were measured using confocal imaging and real-time
      reverse transcriptase polymerase chain reaction techniques. Systolic and
      diastolic blood pressure increased significantly with age in both SHR and WKY
      rats. The expression of BKca alpha subunits increased in plasma membrane and
      cytoplasm in both SHR and WKY rats during aging, but had a larger increase in the
      cytoplasm in SHR than in WKY rats. BKca current density increased with aging in
      SHR but not in WKY rats. The relative abundance of BKca alpha and beta1 mRNA
      transcripts changed minimally or not at all with aging in both SHR and WKY rats.
      In conclusion, plasma membrane BKca protein increased with aging in both SHR and
      WKY rats. Increases in cytoplasmic BKca protein and in BKca current were greater
      in SHR than WKY rats.

PMID- 23872880
TI  - Antioxidant and hepatoprotective potential of Pouteria campechiana on
      acetaminophen-induced hepatic toxicity in rats.
AB  - Pouteria campechiana (Kunth) Baehni. is used as a remedy for coronary trouble,
      liver disorders, epilepsy, skin disease, and ulcer. Therefore, the present study
      aims to investigate the antioxidant and hepatoprotective effect of polyphenolic
      rich P. campechiana fruit extract against acetaminophen-intoxicated rats. Total
      phenolic and flavonoid contents of egg fruit were estimated followed by the
      determination of antioxidant activities. Treatment with P. campechiana fruit
      extract effectively scavenged the free radicals in a concentration-dependent
      manner within the range of the given concentrations in all antioxidant models.
      The presence of polyphenolic compounds were confirmed by high-performance thin
      layer chromatography (HPTLC). The animals were treated with acetaminophen (250
      mg/kg body weight; p.o.) thrice at the interval of every 5 days after the
      administration of P. campechiana aqueous extract and silymarin (50 mg/kg).
      Acetaminophen treatment was found to trigger an oxidative stress in liver,
      leading to an increase of serum marker enzymes. However, treatment with P.
      campechiana fruit extract significantly reduced the elevated liver marker enzymes
      (aspartate transaminase, alanine transaminase, and alkaline phosphatase) and
      increased the antioxidant enzymes (viz., superoxide dismutase and catalase) and
      glutathione indicating the effect of the extract in restoring the normal
      functional ability of hepatocytes. These results strongly suggest that P.
      campechiana fruit extract has strong antioxidant and significant hepatoprotective
      effect against acetaminophen-induced hepatotoxicity.

PMID- 23872881
TI  - Carnosine and taurine treatments decreased oxidative stress and tissue damage
      induced by D-galactose in rat liver.
AB  - D-galactose (GAL) causes aging-related changes and oxidative stress in the
      organism. We investigated the effect of carnosine (CAR) or taurine (TAU), having
      antioxidant effects, on hepatic injury and oxidative stress in GAL-treated rats.
      Rats received GAL (300 mg/kg; s.c.; 5 days/week) alone or together with CAR (250
      mg/kg/daily; i.p.; 5 days/week) or TAU (2.5 % w/w; in rat chow) for 2 months.
      Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      activities and hepatic malondialdehyde (MDA), protein carbonyl (PC) and
      glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase
      (GSH-0050x), and glutathione transferase (GST) activities were determined.
      Hepatic expressions of B cell lymphoma-2 (Bcl-2), Bax and Ki-67 were evaluated.
      Serum ALT, AST, hepatic MDA, and PC levels were observed to increase in GAL
      treated rats. Hepatic Bax expression, but not Bcl-2, increased, Ki-67 expression
      decreased. GAL treatment caused decreases in GSH levels, SOD and GSH-Px
      activities in the liver. Hepatic mRNA expressions of SOD, but not GSH-Px, also
      diminished. CAR or TAU treatments caused significant decreases in serum ALT and
      AST activities. These treatments decreased apoptosis and increased proliferation
      and ameliorated histopathological findings in the livers of GAL-treated rats.
      Both CAR and TAU reduced MDA and PC levels and elevated GSH levels, SOD and GSH
      Px (non significant in TAU + GAL group) activities. These treatments did not
      alter hepatic mRNA expressions of SOD and GSH-Px enzymes. Our results indicate
      that CAR and TAU restored liver prooxidant status together with histopathological
      amelioration in GAL-induced liver damage.

PMID- 23872882
TI  - The impact of iron content in a diet high in fat, fructose, and salt on metabolic
      state and mineral status of rats.
AB  - The purpose of the study was to assess the influence of dietary iron content on
      lipid and carbohydrate metabolism and on zinc and copper status in rats fed with
      a diet high in fat, fructose, and salt. Wistar rats were fed with diets high in
      fat, fructose, and salt, containing differing amounts of iron, namely, deficit,
      normal, and high levels. After 6 weeks, the animals were weighed and killed. The
      liver, heart, and pancreas were collected, as were blood samples. The total
      cholesterol, triglycerides, fasting glucose, and insulin levels in the serum were
      measured. The iron, zinc, and copper concentrations in tissues and serum were
      determined. It was found that in rats fed with the iron-deficit diet, cholesterol
      and glucose profiles improved. Both deficit and excess iron in the diet decreased
      insulin concentration in rats and disturbed iron, zinc, and copper status. High
      iron level in the diet decreased the relative mass of the pancreas. In
      conclusion, the decrease in serum insulin concentration observed in rats fed with
      the modified diet high in iron was associated with iron and copper status
      disorders, and also, with a relatively diminished pancreas mass. A deficit of
      iron in the diet improved lipid and carbohydrate metabolism in rats.

PMID- 23872883
TI  - Biochemical effects of Solidago virgaurea extract on experimental cardiotoxicity.
AB  - Cardiovascular diseases (CVDs) are the major health problem of advanced as well
      as developing countries of the world. The aim of the present study was to
      investigate the protective effect of the Solidago virgaurea extract on
      isoproterenol-induced cardiotoxicity in rats. The subcutaneous injection of
      isoproterenol (30 mg/kg) into rats twice at an interval of 24 h, for two
      consecutive days, led to a significant increase in serum lactate dehydrogenase,
      creatine phosphokinase, alanine transaminase, aspartate transaminase, and
      angiotensin-converting enzyme activities, total cholesterol, triglycerides, free
      serum fatty acid, cardiac tissue malondialdehyde (MDA), and nitric oxide levels
      and a significant decrease in levels of glutathione and superoxide dismutase in
      cardiac tissue as compared to the normal control group (P < 0.05). Pretreatment
      with S. virgaurea extract for 5 weeks at a dose of 250 mg/kg followed by
      isoproterenol injection significantly prevented the observed alterations.
      Captopril (50 mg/kg/day, given orally), an inhibitor of angiotensin-converting
      enzyme used as a standard cardioprotective drug, was used as a positive control
      in this study. The data of the present study suggest that S. virgaurea extract
      exerts its protective effect by decreasing MDA level and increasing the
      antioxidant status in isoproterenol-treated rats. The study emphasizes the
      beneficial action of S. virgaurea extract as a cardioprotective agent.

PMID- 23872884
TI  - Control of the G-protein cascade dynamics by GDP dissociation inhibitors.
AB  - A network of the Rho family GTPases, which cycle between inactive GDP-bound and
      active GTP-bound states, controls key cellular processes, including proliferation
      and migration. Activating and deactivating GTPase transitions are controlled by
      guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs) and
      GDP dissociation inhibitors (GDIs) that sequester GTPases from the membrane to
      the cytoplasm. Here we show that a cascade of two Rho family GTPases, RhoA and
      Rac1, regulated by RhoGDI1, exhibits distinct modes of the dynamic behavior,
      including abrupt, bistable switches, excitable overshoot transitions and
      oscillations. The RhoGDI1 abundance and signal-induced changes in the RhoGDI1
      affinity for GTPases control these different dynamics, enabling transitions from
      a single stable steady state to bistability, to excitable pulses and to sustained
      oscillations of GTPase activities. These RhoGDI1-controlled dynamic modes of RhoA
      and Rac1 activities form the basis of cell migration behaviors, including
      protrusion-retraction cycles at the leading edge of migrating cells. 

PMID- 23872886
TI  - Binding of aromatic molecules in the fullerene-rich interior of a fullerene
      bilayer vesicle in water.
AB  - Upon dissolution of R5C60(-)K(+) in water, a robust spherical vesicle forms that
      binds aromatic molecules primarily in the interior of the fullerene bilayer, as
      illustrated by the complete quenching of the fluorescence of an aromatic
      fluorescent dye bound in the bilayer. 

PMID- 23872885
TI  - Effectiveness of chamomile (Matricaria recutita L.), MTAD and sodium hypochlorite
      irrigants on smear layer.
AB  - BACKGROUND: Endodontic success depends heavily on effective chemo-mechanical
      debridement of root canals through the use of instruments and irrigating
      solutions. OBJECTIVE: To compare the effectiveness of chamomile hydroalcoholic
      extract, BiopureTM mixture of tetracycline isomer, acid and detergent (MTAD) and
      2.5 % sodium hypochlorite (NaOCl) on removal of the smear layer. STUDY DESIGN:
      Randomised controlled trial. METHODS: Thirty extracted single-rooted, primary
      human teeth were allocated at random into three experimental groups of 10 teeth
      each. For each tooth, the canal was prepared using the step-back technique.
      During instrumentation, 2 ml of the irrigant was used for at least 10 s after
      each file and 10 ml as a final flush for 2 min for chamomile and NaOCL irrigants.
      Whereas for MTAD, an initial rinse with 1.3 % NaOCl for a cumulated period of 20
      min, and use of MTAD as the final rinse for a period of 5 min was followed.
      Longitudinal grooves were made on root segments, then split into two halves with
      a chisel, stored in 2.5 % glutaraldehyde solution and fixed in ethanol series.
      Specimens were examined for the smear layer according to Hulsmann et al. (Int
      Endod J 35:668-679, 2002) criteria using a scanning electron microscope.
      STATISTICS: Kruskal-Wallis and Mann-Whitney U tests were used. RESULTS: The most
      effective result in removal of smear layer occurred with the use of MTAD,
      followed by chamomile extract. The chamomile extract was found to be
      significantly more effective than 2.5 % NaOCl solution which had only minor
      effects. CONCLUSIONS: The efficacy of chamomile to remove the smear layer was
      superior to 2.5 % NaOCl alone, but less effective than MTAD mixture.

PMID- 23872887
TI  - Influence of nutritional status on some toxic and essential elements in the blood
      of women exposed to vehicular pollution in Ile-Ife, Nigeria.
AB  - Blood levels of the elements Cu, Zn, Se, As, Cd, Hg, and Pb have been determined
      in 62 Nigerian women who were occupationally exposed to vehicular pollution.
      Mercury was determined using a direct mercury analyzer, while all the other
      elements were determined by an inductively coupled plasma mass spectrometer
      system. The mean values for all the toxic elements were all within the
      recommended desirable/tolerable limits, except for Se (0.44 MUg/mL, compared with
      <0.2 MUg/mL recommended by the WHO). More than 98% of the subjects had blood
      selenium levels higher than this recommended limit. For As, Hg, and Pb, the
      corresponding figures of subjects with blood levels above the recommended limits
      were 4, 8, and 19.3%, respectively. When the subjects were grouped according to
      their body mass indexes as normal, underweight, overweight, and obese, analysis
      of variance shows that mean blood levels of Cu, As, and, to some extent Hg were
      significantly different in the four nutritional status groups. Blood Hg level
      correlates significantly with blood As in all the groups, except in obese
      subjects. Also, a significant correlation between age and blood Hg was observed
      only in normal subjects and between age and blood Pb only in obese subjects.
      These results suggest that nutritional status could influence both elemental
      levels and the interactions between trace elements in the blood of female
      subjects. Nutrition is therefore a factor to consider in efforts to modify human
      susceptibility to toxic elements.

PMID- 23872888
TI  - Hydrochemical characteristics of mine waters from abandoned mining sites in
      Serbia and their impact on surface water quality.
AB  - Upon completion of exploration and extraction of mineral resources, many mining
      sites have been abandoned without previously putting environmental protection
      measures in place. As a consequence, mine waters originating from such sites are
      discharged freely into surface water. Regional scale analyses were conducted to
      determine the hydrochemical characteristics of mine waters from abandoned sites
      featuring metal (Cu, Pb-Zn, Au, Fe, Sb, Mo, Bi, Hg) deposits, non-metallic
      minerals (coal, Mg, F, B) and uranium. The study included 80 mine water samples
      from 59 abandoned mining sites. Their cation composition was dominated by Ca2+,
      while the most common anions were found to be SO4(2-) and HCO3-. Strong
      correlations were established between the pH level and metal (Fe, Mn, Zn, Cu)
      concentrations in the mine waters. Hierarchical cluster analysis was applied to
      parameters generally indicative of pollution, such as pH, TDS, SO4(2-), Fe total,
      and As total. Following this approach, mine water samples were grouped into three
      main clusters and six subclusters, depending on their potential environmental
      impact. Principal component analysis was used to group together variables that
      share the same variance. The extracted principal components indicated that
      sulfide oxidation and weathering of silicate and carbonate rocks were the primary
      processes, while pH buffering, adsorption and ion exchange were secondary drivers
      of the chemical composition of the analyzed mine waters. Surface waters, which
      received the mine waters, were examined. Analysis showed increases of sulfate and
      metal concentrations and general degradation of surface water quality.

PMID- 23872889
TI  - Polychlorinated biphenyl levels in the blood of Japanese individuals ranging from
      infants to over 80 years of age.
AB  - Individuals' exposure to various persistent organic pollutants (POPs), including
      polychlorinated biphenyls (PCBs), and its adverse health effects have been a
      cause of concern. We measured blood PCB concentrations from samples taken from
      507 Japanese individuals ranging from infants to those over 80 years of age. The
      blood PCB levels increased with age for both male (Spearman's r = 0.69, p <
      0.001) and female (Spearman's r = 0.70, p < 0.001) participants. Adult men and
      nulliparous women showed similar increases with age. However, the PCB levels of
      multiparous women were lower than those of nulliparous women in their thirties (p
      = 0.005), probably because the PCBs were transferred from the mothers to their
      children during pregnancy and lactation. Among infants (<2 years of age), some
      had as high levels of accumulated PCB levels as those in adults >30 years of age.
      In some cases, the PCB levels were over 0.8 ng/g wet weight, similar to levels
      observed in adults over 50 years of age. In the future, it will be necessary to
      do research on the health of the children who are exposed by high concentration
      level of POPs.

PMID- 23872890
TI  - Pb remobilization by bacterially mediated dissolution of pyromorphite Pb5(PO4)3Cl
      in presence of phosphate-solubilizing Pseudomonas putida.
AB  - Remediation of lead (Pb)-contaminated sites with phosphate amendments is one of
      the best studied and cost-effective methods for in situ immobilization. In this
      treatment, a very stable mineral, pyromorphite Pb5(PO4)3Cl, is formed. Several
      studies propose to improve this treatment method with the addition of phosphate
      solubilizing bacteria (PSB). The effect of bacteria on solubilization of
      pyromorphite is unknown. In this study, the effect of the soil microorganisms on
      the stability of pyromorphite Pb5(PO4)3Cl has been investigated in a set of batch
      solution experiments. The mineral was reacted with Pseudomonas putida, a common
      soil microorganism. Dissolution of pyromorphite was enhanced by the presence of
      P. putida, resulting in an elevated Pb concentration in the solution. This
      occurred even when the bacteria were provided with an additional source of
      phosphate in the solution. Pyromorphite has been shown to be a potential source
      of nutrient phosphorus for common soil bacteria. Thus, the use of PSB in
      remediation treatments of Pb contaminated sites may have adverse long-term
      impacts on Pb immobilization. Conscious phosphate management is suggested for
      long-term sustainability of the in situ Pb immobilization by pyromorphite
      formation.

PMID- 23872891
TI  - Temporal and spatial variation of arsenic species in the Dahuofang reservoir in
      northeast China.
AB  - Overlying water, pore water, and sediment samples were collected from the
      Dahuofang reservoir in November 2011 and April 2012, respectively. Total arsenic
      and arsenic species including arsenite, arsenate, monomethylarsonic, and
      dimethylarsinic were analyzed by ICP-MS and HPLC-ICP-MS. The results indicated
      that the environments of the Dahuofang reservoir were in reduced conditions,
      arsenite was the predominant species in pore water and sediments in the
      reservoir. Arsenic concentrations in overlying water were very low in all the
      samples but showed different trend during the different time. In November,
      arsenic concentrations in the reservoir inlet were higher than that in the other
      sites, whereas arsenic showed accumulation from the upstream to downstream of the
      reservoir in samples collected in April. In pore water, arsenic concentrations
      were about 23 and 37 times higher than those in overlying water in November and
      April, respectively, and relatively high levels of arsenite were also detected in
      the pore water. In surface sediments, total arsenic and arsenic species content
      in the reservoir inlet showed the following decreasing order: R1 > R10 > R4. The
      results also showed that moderate ecological risks exist in pore water and
      sediments in the Dahuofang reservoir. 

PMID- 23872893
TI  - Enhancing aerobic digestion potential of municipal waste-activated sludge through
      removal of extracellular polymeric substance.
AB  - A protease-secreting bacteria was used to pretreat municipal sewage sludge to
      enhance aerobic digestion. To enhance the accessibility of the sludge to the
      enzyme, extracellular polymeric substances were removed using citric acid thereby
      removing the flocs in the sludge. The conditions for the bacterial pretreatment
      were optimized using response surface methodology. The results of the bacterial
      pretreatment indicated that the suspended solids reduction was 18% in sludge
      treated with citric acid and 10% in sludge not treated with citric acid whereas
      in raw sludge, suspended solids reduction was 5.3%. Solubilization was 10.9% in
      the sludge with extracellular polymeric substances removed in contrast to that of
      the sludge with extracellular polymeric substances, which was 7.2%, and that of
      the raw sludge, which was just 4.8%. The suspended solids reduction in the
      aerobic reactor containing pretreated sludge was 52.4% whereas that in the
      control reactor was 15.3%. Thus, pretreatment with the protease-secreting
      bacteria after the removal of extracellular polymeric substances is a cost
      effective and environmentally friendly method.

PMID- 23872892
TI  - Characterization of chlordecone-tolerant fungal populations isolated from long
      term polluted tropical volcanic soil in the French West Indies.
AB  - The insecticide chlordecone is a contaminant found in most of the banana
      plantations in the French West Indies. This study aims to search for fungal
      populations able to grow on it. An Andosol heavily contaminated with chlordecone,
      perfused for 1 year in a soil-charcoal system, was used to conduct enrichment
      cultures. A total of 103 fungal strains able to grow on chlordecone-mineral salt
      medium were isolated, purified, and deposited in the MIAE collection
      (Microorganismes d'Interet Agro-Environnemental, UMR Agroecologie, Institut
      National de la Recherche Agronomique, Dijon, France). Internal transcribed spacer
      sequencing revealed that all isolated strains belonged to the Ascomycota phylum
      and gathered in 11 genera: Metacordyceps, Cordyceps, Pochonia, Acremonium,
      Fusarium, Paecilomyces, Ophiocordyceps, Purpureocillium, Bionectria, Penicillium,
      and Aspergillus. Among predominant species, only one isolate, Fusarium oxysporum
      MIAE01197, was able to grow in a liquid culture medium that contained chlordecone
      as sole carbon source. Chlordecone increased F. oxysporum MIAE01197 growth rate,
      attesting for its tolerance to this organochlorine. Moreover, F. oxysporum
      MIAE01197 exhibited a higher EC50 value than the reference strain F. oxysporum
      MIAE00047. This further suggests its adaptation to chlordecone tolerance up to
      29.2 mg l(-1). Gas chromatography-mass spectrometry (GC-MS) analysis revealed
      that 40 % of chlordecone was dissipated in F. oxysporum MIAE01197 suspension
      culture. No chlordecone metabolite was detected by GC-MS. However, weak amount of
      (14)CO2 evolved from (14)C10-chlordecone and (14)C10-metabolites were observed.
      Sorption of (14)C10-chlordecone onto fungal biomass followed a linear
      relationship (r (2) = 0.99) suggesting that it may also account for chlordecone
      dissipation in F. oxysporum MIAE01197 culture.

PMID- 23872894
TI  - Unexpected toxic interactions in the freshwater amphipod Gammarus pulex (L.)
      exposed to binary copper and nickel mixtures.
AB  - To document the toxicity of copper and nickel in binary mixtures, freshwater
      amphipods Gammarus pulex were exposed to the metals given independently or as
      mixtures. Toxicity to Cu alone was relatively high: 96-h LC10 and LC50 were found
      at 91 and 196 MUg L(-1), respectively. Toxicity to Ni alone was very low, with 96
      h LC10 and LC50 of 44,900 and 79,200 MUg L(-1), respectively. Mixture toxicities
      were calculated from single toxicity data using conventional models. Modeled
      toxicity was then compared with the measured toxicity of the binary mixture. Two
      kinds of mixtures were tested. Type I mixtures were designed as combinations of
      Cu and Ni given at the same effect concentrations, when taken independently, to
      identify possible interactions between copper and nickel. In type II mixtures, Cu
      concentrations varied from 0 to 600 MUg L(-1) while the nickel concentration was
      kept constant at 500 MUg L(-1) to mimic conditions of industrial wastewater
      discharges. Ni and Cu showed synergic effects in type I mixtures while type II
      mixtures revealed antagonistic effects. Low doses of Ni reduced Cu toxicity
      towards G. pulex. These results show that even for simple binary mixtures of
      contaminants with known chemistry and toxicity, unexpected interactions between
      the contaminants may occur. This reduces the reliability of conventional
      additivity models. 

PMID- 23872895
TI  - Leachates from solid wastes: chemical and eco(geno)toxicological differences
      between leachates obtained from fresh and stabilized industrial organic sludge.
AB  - The chemical and ecotoxicological characteristics of fresh and stabilized
      industrial organic sludge leachates were compared to obtain information regarding
      how the stabilization process can influence the ecotoxic potential of this
      industrial waste, which could be used for the amendment of degraded soil.
      Physicochemical analysis of the sludge leachates, as well as a battery of
      eco(geno)toxicity tests on bacteria, algae, daphnids, and higher plants
      (including Vicia faba genotoxicity test) and the determination of hydrolytic
      enzyme activity, was performed according to standard methods. The chemical
      comparison of the two types of leachate showed that the samples obtained from
      stabilized sludge had a lower organic content and higher metal content than
      leachates of the fresh sludge. The eco(geno)toxicological results obtained with
      aquatic organisms showed that the stabilized sludge leachate was more toxic than
      the fresh sludge leachate, both originating from the same industrial organic
      sludge sample. Nevertheless, phytotoxicity tests carried out with a reference
      peat soil irrigated with stabilized sludge leachate showed the same toxicity as
      the fresh sludge leachate. In the case of the industrial solid organic sludge
      studied, stabilization through a biodegradation process promoted a higher metal
      mobility/bioavailability/eco(geno)toxicity in the stabilized sludge leachate
      compared to the fresh sludge leachate. 

PMID- 23872896
TI  - Visible light photocatalytic water disinfection and its kinetics using Ag-doped
      titania nanoparticles.
AB  - The UN estimated about five million deaths every year due to water-borne
      diseases, accounting from four billion patients. Keeping in view, the ever
      increasing health issues and to undermine this statistics, a reliable and
      sustainable water-treatment method has been developed using visible light for
      water treatment. titania nanoparticles (NPs) have been synthesized successfully
      by a more applicable method Viz: liquid impregnation (LI) method. The bacterial
      death rate by photocatalysis under visible light was studied by employing a
      typical fluorescent source and was found to follow pseudo first-order reaction
      kinetics. The nanoparticles were characterized using X-ray diffraction (XRD),
      scanning electron microscopy, and energy-dispersive X-ray spectroscopy to deduce
      their size range, surface morphology, and elemental compositions, respectively.
      Among all the prepared grades, 1% Ag-TiO2 was found to be a very effective
      photocatalytic agent against Escherichia coli. The resulted photoinactivated data
      were also evaluated by different empirical kinetic models for bacterial
      inactivation. Hom, Hom-power, Rational, and Selleck models were not able to
      explain the disinfection kinetics but modified-Hom model fitted best with the
      experimentally obtained data by producing a shoulder, log-linear, and a tail
      region.

PMID- 23872897
TI  - Comparative quantification of oxygen release by wetland plants: electrode
      technique and oxygen consumption model.
AB  - Understanding oxygen release by plants is important to the design of constructed
      wetlands for wastewater treatment. Lab-scale systems planted with Phragmites
      australis were studied to evaluate the amount of oxygen release by plants using
      electrode techniques and oxygen consumption model. Oxygen release rate (0.14 g
      O2/m(2)/day) measured using electrode techniques was much lower than that (3.94
      25.20 gO2/m(2)/day) calculated using the oxygen consumption model. The results
      revealed that oxygen release by plants was significantly influenced by the oxygen
      demand for the degradation of pollutants, and the oxygen release rate increased
      with the rising of the concentration of degradable materials in the solution. The
      summary of the methods in qualifying oxygen release by wetland plants
      demonstrated that variations existed among different measuring methods and even
      in the same measuring approach. The results would be helpful for understanding
      the contribution of plants in constructed wetlands toward actual wastewater
      treatment. 

PMID- 23872898
TI  - Microbial biotransformation of aryl sulfanylpentafluorides.
AB  - We report, for the first time, the biotransformation of potential pollutants
      bearing the pentafluorosulfanyl (SF5-) functional group in a fungus and bacteria.
      Cunninghamella elegans transformed p-methoxy phenyl SF5 via demethylation;
      Pseudomonas knackmussii and P. pseudoalcaligenes KF707 transformed amino-,
      hydroxyamino- and diamino- substituted phenyl SF5, forming the N-acetylated
      derivatives as the main product. Cell-free extract of Streptomyces griseus
      transformed 4-amino-3-hydroxy-phenyl SF5 to the N-acetylated derivative in the
      presence of acetyl CoA, confirming that an N-acetyltransferase is responsible for
      the bacterial biotransformations. Approximately 25% of drugs and 30% of
      agrochemicals contain fluorine, and the trifluoromethyl group is a prominent
      feature of many of these since it improves lipophilicity and stability. The
      pentafluorosulfanyl substituent is seen as an improvement on the trifluoromethyl
      group and research efforts are underway to develop synthetic methods to
      incorporate this moiety into biologically active compounds. It is important to
      determine the potential environmental impact of these compounds, including the
      potential biotransformation reactions that may occur when they are exposed to
      microorganisms.

PMID- 23872899
TI  - Immobilization of metal wastes by reaction with H2S in anoxic basins: concept and
      elaboration.
AB  - Metal wastes are produced in large quantities by a number of industries. Their
      disposal in isolated waste deposits is certain to cause many subsequent problems,
      because every material will sooner or later return to the geochemical cycle. The
      sealing of disposal sites usually starts to leak, often within a short time after
      the disposal site has been filled. The contained heavy metals are leached from
      the waste deposit and will contaminate the soil and the groundwater. It is
      evident that storage as metal sulfides in a permanently anoxic environment is the
      only safe way to handle metal wastes. The world's largest anoxic basin, the Black
      Sea, can serve as a georeactor. The metal wastes are sustainably transformed into
      harmless and immobile solids. These are incorporated in the lifeless bottom muds,
      where they are stored for millions of years.

PMID- 23872900
TI  - Zn biomineralization processes and microbial biofilm in a metal-rich stream
      (Naracauli, Sardinia).
AB  - Several decades after the closure of the Ingurtosu mine (SW Sardinia), a variety
      of seasonal Zn biomineralizations occurs. In this work, waters, microbial
      consortia, and seasonal precipitates from the Naracauli stream were sampled to
      investigate chemical composition of stream waters and biominerals, and microbial
      strain identity. Molecular and morphological analysis revealed that activity of
      dominant cyanobacterium Leptolyngbya frigida results in precipitation of Zn
      silicate. The activity of the cyanobacterium was associated to other bacteria and
      many kind of diatoms, such as Halamphora subsalina and Encyonopsis microcephala,
      which are trapped in the process of biomineral growth. In this work, the
      precipitation process is shown to be the result of many different parameters such
      as hydrologic regime, microbial community adaptation, and biological mediation.
      It results in a decrease of dissolved Zn in the stream water, and is a potential
      tool for Zn pollution abatement. 

PMID- 23872901
TI  - Elevated water temperature reduces the acute toxicity of the widely used
      herbicide diuron to a green alga, Pseudokirchneriella subcapitata.
AB  - In the actual environment, temperatures fluctuate drastically through season or
      global warming and are thought to affects risk of pollutants for aquatic biota;
      however, there is no report about the effect of water temperature on toxicity of
      widely used herbicide diuron to fresh water microalgae. The present research
      investigated inhibitory effect of diuron on growth and photosynthetic activity of
      a green alga Pseudokirchneriella subcapitata at five different temperatures (10,
      15, 20, 25, and 30  degrees C) for 144 h of exposure. As a result, effective
      diuron concentrations at which a 50% decrease in algal growth occurred was
      increased with increasing water temperature ranging from 9.2 to 20.1 MUg L(-1)
      for 72 h and 9.4-28.5 MUg L(-1) for 144 h. The photochemical efficiency of
      photosystem II (F v/F m ratio) was significantly reduced at all temperatures by
      diuron exposure at 32 MUg L(-1) after 72 h. Inhibition rates was significantly
      increased with decreased water temperature (P < 0.01). Intracellular H2O2 levels
      as an indicator of oxidative stress were also decreased with increasing
      temperature in both control and diuron treatment groups and were about 2.5 times
      higher in diuron treatment groups than that of controls (P < 0.01). Our results
      suggest water temperatures may affect the toxicokinetics of diuron in freshwater
      and should therefore be considered in environmental risk assessment.

PMID- 23872902
TI  - Pediatric-onset Behcet disease.
AB  - PURPOSE OF REVIEW: Behcet disease has recently been classified as a variable
      vessel vasculitis. This disease is variable not only in the vessel type it
      selects, but also in its clinical presentation. In fact, the heterogeneity of the
      disease has been a drawback in understanding the etiopathogenesis of the disease.
      This review will address the recent developments in our understanding of the
      genetic background and pathogenesis of Behcet disease, as well as the analysis of
      clinical features. RECENT FINDINGS: Recent genome-wide association studies mainly
      confirm the association with HLA-B51 and highlight the association with IL23/IL17
      pathway and IL10, and a molecule that functions in the loading of peptides to HLA
      Class I molecules. Immunological studies also support the role of IL17 in the
      disease pathogenesis. Clinical studies in Behcet disease have provided us with
      clearer definitions of the vascular and central nervous system involvement in
      Behcet disease. An international effort to delineate the characteristics of
      pediatric patients has shown us that we need pediatric classification criteria in
      children with higher sensitivity. As to the treatment of the disease, new
      biological drugs seem to offer promising results in resistant cases. SUMMARY: The
      new pathways defined in the disease will not only help us better understand the
      pathogenesis, but also help us in more targeted therapy. Although pediatric cases
      are being increasingly recognized, the heterogeneity of the disease presents an
      obstacle for studies. Thus, we can reach conclusive results with multicenter
      studies only.

PMID- 23872903
TI  - Update on pathogenesis and treatment of CLE.
AB  - PURPOSE OF REVIEW: Cutaneous Lupus Erythematous (CLE) is an autoimmune disease in
      which patients may present with isolated skin findings or have CLE associated
      with underlying systemic disease. The most significant recent studies on its
      pathogenesis and therapeutic management are reviewed here. RECENT FINDINGS:
      Patients with subacute and Discoid Lupus Erythematous had elevated Interferon
      score, about a third of all cases of SCLE could be attributed to previous drug
      exposure, and smoking may be more closely associated with CLE than Systemic Lupus
      Erythematous (SLE). An underlying genetic defect in some subsets of CLE patients
      may also be shared with SLE. Efficacy of antimalarial therapy is enhanced by
      increasing treatment duration or maintaining higher blood drug concentrations.
      Combination antimalarials that include quinacrine, thalidomide analogs, and
      Mycophenalate Mofetil may also be effective in refractory CLE. SUMMARY: The
      pathogenesis of CLE remains unclear, and is likely multifactorial. Identified
      associations with subsets of CLE suggest future research questions in CLE
      pathogenesis. Subsets of CLE associated with interface dermatitis may share an
      underlying genetic defect in interferon signaling with SLE. The Cutaneous Lupus
      Disease Area and Severity Index is a valuable and widely used tool allowing
      standardized assessment and reporting of cutaneous disease activity and damage.
      More evidence is available to guide treatment of refractory CLE, but larger
      studies are needed. VIDEO ABSTRACT: http://links.lww.com/COR/A4.

PMID- 23872904
TI  - Four-year evolution of a large, state-wide patient-centered medical home
      designation program in Michigan.
AB  - BACKGROUND: The patient-centered medical home (PCMH) has been recognized as a
      strategy to redesign and improve the delivery of primary health care.
      Collaboration between Blue Cross Blue Shield of Michigan (BCBSM) and 39 Physician
      Organizations in Michigan laid the foundation for a state-wide medical home
      program. OBJECTIVE: The objective of the study was to describe a unique
      methodology developed and implemented by BCBSM to designate primary care
      physician practices as medical homes. METHODS: Since 2009, practices were
      designated annually as medical homes on the basis of (1) implementation of PCMH
      related capabilities, and (2) performance on quality-of-care and health resource
      utilization measures. An overall score for each practice was calculated.
      Practices were ranked relative to each other, with the top portion of the
      continuum representing an achievable level of performance. RESULTS: The number of
      practices designated as medical homes more than tripled since the program's
      inception: 302 (1283 physicians) in 2009, 513 (1876 physicians) in 2010, 772
      (2547 physicians) in 2011, and 994 (3028 physicians) in 2012. Designated
      practices reported implementing more than double the PCMH capabilities of
      nondesignated practices, yet all practices increased their number of implemented
      capabilities during the 4 years. DISCUSSION: This program represents the largest
      state-based PCMH program in the United States. Over the 4-year period, 1130
      unique practices have received designation, representing 3469 unique physicians.
      An estimated 1.4 million BCBSM members in Michigan received care from these
      practices. This program will continue to develop, drawing on changes in the
      health system landscape, collaboration with the physician community, and
      knowledge gained from PCMH evaluations.

PMID- 23872905
TI  - Cancer patients' trade-offs among efficacy, toxicity, and out-of-pocket cost in
      the curative and noncurative setting.
AB  - BACKGROUND: When making treatment decisions, cancer patients must make trade-offs
      among efficacy, toxicity, and cost. However, little is known about what patient
      characteristics may influence these trade-offs. METHODS: A total of 400 cancer
      patients reviewed 2 of 3 stylized curative and noncurative scenarios that asked
      them to choose between 2 treatments of varying levels of efficacy, toxicity, and
      cost. Each scenario included 9 choice sets. Demographics, cost concerns,
      numeracy, and optimism were assessed. Within each scenario, we used latent class
      methods to distinguish groups with discrete preferences. We then used regressions
      with group membership probabilities as covariates to identify associations.
      RESULTS: The median age of the patients was 61 years (range, 27-90 y). Of the
      total number of patients included, 25% were enrolled at a community hospital, and
      99% were insured. Three latent classes were identified that demonstrated (1)
      preference for survival, (2) aversion to high cost, and (3) aversion to toxicity.
      Across all scenarios, patients with higher income were more likely to be in the
      class that favored survival. Lower income patients were more likely to be in the
      class that was averse to high cost (P<0.05). Similar associations were found
      between education, employment status, numeracy, cost concerns, and latent class.
      CONCLUSIONS: Even in these stylized scenarios, socioeconomic status predicted the
      treatment choice. Higher income patients may be more likely to focus on survival,
      whereas those of lower socioeconomic status may be more likely to avoid expensive
      treatment, regardless of survival or toxicity. This raises the possibility that
      insurance plans with greater cost-sharing may have the unintended consequence of
      increasing disparities in cancer care.

PMID- 23872906
TI  - Assessing social anxiety in African American youth using the social phobia and
      anxiety inventory for children.

PMID- 23872907
TI  - Voltage mapping for slow-pathway visualization and ablation of atrioventricular
      nodal reentry tachycardia in pediatric and young adult patients.
AB  - Voltage guidance for the ablation of the slow pathway in atrioventricular nodal
      reentry tachycardia (AVNRT) is a dramatic shift from the traditional anatomy
      guided approach within the triangle of Koch. The use of voltage gradient mapping
      has been evaluated in adults as an aid to identification of the slow pathway
      guiding placement of ablation applications. This study aimed to evaluate this
      technique of voltage-guided ablation of AVNRT in pediatric and young adult
      patients, who have a smaller, more compact triangle of Koch. A retrospective
      cohort study evaluated patients 20 years of age or younger with AVNRT who
      underwent voltage mapping. Using NavX, three-dimensional voltage maps of the
      right atrium were created during sinus rhythm, focusing primarily on the triangle
      of Koch. The voltage map gradients were adjusted to uncover a "voltage bridge" of
      lower voltage signals. This bridge was used as a surrogate of the slow pathway to
      guide cryoablation at this site. Of the 31 patients who underwent voltage
      mapping, three were excluded from the study due to inadequate mapping. All the
      patients experienced procedural success. In 86 % of the patients, there was an
      adequate voltage bridge to allow guided ablation. The successful ablation site
      was within the first three lesions for 60 % of the patients. Two patients
      experienced recurrence during a median follow-up period of 14 months. It appears
      that voltage-guided ablation of a voltage bridge in AVNRT can be used effectively
      and safely in the pediatric population. 

PMID- 23872908
TI  - Radiation dose reduction in pediatric cardiac computed tomography: experience
      from a tertiary medical center.
AB  - Cardiac CT angiography (cCTA) has become an established method for the assessment
      of congenital heart disease. However, the potential harmful effects of ionizing
      radiation must be considered, particularly in younger, more radiosensitive
      patients. In this study, we sought to assess the temporal change in radiation
      doses from pediatric cCTA during an 8-year period at a tertiary medical center.
      This retrospective study included all patients <=18 years old who were referred
      to electrocardiography (ECG)-gated cCTA for the assessment of congenital heart
      disease or inflammatory disease (Kawasaki disease) from November 2004 to
      September 2012. During the study period, 95 patients were scanned using 3
      different scanner models-64-slice multidetector CT (64-MDCT) and first- (64-DSCT)
      and second-generation (128-DSCT) dual-source CT-and 3 scan protocols
      retrospective ECG-gated helical scanning (RG), prospective ECG-triggered axial
      scanning (PT), or prospective ECG-triggered high-pitch helical scanning (HPH).
      Effective dose (ED) was calculated with the dose length product method with a
      conversion factor (k) adjusted for age. ED was then compared among scan
      protocols. Image quality was extracted from clinical cCTA reports when available.
      Overall, 94 % of scans were diagnostic (80 % for 64-slice MDCT, 93 % for 64-slice
      DSCT, and 97 % for 128-slice DSCT).With 128-DSCT, median ED (1.0 [range 0.6-2.0]
      mSv) decreased by 85.8 % and 66.8 % compared with 64-MDCT (6.8 [range 2.9-13.6]
      mSv) and 64-DSCT (2.9 [range 0.9-4.1] mSv), respectively. With HPH, median ED
      (0.9 [range 0.6-1.8] mSv) decreased by 59.4 % and 85.4 % compared with PT (2.2
      [range 0.9-3.4] mSv) and RG (6.1 [range 2.5-10.6] mSv). cCTA can now be obtained
      at very low radiation doses in pediatric patients using the latest dual-source CT
      technology in combination with prospective ECG-triggered HPH acquisition. 

PMID- 23872910
TI  - Evidence of extended (>7 years) activity of bevacizumab and metronomic
      cyclophosphamide in a patient with platinum-resistant low-grade serous ovarian
      carcinoma.
AB  - A patient with platinum resistant low-grade serous ovarian carcinoma had an
      objective response to therapy with bevacizumab and evidence of extended activity
      (>7 years). This case report adds to the growing literature regarding the use of
      bevacizumab in low-grade serous ovarian carcinoma.

PMID- 23872909
TI  - Field immobilization for treatment of an unknown illness in a wild chimpanzee
      (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania: findings,
      challenges, and lessons learned.
AB  - Infectious diseases are widely presumed to be one of the greatest threats to ape
      conservation in the wild. Human diseases are of particular concern, and the costs
      and benefits of human presence in protected areas with apes are regularly
      debated. While numerous syndromes with fatal outcomes have recently been
      described, precise identification of pathogens remains difficult. These
      diagnostic difficulties are compounded by the fact that direct veterinary
      intervention on wild apes is quite rare. Here we present the unique case of a
      wild chimpanzee at Gombe National Park that was observed with a severe illness
      and was subsequently examined and treated in the field. Multiple specimens were
      collected and tested with the aim of identifying the pathogen responsible for the
      illness. Our findings represent the first extensive screening of a living wild
      chimpanzee, yet despite our efforts, the cause and source of illness remain
      unknown. Nevertheless, our findings represent valuable baseline data for the ape
      conservation community and for comparison with other recent findings. In
      addition, we present the case here to demonstrate the planning required and
      multiple types of expertise necessary to maximize the amount of data obtained
      from such a rare intervention, and to provide lessons learned for future studies.

PMID- 23872911
TI  - The tricyclic antidepressant amitriptyline is cytotoxic to HTB114 human
      leiomyosarcoma and induces p75(NTR)-dependent apoptosis.
AB  - Nerve growth factor (NGF) receptors, TrKA and p75(NTR), are being investigated in
      cancer therapy. Our previous data show that, in HTB114 uterine leiomyosarcoma
      cells, p75(NTR)-dependent apoptosis is inducible by cytotoxic drugs and can
      suppress nerve growth factor-dependent growth. Although amitriptyline can kill
      cancer cells and bind TrKA/B, its effects on p75-dependent apoptosis are unknown.
      The aim of this paper was to evaluate the antineoplastic potential of
      amitriptyline, and the role of p75(NTR)-dependent apoptosis in the chemoresistant
      uterine HTB114 leiomyosarcoma. Using proliferation assays and fluorescence
      activated cell sorting analysis, we found that amitriptyline caused a marked
      reduction in HTB114 cell viability, associated with the parallel upregulation of
      p75(NTR) expression. This converted the TrKA+-proliferating cells into
      TrKA+/p75(NTR+), leading to downregulation of TrKA-prosurvival signaling (AKT)
      and activation of p75(NTR)-dependent apoptosis (through caspase-3). Overall, we
      provide novel evidence that HTB114 uterine leiomyosarcoma cells are highly
      sensitive to amitriptyline, supporting the role of p75(NTR)-dependent apoptosis
      as a novel cytotoxic mechanism of this drug and of p75(NTR) as an inducible
      stress receptor and a novel target in clinical oncology.

PMID- 23872912
TI  - Mitochondria-targeted antioxidant and glycolysis inhibition: synergistic therapy
      in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related
      deaths worldwide. Mito-carboxy proxyl (Mito-CP), a lipophilic cationic nitroxide,
      accumulates in the mitochondria because of the large negative transmembrane
      potential. Studies have shown that these agents act by disrupting the energy
      producing mechanism, inducing mitochondrial-mediated apoptosis, and also
      enhancing the action of other chemotherapeutic agents in cancer cells. We
      hypothesized that the combination of Mito-CP and glycolysis inhibitor, 2
      deoxyglucose (2-DG), would synergistically inhibit HCC in vitro. HepG2 cells and
      primary hepatocytes were treated with various combinations of Mito-CP and 2-DG.
      Cell cytotoxicity was measured using the methylthiazolyldiphenyl-tetrazolium
      bromide assay and ATP bioluminescence assay. In addition, caspase 3/7 enzymatic
      activity was examined after treatment. Mito-CP and 2-DG induced synergistic
      cytotoxicity in HepG2 cells in a dose-dependent and time-dependent manner,
      whereas primary cells remained viable and unaffected after treatment. The
      intracellular ATP levels of HepG2 cells were suppressed within 6 h of combination
      treatment, whereas primary cells maintained higher levels of ATP. Dose-dependent
      increases in caspase 3/7 activity occurred in HepG2 cells in a time-dependent
      manner, showing the initiation of cell death through the apoptotic pathway. These
      findings indicate that a combination of Mito-CP and 2-DG effectively inhibits HCC
      growth in vitro. The increase in caspase 3/7 activity supports the occurrence of
      2-DG-induced and Mito-CP-induced apoptotic death in HCC. The inability of the
      compounds to induce cytotoxicity or suppress the production of ATP in primary
      hepatocytes provides a selective and synergistic approach for the treatment of
      HCC.

PMID- 23872913
TI  - Silent corticotroph adenoma with adrenal cortical choristoma: a rare but distinct
      morphological entity.
AB  - This report describes a case of pituitary adenoma with interspersed adrenal
      cortical cells. The pituitary cells were confirmed to be corticotrophs with Tpit
      and adrenocorticotropic hormone immunohistochemistry, whereas the adrenal
      cortical cells were verified to be such with steroidogenic factor-1 (SF-1),
      inhibin, calretinin, and Melan A staining. The presence of normal adrenal
      cortical cells in the heterotopic location of the sella fulfills the definition
      of choristoma. The origin of adrenal cortical cells within a pituitary adenoma
      remains unexplained. The important role of SF-1 in both pituitary and adrenal
      cortex may explain a relationship that supports the possibility of an abnormal
      proliferation and differentiation of uncommitted mesenchymal stem cells within
      the sella. However, it remains possible that misplaced adrenal cortical cells
      derived during embryogenesis give rise to this rare but distinct morphological
      entity that can pose a difficult diagnostic dilemma. The approach to differential
      diagnosis is discussed. 

PMID- 23872915
TI  - Oxidant and antioxidant status in children with subacute sclerosing
      panencephalitis.
AB  - We analyzed serum alpha-tocopherol, beta-carotene, retinol, and ascorbic acid
      levels and malondialdehyde and reduced glutathione concentrations on erythrocyte
      and cerebrospinal fluid in 30 patients with subacute sclerosing panencephalitis
      to evaluate oxidant and antioxidant status. Serum alpha-tocopherol, beta
      carotene, retinol, ascorbic acid levels, and erythrocyte and cerebrospinal fluid
      reduced glutathione concentrations were decreased; however, erythrocyte and
      cerebrospinal fluid malondialdehyde levels were increased in the patients.
      Cerebrospinal fluid malondialdehyde levels were different between clinical stages
      of the disease (P < .05). Higher cerebrospinal fluid malondialdehyde level was
      associated with the more severe clinical stage. A positive correlation was found
      between cerebrospinal fluid malondialdehyde level and clinical stages (r = 0.42;
      P < .05) and between erythrocyte malondialdehyde level and clinical stages (r =
      0.40; P < .05). Our findings showed presence of oxidative damage in subacute
      sclerosing panencephalitis and that antioxidants were increased as defense
      mechanisms of the organism against oxidative damage. 

PMID- 23872914
TI  - Metastatic carcinoma to the thyroid gland: a single institution 20-year
      experience and review of the literature.
AB  - The thyroid gland is an uncommon site for metastatic disease but cases have been
      well-documented in the literature, particularly in autopsy series. A
      retrospective review of surgical pathology and autopsy pathology database for
      patients with metastatic carcinoma to the thyroid was performed at the University
      of Massachusetts Medical Center between January 1993 to January 2013. We
      identified a total of 10 patients with metastatic carcinoma to the thyroid; 6
      were in surgical pathology specimens out of a total of 1,295 thyroid carcinoma
      (0.46 %) and 4 were diagnosed at autopsy out of a total of 2,117 (0.19 %) autopsy
      cases during this period. Cases with direct extension of the tumor into the
      thyroid from local primary sites such as larynx, esophagus or soft tissues of the
      neck were excluded. The primary tumors in these cases comprised of four lung
      carcinomas, three colorectal carcinomas, a renal cell carcinoma, a pleural
      malignant mesothelioma, and an unknown primary. Therefore, it is important to
      keep intrathyroidal metastases in the differential diagnosis when evaluating a
      thyroid nodule, particularly in patients with a previous history of malignancy.
      Furthermore, a literature review reveals over 1,400 cases have been previously
      reported, with the most common malignancies from the kidney (34 %), lung (15 %),
      gastrointestinal tract (14 %), and breast (14 %).

PMID- 23872916
TI  - Disseminated encephalomyelitis-like central nervous system neoplasm in childhood.
AB  - A malignant neoplasm in the central nervous system with diffuse white matter
      changes on magnetic resonance imaging (MRI) is rare in children. It could be
      misdiagnosed as acute disseminated encephalomyelitis. This report presents our
      experience based on 4 patients (3 male, 1 female; aged 7-13 years) whose MRI
      showed diffuse lesions in white matter and who were initially diagnosed with
      acute disseminated encephalomyelitis. All of the patients received corticosteroid
      therapy. After brain biopsy, the patients were diagnosed with gliomatosis
      cerebri, primitive neuroectodermal tumor and central nervous system lymphoma. We
      also provide literature reviews and discuss the differentiation of central
      nervous system neoplasm from acute disseminated encephalomyelitis. 

PMID- 23872917
TI  - 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe):
      clinical case with unique confirmatory testing.
AB  - INTRODUCTION: 2C designer drugs have been in use since the 1970s, but new drugs
      continue to develop from substitutions to the base phenethylamine structure. This
      creates new clinical profiles and difficulty with laboratory confirmation. 2-(4
      Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe) is a
      relatively new 2C drug that is more potent than structural 2C analogs; exposure
      reports are rare. Testing for 2C drugs is developing; specific testing for new
      analogs such as 25I-NBOMe is a challenge. These drugs do not reliably trigger a
      positive result on rapid drug immunoassays. Additionally, most facilities with
      confirmatory testing capabilities will not identify 25I-NBOMe; methods for
      detecting 25I-NBOMe in biological samples have not been clearly described nor
      have optimal metabolic targets for detecting 25I-NBOMe ingestion. CASE REPORT: An
      18-year-old female presented following use of 25I-NBOMe. She had an isolated
      brief seizure, tachycardia, hypertension, agitation, and confusion. She improved
      with intravenously administered fluids and benzodiazepines and was discharged 7 h
      postingestion. Urine was analyzed using quantitative LC-MS/MS methodology for 25I
      NBOMe, 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)-methyl]ethanamine
      (25C-NBOMe), and 2-(2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25H
      NBOMe). 25I-NBOMe was found at a concentration of 7.5 ng/mL, and 25H-NBOMe was
      detected as well. Additional testing was pursued to characterize the metabolism
      of 25I-NBOMe; the sample was reanalyzed with UPLC-time-of-flight mass
      spectrometry to identify excreted metabolites. The sample was additionally
      analyzed for the presence of 2,5-dimethoxy-4-iodophenethylamine (2C-I), 4-bromo
      2,5-dimethoxyphenethylamine (2C-B), and 1-(2,5-dimethoxy-4-ethylphenyl)-2
      aminoethane (2C-E). DISCUSSION: This is a report of a patient presenting
      following exposure to 25I-NBOMe, a dangerous member of the evolving 2C drug
      class. The exposure was confirmed in a unique manner that could prove helpful in
      guiding further patient analysis and laboratory studies.

PMID- 23872918
TI  - Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated
      macrophages.
AB  - Macrophages are cellular targets for infection by bacteria and viruses. The fate
      of infected macrophages plays a key role in determining the outcome of the host
      immune response. Apoptotic cell death of macrophages is considered to be a
      protective host defense that eliminates pathogens and infected cells. In this
      study, we investigated the involvement of Notch signaling in regulating apoptosis
      in macrophages treated with tuberculin purified protein derivative (PPD). Murine
      bone marrow-derived macrophages (BMMs) treated with PPD or infected with
      Mycobacterium bovis Bacillus Calmette-Guerin (BCG) induced upregulation of
      Notch1. This upregulation correlated well with the upregulation of the anti
      apoptotic gene mcl-1 both at the transcriptional and translational levels.
      Decreased levels of Notch1 and Mcl-1 were observed in BMM treated with PPD when a
      gamma secretase inhibitor (GSI), which inhibits the processing of Notch
      receptors, was used. Moreover, silencing Notch1 in the macrophage-like cell line
      RAW264.7 decreased Mcl-1 protein expression, suggesting that Notch1 is critical
      for Mcl-1 expression in macrophages. A significant increase in apoptotic cells
      was observed upon treatment of BMM with PPD in the presence of GSI compared to
      the vehicle-control treated cells. Finally, analysis of the mcl-1 promoter in
      humans and mice revealed a conserved potential CSL/RBP-Jkappa binding site. The
      association of Notch1 with the mcl-1 promoter was confirmed by chromatin
      immunoprecipitation. Taken together, these results indicate that Notch1 inhibits
      apoptosis of macrophages stimulated with PPD by directly controlling the mcl-1
      promoter. 

PMID- 23872919
TI  - Impaired NK cell antiviral cytokine response against influenza virus in small-for
      gestational-age neonates.
AB  - The neonates, particularly small-for-gestational-age (SGA) ones, are susceptible
      to various microbial infections. Natural killer (NK) cells are critical
      components of host innate immunity system and the main source of the inflammatory
      cytokines, which provide critical protection during the early phase of viral
      infections before the development of an appropriate adaptive immune response.
      However, little is known about the antiviral effects of NK cells in neonates
      especially the SGA population. Herein, a prospective descriptive study was
      performed to determine the differences of NK cell immunity among adults,
      appropriate-for gestational-age (AGA) and SGA neonates. Adults have much higher
      NK cell number in peripheral blood than that in cord blood from neonates. In
      response to influenza virus stimulation, neonatal NK cells, especially SGA baby
      cells, expressed significantly lower antiviral cytokines including perforin,
      interferon (IFN)-gamma and tumor-necrosis factor (TNF)-alpha responses than adult
      NK cells. In addition, the antiviral cytokine responses of NK cells were
      positively correlated with neonatal birth weight. Our data suggested that the
      depressed antiviral activity and less frequency of NK cells are likely to be
      responsible for the high susceptibility to microbial infection in neonates, at
      least in part. Improving the function of innate immunity may provide a new way to
      defend virus infection. 

PMID- 23872921
TI  - Formation of self-assembled Ag nanoparticles on DNA chains with enhanced
      catalytic activity.
AB  - Self-assembled Ag NPs on DNA chains were synthesized using a simple photochemical
      technique. The size of the individual Ag NPs and their average diameter on the
      DNA chains can be tuned just by controlling the various reaction parameters. The
      average diameter of the self-assembled Ag NPs on DNA chains were varied in the 20
      75 nm range, whereas the average diameters of the individual Ag NPs can be varied
      in the 5-15 nm range. The nominal length of the DNA chains self-assembled by Ag
      NPs can be extended to a few microns. The present process does not need any
      external reducing agent like sodium borohydride or hydrazine or others, and DNA
      itself can act in a dual role: a 'reducing agent' and a 'stabilizing agent' for
      the formation of DNA-Ag NPs colloidal dispersion. The synthesized DNA-Ag NPs were
      well characterized by UV-Vis, EDS, TEM, XRD, XPS, and FT-IR analyses. The self
      assembled Ag NPs on DNA chains were found to have good catalytic activity towards
      the reduction of aromatic nitro compounds. The potentiality of the DNA-Ag NPs as
      catalyst was tested both in solution and after depositing over solid substrate as
      thin films. The synthesized Ag NPs on DNA were found to be extremely stable for a
      period of six months under ambient conditions while kept inside a refrigerator.
      This pronounced catalytic activity of the material might be useful for future
      applications in a variety of organic and inorganic catalysis reactions and in
      SERS-based detection of environmentally important bio-molecules and in sensors. 

PMID- 23872920
TI  - Apoptotic cell administration enhances pancreatic islet engraftment by induction
      of regulatory T cells and tolerogenic dendritic cells.
AB  - Apoptotic cell transfer has been found to be able to facilitate engraftment of
      allograft. However, the underlying mechanisms remain to be fully understood. Here
      we demonstrate that intravenous administration of donor apoptotic splenocytes can
      promote pancreatic islet engraftment by inducing generation of tolerogenic
      dendritic cells (Tol-DCs) and expansion of CD4(+)Foxp3(+) regulatory T cells
      (Tregs). In vivo clearance of either dendritic cells (DCs) or Tregs prevented the
      induction of immune tolerance by apoptotic cell administration. Transient
      elimination of Tregs using anti-CD25, monoclonal antibody (mAb) abrogated the
      generation of Tol-DCs after administration of apoptotic splenocytes.
      Reciprocally, depletion of DCs within CD11c-DTR mice using diphtheria toxin (DT)
      prevented the generation of Tregs in the recipients with administration of
      apoptotic splenocytes. Induction of Tregs by Tol-DCs required direct cell contact
      between the two cell types, and programmed death 1 ligand (PD-L1) played
      important role in the Tregs expansion. Apoptotic cell administration failed to
      induce Tol-DCs in IL-10-deficient and Smad3-deficient mice, suggesting that IL-10
      and transforming growth factor-beta (TGF-beta) are needed to maintain DCs in the
      tolerogenic state. Therefore, we demonstrate that Tol-DCs promote the expansion
      of Tregs via PD-L1 on their surface and reciprocally Tregs facilitate Tol-DCs to
      maintain transplantation tolerance induced by apoptotic cells via secreting IL-10
      and TGF-beta. 

PMID- 23872922
TI  - Prediction of RNA binding proteins comes of age from low resolution to high
      resolution.
AB  - Networks of protein-RNA interactions is likely to be larger than protein-protein
      and protein-DNA interaction networks because RNA transcripts are encoded tens of
      times more than proteins (e.g. only 3% of human genome coded for proteins), have
      diverse function and localization, and are controlled by proteins from birth
      (transcription) to death (degradation). This massive network is evidenced by
      several recent experimental discoveries of large numbers of previously unknown
      RNA-binding proteins (RBPs). Meanwhile, more than 400 non-redundant protein-RNA
      complex structures (at 25% sequence identity or less) have been deposited into
      the protein databank. These sequences and structural resources for RBPs provide
      ample data for the development of computational techniques dedicated to RBP
      prediction, as experimentally determining RNA-binding functions is time-consuming
      and expensive. This review compares traditional machine-learning based approaches
      with emerging template-based methods at several levels of prediction resolution
      ranging from two-state binding/non-binding prediction, to binding residue
      prediction and protein-RNA complex structure prediction. The analysis indicates
      that the two approaches are complementary and their combinations may lead to
      further improvements. 

PMID- 23872923
TI  - Antioxidative effect of aspirin on vascular function of aged ovariectomized rats.
AB  - This study investigated the vascular effects of nonsteroidal anti-inflammatory
      drugs (NSAIDs) in the very late stage of postmenopausal vascular aging and looked
      for a better choice of anti-inflammatory drug for women in reducing the
      cardiovascular risk by decreasing the oxidant status in this term. The rat aorta
      isolated from young and old rats that were treated with either aspirin (10
      mg/kg/day) or indomethacin (INDO, 1 mg/kg/day) within last 10 weeks after 16
      month overiectomy (OVX) follow-up. Endothelium-dependant acetylcholine (Ach,
      0.001-30 MUM) and independent sodium nitroprusside (SNP, 0.0001-3 MUM) relaxant;
      alpha-receptor phenylephrine (PE, 0.001-30 MUM) and voltage-dependant high
      potassium (KCl; 40 mM) contractile responses were assessed. Total oxidant and
      antioxidant status were measured from the serum samples. Aged OVX rat's both
      aortic endothelium and smooth muscle relaxation were significantly less than of
      younger ones, whereas their contractile functions tended to decrease. INDO did
      not treat the Ach, SNP responses, whereas it increased the PE and KCl
      contractility. Aspirin improved the relaxation function and antioxidant capacity
      and decreased the oxidant status. These data demonstrate that even if they are in
      the very late stage of life and menopause, the analgesic choices could restore
      the well established endothelial dysfunction, vascular stiffness, and oxidant
      status.

PMID- 23872924
TI  - Oxidative cross-coupling/cyclization to build polysubstituted pyrroles from
      terminal alkynes and beta-enamino esters.
AB  - A novel silver-mediated highly selective synthesis of polysubstituted pyrroles by
      the C-H/C-H oxidative cross-coupling/cyclization of terminal alkynes with beta
      enamino esters has been developed. This protocol represents a simple, efficient
      and selective way to construct polysubstituted pyrroles in good yields from basic
      chemical materials. 

PMID- 23872925
TI  - Evaluating the prevalence of dementia in hospitalized older adults and effects of
      comorbid dementia on patients' hospital course.
AB  - BACKGROUND AND AIMS: Many older adults with dementia are hospitalized for
      diagnoses other than dementia. We aimed to determine the prevalence of comorbid
      dementia among hospitalized older adults and evaluate its effects on their
      hospital course. METHODS: This retrospective case-control study reviewed the
      hospital records of all adults aged over 60 years admitted to one tertiary
      hospital in China from 2002 to 2012. In total, 34,888 patients meeting the age
      criterion were included. Patients admitted to departments of pediatrics,
      obstetrics and gynecology were not included. Demographic, clinical and outcome
      data from computerized discharge records were collected. Patients diagnosed with
      dementia at discharge by DSM-IV-TR criteria and MMSE scores formed the dementia
      group. All other patients were controls. Illness rating scale, comorbidities,
      mortality at discharge, dementia subtypes and long-term follow-up status for
      dementia patients were analyzed using comparative statistical methods (e.g., one
      way ANOVA with Bonferroni pairwise comparison, Kruskal-Wallis and Mann-Whitney U
      test pairwise comparisons). RESULTS: A total of 918 patients (2.6% prevalence)
      had comorbid dementia, including Alzheimer's disease (39.1%) and vascular
      dementia (39.4%). Neurologic and respiratory system diseases were the most common
      main diagnoses for patients with comorbid dementia, who also had a higher
      percentage of level III or IV severity of main illness compared to controls and
      longer hospital stays (both P < 0.01). Mortality at discharge included 9.80% of
      the dementia group and 8.84% of controls (P = 0.312). CONCLUSION: Comorbid
      dementia has significant effects on hospital course of older adults with various
      main diagnoses, affecting length of stay, severity of illness, and mortality.

PMID- 23872926
TI  - Procalcitonin induced cytotoxicity and apoptosis in mesangial cells: implications
      for septic renal injury.
AB  - OBJECTIVE AND DESIGN: Immuno-neutralization of procalcitonin (ProCT) has been
      shown to ameliorate experimental sepsis as well as the renal complications of
      this disease. Accordingly, we investigated the direct effect of ProCT on
      mesangial cells (MCs). MATERIAL: Primary culture of murine MCs. TREATMENT: ProCT
      (0.5, 1.0, 2.5, 5.0 ng/ml) for 2, 4, 6 h. METHODS: MCs were exposed in vitro to
      ProCT. Expression levels of IL-6, iNOS and TNF-alpha were determined by real time
      RT-PCR, Inflammatory pathways, and a panel of cytokines and chemokines involved
      in the process were investigated by PCR array; apoptosis/viability were evaluated
      in a multiplex assay and actin cytoskeleton alterations were examined by
      immunofluorescence (IF). RESULTS: ProCT caused an early elevation in both IL-6
      and iNOS mRNA (2-4 h), and a later rise (6 h) in TNF-alpha mRNA. ProCT
      upregulated genes of proinflammatory pathways 5- to 24-fold compared to control.
      IF images revealed disruption of the actin cytoskeleton and retraction of cell
      bodies with loss of typical stellate or spindle shape phenotype. ProCT decreased
      MCs viability by 36 % compared to control cells and induced significant
      apoptosis. CONCLUSIONS: ProCT has direct cytotoxic properties and may play a role
      in septic acute kidney injury that is independent of endotoxemia or hemodynamic
      alterations.

PMID- 23872927
TI  - Macrophages: plastic solutions to environmental heterogeneity.
AB  - INTRODUCTION: Macrophages are among the oldest cell types in the animal kingdom,
      and they have a long evolutionary history and experience various evolutionary
      pressures. It was clear from the earliest studies that variations exist in
      macrophage populations. Macrophages are known to adapt to their microenvironment.
      Although the paradigm for macrophage plasticity is their flexible program driven
      by environmental signals, the most common working hypothesis is that of a
      dichotomy between two major macrophage phenotypes, M1 and M2. METHODS: A PubMed
      and Web of Science databases search was performed providing evidences that
      numerous authors have expanded the concept of plasticity and conducted
      experimental studies focusing on the complex program of phenotypes. RESULTS AND
      CONCLUSIONS: This review evaluated a number of issues relating to macrophage
      plasticity, environmental heterogeneity and the potential for changes to be
      reversal or non reversal in an ecological context. The ecological principles of
      phenotypic plasticity which can assist in evaluating and interpreting macrophage
      experimental data are discussed as well.

PMID- 23872930
TI  - Can't take the heat: high temperature depletes bacterial endosymbionts of ants.
AB  - Members of the ant tribe Camponotini have coevolved with Blochmannia, an obligate
      intracellular bacterial mutualist. This endosymbiont lives within host
      bacteriocyte cells that line the ant midgut, undergoes maternal transmission from
      host queens to offspring, and contributes to host nutrition via nitrogen
      recycling and nutrient biosynthesis. While elevated temperature has been shown to
      disrupt obligate bacterial mutualists of some insects, its impact on the ant
      Blochmannia partnership is less clear. Here, we test the effect of heat on the
      density of Blochmannia in two related Camponotus species in the lab.
      Transcriptionally active Blochmannia were quantified using RT-qPCR as the ratio
      of Blochmannia 16S rRNA to ant host elongation factor 1-alpha transcripts. Our
      results showed that 4 weeks of heat treatment depleted active Blochmannia by >99
      % in minor workers and unmated queens. However, complete elimination of
      Blochmannia transcripts rarely occurred, even after 16 weeks of heat treatment.
      Possible mechanisms of observed thermal sensitivity may include extreme AT
      richness and related features of Blochmannia genomes, as well as host stress
      responses. Broadly, the observed depletion of an essential microbial mutualist in
      heat-treated ants is analogous to the loss of zooanthellae during coral
      bleaching. While the ecological relevance of Blochmannia's thermal sensitivity is
      uncertain, our results argue that symbiont dynamics should be part of models
      predicting how ants and other animals will respond and adapt to a warming
      climate.

PMID- 23872928
TI  - A pilot study of urinary fibroblast growth factor-2 and epithelial growth factor
      as potential biomarkers of acute kidney injury in critically ill children.
AB  - BACKGROUND: Acute kidney injury (AKI) increases the morbidity of critically ill
      children. Thus, it is necessary to identify better renal biomarkers to follow the
      outcome of these patients. This prospective case-control study explored the
      clinical value of a urinary biomarker profile comprised of neutrophil gelatinase
      lipocalin (uNGAL), fibroblast growth factor-2 (uFGF-2), and epidermal growth
      factor (uEGF) to follow these patients. METHODS: Urine samples were collected
      from 21 healthy children, and 39 critically ill children (mean age 7.5 years +/-
      6.97 SD) admitted to a pediatric intensive care unit with sepsis or requiring
      extra corporeal membrane oxygenation (ECMO). uNGAL, uFGF-2, and uEGF levels were
      measured using ELISA kits during the first 24 h of admission to PICU, at peak of
      illness, and upon resolution of the critical illness. RESULTS: On admission, the
      uNGAL and uFGF-2 levels were increased, and the uEGF levels were decreased, in
      critically ill children with AKI (n = 19) compared to those without AKI (n = 20),
      and healthy controls. A biomarker score using the combined cut-off values of
      uNGAL, uFGF-2, and uEGF (AUC = 0.90) showed the highest specificity to identify
      children with AKI, relative to each biomarker alone. uNGAL and uFGF-2 on
      admission showed high sensitivity and specificity to predict mortality (AUC =
      0.82). CONCLUSIONS: The biomarker profile comprised of uNGAL, uFGF-2, and uEGF
      increased the specificity to detect AKI in critically ill children, when compared
      to each biomarker used alone. uNGAL and uFGF-2 may also predict the risk of
      death. Further validation of these findings in a large sample size is warranted.

PMID- 23872929
TI  - Acute kidney injury and its association with in-hospital mortality among children
      with acute infections.
AB  - BACKGROUND: We investigated prevalence of acute kidney injury (AKI) at
      hospitalization and its association with in-hospital mortality among Ugandan
      children hospitalized with common acute infections, and predictors of mortality
      among AKI children. METHODS: We enrolled 2,055 children hospitalized with primary
      diagnoses of acute gastroenteritis, malaria, or pneumonia. Serum creatinine,
      albumin, electrolytes, hemoglobin, and urine protein were obtained on admission.
      Participants were assessed for AKI based on serum creatinine levels. Demographic
      and clinical data were obtained using a primary care provider survey and medical
      chart review. Logistic regression was used to determine predictors of in-hospital
      mortality. RESULTS: A total of 278 (13.5%) of children had AKI on admission; for
      76.2%, AKI was stage 2 (98/278) or stage 3 (114/278) defined as serum creatinine
      >2- or 3-fold above normal upper limit for age, respectively. AKI prevalence was
      particularly high in gastroenteritis (28.6%) and underweight children (20.7%).
      Twenty-five percent of children with AKI died during hospitalization, compared to
      9.9% with no AKI (adjusted odds ratio (aOR) 3.5 (95% CI, 2.2-5.5)). In-hospital
      mortality risk did not differ by AKI stage. Predictors of in-hospital mortality
      among AKI children included primary diagnosis of pneumonia, aOR 4.5 (95% CI, 1.8
      11.2); proteinuria, aOR = 2.1 (95% CI, 1.0-4.9) and positive human
      immunodeficiency virus (HIV) status, aOR 5.0 (95% CI, 2.0-12.9). CONCLUSIONS:
      Among children hospitalized with gastroenteritis, malaria, or pneumonia, AKI at
      admission was common and associated with high in-hospital mortality.

PMID- 23872931
TI  - Notable catalytic activity of oxygen-vacancy-rich WO(2.72) nanorod bundles as
      counter electrodes for dye-sensitized solar cells.
AB  - For the first time, nonstoichiometric WO2.72 was used as a counter electrode (CE)
      in dye-sensitized solar cells (DSSCs). Oxygen-vacancy-rich WO2.72 nanorod bundles
      with notable catalytic activity for triiodide and thiolate reduction were
      prepared in this study. The photovoltaic parameters of dye-sensitized solar cells
      (DSSCs) with WO2.72 nanorod bundles as CEs are superior compared with those of
      the WO3-based cells, and nearly the same as those of the precious metal Pt-based
      cells. In a non-corrosive organic redox couple, the performance of WO2.72 CEs is
      better than that of Pt and WO3 CEs in DSSCs. 

PMID- 23872932
TI  - A burning issue: preventing patient fires in the operating room.

PMID- 23872933
TI  - Flammability of surgical drapes and materials in varying concentrations of
      oxygen.
AB  - BACKGROUND: Over 600 operating room fires occur annually although many cases go
      unreported. Over 81% of operating room fires involve surgical drapes, yet limited
      data exist on the differing degrees of flammability of drapes and other surgical
      fuel sources in varying oxygen concentrations. The purpose of this study is to
      assess the flammability characteristics of fuels in the operating room under
      varying oxygen concentrations. METHODS: Five fuel sources were analyzed in three
      levels of oxygen: 21%, 50%, and 100%. Three test samples of each material were
      burned in a manner similar to that established by the Consumer Product Safety
      Commission. Time to sample ignition and time to complete burn were measured with
      video analysis. RESULTS: The median [minimum, maximum] ignition time in 21%
      oxygen was 0.9 s [0.3, 1.9], in 50% oxygen 0.4 s [0.1, 1.2], and in 100% oxygen
      0.2 s [0.0, 0.4]. The median burn time in 21% oxygen was 20.4 s [7.8, 33.5], in
      50% oxygen 3.1 s [1.4, 8.1], and in 100% oxygen 1.7 s [0.6, 2.7]. Time to ignite
      and total burn times decreased as oxygen concentration increased (P < 0.001).
      Flammability characteristics differed by material and oxygen concentration.
      Utility drapes and surgical gowns did not support combustion in room air, whereas
      other materials quickly ignited. Flash fires were detected on woven cotton
      materials in oxygen-enriched environments. CONCLUSIONS: Operating room personnel
      should be aware that common materials in the operating room support rapid
      combustion in oxygen-enriched environments. The risk of ignition and speed of
      fire propagation increase as oxygen exposure increases. Advances in material
      science may reduce perioperative fire risk.

PMID- 23872934
TI  - Laryngeal papillomatosis.

PMID- 23872935
TI  - A new method to determine rate-dependent material parameters of corneal
      extracellular matrix.
AB  - The cornea protects internal ocular contents against external insults while
      refracting and transmitting the incoming light onto the lens. The biomechanical
      properties of the cornea are largely governed by the composition and structure of
      the stromal layer which is an extracellular matrix composed of collagen fibrils
      embedded in a hydrated soft matrix. The mechanical behavior of the corneal stroma
      has commonly been characterized using uniaxial tensile tests and inflation
      experiments. In the present study, unconfined compression experiments were used
      to investigate the influence of loading rates on compressive behavior of nineteen
      porcine corneal specimens. The experiments were performed at ramp displacement
      rates 0.15 MUm/s (eight samples), 0.5 MUm/s (six samples), and 1.0 MUm/s (five
      samples). For all tests, a maximum compressive strain of 50% (five strain
      increments of 4% followed by three strain increments of 10%) was selected. The
      experimental data was analyzed by a transversely isotropic biphasic model and
      material parameters, i.e., the in-plane Young's modulus, the out-of-plane Young's
      modulus, and the permeability coefficient were calculated. It was observed that
      while the permeability coefficient decreased exponentially with increasing
      compressive strain, the in-plane and out-of-plane Young's moduli increased
      exponentially with increasing strain. Furthermore, it was found that the
      equilibrium stress was almost rate independent. 

PMID- 23872936
TI  - Impact of ventilation frequency and parenchymal stiffness on flow and pressure
      distribution in a canine lung model.
AB  - To determine the impact of ventilation frequency, lung volume, and parenchymal
      stiffness on ventilation distribution, we developed an anatomically-based
      computational model of the canine lung. Each lobe of the model consists of an
      asymmetric branching airway network subtended by terminal, viscoelastic acinar
      units. The model allows for empiric dependencies of airway segment dimensions and
      parenchymal stiffness on transpulmonary pressure. We simulated the effects of
      lung volume and parenchymal recoil on global lung impedance and ventilation
      distribution from 0.1 to 100 Hz, with mean transpulmonary pressures from 5 to 25
      cm H2O. With increasing lung volume, the distribution of acinar flows narrowed
      and became more synchronous for frequencies below resonance. At higher
      frequencies, large variations in acinar flow were observed. Maximum acinar flow
      occurred at first antiresonance frequency, where lung impedance achieved a local
      maximum. The distribution of acinar pressures became very heterogeneous and
      amplified relative to tracheal pressure at the resonant frequency. These data
      demonstrate the important interaction between frequency and lung tissue stiffness
      on the distribution of acinar flows and pressures. These simulations provide
      useful information for the optimization of frequency, lung volume, and mean
      airway pressure during conventional ventilation or high frequency oscillation
      (HFOV). Moreover our model indicates that an optimal HFOV bandwidth exists
      between the resonant and antiresonant frequencies, for which interregional gas
      mixing is maximized.

PMID- 23872937
TI  - Effect of a ball skill intervention on children's ball skills and cognitive
      functions.
AB  - PURPOSE: This study examined the effect of a 16-wk ball skill intervention on the
      ball skills, executive functioning (in terms of problem solving and cognitive
      flexibility), and in how far improved executive functioning leads to improved
      reading and mathematics performance of children with learning disorders. METHODS:
      Ninety-one children with learning disorders (age 7-11 yr old) were recruited from
      six classes in a Dutch special-needs primary school. The six classes were
      assigned randomly either to the intervention or to the control group. The control
      group received the school's regular physical education lessons. In the
      intervention group, ball skills were practiced in relative static, simple
      settings as well as in more dynamic and cognitive demanding settings. Both groups
      received two 40-min lessons per week. Children's scores on the Test of Gross
      Motor Development-2 (ball skills), Tower of London (problem solving), Trail
      Making Test (cognitive flexibility), Dutch Analysis of Individual Word Forms
      (reading), and the Dutch World in Numbers test (mathematics) at pretest,
      posttest, and retention test were used to examine intervention effects. RESULTS:
      The results showed that the intervention group significantly improved their ball
      skills, whereas the control group did not. No intervention effects were found on
      the cognitive parameters. However, within the intervention group, a positive
      relationship (r = 0.41, P = 0.007) was found between the change in ball skill
      performance and the change in problem solving: the larger children's improvement
      in ball skills, the larger their improvement in problem solving. CONCLUSIONS: The
      present ball skill intervention is an effective instrument to improve the ball
      skills of children with learning disorders. Further research is needed to examine
      the effect of the ball skill intervention on the cognitive parameters in this
      population.

PMID- 23872938
TI  - Intravenous iron supplementation in distance runners with low or suboptimal
      ferritin.
AB  - PURPOSE: Iron deficiency is prevalent in distance runners and may impair
      endurance performance. The current practice of oral supplementation is slow and
      often not well tolerated. The aim of this study was to assess the efficacy of
      intravenous (IV) iron supplementation (ferric carboxymaltose) compared with oral
      supplementation (ferrous sulfate) on iron status, hemoglobin mass (Hbmass), and
      physiological indices of running performance in distance runners. METHODS: Twenty
      seven highly trained distance runners with low (LOW) (ferritin <35 MUg.L(-1) and
      transferrin saturation <20%, or ferritin <15 MUg.L(-1)) or suboptimal (SUB) iron
      status (ferritin <65 MUg.L(-1)) were supplemented with either IV iron
      (Ferinject(r)) or oral (ORAL) supplements (Ferrogradumet) for 6 wk. Iron status
      and Hbmass were assessed before supplementation and at 1, 2, 4, 6, and 8 wk in
      the four groups (IV LOW, IV SUB, ORAL LOW, and ORAL SUB). In addition, athletes
      completed a treadmill running test for running economy, lactate threshold, and
      VO2max before and after supplementation. RESULTS: Both forms of supplementation
      substantially increased ferritin levels in all four groups. IV supplementation
      resulted in higher ferritin in both IV groups compared with both ORAL groups from
      week 1 onward. Hemoglobin concentration did not change substantially in any
      group. Hbmass increased in IV LOW (mean = +4.9%, 90% confidence interval [CI] =
      1.1%-8.9%) and was accompanied by an increase in VO2max (mean = +3.3%, 90% CI =
      0.4%-6.3%) and run time to exhaustion (mean = +9.3%, 90% CI = 0.9%-18.3%.
      CONCLUSIONS: IV supplementation can effectively increase iron stores in iron
      deficient runners within 6 wk and, if Hbmass is compromised, may enhance
      endurance capacity by facilitating erythropoiesis. Hbmass appears a more
      sensitive tool for measuring changes in whole body hemoglobin than hemoglobin
      concentration and may be useful in the diagnosis and follow-up for iron
      deficiency.

PMID- 23872939
TI  - One bout of exercise alters free-living postprandial glycemia in type 2 diabetes.
AB  - PURPOSE: Elevated postprandial glycemic (PPG) excursions are significant risk
      factors for cardiovascular disease in type 2 diabetes patients. In this study, we
      tested if and for how many meals a single bout of exercise would reduce PPG
      responses to subsequent meals in type 2 diabetes (T2D) patients using a
      continuous glucose monitor system (CGMS). METHODS: We recruited nine sedentary
      (<30 min.wk(-1) of exercise) individuals with T2D (mean +/- SD; body mass index =
      36.0 +/- 1.1 kg.m(-2), age = 60.3 +/- 1.0 yr, HbA1c = 6.3% +/- 0.2%). The
      subjects consumed a eucaloric diet (51% carbohydrate, 31% fat, and 18% protein)
      consisting of three meals, identical in composition, for a 2-d period while
      wearing a continuous glucose monitor system in two different conditions (exercise
      [EX], one 60-min bout at 60%-75% of heart rate reserve performed before
      breakfast), vs a sedentary [SED] condition). We quantified 24-h average glucose,
      PPG area under the curve (AUC; 4-h glucose AUC after meals), and PPG-2 h (2 h
      postprandial glucose). RESULTS: EX significantly reduced average [glucose] during
      the first 24-h period (P = 0.03). EX caused a reduction in PPG-AUC (P = 0.02) for
      all of the meals during the 2 d (main effect between conditions). A comparison
      between the EX and the SED conditions at each meal revealed that EX reduced PPG
      AUC after the second meal of day 1 (lunch) (P = 0.04). PPG-2 h was not
      significantly different between EX and SED. CONCLUSIONS: Although a single EX
      bout does lower 24-h average [glucose], it only significantly lowered PPG-AUC at
      the second meal after the bout, suggesting that daily exercise may be needed to
      most effectively improve PPG at the advent of exercise training in T2D patients.

PMID- 23872940
TI  - Gastric metastases from testicular cancer: case report and review of literature.

PMID- 23872941
TI  - Incidence and behavioral correlates of epileptiform abnormalities in autism
      spectrum disorders.
AB  - Autism spectrum disorders (ASD) are associated with an increased incidence of
      epilepsy and of epileptiform discharges on electroencephalograms. It is unknown
      whether epileptiform discharges correlate with symptoms of ASD. We completed a
      retrospective chart review of 101 patients with ASD who had overnight
      electroencephalograms. We looked for a relationship between epileptiform
      abnormalities and diagnosis, history of regression, communication skills, and
      other features associated with ASD. There was a higher incidence of epileptiform
      activity in children with stereotypies and aggressive behavior. The incidence of
      epileptiform abnormalities was significantly lower in Asperger's compared with
      more severe forms of autism. Results suggest that increasing severity of autistic
      symptoms may be associated with higher likelihood of epileptiform abnormalities.
      Whether treatment alters outcome is unknown. 

PMID- 23872942
TI  - Smiling response, stranger anxiety, and autistic disorder.

PMID- 23872943
TI  - Viral evolution: Variation in the gut virome.

PMID- 23872944
TI  - Viral infection: Propelling vaccinia virus to the neighbours.

PMID- 23872945
TI  - Mild yet phase-selective preparation of TiO2 nanoparticles from ionic liquids--a
      critical study.
AB  - The phase selective synthesis of nanocrystalline TiO2, titania, in ionic liquids
      (ILs) is explored. The influence not only of the IL but also of the Ti-precursor,
      pH, and temperature is investigated. Sonochemical synthesis, microwave synthesis
      and conventional heating are compared. In the case of Ti(O(i)Pr)4 (O(i)Pr =
      isopropyl) as the Ti-source the ILs [C4mim][Tf2N] (1-butyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)amide), [C3mimOH][Tf2N] (1-(3-hydroxypropyl)-3
      methylimidazolium bis(trifluoromethanesulfonyl)amide), [C4Py][Tf2N]
      (butylpyridinium bis(trifluoromethanesulfonyl)amide), [N1888][Tf2N]
      (methyltrioctylammonium bis(trifluoromethanesulfonyl)amide), and [P66614][Tf2N]
      (tetradecyltrihexyl phosphonium bis(trifluoromethanesulfonyl)amide) led at
      ambient temperature to TiO2 in the form of anatase. The morphology of nano
      anatase is controlled by the IL cation. Anatase nanospheres with a crystal size
      below 10 nm are obtained in [C3mimOH][Tf2N], [P66614][Tf2N] and [C4Py][Tf2N],
      whilst nanorods with a length and diameter of ~10 to 20 and 5 nm are formed in
      [N1888][Tf2N] and spindle-shaped particles with an average length of 10-25 nm are
      formed in [C4mim][Tf2N]. Calcination at temperatures above 730  degrees C leads
      to rutile. When using TiCl4 as the Ti-precursor an anatase-rutile mixture forms
      under ambient conditions. Pure rutile can be obtained under ambient conditions in
      the presence of an appropriate volume of aqueous HCl. At moderate to high pH
      values pure anatase can be obtained even from TiCl4. The photocatalytic activity
      of the obtained TiO2 materials has been assessed by the photodegradation of an
      aqueous methyl orange solution under UV light. The results indicate that the
      photocatalytic activity of anatase-brookite mixtures obtained in [C4mim][Tf2N],
      [N1888][Tf2N] and [P66614][Tf2N] is higher than that of pure anatase which is
      formed in [C3mimOH][Tf2N] and [C4Py][Tf2N] and competitive with commercially
      available catalysts. 

PMID- 23872946
TI  - DPY30 regulates pathways in cellular senescence through ID protein expression.
AB  - Cellular senescence is an intrinsic defense mechanism to various cellular
      stresses: while still metabolically active, senescent cells stop dividing and
      enter a proliferation arrest. Here, we identify DPY30, a member of all mammalian
      histone H3K4 histone methyltransferases (HMTases), as a key regulator of the
      proliferation potential of human primary cells. Following depletion of DPY30,
      cells show a severe proliferation defect and display a senescent phenotype,
      including a flattened and enlarged morphology, elevated level of reactive oxygen
      species (ROS), increased SA-beta-galactosidase activity, and formation of
      senescence-associated heterochromatin foci (SAHFs). While DPY30 depletion leads
      to a reduced level of H3K4me3-marked active chromatin, we observed a concomitant
      activation of CDK inhibitors, including p16INK4a, independent of H3K4me3. ChIP
      experiments show that key regulators of cell-cycle progression, including ID
      proteins, are under direct control of DPY30. Because ID proteins are negative
      regulators of the transcription factors ETS1/2, depletion of DPY30 leads to the
      transcriptional activation of p16INK4a by ETS1/2 and thus to a senescent-like
      phenotype. Ectoptic re-introduction of ID protein expression can partially rescue
      the senescence-like phenotype induced by DPY30 depletion. Thus, our data indicate
      that DPY30 controls proliferation by regulating ID proteins expression, which in
      turn lead to senescence bypass. 

PMID- 23872948
TI  - Inhaled corticosteroids and risk of recurrent pneumonia: a population-based,
      nested case-control study.
AB  - BACKGROUND: Studies have suggested an increased risk of pneumonia with inhaled
      corticosteroid (ICS) use, although this association is inconsistent. We evaluated
      the risk of recurrent pneumonia associated with ICS use in a high-risk population
      of individuals who survived an episode of pneumonia. METHODS: Clinical and 5-year
      follow-up data were collected on all adults aged >= 65 years with pneumonia over
      a period of 2 years. Using a nested case-control design, first cases (patients
      with recurrent pneumonia >= 30 days after initial episode) and then controls
      (free of pneumonia and matched on age, sex, and chronic obstructive pulmonary
      disease [COPD]) were identified. ICS use was classified as never, past (remote,
      only before initial pneumonia), or current. Our primary outcome measure was
      recurrent pneumonia assessed using conditional multivariate logistic regression
      after adjustment of demographics and clinical data. RESULTS: During 5 years of
      follow-up, 653 recurrent pneumonia cases were matched with 6244 controls; mean
      age was 79 (SD, 8) years, 3577 (52%) were male, 2652 (38%) had COPD, and 2294
      (33%) ever used ICS. Overall, 123 of 870 (14%) current ICS users had recurrent
      pneumonia compared to 395 of 4603 (9%) never-users (adjusted odds ratio, 1.90;
      95% confidence interval, 1.45-2.50; P < .001; number need to harm = 20).
      Conversely, there was no association between past (remote) use of ICS and
      pneumonia: 9% of past users versus 9% never-users (P = .36). CONCLUSIONS: ICS use
      was associated with a 90% relative increase in the risk of recurrent pneumonia
      among high-risk pneumonia survivors. This should be considered when prescribing
      ICS and when deciding which patients might need more intensive follow-up.

PMID- 23872947
TI  - SAMHD1-dependent retroviral control and escape in mice.
AB  - SAMHD1 is a host restriction factor for human immunodeficiency virus 1 (HIV-1) in
      cultured human cells. SAMHD1 mutations cause autoimmune Aicardi-Goutieres
      syndrome and are found in cancers including chronic lymphocytic leukaemia. SAMHD1
      is a triphosphohydrolase that depletes the cellular pool of deoxynucleoside
      triphosphates, thereby preventing reverse transcription of retroviral genomes.
      However, in vivo evidence for SAMHD1's antiviral activity has been lacking. We
      generated Samhd1 null mice that do not develop autoimmune disease despite
      displaying a type I interferon signature in spleen, macrophages and fibroblasts.
      Samhd1(-/-) cells have elevated deoxynucleoside triphosphate (dNTP) levels but,
      surprisingly, SAMHD1 deficiency did not lead to increased infection with VSV-G
      pseudotyped HIV-1 vectors. The lack of restriction is likely attributable to the
      fact that dNTP concentrations in SAMHD1-sufficient mouse cells are higher than
      the KM of HIV-1 reverse transcriptase (RT). Consistent with this notion, an HIV-1
      vector mutant bearing an RT with lower affinity for dNTPs was sensitive to SAMHD1
      dependent restriction in cultured cells and in mice. This shows that SAMHD1 can
      restrict lentiviruses in vivo and that nucleotide starvation is an evolutionarily
      conserved antiviral mechanism. 

PMID- 23872950
TI  - Invigorating cancer prevention: proposing core competencies in cancer prevention
      research training.

PMID- 23872949
TI  - Oral cancer chemotherapy adherence and adherence assessment tools: a report from
      North Central Cancer Group Trial N0747 and a systematic review of the literature.
AB  - Oncologists are now prescribing more oral chemotherapy than ever before, thus
      placing the onus for taking the right dose at the right time under the right
      circumstances directly on the patient. This study was undertaken to understand
      emerging adherence issues and to explore available adherence assessment tools.
      This two-part study (1) examined N0747, a randomized phase II trial that tested
      the oral agents, sunitinib and capecitabine, in patients with metastatic
      esophageal cancer from an adherence standpoint, and (2) conducted a systematic
      review to compile and assess adherence tools that can be used in future clinical
      trials. First, in N0747, patients were assigned to sunitinib and capecitabine
      versus capecitabine; 53 chemotherapy cycles were prescribed to this 12-patient
      cohort. Nearly all patients denoted that they "always or almost always" took
      their pills as prescribed, and two patients who reported lack of full adherence
      suffered from grade 3+ adverse events. Surprisingly, however, over 14 cycles, 9
      patients reported grade 3+ toxicity but checked "always or almost always" to
      describe their adherence. No relationships were observed between adherence and
      cancer outcomes. Secondly, 21 articles identified the following adherence tools:
      (1) healthcare providers' interviews, (2) patient-reported adherence with
      diaries/calendars, (3) patient-completed adherence scales, (4) medication event
      monitoring, (5) automated voice response, (6) drug/metabolite assays, and (7)
      prescription databases. Of note, only the automated voice response seems capable
      of real-time detection of over-adherence, as observed in N0747. Oral chemotherapy
      adherence should be further studied, particularly from the standpoint of over
      adherence.

PMID- 23872951
TI  - Breaking bad news: current prospective and practical guideline for Muslim
      countries.
AB  - Breaking bad news is one of the most distressing tasks which face physicians on
      daily basis; however, only few doctors receive formal training on this task.
      Disappointingly, the current status of the "breaking bad news" sector in health
      care systems in the Muslim countries is largely unknown. The following article
      attempts to address the current status of breaking bad news in the health care
      sector in Muslim countries and devises a practical protocol which provides a
      stepwise framework for breaking bad news in Muslim countries. 

PMID- 23872952
TI  - Handgrip strength predicts survival and is associated with markers of clinical
      and functional outcomes in advanced cancer patients.
AB  - PURPOSE: Handgrip strength (HGS) has been shown to predict survival and is
      associated with changes in body composition, nutritional status, inflammation,
      and functional ability in several chronic disease conditions. Whether similar
      relationships exist between HGS and clinical outcomes in patients with advanced
      cancer are currently unknown. We evaluated the association between HGS and
      survival as well as several key markers of body composition (e.g., sarcopenia),
      subjective performance measures (e.g., quality of life), and muscle strength
      (e.g., isokinetic torque of the quadriceps) in patients with advanced forms of
      non-small cell lung and gastrointestinal cancers. METHODS: A consecutive cohort
      of 203 patients with advanced cancer was enrolled and categorized into three HGS
      percentiles (e.g., >=50th, 25th, and <=10th) according to published normative
      values. Multivariate regression analyses were used to test for independent
      associations between HGS and survival, sarcopenia, quality of life (QoL), and
      lower extremity muscle strength as well as key biological markers (e.g.,
      hemoglobin, albumin, and C-reactive protein) while controlling for age, gender,
      cancer diagnosis, treatment (chemotherapy/radiotherapy), medications, and time
      from diagnosis to assessment. RESULTS: When compared to HGS >=50th, patients in
      the HGS <=10th percentile had lower BMI (B, -2.5 kg/m(2); 95% CI, -4.5 to -0.45),
      shorter survival (hazard ratio, 3.2; 2.0-5.1), lower hemoglobin (-19.70 g/L; 
      27.28 to -12.13) and albumin (-4.99 g/L; -7.85 to -2.13), greater occurrence of
      sarcopenia (odds ratio, 9.53; 1.95-46.55), lower isokinetic torque of the
      quadriceps at both 60 degrees /s (-30.6 Nm; -57.9 to -3.3) and 120 degrees /s (
      25.1 Nm; -46.4 to -3.7), lower QoL (-1.6 on McGill Quality of Life Questionnaire
      scale; -2.5 to -0.6), higher levels of fatigue (18.8 on Brief Fatigue Inventory
      scale; 4.7 -32.9), poorer performance status (0.75 on Eastern Cooperative
      Oncology Group Performance Status scale; 0.34-1.15), lower fat mass (-7.4 kg; 
      14.4 to -0.5), and lower lean body mass (-6.5 kg; -10.3 to -2.8). CONCLUSIONS:
      HGS is independently associated with survival and important biological,
      functional, and quality of life characteristics in advanced cancer patients.
      Patients presenting with very low percentiles with respect to their handgrip
      assessment may require timely referral to supportive and/or palliative care
      services.

PMID- 23872954
TI  - DUSP10 gene polymorphism and risk of colorectal cancer in the Han Chinese
      population.
AB  - Dual-specificity protein phosphatases (DUSP) negatively regulate members of the
      mitogen-activated protein kinase superfamily, which is associated with cellular
      proliferation and differentiation. A recent study suggests that DUSP10 is
      frequently upregulated in colorectal cancer (CRC). Our study aimed to assess
      whether DUSP10 contributes to the risk of CRC. We analyzed nine tag single
      nucleotide polymorphisms (tSNPs) of DUSP10 in a case-control study of Han Chinese
      by the chi2-test and the SHEsis software. We found that two tSNPs (rs908858,
      P=0.00004; rs11118838, P=0.02510) were significantly associated with CRC using
      the chi2-test. Using the SHEsis software, six tSNPs (rs12041033, rs17010629,
      rs12724393, rs12036163, rs11118838, rs12044821) were found in the same linkage
      disequilibrium block. Within this linkage disequilibrium block, haplotype
      'CTCAAC' showed an increased risk of CRC by 42%. By global haplotype analysis, we
      found that the haplotype 'ACTCAACTA' may increase the risk of CRC by ~53%; the
      haplotype 'GCCCACCCA' may decrease the risk by ~46%. Our results, combined with
      previous studies, suggest that certain mutations in DUSP10 correlate with the
      incidence of CRC. Thus, the function of the DUSP10 gene product may contribute
      toward CRC in the Han Chinese population.

PMID- 23872953
TI  - Dietary factors and risk for advanced prostate cancer.
AB  - Prostate cancer is the second most common cancer among men worldwide. Although
      some nutrients have been linked to the development of total prostate cancer, it
      remains unclear whether these nutrients modulate the risk of its clinically
      significant form - advanced tumor. Therefore, this study sought to perform a
      systematic review of the literature on this topic. The papers reviewed were
      identified from PubMed using keywords diet and advanced, metastatic, or lethal
      prostate cancer. A total of 46 papers published until September 2012 met our
      eligibility criteria and thus were evaluated in this review. Epidemiologic
      studies have shown that, overall, the habitual consumption of a diet high in
      saturated fat, well-done meats, and calcium is associated with an increased risk
      for advanced prostate cancer. An inconsistent association was observed for intake
      of total meat, fruits, and vegetables. Although most case-control studies suggest
      that intake of these nutrients or foods significantly alters advanced prostate
      cancer risk, cohort studies yielded mixed results. No apparent effect of fish and
      zinc intake on advanced prostate cancer was found in most epidemiologic studies.
      Epidemiologic studies conducted to date have revealed that some dietary factors
      modulate the risk for advanced prostate cancer. If these findings are confirmed
      by more adequately powered epidemiologic studies, especially prospective cohort
      studies that measure the nutrients and their biochemical indicators, the risk of
      advanced prostate cancer, which is fatal and thus clinically significant, may be
      reduced by dietary modification or chemoprevention. 

PMID- 23872955
TI  - Freezing out all-optical poling dynamics of azophenylcarbazole molecules in
      polycarbonate.
AB  - In this work we have extended the application of a theoretical model describing
      the processes of all-optical poling of isomerizable molecules while taking into
      consideration the thermoisomerization related findings presented in the
      literature. A model describing all-optical poling transients using a three
      relaxation rate approach was contrasted with the experimental results of
      azophenylcarbazole doped polycarbonate measured in a wide range of temperatures
      from 150 to 300 K, thus covering the beta transition for the host. By means of a
      long timescale and low temperature, we were able to better resolve the
      thermoisomerization and orientational diffusion processes. The cis->trans
      thermoisomerization relaxation rates k1 and k2 were obtained in the range 10(-5)
      to 10(-2) s(-1) and the relaxation rate k3 of the orientational diffusion of the
      trans isomer in the range 10(-6) to 10(-4) s(-1). The rates exhibited diverse
      temperature dependent behaviors: the two lowest (k2,k3) manifested Arrhenius type
      dependencies (Ek2 = 157 meV), whereas, the highest (k1) showed a temperature
      dependence that is non-Arrhenius, or undistinguished for our experimental
      conditions. The latter was interpreted using the geometrical "adjustment" model.
      By investigating chromophore-polymer systems at temperatures far below Tg, we
      were able to uncover the situation when the cis->trans transition is switched-off
      and the orientational randomization is suppressed. Thus, we could consider the
      chromophores as "frozen". 

PMID- 23872956
TI  - The HIF-1 transcription complex is essential for translational control of myeloid
      hematopoietic cell function by maintaining mTOR phosphorylation.
AB  - Mammalian myeloid cells are crucial effectors of host innate immune defense.
      Normal and pathological responses of these cells require adaptation to signaling
      stress through the hypoxia-inducible factor 1 (HIF-1) transcription complex.
      Adapted cells activate the mammalian target of rapamycin (mTOR), via S2448
      phosphorylation, which induces de novo translation of vital signaling proteins.
      However, the molecular mechanisms underlying this signaling dogma remain unclear.
      Here, we demonstrate for the first time that inactivation of HIF-1, by silencing
      its inducible alpha subunit, significantly decreases mTOR S2448 phosphorylation
      caused by ligand-dependent activation of human myeloid leukemia cells. This shows
      that HIF-1 is essential for the activation of mTOR and serves at a crucial
      juncture of myeloid cell function in both in vitro and in vivo systems. 

PMID- 23872957
TI  - Increase in rRNA content in a Saccharomyces cerevisiae suppressor strain from
      rrn10 disruptant by rDNA cluster duplication.
AB  - Breeding of yeast strains with higher RNA content is important because yeast RNA
      is a significant source of 5'-ribonucleotides, which have considerable use in
      both the food and pharmaceutical industries. Ribosomal RNA (rRNA) is an important
      source of yeast RNA as it accounts for about 80 % of total RNA content. We
      previously reported a dominant suppressor mutant of an rrn10 disruptant named
      SupE, which displays the ability not only to restore diminished RNA content
      caused by rrn10 disruption but also to increase the transcription level of
      ribosomal protein (RP) genes on an ?rrn10 background in Saccharomyces cerevisiae.
      Here, to construct an S. cerevisiae strain with higher RNA content, we
      investigated the effect of increasing the copy number of the rDNA gene on a
      ?rrn10 SUPE background. We successfully constructed a SupE strain with two copies
      of the rDNA cluster (ca. 300 rDNA genes) by using chromosome-splitting
      technology. The RNA content of this strain was 61 % higher than that of the SupE
      strain with a single copy of the rDNA cluster (ca. 150 rDNA genes), and 40 %
      higher than that of the wild-type strain with two copies of the rDNA cluster. A
      further increase in RNA content of 47 % was achieved by multicopy expression of
      the RPL40A gene in the SupE strain with two copies of the rDNA cluster. These
      observations suggest that we have constructed an S. cerevisiae strain with two
      copies of the rDNA cluster, which has achieved a considerably higher RNA content.
      Furthermore, the strategy taken in this study provides an effective approach to
      constructing S. cerevisiae strains with high potential for yeast food
      biotechnology.

PMID- 23872958
TI  - Cholesterol-lowering probiotics: in vitro selection and in vivo testing of
      bifidobacteria.
AB  - Thirty-four strains of bifidobacteria belonging to Bifidobacterium adolescentis,
      Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve,
      Bifidobacterium longum, and Bifidobacterium pseu-docatenulatum were assayed in
      vitro for the ability to assimilate cholesterol and for bile salt hydrolase (BSH)
      against glycocholic and taurodeoxycholic acids (GCA and TDCA). Cholesterol
      assimilation was peculiar characteristic of two strains belonging to the species
      B. bifidum (B. bifidum MB 107 and B. bifidum MB 109), which removed 81 and 50 mg
      of cholesterol per gram of biomass, being the median of specific cholesterol
      absorption by bifidobacteria 19 mg/g. Significant differences in BSH activities
      were not established among bifidobacterial species. However, the screening
      resulted in the selection of promising strains able to efficiently deconjugate
      GCA and TDCA. No relationship was recognized between BSH phenotype and the extent
      of cholesterol assimilation. On the basis of cholesterol assimilation or BSHGCA
      and BSHTDCA activities, B. bifidum MB 109 (DSMZ 23731), B. breve MB 113 (DSMZ
      23732), and B. animalis subsp. lactis MB 2409 (DSMZ 23733) were combined in a
      probiotic mixture to be fed to hypercholesterolemic rats. The administration of
      this probiotic formulation resulted in a significant reduction of total
      cholesterol and low-density cholesterol (LDL-C), whereas it did not affect high
      density cholesterol (HDL-C) and HDL-C/LDL-C ratio. 

PMID- 23872959
TI  - Short-term adaptation improves the fermentation performance of Saccharomyces
      cerevisiae in the presence of acetic acid at low pH.
AB  - The release of acetic acid due to deacetylation of the hemicellulose fraction
      during the treatment of lignocellulosic biomass contributes to the inhibitory
      character of the generated hydrolysates. In the present study, we identified a
      strain-independent adaptation protocol consisting of pre-cultivating the strain
      at pH 5.0 in the presence of at least 4 g L-1 acetic acid that enabled aerobic
      growth and improved fermentation performance of Saccharomyces cerevisiae cells at
      low pH (3.7) and in the presence of inhibitory levels of acetic acid (6 g L-1).
      During anaerobic cultivation with adapted cells of strain TMB3500, the specific
      ethanol production rate was increased, reducing the fermentation time to 48 %.

PMID- 23872960
TI  - Isoflavone production in Cyclopia subternata Vogel (honeybush) suspension
      cultures grown in shake flasks and stirred-tank bioreactor.
AB  - Suspension cultures of the endemic South-African plant Cyclopia subternata were
      established for the first time and evaluated for the presence of isoflavones. The
      influence of light, as well as medium supplementation strategies with
      phenylalanine, casein hydrolysate and coconut water on biomass growth and
      isoflavone production were examined. The highest levels of 7-O-beta-glucosides of
      calycosin, pseudobaptigenin and formononetin (275.57, 125.37 and 147.28 mg/100 g
      DW, respectively) were recorded for cultures grown in the absence of light,
      whereas coconut water substantially promoted biomass growth. Cell suspensions
      were subsequently grown in the 2-l stirred-tank bioreactor. Maximum productivity
      of 7-O-beta-glucosides of calycosin, pseudobaptigenin and formononetin (0.96,
      0.44 and 0.22 mg l(-1) day(-1), respectively) in bioreactor-cultivated cells was
      obtained for biomass grown in the dark and supplemented with coconut water. The
      results indicate that C. subternata suspension cultures can be utilised for the
      production of the specified isoflavone derivatives absent in the intact plant. 

PMID- 23872961
TI  - Inducible cell lysis systems in microbial production of bio-based chemicals.
AB  - The release of products from microbial cells is an essential process for
      industrial scale production of bio-based chemicals. However, traditional methods
      of cell lysis, e.g., mechanical disruption, chemical solvent extraction, and
      immobilized enzyme degradation, account for a large share of the total production
      cost. Thus, an efficient cell lysis system is required to lower the cost. This
      review has focused on our current knowledge of two cell lysis systems,
      bacteriophage holin-endolysin system, and lipid enzyme hydrolysis system. These
      systems are controlled by conditionally inducible regulatory apparatus and
      applied in microbial production of fatty acids and polyhydroxyalkanoates.
      Moreover, toxin-antitoxin system is also suggested as alternative for its
      potential applications in cell lysis. Compared with traditional methods of cell
      disruption, the inducible cell lysis systems are more economically feasible and
      easier to control and show a promising perspective in industrial production of
      bio-based chemicals. 

PMID- 23872962
TI  - Four new compounds from Imperata cylindrica.
AB  - Four new compounds, impecylone (1), deacetylimpecyloside (2), seguinoside K 4
      methylether (3) and impecylenolide (4), were isolated from Imperata cylindrica
      along with two known compounds, impecyloside (5) and seguinoside K (6). Their
      structures were elucidated mainly by spectroscopic analyses including 1D- and 2D
      NMR techniques, and the absolute configuration of 1 was confirmed by X-ray
      diffraction analysis. In calcium assay, the result indicated that compounds 1, 2,
      4 and 5 cannot obviously inhibit the calcium peak value compared with the
      negative control, and suggested that the four compounds could not have anti
      inflammatory activity. 

PMID- 23872963
TI  - Facial paralysis grading system: a new and simple smile excursion score for
      evaluating facial reanimation surgery.
AB  - BACKGROUND: Various facial paralysis grading systems have been introduced to
      evaluate the results of both spontaneous recovery and facial palsy
      reconstruction. The aim of the present study was to introduce and evaluate an
      objective new and quick Smile Excursion Score system which is readily applicable
      and easy to follow. It has been applied over the past 25 years for preoperative
      and postoperative result evaluation of smile reconstruction at Chang Gung
      Memorial Hospital. METHODS: A standardized evaluation method was described for
      the assessment of the upper lip movement preoperatively and postoperatively with
      at least 1 year follow-up after functioning muscle transplantation. The
      evaluation was scored by the number of maxillary teeth exposed when smiling with
      teeth showing. Reliability of this technique was assessed by using 3 independent
      examiners who each evaluated the smiles of 34 unilateral facial paralysis
      patients 4 times, creating 408 sets of measurements. RESULTS: The intraclass
      correlation coefficients for interrater and intrarater reliability exceeded 0.94,
      which is considered as excellent and reliable. CONCLUSIONS: Chuang's Smile
      Excursion Score system is simple, quick, and accurate in evaluating smile after
      reanimation of paralyzed face effecting free functional muscle transplantation
      with no additional tools.

PMID- 23872964
TI  - Prevention of necrosis of adjacent expanded flaps by surgical delay.
AB  - Although expanded flaps have been shown to survive longer than unexpanded flaps,
      flap necrosis still occurs, particularly when a deep back cut has been made.
      Overcautious design can avoid necrosis but leads to inefficient usage of the
      expanded flap. In this study, we tested a surgical delay method to prevent
      partial necrosis and maximize the use of the expanded flap. Ten patients with 13
      expanders were included in this series. The surgical delay was performed 2 weeks
      before the final flap transfer. The survival of the delayed flaps was compared
      with that in previous cases without surgical delay. All 13 expanded flaps
      exhibited complete survival, which was significantly better than the 27.5%
      partial flap necrosis observed in nondelayed cases. Surgical delay can decrease
      the risk of necrosis in an expanded flap caused by a back cut and can thus
      maximize flap use. 

PMID- 23872965
TI  - Anterior retrograde approach to the myofascial temporalis muscle for orbital
      reconstruction: series of 9 consecutive cases.
AB  - BACKGROUND: Among the reconstructive options after orbital exenteration, the
      temporalis myofascial flap (TMF) has been widely recognized as the one of the
      best available solutions. We think that the hemicoronal approach to harvest the
      TMF represents a disadvantage so we adopted a modified approach that we named the
      anterior retrograde approach to the TMF. METHODS: Nine patients with malignant
      orbital tumors underwent orbital exenteration and primary reconstruction with TMF
      harvested with the anterior retrograde approach. The temporalis muscle was widely
      exposed through the anterior incision used to perform the orbital exenteration.
      The harvested flap was then rotated and insetted to fill the orbital cavity.
      RESULTS: Neither cases of total/partial flap failure nor local/regional
      recurrence of tumor were recorded. The technique showed a significant reduction
      of morbidity, surgical time, and blood loss compared with the traditional
      technique. CONCLUSIONS: We think that the anterior retrograde approach should be
      considered as a valid alternative to the traditional hemicoronal approach.

PMID- 23872966
TI  - An introduction to high-throughput sequencing experiments: design and
      bioinformatics analysis.
AB  - The dramatic fall in the cost of DNA sequencing has revolutionized the
      experiments within reach in the life sciences. Here we provide an introduction
      for the domains of analyses possible using high-throughput sequencing,
      distinguishing between "counting" and "reading" applications. We discuss the
      steps in designing a high-throughput sequencing experiment, introduce the most
      widely used applications, and describe basic sequencing concepts. We review the
      various software programs available for many of the bioinformatics analysis
      required to make sense of the sequencing data. We hope that this introduction
      will be accessible to biologists with no previous background in bioinformatics,
      yet with a keen interest in applying the power of high-throughput sequencing in
      their research. 

PMID- 23872967
TI  - Compressing resequencing data with GReEn.
AB  - Genome sequencing centers are flooding the scientific community with data. A
      single sequencing machine can nowadays generate more data in one day than any
      existing machine could have produced throughout the entire year of 2005.
      Therefore, the pressure for efficient sequencing data compression algorithms is
      very high and is being felt worldwide. Here, we describe GReEn (Genome
      Resequencing Encoding), a compression tool recently proposed for compressing
      genome resequencing data using a reference genome sequence. 

PMID- 23872968
TI  - On the accuracy of short read mapping.
AB  - The development of high-throughput sequencing technologies has revolutionized the
      way we study genomes and gene regulation. In a single experiment, millions of
      reads are produced. To gain knowledge from these experiments the first thing to
      be done is finding the genomic origin of the reads, i.e., mapping the reads to a
      reference genome. In this new situation, conventional alignment tools are
      obsolete, as they cannot handle this huge amount of data in a reasonable amount
      of time. Thus, new mapping algorithms have been developed, which are fast at the
      expense of a small decrease in accuracy. In this chapter we discuss the current
      problems in short read mapping and show that mapping reads correctly is a
      nontrivial task. Through simple experiments with both real and synthetic data, we
      demonstrate that different mappers can give different results depending on the
      type of data, and that a considerable fraction of uniquely mapped reads is
      potentially mapped to an incorrect location. Furthermore, we provide simple
      statistical results on the expected number of random matches in a genome (E
      value) and the probability of a random match as a function of read length.
      Finally, we show that quality scores contain valuable information for mapping and
      why mapping quality should be evaluated in a probabilistic manner. In the end, we
      discuss the potential of improving the performance of current methods by
      considering these quality scores in a probabilistic mapping program.

PMID- 23872969
TI  - Statistical modeling of coverage in high-throughput data.
AB  - In high-throughput sequencing experiments, the number of reads mapping to a
      genomic region, also known as the "coverage" or "coverage depth," is often used
      as a proxy for the abundance of the underlying genomic region in the sample. The
      abundance, in turn, can be used for many purposes including calling SNPs,
      estimating the allele frequency in a pool of individuals, identifying copy number
      variations, and identifying differentially expressed shRNAs in shRNA-seq
      experiments.In this chapter we describe the fundamentals of statistical modeling
      of coverage depth and discuss the problems of estimation and inference in the
      relevant experimental scenarios.

PMID- 23872970
TI  - Assembly algorithms for deep sequencing data: basics and pitfalls.
AB  - Our ability to sequence the genomic data at our disposal is limited. At each
      experiment we can sequence reliably only a short fraction of even the smallest
      genome. We are then faced with the challenge of assembly-combining the short
      patches we have into a correct reconstruction of as large as possible a fragment
      of the original sample. The problem has been thoroughly researched and many
      commercial and academic tools exist to carry it out. However due to basic
      features of the problem the results of even our best efforts will be sometimes
      disappointing for the researcher. In this chapter we will try to explain why the
      assembly problem is so hard, what future directions may alleviate it in the near
      future, and what can be realistically expected from a current assembly
      experiment. 

PMID- 23872971
TI  - Short read mapping for exome sequencing.
AB  - Mapping short reads to the reference genome is very often the prerequisite for
      applications utilizing the next-generation sequencing technologies. A dozen of
      software tools developed for this purpose have been widely used. But many
      practical issues remained when utilizing them to build a computational pipeline
      for downstream analyses. In this chapter, we describe the read mapping procedures
      adopted in our lab for the exome sequencing studies as an example to illustrate
      those practical details. 

PMID- 23872972
TI  - Profiling short tandem repeats from short reads.
AB  - Short tandem repeats (STRs), also known as microsatellites, have a wide range of
      applications, including medical genetics, forensics, and population genetics.
      High-throughput sequencing has the potential to profile large numbers of STRs,
      but cumbersome gapped alignment and STR-specific noise patterns hamper this task.
      We recently developed an algorithm, called lobSTR, to overcome these challenges
      and to accurately profile STRs from short reads. Here we describe how to use
      lobSTR to call STR variations from high-throughput sequencing datasets and to
      diagnose the quality of the calls. 

PMID- 23872973
TI  - Exome sequencing analysis: a guide to disease variant detection.
AB  - Whole exome sequencing presents a powerful tool to study rare genetic disorders.
      The most challenging part of using exome sequencing for the purpose of disease
      causing variant detection is analyzing, interpreting, and filtering the large
      number of detected variants. In this chapter we provide a comprehensive
      description of the various steps required for such an analysis. We address
      strategies in selecting samples to sequence, and technical considerations
      involved in exome sequencing. We then discuss how to identify variants, and
      methods for first annotating detected variants using characteristics such as
      allele frequency, location in the genome, and predicted severity, and then
      classifying and prioritizing the detected variants based on those annotations.
      Finally, we review possible gene annotations that may help to establish a
      relationship between genes carrying high-priority variants and the phenotype in
      question, in order to identify the most likely causative mutations. 

PMID- 23872974
TI  - Identifying RNA editing sites in miRNAs by deep sequencing.
AB  - Deep sequencing has many possible applications; one of them is the identification
      and quantification of RNA editing sites. The most common type of RNA editing is
      adenosine to inosine (A-to-I) editing. A prerequisite for this editing process is
      a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the
      microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are
      affected by A-to-I editing. Indeed, tens of editing sites were found in miRNAs,
      some of which change the miRNA binding specificity. Here, we describe a protocol
      for the identification of RNA editing sites in mature miRNAs using deep
      sequencing data. 

PMID- 23872975
TI  - Identifying differential alternative splicing events from RNA sequencing data
      using RNASeq-MATS.
AB  - RNA sequencing (RNA-Seq) has emerged as a powerful and increasingly cost
      effective technology for analysis of transcriptomes. RNA-Seq has several
      significant advantages over gene expression microarrays, including its high
      sensitivity and accuracy, broad dynamic range, nucleotide-level resolution,
      ability to detect novel mRNA transcripts, and ability to analyze pre-mRNA
      alternative splicing. A major application of RNA-Seq is to detect differential
      alternative splicing, i.e., differences in exon splicing patterns among different
      biological conditions. We recently developed a statistical method multivariate
      analysis of transcript splicing (MATS) for detecting differential alternative
      splicing events from RNA-Seq data. Here, we describe a computational pipeline
      RNASeq-MATS based on the MATS algorithm. This pipeline automatically detects and
      analyzes differential alternative splicing events corresponding to all major
      types of alternative splicing patterns from RNA-Seq data.

PMID- 23872976
TI  - Optimizing detection of transcription factor-binding sites in ChIP-seq
      experiments.
AB  - Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) offers a
      powerful means to study transcription factor binding on a genome-wide scale.
      While a number of advanced software packages have already become available for
      identifying ChIP-seq-binding sites, it has become evident that the choice of the
      package together with its adjustable parameters can considerably affect the
      biological conclusions made from the data. Therefore, to aid these choices, we
      have recently introduced a reproducibility-optimization procedure, which
      computationally adjusts the parameters of the popular peak detection algorithms
      for each ChIP-seq data separately. Here, we provide a detailed description of the
      procedure together with practical guidelines on how to apply its implementation,
      the peakROTS R-package, in a given ChIP-seq experiment.

PMID- 23872977
TI  - Statistical analysis of ChIP-seq data with MOSAiCS.
AB  - Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq)
      is invaluable for identifying genome-wide binding of transcription factors and
      mapping of epigenomic profiles. We present a statistical protocol for analyzing
      ChIP-seq data. We describe guidelines for data preprocessing and quality control
      and provide detailed examples of identifying ChIP-enriched regions using the
      Bioconductor package "mosaics."

PMID- 23872978
TI  - Detection of reverse transcriptase termination sites using cDNA ligation and
      massive parallel sequencing.
AB  - Detection of reverse transcriptase termination sites is important in many
      different applications, such as structural probing of RNAs, rapid amplification
      of cDNA 5' ends (5' RACE), cap analysis of gene expression, and detection of RNA
      modifications and protein-RNA cross-links. The throughput of these methods can be
      increased by applying massive parallel sequencing technologies.Here, we describe
      a versatile method for detection of reverse transcriptase termination sites based
      on ligation of an adapter to the 3' end of cDNA with bacteriophage TS2126 RNA
      ligase (CircLigaseTM). In the following PCR amplification, Illumina adapters and
      index sequences are introduced, thereby allowing amplicons to be pooled and
      sequenced on the standard Illumina platform for genomic DNA sequencing. Moreover,
      we demonstrate how to map sequencing reads and perform analysis of the sequencing
      data with freely available tools that do not require formal bioinformatics
      training. As an example, we apply the method to detection of transcription start
      sites in mouse liver cells.

PMID- 23872979
TI  - Dry-gel conversion synthesis of Cr-MIL-101 aided by grinding: high surface area
      and high yield synthesis with minimum purification.
AB  - A dry gel conversion synthesis aided by fine-grinding of the synthesis precursors
      produces a MIL-101 product with a high surface area greater than 4100 m(2) g(-1)
      and a product yield approaching 90% in a very reproducible manner after only
      simple water washing. 

PMID- 23872980
TI  - Role of hysteroscopy and endometrial biopsy in women with unexplained
      infertility.
AB  - OBJECTIVES: This study was designed to evaluate the role of hysteroscopy and
      endometrial biopsy in women with unexplained infertility. PATIENTS AND METHODS:
      Women with unexplained infertility were included in this prospective study,
      evaluated with transvaginal sonography and diagnostic hysteroscopy. Diagnostic
      hysteroscopy was performed between the 7th and 11th day of the cycle. The
      criteria for hysteroscopic findings were based on the cervical canal, uterine
      cavity, endometrium, visualization of the ostium tubae and lesions of the utero
      tubal junction. After the hysteroscopic examination, endometrial biopsy was
      performed using a Pipelle endometrial suction curette. Patients were classified
      according to the hysteroscopy results into four groups: patients with no
      abnormality detected (14), patients with cervical abnormalities (six), patients
      with endometrial abnormalities (73) and patients with uterine abnormalities
      (seven). RESULTS: One hundred women with unexplained infertility were included.
      All patients underwent diagnostic hysteroscopy, except for seven patients: six
      patients had stenotic external or internal cervical ostium and one had inadequate
      visualization as the uterine cavity was filled with blood. Based on hysteroscopic
      findings, 31 patients were finally diagnosed with endometrial polyps; 14
      endometritis; 15 endometrial hyperplasia; six submucous myomas; seven
      intrauterine synechiae (73 cases = endometrial abnormalities group); seven
      congenital uterine anomalies (uterine abnormalities group), six cervical stenosis
      (cervical abnormalities group) and 14 women without any uterine abnormalities (no
      abnormalities group). Analysis of samples obtained using the Pipelle endometrial
      suction curette was non-diagnostic in 16 cases; the most common endometrial
      pathological feature detected by this analysis was endometritis (15%).
      CONCLUSIONS: Routine hysteroscopy and endometrial biopsy should be used as a
      basic part of the work-up for women with unexplained infertility.

PMID- 23872982
TI  - Use of insulin-like growth factor binding protein-1 for retrospective diagnosis
      of amniotic fluid embolism in first trimester.

PMID- 23872981
TI  - Non-invasively collected amniotic fluid as a source of possible biomarkers for
      premature rupture of membranes investigated by proteomic approach.
AB  - PURPOSE: Preterm delivery is one of the main causes of perinatal morbidity and
      mortality and it accounts for 75 % of perinatal mortality and more than half of
      the long-term morbidity. We applied a proteomic approach based on mass
      spectrometry (MS) for biomarkers discovery of preterm premature rupture of
      membranes (pPROM) by investigating amniotic fluid (AF) invasively and non
      invasively collected. METHODS: Amniotic fluid was obtained from vagina of women
      with pPROM (group 1), PROM at term (group 2) and by genetic amniocentesis (group
      3). Pre-fractionated AF proteome was analyzed through matrix assisted laser
      desorption ionization-time of flight (MALDI-TOF) MS. The characterization of
      proteins/peptides of interest was obtained by high performance liquid
      chromatography-electrospray tandem MS. RESULTS: Three peptides overexpressed in
      pPROM and able to discriminate the groups 1 and 2 were detected. One peptide was
      identified as the fragment Gly452LAVPDGPLGLPPKPro466 of the protein KIAA1522,
      expressed by fetal brain and liver. This peptide was overexpressed in a patient
      of the group 3, completely asymptomatic at the time of the amniocentesis, who
      later developed pPROM. CONCLUSION: Amniotic fluid invasively and non-invasively
      collected can be analyzed by MALDI-TOF MS to obtain proteomic profiles. Proteomic
      analysis identified a peptide with promising diagnostic capability for pPROM.

PMID- 23872983
TI  - Identification of molecular determinants for a potent mammalian TRPA1 antagonist
      by utilizing species differences.
AB  - The transient receptor potential A1 (TRPA1) receptor is a member of the TRP
      family and an excitatory nonselective cation channel. An increasing body of
      evidence suggests that TRPA1 acts as a nociceptor for various chemicals and
      physical stimuli. Thus, many TRPA1 antagonists have been developed as analgesic
      agents. Recently, we found that AP18, a mammalian TRPA1 antagonist, does not
      inhibit heterologously expressed western clawed frog TRPA1 (fTRPA1). Here, we
      show that fTRPA1 is also insensitive to A967079, one of the most potent mammalian
      TRPA1 antagonists. Neither heterologously nor endogenously expressed fTRPA1 was
      inhibited by A967079 upon activation by TRPA1 agonists. Mutant channel analyses
      revealed that two specific amino acid residues located within the putative fifth
      transmembrane domain were involved in the inhibitory action of A967079. Our
      findings and previous reports based on species differences in the sensitivity to
      TRPA1 antagonists provide novel insights into the structure-function relationship
      of TRPA1 and supply useful information in the search for new analgesic medicines
      targeting TRPA1. 

PMID- 23872984
TI  - A post-synthetic approach for the synthesis of 2'-O-methyldithiomethyl-modified
      oligonucleotides responsive to a reducing environment.
AB  - Based on a novel concept, a Reducing-Environment-Dependent Uncatalyzed Chemical
      Transforming RNA, "REDUCT RNA", we established a post-synthetic approach for the
      synthesis of 2'-O-methyldithiomethyl-modified oligonucleotides from 2'-O-(2,4,6
      trimethoxybenzylthiomethyl)-oligonucleotides by treatment with
      dimethyl(methylthio)sulfonium tetrafluoroborate. 2'-O-methyldithiomethyl
      oligonucleotides were easily converted into 2'-hydroxy oligonucleotides under
      reducing conditions, such as those found in the intracellular environment. 

PMID- 23872985
TI  - The direct magnetoelectric effect in ferroelectric-ferromagnetic epitaxial
      heterostructures.
AB  - Ferroelectric (FE) and ferromagnetic (FM) materials engineered in horizontal
      heterostructures allow interface-mediated magnetoelectric coupling. The so-called
      converse magnetoelectric effect (CME) has been already demonstrated by electric
      field poling of the ferroelectric layers and subsequent modification of the
      magnetic state of adjacent ferromagnetic layers by strain effects and/or free
      carrier density tuning. Here we focus on the direct magnetoelectric effect (DME)
      where the dielectric state of a ferroelectric thin film is modified by a magnetic
      field. Ferroelectric BaTiO3 (BTO) and ferromagnetic CoFe2O4 (CFO) oxide thin
      films have been used to create epitaxial FE/FM and FM/FE heterostructures on
      SrTiO3(001) substrates buffered with metallic SrRuO3. It will be shown that large
      ferroelectric polarization and DME can be obtained by appropriate selection of
      the stacking order of the FE and FM films and their relative thicknesses. The
      dielectric permittivity, at the structural transitions of BTO, is strongly
      modified (up to 36%) when measurements are performed under a magnetic field. Due
      to the insulating nature of the ferromagnetic layer and the concomitant absence
      of the electric-field effect, the observed DME effect solely results from the
      magnetostrictive response of CFO elastically coupled to the BTO layer. These
      findings show that appropriate architecture and materials selection allow
      overcoming substrate-induced clamping in multiferroic multi-layered films. 

PMID- 23872986
TI  - Demonstration of the retention of 64Cu-ATSM in cardiac myocytes using a novel
      incubation chamber for screening hypoxia-dependent radiotracers.
AB  - OBJECTIVE: We have designed a low-cost, reusable incubation system that allows
      cells to be cultured in either plated or suspension culture under complete
      atmospheric control for radiotracer characterization. We demonstrate its utility
      here in the first quantification of the hypoxia-dependent accumulation of Cu
      diacetyl bis(N4-methylthiosemicarbazone) (Cu-ATSM) in adult rat ventricular
      myocytes (ARVMs). MATERIALS AND METHODS: ARVMs were allowed to adhere overnight
      in 9 cm culture plates (2*10 cells/dish) or were used in suspension culture,
      placed inside the chamber and equilibrated with either oxic (95 or 21% O2/5% CO2)
      or anoxic gas (95% N2/5% CO2). Cu-ATSM of 100 kBq was administered, and the cells
      were incubated for 30 or 60 min. Cells were then harvested, counted and
      fractionated to determine intracellular Cu biodistribution. RESULTS: After 1 h,
      the average cellular Cu retention in plated ARVMs under oxygenated conditions was
      23.9 +/- 2.5 mBq/cell (95% O2), increasing to 27.3 +/- 5.1 under 21% O2 (P<0.05)
      and to 36.1 +/- 3.1 under 0% O2 (P<0.05). When ARVMs were cultured in suspension,
      normoxic-hypoxic contrast was less marked but still significant [63.2 +/- 14.1
      vs. 53.4 +/- 10.9% mBq/cell after 30 min (P<0.05)]. Sixty percent of tracer
      accumulated in the cytosol, and, although total cellular retention increased
      during hypoxia, there was no enrichment in any particular cellular compartment.
      CONCLUSION: This apparatus allows the conduction of radiotracer uptake studies in
      cells under complete atmospheric control, as evidenced by our first demonstration
      of the hypoxia-dependent uptake of Cu-ATSM in ventricular myocytes. It is ideally
      suited for screening, validating and characterizing novel hypoxia-selective
      radiotracers.

PMID- 23872987
TI  - Wandering-and wondering-about the pharmacological management of human
      infertility.

PMID- 23872988
TI  - Cognitive decline and oral health in middle-aged adults in the ARIC study.
AB  - Even before dementia becomes apparent, cognitive decline may contribute to
      deterioration in oral health. This cohort study of middle-aged adults evaluated
      associations of six-year change in cognitive function with oral health behaviors
      and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive
      function was measured at study visits in 1990-1992 and 1996-1998 with three
      tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and
      (c) Word Fluency (WF). Cognitive decline scores were computed as 'studentized'
      residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998,
      10,050 participants answered dental screening questions, and 5,878 of 8,782
      dentate participants received a comprehensive oral examination. Multiple
      regression models used cognitive change to predict oral health behaviors and
      conditions with adjustment for covariates. In the fully adjusted models, greater
      decline in all three measures of cognitive function was associated with increased
      odds of complete tooth loss. Greater decline in DSS and WF scores was associated
      with infrequent toothbrushing. Decline in WF scores was also associated with
      higher plaque levels. In these middle-aged adults, six-year cognitive decline was
      modestly associated with less frequent toothbrushing, plaque deposit, and greater
      odds of edentulism, but not with other oral behaviors or diseases.

PMID- 23872989
TI  - Involvement of gshAB in the interspecies competition within oral biofilm.
AB  - Although Streptococcus sanguinis has been reported to produce H2O2 to gain a
      competitive edge over Streptococcus mutans, the molecular mechanisms evolved by
      S. mutans to counter this "peer stress" are still to be identified. The current
      study was designed to investigate the ecological role of glutathione synthetase
      (gshAB) in the interspecies interaction between S. mutans and S. sanguinis. A
      gshAB in-frame deletion strain of S. mutans was constructed, and its phenotypic
      traits were characterized. The spatio-temporal interaction of the gshAB mutant
      with S. sanguinis was further investigated in a dual-species biofilm model by
      fluorescence in situ hybridization. We found that, although less tolerant for
      H2O2, the gshAB mutant produced more extracellular polysaccharides by up
      regulating gtfs expression, so as to cluster as condensed microcolonies. In
      addition, the mutant was more susceptible to the conditioned medium of S.
      sanguinis, and its competitiveness was significantly compromised. Taken together,
      we believe that gshAB is essential for the competitiveness and prevalence of S.
      mutans through detoxifying the H2O2 produced by S. sanguinis. Given the
      ecological importance of bacterial equilibrium within the oral biofilm, gshAB may
      represent a promising target to modulate the S. mutans/S. sanguinis ratio under
      cariogenic conditions, thus contributing to the management of dental caries.

PMID- 23872990
TI  - Structure of a kinesin-tubulin complex and implications for kinesin motility.
AB  - The typical function of kinesins is to transport cargo along microtubules.
      Binding of ATP to microtubule-attached motile kinesins leads to cargo
      displacement. To better understand the nature of the conformational changes that
      lead to the power stroke that moves a kinesin's load along a microtubule, we
      determined the X-ray structure of human kinesin-1 bound to alphabeta-tubulin. The
      structure defines the mechanism of microtubule-stimulated ATP hydrolysis, which
      releases the kinesin motor domain from microtubules. It also reveals the
      structural linkages that connect the ATP nucleotide to the kinesin neck linker, a
      15-amino acid segment C terminal to the catalytic core of the motor domain, to
      result in the power stroke. ATP binding to the microtubule-bound kinesin favors
      neck-linker docking. This biases the attachment of kinesin's second head in the
      direction of the movement, thus initiating each of the steps taken. 

PMID- 23872991
TI  - Noncoding RNAs prevent spreading of a repressive histone mark.
AB  - Transcription of eukaryotic genomes is more widespread than was previously
      anticipated and results in the production of many non-protein-coding RNAs
      (ncRNAs) whose functional relevance is poorly understood. Here we demonstrate
      that ncRNAs can counteract the encroachment of heterochromatin into neighboring
      euchromatin. We have identified a long ncRNA (termed BORDERLINE) that prevents
      spreading of the HP1 protein Swi6 and histone H3 Lys9 methylation beyond the
      pericentromeric repeat region of Schizosaccharomyces pombe chromosome 1.
      BORDERLINE RNAs act in a sequence-independent but locus-dependent manner and are
      processed by Dicer into short RNAs referred to as brdrRNAs. In contrast to
      canonical centromeric short interfering RNAs, brdrRNAs are rarely loaded onto
      Argonaute. Our analyses reveal an unexpected regulatory activity of ncRNAs in
      demarcating an epigenetically distinct chromosomal domain that could also be
      operational in other eukaryotes. 

PMID- 23872992
TI  - Dasatinib promotes the potential of proliferation and antitumor responses of
      human gammadeltaT cells in a long-term induction ex vivo environment.

PMID- 23872993
TI  - Win-win: how health care professionals and jail administrators can collaborate to
      address HIV behind bars.

PMID- 23872994
TI  - Results of a pilot test of a brief computer-assisted tailored HIV prevention
      intervention for use with a range of demographic and risk groups.
AB  - There is a need for brief HIV prevention interventions that can be disseminated
      and implemented widely. This article reports the results of a small randomized
      field experiment that compared the relative effects of a brief two-session
      counselor-delivered computer-tailored intervention and a control condition. The
      intervention is designed for use with African-American, non-Hispanic white and
      Hispanic males and females who may be at risk of HIV through unprotected sex,
      selling sex, male to male sex, injecting drug use or use of stimulants.
      Participants (n = 120) were recruited using a quota sampling approach and
      randomized using block randomization, which resulted in ten male and ten female
      participants of each racial/ethnic group (i.e. African-American, non-Hispanic
      white and Hispanic) being assigned to either the intervention or a control arm.
      In logistic regression analyses using a generalized estimating equations
      approach, at 3-month followup, participants in the intervention arm were more
      likely than participants in the control arm to report condom use at last sex
      (Odds ratio [OR] = 4.75; 95 % Confidence interval [CI] = 1.70-13.26; p = 0.003).
      The findings suggest that a brief tailored intervention may increase condom use.
      Larger studies with longer followups are needed to determine if these results can
      be replicated.

PMID- 23872996
TI  - Can a change in pH and pCO2 be used to monitor progress in patients undergoing
      noninvasive ventilation? A prospective cohort study.
AB  - The aim of this study was to compare changes in arterial and venous pH and pCO2
      in patients undergoing noninvasive ventilation and having serial blood gases to
      assess ventilatory function. This was a prospective observational study of
      patients with acute respiratory distress. The outcome of interest was agreement
      in change in pH and pCO2 between arterial and venous specimens [mean difference;
      95% limits of agreement (LoA)]. The average difference between the change in pH
      (v-a) was 0.001 pH units (LoA -0.7 to +0.7). The average difference between the
      change in pCO2 (v-a) was 0.04 mmHg (LoA -17.3 to +18.2). For both pH and pCO2, in
      the majority of cases, the direction of change was the same, although the
      magnitude was variable. The agreement between absolute change is reasonable for
      pH but not for pCO2. The direction of change agreed in most cases. Changes in
      venous pH and pCO2, in combination with clinical assessment, may be useful for
      assessing progress in patients undergoing noninvasive ventilation. 

PMID- 23872995
TI  - Acute pain management for patients under opioid maintenance treatment: what
      physicians do in emergency departments?
AB  - The aim of this study was to analyze the current practices on acute pain
      management of patients under opioid maintenance treatment (OMT), that is,
      buprenorphine or methadone. A total of 706 physicians were solicited through a
      national network to answer a survey about pain perception and analgesic
      strategies. Among the prescribers, 323 (46%) answered the survey: 131 (40%)
      physicians estimated that patients under OMT when exposed to an acute painful
      event feel more pain than other patients and 170 (53%) estimated that the
      patients felt the same amount of pain. Use of WHO step 1 analgesics was reported
      by 283 (88%) prescribers [264 (82%) prescribers reported use of paracetamol and
      178 (55%) reported use of NSAIDs]. Among the second-line analgesic drugs, the WHO
      step 3 analgesics (mainly morphine) were the most commonly reported [221
      physicians (68%)]. Overall, the results demonstrate the misconceptions of
      physicians on the pain tolerance of patients under OMT. Clinical studies and
      evidence-based guidelines are necessary to improve the therapeutic strategies for
      such patients in an emergency setting. 

PMID- 23872997
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: Propofol for migraine.
AB  - A short-cut review was carried out to establish whether propofol can improve
      recovery and reduce recurrence in patients presenting to the emergency department
      with acute migraine. Three studies were directly relevant to the question. The
      author, date and country of publication, patient group studied, study type,
      relevant outcomes, results and study weaknesses of these papers are shown in
      table 1. The clinical bottom line is that propofol might be a safe and effective
      therapy in the treatment of migraine, but more well-designed trials are needed to
      compare with standard therapy before widespread use is considered. 

PMID- 23872999
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: Therapeutic hypothermia for cardiac arrest of asphyxial origin.
AB  - A short-cut review was carried out to establish whether therapeutic hypothermia
      leads to improved neurological outcomes in adult patients who have sustained a
      cardiac arrest of asphyxial origin. Four studies were directly relevant to the
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these papers are
      shown in table 2. The clinical bottom line is that evidence for the use of
      therapeutic hypothermia in patients who are comatose following asphyxia is very
      limited, which precludes an evidence-based recommendation. A large, multicentre
      randomised controlled trial is necessary to answer this question. Our review has
      therefore highlighted an important area for further research. 

PMID- 23873000
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3: Super calprotectin will not expedite your discharge.
AB  - A short-cut review was carried out to establish whether measurement of the plasma
      calprotectin (S100A8/A9) level can be used to enable safe exclusion of acute
      appendicitis in children presenting to the emergency department with abdominal
      pain. Four studies were directly relevant to the question. The author, date and
      country of publication, patient group studied, study type, relevant outcomes,
      results and study weaknesses of these papers are shown in table 3. The clinical
      bottom line is that there is currently no evidence to suggest that serum
      calprotectin is superior to standard inflammatory markers for the exclusion or
      confirmation of suspected appendicitis. Clinical examination findings remain the
      cornerstone of surgical decision-making. 

PMID- 23873001
TI  - Short answer question case series: A dangerous cause of dyspnoea.

PMID- 23873004
TI  - Studies on postoperative neurological complications, particularly cognitive
      dysfunction.

PMID- 23873003
TI  - Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic
      review and meta-analysis.
AB  - PURPOSE: Neuroendocrine tumours (NET) are uncommon and may be localized in many
      different places in the body. Traditional imaging has mainly been performed with
      CT and somatostatin receptor scintigraphy (SRS). Recently, it has become possible
      to use somatostatin receptor PET/CT (SMSR PET) instead, which might improve
      diagnostic quality. To evaluate the diagnostic quality of SMSR PET we performed a
      meta-analysis as an update of a previous study published in 2012. METHODS: A
      literature search was performed searching MEDLINE, Embase and five other
      databases with a combination of the expressions "PET", "positron emission
      tomography", "neuroendocrine" and "NET". The search was updated to 31 December
      2012. Studies were selected which evaluated the sensitivity and specificity of
      SMSR PET for NET in the thorax or abdomen with a study size of at least eight
      patients. The methodological quality of the included studies was evaluated with
      QUADAS-2. RESULTS: Eight studies fulfilled the inclusion criteria and were
      selected for final analysis, and 14 articles from a previous meta-analysis were
      added for a total of 22 articles. A total of 2,105 patients were included in the
      studies, an increase from 567 in the previous meta-analysis. The pooled
      sensitivity was 93 % (95 % CI 91 - 94 %) and specificity 96 % (95 % CI 95 - 98
      %). The area under the summary ROC curve was 0.98 (95 % CI 0.95 - 1.0). In the
      previous meta-analysis the pooled sensitivity was 93 % (95 % CI 91 - 95 %) and
      specificity 91 % (95 % CI 82 - 97 %). CONCLUSION: SMSR PET has good diagnostic
      performance for evaluation of NET in the thorax and abdomen, better than SRS
      which has been the previous standard method. This meta-analysis gives further
      support for switching to SMSR PET.

PMID- 23873005
TI  - CT-guided nerve block: a review of the features of CT fluoroscopic guidance for
      nerve blocks.
AB  - Nerve blocks are an attractive interventional therapy in pain medicine. Several
      image guidance methods are available to secure the safety, accuracy, and
      selectivity of the nerve block. Computed tomography (CT) guidance provides a
      clear view of the vital viscera and vessels that should be avoided by the needle,
      and accurate placement of the needle tip before neuro-destructive procedures. A
      recent advance in CT technology is multi-slice CT fluoroscopy, which allows for
      rapid and easy correction of needle tip placement during insertion. To reduce the
      radiation dose for both patients and staff, the lowest radiation setting,
      intermittent quick-check fluoroscopy, and shortening of the planning scan should
      be used. Preliminary CT scanning with excellent spatial resolution may facilitate
      the application of CT fluoroscopic guidance to various types of nerve blocks.
      Here we review celiac plexus and splanchnic nerve blocks, trigeminal nerve block,
      neurolytic sympathectomy, and spinal intervention performed under CT guidance.
      Additional large-scale studies are needed to optimize the use of image guidance,
      especially CT fluoroscopy guidance, for nerve blocks. 

PMID- 23873006
TI  - Biomechanics and biocompatibility of woven spider silk meshes during remodeling
      in a rodent fascia replacement model.
AB  - OBJECTIVE: The aim of this study was to investigate biomechanical and immunogenic
      properties of spider silk meshes implanted as fascia replacement in a rat in vivo
      model. BACKGROUND: Meshes for hernia repair require optimal characteristics with
      regard to strength, elasticity, and cytocompatibility. Spider silk as a
      biomaterial with outstanding mechanical properties is potentially suitable for
      this application. METHODS: Commercially available meshes used for hernia repair
      (Surgisis and Ultrapro) were compared with handwoven meshes manufactured from
      native dragline silk of Nephila spp. All meshes were tied onto the paravertebral
      fascia, whereas sham-operated rats were sutured without mesh implantation. After
      4 or 14 days, 4 weeks, and 4 or 8 months, tissue samples were analyzed concerning
      inflammation and biointegration both by histological and biochemical methods and
      by biomechanical stability tests. RESULTS: Histological sections revealed rapid
      cell migration into the spider silk meshes with increased numbers of giant cells
      compared with controls with initial decomposition of silk fibers after 4 weeks.
      Four months postoperatively, spider silk was completely degraded with the
      formation of a stable scar verified by constant tensile strength values. Surgisis
      elicited excessive stability loss from day 4 to day 14 (P < 0.001), with distinct
      inflammatory reaction demonstrated by lymphocyte and neutrophil invasion.
      Ultrapro also showed decreasing strength and poor elongation behavior, whereas
      spider silk samples had the highest relative elongation (P < 0.05). CONCLUSIONS:
      Hand-manufactured spider silk meshes with good biocompatibility and beneficial
      mechanical properties seem superior to standard biological and synthetic meshes,
      implying an innovative alternative to currently used meshes for hernia repair.

PMID- 23873007
TI  - Pregnancy-associated myocardial infarction : case report and review of the
      literature.
AB  - Acute myocardial infarction (AMI) is a rare, but possibly catastrophic event
      during pregnancy, delivery, or puerperium, leading to a high mortality rate. It
      has different pathogenic mechanisms, such as atherosclerosis, vasospasm,
      thrombosis, and coronary dissection. Although MI has been reported in pregnant
      women at all stages of pregnancy and postpartum, it occurs more commonly in the
      third trimester. Pregnancy-associated MI most commonly involves the anterior
      wall. Pregnancy itself is an independent risk factor for MI, conferring a
      fourfold higher risk than that of nonpregnant women matched for age. We report
      the case of a 27-year-old primigravida at 30 weeks' gestation presenting with
      anterior MI, secondary to severe stenosis of the left anterior descending
      coronary artery, treated with emergency percutaneous coronary intervention. 

PMID- 23873008
TI  - Association of WPW syndrome and first-degree atrioventricular block:
      electrocardiographic diagnosis.

PMID- 23873009
TI  - Framingham risk score and severity of coronary artery disease.
AB  - OBJECTIVES: Coronary artery disease (CAD) is a leading cause of morbidity and
      mortality worldwide. Easy-to-perform and reliable parameters are needed to
      predict the presence and severity of CAD and to implement efficient diagnostic
      and therapeutic modalities. We aimed to examine whether the Framingham risk
      scoring system can be used for this purpose. METHODS: A total of 222 patients (96
      women, 126 men; mean age, 59.1 +/- 11.9 years) who underwent coronary angiography
      were enrolled in the study. Presence of > %50 stenosis in a coronary artery was
      assessed as critical CAD. The Framingham risk score (FRS) was calculated for each
      patient. CAD severity was assessed by the Gensini score. The relationship between
      the FRS and the Gensini score was analyzed by correlation and regression
      analyses. RESULTS: The mean Gensini score was 18.9 +/- 25.8, the median Gensini
      score was 7.5 (0-172), the mean FRS was 7.7 +/- 4.2, and the median FRS was 7 (0
      21). Correlation analysis revealed a significant relationship between FRS and
      Gensini score (r = 0.432, p < 0.0001). This relationship was confirmed by linear
      regression analysis (beta = 0.341, p < 0.0001). A cut-off level of 7.5 for FRS
      predicted severe CAD with a sensitivity of 68 % and a specificity of 73.6 % (ROC
      area under curve: 0.776, 95 % CI: 0.706-0.845, PPV: 78.1 %, NPV: 62.3 %, p <
      0.0001). CONCLUSION: Our work suggests that the FRS system is a simple and
      feasible method that can be used for prediction of CAD severity. As the sample
      size was small in our study, further large-scale studies are needed on this
      subject to draw solid conclusions.

PMID- 23873011
TI  - The dry season in haiti: a window of opportunity to eliminate cholera.
AB  - BACKGROUND: Since the beginning of the cholera epidemic in Haiti, attack rates
      have varied drastically with alternating peak and lull phases, which were partly
      associated with the fluctuating dry, rainy and cyclonic seasons. According to a
      study conducted in 2012, the toxigenic V. cholerae O1 strain responsible for the
      outbreak did not settle at a significant level in the Haitian aquatic
      environment. Therefore, we hypothesize that some areas of lingering cholera
      transmission during the dry season could play an important role in the re
      emergence of outbreaks during the rainy season. Our objective was therefore to
      describe the dynamics of cholera and assess the fight against the disease during
      the dry season. METHODS: A field study was conducted from February 19 to March
      29, 2013. After identifying the affected communes by analyzing the national
      cholera database, we visited corresponding health facilities to identify patient
      origins. We then conducted a field assessment of these foci to confirm the
      presence of cholera, assess factors associated with transmission and examine the
      activities implemented to control the epidemic since the beginning of the current
      dry season. RESULTS: We found that the great majority of Haitian communes
      (109/140) presented no sign of cholera transmission in February and March 2013.
      Suspected cases were concentrated in a small number of urban and rural areas,
      almost all of which were located in the northern half of the country and often in
      inland locales. In these areas, community health activities appeared insufficient
      and were often inappropriately targeted. Out of 49 analyzed foci, only 10 had
      benefited from at least one intervention involving the distribution of water
      treatment products together with an awareness campaign since December 2012.
      CONCLUSION: Cholera continues to affect Haiti as observed in early 2013; however,
      activities implemented to interrupt cholera transmission appear insufficient and
      poorly suited. This deficiency in the fight against cholera, especially at a
      period when transmission is weak, may explain the persistence of cholera even in
      the absence of significant aquatic reservoirs in Haiti.

PMID- 23873010
TI  - Clinical applications of musculoskeletal modelling for the shoulder and upper
      limb.
AB  - Musculoskeletal models have been developed to estimate internal loading on the
      human skeleton, which cannot directly be measured in vivo, from external
      measurements like kinematics and external forces. Such models of the shoulder and
      upper extremity have been used for a variety of purposes, ranging from
      understanding basic shoulder biomechanics to assisting in preoperative planning.
      In this review, we provide an overview of the most commonly used large-scale
      shoulder and upper extremity models and categorise the applications of these
      models according to the type of questions their users aimed to answer. We found
      that the most explored feature of a model is the possibility to predict the
      effect of a structural adaptation on functional outcome, for instance, to
      simulate a tendon transfer preoperatively. Recent studies have focused on
      minimising the mismatch in morphology between the model, often derived from
      cadaver studies, and the subject that is analysed. However, only a subset of the
      parameters that describe the model's geometry and, perhaps most importantly, the
      musculotendon properties can be obtained in vivo. Because most parameters are
      somehow interrelated, the others should be scaled to prevent inconsistencies in
      the model's structure, but it is not known exactly how. Although considerable
      effort is put into adding complexity to models, for example, by making them
      subject-specific, we have found little evidence of their superiority over current
      models. The current trend in development towards individualised, more complex
      models needs to be justified by demonstrating their ability to answer questions
      that cannot already be answered by existing models. 

PMID- 23873012
TI  - The role of defects in the reaction of chlorine atoms with alkanethiol self
      assembled monolayers.
AB  - Scanning tunneling microscopy (STM) in ultra-high-vacuum is used to investigate
      the reaction of gas-phase atomic chlorine with octanethiolate self-assembled
      monolayers on Au(111). Exposure to Cl atoms results in the formation of a variety
      of surface defects, and eventually leads to a complete loss of order within the
      alkanethiolate monolayer. X-ray photoelectron spectroscopy and thermal desorption
      mass spectrometry show that these morphological changes are accompanied by
      significant chlorination of the monolayer as well as a ~30% decrease in the
      amount of adsorbed sulfur. The rate of reaction is measured through the analysis
      of sequences of STM images, and coverage-vs.-exposure data shows that the average
      reactivity of any given molecule within the monolayer decreases as the reaction
      progresses. Working with the assumption that monolayer defects created by Cl-atom
      reaction will affect the reactivity of neighboring molecules, a kinetic Monte
      Carlo simulation shows the data are consistent with defect sites inhibiting
      reaction rate by a factor of 5 or more. This behavior is opposite to that found
      for hydrogen-atom reactions, where edge and defect sites were far more reactive.
      The dynamics of chlorine-atom reactivity are described primarily in terms of the
      formation and subsequent reaction of surface-adsorbed radicals, with surface
      defects providing sites where these radicals can be quenched.

PMID- 23873013
TI  - Clinical value of mesothelin in pleural effusions versus histology by medical
      thoracoscopy: brief report.
AB  - The aim of this study based on the third phase of the architecture of diagnostic
      research was to assess the sensitivity and specificity of soluble mesothelin
      related peptide (SMRP) in pleural exudative effusions (PE) compared to the
      histology obtained by medical thoracoscopy as the diagnostic gold standard
      examination. We assessed 104 consecutive thoracoscopies. SMRP concentrations were
      obtained using an ELISA test. We had 34 mesotheliomas (25 epithelioid and 9
      sarcomatoid), 35 pleural metastases, and 35 benign diseases. PE-SMRP were
      significantly higher in patients with epitheliomorphic mesothelioma (mean +/- SD
      46.55 +/- 44.29 nM) than in patients with sarcomatoid mesothelioma (16.11 +/-
      25.02 nM; p = 0.061), pleural metastasis (7.52 +/- 10.77 nM; p < 0.0001), or
      benign diseases (5.82 +/- 8.86 nM; p < 0.0001). Using ROC curve analysis, PE-SMRP
      offered an AUC of 0.767 in its ability to differentiate between patients with
      mesothelioma and all other diagnoses. The diagnostic sensitivity and specificity
      of PE-SMRP for distinguishing mesothelioma from all other causes of pleural
      effusion, at a cut-off value of 19.6 nM, were 58.8 and 97.1 %, respectively. PE
      SMRP higher than the assumed cut-off of 19.6 nM were observed in 18/25 (72.0%)
      epitheliomorphic mesotheliomas, 2/9 (22.2%) sarcomatoid mesotheliomas, 5/35
      (14.3%) pleural metastases, and 1/35 (2.9%) benign diseases. We conclude that PE
      SMRP adds some clinical information in the work-up of patients with a PE of
      unknown origin: (1) thoracoscopy should always be done in patients with a
      positive mesothelin; (2) a negative mesothelin does not exclude a malignant
      disease.

PMID- 23873014
TI  - Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype
      and antitumor cytotoxicity.
AB  - Substantial evidence indicates that cancer-associated fibroblasts (CAFs) are
      critical components in the process of cancer progression. However, the role of
      CAFs in the immunopathogenesis of human cancer remains elusive. In this study, we
      demonstrate that purified colorectal carcinoma-derived fibroblasts exhibit
      activated phenotypes characterized by substantial alpha-smooth muscle actin
      expression. These CAFs sharply suppress natural killer (NK) cell functions in co
      culture experiments. In contrast, normal skin fibroblasts had only a minimal
      effect on NK cell phenotype and function. Moreover, we demonstrated that
      prostaglandin E2 (PGE2) was released by fibroblasts in co-culture experiments.
      Thus, the functional modulation of NK cells by CAFs may represent a novel
      mechanism linking the pro-inflammatory response to immune tolerance within the
      tumor milieu. 

PMID- 23873015
TI  - Role of KAI1/CD82 polymorphisms in colon cancer risk in Han Chinese population.
AB  - The aim of this study is to investigate the associations between KAI1/CD82 gene
      polymorphisms and colorectal cancer (CRC)-risk predisposition. We undertook a
      case-control study to analyze two KAI1/CD82 polymorphisms (exon 3 -29166 C>T and
      exon 9 -52840 C>A) in an Han Chinese population, by extraction of genomic DNA
      from the peripheral blood of 356 patients with CRC and 378 control participants,
      and performed KAI1/CD82 genotyping using DNA sequencing. The obtained results
      indicated that overall, no statistically significant association was observed in
      exon 9 (-52840 C>A). Nevertheless, exon 3 (-29166 C>T) genotype was at increased
      risk of CRC (P = 0.006; odds ratio = 1.299, CI 95% 1.058-1.549). Furthermore, 
      29166 T allele CRCs were more significantly common in patients with tumor size of
      >4 cm than C allele CRC and in cases of poor differentiation and advanced
      pathological stage. These findings led us to conclude that polymorphism in exon 3
      (-29166 C>T) was observed to be associated with susceptibility of CRC. However,
      exon 9 (-52840 C>A) polymorphism showed no correlation to CRC susceptibility.
      Nevertheless, further investigation with a larger sample size is needed to
      support our results.

PMID- 23873016
TI  - Identifying oncological emergencies.
AB  - Prompt identification and treatment of life-threatening oncological conditions is
      of utmost importance and should always be included in the differential diagnosis.
      Oncological emergencies can have a myriad of presentations ranging from
      mechanical obstruction due to tumor growth to metabolic conditions due to
      abnormal secretions from the tumor. Notably, hematologic and infectious
      conditions may complicate the presentation of oncological emergencies. Advanced
      testing and imaging is generally required to recognize these serious
      presentations of common malignancies. Early diagnosis and treatment of these
      conditions can significantly affect the patient's clinical outcome. 

PMID- 23873017
TI  - New insight into the working mechanism of lithium-sulfur batteries: in situ and
      operando X-ray diffraction characterization.
AB  - In order to improve the electrochemical performances of lithium-sulfur batteries,
      it is crucial to understand profoundly their working mechanism and the limitation
      factors. This communication presents synchrotron-based in situ XRD studies of
      structural modifications occurring inside the cell upon cycling, since the active
      material changes constantly its form between solid and liquid phases. 

PMID- 23873018
TI  - Th1-mediated experimental autoimmune encephalomyelitis is CXCR3 independent.
AB  - Drugs that block leukocyte trafficking ameliorate multiple sclerosis (MS).
      Occurrences of opportunistic infection, however, highlight the need for novel
      drugs that modulate more restricted subsets of T cells. In this context,
      chemokines and their receptors are attractive therapeutic targets. CXCR3, a Th1
      associated chemokine receptor, is preferentially expressed on T cells that
      accumulate in MS lesions and central nervous system (CNS) infiltrates of mice
      with experimental autoimmune encephalomyelitis (EAE). Surprisingly, mice
      genetically deficient in either CXCR3 or CXCL10 succumb to EAE following active
      immunization with myelin antigens. EAE is mediated by a heterogeneous population
      of T cells in myelin-immunized mice. Hence, disease might develop in the absence
      of CXCR3 secondary to the compensatory action of encephalitogenic CCR6(+) Th17
      cells. However, in the current study, we show for the first time that blockade or
      genetic deficiency of either CXCR3 or of its primary ligand has no impact on
      clinical EAE induced by the adoptive transfer of highly polarized Th1 effector
      cells. Our data illustrate the fact that, although highly targeted
      immunotherapies might have more favorable side effect profiles, they are also
      more likely to be rendered ineffective by inherent redundancies in chemokine and
      cytokine networks that arise at sites of neuroinflammation. 

PMID- 23873019
TI  - Stabilization of alpha-helices by the self-assembly of macrocyclic peptides on
      the surface of gold nanoparticles for molecular recognition.
AB  - A novel strategy to stabilize the alpha-helical secondary structures of peptides
      upon binding to gold nanoparticles is described. Using a model protein-protein
      interaction system, we showed that AuNPs decorated with stabilized p53 alpha
      helix peptides can mediate specific molecular recognition with their target
      protein. 

PMID- 23873020
TI  - CMCTS stabilized Fe3O4 particles with extremely low toxicity as highly efficient
      near-infrared photothermal agents for in vivo tumor ablation.
AB  - With the potential uses of photothermal therapy (PTT) in cancer treatment with
      excellent efficacy, and the growing concerns about the nanotoxicity of
      hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the
      importance of searching for a biocompatible hyperthermia agent cannot be
      emphasized too much. In this work, a novel promising hyperthermia agent employing
      magnetic Fe3O4 particles with fairly low toxicity was proposed. This hyperthermia
      agent showed rapid heat generation under NIR irradiation. After modification with
      carboxymethyl chitosan (CMCTS), the obtained Fe3O4@CMCTS particles could disperse
      stably in PBS and serum without any aggregation. The modification of CMCTS could
      decrease the adsorption of bovine serum albumin (BSA) and improve the cellular
      uptake. In a comparative study with hollow gold nanospheres (HAuNS), Fe3O4@CMCTS
      particles exhibited a comparable photothermal effect and fairly low cytotoxicity.
      The in vivo magnetic resonance (MR) images of mice revealed that by attaching a
      magnet to the tumor, Fe3O4@CMCTS particles accumulated in the tumor after
      intravenous injection and showed a low distribution in the liver. After being
      exposed to a 808 nm laser for 5 min at a low power density of 1.5 W cm(-2), the
      tumors on Fe3O4@CMCTS-injected mice reached a temperature of ~52  degrees C and
      were completely destroyed. Thus, a kind of multifunctional magnetic nanoparticle
      with extremely low toxicity and a simple structure for simultaneous MR imaging,
      targeted drug delivery and photothermal therapy can be easily fabricated.

PMID- 23873021
TI  - Proximal predominance of small bowel injury associated with uncoated low-dose
      aspirin therapy: a video capsule study in chronic users.
AB  - BACKGROUND AND AIM: Only a limited number of studies have evaluated the small
      intestinal damage associated with chronic low-dose aspirin (LDA) therapy. We
      assessed, using capsule endoscopy, the prevalence and the characteristics of
      small bowel damage in chronic LDA users compared with patients taking an
      anticoagulant (AC) and those taking no antithrombotic drugs. PATIENTS AND
      METHODS: We retrospectively reviewed 75 capsule endoscopy recordings from three
      groups of patients with unexplained iron-deficient anemia: 28 patients receiving
      LDA, 15 receiving an AC, and 32 not receiving any antithrombotic drug. The
      severity and location of small intestinal mucosal breaks were assessed in a
      blinded manner by two endoscopists. RESULTS: All LDA users received uncoated
      aspirin. The number of small bowel mucosal breaks in patients receiving LDA
      (median 1, extremes 0-125) was significantly higher than that in those taking an
      AC (0, 0-1) (P=0.0005) or no antithrombotic drugs (0, 0-23) (P<0.0001). The
      prevalence of patients with mucosal breaks was higher in the LDA group (71.4%)
      than in the AC group (20%, P=0.001) and the control group (12.5%, P=0.000005).
      Mucosal breaks in LDA users were predominant in the first tertile of the small
      bowel. The difference between groups was significant only for mucosal breaks
      located in the first tertile (P<0.0001). CONCLUSION: About two-thirds of uncoated
      LDA chronic users with anemia have mucosal breaks in the small bowel. These
      lesions are predominant in the proximal part, suggesting a topical toxic effect
      of uncoated LDA.

PMID- 23873022
TI  - Testican-1-mediated epithelial-mesenchymal transition signaling confers acquired
      resistance to lapatinib in HER2-positive gastric cancer.
AB  - Human epidermal growth factor receptor 2 (HER2)-directed treatment using
      trastuzumab has shown clinical benefit in HER2-positive gastric cancer. Clinical
      trials using lapatinib in HER2-positive gastric cancer are also currently
      underway. As with other molecularly targeted agents, the emergence of acquired
      resistance to HER2-directed treatment is an imminent therapeutic problem for HER2
      positive gastric cancer. In order to investigate the mechanisms of acquired
      resistance to HER2-directed treatment in gastric cancer, we generated lapatinib
      resistant gastric cancer cell lines (SNU216 LR) in vitro by chronic exposure of a
      HER2-positive gastric cancer cell line (SNU216) to lapatinib. The resultant
      SNU216 LR cells were also resistant to gefitinib, cetuximab, trastuzumab,
      afatinib and dacomitinib. Interestingly, SNU216 LR cells displayed an epithelial
      mesenchymal transition (EMT) phenotype and maintained the activation of MET,
      HER3, Stat3, Akt and mitogen-activated protein kinase signaling in the presence
      of lapatinib. Using gene expression arrays, we identified the upregulation of a
      variety of EMT-related genes and extracellular matrix molecules, such as Testican
      1, in SNU216 LR cells. We showed that the inhibition of Testican-1 by small
      interfering RNA decreased Testican-1-induced, MET-dependent, downstream
      signaling, and restored sensitivity to lapatinib in these cells. Furthermore,
      treatment with XAV939 selectively inhibited beta-catenin-mediated transcription
      and Testican-1-induced EMT signaling, leading to G1 arrest. Taken together, these
      data support the potential role of EMT in acquired resistance to HER2-directed
      treatment in HER2-positive gastric cancer, and provide insights into strategies
      for preventing and/or overcoming this resistance in patients. 

PMID- 23873023
TI  - Fbw7-dependent cyclin E regulation ensures terminal maturation of bone marrow
      erythroid cells by restraining oxidative metabolism.
AB  - The mechanisms that coordinate the final mitotic divisions of terminally
      differentiated bone marrow (BM) erythroid cells with components of their
      structural and functional maturation program remain largely undefined. We
      previously identified phenotypes resembling those found in early-stage
      myelodysplastic syndromes (MDS), including ineffective erythropoiesis,
      morphologic dysplasia and BM hyper-cellularity, in a knock-in mouse model in
      which cyclin E mutations were introduced at its two Cdc4 phosphodegrons (CPDs) to
      ablate Fbw7-dependent ubiquitination and degradation. Here, we have examined the
      physiologic consequences of cyclin E dysregulation in BM erythroid cells during
      terminal maturation in vivo. We found that cyclin E protein levels in BM
      erythroid cells are dynamically regulated in a CPD-dependent manner and that
      disruption of Fbw7-dependent cyclin E regulation impairs terminal erythroid cell
      maturation at a discrete stage before enucleation. At this stage of erythroid
      cell maturation, CPD phosphorylation of cyclin E regulates both cell-cycle arrest
      and survival. We also found that normal regulation of cyclin E restrains
      mitochondrial reactive oxygen species (ROS) accumulation and expression of genes
      that promote mitochondrial biogenesis and oxidative metabolism during terminal
      erythroid maturation. In the setting of dysregulated cyclin E expression, p53 is
      activated in BM erythroid cells as part of a DNA damage response-type pathway,
      which mitigates ineffective erythropoiesis, in contrast to the role of p53
      induction in other models of dyserythropoiesis. Finally, cyclin E dysregulation
      and ROS accumulation induce histone H3 lysine 9 hyper-methylation and disrupt
      components of the normal terminal erythroid maturation gene expression program.
      Thus, ubiquitin-proteasome pathway control of G1-to-S-phase progression is
      intrinsically linked to regulation of metabolism and gene expression in
      terminally differentiating BM erythroid cells. 

PMID- 23873025
TI  - CD82/KAI expression prevents IL-8-mediated endothelial gap formation in late
      stage melanomas.
AB  - Melanoma cells facilitate endothelial gap formation, the first step during tumor
      transendothelial migration, which is mediated by both adhesion and endogenously
      produced chemokines (in particular, interleukin-8 (IL-8)). Tetraspanins are
      localized to the cell surface in cancer and participate in various functions
      including invasion of tissues mediated by secretion of cytokines and matrix
      metalloproteinases. However, little is known about the role of CD82 tetraspanins
      in malignant melanomas during cancer cell invasion. In this study, we
      investigated the functional importance of CD82 expression in melanoma-mediated
      gap formation by using cDNAs to induce CD82 expression in highly invasive
      melanoma cell lines. Results showed that CD82 expression inhibited melanoma cell
      induced gap formation, melanoma cell extravasation in vitro and subsequent lung
      metastasis development in vivo. Mechanistic studies showed that inducible
      expression of CD82 in highly metastatic melanoma cells significantly increased
      p21 expression upon binding of Duffy antigen receptor group (DARC), inducing
      tumor cell senescence and interrupting IL-8-mediated vascular endothelial (VE)
      cadherin disassembly. Taken together, these studies provide a rationale for using
      drug therapies that restore CD82 expression and inhibit IL-8 production to
      inhibit late-stage melanoma cell extravasation and subsequent metastasis
      development.

PMID- 23873024
TI  - Prolactin cooperates with loss of p53 to promote claudin-low mammary carcinomas.
AB  - TP53 is one of the most commonly mutated genes in cancer. In breast cancer, it is
      mutated in about 40% of primary clinical tumors and is associated with poor
      survival. The mammotrophic hormone, prolactin (PRL), and/or its receptor are also
      expressed in many breast cancers, and accumulating epidemiologic data link PRL to
      breast cancer development and progression. Like TP53 mutations, evidence for PRL
      activity is evident across several molecular cancer subtypes, and elevated PRL
      expression and loss of p53 have been observed in some of the same clinical
      tumors. In order to examine the interaction of these factors, we used genetically
      modified mouse models of mammary-specific p53 loss and local overexpression of
      PRL. We demonstrated that mammary PRL decreased the latency of tumors in the
      absence of p53, and increased the proportion of triple-negative claudin-low
      carcinomas, which display similarities to human clinical metaplastic carcinomas.
      Moreover, PRL/p53(-/-) carcinomas displayed higher rates of proliferation and
      more aggressive behavior. Transcripts associated with cell cycle progression,
      invasion and stromal reactivity were differentially expressed in carcinomas that
      developed in the presence of elevated PRL. PRL/p53(-/-) carcinomas also exhibited
      selectively altered expression of activating protein-1 components, including
      higher levels of c-Jun and FosL1, which can drive transcription of many of these
      genes and the epithelial-mesenchymal transition. The ability of PRL to promote
      claudin-low carcinomas demonstrates that PRL can influence this subset of triple
      negative breast cancers, which may have been obscured by the relative infrequency
      of this cancer subtype. Our findings suggest novel therapeutic approaches, and
      provide a preclinical model to develop possible agents.

PMID- 23873026
TI  - Prdm5 suppresses Apc(Min)-driven intestinal adenomas and regulates
      monoacylglycerol lipase expression.
AB  - PRDM proteins are tissue-specific transcription factors often deregulated in
      diseases, particularly in cancer where different members have been found to act
      as oncogenes or tumor suppressors. PRDM5 is a poorly characterized member of the
      PRDM family for which several studies have reported a high frequency of promoter
      hypermethylation in cancer types of gastrointestinal origin. We report here the
      characterization of Prdm5 knockout mice in the context of intestinal
      carcinogenesis. We demonstrate that loss of Prdm5 increases the number of
      adenomas throughout the murine small intestine on an Apc(Min) background. By
      using the genome-wide ChIP-seq (chromatin immunoprecipitation (ChIP) followed by
      DNA sequencing) and transcriptome analyses we identify loci encoding proteins
      involved in metabolic processes as prominent PRDM5 targets and characterize
      monoacylglycerol lipase (Mgll) as a direct PRDM5 target in human colon cancer
      cells and in Prdm5 mutant mouse intestines. Moreover, we report the
      downregulation of PRDM5 protein expression in human colon neoplastic lesions. In
      summary, our data provide the first causal link between Prdm5 loss and intestinal
      carcinogenesis, and uncover an extensive and novel PRDM5 target repertoire likely
      facilitating the tumor-suppressive functions of PRDM5. 

PMID- 23873027
TI  - Androgen receptor (AR) differential roles in hormone-related tumors including
      prostate, bladder, kidney, lung, breast and liver.
AB  - The androgen receptor (AR) is expressed in many cell types and the androgen/AR
      signaling has been found to have important roles in modulating tumorigenesis and
      metastasis in several cancers including prostate, bladder, kidney, lung, breast
      and liver. However, whether AR has differential roles in the individual cells
      within these tumors that contain a variety of cell types remains unclear.
      Generation of AR knockout (ARKO) mouse models with deletion of AR in selective
      cells within tumors indeed have uncovered many unique AR roles in the individual
      cell types during cancer development and progression. This review will discuss
      the results obtained from various ARKO mice and different human cell lines with
      special attention to the cell type- and tissue-specific ARKO models. The
      understanding of various results showing the AR indeed has distinct and
      contrasting roles in each cell type within many hormone-related tumors (as
      stimulator in bladder, kidney and lung metastases vs as suppressor in prostate
      and liver metastases) may eventually help us to develop better therapeutic
      approaches by targeting the AR or its downstream signaling in individual cell
      types to better battle these hormone-related tumors in different stages. 

PMID- 23873028
TI  - FER kinase promotes breast cancer metastasis by regulating alpha6- and beta1
      integrin-dependent cell adhesion and anoikis resistance.
AB  - Metastatic breast cancer cannot be treated successfully. Currently, the targeted
      therapies for metastatic disease are limited to human epidermal growth factor
      receptor 2 and hormone receptor antagonists. Understanding the mechanisms of
      breast cancer growth and metastasis is therefore crucial for the development of
      new intervention strategies. Here, we show that FER kinase (FER) controls
      migration and metastasis of invasive human breast cancer cell lines by regulating
      alpha6- and beta1-integrin-dependent adhesion. Conversely, the overexpression of
      FER in non-metastatic breast cancer cells induces pro-invasive features. FER
      drives anoikis resistance, regulates tumour growth and is necessary for
      metastasis in a mouse model of human breast cancer. In human invasive breast
      cancer, high FER expression is an independent prognostic factor that correlates
      with high-grade basal/triple-negative tumours and worse overall survival,
      especially in lymph node-negative patients. These findings establish FER as a
      promising target for the prevention and inhibition of metastatic breast cancer. 

PMID- 23873029
TI  - Functions of TAp63 and p53 in restraining the development of metastatic cancer.
AB  - Many tumours harbour mutations in the p53 tumour-suppressor gene that result in
      the expression of a mutant p53 protein. This mutant p53 protein has, in most
      cases, lost wild-type transcriptional activity and can also acquire novel
      functions in promoting invasion and metastasis. One of the mechanisms underlying
      these novel functions involves the ability of the mutant p53 to interfere with
      other transcription factors, including the p53 family protein TAp63. To
      investigate whether simultaneous depletion of both p53 and TAp63 can recapitulate
      the effect of mutant p53 expression in vivo, we used a mouse model of pancreatic
      cancer in which the expression of mutant p53 resulted in the rapid appearance of
      primary tumours and metastases. As shown previously, loss of one allele of wild
      type (WT) p53 accelerated tumour development. A change of one WT p53 allele into
      mutant p53 did not further accelerate tumour development, but did promote the
      formation of metastasis. By contrast, loss of TAp63 did not significantly
      accelerate tumour development or metastasis. However, simultaneous depletion of
      p53 and TAp63 led to both rapid tumour development and metastatic potential,
      although the incidence of metastases remained lower than that seen in mutant p53
      expressing tumours. TAp63/p53-null cells derived from these mice also showed an
      enhanced ability to scatter and invade in tissue culture as was observed in
      mutant p53 cells. These data suggest that depletion of TAp63 in a p53-null tumour
      can promote metastasis and recapitulate-to some extent-the consequences of mutant
      p53 expression. 

PMID- 23873031
TI  - Sphingosine kinase 1 enables communication between melanoma cells and fibroblasts
      that provides a new link to metastasis.
AB  - In this issue of Oncogene, Albinet et al. have demonstrated a critical role of
      melanoma sphingosine kinase 1, which catalyses formation of sphingosine 1
      phosphate (S1P), in promoting the differentiation of fibroblasts into
      myofibroblasts. The myofibroblast sphingosine kinase 1 then promotes the S1P
      dependent dissemination (metastasis) of melanoma cells via a S1P receptor 3
      mediated mechanism. These findings are of major significance because they provide
      a novel mechanism of interaction between melanoma and the microenvironment niche
      in promoting metastasis. These studies therefore identify S1P derived from
      myofibroblasts and melanoma cells as a novel target for therapeutic intervention.

PMID- 23873030
TI  - Mutations that disrupt PHOXB interaction with the neuronal calcium sensor HPCAL1
      impede cellular differentiation in neuroblastoma.
AB  - Heterozygous germline mutations in PHOX2B, a transcriptional regulator of
      sympathetic neuronal differentiation, predispose to diseases of the sympathetic
      nervous system, including neuroblastoma and congenital central hypoventilation
      syndrome (CCHS). Although the PHOX2B variants in CCHS largely involve expansions
      of the second polyalanine repeat within the C-terminus of the protein, those
      associated with neuroblastic tumors are nearly always frameshift and truncation
      mutations. To test the hypothesis that the neuroblastoma-associated variants
      exert their effects through loss or gain of protein-protein interactions, we
      performed a large-scale yeast two-hybrid screen using both wild-type (WT) and six
      different mutant PHOX2B proteins against over 10 000 human genes. The neuronal
      calcium sensor protein HPCAL1 (VILIP-3) exhibited strong binding to WT PHOX2B and
      a CCHS-associated polyalanine expansion mutant but only weakly or not at all to
      neuroblastoma-associated frameshift and truncation variants. We demonstrate that
      both WT PHOX2B and the neuroblastoma-associated R100L missense and the CCHS
      associated alanine expansion variants induce nuclear translocation of HPCAL1 in a
      Ca(2+)-independent manner, while the neuroblastoma-associated 676delG frameshift
      and K155X truncation mutants impair subcellular localization of HPCAL1, causing
      it to remain in the cytoplasm. HPCAL1 did not appreciably influence the ability
      of WT PHOX2B to transactivate the DBH promoter, nor did it alter the decreased
      transactivation potential of PHOX2B variants in 293T cells. Abrogation of the
      PHOX2B-HPCAL1 interaction by shRNA knockdown of HPCAL1 in neuroblastoma cells
      expressing PHOX2B led to impaired neurite outgrowth with transcriptional profiles
      indicative of inhibited sympathetic neuronal differentiation. Our results suggest
      that certain PHOX2B variants associated with neuroblastoma pathogenesis, because
      of their inability to bind to key interacting proteins such as HPCAL1, may
      predispose to this malignancy by impeding the differentiation of immature
      sympathetic neurons. 

PMID- 23873032
TI  - Clinical characteristics of papillary thyroid microcarcinoma less than or equal
      to 5 mm on ultrasonography.
AB  - Management of papillary thyroid microcarcinoma sized <=5 mm identified on
      ultrasonography is controversial. In this study, we evaluated the clinical
      characteristics of papillary thyroid microcarcinoma sized <=5 mm on
      ultrasonography in comparison to those >5 mm and sought to present rationales for
      optimal management in papillary thyroid microcarcinoma <=5 mm. The medical
      records of 396 patients who underwent surgery for papillary thyroid carcinoma
      between 2009 and 2011 were retrospectively analyzed. The patients were grouped
      into A (<=5 mm, n = 132) or B (>5 mm, n = 264) and the clinicopathologic
      characteristics of the patients were reviewed and compared between the two
      groups. Tumor capsular invasion (45.5 vs. 59.8 %, p = 0.007) and cervical lymph
      node metastasis (18.2 vs. 29.2 %, p = 0.018) were more frequent in group B.
      Nonetheless, group A presented lymph node metastasis in 42.3 % of multifocal
      cases showing no difference to that of group B (41.5 %, p = 0.946) and also
      included five cases (3.8 %) of lateral neck metastasis. Multifocality was the
      only predictive factor for lymph node metastasis in group A (p < 0.001). Over
      half (55.3 %) of the patients of group A were diagnosed with papillary carcinoma
      in private clinics; however, only 5.5 % of these patients underwent assessment of
      lateral neck lymph nodes initially. In conclusion, higher risk of cervical lymph
      node metastasis should be considered in evaluation and surgical decision of
      papillary thyroid microcarcinoma <=5 mm identified on ultrasonography with
      multifocality. Evaluation of the cervical lymph nodes including the lateral neck
      should not be overlooked when suspicious thyroid nodule suggesting malignancy
      sized <=5 mm shows multifocal lesions. 

PMID- 23873034
TI  - Quality assessment of ophthalmic questionnaires: review and recommendations.
AB  - PURPOSE: The aim of this article was to systematically review all the available
      ophthalmic patient-reported outcome (PRO) instruments (questionnaires) that
      demonstrated interval measurement properties to identify the instruments with the
      highest psychometric quality for use in different eye diseases and conditions.
      METHODS: An extensive literature review was carried out to identify all existing
      ophthalmic PRO instruments. Instruments were then excluded if they did not have
      demonstrable interval measurement properties; the remaining instruments were
      reviewed. The quality of the following psychometric properties was assessed:
      content development (initial item development process), performance of the
      response scale, dimensionality (whether the instrument measures a single
      construct), measurement precision, validity (convergent, concurrent,
      discriminant, and known groups), reliability (test-retest), targeting (whether
      the items are appropriate [e.g., difficulty level] for the population),
      differential item functioning (whether subgroups of people respond differently to
      an item), and responsiveness. RESULTS: The search identified 48 PRO instruments
      that demonstrated interval measurement properties, and these were relevant to
      nine applications: glaucoma, dry eye, refractive errors, cataract, amblyopia and
      strabismus, macular diseases, adult low vision, children low vision, and others.
      These instruments were evaluated against the psychometric property quality
      criteria and were rated for quality based on the number of criteria met.
      CONCLUSIONS: This review provides a descriptive catalog of ophthalmic PRO
      instruments to inform researchers and clinicians on the choice of the highest
      quality PRO instrument suitable for their purpose.

PMID- 23873033
TI  - Glaucoma medication adherence among African Americans: program development.
AB  - PURPOSE: To elucidate barriers and facilitators related to glaucoma medication
      adherence among African Americans (AA) with glaucoma and to elicit input from a
      community-based participatory research team to guide the development of a
      culturally informed health promotion program for improving glaucoma medication
      adherence among AAs. METHODS: The nominal group technique (NGT), a highly
      structured focus group methodology, was implemented with 12 separate groups of AA
      patients with glaucoma (N = 89) to identify barriers and facilitators related to
      glaucoma medication usage. Participant rank-ordering votes were summed across
      groups and categorized into themes. Next, an individually and culturally targeted
      health promotion program promoting appropriate medication adherence was developed
      based on focus group results and input from a community-based participatory
      research team. RESULTS: The top five barriers included problems with
      forgetfulness, side effects, cost/affordability, eyedrop administration, and the
      eyedrop schedule. The most salient top five facilitators were fear or thoughts
      about the consequences of not taking eyedrops; use of memory aids, cues, or
      strategies; maintaining a regular routine or schedule for eyedrop administration;
      ability to afford eyedrops; and keeping eyedrops in the same area. The resulting
      health promotion program was based on a multicomponent empowerment framework that
      included glaucoma education, motivational interviewing, and problem-solving
      training to improve glaucoma medication adherence. CONCLUSIONS: Barriers and
      facilitators related to glaucoma medication adherence among AAs are
      multifactorial. Based on the NGT themes and input from the community-based
      participatory research team, a culturally informed health promotion program was
      designed and holds great promise for improving medication adherence among this
      vulnerable population.

PMID- 23873035
TI  - Interpretation of low-vision rehabilitation outcome measures.
AB  - PURPOSE: This article presents a theoretical interpretation of patient-reported
      outcomes of low-vision rehabilitation (LVR) using rating scale questionnaires and
      uses previously published results of LVR outcome studies to illustrate
      theoretical points and validate assumptions. THEORY: Patients' judgments of the
      difficulty they have performing tasks are interpreted as magnitude estimates of
      their functional reserve for each task, which is the difference between their
      visual ability and the visual ability demanded by the task. We assume that
      improvements in functional reserve can occur by increasing the patient's visual
      ability with medical, surgical, or refractive interventions or decreasing the
      visual ability demanded by the item with activity-specific vision assistive
      equipment, adaptations, and environmental modifications. Activity-specific
      interventions cause differential item functioning (intervention-related DIF).
      Intervention-related DIF makes the measured size of the treatment effect
      dependent on the item content and the mix of responsive and unresponsive items to
      intervention. CONCLUSIONS: Because intervention-related DIF depends on the choice
      of items, the outcome measure selected should be appropriate to the aims of the
      intervention and the impairment level of the sample to demonstrate the full
      effects of an intervention. Items that are given extreme positive ratings at
      preintervention baseline (e.g., "not difficult") have no room for improvement.
      These items must also be filtered out because they will dilute the measured
      effect of the activity-specific interventions of LVR.

PMID- 23873037
TI  - Quality indicators for multidisciplinary team functioning in community-based
      children's mental health services.
AB  - The current study examined the organizational social context in 21 community
      based programs serving youth at-risk for out-of-home care due to emotional or
      behavioral disorders and their families and program performance on five quality
      indicators of team functioning in teams that included a family support
      specialist. Results indicate that programs with higher performance on structures
      to facilitate teamwork, informal communication mechanisms among team members, and
      the ability to integrate family support specialists as equal members of the team
      showed more positive organizational functioning. Implications for the role of
      quality indicators in health care reform efforts are discussed. 

PMID- 23873038
TI  - Measuring perceived rehabilitation needs of people with schizophrenia in mainland
      China.
AB  - This paper reports the development and validation of the Wuxi version of the
      Rehabilitation Needs Questionnaire for People with Schizophrenia (PRNQ-S-WX)
      based on the original Hong Kong version. PRNQ-S-WX was validated by exploratory
      factor analysis (EFA) using a convenience sample of 250 people with
      schizophrenia. EFA yielded a 17-factor solution accounting for 81.3 % of the
      total variance which resulted in a 75-item PRNQ-S-WX. The questionnaire has sound
      internal consistencies. Its factor structure is similar to the Hong Kong version.
      Some suggestions for policy, service and research development in mental health in
      mainland China are made. 

PMID- 23873036
TI  - Comparison of clinician-predicted to measured low vision outcomes.
AB  - PURPOSE: To compare low-vision rehabilitation (LVR) clinicians' predictions of
      the probability of success of LVR with patients' self-reported outcomes after
      provision of usual outpatient LVR services and to determine if patients' traits
      influence clinician ratings. METHODS: The Activity Inventory (AI), a self-report
      visual function questionnaire, was administered pre-and post-LVR to 316 low
      vision patients served by 28 LVR centers that participated in a collaborative
      observational study. The physical component of the Short Form-36, Geriatric
      Depression Scale, and Telephone Interview for Cognitive Status were also
      administered pre-LVR to measure physical capability, depression, and cognitive
      status. After patient evaluation, 38 LVR clinicians estimated the probability of
      outcome success (POS) using their own criteria. The POS ratings and change in
      functional ability were used to assess the effects of patients' baseline traits
      on predicted outcomes. RESULTS: A regression analysis with a hierarchical random
      effects model showed no relationship between LVR physician POS estimates and AI
      based outcomes. In another analysis, kappa statistics were calculated to
      determine the probability of agreement between POS and AI-based outcomes for
      different outcome criteria. Across all comparisons, none of the kappa values were
      significantly different from 0, which indicates that the rate of agreement is
      equivalent to chance. In an exploratory analysis, hierarchical mixed-effects
      regression models show that POS ratings are associated with information about the
      patient's cognitive functioning and the combination of visual acuity and
      functional ability, as opposed to visual acuity or functional ability alone.
      CONCLUSIONS: Clinicians' predictions of LVR outcomes seem to be influenced by
      knowledge of patients' cognitive functioning and the combination of visual acuity
      and functional ability-information clinicians acquire from the patient's history
      and examination. However, clinicians' predictions do not agree with observed
      changes in functional ability from the patient's perspective; they are no better
      than chance.

PMID- 23873039
TI  - Pervasive genetic hitchhiking and clonal interference in forty evolving yeast
      populations.
AB  - The dynamics of adaptation determine which mutations fix in a population, and
      hence how reproducible evolution will be. This is central to understanding the
      spectra of mutations recovered in the evolution of antibiotic resistance, the
      response of pathogens to immune selection, and the dynamics of cancer
      progression. In laboratory evolution experiments, demonstrably beneficial
      mutations are found repeatedly, but are often accompanied by other mutations with
      no obvious benefit. Here we use whole-genome whole-population sequencing to
      examine the dynamics of genome sequence evolution at high temporal resolution in
      40 replicate Saccharomyces cerevisiae populations growing in rich medium for
      1,000 generations. We find pervasive genetic hitchhiking: multiple mutations
      arise and move synchronously through the population as mutational 'cohorts'.
      Multiple clonal cohorts are often present simultaneously, competing with each
      other in the same population. Our results show that patterns of sequence
      evolution are driven by a balance between these chance effects of hitchhiking and
      interference, which increase stochastic variation in evolutionary outcomes, and
      the deterministic action of selection on individual mutations, which favours
      parallel evolutionary solutions in replicate populations. 

PMID- 23873040
TI  - Coordination of heart and lung co-development by a multipotent cardiopulmonary
      progenitor.
AB  - Co-development of the cardiovascular and pulmonary systems is a recent
      evolutionary adaption to terrestrial life that couples cardiac output with the
      gas exchange function of the lung. Here we show that the murine pulmonary
      vasculature develops even in the absence of lung development. We have identified
      a population of multipotent cardiopulmonary mesoderm progenitors (CPPs) within
      the posterior pole of the heart that are marked by the expression of Wnt2, Gli1
      and Isl1. We show that CPPs arise from cardiac progenitors before lung
      development. Lineage tracing and clonal analysis demonstrates that CPPs generate
      the mesoderm lineages within the cardiac inflow tract and lung including
      cardiomyocytes, pulmonary vascular and airway smooth muscle, proximal vascular
      endothelium, and pericyte-like cells. CPPs are regulated by hedgehog expression
      from the foregut endoderm, which is required for connection of the pulmonary
      vasculature to the heart. Together, these studies identify a novel population of
      multipotent cardiopulmonary progenitors that coordinates heart and lung co
      development that is required for adaptation to terrestrial existence. 

PMID- 23873041
TI  - Epithelial junctions maintain tissue architecture by directing planar spindle
      orientation.
AB  - During epithelial cell proliferation, planar alignment of the mitotic spindle
      coordinates the local process of symmetric cell cleavage with the global
      maintenance of polarized tissue architecture. Although the disruption of planar
      spindle alignment is proposed to cause epithelial to mesenchymal transition and
      cancer, the in vivo mechanisms regulating mitotic spindle orientation remain
      elusive. Here we demonstrate that the actomyosin cortex and the junction
      localized neoplastic tumour suppressors Scribbled and Discs large 1 have
      essential roles in planar spindle alignment and thus the control of epithelial
      integrity in the Drosophila imaginal disc. We show that defective alignment of
      the mitotic spindle correlates with cell delamination and apoptotic death, and
      that blocking the death of misaligned cells is sufficient to drive the formation
      of basally localized tumour-like masses. These findings indicate a key role for
      junction-mediated spindle alignment in the maintenance of epithelial integrity,
      and also reveal a previously unknown cell-death-mediated tumour-suppressor
      function inherent in the polarized architecture of epithelia. 

PMID- 23873042
TI  - The initiation of mammalian protein synthesis and mRNA scanning mechanism.
AB  - During translation initiation in eukaryotes, the small ribosomal subunit binds
      messenger RNA at the 5' end and scans in the 5' to 3' direction to locate the
      initiation codon, form the 80S initiation complex and start protein synthesis.
      This simple, yet intricate, process is guided by multiple initiation factors.
      Here we determine the structures of three complexes of the small ribosomal
      subunit that represent distinct steps in mammalian translation initiation. These
      structures reveal the locations of eIF1, eIF1A, mRNA and initiator transfer RNA
      bound to the small ribosomal subunit and provide insights into the details of
      translation initiation specific to eukaryotes. Conformational changes associated
      with the captured functional states reveal the dynamics of the interactions in
      the P site of the ribosome. These results have functional implications for the
      mechanism of mRNA scanning. 

PMID- 23873043
TI  - Genomic evidence for ameiotic evolution in the bdelloid rotifer Adineta vaga.
AB  - Loss of sexual reproduction is considered an evolutionary dead end for metazoans,
      but bdelloid rotifers challenge this view as they appear to have persisted
      asexually for millions of years. Neither male sex organs nor meiosis have ever
      been observed in these microscopic animals: oocytes are formed through mitotic
      divisions, with no reduction of chromosome number and no indication of chromosome
      pairing. However, current evidence does not exclude that they may engage in sex
      on rare, cryptic occasions. Here we report the genome of a bdelloid rotifer,
      Adineta vaga (Davis, 1873), and show that its structure is incompatible with
      conventional meiosis. At gene scale, the genome of A. vaga is tetraploid and
      comprises both anciently duplicated segments and less divergent allelic regions.
      However, in contrast to sexual species, the allelic regions are rearranged and
      sometimes even found on the same chromosome. Such structure does not allow
      meiotic pairing; instead, we find abundant evidence of gene conversion, which may
      limit the accumulation of deleterious mutations in the absence of meiosis. Gene
      families involved in resistance to oxidation, carbohydrate metabolism and defence
      against transposons are significantly expanded, which may explain why
      transposable elements cover only 3% of the assembled sequence. Furthermore, 8% of
      the genes are likely to be of non-metazoan origin and were probably acquired
      horizontally. This apparent convergence between bdelloids and prokaryotes sheds
      new light on the evolutionary significance of sex. 

PMID- 23873046
TI  - Effectiveness of deslorelin acetate subcutaneous implantation in a domestic queen
      with after-spaying urinary incontinence.
AB  - A 2-year-old female ovariectomised Norwegian Forest cat with a history of post
      spaying urinary incontinence was diagnosed with acquired urinary sphincter
      mechanism incompetence (USMI) after complete clinical and laboratory examination.
      Although there is no literature regarding the treatment of post-spaying USMI in
      cats, deslorelin acetate is successful in the treatment of post-spaying USMI in
      dogs. Deslorelin acetate implants have been shown previously to be effective for
      contraception and oestrus suppression in queens, and suppression of reproductive
      function in tomcats. Therefore, deslorelin acetate implant treatment was chosen
      for treatment of post-spaying USMI in this queen. Follow-up examinations were
      performed on days 8, 15 and 30 after deslorelin implant insertion. Urinary
      continence was restored about 25 days after implantation and maintained for at
      least 15 months, without treatment-related negative effects. In the present case
      report, the post-spaying urinary incontinence related to the acquired USMI was
      successfully treated with a deslorelin acetate implant. In addition, safe
      implantation was easy in cats and the single injection resulted in long-lasting
      efficacy. Further studies are needed to confirm the usefulness of deslorelin
      acetate treatment for post-spaying USMI in queens and to better delineate the
      duration of efficacy. 

PMID- 23873045
TI  - MYBPC1 mutations impair skeletal muscle function in zebrafish models of
      arthrogryposis.
AB  - Myosin-binding protein C1 (MYBPC1) is an abundant skeletal muscle protein that is
      expressed predominantly in slow-twitch muscle fibers. Human MYBPC1 mutations are
      associated with distal arthrogryposis type 1 and lethal congenital contracture
      syndrome type 4. As MYBPC1 function is incompletely understood, the mechanism by
      which human mutations result in contractures is unknown. Here, we demonstrate
      using antisense morpholino knockdown, that mybpc1 is required for embryonic motor
      activity and survival in a zebrafish model of arthrogryposis. Mybpc1 morphant
      embryos have severe body curvature, cardiac edema, impaired motor excitation and
      are delayed in hatching. Myofibril organization is selectively impaired in slow
      skeletal muscle and sarcomere numbers are greatly reduced in mybpc1 knockdown
      embryos, although electron microscopy reveals normal sarcomere structure. To
      evaluate the effects of human distal arthrogryposis mutations, mybpc1 mRNAs
      containing the corresponding human W236R and Y856H MYBPC1 mutations were injected
      into embryos. Dominant-negative effects of these mutations were suggested by the
      resultant mild bent body curvature, decreased motor activity, as well as impaired
      overall survival compared with overexpression of wild-type RNA. These results
      demonstrate a critical role for mybpc1 in slow skeletal muscle development and
      establish zebrafish as a tractable model of human distal arthrogryposis. 

PMID- 23873047
TI  - Case series of feline panleukopenia virus in an animal shelter.
AB  - The aim of this study was to describe a series of confirmed and suspected cases
      of feline panleukopenia virus (FPV) and in-contact cats in an adoption-guarantee
      shelter in an FPV-endemic area by reviewing shelter records over a 10-month
      period (January-October 2010). Cats were divided into three groups: in-contact
      group - asymptomatic cats that were housed with a FPV fecal antigen (Ag)-positive
      cat/kitten as part of a litter group (n = 66); FPV-survivors group (FPV-infected
      survivors) - tested FPV fecal Ag-positive and showed clinical signs of FPV, but
      survived (n = 27); FPV-non-survivors group (FPV-infected non-survivors) - showed
      clinical signs of FPV and either tested FPV fecal Ag-positive or were housed with
      an Ag-positive family member, but did not survive (n = 52). Ages ranged from 3
      weeks to 3 years, but most were <6 months old (in-contact group: 79%; FPV
      survivors group: 70%; FPV-non-survivors group: 85%). A seasonal peak occurred
      over summer, but cases occurred year-round. Anorexia, dehydration, fever and
      diarrhea predominated in the FPV-survivors group, and death was preceded by
      clinical signs of circulatory shock in the FPV-non-survivors group. Housing
      litters of kittens with their mother was not associated with improved outcome,
      perhaps because in this population clinical FPV infection was relatively common
      in queens arriving at the shelter with susceptible litters. 

PMID- 23873044
TI  - Genetic influences on plasma CFH and CFHR1 concentrations and their role in
      susceptibility to age-related macular degeneration.
AB  - It is a longstanding puzzle why non-coding variants in the complement factor H
      (CFH) gene are more strongly associated with age-related macular degeneration
      (AMD) than functional coding variants that directly influence the alternative
      complement pathway. The situation is complicated by tight genetic associations
      across the region, including the adjacent CFH-related genes CFHR3 and CFHR1,
      which may themselves influence the alternative complement pathway and are
      contained within a common deletion (CNP147) which is associated with protection
      against AMD. It is unclear whether this association is mediated through a
      protective effect of low plasma CFHR1 concentrations, high plasma CFH or both. We
      examined the triangular relationships of CFH/CFHR3/CFHR1 genotype, plasma CFH or
      CFHR1 concentrations and AMD susceptibility in combined case-control (1256 cases,
      1020 controls) and cross-sectional population (n = 1004) studies and carried out
      genome-wide association studies of plasma CFH and CFHR1 concentrations. A non
      coding CFH SNP (rs6677604) and the CNP147 deletion were strongly correlated both
      with each other and with plasma CFH and CFHR1 concentrations. The plasma CFH
      raising rs6677604 allele and raised plasma CFH concentration were each associated
      with AMD protection. In contrast, the protective association of the CNP147
      deletion with AMD was not mediated by low plasma CFHR1, since AMD-free controls
      showed increased plasma CFHR1 compared with cases, but it may be mediated by the
      association of CNP147 with raised plasma CFH concentration. The results are most
      consistent with a regulatory locus within a 32 kb region of the CFH gene, with a
      major effect on plasma CFH concentration and AMD susceptibility. 

PMID- 23873049
TI  - Pd-catalyzed addition of boronic acids to ynol ethers: a highly regio- and
      stereoselective synthesis of trisubstituted vinyl ethers.
AB  - A Pd-catalyzed addition of boronic acids to ynol ethers has been realized,
      delivering trisubstituted vinyl ethers in good yields with perfect control of the
      regio- and stereoselectivity. The reaction proceeds under mild conditions and
      exhibits excellent functional group compatibility. Moreover, the resultant
      products can be converted into pentasubstituted benzenes via the tandem Diels
      Alder/aromatization reaction. 

PMID- 23873050
TI  - Forecasting peaks of seasonal influenza epidemics.
AB  - We present a framework for near real-time forecast of influenza epidemics using a
      simulation optimization approach. The method combines an individual-based model
      and a simple root finding optimization method for parameter estimation and
      forecasting. In this study, retrospective forecasts were generated for seasonal
      influenza epidemics using web-based estimates of influenza activity from Google
      Flu Trends for 2004-2005, 2007-2008 and 2012-2013 flu seasons. In some cases, the
      peak could be forecasted 5-6 weeks ahead. This study adds to existing resources
      for influenza forecasting and the proposed method can be used in conjunction with
      other approaches in an ensemble framework. 

PMID- 23873051
TI  - Hierarchical micro/nano-structured cobalt sulfide spindles as low-cost counter
      electrodes for dye-sensitized solar cells.
AB  - Hierarchical micro/nano-structured cobalt sulfide spindles are synthesized via a
      hydrothermal method and investigated as counter electrodes for dye-sensitized
      solar cells (DSCs). It is demonstrated that DSCs with hierarchical cobalt sulfide
      spindle electrodes show an excellent photovoltaic performance competing with that
      of a device with a Pt counter electrode. 

PMID- 23873052
TI  - Clinico-biomechanical considerations on oblique corpectomy. Response to:
      Multilevel oblique corpectomy for cervical spondylotic myelopathy preserves
      segmental motion (by A.G. Chacko et al.).

PMID- 23873053
TI  - Answer to the Editorial of J. O'Dowd and A. Casey.

PMID- 23873055
TI  - Expanding the scope and influence of Acta Crystallographica Section B.

PMID- 23873054
TI  - Three dimensional analysis of brace biomechanical efficacy for patients with AIS.
AB  - PURPOSE: Corrective three dimensional (3D) effect of different braces is
      debatable. We evaluated differences in in-brace radiographic correction comparing
      a custom thoracic-lumbo-sacral-orthosis (TLSO) (T) brace to a Cheneau type TLSO
      (C) brace using 3D EOS reconstruction technology. Our primary research question
      was the 3D effect of brace on the spine and in particularly the apical vertebra
      rotation (AVR). METHODS: This was a retrospective comparative analysis of
      patients with adolescent idiopathic scoliosis who had orthogonal AP and lateral X
      rays with and without brace. A 3D image of the spine was reconstructed. Coronal,
      sagittal and axial spine parameters were measured before bracing and then on the
      first post-brace X-ray. Brace efficacy in controlling coronal, sagittal and axial
      parameters was evaluated. RESULTS: Eighteen patients treated with the C brace and
      ten patients treated with the T brace were included. No difference was found
      regarding patients' age, gender, magnitude of Cobb angle, sagittal parameters or
      AVR at inclusion. Following bracing, AVR was significantly reduced by the C brace
      compared to the T brace [average correction of 8.2 degrees  vs. 4.9 degrees  (P =
      0.02)]. Coronal and sagittal correction did not differ significantly between the
      two groups. CONCLUSIONS: By utilizing a novel 3D reconstruction technology, we
      were able to demonstrate that braces differ in their immediate effects on the
      spine. Although clinical relevance should be evaluated in a future trial we feel
      that the ability to measure treatment effects in 3D, and especially the
      transverse plane, is an important tool when evaluating different treatments.

PMID- 23873056
TI  - Why don't we find more polymorphs?
AB  - Crystal structure prediction (CSP) studies are not limited to being a search for
      the most thermodynamically stable crystal structure, but play a valuable role in
      understanding polymorphism, as shown by interdisciplinary studies where the
      crystal energy landscape has been explored experimentally and computationally.
      CSP usually produces more thermodynamically plausible crystal structures than
      known polymorphs. This article illustrates some reasons why: because (i) of
      approximations in the calculations, particularly the neglect of thermal effects
      (see S1.1); (ii) of the molecular rearrangement during nucleation and growth (see
      S1.2); (iii) the solid-state structures observed show dynamic or static disorder,
      stacking faults, other defects or are not crystalline and so represent more than
      one calculated structure (see S1.3); (iv) the structures are metastable relative
      to other molecular compositions (see S1.4); (v) the right crystallization
      experiment has not yet been performed (see S1.5) or (vi) cannot be performed (see
      S1.6) and the possibility (vii) that the polymorphs are not detected or
      structurally characterized (see S1.7). Thus, we can only aspire to a general
      predictive theory for polymorphism, as this appears to require a quantitative
      understanding of the kinetic factors involved in all possible multi-component
      crystallizations. For a specific molecule, analysis of the crystal energy
      landscape shows the potential complexity of its crystallization behaviour. 

PMID- 23873057
TI  - Modulated structure of Lu4AlCu2B9O23 from low-temperature single-crystal X-ray
      data.
AB  - A second-order phase transition with both displacive and disorder mechanisms was
      discovered in Lu4AlCu2B9O23 using single-crystal X-ray diffraction techniques by
      cooling down the sample to 110 K. Low-temperature structure modulations are
      mainly associated with Cu atoms surrounded by O atoms. The fivefold asymmetric
      environment leads to a special copper position splitting into a pair of general
      ones so that four O atoms coordinate each of them. Each copper site is 50%
      occupied at room temperature, but at lower temperature statistical disorder gives
      occupation and displacive modulations with a wavevector of q = 0.132c*.
      Tetragonal P?bar 42(1)m symmetry of the non-modulated phase transforms into an
      orthorhombic (3+1)-dimensional symmetry, P21212(00gamma)00s, whereas the ?bar 4
      axis becomes the twinning axis.

PMID- 23873058
TI  - Proton ordering in (NH4)3H(SO4)2 at low-temperature phase transitions.
AB  - Single-crystal neutron diffraction was used to investigate the H-atom disorder in
      triammonium hydrogen disulfate (TAHS), (NH4)3H(SO4)2, below room temperature.
      Crystal structure analysis of the monoclinic phase III shows an increase of
      proton ordering with decreasing temperature in the (SO4)H(SO4) dimer. Moreover,
      the NH4(+) groups on a general position begin ordering in this phase. The
      monoclinic unit cell of TAHS-IV doubles in the b direction and a slight
      distortion of SO4(2-) and NH4(+) tetrahedra is observed. The order parameter
      introduced by Landau was determined for the second-order II/III and III/IV phase
      transitions from the intensities of the superstructure reflections. TAHS-V has a
      triclinic space group and the crystal structure seems to be completely ordered
      according to a structure analysis by single-crystal X-ray diffraction
      measurements. In addition, the decisive role of the dynamical disorder of
      different ammonium groups on successive phase transitions is discussed.
      Additional peaks were observed by X-ray powder diffraction measurements at ~ 70 K
      on cooling, which refers to the V/VII phase transition. These additional peaks
      remained up to ~ 85 K on heating. They were described with a doubling of the unit
      cell along all three principal crystallographic directions. 

PMID- 23873059
TI  - Electron density distribution in tetralithium hypodiphosphate hexahydrate,
      Li4P2O6.6H2O.
AB  - Tetralithium hypodiphosphate hexahydrate, Li4P2O6.6H2O, forms a highly
      symmetrical crystal structure, where hypodiphosphate anions have ?bar 3m (D3d)
      symmetry. Analysis of the charge distribution (experimental and theoretically
      calculated) shows that the charges of the P atoms are lower than in phosphates
      and phosphonates, whereas the O charges are similar. Values of both rhoc and
      ?(2)rhoc suggest that the P-P bond is a weak covalent one, while the P-O one is
      polarized covalent, with topological parameters similar to those of P-O bonds in
      phosphates or phosphonates. Theoretical calculations show that the
      hypodiphosphate anion is relatively insensitive to its coordination environment;
      this is brought about by the vicinity of cationic P atoms. The localization and
      delocalization indices have been computed and discussed. 

PMID- 23873060
TI  - An alternative approach to rationalizing the structures of the cyclotrisilicates:
      Rb10[Si6O17], Cs8[Si6O16] and Na3Y[Si6O15] by viewing them in light of the
      extended Zintl-Klemm concept.
AB  - The structures of the three dimeric cyclotrisilicate anions [Si6O17](10-),
      [Si6O16](8-) and [Si6O15](6-) forming part of the compounds Rb10[Si6O17] or
      Rb14[Si4][Si6O17], Cs8[Si6O16] and Na3Y[Si6O15], respectively, have been
      described as different ways of condensing the more elemental cyclotrisilicate
      anions [Si3O9](6-) [Hlukhyy & Fassler (2013). Z. Anorg. Allg. Chem. 639, 231
      233]. Such a description prevents a rational explanation of the connectivity
      between the Si atoms. So, in this article the Si skeletons of the above silicate
      anions are put on a common basis in light of the extended Zintl-Klemm concept.
      Their connectivity is directly related to the ratio Psi-S/Psi-P resulting from
      the number of electrons transferred from the electropositive Na, Y, Rb and Cs
      atoms, offering a new example of the fact that there exists a univocal link
      between chemical composition (in terms of pseudo-atoms) and structure: the
      generalized Zintl-Klemm concept. The three skeletons fit the connectivity of
      hypothetical Zintl polyanions of composition [Psi-S4P2](10-), [Psi-S2P4](8-) and
      [Psi-P6](6-) respectively. 

PMID- 23873061
TI  - Structure and properties of domperidone and its succinate salt.
AB  - This paper describes the structure and properties of the drug domperidone and a
      novel 1:1 domperidone succinate salt. The new salt is characterized by means of
      thermal, spectroscopic, microscopic and powder diffraction measurements. The
      crystal structures of the salt and, for the first time, of pure domperidone have
      been determined by means of single-crystal X-ray diffraction. In both structures,
      the piperidine ring of domperidone adopts the expected chair conformation, and
      supramolecular centrosymmetric R2(2)(8) motifs are formed by N-H...O hydrogen
      bonds between chlorine-substituted oxobenzimidazolyl groups. Further N-H...O
      hydrogen bonds occur between non-substituted oxobenzimidazolyl groups and the
      resulting C(4) motifs originates hydrogen-bonded chains, extending along the
      crystallographic b axis. In the salt, a single N-H...O hydrogen bond forms
      between the protonated nitrogen of the piperidine ring and the carboxylic O atom
      of the succinate ion. Two alternative and mutually exclusive positions for the
      nonsubstituted oxobenzimidazolyl group have also been observed; this disorder
      makes the hydrogen-bonded chains originating from the bicyclic group polar. The
      dissolution behaviour of the salt in dosage form is compared with two reference
      commercial products. The salt shows an increased solubility, a characteristic
      that could be of great advantage from a pharmaceutical view point. 

PMID- 23873062
TI  - The importance of screening solid-state phases of a racemic modification of a
      chiral drug: thermodynamic and structural characterization of solid-state phases
      of etiracetam.
AB  - In this contribution different solid-state forms of the racemic compound (RS)-2
      (2-oxo-pyrrolidin-1yl)-butyramide are studied from a structural and thermal point
      of view. Three different solid-state phases were identified, including two
      polymorphs and one hydrate phase. Comparison is made with the structure of the
      (S)-enantiomer, for which only one solid-state phase is known. The basic
      structural motif found in both polymorphs of the racemic compound is similar, but
      the basic motif observed for the hydrate differs. These synthons could in
      principle be used in future polymorph prediction studies to screen for possible
      alternative forms of the enantiopure compound. Based on the structure of the
      hydrate, further efforts should therefore be made in order to identify a hydrate
      structure of the enantiopure compound. Studying the different phases of a racemic
      compound can therefore help to guide polymorphic screening of an enantiopure
      compound. 

PMID- 23873063
TI  - Role of chloroform and dichloromethane solvent molecules in crystal packing: an
      interaction propensity study.
AB  - Using the Cambridge Structural Database (CSD), it is shown that the acidic C-H
      donors of chloroform and dichloromethane, respectively, form hydrogen bonds with
      N, O, S, halides or carbon-bound halogens in 82% and 77% of structures in which
      such interactions can occur. This hydrogen-bond potency is retained to a
      significant degree even in the presence of the more conventional O-H and N-H
      donors. The hydrogen-bond propensities exhibited by the C-H protons in CHCl3 and
      CH2Cl2 are similar to those of the acetylenic C-C=C-H proton. However,
      involvement of the Cl atoms of CHCl3 and CH2Cl2 in non-bonded interactions is
      rather limited: the propensities for formation of (O or N)-H...Cl bonds are only
      6% in both cases, while the propensities for the formation of halogen-halogen
      bonds is generally < 15%, with only Cl...Br interactions having slightly higher
      values. While C(phenyl)-H...Cl interactions are commonly observed, they are of
      low propensity and have distances at the upper end of the van der Waals limit. We
      conclude that the acidic C-H protons in chloroform and dichloromethane solvent
      molecules play a clear role in the involvement of these molecules in molecular
      aggregation in crystal structures, and this is exemplified by hydrogen-bond
      predictions made using the statistical propensity tool which is now part of the
      CSD system.

PMID- 23873064
TI  - Influence of supramolecular structures in crystals on parallel stacking
      interactions between pyridine molecules.
AB  - Parallel stacking interactions between pyridines in crystal structures and the
      influence of hydrogen bonding and supramolecular structures in crystals on the
      geometries of interactions were studied by analyzing data from the Cambridge
      Structural Database (CSD). In the CSD 66 contacts of pyridines have a parallel
      orientation of molecules and most of these pyridines simultaneously form hydrogen
      bonds (44 contacts). The geometries of stacked pyridines observed in crystal
      structures were compared with the geometries obtained by calculations and
      explained by supramolecular structures in crystals. The results show that the
      mean perpendicular distance (R) between pyridine rings with (3.48 A) and without
      hydrogen bonds (3.62 A) is larger than that calculated, because of the influence
      of supramolecular structures in crystals. The pyridines with hydrogen bonds show
      a pronounced preference for offsets of 1.25-1.75 A, close to the position of the
      calculated minimum (1.80 A). However, stacking interactions of pyridines without
      hydrogen bonds do not adopt values at or close to that of the calculated offset.
      This is because stacking interactions of pyridines without hydrogen bonds are
      less strong, and they are more susceptible to the influence of supramolecular
      structures in crystals. These results show that hydrogen bonding and
      supramolecular structures have an important influence on the geometries of
      stacked pyridines in crystals. 

PMID- 23873065
TI  - Decafluorocyclohex-1-ene at 4.2 K - crystal structure and theoretical analysis of
      weak interactions.
AB  - The crystal structure of 1,2,3,3,4,4,5,5,6,6-decafluorocyclohex-1-ene
      (decafluorocyclohex-1-ene, C6F10) was solved in direct space from neutron powder
      diffraction data previously collected at 4.2 K [Pawley, G. S. (1981). J. Appl.
      Cryst. 14, 357-361] and refined by energy minimization in the solid state. To
      optimize the positions of the 64 atoms in the monoclinic computational cell the
      PBESOL and hybrid PBE0 functionals were used. The crystal structure of the title
      compound, which is liquid at room temperature, is built of antiparallel pairs of
      molecules assembled into molecular columns stacked along the a axis. Dominating
      the crystal-building forces are weak intermolecular dispersion interactions.
      Bonding conditions in the structure were analysed by theoretical molecular
      calculations of representative next-neighbor molecular dimers carried out using
      dispersion-corrected density functional theory (DFT) functionals and the SCS-MP2
      wavefunction method. The largest interaction energy is of the order of ~ 21 kJ
      mol(-1), above the interaction energy of a benzene dimer (11.3 kJ mol(-1)) and
      close to that of a water dimer (20.9 kJ mol(-1)). The interaction energy for the
      second most stable dimer can be compared with either that of a benzene dimer or
      of a C-H...pi hydrogen bond. The remaining five weakly interacting dimers (~ 4.2
      8.4 kJ mol(-1)) can be characterized as having stronger interactions than those
      of methane dimers (-2.2 kJ mol(-1)), but weaker than those of benzene molecule
      pairs or weak C-H...C interactions for instance. 

PMID- 23873066
TI  - Methylthioureas and their morpholine and dioxane adducts; hydrogen-bonding
      patterns.
AB  - We have redetermined the known structures of (i) methylthiourea (MTU) and (ii)
      1,1-dimethylthiourea (1,1-DMTU), and investigated the structure of 1,3
      dimethylthiourea (1,3-DMTU), which was however severely disordered. We report the
      structures of crystalline adducts of (iii) MTU with morpholine (1:1), (iv) 1,1
      DMTU with 1,4-dioxane (2:1) and (v) 1,3-DMTU with 1,4-dioxane (2:1). Finally,
      (vi) we determined the structure of tetramethylthiourea (TetMTU). (i) In both
      independent molecules of MTU, the methyl group is trans to the C=S group across
      the C-N bond. The two molecules are connected to form an R2(2)(8) dimer by mutual
      N-H...S=C interactions. The packing involves six N-H...S=C interactions and is
      three-dimensional. (ii) The packing of the MTU-morpholine adduct is a layer
      structure, within which both molecules form linear aggregates parallel to the b
      axis. (iii) The packing of 1,1-DMTU involves N-H...S=C hydrogen bonds forming a
      corrugated layer structure. (iv) In the 2:1 adduct between 1,1-DMTU and 1,4
      dioxane, the DMTU molecule occupies a general position whereas the dioxane
      molecule lies across an inversion centre. The crystal packing involves chains of
      alternating 1,1-DMTU R2(2)(8) dimers and dioxanes, both across inversion centres.
      (v) In the 2:1 adduct between 1,3-DMTU and dioxane, the 1,3-DMTU molecule
      occupies a general position, while the dioxane molecule lies across an inversion
      centre. One methyl group of the DMTU is trans and one cis to the sulfur across
      the corresponding C-N bond. The molecules form chains of alternating 1,3-DMTU
      R2(2)(8) dimers and dioxanes, both across inversion centres. Crystals of the 2:1
      adduct between 1,3-DMTU and morpholine were also obtained, and were isotypic with
      the dioxane adduct. The morpholine molecule is disordered across the inversion
      centre. (vi) The molecule of TetMTU displays crystallographic twofold symmetry.
      Significant distortions reflect the steric pressure between methyl groups trans
      to sulfur. The packing of TetMTU involves only a weak hydrogen bond, C
      Hmethyl...S, which connects the molecules to form layers. 

PMID- 23873067
TI  - Zn- and Co-based layered double hydroxides: prediction of the a parameter from
      the fraction of trivalent cations and vice versa.
AB  - A recently proposed method to calculate the a parameter of the unit cell of
      layered double hydroxides from the fraction of trivalent cations is extended to
      Zn- and Co-based phases. It is shown to be useful as a sanity test for extant and
      future structure determinations and computer-simulation studies. 

PMID- 23873069
TI  - Adjusting for selection bias in longitudinal analyses using simultaneous
      equations modeling: the relationship between employment transitions and mental
      health.
AB  - BACKGROUND: Effects of labor force participation on mental health can be
      difficult to discern due to the possibility of selection bias. Previous research
      typically adjusts for direct selection (reverse causality) but ignores indirect
      selection (unmeasured confounders). METHODS: We investigate the relationship
      between men's employment transitions and mental health using a dynamic
      simultaneous equations model applied to data from the British Household Panel
      Survey (1991-2009). Outcome is self-reported distress and anxiety as summed on a
      12-point scale. We allow for direct selection by allowing prior mental health to
      affect both subsequent mental health and employment transitions in the joint
      model. We adjust for indirect selection by allowing for residual correlation
      between mental health and employment. RESULTS: Moving from unemployment to
      employment was strongly associated with an improvement in mental health, whereas
      becoming unemployed was detrimental. However, these associations were attenuated
      by unmeasured confounders. After adjustment for indirect selection, the increased
      distress and anxiety associated with becoming unemployed decreased from 2.5 (95%
      confidence interval = 2.2 to 2.7) to 2.2 (2.0 to 2.5). (A change of 2.5 equates
      to half a standard deviation on the 12-point scale.) The improvement with moving
      from unemployment to employment was also weakened slightly (from -2.1 [-2.4 to 
      1.7] to -1.8 [-2.1 to -1.5]). CONCLUSIONS: There was strong evidence of indirect
      selection, but less support for direct selection. Nevertheless, the effects on
      psychological health of transitions between employment and unemployment, and
      between employment and economic inactivity, remained substantial after adjusting
      for selection.

PMID- 23873070
TI  - Risk of acute myocardial infarction: dyslipidemia more detrimental for men than
      women.
AB  - BACKGROUND: Endogenous estrogens prevent lipid peroxidation, which is pivotal in
      atherogenesis. Dyslipidemia may therefore be more dangerous for men than for
      women as a risk factor for acute myocardial infarction (AMI). A differential
      effect by sex has not been empirically established. METHODS: In a prospective
      population-based cohort study of 23,525 women and 20,725 men younger than 60
      years of age at baseline, we followed participants for 12 years for a first AMI.
      By calculating the proportion of AMI among men with dyslipidemia attributable to
      the synergism between male sex and dyslipidemia, we assessed the degree to which
      dyslipidemia is more detrimental for men than for women. RESULTS: Dyslipidemia
      and male sex enhanced the effect of one another in relation to AMI risk. The
      proportion of AMI cases among men with dyslipidemia attributable to this
      synergism alone was 0.46 (95% confidence interval = 0.35 to 0.57) for high total
      serum cholesterol, 0.23 (0.05 to 0.41) for low high-density lipoprotein (HDL)
      cholesterol, and 0.52 (0.42 to 0.62) for high non-HDL cholesterol. In contrast,
      obesity and hypertension were equally detrimental for men and women in relation
      to AMI risk, with a corresponding attributable proportion of 0.02 (-0.21 to 0.25)
      and -0.01 (-0.27 to 0.24), respectively. CONCLUSIONS: Current clinical guidelines
      of dyslipidemia management do not distinguish between men and women in relation
      to primary prevention of AMI. Our results suggest that in middle age,
      dyslipidemia is much more detrimental for men than for women, and that preventing
      dyslipidemia has a greater potential to reduce the occurrence of AMI among men.

PMID- 23873071
TI  - Autism spectrum disorder phenotypes and prenatal exposure to methylmercury.
AB  - BACKGROUND: There continues to be public concern that mercury exposure and autism
      spectrum disorder (ASD) may be associated. The primary source of exposure to
      organic mercury in humans is to methylmercury from fish consumption. We evaluated
      the association between prenatal methylmercury exposure and ASD phenotype in
      children and adolescents in the Republic of Seychelles, where fish consumption is
      high. METHODS: We administered the Social Communication Questionnaire to parents
      of a cohort of 1784 children, adolescents, and young adults. The Social
      Responsiveness Scale was administered to teachers of 537 cohort subjects at about
      10 years of age. Prenatal exposure to methylmercury was measured in maternal hair
      samples collected at or near the time of birth. Multivariable regression models
      evaluated the relationship between prenatal methylmercury exposure and ASD
      phenotypic scores, adjusting for relevant covariates. RESULTS: The mean prenatal
      methylmercury exposure for subjects in the analysis was 8.4 ppm (standard
      deviation [SD] = 5.7). The mean Social Communication Questionnaire score was 8.0
      (SD = 4.4). The mean prenatal methylmercury exposure for subjects with Social
      Responsiveness Scale scores was 6.7 ppm (SD = 4.4) and the mean Social
      Responsiveness Scale score was 57.6 (SD = 26.8). No consistent association
      between prenatal methylmercury exposure and ASD screening instrument was found,
      using linear and nonlinear regression analyses. CONCLUSIONS: Prenatal exposure to
      methylmercury was not associated with ASD phenotypic behaviors in our cohort of
      high fish consumers. Our findings contribute to the growing literature suggesting
      that exposure to methylmercury does not play an important role in the development
      of ASD phenotypic behavior.

PMID- 23873072
TI  - Antidepressant use and risk for preeclampsia.
AB  - BACKGROUND: Prior studies suggest that women who use antidepressants during
      pregnancy have an increased risk for preeclampsia, yet the comparative safety of
      specific antidepressants remains unclear. US nationwide Medicaid Analytic eXtract
      (MAX) data have not been used to study medication safety during pregnancy.
      METHODS: We identified 100,942 pregnant women with depression from 2000 to 2007
      MAX data. We used pharmacy dispensing records to ascertain exposure to selective
      serotonin reuptake inhibitor (SSRI), serotonin-norepenephrine reuptake inhibitor
      (SNRI), tricyclic, bupropion, other antidepressant monotherapy or polytherapy,
      and specific antidepressants, during the second trimester and first half of the
      third trimester. Relative risks (RRs) and 95% confidence intervals (CIs) were
      adjusted for delivery year, preeclampsia risk factors, depression severity
      proxies, other antidepressant indications, other medications, and healthcare
      utilization. RESULTS: The risk of preeclampsia was 5.4% among women with
      depression and no antidepressant exposure. Compared with these women, the risk
      for preeclampsia was higher among those receiving SNRI (RR: 1.52, 95% CI = 1.26
      1.83) and tricyclic monotherapy (RR: 1.62, 95% CI = 1.23-2.12), but not SSRI
      monotherapy (RR: 1.00, 95% CI = 0.93-1.07) or other antidepressants. Compared
      with women receiving SSRI monotherapy, preeclampsia risk was higher among women
      with SNRI (RR: 1.54, 95% CI = 1.28-1.86) and tricyclic (RR: 1.64, 95% CI = 1.25
      2.16) monotherapy. None of the specific SSRIs was associated with preeclampsia.
      The RR with venlafaxine was 1.57 (95% CI = 1.29-1.91) and with amitriptyline 1.72
      (95% CI = 1.24-2.40). CONCLUSIONS: In this population, SNRIs and tricyclics were
      associated with a higher risk of preeclampsia than SSRIs.

PMID- 23873073
TI  - Respiratory effects of a reduction in outdoor air pollution concentrations.
AB  - BACKGROUND: Air pollution has been associated with respiratory health effects.
      There is little direct evidence that reductions in air pollution related to
      abatement policies lead to actual improvement in respiratory health. We assessed
      whether a reduction in (traffic policy-related) air pollution concentrations was
      associated with changes in respiratory health. METHODS: Air pollution
      concentrations and respiratory health were measured in 2008 and 2010 at eight
      busy urban streets and at four suburban background control locations. Respiratory
      function was assessed twice in 661 residents by spirometry and measurements of
      airway resistance. Nitric oxide (NO) in exhaled air was measured as a marker for
      airway inflammation. RESULTS: Air pollution concentrations were lower in 2010
      than in 2008. The declines in pollutants varied among locations, with the largest
      decline observed in a street with a large reduction in traffic intensity. In
      regression analyses adjusted for important covariates, reductions in
      concentrations of soot, NO2, NOx, Cu, and Fe were associated with increases in
      forced vital capacity (FVC) (~1% increase per interquartile range [IQR] decline).
      Airway resistance decreased with a decline in particulate matter (PM10) and PM2.5
      (9% per IQR), although these associations were somewhat less consistent. No
      associations were found with exhaled NO. Results were driven largely by one
      street where traffic-related air pollution showed the largest reduction. Forced
      expiratory volume and FVC improved by 3% to 6% in residents of this street
      compared with suburban background residents. This was accompanied by a suggestive
      reduction in airway resistance. CONCLUSIONS: Reductions in air pollution may lead
      to small improvements in respiratory function.

PMID- 23873074
TI  - High arsenic in rice is associated with elevated genotoxic effects in humans.
AB  - Arsenic in drinking water may cause major deleterious health impacts including
      death. Although arsenic in rice has recently been demonstrated to be a potential
      exposure route for humans, there has been to date no direct evidence for the
      impact of such exposure on human health. Here we show for the first time, through
      a cohort study in West Bengal, India, involving over 400 human subjects not
      otherwise significantly exposed to arsenic through drinking water, elevated
      genotoxic effects, as measured by micronuclei (MN) in urothelial cells,
      associated with the staple consumption of cooked rice with >200 MUg/kg arsenic.
      Further work is required to determine the applicability to populations with
      different dietary and genetic characteristics, but with over 3 billion people in
      the world consuming rice as a staple food and several percent of this rice
      containing such elevated arsenic concentrations, this study raises considerable
      concerns over the threat to human health.

PMID- 23873075
TI  - Visible light driven type II heterostructures and their enhanced photocatalysis
      properties: a review.
AB  - Considerable efforts have been devoted to enhancing the photocatalytic activity
      and solar energy utilization of photocatalysts. The fabrication of type II
      heterostructures plays an important role in photocatalysts modification and has
      been extensively studied. In this review, we briefly trace the application of
      type II heterostructured semiconductors in the area of environmental remediation
      and water splitting, summarize major fabrication methods, describe some of the
      progress and resulting achievements, and discuss the future prospects. The scope
      of this review covers a variety of type II heterostructures, focusing
      particularly on TiO2 and ZnO based visible light driven type II 0D and 1D
      heterostructured photocatalysts. Some other low dimensional nanomaterials which
      have shown high-performance photocatalysis are also presented. We expect this
      review to provide a guideline for readers to gain a clear picture of fabrication
      and application of type II heterostructures. 

PMID- 23873076
TI  - Molecular cloning, characterization, and expression pattern of the ultraspiracle
      gene homolog (RXR/USP) from the hemimetabolous insect Periplaneta americana
      (Dictyoptera, Blattidae) during vitellogenesis.
AB  - Ecdysteroid and sequiterpenoids juvenile hormones play a gonadotrophic role in
      the insect adult female vitellogenesis. The molecular basis of hormone action has
      been analyzed in great detail in flies and moths, but rarely in primitive insect
      orders. The primitive hemimetabolous insect Periplaneta americana was used, as a
      model, to isolate and characterize, for the first time, two cDNAs of RXR/USP, a
      component of the heterodimeric ecdysone receptor. These two cDNAs correspond to
      two isoforms, named PamRXR-S (short form) and PamRXR-L (long form). Both are
      identical except for 25 amino acids deletion/insertion located in the loop
      between helices H1 and H3 of the ligand-binding domain. The two isoforms are
      differentially expressed in different tissues as revealed by RT-PCR and northern
      blot analysis. In fat body, brain, ovary, and muscle tissues, the predominant
      form was PamRXR-S, whereas PamRXR-L was abundant in ovaries. The PamRXR
      transcript was detected during all stages of vitellogenesis in the fat body with
      different levels. It was little low during the early vitellogenic period (days 2,
      3), then a peak of increase was detected during days 4-6 (day 5) which was
      followed by another peak of increase at the end of vitellogenesis, day 9. We
      assumed that PamRXR might play a dual role of induction of vitellogenin through
      JH at early vitellogenesis and suppression through 20E during late
      vitellogenesis. The present work will pave the way for several other
      investigations to understand both the ecdysteroid-dependent genetic hierarchy and
      JH mechanism controlling vitellogenesis in the American cockroach, P. americana. 

PMID- 23873077
TI  - Crystal structure of shrimp arginine kinase in binary complex with arginine-a
      molecular view of the phosphagen precursor binding to the enzyme.
AB  - Arginine kinase (AK) is a key enzyme for energetic balance in invertebrates.
      Although AK is a well-studied system that provides fast energy to invertebrates
      using the phosphagen phospho-arginine, the structural details on the AK-arginine
      binary complex interaction remain unclear. Herein, we determined two crystal
      structures of the Pacific whiteleg shrimp (Litopenaeus vannamei) arginine kinase,
      one in binary complex with arginine (LvAK-Arg) and a ternary transition state
      analog complex (TSAC). We found that the arginine guanidinium group makes ionic
      contacts with Glu225, Cys271 and a network of ordered water molecules. On the
      zwitterionic side of the amino acid, the backbone amide nitrogens of Gly64 and
      Val65 coordinate the arginine carboxylate. Glu314, one of proposed acid-base
      catalytic residues, did not interact with arginine in the binary complex. This
      residue is located in the flexible loop 310-320 that covers the active site and
      only stabilizes in the LvAK-TSAC. This is the first binary complex crystal
      structure of a guanidine kinase in complex with the guanidine substrate and could
      give insights into the nature of the early steps of phosphagen biosynthesis. 

PMID- 23873079
TI  - Asymmetric anti-aldol addition of achiral ketones via chiral N-amino cyclic
      carbamate hydrazones.
AB  - The asymmetric anti-aldol addition of ketone-derived donors and aldehyde
      acceptors is described. Asymmetric induction is achieved through the use of
      chiral N-amino cyclic carbamate (ACC) auxiliaries. The transformation exhibits
      essentially perfect anti-diastereoselectivity and enantioselectivity, and has the
      unusual feature of proceeding via thermodynamic, rather than kinetic control. 

PMID- 23873078
TI  - Romance of the three domains: how cladistics transformed the classification of
      cellular organisms.
AB  - Cladistics is a biological philosophy that uses genealogical relationship among
      species and an inferred sequence of divergence as the basis of classification.
      This review critically surveys the chronological development of biological
      classification from Aristotle through our postgenomic era with a central focus on
      cladistics. In 1957, Julian Huxley coined cladogenesis to denote splitting from
      subspeciation. In 1960, the English translation of Willi Hennig's 1950 work,
      Systematic Phylogenetics, was published, which received strong opposition from
      pheneticists, such as numerical taxonomists Peter Sneath and Robert Sokal, and
      evolutionary taxonomist, Ernst Mayr, and sparked acrimonious debates in 1960
      1980. In 1977-1990, Carl Woese pioneered in using small subunit rRNA gene
      sequences to delimitate the three domains of cellular life and established major
      prokaryotic phyla. Cladistics has since dominated taxonomy. Despite being
      compatible with modern microbiological observations, i.e. organisms with unusual
      phenotypes, restricted expression of characteristics and occasionally being
      uncultivable, increasing recognition of pervasiveness and abundance of horizontal
      gene transfer has challenged relevance and validity of cladistics. The mosaic
      nature of eukaryotic and prokaryotic genomes was also gradually discovered. In
      the mid-2000s, high-throughput and whole-genome sequencing became routine and
      complex geneologies of organisms have led to the proposal of a reticulated web of
      life. While genomics only indirectly leads to understanding of functional
      adaptations to ecological niches, computational modeling of entire organisms is
      underway and the gap between genomics and phenetics may soon be bridged.
      Controversies are not expected to settle as taxonomic classifications shall
      remain subjective to serve the human scientist, not the classified. 

PMID- 23873080
TI  - Seeing ourselves as moral agents in relation to our organizational and
      sociopolitical contexts : commentary on "a reflection on moral distress in
      nursing together with a current application of the concept" by Andrew Jameton.

PMID- 23873081
TI  - DNA targeting specificity of RNA-guided Cas9 nucleases.
AB  - The Streptococcus pyogenes Cas9 (SpCas9) nuclease can be efficiently targeted to
      genomic loci by means of single-guide RNAs (sgRNAs) to enable genome editing.
      Here, we characterize SpCas9 targeting specificity in human cells to inform the
      selection of target sites and avoid off-target effects. Our study evaluates >700
      guide RNA variants and SpCas9-induced indel mutation levels at >100 predicted
      genomic off-target loci in 293T and 293FT cells. We find that SpCas9 tolerates
      mismatches between guide RNA and target DNA at different positions in a sequence
      dependent manner, sensitive to the number, position and distribution of
      mismatches. We also show that SpCas9-mediated cleavage is unaffected by DNA
      methylation and that the dosage of SpCas9 and sgRNA can be titrated to minimize
      off-target modification. To facilitate mammalian genome engineering applications,
      we provide a web-based software tool to guide the selection and validation of
      target sequences as well as off-target analyses. 

PMID- 23873082
TI  - Genomic landscapes of Chinese hamster ovary cell lines as revealed by the
      Cricetulus griseus draft genome.
AB  - Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred
      production host for many therapeutic proteins. Although genetic heterogeneity
      among CHO cell lines has been well documented, a systematic, nucleotide
      resolution characterization of their genotypic differences has been stymied by
      the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb
      draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring
      24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines
      from the CHO-K1, DG44 and CHO-S lineages. This analysis identified hamster genes
      missing in different CHO cell lines, and detected >3.7 million single-nucleotide
      polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many
      mutations are located in genes with functions relevant to bioprocessing, such as
      apoptosis. The details of this genetic diversity highlight the value of the
      hamster genome as the reference upon which CHO cells can be studied and
      engineered for protein production. 

PMID- 23873083
TI  - Single-cell gene expression analysis reveals genetic associations masked in whole
      tissue experiments.
AB  - Gene expression in multiple individual cells from a tissue or culture sample
      varies according to cell-cycle, genetic, epigenetic and stochastic differences
      between the cells. However, single-cell differences have been largely neglected
      in the analysis of the functional consequences of genetic variation. Here we
      measure the expression of 92 genes affected by Wnt signaling in 1,440 single
      cells from 15 individuals to associate single-nucleotide polymorphisms (SNPs)
      with gene-expression phenotypes, while accounting for stochastic and cell-cycle
      differences between cells. We provide evidence that many heritable variations in
      gene function--such as burst size, burst frequency, cell cycle-specific
      expression and expression correlation/noise between cells--are masked when
      expression is averaged over many cells. Our results demonstrate how single-cell
      analyses provide insights into the mechanistic and network effects of genetic
      variability, with improved statistical power to model these effects on gene
      expression.

PMID- 23873084
TI  - Overexpression of microRNA OsmiR397 improves rice yield by increasing grain size
      and promoting panicle branching.
AB  - Increasing grain yields is a major focus of crop breeders around the world. Here
      we report that overexpression of the rice microRNA (miRNA) OsmiR397, which is
      naturally highly expressed in young panicles and grains, enlarges grain size and
      promotes panicle branching, leading to an increase in overall grain yield of up
      to 25% in a field trial. To our knowledge, no previous report has shown a
      positive regulatory role of miRNA in the control of plant seed size and grain
      yield. We determined that OsmiR397 increases grain yield by downregulating its
      target, OsLAC, whose product is a laccase-like protein that we found to be
      involved in the sensitivity of plants to brassinosteroids. As miR397 is highly
      conserved across different species, our results suggest that manipulating miR397
      may be useful for increasing grain yield not only in rice but also in other
      cereal crops. 

PMID- 23873085
TI  - Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia
      lipolytica.
AB  - The availability of the omega-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) is currently limited because they are produced mainly
      by marine fisheries that cannot keep pace with the demands of the growing market
      for these products. A sustainable non-animal source of EPA and DHA is needed.
      Metabolic engineering of the oleaginous yeast Yarrowia lipolytica resulted in a
      strain that produced EPA at 15% of dry cell weight. The engineered yeast lipid
      comprises EPA at 56.6% and saturated fatty acids at less than 5% by weight, which
      are the highest and the lowest percentages, respectively, among known EPA
      sources. Inactivation of the peroxisome biogenesis gene PEX10 was crucial in
      obtaining high EPA yields and may increase the yields of other commercially
      desirable lipid-related products. This technology platform enables the production
      of lipids with tailored fatty acid compositions and provides a sustainable source
      of EPA. 

PMID- 23873087
TI  - Palladium-catalyzed regio- and chemoselective ortho-benzylation of C-H bond using
      a functionalizable primary amide directing group: a concise synthesis of
      dibenzo[b,e]azepin-6-ones.
AB  - A palladium-catalyzed regio- and chemoselective direct benzylation of primary
      benzamides with 2-bromobenzyl bromides under a mild basic condition has been
      developed affording various substituted diarylmethanes in good yields.
      Furthermore, the directing amide group (-CONH2) was subjected to intramolecular N
      arylation with the aryl bromide moiety present in diarylmethanes leading to a
      concise synthesis of dibenzoazepinones. 

PMID- 23873086
TI  - Photoreceptor precursors derived from three-dimensional embryonic stem cell
      cultures integrate and mature within adult degenerate retina.
AB  - Irreversible blindness caused by loss of photoreceptors may be amenable to cell
      therapy. We previously demonstrated retinal repair and restoration of vision
      through transplantation of photoreceptor precursors obtained from postnatal
      retinas into visually impaired adult mice. Considerable progress has been made in
      differentiating embryonic stem cells (ESCs) in vitro toward photoreceptor
      lineages. However, the capability of ESC-derived photoreceptors to integrate
      after transplantation has not been demonstrated unequivocally. Here, to isolate
      photoreceptor precursors fit for transplantation, we adapted a recently reported
      three-dimensional (3D) differentiation protocol that generates neuroretina from
      mouse ESCs. We show that rod precursors derived by this protocol and selected via
      a GFP reporter under the control of a Rhodopsin promoter integrate within
      degenerate retinas of adult mice and mature into outer segment-bearing
      photoreceptors. Notably, ESC-derived precursors at a developmental stage similar
      to postnatal days 4-8 integrate more efficiently compared with cells at other
      stages. This study shows conclusively that ESCs can provide a source of
      photoreceptors for retinal cell transplantation. 

PMID- 23873088
TI  - A translational pharmacology approach to understanding the predictive value of
      abuse potential assessments.
AB  - Within the drug development industry the assessment of abuse potential for novel
      molecules involves the generation and review of data from multiple sources,
      ranging from in-vitro binding and functional assays through to in-vivo
      nonclinical models in mammals, as well as collection of information from studies
      in humans. This breadth of data aligns with current expectations from regulatory
      agencies in both the USA and Europe. To date, there have been a limited number of
      reviews on the predictive value of individual models within this sequence, but
      there has been no systematic review on how each of these models contributes to
      our overall understanding of abuse potential risk. To address this, we analyzed
      data from 100 small molecules to compare the predictive validity for drug
      scheduling status of a number of models that typically contribute to the abuse
      potential assessment package. These models range from the assessment of in-vitro
      binding and functional profiles at receptors or transporters typically associated
      with abuse through in-vivo models including locomotor activity, drug
      discrimination, and self-administration in rodents. Data from subjective report
      assessments in humans following acute dosing of compounds were also included. The
      predictive value of each model was then evaluated relative to the scheduling
      status of each drug in the USA. In recognition of the fact that drug scheduling
      can be influenced by factors other than the pharmacology of the drug, we also
      evaluated the predictive value of each assay for the outcome of the human
      subjective effects assessment. This approach provides an objective and
      statistical assessment of the predictive value of many of the models typically
      applied within the pharmaceutical industry to evaluate abuse potential risk. In
      addition, the impact of combining information from multiple models was examined.
      This analysis adds to our understanding of the predictive value of each model,
      allows us to critically evaluate the benefits and limitations of each model, and
      provides a method for identifying opportunities for improving our assessment and
      prediction of abuse liability risk in the future. 

PMID- 23873089
TI  - Synergy between chemotherapeutic agents and CTLA-4 blockade in preclinical tumor
      models.
AB  - Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) binding agent, has proven
      to be an effective monotherapy for metastatic melanoma and has shown antitumor
      activity in trials when administered with other therapeutic agents. We
      hypothesized that the combination of ipilimumab with chemotherapeutic agents,
      such as ixabepilone, paclitaxel, etoposide, and gemcitabine, may produce
      therapeutic synergy based on distinct but complementary mechanisms of action for
      each drug and unique cellular targets. This concept was investigated using a
      mouse homolog of ipilimumab in preclinical murine tumor models, including SA1N
      fibrosarcoma, EMT-6 mammary carcinoma, M109 lung carcinoma, and CT-26 colon
      carcinoma. Results of CTLA-4 blockade in combination with one of various
      chemotherapeutic agents demonstrate that synergy occurs in settings where either
      agent alone was not effective in inducing tumor regression. Furthermore, when
      combined with CTLA-4 blockade, ixabepilone, etoposide, and gemcitabine elicited
      prolonged antitumor effects in some murine models with induction of a memory
      immune response. Future investigations are warranted to determine which specific
      chemo-immunotherapy combinations, if any, will produce synergistic antitumor
      effects in the clinical setting.

PMID- 23873092
TI  - ClC-3 deficiency prevents apoptosis induced by angiotensin II in endothelial
      progenitor cells via inhibition of NADPH oxidase.
AB  - Endothelial progenitor cells (EPCs) play an important role in postnatal
      neovascularization and re-endothelialization in response to tissue ischemia and
      endothelial injury. It is reported that the circulating EPCs number is decreased
      during hypertension. However, the detailed mechanism is still unclear. Our
      previous studies have shown that ClC-3 chloride channel is up-regulated with the
      development of hypertension. This study aims to test whether ClC-3 participates
      in EPC apoptosis under the condition of increased oxidative stress in angiotensin
      II (Ang II)-induced hypertension. The results showed that stimulation with 10(
      6)mol/L Ang II significantly up-regulated the endogenous ClC-3 expression and
      increased intracellular reactive oxygen species (ROS) generation in EPCs of wild
      type mice, accompanied by an enhanced NADPH oxidase activity and the expression
      of gp91(phox) (NOX-2), a key catalytic subunit of NADPH oxidase. However, these
      effects of Ang II were significantly reduced in EPCs of ClC-3(-/-) mice. Compared
      with control, treatment with Ang II induced EPCs apoptosis in wild type mice,
      concomitantly with declined Bcl-2/Bax ratio, depressed mitochondrial membrane
      potential and activation of poly(ADP-ribose) polymerase, which was remarkably
      prevented by both ClC-3 knockout and NADPH oxidase inhibitor apocynin. In
      addition, the role of ClC-3 deficiency in protecting EPCs against Ang II-induced
      oxidative stress and apoptosis was further confirmed in Ang II-infused
      hypertensive mice in vivo. In conclusion, ClC-3 deficiency inhibited Ang II
      induced EPC apoptosis via suppressing ROS generation derived from NADPH oxidase. 

PMID- 23873093
TI  - Electrochemical biosensors using aptamers for theranostics.
AB  - Theranostics, a new term consisting of the words "therapy" and "diagnostics,"
      represents the concept of selecting specific patients for appropriate drug
      administration using diagnostics. For the development of a molecular targeting
      drug, the theranostics approach is effective. Therefore, the market for molecular
      diagnostics is likely to grow at an extraordinary rate over the next 10 years. In
      this review, we focus on aptamer-based electrochemical biosensors for
      theranostics. Aptamers are molecular recognition elements that can bind to
      various target molecules from small compounds to proteins with affinities and
      specificities comparable to those of antibodies. Inasmuch as various molecules
      would be targeted for analysis using theranostics, aptamer-based biosensors would
      be an attractive format because they can be developed for various molecules using
      the same sensing format. Although a diverse sensing system can be constructed, we
      focus on electrochemical biosensors in this review because they can measure
      biomarkers rapidly in a miniaturized sensing system with low cost, such as blood
      glucose sensors. We summarize the sensing systems of aptamer-based
      electrochemical biosensors and discuss their advantages for theranostics.

PMID- 23873091
TI  - Pretreatment anterior cingulate activity predicts antidepressant treatment
      response in major depressive episodes.
AB  - Major depressive disorder leads to substantial individual and socioeconomic
      costs. Despite the ongoing efforts to improve the treatment for this condition, a
      trial-and-error approach until an individually effective treatment is established
      still dominates clinical practice. Searching for clinically useful treatment
      response predictors is one of the most promising strategies to change this
      quandary therapeutic situation. This study evaluated the predictive value of a
      biological and a clinical predictor, as well as a combination of both.
      Pretreatment EEGs of 31 patients with a major depressive episode were analyzed
      with neuroelectric brain imaging technique to assess cerebral oscillations
      related to treatment response. Early improvement of symptoms served as a clinical
      predictor. Treatment response was assessed after 4 weeks of antidepressant
      treatment. Responders showed more slow-frequency power in the right anterior
      cingulate cortex compared to non-responders. Slow-frequency power in this region
      was found to predict response with good sensitivity (82 %) and specificity (100
      %), while early improvement showed lower accuracy (73 % sensitivity and 65 %
      specificity). Combining both parameters did not further improve predictive
      accuracy. Pretreatment activity within the anterior cingulate cortex is related
      to antidepressive treatment response. Our results support the search for
      biological treatment response predictors using electric brain activity. This
      technique is advantageous due to its low individual and socioeconomic burden. The
      benefits of combining both, a clinically and a biologically based predictor,
      should be further evaluated using larger sample sizes.

PMID- 23873090
TI  - The effects of physical exercise in schizophrenia and affective disorders.
AB  - Affective and non-affective psychoses are severe and frequent psychiatric
      disorders. Amongst others, they not only have a profound impact on affected
      individuals through their symptomatology, but also regarding cognition, brain
      structure and function. Cognitive impairment influences patients' quality of life
      as well as their ability to work and being employed. While exercise therapy has
      been implemented in the treatment of psychiatric conditions since the days of
      Kraepelin and Bleuler, the underlying mechanisms have never been systematically
      studied. Since the early 1990s, studies emerged examining the effect of physical
      exercise in animal models, revealing stimulation of neurogenesis, synaptogenesis
      and neurotransmission. Based on that body of work, clinical studies have been
      carried out in both healthy humans and in patient populations. These studies
      differ with regard to homogenous study samples, sample size, type and duration of
      exercise, outcome variables and measurement techniques. Based on their review, we
      draw conclusions regarding recommendations for future research strategies showing
      that modern therapeutic approaches should include physical exercise as part of a
      multimodal intervention programme to improve psychopathology and cognitive
      symptoms in schizophrenia and affective disorders. 

PMID- 23873094
TI  - New bioproduction systems: from molecular circuits to novel reactor concepts in
      cell-free biotechnology.
AB  - : The last decades witnessed a strong growth in several areas of biotechnology,
      especially in fields related to health, as well as in industrial biotechnology.
      Advances in molecular engineering now enable biotechnologists to design more
      efficient pathways in order to convert a larger spectrum of renewable resources
      into industrially used biofuels and chemicals as well as into new pharmaceuticals
      and therapeutic proteins. In addition material sciences advanced significantly
      making it more and more possible to integrate biology and engineering. One of the
      key questions currently is how to develop new ways of engineering biological
      systems to cope with the complexity and limitations given by the cell. The
      options to integrate biology with classical engineering advanced cell free
      technologies in the recent years significantly. Cell free protein production
      using cellular extracts is now a well-established universal technology for
      production of proteins derived from many organisms even at the milligram scale.
      Among other applications it has the potential to supply the demand for a
      multitude of enzymes and enzyme variants facilitating in vitro metabolic
      engineering. This review will briefly address the recent achievements and
      limitations of cell free conversions. Especially, the requirements for reactor
      systems in cell free biotechnology, a currently underdeveloped field, are
      reviewed and some perspectives are given on how material sciences and
      biotechnology might be able to advance these new developments in the future. 

PMID- 23873095
TI  - Food and feed enzymes.
AB  - Humans have benefited from the unique catalytic properties of enzymes, in
      particular for food production, for thousands of years. Prominent examples
      include the production of fermented alcoholic beverages, such as beer and wine,
      as well as bakery and dairy products. The chapter reviews the historic background
      of the development of modern enzyme technology and provides an overview of the
      industrial food and feed enzymes currently available on the world market. The
      chapter highlights enzyme applications for the improvement of resource
      efficiency, the biopreservation of food, and the treatment of food intolerances.
      Further topics address the improvement of food safety and food quality.

PMID- 23873096
TI  - Progress against laryngeal cancer in The Netherlands between 1989 and 2010.
AB  - Cancer of the larynx is a frequently occurring head and neck cancer in The
      Netherlands. The main risk factors are smoking and excessive alcohol consumption.
      The aim of our study was to evaluate the progress against laryngeal cancer by
      studying trends in incidence, mortality and survival in The Netherlands. All
      patients in The Netherlands Cancer Registry diagnosed with invasive primary
      squamous cell carcinoma of the larynx during the period 1989-2010 were included
      for analysis. Time trends in incidence, mortality, treatment and survival were
      described for the total group and stratified by sex and subsite: glottis,
      supraglottis and subglottis. The most frequently affected subsite for men was the
      glottis (69%) and for women the supraglottis (55%). Glottic cancer was diagnosed
      at lower stages than supraglottic cancer. Incidence and mortality rates decreased
      for males with -2.5 and -2.8% per year, respectively, but remained stable for
      women, except for an increasing mortality rate in older women (EAPC: +2.5%). Five
      year relative survival rates were stable for glottic (85%) and supraglottic (50%)
      cancer, whereas patients with high-staged cancers more often received
      radiotherapy. Multivariable analysis showed lower relative excess risks of dying
      for women, younger patients (<75 years), glottic cancer, lower stage cancer and
      those undergoing surgery. Changes in incidence and mortality rates are in line
      with changing smoking habits in The Netherlands. Declining incidence with stable
      survival rates gives rise to hope and worry at the same time. 

PMID- 23873097
TI  - Association GSTT1, GSTM1 and GSTP1 (Ile105Val) genetic polymorphisms in mothers
      with risk of congenital malformations in their children in Western Siberia: a
      case-control study.
AB  - OBJECTIVE: Polymorphisms of glutathione S-transferase (GST) genes in mothers may
      be involved in teratogenesis in their offspring. This study aims to investigate
      the association of GST genes (T1, M1 and P1) with the risk of having children
      with congenital malformations (CMs) in residents of the West Siberian region of
      Russia. METHOD: We studied 235 women with offspring's with CMs, and 273 women
      with one or more healthy children. Null genotypes of GSTM1 and GSTT1 were
      identified through multiplex real-time polymerase chain reaction, and GSTP1 gene
      (Ile105Val) polymorphism was determined through TaqMan-real-time polymerase chain
      reaction. RESULTS: The study showed that the maternal genotype GSTT1 "0/0" is
      associated with CMs in the offspring (odd ratio (OR) = 3.63, P = 5.18 * 10(-9) ).
      A significant association of the maternal genotype GSTT1 "0/0" with CMs of the
      cardiovascular system (OR = 5.03, P = 2.93 * 10(-7) ), urinary system (OR = 4.20,
      P = 3.51 * 10(-6) ) and central nervous system (OR = 4.40, P = 6.69 * 10(-5) )
      was found in the child. No association of maternal GSTM1 (del) and GSTP1
      (Ile105Val) genetic polymorphisms with CMs of the child was identified.
      CONCLUSION: Homozygous deletion of the GSTT1 gene in women of the West Siberian
      region is a risk factor for birth defects in the child.

PMID- 23873098
TI  - Target protein for Xklp2 (TPX2), a microtubule-related protein, contributes to
      malignant phenotype in bladder carcinoma.
AB  - Increasing evidence demonstrated that TPX2 was highly expressed and tightly
      associated with human tumor development and progression. However, its precise
      role in bladder carcinoma remains to be delineated. In the present study, we
      revealed the high expression of TPX2 at both mRNA and protein levels in bladder
      carcinoma tissues and cells, and TPX2 levels in pN1-3 and pT2-4 status were
      significantly higher than those in pN0 and pTa-T1 status, respectively.
      Additionally, high TPX2 level was strongly associated with pT status (P = 0.001),
      higher histological grade (P = 0.001), lymph node metastasis (P = 0.022), and
      shorter survival time (P = 0.0279). Further investigation showed that TPX2 level
      in T24 cells was markedly higher than those in 5637, J82 and RT4 cells, in which
      RT4, a well-differentiated cell line derived from bladder carcinoma with low
      grade non-invasive T0, displayed the lowest TPX2 mRNA and protein levels.
      Besides, TPX2 overexpression promoted proliferation and tumorigenicity, shortened
      cell cycle in G0/G1 phase, and suppressed cell apoptosis in T24 cells;
      conversely, TPX2 depletion exhibited opposite effects. Furthermore, TPX2
      overexpression evoked the elevation of cyclin D1 and cdk2 levels as well as
      reduction of p21 level and caspase-3 activity, whereas reversed effects were
      observed in TPX2-depleted T24 cells. Taken altogether, TPX2 may play a central
      role in the development and progression of bladder carcinoma, and thus inhibition
      of TPX2 level may be a novel strategy for therapy of the patients with bladder
      carcinoma.

PMID- 23873100
TI  - Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a meta
      analysis.
AB  - Various studies examined the relationship between human epidermal growth factor
      receptor 2 (HER-2/neu) overexpression and the clinical outcome in patients with
      ovarian cancer, but yielded conflicting results. Electronic databases updated in
      May 2013 were searched to find relevant studies. A meta-analysis was conducted
      with eligible studies which quantitatively evaluated the relationship between HER
      2/neu overexpression and survival of patients with ovarian cancer. Survival data
      were aggregated and quantitatively analyzed. We conducted a final analysis of
      3,055 patients from 20 eligible studies and evaluated the correlation between HER
      2/neu overexpression and survival in patients with ovarian cancer. Combined
      hazard ratios suggested that HER-2/neu overexpression was not associated with a
      significant impact on survival, with the hazard ratio (HR) and 95% confidence
      interval (CI) being 1.05 and 0.92-1.19, respectively, overall. When grouped
      according to the study design type, a statistically significant combined HR was
      found in retrospective studies (HR = 1.44, 95% CI 1.14-1.75) and no statistically
      significant combined HR was found (HR = 0.96, 95% CI 0.81-1.11) for prospective
      studies. HER-2/neu overexpression seems to have no significant impact on survival
      of ovarian cancer patients. However, a statistically significant combined HR was
      found in retrospective studies, but not in prospective studies.

PMID- 23873099
TI  - Twist: a molecular target in cancer therapeutics.
AB  - Twist, the basic helix-loop-helix transcription factor, is involved in the
      process of epithelial to mesenchymal transitions (EMTs), which play an essential
      role in cancer metastasis. Overexpression of Twist or its promoter methylation is
      a common scenario in metastatic carcinomas. Twist is activated by a variety of
      signal transduction pathways, including Akt, signal transducer and activator of
      transcription 3, mitogen-activated protein kinase, Ras, and Wnt signaling.
      Activated Twist upregulates N-cadherin and downregulates E-cadherin, which are
      the hallmarks of EMT. Moreover, Twist plays an important role in some
      physiological processes involved in metastasis, like angiogenesis, invadopodia,
      extravasation, and chromosomal instability. Twist also protects cancer cells from
      apoptotic cell death. In addition, Twist is responsible for the stemness of
      cancer cells and the generation of drug resistance. Recently, targeting Twist has
      gained significant interests in cancer therapeutics. The inactivation of Twist by
      small RNA technology or chemotherapeutic approach has been proved successful.
      Moreover, several inhibitors which are antagonistic to the upstream or downstream
      molecules of Twist signaling pathways have also been identified. Development of
      potential treatment strategies by targeting Twist has a great promise in cancer
      therapeutics.

PMID- 23873101
TI  - T-cell infiltration and expressions of T lymphocyte co-inhibitory B7-H1 and B7-H4
      molecules among colorectal cancer patients in northeast China's Heilongjiang
      province.
AB  - Colorectal cancer has an extremely poor prognosis due to its high rate of
      recurrence and metastasis. The present study aimed to investigate the
      correlations between the B7-H1 and B7-H4 expressions as well as the
      clinicopathological characteristics and the prognosis of patients with colorectal
      cancer. We further inferred from these findings whether T lymphocyte co
      inhibitory molecules (B7-H1 and B7-H4) led to a poor prognosis in Heilongjiang
      patients with colorectal cancer. Survival analysis revealed that the poor
      prognosis of these patients was unrelated to patient age, tumor size or
      histological grade, or lymph node metastasis, but was associated with TNM stage,
      high B7-H1 and B7-H4 expression levels. High B7-H1 and B7-H4 expressions were
      closely correlated with poor prognosis in patients with colorectal cancer. We
      speculate that the joint detection of these molecules may clinically apply for
      diagnosing and predicting poor prognosis of patients with colorectal cancer in
      northeast China's Heilongjiang province. In addition, intervention of B7-H1 and
      B7-H4 may be beneficial for enhancement of immunity in these patients. 

PMID- 23873102
TI  - Clinical significance of histone deacetylase (HDAC)-1, HDAC-2, HDAC-4, and HDAC-6
      expression in human malignant and benign thyroid lesions.
AB  - Histone deacetylases (HDACs) have been associated with human malignant tumor
      development and progression, and HDAC inhibitors are currently being explored as
      anticancer agents in clinical trials. The present study aimed to evaluate the
      clinical significance of HDAC-1, HDAC-2, HDAC-4, and HDAC-6 proteins' expression
      in human malignant and benign thyroid lesions. HDAC-1, HDAC-2, HDAC-4, and HDAC-6
      proteins' expression was assessed immunohistochemically on paraffin-embedded
      thyroid tissues obtained from 74 patients with benign and malignant thyroid
      lesions. Enhanced HDAC-2 and HDAC-6 expression was significantly more frequently
      observed in malignant, compared to benign, thyroid lesions (p = 0.0042 and p =
      0.0069, respectively). Enhanced HDAC-2, HDAC-4, and HDAC-6 expression was
      significantly more frequently observed in cases with papillary carcinoma compared
      to hyperplastic nodules (p = 0.0065, p = 0.0394, and p = 0.0061, respectively).
      In malignant thyroid lesions, HDAC-1, HDAC-4, and HDAC-6 expression was
      significantly associated with tumor size (p = 0.0169, p = 0.0056, and p = 0.0234,
      respectively); HDAC-2 expression with lymphatic and vascular invasion (p = 0.0299
      and p = 0.0391, respectively); and HDAC-4 expression with capsular invasion (p =
      0.0464). The cellular pattern of HDAC-1 and HDAC-2 distribution (nuclear vs.
      nuclear and cytoplasmic) presented a distinct discrimination between malignant
      and benign thyroid lesions (p = 0.0030 and p = 0.0028, respectively) as well as
      between papillary carcinoma and hyperplastic nodules (p = 0.0036 and p = 0.0028,
      respectively). HDAC-1, HDAC-2, HDAC-4, and HDAC-6 may be associated with the
      malignant thyroid transformation and could be considered as useful biomarkers and
      possible therapeutic targets in this neoplasia. 

PMID- 23873103
TI  - Cytoplasmic expression of the ELAV-like protein HuR as a potential prognostic
      marker in esophageal squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most frequent cancers and
      a leading cause of death from cancer in China. The human ELAV-like protein HuR
      has been found to contribute to cancer development and progression through
      stabilizing a group of cellular mRNAs of cancer-related genes. In this study, we
      investigated the expression of HuR in a cohort of ESCC patients using
      immunohistochemical staining. HuR detected in the cytoplasm of cancer cells was
      positive in 46.6% of 58 ESCC specimens; 75.9% of these specimens had nuclear
      immunoreactivity for HuR. Cytoplasmic HuR expression was higher in cancer tissues
      compared to 20 matched adjacent noncancerous tissues. A clinicopathological study
      showed that cytoplasmic HuR expression was positively associated with lymph node
      metastasis, depth of tumor invasion, and advanced stage, whereas nuclear HuR
      expression was not correlated with any clinicopathological factors. Patients
      positive for cytoplasmic HuR expression had a cumulative 5-year survival rate of
      25.3%, whereas it was 43.8% for patients negative for cytoplasmic HuR expression.
      In a multivariate analysis, cytoplasmic HuR expression was an independent
      prognostic factor, whereas nuclear positivity for HuR was not. Our results
      indicate that high cytoplasmic HuR expression is associated with positive lymph
      node metastasis, deep tumor invasion, high stage, and poor survival in ESCC.
      Thus, HuR is the first mRNA stability protein whose expression is associated with
      poor survival in esophageal cancer.

PMID- 23873104
TI  - Association between NAD(P)H:quinone oxidoreductase 1 rs1800566 polymorphism and
      risk of bladder cancer.
AB  - NAD(P)H: quinone oxidoreductase 1 (NQO1) rs1800566 (Pro187Ser) is a functional
      polymorphism which leads to a proline-to-serine amino acid substitution at codon
      187 in the NQO1 protein and enzyme activity changes. NQO1 rs1800566 polymorphism
      was implicated to be associated with a risk of bladder cancer, but published
      studies showed inconclusive results. We performed a meta-analysis of nine
      publications with a total of 2,661 cases and 2,738 controls on the association
      between NQO1 rs1800566 polymorphism and risk of bladder cancer. Data were
      extracted from those included studies, and the pooled odds ratio (OR) with the
      corresponding 95% confidence interval (95% CI) was calculated to assess the
      association. We found that there was no association between NQO1 rs1800566
      polymorphism and risk of bladder cancer under all four genetic models (Ser vs.
      Pro, OR = 1.06, 95% CI = 0.97-1.16, P = 0.21, I(2) = 31%; SerSer vs. ProPro, OR =
      1.12, 95% CI = 0.89-1.42, P = 0.33, I(2) = 44%; SerSer/ProSer vs. ProPro, OR =
      1.08, 95% CI = 0.96-1.21, P = 0.20, I(2) = 27%; SerSer vs. ProPro/ProSer, OR =
      1.06, 95% CI = 0.85-1.32, P = 0.59, I(2) = 36%). Meta-analysis of those eight
      studies from Europeans also showed that there was no association between NQO1
      rs1800566 polymorphism and risk of bladder cancer under all four genetic models
      (Ser vs. Pro, OR = 1.02, 95% CI = 0.93-1.13, P = 0.66, I(2) = 20%; SerSer vs.
      ProPro, OR = 0.99, 95% CI = 0.75-1.30, P = 0.93, I(2) = 38%; SerSer/ProSer vs.
      ProPro, OR = 1.04, 95% CI = 0.92-1.17, P = 0.55, I(2) = 6%; SerSer vs.
      ProPro/ProSer, OR = 0.98, 95% CI = 0.75-1.28, P = 0.87, I(2) = 39%). This meta
      analysis suggests that the NQO1 rs1800566 polymorphism is not associated with a
      risk of bladder cancer. Further studies with larger samples are needed,
      especially for studies in Asians and Africans.

PMID- 23873105
TI  - High plasma D-dimer level is associated with decreased survival in patients with
      lung cancer: a meta-analysis.
AB  - An elevated plasma D-dimer level indicates the activation of coagulation and
      fibrinolysis. Several studies suggested that high level of plasma D-dimer was
      associated with the prognosis of lung cancer. In the present study, we performed
      a meta-analysis to evaluate the relationship between plasma D-dimer level and the
      prognosis of lung cancer based on larger sample size. We retrieved the
      literature, assessed and selected the data, and performed the statistical
      analysis according to the RevMan 5.0 guidelines. Literature-based searching was
      guided to gather data, and fixed-effects model was used to pool the hazard ratio
      according to the test of heterogeneity. A total of seven eligible studies
      including 1,377 lung cancer patients were analyzed. Survival time was
      significantly better in patients in the low D-dimer group than those in the high
      D-dimer group (hazard ratio for high D-dimer group = 1.12; 95% confidence
      interval 1.02 to 1.23). Patients with high levels of D-dimer have a poorer
      overall survival compared with those patients with low levels of D-dimer.

PMID- 23873106
TI  - microRNA-148a suppresses human gastric cancer cell metastasis by reversing
      epithelial-to-mesenchymal transition.
AB  - MicroRNAs (miRNAs) are important regulators of gastric cancer development and
      progression. miR-148a is one of the most frequently and highly downregulated
      miRNAs in gastric cancer and is associated with advanced clinical stage and poor
      prognosis. In this study, we investigated the role of miR-148a in gastric cancer
      metastasis. Levels of miR-148a were determined by qRT-PCR in 60 gastric cancer
      samples. Cell migration and invasion assays were performed in a stably expressing
      miRNA-148a gastric cancer cell line established using a lentivirus expression
      system. Epithelial-mesenchymal transition (EMT) was evaluated using qRT-PCR and
      Western Blots to detect epithelial marker E-cadherin and mesenchymal marker,
      vimentin. Luciferase reporter assays were used to identify downstream targets and
      biological function of miR-148a. Gastric cancer tissue had significantly lower
      expression of miR-148a compared to non-tumor tissue. Low miR-148a levels were
      associated with lymph node metastasis, N stage, and blood vessel invasion. miR
      148a overexpression inhibited metastasis of gastric cancer cells. miR-148a
      overexpression also downregulated vimentin expression and upregulated E-cadherin
      expression, suggesting that miR-148a inhibited EMT. Finally, the SMAD2 gene was
      identified as the direct and functional target of miR-148a. MiR-148a suppresses
      gastric cancer metastasis and EMT, likely via SMAD2. Restoration of miR-148a
      expression could have important implications in gastric cancer therapy. 

PMID- 23873107
TI  - The association of matrix metalloproteinase-1 genetic polymorphism (-1607 1G>2G)
      with colorectal cancer: a meta-analysis.
AB  - Several case-control studies on the relation between matrix metalloproteinase
      (MMP)-1 gene -1607 1G>2G polymorphism and colorectal cancer do not have similar
      conclusions. The previous two meta-analyses focusing on the same issue also were
      inconsistent. To further evaluate the relation between the MMP-l gene
      polymorphism and colorectal cancer, we selected eight case-control studies
      related to MMP-1 gene polymorphism and colorectal cancer by searching MEDLINE,
      Embase, CANCERLIT, American Association for Cancer Research, Chinese Biomedical
      Literature Database, Chinese CNKI, and Wanfang database. Q test and I (2) test
      were used to test the heterogeneity. We utilized the random effects model to
      calculate the odds ratio (OR), 95% confidence interval (CI), and the overall
      effect of P value using the RevMan 5.2 software. The present study included 1,403
      patients with colorectal cancer and 1,754 healthy control subjects. Both -1607
      2G/2G genotype carriers [OR = 1.59, 95 % CI (1.27-2.01); P < 0.001] and the -1607
      2G allele carriers [OR = 1.26, 95% CI (1.05-1.51); P = 0.01] were found to have
      an increased risk of colorectal cancer. Therefore, we concluded that MMP-1 -1607
      1G>2G polymorphism was associated with colorectal cancer.

PMID- 23873108
TI  - Regulation of BMI1 Polycomb gene expression in histological grades of invasive
      ductal breast carcinomas and its correlation with hormone receptor status.
AB  - BMI1 is the first functional mammalian Polycomb group (PcG) proto-oncogene
      involved in multiple biological processes. Regulation of B cell-specific Moloney
      murine leukaemia virus integration site 1 (BMI1) expression with increase in
      histological grades of breast carcinoma in correlation with hormone receptor
      status was studied in 60 Indian breast cancer patient's formalin-fixed paraffin
      embedded tissue blocks. Relative expression of BMI1 was studied using real-time
      PCR. Immunohistochemistry explained the distribution of hormone receptor markers.
      Correlation of BMI1 gene expression with oestrogen receptor, progesterone
      receptor (PR) and human epidermal growth factor receptor 2/neu status was
      analysed using Hex-protein docking tool. The hormone receptor expression was
      reduced with increasing grades of breast tumour. BMI1 gene expression was
      downregulated (real-time polymerase chain reaction analysis). Docking analysis
      explained the correlation between BMI1 and PR expression. BMI1 gene was co
      regulated (down) with PR in the invasive ductal breast carcinoma with relative
      progression explicating it a diagnostic biomarker for ductal carcinoma of the
      breast. 

PMID- 23873110
TI  - Significant association between XRCC3 C241T polymorphism and increased risk of
      hepatocellular carcinoma: a meta-analysis.
AB  - Many studies were published to examine the association between XRCC3 C241T
      polymorphism and hepatocellular carcinoma risk, but their results were
      inconsistent. To assess the association between XRCC3 C241T polymorphism and
      hepatocellular carcinoma risk more precisely, a meta-analysis was performed.
      PubMed, Embase and Wanfang databases were searched for relevant case-control
      studies. Data were extracted, and the pooled odds ratios (OR) with 95 %
      confidence intervals (95% CI) were calculated. Finally, seven studies comprising
      2,288 cases with hepatocellular carcinoma and 3,249 controls were included into
      the meta-analysis. Overall, there was an obvious association between XRCC3 C241T
      polymorphism and increased risk of hepatocellular carcinoma (TT versus CC: OR =
      3.31, 95% CI 1.52-7.19, P = 0.003; TT versus CC/CT: OR = 3.31, 95% CI 1.81-6.06,
      P < 0.001). After adjusting for heterogeneity, there was still an obvious
      association between XRCC3 C241T polymorphism and increased risk of hepatocellular
      carcinoma (TT versus CC: OR = 1.92, 95 % CI 1.13-3.26, P = 0.016; TT versus
      CC/CT: OR = 2.10, 95% CI 1.25-3.55, P = 0.005). Overall, there is a significant
      association between XRCC3 C241T polymorphism and increased risk of hepatocellular
      carcinoma. Further studies are needed to further assess the association in
      Caucasians.

PMID- 23873109
TI  - The cyclin D1 (CCND1) G870A polymorphism and lung cancer susceptibility: a meta
      analysis.
AB  - Several studies have investigated the association between Cyclin D1 (CCND1) G870A
      genetic polymorphism and lung cancer susceptibility, but the results were
      inconclusive. The aim of this meta-analysis was to summarize available evidence
      for such a relationship. The reviewers made use of MEDLINE, EMBASE, and BIOSIS
      databases. The relevant data were independently extracted by two reviewers. The
      odds ratio (OR) with 95% confidence interval (CI) was selected as the principal
      outcome measure. The heterogeneity test, the publication bias test, and the
      sensitivity analysis were performed. Overall, a total of 10 case-control studies
      were included. Our meta-analysis indicated that CCND1 G870A genetic polymorphism
      was a risk factor for lung cancer under homozygote model (OR = 1.18; 95% CI =
      1.02, 1.37), recessive model (OR = 1.21; 95% CI = 1.03, 1.41), and allele model
      (OR = 1.11; 95% CI = 1.02, 1.21). In the subgroup analysis by source of
      ethnicity, a statistical increase of lung cancer risk was found among Asian
      groups for allele model (OR = 1.11; 95% CI = 1.01-1.22). The present meta
      analysis suggests that CCND1 G870A polymorphism may be a risk factor for lung
      cancer. Besides, allele A may contribute to increased lung cancer risk.

PMID- 23873111
TI  - Altered expression of ERs, aromatase, and COX2 connected to estrogen action in
      type 1 endometrial cancer biology.
AB  - In order to study estrogen-driven microenvironment associated with type 1
      endometrial carcinoma, we evaluated estrogen receptors (ERs), aromatase, and
      cyclooxygenase II (COX2) molecular and immunohistochemical profiles with
      correlation to clinicopathological features. We investigated aromatase, ERalpha,
      ERbeta, and COX2 expression at the mRNA and protein levels using quantitative
      real-time PCR and immunohistochemical method in 51 endometrial carcinomas and 16
      normal endometria. All the studied tumors, as well as normal endometria,
      expressed ERalpha, ERbeta, and COX2 mRNAs. Five endometrial carcinoma tissues and
      one normal endometrium showed no aromatase mRNA expression. The majority of
      tumors expressed ERalpha (82%), aromatase (80%), and COX2 (88%) proteins. Forty
      one percent of the studied tumors were ERbeta-negative. ERalpha and ERbeta showed
      significantly decreased mRNA and protein expression levels in endometrial
      carcinoma as compared to normal endometrium. An opposite trend was shown for COX2
      and aromatase proteins. ERalpha expression correlated positively with COX2
      expression at both mRNA and protein levels (P < 0.005, r = 0.398; P < 0.0005, r =
      0.510, respectively). There was also a positive correlation between COX2 and
      aromatase expression in cancer tissue (P < 0.002, r = 0.433 for transcriptional
      level; P < 0.0005, r = 0.614 for protein level). We observed positive
      correlations between ERbeta and ERalpha, as well as between ERbeta and COX2 at
      the transcriptional level only (P < 0.0005, r = 0.644; P < 0.002, r = 0.444,
      respectively). Negative correlations were found between pT category of primary
      tumor and levels of ERalpha and ERbeta transcripts (P < 0.02, r = -0.332; P <
      0.02, r = -0.348, respectively). A negative association between ERbeta and the
      International Federation of Gynecology and Obstetrics (FIGO) staging was also
      found. The growth of EC1 with the presence of ERalpha and overexpression of
      aromatase and COX2 is dependent on estrogens. We believe that ERbeta may be
      considered as a potential marker in the progression of disease in endometrial
      cancer patients.

PMID- 23873112
TI  - Effect of HSP90 inhibitor in pheochromocytoma PC12 cells: an experimental
      investigation.
AB  - This study aims to investigate whether the expression of heat shock protein 90
      (HSP90) is associated with the malignant pheochromocytoma (PHEO) and the effects
      of 17-allylamino-17-demethoxygeldanamcyin (17-AAG) on the expression of vascular
      endothelial growth factor (VEGF) in PHEO cell line PC12. The expression of HSP90
      was investigated in 38 paraffin-embedded samples of PHEO patients using
      immunohistochemistry. The time and concentration effects of 17-AAG were
      investigated in PHEO PC12 cells. Cell proliferation was measured by MTT assay and
      cell counting. Apoptosis was detected by flow cytometry. Positive staining for
      HSP90 was found in 14 of 17 malignant (82.35%) and in 5 of 21 (23.81%) benign
      PHEOs. There existed a significant statistical difference between the malignant
      group and the benign ones (P < 0.001). 17-AAG inhibited the proliferation of HCC
      cells in a time- and concentration-dependent manner. The apoptosis rates of PC12
      cells after treatment with 0.1 MUmol/L for 6, 12, 24, and 48 h were significantly
      higher than that in blank control group. 17-AAG significantly downregulated VEGF
      165 protein level in PC12 cells. This study has confirmed that the specific HSP90
      inhibitor 17-AAG can play a therapeutic role in malignant PHEO treatment, and
      HSP90 qualifies as a promising new target in malignant PHEO.

PMID- 23873113
TI  - Surface chemistry of gold nanorods: origin of cell membrane damage and
      cytotoxicity.
AB  - We investigated how surface chemistry influences the interaction between gold
      nanorods (AuNRs) and cell membranes and the subsequent cytotoxicity arising from
      them in a serum-free cell culture system. Our results showed that the AuNRs
      coated with cetyl trimethylammonium bromide (CTAB) molecules can generate defects
      in the cell membrane and induce cell death, mainly due to the unique bilayer
      structure of CTAB molecules on the surface of the rods rather than their charge.
      Compared to CTAB-capped nanorods, positively charged polyelectrolyte-coated, i.e.
      poly(diallyldimethyl ammonium chloride) (PDDAC), AuNRs show improved
      biocompatibility towards cells. Thus, the present results indicate that the
      nature of surface molecules, especially their packing structures on the surface
      of AuNRs rather than surface charge, play a more crucial role in determining
      cytotoxicity. These findings about interfacial interactions could also explain
      the effects of internalized AuNRs on the structures or functions of organelles.
      This study will help understanding of the toxic nature of AuNRs and guide
      rational design of the surface chemistry of AuNRs for good biocompatibility in
      pharmaceutical therapy. 

PMID- 23873114
TI  - Cerebral, renal, and splanchnic tissue oxygen saturation values in healthy term
      newborns.
AB  - OBJECTIVE: To determine cerebral regional tissue oxygen saturation (CrSO2), renal
      regional tissue oxygen saturation (RrSO2), and splanchnic regional tissue oxygen
      saturation (SrSO2) values in healthy term infants. STUDY DESIGN: Near-infrared
      spectroscopy was used to simultaneously measure CrSO2, RrSO2, and SrSO2
      continuously for a 1-hour period on the first and second days of life. RESULTS: 
      A total of 41 subjects were monitored out of which complete data were available
      for 38 subjects. Mean CrSO2 was 78.2  +/- 7.9% on first day; 78.3 +/- 6.1% on
      second day (p = 0.95). Mean RrSO2 was 92.1 +/- 5.3% on first day; 88.9 +/- 5.9%
      on second day (p < 0.01). Mean SrSO2 was 69.9 +/- 12.1% on first day and 75.3 +/-
      12.4% on second day (p = 0.02). CONCLUSION: There appears to be consistency in
      rSO2 values in healthy newborns. CrSO2 was similar on both days. Differences
      observed in RrSO2 and SrSO2 between days may represent a shift in somatic blood
      flow distribution taking place during the first day of life.

PMID- 23873115
TI  - American college of obstetricians and gynecologists practice bulletins:
      ascertaining their citation, influence, and utilization.
AB  - OBJECTIVE: To ascertain the influence and utilization of the American College
      Obstetricians and Gynecologists practice bulletins (PBs) by measuring their
      citations in three different search tools. STUDY DESIGN: PBs in obstetrics (OB
      PBs) and gynecology (GYN-PBs) published from September 1998 to December 2009 were
      identified. PubMed, Ovid MEDLINE, and Web of Science were utilized to determine
      how often PBs were cited. The citations were quantified by three parameters, most
      citations, highest citation rate, and highest impact factor. RESULTS: The OB-PB
      with the most citations (125) was PB no. 33 (Diagnosis and Management of
      Preeclampsia and Eclampsia), highest citation rate (44) was PB no. 101
      (Ultrasonography in Pregnancy), highest OBGYN impact factor (4.39) was PB no. 71
      (Episiotomy), and highest non-OBGYN impact factor (53.49) was PB no. 38
      (Perinatal Care at Threshold of Viability). The GYN-PB with the highest citation
      rate (103) was PB no. 109 (Cervical Cytology Screening), highest OBGYN impact
      factor (3.85) was PB no. 103 (Hereditary Breast and Ovarian Cancer Syndrome), and
      highest non-OBGYN impact factor (20.89) was PB no. 35 (Cervical Carcinoma).
      CONCLUSIONS: No one PB had the most citations, highest citation rate, and highest
      impact factor.

PMID- 23873116
TI  - Second trimester amniotic fluid is reliably fern positive and alpha1
      microglobulin positive: dispelling a labor deck myth.
AB  - OBJECTIVE: Many physicians erroneously believe and have propagated the "myth"
      that a second trimester amniotic fluid sample will not fern. We attempted to
      redemonstrate ferning and to demonstrate the efficacy of an assay for alpha1
      microglobulin in second trimester amniotic fluid samples. STUDY DESIGN: Amniotic
      fluid samples were collected from women undergoing routine genetic amniocentesis
      between 15 and 26 weeks. A total of 97 samples of second trimester amniotic fluid
      were placed on slides and examined for ferning at 5 and 10 minutes. An alpha1
      microglobulin assay was performed on each sample. Data were recorded and
      reported. RESULTS: Approximately 93% of samples were fern positive at 5 minutes
      and 100% were fern positive at 10 minutes. All samples were alpha1-microglobulin
      positive. CONCLUSION: Pure amniotic fluid is reliably fern and alpha1
      microglobulin positive in the second trimester. Republication of data only
      available in pre-online sources will benefit physicians and patients.

PMID- 23873117
TI  - Acidemia versus hypercapnia and risk for severe intraventricular hemorrhage.
AB  - In extremely low birth weight (ELBW) infants, levels of hypercapnia (Paco 2) > 60
      mm Hg are considered a risk factor for severe intraventricular hemorrhage (IVH).
      Since cerebral vasoreactivity depends on arterial pH (apH) rather than Paco 2, we
      hypothesize that the role of mild-to-moderate hypercapnia (45-60 mm Hg) in the
      occurrence of severe IVH is modulated by the metabolic component of acid-base
      status. ELBW infants (n = 580, born < 28 wk gestation, and BW < 1,000 g) were
      separated into "high-base deficit (BD)" (n = 291) and "low-BD" (n = 289) groups
      if infants' median BD were > 4 mEq/L or <=4 mEq/L, respectively. Rates of severe
      IVH were higher in "high-BD" (16%) than "low-BD" (9%) group. Although adjusted
      risk for severe IVH increased with higher Paco 2 and higher BD, apH was the sole
      predictor of severe IVH. In ELBW infants, higher degree of acidemia, rather than
      hypercapnia per se, during the first 48 hours of life, is associated with higher
      occurrences of severe IVH. 

PMID- 23873118
TI  - Variation in the alpha(2A) adrenoceptor gene and the effect of dexmedetomidine on
      plasma insulin and glucose.
AB  - OBJECTIVES: Sympathetic activation inhibits insulin secretion through activation
      of pancreatic alpha(2)A adrenoreceptors (alpha(2A)ARs). A common genetic
      alpha(2A)AR variant (rs553668) is associated with impaired insulin secretion.
      alpha(2A)R agonists would be expected to decrease insulin secretion, but their
      effects on glucose homeostasis in humans are poorly characterized. We examined
      the hypotheses that the selective alpha(2A)R agonist, dexmedetomidine, decreases
      plasma insulin levels and increases plasma glucose levels in humans and that
      these effects are modified by genetic alpha(2A)AR variants. METHODS: Healthy,
      fasting, White (n=31) and Black (n=33) participants aged between 18 and 45 years
      received three sequential infusions of placebo (normal saline) at 30-min
      intervals, followed by three infusions of dexmedetomidine (0.1, 0.15, and 0.15
      mcg/kg). Plasma insulin and glucose concentrations were measured at baseline and
      after the administration of placebo and dexmedetomidine. We genotyped ADRA2A
      rs553668 and rs2484516, which characterize haplotypes 4 and 4b, respectively.
      RESULTS: Dexmedetomidine decreased fasting insulin concentrations by 37%, from a
      median value after placebo administration of 7.9 MUU/ml (interquartile range: 6.0
      12.6) to 4.9 MUU/ml (interquartile range: 3.5-7.9; P<0.001). Plasma glucose
      concentrations increased from 76+/-6 to 79+/-7 mg/dl (P<0.001). The rs2484516
      variant allele was associated with higher baseline insulin concentrations before
      (P=0.001) and after adjustment for potential confounders (P=0.014) and a greater
      decrease in insulin concentration after dexmedetomidine administration (P=0.016),
      which was no longer significant after adjustment for baseline concentrations and
      other confounders (P=0.58). CONCLUSION: Low-dose dexmedetomidine decreased plasma
      insulin concentration and mildly increased plasma glucose concentration in
      healthy fasting individuals. The ADRA2A genetic variation may affect baseline
      insulin concentrations and thus the insulin decrease after dexmedetomidine
      administration.

PMID- 23873119
TI  - A gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes
      influences the renal clearance of metformin.
AB  - OBJECTIVE: The aim of this study was to determine the association between the
      renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the
      single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the
      relevance of the gene-gene interactions between this SNP and (a) the promoter SNP
      g.-66T>C (rs2252281) in MATE1 and (b) the OCT1 reduced-function diplotypes.
      METHODS: Fifty healthy volunteers genotyped for the c.808G>T were enrolled in the
      study. The distribution was 25 GG, 20 GT, and 5 TT volunteers. The
      pharmacokinetics of a 500 mg single oral dose of metformin was studied. RESULTS:
      When analyzed alone, the c.808 (G>T) affected neither the CL(renal) nor the
      secretory clearance (CL(sec)) of metformin. However, both CL(renal) and CL(sec)
      were increased for the volunteers with minor alleles in c.808 (G>T) who were also
      homozygous for the reference variant g.-66T>C: CL(renal): GG, GT, and TT: 28.1,
      34.5, and 44.8 l/h (P = 0.004), respectively and CL(sec): GG, GT, and TT: 21.4,
      27.8, and 37.6 l/h (P = 0.005), respectively. In the volunteers with minor
      alleles in c.808 (G>T) who were also heterozygous for g.-66T>C, both CL(renal)
      and CL(sec) were found to be reduced (P < 0.028) when compared with volunteers
      with minor alleles in c.808 (G>T) carrying the g.-66T>C reference genotype.
      CONCLUSION: We report counteracting effects of the c.808 (G>T) and g.-66T>C on
      the renal elimination of metformin. When adjusted for the genetic variation g.
      66T>C, our results suggest that c.808 (G>T) could have a dominant genotype to
      phenotype correlation.

PMID- 23873120
TI  - Meta-analysis and systematic review of the effect of the donor and recipient
      CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver transplantation.
AB  - OBJECTIVE: A meta-analysis was carried out of published studies on the effect of
      the CYP3A5 6986A>G polymorphism in liver donors and transplant recipients on
      tacrolimus pharmacokinetics. METHODS: Cohort studies that evaluated the
      relationship between the CYP3A5 polymorphism in liver donors and transplant
      recipients and tacrolimus, trough blood concentration normalized for the daily
      dose (C) per kilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to 1 year after
      transplantation, were included. Data were not restricted by patient age or the
      language or journal of publication. A literature search was conducted using the
      Cochrane Library, MEDLINE, EMBASE, and grey literature, and articles published up
      to 24 April 2013 were selected. Data were pooled (random-effects model), and the
      results were expressed as the mean difference of the corresponding C/D ratios and
      95% confidence intervals. RESULTS: Six studies involving donor genotypes (254
      patients) and four involving recipient genotypes (180 patients) were ultimately
      included. The meta-analysis showed the C/D ratio to be significantly higher in
      recipients with nonexpresser donor variants at all time points. In recipients,
      the variant did not influence the C/D ratio. CONCLUSION: The presence of the
      CYP3A5 6986A>G polymorphism in the donor affects tacrolimus pharmacokinetics in
      the recipient, although only the evidence available for the first month after
      transplantation was of adequate quality for demonstrating a significant
      difference. The evidence provided here shows no effect of the recipient genotype;
      however, the quality of the evidence was low, thereby precluding the drawing of
      firm conclusions.

PMID- 23873121
TI  - Role of Akt signaling pathway in delayed cerebral vasospasm after subarachnoid
      hemorrhage in rats.
AB  - BACKGROUND: Akt plays an important role in cell survival, proliferation,
      apoptosis and other activities. It also has been involved in maintaining smooth
      muscle cell contraction phenotypes in vitro and in vivo. Recent studies have
      focused on the inhibition of Akt in acute vasospasm and neuronal apoptosis after
      subarachnoid hemorrhage (SAH). However, its role in delayed cerebral vasospasm
      (DCVS) has not been reported. METHODS: In this study, using a "two-hemorrhage"
      rat model of SAH, we examined the expression of p-Akt and the formation of
      vasospasm in the basilar arteries. To investigate the possible role of Akt in
      phenotypic switching, we performed immunohistochemical staining to examine
      expressions of SMalpha-actin and proliferating cell nuclear antigen (PCNA),
      markers of smooth muscle phenotypic switching. RESULTS: We found that the basilar
      arteries exhibited vasospasm after SAH and that vasospasm became most severe on
      day 7 after SAH. Elevated protein expression of p-Akt was detected 4 days after
      SAH induction, peaked on day 7, and recovered on day 21, which was in a parallel
      time course to the development of DCVS. Moreover, results of immunohistochemical
      staining revealed enhanced expression of PCNA but gradual reduction in expression
      of SMalpha-actin from day 1 to day 7 after SAH; then, the expressions of PCNA and
      SMalpha-actin gradually recovered until day 21. CONCLUSIONS: These results
      support a novel mechanism in which the Akt signaling pathway plays an important
      role in the proliferation of smooth muscle cells (SMCs) rather than inducing
      phenotype switching in basilar arteries, which promotes the development of DCVS
      after SAH.

PMID- 23873122
TI  - Clinical analysis of primary melanotic ependymoma in the central nervous system:
      case series and literature review.
AB  - BACKGROUND: Melanotic ependymoma (ME) is an extremely rare subset of ependymoma
      characterized by cytoplasmic and extracellular deposition of melanin, with no
      case series having been reported to date. The aim of this study was to analyze
      the clinical manifestations, pathological and radiological features, treatment,
      and follow-up data, and to discuss the diagnosis, management and prognosis of ME.
      METHODS: We retrospectively reviewed the clinical and imaging data of six
      patients with primary ME. The diagnosis was based on radiological and
      pathological criteria. All the patients were treated surgically with gross total
      resection. The preoperative and postoperative neurological states of the patients
      were analyzed. All the follow-up data were obtained from office visits, and the
      long-term outcomes are presented and discussed. RESULTS: Patients presented with
      nonspecific symptoms. On magnetic resonance imaging (MRI), although a
      characteristic signal variation could be found reflecting the melanin component,
      individual appearances varied widely and were related to the content and
      distribution of melanin in the ME lesions. The characteristic ependymoma-related
      pathological appearance and specific immunostaining for glial fibrillary acidic
      protein and antimelanoma monoclonal antibody were revealed. During a mean follow
      up period of 46.8 months, no local recurrences or distant metastases were
      observed. CONCLUSIONS: The accurate diagnosis of ME depends on pathology. The
      histological grading used for ependymoma can be applied. Most MEs have a
      relatively benign course. Complete surgical resection alone is the treatment of
      choice for low-grade MEs, and the outcome may be favorable. Postoperative
      adjuvant radiotherapy can be considered for lesions with histologically
      anaplastic features.

PMID- 23873123
TI  - Long-term results of microvascular decompression for trigeminal neuralgia and
      hemifacial spasms according to preoperative symptomatology.
AB  - BACKGROUND: Microvascular decompression (MVD) is currently used in several
      centres for the treatment of trigeminal neuralgia (TN) and hemifacial spasms
      (HFS). How long-term results relate to the preoperative symptoms still needs to
      be documented. The primary aim of this study was to assess long-term results of
      MVD for TN and HFS, as related to the types of preoperative symptoms. METHODS: We
      performed a retrospective study including all first-time MVDs for TN and HFS done
      during the 11-year period (1999-2009) in the Department of Neurosurgery, The
      National Hospital (Rikshospitalet), Oslo. The patients were categorized depending
      on the pre-operative symptomatology. RESULTS: The study population includes 303
      first-time procedures performed by the senior author (PKE), 243 TN patients (65 %
      TN without constant pain and 35 % TN with constant pain) and 60 HFS patients (95
      % typical HFS and 5 % atypical HFS). The patients were followed for a mean 71
      months (range, 14-147). In both the TN and HFS patients, MVD caused lasting
      symptom relief in a high proportion of patients, including patients with atypical
      symptoms. CONCLUSION: After MVD for TN and HFS, regardless of preoperative
      symptoms, lasting relief is observed in a high proportion of patients, with a
      favorable complication profile.

PMID- 23873124
TI  - Tissue dissection before direct manipulation to the pathology with pulsed laser
      induced liquid jet system in skull base surgery--preservation of fine vessels and
      maintained optic nerve function.
AB  - BACKGROUND: Most difficulties in skull base tumor removal are generally caused by
      adhesion of feeding arteries to the vital structures and cranial nerves. Water
      jet technology provides tissue dissectability with preservation of fine blood
      vessels both in experimental and clinical situations. However problems still
      remain regarding whether tumor removal with preservation of peripheral nerve
      function is possible or not. This clinical investigation evaluated functional
      preservation of peripheral nerves and dissectability with a newly developed
      pulsed laser-induced liquid jet (LILJ) system under intraoperative
      electrophysiological monitoring. METHODS: The LILJ system was used to treat 21
      patients with skull base tumors manifesting as severe visual disturbance through
      the extended transsphenoidal approach. The LILJ system consists of a bayonet
      shaped catheter incorporating a jet generator, and total weight is around 7 g.
      Intraoperative visual evoked potential (VEP), and pre/postoperative conventional
      visual assessments were investigated. RESULTS: Precise dissections of the tumor
      were obtained, resulting in gross total removal in 19 of 21 patients. Two
      patients with meningiomas with tight adhesion to the origin of the
      lenticulostriate arteries had small remnants. Of the 21 patients, 16 showed
      immediate improvement on intraoperative VEP, 2 had no change, and 3 had prolonged
      latency, which required intermittent suspension of procedure. A total of 20
      patients and 40 eyes showed good recovery at discharge, and all patients
      evaluated had recovered good visual status. CONCLUSIONS: The LILJ system can
      achieve safe and optimal removal with functional preservation of optic nerves,
      probably because of the high resistance of the arachnoidal sheath and fine
      vascular tissue.

PMID- 23873126
TI  - Estimating Human Cases of Avian Influenza A(H7N9) from Poultry Exposure.
AB  - In March 2013 an outbreak of avian influenza A(H7N9) was first recognized in
      China. To date there have been 130 cases in human, 47% of which are in men over
      the age of 55.The influenza strain is a novel subtype not seen before in humans;
      little is known about zoonotic transmission of the virus, but it is hypothesized
      that contact with poultry in live bird markets may be a source of exposure. The
      purpose of this study is to estimate the transmissibility of the virus from
      poultry to humans by estimating the amount of time shoppers, farmers, and live
      bird market retailers spend exposed to poultry each day. Results suggest that
      increased risk among older men is not due to greater exposure time at live bird
      markets. 

PMID- 23873125
TI  - Surgical treatment of typical peripheral schwannomas: the risk of new
      postoperative deficits.
AB  - BACKGROUND: Although peripheral schwannomas can be resected without postoperative
      neurological complications, surgeons must anticipate the possibility that new
      neurological deficits could develop. In order to evaluate the risk of
      neurological complications in the surgical treatment of these tumours, we
      performed a retrospective review of cases involving schwannomas in the
      extremities, as well as an analysis of the related literature. METHOD: We
      reviewed a combined series of 72 schwannomas from the extremities presenting for
      surgical excision. Meticulous analysis of the files was undertaken, searching for
      pre-operative findings that could be more frequent in patients with surgical
      complications. The incidence, severity, and transitory nature of post-operative
      complications in our series was observed and compared against the literature.
      RESULTS: Eleven patients (15.2 %) developed new neurological deficits after
      surgery: sensory disturbance in seven cases, motor weakness in three, and a
      single wound hematoma. Most of these complications were temporary. Statistical
      analysis demonstrated a positive relationship between the presence of
      complications and both patient age under 50 years (p = 0.02) and tumours greater
      than 3 cm in greatest diameter (p = 0.02). CONCLUSIONS: Although relatively
      infrequent, the potential for novel post-operative deficits after the surgical
      treatment of peripheral schwannomas does exist and should be included during pre
      operative counseling.

PMID- 23873127
TI  - Experimental and theoretical studies of CO2 spectra for planetary atmosphere
      modelling: region 600-9650 cm(-1) and pressures up to 60 atm.
AB  - Extensive experimental studies of room-temperature carbon dioxide absorption
      coefficients are reported for a wide range of wavenumbers and pressures requested
      in atmospheric spectra modelling. The quality of measurements is optimised by the
      use of two complementary setups with long- and short-path optical cells for low
      and high gas densities, respectively. The recorded spectra provide a
      representative picture of band-shape evolutions from gaseous to nearly liquid
      phases of CO2 and enable a theoretical analysis of line-mixing effects. Various
      kinds of vibrational bands (Sigma<-Sigma, Pi<-Sigma as well as Pi<-Pi
      transitions) are modelled using a specific, non-Markovian in the general case,
      approach of Energy-Corrected Sudden type which is based on the symmetric
      relaxation matrix and, in contrast to the standard ECS model used for infrared
      absorption calculations, ensures automatically the fundamental relations of
      detailed balance and double-sided sum rules. Moreover, this method properly
      accounts for the vibrational angular momenta of the initial and final molecular
      states and allows including Coriolis resonances via the usual Herman-Wallis
      factors in the dipole transition moments. With a set of ECS parameters previously
      obtained for isotropic and anisotropic Raman spectra modelling, completely
      neglected imaginary part of the relaxation operator and a simple change in the
      tensorial rank to get the dipole absorption case in the working formulae, the
      computed spectra reproduce quite correctly the vibrotational band shapes up to 20
      amagat without any additional parameter. An empirical correction factor
      tentatively introduced to account globally for the Coriolis effects on the
      relaxation matrix leads to better matches with high-density band shapes but its
      role merits further studies with an accurately modelled imaginary part of the
      relaxation matrix. 

PMID- 23873128
TI  - Effects on glucagon-like peptide-1 secretion by distal ileal administration of
      nutrients.
AB  - BACKGROUND: The aim of this study was to investigate the effects of nutrients
      (glucose, fat, and amino acid) on glucagon-like peptide-1 (GLP-1) secretion by
      the L cell in the distal ileum and insulin level in peripheral blood. METHODS:
      Ninety-six Wistar rats were randomly allocated into 12 groups, with 8 rats in
      each group: glucose-10 cm, glucose-15 cm, glucose-20 cm, fat-10 cm, fat-15 cm,
      fat-20 cm, amino acid-10 cm, amino acid-15 cm, amino acid-20 cm, control-10 cm,
      control-15 cm, and control-20 cm. Blood samples were collected at 0, 30, 60, 90,
      and 120 min after in vivo distal ileal perfusion of nutrients or normal saline
      (control groups). Blood glucose level was assessed by a handheld glucometer.
      Plasma GLP-1 and insulin level were evaluated by ELISA. GLP-1 level was also
      evaluated by immunohistochemistry analysis of GLP-1 expression in ileal mucosa
      and scanning electron microscope analysis of ultrastructural changes of L cells.
      RESULTS: Under administration of nutrients in the distal ileum of equal length,
      GLP-1 levels were greatest for fat, then glucose, and then amino acid (the peak
      concentration of GLP-1 in the fat-10 cm group, the glucose-10 cm group, the amino
      acid-10 cm group, and the control-10 cm group was 29.76 +/- 1.32, 28.54 +/- 1.29,
      26.30 +/- 1.26, and 22.52 +/- 1.22 pmol/L, respectively, with p < 0.05). Under
      administration of nutrients in the distal ileum of equal length, insulin levels
      were also greatest for fat, then glucose, and then amino acid (the peak
      concentration of insulin in the fat-10 cm group, the glucose-10 cm group, the
      amino acid-10 cm group, and the control-10 cm group was 30.10 +/- 1.33, 27.17 +/-
      1.27, 22.98 +/- 1.31, and 12.40 +/- 1.11 mU/L, respectively, with p < 0.05).
      Under administration of the same nutrients, the longer the distal ileum was
      stimulated, the greater the GLP-1 and insulin levels. CONCLUSIONS: Long distal
      ileal administration of fat more efficiently stimulated GLP-1 secretion,
      resulting in enhanced insulin secretion.

PMID- 23873129
TI  - Ultrasound-enhanced delivery of morpholino with Bubble liposomes ameliorates the
      myotonia of myotonic dystrophy model mice.
AB  - Phosphorodiamidate morpholino oligonucleotide (PMO)-mediated control of the
      alternative splicing of the chloride channel 1 (CLCN1) gene is a promising
      treatment for myotonic dystrophy type 1 (DM1) because the abnormal splicing of
      this gene causes myotonia in patients with DM1. In this study, we optimised a PMO
      sequence to correct Clcn1 alternative splicing and successfully remedied the
      myotonic phenotype of a DM1 mouse model, the HSALR mouse. To enhance the
      efficiency of delivery of PMO into HSALR mouse muscles, Bubble liposomes, which
      have been used as a gene delivery tool, were applied with ultrasound exposure.
      Effective delivery of PMO led to increased expression of Clcn1 protein in
      skeletal muscle and the amelioration of myotonia. Thus, PMO-mediated control of
      the alternative splicing of the Clcn1 gene must be important target of antisense
      therapy of DM1.

PMID- 23873130
TI  - Early exercise rehabilitation of muscle weakness in acute respiratory failure
      patients.
AB  - Acute respiratory failure patients experience significant muscle weakness, which
      contributes to prolonged hospitalization and functional impairments after
      hospital discharge. Based on our previous work, we hypothesize that an exercise
      intervention initiated early in the intensive care unit aimed at improving
      skeletal muscle strength could decrease hospital stay and attenuate the
      deconditioning and skeletal muscle weakness experienced by these patients. 

PMID- 23873131
TI  - Exercise and nutrition to target protein synthesis impairments in aging skeletal
      muscle.
AB  - The loss of skeletal muscle size and function with aging and sarcopenia may be
      related, in part, to an age-related muscle protein synthesis impairment. In this
      review, we discuss to what extent aging affects skeletal muscle protein synthesis
      and how nutrition and exercise can be used strategically to overcome age-related
      protein synthesis impairments and slow the progression of sarcopenia. 

PMID- 23873132
TI  - Potential role of branched-chain amino acid catabolism in regulating fat
      oxidation.
AB  - Insulin-resistant or obese individuals have increased serum branched-chain amino
      acid (BCAA) levels. Recent findings relate increased BCAA catabolism to increased
      fatty acid oxidation and better metabolic health in physically active
      individuals. We hypothesize that, via glyceroneogenesis, BCAA catabolism mediates
      increased constitutive use of fatty acids for beta-oxidation in subjects with
      increased inherent or acquired aerobic capacity both during exercise and at rest.

PMID- 23873134
TI  - What predicts intention-behavior discordance? A review of the action control
      framework.
AB  - The physical activity intention-behavior gap is a focus of considerable research.
      The purpose of this article is to overview contemporary evidence for predictors
      of this intention-behavior discordance using the action control framework
      developed in our laboratories. We propose the hypothesis that intention-behavior
      discordance is from motivational (affective attitude, perceived behavioral
      control), self-regulatory (behavioral processes), and habitual (automaticity)
      constructs. 

PMID- 23873133
TI  - How tendons buffer energy dissipation by muscle.
AB  - To decelerate the body and limbs, muscles lengthen actively to dissipate energy.
      During rapid energy-dissipating events, tendons buffer the work done on muscle by
      storing elastic energy temporarily, then releasing this energy to do work on the
      muscle. This elastic mechanism may reduce the risk of muscle damage by reducing
      peak forces and lengthening rates of active muscle. 

PMID- 23873135
TI  - A further TWEAK to multiple sclerosis pathophysiology.
AB  - Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of
      the TNF super family that controls many cellular activities including
      proliferation, migration, differentiation, apoptosis, and inflammation by binding
      to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell surface
      receptor. Recent studies have indicated that TWEAK-Fn14 axis signaling may
      contribute to chronic autoimmune diseases. TWEAK expression via microglia in
      cortical lesions, presence of TWEAK(+) macrophages in inflamed leptomeninges, and
      absence of TWEAK/Fn14 expression in healthy brain implicates importance of this
      pathway in pathogenesis of multiple sclerosis lesions. TWEAK-Fn14 axis blockade
      has also shown promise in various multiple sclerosis animal models. Stimulation
      of the TWEAK/Fn14 pathway can result in activation of both canonical and
      noncanonical NF-kappaB signaling and could also stimulate mitogen-activated
      protein kinase (MAPK) signaling pathways. Here, we have reviewed evidence of the
      possible role of TWEAK-Fn14 axis in pathophysiology of multiple sclerosis and
      experimental autoimmune encephalomyelitis (EAE) via neuroinflammation, tissue
      remodeling, blood-brain barrier (BBB) disruption, neurodegeneration, and
      astrogliosis. 

PMID- 23873136
TI  - Specific induction of Akt3 in spinal cord motor neurons is neuroprotective in a
      mouse model of familial amyotrophic lateral sclerosis.
AB  - Evidence is accumulating that an imbalance between pathways for degeneration or
      survival in motor neurons may play a central role in mechanisms that lead to
      neurodegeneration in amyotrophic lateral sclerosis (ALS). We and other groups
      have observed that downregulation, or lack of induction, of the PI3K/Akt
      prosurvival pathway may be responsible for defective response of motor neurons to
      injury and their consequent cellular demise. Some of the neuroprotective effects
      mediated by growth factors may involve activation of Akt, but a proof of concept
      of Akt as a target for therapy is lacking. We demonstrate that specific
      expression of constitutively activated Akt3 in motor neurons through the use of
      the promoter of homeobox gene Hb9 prevents neuronal loss induced by SOD1.G93A
      both in vitro (in mixed neuron/astrocyte cocultures) and in vivo (in a mouse
      model of ALS). Inhibition of ASK1 and GSK3beta was involved in the
      neuroprotective effects of activated Akt3, further supporting the hypothesis that
      induction of Akt3 may be a key step in activation of pathways for survival in the
      attempt to counteract motor neuronal degeneration in ALS. 

PMID- 23873137
TI  - Cardiac output assessed by non-invasive monitoring is associated with ECG changes
      in children with critical asthma.
AB  - The primary aim of this study was to determine changes in CI and SI, if any, in
      children hospitalized with status asthmatics during the course of treatment as
      measured by non-invasive EC monitoring. The secondary aim was to determine if
      there is an association between Abnormal CI (defined as <5 or >95 % tile adjusted
      for age) and Abnormal ECG (defined as ST waves changes) Non-invasive cardiac
      output (CO) recordings were obtained daily from admission (Initial) to discharge
      (Final). Changes in CI and SI measurements were compared using paired t tests or
      1-way ANOVA. The association between Abnormal CI on Initial CO recording and
      Abnormal ECG was analyzed by Fischer's exact test. Data are presented as mean +/-
      SEM with mean differences reported with 95 % confidence interval; p < 0.05 was
      considered significant. Thirty-five children with critical asthma were analyzed.
      CI decreased from 6.2 +/- 0.2 to 4.5 +/- 0.1 [-1.6 (-0.04 to -0.37)] L/min/m(2)
      during hospitalization. There was no change in SI. There was a significant
      association between Abnormal Initial CI and Abnormal ECG (p = 0.02). In 11
      children requiring prolonged hospitalization CI significantly decreased from 7.2
      +/- 0.5 to 4.0 +/- 0.2 [-3.2 (-4.0 to -2.3)] L/min/m(2) and SI decreased from
      51.2 +/- 3.8 to 40.3 +/- 2.0 [-11.0 (-17.6 to -4.4)] ml/beat/m(2) There was a
      significant decrease in CI in all children treated for critical asthma. In
      children that required a prolonged course of treatment, there was also a
      significant decrease in SI. Abnormal CI at Initial CO recording was associated
      with ST waves changes on ECG during hospitalization. Future studies are required
      to determine whether non-invasive CO monitoring can predict which patients are at
      risk for developing abnormal ECG.

PMID- 23873138
TI  - An electrochemiluminescence assay for the detection of bio threat agents in
      selected food matrices and in the screening of Clostridium botulinum outbreak
      strains associated with type A botulism.
AB  - BACKGROUND: Specific screening methods for complex food matrices are needed that
      enable unambiguous and sensitive detection of bio threat agents (BTAs) such as
      Bacillus anthracis spores and microbial toxins (e.g. staphylococcal enterotoxin B
      (SEB) and clostridial botulinum neurotoxins (BoNTs)). The present study describes
      an image-based 96-well Meso Scale Discovery (MSD) electrochemiluminescence (ECL)
      assay for simultaneous detection of BTAs in dairy milk products. RESULTS: The
      limit of detection of this ECL assay is 40 pg mL-1 for BoNT/A complex, 10 pg mL-1
      for SEB and 40000 CFU mL-1 for Bacillus anthracis spores in dairy milk products.
      The ECL assay was successfully applied to screen type A Clostridium botulinum
      outbreak strains. CONCLUSION: The results of the study indicate that this ECL
      assay is very sensitive, rapid (<6 h) and multiplex in nature. The ECL assay has
      potential for use as an in vitro screening method for BTAs over other comparable
      immunoassays.

PMID- 23873139
TI  - The role of implantable cardioverter-defibrillators in patients with continuous
      flow left ventricular assist devices.
AB  - BACKGROUND: The prognosis for patients experiencing ventricular arrhythmias (VAs)
      while on continuous flow left ventricular assist device (LVAD) support has not
      been well elucidated. Accordingly, the role of implantable cardioverter
      defibrillators (ICDs) in this patient population remains undefined. METHODS AND
      RESULTS: Records of 106 consecutive patients undergoing implantation of the
      HeartMate II LVAD at a single center were reviewed. For patients surviving >30
      days postimplant (98 patients), the impact of VAs and ICDs on survival was
      analyzed. Mean age was 56.6+/-11.4 years, 82.1% were male, 42.5% had an ischemic
      cardiomyopathy, 87.7% were bridge to transplantation, and median length of
      support was 217 days. Twenty-one (19.8%) patients died, 60 (56.6%) survived to
      transplantation, and 25 patients (23.6%) reached the end of study, had the LVAD
      explanted, or were lost to follow-up. Post-LVAD VAs occurred in 37 patients
      (34.9%) but were not associated with increased mortality (hazard ratio, 0.58
      [0.18-1.90]). Sixty-two (63.3%) patients had an active ICD, and 36 (36.7%)
      patients had no ICD or an inactivated ICD post-LVAD. Patients with an ICD were
      more likely to be INTERMACS (Interagency Registry for Mechanically Assisted
      Circulatory Support) level 3 or 4 at the time of implant (54.8% versus 33.3%;
      P=0.04). An appropriate shock was delivered in 27.3% of patients, but the
      presence of an active ICD was not associated with improved survival (hazard
      ratio, 1.12 [0.37-3.35]). CONCLUSIONS: VAs are common in patients with continuous
      flow LVADs. Although some episodes may be clinically significant, VAs are not
      associated with a worse prognosis, and concomitant ICDs in these patients may not
      reduce mortality.

PMID- 23873140
TI  - Myocardial infarction and atrial fibrillation: importance of atrial ischemia.
AB  - BACKGROUND: Myocardial infarction (MI) is associated with the development of
      atrial fibrillation (AF). We aimed to characterize the atrial abnormalities
      because of MI and determine the role of ischemia to the AF substrate. METHODS AND
      RESULTS: Forty-four sheep were studied. MI was induced by occlusion of the left
      circumflex artery (LCX) or left anterior descending artery (LAD). Excluding 11
      with fatal arrhythmias, equal groups of animals (LCX; LAD; and sham-operated)
      underwent sequential electrophysiology study for 45 minutes to determine atrial
      effective refractory periods, conduction velocity, conduction heterogeneity
      index, and AF inducibility. Postmortem evaluation was performed with 2,3,5
      triphenyl tetrazolium chloride staining. MI resulted in greater left ventricular
      dysfunction (P<0.05), LA pressure (P<0.0003), and reduction in atrial effective
      refractory periods (P<0.0001) compared with control. 2,3,5 triphenyl tetrazolium
      chloride staining demonstrated that the left circumflex artery, and not the LAD,
      group had atrial infarction. The left circumflex artery group demonstrated the
      following compared with the LAD or control groups: greater slowing in atrial
      conduction velocity (P<0.0001 and P<0.001); increased absolute range of
      conduction phase delay (P<0.001 and P<0.001); increased conduction heterogeneity
      index (P<0.0001 and P<0.001); greater AF vulnerability (P<0.05 for both); and
      longer AF duration (P<0.05 for both). LAD group had modest but significant
      slowing in conduction velocity (P<0.01) but no change in conduction heterogeneity
      index or AF duration compared with control. CONCLUSIONS: Left ventricular
      infarction, which is known to result in atrial stretch, hemodynamic change, and
      neurohumoral activation, contributes partially to the atrial abnormalities in MI.
      Atrial ischemia/infarction results in greater atrial electrophysiological changes
      and propensity for AF forming the dominant substrate for AF in MI.

PMID- 23873141
TI  - Transseptal conduction as an important determinant for cardiac resynchronization
      therapy, as revealed by extensive electrical mapping in the dyssynchronous canine
      heart.
AB  - BACKGROUND: Simple conceptual ideas about cardiac resynchronization therapy
      assume that biventricular (BiV) pacing results in collision of right and left
      ventricular (LV) pacing-derived wavefronts. However, this concept is contradicted
      by the minor reduction in QRS duration usually observed. We investigated the
      electric mechanisms of cardiac resynchronization therapy by performing detailed
      electric mapping during extensive pacing protocols in dyssynchronous canine
      hearts. METHODS AND RESULTS: Studies were performed in anesthetized dogs with
      acute left bundle-branch block (LBBB, n=10) and chronic LBBB with tachypacing
      induced heart failure (LBBB+HF, n=6). Activation times (AT) were measured using
      LV endocardial contact and noncontact mapping and epicardial contact mapping. BiV
      pacing reduced QRS duration by 21+/-10% in LBBB but only by 5+/-12% in LBBB+HF
      hearts. Transseptal impulse conduction was significantly slower in LBBB+HF than
      in LBBB hearts (67+/-9 versus 44+/-16 ms, respectively), and in both groups
      significantly slower than transmural LV conduction (~30 ms). In both groups QRS
      duration and vector and the epicardial AT vector amplitude and angle were
      significantly different between LV and BiV pacing, whereas the endocardial AT
      vector was similar. During variation of atrioventricular delay while LV pacing,
      and ventriculo-ventricular delay while BiV pacing, the optimal hemodynamic effect
      was achieved when epicardial AT and QRS vectors were minimal and endocardial AT
      vector indicated LV preexcitation. CONCLUSIONS: Due to slow transseptal
      conduction, the LV electric activation sequence is similar in LV and BiV pacing,
      especially in failing hearts. Optimal hemodynamic cardiac resynchronization
      therapy response coincides with minimal epicardial asynchrony and QRS vector and
      LV preexcitation.

PMID- 23873143
TI  - Locations of high contact force during left atrial mapping in atrial fibrillation
      patients: electrogram amplitude and impedance are poor predictors of electrode
      tissue contact force for ablation of atrial fibrillation.
AB  - BACKGROUND: During radiofrequency ablation, high electrode-tissue contact force
      (CF) is associated with increased risk of steam pop and perforation. The purpose
      of this study, in patients undergoing ablation of paroxysmal atrial fibrillation,
      was to: (1) identify factors producing high CF during left atrial (LA) and
      pulmonary vein mapping; (2) determine the ability of atrial potential amplitude
      and impedance to predict CF; and (3) explore the feasibility of controlling
      radiofrequency power based on CF. METHODS AND RESULTS: A high-density map of
      LA/pulmonary veins (median 328 sites) was obtained in 18 patients undergoing
      atrial fibrillation ablation using a 7.5-Fr irrigated mapping/ablation catheter
      to measure CF. Average CF was displayed on the 3D map. For 5682 mapped sites, CF
      ranged 1-144 g (median 8.2 g). High CF (>=35 g) was observed at only 118/5682
      (2%) sites, clustering in 6 LA regions. The most common high CF site (48/113
      sites in 17/18 patients) was located at the anterior/rightward LA roof, directly
      beneath the ascending aorta (confirmed by merging the CT image and map). Poor
      relationship between CF and either unipolar amplitude, bipolar amplitude, or
      impedance was observed. During ablation, radiofrequency power was modulated based
      on CF. All pulmonary veins were isolated without steam pop, impedance rise, or
      pericardial effusion. CONCLUSIONS: High CF often occurs at anterior/rightward
      roof, where the ascending aorta provides resistance to the LA. Atrial potential
      amplitude and impedance are poor predictors of CF. Controlling radiofrequency
      power based on CF seems to prevent steam pop and impedance rise without loss of
      lesion effectiveness.

PMID- 23873144
TI  - Redox characterization of semiconductors based on electrochemical measurements
      combined with UV-Vis diffuse reflectance spectroscopy.
AB  - Several techniques can be applied to characterize redox properties of wide
      bandgap semiconductors, however some of them are of limited use. In this paper we
      propose a new modification of the old spectroelectrochemical method developed two
      decades ago. A procedure based on measurements of the reflectance changes as a
      function of potential applied to the electrode coated with the studied material
      appears to be a very convenient tool for characterizing redox properties of
      semiconductors, forming either transparent or opaque films at a platinum
      electrode. A discussion on the measured redox parameters of semiconductor films
      concludes with a definition of a new term, the absorption onset potential of the
      material. 

PMID- 23873142
TI  - Electrical homogenization of ventricular scar by application of collagenase: a
      novel strategy for arrhythmia therapy.
AB  - BACKGROUND: Radiofrequency ablation for ventricular tachycardia is an established
      therapy. Use of chemical agents for scar homogenization represents an alternative
      approach. The purpose of this study was to characterize the efficacy of
      collagenase (CLG) application on epicardial ventricular scar homogenization.
      METHODS AND RESULTS: Myocardial infarcts were created in Yorkshire pigs (n=6) by
      intracoronary microsphere injection. After 46.6+/-4.3 days, CLG type 2, type 4,
      and purified CLG were applied in vitro (n=1) to myocardial tissue blocks
      containing normal myocardium, border zone, and dense scar. Histopathologic
      studies were performed to identify the optimal CLG subtype. In vivo high-density
      electroanatomic mapping of the epicardium was also performed, and border zone and
      dense scar surface area and late potentials were quantified before and after CLG
      4 application (n=5). Of the CLG subtypes tested in vitro, CLG-4 provided the best
      scar modification and least damage to normal myocardium. During in vivo testing,
      CLG-4 application decreased border zone area (21.3+/-14.3 to 17.1+/-11.1 mm(2),
      P=0.043) and increased dense scar area (9.1+/-10.3 to 22.0+/-20.6 mm(2),
      P=0.043). The total scar area before and after CLG application was 30.4+/-23.4
      and 39.2+/-29.5 mm(2), respectively (P=0.08). Late potentials were reduced by CLG
      4 application (28.8+/-21.8 to 13.8+/-13.1, P=0.043). During CLG-4 application
      (50.0+/-15.5 minutes), systolic blood pressure and heart rate were not
      significantly changed (68.0+/-7.7 versus 61.8+/-5.3 mmHg, P=0.08; 77.4+/-7.3
      versus 78.8+/-6.0 beats per minute, P=0.50, respectively). CONCLUSIONS:
      Ventricular epicardial scar homogenization by CLG-4 application is feasible and
      effective. This represents the first report on bioenzymatic ablation of
      arrhythmogenic tissue as an alternative strategy for lesion formation.

PMID- 23873145
TI  - Synthesis and structure of the first heterodinuclear bis(borylene) complexes.
AB  - We report a facile synthesis of the first heterodinuclear bis(borylene) complex
      by reaction of an iron bis(borylene) complex with [Pt(PCy3)2], and its fully
      reversible CO uptake and liberation reaction. 

PMID- 23873146
TI  - Consistent high clinical pregnancy rates and low ovarian hyperstimulation
      syndrome rates in high-risk patients after GnRH agonist triggering and modified
      luteal support: a retrospective multicentre study.
AB  - STUDY QUESTION: Are clinical pregnancy rates satisfactory and the incidence of
      OHSS low after GnRH agonist trigger and modified intensive luteal support in
      patients with a high risk of ovarian hyperstimulation syndrome (OHSS)? SUMMARY
      ANSWER: GnRH agonist trigger combined with 1500 IU hCG at the time of oocyte
      retrieval and subsequent estradiol and progesterone replacement in OHSS high-risk
      patients can facilitate fresh embryo transfer with high clinical pregnancy rates
      and a low risk of severe OHSS. WHAT IS KNOWN ALREADY: Conventional luteal support
      packages are inadequate to facilitate a fresh transfer after a GnRH agonist
      trigger. A low dose of hCG (1500 IU) after oocyte aspiration can be used to
      replace the actions of early luteal LH to sustain implantation and the function
      of the early corpus luteum, although the level of risk of severe OHSS with this
      strategy is unclear. STUDY DESIGN, SIZE, DURATION: This international multicentre
      retrospective case study, including 275 women at high risk of OHSS, was
      undertaken during the period January 2011-December 2012. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Women were identified as at high risk of OHSS, based on IVF
      response, ovarian reserve characteristics and previous history of having had
      treatment, in three clinical IVF centres in UK, Belgium and Australia. All three
      centres used a GnRH agonist trigger followed by one bolus of 1500 IU hCG 1h after
      oocyte retrieval. Moreover, the luteal phase was supported with daily vaginal
      progesterone and twice daily estradiol valerate. MAIN RESULTS AND THE ROLE OF
      CHANCE: A total of 275 autologous cycles with fresh transfer were undertaken in a
      cohort of high-risk women as defined by baseline characteristics [median
      (interquartile range)]: age 31.6 (29-35) years, antral follicle count median 25
      (18-34) and anti-Mullerian hormone median 49.1 pmol/l (35.2-69.3). At the end of
      stimulation, the peak estradiol median of 12 000 pmol/l (9400-15 914) and the
      mean oocyte yield of 17.8 +/- 8.4 confirmed a high response. The overall clinical
      pregnancy rate was 41.8% per cycle started, with only two cases of severe OHSS
      reported (0.72%). No significant differences in clinical pregnancy rates between
      centres were identified. LIMITATIONS, REASONS FOR CAUTION: This is a
      retrospective study and future randomized controlled trials will be able to
      compare whether these outcomes can be improved upon by either segmentation of the
      stimulation cycle and embryo transfer or alternative aggressive luteal support
      strategies. WIDER IMPLICATIONS OF THE FINDINGS: In women who are undergoing
      ovarian stimulation and who develop an excessive ovarian response, the use of a
      GnRH agonist trigger combined with modified luteal support can provide the
      opportunity to proceed to fresh embryo transfer with adequate clinical pregnancy
      rates. However, this procedure will not completely eliminate the risk of OHSS and
      for women with an extreme ovarian response or with significant comorbidity, where
      the possibility of severe OHSS is unacceptable, we recommend GnRH agonist trigger
      followed by a freeze-all policy to completely avoid OHSS.

PMID- 23873147
TI  - Paternal age, placental weight and placental to birthweight ratio: a population
      based study of 590,835 pregnancies.
AB  - STUDY QUESTION: Is the age of the father associated with placental weight or the
      ratio of placental weight to birthweight? SUMMARY ANSWER: Placental weight and
      placental to birthweight ratio increased according to increasing paternal age,
      also after adjustment for maternal age. WHAT IS KNOWN ALREADY: High paternal age
      and also high placental to birthweight ratio have been associated with adverse
      pregnancy outcome. STUDY DESIGN, SIZE AND DURATION: We performed a population
      based study and included all singleton births after 22 weeks of gestation in the
      Medical Birth Registry of Norway (n = 590,835) during the years 1999-2009.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: We compared mean placental weight and
      placental to birthweight ratio between paternal age groups. The association of
      paternal age with placental weight was estimated by linear regression analyses,
      and adjustments were made for maternal age, birthweight, parity, offspring sex,
      gestational age at birth, maternal smoking, pre-eclampsia, maternal diabetes
      mellitus and pregnancy after assisted reproductive technology (ART). MAIN RESULTS
      AND THE ROLE OF CHANCE: In pregnancies with fathers aged 20-24 years old, the
      mean placental weight was 656.2 g [standard deviation (SD) 142.8], whereas it was
      677.8 g (SD 160.0) in pregnancies with fathers aged 50 years or older (P <
      0.001). The mean offspring birthweight in pregnancies with fathers aged 20-24
      year old was 3465.0 g (SD 583.8), and it was 3498.9 g (SD 621.8) when the father
      was 50 years or older (P < 0.001). The placental to birthweight ratio in the
      corresponding paternal age groups were 0.191 (SD 0.039) and 0.196 (SD 0.044) (P <
      0.001). In multivariable linear regression analysis the placentas in pregnancies
      fathered by a man of 50 years or older were estimated to weigh 13.99 g [95%
      confidence interval (CI) 10.88-17.10] more than in pregnancies with a 20-24-year
      old father (P < 0.001) after adjustment for maternal age, birthweight, parity,
      offspring sex, gestational age at birth, maternal smoking, pre-eclampsia,
      maternal diabetes mellitus and pregnancy after ART. LIMITATIONS, REASONS FOR
      CAUTION: Paternal age explains only a small proportion of the total variation in
      placental weight. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may increase
      the understanding of the father's role in human pregnancy. STUDY FUNDING/
      COMPETING INTEREST(S): Norwegian Resource Centre for Women's Health, Norway. No
      conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

PMID- 23873148
TI  - A two-step mechanism for epigenetic specification of centromere identity and
      function.
AB  - The basic determinant of chromosome inheritance, the centromere, is specified in
      many eukaryotes by an epigenetic mark. Using gene targeting in human cells and
      fission yeast, chromatin containing the centromere-specific histone H3 variant
      CENP-A is demonstrated to be the epigenetic mark that acts through a two-step
      mechanism to identify, maintain and propagate centromere function indefinitely.
      Initially, centromere position is replicated and maintained by chromatin
      assembled with the centromere-targeting domain (CATD) of CENP-A substituted into
      H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing
      chromatin is shown to require either the amino- or carboxy-terminal tail of CENP
      A for recruitment of inner kinetochore proteins, including stabilizing CENP-B
      binding to human centromeres or direct recruitment of CENP-C, respectively. 

PMID- 23873149
TI  - Uba1 functions in Atg7- and Atg3-independent autophagy.
AB  - Autophagy is a conserved process that delivers components of the cytoplasm to
      lysosomes for degradation. The E1 and E2 enzymes encoded by Atg7 and Atg3 are
      thought to be essential for autophagy involving the ubiquitin-like protein Atg8.
      Here, we describe an Atg7- and Atg3-independent autophagy pathway that
      facilitates programmed reduction of cell size during intestine cell death.
      Although multiple components of the core autophagy pathways, including Atg8, are
      required for autophagy and cells to shrink in the midgut of the intestine, loss
      of either Atg7 or Atg3 function does not influence these cellular processes.
      Rather, Uba1, the E1 enzyme used in ubiquitylation, is required for autophagy and
      reduction of cell size. Our data reveal that distinct autophagy programs are used
      by different cells within an animal, and disclose an unappreciated role for
      ubiquitin activation in autophagy. 

PMID- 23873150
TI  - Vesicles modulate an actin network for asymmetric spindle positioning.
AB  - Actin networks drive many essential cellular processes, including cell migration,
      cytokinesis and tissue morphogenesis. However, how cells organize and regulate
      dynamic actin networks that consist of long, unbranched actin filaments is only
      poorly understood. This study in mouse oocytes reveals that cells can use
      vesicles as adaptable, motorized network nodes to regulate the dynamics and
      density of intracellular actin networks. In particular, Rab11a-positive vesicles
      drive the network dynamics in a myosin-Vb-dependent manner, and modulate the
      network density by sequestering and clustering the network's actin nucleators. We
      also report a simple way by which networks of different densities can be
      generated, namely by adjusting the number and volume of vesicles in the cell.
      This vesicle-based mechanism of actin network modulation is essential for
      asymmetric positioning of the meiotic spindle in mouse oocytes, a vital step in
      the development of a fertilizable egg in mammals. 

PMID- 23873152
TI  - Aging affects AO rat splenic conventional dendritic cell subset composition,
      cytokine synthesis and T-helper polarizing capacity.
AB  - It is well-established that almost all cellular components of innate and adaptive
      immunity undergo age-related remodelling. The findings on age-related changes in
      both human and mouse dendritic cells (DCs) are conflicting, whereas there are no
      data on the influence of aging on rat DCs. In an attempt to fill this gap,
      freshly isolated splenic DCs expressing CD103 (alphaOX-62 integrin), a DC
      specific marker recognized by MRC OX62 monoclonal antibody, from 3- (young) and
      26-month-old (aged) Albino Oxford rats were examined for subset composition,
      expression of activation/differentiation markers (CD80, CD86 and CD40 and MHC II
      molecules) and endocytic capacity using flow cytometric analysis (FCA). In
      addition, splenic OX62+ DCs cultured in the presence or absence of LPS were
      analysed for the activation marker and TNF-alpha, IL-6, IL-12, IL-23, TGF-beta1,
      IL-10 expression using FCA, RT-PCR and ELISA, respectively. Moreover, the
      allostimulatory capacity of OX62+ DCs and IFN-gamma, IL-4 and IL-17 production by
      CD4+ T cells in mixed leukocyte reaction was quantified using FCA and ELISA,
      respectively. It was found that aging: i) shifts the CD4+:CD4- subset ratio in
      the OX62+ DCs population towards the CD4- subset and ii) influences DCs
      maturation (judging by activation marker expression and efficiency of
      endocytosis) by affecting the expression of intrinsic (TNF-alpha and IL-10) and
      extrinsic maturation regulators. Furthermore, in LPS-matured OX62+ DCs from aged
      rats expression of TNF-alpha, IL-12, IL-23 and IL-6 was increased, whereas that
      of IL-10 was diminished compared with the corresponding cells from young rats.
      Moreover, in MLR, OX62+ DCs from aged rats exhibited enhanced Th1/Th17 driving
      force and diminished allostimulatory capacity compared with those from young
      rats.

PMID- 23873153
TI  - Effects of antiretroviral therapy on arterial stiffness in Cameroonian HIV
      infected patients.
AB  - BACKGROUND: HIV infection increases cardiovascular risk and highly active
      antiretroviral therapy may further augment it. We hypothesized that an increase
      in large artery stiffness may be a mechanism of enhanced cardiovascular risk in
      treated HIV-infected (HIV-T) patients. MATERIALS AND METHODS: Pulse wave velocity
      (PWV) and augmentation index (AI) were measured in 108 Cameroonian untreated HIV
      infected (HIV-UT) patients and in 130 HIV-T patients. RESULTS: Brachial and
      aortic systolic blood pressure (BP), diastolic BP, and pulse pressure were higher
      in HIV-T patients than in HIV-UT patients (all, P < 0.01). PWV was comparable in
      HIV-T and HIV-UT patients (7.2 +/- 1.5 vs. 7.46 +/- 2.2 m/s, respectively, P =
      0.3), whereas AI was higher in HIV-T patients than in HIV-UT patients (7.9 +/- 5
      vs. 5.76 +/- 4%, respectively, P = 0.003). AI was associated independently with
      age, brachial systolic BP, brachial diastolic BP, and height in HIV patients (R =
      0.75, P < 0.01). CONCLUSION: This study shows that pulse pressure and AI were
      increased in HIV-T patients, compared with matched HIV-UT patients, suggesting
      that highly active antiretroviral therapy could increase cardiovascular risk.
      However, PWV was not accelerated in HIV-T patients.

PMID- 23873151
TI  - Imaging ROS signaling in cells and animals.
AB  - Reactive oxygen species (ROS) act as essential cellular messengers, redox
      regulators, and, when in excess, oxidative stressors that are widely implicated
      in pathologies of cancer and cardiovascular and neurodegenerative diseases.
      Understanding such complexity of the ROS signaling is critically hinged on the
      ability to visualize and quantify local, compartmental, and global ROS dynamics
      at high selectivity, sensitivity, and spatiotemporal resolution. The past decade
      has witnessed significant progress in ROS imaging at levels of intact cells,
      whole organs or tissues, and even live organisms. In particular, major advances
      include the development of novel synthetic or genetically encoded fluorescent
      protein-based ROS indicators, the use of protein indicator-expressing animal
      models, and the advent of in vivo imaging technology. Innovative ROS imaging has
      led to important discoveries in ROS signaling-for example, mitochondrial
      superoxide flashes as elemental ROS signaling events and hydrogen peroxide
      transients for wound healing. This review aims at providing an update of the
      current status in ROS imaging, while identifying areas of insufficient knowledge
      and highlighting emerging research directions. 

PMID- 23873154
TI  - Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of
      early-stage breast cancer.
AB  - A simple and accurate test to detect early-stage breast cancer has not been
      developed. Previous studies indicate that the level of human endogenous
      retrovirus type K (group HERV-K(HML-2)) transcription may be increased in human
      breast tumors. We hypothesized that HERV-K(HML-2) reactivation can serve as a
      biomarker for early detection of breast cancer. Serum samples were collected from
      women without cancer (controls) and patients with ductal carcinoma in situ (DCIS)
      and invasive breast cancer. ELISA assays were used to detect serum anti-HERV
      K(HML-2) antibody titers. RNA was extracted from sera and analyzed by real-time
      RT-PCR to quantitate the level of HERV-K(HML-2) mRNA. We measured significantly
      higher serum mRNA and serum antibody titers against HERV-K(HML-2) proteins in
      women with DCIS and stage I disease than in women without cancer. At optimized
      cutoffs for the antibody titers, the assay produced an area under the receiver
      operating characteristic curve (AUC) of 0.89 (95% confidence interval 0.77-1.00)
      for DCIS and of 0.95 (95% confidence interval 0.89-1.00) for invasive breast
      cancer. These AUCs are comparable to those observed for mammograms. We also found
      that serum HERV-K(HML-2) mRNA tended to be higher in breast cancer patients with
      a primary tumor who later on developed the metastatic disease than in patients
      who did not develop cancer metastasis. Our results show that HERV-K(HML-2)
      antibodies and mRNA are already elevated in the blood at an early stage of breast
      cancer, and further increase in patients who are at risk of developing a
      metastatic disease. 

PMID- 23873155
TI  - Why the U.S. budget sequester is a disaster for the future of biomedical science.

PMID- 23873156
TI  - Tolerance is different in T and B cells.

PMID- 23873157
TI  - Pillars article: Kinetic differences in unresponsiveness of thymus and bone
      marrow cells. Science. 1971. 171: 813-815.

PMID- 23873158
TI  - Antibody polyreactivity in health and disease: statu variabilis.
AB  - An Ab molecule or a BCR that is able to bind multiple structurally unrelated Ags
      is defined as polyreactive. Polyreactive Abs and BCRs constitute an important
      part of immune repertoires under physiological conditions and may play essential
      roles in immune defense and in the maintenance of immune homeostasis. In this
      review, we integrate and discuss different findings that reveal the indispensable
      role of Ag-binding polyreactivity in the immune system. First, we describe the
      functional and molecular characteristics of polyreactive Abs. The following part
      of the review concentrates on the biological roles attributed to polyreactive Abs
      and to polyreactive BCRs. Finally, we discuss recent studies that link Ig
      polyreactivity with distinct pathological conditions. 

PMID- 23873159
TI  - Expression profiles of Toll-like receptors 1, 2 and 5 in selected organs of
      commercial and indigenous chickens.
AB  - Toll-like receptors (TLRs) are members of the cellular receptors that constitute
      a major component of the evolutionary conserved pattern recognition system (PRR).
      TLRs are expressed in a wide variety of tissues and cell types. In this study we
      compared the expression profiles of the chicken TLR1, TLR2 and TLR5 genes in a
      range of organs (lung, ovary, liver, thymus, duodenum, spleen and large
      intestine) in commercial Hy-Line (HL) and indigenous Green-legged Partridgelike
      (GP) chickens. The level of mRNA was determined with RT-qPCR using the TaqMan
      probes for target and reference (ACTB) genes. We determined that the tissue
      profiles differed with respect to each TLR and they were ranked as follows:
      spleen, lungs, large intestine (TLR1), large intestine, lungs, thymus/ovary
      (TLR2) and lungs, thymus, liver (TLR5). A differential expression between HL and
      GP chickens was determined for TLR1 and TLR5 genes in large intestine and thymus
      of HL (P < 0.05) and GP (P < 0.05) chickens. We conclude that the commercial
      chickens expressed higher levels of TLR1 mRNA in large intestine and TLR5 mRNA in
      thymus than indigenous chickens. 

PMID- 23873160
TI  - The glyceraldehyde-3-phosphate dehydrogenase promoter of the food yeast Candida
      utilis strain NRRL Y-660 is functional in Agrobacterium tumefaciens.
AB  - The glyceraldehyde-3-phosphate dehydrogenase promoter of the food yeast Candida
      utilis strain NRRL Y-660 was cloned to create a novel integrative vector for
      Agrobacterium tumefaciens-mediated transformation. The new binary vector harbors
      beta-glucuronidase activity as reporter and kanamicin/geneticin resistance as
      selection marker. Recombinant clones of A. tumefaciens show kanamycin resistance
      and high beta-glucuronidase activity under the control of the C. utilis promoter.
      This finding can be explained by the presence of a prokaryotic core in the yeast
      promoter, predicted by in silico analysis of the sequence. This is the first
      report about functionality of a yeast promoter in A. tumefaciens. 

PMID- 23873161
TI  - Management of advanced retinoblastoma with intravenous chemotherapy then intra
      arterial chemotherapy as alternative to enucleation.
AB  - PURPOSE: To determine the efficacy of primary intravenous chemotherapy (IVC) plus
      secondary intraarterial chemotherapy (IAC) for patients with advanced
      retinoblastoma. METHODS: Retrospective, nonrandomized interventional case series
      of 14 patients with retinoblastoma managed with primary systemic IVC
      (vincristine, etoposide, and carboplatin for 6 cycles) followed by secondary IAC
      (melphalan for 1-6 cycles). RESULTS: Fourteen patients with advanced
      retinoblastoma classified by the International Classification of Retinoblastoma
      as Group D (n = 6, 43%) or Group E (n = 8, 57%) were treated with IVC as primary
      treatment and subsequent secondary IAC as rescue or consolidation therapy. The
      IAC was given for recurrent retinoblastoma and/or subretinal/vitreous seeds in 13
      eyes (93%) and for persistent viable retinoblastoma in 1 eye (7%). Enucleation
      was the alternative option. The mean interval between IVC completion and IAC
      start was 40 weeks (median, 11 weeks; range, 2-170 weeks) and the mean number of
      IAC cycles was 3 (median, 3; range, 1-6). After primary IVC plus secondary IAC,
      globe salvage was achieved in 8 patients (57%) at mean 2-year follow-up. There
      was no evidence of retinoblastoma metastasis or death and no sign of second
      cancer or life-threatening complication. CONCLUSION: For advanced retinoblastoma
      (Groups D and E) in which enucleation is the alternative option, primary systemic
      IVC followed by secondary focal IAC provides globe salvage in 57% of the eyes and
      with no metastatic event.

PMID- 23873162
TI  - Intravitreal gas injection without vitrectomy for macular detachment associated
      with an optic disk pit.
AB  - PURPOSE: To evaluate the clinical outcomes after gas tamponade without vitrectomy
      for retinal detachment associated with an optic disk pit using optical coherence
      tomography. METHODS: Intravitreal gas injection was performed on 8 consecutive
      patients (mean age, 35.0 years; range, 15-74 years) with unilateral macular
      detachment associated with an optic disk pit. A 0.3-mL injection of 100% sulfur
      hexafluoride 6 gas was carried out without an anterior chamber tap. Patients
      treated with gas injection were instructed to remain facedown for 5 days.
      RESULTS: Complete retinal reattachment after only gas tamponade was achieved in
      four out of eight eyes. The mean number of gas injections was 1.8. The mean best
      corrected visual acuity before and after the treatment with gas tamponade was
      approximately 30/100 and 20/20, respectively. The period required for
      reattachment after final gas treatment was 12 months. There were no incidences of
      recurrence after complete reattachment by gas tamponade in any of the cases
      during the 94-month average follow-up period (range, 64-132 months). CONCLUSION:
      Gas tamponade appears to be an effective alternative method for macular
      detachment associated with an optic disk pit, even though the mechanisms of optic
      disk pit maculopathy are still unknown.

PMID- 23873163
TI  - Analysis of the thickness and vascular layers of the choroid in eyes with
      geographic atrophy using spectral-domain optical coherence tomography.
AB  - PURPOSE: To analyze the total choroidal thickness and thickness of the individual
      vascular layers of the choroid in eyes with geographic atrophy (GA), using
      spectral-domain optical coherence tomography. METHODS: A cross-sectional
      retrospective review identified 17 patients with GA (17 eyes) and 14 age-matched
      healthy subjects (14 eyes), who underwent high-definition raster scanning at New
      England Eye Center, Boston, MA. Patients were diagnosed with GA based on clinical
      examination and investigations. Two independent raters evaluated the thickness
      and vascular layers of the choroid. RESULTS: Mean choroidal thickness was
      significantly lower in eyes with GA when compared with age-matched healthy eyes
      (P < 0.0001). Subfoveal choroidal thickness in eyes with GA was significantly
      less when compared with healthy eyes (158.1 +/- 23.65 MUm versus 267.5 +/- 19.27
      MUm, P = 0.001). Subfoveal large choroidal vessel layer thickness and medium
      choroidal vessel layer/choriocapillaris layer thickness were significantly
      reduced in eyes with GA when compared with healthy eyes (P = 0.001 and P <
      0.0001, respectively). CONCLUSION: The choroid is significantly thinner in eyes
      with GA involving the fovea when compared with healthy eyes. Choroidal thinning
      in GA involves all its vascular layers. Further studies involving prospective
      correlation of choroidal vascular changes to the quantitative progression of GA
      is expected to provide further insight on the choroidal angiopathy associated
      with GA.

PMID- 23873164
TI  - Subvisible retinal laser therapy: titration algorithm and tissue response.
AB  - PURPOSE: Laser therapy for diabetic macular edema and other retinal diseases has
      been used within a wide range of laser settings: from intense burns to
      nondamaging exposures. However, there has been no algorithm for laser dosimetry
      that could determine laser parameters yielding a predictable extent of tissue
      damage. This multimodal imaging and structural correlation study aimed to verify
      and calibrate a computational model-based titration algorithm for predictable
      laser dosimetry ranging from nondamaging to intense coagulative tissue effects.
      METHODS: Endpoint Management, an algorithm based on a computational model of
      retinal photothermal damage, was used to set laser parameters for various levels
      of tissue effect. The algorithm adjusts both power and pulse duration to vary the
      expected level of thermal damage at different percentages of a reference
      titration energy dose. Experimental verification was conducted in Dutch Belted
      rabbits using a PASCAL Streamline 577 laser system. Titration was performed by
      adjusting laser power to produce a barely visible lesion at 20 ms pulse duration,
      which is defined as the nominal (100%) energy level. Tissue effects were then
      determined for energy levels of 170, 120, 100, 75, 50, and 30% of the nominal
      energy at 1 hour and 3, 7, 30, and 60 days after treatment. In vivo imaging
      included fundus autofluorescence, fluorescein angiography, and spectral-domain
      optical coherence tomography. Morphologic changes in tissue were analyzed using
      light microscopy, as well as scanning and transmission electron microscopy.
      RESULTS: One hundred and seventy percent and 120% levels corresponded to moderate
      and light burns, respectively, with damage to retinal pigment epithelium,
      photoreceptors, and at highest settings, to the inner retina. 50% to 75% lesions
      were typically subvisible ophthalmoscopically but detectable with fluorescein
      angiography and optical coherence tomography. Histology in these lesions
      demonstrated some selective damage to retinal pigment epithelium and
      photoreceptors. The 30% to 50% lesions were invisible with in vivo multimodal
      imaging, and damage was limited primarily to retinal pigment epithelium, visible
      best with scanning electron microscopy. Over time, photoreceptors shifted into
      the coagulated zone, reestablishing normal retinal anatomy in lesions <=100%, as
      seen in optical coherence tomography and light microscopy. Transmission electron
      microscopy at 2 months demonstrated restoration of synapses between shifted-in
      photoreceptors and bipolar cells in these lesions. Retinal pigment epithelium
      monolayer restored its continuity after 1 week in all lesions. No damage could be
      seen <30% level. CONCLUSION: A retinal laser dosimetry protocol based on the
      Endpoint Management algorithm provides reproducible changes in retinal morphology
      in animals with various levels of pigmentation. This algorithm opens doors to
      clinical trials of well-defined subvisible and nondestructive regimes of retinal
      therapy, especially important for treatment of macular disorders.

PMID- 23873165
TI  - Diurnal variation in choroidal thickness in relation to sex, axial length, and
      baseline choroidal thickness in healthy Korean subjects.
AB  - PURPOSE: To investigate diurnal variations in choroidal thickness (CT) in
      relation to various factors in healthy Korean subjects using spectral-domain
      optical coherence tomography. METHODS: A prospective study was conducted on 100
      healthy volunteers who each underwent measurements of CT in the same subfoveal
      area using an enhanced depth imaging technique with spectral-domain optical
      coherence tomography at 8 AM, 11 AM, 2 PM, and 5 PM. Possible correlations
      between the diurnal variation of CT and other factors, such as sex, axial length
      (AL), baseline CT (8 AM), blood pressure, and intraocular pressure, were
      evaluated. RESULTS: One hundred volunteers with a mean age of 30.1 years were
      scanned. A significant pattern of diurnal variation was observed, with a mean CT
      of 278.28 +/- 91.78 MUm at 8 AM, 271.57 +/- 89.08 MUm at 11 AM, 266.39 +/- 86.18
      MUm at 2 PM, and 264.92 +/- 87.10 MUm at 5 PM in a right eye. Right eye and left
      eye had a similar trend of diurnal cycle. Based on sex, AL, and baseline CT, the
      pattern of diurnal variation was greater and the amplitude significantly was
      greater in men, AL <= 24 mm and baseline CT >= 300 MUm (men vs. women: P = 0.048,
      AL <= 24 mm vs. AL > 24 mm: P = 0.036, baseline CT >= 300 MUm vs. baseline CT <
      200 MUm: P = 0.002, baseline CT >= 300 MUm vs. 200 MUm <= baseline CT < 300 MUm:
      P = 0.008). There were no significant correlations between the diurnal variation
      of CT and systolic blood pressure, diastolic blood pressure, or intraocular
      pressure. CONCLUSION: In men as well as in those with a shorter AL and thick
      baseline CT, a greater pattern of diurnal variation with significantly greater
      amplitude was observed.

PMID- 23873166
TI  - Use of a Desmarres retractor for upper lid and lash isolation during intravitreal
      injections.

PMID- 23873167
TI  - Reply: To PMID 23099497.

PMID- 23873168
TI  - Multimodal imaging of pigment epithelial detachment: a guide to evaluation.
AB  - PURPOSE: To describe the spectrum of pigment epithelial detachments (PEDs)
      occurring mainly in age-related macular degeneration and central serous
      chorioretinopathy and also in other inflammatory, neoplastic and iatrogenic,
      retinal, and systemic disorders. METHODS: Pigment epithelial detachments are
      divided into drusenoid, serous, vascularized, or mixed categories. RESULTS: The
      clinical presentation, classification, and natural history of PEDs are reviewed
      as illustrated with multimodal imaging combining traditional and novel imaging
      techniques, including fluorescein angiography, indocyanine green angiography,
      fundus autofluorescence, and spectral domain optical coherence tomography. Most
      PEDs occur because of pathophysiologic mechanisms taking place below the retinal
      pigment epithelium that are difficult to identify with conventional imaging
      modalities. Enhanced depth imaging optical coherence tomography and indocyanine
      green angiography allow a better analysis of the subretinal pigment epithelium
      compartment. CONCLUSION: The differentiation between various kinds of PEDs is
      essential because each PED type is a distinct entity that has a specific
      pathogenesis, natural history, prognosis, and optimal treatment strategy.

PMID- 23873169
TI  - Effectiveness and tolerability of electronic cigarette in real-life: a 24-month
      prospective observational study.
AB  - Electronic cigarettes (e-Cigarette) are battery-operated devices designed to
      vaporise nicotine that may aid smokers to quit or reduce their cigarette
      consumption. Research on e-Cigarettes is urgently needed to ensure that the
      decisions of regulators, healthcare providers and consumers are evidence based.
      Here we assessed long-term effectiveness and tolerability of e-Cigarette used in
      a 'naturalistic' setting. This prospective observational study evaluated smoking
      reduction/abstinence in smokers not intending to quit using an e-Cigarette
      ('Categoria'; Arbi Group, Italy). After an intervention phase of 6 months, during
      which e-Cigarette use was provided on a regular basis, cigarettes per day
      (cig/day) and exhaled carbon monoxide (eCO) levels were followed up in an
      observation phase at 18 and 24 months. Efficacy measures included: (a) >=50%
      reduction in the number of cig/day from baseline, defined as self-reported
      reduction in the number of cig/day (>=50%) compared to baseline; (b) >=80%
      reduction in the number of cig/day from baseline, defined as self-reported
      reduction in the number of cig/day (>=80%) compared to baseline; (c) abstinence
      from smoking, defined as complete self-reported abstinence from tobacco smoking
      (together with an eCO concentration of <=10 ppm). Smoking reduction and
      abstinence rates were computed, and adverse events reviewed. Of the 40 subjects,
      17 were lost to follow-up at 24 months. A >50% reduction in the number of cig/day
      at 24 months was shown in 11/40 (27.5%) participants with a median of 24 cig/day
      use at baseline decreasing significantly to 4 cig/day (p = 0.003). Smoking
      abstinence was reported in 5/40 (12.5%) participants while combined >50%
      reduction and smoking abstinence was observed in 16/40 (40%) participants at 24
      months. Five subjects stopped e-Cigarette use (and stayed quit), three relapsed
      back to tobacco smoking and four upgraded to more performing products by 24
      months. Only some mouth irritation, throat irritation, and dry cough were
      reported. Withdrawal symptoms were uncommon. Long-term e-Cigarette use can
      substantially decrease cigarette consumption in smokers not willing to quit and
      is well tolerated. ( http://ClinicalTrials.govnumberNCT01195597 ).

PMID- 23873170
TI  - CHFR silencing or microsatellite instability is associated with increased
      antitumor activity of docetaxel or gemcitabine in colorectal cancer.
AB  - Phenotypic differences among cancers with the same origin may be associated with
      chemotherapy response. CHFR silencing associated with DNA methylation has been
      suggested to be predictive of taxane sensitivity in diverse tumor types. However,
      the use of microsatellite instability (MSI:unstable-MSS:stable) as a predictive
      marker for therapeutic effect has had conflicting results. We examined these
      molecular alterations as predictors of chemotherapy sensitivity in colorectal
      cancer (CRC). Differential sensitivity to docetaxel and gemcitabine was compared
      to potential predictive biomarkers CHFR methylation and MSI status. Cell lines
      that were MSI-H/CHFR-methylated, MSS/CHFR-methylated and MSS/CHFR-unmethylated
      were assessed for in vivo sensitivity of CRC cell line xenografts to docetaxel
      and/or gemcitabine. We observed increased sensitivity in vitro to gemcitabine in
      cell lines with MSI and docetaxel in cell lines with CHFR inactivation via DNA
      methylation. In vivo treatment of human xenografts confirmed differential
      sensitivity, with the MSI-H/CHFR-methylated line RKO having tumor growth
      inhibition to each agent, and at least additive tumor growth inhibition with
      combination therapy. The MSS-CHFR-unmethylated line, CACO2 , was resistant to
      single and combination therapy, while COLO205, the MSS/CHFR-methylated line,
      showed tumor growth inhibition with docetaxel, but not gemcitabine, therapy. CHFR
      methylation in CRC cell lines predicted for sensitivity in vitro and in vivo to
      docetaxel, while MSI-H cell lines were more sensitive to gemcitabine. These data
      suggest that a subset of CRC patients would be selectively sensitive to a novel
      combination of gemcitabine and docetaxel, and are the basis for an ongoing
      clinical trial of this combination in a biomarker-selected patient population. 

PMID- 23873171
TI  - Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV
      vaccination in a randomized clinical trial in Costa Rica.
AB  - BACKGROUND: Human papillomavirus (HPV) infection, particularly with type 16,
      causes a growing fraction of oropharyngeal cancers, whose incidence is
      increasing, mainly in developed countries. In a double-blind controlled trial
      conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine
      against cervical infections and lesions, we estimated VE against prevalent oral
      HPV infections 4 years after vaccination. METHODS AND FINDINGS: A total of 7,466
      women 18-25 years old were randomized (1?1) to receive the HPV16/18 vaccine or
      hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840
      participants provided oral specimens (91.9% of eligible women) to evaluate VE
      against oral infections. Our primary analysis evaluated prevalent oral HPV
      infection among all vaccinated women with oral and cervical HPV results.
      Corresponding VE against prevalent cervical HPV16/18 infection was calculated for
      comparison. Oral prevalence of identifiable mucosal HPV was relatively low
      (1.7%). Approximately four years after vaccination, there were 15 prevalent
      HPV16/18 infections in the control group and one in the vaccine group, for an
      estimated VE of 93.3% (95% CI = 63% to 100%). Corresponding efficacy against
      prevalent cervical HPV16/18 infection for the same cohort at the same visit was
      72.0% (95% CI = 63% to 79%) (p versus oral VE = 0.04). There was no statistically
      significant protection against other oral HPV infections, though power was
      limited for these analyses. CONCLUSIONS: HPV prevalence four years after
      vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women
      in the vaccine arm compared to the control arm, suggesting that the vaccine
      affords strong protection against oral HPV16/18 infection, with potentially
      important implications for prevention of increasingly common HPV-associated
      oropharyngeal cancer. ClinicalTrials.gov, Registry number NCT00128661.

PMID- 23873172
TI  - Comment on Wei et al.: Comparison of artificial total disc replacement versus
      fusion for lumbar degenerative disc disease: a meta-analysis of randomized
      controlled trials.

PMID- 23873173
TI  - Internal fixation of distal tibiofibular syndesmotic injuries: a systematic
      review with meta-analysis.
AB  - No consensus had been reached about the optimal method for syndesmotic fixation.
      The present study analysed syndesmotic fixation based on the highest level of
      clinical evidence in order to obtain more reliable results. Medline, Embase and
      Cochrane database were searched through the OVID retrieval engine. Manual
      searching was undertaken afterward to identify additional studies. Only
      randomized controlled trials (RCT) and prospective comparative studies were
      selected for final inclusion. Study screening and data extraction were completed
      independently by two reviewers. All study characteristics were summarized into a
      table. The extracted data were used for data analysis. Twelve studies were
      finally included: six of them were RCTs, two were quasi-randomized studies and
      four were prospective comparative studies. Four comparisons with traditional
      metallic screw were identified in terms of bioabsorbable screws, tricortical
      fixation method, suture-button device as well as non-fixation choice in low
      syndesmotic injuries. Both absorbable screws and the tricortical fixation method
      showed almost no better results than traditional quadricortical metallic screw (p
      > 0.05). Additionally, existing studies could not illustrate their efficiency of
      reducing hardware removal rate. The suture button technique had significantly
      better functional score (p = 0.003), ankle motion (p = 0.02), time to full
      weightbearing (p < 0.0001) and much less complications (p = 0.0008) based on
      short and intermediate term follow-up data. Transfixation in low syndesmotic
      injuries showed poorer results than the non fixed group in all outcome
      measurements, but didn't reach a significant level (p > 0.05). The present
      evidence still couldn't find superior performance of the bioabsorbable screw and
      tricortical fixation method. Their true effects in decreasing second operation
      rate need further specific studies. Better results of the suture-button made it a
      promising technique, but it still needs long-term testing and cost-efficiency
      studies. The patients with low syndemotic injuries should be well assessed before
      fixation determination and the indication of screw placement in such conditions
      needs to be further defined.

PMID- 23873174
TI  - Proximal opening wedge metatarsal osteotomy for correction of moderate to severe
      hallux valgus deformity using a locking plate.
AB  - PURPOSE: Hallux valgus is a complex deformity of the first metatarsophalangeal
      joint, with varus angulation of the first metatarsal, valgus deviation of the
      great toe and lateral displacement of the sesamoids and the extensor tendons. The
      aim of the surgery is to achieve correction of the varus deviation of the 1st
      metatarsal which is considered by some as the primary intrinsic predisposing
      factor to hallux valgus deformity. METHODS: We retrospectively reviewed 85
      patients (107 feet) who underwent an opening wedge osteotomy of the 1st
      metatarsal for correction of moderate to severe hallux valgus and metatarsus
      primus varus. A medially applied anatomic pre-contoured locking plate was used
      for fixation of the osteotomy. RESULTS: The mean IMA was decreased from 15.8
      (range 12-22) degrees to 7.8 (range 0-12) degrees. The mean pre-operative HVA was
      39 (range 21-52) degrees and the mean postoperative HVA was 11.8 (6-19) degrees.
      The pre-operative AOFAS score was 52 (SD 3.1) and the postoperative score was 85
      (SD 5.2). CONCLUSION: The proximal opening wedge metatarsal osteotomy is a safe,
      effective and reproducible technique for correction of moderate to severe hallux
      valgus deformity. The use of a locking plate provides enough control at the
      fragments, enhancing healing of osteotomy and maintenance of the correction even
      with a violated proximal lateral cortex.

PMID- 23873175
TI  - Metal-enhanced fluorescence based excitation volumetric effect of plasmon
      enhanced singlet oxygen and super oxide generation.
AB  - In this contribution we show that the Metal-Enhanced Fluorescence (MEF)
      Excitation Volumetric Effect (EVE), has a profound effect on the formation of
      Reactive Oxygen Species (ROS), such as singlet oxygen ((1)O2) and superoxide
      anion radical (O2(-)*), when sensitizers are placed in close proximity to plasmon
      supporting nanoparticulate substrates. In particular, when the singlet oxygen
      sensitizer rose bengal is placed on a SiFs surface, i.e. on a silver island film,
      the (1)O2 response to power is non-linear, and at 100 mW excitation power (535
      nm) it is about 5 times higher, as compared to glass control samples, measured
      with the commercially available (1)O2 probe Sensor GreenTM. We also report a
      similar power dependence of superoxide generation for acridine on SiFs surfaces,
      but using the dihydroethidium O2(-)* probe (DHE). Our findings are consistent
      with our previously postulated Metal-Enhanced Fluorescence (MEF) and EVE models.

PMID- 23873176
TI  - [Subclinical hyperthyroidism].
AB  - Subclinical hyperthyroidism is defined as abnormal low TSH level with thyroid
      hormones within their reference range. This laboratory condition may be
      symptomatic in a relevant number of patients leading to tachycardia, sweating,
      nervousness, anxiety and insomnia. The risk for cardiovascular disease is
      increased with more frequent atrial fibrillation and increased left ventricular
      mass including diastolic dysfunction. Cardiovascular mortality and overall
      mortality surmounts the average of the normal population. Longterm TSH
      suppression leads to decreased bone mineral density and an increased fracture
      rate in the hip and in the spine. After evaluation of underlying causes, therapy
      should be considered, especially if TSH levels are below 0.1 mIU/l.

PMID- 23873177
TI  - Human mammary tumor virus (HMTV) in endometrial carcinoma.
AB  - OBJECTIVE: Human mammary tumor virus (HMTV) is 90% to 98% homologous to mouse
      mammary tumor virus, the etiological agent of mammary tumors in mice. Human
      mammary tumor virus sequences were found in 40% of the breast cancers studied in
      both American and Australian women. In addition, 10% of endometrial carcinomas
      studied in Australian women also contained HMTV sequences. We have explored the
      possibility that endometrial cancer of American women may also contain HMTV.
      METHODS/MATERIALS: Nested polymerase chain reactions, radioactive internal
      probing, and sequencing were used to establish the presence of unique nucleotide
      sequences of HMTV in human genomic DNA. The genomic DNAs were tested to guarantee
      that they were free of murine DNA. Immunohistochemistry with a monoclonal
      antibody specific for HMTV envelope protein demonstrated that HMTV sequences were
      translated. RESULTS: Thirteen (23.2%) of 56 of the endometrial cancers studied
      contained HMTV sequences and proteins. Human mammary tumor virus sequences and
      protein were not detected in the 33 normal endometria studied. CONCLUSION: Human
      mammary tumor virus, an agent with high homology to mouse mammary tumor virus,
      was found in 23.2% of the endometrial cancers studied, thus opening the
      possibility of a pathogenic role.

PMID- 23873178
TI  - Vitamin D receptor BsmI polymorphism and ovarian cancer risk: a meta-analysis.
AB  - OBJECTIVE: Vitamin D receptor (VDR) FokI polymorphism has been reported to
      influence ovarian cancer (OC) susceptibility, but the association between VDR
      BsmI polymorphism and OC risk remains controversial. To clarify the relationship
      between them, we performed a meta-analysis. METHODS: A comprehensive literature
      search was conducted to examine all the eligible studies of VDR BsmI polymorphism
      and OC risk. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to
      assess the strength of this association. RESULTS: Seven separate comparisons
      consisting of 1977 OC cases and 2832 healthy controls were included in our meta
      analysis. The pooled analyses showed no significant association between VDR BsmI
      G/A polymorphism and OC in all of the comparisons (AA vs GG: OR, 1.01; P = 0.919;
      AG vs GG: OR, 1.12; P = 0.087; AG + AA vs GG: OR, 1.10; P = 0.146; AA vs AG + GG:
      OR, 0.96; P = 0.629). However, subgroup analysis showed a significant
      contribution of the dominant inheritance model to OC development in the European
      group: AG + AA vs GG (OR, 1.43; P = 0.029); AG vs GG (OR, 1.46; P = 0.031).
      CONCLUSIONS: Vitamin D receptor BsmI G/A gene variant might be a moderate risk
      factor of OC development in the European population instead of North America or
      Asian population.

PMID- 23873179
TI  - Polymorphisms in the genes related to angiogenesis are associated with uterine
      cervical cancer.
AB  - INTRODUCTION: The expression of plasminogen activator inhibitor type 1 (PAI-1),
      vascular endothelial growth factor (VEGF), and transforming growth factor beta1
      (TGF-beta1) participates in the angiogenesis of several cancer types. The goal of
      this study was to investigate polymorphisms in genes related to angiogenesis (PAI
      1-675 4G/5G, VEGF C936T, and TGF-beta1 G-800A) to evaluate the risk for
      developing uterine cervical cancer (UCC). METHODS: In a case-control study, 100
      healthy subjects and 100 patients with UCC from Mexico were included. We
      determined the genetic profile of the polymorphic markers, which were evaluated
      by polymerase chain reaction using a sequence-specific primer. RESULTS: There was
      no statistical difference in the allele distribution from the intergroup
      comparisons of PAI-1 675 4G/5G and VEGF C936T data; however, a significant
      difference was observed within TGF-beta1 G-800A. The linkage disequilibrium
      analysis revealed that PAI-1 -675 4G and TGF-beta1 -800A pair-haplotype was in
      strong linkage disequilibrium with a significantly increased risk (odds ratio,
      3.44; 95% confidence interval, 1.66-7.25) to UCC. CONCLUSIONS: The polymorphisms
      in the genes related to angiogenesis -675 4G/5G PAI-1 and G-800A TGF-beta1,
      segregated solely or combined, might contribute to the increased susceptibility
      to UCC in a Mexican population.

PMID- 23873180
TI  - Comments on "exposure assessment of mobile phone base station radiation in an
      outdoor environment using sequential surrogate modeling" by Aerts et al.

PMID- 23873181
TI  - Photocatalytic water splitting for hydrogen generation on cubic, orthorhombic,
      and tetragonal KNbO3 microcubes.
AB  - Potassium niobate (KNbO3) microcubes with orthorhombic and tetragonal phases were
      hydrothermally prepared and characterized by powder X-ray diffraction, nitrogen
      adsorption-desorption, micro-Raman spectroscopy, Fourier transform infrared
      spectroscopy, diffuse reflectance UV-visible spectroscopy, X-ray photoelectron
      spectroscopy, scanning electron microscopy, and high-resolution transmission
      electron microscopy. The photoreactivity of the as-prepared KNbO3 samples was
      evaluated regarding the hydrogen evolution from aqueous methanol under UV, and
      the results were compared with that of cubic KNbO3 microcubes. The photocatalytic
      reactivity was shown to be phase-dependent, following the order cubic >
      orthorhombic > tetragonal. Insight into the phase-dependent photocatalytic
      properties was gained by first-principles density functional calculations. The
      best photocatalytic performance of cubic KNbO3 is ascribed to it having the
      highest symmetry in the bulk structure and associated unique electronic
      structure. Further, the surface electronic structure plays a key role leading to
      the discrepancy in photoreactivity between orthorhombic and tetragonal KNbO3. The
      results from this study are potentially applicable to a range of perovskite-type
      mixed metal oxides useful in water splitting as well as other areas of
      heterogeneous photocatalysis. 

PMID- 23873182
TI  - A simple method for deriving functional MSCs and applied for osteogenesis in 3D
      scaffolds.
AB  - We describe a simple method for bone engineering using biodegradable scaffolds
      with mesenchymal stem cells derived from human induced-pluripotent stem cells
      (hiPS-MSCs). The hiPS-MSCs expressed mesenchymal markers (CD90, CD73, and CD105),
      possessed multipotency characterized by tri-lineages differentiation: osteogenic,
      adipogenic, and chondrogenic, and lost pluripotency - as seen with the loss of
      markers OCT3/4 and TRA-1-81 - and tumorigenicity. However, these iPS-MSCs are
      still positive for marker NANOG. We further explored the osteogenic potential of
      the hiPS-MSCs in synthetic polymer polycaprolactone (PCL) scaffolds or PCL
      scaffolds functionalized with natural polymer hyaluronan and ceramic TCP (PHT)
      both in vitro and in vivo. Our results showed that these iPS-MSCs are
      functionally compatible with the two 3D scaffolds tested and formed typically
      calcified structure in the scaffolds. Overall, our results suggest the iPS-MSCs
      derived by this simple method retain fully osteogenic function and provide a new
      solution towards personalized orthopedic therapy in the future. 

PMID- 23873183
TI  - [Visual working memory].
AB  - Functional magnetic resonance imaging (fMRI) using the blood oxygenation level
      dependent (BOLD) response depicts the neuroanatomical correlates of cognitive
      processes and contributes to the understanding of memory functions. Working
      memory utilizes different neuroanatomical areas for temporarily storing and
      manipulating information content. Visual working memory is mainly considered to
      be an interaction of the prefrontal cortex which contributes to attention
      functions, temporal regions which store different object categories and posterior
      parietal and occipital regions which are sensitive to object number and
      complexity and possibly also store parts of objects. Expertise leads to the
      creation of long-term entries that support visual working memory entries. Well
      known objects are represented with less neural effort in regions of the visual
      working memory network than unknown objects. 

PMID- 23873184
TI  - [Radiological evaluation of incidental pulmonary nodules].
AB  - Since the widespread use of computed tomography (CT), the detection of pulmonary
      nodules has considerably increased and has become part of the daily clinical
      routine. In the evaluation of pulmonary nodules, malignant nodules have to be
      differentiated from benign pulmonary nodules with a high level of confidence. The
      diagnostic approach for pulmonary nodules depends on the pretest probability for
      malignancy. For indeterminate pulmonary nodules <8 mm, non-contrast CT
      observational follow-up is recommended and depending on the size and pretest
      probability for malignancy, follow-up CT intervals range from 3 to 12 months. For
      indeterminate pulmonary nodules >8 mm, management is based on patient surgical
      risk and pretest probability for malignancy. Either CT follow-up alone, 18
      fluorodeoxyglucose-positron emission tomography (FDG-PET) or non-surgical biopsy
      for tissue diagnosis are utilized to evaluate the lesions. For pulmonary nodules
      with a high pretest probability for malignancy, surgical resection is recommended
      unless specifically contraindicated. 

PMID- 23873186
TI  - Homoeologous relationship of rye chromosome arms as detected with wheat PLUG
      markers.
AB  - Based on the similarity in gene structure between rice and wheat, the polymerase
      chain reaction (PCR)-based landmark unique gene (PLUG) system enabled us to
      design primer sets that amplify wheat genic sequences including introns. From the
      previously reported wheat PLUG markers, we chose 144 markers that are distributed
      on different chromosomes and in known chromosomal regions (bins) to obtain rye
      specific PCR-based markers. We conducted PCR with the 144 primer sets and the
      template of the Imperial rye genomic DNA and found that 131 (91.0%) primer sets
      successfully amplified PCR products. Of the 131 PLUG markers, 110 (76.4%) markers
      showed rye-specific PCR amplification with or without restriction enzyme
      digestion. We assigned 79 of the 110 markers to seven rye chromosomes (1R to 7R)
      using seven wheat-rye (cv. Imperial) chromosome addition and substitution lines:
      12 to 1R, 8 to 2R, 11 to 3R, 8 to 4R, 16 to 5R, 12 to 6R, and 12 to 7R.
      Furthermore, we located their positions on the short or long (L) chromosome arm,
      using 13 Imperial rye telosomic lines of common wheat (except for 3RL). Referring
      to the chromosome bin locations of the 79 PLUG markers in wheat, we deduced the
      syntenic relationships between rye and wheat chromosomes. We also discussed
      chromosomal rearrangements in the rye genome with reference to the cytologically
      visible chromosomal gaps.

PMID- 23873187
TI  - T cells in the human metastatic melanoma microenvironment express site-specific
      homing receptors and retention integrins.
AB  - T-cell infiltration into the metastatic melanoma microenvironment (MME)
      correlates with improved patient survival. However, diffuse infiltration into
      tumor occurs in only 8% of melanoma metastases. Little is known about mechanisms
      governing T-cell infiltration into human melanoma metastases or about how those
      mechanisms may be altered therapeutically. We hypothesized that T cells in the
      MME would be enriched for chemokine receptors CCR4, CCR5, CXCR3 and homing
      receptors relevant to the tissue site. Viably cryopreserved single cell
      suspensions from nineteen melanoma metastases representing three metastatic sites
      (tumor-infiltrated lymph node, skin and small bowel) were evaluated by
      multiparameter flow cytometry and compared to benign lymph nodes and peripheral
      blood mononuclear cells from patients with Stage IIB-IV melanoma. T cells in the
      melanoma metastases contained large effector memory populations, high proportions
      of activated, moderately differentiated cells and few regulatory T cells. Site
      specific homing was suggested in bowel, with high expression of CCR9. We neither
      encounter the anticipated enrichment of integrin alpha4beta7 in bowel, cutaneous
      leukocyte antigen (CLA) in skin, nor integrin alpha4beta1 or receptor CXCR3 in
      metastatic sites. Retention integrins alphaEbeta7, alpha1beta1 and alpha2beta1
      were significantly elevated in metastases. These data suggest limited tissue site
      specific homing to human melanoma metastases, but a significant role for
      retention integrins in maintaining intratumoral T cells. Our findings also raise
      the possibility that T-cell homing, infiltration, and retention in melanoma
      metastases may be increased by increasing expression of ligands for CLA,
      alpha4beta1 and CXCR3 on intratumoral endothelium. 

PMID- 23873189
TI  - Manpower planning in public health: what do we need to do?

PMID- 23873188
TI  - Localization of rRNA genes in the nuclear space of Calliphora erythrocephala Mg.
      nurse cells during polytenization.
AB  - Multicolor 3D fluorescence in situ hybridization was used to study arrangement of
      rRNA genes in Calliphora erythrocephala nurse cell nuclei with different levels
      of polyteny. It has been shown that the rRNA genes are exclusively localized to
      chromosome 6, suggesting that chromosome 6 is the only C. erythrocephala
      chromosome responsible for nucleolar formation. We have also described changes in
      localization of ribosomal genes within the chromosome territory during
      polytenization, namely, that rDNA signals are detected in the peripheral region
      of chromosome territory starting from the stage of polytene chromosomes. In
      addition, it has emerged that large nucleolus associated with chromosome 6 starts
      to develop in the central nuclear region in the C. erythrocephala nurse cell
      nuclei at the stage of a primary reticular structure. The central position and
      nucleolar structure are retained at the stages when chromosome 6 occupies the
      central position, that is, at the stages of polytene and bloblike chromosomes.
      When the nucleus restores a reticular structure but at a higher polyteny level,
      the displacement of chromosome 6 to the nuclear periphery is accompanied by
      disruption of the large nucleolus into micronucleoli. The micronucleoli are
      distributed in the nuclear space retaining their association with the nucleolar
      organizing regions of chromosome 6. Thus, our data suggest that the large-scale
      alterations in the organization of chromosome 6 and the nucleolus during
      polytenization are the correlated processes directly dependent on the rRNA gene
      activity. The earlier described dynamics of nucleolar-organizing chromosome
      territory and nucleolus in the nuclear space is likely to be associated with the
      change in the total expression activity of the nucleus, which complies with the
      hypothesis on the correlation between spatial nuclear organization and expression
      regulation of genetic material.

PMID- 23873190
TI  - Strengthening of primary health care: key to deliver inclusive health care.
AB  - Inequity and poverty are the root causes of ill health. Access to quality health
      services on an affordable and equitable basis in many parts of the country
      remains an unfulfilled aspiration. Disparity in health care is interpreted as
      compromise in 'Right to Life.' It is imperative to define 'essential health
      care,' which should be made available to all citizens to facilitate inclusivity
      in health care. The suggested methods for this include optimal utilization of
      public resources and increasing public spending on health care. Capacity building
      through training, especially training of paramedical personnel, is proposed as an
      essential ingredient, to reduce cost, especially in tertiary care. Another aspect
      which is considered very important is improvement in delivery system of health
      care. Increasing the role of 'family physician' in health care delivery system
      will improve preventive care and reduce cost of tertiary care. These observations
      underlie the relevance and role of Primary health care as a key to deliver
      inclusive health care. The advantages of a primary health care model for health
      service delivery are greater access to needed services; better quality of care; a
      greater focus on prevention; early management of health problems; and cumulative
      improvements in health and lower morbidity as a result of primary health care
      delivery. 

PMID- 23873191
TI  - Surrogacy and women's right to health in India: issues and perspective.
AB  - The human body is a wonderful machine. The future of child birth in the form of
      test tube babies, surrogate motherhood through new reproductive and cloning
      technology will introduce undreamt of possibilities in the sexual arena.
      Surrogacy is a method of assisted reproduction whereby a woman agrees to become
      pregnant for the purpose of gestating and giving birth to a child for others to
      raise. In some jurisdictions the possibility of surrogacy has been allowed and
      the intended parents may be recognized as the legal parents from birth.
      Commercial surrogacy, or "Womb for rent", is a growing business in India. In our
      rapidly globalizing world, the growth of reproductive tourism is a fairly recent
      phenomenon. Surrogacy business is exploiting poor women in country like India
      already having with an alarmingly high maternal death rate. This paper talks
      about paternity issues and women's right to health in context of surrogacy.
      Government must seriously consider enacting a law to regulate surrogacy in India
      in order to protect and guide couples going in for such an option. Without a
      foolproof legal framework, patients will invariably be misled and the surrogates
      exploited. 

PMID- 23873193
TI  - Retraction.

PMID- 23873192
TI  - Cost of dementia care in India: delusion or reality?
AB  - CONTEXT: In 2010, nearly 37 lakh Indians have been estimated to be suffering from
      dementia. Estimated costs of care in published literature do not reflect the
      actual expenses of individual households. Hence, a household budget approach was
      undertaken to arrive at the costs of dementia care in India. MATERIALS AND
      METHODS: We identified and listed the different components of care, classified
      the applicability of care for the different components with respect to mild,
      moderate, and severe cases. This framework was utilized to assign costs of care
      and arrive at the household costs of care for a Person with Dementia (PwD) in
      both urban and rural areas. RESULTS: The total expense was similar to that
      reported by individual households. The annual household cost of caring for a
      person with dementia in India, depending on the severity of the disease, ranged
      between INR 45,600 to INR 2,02,450 in urban areas and INR 20,300 to INR 66,025 in
      rural areas. Costs increased with increasing severity of the disease process. The
      costs of informal care contributed to nearly half of the total costs either in
      rural or urban area. With increasing severity, proportion of medical costs
      decreased while social cost increased. Medical costs in rural areas were nearly
      one-third of the total costs as against less than one-fifth in urban areas.
      CONCLUSION: The household budget model realistically estimated the household
      costs of care. It is hoped that the comprehensive and generic framework would
      prompt health professionals, researchers, and policy makers in India to catalyze
      geriatric health services, particularly for care for PwD.

PMID- 23873194
TI  - Causes of death in rural adult population of North India (2002-2007), using
      verbal autopsy tool.
AB  - BACKGROUND: With the on-going epidemiological transition, information on the
      pattern of mortality is important for health planning. Verbal autopsy (VA) is an
      established tool to ascertain the cause of death in areas where routine
      registration systems are incomplete or inaccurate. We estimated cause-specific
      mortality rates in rural adult population of 28 villages of Ballabgarh in North
      India using VA. MATERIALS AND METHODS: During 2002-2007, trained multi-purpose
      health workers conducted 2294 VA interviews and underlying cause of death was
      coded by physicians. Proportional mortality (%) was calculated by dividing the
      number of deaths attributed to a specific cause by the total number of deaths for
      which a VA was carried out. FINDINGS: 61% of deaths occurred among males and 59%
      occurred among those aged >=60 years. The leading causes of death were diseases
      of the respiratory system (18.7%) and the circulatory system (18.1%). Infectious
      causes and injuries and other external causes, each accounted for around 15% of
      total deaths followed by neoplasms (6.8%) and diseases of the digestive system
      (4%). Among those 45 years of age or more than half of deaths were attributed to
      non-communicable diseases (NCDs) alone. Accidents and injuries were responsible
      for one-fourth of deaths in 15-30 years age group. CONCLUSION: NCDs and injuries
      are emerging as major causes of death in this region thereby posing newer
      challenges to public health system.

PMID- 23873195
TI  - Sexual behavior among unmarried business process outsourcing employees in
      Chennai: gender differences and correlates associated with it.
AB  - BACKGROUND: Premarital sex is often associated with high risk sexual behavior
      such as early age of initiation, multiple partners and inconsistent condom use.
      Evidence shows that such sexual behavior pre-disposes to sexually transmitted
      diseases including HIV. OBJECTIVES: This paper tried to investigate the
      correlates of premarital sexual behavior among male and female business process
      outsourcing (BPO) employees to highlight the gender differences that exist in
      relation to it. MATERIALS AND METHODS: Data were collected from 526 unmarried BPO
      employees during behavioral surveillance survey in Chennai, in the year 2009.
      RESULTS: The results showed that about one-third of respondents (males - 39.6%,
      females - 26.1%) had experienced premarital sex. Men reported having had their
      first sexual intercourse at 12 years and women at 16 years of age. While the
      prevalence of premarital sex was found to be high, the percentage using a condom
      during last sex was also high, especially, among the female employees (82.4%).
      Logistic regression showed that monthly individual income, work in shifts,
      migration, peer influence and friends with previous sexual experience were
      significant predictors of premarital sex among the male BPO employees. Visit to
      night clubs was significantly associated with a higher prevalence of premarital
      sex among the female employees. CONCLUSIONS: The study concludes that there is a
      significant gender dimension in the premarital sexual behavior among the BPO
      employees and that even as the sexual behavior of the young people is
      transitioning; their ability to negotiate safe sex behavior is also increasing.
      It is recommended to enhance efforts to advocate safe sex behavior among young
      adults employed in the BPO industry.

PMID- 23873196
TI  - Awareness of the association between periodontal disease and pre-term births
      among general dentists, general medical practitioners and gynecologists.
AB  - In the recent decades, periodontal disease has been identified as a risk factor
      for pre-term deliveries. Hence, it is important to evaluate the awareness of
      health-care providers of the association between periodontal diseases and pre
      term birth. A self-administered questionnaire was distributed to random samples
      representing general medical practitioners (GMPs), general dental practitioners
      (GDPs) and Gynecologists for this study. A knowledge score was calculated for
      correct answers to 11 survey questions related to oral health effects during
      pregnancy and compared among the three groups. In this study, 133 physicians, 135
      dentists and 100 Gynecologists completed the questionnaire. More GDPs (67.4%)
      than GMPs (56.4%) and Gynecologists (63%) reported there was an association
      between periodontal disease and pre-term low birth weight. Efforts to increase
      this awareness may prove valuable in improving preventive care during pregnancy. 

PMID- 23873197
TI  - Perception of personal risk of acquiring human immunodeficiency viral
      infection/acquired immune deficiency syndrome among people attending outpatient
      clinics in a teaching hospital of Nigeria.
AB  - The Human Immunodeficiency Virus (HIV) pandemic is on the increase with the
      highest burden in sub-Saharan Africa. This descriptive cross-sectional study was
      carried out in 2008 to assess the knowledge, self-perception of risk of
      contracting HIV infection and risky sexual practices among patients attending
      some out-patient clinics at the University Teaching Hospital, Ado-Ekiti, Ekiti
      State, Nigeria. The knowledge on the modes of transmission and methods of
      prevention of HIV was high. Although, 53.0% of the study participants perceived
      themselves not to be at risk of contracting HIV infection, 80.6% were engaged in
      risky sexual practices within a year preceding the study. Significantly more
      participants with multiple sexual partners, past and present history of Sexually
      Transmitted Infections (STI) perceived themselves not to be at risk (P= 0.001,
      0.008 and 0.001 respectively). Effective strategies must therefore be developed,
      to enhance risk-perception since poor risk-perception is known to mitigate
      behavioral change. 

PMID- 23873198
TI  - Predictors of mortality among the neonates transported to referral centre in
      Delhi, India.
AB  - A descriptive study was conducted with an objective to determine the predictors
      of mortality among referred neonates and to ascertain their transport
      characteristics. A total of 300 consecutive neonates who were transferred to the
      centre were enrolled in the study. Following information were recorded: maternal
      details, birth details, interventions before transportation, details of
      transportation and neonatal condition at arrival. Detailed clinical assessment
      and management was done as per standard neonatal protocols. Birth weight <1 kg
      (OR 0.04; 95% CI: 0.006-0.295, P<0.01) and transportation time >1 hour (OR 5.58;
      95% CI: 1.41-22.01, P=0.01) were found to be significant predictors for mortality
      among the transported neonate. Transport characteristics reflect road transport
      with limited utility of ambulances and lack of trained health personal. Hence to
      conclude, extreme low birth weight and prolonged transportation time were found
      to be significant predictors of neonatal mortality among the transported neonate.

PMID- 23873199
TI  - Periodontal status among tobacco users in Karnataka, India.
AB  - A cross-sectional study was designed to assess the prevalence of periodontal
      diseases among tobacco and non-tobacco users. A total of 2,156 dentate subjects
      were selected in the age group of 35-44 years through multi-stage sampling
      method. A total of 350 and 175 subjects were selected from household survey from
      each district in rural and urban areas. Subjects were interviewed for the tobacco
      usage status, followed by clinical assessment of periodontal status. Prevalence
      of calculus, periodontal pockets of 4-5 mm depth and loss of attachment of 0-3 mm
      and 4-5 mm was significantly more frequent among current tobacco users. The
      subject with smoking and chewing tobacco has an odds ratio (OR) 1.6 (95%
      confidence intervals [CI] 1.14-2.31) and OR 1.7 (95% CI 1.38-2.28) respectively.
      The findings contribute to the evidence of smoking as a risk factor for
      periodontal disease. 

PMID- 23873200
TI  - Effect of a school-based hand washing promotion program on knowledge and hand
      washing behavior of girl students in a middle school of Delhi.
AB  - The intervention study was conducted in a school of New Delhi to assess the
      effect of a school based hand-washing promotion program on knowledge and hand
      washing behavior among school children and extent of information sharing with
      parents. Intervention was carried out on randomly selected 300 students (100 each
      from 6th class to 8th class) with 281 students being part of the final analysis.
      Tools of the study were hand-washing questionnaire and household survey performa;
      essay, poster, slogan writing competition; classroom interactions. Data were
      analyzed in the SPSS 16.0 software and Mcnemar test and Student paired t-test
      were used. After the program, 95% felt that hand should be washed frequently.
      Overall, there was a significant improvement in the knowledge regarding hand
      washing and frequency of hand-washing practices after the intervention. 42%
      children shared this information with their parents. The intervention proved
      effective in improving awareness and highlights the potential of school for hand
      washing promotion activities. 

PMID- 23873201
TI  - Health seeking behavior of the mothers for the special care new-born unit
      discharged children: a comparative study.
AB  - Establishment of special care new-born units (SCNU) in hospitals not only serves
      to provide the intensive care to sick neonates, but presents with opportunities
      to enhance knowledge and modify attitude and practices of their parents through
      behavior change communication (BCC). A cross-sectional study was conducted in
      Dibrugarh District, Assam from January to June, 2011 to assess differences in
      health-care seeking behavior of these mothers from mothers of newborns who were
      born at home and mothers who had normal uneventful institutional deliveries.
      Mothers of 29 SCNU discharged, 34 institutions delivered and 26 home delivered
      children were interviewed using a semi-structured interview schedule and a
      knowledge, attitude and practice (KAP) survey tool. Mothers of children admitted
      to SCNU scored better in questions related to vaccination, contraception,
      protection of child from infections and cold and perceptions about traditional
      healers, but overall KAP scores in the three groups were not found significantly
      different. 

PMID- 23873202
TI  - Trend of syphilis in a tertiary care hospital, New Delhi: 2001-2009.

PMID- 23873203
TI  - Challenges in neurological practice in primary health-care facilities.

PMID- 23873204
TI  - Assessment of energy expenditure among obese and non-obese children in national
      capital territory of Delhi.

PMID- 23873205
TI  - Target-induced charge reduction of aptamers for visual detection of lysozyme
      based on positively charged gold nanoparticles.
AB  - Positively charged gold nanoparticles ((+)AuNPs) are electrostatically adsorbed
      on the negatively charged aptamers and the solution displays a blue color due to
      the aggregation of the (+)AuNPs, while the binding of the target lysozyme with
      the aptamers reduces the charge of the aptamers, which stabilizes the (+)AuNPs
      and the (+)AuNPs solution remains red in color. 

PMID- 23873206
TI  - Hydrothermal synthesis of high-quality thiol-stabilized CdTe(x)Se(1-x) alloyed
      quantum dots.
AB  - Alloyed semiconductor quantum dots (QDs) enriched the synthetic routes for
      engineering materials with unique structural and optical properties. High-quality
      thiol-stabilized CdTe(x)Se(1-x) alloyed QDs were synthesized through a facile and
      economic hydrothermal method at 120  degrees C, a relatively low temperature.
      These water-soluble QDs were prepared using different capping agents including 3
      mercaptopropionic acid (MPA) and L-cysteine (L-Cys). The photoluminescence (PL)
      intensity and stability of L-Cys-capped CdTe(x)Se(1-x) QDs were found to be
      higher than that of MPA-stabilized ones. The molar ratios of Se-to-Te upon
      preparation were adjusted for investigating the effect of composition on the
      properties of the resulting QDs. We also investigated the effect of the pH value
      of the reaction solution on the growth kinetics of the alloyed CdTe(x)Se(1-x)
      QDs. The resulting CdTe(x)Se(1-x) QDs were characterized by UV-vis absorbance and
      PL spectroscopy, powder X-ray diffraction, and transmission electron microscopy.
      Being coated with a CdS inorganic shell, the PL intensity and stability of the
      CdTe(x)Se(1-x)/CdS core-shell QDs were drastically enhanced, accompanied by the
      red-shift of the PL peak wavelength. Owing to the unique optical properties, the
      QDs hold great potential for application and have to be further exploited.

PMID- 23873207
TI  - Rapid and sensitive online determination of some selective alpha1-blockers by
      flow injection analysis with micelle-enhanced fluorescence detection.
AB  - A rapid, sensitive and selective flow injection analysis (FIA) method was
      developed for the determination of some selective alpha1-blockers including;
      terazosin (TER), doxazosin (DOX), prazosin (PRZ), and alfuzosin (ALF). The method
      was based on enhancement of the native fluorescence of the studied drugs in the
      presence of sodium dodecyl sulfate (SDS). The method was optimized for the buffer
      type, concentration and pH, surfactant type and concentration, flow rate and
      detection wavelengths in order to achieve the maximum sensitivity. The results
      showed that the best sensitivity was obtained by using SDS (10 mM) in phosphate
      buffer (20 mM, pH = 3), flow rate was 0.5 ml/min and the detector was set at
      lambdaex = 250 and lambdaem = 389. Under these optimum conditions there was a
      linear relationship between the concentration and the fluorescence intensity in
      the range from 5-400 ng ml(-) with correlation coefficient of more than 0.998.
      The detection and quantitation limits for the studied drugs by the proposed
      method were 3.2-11.9 ng ml(-1) and 10.8-39.7 ng ml(-1), respectively. The method
      was validated in accordance with the requirements of ICH guidelines and shown to
      be suitable for intended applications. Moreover, the binding constants for alpha1
      blockers -SDS system were determined using the adduct model. The proposed method
      has been applied successfully for the analysis of the pure forms for studied
      drugs and also their pharmaceutical formulations and the results were compared
      with official methods. 

PMID- 23873208
TI  - New insights on the 7-azaindole photophysics: the overlooked role of its non
      phototautomerizable hydrogen bonded complexes.
AB  - In this paper we explore the formation and the photophysical properties of the
      scarcely studied open hydrogen bonded aggregates of 7-Azaindole, 7AI. Thus, we
      have analyzed the influence that the increase of the 7AI concentration and the
      decrease of the temperature have on the 7AI photophysics. To help the
      interpretation of the results, the 7AI-Pyridine system has been used as the model
      for the analysis of the photophysical properties attributable to the open
      N(pyrrolic) - H . . . N(pyridinic) hydrogen bonded aggregates. Also, the hydrogen
      bond interactions have been studied by means of the atom in molecule approach
      from the Bader theory. Experimental and theoretical results support that the
      formation of open hydrogen bonded aggregates, (-7AI-)n with n >= 2 can
      efficiently compete with that of the profusely studied centro-symmetric cyclic
      dimer (7AI)2. Moreover, these aggregates suffer a proton-driven electron transfer
      process that strongly quenches their room temperature fluorescence and,
      therefore, masks their presence in the 7AI solutions. Therefore, because most of
      the studies on the 7AI photophysics have been interpreted without considering the
      existence of such aggregates and, more important, ignoring its quenching process,
      many conclusions obtained from these studies should be carefully revised.

PMID- 23873209
TI  - Elastic properties of functionalized carbon nanotubes.
AB  - We study the effects of covalent functionalization of single wall carbon
      nanotubes (CNT) on their elastic properties. We consider simple organic molecules
      -NH, -NH2, -CH2, -CH3, -OH attached to CNTs' surface at various densities. The
      studies are based on the first principles calculations in the framework of
      density functional theory. We have determined the changes in the geometry and the
      elastic moduli of the functionalized CNTs as a function of the density of
      adsorbed molecules. It turns out that elastic moduli diminish with increasing
      concentration of adsorbents, however, the functionalized CNTs remain strong
      enough to be suitable for reinforcement of composites. The strongest effect is
      observed for CNTs functionalized with -CH2 radical, where the Young's modulus of
      the functionalized system is 30% smaller than in the pristine CNTs. 

PMID- 23873210
TI  - The evaluation of the consistency of quantified assertions.
AB  - Consistency is a hallmark of rationality, and this article reports three
      experiments examining how reasoners determine the consistency of quantified
      assertions about the properties of individuals-for example, All of the actors are
      waiters. The mental model theory postulates that reasoners determine consistency
      by trying to construct a model of all of the assertions in a set. As the theory
      predicts, consistency is easier to establish when many different sorts of
      individuals satisfy the assertions (Exp. 1), when the predicted initial mental
      model satisfies them (Exp. 2), and otherwise when the model satisfying them is
      not too distant from the initial model, according to Levenshtein's metric (Exp.
      3). 

PMID- 23873211
TI  - Pathophysiology of coronary vascular remodeling: relationship with traditional
      risk factors for coronary artery disease.
AB  - The relationship between cardiovascular risk factors and vascular remodeling is a
      relatively new area of investigation. We discuss the various mechanisms by which
      cardiovascular risk factors cause vascular remodeling. Endothelial dysfunction,
      lipoprotein alterations, inflammation, and platelet activation are the mechanisms
      by which remodeling occurs. Plaque composition also plays an important role in
      directing remodeling. Plaque with extensive calcification is more likely to
      undergo constrictive remodeling. Positive and negative remodeling is based on how
      these factors coordinate and determine the direction of remodeling. Matrix
      metalloproteinases perform a crucial role in vascular remodeling. Advanced
      glycation end-products are key substances involved in the negative remodeling
      associated with diabetes. Remodeling in hypertension can be either eutrophic or
      hypertrophic. Endothelial dysfunction and low-grade inflammation lead to negative
      remodeling in hypertension. Dyslipidemia can be associated with either positive
      or negative remodeling. High high-density lipoprotein is associated with positive
      remodeling and high low-density lipoprotein with negative remodeling. Smoking
      causes endothelial dysfunction, increased oxidative stress, and decreased nitric
      oxide synthesis leading to inward remodeling. Aging also causes endothelial
      dysfunction and predisposes to negative remodeling. Knowledge of these
      associations can elucidate various clinical presentations and guide therapeutic
      choices in the future. 

PMID- 23873212
TI  - Proteostasis of polyglutamine varies among neurons and predicts
      neurodegeneration.
AB  - In polyglutamine (polyQ) diseases, only certain neurons die, despite widespread
      expression of the offending protein. PolyQ expansion may induce neurodegeneration
      by impairing proteostasis, but protein aggregation and toxicity tend to confound
      conventional measurements of protein stability. Here, we used optical pulse
      labeling to measure effects of polyQ expansions on the mean lifetime of a
      fragment of huntingtin, the protein that causes Huntington's disease, in living
      neurons. We show that polyQ expansion reduced the mean lifetime of mutant
      huntingtin within a given neuron and that the mean lifetime varied among neurons,
      indicating differences in their capacity to clear the polypeptide. We found that
      neuronal longevity is predicted by the mean lifetime of huntingtin, as cortical
      neurons cleared mutant huntingtin faster and lived longer than striatal neurons.
      Thus, cell type-specific differences in turnover capacity may contribute to
      cellular susceptibility to toxic proteins, and efforts to bolster proteostasis in
      Huntington's disease, such as protein clearance, could be neuroprotective. 

PMID- 23873213
TI  - G-protein signaling: A switch saves B12 radical status.

PMID- 23873214
TI  - A switch III motif relays signaling between a B12 enzyme and its G-protein
      chaperone.
AB  - Fidelity during cofactor assembly is essential for the proper functioning of
      metalloenzymes and is ensured by specific chaperones. MeaB, a G-protein chaperone
      for the coenzyme B12-dependent radical enzyme methylmalonyl-CoA mutase (MCM),
      uses the energy of GTP binding, hydrolysis or both to regulate cofactor loading
      into MCM, protect MCM from inactivation and rescue MCM that is inactivated during
      turnover. Typically, G proteins signal to client proteins using the
      conformationally mobile switch I and II loops. Crystallographic snapshots of MeaB
      reported herein reveal a new switch III element that has substantial
      conformational plasticity. Using alanine-scanning mutagenesis, we demonstrate
      that the switch III motif is critical for bidirectional signal transmission of
      the GTPase-activating protein activity of MCM and the chaperone functions of MeaB
      in the MeaB-MCM complex. Mutations in the switch III loop identified in patients
      corrupt this interprotein communication and lead to methylmalonic aciduria, an
      inborn error of metabolism. 

PMID- 23873215
TI  - RNA-binding proteins associated with desiccation during seed development in rice.
AB  - Long-lived mRNAs stored in mature seeds can remain active for long periods even
      if seeds undergo severe desiccation. They are then translated at the initiation
      of germination. To clarify the mechanism for stabilization of long-lived mRNAs
      during seed desiccation, fluctuations in RNA-binding protein (RBP) profiles that
      occur during seed formation in rice were analyzed. Proteomic analysis revealed
      that glycine-rich RBP 1A (GRP1A) is a highly abundant RBP in mature rice seeds.
      In addition, real-time RT-PCR analysis showed that putative RBP RZ-1A (RZ-1A) is
      seed specific. Moreover, transcripts of these two RBPs were clearly up-regulated
      during desiccation in rice seeds. The features of these two RBPs resemble those
      of late embryogenesis abundant proteins that function as molecular chaperones in
      dry seeds. Therefore, GRP1A and RZ-1A may have important roles in the stability
      of long-lived mRNAs in rice seeds.

PMID- 23873216
TI  - Mitral and tricuspid valve surgery for Coffin-Lowry syndrome.
AB  - Coffin-Lowry syndrome is a rare X-linked disorder characterized by craniofacial
      and skeletal abnormalities, mental retardation, short stature, and hypotonia. An
      18-year-old man with morphologic features characteristic of Coffin-Lowry syndrome
      was referred to our institution for valve disease surgery for worsening cardiac
      failure. Echocardiography showed severe mitral valve regurgitation associated
      with tricuspid valve regurgitation. Mitral valve implantation with a biological
      valve and tricuspid annular plication with a ring was performed. The ascending
      aorta was hypoplastic. Both the mitral papillary muscle originating near the
      mitral annulus and the chordae were shortened. The patient's postoperative course
      was uneventful and his cardiac failure improved.

PMID- 23873217
TI  - The association of cytopenias and weight loss with hepatitis C virus virologic
      response in HIV/HCV-coinfected patients treated with PEG-IFN and RBV.
AB  - BACKGROUND: Pegylated interferon (PEG-IFN)/ribavirin (RBV)-related cytopenias
      have been associated with improved virological outcomes among hepatitis C virus
      (HCV)-monoinfected patients. This analysis evaluated PEG-IFN/RBV-related
      cytopenias with virological responses among HIV/HCV-coinfected patients. METHODS:
      Pooled data from PARADIGM and AIDS Pegasys Ribavirin International CO-infection
      Trial (APRICOT) trials of HIV/HCV-infected patients treated with PEG-IFN/RBV.
      Virologic response was categorized as HCV RNA detectable (end of treatment
      nonresponders [ET-NR]) or nondetectable (end of treatment responders [ETR]).
      Declines in hemoglobin (Hgb), platelets, neutrophils, lymphocytes, and weight
      between the groups were compared via analysis of covariance and Cochran-Mantel
      Haenszel test. RESULTS: A total of 474 patients, 291 ET-NR and 183 ETR (67
      relapsers, 116 with sustained virologic response), 81% male, 52% Caucasian, 88%
      noncirrhotic, and 67% nondetectable HIV. The ETR experienced greater Hgb declines
      (>=3.0 g/dL) from baseline (73.8% versus 55.0%; P < .0001), neutrophils <=1 and
      <= 0.5 * 10(9)/L (66.1% versus 56.4%; P = .0334 and 42.6% versus 33.3%; P =
      .0312, respectively), and lymphocytes <=1.5 and <=0.5 * 10(9)/L (99.5% versus
      87.6%; P < .0001 and 24.6% versus 14.9%; P =.0079, respectively). CONCLUSIONS:
      The HIV/HCV-coinfected patients with ETR experienced greater declines in Hgb,
      neutrophils, and lymphocytes than the ET-NR patients.

PMID- 23873218
TI  - Depressive Symptoms and Associated Factors among People Living with HIV/AIDS.
AB  - The purpose of this study was to evaluate the prevalence of depressive symptoms
      and associated variables among people living with HIV/AIDS (PLWHA) in a
      specialized treatment center in a city located in southern Brazil. A cross
      sectional study was conducted using the Beck Depression Inventory to assess the
      presence of depressive symptoms. The prevalence of depressive symptoms was 53.5%
      among the surveyed population, which supports the idea that depressive symptoms
      are more common among PLWHA, mainly if compared with the general population. It
      was observed that 57.7% of the study participants were with depressive symptoms
      and did not take any psychiatric medication and 100% did not undergo
      psychotherapy, which indicates undertreatment. There was no statistically
      significant difference in the mean CD4 count between patients with depressive
      symptoms (484.1  +/-  353) and patients without depressive symptoms (528.4  +/- 
      263). Further actions should be taken to improve the care for PLWHA. The
      interface between psychology, psychiatry, and internal medicine is of utmost
      importance to provide a more humanized care, in which the psychosocial,
      psychological, and psychiatric aspects are not neglected.

PMID- 23873219
TI  - "Notify your partners--it's the law": HIV providers and mandatory disclosure.
AB  - HIV care providers in the United States must counsel clients about disclosure to
      sexual partners and report anyone who is suspected of noncompliance. This study
      compared provider attitudes and practices in relation to counseling clients about
      mandatory disclosure in North Carolina and Alabama, the 2 states with similar HIV
      epidemiology but different laws for HIV control. Personal interviews were
      conducted with 20 providers in each state (n = 40). The results were analyzed in
      a qualitative, cross-comparison method to identify patterns of convergence or
      difference. Providers in both states believed that clients often failed to notify
      sexual partners and were secretive if questioned about disclosure. Differences in
      counseling styles and procedures for each state were noteworthy. Compared to
      Alabama, North Carolina had harsher penalties for nondisclosure, stricter and
      more standardized procedures for counseling, and providers expressed greater
      support for HIV criminalization. Although most North Carolina providers viewed
      the stricter standards as beneficial for HIV care and control, Alabama providers
      were likely to view such standards as a barrier to patient care. These results
      indicated a direct relation between state HIV law, provider attitudes, and
      counseling procedures for mandatory disclosure.

PMID- 23873220
TI  - Oxidative stress increased hepatotoxicity induced by nano-titanium dioxide in BRL
      3A cells and Sprague-Dawley rats.
AB  - Extensive studies have shown that titanium dioxide (TiO2 ) nanomaterials (NMs)
      can cause toxicity in vitro and in vivo under normal conditions. However, an
      adverse effect induced by nano-TiO2 in many diseased conditions, typically
      characterized by oxidative stress (OS), remains unknown. We investigated the
      toxicity of nano-TiO2 in rat liver cells (BRL-3A) and Sprague-Dawley (SD) rat
      livers under OS conditions, which were generated using hydrogen peroxide (H2 O2 )
      in vitro and alloxan in vivo, respectively. In vitro results showed that cell
      death ratios after nano-TiO2 exposure were significantly enhanced (up to 2.62
      fold) in BRL-3A cells under OS conditions, compared with normal controls.
      Significant interactions between OS conditions and nano-TiO2 resulted in the
      rapid G0/G1 to S phase transition and G2/M arrest, which were opposite to G0/G1
      phase arrest in cells after NMs exposure only. In vivo results showed that
      obvious pathological changes in rat livers and the increased activities of four
      enzymes (i.e. aspartate aminotransferase, alanine aminotransferase, lactate
      dehydrogenase and alkaline phosphatase) owing to liver damage after nano-TiO2
      exposure under OS conditions, compared with their healthy controls. In addition,
      compared with increased hepatotoxicity after nano-TiO2 exposure, micro-TiO2
      showed no adverse effects to cells and rat livers under OS conditions. Our
      results suggested that OS conditions synergistically increase nano-TiO2 induced
      toxicity in vitro and in vivo, indicating that the evaluation of nanotoxicity
      under OS conditions is essentially needed prior to various applications of NMs in
      foods, cosmetics and potential treatment of diseases.

PMID- 23873221
TI  - Barriers to healthy-lifestyle participation in stroke: consumer participation in
      secondary prevention design.
AB  - The aim of the study was to explore community-dwelling stroke patients' perceived
      barriers to healthy-lifestyle participation for secondary disease prevention, as
      well as their preferred means for risk-reduction information dissemination and
      motivators to participation in healthy-lifestyle interventions. Four focus groups
      (5-6 stroke survivors per group) were defined from community support groups. Key
      questions addressed barriers to healthy-lifestyle adoption, preferred methods for
      receiving information and factors that would engage participants in a risk
      reduction programme. Groups were audiotaped, transcribed verbatim and analysed
      for thematic content using a framework approach. Twenty-two participants, 12 men,
      10 women, mean age 71.4 (53-87) years, were included in the study. Three
      overarching themes emerged as barriers to healthy-lifestyle participation:
      physical, mental and environmental. Exercise participation difficulties spread
      across all three themes; healthy eating and smoking cessation concentrated in
      environmental and mental dimensions. Talks (discussions) were noted as
      participants' preferred method of information provision. Risk-reduction
      programmes considered attractive were stroke specific, convenient and delivered
      by healthcare professionals and involved both social and exercise components.
      Many stroke patients appear unable to adopt healthy-lifestyle changes through
      advice alone because of physical, mental and environmental barriers. Risk
      reduction programmes including interactive education should be specifically
      tailored to address barriers currently experienced and extend beyond the stroke
      survivor to others in their environment who influence lifestyle choices. 

PMID- 23873222
TI  - Rehabilitation of patients with obstructive sleep apnea syndrome.
AB  - The current treatment of obstructive sleep apnea syndrome (OSAS) focuses on
      alleviation of symptoms by increasing airway patency during sleep through
      positive airway pressure, oral appliances, changes in sleep position, weight
      loss, or surgical treatment. Continuous positive airway pressure (CPAP) is
      currently the treatment of choice and prevents upper airway obstruction,
      resulting in improved sleep architecture and daytime symptoms. Despite proven
      efficacy, adherence to CPAP treatment is still not efficient. The new methods of
      rehabilitation (exercise training programs, hypoglossal nerve stimulation) for
      patients with OSAS are currently modified. The aim of the present study was to
      present recent developments in the field of selected aspects of rehabilitation in
      patients with OSAS. Database search was focused on exercise training programs and
      electrostimulation of genioglossus muscle. The search for articles on the
      rehabilitation interventions for OSAS was performed using the PubMed database
      from 1966 to 2013. Most of the findings have shown beneficial effects of
      rehabilitation. In detail, we describe the recent developments and potential
      adverse effects of electrostimulation and physical exercises. According to the
      results of studies presented, the above therapy might support conventional
      treatment or may be an alternative for patients with poor compliance to CPAP
      therapy, mandibular advancement devices, or ineffective results of surgical
      procedures as well. 

PMID- 23873223
TI  - Effect of muscle strength on gait in hemodialysis patients with and without
      diabetes.
AB  - There is minimal data on the gait of hemodialysis (HD) patients with and without
      diabetes. This investigation examined spatiotemporal parameters of gait in HD
      patients with and without diabetes compared with age-matched, sex-matched, and
      BMI-matched controls. The effect of muscle weakness on gait in HD patients was
      also examined. Eighteen HD patients and 18 age-matched, sex-matched, and BMI
      matched controls completed two walking trials along a 7.9 m long pressure
      sensitive pathway. The HD participants were divided into groups based on their
      diabetic status (eight patients without diabetes and 10 with diabetes).
      Spatiotemporal markers of gait, including variability metrics, were determined.
      Knee strength was quantified only in the HD groups. Overall HD patients had a
      worse gait compared with controls (P<0.01). Furthermore, HD patients with
      diabetes had an elevated gait variability compared with those without diabetes,
      even after controlling for muscle strength (P<0.05). Further research is
      warranted to explore whether increases in lower extremity strength lead to
      improvements in gait in this population. 

PMID- 23873224
TI  - A general single-pot heating method for morphology, size and luminescence
      controllable synthesis of colloidal ZnO nanocrystals.
AB  - Here we demonstrate a single-pot heating approach for controllable synthesis of
      colloidal zinc oxide nanocrystals from zinc acetylacetonate. Such single-pot
      heating approaches are inherently amenable to large scale production. We have
      systematically studied the crystallization process, investigating the growth of
      nanocrystals and the influence of ligands on the morphology and luminescence of
      ZnO nanoparticles. We show that the morphology can be tuned to produce dendritic
      structures, nano-needles, nano-pinecones, nanoclusters, hexagonal pyramid
      nanoparticles and irregularly-shaped nanoparticles by varying the surfactants and
      co-surfactants used in synthesis. Moreover, we investigated the effect of ligands
      on the defect-related photoluminescence of ZnO NPs and demonstrated blue, green,
      white, yellow, and orange emission. This study opens up new possibilities for the
      practical use of ZnO nanomaterials for optoelectronic devices and bio-imaging. 

PMID- 23873225
TI  - High-performance flexible waveguiding photovoltaics.
AB  - The use of flat-plane solar concentrators is an effective approach toward
      collecting sunlight economically and without sun trackers. The optical
      concentrators are, however, usually made of rigid glass or plastics having
      limited flexibility, potentially restricting their applicability. In this
      communication, we describe flexible waveguiding photovoltaics (FWPVs) that
      exhibit high optical efficiencies and great mechanical flexibility. We
      constructed these FWPVs by integrating poly-Si solar cells, a soft
      polydimethylsiloxane (PDMS) waveguide, and a TiO2-doped backside reflector.
      Optical microstructures that increase the light harvesting ability of the FWPVs
      can be fabricated readily, through soft lithography, on the top surface of the
      PDMS waveguide. Our optimized structure displayed an optical efficiency of
      greater than 42% and a certified power conversion efficiency (PCE) of 5.57%, with
      a projected PCE as high as approximately 18%. This approach might open new
      avenues for the harvesting of solar energy at low cost with efficient,
      mechanically flexible photovoltaics.

PMID- 23873226
TI  - Effect of spine fellow training on operative outcomes, affirming graduated
      responsibility.
AB  - STUDY DESIGN: Retrospective review of prospectively collected surgical data.
      OBJECTIVE: This study sought to determine the effect of fellow education during
      the course of the academic year (August-July) on surgical outcomes in adolescent
      idiopathic scoliosis. One surgeon and one type of surgery were chosen to minimize
      confounding factors. SUMMARY OF BACKGROUND DATA: Educating and training the next
      generation of physicians and surgeons is necessary for the survival and
      continuation of medical care. There has been recent momentum to document
      scientifically that medical education is safe. Spine surgery is complex and
      demanding, with a steep learning curve, making it an ideal model to detect any
      potential negative impact of medical education. METHODS:  SUBJECTS: adolescent
      patients undergoing posterior spinal surgery, between August 2007 and July 2010,
      by a single senior surgeon at one institution with a fellow as the only surgical
      assistant. Demographic and perioperative data were collected and then segmented
      by surgical date into quarters according to the rotations of the academic year.
      One fellow was included in each quarter during the 4 years, resulting in 16
      fellows across the 4 quarters. An analysis of variance model was used to assess
      differences in operative time, blood loss, length of stay, and complications
      between the quarters of the year. RESULTS: There were no significant differences
      between the groups regarding age, sex, or Lenke curve type. No statistically
      significant differences were found between the 4 quarters of the fellowship year
      for estimated blood loss, use of cell saver, length of stay, operative time, and
      complication rate. CONCLUSION: This study is the first to show that fellow
      education during the course of the academic year did not impact the patient
      outcomes studied. It is clear that while there is significant academic benefit
      for the fellows as they complete their spine fellowship, there is no negative
      impact for patients. LEVEL OF EVIDENCE: 4.

PMID- 23873227
TI  - Tissue-engineered bone formation in vivo for artificial laminae of the vertebral
      arch using beta-tricalcium phosphate bioceramics seeded with mesenchymal stem
      cells.
AB  - STUDY DESIGN: A rabbit laminectomy model was used to evaluate the efficacy of
      artificial laminae of vertebral arch using bone marrow-derived mesenchymal stem
      cells (MSCs) transplanted in porous beta-calcium phosphates (beta-TCP)
      bioceramics. OBJECTIVE: The aim of this study was to establish artificial lamina
      of the vertebral arch for bone tissue engineering using beta-TCP bioceramics
      seeded with MSCs in a rabbit model of decompressive laminectomy. SUMMARY OF
      BACKGROUND DATA: Decompressive laminectomy may induce various degrees of scar
      tissue and adhesion formation in the epidural space, and thus is the most common
      cause of failed back surgery syndrome. However, there is no effective method of
      bone defect treatment to control and reduce the scar tissue formation. METHODS:
      MSCs were harvested from New Zealand rabbits (2-week old) by femoral bone marrow
      extraction. These cells were seeded into porous beta-TCP bioceramics and
      cultivated for up to 3 weeks in the presence of osteogenic supplements. Segmental
      defects (20 * 8 mm) were created in 48 adult New Zealand rabbits that underwent
      laminectomy at the L5 to L6 levels. The animals were transplanted with cell media
      (control), beta-TCP bioceramics (group I), or MSC-loaded beta-TCP bioceramics
      (group II). Bone formation was evaluated after operation using scanning electron
      microscopy, computed tomography, magnetic resonance imaging, histomorphometry,
      and immunohistochemistry. RESULTS: Scanning electron microscopy showed that MSCs
      filled the pores and surfaces of bioceramics in MSC-loaded beta-TCP. In addition,
      significant increases in bone formation were observed in group II compared with
      other groups. Computed tomography and magnetic resonance imaging at 16 weeks
      showed that the artificial lamina of the vertebral arch was successfully formed.
      Hematoxylin-eosin and Masson trichrome staining were used to show the artificial
      laminae of the vertebral arch and the degraded bioceramics. In addition,
      immunohistochemistry results showed that the expression of bone morphogenetic
      protein-2 increased significantly in group II compared with group I at 2,4, and 8
      weeks after implantation (P < 0.05). CONCLUSION: beta-TCP bioceramics seeded with
      MSCs are a promising source of tissue-engineered bone for the artificial lamina
      of the vertebral arch.

PMID- 23873228
TI  - Anterior release internal distraction and posterior spinal fusion for severe and
      rigid scoliosis.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To report on the results of
      anterior release, posterior internal distraction (with or without further
      distraction), and subsequent posterior spinal fusion for severe and rigid
      scoliosis. SUMMARY OF BACKGROUND DATA: For severe and rigid scoliosis,
      conventional procedures, such as posterior instrumentation combined with an
      anterior release, enable limited correction. Posterior vertebral column resection
      brings better correction but with a high rate of neurological complications or
      intraoperative neurological events. METHODS: A total of 15 patients with severe
      and rigid scoliosis who underwent anterior release, posterior internal
      distraction (with or without further distraction), and subsequent posterior
      spinal fusion were retrospectively reviewed after a minimum follow-up of 2 years.
      The radiographical parameters were evaluated, and clinical records were reviewed.
      RESULTS: The average number of anteriorly removed discs was 4.1. Average
      posterior fusion length comprised 14.3 vertebrae. Overall, internal distraction
      corrected the mean Cobb angle by 58.1% (from 105.1 degrees  to 44.2 degrees )
      compared with the initial curve magnitude. The mean preoperative scoliosis of
      105.1 degrees  was corrected to 27.5 degrees  (74.3% correction) at the most
      recent follow-up. The correction rate of the proximal thoracic and thoracolumbar
      or lumbar curves was 48.1% and 82.1%, respectively. The preoperative thoracic
      kyphosis of 62.3 degrees  was corrected to 33.8 degrees  at the most recent
      follow-up. The preoperative lumbar lordosis of -66.1 degrees  was corrected to 
      46.3 degrees  at the most recent follow-up. The mean preoperative coronal
      imbalance of 0.8 cm improved to 0.5 cm at the most recent follow-up, and sagittal
      imbalance of 0.3 cm improved to 0.2 cm. Transient dyspnea occurred in one patient
      after the initial surgery and subsequently resolved. Two patients complained of
      concave soft-tissue pain after the first distraction. There were no neurological
      complications. CONCLUSION: Anterior release, posterior internal distraction, and
      subsequent posterior spinal fusion provide an effective alternative for severe
      and rigid scoliosis. LEVEL OF EVIDENCE: 4.

PMID- 23873229
TI  - Change of aortic length after closing-opening wedge osteotomy for patients with
      ankylosing spondylitis with thoracolumbar kyphosis: a computed tomographic study.
AB  - STUDY DESIGN: A computed tomographic study. OBJECTIVE: To investigate the change
      in aortic length in patients with ankylosing spondylitis (AS) with thoracolumbar
      kyphosis after closing-opening wedge osteotomy (COWO). SUMMARY OF BACKGROUND
      DATA: Several previous studies reported that COWO can effectively correct severe
      thoracolumbar kyphosis caused by AS. However, one disadvantage of COWO is
      elongation of the aorta, which increases the risk of aortic injury. To date, no
      studies have analyzed the alteration in aortic length in patients with AS
      undergoing COWO for thoracolumbar kyphosis. METHODS: A total of 21 consecutive
      patients with AS with a mean age of 38.9 years undergoing COWO for the correction
      of thoracolumbar kyphosis were retrospectively studied. Radiographical
      measurements included global kyphosis, thoracic kyphosis, lumbar lordosis, angle
      of fusion levels, local kyphosis, and anterior height of the osteotomized
      vertebra. The computed tomographic scans of the spine were used to measure the
      aortic diameter (at the site of the osteotomy) and length (the length between the
      superior endplate of the upper instrumented vertebra and the inferior endplate of
      L4). RESULTS: The aortic length increased by an average of 2.2 cm
      postoperatively. Significant changes in global kyphosis, local kyphosis, angle of
      fusion levels, lumbar lordosis, anterior height of the osteotomized vertebra, and
      aortic diameter at the site of the osteotomy were observed (P < 0.01).
      Significant correlation was noted between aortic length and changes in global
      kyphosis (r = 0.525, P = 0.015), local kyphosis (r = 0.654, P = 0.001), angle of
      fusion levels (r = 0.634, P = 0.002), and lumbar lordosis (r = 0.538, P = 0.012).
      CONCLUSION: Aortic lengthening after COWO for correction of kyphosis was
      quantitatively confirmed by this study. Spine surgeons should be aware of the
      potential risk for the development of aortic injury in patients with AS
      undergoing COWO for the correction of thoracolumbar kyphosis. LEVEL OF EVIDENCE:
      4.

PMID- 23873230
TI  - Rheological and dynamic integrity of simulated degenerated disc and consequences
      after cross-linker augmentation.
AB  - STUDY DESIGN: An in situ study using whole-organ culture system. OBJECTIVE: To
      study the effect of disc degeneration at different stages on its rheological and
      dynamic properties and to investigate the efficacy of exogenous cross-linking
      therapy. SUMMARY OF BACKGROUND DATA: Disc degeneration can involve protein
      denaturation or microdefects to the disc's collagen fiber network. A disc
      degeneration model using whole-organ culture technique can be effectively used
      for the screening of treatments of degenerated discs. Exogenous cross-linking
      therapy has been shown to enhance the mechanical properties of the disc by cross
      linking collagen. However, the efficacy of this therapy on the degenerated disc
      is unclear. METHODS: A total of 40 porcine thoracic discs were assigned to 5
      groups: intact discs, moderately degenerated discs, moderately degenerated discs
      with cross-linker augmentation, severely degenerated discs, and severely
      degenerated discs with cross-linker augmentation. The disc degeneration was
      simulated by trypsin digestion and mechanical fatigue loading. Rheological
      properties, dynamic properties, water content, and histological analysis were
      conducted after a 7-day incubation. RESULTS: The mechanical properties of
      moderate degenerated discs significantly decrease both in rheological and dynamic
      properties, and laminate structure disorganization was observed. Mechanical
      defects of severely degenerated discs resulted in disc height loss, an increase
      in the aggregate modulus and stiffness modulus, and a decrease in the damping
      coefficient, hydraulic permeability, and water content. Cross-linker augmentation
      significantly recovered mechanical properties of moderately degenerated discs and
      restored the water content compared with the intact disc. However, the
      augmentation did not fully repair the severely degenerated discs. CONCLUSION:
      Trypsin-induced extracellular matrix damage resulted in a change of the disc's
      biomechanics. Cross-linker augmentation recovers the rheological and dynamic
      properties of moderately degenerated discs but not of the severely degenerated
      discs. The genipin cross-linker may be able to improve the proteoglycan depletion
      effect in the nucleus pulposus but may not be effective to restore the structural
      damage in the collagen molecule of the anulus fibrosus.

PMID- 23873231
TI  - An institutional six-year trend analysis of the neurological outcome after
      lateral lumbar interbody fusion: a 6-year trend analysis of a single institution.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the proportional
      trend over time of neurological deficits after lateral lumbar interbody fusion
      (LLIF) at a single institution. SUMMARY OF BACKGROUND DATA: Because lumbar nerve
      roots converge to run as the lumbar plexus within or less frequently underneath
      the posterior part of the psoas muscle, they are prone to iatrogenic damage
      during the transpsoas approach in LLIF, and adverse postoperative neurological
      sequelae remain a major concern. METHODS: The electronic medical records and
      office notes of 451 patients who had consecutively undergone LLIF between March
      2006 and April 2012 at a single institution were retrospectively reviewed for
      reports on postoperative neurological deficits. RESULTS: A total of 293 patients
      (173 females and 120 males) met the study inclusion criteria and were followed
      postoperatively for a mean period of 15.4 +/- 9.2 months (range: 6-53 mo). The
      number of included patients who underwent LLIF at our institution was 47 in the
      years 2006 to 2008 (group A), 155 in 2009 to 2010 (group B), and 91 in 2011 to
      2012 (group C). Our data indicate a decreasing proportional trend during the past
      6 years for postoperative sensory deficits (SDs), motor deficits (MDs), and
      anterior thigh pain (TP). The decreasing trends were statistically significant
      for the proportion of SDs in the immediate postoperative setting (P = 0.018) and
      close to statistically significant for SDs at last follow-up (P = 0.126), TP
      immediately after surgery (P = 0.098), and TP at last follow-up (P = 0.136).
      CONCLUSION: To the authors' best knowledge, this study constitutes the largest
      series of this sort to date, with regard to both sample size and study period.
      The present data indicate a decreasing proportional trend over time for SDs, MDs,
      and anterior TP, which can be considered a representation of an institutional
      learning curve during a 6-year time period of performing LLIF.

PMID- 23873232
TI  - Biomechanics of spinal hemiepiphysiodesis for fusionless scoliosis treatment
      using titanium implant.
AB  - STUDY DESIGN: In vitro study of the effect of hemiepiphyseal implant on
      biomechanical properties of porcine thoracic motion segments. OBJECTIVE:
      Determine whether implantation of a titanium clip-screw construct alters spine
      biomechanical properties. SUMMARY OF BACKGROUND DATA: Growth modification is
      under investigation as a treatment of early adolescent idiopathic scoliosis.
      Biomechanical property changes due to device implantation are essential to
      characterize immediate postoperative treatment effects. METHODS: In vitro
      biomechanical tests were conducted on 18 thoracic functional spinal units.
      Specimens were tested before and after implantation of a clip-screw construct in
      lateral bending, flexion-extension, or axial rotation (n = 6 per loading
      direction). Pure moments were applied, and range of motion, stiffness, and
      neutral zone were measured. Axial translations were determined bilaterally.
      RESULTS: Implantation of the clip-screw construct decreased range of motion in
      lateral bending by 19% (P < 0.0003), flexion-extension by 11% (P < 0.04), and
      axial rotation by 8%. Mean stiffness in lateral bending toward and away from the
      treated side increased by 20% (P < 0.007) and 33%, respectively. In flexion and
      extension, mean stiffness increased by 10% and 16%, respectively. Treatment
      decreased the neutral zone in lateral bending toward and away from the
      instrumented side by 30% (P < 0.0003) and 47% (P < 0.02), respectively. In
      flexion and extension, neutral zone decreased by 20% (P < 0.04) and 26% (P <
      0.007), respectively. In axial rotation toward and away from the treated side,
      mean neutral zone decreased by 22% (P < 0.04) and 7%, respectively. Range of
      axial translation decreased on the ipsilateral side by 49% (P < 0.001) and
      increased on the contralateral side by 17%. CONCLUSION: Implantation of a
      titanium clip-screw construct decreased range of motion by less than one-fifth,
      increased stiffness by one-third or less, and decreased the neutral zone by less
      than one-half. Range of axial translation decreased on the instrumented side and
      increased contralaterally. This study suggests that most of the flexibility of
      the spine is preserved in the immediate postoperative period after implantation
      of the spinal hemiepiphyseal construct.

PMID- 23873233
TI  - Induction of SHP2 deficiency in chondrocytes causes severe scoliosis and kyphosis
      in mice.
AB  - STUDY DESIGN: Genetic engineering techniques were used to develop an animal model
      of juvenile scoliosis during a postnatal skeletal-growth stage. OBJECTIVE: To
      investigate the effect of targeted SHP2 (Src homology-2) deficiency in
      chondrocytes on the development of scoliosis during a juvenile growth stage in
      mice. SUMMARY OF BACKGROUND DATA: Juvenile idiopathic scoliosis can lead to
      progressive severe spinal deformity. The pathophysiology and molecular mechanisms
      responsible for the deformity are unknown. Here, we investigated the role of SHP2
      deficiency in chondrocytes as a potential cause of juvenile scoliosis. METHODS:
      Genetically engineered mice with inducible deletion of SHP2 in chondrocytes were
      generated. The SHP2 function in chondrocytes was inactivated during a juvenile
      growth stage from the mouse age of 4 weeks. Radiographical, micro-computed
      tomographic, and histological assessments were used to analyze spinal changes.
      RESULTS: When SHP2 deficiency was induced during the juvenile stage, a
      progressive kyphoscoliotic deformity (thoracic lordosis and thoracolumbar
      kyphoscoliosis) developed within 2 weeks of the initiation of SHP2 deficiency.
      The 3-dimensional micro-computed tomography analysis confirmed the kyphoscoliotic
      deformity with a rotational deformity of the spine and osteophyte formation. The
      histological analysis revealed disorganization of the vertebral growth plate
      cartilage. Interestingly, when SHP2 was disrupted during the adolescent to adult
      stages, no spinal deformity developed. CONCLUSION: SHP2 plays an important role
      in normal spine development during skeletal maturation. Chondrocyte-specific
      deletion of SHP2 at a juvenile stage produced a kyphoscoliotic deformity. This
      new mouse model will be useful for future investigations of the role of SHP2
      deficiency in chondrocytes as a mechanism leading to the development of juvenile
      scoliosis. LEVEL OF EVIDENCE: N/A.

PMID- 23873234
TI  - United States hospital admissions for lumbar spinal stenosis: racial and ethnic
      differences, 2000 through 2009.
AB  - STUDY DESIGN: Retrospective analysis of Nationwide Inpatient Sample and US Census
      data. OBJECTIVE: To (1) document national trends in surgical hospitalizations
      with the primary diagnosis of lumbar spinal stenosis from 2000 through 2009; and
      (2) evaluate how those trends relate to race and ethnicity. SUMMARY OF BACKGROUND
      DATA: In the United States, the rate of lumbar spinal stenosis surgery is
      increasing, and understanding how changing demographic trends impact
      hospitalization rates for this surgery is important. METHODS: Multivariable
      regression models were used to determine associations between race and ethnicity
      and the rates of surgical hospitalization for lumbar spinal stenosis. All models
      were adjusted for age, sex, insurance, income status, geographical location, and
      comorbidities. RESULTS: From 2000 through 2009, the overall surgical
      hospitalization rate increased by 30%. Surgical hospitalization rates for lumbar
      spinal stenosis in the United States varied substantially across racial and
      ethnic groups. In 2009, white, non-Hispanics had the highest rate (1.074 per
      1000) compared with black, non-Hispanics (0.558 per 1000; P< 0.001), and
      Hispanics (0.339 per 1000; P< 0.001). The relative differences persisted across
      time. CONCLUSION: There were substantial differences in rates of surgical
      hospitalization among individuals of different racial and ethnic groups. Possible
      causes were (1) differences in clinical decision making among spine care
      providers with regard to offering surgical care to minority populations; (2)
      differences in access to care because of financial, educational, or geographical
      barriers; and (3) differences in attitudes toward surgical care among those of
      different racial and ethnic groups. LEVEL OF EVIDENCE: 3.

PMID- 23873235
TI  - Cell based therapies as compared to autologous bone grafts for spinal
      arthrodesis.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To compare the clinical outcome of
      cell based grafts combined with bone extenders to autologous bone grafts. SUMMARY
      OF BACKGROUND DATA: Alternative graft options that combine mesenchymal stem cells
      (MSCs) and bone marrow aspirate (BMA) with synthetic or allograft scaffolds have
      been recently used in several animal and clinical studies. METHODS: This
      systematic review of the literature addresses the following key questions (KQs):
      (1) Does the use of MSCs or BMA combined with synthetic or allograft extenders
      contribute to thoracolumbar fusion rates that are comparable with the rates
      achieved by the use of iliac crest graft? (2) Are these fusion rates comparable
      with those of local bone graft (LBG)? (3) Does the addition of MSCs or BMA to
      iliac crest bone graft or LBG contribute to better throracolumbar fusion rates?
      (4) Are the cervical spine fusion outcomes achieved by the use of SCM or BMA with
      synthetic or allograft scaffolds comparable with the iliac crest bone graft or
      LBG outcomes? (5) Was there any difference in terms of fusion rates, when MSCs
      were compared with BMA? RESULTS: For KQ1, 4 level II, III studies used iliac
      crest bone graft as control. The results of these studies were inconsistent, and
      the overall body of evidence was found insufficient. Three, level II, III studies
      were identified for KQ2. Comparable fusion rates were demonstrated between LBG
      and BMA combined with calcium phosphate or collagen carrier. The overall body of
      evidence was found weak. For KQ3, one level III study was found. No significant
      difference was found in the fusion rates. No studies met the criteria for KQ4, 5.
      CONCLUSION: The currently available evidence is insufficient to support the use
      of MSCs or BMA combined with synthetic or allograft materials as a substitute or
      supplementary graft to autologous bone graft. LEVEL OF EVIDENCE: 2.

PMID- 23873236
TI  - Incidence and risk factors for dysphagia after anterior cervical fusion.
AB  - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To determine the
      national incidence, mortality, and risk factors for dysphagia associated with
      anterior cervical spinal fusion surgery in the United States. SUMMARY OF
      BACKGROUND DATA: Dysphagia is a known complication associated with anterior
      cervical fusion (ACF). A population-based database was analyzed to characterize
      the incidence of dysphagia in terms of demographics, mortality, and risk factors
      associated with ACF. METHODS: Data from the Nationwide Inpatient Sample of the
      Healthcare Cost and Utilization Project were obtained from 2002 to 2009. Patients
      undergoing ACF for cervical myelopathy and/or radiculopathy were identified and
      separated into cohorts (1- to 2-level and 3+-level fusions), and incidences of
      dysphagia were identified. Demographics, length of stay, costs, mortality, and
      use of bone morphogenetic proteins (BMPs) were assessed. Statistical data were
      analyzed in SPSS (version 20), using the Student t test for discrete variables
      and the chi test for categorical data. Binomial logistic regression was used to
      identify independent predictors of dysphagia. A P value of less than 0.001 was
      used to denote significance. RESULTS: A total of 159,590 ACF cases were
      identified of which 139,434 were 1- to 2-level ACF and 20,156 were 3+-level ACF.
      The incidence of dysphagia in the 3+-level ACF group was double that of the 1- to
      2-level ACF group (44.8 vs. 22.4 per 1000; P < 0.001). Patients with dysphagia
      were significantly older than patients without dysphagia (P < 0.001). Dysphagia
      was more common in males undergoing 1- to 2-level ACF (P < 0.001). BMP was used
      more frequently for patients with dysphagia in the 1- to 2-level ACF group (9.4%
      vs. 7.2% of cases; P < 0.001). Logistic regression analysis demonstrated that
      independent predictors for dysphagia included age (>=65 yr), male sex, 3+-level
      fusion, BMP use, and preoperative patient comorbidities. CONCLUSION: Dysphagia
      occurs twice as often after 3+-level ACF compared with 1- to 2-level ACF.
      Utilization of BMP was also linked to an increased incidence of dysphagia in the
      1- to 2-level ACF group. Regardless of the number of levels fused, patients
      experiencing dysphagia had increased age, comorbid risk factors,
      hospitalizations, and costs. LEVEL OF EVIDENCE: 3.

PMID- 23873237
TI  - Loss in spinal motion from inclusion of a single midlumbar level in posterior
      spinal fusion for adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: Evaluate the impact of the distal
      fusion level on overall spine motion in patients with adolescent idiopathic
      scoliosis. SUMMARY OF BACKGROUND DATA: In the surgical treatment of adolescent
      idiopathic scoliosis, the impact of incorporating a single additional distal
      lumbar fusion level on residual spinal motion is unclear. This study uses
      radiographs and computerized motion capture technology to determine whether the
      addition of a single lumbar level in a posterior fusion construct produces a
      detectable alteration in spinal motion. METHODS: Twenty-three patients with
      adolescent idiopathic scoliosis were evaluated with standing radiographs and
      computerized motion analysis preoperatively and 1 year after fusion. Patients
      were divided into 2 groups: L1-L2 group (distal fusion ended at L1-L2) and an L3
      group (distal fusion ended at L3). Cobb angle, coronal vertical alignment,
      sagittal vertical alignment, thoracic kyphosis, and lumbar lordosis were measured
      from radiographs. Three-dimensional motion data were obtained for static standing
      and repeated bending or twisting motions. Statistical analysis was performed with
      Student t test, analysis of variance, and Fisher exact methods. RESULTS: Both the
      L1-L2 and L3 groups demonstrated loss of spinal motion compared with preoperative
      values. The L1-L2 group showed a significant loss of rotational motion but no
      significant loss of motion in the sagittal and coronal planes. The L3 group
      demonstrated significant loss of motion in both the coronal plane and the
      rotational plane. When the 2 groups were compared, the L3 group showed a
      significant loss of coronal plane bending (18 degrees  +/- 10 degrees , P =
      0.002). CONCLUSION: Distal extension of a posterior spinal fusion construct to
      include L3 results in a significant decrease in spine motion in at least one
      plane. Preservation of a single lumbar segment may improve overall spine motion
      in the short term and may have implications for the long-term health of the
      unfused spine. LEVEL OF EVIDENCE: 3.

PMID- 23873238
TI  - Measurement of blood perfusion in spinal metastases with dynamic contrast
      enhanced magnetic resonance imaging: evaluation of tumor response to radiation
      therapy.
AB  - STUDY DESIGN: This was a retrospective study focusing on dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) to assess treatment response in
      patients with spinal metastases. OBJECTIVE: To demonstrate DCE-MRI changes before
      and after radiation treatment and correlating with other imaging and clinical
      findings. SUMMARY OF BACKGROUND DATA: Currently, conventional imaging is limited
      in evaluating early treatment success or failure, which impacts patient care.
      METHODS: Consecutive patients with known spinal metastases underwent DCE-MRI
      before and after radiotherapy. Perfusion data on 19 lesions were analyzed.
      Radiotherapy was classified as success (n = 17) or failure (n = 2) on the basis
      of evidence of tumor contraction (n = 4), negative positron emission tomography
      (n = 2), or stability for more than 11 months (n = 11). Perfusion parameters
      blood plasma volume (Vp), time-dependent leakage (Ktrans), area under the curve,
      and peak enhancement were derived from the signal intensity-time curves and
      changes in parameter values from pre- to post-treatment were calculated. Curve
      morphologies were also qualitatively assessed in 13 pre- and 13 post-treatment
      scans. RESULTS: Vp was the strongest predictor of treatment response (false
      positive rate = 9.38 * 10 and false-negative rate = 0.055). All successfully
      treated lesions showed decreases in Vp, and the 2 treatment failures showed
      drastic increases in Vp. Changes in area under the curve and peak enhancement
      demonstrated similar relationships to the observed treatment response, whereas
      changes in Ktrans showed no significant relationship. Signal intensity curve
      morphologies also demonstrated specificity for active disease (11 of 13) and
      treated disease (8 of 13). CONCLUSION: Changes in perfusion, particularly Vp,
      reflect tumor responses to radiotherapy in spinal bone metastases. These changes
      were able to predict positive outcomes earlier than 6 months after treatment in
      16 of 17 tumors. The ability of DCE-MRI to detect early treatment response has
      the potential to improve patient care and outcome.

PMID- 23873239
TI  - C1 posterior arch crossing screw fixation for atlantoaxial joint instability.
AB  - STUDY DESIGN: Anatomical measurements and in vitro biomechanical testing were
      performed to evaluate a new method for posterior C1 fixation. OBJECTIVE: This
      study sought to assess C1 posterior arch crossing screw fixation for posterior C1
      C2 fixation, using anatomical measurements and biomechanical testing with
      traditional C1 pedicle screws (PS) in a cadaveric model. SUMMARY OF BACKGROUND
      DATA: Atlantoaxial instability often requires surgery, and the current methods
      for atlas fixation incur some risk to the vascular and neurological tissues.
      Thus, new, effective, and safe methods are needed for salvage operations.
      METHODS: Morphometric analysis of the C1 posterior arch was performed using 3
      dimensional computed tomography. Six fresh ligamentous human cervical spines (C0
      C4) were evaluated for their biomechanics. The specimens were tested in their
      intact condition and after stabilization (C1-C2 PS, C1 posterior arch screws
      [PAS] with C2 PS) and injury due to 1.5 N.m of pure moment in flexion, extension,
      lateral bending, and axial rotation. During testing, 3-dimensional angular motion
      was measured with a motion capture platform (Vicon Nexus). Data for all scenarios
      were recorded, and statistical analysis was performed. RESULTS: Anatomical
      assessment indicated that 91.51% of C1 posterior tubercles exceeded 7 mm in
      thickness, 93.40% had a width of the posterior arch of greater than 3.5 mm, and
      65.57% had a unilateral screw length of greater than 15 mm, indicating that the
      posterior arch fixation could be achieved by two 3.5 * 15-mm screws placed in a
      crossed manner. Twenty-two cases (11%) were not suitable for crossing screw
      placement because the posterior arch was flat and the entry point was present on
      the same side. Biomechanical testing showed that the PS and PAS rod-screw systems
      significantly reduced flexibility in flexion, extension, and rotation compared
      with the intact position. For lateral bending, there was a trend for the C1 PS
      and PAS systems toward decreased flexibility in comparison with the intact
      position. At the same time, C1 PAS decreased C1-C2 movement by 33.0% in left
      bending (P = 0.171) and 24.4% in right bending (P = 0.095); however, no
      significant difference was observed for left bending with C1 PAS compared with C1
      PS, and the C1 PS and PAS systems significantly reduced the flexibility more than
      destabilization. CONCLUSION: Crossing screw fixation of the C1 posterior arch is
      straightforward and imposes little risk of injury to the neural and vascular
      structures as long as the implants remain intraosseous. According to the results
      of our anatomical and biomechanical study, C1 posterior arch crossing screw
      fixation may constitute an alternative method for posterior atlantoaxial
      fixation. LEVEL OF EVIDENCE: 3.

PMID- 23873240
TI  - Surgical site infections in spine surgery: identification of microbiologic and
      surgical characteristics in 239 cases.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: The objective of this study was
      to describe the microbiology of surgical site infection (SSI) in spine surgery
      and relationship with surgical management characteristics. SUMMARY OF BACKGROUND
      DATA: SSI is an important complication of spine surgery that results in
      significant morbidity. A comprehensive and contemporary understanding of the
      microbiology of postoperative spine infections is valuable to direct empiric
      antimicrobial treatment and prophylaxis and other infection prevention
      strategies. METHODS: All cases of spinal surgery associated with SSI between July
      2005 and November 2010 were identified by the hospital infection control
      surveillance program using Centers for Disease Control National Health Safety
      Network criteria. Surgical characteristics and microbiologic data for each case
      were gathered by direct medical record review. RESULTS: Of 7529 operative spine
      cases performed between July 2005 and November 2010, 239 cases of SSI were
      identified. The most commonly isolated pathogen was Staphylococcus aureus
      (45.2%), followed by Staphylococcus epidermidis (31.4%). Methicillin-resistant
      organisms accounted for 34.3% of all SSIs and were more common in revision than
      in primary surgical procedures (47.4% vs. 28.0%, P = 0.003). Gram-negative
      organisms were identified in 30.5% of the cases. Spine surgical procedures
      involving the sacrum were significantly associated with gram-negative organisms
      (P < 0.001) and polymicrobial infections (P = 0.020). Infections due to gram
      negative organisms (P = 0.002) and Enterococcus spp. (P = 0.038) were less common
      in surgical procedures involving the cervical spine. Cefazolin-resistant gram
      negative organisms accounted for 61.6% of all gram-negative infections and 18.8%
      of all SSIs. CONCLUSION: Although gram-positive organisms predominated, gram
      negative organisms accounted for a sizeable portion of SSI, particularly among
      lower lumbar and sacral spine surgical procedures. Nearly half of infections in
      revision surgery were due to a methicillin-resistant organism. These findings may
      help guide choice of empiric antibiotics while awaiting culture data and
      antimicrobial prophylaxis strategies in specific spine surgical procedures. LEVEL
      OF EVIDENCE: 3.

PMID- 23873241
TI  - Unplanned return to the operating room in patients with adolescent idiopathic
      scoliosis: are we doing better with pedicle screws?
AB  - STUDY DESIGN: Prospective, longitudinal cohort. OBJECTIVE: To evaluate the
      incidence, timing, and risk factors for reoperation in patients with adolescent
      idiopathic scoliosis (AIS) treated with pedicle screws (PSs) compared with hybrid
      (Hb) constructs. SUMMARY OF BACKGROUND DATA: Rates of return to the operating
      room (OR) after definitive fusion for AIS vary, with a paucity of data on PS
      constructs. METHODS: A prospective multicenter database was retrospectively
      queried to identify consecutive patients with AIS who underwent posterior spinal
      fusion with either PS or Hb constructs with a minimum 2-year follow-up. All
      reoperations were stratified into an early group (<60 d) or a late group (>60 d).
      Univariate and multivariate logistical analyses were performed to identify
      potential risk factors related to reoperation. RESULTS: A total of 627 patients
      met the inclusion criteria (PS = 540, Hb = 87). There was a statistically
      significant difference in the rate of reoperations between the PS (3.5%) and Hb
      groups (12.6%), P < 0.001. Early return to the OR occurred in 2.0% of the
      patients with PS compared with 3.4% in the Hb group, P = 0.43. Late returns to
      the OR occurred in 1.5% of PS group versus 9.2% of the Hb group, P < 0.001.
      Multivariate analysis revealed longer operating time as an independent risk
      factor for an unplanned return to the OR in patients treated with PSs (P < 0.05).
      CONCLUSION: Our results suggest that patients with AIS treated with PS have
      decreased rates of unplanned return to the OR when compared with patients with Hb
      constructs. The majority of returns to the OR were early (<60 d) for the PS group
      compared with late (>60 d) for the Hb group. Longer operative times increased the
      risk of unplanned reoperation for the PS group. LEVEL OF EVIDENCE: 3.

PMID- 23873242
TI  - Substance P stimulates production of inflammatory cytokines in human disc cells.
AB  - STUDY DESIGN: Laboratory study. OBJECTIVE: The aims of this study were as
      follows: (1) to confirm that Substance P (SP) is expressed by nucleus pulposus
      (NP) and annulus fibrosus (AF) cells; (2) to determine the effect of SP on
      expression of inflammatory mediators in human disc cells and the effect of
      inflammatory mediators on the expression of SP; and (3) to characterize the
      relative expression of SP receptor isoforms in disc tissue and describe whether
      exposure to SP changes receptor expression. SUMMARY OF BACKGROUND DATA: SP,
      classically described as a neurotransmitter, acts as an inflammatory regulator in
      other tissue types, but its role within the intervertebral disc has not been
      characterized. METHODS: Human AF and NP cells from 7 individuals were expanded in
      monolayer and maintained in alginate bead culture. Cells were treated with SP or
      interleukin (IL)-1beta/tumor necrosis factor-alpha (TNF-alpha). After treatment,
      the cells were recovered and then RNA was isolated and transcribed into cDNA.
      Quantitative reverse-transcriptase polymerase chain reaction was performed to
      evaluate expression of inflammatory mediators and SP and its receptors. RESULTS:
      Disc cells treated with SP demonstrated significant upregulation of IL-1beta, IL
      6, and IL-8 in NP and AF cells whereas significant upregulation of RANTES and TNF
      occurred only in the AF cells. AF and NP cells expressed SP at low levels;
      expression did not change significantly with SP treatment but was significantly
      upregulated after treatment with IL-1beta/TNF-alpha. Both SP receptor isoforms
      were expressed by NP and AF cells. CONCLUSION: SP upregulates inflammatory
      mediators in disc cells. SP and its receptors were expressed in both NP and AF
      cells, and expression did not change after treatment with SP but increased after
      treatment with IL-1beta/TNF-alpha. SP likely acts in an autocrine or paracrine
      manner in intervertebral disc cells and may be involved in "crosstalk" between
      disc cells and neurons, providing a potential mechanism for transmission of
      painful discogenic stimuli.

PMID- 23873243
TI  - Symptomatic vertebral artery stenosis secondary to cervical spondylolisthesis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To present a rare case of vertebrobasilar
      insufficiency (VBI) syndrome secondary to the C6 level isthmic spondylolisthesis.
      SUMMARY OF BACKGROUND DATA: VBI associated with voluntary head movements is known
      as the bow hunter syndrome. It may manifest in temporary symptoms of dizziness,
      syncope, nausea, or motor and sensory deficits in certain head positions. The
      present syndrome is rare and difficult to diagnose. The authors describe a VBI
      case caused by vertebral artery compression due to the C6 level isthmic
      spondylolisthesis (to date, the authors have not found any other similar case
      described in the literature). METHODS: The patient was a 27-year-old male with a
      12-month history of vertigo and dizziness in relation to head movements. These
      problems interfered with his day-to-day activities.With other causes of
      neurological and cardiac origin dismissed, the patient was sent for an orthopedic
      evaluation.Radiological imaging showed spondylolisys, spondylolisthesis, and
      spina bifida between the facets of the C6 and C7. Dynamic radiographies evidenced
      C6 and C7 cervical instability.Angio-MRI indicated an anomalous trajectory of the
      right vertebral artery at the C6 level upon entering the foramen transversarium.
      However, there were no signs of stenosis. Dynamic angiography confirmed partial
      stenosis of the right vertebral artery upon rightward head rotation. The
      substantial suspicion of positional VBI after rejecting other diagnoses and the
      significant disability of the patient led to treating the patient with anterior
      cervical arthrodesis at the C6-C7 level. RESULTS: The patient was symptom free
      for more than 15 months' monitoring and returned to all his daily work and life
      activities. CONCLUSION: Isthmic spondylolisthesis must be considered as a cause
      within VBI. Surgery presents good results.

PMID- 23873244
TI  - Adult degenerative scoliosis treated with XLIF: clinical and radiographical
      results of a prospective multicenter study with 24-month follow-up.
AB  - STUDY DESIGN: Prospective, multicenter, single-arm study. OBJECTIVE: The
      objective of this study was to evaluate the clinical and radiographical results
      of patients undergoing extreme lateral interbody fusion (XLIF), a minimally
      disruptive lateral transpsoas retroperitoneal surgical approach for the treatment
      of degenerative scoliosis (DS). SUMMARY OF BACKGROUND DATA: Surgery for the
      treatment of DS has been reported to have acceptable results but is traditionally
      associated with high morbidity and complication rates. A minimally disruptive
      lateral transpsoas retroperitoneal surgical approach (XLIF) has become popular
      for the treatment of DS. This is the first prospective, multicenter study to
      quantify outcomes after XLIF in this patient population. METHODS: A total of 107
      patients with DS who underwent the XLIF procedure with or without supplemental
      posterior fixation at one or more intervertebral levels were enrolled in this
      study. Clinical and radiographical results were evaluated up to 24 months after
      surgery. RESULTS: Mean patient age was 68 years; 73% of patients were female. A
      mean of 3.0 (range, 1-6) levels were treated with XLIF per patient. Overall
      complication rate was low compared with traditional surgical treatment of DS.
      Significant improvement was seen in all clinical outcome measures at 24 months:
      Oswestry Disability Index, visual analogue scale for back pain and leg pain, and
      36-Item Short Form Health Survey mental and physical component summaries (P <
      0.001). Eighty-five percent of patients were satisfied with their outcome and
      would undergo the procedure again. In patients with hypolordosis, lumbar lordosis
      was corrected from a mean of 27.7 degrees  to 33.6 degrees  at 24 months (P <
      0.001). Overall Cobb angle was corrected from 20.9 degrees  to 15.2 degrees ,
      with the greatest correction observed in patients supplemented with bilateral
      pedicle screws. CONCLUSION: This study demonstrates the use of the XLIF procedure
      in the treatment of DS. XLIF is associated with good clinical and radiographical
      outcomes, with a substantially lower complication rate than has been reported
      with traditional surgical procedures. LEVEL OF EVIDENCE: 3.

PMID- 23873245
TI  - Low-molecular-weight heparin prophylaxis 24 to 36 hours after degenerative spine
      surgery: risk of hemorrhage and venous thromboembolism.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To assess the safety and efficacy
      of prophylactic low-molecular-weight heparin (LMWH) started 24 to 36 hours after
      degenerative spine surgery. SUMMARY OF BACKGROUND DATA: Venous thromboembolism
      (VTE) is a significant postoperative complication best averted with dual
      mechanical/pharmacological prophylaxis. Pharmacological prophylaxis is widely
      used in patients with spinal cord injury, but there is no consensus on its role
      in degenerative spine surgery, particularly after laminectomy with the concurrent
      risk of epidural hematoma. The literature suggests a small but potentially
      devastating hemorrhage risk when LMWH is started within 24 hours of spine
      surgery. An intermediate strategy is delayed LMWH initiation to minimize
      hemorrhage risk and retain benefits of dual prophylaxis. METHODS: Operative
      reports of the senior author were retrospectively reviewed for all cases of
      cervical and lumbar laminectomy from 2007 to 2011. Single-level decompressions
      without fusion and all nondegenerative cases were excluded. Baseline and
      operative details were recorded. Mechanical prophylaxis was used throughout
      admission, and prophylactic LMWH was started postoperative day 1 at 10 PM. All
      cases of postoperative hemorrhage (epidural hematoma, superficial hematoma,
      persistent wound drainage), deep venous thrombosis, and pulmonary embolism were
      noted. RESULTS: A total of 367 patients underwent multilevel laminectomy or
      laminectomy and fusion for degenerative disease. VTE risk factors (age >60 yr,
      smoking, obesity) were common. No patients receiving LMWH 24 to 36 hours after
      surgery developed postoperative hemorrhage (95% confidence interval: 0-0.8%).
      Nearly half of the study population underwent lower extremity ultrasonography or
      chest computed tomography, and acute VTE was diagnosed in 14 patients (3.8%; 95%
      confidence interval: 2.1-6.3). CONCLUSION: LMWH prophylaxis seems to carry a very
      low hemorrhage risk when started 24 to 36 hours after spine surgery. Larger,
      prospective studies are needed to assess the safety of early delayed LMWH
      administration more definitively. Even with aggressive prophylaxis, patients
      undergoing fusion or multilevel laminectomy for degenerative disease are at
      significant risk for VTE.

PMID- 23873246
TI  - Acquisition of thin coronal sectional dataset of cadaveric liver.
AB  - PURPOSE: To obtain the thin coronal sectional anatomic dataset of the liver by
      using digital freezing milling technique. METHODS: The upper abdomen of one
      Chinese adult cadaver was selected as the specimen. After CT and MRI examinations
      verification of absent liver lesions, the specimen was embedded with gelatin in
      stand erect position and frozen under profound hypothermia, and the specimen was
      then serially sectioned from anterior to posterior layer by layer with digital
      milling machine in the freezing chamber. The sequential images were captured by
      means of a digital camera and the dataset was imported to imaging workstation.
      RESULTS: The thin serial section of the liver added up to 699 layers with each
      layer being 0.2 mm in thickness. The shape, location, structure, intrahepatic
      vessels and adjacent structures of the liver was displayed clearly on each layer
      of the coronal sectional slice. CT and MR images through the body were obtained
      at 1.0 and 3.0 mm intervals, respectively. CONCLUSION: The methodology reported
      here is an adaptation of the milling methods previously described, which is a new
      data acquisition method for sectional anatomy. The thin coronal sectional
      anatomic dataset of the liver obtained by this technique is of high precision and
      good quality.

PMID- 23873247
TI  - Bilateral bifid ureter with unilateral renal vasculature variations.
AB  - During routine dissection of 82-year-old female cadaver with no known unfavorable
      medical history, we observed bilateral bifid ureter and variation in arterial
      supply of left kidney only. Careful examination revealed that there were bifid
      ureters on both sides enclosed in single facial sheath. It was also observed that
      both the ureter have different pattern of origin. On the right side, both the
      ureters were seen to be emerging from the hilum, one below another and joined
      together at the brim of the lesser pelvis just before crossing the right external
      iliac artery. Right kidney was supplied by single renal artery lying anterior to
      both the ureters. On the left side one ureter emerged from the hilum while the
      second one exited the kidney from a prominent lobule present below the inferior
      pole.

PMID- 23873248
TI  - On the adsorption/reaction of acetone on pure and sulfate-modified zirconias.
AB  - In situ FTIR spectroscopy was employed to investigate some aspects of the ambient
      temperature (actually, IR-beam temperature) adsorption of acetone on various pure
      and sulfate-doped zirconia specimens. Acetone uptake yields, on all examined
      systems and to a variable extent, different types of specific molecular
      adsorption, depending on the kind/population of available surface sites:
      relatively weak H-bonding interaction(s) with surface hydroxyls, medium-strong
      coordinative interaction with Lewis acidic sites, and strong H-bonding
      interaction with Bronsted acidic centres. Moreover acetone, readily and
      abundantly adsorbed in molecular form, is able to undergo the aldol condensation
      reaction (yielding, as the main reaction product, adsorbed mesityl oxide) only if
      the adsorbing material possesses some specific surface features. The
      occurrence/non-occurrence of the acetone self-condensation reaction is discussed,
      and leads to conclusions concerning the sites that catalyze the condensation
      reaction that do not agree with either of two conflicting interpretations present
      in the literature of acetone uptake/reaction on, mainly, zeolitic systems. In
      particular, what turns out to be actually necessary for the acetone aldol
      condensation reaction to occur on the examined zirconia systems is the presence
      of coordinatively unsaturated O(2-) surface sites of basicity sufficient to lead
      to the extraction of a proton from one of the CH3 groups of adsorbed acetone. 

PMID- 23873249
TI  - Incremental His-to-coronary sinus maneuver: a nonlocal electrogram-based
      technique to assess complete cavotricuspid isthmus block during typical flutter
      ablation.
AB  - BACKGROUND: Achievement of complete cavotricuspid isthmus (CTI) conduction block
      reduces typical atrial flutter recurrences after ablation. The lack of increase
      in the His-to-coronary sinus ostium atrial interval during incremental pacing
      (IP) from the low lateral right atrium may distinguish slow conduction from
      complete CTI conduction block. METHODS AND RESULTS: Sixty-six consecutive
      patients (age, 65+/-13 years; 18% female) were prospectively included. A <10 ms
      increase in the His-to-coronary sinus ostium atrial timing during low lateral
      right atrium IP at cycle length of 600 ms through 300 ms was compared with the
      previously reported IP maneuver for the confirmation of complete CTI block. On
      the basis of the IP maneuver, complete CTI block (phase 2) was achieved in 59
      patients, in 13 of whom an intermediate phase of functional CTI block (phase 1)
      was observed. In the remaining 7 patients, the IP maneuver did not allow for
      assessment of complete CTI block because of the presence of inconclusive
      potentials in the CTI ablation line. As compared with the IP maneuver, the
      incremental His-to-coronary sinus ostium maneuver was consistent with functional
      CTI block during phase 1 in all cases and conclusive of complete CTI block in 98%
      of cases during phase 2. CONCLUSIONS: The incremental His-to-coronary sinus
      ostium maneuver is analogous to the IP maneuver in distinguishing complete CTI
      block from persistent CTI conduction. This maneuver may provide confirmation of
      CTI block in those patients in whom assessment of local electrogram-based
      criteria is not feasible because of inconclusive potentials in the CTI ablation
      line.

PMID- 23873250
TI  - Exposure to nitrofurantoin during the first trimester of pregnancy and the risk
      for major malformations.
AB  - Antibacterial drugs are among the most common medications used by pregnant women.
      While medical literature generally defines nitrofurantoin as an antibiotic that
      is safe for use during the first trimester of pregnancy, new concerns about a
      possible association between congenital malformations following exposure to
      nitrofurantoin during the first trimester of pregnancy have recently surfaced. To
      address these concerns, we conducted a large population-based retrospective
      cohort study to assess this possible association (including cases of medical
      terminations of pregnancy or stillbirth) and congenital malformations. A
      computerized database for medications dispensed to pregnant women in southern
      Israel was linked with records from the district hospital. Associations between
      exposure to nitrofurantoin during the first trimester and major malformations
      were assessed. Our research included a total of 105,492 pregnancies, 1,112 of
      which involved pregnancy terminations for medical reasons. A total of 1,329
      infants and abortuses had been exposed to nitrofurantoin during the first
      trimester of pregnancy. Exposure to nitrofurantoin was not associated with
      increased risk of major malformations in general (adjusted OR = 0.85, 95% CI 0.67
      1.08) or with specific malformations. First trimester exposure to nitrofurantoin
      was not associated with increased risk for total major congenital malformations
      or with specific malformations.

PMID- 23873251
TI  - Overexpressed transcription factor FOXM1 is a potential diagnostic and adverse
      prognostic factor in postoperational gastric cancer patients.
AB  - PURPOSE: In the present study, we intend to detect the expression of Forkhead box
      transcription (FOXM1) in gastric cancer tissues and cell lines, and analyze the
      correlation between FOXM1 expression and clinic-pathological features as well as
      their association with clinic outcomes in patients with resectable gastric
      cancers. METHODS: We examined the expression of FOXM1 in 103 cancer tissues from
      patients who underwent gastrectomy during Jan 2007 to Nov 2007 and 68 randomly
      selected para-cancer tissues by immunohistochemistry. The expression of FOXM1
      protein in the benign and malignant human gastric cell lines was simultaneously
      detected using Western blot analysis. Data on clinic-pathological features and
      relevant prognostic factors in these patients were then analyzed. RESULTS: FOXM1
      expression was absolutely higher in gastric cancer than para-cancer tissues (P <
      0.001) and normal gastric epithelium cell lines (P = 0.022). No significant
      association was found between FOXM1 expression and any clinic-pathological
      parameters (P > 0.1). FOXM1 amplification was showed to be independently
      associated with prognosis in gastric cancer patients (P = 0.001), and its
      affection is more significant in patients with tumor size larger than 5 cm (P =
      0.004), pT3-4 (P = 0.003) or pIII-IV (P = 0.001) as a result of stage-stratified
      analysis. CONCLUSIONS: Overexpressed FOXM1 is a potential diagnostic and poor
      prognostic biomarker in postoperational gastric cancer patients.

PMID- 23873252
TI  - Reference limit of thyrotropin (TSH) and free thyroxine (FT4) in thyroperoxidase
      positive and negative subjects: a population based study.
AB  - BACKGROUND: Current reference values for thyroid function tests are based on data
      from different ethnicities and geographical areas. The aim of the present study
      was to determine reference intervals for thyrotropin (TSH) and free T4 (FT4),
      based on the criteria of the National Academy of Clinical Biochemistry (NACB) in
      an Iranian population. MATERIAL AND METHODS: This study was conducted within the
      framework of Tehran Thyroid Study (TTS), an ongoing prospective cohort of 5704
      randomly selected individuals, age >= 20 yr. A total of 2199 individuals (43.3%
      male, 56.7% female), based on NACB criteria were included in this study.
      Reference limit analysis was performed for the negative thyroid peroxidase
      antibody (TPOAb) group. RESULTS: After applying all exclusion criteria except
      TPOAb positivity (10.5%), data of 2459 participants remained for analysis. Of
      these, 953 (43.3%) were males and 1246 (56.7%) were females; the mean +/- SD age
      was 43.53 +/- 14.16 yr. The mean +/- SD and median+IQR for TSH were 1.77 mU/l +/-
      1.24 and 1.46 (0.93-2.23) mU/l, respectively. The 2.5th and 97.5th percentiles
      TSH were 0.32 mU/l and 5.06 mU/l respectively. The mean +/- SD and median (IQR)
      for FT4 for all negative TPOAb subjects were 1.19 +/- 0.16 and 1.18 (1.08-1.31)
      ng/dl respectively. CONCLUSION: Reference ranges for thyroid function tests need
      to be derived from national databases. This study determined age and sex specific
      TSH and FT4 reference ranges in a Tehranian population, which could eventually
      enable clinicians to classify patients more appropriately.

PMID- 23873253
TI  - The effect of intravitreal bevacizumab injection as the initial treatment for
      Coats' disease.
AB  - BACKGROUND: In Coats' disease, the most recent development in the treatment has
      been the intravitreal injection of anti-VEGF agents. The purpose of this article
      was to evaluate the effect of intravitreal bevacizumab as the initial treatment
      for Coats' disease in children and adults. METHODS: The study included 14
      pediatric patients and five adult patients with Coats' disease. They were treated
      with intravitreal bevacizumab (1.25 mg/0.05 ml) as the initial treatment,
      combined with or without other treatments. The analyses included the evaluation
      of basic clinical conditions. RESULTS: In the pediatric group, after a mean of
      9.1 months of follow-up, the differences in visual acuity were significant for
      the comparisons between the baseline examination and the follow-up examinations
      carried out at weeks 6, 12, and 24 after the baseline (P = 0.006, P = 0.004, P =
      0.005 respectively). Vitreoretinal fibrosis was observed in three patients (n =
      3, 21.4 %), among whom two showed fibrosis before treatment. All of the pediatric
      patients showed a resolution of fluid and exudation, and regression of the
      telangiectasia. In the adult group, after a mean of 10.6 months of follow-up, the
      differences in visual acuity were not statistically significant (P > 0.05)
      between the baseline and follow-up examinations. Vitreoretinal fibrosis (n = 2,
      40 %) was observed in two patients who both showed fibrosis before treatment. All
      of the adult patients showed a resolution of fluid and exudation, and regression
      of the telangiectasia. The differences in the change of BCVA between children and
      adults were not significant (P > 0.05) during the follow-up examinations.
      CONCLUSION: The intravitreal injection of bevacizumab as the initial treatment is
      associated with a measurable gain in visual acuity in patients with Coats'
      disease. Resolution of the subretinal fluid and exudation, and regression of the
      telangiectasia were observed in both pediatric and adult patients. Vitreoretinal
      fibrosis may be one of the natural courses of Coats' disease, and it remains
      uncertain whether bevacizumab accelerates the fibrosis phenomenon.

PMID- 23873254
TI  - Paired responses to intravitreal bevacizumab in diabetic macular edema:
      predictors of response in the fellow eye.
AB  - BACKGROUND: Factors predictive for response of diabetic macular edema (DME) to
      intravitreal bevacizumab (IVB) remain unclear. In this study, we assess the
      predictability of DME response to IVB based on the response to IVB in a
      previously treated fellow eye and other known pre-injection factors in (DME).
      METHODS: Retrospective chart review was conducted on 28 patients (56 eyes) with
      bilateral DME who underwent bilateral IVB therapy. Responses in both eyes were
      measured by change in central subfield thickness (CSFT) via optic coherence
      tomography (OCT), and change in visual acuity. Age, lens status, and starting
      macular thickness were recorded. RESULTS: We found 21 % of the reduction in CSFT
      after IVB on OCT in the study eye may be explained by the percentage change in
      CSFT in the previously treated fellow eye [CI: 0.092-0.716; p-value = 0.0141].
      Also, the pre-injection CSFT predicts 14 % of the response to IVB in the same eye
      [R2 = 9.6 %, p-value = 0.018]. When combined in a multi-factorial model, 33 % of
      the change in CSFT following IVB may be explained by these two factors. Lens
      status, change in visual acuity, and age were not statistically significant
      predictors of response. CONCLUSIONS: In DME, the response to IVB in an eye is
      partially explained by the pre-injection retinal thickness in the same eye and by
      the response to IVB in the previously treated fellow eye. Lens status, change in
      visual acuity, and age were not statistically significant predictors of response
      in this study.

PMID- 23873255
TI  - Comparison of clear corneal incision injuries between torsional and conventional
      phacoemulsification.
AB  - PURPOSE: To compare thermal and mechanical clear corneal incision (CCI) injuries
      after conventional and torsional phacoemulsification. DESIGN: A prospective,
      randomized clinical study. METHODS: A total of 80 eyes were evaluated for the
      profile of the incision at 1 day and 3 months postoperatively. The wound
      architecture was recorded with anterior segment optical coherence tomography (AS
      OCT). The incisional thickness increased by thermal injury, Descemet's membrane
      detachment (DMD) caused by mechanical injury, the presence of endothelial gaping,
      loss of coaptation, and wound retraction of the conventional phaco group and the
      torsional phaco group were compared. RESULTS: The corneal thickness at the
      incision site of the torsional ultrasound group was significantly lower than the
      conventional group compared to at the first postoperative visit (1187.55 +/-
      75.66, 1233.62 +/- 85.87, P = .013). However, this thickness was similar between
      the two groups at 3 months postoperatively. The central endothelial cell loss was
      significantly lower in the torsional ultrasound group after 3 months (417 +/-
      143, 322 +/- 130, P = .003). There was a positive correlation between cumulated
      dissipated energy (CDE) and the incisional corneal thickness change that was
      observed by AS-OCT. Other OCT outcome parameters (such as endothelial gap, DMD,
      epithelial gap, and uncoaptation) that may be caused by mechanical injury did not
      differ significantly between the groups on postoperative day one or after 3
      months. CONCLUSIONS: The torsional ultrasound mode may provide a lower level of
      phacoemulsification time and energy and induce less incisional corneal thickness
      caused by thermal injury in the early postoperative period. The long-term wound
      healing appeared the same in both ultrasound mode groups.

PMID- 23873257
TI  - Hyperopic shift in refraction in adults with aging.

PMID- 23873256
TI  - The effect of age and cataract surgery on macular pigment optic density: a cross
      sectional, comparative study.
AB  - BACKGROUND: To analyze the effects of age, cataract surgery and postoperative
      period on macular pigment optical density (MPOD). METHODS: The study included
      cases referred to Ankara University Department of Ophthalmology, between April
      and June 2012, who had a transparent natural lens or had undergone cataract
      surgery at least a year ago with their best corrected visual acuity of >= 0.5
      based on Snellen chart. Presence of an ocular disease that might affect lens,
      retina and optic nerve (cataract, macular degeneration, diabetic retinopathy,
      glaucoma etc.), cataract surgery within the previous year, light-colored iris,
      smoking and use of micronutrition supplementation were determined as exclusion
      criteria. After detailed opthalmologic examination of all patients, they were
      divided into three groups based on their age and their lens status as: group 1,
      patients < 50 years of age having a clear lens; group 2, patients > 50 years of
      age having a clear lens; and group 3, patients > 50 years of age who had cataract
      surgery. Age, gender, and postoperative period of the patients as well as the
      MPOD values of the eyes measured with heterochromatic flicker photometric (HFP)
      method (MacularMetricsTM) were included in the analysis. RESULTS: Sixty-eight
      eyes of 37 cases with a mean age of 53.4 +/- 15.3 years were enrolled in the
      study. Group 1 included 20 eyes of 10 cases (mean age 29.4 +/- 9.5); group 2
      included 32 eyes of 16 cases (mean age 60.3 +/- 6.8); and group 3 included 16
      eyes of 11 cases (mean age 65.2 +/- 9.7). The mean macular pigment optical
      density value of all cases was 0.511 +/- 0.192 log unit, while the mean MPOD
      values of groups 1, 2 and 3 were 0.570 +/- 170, 0.528 +/- 203 and 0.400 +/- 180
      log units, respectively. The mean MPOD values of the patients with clear lens
      aged < 50 and aged > 50 years did not reveal a statisticially significant
      difference (p = 1). However, the mean MPOD value of the cataract surgery group
      (group 3) was found to be statistically significantly lower than the group 1 and
      group 2 (p = 0.022, p = 0.039, respectively). The correlations between MPOD
      values and postoperative periods of the patients in group 3 showed that a
      decrease in MPOD values in parallel with duration of the postoperative period and
      this negative correlation was found to be statistically significant (r: -0.66, p
      = 0.005). CONCLUSION: Our study has demonstrated that a significant correlation
      does not exist between age of the patients and MPOD values. MPOD values were
      lower than age-matched patients who had undergone cataract surgery and finally an
      inverse correlation existed between duration of the postoperative period after
      cataract surgery and MPOD values.

PMID- 23873258
TI  - Early recognition of septic shock in children.
AB  - In the developed countries septic shock has a favorable outcome for the majority
      of previously healthy children but also in children with comorbidities if all
      available medical resources were used. However, septic shock remains a rare
      disease in children, and caregivers might not always recognize it at early
      stages. The resulting delay of appropriate treatment prevents lower mortality
      rates. The current review gives an overview of the pathophysiology of septic
      shock and the early clinical signs as well as new and future diagnostic
      approaches such as "point-of-care" laboratory tests for an early diagnosis. 

PMID- 23873259
TI  - Study of the synthesis, antiproliferative properties, and interaction with DNA
      and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic
      polyaromatic amines.
AB  - The chemical and biological features of two newly synthesized [PtCl2(L)(2
      aminonaphthalene)] complexes (L is NH3 or 2-aminonaphthalene) were compared with
      those of two already reported enantiomeric complexes of formula [PtCl2(DABN)]
      [DABN is (R)-1,1'-binaphthyl-2,2'-diamine or (S)-1,1'-binaphthyl-2,2'-diamine].
      Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal
      (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in
      vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the
      cytotoxicity of [PtCl2(NH3)(2-aminonaphthalene)] was better than that of
      cisplatin for all cell lines, and rather resembled that of oxaliplatin. The
      solution behavior of the whole series of complexes and the absence of an evident
      relationship between lipophilicity and cytotoxicity seem to suggest that all
      these experimental parameters are probably smoothed out during the 3-day
      cytotoxicity experiments and do not strongly affect the half-maximal inhibitory
      concentrations. The results of electrophoretic studies indicate that different
      kinds of interaction with DNA can be involved in the mode of action of these
      complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex
      DNA being strongly implicated in particular for [PtCl2(NH3)(2-aminonaphthalene)].

PMID- 23873260
TI  - A gender discrepancy analysis of heterosexual sexual behaviors in two university
      samples.
AB  - The current study aimed to (1) offer a large-scale enumeration of college
      students' lifetime sexual behaviors and sexual behaviors at last event, and (2)
      apply a gender discrepancy lens to college students' sexual behaviors in order to
      examine potential gender differences in heterosexual college students'
      experiences. Nine-hundred and seventy college students between the ages of 18 and
      27 from two large universities in the United States participated in the current
      study. Participants filled out a paper-pencil questionnaire during the last 30
      min of class. Measures of lifetime sexual behaviors and engagement in behaviors
      at last sexual event were replicated from the National Survey of Sexual Health
      Behavior. Most college students engaged in some form of sexual behavior (manual,
      oral, vaginal-penile, anal). Men more frequently reported engaging in receptive
      sexual behaviors (e.g., receiving oral sex) where as women were more likely to
      engage in performative sexual behaviors (e.g., performing oral sex). At most
      recent sexual event, men were more likely than women to report being the sexual
      initiator. Findings highlight gender differences in sexual behavior and provide a
      foundation for social norms interventions. Holistic sexual health promotion for
      young adults includes acknowledging and discouraging sites of disparity in equity
      and pleasure. Therefore, college-level sexual health educators should pay
      attention to the potential pleasure gap between men and women in heterosexual
      encounters, and to see pleasure as an important part of sexual health that should
      be included in social norms campaigns.

PMID- 23873261
TI  - Changes in cancer incidence attributable to tobacco smoking in Germany, 1999
      2008.
AB  - Tobacco smoking, a major cancer risk factor, is very common in Germany as in many
      other high-income countries. Few studies have assessed the burden of tobacco
      associated cancer incidence in the German population. We calculated the
      proportion of cancers attributable to tobacco smoking to estimate the burden of
      tobacco-associated cancer in 1999 and 2008. Smoking prevalence was determined
      from national surveys of a representative sample of the German population in 1998
      and 2008-2011, and data on relative risks were obtained from meta-analyses.
      Cancer incidence for the years 1999 and 2008 was estimated by the German Centre
      for Cancer Registry Data at the Robert Koch Institute. We estimate that 72,208
      incident cancer cases were attributable to tobacco smoking in Germany in 2008, an
      increase of >6,200 cases over 1999 levels. Among the cases in 2008 were 55,057
      cases among men (22.8% (95% CI, 21.3-24.1) of all new cases) and 17,151 cases
      among women (7.9% (95% CI, 7.21-8.68) of all new cases). The highest proportions
      attributable to smoking were estimated for cancer of the lung, larynx, pharynx
      and the lower urinary tract. Tobacco smoking is currently responsible for more
      than one in five cancer cases among men and nearly 1 in 12 among women.
      Considering the increasing trends in cancer incidence and, until very recently,
      rising prevalence of smoking among women, it can be expected that the number of
      tobacco-attributable cancer cases will rise further. 

PMID- 23873262
TI  - Dipyreno- and diperyleno-anthracenes from glyoxylic Perkin reactions.
AB  - Twofold Perkin condensation of 2,5-dibromophenylene-1,4-diacetic acid with
      arylglyoxylic acids followed by cyclo-dehydrobromination leads to dipyreno- and
      diperyleno-anthracene tetraesters and diimides. The imides show surprisingly
      large absorption shifts versus the esters, illustrating that electron-withdrawing
      substituents at the anthracene unit efficiently impart long wavelength absorption
      in such electron-deficient graphene nanoribbon fragments. 

PMID- 23873263
TI  - The impact of health insurance programs on out-of-pocket expenditures in
      Indonesia: an increase or a decrease?
AB  - We used panel data from the Indonesian Family Life Survey to investigate the
      impact of health insurance programs on reducing out-of-pocket expenditures. We
      employed three linear panel data models, two of which accounted for endogeneity:
      pooled ordinary least squares (OLS), pooled two-stage least squares (2SLS) for
      instrumental variable (IV), and fixed effects (FE). The study revealed that two
      health insurance programs had a significantly negative impact on out-of-pocket
      expenditures by using IV estimates. In the IV model, Askeskin decreased out-of
      pocket expenditures by 34% and Askes by 55% compared with non-Askeskin and non
      Askes, respectively, while Jamsostek was found to bear a nonsignificant effect on
      out-of-pocket expenditures. In the FE model, only Askeskin had a significant
      negative effect with an 11% reduction on out-of-pocket expenditures. This study
      showed that two large existing health insurance programs in Indonesia, Askeskin
      and Askes, effectively reduced household out-of-pocket expenditures. The ability
      of programs to offer financial protection by reducing out-of-pocket expenditures
      is likely to be a direct function of their benefits package and co-payment
      policies. 

PMID- 23873266
TI  - Thermodynamic parameters for Eu(III) binding to Datura innoxia root material.
AB  - Plants offer the potential for selective removal and sequestration of toxic heavy
      metals from contaminated soil. Phytoextraction of metal ions involve their
      transport through the plant's root system and into its shoots and leaves. This
      study investigates the thermodynamics of Eu(III) ion chemical interactions with
      Datura innoxia plant root materials under solution conditions of pH 4.0 and 5.0.
      Both changes in enthalpies (?H) and entropies (?S) of metal binding were
      elucidated from isotherms collected under varied temperature conditions using
      regularized regression data analysis and conditional affinity spectra. ?H values
      for binding to root materials at pH 4.0 and 5.0 were each calculated to be +30
      kJ/mol. Values of DeltaS for these same materials were found to be +170 and +153
      J/mol K for solution conditions of pH 4.0 and 5.0, respectively. These results
      suggest binding to the root material to be entropically driven (?S degrees  > 0
      and DeltaH > 0) through possible displacement of waters of solvation.

PMID- 23873265
TI  - The p53-PUMA axis suppresses iPSC generation.
AB  - Mechanisms underlying the reprogramming process of induced pluripotent stem cells
      remain poorly defined. Like tumorigenesis, generation of induced pluripotent stem
      cells was shown to be suppressed by the Trp53 (p53) pathway, at least in part via
      p21Cdkn1a (p21)-mediated cell cycle arrest. Here we examine the role of PUMA, a
      pro-apoptotic mediator of p53, during somatic reprogramming in comparison to p21
      in the p53 pathway. Using mouse strains deficient in these molecules, we
      demonstrate that PUMA is an independent mediator of the negative effect of p53 on
      induced pluripotent stem cell induction. PUMA deficiency leads to a better
      survival rate associated with reduced DNA damage and fewer chromosomal
      aberrations in induced pluripotent stem cells, whereas loss of p21 or p53 results
      in an opposite outcome. Given these new findings, PUMA may serve as a distinct
      and more desirable target in the p53 pathway for induced pluripotent stem cell
      generation, thereby having important implications for potential therapeutic
      applications of induced pluripotent stem cells.

PMID- 23873267
TI  - Triamcinolone and ritonavir leading to drug-induced Cushing syndrome and adrenal
      suppression: description of a new case and review of the literature.
AB  - The protease inhibitor (PI) ritonavir is a potent inhibitor of cytochrome P450
      (CYP) 3A4 activity and frequently prescribed to boost the effectiveness of other
      PIs as part of highly active antiretroviral therapy. It is well established that
      ritonavir is capable of inducing iatrogenic Cushing syndrome (ICS) through a drug
      drug interaction with inhaled fluticasone that leads to the inhibition of CYP3A
      activity. A rapidly increasing number of case reports are being published
      describing ICS induced by the interaction of ritonavir and injected
      corticosteroids, namely triamcinolone acetonide. A review of the current
      literature identified 15 cases (including the one reported here) of ICS and
      suppression of the hypothalamic-pituitary-adrenal axis after periradicular
      injection of triamcinolone acetonide. Considering an aging human immunodeficiency
      virus (HIV)-infected population an increasing number of patients will present
      with degenerative musculoskeletal disease and be seeking pain relief. Based on
      data reported in the literature and our own experience triamcinolone injections
      during ritonavir-based therapy should be avoided. After failure of all
      conservative therapeutic options methylprednisolone may represent a therapeutic
      alternative for steroid injections in HIV patients receiving PI-based antiviral
      therapy since it has to date not been associated with ICS. 

PMID- 23873268
TI  - Molecular basis for differential elongation of omega-3 docosapentaenoic acid by
      the rat Elovl5 and Elovl2.
AB  - Functional characterization of the rat elongases, Elovl5 and Elovl2, has
      identified that Elovl2 is crucial for omega-3 docosahexaenoic acid (DHA) (22:6n
      3) synthesis. While the substrate specificities of the rat elongases had some
      overlap, only Elovl2 can convert the C22 omega-3 PUFA docosapentaenoic acid (DPA)
      (22:5n-3) to 24:5n-3, which is the penultimate precursor of DHA. In order to
      better understand the potential for these elongases to be involved in DHA
      synthesis, we have examined the molecular reasons for the differences between
      Elovl5 and Elovl2 in their ability to elongate DPA to 24:5n-3. We identified a
      region of heterogeneity between Elovl5 and Elovl2 spanning transmembrane domains
      6 and 7. Using a yeast expression system, we examined a series of Elovl2/Elovl5
      chimeras and point mutations to identify Elovl2 residues within this region which
      are responsible for DPA substrate specificity. The results indicate that the
      cysteine at position 217 in Elovl2 and a tryptophan at the equivalent position in
      Elovl5 explain their differing abilities to elongate DPA to 24:5n-3. Further
      studies confirmed that Elovl2 C217 is a critical residue for elongation of DPA at
      the level observed in the native protein. Understanding the ability of elongases
      to synthesize 24:5n-3 may provide a basis for using sequence data to predict
      their ability to ultimately support DHA synthesis. 

PMID- 23873270
TI  - Effect of alkyl chain length and anion species on the interfacial nanostructure
      of ionic liquids at the Au(111)-ionic liquid interface as a function of
      potential.
AB  - Colloid probe atomic force microscopy (AFM) force measurements are used to
      elucidate the effect of variation in the cation alkyl chain length and the anion
      species on IL nanostructure at Au(111) surfaces as a function of potential. Four
      ionic liquids (ILs) are examined: 1-ethyl-3-methylimidazolium
      tris(pentafluoroethyl)trifluorophosphate ([EMIM] FAP), 1-butyl-3
      methylimidazolium tris(pentafluoroethyl)trifluorophosphate ([BMIM] FAP), 1-hexyl
      3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate ([HMIM] FAP) and 1
      butyl-3-methylimidazolium iodide ([BMIM] I). The step-wise force-distance
      profiles show the ILs adopt a multilayered morphology, with stronger near surface
      structure present at more biased potentials. The results suggest that the
      innermost (interfacial) layer is enriched in counter ions strongly bound to the
      Au(111) surface. For ILs with FAP(-) anions, the cations in the interfacial layer
      at negative potentials pack more neatly than the anions at positive potentials,
      and thus more effectively template structure in subsequent layers. [BMIM] FAP has
      the weakest interfacial structure. [EMIM] FAP has stronger interfacial structure
      because the imidazolium rings of [EMIM](+) cations in the interfacial layer are
      orientated towards the Au(111) surface, and this more parallel orientation is
      favourable for templating structure. [HMIM] FAP is more strongly structured than
      [BMIM] FAP because the longer cation alkyl chain increases solvophobic
      interactions which lead to better defined near surface structure. The response of
      [BMIM] I to changes in potential is opposite to that of the FAP(-) ILs. [BMIM] I
      interfacial nanostructure is stronger at positive potentials, because I(-) anions
      pack more neatly at the Au(111) surface than [BMIM](+) cations, which templates
      stronger structure in subsequent layers. 

PMID- 23873271
TI  - The effect of the 4-amino functionality on the photophysical and DNA binding
      properties of alkyl-pyridinium derived 1,8-naphthalimides.
AB  - The synthesis and characterisation of two cationic pyridinium based 4-amino-1,8
      naphthalimide derivatives (2 and 3) are described and compared to those of
      compound 1. The photophysical properties of 2 and 3 are shown to vary greatly
      with the solvent polarity and H-bonding ability. The dimethylamino substitution
      in 3 results in a weak quantum yield of fluorescence emission due to faster non
      radiative deactivation of the excited singlet state than that seen for 2. As with
      1, the fluorescence of 2 was found to be enhanced in its 1 : 1 complex with 5'
      adenosine-monophosphate (5'-AMP) while it was partially quenched in its complex
      with 5'-guanosine-monophosphate (5'-GMP). In contrast, the fluorescence of 3 was
      enhanced ('switched on') in the presence of both adenine and guanine rich
      sequences. Linear and circular dichroism studies showed that each of 1, 2 and 3
      binds to double-stranded DNA by intercalation. However, 2 and 3 do not show the
      preference for AT-rich DNA observed for 1. Comparative fluorescence studies with
      double stranded DNA show that the emission of was 16 times enhanced in its DNA
      bound form, suggesting potential use of this structure as a spectroscopic probe
      for studying nucleic acid structure.

PMID- 23873269
TI  - High density lipoproteins and endothelial functions: mechanistic insights and
      alterations in cardiovascular disease.
AB  - Prospective population studies in the primary prevention setting have shown that
      reduced plasma levels of HDL cholesterol are associated with an increased risk of
      coronary disease and myocardial infarction. Experimental and translational
      studies have further revealed several potential anti-atherogenic effects of HDL,
      including protective effects on endothelial cell functions. HDL has been
      suggested to protect endothelial cell functions by prevention of oxidation of LDL
      and its adverse endothelial effects. Moreover, HDL from healthy subjects can
      directly stimulate endothelial cell production of nitric oxide and anti
      inflammatory, anti-apoptotic, and anti-thrombotic effects as well as endothelial
      repair processes. However, several recent clinical trials using HDL cholesterol
      raising agents, such as torcetrapib, dalcetrapib, and niacin, did not demonstrate
      a significant reduction of cardiovascular events in patients with coronary
      disease. Of note, growing evidence suggests that the vascular effects of HDL can
      be highly heterogeneous and vasoprotective properties of HDL are altered in
      patients with coronary disease. Characterization of underlying mechanisms and
      understanding of the clinical relevance of this "HDL dysfunction" is currently an
      active field of cardiovascular research. Notably, in some recent studies no clear
      association of higher HDL cholesterol levels with a reduced risk of
      cardiovascular events was observed in patients with already established coronary
      disease. A greater understanding of mechanisms of action of HDL and its altered
      vascular effects is therefore critical within the context of HDL-targeted
      therapies. In this review, we will address different effects of HDL on
      endothelial cell functions potentially relevant to atherosclerotic vascular
      disease and explore molecular mechanisms leading to "dysfunctional HDL". 

PMID- 23873272
TI  - Met, IGF1R, and other new targets in upper GI malignancies.
AB  - OPINION STATEMENT: Upper gastrointestinal (GI) malignancies comprise some of the
      most aggressive human cancers. Expanding knowledge of molecular mechanisms is
      finally translating into clinical application, and this has occurred at a
      relatively rapid rate in the past several years. However, despite recent advances
      in targeted therapies in upper GI cancers our overall success with targeted
      therapeutics in this disease area remains dismal. This statement is particularly
      troubling given some sobering facts: upper GI malignancies are prevalent as well
      as aggressive with a high morbidity and mortality. Esophagus and gastric cancer
      combined have an annual global incidence of over 1.2 million new cases annually
      while median survival is less than 1 year for most patients with metastatic
      disease. Progress has been limited due to several factors including: disease
      heterogeneity and variance of phenotype across the globe, clinical trial design
      strategies that have not yet incorporated selective mechanisms to afford
      individualized matching of drug to tumor molecular profile and last, a lack of
      validated predictive markers. Nevertheless there is evidence that many targeted
      agents can be administered safely at doses that achieve the required effect at
      the protein level. Several drugs that have negative early trial results can be
      potentially vital therapeutic agents if patient selection is appropriate.

PMID- 23873273
TI  - ICU-acquired pneumonia with or without etiologic diagnosis: a comparison of
      outcomes.
AB  - OBJECTIVES: The impact of ICU-acquired pneumonia without etiologic diagnosis on
      patients' outcomes is largely unknown. We compared the clinical characteristics,
      inflammatory response, and outcomes between patients with and without
      microbiologically confirmed ICU-acquired pneumonia. DESIGN: Prospective
      observational study. SETTING: ICUs of a university teaching hospital. PATIENTS:
      We prospectively collected 270 consecutive patients with ICU-acquired pneumonia.
      Patients were clustered according to positive or negative microbiologic results.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the
      characteristics and outcomes between both groups. Negative microbiology was found
      in 82 patients (30%). Both groups had similar baseline severity scores. Patients
      with negative microbiology presented more frequently chronic renal failure (15
      [18%] vs 11 [6%]; p=0.003), chronic heart disorders (35 [43%] vs 55 [29%];
      p=0.044), less frequently previous intubation (44 [54%] vs 135 [72%]; p=0.006),
      more severe hypoxemia (PaO2/FIO2: 165+/-73 mm Hg vs 199+/-79 mm Hg; p=0.001), and
      shorter ICU stay before the onset of pneumonia (5+/-5 days vs 7+/-9 days;
      p=0.001) compared with patients with positive microbiology. The systemic
      inflammatory response was similar between both groups. Negative microbiology
      resulted in less changes of empiric treatment (33 [40%] vs 112 [60%]; p=0.005)
      and shorter total duration of antimicrobials (13+/-6 days vs 17+/-12 days;
      p=0.006) than positive microbiology. Following adjustment for potential
      confounders, patients with positive microbiology had higher hospital mortality
      (adjusted odds ratio 2.96, 95% confidence interval 1.24-7.04, p=0.014) and lower
      90-day survival (adjusted hazard ratio 0.50, 95% confidence interval 0.27-0.94,
      p=0.031), with a nonsignificant lower 28-day survival. CONCLUSIONS: Although the
      possible influence of previous intubation in mortality of both groups is not
      completely discarded, negative microbiologic findings in clinically suspected ICU
      acquired pneumonia are associated with less frequent previous intubation, shorter
      duration of antimicrobial treatment, and better survival. Future studies should
      corroborate the presence of pneumonia in patients with suspected ICU-acquired
      pneumonia and negative microbiology.

PMID- 23873274
TI  - Microvascular effects of heart rate control with esmolol in patients with septic
      shock: a pilot study.
AB  - OBJECTIVE: beta-blocker therapy may control heart rate and attenuate the
      deleterious effects of beta-stimulating catecholamines in septic shock. However,
      their negative chronotropy and inotropy may potentially lead to an
      inappropriately low cardiac output, with a subsequent compromise of microvascular
      blood flow. The purpose of the present pilot study was to investigate the effects
      of reducing heart rate to less than 95 beats per minute in patients with septic
      shock using the beta-1 adrenoceptor blocker, esmolol, with specific focus on
      systemic hemodynamics and the microcirculation. DESIGN: Prospective,
      observational clinical study. SETTING: Multidisciplinary ICU at a university
      hospital. MEASUREMENTS AND MAIN RESULTS: After 24 hours of initial hemodynamic
      optimization, 25 septic shock patients with a heart rate greater than or equal to
      95 beats per minute and requiring norepinephrine to maintain mean arterial
      pressure greater than or equal to 65 mm Hg received a titrated esmolol infusion
      to maintain heart rate less than 95 beats per minute. Sublingual microcirculatory
      blood flow was assessed by sidestream dark-field imaging. All measurements,
      including data from right heart catheterization and norepinephrine requirements,
      were obtained at baseline and 24 hours after esmolol administration. Heart rates
      targeted between 80 and 94 beats per minute were achieved in all patients.
      Whereas cardiac index decreased (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m;
      p<0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m;
      p=0.32). Microcirculatory blood flow in small vessels increased (2.8 [2.6; 3.0]
      vs 3.0 [3.0; 3.0]; p=0.002), while the heterogeneity index decreased (median 0.06
      [interquartile range 0; 0.21] vs 0 [0; 0]; p=0.002). PaO2 and pH increased while
      PaCO2 decreased (all p<0.05). Of note, norepinephrine requirements were
      significantly reduced by selective beta-1 blocker therapy (0.53 [0.29; 0.96] vs
      0.41 [0.22; 0.79] ug/kg/min; p=0.03). CONCLUSIONS: This pilot study demonstrated
      that heart rate control by a titrated esmolol infusion in septic shock patients
      was associated with maintenance of stroke volume, preserved microvascular blood
      flow, and a reduction in norepinephrine requirements.

PMID- 23873275
TI  - Impact of regular collaboration between infectious diseases and critical care
      practitioners on antimicrobial utilization and patient outcome.
AB  - OBJECTIVE: Antimicrobial stewardship programs have been shown to help reduce the
      use of unnecessary antimicrobial agents in the hospital setting. To date, there
      has been very little data focusing on high-use areas, such as the medical ICU. A
      prospective intervention was done to assess guideline compliance, antimicrobial
      expenditure, and healthcare cost when an infectious disease fellow interacts
      regularly with the medical ICU team. DESIGN: A 3-month retrospective chart review
      was followed by a 3-month prospective intervention the following year. Two
      hundred forty-six total charts were reviewed to assess generally accepted
      guideline compliance, demographics, and microbiologic results. SETTING: Twenty
      four-bed medical ICU at an 861-bed tertiary care, university teaching hospital in
      North Carolina. SUBJECTS: Patients receiving antibiotics in the medical ICU.
      INTERVENTION: During the intervention period, the infectious disease fellow
      reviewed the charts, including physician notes and microbiology data, and
      discussed antimicrobial use with the medical ICU team. MEASUREMENTS AND MAIN
      RESULTS: Antimicrobial use, treatment duration, Acute Physiology and Chronic
      Health Evaluation II scores, length of stay, mechanical ventilation days, and
      mortality rates were compared during the two periods. RESULTS: No baseline
      statistically significant differences in the two groups were noted (i.e., age,
      gender, race, or Acute Physiology and Chronic Healthcare Evaluation II scores).
      Indications for antibiotics included healthcare-associated (53%) and community
      acquired pneumonias (17%). Significant reductions were seen in extended-spectrum
      penicillins (p=0.0080), carbapenems (p=0.0013), vancomycin (p=0.0040), and
      metronidazole (p=0.0004) following the intervention. Antimicrobial modification
      led to an increase in narrow-spectrum penicillins (p=0.0322). The intervention
      group had a significantly lower rate of treatments that did not correspond to
      guidelines (p<0.0001). There was a reduction in mechanical ventilation days
      (p=0.0053), length of stay (p=0.0188), and hospital mortality (p=0.0367). The
      annual calculated healthcare savings was $89,944 in early antibiotic cessation
      alone. CONCLUSION: Active communication with an infectious disease practitioner
      can significantly reduce medical ICU antibiotic overuse by earlier modification
      or cessation of antibiotics without increasing mortality. This in turn can reduce
      healthcare costs, foster prodigious education, and strengthen relations between
      the subspecialties.

PMID- 23873276
TI  - [Sequential cochlear implantation in an adult with extremely asymmetric hearing
      experience].

PMID- 23873277
TI  - [Secondary laryngeal malignancy: a laryngeal tumor of unexpected origin].

PMID- 23873278
TI  - English publication rate of 3,205 abstracts presented at the Annual Meeting of
      the Japanese Orthopaedic Association and the Annual Research Meeting of the
      Japanese Orthopaedic Association.
AB  - BACKGROUND: Previous studies reported that the publication rate of abstracts
      presented at overseas meetings was around 50 %. The study objectives were to
      determine the rate of publication in English-language journals and the impact
      factor (IF) for all papers presented at the Annual Meeting of the Japanese
      Orthopaedic Association (JOA) and Annual Research Meeting of the Japanese
      Orthopaedic Association (JOAR), and to compare the publication rates and IFs from
      abstracts accepted for oral versus poster presentations. METHODS: Titles and
      first authors were identified for 1,676 abstracts of free papers accepted for
      presentation to the JOA in 2006 and 2007, and 1,529 abstracts to the JOAR from
      2006 to 2008. We identified the associated journal publications by searching
      PubMed, and IFs were determined using the journal citation reports. The
      publication rates and IFs for papers accepted for oral versus poster
      presentations were compared using statistical analysis. RESULTS: The overall
      publication rate was 25.5 % from the JOA and 50 % from the JOAR. There were no
      significant differences in yearly publication rates, or between oral and poster
      presentations for each year. The average IFs for all publications from the JOA
      was 2.45 and that from the JOAR was 3.5. There were no significant differences in
      yearly IFs, or between oral and poster presentations for each year (P > 0.05).
      CONCLUSIONS: The rate from JOAR was similar to publication rates for abstracts
      presented at overseas orthopedic meetings, however, the rate from JOA was half
      that of publication rates for abstracts presented at overseas orthopedic
      meetings, indicating that JOA may provide a below average contribution of new
      medical data to the international scientific community. No significant difference
      in publication rates between oral and poster presentations were found, and this
      suggests a need for improvement of the review system for the annual meeting and
      that review scores at the meetings did not predict the publication fate of
      abstracts.

PMID- 23873279
TI  - Microendoscopic discectomy in athletes.
AB  - BACKGROUND: Management of lumbar disc herniation in athletes is challenging
      because a prolonged period of postoperative rehabilitation prevents the athlete
      from participating in sporting activity, resulting in loss of competitive form.
      No study reporting the clinical results of microendoscopic discectomy (MED) in
      athletes was identified in a literature search through PubMed, in spite of the
      relatively long history of this treatment. The objective of this study was to
      evaluate the efficacy of MED for athletes, focusing on their ability to quickly
      resume their sports activity. METHODS: Twenty-five competitive athletes, who
      underwent MED participated in this study. The level of sporting activity patients
      were capable of achieving, and the time until complete return to competitive
      level were assessed. The Japanese Orthopaedic Association (JOA) score and short
      form 36 (SF-36) were also evaluated. RESULTS: Two patients did not return to
      sporting activity for reasons unrelated to the lumbar diseases. Among the
      remaining 23 cases, 19 (82.6 %) successfully returned to their original levels of
      sporting activity. One patient (4.4 %) could not return to his pre-injury level
      of sporting activity because of residual pain. He changed his field from a high
      school sports team to a low-level sports society. The mean period until complete
      return to competition was 10.8 weeks (range 5-16 weeks). Three patients (13.0 %)
      could not resume sporting activity because of residual pain. The mean improvement
      rate of JOA score at final follow-up was 80.4 %. Significant improvements in SF
      36 were observed in all subscales except in general health perceptions.
      CONCLUSIONS: MED is a well-balanced technique which offers a high probability of
      return and an early return to the same level of sporting activity, both of which
      are optimal aims in treatment of athletes with lumbar disc herniation.

PMID- 23873281
TI  - Forcing of anthropogenic aerosols on temperature trends of the sub-thermocline
      southern Indian Ocean.
AB  - In the late twentieth century, the sub-thermocline waters of the southern
      tropical and subtropical Indian Ocean experienced a sharp cooling. This cooling
      has been previously attributed to an anthropogenic aerosol-induced strengthening
      of the global ocean conveyor, which transfers heat from the subtropical gyre
      latitudes toward the North Atlantic. From the mid-1990s the sub-thermocline
      southern Indian Ocean experienced a rapid temperature trend reversal. Here we
      show, using climate models from phase 5 of the Coupled Model Intercomparison
      Project, that the late twentieth century sub-thermocline cooling of the southern
      Indian Ocean was primarily driven by increasing anthropogenic aerosols and
      greenhouse gases. The models simulate a slow-down in the sub-thermocline cooling
      followed by a rapid warming towards the mid twenty-first century. The simulated
      evolution of the Indian Ocean temperature trend is linked with the peak in
      aerosols and their subsequent decline in the twenty-first century, reinforcing
      the hypothesis that aerosols influence ocean circulation trends. 

PMID- 23873280
TI  - Changes in academic adjustment and relational self-worth across the transition to
      middle school.
AB  - Moving from elementary to middle school is a time of great transition for many
      early adolescents. The present study examined students' academic adjustment and
      relational self-worth at 6-month intervals for four time points spanning the
      transition from elementary school to middle school (N = 738 at time 1; 53 %
      girls; 54 % African American, 46 % European American). Grade point average
      (G.P.A.), intrinsic value for schoolwork, self-worth around teachers, and self
      worth around friends were examined at every time point. The overall developmental
      trajectory indicated that G.P.A. and intrinsic value for schoolwork declined. The
      overall decline in G.P.A. was due to changes at the transition and across the
      first year in middle school. Intrinsic value declined across all time points.
      Self-worth around teachers was stable. The developmental trends were the same
      regardless of gender or ethnicity except for self-worth around friends, which was
      stable for European American students and increased for African American students
      due to an ascent at the transition into middle school. Implications for the
      education of early adolescents in middle schools are discussed.

PMID- 23873282
TI  - Successful allogeneic stem cell transplantation with long-term remission of
      ETV6/FLT3-positive myeloid/lymphoid neoplasm with eosinophilia.

PMID- 23873283
TI  - Insulin-like effect of the phosphodiesterase type 5 inhibitor tadalafil onto male
      human skeletal muscle cells.
AB  - BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5i), widely used to treat
      male erectile dysfunction, seem to counteract insulin resistance (IR) in animals
      and humans. IR, primarily manifest in peripheral tissues and particularly in
      skeletal muscle, is due to impaired insulin signal transduction. Investigators
      have been focusing onto intracellular defects responsible for IR to identify
      suitable pharmacological tools targeted toward the specific defects. Albeit some
      effects of PDE5i have been reported onto animal muscular tissues or cells,
      whether and how they might affect metabolic processes directly in human skeletal
      muscle still remains unclear. AIM: We aimed to investigate in human fetal
      skeletal muscle cells (Hfsmc) the effect of tadalafil, one of PDE5i, onto some
      intracellular factors involved in response to insulin, such as ras-raf mitogen
      activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B
      (PKB/Akt), glycogen synthase kinase 3beta (GSK-3beta), and the transcriptional
      factor c-Myc; proliferation rate; lactate (lact) and free fatty acid (ffa)
      release; activity of citrate synthase (CS) and succinate dehydrogenase (SDH),
      both enzymes of Kreb's cycle; PDE5 gene expression. MATERIALS AND METHODS:
      Western blot analysis, enzyme-linked immunosorbent assay, enzymatic assays, cell
      count, MTT assay and Real Time PCR were performed in Hfsmc with and without
      tadalafil. RESULTS: In Hfsmc tadalafil affected the insulin-related intracellular
      cascade, by increasing MAPK, PKB/Akt, GSK-3beta phosphorylation and c-Myc
      expression. ffa release and CS activity also significantly increased, with no
      changes in SDH activity and lact release. CONCLUSIONS: Tadalafil, like insulin,
      targeted part of the machinery dedicated to energy management and metabolic
      control in human skeletal muscle cells.

PMID- 23873284
TI  - Metal-free oxidative hydroxyalkylarylation of activated alkenes by direct sp3 C-H
      functionalization of alcohols.
AB  - A metal-free tandem radical addition/cyclization reaction of activated alkenes
      and alcohols has been developed. The process provides an efficient and atom
      economical access to various valuable hydroxyl-containing oxindoles through the
      direct sp(3) C-H functionalization of alcohols. 

PMID- 23873285
TI  - Review of direct renin inhibition by aliskiren.
AB  - Numerous clinical studies have been conducted to analyse the ability of renin
      angiotensin system blockade to lower blood pressure and to reduce end-organ
      damage. In addition to angiotensin-converting enzyme inhibitors and angiotensin
      receptor blockers, direct renin inhibitors emerged as an attractive option to
      inhibit the renin-angiotensin system and thus to prevent cardiovascular damage.
      Based on the publication of the most recent available results of ALTITUDE and
      ASTRONAUT, we review the data with respect to the direct renin inhibitor
      aliskiren given as an antihypertensive drug, in monotherapy and combination
      therapy, and the most recent publication analysing the effects of aliskiren on
      end-organ protection. 

PMID- 23873286
TI  - Assessment of CYP3A-mediated drug-drug interaction potential for victim drugs
      using an in vivo rat model.
AB  - The present study aims to determine if an in vivo rat model of drug-drug
      interaction (DDI) could be useful to discriminate a sensitive (buspirone) from a
      'non-sensitive' (verapamil) CYP3A substrate, using ketoconazole and ritonavir as
      perpetrator drugs. Prior to in vivo studies, ketoconazole and ritonavir were
      shown to inhibit midazolam hydroxylation with IC50 values of 350 +/- 60 nm and 11
      +/- 3 nm, respectively, in rat liver microsomes (RLM). Buspirone and verapamil
      were also shown to be substrates of recombinant rat CYP3A1/3A2. In the rat model,
      the mean plasma AUC0-inf of buspirone (10 mg/kg, p.o.) was increased by 7.4-fold
      and 12.8-fold after co-administration with ketoconazole and ritonavir (20 mg/kg,
      p.o.), respectively. The mean plasma AUC0-inf of verapamil (10 mg/kg, p.o.) was
      increased by 3.0-fold and 4.8-fold after co-administration with ketoconazole and
      ritonavir (20 mg/kg, p.o.), respectively. Thus, the rat DDI model correctly
      identified buspirone as a sensitive CYP3A substrate (>5-fold AUC change) in
      contrast to verapamil. In addition, for both victim drugs, the extent of DDI when
      co-administered was greater with ritonavir compared with ketoconazole, in line
      with their in vitro CYP3A inhibition potency in RLM. In conclusion, our study
      extended the rat DDI model applicability to two additional victim/perpetrator
      pairs. In addition, we suggest that use of this model would increase our
      confidence in estimation of the DDI potential for victim drugs in early
      discovery.

PMID- 23873288
TI  - Polybrominated diphenyl ethers in human hair from the college environment:
      comparison with indoor dust.
AB  - Eight Polybrominated diphenyl ether (PBDE) congeners (BDE 28, 47, 99, 100, 153,
      154, 183 and 209) were determined to examine the hair burden at low
      concentrations, and the relationship between PBDE concentrations in human hair
      and indoor dust from a college environment (Shanghai University campus). Chemical
      analyses showed that the total concentrations of PBDEs in hair ranged from 4.04
      to 99 ng/g dw, and were found to be fourfold higher in females than in males (p <
      0.05). The total PBDEs concentrations in indoor dust samples ranged from 170 to
      1,360 ng/g dw. Significantly positive correlations were observed between human
      hair and indoor dust for BDE 47 (r = 0.44, p = 0.048) and BDE 99 (r = 0.68, p =
      0.025). However, no significant association was noted between other PBDE
      congeners in human hair and indoor dust in the present study. 

PMID- 23873289
TI  - FEATURE RANKING BASED NESTED SUPPORT VECTOR MACHINE ENSEMBLE FOR MEDICAL IMAGE
      CLASSIFICATION.
AB  - This paper presents a method for classification of structural magnetic resonance
      images (MRI) of the brain. An ensemble of linear support vector machine
      classifiers (SVMs) is used for classifying a subject as either patient or normal
      control. Image voxels are first ranked based on the voxel wise t-statistics
      between the voxel intensity values and class labels. Then voxel subsets are
      selected based on the rank value using a forward feature selection scheme.
      Finally, an SVM classifier is trained on each subset of image voxels. The class
      label of a test subject is calculated by combining individual decisions of the
      SVM classifiers using a voting mechanism. The method is applied for classifying
      patients with neurological diseases such as Alzheimer's disease (AD) and autism
      spectrum disorder (ASD). The results on both datasets demonstrate superior
      performance as compared to two state of the art methods for medical image
      classification.

PMID- 23873287
TI  - Regulation of Golgi signaling and trafficking by the KDEL receptor.
AB  - Intracellular membrane transport involves the well-coordinated engagement of a
      series of organelles and molecular machineries that ensure that proteins are
      delivered to their correct cellular locations according to their function. To
      maintain the homeostasis of the secretory system, the fluxes of membranes and
      protein across the transport compartments must be precisely balanced. This
      control should rely on a mechanism that senses the movement of the traffic and
      generates the required homeostatic response. Due to its central position in the
      secretory pathway and to the large amounts of signaling molecules associated with
      it, the Golgi complex represents the ideal candidate for this regulation. The
      generation of autonomous signaling by the Golgi complex in response to the
      arrival of cargo from the endoplasmic reticulum (ER) has been experimentally
      addressed only in recent years. These studies have revealed that cargo moving
      from the ER to the Golgi activates a series of signaling pathways, the functional
      significance of which appears to be to maintain the homeostasis of the Golgi
      complex and to activate Golgi trafficking according to internal demand. We have
      termed this regulatory mechanism the Golgi control system. A key player in this
      Golgi control system is the KDEL receptor, which has previously been shown to
      retrieve chaperones back to the endoplasmic reticulum and more recently to behave
      as a signaling receptor. Here, we discuss the particular role of KDEL receptor
      signaling in the regulation of important pathways involved in the maintenance of
      the homeostasis of the transport apparatus, and in particular, of the Golgi
      complex. 

PMID- 23873290
TI  - Prescribing patterns of lithium or lithium+valproate in manic or mixed episodes:
      a naturalistic study.
AB  - The present study aimed to identify the prescribing patterns of lithium or of
      lithium+valproate in 75 bipolar I outpatients in a manic or a mixed phase within
      a naturalistic setting. The differences between the two treatments and the
      correlation between serum lithium levels and response were also examined. The
      results showed that patients with lithium levels of 0.60 mEq/l or more had higher
      remission rates and greater symptom reduction than the other patients. Patients
      on lithium and valproate showed greater improvement in mixed, anxiety, and
      psychotic symptoms than those on lithium only, as assessed by the Clinical Global
      Impression-Bipolar version scale scores. Finally, our findings suggest that a
      range of lithium levels between 0.40 and 0.60 mEq/l, albeit below the therapeutic
      range, seems sufficient to maintain a good effect when lithium is coadministered
      with valproate. 

PMID- 23873291
TI  - Relationship between major depressive disorder and associated painful physical
      symptoms: analysis of data from two pooled placebo-controlled, randomized studies
      of duloxetine.
AB  - The aim of this study was to evaluate the relationship between painful physical
      symptoms (PPS) and outcomes in major depressive disorder (MDD). Post-hoc analysis
      of two identically designed 8-week trials compared the efficacy of 60 mg/day
      duloxetine (N=523) with that of placebo (N=532) in treating PPS associated with
      MDD. The Montgomery-Asberg Depression Rating Scale (MADRS) total score, the Brief
      Pain Inventory (BPI) average pain score, and the Sheehan Disability Scale global
      functional impairment score assessed depression symptoms, pain, and functioning,
      respectively. Remission was defined as a MADRS score of 10 or less, and the BPI
      response subgroup was defined as a 50% or greater reduction from baseline. Path
      analyses assessed relationships among variables. Duloxetine-treated patients who
      had a 50% or greater reduction in BPI score at endpoint had higher rates of
      remission. Path analysis indicated that 16% of likelihood of remission in
      depression symptoms was because of the direct effect of treatment, 41% because of
      pain reduction, and 43% because of functional improvement. Path analysis also
      indicated that 51% of improvement in functioning was attributed to pain
      improvement and 43% to mood improvement. Results demonstrate that improvement in
      pain and mood contributes to functional improvement, and pain reduction and
      functional improvement increase the likelihood of remission of depressive
      symptoms with duloxetine treatment in patients with both MDD and PPS at baseline.

PMID- 23873292
TI  - The prevalence and management of side effects of lithium and anticonvulsants as
      mood stabilizers in bipolar disorder from a clinical perspective: a review.
AB  - Side effects are among the most frequent reasons preventing patients from taking
      their medication. Although the management of side effects is an important issue
      in clinical practice, particularly in patients with physical comorbidities,
      research on clinical management of side effects is rather scattered. The aim of
      this article was to provide an overview on the prevalence and management of
      various side effects of mood-stabilizing drugs. In December 2012, we carried out
      a PubMed search for publications reporting side effects in patients with bipolar
      disorder. Naturalistic studies describing the prevalence of side effects in
      treatment with mood stabilizers are sparse. We describe the prevalence of
      neurological, gastrointestinal, metabolic, thyroid, dermatological, nephrogenic,
      cognitive, sexual, hematological, hepatogenic, and teratogenic side effects of
      lithium, valproate, carbamazepine, and lamotrigine and discuss their clinical
      management. There are specific strategies that aim at reducing side effects, but,
      to date, studies on the efficacy of these interventions are lacking. With age,
      the renal elimination and hepatic metabolism of drugs reduce and comedication and
      somatic comorbidity increase, making elderly patients particularly susceptible to
      side effects. Most side effects can be managed by striving for the lowest
      possible dose without losing efficacy by lowering the dose below the therapeutic
      window. Specific measurements to limit certain side effects are available and may
      ameliorate treatment adherence. 

PMID- 23873293
TI  - Aripiprazole augmentation for treatment of patients with chronic or recurrent
      major depressive disorder: a 12-week prospective open-label multicentre study.
AB  - Patients with chronic or recurrent major depressive disorder (MDD) have faced a
      dearth of treatment options. The present study evaluated the effectiveness and
      tolerability of aripiprazole augmentation for the treatment of chronic or
      recurrent MDD. This was the first 12-week prospective, multicentre, open-label
      study of the effectiveness and tolerability of flexibly dosed aripiprazole as an
      augmentation to ongoing antidepressant treatment in patients with chronic or
      recurrent MDD. The primary outcome measure for effectiveness was changes between
      baseline and endpoint (week 12) in total scores on the Montgomery-Asberg
      Depression Rating Scale. Adverse events (AEs) occurring throughout the trial are
      also reported. The Montgomery-Asberg Depression Rating Scale total scores
      decreased significantly between the baseline and the endpoint (magnitude of
      difference=-11.6, P<0.0001). At the endpoint, the response rate was 55.2% and the
      remission rate was 41.3%. Adjunctive aripiprazole treatment administered from
      week 1 through the endpoint was associated with remission and significant
      treatment responses. More than half (55.8%) of those taking adjunctive
      aripiprazole completed the study and relatively few patients discontinued
      participation because of AEs. None of the patients discontinued participation in
      the study because of an inadequate therapeutic response. Common AEs included
      headache, akathisia, insomnia and constipation. The mean dose of aripiprazole at
      the endpoint was 6.6 mg/day. Adjunctive aripiprazole may be effective and
      tolerable for patients with chronic or recurrent MDD. Adequately powered and
      controlled clinical trials should be conducted to confirm our open-label study
      findings. 

PMID- 23873294
TI  - Induced production of 1-methoxy-indol-3-ylmethyl glucosinolate by jasmonic acid
      and methyl jasmonate in sprouts and leaves of pak choi (Brassica rapa ssp.
      chinensis).
AB  - Pak choi plants (Brassica rapa ssp. chinensis) were treated with different
      signaling molecules methyl jasmonate, jasmonic acid, linolenic acid, and methyl
      salicylate and were analyzed for specific changes in their glucosinolate profile.
      Glucosinolate levels were quantified using HPLC-DAD-UV, with focus on induction
      of indole glucosinolates and special emphasis on 1-methoxy-indol-3-ylmethyl
      glucosinolate. Furthermore, the effects of the different signaling molecules on
      indole glucosinolate accumulation were analyzed on the level of gene expression
      using semi-quantitative realtime RT-PCR of selected genes. The treatments with
      signaling molecules were performed on sprouts and mature leaves to determine
      ontogenetic differences in glucosinolate accumulation and related gene
      expression. The highest increase of indole glucosinolate levels, with
      considerable enhancement of the 1-methoxy-indol-3-ylmethyl glucosinolate content,
      was achieved with treatments of sprouts and mature leaves with methyl jasmonate
      and jasmonic acid. This increase was accompanied by increased expression of genes
      putatively involved in the indole glucosinolate biosynthetic pathway. The high
      levels of indole glucosinolates enabled the plant to preferentially produce the
      respective breakdown products after tissue damage. Thus, pak choi plants treated
      with methyl jasmonate or jasmonic acid, are a valuable tool to analyze the
      specific protection functions of 1-methoxy-indole-3-carbinole in the plants
      defense strategy in the future. 

PMID- 23873295
TI  - Effect of a static magnetic fields and fluoride ions on the antioxidant defense
      system of mice fibroblasts.
AB  - The results of studies on the biological influence of magnetic fields are
      controversial and do not provide clear answers regarding their impact on cell
      functioning. Fluoride compounds are substances that influence free radical
      processes, which occur when the reactive forms of oxygen are present. It is not
      known whether static magnetic fields (SMF) cause any changes in fluoride
      assimilation or activity. Therefore, the aim of this work was to determine the
      potential relationship between magnetic field exposure to, and the antioxidant
      system of, fibroblasts cultured with fluoride ions. Three chambers with static
      magnetic fields of different intensities (0.4, 0.6, and 0.7 T) were used in this
      work. Fluoride ions were added at a concentration of 0.12 mM, which did not cause
      the precipitation of calcium or magnesium. The results of this study show that
      static magnetic fields reduce the oxidative stress caused by fluoride ions and
      normalize the activities of antioxidant enzymes, including superoxide dismutase
      (SOD), glutathione peroxidase (GPx), and catalase (CAT). Static magnetic fields
      modify the energy state of fibroblasts, causing an increase in the ATP
      concentration and a decrease in the MDA concentration. These results suggest that
      exposure to fluoride and an SMF improves the tolerance of cells to the oxidative
      stress induced by fluoride ions. 

PMID- 23873296
TI  - DNA methylation and cancer diagnosis.
AB  - DNA methylation is a major epigenetic modification that is strongly involved in
      the physiological control of genome expression. DNA methylation patterns are
      largely modified in cancer cells and can therefore be used to distinguish cancer
      cells from normal tissues. This review describes the main technologies available
      for the detection and the discovery of aberrantly methylated DNA patterns. It
      also presents the different sources of biological samples suitable for DNA
      methylation studies. We discuss the interest and perspectives on the use of DNA
      methylation measurements for cancer diagnosis through examples of methylated
      genes commonly documented in the literature. The discussion leads to our
      consideration for why DNA methylation is not commonly used in clinical practice
      through an examination of the main requirements that constitute a reliable
      biomarker. Finally, we describe the main DNA methylation inhibitors currently
      used in clinical trials and those that exhibit promising results. 

PMID- 23873297
TI  - Epigenetics meets radiation biology as a new approach in cancer treatment.
AB  - Cancer is a disease that results from both genetic and epigenetic changes. In
      recent decades, a number of people have investigated the disparities in gene
      expression resulting from variable DNA methylation alteration and chromatin
      structure modification in response to the environment. Especially, colon cancer
      is a great model system for investigating the epigenetic mechanism for aberrant
      gene expression alteration. Ionizing radiation (IR) could affect a variety of
      processes within exposed cells and, in particular, cause changes in gene
      expression, disruption of cell cycle arrest, and apoptotic cell death. Even
      though there is growing evidence on the importance of epigenetics and biological
      processes induced by radiation exposure in various cancer types including colon
      cancer, specific epigenetic alterations induced by radiation at the molecular
      level are incompletely defined. This review focuses on discussing possible IR
      mediated changes of DNA methylation and histone modification in cancer. 

PMID- 23873298
TI  - Defective homocysteine metabolism: potential implications for skeletal muscle
      malfunction.
AB  - Hyperhomocysteinemia (HHcy) is a systemic medical condition and has been
      attributed to multi-organ pathologies. Genetic, nutritional, hormonal, age and
      gender differences are involved in abnormal homocysteine (Hcy) metabolism that
      produces HHcy. Homocysteine is an intermediate for many key processes such as
      cellular methylation and cellular antioxidant potential and imbalances in Hcy
      production and/or catabolism impacts gene expression and cell signaling including
      GPCR signaling. Furthermore, HHcy might damage the vagus nerve and superior
      cervical ganglion and affects various GPCR functions; therefore it can impair
      both the parasympathetic and sympathetic regulation in the blood vessels of
      skeletal muscle and affect long-term muscle function. Understanding cellular
      targets of Hcy during HHcy in different contexts and its role either as a primary
      risk factor or as an aggravator of certain disease conditions would provide
      better interventions. In this review we have provided recent Hcy mediated
      mechanistic insights into different diseases and presented potential implications
      in the context of reduced muscle function and integrity. Overall, the impact of
      HHcy in various skeletal muscle malfunctions is underappreciated; future studies
      in this area will provide deeper insights and improve our understanding of the
      association between HHcy and diminished physical function. 

PMID- 23873299
TI  - X linked agammaglobulinemia: a single centre experience from India.
AB  - The authors report a series of seven cases of X-linked Agammaglobulinemia,
      diagnosed and receiving treatment at a tertiary care centre in Mumbai. The ages
      of the patients ranged from 15 mo to 15 y. After diagnosis at a mean age of 3 1/2
      y, all were advised intravenous immunoglobulin (IvIg) infusion therapy in doses
      of 400-600 mg/kg every 3-4 wk. They were followed up for an average duration of 9
      y, throughout which the complications and overall response to immunoglobulin
      therapy have been observed. The clinical profiles of each of these cases were
      retrospectively analysed with respect to age at diagnosis, frequency and severity
      of infections before and after initiation of treatment, co-morbidities and
      response to therapy. The results demonstrate the importance of early diagnosis
      and its correlation with decreased complications. 

PMID- 23873300
TI  - Risk factors for severe acute malnutrition in children below 5 y of age in India:
      a case-control study.
AB  - OBJECTIVE: To determine the possible risk factors for severe acute malnutrition
      (SAM) in children below 5 y admitted in a hospital in north India. METHODS: This
      case-control study was conducted in a medical college hospital in children below
      5 y of age. All cases of SAM (diagnosed as per WHO definition) between 6 and 59
      mo of age were compared with age-matched controls with weight for height above 
      2SD of WHO 2006 growth standards. Data regarding socio-demographic parameters,
      feeding practices and immunization were compared between the groups by
      univariable and multivariable logistic regression models. RESULTS: A total of 76
      cases and 115 controls were enrolled. Among the 14 factors compared, maternal
      illiteracy, daily family income less than Rs. 200, large family size, lack of
      exclusive breast feeding in first 6 mo, bottle feeding, administration of pre
      lacteals, deprivation of colostrum and incomplete immunization were significant
      risk factors for SAM. Regarding complementary feeding, it was the consistency,
      rather than the age of initiation, frequency and variety which showed a
      significant influence on occurrence of SAM. Multivariate analysis revealed that
      the risk of SAM was independently associated with 6 factors, namely, illiteracy
      among mothers, incomplete immunization, practice of bottle feeding, consistency
      of complementary feeding, deprivation of colostrum and receipt of pre-lacteals at
      birth. CONCLUSIONS: The present study identifies certain risk factors which need
      to be focused on during health planning and policy making related to children
      with SAM in India.

PMID- 23873301
TI  - Multiple palpable nodules: do not miss the great toes.

PMID- 23873302
TI  - Transfusion in sickle cell disease: experience from a Gujarat centre.
AB  - OBJECTIVES: Following impressions that the use of blood transfusion in sickle
      cell disease may be inappropriately high, transfusion practice at a major blood
      bank in an area of high prevalence of sickle cell disease was assessed. METHODS:
      Retrospective review of blood usage in sickle cell disease at a major blood bank
      in south Gujarat in 2010 was conducted with prospective more detailed data
      collection over 18 wk period (April 7 through August 15) in 2011. The results
      were compared with transfusion usage in the Jamaican Sickle Cell Clinic. RESULTS:
      In 2010, this blood bank processed a total of 19,037 units of which 384 (5.2 %)
      units were for patients with sickle cell disease. Median transfusion use was 1
      unit but 16 patients (4.2 %) of those transfused received 10 units or more and
      five patients received over 20 units. More detailed prospective analysis revealed
      that most transfusions occurred between ages 5-15 y, 40 % of subjects had
      pretransfusion hemoglobin levels below 6 g/dL, symptoms were generally vague such
      as fever, bone pain, weakness and that 26 % denied any specific symptoms.
      CONCLUSIONS: Transfusion usage greatly exceeds that in the Jamaican Sickle Cell
      Clinic. Transfusion therapy carries risks and cost and more detailed
      investigation and diagnosis of anemic episodes is necessary to define the role of
      transfusion among other potential therapies. Eventually, guidelines evolved by
      Indian specialists should determine the indications for transfusion in sickle
      cell disease.

PMID- 23873303
TI  - Evidence for the antagonistic form of CXC-motif chemokine CXCL10 in serous
      epithelial ovarian tumours.
AB  - Patients with high-grade, serous epithelial ovarian carcinoma (HGSOC) are
      generally diagnosed with extensive peritoneal metastases, and exhibit 5-year
      survival rates <30%. A subset of these tumours, defined as "immunoreactive,"
      overexpress mRNA encoding the T-cell-recruiting chemokine CXCL10 (10-kDa
      interferon gamma-induced protein; C-X-C motif chemokine 10). Tumour-infiltrating
      CD4(+) CD8(+) T-cells are a well-documented, positive prognostic indicator for
      HGSOC patients; paradoxically, however, patients diagnosed with HGSOC
      (overexpressing CXCL10 and therefore theorised to recruit T-cells) typically
      exhibit poor survival. Recently, an "antagonistic" CXCL10 variant was identified
      that inhibited leucocyte recruitment to inflamed liver in vivo (Casrouge et al.,
      J Clin Invest 2011;121:308-17). We hypothesised that "immunoreactive" HGSOC might
      also express antagonistic CXCL10, interfering with leucocyte recruitment and
      contributing to poor patient prognosis. CXCL10 expression was analysed in HGSOC
      tissues grouped according to pathology, grade and FIGO stage at diagnosis, and
      its localisation and association with T-cells established by immunohistochemical
      staining in tissue microarrays. CXCL10 expression was increased in a subset of
      serous epithelial tumour samples; however, it did not correlate well with CD45
      positive tumour infiltrate. Immunoprecipitation and de novo sequence analysis of
      CXCL10 identified the N-terminally cleaved, "antagonistic" variant of CXCL10
      specifically in malignant tumours, and not in benign ovarian disease. The data
      demonstrate the presence of the antagonistic form of CXCL10 in HGSOC for the
      first time, and provide a partial explanation for reduced leucocyte infiltration
      observed in these tumours. We suggest that CXCL10 cleavage and subsequent
      antagonism of immune cell recruitment may be a feature of the "immunoreactive"
      HGSOC subtype, leading to early impairment of the immune response and
      subsequently worsening patient prognosis. 

PMID- 23873304
TI  - Implantable electrolyte conductance-based pressure sensing catheter, I. Modeling.
AB  - Direct measurements of arterial blood pressure most commonly use bulky external
      instrumentation containing a pressure transducer connected to an ex vivo fluid
      filled arterial line, which is subject to several sensing artifacts. In situ
      blood pressure sensors, typically solid state piezoresistive, capacitive, and
      interferometric sensors, are unaffected by these artifacts, but can be expensive
      to produce and miniaturize. We have developed an alternative approach to blood
      pressure measurement based on deformation of an elastic tube filled with
      electrolyte solution. We have constructed an analytical model describing the
      deformation of a fluid-filled tube part of which is exposed to external pressure,
      with the remaining part unexposed. The model predicts pressure-induced change in
      dimension of the internal electrolyte-filled volume and a resultant change in its
      electrical resistance, which can be measured to determine the pressure and is the
      basis for the sensor operation. We have applied the model to find the pressure
      sensitivity of fractional change in resistance as a function of device material
      and dimensional parameters. Construction and testing of a device is described in
      the following paper. 

PMID- 23873305
TI  - A molecular dynamics simulation study of the electric double layer and
      capacitance of [BMIM][PF6] and [BMIM][BF4] room temperature ionic liquids near
      charged surfaces.
AB  - A molecular dynamics simulation study of electric double layer (EDL) structure
      and differential capacitance (DC) of two 1-butyl-3-methylimidazolium (BMIM)-based
      room temperature ionic liquids, i.e. [BMIM][BF4] and [BMIM][PF6], has been
      conducted on basal and prismatic graphite as well as (001) and (011) gold
      electrode surfaces. The influence of the electrode surface and electrolyte
      structure on electrode capacitance and EDL structure are discussed. For a given
      electrode surface both the [BMIM][BF4] and [BMIM][PF6] electrolytes generate very
      similar DC and EDL structures. The DC for these ionic liquids in contact with
      atomically flat surfaces (i.e. basal graphite and (001)Au) shows very small
      variations within the electrolyte chemical stability potential window and
      fluctuates around an average value of ~5 MUF cm(-2). On atomically more
      corrugated surfaces (i.e., Au(011) and prismatic graphite) the DC shows more
      variation with electrode potential and depends on the correspondence between
      dimensions of the surface roughness and electrolyte ion sizes. The trends and
      dependencies obtained for DC are used to discriminate between mutually
      contradictory experimental data reported in the literature for related systems. 

PMID- 23873307
TI  - Base excision repair capacity in chronic renal failure patients undergoing
      hemodialysis treatment.
AB  - The aim of this study was to determine if the differences observed in the levels
      of DNA damage in a group of patients suffering from chronic renal failure are due
      to differences in the repair capability. DNA damage was initially measured with
      the comet assay in 106 hemodialysis patients. A selected group of 21 patients
      representing high (ten patients) and low (11 patients) levels of DNA damage were
      obtained for determination of base excision repair capacity. This was measured in
      an in vitro assay where protein extracts from lymphocytes were incubated with a
      substrate of DNA containing 8-oxoguanine, and the rate of incision was measured
      with the comet assay. Patients with high levels of genomic damage showed, as an
      average, significantly lower repair capacity (12.73 +/- 1.84) in comparison with
      patients with low levels of genomic damage (18.13 +/- 1.13). Nevertheless, the
      correlation coefficient between repair ability and levels of genomic damage was
      found to be only close to the significance value (r:-0.423, p: 0.056). Although
      DNA damage was clearly related to time on hemodialysis, base excision repair
      capacity was not. This is one of the few studies providing information on the
      repair capacity of chronic renal failure patients undergoing hemodialysis. As a
      summary, our results would indicate that DNA damage levels are in part associated
      to the repair capacity of the patients, and this repair capacity is not
      associated with the duration of hemodialysis treatment.

PMID- 23873306
TI  - Small molecules enable neurogenin 2 to efficiently convert human fibroblasts into
      cholinergic neurons.
AB  - Cell fate can be reprogrammed by modifying intrinsic and extrinsic cues. Here we
      show that two small molecules (forskolin and dorsomorphin) enable the
      transcription factor Neurogenin 2 (NGN2) to convert human fetal lung fibroblasts
      into cholinergic neurons with high purity (>90%) and efficiency (up to 99% of
      NGN2-expressing cells). The conversion is direct without passing through a
      proliferative progenitor state. These human induced cholinergic neurons (hiCN)
      show mature electrophysiological properties and exhibit motor neuron-like
      features, including morphology, gene expression and the formation of functional
      neuromuscular junctions. Inclusion of an additional transcription factor, SOX11,
      also efficiently converts postnatal and adult skin fibroblasts from healthy and
      diseased human patients to cholinergic neurons. Taken together, this study
      identifies a simple and highly efficient strategy for reprogramming human
      fibroblasts to subtype-specific neurons. These findings offer a unique venue for
      investigating the molecular mechanisms underlying cellular plasticity and human
      neurodegenerative diseases. 

PMID- 23873308
TI  - Physical-chemistry at the cross-road of advanced oxide materials.

PMID- 23873309
TI  - Low heart rates predict incident atrial fibrillation in healthy middle-aged men.
AB  - BACKGROUND: Low resting heart rate (HR) has been associated with atrial
      fibrillation (AF) in athletes. We aimed to study whether low HR at rest or during
      exercise testing was a predictor of AF in initially healthy middle-aged men.
      METHODS AND RESULTS: A total of 2014 healthy Norwegian men participated in a
      prospective cardiovascular survey, including a standardized bicycle exercise test
      in 1972 to 1975. During <=35 years of follow-up (53,000 person-years of
      observation), 270 men developed incident AF, documented by scrutiny of health
      charts in all Norwegian hospitals. Risk estimation was analyzed with Cox
      proportional hazard models. Low exercise HR after 6 minutes exercise on the
      moderate workload of 100 W (HR100W) was a predictor of incident AF. Men with
      HR100W <100 beats per minute (n=260) were characterized by high physical fitness,
      low resting and low maximum HR, and they had 1.60-fold AF risk (95% confidence
      interval, 1.11-2.26) compared with men with HR100W >=100 beats per minute when
      adjusted for age, systolic blood pressure, and physical fitness. Additional
      adjustment for relative heart volume slightly reduced the association. The
      subgroup of men (n=860) with hypertensive blood pressure measurements at baseline
      had the highest risk difference between low and high HR100W with hazard ratio
      2.08 (1.19-3.45). CONCLUSIONS: Our data indicate that low exercise HR on a
      moderate workload is a long-term predictor of incident AF in healthy middle-aged
      men. Elevated baseline blood pressure substantially amplifies this risk. The
      present results suggest a relationship between increased vagal tone, high stroke
      volumes and incident AF, and particularly so in physically fit men.

PMID- 23873310
TI  - The impact of p53 in predicting clinical outcome of breast cancer patients with
      visceral metastasis.
AB  - In the study, we analyzed role of p53 in predicting outcome in visceral
      metastasis breast cancer (VMBC) patients. 97 consecutive VMBC patients were
      studied. P53 positivity rate was 29.9%. In the p53-negative group, median disease
      free survival (DFS), and time from primary breast cancer diagnosis to death
      (OS1), time from metastases to death (OS2) were 25, 42.5, and 13.5 months,
      respectively. In the p53-positive group, they were 10, 22, and 8 months,
      respectively. Statistically significant differences in DFS and OS1 were detected
      between the p53-negative and p53-positive subtypes. However, p53 appears to have
      no influence on OS2. In Cox regression analysis, p53 expression and TNM stage
      were predictive factors of DFS. In the multivariate analysis, p53 expression and
      the duration of DFS correlated with OS1, but not for OS2. Taken together, our
      data indicate p53 showing predicting role in OS1 for VMBC, but not for OS2. 

PMID- 23873311
TI  - The regulation and function of the NUAK family.
AB  - AMP-activated protein kinase (AMPK) is a critical regulator of cellular and whole
      body energy homeostasis. Twelve AMPK-related kinases (ARKs; BRSK1, BRSK2, NUAK1,
      NUAK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4, and MELK) have been identified
      recently. These kinases show a similar structural organization, including an N
      terminal catalytic domain, followed by a ubiquitin-associated domain and a C
      terminal spacer sequence, which in some cases also contains a kinase-associated
      domain 1. Eleven of the ARKs are phosphorylated and activated by the master
      upstream kinase liver kinase B1. However, most of these ARKs are largely unknown,
      and the NUAK family seems to have different regulations and functions. This
      review contains a brief discussion of the NUAK family including the specific
      characteristics of NUAK1 and NUAK2. 

PMID- 23873312
TI  - Treatment of symptomatic carotid stenosis: carotid stent placement versus
      endarterectomy.
AB  - The mainstay of treatment options for symptomatic carotid stenosis is focused
      around medical management, carotid endarterectomy, and carotid angioplasty and
      stent placement. The International Carotid Stenting Study (ICSS), also called
      Carotid and Vertebral Artery Transluminal Angioplasty Study 2 (CAVATAS 2), the
      Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus
      Endarterectomy (SPACE) trial, the Endarterectomy Versus Angioplasty in Patients
      with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stenting and
      Angioplasty with Protection in Patients at High Risk for Endarterectomy
      (SAPPHIRE) trial, and the Carotid Revascularization Endarterectomy Versus
      Stenting Trial (CREST) were five major trials which compared carotid
      endarterectomy and carotid angioplasty and stent placement. We review the results
      of the trials and incorporation of the results into clinical decision making. 

PMID- 23873313
TI  - Advances in the treatment of primary and secondary immune deficiences.

PMID- 23873314
TI  - Pharmacoeconomics of immunoglobulins and indications for their use.

PMID- 23873315
TI  - Management of secondary immune deficiencies: what is the role of immunoglobulins?

PMID- 23873316
TI  - Primary immune deficiencies: practical questions.

PMID- 23873317
TI  - Incidence of bicompartmental osteoarthritis in patients undergoing total and
      unicompartmental knee arthroplasty: is the time ripe for a less radical
      treatment?
AB  - We sought to determine the incidence of bicompartmental osteoarthritis among knee
      replacement patients for possible bone-sparing procedures. In 259 consecutive
      Knee Registry subjects undergoing total or unicondylar knee arthroplasty, all
      three compartments of the knee joint were evaluated. Radiographic images and
      preoperative cruciate ligaments assessment combined with intraoperative cartilage
      grading using Outerbridge classification was implemented for patients'
      evaluations. Among the candidates for knee replacement arthroplasty, 59% had
      osteoarthritis in all three compartments, 28% had bicompartmental disease, and 4%
      had unicompartmental disease. Nine percent of patients exhibited inconclusive
      osteoarthritis pattern. Only 5% of the patients were found to have cruciate
      ligaments impairment. Older patients ( > 65 years) were significantly more likely
      to have bi- and tricompartmental disease. We had found that 28% of our registry
      population had bicompartmental disease and infrequent impairment of cruciate
      ligaments, indicating that between one-fourth and one-third of patients
      undergoing total knee arthroplasty could be considered for bone preserving
      bicompartmental knee arthroplasty.

PMID- 23873318
TI  - No conclusive evidence that histologically found granulomas and acute local
      reactions following hylan G-F 20 injections are related or have clinical
      significance.
AB  - Osteoarthritic (OA) knee pain can be successfully treated with hylan G-F 20
      (Synvisc, Sanofi Biosurgery, Cambridge, MA) with few local adverse events.
      However, a few studies have identified hyaluronate positive (HA+) granulomas in
      the synovial tissue of patients treated with hylan G-F 20 raising the question of
      their relationship and clinical significance. To understand the potential
      relationship of HA+ granulomas with the occurrence of acute local reactions
      (ALRs), we evaluated the synovial tissue of OA patients undergoing total knee
      replacement that had previously been treated with hylan G-F 20 (n = 101) or had
      not been treated (n = 20). Granulomas were observed in nine patients, of which
      eight were in the hylan G-F 20 group (7.9%); HA+ granulomas were identified in
      six of these eight patients (5.9%). Three of the six patients with HA+ granulomas
      experienced an ALR within 30 days of administering an injection. Overall, we
      found no consistent relationship between histologically found HA+ granulomas and
      the occurrence of an ALR following hylan G-F 20 treatment. These microscopic
      granulomas were not associated with any symptoms and likely have little clinical
      significance. The low occurrence of granulomas and/or ALRs should not preclude
      use of hylan G-F 20 for the treatment of knee pain associated with OA. 

PMID- 23873319
TI  - The effect of pH and fluoride concentration of liquid dentifrices on caries
      progression.
AB  - OBJECTIVE: This randomized clinical trial evaluated the effect of pH and fluoride
      concentration of liquid dentifrices (LD) on caries progression and fluoride
      uptake in the toenails of 2-4-year-old children. MATERIALS AND METHODS:
      Schoolchildren living in a fluoridated area, with (A) or without (I) active
      caries lesions, were randomly allocated into three groups according to the LD
      they would use over 12 months: group 1 (n = 48-A/56-I): 550 MUg fluoride (F)/g,
      pH 4.5; group 2 (n = 56-A/48-I) 1,100 MUg F/g, pH 7.0; and group 3 (n = 52-A/55
      I): 550 MUg F/g, pH 7.0. The number of lesions becoming active/cavities or
      inactive was clinically evaluated by determining progression or regression.
      Additionally, white spot lesions were evaluated by the quantitative light-induced
      fluorescence (QLF) method in 75 children. Toenail fluoride concentration was also
      evaluated. Data were analyzed by ANOVA and followed by Dunn's test or ANCOVA
      followed by Tukey's test (p < 0.05). RESULTS: Caries net increment followed a
      decreasing pattern according to the dentifrice used (G1 < G2 < G3), regardless
      caries activity, but significant differences were detected only for caries
      progression and net increment (G1 < G3) for the caries-active group when
      evaluated through visual inspection. For the regression, the values found for the
      three groups were more similar, without significant differences. QLF analysis
      detected no significant difference between groups 1 and 2, but they performed
      significantly better than group 3. A significantly lower toenail fluoride
      concentration was observed when children used the low-fluoride dentifrices.
      CONCLUSION: The low-fluoride acidic LD has good potential to prevent caries and
      reduce fluoride intake. CLINICAL RELEVANCE: The low-F acidic dentifrice combines
      the desirable characteristics of caries prevention and reduced fluoride intake
      for a product to be used by children, regardless their caries status.

PMID- 23873320
TI  - The effect of radiotherapy on dental hard tissue--a systematic review.
AB  - INTRODUCTION: Decay of teeth, erosion and disintegration of hard dental tissue
      are a clinically often seen side effect after radiotherapy for tumours in the
      head and neck region. To investigate if these side effects are due to structural
      changes in dental hard tissues, the current literature was searched. It can
      influence the quality of life gravely. METHOD: A systematic PubMed (Medline)
      search was done and of the 374 hits, 11 articles were included. During the
      reading of these articles, 10 additional useful references to other articles were
      retrieved. An extra search was done on "A.M. Kielbassa", a key writer in many
      articles on this subject. Four extra articles were found. So in total, 25
      articles were analysed in this systematic review. RESULTS: Tooth destruction
      occurs often and soon after irradiation. There is no difference between decay in
      irradiated and non-irradiated teeth. The locations and the progressiveness of the
      destruction are different in irradiated then in non-irradiated teeth. Several
      studies show changes in the structure and micro hardness of enamel, the
      dentinoenamel junction (DEJ) and dentin. The biomechanical properties are
      dramatically decreased. The odds of moderate/severe tooth damage increased with
      the irradiation dose. CONCLUSION: In conclusion the results of this systematic
      review show a great amount of changes and damages at all levels of the hard
      dental tissues, enamel, DEJ and dentin. These findings substantiate the idea that
      the formation of recurrent and atypical patterns of dental caries in irradiated
      teeth is, not only due to loss of saliva but a combination of both hyposalivation
      and the direct effects on hard dental tissue. The formation of atypical caries is
      furthermore increased due to poor oral hygiene, the increase of soft and
      carbohydrate-rich substance and changes of the bacterial micro flora and
      proteins. CLINICAL RELEVANCE: This article is written to understand more about
      the cause of destruction of teeth after radiotherapy. This way, a more adequate
      preventive and restorative treatment plan can be drawn up for an individual
      patient.

PMID- 23873321
TI  - Assessment of smoking behaviour in a dental setting: a 1-year follow-up study
      using self-reported questionnaire data and exhaled carbon monoxide levels.
AB  - OBJECTIVES: This study analyses the changes in smoking habits over the course of
      1 year in a group of patients referred to an oral medicine unit. MATERIALS AND
      METHODS: Smoking history and behaviour were analysed at baseline and after 1 year
      based on a self-reported questionnaire and on exhaled carbon monoxide levels [in
      parts per million (ppm)]. During the initial examination, all smokers underwent
      tobacco use prevention and cessation counselling. RESULTS: Of the initial group
      of 121 patients, 98 were examined at the follow-up visit. At the baseline
      examination, 33 patients (33.67 %) indicated that they were current smokers. One
      year later, 14 patients (42.24 % out of the 33 smokers of the initial
      examination) indicated that they had attempted to stop smoking at least once over
      the follow-up period and 15.15 % (5 patients) had quit smoking. The mean number
      of cigarettes smoked per day by current smokers decreased from 13.10 to 12.18 (p
      = 0.04). The exhaled CO level measurements showed very good correlation with a
      Spearman's coefficient 0.9880 for the initial visit, and 0.9909 for the follow-up
      examination. For current smokers, the consumption of one additional cigarette per
      day elevated the CO measurements by 0.77 ppm (p < 0.0001) at the baseline
      examination and by 0.84 ppm (p < 0.0001) at the 1-year follow-up. CONCLUSIONS: In
      oral health care, where smoking cessation is an important aspect of the treatment
      strategy, the measurement of exhaled carbon monoxide shows a very good
      correlation with a self-reported smoking habit. CLINICAL RELEVANCE: Measurement
      of exhaled carbon monoxide is a non-invasive, simple and objective measurement
      technique for documenting and monitoring smoking cessation and reduction.

PMID- 23873322
TI  - Do chlorhexidine and ethanol improve bond strength and durability of adhesion of
      fiber posts inside the root canal?
AB  - OBJECTIVES: The aim was to investigate the effects of chlorhexidine and ethanol
      pretreatment of the root canal on push-out bond strengths and durability of
      adhesion of fiber posts luted with two different adhesive strategies. MATERIALS
      AND METHODS: One hundred twenty human anterior teeth were endodontically treated.
      After post space preparation, the root canals were irrigated using 1 % sodium
      hypochlorite (NaOCl) applied with passive ultrasonic irrigation followed by
      distilled water (control). In pretreatment (PT) group, chlorhexidine (CHX) root
      canals were irrigated using 2 % chlorhexidine; and in the PT group, 99 % ethanol
      was used prior application of the luting agent. Two different post-and-luting
      systems with an etch-and-rinse (CX) adhesive approach (n = 60) and a self
      adhesive resin cement (RX; n = 60) were inserted into the root canals. Bond
      strengths were evaluated initially and after thermocycling and storage for 6
      months using push-out tests. RESULTS: Bond strength was significantly affected by
      the adhesive strategy (p < 0.0005), the pretreatment (p < 0.0005) and the
      location inside the root canal (p < 0.0005; repeated measurement ANOVA). Ethanol
      significantly increased bond strengths irrespective of the luting agent used
      compared to the control and CHX group (p < 0.05; Tukey's B). CONCLUSION: Ethanol
      significantly increased bond strength of the CX and the RX system inside the root
      canal and could be recommended as a final rinse for luting fiber posts using an
      ethanol-based etch-and-rinse adhesive system or self-adhesive resin cement.
      CLINICAL RELEVANCE: PT of the root canal using ethanol seems to facilitate
      adhesive luting of fiber posts with the tested adhesive system and luting
      cements.

PMID- 23873323
TI  - Imaging of mandible invasion by oral squamous cell carcinoma using computed
      tomography, cone-beam computed tomography and bone scintigraphy with SPECT.
AB  - OBJECTIVES: The objective of this paper is to evaluate the predictability of
      preoperative tumour bone invasion of the mandible by squamous cell carcinoma of
      the oral cavity using CT, cone-beam CT and bone scintigraphy with SPECT. MATERIAL
      AND METHODS: Eighty-four patients who had received CT, SPECT or cone-beam
      computed tomography (CBCT), as well as a further 48 patients who undergone all
      these investigations for preoperative evaluation of bone invasion were included
      in the study. A case-control analysis and the receiver operating characteristics
      were performed. Histological results of bone specimens served as the gold
      standard for assessment of bone invasion. RESULTS: CBCT and SPECT showed a
      comparable sensitivity for bone invasion (93 % [CI 0.816-0.972] and 96 % [CI
      0.867-0.990], respectively) which was significantly higher than that of CT (63 %
      [CI 0.488-0.752]). Further, CBCT obtained higher specificity than SPECT (62 % [CI
      0.478-0.743] and 48 % [CI 0.342-0.614], respectively), whereas CT showed the best
      specificity among the investigation methods (81 % [CI 0.677-0.896]). CONCLUSIONS:
      CT scan provides by its high specificity and positive predictive value a precise
      imaging technique for clinical routine. However, CBCT shows a much higher
      sensitivity for cortical bone invasion and a better negative predictive value.
      With a significantly lower exposure dose it can rule out this invasion
      effectively and prevent overtreatment. CLINICAL RELEVANCE: Considering the high
      resolution images delivered by CBCT along with minimized artefacts in the
      mandible it provides an alternative imaging technique, which could be combined
      and accomplished with another soft-tissue imaging modality like MRI to obtain
      optimal hard and soft-tissue visualisation in patients with squamous cell
      carcinoma of the oral cavity.

PMID- 23873324
TI  - Longevity of composite restorations in patients with early childhood caries
      (ECC).
AB  - OBJECTIVES: The aim of this retrospective study was to describe the type and
      extent of composite fillings in a high risk pediatric caries population and
      analyze restoration survival probability in relation to severity of decay, Black
      classification, and composite type. MATERIALS AND METHODS: A total of 1,017
      fillings in 855 primary teeth performed under general anesthesia from 2004-2007
      were included into this study. All 157 patients had early childhood caries after
      the classification of Wyne and were recalled for at least 6 months. A total etch
      adhesive system, in combination with flowable and/or packable composites, was
      used. Failures were evaluated according to clinical criteria. Survival
      probability was calculated using Kaplan-Meier survival analysis. RESULTS: The
      mean observation period for restorations was 30.9 months, with a success rate of
      81.5 %. In 125 cases, restorations failed after an average retention time of 23.6
      months, resulting in an annual failure rate of 4.2 %. The reasons for failure
      were fracture or partial failure (9.6 %), secondary caries (44 %), or complete
      restoration loss (46.4 %). Fillings in patients with severe decay had
      significantly lower survival probabilities. No significant differences were found
      between flowable and packable composites. CONCLUSIONS: Composite fillings are a
      long lasting, high-quality treatment option in pediatric patients with a high
      risk of caries who are treated under general anesthesia. A strict caries
      prevention regimen should be followed to minimize the loss of restorations caused
      by secondary caries. CLINICAL RELEVANCE: Composite fillings are a long lasting,
      high-quality treatment option in children with early childhood caries treated
      under general anesthesia.

PMID- 23873325
TI  - Efficacy of various side-to-side toothbrushes for noncontact biofilm removal.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of four different
      powered toothbrushes with side-to-side action for noncontact biofilm removal in
      vitro. MATERIALS AND METHODS: A three-species biofilm was formed in vitro on
      protein-coated titanium disks using a flow chamber combined with a static biofilm
      growth model. Subsequently, the biofilm-coated substrates were exposed to four
      different side-to-side toothbrushes (A, B, C, and D) with various brushing times
      (2, 4, and 6 s) and brushing (bristle-to-disk) distances (0, 2, and 4 mm). The
      biofilm volumes were measured using volumetric analyses with confocal laser
      scanning microscope images and Imaris version 7.5.2 software. RESULTS: The median
      percentages of biofilm reduction by the analyzed toothbrushes ranged from 9 % to
      80 %. The abilities of the tested toothbrushes to remove the in vitro biofilm
      differed significantly (p < 0.05). Two of the tested toothbrushes (C and D) were
      capable of significant biofilm reduction by noncontact brushing. CONCLUSIONS: It
      was possible to reduce a three-species in vitro biofilm by noncontact brushing
      with two out of four side-to-side toothbrushes. CLINICAL RELEVANCE: Toothbrushes
      C and D show in vitro a high efficacy in biofilm removal without bristle contact.

PMID- 23873326
TI  - A prospective 8-year follow-up of posterior resin composite restorations in
      permanent teeth of children and adolescents in Public Dental Health Service:
      reasons for replacement.
AB  - OBJECTIVES: The aim of the study was to investigate reasons for replacement and
      repair of posterior resin composite (RC) restorations placed in permanent teeth
      of children and adolescents attending Public Dental Health Service in Denmark.
      MATERIAL AND METHOD: All posterior RC placed consecutively by 115 dentists over a
      period of 4 years were evaluated at baseline and up to 8 years later. The
      endpoint of each restoration was defined when repair or replacement was
      performed. The influence of patient, dentist and material factors on reasons for
      repair or replacement was investigated. RESULTS: A total of 4,355 restorations
      were placed. Replacements comprised 406 and repairs 125 restorations. The
      cumulative survival rate at 8 years was 84 %. Failed restorations were most
      frequently seen due to secondary caries (57 %), post-operative sensitivity (POS)
      (10 %) and RC fracture (6 %). POS was observed in 1.5 % of the evaluations and
      reported more often in girls and from teeth restored with a base material. Older
      dentists showed lower proportion of replaced restorations due to secondary caries
      than younger dentists. CONCLUSION: Posterior RC restorations in children and
      adolescents performed in general practice showed a good durability with annual
      failure rates of 2 %. The main reason for failure was secondary caries followed
      by post-operative sensitivity and resin composite fracture. A high proportion of
      replaced/repaired RC restorations were caused by primary caries in a non-filled
      surface. CLINICAL RELEVANCE: Secondary caries was the main reason for failure of
      RC in children and young adults. More teeth with post-operative sensitivity and a
      shorter longevity of restorations were observed when a base material was used.

PMID- 23873327
TI  - Impact of ranolazine on clinical outcomes and healthcare resource utilization in
      patients with refractory angina pectoris.
AB  - BACKGROUND: Ranolazine is a novel antianginal medication approved for the
      treatment of chronic angina. There are only limited data concerning the efficacy
      of ranolazine in reducing healthcare resource utilization in patients with
      refractory angina pectoris. OBJECTIVE: The primary objective of this analysis was
      to evaluate the efficacy and safety of ranolazine in refractory angina pectoris.
      In addition, the impact of ranolazine on healthcare resource utilization was
      assessed. METHODS: Consecutive patients with refractory angina pectoris treated
      with ranolazine at two cardiology practices in the state of Nebraska were
      included in this analysis. The Canadian Cardiovascular Society (CCS) angina class
      and frequency and type of healthcare resource consumption were determined during
      the 12 months prior to and the 12 months after initiation of ranolazine. RESULTS:
      A total of 150 pts (64 % men) with a mean age of 66 +/- 12 years were included in
      this analysis. All patients had previously undergone coronary revascularization.
      Nitrates, beta-adrenoceptor antagonists (beta-blockers), and calcium antagonists
      (calcium channel blockers) were being used in 83, 97, and 75 % of patients,
      respectively. During ranolazine treatment, a significant improvement in CCS
      angina class was observed, with 23 patients improving by one class and no patient
      experiencing a deterioration in functional class (p = 0.025). A total of 53 side
      effects occurred in 28 (19 %) patients receiving ranolazine. Of those patients
      with side effects, four required dose reduction and seven required drug
      discontinuation. The frequency of clinic visits and emergency room visits was
      lower during ranolazine treatment, but the differences in frequency were not
      significant. The number of patients hospitalized and the number of
      hospitalizations were significantly lower during ranolazine therapy than in the
      pre-ranolazine study period (p = 0.002). CONCLUSION: Ranolazine improved the CCS
      angina class and reduced hospitalizations over a 12-month follow-up period in a
      group of patients with difficult-to-treat refractory angina pectoris.

PMID- 23873328
TI  - Development of metabolic syndrome and electrocardiographic features of left
      ventricular hypertrophy in middle-aged working subjects.
AB  - BACKGROUND AND AIMS: Metabolic syndrome (MS) leads to excess cardiovascular
      disease, including heart failure. Left ventricular hypertrophy (LVH) is common in
      MS patients, but it is unknown whether onsets of MS and LVH coincide. Herein, we
      tested the association between development of MS and of electrocardiographic LVH
      in a cohort of middle-aged individuals. METHODS: We included 303 working subjects
      (mean age 43.0 +/- 6.2; 41% males), followed- up for 4.3 +/- 0.8 yr. ATP-III MS
      components were determined. Electrocardiographic LVH features were assessed by
      Sokolow and Cornell voltage indexes and Romhilt-Estes (RE) score. RESULTS: At
      baseline, Cornell index was significantly higher in subjects with (no.=55; 18.2%)
      than in those without MS (12.8 +/- 6.4 vs 10.9 +/- 5.4 mm; p=0.023), while
      Sokolow index and RE score were not different. At followup, individuals who
      developed (no.=51) compared to those who did not develop MS showed a significant
      increase in Cornell voltage index (1.0 +/- 0.6 vs -0.55 +/- 0.3 mm; p=0.035) and
      RE score (0.17 +/- 0.17 vs -0.08 +/- 0.04; p=0.028). The change in Cornell index
      over time was directly correlated with the change in the number of MS components
      (r=0.133; p=0.02) and in homeostasis model assessment of insulin resistance
      (r=0.117; p=0.046). The association between MS onset and the increase in Cornell
      index/RE score was independent from confounders. CONCLUSIONS: In a young
      population of working subjects, the development of MS is associated with
      worsening features of LVH. Early LVH electrocardiographic screening in young
      subjects who develop MS should be considered and performed using Cornell voltage
      index.

PMID- 23873329
TI  - Characteristics of cerebrovascular accidents at time of diagnosis in a series of
      98 patients with giant cell arteritis.
AB  - The objective of this study was to determine the characteristics of
      cerebrovascular accidents at time of diagnosis in patients with giant cell
      arteritis. Retrospective data were collected from 98 patients at a single
      hospital with giant cell arteritis (according to the American College of
      Rheumatology classification criteria) diagnosed between October 1999 and January
      2012. Cerebrovascular accident was found at initial presentation in 6 patients
      (6.1 %, 95 % CIs 2.3-12.9). Most of them had other symptoms of giant cell
      arteritis when the disease began. Signs reflecting the involvement of vertebro
      basilar territory were present in 3 cases. No other case of cerebrovascular
      accident was described during the follow-up of patient; particularly no case of
      cerebrovascular accident occurred once corticosteroid therapy for the treatment
      of giant cell arteritis had been initiated. No differences in the epidemiologic,
      clinical and laboratory features at the time of diagnosis between patients who
      had cerebrovascular accidents and the rest of the giant cell arteritis patients
      were observed. Prognosis was good in our survey. However, there was no case of
      bilateral vertebral artery occlusion, a condition associated with poor prognosis.
      The present study confirms that cerebrovascular accidents may be the initial
      manifestation of giant cell arteritis, an argument in favor of a direct effect of
      the vasculitis in the development of cerebrovascular accidents rather than a
      complication of the corticosteroid therapy. The diagnosis of giant cell arteritis
      should always be considered in an elderly patient with stroke and an unexplained
      elevation of inflammatory biomarkers.

PMID- 23873330
TI  - Thalamic input to representations of the teeth, tongue, and face in somatosensory
      area 3b of macaque monkeys.
AB  - Representations of the parts of the oral cavity and face in somatosensory area 3b
      of macaque monkeys were identified with microelectrode recordings and injected
      with different neuroanatomical tracers to reveal patterns of thalamic projections
      to tongue, teeth, and other representations in primary somatosensory cortex. The
      locations of injection sites and resulting labeled neurons were further
      determined by relating sections processed to reveal tracers to those processed
      for myeloarchitecture in the cortex and multiple architectural stains in the
      thalamus. The ventroposterior medial subnucleus (VPM) for touch was identified as
      separate from the ventroposterior medial parvicellular nucleus (VPMpc) for taste
      by differential expression of several types of proteins. Our results revealed
      somatotopically matched projections from VPM to the part of 3b representing intra
      oral structures and the face. Retrogradely labeled cells resulting from
      injections in area 3b were also found in other thalamic nuclei including:
      anterior pulvinar (Pa), ventroposterior inferior (VPI), ventroposterior superior
      (VPS), ventroposterior lateral (VPL), ventral lateral (VL), center median (CM),
      central lateral (CL), and medial dorsal (MD). None of our injections, including
      those into the representation of the tongue, labeled neurons in VPMpc, the
      thalamic taste nucleus. Thus, area 3b does not appear to be involved in
      processing taste information from the thalamus. This result stands in contrast to
      those reported for New World monkeys.

PMID- 23873331
TI  - Expression of CYP1A1, CYP1B1 and MnSOD in a panel of human cancer cell lines.
AB  - The expression of P450 enzymes and antioxidative enzymes in tumour tissue can
      have a major impact on the responsiveness of tumours to cancer chemotherapeutic
      drugs, therefore such information may be very precious when experiments are
      designed. The compressive information, concerning the expression of drug
      metabolism enzymes or antioxidative enzymes is still lacking, therefore in this
      study the expression of CYP1A1, CYP1B1 and mitochondrial superoxide dismutase
      MnSOD (both mRNA and protein) in a panel of eight commonly used cancer cell
      lines, representing four tumour tissues was assayed. In the study two ovarian
      cancer cell lines A2780 and SKOV-3, two colorectal cancer LOVO and DLD-1, two
      breast cancer derived MCF-7 and MDA-MB-231 and two cervical cancer cell lines
      HeLa and C33A were employed. The relatively high expression of all assayed
      enzymes was shown in MDA-MB-231 breast cancer cells, lack of cancer cell specific
      CYP1B1 protein was discovered in LOVO colorectal cells. In order to test possible
      correlation between expression of CYP1A1, CYP1B1 and MnSOD and modulators of
      their activity, cytotoxicity of resveratrol and its promising hydroxylated
      analogue 3,3',4,4',5,5'-trans-hexahydroxystilbene against cell lines used in
      experiment was assayed. The relatively high correlation was found between IC50
      values calculated for 3,3',4,4',5,5'-trans-hexahydroxystilbene and expression of
      MnSOD (r = 0.6562).

PMID- 23873332
TI  - Concerted inhibition of HIF-1alpha and -2alpha expression markedly suppresses
      angiogenesis in cultured RPE cells.
AB  - HIF-1alpha is known to play an important role in the induction of VEGF by hypoxia
      in retinal pigment epithelial (RPE) cells. However, the involvement of the other
      isoform, HIF-2alpha, in RPE cells remains unclear. Thus, the purpose of present
      study was to clarify the role of HIF-2alpha during induction of angiogenic genes
      in hypoxic RPE cells. When human RPE cells (ARPE-19) were cultured under hypoxic
      conditions, HIF-1alpha and HIF-2alpha proteins increased. This induced an
      increase in mRNA for VEGF, causing secretion of VEGF protein into the medium.
      This conditioned medium induced tube formation in human vascular endothelial
      cells (HUVEC). The increased expression of mRNA for VEGF in hypoxic RPE cells was
      partially inhibited by HIF-1alpha siRNA, but not by HIF-2alpha siRNA. However, co
      transfection of HIF-1alpha siRNA and HIF-2alpha siRNA augmented downregulation of
      VEGF mRNA and protein in hypoxic RPE cells and inhibited formation of tube-like
      structures in HUVEC. GeneChip and PCR array analyses revealed that not only VEGF,
      but also expression of other angiogenic genes were synergistically downregulated
      by co-transfection of hypoxic RPE cells with HIF-1alpha and HIF-2alpha siRNAs.
      These findings suggest an important compensatory role for the HIF-2alpha isoform
      in the regulation of angiogenic gene expression. Thus, suppression of angiogenic
      genes for HIF-1alpha and HIF-2alpha may be a possible therapeutic strategy
      against retinal angiogenesis in Age-related macular degeneration (ARMD).

PMID- 23873334
TI  - B-H activation and H-H formation: two consecutive heterolytic processes on an
      osmium-hydrogensulfide bond.
AB  - Heterolytic B-H activation and H-H formation on an Os-SH bond give borylthiolate
      dihydrogen derivatives. These species exchange borylthiol by borane to afford
      sigma-borane derivatives or release H2 and undergo a hydride-boryl exchange to
      yield boryl-hydrogensulfide complexes depending on the boryl group bonded to the
      sulfur atom. 

PMID- 23873333
TI  - Neuroprotective effect of 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-beta-D
      pyranoside against sodium nitroprusside-induced neurotoxicity in HT22 cells.
AB  - 2-(4-Methoxyphenyl) ethyl-2-acetamido-2-deoxy-beta-D-pyranoside (GlcNAc-Sal), the
      salidroside analog was synthesized and shown to inhibit hypoglycemia and serum
      limitation induced apoptosis in PC12 cells. This study investigated the
      protective effects of GlcNAc-Sal on sodium nitroprusside (SNP)-induced
      cytotoxicity in HT22 cells. Cell viability tests and Hoechst 33342 staining
      comfirmed that GlcNAc-Sal pretreatment attenuated SNP-stimulated apoptotic cell
      death in HT22 cells in a concentration-dependent manner. The measurements of
      reactive oxygen species (ROS), nitric oxide (NO) production and apoptosis-related
      gene and protein expression suggest that the protection of GlcNAc-Sal, shown in
      this study, might be mediated by inhibiting intracellular ROS and NO production,
      and regulating apoptosis-related gene and protein expression during SNP
      stimulation. Perhaps, this study might contribute to the development of GlcNAc
      Sal as an agent for preventing and/or treating a variety of NO-induced brain
      diseases.

PMID- 23873335
TI  - Lithothamnion muelleri controls inflammatory responses, target organ injury and
      lethality associated with graft-versus-host disease in mice.
AB  - Lithothamnion muelleri (Hapalidiaceae) is a marine red alga, which is a member of
      a group of algae with anti-inflammatory, antitumor, and immunomodulatory
      properties. The present study evaluated the effects of treatment with
      Lithothamnion muelleri extract (LM) in a model of acute graft-versus-host disease
      (GVHD), using a model of adoptive splenocyte transfer from C57BL/6 donors into
      B6D2F1 recipient mice. Mice treated with LM showed reduced clinical signs of
      disease and mortality when compared with untreated mice. LM-treated mice had
      reduced tissue injury, less bacterial translocation, and decreased levels of
      proinflammatory cytokines and chemokines (interferon-gamma (IFN-gamma), tumor
      necrosis factor-alpha (TNF-alpha), chemokine (C-C motif) ligand 2 (CCL2),
      chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5)).
      The polysaccharide-rich fraction derived from LM could inhibit leukocyte rolling
      and adhesion in intestinal venules, as assessed by intravital microscopy. LM
      treatment did not impair the beneficial effects of graft-versus-leukaemia (GVL).
      Altogether, our studies suggest that treatment with Lithothamnion muelleri has a
      potential therapeutic application in GVHD treatment. 

PMID- 23873336
TI  - Incidence and aetiology of renal phosphate loss in patients with hypophosphatemia
      in the intensive care unit.
AB  - BACKGROUND: Hypophosphatemia is a common finding in patients in the intensive
      care unit (ICU). Its cause is often poorly understood. PURPOSE: The aim of this
      study was to understand the incidence of renal phosphate loss in ICU-related
      hypophosphatemia, and to examine the role of phosphaturic hormones in its
      etiology. METHODS: Plasma phosphate levels were measured on day 1, 3, 5 and 7 in
      290 consecutive patients admitted to the ICU. Renal phosphate handling and
      phosphaturic hormones were studied in a subset of patients with phosphate levels
      <0.6 mmol/L. Renal phosphate loss was defined as a TmP/gfr < 0.6 mmol/L. MAIN
      RESULTS: Hypophosphatemia developed in 24% of all patients. This mainly occurred
      within the first 3 days of stay and in patients with serum creatinine levels <150
      MUmol/L. Renal phosphate loss was present in 80% of patients who developed
      hypophosphatemia, and was not related to serum levels of parathyroid hormone
      (PTH), PTH-related protein (PTH-rp), fibroblast growth factor 23 (FGF-23), or
      calcitonin. CONCLUSION: Hypophosphatemia in the ICU is commonly associated with
      renal phosphate loss. It mainly occurs within the first 3 days of admission, in
      particular in patients with preserved renal function. Renal phosphate loss is not
      explained by elevated PTH, PTH-rp, FGF-23 or calcitonin levels.

PMID- 23873337
TI  - Risk of functional impairment in Facioscapulohumeral muscular dystrophy.
AB  - INTRODUCTION: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most
      prevalent muscular dystrophies. Nevertheless, little is known about the risk of
      developing functional impairment. Here we determine the 6-year risk of functional
      impairment in FSHD. METHODS: A retrospective cohort of 313 genetically confirmed,
      clinically affected FSHD participants in a United States registry between January
      2002 and June 2011. Our main outcome was wheelchair (WC) use. RESULTS: The 6-year
      risk of WC use was 24.0% (95% confidence interval 18.6-29.3). The distribution of
      WC risk was bimodal, with a peak in the second decade associated with large D4Z4
      contractions, followed by an age-related increase in risk. Other functional
      categories showed moderate risk. Prevalence of hearing aid use and difficulty
      pronouncing words was increased in large D4Z4 contractions. CONCLUSIONS: The 6
      year risk of functional impairment in FSHD is moderate, and early WC use is
      associated with large D4Z4 contractions.

PMID- 23873338
TI  - Factors associated with amplified HIV transmission behavior among American men
      who have sex with men engaged in care: implications for clinical providers.
AB  - BACKGROUND: The HIV epidemic continues unabated in the USA, with men who have sex
      with men (MSM) being most frequently infected. PURPOSE: The purpose of this study
      is to understand the biological and behavioral risk factors associated with
      increased HIV transmission efficiency, which is HIV transmission risk behavior in
      the context of uncontrolled HIV replication or intercurrent sexually transmitted
      infections. METHODS: Participants were 201 HIV-infected MSM who received their
      primary care at an HIV ambulatory care center in Boston. Logistic regression
      models were conducted to determine factors associated with engaging in behavior
      associated with potentially amplified transmission. RESULTS: In the final model,
      heavy alcohol use (AOR, 3.27; 95 % CI 1.37-7.79), as well as stimulant drug use
      (crystal meth, crack, or other cocaine; AOR, 3.00; CI 1.32-6.84), having at least
      a college degree (OR, 2.74; CI, 1.15-6.54), and decreased duration of HIV
      infection (OR, 0.91; CI, 0.85-0.97) were each uniquely associated with enhanced
      HIV transmission behavior. CONCLUSIONS: HIV primary care providers should
      routinely assess patients for potential HIV transmission behaviors, particularly
      those who are younger and more recently diagnosed with HIV, who drink alcohol
      heavily, and who use any nonprescription drugs, particularly stimulants, in order
      to decrease the spread of HIV.

PMID- 23873339
TI  - Effect of cryotherapy on muscle recovery and inflammation following a bout of
      damaging exercise.
AB  - The purpose of this study was to determine the effect of cryotherapy on the
      inflammatory response to muscle-damaging exercise using a randomized trial.
      Twenty recreationally active males completed a 40-min run at a -10 % grade to
      induce muscle damage. Ten of the subjects were immersed in a 5  degrees C ice
      bath for 20 min and the other ten served as controls. Knee extensor peak torque,
      soreness rating, and thigh circumference were obtained pre- and post-run, and 1,
      6, 24, 48, and 72 h post-run. Blood samples were obtained pre- and post-run, and
      1, 6 and 24 h post-run for assay of plasma chemokine ligand 2 (CCL2). Peak torque
      decreased from 270 +/- 57 Nm at baseline to 253 +/- 65 Nm post-run and increased
      to 295 +/- 68 Nm by 72 h post-run with no differences between groups (p = 0.491).
      Soreness rating increased from 3.6 +/- 6.0 mm out of 100 mm at baseline to 47.4
      +/- 28.2 mm post-run and remained elevated at all time points with no differences
      between groups (p = 0.696). CCL2 concentrations increased from 116 +/- 31 pg mL(
      1) at baseline to 293 +/- 109 pg mL(-1) at 6 h post-run (control) and from 100 +/
      27 pg mL(-1) at baseline to 208 +/- 71 pg mL(-1) at 6 h post-run (cryotherapy).
      The difference between groups was not significant (p = 0.116), but there was a
      trend for lower CCL2 in the cryotherapy group at 6 h (p = 0.102), though this
      measure was highly variable. In conclusion, 20 min of cryotherapy was ineffective
      in attenuating the strength decrement and soreness seen after muscle-damaging
      exercise, but may have mitigated the rise in plasma CCL2 concentration. These
      results do not support the use of cryotherapy during recovery. 

PMID- 23873340
TI  - Structural characterization and thermal and chemical stability of bioactive
      molecule-hydrotalcite (LDH) nanocomposites.
AB  - Layered double hydroxides (LDH) are versatile materials used for intercalating
      bioactive molecules, both in pharmaceutical and cosmetic fields, with the purpose
      of protecting them from degradation, enhancing their water solubility to increase
      bioavailability, and/or obtaining modified release properties. The properties of
      the intercalation compounds of Mg/Al_LDH and Zn/Al_LDH with different drugs and
      sunscreens, namely diclofenac, ketoprofen, gliclazide, retinoic acid, furosemide,
      para-aminobenzoic acid and 2-phenylbenzimidazolsulfonic (Eusolex) acid, have been
      studied by crystallographic, spectroscopic and thermogravimetric techniques and
      by solid state NMR, to shed light on their structure, their molecular
      interactions and their stability from the thermal and chemical viewpoint. The
      structural features were described with particular attention to the interaction
      between the organic and inorganic components and to the stability of the
      intercalation products. For the first time two synchrotron radiation powder
      diffraction patterns of organic-containing LDH were solved and refined by
      Rietveld methods to obtain an experimental crystal structure. 

PMID- 23873341
TI  - Continuous positive airway pressure and cardiovascular events in patients with
      obstructive sleep apnea.
AB  - The obstructive sleep apnea syndrome (OSAS) is associated with the
      development/worsening of cardiovascular disease. OSAS is considered to be an
      independent risk factor for hypertension and is linked to increased mortality in
      the context of coronary heart disease, the development of cardiac arrhythmias and
      increased risk of developing mild pulmonary hypertension. OSAS is also associated
      with cerebrovascular mortality and morbidity. In heart failure, OSAS can lead to
      worsening of symptoms. Treatment of OSAS using positive airways pressure therapy
      (PAP) has been shown in randomized, controlled trials in selected populations to
      reduce some, but not all of these cardiovascular and cerebrovascular risks.
      Unequivocal evidence of causality for OSAS in the development, progression, and
      outcomes of these disorders in all individuals suffering from them, is lacking.
      Good quality long-term morbidity and mortality data for the effects of OSAS on
      cardiometabolic health and the impact of PAP treatment are likewise limited. 

PMID- 23873342
TI  - Rare-earth-doped biological composites as in vivo shortwave infrared reporters.
AB  - The extension of in vivo optical imaging for disease screening and image-guided
      surgical interventions requires brightly emitting, tissue-specific materials that
      optically transmit through living tissue and can be imaged with portable systems
      that display data in real-time. Recent work suggests that a new window across the
      short-wavelength infrared region can improve in vivo imaging sensitivity over
      near infrared light. Here we report on the first evidence of multispectral, real
      time short-wavelength infrared imaging offering anatomical resolution using
      brightly emitting rare-earth nanomaterials and demonstrate their applicability
      toward disease-targeted imaging. Inorganic-protein nanocomposites of rare-earth
      nanomaterials with human serum albumin facilitated systemic biodistribution of
      the rare-earth nanomaterials resulting in the increased accumulation and
      retention in tumour tissue that was visualized by the localized enhancement of
      infrared signal intensity. Our findings lay the groundwork for a new generation
      of versatile, biomedical nanomaterials that can advance disease monitoring based
      on a pioneering infrared imaging technique. 

PMID- 23873344
TI  - Be squared: expanding the horizon of squaric acid-mediated conjugations.
AB  - Squaric acid diesters can be applied as reagents to couple two amino-functional
      compounds. Consecutive coupling of two amines allows the synthesis of asymmetric
      squaric acid bisamides with either low molecular weight compounds but also
      biomolecules or polymers. The key feature of the squaric acid diester mediated
      coupling is the reduced reactivity of the resulting ester-amide after the first
      amidation step of the diester. This allows the sequential amidation and
      generation of asymmetric squaramides with high selectivity and in high yields.
      This article gives an overview of the well-established squaric acid diester
      mediated coupling reactions for glycoconjugates and presents recent advances that
      aim to expand this very versatile reaction protocol to the modification of
      peptides and proteins. 

PMID- 23873343
TI  - Retroviruses facilitate the rapid evolution of the mammalian placenta.
AB  - The mammalian placenta exhibits elevated expression of endogenous retroviruses
      (ERVs), but the evolutionary significance of this feature remains unclear. I
      propose that ERV-mediated regulatory evolution was, and continues to be, an
      important mechanism underlying the evolution of placental development. Many
      recent studies have focused on the co-option of ERV-derived genes for specific
      functional adaptations in the placenta. However, the co-option of ERV-derived
      regulatory elements could potentially lead to the incorporation of entire gene
      regulatory networks, which, I argue, would facilitate relatively rapid
      developmental evolution of the placenta. I suggest a model in which an ancient
      retroviral infection led to the establishment of the ancestral placental
      developmental gene network through the co-option of ERV-derived regulatory
      elements. Consequently, placental development would require elevated tolerance to
      ERV activity. This in turn would expose a continuous stream of novel ERV
      mutations that may have catalyzed the developmental diversification of the
      mammalian placenta.

PMID- 23873345
TI  - Evaluation of the morphological variations of the meniscus: a cadaver study.
AB  - PURPOSE: The purpose of this study was to reveal the prevalence of the subtypes
      of the meniscus using human cadaver knees. METHODS: Four hundred and thirty-seven
      cadaveric knees in 219 subjects (formalin fixed, Japanese population) with a
      median age of 83 years (54-97) were included in this study. All soft tissues
      surrounding the knee, excluding the meniscus, were resected, and macroscopic
      assessment of the meniscus was performed. Meniscus subtypes were classified as:
      (1) normal meniscus, (2) complete discoid, (3) incomplete discoid, (4) ring
      shaped, and (5) double-layered. RESULTS: All subtypes of the meniscus were
      observed in the lateral meniscus. Complete discoid lateral meniscus was observed
      in 27 knees (6.2%), incomplete discoid lateral meniscus was observed in 139 knees
      (31.8%), ring-shaped lateral meniscus was observed in 4 knees (0.9%), and double
      layered meniscus was observed in 2 knees (0.5%). CONCLUSION: This study reports
      the accurate prevalence of ring-shaped and double-layered meniscus. None of the
      subtypes were detected in the medial meniscus in this study. For clinical
      relevance, the results of this study can be useful in assisting the diagnosis of
      meniscus tear in clinical situations.

PMID- 23873346
TI  - The gut-liver axis.
AB  - PURPOSE OF REVIEW: The liver adaptively responds to extra-intestinal and
      intestinal inflammation. In recent years, the role of the autonomic nervous
      system, intestinal failure and gut microbiota has been investigated in the
      development of hepatic, intestinal and extra-intestinal disease. RECENT FINDINGS:
      The autonomic nervous system can be stimulated via enteral fat leading to
      cholecystokinin release, stimulating receptors in the gut and in the brain. This
      promotes bowel integrity, dampening the inflammatory response to food antigens.
      Consensus exists that intravenously administered long-chain fatty acids can cause
      liver damage but randomized-controlled trials are lacking. Disruption of the
      enterohepatic circulation of bile salts can give rise to cholestasis and
      nonalcoholic fatty liver disease, which may progress to fibrosis and cirrhosis.
      Reduced intestinal availability of bile salts reduces stimulation of the
      farnesoid X receptor. This may induce hepatic bile salt overload and associated
      hepatotoxicity through reduced action of intestinal fibroblast growth factor 19.
      Evidence is put forward to suggest that the intestinal microbiota is associated
      with liver abnormalities. SUMMARY: Enteral lipids reduce inflammation and liver
      damage during stress or systemic inflammation, whereas parenteral lipid is
      associated with liver damage. Maintaining the enterohepatic circulation of bile
      salts limits hepatic cholestasis through an farnesoid X receptor feedback
      pathway. Changes in gut microbiota composition may induce liver disease.

PMID- 23873347
TI  - High shear rheology and anisotropy in concentrated solutions of monoclonal
      antibodies.
AB  - The high shear rheology of three concentrated solutions of immunoglobulin G1
      monoclonal antibodies (mAb1, mAb2, and mAb3), differing only in their
      complementarity determining regions, was characterized using rotary and capillary
      rheometry. The more viscous solutions (mAb1 and mAb3) showed non-Newtonian
      behavior at high shear rates exhibiting both shear thinning and appreciable
      normal stress differences (NSDs) in the shear rate range gamma = 10 to 10(4) s(
      1) . The rheograms were retraced after gamma is increased and decreased,
      suggesting reversible self-associations under shear. In contrast, mAb2 solutions
      showed Newtonian behavior up to gamma = 6 * 10(4) s(-1) . The critical shear
      stress tauc , corresponding to the onset of the reduction in the viscosity eta,
      is a measure of mAb equilibrium cluster strength and increased rapidly with
      concentration for the high viscosity mAb solutions above 100 mg/mL. In addition,
      decreasing the temperature from 20 degrees C to 5 degrees C increased eta at low
      gamma, but shear-thinning was enhanced and its onset occurred at a lower gammac .
      Using an Arrhenius model eta = A exp(Ea /kT), the activation energy for viscous
      flow Ea was found to decrease for mAb1 solutions as gamma was increased from 10
      to 10(4) s(-1) , suggesting mAb cluster disruption or rearrangement under shear.
      In contrast, for mAb2, this Ea remained constant in the gamma range. Finally,
      mAb1 and mAb3 solutions showed appreciable NSDs, with their N1 > 0 scaling
      linearly with gamma in the range 10(3) to 10(4) s(-1) , whereas their |N2 /N1 |
      was less than 0.25 in this region. These suggest anisotropy and deformation of
      their solution microstructure toward the extensional quadrant of the flow at high
      gamma. In contrast, the NSDs for mAb2 were close to zero indicating that the
      solution microstructure under shear is practically isotropic.

PMID- 23873348
TI  - Chemical structure, biosynthesis and synthesis of free and glycosylated
      pyridinolines formed by cross-link of bone and synovium collagen.
AB  - This review focuses on the chemical structure, biosynthesis and synthesis of free
      and glycosylated pyridinolines (Pyds), fluorescent collagen cross-links, with a
      pyridinium salt structure. Pyds derive from the degradation of bone collagen and
      have attracted attention for their use as biochemical markers of bone resorption
      and to assess fracture risk prediction in persons suffering from osteoporosis,
      bone cancer and other bone or collagen diseases. We consider and critically
      discuss all reported syntheses of free and glycosylated Pyds evidencing an
      unrevised chemistry, original and of general utility, analysis of which allows us
      to also support a previously suggested non-enzymatic formation of Pyds in
      collagen better rationalizing and justifying the chemical events. 

PMID- 23873349
TI  - Ruthenium nanocrystals as cathode catalysts for lithium-oxygen batteries with a
      superior performance.
AB  - The key factor to improve the electrochemical performance of Li-O2 batteries is
      to find effective cathode catalysts to promote the oxygen reduction and oxygen
      evolution reactions. Herein, we report the synthesis of an effective cathode
      catalyst of ruthenium nanocrystals supported on carbon black substrate by a
      surfactant assisting method. The as-prepared ruthenium nanocrystals exhibited an
      excellent catalytic activity as cathodes in Li-O2 batteries with a high
      reversible capacity of about 9,800 mAh g-1, a low charge-discharge over-potential
      (about 0.37 V), and an outstanding cycle performance up to 150 cycles (with a
      curtaining capacity of 1,000 mAh g-1). The electrochemical testing shows that
      ruthenium nanocrystals can significantly reduce the charge potential comparing to
      carbon black catalysts, which demonstrated that ruthenium based nanomaterials
      could be effective cathode catalysts for high performance lithium- O2 batteries.

PMID- 23873350
TI  - Methods for quantification of pore-voltage sensor interaction in Ca(V)1.2.
AB  - Voltage sensors (VSs) initiate the pore opening and closure in voltage-gated ion
      channels. Here, we propose a technique for estimation of the equilibrium constant
      of the up- and downward VS movements and rate constants of pore transitions from
      macroscopic current kinetics. Bell-shaped voltage dependence of the
      activation/deactivation time constants and Bolzmann distributions of CaV1.2
      activation were analyzed in terms of a circular four-state (rest, activated,
      open, deactivated) channel model: both dependencies uniquely constrain the model
      parameters. Neutralization of gating charges in IS4 or IIS4 only slightly affects
      the equilibrium constant of VS transition while affecting simultaneously the rate
      constants of pore opening and closure. The application of our technique revealed
      that pore mutations on IS6-IVS6 segments induce pronounced shifts of the VS
      equilibrium between the resting (down) and activated (up) position. Analyzing a
      channelopathy mutation highlighted that the leftward shift of the activation
      curve induced by I781T on IIS6 is only partially (35 %) caused by a
      destabilization of the channel pore but predominantly (65 %) by a shifted VS
      equilibrium towards activation. The algorithm proposed for CaV1.2 may be
      applicable for calculating rate constants from macroscopic current kinetics in
      other voltage-gated ion channels. 

PMID- 23873351
TI  - The bundle crossing region is responsible for the inwardly rectifying internal
      spermine block of the Kir2.1 channel.
AB  - Inward rectifier potassium channels conduct K(+) across the cell membrane more
      efficiently in the inward than outward direction in physiological conditions.
      Voltage-dependent and flow-dependent blocks of outward K(+) currents by
      intracellular polyamines (e.g., spermine (SPM)) have been proposed as the major
      mechanisms underlying inward rectification. In this study, we show that the SPM
      blocking affinity curve is shifted according to the shift in K(+) reversal
      potential. Moreover, the kinetics of SPM entry to and exit from the binding site
      are correlatively slowed by specific E224 and E299 mutations, which always also
      disrupt the flux coupling feature of SPM block. The entry rates carry little
      voltage dependence, whereas the exit rates are e-fold decelerated per ~15 mV
      depolarization. Interestingly, the voltage dependence remains rather constant
      among WT and quite a few different mutant channels. This voltage dependence
      offers an unprecedented chance of mapping the location (electrical distance) of
      the SPM site in the pore because these kinetic data were obtained along the
      preponderant direction of K(+) current flow (outward currents for the entry rate
      and inward currents for the exit rate) and thus contamination from flow
      dependence should be negligible. Moreover, double mutations involving E224 and
      A178 or M183 seem to alter the height of the same asymmetrical barrier between
      the SPM binding site and the intracellular milieu. We conclude that the SPM site
      responsible for the inward rectifying block is located at an electrical distance
      of ~0.5 from the inside and is involved in a flux coupling segment in the bundle
      crossing region of the pore. With preponderant outward K(+) flow, SPM is "pushed"
      to the outmost site of this segment (~D172). On the other hand, the blocking SPM
      would be pushed to the inner end of this segment (~M183-A184) with preponderant
      inward K(+) flow. Moreover, E224 and E299 very likely electrostatically interact
      with the other residues (e.g., R228, R260) in the cytoplasmic domain and then
      allosterically keep the bundle crossing region in an open conformation
      appropriate for the flux coupling block of SPM.

PMID- 23873352
TI  - Acidosis prevents and alkalosis augments endothelium-dependent contractions in
      mouse arteries.
AB  - Changes in pH modulate the responsiveness of vascular smooth muscle cells to
      vasoconstrictor stimuli, but their effect on endothelium-dependent responses is
      unknown. Therefore, the influence of moderate changes in pH on responses to
      endothelium-dependent and -independent agonists was determined in aortae and
      carotid arteries of 15- to 26-week-old male C57BL/6N mice. Isolated rings were
      suspended in Halpern-Mulvany myographs for isometric tension recording. The
      preparations were exposed to either acidic (pH 7), control (pH 7.4) or alkaline
      (pH 7.8) modified Krebs-Ringer bicarbonate buffer solutions and their
      contractions and relaxations compared. Endothelium-dependent relaxations to
      acetylcholine (in the presence of meclofenamate or of the thromboxane-prostanoid
      (TP) receptor antagonist S18886) were comparable at the three pH values tested in
      contracted aortic or carotid arterial rings. Endothelium-dependent contractions
      of quiescent carotid arteries were reduced in acidosis and potentiated in
      alkalosis compared to control; these effects were reversible. The carotid
      arteries produced equal amounts of 6-keto prostaglandin F1alpha and thromboxane
      B2 at the different pH values tested. Contractions to the full TP receptor
      agonist U46619 were similar in the three milieus, but after inducing partial TP
      receptor blockade (with low concentrations of the TP receptor antagonist S18886)
      they were depressed in acidosis compared to alkalosis. Prostacyclin as a partial
      TP receptor activator also induced weaker contractions at low than at high pH,
      whereas its vasodilator effect was not affected. These findings demonstrate that
      changes in pH modulate endothelium-dependent contractions in mouse arteries
      primarily by altering the sensitivity of TP receptors of vascular smooth muscle
      to endothelium-derived contracting factors. 

PMID- 23873353
TI  - Advanced glycation end products impair K(Ca)3.1- and K(Ca)2.3-mediated
      vasodilatation via oxidative stress in rat mesenteric arteries.
AB  - The present study was designed to investigate the role of advanced glycation end
      products (AGEs) in intermediate-conductance and small-conductance Ca(2+)
      activated potassium channels (KCa3.1 and KCa2.3)-mediated relaxation in rat
      resistance arteries and the underlying mechanism. The endothelial function of
      mesenteric arteries was assessed with the use of wire myography. Expression
      levels of KCa3.1 and KCa2.3 were measured by using Western blot. Reactive oxygen
      species (ROS) were measured by using dihydroethidium and 2', 7'
      dichlorofluorescein diacetate. KCa3.1 and KCa2.3-mediated vasodilatation
      responses to acetylcholine and NS309 (opener of KCa3.1 and KCa2.3) were impaired
      by incubation of the third-order mesenteric arteries from normal rats with AGEs
      (200 MUg ml(-1) for 3 h). In cultured human umbilical vein endothelial cells
      (HUVECs), AGEs increased ROS level and decreased the protein expression of KCa3.1
      and KCa2.3. Antioxidant alpha lipoic acid restored the impairment in both
      vasodilatation function and expression of KCa3.1 and KCa2.3. H2O2 could mimic the
      effect of AGEs on the protein expression of KCa3.1 and KCa2.3 in cultured HUVECs.
      These results demonstrate for the first time that AGEs impaired KCa3.1 and KCa2.3
      mediated vasodilatation in rat mesenteric arteries via downregulation of both
      KCa3.1 and KCa2.3, in which the enhanced oxidative stress was involved.

PMID- 23873354
TI  - Genetic deletion of aquaporin-1 results in microcardia and low blood pressure in
      mouse with intact nitric oxide-dependent relaxation, but enhanced prostanoids
      dependent relaxation.
AB  - The water channels, aquaporins (AQPs) are key mediators of transcellular fluid
      transport. However, their expression and role in cardiac tissue is poorly
      characterized. Particularly, AQP1 was suggested to transport other molecules
      (nitric oxide (NO), hydrogen peroxide (H2O2)) with potential major bearing on
      cardiovascular physiology. We therefore examined the expression of all AQPs and
      the phenotype of AQP1 knockout mice (vs. wild-type littermates) under implanted
      telemetry in vivo, as well as endothelium-dependent relaxation in isolated aortas
      and resistance vessels ex vivo. Four aquaporins were expressed in wild-type heart
      tissue (AQP1, AQP7, AQP4, AQP8) and two aquaporins in aortic and mesenteric
      vessels (AQP1-AQP7). AQP1 was expressed in endothelial as well as cardiac and
      vascular muscle cells and co-segregated with caveolin-1. AQP1 knockout (KO) mice
      exhibited a prominent microcardia and decreased myocyte transverse dimensions
      despite no change in capillary density. Both male and female AQP1 KO mice had
      lower mean BP, which was not attributable to altered water balance or autonomic
      dysfunction (from baroreflex and frequency analysis of BP and HR variability). NO
      dependent BP variability was unperturbed. Accordingly, endothelium-derived
      hyperpolarizing factor (EDH(F)) or NO-dependent relaxation were unchanged in
      aorta or resistance vessels ex vivo. However, AQP1 KO mesenteric vessels
      exhibited an increase in endothelial prostanoids-dependent relaxation, together
      with increased expression of COX-2. This enhanced relaxation was abrogated by COX
      inhibition. We conclude that AQP1 does not regulate the endothelial EDH or NO
      dependent relaxation ex vivo or in vivo, but its deletion decreases baseline BP
      together with increased prostanoids-dependent relaxation in resistance vessels.
      Strikingly, this was associated with microcardia, unrelated to perturbed
      angiogenesis. This may raise interest for new inhibitors of AQP1 and their use to
      treat hypertrophic cardiac remodeling. 

PMID- 23873355
TI  - Vitamin D receptor gene silencing effects on differentiation of myogenic cell
      lines.
AB  - INTRODUCTION: The active form of vitamin D (1,25-dihydroxy-vitamin D3) is known
      to increase fast-type myosin heavy chain expression in differentiated myogenic
      cell lines. The mechanisms for this effect are not fully understood. The aim of
      this study was to determine the role of signals transmitted through the vitamin D
      receptor (VDR) during differentiation of myoblasts. METHODS: Electroporation was
      used to introduce VDR siRNA molecules into C2C12 and G8 murine myoblast cell
      lines. Gene and protein expression profiles of VDR-gene silenced cells were
      analyzed in vitro. RESULTS: Suppressing VDR expression by RNA interference
      resulted in inhibition of myogenic differentiation of C2C12 and G8 cell lines at
      both mRNA and protein levels. CONCLUSIONS: Our results suggest that myoblasts
      require signals transmitted through VDR for differentiation into myocytes and
      emphasize the importance of VDR expression in skeletal muscles for maintaining
      muscle volume in the elderly.

PMID- 23873356
TI  - Incremental value of transition zone and midline apical biopsy at baseline TRUS
      guided biopsy for prostate cancer detection.
AB  - PURPOSE: To determine the diagnostic yield of transition zone (TZB) and midline
      apical biopsies (MAB) in baseline transrectal ultrasound (TRUS)-guided biopsies
      and to establish whether TZB and MAB for the diagnosis of prostate cancer (PCa)
      add clinical relevant information. METHODS: We performed baseline 9-core TRUS
      guided biopsy in 412 consecutive subjects using sextant biopsies of the PZ (PZB),
      with an additional TZB on either side and a MAB at the prostatic apex. We
      determined the incremental diagnostic value of additional TZB an MAB to sextant
      PZB. RESULTS: Within a cohort of 412 patients with a median PSA of 7.5 ng/ml, 178
      (43.2 %) patients were diagnosed with PCa upon baseline TRUS-guided biopsies. In
      102 cases, at least one TZB was positive for PCa, with 6/412 (1.4 %) cases
      displaying PCa in the TZB only. MAB alone was positive for PCa in 4/412 (1.0 %)
      cases. One case (1/412; 0.2 %) had only a TZB and a MAB positive for PCa without
      positive PZB. Thus, 11/412 (2.7 %) of cases would not have been diagnosed with
      PCa at baseline TRUS-guided biopsy had only sextant PZ biopsy been performed. TZB
      detected a high-grade Gleason component (Gleason 4 and/or 5) not present in the
      PZB in 2.4 % of PCa cases. CONCLUSIONS: There is limited value for TZB and MAB in
      the context of sextant PZB at baseline TRUS-guided biopsies for PCa.

PMID- 23873358
TI  - Ionic liquids of superior thermal stability.
AB  - In a head-to-head study, ILs based upon tetraarylphosphonium cations exhibit
      superior long-term thermal stability compared to familiar salts based upon
      imidazolium, quaternary ammonium, or tetraalkylphosphonium cations. 

PMID- 23873357
TI  - Charlson score as a single pertinent criterion to select candidates for active
      surveillance among patients with small renal masses.
AB  - PURPOSE: The aim of the study was to assess the outcome after nephron-sparing
      surgery (NSS) of patients with small renal masses (SRMs) who would have been
      eligible for active surveillance (AS). METHODS: Data were collected
      retrospectively for 758 patients who underwent NSS over a 5-year period. Outcomes
      were assessed in two groups of patients who were eligible for AS according to
      different criteria. Group 1 criteria were as follows: age >75 years, renal mass
      <=4 cm, significant comorbidities [Charlson Comorbidity Index (CCI) >2]. Group 2
      criteria were as follows: any SRM <= 4 cm regardless of age, severe comorbidities
      with a 10-year mortality risk >50 % (CCI > 4). The two groups were not compared
      statistically because some patients were included in both. RESULTS: Fifty-five
      patients (7.3 %) were included in Group 1 and 62 (8.2 %) in Group 2. There was a
      significant proportion of benign tumours in Group 1 (N = 6; 11 %) and Group 2 (N
      = 6; 10 %). Six (11 %) positive margins were observed in Group 1 and 8 (13 %) in
      Group 2. The 2- and 5-year recurrence-free survival rates were 100 and 77.4 %,
      respectively, in Group 1, and 88.5 and 79.6 % in Group 2. The 2- and 5-year
      overall survival rates were 100 and 74.7 % in Group 1, and 96.7 and 78.1 % in
      Group 2. CONCLUSIONS: The majority of patients with SRMs who would have been
      eligible for AS had no recurrence after initial tumour removal. In these
      patients, a CCI > 4 appeared to be a pertinent criterion to identify those
      patients less likely to benefit from immediate surgery.

PMID- 23873359
TI  - Occupation and suicide: Colorado, 2004-2006.
AB  - BACKGROUND: Occupation has been identified as a risk factor for suicide. Changes
      in work environments over time suggest occupations at high risk of suicide may
      also change. Therefore, periodic examination of suicide by occupation is
      warranted. The purpose of this article is to describe suicide rates by
      occupation, sex, and means used in Colorado for the period 2004-2006. METHODS: To
      provide information useful in designing suicide prevention programs, the methods
      used in suicide across occupational groups also are examined. Data from the
      Colorado Violent Death Reporting System (COVDRS) were obtained for suicides that
      occurred between 2004 and 2006. Denominators to calculate rates by age, sex, and
      race used are from the 2000 US Census of the Population data. RESULTS: Men had
      higher suicide rates than women in all occupation categories except computers and
      mathematics. Among men, those in farming, fishing, and forestry (475.6 per
      100,000) had the highest age-adjusted suicide rates. Among women, workers with
      the highest suicide rates were in construction and extraction (134.3 per
      100,000). The examination of lethal means showed that workers in farming,
      fishing, and forestry had higher rates of suicide by firearms (50.18 per 100,000)
      compared with other workers. Healthcare practitioners and technicians had the
      highest rate of suicide by poisoning (14.25 per 100,000). Workers involved in
      construction and extraction (26.43 per 100,000) had higher rates of suicide by
      hanging, suffocation, or strangling. CONCLUSIONS: Significant differences in
      means of suicide were seen by occupation, which could guide future suicide
      prevention interventions that may decrease work-related suicide risks.

PMID- 23873361
TI  - DFT study on crystalline 1,1-diamino-2,2-dintroethylene under high pressures.
AB  - DFT calculations have been performed to study the structural, electronic,
      absorption, and thermodynamic properties of crystalline 1,1-diamino-2,2
      dintroethylene (alpha-FOX-7) in the pressure range of 0-40 GPa. A comprehensive
      analysis of the variation trends of the lattice constants, bond lengths, bond
      angles, and twist angles under compression shows that six structural
      transformations occur in alpha-FOX-7 at 2, 5, 11, 19, 29, and 35 GPa,
      respectively. The C1-N1 and C1-N2 bond lengths decrease much faster than any
      other bonds under compression, indicating that the C-NO2 cleavage is possible to
      trigger the decomposition of alpha-FOX-7. The intra-molecular H-bonding
      interaction weakens at 2 and 5 GPa, which may be caused by the structural
      transformations, but it then strengthens with the increasing pressure up to 40
      GPa. The inter-molecular H-bonding interaction strengthens with the increasing
      pressure. The band gap of alpha-FOX-7 increases at 11 GPa suddenly and decreases
      obviously at 19, 29, and 35 GPa, which are caused by the structural
      transformations. alpha-FOX-7 has relatively high optical activity at high
      pressure. All the structural transformations are endothermic and not spontaneous
      at room temperature.

PMID- 23873360
TI  - Association between oxidative stress and telomere length in Type 1 and Type 2
      diabetic patients.
AB  - BACKGROUND: Increasing evidence showed that telomere length was shorter in age
      related diseases, but the mechanism of this phenomenon is still unclear. AIM: To
      determine whether telomere shortening occurs in Type 1 diabetes (T1D) and Type 2
      diabetes (T2D), and explore the effect of antioxidant status on the telomere
      length. SUBJECTS AND METHODS: T2D patients (no.=62), T1D patients (no.=34), and
      non-diabetic subjects used as control (CTL) (no.=40) were included in this study.
      Leukocyte telomere length ratio (T/S ratio) was measured using a quantitative PCR
      and analyzed. Antioxidant status was estimated by human 8-hydroxy-desoxyguanosine
      quantization. Other biomarkers, such as fasting plasma glucose, fasting insulin,
      glycated hemoglobin (HbA1c) and lipid profile were also measured. RESULTS:
      Compared with CTL group [T/S ratio (mean +/- SD), 2.39 +/- 0.55], leukocyte
      telomere length was significantly shorter in T2D group (1.67 +/- 0.50) and T1D
      group (1.77 +/- 0.50). 8-OHdG that indicated oxidative stress was significantly
      higher in T2D (2.99 +/- 0.85 ng/ml) and T1D (2.03 +/- 0.92 ng/ml) group than in
      CTL group (0.90 +/- 0.46 ng/ml). T/S ratio was significantly negatively
      correlated with age, waist circumference, waist-to-hip ratio, diastolic blood
      pressure, fasting plasma glucose, HbA1c, homeostasis model assessment of insulin
      resistance and 8- OHdG in the whole population. 8-OHdG was independent risk
      factor for telomere shortening in both T1D (p=0.018) and T2D group (p=0.022).
      CONCLUSIONS: In our study, shorter telomere length and increased oxidative stress
      were observed in both T1D and T2D. Older people with central obesity,
      hyperglycemia, insulin resistance and severe antioxidant status tended to have
      shorter telomere length. In addition, 8- OHdG was an independent predictor for
      telomere length for both T1D and T2D patients.

PMID- 23873362
TI  - Evaluation of the single-dose pharmacokinetics of bilastine in subjects with
      various degrees of renal insufficiency.
AB  - BACKGROUND: Bilastine is a novel second-generation H1 antihistamine, which has
      not shown sedative or cardiotoxic effects in clinical trials and in post
      marketing experience so far, developed for the symptomatic treatment of allergic
      rhinoconjunctivitis and urticaria. It has recently been granted marketing
      authorization for these therapeutic indications in adults and adolescents at a
      once-daily oral dose of 20 mg in several European countries. OBJECTIVE: This
      study was conducted to determine the pharmacokinetics of bilastine at a single
      oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment
      in patients with renal insufficiency was assessed by comparing the exposure to
      bilastine in these subjects with the estimated exposure of a dose corresponding
      to the safety margin. METHODS: The study was an open-label, single-dose, parallel
      group study of the pharmacokinetics and safety of a single dose of bilastine. The
      study was conducted as an in-patient setting at a clinical pharmacology facility.
      A total of 24 male or female subjects aged 18-80 years were to be enrolled in
      four groups of six subjects each. The groups were as follows: (1) healthy
      [glomerular filtration rate (GFR) >80 mL/min/1.73 m(2)]; (2) mild renal
      insufficiency (GFR 50-80 mL/min/1.73 m(2)); (3) moderate renal insufficiency (GFR
      30-50 mL/min/1.73 m(2)); and (4) severe renal insufficiency (GFR <=30 mL/min/1.73
      m(2)). A single 20 mg bilastine tablet was administered in a fasted state. Blood
      and urine samples were collected from pre-dose up to 72 h post-dose for bilastine
      pharmacokinetic analysis. Pharmacokinetic results were summarized using
      appropriate descriptive statistics. RESULTS: There was a clear trend of
      increasing area under the plasma concentration-time curve (AUC) and maximum
      plasma concentration (C(max)) through the groups 1-4. The mean AUC from time zero
      to infinity (AUC(infinity)) ranged from 737.4 to 1708.5 ng.h/mL in healthy
      subjects and severely impaired subjects, respectively. No significant differences
      among groups in median time to reach Cmax (tmax) or in the mean terminal
      disposition rate constants for bilastine were found. Renal and plasma clearance
      paralleled GFR. In all groups of renally impaired subjects the corresponding 90 %
      confidence interval of both AUC(infinity) and AUC from time zero to time of last
      measurable plasma concentration (AUC(last)) were not within the 0.8-1.25
      interval, indicating that bioequivalence between groups could not be
      demonstrated. The majority of bilastine was excreted within the first 12 h, and
      elimination was essentially complete by 72 h. CONCLUSION: An oral dose of
      bilastine (20 mg) was well-tolerated in renal insufficiency, despite the increase
      in exposure. The oral plasma clearance to renal clearance ratio [(CL(P)/F)/CL(R)]
      was approximately equal in the different groups, suggesting that renal excretion
      was the main elimination route for bilastine, and no alternative elimination
      routes were used even in severe renal insufficiency. Although exposure to
      bilastine was higher in renally impaired subjects, it remained well within the
      safety margins, thus allowing the conclusion that a 20-mg daily dose can be
      safely administered to subjects with different degrees of renal insufficiency
      without the need for dose adjustments.

PMID- 23873363
TI  - Infant health and neurodevelopmental outcomes following prenatal exposure to
      duloxetine.
AB  - Maternal psychiatric disorders can have negative consequences on the fetus and
      newborn. Thus, the risks of untreated mental disorders in pregnancy should be
      balanced against the potential risks of a psychopharmacological treatment. The
      aim of the present report is to provide information on the infant safety of
      duloxetine exposure, an antidepressant drug belonging to the serotonin
      norepinephrine reuptake inhibitors, during pregnancy. Despite duloxetine being
      routinely prescribed as a treatment for major depression and anxiety disorders,
      there is a paucity of literature evaluating both the short- and long-term effects
      of duloxetine exposure in utero. This paper provides data on infant health and
      neurodevelopmental outcomes, up to 9 months of age, in a newborn exposed to
      duloxetine throughout pregnancy. Although the present report suggests that
      duloxetine was not associated with major malformations or neurobehavioural
      problems, the drug should be used with caution until further information is
      available on its safety profile in pregnancy.

PMID- 23873364
TI  - Symposium in honor of Ralph L. Brinster celebrating 50 years of scientific
      breakthroughs.
AB  - The Symposium speakers comprised a distinguished group of scientists from North
      America, Europe and Asia. The Keynote address was presented by Michael Brown,
      Nobel Laureate in Physiology or Medicine (1985), and a plenary lecture was
      presented by John Gurdon, who within the next months would receive the Nobel
      Prize in Physiology or Medicine (2012). The first lecture in the series was
      presented by Richard Palmiter, Ralph?s collaborator for more than 15 years, and
      he provided an overview of their work together followed by Richard?s subsequent
      exciting contributions in the area of neurobiology. Seventeen lectures were
      presented over the two-day Symposium by distinguished scientists, including
      several of Ralph's former colleagues and students. The topics covered studies on
      germ cells, the germline, early embryos and their differentiation, as well as
      exciting and unpublished studies on stem cells and reprogramming. Many of the
      topics presented arose from foundation experiments in which Ralph participated,
      and these new developments indicate the dramatic progression of studies in this
      area. The Symposium program and the complete lectures can be found at the
      following link: www.vet.upenn.edu/BrinsterSymposium. 

PMID- 23873365
TI  - Lateral inhibition and neurogenesis: novel aspects in motion.
AB  - Neuronal production in metazoans is tightly controlled by Delta/Notch-dependent
      signals regulating lateral inhibition. It is currently thought that lateral
      inhibition takes place in clusters of precursors with equal capacity to trigger
      and receive Notch-dependent inhibitory signals. However, this view neglects
      crucial dynamical aspects of the process. In this review, we discuss two of these
      dynamic factors, whose alterations yield dysfunctions in neurogenesis. First,
      precursors show variable neurogenic capacity as they go through the cell cycle.
      Second, differentiating precursors are in direct contact with non-neurogenic
      cells at the wavefront of expanding neurogenic domains. We discuss the mechanisms
      adopted by Metazoa to prevent these dysfunctions in the lateral inhibitory
      process, which include cell cycle synchronization occurring in the invertebrate
      neural epithelium and during primary neurogenesis in anamniotes, interkinetic
      nuclear movement in the vertebrate neuroepithelium and generalized Delta
      expression ahead of the neurogenic wavefront. The emerging concept is that
      lateral inhibition during neurogenesis occurs in dynamic clusters of precursors
      and requires specific mechanisms to avoid distortions resulting from the
      interaction between neurogenic and non-neurogenic precursors. The advance in
      visualizing Notch dynamics with real-time imaging at cellular and subcellular
      levels will notably contribute to our understanding of these novel "aspects of
      motion" in neurogenesis.

PMID- 23873366
TI  - Sexual dimorphism in estrogen-induced synaptogenesis in the adult hippocampus.
AB  - It has long been known that estradiol influences synaptic plasticity in the
      female hippocampus. The density of dendritic spines varies during the estrous
      cycle and correlates positively with varying levels of estradiol in serum. In
      accordance, ovariectomy results in a loss of spines that can be rescued by
      estradiol treatment in animals, suggesting that estradiol originating from the
      ovaries induces spine formation in the hippocampus. More recent studies point to
      a role of hippocampus-derived estradiol in synaptogenesis in the female
      hippocampus, rather than of estradiol of ovarian origin. In our studies, we have
      shown that inhibition of hippocampal estrogen synthesis results in spine synapse
      loss in female animals and, more importantly, also in ovariectomized animals.
      Surprisingly, inhibition of local estradiol synthesis had no effect on synapse
      formation in males, in spite of a similar capacity to synthesize estradiol in
      male and female hippocampal neurons. In females, neuro-sexual steroid production
      is promoted by hypothalamic, cyclic GnRH release and likely underlies the estrus
      cyclicity of spine synapse density in the hippocampus. As a result, peripheral
      serum concentrations of estradiol determine the amount of estradiol synthesis in
      the hippocampus. This paradigm may also be true in males. In support of this
      hypothesis, we found that the content of estradiol in hippocampal tissue is
      higher in female compared to that in male animals, with low levels of estradiol
      in serum and tonic and acyclical GnRH release. In summary, our data point to
      important sex-specific differences in sexual steroid-induced synaptogenesis. 

PMID- 23873367
TI  - SMYD2 is induced during cell differentiation and participates in early
      development.
AB  - Histone modifying enzymes play critical roles in cell differentiation and
      development. In this study, we report that SMYD2 (SET and MYND domain containing
      protein 2), a histone lysine methyltransferase, is induced during human embryonic
      stem (ES) cell differentiation and it is preferentially expressed in somatic
      cells versus pluripotent cells. Knockdown of SMYD2 in human ES cells promotes the
      induction of endodermal markers during differentiation, while overexpression has
      opposite effects. In vivo experiments in zebrafish revealed that knockdown of
      smyd2a (a homologue gene of human SMYD2) causes developmental delay and aberrant
      tail formation, which is coincident with low expression of ntl and over induction
      Nodal-related genes during gastrulation. Taken together, these findings suggest
      that SMYD2 plays a critical role at early stages of development and in human ES
      cell differentiation. 

PMID- 23873368
TI  - Trans-2-phenylcyclopropylamine regulates zebrafish lateral line neuromast
      development mediated by depression of LSD1 activity.
AB  - The zebrafish mechanosensory lateral line (LL) is a model system for the study of
      hair cell development, survival and regeneration. Recently, histone modifications
      have attracted a considerable amount of interest because of their indispensable
      roles in various kinds of cellular processes including differentiation,
      proliferation, apoptosis and function. Lysine specific demethylase 1 (LSD1) is an
      important enzyme that regulates histone methylation. As a transcriptional
      regulator, this enzyme has broad functional activities and is involved in many
      biological processes. However, the effects of LSD1 on the early development of
      zebrafish sensory system have not been fully elucidated. Here, we have found that
      pharmacological inhibition of LSD1 with the monoamine oxidase (MAO) inhibitor
      trans-2-phenylcyclopropylamine (referred to as 2-PCPA) reduced the numbers of
      both sensory hair cells and supporting cells of neuromasts during zebrafish
      development. Our results showed that the treatment of zebrafish larvae with 2
      PCPA caused accumulation of histone methylation and suppressed proliferation of
      neuromast cells. Finally, acridine orange staining assay demonstrated that 2-PCPA
      treatment at high concentrations induced an enhancement of cellular apoptosis
      within neuromasts. Taken together, these results indicate that LSD1 demethylase
      activity is required for neuromast development in zebrafish larvae. 

PMID- 23873369
TI  - The Dictyostelium prestalk inducer DIF-1 directs phosphorylation of a bZIP
      transcription factor.
AB  - DIF-1, a chlorinated hexaphenone produced by developing Dictyostelium cells,
      induces prestalk differentiation. DimB is a bZIP transcription factor that
      accumulates in the nucleus upon exposure to DIF-1, where it directly activates
      transcription of DIF-responsive genes. The signaling steps upstream of DimB and
      downstream of DIF-1 are entirely unknown. Analysis by mass spectrometry shows
      that incubation with DIF-1 rapidly stimulates phosphorylation at several sites in
      DimB. We characterize the most highly responsive site, S590, which is located
      very close to the C terminus. A point mutation in this site, S590A, does not
      inhibit DimB nuclear accumulation in response to DIF. However, this seems likely
      to reflect functional redundancy with other sites; because a panel of chemical
      variants on the structure of DIF-1 show a correlation between their potencies as
      inducers of DimB nuclear accumulation and their potencies as inducers of
      phosphorylation at S590. Furthermore, the S590A mutant is fully active in mutant
      rescue of a dimB null strain, arguing against an alternative role in
      transcriptional activation of target genes. We conclude that i) DIF-1 directs
      phosphorylation at S590, ii) although it is not essential for nuclear
      accumulation in response to DIF-1 correlative evidence, based upon a panel of DIF
      1 related molecules, suggests that this modification may play a redundant role in
      the process. iii) We also present evidence that the kinase activity, which
      phosphorylates S590, is non-nuclear and that this signalling pathway is, in part
      at least, independent of the DIF-regulated STATc activation pathway. 

PMID- 23873370
TI  - Induction of intermediate mesoderm by retinoic acid receptor signaling from
      differentiating mouse embryonic stem cells.
AB  - Renal lineages including kidney are derived from intermediate mesoderm, which are
      differentiated from a subset of caudal undifferentiated mesoderm. The inductive
      mechanisms of mammalian intermediate mesoderm and renal lineages are still poorly
      understood. Mouse embryonic stem cells (mESCs) can be a good in vitro model to
      reconstitute the developmental pathway of renal lineages and to analyze the
      mechanisms of the sequential differentiation. We examined the effects of Activin
      A and retinoic acid (RA) on the induction of intermediate mesoderm from mESCs
      under defined, serum-free, adherent, monolayer culture conditions. We measured
      the expression level of intermediate mesodermal marker genes and examined the
      developmental potential of the differentiated cells into kidney using an ex vivo
      transplantation assay. Adding Activin A followed by RA to mESC cultures induced
      the expression of marker genes and proteins for intermediate mesoderm, odd
      skipped related 1 (Osr1) and Wilm?s Tumor 1 (Wt1). These differentiated cells
      integrated into laminin-positive tubular cells and Pax2-positive renal cells in
      cultured embryonic kidney explants. We demonstrated that intermediate mesodermal
      marker expression was also induced by RA receptor (RAR) agonist, but not by
      retinoid X receptor (RXR) agonists. Furthermore, the expression of these markers
      was decreased by RAR antagonists. We directed the differentiation of mESCs into
      intermediate mesoderm using Activin A and RA and revealed the role of RAR
      signaling in this differentiation. These methods and findings will improve our
      understanding of renal lineage development and could contribute to the
      regenerative medicine of kidney. 

PMID- 23873371
TI  - The Parahox gene Pdx1 is required to maintain positional identity in the adult
      foregut.
AB  - The homeobox gene Pdx1 is a key regulator of pancreas and foregut development.
      Loss of Pdx1 expression results in pancreas agenesis and impaired development of
      the gastro-duodenal domain including Brunner?s glands. We previously demonstrated
      a key role for Pdx1 in maintaining the integrity and function of insulin
      secreting beta cells in the adult pancreas. In the present study, we aimed to
      determine if expression of Pdx1 is required to maintain the cellular identity of
      the gastro-duodenal domain in adult mice. Immunohistological studies were
      performed in a mouse model in which expression of Pdx1 was conditionally
      repressed with the doxycycline-responsive tetracycline transactivator system.
      Mice in which Pdx1 was chronically repressed developed hamartomas in the gastro
      duodenal domain. These lesions appeared to arise from ectopic foci of
      anteriorized cells, consistent with a localised anterior homeotic shift. They
      emerge with the intercalation of tissue between the anteriorized and normal
      domains and appear strikingly similar to lesions in the colon of mice
      heterozygous for another Parahox gene, Cdx2. Continuing expression of Pdx1 into
      adult life is required to maintain regional cellular identity in the adult
      foregut, specifically at the gastro-duodenal boundary. Loss of Pdx1 expression
      leads to anterior transformation and intercalary regeneration of ectopic tissue.
      We propose a model in which the posterior dominance of classical Hox genes is
      mirrored by the Parahox genes, providing further evidence of the functional
      conservation of the Parahox genes. These findings may have implications for
      further understanding the molecular basis of gastro-duodenal metaplasia and
      gastro-intestinal transformations such as Barrett?s esophagus. 

PMID- 23873372
TI  - Hippo signaling components, Mst1 and Mst2, act as a switch between self-renewal
      and differentiation in Xenopus hematopoietic and endothelial progenitors.
AB  - Hippo signaling is a conserved pathway that regulates cell proliferation and
      organ size control. Mst1 and Mst2 were identified as homologs of hippo and as
      core kinases of the Hippo pathway in mammals. Here, we have characterized the
      role of Mst1 and Mst2 during Xenopus primitive hematopoiesis. We showed that Mst1
      and Mst2 were strongly expressed in the Xenopus ventral blood island, where
      primitive hematopoiesis is initiated. Loss-of-function analysis of Mst1/2
      revealed morphogenetic defects, including short axis, smaller eyes and abnormal
      epidermis, and decreased phosphorylation of Yap. Mst1/2 morphants did not exhibit
      any change in the expression of hematopoietic and endothelial progenitor markers
      in early hematopoietic development. In addition, we have shown that such
      progenitor markers were continuously expressed through to the late hematopoietic
      development stage. As a result, the expression of erythroid, myeloid and
      endothelial differentiation markers were decreased in Mst1/2 morphants. Our
      results indicate that Mst1/2 act as a differentiation switch in Xenopus
      hematopoietc and endothelial progenitors. 

PMID- 23873373
TI  - Unc-5/netrin-mediated axonal projection during larval serotonergic nervous system
      formation in the sea urchin, Hemicentrotus pulcherrimus.
AB  - The molecular structure and role of two splice-isoforms of Unc-5 (Hp-Unc-5v1 and
      v2) in Unc-5/netrin interaction during serotonergic axonal projection were
      elucidated in this study. Hp-Unc-5v1 was found to be comprised of two
      immunoglobulin-like domains, two thrombospondin domains in the extracellular
      region, and ZU-5, DB, and Death domains in the cytoplasmic region, whereas Hp-Unc
      5v2 lacked one thrombospondin domain, the transmembrane domain, and all
      cytoplasmic domains. Hp-Unc-5v1 was transcribed in unfertilized eggs, which
      continued until the 3-day post-fertilization (-dpf) 2-arm pluteus stage, but was
      suspended at the mesenchyme blastula stage (mB1), whereas Hp-Unc-5v2 was not
      transcribed in unfertilized eggs, but was from after fertilization to the same
      developmental stage of mB1 as Hp-Unc-5v1. Relative accumulation of transcripts of
      both splice-isoforms peaked at the prism stage and declined thereafter, and they
      were localized at the vegetal pole region of early gastrulae, around the
      blastopore in mid- to late gastrulae, at fore- and mid-gut regions and on the
      basal side of dorsal ectoderm in 28-hour post-fertilization prism larvae, and
      within axons at and after the 2-dpf pluteus stage. Hp-Unc-5v2:GFP was detected in
      the entire serotonergic cell body and extracellularly on the basal surface of
      oral ectoderm in 2-dpf plutei and exclusively within axons in 4-dpf plutei.
      Overexpression of Hp-Unc-5v2 resulted in decreased axonal projection in plutei.
      Knockdown of Hp-Unc-5v1 by morpholino antisense oligonucleotide resulted in
      severe deficiency of axonal projection. Interference of Unc-5/netrin interaction
      using an exogenous synthetic SQDFGKTW peptide from the VI domain in Hp-netrin
      inhibited axonal projection and larval swimming. 

PMID- 23873374
TI  - Calnexin is required for zebrafish posterior lateral line development.
AB  - The lateral line is a mechanosensory system in fish and amphibians to detect
      local water flow and pressure. Development of the posterior lateral line (PLL)
      originates from the migrating PLL primordium (PLLP). The PLLP deposits neuromasts
      on the trunk during migration to the tail. Molecular dissection revealed that PLL
      development is associated with genes mediating cell adhesion, morphogenesis,
      neurogenesis and development, but the regulatory signaling network is far from
      completion. To further investigate candidate regulatory genes for lateral line
      development, we found using whole-mount in situ hybridization that calnexin, an
      endoplasmic reticular (ER) calcium-binding protein gene, is expressed in PLL
      neuromasts. Knockdown of calnexin using antisense morpholino oligonucleotides
      resulted in a dose-dependent reduction in neuromasts and hair cells of the PLL.
      Using a transgenic claudin b:gfp line, we observed a notably reduced PLLP size,
      but no significant migration defect in calnexin morphants. Finally, we discovered
      that the reduced PLLP is associated with a reduction in cell proliferation and an
      increase in ER stress-dependent apoptosis. These results suggest that calnexin is
      essential for neuromast formation during lateral line development in the
      zebrafish. 

PMID- 23873375
TI  - Germes is involved in translocation of germ plasm during development of Xenopus
      primordial germ cells.
AB  - Germes mRNA and protein are components of the germ plasm in Xenopus laevis.
      Previously, based on phenotypic observations of tailbud embryos expressing intact
      and mutant Germes, it was suggested that Germes is involved in the organization
      of germ plasm (Berekelya et al., 2007). Recently, to observe the germ plasm in a
      living embryo, we generated transgenic Xenopus expressing EGFP fused with a
      mitochondrial targeting signal, because germ plasm is enriched with mitochondria
      (Taguchi et al., 2012). Using this transgenic Xenopus, we demonstrate that Germes
      plays an essential role in the translocation of germ plasm from the cortex to the
      perinuclear region in primordial germ cells during early gastrulation. 

PMID- 23873376
TI  - Probing the surface of nanosheet H-ZSM-5 with FTIR spectroscopy.
AB  - Herein we report FTIR in situ adsorption of molecular hydrogen, carbon monoxide,
      water, methanol, pyridine and 2,4,6-trimethylpyridine (collidine) on nanosheet H
      ZSM-5 which was recently studied in the methanol to hydrocarbons (MTH) reaction.
      The nature of the hydroxyl groups and surface species are described in detail.
      The IR spectrum of nanosheet H-ZSM-5 is dominated by silanols, which saturate the
      external surfaces. The acidity of Si(OH)Al is comparable to that observed in the
      case of standard microcrystalline H-ZSM-5. The study of the external surface
      allows the recognition of Si(OH)Al species located at the channel entrance, which
      are mostly all accessible to hindered molecules such as collidine. 

PMID- 23873377
TI  - Protein purification by aminosquarylium cyanine dye-affinity chromatography.
AB  - The most selective purification method for proteins and other biomolecules is
      affinity chromatography. This method is based on the unique biological-based
      specificity of the biomolecule-ligand interaction and commonly uses biological
      ligands. However, these ligands may present some drawbacks, mainly because of
      their cost and lability. Dye-affinity chromatography overcomes the limitations of
      biological ligands and is widely used owing to the low cost of synthetic dyes and
      to their resistance to biological and chemical degradation. In this work,
      immobilized aminosquarylium cyanine dyes are used in order to exploit affinity
      interactions with standard proteins such as lysozyme, alpha-chymotrypsin and
      trypsin. These studies evaluate the affinity interactions occurring between the
      immobilized ligand and the different proteins, as a reflection of the sum of
      several molecular interactions, namely ionic, hydrophobic and van der Waals,
      spread throughout the structure, in a defined spatial manner. The results show
      the possibility of using an aminosquarylium cyanine dye bearing a N-hexyl pendant
      chain, with a ligand density of 1.8 * 10(-2) mmol of dye/g of chromatographic
      support, to isolate lysozyme, alpha-chymotrypsin and trypsin from a mixture. The
      application of a decreasing ammonium sulfate gradient resulted in the recovery of
      lysozyme in the flowthrough. On the other hand, alpha-chymotrypsin and trypsin
      were retained, involving different interactions with the ligand. In conclusion,
      this study demonstrates the potential applicability of ligands such as
      aminosquarylium cyanine dyes for the separation and purification of proteins by
      affinity chromatography.

PMID- 23873378
TI  - Homocysteine levels in patients with schizophrenia on clozapine monotherapy.
AB  - We tested the hypothesis that homocysteine levels are higher in blood of
      schizophrenic subjects on clozapine monotherapy than in healthy controls and they
      correlate with anthropometric measurements, laboratory tests and results of
      bioimpedance analysis of body composition. Data for 24 subjects with
      schizophrenia treated with clozapine and 24 age- and sex-matched healthy
      volunteers was analyzed. Regarding the whole group, homocysteine levels were
      significantly higher in men (17.0 +/- 3.4 vs. 12.1 +/- 4.0 MUmol/L, p = 0.009).
      Homocysteine levels correlated with waist circumference (R = 0.58, p = 0.003),
      waist-to-hip ratio (R = 0.57, p = 0.003), basal metabolic rate (R = 0.48, p =
      0.01), lean body mass [kg] (R = 0.53, p = 0.008), body water [L] (R = 0.53, p =
      0.008) and triglycerides (R = 0.57, p = 0.003). There were no significant
      differences of homocysteine levels for impaired fasting glucose, abdominal
      obesity, obesity/overweight, and dyslipidemia. Homocysteine levels did not
      correlate with age, treatment duration, clozapine dose, weight, body mass index,
      abdominal circumference, blood pressure, total body fat, cholesterol, high
      density lipoproteins, low density lipoproteins, uric acid, calcium, glucose,
      insulin, homoeostasis model assessment of insulin resistance 1, and homoeostasis
      model assessment of insulin resistance 2. We did not find significant differences
      in blood homocysteine levels between subjects with schizophrenia and controls.
      Association with waist circumference may support homocysteine role as an
      important cardiovascular risk factor. Association with lean weight may explain
      why men have higher levels of homocysteine than women.

PMID- 23873379
TI  - Selectively catalytic hydrodefluorination of perfluoroarenes by Co(PMe3)4 with
      sodium formate as reducing agent and mechanism study.
AB  - Successful selective hydrodefluorinations of aryl fluorides were carried out in
      the presence of a cobalt catalyst supported by trimethylphosphine and with sodium
      formate as a reducing agent in acetonitrile or DMSO. Octafluorotoluene (1),
      pentafluoropyridine (2), hexafluorobenzene (3), pentafluorobenzene (3a) and
      perfluorobiphenyl (4) were studied to investigate the scope of this catalytic
      system. It was found that the fluorinated compounds 1, 2 and 4 with electron
      withdrawing groups are more active than 3 and 3a. The catalytic
      hydrodefluorination mechanism is proposed and discussed with the support of the
      experimental results of the stoichiometric reactions and the in situ IR and NMR
      data. 

PMID- 23873380
TI  - First experience with the deltastream(R) DP3 in venovenous extracorporeal
      membrane oxygenation and air-supported inter-hospital transport.
AB  - OBJECTIVES: Based on continuous technical innovations and recent research,
      extracorporeal membrane oxygenation (ECMO) has become a promising tool in the
      treatment of patients with acute (cardio)pulmonary failure. Nevertheless, any
      extracorporeal technique requires a high degree of experience and knowledge, so
      that a restriction to specialized centres seems to be reasonable. As a
      consequence of this demand, the need for inter-hospital transfer of patients with
      severely impaired (cardio)pulmonary function is rising. Unfortunately, most of
      the ECMO devices used in the clinical setting are not suitable for inter-hospital
      transport because of their size, weight or complexity. In this article, we
      describe our first experiences with the airborne transport of 6 patients on a new
      portable, miniaturized and lightweight extracorporeal circulation system, the
      Medos deltastream(r) DP3. METHODS: Six patients suffering acute respiratory
      failure were taken on venovenous ECMO (DP3) out-of-centre and transferred to the
      University Medical Center Regensburg by helicopter. All cardiorespiratory
      relevant parameters of the patients and the technical functioning of the device
      were continuously monitored and documented. RESULTS: Implantation of the device
      and air-supported transport were performed without any technical complications.
      The patients were transported from a distance of 66-178 km, requiring a time of
      40-120 min. With the help of the new deltastream(r) DP3 ECMO device, a prompt
      stabilization of the cardiopulmonary function could be achieved in all patients.
      One patient was under ongoing cardiopulmonary resuscitation by the time our ECMO
      team arrived at the peripheral hospital and died shortly after arrival in the
      central emergency ward. CONCLUSIONS: Our experience shows that the deltastream(r)
      DP3 is an absolutely reliable and safe ECMO device that could gain growing
      importance in the field of airborne transportation of patients on ECMO due to its
      unsophisticated, miniaturized and lightweight characteristics.

PMID- 23873381
TI  - Hydrolysis of the quinone methide of butylated hydroxytoluene in aqueous
      solutions.
AB  - Butylated hydroxytoluene or BHT is an antioxidant commonly used in pharmaceutical
      formulations. BHT upon oxidation forms a quinone methide (QM). QM is a highly
      reactive electrophilic species that can undergo nucleophilic addition. Here, the
      kinetic reactivity of QM with water at various apparent pH values in a 50% (v/v)
      water-acetonitrile solution at constant ionic strength of I = 0.5 (NaCl)4 , was
      studied. The hydrolysis of QM in the presence of added acid, base, sodium
      chloride, and phosphate buffer resulted in the formation of only one product--the
      corresponding 3,5-di-tert-butyl-4-hydroxybenzyl alcohol (BA). The rate of BA
      formation was catalyzed by the addition of acid and base, but not chloride and
      phosphate species. Nucleophilic excipients, used in the pharmaceutical
      formulation, or nucleophilic groups on active pharmaceutical ingredient molecule
      may form adducts with QM, the immediate oxidative product of BHT degradation,
      thus having implications for drug product impurity profiles. Because of these
      considerations, BHT should be used with caution in formulations containing drugs
      or excipients capable of acting as nucleophiles.

PMID- 23873382
TI  - Mesenchymal stem cells utilize CXCR4-SDF-1 signaling for acute, but not chronic,
      trafficking to gastric mucosal inflammation.
AB  - BACKGROUND: Helicobacter infection is the main risk factor in developing gastric
      cancer. Mesenchymal stem cells (MSCs) are non-hematopoietic stromal cells, which
      are able to differentiate into different cell lineages. MSC contribute to cancer
      development by forming the tumor directly, contributing to the microenvironment,
      or by promoting angiogenesis and metastasis. CXCR4/SDF-1 axis is used by MSC in
      trafficking, homing, and engraftment at chronic inflammation sites, and plays an
      important role in tumorigenesis. AIM: To determine if CXCR4 receptor has a role
      in MSC contribution to the development of Helicobacter-mediated gastric cancer.
      METHODS: SDF-1 and CXCR4 expression in mouse gastric mucosa in the setting of
      acute and chronic inflammation was measured using RT-PCR. Mouse culture-adapted
      MSC express CXCR4. Wild-type C57BL/6 mice infected with Helicobacter felis for 6
      months or controls were given IV injections of CXCR4 knock-down MSC. Animals were
      followed for another 4 months. Homing of MSC in the stomach was quantified using
      RT-PCR. MSC differentiation into gastric epithelia lineages was analyzed using
      immunohistochemistry and fluorescent in situ hybridization. RESULTS: CXCR4 and
      SDF-1 are both upregulated in the settings of Helicobacter-induced chronic
      gastric inflammation. CXCR4 is fully required for homing of MSC to the stomach in
      acute gastric inflammation, but only partially in Helicobacter-induced gastric
      cancer. MSC lead to gastric intraepithelial neoplasia as early as 10 months of
      Helicobacter infection. CONCLUSIONS: Our results show that MSC have a tumorigenic
      effect by promoting an accelerated form of gastric cancer in mice. The
      engraftment of MSC in chronic inflammation is only partially CXCR4-dependent.

PMID- 23873383
TI  - Epigenetics in gastrointestinal stromal tumors: clinical implications and
      potential therapeutic perspectives.
AB  - Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal
      neoplasms affecting the gastrointestinal tract. Activating mutations in either
      the KIT or PDGFRa gene are the principal oncogenic triggers with the former
      accounting for more than 80 % of cases. In the small subset of GIST that are wild
      type for both the aforementioned changes, other germline or somatic mutations
      have been identified. GIST exhibit a highly variable clinical behavior and the
      main prognostic determinants are tumor size, mitotic rate, and location. It is,
      however, strongly believed that, beyond classic genetics, additional epigenetic
      phenomena such as DNA hypomethylation and hypermethylation, microRNA alterations,
      and chromatin modifications underlie GIST tumorigenesis and influence the
      clinical course and response to standard treatment. This review aims to
      illuminate current advances in terms of epigenetics in GIST, as well as possible
      implications in prognosis and therapeutics.

PMID- 23873385
TI  - Preparation and characterization of poly(ethyl hydrazide)-grafted oil palm empty
      fruit bunch fibre for the removal of Cu(II) ions from an aqueous environment.
AB  - Poly(ethyl hydrazide)-grafted oil palm empty fruit bunch fibre (peh-g-opefb) was
      successfully prepared by heating poly(methyl acrylate)-grafted opefb (pma-g
      opefb) at 60  degrees C for 4 h with a solution of hydrazine hydrate (15% v/v) in
      ethanol. The Fourier transform infrared spectrum of the product shows a secondary
      amine peak at 3267 cm-1, with amide carbonyl peaks at 1729 cm-1 and 1643 cm-1.
      The chelating ability of peh-g-opefb was tested with copper ion in aqueous
      solution. A batch adsorption study revealed that maximum adsorption of copper ion
      was achieved at pH 5. An isotherm study showed the adsorption follows a Langmuir
      model, with a maximum adsorption capacity of 43.48 mg g-1 at 25  degrees C. A
      kinetic study showed that the adsorption of copper ion rapidly reaches
      equilibrium and follows a pseudo-second-order kinetic model, with a constant rate
      of 7.02 * 10-4 g mg-1 min-1 at 25  degrees C. The Gibbs free energy, ?G0, value
      is negative, indicating a spontaneous sorption process. Entropy, ?S0, gives a
      positive value, indicating that the system is becoming increasingly disordered
      after the adsorption of copper ion. A positive enthalpy value, ?H0, shows that
      the endothermic process takes place during the adsorption and is more favourable
      at high temperatures.

PMID- 23873386
TI  - Hydrophosphonylation of nanoparticle Schiff bases as a mean for preparation of
      aminophosphonate-functionalized nanoparticles.
AB  - The development of nanotechnology is responsible for an increase in the
      achievements in medical diagnostics and in the preparation of new therapeutic
      vehicles. In particular, magnetic nanoparticles with a modified surface are a
      very attractive alternative to deliver therapeutic agents. We describe the
      modification of the surface of the iron oxide nanoparticles with aminophosphonic
      acids by applying the classic hydrophosphonylation approach. 

PMID- 23873387
TI  - Preliminary phytochemical screening and antibacterial properties of crude stem
      bark extracts and fractions of Parkia biglobosa (Jacq.).
AB  - A methanolic crude extract of Parkia biglobosa was prepared and later partitioned
      in succession with different solvents of increasing polarity ranging from n
      hexane, chloroform and ethyl acetate to butanol. Phytochemical screening of the
      extract revealed the presence of alkaloids, tannins, saponins, flavonoids,
      steroids, glycoside and sugars. The inhibition zones exhibited by the extract
      against the tested bacteria ranged between 14 +/- 0.00 mm (against Escherichia
      coli) and 28 +/- 0.71 mm (against Pseudomonas aeruginosa). The MIC of the
      methanolic extract of P. biglobosa against isolates ranged between 0.63 mg/mL and
      5 mg/mL, while the MIC values exhibited by the n-hexane and aqueous fractions
      ranged between 0.63 mg/mL and 10 mg/mL. Overall the extract and fractions of P.
      biglobosa used in this work were found to possess antimicrobial properties which
      compared favourably with those of streptomycin. These observations make this
      plant a potential source of bioactive compounds that can be used in management of
      bacterial infections. The use of this plant as herbal medicaments in African
      countries and the reports on the toxicity of the plant further show that the
      plant is non-toxic to humans. 

PMID- 23873388
TI  - Decomposition mechanisms and kinetics of novel energetic molecules BNFF-1 and
      ANFF-1: quantum-chemical modeling.
AB  - Decomposition mechanisms, activation barriers, Arrhenius parameters, and reaction
      kinetics of the novel explosive compounds, 3,4-bis(4-nitro-1,2,5-oxadiazol-3-yl)
      1,2,5-oxadiazole (BNFF-1), and 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(4-nitro-1,2,5
      oxadiazol-3-yl)-1,2,5-oxadiazole (ANFF-1) were explored by means of density
      functional theory with a range of functionals combined with variational
      transition state theory. BNFF-1 and ANFF-1 were recently suggested to be good
      candidates for insensitive high energy density materials. Our modeling reveals
      that the decomposition initiation in both BNFF-1 and ANFF-1 molecules is
      triggered by ring cleavage reactions while the further process is defined by a
      competition between two major pathways, the fast C-NO2 homolysis and slow nitro
      nitrite isomerization releasing NO. We discuss insights on design of new
      energetic materials with targeted properties gained from our modeling.

PMID- 23873389
TI  - Two new chiratane-type triterpenoids from Swertia kouitchensis.
AB  - Two rare new chiratane-type triterpenoids, kouitchenoids A and B (1, 2), together
      with oleanolic acid (3) and ursolic acid (4), were isolated from ethanol extract
      of Swertia kouitchensis. The new structures were determined by the analysis of MS
      and NMR data. In addition, compounds 1-4 showed moderate inhibitory activity
      against the alpha-glucosidase (with IC50 values ranging from 1,812 to 2,027 MUM).

PMID- 23873390
TI  - A straightforward diphenylmethyl protection method and deprotection of some
      pyrimidine nucleosides.
AB  - Benzhydryl protection of primary and secondary alcohols has been reported
      previously via reaction with metal alcoholates. Our aim was to find generally
      useful and very mild conditions for the alcoholic protection and deprotection of
      nucleosides with the diphenylmethyl group. This was accomplished for some
      pyrimidine nucleosides using PdCl2 as the transition metal catalyst, and with
      optimization yields of 70-90% have been achieved. A lack of solubility of other
      nucleosides hampers its more general use.

PMID- 23873391
TI  - Surveillance and characterisation of Cronobacter spp. in Czech retail food and
      environmental samples.
AB  - Cronobacter spp. (formerly Enterobacter sakazakii) are emerging, opportunistic
      pathogens that are linked with food-borne infections in neonates and infants. In
      the present study, 291 samples of food, 36 samples from a dairy farm and 140
      samples of dust from vacuum cleaners were examined for the presence of
      Cronobacter spp. using chromogenic media and biochemical tests. Altogether, 72
      Cronobacter spp. strains were isolated in accordance with the reference standard
      CSN P ISO/TS 22964 (2006). No Cronobacter spp. strains were detected in 10
      samples of infant milk formula or in samples from a dairy farm. Twelve out of 20
      positive food samples were dry products. The incidence of Cronobacter spp. in
      instant and powdered products and spices (12 positive isolates out of 82 samples)
      was significantly higher than that in other foods (P = 0.002), but lower than
      that in samples of dust (52 isolates; P < 0.001). The incidence of Cronobacter
      spp. in dust from restaurants, bars and hotels (13 positive isolates in 20
      samples) was significantly higher than that in dust from households (P = 0.010).
      The polymerase chain reaction assay for the species-specific detection of the
      rpoB gene was performed in 49 isolates. Thirty-four Cronobacter spp. isolates
      were identified as Cronobacter sakazakii, nine isolates as Cronobacter
      malonaticus and one isolate as Cronobacter turicensis.

PMID- 23873392
TI  - Molecule-displacive ferroelectricity in organic supramolecular solids.
AB  - Ferroelectricity is essential to many forms of current technology, ranging from
      sensors and actuators to optical or memory devices. In this circumstance, organic
      ferroelectrics are of particular importance because of their potential
      application in tomorrow's organic devices, and several pure organic
      ferroelectrics have been recently developed. However, some problems, such as
      current leakage and/or low working frequencies, make their application prospects
      especially for ferroelectric memory (FeRAM) not clear. Here, we describe the
      molecule-displacive ferroelectricity of supramolecular adducts of tartaric acid
      and 1,4-diazabicyclo[2.2.2]octane N,N'-dioxide. The adducts show large
      spontaneous polarization, high rectangularity of the ferroelectric hysteresis
      loops even at high operation frequency (10 kHz), and high performance in
      polarization switching up to 1 * 106 times without showing fatigue. It opens
      great perspectives in terms of applications, especially in organic FeRAM.

PMID- 23873393
TI  - Moral orientation and relationships in school and adolescent pro- and antisocial
      behaviors: a multilevel study.
AB  - This multilevel study examined the relationships between moral climate factors
      and prosocial as well as antisocial behaviors inside and outside the school
      (school misconduct, delinquent behavior, and vandalism). The moral climate
      factors were punishment- and victim-based moral orientation, relationships among
      students, and teacher-student relationships. The analyses of data from 670
      students in 69 classes showed that the classroom-level variables only had a
      significant impact on misconduct at school of students aged 12 to 20. For the
      other outcome variables, the student-level variables (student and teacher-student
      relationships, but especially students' moral orientation) were significant. A
      novel finding was that a positive teacher-student relationship not only proved to
      be related to less misconduct inside the school but also to less delinquent
      behavior and vandalism outside the school. This indicates that the teacher is an
      important socializing agent for adolescent behavior in general. 

PMID- 23873394
TI  - Interaction of UV radiation with DNA.

PMID- 23873395
TI  - Ectopic localization of auxin and cytokinin in tobacco seedlings by the plant
      oncogenic AK-6b gene of Agrobacterium tumefaciens AKE10.
AB  - The oncogenic 6b gene of Agrobacterium tumefaciens induces a number of
      morphological and metabolic alterations in plants. Although molecular functions
      associated with the 6b genes have been proposed, including auxin transport, sugar
      transport, transcriptional regulation, and miRNA metabolism, so far an
      unequivocal conclusion has not been obtained. We investigated the association
      between auxin accumulation and tumor development of the tobacco seedlings
      expressing the AK-6b gene under the control of the dexamethasone-inducible
      promoter. Indole-3-acetic acid (IAA) localization was examined by immunochemical
      staining with monoclonal antibody against IAA and by histochemical analysis using
      the IAA-specific induced construct, DR5::GUS (beta-glucuronidase). Both
      procedures indicated that IAA preferentially accumulated in the tumorous
      protrusions as well as in newly developing vascular bundles in the tumors.
      Furthermore, true leaves also showed abaxial IAA localization, leading to altered
      leaves in which the adaxial and abaxial identities were no longer evident. Co
      localization of cytokinin and auxin in the abaxial tumors was verified by
      immunochemical staining with an antibody against cytokinin. Treatment of AK-6b
      seedlings with N-1-naphthylphthalamic acid, an inhibitor of polar auxin
      transport, promoted the morphological severity of phenotypes, whereas 1
      naphthoxyacetic acid, a specific auxin influx carrier inhibitor, induced tumor
      regression on cotyledons and new tumorous proliferations on hypocotyls. Prominent
      accumulation of both auxin and cytokinin was observed in both regressed and newly
      developing tumors. We suggest from these results that modulation of
      auxin/cytokinin localization as a result of AK-6b gene expression is responsible
      for the tumorous proliferation. 

PMID- 23873396
TI  - Diaphragm depth in normal subjects.
AB  - INTRODUCTION: Needle electromyography (EMG) of the diaphragm carries the
      potential risk of pneumothorax. Knowing the approximate depth of the diaphragm
      should increase the test's safety and accuracy. METHODS: Distances from the skin
      to the diaphragm and from the outer surface of the rib to the diaphragm were
      measured using B mode ultrasound in 150 normal subjects. RESULTS: When measured
      at the lower intercostal spaces, diaphragm depth varied between 0.78 and 4.91 cm
      beneath the skin surface and between 0.25 and 1.48 cm below the outer surface of
      the rib. Using linear regression modeling, body mass index (BMI) could be used to
      predict diaphragm depth from the skin to within an average of 1.15 mm.
      CONCLUSIONS: Diaphragm depth from the skin can vary by more than 4 cm. When image
      guidance is not available to enhance accuracy and safety of diaphragm EMG, it is
      possible to reliably predict the depth of the diaphragm based on BMI.

PMID- 23873398
TI  - [Newest developments and assessment of epibulbar glaucoma drainage implants].

PMID- 23873397
TI  - [Tube versus trabeculectomy study].
AB  - Epibulbar glaucoma drainage devices have been only slightly modified since their
      introduction more than 40 years ago. Having been used primarily in only difficult
      cases with a poor prognosis (and therefore with poor clinical results) the
      recently published trabeculectomy versus tube study (TVT) led to a change in our
      understanding of these devices. In this study epibulbar glaucoma drainage devices
      (here the Baerveldt device) were employed for early implantation (in some cases
      as primary glaucoma surgery intervention). Being sceptically monitored the
      results over the first 5 year clearly showed an almost equal or even better
      outcome in comparison to trabeculectomy. Despite these good results a critical
      evaluation seems mandatory mainly because of the unsolved problems concerning
      late complications. Late tube erosion with subsequent blebitis and enophthalmitis
      as well as late base plate encapsulation need to be mentioned here. The latter
      leads to thick fibrous tissue around the base plate resulting in an increase of
      intraocular pressure (IOP). Late corneal decompensation is also a late
      complication the pathomechanism of which is only poorly understood. Solving and
      treating such late complications are often troublesome and time consuming. Future
      experiments should lead to development of new drainage implant designs and the
      bulk material should be enhanced and optimized to increase clinical surgical
      results. 

PMID- 23873399
TI  - [Diffusely margined papilla of unclear origin in a 30-year-old patient].

PMID- 23873401
TI  - Lessons from the Tc-99m shortage: implications of substituting Tl-201 for Tc-99m
      single-photon emission computed tomography.
AB  - BACKGROUND: In 2009, the Chalk River nuclear reactor closed for repairs that led
      to a critical shortage of technetium-99m (Tc-99m). Several centers used thallium
      201 (Tl-201) as an alternative radiotracer for myocardial perfusion imaging.
      Because Tl-201 is considered by many as a suboptimal radiotracer, we sought to
      understand the impact of using Tl-201 (during the Tc-99m shortage) on downstream
      resource utilization. METHODS AND RESULTS: We performed a retrospective study at
      the Ottawa Heart Institute of 7402 patients (60% men; mean age, 62.6 +/- 11.8
      years), patients were referred for myocardial perfusion imaging between May 2008
      and January 2011 (PRE_Tc-99m [2938 patients]), during (DURING_Tl-201 [2959
      patients]), and after (POST_Tc-99m [1505 patients]) the Tc-99m shortage. Patients
      were followed for 6 months after their index myocardial perfusion imaging to
      determine subsequent rates of cardiac catheterization or noninvasive imaging.
      More downstream testing was seen in the Tl-201 cohort (639 [21.4%] patients) than
      the Tc-99m cohort (537 [12.1%] patients; P<0.001). After adjustment using
      propensity scores, differences in downstream referral rates were maintained. The
      downstream investigations resulted in an estimated increase in per-patient costs
      ($165.22; 95% confidence interval, 153.00-177.42) in the DURING_Tl-201 cohort
      compared with the Tc-99m cohort ($90.97; 95% confidence interval, 83.42-98.90;
      P<0.001). As well, the mean effective radiation dose per-patient was higher in
      DURING_Tl-201 (23.57 mSv; 95% confidence interval, 23.16-23.96) than in Tc-99m
      (12.92 mSv; 95% confidence interval, 12.55-13.40; P<0.001). CONCLUSIONS: In this
      single-center study, the use of Tl-201 during the Tc-99m shortage was associated
      with an increase in downstream testing, cost, and patient radiation exposure, but
      these findings may not be generalizable to other centers. Although Tl-201
      provided a short-term solution to the unexpected Tc-99m shortage, long-term cost
      effective solutions should be areas of future study.

PMID- 23873402
TI  - Assessment of mitral valve adaptation with gated cardiac computed tomography:
      validation with three-dimensional echocardiography and mechanistic insight to
      functional mitral regurgitation.
AB  - BACKGROUND: Mitral valve (MV) enlargement is a compensatory mechanism capable of
      preventing functional mitral regurgitation (FMR) in dilated ventricles. Total
      leaflet area and its relation with closure area measured by 3-dimensional (3D)
      echocardiography have been related to FMR. Whether these parameters can be
      assessed with other imaging modalities is not known. Our objectives are to
      compare cardiac computed tomography (CT)-based measurements of MV leaflets with
      3D echocardiography and determine the relationship of these metrics to the
      presence of FMR. METHODS AND RESULTS: We used 2 cohorts of patients who had
      cardiac CT to measure MV total leaflet, closure, and annulus areas. In cohort 1
      (26 patients), we validated these CT metrics to 3D echocardiography. In cohort 2
      (66 patients), we assessed the relation of MV size with the presence of FMR in 3
      populations: heart failure with FMR, heart failure without FMR, and normal
      controls. Cardiac CT and 3D echocardiography produced similar results for total
      leaflet (R(2)=0.97), closure (R(2)=0.89), and annulus areas (R(2)=0.84). MV size
      was the largest in heart failure without FMR compared with controls and patients
      with FMR (9.1 +/- 1.7 versus 7.5 +/- 1.0 versus 8.1 +/- 0.9 cm(2)/m(2); P<0.01).
      Patients with FMR had reduced ratios of total leaflet to closure areas and total
      leaflet to annulus areas when compared with patients without FMR (P<0.01).
      CONCLUSIONS: MV size measured by CT is comparable with 3D echocardiography. MV
      enlargement in cardiomyopathy suggests leaflet adaptation. Patients with FMR have
      inadequate adaptation as reflected by decreased ratios of leaflet area and areas
      determined by ventricle size (annulus and closure areas). These measurements
      provide additional insight into the mechanism of FMR.

PMID- 23873400
TI  - Four decades of leading-edge research in the reproductive and developmental
      sciences: the Infant Primate Research Laboratory at the University of Washington
      National Primate Research Center.
AB  - The Infant Primate Research Laboratory (IPRL) was established in 1970 at the
      University of Washington as a visionary project of Dr. Gene (Jim) P. Sackett.
      Supported by a collaboration between the Washington National Primate Research
      Center and the Center on Human Development and Disability, the IPRL operates
      under the principle that learning more about the causes of abnormal development
      in macaque monkeys will provide important insights into the origins and treatment
      of childhood neurodevelopmental disabilities. Over the past 40 years, a broad
      range of research projects have been conducted at the IPRL. Some have described
      the expression of normative behaviors in nursery-reared macaques while others
      have focused on important biomedical themes in child health and development. This
      article details the unique scientific history of the IPRL and the contributions
      produced by research conducted in the laboratory. Past and present investigations
      have explored the topics of early rearing effects, low-birth-weight, prematurity,
      birth injury, epilepsy, prenatal neurotoxicant exposure, viral infection
      (pediatric HIV), diarrheal disease, vaccine safety, and assisted reproductive
      technologies. Data from these studies have helped advance our understanding of
      both risk and resiliency in primate development. New directions of research at
      the IPRL include the production of transgenic primate models using our embryonic
      stem cell-based technology to better understand and treat heritable forms of
      human intellectual disabilities such as fragile X.

PMID- 23873403
TI  - HbA1c levels in patients with gestational diabetes mellitus: Relationship with
      pre-pregnancy BMI and pregnancy outcome.
AB  - BACKGROUND/AIMS: The use of glycated hemoglobin (HbA1c) measurement in
      gestational diabetes mellitus (GDM) is controversial. Aim of the present study
      was to determine HbA1c levels in a series of GDM patients, in order to verify the
      possible contribution of HbA1c to GDM management. MATERIALS/SUBJECTS AND METHODS:
      The study included 148 caucasian GDM patients. GDM screening was performed
      between the 24th and the 28th week of gestation by a two-step procedure,
      according to the 4th and 5th International Workshop Conference on Gestational
      Diabetes Mellitus recommendations. Exclusion criteria were: preexisting diabetes,
      corticosteroid therapy, history of asthma or hypertension, known fetal anomaly,
      history of previous stillbirth, preterm delivery considered to be likely for
      either maternal disease or fetal conditions. HBA1c was determined by a standard
      HPLC technique. RESULTS: At GDM diagnosis, all HbA1c levels were <= 6% and the
      greatest frequency (71/148; 48.0%) of HbA1c values resulted in the range 5.0
      5.3%. This frequency increased to 54% before delivery. A significant correlation
      between HbA1c values at GDM diagnosis and individual BMI prior to conception was
      observed. The proportion of pregnancies presenting negative outcomes increased
      progressively with increasing HbA1c levels, from 6.2% (1/16) for HbA1c levels <5%
      to 18.3% (13/71) for HbA1c 5.0-5.3%, to 37.8% (17/45) in patients with HBA1c
      levels 5.4-5.6%, to 56.2% (9/16) for HbA1c levels >5.6%. ROC analysis showed that
      HbA1c at diagnosis and before delivery resulted a good predictor of adverse
      pregnancy outcome. CONCLUSIONS: The present results indicate that HbA1c levels
      could be of help in predicting adverse pregnancy events.

PMID- 23873405
TI  - Cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against
      febrile neutropenia in lymphoma patients.
AB  - BACKGROUND: Febrile neutropenia is a serious toxicity of cancer chemotherapy that
      is usually treated in hospital. We assessed the cost-effectiveness of filgrastim
      and pegfilgrastim as primary prophylaxis against febrile neutropenia in diffuse
      large B-cell lymphoma (DLBCL) patients undergoing chemotherapy. METHODS: We used
      a Markov model that followed patients through induction chemotherapy to compare
      the three prophylaxis strategies: 1) no primary prophylaxis against febrile
      neutropenia; 2) primary prophylaxis with 10 days of filgrastim therapy; and 3)
      primary prophylaxis with a single dose of pegfilgrastim. The target population
      was a hypothetical cohort of 64-year-old men and women with DLBCL. Data sources
      included published literature and current clinical practice. The analysis was
      conducted from a publicly funded health-care system perspective. The main outcome
      measures included costs, quality-adjusted life years (QALYs), and incremental
      cost-effectiveness ratios (ICERs). RESULTS: In the base-case analysis, costs
      associated with no primary prophylaxis, primary prophylaxis with 10 days of
      filgrastim, and primary prophylaxis with pegfilgrastim were CaD $7314, CaD
      $13947, and CaD $16290, respectively. The QALYs associated with the three
      strategies were 0.2004, 0.2015, and 0.2024, respectively. The ICER for the
      filgrastim vs no primary prophylaxis strategy was CaD $5796000 per QALY. The ICER
      for the pegfilgrastim vs filgrastim primary prophylaxis strategy was CaD $2611000
      per QALY. All one-way sensitivity analyses yielded ICERs greater than CaD $400000
      per QALY. Cost-effectiveness acceptability curves show that 20.0% of iterations
      are cost-effective at a willingness-to-pay threshold of CaD $1595000 for the
      filgrastim strategy and CaD $561000 for the pegfilgrastim strategy. CONCLUSIONS:
      Primary prophylaxis against febrile neutropenia with either filgrastim or
      pegfilgrastim is not cost-effective in DLBCL patients.

PMID- 23873404
TI  - How can health literacy influence outcomes in heart failure patients? Mechanisms
      and interventions.
AB  - Health literacy is discussed in papers from 25 countries where findings suggest
      that approximately a third up to one half of the people in developed countries
      have low health literacy. Specifically, health literacy is the mechanism by which
      individuals obtain and use health information to make health decisions about
      individual treatments in the home, access care in the community, promote provider
      patient interactions, structure self-care, and navigate health care programs both
      locally and nationally. Further, health literacy is a key determinant of health
      and a critical dimension for assessing individuals' needs, and, importantly,
      their capacity for self-care. Poorer health knowledge/status, more medication
      errors, costs, and higher rates of morbidity, readmissions, emergency room
      visits, and mortality among patients with health illiteracy have been
      demonstrated. Individuals at high risk for low health literacy include the
      elderly, disabled, Blacks, those with a poverty-level income, some or less high
      school education, either no insurance or Medicare or Medicaid, and those for whom
      English is a second language. As a consequence, health literacy is a complex,
      multifaceted, and evolving construct including aspects of social, psychological,
      cultural and economic circumstances. The purpose of this paper is to describe the
      mechanisms and consequences of health illiteracy. Specifically, the prevalence,
      associated demographics, and models of health literacy are described. The
      mechanism of health illiteracy's influence on outcomes in heart failure is
      proposed. Tools for health literacy assessment are described and compared.
      Finally, the health outcomes and general interventions to enhance the health
      outcomes in heart failure are discussed. 

PMID- 23873406
TI  - Primary prophylaxis with hematopoietic colony stimulating factor: insights from a
      Canadian cost-effectiveness analysis.

PMID- 23873407
TI  - Iridium(I)-catalyzed vinylic C-H borylation of 1-cycloalkenecarboxylates with
      bis(pinacolato)diboron.
AB  - Ir(I)-catalyzed C-H borylation of 1-cycloalkenecarboxylic derivatives with
      bis(pinacolato)diboron affords various alkenylboronates with functional groups in
      excellent yields. This reaction was also used in a one-pot borylation/Suzuki
      Miyaura cross-coupling procedure.

PMID- 23873408
TI  - Sialic Acid Receptors of Viruses.
AB  - Sialic acid linked to glycoproteins and gangliosides is used by many viruses as a
      receptor for cell entry. These viruses include important human and animal
      pathogens, such as influenza, parainfluenza, mumps, corona, noro, rota, and DNA
      tumor viruses. Attachment to sialic acid is mediated by receptor binding proteins
      that are constituents of viral envelopes or exposed at the surface of non
      enveloped viruses. Some of these viruses are also equipped with a neuraminidase
      or a sialyl-O-acetyl-esterase. These receptor-destroying enzymes promote virus
      release from infected cells and neutralize sialic acid-containing soluble
      proteins interfering with cell surface binding of the virus. Variations in the
      receptor specificity are important determinants for host range, tissue tropism,
      pathogenicity, and transmissibility of these viruses. 

PMID- 23873409
TI  - Retinal identification based on an Improved Circular Gabor Filter and Scale
      Invariant Feature Transform.
AB  - Retinal identification based on retinal vasculatures in the retina provides the
      most secure and accurate means of authentication among biometrics and has
      primarily been used in combination with access control systems at high security
      facilities. Recently, there has been much interest in retina identification. As
      digital retina images always suffer from deformations, the Scale Invariant
      Feature Transform (SIFT), which is known for its distinctiveness and invariance
      for scale and rotation, has been introduced to retinal based identification.
      However, some shortcomings like the difficulty of feature extraction and
      mismatching exist in SIFT-based identification. To solve these problems, a novel
      preprocessing method based on the Improved Circular Gabor Transform (ICGF) is
      proposed. After further processing by the iterated spatial anisotropic smooth
      method, the number of uninformative SIFT keypoints is decreased dramatically.
      Tested on the VARIA and eight simulated retina databases combining rotation and
      scaling, the developed method presents promising results and shows robustness to
      rotations and scale changes. 

PMID- 23873410
TI  - Observing reduction of 4-nitrobenzenthiol on gold nanoparticles in situ using
      surface-enhanced Raman spectroscopy.
AB  - In this article, reduction of 4-nitrobenzenthiol (4-NBT) on Au nanoparticles
      (NPs) was characterized using surface-enhanced Raman scattering (SERS). Plasmon
      driven chemical transformation from 4-NBT dimering into p,p'-dimercaptoazobenzene
      (DMAB) has been investigated on the surface of Au NPs. The laser power-dependent
      SERS spectra of 4-NBT on the surface of Au substrates were studied, and show that
      the laser power has an influence on the SERS signals of 4-NBT on Au NPs and
      production of DMAB by a plasmon-driven surface-catalyzed chemical reaction tends
      to be much easier under relative high laser power. Furthermore, we have used
      simple and efficient Au substrates (gold NPs with a size around 45 nm) exhibiting
      both catalytic properties and SERS activities to monitor the catalytic reaction
      of surface catalytic reaction process with borohydride solution. The experiments
      prove that the nitro-to-amino group conversion could be completed by borohydride
      at ambient conditions on Au substrates. Illuminated with high laser power, 4-NBT
      molecules and already formed DMAB molecules are further reduced into 4
      aminobenzenthiol (4-ABT) by the addition of borohydride, While with low laser
      power 4-NBT molecules are transformed into 4-ABT with DMAB as the intermediate,
      which proves Au NPs are a mild and promising catalyst. Our studies might be
      helpful in extending the understanding of chemical reactions of 4-NBT and related
      research as well as providing a new strategy synthesis of azo dyes and anilines. 

PMID- 23873411
TI  - Coordination complexes of NbX5 (X = F, Cl) with (N,O)- and (O,O)-donor ligands
      and the first X-ray characterization of a neutral NbF5 adduct.
AB  - A variety of fairly air-stable complexes were prepared by straightforward
      reactions of NbX5 (X = F, Cl) with a series of potential bidentate (N,O)- and
      (O,O)-donor ligands in CH2Cl2. NbF5 reacted with equimolar amounts of 2-[(2,6
      diisopropylphenyl)iminomethyl]phenol (dpimpH) and 2-benzoyl-6-hydroxy-6
      phenylpentafulvene (bhpfH) to afford the mononuclear complexes NbF5[kappa(1)(O)
      OC6H4CH=NHC6H3(CHMe2)2], 2, and NbF5[kappa(1)(O)-bhpfH], 7, respectively. The 1:1
      reactions of NbF5 with salicylaldehyde oxime (saoH2) and 2-phenylaminoethanol
      gave the hexafluoroniobato salts [NbF4{kappa(1)(O)-ON(H)=CHC6H4OH}2][NbF6], 3,
      and [NbF4{kappa(1)(O)-OCH2CH2NH2Ph}2][NbF6], 6, respectively. The syntheses of 2,
      3 and 6 are accompanied by oxygen to nitrogen intramolecular H migration, leading
      to the formation of metal-alkoxide moieties. The parallel chemistry of NbCl5 is
      characterised by HCl release. The 1:1 reactions with dpimpH, saoH2 and bhpfH
      yielded, respectively, the ionic complex [NbCl2{kappa(1)(N):kappa(1)(O)
      dpimp}2][NbCl6], 4a, the neutral-dinuclear Nb2Cl7[kappa(1)(O)-saoH][kappa(2)(O)
      sao], 5, and the mononuclear NbCl4[kappa(2)(O)-bhpf], 8. The tantalum species
      [TaCl2{kappa(1)(N):kappa(1)(O)-dpimp}2][TaCl6], 4b, was prepared from
      TaCl5/dpimpH. The new products 2-8 were fully characterized by analytical and
      spectroscopic techniques. Moreover the solid state structures of 2 and 8 were
      ascertained by X-ray diffraction studies; the structure of 2 exhibits an
      intramolecular bifurcated N-H...(O,F) hydrogen bond. DFT calculations were
      carried out in order to predict the lowest energy structures in the distinct
      cases, showing generally good agreement with the experimental data.

PMID- 23873412
TI  - Solvent effect and reactivity trend in the aerobic oxidation of 1,3-propanediols
      over gold supported on titania: NMR diffusion and relaxation studies.
AB  - In recent work, it was reported that changes in solvent composition, precisely
      the addition of water, significantly inhibits the catalytic activity of Au/TiO2
      catalyst in the aerobic oxidation of 1,4-butanediol in methanol due to changes in
      diffusion and adsorption properties of the reactant. In order to understand
      whether the inhibition mechanism of water on diol oxidation in methanol is
      generally valid, the solvent effect on the aerobic catalytic oxidation of 1,3
      propanediol and its two methyl-substituted homologues, 2-methyl-1,3-propanediol
      and 2,2-dimethyl-1,3-propanediol, over a Au/TiO2 catalyst has been studied here
      using conventional catalytic reaction monitoring in combination with pulsed-field
      gradient nuclear magnetic resonance (PFG-NMR) diffusion and NMR relaxation time
      measurements. Diol conversion is significantly lower when water is present in the
      initial diol/methanol mixture. A reactivity trend within the group of diols was
      also observed. Combined NMR diffusion and relaxation time measurements suggest
      that molecular diffusion and, in particular, the relative strength of diol
      adsorption, are important factors in determining the conversion. These results
      highlight NMR diffusion and relaxation techniques as novel, non-invasive
      characterisation tools for catalytic materials, which complement conventional
      reaction data. 

PMID- 23873413
TI  - Lisinopril dihydrate: single-crystal x-ray structure and physicochemical
      characterization of derived solid forms.
AB  - Screening for new solid forms of the antihypertensive lisinopril was performed by
      recrystallization of the commercial form, lisinopril dihydrate, from various
      solvents and by exposing the product of its dehydration to a series of vapors
      under controlled conditions. Modifications other than the dihydrate encountered
      in the study included new anhydrous and amorphous forms, with intrinsic
      dissolution rates significantly greater than that of the dihydrate. Further
      physicochemical characterization included constant and programmed temperature
      powder X-ray diffraction, differential scanning calorimetry, thermogravimetry,
      and Fourier transform infrared spectroscopy. In the course of this study, the
      single-crystal X-ray structure of lisinopril dihydrate, [a = 14.550(2), b =
      5.8917(8), c = 14.238(2) A, beta = 112.832(3) degrees  at T = 173(2) K, space
      group P21 , Z = 2], was determined for the first time, revealing its double
      zwitterionic character in the solid state.

PMID- 23873415
TI  - Development of HPLC/fluorescence detection method for chiral resolution of
      dansylated benzimidazoles derivatives.
AB  - The development of high performance liquid chromatography method on amylose-based
      stationary phase (Chiralpak AD) with n-hexane-2-propanol (90:10, v/v) as mobile
      phase allowed the enantioseparation of non-dansylated and dansylated
      benzimidazole derivatives, prepared from potent-AMPK activators, to be achieved.
      Using both fluorescence and ultraviolet detection, limits of detection and
      quantification were determined. Fluorescence detection seems to be the most
      appropriate technique since the first enantiomer of dansylated benzimidazole 8
      eluted with a limit of quantification of 2.25 nm. The quantification limit was
      improved 10-fold by fluorescence detection compared with a previous report
      describing mass spectrometry detection. Linearity and repeatability parameters
      were validated. These lower limits obtained by fluorescence detection, associated
      with good resolution observed for the dansylated derivatives, make this chiral
      methodology convenient for the use of these fluorescent potent-AMPK activators as
      probes to elucidate their cellular localization and their mechanism of action.

PMID- 23873414
TI  - The GreenCut: re-evaluation of physiological role of previously studied proteins
      and potential novel protein functions.
AB  - Based on comparative genomics, a list of proteins present in the green algal,
      flowering and nonflowering plant lineages, but not detected in nonphotosynthetic
      organisms, was assembled (Merchant et al., Science 318:245-250, 2007; Karpowicz
      et al., J Biol Chem 286:21427-21439, 2011). This protein grouping, previously
      designated the GreenCut, was established using stringent comparative genomic
      criteria; they are those Chlamydomonas reinhardtii proteins with orthologs in
      Arabidopsis thaliana, Physcomitrella patens, Oryza sativa, Populus tricocarpa and
      at least one of the three Ostreococcus species with fully sequenced genomes, but
      not in bacteria, yeast, fungi or mammals. Many GreenCut proteins are also present
      in red algae and diatoms and a subset of 189 have been identified as encoded on
      nearly all cyanobacterial genomes. Of the current GreenCut proteins (597 in
      total), approximately half have been studied previously. The functions or
      activities of a number of these proteins have been deduced from phenotypic
      analyses of mutants (defective for genes encoding specific GreenCut proteins) of
      A. thaliana, and in many cases the assigned functions do not exist in C.
      reinhardtii. Therefore, precise physiological functions of several previously
      studied GreenCut proteins are still not clear. The GreenCut also contains a
      number of proteins with certain conserved domains. Three of the most highly
      conserved domains are the FK506 binding, cyclophilin and PAP fibrillin domains;
      most members of these gene families are not well characterized. In general, our
      analysis of the GreenCut indicates that many processes critical to green lineage
      organisms remain unstudied or poorly characterized. We have begun to examine the
      functions of some GreenCut proteins in detail. For example, our work on the
      CPLD38 protein has demonstrated that it has an essential role in photosynthetic
      function and the stability of the cytochrome b 6 f complex. 

PMID- 23873416
TI  - Polymorphism of UBC9 gene encoding the SUMO-E2-conjugating enzyme and breast
      cancer risk.
AB  - UBC9 protein (E2-conjugating enzyme) plays a key role in post-translation
      modification named sumoylation. Proteins, which are sumoylated take part in many
      cellular processes including cell growth, maintaining the genome integrity and
      stability and cancer development. The aim of this study was to investigate an
      association between three polymorphisms of the UBC9 gene: c.73G>A (rs11553473),
      c.430T>G (rs75020906) and g.1289209T>C (rs7187167) and a risk of ductal breast
      cancer occurrence. We performed a case-control study in 181 breast cancer cases
      and 277 controls using PCR-RLFP and ASO-PCR. In the case of the 430T>G
      polymorphism of the UBC9 gene lack of variability suggests that there is not a
      polymorphic site in polish population. We observed that a risk of breast cancer
      occurrence is elevated in patients with the G/A genotype (OR 5.03; 95% Cl 3.05
      8.28), the A/A genotype (OR 11.3; 95% Cl 4.24-30.3) and the A allele (OR 6.86;
      95% Cl 4.43-10.6) of the c.73G>A polymorphism. In the case of the g.1289209T>C
      polymorphism we found a correlation between estrogen receptor (ER) expression and
      the T/T genotype (OR 0.22; 95% Cl 0.07-0.64) and the T allele (OR 0.53; 95% Cl
      0.32-0.88). We also found a correlation between the T/T genotype (OR 4.13; 95% Cl
      1.21-14.1) and the T allele (OR 2.09; 95% Cl 1.07-4.08) of the g.1289209T>C
      polymorphism with triple negative breast cancer. Our results suggest that the
      variability of the UBC9 gene can play a role in breast cancer occurrence.

PMID- 23873417
TI  - Effectiveness of varenicline versus nicotine replacement therapy for smoking
      cessation with minimal professional support: evidence from an English population
      study.
AB  - RATIONALE: Limited evidence from randomised controlled trials suggests that
      varenicline might be more effective than nicotine replacement therapy (NRT) in
      achieving abstinence from smoking. The comparative effectiveness of varenicline
      when prescribed under routine circumstances and in the general population has not
      been tested. OBJECTIVES: To compare the abstinence rates of smokers trying to
      stop having used varenicline vs. NRT on prescription (Rx) when provided with
      minimal professional support in the general population while adjusting for key
      potential confounders. METHODS: A large survey of a representative sample of the
      English population. Participants were 1,579 adults who smoked within the previous
      12 months and made at least one quit attempt with varenicline or NRT Rx in their
      most recent quit attempt. The main outcome measure was self-reported abstinence
      up to the time of the survey, adjusted for key potential confounders including
      urges to smoke. A sensitivity analysis was conducted in subsamples in which the
      quit attempt started up to 6 months or more than 6 months ago. RESULTS: The
      adjusted odds of abstinence in users of varenicline were 1.76 (95 % CI = 1.22
      2.53) times higher compared with users of NRT Rx. However, there was no
      detectable difference in the subsample of smokers who started their quit attempt
      more than 6 months ago (adjusted OR = 1.03, 95 %CI = 0.54-1.96). CONCLUSIONS:
      Varenicline use with minimal professional support in the general population of
      smokers appears more effective than NRT Rx in achieving short-term abstinence.
      However, this effect may disappear in the long-term. Research is needed to
      confirm this and establish what may underlie it.

PMID- 23873419
TI  - Safety and efficiency of treatment with cinacalcet of haemodialysed patients with
      chronic kidney disease and secondary hyperparathyroidism.
AB  - INTRODUCTION: Secondary hyperparathyroidism (sHPT) is a common disorder in
      haemodialysed patients with chronic kidney disease (CKD). Cinacalcet increases
      the sensitivity of calcium receptor to the serum calcium, thus reducing serum
      parathormone (PTH) concentration. The aim of this study was to assess the safety
      and efficacy of six-month treatment with cinacalcet in haemodialysed CKD patients
      with sHPT in upper Silesia. MATERIAL AND METHODS: 71 haemodialysed CKD patients
      with sHPT (PTH > 300 pg/mL) were enrolled in this study. The target was to
      decrease PTH concentration below 300 pg/mL. PTH (ECL; Roche, Mannheim, Germany),
      calcium and phosphate concentration was assessed before the first dose of
      cinacalcet and then after three and six months of treatment, before haemodialysis
      session. The results are shown as means and 95% confidence index. RESULTS: 58
      patients completed the study. There was a significant decrease in serum PTH
      concentration from 1,138 pg/mL (931-1,345 pg/mL) to 772 pg/mL (551-992 pg/mL)
      after three months of treatment (p < 0.0001) and to 635 pg/mL (430-839 pg/mL; p <
      0.0001) after six months. The target PTH concentration was reached in 25% of the
      patients after three months and in 45% after six months of treatment. Cinacalcet
      was ineffective in decreasing serum PTH in 16 (28%) patients. There were no
      significant differences in serum calcium and phosphate concentration during the
      observation period. CONCLUSIONS: 1. Cinacalcet decreases serum PTH concentration
      in most haemodialysed CKD patients with sHPT. 2. In 28% of patients, resistance
      to treatment with cinacalcet was observed. 3. Cinacalcet treatment was well
      tolerated and caused only a few side effects.

PMID- 23873418
TI  - Involvement of amygdalar protein kinase A, but not calcium/calmodulin-dependent
      protein kinase II, in the reconsolidation of cocaine-related contextual memories
      in rats.
AB  - RATIONALE: Contextual control over drug relapse depends on the successful
      reconsolidation and retention of context-response-cocaine associations in long
      term memory stores. The basolateral amygdala (BLA) plays a critical role in
      cocaine memory reconsolidation and subsequent drug context-induced cocaine
      seeking behavior; however, less is known about the cellular mechanisms of this
      phenomenon. OBJECTIVES: The present study evaluated the hypothesis that protein
      kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII)
      activation in the BLA is necessary for the reconsolidation of context-response
      cocaine memories that promote subsequent drug context-induced cocaine-seeking
      behavior. METHODS: Rats were trained to lever-press for cocaine infusions in a
      distinct context, followed by extinction training in a different context. Rats
      were then briefly re-exposed to the previously cocaine-paired context or an
      unpaired context in order to reactivate cocaine-related contextual memories and
      initiate their reconsolidation or to provide a similar behavioral experience
      without explicit cocaine-related memory reactivation, respectively. Immediately
      after this session, rats received bilateral microinfusions of vehicle, the PKA
      inhibitor, Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt
      (Rp-cAMPS), or the CaMKII inhibitor, KN-93, into the BLA or the posterior caudate
      putamen (anatomical control region). Rats were then tested for cocaine-seeking
      behavior (responses on the previously cocaine-paired lever) in the cocaine-paired
      context and the extinction context. RESULTS: Intra-BLA infusion of Rp-cAMPS, but
      not KN-93, following cocaine memory reconsolidation impaired subsequent cocaine
      seeking behavior in a dose-dependent, site-specific, and memory reactivation
      dependent fashion. CONCLUSIONS: PKA, but not CaMKII, activation in the BLA is
      critical for cocaine memory re-stabilization processes that facilitate subsequent
      drug context-induced instrumental cocaine-seeking behavior.

PMID- 23873420
TI  - Determining the enzymatic activities of iodothyronine 5'-deiodinases in renal
      medulla and cortex.
AB  - INTRODUCTION: Thyroid hormone disorders in patients with chronic kidney disease
      (CKD) are a result of impaired conversion of T4 to T3. The importance of kidneys
      in thyroid hormones conversion is not fully understood. The activities of
      different types of iodothyronine deiodinases in the kidney structures have not
      been determined yet. The aim of this study was to determine the activity of
      deiodinase type 1 (D1) and type 2 (D2) in renal cortex and medulla in renal
      cancer patients. MATERIAL AND METHODS: Samples of renal cortex and medulla (ten
      patients) or renal cortex alone (13 patients) were taken from kidneys resected
      because of malignant cancer, from a site opposite to the cancer. Resections were
      performed in the 23 patients (seven female and 16 male) who were 52-82 years old.
      The material was stored at -72 oC. RESULTS: Activity of D1 in renal cortex was
      3.785 +/- 2.041 fmol 125I/mg protein/minute and activity of D2 was 0.236 +/-
      0.125 fmol 125I/mg protein/minute. There was a strong positive correlation
      between D1 and D2 activities in renal cortex (r = 0.890, p < 0.001). Activity of
      D1 in renal medulla was 2.157 +/- 2.176 fmol 125I/mg protein/minute, and activity
      of D2 was 0.168 +/- 0.095 fmol 125I/mg protein/minute. A positive correlation
      between D1 and D2 in renal medulla (r = 0.661, p = 0.038) was observed as well.
      Activities of D1 in cortex and medulla were strongly and positively associated (r
      = 0.794, p = 0.006), whereas there was no correlation between the activities of
      D2 in cortex and medulla (r = 0.224, p = 0.553). CONCLUSIONS: Results presented
      in this study suggest that both cortical and medullary D1 and D2 may be involved
      in thyroid hormone metabolism. This finding could be of clinical relevance in
      patients with impaired renal function.

PMID- 23873421
TI  - Subclinical Cushing's syndrome in adrenal incidentalomas--possible metabolic
      consequences.
AB  - INTRODUCTION: The presence of subclinical Cushing's syndrome (SCS) and some
      features of the metabolic syndrome were evaluated in adrenal incidentaloma
      patients. MATERIAL AND METHODS: 165 patients were studied. Plasma cortisol, ACTH,
      DHEA-S, 17-OH-P, aldosterone, renin activity and 24-h urinary
      methoxycatecholamines were measured. Fasting concentrations of glucose, insulin,
      triglycerides, T-chol., HDL-chol. and LDL-chol. were determined and the FIRI and
      QUICKI indices were calculated. Blood pressure, WHR and BMI were determined in
      all patients. Forty healthy volunteers were the controls. RESULTS: 133 patients
      had unchanged endocrine function, 32 demonstrated hormonal disturbances without
      clinical symptoms (in 26 nonclinical hypercortisolism). The WHR and blood
      pressure in the SCS group were significantly higher than in the patients with
      nonfunctioning adenoma (NA). T-chol and LDL-chol were significantly higher, but
      HDL-chol was significantly lower, in the SCS than in the NA patients. Fasting
      insulin level was significantly higher in the SCS than in the NA patients and
      controls, while fasting glucose level was comparable. QUICKI was significantly
      lower in the SCS and NA patients than in the controls, while FIRI was
      significantly higher in the SCS group. CONCLUSIONS: In incidentaloma patients,
      hormonal function of the adrenal gland should be estimated because some of them
      present subclinical hyperfunction. These patients frequently display features of
      metabolic syndrome such as insulin resistance, hypertension, high triglycerides,
      T-chol and LDL-chol levels. Subtle autonomous cortisol secretion may be the cause
      of these features.

PMID- 23873422
TI  - Pheochromocytoma--analysis of 15 consecutive cases from one centre.
AB  - INTRODUCTION: Pheochromocytoma is a rare tumour, but one of great clinical
      importance as a risk factor of malignancy, cardiovascular diseases and sudden
      death. MATERIAL AND METHODS: 15 consecutive patients (eight women and seven men)
      were hospitalised and submitted for adrenalectomy with pheochromocytoma confirmed
      by histopathologic examination. Adrenalectomies were performed laparoscopically
      in 14 cases (93.3%): in nine by the retroperitoneal posterior mode and in five by
      the transperitoneal lateral approach. RESULTS: Molecular-genetic examination of
      VHL, RET, SDHB, SDHC and SDHD genes revealed inherited predisposition for PHEO in
      three of 15 patients (20%): RET mutations typical for MEN 2a in two patients and
      VHL mutation in one patient. Disturbances of the carbohydrate metabolism occurred
      in nine patients (60%). Ten patients (66%) reported paroxysmal symptoms. In all
      cases, with the exception of a von Hippel-Lindau patient, density of tumours
      exceeded 20 HU. In all studied patients, urine concentration of normetanephrines
      exceeded their normal range and greatly prevailed over metanephrines values,
      which were increased in six of them (40%). CONCLUSIONS: Urine
      metoxycatecholamines and increased tissue density are sufficient in
      pheochromocytoma detection. However, taking into account clinical and
      supplemental biochemical data may be helpful in the diagnostic process.
      Laparoscopic adrenalectomy is a fully sufficient and safe method of
      pheochromocytoma excision.

PMID- 23873423
TI  - Serum sex hormone binding globulin profile and its association with insulin
      resistance in Chinese peri-menopausal women.
AB  - INTRODUCTION: The aim of this study was to measure serum sex hormone binding
      globulin (SHBG) profile in Chinese peri-menopausal women, and assess its
      correlation with insulin resistance (IR)-related parameter, namely HOMA-IR, in
      this special population. MATERIAL AND METHODS: A cross-sectional study by the
      method of cluster sampling was performed in 1,827 women, who were in hospital for
      routine check-up. Serum SHBG profile and anthropometric indices of hormonal,
      adiposity, and metabolic variables were measured. According to their age and
      menstruation status, the subjects were divided into three groups: pre-menopause
      group, peri-menopause group, and post-menopause group. RESULTS: Serum SHBG level
      was found to be negatively correlated with BMI in all groups and to increase in
      parallel with age in women of reproductive age. However, independently of age, it
      significantly increased from the onset of menopause transition, and slightly
      declined after menopause. After adjustment for age and BMI, HOMA-IR in peri
      menopausal women was closely related only to SHBG. SHBG level was found to be the
      only independent significant determinant of HOMA-IR. On the basis of ROC curve
      analysis for the prediction of insulin resistance using HOMA-IR value, AUC for
      SHBG reached a value of 0.816 (0.636-0.996, 95% confidence interval). The best
      cutoff value that discriminates peri-menopausal women with or without insulin
      resistance is 41.73 nmol/L, with a sensitivity of 81.4% and a specificity of
      87.5%. CONCLUSIONS: Low SHBG level may be an independent risk factor of insulin
      resistance in Chinese peri-menopausal women.

PMID- 23873424
TI  - Anti-Mullerian hormone dynamics during ovulation induction treatment with
      recombinant follicle-stimulating hormone in women with polycystic ovary syndrome.
AB  - INTRODUCTION: Anti-Mullerian hormone (AMH) has been suggested as a predictor of
      ovarian response to ovulation induction and controlled ovarian hyperstimulation.
      MATERIAL AND METHODS: Twenty-six women, wishing to become pregnant and who showed
      resistance to clomiphene citrate, were included in the study. All women received
      recombinant follicle-stimulating hormone (recFSH). RESULTS: In the group of good
      responders, luteinising hormone (LH) and oestradiol levels were lower than in the
      group of non-responders. Free testosterone levels, free androgen index, and
      insulin resistance were higher in the group of non-responders. In the group of
      good responders, AMH levels decreased on successive days of ovarian stimulation
      and a greater slope of AMH levels was observed in patients with a higher number
      of increasing follicles. PCOS patients have low FSH and high AMH levels. It could
      be suggested that the serum AMH decrease preceded growth of many follicles, which
      is a consequence of the FSH stimulation. In anovulatory PCOS women, gently
      increasing the serum FSH level reduces the AMH excess, thus relieving the
      inhibition from the latter on aromatase expression by selectable follicles and
      allowing the emergence of growing follicles. Patients with severe
      hyperandrogenism, insulin resistance and high level of LH do not respond to
      stimulation. CONCLUSIONS: The decrease of AMH levels in PCOS women after one week
      of ovarian stimulation is a practical, valuable indicator which could predict the
      patients with a high risk of ovarian hyperstimulation. Anovulating PCOS patients
      with severe hyperandrogenism, insulin resistance and hyperinsulinaemia should not
      be qualified for recFSH ovarian stimulation.

PMID- 23873426
TI  - Acute respiratory failure in goitre patients qualified for operative treatment.
AB  - INTRODUCTION: To present a clinical picture and management of goitre patients
      with acute respiratory failure. MATERIAL AND METHODS: A total of 7,356 patients
      were operated on between 2000 and 2011 for various goitres, including 1,214
      (16.5%) retrosternal or mediastinal types. Eight (0.1%) patients (six women and
      two men aged 61-84, mean 76.9 years) presented with acute respiratory failure on
      admission. Seven patients were intubated on admission, and one showed severe
      dyspnoea at rest accompanied by symptoms of peripheral cyanosis. RESULTS: Giant
      retrosternal goitres were found in the eight operated patients. In two cases, the
      goitre was recurrent in character, and another two patients had previously
      suffered from hyperthyroidism (one treated pharmacologically, and one using
      J131). X-ray examination revealed tracheostenosis in all patients. No disorders
      in thyroid function was observed. Preoperative unilateral paralysis of laryngeal
      recurrent nerve was found in three patients. The operations were considered as
      most urgent. Four goitres were neoplastic: two were anaplastic carcinoma, one was
      follicular cell carcinoma and one was squamous cell carcinoma. These patients
      received partial resection to enable reduction of the goitre mass. In three
      patients, tracheostomy was necessary. On the other hand, four patients with non
      malignant goitres underwent complete resection (one patient), nearly complete
      resection (two), and complete resection of one lobe and partial resection of the
      other (one). Three patients required mechanical ventilation postoperatively. Two
      of them, referred to the Intensive Therapy Unit, died from acute circulatory
      failure on day 6 and day 10 postoperatively. The rest were discharged in good
      general condition. CONCLUSIONS: 1. Acute respiratory failure caused by a giant
      goitre is a life-threatening condition that almost always requires an emergency
      intubation. 2. Due to a high risk of complications and high mortality, patients
      with acute respiratory failure caused by giant goitres should be operated in
      hospitals that are very experienced not only in thyroid but also in mediastinal
      surgery.

PMID- 23873425
TI  - Pendrin expression in nodular and non-nodular thyroid tissues.
AB  - INTRODUCTION: Different mechanisms for the expression of pendrin which is an
      apical iodide transporter have been reported in nodular thyroid tissues compared
      to normal thyroid. The aim of the present study was to determine the alterations
      of pendrin expression in nodular and surrounding non-nodular thyroid tissues and
      clarify the role of pendrin in the functional behaviour of nodular lesions.
      MATERIAL AND METHODS: Twenty-six nodular and paired non-nodular normal thyroid
      tissues were collected at the same centre. Patients were divided into two groups
      based on the function of the dominant thyroid nodule; hot nodules (n = 18) and
      cold nodules (n = 8). mRNA levels of pendrin were evaluated by quantitative RT
      PCR. Pendrin protein expression was determined by immunohistochemical analysis.
      Results of dominant nodules were compared to non-nodular thyroid tissue of the
      same patient. RESULTS: No statistically significant difference was found with
      respect to qualitative and quantitative measurements of pendrin expression
      between hot and cold nodules. However, percent immunohistochemical staining of
      pendrin was significantly higher in both hot and cold nodules compared to non
      nodular thyroid tissue of the same patients. RT-PCR revealed comparable mRNA
      levels of pendrin gene between hot nodules and corresponding normal thyroid
      tissues. However, in cold nodules, significantly decreased mRNA levels of pendrin
      were observed compared to normal thyroid tissue. mRNA levels of pendrin showed
      significant positive correlation with TSH in corresponding non-nodular thyroid
      tissues. CONCLUSIONS: The present study demonstrates that expression of pendrin
      could not be influenced by TSH in thyroid nodules and expression level of pendrin
      seems not to have an effect on nodule function.

PMID- 23873427
TI  - Changes of plasma fibroblast growth factor-21 (FGF-21) in oral glucose tolerance
      test and effects of metformin on FGF-21 levels in type 2 diabetes mellitus.
AB  - INTRODUCTION: The objectives of our study were to investigate whether fibroblast
      growth factor-21 (FGF-21) is involved in short-term regulation of glucose and the
      change of FGF-21 after metformin use in diabetic subjects. MATERIAL AND METHODS:
      43 subjects were recruited in the study, including 27 new-onset type 2 diabetes
      patients (nT2DM). A 75 g oral glucose tolerance test (OGTT) was administered to
      them. Blood samples were taken at 0, 60 ,120 and 180 minute of OGTT. nT2DM
      subjects were invited for further investigation, metformin was administered in a
      dose of 1.0 g every day for 1 week. RESULTS: Plasma FGF-21 changed significantly
      in the nT2DM group during the OGTT administration but not in the control group.
      No gender differences were observed at different time points in FGF-21 levels (p
      < 0.05). Administration of metformin for nT2DM resulted in a significant decrease
      in both glucose and FGF-21 at all OGTT times and in insulin at 60 min and 180
      min, indicative of a decrease in HOMA-IR. CONCLUSION: FGF-21 does not seem to be
      involved in short-term regulation of glycaemia in human subjects, and the change
      in OGTT delayed in T2DM. FGF-21 may participate in the processing of metformin,
      improving glucose and insulin sensitivity.

PMID- 23873428
TI  - Adipokines in the pathogenesis of idiopathic inflammatory bowel disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are the two common forms of
      idiopathic inflammatory bowel disease (IBD). The aetiology and pathogenesis of
      IBD are not yet known. Genetic predisposition has been suggested as playing a
      role in the improper immune response to commensal microbiota. The main link of
      IBD pathogenesis is an intestinal immune system disability after enteric
      infection, resulting in an uncontrolled and chronic inflammatory state. Recently,
      numerous studies have been focused on the role of proinflammatory cytokines as
      well as hormones of adipose tissue named adipokines in the pathogenesis of IBD.
      Adipokines have pro- and anti-inflammatory properties and can modulate the immune
      response. It has been shown that obesity is associated with systemic
      microinflammation. On the other hand, experimental studies have revealed a link
      between levels of some adipokines and the severity of inflammation in IBD
      independent of body mass. The fat deposits called 'wrapping' or 'creeping' fat
      envelop the intestine, and adipokines produced by this tissue play an important
      role in the pathogenesis of IBD. The aim of this manuscript was to review the
      current literature concerning the role of adipokines in the pathogenesis of IBD.

PMID- 23873429
TI  - Recurrent acute suppurative thyroiditis due to pyriform sinus fistula in an adult
      -case report.
AB  - We present a case study of acute suppurative thyroiditis (AST) with frequent
      recurrence due to anatomical malformation described as pyriform sinus fistula
      (PSF). Difficulty in diagnosis and treatment may be explained by the rarity of
      the disease in adult patients. AST had been observed in our patient five times
      before a radical surgery treatment was performed. The most typical symptoms and
      signs in our patient include: fever, difficulty in swallowing and tender tumour
      in the left side of the neck. Computed tomography (CT), barium swallow study and
      endoscopic examination gave us an opportunity to confirm the presence of an
      anatomical abnormality. After fistulectomy, we have not observed AST up to the
      date of this publication.

PMID- 23873430
TI  - Can we accurately measure the concentration of clinically relevant vitamin D
      metabolites in the circulation? The problems and their consequences.
AB  - Increased interest in vitamin D measurements in clinical studies has contributed
      to the development in recent years of several new immunochemical assays (manual
      and for automatic analyzers). New methods, including HPLC (high performance
      liquid chromatography), and LC-MS/MS (liquid chromatography coupled with tandem
      mass spectrometry) have also been introduced into routine diagnostic
      laboratories. Because of the variety of assays and methods used, the question
      arises which one is the most accurate for the measurement of vitamin D
      metabolites concentration. In this review, we summarise the advantages and
      disadvantages of these methods, describe the complexity of vitamin D metabolites
      pattern in the circulation, and discuss the problem of accurate measuring its
      concentration.

PMID- 23873431
TI  - Sporadic late onset nemaline myopathy and immunoglobulin deposition disease.
AB  - INTRODUCTION: In monoclonal gammopathy, organ dysfunction can occur due to
      deposition of immunoglobulin fragments. A rare form of acquired myopathy often
      associated with monoclonal gammopathy is sporadic late onset nemaline myopathy
      (SLONM), which is characterized by nemaline rods in myofibers. The pathogenetic
      link between monoclonal gammopathy and SLONM has not yet been elucidated.
      METHODS: Case report of a patient with monoclonal gammopathy who developed a
      progressive myopathy, finally diagnosed as SLONM. RESULTS: A muscle biopsy showed
      mild myopathic changes. A second biopsy 1 year after clinical onset demonstrated
      deposition of immunoglobulin light and heavy chains and the presence of nemaline
      rods. The patient experienced marked improvement of muscle strength after
      autologous stem cell transplantation and treatment with bortezomib, a therapy
      that is known to be effective in light chain deposition disease. CONCLUSIONS: We
      speculate that deposition of light and heavy chains, rather than nemaline bodies,
      has myotoxic effects on skeletal muscle.

PMID- 23873432
TI  - Survival in systemic lupus erythematosus, 1995-2010. A prospective study in a
      Danish community.
AB  - OBJECTIVE: The objective of this paper is to investigate survival and causes of
      death in a Danish lupus population. METHODS: Two hundred and fifteen SLE patients
      (94% Caucasians) were followed prospectively for up to 16 years. Thirty-eight
      patients died. Survival rate and causes of death were analysed. RESULTS: Overall
      standardized mortality ratio (SMR) was 2.2. Peak values were recorded for
      patients aged 20-29 (SMR 21.1). Cumulated survival rates at one, five, 10 and 15
      years were 98.6%, 93.6%, 86.5% and 73.0%, respectively. The most common causes of
      death were cardiovascular events (32%), respiratory system disease (16%) and
      malignancies (13%). Deaths due to infections and active SLE were rare and
      predominated within the first seven years after diagnosis and before age 40,
      while cardiovascular deaths prevailed after 20 years' follow-up. CONCLUSION: This
      study shows that despite progress in lupus management, including direct access to
      specialized hospital care and increased use of hydroxychloroquine, mortality in
      lupus patients is still increased. Main causes of death were active disease and
      infections among the young and newly diagnosed, while cardiovascular deaths
      prevailed in longstanding disease.

PMID- 23873433
TI  - Effects of strategy sequences and response-stimulus intervals on children's
      strategy selection and strategy execution: a study in computational estimation.
AB  - The present study investigates how children's better strategy selection and
      strategy execution on a given problem are influenced by which strategy was used
      on the immediately preceding problem and by the duration between their answer to
      the previous problem and current problem display. These goals are pursued in the
      context of an arithmetic problem solving task. Third and fifth graders were asked
      to select the better strategy to find estimates to two-digit addition problems
      like 36 + 78. On each problem, children could choose rounding-down (i.e.,
      rounding both operands down to the closest smaller decades, like doing 40 + 60 to
      solve 42 + 67) or rounding-up strategies (i.e., rounding both operands up to the
      closest larger decades, like doing 50 + 70 to solve 42 + 67). Children were
      tested under a short RSI condition (i.e., the next problem was displayed 900 ms
      after participants' answer) or under a long RSI condition (i.e., the next problem
      was displayed 1,900 ms after participants' answer). Results showed that both
      strategy selection (e.g., children selected the better strategy more often under
      long RSI condition and after selecting the poorer strategy on the immediately
      preceding problem) and strategy execution (e.g., children executed strategy more
      efficiently under long RSI condition and were slower when switching strategy over
      two consecutive problems) were influenced by RSI and which strategy was used on
      the immediately preceding problem. Moreover, data showed age-related changes in
      effects of RSI and strategy sequence on mean percent better strategy selection
      and on strategy performance. The present findings have important theoretical and
      empirical implications for our understanding of general and specific processes
      involved in strategy selection, strategy execution, and strategic development. 

PMID- 23873434
TI  - A test of the embodied simulation theory of object perception: potentiation of
      responses to artifacts and animals.
AB  - Theories of embodied object representation predict a tight association between
      sensorimotor processes and visual processing of manipulable objects. Previous
      research has shown that object handles can 'potentiate' a manual response (i.e.,
      button press) to a congruent location. This potentiation effect is taken as
      evidence that objects automatically evoke sensorimotor simulations in response to
      the visual presentation of manipulable objects. In the present series of
      experiments, we investigated a critical prediction of the theory of embodied
      object representations that potentiation effects should be observed with
      manipulable artifacts but not non-manipulable animals. In four experiments we
      show that (a) potentiation effects are observed with animals and artifacts; (b)
      potentiation effects depend on the absolute size of the objects and (c) task
      context influences the presence/absence of potentiation effects. We conclude that
      potentiation effects do not provide evidence for embodied object representations,
      but are suggestive of a more general stimulus-response compatibility effect that
      may depend on the distribution of attention to different object features. 

PMID- 23873435
TI  - The impact of fear words in a secondary task on complex motor performance: a dual
      task climbing study.
AB  - The relationship between emotion and motor action has been previously examined
      using relatively simple motor tasks. However, there has been limited research
      using more complex physical tasks. One such complex physical task is high-angle
      climbing. In this experiment, we examined the performance of climbers in a dual
      climbing and word memory task, in which they were asked to recall fear-related or
      neutral words after the climb, as well as single-task performance. Climbing
      distance, efficiency, and word recall all significantly decreased in the dual
      task conditions, relative to the single tasks. Climbing distance and efficiency
      also decreased in the fear word dual task, relative to the neutral word memory
      dual task. Subjective measures of performance indicated that climbers were aware
      of impaired climbing performance in the dual tasks, relative to the climbing-only
      condition, but that they were not aware of the increased impairment caused by the
      fear words. These findings have important theoretical and practical implications,
      particularly in occupational settings requiring climbing-like operations, such as
      fire-fighting and search and rescue. 

PMID- 23873436
TI  - Salvia miltiorrhiza induces VEGF expression and regulates expression of VEGF
      receptors in osteoblastic cells.
AB  - This study investigated in vitro whether Salvia Miltiorrhiza Bunge (SM) induces
      vascular endothelial growth factor (VEGF) expression and regulates expression of
      VEGF receptors 1 (VEGFR-1) and 2 (VEGFR-2) on osteoblasts. MC3T3-E1 cells were
      cultured with SM and VEGF at points 24, 48 and 72 h. A blank control was
      included. The mRNA expression of VEGF, VEGFR-1 and VEGFR-2 was examined using
      real-time polymerase chain reaction. VEGF protein expression was examined using
      enzyme linked immunosorbent assay. SM increased VEGF mRNA expression by 21% at 24
      h (p < 0.05), 5% (p < 0.05) at 48 h and 74% (p < 0.001) at 72 h, while external
      VEGF intervention decreased the internal VEGF expression by 51% at 24 h (p <
      0.001) and increased it by 126% at 72 h (p < 0.001). SM increased VEGF protein at
      72 h (p < 0.05). VEGFR-1 mRNA expression, in response to SM, decreased by 8% (p <
      0.05) at 72 h and decreased following VEGF at 24 and 72 h by 20% (p < 0.001) and
      15%, respectively, (p < 0.001). VEGFR-2 mRNA expression increased following SM at
      24 and 48 h by 25% (p < 0.05) and 73% (p < 0.05), respectively, and decreased at
      72 h by 13% (p < 0.05). It was concluded that SM modulated expression of VEGF and
      its receptors in MC3T3-E1 cells.

PMID- 23873437
TI  - Time-varying effect moderation using the structural nested mean model: estimation
      using inverse-weighted regression with residuals.
AB  - This article considers the problem of examining time-varying causal effect
      moderation using observational, longitudinal data in which treatment, candidate
      moderators, and possible confounders are time varying. The structural nested mean
      model (SNMM) is used to specify the moderated time-varying causal effects of
      interest in a conditional mean model for a continuous response given time-varying
      treatments and moderators. We present an easy-to-use estimator of the SNMM that
      combines an existing regression-with-residuals (RR) approach with an inverse
      probability-of-treatment weighting (IPTW) strategy. The RR approach has been
      shown to identify the moderated time-varying causal effects if the time-varying
      moderators are also the sole time-varying confounders. The proposed IPTW+RR
      approach provides estimators of the moderated time-varying causal effects in the
      SNMM in the presence of an additional, auxiliary set of known and measured time
      varying confounders. We use a small simulation experiment to compare IPTW+RR
      versus the traditional regression approach and to compare small and large sample
      properties of asymptotic versus bootstrap estimators of the standard errors for
      the IPTW+RR approach. This article clarifies the distinction between time-varying
      moderators and time-varying confounders. We illustrate the methodology in a case
      study to assess if time-varying substance use moderates treatment effects on
      future substance use.

PMID- 23873438
TI  - Vitamin B12, folic acid, and bone.
AB  - Vitamin B12 and folic acid deficiency are associated with a higher serum
      concentration of homocysteine. A high serum homocysteine is a risk factor for
      fractures. Both vitamins play a role in the remethylation of homocysteine to
      methionine. The pathophysiology from a high serum homocysteine to fractures is
      not completely clear, but might involve bone mineral density, bone turnover, bone
      blood flow, DNA methylation, and/or physical function and fall risk. Genetic
      variation, especially polymorphisms of the gene encoding for
      methylenetetrahydrofolate reductase may play a role in homocysteine metabolism
      and fracture risk. It is uncertain whether supplementation with vitamin B12 and
      folate can decrease fracture incidence. One double blind clinical trial in post
      stroke patients showed that these B vitamins could decrease hip fracture
      incidence, but the results of further clinical trials should be awaited before a
      definite conclusion can be drawn.

PMID- 23873440
TI  - Revisiting the Rorschach ink-blots: from iconography and psychology to
      neuroscience.

PMID- 23873441
TI  - The time-evolution of DCIS size distributions with applications to breast cancer
      growth and progression.
AB  - Ductal carcinoma in situ (DCIS) lesions are non-invasive tumours of the breast
      that are thought to precede most invasive breast cancers (IBCs). As individual
      DCIS lesions are initiated, grow and invade (i.e. become IBC), the size
      distribution of the DCIS lesions present in a given human population will evolve.
      We derive a differential equation governing this evolution and show, for given
      assumptions about growth and invasion, that there is a unique distribution which
      does not vary with time. Further, we show that any initial distribution converges
      to this stationary distribution exponentially quickly. Therefore, it is
      reasonable to assume that the stationary distribution governs the size of DCIS
      lesions in human populations which are relatively stable with respect to the
      determinants of breast cancer. Based on this assumption and the size data of 110
      DCIS lesions detected in a mammographic screening programme between 1993 and
      2000, we produce maximum likelihood estimates for certain growth and invasion
      parameters. Assuming that DCIS size is proportional to a positive power p of the
      time since tumour initiation, we estimate p to be 0.50 with a 95% confidence
      interval of (0.35, 0.71). Therefore, we estimate that DCIS lesions follow a
      square-root growth law and hence that they grow rapidly when small and relatively
      slowly when large. Our approach and results should be useful for other
      mathematical studies of cancer, especially those investigating biological
      mechanisms of invasion. 

PMID- 23873442
TI  - Improved hidden Markov model for nosocomial infections.
AB  - We propose a novel hidden Markov model (HMM) for parameter estimation in hospital
      transmission models, and show that commonly made simplifying assumptions can lead
      to severe model misspecification and poor parameter estimates. A standard HMM
      that embodies two commonly made simplifying assumptions, namely a fixed patient
      count and binomially distributed detections is compared with a new alternative
      HMM that does not require these simplifying assumptions. Using simulated data, we
      demonstrate how each of the simplifying assumptions used by the standard model
      leads to model misspecification, whereas the alternative model results in
      accurate parameter estimates. 

PMID- 23873443
TI  - A rare case of interparietal incisional hernia from 8 mm trocar site after robot
      assisted laparoscopic prostatectomy.
AB  - Trocar site hernia arising from 8 mm robotic port is very rare despite the
      increasing prevalence of robot-assisted surgeries. To date, there had been only a
      single case reported in the literature. We report a case of small bowel
      obstruction secondary to an interparietal trocar site incisional hernia after
      robot-assisted laparoscopic prostatectomy. Meticulous closure of 8 mm robotic
      trocar sites associated with large peritoneal defect at the end of surgery should
      be performed. 

PMID- 23873444
TI  - Versatile Reactivity of Scorpionate-Anchored Yttrium-Dialkyl Complexes towards
      Unsaturated Substrates.
AB  - A series of unusual chemical-bond transformations were observed in the reactions
      of high active yttrium-dialkyl complexes with unsaturated small molecules. The
      reaction of scorpionate-anchored yttrium-dibenzyl complex [Tp(Me2)Y(CH2Ph)2(thf)]
      (1, Tp(Me2)=tri(3,5-dimethylpyrazolyl)borate) with phenyl isothiocyanate led to
      C=S bond cleavage to give a cubane-type yttrium-sulfur cluster, {Tp(Me2)Y(MU3
      S)}4 (2), accompanied by the elimination of PhN-C(CH2Ph)2. However, compound 1
      reacted with phenyl isocyanate to afford a C(sp(3)) H activation product,
      [Tp(Me2)Y(thf){MU-eta(1):eta(3)-OC(CHPh)NPh}{MU-eta(3):eta(2)
      OC(CHPh)NPh}YTp(Me2)] (3). Moreover, compound 1 reacted with phenylacetonitrile
      at room temperature to produce gamma-deprotonation product
      [(Tp(Me2))2Y](+)[Tp(Me2)Y(N=C=CHPh)3](-) (6), in which the newly formed N=C=CHPh
      ligands bound to the metal through the terminal nitrogen atoms. When this
      reaction was carried out in toluene at 120  degrees C, it gave a tandem gamma
      deprotonation/insertion/partial-Tp(Me2)-degradation product, [(Tp(Me2)Y)2(MU
      Pz)2{MU-eta(1):eta(3)-NC(CH2Ph)CHPh}] (7, Pz=3,5-dimethylpyrazolyl).

PMID- 23873439
TI  - The nuclear envelope LEM-domain protein emerin.
AB  - Emerin, a conserved LEM-domain protein, is among the few nuclear membrane
      proteins for which extensive basic knowledge--biochemistry, partners, functions,
      localizations, posttranslational regulation, roles in development and links to
      human disease--is available. This review summarizes emerin and its emerging roles
      in nuclear "lamina" structure, chromatin tethering, gene regulation, mitosis,
      nuclear assembly, development, signaling and mechano-transduction. We also
      highlight many open questions, exploration of which will be critical to
      understand how this intriguing nuclear membrane protein and its "family"
      influence the genome.

PMID- 23873445
TI  - Supramolecular organic-inorganic hybrid assemblies with tunable particle size:
      interplay of three noncovalent interactions.

PMID- 23873446
TI  - Desorption electrospray ionization mass spectrometry (DESI-MS) applied to the
      speciation of arsenic compounds from fern leaves.
AB  - The different chemical forms of arsenic compounds, including inorganic and
      organic species, present distinct environmental impacts and toxicities.
      Desorption electrospray ionization mass spectrometry (DESI-MS) is an excellent
      technique for in situ analysis, as it operates under atmospheric pressure and
      room temperature and is conducted with no/minimal sample pretreatment. Aimed at
      expanding its scope, DESI-MS is applied herein for the quick and reliable
      detection of inorganic (arsenate--As(V): AsO4(3-) and arsenite--As(III): AsO2(-))
      and organic (dimethylarsinic acid--DMA: (CH3)2AsO(OH) and disodium methyl
      arsonate hexahydrate: CH3AsO3.2Na.6H2O) arsenic compounds in fern leaves.
      Operational conditions of DESI-MS were optimized with DMA standard deposited on
      paper surfaces to improve ionization efficiency and detection limits. Mass
      spectra data for all arsenic species were acquired in both the positive and
      negative ion modes. The positive ion mode was shown to be useful in detecting
      both the organic and inorganic arsenic compounds. The negative ion mode was shown
      only to be useful in detecting As(V) species. Moreover, MS/MS spectra were
      recorded to confirm the identity of each arsenic compound by the characteristic
      fragmentation profiles. Optimized conditions of DESI-MS were applied to the
      analysis of fern leaves. LC-ICP-MS was employed to confirm the results obtained
      by DESI-MS and to quantify the arsenic species in fern leaves. The results
      confirmed the applicability of DESI-MS in detecting arsenic compounds in complex
      matrices.

PMID- 23873447
TI  - C-H functionalization: thoroughly tuning ligands at a metal ion, a chemist can
      greatly enhance catalyst's activity and selectivity.
AB  - This brief essay consists of a few "exciting stories" devoted to relations within
      a metal-complex catalyst between a metal ion and a coordinated ligand. When, as
      in the case of a human couple, the rapport of the partners is cordial and a love
      cements these relations, a chemist finds an ideal married couple, in other words
      he obtains a catalyst of choice which allows him to functionalize C-H bonds very
      efficiently and selectively. Examples of such lucky marriages in the catalytic
      world of ions and ligands are discussed here. Activity of the catalyst is
      characterized by turnover number (TON) or turnover frequency (TOF) as well as by
      yield of a target product. Introducing a chelating N,N- or N,O-ligand to the
      catalyst molecule (this can be an iron or manganese derivative) sharply enhances
      its activity. However, the activity of vanadium derivatives (with additionally
      added to the solution pyrazinecarboxylic acid, PCA) as well as of various osmium
      complexes does not dramatically depend on the nature of ligands surrounding metal
      ions. Complexes of these metals are very efficient catalysts in oxidations with
      H2O2. Osmium derivatives are record-holders exhibiting extremely high TONs
      whereas vanadium complexes are on the second position. Finally, elegant examples
      of alkane functionalization on the ions of non-transition metals (aluminium,
      gallium etc.) are described when one ligand within the metal complex (namely,
      hydroperoxyl ligand HOO(-)) helps other ligand of this complex (H2O2 molecule
      coordinated to the metal) to disintegrate into two species, generating very
      reactive hydroxyl radical. Hydrogen peroxide molecule, even ligated to the metal
      ion, is perfectly stable without the assistance of the neighboring HOO(-) ligand.
      This ligand can be easily oxidized donating an electron to its partner ligand
      (H2O2). In an analogous case, when the central ion in the catalyst is a
      transition metal, this ion changing its oxidation state can donate an electron to
      the coordinated H2O2 fragment. This provokes the O-O bond rupture in the hydrogen
      peroxide molecule as is assumed for the role of Fe(2+) ions in the Fenton system.

PMID- 23873448
TI  - Remarkable magnetism and ferromagnetic coupling in semi-sulfuretted transition
      metal dichalcogenides.
AB  - Motivated by recent investigations of semi-decorated two dimensional honeycomb
      structures, we demonstrated, via spin-polarized molecular-dynamics simulations
      and density-functional-theory calculations, that semi-sulfuretted transition
      metal dichalcogenides of MX type (M = V, Nb, Ta; X = S, Se, Te) are stable and
      display remarkable magnetism. The unpaired d electron of the transition-metal
      atom arising from the breakage of the M-X bond is the mechanism behind the
      induction of the magnetism. The remarkable magnetism of the transition-metal
      atoms is caused by ferromagnetic coupling due to the competitive effects of
      through-bond interactions and through-space interactions. This implies the
      existence of an infinite ferromagnetic sheet with structural integrity and
      magnetic homogeneity. The estimated Curie temperatures suggest that the
      ferromagnetism can be achieved above room temperature in the VS, VSe, VTe, NbTe
      and TaTe sheets. Depending on the species of the M and X atoms, the MX sheet can
      be a magnetic metal, magnetic semiconductor or half-metal. Furthermore, in
      contrary to the recently reported semi-hydrogenated and semi-fluorinated layered
      materials consisting of B, C, N, etc., the MX sheets with many unpaired d
      electrons can offer a much stronger spin polarization and possess a more stable
      ferromagnetic coupling, which is critical for practical nanoscale device
      applications. 

PMID- 23873449
TI  - Permeability enhancement for transdermal delivery of large molecule using low
      frequency sonophoresis combined with microneedles.
AB  - Transdermal drug delivery is limited by the high resistance of skin towards
      diffusion of high-molecular-weight drugs. This is mainly because of the fact that
      the outer layer of the skin, that is the stratum corneum, can prevent diffusion
      of molecules whose molecular weight is greater than 500 Da. Sonophoresis can be
      used to enhance the permeability of the skin. However, in the delivery of large
      molecules, ultrasound alone cannot provide sufficient permeability enhancement.
      In addressing this issue, we propose optimised ultrasound combined with
      microneedles to further increase the permeation rates. In this paper, we use
      porcine ear skin to simulate human skin and treat the skin samples with both
      ultrasound and microneedles. Further, bovine serum albumin (BSA) is used as a
      model of larger molecular weight molecule. Our results show that the permeability
      of BSA is increased to 1 MUm/s with the combination of 1.5 mm microneedles patch
      and 15-W ultrasound output which is about 10 times higher than the permeability
      obtained in passive diffusion. Diffusion with only microneedles or ultrasound pre
      treatment is also tested. The maximum permeability from microneedles and
      ultrasound treatment reached 0.43 and 0.4 MUm/s, respectively.

PMID- 23873450
TI  - Horsemeat review highlights confusion about FSA's role.

PMID- 23873452
TI  - FAO and OIE ease moratorium on research on rinderpest virus.

PMID- 23873454
TI  - EFRACom criticised for proposal to limit ban on the use of wild animals in
      circuses.

PMID- 23873455
TI  - Chimps fitted with heart monitors.

PMID- 23873456
TI  - Website to help keep chickens covered.

PMID- 23873457
TI  - Collaborative project seeks new solutions to control Salmonella in cattle.

PMID- 23873458
TI  - Vet to be removed from the Register following multiple complaints.

PMID- 23873459
TI  - Chance to name a hound for a hero.

PMID- 23873460
TI  - Advice for pet owners on dealing with emergencies.

PMID- 23873461
TI  - Confirmation of SBV disease in suckler calves in Scotland.

PMID- 23873462
TI  - MRI and navicular disease--on the brink of success or another false dawn?

PMID- 23873463
TI  - Veterinary business management education: why, how, when and who?

PMID- 23873464
TI  - Diagnosing ovine pulmonary adenocarcinoma.

PMID- 23873465
TI  - Welsh TB initiative.

PMID- 23873466
TI  - Ragwort toxicity in cattle.

PMID- 23873467
TI  - Subsidised neutering by practices.

PMID- 23873468
TI  - Use of Pexion.

PMID- 23873469
TI  - List of vets willing to treat pet fish.

PMID- 23873470
TI  - 150 years of the Yorkshire Veterinary Society.

PMID- 23873471
TI  - R521C mutation in the FUS/TLS gene presenting as juvenile onset flail leg
      syndrome.

PMID- 23873472
TI  - Cardiorespiratory fitness, body mass index, and heart failure mortality in men:
      Cooper Center Longitudinal Study.
AB  - BACKGROUND: We evaluated the individual and joint associations among
      cardiorespiratory fitness (CRF), body mass index, and heart failure (HF)
      mortality, as well as the additive effect of an increasing number of
      cardiovascular risk factors on HF mortality in fit versus unfit men. METHODS AND
      RESULTS: A total of 44 674 men without a history of cardiovascular disease
      underwent a baseline examination between 1971 and 2010. Measures included body
      mass index and CRF quantified as duration of maximal treadmill exercise testing.
      Participants were divided into age-specific low, moderate, and high CRF
      categories. Hazard ratios were computed with Cox regression analysis. During a
      mean follow-up of 19.8+/-10.4 years, 153 HF deaths occurred. Adjusted hazard
      ratios across high, moderate, and low CRF categories were 1.0, 1.63, and 3.97,
      respectively, whereas those of normal, overweight, and obese body mass index
      categories were 1.0, 1.56, and 3.71, respectively (P for trend <0.0001 for each).
      When grouped into categories of fit and unfit (upper 80% and lower 20% of CRF
      distribution, respectively), hazard ratios were significantly lower in fit
      compared with unfit men in normal and overweight body mass index strata (P<0.002)
      but not in obese men. Within men matched for the same number of HF risk factors,
      fit men had significantly lower HF mortality than unfit men (P<=0.02).
      CONCLUSIONS: Higher baseline CRF is associated with lower HF mortality risk in
      men, regardless of the number of HF risk factors present. Men should be counseled
      on physical activity with the goal of achieving at least a moderate level of CRF,
      thereby presumably decreasing their risk of HF mortality.

PMID- 23873474
TI  - Cardiovascular magnetic resonance characteristics in children with hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Cardiovascular magnetic resonance has provided important information
      on the diagnosis and risk stratification of hypertrophic cardiomyopathy (HCM) in
      adults; however, comparable data are absent for HCM in children. The study was
      performed to evaluate cardiovascular magnetic resonance characteristics in
      children with idiopathic HCM. METHODS AND RESULTS: Cardiovascular magnetic
      resonance was performed in 71 consecutive children with idiopathic HCM (age,
      12.8+/-4.1 years; 46 boys and 25 girls). The left ventricular (LV) parameters
      indexed by body surface area were calculated and compared with those in 71
      healthy children (age, 13.1+/-3.3 years; 51 boys and 20 girls). Among those with
      HCM, concentric LV hypertrophy occurred in 9 patients (12.7%): in 2 children, it
      progressed into end-stage phase. The prevalence of late gadolinium enhancement
      (LGE) was 73%, and the extent of LGE was 10.4+/-8.3% of LV mass. Children with
      HCM with LGE had greater LV mass indexed (112.7+/-57.9 versus 70.3+/-37.4 g/m(2);
      P=0.025) but had no significant difference in maximal LV wall thickness indexed
      (19.4+/-6.3 versus 18.1+/-7.9 mm/m(2); P=0.513). In addition, the hazard ratio of
      adverse events for the extent of LGE was 1.1 (P=0.004). The follow-up (2.4+/-1.6
      years) demonstrated that LGE was associated with adverse events in children with
      HCM (log-rank; P=0.029). CONCLUSIONS: The prevalence and extent of LGE in
      children with HCM approximate to those in adults with HCM. Furthermore, children
      with HCM with LGE tend to have adverse events, and larger researches with longer
      follow-up are required.

PMID- 23873473
TI  - The COP9 signalosome is required for autophagy, proteasome-mediated proteolysis,
      and cardiomyocyte survival in adult mice.
AB  - BACKGROUND: The COP9 signalosome (CSN) is an evolutionarily conserved protein
      complex composed of 8 unique protein subunits (CSN1 through CSN8). We have
      recently discovered in perinatal mouse hearts that CSN regulates not only
      proteasome-mediated proteolysis but also macroautophagy. However, the
      physiological significance of CSN in a post-mitotic organ of adult vertebrates
      has not been determined. We sought to study the physiological role of CSN8/CSN in
      adult mouse hearts. METHODS AND RESULTS: Csn8 was conditionally ablated in the
      cardiomyocytes of adult mice (CSN8(CKO)) using a temporally controlled Cre-LoxP
      system. Loss of CSN8 accumulated the neddylated forms of cullins and noncullin
      proteins, increased ubiquitinated proteins, and stabilized a surrogate substrate
      of the proteasome in the heart. Autophagic flux was significantly decreased,
      whereas autophagosomes were markedly increased in CSN8(CKO) hearts, indicative of
      impaired autophagosome removal. Furthermore, we observed increased oxidized
      proteins, massive necrotic cardiomyocytes, and morphological and functional
      changes characteristic of dilated cardiomyopathy in CSN8(CKO) mice. CONCLUSIONS:
      CSN deneddylates substrates more than cullins and is indispensable to
      cardiomyocyte survival in not only perinatal hearts but also adult hearts.
      CSN8/CSN regulates both proteasome-mediated proteolysis and the autophagic
      lysosomal pathway, critical to the removal of oxidized proteins in the heart.

PMID- 23873475
TI  - Internalizing antecedents and consequences of binge-eating behaviors in a
      community-based, urban sample of African American females.
AB  - The etiology of problem-eating behaviors is often overlooked in research as it
      typically shares many symptoms with other more common psychiatric illnesses.
      Binge-eating problems are at the forefront of the popular media because of the
      connection to obesity; therefore, increased knowledge of binge eating problems,
      particularly the internalizing antecedents and consequences will have
      implications in a multitude of domains, including prevention programs aimed at
      physical and mental health. The current study examines the antecedents of binge
      eating behaviors by exploring how the growth of internalizing symptoms influences
      the proximal outcome of a binge-eating inventory in a longitudinal sample of
      African American girls. Additional consequences of binge-eating problems are also
      explored. This study focuses on binge-eating problems in order to present
      valuable information for prevention scientists who wish to develop target
      individuals at high risk for internalizing problems such as suicide.

PMID- 23873476
TI  - The osteogenic potential of the marine-derived multi-mineral formula aquamin is
      enhanced by the presence of vitamin D.
AB  - Bone degenerative diseases are on the increase globally and are often problematic
      to treat. This has led to a demand to identify supplements that aid bone growth
      and formation. Aquamin is a natural multi-mineral food supplement, derived from
      the red algae Lithothamnion species which contains calcium, magnesium and 72
      other trace minerals. It has been previously reported to increase bone formation
      and mineralisation. This study aimed to investigate the 28 day in vitro
      osteogenic response of Aquamin supplemented with Vitamin D. The osteogenic
      potential of MC3T3-E1 osteoblast-like cells was analysed in standard osteogenic
      medium supplemented with Aquamin +/- Vitamin D3, and the controls consisted of
      osteogenic medium, +/- Vitamin D3. Proliferation of osteoblasts, metabolic
      activity and cell viability did not differ between Aquamin and the osteogenic
      control groups. Alkaline phosphatase (ALP) levels and mineralisation were
      increased by the supplementation of Aquamin, and the addition of Vitamin D3
      increased mineralisation for all groups. The combination of Aquamin and Vitamin
      D3 yielded a significant increase in ALP and mineralisation over Aquamin alone
      and the standard osteogenic control +/- Vitamin D3. This study demonstrates that
      Aquamin aids osteogenesis, and that its osteogenic response can be enhanced by
      combining Aquamin with Vitamin D3.

PMID- 23873477
TI  - Confidence intervals after multiple imputation: combining profile likelihood
      information from logistic regressions.
AB  - In the logistic regression analysis of a small-sized, case-control study on
      Alzheimer's disease, some of the risk factors exhibited missing values,
      motivating the use of multiple imputation. Usually, Rubin's rules (RR) for
      combining point estimates and variances would then be used to estimate
      (symmetric) confidence intervals (CIs), on the assumption that the regression
      coefficients were distributed normally. Yet, rarely is this assumption tested,
      with or without transformation. In analyses of small, sparse, or nearly separated
      data sets, such symmetric CI may not be reliable. Thus, RR alternatives have been
      considered, for example, Bayesian sampling methods, but not yet those that
      combine profile likelihoods, particularly penalized profile likelihoods, which
      can remove first order biases and guarantee convergence of parameter estimation.
      To fill the gap, we consider the combination of penalized likelihood profiles
      (CLIP) by expressing them as posterior cumulative distribution functions (CDFs)
      obtained via a chi-squared approximation to the penalized likelihood ratio
      statistic. CDFs from multiple imputations can then easily be averaged into a
      combined CDF c , allowing confidence limits for a parameter beta  at level 1 -
      alpha to be identified as those beta* and beta** that satisfy CDF c (beta*) =
      alpha / 2 and CDF c (beta**) = 1 - alpha / 2. We demonstrate that the CLIP method
      outperforms RR in analyzing both simulated data and data from our motivating
      example. CLIP can also be useful as a confirmatory tool, should it show that the
      simpler RR are adequate for extended analysis. We also compare the performance of
      CLIP to Bayesian sampling methods using Markov chain Monte Carlo. CLIP is
      available in the R package logistf.

PMID- 23873478
TI  - The role of p53 in combination radioimmunotherapy with 64Cu-DOTA-cetuximab and
      cisplatin in a mouse model of colorectal cancer.
AB  - Radioimmunotherapy has been successfully used in the treatment of lymphoma but
      thus far has not demonstrated significant efficacy in humans beyond disease
      stabilization in solid tumors. Radioimmunotherapy with (64)Cu was highly
      effective in a hamster model of colorectal cancer, but targeted radiotherapies
      with this radionuclide have since not shown as much success. It is widely known
      that mutations in key proteins play a role in the success or failure of cancer
      therapies. For example, the KRAS mutation is predictive of poor response to anti
      epidermal growth factor receptor therapies in colorectal cancer, whereas p53 is
      frequently mutated in tumors, causing resistance to multiple therapeutic
      regimens. METHODS: We previously showed that nuclear localization of (64)Cu
      labeled DOTA-cetuximab was enhanced in p53 wild-type tumor cells. Here, we
      examine the role of p53 in the response to radioimmunotherapy with (64)Cu-DOTA
      cetuximab in KRAS-mutated HCT116 tumor-bearing mice, with and without cisplatin,
      which upregulates wild-type p53. RESULTS: Experiments with HCT116 cells that are
      p53 +/+ (p53 wild-type) and -/- (p53 null) grown in cell culture demonstrated
      that preincubation with cisplatin increased expression of p53 and subsequently
      enhanced localization of (64)Cu from (64)Cu-acetate and (64)Cu-DOTA-cetuximab to
      the tumor cell nuclei. Radioimmunotherapy studies in p53-positive HCT116 tumor
      bearing mice, receiving either radioimmunotherapy alone or in combination with
      cisplatin, showed significantly longer survival in mice receiving unlabeled
      cetuximab or cisplatin alone or in combination (all, P < 0.01). In contrast, the
      p53-negative tumor-bearing mice treated with radioimmunotherapy alone or combined
      with cisplatin showed no survival advantage, compared with control groups (all, P
      > 0.05). CONCLUSION: Together, these data suggest that (64)Cu specifically
      delivered to epidermal growth factor receptor-positive tumors by cetuximab can
      suppress tumor growth despite the KRAS status and present opportunities for
      personalized clinical treatment strategies in colorectal cancer.

PMID- 23873479
TI  - Appendage patterning in the primitively wingless hexapods Thermobia domestica
      (Zygentoma: Lepismatidae) and Folsomia candida (Collembola: Isotomidae).
AB  - Arthropod appendages are among the most diverse animal organs and have been
      adapted to a variety of functions. Due to this diversity, it can be difficult to
      recognize homologous parts in different appendage types and different species.
      Gene expression patterns of appendage development genes have been used to
      overcome this problem and to identify homologous limb portions across different
      species and their appendages. However, regarding the largest arthropod group, the
      hexapods, most of these studies focused on members of the winged insects
      (Pterygota), but primitively wingless groups like the springtails (Collembola) or
      silverfish and allies (Zygentoma) are underrepresented. We have studied the
      expression of a set of appendage patterning genes in the firebrat Thermobia
      domestica and the white springtail Folsomia candida. The expressions of Distal
      less (Dll) and dachshund (dac) are generally similar to the patterns reported for
      pterygote insects. Modifications of gene regulation, for example, the lack of Dll
      expression in the palp of F. candida mouthparts, however, point to changes in
      gene function that can make the use of single genes and specific expression
      domains problematic for homology inference. Such hypotheses should therefore not
      rely on a small number of genes and should ideally also include information about
      gene function. The expression patterns of homothorax (hth) and extradenticle
      (exd) in both species are similar to the patterns of crustaceans and pterygote
      insects, but differ from those in chelicerates and myriapods. The proximal
      specificity of hth thus appears to trace from a common hexapod ancestor and also
      provides a link to the regulation of this gene in crustaceans. 

PMID- 23873480
TI  - Quantity matching by an orangutan (Pongo abelii).
AB  - An adult male orangutan (Pongo abelii) was presented with a series of delayed
      matching-to-sample (DMTS) tasks in which he was to match images based on (a) the
      number of individual animals depicted in the photograph (from 1 to 4), (b) the
      number of abstract shapes presented in the stimulus (from 1 to 4), or (c) the
      number of dots presented in the stimulus (from 1 to 4, 4-7, or 7-10). The spatial
      arrangement of the dots and the background color of the stimuli varied, and the
      size of the dots was manipulated to control for overall ratio of foreground to
      background. The subject's performance was not affected by these perceptual
      features, but was affected by the absolute difference and ratio between number of
      elements in the comparison stimuli. However, the relationship between these
      variables and his performance was not always linear as predicted by the analog
      magnitude model. In addition, the subject showed a high degree of transfer to
      novel numerosities up to ten, indicating that orangutans are capable of
      estimating quantity for a greater number of items than can presumably be
      subtilized by humans. 

PMID- 23873482
TI  - Clinical hypotension with co-prescription of macrolide antibiotics and calcium
      channel blockers in haemodialysis patients: a retrospective chart review.
AB  - BACKGROUND: Macrolide antibiotics inhibit the cytochrome p450 enzyme system,
      which metabolizes calcium-channel blockers. This may result in a clinically
      significant interaction, causing hypotension in patients co-prescribed these two
      drugs. Since these drugs are frequently used in the haemodialysis population, we
      studied the effect of their co-prescription on actual blood pressure. METHODS: A
      retrospective chart review of all haemodialysis patients was conducted to
      identify patients co-prescribed a macrolide and a dihydropyridine calcium-channel
      blocker. Blood pressure measurements before and during the macrolide co
      prescription were abstracted and compared using a student's t test. RESULTS: We
      identified 154 haemodialysis patients concurrently prescribed a macrolide
      antibiotic and a dihydropyridine calcium-channel blocker. There was no
      significant difference in episodes of intra-dialytic hypotension or actual blood
      pressure measurements in the period before macrolide co-prescription and the
      period during macrolide co-prescription. CONCLUSION: In contrast to hospitalized
      patients receiving dihydropyridine calcium-channel blockers, concurrent
      administration of a macrolide antibiotic for infection did not result in
      hypotension in haemodialysis outpatients. Further research should be undertaken
      before a change in clinical practice against their co-prescription is considered.

PMID- 23873483
TI  - The contrasting roles of lamin B1 in cellular aging and human disease.
AB  - The nuclear lamina underlies the inner nuclear membrane and consists of a
      proteinaceous meshwork of intermediate filaments: the A- and B-type lamins.
      Mutations in LMNA (encoding lamin A and C) give rise to a variety of human
      diseases including muscular dystrophies, cardiomyopathies and the premature aging
      syndrome progeria (HGPS). Duplication of the LMNB1 locus, leading to elevated
      levels of lamin B1, causes adult-onset autosomal dominant leukodystrophy (ADLD),
      a rare genetic disease that leads to demyelination in the central nervous system
      (CNS). Conversely, reduced levels of lamin B1 have been observed in HGPS patient
      derived fibroblasts, as well as fibroblasts and keratinocytes undergoing
      replicative senescence, suggesting that the regulation of lamin B1 is important
      for cellular physiology and disease. However, the causal relationship between low
      levels of lamin B1 and cellular senescence and its relevance in vivo remain
      unclear. How do elevated levels of lamin B1 cause disease and why is the CNS
      particularly susceptible to lamin B1 fluctuations? Here we summarize recent
      findings as to how perturbations of lamin B1 affect cellular physiology and
      discuss the implications this has on senescence, HGPS and ADLD. 

PMID- 23873484
TI  - Case report: Remote monitoring using Spectrum Medical Live Vue allows improved
      response time and improved quality of care for patients on cardiopulmonary
      support.
AB  - Clinician rounding on bedside extracorporeal membrane oxygenation (ECMO) is a
      common coverage practice at many centers across the USA. Occasionally, clinical
      issues or concerns may go unnoticed for a considerable period of time during the
      intervals of clinician rounds. We report a case utilizing the LiveVue (Spectrum
      Medical, Fort Mill, SC) remote monitoring for care of a patient on ECMO. A
      patient was placed on veno-arterial (VA) ECMO in our intensive care unit, using a
      Rotaflow centrifugal pump and a Quadrox D polymethylpentene (PMP) fiber
      oxygenator (both Maquet, Fairfield, NJ). Following ECMO initiation and
      stabilization, a two-hour rounding schedule was established for the covering
      perfusionist. On day two, shortly after the perfusionist had rounded, the ECMO
      flow began fluctuating between 0.1 and 2.1 L/min. A compliance alert (i.e. red
      flashing notification) was recognized by the perfusion team on a large screen
      monitor installed in the perfusion pump room. Immediate response from the
      perfusion team identified venous inflow obstruction due to cannula malposition.
      The pump revolutions per minute (rpm) and, thus, the resulting flow were
      temporarily reduced to prevent vessel intimal damage and the surgical team was
      summoned to reposition the venous cannula. Later in that ECMO run, a steady rise
      in pre-oxygenator pressure was noted by the perfusionist. This increasingly
      concerning event was able to be trended and monitored with the LiveVue from a
      remote location. After a few hours, a compliance alert was noticed again on the
      LiveVue screen in the pump room. The pre-oxygenator pressure increased by 150
      mmHg and the circuit flow decreased by half. Again, the perfusionist response was
      immediate and an oxygenator change-out ensued. Once more, a potentially dangerous
      clinical scenario was avoided with continuous critical parameter remote
      monitoring using the LiveVue system. 

PMID- 23873485
TI  - Commentary on: Case report: Remote monitoring using Spectrum Medical, Live Vue
      allows improved response time and improved quality of care for patients on
      cardiopulmonary support.

PMID- 23873486
TI  - Commentary on: Managing the extracorporeal membrane oxygenation (ECMO) circuit
      integrity and safety utilizing the perfusionist as the "ECMO Specialist".

PMID- 23873487
TI  - Managing the extracorporeal membrane oxygenation (ECMO) circuit integrity and
      safety utilizing the perfusionist as the "ECMO Specialist".
AB  - Extracorporeal membrane oxygenation (ECMO) is an extracorporeal technique of
      providing both cardiac and respiratory support to patients whose heart and lungs
      are so severely diseased or damaged that they can no longer serve their function.
      Neonatal and pediatric ECMO was accepted as practice in the early 1990s and
      according to the Extracorporeal Life Support Organization, ELSO; of the >50,000
      patients registered, 73% have survived extracorporeal life support (ECLS). It is
      not uncommon to find initial cannulation of a patient receiving ECMO performed by
      a surgeon and then the maintenance of the patient being left in the hands of
      various others deemed as the "ECMO Specialists". The specialist has a broad base
      of professionals, including: nurses, respiratory therapists, perfusionists and
      physicians. Each institution, having its own unique training for these
      individuals, has provided a milieu for education, but does not share an
      established standard of care. From 2009, after the surge of the H1N1 epidemic,
      adult ECMO has been increasing; n=53 in 2010 to n=110 in 2012 at our institution.
      The perfusionist has been the "specialist" for ECMO at our institution since the
      early 1990s and remained at bedside during ECMO. We have now developed a safe
      circuit and fiscally responsible staffing model that utilizes a perfusionist and
      a telemetry-based electronic record keeper, permitting the perfusionist to leave
      the bedside and interact with the circuit when necessary. This has permitted an
      expansive growth of ECMO in our intensive care units at our facility
      incorporating a multidisciplinary collaboration system wide. 

PMID- 23873488
TI  - Reliability of automatic biometric iris recognition after phacoemulsification or
      drug-induced pupil dilation.
AB  - PURPOSE: To investigate the reliability of a biometric iris recognition system
      for personal authentication after cataract surgery or iatrogenic pupil dilation.
      METHODS: This was a prospective, nonrandomized, single-center, cohort study for
      evaluating the performance of an iris recognition system 2-24 hours after
      phacoemulsification and intraocular lens implantation (group 1) and before and
      after iatrogenic pupil dilation (group 2). RESULTS: Of the 173 eyes that could be
      enrolled before cataract surgery, 164 (94.8%) were easily recognized
      postoperatively, whereas in 9 (5.2%) this was not possible. However, these 9 eyes
      could be reenrolled and afterwards recognized successfully. In group 2, of a
      total of 184 eyes that were enrolled in miosis, a total of 22 (11.9%) could not
      be recognized in mydriasis and therefore needed reenrollment. No single case of
      false-positive acceptance occurred in either group. CONCLUSIONS: The results of
      this trial indicate that standard cataract surgery seems not to be a limiting
      factor for iris recognition in the large majority of cases. Some patients (5.2%
      in this study) might need "reenrollment" after cataract surgery. Iris recognition
      was primarily successful in eyes with medically dilated pupils in nearly 9 out of
      10 eyes. No single case of false-positive acceptance occurred in either group in
      this trial. It seems therefore that iris recognition is a valid biometric method
      in the majority of cases after cataract surgery or after pupil dilation.

PMID- 23873489
TI  - Red-free light for measurement of intraocular pressure using Goldmann applanation
      tonometer without fluorescein.
AB  - PURPOSE: To evaluate the use of red-free light for the measurement of intraocular
      pressure (IOP) using a Goldmann applanation tonometer without fluorescein.
      METHODS: This cross-sectional study was carried out on 500 eyes in 250 patients
      attending the Ophthalmology Outpatient Clinic at Suez Canal University Hospital.
      The IOP was measured using a Goldmann applanation tonometer mounted on a Haag
      Streit slit-lamp. The measurements were performed first using red-free light
      without fluorescein. Then the measurements were repeated with cobalt blue light
      and topical fluorescein on the same eyes. RESULTS: The mean IOP was 15.23 +/- 3.3
      (SD) mm Hg using the red-free light without fluorescein, whereas it was 15.78 +/-
      3.7 (SD) mm Hg when measured using cobalt blue light after the application of
      fluorescein to the conjunctival sac. This difference was not statistically
      significant. CONCLUSION: Measurement of IOP with a Goldmann applanationtonometer
      with red-free light and without the use of fluorescein is simple, saves time, and
      gives an accurate IOP measurement relative to the traditional measurement
      technique with cobalt blue light and topical fluorescein.

PMID- 23873481
TI  - Allopurinol hypersensitivity: a systematic review of all published cases, 1950
      2012.
AB  - BACKGROUND: Allopurinol is the primary therapy for the management of chronic
      gout. Utilization of allopurinol has increased in tandem with the growing
      prevalence of gout globally. This exposes more patients to the risk of
      allopurinol hypersensitivity (AH), a rare adverse reaction characterised by a
      spectrum of cutaneous reactions and systemic manifestations. Severe forms of AH
      have been associated with high mortality. The pathophysiology underlying this
      reaction remains unknown, but several risk factors have been proposed. OBJECTIVE:
      The aim of this study was to review all published cases of AH documented in the
      literature in order to better understand the constellation of factors
      predisposing to this reaction, building on previous reviews by Lupton and Odom,
      Singer and Wallace and Arellano and Sacristan. METHODS: A literature search was
      conducted in MEDLINE and EMBASE to identify relevant articles published between
      January 1950 and December 2012, with no language restrictions imposed. Articles
      that were included reported either allopurinol-induced cutaneous manifestations
      alone or satisfied the diagnostic criteria for AH as defined by Singer and
      Wallace. RESULTS: Nine hundred and one patients (overall AH cohort) were
      identified from 320 publications. Of these patients, 802 satisfied the Singer and
      Wallace criteria ('Singer and Wallace' cohort) while 99 patients had only mild
      cutaneous manifestations ('non-Singer and Wallace' cohort). Data were often
      incomplete; hence the results reported reflect the fractions of the subsets of
      the cohort where the data in question were available. In the overall AH cohort,
      58 % (416/722) were male. The majority (73 %; 430/590) of patients were Asian.
      Renal impairment (48 %; 182/376) and hypertension (42 %; 160/376) were the most
      common chronic conditions; accordingly, diuretics (45 %; 114/252) and
      antihypertensives (39 %; 99/252) were the most prevalent concomitant medications.
      Allopurinol was prescribed for approved indications (chronic gout and
      chemoprophylaxis) in only 40 % (186/464) of patients. The median allopurinol dose
      was 300 mg/day (range 10-1,000 mg/day) and was taken by 50 % (168/338). There was
      no significant association between a higher dose (>300 mg/day) and an increased
      risk of severe cutaneous manifestations [odds ratio (OR) 1.76; 95 % CI 0.73-4.22;
      p = 0.23]. Approximately 90 % (489/538) of patients developed AH within 60 days
      of initiating allopurinol therapy. Serum oxypurinol (the active metabolite of
      allopurinol) concentration was only recorded in six patients, four of whom had
      levels within the putative therapeutic range of 30-100 MUmol/L. The HLA-B*5801
      allele was present in 99 % (166/167) of patients tested, with the majority
      (147/166) being of Asian ancestry. The all-cause mortality rate was 14 %
      (109/788) with 94 AH-related deaths, all of which occurred in the cohort meeting
      the Singer and Wallace criteria. LIMITATIONS: The publications included in this
      review utilized different laboratory reference ranges to classify the non
      cutaneous manifestations of AH; this may have introduced some variation in the
      cases identified as AH. A majority of the articles included in this analysis
      consisted of case reports and series--publication types that are not recognized
      as best-quality evidence; this thus limited the conclusions we could draw about
      the many risk factors we were interested in evaluating. CONCLUSIONS: Risk factors
      associated with AH, such as concomitant diuretic use, pre-existing renal
      impairment and recent initiation of allopurinol, were commonly present in AH
      patients; however, their role in the mechanism of AH remains to be established. A
      clear risk factor was the HLA-B*5801 status; this was especially relevant in
      Asian populations where there is a higher carriage rate of the allele. High
      allopurinol dose, previously suggested to be a risk factor, was not confirmed as
      such. The paucity of well-documented case reports and studies of AH render it
      difficult to draw more concrete conclusions or construct a meticulous profile of
      patients at risk of AH. Future case reports of AH need to be better documented to
      contribute to understanding the risks for, and mechanisms of, AH.

PMID- 23873490
TI  - Phacoemulsification with Malyugin ring in an eye ?with iridoschisis, narrow
      pupil, anterior and posterior synechiae: case report.
AB  - PURPOSE: Iridoschisis is a rare, bilateral condition, found in the elderly and
      connected with the coexistence of closed-angle glaucoma. Stromal atrophy or
      separation of the anterior from the posterior laminae with coexisting posterior
      synechiae are present. Phacoemulsification in eyes with a narrow pupil,
      unresponsive to preoperative pharmacologic mydriasis, is challenging.? METHODS:
      In the presented case of iridoschisis with anterior and posterior synechiae, 2
      ophthalmic viscosurgical devices were used and balanced salt solution was used as
      the infusion fluid. The Malyugin ring was used to widen and stabilize the pupil,
      synechiae were removed, and burst mode of phacoemulsification and "divide and
      conquer" technique of dividing the nucleus were used.? RESULTS: We present a case
      of iridoschisis with anterior and posterior synechiae, which was successfully
      operated for cataract using standard phacoemulsification with Malyugin ring. ?
      CONCLUSIONS: The case suggests that Malyugin ring is an effective intraoperative
      tool, which may assist the surgeon in cases of cataract with iridoschisis and
      both anterior and posterior synechiae.

PMID- 23873491
TI  - Ocular demodicidosis as a risk factor of adult recurrent chalazion.
AB  - PURPOSE: To report Demodex infestation in adult recurrent chalazion and its
      clinical response to weekly lid scrub with 50% tea tree oil (TTO) and daily lid
      scrub with tea tree shampoo. METHODS: This is a retrospective review of 30 adult
      patients (48 eyes) who presented with recurrent chalazion within 6 months after
      conventional treatment. Demodex was detected by random lash sampling and
      microscopic examination. Patients with confirmed ocular Demodex infestation were
      treated with weekly lid scrub with 50% TTO and daily lid scrub with tea tree
      shampoo. The study is limited by the lack of a control group. RESULTS: The mean
      age of patients was 39.1 +/- 10.2 years (range 18-69). The mean follow-up of
      patients is 10.0 +/- 3.0 months (range 6-24 months). Among 48 eyes with recurrent
      chalazion, Demodex mites were found in 35 (72.9%). Recurrent chalazion was found
      to be associated with ocular demodicidosis (Fisher exact test, p = 0.017). Tea
      tree oil treatment was given to 31 eyes with recurrent chalazion associated with
      Demodex infestation. Among the treatment group, all cases except one had no
      recurrence after the TTO treatment. The success rate of preventing recurrence is
      96.8%. Treatment of TTO was found to be associated with preventing recurrence of
      chalazion associated with Demodex infestation (Fisher exact test, p = 0.002).
      CONCLUSIONS: The possibility of demodicidosis should be considered in adults
      presenting with recurrent chalazia. Tea tree oil eyelid scrubs is an effective
      treatment in preventing recurrence.

PMID- 23873492
TI  - Riboflavin/UVA photochemical therapy for severe infectious keratitis.
AB  - PURPOSE: To describe the antibacterial activity of treatment with riboflavin and
      ultraviolet A light (UVA) in cases of severe infectious keratitis. METHODS: A
      retrospective analysis was performed of an interventional case series in which 6
      eyes of 6 patients with severe infectious keratitis, all of whom were refractive
      to multidrug conventional therapy, were treated with riboflavin/UVA. The
      procedure was conducted according to the standardized protocol of corneal
      collagen crosslinking (CXL) for keratoconus. Best spectacle-corrected visual
      acuity and clinical outcomes were evaluated before and during the follow-up
      period. RESULTS: Five of the 6 patients showed rapid reduction in symptoms and
      decreased infiltrate size after riboflavin/UVA photochemical therapy. Signs of
      infection and inflammation mostly resolved within 1 to 2 weeks after the
      treatment. Despite this therapy, one patient continued to deteriorate, and
      penetrating keratoplasty was performed. CONCLUSIONS: The adjunctive use of
      riboflavin/UVA photochemical therapy has a positive effect on refractory
      infectious keratitis. The treatment seems to be safe and effective and should be
      considered as part of the first-line therapy in severe cases of infectious
      keratitis.

PMID- 23873493
TI  - Listening to your heart and feeling yourself: effects of exposure to
      interoceptive signals during the ultimatum game.
AB  - The ultimatum game (UG) is commonly used to study the tension between financial
      self-interest and social equity motives. Here, we investigated whether
      experimental exposure to interoceptive signals influences participants' behavior
      in the UG. Participants were presented with various bodily sounds--i.e., their
      own heart, another person's heart, or the sound of footsteps--while acting both
      in the role of responder and proposer. We found that listening to one's own heart
      sound, compared to the other bodily sounds: (1) increased subjective feelings of
      unfairness, but not rejection behavior, in response to unfair offers and (2)
      increased the unfair offers while playing in the proposer role. These findings
      suggest that heightened feedback of one's own visceral processes may increase a
      self-centered perspective and drive socioeconomic exchanges accordingly. In
      addition, this study introduces a valuable procedure to manipulate online the
      access to interoceptive signals and for exploring the interplay between viscero
      sensory information and cognition.

PMID- 23873494
TI  - A model of motor performance during surface penetration: from physics to
      voluntary control.
AB  - The act of puncturing a surface with a hand-held tool is a ubiquitous but complex
      motor behavior that requires precise force control to avoid potentially severe
      consequences. We present a detailed model of puncture over a time course of
      approximately 1,000 ms, which is fit to kinematic data from individual punctures,
      obtained via a simulation with high-fidelity force feedback. The model describes
      puncture as proceeding from purely physically determined interactions between the
      surface and tool, through decline of force due to biomechanical viscosity, to
      cortically mediated voluntary control. When fit to the data, it yields parameters
      for the inertial mass of the tool/person coupling, time characteristic of force
      decline, onset of active braking, stopping time and distance, and late
      oscillatory behavior, all of which the analysis relates to physical variables
      manipulated in the simulation. While the present data characterize distinct
      phases of motor performance in a group of healthy young adults, the approach
      could potentially be extended to quantify the performance of individuals from
      other populations, e.g., with sensory-motor impairments. Applications to surgical
      force control devices are also considered.

PMID- 23873496
TI  - Using the concept of transient complex for affinity predictions in CAPRI rounds
      20-27 and beyond.
AB  - Predictions of protein-protein binders and binding affinities have traditionally
      focused on features pertaining to the native complexes. In developing a
      computational method for predicting protein-protein association rate constants,
      we introduced the concept of transient complex after mapping the interaction
      energy surface. The transient complex is located at the outer boundary of the
      bound-state energy well, having near-native separation and relative orientation
      between the subunits but not yet formed most of the short-range native
      interactions. We found that the width of the binding funnel and the electrostatic
      interaction energy of the transient complex are among the features predictive of
      binders and binding affinities. These ideas were very promising for the five
      affinity-related targets (T43-45, 55, and 56) of CAPRI rounds 20-27. For T43, we
      ranked the single crystallographic complex as number 1 and were one of only two
      groups that clearly identified that complex as a true binder; for T44, we ranked
      the only design with measurable binding affinity as number 4. For the nine
      docking targets, continuing on our success in previous CAPRI rounds, we produced
      10 medium-quality models for T47 and acceptable models for T48 and T49. We
      conclude that the interaction energy landscape and the transient complex in
      particular will complement existing features in leading to better prediction of
      binding affinities.

PMID- 23873497
TI  - How long do smoke alarms function? A cross-sectional follow-up survey of a smoke
      alarm installation programme.
AB  - OBJECTIVE: To assess the functionality of lithium-powered smoke alarms that had
      been installed through a community-based programme called Operation Installation
      (OI). METHODS: A random sample was chosen of homes that had received smoke alarms
      through OI, 2, 4, 6, 8 and 10 years previously. Sampled homes were visited, and
      information collected included functional status of smoke alarms. For homes in
      the 6-, 8- and 10-year sample, smoke alarms were removed and tested for battery
      and alarm function. RESULTS: 800 homes were included in the survey results; 1884
      smoke alarms had been installed through OI. The proportion of homes that had at
      least one functioning OI smoke alarm ranged from 91.8% for year 2 sample to 19.8%
      for year 10. Of the originally installed smoke alarms in year 10 sample, 45.5%
      had been removed and 59% (64/108) of those that were still installed were not
      functioning. Multivariate analysis showed that the presence of at least one
      working alarm in the home was associated positively with the number of smoke
      alarms that were originally installed and whether the original occupant was still
      living in the home, and negatively with the length of time since the smoke alarm
      was installed, and whether there was a smoker in the home. Testing of the smoke
      alarms revealed that most non-functioning alarms had missing or dead batteries.
      CONCLUSIONS: Less than a quarter of the originally installed smoke alarms were
      still present and functioning by year 10. These findings have important
      implications for smoke alarm installation programmes.

PMID- 23873498
TI  - Preventing deaths and injuries from house fires: an outcome evaluation of a
      community-based smoke alarm installation programme.
AB  - BACKGROUND: Few studies have examined the impact of community-based smoke alarm
      (SA) distribution programmes on the occurrence of house fire-related deaths and
      injuries (HF-D/I). OBJECTIVE: To determine whether the rate of HF-D/I differed
      for programme houses that had a SA installed through a community-based programme
      called Operation Installation, versus non-programme houses in the same census
      tracts that had not received such a SA. METHODS: Teams of volunteers and
      firefighters canvassed houses in 36 high-risk target census tracts in Dallas, TX,
      between April 2001 and April 2011, and installed lithium-powered SAs in houses
      where residents were present and gave permission. We then followed incidence of
      HF-D/I among residents of the 8134 programme houses versus the 24 346 non
      programme houses. RESULTS: After a mean of 5.2 years of follow-up, the unadjusted
      HF-D/I rate was 68% lower among residents of programme houses versus non
      programme houses (3.1 vs 9.6 per 100 000 population, respectively; rate ratio,
      0.32; 95% CI 0.10 to 0.84). Multivariate analysis including several demographic
      variables showed that the adjusted HF-D/I rate in programme houses was 63% lower
      than non-programme houses. The programme was most effective in the first 5 years
      after SA installation, with declining difference in rates after the 6th year,
      probably due to SAs becoming non-functional during that time. CONCLUSIONS: This
      collaborative, community-based SA installation programme was effective at
      preventing deaths and injuries from house fires, but the duration of
      effectiveness was less than 10 years.

PMID- 23873499
TI  - Number of medications and road traffic crashes in senior Swedish drivers: a
      population-based matched case-control study.
AB  - OBJECTIVE: This study investigated the relationship between the number of
      different medications dispensed (NDMD) to senior drivers and the risk of
      injurious road traffic crashes (RTCs). DESIGN: A matched case-control study with
      data from various population-based national registers was conducted. Cases were
      drivers aged 50-80 years involved in a crash in Sweden between 2005 and 2009.
      Only the first non-alcohol-related RTC was studied. Controls were residents with
      a valid license who did not crash. Four controls were matched by sex, age (year
      and month of birth), and place of residence. Exposure to NDMD prior to the crash
      date was assessed using four time periods: 1-8, 1-15, 1-30 and 1-90 days.
      Conditional logistic regression was used and analyses adjusted for civil status,
      occupation and dispensation of medications affecting the cardiovascular or
      nervous systems (C/N). RESULTS: ORs (95% CI) increased progressively with the
      NDMD. For 1-8 days the OR ranged from 1.15 (1.10 to 1.20) for 1-2 medications to
      1.27 (1.13 to 1.42) for five or more medications. The magnitude of the effect
      declined gradually with longer exposure periods, but remained when five or more
      medications were used. Adjusting for C/N medications resulted in slightly higher
      effects; for 1-8 days it ranged from 1.16 (1.10 to 1.23) for 1-2 medications to
      1.35 (1.17 to 1.56) for five or more, with similar trends by exposure period. The
      highest effects were seen for single crashes and for drivers aged 66-80 years.
      CONCLUSIONS: The NDMD was linked to the likelihood of a senior driver being
      involved in an injurious RTC. The strength of the association steadily increased
      with increased NDMD, especially when medications were taken closer to the index
      date, or when more than five medications were dispensed.

PMID- 23873500
TI  - Current density enhancement in ZnO/CdSe photoelectrochemical cells in the
      presence of a charge separating SnO2 nanoparticles interfacing-layer.
AB  - Photoelectrochemical cells (PECs) of ZnO/CdSe decorated with a charge separating
      SnO2 nanoparticles (NPs) layer of various thicknesses are prepared and
      characterized by using scanning electron microscopy (SEM), electrochemical
      impedance spectroscopy (EIS), UV-visible absorption, energy dispersive X-ray
      analysis spectroscopy (EDX) and incident photon-to-current conversion efficiency
      (IPCE) measurements. A uniform coverage of the SnO2 NPs layer over ZnO/CdSe
      electrode surface is evidenced. The EDX elemental mapping analysis of the
      ZnO/CdSe/SnO2 PECs demonstrates the presence of Sn and O over the surface. A
      remarkable improvement in the light harvesting efficiency confirmed from the IPCE
      measurement, supports an enhancement in current density in the current density
      voltage measurement due to increased electron transport and smaller charge
      recombination. Moreover, these observations are corroborated with the EIS
      measurement as a cell with SnO2 reveals a reduced charge transfer resistance due
      to which the power conversion efficiency is increased from 2.20 to 3.41% i.e. 55%
      compared to the pristine ZnO/CdSe PEC. 

PMID- 23873504
TI  - Association between structural and functional corticospinal involvement in
      amyotrophic lateral sclerosis assessed by diffusion tensor MRI and triple
      stimulation technique.
AB  - INTRODUCTION: We investigated the functional and structural integrity of the
      corticospinal tract (CST) using diffusion tensor imaging (DTI) and the triple
      stimulation technique (TST) in patients with amyotrophic lateral sclerosis (ALS).
      METHODS: Fourteen patients with ALS, 13 healthy controls (HCs), and 6 patients
      with lower motor neuron (LMN) syndrome underwent DTI and TST. RESULTS: The mean
      diffusivity was higher in ALS patients than HCs (P < 0.01). The TST ratio was
      lower in ALS patients compared with HCs (P < 0.001) and in LMN patients compared
      with HCs (P < 0.05). The increase in the mean diffusivity was correlated with the
      decrease in the TST ratio (P < 0.01). CONCLUSIONS: Significant correlations exist
      between the DTI and TST results, indicating both structural and functional
      involvement of the CST in patients with ALS.

PMID- 23873505
TI  - Thermosensitive depot-forming injectable phosphatidylcholine blends tailored for
      localized drug delivery.
AB  - A thermosensitive depot-forming system was developed for sustained and localized
      delivery of the anticancer drug, paclitaxel. The formulation is injectable as a
      melt slightly above the body temperature and forms a solid depot upon cooling to
      37 degrees C. The thermosensitive system was prepared by blending various
      combinations of phosphatidylcholines at specific weight ratios solubilized in
      laurinaldehyde. Of the blends investigated, distearoyl-phosphatidylcholine (DSPC)
      and egg-phosphatidylcholine (ePC) were found to be most miscible. A liquid-to-gel
      phase transition temperature (TC ) of 39 degrees C was observed for the 70:30
      (w/w) DSPC-ePC blend and a TC of 38.4 degrees C with the addition of paclitaxel.
      Blends containing higher concentrations of ePC had a greater degree of swelling
      and weight loss. Furthermore, microscopy revealed an increase in porosity and
      erosion as the amount of ePC was increased in blends incubated in biologically
      relevant media. DSPC-ePC blends provided sustained release of paclitaxel over a
      30-day period and the rate of drug release increased as the amount of ePC
      increased. Overall, the relationships established between the composition and
      properties of the blend may be employed to tailor the thermosensitive injectable
      formulation for localized chemotherapy of solid tumors.

PMID- 23873506
TI  - Topical anti-inflammatory potential of standardized pomegranate rind extract and
      ellagic acid in contact dermatitis.
AB  - The present study evaluated the topical anti-inflammatory potential of a
      standardized pomegranate rind extracts (SPRE) in parallel with its marker
      compound ellagic acid (EA, 13% w/w) against a mouse model of contact dermatitis.
      In the phenol-induced mouse ear edema, topical application of SPRE (5, 2.5, and 1
      mg/ear) and EA (0.65, 0.325, and 0.13 mg/ear, equivalent to its content in SPRE)
      dose-dependently reduced the ear edema with the maximal inhibition of 79.12% and
      73.63%, respectively. Triamcinolone (0.1 mg/ear) and diclofenac (1 mg/ear) as
      reference drugs inhibited the edema by 73.63% and 37.91%. Myeloperoxidase (MPO)
      activity in the mouse ear was also decreased by SPRE and EA up to 69.68% and
      68.79%, respectively. Triamcinolone and diclofenac decreased the MPO activity by
      76.66% and 80.14% similarly. The results indicated that topical application of
      SPRE and EA is promising for use in the treatment of inflammatory skin disorders.

PMID- 23873507
TI  - Eradication of hepatitis C infection: the importance of targeting people who
      inject drugs.

PMID- 23873508
TI  - The efficacy and safety of infliximab used in patients with ankylosing
      spondylitis after unilateral total hip arthroplasty.
AB  - A retrospective study was performed in patients with ankylosing spondylitis (AS)
      from south China, to investigate the efficacy and safety of infliximab after
      total hip arthroplasty (THA). Thirty-two AS patients were divided into two
      groups. The treatmen group recieved infliximab at four weeks after unilateral THA
      (11 patients) and were compare to a control group (21 patients). Patients in the
      control group were treated with traditional medications. Clinical assessment,
      laboratory examinations, and x-rays were performed pre- and postoperatively. The
      BASDAI score decreased more in the infliximab group at six and 12 months after
      THA, as did the CRP and ESR. The contralateral hips without arthroplasty of
      patients in the infliximab group improved significantly compared to the control
      group, in terms of Harris score (HHS), range of motion (ROM) and VAS. However,
      the hips with an arthroplasty in the control group had a better prognosis than
      those without arthroplasty of the infliximab group. Hips with arthroplasty in the
      infliximab group achieved better improvement of HHS than hips without
      arthroplasty in the control group, but not for ROM and pain relief. No
      radiological evidence of prosthetic loosening was found in either group. There
      was no significant difference of the incidence of adverse events between the two
      groups. Compared with THA, AS patients using infliximab only did not obtain as
      good an outcome. Infliximab was shown to be safe and could be effective to
      improve hip function and systemic symptoms. 

PMID- 23873509
TI  - A systematic approach to analyse the sequelae of LCPD.
AB  - The analysis and treatment of hips with healed Legg-Calve-Perthes disease (LCPD)
      differs substantially from the treatment in the acute phase of the disease. More
      specifically, the treating orthopaedic surgeon is often faced with a complex
      three-dimensional pathomorphology of the hip that is difficult to understand and
      correct. To date, none of the current classification systems provide a useful
      decision-making algorithm with regards to the type of surgical intervention
      necessary to improve hip function in patients with sequelae of LCPD. The
      conceptual recognition of the femoroacetabular impingement (FAI) and the ability
      to safely dislocate the hip have revolutionised our diagnostic and therapeutic
      algorithm for joint-preserving surgery of hips with structural residuals of LCPD.
      We present a systematic approach to analyse femoral and acetabular
      pathomorphologic features. The resulting pathomechanisms and the surgical
      treatment options are presented. 

PMID- 23873510
TI  - Assessment of CASP10 contact-assisted predictions.
AB  - In CASP10, for the first time, contact-assisted structure predictions have been
      assessed. Sets of pairs of contacting residues from target structures were
      provided to predictors for a second round of prediction after the initial round
      in which they were given only sequences. The objective of the experiment was to
      measure model quality improvement resulting from the added contact information
      and thereby assess and help develop so-called hybrid prediction methods--methods
      where some experimentally determined distance constraints are used to augment de
      novo computational prediction methods. The results of the experiment were,
      overall, quite promising.

PMID- 23873511
TI  - Update in management of vaginal mesh erosion.
AB  - Mesh erosion is one of the major complications of prolapse surgery conducted by
      transvaginal approach. Following the extensive use of meshes and warning about
      potential complications, a new classification of mesh-related adverse events has
      been proposed. Due to the wide scope of clinical features, no standardized
      approach has been proposed. Surgery is required after failure of conservative
      management, mostly based on mesh partial or total excision by transvaginal route,
      following the classic rules of re-do vaginal surgery. Complex cases are best
      managed in tertiary reference centers. 

PMID- 23873512
TI  - Changes in water quality in agricultural catchments after deployment of
      wastewater treatment plant.
AB  - Insufficient wastewater remediation in small communities and nonpoint source
      pollution are the key factors in determining the water quality of small streams
      in an agricultural landscape. Despite the current extensive construction of
      municipal wastewater treatment facilities in small communities, the level of
      organic substances and nutrients in the recipient catchments has not decreased in
      many areas. This paper analyzes the changes in the water quality of the small
      streams after the deployment of wastewater treatment plants that were designed to
      address sources of pollution from small municipalities. The analysis is based on
      the results from a water quality monitoring network in the small watersheds in
      the Czech Republic. Five rural catchments with one dominant municipal pollution
      source, where a wastewater treatment plant was deployed during the monitoring
      period, were selected according to a predefined set of criteria, from a series of
      317 profiles. Basic water quality indicators were selected for the assessment:
      O2, BOD-5, COD, TOC, conductivity, NH4-N, NO2-N, NO3-N, PT, and PO4-P. Results of
      the analysis showed that the simple deployment of the water treatment facilities
      at these streams often did not lead to a reduction of contamination in the
      streams. The expected post-deployment changes, namely, a significant and
      permanent reduction of stream contamination, occurred only in one catchment,
      whereas in the remainder of the catchments, only marginal changes or even
      increased concentrations of the contaminants were detected. As the critical
      factors that determined the efficiency of wastewater treatment were studied, the
      need for the consideration of the local conditions during the design of the
      facility, particularly regarding the size of the catchments, initial level of
      contamination, proper system of operation, and process optimization of the
      treatment facility, emerged as the important factor.

PMID- 23873513
TI  - Evaluation of land use and water quality in an agricultural watershed in the USA
      indicates multiple sources of bacterial impairment.
AB  - Pathogens are the number one cause of impairments of assessed rivers and streams
      in the USA and pose a significant human health hazard. The Dry Run Creek
      Watershed in Northeast Iowa has been designated as impaired by the State of Iowa
      because of high levels of Escherichia coli bacteria. To investigate the nature of
      this impairment, land use and stream bank assessments were coupled with
      comprehensive water quality monitoring. Physical, chemical, and biological
      parameters were measured at 13 different sites in the watershed, including pH,
      temperature, conductivity, dissolved oxygen, turbidity, total Kjeldahl nitrogen,
      ammonia-N, nitrate + nitrite-N, total phosphorus, and E. coli. In addition,
      benthic macroinvertebrate communities were analyzed at seven sites, and optical
      brightener tests were performed late in the season. Results identified segments
      of the watershed that were more prominent contributors of E. coli, and
      correlations were observed between levels of E. coli and several chemical
      parameters, including ammonia-N, total Kjeldahl nitrogen, and total phosphorus.
      Interestingly, distinct sites emerged as more prominent contributors of these
      elements during rain vs. non-rain events, suggesting different types of sources.
      Both the amount of rainfall and the time elapsed between the rain event and the
      sampling influenced E. coli levels during wet weather conditions. Nitrate +
      nitrite-N displayed a unique response to rain events compared with the other
      parameters, suggesting a different delivery route. Analyses of benthic
      macroinvertebrate communities were consistent with pollution trends.
      Collectively, these data suggest distinct agriculturally related E. coli
      contributions, as well as specific areas and practices for water quality
      improvement strategies. This study can serve as a resource for evaluating
      agricultural watersheds that are impaired for bacteria.

PMID- 23873514
TI  - A covariate-adjusted response-adaptive allocation in clinical trials for a
      general class of responses.
AB  - A class of covariate-adjusted adaptive allocation procedures is developed for a
      general class of responses with an aim to satisfy relevant clinical requirements.
      Some exact and asymptotic properties of the procedures, proposed and a reasonable
      competitor, are studied and compared under the presence of treatment-covariate
      interaction.

PMID- 23873515
TI  - A rapid and efficient way to dynamic creation of cross-reactive sensor arrays
      based on ionic liquids.
AB  - Based on the simple counterion exchange of ionic liquids, a rapid, facile, and
      efficient strategy to create a cross-reactive sensor array with a dynamic tunable
      feature was developed, and exemplified by the construction of a sensor array for
      the identification and classification of nitroaromatics and explosives mimics. To
      achieve a good sensing system with fast response, good sensitivity, and low
      detection limit, the synthesized ionic liquid receptors were tethered onto a
      silica matrix with a macro-mesoporous hierarchical structure. Through the facile
      anion exchange approach, abundant ionic-liquid-based individual receptors with
      diversiform properties, such as different micro-environments, diverse molecular
      interactions, and distinctive physico-chemical properties, were easily and
      quickly synthesized to generate a distinct fingerprint of explosives for pattern
      recognition. The reversible anion exchange ability further endowed the sensor
      array with a dynamic tunable feature as well as good controllability and
      practicality for real-world application. With the assistance of statistical
      analysis, such as principal component analysis (PCA) and linear discrimination
      analysis (LDA), an optimized-size array with a good resolution was rationally
      established from a large number of IL-based receptors. The performed experiments
      suggested that the ionic-liquid-based sensing protocol is a general and powerful
      strategy for creating a cross-reactive sensor array that could find a wide range
      of applications for sensing various analytes or complex mixtures. 

PMID- 23873516
TI  - Quality of life as a predictor of overall survival after breast cancer treatment.
AB  - PURPOSE: To describe quality of life (QoL) in a cohort of surviving women 4 years
      after breast cancer treatment and to analyze its role as a predictor of mortality
      within 2 years. METHODS: This is a prospective cohort study of 544 women who have
      undergone surgical treatment, from 2001 to 2002 and who answered a questionnaire
      about QoL in 2006. After, we conducted a survival study to evaluate the
      association between QoL and mortality within 2 years with the same population. We
      conducted factor analysis between the variables of the scales of function and
      symptoms. Survival analysis was conducted by Kaplan-Meier, and differences in
      survival curves were assessed with the log-rank test, assuming significant
      statistical level of 5 %. The Cox proportional hazards regression model was used
      to explore the relationship between QoL variables (functional scales) and
      prognostic value for survival. RESULTS: The mean age of the women was 59.1 years
      (SD 11.66). The mean of overall QoL score was 75.16 (SD 20.93). Using factor
      analysis, we identified three conditions that made up the construct of QoL in
      this group of patients: social, psycho-emotional, and physical. Social condition
      was the most important factor. After assessment of QoL, the mean survival was 23
      months (SD 3.90). Women who reported worse future perspective had higher chance
      of death compared with women better prospect of future (HR = 3.46; 95 % CI 1.36
      8.79; p value = 0.009). CONCLUSION: Future perspectives were predictors of
      mortality, which reinforce the relevance of social support and psychological
      aspects for these women.

PMID- 23873517
TI  - Polyoxometalate {W18O56XO6} clusters with embedded redox-active main-group
      templates as localized inner-cluster radicals.

PMID- 23873518
TI  - Predictors of poor outcome of decompressive craniectomy in pediatric patients
      with severe traumatic brain injury: a retrospective single center study from
      Pakistan.
AB  - OBJECTIVE: This study aimed to determine the risk factors associated with poor
      outcome of decompressive craniectomy (DC) for severe traumatic brain injury (TBI)
      in pediatric patients. METHODS: This retrospective study is conducted on
      pediatric population (age 1-15 years) presenting with TBI who underwent DC at our
      institute between January 2000 and 2010. Based on Glasgow outcome score (GOS) at
      a minimum follow-up of 5 months, patients were divided into two groups, namely
      poor outcome (GOS 1, 2, and 3) and good outcome (GOS 4 and 5). Records were
      reviewed and analyzed for preoperative and intraoperative predictors. RESULTS: We
      found 25 patients who were eligible as per selection criteria. Mean age at
      presentation was 6 +/- 4 years and there was male preponderance (84%). Fall (60%)
      was the most common mechanism of injury followed by gunshots and road traffic
      accident. On univariate analysis, presenting GCS <=5 (p value = 0.009), delay in
      presentation of more than 150 min (p value = 0.010), DC performed after more than
      4 h of arrival in hospital (p value = 0.042), and intraoperative blood loss
      exceeding 300 ml (p value = 0.001) were significant predictors of poor outcome.
      CONCLUSION: Our study suggests that DC in children is not only a life-saving
      procedure, but also leads to a good functional outcome after severe injury.
      However, patient selection still remains an important aspect, and the above
      mentioned factors should be considered while deciding for DC to improve survival.
      Further prospective studies on larger sample size are warranted to validate our
      results.

PMID- 23873519
TI  - Traumatic retropulsion of T10 vertebra in a 5-year-old boy with involvement of
      neurocentral synchondrosis: a case report and review of the literature.
AB  - STUDY DESIGN: This is a case report of a traumatic retropulsion of the T10
      vertebral body in a 5-year-old boy. OBJECTIVES: This paper aims to describe a
      rare pediatric fracture where there was involvement of the neurocentral
      synchondrosis (NCS) and to evaluate the characteristics of this type of fractures
      in children. SUMMARY OF BACKGROUND DATA: The NCS is the junction between the
      vertebral body and the pedicle bilaterally where the vertebra grows horizontally.
      It closes between 11 and 16 years. It is a known location for spine fracture.
      However, it was mainly reported in children less than 2 years of age secondary to
      nontraumatic injury and at the junction levels of the spine. This is the first
      case of a fracture involving the NCS in a child older than 2 years, due to
      trauma, and in a non-junctional area of the spine. METHODS: This 5-year-old boy
      was involved in a motor vehicle collision where he was ejected from the car. He
      had bilateral lower limb paresthesia and weakness. The fracture involved the
      neurocentral synchondrosis on the left side and impacted the vertebral body into
      the pedicle on the right side. Additionally, there was posterior vertebral
      element injury. He was treated with wide laminectomy and posterior pedicle screw
      instrumentation. RESULTS: At 18 months of follow-up, the patient showed a normal
      neurologic status and a normal alignment of the spine. CONCLUSION: Traumatic
      retropulsion of the thoracic spine with involvement of the NCS is possible in
      young age when exposed to a significant trauma. Restoration of spine alignment
      and normal neurological function could be achieved with a single posterior
      approach. KEY POINTS: - Pediatric fractures are uncommon and tend to affect
      junction areas. - A fracture through the neurocentral synchondrosis is possible
      before the age of closure (11-16 years) with forcible trauma. - Single posterior
      decompression and instrumented fusion is sufficient to restore alignment and
      neurological function.

PMID- 23873520
TI  - Zonisamide: a review of its use in the management of adults with partial
      seizures.
AB  - Oral zonisamide (Zonegran((r))) is a benzisoxazole derivative chemically
      unrelated to other antiepileptic agents. It is indicated in the EU as monotherapy
      in the treatment of partial seizures, with or without secondary generalization,
      in adults with newly diagnosed epilepsy and as adjunctive therapy to other
      antiepileptic drugs (AEDs) in the treatment of adults with partial seizures, with
      or without secondary generalization. In a double-blind, multinational study in
      adults newly diagnosed with partial seizures, shorter-term monotherapy with once
      daily zonisamide was noninferior to that with twice-daily carbamazepine
      controlled release in terms of seizure freedom according to the International
      League Against Epilepsy guidelines, with seizure freedom benefits maintained
      during longer-term therapy. In four randomized, double-blind, placebo-controlled
      studies in adults with refractory partial seizures, shorter-term adjunctive
      therapy with once- or twice-daily zonisamide reduced the frequency of seizures to
      a significantly greater extent than placebo, with antiepileptic efficacy
      sustained following longer-term treatment in this patient population. Zonisamide
      was generally well tolerated in adults with partial seizures participating in
      these studies, with the majority of adverse events being mild or moderate in
      severity. Thus, oral zonisamide as monotherapy or adjunctive therapy to other
      AEDs provides a useful option in the treatment of patients with partial seizures.

PMID- 23873521
TI  - Detection of clinical relapses in multiple sclerosis cohorts: construction and
      validation of a model based on administrative data.
AB  - Multiple sclerosis (MS) is the main cause of chronic disability in young people
      during their most productive years of life and therefore carries a high social
      and economic burden. The present study aimed to: (1) verify the capacity of an
      administrative data source to furnish data for constructing a model able to
      detect the occurrence of clinical relapses in MS patients and (2) validate the
      constructed theoretical model on a set of real-world data. Two MS experts
      identified some administrative variables as proxies of clinical relapses.
      Thereafter, the two MS experts analysed 889 events in 100 MS patients,
      considering only the administrative data relating to these patients, while a
      third neurologist independently analysed the real-world data (documented medical
      history) of the same patients in the same period. Absolute concordance between
      the theoretical model and the real-world data was found in 86 % of the events.
      The model we propose is easily and rapidly applicable, requiring the collection
      of just a few variables that are already present in local health authority
      administrative databases in Italy. It can be used to estimate, with a good level
      of reliability, the occurrence of relapses in various settings. Moreover, the
      model is also exportable to different and larger MS cohorts and could be useful
      for healthcare planning and for evaluating the efficacy of drugs in the real
      world, thus favouring better resource allocation and management.

PMID- 23873522
TI  - Neck-tongue syndrome precipitated by prolonged poor sitting posture.

PMID- 23873523
TI  - Niobium-silica catalysts for the selective epoxidation of cyclic alkenes: the
      generation of the active site by grafting niobocene dichloride.
AB  - Niobium-containing silica materials obtained by deposition via liquid-phase
      grafting or dry impregnation of niobocene(iv) dichloride are active and selective
      catalysts in the epoxidation of alkenes in the presence of aqueous hydrogen
      peroxide. The generation of the catalytically-active Nb species was followed step
      by-step, and investigated using a combined DR-UV-Vis, NIR, Raman, XRD, XANES and
      EXAFS analyses. At the end of the grafting procedure, the nature of the surface
      active species can be described as an oxo-Nb(v) site, tripodally grafted onto the
      silica surface in close proximity to other Nb(v) centres. The liquid-phase
      methodology provides a better dispersion of the metal sites onto the siliceous
      support than the dry-impregnation approach. The niobium-silica catalysts were
      then tested in the epoxidation of cyclohexene and 1-methylcyclohexene, as model
      substrates. 

PMID- 23873525
TI  - Comment on Nietner et al. [Virchows Arch (s2012) 461:259-269].

PMID- 23873524
TI  - Stage-dependent detection of CD14+ and CD16+ cells in the human heart after
      myocardial infarction.
AB  - Monocytes are critically involved in cardiovascular wound healing processes.
      Human monocytes can be classified into two subsets based on the expression of
      CD14 and CD16. Here, we examined the temporal and spatial distribution of CD14+
      and CD16+ cells after myocardial infarction (MI) in human heart and spleen tissue
      and correlated it with markers of cardiac repair. Heart samples obtained at
      autopsy were histologically classified into acute (AMI; n = 11), subacute (SAMI;
      n = 10) and old (OMI; n = 16) MI, or control myocardium (CONTR; n = 8).
      Histochemical analyses revealed marked fibrosis in OMI (p < 0.001 vs. CONTR). The
      adhesion molecule CD56 was also strongly expressed in OMI (p < 0.01 vs. CONTR)
      and found to correlate with fibrosis (p < 0.001). The number of capillaries was
      reduced in OMI (p < 0.01 vs. CONTR; p < 0.05 vs. AMI), whereas the hypoxia
      indicator carbonic anhydrase IX was predominantly expressed in AMI (p < 0.01 vs.
      OMI and CONTR) and SAMI (p < 0.05 vs. OMI and CONTR). The monocyte
      chemoattractrant osteopontin was also more highly expressed in hearts of SAMI
      patients (p < 0.01 vs. CONTR). Numbers of CD14+ monocytes were found to correlate
      with CD16+ cells (p < 0.05) and inversely with fibrosis (p < 0.05). Regarding a
      MI-associated release of monocytes from spleen reservoirs, a non-significant
      reduction of splenic CD14+ and CD16+ cells was detected in subjects with AMI. In
      conclusion, disease stage-specific alterations in CD14+ and CD16 cells in human
      heart may contribute to cardiac repair processes following MI.

PMID- 23873526
TI  - How does a hilly urban environment influence daily physical activity in obese
      individuals?
AB  - BACKGROUND: Increases in physical activity (PA) are promoted by walking in an
      outdoor environment. Along with walking speed, slope is a major determinant of
      exercise intensity, and energy expenditure. The hypothesis was that in free
      living conditions, a hilly environment diminishes PA to a greater extent in obese
      (OB) when compared with control (CO) individuals. METHODS: To assess PA types and
      patterns, 28 CO (22 +/- 2 kg/m2) and 14 OB (33 +/- 4 kg/m2) individuals wore
      during an entire day 2 accelerometers and 1 GPS device, around respectively their
      waist, ankle and shoulder. They performed their usual PA and were asked to walk
      an additional 60 min per day. RESULTS: The duration of inactivity and activity
      with OB individuals tended to be, respectively, higher and lower than that of CO
      individuals (P = .06). Both groups spent less time walking uphill/downhill than
      on the level (20%, 19%, vs. 61% of total walking duration, respectively, P <
      .001). However OB individuals spent less time walking uphill/downhill per day
      than CO (25 +/- 15 and 38 +/- 15 min/d, respectively, P < 0.05) and covered a
      shorter distance per day (3.8 km vs 5.2 km, P < 0.01). CONCLUSIONS: BMI and
      outdoor topography should also be considered when prescribing extra walking in
      free-living conditions.

PMID- 23873539
TI  - Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat
      Harderian gland.
AB  - The rat Harderian gland (HG) is an orbital gland producing a copious lipid
      secretion. Recent studies indicate that its secretory activity is regulated by
      thyroid hormones. In this study, we found that both isoforms of the thyroid
      hormone receptor (Tralpha (Thra) and Trbeta (Thrb)) are expressed in rat HGs.
      Although Thra is expressed at a higher level, only Thrb is regulated by
      triiodothyronine (T3). Because T3 induces an increase in lipid metabolism in rat
      HGs, we investigated the effects of an animal's thyroid state on the expression
      levels of carnitine palmitoyltransferase-1A (Cpt1a) and carnitine
      palmitoyltransferase-1B (Cpt1b) and acyl-CoA oxidase (Acox1) (rate-limiting
      enzymes in mitochondrial and peroxisomal fatty acid oxidation respectively), as
      well as on the mitochondrial compartment, thereby correlating mitochondrial
      activity and biogenesis with morphological analysis. We found that hypothyroidism
      decreased the expression of Cpt1b and Acox1 mRNA, whereas the administration of
      T3 to hypothyroid rats increased transcript levels. Respiratory parameters and
      catalase protein levels provided further evidence that T3 modulates mitochondrial
      and peroxisomal activities. Furthermore, in hypothyroid rat HGs, the
      mitochondrial number and their total area decreased with respect to the controls,
      whereas the average area of the individual mitochondrion did not change. However,
      the average area of the individual mitochondrion was reduced by ~50% in
      hypothyroid T3-treated HGs, and the mitochondrial number and the total area of
      the mitochondrial compartment increased. The mitochondrial morphometric data
      correlated well with the molecular results. Indeed, hypothyroid status did not
      modify the expression of mitochondrial biogenesis genes such as Ppargc1a, Nrf1
      and Tfam, whereas T3 treatment increased the expression level of these genes. 

PMID- 23873540
TI  - An unusual presentation for SOD1-ALS: isolated facial diplegia.

PMID- 23873541
TI  - Development of an enzyme-linked immunosorbent assay for detection of chicken
      osteocalcin and its use in evaluation of perch effects on bone remodeling in
      caged White Leghorns.
AB  - Osteocalcin (OC) is a sensitive biochemical marker for evaluating bone turnover
      in mammals. The role of avian OC is less clear because of the need for a chicken
      assay. Our objectives were to develop an assay using indirect competitive ELISA
      for detecting chicken serum OC and use the assay to examine the effects of
      perches on bone remodeling in caged hens. Anti-chicken OC polyclonal antibody was
      produced by immunization of rabbits with a recombinant OC from Escherichia coli.
      Chicken OC extracted from bone was used as a coated protein, and purified chicken
      OC was used for calibration. The limit of detection of the developed OC ELISA was
      0.13 ng/mL. The intra- and interassay CV were <7 and <12%, respectively. The
      sensitivity of the developed OC ELISA was compared with a commercial Rat-Mid OC
      ELISA in laying hens housed in conventional cages with or without perches. Serum
      samples were collected from 71-wk-old White Leghorn hens subjected to 4
      treatments. Treatment 1 was control chickens that never had access to perches
      during their life cycle. Treatment 2 chickens had perches during the pullet phase
      (0 to 16.9 wk of age), whereas treatment 3 chickens had perches only during the
      egg-laying phase of the life cycle (17 to 71 wk of age). Treatment 4 chickens
      always had access to perches (0 to 71 wk of age). Correlation between the 2
      assays was 0.62 (P < 0.0001). Levels of serum OC using the developed chicken
      ELISA were higher than that detected using the Rat-Mid ELISA (P < 0.0001).
      Results from the chicken ELISA assay showed that hens with perch access had
      higher concentrations of serum OC than hens without perches during egg laying (P
      = 0.04). Pullet access to perches did not affect serum OC levels in 71-wk-old
      hens (P = 0.15). In conclusion, a chicken OC ELISA has been validated that is
      sensitive and accurate with adequate discriminatory power for measuring bone
      remodeling in chickens. 

PMID- 23873542
TI  - Cool perches improve the growth performance and welfare status of broiler
      chickens reared at different stocking densities and high temperatures.
AB  - The present study investigated the interaction of stocking density and cool perch
      availability on broiler chickens raised at high ambient temperature (>30.8
      degrees C). Behavior, live performance, and the incidence of footpad and hock
      burns and abdominal plumage damage were investigated over a 4-wk experimental
      period. A total of 1,152 one-day-old Arbor Acres chicks were subjected to a 2
      (cool perches) * 3 (stocking densities) factorial arrangement of treatments. From
      1 d of age, birds were provided with or without cool perches at each of 3
      stocking densities (12, 16, or 20 birds/m(2); low, medium, or high stocking
      density, respectively) and corresponded to 48, 64, and 80 birds per pen. The
      perch design provided 380 cm of linear perching space in each treatment pen. The
      results showed that high stocking density decreased the growth (P < 0.05) and
      welfare (P < 0.01) of broilers. Cool perch availability increased BW gain and
      feed conversion efficiency of broilers (P < 0.05) regardless of stocking density.
      The birds' use of cool perches increased with age (P < 0.01) and decreased with
      higher stocking density (P < 0.05). The accessibility of cool perches changed
      birds' behavior patterns (P < 0.01) and reduced footpad or hock burns and damage
      to abdominal plumage (P < 0.05). These results suggest that cool perches have a
      favorable effect on the performance and welfare of broilers. 

PMID- 23873543
TI  - The effect of perch availability during pullet rearing and egg laying on
      musculoskeletal health of caged White Leghorn hens.
AB  - A major skeletal problem of conventionally caged hens is increased susceptibility
      to osteoporosis mainly due to lack of exercise. Osteoporosis is characterized by
      a progressive decrease in mineralized structural bone. Whereas considerable
      attention has been given to enriching laying cages, little research has been
      conducted on providing caged pullets with furnishments, in particular perches.
      The objective of the current study was to determine if metal perches during all
      or part of the life cycle of White Leghorns affected hen musculoskeletal health,
      especially at end of lay. Treatments during the pullet phase (hatch to 16.9 wk)
      entailed cages with and without perches. Four treatments were used during the
      laying phase (17 to 71 wk of age). Treatment 1 chickens never had access to
      perches at any point during their life cycle, typical of egg industry practices
      in the United States for conventional cages. Treatment 2 chickens had access to
      perches only during the egg-laying phase, which was from 17 to 71 wk of age.
      Treatment 3 chickens had access to perches only during the pullet phase (0 to
      16.9 wk of age). Treatment 4 chickens had perch access throughout their entire
      life cycle (0 to 71 wk of age). Musculoskeletal health was assessed by measuring
      muscle weights, bone mineralization, bone fracture incidence, and keel bone
      deviations. Muscle deposition of 71-wk-old hens increased when given access to
      perches as pullets. Bone mineralization of 71-wk-old hens also increased if given
      perch access as adults. However, the disadvantage of the adult perch was the
      higher incidence of keel deviations and keel fractures at end of lay. The
      increase in bone mineralization of the keel bone as a result of perch access
      during the pullet and laying phases was not great enough to prevent a higher
      incidence of keel bone fractures at end of lay. Perch redesign and placement of
      perches within the cage to minimize keel fractures and deviations are possible
      solutions. 

PMID- 23873544
TI  - The effects of Forsythia suspensa extract and berberine on growth performance,
      immunity, antioxidant activities, and intestinal microbiota in broilers under
      high stocking density.
AB  - A 42-d experiment was conducted with 276 Arbor Acres broilers (1 d of age,
      weighing 41.1 +/- 1.5 g) to determine the effects of Forsythia suspensa extract
      (FSE) and berberine (BE) on growth performance, immunity, antioxidant activities,
      and intestinal microbiota stocked at high stocking density (28 kg of BW/m(2) as
      the normal density, 46 kg of BW/m(2) as the high density). The feeding program
      consisted of a starter diet from d 1 to 21 of age and a finisher diet from d 22
      to 42. Dietary treatments included (1) negative control group (NC), stocked at
      high density; (2) positive control group (PC), stocked at normal density; (3)
      FSE, NC + 100 mg/kg of FSE; (4) BE, NC + 100 mg/kg of BE; and (5) FSE + BE, NC +
      100 mg/kg of FSE + 100 mg/kg of BE. Birds had free access to diets and water.
      Body weight and feed intake were measured at d 21 and 42. Blood, spleen and
      bursa, and intestinal contents were collected at d 42 for analysis. The results
      showed that growth performance did not differ among treatments in the starter
      period; however, in the finisher and overall periods, birds in FSE + BE, FSE, BE,
      and PC had greater final BW, ADG, and ADFI than the birds in NC (P < 0.05). The
      birds in FSE + BE, FSE, BE, and PC had greater bursa weight, bursa weight/BW
      ratio, serum total antioxidant capacity, and superoxide dismutase activity than
      birds in NC (P < 0.05). The FSE + BE, FSE, and BE birds had lower serum
      malondialdehyde level than NC birds (P < 0.05). The FSE + BE, FSE, BE, and PC
      birds had lower counts of Escherichia coli but greater Lactobacillus in the cecum
      than that of NC birds (P < 0.05). Dietary supplementation with FSE, BE, or both
      can improve the growth performance possibly by enhancing immunity, reducing
      oxidative stress, and promoting intestinal colonization by healthy microbiota of
      broilers under high stocking density. 

PMID- 23873545
TI  - Changes of several acute phase factors in broiler chickens in response to
      infectious bronchitis virus infection.
AB  - This study was performed to clarify the acute phase response following infectious
      bronchitis virus inoculation. Ninety clinically healthy 1-d-old Ross chicks were
      randomly assigned into 2 groups: control (n = 20) and infected group (n = 70). At
      the age of 20 d, all birds in the infected group were challenged intranasally
      with allantoic fluid containing 10(5) embryo lethal dose (ELD50)/0.1 mL of the
      infectious bronchitis virus. Blood samples were collected from 20 clinically
      healthy and 70 infected chicks at prior and 1, 2, 3, 5, 7, 11, 13, 15, and 20 d
      postinoculation. On d 1, 7, and 11 postinoculation 4 chickens from the
      experimental group and 2 chickens from the control group were randomly selected.
      Their trachea, lungs, and cecal tonsil were collected for virus detection and
      quantitation by real-time reverse-transcription PCR assay. In the serum the acute
      phase proteins (haptoglobin and serum amyloid A), pro-inflammatory cytokines
      (interferon-gamma and tumor necrosis factor-alpha), and serum sialic acid (total,
      TSA; lipid-bound, LBSA; and protein-bound, PBSA) concentrations were measured
      using validated standard procedures. All variables were significantly higher in
      the infected birds after virus inoculation compared with the healthy group (P <
      0.05). There were positive correlations between all variables in the infected
      group. Correlation coefficients were significantly positive between haptoglobin
      and interferon-gamma, LBSA and TSA, and TSA and LBSA (P < 0.05). There were
      positive correlations among viral RNA and all studied variables; however, these
      correlations were not statistically significant (P > 0.05). 

PMID- 23873546
TI  - The effects of necrotic enteritis, aflatoxin B1, and virginiamycin on growth
      performance, necrotic enteritis lesion scores, and mortality in young broilers.
AB  - The effects of increasing aflatoxin B1 concentration (0, 0.75, 1.5 mg/kg) on
      broilers with or without necrotic enteritis or virginiamycin were determined. In
      the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3
      * 2 * 2 factorial arrangement) with 8 replications. Intestines of 5 birds per pen
      were examined for lesions on d 21. Birds were allowed to consume feed and water
      ad libitum. Aflatoxin was included in the diets from d 0. All birds received a
      10* dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis
      was being induced were on Clostridium perfringens pathogen (CPP) contaminated
      litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer
      feed:gain, increased mortality, and higher lesion scores. Inducing necrotic
      enteritis increased lesion scores and decreased feed intake and gain. Adding
      virginiamycin to the diets improved gain, feed intake, feed conversion, and
      decreased mortality. There was a 3-way interaction (aflatoxin * virginiamycin *
      CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and
      virginiamycin were dependent on aflatoxin concentration. In the absence of
      aflatoxin virginiamycin increased gain but was unable to prevent the growth
      suppression caused by CPP. At 0.75 mg/kg of aflatoxin virginiamycin no longer
      increased growth in non-CPP challenged birds but was able to increase growth in
      CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin
      increased gain in non-CPP-challenged birds but challenging birds with CPP had no
      effect on gain. Virginiamycin improved overall feed conversion with the greatest
      improvement at 1.5 mg/kg (aflatoxin * virginiamycin, P < 0.05). Aflatoxin
      increased lesion scores in unchallenged birds but not in challenged birds
      (aflatoxin * CPP, P < 0.001). Aflatoxin and necrotic enteritis decrease broiler
      performance and interact to decrease weight gain, virginiamycin helps improve
      gain in challenged birds at 0.75 mg/kg of aflatoxin, but not at 1.5 mg/kg of
      aflatoxin. 

PMID- 23873547
TI  - Litter aeration and spread of Salmonella in broilers.
AB  - Litter quality in the poultry sector is one of the main parameters of health,
      productivity, and animal welfare. Therefore, innovative management methods have
      been developed to improve the quality of litter. One of them is litter aeration
      (LA) by tumbling. However, there is little information related to the effect of
      this technique on the spreading of pathogens of public health importance such as
      Salmonella. In this context, the objective of this study was to determine the
      epidemiology of Salmonella in poultry farms, when serial LA were implemented
      during the rearing cycle of broilers. For this purpose, an experimental broiler
      farm with 3 identical rooms was used in the study. Two rooms were assigned to the
      LA treatment, and the other one served as the control room. Environmental samples
      were taken in poultry houses after LA in 4 consecutive weeks at the end of the
      cycle. All samples collected were analyzed according to the standards of the
      International Organization for Standardization (ISO 6579:2002, Annex D). The
      results of this study showed that in the control and treated rooms, the
      percentage of positive samples for Salmonella decreased in the first 3 LA
      sessions (LA 1, LA 2, and LA 3). However, in the last LA session of rearing (LA
      4), the percentage of positive samples increased from 8.2 to 33.2% in the control
      room instead the treated rooms where the positive samples decreased (P = 0.017).
      Thus, the aeration of the litter as litter management technique in poultry
      broiler production does not increase the shedding or the spread of Salmonella
      throughout broiler houses. In addition, it could be an effective technique to
      reduce the infective pressure of this bacterium in several areas of the farm or
      in certain moments of the rearing period with more risk of multiplication and
      spreading of Salmonella. 

PMID- 23873548
TI  - Geographical distribution of low pathogenic avian influenza viruses of domestic
      poultry in Vietnam and their genetic relevance with Asian isolates.
AB  - From the avian influenza virus (AIV) outbreaks and market surveillances in
      Vietnam during November 2011 and March 2012, a total of 196 AIV were isolated.
      Although H5N1 highly pathogenic avian influenza (HPAI) was the most prevalent
      subtype in Vietnam, 57 low pathogenic avian influenza (LPAI) viruses were
      identified from mainly domestic ducks and some chickens. Of note, various
      subtypes of LPAI viruses were isolated from domestic ducks in Vietnam: H3 (n =
      16), H4 (n = 4), H6 (n = 24), H7 (n = 1), and H9 (n = 10). Geographically, the
      LPAI viruses were identified in different regions of Vietnam. Phylogenetic
      analysis of HA and NA genes in LPAIV in Vietnam showed that some H3 (group I) and
      H4 subtypes AIV clustered with the viruses of several Asian isolates from
      domestic poultry and wild birds. However, the H6, H9, and some H3 (group II and
      III) subtypes AIV were closely related to isolates from domestic poultry in
      Southern China. In addition, whereas the N2 and N6 subtypes AIV belonged to the
      Eurasian lineage, the N8 subtype AIV was classified to be both of Eurasian and
      American lineage. These findings revealed that the regional trade and wild birds
      play a key role transmission of LPAIV in domestic ducks in Vietnam. Further
      surveillance at the intercountry level is needed to understand the epidemiology
      of these viruses and to cope with emergence of novel AIV types. 

PMID- 23873549
TI  - Genetic parameters of natural antibody isotypes and survival analysis in beak
      trimmed and non-beak-trimmed crossbred laying hens.
AB  - Natural antibodies (NAb) are important humoral components of innate immunity. As
      the first line of defense, NAb provide protection against infection and support
      adaptive immunity. An earlier study indicated that serum levels of NAb isotypes
      IgM and IgG at a young age were predictive for survival in non-beak-trimmed
      purebred laying hens during the laying period. In the present study, genetic
      parameters of NAb isotypes were estimated and relationships between survival and
      NAb isotypes levels in crossbred laying hens were investigated. In total, 1,555
      beak-trimmed and 1,169 non-beak-trimmed crossbred laying hens were used. Genetic
      parameters of IgM and IgG titers binding keyhole limpet hemocyanin at 24 wk of
      age were estimated with a linear animal model. The heritabilities of NAb isotypes
      IgG and IgM were 0.21 (SE = 0.04) and 0.26 (SE = 0.04), respectively. The genetic
      correlation between IgG and IgM isotypes was 0.43 (SE = 0.11). These results
      indicated that NAb isotype titers were heritable traits in the crossbred laying
      hens. Both NAb isotypes can be selected for simultaneously because the detected
      positive genetic correlation (0.43, SE = 0.11) between them is positive. Both row
      and level of the cage were indicated to be associated environmental factors for
      NAb isotype titers. Different from an earlier study with purebred hens, survival
      analysis showed no significant associations of survival with NAb isotype titers
      in beak-trimmed or non-beak-trimmed crossbred hens. Non-health-related causes of
      mortality, especially in birds with intact beaks, overruled the anticipated
      relationships between NAb isotype titers and survival. 

PMID- 23873550
TI  - Development and field application of a competitive enzyme-linked immunosorbent
      assay for detection of Newcastle disease virus antibodies in chickens and ducks.
AB  - A competitive enzyme-linked immunosorbent assay (C-ELISA) using a baculovirus
      expressed recombinant nucleocapsid protein antigen (rNDV-N) and an rNDV-N
      specific monoclonal antibody (5B3) was developed for the detection of Newcastle
      disease virus (NDV) antibodies, and its diagnostic performance was evaluated. The
      specificity and sensitivity of the C-ELISA was found to be 98.4 and 98.9%,
      respectively, for chickens, and 98.2 and 97.9% for ducks. However, the C-ELISA
      showed weak cross-reaction with hyperimmune antisera to some other avian
      paramyxovirus serotypes. In all experimentally vaccinated chickens,
      seroconversion rates at 7 d postinoculation were 100 and 40% when measured by C
      ELISA and hemagglutination inhibition (HI), respectively. In field trials, the C
      ELISA showed positive results in 98.9% of HI-positive sera and 40.8% of HI
      negative sera from NDV-vaccinated chickens (n = 705). In domestic ducks (n = 158)
      from NDV-positive duck farms (n = 8), the positive rates according to C-ELISA
      were significantly higher than those according to the HI test. At the same time,
      98.1% of ducks (n = 209) from NDV-negative duck farms (n = 11) were also negative
      by C-ELISA. Our results indicate that C-ELISA could be a useful alternative to HI
      testing for detecting NDV antibodies in different avian species such as chickens
      and ducks. 

PMID- 23873552
TI  - Restriction fragment length polymorphism analysis of multiple genome regions of
      Korean isolates of infectious laryngotracheitis virus collected from chickens.
AB  - This study was conducted to characterize infectious laryngotracheitis (ILT)
      viruses isolated from poultry in South Korea using RFLP analysis of PCR products.
      Seven wild-type Korean isolates from commercial chicken farms collected between
      1986 and 2012 were compared with 3 imported commercial vaccine strains [LT Blen
      (Hudson strain, United States), Laryngo Vac (Cover strain, United States), and
      Nobilis ILT (Serva strain, France)] and a Korean chicken embryo origin (CEO)
      vaccine strain [ILT-VAC (Gyeonggi97 strain, Korea)]. Six of the field isolates
      were highly virulent viruses, and the Kr12AD37 isolate was considered an
      attenuated type according to Han's RFLP method. These virulent Korean ILT viruses
      were divided into 3 classes (class I, II, and III). The Kr12AD37 isolate was
      found to have the same RFLP pattern as the Korean CEO vaccine strain, and both of
      these strains were different from the 3 foreign vaccine strains. The results
      suggest that the Korean CEO vaccine strain has been responsible for recent
      outbreaks, and the characterization of ILT viruses by RFLP was useful for
      diagnosis by providing epidemiological information. 

PMID- 23873551
TI  - Expression of hypoxia-inducible factor 1alpha mRNA in hearts and lungs of broiler
      chickens with ascites syndrome induced by excess salt in drinking water.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a ubiquitously expressed heterodimeric
      transcription factor that mediates adaptive responses to hypoxia in all nucleated
      cells of metazoan organisms. Hypoxia-inducible factor 1alpha is involved in the
      pathogenesis of pulmonary hypertension in humans and animals, but whether HIF
      1alpha is associated with the development of pulmonary hypertension syndrome
      (also known as ascites syndrome, AS) in broiler chickens has not been determined.
      In the present paper we addressed this issue by measuring the expression of HIF
      1alpha mRNA in hearts and lungs of broiler chickens with AS induced by excess
      salt in drinking water. We conducted 2 experiments. The first experiment was used
      to observe the effects of excess salt on AS incidence. The results indicated that
      total incidence (20%) of AS in excess salt group (receiving 0.3% NaCl in drinking
      water) was much higher compared with the control group (receiving tap water) over
      a 43-d time course (P < 0.05). In the second experiment, we determined mean
      pulmonary arterial pressure (mPAP), ascites heart index (AHI), and expression of
      HIF-1alpha mRNA in lungs and hearts of broiler chickens after the excess salt
      treatment. Our results showed that excess salt induced pulmonary hypertension
      (indicated by higher mPAP) and right ventricular hypertrophy (greater ascites
      heart index) in broiler chickens. Meanwhile, the expression levels of HIF-1alpha
      mRNA in lungs and hearts were significantly increased at different time points in
      the excess salt group compared with the control group. Linear correlation
      analysis showed that the expression of HIF-1alpha mRNA in lungs was significantly
      positively correlated with mPAP (correlation coefficient = 0.79, P < 0.001),
      demonstrating that expression of HIF-1alpha mRNA was gradually increased in the
      excess salt group with the increase of pulmonary arterial pressure. In addition,
      the ascitic chickens showed significantly higher transcriptional levels of HIF
      1alpha in hearts and lungs, compared with the age-matched healthy chickens,
      respectively. Our findings hinted that HIF-1alpha might be associated with the
      development of AS induced by excess salt in drinking water in broiler chickens. 

PMID- 23873554
TI  - Effect of feeding low-oil distillers dried grains with solubles on the
      performance of broilers.
AB  - Manufacturers of distillers dried grains with solubles (DDGS) are changing
      practices to extract corn oil from DDGS in the process of ethanol production. The
      resulting product is called low-oil DDGS (LO-DDGS) and may be included in broiler
      diets. Two LO-DDGS and one unextracted DDGS were used in a broiler performance
      trial to determine maximum levels of inclusion without detrimental effects. Corn-
      and soybean meal-based mash diets were used with different DDGS samples included
      at 10 or 20%. Six hundred thirty Cobb 500 male by-product chicks were randomly
      assigned to 6 replicate pens containing 15 chicks each and fed diets from 0 to 18
      d of age. There was a significant interaction between source and level on BW at d
      11 and 18 when 10 and 20% of LO-DDGS was included compared with the control
      group. There was also a significant effect of source and level interaction on BW
      at d 18 (P < 0.05). Feed efficiency from d 0 to 18 was improved when 10% LO-DDGS
      was used compared with 20% inclusion. Abdominal fat pad weights were higher when
      LO-DDGS samples were included at 10 or 20% compared with the control group. There
      was a significant effect of DDGS source and level on fat pad weights (P < 0.05).
      Producers may achieve an increase in performance when including 10% LO-DDGS in
      broiler diets. Up to 20% inclusion levels may have no detrimental effects on
      performance parameters compared with a standard corn-soybean diet. 

PMID- 23873553
TI  - Effect of thymol and carvacrol feed supplementation on performance, antioxidant
      enzyme activities, fatty acid composition, digestive enzyme activities, and
      immune response in broiler chickens.
AB  - This trial was conducted to evaluate the effects of dietary supplementation of
      phytogenic product containing an equal mixture of thymol and carvacrol at 4
      levels (0, 60, 100, and 200 mg/kg of diet) on performance, antioxidant enzyme
      activities, fatty acid composition, digestive enzyme activities, and immune
      response in broiler chickens. Each of the 4 diets was fed to 5 replicates of 12
      chicks each from d 0 to 42. The inclusion of thymol + carvacrol linearly
      decreased (P < 0.05) feed intake, but the highest (P < 0.05) BW gain (ADG) and
      feed efficiency was observed in broilers offered 200 mg/kg of phytogenic product.
      The phytogenic product linearly increased (P < 0.05) superoxide dismutase and
      glutathione peroxidase activities and decreased (P < 0.05) malondialdehyde level
      in thigh muscle at d 42 and serum and liver at d 24 and 42. Total saturated fatty
      acids were depressed (P < 0.05) and total polyunsaturated fatty acid and n-6 were
      linearly increased (P < 0.05) in serum and thigh by the inclusion of phytogenic
      product compared with the control diet. Supplementation with thymol + carvacrol
      also increased intestinal and pancreatic trypsin, lipase, and protease activities
      in 24-d-old (linear, P < 0.05) but not in 42-d-old birds. Thymol + carvacrol
      modified (linear, P < 0.05) immune response by increasing hypersensitivity
      response, total and IgG anti-sheep red blood cell titers, and decreasing
      heterophil to lymphocyte ratio compared with the control group. However,
      hematological parameters and lymphoid organ weight were not affected by thymol +
      carvacrol. Thus, feed supplementation with thymol + carvacrol enhanced
      performance, increased antioxidant enzyme activities, retarded lipid oxidation,
      enhanced digestive enzyme activities, and improved immune response of broilers. 

PMID- 23873555
TI  - Lipid metabolism of commercial layers fed diets containing aflatoxin, fumonisin,
      and a binder.
AB  - Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers,
      leading to huge economic losses. This experiment was conducted to determine the
      effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in
      combination, on the lipid metabolism in commercial layers and investigate the
      efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of
      these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were
      randomized into a 3 * 2 + 1 factorial arrangement (3 diets with no binder
      containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU;
      and a control diet with no mycotoxins and binders), totaling 7 treatments. The
      hens contaminated with AF showed the characteristic effects of aflatoxicosis,
      such as a yellow liver, resulting from the accumulation of liver fat, lower
      values of plasma very low-density lipoprotein and triglycerides, and higher
      relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of
      FU were not observed in this study. On the other hand, the FU caused a reduction
      in small intestine length and an increase in abdominal fat deposition. The glucan
      based binder prevented some of the deleterious effects of these mycotoxins,
      particularly the effects of AF on hepatic lipid metabolism, kidney relative
      weight, and FU in the small intestine. 

PMID- 23873556
TI  - Supplementation of direct-fed microbials as an alternative to antibiotic on
      growth performance, immune response, cecal microbial population, and ileal
      morphology of broiler chickens.
AB  - An experiment was conducted to investigate the supplementation of direct-fed
      microbials (DFM) as an alternative to antibiotics on growth performance, immune
      response, cecal microbial population, and ileal morphology of broiler chickens. A
      total of 800 one-day-old male broiler chicks (Ross * Ross) were randomly allotted
      to 4 dietary treatments with 4 replicate pens per treatment (50 birds/replicate
      pen). The 4 dietary treatments fed for 35 d were a corn-soybean meal basal diet
      (control); control plus 0.1% virginiamycin, as an antibiotic growth promoter
      (AGP); control plus 0.1% direct-fed microbials that contained Lactobacillus
      reuteri (DFM 1); and control plus 0.1% direct-fed microbials that contained a
      mixture of L. reuteri, Bacillus subtilis, and Saccharomyces cerevisiae (DFM 2).
      Results showed that dietary AGP and DFM supplementation significantly increased
      (P < 0.05) the BW gain of broilers during 0 to 21 d. The feed intake was reduced,
      whereas the feed conversion was improved significantly when birds were fed DFM 2
      at 0 to 7 d of age. The white blood cell and monocyte levels were significantly
      higher in the DFM 2 group compared with the control. In addition, feeding DFM
      significantly (P < 0.05) increased the plasma immunoglobulin levels where a
      higher level was observed in DFM 2 compared with those of the other treatments.
      Neither DFM nor AGP treatments affected the cecal Lactobacillus and Salmonella
      content; however, cecal Escherichia coli content significantly decreased in
      broiler chickens fed DFM and AGP. The ileal villus height, and width and total
      thickness of muscularis externa were significantly increased when birds were fed
      DFM compared with AGP and control. These results indicate that the dietary
      supplementation of DFM increases the growth performance of birds at an early age,
      stimulates the immune response, decreases the number of E. coli, and improves the
      ileal morphology of broiler chickens. Thus, DFM that contained a mixture of
      several beneficial microorganisms could be a viable alternative to antibiotics in
      the broiler diets. 

PMID- 23873557
TI  - Effects of growth patterns and dietary crude protein levels during rearing on
      body composition and performance in broiler breeder females during the rearing
      and laying period.
AB  - The combined effects of growth pattern (GP) and dietary CP level during rearing
      (2 to 22 wk of age) on body composition and performance were investigated in
      broiler breeder females from 0 to 40 wk of age. One-day-old pullets (n = 768)
      were randomly allotted to 48 pens according to 2 growth patterns (standard = SGP
      and high = HGP) and fed using 1 of 3 dietary CP levels (high = CPh, medium = CPm,
      and low = CPl). From 19 to 22 wk of age, feeding level was gradually adjusted to
      obtain a similar target BW for all birds, and then until 40 wk of age, all birds
      received similar amounts of a standard breeder diet. During the rearing period,
      the HGP pullets were fed a higher feed intake level (6.5%) than SGP pullets. To
      meet BW targets at 22 wk of age, feed intake from d 14 onward had to be increased
      for the CPm (4.6%) and CPl (10.0%) treatments. Breast muscle percentages of HGP
      and SGP pullets were similar at any age, although abdominal fat pad at 20 wk was
      0.18% higher for HGP pullets. Pullets fed the CPl diet had a lower breast muscle
      percentage compared with pullets fed the CPm and CPh diets (0.46 and 0.85% at wk
      10, 0.81 and 1.45% at wk 20, respectively). Abdominal fat pads in CPl pullets
      were 0.18 and 0.22% (wk 10), and 0.24 and 0.42% (wk 20) higher compared with CPm
      and CPh pullets, respectively. At 40 wk of age, no effects on breast muscle and
      abdominal fat pad were found among all treatments. Egg production, sexual
      maturation, and egg weight were not affected by GP and CP levels during rearing.
      It was concluded that a low CP diet during rearing decreased breast muscle and
      increased abdominal fat pad, whereas a high GP only increased abdominal fat pad,
      at the end of the rearing period. Decreasing dietary CP level seems to be more
      effective in increasing abdominal fat pad than increasing GP. 

PMID- 23873558
TI  - Assessment of a bacterial 6-phytase in the diets of broiler chickens.
AB  - Two 21-d broiler experiments were conducted to assess the efficacy of a bacterial
      6-phytase expressed in Aspergillus oryzae on growth performance, nutrient
      utilization, and intestinal molecular markers. Two hundred forty birds in 5
      treatments (experiment 1) or 256 birds in 4 treatments (experiment 2) were used.
      The treatments included a negative control diet that was marginally deficient in
      P (NC) or NC plus tricalcium phosphate, 500, 1,000, or 2,000 phytase units/kg
      (experiment 1), and NC or NC plus monocalcium phosphate, 500 or 1,000 phytase
      units/kg (experiment 2). In both experiments, excreta were collected on d 19 to
      21, whereas birds and feed were weighed and ileal digesta collected on d 21. For
      experiment 1, mucosa scraping was collected from the duodenum, jejunum, and ileum
      from all birds for quantification of expression level of gut level inflammatory
      cytokines, Toll-like receptors, and phosphate transporter (NaPi-IIb). In both
      experiments, tricalcium phosphate, monocalcium phosphate, and phytase
      supplementation improved (P < 0.05) weight gain and percentage tibia ash.
      Phosphorus and Ca retention and phytic acid disappearance improved (P < 0.05)
      with phytase supplementation (experiment 1) and there was an increase (P < 0.01)
      in Ca and P retention in response to phytase supplementation (experiment 2).
      Diets did not affect the expression of gut level cytokines, Toll-like receptors,
      or the mucin gene. Phytase supplementation tended to decrease (P < 0.10) the
      expression of NaPi-IIb. It was concluded from these studies that the bacterial 6
      phytase was effective in enhancing growth of broilers receiving low-P diets as
      well as in increasing efficiency of P utilization and phytic acid degradation. 

PMID- 23873559
TI  - Linking ileal digestible phosphorus and bone mineralization in broiler chickens
      fed diets supplemented with phytase and highly soluble calcium.
AB  - The objectives of this study were to determine the ileal digestibility of P in
      potassium phosphate, phytase-related ileal digestible P release, bone
      mineralization-based ileal digestible P equivalency of phytase, and phytase
      related efficiency of ileal digestible P utilization for bone mineralization in
      broiler chickens at 2 dietary concentrations of highly soluble Ca (HSC). Birds
      were sorted by BW at d 15 posthatch and assigned to 8 cages per diet with 8 birds
      per cage. Twelve diets were arranged in a 2 * 6 factorial of HSC at 5 or 6 g/kg
      and P supply treatment at 6 levels consisting of 4 added P levels (P from KH2PO4
      added at 0, 0.7, 1.4, or 2.1 g/kg of diet) or 2 added phytase levels (500 or
      1,000 phytase units). On d 24 posthatch, ileal digesta were collected for ileal P
      digestibility (IPD) determination and the left tibia was collected from the 4
      heaviest birds in each cage for bone ash determination. Weight gain, G:F, and
      tibia ash were higher (P < 0.05) at 5 than at 6 g of HSC/kg. Added P from KH2PO4
      or added phytase linearly increased (P < 0.001) weight gain, G:F, tibia ash, and
      IPD. The IPD of KH2PO4 derived from multiple linear regressions of digestible on
      total P intake for the diets without added phytase showed a reduction (P < 0.05)
      from 89.5 to 84.5% with increased HSC from 5 to 6 g/kg. Polynomial regressions of
      digestible P intake on phytase intake indicated that 1,000 units of added phytase
      released 1.701 or 1.561 g of digestible P in diets containing 5 or 6 g of added
      HSC/kg, respectively. Polynomial regressions of tibia ash on digestible P or
      phytase intake in diets containing 5 or 6 g of added HSC/kg at 1,000 phytase
      units gave digestible P equivalency of 1.487 or 1.448 g, respectively. Thus,
      phytase-related efficiency of ileal digestible P utilization for bone
      mineralization was 87.4 and 92.8% in diets containing 5 or 6 g of added HSC/kg,
      respectively. 

PMID- 23873560
TI  - Effects of in ovo feeding of carbohydrates on hatchability, body weight, and
      energy status in domestic pigeons (Columba livia).
AB  - The effects of in ovo feeding of carbohydrates on hatchability, BW, yolk sac
      weights (YSW), pectoral muscle weights (PMW), liver and pectoral muscle glycogen
      concentration, serum glucose level, and hepatic glucose-6-phosphatase activity of
      domestic pigeons, hatched from eggs laid by a 40-wk-old breeder flock, were
      investigated. At 14.5 of incubation, fertile eggs were injected with 200 MUL of
      1.5% maltose (M) + 1.5% sucrose (S), 2.5% M + 2.5% S, 3.5% M + 3.5% S, or 4.5% M
      + 4.5% S in 0.75% saline, with controls not injected. Results showed that in ovo
      injection with 1.5% M + 1.5% S or 2.5% M + 2.5% S increased the hatchability
      compared with the control, whereas injection of 4.5% M + 4.5% S decreased the
      hatchability. The BW at hatch was quadratic, and BW was maximized by injecting
      2.5% M + 2.5% S. The YSW at hatch decreased linearly by the injection with 3.5% M
      + 3.5% S compared with the control group. In ovo injection of 2.5% M + 2.5% S
      increased the PMW at hatch. There were no significant differences between any of
      the treatment groups for liver glycogen reserves. Serum glucose level at hatch
      was quadratic, and the glucose level was maximized between supplemental 2.5% M +
      2.5% S and supplemental 3.5% M + 3.5% S. The pectoral muscle glycogen reserves
      increased quadratically as supplemental carbohydrates increased, and the response
      was maximized by injecting 2.5% M + 2.5% S. In conclusion, the present results
      demonstrate that the injected carbohydrates are available for use and storage. In
      ovo feeding of carbohydrates, especially at the level of 2.5% M + 2.5% S, on 14.5
      d of incubation can improve the hatchability, BW, and PMW by elevating the
      pectoral muscle glycogen reserves in domestic pigeons at hatch. Results also
      suggested that in ovo injection of carbohydrates could increase the yolk sac
      nutrient utilization and hence might enhance the pigeon enteric development. 

PMID- 23873561
TI  - The effect of microbial phytase and myo-inositol on performance and blood
      biochemistry of broiler chickens fed wheat/corn-based diets.
AB  - A total of 1,200 Ross broiler chickens were used in 2 separate feeding studies to
      explore the effect of myo-inositol (MYO) and phytase on performance and blood
      biochemistry of broilers fed diets formulated to be either adequate or
      insufficient in Ca and digestible P (dP). Supplementation of diets that were
      formulated to be insufficient in Ca and dP with MYO resulted in improved BW gain
      and feed conversion ratio in both experiments. However, these effects were most
      pronounced in the finisher phase, and moderate negative effects were observed
      during the starter period. Supplementation of the diet with microbial phytase
      improved BW gain and feed conversion ratio to a similar extent as was observed
      with MYO, and there was a degree of subadditivity between the 2 additives. Blood
      glucose concentrations were increased by both MYO and phytase, though possibly by
      different mechanisms, because insulin concentrations were not directly relatable
      to circulating glucose levels, especially when both MYO and phytase were applied
      simultaneously. The increase in blood glucose concentrations with MYO and phytase
      was most pronounced in the diet with a lower Ca and dP concentration. It can be
      concluded that dietary supplementation with MYO or phytase was effective in
      improving performance of commercial broiler chickens. However, further work is
      required to explore complex ontogenetic effects of MYO and possible involvement
      of both MYO and phytase in Na-dependent transport mechanisms. 

PMID- 23873562
TI  - Comparative analysis of Campylobacter populations within individual market-age
      broilers using Fla gene typing method.
AB  - Campylobacter species is the most common human pathogen causing gastrointestinal
      infections in humans, and poultry is considered a major source of this pathogen.
      In this project, we aim to study the genetic diversity of Campylobacter
      populations within individual chickens using cecal samples to understand the
      nature of intestinal colonization in chickens by Campylobacter species.
      Genotyping was conducted based on the DNA sequence of short variable regions
      (SVR) in the flaA gene. Cecal samples were collected from 9 market-age broiler
      chickens and used for isolation of Campylobacter genomic DNA. The SVR fragments
      of 400 bp were amplified using SVR-specific primers, cloned, and sequenced.
      Sequencing results obtained from 86 clones (~10 clones/bird) showed that on an
      average 23.25% of clones had mutations within individuals. The mutations did not
      show any consistent pattern, suggesting a random nature of the mutations. When
      translated SVR sequences were analyzed, on average 20.57% of strains carried
      altered amino acid sequences in SVR within individuals. Four translated sequences
      had nonsense mutations to produce truncated proteins. These results suggest that
      there are multiple genotypes colonizing in a cecum and the occurrence of
      truncated FlaA protein may represent a novel mechanism for evasion of adaptive
      immune responses. 

PMID- 23873563
TI  - Effect of relative humidity during incubation at a set eggshell temperature and
      brooding temperature posthatch on embryonic mortality and chick quality.
AB  - Previous studies have shown that RH during incubation of chicken eggs influences
      water loss from the egg and embryonic mortality. In those studies, eggshell
      temperatures (EST) were not monitored or controlled. Because RH influences the
      egg's heat loss through evaporation, EST might have been different between RH
      treatments, influencing embryonic mortality and development. To eliminate the
      effect of EST, in the current study eggs were incubated at an EST of 37.8 degrees
      C from embryonic d (E) 0 until E18 and at a high (55 to 60%) or low (30 to 35%)
      RH from E2 until hatch. Embryonic mortality, hatch curve, and several chick
      quality characteristics (length, weight, navel quality, organ weights, and DM of
      the yolk free body mass and yolk) were determined on E18 and at hatch. Low RH
      increased egg weight loss between E0 and E18 (+3.0%) and third week embryonic
      mortality (+3.0% of fertile eggs) and decreased hatch of fertile eggs (-2.9% of
      fertile eggs) compared with high RH. Hatch duration and chick quality
      characteristics did not differ between RH treatments. To assess the effect of RH
      during incubation on posthatch performance under suboptimal conditions,
      hatchlings were brooded at a normal (35.0 degrees C at d 0, decreasing to 27.0
      degrees C at d 4) or cold (27.8 degrees C at d 0, decreasing to 25.6 degrees C at
      d 4) temperature until 4 d posthatch. Incubation RH and brooding temperature
      significantly interacted with posthatch growth but not development. Both low and
      high RH * cold brooding temperature resulted in lower (-6.9 and -6.0 g,
      respectively) BW than high RH * normal brooding temperature at 4 d of age. The
      cold brooding temperature resulted in lower daily feed intake (-1.3 g/chick) than
      the normal brooding temperature. In conclusion, incubating eggs at a low RH
      compared with a high RH and maintaining the EST at 37.8 degrees C decreased hatch
      of fertile eggs, but had little effect on chick quality or posthatch performance.

PMID- 23873564
TI  - Neurotensin and cholecystokinin contract gallbladder circular muscle in chickens.
AB  - The contractile effects of neurotensin (NT) and cholecystokinin octapeptide (CCK
      8) on isolated circular smooth muscle strips of chicken gallbladder were
      investigated. The NT (0.25-300 nM) produced concentration-dependent contractions
      on smooth muscle with an EC50 of 8.5 nM (95% confidence limits = 5.3-13.6 nM). In
      comparison, CCK-8 produced concentration-dependent contractions with an EC50 of
      13 nM (95% confidence limits of 9-20 nM). There were no statistical differences
      in contractile responses when comparing NT and CCK-8 at equimolar concentrations.
      The NT appears to act directly on smooth muscle tissue in the chicken; the
      contractile responses were not blocked by 10 uM atropine or tetrodotoxin. A
      portion of the activity is mediated by extracellular calcium as 100 nM nifedipine
      inhibited 30% of peptide-induced muscle tension. The NT receptor (NTR) type 1
      antagonist SR 48692 (0.1 uM) did not significantly reduce NT potency. The
      contractile effects of CCK-8 remained unaltered in tissues pretreated with
      atropine, TTX, or nifedipine. The CCK-A antagonist lorglumide, at a concentration
      of 1 uM, reduced the contractile potency of CCK-8 by one-half. Avian receptors
      for NT and CCK may differ pharmacologically from their mammalian counterparts,
      but their contractile actions on the gallbladder resulting in increased biliary
      output by flow are further evidence of their role in the postprandial regulation
      of lipid digestion in chickens. 

PMID- 23873565
TI  - The effect of nutritional status on myogenic satellite cell proliferation and
      differentiation.
AB  - Early posthatch satellite cell (SC) mitotic activity is a critical component of
      muscle development and growth. Satellite cells are stem cells that can be induced
      by nutrition to follow other cellular developmental pathways. The objective of
      the current study was to determine the effect of restricting protein synthesis on
      the proliferation and differentiation of SC, using variable concentrations of Met
      and Cys to modulate protein synthesis. Broiler pectoralis major SC were cultured
      and treated with 1 of 6 different Met/Cys concentrations: 60/192, 30/96
      (control), 7.5/24, 3/9.6, 1/3.2, or 0/0 mg/L. The effect of Met/Cys concentration
      on SC proliferation and differentiation was measured, and myonuclear accretion
      was measured by counting the number of nuclei per myotube during differentiation.
      The 30/96 mg/L Met/Cys treatment resulted in the highest rate of proliferation
      compared with all other treatments by 72 h of proliferation (P < 0.05).
      Differentiation was measured with Met/Cys treatments only during proliferation
      and the cultures receiving normal differentiation medium (R/N), normal
      proliferation medium and differentiation medium with variable Met/Cys (N/R), or
      both proliferation and differentiation receiving variable Met/Cys treatments
      (R/R). Differentiation responded in a dose-dependent manner to Met/Cys
      concentration under all 3 of these treatment regimens, with a degree of recovery
      in the R/N regimen cells following reinstatement of the control medium.
      Reductions in both proliferation and differentiation were more pronounced as
      Met/Cys concentrations were further reduced, whereas increased differentiation
      was observed under the increased Met/Cys concentration treatment when applied
      during differentiation in the N/R and R/R regimens. The number of nuclei per
      myotube was significantly decreased in the severely Met/Cys restricted treatments
      (P < 0.05). These data demonstrate the sensitivity of pectoralis major SC to
      nutritional availability and the importance of optimal nutrition during both
      proliferation and differentiation for maximizing SC activity, which will affect
      subsequent muscle mass accretion. 

PMID- 23873566
TI  - Impact of 6 different intestinal bacteria on broiler breeder sperm motility in
      vitro.
AB  - Male fertility is often evaluated by measuring sperm parameters, including
      concentration, viability, and motility. This is important because after
      copulation occurs, sperm must overcome many barriers in the female reproductive
      tract to fertilize the ovum. In mammalian species, sperm have been shown to have
      reduced motility when bacteria are present. In male broiler breeders, bacteria
      have been associated with spermatozoa, but their effect on motility has not been
      investigated. The sperm quality index is a modern rapid method of evaluating
      avian sperm motility. Therefore, the objective of this study was to use the sperm
      quality index to determine if broiler breeder sperm motility is reduced when
      semen is exposed to various bacteria. In this experiment, semen was collected
      from 20 broiler breeders to obtain a pooled neat semen sample. Six different
      intestinal bacteria, Salmonella enterica, Escherichia coli, Campylobacter jejuni,
      Clostridium bifermentans, Lactobacillus acidophilus, and Bifidobacterium animalis
      were cultured overnight. For each bacterium, 50 uL of semen was diluted in 450 uL
      of saline, sterile broth, or the overnight culture, creating 3 treatments. The
      experiment was repeated twice. In each treatment, 3 replicates were evaluated at
      0 and 10 min postinoculation, creating a completely randomized design with a
      split plot over time. Also, the pH was measured for each treatment at 0 and 10
      min. The results indicated that all broths containing bacteria immediately
      reduced broiler breeder sperm motility when compared with the controls (P <
      0.0001), but broths containing Bifidobacterium or Lactobacillus virtually made
      sperm immotile. Although broth containing Salmonella, Campylobacter, and
      Bifidobacterium immediately reduced sperm motility, the reduction did not change
      over time. Broths containing E. coli, Clostridium, and Lactobacillus reduced
      sperm motility immediately, but over time motility continued to decrease.
      However, pH was increased when semen was exposed to the E. coli and Campylobacter
      treatment, but when semen was exposed to Bifidobacterium and Lactobacillus
      treatments, pH was reduced. In conclusion, the results indicate that bacteria can
      reduce broiler breeder sperm motility upon exposure. 

PMID- 23873567
TI  - The effect of treating method of pithed pheasant on the content of biogenic
      amines in the meat during the course of storage.
AB  - The study monitored the effect of various methods of treating pheasant carcasses
      after killing on the hygienic quality of the venison. Pithed pheasants treated by
      evisceration (n = 60), drawing (n = 60), or left untreated (n = 60) were stored
      for a period of 21 d at temperatures of 0, 7, and 15 degrees C. For determination
      of biogenic amines, samples of breast and thigh muscles were taken on d 1, 7, 14,
      and 21 after killing of the pheasants. Biogenic amines were separated by reverse
      phase liquid chromatography and consequently detected by tandem mass
      spectrometry. The sum of determined biogenic amine concentrations (cadaverine,
      putrescine, histamine, tyramine, tryptamine, phenylethylamine) was compared with
      the value of the index for meat of high hygienic quality (5 mg/kg). At a storage
      temperature of 0 degrees C, the sum of biogenic amine concentrations did not
      exceed the value of 5 mg/kg in either breast or thigh muscle at any time during
      the storage period in untreated and drawn pheasants, and for a period of 14 d in
      eviscerated pheasants. At a storage temperature of 7 degrees C, values lower than
      the limit of 5 mg/kg were recorded throughout the storage period in untreated
      pheasants, for a period of 14 d of storage in drawn pheasants, and for a period
      of just 7 d of storage in eviscerated birds. At the highest storage temperature
      (15 degrees C), a value of 5 mg/kg was exceeded in eviscerated and untreated
      pheasants during the course of the first week of storage, and in drawn pheasants
      after the first week of storage. Our results indicate that the most suitable
      method of treatment to ensure high hygienic quality of the meat (assessed
      according to concentration of biogenic amines) for the longest period during the
      storage of pithed pheasants is to leave the pheasant carcasses untreated,
      followed by the drawing, with the least suitable method being the widely
      recommended method of evisceration. 

PMID- 23873568
TI  - Effect of protective atmosphere on color of goose meat.
AB  - The objective of the work was to characterize the color of the of the goose
      breast meat packaged in protective atmosphere and stored in the refrigerated
      conditions. The aim was realized by determination of total heme pigment
      concentration; relative concentration of myoglobin, oxymyoglobin, and
      metmyoglobin; parameters of color L* (lightness), a* (redness), and b*
      (yellowness); and sensory evaluation of the surface color. The experimental
      material was White Koluda goose boneless breast meat with the skin from
      industrial slaughter. The following 2 protective atmospheres were used in the
      study: vacuum and modified atmosphere (MA) consisting of 80% O2 and 20% CO2. The
      muscles packed in protective atmosphere were examined on d 4, 7, 11, and 14 of
      storage. A control sample was goose breast meat stored in air and tested after 24
      h after slaughter. The total pigment concentration decreased gradually within 14
      d of storage for samples packed in 2 types of atmospheres. The increase in
      relative concentration of metmyoglobin and the decrease in oxymyoglobin relative
      concentration in total heme pigments in the meat stored in MA was noticed.
      However, in all times of storage, the relative concentration of the 3 samples of
      myoglobin forms stored in vacuum was unchanged. The color parameters (L*, a*, b*)
      did not change for 14 d of storage in the muscles packed in vacuum. One can state
      a decrease of the value of the color parameter a* as well as an increase of the
      value of the color parameter b* in the samples packed in MA. From d 11 to 14 of
      storage, goose meat packed under MA had lower sensory evaluation intensity of
      color than muscles under vacuum. The obtained data indicated that the surface
      color of goose breast meat packed in MA (consisting of 80% O2, 20% CO2) or vacuum
      packed was maintained for 11 and 14 d, respectively. 

PMID- 23873569
TI  - Quality of breast and thigh meats when broilers are fed rations containing graded
      levels of sugar syrup.
AB  - The dietary energy for broiler chicken is provided through the inclusion of
      cereal grains and vegetable oil in the ration. The cost of corn is increasing
      exponentially, whereas sugar syrup (SS) is available with reasonable cost. Sugar
      syrup can be used as a substitute for starch/grains and vegetable oil. No
      research has been reported on the effect of SS on broiler meat quality. In this
      study, Hubbard commercial broiler chicks were fed a control basal diet (corn-soy
      basal diet on an ad libitum basis) alone or with graded levels of SS. A
      completely randomized design with 3 replications (n = 3, treatments = 4 with 4
      subsamples per treatment) were used to investigate the effect of replacing part
      of the corn and oil in broiler chicken rations with graded levels of SS (5, 10,
      and 15%) on breast and thigh meat quality (proximate analysis, cooking loss,
      instrumental color, and texture and sensory properties). Rations containing up to
      15% SS had a slight effect on proximate composition of raw and cooked broiler
      breast and thigh meats. Cooking loss of thigh meat decreased significantly with
      increasing SS but increased significantly for breast meats. No significant
      differences were detected (P > 0.05) among breast or thigh meats fed rations with
      a different level of SS on all sensory properties, except that cooked thigh meat
      had a slightly harder texture. Overall, results suggest that feeding broilers
      with SS rations (up to 15%) produced high-quality breast and thigh meats with
      minimal differences. 

PMID- 23873570
TI  - Evaluation of nanoparticle-encapsulated outer membrane proteins for the control
      of Campylobacter jejuni colonization in chickens.
AB  - Numerous vaccination strategies have been evaluated to develop effective vaccines
      against Campylobacter jejuni colonization in poultry but with limited success.
      The following experiments were conducted to investigate the effect of
      biodegradable and biocompatible poly (lactide-co-glycolide) nanoparticle (NP)
      encapsulated outer membrane proteins (OMP) of C. jejuni. Chickens were vaccinated
      with different routes [subcutaneous (s/c) or oral] and doses (25, 125, or 250 ug)
      of candidate nanoparticle vaccine with appropriate control groups. Serum and
      cloacal fecal samples were taken at regular intervals of time, and the birds were
      euthanized 7 d postchallenge with C. jejuni. The results were interpreted based
      on anti-OMP immunoglobulin response in chicken and intestinal colonization of C.
      jejuni. The C. jejuni colonization in cecal and cloacal contents at 7 d
      postchallenge was below the detection limit in the s/c vaccinated groups, but the
      other groups demonstrated varying degrees of colonization. The serum IgA was
      higher in the group vaccinated s/c with OMP only compared with the rest of the
      groups. The serum- and fecal-IgY titers were consistently higher in the s/c
      vaccinated groups (with or without NP) than the rest of the groups. Elevated
      levels of OMP specific serum antibodies correlated with below the limit of
      detection levels of Campylobacter colonization in broiler chickens receiving 125
      MUg of OMP alone and the OMP+NP vaccine s/c. In conclusion, the s/c route of
      vaccination with or without NP encapsulated OMP of C. jejuni may serve as a
      candidate vaccine for control of C. jejuni colonization in chickens. 

PMID- 23873571
TI  - Screening of quinolone antibiotic residues in chicken meat and beef sold in the
      markets of Ankara, Turkey.
AB  - This study aimed to find the effects of quinolone antibiotics in chicken and beef
      used in Ankara, Turkey. Total number of 127 chicken and 104 beef meat samples
      were collected randomly from local markets for analysis. Extraction and
      determination of quinolones were made by ELISA procedure. One hundred eighteen of
      231 (51.1%) examined chicken meat and beef samples were found to contain
      quinolone antibiotic residue. Among the chicken meat and beef samples, 58 (45.7%)
      of chicken meat samples and 60 (57.7%) of beef meat samples were positive for
      quinolones, respectively. The mean levels (+/-SE) of quinolones were found to be
      30.81 +/- 0.45 ug/kg and 6.64 +/- 1.11 ug/kg in chicken and beef samples,
      respectively. This study indicated that some chicken and beef meat sold in Ankara
      contains residues of quinolone antibiotics. 

PMID- 23873572
TI  - Effect of different concentrations of acetic, citric, and propionic acid dipping
      solutions on bacterial contamination of raw chicken skin.
AB  - Bacterial contamination of raw, processed poultry may include spoilage bacteria
      and foodborne pathogens. We evaluated different combinations of organic acid (OA)
      wash solutions for their ability to reduce bacterial contamination of raw chicken
      skin and to inhibit growth of spoilage bacteria and pathogens on skin during
      refrigerated storage. In experiment 1, raw chicken skin samples were dipped into
      a suspension of either 10(8) cfu/mL of Salmonella Typhimurium, Escherichia coli
      O157:H7, or Listeria monocytogenes for 30 s and then immersed in PBS or an OA
      wash solution mixture of 0.8% citric, 0.8% acetic, and 0.8% propionic acid (at
      equal wt/vol concentrations) for an additional 30 s. In experiment 2, three
      different concentrations of the OA wash solution (0.2, 0.4, and 0.6% at equal
      wt/vol concentrations) were tested against chicken skin samples contaminated with
      Salmonella Typhimurium. Viable pathogenic bacteria on each skin sample were
      enumerated after 1 and 24 h of storage at 4 degrees C in both experiments. In
      experiment 3, skin samples were initially treated on d 1 with PBS or 2
      concentrations of the OA mixture (0.4 and 0.8%), and total aerobic bacteria were
      enumerated during a 2-wk storage period. In all experiments, significant (P <
      0.05) differences were observed when skin samples were treated with the OA wash
      solution and no spoilage organisms were recovered at any given time point,
      whereas increasing log10 numbers of spoilage organisms were recovered over time
      in PBS-treated skin samples. These results suggest that 0.2 to 0.8%
      concentrations of an equal-percentage mixture of this OA combination may reduce
      pathogens and spoilage organisms and improve food safety properties of raw
      poultry. 

PMID- 23873573
TI  - Housing system and laying hen strain impacts on egg microbiology.
AB  - Alternative hen housing is becoming more commonplace in the egg market. However,
      a complete understanding of the implications for alternative housing systems on
      egg safety has not been achieved. The current study examines the impact of
      housing Hy-Line Brown, Hy-Line Silver Brown, and Barred Plymouth Rock hens in
      conventional cage, cage-free, and free range egg production systems on shell
      microbiology. Eggs were collected at 4 sampling periods. Egg shell emulsion pools
      were formed and enumerated for total aerobic organisms, Enterobacteriaceae, and
      yeast and mold counts. Hy-Line Brown and Hy-Line Silver Brown hens produced eggs
      with significantly (P < 0.05 and 0.001, respectively) different levels of aerobic
      organisms dependent on housing system. Eggs from conventional cages had
      significantly different (P < 0.05) levels of aerobic contamination in relation to
      hen strain with Hy-Line Silver Brown having the greatest (4.57 log cfu/mL). Hy
      Line Brown and Barred Plymouth Rock hens produced eggs with significantly
      different (P < 0.01) levels of Enterobacteriaceae among housing systems with
      conventional caged eggs having the lowest level of contamination for the hen
      strains. There were no differences within each strain among housing systems for
      yeast and mold contamination. The study shows that hen strain has an effect on
      egg microbial levels for various housing systems, and egg safety should be
      considered when making hen strain selections for each housing system. 

PMID- 23873574
TI  - Growth patterns of Italian local chicken populations.
AB  - Predictions of growth are important factors that contribute to the profitability
      of an operation in poultry production. Modern commercial hybrids have a higher
      body growth in comparison with the local purebreds. However a niche market for
      meat and egg poultry production needs to be established using local purebreds to
      promote biodiversity. The aim of this study was to model the growth response of
      male and female chickens belonging to 5 local Italian populations: a commercial
      slow-growing hybrid (Berlanda, B), the Padovana pure breed [2 plumage varieties:
      silver, argentata (PA) and chamois, camosciata (PC)], and their crosses PC*B and
      PC*PA. A total of 398 one-day-old birds were reared until 180 d of age under
      indoor conditions. The linear and 3 nonlinear models (logistic, Gompertz, and
      Richards) were compared to study the growth patterns of these chicken
      populations. Significant (P < 0.01) differences were observed among the genotypes
      for several curve parameters. In males, PC*B showed the lowest age at inflection
      point, B showed the highest age and BW, whereas PA showed the highest age and the
      lowest weight. In females, the age at the inflection point did not differ among
      the groups; B showed the highest weight. All the nonlinear models gave a good fit
      of male and female data with R(2) ranging from 0.992 and 0.999, but the logistic
      equation had higher value of root mean square error than the Gompertz and the
      Richards values. Based on residual sum of squares for both sexes, the Richards
      model was better (P < 0.05) than the logistic but not superior to the Gompertz.
      The logistic equation showed an overestimation of initial BW for all the groups
      and sex. For Italian local chicken populations, the Richards model requires a
      measure of BW recorded at 90 d or after to obtain a good fit of the asymptotic
      weight. However, the Gompertz model has the advantage that it requires one less
      parameter than the Richards model. 

PMID- 23873575
TI  - Influence of eggshell ultrastructural organization on hatchability.
AB  - Eggshell quality is associated with hatchability, and ultrastructural
      organization is an important eggshell quality parameter. To the determine the
      relationship of shell ultrastructural properties with hatchability, we measured
      the effect of eggshell thickness, mammillary layer thickness, and the average
      size of mammillary cones on hatchability. Eggs with thick shells and thick
      mammillary layers had the highest incidence of hatching. As such, hatchability
      correlated positively with both eggshell thickness (r = 0.30; P < 0.05) and
      mammillary layer thickness (r = 0.28; P < 0.05). In addition, the correlation
      between the average size of mammillary cones and hatchability was not
      statistically significant. However, a significant positive correlation was
      observed between the average size of mammillary cones and mammillary layer
      thickness. It can be concluded that eggshell thickness and mammillary layer
      thickness affect hatchability. 

PMID- 23873576
TI  - The dynamic nature of the nuclear envelope: lessons from closed mitosis.
AB  - In eukaryotes, chromosomes are encased by a dynamic nuclear envelope. In contrast
      to metazoans, where the nuclear envelope disassembles during mitosis, many fungi
      including budding yeast undergo "closed mitosis," where the nuclear envelope
      remains intact throughout the cell cycle. Consequently, during closed mitosis the
      nuclear envelope must expand to accommodate chromosome segregation to the two
      daughter cells. A recent study by Witkin et al. in budding yeast showed that if
      progression through mitosis is delayed, for example due to checkpoint activation,
      the nuclear envelope continues to expand despite the block to chromosome
      segregation. Moreover, this expansion occurs at a specific region of the nuclear
      envelope- adjacent to the nucleolus- forming an extension referred to as a
      "flare." These observations raise questions regarding the regulation of nuclear
      envelope expansion both in budding yeast and in higher eukaryotes, the mechanisms
      confining mitotic nuclear envelope expansion to a particular region and the
      possible consequences of failing to regulate nuclear envelope expansion during
      the cell cycle. 

PMID- 23873578
TI  - Six weeks of voluntary exercise don't protect C57BL/6 mice against neurotoxicity
      of MPTP and MPP(+).
AB  - Exercise improves the central nervous system (CNS) functions and is widely
      recommended for neurological patients with, e.g., Alzheimer's and Parkinson's
      disease (PD). However, exercise-induced neuroprotection is an open discussion.
      Here, the intranasal administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP, 65 mg/kg) caused death of dopaminergic neurons in the
      substantia nigra pars compacta and depletion of dopamine in the striatum of
      C57BL/6 mice. 1-Methyl-4-phenylpyridinium, the active metabolite of MPTP, also
      inhibited complex-I activity of mitochondria isolated from the CNS of mice.
      However, 6 weeks of exercise on voluntary running wheels did not protect against
      nigrostriatal neurodegeneration or mitochondrial inhibition, suggesting that
      benefits of exercise for PD may not be associated with neuroprotection. The
      literature presents other candidates, such as neurotrophins or increased
      antioxidant defenses. 

PMID- 23873577
TI  - Foraging activity is reduced in a mouse model of depression.
AB  - Depression interferes with the human ability to make decisions. Multiple criteria
      have been adopted for the diagnosis of depression in humans, but no clear
      indicators are available in animal models to reflect the depressive mood,
      involving higher cognitive functions. The act of foraging is a species-specific
      behaviour which is believed to involve the decision-making and higher cognitive
      functions. We previously established a method to detect the foraging behaviour of
      rodents, in which our results demonstrated that NMDA and dopamine receptors were
      involved. Conversely, increased NMDA receptors and reduced dopamine have been
      reported in depression model rodents. However, we hypothesise that foraging
      activities may also be impaired in depression. To test the theory, we
      successfully established a mouse model of depression using the chronic
      unpredictable mild stress (CUMS) paradigm. Most interestingly, the food foraging
      activity of mice after CUMS was significantly reduced. In addition, the treatment
      of anti-depressant fluoxetine reversed most depressive symptoms and reduced glial
      fibrillary associated protein (GFAP) expression in the hippocampus, but was less
      effective in the reduction of foraging activities. However, clozapine reversed
      all symptoms of CUMS-exposed mice including reduction of GFAP expression in the
      hippocampus and impaired foraging activity. Our findings of GFAP expression as a
      marker to validate the CUMS protocol provide further validation of our
      hypothesis, that the reduced food foraging is probably a new behavioural finding
      of depression in which the serotoninergic system could not be singly involved.
      Our study suggests that NMDA receptors, serotoninergic and dopaminergic systems
      are differentially involved in these food foraging behaviours. Our data suggest
      that the foraging test in rodents can be a useful tool to assess the ability of
      decision-making in depression. 

PMID- 23873579
TI  - Five-year clinical follow-up of a randomized comparison of a polymer-free
      sirolimus-eluting stent versus a polymer-based paclitaxel-eluting stent in
      patients with diabetes mellitus (LIPSIA Yukon trial).
AB  - OBJECTIVES: The long-term performance of polymer-free stent systems in patients
      with diabetes mellitus has not been investigated extensively. This study reports
      long-term results of the LIPSIA Yukon trial which compared the polymer-free
      sirolimus-eluting Yukon Choice stent with the polymer-based paclitaxel-eluting
      Taxus Liberte stent in this subpopulation. At 9 months, the Yukon Choice stent
      failed to show non-inferiority in terms of the primary end point late lumen loss,
      while no significant difference in clinical outcome was detected. METHODS AND
      RESULTS: The LIPSIA Yukon trial randomized 240 patients with diabetes mellitus to
      a polymer-free sirolimus eluting stent (Yukon Choice, Translumina) versus a
      polymer-based paclitaxel-eluting stent (Taxus Liberte, Boston Scientific).
      Clinical follow-up was conducted with a standardized telephone follow-up and all
      events were centrally adjudicated. Follow-up was available for 98.3% of patients
      after a median of 5.0 years. The incidence of all-cause death (16.9% versus
      14.0%, P = 0.67), respectively definite or presumed cardiovascular death (7.6%
      versus 8.8%, P = 0.94) were similar in the Yukon Choice and the Taxus Liberte
      group. There were no significant differences in the rates of myocardial
      infarction (9.3% versus 7.9%, P = 0.88), definite stent thrombosis (0.8% versus
      0.9%, P = 1.0), target lesion revascularization (15.3% versus 15.8%, P = 1.0),
      target vessel revascularization (18.6% versus 23.7%, P = 0.44), non-target vessel
      revascularization (18.6% versus 26.3%, P = 0.21), and stroke (3.4% versus 4.4%, P
      = 0.96) between patients assigned to the Yukon Choice and the Taxus Liberte
      stent. CONCLUSION: At 5 years of follow-up, clinical outcome was similar between
      the polymer-free sirolimus-eluting Yukon Choice stent and the polymer-based
      paclitaxel-eluting Taxus Liberte stent.

PMID- 23873580
TI  - Patient inertia and the status quo bias: when an inferior option is preferred.
AB  - Medical noncompliance is a major public-health problem. One potential source of
      this noncompliance is patient inertia. It has been hypothesized that one cause of
      patient inertia might be the status quo bias-which is the tendency to select the
      default choice among a set of options. To test this hypothesis, we created a
      laboratory analogue of the decision context that frequently occurs in situations
      involving patient inertia, and we examined whether participants would stay with a
      default option even when it was clearly inferior to other available options.
      Specifically, in Studies 1 and 2, participants were given the option to reduce
      their anxiety while waiting for an electric shock. When doing nothing was the
      status quo option, participants frequently did not select the option that would
      reduce their anxiety. In Study 3, we demonstrated a simple way to overcome status
      quo bias in a context relevant to patient inertia. 

PMID- 23873581
TI  - Bisabololoxide A, one of the constituents in German chamomile extract, attenuates
      cell death induced by calcium overload.
AB  - Bisabololoxide A (BSBO), main constituents in German chamomile extract, is
      responsible for antipruritic effect. In previous study, the incubation with 30
      100 MUM BSBO for 24 h exerted cytotoxic and proapoptotic effects on rat
      thymocytes. To further characterize BSBO cytotoxicity, the effect on the cells
      suffering from calcium overload by calcium ionophore A23187 was examined. A23187
      induced Ca(2+) -dependent cell death. Contrary to our expectation, 1-10 MUM BSBO
      inhibited A23187-induced increase in cell lethality of rat thymocytes. BSBO
      attenuated A23187-induced increases in populations of shrunken living cells,
      phosphatidylserine-exposed living cells, and dead cells, without affecting the
      increase in intracellular Ca(2+) concentration and the Ca(2+) -dependent
      hyperpolarization. The effect of BSBO on A23187-treated cells may be unique
      because the activation of Ca(2+) -dependent K(+) channels is required for cell
      shrinkage, externalization of phosphatidylserine, and cell death in some cells.
      The cell death induced by A23187 was not inhibited by Z-VAD-FMK, a pan-inhibitor
      of caspases. Thus, the cell death may be a necrosis with some features observed
      during an early stage of apoptosis. These results suggest that BSBO at low
      micromolar concentrations is cytoprotective against calcium overload.

PMID- 23873582
TI  - Homozygosity for the V37I GJB2 mutation in fifteen probands with mild to moderate
      sensorineural hearing impairment: further confirmation of pathogenicity and
      haplotype analysis in Asian populations.
AB  - Hearing impairment affects 1 in 650 newborns, making it the most common
      congenital sensory impairment. Autosomal recessive nonsyndromic sensorineural
      hearing impairment (ARNSHI) comprises 80% of familial hearing impairment cases.
      Mutations in GJB2 account for a significant number of ARNSHI (and up to 50% of
      documented recessive (e.g., more than 1 affected sibling) hearing impairment in
      some populations). Mutations in the GJB2 gene are amongst the most common causes
      of hearing impairment in populations of various ethnic backgrounds. Two mutations
      of this gene, 35delG and 167delT, account for the majority of reported mutations
      in Caucasian populations, especially those of Mediterranean and Ashkenazi Jewish
      background. The 235delC mutation is most prevalent in East Asian populations.
      Some mutations are of less well-characterized significance. The V37I missense
      mutation, common in Asian populations, was initially described as a polymorphism
      and later as a potentially pathogenic mutation. We report here on 15 unrelated
      individuals with ARNSHI and homozygosity for the V37I GJB2 missense mutation.
      Nine individuals are of Chinese ancestry, two are of unspecified Asian descent,
      one is of Japanese descent, one individual is of Vietnamese ancestry, one of
      Philippine background and one of Italian and Cuban/Caucasian background.
      Homozygosity for the V37I GJB2 mutation may be a more common pathogenic missense
      mutation in Asian populations, resulting in mild to moderate sensorineural
      hearing impairment. We report a presumed haplotype block specific to East Asian
      individuals with the V37I mutation encompassing the GJB2 gene that may account
      for the high prevalence in East Asian populations.

PMID- 23873583
TI  - Hepatitis C genotype 1 virus with low viral load and rapid virologic response to
      peginterferon/ribavirin obviates a protease inhibitor.
AB  - The new standard of care for treatment-naive patients with hepatitis C virus
      (HCV) genotype 1 includes triple therapy with peginterferon, ribavirin, and a
      protease inhibitor. However, patients who achieve a rapid virologic response
      after 4 weeks of peginterferon and ribavirin therapy are likely to achieve a
      sustained virologic response (SVR), and we hypothesized that protease inhibitor
      therapy may be unnecessary in these patients. Treatment-naive, noncirrhosis
      patients infected with genotype-1 HCV and a low viral load at baseline were
      considered for inclusion (n = 233). After 4 weeks of lead-in therapy with
      peginterferon alpha-2b and ribavirin, 101 patients (48%) had a rapid virologic
      response (defined as undetectable levels of hepatitis C virus RNA at 4 weeks) and
      were eligible to participate. Patients were randomized 1:1 to 20 weeks of
      additional therapy with peginterferon alpha-2b and ribavirin (double therapy) or
      to 24 weeks of peginterferon alpha-2b, ribavirin, and boceprevir (triple
      therapy). There was no significant difference in rates of SVR-12 in patients
      treated with double versus triple therapy. This similarity persisted regardless
      of viral subtype (genotype 1a or 1b), interleukin (IL)-28b genotype (CC or non
      CC), or ethnicity (African American versus non-Hispanic white). CONCLUSION:
      Protease inhibitor therapy could be obviated in genotype 1-infected treatment
      naive patients with low viral load at baseline who achieve undetectable viremia
      after 4 weeks of peginterferon/ribavirin.

PMID- 23873584
TI  - Morphological and ultrastructural characterization of ionoregulatory cells in the
      teleost Oreochromis niloticus following salinity challenge combining
      complementary confocal scanning laser microscopy and transmission electron
      microscopy using a novel prefixation immunogold labeling technique.
AB  - Aspects of ionoregulatory or mitochondria-rich cell (MRC) differentiation and
      adaptation in Nile tilapia yolk-sac larvae following transfer from freshwater to
      elevated salinities, that is, 12.5 and 20 ppt are described. Investigations using
      immunohistochemistry on whole-mount Nile tilapia larvae using anti- Na+/K+-ATPase
      as a primary antibody and FluoronanogoldTM (Nanoprobes) as a secondary
      immunoprobe allowed fluorescent labeling with the high resolution of confocal
      scanning laser microscopy combined with the detection of immunolabeled target
      molecules at an ultrastructural level using transmission electron microscopy
      (TEM). It reports, for the first time, various developmental stages of MRCs
      within the epithelial layer of the tail of yolk-sac larvae, corresponding to
      immature, developing, and mature MRCs, identifiable by their own characteristic
      ultrastructure and form. Following transfer to hyperosmotic salinities the
      density of immunogold particles and well as the intricacy of the tubular system
      appeared to increase. In addition, complementary confocal scanning laser
      microscopy allowed identification of immunopositive ramifying extensions that
      appeared to emanate from the basolateral portion of the cell that appeared to be
      correlated with the localization of subsurface tubular areas displaying
      immunogold labeled Na+/K+-ATPase. This integrated approach describes a reliable
      and repeatable prefixation immunogold labeling technique allowing precise
      visualization of NaK within target cells combined with a 3D imaging that offers
      valuable insights into MRC dynamics at an ultrastructural level.

PMID- 23873585
TI  - Clinical issues and outcomes in adults following repair of tetralogy of fallot.
AB  - OPINION STATEMENT: Advances in diagnosis, perioperative and surgical management
      of neonates born with Tetralogy of Fallot (TOF) have meant that affected
      individuals can now expect to survive to adulthood. However, this success is
      counterbalanced by the development of late morbidity in adulthood affecting
      survival and functional capacity. This review article addresses some of the major
      sequelae of TOF repair and discusses the contemporary approaches to reduce
      morbidity and mortality in this population.

PMID- 23873586
TI  - Effect of different bone marrow stimulation techniques (BSTs) on MSCs
      mobilization.
AB  - The therapeutic effect of bone marrow stimulation techniques (BSTs) is mainly
      attributed to the role of mesenchymal stem cells (MSCs) from the bone marrow.
      However, no studies have directly shown the amount of MSCs drained by BSTs. This
      study hypothesized that differences in the opening of subchondral bone affect the
      number of MSCs drained from the bone marrow. We purposed that as the exposed area
      and hole size of BSTs vary, the number of MSCs drained out was measured. Three
      groups of different BSTs were designed that have variations in the sizes of total
      exposed area and individual holes. Three different BSTs using a curette, 1.5- and
      0.8-mm awls were carried out on the full-thickness femoral cartilage defect of
      young rabbits. After BST, the number of MSCs in the blood clot was measured by
      CFU-Fs assay. As the size of the total exposed area increased, so did the number
      of MSCs obtained. The number of MSCs drained from bone marrow may vary depending
      on different BSTs and this could affect therapeutic efficacy of cartilage defect.
      As current microfracture (MF) method cannot drain the most MSCs clinically, more
      improved surgery technique is needed.

PMID- 23873587
TI  - Probing columnar discotic liquid crystals by EPR spectroscopy with a rigid-core
      nitroxide spin probe.

PMID- 23873588
TI  - Can conventional bases and unsaturated hydrocarbons be converted into gas-phase
      superacids that are stronger than most of the known oxyacids? The role of
      beryllium bonds.
AB  - The association of BeX2 (X: H, F, Cl) derivatives with azoles leads to a dramatic
      increase of their intrinsic acidity. Hence, whereas 1H-tetrazole can be
      considered as a typical N base in the gas phase, the complex 1H-tetrazole-BeCl2
      is predicted to be, through the use of high-level G4 ab initio calculations, a
      nitrogen acid stronger than perchloric acid. This acidity enhancement is due to a
      more favorable stabilization of the deprotonated species after the beryllium bond
      is formed, because the deprotonated anion is a much better electron donor than
      the neutral species. Consequently, this is a general phenomenon that should be
      observed for any Lewis base, including those in which the basic site is a hydroxy
      group, an amino group, a carbonyl group, an aromatic N atom, a second-row atom,
      or the pi system of unsaturated hydrocarbons. The consequence is that typical
      bases like aniline or formamide lead to BeX2 complexes that are stronger acids
      than phosphoric or chloric acids. Similarly, water, methanol, and SH2 become
      stronger acids than sulfuric acid, pyridine becomes a C acid almost as strong as
      acetic acid, and unsaturated hydrocarbons such as ethylene and acetylene become
      acids as strong as nitric and sulfuric acids, respectively. 

PMID- 23873589
TI  - The impact of anti-inflammatory cytokines provoked by CD163 positive macrophages
      on ventricular functional recovery after myocardial infarction.
AB  - Present study aimed to investigate the impact of anti-inflammatory cytokines
      provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV)
      functional recovery after successful reperfusion in patients with acute
      myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque
      destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage
      scavenger receptor. This process provokes secretion of anti-inflammatory
      atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first
      AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary
      intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was
      determined by echocardiography before PCI and 6 months after PCI. %CD163 was
      defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the
      ratio of positively stained areas per total tissue. Patients were divided into
      two groups depending on the amount of CD163 (+)-cells: CD163 > 10 % (CD163high, n
      = 20) and CD163 <= 10 % (CD163low, n = 20). CD163high group had significantly
      higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was
      significantly lower in CD163high group. In subgroups with the final TIMI-3 flow
      (CD163high-Reflow, n = 15 and CD163low-Reflow, n = 20), the time to reperfusion,
      infarct size, LV dimensions and fractional shortening (%FS) before PCI were
      similar. Significant correlation was observed between %IL10 and changes in LV
      dimensions (diastole, r = -0.49, P = 0.01; systole, r = -0.65, P < 0.01) or %FS
      (r = 0.51, P < 0.01) at 6 months after PCI. Plaque with CD163(+)-macrophages
      could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance
      the anti-inflammatory cytokine expression that aids in ventricular functional
      recovery if distal flow can be achieved by successful reperfusion. 

PMID- 23873590
TI  - A strategy for screening and identifying mycotoxins in herbal medicine using
      ultra-performance liquid chromatography with tandem quadrupole time-of-flight
      mass spectrometry.
AB  - The objective of this study was to develop an effective strategy for screening
      and identifying mycotoxins in herbal medicine (HM). Here, Imperatae Rhizoma, a
      commonly used Chinese herb, was selected as a model HM. A crude drug contaminated
      with fungi was analyzed by comparing with uncontaminated ones. Ultra-performance
      LC coupled to tandem quadrupole TOF-MS (UPLC-Q-TOF-MS) with collision energy
      function was applied to analyze different samples from Imperatae Rhizoma. Then,
      MarkerLynx(TM) software was employed to screen the excess components in analytes,
      compared with control samples, and those selected markers were likely to be the
      metabolites of fungi. Furthermore, each of the accurate masses of the markers
      obtained from MarkerLynx(TM) was then searched in a mycotoxins/fungal metabolites
      database established in advance. The molecular formulas with relative mass error
      between the measured and theoretical mass within 5 ppm were chosen and then
      applied to MassFragment(TM) analysis for further confirmation of their
      structures. With the use of this approach, five mycotoxins that have never been
      reported in HM were identified in contaminated Imperatae Rhizoma. The results
      demonstrate the potential of UPLC-Q-TOF-MS coupled with the MarkerLynx(TM)
      software and MassFragment(TM) tool as an efficient and convenient method to
      screen and identify mycotoxins in herbal materials and aid in the quality control
      of HM. 

PMID- 23873591
TI  - Insights on Na(+) binding and conformational dynamics in multidrug and toxic
      compound extrusion transporter NorM.
AB  - MATE (multidrug and toxic compound extrusion) transporter proteins mediate
      metabolite transport in plants and multidrug resistance in bacteria and mammals.
      MATE transporter NorM from Vibrio cholerae is an antiporter that is driven by Na+
      gradient to extrude the substrates. To understand the molecular mechanism of Na+
      substrate exchange, molecular dynamics simulation was performed to study
      conformational changes of both wild-type and mutant NorM with and without cation
      bindings. Our results show that NorM is able to bind two Na(+) ions
      simultaneously, one to each of the carboxylic groups of E255 and D371 in the
      binding pocket. Furthermore, this di-Na(+) binding state is likely more efficient
      for conformational changes of NorM_VC toward the inward-facing conformation than
      single-Na(+) binding state. The observation of two Na(+) binding sites of NorM_VC
      is consistent with the previous study that two sites for ion binding (denoted as
      Na1/Na2 sites) are found in the transporter LeuT and BetP, another two secondary
      transporters. Taken together, our findings shed light on the structure
      rearrangements of NorM on Na(+) binding and enrich our knowledge of the transport
      mechanism of secondary transporters.

PMID- 23873592
TI  - In vitro tools for evaluating novel dosage forms of poorly soluble, weakly basic
      drugs: case example ketoconazole.
AB  - The aim of the present series of experiments was to compare various in vitro
      tools including evaluation of formulations influence on solubility, various
      dissolution tests, and an updated, miniaturized transfer model to forecast the
      behavior of novel formulations of the poorly soluble, weakly basic model compound
      ketoconazole (KETO) after oral administration. A binary complex with
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a ternary formulation with HP
      beta-CD and Soluplus(r) were evaluated and their solubility, dissolution, and
      transfer behavior was compared with that of the pure drug. Binary and ternary
      formulations could significantly improve (p < 0.05) KETO solubility in all test
      media. Dissolution in media simulating the fasted stomach and the fed small
      intestine was almost complete for the pure drug and both complex formulations. By
      contrast, in pH 6.5 FaSSIF, dissolution of the pure drug was less than 10%. Both
      formulations resulted in significantly higher KETO release (p < 0.05) in this
      test medium (32%/95% release from the binary/ternary formulation). In the
      transfer experiments, the ternary complex showed the best performance with
      respect to stabilizing a supersaturated solution and inhibiting precipitation of
      KETO. Overall, the miniaturized transfer model appeared to be the best single
      tool for rank-ordering formulations.

PMID- 23873593
TI  - Meta-analysis for diagnostic accuracy studies: a new statistical model using beta
      binomial distributions and bivariate copulas.
AB  - There are still challenges when meta-analyzing data from studies on diagnostic
      accuracy. This is mainly due to the bivariate nature of the response where
      information on sensitivity and specificity must be summarized while accounting
      for their correlation within a single trial. In this paper, we propose a new
      statistical model for the meta-analysis for diagnostic accuracy studies. This
      model uses beta-binomial distributions for the marginal numbers of true positives
      and true negatives and links these margins by a bivariate copula distribution.
      The new model comes with all the features of the current standard model, a
      bivariate logistic regression model with random effects, but has the additional
      advantages of a closed likelihood function and a larger flexibility for the
      correlation structure of sensitivity and specificity. In a simulation study,
      which compares three copula models and two implementations of the standard model,
      the Plackett and the Gauss copula do rarely perform worse but frequently better
      than the standard model. We use an example from a meta-analysis to judge the
      diagnostic accuracy of telomerase (a urinary tumor marker) for the diagnosis of
      primary bladder cancer for illustration.

PMID- 23873594
TI  - Evaluation of corticosterone and IL-1beta, IL-6, IL-10 and TNF-alpha expression
      after 670-nm laser photobiomodulation in rats.
AB  - The literature has shown that low-level laser therapy accelerates the repair of
      cutaneous wounds. However, there is a scarcity of scientific studies that
      characterise the possible systemic interference of laser photobiomodulation. The
      aim of this research was to quantitatively evaluate blood corticosterone levels
      and tissue cytokine expression in cutaneous wounds of rats treated with low-level
      laser therapy (semiconductor diode AsGaAl, continuous emission, 9 mW, 670 nm,
      0.031 W/cm(2), beam with an output area of 0.28 cm(2)) and normal controls. A
      total of 36 male Wistar rats were used and randomly divided into two groups of 18
      rats each. A standardised circular 6-mm-diameter wound was made in the dorsal
      skin region of each rat, and they were euthanised at 1, 6 and 12 h after
      cutaneous surgery. The blood was collected, and portions of cutaneous tissue and
      subcutaneous muscle were removed and cryopreserved. Corticosterone levels in the
      blood were measured by a radioimmunoassay technique; histological sections were
      submitted to the ELISA technique for analysis of tissue cytokine expression
      levels. At 6 h after surgery, a significant increase in corticosterone and a
      significant reduction in the levels of IL-1beta and IL-6 in tissues of irradiated
      wounds were observed when compared to controls (p < 0.05). The levels of TNF
      alpha and IL-10 expression were not significantly different between the groups at
      different time intervals. Thus, this study strongly suggests a systemic and local
      biomodulation of low-level laser therapy as indicated by the blood levels of
      corticosterone and the tissue expression of IL-1beta and IL-6, respectively. 

PMID- 23873595
TI  - Effect of different mechanical and chemical surface treatments on the repaired
      bond strength of an indirect composite resin.
AB  - This study compared the effects of two mechanical surface preparation techniques,
      air abrasion and Nd:YAG laser, with the use of two adhesive systems, self-etch
      and etch and rinse, on the repair bond strengths of an indirect composite resin.
      One hundred fifty cylindrical samples of an indirect composite resin were
      prepared and randomly divided into six groups (n = 25). In groups 1-3, the
      composite resin surfaces were respectively prepared as follows: no roughening,
      roughening by air abrasion, and roughening by Nd:YAG laser, followed by
      application of an etch-and-rinse adhesive. In groups 4-6, the preparation
      techniques were respectively the same as those in groups 1-3, followed by
      application of a self-etch adhesive. Subsequently, a direct composite resin was
      added and repair bond strengths were measured. Data were analyzed with two-way
      ANOVA and post hoc Tukey's test. Mean bond strength value was significant based
      on the preparation technique (P < 0.001), i.e., in air abrasion and Nd:YAG laser
      groups, bond strengths were significantly higher compared to no-preparation
      groups (P < 0.0005). There were significant differences in bond strength values
      between air abrasion and Nd:YAG laser groups, with significantly higher values in
      air abrasion groups (P < 0.0005). However, there were no significant differences
      in bond strength values between the adhesive systems. Furthermore, the cumulative
      effects of the adhesive system and the surface preparation technique were not
      significant. Surface preparation of the indirect composite resin with air
      abrasion and Nd:YAG laser resulted in a significant increase in the repair bond
      strength, with air abrasion being more effective. There were no significant
      differences in bond strength between the two adhesives. 

PMID- 23873596
TI  - Congenital sciatic hernia.

PMID- 23873597
TI  - Sustained-release fampridine (4-aminopyridine) in multiple sclerosis: efficacy
      and impact on motor function.
AB  - OBJECTIVE: The aim of this study was to determine the efficacy of sustained
      release fampridine (4-aminopyridine) in veterans with multiple sclerosis (MS)
      with limited ambulatory ability, and its impact on motor function in an
      outpatient setting. DESIGN: Retrospective. SETTING: Tertiary referral center
      [Veterans Affairs (VA) Medical Center]. PARTICIPANTS: Veterans; 20 MS patients
      were prescribed dalfampridine (10 mg twice daily) due to their difficulty with
      walking based on patient and caregiver report and clinician impression of change
      in the ability to ambulate based on prior 10-meter (10M) and 2-minute walk tests
      (2MWTs). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The primary outcome
      measures were mean changes in walking speed (10M walk test), walking distance
      (2MWT), and Total Functional Independence Measure (TFIM). Improvement of >20% in
      walking speed was indicated as a clinically meaningful change. RESULTS: Treatment
      with dalfampridine resulted in significant improvement in walking speed and
      endurance (p < 0.05). Walking speed increased by 33% and walking endurance by
      31%, representing clinically meaningful improvement. This change was not
      influenced by change in muscle tone. This improvement in mobility was associated
      with a clinically significant change in motor function. Adverse effects,
      including insomnia, dizziness, and headache, were experienced by five patients
      who discontinued the medication after a minimum of 4 weeks. CONCLUSION: Treatment
      with dalfampridine resulted in clinically relevant improvements in walking speed
      and endurance in MS patients with limited ambulation and helped improve their
      motor function.

PMID- 23873598
TI  - Rituximab, Ara-C, dexamethasone and oxaliplatin (R-ADOx) is effective for
      treatment of elderly patients with relapsed mantle cell lymphoma.
AB  - PURPOSE: The management of patients with mantle cell lymphoma (MCL) not eligible
      for stem cell transplantation in relapse after receiving standard approaches
      remains challenging, and the search for active and tolerable regimens is still
      warranted. PATIENTS AND METHODS: We have retrospectively analyzed activity of
      rituximab (375 mg/m(2) i.v. day 1), Ara-C (1,000 mg i.v. total twice daily on day
      2) and oxaliplatin (130 mg/m(2) i.v. day 3) (R-ADOx) in 12 patients (median age
      69 years) with relapsed MCL. RESULTS: Patients had been heavily pretreated
      (median 3 prior therapies, range 1-9) and had stage III/IV disease. Nine out of
      12 patients responded (75 %, 4 CR, 5 PR). Median progression-free survival was
      9.3 months, and overall survival has not been reached. Adverse events greater
      than grade II included anemia (17 %) and thrombocytopenia (33 %). CONCLUSION: R
      ADOx is active and well tolerated in heavily pretreated MCL patients.

PMID- 23873599
TI  - Numerical simulation of dental bone remodeling induced by implant-supported fixed
      partial denture with or without cantilever extension.
AB  - The current study aims to evaluate and compare the bony biomechanical response
      and possible long-term restorative consequences stemming from the use of two-unit
      fixed partial dentures (FPDs) with or without cantilever configuration. The
      numerical simulations of bone remodeling were performed using an adaptive strain
      energy density algorithm, which incorporates an overloading bone resorption
      process. A patient specific 3D finite element model of a maxillary bone with two
      absent central incisors was constructed on the basis of clinical computed
      tomography data. Two different implant-supported two-unit FPD models were
      developed. The simulated remodeling results were visualized by examining the
      variation of apparent bone density. Different bone responses under normal and
      overload conditions were compared quantitatively and qualitatively between the
      cantilever and non-cantilever models. The mechanical stress/strain distributions
      were also examined. Furthermore, the simulation results were compared with a
      similar clinical X-ray image of the implant site. This study revealed that bone
      resorption due to overloading was more severe in the cortical neck around the
      implant-supported cantilever FPD, as compared with the non-cantilever
      configuration, which is better for maintaining the overall health of bone tissue.
      It is expected that such simulation methodology can be helpful in improving
      longevity and reliability of future dental implants.

PMID- 23873601
TI  - Novel no-stop FLNA mutation causes multi-organ involvement in males.
AB  - Mutations in FLNA (Filamin A, OMIM 300017) cause X-linked periventricular nodular
      heterotopia (XL-PNH). XL-PNH-associated mutations are considered lethal in
      hemizygous males. However, a few males with unusual mutations (including distal
      truncating and hypomorphic missense mutations), and somatic mosaicism have been
      reported to survive past infancy. Two brothers had an atypical presentation with
      failure to thrive and distinct facial appearance including hypertelorism.
      Evaluations of these brothers and their affected cousin showed systemic
      involvement including severe intestinal malfunction, malrotation, congenital
      short bowel, PNH, pyloric stenosis, wandering spleen, patent ductus arteriosus,
      atrial septal defect, inguinal hernia, and vesicoureteral reflux. The
      unanticipated finding of PNH led to FLNA testing and subsequent identification of
      a novel no-stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). Western
      blotting and qRT-PCR of patients' fibroblasts showed diminished levels of protein
      and mRNA. This FLNA mutation, the most distal reported so far, causes in females
      classical XL-PNH, but in males an unusual, multi-organ phenotype, providing a
      unique insight into the FLNA-associated phenotypes.

PMID- 23873600
TI  - DockRank: ranking docked conformations using partner-specific sequence homology
      based protein interface prediction.
AB  - Selecting near-native conformations from the immense number of conformations
      generated by docking programs remains a major challenge in molecular docking. We
      introduce DockRank, a novel approach to scoring docked conformations based on the
      degree to which the interface residues of the docked conformation match a set of
      predicted interface residues. DockRank uses interface residues predicted by
      partner-specific sequence homology-based protein-protein interface predictor (PS
      HomPPI), which predicts the interface residues of a query protein with a specific
      interaction partner. We compared the performance of DockRank with several state
      of-the-art docking scoring functions using Success Rate (the percentage of cases
      that have at least one near-native conformation among the top m conformations)
      and Hit Rate (the percentage of near-native conformations that are included among
      the top m conformations). In cases where it is possible to obtain partner
      specific (PS) interface predictions from PS-HomPPI, DockRank consistently
      outperforms both (i) ZRank and IRAD, two state-of-the-art energy-based scoring
      functions (improving Success Rate by up to 4-fold); and (ii) Variants of DockRank
      that use predicted interface residues obtained from several protein interface
      predictors that do not take into account the binding partner in making interface
      predictions (improving success rate by up to 39-fold). The latter result
      underscores the importance of using partner-specific interface residues in
      scoring docked conformations. We show that DockRank, when used to re-rank the
      conformations returned by ClusPro, improves upon the original ClusPro rankings in
      terms of both Success Rate and Hit Rate. DockRank is available as a server at
      http://einstein.cs.iastate.edu/DockRank/.

PMID- 23873602
TI  - Effects of temperature and osmolytes on competing degradation routes for an IgG1
      antibody.
AB  - Addition of excipients is a common strategy to slow protein aggregation during
      storage. Excipient effects on the mechanism(s) and temperature (T) dependence of
      aggregation for a monoclonal antibody solution were tested using size-exclusion
      chromatography, differential scanning calorimetry (DSC), temperature scanning
      monomer loss (TSML), and laser light scattering; previous work in buffer-only
      conditions had shown non-Arrhenius behavior and implicated Fab and/or CH 3
      unfolding as a key step in aggregation. Excipients included citrate, amino acid
      salts (histidine-HCl, arginine-HCl), and polyols (mannitol and glycerol). DSC and
      TSML showed that Fab, rather than CH 3, unfolding corresponded with the onset of
      aggregation for each condition. Isothermal incubation at 56.5 degrees C, 40
      degrees C, and 2 degrees C-8 degrees C resulted in aggregation, while
      fragmentation occurred readily at only 40 degrees C. The primary effect of the
      different excipients appeared to be preferential accumulation/exclusion,
      affecting the concentrations of partially unfolded monomer key intermediates. In
      addition, aggregation rates were clearly non-Arrhenius, causing aggregation to
      dominate over fragmentation at high and low T, and making long-term stability
      predictions problematic based on commonly employed 40 degrees C conditions.
      Possible reasons for non-Arrhenius behavior include a strong T-dependence of the
      Fab unfolding enthalpy and/or a switch from Fab-mediated to Fc-mediated
      aggregation as one moves from high to low T.

PMID- 23873603
TI  - Analysis of polar peptides using a silica hydride column and high aqueous content
      mobile phases.
AB  - The retention behavior of a set of polar peptides separated on a silica hydride
      stationary phase was examined with a capillary HPLC system coupled to ESI-MS
      detection. The mobile phases consisted of formic acid or acetic
      acid/acetonitrile/water mixtures with the acetonitrile content ranging from 5 to
      80% v/v. The effects on peptide retention of these two acidic buffer additives
      and their concentrations in the mobile phase were systematically investigated.
      Strong retention of the peptides on the silica hydride phase was observed with
      relatively high-organic low-aqueous mobile phases (i.e. under aqueous normal
      phase conditions). However, when low concentrations of acetic acid were employed
      as the buffer additive, strong retention of the peptides was also observed even
      when high aqueous content mobile phases were employed. This unique feature of the
      stationary phase therefore provides an opportunity for chromatographic analysis
      of polar peptides with water-rich eluents, a feature usually not feasible with
      traditional RP sorbents, and thus under conditions more compatible with
      analytical green chemistry criteria. In addition, both isocratic and gradient
      elution procedures can be employed to optimize peptide separations with excellent
      reproducibility and resolution under these high aqueous mobile phase conditions
      with this silica hydride stationary phase. 

PMID- 23873604
TI  - Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through c-jun
      N-terminal kinase (JNK)-dependent and -independent signaling pathways.
AB  - This study examines the role of protein kinase C (PKC) and AMP-activated kinase
      (AMPK) in acetaminophen (APAP) hepatotoxicity. Treatment of primary mouse
      hepatocytes with broad-spectrum PKC inhibitors (Ro-31-8245, Go6983), protected
      against APAP cytotoxicity despite sustained c-jun-N-terminal kinase (JNK)
      activation. Broad-spectrum PKC inhibitor treatment enhanced p-AMPK levels and
      AMPK regulated survival-energy pathways including autophagy. AMPK inhibition by
      compound C or activation using an AMPK activator oppositely modulated APAP
      cytotoxicity, suggesting that p-AMPK and AMPK regulated energy survival pathways,
      particularly autophagy, play a critical role in APAP cytotoxicity. Ro-31-8245
      treatment in mice up-regulated p-AMPK levels, increased autophagy (i.e.,
      increased LC3-II formation, p62 degradation), and protected against APAP-induced
      liver injury, even in the presence of sustained JNK activation and translocation
      to mitochondria. In contrast, treatment of hepatocytes with a classical PKC
      inhibitor (Go6976) protected against APAP by inhibiting JNK activation. Knockdown
      of PKC-alpha using antisense (ASO) in mice also protected against APAP-induced
      liver injury by inhibiting JNK activation. APAP treatment resulted in PKC-alpha
      translocation to mitochondria and phosphorylation of mitochondrial PKC
      substrates. JNK 1 and 2 silencing in vivo decreased APAP-induced PKC-alpha
      translocation to mitochondria, suggesting PKC-alpha and JNK interplay in a feed
      forward mechanism to mediate APAP-induced liver injury. CONCLUSION: PKC-alpha and
      other PKC(s) regulate death (JNK) and survival (AMPK) proteins, to modulate APAP
      induced liver injury.

PMID- 23873605
TI  - The anti-obesity effects of the dietary combination of fermented red ginseng with
      levan in high fat diet mouse model.
AB  - In this study, to evaluate the anti-obesity effects of fermented red ginseng
      (FG), levan (L), and their combination (FGL), we investigated their effects on
      the weights of body, liver and white adipose tissue, lipid profiles, and
      biomarkers for insulin resistance in high fat diet (HFD)-induced obese C57BL/6J
      male mice. Furthermore, the levels of leptin in the serum were measured. FG (150
      mg/kg/d), L (100 mg/kg/d), and FGL (150 mg/kg/d of FG plus 100 mg/kg/d of L) were
      administered orally to mice daily for 11 weeks. After 11 weeks feeding, FGL
      showed significantly lower body weight and fat mass with decreasing food
      efficiency ratio than the HFD control mice. In addition, the FGL group was
      significantly lower in the levels of total cholesterol and fasting blood glucose
      and score of the homeostatic model assessment of insulin resistance. Furthermore,
      FGL decreased serum leptin levels compared to the HFD control group. Taken
      together, FGL showed a significant anti-obesity effect in HFD-induced obese mice
      and prevent insulin and leptin resistance. FGL may be potentially useful for the
      prevention of obesity.

PMID- 23873606
TI  - Radiation dose reduction using a neck detection algorithm for single spiral brain
      and cervical spine CT acquisition in the trauma setting.
AB  - Cervical spine injuries occur in 4-8 % of adults with head trauma. Dual
      acquisition technique has been traditionally used for the CT scanning of brain
      and cervical spine. The purpose of this study was to determine the efficacy of
      radiation dose reduction by using a single acquisition technique that
      incorporated both anatomical regions with a dedicated neck detection algorithm.
      Thirty trauma patients for brain and cervical spine CT were included and were
      scanned with the single acquisition technique. The radiation doses from the
      single CT acquisition technique with the neck detection algorithm, which allowed
      appropriate independent dose administration relevant to brain and cervical spine
      regions, were recorded. Comparison was made both to the doses calculated from the
      simulation of the traditional dual acquisitions with matching parameters, and to
      the doses of retrospective dual acquisition legacy technique with the same sample
      size. The mean simulated dose for the traditional dual acquisition technique was
      3.99 mSv, comparable to the average dose of 4.2 mSv from 30 previous patients who
      had CT of brain and cervical spine as dual acquisitions. The mean dose from the
      single acquisition technique was 3.35 mSv, resulting in a 16 % overall dose
      reduction. The images from the single acquisition technique were of excellent
      diagnostic quality. The new single acquisition CT technique incorporating the
      neck detection algorithm for brain and cervical spine significantly reduces the
      overall radiation dose by eliminating the unavoidable overlapping range between 2
      anatomical regions which occurs with the traditional dual acquisition technique. 

PMID- 23873607
TI  - Into the occult: strategies for preventing transfusion-transmissible infections.

PMID- 23873608
TI  - Surgery for degenerative spondylolisthesis: open versus minimally invasive
      surgery.

PMID- 23873609
TI  - Improved survival of uncemented versus cemented femoral stems in patients aged <
      70 years in a community total joint registry.
AB  - BACKGROUND: Aseptic loosening of the femoral stem remains a significant reason
      for revision in total hip arthroplasty (THA). Although stem fixation methods have
      changed over time, there is relatively little evidence supporting cemented or
      uncemented stems as more durable constructs. QUESTIONS/PURPOSES: We examined
      whether there was a difference in survival to revision between cemented and
      uncemented THA stems (1) for any reason; (2) for aseptic loosening or loosening
      related to wear/osteolysis; (3) based on patient age groupings (as a proxy for
      patient activity level); and (4) based on procedural timeframe groupings between
      cemented and uncemented stems. METHODS: A total of 6498 primary cemented and
      uncemented THAs were registered in our community total joint replacement registry
      between 1991 and 2011. Analysis was performed to compare age, sex, procedural
      timeframe, and diagnosis for both groups. Our primary outcome was revision of the
      stem component for aseptic loosening or loosening secondary to wear/osteolysis.
      Analyses were done using Wilcoxon rank sum tests, Pearson's chi-square tests,
      Kaplan Meier methods, and Cox regression. RESULTS: After adjusting for age, sex,
      primary diagnosis, and procedural timeframe as confounders, cemented femoral stem
      components were 1.63 times as likely as uncemented stems to be revised for any
      reason (p = 0.02) and 3.76 times as likely as uncemented stems to be revised for
      aseptic loosening or loosening related to wear/osteolysis (p < 0.001). When
      grouped by age, specifically in regard to revisions for aseptic loosening or
      loosening related to wear/osteolysis, uncemented stems had lower cumulative
      revision rates in patients aged < 70 years (p < 0.001) compared with cemented
      stems. There was a trend away from cemented fixation in our registry, which
      shifted from over 80% cemented stem use in 1996 to 3% in 2011. CONCLUSIONS: We
      found that uncemented stems were associated with fewer revisions for aseptic
      loosening in patients < 70 years old, but when all reasons for revision were
      considered, neither group demonstrated superior survival. With a mean followup of
      6.5 years, longer followup is needed to verify these results over time.

PMID- 23873610
TI  - Let's not abandon transfemoral intervention just yet.

PMID- 23873611
TI  - Finding novel genes by testing G * E interactions in a genome-wide association
      study.
AB  - In a genome-wide association study (GWAS), investigators typically focus their
      primary analysis on the direct (marginal) associations of each single nucleotide
      polymorphism (SNP) with the trait. Some SNPs that are truly associated with the
      trait may not be identified in this scan if they have a weak marginal effect and
      thus low power to be detected. However, these SNPs may be quite important in
      subgroups of the population defined by an environmental or personal factor, and
      may be detectable if such a factor is carefully considered in a gene-environment
      (G * E) interaction analysis. We address the question "Using a genome wide
      interaction scan (GWIS), can we find new genes that were not found in the primary
      GWAS scan?" We review commonly used approaches for conducting a GWIS in case
      control studies, and propose a new two-step screening and testing method (EDG*E)
      that is optimized to find genes with a weak marginal effect. We simulate several
      scenarios in which our two-step method provides 70-80% power to detect a disease
      locus while a marginal scan provides less than 5% power. We also provide
      simulations demonstrating that the EDG*E method outperforms other GWIS approaches
      (including case only and previously proposed two-step methods) for finding genes
      with a weak marginal effect. Application of this method to a G * Sex scan for
      childhood asthma reveals two potentially interesting SNPs that were not
      identified in the marginal-association scan. We distribute a new software program
      (G*Escan, available at http://biostats.usc.edu/software) that implements this new
      method as well as several other GWIS approaches. 

PMID- 23873612
TI  - Relative transgene expression frequencies in homozygous versus hemizygous
      transgenic mice.
AB  - We have used a simple binomial model of stochastic transgene inactivation at the
      level of the chromosome or transgene, rather than the cellular level, for the
      analysis of two mouse transgenic lines that show variegated patterns of
      expression. This predicts the percentages of cells that express one, both or
      neither alleles of the transgene in homozygotes from the observed percentages of
      cells, which express the transgene in hemizygotes. It adequately explained the
      relationship between the numbers of cells expressing the transgene in hemizygous
      and homozygous mosaic 21OH/LacZ mouse adrenals and mosaic BLG/7 mouse mammary
      glands. The binomial model also predicted that a small proportion of cells in
      mosaic mammary glands of BLG/7 homozygotes would express both BLG/7 alleles but
      published data indicated that all cells expressing the transgene showed
      monoallelic expression. Although it didn't fit all of the BLG/7 data as precisely
      as a more complex model, which used several ad hoc assumptions to explain these
      results, the simple binomial model was able to explain the relationship in
      observed transgene expression frequencies between hemizygous and homozygous
      mosaic tissues for both 21OH/LacZ and BLG/7 mice. It may prove to be a useful
      general model for analysing other transgenic animals showing mosaic transgene
      expression. 

PMID- 23873613
TI  - Expanding the genetic code for photoclick chemistry in E. coli, mammalian cells,
      and A. thaliana.

PMID- 23873614
TI  - Non-ignorable loss to follow-up: correcting mortality estimates based on
      additional outcome ascertainment.
AB  - Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In
      antiretroviral treatment (ART) programs for patients with human immunodeficiency
      virus (HIV), mortality estimates can be biased if the LTFU mechanism is non
      ignorable, that is, mortality differs between lost and retained patients. In this
      setting, routine procedures for handling missing data may lead to biased
      estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of
      the missing data mechanism is needed. This can be based on additional outcome
      ascertainment for a sample of patients LTFU, for example, through linkage to
      national registries or through survey-based methods. In this paper, we
      demonstrate how this additional information can be used to construct estimators
      based on inverse probability weights (IPW) or multiple imputation. We use
      simulations to contrast the performance of the proposed estimators with methods
      widely used in HIV cohort research for dealing with missing data. The practical
      implications of our approach are illustrated using South African ART data, which
      are partially linkable to South African national vital registration data. Our
      results demonstrate that while IPWs and proper imputation procedures can be
      easily constructed from additional outcome ascertainment to obtain valid overall
      estimates, neglecting non-ignorable LTFU can result in substantial bias. We
      believe the proposed estimators are readily applicable to a growing number of
      studies where LTFU is appreciable, but additional outcome data are available
      through linkage or surveys of patients LTFU.

PMID- 23873615
TI  - Seasonal changes in infrapopulations of Diplozoon kashmirensis Kaw, 1950
      (Monogenea: Diplozoidae) along a eutrophic gradient.
AB  - Seasonal population dynamics of the monogenean, Diplozoon kashmirensis Kaw, on
      the gills of two cyprinid fish species, Schizothorax niger Heckel and Carassius
      carassius (Linnaeus), was investigated in three limnologically distinct trophic
      habitats located along the flood plain of River Jhelum in Kashmir from June 2006
      to May 2008. The parasite infrapopulations exhibited a marked seasonal regime in
      infestation pattern as the infection indices increased to a much higher plateau
      during summer season at all the lakes, while the lows were recorded in winter.
      The heterogeneity in infection pattern indicates that water temperature is an
      important determinant of the seasonality of infrapopulations at all the
      localities. Furthermore, the results of our work clearly indicate that the
      parasite infrapopulations increased proportionally with eutrophication level and,
      as such, the highly eutrophic habitat, Anchar Lake, was significantly more
      favourable for parasite infrapopulations than the less eutrophic ones. However,
      the lakes presented no significant interlake differences in water temperature.
      Therefore, we could argue that interlake differences in the infestation pattern
      of parasite can be safely attributed to respective water quality in the lakes
      rather than water temperature. We propose that infrapopulations of the diplozoid
      studied herein do respond to differences in water quality of lakes and, thus,
      could qualify as simple and reliable indicator species in short-term comparative
      assays by lake managers. 

PMID- 23873616
TI  - Antimalarial, hematological, and antioxidant effects of methanolic extract of
      Terminalia avicennioides in Plasmodium berghei-infected mice.
AB  - Terminalia avicennioides Guill. & Perr. (Combretaceae) is used traditionally to
      treat malaria in Nigeria. To establish its efficacy, methanolic extract of T.
      avicennioides bark was investigated for antimalarial activity against Plasmodium
      berghei (NK-65) in mice. Twenty-five mice in five groups were used for this
      study. Group 1 was uninfected normal control. Twenty mice infected with P.
      berghei were grouped as untreated negative control (group 2), 5 mg/kg b.w. p.o.
      artesunate-treated positive control (group 3), and 100 and 200 mg/kg b.w. p.o. T.
      avicennioides-treated infected mice (groups 4 and 5, respectively). Four-day
      suppressive effects on P. berghei and hematological and oxidative statuses of the
      mice were assessed. Suppression of parasitemia by artesunate and methanolic
      extract of T. avicennioides (at 100 and 200 mg/kg b.w.) after 1 day of treatment
      was 10, 18, and 11% respectively; at day 5, the level of suppression was 77, 82,
      and 84% respectively. P. berghei infection decreased hemoglobin, red blood cell,
      and lymphocyte counts and increased neutrophil count; artesunate and medicinal
      plant treatment restored these parameters to normal control levels. Also,
      artesunate and medicinal plant treatment of infected mice significantly (p <
      0.05) increased serum and liver superoxide dismutase activities and significantly
      (p < 0.05) reduced serum malondialdehyde concentration compared to untreated
      infected mice. The antimalarial effect of T. avicennioides is comparable to that
      of artesunate. The restoration of oxidative and hematological statuses, to normal
      values by T. avicennioides, may provide better protection against the malaria
      severity and complications.

PMID- 23873617
TI  - Phylogenetic position of Linguatula arctica and Linguatula serrata (Pentastomida)
      as inferred from the nuclear 18S rRNA gene and the mitochondrial cytochrome c
      oxidase subunit I gene.
AB  - Genomic DNA was isolated from a Linguatula serrata female expelled from a dog
      imported to Norway from Romania and from four Linguatula arctica females
      collected from semi-domesticated reindeer from northern Norway and subjected to
      PCR amplification of the complete nuclear 18S rRNA gene and a 1,045-bp portion of
      the mitochondrial cytochrome c oxidase subunit I gene (cox1). The two species
      differed at two of 1,830 nucleotide positions (99.9% identity) of the complete
      18S rRNA gene sequences and at 102 of 1,045 nucleotide positions (90.2% identity)
      of the partial cox1 sequences. The four isolates of L. arctica showed no genetic
      variation in either gene. The new cox1 primers may facilitate the diagnosis of
      various developmental stages of L. arctica and L. serrata in their hosts. In
      separate phylogenetic analyses using the maximum likelihood method on sequence
      data from either gene, L. arctica and L. serrata clustered with members of the
      order Cephalobaenida rather than with members of the order Porocephalida, in
      which the genus Linguatula is currently placed based on morphological characters.
      The phylogenetic relationship of L. arctica, L. serrata and other pentastomids to
      other metazoan groups could not be clearly resolved, but the pentastomids did not
      seem to have a sister relationship to crustaceans of the subclass Branchiura as
      found in other studies. A more extensive taxon sampling, including molecular
      characterisation of more pentastomid taxa across different genera, seems to be
      necessary in order to estimate the true relationship of the Pentastomida to other
      metazoan groups.

PMID- 23873618
TI  - Macroparasite community of the Eurasian red squirrel (Sciurus vulgaris): poor
      species richness and diversity.
AB  - The Eurasian red squirrel (Sciurus vulgaris) is the only naturally occurring tree
      squirrel throughout its range. We aim at improving current knowledge on its
      macroparasite fauna, expecting that it will have a poor parasite diversity
      because in species that have no sympatric congeners parasite richness should be
      lower than in hosts sharing their range with several closely related species,
      where host-switching events and lateral transmission are promoted. We examined
      gastro-intestinal helminth and ectoparasite communities (excluding mites) of,
      respectively, 147 and 311 red squirrel roadkills collected in four biogeographic
      regions in Italy and France. As expected, the macroparasite fauna was poor: we
      found five species of nematodes and some unidentified cestodes, three fleas, two
      sucking lice and two hard ticks. The helminth community was dominated by a single
      species, the oxyurid Trypanoxyuris (Rodentoxyuris) sciuri (prevalence, 87%; mean
      abundance, 373 +/- 65 worms/host). Its abundance varied among seasons and
      biogeographic regions and increased with body mass in male hosts while decreased
      in females. The most prevalent ectoparasites were the flea Ceratophyllus
      (Monopsyllus) sciurorum (28%), whose presence was affected by season, and the
      generalist tick Ixodes (Ixodes) ricinus that was found only in France (34%). All
      the other helminths and arthropod species were rare, with prevalence below 10%.
      However, the first record of Strongyloides robustus, a common nematode of North
      American Eastern grey squirrels (S. carolinensis), in two red squirrels living in
      areas where this alien species co-inhabits, deserves further attention, since low
      parasite richness could result in native red squirrels being particularly
      vulnerable to parasite spillover.

PMID- 23873619
TI  - Th1 and Th2 cytokine gene expression in primary infection and vaccination against
      Fasciola gigantica in buffaloes by real-time PCR.
AB  - Th1 and Th2 cytokine gene expression in buffalo calves during primary infection
      with Fasciola gigantica as well as in response to immunization with the parasite
      recombinant fatty acid binding protein (rFABP) and recombinant glutathione S
      transferase (rGST) proteins was measured at 14th week of infection by real-time
      PCR with the double-stranded DNA-binding dye SYBR Green. Experimental animals
      were randomly distributed into FABP, GST, cocktail, challenge and healthy groups.
      Animals in groups FABP and GST were immunized with 400 MUg rFABP and rGST,
      respectively, and cocktail group with a mixture of 400 MUg each of rFABP and rGST
      in the neck and thigh muscles. All animals received three immunizations at 3-week
      interval. Calves were challenged per os with 400 viable metacercariae along with
      the unimmunized challenge control group 1 month after the last immunization.
      Expression of various cytokines in response to the immunization and parasite
      primary infection was measured by real-time PCR. Expression of IL-2 (4.5-fold)
      and IFN-gamma (3.2-fold), followed by IL-6 (1.7-fold) and IL-4 (1.6-fold), with
      downregulation of TNF-alpha and IL-10 was observed in response to F. gigantica
      infection in these animals. However, there was a sharp increase in the expression
      of the IL-4 (211.93 and 111.81-fold) and IL-6 mRNA (219.22 and 48.29-fold) to GST
      and FABP immunizations, respectively. A downregulation of the IL-1alpha, a Th1
      cytokine in response to FABP and GST immunization in these calves, was also
      observed. Overall, a mixed type of Th1 and Th2 cytokine environment was evoked to
      chronic F. gigantica infection and immunization with the above two recombinant
      proteins in buffaloes.

PMID- 23873620
TI  - A reliable and reproducible technique for DNA fingerprinting in biorepositories:
      a pilot study from BioBIM.
AB  - Standard operating procedures (SOPs) optimization for nucleic acid extraction
      from stored samples is of crucial importance in a biological repository,
      considering the large number of collected samples and their future downstream
      molecular and biological applications. However, the validity of molecular studies
      using stored specimens depends not only on the integrity of the biological
      samples, but also on the procedures that ensure the traceability of the same
      sample, certifying its uniqueness, and ensuring the identification of potential
      sample contaminations. With this aim, we have developed a rapid, reliable, low
      cost, and simple DNA fingerprinting tool for a routine use in quality control of
      biorepositories samples. The method consists of a double ALU insertion/deletion
      genotyping panel suitable for uniqueness, identification of sample
      contaminations, and gender validation. Preliminary data suggest that this easy-to
      use DNA fingerprinting protocol could routinely provide assurances of DNA
      identity and quality in a biorepository setting. 

PMID- 23873621
TI  - Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in
      males, smokers, and non-adenocarcinoma lung cancer in patients with EGFR
      mutations.
AB  - INTRODUCTION: The demographical/clinical characteristics of being Asian, having
      an adenocarcinoma, being female, and being a "never-smoker" are regarded as
      favorable predictors for epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor (TKI) efficacy in non-small cell lung cancer (NSCLC) with unknown EGFR
      gene status. In this study, we examined the effects of the supposedly unfavorable
      clinical variables in EGFR-mutant patients. METHOD: In total, 159 EGFR-mutant
      NSCLC patients' clinical features were correlated with progression-free survival
      (PFS), response rate (RR), and overall survival (OS). Multivariate analysis of
      clinical characteristics was performed using the Cox and logistic regression
      methods. RESULT: There were 90 females (56.6%), 112 never-smokers (70.4%), and
      153 patients with adenocarcinomas (96.2%). All patients were treated with EGFR
      TKI, and 52.8% received TKI in a first-line setting. The median PFS of patients
      receiving first-line TKI was similar, regardless of gender (males vs females: 9.1
      vs 9.7 months, p=0.793), smoking status (never-smokers vs smokers: 9.9 vs 9.1
      months, p=0.570), or histology (adenocarcinoma vs non-adenocarcinoma: 9.7 vs 9.2
      months, p=0.644). OS curves of first-line TKI-treated patients were also not
      associated with gender (p=0.722), smoking status (p=0.579), or histology
      (p=0.480). Similar results of PFS and OS were obtained for patients who received
      TKI beyond first-line. Multivariate analysis indicated that none of these
      clinical factors was an independent predictor of survival. CONCLUSIONS: The
      supposedly 'favorable' clinical factors of female gender, non-smoking status, and
      adenocarcinoma were not independent predictive factors for PFS or OS in this
      population of EGFR-mutant NSCLC patients.

PMID- 23873622
TI  - A new germline stop codon mutation in exon 15 of the APC gene predisposing to
      familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant disorder related to
      germline mutations of the adenomatous polyposis coli (APC) gene. It is
      characterized by the detection of numerous adenomatous polyps that, if untreated,
      develop into colorectal cancer. We studied an Italian family with FAP history and
      the related colorectal tumor sample of the proband. Sequencing analysis of blood
      samples revealed the presence of a never-reported germline mutation in the APC
      gene (exon 15): an heterozygous G deletion at position c.2126 resulting in a
      premature stop codon (p.Gly721GlufsX6) and in a truncated protein. This mutation
      was also identified in the colorectal tumor tissue, together with a second known
      pathogenic heterozygotic somatic mutation, c.4348C>T (p.Arg1450X), which
      generates a premature truncated protein. The novel identified germline mutation
      is therefore related to FAP and, in accordance with Knudson's "two hit"
      hypothesis, can be considered the first event predisposing to the insurgence of
      colorectal cancer in these patients. The somatic hit inactivating the second
      allele of the APC gene is located in the mutation cluster region of the gene;
      this is not a random event since it depends on the position of the germline
      mutation. The inactivation of APC generates the neoplastic growth advantage to
      the cell. 

PMID- 23873623
TI  - Computational analysis optimizes the flow cytometric evaluation for lymphoma.
AB  - Background: Although many clinical laboratories are adopting higher color flow
      cytometric assays, the approach to optimizing panel design and data analysis is
      often traditional and subjective. In order to address the question "What is the
      best flow cytometric strategy to reliably distinguish germinal center B-cell
      lymphoma (GC-L) from lymphoid hyperplasia (GC-H)?" we applied a computational
      tool that identifies target populations correlated with a desired outcome, in
      this case diagnosis. Design: Cases of GC-H and GC-L with a germinal center
      phenotype, evaluated by flow cytometric immunophenotyping using CD45, CD20,
      kappa, lambda, CD19, CD5, CD10, CD38, were analyzed with flowType and RchyOptimyx
      to construct cellular hierarchies that best distinguished the two diagnostic
      groups. Results: The population CD5-CD19+CD10+CD38- had the highest predictive
      power. Manual reanalysis confirmed significantly higher CD10+/CD38-B-cells in GC
      L (median 12.44%, range 0.74 - 63.29, n=52) than GC-H (median 0.24%, 0.03 - 4.49,
      n=48, p=0.0001), but was not entirely specific. Difficulties encountered using
      this computational approach included the presence of CD10+ granulocytes,
      continuously variable B-cell expression of CD38, more variable intensity antigen
      staining in GC-L and inability to assess the contribution of light chain
      restriction. Conclusion: Computational analysis with construction of cellular
      hierarchies related to diagnosis helped guide manual analysis of high dimensional
      flow cytometric data. This approach highlighted the diagnostic utility of CD38
      expression in the evaluation of B-cells with a CD10+ GC phenotype. In contrast to
      computational analysis of non-neoplastic cell populations, evaluation of
      neoplastic cells must be able to take into consideration increased variability in
      antigen expression. (c) 2013 Clinical Cytometry Society.

PMID- 23873624
TI  - SIRPIDS: an unusual EEG pattern in a critically ill patient.

PMID- 23873625
TI  - Diazadithia[7]helicenes: Synthetic Exploration, Solid-State Structure, and
      Properties.
AB  - Diazadithia[7]helicenes were synthesized from the readily available building
      block ethyl 7-chloro-8-formylthieno[3,2-f]quinoline-2-carboxylate by a Wittig
      reaction-photocyclization strategy. The helicene core was functionalized by
      nucleophilic aromatic substitution with a variety of nucleophiles (e.g., O-, N-,
      and C-centered) and palladium-catalyzed reactions such as Suzuki coupling and
      Buchwald-Hartwig amination. Racemization studies confirmed that the enantiopure
      forms of these [7]helicenes are conformationally stable compared to their lower
      analogues. The solid-state structures of the novel diazadithia[7]helicenes were
      determined by single-crystal X-ray diffraction. The crystal structures of these
      azathia[7]helicenes show columnar stacking in antiparallel fashion. The HOMO-LUMO
      gaps of the new compounds were determined on the basis of electrochemical and
      optical measurements. 

PMID- 23873626
TI  - Rigid-body motions of interacting proteins dominate multispecific binding of
      ubiquitin in a shape-dependent manner.
AB  - To understand the dynamic aspects of multispecificity of ubiquitin, we studied
      nine ubiquitin-ligand (partner protein) complexes by normal mode analysis based
      on an elastic network model. The coupling between ubiquitin and ligand motions
      was analyzed by decomposing it into rigid-body (external) and vibrational
      (internal) motions of each subunit. We observed that in total the external
      motions in one of the subunits largely dominated the coupling. The combination of
      external motions of ubiquitin and the ligands showed general trends of rotations
      and translations. Moreover, we observed that the rotational motions of ubiquitin
      were correlated to the ligand orientations. We also identified ubiquitin atomic
      vibrations that differentiated the orientation of the ligand molecule. We
      observed that the extents of coupling were correlated to the shapes of the
      ligands, and this trend was more pronounced when the coupling involved
      vibrational motions of the ligand. In conclusion, an intricate interplay between
      internal and external motions of ubiquitin and the ligands help understand the
      dynamics of multispecificity, which is mostly guided by the shapes of the ligands
      and the complex.

PMID- 23873627
TI  - Allergic rhinitis.

PMID- 23873628
TI  - Cell entry, efficient RNA replication, and production of infectious hepatitis C
      virus progeny in mouse liver-derived cells.
AB  - Only humans and chimpanzees are susceptible to chronic infection by hepatitis C
      virus (HCV). The restricted species tropism of HCV is determined by distinct host
      factor requirements at different steps of the viral life cycle. In addition,
      effective innate immune targeting precludes efficient propagation of HCV in
      nonhuman cells. Species-specificity of HCV host factor usage for cell entry and
      virus release has been explored. However, the reason for inefficient HCV RNA
      replication efficiency in mouse liver cells remains elusive. To address this, we
      generated novel mouse liver-derived cell lines with specific lesions in
      mitochondrial antiviral signaling protein (MAVS), interferon regulatory factor 3
      (IRF3), or Interferon-alpha/beta receptor (IFNAR) by in vivo immortalization.
      Blunted innate immune responses in these cells modestly increased HCV RNA
      replication. However, ectopic expression of liver-specific human microRNA 122
      (miR-122) further boosted RNA replication in all knockout cell lines. Remarkably,
      MAVS(-/-) miR-122 cells sustained vigorous HCV RNA replication, attaining levels
      comparable to the highly permissive human hepatoma cell line Huh-7.5. RNA
      replication was dependent on mouse cyclophilin and phosphatidylinositol-4 kinase
      III alpha (PI4KIIIalpha) and was also observed after transfection of full-length
      viral RNA. Additionally, ectopic expression of either human or mouse
      apolipoprotein E (ApoE) was sufficient to permit release of infectious particles.
      Finally, expression of human entry cofactors rendered these cells permissive to
      HCV infection, thus confirming that all steps of the HCV replication cycle can be
      reconstituted in mouse liver-derived cells. CONCLUSION: Blunted innate immunity,
      abundant miR-122, and HCV entry factor expression permits propagation of HCV in
      mouse liver-derived cell lines.

PMID- 23873629
TI  - Raman microspectroscopic discrimination of TCam-2 cultures reveals the presence
      of two sub-populations of cells.
AB  - TCam-2 cells are the main in vitro model for investigations into seminomatous
      tumors. However, despite their widespread use, questions remain regarding the
      cells' homogeneity and consequently how representative they are of seminomas. We
      assess the TCam-2 cell line using routine and novel authentication methods to
      determine its homogeneity, identify any cellular sub-populations and resolve
      whether any changes could be due to generational differentiation. TCam-2,
      embryonal carcinoma cells (2102EP) and breast cancer cell (MCF7) lines were
      assessed using qRT-PCR, immunocytochemistry, flow cytometry and short tandem
      repeat analyses. Raman maps of individual cells (minimum of 10) and single scan
      spectra from 200 cells per culture were obtained. TCam-2s displayed the
      characteristic marker gene expression pattern for seminoma, were uniform in size
      and granularity and short tandem repeat analysis showed no contamination.
      However, based only on physical parameters, flowcytometry was unable to
      differentiate between TCam-2 and 2102EPs. Raman maps of TCam-2s comprised three
      equally distributed, distinct spectral patterns displaying large intercellular
      single spectral variation. All other cells showed little variation. Principal
      component, cluster and local spectral angle analyses indicated that the TCam-2s
      contained two different types of cells, one of which comprised two subgroups and
      was similar to some 2102EP cells. Protein expression corroborated the presence of
      different cells and generational differences. The detailed characterization
      provided by the Raman spectra, augmented by the routine methods, provide
      substantiation to the long-held suspicion that TCam-2 are not homogeneous but
      comprise differing cell populations, one of which may be embryonal carcinoma in
      origin. 

PMID- 23873630
TI  - The physical stability of the recombinant tuberculosis fusion antigens h1 and
      h56.
AB  - The recombinant fusion proteins hybrid 1 [H1 (Ag85B-ESAT-6)] and hybrid 56 [H56
      (Ag85B-ESAT-6-Rv2660c)] derived from Mycobacterium tuberculosis are promising
      antigens for subunit vaccines against tuberculosis. Both antigens are early
      batches of antigens to be enrolled in human clinical trials and it is therefore
      important to characterize their conformational stability in solution as well as
      upon interaction with adjuvants. In this study, the physical stability of the two
      antigens was characterized using a number of biophysical techniques. Dynamic
      light scattering and sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      analyses demonstrated that both antigens exist as a distribution of multimeric
      states under nonstressed conditions. Their conformational stability was monitored
      as a function of pH and temperature and visualized in three-index empirical phase
      diagrams. Both antigens showed a gradual loss of secondary as well as tertiary
      structure as a function of temperature, with no cooperative transitions observed.
      Preformulation studies with the Th1-inducing cationic adjuvant CAF01 showed that
      the antigens were almost completely surface adsorbed. Upon adsorption, the
      liposome size increased; however, the physical stabilities of the bound and the
      unbound antigens were comparable. This study provides important information about
      the biophysical properties of H1 and H56 and highlights the analytical challenges
      of characterizing complex vaccine formulations.

PMID- 23873631
TI  - Framing risk: communication messages in the Australian and Swedish print media
      surrounding the 2009 H1N1 pandemic.
AB  - BACKGROUND: Australia and Sweden have similar immunisation rates. However, during
      the 2009 H1N1 pandemic the uptake of immunisation was 60% in Sweden and 18% in
      Australia. During pandemics, perceptions of risk are largely formed by media
      communication which may influence the public's response. AIM: The study aimed to
      compare the differences in how the media framed the 2009 H1N1 pandemic message
      and the associated public perceptions of risk as expressed through the uptake of
      vaccinations in Australia and Sweden. METHODS: A qualitative content analysis was
      conducted on 81 articles from the Australian and Swedish print media: 45 and 36,
      respectively. RESULTS: The risk of H1N1 was communicated similarly in Australia
      and Sweden. However, major differences were found in how the Australian and
      Swedish media framed the pandemic in terms of responsibility, self-efficacy, and
      uncertainty. In Australia, responsibility was predominantly reported negatively,
      blaming various organisations for a lack of information, compared to Sweden where
      responsibility was placed on the community to help protect public health.
      Furthermore, there was limited self-efficacy measures reported in the Australian
      media compared to Sweden and Sweden's media was more transparent about the
      uncertainties of the pandemic. CONCLUSIONS: This study affirms the association
      between the framing of health messages in the media and the public's perception
      of risk and related behaviour. Governments need to actively incorporate the media
      into pandemic communication planning.

PMID- 23873632
TI  - RANKL inhibition with denosumab does not influence 3-year progression of aortic
      calcification or incidence of adverse cardiovascular events in postmenopausal
      women with osteoporosis and high cardiovascular risk.
AB  - Atherosclerosis and osteoporosis are chronic diseases that progress with age, and
      studies suggest aortic calcification, an indicator of atherosclerosis, is
      inversely associated with bone mineral density (BMD). The osteoprotegerin
      (OPG)/receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) system has been
      proposed as a shared regulatory system for bone and vasculature. Denosumab
      (DMAb), a monoclonal antibody against RANKL, improved BMD and reduced fracture
      risk in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6
      Months (FREEDOM) trial. We evaluated whether or not treatment with DMAb
      influenced progression of aortic calcification (AC) and incidence of
      cardiovascular (CV) adverse events. We included 2363 postmenopausal women with
      osteoporosis (1142 placebo, 1221 DMAb), selected from 7808 participants in the
      FREEDOM trial (3906 placebo, 3902 DMAb), at high risk of CV events according to
      modified Raloxifene Use for the Heart (RUTH) criteria. CV adverse events were
      reported by participants. AC scores were assessed using a semiquantitative method
      from lateral spine X-rays. Change in AC score from baseline to 12 (n = 1377), 24
      (n = 1231), and 36 months (n = 1045) was calculated as AC score at follow-up
      minus AC score at baseline. AC progression was defined as change in AC score >0.
      Baseline characteristics, CV risk factors, and AC scores were similar between
      treatment groups. Mean age of participants was 74 years (range, 60-90), 88% were
      white, and 77% had AC score >0 at baseline. Frequency of AC progression over 3
      years did not differ between women in placebo (22%) and DMAb (22%) groups (p =
      0.98). AC progression did not differ between treatment groups when analyzed by
      baseline estimated glomerular filtration rate or by baseline AC scores. Frequency
      of CV adverse events did not differ between placebo (40%) and DMAb (38%) groups
      (p = 0.26). In conclusion, DMAb treatment had no effect on progression of AC or
      incidence of CV adverse events compared to placebo.

PMID- 23873633
TI  - Ultrasound for monitoring controlled ovarian stimulation: a systematic review and
      meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy and safety of monitoring controlled ovarian
      stimulation (COS) using ultrasonography. METHODS: We performed a search in April
      2013 for randomized controlled trials (RCTs). Studies that compared different
      methods for monitoring COS, including ultrasound assessment of follicles (alone
      or combined with hormonal assessment), in at least one group were considered
      eligible. RESULTS: The search retrieved 1515 records, six of which were eligible.
      Five studies were included that compared ultrasonography alone with
      ultrasonography and hormonal assessment (estradiol and/or progesterone) and one
      study compared 2D and 3D ultrasound monitoring. None of the included studies
      reported on live birth. Four of the five studies reported on clinical pregnancy
      (RR, 0.95; 95% CI, 0.78-1.16; n = 611); the confidence interval (CI) was somewhat
      wide, but allowed us to conclude that ultrasonography alone differs little from
      ultrasonography combined with hormonal assessment. Three studies reported on the
      number of oocytes retrieved (mean difference (MD), 0.8 oocytes; 95% CI, -0.4 to
      2.0; n = 474); the CI was somewhat wide and did not permit us to conclude whether
      ultrasonography alone is better than or similar to ultrasonography and hormonal
      assessment for this outcome. All five studies reported on ovarian
      hyperstimulation syndrome (OR, 1.02; 95% CI, 0.47-2.25; n = 725) and only one
      study reported on miscarriage (RR, 0.37; 95% CI, 0.07-1.79; n = 45); for these
      two outcomes, the CI was very wide and did not permit us to conclude whether
      ultrasonography alone is better, similar or less effective than ultrasonography
      combined with hormonal assessment. For the study comparing 2D and 3D ultrasound,
      the reported outcomes were clinical pregnancy (RR, 1.00; 95% CI, 0.58-1.73, n =
      72) and the number of oocytes retrieved (MD, -0.4 oocytes; 95% CI, -3.6 to 2.9; n
      = 72); for both, the CI was very wide and did not permit us to conclude whether
      use of 3D ultrasound is better, similar or less effective than use of 2D
      ultrasound. CONCLUSIONS: Current evidence suggests that monitoring COS only with
      ultrasonography is unlikely to substantially alter the chances of achieving a
      clinical pregnancy and the number of oocytes retrieved is similar to that when
      monitoring with ultrasonography and hormonal assessment. For the other outcomes
      and comparisons, the available data are inconclusive. We believe that more
      studies evaluating the optimal procedure for monitoring COS are needed.

PMID- 23873635
TI  - Triple oral antithrombotic therapy in atrial fibrillation and coronary artery
      stenting.
AB  - Patients with atrial fibrillation affected by an acute coronary syndrome have
      indications for oral anticoagulation and dual antiplatelet therapy with aspirin
      and a P2Y12 adenosine diphosphate receptor inhibitor after coronary artery
      stenting. The concurrent use of all 3 agents, termed triple oral antithrombotic
      therapy, significantly increases the risk of bleeding. To date, there is a lack
      of evidence on the proper combination and duration of anticoagulant and
      antiplatelet agents in patients with indications for both therapies. As such,
      care has been guided by expert opinion, and there is wide variation in clinician
      practice. In this review, the latest evidence on the risks and benefits of triple
      oral antithrombotic therapy in patients with atrial fibrillation after coronary
      artery stenting is summarized. We discuss the clinical risk scores useful in
      guiding the prediction of stroke, bleeding, and stent thrombosis. Additionally,
      we highlight where additional evidence is needed to determine the proper balance
      of anticoagulant and antiplatelet agents in this patient population. 

PMID- 23873634
TI  - Concise review: clinical programs of stem cell therapies for liver and pancreas.
AB  - Regenerative medicine is transitioning into clinical programs using
      stem/progenitor cell therapies for repair of damaged organs. We summarize those
      for liver and pancreas, organs that share endodermal stem cell populations,
      biliary tree stem cells (hBTSCs), located in peribiliary glands. They are
      precursors to hepatic stem/progenitors in canals of Hering and to committed
      progenitors in pancreatic duct glands. They give rise to maturational lineages
      along a radial axis within bile duct walls and a proximal-to-distal axis starting
      at the duodenum and ending with mature cells in the liver or pancreas. Clinical
      trials have been ongoing for years assessing effects of determined stem cells
      (fetal-liver-derived hepatic stem/progenitors) transplanted into the hepatic
      artery of patients with various liver diseases. Immunosuppression was not
      required. Control subjects, those given standard of care for a given condition,
      all died within a year or deteriorated in their liver functions. Subjects
      transplanted with 100-150 million hepatic stem/progenitor cells had improved
      liver functions and survival extending for several years. Full evaluations of
      safety and efficacy of transplants are still in progress. Determined stem cell
      therapies for diabetes using hBTSCs remain to be explored but are likely to occur
      following ongoing preclinical studies. In addition, mesenchymal stem cells (MSCs)
      and hematopoietic stem cells (HSCs) are being used for patients with chronic
      liver conditions or with diabetes. MSCs have demonstrated significant effects
      through paracrine signaling of trophic and immunomodulatory factors, and there is
      limited evidence for inefficient lineage restriction into mature parenchymal or
      islet cells. HSCs' effects are primarily via modulation of immune mechanisms.

PMID- 23873637
TI  - Transaortic valve implantation via occluded saphenous vein grafts--a novel access
      route for transcatheter aortic valve delivery.
AB  - Transaortic valve implantation via direct aortic puncture has been shown to be
      useful alternative to more traditional access routes. In patients with previously
      placed ascending aorta saphenous vein grafts, access to the aortic valve may be
      limited. We therefore sought to detail the utility of a new approach for
      accessing the ascending aorta during transcatheter aortic valve implantation via
      the hood of previously placed saphenous vein grafts.

PMID- 23873636
TI  - P2X1 receptor-mediated inhibition of the proliferation of human coronary smooth
      muscle cells involving the transcription factor NR4A1.
AB  - Adenine nucleotides acting at P2X1 receptors are potent vasoconstrictors.
      Recently, we demonstrated that activation of adenosine A2B receptors on human
      coronary smooth muscle cells inhibits cell proliferation by the induction of the
      nuclear receptor subfamily 4, group A, member 1 (NR4A1; alternative notation
      Nur77). In the present study, we searched for long-term effects mediated by P2X1
      receptors by analyzing receptor-mediated changes in cell proliferation and in the
      expression of NR4A1. Cultured human coronary smooth muscle cells were treated
      with selective receptor ligands. Effects on proliferation were determined by
      counting cells and measuring changes in impedance. The induction of transcription
      factors was assessed by qPCR. The P2X receptor agonist alpha,beta-methylene-ATP
      and its analog beta,gamma-methylene-ATP inhibited cell proliferation by about 50
      % after 5 days in culture with half-maximal concentrations of 0.3 and 0.08 MUM,
      respectively. The effects were abolished or markedly attenuated by the P2X1
      receptor antagonist NF449 (carbonylbis-imino-benzene-triylbis
      (carbonylimino)tetrakis-benzene-1,3-disulfonic acid; 100 nM and 1 MUM).
      alpha,beta-methylene-ATP and beta,gamma-methylene-ATP applied for 30 min to 4 h
      increased the expression of NR4A1; NF449 blocked or attenuated this effect. Small
      interfering RNA directed against NR4A1 diminished the antiproliferative effects
      of alpha,beta-methylene-ATP and beta,gamma-methylene-ATP. alpha,beta-methylene
      ATP (0.1 to 30 MUM) decreased migration of cultured human coronary smooth muscle
      cells in a chamber measuring changes in impedance; NF449 blocked the effect. In
      conclusion, our results demonstrate for the first time that adenine nucleotides
      acting at P2X1 receptors inhibit the proliferation of human coronary smooth
      muscle cells via the induction of the early gene NR4A1. 

PMID- 23873638
TI  - Biochemical characterization and antitumor study of L-glutaminase from Bacillus
      cereus MTCC 1305.
AB  - L-Glutaminase (E.C.3.5.2.1) extracellularly produced by Bacillus cereus MTCC 1305
      was purified to apparent homogeneity with a fine band. The molecular weight of
      native enzyme and its subunit were found to be approximately 140 and 35 kDa,
      respectively, which indicates its homotetrameric nature. The substrate
      specificity test of this enzyme showed its specificity for L-glutamine. The
      purified enzyme showed maximum activity at optimum pH 7.5 and temperature 35 
      degrees C. The enzyme retained stability up to 50 and 20 % even after treatment
      at 50 and 55  degrees C, respectively, for 30 min. Monovalent cations (Na(+),
      K(+)) and phosphate ion activated the enzyme activity, while divalent cations
      (Mg(2+), Mn(2+), Zn(2+), Pb(2+), Ca(2+), Co(2+), Hg(2+), Cd(2+), Cu(2+))
      inhibited its activity. Reducing agents (cysteine, glutathione, dithiothreitol, L
      ascorbic acid, and beta-mercaptoethanol) stimulated its activity, whereas thiol
      binding agents (iodoacetamide, p-chloromercuribenzoic acid) resulted in the
      inhibition of this enzyme. Kinetic parameters, K m, V max, K cat, of purified
      enzyme were found to be 6.25 mM, 100 MUmol/min/mg protein and 2.22 * 10(2) M(
      1)s(-1), respectively. The gradual inhibition in growth of hepatocellular
      carcinoma (Hep-G2) cell lines was found with IC50 value of 82.27 MUg/ml in the
      presence of different doses of L-glutaminase (10-100 MUg/ml). 

PMID- 23873639
TI  - Improving the mixing performances of rice straw anaerobic digestion for higher
      biogas production by computational fluid dynamics (CFD) simulation.
AB  - As a lignocellulose-based substrate for anaerobic digestion, rice straw is
      characterized by low density, high water absorbability, and poor fluidity. Its
      mixing performances in digestion are completely different from traditional
      substrates such as animal manures. Computational fluid dynamics (CFD) simulation
      was employed to investigate mixing performances and determine suitable stirring
      parameters for efficient biogas production from rice straw. The results from CFD
      simulation were applied in the anaerobic digestion tests to further investigate
      their reliability. The results indicated that the mixing performances could be
      improved by triple impellers with pitched blade, and complete mixing was easily
      achieved at the stirring rate of 80 rpm, as compared to 20-60 rpm. However,
      mixing could not be significantly improved when the stirring rate was further
      increased from 80 to 160 rpm. The simulation results agreed well with the
      experimental results. The determined mixing parameters could achieve the highest
      biogas yield of 370 mL (g TS)(-1) (729 mL (g TS(digested))(-1)) and 431 mL (g
      TS)(-1) (632 mL (g TS(digested))(-1)) with the shortest technical digestion time
      (T 80) of 46 days. The results obtained in this work could provide useful guides
      for the design and operation of biogas plants using rice straw as substrates.

PMID- 23873640
TI  - Curing the plasmid pMC1 from the poly (gamma-glutamic acid) producing Bacillus
      amyloliquefaciens LL3 strain using plasmid incompatibility.
AB  - Bacillus amyloliquefaciens LL3 is a glutamate-independent poly-gamma-glutamic
      acid (gamma-PGA) producing strain which consists of a circular chromosome
      (3,995,227 bp) and an endogenous plasmid pMC1 (6,758 bp). The study of the
      function of native plasmid and the genome-size reduction of the B.
      amyloliquefaciens LL3 strain requires elimination of the endogenous plasmid.
      Traditional plasmid-curing procedures using sodium dodecyl sulfate (SDS) or
      acridine orange combined with heat treatment have been shown to be ineffective in
      this strain. Plasmid incompatibility is an effective method for curing which has
      been studied before. In our research, the hypothetical Rep protein gene and the
      origin of replication of the endogenous plasmid were cloned into the temperature
      sensitive vector yielding the incompatible plasmid pKSV7-rep-ori. This plasmid
      was transformed into LL3 by electroporation. The analysis of the strain bearing
      incompatible plasmids after incubation at 30  degrees C for 30 generations showed
      the production of plasmid cured strains. High frequency of elimination was
      achieved with more than 93 % of detected strains showing to be plasmid-cured.
      This is the first report describing plasmid cured in a gamma-PGA producing strain
      using this method. The plasmid-cured strains showed an increase of gamma-PGA
      production by 6 % and led to a yield of 4.159 g/l, compared to 3.918 g/l in
      control and cell growth increased during the early stages of the exponential
      phase. Gel permeation chromatography (GPC) characterization revealed that the
      gamma-PGA produced by plasmid-cured strains and the wild strains were identical
      in terms of molecular weight. What is more, the further study of plasmid function
      showed that curing of the endogenous plasmid did not affect its sporulation
      efficiency. 

PMID- 23873641
TI  - Regeneration and Agrobacterium-mediated transformation of the apomictic species
      Eulaliopsis binata.
AB  - Protocols for regeneration and Agrobacterium-mediated transformation of the
      apomictic species Eulaliopsis binata were developed. Initially, seeds of four
      genotypes of E. binata were incubated on a callus induction Murashige and Skoog
      (MS) basal medium supplemented with three concentrations of 2,4
      dichlorophenoxyacetic acid (2,4-D). It was found that 36.2 % of explants
      developed highly friable callus on medium containing 3.0 mg l(-1) 2,4-D. Based on
      frequency of callus induction, the genotype Neixiang was selected for
      regeneration and transformation. Callus incubated on MS basal medium supplemented
      with 0.2 mg l(-1) alpha-naphthalene acetic acid and 6.0 mg l(-1) 6-furfuryl
      aminopurine developed shoots. Subsequently, Agrobacterium tumefaciens strain
      EHA105-harboring a plasmid pCAMBIA1381 carrying a hygromycin phosphotransferase
      (hpt) resistance gene and a synthetic green fluorescent protein (GFP) gene, both
      driven by the cauliflower mosaic virus 35S promoter-was used for transformation
      system. Putative transgenic callus was obtained following two cycles of
      hygromycin selection. Expression of the transgene(s) in putative transgenic
      callus was analyzed using the GFP detection. Molecular identification of putative
      transformed shoots was performed by polymerase chain reaction and Southern blot
      analysis to confirm presence and integration of the hpt gene. 

PMID- 23873642
TI  - Pigment production by filamentous fungi on agro-industrial byproducts: an eco
      friendly alternative.
AB  - The search for new sources of natural pigments has increased, mainly because of
      the toxic effects caused by synthetic dyes used in food, pharmaceutical, textile,
      and cosmetic industries. Fungi provide a readily available alternative source of
      natural pigments. In this context, the fungi Penicillium chrysogenum IFL1 and
      IFL2, Fusarium graminearum IFL3, Monascus purpureus NRRL 1992, and Penicillium
      vasconiae IFL4 were selected as pigments producers. The fungal identification was
      performed using ITS and part of the beta-tubulin gene sequencing. Almost all
      fungi were able to grow and produce water-soluble pigments on agro-industrial
      residues, with the exception of P. vasconiae that produced pigments only on
      potato dextrose broth. The production of yellow pigments was predominant and the
      two strains of P. chrysogenum were the largest producers. In addition, the
      production of pigments and mycotoxins were evaluated in potato dextrose agar
      using TOF-MS and TOF-MS/MS. Metabolites as roquefortine C, chrysogine were found
      in both extracts of P. chrysogenum, as well fusarenone X, diacetoxyscirpenol, and
      neosolaniol in F. graminearum extract. In the M. purpureus extract, the pigments
      monascorubrin, rubropunctatin, and the mycotoxin citrinin were found. The crude
      filtrates have potential to be used in the textile industry; nevertheless,
      additional pigment purification is required for food and pharmaceutical
      applications. 

PMID- 23873643
TI  - Synthesis, characterization, and antimicrobial activity of poly(acrylonitrile-co
      methyl methacrylate) with silver nanoparticles.
AB  - Nanotechnology is expected to open some new aspects to fight and prevent diseases
      using atomic-scale tailoring of materials. The main aim of this study is to
      biosynthesize silver nanoparticles (AgNPs) using Trichoderma viride (HQ438699);
      the metabolite of this fungus will help either in reduction of the silver nitrate
      adding active materials which will be loaded on the surface of the produced
      AgNPs. Poly(acrylonitrile-co-methyl methacrylate) copolymer (poly (AN-co-MMA))
      was grafted with the prepared AgNPs. The poly(AN-co-MMA)/AgNPs were examined
      against ten different pathogenic bacterial strains, and the result was compared
      with another four different generic antibiotics. The produced poly(AN-co
      MMA)/AgNPs showed high antibacterial activity compared with the four standard
      antibiotics. Moreover, the grafting of these AgNPs into the copolymer has
      potential application in the biomedical field. 

PMID- 23873644
TI  - Determination of optimal replicate number for validation of imprecision using
      fluorescence cell based assays: Proposed practical method.
AB  - Background: Assay validation includes determination of inherent imprecision
      across the reportable range. However specific practical guidelines for
      determinations of precision for cell based fluorescence assays performed on flow
      cytometers are currently lacking. Methods: Replicates of 10 or 20 measurements
      were obtained for flow cytometric assays developed for clinical IVD use,
      including neutrophil CD64 expression for infection/sepsis detection, fetal red
      cell enumeration for fetomaternal hemorrhage detection, human equilibrative
      nucleoside transporter 1 (hENT1) quantitation in leukocytes for possible
      correlation with drug responsiveness, and CD34+ hematopoietic stem cell (HSC)
      enumeration of apheresis products, using up to three different instrument
      platforms for each assay. For each assay, the mean, 95% confidence intervals of
      the mean (95%CI), standard deviation and coefficient of variation (CV) of
      sequential replicates were determined. Results: For all assays and most
      instrument platforms <5 replicates were found adequate to validate assay
      imprecision levels below the 5-10% CV for repeatability claimed by the
      manufacturers of these assays. Results plotted as a novel parameter derived from
      the 95%CI and the cumulative mean for replicates, termed variance factor (VF),
      provide a data driven means for determining optimal replicate numbers.
      Conclusions: The novel VF can provide information to guide the practical
      selection of optimal replicate numbers for validation of imprecision in flow
      cytometric assays. The optimal number of replicates was assay and instrument
      platform dependent. Our findings indicate 3-4 replicates are sufficient for most
      flow cytometric assays and instrument combinations, rather than the higher
      numbers suggested by CLSI guidelines for soluble analytes. (c) 2013 Clinical
      Cytometry Society.

PMID- 23873645
TI  - Highly multidrug-resistant HIV: clonal analysis and therapeutic strategies.
AB  - OBJECTIVES: There are today HIV-infected patients in therapeutic impasses because
      of highly multidrug-resistant (HMDR) viruses. We studied the distribution of
      resistance mutations at clonal level, and we analysed the therapeutic strategies
      used in such cases to achieve undetectable viraemia. METHODS: The HMDR profile
      was defined as a genotypic sensitivity score (GSS) <= 1.5 for etravirine and
      raltegravir with full resistance to darunavir. About 30 clones per gene and per
      patient were sequenced. Virtual phenotypes were determined. Efficacy of
      therapeutic strategies was evaluated by follow-up of viral loads, CD4 cell counts
      and trough concentrations of drugs. RESULTS: Among 1310 patients on treatment and
      with genotypic resistance testing, 25 (2%) were resistant to darunavir and 11
      (0.8%) had an HMDR profile. Five-hundred clones could be analysed for four of
      them. HMDR profiles were harboured by the great majority of clones and all
      resistance mutations were located on the same strains for all genes. Despite this
      and a regimen with a GSS <2.0 in three patients, they achieved a viraemia <20
      copies/mL. These results were obtained using different strategies: high doses of
      drugs; combination of antiretrovirals with full or intermediate susceptibility,
      such as tipranavir, etravirine or maraviroc; and use of alternative compounds,
      such as foscarnet or interferon. CONCLUSION: Patients with HMDR HIV were
      uncommon, but, in such cases, all resistance mutations were borne on the same
      majority strains. In this study, tipranavir was the only protease inhibitor with
      full or intermediate susceptibility. Despite very limited therapeutic options, an
      undetectable viraemia can be achieved by combining different strategies.

PMID- 23873646
TI  - Antibiotic usage in German hospitals: results of the second national prevalence
      study.
AB  - OBJECTIVES: Data on antibiotic usage (AU) are helpful for improvement of
      antibiotic stewardship. This study describes findings and targets for quality
      improvement in German hospitals identified in a national point prevalence survey
      of healthcare-associated infections and AU. METHODS: The survey was organized by
      the German National Reference Centre for Surveillance of Nosocomial Infections
      (NRZ) as part of a pan-European survey organized by the European Centre for
      Disease Prevention and Control (ECDC). Infection control personnel of
      participating hospitals were trained in methodology and performed the survey in
      September and October 2011. Data on the antimicrobials prescribed (e.g. compounds
      and indications) were analysed by the NRZ. In order to submit national data to
      the ECDC, a representative sample of 46 hospitals was generated, although other
      hospitals were invited to participate in the survey if interested. RESULTS: In
      total, 41,539 patients were surveyed in 132 hospitals. AU prevalence in these
      hospitals and in the representative sample did not differ significantly [25.5%
      (95% CI 24.5%-26.6%) and 23.3% (95% CI 21.3%-25.5%), respectively]. AU rates were
      higher compared with a previous survey in 1994. Antimicrobials were administered
      for treatment in 70% and prophylaxis in 30% of cases. Surgical prophylaxis (SP)
      was prolonged (>1 day) in 70% of cases. Indication was documented in patients'
      charts in 73% of administrations. The most frequently used agents were cefuroxime
      (14.3%), ciprofloxacin (9.8%) and ceftriaxone (7.5%). CONCLUSIONS: The study
      identified several points for improvement, e.g. the large amount of prolonged SP,
      the extensive use of broad-spectrum antibiotics and the high percentage of
      antibiotic administration without documented indication.

PMID- 23873647
TI  - Tissue penetration and antimicrobial activity of standard- and high-dose
      trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot
      infection.
AB  - OBJECTIVES: The purpose of this study was to conduct a pharmacokinetic and
      pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses
      of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic
      foot infections (DFIs). METHODS: Both viable skin/soft tissue from the infection
      site and serum were obtained at various times after antibiotic administration
      from 18 patients (6 per study group) being treated with linezolid, standard doses
      of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole
      during a follow-up clinic visit. These samples were assayed for drug
      concentrations by liquid chromatography in tandem with mass spectrometry. Patient
      sera were also utilized in time-kill assays against two strains of Staphylococcus
      aureus and three strains of beta-haemolytic streptococci. RESULTS: The mean
      tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean
      tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard
      and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for
      standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited
      inhibitory activity in time-kill assays against strains of S. aureus (0.45 +/-
      0.5 log10 cfu/mL) and beta-haemolytic streptococci (2.2 +/- 0.6 log10 cfu/mL),
      while trimethoprim/sulfamethoxazole exhibited bactericidal (>3 log kill) activity
      against all of these isolates. These findings were consistent for each sampling
      time and for high as well as standard doses of trimethoprim/sulfamethoxazole.
      CONCLUSIONS: This pharmacokinetic/pharmacodynamic study found that
      trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in
      patients with DFIs as well as bactericidal activity in serum against strains of
      S. aureus and beta-haemolytic streptococci.

PMID- 23873648
TI  - Dinuclear polypyridylruthenium(II) complexes: flow cytometry studies of their
      accumulation in bacteria and the effect on the bacterial membrane.
AB  - OBJECTIVES: To determine the energy dependency of and the contribution of the
      membrane potential to the cellular accumulation of the dinuclear complexes
      [{Ru(phen)2}2{MU-bbn}](4+) (Rubbn) and the mononuclear complexes
      [Ru(Me4phen)3](2+) and [Ru(phen)2(bb7)](2+) in Staphylococcus aureus and
      Escherichia coli, and to examine their effect on the bacterial membrane. METHODS:
      The accumulation of the ruthenium complexes in bacteria was determined using flow
      cytometry at a range of temperatures. The cellular accumulation of the ruthenium
      complexes was also determined in cells that had been incubated with the metal
      complexes in the presence or absence of metabolic stimulators or inhibitors
      and/or commercial dyes to determine the membrane potential or membrane
      permeability. RESULTS: The accumulation of ruthenium complexes in the two
      bacterial strains was shown to increase with increasing incubation temperature,
      with the relative increase in accumulation greater with E. coli, particularly for
      Rubb12 and Rubb16. No decrease in accumulation was observed for Rubb12 in ATP
      inhibited cells. While carbonyl cyanide m-chlorophenyl hydrazone (CCCP) did
      depolarize the cell membrane, no reduction in the accumulation of Rubb12 was
      observed; however, all ruthenium complexes, when incubated with S. aureus at
      concentrations twice their MIC, depolarized the membrane to a similar extent to
      CCCP. Except for the mononuclear complex [Ru(Me4phen)3](2+), incubation of any of
      the other ruthenium complexes allowed a greater quantity of the membrane
      impermeable dye TO-PRO-3 to be taken up by S. aureus. CONCLUSIONS: The results
      indicate that the potential new antimicrobial Rubbn complexes enter the cell in
      an energy-independent manner, depolarize the cell membrane and significantly
      permeabilize the cellular membrane.

PMID- 23873649
TI  - Rare occurrence of vancomycin-resistant Enterococcus faecium among livestock
      animals in China.

PMID- 23873650
TI  - Hydrogen bonding and alcohol effects in asymmetric hypervalent iodine catalysis:
      enantioselective oxidative dearomatization of phenols.

PMID- 23873651
TI  - The crystal structure of methenyltetrahydromethanopterin cyclohydrolase from
      Methanobrevibacter ruminantium.
AB  - Methenyltetrahydromethanopterin cyclohydrolase (Mch) is involved in the
      methanogenesis pathway of archaea as a C1 unit carrier where N(5) -formyl
      tetrahydromethanopterin is converted to methenyl-tetrahydromethanopterin. Mch
      from Methanobrevibacter ruminantium was cloned, purified, crystallized and its
      crystal structure solved at 1.37 A resolution. A biologically active trimer, the
      enzyme is composed of two domains including an N-terminal domain of six alpha
      helices encompassing a series of four beta-sheets and a predominantly anti
      parallel beta-sheet at the C-terminus flanked on one side by alpha-helices.
      Sequence and structural alignments have helped identify residues involved in
      substrate binding and trimer formation.

PMID- 23873652
TI  - Spontaneous translocation of antitumor oxaliplatin, its enantiomeric analogue,
      and Cisplatin from one strand to another in double-helical DNA.
AB  - Oxaliplatin and cisplatin belong to the class of platinum-based anticancer
      agents. Formation of DNA adducts by these complexes and the consequences for its
      structure and function, is the mechanistic paradigm by which these drugs exert
      their antitumor activity. We show that employing short oligonucleotide duplexes
      containing single, site-specific 1,3-intrastrand cross-links of oxaliplatin, its
      enantiomeric analogue, or cisplatin and by using gel electrophoresis that under
      physiological conditions the coordination bonds between platinum and the N7
      position of guanine residues involved in the cross-links of the Pt(II) complexes
      can be cleaved. This cleavage may lead to linkage isomerization reactions between
      these metallodrugs and double-helical DNA. For instance, approximately 25 % 1,3
      intrastrand cross-links of the platinum complexes isomerized after 192 h (at 310
      K in 200 mM NaClO4). Differential scanning calorimetry of duplexes containing
      single, site-specific cross-links of oxaliplatin, its enantiomeric analogue, and
      cisplatin reveals that one of the driving forces that leads to the lability of
      DNA cross-links of these metallodrugs is a difference between the thermodynamic
      destabilization induced by the cross-link and by the adduct into which it could
      isomerize. The rearrangements may proceed in the way that cross-links originally
      formed in one strand of the DNA can spontaneously translocate from one DNA strand
      to its complementary counterpart, which may evoke walking of the platinum complex
      on DNA molecule. In addition, the differences in the kinetics of the
      rearrangement reactions and the thermodynamic destabilization of DNA observed for
      adducts of oxaliplatin and its enantiomeric analogue confirm that the chirality
      at the carrier 1,2-diaminocyclohexane ligand can considerably affect structural
      and other physical properties of DNA adducts and consequently their biological
      effects. In aggregate, interesting generalization of the results described in
      this work might be that the migration of oxaliplatin, its enantiomeric analogue,
      or cisplatin from one strand to another in double-helical DNA controlled by
      energetic signatures of these agents might contribute to a better understanding
      of their cytotoxic and mutagenic potential.

PMID- 23873653
TI  - A model combining excess and relative mortality for population-based studies.
AB  - Considering expected mortality provides an attractive approach to analyse
      mortality of population-based cohorts of patients presenting with a chronic
      disease. Two classes of methods are available: either modelling the excess
      mortality using an additive hazard model or modelling the relative mortality
      using a multiplicative hazard model. Because these two models are informative to
      look for factors associated with mortality related to a chronic disease, we
      developed an alternative model modelling both the excess and the relative
      mortality. We generalised Andersen and Vaeth's model to fit covariates and obtain
      directly an estimation of the Excess Mortality Ratio and Relative Mortality Ratio
      for each covariate. We assessed the performances of the combined model by using
      simulations, and it appeared satisfactorily. We illustrate the combined model by
      data collected in patients presenting with end-stage renal disease and treated by
      dialysis. The combined model offers the possibility of performing pure additive
      and multiplicative models and thus to compare their log-likelihoods. The combined
      model appears useful to select one of these pure models or to conclude to the
      need of modelling both excess and relative mortality. In this latter case, our
      model enabled better describing the effect of covariates on the excess and
      relative mortality.

PMID- 23873654
TI  - Campylobacter jejuni colonization and population structure in urban populations
      of ducks and starlings in New Zealand.
AB  - A repeated cross-sectional study was conducted to determine the prevalence of
      Campylobacter spp. and the population structure of C. jejuni in European
      starlings and ducks cohabiting multiple public access sites in an urban area of
      New Zealand. The country's geographical isolation and relatively recent history
      of introduction of wild bird species, including the European starling and mallard
      duck, create an ideal setting to explore the impact of geographical separation on
      the population biology of C. jejuni, as well as potential public health
      implications. A total of 716 starling and 720 duck fecal samples were collected
      and screened for C. jejuni over a 12 month period. This study combined molecular
      genotyping, population genetics and epidemiological modeling and revealed: (i)
      higher Campylobacter spp. isolation in starlings (46%) compared with ducks (30%),
      but similar isolation of C. jejuni in ducks (23%) and starlings (21%), (ii)
      significant associations between the isolation of Campylobacter spp. and host
      species, sampling location and time of year using logistic regression, (iii)
      evidence of population differentiation, as indicated by FST , and host-genotype
      association with clonal complexes CC ST-177 and CC ST-682 associated with
      starlings, and clonal complexes CC ST-1034, CC ST-692, and CC ST-1332 associated
      with ducks, and (iv) greater genetic diversity and genotype richness in ducks
      compared with starlings. These findings provide evidence that host-associated
      genotypes, such as the starling-associated ST-177 and ST-682, represent lineages
      that were introduced with the host species in the 19th century. The isolation of
      sequence types associated with human disease in New Zealand indicate that wild
      ducks and starlings need to be considered as a potential public health risk,
      particularly in urban areas.

PMID- 23873655
TI  - Relaxin modulates human and rat hepatic myofibroblast function and ameliorates
      portal hypertension in vivo.
AB  - Active myofibroblast (MF) contraction contributes significantly to the increased
      intrahepatic vascular resistance that is the primary cause of portal hypertension
      (PHT) in cirrhosis. We sought proof of concept for direct therapeutic targeting
      of the dynamic component of PHT and markers of MF activation using short-term
      administration of the peptide hormone relaxin (RLN). We defined the portal
      hypotensive effect in rat models of sinusoidal PHT and the expression, activity,
      and function of the RLN-receptor signaling axis in human liver MFs. The effects
      of RLN were studied after 8 and 16 weeks carbon tetrachloride intoxication,
      following bile duct ligation, and in tissue culture models. Hemodynamic changes
      were analyzed by direct cannulation, perivascular flowprobe, indocyanine green
      imaging, and functional magnetic resonance imaging. Serum and hepatic nitric
      oxide (NO) levels were determined by immunoassay. Hepatic inflammation was
      assessed by histology and serum markers and fibrosis by collagen proportionate
      area. Gene expression was analyzed by quantitative reverse-transcription
      polymerase chain reaction (qRT-PCR) and western blotting and hepatic stellate
      cell (HSC)-MF contractility by gel contraction assay. Increased expression of RLN
      receptor (RXFP1) was shown in HSC-MFs and fibrotic liver diseases in both rats
      and humans. RLN induced a selective and significant reduction in portal pressure
      in pathologically distinct PHT models, through augmentation of intrahepatic NO
      signaling and a dramatic reduction in contractile filament expression in HSC-MFs.
      Critical for translation, RLN did not induce systemic hypotension even in
      advanced cirrhosis models. Portal blood flow and hepatic oxygenation were
      increased by RLN in early cirrhosis. Treatment of human HSC-MFs with RLN
      inhibited contractility and induced an antifibrogenic phenotype in an RXFP1
      dependent manner. CONCLUSION: We identified RXFP1 as a potential new therapeutic
      target for PHT and MF activation status.

PMID- 23873656
TI  - A general strategy for cellular reprogramming: the importance of transcription
      factor cross-repression.
AB  - Transcription factor cross-repression is an important concept in cellular
      differentiation. A bistable toggle switch constitutes a molecular mechanism that
      determines cellular commitment and provides stability to transcriptional programs
      of binary cell fate choices. Experiments support that perturbations of these
      toggle switches can interconvert these binary cell fate choices, suggesting
      potential reprogramming strategies. However, more complex types of cellular
      transitions could involve perturbations of combinations of different types of
      multistable motifs. Here, we introduce a method that generalizes the concept of
      transcription factor cross-repression to systematically predict sets of genes,
      whose perturbations induce cellular transitions between any given pair of cell
      types. Furthermore, to our knowledge, this is the first method that
      systematically makes these predictions without prior knowledge of potential
      candidate genes and pathways involved, providing guidance on systems where little
      is known. Given the increasing interest of cellular reprogramming in medicine and
      basic research, our method represents a useful computational methodology to
      assist researchers in the field in designing experimental strategies.

PMID- 23873657
TI  - Supramolecular sky-blue phosphorescent polymer iridium complexes for single
      emissive-layer organic light-emitting diodes.
AB  - Novel supramolecular phosphorescent polymers (SPPs) are synthesized as a new
      class of solution-processable electroluminescent emitters. The formation of these
      SPPs takes advantage of the efficient non-bonding assembly between bis(dibenzo-24
      crown-8)-functionalized iridium complex monomer and bis(dibenzylammonium)
      tethered co-monomer, which is monitored by (1) H NMR spectroscopy and viscosity
      measurements. These SPPs show good film morphology and an intrinsic glass
      transition with a Tg of 94-116  degrees C. Noticeably, they are highly
      photoluminescent in solid state with quantum efficiency up to ca. 78%. The
      photophysical and electroluminescent properties are strongly dependent on the
      molecular structures of the iridium complex monomers. 

PMID- 23873658
TI  - Physicochemical characterization, solubilization, and stabilization of 9
      nitrocamptothecin using pluronic block copolymers.
AB  - Solid-state properties and physicochemical characteristics of 9-nitrocamptothecin
      (9NC) were investigated with a view of molecular and bulk level understanding of
      its poor aqueous solubility and hydrolytic instability that prevent efficient
      drug delivery and pharmacological activity. 9NC bulk drug substance was found to
      be a nonhygroscopic, yellowish crystalline solid with long rectangular prism
      shaped particle morphology and a sharp melting point at 264 degrees C. Hydrolysis
      of 9NC-lactone occurs above pH 4, whereas complete conversion of lactone to
      carboxylate was recorded above pH 8. At saturated conditions, appreciable
      concentrations of 9NC-lactone were detected at pH as high as 11. 9NC undergoes
      oxidation in the presence of dimethyl sulfoxide with formation of 9NC-N-oxide.
      The total solubility of lactone and carboxylate forms of 9NC in deionized water
      was found to be less than 5 MUg/mL, whereas the solubility of 9NC-lactone in
      aqueous acidic media was determined to be approximately 2.5 MUg/mL. Incorporation
      of 10% pluronic copolymers P123, F127, and F68 in 10 mM HCl increased 9NC
      solubility by 13-fold, eightfold, and fivefold, respectively. The thermodynamic
      stability of drug-loaded pluronic micelles was evaluated under isothermal
      variable volume conditions and found F127, among all poloxamers, to offer the
      best hydrolytic protection efficacy for 9NC.

PMID- 23873659
TI  - ATF4 and HIF-1alpha in bone: an intriguing relationship.

PMID- 23873660
TI  - The long-term outcomes of transcoronary ablation of septal hypertrophy compared
      to surgical myectomy in patients with symptomatic hypertrophic obstructive
      cardiomyopathy.
AB  - OBJECTIVES: The aim of this study was to compare the long-term outcomes of
      transcoronary ablation of septal hypertrophy (TASH) with open surgical myomectomy
      (SM) in patients with symptomatic hypertrophic obstructive cardiomyopathy (HOCM).
      METHODS: We reviewed patients who underwent either procedure at our institution.
      The demographics, clinical outcomes, echocardiographic parameters, and
      complications were compared. RESULTS: Seventy patients with HOCM were treated
      with either TASH (n = 47, 26 male) or SM (n = 23, 10 male). Compared to those
      treated with SM, patients undergoing TASH were older (57+/- 14.7 years versus 47
      +/- 20.6 years, P = 0.021) and more symptomatic. A higher proportion of patients
      had syncope as a presenting feature in the TASH group compared to the SM group
      (57.5% vs. 17.4%, P = 0.002) respectively. They were also more likely to be in
      New York Heart Association (NYHA) class III/IV compared to the patients who
      underwent SM (85.1% vs. 39.1%; P < 0.001). Patients were followed for a mean
      period of 43 months (TASH) and 46 months (SM). Repeat procedures were more common
      in the TASH group (17% vs. 0%, P = 0.04) but mitral valve replacement was more
      common in the SM group (0% vs. 8.7%, P = 0.105). Symptom improvement, the rate of
      complications and all cause mortality rates were similar in both groups.
      CONCLUSIONS: TASH compares favorably with surgical myectomy with regard to
      symptom resolution, rate of complications and mortality in a tertiary referral
      centre and should be seen as an attractive alternative to surgical myectomy in
      the appropriate patient population.

PMID- 23873661
TI  - Standardized uptake value in high uptake area on positron emission tomography
      with 18F-FRP170 as a hypoxic cell tracer correlates with intratumoral oxygen
      pressure in glioblastoma.
AB  - PURPOSE: The aim of this study was to clarify the reliability of positron
      emission tomography (PET) using a new hypoxic cell tracer, 1-(2-[(18)F]fluoro-1
      [hydroxymethyl]ethoxy)methyl-2-nitroimidazole ((18)F-FRP170). PROCEDURES: Twelve
      patients with glioblastoma underwent (18)F-FRP170 PET before tumor resection.
      Mean standardized uptake value (SUV) and normalized SUV were calculated at
      regions within a tumor showing high (high-uptake area) and relatively low (low
      uptake area) accumulations of (18)F-FRP170. In these areas, intratumoral oxygen
      pressure (tpO2) was measured using microelectrodes during tumor resection.
      RESULTS: Mean tpO2 was significantly lower in the high-uptake area than in the
      low-uptake area. A significant negative correlation was evident between
      normalized SUV and tpO2 in the high-uptake area. CONCLUSION: The present findings
      suggest that high accumulation on (18)F-FRP170 PET represents viable hypoxic
      tissues in glioblastoma.

PMID- 23873662
TI  - A methyl methacrylate-HEMA-CL(n) copolymerization investigation: from kinetics to
      bioapplications.
AB  - The radical copolymerization kinetics of methyl methacrylate (MMA) and poly
      epsilon-caprolactone macromonomer functionalized with a vinyl end group (HEMA
      CL(n)) is studied using a pulsed-laser technique. The reactivity ratios for this
      system are near unity, while a linear relationship between k(p,cop), the
      copolymer-averaged propagation rate coefficient, and the composition of
      macromonomer in the feed (0-80 wt% range) is determined. At 50 wt% macromonomer
      in the feed, a 1.67 +/- 0.02 and 1.64 +/- 0.06 increase in k(p,cop)/k(p,MMA) is
      determined for HEMA-CL3 and HEMA-CL2, respectively. These macromonomers are
      adopted to synthesize nanoparticles (NPs) in the range of 100-150 nm through
      batch emulsion free radical polymerization (BEP) to produce partially degradable
      drug delivery carriers. The produced NPs are tested in 4T1 cell line and show
      excellent characteristics as carriers: they do not affect cell proliferation, and
      a relevant number of NPs, thousands per cell, are internalized.

PMID- 23873663
TI  - Structural investigation of influenza virus hemagglutinin membrane-anchoring
      peptide.
AB  - Hemagglutinin (HA), the trimeric spike of influenza virus, catalyzes fusion of
      viral and cellular membranes. We have synthesized the anchoring peptide including
      the linker, transmembrane region and cytoplasmic tail (HA-TMR-CT) in a cell-free
      system. Furthermore, to mimic the palmitoylation of three conserved cysteines
      within the CT, we chemically alkylated HA-TMR-CT using hexadecyl
      methanethiosulfonate. While the nuclear magnetic resonance spectroscopy showed
      pure and refolded peptides, the formation of multiple oligomers of higher order
      impeded further structural analysis. Circular dichroism spectroscopy of both
      alkylated and non-alkylated HA-TMR-CT revealed an alpha-helical secondary
      structure. No major impact of the fatty acids on the secondary structure was
      detected. 

PMID- 23873664
TI  - Dynamic single crystals: kinematic analysis of photoinduced crystal jumping (the
      photosalient effect).
AB  - Crystals on the move: If they are subjected to a strong light stimulus, crystals
      of the cobalt coordination compound [Co(NH3)5(NO2)]Cl(NO3) undergo sudden jumps
      and leap over distances 10(2)-10(5) times their own size to release the strain
      that accumulates in their interior. The first quantitative kinematic analysis of
      this phenomenon is reported. The observed effect could be employed for actuation
      on the macroscopic scale.

PMID- 23873665
TI  - Right- and left-handed three-helix proteins. II. Similarity and differences in
      mechanical unfolding of proteins.
AB  - Here, we study mechanical properties of eight 3-helix proteins (four right-handed
      and four left-handed ones), which are similar in size under stretching at a
      constant speed and at a constant force on the atomic level using molecular
      dynamics simulations. The analysis of 256 trajectories from molecular dynamics
      simulations with explicit water showed that the right-handed three-helix domains
      are more mechanically resistant than the left-handed domains. Such results are
      observed at different extension velocities studied (192 trajectories obtained at
      the following conditions: v = 0.1, 0.05, and 0.01 A ps(-1) , T = 300 K) and under
      constant stretching force (64 trajectories, F = 800 pN, T = 300 K). We can
      explain this by the fact, at least in part, that the right-handed domains have a
      larger number of contacts per residue and the radius of cross section than the
      left-handed domains.

PMID- 23873666
TI  - Empirical Bayes estimation of the selected treatment mean for two-stage drop-the
      loser trials: a meta-analytic approach.
AB  - Point estimation for the selected treatment in a two-stage drop-the-loser trial
      is not straightforward because a substantial bias can be induced in the standard
      maximum likelihood estimate (MLE) through the first stage selection process.
      Research has generally focused on alternative estimation strategies that apply a
      bias correction to the MLE; however, such estimators can have a large mean
      squared error. Carreras and Brannath (Stat. Med. 32:1677-90) have recently
      proposed using a special form of shrinkage estimation in this context. Given
      certain assumptions, their estimator is shown to dominate the MLE in terms of
      mean squared error loss, which provides a very powerful argument for its use in
      practice. In this paper, we suggest the use of a more general form of shrinkage
      estimation in drop-the-loser trials that has parallels with model fitting in the
      area of meta-analysis. Several estimators are identified and are shown to perform
      favourably to Carreras and Brannath's original estimator and the MLE. However,
      they necessitate either explicit estimation of an additional parameter measuring
      the heterogeneity between treatment effects or a quite unnatural prior
      distribution for the treatment effects that can only be specified after the first
      stage data has been observed. Shrinkage methods are a powerful tool for
      accurately quantifying treatment effects in multi-arm clinical trials, and
      further research is needed to understand how to maximise their utility.

PMID- 23873668
TI  - Neurosurgical treatment of anorexia nervosa: review of the literature from
      leucotomy to deep brain stimulation.
AB  - This paper reviews the literature on the surgical treatment of refractory
      anorexia nervosa (AN) and examines how this literature can inform current circuit
      models of the disease. The literature contains reports of 35 patients undergoing
      a neurosurgical procedure for the specific treatment of refractory AN, with the
      first reported operation, a lobotomy, in 1950. All patients were deemed treatment
      resistant according to contemporary standards, with the nature of the procedure
      changing with evolving surgical techniques and methods. All procedures targeted
      the limbic system and, in a majority of cases, were associated with reported
      symptomatic improvement. Neurosurgery in AN has been, and continues to be,
      reserved for patients with chronic and life-threatening illness, for whom
      conventional treatment has failed. Early procedures, which were viewed as life
      saving measures, were crude by today's standards but targeted anatomic structures
      and pathways implicated in modern models of AN. The last decade has seen a
      concerted effort in elucidating the neurocircuitry underlying prominent etiologic
      and maintaining factors in AN, including mood, anxiety and dysfunctional reward
      processing. This has translated into the development of novel, focused
      therapeutic options for patients with treatment-refractory AN.

PMID- 23873667
TI  - Identification of a metagenomic gene cluster containing a new class A beta
      lactamase and toxin-antitoxin systems.
AB  - Several reports mention the presence of antibiotic resistance genes in natural
      and polluted environments, but many studies are based on their detection via
      polymerase chain reaction (PCR amplification of known genes and not on an
      activity screening. We constructed a metagenomic fosmid bank from DNA isolated
      from a polluted river in Brussels, Belgium, the Zenne. A total of 120,000 clones
      were pooled and plated directly on solid media containing different antibiotics.
      Several clones were isolated which could grow in the presence of ampicillin. The
      DNA from several clones was extracted and subjected to restriction analysis and,
      based on their restriction pattern, two different clones were found. One of the
      clones was selected for further study as it showed a higher level of resistance
      to different beta-lactams antibiotics (ticarcilline and ceftazidime). To find out
      which gene is responsible for the resistance, an in vitro transposon mutagenesis
      was performed and clones having lost the resistance phenotype were analyzed via
      inverse PCR amplification. Several clones had an insert in a gene encoding a new
      type of beta-lactamase. The amplified fosmid DNA was fully sequenced revealing an
      insert of 41 kb containing 39 open reading frames (ORFs). Transposon insertions
      inactivating the resistance to beta-lactams were also found in the ORF upstream
      of the blaA gene, encoding an aminotransferase, suggesting a polar effect on the
      transcription of the gene downstream. In addition, other genes were found such as
      histidine biosynthesis genes, which were found to be scattered on the insert, a
      relA/spoT gene, and genes belonging to type II toxin-antitoxin system. This
      predicted system was experimentally validated in Escherichia coli using an
      inducible expression system.

PMID- 23873669
TI  - Staphylococcus aureus Penicillin-Binding Protein 2 Can Use Depsi-Lipid II Derived
      from Vancomycin-Resistant Strains for Cell Wall Synthesis.
AB  - Vancomycin-resistant Staphylococcus aureus (S. aureus) (VRSA) uses depsipeptide
      containing modified cell-wall precursors for the biosynthesis of peptidoglycan.
      Transglycosylase is responsible for the polymerization of the peptidoglycan, and
      the penicillin-binding protein 2 (PBP2) plays a major role in the polymerization
      among several transglycosylases of wild-type S. aureus. However, it is unclear
      whether VRSA processes the depsipeptide-containing peptidoglycan precursor by
      using PBP2. Here, we describe the total synthesis of depsi-lipid I, a cell-wall
      precursor of VRSA. By using this chemistry, we prepared a depsi-lipid II analogue
      as substrate for a cell-free transglycosylation system. The reconstituted system
      revealed that the PBP2 of S. aureus is able to process a depsi-lipid II
      intermediate as efficiently as its normal substrate. Moreover, the system was
      successfully used to demonstrate the difference in the mode of action of the two
      antibiotics moenomycin and vancomycin.

PMID- 23873670
TI  - Effect of ONO-5334 on bone mineral density and biochemical markers of bone
      turnover in postmenopausal osteoporosis: 2-year results from the OCEAN study.
AB  - Cathepsin K inhibitors, such as ONO-5334, are being developed for the treatment
      of postmenopausal osteoporosis. However, their relative effects on bone
      resorption and formation, and how quickly the effects resolve after treatment
      cessation, are uncertain. The aim of this study was to examine the efficacy and
      safety of 24-month treatment with ONO-5334 and to assess the effect of treatment
      cessation over 2 months. We studied 197 postmenopausal women with osteoporosis or
      osteopenia with one fragility fracture. Patients were randomized to ONO-5334 50
      mg twice daily, 100 mg or 300 mg once daily, alendronate 70 mg once weekly
      (positive control), or placebo for 24 months. After 24 months, all ONO-5334 doses
      were associated with increased bone mineral density (BMD) for lumbar spine, total
      hip, and femoral neck (p < 0.001). ONO-5334 300 mg significantly suppressed the
      bone-resorption markers urinary (u) NTX and serum and uCTX-I throughout 24 months
      of treatment and to a similar extent as alendronate; other resorption marker
      levels remained similar to placebo (fDPD for ONO-5334 300 mg qd) or were
      increased (ICTP, TRAP5b, all ONO-5334 doses). Levels of B-ALP and PINP were
      suppressed in all groups (including placebo) for approximately 6 months but then
      increased for ONO-5334 to close to baseline levels by 12 to 24 months. On
      treatment cessation, there were increases above baseline in uCTX-I, uNTX, and
      TRAP5b, and decreases in ICTP and fDPD. There were no clinically relevant safety
      concerns. Cathepsin K inhibition with ONO-5334 resulted in decreases in most
      resorption markers over 2 years but did not decrease most bone formation markers.
      This was associated with an increase in BMD; the effect on biochemical markers
      was rapidly reversible on treatment cessation.

PMID- 23873671
TI  - L-carnitine pretreatment protects slow-twitch skeletal muscles in a rat model of
      ischemia-reperfusion injury.
AB  - Ischemia-reperfusion (I/R) injury negatively affects the outcome of surgical
      interventions for amputated or severely traumatized extremities. This study aimed
      to evaluate the protective role of l-carnitine on the contractile properties of
      fast-twitch (extensor digitorum longus [EDL]) and slow-twitch (soleus [SOL])
      skeletal muscles following I/R-induced injury in a rat model. Rats were divided
      into 4 groups (1) saline pretreatment, (2) l-carnitine pretreatment, (3) saline
      pretreatment and I/R, and (4) l-carnitine pretreatment and I/R. Twitch and
      tetanic contractions in the EDL and SOL muscles in each group were recorded.
      Additionally, a fatigue protocol was performed in these muscles. Twitch and
      tetanic contraction amplitudes were lower in the EDL and SOL muscles in which I/R
      was induced (P < .01). l-Carnitine pretreatment significantly increased tetanic
      contraction amplitude in the SOL muscles following I/R (P < .01) but not in the
      EDL muscles. l-Carnitine pretreatment did not alter the fatigue response in any
      of the muscles. 

PMID- 23873672
TI  - Cystic adventitial disease of the common femoral vein: a case report and review
      of the literature.
AB  - We report on a 52-year-old female patient who presented with a 6-month history of
      right lower extremity swelling and tenderness. The patient was treated as an
      outpatient with full anticoagulation, without any improvement. Her medical
      history was significant for hypertension and high cholesterol, and she had a full
      coagulopathy profile that was negative for any hypercoagulable syndrome. On
      examination, the patient was moderately obese, with significant tenderness over
      the medial aspect of the right groin. A venous duplex examination revealed
      hypoechoic structure +/- acute deep vein thrombosis of right common femoral vein
      (CFV). A computed tomography of the venous phase revealed an eccentric
      compression over the medial wall of the right CFV. During surgical exploration,
      adventitial cystic mucinous disease was enucleated from the medial wall of the
      right CFV, and the pathological examination confirmed the diagnosis. The
      postoperative course was uneventful, and all swelling and tenderness were
      completely resolved. The patient continued to do well, and she had an
      unremarkable venous duplex evaluation at her 6-month follow-up.

PMID- 23873673
TI  - Space, color, and direction of movement: how do they affect attention?
AB  - Paying attention improves performance, but is this improvement regardless of what
      we attend to? We explored the differences in performance between attending to a
      location and attending to a feature when perceiving global motion. Attention was
      first cued to one of four locations that had coherently moving dots, while the
      remaining three had randomly moving distracter dots. Participants then viewed a
      colored display, wherein the color of the coherently moving dots was cued instead
      of location. In the third task, participants identified the location that had a
      particular cued direction of motion. Most observers reported reductions of motion
      threshold in all three tasks compared to when no cue was provided. However, the
      attentional bias generated by location cues was significantly larger than the
      bias resulting from feature cues of direction or color. This effect is consistent
      with the idea that attention is largely controlled by a fronto-parietal network
      where spatial relations are preferentially processed. On the other hand, color
      could not be used as a cue to focus attention and integrate motion. This finding
      suggests that color relies heavily on processing by ventral temporal cortical
      areas, which may have little control over the global motion areas in the dorsal
      part of the brain. 

PMID- 23873674
TI  - "What?" and "where?" versus "what is where?": the impact of task on coding of
      object form and position in the lateral occipital complex.
AB  - Fast and accurate recognition of both the identities and positions of objects in
      visual space is critical to deciphering visual environments. Studies in both
      humans and nonhuman primates have demonstrated that neural populations in ventral
      temporal visual areas are jointly tuned to both the form and position of objects,
      allowing information about the identities of objects to be "tagged" with their
      positions. Because not all behaviors demand that the identities of objects be
      associated with position information with equal precision, however, the present
      study asked whether the spatial tuning of form-encoding populations in the human
      lateral occipital complex (LOC) is sculpted by task demands. Subjects were
      scanned using functional magnetic resonance imaging while viewing matches of the
      game Rock, Paper, Scissors played with exemplar pairs from those categories.
      Subjects first performed a repetition-detection task that depended on object form
      but not position; subsequently, subjects viewed the same stimuli while
      determining the position of each pair's "winner," a task that depended upon the
      conjunction of object form and position. Compared to data from the initial scan,
      multivoxel activity patterns evoked in the lateral occipital (LO) subdivision of
      LOC while subjects judged winners showed enhanced sensitivity to the relative
      positions of objects in pairs. Although superficially consistent with dynamic
      position tuning, this effect appears to be attributable to an accompanying task
      dependent improvement in the sensitivity of LO populations to object form. The
      results thus suggest that the spatial tuning of form-encoding populations in LO
      does not depend upon the precision of spatial information demanded by a task. 

PMID- 23873675
TI  - Remapping of the environment without corollary discharges: evidence from scene
      based IOR.
AB  - Previous studies suggested that in order to perceive a stable image of the visual
      world despite constant eye movements, an efference copy of the oculomotor command
      is used to remap the representation of the environment in the brain. In two
      experiments, an inhibitory attentional component (inhibition of return-IOR) was
      used to examine whether remapping can occur also in the absence of eye movements.
      Participants were asked to maintain fixation while an unpredictive, attention
      grabbing cue appeared and was then followed by a movement of the background image
      which was artificial (random dots, Experiment 1) or composed of natural scenes
      (Experiment 2). The participants were then required to respond to a target
      stimulus that was presented either at the same location as the cue relative to
      fixation (retinotopic), or at a matching location relative to the background
      (scene based). In both experiments, an IOR effect was found in scene-based
      locations immediately after the movement of the background. We suggest that
      remapping of the inhibitory tagging, which might be a proxy for remapping of the
      visual scene, could be accomplished rapidly even without the use of an efference
      copy; the inhibitory tag seems to be anchored to the background image and to move
      together with it. 

PMID- 23873676
TI  - Effective tumor treatment by VEGF siRNA complexed with hydrophobic poly(amino
      acid)-modified polyethylenimine.
AB  - Two copolymers are designed and synthesised for siRNA delivery based on
      polyethylenimine by grafting hydrophilic acrylamide segments and hydrophobic
      poly(gamma-benzyl L-glutamate). The amphiphilic PEI-PBLG/siRNA complex
      demonstrates high gene silencing efficiency in the absence or presence of 10 vol%
      and 50 vol% sera in vitro. The anti-tumor effects in vivo are evaluated in
      luciferase-bearing mice expressing CT26 tumors. PEI-PBLG/siVEGF complex provides
      a higher and more sustained suppressive effect by reducing VEGF mRNA expression
      in the tumors, leading to higher tumor growth inhibition efficacy. Further
      studies on the potential use of the PEI-PBLG carrier system in mediating the
      silencing of genes other than VEGF or in other tumor models are recommended. 

PMID- 23873677
TI  - Two-week interval optical coherence tomography: imaging evidence on neointimal
      coverage completion after implantation of the Endeavor zotarolimus-eluting stent.
AB  - OBJECTIVE: To obtain imaging evidence by 2-week optical coherence tomography
      (OCT) on the completion of neointimal coverage (NIC; the percentage of stent
      strut coverage and thickness of the formed neointima) completion after
      implantation of the Endeavor zotarolimus-eluting stent (E-ZES). BACKGROUND:
      Despite the fact that NIC is a cardinal process in the pathomechanism of late
      stent thrombosis, little imaging information is available on morphological
      changes thereof on a short-time interval basis. METHODS: 27 Japanese patients
      with stable angina pectoris and de novo native coronary artery lesions were
      enrolled, and 27 lesions (30 implantations) were examined. OCT was performed at
      weeks 2, 4, 6, 8, and 10 after E-ZES implantation. NIC was examined using cross
      sectional OCT images obtained at the 1.0-mm intervals. RESULTS: In total, 621
      cross-sectional OCT images, which depicted 7,747 stent struts, were analyzed. The
      mean percentages of stent strut coverage at weeks 2, 4, 6, 8, and 10 after E-ZES
      implantation were 12.3, 70.4, 67.9, 86.0, and 99.2%, respectively; a marked
      increase was found between weeks 2 and 4. The mean thicknesses of the formed
      neointima were 40.2, 52.1, 48.1, 86.5, and 146.2 MUm at respective weeks, with
      the high-signal and thick neointima (146 um) at week 10. An intracoronary
      thrombus was detected in only one stent at week 4. CONCLUSIONS: The full
      circumferential coverage of the vessel wall by the high-signal neointima was
      found at as early as week 10 after E-ZES implantation, imparting a surrogate
      index for vascular healing by NIC.

PMID- 23873678
TI  - Vitamin supplements and mortality in older people.

PMID- 23873679
TI  - Limitations to the use of plasma osmolality as a hydration biomarker.

PMID- 23873680
TI  - No and low alcohol intake may have differential effects on risk of overall and
      cause-specific mortality.

PMID- 23873681
TI  - The challenge of complexity and arginine metabolism.

PMID- 23873682
TI  - Describing a taxonomy of cognitive processes for clinical trials assessing
      cognition.

PMID- 23873687
TI  - Multiple myeloma patients have a specific serum metabolomic profile that changes
      after achieving complete remission.
AB  - PURPOSE: Multiple myeloma remains an incurable disease. New approaches to develop
      better tools for improving patient prognostication and monitoring treatment
      efficacy are very much needed. In this study, we aimed to evaluate the potential
      of metabolomics by (1)H-NMR to provide information on metabolic profiles that
      could be useful in the management of multiple myeloma. EXPERIMENTAL DESIGN: Serum
      samples were collected from multiple myeloma patients at the time of diagnosis
      and after achieving complete remission. A matched control set of samples was also
      included in the study. The (1)H-NMR measurements used to obtain the metabolic
      profile for each patient were followed by the application of univariate and
      multivariate statistical analyses to determine significant differences. RESULTS:
      Metabolic profiles of multiple myeloma patients at diagnosis exhibited higher
      levels of isoleucine, arginine, acetate, phenylalanine, and tyrosine, and
      decreased levels of 3-hydroxybutyrate, lysine, glutamine, and some lipids
      compared with the control set. A similar analysis conducted in multiple myeloma
      patients after achieving complete remission indicated that some of the metabolic
      changes (i.e., glutamine, cholesterol, lysine) observed at diagnosis displayed a
      variation in the opposite direction upon responding to treatment, thus
      contributing to multiple myeloma patients having a closer metabolic profile to
      those of healthy individuals after the disappearance of major disease
      manifestations. CONCLUSIONS: The results highlight the potential of metabolic
      profiles obtained by 1H-NMR in identifying multiple myeloma biomarkers that may
      be useful to objectively discriminate individuals with and without multiple
      myeloma, and monitor response to treatment.

PMID- 23873688
TI  - Anti-PD-1 antibody therapy potently enhances the eradication of established
      tumors by gene-modified T cells.
AB  - PURPOSE: To determine the antitumor efficacy and toxicity of a novel combination
      approach involving adoptive T-cell immunotherapy using chimeric antigen receptor
      (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression.
      EXPERIMENTAL DESIGN: We examined whether administration of a PD-1 blocking
      antibody could increase the therapeutic activity of CAR T cells against two
      different Her-2(+) tumors. The use of a self-antigen mouse model enabled
      investigation into the efficacy, mechanism, and toxicity of this combination
      approach. RESULTS: In this study, we first showed a significant increase in the
      level of PD-1 expressed on transduced anti-Her-2 CD8(+) T cells following antigen
      specific stimulation with PD-L1(+) tumor cells and that markers of activation and
      proliferation were increased in anti-Her-2 T cells in the presence of anti-PD-1
      antibody. In adoptive transfer studies in Her-2 transgenic recipient mice, we
      showed a significant improvement in growth inhibition of two different Her-2(+)
      tumors treated with anti-Her-2 T cells in combination with anti-PD-1 antibody.
      The therapeutic effects observed correlated with increased function of anti-Her-2
      T cells following PD-1 blockade. Strikingly, a significant decrease in the
      percentage of Gr1(+) CD11b(+) myeloid-derived suppressor cells (MDSC) was
      observed in the tumor microenvironment of mice treated with the combination
      therapy. Importantly, increased antitumor effects were not associated with any
      autoimmune pathology in normal tissue expressing Her-2 antigen. CONCLUSION: This
      study shows that specifically blocking PD-1 immunosuppression can potently
      enhance CAR T-cell therapy that has significant implications for potentially
      improving therapeutic outcomes of this approach in patients with cancer.

PMID- 23873689
TI  - The IL-18 antagonist IL-18-binding protein is produced in the human ovarian
      cancer microenvironment.
AB  - PURPOSE: Interleukin (IL)-18 is an immune-enhancing cytokine, which induces IFN
      gamma production, T-helper 1 responses, and antitumor effects. In turn, IFN-gamma
      stimulates IL-18-binding protein production, which blocks IL-18 activity. In view
      of the potential use of IL-18 in epithelial ovarian cancer (EOC) immunotherapy,
      here, we studied IL-18BP expression and its regulation by cytokines in EOC cells
      in vitro and in vivo. EXPERIMENTAL DESIGN: Expression and production of IL-18BP
      in EOC cell lines, primary ovarian carcinomas, and the corresponding normal
      tissues, patients' serum, and ascites were investigated by immunochemistry,
      ELISA, screening of gene expression profiles, and reverse-transcription PCR.
      RESULTS: Analysis of gene expression profiles revealed that IL18BP mRNA is
      increased in EOC tumors compared with normal ovary cells. Release of IL-18BP was
      detectable in EOC sera and to a greater extent in the ascites, indicating
      production at the tumor site. Indeed, immunochemical analyses on cells isolated
      from the ascites and on tumor sections indicated that IL-18BP is expressed in
      both tumor cells and tumor-associated leukocytes, which displayed a CD3-CD20
      NKp46-CD13+CD14low phenotype. EOC cell lines do not constitutively express IL
      18BP. However, its release is inducible both by IFN-gamma stimulation in vitro
      and by xenotransplantation of EOC cells in immune-deficient mice, suggesting a
      role for the microenvironment. In vitro experiments and immunochemistry indicated
      that IL-27 is also involved in IL-18BP upregulation in EOC cell lines and primary
      cells through STAT1 activation. Together, these data indicate that IL-18BP, which
      is produced in EOC in response to microenvironmental factors, may inhibit
      endogenous or exogenous IL-18 activity.

PMID- 23873690
TI  - Novel role of MDA-9/syntenin in regulating urothelial cell proliferation by
      modulating EGFR signaling.
AB  - PURPOSE: Urothelial cell carcinoma (UCC) rapidly progresses from superficial to
      muscle-invasive tumors. The key molecules involved in metastatic progression and
      its early detection require clarification. The present study defines a seminal
      role of the metastasis-associated gene MDA-9/Syntenin in UCC progression.
      EXPERIMENTAL DESIGN: Expression pattern of MDA-9/Syntenin was examined in 44
      primary UCC and the impact of its overexpression and knockdown was examined in
      multiple cells lines and key findings were validated in primary tumors. RESULTS:
      Significantly higher (P=0.002-0.003) expression of MDA-9/Syntenin was observed in
      64% (28 of 44) of primary tumors and an association was evident with stage
      (P=0.01), grade (P=0.03), and invasion status (P=0.02). MDA-9/Syntenin
      overexpression in nontumorigenic HUC-1 cells increased proliferation (P=0.0012),
      invasion (P=0.0001), and EGF receptor (EGFR), AKT, phosphoinositide 3-kinase
      (PI3K), and c-Src expression. Alteration of beta-catenin, E-cadherin, vimentin,
      claudin-1, ZO-1, and T-cell factor-4 (TCF4) expression was also observed. MDA
      9/Syntenin knockdown in three UCC cell lines reversed phenotypic and molecular
      changes observed in the HUC-1 cells and reduced in vivo metastasis. Key molecular
      changes observed in the cell lines were confirmed in primary tumors. A physical
      interaction and colocalization of MDA-9/Syntenin and EGFR was evident in UCC cell
      lines and primary tumors. A logistic regression model analysis revealed a
      significant correlation between MDA-9/Syntenin:EGFR and MDA-9/Syntenin:AKT
      expressions with stage (P=0.04, EGFR; P=0.01, AKT). A correlation between MDA
      9/Syntenin:beta-catenin coexpression with stage (P=0.03) and invasion (P=0.04)
      was also evident. CONCLUSIONS: Our findings indicate that MDA-9/Syntenin might
      provide an attractive target for developing detection, monitoring, and
      therapeutic strategies for managing UCC.

PMID- 23873691
TI  - Phase I study of BIIB028, a selective heat shock protein 90 inhibitor, in
      patients with refractory metastatic or locally advanced solid tumors.
AB  - PURPOSE: Heat shot protein 90 (Hsp90) is a ubiquitous molecular chaperone
      involved in protein folding, activation, and assembly, including key mediators of
      signal transduction, cell-cycle control, and transcriptional regulation. We
      conducted a phase I dose-finding and pharmacokinetic/pharmacodynamic study of
      BIIB028, a prodrug designed to inhibit Hsp90 activity. EXPERIMENTAL DESIGN:
      Patients with advanced solid tumors were enrolled and received escalating doses
      of BIIB028 intravenously twice a week in 21-day cycles (3+3 design). Response was
      evaluated after two cycles. RESULTS: Forty-one patients received doses of 6 to
      192 mg/m2. The maximum tolerated dose was 144 mg/m2. Dose-limiting toxicities
      were syncope (n=1) and fatigue (n=1). Common toxicities at least possibly related
      to drug were grades 1 to 2, including fatigue (46%), diarrhea (44%), nausea
      (44%), vomiting (29%), hot flushes (29%), and abnormal dreams (17%). The
      concentration-time curves for day 1 and day 18 for both prodrug and active
      metabolite (CF2772) showed a negligible difference. There was a dose-dependent
      increase in plasma exposure for BIIB028 (CF3647) and CF2772 with plasma half-life
      of 0.5 and 2.1 hours, respectively. Pharmacodynamic analyses showed significant
      increases in Hsp70 in peripheral blood mononuclear cells and significantly
      decreased circulating human EGF receptor-2 extracellular domain in all patients
      who received BIIB028 at dose levels of 48 mg/m2 or more. Stable disease for at
      least eight cycles (24 weeks) was achieved in 5 (12%) patients (for durations of
      6, 6, 8, 12.5, and 19 months). CONCLUSION: BIIB028 is a well-tolerated molecule
      that showed target impact and was associated with prolonged stable disease in two
      patients.

PMID- 23873693
TI  - Estimation of the treatment effect in the presence of non-compliance and missing
      data.
AB  - Treatment non-compliance and missing data are common problems in clinical trials.
      Non-compliance is a broad term including any kind of deviation from the assigned
      treatment protocol, such as dose modification, treatment discontinuation or
      switch, often resulting in missing values. Missing values and treatment non
      compliance may bias study results. Follow-up of all patients until the planned
      end of treatment period irrespective of their protocol adherence may provide
      useful information on the effectiveness of a study drug, taking the actual
      compliance into account. In this paper, we consider non-compliance as
      discontinuation of treatment and assume that the endpoint of interest is recorded
      for some non-complying patients after treatment discontinuation. As a result, the
      patient's longitudinal profile is dividable into on- and off-treatment
      observations. Within the framework of depression trials, which usually show a
      considerably high amount of dropouts, we compare different analysis strategies
      including both on- and off-treatment observations to gain insight into how the
      additional use of off-treatment data may affect the trial's outcome. We compare
      naive strategies, which simply ignore off-treatment data or treat on- and off
      treatment data in the same way, with more complex strategies based on piecewise
      linear mixed models, which assume different treatment effects for on- and off
      treatment data. We show that naive strategies may considerably overestimate
      treatment effects. Therefore, it is worthwhile to follow up as many patients as
      possible until the end of their planned treatment period irrespective of
      compliance, including all available data in an analysis that accounts for the
      different treatment conditions.

PMID- 23873692
TI  - Downregulation of hematopoietic MUC1 during experimental colitis increases tumor
      promoting myeloid-derived suppressor cells.
AB  - PURPOSE: MUC1 is a tumor-associated antigen that is aberrantly expressed in
      cancer and inflammatory bowel disease (IBD). Even though immune cells express low
      MUC1 levels, their modulations of MUC1 are important in tumor progression.
      Consistent with previous clinical data that show increased myeloid-derived
      suppressor cells (MDSCs) in IBD, we now show that downregulation of MUC1 on
      hematopoietic cells increases MDSCs in IBD, similar to our data in tumor-bearing
      mice. We hypothesize that MDSC expansion in IBD is critical for tumor
      progression. EXPERIMENTAL DESIGN: To mechanistically confirm the linkage between
      Muc1 downregulation and MDSC expansion, we generated chimeric mice that did not
      express Muc1 in the hematopoietic compartment (KO->WT). These mice were used in
      two models of colitis and colitis-associated cancer (CAC) and their responses
      were compared with wild-type (WT) chimeras (WT->WT). RESULTS: KO->WT mice show
      increased levels of MDSCs during colitis and increased protumorigenic signaling
      in the colon during CAC, resulting in larger colon tumors. RNA and protein
      analysis show increased upregulation of metalloproteinases, collagenases,
      defensins, complements, growth factors, cytokines, and chemokines in KO->WT mice
      as compared with WT->WT mice. Antibody-mediated depletion of MDSCs in mice during
      colitis reduced colon tumor formation during CAC. CONCLUSION: Development of CAC
      is a serious complication of colitis and our data highlight MDSCs as a targetable
      link between inflammation and cancer. In addition, the lack of MUC1 expression on
      MDSCs can be a novel marker for MDSCs, given that MDSCs are still not well
      characterized in human cancers.

PMID- 23873694
TI  - Nuclear genes with sex bias in Ruditapes philippinarum (Bivalvia, veneridae):
      Mitochondrial inheritance and sex determination in DUI species.
AB  - Mitochondria are inherited maternally in most metazoans, but in bivalves with
      Doubly Uniparental Inheritance (DUI) a mitochondrial lineage is transmitted
      through eggs (F-type), and another through sperm (M-type). In DUI species, a sex
      ratio distortion of the progeny was observed: some females produce a female
      biased offspring (female-biased family), others a male-biased progeny (male
      biased family), and others a 50:50 sex-ratio. A peculiar segregation pattern of M
      type mitochondria in DUI organisms appears to be correlated with the sex bias of
      these families. According to a proposed model for the inheritance of M-type
      mitochondria in DUI, the transmission of sperm mitochondria is controlled by
      three nuclear genes, named W, X, and Z. An additional S gene with different
      dosage effect would be involved in sex determination. In this study, we analyzed
      structure and localization of three transcripts (psa, birc, and anubl1) with
      specific sex and family biases in the Manila clam Ruditapes philippinarum. In
      situ hybridization confirmed the localization of these transcripts in gametogenic
      cells. In other animals, homologs of these genes are involved in reproduction and
      ubiquitination. We hypothesized that these genes may have a role in sex
      determination and could also be responsible for the maintenance/degradation of
      spermatozoon mitochondria during embryo development of the DUI species R.
      philippinarum, so that we propose them as candidate factors of the W/X/Z/S
      system.

PMID- 23873695
TI  - Enantiomeric separation of 13 new amphetamine-like designer drugs by capillary
      electrophoresis, using modified-B-cyclodextrins.
AB  - An easy-to-prepare chiral CE method for the enantiomeric separation of 13 new
      amphetamine-like designer drugs, using CDs as chiral selectors, was developed.
      Sulfated-beta-CD was found to be the best chiral selector among the three used
      (sulfated-beta-CD, caroboxymethyl-beta-CD, dimethyl-beta-CD). The separation of
      the analytes was achieved in a fused-silica gel capillary at 20  degrees C using
      an applied voltage of +25 kV. The optimized background electrolyte consisted of
      63.5 mM H3 PO4 and 46.9 mM NaOH in water. Several electrophoretic parameters such
      as CD type, CD concentration (1 - 40 mg/mL), buffer pH (2.6, 3.6, 5.0, 6.0),
      length of the capillary (70 - 40 cm total length), amount of the organic solvent
      (methanol and acetonitrile) were investigated and optimized.

PMID- 23873696
TI  - Trapping formaldehyde in the homogeneous catalytic reduction of carbon dioxide.

PMID- 23873697
TI  - Identification in Marinomonas mediterranea of a novel quinoprotein with glycine
      oxidase activity.
AB  - A novel enzyme with lysine-epsilon oxidase activity was previously described in
      the marine bacterium Marinomonas mediterranea. This enzyme differs from other l
      amino acid oxidases in not being a flavoprotein but containing a quinone
      cofactor. It is encoded by an operon with two genes lodA and lodB. The first one
      codes for the oxidase, while the second one encodes a protein required for the
      expression of the former. Genome sequencing of M. mediterranea has revealed that
      it contains two additional operons encoding proteins with sequence similarity to
      LodA. In this study, it is shown that the product of one of such genes,
      Marme_1655, encodes a protein with glycine oxidase activity. This activity shows
      important differences in terms of substrate range and sensitivity to inhibitors
      to other glycine oxidases previously described which are flavoproteins
      synthesized by Bacillus. The results presented in this study indicate that the
      products of the genes with different degrees of similarity to lodA detected in
      bacterial genomes could constitute a reservoir of different oxidases. 

PMID- 23873698
TI  - Design and Synthesis of a gamma(1)beta(8)-Cyclodextrin Oligomer: A New Platform
      with Potential Application as a Dendrimeric Multicarrier.
AB  - We report the synthesis and characterization of a water-soluble, star-shaped
      macromolecular platform consisting of eight beta-cyclodextrin (beta-CD) units
      anchored to the narrower rim of a gamma-CD core through bis(triazolyl)alkyl
      spacers. The efficient synthetic protocol is based on the microwave (MW)-promoted
      Cu-catalyzed 1,3-dipolar cycloaddition of CD monoazides to CD monoacetylenes. The
      ligand-hosting capability of the construct has been assessed by relaxometric
      titration and nuclear magnetic relaxation dispersion (NMRD) profiling, which
      showed it to be good, and this was supported by molecular dynamics simulations.
      To demonstrate the feasibility of obtaining supramolecular structures with high
      hosting ability, we designed a dimeric platform, formed by joining two nonamers
      through the gamma-CD cores through a bis(lithocholic acid) linker. With a view to
      the potential biological applications, cytotoxicity and extent of binding to
      human serum albumin were assessed. The properties of this dendrimeric
      multicarrier make it suitable for pharmaceutical and diagnostic purposes, ranging
      from targeted drug delivery to molecular imaging. 

PMID- 23873699
TI  - Trabecular bone score (TBS) predicts vertebral fractures in Japanese women over
      10 years independently of bone density and prevalent vertebral deformity: the
      Japanese Population-Based Osteoporosis (JPOS) cohort study.
AB  - Bone strength is predominantly determined by bone density, but bone
      microarchitecture also plays an important role. We examined whether trabecular
      bone score (TBS) predicts the risk of vertebral fractures in a Japanese female
      cohort. Of 1950 randomly selected women aged 15 to 79 years, we analyzed data
      from 665 women aged 50 years and older, who completed the baseline study and at
      least one follow-up survey over 10 years, and who had no conditions affecting
      bone metabolism. Each survey included spinal imaging by dual-energy X-ray
      absorptiometry (DXA) for vertebral fracture assessment and spine areal bone
      mineral density (aBMD) measurement. TBS was obtained from spine DXA scans
      archived in the baseline study. Incident vertebral fracture was determined when
      vertebral height was reduced by 20% or more and satisfied McCloskey-Kanis
      criteria or Genant's grade 2 fracture at follow-up. Among eligible women (mean
      age 64.1 +/- 8.1 years), 92 suffered incident vertebral fractures (16.7/10(3)
      person-years). These women were older with lower aBMD and TBS values relative to
      those without fractures. The unadjusted odds ratio of vertebral fractures for one
      standard deviation decrease in TBS was 1.98 (95% confidence interval [CI] 1.56,
      2.51) and remained significant (1.64, 95% CI 1.25, 2.15) after adjusting for
      aBMD. The area under the receiver operating characteristic curve of TBS and aBMD
      combined was 0.700 for vertebral fracture prediction and was not significantly
      greater than that of aBMD alone (0.673). However, reclassification improvement
      measures indicated that TBS and aBMD combined significantly improved risk
      prediction accuracy compared with aBMD alone. Further inclusion of age and
      prevalent vertebral deformity in the model improved vertebral fracture
      prediction, and TBS remained significant in the model. Thus, lower TBS was
      associated with higher risk of vertebral fracture over 10 years independently of
      aBMD and clinical risk factors including prevalent vertebral deformity. TBS could
      effectively improve fracture risk assessment in clinical settings.

PMID- 23873700
TI  - Novel cytotoxic exhibition mode of antimicrobial peptide anoplin in MEL cells,
      the cell line of murine Friend leukemia virus-induced leukemic cells.
AB  - Anoplin is a recently discovered antimicrobial peptide (AMP) isolated from the
      venom sac of the spider wasp Anoplius samariensis, and it is one of the shortest
      alpha-helical AMP found naturally to date consisting of only ten amino acids.
      Previous results showed that anoplin exhibits potent antimicrobial activity but
      little hemolytic activity. In this study, we synthesized anoplin, studied its
      cytotoxicity in Friend virus-induced leukemia cells [murine erythroleukemia (MEL)
      cells], and proposed its possible mechanism. Our results showed that anoplin
      could inhibit the proliferation of MEL cells in a dose-dependent and time
      dependent manner via disrupting the integrity of cell membrane, which indicated
      that anoplin exerts its cytotoxicity efficacy. In addition, the cell cycle
      distribution of MEL cells was arrested in the G0/G1 phase significantly. However,
      anoplin could not induce obvious apoptosis in MEL cells, as well as anoplin could
      not induce visible changes on morphology and quantity in the bone marrow cells
      isolated from normal mice. All of these results indicate that anoplin, as
      generally believed, is a selective AMP, a value characteristic in the design of
      safe therapeutic agents. The cytotoxicity of anoplin on MEL cells was mainly
      attributable to the plasma membrane perturbation and also to the intracellular
      events such as the arrest of cell cycle. Although this is an initial study that
      explored the activity of anoplin in vitro rather than in vivo, with the
      increasing resistance of conventional chemotherapy, there is no doubt that
      anoplin has desirable feature to be developed as a novel and selective anticancer
      agent.

PMID- 23873701
TI  - BMI1, the polycomb-group gene, is recurrently targeted by genomic rearrangements
      in progressive B-cell leukemia/lymphoma.
AB  - BMI1, a Polycomb-group gene located at 10p12.2, is implicated in the pathogenesis
      of a variety of tumors. However, the genetic molecular mechanisms underlying its
      aberrant expression in cancer cells remain largely unknown. In this study, we
      show that BMI1 is recurrently targeted by chromosomal aberrations in B-cell
      leukemia/lymphoma. We identified a novel t(10;14)(p12;q32)/IGH-BMI1 rearrangement
      and its IGL variant in six cases of chronic lymphocytic leukemia (CLL) and found
      that these aberrations were consistently acquired at time of disease progression
      and high grade transformation of leukemia (Richter syndrome). The IG-BMI1
      translocations were not associated with any particular molecular subtype of CLL
      and the leukemias were negative for common mutations of NOTCH1 and TP53, known to
      increase a risk of progression and transformation in CLL. In addition, using FISH
      and SNP array analysis, we identified a wide range of BMI1-involving 10p12
      lesions in 17 cases of mantle cell lymphoma (MCL). These aberrations included
      various balanced and unbalanced structural abnormalities and very frequently but
      not exclusively, were associated with gain of the BMI1 locus and loss of the 10p
      terminal sequences. These findings point to genomic instability at the 10p region
      in MCL which likely promotes rearrangements and deregulation of BMI1. Our
      findings are in line with previously published observations correlating
      overexpression of BMI1 with tumor progression and chemoresistance. In summary,
      our study provides new insights into genetic molecular mechanisms underlying
      aberrant expression of BMI1 in lymphoma and documents its contribution in the
      pathogenesis of Richter syndrome and MCL.

PMID- 23873702
TI  - A protocol to evaluate one electron redox potential for iron complexes.
AB  - Density functional theory calculation has been performed to calculate the redox
      potential and the correct ground spin state of iron complexes in acetonitrile.
      Widely used B3LYP functional is applied with the spin state corrected basis sets.
      The newly developed protocol for the set of 21 iron complexes is to optimize the
      structure at the level of the B3LYP/6-31G* and to calculate the single point
      electronic energy with the same functional and the modified basis sets s6-31G*
      for the iron atom and 6-31+G* for other ligand atoms. The solvation energy is
      considered through the polarized continuum model and the cavity creation energy
      is included for the accurate spin state description. Modifying the cavity size by
      employing the different scaling factor according to the mean absolute value of
      the natural population analysis charge (MA-NPA) is introduced. The molecule with
      the large MA-NPA requires the cavity size smaller than the less polar one. This
      protocol gives only 1 wrong ground spin state among the 18 iron complexes for
      which experimental data are known. For the open circuit voltage (OCV)
      calculation, our protocol performs well yielding the mean absolute error of 0.112
      V for the test set. The close correlation between the calculated and the
      experimental OCV are obtained.

PMID- 23873703
TI  - Perception of pulmonary function and asthma control: the differential role of
      child versus caregiver anxiety and depression.
AB  - OBJECTIVE: To examine child and caregiver anxiety and depression as predictors of
      children's perception of pulmonary function, quick-relief medication use, and
      pulmonary function. METHOD: 97 children with asthma, ages 7 to 11 years old,
      reported their anxiety and depressive symptoms and completed spirometry.
      Caregivers completed a psychiatric interview. Children's predictions of their
      peak expiratory flow were compared with actual values across 6 weeks. Quick
      relief medication use was assessed by Dosers. RESULTS: Children's anxiety
      symptoms were associated with over-perception of respiratory compromise and
      greater quick-relief medication use. Children's depressive symptoms were
      associated with greater quick-relief medication use, but not perception of
      pulmonary function. Children of caregivers with an anxiety or depressive disorder
      had lower pulmonary function than children of caregivers without anxiety or
      depression. CONCLUSIONS: Child anxiety was associated with a subjective pattern
      of over-perception. Caregiver anxiety and depression were risk factors for lower
      lung function assessed by objective measurement.

PMID- 23873704
TI  - MicroRNA expression profile and functional analysis reveal that miR-382 is a
      critical novel gene of alcohol addiction.
AB  - Alcohol addiction is a major social and health concern. Here, we determined the
      expression profile of microRNAs (miRNAs) in the nucleus accumbens (NAc) of rats
      treated with alcohol. The results suggest that multiple miRNAs were aberrantly
      expressed in rat NAc after alcohol injection. Among them, miR-382 was down
      regulated in alcohol-treated rats. In both cultured neuronal cells in vitro and
      in the NAc in vivo, we identified that the dopamine receptor D1 (Drd1) is a
      direct target gene of miR-382. Via this target gene, miR-382 strongly modulated
      the expression of DeltaFosB. Moreover, overexpression of miR-382 significantly
      attenuated alcohol-induced up-regulation of DRD1 and DeltaFosB, decreased
      voluntary intake of and preference for alcohol and inhibited the DRD1-induced
      action potential responses. The results indicated that miRNAs are involved in and
      may represent novel therapeutic targets for alcoholism. 

PMID- 23873706
TI  - Enantioselective uptake and translocation of a novel chiral neonicotinoid
      insecticide cycloxaprid in Youdonger (Brassica campestris subsp. Chinensis).
AB  - For a novel potential commercial chiral pesticide, an independent study on the
      fate characteristics and residues of each stereoisomer is essential if the
      application rates for the pesticide and human exposure are to be reduced. The
      absorption and translocation behavior of a chiral insecticide, cycloxaprid, in
      plants treated by root immersion and blade smearing was studied using (14)C
      labeling tracer techniques. With the root treatment, total absorption of (1R;8S)
      cycloxaprid (RS) (12.39%) was much greater than that of (1S;8R)-cycloxaprid (SR)
      (3.31%) at 192 h after treatment (HAT). The mass concentrations (RS/SR) of
      cycloxaprid in the roots, cotyledons, leaf 1, leaf 2, and leaf 3 were 37.0/16.8,
      8.3/2.8, 11.7/6.5, 5.1/4.8, and 8.0/4.7 mg kg(-1) (fresh weight), respectively,
      at 192 HAT at an initial concentration 1.6 mg kg(-1). With the foliar application
      treatment, no significant difference was observed between the total absorption of
      RS (3.11%) and SR (4.03%) at the end of the treatment. Both acropetal and
      basipetal transport of absorbed (14)C occurred and more than 71.83% of absorbed
      RS and 82.42% of SR remained in the treated leaf. Stereoselective absorption was
      observed during root uptake but not during foliar absorption.

PMID- 23873705
TI  - Transcriptomic and phenotypic analysis of paralogous spx gene function in
      Bacillus anthracis Sterne.
AB  - Spx of Bacillus subtilis is a redox-sensitive protein, which, under disulfide
      stress, interacts with RNA polymerase to activate genes required for maintaining
      thiol homeostasis. Spx orthologs are highly conserved among low %GC Gram-positive
      bacteria, and often exist in multiple paralogous forms. In this study, we used B.
      anthracis Sterne, which harbors two paralogous spx genes, spxA1 and spxA2, to
      examine the phenotypes of spx null mutations and to identify the genes regulated
      by each Spx paralog. Cells devoid of spxA1 were sensitive to diamide and hydrogen
      peroxide, while the spxA1 spoxA2 double mutant was hypersensitive to the thiol
      specific oxidant, diamide. Bacillus anthracis Sterne strains expressing spxA1DD
      or spxA2DD alleles encoding protease-resistant products were used in microarray
      and quantitative real-time polymerase chain reaction (RT-qPCR) analyses in order
      to uncover genes under SpxA1, SpxA2, or SpxA1/SpxA2 control. Comparison of
      transcriptomes identified many genes that were upregulated when either SpxA1DD or
      SpxA2DD was produced, but several genes were uncovered whose transcript levels
      increased in only one of the two SpxADD-expression strains, suggesting that each
      Spx paralog governs a unique regulon. Among genes that were upregulated were
      those encoding orthologs of proteins that are specifically involved in
      maintaining intracellular thiol homeostasis or alleviating oxidative stress. Some
      of these genes have important roles in B. anthracis pathogenesis, and a large
      number of upregulated hypothetical genes have no homology outside of the B.
      cereus/thuringiensis group. Microarray and RT-qPCR analyses also unveiled a
      regulatory link that exists between the two spx paralogous genes. The data
      indicate that spxA1 and spxA2 are transcriptional regulators involved in
      relieving disulfide stress but also control a set of genes whose products
      function in other cellular processes.

PMID- 23873707
TI  - Adjusting for reporting delay in cancer incidence when combining different sets
      of cancer registries.
AB  - Cancer registries collect cancer incidence data that can be used to calculate
      incidence rates in a population and track changes over time. For incidence rates
      to be accurate, it is critical that diagnosed cases be reported in a timely
      manner. Registries typically allow a fixed amount of time (e.g. two years) for
      diagnosed cases to be reported before releasing the initial case counts for a
      particular diagnosis year. Inevitably, however, additional cases are reported
      after the initial counts are released; these extra cases are included in
      subsequent releases that become more complete over time, while incidence rates
      based on earlier releases will underestimate the true rates. Statistical methods
      have been developed to estimate the distribution of reporting delay (the amount
      of time until a diagnosed case is reported) and to correct incidence rates for
      underestimation due to reporting delay. Since the observed reporting delays must
      be less than the length of time the registry has been collecting data, most
      methods estimate a truncated delay distribution. These methods can be applied to
      a group of registries that began collecting data in the same diagnosis year. In
      this paper, we extend the methods to two groups of registries that began
      collecting data in two different diagnosis years (so that the delay distributions
      are truncated at different times). We apply the proposed method to data from the
      National Cancer Institute's Surveillance Epidemiology and End Results (SEER)
      program, a consortium of U.S. cancer registries that includes nine registries
      with data collection beginning in 1981 and four registries with data collection
      beginning in 1992. We use the method to obtain delay-adjusted incidence rates for
      melanoma, liver cancer, and Hodgkin lymphoma. 

PMID- 23873708
TI  - Exploring critical determinants of protein amyloidogenesis: a review.
AB  - The transformation of polypeptide chains from their globular native structure to
      fibrillar aggregates has been a matter of great concern because of the
      involvement of these aggregates in the onset of several degenerative diseases.
      These aggregates exhibit highly ordered cross beta sheet structures and are known
      as 'amyloids'. Formation of amyloids in the body is associated with cytotoxicity
      due to direct interaction of the aggregated species with the cell membrane
      leading to cellular permeability or due to loss of functionality of the proteins
      involved in the amyloid formation. The preference of polypeptide chains to remain
      in their native conformation or to aggregate into amyloids is guided by several
      factors such as its conformation at specific condition, concentration,
      physicochemical properties of the amino acid sequence and so on. In the current
      review, we have reviewed the different factors that guide the transition of
      proteins from their natively folded state to the amyloidogenic state.
      Understanding the critical determinants of amyloidogenesis is vital towards
      deciphering the molecular mechanism of amyloidogenesis and for the development of
      effective therapeutics against amyloidosis.

PMID- 23873710
TI  - Dehydrogenative boron homocoupling of an amine-borane.

PMID- 23873709
TI  - Project BOOST: effectiveness of a multihospital effort to reduce
      rehospitalization.
AB  - BACKGROUND: Rehospitalization is a prominent target for healthcare quality
      improvement and performance-based reimbursement. The generalizability of existing
      evidence on best practices is unknown. OBJECTIVE: To determine the effect of
      Project BOOST (Better Outcomes for Older adults through Safe Transitions) on
      rehospitalization rates and length of stay. DESIGN: Semicontrolled pre-post
      study. SETTING/PARTICIPANTS: Volunteer sample of 11 hospitals varying in
      geography, size, and academic affiliation. INTERVENTION: Hospitals implemented
      Project BOOST-recommended tools supported by an external quality improvement
      physician mentor. METHODS: Pre-post changes in readmission rates and length of
      stay within BOOST units, and between BOOST units and site-designated control
      units. RESULTS: The average rate of 30-day rehospitalization in BOOST units was
      14.7% prior to implementation and 12.7% 12 months later (P = 0.010), reflecting
      an absolute reduction of 2% and a relative reduction of 13.6%. Rehospitalization
      rates for matched control units were 14.0% in the preintervention period and
      14.1% in the postintervention period (P = 0.831). The mean absolute reduction in
      readmission rates in BOOST units compared to control units was 2.0% (P = 0.054
      for signed rank test comparing differences in readmission rate reduction in BOOST
      units compared to site-matched control units). CONCLUSIONS: Participation in
      Project BOOST appeared to be associated with a decrease in readmission rates.

PMID- 23873711
TI  - Cognitive-affective symptoms of depression after myocardial infarction: different
      prognostic importance across age groups.
AB  - OBJECTIVE: Cognitive-affective symptoms of depression may not be as strongly
      related to prognosis after myocardial infarction (MI) as somatic depressive
      symptoms. Because it is not known whether this pattern of results is influenced
      by the age at which patients are diagnosed as having MI, we examined whether the
      importance of these symptoms is age dependent in the Enhancing Recovery in
      Coronary Heart Disease study. METHODS: Patients with depression after MI (n =
      1823) in the Enhancing Recovery in Coronary Heart Disease study were stratified
      into the following age groups: younger than 70 years (mean [standard deviation] =
      55 [9.0] years) and 70 years or older (mean [standard deviation] = 76 [4.9]
      years). Measurements included demographic and clinical data and the Beck
      Depression Inventory. The end point was a composite of recurrent MI and mortality
      during a mean follow-up of 2.1 years. RESULTS: Patients 70 years or older had
      more severe manifestations of cardiac disease and somatic comorbidities than did
      patients younger than 70 years (p < .001). During follow-up, 456 patients died or
      had a recurrent MI. In patients 70 years or older, increasing age, disease
      severity, and comorbidities--but not depressive symptoms--independently predicted
      prognosis. In contrast, cognitive-affective symptoms of depression predicted
      death/MI in patients younger than 70 years (hazard ratio = 1.03, 95% confidence
      interval = 1.01-1.04, p = .011), after adjustment for disease severity and
      comorbidities. Somatic symptoms largely explained the link between cognitive
      affective symptoms and adverse events, with the exception of hopelessness (hazard
      ratio = 1.47, 95% confidence interval = 1.11-1.95, p = .007), suggesting that
      somatic depressive symptoms accurately reflect the depressed mood state in this
      age group. CONCLUSIONS: Somatic symptoms and hopelessness independently predicted
      death/MI in MI patients younger than 70 years. Research needs to reexamine the
      modulating effect of age in studies on somatic and cognitive-affective symptoms
      of post-MI depression.

PMID- 23873712
TI  - Sleep problems and cardiovascular function in children.
AB  - OBJECTIVE: To assess the associations of sleep problems with 24-hour ambulatory
      blood pressure and cardiovascular reactivity in children. METHODS: Sleep problems
      in 285 term-born, healthy 8-year-olds (mean [standard deviation] = 8.1 [0.3]
      years) were measured with a parent-rated Sleep Disturbance Scale for Children.
      Ambulatory blood pressure (n = 241) was measured for 24 hours (41% nonschool
      days) with an oscillometric device. The children (n = 274) underwent the Trier
      Social Stress Test for Children during which blood pressure, electrocardiography,
      and thoracic impedance were recorded and processed offline to give measures of
      cardiovascular and autonomic function. RESULTS: No associations were found
      between sleep problems and 24-hour ambulatory blood pressure. Children with sleep
      breathing disorders (n = 5) had higher baseline sympathetic vascular activity (p
      = .014) and higher heart rate (p = .044) and sympathetic cardiac activity (p =
      .031) in reaction to stress. Children with disorders of excessive somnolence (n =
      55) had higher baseline parasympathetic activity (p = .016). None of the
      associations remained significant after controlling for multiple testing.
      CONCLUSIONS: Our results suggest that in a healthy community sample of
      prepubertal children, sleep problems are not associated with an unhealthy
      cardiovascular phenotype at this age. However, associations may be underestimated
      because of the low prevalence of sleep breathing disorders in this sample and may
      not generalize to older populations.

PMID- 23873715
TI  - Cascade- and orthoamide-type Overman rearrangements of allylic vicinal diols.
AB  - This article describes the details of two new types of Overman rearrangement from
      allylic vicinal diols. Starting from identical diols, both bis(imidate)s and
      cyclic orthoamides were selectively synthesized by simply changing the reaction
      conditions. Whilst exposure of the bis(imidate)s to thermal conditions initiated
      the double Overman rearrangement to introduce two identical nitrogen groups in a
      single operation (the cascade-type Overman rearrangement), the reaction of cyclic
      orthoamides resulted in a single rearrangement (the orthoamide-type Overman
      rearrangement). The newly generated allylic alcohols from the orthoamide-type
      reaction can potentially undergo a variety of further transformations. For
      instance, we demonstrated an Overman/Claisen sequence in one pot. The most
      conspicuous feature of this method is that it offers precise control over the
      number of Overman rearrangements from the same allylic vicinal diols. This method
      also excludes the tedious protecting-group manipulations of the homoallylic
      alcohols, which are necessary in conventional Overman rearrangements. All of the
      performed rearrangements proceeded in a completely diastereoselective fashion
      through a chair-like transition state. 

PMID- 23873713
TI  - Stress-induced inflammatory responses in women: effects of race and pregnancy.
AB  - OBJECTIVE: African Americans experience preterm birth at nearly twice the rate of
      whites. Chronic stress associated with minority status is implicated in this
      disparity. Inflammation is a key biological pathway by which stress may affect
      birth outcomes. This study examined the effects of race and pregnancy on stress
      induced inflammatory responses. METHODS: Thirty-nine women in the second
      trimester of pregnancy (19 African American, 20 white) and 39 demographically
      similar nonpregnant women completed an acute stressor (Trier Social Stress Test).
      Psychosocial characteristics, health behaviors, and affective responses were
      assessed. Serum interleukin (IL)-6 was measured at baseline, 45 minutes, and 120
      minutes poststressor. RESULTS: IL-6 responses at 120 minutes poststressor were
      46% higher in African Americans versus whites (95% confidence interval = 8%-81%,
      t(72) = 3.51, p = .001). This effect was present in pregnancy and nonpregnancy.
      IL-6 responses at 120 minutes poststressor tended to be lower (15%) in pregnant
      versus nonpregnant women (95% confidence interval = -5%-32%, p = .14). Racial
      differences in inflammatory responses were not accounted for by demographics,
      psychological characteristics, health behaviors, or differences in salivary
      cortisol. Pregnant whites showed lower negative affective responses than did
      nonpregnant women of either race (p values <= .007). CONCLUSIONS: This study
      provides novel evidence that stress-induced inflammatory responses are more
      robust among African American women versus whites during pregnancy and
      nonpregnancy. The ultimate impact of stress on health is a function of stressor
      exposure and physiological responses. Individual differences in stress-induced
      inflammatory responses represent a clear target for continued research efforts in
      racial disparities in health during pregnancy and nonpregnancy.

PMID- 23873714
TI  - The interactive effects of cerebral perfusion and depression on cognitive
      function in older adults with heart failure.
AB  - OBJECTIVE: Depression is common among persons with heart failure (HF) and has
      been linked to cognitive impairment in this population. The mechanisms of this
      relationship are unclear, and the current study examined whether cerebral
      perfusion moderates the association between depressive symptoms and cognitive
      impairment in patients with HF. METHODS: Persons with HF (n = 89; mean [standard
      deviation] age = 67.61 [11.78] years) completed neuropsychological testing and
      impedance cardiography. Depressive symptoms were assessed using the Beck
      Depression Inventory II, and transcranial Doppler was used to quantify cerebral
      perfusion. RESULTS: Depression was associated with reduced performance on tasks
      assessing attention/executive function (r = -0.28), language (r = -0.0.30), and
      motor function (r = -0.28) in unadjusted models (p values <.05). Global cerebral
      blood flow was correlated with memory performance (r = 0.22, p = .040) but not
      with other tasks. A moderation analysis was performed using hierarchical
      regression models for attention/executive function, memory, language, and motor
      function. For each model, medical and demographic characteristics were entered
      into the initial blocks, and the final block consisted of an interaction term
      between global cerebral blood flow velocity and the Beck Depression Inventory II.
      The interaction between greater depressive symptoms and decreased global cerebral
      blood flow velocity was associated with greater deficits in attention/executive
      function (beta = .32, DeltaR(2) = 0.08, p = .003). CONCLUSIONS: Depressive
      symptoms and cerebral hypoperfusion interact to adversely affect cognitive
      performance in older adults with HF. Longitudinal studies are needed to clarify
      this relationship and elucidate subsequent neuropathology.

PMID- 23873716
TI  - Biomarkers of cardiovascular stress and incident chronic kidney disease.
AB  - BACKGROUND: Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and
      high-sensitivity troponin I (hsTnI) are emerging predictors of adverse clinical
      outcomes. We examined whether circulating concentrations are related to the
      development of kidney disease in the community. METHODS: Plasma GDF-15, sST2, and
      hsTnI concentrations were measured in 2614 Framingham Offspring cohort
      participants (mean age 57 years, 54% women) at the sixth examination cycle (1995
      1998). Associations of biomarkers with incident chronic kidney disease [CKD, eGFR
      <60 mL . min(-1) . (1.73 m(2)) (-1), n = 276], microalbuminuria (urinary albumin
      to creatinine ratio >=25 mg/g in women and 17 mg/g in men, n = 191), and rapid
      decline in renal function [decline in eGFR >=3 mL . min(-1) . (1.73 m(2)) (-1)
      per year, n = 237], were evaluated using multivariable logistic regression; P <
      0.006 was considered statistically significant in primary analyses. RESULTS:
      Participants were followed over a mean of 9.5 years. Higher plasma GDF-15 was
      associated with incident CKD [multivariable-adjusted odds ratio (OR) 1.9 per 1-U
      increase in log-GDF-15, 95% CI 1.6-2.3, P < 0.0001] and rapid decline in renal
      function (OR, 1.6; 95% CI, 1.3-1.8; P < 0.0001). GDF-15, sST2, and hsTnI had
      suggestive associations with incident microalbuminuria but did not meet the
      prespecified P-value threshold after multivariable adjustment. Adding plasma GDF
      15 to clinical covariates improved risk prediction of incident CKD: the c
      statistic increased from 0.826 to 0.845 (P = 0.0007), and categorical net
      reclassification was 6.3% (95% CI, 2.7-9.9%). CONCLUSIONS: Higher circulating GDF
      15 is associated with incident renal outcomes and improves risk prediction of
      incident CKD. These findings may provide insights into the mechanisms of renal
      injury.

PMID- 23873718
TI  - Moving beyond the national lung screening trial: discussing strategies for
      implementation of lung cancer screening programs.
AB  - The National Lung Screening Trial (NLST) has sparked new interest in the adoption
      of lung cancer screening using low-dose computed tomography (LDCT). If adopted at
      a national level, LDCT screening may prevent approximately 18,000 lung cancer
      deaths per year, potentially constituting a high-value public health
      intervention. Before incorporating LDCT screening into practice, health care
      institutions need to consider the risks associated with LDCT screening and the
      impact of LDCT screening on health care costs, as well as other remaining areas
      of uncertainty, including the unknown cost-effectiveness of LDCT screening. This
      article will review the benefits and risks of LDCT screening in light of the
      results of the NLST and other randomized trials, it will discuss the additional
      health care costs associated with LDCT screening from the perspective of health
      care payers, and it will examine the published cost-effectiveness analyses of
      LDCT screening. A subsequent discussion highlights guideline recommendations for
      implementation strategies, the goals of which are to ensure that those eligible
      for LDCT screening derive the benefits while minimizing the risks of screening
      and avoiding an unnecessary escalation in screening-related costs. The article
      concludes by endorsing the use of LDCT screening in institutions capable of
      responsible implementation of screening in both medical and economic terms. The
      key elements of responsible implementation include the development of
      standardized screening practices, careful selection of screening candidates, and
      the creation of prospective registries that will mitigate current areas of
      uncertainty regarding LDCT screening. 

PMID- 23873717
TI  - Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23
      in normal and ADHR mice.
AB  - Fibroblast growth factor 23 (FGF23) gain of function mutations can lead to
      autosomal dominant hypophosphatemic rickets (ADHR) disease onset at birth, or
      delayed onset following puberty or pregnancy. We previously demonstrated that the
      combination of iron deficiency and a knock-in R176Q FGF23 mutation in mature mice
      induced FGF23 expression and hypophosphatemia that paralleled the late-onset ADHR
      phenotype. Because anemia in pregnancy and in premature infants is common, the
      goal of this study was to test whether iron deficiency alters phosphate handling
      in neonatal life. Wild-type (WT) and ADHR female breeder mice were provided
      control or iron-deficient diets during pregnancy and nursing. Iron-deficient
      breeders were also made iron replete. Iron-deficient WT and ADHR pups were
      hypophosphatemic, with ADHR pups having significantly lower serum phosphate (p <
      0.01) and widened growth plates. Both genotypes increased bone FGF23 mRNA (>50
      fold; p < 0.01). WT and ADHR pups receiving low iron had elevated intact serum
      FGF23; ADHR mice were affected to a greater degree (p < 0.01). Iron-deficient
      mice also showed increased Cyp24a1 and reduced Cyp27b1, and low serum 1,25
      dihydroxyvitamin D (1,25D). Iron repletion normalized most abnormalities. Because
      iron deficiency can induce tissue hypoxia, oxygen deprivation was tested as a
      regulator of FGF23, and was shown to stimulate FGF23 mRNA in vitro and serum C
      terminal FGF23 in normal rats in vivo. These studies demonstrate that FGF23 is
      modulated by iron status in young WT and ADHR mice and that hypoxia independently
      controls FGF23 expression in situations of normal iron. Therefore, disturbed iron
      and oxygen metabolism in neonatal life may have important effects on skeletal
      function and structure through FGF23 activity on phosphate regulation.

PMID- 23873719
TI  - Circulating tumor cells following first chemotherapy cycle: an early and strong
      predictor of outcome in patients with metastatic breast cancer.
AB  - We investigated the prognostic significance of circulating tumor cells (CTCs)
      determined immediately before the second cycle of chemotherapy in patients with
      metastatic breast cancer (MBC). The CTC counts were taken at baseline, before the
      first cycle of chemotherapy (CTC-0), and on day 21 before commencing the second
      cycle of chemotherapy (CTC-21) in consecutive MBC patients. The study's primary
      objectives were to analyze relationships between CTC-21 count and overall
      survival (OS). Based on the current literature, the CTC measurements were
      dichotomized as 0-4 versus >= 5 CTCs. Of 117 patients recruited, 99 were
      evaluable. Patients with 0-4 CTCs on day 21 had a significantly better OS than
      those with >= 5 CTCs (median OS: 38.5 months vs. 8.7 months). They also had a
      significantly better progression-free survival (PFS; median: 9.4 months vs. 3.0
      months) and clinical benefit rate (77% vs. 44%). The OS of patients whose
      baseline CTCs were >= 5 but dropped to <5 on day 21 was apparently similar to
      those who had <5 CTCs at baseline. In a Cox regression analysis, CTC-21 was the
      only independent variable significantly predicting OS and PFS. Our data indicate
      that CTCs determined immediately before the second cycle of chemotherapy is an
      early and strong predictor of treatment outcome in MBC patients.

PMID- 23873721
TI  - Ab initio study of the high-temperature phase transition in crystalline GeO2.
AB  - Germanium dioxide (GeO2 ) takes two forms at ambient pressure: a
      thermodynamically stable rutile-type structure and a high-temperature quartz-type
      polymorph. Here, we investigate the phase stability at finite temperatures by ab
      initio phonon and thermochemical computations. We use gradient-corrected density
      functional theory (PBE-GGA) and pay particular attention to the modeling of the
      "semicore" germanium 3d orbitals (ascribing them either to the core or to the
      valence region). The phase transition is predicted correctly in both cases, and
      computed heat capacities and entropies are in excellent agreement with
      thermochemical database values. Nonetheless, the computed formation energies of
      alpha-quartz-type GeO2 (and, consequently, the predicted transition temperatures)
      differ significantly depending on theoretical method. Remarkably, the simpler and
      cheaper computational approach produces seemingly better results, not worse. In
      our opinion, GeO2 is a nice test case that illustrates both possibilities and
      limitations of modern ab initio thermochemistry.

PMID- 23873720
TI  - RAS mutations in thyroid cancer.
AB  - In recent years, our understanding of the genetic alterations underlying thyroid
      oncogenesis has greatly expanded. The use of molecular markers, including RAS, in
      the management of thyroid carcinoma is also increasing. This review summarizes
      the current literature surrounding RAS and discusses its potential as a
      diagnostic and prognostic indicator in the management of thyroid cancer. 

PMID- 23873722
TI  - Honey bees, neonicotinoids and bee incident reports: the Canadian situation.
AB  - BACKGROUND: Neonicotinoid insecticides have been the target of much scrutiny as
      possible causes of recent declines observed in pollinator populations. Although
      neonicotinoids have been implicated in honey bee pesticide incidents, there has
      been little examination of incident report data. Here we summarize honey bee
      incident report data obtained from the Canadian Pest Management Regulatory Agency
      (PMRA). RESULTS: In Canada, there were very few honey bee incidents reported in
      2007-2011 and data were not collected prior to 2007. In 2012, a significant
      number of incidents were reported in the province of Ontario, where exposure to
      neonicotinoid dust during planting of corn was suspected to have caused the
      incident in up to 70% of cases. Most of these incidents were classified as
      'minor' by the PMRA, and only six cases were considered 'moderate' or 'major'. In
      that same year, there were over three times as many moderate or major incidents
      due to older non-neonicotinoid pesticides, involving numbers of hives or bees far
      greater than the number of moderate or major incidents suspected to be due to
      neonicotinoid poisoning. CONCLUSIONS: These data emphasize that, while exposure
      of honey bees to neonicotinoid-contaminated dust during corn planting needs to be
      mitigated, other pesticides also pose a risk.

PMID- 23873723
TI  - Immunity and immune response, pathology and pathologic changes: progress and
      challenges in the immunopathology of yellow fever.
AB  - Yellow fever is a viral hemorrhagic fever, which affects people living in Africa
      and South America and is caused by the yellow fever virus, the prototype species
      in the Flavivirus genus (Flaviviridae family). Yellow fever virus infection can
      produce a wide spectrum of symptoms, ranging from asymptomatic infection or
      oligosymptomatic illness to severe disease with a high fatality rate. In this
      review, we focus in the mechanisms associated with the physiopathology of yellow
      fever in humans and animal models. It has been demonstrated that several factors
      play a role in the pathological outcome of the severe form of the disease
      including direct viral cytopathic effect, necrosis and apoptosis of hepatocyte
      cells in the midzone, and a minimal inflammatory response as well as low-flow
      hypoxia and cytokine overproduction. New information has filled several gaps in
      the understanding of yellow fever pathogenesis and helped comprehend the course
      of illness. Finally, we discuss prospects for an immune therapy in the light of
      new immunologic, viral, and pathologic tools.

PMID- 23873724
TI  - Probing the S1' site for the identification of non-zinc-binding MMP-2 inhibitors.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in several
      pathological states. Among them, MMP-2 is a relevant therapeutic target because
      of its role in cancer development and progression. Many MMP inhibitors (MMPIs)
      have been discovered over the last 30 years, and the majority of them contain a
      functional group that binds the zinc ion (zinc-binding group; ZBG).
      Unfortunately, no MMPIs have reached the market yet, owing to toxic effects due
      to unselective interactions of the ZBG. The new generation of MMPIs that do not
      bind the zinc ion could overcome problems of selectivity and toxicity, but have
      so far been developed only for MMP-8, -12, and -13. In this work, a virtual
      screening protocol was established by combining ligand- and structure-based
      methods to identify non-zinc-binding MMP-2 inhibitors using a new-generation MMP
      8 inhibitor as a probe to find unexplored interactions in the MMP-2 S1' site. The
      screening allowed the identification of micromolar MMP-2 inhibitors that
      putatively avoid binding the zinc ion, as demonstrated by docking calculations.
      The LIA model, built to correlate predicted and experimental binding energies of
      the identified non-zinc-binding MMP-2 hits, underpins the reliability of the
      predicted docking poses. 

PMID- 23873725
TI  - N-methyl-D-aspartate receptors strongly regulate postsynaptic activity levels
      during optic nerve regeneration.
AB  - During development, neuronal activity is used as a cue to guide synaptic
      rearrangements to refine connections. Many studies, especially in the visual
      system, have shown that the N-methyl-D-aspartate receptor (NMDAr) plays a key
      role in mediating activity-dependent refinement through long-term potentiation
      (LTP)-like processes. Adult goldfish can regenerate their optic nerve and utilize
      neuronal activity to generate precise topography in their projection onto tectum.
      Although the NMDAr has been implicated in this process, its precise role in
      regeneration has not been extensively studied. In examining NMDAr function during
      regeneration, we found salient differences compared with development. By using
      field excitatory postsynaptic potential (fEPSP) recordings, the contribution of
      the NMDAr at the primary optic synapse was measured. In contrast to development,
      no increase in NMDAr function was detectable during synaptic refinement. Unlike
      development, LTP could not be reliably elicited during regeneration.
      Unexpectedly, we found that NMDAr exerted a major effect on regulating ongoing
      tectal (postsynaptic) activity levels during regeneration. Blocking NMDAr
      strongly suppressed spontaneous activity during regeneration but had no
      significant effect in the normal projection. This difference could be attributed
      to an occlusion effect of strong optic drive in the normal projection, which
      dominated ongoing tectal activity. During regeneration, this optic drive is
      largely absent. Optic nerve stimulation further indicated that the NMDAr had
      little effect on the ability of optic fibers to evoke early postsynaptic impulse
      activity but was important for late network activity. These results indicate
      that, during regeneration, the NMDAr may play a critical role in the homeostatic
      regulation of ongoing activity and network excitability.

PMID- 23873726
TI  - Stereoselective toxicity and metabolism of lactofen in primary hepatocytes from
      rat.
AB  - The stereoselective metabolism of lactofen in primary rat hepatocytes was studied
      using a chiral high-performance liquid chromatographic (HPLC) method. Rac
      lactofen and its two enantiomers, S-(+)- and R-(-)-lactofen, as well as two of
      its major metabolites, acifluorfen, S-(+)- and R-(-)-desethyl lactofen, were used
      as substrates,. The single and joint cytotoxicity of parent compounds and the
      metabolites were assessed by coincubation with rat hepatocytes as target cells.
      Cytotoxicity was determined by the methyl tetrazolium (MTT) assay. In hepatocyte
      incubations, S-(+)-lactofen was degraded more rapidly than R-(-)-lactofen, and a
      stereospecific formation of S-(+)-desethyl lactofen was detected. Metabolism of
      lactofen to desethyl lactofen was processed with the retention of configuration,
      and the achiral compound, acifluorfen, was the shared metabolite generated from
      both S-(+)- and R-(-)-lactofen. There was no chiral conversion of lactofen or
      desethyl lactofen enantiomers during the incubation. For the cytotoxicity
      research, the calculated EC50 values indicated that when being applied
      individually, the parent compound was less toxic than its metabolites, while the
      combination with metabolites enhanced its cytotoxic effects. The data presented
      here would be helpful for a more comprehensive assessment of the ecotoxicological
      and environmental risks of lactofen.

PMID- 23873727
TI  - Novel molecular correlates of endocannabinoid-mediated fear-conditioned analgesia
      in rats.
AB  - BACKGROUND: Fear-conditioned analgesia (FCA) is the profound suppression of pain
      during exposure to conditioned aversive stimuli and is mediated at spinal and
      supraspinal levels. The endocannabinoid system plays a key role in FCA. This
      study investigated brain and spinal cord expression of genes implicated in pain-
      and fear-related plasticity (Zif268 and Sgk1), following expression of formalin
      evoked nociception, contextual fear or endocannabinoid-mediated FCA. METHODS:
      Adult male Lister-Hooded rats received intra-plantar injection of formalin or
      saline, with or without administration of the CB1 receptor antagonist AM251 (3
      mg/kg, i.p.) or vehicle, 30 min prior to re-exposure to an arena paired 24 h
      previously with footshock. Real time quantitative polymerase chain reaction was
      used to measure expression of Zif268 and Sgk1 mRNA in the dorsal horn of the
      spinal cord (DHSC) and rostral ventromedial medulla (RVM) 30 min following arena
      re-exposure. RESULTS: Intra-plantar injection of formalin resulted in an increase
      in Zif268 and Sgk1 mRNA expression in the ipsilateral DHSC of non-fear
      conditioned rats, effects not observed in rats expressing FCA. Systemic
      administration of the CB1 receptor antagonist/inverse agonist AM251 attenuated
      both FCA and the FCA-associated suppression of Zif268 expression in the
      ipsilateral DHSC without affecting expression of Sgk1. Conditioned fear was
      associated with an increase in Zif268 mRNA expression in the RVM of saline-, but
      not formalin-treated rats. CONCLUSIONS: The present findings suggest that Zif268
      in the DHSC is an important molecular correlate of endocannabinoid-mediated FCA,
      and that fear-related expression of Zif268 in the RVM is influenced by the
      presence of nociceptive tone.

PMID- 23873728
TI  - Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight
      from the Keeping Warm in Later Life Project (KWILLT).
AB  - Nudges are interventions that aim to change people's behaviour through changing
      the environment in which they choose rather than appealing to their reasoning.
      Nudges have been proposed as of possible use in relation to health-related
      behaviour. However, nudges have been criticized as ethically dubious because they
      bypass peoples reasoning and (anyway) are of little help in relation to affecting
      ill-health that results from social determinants, such as poverty. Reducing the
      rate of excess winter deaths (EWDs) is a public health priority; however, EWD
      seems clearly to be socially determined such that nudges arguably have little
      role. This article defends two claims: (i) nudges could have a place in tackling
      even the heavily socially determined problem of EWD. We draw on evidence from an
      empirical study, the Keeping Warm in Later Life Project (KWILLT), to argue that
      in some cases the risk of cold is within the person's control to some extent such
      that environmental modifications to influence behaviour such as nudges are
      possible. (ii) Some uses of behavioural insights in the form of nudges are
      acceptable, including some in the area of EWD. We suggest a question-based
      framework by which to judge the ethical acceptability of nudges. 

PMID- 23873729
TI  - Direct four-electron reduction of O2 to H2O on TiO2 surfaces by pendant proton
      relay.

PMID- 23873730
TI  - Peptide matching between Epstein-Barr virus and human proteins.
AB  - Epstein-Barr virus proteins were examined for amino acid sequence matching to
      human proteins at the decapeptide level. We report that numerous EBV peptides of
      different length (from 10- to 13-mer) are present in 28 human proteins. The viral
      vs. human peptide overlap mainly involves the glycine-rich region allocated in
      the NH2 terminus of Epstein-Barr nuclear antigen 1 protein and host cellular
      components that play crucial roles in basic biochemical pathways, such as
      chromatin remodeling, RNA splicing, transmission across chemical/electrical
      synapses, and neurogenesis, and that, when altered, may characterize various
      pathologies such as immunodeficiency, systemic lupus erythematosus, myelination,
      and speech disorders. The present results might contribute to understand and
      define the (physio) pathological relationships and interactions occurring between
      EBV and the human host. 

PMID- 23873731
TI  - Tetraalkoxyphenanthrene-fused dehydroannulenes: synthesis, self-assembly, and
      electronic, optical, and electrochemical properties.
AB  - Novel tetraalkoxyphenanthrene-fused dehydro[12]-, [18]-, and [24]annulenes 1-3
      were synthesized by using Cu-mediated or Pd-catalyzed oxidative macrocyclization
      reactions as key steps, and their electronic, optical, and electrochemical
      properties have been investigated in detail. X-ray crystallographic analysis of a
      single crystal of 1 a demonstrated that the molecules were arranged
      longitudinally in a slipped pi-stacked fashion to form a 1D column. (1)H NMR and
      UV/Vis spectroscopic and cyclic voltammetric analysis in conjugation with nucleus
      independent chemical shift (NICS) calculations for 1-3 support that the
      annulation at the 9,10-positions of phenanthrene to the dehydroannulene ring
      enhances the tropicity and decreases the HOMO-LUMO gaps of the molecules relative
      to the benzannulation and that 1 possesses an antiaromatic character. Self
      association behavior due to pi-pi stacking in CDCl3 was observed for 1 and 2 and
      was quantified by concentration-dependent (1)H NMR spectroscopic measurements.
      The self-assembly of 1 and 2 into well-defined 1D superstructures with high
      aspect ratios were obtained, and the morphology and crystallinity of these
      compounds were investigated by means of SEM and wide-angle X-ray diffraction
      (WAXD) measurements. Furthermore, it was shown that 1 b and 2 b display liquid
      crystalline phases by means of differential scanning calorimetry, polarizing
      optical microscopy, and variable-temperature WAXD measurements.

PMID- 23873732
TI  - A primary care physician's ideal transitions of care--where's the evidence?
AB  - Reducing hospital readmissions is a national healthcare priority. Most of the
      interventions to reduce hospital readmission have been concentrated in the
      inpatient setting. However, there is increasing attention placed on the role of
      primary care physicians (PCPs) in improving the transition from hospital to home.
      In this article, a primary care physician's perspective of how inpatient and
      outpatient providers can partner to create the ideal care transition is
      described. Seven steps that occur during the hospitalization are highlighted:
      communicate with the PCP on admission, involve the PCP early regarding discharge
      planning, notify the PCP on hospital discharge, complete the discharge summary at
      time of discharge, schedule follow-up appointments by discharge, ensure
      prescriptions are available at the patient's pharmacy, and educate the patient
      about self-management. Another 7 are described as the role of the PCP and clinic
      staff: call the patient within 72 hours of discharge, ensure follow-up
      appointments with the PCP, coordinate care, repeat above until medically stable,
      create access for patients with new symptoms, track readmission rates, and track
      and review frequently admitted patients. Insights are offered on how the changing
      financial landscape can help support elements of this idealized transition-of
      care program.

PMID- 23873733
TI  - Mortality after lower extremity fractures in men with spinal cord injury.
AB  - In the United States, there are over 200,000 men with spinal cord injuries (SCIs)
      who are at risk for lower limb fractures. The risk of mortality after fractures
      in SCI is unknown. This was a population-based, cohort study of all male veterans
      (mean age 54.1; range, 20.3-100.5 years) with a traumatic SCI of at least 2
      years' duration enrolled in the Veterans Affairs (VA) Spinal Cord Dysfunction
      Registry from FY2002 to FY2010 to determine the association between lower
      extremity fractures and mortality. Mortality for up to 5 years was determined.
      The lower extremity fracture rate was 2.14 per 100 patient-years at risk for at
      least one fracture. In unadjusted models and in models adjusted for demographic,
      SCI-related factors, healthcare use, and comorbidities, there was a significant
      association between incident lower extremity fracture and increased mortality
      (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; HR, 1.36; 95%
      CI, 1.15-1.61, respectively). In complete SCI, the hazard of death after lower
      extremity fracture was also increased (unadjusted model: HR, 1.46; 95% CI, 1.13
      1.89; adjusted model: HR, 1.32; 95% CI, 1.02-1.71). In fully-adjusted models, the
      association of incident lower extremity fracture with increased mortality was
      substantially greater in older men (age >=50 years) for the entire cohort (HR,
      3.42; 95% CI, 2.75-4.25) and for those with complete SCI (HR, 3.13; 95% CI, 2.19
      4.45), compared to younger men (age <50 years) (entire cohort: HR, 1.42; 95% CI,
      0.94-2.14; complete SCI: HR, 1.71; 95% CI, 0.98-3.01). Every additional point in
      the Charlson comorbidity index was associated with a 10% increase in the hazard
      of death in models involving the entire cohort (HR, 1.11; 95% CI, 1.09-1.13) and
      also in models limited to men with complete SCI (HR, 1.10; 95% CI, 1.06-1.15).
      These data support the concept that both the fracture itself and underlying
      comorbidities are drivers of death in men with SCI.

PMID- 23873735
TI  - Propagation of biochirality: crossovers and nonclassical crystallization kinetics
      of aspartic acid in water.
AB  - All experimental procedures discussed could be treated as a screening tool for
      probing the existence of molecular association among the chiral molecules and the
      solvent system. The molecular association phases of a racemic conglomerate
      solution (CS) and a racemic compound solution (RCS), and the templating effect of
      aspartic acid solid surface were observed to minimize the chance of redissolving
      racemic conglomerate and racemic compound aspartic acid in water and reforming an
      RCS in crossovers experiments. Only 1 %wt% of l-aspartic acid was adequate enough
      to induce a transformation from a racemic compound aspartic acid to a racemic
      conglomerate aspartic acid. This would make the propagation of biochirality more
      feasible and sound. However, tetrapeptide, (l-aspartic acid)4 , failed to induce
      enantioseparation as templates purely by crystallization. Nonclassical
      crystallization theory was needed to take into account the existence of a CS.
      Fundamental parameters of the crystallization kinetics such as the induction
      time, interfacial energy, Gibbs energetic barrier, nucleation rate, and critical
      size of stable nuclei of: (i) racemic compound aspartic acid, (ii) racemic
      compound aspartic acid seeded with 1 %wt% l-aspartic acid, (iii) racemic
      conglomerate aspartic acid, and (iv) l-aspartic acid were evaluated and compared
      with different initial supersaturation ratios. Morphological studies of crystals
      grown from the crystallization kinetics were also carried out.

PMID- 23873734
TI  - Defective dendritic cell response to Toll-like receptor 7/8 agonists in
      perinatally HIV-infected children.
AB  - Understanding the defects in innate immunity associated with perinatal HIV
      infection is a prerequisite for effective antiretroviral treatment. We therefore
      compared the innate immune response [dendritic cell (DC) phenotype and function]
      in peripheral blood by flow cytometry at baseline and 12 months in HIV-infected
      children to determine the defect associated with perinatal HIV infection. As
      compared with controls, patients had decreased numbers of total DCs including
      plasmacytoid (p)DCs and myeloid (m)DCs and impaired function based on induction
      of maturation markers (CD83, CD80, CCR7) and cytokines tumor necrosis factor
      alpha and interferon-alpha (exclusive to pDC) upon stimulation with the TLR7/8
      agonist Resiquimod. These abnormalities were evident in all three CD4 immune
      categories and persisted over 12 months; pDC function worsened in HIV+ children
      without treatment and improved slightly in those on highly active antiretroviral
      therapy (HAART). In conclusion, a majority of perinatally HIV-infected older
      children without HAART remain clinically stable in the short term, but have
      demonstrable immunologic abnormalities indicative of defects in the innate immune
      system. Children initiated on HAART showed improvement in CD4 counts but did not
      show improvement in DC function over the short term.

PMID- 23873736
TI  - Backcasting the decline of a vulnerable Great Plains reproductive ecotype:
      identifying threats and conservation priorities.
AB  - Conservation efforts for threatened or endangered species are challenging because
      the multi-scale factors that relate to their decline or inhibit their recovery
      are often unknown. To further exacerbate matters, the perceptions associated with
      the mechanisms of species decline are often viewed myopically rather than across
      the entire species range. We used over 80 years of fish presence data collected
      from the Great Plains and associated ecoregions of the United States, to
      investigate the relative influence of changing environmental factors on the
      historic and current truncated distributions of the Arkansas River shiner
      Notropis girardi. Arkansas River shiner represent a threatened reproductive
      ecotype considered especially well adapted to the harsh environmental extremes of
      the Great Plains. Historic (n = 163 records) and current (n = 47 records) species
      distribution models were constructed using a vector-based approach in MaxEnt by
      splitting the available data at a time when Arkansas River shiner dramatically
      declined. Discharge and stream order were significant predictors in both models;
      however, the shape of the relationship between the predictors and species
      presence varied between time periods. Drift distance (river fragment length
      available for ichthyoplankton downstream drift before meeting a barrier) was a
      more important predictor in the current model and indicated river segments 375
      780 km had the highest probability of species presence. Performance for the
      historic and current models was high (area under the curve; AUC > 0.95); however,
      forecasting and backcasting to alternative time periods suggested less predictive
      power. Our results identify fragments that could be considered refuges for
      endemic plains fish species and we highlight significant environmental factors
      (e.g., discharge) that could be manipulated to aid recovery. 

PMID- 23873738
TI  - Photoinduced twisting of a photochromic diarylethene crystal.

PMID- 23873737
TI  - Thiuram disulfides as pseudo-irreversible inhibitors of lymphoid tyrosine
      phosphatase.
AB  - We screened a small library of thiuram disulfides for inhibition of lymphoid
      tyrosine phosphatase (LYP) activity. The parent thiuram disulfide, disulfiram,
      inhibited LYP activity in vitro and in Jurkat T cells, whereas
      diethyldithiocarbamate failed to inhibit LYP at the concentrations tested.
      Compound 13, an N-(2-thioxothiazolidin-4-one) analogue, was found to be the most
      potent LYP inhibitor in this series, with an IC50 value of 3 MUM. Compound 13
      inhibits LYP pseudo-irreversibly, as evidenced by the time-dependence of
      inhibition, with a K(i) value of 1.1 MUM and a k(inact) value of 0.004 s-1. The
      inhibition of LYP by compound 13 could not be reversed significantly by
      incubation with glutathione or by prolonged dialysis, but could be partially
      reversed by incubation with dithiothreitol. Compound 13 also inhibited LYP
      activity in Jurkat T cells.

PMID- 23873739
TI  - Hospital-acquired anemia: prevalence, outcomes, and healthcare implications.
AB  - BACKGROUND: Evidence suggests that patients with normal hemoglobin (Hgb) levels
      on hospital admission who subsequently develop hospital-acquired anemia (HAA) may
      be at risk for adverse outcomes. Our objectives were to (1) determine the
      prevalence of HAA and (2) examine whether HAA is associated with increased
      mortality, length of stay (LOS), and total hospital charges. METHODS: The
      population consisted of 417,301 adult hospitalizations from January 1, 2009 to
      August 31, 2011, in an academic medical center and 9 community hospitals.
      Patients with anemia on admission, and hospitals in the health system without
      available laboratory data were excluded; 188,447 hospitalizations were included
      in the analysis. Demographics, comorbidities, and outcomes were retrieved from
      administrative data; Hgb values were taken from the electronic medical record.
      Regression modeling was used to examine the association between demographics,
      comorbidity, hospitalization type, and HAA variables (mild: Hgb >11 and <12 g/dL
      for women, and >11 and <13 g/dL for men; moderate: Hgb 9.1 to <= 11.0 g/dL;
      severe: Hgb <= 9.0 g/dL) on mortality, LOS, and hospital charges. RESULTS: Among
      188,447 hospitalizations, 139,807 patients (74%) developed HAA: mild, 40,828
      (29%); moderate, 57,184 (41%); and severe, 41,795 (30%). Risk-adjusted odds
      ratios and 95% confidence intervals for in-hospital mortality with HAA were:
      mild, 1.0 (0.88-1.17; P = 0.8); moderate, 1.51 (1.33-1.71, P < 0.001); and
      severe, 3.28 (2.90-3.72, P < 0.001). Risk-adjusted relative mean LOS and hospital
      charges relative to no HAA were higher with HAA: LOS: mild, 1.08 (1.08-1.10, P <
      0.001); moderate, 1.28 (1.26-1.29, P < 0.001); severe, 1.88 (1.86-1.89, P <
      0.001). Hospital charges: mild, 1.06 (1.06-1.07, P < 0.001); moderate, 1.18 (1.17
      1.19, P < 0.001); severe, 1.80 (1.79-1.82, P < 0.001). CONCLUSIONS: HAA is common
      and associated with increased mortality and resource utilization. Factors related
      to its development necessitate further study.

PMID- 23873740
TI  - The influence of insecticides on the viability of entomopathogenic nematodes
      (Rhabditida: Steinernematidae and Heterorhabditidae) under laboratory conditions.
AB  - BACKGROUND: In order to increase our knowledge on the susceptibility of
      entomopathogenic nematode (EPN) species to agrochemicals, the compatibility of
      the infective juveniles (IJs) of the EPN (Steinernema and Heterorhabditis) with
      eight chemical and bio-insecticides was investigated under laboratory conditions.
      The effect of direct IJ exposure to insecticides for 6 and 24 h was tested in a
      Petri dish at 15, 20 and 25  degrees C. RESULTS: The study showed that S.
      carpocapsae and S. kraussei are sensitive to all tested insecticides. Steinernema
      feltiae is compatible with azadirachtin, toxin of Bacillus thuringiensis var.
      kurstaki and imidacloprid, while H. bacteriophora is sensitive only to abamectin
      and lufenuron. The percentage of IJs that survived was statistically the highest
      after 6 h at 15  degrees C (82%) and 20  degrees C (80%). At 25  degrees C (76%)
      it was statistically the lowest. After 24 h there were no statistically
      significant differences observed between 15  degrees C (55%) and 20  degrees C
      (55%), while at 25  degrees C, the statistically largest percentage of IJs (59%)
      survived. CONCLUSION: Based on our research, we conclude that compatibility is
      not only a species-specific, but also a strain-specific characteristic.
      Steinernema feltiae and H. bacteriophora are compatible with azadirachtin and
      pirimicarb and might offer a cost-effective alternative to pest control against
      different vegetable pests. (c) 2013 Society of Chemical Industry.

PMID- 23873742
TI  - Two-step pH-modulated rapid assembly of trace-element-doped calcium-phosphate
      nanocrystals into giant porous beads in gelatin hydrosol for biomedical
      applications.
AB  - Biomolecule-ion interactions that occur during changes in pH value are a crucial
      but poorly investigated area that underlies the aggregation of inorganic
      nanocrystals. Meanwhile, the disorderly growth of calcium phosphate (CaP)
      nanocrystals is an obstacle that limits its practical applications. Herein, we
      have demonstrated for the first time that a simple two-step pH-adjustment process
      for a gelatin hydrosol reaction medium can modulate the ordered self-assembly of
      trace-element-doped CaP nanocrystals into porous beads. Two methods are used to
      adjust the initial pH value of gelatin hydrosol: One is to firstly adjust the pH
      value to 3.0 and then to 4.0 with acid/base solutions, whilst the other is to
      directly adjust the pH value to 4.0 with acid. Spherical CaP porous beads are
      rapidly produced through the two-step pH-adjustment process, whereas the one-step
      pathway results in disorderly CaP aggregates. We believe that the introduction of
      additives for pH adjustment is the dominant factor in disturbing the
      electrokinetic parameters and for driving the self-assembly of nanocrystals,
      whereas the nucleation of CaP nanocrystals prior to assembly is caused by the
      relaxation/condensation of the polypeptide network, owing to the increase in pH
      value on the introduction of the basic calcium salt. This method is facile and
      rapid and these highly bioactive porous beads are particularly promising for use
      in hard-tissue repair, tissue engineering, and drug delivery. 

PMID- 23873741
TI  - Relationship of weight, height, and body mass index with fracture risk at
      different sites in postmenopausal women: the Global Longitudinal study of
      Osteoporosis in Women (GLOW).
AB  - Low body mass index (BMI) is a well-established risk factor for fracture in
      postmenopausal women. Height and obesity have also been associated with increased
      fracture risk at some sites. We investigated the relationships of weight, BMI,
      and height with incident clinical fracture in a practice-based cohort of
      postmenopausal women participating in the Global Longitudinal study of
      Osteoporosis in Women (GLOW). Data were collected at baseline and at 1, 2, and 3
      years. For hip, spine, wrist, pelvis, rib, upper arm/shoulder, clavicle, ankle,
      lower leg, and upper leg fractures, we modeled the time to incident self-reported
      fracture over a 3-year period using the Cox proportional hazards model and fitted
      the best linear or nonlinear models containing height, weight, and BMI. Of 52,939
      women, 3628 (6.9%) reported an incident clinical fracture during the 3-year
      follow-up period. Linear BMI showed a significant inverse association with hip,
      clinical spine, and wrist fractures: adjusted hazard ratios (HRs) (95% confidence
      intervals [CIs]) per increase of 5 kg/m(2) were 0.80 (0.71-0.90), 0.83 (0.76
      0.92), and 0.88 (0.83-0.94), respectively (all p < 0.001). For ankle fractures,
      linear weight showed a significant positive association: adjusted HR per 5-kg
      increase 1.05 (1.02-1.07) (p < 0.001). For upper arm/shoulder and clavicle
      fractures, only linear height was significantly associated: adjusted HRs per 10
      cm increase were 0.85 (0.75-0.97) (p = 0.02) and 0.73 (0.57-0.92) (p = 0.009),
      respectively. For pelvic and rib fractures, the best models were for nonlinear
      BMI or weight (p = 0.05 and 0.03, respectively), with inverse associations at low
      BMI/body weight and positive associations at high values. These data demonstrate
      that the relationships between fracture and weight, BMI, and height are site
      specific. The different associations may be mediated, at least in part, by
      effects on bone mineral density, bone structure and geometry, and patterns of
      falling.

PMID- 23873743
TI  - Size-Dependent Enhancement of Electrocatalytic Oxygen-Reduction and Hydrogen
      Evolution Performance of MoS2 Particles.
AB  - MoS2 particles with different size distributions were prepared by simple
      ultrasonication of bulk MoS2 followed by gradient centrifugation. Relative to the
      inert microscale MoS2, nanoscale MoS2 showed significantly improved catalytic
      activity toward the oxygen-reduction reaction (ORR) and hydrogen-evolution
      reaction (HER). The decrease in particle size was accompanied by an increase in
      catalytic activity. Particles with a size of around 2 nm exhibited the best dual
      ORR and HER performance with a four-electron ORR process and an HER onset
      potential of -0.16 V versus the standard hydrogen electrode (SHE). This is the
      first investigation on the size-dependent effect of the ORR activity of MoS2, and
      a four-electron transfer route was found. The exposed abundant Mo edges of the
      MoS2 nanoparticles were proven to be responsible for the high ORR catalytic
      activity, whereas the origin of the improved HER activity of the nanoparticles
      was attributed to the plentiful exposed S edges. This newly discovered process
      provides a simple protocol to produce inexpensive highly active MoS2 catalysts
      that could easily be scaled up. Hence, it opens up possibilities for wide
      applications of MoS2 nanoparticles in the fields of energy conversion and
      storage.

PMID- 23873744
TI  - Asymmetric electrophilic fluorocyclization with carbon nucleophiles.

PMID- 23873745
TI  - An oral vaccine against candidiasis generated by a yeast molecular display
      system.
AB  - Enolase 1 (Eno1p) of Candida albicans is an immunodominant antigen. However,
      conventional technologies for preparing an injectable vaccine require
      purification of the antigenic protein and preparation of an adjuvant. To develop
      a novel type of oral vaccine against candidiasis, we generated Saccharomyces
      cerevisiae cells that display the Eno1p antigen on their surfaces. Oral delivery
      of the engineered S. cerevisiae cells prolonged survival rate of mice that were
      subsequently challenged with C. albicans. Given that a vaccine produced using
      molecular display technology avoids the need for protein purification, this oral
      vaccine offers a promising alternative to the use of conventional and injectable
      vaccines for preventing a range of infectious diseases. 

PMID- 23873746
TI  - Effects of unilateral stereotactic posterior striatotomy on harmaline-induced
      tremor in rats.
AB  - Although long known and the most prevalent movement disorder, pathophysiology of
      essential tremor (ET) remains controversial. The most accepted hypothesis is that
      it is caused by a dysfunction of the olivocerebellar system. Vilela Filho et al.
      [2001; Stereotact Funct Neurosurg 77:149-150], however, reported a patient with
      unilateral hand ET that was completely relieved after a stroke restricted to the
      contralateral posterior putamen and suggested that ET could be the clinical
      manifestation of posterior putamen hyperactivity. The present study was designed
      to evaluate this hypothesis in the most often used model of ET, harmaline-induced
      tremor in rats. Fifty-four male Wistar rats were randomly distributed into three
      groups: experimental (EG), surgical control (SCG), and pharmacological control
      (PCG) groups. EG animals underwent stereotactic unilateral posterior striatotomy.
      SCG rats underwent sham lesion at the same target. PCG served exclusively as
      controls for harmaline effects. All animals received, postoperatively,
      intraperitoneal harmaline, and the induced tremor was video-recorded for later
      evaluation by a blind observer. Thirteen animals were excluded from the study.
      Limb tremor was reduced ipsilaterally to the operation in 20 of 21 rats of EG and
      in two of nine of SCG, being asymmetric in one of 10 of PCG rats. Comparisons
      between EG * SCG and EG * PCG were statistically significant, but not between SCG
      * PCG. Limb tremor reduction was greater in anterior than in posterior paws.
      Lateral lesions yielded better results than medial lesions. These results suggest
      that the posterior striatum is involved with harmaline-induced tremor in rats and
      support the hypothesis presented.

PMID- 23873747
TI  - Environmental controls of temporal and spatial variability in CO2 and CH4 fluxes
      in a neotropical peatland.
AB  - Tropical peatlands play an important role in the global storage and cycling of
      carbon (C) but information on carbon dioxide (CO2) and methane (CH4) fluxes from
      these systems is sparse, particularly in the Neotropics. We quantified short and
      long-term temporal and small scale spatial variation in CO2 and CH4 fluxes from
      three contrasting vegetation communities in a domed ombrotrophic peatland in
      Panama. There was significant variation in CO2 fluxes among vegetation
      communities in the order Campnosperma panamensis > Raphia taedigera > Cyperus.
      There was no consistent variation among sites and no discernible seasonal pattern
      of CH4 flux despite the considerable range of values recorded (e.g. -1.0 to 12.6
      mg m(-2) h(-1) in 2007). CO2 fluxes varied seasonally in 2007, being greatest in
      drier periods (300-400 mg m(-2) h(-1)) and lowest during the wet period (60-132
      mg m(-2) h(-1)) while very high emissions were found during the 2009 wet period,
      suggesting that peak CO2 fluxes may occur following both low and high rainfall.
      In contrast, only weak relationships between CH4 flux and rainfall (positive at
      the C. panamensis site) and solar radiation (negative at the C. panamensis and
      Cyperus sites) was found. CO2 fluxes showed a diurnal pattern across sites and at
      the Cyperus sp. site CO2 and CH4 fluxes were positively correlated. The amount of
      dissolved carbon and nutrients were strong predictors of small scale within-site
      variability in gas release but the effect was site-specific. We conclude that (i)
      temporal variability in CO2 was greater than variation among vegetation
      communities; (ii) rainfall may be a good predictor of CO2 emissions from tropical
      peatlands but temporal variation in CH4 does not follow seasonal rainfall
      patterns; and (iii) diurnal variation in CO2 fluxes across different vegetation
      communities can be described by a Fourier model.

PMID- 23873748
TI  - Fast evolving nanotechnology and progress in the National Center for Nanoscience
      and Technology of China.

PMID- 23873749
TI  - BOOST: evidence needing a lift.

PMID- 23873750
TI  - A short note on economic development and socioeconomic inequality in female body
      weight.
AB  - The origin of the obesity epidemic in developing countries is still poorly
      understood. It has been prominently argued that economic development provides a
      natural interpretation of the growth in obesity. This paper tests the main
      aggregated predictions of the theoretical framework to analyze obesity. Average
      body weight and health inequality should be associated with economic development.
      Both hypotheses are confirmed: we find higher average female body weight in
      economically more advanced countries. In relatively nondeveloped countries,
      obesity is a phenomenon of the socioeconomic elite. With economic development,
      obesity shifts toward individuals with lower socioeconomic status.

PMID- 23873751
TI  - Liver transplantation and autoimmune liver diseases.
AB  - Liver transplantation (LT) is an effective treatment for patients with end-stage
      autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing
      cholangitis, and autoimmune hepatitis. Indications for LT for these diseases do
      not differ substantially from those used for other acute or chronic liver
      diseases. Despite the good outcomes reported, the recurrence of autoimmune liver
      disease is relatively common in the allograft. In addition, it has become
      apparent that autoimmunity and autoimmune liver disease can arise de novo after
      transplantation for nonautoimmune liver disorders. An awareness of the existence
      of recurrent autoimmune liver diseases and de novo autoimmune hepatitis after LT
      has important clinical implications because their management differs from the
      standard antirejection treatment and is similar to the management of classic
      autoimmune liver diseases in the native liver.

PMID- 23873752
TI  - Accuracy and precision of photoacoustic spectroscopy not guaranteed.

PMID- 23873753
TI  - The protective effect of immunoglobulin in murine tuberculosis is dependent on
      IgG glycosylation.
AB  - Antibodies have demonstrated having a protective effect in animal models of
      tuberculosis (TB). These experiments have considered the specificity of antigen
      recognition and the different isotypes and subclasses as significant contributors
      of this effect. However, the carbohydrate chain heterogeneity on the Fc region of
      IgG (Fc-IgG) can play an important role in modulating the immune response.
      Patients with TB usually have high titers of specific IgG; however, the
      carbohydrate associated with Fc-IgG usually lacks galactose. To assess the effect
      of this abnormal IgG in murine pulmonary TB, we evaluated the specificity of
      recognition to Mycobacterium tuberculosis antigens in vitro and protective
      effects in vivo comparing human intravenous immunoglobulin (IVIg) and IVIg
      treated with an endoglycosidase to remove the glycan residues (EndoS-treated
      IVIg). Our results showed similar antigen recognition. The study of distribution
      and kinetics of IVIg in serum and bronchial lavage after intraperitoneal (i.p.)
      administration in mice showed that IVIg circulates for 21 days. Finally, the
      protective effect of intact and EndoS-treated IVIg administered by i.p was
      studied in a murine model of progressive TB. IVIg treatment caused reduction in
      pulmonary bacilli loads, larger granulomas, and less pneumonia, while animals
      treated with EndoS-treated IVIg were not protected compared with control animals.
      Thus, IVIg has a protective activity in experimental pulmonary TB, and this
      effect requires intact Fc oligosaccharides.

PMID- 23873754
TI  - Inflammatory acidic pH enhances hydrogen sulfide-induced transient receptor
      potential ankyrin 1 activation in RIN-14B cells.
AB  - Hydrogen sulfide (H2 S), a toxic volcanic gas, functions as a gaseous
      physiological and pathophysiological molecule. Recently we have shown that H2 S
      elicits acute pain through the activation of transient receptor potential ankyrin
      1 (TRPA1), which is expressed mainly in primary nociceptive neurons. We also
      demonstrated enhancement of H2 S-induced TRPA1 activation and pain under
      inflammatory acidic conditions, but the underlying mechanism has not been
      elucidated. Here, we attempted to clarify this mechanism by using endogenously
      TRPA1-expressing RIN-14B, a rat pancreatic islet cell line. For this purpose, the
      intracellular Ca(2+) concentration ([Ca(2+) ]i )], reactive oxygen species (ROS),
      and intracellular pH (pHi ) were measured with fluorescent imaging techniques.
      The intracellular H2 S concentration was assayed by the methylene blue method. To
      clarify the cellular function of H2 S, 5-hydroxytryptamine (5-HT) secretion was
      analyzed. In RIN-14B, the increase of [Ca(2+) ]i and the release of 5-HT induced
      by NaHS, an H2 S donor, were enhanced under inflammatory acidic conditions.
      Transition of H2 S into cells was enhanced at pH 6.8. H2 S failed to increase the
      intracellular ROS level and only slightly decreased pHi . These results suggest
      that H2 S directly activates TRPA1 and that its increment of diffusion into cells
      may be involved in the potentiation of TRPA1 activation under external acidic
      conditions. Thus, our study supports the pathophysiological functions of H2 S in
      inflammatory pain.

PMID- 23873755
TI  - Crystal structures of [Fe]-hydrogenase in complex with inhibitory isocyanides:
      implications for the H2-activation site.

PMID- 23873756
TI  - Electronic health record-based triggers to detect potential delays in cancer
      diagnosis.
AB  - BACKGROUND: Delayed diagnosis of cancer can lead to patient harm, and strategies
      are needed to proactively and efficiently detect such delays in care. We aimed to
      develop and evaluate 'trigger' algorithms to electronically flag medical records
      of patients with potential delays in prostate and colorectal cancer (CRC)
      diagnosis. METHODS: We mined retrospective data from two large integrated health
      systems with comprehensive electronic health records (EHR) to iteratively develop
      triggers. Data mining algorithms identified all patient records with specific
      demographics and a lack of appropriate and timely follow-up actions on four
      diagnostic clues that were newly documented in the EHR: abnormal prostate
      specific antigen (PSA), positive faecal occult blood test (FOBT), iron-deficiency
      anaemia (IDA), and haematochezia. Triggers subsequently excluded patients not
      needing follow-up (eg, terminal illness) or who had already received appropriate
      and timely care. Each of the four final triggers was applied to a test cohort,
      and chart reviews of randomly selected records identified by the triggers were
      used to calculate positive predictive values (PPV). RESULTS: The PSA trigger was
      applied to records of 292 587 patients seen between 1 January 2009 and 31
      December 2009, and the CRC triggers were applied to 291 773 patients seen between
      1 March 2009 and 28 February 2010. Overall, 1564 trigger positive patients were
      identified (426 PSA, 355 FOBT, 610 IDA and 173 haematochezia). Record reviews
      revealed PPVs of 70.2%, 66.7%, 67.5%, and 58.3% for the PSA, FOBT, IDA and
      haematochezia triggers, respectively. Use of all four triggers at the study sites
      could detect an estimated 1048 instances of delayed or missed follow-up of
      abnormal findings annually and 47 high-grade cancers. CONCLUSIONS: EHR-based
      triggers can be used successfully to flag patient records lacking follow-up of
      abnormal clinical findings suspicious for cancer.

PMID- 23873757
TI  - The role of technology in clinician-to-clinician communication.
AB  - Incomplete, fragmented and poorly organised communications contribute to more
      than half the errors that lead to adverse and sentinel events. Meanwhile,
      communication software and devices with expanding capabilities are rapidly
      proliferating and being introduced into the healthcare setting. Clinicians face a
      large communication burden, which has been exacerbated by the additional
      challenge of selecting a mode of communication. In addition to specific
      communication devices, some hospitals have implemented advanced technological
      systems to assist with communication. However, few studies have provided
      empirical evidence of the specific advantages and disadvantages of the different
      devices used for communication. Given the increasing quantities of information
      transmitted to and by clinicians, evaluations of how communication methods and
      devices can improve the quality, safety and outcomes of healthcare are needed. 

PMID- 23873758
TI  - Set7/9 impacts COL2A1 expression through binding and repression of SirT1 histone
      deacetylation.
AB  - Type II collagen is a key cartilaginous extracellular protein required for normal
      endochondral development and cartilage homeostasis. COL2A1 gene expression is
      positively regulated by the NAD-dependent protein deacetylase Sirtuin 1 (SirT1),
      through its ability to bind chromatin regions of the COL2A1 promoter and
      enhancer. Although SirT1/Sox9 binding on the enhancer site of COL2A1 was
      previously demonstrated, little is known about its functional role on the gene
      promoter site. Here, we examined the mechanism by which promoter-associated SirT1
      governs COL2A1 expression. Human chondrocytes were encapsulated in three
      dimensional (3D) alginate beads where they exhibited upregulated COL2A1 mRNA
      expression and increased levels of SirT1 occupancy on the promoter and enhancer
      regions, when compared to monolayer controls. Chromatin immunoprecipitation
      (ChIP) analyses of 3D cultures showed augmented levels of the DNA-binding
      transcription factor SP1, and the histone methyltransferase Set7/9, on the COL2A1
      promoter site. ChIP reChIP assays revealed that SirT1 and Set7/9 form a protein
      complex on the COL2A1 promoter region of 3D-cultured chondrocytes, which also
      demonstrated elevated trimethylated lysine 4 on histone 3 (3MeH3K4), a hallmark
      of Set7/9 methyltransferase activity. Advanced passaging of chondrocytes yielded
      a decrease in 3MeH3K4 and Set7/9 levels on the COL2A1 promoter and reduced COL2A1
      expression, suggesting that the SirT1/Set7/9 complex is preferentially formed on
      the COL2A1 promoter and required for gene activation. Interestingly, despite
      SirT1 occupancy, its deacetylation targets (ie, H3K9/14 and H4K16) were found
      acetylated on the COL2A1 promoter of 3D-cultured chondrocytes. A possible
      explanation for this phenotype is the enrichment of the histone
      acetyltransferases P300 and GCN5 on the COL2A1 promoter of3 D-cultured
      chondrocytes. Our study indicates that Set7/9 prevents the histone deacetylase
      activity of SirT1, potentiating euchromatin formation on the promoter site of
      COL2A1 and resulting in morphology-dependent COL2A1 gene transactivation.

PMID- 23873759
TI  - Re-examination of the C(6)Li(6) structure: to be, or not to be symmetric.
AB  - The potential energy surface of C6 Li6 was re-examined and a new non-symmetric
      global minimum was found. The new structure can be described as three C2 (2-)
      fragments strongly aggregated through lithium bridges. At high temperatures,
      fluxionality is perceived instead of dissociation. At 600 and 900 K, the BOMD
      simulations show that the lithium mobility is high, indicating that the cluster
      behaves in a liquid-like manner (BOMD=Born-Oppenheimer molecular dynamics).

PMID- 23873760
TI  - In situ atomic-scale imaging of phase boundary migration in FePO(4)
      microparticles during electrochemical lithiation.
AB  - The electrochemical lithiation of FePO4 particles is investigated by in situ high
      resolution transmission electron microscopy (HRTEM), and the anisotropic
      lithiation mechanism is directly observed. For the first time and in contrast to
      the previous post mortem HRTEM observations, a sharp (010) phase boundary between
      LiFePO4 and FePO4 is observed, which migrates along the [010] direction during
      lithiation. 

PMID- 23873761
TI  - BOOST and readmissions: thinking beyond the walls of the hospital.

PMID- 23873762
TI  - Patient safety in hospitals - a Bayesian analysis of unobservable hospital and
      specialty level risk factors.
AB  - This paper demonstrates how Bayesian hierarchical modelling can be used to
      evaluate the performance of hospitals. We estimate a three-level random intercept
      probit model to attribute unexplained variation in hospital-acquired
      complications to hospital effects, hospital-specialty effects and remaining
      random variations, controlling for observable patient complexities. The combined
      information provided by the posterior means and densities for latent hospital and
      specialty effects can be used to assess the need and scope for improvements in
      patient safety at different organizational levels. Posterior densities are not
      conventionally presented in performance assessment but provides valuable
      additional information to policy makers on what poorly performing hospitals and
      specialties may be prioritized for policy action. We use surgical patient
      administrative data for 2005/2006 for 16 specialties in 35 public hospitals in
      Victoria, Australia. We use posterior means for latent hospital and specialty
      effects to compare hospital performance in patient safety. Posterior densities
      and variances are also compared for different specialties to identify clinical
      areas with greatest scope for improvement. We also show that the same hospital
      may rank markedly differently for different specialties.

PMID- 23873763
TI  - Chondrogenic potential of human mesenchymal stem cells and expression of Slug
      transcription factor.
AB  - The scientific literature rarely reports experimental failures or inconsistent
      outcomes in the induction of cell differentiation; however, researchers commonly
      experience poor or unsuccessful responses to differentiating agents when
      culturing stem cells. One way of investigating the underlying reasons for such
      responses is to look at the basal expression levels of specific genes in
      multipotent stem cells before the induction of differentiation. In addition to
      shedding light on the complex properties of stem cells and the molecular
      modulation of differentiation pathways, this strategy can also lead to the
      development of important time- and money-saving tools that aid the efficient
      selection of cellular specimens--in this case, stem cells that are more prone to
      differentiate towards specific lineages and are therefore more suitable for cell
      based therapeutic protocols in regenerative medicine. To address this latter
      aspect, this study focused on understanding the reasons why some human
      mesenchymal stem cell (hMSC) samples are less efficient at differentiating
      towards chondrogenesis. This study shows that analysis of the basal expression
      levels of Slug, a negative regulator of chondrogenesis in hMSC, provides a rapid
      and simple tool for distinguishing stem cell samples with the potential to form a
      cartilage-like matrix, and that are therefore suitable for cartilage tissue
      engineering. It is shown that high basal levels of Slug prevent the chondrogenic
      differentiation of hMSCs, even in the presence of transforming growth factor-beta
      and elevated levels of Sox9.

PMID- 23873764
TI  - Alpha-fetoprotein and modified response evaluation criteria in solid tumors
      progression after locoregional therapy as predictors of hepatocellular cancer
      recurrence and death after transplantation.
AB  - Locoregional therapy (LRT) is being increasingly used for the management of
      hepatocellular cancer (HCC) in patients listed for liver transplantation (LT).
      Although several selection criteria have been developed, stratifications of
      survival according to the pathology of explanted livers and pre-LT LRT are
      lacking. Radiological progression according to the modified Response Evaluation
      Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was
      reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients
      outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999
      and March 2010. A prospectively collected database originating from 6
      collaborating European centers was used for the study. Sixty-one patients (14.5%)
      developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15
      ng/mL/month and mRECIST progression were unique independent risk factors for HCC
      recurrence and patient death. When the radiological Milan criteria (MC) status
      was combined with radiological and biological progression, MC-IN and MC-OUT
      patients without risk factors had similarly excellent 5-year tumor-free and
      patient survival rates. MC-IN patients with at least 1 risk factor had worse
      outcomes, and MC-OUT patients with at least 1 risk factor had the poorest
      survival (P < 0.001). In conclusion, both radiological and biological
      modifications permit documentation of the response to LRT in patients waiting for
      LT. According to these 2 parameters, tumor progression significantly increases
      the risk of recurrence and patient death not only for MC-OUT patients but also
      for MC-IN patients. The monitoring of both parameters in combination with the
      initial radiological MC status is an essential element for further refining the
      selection criteria for potential liver recipients with HCC.

PMID- 23873766
TI  - Introduction of fluorine and fluorine-containing functional groups.
AB  - Over the past decade, the most significant, conceptual advances in the field of
      fluorination were enabled most prominently by organo- and transition-metal
      catalysis. The most challenging transformation remains the formation of the
      parent C-F bond, primarily as a consequence of the high hydration energy of
      fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine.
      Most fluorination reactions still lack generality, predictability, and cost
      efficiency. Despite all current limitations, modern fluorination methods have
      made fluorinated molecules more readily available than ever before and have begun
      to have an impact on research areas that do not require large amounts of
      material, such as drug discovery and positron emission tomography. This Review
      gives a brief summary of conventional fluorination reactions, including those
      reactions that introduce fluorinated functional groups, and focuses on modern
      developments in the field.

PMID- 23873765
TI  - Genus-optimized strategy for the identification of chlamydial type III secretion
      substrates.
AB  - Among chlamydial virulence factors are the type III secretion (T3S) system and
      its effectors. T3S effectors target host proteins to benefit the infecting
      chlamydiae. The assortment of effectors, each with a unique function, varies
      between species. This variation likely contributes to differences in host
      specificity and disease severity. A dozen effectors of Chlamydia trachomatis have
      been identified; however, estimates suggest that more exist. A T3S prediction
      algorithm, SVM-based Identification and Evaluation of Virulence Effectors
      (SIEVE), along with a Yersinia surrogate secretion system helped to identify a
      new T3S substrate, CT082, which rather than functioning as an effector associates
      with the chlamydial envelope after secretion. SIEVE was modified to
      improve/expand effector predictions to include all sequenced genomes. Additional
      adjustments were made to the existing surrogate system whereby the N terminus of
      putative effectors was fused to a known effector lacking its own N terminus and
      was tested for secretion. Expansion of effector predictions by cSIEVE and
      modification of the surrogate system have also assisted in identifying a new T3S
      substrate from C. psittaci. The expanded predictions along with modifications to
      improve the surrogate secretion system have enhanced our ability to identify
      novel species-specific effectors, which upon characterization should provide
      insight into the unique pathogenic properties of each species. 

PMID- 23873767
TI  - Obesity and thyroid cancer: is leptin the (only) link?

PMID- 23873768
TI  - Is timing everything? New insights into why the effect of estrogen therapy on
      memory might be age dependent.

PMID- 23873769
TI  - How much kissing is required for fertility?

PMID- 23873770
TI  - Cardiac insulin resistance: it's sweeter than you think.

PMID- 23873771
TI  - iBAT on bone.

PMID- 23873772
TI  - Decreased survival in normal karyotype AML with single-nucleotide polymorphisms
      in genes encoding the AraC metabolizing enzymes cytidine deaminase and 5'
      nucleotidase.
AB  - De novo acute myeloid leukemia with normal karyotype (NK-AML) comprises a large
      group of patients with no common cytogenetic alterations and with a large
      variation in treatment response. Single-nucleotide polymorphisms (SNPs) in genes
      related to the metabolism of the nucleoside analogue AraC, the backbone in AML
      treatment, might affect drug sensitivity and treatment outcome. Therefore, SNPs
      may serve as prognostic biomarkers aiding clinicians in individualized treatment
      decisions, with the aim of improving patient outcomes. We analyzed polymorphisms
      in genes encoding cytidine deaminase (CDA 79A>C rs2072671 and -451C>T rs532545),
      5'-nucleotidase (cN-II 7A>G rs10883841), and deoxycytidine kinase (DCK 3'UTR
      948T>C rs4643786) in 205 de novo NK-AML patients. In FLT3-internal tandem
      duplication (ITD)-positive patients, the CDA 79C/C and -451T/T genotypes were
      associated with shorter overall survival compared to other genotypes (5 vs. 24
      months, P < 0.001 and 5 vs. 23 months, P = 0.015, respectively), and this was
      most pronounced in FLT3-ITD-positive/NPM1-positive patients. We observed altered
      in vitro sensitivity to topoisomerase inhibitory drugs, but not to nucleoside
      analogues, and a decrease in global DNA methylation in cells carrying both CDA
      variant alleles. A shorter survival was also observed for the cN-II variant
      allele, but only in FLT3-ITD-negative patients (25 vs. 31 months, P = 0.075). Our
      results indicate that polymorphisms in genes related to nucleoside analog drug
      metabolism may serve as prognostic markers in de novo NK-AML.

PMID- 23873773
TI  - Aggregation-induced emission and efficient solid-state fluorescence from
      tetraphenylethene-based N,C-chelate four-coordinate organoborons.
AB  - In it together: Thermally stable N,C-chelate four-coordinate organoborons were
      attained by grafting intramolecular B? ? ?N coordination into tetraphenylethene
      pyridine and -quinoline adducts. They exhibit aggregation-induced emission
      characteristics (see figure), and high fluorescence quantum yields approaching
      unity in solid films.

PMID- 23873774
TI  - Response to "Critical growth temperature of aqueous CdTe quantum dots is non
      negligible for their application as nanothermometers".

PMID- 23873775
TI  - Topography from topology: photoinduced surface features generated in liquid
      crystal polymer networks.
AB  - Films subsumed with topological defects are transformed into complex,
      topographical surface features with light irradiation of azobenzene
      functionalized liquid crystal polymer networks (azo-LCNs). Using a specially
      designed optical setup and photoalignment materials, azo-LCN films containing
      either singular or multiple defects with strengths ranging from |1/2| to as much
      as |10| are examined. The local order of an azo-LCN material for a given defect
      strength dictates a complex, mechanical response observed as topographical
      surface features. 

PMID- 23873776
TI  - Dietary acid load is associated with lower bone mineral density in men with low
      intake of dietary calcium.
AB  - High dietary acid load (DAL) may be detrimental to bone mineral density (BMD).
      The objectives of the study were to: (1) evaluate the cross-sectional relation
      between DAL and BMD; and (2) determine whether calcium intake modifies this
      association. Men (n = 1218) and women (n = 907) aged >=60 years were included
      from the National Health and Nutrition Examination Survey 2005-2008. Nutrient
      intake from 2, 24-hour recalls was used to calculate net endogenous acid
      production (NEAP) and potential renal acid load (PRAL) (mEq/d). PRAL was
      calculated from dietary calcium (PRALdiet ) and diet + supplemental calcium
      (PRALtotal ). Tests for linear trend in adjusted mean BMD of the hip and lumbar
      spine were performed across energy-adjusted NEAP and PRAL quartiles. Modification
      by calcium intake (dietary or total) above or below 800 mg/d was assessed by
      interaction terms. Overall, mean age was 69 +/- 0.3 years. Among women, there was
      no association between NEAP and BMD. PRALdiet was positively associated with
      proximal femur BMD (p trend = 0.04). No associations were observed with PRALtotal
      at any BMD site (p range, 0.38-0.82). Among men, no significant associations were
      observed between BMD and NEAP or PRAL. However, an interaction between PRALdiet
      and calcium intake was observed with proximal femur BMD (p = 0.08). An inverse
      association between PRALdiet and proximal femur BMD was detected among men with
      <800 mg/d dietary calcium (p = 0.02); no associations were found among men with
      >=800 mg/d (p = 0.98). A significant interaction with PRALtotal was not observed.
      In conclusion, when supplemental calcium is considered, there is no association
      between DAL and BMD among adults. Men with low dietary calcium showed an inverse
      relation with PRAL at the proximal femur; in women no interaction was observed.
      This study highlights the importance of calcium intake in counteracting the
      adverse effect of DAL on bone health. Further research should determine the
      relation between DAL and change in BMD with very low calcium intake.

PMID- 23873778
TI  - Pretransplant donor-specific anti-HLA antibodies as predictors of early allograft
      rejection in ABO-compatible liver transplantation.
AB  - The significance of preexisting donor-specific HLA antibodies (HLA-DSAs) for
      liver allograft function is unclear. Our previous studies have shown that humoral
      alloreactivity frequently accompanies acute cellular rejection (ACR). In the
      present study, we set out to determine whether pretransplant HLA-DSAs correlate
      with clinically significant ACR in the first 90 days after transplantation and,
      if so, to determine their predictive values. Class I HLA-DSAs and class II HLA
      DSAs were determined by single-antigen bead flow cytometry for 113 consecutive
      adult transplants. A statistical analysis was performed for data from 109
      consecutive patients with graft survival greater than or equal to 90 days. All
      patients who developed biochemical graft dysfunction underwent liver biopsy for
      hematoxylin-eosin and complement component 4d staining. Cox proportional hazards
      models and associated hazard ratios revealed a significant association of
      pretransplant HLA-DSAs with clinically significant ACR: this association started
      with a mean fluorescence intensity (MFI) as low as 300 for both class I (hazard
      ratio = 2.7, P  < 0.01) and class II (hazard ratio = 6.0, P  < 0.01).
      Pretransplant HLA-DSAs were associated with an increased risk of ACR: P  < 0.01
      for class I (42% versus 18%), P  < 0.001 for class II (37% versus 7%), and P  <
      0.001 for either class I or II (36% versus 3%). Class I or II HLA-DSAs with an
      MFI >= 1000 had the best positive predictive value for clinically significant ACR
      at 46%, whereas class I or II HLA-DSAs with an MFI >= 300 had the best negative
      predictive value at 97.1%. Although our study was based on consecutive patients,
      it was limited by the relatively low number of single-center subjects. In
      conclusion, the present study indicates that pretransplant HLA-DSAs, even at low
      levels of allosensitization, correlate with the risk of clinically significant
      ACR. Our findings suggest that anti-human leukocyte antigen antibodies could
      serve as donor-specific markers of immunoreactivity to the liver graft.

PMID- 23873779
TI  - Unraveling the interaction between the LPS O-antigen of Burkholderia anthina and
      the 5D8 monoclonal antibody by using a multidisciplinary chemical approach, with
      synthesis, NMR, and molecular modeling methods.
AB  - The interaction between the O-chain from the lipopolysaccharide from Burkholderia
      anthina and a lipopolysaccharide-specific monoclonal antibody (5D8) has been
      studied at high resolution by NMR spectroscopy. In particular, the 5D8-bound
      epitope of the saccharide entity has been unraveled by a combination of
      saturation transfer difference (STD) and transferred NOESY (tr-NOESY) experiments
      performed on the 5D8/polysaccharide complex. To dissect the fine details of the
      molecular recognition events, further experiments with simpler carbohydrate
      ligands were carried out. Thus, experiments were also performed with ad hoc
      synthesized trisaccharide and hexasaccharide O-antigen repeating units. By using
      this multidisciplinary approach (chemical synthesis, NMR spectroscopy and
      molecular dynamics simulation), determination of the binding epitope and the
      contribution to the binding of the sugar units composing the O-chain have been
      determined. 

PMID- 23873781
TI  - Heptacene: increased persistence of a 4n+2 pi-electron polycyclic aromatic
      hydrocarbon by oxidation to the 4n pi-electron dication.

PMID- 23873780
TI  - Enhanced tumor accumulation of sub-2 nm gold nanoclusters for cancer radiation
      therapy.
AB  - A new type of metabolizable and efficient radiosensitizers for cancer
      radiotherapy is presented by combining ultrasmall Au nanoclusters (NCs, <2 nm)
      with biocompatible coating ligands (glutathione, GSH). The new nanoconstruct (GSH
      coated Au25 NCs) inherits attractive features of both the Au core (strong
      radiosensitizing effect) and GSH shell (good biocompatibility). It can
      preferentially accumulate in tumor via the improved EPR effect, which leads to
      strong enhancement for cancer radiotherapy. After the treatment, the small-sized
      GSH-Au25 NCs can be efficiently cleared by the kidney, minimizing any potential
      side effects due to the accumulation of Au25 NCs in the body.

PMID- 23873782
TI  - Cultivation of Aquincola tertiaricarbonis L108 on the fuel oxygenate intermediate
      tert-butyl alcohol induces aerobic anoxygenic photosynthesis at extremely low
      feeding rates.
AB  - Aerobic anoxygenic photosynthesis (AAP) is found in an increasing number of
      proteobacterial strains thriving in ecosystems ranging from extremely
      oligotrophic to eutrophic. Here, we have investigated whether the fuel oxygenate
      degrading betaproteobacterium Aquincola tertiaricarbonis L108 can use AAP to
      compensate kinetic limitations at low heterotrophic substrate fluxes. In a
      fermenter experiment with complete biomass retention and also during chemostat
      cultivation, strain L108 was challenged with extremely low substrate feeding
      rates of tert-butyl alcohol (TBA), an intermediate of methyl tert-butyl ether
      (MTBE). Interestingly, formation of photosynthetic pigments, identified as
      bacteriochlorophyll a and spirilloxanthin, was only induced in growing cells at
      TBA feeding rates less than or equal to maintenance requirements observed under
      energy excess conditions. Growth continued at rates between 0.001 and 0.002 h(-1)
      even when the TBA feed was decreased to values close to 30 % of this maintenance
      rate. Partial sequencing of genomic DNA of strain L108 revealed a
      bacteriochlorophyll synthesis gene cluster (bchFNBHL) and photosynthesis
      regulator genes (ppsR and ppaA) typically found in AAP and other photosynthetic
      proteobacteria. The usage of light as auxiliary energy source enabling evolution
      of efficient degradation pathways for kinetically limited heterotrophic
      substrates and for lowering the threshold substrate concentration Smin at which
      growth becomes zero is discussed. 

PMID- 23873784
TI  - Compound(s) secreted by Lactobacillus casei strain Shirota YIT9029 irreversibly
      and reversibly impair the swimming motility of Helicobacter pylori and Salmonella
      enterica serovar Typhimurium, respectively.
AB  - We conducted experiments in order to examine whether the probiotic Lactobacillus
      casei strain Shirota YIT9029 (LcS) in vitro and in vivo antagonism of
      Helicobacter pylori and Salmonella, involves inhibition of the swimming motility
      of these pathogens. We report the irreversible inhibition of the swimming
      motility of H. pylori strain 1101 and reversible inhibition of Salmonella
      enterica serovar Typhimurium (S. Typhimurium) strain SL1344 by compound(s)
      secreted by LcS. In H. pylori 1101, irreversible inhibition results in the
      helical cells being progressively replaced by cells with 'c'-shaped and coccoid
      morphologies, accompanied by a loss of FlaA and FlaB flagellin expression. In S.
      Typhimurium SL1344, transient inhibition develops after membrane depolarization
      and without modification of expression of FliC flagellin. The inhibitory activity
      of strain LcS against both S. Typhimurium and H. pylori swimming motilities is
      linked with a small sized, heat-sensitive, and partially trypsin-sensitive,
      secreted compound(s), and needed the cooperation of the secreted membrane
      permeabilizing lactic acid metabolite. The inhibition of S. Typhimurium SL1344
      swimming motility leads to delayed cell entry into human enterocyte-like Caco
      2/TC7 cells and a strong decrease of cell entry into human mucus-secreting HT29
      MTX cells. 

PMID- 23873783
TI  - Bacterial interference with canonical NFkappaB signalling.
AB  - The human body is constantly challenged by a variety of commensal and pathogenic
      micro-organisms that trigger the immune system. Central in the first line of
      defence is the pattern-recognition receptor (PRR)-induced stimulation of the
      NFkappaB pathway, leading to NFkappaB activation. The subsequent production of
      pro-inflammatory cytokines and/or antimicrobial peptides results in recruitment
      of professional phagocytes and bacterial clearance. To overcome this, bacteria
      have developed mechanisms for targeted interference in every single step in the
      PRR-NFkappaB pathway to dampen host inflammatory responses. This review aims to
      briefly overview the PRR-NFkappaB pathway in relation to the immune response and
      give examples of the diverse bacterial evasion mechanisms including changes in
      the bacterial surface, decoy production and injection of effector molecules.
      Targeted regulation of inflammatory responses is needed and bacterial molecules
      developed for immune evasion could provide future anti-inflammatory agents. 

PMID- 23873785
TI  - Fatal neurological side-effects with necrosis of spinal cord following nelarabine
      treatment in a child with relapsed T-cell acute lymphoblastic leukemia.

PMID- 23873786
TI  - Rational design of benzotrithiophene-diketopyrrolopyrrole-containing donor
      acceptor polymers for improved charge carrier transport.
AB  - Two new donor-acceptor polymers containing benzo[2,1-b:3,4-b':5,6
      c'']trithiophene (BTT) as donor and diketopyrrolopyrrole (DPP) as acceptor are
      synthesized and applied in OFETs. By tuning the alkyl substituents of the
      polymers, a striking difference in packing order, thin-film arrangement, and
      charge carrier transport is observed. The polymer without substituents at the BTT
      exhibits a hole mobility two orders of magnitude higher than that with alkyl
      chains therein. 

PMID- 23873787
TI  - Grain boundary sliding in aluminum nano-bi-crystals deformed at room temperature.
AB  - Room-temperature uniaxial compressions of 900-nm-diameter aluminum bi-crystals,
      each containing a high-angle grain boundary with a plane normal inclined at 24
      degrees  to the loading direction, revealed frictional sliding along the boundary
      plane to be the dominant deformation mechanism. The top crystallite sheared off
      as a single unit in the course of compression instead of crystallographic slip
      and extensive dislocation activity, as would be expected. Compressive stress
      strain data of deforming nano bicrystals was continuous, in contrast to single
      crystalline nano structures that show a stochastic stress strain signature, and
      displayed a peak in stress at the elastic limit of ~ 176 MPa followed by gradual
      softening and a plateau centered around ~ 125 MPa. An energetics-based physical
      model, which may explain observed room-temperature grain boundary sliding, in
      presented, and observations are discussed within the framework of crystalline
      nano-plasticity and defect microstructure evolution.

PMID- 23873788
TI  - Enhancement of excess electron transfer efficiency in DNA containing a
      phenothiazine donor and multiple stable phenanthrenyl base pairs.
AB  - EET grown ohm: Excess electron transfer (EET) was observed within a DNA duplex
      containing pi-stacked phenothiazine as an electron donor, phenanthrenes as
      electron carriers and 5-bromouracil as an electron trap. Increasing the number of
      phenanthrenyl base pairs increased EET efficiency. 

PMID- 23873789
TI  - 3-hydroxykynurenine and other Parkinson's disease biomarkers discovered by
      metabolomic analysis.
AB  - Parkinson's disease (PD) biomarkers are needed to enhance therapeutics research
      and to understand PD pathogenesis. Methods that simultaneously measure hundreds
      of small molecular-weight compounds-metabolomic analysis-"fingerprint" disease
      specific alterations in individual compounds or metabolic pathways. Beyond a
      nontargeted search for PD biomarkers, we hypothesized that PD cerebrospinal fluid
      would show increased formation of the excitotoxin 3-hydroxykynurenine and
      diminished concentration of the antioxidant glutathione. Cerebrospinal fluid was
      collected at <4 hours postmortem from 48 pathologically-verified PD subjects and
      57 comparably-aged controls. Assays involved ultra-high-performance liquid and
      gas chromatography linked to mass spectrometry. We used univariate techniques to
      determine fold-changes in concentrations of biochemicals; false-discovery rates
      were calculated to exclude spurious findings. Data was modeled using a Support
      Vector Machine for analyzing compounds selected by Welch's t test. Classification
      accuracy was determined by cross-validation. Of 243 structurally-identified
      biochemicals,19 compounds differentiated PD from controls at a 20% false
      discovery level. In PD, mean 3-hydroxykynurenine concentration was increased by
      one-third, and mean oxidized glutathione was decreased by 40% (for each, P <
      .01). Four of the 19 compounds differentiating PD from controls were N-acetylated
      amino acids, suggesting a generalized alteration in N-acetylation activity. The
      Support Vector Machine classification model distinguished between groups at 83%
      sensitivity and 91% specificity for the learning data, and at 65% and 79% from
      cross-validation. In this study, the first for metabolomic profiling of PD
      cerebrospinal fluid, we found several novel biomarkers and offer new directions
      for recognizing disease-specific biochemical indicators. The findings support
      involvement of excitotoxicity and oxidative stress in the pathogenesis of PD.

PMID- 23873791
TI  - An investigation into the mechanical and aesthetic properties of new generation
      coated nickel-titanium wires in the as-received state and after clinical use.
AB  - BACKGROUND/OBJECTIVES: The purpose of this study was to compare the mechanical,
      structural, and aesthetic properties of two types of aesthetic coated nickel
      titanium (NiTi) wires compared with comparable regular NiTi wires in the as
      received state and after clinical use. MATERIALS/METHODS: Sixty one subjects were
      randomly assigned to four groups (N = 61), two groups of coated wires and two
      groups of comparable, non-coated controls (n = 15/group). The period in the mouth
      ranged from 4 to 12 weeks after insertion. In total, 121 wires (61 retrieved and
      60 as-received) were used in the study. The percentages of coating retention and
      loss were extrapolated from scans. A brief survey of five questions with three
      choices was given to all patients. Differential scanning calorimetry (DSC) and
      three-point bending tests were done on as-received and used wires. RESULTS: The
      surface characterization by the percentage of resin remaining indicated that most
      wires in both test groups lost a significant amount of coating. A patient survey
      indicated that this was a noticeable feature for patients. DSC analysis of the
      wires indicated that the metallurgical properties of the coated wires were not
      similar to the uncoated wires in the as-received condition. Three-point bending
      results indicate a wide variation in test results with large standard deviations
      among all the groups. LIMITATIONS: The extent of coating loss requires
      investigating, as do the biological properties of the detached coating.
      CONCLUSIONS: Both wires lost a significant amount of aesthetic coating after
      varying periods in the mouth. The metallurgical testing of these findings may
      indicate that these wires perform differently in the mouth.

PMID- 23873790
TI  - Psychosocial benefits of a novel mindfulness intervention versus standard support
      in distressed women with breast cancer.
AB  - OBJECTIVE: It is well documented that stress is associated with negative health
      outcomes in cancer patients. The purpose of this study was to assess the effects
      of a novel mindfulness intervention called mindfulness-based art therapy (MBAT)
      versus standard educational support, on indices of stress and quality of life in
      breast cancer patients with high stress levels. METHODS: A total of 191 women
      were enrolled, stratified by age and stress level, and randomized to receive
      either an 8-week MBAT intervention or a breast cancer educational support program
      of equal time and duration. Psychosocial stress was measured using the Symptoms
      Checklist-90-Revised, and quality of life was measured using the Medical Outcomes
      Study Short-Form Health Survey at baseline, immediately post-intervention, and at
      6 months. RESULTS: Results showed overall significant improvements in
      psychosocial stress and quality of life in both the MBAT and educational support
      groups immediately post-intervention; however, participants with high stress
      levels at baseline had significantly improved overall outcomes only in the MBAT
      group, both immediately post-intervention and at 6 months. In addition, at 6
      months follow-up, participants attending five or more sessions trended toward
      retaining treatment effects better in the MBAT than in the control group.
      Finally, black women and white women were similar in terms of how they benefited
      from the MBAT intervention, even though white participants tended to have higher
      educational level and marital status. CONCLUSIONS: In conclusion, MBAT is
      associated with significant, sustained benefits across a diverse range of breast
      cancer patients, particularly those with high stress levels.

PMID- 23873792
TI  - NMR spectroscopy of soluble protein complexes at one mega-dalton and beyond.

PMID- 23873793
TI  - Does the combination of hyperkalemia and KATP activation determine excitation
      rate gradient and electrical failure in the globally ischemic fibrillating heart?
AB  - Ventricular fibrillation (VF) in the globally ischemic heart is characterized by
      a progressive electrical depression manifested as a decline in the VF excitation
      rate (VFR) and loss of excitability, which occur first in the subepicardium (Epi)
      and spread to the subendocardium (Endo). Early electrical failure is detrimental
      to successful defibrillation and resuscitation during cardiac arrest.
      Hyperkalemia and/or the activation of ATP-sensitive K(+) (KATP) channels have
      been implicated in electrical failure, but the role of these factors in ischemic
      VF is poorly understood. We determined the VFR-extracellular K(+) concentration
      ([K(+)]o) relationship in the Endo and Epi of the left ventricle during VF in
      globally ischemic hearts (Isch group) and normoxic hearts subjected to
      hyperkalemia (HighK group) or a combination of hyperkalemia and the KATP channel
      opener cromakalim (HighK-Crom group). In the Isch group, Endo and Epi values of
      [K(+)]o and VFR were compared in the early (0-6 min), middle (7-13 min), and late
      (14-20 min) phases of ischemic VF. A significant transmural gradient in VFR (Endo
      > Epi) was observed in all three phases, whereas a significant transmural
      gradient in [K(+)]o (Epi > Endo) occurred only in the late phase of ischemic VF.
      In the Isch group, the VFR decrease and inexcitability started to occur at much
      lower [K(+)]o than in the HighK group, especially in the Epi. Combining KATP
      activation with hyperkalemia only shifted the VFR-[K(+)]o curve upward (an effect
      opposite to real ischemia) without changing the [K(+)]o threshold for asystole.
      We conclude that hyperkalemia and/or KATP activation cannot adequately explain
      the heterogeneous electrical depression and electrical failure during ischemic
      VF.

PMID- 23873794
TI  - beta3-Adrenergic receptor antagonist improves exercise performance in pacing
      induced heart failure.
AB  - In heart failure (HF), the impaired left ventricular (LV) arterial coupling and
      diastolic dysfunction present at rest are exacerbated during exercise. We have
      previously shown that in HF at rest stimulation of beta3-adrenergic receptors by
      endogenous catecholamine depresses LV contraction and relaxation. beta3
      Adrenergic receptors are activated at higher concentrations of catecholamine.
      Thus exercise may cause increased stimulation of cardiac beta3-adrenergic
      receptors and contribute to this abnormal response. We assessed the effect of L
      748,337 (50 MUg/kg iv), a selective beta3-adrenergic receptor antagonist (beta3
      ANT), on LV dynamics during exercise in 12 chronically instrumented dogs with
      pacing-induced HF. Compared with HF at rest, exercise increased LV end-systolic
      pressure (PES), minimum LV pressure (LVPmin), and the time constant of LV
      relaxation (tau) with an upward shift of early diastolic portion of LV pressure
      volume loop. LV contractility decreased and arterial elastance (EA) increased. LV
      arterial coupling (EES/EA) (0.40 vs. 0.51) was impaired. Compared with exercise
      in HF preparation, exercise after beta3-ANT caused similar increases in heart
      rate and PES but significantly decreased tau (34.9 vs. 38.3 ms) and LVPmin with a
      downward shift of the early diastolic portion of LV pressure-volume loop and
      further augmented dV/dtmax. Both EES and EES/EA (0.68 vs. 0.40) were increased.
      LV mechanical efficiency improved from 0.39 to 0.53. In conclusion, after HF,
      beta3-ANT improves LV diastolic filling; increases LV contractility, LV arterial
      coupling, and mechanical efficiency; and improves exercise performance.

PMID- 23873795
TI  - The beta-arrestin-biased ligand TRV120023 inhibits angiotensin II-induced cardiac
      hypertrophy while preserving enhanced myofilament response to calcium.
AB  - In the present study, we compared the cardioprotective effects of TRV120023, a
      novel angiotensin II (ANG II) type 1 receptor (AT1R) ligand, which blocks G
      protein coupling but stimulates beta-arrestin signaling, against treatment with
      losartan, a conventional AT1R blocker in the treatment of cardiac hypertrophy and
      regulation of myofilament activity and phosphorylation. Rats were subjected to 3
      wk of treatment with saline, ANG II, ANG II + losartan, ANG II + TRV120023, or
      TRV120023 alone. ANG II induced increased left ventricular mass compared with
      rats that received ANG II + losartan or ANG II + TRV120023. Compared with saline
      controls, ANG II induced a significant increase in pCa50 and maximum Ca(2+)
      activated myofilament tension but reduced the Hill coefficient (nH). TRV120023
      increased maximum tension and pCa50, although to lesser extent than ANG II. In
      contrast to ANG II, TRV120023 increased nH. Losartan blocked the effects of ANG
      II on pCa50 and nH and reduced maximum tension below that of saline controls. ANG
      II + TRV120023 showed responses similar to those of TRV120023 alone; compared
      with ANG II + losartan, ANG II + TRV120023 preserved maximum tension and
      increased both pCa50 and cooperativity. Tropomyosin phosphorylation was lower in
      myofilaments from saline-treated hearts compared with the other groups.
      Phosphorylation of cardiac troponin I was significantly reduced in ANG II +
      TRV120023 and TRV120023 groups versus saline controls, and myosin-binding protein
      C phosphorylation at Ser(282) was unaffected by ANG II or losartan but
      significantly reduced with TRV120023 treatment compared with all other groups.
      Our data indicate that TRV120023-related promotion of beta-arrestin signaling and
      enhanced contractility involves a mechanism promoting the myofilament response to
      Ca(2+) via altered protein phosphorylation. Selective activation of beta-arrestin
      dependent pathways may provide advantages over conventional AT1R blockers. 

PMID- 23873796
TI  - Inhibition of the late sodium current slows t-tubule disruption during the
      progression of hypertensive heart disease in the rat.
AB  - The treatment of heart failure (HF) is challenging and morbidity and mortality
      are high. The goal of this study was to determine if inhibition of the late Na(+)
      current with ranolazine during early hypertensive heart disease might slow or
      stop disease progression. Spontaneously hypertensive rats (aged 7 mo) were
      subjected to echocardiographic study and then fed either control chow (CON) or
      chow containing 0.5% ranolazine (RAN) for 3 mo. Animals were then restudied, and
      each heart was removed for measurements of t-tubule organization and Ca(2+)
      transients using confocal microscopy of the intact heart. RAN halted left
      ventricular hypertrophy as determined from both echocardiographic and cell
      dimension (length but not width) measurements. RAN reduced the number of myocytes
      with t-tubule disruption and the proportion of myocytes with defects in
      intracellular Ca(2+) cycling. RAN also prevented the slowing of the rate of
      restitution of Ca(2+) release and the increased vulnerability to rate-induced
      Ca(2+) alternans. Differences between CON- and RAN-treated animals were not a
      result of different expression levels of voltage-dependent Ca(2+) channel 1.2,
      sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, ryanodine receptor type 2,
      Na(+)/Ca(2+) exchanger-1, or voltage-gated Na(+) channel 1.5. Furthermore,
      myocytes with defective Ca(2+) transients in CON rats showed improved Ca(2+)
      cycling immediately upon acute exposure to RAN. Increased late Na(+) current
      likely plays a role in the progression of cardiac hypertrophy, a key pathological
      step in the development of HF. Early, chronic inhibition of this current slows
      both hypertrophy and development of ultrastructural and physiological defects
      associated with the progression to HF.

PMID- 23873797
TI  - HIF-1alpha in heart: protective mechanisms.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that
      directs many of the cellular responses to hypoxia. In these studies, we have used
      a mouse model containing a cardiac-specific, oxygen-stabilized, doxycycline (Dox)
      off regulated HIF-1alpha transgene to probe the role of HIF-1alpha in
      cardioprotection. Hearts used in these studies were derived from wild-type (WT),
      noninduced (Non-I), and 2 day (2D) and 6 day (6D) Dox-deprived mice. Whereas HIF
      1alpha protein is undetectable in WT mice, it is present in heart tissue of
      "noninduced" transgenic mice, presumably because of leakiness of the promoter
      construct. In mice denied Dox for 2 or 6 days, HIF-1alpha is overexpressed to a
      much greater extent than Non-I or WT animals, as expected. WT and HIF-1alpha
      expressing hearts (Non-I, 2D and 6D induced) were subjected to 30 min of
      ischemia, and functional recovery was measured upon reperfusion. Recovery of
      preischemic left ventricular developed pressure was 14% for WT, 67% for Non-I
      hearts, 64% for 2D-induced, and 62% for 6D-induced hearts. 6D-induced HIF hearts
      have increased preischemic glycogen reserves, higher glycogen synthase protein
      levels, and significantly higher lactic acid release during ischemia. 6D-induced
      HIF hearts were also better able to maintain ATP levels during ischemia compared
      with WT and Non-I hearts. Interestingly, Non-I hearts showed no significant
      increase in glycogen reserves, glycolytic flux, or greater ATP preservation
      during ischemia and yet were protected to a similar extent as the 6D-induced
      hearts. Finally, the mitochondrial membrane potential of isolated adult myocytes
      was monitored during anoxia or treatments with cyanide and 2-deoxyglucose. HIF
      1alpha expression was shown to protect mitochondrial polarization during both
      stress treatments. Taken together these data indicate that, while HIF-1alpha
      expression in heart does induce increases in compensatory glycolytic capacity,
      these changes are not necessarily required for cardioprotection, at least in this
      model of ischemic stress.

PMID- 23873798
TI  - Increased tissue transglutaminase activity contributes to central vascular
      stiffness in eNOS knockout mice.
AB  - Nitric oxide (NO) can modulate arterial stiffness by regulating both functional
      and structural changes in the arterial wall. Tissue transglutaminase (TG2) has
      been shown to contribute to increased central aortic stiffness by catalyzing the
      cross-linking of matrix proteins. NO S-nitrosylates and constrains TG2 to the
      cytosolic compartment and thereby holds its cross-linking function latent. In the
      present study, the role of endothelial NO synthase (eNOS)-derived NO in
      regulating TG2 function was studied using eNOS knockout mice. Matrix-associated
      TG2 and TG2 cross-linking function were higher, whereas TG2 S-nitrosylation was
      lower in the eNOS(-/-) compared with wild-type (WT) mice. Pulse-wave velocity
      (PWV) and blood pressure measured noninvasively were elevated in the eNOS(-/-)
      compared with WT mice. Intact aortas and decellularized aortic tissue scaffolds
      of eNOS(-/-) mice were significantly stiffer, as determined by tensile testing.
      The carotid arteries of the eNOS(-/-) mice were also stiffer, as determined by
      pressure-dimension analysis. Invasive methods to determine the PWV-mean arterial
      pressure relationship showed that PWV in eNOS(-/-) and WT diverge at higher mean
      arterial pressure. Thus eNOS-derived NO regulates TG2 localization and function
      and contributes to vascular stiffness.

PMID- 23873799
TI  - Serial measurement of hFABP and high-sensitivity troponin I post-PCI in STEMI:
      how fast and accurate can myocardial infarct size and no-reflow be predicted?
AB  - The objective of this study was to compare heart-specific fatty acid binding
      protein (hFABP) and high-sensitivity troponin I (hsTnI) via serial measurements
      to identify early time points to accurately quantify infarct size and no-reflow
      in a preclinical swine model of ST-elevated myocardial infarction (STEMI).
      Myocardial necrosis, usually confirmed by hsTnI or TnT, takes several hours of
      ischemia before plasma levels rise in the absence of reperfusion. We evaluated
      the fast marker hFABP compared with hsTnI to estimate infarct size and no-reflow
      upon reperfused (2 h occlusion) and nonreperfused (8 h occlusion) STEMI in swine.
      In STEMI (n = 4) and STEMI + reperfusion (n = 8) induced in swine, serial blood
      samples were taken for hFABP and hsTnI and compared with triphenyl tetrazolium
      chloride and thioflavin-S staining for infarct size and no-reflow at the time of
      euthanasia. hFABP increased faster than hsTnI upon occlusion (82 +/- 29 vs. 180
      +/- 73 min, P < 0.05) and increased immediately upon reperfusion while hsTnI
      release was delayed 16 +/- 3 min (P < 0.05). Peak hFABP and hsTnI reperfusion
      values were reached at 30 +/- 5 and 139 +/- 21 min, respectively (P < 0.05).
      Infarct size (containing 84 +/- 0.6% no-reflow) correlated well with area under
      the curve for hFABP (r(2) = 0.92) but less for hsTnI (r(2) = 0.53). At 50 and 60
      min reperfusion, hFABP correlated best with infarct size (r(2) = 0.94 and 0.93)
      and no-reflow (r(2) = 0.96 and 0.94) and showed high sensitivity for myocardial
      necrosis (2.3 +/- 0.6 and 0.4 +/- 0.6 g). hFABP rises faster and correlates
      better with infarct size and no-reflow than hsTnI in STEMI + reperfusion when
      measured early after reperfusion. The highest sensitivity detecting myocardial
      necrosis, 0.4 +/- 0.6 g at 60 min postreperfusion, provides an accurate and early
      measurement of infarct size and no-reflow.

PMID- 23873800
TI  - Short-term administration of progesterone and estradiol independently alter
      carotid-vasomotor, but not carotid-cardiac, baroreflex function in young women.
AB  - The individual effects of estrogen and progesterone on baroreflex function remain
      poorly understood. We sought to determine how estradiol (E2) and progesterone
      (P4) independently alter the carotid-cardiac and carotid-vasomotor baroreflexes
      in young women by using a hormone suppression and exogenous add-back design.
      Thirty-two young women were divided into two groups and studied under three
      conditions: 1) after 4 days of endogenous hormone suppression with a gonadotropin
      releasing hormone antagonist (control condition), 2) after continued suppression
      and 3 to 4 days of supplementation with either 200 mg/day oral progesterone (N =
      16) or 0.1 to 0.2 mg/day transdermal 17beta-estradiol (N = 16), and 3) after
      continued suppression and 3 to 4 days of supplementation with both hormones.
      Changes in heart rate (HR), mean arterial pressure (MAP), and femoral vascular
      conductance (FVC) were measured in response to 5 s of +50 mmHg external neck
      pressure to unload the carotid baroreceptors. Significant hormone effects on the
      change in HR, MAP, and FVC from baseline at the onset of neck pressure were
      determined using mixed model covariate analyses accounting for P4 and E2 plasma
      concentrations. Neither P4 (P = 0.95) nor E2 (P = 0.95) affected the HR response
      to neck pressure. Higher P4 concentrations were associated with an attenuated
      fall in FVC (P = 0.01), whereas higher E2 concentrations were associated with an
      augmented fall in FVC (P = 0.02). Higher E2 was also associated with an augmented
      rise in MAP (P = 0.01). We conclude that progesterone blunts whereas estradiol
      enhances carotid-vasomotor baroreflex sensitivity, perhaps explaining why no
      differences in sympathetic baroreflex sensitivity are commonly reported between
      low and high combined hormone phases of the menstrual cycle.

PMID- 23873802
TI  - Neonatal acute liver failure complicated by patent ductus venosus: diagnosis and
      management.

PMID- 23873801
TI  - Activation of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis
      attenuates the cardiac reactivity to acute emotional stress.
AB  - Recent data indicate the brain angiotensin-converting enzyme/ANG II/AT1 receptor
      axis enhances emotional stress responses. In this study, we investigated whether
      its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/ANG-(1
      7)/Mas axis, attenuate the cardiovascular responses to acute emotional stress. In
      conscious male Wistar rats, the tachycardia induced by acute stress (air jet 10
      l/min) was attenuated by intravenous injection of ANG-(1-7) [Delta heart rate
      (HR): saline 136 +/- 22 vs. ANG-(1-7) 61 +/- 25 beats/min; P < 0.05]. Peripheral
      injection of the ACE2 activator compound, XNT, abolished the tachycardia induced
      by acute stress. We found a similar effect after intracerebroventricular
      injections of either ANG-(1-7) or XNT. Under urethane anesthesia, the tachycardia
      evoked by the beta-adrenergic agonist was markedly reduced by ANG-(1-7) [DeltaHR:
      saline 100 +/- 16 vs. ANG-(1-7) 18 +/- 15 beats/min; P < 0.05]. The increase in
      renal sympathetic nerve activity (RSNA) evoked by isoproterenol was also
      abolished after the treatment with ANG-(1-7) [DeltaRSNA: saline 39% vs. ANG-(1-7)
      -23%; P < 0.05]. The tachycardia evoked by disinhibition of dorsomedial
      hypothalamus neurons, a key nucleus for the cardiovascular response to emotional
      stress, was reduced by ~45% after intravenous injection of ANG-(1-7). In
      cardiomyocyte, the incubation with ANG-(1-7) (1 MUM) markedly attenuated the
      increases in beating rate induced by isoproterenol. Our data show that activation
      of the ACE2/ANG-(1-7)/Mas axis attenuates stress-induced tachycardia. This effect
      might be either via the central nervous system reducing anxiety level and/or
      interfering with the positive chronotropy mediated by activation of cardiac beta
      adrenergic receptors. Therefore, ANG-(1-7) might contribute to reduce the
      sympathetic load to the heart during situations of emotional stress, reducing the
      cardiovascular risk.

PMID- 23873803
TI  - Dicopper(II) Metallacyclophanes with Electroswitchable Polymethyl-Substituted
      para-Phenylene Spacers.
AB  - Double-stranded anionic dinuclear copper(II) metallacyclic complexes of the
      paracyclophane type [Cu2L2](4-) have been prepared by the Cu(II)-mediated self
      assembly of different para-phenylenebis(oxamato) bridging ligands with either
      zero-, one-, or four-electron-donating methyl substituents (L=N,N'-para
      phenylenebis(oxamate) (ppba; 1), 2-methyl- N,N'-para-phenylenebis(oxamate)
      (Meppba; 2), and 2,3,5,6-tetramethyl- N,N'-para-phenylenebis(oxamate) (Me4ppba;
      3)). These complexes have been isolated as their tetra-n-butylammonium (1 a-3 a),
      lithium(I) (1 b-3 b), and tetraphenylphosphonium salts (1 c-3 c). The X-ray
      crystal structures of 1 a and 3 c show a parallel-displaced pi-stacked
      conformation with a smaller deviation from perpendicularity between the two
      benzene rings and the basal planes of the square planar Cu(II) ions when
      increasing the number of methyl substituents (average dihedral angles (phi) of
      58.72(7) and 73.67(5) degrees  for 1 a and 3 c, respectively). Variable
      temperature (2.0-300 K) magnetic-susceptibility measurements show an overall
      increase of the intramolecular antiferromagnetic coupling with the number of
      methyl substituents onto the para-phenylene spacers (-J=75-95, 100-124, and 128
      144 cm(-1) for 1 a-c, 2 a-c, and 3 a-c, respectively; H=-JS1*S2). Cyclic
      voltammetry (CV) measurements show a reversible one-electron oxidation of the
      double polymethyl-substituted para-phenylenediamidate bridging skeleton at a
      relatively low formal potential that decreases with the number of methyl
      substituents (E1=+0.33, +0.24, and +0.15 V vs. SCE for 1-3, respectively). The
      monooxidized dicopper(II) pi-radical cation species 3' prepared by the chemical
      oxidation of 3 with bromine exhibits intense metal-to-ligand charge-transfer
      (MLCT) transitions in the visible and near-IR (lambdamax=595 and 875 nm,
      respectively) regions together with a rhombic EPR signal with a seven-line
      splitting pattern due to hyperfine coupling with the nuclear spin of the two
      Cu(II) ions. Density functional (DF) calculations for 3' evidence a
      characteristic iminoquinonoid-type short-long-short alternating sequence of C-N
      and C-C bonds for both tetramethyl-para-phenylenediamidate bridges and a large
      amount of spin density of negative sign mainly delocalized along each of the four
      benzene C atoms directly attached to the amidate N atoms, which is in agreement
      with a fully delocalized pi-stacked monoradical ligand description. Hence, the
      spins of the two Cu(II) ions (SCu=1/2) that are antiparallel aligned in 3 (OFF
      state) become parallel in 3' (ON state). Further developments may be then
      envisaged for this new permethylated dicopper(II) paracyclophane with a redox
      noninnocent ligand as a prototype for molecular magnetic electroswitch.

PMID- 23873804
TI  - The changing incidence of primary central nervous system lymphoma is driven
      primarily by the changing incidence in young and middle-aged men and differs from
      time trends in systemic diffuse large B-cell non-Hodgkin's lymphoma.
AB  - There has been an overall decline in the United States incidence of Primary CNS
      Lymphoma (PCNSL) from 1998 to 2008. This study's intent was to characterize the
      cohorts contributing to it. First, calculated the PCNSL incidence rates from nine
      Surveillance, Epidemiology, and End Results (SEER) registries for time period
      1973 to 2008. Second, examined the time trends overall and by age and gender.
      Third, used 1992-2008 SEER data from the same registries to obtain overall trends
      for diffuse large B-cell lymphoma (DLBCL). Last, rates were age-adjusted to the
      2000 US standard population and reported per 100,000 person-years. Rates
      continued to increase in women at all ages and men aged 65 and older. In men aged
      20-39 and 40-64 years incidence rates peaked in 1995 and then declined
      dramatically, stabilizing after 1998. The trends in the incidence of PCNSL over
      this time frame were significantly different from DLBCL for ages 20-39 (P <
      0.001) and 40-64 (P < 0.001) years but were not different for the 65 years and
      older age group (P = 0.99). The overall PCNSL incidence rate declined since 1995
      and was driven primarily by the changing incidence in young and middle-aged men.
      The rate has continued to increase in men aged 65 years and older and in women.
      The trends in incidence in the younger age groups over this time period did not
      parallel those observed for DLBCL.

PMID- 23873805
TI  - Identification of different depressive symptoms after mastectomy.

PMID- 23873806
TI  - DNA terminal breathing regulated by metal ions for colloidal logic gates.

PMID- 23873807
TI  - Comparative evaluation of intestinal nitric oxide in embryonic zebrafish exposed
      to metal oxide nanoparticles.
AB  - Nanoparticle (NP) exposure may induce oxidative stress through generation of
      reactive oxygen and nitrogen species, which can lead to cellular and tissue
      damage. The digestive system is one of the initial organs affected by NP
      exposure. Here, it is demonstrated that exposure to metal oxide NPs induces
      differential changes in zebrafish intestinal NO concentrations. Intestinal NO
      concentrations are quantified electrochemically with a carbon fiber
      microelectrode inserted in the intestine of live embryos. Specificity of the
      electrochemical signals is demonstrated by NO-specific pharmacological
      manipulations and the results are correlated with the 4,5-diaminofluorescein
      diacetate (DAF-FM-DA). NPs are demonstrated to either induce or reduce
      physiological NO levels depending on their redox reactivity, type and dose. NO
      level is altered following exposure of zebrafish embryos to CuO and CeO2 NPs at
      various stages and concentrations. CuO NPs increase NO concentration, suggesting
      an intestinal oxidative damage. In contrast, low CeO2 NP concentration exposure
      significantly reduces NO levels, suggesting NO scavenging activity. However, high
      concentration exposure results in increased NO. Alterations in NO concentration
      suggest changes in intestinal physiology and oxidative stress, which will
      ultimately correspond to NPs toxicity. This work also demonstrates the use of
      electrochemistry to monitor in vivo changes of NO within zebrafish organs. 

PMID- 23873808
TI  - Temperature-independent hole mobility of a smectic liquid-crystalline
      semiconductor based on band-like conduction.
AB  - A liquid-crystalline (LC) phenylterthiophene derivative, which exhibited an
      ordered smectic phase at room temperature, was purified by vacuum sublimation
      under a flow of nitrogen. During the sublimation process, thin plates with sizes
      of 1 mm grew on the surface of the vacuum tube. The crystals exhibited the same X
      ray diffraction patterns as the ordered smectic phase of the LC state that was
      formed through a conventional recrystallization process by using organic
      solvents. Because of the removal of chemical impurities, the hole mobility in the
      ordered smectic phase of the vacuum-grown thin plates increased to 1.2*10(-1)
      cm(2) V(-1) s(-1) at room temperature, whereas that of the LC precipitates was
      7*10(-2) cm(2) V(-1) s(-1). The hole mobility in the ordered smectic phase of the
      vacuum-sublimated sample was temperature-independent between 400 and 220 K. The
      electric-field dependence of the hole mobility was also very small within this
      temperature range. The temperature dependence of hole mobility was well-described
      by the Hoesterey-Letson model. The hole-transport characteristics indicate that
      band-like conduction affected by the localized states, rather than a charge
      carrier-hopping mechanism, is a valid mechanism for hole transport in an ordered
      smectic phase.

PMID- 23873809
TI  - Efficient alpha-helix induction in a linear peptide chain by N-capping with a
      bridged-tricyclic diproline analogue.

PMID- 23873810
TI  - Parkinson's disease-cognitive rating scale: psychometrics for mild cognitive
      impairment.
AB  - Lack of validated data on cutoff scores for mild cognitive impairment (MCI) and
      sensitivity to change in predementia stages of Parkinson's disease (PD) limit the
      utility of instruments measuring global cognition as screening and outcome
      measures in therapeutic trials. Investigators who were blinded to PD-Cognitive
      Rating Scale (PD-CRS) scores classified a cohort of prospectively recruited,
      nondemented patients into a PD with normal cognition (PD-NC) group and a PD with
      MCI (PD-MCI) group using Clinical Dementia Rating (CDR) and the Mattis Dementia
      Rating Scale-2 (MDRS-2). The discriminative power of the PD-CRS for PD-MCI was
      examined in a representative sample of 234 patients (145 in the PD-NC group; 89
      in the PD-MCI group) and in a control group of 98 healthy individuals.
      Sensitivity to change in the PD-CRS score (the minimal clinically important
      difference was examined with the Clinical Global Impression of Change scale and
      was calculated with a combination of distribution-based and anchor-based
      approaches) was explored in a 6-month observational multicenter trial involving a
      subset of 120 patients (PD-NC, 63; PD-MCI, 57). Regression analysis demonstrated
      that PD-CRS total scores (P < 0.001) and age (P = 0.01) independently
      differentiated PD-NC from PD-MCI. Area under the receiver operating
      characteristic curve (AUC) analysis (AUC, 0.85; 95% confidence interval, 0.80
      0.90) indicated that a score <= 81 of 134 was the optimal cutoff point on the
      total score for the PD-CRS (sensitivity, 79%; specificity, 80%; positive
      predictive value, 59%; negative predictive value, 91%). A range of change from 10
      to 13 points on the PD-CRS total score was indicative of clinically significant
      change. These findings suggest that the PD-CRS is a useful tool to identify PD
      MCI and to track cognitive changes in nondemented patients with PD.

PMID- 23873811
TI  - Systematic review of birth prevalence of neural tube defects in India.
AB  - BACKGROUND: Neural tube defects are one of the most prevalent congenital
      anomalies. Data on the total birth prevalence, live birth and stillbirth
      prevalence of neural tube defects in India are lacking. The objective of this
      study is to conduct a systematic review of birth prevalence of neural tube
      defects in India and compare it with existing estimates. METHODS: A PubMed search
      identified 463 articles, of which 19 articles were eligible for inclusion in the
      review. Meta-analysis was used to estimate the overall birth prevalence of neural
      tube defects and to investigate the variation among studies identified by this
      review. RESULTS: The 19 articles reported a total of 308,387 births, among which
      1310 cases of neural tube defects were reported, giving an overall birth
      prevalence of 4.1 per 1000 (95% confidence interval [CI], 3.1-5.4). The live
      birth and stillbirth prevalence of neural tube defects was 1.3 per 1000 births
      (95% CI, 0.9-1.8) and 1.7 per 1000 births (95% CI, 0.7-4.0), respectively. Among
      the neural tube defects, the reported prevalence of anencephaly was highest at
      2.1 per 1000 births (95% CI, 1.6-2.8) followed by spina bifida at 1.9 per 1000
      births (95% CI, 1.4-2.7). CONCLUSION: The systematic review suggests that neural
      tube defects contribute to a significant number of live births and stillbirths in
      India, suggesting that preconception folic acid supplementation should be an
      essential element of reproductive health services.

PMID- 23873812
TI  - Knowledge and periconceptional use of folic acid for the prevention of neural
      tube defects in ethnic communities in the United Kingdom: systematic review and
      meta-analysis.
AB  - BACKGROUND: It is widely accepted that periconceptional supplementation with
      folic acid can prevent a significant proportion of neural tube defects (NTDs).
      The present study evaluated how folic acid knowledge and periconceptional use for
      NTD prevention varies by ethnicity in the United Kingdom (U.K.). METHODS: A
      literature search was conducted to identify studies that included assessment of
      folic acid knowledge or use in U.K. women of different ethnicities. Only research
      and referenced sources published after 1991, the year of the landmark Medical
      Research Council's Vitamin Study, were included. A meta-analysis was performed of
      studies that assessed preconceptional folic acid use in Caucasians and non
      Caucasians. RESULTS: Five studies met the inclusion criteria for assessment of
      knowledge and/or use of folic acid supplements in U.K. women including non
      Caucasians. The available evidence indicates that South Asians specifically have
      less knowledge and lower periconceptional use of folic acid than Caucasians; one
      study found that West Indian and African women also had lower folic acid uptake.
      A synthesis of results from three of the studies, in a meta-analysis, shows that
      Caucasians are almost three times more likely to take folic acid before
      conception than non-Caucasians. CONCLUSION: From the limited evidence available,
      U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower
      uptake of folic acid supplementation than Caucasians during the periconceptional
      period. Implementing targeted, innovative education campaigns together with a
      mandatory fortification policy, including the fortification of ethnic minority
      foods, will be required for maximum prevention of folic acid-preventable NTDs
      across different ethnic groups.

PMID- 23873813
TI  - Retrospective and prospective epidemiological studies of 1500 karyotyped
      spontaneous human abortions. 1975.

PMID- 23873814
TI  - Retrospective and prospective epidemiological studies of 1,500 karyotyped
      spontaneous human abortions.

PMID- 23873815
TI  - Exploring the potential to use data linkage for investigating the relationship
      between birth defects and prenatal alcohol exposure.
AB  - BACKGROUND: This study explores the potential of data linkage to investigate the
      proportion of birth defects classified as alcohol-related (ARBD) by the
      Institutes of Medicine (IOM) that are attributable to maternal alcohol-use
      disorder. METHODS: Maternal alcohol-use disorder was identified using
      International Classification of Diseases (9th and 10th revision) codes for
      alcohol-related diagnoses recorded on record-linked Western Australian health,
      mental health, and/or drug and alcohol datasets 1983 to 2007. Children of these
      mothers (n=23,859) were compared with a randomly selected cohort of children born
      to mothers without an alcohol diagnosis, frequency-matched by maternal age,
      Aboriginal status, and child's birth year (n=61,370). Birth defects were
      identified through linkage with the Western Australian Register of Developmental
      Anomalies and defects with chromosomal causes were excluded. Associations between
      overall and individual IOM-designated ARBD and a maternal alcohol-related
      diagnosis recorded "during pregnancy" or "any" diagnosis (before/during/after
      pregnancy) was assessed using multivariate logistic regression to generate odds
      ratios and 95% confidence intervals. Population-attributable fractions were
      calculated for significant results using total population numbers. RESULTS: There
      was a significant association between maternal alcohol-related diagnoses recorded
      during pregnancy and ARBD (adjusted odds ratio, 3.14; 95% confidence interval,
      2.49-3.96), with an attributable fraction of 0.57%. "Any" maternal alcohol
      diagnosis demonstrated a higher attributable fraction for ARBD (1.53%), with the
      highest attributable fractions for microcephaly (7.31%), ptosis (3.75%), atrial
      septal defect (2.86%), and conotruncal heart defects (2.01%). CONCLUSION:
      Research using linked, population-based administrative health data has the
      potential to advance knowledge of ARBD. Routine collection and recording of
      alcohol use during pregnancy for all pregnant women is required and would enhance
      this methodology. Birth Defects Research (Part A) 97:497-504, 2013. (c) 2013
      Wiley Periodicals, Inc.

PMID- 23873816
TI  - Development of an improved rhodium catalyst for z-selective anti-markovnikov
      addition of carboxylic acids to terminal alkynes.
AB  - To develop more active catalysts for the rhodium-catalyzed addition of carboxylic
      acids to terminal alkynes furnishing anti-Markovnikov Z enol esters, a thorough
      study of the rhodium complexes involved was performed. A number of rhodium
      complexes were characterized by NMR, ESI-MS, and X-ray analysis and applied as
      catalysts for the title reaction. The systematic investigations revealed that the
      presence of chloride ions decreased the catalyst activity. Conversely, generating
      and applying a mixture of two rhodium species, namely, [Rh(DPPMP)2][H(benzoate)2]
      (DPPMP=diphenylphosphinomethylpyridine) and [{Rh(COD)(MU2-benzoate)}2], provided
      a significantly more active catalyst. Furthermore, the addition of a catalytic
      amount of base (Cs2CO3) had an additional accelerating effect. This higher
      catalyst activity allowed the reaction time to be reduced from 16 to 1-4 h while
      maintaining high selectivity. Studies on the substrate scope revealed that the
      new catalysts have greater functional-group compatibility.

PMID- 23873817
TI  - Lower sodium intake reduces blood pressure in adults and children, but is not
      associated with a reduced risk of all CVD or all cause mortality.

PMID- 23873818
TI  - Determinants for success rates of temporary anchorage devices in orthodontics: a
      meta-analysis (n > 50).
AB  - INTRODUCTION: The aim of this study was to review the literature and evaluate the
      failure rates and factors that affect the stability and success of temporary
      anchorage devices (TADs) used as orthodontic anchorage. METHODS: Data were
      collected from electronic databases: MEDLINE database, Scopus, and Web of
      Knowledge. Four combinations of term were used as keywords: screw orthodontic
      failure, screw orthodontic success, implant orthodontic failure, and implant
      orthodontic success. The following selection criteria were used to select
      appropriate articles: articles on implants and screws used as orthodontic
      anchorage, data only from human subjects, studies published in English, studies
      with more than 50 implants/screws, and both prospective and retrospective
      clinical studies. RESULTS: The search provided 209 abstracts about TADs used as
      anchorage. After reading and applying the selection criteria, 26 articles were
      included in the study. The data obtained were divided into two topics: which
      factors affected TAD success and to what degree and in how many articles they
      were quoted. Clinical factors were divided into three main groups: patient
      related, implant-related, and management-related factors. CONCLUSIONS: Although
      all articles included in this meta-analysis reported success rates of greater
      than 80 per cent, the factors determining success rates were inconsistent between
      the studies analysed and this made conclusions difficult.

PMID- 23873819
TI  - Expanding the spectrum of inflammatory spinal disease: AS it was, as it is now.

PMID- 23873821
TI  - Impaired quality of life, disability and mental health in Takayasu's arteritis.
AB  - OBJECTIVE: Patient-reported outcomes (PROs) are increasingly accepted to be among
      the major tools for outcome assessment in rheumatic disorders. In this study we
      aimed to assess quality of life (QoL), disability, anxiety and depression in
      patients with Takayasu's arteritis (TAK). METHODS: Patients followed with the
      diagnosis of TAK (n = 165) and healthy controls (HCs) (n = 109) were enrolled to
      the study. The 36-item Short Form Health Survey (SF-36) and hospital anxiety and
      depression scales (HADS) were used to assess QoL and mental status together with
      HAQ for disability. RESULTS: In SF-36 subscale assessment, all items were
      observed to be statistically lower in TAK patients; similarly HAQ scores were
      also higher (P < 0.001) in this group. In mental assessment, anxiety was found to
      be more common in TAK patients [90 (54.5%) vs 38 (34.9%), P = 0.001]. Depression
      also tended to be higher in TAK patients [70 (66.7%) vs 35 (33.3%)], without
      reaching significance (P = 0.086). Most of the SF-36 subgroup parameters were
      lower in TAK patients with active disease. Patients having anxiety and depression
      or with high HAQ scores reported worse SF-36 scores. In multivariate analysis,
      HADS-A, HADS-D and HAQ were associated with most SF-36 subscales. CONCLUSION:
      PROs demonstrate that not only general health but also physical and social
      functioning with physical role limitations and mental health parameters were
      impaired in TAK. Our results, especially in active disease, suggest that PROs
      such as SF-36 can be core domains of disease assessment in TAK, similar to ANCA
      associated vasculitides.

PMID- 23873820
TI  - Biologic treatment response among adults with juvenile idiopathic arthritis:
      results from the British Society for Rheumatology Biologics Register.
AB  - OBJECTIVE: To describe the use of and response to biologic therapies commenced in
      adults with JIA. METHODS: Patients with arthritis onset <16 years were identified
      from the British Society for Rheumatology Biologics Register for rheumatoid
      arthritis (BSRBR-RA) and stratified into ILAR JIA subtypes. Patterns of biologic
      use and treatment persistence were explored, with disability levels (HAQ) and
      remission rates [28-Joint Disease Activity Score (DAS28)] evaluated at 6 and 12
      months. RESULTS: Arthritis with an onset of <16 years was confirmed in 225
      patients and the ILAR subtype was determined in 154 (68%). Only 58 (26%) patients
      had a diagnosis of JIA recorded in the BSRBR-RA. The median age at biologic
      commencement was 31 years [interquartile range (IQR) 23-39] and 76% were female.
      The biologic therapies were etanercept (49%), infliximab (28%), adalimumab (22%)
      and anakinra (1%). Fifty per cent of patients received more than one biologic
      during follow-up (2 agents, n = 64; >=3 agents, n = 49). Treatment persistence at
      1 year was 78% (95% CI 71%, 82%), falling to 42% (95% CI 34%, 49%) at 5 years.
      Both the HAQ and DAS28 improved significantly at 6 months, with 21% and 28% of
      patients in remission (DAS28 < 2.6) at 6 and 12 months, respectively. CONCLUSION:
      This study describes patterns and identifies outcomes of biologic use in a
      national cohort of adults with JIA. With no national guidance currently available
      in this area, the choice of first biologic was inconsistent, although treatment
      outcomes were good. These data confirm that biologic therapies are an important
      treatment option in adults with active JIA in adulthood.

PMID- 23873822
TI  - Association of Takayasu arteritis with HLA-B 67:01 and two amino acids in HLA-B
      protein.
AB  - OBJECTIVE: Takayasu arteritis (TAK) is a rare autoimmune arteritis that affects
      large arteries. Although the association between TAK and HLA-B 52:01 is
      established, the other susceptibility HLA-B alleles are not fully known. We
      performed genetic association studies to determine independent HLA-B
      susceptibility alleles other than HLA-B 52:01 and to identify important amino
      acids of HLA-B protein in TAK susceptibility. METHODS: One hundred patients with
      TAK and 1000 unrelated healthy controls were genotyped for HLA-B alleles in the
      first set, followed by a replication set containing 73 patients with TAK and 1000
      controls to compare the frequencies of HLA-B alleles. Step-up logistic regression
      analysis was performed to identify susceptibility amino acids of HLA-B protein.
      RESULTS: Strong associations of susceptibility to TAK with HLA-B 52:01 and HLA-B
      67:01 were observed (P = 1.0 * 10(-16) and 9.5 * 10(-6), respectively). An
      independent susceptibility effect of HLA-B 67:01 from HLA-B 52:01 was also
      detected (P = 1.8 * 10(-7)). Amino acid residues of histidine at position 171 and
      phenylalanine at position 67, both of which are located in antigen binding
      grooves of the HLA-B protein, were associated with TAK susceptibility (P <= 3.8 *
      10(-5)) with a significant difference from other amino acid variations (DeltaAIC
      >= 9.65). CONCLUSION: HLA-B 67:01 is associated with TAK independently from HLA-B
      52:01. Two amino acids in HLA-B protein are strongly associated with TAK
      susceptibility.

PMID- 23873823
TI  - Darbepoetin-alfa and intravenous iron administration after autologous
      hematopoietic stem cell transplantation: a prospective multicenter randomized
      trial.
AB  - We conducted a randomized study analyzing the impact of darbepoetin alfa (DA)
      administration with or without intravenous (i.v.) iron on erythroid recovery
      after autologous hematopoietic cell transplantation (HCT). Patients were
      randomized between no DA (Arm 1), DA 300 MUg every 2 weeks starting on Day 28
      after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3).
      The proportion achieving complete hemoglobin (Hb) response within 18 weeks
      (primary end point) was 21% in Arm 1 (n = 24), 79% in Arm 2 (n = 25), and 100% in
      Arm 3 (n = 23; P < 0.0001). Erythropoietic response was shown to be significantly
      higher in Arm 3 (n = 46) than in Arm 2 (n = 50; P = 0.008), resulting in lower DA
      use, reduced drug costs, and improved quality of life scores, but the effect on
      transfusions was not significant. In multivariate analysis, DA administration (P
      < 0.0001), i.v. iron administration (P = 0.0010), high baseline Hb (P < 0.0001),
      and low baseline creatinine (P = 0.0458) were independently associated with
      faster achievement of complete Hb response. In conclusion, DA is highly effective
      to ensure full erythroid reconstitution after autologous HCT when started on Day
      28 post-transplant. I.v. iron sucrose further improves erythroid recovery.

PMID- 23873824
TI  - Appearance concerns among women with neurofibromatosis: examining sexual/bodily
      and social self-consciousness.
AB  - OBJECTIVE: Neurofibromatosis (NF) 1 and 2 have distinct appearance effects, yet
      little research has examined patients' appearance concerns. We assessed
      appearance concerns and self-consciousness, self-esteem, and loneliness among
      women with NF. METHODS: Women with NF1 (n = 79) and NF2 (n = 48) completed the
      Derriford Appearance Scale to assess appearance concerns and sexual/bodily and
      social self-consciousness, Rosenberg Self-Esteem Scale, and UCLA Loneliness
      Scale. Women's appearance concerns were coded to determine whether they were NF
      related and whether psychosocial factors contributed to the concerns. RESULTS: A
      total of 85% of women reported appearance concerns, many of which were NF-related
      and attributed to psychosocial factors. Women with NF1 reported significantly
      more sexual/bodily self-consciousness but similar levels of social self
      consciousness compared with women with NF2. Significantly higher sexual/bodily
      self-consciousness was found among married/cohabiting women regardless of NF
      group. Compared with general population norms and breast cancer survivors (BCS),
      women with NF1 reported significantly greater sexual/bodily and social self
      consciousness. Women with NF2 reported less sexual/bodily self-consciousness
      compared with population norms, yet tended to report greater sexual/bodily self
      consciousness than BCS. Women with NF2 reported significantly greater social self
      consciousness compared with population norms and BCS. For both NF1 and NF2,
      higher levels of sexual/bodily and social self-consciousness were related to
      lower self-esteem and higher levels of social self-consciousness to more
      loneliness. CONCLUSIONS: Appearance concerns are prevalent, and social self
      consciousness is high, among women with NF1 and NF2. Women with NF1 compared with
      NF2 experience more sexual/bodily self-consciousness. Providers should assess the
      impact of NF on women's self-perceptions and address sexual, body image, and
      social concerns.

PMID- 23873825
TI  - Synthesis of azahelicene N-oxide by palladium-catalyzed direct C-H annulation of
      a pendant (Z)-bromovinyl side chain.
AB  - Driving benzene round the twist: Azahelicene derivatives were synthesized in high
      yields by utilizing palladium-catalyzed C-H annulation reactions.
      Functionalization at the C5 position in 6-azahelicene by using palladium
      catalyzed C-H arylation also gave coupling products in good yields. A tandem
      intra- and intermolecular double C-H coupling reaction was performed to give a
      functionalized helicene in a one-pot procedure.

PMID- 23873827
TI  - Influence of the metal ion on the two-photon absorption properties of lanthanide
      complexes including near-IR emitters.
AB  - The synthesis of tris(2-thenoyltrifluoroacetonate)lanthanide(III) complexes
      featuring a diethylaminostyryl-2,2'-bipyridine coligand was achieved for
      lanthanum; the near-infrared (NIR) emitters neodymium, erbium, and ytterbium; and
      the transition-metal yttrium. The photophysical properties were thoroughly
      studied, and it was demonstrated that the conjugated bipyridine ligand acts as a
      good antenna for the sensitization of the NIR emitters. The two-photon absorption
      (TPA) properties of all five complexes were investigated by using both two-photon
      excited fluorescence and the Z-scan method. We demonstrate that the nature of the
      rare earth ion has almost no influence on the TPA properties centered on the
      conjugated bipyridyl ligand. Finally, we show that Yb(III) is sensitized by a two
      photon antenna effect, and that Nd(III) is mostly sensitized by a one-photon
      process involving direct excitation of forbidden f-f transitions. 

PMID- 23873826
TI  - Nanoparticle-programmed self-destructive neural stem cells for glioblastoma
      targeting and therapy.
AB  - A 3-step glioblastoma-tropic delivery and therapy method using nanoparticle
      programmed self-destructive neural stem cells (NSCs) is demonstrated in vivo: 1)
      FDA-approved NSCs for clinical trials are loaded with pH-sensitive MSN-Dox; 2)
      the nanoparticle conjugates provide a delayed drug-releasing mechanism and allow
      for NSC migration towards a distant tumor site; 3) NSCs eventually undergo cell
      death and release impregnated MSN-Dox, which subsequently induces toxicity
      towards surrounding glioma cells. 

PMID- 23873828
TI  - Therapeutic challenges in treating patients with fragile X syndrome and
      neoplasia.
AB  - The administration of cytotoxic therapy to patients with fragile X syndrome (FXS)
      presents several unique therapeutic challenges. The existence of fragile sites
      poses a theoretical risk of tumorigenesis and potentially increased treatment
      associated toxicity, however, controversy exists. We review the 42 previously
      reported cases of neoplasia in patients with FXS and report two novel neoplasms
      in patients treated with radiation therapy or combined chemoradiation. Our
      experience suggests that radiation therapy can be delivered safely in these
      patients without an expectation for increased acute/sub-acute normal tissue
      toxicity; however, treatment requires specialized facilities with the resources
      to deliver this care safely.

PMID- 23873829
TI  - Flexibly tethered dinuclear zinc complexes: a solution to the entropy problem in
      CO2/epoxide copolymerization catalysis?

PMID- 23873830
TI  - Modelling suggests authentic leadership from managers influences structural
      empowerment, job satisfaction and self-rated performance among nurses.

PMID- 23873831
TI  - Thrombin generation and procoagulant phospholipids in patients with essential
      thrombocythemia and reactive thrombocytosis.
AB  - Thrombocytosis is a commonly encountered clinical scenario and can be either a
      secondary process (reactive thrombocytosis), or due to clonal disorder (i.e.,
      essential thrombocythemia). This distinction is important as it carries
      implications for evaluation, prognosis and treatment. In this study we compared
      procoagulant potential in essential thrombocythemia and reactive thrombocytosis
      by measuring the thrombin generation and the level of circulating procoagulant
      phospholipids with functional tests. Twenty nine patients with essential
      thrombocythemia and 24 with reactive thrombocytosis were studied. Thrombin
      generation was determined by calibrated automated thrombography. Procoagulant
      phospholipids were detected by a chronometric standardised method (STA-Procoag
      PPL). Patients with reactive thrombocytosis had a longer lag time, higher
      endogenous thrombin potential, peak of thrombin generation and velocity index
      than patients with essential thrombocythemia. The level of circulating
      procoagulant phospholipids was increased in patients with essential
      thrombocythemia as observed with the procoagulant phospholipids assay. Each
      parameter was analysed using ROC curves. Highest areas under the curve (AUC) were
      found for lag time and procoagulant phospholipids ratio (0.817 and 0.853,
      respectively), associated with high negative predictive value for ET (92.3% and
      80%, respectively). In conclusion, patients with essential thrombocythemia and
      reactive thrombocytosis displayed significant differences in terms of thrombin
      generation and levels of procoagulant phospholipids. Among these parameters, lag
      time and procoagulant phospholipids ratio could help to differentiate between
      reactive thrombocytosis and essential thrombocythemia patients.

PMID- 23873832
TI  - P21-activated kinase 4 regulates the cyclin-dependent kinase inhibitor p57(kip2)
      in human breast cancer.
AB  - The p21-activated kinases have been implicated in the control of cell cycle
      progression. However, the biological mechanism underlying the role of p21
      activated kinase 4 (PAK4) in cell cycle control remains unknown. Here, by using
      quantitative RT-PCR and immunoblot analyses, we discovered that over-expression
      of PAK4 could suppress cyclin-dependent kinase inhibitor 1C (p57(Kip2) )
      expression in the MCF-7 human breast cancer cell line, whereas lentiviral vector
      mediated small interfering RNA (siRNA) knockdown of PAK4 markedly promoted
      p57(Kip2) expression in MCF-7 cells. Furthermore, PAK4-mediated down-regulation
      of p57(Kip2) was reversed by MG132, a specific proteasome inhibitor. The
      ubiquitination assay confirmed that the activity of PAK4 attenuated p57(Kip2)
      protein stability through the ubiquitin-proteasome pathway in MCF-7 cells.
      Moreover, a significant inverse correlation between PAK4 and p57(Kip2) protein
      levels was observed in breast cancer tissues by immunohistochemical analysis.
      Taken together, our data demonstrate a novel function for PAK4 in regulating the
      stability of p57(Kip2) , possibly through the ubiquitin-proteasome pathway,
      leading to increased proliferation of breast cancer cells. Thus, PAK4 may be used
      as a potential diagnostic and therapeutic target for human breast cancer.

PMID- 23873834
TI  - A new proton conductive liquid with no ions: pseudo-protic ionic liquids.
AB  - Liquids with no ions! Raman analysis and quantum calculations suggest that
      electrically neutral molecular species predominantly exist in an N
      methylimidazole and acetic acid equimolar mixture, and that ionic species are
      rather minor. Nevertheless, the mixture has significant ionic conductivity, and
      shows "good ionic" or "superionic" behavior (see figure). It may be suitable to
      call such liquids "pseudo-ionic liquids" rather than "ionic liquids".

PMID- 23873833
TI  - Biochemistry of the tale transcription factors PREP, MEIS, and PBX in
      vertebrates.
AB  - TALE (three amino acids loop extension) homeodomain transcription factors are
      required in various steps of embryo development, in many adult physiological
      functions, and are involved in important pathologies. This review focuses on the
      PREP, MEIS, and PBX sub-families of TALE factors and aims at giving information
      on their biochemical properties, i.e., structure, interactors, and interaction
      surfaces. Members of the three sets of protein form dimers in which the common
      partner is PBX but they can also directly interact with other proteins forming
      higher-order complexes, in particular HOX. Finally, recent advances in
      determining the genome-wide DNA-binding sites of PREP1, MEIS1, and PBX1, and
      their partial correspondence with the binding sites of some HOX proteins, are
      reviewed. These studies have generated a few general rules that can be applied to
      all members of the three gene families. PREP and MEIS recognize slightly
      different consensus sequences: PREP prefers to bind to promoters and to have PBX
      as a DNA-binding partner; MEIS prefers HOX as partner, and both PREP and MEIS
      drive PBX to their own binding sites. This outlines the clear individuality of
      the PREP and MEIS proteins, the former mostly devoted to basic cellular
      functions, the latter more to developmental functions.

PMID- 23873835
TI  - Antibody conjugated PLGA nanoparticles for targeted delivery of paclitaxel
      palmitate: efficacy and biofate in a lung cancer mouse model.
AB  - Aberrant signaling of the epidermal growth factor receptor (EGFR) is common to a
      variety of human cancers and is also found to be over-expressed in most cases of
      non-small cell lung cancer. For the development of a molecularly targeted
      therapy, cetuximab-conjugated nanoparticles (immunonanoparticles, INPs) are
      designed and loaded with the lipophilic paclitaxel palmitate (pcpl) prodrug.
      Oleyl cysteineamide (OCA) is synthesized whereby its amphiphilic nature enables
      interfacial anchoring and thiol surface functionalization of PLGA NPs,
      facilitating bioconjugation to cetuximab by thioether bonds. It is demonstrated
      that the in vitro targeting efficiency and improved cellular internalization and
      cytotoxicity of this targeted delivery system in lung cancer cells over
      expressing EGFR. A quantitative measure of the high binding affinity of INPs to
      EGFR is demonstrated using surface plasmon resonance. In vivo tolerability and
      enhanced efficacy of cetuximab pcpl INPs in a metastatic lung cancer model are
      reported. Its therapeutic efficacy in A549-luc-C8 lung tumors is shown using non
      invasive bioluminescent imaging. Intravenous administration of cetuximab pcpl
      INPs to mice results in significantly higher inhibition of tumor growth and
      increased survival rates as compared to the non-targeted drug solution, drug
      loaded nanoparticles or blank INPs. Pharmacokinetics and organ biodistribution of
      the prodrug and parent drug are evaluated by LC-MS/MS in lung tumor bearing mice.
      No enhanced total accumulation of nanoparticles or INPs is found at the tumor
      tissue. However, persistent pcpl levels with sustained conversion and release of
      paclitaxel are observed for the encapsulated prodrug possibly suggesting the
      formation of a drug reservoir. The overall results indicate the potential of this
      promising targeted platform for the improved treatment of lung cancer and other
      EGFR positive tumors. 

PMID- 23873836
TI  - Novel biomimetic thermosensitive beta-tricalcium phosphate/chitosan-based
      hydrogels for bone tissue engineering.
AB  - Among the less invasive surgical procedures for tissue engineering application,
      injectable in situ gelling systems have gained great attention. In this contest,
      this article is aimed to realize thermosensitive chitosan-based hydrogels,
      crosslinked with beta-glycerophosphate and reinforced via physical interactions
      with beta-tricalcium phosphate. The kinetics of sol-gel transition and the
      composite hydrogel properties were investigated by rheological analysis. The
      hydrogels were also characterized by Fourier transform infrared study, X-ray
      diffraction, scanning electron microscopy, transmission electron microscopy
      analysis, and thermal and biological studies. The hydrogels exhibit a gel-phase
      transition at body temperature, and a three-dimensional network with typical
      rheological properties of a strong gel. The presence of the inorganic phase, made
      up of nanocrystals, provides a structure with chemico-physical composition that
      mimics natural bone tissue, favoring cellular activity. These findings suggest
      the potential of the materials as promising candidates for hard tissue
      regeneration.

PMID- 23873837
TI  - Optical control of TRPV1 channels.

PMID- 23873838
TI  - Downregulation of cytochrome P450scc as an initial adverse effect of adult
      exposure to diethylstilbestrol on testicular steroidogenesis.
AB  - Reproductive toxicities and endocrine disruptions caused by chemicals in adult
      males are still poorly understood. It is our objectives to understand further
      details of the initial adverse effects leading severe testicular toxicities of a
      pharmaceutical endocrine disruptor, diethylstilbestrol (DES). Downregulations of
      both testicular regulatory proteins, such as the steroidogenic acute regulatory
      protein (StAR) and the peripheral benzodiazepine receptor (PBR), which play
      important roles in the transport of cholesterol into the mitochondria, and
      cytochrome P450 mediating the cholesterol side chain cleavage reaction (P450scc),
      were observed in the rat orally administered DES (340 MUg/kg/2 days) for 2 weeks.
      We found that after only 1 week treatment with DES, the blood and testicular
      testosterone (TS) levels were drastically decreased without abnormalities of the
      StAR and PBR; however, the protein and mRNA levels of P450scc were diminished.
      Decrease in the conversion rate of cholesterol to pregnenolone was delayed in the
      in vitro assay using the testicular mitochondrial fraction from the rat treated
      with DES for 1 week. When the precursors in TS biosynthesis containing the testis
      were identified and determined by liquid chromatography-mass spectrometry
      analysis, decreased levels of all precursors except cholesterol were observed. In
      conclusion, suppressed cytochrome P450scc expression in adult male rat was
      identified as an initial target of DES in testicular steroidogenesis disorder
      leading reproductive toxicities.

PMID- 23873839
TI  - Synthesis and biological evaluation of a novel series of 6,8-dibromo
      4(3H)quinazolinone derivatives as anticancer agents.
AB  - Three novel series of 6,8-dibromo-4(3H)quinazolinone derivatives were
      synthesized. Some of the novel quinazolinone derivatives were tested for their
      antitumor activity against the human breast carcinoma cell line MCF-7. Compounds
      XIIIb, IX, XIVd, XIVb, XIVe, XIIIa, XIVc, XVc, and XIVa exerted powerful
      cytotoxic effects against the MCF7 cells, with very low IC50 values compared to
      doxorubicin (positive control). The IC50 values were 1.7, 1.8, 1.83, 5.4, 6.84,
      10.8, 13.9, 15.7, and 29.6 ug/mL, respectively. 

PMID- 23873840
TI  - Laser-mediated cell ablation during post-implantation mouse development.
AB  - BACKGROUND: Laser-mediated cell ablation is a powerful tool that has been used to
      understand cell fate in a variety of externally developing organisms but has not
      been used during mammalian post-implantation development. RESULTS: We describe a
      method pairing laser ablation with murine embryo culture and establish parameters
      that can be used to precisely ablate cells in the selected field with minimal
      disruption to adjacent cells or the underlying cell matrix. Ablation of a large
      domain of endoderm, followed by ~1 day of culture results in a phenotypically
      normal embryo and gut tube, indicating that laser ablation is compatible with
      normal development. We next focused on one of the three precursor populations
      that have been shown to produce the liver bud. Ablations of a single progenitor
      domain result in a unilateral delay in the liver bud while the contralateral side
      is unaffected. CONCLUSIONS: We demonstrate that laser ablation is a specific and
      useful technique for studying cell fate in the mouse embryo. This method
      represents a powerful advance in developmental studies in the mouse and can be
      used to provide information on the specification of organs, differentiation, cell
      migration, and vital tissue interactions during development.

PMID- 23873841
TI  - Effect of unilateral diaphragmatic paralysis on postpneumonectomy lung growth.
AB  - Respiratory muscle-associated stretch has been implicated in normal lung
      development (fetal breathing movements) and postpneumonectomy lung growth. To
      test the hypothesis that mechanical stretch from diaphragmatic contraction
      contributes to lung growth, we performed left phrenic nerve transections (PNT) in
      mice with and without ipsilateral pneumonectomy. PNT was demonstrated by
      asymmetric costal margin excursion and confirmed at autopsy. In mice with two
      lungs, PNT was associated with a decrease in ipsilateral lung volume (P<0.05) and
      lung weight (P<0.05). After pneumonectomy, PNT was not associated with a change
      in activity level, measureable hypoxemia, or altered minute ventilation; however,
      microCT scanning demonstrated altered displacement and underinflation of the
      cardiac lobe within the first week after pneumonectomy. Coincident with the
      altered structural realignment, lung impedance measurements, fitted to the
      constant-phase model, demonstrated elevated airway resistance (P<0.05), but
      normal peripheral tissue resistance (P>0.05). Most important, PNT appeared to
      abrogate compensatory lung growth after pneumonectomy; the weight of the lobes of
      the right lung was significantly less than pneumonectomy alone (P<0.001) and
      indistinguishable from nonsurgical controls (P>0.05). We conclude that the cyclic
      stretch associated with diaphragmatic muscle contraction is a controlling factor
      in postpneumonectomy compensatory lung growth.

PMID- 23873843
TI  - Sustained inflation at birth did not protect preterm fetal sheep from lung
      injury.
AB  - Sustained lung inflations (SI) at birth may recruit functional residual capacity
      (FRC). Clinically, SI increase oxygenation and decrease need for intubation in
      preterm infants. We tested whether a SI to recruit FRC would decrease lung injury
      from subsequent ventilation of fetal, preterm lambs. The preterm fetus (128+/-1
      day gestation) was exteriorized from the uterus, a tracheostomy was performed,
      and fetal lung fluid was removed. While maintaining placental circulation,
      fetuses were randomized to one of four 15-min interventions: 1) positive end
      expiratory pressure (PEEP) 8 cmH2O (n=4), 2) 20 s SI to 50 cmH2O then PEEP 8
      cmH2O (n=10), 3) mechanical ventilation at tidal volume (VT) 7 ml/kg (n=13), or
      4) 20 s SI then ventilation at VT 7 ml/kg (n=13). Lambs were ventilated with 95%
      N2/5% CO2 and PEEP 8 cmH2O. Volume recruitment was measured during SI, and fetal
      tissues were collected after an additional 30 min on placental support. SI
      achieved a mean FRC recruitment of 15 ml/kg (range 8-27). Fifty percent of final
      FRC was achieved by 2 s, 65% by 5 s, and 90% by 15 s, demonstrating prolonged SI
      times are needed to recruit FRC. SI alone released acute-phase proteins into the
      fetal lung fluid and increased mRNA expression of proinflammatory cytokines and
      acute-phase response genes in the lung. Mechanical ventilation further increased
      all markers of lung injury. SI before ventilation, regardless of the volume of
      FRC recruited, did not alter the acute-phase and proinflammatory responses to
      mechanical ventilation at birth.

PMID- 23873842
TI  - Quercetin acutely relaxes airway smooth muscle and potentiates beta-agonist
      induced relaxation via dual phosphodiesterase inhibition of PLCbeta and PDE4.
AB  - Asthma is a disease of the airways with symptoms including exaggerated airway
      narrowing and airway inflammation. Early asthma therapies used methylxanthines to
      relieve symptoms, in part, by inhibiting cyclic nucleotide phosphodiesterases
      (PDEs), the enzyme responsible for degrading cAMP. The classification of tissue
      specific PDE subtypes and the clinical introduction of PDE-selective inhibitors
      for chronic obstructive pulmonary disease (i.e., roflumilast) have reopened the
      possibility of using PDE inhibition in the treatment of asthma. Quercetin is a
      naturally derived PDE4-selective inhibitor found in fruits, vegetables, and tea.
      We hypothesized that quercetin relaxes airway smooth muscle via cAMP-mediated
      pathways and augments beta-agonist relaxation. Tracheal rings from male A/J mice
      were mounted in myographs and contracted with acetylcholine (ACh). Addition of
      quercetin (100 nM-1 mM) acutely and concentration-dependently relaxed airway
      rings precontracted with ACh. In separate studies, pretreatment with quercetin
      (100 MUM) prevented force generation upon exposure to ACh. In additional studies,
      quercetin (50 MUM) significantly potentiated isoproterenol-induced relaxations.
      In in vitro assays, quercetin directly attenuated phospholipase C activity,
      decreased inositol phosphate synthesis, and decreased intracellular calcium
      responses to Gq-coupled agonists (histamine or bradykinin). Finally, nebulization
      of quercetin (100 MUM) in an in vivo model of airway responsiveness significantly
      attenuated methacholine-induced increases in airway resistance. These novel data
      show that the natural PDE4-selective inhibitor quercetin may provide therapeutic
      relief of asthma symptoms and decrease reliance on short-acting beta-agonists. 

PMID- 23873845
TI  - Base-free production of H2 by dehydrogenation of formic acid using an iridium
      bisMETAMORPhos complex.
AB  - Erase the base: An iridium complex based on a cooperative ligand that functions
      as an internal base is reported. This complex can rapidly and cleanly
      dehydrogenate formic acid in absence of external base, a reaction that is
      required if formic acid is to be exploited as an energy carrier (see scheme).

PMID- 23873844
TI  - Reduced microtubule acetylation in cystic fibrosis epithelial cells.
AB  - Dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) leads to
      many cellular consequences, including perinuclear accumulation of free
      cholesterol due to impaired endosomal transport. The hypothesis being tested is
      that CF-related perinuclear cholesterol accumulation due to disrupted endocytic
      trafficking occurs as a result of reduced microtubule (MT) acetylation. Here, it
      is identified that acetylated-alpha-tubulin (Ac-tub) content is reduced by ~40%
      compared with respective wild-type controls in both cultured CF cell models (IB3)
      and primary Cftr-/- mouse nasal epithelial tissue. Histone deacetylase 6 (HDAC6)
      has been shown to regulate MT acetylation, which provides reasonable grounds to
      test its impact on reduced Ac-tub content on CF cellular phenotypes. Inhibition
      of HDAC6, either through tubastatin treatment or HDAC6 knockdown in CF cells,
      increases Ac-tub content and results in redistributed free cholesterol and
      reduced stimulation of NF-kappaB activity. Mechanistically, endoplasmic reticulum
      stress, which is widely reported in CF and leads to aggresome formation, is
      identified as a regulator of MT acetylation. F508del CFTR correction with C18 in
      primary airway epithelial cells restores MT acetylation and cholesterol
      transport. A significant role for phosphatidyl inositol-3 kinase p110alpha is
      also identified as a regulator of MT acetylation. 

PMID- 23873846
TI  - Polypropylene surgical mesh coated with extracellular matrix mitigates the host
      foreign body response.
AB  - Surgical mesh devices composed of synthetic materials are commonly used for
      ventral hernia repair. These materials provide robust mechanical strength and are
      quickly incorporated into host tissue; factors that contribute to reduced hernia
      recurrence rates. However, such mesh devices cause a foreign body response with
      the associated complications of fibrosis and patient discomfort. In contrast,
      surgical mesh devices composed of naturally occurring extracellular matrix (ECM)
      are associated with constructive tissue remodeling, but lack the mechanical
      strength of synthetic materials. A method for applying a porcine dermal ECM
      hydrogel coating to a polypropylene mesh is described herein with the associated
      effects upon the host tissue response and biaxial mechanical behavior. Uncoated
      and ECM coated heavy-weight BARDTM Mesh were compared to the light-weight
      ULTRAPROTM and BARDTM Soft Mesh devices in a rat partial thickness abdominal
      defect overlay model. The ECM coated mesh attenuated the pro-inflammatory
      response compared to all other devices, with a reduced cell accumulation and
      fewer foreign body giant cells. The ECM coating degraded by 35 days, and was
      replaced with loose connective tissue compared to the dense collagenous tissue
      associated with the uncoated polypropylene mesh device. Biaxial mechanical
      characterization showed that all of the mesh devices were of similar isotropic
      stiffness. Upon explanation, the light-weight mesh devices were more compliant
      than the coated or uncoated heavy-weight devices. This study shows that an ECM
      coating alters the default host response to a polypropylene mesh, but not the
      mechanical properties in an acute in vivo abdominal repair model.

PMID- 23873847
TI  - Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared
      with rituximab and ofatumumab in vitro and in xenograft models.
AB  - We report the first preclinical in vitro and in vivo comparison of GA101
      (obinutuzumab), a novel glycoengineered type II CD20 monoclonal antibody, with
      rituximab and ofatumumab, the two currently approved type I CD20 antibodies. The
      three antibodies were compared in assays measuring direct cell death (AnnexinV/PI
      staining and time-lapse microscopy), complement-dependent cytotoxicity (CDC),
      antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell
      mediated phagocytosis (ADCP), and internalization. The models used for the
      comparison of their activity in vivo were SU-DHL4 and RL xenografts. GA101 was
      found to be superior to rituximab and ofatumumab in the induction of direct cell
      death (independent of mechanical manipulation required for cell aggregate
      disruption formed by antibody treatment), whereas it was 10 to 1,000 times less
      potent in mediating CDC. GA101 showed superior activity to rituximab and
      ofatumumab in ADCC and whole-blood B-cell depletion assays, and was comparable
      with these two in ADCP. GA101 also showed slower internalization rate upon
      binding to CD20 than rituximab and ofatumumab. In vivo, GA101 induced a strong
      antitumor effect, including complete tumor remission in the SU-DHL4 model and
      overall superior efficacy compared with both rituximab and ofatumumab. When
      rituximab-pretreated animals were used, second-line treatment with GA101 was
      still able to control tumor progression, whereas tumors escaped rituximab
      treatment. Taken together, the preclinical data show that the glyoengineered type
      II CD20 antibody GA101 is differentiated from the two approved type I CD20
      antibodies rituximab and ofatumumab by its overall preclinical activity, further
      supporting its clinical investigation.

PMID- 23873848
TI  - The dual pathway inhibitor rigosertib is effective in direct patient tumor
      xenografts of head and neck squamous cell carcinomas.
AB  - The dual pathway inhibitor rigosertib inhibits phosphoinositide 3-kinase (PI3K)
      pathway activation as well as polo-like kinase 1 (PLK1) activity across a broad
      spectrum of cancer cell lines. The importance of PIK3CA alterations in squamous
      cell carcinoma of the head and neck (HNSCC) has raised interest in exploring
      agents targeting PI3K, the product of PIK3CA. The genetic and molecular basis of
      rigosertib treatment response was investigated in a panel of 16 HNSCC cell lines,
      and direct patient tumor xenografts from eight patients with HNSCC [four HPV
      serotype16 (HPV16)-positive]. HNSCC cell lines and xenografts were characterized
      by pathway enrichment gene expression analysis, exon sequencing, gene copy
      number, Western blotting, and immunohistochemistry (IHC). Rigosertib had potent
      antiproliferative effects on 11 of 16 HPV(-) HNSCC cell lines. Treatment
      sensitivity was confirmed in two cell lines using an orthotopic in vivo xenograft
      model. Growth reduction after rigosertib treatment was observed in three of eight
      HNSCC direct patient tumor lines. The responsive tumor lines carried a
      combination of a PI3KCA-activating event (amplification or mutation) and a p53
      inactivating event (either HPV16- or mutation-mediated TP53 inactivation). In
      this study, we evaluated the in vitro and in vivo efficacy of rigosertib in both
      HPV(+) and HPV(-) HNSCCs, focusing on inhibition of the PI3K pathway. Although
      consistent inhibition of the PI3K pathway was not evident in HNSCC, we identified
      a combination of PI3K/TP53 events necessary, but not sufficient, for rigosertib
      sensitivity.

PMID- 23873850
TI  - Combination drug scheduling defines a "window of opportunity" for
      chemopotentiation of gemcitabine by an orally bioavailable, selective ChK1
      inhibitor, GNE-900.
AB  - Checkpoint kinase 1 (ChK1) is a serine/threonine kinase that functions as a
      central mediator of the intra-S and G2-M cell-cycle checkpoints. Following DNA
      damage or replication stress, ChK1-mediated phosphorylation of downstream
      effectors delays cell-cycle progression so that the damaged genome can be
      repaired. As a therapeutic strategy, inhibition of ChK1 should potentiate the
      antitumor effect of chemotherapeutic agents by inactivating the postreplication
      checkpoint, causing premature entry into mitosis with damaged DNA resulting in
      mitotic catastrophe. Here, we describe the characterization of GNE-900, an ATP
      competitive, selective, and orally bioavailable ChK1 inhibitor. In combination
      with chemotherapeutic agents, GNE-900 sustains ATR/ATM signaling, enhances DNA
      damage, and induces apoptotic cell death. The kinetics of checkpoint abrogation
      seems to be more rapid in p53-mutant cells, resulting in premature mitotic entry
      and/or accelerated cell death. Importantly, we show that GNE-900 has little
      single-agent activity in the absence of chemotherapy and does not grossly
      potentiate the cytotoxicity of gemcitabine in normal bone marrow cells. In vivo
      scheduling studies show that optimal administration of the ChK1 inhibitor
      requires a defined lag between gemcitabine and GNE-900 administration. On the
      refined combination treatment schedule, gemcitabine's antitumor activity against
      chemotolerant xenografts is significantly enhanced and dose-dependent
      exacerbation of DNA damage correlates with extent of tumor growth inhibition. In
      summary, we show that in vivo potentiation of gemcitabine activity is mechanism
      based, with optimal efficacy observed when S-phase arrest and release is followed
      by checkpoint abrogation with a ChK1 inhibitor.

PMID- 23873849
TI  - Targeting aberrant DNA double-strand break repair in triple-negative breast
      cancer with alpha-particle emitter radiolabeled anti-EGFR antibody.
AB  - The higher potential efficacy of alpha-particle radiopharmaceutical therapy lies
      in the 3- to 8-fold greater relative biological effectiveness (RBE) of alpha
      particles relative to photon or beta-particle radiation. This greater RBE,
      however, also applies to normal tissue, thereby reducing the potential advantage
      of high RBE. As alpha particles typically cause DNA double-strand breaks (DSB),
      targeting tumors that are defective in DSB repair effectively increases the RBE,
      yielding a secondary, RBE-based differentiation between tumor and normal tissue
      that is complementary to conventional, receptor-mediated tumor targeting. In some
      triple-negative breast cancers (TNBC; ER(-)/PR(-)/HER-2(-)), germline mutation in
      BRCA-1, a key gene in homologous recombination DSB repair, predisposes patients
      to early onset of breast cancer. These patients have few treatment options once
      the cancer has metastasized. In this study, we investigated the efficacy of alpha
      particle emitter, (213)Bi-labeled anti-EGF receptor antibody, cetuximab, in BRCA
      1-defective TNBC. (213)Bi-cetuximab was found to be significantly more effective
      in the BRCA-1-mutated TNBC cell line HCC1937 than BRCA-1-competent TNBC cell MDA
      MB-231. siRNA knockdown of BRCA-1 or DNA-dependent protein kinase, catalytic
      subunit (DNA-PKcs), a key gene in non-homologous end-joining DSB repair pathway,
      also sensitized TNBC cells to (213)Bi-cetuximab. Furthermore, the small-molecule
      inhibitor of DNA-PKcs, NU7441, sensitized BRCA-1-competent TNBC cells to alpha
      particle radiation. Immunofluorescent staining of gamma-H2AX foci and comet assay
      confirmed that enhanced RBE is caused by impaired DSB repair. These data offer a
      novel strategy for enhancing conventional receptor-mediated targeting with an
      additional, potentially synergistic radiobiological targeting that could be
      applied to TNBC.

PMID- 23873852
TI  - Specific neurological phenotypes in autism spectrum disorders are associated with
      sex representation.
AB  - Autism spectrum disorder (ASD) is a heritable disorder occurring predominantly in
      males. The aim of this study was to compare sex differences in the prevalence of
      specific neurological phenotypes commonly described in ASD. The study included
      663 participants, aged 18 months to 15 years, diagnosed with ASD. Neurological
      and behavioral assessments were performed using standardized tests, and obtaining
      medical, developmental, and familial histories from the parents. Phenotypes under
      investigation were macro- and microcephaly, developmental regression, minor
      neurological and musculoskeletal deficits (MNMD), and seizures. Male : female
      ratio in the ASD group was 6.7:1. No sex differences in autism severity,
      cognitive ability, and adaptive functioning were noted. Mean head circumference
      percentile for males (50.1 +/- 25.6) was significantly larger than females (43.4
      +/- 30.2). Micro- and macrocephaly were more frequent in ASD than expected (5.9%;
      18.1%, respectively). Microcephaly in females (15.1%) was significantly more
      prevalent than in males (4.5%). The prevalence of macrocephaly in both sexes did
      not differ significantly. Regression was noted in 30.2% of the females with ASD,
      significantly higher than in males (18.9%). MNMD was documented in 73.8% of the
      females, significantly higher than in males (57.1%). M:F ratio decreased in a
      group with two or more phenotypes (3.6:1), while male predominance was more
      significant in the group without phenotypes (13.6:1). Neurological phenotypes
      associated with ASD are more prevalent in females than in males, resulting in
      more complex clinical and neurological manifestations in females. Therefore,
      involvement of different etiologies is suggested in ASD in females.

PMID- 23873851
TI  - Uracil-DNA glycosylase expression determines human lung cancer cell sensitivity
      to pemetrexed.
AB  - Uracil misincorporation into DNA is a consequence of pemetrexed inhibition of
      thymidylate synthase. The base excision repair (BER) enzyme uracil-DNA
      glycosylase (UNG) is the major glycosylase responsible for removal of
      misincorporated uracil. We previously illustrated hypersensitivity to pemetrexed
      in UNG(-/-) human colon cancer cells. Here, we examined the relationship between
      UNG expression and pemetrexed sensitivity in human lung cancer. We observed a
      spectrum of UNG expression in human lung cancer cells. Higher levels of UNG are
      associated with pemetrexed resistance and are present in cell lines derived from
      pemetrexed-resistant histologic subtypes (small cell and squamous cell
      carcinoma). Acute pemetrexed exposure induces UNG protein and mRNA, consistent
      with upregulation of uracil-DNA repair machinery. Chronic exposure of H1299
      adenocarcinoma cells to increasing pemetrexed concentrations established drug
      resistant sublines. Significant induction of UNG protein confirmed upregulation
      of BER as a feature of acquired pemetrexed resistance. Cotreatment with the BER
      inhibitor methoxyamine overrides pemetrexed resistance in chronically exposed
      cells, underscoring the use of BER-directed therapeutics to offset acquired drug
      resistance. Expression of UNG-directed siRNA and shRNA enhanced sensitivity in
      A549 and H1975 cells, and in drug-resistant sublines, confirming that UNG
      upregulation is protective. In human lung cancer, UNG deficiency is associated
      with pemetrexed-induced retention of uracil in DNA that destabilizes DNA
      replication forks resulting in DNA double-strand breaks and cell death. Thus, in
      experimental models, UNG is a critical mediator of pemetrexed sensitivity that
      warrants evaluation to determine clinical value.

PMID- 23873853
TI  - Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a
      high drinking risk level: results from a subgroup analysis of two randomized
      controlled 6-month studies.
AB  - AIMS: The aim of the study was to investigate the efficacy and safety of as
      needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in
      patients who did not reduce their alcohol consumption after an initial
      assessment, i.e. the pooled subgroup of patients with at least a high drinking
      risk level (men: >60 g/day; women: >40 g/day) at both screening and randomization
      from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and
      ESENSE 2 (NCT00812461). METHODS: Nalmefene 18 mg and placebo were taken on an as
      needed basis. All the patients also received a motivational and adherence
      enhancing intervention (BRENDA). The co-primary outcomes were number of heavy
      drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6
      measured using the Timeline Follow-back method. Additionally, data on clinical
      improvement, liver function and safety were collected throughout the study.
      RESULTS: The pooled population consisted of 667 patients: placebo n = 332;
      nalmefene n = 335. There was a superior effect of nalmefene compared with placebo
      in reducing the number of HDDs [treatment difference: -3.2 days (95% CI: -4.8; 
      1.6); P < 0.0001] and total alcohol consumption [treatment difference: -14.3
      g/day (-20.8; -7.8); P < 0.0001] at Month 6. Improvements in clinical status and
      liver parameters were greater in the nalmefene group compared with the placebo
      group. Adverse events and adverse events leading to dropout were more common with
      nalmefene than placebo. CONCLUSION: As-needed nalmefene was efficacious in
      reducing alcohol consumption in patients with at least a high drinking risk level
      at both screening and randomization, and the effect in this subgroup was larger
      than in the total population.

PMID- 23873854
TI  - Therapeutic potential of turmeric in Alzheimer's disease: curcumin or
      curcuminoids?
AB  - Alzheimer's disease (AD) is the most common form of dementia. There is limited
      choice in modern therapeutics, and drugs available have limited success with
      multiple side effects in addition to high cost. Hence, newer and alternate
      treatment options are being explored for effective and safer therapeutic targets
      to address AD. Turmeric possesses multiple medicinal uses including treatment for
      AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and
      bisdemethoxycurcumin, are vital constituents of turmeric. It is generally
      believed that curcumin is the most important constituent of the curcuminoid
      mixture that contributes to the pharmacological profile of parent curcuminoid
      mixture or turmeric. A careful literature study reveals that the other two
      constituents of the curcuminoid mixture also contribute significantly to the
      effectiveness of curcuminoids in AD. Therefore, it is emphasized in this review
      that each component of the curcuminoid mixture plays a distinct role in making
      curcuminoid mixture useful in AD, and hence, the curcuminoid mixture represents
      turmeric in its medicinal value better than curcumin alone. The progress in
      understanding the disease etiology demands a multiple-site-targeted therapy, and
      the curcuminoid mixture of all components, each with different merits, makes this
      mixture more promising in combating the challenging disease.

PMID- 23873855
TI  - Using a systems biology approach to understand and study the mechanisms of
      metastasis.
AB  - Metastasis remains the main cause for cancer-related deaths due to the lack of
      effective therapy. The clonal selection model has long been thought to be the
      primary mechanism of metastatic progression but many different mechanisms have
      been hypothesized for the progression from tumorigenesis to the successful
      dissemination and expansion of tumor cells at the secondary site. MicroRNAs,
      germline polymorphisms in combination with the tumor microenvironment are few of
      the different pathways to explain the metastatic cascade. Technological advances
      for high-throughput screening of cells such as expression profiling, next
      generation sequencing, as well as global network analyses have advanced the
      studies of these mechanisms. Combined with new insights into the various
      mechanisms of metastasis a systems biology approach has also been shown to be
      useful in identifying metastasis-specific gene signatures as well as predicting
      disease outcome. Furthermore, the results of these studies have been relevant for
      identifying biomarkers for metastatic disease.

PMID- 23873856
TI  - Inhibition of GluN2A-containing N-methyl-D-aspartate receptors by 2-naphthoic
      acid.
AB  - N-Methyl-D-aspartate (NMDA) receptors mediate excitatory synaptic transmission in
      the central nervous system and play important roles in synaptic development and
      plasticity, but also mediate glutamate neurotoxicity. Recently, 2-naphthoic acid
      (NPA) and its derivatives have been identified as allosteric, noncompetitive NMDA
      receptor inhibitors. The selectivity of NPA derivatives among NMDA receptor
      subtypes was mapped structurally to the ligand-binding domain, and was proposed
      to be mediated by residues on the S1 segment. To delineate the kinetic mechanism
      by which NPA inhibits NMDA receptor activity, we examined its effects on the NMDA
      receptor gating reaction. Using whole-cell patch clamping on human embryonic
      kidney 293 cells expressing recombinant NMDA family of glutamate receptor
      subunits, GluN1/GluN2A, we found that NPA has a 50% inhibitory effect at 1.9 mM.
      Further, from one-channel current recordings, we found that 4 mM NPA caused a 62%
      decrease in open probability by decreasing mean open time 2.5-fold and by
      increasing mean closed time 2-fold. Kinetic modeling suggested that NPA binding
      stabilized NMDA receptor closed states and increased the energy barriers toward
      open states, causing NMDA receptors to dwell longer in pre-open states along the
      activation pathway. The reaction mechanisms we derived provide quantitative
      insight into the inhibitory mechanism of NPA and help anticipate its effects on
      GluN1/GluN2A receptors during both physiologic and pathologic activation
      modalities.

PMID- 23873857
TI  - Complete percutaneous approach for arterial access in transfemoral transcatheter
      aortic valve replacement: a comparison with surgical cut-down and closure.
AB  - OBJECTIVES: This study sought to investigate the immediate safety and feasibility
      of complete percutaneous access/closure of arteriotomy for device deployment
      compared to the surgical approach for transfemoral transcatheter aortic valve
      replacement (TAVR). BACKGROUND: The percutaneous approach for arterial access for
      device deployment in transfemoral TAVR is a potential alternative to the surgical
      approach. METHODS: In 274 patients who underwent transfemoral TAVR using Edward
      Sapien heart valve, 140 had a complete percutaneous approach using a "pre
      closure" technique whereas 134 had surgical cut-down/repair for arterial
      access/closure of device deployment. Immediate vascular access/closure success,
      associated complications and clinical outcomes were compared. RESULTS: While
      overall acute success of access/closure and in-hospital access-related events
      were similar, significant isolated stenosis/dissection at the access site
      developed more frequently in the percutaneous group (7.1% vs. 0.7%, P = 0.007).
      Contrary, wound infections requiring prolonged antibiotics use or surgical
      debridement occurred more frequently in the surgical group (0.7% vs. 6.7%, P =
      0.007). Although the rate of major vascular complications was not different, the
      surgical group developed more frequent minor bleeding (27.1% vs. 38.8%, P = 0.04)
      and underwent transfusion of packed red blood cells of <=3 units (25.7% vs.
      43.3%, P = 0.002). Median hospital stay was shorter in the percutaneous group (3
      days vs. 4 days, P = 0.002). CONCLUSIONS: The percutaneous approach is a feasible
      access/closure method with a potential of lowering access site infection and
      bleeding, and shortening hospital stay, while maintaining similar rates of major
      vascular complications compared to the surgical approach.

PMID- 23873859
TI  - A carer's perspective: the view from Australia.

PMID- 23873858
TI  - Disrupted prefrontal interhemispheric structural coupling in schizophrenia
      related to working memory performance.
AB  - BACKGROUND: Prominent regional cortical thickness reductions have been shown in
      schizophrenia. In contrast, little is known regarding alterations of structural
      coupling between regions in schizophrenia and how these alterations may be
      related to cognitive impairments in this disorder. METHODS: T1-weighted magnetic
      resonance images were acquired in 54 patients with schizophrenia and 68 healthy
      control subjects aged 18-55 years. Cortical thickness was compared between groups
      using a vertex-wise approach. To assess structural coupling, seeds were selected
      within regions of reduced thickness, and brain-wide cortical thickness
      correlations were compared between groups. The relationships between identified
      patterns of circuit structure disruption and cognitive task performance were then
      explored. RESULTS: Prominent cortical thickness reductions were found in patients
      compared with controls at a 5% false discovery rate in a predominantly frontal
      and temporal pattern. Correlations of the left dorsolateral prefrontal cortex
      (DLPFC) with right prefrontal regions were significantly different in patients
      and controls. The difference remained significant in a subset of 20 first-episode
      patients. Participants with stronger frontal interhemispheric thickness
      correlations had poorer working memory performance. CONCLUSIONS: We identified
      structural impairment in a left-right DLPFC circuit in patients with
      schizophrenia independent of illness stage or medication exposure. The
      relationship between left-right DLPFC thickness correlations and working memory
      performance implicates prefrontal interhemispheric circuit impairment as a
      vulnerability pathway for poor working memory performance. Our findings could
      guide the development of novel therapeutic interventions aimed at improving
      working memory performance in patients with schizophrenia.

PMID- 23873860
TI  - Expanding analytical possibilities concerning the detection of stanozolol misuse
      by means of high resolution/high accuracy mass spectrometric detection of
      stanozolol glucuronides in human sports drug testing.
AB  - Anabolic-androgenic steroids (AAS) represent one of the most frequently detected
      classes of prohibited substances in doping controls. Due to their long-lasting
      beneficial effects on athletic performance, utmost retrospectivity via urine
      analysis is desirable and accomplished by targeting long-term metabolites of the
      respective drugs. In case of stanozolol, a substantial variety of metabolites has
      enabled the identification of numerous adverse analytical findings in the past,
      and recent studies concerning complementary phase-I and phase-II metabolites has
      further expanded the windows of opportunity for detecting the abuse of
      stanozolol. In this study, the utility of liquid chromatography-high
      resolution/high accuracy (tandem) mass spectrometry (LC-MS/MS) for the detection
      of 3'-OH-stanozolol glucuronide in sports drug testing is presented and the
      identification of two additional and so far unreported metabolites is shown. The
      structures of the complementary glucuronic acid conjugates were attributed to
      stanozolol-N-glucuronide and 17-epistanozolol-N-glucuronide. By means of chemical
      synthesis, stanozolol-N-glucuronide was prepared and used to corroborate the
      suggested structures. The 3'-OH-stanozolol glucuronide and the newly identified
      target compounds were implemented into routine sports drug test assays consisting
      of direct injection LC-MS/MS or solid-phase extraction (SPE) followed by LC
      MS/MS. A considerably expanded detection window for stanozolol abuse was
      demonstrated compared to the use of conventional phase-I metabolites and
      methodologies based on, for example, low resolution LC-MS/MS or gas
      chromatography-tandem mass spectrometry (GC-MS/MS). The commercial availability
      of 3'-OH-stanozolol glucuronide has been of great value for confirmatory
      purposes, and 17-epistanozolol-N-glucuronide was found to be a favourable long
      term metabolite for doping controls as it was observed up to 28 days post
      administration of the drug. Applying the established methodology over a period of
      six months to 659 routine sports drug testing samples, a total of 85 adverse
      analytical findings was uncovered, 72 of which would have remained undetected
      using earlier employed GC-MS/MS approaches.

PMID- 23873861
TI  - Physiological role of Acyl coenzyme A synthetase homologs in lipid metabolism in
      Neurospora crassa.
AB  - Acyl coenzyme A (CoA) synthetase (ACS) enzymes catalyze the activation of free
      fatty acids (FAs) to CoA esters by a two-step thioesterification reaction.
      Activated FAs participate in a variety of anabolic and catabolic lipid metabolic
      pathways, including de novo complex lipid biosynthesis, FA beta-oxidation, and
      lipid membrane remodeling. Analysis of the genome sequence of the filamentous
      fungus Neurospora crassa identified seven putative fatty ACSs (ACS-1 through ACS
      7). ACS-3 was found to be the major activator for exogenous FAs for anabolic
      lipid metabolic pathways, and consistent with this finding, ACS-3 localized to
      the endoplasmic reticulum, plasma membrane, and septa. Double-mutant analyses
      confirmed partial functional redundancy of ACS-2 and ACS-3. ACS-5 was determined
      to function in siderophore biosynthesis, indicating alternative functions for ACS
      enzymes in addition to fatty acid metabolism. The N. crassa ACSs involved in
      activation of FAs for catabolism were not specifically defined, presumably due to
      functional redundancy of several of ACSs for catabolism of exogenous FAs. 

PMID- 23873862
TI  - Synchronous activation of cell division by light or temperature stimuli in the
      dimorphic yeast Schizosaccharomyces japonicus.
AB  - Many fungi respond to light and regulate fungal development and behavior. A blue
      light-activated complex has been identified in Neurospora crassa as the product
      of the wc-1 and wc-2 genes. Orthologs of WC-1 and WC-2 have hitherto been found
      only in filamentous fungi and not in yeast, with the exception of the
      basidiomycete pathogenic yeast Cryptococcus. Here, we report that the fission
      yeast Schizosaccharomyces japonicus responds to blue light depending on Wcs1 and
      Wcs2, orthologs of components of the WC complex. Surprisingly, those of
      ascomycete S. japonicus are more closely related to those of the basidiomycete.
      S. japonicus reversibly changes from yeast to hyphae in response to environmental
      stresses. After incubation at 30 degrees C, a colony of yeast was formed, and
      then hyphal cells extended from the periphery of the colony. When light cycles
      were applied, distinct dark- and bright-colored hyphal cell stripes were formed
      because the growing hyphal cells had synchronously activated cytokinesis. In
      addition, temperature cycles of 30 degrees C for 12 h and 35 degrees C for 12 h
      or of 25 degrees C for 12 h and 30 degrees C for 12 h during incubation in the
      dark induced a response in the hyphal cells similar to that of light. The stripe
      formation of the temperature cycles was independent of the wcs genes. Both light
      and temperature, which are daily external cues, have the same effect on growing
      hyphal cells. A dual sensing mechanism of external cues allows organisms to adapt
      to daily changes of environmental alteration. 

PMID- 23873863
TI  - Novel thioredoxin-like proteins are components of a protein complex coating the
      cortical microtubules of Toxoplasma gondii.
AB  - Microtubules are versatile biopolymers that support numerous vital cellular
      functions in eukaryotes. The specific properties of microtubules are dependent on
      distinct microtubule-associated proteins, as the tubulin subunits and microtubule
      structure are exceptionally conserved. Highly specialized microtubule-containing
      assemblies are often found in protists, which are rich sources for novel
      microtubule-associated proteins. A protozoan parasite, Toxoplasma gondii,
      possesses several distinct tubulin-containing structures, including 22
      microtubules closely associated with the cortical membrane. Early ultrastructural
      studies have shown that the cortical microtubules are heavily decorated with
      associating proteins. However, little is known about the identities of these
      proteins. Here, we report the discovery of a novel protein, TrxL1 (for
      Thioredoxin-Like protein 1), and an associating complex that coats the cortical
      microtubules. TrxL1 contains a thioredoxin-like fold. To visualize its
      localization in live parasites by fluorescence, we replaced the endogenous TrxL1
      gene with an mEmeraldFP-TrxL1 fusion gene. Structured illumination-based
      superresolution imaging of this parasite line produced a detailed view of the
      microtubule cytoskeleton. Despite its stable association with the cortical
      microtubules in the parasite, TrxL1 does not seem to bind to microtubules
      directly. Coimmunoprecipitation experiments showed that TrxL1 associates with a
      protein complex containing SPM1, a previously reported microtubule-associated
      protein in T. gondii. We also found that SPM1 recruits TrxL1 to the cortical
      microtubules. Besides SPM1, several other novel proteins are found in the TrxL1
      containing complex, including TrxL2, a close homolog of TrxL1. Thus, our results
      reveal for the first time a microtubule-associated complex in T. gondii. 

PMID- 23873864
TI  - Protein kinase CK2 holoenzyme promotes start-specific transcription in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the entrance into S phase requires the activation of
      a specific burst of transcription, which depends on SBF (SCB binding factor,
      Swi4/Swi6) and MBF (MCB binding factor, Mbp1/Swi6) complexes. CK2 is a
      pleiotropic kinase involved in several cellular processes, including the
      regulation of the cell cycle. CK2 is composed of two catalytic subunits (alpha
      and alpha') and two regulatory subunits (beta and beta'), both of which are
      required to form the active holoenzyme. Here we investigate the function of the
      CK2 holoenzyme in Start-specific transcription. The ckb1Delta ckb2Delta mutant
      strain, bearing deletions of both genes encoding CK2 regulatory subunits, shows a
      delay of S-phase entrance due to a severe reduction of the expression of SBF- and
      MBF-dependent genes. This transcriptional defect is caused by an impaired
      recruitment of Swi6 and Swi4 to G1 gene promoters. Moreover, CK2 alpha and beta'
      subunits interact with RNA polymerase II, whose binding to G1 promoters is
      positively regulated by the CK2 holoenzyme. Collectively, these findings suggest
      a novel role for the CK2 holoenzyme in the activation of G1 transcription. 

PMID- 23873865
TI  - Independent localization of plasma membrane and chloroplast components during
      eyespot assembly.
AB  - Like many algae, Chlamydomonas reinhardtii is phototactic, using two anterior
      flagella to swim toward light optimal for photosynthesis. The flagella are
      responsive to signals initiated at the photosensory eyespot, which comprises
      photoreceptors in the plasma membrane and layers of pigment granules in the
      chloroplast. Phototaxis depends on placement of the eyespot at a specific
      asymmetric location relative to the flagella, basal bodies, and bundles of two or
      four highly acetylated microtubules, termed rootlets, which extend from the basal
      bodies toward the posterior of the cell. Previous work has shown that the eyespot
      is disassembled prior to cell division, and new eyespots are assembled in
      daughter cells adjacent to the nascent four-membered rootlet associated with the
      daughter basal body (D4), but the chronology of these assembly events has not
      been determined. Here we use immunofluorescence microscopy to follow assembly and
      acetylation of the D4 rootlet, localization of individual eyespot components in
      the plasma membrane or chloroplast envelope, and flagellar emergence during and
      immediately following cell division. We find that the D4 rootlet is assembled
      before the initiation of eyespot assembly, which occurs within the same time
      frame as rootlet acetylation and flagellar outgrowth. Photoreceptors in the
      plasma membrane are correctly localized in eyespot mutant cells lacking pigment
      granule layers, and chloroplast components of the eyespot assemble in mutant
      cells in which photoreceptor localization is retarded. The data suggest that
      plasma membrane and chloroplast components of the eyespot are independently
      responsive to a cytoskeletal positioning cue. 

PMID- 23873866
TI  - Differential regulation of white-opaque switching by individual subunits of
      Candida albicans mediator.
AB  - The multisubunit eukaryotic Mediator complex integrates diverse positive and
      negative gene regulatory signals and transmits them to the core transcription
      machinery. Mutations in individual subunits within the complex can lead to
      decreased or increased transcription of certain subsets of genes, which are
      highly specific to the mutated subunit. Recent studies suggest a role for
      Mediator in epigenetic silencing. Using white-opaque morphological switching in
      Candida albicans as a model, we have shown that Mediator is required for the
      stability of both the epigenetic silenced (white) and active (opaque) states of
      the bistable transcription circuit driven by the master regulator Wor1.
      Individual deletions of eight C. albicans Mediator subunits have shown that
      different Mediator subunits have dramatically diverse effects on the
      directionality, frequency, and environmental induction of epigenetic switching.
      Among the Mediator deletion mutants analyzed, only Med12 has a steady-state
      transcriptional effect on the components of the Wor1 circuit that clearly
      corresponds to its effect on switching. The MED16 and MED9 genes have been found
      to be among a small subset of genes that are required for the stability of both
      the white and opaque states. Deletion of the Med3 subunit completely destabilizes
      the opaque state, even though the Wor1 transcription circuit is intact and can be
      driven by ectopic expression of Wor1. The highly impaired ability of the med3
      deletion mutant to mate, even when Wor1 expression is ectopically induced,
      reveals that the activation of the Wor1 circuit can be decoupled from the opaque
      state and one of its primary biological consequences. 

PMID- 23873868
TI  - Numerical quadrature and operator splitting in finite element methods for cardiac
      electrophysiology.
AB  - We study the numerical accuracy and computational efficiency of alternative
      formulations of the finite element solution procedure for the monodomain
      equations of cardiac electrophysiology, focusing on the interaction of spatial
      quadrature implementations with operator splitting and examining both nodal and
      Gauss quadrature methods and implementations that mix nodal storage of state
      variables with Gauss quadrature. We evaluate the performance of all possible
      combinations of 'lumped' approximations of consistent capacitance and mass
      matrices. Most generally, we find that quadrature schemes and lumped
      approximations that produce decoupled nodal ionic equations allow for the
      greatest computational efficiency, this being afforded through the use of
      asynchronous adaptive time-stepping of the ionic state variable ODEs. We identify
      two lumped approximation schemes that exhibit superior accuracy, rivaling that of
      the most expensive variationally consistent implementations. Finally, we
      illustrate some of the physiological consequences of discretization error in
      electrophysiological simulation relevant to cardiac arrhythmia and fibrillation.
      These results suggest caution with the use of semi-automated free-form
      tetrahedral and hexahedral meshing algorithms available in most commercially
      available meshing software, which produce nonuniform meshes having a large
      distribution of element sizes.

PMID- 23873867
TI  - Candida albicans Czf1 and Efg1 coordinate the response to farnesol during quorum
      sensing, white-opaque thermal dimorphism, and cell death.
AB  - Quorum sensing by farnesol in Candida albicans inhibits filamentation and may be
      directly related to its ability to cause both mucosal and systemic diseases. The
      Ras1-cyclic AMP signaling pathway is a target for farnesol inhibition. However, a
      clear understanding of the downstream effectors of the morphological farnesol
      response has yet to be unraveled. To address this issue, we screened a library
      for mutants that fail to respond to farnesol. Six mutants were identified, and
      the czf1Delta/czf1Delta mutant was selected for further characterization. Czf1 is
      a transcription factor that regulates filamentation in embedded agar and also
      white-to-opaque switching. We found that Czf1 is required for filament inhibition
      by farnesol under at least three distinct environmental conditions: on agar
      surfaces, in liquid medium, and when embedded in a semisolid agar matrix. Since
      Efg1 is a transcription factor of the Ras1-cyclic AMP signaling pathway that
      interacts with and regulates Czf1, an efg1Delta/efg1Delta czf1Delta/czf1Delta
      mutant was tested for filament inhibition by farnesol. It exhibited an opaque
      cell-like temperature-dependent morphology, and it was killed by low farnesol
      levels that are sublethal to wild-type cells and both efg1Delta/efg1Delta and
      czf1Delta/czf1Delta single mutants. These results highlight a new role for Czf1
      as a downstream effector of the morphological response to farnesol, and along
      with Efg1, Czf1 is involved in the control of farnesol-mediated cell death in C.
      albicans. 

PMID- 23873869
TI  - A case of Toriello-Carey syndrome with severe congenital tracheal stenosis.
AB  - Toriello-Carey syndrome is rare condition characterized by agenesis of the corpus
      callosum, the Pierre Robin sequence, and facial anomalies such as telecanthus,
      short palpebral fissures, and a small nose with anteverted nares [Toriello and
      Carey, 1988]. In addition, tracheal and laryngeal anomalies are common
      complications in patients with Toriello-Carey syndrome, and these anomalies can
      lead to death [Kataoka et al., 2003]. Congenital tracheal stenosis is a life
      threatening condition with high mortality. Even if surgery is successful, several
      serious complications can result in a high risk of mortality. We describe a case
      of a Japanese boy with Toriello-Carey syndrome who had severe congenital tracheal
      stenosis, in whom surgical tracheal plasty was avoided because of adequate
      respiratory care, allowing the patient to be alive at 18 months of age.

PMID- 23873870
TI  - Migrant density and well-being--a national school survey of 15-year-olds in
      Sweden.
AB  - BACKGROUND: The aim of this study was to investigate the impact of migrant
      density in school on the well-being of pupils with a migrant origin in first as
      well as second generation. METHODS: Cross-sectional analysis of data from a
      national classroom survey of 15-year-old Swedish schoolchildren. The study
      population included 76 229 pupils (86.5% participation) with complete data set
      from 1352 schools. Six dimensions of well-being from the KIDSCREEN were analysed
      in two-level linear regression models to assess the influence of migrant origin
      at individual level and percentage of students with a migrant origin at school
      level, as well as interaction terms between them. Z-scores were used to equalize
      scales. RESULTS: A high density (>50%) of pupils with a migrant origin in first
      or second generation was associated with positive well-being on all six scales
      for foreign-born pupils originating in Africa or Asia compared with schools with
      low (<10%) migrant density. The effect sizes were 0.56 for boys and 0.29 for
      girls on the comprehensive KIDSCREEN 10-index (P<0.001) and 0.61 and 0.34,
      respectively, for psychological well-being (P<0.001). Of the boys and girls born
      in Africa or Asia, 31.6% and 34.6%, respectively, reported being bullied during
      the past week in schools with low (<10%) migrant density. CONCLUSIONS: Pupils
      born in Africa or Asia are at high risk for being bullied and having impaired
      well-being in schools with few other migrant children. School interventions to
      improve peer relations and prevent bullying are needed to promote well-being in
      non-European migrant children.

PMID- 23873871
TI  - A diagnostic conundrum: heterophilic antibody interference in an
      adrenocorticotropic hormone immunoassay not detectable using a proprietary
      heterophile blocking reagent.
AB  - CONTEXT: Heterophilic antibodies are a well-described interferent but poorly
      appreciated and are often not a recognized problem affecting most immunoassays.
      We describe for the first time heterophilic antibodies interference affecting an
      adrenocorticotropic hormone (ACTH) assay in a patient with Cushing's syndrome due
      to bilateral nodular adrenal hyperplasia. CASE: A 60-year-old retired female
      nurse underwent extensive invasive investigations, which were ultimately
      unnecessary, as a result of initial analytical interference in the ACTH assay,
      which could not be resolved using a proprietary heterophilic binding reagent.
      RESULTS: This case highlights the inherent difficulty of diagnosing Cushing's
      syndrome and the large emphasis placed on laboratory tests. The consequence of
      not initially identifying interference in this patient's laboratory test results
      led to unnecessary and costly investigations with potentially adverse outcomes.
      CONCLUSIONS: Clinicians and the laboratory community need to be continuously
      vigilant and view laboratory results with caution when they are inconsistent with
      the clinical picture. This approach is paramount, especially at a time of
      increasing automation and ever-diminishing scientist involvement in sample
      processing.

PMID- 23873872
TI  - Longitudinal assessment of thyroid function in pregnancy.
AB  - BACKGROUND: Trimester-specific reference intervals (RIs) for thyroid function
      tests are lacking for Beckman Dxl 800 analysers. We aimed to establish RIs for
      thyroid stimulating hormone (TSH), free thyroxine (fT4) and to track
      intraindividual changes in thyroid function throughout pregnancy. METHODS: One
      hundred and thirty healthy women without antithyroid peroxidase antibodies were
      followed longitudinally. Thyroid function was determined at trimester-1 (T1): 9
      13 weeks; trimester-2 (T2): 22-26 weeks; trimester-3 (T3): 35-39 weeks and
      postpartum (PP): 8-12 weeks. A subgroup (n = 47) was used to track
      intraindividual changes using PP as non-pregnant state (baseline). RESULTS: For
      trimesters 1-3, TSH (median (2.5th, 5th, 95th and 97.5th percentile)) was 0.77
      (0.03, 0.05, 2.33, 3.05), 1.17 (0.42, 0.47, 2.71, 3.36) and 1.35 (0.34, 0.42,
      2.65, 2.83) mIU/L, respectively. Free T4 (mean (95%CI)) was 10.7 (5.9-15.5), 8.1
      (4.9-11.3), 7.8 (4.5-11.0) pmol/L, respectively. In T2 and T3, 36% and 41% of the
      fT4 values, respectively, fell below the non-pregnancy lower normal limit. In the
      subgroup assessed for longitudinal changes, of the women with baseline TSH <=
      median, 71-75% remained at or below the corresponding median for trimesters 1-3.
      Of the women with baseline fT4 <= median, 69-81% also remained at or below the
      corresponding median for trimesters 1-3. High correlation was observed at
      different trimesters and baseline for TSH (Spearman's r: 0.593-0.846, P < 0.001)
      and for fT4 (r: 0.480-0.739, P < 0.001). CONCLUSIONS: Use of trimester-specific
      RIs would prevent misclassification of thyroid function during pregnancy. In the
      majority of women, TSH and fT4 tracked on the same side of the median
      distribution, from a non-pregnant baseline, throughout pregnancy.

PMID- 23873873
TI  - Levodopa therapy in Parkinson's disease: influence on liquid chromatographic
      tandem mass spectrometric-based measurements of plasma and urinary
      normetanephrine, metanephrine and methoxytyramine.
AB  - BACKGROUND: Medication-related interferences with measurements of catecholamines
      and their metabolites represent important causes of false-positive results during
      diagnosis of phaeochromocytomas and paragangliomas (PPGLs). Such interferences
      are less troublesome with measurements by liquid chromatography with tandem mass
      spectrometry (LC-MS/MS) than by other methods, but can still present problems for
      some drugs. Levodopa, the precursor for dopamine used in the treatment of
      Parkinson's disease, represents one potentially interfering medication. METHODS:
      Plasma and urine samples, obtained from 20 Parkinsonian patients receiving
      levodopa, were analysed for concentrations of catecholamines and their O
      methylated metabolites by LC-MS/MS. Results were compared with those from a group
      of 120 age-matched subjects and 18 patients with PPGLs. RESULTS: Plasma and
      urinary free and deconjugated (free + conjugated) methoxytyramine, as well as
      urinary dopamine, showed 22- to 148-fold higher (P < 0.0001) concentrations in
      patients receiving levodopa than in the reference group. In contrast, plasma
      normetanephrine, urinary noradrenaline and urinary free and deconjugated
      normetanephrine concentrations were unaffected. Plasma free metanephrine, urinary
      adrenaline and urinary free and deconjugated metanephrine all showed higher (P <
      0.05) concentrations in Parkinsonian patients than the reference group, but this
      was only a problem for adrenaline. Similar to normetanephrine, plasma and urinary
      metanephrine remained below the 97.5 percentiles of the reference group in almost
      all Parkinsonian patients. CONCLUSIONS: These data establish that although
      levodopa treatment confounds identification of PPGLs that produce dopamine, the
      therapy is not a problem for use of LC-MS/MS measurements of plasma and urinary
      normetanephrine and metanephrine to diagnose more commonly encountered PPGLs that
      produce noradrenaline or adrenaline.

PMID- 23873874
TI  - Tissue factor expression in neutrophil extracellular traps and neutrophil derived
      microparticles in antineutrophil cytoplasmic antibody associated vasculitis may
      promote thromboinflammation and the thrombophilic state associated with the
      disease.
AB  - OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis
      (AAV) is characterised by neutrophil activation. An elevated prevalence of venous
      thromboembolic events has been reported in AAV. Because of the critical role of
      neutrophils in inflammation associated thrombosis, we asked whether neutrophil
      tissue factor (TF) may be implicated in the thrombotic diathesis in AAV. METHODS:
      Neutrophils from four patients and sera from 17 patients with ANCA associated
      vasculitis with active disease and remission were studied. TF expression was
      assessed by immunoblotting and confocal microscopy. Circulating DNA levels were
      evaluated. TF expressing microparticles (MPs) were measured by flow cytometry and
      thrombin-antithrombin complex levels by ELISA. RESULTS: Peripheral blood
      neutrophils from four patients with active disease expressed elevated TF levels
      and released TF expressing neutrophil extracellular traps (NETs) and MPs. TF
      positive NETs were released by neutrophils isolated from the bronchoalveolar
      lavage and were detected in nasal and renal biopsy specimens. Elevated levels of
      circulating DNA and TF expressing neutrophil derived MPs were further observed in
      sera from patients with active disease. Induction of remission attenuated the
      aforementioned effects. Control neutrophils treated with sera from patients with
      active disease released TF bearing NETs and MPs which were abolished after IgG
      depletion. Treatment of control neutrophils with isolated IgG from sera from
      patients with active disease also resulted in the release of TF bearing NETs. TF
      implication in MP dependent thrombin generation was demonstrated by antibody
      neutralisation studies. CONCLUSIONS: Expression of TF in NETs and neutrophil
      derived MPs proposes a novel mechanism for the induction of thrombosis and
      inflammation in active AAV.

PMID- 23873875
TI  - Evaluation of myocardial function in patients with rheumatoid arthritis using
      strain imaging by speckle-tracking echocardiography.
AB  - OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk for
      cardiovascular disease (CVD), although strategies to detect subclinical CVD are
      poorly characterised. The purpose of this study was to assess myocardial function
      by speckle-tracking echocardiography strain imaging in patients with RA without
      known CVD. METHODS: Eighty-seven patients with RA selected from a population
      based sample underwent echocardiography. Left ventricular (LV) and right
      ventricular (RV) longitudinal peak systolic strain were measured. A subset of 59
      patients with RA was compared with 59 age-, gender- and race-matched subjects
      with normal echocardiography and no CVD or risk factors. RESULTS: The mean +/- SD
      age of the patients with RA and the normal patients was 55.7+/-12.1 and 54.5+/
      12.2 years (p=0.42), respectively, with 45 (76%) women in each group. Global LV
      strain (-15.7+/-3.2% vs -18.1+/-2.4%, p<0.001) and RV strain (-17.9+/-4.7% vs 
      20.7+/-2.4%, p<0.001) was reduced in patients with RA compared with normal
      patients. Among all 87 patients with RA the mean disease duration and C-reactive
      protein at echocardiography were 10.0+/-6.1 years and 3.5+/-3.7 mg/L, and 74%
      were seropositive. Adjusted univariate regression analysis demonstrated a
      significant correlation between global LV strain and RA Health Assessment
      Questionnaire disability index (p=0.032), and borderline associations with prior
      use of oral corticosteroids (p=0.062) and methotrexate (p=0.054) after adjustment
      for age, gender, blood pressure, body mass index, heart rate and LV mass index.
      CONCLUSIONS: Global longitudinal LV and RV strain is reduced in patients with RA
      compared with healthy patients. Strain abnormalities correlate with RA disease
      severity. Strain imaging by echocardiography may detect early myocardial
      dysfunction in RA.

PMID- 23873876
TI  - EULAR evidence-based and consensus-based recommendations on the management of
      medium to high-dose glucocorticoid therapy in rheumatic diseases.
AB  - To develop recommendations for the management of medium to high-dose (ie, >7.5 mg
      but <=100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in
      rheumatic diseases. A multidisciplinary EULAR task force was formed, including
      rheumatic patients. After discussing the results of a general initial search on
      risks of GC therapy, each participant contributed 10 propositions on key clinical
      topics concerning the safe use of medium to high-dose GCs. The final
      recommendations were selected via a Delphi consensus approach. A systematic
      literature search of PubMed, EMBASE and Cochrane Library was used to identify
      evidence concerning each of the propositions. The strength of recommendation was
      given according to research evidence, clinical expertise and patient preference.
      The 10 propositions regarded patient education and informing general
      practitioners, preventive measures for osteoporosis, optimal GC starting dosages,
      risk-benefit ratio of GC treatment, GC sparing therapy, screening for
      comorbidity, and monitoring for adverse effects. In general, evidence supporting
      the recommendations proved to be surprisingly weak. One of the recommendations
      was rejected, because of conflicting literature data. Nine final recommendations
      for the management of medium to high-dose systemic GC therapy in rheumatic
      diseases were selected and evaluated with their strengths of recommendations.
      Robust evidence was often lacking; a research agenda was created. 

PMID- 23873877
TI  - Anticarbamylated protein (anti-CarP) antibodies are present in sera of juvenile
      idiopathic arthritis (JIA) patients.

PMID- 23873878
TI  - Response to 'In erosive hand osteoarthritis more inflammatory signs on ultrasound
      are found than in the rest of hand osteoarthritis' by Kortekaas et al.

PMID- 23873880
TI  - Association of changes in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC)
      with changes in cartilage thickness in the medial tibiofemoral compartment of the
      knee: a 2 year follow-up study using 3.0 T MRI.
AB  - OBJECTIVE: To determine the association between changes in the delayed gadolinium
      enhanced MRI of cartilage (dGEMRIC) index over 2 years as a measure of cartilage
      proteoglycan concentration, with changes in cartilage thickness in the medial
      tibiofemoral compartment of knees in middle-aged women. METHODS: One hundred and
      forty-eight women (one knee for each subject) aged >=40 years were included. 3.0
      T MR images of the knee were acquired at baseline, 1 year and 2 years. Three
      dimensional (3D) spoiled gradient recalled echo (SPGR) sequences (for cartilage
      thickness) and 3D inversion recovery-prepared SPGR sequences after dGEMRIC were
      acquired. Segmentation was performed in the medial central (weight-bearing) femur
      and tibia to determine cartilage proteoglycan concentration and thickness. The
      association of change in the dGEMRIC indices between baseline and 1-year follow
      up with (a) concomitant changes in cartilage thickness and (b) change in
      cartilage thickness between 1 and 2 years was assessed using linear regression.
      RESULTS: In the whole-sample model, a decrease in dGEMRIC indices over time at
      the central medial femur significantly predicted an increase in cartilage
      thickness at both the central medial femur (p=0.008) and the medial tibia
      (p=0.04). CONCLUSIONS: A decrease in dGEMRIC indices was associated with an
      increase in cartilage thickness in the medial compartment. Our results suggest
      that an increase in cartilage thickness may also be related to a decrease in
      proteoglycan concentration, which may represent swelling of cartilage in early
      stages of degeneration.

PMID- 23873879
TI  - Global chemokine expression in systemic sclerosis (SSc): CCL19 expression
      correlates with vascular inflammation in SSc skin.
AB  - OBJECTIVE: To characterise global chemokine expression in systemic sclerosis
      (SSc) skin in order to better understand the relationship between chemokine
      expression and vascular inflammation in this disease. METHODS: We investigated
      chemokine mRNA expression in the skin through quantitative PCR analysis comparing
      patients with diffuse cutaneous (dcSSc) or limited cutaneous (lcSSc) disease with
      healthy controls. We tested correlations between the most regulated chemokines
      and vascular inflammation and macrophage recruitment. CCL19 expression was
      examined in human primary immune cells treated with innate immune activators.
      RESULTS: The chemokines, CCL18, CCL19 and CXCL13, were upregulated in dcSSc skin,
      and CCL18 in lcSSc skin. Expression of CCL19 in dcSSc skin correlated with
      markers of vascular inflammation and macrophage recruitment. Immunofluorescence
      data showed CCL19 colocalisation with CD163 macrophages in dcSSc skin. In vitro
      studies on human primary cells demonstrated that CCL19 expression was induced
      after toll-like receptor activation of peripheral blood mononuclear cells and
      separated populations of CD14 monocytes. CONCLUSIONS: CCL18, CCL19 and CXCL13
      chemoattractants for macrophage and T cell recruitment-were three of six
      chemokines with the highest expression in dcSSc skin. Increased CCL19 expression
      in the skin suggests a role for CCL19 in the recruitment of immune cells to the
      peripheral tissue. Induction of CCL19 in macrophages but not structural cells
      indicates a role for skin-resident or recruited immune cells in perivascular
      inflammation. This study demonstrates that CCL19 is a sensitive marker for the
      perivascular inflammation and immune cell recruitment seen in dcSSc skin disease.

PMID- 23873881
TI  - Prospective long term follow-up of a cohort of patients with giant cell arteritis
      screened for aortic structural damage (aneurysm or dilatation).
AB  - BACKGROUND: Aortic structural damage (ASD) may complicate the course of patients
      with giant cell arteritis (GCA). However the frequency and outcome of ASD has not
      been assessed in long term prospective studies. METHODS: In a previous screening
      of 54 biopsy proven GCA patients, significant ASD was detected in 12 (22.2%)
      after a median follow-up of 5.4 years. These patients were periodically evaluated
      (every 4 years) over a median of 10.3 years (range 4-16.6 years) in order to
      investigate the development of new ASD and the outcome of previously detected
      abnormalities. RESULTS: 18 of the 54 patients abandoned the study due to death or
      other reasons. The remaining 36 patients were subjected to a second screening and
      14 to a third screening. 12 (33.3%) of the 36 patients re-screened and 16 (29.6%)
      of the initial cohort developed ASD, all but one in the thoracic aorta. Aortic
      diameters at the ascending and descending aorta significantly increased over
      time. One patient (1.9% of the initial cohort) died from aortic dissection.
      Surgery was advised in eight (50%) patients with ASD but could only be performed
      in three patients (37.7%). The development of ASD was not associated with
      persistence of detectable disease activity. CONCLUSIONS: The incidence of ASD is
      maximal within the first 5 years after diagnosis but continues developing over
      time, affecting up to 33.3% of individuals after long term follow-up. Once ASD
      occurs, dilatation increases over time, underlining the need for periodic
      evaluation. Surgical repair is feasible in about one-third of candidates.

PMID- 23873882
TI  - An unusual case of traumatic wrist swelling.

PMID- 23873883
TI  - A review of causes of Stevens-Johnson syndrome and toxic epidermal necrolysis in
      children.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life
      threatening conditions almost exclusively attributed to drugs. The incidence in
      children is lower than in adults and has a better outcome. Mycosplama pneumoniae
      infection may be involved in some cases of paediatric SJS. The main etiologic
      factors for both SSJ and TEN are sulphonamides and anticonvulsants, followed by
      penicillins and non-steroidal anti-inflammatory drugs. In rare instances,
      paracetamol is the only suspected drug. By contrast with adults, allopurinol,
      oxicams and nevirapine are not identified as causative agents in children,
      probably due to differences in drug prescriptions. The only aspects of treatment
      that have been proved to improve survival are the rapid withdrawal of the
      suspected offending drugs and an optimal supportive therapy with emphasis in
      nutritional support, accompanied by management of denuded skin areas. The use of
      specific therapies remains controversial. 

PMID- 23873884
TI  - Advances in pediatric oncology MRI.
AB  - Refined stratification of disease is thought to result in better survival from
      childhood malignant disease while minimizing the adverse effects of anticancer
      therapies. There is a potential for magnetic resonance imaging (MRI) to
      contribute to such stratification by improved tissue characterization, anatomical
      depiction, staging, and assessment of early treatment response. Recent advances
      in pediatric MRI outside the central nervous system (CNS) are reviewed in this
      context. The focus is on new applications for conventional MRI and on clinical
      implementation of tissue-specific and quantitative techniques. This area is
      largely unexplored, and potential directions for research are indicated. 

PMID- 23873885
TI  - Imaging in juvenile idiopathic arthritis (JIA): an update with particular
      emphasis on MRI.
AB  - Juvenile idiopathic arthritis (JIA) is a heterogeneous condition encompassing all
      forms of chronic arthritis of unknown origin and with onset before 16 years of
      age. During the last decade new, potent therapeutic agents have become available,
      underscoring the need for accurate monitoring of therapeutic response on both
      disease activity and structural damage to the joint. However, so far, treatment
      efficacy is based on clinical ground only, although clinical parameters are poor
      markers for disease activity and progression of structural damage. Not so for
      rheumatoid arthritis patients where the inclusion of radiographic assessment has
      been required by FDA to test the disease-modifying potential of new anti
      rheumatic drugs. In imaging of children with JIA there has been a shift from
      traditional radiography towards newer techniques such as ultrasound and MRI,
      however without proper evaluation of their accuracy and validity. We here
      summarize present knowledge and discuss future challenges in imaging children
      with JIA. 

PMID- 23873886
TI  - Radial MRI during free breathing in contrast-enhanced hepatobiliary phase
      imaging.
AB  - BACKGROUND: Use of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid
      (Gd-EOB-DTPA) for diagnosis of hepatic tumors has been previously reported. Fat
      saturated 3D T1-weighted gradient echo sequence (TIGRE) imaging using a breath
      hold technique is usually used for dynamic studies and hepatobiliary phase Gd-EOB
      DTPA-enhanced magnetic resonance imaging (MRI). In cases where the patient has
      difficulty holding their breath, this scanning method can be difficult. PURPOSE:
      To investigate the usefulness of a fat-saturated T1-weighted spin-echo (SE)
      sequence using a radial read-out (radial acquisition regime-SE, RADAR-SE) during
      free breathing for hepatobiliary phase Gd-EOB-DTPA-enhanced MRI. MATERIAL AND
      METHODS: Images were acquired at 1.5 T. First, a phantom with diluted Gd-EOB-DTPA
      was scanned using the TIGRE sequence and the RADAR-SE sequence. Contrast ratios
      of the sequences were compared. Next, the hepatobiliary phase was imaged in 62
      patients using the TIGRE sequence with breath-hold and the RADAR-SE during free
      breathing. Qualitative and quantitative evaluations were compared. RESULTS: In
      the phantom study, RADAR-SE had a higher contrast ratio than TIGRE. In the
      clinical study, artifacts were more conspicuous in RADAR-SE compared to TIGRE
      images in the qualitative evaluation. However, RADAR-SE images were equal to or
      better than TIGRE images in patients who had difficulty holding their breath. The
      signal intensity ratio of the liver was statistically higher using RADAR-SE than
      TIGRE. CONCLUSION: RADAR-SE can be useful for hepatobiliary phase Gd-EOB-DTPA
      enhanced MRI in patients who have difficulty holding their breath.

PMID- 23873887
TI  - Pulmonary involvement in rheumatoid arthritis: multidetector computed tomography
      findings.
AB  - BACKGROUND: Pulmonary involvement in rheumatoid arthritis (RA) is common and
      encompasses a large spectrum of disease with different treatment options and
      prognoses. Therefore, assessment of these patients with multidetector computed
      tomography (MDCT) is vital. PURPOSE: To evaluate the MDCT pulmonary findings of
      patients with RA and to compare these findings with the clinical status. MATERIAL
      AND METHODS: Chest MDCT scans of 85 patients with RA between 2006-2012 were
      assessed. One patient with a pulmonary infection was excluded from the study.
      MDCT findings and distribution of the CT findings were examined, and patients
      were classified according to the predominant CT pattern. The pulmonary function
      test (PFT) results and categories, demographic characteristics, and clinical
      status of some of the patients for whom the results were obtained were evaluated,
      and the CT findings, PFT results, demographic characteristics, and clinical
      status were compared. RESULTS: The study group consisted of 20 men (mean age,
      58.1 years +/- 13.1; range, 15-77 years) and 64 women (mean age, 55.3 years +/-
      11.5; range, 30-84 years). The most frequent findings were nodules (78.6%) and
      pleural thickening (48.8%). The most common CT patterns were follicular
      bronchiolitis (FB) in 28 (33.3%) patients and nodular disease (ND) in 12 (14.3%)
      others. There was no statistically significant difference between the CT findings
      and PFT results, and no statistically significant difference was noted in the CT
      findings between symptomatic and asymptomatic patients. In addition, there were
      some patients who exhibited no symptoms and/or had abnormal PFT results but had
      abnormal CT findings. CONCLUSION: Rheumatoid arthritis is associated with a high
      frequency of CT findings and CT patterns, with nodules and pleural thickening
      being the most common CT findings and FB and ND being the most common CT
      patterns. MDCT identification of patients with RA may be helpful in the
      evaluation of pulmonary disease, even in patients without symptoms and PFT
      abnormalities.

PMID- 23873888
TI  - Quantitative evaluation of the axonal degeneration of central motor neurons in
      chronic cerebral stroke with diffusion tensor imaging.
AB  - BACKGROUND: Conventional magnetic resonance imaging (MRI) can only show the
      degeneration-induced morphological changes but fail to quantitatively reveal the
      degree and extent of the axonal damage of nerve fibers. Diffusion tensor imaging
      (DTI) has the ability to detect the diffusion of water molecules and thus
      suitable to the study of axonal degeneration of central motor neurons. PURPOSE:
      To illustrate and quantitatively evaluate the axonal degeneration of central
      motor neurons in patients with chronic cerebral stroke. MATERIAL AND METHODS: DTI
      and conventional MRI were carried out with 10 normal control subjects and 25
      patients who suffered from chronic cerebral stroke in the region supplied by
      middle cerebral artery and had varying degrees of limb movement disorders (the
      mean time of onset was 2.5 months), to measure the fractional anisotropy (FA),
      volume ratio (VR), apparent diffusion coefficient (ADC), tensor eigenvalues
      (lambda1, lambda2, and lambda3), and signal intensity (SI) on T2-weighted images,
      of the central motor fibers (pyramidal tract) in the plane of cerebral peduncle.
      Results from the ipsilateral side were compared with those from the contralateral
      side in the same patient and with those from normal control. RESULTS: The axonal
      degeneration of central motor neurons manifests in DTI as the decline of FA of
      the pyramidal tract and the reduction and distortion of the high signal area.
      While all the FA, VR, ADC, and lambda1 in the ipsilateral side reduce on DTI,
      lambda3 increases; the T2-weighted signals exhibit no significant differences
      among groups. CONCLUSION: The changes and diffusions of water molecule associated
      with the axonal degeneration of central motor neurons after chronic cerebral
      stroke can be detected by DTI, which can directly quantitatively reflect the
      degree and extent of axonal degeneration of central motor neurons and can
      compensate the shortcomings of conventional MRI and diffusion-weighted imaging
      (DWI).

PMID- 23873889
TI  - 2D versus 3D roadmap for uterine artery catheterization: impact on several
      angiographic parameters.
AB  - BACKGROUND: Three-dimensional (3D) roadmap is a recently developed imaging
      technique used to guide diagnostic and interventional catheter-directed
      procedures and mainly evaluated for neurovascular procedures. Few data with
      regard to efficacy and radiation dose are currently available in literature.
      PURPOSE: To evaluate the use of 3D roadmap technique as compared with the
      conventional two-dimensional (2D) roadmap for uterine artery catheterization and
      embolization during uterine fibroid embolization and assess the potential impact
      on radiation dose, contrast load, and total procedure time. MATERIAL AND METHODS:
      In this prospective study, 40 patients were randomly assigned to the 2D or 3D
      roadmap technique for uterine artery catheterization. Demographic data,
      specifically the patient's age, weight, height, pelvic circumference, and total
      uterine and fibroid volume were recorded. Exposure parameters, contrast load, and
      procedure time were recorded and organ doses for ovaries and uterus were
      calculated. RESULTS: Demographic data did not differ between the groups.
      Catheterization and embolization of both uterine arteries were feasible in all
      patients, although in one patient in the 3D group, a focal dissection of the
      proximal uterine artery occurred. No significant difference in estimated ovarian
      dose was found in the 3D versus 2D group (P = 0.07). Total procedure time was
      shorter in the 2D group (P = 0.01) and no difference in total contrast load was
      seen (P = 0.17). CONCLUSION: Both roadmap techniques are effective imaging-guided
      tools for uterine artery catheterization, without difference in terms of
      radiation exposure or contrast load. The total procedure time is shorter in the
      2D group.

PMID- 23873890
TI  - Breast reduction scars: a prospective survey of patient preferences.
AB  - BACKGROUND: Studies have shown that scarring is a primary reason for patient
      dissatisfaction with reduction mammaplasty. OBJECTIVES: The authors prospectively
      evaluated patient preferences for the 3 most common breast reduction scar
      patterns: horizontal, vertical, and Wise. METHODS: Sixty-six patients were
      recruited for the study before receiving their reduction mammaplasty
      consultation. Each patient was shown line drawings and postoperative photographs
      of the 3 breast reduction techniques and scored the scars on a modified 10-point
      Likert scale (1 = unacceptable; 10 = acceptable). The survey responses had no
      impact on the patients' medical care. A nonparametric Friedman test was used to
      compare the mean scores, and univariate generalized linear regression analysis
      was performed to adjust for confounding factors. Post hoc analysis was performed
      using the Bonferroni method. Significance was set at P < .001. RESULTS: Sixty
      patients completed the study. The mean preference ranking was significantly
      higher for the horizontal scar pattern versus vertical and Wise (P < .001). The
      mean score difference between the horizontal and Wise patterns was 2.982. The
      mean difference between the horizontal and vertical patterns was 2.27. There was
      no significant difference in preference between the vertical and Wise patterns.
      Linear regression analysis showed that age, body mass index, and torso/bra size
      had no significant effect on preference. CONCLUSIONS: To our knowledge, this is
      the first study designed to prospectively evaluate patient preferences regarding
      postoperative scars. Results indicate that the horizontal technique is preferable
      with respect to scar placement.

PMID- 23873891
TI  - Patient-reported outcomes of bimatoprost for eyelash growth: results from a
      randomized, double-masked, vehicle-controlled, parallel-group study.
AB  - BACKGROUND: Hypotrichosis of the eyelashes may negatively influence an
      individual's self-perception and appearance. Assessing the impact of treatment
      from a patient's perspective may be particularly relevant in trials of aesthetic
      agents. Once-daily dermal (topically applied) administration of bimatoprost
      ophthalmic solution 0.03% has been associated with increased eyelash prominence
      (ie, length, thickness, darkness). OBJECTIVES: The authors assess patient
      reported outcomes (PRO) after treatment with bimatoprost for hypotrichosis of the
      eyelashes. METHODS: In this multicenter, double-masked, randomized, vehicle
      controlled, parallel clinical trial, 4 PRO questionnaires were distributed to 278
      patients (bimatoprost [n = 137] and vehicle [n = 141]). The primary PRO
      questionnaire was the 23-item Eyelash Satisfaction Questionnaire (ESQ), which
      measured satisfaction in 3 domains: length, fullness, and overall satisfaction
      (LFOS); confidence, attractiveness, and professionalism (CAP); and impact on
      daily routine (DR). RESULTS: By week 16, the bimatoprost group reported
      significantly greater improvements from baseline on all ESQ items (P <= .0433).
      These improvements were sustained through the 4-week posttreatment study visit.
      Patient satisfaction was significantly greater in the bimatoprost group than in
      the vehicle group for all 3 domains: LFOS (weeks 8-20; P <= .0052), CAP (weeks 12
      20; P < .0001), and DR (weeks 16 and 20; P <= .01). CONCLUSIONS: The bimatoprost
      group reported significantly greater levels of positive patient outcomes and
      satisfaction than the vehicle group across all 23 questions and all 3 domains of
      the primary PRO questionnaire. These results support the effectiveness, as
      measured by objective measures and PRO, of once-daily bimatoprost ophthalmic
      solution 0.03% at producing more prominent eyelashes in adults.

PMID- 23873892
TI  - Testing for presence of known and unknown molecules in imaging mass spectrometry.
AB  - MOTIVATION: Imaging mass spectrometry has emerged in the past decade as a label
      free, spatially resolved and multi-purpose bioanalytical technique for direct
      analysis of biological samples. However, solving two everyday data analysis
      problems still requires expert judgment: (i) the detection of unknown molecules
      and (ii) the testing for presence of known molecules. RESULTS: We developed a
      measure of spatial chaos of a molecular image corresponding to a mass-to-charge
      value, which is a proxy for the molecular presence, and developed methods solving
      considered problems. The statistical evaluation was performed on a dataset from a
      rat brain section with test sets of molecular images selected by an expert. The
      measure of spatial chaos has shown high agreement with expert judges. The method
      for detection of unknown molecules allowed us to find structured molecular images
      corresponding to spectral peaks of any low intensity. The test for presence
      applied to a list of endogenous peptides ranked them according to the proposed
      measure of their presence in the sample. AVAILABILITY: The source code and test
      sets of mass-to-charge images are available at http://www.math.uni
      bremen.de/~theodore. SUPPLEMENTARY INFORMATION: Supplementary materials are
      available at Bioinformatics online. CONTACT: theodore@uni-bremen.de.

PMID- 23873893
TI  - Improving medication administration safety in solid organ transplant patients
      through barcode-assisted medication administration.
AB  - Solid organ transplant recipients are prescribed a high number of medications,
      increasing the potential for medication errors. Barcode-assisted medication
      administration (BCMA) is technology that reduces medication administration
      errors. An observational study was conducted at an academic medical center solid
      organ transplant unit before and after BMCA implementation. Medication accuracy
      was determined and administration errors were categorized by type and therapeutic
      class of medication. A baseline medication administration error rate of 4.8% was
      observed with wrong dose errors representing 78% of the errors. During the post
      BCMA period the medication administration error rate was reduced by 68% to 1.5%
      (P = .0001). Wrong dose errors were reduced by 67% (P = .001), and unauthorized
      medication administrations were reduced by 73%. Steroids were associated with the
      highest error rate. The results of this study suggest that routinely adopting
      BCMA has the potential to reduce medication administration errors in transplant
      patients. 

PMID- 23873894
TI  - Inferring gene networks from discrete expression data.
AB  - The modeling of gene networks from transcriptional expression data is an
      important tool in biomedical research to reveal signaling pathways and to
      identify treatment targets. Current gene network modeling is primarily based on
      the use of Gaussian graphical models applied to continuous data, which give a
      closed-form marginal likelihood. In this paper, we extend network modeling to
      discrete data, specifically data from serial analysis of gene expression, and RNA
      sequencing experiments, both of which generate counts of mRNA transcripts in cell
      samples. We propose a generalized linear model to fit the discrete gene
      expression data and assume that the log ratios of the mean expression levels
      follow a Gaussian distribution. We restrict the gene network structures to
      decomposable graphs and derive the graphs by selecting the covariance matrix of
      the Gaussian distribution with the hyper-inverse Wishart priors. Furthermore, we
      incorporate prior network models based on gene ontology information, which avails
      existing biological information on the genes of interest. We conduct simulation
      studies to examine the performance of our discrete graphical model and apply the
      method to two real datasets for gene network inference.

PMID- 23873895
TI  - Sample size requirements for training high-dimensional risk predictors.
AB  - A common objective of biomarker studies is to develop a predictor of patient
      survival outcome. Determining the number of samples required to train a predictor
      from survival data is important for designing such studies. Existing sample size
      methods for training studies use parametric models for the high-dimensional data
      and cannot handle a right-censored dependent variable. We present a new training
      sample size method that is non-parametric with respect to the high-dimensional
      vectors, and is developed for a right-censored response. The method can be
      applied to any prediction algorithm that satisfies a set of conditions. The
      sample size is chosen so that the expected performance of the predictor is within
      a user-defined tolerance of optimal. The central method is based on a pilot
      dataset. To quantify uncertainty, a method to construct a confidence interval for
      the tolerance is developed. Adequacy of the size of the pilot dataset is
      discussed. An alternative model-based version of our method for estimating the
      tolerance when no adequate pilot dataset is available is presented. The model
      based method requires a covariance matrix be specified, but we show that the
      identity covariance matrix provides adequate sample size when the user specifies
      three key quantities. Application of the sample size method to two microarray
      datasets is discussed. 

PMID- 23873896
TI  - Optimisation of prescription in patients with long-term treatment-resistant
      schizophrenia.
AB  - OBJECTIVE: The aim of this clinical review was to investigate the effectiveness
      and safety of the practice of antipsychotic poly-pharmacy (AP) in the long-term
      management of hospitalised patients with insufficient response to antipsychotic
      monotherapy. METHOD: The databases Medline, PsycINFO, Embase and Scopus were
      searched. Studies were required to include inpatients with long-term, treatment
      resistant schizophrenia on maintenance AP. The search was restricted to
      systematic review studies. RESULTS: The review yielded four studies of interest
      that showed no categorical advantage for maintenance AP for the population of
      interest. However, clozapine combination faired marginally well. Particular
      weaknesses of the present literature are low number of participants, and
      inadequate monitoring of potential adverse effects. The evidence on the risks and
      benefits of maintenance AP is not generally considered adequate to warrant a
      recommendation for its use in routine clinical practice in psychiatry.
      CONCLUSIONS: This review provides a synthesis of the evidence on the maintenance
      use of AP for hospitalised patients with long-term, treatment-resistant
      schizophrenia. The results show both no support for AP with some marginal benefit
      for clozapine combination therapy, and methodological weaknesses of the included
      studies. These findings have clinical implications for treatment decisions and
      suggest that sufficiently powered studies are needed.

PMID- 23873897
TI  - The role of trainees as clinical teachers of medical students in psychiatry.
AB  - OBJECTIVE: To consider the role of specialty trainees as clinical teachers of
      medical students in psychiatry. METHOD: We discuss the role of specialty trainees
      as teachers and approaches to improving their skills and capacity, giving
      examples from the local and international literature and our own experience as
      psychiatry medical educators. RESULTS: Good clinical teaching is crucial for
      medical students' learning but sharp increases in numbers combined with economic
      and workforce pressures have stretched capacity. Specialty trainees do much of
      the medical student teaching during their clinical placements but infrequently
      receive instruction on how to teach. The two common approaches to increasing
      capacity are, first, establishing education rotations for individual trainees
      and, second, providing workshops to improve trainees' confidence and skill.
      Psychiatry trainees surveyed in New South Wales welcomed the role of teacher and
      the opportunity to improve their teaching capacity. Further support from
      supervisors, health services and medical schools is needed to assist trainees in
      their teaching role. CONCLUSION: The role that trainees play as clinical teachers
      should be acknowledged and supported. Further development of research and
      scholarship in medical education is needed to determine how best to teach
      trainees to teach.

PMID- 23873898
TI  - Hypoxic pulmonary hypertension; the load on the right ventricle. Introduction.

PMID- 23873899
TI  - The role of cGMP in the physiological and molecular responses of the right
      ventricle to pressure overload.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease that is associated
      with a poor prognosis and results in right heart dysfunction. While pulmonary
      vascular disease is the obvious primary pathological focus, right ventricular
      hypertrophy (RVH) and right ventricular (RV) dysfunction are major determinants
      of prognosis in PAH. Our knowledge about the molecular physiology and
      pathophysiology of RV hypertrophy and failure in response to pressure overload is
      still limited, and most data are derived from left heart research. However, the
      molecular mechanisms of left ventricular remodelling cannot be generalized to the
      RV, because the right and left ventricles differ greatly in their size, shape,
      architecture and function. Despite the recent advances in diagnosis and treatment
      of PAH, little is known about the molecular and cellular mechanisms that underlie
      the transition from compensatory to maladaptive RV remodelling. The cGMP
      phosphodiesterase 5 (PDE5) pathway is one of the extensively studied pathways in
      PAH, but our knowledge about cGMP-PDE5 signalling in RV pathophysiology is still
      limited. For this purpose, there is need for animal models that can represent
      changes in the RV that closely mimic the human situation. The availability of an
      animal model of pressure-overload-induced RVH (e.g. pulmonary artery banding
      model) provides us with a valuable tool to understand the differences between
      adaptive and maladaptive RVH and to explore the direct effects of current PAH
      therapy on the heart. In this report, we discuss myocardial regulatory effects of
      cGMP-PDE5 signalling in preclinical models of RV pressure overload for
      understanding the physiological/pathophysiological mechanisms involved in
      maladaptive RVH. 

PMID- 23873901
TI  - A randomised controlled trial of ranibizumab with and without ketorolac eyedrops
      for exudative age-related macular degeneration.
AB  - AIMS: To evaluate whether ketorolac eyedrops and ranibizumab intravitreal
      injections would provide additional benefit over ranibizumab alone in the
      treatment of choroidal neovascularisation (CNV). METHODS: This was a pilot study
      of eyes with new-onset CNV. A total of 56 patients were enrolled consecutively
      and randomised in a 1:1 ratio to receive combination treatment with intravitreal
      ranibizumab and topical ketorolac (group 1) or ranibizumab alone (group 2). All
      patients received monthly 0.5-mg ranibizumab intravitreal injections for 3
      months, after which monthly injections were administered in accordance with the
      standard of care. Group 1 patients also self-administered one drop of ketorolac
      three times a day for 6 months. All patients were followed up for 6 months.
      RESULTS: At 6 months, both groups showed a significant improvement in best
      corrected visual acuity (both, p<0.001). The two treatments did not show
      significant differences in terms of the number of ranibizumab injections
      required. However, the mean 6-month change in central macular thickness (CMT) in
      the combination group was -124 um (-29.7%; p<0.001), while in the ranibizumab
      only group, the change was -86.9 um (-19.5%; p=0.001); thus, the combination
      treatment resulted in a greater reduction (p=0.003). The combination treatment
      had no adverse effects. CONCLUSIONS: This pilot study is the first to
      prospectively investigate the efficacy and safety of a combination of 0.45%
      ketorolac eyedrops three times a day and intravitreal ranibizumab injections in
      patients with CNV, and suggests that topical ketorolac supplements the activity
      of intravitreal ranibizumab in reducing CMT in CNV.

PMID- 23873902
TI  - Prevalence of chronic diseases at the onset of inflammatory arthritis: a
      population-based study.
AB  - OBJECTIVE: Little is known about the presence of chronic morbidity in
      inflammatory arthritis (IA) patients at disease onset. Previous studies have been
      mainly performed in established IA patients or they focus on isolated co-morbid
      diseases. Our aim was to determine the prevalence of chronic diseases at the
      onset of IA and to determine whether this is different from the number that one
      might expect based on age and sex. Patients and methods. A nested case-control
      study from 2001 to 2010 using data from patient electronic medical records in
      general practice. Totally, 3354 patients with newly diagnosed IA were included.
      Each patient was matched on age, sex and general practice with two control
      patients. In total, 121 different chronic diseases were studied. RESULTS: In
      total, 70% of the IA patients had at least one chronic disease at the onset of
      IA, compared with 59% of the control patients (P < 0.001). The highest prevalence
      in IA patients was found for cardiovascular diseases (35%), musculoskeletal
      diseases (27%) and neurological diseases (22%). Compared with the control
      patients, patients with IA had the highest increased risk for musculoskeletal
      diseases [odds ratio, OR = 1.7 (95% confidence interval: 1.6-19)] and for
      neurological diseases [OR = 1.6 (1.4-1.7)] at the onset of IA. CONCLUSION: At the
      onset of IA, nearly three-quarters of patients with IA had at least one other
      chronic disease. Since multi-morbidity affects treatment and outcome of the IA
      patient, these diseases should be taken into account when treating IA patients.

PMID- 23873903
TI  - Focal nodular hyperplasia: characterisation at gadoxetic acid-enhanced MRI and
      diffusion-weighted MRI.
AB  - PURPOSE: The aim of this study was to assess the enhancement patterns of hepatic
      focal nodular hyperplasia (FNH) on gadoxetic acid-enhanced MRI and diffusion
      weighted (DW) MRI. METHODS: This retrospective study had institutional review
      board approval. Gadoxetic acid-enhanced and DW MR images were evaluated in 23
      patients with 30 FNHs (26 histologically proven and 4 radiologically diagnosed).
      The lesion enhancement patterns of the hepatobiliary phase images were classified
      as heterogeneous or homogeneous signal intensity (SI), and as dominantly high/iso
      or low SI compared with those of adjacent liver parenchyma. Heterogeneous (any)
      SI lesions and homogeneous low SI lesions were categorised into the fibrosis
      group, whereas homogeneous high/iso SI lesions were categorised into the non
      fibrosis group. Additionally, lesion SI on T2 weighted images, DW images and
      apparent diffusion coefficient (ADC) values were compared between the two groups.
      RESULTS: The lesions showed heterogeneous high/iso SI (n=16), heterogeneous low
      SI (n=5), homogeneous high/iso SI (n=7) or homogeneous low SI (n=2) at the
      hepatobiliary phase MR images. The fibrosis group lesions were more likely to
      show high SI on DW images and T2 weighted images compared with those in the non
      fibrosis group (p<0.05). ADC values tended to be lower in the fibrosis group than
      those in the non-fibrosis group without significance. CONCLUSION: FNH showed
      variable enhancement patterns on hepatobiliary phase images during gadoxetic acid
      enhanced MRI. SI on DW and T2 weighted images differed according to the fibrosis
      component contained in the lesion. ADVANCES IN KNOWLEDGE: FNH shows a wide
      spectrum of imaging findings on gadoxetic acid-enhanced MRI and DW MRI.

PMID- 23873904
TI  - MDCT features in the differentiation of T4a gastric cancer from less-advanced
      gastric cancer: significance of the hyperattenuating serosa sign.
AB  - OBJECTIVE: The purpose of our study was to evaluate CT findings to differentiate
      between T4a and less advanced gastric cancers. METHODS: The institutional review
      board approved this study and waived informed consent. This study included 228
      retrospectively identified patients with surgically confirmed gastric cancer (138
      T1, 25 T2, 24 T3 and 41 T4a) and who had also undergone pre-operative CT scan.
      Transverse and multiplanar reconstruction scans were reviewed in consensus by two
      other blinded radiologists. The following CT findings that differentiate T4a from
      less advanced cancers were evaluated: nodular or an irregular outer layer of the
      gastric wall, haziness of the perigastric fat and a hyperattenuating serosa sign.
      The CT features of T4a and less advanced gastric cancers were compared by means
      of univariate and multivariate analyses. RESULTS: In univariate analysis, nodular
      or an irregular outer layer of the gastric wall, haziness of the perigastric fat
      and the hyperattenuating serosa sign were significant in differentiation between
      T4a and less advanced gastric cancers. In addition, nodular or an irregular outer
      layer of the gastric wall and the hyperattenuating serosa sign were significant
      in differentiation between T3 and T4a. In multivariate logistic analysis, the
      hyperattenuating serosa sign was the most significant finding in differentiation
      between T3 and T4a (odds ratio, 4.210; 95% confidence intervals, 1.581-11.214;
      p=0.004). CONCLUSION: The hyperattenuating serosa sign may be a useful CT finding
      in differentiation between T4a and less-advanced gastric cancers. ADVANCES IN
      KNOWLEDGE: The hyperattenuating serosa sign is associated with gastric cancer
      with invading the serosa and can facilitate planning of the optimal pre-operative
      evaluation and treatment.

PMID- 23873905
TI  - A comparison of free-hand vs laser-guided long-axis ultrasound techniques in
      novice users.
AB  - OBJECTIVE: The increasing use of point-of-care ultrasonography for targeted
      procedures justifies a device that helps both novices in training and experts
      perform the long-axis needle approach. The initial success of traditional needle
      guidance devices in reducing the time of target procedures is not universal and
      they can be cumbersome. We aim to investigate whether the less bulky and
      previously untested laser guide can succeed in reducing procedure time in novice
      ultrasonographers. METHODS: 82 medical students with no ultrasound experience
      volunteered. Random allocation determined whether, during a targeted procedure in
      a turkey breast and olive phantom, participants were assisted by the laser guide
      or not. The time taken to pierce the target was recorded at 1-cm depth. RESULTS:
      The mean procedure time in the laser-assisted (LA) group was 25.1 s (14.0 s; 18.0
      25.0 s). The mean procedure time in the free-hand group was 45.5 s (23.0 s; 7.0
      55.0 s). The procedure time in the LA group was significantly reduced (p<0.01).
      CONCLUSION: The laser guide significantly improved procedure times. It is felt
      that the cheaper, smaller, easy to integrate, sterile and more user-friendly
      laser guidance unit may be a better alternative to the needle guide in improving
      procedure times for the novice ultrasonographer or to assist the expert, during
      training for, or performance of, ultrasound-guided targeted procedures. ADVANCES
      IN KNOWLEDGE: Following from the prototype paper, this is the first study to
      investigate the effectiveness of attaching a laser-guidance device to an
      ultrasound probe. The device succeeded in reducing the procedure times of
      targeted procedures.

PMID- 23873906
TI  - Stereotactic ablative radiotherapy in the UK: current status and developments.
AB  - Stereotactic ablative radiotherapy (SABR) has developed from the principles and
      techniques used in the stereotactic radiosurgery treatment of brain metastases.
      Advances in computer technology, imaging, planning and treatment delivery and
      evidence from retrospective analysis of single- and multi-institutional early
      phase studies have established SABR in the treatment of medically inoperable
      early lung cancer. Effective multidisciplinary team working is crucial to safe
      delivery of SABR. The variation in patient selection, radiotherapy planning and
      delivery techniques has led to a collective approach to SABR implementation
      across the UK. Centres developing the technique are represented in the UK SABR
      Consortium, which is supported by the relevant UK professional bodies and
      represents a platform to develop extracranial SABR across the UK. The uptake of
      SABR in the UK has been slowed by workforce issues, but at least 15 centres are
      currently delivering treatment with over 500 patients treated using UK SABR
      Consortium guidance. A mentoring program is being piloted helping new centres to
      develop their programs, and over 30 UK centres are expected to be offering SABR
      treatment by the end of 2014. The use of consistent guidance for patient
      selection, treatment planning and delivery in the UK gives the opportunity to
      collect and audit toxicity and outcome across the centres, contributing to the
      internationally reported SABR experience. Having established this service in the
      UK, the development of SABR through clinical research is a priority, and with
      input from the Radiotherapy Trials Quality Assurance Group, the UK is developing
      a national study program that includes participation in international trials. 

PMID- 23873907
TI  - Video-EEG recordings in full-term neonates of diabetic mothers: observational
      study.
AB  - OBJECTIVE: To determine whether full-term newborn infants of diabetic mothers
      (IDM) present immature/disorganised EEG patterns in the immediate neonatal
      period, and whether there was any relationship with maternal glycaemic control.
      DESIGN AND SETTING: Cohort study with an incidental sample performed in a
      tertiary hospital neonatal unit. PATIENTS: 23 IDM and 22 healthy newborns born
      between 2010 and 2013. INTERVENTIONS: All underwent video-EEG recording lasting
      >90 min at 48-72 h of life. MAIN OUTCOME MEASURES: We analysed the percentage of
      indeterminate sleep, transient sharp waves per hour and mature-for-gestational
      age EEG patterns (discontinuity, maximum duration of interburst interval (IBI),
      asynchrony, asymmetry, delta brushes, encoches frontales and alpha/theta rolandic
      activity). The group of IDM was divided into two subgroups according to maternal
      HbA1c: (1) HbA1c>=6% and (2) HbA1c<6%. RESULTS: Compared with healthy newborns,
      IDM presented significantly higher percentage of indeterminate sleep (57% vs 25%;
      p<0.001), discontinuity (2.5% vs 0%; p=0.044) and delta brushes in the bursts (6%
      vs 3%; p=0.024); higher duration of IBI (0.3 s vs 0 s; p=0.017); fewer encoches
      frontales (7/h vs 35/h; p<0.001), reduced theta/alpha rolandic activity (3/h vs
      9/h; p<0.001); and more transient sharp waves (25/h vs 5/h; p<0.001). IDM with
      maternal HbA1c>=6% showed greater percentage of delta brushes in the burst (14%
      vs 4%; p=0.007). CONCLUSIONS: Full-term IDM newborns showed video-EEG features of
      abnormal development of brain function. Maternal HbA1c levels<6% during pregnancy
      could minimise the risk of cerebral dysmaturity.

PMID- 23873908
TI  - Identification and characterization of Clostridium sordellii toxin gene
      regulator.
AB  - Toxigenic Clostridium sordellii causes uncommon but highly lethal infections in
      humans and animals. Recently, an increased incidence of C. sordellii infections
      has been reported in women undergoing obstetric interventions. Pathogenic strains
      of C. sordellii produce numerous virulence factors, including sordellilysin,
      phospholipase, neuraminidase, and two large clostridial glucosylating toxins,
      TcsL and TcsH. Recent studies have demonstrated that TcsL toxin is an essential
      virulence factor for the pathogenicity of C. sordellii. In this study, we
      identified and characterized TcsR as the toxin gene (tcsL) regulator in C.
      sordellii. High-throughput sequencing of two C. sordellii strains revealed that
      tcsR lies within a genomic region that encodes TcsL, TcsH, and TcsE, a putative
      holin. By using ClosTron technology, we inactivated the tcsR gene in strain ATCC
      9714. Toxin production and tcsL transcription were decreased in the tcsR mutant
      strain. However, the complemented tcsR mutant produced large amounts of toxins,
      similar to the parental strain. Expression of the Clostridium difficile toxin
      gene regulator tcdR also restored toxin production to the C. sordellii tcsR
      mutant, showing that these sigma factors are functionally interchangeable. 

PMID- 23873909
TI  - H-NS is a novel transcriptional modulator of the ribonucleotide reductase genes
      in Escherichia coli.
AB  - Ribonucleotide reductases (RNRs) are essential enzymes for DNA synthesis because
      they are responsible for the production of the four deoxyribonucleotides (dNTPs)
      from their corresponding ribonucleotides. Escherichia coli contains two classes
      of aerobic RNRs, encoded by the nrdAB (class Ia) and nrdHIEF (class Ib) operons,
      and a third RNR class, which is functional under anaerobic conditions and is
      encoded by the nrdDG (class III) operon. Because cellular imbalances in the
      amounts of the four dNTPs cause an increase in the rate of mutagenesis, the
      activity and the expression of RNRs must be tightly regulated during bacterial
      chromosome replication. The transcriptional regulation of these genes requires
      several transcription factors (including DnaA, IciA, FIS [factor for inversion
      stimulation], Fnr, Fur, and NrdR), depending on the RNR class; however, the
      factors that dictate the expression of some RNR genes in response to different
      environmental conditions are not known. We show that H-NS modulates the
      expression of the nrdAB and nrdDG operons. H-NS represses expression both in
      aerobically and in anaerobically growing cells. Under aerobic conditions,
      repression occurs at the exponential phase of growth as well as at the transition
      from the exponential to the stationary phase, a period when no dNTPs are needed.
      Under anoxic conditions, repression occurs mainly in exponentially growing cells.
      Electrophoretic mobility assays performed with two DNA fragments from the
      regulatory region of the nrdAB operon demonstrated the direct interaction of H-NS
      with these sequences. 

PMID- 23873910
TI  - RflM functions as a transcriptional repressor in the autogenous control of the
      Salmonella Flagellar master operon flhDC.
AB  - Motility of bacteria like Salmonella enterica is a highly regulated process that
      responds to a variety of internal and external stimuli. A hierarchy of three
      promoter classes characterizes the Salmonella flagellar system, and the onset of
      flagellar gene expression depends on the oligomeric regulatory complex and class
      1 gene product FlhD(4)C(2). The flhDC promoter is a target for a broad range of
      transcriptional regulators that bind within the flhDC promoter region and either
      negatively or positively regulate flhDC operon transcription. In this work, we
      demonstrate that the RflM protein is a key component of flhDC regulation.
      Transposon mutagenesis was performed to investigate a previously described
      autoinhibitory effect of the flagellar master regulatory complex FlhD(4)C(2).
      RflM is a LuxR homolog that functions as a flagellar class 1 transcriptional
      repressor. RflM was found to be the negative regulator of flhDC expression that
      is responsible for the formerly described autoinhibitory effect of the
      FlhD(4)C(2) complex on flhDC operon transcription (K. Kutsukake, Mol. Gen. Genet.
      254:440-448, 1997). We conclude that upon commencement of flagellar gene
      expression, the FlhD(4)C(2) complex initiates a regulatory feedback loop by
      activating rflM gene expression. rflM encodes a transcriptional repressor, RflM,
      which fine-tunes flhDC expression levels.

PMID- 23873911
TI  - Physiological consequences of multiple-target regulation by the small RNA SgrS in
      Escherichia coli.
AB  - Cells use complex mechanisms to regulate glucose transport and metabolism to
      achieve optimal energy and biomass production while avoiding accumulation of
      toxic metabolites. Glucose transport and glycolytic metabolism carry the risk of
      the buildup of phosphosugars, which can inhibit growth at high concentrations.
      Many enteric bacteria cope with phosphosugar accumulation and associated stress
      (i.e., sugar-phosphate stress) by producing a small RNA (sRNA) regulator, SgrS,
      which decreases phosphosugar accumulation in part by repressing translation of
      sugar transporter mRNAs (ptsG and manXYZ) and enhancing translation of a sugar
      phosphatase mRNA (yigL). Despite a molecular understanding of individual target
      regulation by SgrS, previously little was known about how coordinated regulation
      of these multiple targets contributes to the rescue of cell growth during sugar
      phosphate stress. This study examines how SgrS regulation of different targets
      impacts growth under different nutritional conditions when sugar-phosphate stress
      is induced. The severity of stress-associated growth inhibition depended on
      nutrient availability. Stress in nutrient-rich media necessitated SgrS regulation
      of only sugar transporter mRNAs (ptsG or manXYZ). However, repression of
      transporter mRNAs was insufficient for growth rescue during stress in nutrient
      poor media; here SgrS regulation of the phosphatase (yigL) and as-yet-undefined
      targets also contributed to growth rescue. The results of this study imply that
      regulation of only a subset of an sRNA's targets may be important in a given
      environment. Further, the results suggest that SgrS and perhaps other sRNAs are
      flexible regulators that modulate expression of multigene regulons to allow cells
      to adapt to an array of stress conditions. 

PMID- 23873912
TI  - Gene content and diversity of the loci encoding biosynthesis of capsular
      polysaccharides of the 15 serovar reference strains of Haemophilus parasuis.
AB  - Haemophilus parasuis is the causative agent of Glasser's disease, a systemic
      disease of pigs, and is also associated with pneumonia. H. parasuis can be
      classified into 15 different serovars. Here we report, from the 15 serotyping
      reference strains, the DNA sequences of the loci containing genes for the
      biosynthesis of the group 1 capsular polysaccharides, which are potential
      virulence factors of this bacterium. We contend that these loci contain genes for
      polysaccharide capsule structures, and not a lipopolysaccharide O antigen,
      supported by the fact that they contain genes such as wza, wzb, and wzc, which
      are associated with the export of polysaccharide capsules in the current capsule
      classification system. A conserved region at the 3' end of the locus, containing
      the wza, ptp, wzs, and iscR genes, is consistent with the characteristic export
      region 1 of the model group 1 capsule locus. A potential serovar-specific region
      (region 2) has been found by comparing the predicted coding sequences (CDSs) in
      all 15 loci for synteny and homology. The region is unique to each reference
      strain with the exception of those in serovars 5 and 12, which are identical in
      terms of gene content. The identification and characterization of this locus
      among the 15 serovars is the first step in understanding the genetic, molecular,
      and structural bases of serovar specificity in this poorly studied but important
      pathogen and opens up the possibility of developing an improved molecular
      serotyping system, which would greatly assist diagnosis and control of Glasser's
      disease. 

PMID- 23873913
TI  - Genome-wide transcriptional profiling of the purple sulfur bacterium
      Allochromatium vinosum DSM 180T during growth on different reduced sulfur
      compounds.
AB  - The purple sulfur bacterium Allochromatium vinosum DSM 180(T) is one of the best
      studied sulfur-oxidizing anoxygenic phototrophic bacteria, and it has been
      developed into a model organism for laboratory-based studies of oxidative sulfur
      metabolism. Here, we took advantage of the organism's high metabolic versatility
      and performed whole-genome transcriptional profiling to investigate the response
      of A. vinosum cells upon exposure to sulfide, thiosulfate, elemental sulfur, or
      sulfite compared to photoorganoheterotrophic growth on malate. Differential
      expression of 1,178 genes was observed, corresponding to 30% of the A. vinosum
      genome. Relative transcription of 551 genes increased significantly during growth
      on one of the different sulfur sources, while the relative transcript abundance
      of 627 genes decreased. A significant number of genes that revealed strongly
      enhanced relative transcription levels have documented sulfur metabolism-related
      functions. Among these are the dsr genes, including dsrAB for dissimilatory
      sulfite reductase, and the sgp genes for the proteins of the sulfur globule
      envelope, thus confirming former results. In addition, we identified new genes
      encoding proteins with appropriate subcellular localization and properties to
      participate in oxidative dissimilatory sulfur metabolism. Those four genes for
      hypothetical proteins that exhibited the strongest increases of mRNA levels on
      sulfide and elemental sulfur, respectively, were chosen for inactivation and
      phenotypic analyses of the respective mutant strains. This approach verified the
      importance of the encoded proteins for sulfur globule formation during the
      oxidation of sulfide and thiosulfate and thereby also documented the suitability
      of comparative transcriptomics for the identification of new sulfur-related genes
      in anoxygenic phototrophic sulfur bacteria. 

PMID- 23873914
TI  - Complex regulation of the phosphoenolpyruvate carboxykinase gene pck and
      characterization of its GntR-type regulator IolR as a repressor of myo-inositol
      utilization genes in Corynebacterium glutamicum.
AB  - DNA affinity chromatography with the promoter region of the Corynebacterium
      glutamicum pck gene, encoding phosphoenolpyruvate carboxykinase, led to the
      isolation of four transcriptional regulators, i.e., RamA, GntR1, GntR2, and IolR.
      Determination of the phosphoenolpyruvate carboxykinase activity of the DeltaramA,
      DeltagntR1 DeltagntR2, and DeltaiolR deletion mutants indicated that RamA
      represses pck during growth on glucose about 2-fold, whereas GntR1, GntR2, and
      IolR activate pck expression about 2-fold irrespective of whether glucose or
      acetate served as the carbon source. The DNA binding sites of the four regulators
      in the pck promoter region were identified and their positions correlated with
      the predicted functions as repressor or activators. The iolR gene is located
      upstream and in a divergent orientation with respect to a iol gene cluster,
      encoding proteins involved in myo-inositol uptake and degradation. Comparative
      DNA microarray analysis of the DeltaiolR mutant and the parental wild-type strain
      revealed strongly (>100-fold) elevated mRNA levels of the iol genes in the
      mutant, indicating that the primary function of IolR is the repression of the iol
      genes. IolR binding sites were identified in the promoter regions of iolC, iolT1,
      and iolR. IolR therefore is presumably subject to negative autoregulation. A
      consensus DNA binding motif (5'-KGWCHTRACA-3') which corresponds well to those of
      other GntR-type regulators of the HutC family was identified. Taken together, our
      results disclose a complex regulation of the pck gene in C. glutamicum and
      identify IolR as an efficient repressor of genes involved in myo-inositol
      catabolism of this organism. 

PMID- 23873915
TI  - Redundant group a streptococcus signaling peptides exhibit unique activation
      potentials.
AB  - All bacterial quorum sensing (QS) systems are based on the production, secretion,
      and detection of small signaling molecules. Gram-positive bacteria typically use
      small peptides as QS effectors, and each QS circuit generally requires the
      interaction of a single signaling molecule with a single receptor protein. The
      recently described Rgg2 and Rgg3 (Rgg2/3) regulatory circuit of Streptococcus
      pyogenes (group A streptococcus [GAS]) is one of only a few QS circuits known to
      utilize multiple signaling peptides. In this system, two distinct, endogenously
      produced peptide pheromones (SHP2 and SHP3) both function to activate the QS
      circuit. The aim of this study was to further define the roles of SHP2 and SHP3
      in activation of the Rgg2/3 QS system, specifically with regard to shp gene
      identity and dosage. Results from our studies using transcriptional reporters and
      isogenic GAS mutants demonstrate that shp gene dosage does contribute to Rgg2/3
      system induction, as decreased gene dosage results in decreased or absent
      induction. Beyond this, however, data indicate that the shp genes possess
      distinct potentials for supporting system activation, with shp3 more readily able
      to support system activation than shp2. Studies using synthetic peptides and shp
      gene mutants indicate that the disparate activities of endogenous SHPs are due to
      production, rather than signaling, differences and are conferred by the N
      terminal regions rather than the C-terminal signaling regions of the peptides.
      These data provide evidence that the N-terminal, noneffector sequences of SHP
      pheromones influence their production efficiencies and thereby the relative
      activation potentials of endogenous SHPs. 

PMID- 23873916
TI  - Effects of low PBP2b levels on cell morphology and peptidoglycan composition in
      Streptococcus pneumoniae R6.
AB  - Streptococcus pneumoniae produces two class B penicillin-binding proteins, PBP2x
      and PBP2b, both of which are essential. It is generally assumed that PBP2x is
      specifically involved in septum formation, while PBP2b is dedicated to peripheral
      cell wall synthesis. However, little experimental evidence exists to substantiate
      this belief. In the present study, we obtained evidence that strongly supports
      the view that PBP2b is essential for peripheral peptidoglycan synthesis.
      Depletion of PBP2b expression gave rise to long chains of cells in which
      individual cells were compressed in the direction of the long axis and looked
      lentil shaped. This morphological change is consistent with a role for
      pneumococcal PBP2b in the synthesis of the lateral cell wall. Depletion of PBP2x,
      on the other hand, resulted in lemon-shaped and some elongated cells with a
      thickened midcell region. Low PBP2b levels gave rise to changes in the
      peptidoglycan layer that made pneumococci sensitive to exogenously added LytA
      during logarithmic growth and refractory to chain dispersion upon addition of
      LytB. Interestingly, analysis of the cell wall composition of PBP2b-depleted
      pneumococci revealed that they had a larger proportion of branched stem peptides
      in their peptidoglycan than the corresponding undepleted cells. Furthermore, MurM
      deficient mutants, i.e., mutants lacking the ability to synthesize branched
      muropeptides, were found to require much higher levels of PBP2b to sustain growth
      than those required by MurM-proficient strains. These findings might help to
      explain why increased incorporation of branched muropeptides is required for high
      level beta-lactam resistance in S. pneumoniae. 

PMID- 23873919
TI  - Effectiveness of pertussis vaccines for adolescents and adults: case-control
      study.
AB  - OBJECTIVE: To assess the effectiveness of reduced acellular pertussis (Tdap)
      vaccines in adolescents and adults. SETTING: Kaiser Permanente Northern
      California. DESIGN: Case-control study. PARTICIPANTS: All polymerase chain
      reaction (PCR) confirmed cases of pertussis in members aged 11 years and older
      from January 2006 to December 2011. We compared the Tdap vaccination status of
      PCR positive cases with two control groups: people testing negative for pertussis
      by PCR and closely matched people from the general Kaiser Permanente Northern
      California population. MAIN OUTCOME MEASURE: PCR confirmed pertussis. The
      association of Tdap vaccination with the odds of pertussis infection was
      estimated by conditional logistic regression, with adjustment for calendar time,
      pertussis vaccine type received in early childhood, age, sex, race or ethnic
      group, and medical clinic. We calculated Tdap vaccine effectiveness as 1 minus
      the adjusted odds ratio. RESULTS: The study population included 668 PCR positive
      cases, 10,098 PCR negative controls, and 21,599 Kaiser Permanente Northern
      California matched controls. Tdap vaccination rates were 24.0% in PCR positive
      cases and 31.9% in PCR negative controls (P<0.001). The adjusted estimate of
      effectiveness of Tdap vaccination against pertussis was 53.0% (95% confidence
      interval 41.9% to 62.0%) in the comparison with PCR controls, and 64.0% (55.5% to
      70.9%) in the comparison with Kaiser Permanente Northern California controls.
      CONCLUSION: Tdap vaccination was moderately effective at preventing PCR confirmed
      pertussis among adolescents and adults.

PMID- 23873920
TI  - A sixth of hospitals in England have expanded private patient options this year,
      the BMJ finds.

PMID- 23873918
TI  - Organellar inheritance in the green lineage: insights from Ostreococcus tauri.
AB  - Along the green lineage (Chlorophyta and Streptophyta), mitochondria and
      chloroplast are mainly uniparentally transmitted and their evolution is thus
      clonal. The mode of organellar inheritance in their ancestor is less certain. The
      inability to make clear phylogenetic inference is partly due to a lack of
      information for deep branching organisms in this lineage. Here, we investigate
      organellar evolution in the early branching green alga Ostreococcus tauri using
      population genomics data from the complete mitochondrial and chloroplast genomes.
      The haplotype structure is consistent with clonal evolution in mitochondria,
      while we find evidence for recombination in the chloroplast genome. The number of
      recombination events in the genealogy of the chloroplast suggests that
      recombination, and thus biparental inheritance, is not rare. Consistent with the
      evidence of recombination, we find that the ratio of the number of nonsynonymous
      to the synonymous polymorphisms per site is lower in chloroplast than in the
      mitochondria genome. We also find evidence for the segregation of two selfish
      genetic elements in the chloroplast. These results shed light on the role of
      recombination and the evolutionary history of organellar inheritance in the green
      lineage. 

PMID- 23873921
TI  - Pneumococcal vaccination programme followed by sustained declines in all cause
      pneumonia.

PMID- 23873922
TI  - Air pollution linked to acute heart failure.

PMID- 23873923
TI  - Cognition improves in successive birth cohorts of the oldest old.

PMID- 23873924
TI  - Termination no longer associated with preterm birth in Scotland.

PMID- 23873925
TI  - Hallucination.

PMID- 23873926
TI  - The dying deserve better from GPs.

PMID- 23873917
TI  - Comparison of metabolic capacities and inference of gene content evolution in
      mosquito-associated Spiroplasma diminutum and S. taiwanense.
AB  - Mosquitoes are hosts of several Spiroplasma species that belong to different
      serogroups. To investigate the genetic mechanisms that may be involved in the
      utilization of similar hosts in these phylogenetically distinct bacteria, we
      determined the complete genome sequences of Spiroplasma diminutum and S.
      taiwanense for comparative analysis. The genome alignment indicates that their
      chromosomal organization is highly conserved, which is in sharp contrast to the
      elevated genome instabilities observed in other Spiroplasma lineages. Examination
      of the substrate utilization strategies revealed that S. diminutum can use a wide
      range of carbohydrates, suggesting that it is well suited to living in the gut
      (and possibly the circulatory system) of its mosquito hosts. In comparison, S.
      taiwanense has lost several carbohydrate utilization genes and acquired
      additional sets of oligopeptide transporter genes through tandem duplications,
      suggesting that proteins from digested blood meal or lysed host cells may be an
      important nutrient source. Moreover, one glycerol-3-phosphate oxidase gene (glpO)
      was found in S. taiwanense but not S. diminutum. This gene is linked to the
      production of reactive oxygen species and has been shown to be a major virulence
      factor in Mycoplasma mycoides. This finding may explain the pathogenicity of S.
      taiwanense observed in previous artificial infection experiments, while no
      apparent effect was found for S. diminutum. To infer the gene content evolution
      at deeper divergence levels, we incorporated other Mollicutes genomes for
      comparative analyses. The results suggest that the losses of biosynthetic
      pathways are a recurrent theme in these host-associated bacteria. 

PMID- 23873927
TI  - Pollen and plant reproduction biology: blooming from East to West.

PMID- 23873928
TI  - Signaling in pollen tube growth: crosstalk, feedback, and missing links.
AB  - Pollen tubes elongate rapidly at their tips through highly polarized cell growth
      known as tip growth. Tip growth requires intensive exocytosis at the tip, which
      is supported by a dynamic cytoskeleton and vesicle trafficking. Several signaling
      pathways have been demonstrated to coordinate pollen tube growth by regulating
      cellular activities such as actin dynamics, exocytosis, and endocytosis. These
      signaling pathways crosstalk to form a signaling network that coordinates the
      cellular processes required for tip growth. The homeostasis of key signaling
      molecules is critical for the proper elongation of the pollen tube tip, and is
      commonly fine-tuned by positive and negative regulations. In addition to the
      major signaling pathways, emerging evidence implies the roles of other signals in
      the regulation of pollen tube growth. Here we review and discuss how these
      signaling networks modulate the rapid growth of pollen tubes. 

PMID- 23873929
TI  - Silkworm apolipophorin protein inhibits hemolysin gene expression of
      Staphylococcus aureus via binding to cell surface lipoteichoic acids.
AB  - We previously reported that a silkworm hemolymph protein, apolipophorin (ApoLp),
      binds to the cell surface of Staphylococcus aureus and inhibits expression of the
      saePQRS operon encoding a two-component system, SaeRS, and hemolysin genes. In
      this study, we investigated the inhibitory mechanism of ApoLp on S. aureus
      hemolysin gene expression. ApoLp bound to lipoteichoic acids (LTA), an S. aureus
      cell surface component. The addition of purified LTA to liquid medium abolished
      the inhibitory effect of ApoLp against S. aureus hemolysin production. In an S.
      aureus knockdown mutant of ltaS encoding LTA synthetase, the inhibitory effects
      of ApoLp on saeQ expression and hemolysin production were attenuated.
      Furthermore, the addition of anti-LTA monoclonal antibody to liquid medium
      decreased the expression of S. aureus saeQ and hemolysin genes. In S. aureus
      strains expressing SaeS mutant proteins with a shortened extracellular domain,
      ApoLp did not decrease saeQ expression. These findings suggest that ApoLp binds
      to LTA on the S. aureus cell surface and inhibits S. aureus hemolysin gene
      expression via a two-component regulatory system, SaeRS. 

PMID- 23873930
TI  - Cellular localization and characterization of cytosolic binding partners for Gla
      domain-containing proteins PRRG4 and PRRG2.
AB  - The genes encoding a family of proteins termed proline-rich gamma-carboxyglutamic
      acid (PRRG) proteins were identified and characterized more than a decade ago,
      but their functions remain unknown. These novel membrane proteins have an
      extracellular gamma-carboxyglutamic acid (Gla) protein domain and cytosolic WW
      binding motifs. We screened WW domain arrays for cytosolic binding partners for
      PRRG4 and identified novel protein-protein interactions for the protein. We also
      uncovered a new WW binding motif in PRRG4 that is essential for these newly found
      protein-protein interactions. Several of the PRRG-interacting proteins we
      identified are essential for a variety of physiologic processes. Our findings
      indicate possible novel and previously unidentified functions for PRRG proteins. 

PMID- 23873931
TI  - Src family protein tyrosine kinase regulates the basolateral K channel in the
      distal convoluted tubule (DCT) by phosphorylation of KCNJ10 protein.
AB  - The loss of function of the basolateral K channels in the distal nephron causes
      electrolyte imbalance. The aim of this study is to examine the role of Src family
      protein tyrosine kinase (SFK) in regulating K channels in the basolateral
      membrane of the mouse initial distal convoluted tubule (DCT1). Single-channel
      recordings confirmed that the 40-picosiemen (pS) K channel was the only type of K
      channel in the basolateral membrane of DCT1. The suppression of SFK reversibly
      inhibited the basolateral 40-pS K channel activity in cell-attached patches and
      decreased the Ba(2+)-sensitive whole-cell K currents in DCT1. Inhibition of SFK
      also shifted the K reversal potential from -65 to -43 mV, suggesting a role of
      SFK in determining the membrane potential in DCT1. Western blot analysis showed
      that KCNJ10 (Kir4.1), a key component of the basolateral 40-pS K channel in DCT1,
      was a tyrosine-phosphorylated protein. LC/MS analysis further confirmed that SFK
      phosphorylated KCNJ10 at Tyr(8) and Tyr(9). The single-channel recording detected
      the activity of a 19-pS K channel in KCNJ10-transfected HEK293T cells and a 40-pS
      K channel in the cells transfected with KCNJ10+KCNJ16 (Kir.5.1) that form a
      heterotetramer in the basolateral membrane of the DCT. Mutation of Tyr(9) did not
      alter the channel conductance of the homotetramer and heterotetramer. However, it
      decreased the whole-cell K currents, the probability of finding K channels, and
      surface expression of KCNJ10 in comparison to WT KCNJ10. We conclude that SFK
      stimulates the basolateral K channel activity in DCT1, at least partially, by
      phosphorylating Tyr(9) on KCNJ10. We speculate that the modulation of tyrosine
      phosphorylation of KCNJ10 should play a role in regulating membrane transport
      function in DCT1. 

PMID- 23873932
TI  - Nuclear factor kappaB2 p52 protein has a role in antiviral immunity through
      IkappaB kinase epsilon-dependent induction of Sp1 protein and interleukin 15.
AB  - In this study we describe a previously unreported function for NFkappaB2, an
      NFkappaB family transcription factor, in antiviral immunity. NFkappaB2 is induced
      in response to poly(I:C), a mimic of viral dsRNA. Poly(I:C), acting via TLR3,
      induces p52-dependent transactivation of a reporter gene in a manner that
      requires the kinase activity of IkappaB kinase epsilon (IKKepsilon) and the
      transactivating potential of RelA/p65. We identify a novel NFkappaB2 binding site
      in the promoter of the transcription factor Sp1 that is required for Sp1 gene
      transcription activated by poly(I:C). We show that Sp1 is required for IL-15
      induction by both poly(I:C) and respiratory syncytial virus, a response that also
      requires NFkappaB2 and IKKepsilon. Our study identifies NFkappaB2 as a target for
      IKKepsilon in antiviral immunity and describes, for the first time, a role for
      NFkappaB2 in the regulation of gene expression in response to viral infection. 

PMID- 23873934
TI  - Modulation of human mitochondrial voltage-dependent anion channel 2 (hVDAC-2)
      structural stability by cysteine-assisted barrel-lipid interactions.
AB  - Human mitochondrial voltage-dependent anion channel 2 (hVDAC-2), the most
      predominant isoform seen in brain mitochondria, is not only crucial for cell
      survival but is also implicated in Alzheimer disease. The abundance of cysteines
      in this isoform is particularly fascinating, as hVDAC-1 cysteines have no
      associated functional role. We report a detailed biophysical examination of a Cys
      less mutant of hVDAC-2, and its behavioral comparison with the wild type protein.
      Our findings suggest that cysteine mutation results in the formation of a better
      barrel at the expense of weakened protein-lipid interactions. The wild type
      protein displays stronger lipid association, despite being less structured. A
      reversal in behavior of both proteins is observed in the case of chemical
      denaturation, with the Cys-less mutant exhibiting lowered unfolding free
      energies. In bicellar systems comprising 14-C phosphocholines, we observe that
      protein-lipid interactions are weakened in both constructs, resulting in barrel
      structure destabilization. Our biochemical and biophysical studies together
      reveal key structural roles for the cysteine residues. We find that minor
      conformational variations in local residues are sufficient to define the membrane
      protein dynamics in hVDAC-2. Such subtle sequence variations contribute to
      differential stability of VDACs and may have implications in their in vivo
      regulation and recycling. 

PMID- 23873933
TI  - Identification of C-terminal phosphorylation sites of N-formyl peptide receptor-1
      (FPR1) in human blood neutrophils.
AB  - Accumulation, activation, and control of neutrophils at inflammation sites is
      partly driven by N-formyl peptide chemoattractant receptors (FPRs). Occupancy of
      these G-protein-coupled receptors by formyl peptides has been shown to induce
      regulatory phosphorylation of cytoplasmic serine/threonine amino acid residues in
      heterologously expressed recombinant receptors, but the biochemistry of these
      modifications in primary human neutrophils remains relatively unstudied. FPR1 and
      FPR2 were partially immunopurified using antibodies that recognize both receptors
      (NFPRa) or unphosphorylated FPR1 (NFPRb) in dodecylmaltoside extracts of
      unstimulated and N-formyl-Met-Leu-Phe (fMLF) + cytochalasin B-stimulated
      neutrophils or their membrane fractions. After deglycosylation and separation by
      SDS-PAGE, excised Coomassie Blue-staining bands (~34,000 Mr) were tryptically
      digested, and FPR1, phospho-FPR1, and FPR2 content was confirmed by peptide mass
      spectrometry. C-terminal FPR1 peptides (Leu(312)-Arg(322) and Arg(323)-Lys(350))
      and extracellular FPR1 peptide (Ile(191)-Arg(201)) as well as three similarly
      placed FPR2 peptides were identified in unstimulated and fMLF + cytochalasin B
      stimulated samples. LC/MS/MS identified seven isoforms of Ala(323)-Lys(350) only
      in the fMLF + cytochalasin B-stimulated sample. These were individually
      phosphorylated at Thr(325), Ser(328), Thr(329), Thr(331), Ser(332), Thr(334), and
      Thr(339). No phospho-FPR2 peptides were detected. Cytochalasin B treatment of
      neutrophils decreased the sensitivity of fMLF-dependent NFPRb recognition 2-fold,
      from EC50 = 33 +/- 8 to 74 +/- 21 nM. Our results suggest that 1) partial
      immunopurification, deglycosylation, and SDS-PAGE separation of FPRs is
      sufficient to identify C-terminal FPR1 Ser/Thr phosphorylations by LC/MS/MS; 2)
      kinases/phosphatases activated in fMLF/cytochalasin B-stimulated neutrophils
      produce multiple C-terminal tail FPR1 Ser/Thr phosphorylations but have little
      effect on corresponding FPR2 sites; and 3) the extent of FPR1 phosphorylation can
      be monitored with C-terminal tail FPR1-phosphospecific antibodies.

PMID- 23873935
TI  - A pre-microRNA-149 (miR-149) genetic variation affects miR-149 maturation and its
      ability to regulate the Puma protein in apoptosis.
AB  - MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that function as
      negative regulators of gene expression. They are transcribed from endogenous DNA
      and form hairpin structures (termed as pre-miRNAs) that are processed to form
      mature miRNAs. It remains largely unknown as to the molecular consequences of the
      natural genetic variation in pre-miRNAs. Here, we report that an A->G
      polymorphism (rs71428439) is located in Homo sapiens miR-149 stem-loop region.
      This polymorphism results in a change in the structure of the miR-149 precursor.
      Our results showed that the genotype distribution of this polymorphism in
      myocardial infarction cases was significantly different from that in the control
      subjects. We examined the biological significance of this polymorphism on the
      production of mature miR-149, and we observed that the G-allelic miR-149
      precursor displayed a lower production of mature miR-149 compared with the A
      allelic one. Further investigations disclosed that miR-149 could withstand
      mitochondrial fission and apoptosis through targeting the pro-apoptotic factor
      p53-up-regulated modulator of apoptosis (Puma). Enforced expression of miR-149
      promoted cell survival, whereas knockdown of miR-149 rendered cells to be
      sensitive to apoptotic stimulation. Intriguingly, the A to G variation led pre
      miR-149 to elicit an attenuated effect on the inhibition of mitochondrial fission
      and apoptosis. Finally, this polymorphism exerts its influence on cardiac
      function in the mouse model of myocardial infarction. These data suggest that
      this polymorphism in the miR-149 precursor may result in important phenotypic
      traits of myocardial infarction. Our findings warrant further investigations on
      the relationship between miR-149 polymorphism and myocardial infarction. 

PMID- 23873936
TI  - Physical and functional association of lactate dehydrogenase (LDH) with skeletal
      muscle mitochondria.
AB  - The intracellular lactate shuttle hypothesis posits that lactate generated in the
      cytosol is oxidized by mitochondrial lactate dehydrogenase (LDH) of the same
      cell. To examine whether skeletal muscle mitochondria oxidize lactate,
      mitochondrial respiratory oxygen flux (JO2) was measured during the sequential
      addition of various substrates and cofactors onto permeabilized rat gastrocnemius
      muscle fibers, as well as isolated mitochondrial subpopulations. Addition of
      lactate did not alter JO2. However, subsequent addition of NAD(+) significantly
      increased JO2, and was abolished by the inhibitor of mitochondrial pyruvate
      transport, alpha-cyano-4-hydroxycinnamate. In experiments with isolated
      subsarcolemmal and intermyofibrillar mitochondrial subpopulations, only
      subsarcolemmal exhibited NAD(+)-dependent lactate oxidation. To further
      investigate the details of the physical association of LDH with mitochondria in
      muscle, immunofluorescence/confocal microscopy and immunoblotting approaches were
      used. LDH clearly colocalized with mitochondria in intact, as well as
      permeabilized fibers. LDH is likely localized inside the outer mitochondrial
      membrane, but not in the mitochondrial matrix. Collectively, these results
      suggest that extra-matrix LDH is strategically positioned within skeletal muscle
      fibers to functionally interact with mitochondria. 

PMID- 23873938
TI  - Subnuclear partitioning of rRNA genes between the nucleolus and nucleoplasm
      reflects alternative epiallelic states.
AB  - Eukaryotes can have thousands of 45S ribosomal RNA (rRNA) genes, many of which
      are silenced during development. Using fluorescence-activated sorting techniques,
      we show that active rRNA genes in Arabidopsis thaliana are present within sorted
      nucleoli, whereas silenced rRNA genes are excluded. DNA methyltransferase (met1),
      histone deacetylase (hda6), or chromatin assembly (caf1) mutants that disrupt
      silencing abrogate this nucleoplasmic-nucleolar partitioning. Bisulfite
      sequencing data indicate that active nucleolar rRNA genes are nearly completely
      demethylated at promoter CGs, whereas silenced genes are nearly fully methylated.
      Collectively, the data reveal that rRNA genes occupy distinct but changeable
      nuclear territories according to their epigenetic state. 

PMID- 23873937
TI  - Does the microenvironment influence the cell types of origin for prostate cancer?
AB  - Despite several recent studies addressing the cells of origin for prostate
      cancer, there is still considerable discussion in the field regarding the most
      relevant target populations for transformation. Tissue regeneration studies have
      pointed to a basal cell origin for mouse and human prostate cancer. In contrast,
      genetically engineered mouse models demonstrate that cells within both the basal
      and luminal layers can initiate murine prostate cancer. Based on differences
      between these two approaches, we propose that further work should address the
      requirement for microenvironmental components such as immune or mesenchymal cells
      on epithelial cell types of origin for prostate cancer. 

PMID- 23873939
TI  - The CLAMP protein links the MSL complex to the X chromosome during Drosophila
      dosage compensation.
AB  - The Drosophila male-specific lethal (MSL) dosage compensation complex increases
      transcript levels on the single male X chromosome to equal the transcript levels
      in XX females. However, it is not known how the MSL complex is linked to its DNA
      recognition elements, the critical first step in dosage compensation. Here, we
      demonstrate that a previously uncharacterized zinc finger protein, CLAMP
      (chromatin-linked adaptor for MSL proteins), functions as the first link between
      the MSL complex and the X chromosome. CLAMP directly binds to the MSL complex DNA
      recognition elements and is required for the recruitment of the MSL complex. The
      discovery of CLAMP identifies a key factor required for the chromosome-specific
      targeting of dosage compensation, providing new insights into how subnuclear
      domains of coordinate gene regulation are formed within metazoan genomes. 

PMID- 23873940
TI  - Differential Tks5 isoform expression contributes to metastatic invasion of lung
      adenocarcinoma.
AB  - Metastasis accounts for the vast majority of cancer-related deaths, yet the
      molecular mechanisms that drive metastatic spread remain poorly understood. Here
      we report that Tks5, which has been linked to the formation of proteolytic
      cellular protrusions known as invadopodia, undergoes an isoform switch during
      metastatic progression in a genetically engineered mouse model of lung
      adenocarcinoma. Nonmetastatic primary tumor-derived cells predominantly expressed
      a short isoform, Tks5short, while metastatic primary tumor- and metastasis
      derived cells acquired increased expression of the full-length isoform Tks5long.
      This elevation of Tks5long to Tks5short ratio correlated with a commensurate
      increase in invadopodia activity in metastatic cells compared with nonmetastatic
      cells. Further characterization of these isoforms by knockdown and overexpression
      experiments demonstrated that Tks5long promoted invadopodia in vitro and
      increased metastasis in transplant models and an autochthonous model of lung
      adenocarcinoma. Conversely, Tks5short decreased invadopodia stability and
      proteolysis, acting as a natural dominant-negative inhibitor to Tks5long.
      Importantly, high Tks5long and low Tks5short expressions in human lung
      adenocarcinomas correlated with metastatic disease and predicted worse survival
      of early stage patients. These data indicate that tipping the Tks5 isoform
      balance to a high Tks5long to Tks5short ratio promotes invadopodia-mediated
      invasion and metastasis. 

PMID- 23873941
TI  - Spatially distinct roles of class Ia PI3K isoforms in the development and
      maintenance of PTEN hamartoma tumor syndrome.
AB  - PTEN hamartoma tumor syndrome (PHTS) comprises a collection of genetic disorders
      associated with germline mutations in the tumor suppressor gene PTEN. Therapeutic
      options and preventative measures for PHTS are limited. Using both genetically
      engineered mouse models and pharmacological PI3K isoform-selective inhibitors, we
      found that the roles of PI3K isoforms are spatially distinct in the skin: While
      p110alpha is responsible for the sustained survival of suprabasal cells of the
      epidermis in the absence of PTEN, p110beta is important for the
      hyperproliferation of basal cells in PHTS. Furthermore, we identified a
      differential expression pattern of p110alpha and p110beta in basal and suprabasal
      keratinocytes as well as differential PI3K regulation by upstream signals in the
      basal and suprabasal compartments of the epidermis, providing a potential
      molecular mechanism underlying the specific roles of PI3K isoforms in the
      epidermis. Finally, we demonstrate that combined inhibition of both PI3K isoforms
      prevents the development of PHTS and also reverses skin hamartomas that have
      reached advanced stages in mice. Together, these results not only advance our
      overall understanding of the diverse roles of PI3K isoforms, but also have the
      potential for meaningful translation via the clinical utilization of PI3K
      inhibitors for both prevention and therapy in PHTS patients. 

PMID- 23873942
TI  - A TAF4 coactivator function for E proteins that involves enhanced TFIID binding.
AB  - The multisubunit TFIID plays a direct role in transcription initiation by binding
      to core promoter elements and directing preinitiation complex assembly. Although
      TFIID may also function as a coactivator through direct interactions with
      promoter-bound activators, mechanistic aspects of this poorly defined function
      remain unclear. Here, biochemical studies show a direct TFIID-E-protein
      interaction that (1) is mediated through interaction of a novel E-protein
      activation domain (activation domain 3 [AD3]) with the TAF homology (TAFH) domain
      of TAF4, (2) is critical for activation of a natural target gene by an E protein,
      and (3) mechanistically acts by enhancing TFIID binding to the core promoter.
      Complementary assays establish a gene-specific role for the TAFH domain in TFIID
      recruitment and activation of a large subset of genes in vivo. These results
      firmly establish TAF4 as a bona fide E-protein coactivator as well as a mechanism
      involving facilitated TFIID binding through direct interaction with an E-protein
      activation domain. 

PMID- 23873943
TI  - ATR phosphorylates SMARCAL1 to prevent replication fork collapse.
AB  - The DNA damage response kinase ataxia telangiectasia and Rad3-related (ATR)
      coordinates much of the cellular response to replication stress. The exact
      mechanisms by which ATR regulates DNA synthesis in conditions of replication
      stress are largely unknown, but this activity is critical for the viability and
      proliferation of cancer cells, making ATR a potential therapeutic target. Here we
      use selective ATR inhibitors to demonstrate that acute inhibition of ATR kinase
      activity yields rapid cell lethality, disrupts the timing of replication
      initiation, slows replication elongation, and induces fork collapse. We define
      the mechanism of this fork collapse, which includes SLX4-dependent cleavage
      yielding double-strand breaks and CtIP-dependent resection generating excess
      single-stranded template and nascent DNA strands. Our data suggest that the DNA
      substrates of these nucleases are generated at least in part by the SMARCAL1 DNA
      translocase. Properly regulated SMARCAL1 promotes stalled fork repair and
      restart; however, unregulated SMARCAL1 contributes to fork collapse when ATR is
      inactivated in both mammalian and Xenopus systems. ATR phosphorylates SMARCAL1 on
      S652, thereby limiting its fork regression activities and preventing aberrant
      fork processing. Thus, phosphorylation of SMARCAL1 is one mechanism by which ATR
      prevents fork collapse, promotes the completion of DNA replication, and maintains
      genome integrity. 

PMID- 23873946
TI  - Umbilical hernia.

PMID- 23873945
TI  - Death, debility, and destitution following hip fracture.
AB  - BACKGROUND: We examined the effects of hip fracture on mortality, entry into long
      term institutional care, and new evidence of poverty. We estimate of the
      proportion of hip fracture patients who require not just short-term
      rehabilitation but who become dependent on long-term institutional care, and the
      risk of becoming newly dependent on Medicaid or eligible for low-income subsidies
      following hip fracture. METHODS: We used data from 2005 through 2010 for a random
      5% sample of Medicare beneficiaries (N = 3.1 million) to conduct a retrospective
      matched cohort study. We used high-dimensional propensity score matching to
      compare outcomes for patients who experienced a hip fracture with subjects who
      did not, but had similar propensity for suffering a hip fracture. We then
      compared the 1-year risk of death, debility, and destitution between groups.
      RESULTS: We matched 43,210 hip fracture patients to comparators without a hip
      fracture. Hip fractures were associated with more than a twofold increase in
      likelihood of mortality (incidence proportion ratio [IPR] of 2.27, 95% CI, 2.20
      2.34), a fourfold increase in likelihood of requiring long-term nursing facility
      care (IPR, 3.96; 95% CI, 3.77-4.16), and a twofold increase in the probability of
      entering into low-income status (IPR, 2.14; 95% CI 1.99-2.31) within 1 year
      following hip fracture compared with subjects without a hip fracture.
      CONCLUSIONS: Hip fracture in elderly patients resulted in increased death,
      debility, and destitution. Initiatives that lead to improved treatment of
      osteoporosis could result in a decrease in incidence of fractures, subsequent
      death, debility, and destitution for older adults.

PMID- 23873948
TI  - Outcomes incentives: can they catch on in the US?

PMID- 23873949
TI  - Accountable care organization program cuts costs and improves care, report says.

PMID- 23873947
TI  - Overlapping meta-analyses on the same topic: survey of published studies.
AB  - OBJECTIVE: To assess how common it is to have multiple overlapping meta-analyses
      of randomized trials published on the same topic. DESIGN: Survey of published
      meta-analyses. DATA SOURCES: PubMed. STUDY SELECTION AND METHODS: Meta-analyses
      published in 2010 were identified, and 5% of them were randomly selected. We
      further selected those that included randomized trials and examined effectiveness
      of any medical intervention. For eligible meta-analyses, we searched for other
      meta-analyses on the same topic (covering the same comparisons,
      indications/settings, and outcomes or overlapping subsets of them) published
      until February 2013. RESULTS: Of 73 eligible meta-analyses published in 2010, 49
      (67%) had at least one other overlapping meta-analysis (median two meta-analyses
      per topic, interquartile range 1-4, maximum 13). In 17 topics at least one author
      was involved in at least two of the overlapping meta-analyses. No characteristics
      of the index meta-analyses were associated with the potential for overlapping
      meta-analyses. Among pairs of overlapping meta-analyses in 20 randomly selected
      topics, 13 of the more recent meta-analyses did not include any additional
      outcomes. In three of the four topics with eight or more published meta-analyses,
      many meta-analyses examined only a subset of the eligible interventions or
      indications/settings covered by the index meta-analysis. Conversely, for statins
      in the prevention of atrial fibrillation after cardiac surgery, 11 meta-analyses
      were published with similar eligibility criteria for interventions and setting:
      there was still variability on which studies were included, but the results were
      always similar or even identical across meta-analyses. CONCLUSIONS: While some
      independent replication of meta-analyses by different teams is possibly useful,
      the overall picture suggests that there is a waste of efforts with many topics
      covered by multiple overlapping meta-analyses.

PMID- 23873950
TI  - Study maps the link between socioeconomic status and tobacco use across India.

PMID- 23873951
TI  - Government launches consultation on how to deliver cap on social care costs.

PMID- 23873952
TI  - Systematic review finds no benefits to population screening for dementia.

PMID- 23873953
TI  - HFEA and HTA will remain as separate bodies but will pool some support services.

PMID- 23873954
TI  - A comprehensive gene regulatory network for the diauxic shift in Saccharomyces
      cerevisiae.
AB  - Existing machine-readable resources for large-scale gene regulatory networks
      usually do not provide context information characterizing the activating
      conditions for a regulation and how targeted genes are affected. Although this
      information is essentially required for data interpretation, available networks
      are often restricted to not condition-dependent, non-quantitative, plain binary
      interactions as derived from high-throughput screens. In this article, we present
      a comprehensive Petri net based regulatory network that controls the diauxic
      shift in Saccharomyces cerevisiae. For 100 specific enzymatic genes, we collected
      regulations from public databases as well as identified and manually curated >400
      relevant scientific articles. The resulting network consists of >300 multi-input
      regulatory interactions providing (i) activating conditions for the regulators;
      (ii) semi-quantitative effects on their targets; and (iii) classification of the
      experimental evidence. The diauxic shift network compiles widespread distributed
      regulatory information and is available in an easy-to-use machine-readable form.
      Additionally, we developed a browsable system organizing the network into pathway
      maps, which allows to inspect and trace the evidence for each annotated
      regulation in the model. 

PMID- 23873955
TI  - Arpeggio: harmonic compression of ChIP-seq data reveals protein-chromatin
      interaction signatures.
AB  - Researchers generating new genome-wide data in an exploratory sequencing study
      can gain biological insights by comparing their data with well-annotated data
      sets possessing similar genomic patterns. Data compression techniques are needed
      for efficient comparisons of a new genomic experiment with large repositories of
      publicly available profiles. Furthermore, data representations that allow
      comparisons of genomic signals from different platforms and across species
      enhance our ability to leverage these large repositories. Here, we present a
      signal processing approach that characterizes protein-chromatin interaction
      patterns at length scales of several kilobases. This allows us to efficiently
      compare numerous chromatin-immunoprecipitation sequencing (ChIP-seq) data sets
      consisting of many types of DNA-binding proteins collected from a variety of
      cells, conditions and organisms. Importantly, these interaction patterns broadly
      reflect the biological properties of the binding events. To generate these
      profiles, termed Arpeggio profiles, we applied harmonic deconvolution techniques
      to the autocorrelation profiles of the ChIP-seq signals. We used 806 publicly
      available ChIP-seq experiments and showed that Arpeggio profiles with similar
      spectral densities shared biological properties. Arpeggio profiles of ChIP-seq
      data sets revealed characteristics that are not easily detected by standard peak
      finders. They also allowed us to relate sequencing data sets from different
      genomes, experimental platforms and protocols. Arpeggio is freely available at
      http://sourceforge.net/p/arpeggio/wiki/Home/. 

PMID- 23873956
TI  - Conformational changes of the phenyl and naphthyl isocyanate-DNA adducts during
      DNA replication and by minor groove binding molecules.
AB  - DNA lesions produced by aromatic isocyanates have an extra bulky group on the
      nucleotide bases, with the capability of forming stacking interaction within a
      DNA helix. In this work, we investigated the conformation of the 2'
      deoxyadenosine and 2'-deoxycytidine derivatives tethering a phenyl or naphthyl
      group, introduced in a DNA duplex. The chemical modification experiments using
      KMnO4 and 1-cyclohexyl-3 -(2-morpholinoethyl) carbodiimide metho-p
      toluenesulfonate have shown that the 2'-deoxycytidine lesions form the base pair
      with guanine while the 2'-deoxyadenosine lesions have less ability of forming the
      base pair with thymine in solution. Nevertheless, the kinetic analysis shows that
      these DNA lesions are compatible with DNA ligase and DNA polymerase reactions, as
      much as natural DNA bases. We suggest that the adduct lesions have a capability
      of adopting dual conformations, depending on the difference in their interaction
      energies between stacking of the attached aromatic group and base pairing through
      hydrogen bonds. It is also presented that the attached aromatic groups change
      their orientation by interacting with the minor groove binding netropsin,
      distamycin and synthetic polyamide. The nucleotide derivatives would be useful
      for enhancing the phenotypic diversity of DNA molecules and for exploring new non
      natural nucleotides. 

PMID- 23873957
TI  - Minimal genome encoding proteins with constrained amino acid repertoire.
AB  - Minimal bacterial gene set comprises the genetic elements needed for survival of
      engineered bacterium on a rich medium. This set is estimated to include 300-350
      protein-coding genes. One way of simplifying an organism with such a minimal
      genome even further is to constrain the amino acid content of its proteins. In
      this study, comparative genomics approaches and the results of gene knockout
      experiments were used to extrapolate the minimal gene set of mollicutes, and
      bioinformatics combined with the knowledge-based analysis of the structure
      function relationships in these proteins and their orthologs, paralogs and
      analogs was applied to examine the challenges of completely replacing the rarest
      residue, cysteine. Among several known functions of cysteine residues, their
      roles in the active centers of the enzymes responsible for deoxyribonucleoside
      synthesis and transfer RNA modification appear to be crucial, as no alternative
      chemistry is known for these reactions. Thus, drastic reduction of the content of
      the rarest amino acid in a minimal proteome appears to be possible, but its
      complete elimination is challenging. 

PMID- 23873958
TI  - HCV IRES interacts with the 18S rRNA to activate the 40S ribosome for subsequent
      steps of translation initiation.
AB  - Previous analyses of complexes of 40S ribosomal subunits with the hepatitis C
      virus (HCV) internal ribosome entry site (IRES) have revealed contacts made by
      the IRES with ribosomal proteins. Here, using chemical probing, we show that the
      HCV IRES also contacts the backbone and bases of the CCC triplet in the 18S
      ribosomal RNA (rRNA) expansion segment 7. These contacts presumably provide
      interplay between IRES domain II and the AUG codon close to ribosomal protein S5,
      which causes a rearrangement of 18S rRNA structure in the vicinity of the
      universally conserved nucleotide G1639. As a result, G1639 becomes exposed and
      the corresponding site of the 40S subunit implicated in transfer RNA
      discrimination can select . These data are the first demonstration at nucleotide
      resolution of direct IRES-rRNA interactions and how they induce conformational
      transition in the 40S subunit allowing the HCV IRES to function without AUG
      recognition initiation factors. 

PMID- 23873959
TI  - Single molecule quantitation and sequencing of rare translocations using
      microfluidic nested digital PCR.
AB  - Cancers are heterogeneous and genetically unstable. New methods are needed that
      provide the sensitivity and specificity to query single cells at the genetic loci
      that drive cancer progression, thereby enabling researchers to study the
      progression of individual tumors. Here, we report the development and application
      of a bead-based hemi-nested microfluidic droplet digital PCR (dPCR) technology to
      achieve 'quantitative' measurement and single-molecule sequencing of somatically
      acquired carcinogenic translocations at extremely low levels (<10(-6)) in healthy
      subjects. We use this technique in our healthy study population to determine the
      overall concentration of the t(14;18) translocation, which is strongly associated
      with follicular lymphoma. The nested dPCR approach improves the detection limit
      to 1*10(-7) or lower while maintaining the analysis efficiency and specificity.
      Further, the bead-based dPCR enabled us to isolate and quantify the relative
      amounts of the various clonal forms of t(14;18) translocation in these subjects,
      and the single-molecule sensitivity and resolution of dPCR led to the discovery
      of new clonal forms of t(14;18) that were otherwise masked by the conventional
      quantitative PCR measurements. In this manner, we created a quantitative map for
      this carcinogenic mutation in this healthy population and identified the
      positions on chromosomes 14 and 18 where the vast majority of these t(14;18)
      events occur.

PMID- 23873961
TI  - Americans are already benefiting from health reform, says Obama.

PMID- 23873960
TI  - DBSI: DNA-binding site identifier.
AB  - In this study, we present the DNA-Binding Site Identifier (DBSI), a new structure
      based method for predicting protein interaction sites for DNA binding. DBSI was
      trained and validated on a data set of 263 proteins (TRAIN-263), tested on an
      independent set of protein-DNA complexes (TEST-206) and data sets of 29 unbound
      (APO-29) and 30 bound (HOLO-30) protein structures distinct from the training
      data. We computed 480 candidate features for identifying protein residues that
      bind DNA, including new features that capture the electrostatic microenvironment
      within shells near the protein surface. Our iterative feature selection process
      identified features important in other models, as well as features unique to the
      DBSI model, such as a banded electrostatic feature with spatial separation
      comparable with the canonical width of the DNA minor groove. Validations and
      comparisons with established methods using a range of performance metrics clearly
      demonstrate the predictive advantage of DBSI, and its comparable performance on
      unbound (APO-29) and bound (HOLO-30) conformations demonstrates robustness to
      binding-induced protein conformational changes. Finally, we offer our feature
      data table to others for integration into their own models or for testing
      improved feature selection and model training strategies based on DBSI. 

PMID- 23873962
TI  - Impaired systolic blood pressure recovery directly after standing predicts
      mortality in older falls clinic patients.
AB  - BACKGROUND: Normally, standing up causes a blood pressure (BP) drop within 15
      seconds, followed by recovery to baseline driven by BP control mechanisms. The
      prognostic value of this initial BP drop, but also of the recovery hereafter, is
      unknown. The aim of this study was to examine the prognostic value of these BP
      characteristics in response to standing. METHODS: In a retrospective cohort study
      of 238 consecutive patients visiting our falls outpatient clinic, we examined the
      relation between all-cause mortality and BP decline and recovery directly after
      active standing up with Cox proportional hazards analyses. RESULTS: Of 238
      patients (mean age 78.4 +/- 7.8 years), during a median follow-up of 21.0 months,
      36 (15%) patients died. Neither absolute nor relative (%) initial BP drop after
      standing predicted mortality. In contrast, the magnitude of BP recovery 40-60
      seconds after standing was associated with mortality, even after adjustment for
      age, comorbidity, and other baseline characteristics. When systolic BP had
      recovered to less than 80% of prestanding baseline after 60 seconds of standing,
      this was a powerful independent predictor of mortality (hazard ratio: 3.00; 95%
      confidence interval 1.17-7.68). CONCLUSIONS: Failure to recover from BP decline
      in the first minute after active standing up is associated with excess mortality
      in falls clinic patients. A recovery of systolic BP to less than 80% of baseline
      after 60 seconds may be used as an easily available cardiovascular marker for
      increased mortality risk in older falls clinic patients.

PMID- 23873963
TI  - Mice producing reduced levels of insulin-like growth factor type 1 display an
      increase in maximum, but not mean, life span.
AB  - Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in
      multiple invertebrate organisms. Studies on mammalian longevity suggest that
      reducing levels of IGF-1 may also increase life span. However, the data are
      conflicting and complicated by the physiology of the mammalian neuroendocrine
      system. We have performed life-span analysis on mice homozygous for an insertion
      in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a
      phenotype consistent with a significant decrease in IGF-1. Life-span analysis was
      carried out at three independent locations. Although the life-span data varied
      between sites, the maximum life span of the IGF-1-deficient mice was
      significantly increased and age-specific mortality rates were reduced in the IGF
      1-deficient mice; however, mean life span did not differ except at one site,
      where mean life span was increased in female IGF-1-deficient animals. Early life
      mortality was noted in one cohort of IGF-1-deficient mice. The results are
      consistent with a significant role for IGF-1 in the modulation of life span but
      contrast with the published life-span data for the hypopituitary Ames and Snell
      dwarf mice and growth hormone receptor null mice, indicating that a reduction in
      IGF-1 alone is insufficient to increase both mean and maximal life span in mice. 

PMID- 23873964
TI  - Age-associated remodeling of the intestinal epithelial barrier.
AB  - Disorders of the gastrointestinal tract are common in the elderly people;
      however, the precise trait(s) of aging that contribute to the vulnerability of
      the gastrointestinal tract are poorly understood. Recent evidence suggests that
      patients with gastrointestinal disorders have increased intestinal permeability.
      Here, we address the hypothesis that disruption of the intestinal barrier is
      associated with aging. Our results demonstrated that permeability was
      significantly higher in colonic biopsies collected from old baboons compared with
      young baboons. Additionally, colonic tissue from the older animals had decreased
      zonula occluden-1, occludin, and junctional adhesion molecule-A tight junction
      protein expression and increased claudin-2 expression. Upregulation of miR-29a
      and inflammatory cytokines IFN-gamma, IL-6, and IL-1beta was also found in
      colonic biopsies from old baboons relative to young baboons. These results show
      for the first time that a pivotal contributing factor to geriatric vulnerability
      to gastrointestinal dysfunction may be increased colonic permeability via age
      associated remodeling of intestinal epithelial tight junction proteins. 

PMID- 23873965
TI  - Markers of human skeletal muscle mitochondrial biogenesis and quality control:
      effects of age and aerobic exercise training.
AB  - Perturbations in mitochondrial health may foster age-related losses of aerobic
      capacity (VO2peak) and skeletal muscle size. However, limited data exist
      regarding mitochondrial dynamics in aging human skeletal muscle and the influence
      of exercise. The purpose of this study was to examine proteins regulating
      mitochondrial biogenesis and dynamics, VO2peak, and skeletal muscle size before
      and after aerobic exercise training in young men (20 +/- 1 y) and older men (74
      +/- 3 y). Exercise-induced skeletal muscle hypertrophy occurred independent of
      age, whereas the improvement in VO2peak was more pronounced in young men. Aerobic
      exercise training increased proteins involved with mitochondrial biogenesis,
      fusion, and fission, independent of age. This is the first study to examine
      pathways of mitochondrial quality control in aging human skeletal muscle with
      aerobic exercise training. These data indicate normal aging does not influence
      proteins associated with mitochondrial health or the ability to respond to
      aerobic exercise training at the mitochondrial and skeletal muscle levels. 

PMID- 23873967
TI  - Concordance of physical activity trajectories among middle-aged and older married
      couples: impact of diseases and functional difficulties.
AB  - OBJECTIVES: This study examined spousal concordance of physical activity
      trajectories among middle-aged and older married couples and the influences of
      recent diseases and functional difficulties on individuals' trajectories and
      those of their spouses'. METHOD: Participants included 5,074 married couples aged
      50 or older in the Health and Retirement Study in 2004-2010. Participants were
      categorized into 4 physical activity trajectories (i.e., stable active, adopters,
      relapsers, and stable sedentary) using confirmatory latent class growth analysis.
      Individuals' trajectory memberships were predicted by their spouses' memberships,
      together with recent diseases and functional difficulties of both couple members.
      RESULTS: In the main, corresponding husbands' trajectories predicted wives'
      trajectories and vice versa. More functional difficulties predicted higher
      likelihoods of unfavorable trajectories among individuals but not of their
      spouses'. Among wives, more recent diseases predicted slightly more physical
      activity in subsequent data waves but not trajectory memberships. DISCUSSION:
      Results supported spousal concordance in physical activity trajectories. The
      negative impact of functional difficulties was considerably contained within
      individuals. Increases in physical activity after acquiring diseases among wives
      were small and short lived. More research is needed to understand the underlying
      processes, which can be used to improve the design of future physical activity
      interventions directed toward women, men, and couples.

PMID- 23873966
TI  - Age-related and depot-specific changes in white adipose tissue of growth hormone
      receptor-null mice.
AB  - Growth hormone receptor-null (GHR(-/-)) mice are dwarf, insulin sensitive, and
      long-lived in spite of increased adiposity. However, their adiposity is not
      uniform, with select white adipose tissue (WAT) depots enlarged. To study WAT
      depot-specific effects on insulin sensitivity and life span, we analyzed
      individual WAT depots of 12- and 24-month-old GHR(-) (/-) and wild-type (WT)
      mice, as well as their plasma levels of selected hormones. Adipocyte sizes and
      plasma insulin, leptin, and adiponectin levels decreased with age in both GHR(-)
      (/-) and WT mice. Two-dimensional gel electrophoresis proteomes of WAT depots
      were similar among groups, but several proteins involved in endocytosis and/or
      cytoskeletal organization (Ehd2, S100A10, actin), anticoagulation (S100A10,
      annexin A5), and age-related conditions (alpha2-macroglobulin, apolipoprotein A
      I, transthyretin) showed significant differences between genotypes. Because Ehd2
      may regulate endocytosis of Glut4, we measured Glut4 levels in the WAT depots of
      GHR(-) (/-) and WT mice. Inguinal WAT of 12-month-old GHR(-) (/-) mice displayed
      lower levels of Glut4 than WT. Overall, the protein changes detected in this
      study offer new insights into possible mechanisms contributing to enhanced
      insulin sensitivity and extended life span in GHR(-) (/-) mice. 

PMID- 23873968
TI  - The influence of ethnicity and gender on caregiver health in older New
      Zealanders.
AB  - OBJECTIVES: We examined the interrelationships between ethnicity, gender, and
      caregiving on the health of older New Zealanders. We hypothesized that those
      providing higher levels of care and more care across time would have poorer
      health outcomes and that these relationships would be moderated by ethnicity and
      gender. METHOD: A representative sample of participants (N = 2,155) aged 54-70
      years from the first 2 waves of the New Zealand Health, Work and Retirement study
      completed postal surveys in 2006 and 2008. Caregiving questions were adapted from
      the Australian Women's Health study, and health measures were derived from the
      SF36 Health Survey. RESULTS: Women and Maori (indigenous New Zealanders) were
      more likely to provide care than men and non-Maori. Respondents providing higher
      levels of care reported poorer mental health and this was particularly true of
      Maori and female caregivers. Male Maori caregivers providing the highest level of
      care reported the poorest mental health. Level of care was unrelated to physical
      health. There was minimal evidence for changes in health over time based on
      caregiver status. DISCUSSION: The poorer health of caregivers supports previous
      findings on the detrimental health effects of caregiving. Caregiving may have
      more detrimental effects on Maori health outcomes due to existing inequalities in
      health, barriers to formal support services, and the multiple roles of elder
      Maori.

PMID- 23873969
TI  - Central adaptation after optic neuritis: is the whole greater than the sum of its
      parts?

PMID- 23873970
TI  - Temporal reorganization to overcome monocular demyelination.
AB  - OBJECTIVE: To identify the source of delayed visual evoked potential (VEP)
      latencies in the fellow eyes of patients with optic neuritis (ON) and determine
      whether these latencies stem from clinically silent demyelination or reflect an
      adaptive process for synchronization with the affected eyes. METHODS: The study
      sample comprised 17 patients whom we followed for 12 to 26 months after
      unilateral first-ever ON diagnosis and 17 age-matched controls. To avoid
      confounding effects of axonal loss, only intact fellow eyes (except for VEPs)
      were included. Subjects underwent standard visual evaluation, motion perception,
      as well as static and time-constrained stereo tasks. Assessments included VEP,
      optical coherence tomography, high-resolution MRI, and diffusion tensor imaging.
      RESULTS: We observed delayed VEP peaks (P100) in both affected and fellow eyes.
      However, while these were derived from prolonged time-to-start in the affected
      eyes, supporting the existence of demyelination, time-to-start in the fellow eyes
      was intact. VEP latencies in the fellow eyes could not be explained by
      demyelinative lesions along postchiasmal pathways (assessed by diffusion tensor
      imaging). Delayed peaks in fellow eyes resulted from a wider waveform, which
      evolved over time and occurred with a concomitant decrease in the gap in time
      between VEP peaks of both eyes. These changes offered a functional advantage;
      synchronization of inputs highly correlated with improved time-constrained
      binocular perception. CONCLUSION: Delayed latencies in the fellow eyes may
      reflect adaptive mechanisms at the cortical level that improve binocular
      integration over time to adjust for the damage incurred. These data provide a
      unique demonstration of temporal reorganization that compensates for delayed
      transmittal of visual information to the cortex.

PMID- 23873971
TI  - Very low levels of education and cognitive reserve: a clinicopathologic study.
AB  - OBJECTIVE: We conducted a clinicopathologic study in a large population with very
      low levels of education to determine whether very few years of education could
      contribute to cognitive reserve and modify the relation of neuropathologic
      indices to dementia. METHODS: In this cross-sectional study, we included 675
      individuals 50 years of age or older from the Brazilian Aging Brain Study Group.
      Cognitive abilities were evaluated through a structured interview with an
      informant at the time of autopsy, including the Clinical Dementia Rating (CDR)
      scale. Neuropathologic examinations were performed using immunohistochemistry and
      following internationally accepted criteria. Multivariate linear regression
      models were conducted to determine whether the association between cognitive
      abilities (measured by CDR sum of boxes) and years of education was independent
      of sociodemographic variables and neuropathologic indices, including neuritic
      plaques, neurofibrillary tangles, lacunar infarctions, small-vessel disease, and
      Lewy bodies. In addition, interaction models were used to examine whether
      education modified the relation between neuropathologic indices and cognition.
      RESULTS: Mean education was 3.9 +/- 3.5 years. Formal education was associated
      with a lower CDR sum of boxes (beta = -0.197; 95% confidence interval -0.343, 
      0.052; p = 0.008), after adjustment for sociodemographic variables and
      neuropathologic indices. Furthermore, education modified the relationship of
      lacunar infarcts with cognitive abilities (p = 0.04). CONCLUSIONS: Even a few
      years of formal education contributes to cognitive reserve.

PMID- 23873972
TI  - Propofol-related infusion syndrome heralding a mitochondrial disease: case
      report.

PMID- 23873973
TI  - Intellectual disability and bleeding diathesis due to deficient CMP--sialic acid
      transport.
AB  - OBJECTIVE: To identify the underlying genetic defect in a patient with
      intellectual disability, seizures, ataxia, macrothrombocytopenia, renal and
      cardiac involvement, and abnormal protein glycosylation. METHODS: Genetic studies
      involved homozygosity mapping by 250K single nucleotide polymorphism array and
      SLC35A1 sequencing. Functional studies included biochemical assays for N
      glycosylation and mucin-type O-glycosylation and SLC35A1-encoded cytidine 5'
      monophosphosialic acid (CMP-sialic acid) transport after heterologous expression
      in yeast. RESULTS: We performed biochemical analysis and found combined N- and O
      glycosylation abnormalities and specific reduction in sialylation in this
      patient. Homozygosity mapping revealed homozygosity for the CMP-sialic acid
      transporter SLC35A1. Mutation analysis identified a homozygous c.303G > C
      (p.Gln101His) missense mutation that was heterozygous in both parents. Functional
      analysis of mutant SLC35A1 showed normal Golgi localization but 50% reduction in
      transport activity of CMP-sialic acid in vitro. CONCLUSION: We confirm an
      autosomal recessive, generalized sialylation defect due to mutations in SLC35A1.
      The primary neurologic presentation consisting of ataxia, intellectual
      disability, and seizures, in combination with bleeding diathesis and proteinuria,
      is discriminative from a previous case described with deficient sialic acid
      transporter. Our study underlines the importance of sialylation for normal CNS
      development and regular organ function.

PMID- 23873974
TI  - The semiology of tilt-induced psychogenic pseudosyncope.
AB  - OBJECTIVES: To provide a detailed semiology to aid the clinical recognition of
      psychogenic pseudosyncope (PPS), which concerns episodes of apparent transient
      loss of consciousness (TLOC) that mimic syncope. METHODS: We analyzed all
      consecutive tilt-table tests from 2006 to 2012 showing proven PPS, i.e., apparent
      TLOC had occurred without EEG changes or a decrease in heart rate (HR) or blood
      pressure (BP). We analyzed baseline characteristics, video data, EEG, ECG, and
      continuous BP measurements on a 1-second time scale. Data were compared with
      those of 69 cases of tilt-induced vasovagal syncope (VVS). RESULTS: Of 800 tilt
      table tests, 43 (5.4%) resulted in PPS. The majority (74%) were women. The median
      duration of apparent TLOC was longer in PPS (44 seconds) than in VVS (20 seconds,
      p < 0.05). During the event, the eyes were closed in 97% in PPS but in only 7% in
      VVS (p < 0.0001). A sudden head drop or moving down the tilt table was more
      common in PPS than in VVS (p < 0.01), but jerking movements occurred more
      frequently in VVS (p < 0.0001). In PPS, both HR and BP increased before and
      during apparent TLOC (p < 0.0001). CONCLUSIONS: PPS is clinically distinct from
      VVS and can be diagnosed accurately with tilt-table testing and simultaneous EEG
      monitoring. Compared with VVS, eye closure during the event, long periods of
      apparent TLOC, and high HR and BP are highly specific for PPS. Improved
      understanding of the semiology of PPS as a clinical entity is vital to ensure
      accurate diagnosis.

PMID- 23873975
TI  - Early seizure onset and dysplastic lesion extent independently disrupt cognitive
      networks.
AB  - OBJECTIVE: To determine the most important factors influencing neuropsychological
      performance in children with intractable epilepsy due to focal cortical dysplasia
      and the nature of the interaction among significant variables. METHODS: Surgical
      patients with histologically verified focal cortical dysplasia were
      retrospectively evaluated to determine the impact of histopathology, extent of
      lobar involvement, hemispheric laterality, age at onset, and duration of epilepsy
      on cognitive functioning. A composite neuropsychological variable was obtained by
      transforming data from 5 major cognitive domains using principal components
      analysis. Multiple regression was used to examine the unique contributions of
      predictor variables on composite cognition and Full Scale IQ. Data were
      qualitatively evaluated for nonstatistical trends. RESULTS: Poor cognitive
      outcomes were associated with early age at onset of epilepsy (AOE) and widespread
      dysplastic involvement. Extent of dysplasia and AOE together accounted for 35% of
      Full Scale IQ variance, and 21% of composite cognitive performance. Each factor
      contributed independently to cognitive dysfunction. CONCLUSIONS: Early AOE
      disrupts critical periods of development and leads to poor cognitive outcome, but
      children with multilobar dysplasia are likely to have diminished cognitive skills
      regardless of AOE. Later AOE is not expected to mitigate deficits because of
      widespread pathology, nor would a localized lesion be likely to mollify the
      developmental deficits resulting from early AOE.

PMID- 23873976
TI  - A randomized phase II clinical trial of high-dose nicotine patch therapy for
      smokeless tobacco users.
AB  - INTRODUCTION: Nicotine patch therapy has not been shown to be efficacious for
      increasing long-term (>=6 months) tobacco abstinence rates among smokeless
      tobacco (ST) users. Higher doses of nicotine patch therapy may be needed to
      increase tobacco abstinence rates in this population of tobacco users. METHODS:
      We randomized ST users who used >=3 cans/pouches per week to either 8 weeks of
      high-dose nicotine patch therapy (42mg/day) or matching placebo patch. Subjects
      were followed for 6 months after randomization. RESULTS: Fifty-two subjects were
      randomized. Compared with placebo, high-dose nicotine patch therapy was
      associated with significantly higher prolonged tobacco abstinence at end-of
      treatment (44% vs. 22%, odds ratio [OR] = 2.7, p = .050) and 3 months (40% vs.
      19%, OR = 2.9, p = .047). High-dose nicotine patch therapy was associated with
      significant weight gain attenuation among tobacco abstinence subjects at 3 months
      (p = .013) and 6 months (p = .018). Compared with placebo, high-dose nicotine
      patch therapy was associated with nonsignificantly lower nicotine withdrawal
      scores. Adverse events were not significantly increased with high-dose nicotine
      patch therapy. CONCLUSIONS: High-dose nicotine patch therapy is safe and
      increases short-term tobacco abstinence rates among ST users who use >=3
      cans/pouches per week. High-dose nicotine patch therapy is associated with
      significant long-term attenuation of weight gain. Future studies to investigate
      the long-term efficacy of high-dose nicotine patch therapy and the comparative
      efficacy of this approach compared with standard nicotine patch doses for ST
      users seems warranted.

PMID- 23873977
TI  - Smoking and adverse maternal and child health outcomes in Brazil.
AB  - INTRODUCTION: Numerous studies from high-income countries document the causal
      relationship between cigarette smoking during pregnancy and adverse maternal and
      child health (MCH) outcomes. Less research has been conducted in low and middle
      income countries, but a burgeoning literature can be found for Brazil. METHODS:
      We review Brazilian studies of the prevalence of maternal smoking, the relative
      risk of smoking-attributable adverse MCH outcomes, and present new estimates for
      these outcomes, using the attributable fraction method. RESULTS: We found that
      Brazilian studies of the relative risks of smoking-attributable adverse MCH
      outcomes were broadly consistent with previous reviews. Based on a comparison of
      maternal smoking over time, smoking during pregnancy has declined by about 50%
      over the last 20 years in Brazil. For 2008, we estimate that 5,352 cases of
      spontaneous abortion, 10,929 cases of preterm birth, 20,717 cases of low birth
      weight, and 29 cases of sudden infant death syndrome are attributable to maternal
      smoking. Between 1989 and 2008, the percent of smoking-attributable adverse MCH
      outcomes in Brazil was at least halved. CONCLUSIONS: The results show that over a
      20-year period, during which Brazil implemented numerous effective tobacco
      control measures, the country experienced a dramatic decrease in both maternal
      smoking prevalence and smoking-attributable adverse MCH outcomes. Countries that
      implement effective tobacco control measures can expect to reduce both maternal
      smoking and adverse MCH outcomes, thereby improving the public health.

PMID- 23873978
TI  - Do people serve as cues to smoke?
AB  - INTRODUCTION: Recent research has identified that the environments in which
      smoking has previously occurred can alone, in the absence of any explicit smoking
      stimuli (e.g., cigarettes, lighters), serve as cues that induce robust craving to
      smoke. The goal of the present study was to determine if people can similarly
      function as smoking and nonsmoking cues capable of directly affecting smokers'
      cue-induced craving. METHODS: Smokers (N = 72) borrowed cameras to take photos of
      the people in their lives around whom they do and do not smoke ("personal"
      smoking and nonsmoking people, PS and PN, respectively). Self-report and
      physiological cue reactivity to those photos were compared with smokers'
      reactivity to photos of people unknown to them ("standard" smoking and nonsmoking
      people, SS and SN, respectively). RESULTS: Results suggest that the people around
      whom smokers regularly smoke (PS) can alone function as cues capable of eliciting
      patterns of reactivity similar to that evoked by proximal and environment smoking
      cues, namely, increased craving to smoke, negative affect, and excitement. In
      contrast, the people around whom smokers do not smoke become associated with not
      smoking (PN) and serve a potential protective function by reducing craving and
      increasing calm. CONCLUSIONS: This novel investigation and its results have
      implications for promoting smoking cessation by developing strategies to manage a
      smoker's social environment.

PMID- 23873980
TI  - Nicotine withdrawal and dependence among smokers with a history of childhood
      abuse.
AB  - INTRODUCTION: Previous studies have found that those with a history of childhood
      abuse are more likely to smoke cigarettes than those without a history of abuse.
      Mechanisms underlying this greater prevalence are unclear. We examined whether
      current smokers with a history of childhood abuse reported greater levels of
      nicotine dependence and more severe nicotine withdrawal symptoms. METHODS: We
      analyzed data from a 2-wave, national, random-digit-dial survey of adult
      cigarette smokers (n = 751). We examined whether childhood physical, emotional,
      and sexual abuse were associated with greater levels of nicotine dependence.
      Among those who made a quit attempt (n = 368), we examined whether abuse was
      associated with more severe withdrawal symptoms recalled during the 14 months
      between surveys. For both dependence and withdrawal, we tested a mediation
      pathway through current serious mental illness (SMI). RESULTS: All 3 types of
      childhood abuse were associated with more severe withdrawal symptoms. These
      associations were partially mediated by SMI. Sexual abuse and physical abuse were
      directly associated with dependence, whereas emotional abuse was indirectly
      associated with dependence through SMI. CONCLUSIONS: All 3 forms of childhood
      abuse were associated with both dependence and withdrawal. The greater prevalence
      of smoking found among those with a history of childhood abuse may be explained
      by heightened vulnerability to nicotine dependence and withdrawal and may be
      partially due to comorbid mental illness.

PMID- 23873979
TI  - Cigarette smoking and quit attempts among injection drug users in Tijuana,
      Mexico.
AB  - INTRODUCTION: Injection drug use and cigarette smoking are major global health
      concerns. Limited data exist regarding cigarette smoking behavior and quit
      attempts among injection drug users (IDUs) in low- and middle-income countries to
      inform the development of cigarette smoking interventions. We conducted a cross
      sectional study to describe cigarette smoking behavior and quit attempts among
      IDUs in Tijuana, Mexico. METHODS: IDUs were recruited through community outreach
      and administered in-person interviews. Multivariable Poisson regression models
      were constructed to determine prevalence ratios (PRs) for quit attempts. RESULTS:
      Of the 670 participants interviewed, 601 (89.7%) were current smokers. Of these,
      median number of cigarettes smoked daily was 10; 190 (31.6%) contemplated
      quitting smoking in the next 6 months; 132 (22.0%) had previously quit for >=1
      year; and 124 (20.6%) had made a recent quit attempt (lasting >=1 day during the
      previous 6 months). In multivariable analysis, recent quit attempts were
      positively associated with average monthly income (>=3,500 pesos [US$280] vs.
      <1,500 pesos [US$120]; PR = 2.30; 95% CI = 1.57-3.36), smoking marijuana (PR =
      1.38; 95% CI = 1.01-2.90), and smoking heroin (PR = 1.85; 95% CI = 1.23-2.78),
      and they were negatively associated with number of cigarettes smoked daily (PR =
      0.96; 95% CI = 0.94-0.98). CONCLUSIONS: One out of 5 IDUs attempted to quit
      cigarette smoking during the previous 6 months. Additional research is needed to
      improve the understanding of the association between drug use patterns and
      cigarette smoking quit attempts, including the higher rate of quit attempts
      observed among IDUs who smoke marijuana or heroin compared with IDUs who do not
      smoke these substances.

PMID- 23873981
TI  - One-hour training for general practitioners in reducing the implementation gap of
      smoking cessation care: a cluster-randomized controlled trial.
AB  - INTRODUCTION: This study examined the effectiveness of low-intensity, practice
      tailored training for general practitioners (GPs) aimed at personal and
      organizational barriers that arise when routinely asking patients' smoking
      status, advising to quit, and arranging follow-up. METHODS: A cluster-randomized
      controlled trial with 49 GPs and 3,401 patients (677 smokers). Two patient groups
      participated: 2,068 patients (433 smokers) at baseline and 1,333 patients (244
      smokers) postintervention. At follow-up, 225 smokers of both groups participated.
      The primary outcome was GP smoking cessation counseling (asking about smoking
      status, advising to quit, prescribing pharmacotherapy, and referring for
      behavioral support). Secondary outcomes were GPs' attitudes toward smoking
      cessation care, patients' intention to quit, and long-term quit rates. Outcomes
      were measured with GP self-report and patient report. RESULTS: Patients of
      trained GPs reported more often being asked about smoking behavior compared with
      patients of untrained GPs (OR = 1.94, 95% CI = 1.45-2.60). According to GP self
      report, the training increased the provision of quit-smoking advices (difference
      0.56 advice per day; 95% CI = 0.13-0.98) and the ability and intention of
      providing smoking cessation care. We found no effect on GPs' arrangement of
      follow-up, smokers' intention to quit, and long-term quit rates. CONCLUSIONS:
      After 1 hour of training, we found significant differences between trained and
      untrained GPs on the frequency in which they asked about smoking (patient
      reported) and advised smokers to quit (GP self-reported). The training did not
      increase prescriptions of pharmacotherapy, referrals to behavioral support, or
      quit rates. Future training methods should focus on the GPs' ability, tools, and
      skills to arrange follow-up to ensure intensive smoking cessation support.

PMID- 23873984
TI  - Archer dermatitis: a new case of allergic contact dermatitis.

PMID- 23873985
TI  - Healthy worker survivor bias: implications of truncating follow-up at employment
      termination.
AB  - OBJECTIVES: The healthy worker survivor effect is a bias that occurs in
      occupational studies when less healthy workers are more likely to reduce their
      workplace exposures. When variables on the pathway from health status to exposure
      are measured, g-methods can avoid this bias. However, studies in which follow-up
      ends at employment termination have additional potential for selection bias. This
      paper examines the structure of the healthy worker survivor effect, compares
      results with and without censoring at employment termination, and addresses how
      to prevent bias when such censoring occurs. METHODS: G-estimation of structural
      accelerated failure time models was applied in the United Autoworkers-General
      Motors cohort study to examine relationships between metalworking fluid exposure
      and cause-specific mortality. Subjects were followed from hire through 1994,
      regardless of employment status. To answer the central question, g-estimation
      analysis was repeated after truncating at employment termination and censoring
      outcomes that occurred thereafter, with adjustment for censoring by inverse
      probability weighting. RESULTS: Using full follow-up time, HRs were estimated for
      all-cause mortality (1.09), ischaemic heart disease death (1.19), and death from
      any cancer (1.09), comparing 5 years of metalworking fluid exposure to no
      exposure. For all three outcomes, the HR estimates based on data censored at
      termination of employment were below 1 (respectively, 0.92, 0.97, 0.79).
      CONCLUSIONS: In this application, g-estimation together with weighting did not
      prevent selection bias due to employment termination. However, the bias might be
      avoided in studies with measured health-related variables on the pathway from
      health status to employment termination.

PMID- 23873987
TI  - The solution structure of heparan sulfate differs from that of heparin:
      implications for function.

PMID- 23873989
TI  - Resolution of fatty liver and risk of incident diabetes.
AB  - CONTEXT: Fatty liver is associated with an increased risk of type 2 diabetes, but
      whether an increased risk remains in people in whom fatty liver resolves over
      time is not known. OBJECTIVE: The objective of the study was to assess the risk
      of incident diabetes at a 5-year follow-up in people in whom: 1) new fatty liver
      developed; 2) existing fatty liver resolved, and 3) fatty liver severity worsened
      over 5 years. DESIGN AND METHODS: A total of 13,218 people without diabetes at
      baseline from a Korean occupational cohort were examined at baseline and after 5
      years, using a retrospective study design. Fatty liver status was assessed at
      baseline and follow-up as absent, mild, or moderate/severe using standard
      ultrasound criteria. Adjusted odds ratios (aORs) and 95% confidence intervals
      (CIs) for incident diabetes at follow-up were estimated after controlling for
      multiple potential confounders. RESULTS: Two hundred thirty-four people developed
      incident diabetes. Over 5 years, fatty liver resolved in 828, developed in 1640,
      and progressed from mild to moderate/severe in 324 people. Resolution of fatty
      liver was not associated with a risk of incident diabetes [aOR 0.95 (95% CIs
      0.46, 1.96), P = .89]. Development of new fatty liver was associated with
      incident diabetes [aOR 2.49 (95% CI 1.49, 4.14), P < .001]. In individuals in
      whom severity of fatty liver worsened over 5 years (from mild to
      moderate/severe), there was a marked increase in the risk of incident diabetes
      [aOR 6.13 (2.56, 95% CI 14.68) P < .001 (compared with the risk in people with
      resolution of fatty liver)]. CONCLUSION: Change in fatty liver status over time
      is associated with markedly variable risks of incident diabetes.

PMID- 23873990
TI  - Liver fat has a stronger association with risk factors for type 2 diabetes in
      African-American compared with Hispanic adolescents.
AB  - CONTEXT: Although overweight and obese African-Americans (AAs) have less visceral
      adipose tissue (VAT) and liver fat (LF) than Hispanics, they have a similar risk
      for type 2 diabetes. OBJECTIVE: We examined ethnic differences in the association
      between VAT and LF with risk factors for type 2 diabetes to help explain this
      paradox. DESIGN: We conducted a cross-sectional study in an academic pediatric
      care facility. SUBJECTS: Subjects were overweight and obese AA (n = 131; 15.5 +/-
      3.3 years old) and Hispanic adolescents (n = 227; 14.7 +/- 3.0 years old). MAIN
      OUTCOME MEASURES: Outcome measures included insulin sensitivity (SI), acute
      insulin response (AIR), and disposition index (DI) by frequently sampled i.v.
      glucose tolerance test and minimal modeling. RESULTS: LF, not VAT, was inversely
      associated with SI, and the effect of high LF compared with low was more
      pronounced in AAs (P(interaction) < .05). In Hispanics, high LF was associated
      with a 24% lower SI (P < .01) and a 31% increase in AIR (P < .01) and was not
      associated with DI (P = .35). In AAs, high LF was associated with a 49% lower SI
      (P < .001), was not associated with an increase in AIR (P = .25), and was
      associated with a 42% lower DI (P < .01), indicating failure of compensatory
      insulin secretion/clearance in response to insulin resistance. Prediabetes
      changed the relationship between high/low LF and DI in Hispanics (P(interaction)
      = .002) but not AAs such that prediabetic Hispanics with high LF had a 43% lower
      DI (P = .03) with no difference in those without prediabetes (P = .06).
      CONCLUSIONS: LF has a stronger effect on SI compared with VAT. Our results
      suggest that the impact of high LF on poor beta-cell compensation is more
      pronounced in AAs. In Hispanics, the combination of high LF and prediabetes
      contributes to poor beta-cell compensation.

PMID- 23873991
TI  - Calcium-sensing receptor autoantibodies and idiopathic hypoparathyroidism.
AB  - CONTEXT: Data on calcium-sensing receptor autoantibodies (CaSRAbs) in
      hypoparathyroidism are variable. OBJECTIVE: We assessed the prevalence and
      significance of CaSRAbs in idiopathic hypoparathyroidism. DESIGN: This was a case
      control study. SUBJECTS: One hundred forty-seven patients with idiopathic
      hypoparathyroidism treated during 1998-2011 in a tertiary care setting and 348
      controls [healthy, n = 199; type 1 diabetes mellitus (T1DM), n = 99; and chronic
      lymphocytic thyroiditis (CLT), n = 50] participated in the study. METHODS: CaSRAb
      assays included Western blot with CaSR protein expressed in Escherichia coli or
      human embryonic kidney (HEK)-293 cells, immunoprecipitation (IP) using in vitro
      transcribed/translated protein, and indirect immunofluorescence on HEK293-CaSR.
      Functional significance was assessed by ERK1/2 phosphorylation. PTH and CaSR
      genes were sequenced for mutations. RESULTS: E coli-Western blot assay revealed
      16.3% CaSRAb positivity in idiopathic hypoparathyroidism, which was comparable
      with healthy subjects and CLT but significantly less than the T1DM controls. The
      prevalence of CaSRAbs on HEK293-Western blot (24.5%) against 150 kDa and/or 168
      kDa protein in hypoparathyroidism was significantly higher than the healthy
      subjects, T1DM, and CLT. IP assay showed CaSRAbs in 12.9% of the hypoparathyroid
      patients but not in controls. The sensitivity and specificity of CaSRAbs in E
      coli and HEK-293-CaSR Western blot and IP assays were 16.3% and 83.1%, 24.5% and
      88.9%, and 12.9% and 100%, respectively, and 42.1% of the cases detected were
      common in the IP assay and HEK293-Western blot. Duration of illness and
      coexistent autoimmunity were similar in patients with and without CaSRAbs. The
      CaSRAb-positive sera showed no immunofluorescence and phosphorylated ERK1/2
      activity. The CaSR gene sequence was normal in all patients. One of the patients
      showed a novel p.Met1_Asp6del mutation in the signal peptide region of the PTH
      gene. CONCLUSION: IP performed the best in detecting CaSRAbs in 12.9% of
      hypoparathyroid patients. Although CaSRAbs were functionally inert, its clinical
      relevance remains due to 100% specificity. Limited prevalence of CaSRAb suggests
      heterogeneity in the etiology of idiopathic hypoparathyroidism or the presence of
      CaSR epitopes other than those measured in the current study.

PMID- 23873992
TI  - Sex differences in neonatal mortality in Sarlahi, Nepal: the role of biology and
      environment.
AB  - BACKGROUND: Studies in South Asia have documented increased risk of neonatal
      mortality among girls, despite evidence of a biological survival advantage.
      Associations between gender preference and mortality are cited as reasons for
      excess mortality among girls. This has not, however, been tested in statistical
      models. METHODS: A secondary analysis of data from a population-based randomised
      controlled trial of newborn infection prevention conducted in rural southern
      Nepal was used to estimate sex differences in early and late neonatal mortality,
      with girls as the reference group. The analysis investigated which underlying
      biological factors (immutable factors specific to the newborn or his/her mother)
      and environmental factors (mutable external factors) might explain observed sex
      differences in mortality. RESULTS: Neonatal mortality was comparable by sex
      (Ref=girls; OR 1.06, 95% CI 0.92 to 1.22). When stratified by neonatal period,
      boys were at 20% (OR 1.20, 95% CI 1.02% to 1.42%) greater risk of early and girls
      at 43% (OR 0.70, 95% CI 0.51% to 0.94%) greater risk of late neonatal mortality.
      Biological factors, primarily respiratory depression and unconsciousness at
      birth, explained excess early neonatal mortality among boys. Increased late
      neonatal mortality among girls was explained by a three-way environmental
      interaction between ethnicity, sex and prior sibling composition (categorised as
      primiparous newborns, infants born to families with prior living boys or boys and
      girls, and infants born to families with only prior living girls). CONCLUSIONS:
      Risk of neonatal mortality inverted between the early and late neonatal periods.
      Excess risk of early neonatal death among boys was consistent with biological
      expectations. Excess risk for late neonatal death among girls was not explained
      by overarching gender preference or preferential care-seeking for boys as
      hypothesised, but was driven by increased risk among Madeshi girls born to
      families with only prior girls.

PMID- 23873993
TI  - TaMYB13-1, a R2R3 MYB transcription factor, regulates the fructan synthetic
      pathway and contributes to enhanced fructan accumulation in bread wheat.
AB  - Fructans are the major component of temporary carbon reserve in the stem of
      temperate cereals, which is used for grain filling. Three families of
      fructosyltransferases are directly involved in fructan synthesis in the vacuole
      of Triticum aestivum. The regulatory network of the fructan synthetic pathway is
      largely unknown. Recently, a sucrose-upregulated wheat MYB transcription factor
      (TaMYB13-1) was shown to be capable of activating the promoter activities of
      sucrose:sucrose 1-fructosyltransferase (1-SST) and sucrose:fructan 6
      fructosyltransferase (6-SFT) in transient transactivation assays. This work
      investigated TaMYB13-1 target genes and their influence on fructan synthesis in
      transgenic wheat. TaMYB13-1 overexpression resulted in upregulation of all three
      families of fructosyltransferases including fructan:fructan 1
      fructosyltransferase (1-FFT). A gamma-vacuolar processing enzyme (gamma-VPE1),
      potentially involved in processing the maturation of fructosyltransferases in the
      vacuole, was also upregulated by TaMYB13-1 overexpression. Multiple TaMYB13 DNA
      binding motifs were identified in the Ta1-FFT1 and Tagamma-VPE1 promoters and
      were bound strongly by TaMYB13-1. The expression profiles of these target genes
      and TaMYB13-1 were highly correlated in recombinant inbred lines and during stem
      development as well as the transgenic and non-transgenic wheat dataset, further
      supporting a direct regulation of these genes by TaMYB13-1. TaMYB13-1
      overexpression in wheat led to enhanced fructan accumulation in the leaves and
      stems and also increased spike weight and grain weight per spike in transgenic
      plants under water-limited conditions. These data suggest that TaMYB13-1 plays an
      important role in coordinated upregulation of genes necessary for fructan
      synthesis and can be used as a molecular tool to improve the high fructan trait. 

PMID- 23873994
TI  - Insights into the effects of polygalacturonase FaPG1 gene silencing on pectin
      matrix disassembly, enhanced tissue integrity, and firmness in ripe strawberry
      fruits.
AB  - Antisense-mediated down-regulation of the fruit-specific polygalacturonase (PG)
      gene FaPG1 in strawberries (Fragaria*ananassa Duch.) has been previously
      demonstrated to reduce fruit softening and to extend post-harvest shelf life,
      despite the low PG activity detected in this fruit. The improved fruit traits
      were suggested to be attributable to a reduced cell wall disassembly due to FaPG1
      silencing. This research provides empirical evidence that supports this
      assumption at the biochemical, cellular, and tissue levels. Cell wall
      modifications of two independent transgenic antisense lines that demonstrated a
      >90% reduction in FaPG1 transcript levels were analysed. Sequential extraction of
      cell wall fractions from control and ripe fruits exhibited a 42% decrease in
      pectin solubilization in transgenic fruits. A detailed chromatographic analysis
      of the gel filtration pectin profiles of the different cell wall fractions
      revealed a diminished depolymerization of the more tightly bound pectins in
      transgenic fruits, which were solubilized with both a chelating agent and sodium
      carbonate. The cell wall extracts from antisense FaPG1 fruits also displayed less
      severe in vitro swelling. A histological analysis revealed more extended cell
      cell adhesion areas and an enhanced tissue integrity in transgenic ripe fruits.
      An immunohistological analysis of fruit sections using the JIM5 antibody against
      low methyl-esterified pectins demonstrated a higher labelling in transgenic fruit
      sections, whereas minor differences were observed with JIM7, an antibody that
      recognizes highly methyl-esterified pectins. These results support that the
      increased firmness of transgenic antisense FaPG1 strawberry fruits is
      predominantly due to a decrease in pectin solubilization and depolymerization
      that correlates with more tightly attached cell wall-bound pectins. This limited
      disassembly in the transgenic lines indicates that these pectin fractions could
      play a key role in tissue integrity maintenance that results in firmer ripe
      fruit. 

PMID- 23873995
TI  - Shrinking the hammer: micromechanical approaches to morphogenesis.
AB  - Morphogenesis, the remarkable process by which a developing organism achieves its
      shape, relies on the coordinated growth of cells, tissues, and organs. While the
      molecular and genetic basis of morphogenesis is starting to be unravelled,
      understanding shape changes is lagging behind. Actually, shape is imposed by the
      structural elements of the organism, and the translation of cellular activity
      into morphogenesis must go through these elements. Therefore, many methods have
      been developed recently to quantify, at cellular resolution, the properties of
      the main structural element in plants, the cell wall. As plant cell growth is
      restrained by the cell wall and powered by turgor pressure, such methods also
      address the quantification of turgor. These different micromechanical approaches
      are reviewed here, with a critical assessment of their strengths and weaknesses,
      and a discussion of how they can help us understand the regulation of growth and
      morphogenesis. 

PMID- 23873996
TI  - A meta-analysis of responses of canopy photosynthetic conversion efficiency to
      environmental factors reveals major causes of yield gap.
AB  - Improving plant energy conversion efficiency (epsilonc) is crucial for increasing
      food and bioenergy crop production and yields. Using a meta-analysis, the effects
      of greenhouse gases, weather-related stresses projected to intensify due to
      climate change, and management practices including inputs, shading, and
      intercropping on epsilonc were statistically quantified from 140 published
      studies to identify where improvements would have the largest impact on closing
      yield gaps. Variation in the response of epsilonc to treatment type and dosage,
      plant characteristics, and growth conditions were also examined. Significant mean
      increases in epsilonc were caused by elevated [CO2] (20%), shade (18%), and
      intercropping (15%). epsilonc increased curvilinearly up to 55% with nitrogen
      additions whereas phosphorus application was most beneficial at low levels.
      Significant decreases in epsilonc of -8.4% due to elevated [O3], -16.8% due to
      water stress, and -6.5% due to foliar damage were found. A non-significant
      decrease in epsilonc of -17.3% was caused by temperature stress. These results
      identify the need to engineer greater stress tolerance and enhanced responses to
      positive factors such as [CO2] and nitrogen to improve average yields and yield
      potential. Optimizing management strategies will also enhance the benefits
      possible with intercropping, shade, and pest resilience. To determine optimal
      practices for epsilonc improvement, further studies should be conducted in the
      field since several responses were exaggerated by non-field experimental
      conditions. 

PMID- 23873998
TI  - Evaluation of reduced-tillering (tin) wheat lines in managed, terminal water
      deficit environments.
AB  - Small or shrivelled wheat kernels (screenings) that reduce crop value are
      commonly produced in terminal drought environments. The aim of this study was to
      establish whether the incorporation of the tiller inhibition (tin) gene would
      contribute to maintenance of kernel weight and reductions in screenings under
      terminal water deficit. Five Silverstar near-isogenic lines contrasting in high
      and low tiller potential and their recurrent Silverstar parent were established
      at two plant densities under managed terminal water deficit (mild and severe) and
      irrigated conditions. With irrigation (grain yield of 5.6 t ha(-1)), kernels of
      all lines weighed ~31 mg, with restricted-tillering (R-tin) lines producing an
      average 15% lower grain yield. Under both mild and severe terminal water deficit
      (4.1 t ha(-1) and 2.8 t ha(-1)), free-tillering lines had relatively high
      screenings ranging from 11.9% to 16.2%. Compared with free-tillering lines, R-tin
      lines maintained large kernel weight (~29 mg kernel(-1)) and had 29% and 51%
      fewer screenings under the two stresses, and a significantly greater (+11%) grain
      yield under mild stress. Higher kernel weights in tin lines were realized even
      with the greater kernel number per spike. The higher kernel weight of the R-tin
      lines under stress conditions was associated with greater anthesis biomass and
      increased stem water-soluble carbohydrates, ensuring more assimilate for later
      translocation to filling grain. The incorporation of the tin gene into genetic
      material adapted to the target environments provides scope for improvement in
      both grain yield and kernel weight, and a reduction in screenings in terminal
      water deficit environments.

PMID- 23873997
TI  - Quantification of the effects of VRN1 and Ppd-D1 to predict spring wheat
      (Triticum aestivum) heading time across diverse environments.
AB  - Heading time is a major determinant of the adaptation of wheat to different
      environments, and is critical in minimizing risks of frost, heat, and drought on
      reproductive development. Given that major developmental genes are known in
      wheat, a process-based model, APSIM, was modified to incorporate gene effects
      into estimation of heading time, while minimizing degradation in the predictive
      capability of the model. Model parameters describing environment responses were
      replaced with functions of the number of winter and photoperiod (PPD)-sensitive
      alleles at the three VRN1 loci and the Ppd-D1 locus, respectively. Two years of
      vernalization and PPD trials of 210 lines (spring wheats) at a single location
      were used to estimate the effects of the VRN1 and Ppd-D1 alleles, with validation
      against 190 trials (~4400 observations) across the Australian wheatbelt. Compared
      with spring genotypes, winter genotypes for Vrn-A1 (i.e. with two winter alleles)
      had a delay of 76.8 degree days ( degrees Cd) in time to heading, which was
      double the effect of the Vrn-B1 or Vrn-D1 winter genotypes. Of the three VRN1
      loci, winter alleles at Vrn-B1 had the strongest interaction with PPD, delaying
      heading time by 99.0  degrees Cd under long days. The gene-based model had root
      mean square error of 3.2 and 4.3 d for calibration and validation datasets,
      respectively. Virtual genotypes were created to examine heading time in
      comparison with frost and heat events and showed that new longer-season varieties
      could be heading later (with potential increased yield) when sown early in
      season. This gene-based model allows breeders to consider how to target gene
      combinations to current and future production environments using parameters
      determined from a small set of phenotyping treatments. 

PMID- 23873999
TI  - Growth response and acclimation of CO2 exchange characteristics to elevated
      temperatures in tropical tree seedlings.
AB  - Predictions of how tropical forests will respond to future climate change are
      constrained by the paucity of data on the performance of tropical species under
      elevated growth temperatures. In particular, little is known about the potential
      of tropical species to acclimate physiologically to future increases in
      temperature. Seedlings of 10 neo-tropical tree species from different functional
      groups were cultivated in controlled-environment chambers under four day/night
      temperature regimes between 30/22  degrees C and 39/31  degrees C. Under well
      watered conditions, all species showed optimal growth at temperatures above those
      currently found in their native range. While non-pioneer species experienced
      catastrophic failure or a substantially reduced growth rate under the highest
      temperature regime employed (i.e. daily average of 35  degrees C), growth in
      three lowland pioneers showed only a marginal reduction. In a subsequent
      experiment, three species (Ficus insipida, Ormosia macrocalyx, and Ochroma
      pyramidale) were cultivated at two temperatures determined as sub- and
      superoptimal for growth, but which resulted in similar biomass accumulation
      despite a 6 degrees C difference in growth temperature. Through reciprocal
      transfer and temperature adjustment, the role of thermal acclimation in
      photosynthesis and respiration was investigated. Acclimation potential varied
      among species, with two distinct patterns of respiration acclimation identified.
      The study highlights the role of both inherent temperature tolerance and thermal
      acclimation in determining the ability of tropical tree species to cope with
      enhanced temperatures. 

PMID- 23874000
TI  - Mesoscale modeling of multi-protein-DNA assemblies: the role of the catabolic
      activator protein in Lac-repressor-mediated looping.
AB  - DNA looping plays a key role in the regulation of the lac operon in Escherichia
      coli. The presence of a tightly bent loop (between sequentially distant sites of
      Lac repressor protein binding) purportedly hinders the binding of RNA polymerase
      and subsequent transcription of the genetic message. The unexpectedly favorable
      binding interaction of this protein-DNA assembly with the catabolic activator
      protein (CAP), a protein that also bends DNA and paradoxically facilitates the
      binding of RNA polymerase, stimulated extension of our base-pair level theory of
      DNA elasticity to the treatment of DNA loops formed in the presence of several
      proteins. Here we describe in detail a procedure to determine the structures and
      free energies of multi-protein-DNA assemblies and illustrate the predicted
      effects of CAP binding on the configurations of the wild-type 92-bp Lac repressor
      mediated O3-O1 DNA loop. We show that the DNA loop adopts an antiparallel
      orientation in the most likely structure and that this loop accounts for the
      published experimental observation that, when CAP is bound to the loop, one of
      the arms of LacR binds to an alternative site that is displaced from the original
      site by 5 bp.

PMID- 23874001
TI  - Micromechanics and Structural Response of Functionally Graded, Particulate
      Matrix, Fiber-Reinforced Composites.
AB  - Reinforcement of fibrous composites by stiff particles embedded in the matrix
      offers the potential for simple, economical functional grading, enhanced response
      to mechanical loads, and improved functioning at high temperatures. Here, we
      consider laminated plates made of such a material, with spherical reinforcement
      tailored by layer. The moduli for this material lie within relatively narrow
      bounds. Two separate moduli estimates are considered: a "two-step" approach in
      which fibers are embedded in a homogenized particulate matrix, and the Kanaun
      Jeulin (2001) approach, which we re-derive in a simple way using the Benveniste
      (1988) method. Optimal tailoring of a plate is explored, and functional grading
      is shown to improve the performance of the structures considered. In the example
      of a square, simply supported, cross-ply laminated panel subjected to uniform
      transverse pressure, a modest functional grading offers significant improvement
      in performance. A second example suggests superior blast resistance of the panel
      achieved at the expense of only a small increase in weight.

PMID- 23874002
TI  - Shielding effects in polymer-polymer reactions. V. Concentration dependence of
      contact formation between star-branched and linear chains.
AB  - By use of the Dissipative Particle Dynamics (DPD) simulation technique mixtures
      of star-branched (arm number F = 4) and linear chains in athermal (good) solvent
      are analyzed regarding probabilities for intermolecular contacts of various
      reactive sites within different polymer coils. The accompanying sterical
      hindrances are described in the framework of shielding factors in order to
      investigate reactions and side reactions in radical polymerization and other
      techniques that involve polymer-polymer coupling. The shielding factors are
      studied as a function of total concentration from high dilution up to the bulk
      for different chain lengths of star-shaped and linear chains. Results indicate
      that their concentration dependence can be described by a power law for systems
      above the overlap concentration, whereas the chain length dependence vanishes
      when extrapolating to infinite chain lengths in that concentration range. Also
      the influence of the ratio of star chains and linear chains is studied for
      various concentrations.

PMID- 23874003
TI  - Presidential address: doing our part to ensure the future of academic medicine.

PMID- 23874006
TI  - Methotrexate in rheumatoid arthritis: a quarter century of development.
AB  - Methotrexate (MTX) is now the most popular drug worldwide for the treatment of
      rheumatoid arthritis. Low-dose, weekly MTX (10 to 25 mg/wk) used as either
      monotherapy or in combination with other drugs has a superior efficacy profile as
      defined in placebo-controlled trials and comparable efficacy to other drugs
      including anti-TNF therapy. At 1 year, one third of patients on MTX have no
      radiographic progression and even greater effects are seen when combined with
      targeted biological therapies. MTX is well tolerated; gastrointestinal toxicity
      is the most common toxicity with rarely bone marrow, lung, or liver toxicity. MTX
      therapy has been a major advance in the treatment of rheumatoid arthritis and is
      now the cornerstone of therapy. 

PMID- 23874007
TI  - Cracking the code for thyroid hormone signaling.
AB  - Cells are not passive bystanders in the process of hormonal signaling and instead
      can actively customize hormonal action. While diffusing from the plasma membrane
      to the nucleus, thyroid hormone is modified via the action of thioredoxin fold
      containing selenoenzymes known as deiodinases. Whereas the type II deiodinase
      (D2) converts the prohormone thyroxine (T4) to the biologically active T3, the
      type III deiodinase (D3) converts it to reverse T3, an inactive metabolite. D3
      also inactivates T3 to T2, terminating thyroid hormone action. Therefore, D2
      provides cells with the ability to produce extra amounts of T3 and thus enhances
      thyroid hormone signaling. In contrast, expression of D3 results in the opposite
      action. In addition, the D2 protein is unique in that it can be switched off and
      on via an ubiquitin-regulated mechanism, triggered by catalysis of T4. Induction
      of D2 enhances local thyroid hormone signaling and energy expenditure during
      activation of brown adipose tissue by cold exposure or high fat diet. On the
      other hand, induction of D3 in myocardium and brain during ischemia and hypoxia
      decreases energy expenditure as part of a homeostatic mechanism to slow down cell
      metabolism in the face of limited O2 supply. 

PMID- 23874008
TI  - Signal versus noise on the wards: what "messages" from the hidden curriculum do
      medical students perceive to be importantly meaningful?
AB  - Interested in the hidden curriculum and the learning environment for
      professionalism at our school, a group of educators called the RIPPLE Team
      (Relationships in Positive Professional Learning Environments) created The
      Professionalism Journal for use by third-year medical students during their
      Internal Medicine and Psychiatry clerkships. The students are introduced to the
      online journal and encouraged to use it as a means to pause, reflect on the
      events of the day, and write about episodes or exchanges they find personally
      important and meaningful. They are informed that their journal entries will be de
      identified and used as the triggers for a facilitated and confidential discussion
      among their peers at the end of the clerkship. This article will report on the
      themes of the journal entries made by Internal Medicine clerks during one
      academic year. 

PMID- 23874009
TI  - The design and clinical development of inhibitors of glycosphingolipid synthesis:
      will invention be the mother of necessity?
AB  - The treatment of glycosphingolipid storage diseases by synthesis inhibition was
      first proposed 40 years ago as an alternative approach to enzyme replacement
      therapy. We have pursued this strategy through the rational design of potent and
      selective inhibitors of glucosylceramide synthase, the first step in
      glycosphingolipid synthesis. Eliglustat tartrate was the result of these efforts
      and is currently the focus of phase 3 trials for type 1 Gaucher disease. Phase 2
      studies showed a reduction in splenomegaly and hepatomegaly and improvements of
      anemia and thrombocytopenia at levels equivalent to or exceeding the historic
      response to imiglucerase. Structural analogues of eliglustat have also been
      designed that lack pgp-1 recognition and cross the blood brain barrier. These may
      have utility for central nervous system- based sphingolipidoses. Because
      glycosphingolipids are important regulators of receptor tyrosine kinases,
      glucosylceramide synthase inhibitors may also be beneficial for disorders such as
      type 2 diabetes mellitus and polycystic kidney disease. 

PMID- 23874013
TI  - The epigenetic basis of common human disease.

PMID- 23874010
TI  - Cryptococcal infections in non-HIV-infected patients.
AB  - Infections due to Cryptococcus species occur globally and in a wide variety of
      hosts, ranging from those who are severely immunosuppressed to those who have
      phenotypically "normal" immune systems. Approximately 1 million cases of
      cryptococcosis occur throughout the world, and is it estimated that there are
      650,000 associated deaths annually. Most of these cases occur among patients with
      advanced HIV disease, but a growing number occur among solid organ transplant
      recipients and others receiving exogenous immunosuppression, patients with innate
      and acquired immunodeficiency, and otherwise immunologically normal hosts. Much
      of our recent knowledge is solely derived from clinical experience over the last
      2 to 3 decades of cryptococcosis among HIV-infected patients. However, based on
      recent observations, it is clear that there are substantial differences in the
      epidemiology, clinical features, approaches to therapy, and outcome when
      comparing HIV-infected to non-HIV-infected individuals who have cryptococcosis.
      If one carefully examines cryptococcosis in the three largest subgroups of
      patients based on host immune status, specifically, those with HIV, solid organ
      transplant recipients, and those who are non-HIV, non-transplant (NHNT) infected
      persons, then one can observe very different risks for infection, varied clinical
      presentations, long-term complications, mortality, and approaches to therapy.
      This article focuses on cryptococcosis in the non-HIV-infected patient, including
      a brief review of ongoing events in the Pacific Northwest of the United States
      and Canada relative to the outbreak of Cryptococcus gattii infections among a
      largely immunologically normal population, and highlights some of the key
      insights and questions which have emerged as a result of these important new
      observations. 

PMID- 23874014
TI  - The stem cell wars: a dispatch from the front.
AB  - The development of human embryonic stem cell (hESC) lines in 1998 offered the
      prospect of a new era of regenerative medicine in which cell therapy might cure
      intractable diseases such as type 1 diabetes, Parkinson's disease, and spinal
      cord injury. The Bush Administration decision in 2001 to restrict federal funding
      of hESC research touched off a controversy that continues to the present. One
      response to the Bush policy was establishment of state stem cell research funding
      programs, notably the California Institute of Regenerative Medicine (CIRM). As
      Director of the National Institute of Diabetes, Digestive, and Kidney Diseases
      (NIDDK) and Vice Chair of the National Institutes of Health (NIH) Stem Cell Task
      Force, and now as a member of the Empire State Stem Cell Funding Board and member
      of an Institute of Medicine (IOM) committee charged with evaluation of the CIRM,
      I have had the opportunity to gain a first-hand perspective of the field. Here I
      present my impressions of the legal and science policy debates and selectively
      summarize research progress toward the hoped-for cures. 

PMID- 23874016
TI  - The complex dynamics of antimicrobial activity in the human gastrointestinal
      tract.
AB  - The human gastrointestinal tract is a complex environment of mutualistic
      associations. As bacteria form a major component of fecal content, the natural
      balance of the colon can be significantly altered by exposure to antimicrobial
      agents. However, the effects of antimicrobial therapy on fecal content are
      difficult to predict and can at times be quite surprising. The emergence and
      spread of vancomycin-resistant enterococci are cases in point. Resistance to the
      glycopeptide vancomycin emerged in enterococci (primarily in Enterococcus
      faecium) in the late 1980s in both Europe and the United States. In Europe, this
      emergence was tied to the use of the glycopeptide antibiotic avoparcin to promote
      growth in food animals and had little actual impact on hospital infections. In
      the United States, where avoparcin has never been licensed, vancomycin-resistant
      enterococci (VRE) emerged as a major hospital pathogen. Paradoxically, while the
      initial entry of the vancomycin resistance determinants into enterococci was
      almost certainly driven by high fecal concentrations of vancomycin associated
      with treatment for Clostridium difficile colitis, clinical infection and
      outbreaks were more frequently tied to use of extended-spectrum cephalosporins
      and agents with potent activity against anaerobic bacteria. Animal studies
      suggest that cephalosporins promote initial VRE colonization because of the
      frequent concomitant high-level resistance to beta-lactam antibiotics expressed
      by these strains. Anti-anaerobic agents appear to increase the output of VRE in
      the feces, presumably by reducing the number of competitive flora in the colon.
      Intravenously administered vancomycin appears to have little impact because it
      achieves negligible concentrations in the feces after short courses. Thus, the
      spread of glycopeptide resistance in enterococci is promoted in a large measure
      by the administration of non-glycopeptide antibiotics. 

PMID- 23874015
TI  - Adaptive responses to tissue injury: role of heme oxygenase-1.
AB  - Tissue injury may result as a consequence of a physical, chemical, or biological
      insult. Such injury recruits an adaptive response to restore homeostasis and
      protect against further injury. One of the most prompt protective and adaptive
      responses by all tissues is the robust activation of the highly inducible, anti
      inflammatory, anti-oxidant, and anti-apoptotic protein, heme oxygenase-1 (HO-1).
      HO-1, a microsomal enzyme, catalyzes the breakdown of pro-oxidant heme, which is
      released from heme proteins to equimolar quantities of iron, carbon monoxide, and
      biliverdin. Biliverdin is converted to bilirubin by biliverdin reductase. The
      beneficial effects of HO-1 expression are not merely due to heme degradation but
      are also attributed to the cytoprotective properties of the byproducts of the
      reaction. Manipulation of this enzymatic system in a myriad of disease models has
      provided substantial evidence to support its role as a cytoprotective enzyme and
      is therefore an emerging therapeutic molecule. 

PMID- 23874017
TI  - Circulating permeability factor suPAR: from concept to discovery to clinic.
AB  - Kidney filtration functions through a hydrostatically driven multicellular
      barrier that includes visceral epithelial cells termed podocytes. These cells
      have delicate foot processes by which they ensure proper generation of urine.
      Most forms of chronic kidney disease start with disruption of podocytes, allowing
      for a breakdown of kidney barrier function and loss of plasma proteins from the
      blood into the urine (proteinuria). A classic podocyte disease is focal segmental
      glomerulosclerosis (FSGS) which progresses from podocyte injury to chronic kidney
      disease (CKD) and end-stage renal disease (ESRD) in a well-defined
      histopathological pattern. FSGS can recur after kidney transplantation in 30% or
      more cases, affecting both children and adults with rapid disease onset. This
      scenario has led credence to the concept that FSGS is caused by one or more
      circulating blood factor (s) that in turn cause podocyte injury. Decades of
      search for viable circulating permeability factor candidates have sparked
      research in this area. Recently, soluble urokinase plasminogen activator receptor
      (suPAR) was identified in a majority of patients with FSGS as a soluble factor
      that acts through binding to and activating podocyte beta 3 integrin. These
      observations show promise for novel therapeutic development to eliminate a
      portion of FSGS cases. 

PMID- 23874018
TI  - Physiologic and pathophysiologic roles of cyclooxygenase-2 in the kidney.
AB  - In the mammalian kidney, prostaglandins are important mediators of physiologic
      processes, including modulation of vascular tone and salt and water.
      Prostaglandins arise from enzymatic metabolism of free arachidonic acid (AA),
      which is cleaved from membrane phospholipids by phospholipase A2 activity. The
      cyclooxygenase (COX) enzyme system is a major pathway for metabolism of
      arachidonic acid in the kidney. Cyclooxygenases are the enzymes responsible for
      the initial conversion of AA to PGG2 and subsequently to PGH2, which serves as
      the precursor for subsequent metabolism by specific prostaglandin and thromboxane
      synthases. In addition to high levels of expression of the "constitutive" rate
      limiting enzyme responsible for prostanoid production, COX-1, the "inducible"
      isoform of cyclooxygenase, COX-2, is also constitutively expressed in the kidney
      and is highly regulated in response to alterations in intravascular volume.
      Prostaglandins and thromboxane A2 exert their biological functions predominantly
      through activation of specific 7-transmembrane G-protein-coupled receptors. We
      and others have shown that COX-2-derived prostaglandins exert important
      physiologic functions in maintenance of renal blood flow, mediation of renin
      release, and regulation of sodium excretion. In addition to physiologic
      regulation of prostanoid production in the kidney, increases in prostanoid
      production are also observed in a variety of inflammatory renal injuries, and we
      have found a role for COX metabolites to serve as mediators of inflammatory
      injury in renal disease. 

PMID- 23874019
TI  - Targeting deacetylases to improve outcomes after allogeneic bone marrow
      transplantation.
AB  - Graft-versus-host disease (GVHD) is the major complication of allogeneic bone
      marrow transplantation (BMT). GVHD is a complex immunologically mediated
      biological process. Recent data have shown that histone deacetylase inhibitors
      (HDACis) have potent anti-inflammatory effects. We have been studying the role of
      acetylation through inhibition of histone deacetylases (HDACs) in modulating
      immunity, specifically, GVHD. HDAC inhibition regulates GVHD, at least in part,
      through suppression of the function of host antigen presenting cells such as
      dendritic cells (DCs). HDACis reduce DC responses by enhancing the expression of
      indoleamine 2,3 dioxygenase (IDO) in a STAT-3-dependent manner. They also alter
      the function of other immune cells such as T regulatory cells and NK cells, which
      also play important roles in the biology of GVHD. Based on these observations, a
      clinical trial has been launched to evaluate its impact on clinical GVHD. The
      clinical features, biology of GVHD, the experimental studies with HDACis, and
      preliminary observations from humans are discussed. 

PMID- 23874020
TI  - Covert operations: cancer's many subversive tactics in overcoming host defenses.
AB  - In an effort to use the patient's T cells to fight his or her own cancer, we
      inadvertently discovered a distinctive form of tumor-induced immune suppression.
      T cells from tumor-bearing patients are often defective in signaling. They lack
      the zeta chain of the T-cell receptor and the src kinases crucial for its
      downstream effects including lck. They truncate the carboxy terminal of the p50
      NF-kappaB transcription factor. At the population level, CD4 T cells are
      polarized toward the Th2 subtype and inhibitory Tregs expand. These T cells can
      recover after several days of culture outside of the tumor-bearing host
      environment. The effect is mediated by one or more factors made by the tumor
      given that the same T-cell defects occur in mice with tumors implanted in hollow
      fibers that never directly contact cells of the host. Several promising
      strategies may overcome these immunosuppressive effects. 

PMID- 23874022
TI  - Psychological responses and resilience of people and communities impacted by the
      deepwater horizon oil spill.
AB  - On April 20, 2010, the BP Deepwater Horizon oil platform in the United States
      Gulf of Mexico exploded, killing 11 persons and resulting in a 5-month spill of
      more than 206 million gallons of oil, affecting more than 950 miles of shoreline.
      Our initial studies in Baldwin County, Alabama, and Franklin County, Florida,
      conducted while the oil spill was still in progress, showed high levels of
      clinically significant anxiety and depression in persons living in coastal
      communities. Income loss was the most significant driver of anxiety and
      depression, rather than direct influx or contact with oil. Ongoing studies of
      these groups and their communities have been conducted under the auspices of the
      National Institute of Environmental Health Sciences (NIEHS) Deepwater Horizon
      Research Consortium. A year after the spill, there was no significant change in
      levels of anxiety or depression in our cohort. Income loss continued to be
      associated with higher levels of psychopathology; findings were not associated
      with age, gender, education, or psychiatric history. Media exposure was
      associated with persistent hyperarousal. Findings support a model of chronic
      psychological disruption after the oil spill disaster. Community studies
      underscored the "corrosive" nature of this type of man-made disaster (as compared
      with natural disasters that have hit the region), with particular concerns
      expressed about the compensation process administered by British Petroleum and
      the parties that followed. Our research highlights the very real and long-lasting
      impact of such disasters on individuals and communities, extending well beyond
      the areas where there was direct exposure to oil. 

PMID- 23874025
TI  - The Bert and Peggy Dupont Lecture. Discovering science stories.

PMID- 23874021
TI  - Closing the loop on inflammation and atherothrombosis: why perform the CIRT and
      CANTOS trials?
AB  - Inflammation contributes to all phases of the atherothrombotic process, patients
      with elevated inflammatory biomarkers such as high-sensitivity C-reactive protein
      (hsCRP) have increased cardiovascular risk, and recent work directly implicates
      the interleukin-1 (IL-1) and interleukin-6 (IL-6) pathways in atherogenesis. Yet,
      it remains unknown whether targeted inhibition of inflammation will reduce
      cardiovascular event rates. To address directly this fundamental hypothesis, our
      research group has initiated two large-scale, randomized, placebo-controlled
      trials using targeted anti-inflammatory agents for the secondary prevention of
      myocardial infarction. The first trial, the Cardiovascular Inflammation Reduction
      Trial (CIRT), has been funded by the NHLBI and will evaluate whether low-dose
      methotrexate (target dose, 20 mg/wk) as compared to placebo will reduce major
      vascular events among a group of post-myocardial infarction patients with either
      diabetes or metabolic syndrome, groups known to have high risk on the basis of a
      persistent pro-inflammatory response. CIRT is based, in part, on observational
      evidence of reduced vascular event rates among those treated with methotrexate in
      the setting of rheumatoid arthritis or psoriatic arthritis and on the ability of
      methotrexate to reduce TNF, IL-6, and CRP levels. The second trial, the
      Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS), will evaluate
      whether interleukin-1beta (IL-1beta) inhibition as compared to placebo can reduce
      rates of recurrent myocardial infarction, stroke, and cardiovascular death among
      stable coronary artery disease patients who remain at high vascular risk due to
      persistent elevations of hsCRP (_2 mg/L) despite contemporary secondary
      prevention strategies. Canakinumab is a human monoclonal antibody that
      selectively neutralizes IL-1beta, a pro-inflammatory cytokine that plays multiple
      roles in the atherothrombotic process and that undergoes activation by the NLRP3
      inflammasome, a process promoted by cholesterol crystals that in turn leads
      directly to increased production of IL-1 and IL-6. Together, CIRT and CANTOS will
      enroll more than 25,000 patients worldwide and provide a fundamental test of the
      inflammatory hypothesis of atherothrombosis. 

PMID- 23874028
TI  - Developing physician-scientists: a perspective.

PMID- 23874029
TI  - Anemia in the elderly.
AB  - As the population ages, increasing attention has become focused on the prevalence
      of anemia in elderly individuals. Anemia occurs in more than 10% of individuals
      who are older than the age of 65 years, and it increases to more than 50% in
      individuals who are older than the age of 80 years. Although the anemia is
      typically mild and unlikely to result in symptoms, it is uniformly associated
      with increased morbidity and mortality as assessed in large cohort studies.
      Anemia is an independent predictor of these adverse outcomes both in healthy
      community-dwelling subjects and in patients with significant co-morbidities.
      Efforts to understand the pathophysiology of anemia in this population,
      especially the one third of patients with "unexplained" anemia, have focused on
      the potential contributions of inflammatory pathways, erythropoietin resistance,
      and changes in hematopoietic stem cells to the age-dependent decrease in red cell
      mass. We would argue that these pathways are closely interrelated and combine to
      lead to anemia in aging individuals. This brief review summarizes the current
      understanding of this entity and our studies aimed at further delineating its
      pathophysiology. 

PMID- 23874030
TI  - An epistemology for clinical medicine: an argument for reflection on the ends of
      medical practice and ways of knowing with implications for the selection and
      training of physician.
AB  - Today physicians and scientists have a detailed understanding of human biology
      and have developed diagnostic and therapeutic tools that were unimaginable a
      century ago. Yet physicians have provided care and counsel for more than 3000
      years. Some, such as Hippocrates and Osler, remain exemplars of the excellent
      physician. They did not have our scientific knowledge or tools, but they knew
      something important and performed some task of great value to their patients.
      What did they know and what did they do? This article explores the questions
      every ill patient asks, the timeless nature of patient as person, and the forms
      of non-factual knowing (described as know-how, know-what, know-who, and know-how
      it-feels) that are essential to patient care. From this, it is suggested that the
      combination of understanding, insight, and judgment used for practical action,
      what Aristotle called "phronesis," is the core competency of excellent physicians
      which has remained unchanged across the centuries. 

PMID- 23874031
TI  - The lung in liver disease: old problem, new concepts.
AB  - Liver dysfunction has been recognized to influence the lung in many different
      clinical situations, although the mechanisms for these effects are not well
      understood. One increasingly recognized interaction, the hepatopulmonary syndrome
      (HPS) occurs in the context of cirrhosis and results when alveolar microvascular
      dilation causes arterial gas exchange abnormalities and hypoxemia. HPS occurs in
      up to 30% of patients with cirrhosis and significantly increases mortality in
      affected patients. Currently, liver transplantation is the only curative therapy.
      Experimental biliary cirrhosis induced by common bile duct ligation (CBDL) in the
      rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS
      and has been contrasted with other experimental models of cirrhosis in which HPS
      does not develop. Microvascular dilation, intravascular monocyte infiltration,
      and angiogenesis in the lung have been identified as pathologic features that
      drive gas exchange abnormalities in experimental HPS. Our recent studies have
      identified biliary epithelium and activation and interaction between the
      endothelin-1 (ET-1)/endothelial endothelin B (ETB) receptor and CX3CL1/CX3CR1
      pathways as important mechanisms for the observed pathologic events. These
      studies define novel interactions between the lung and liver in cirrhosis and may
      lead to effective medical therapies. 

PMID- 23874035
TI  - Promoting interdisciplinary research in departments of medicine: results from two
      models at Boston University School of Medicine.
AB  - We have sought to broaden our department's research capacity using two different
      interdisciplinary approaches. First, we created the Evans Center for
      Interdisciplinary Biomedical Research (ECIBR) - a virtual center that promotes
      and funds Affinity Research Collaboratives (ARCs) initiated by faculty from
      within and outside Boston University (BU). Of the 11 funded ARCs, the 4 ARCs in
      existence for a minimum of 3 years have a total of 37 participants, 93 co
      authored publications, and 33 new grants. Second, the Department of Medicine
      (DOM) created a Section of Computational Biomedicine in 2009 to enhance
      analytical and computational expertise in the DOM. After 3 years, the section is
      comprised of 10 faculty members and 21 trainees. The faculty members have
      collaborated with 20 faculty members in other sections or departments and secured
      12 extramural grants (totaling ~$20 million in direct costs). The ECIBR and the
      Section of Computational Biomedicine represent new organizational approaches to
      stimulating innovation in research in a DOM. 

PMID- 23874034
TI  - Deworming the world.
AB  - Worms or helminths have historically infected more than half the world's
      population, but were largely neglected by medical science and public health
      interventions because they were considered non-fatal and of minimal clinical
      significance. During the 1980s, several oral drugs that were originally developed
      for veterinary use were discovered to cure, in a single dose, most human helminth
      infections. This allowed the first systematic population-based studies of the
      morbid sequelae of chronic worm infection and their potential reversibility after
      treatment. Based on these studies, we now know that almost all infected children
      and many adults, particularly pregnant and lactating women, suffer adverse
      effects from worms, including growth stunting, anemia, decreased cognitive
      development, and poor birth outcomes as well as poor school and work performance.
      Worm-infected people also respond less well to vaccinations and are more
      susceptible to several co-conditions such as HIV and cirrhosis. Based on these
      findings, several vertically organized national control programs were initiated
      in developing countries against schistosomiasis and the soil-transmitted
      helminths (hookworm, ascariasis, and whipworm). In 2005, the impact of helminth
      infections was redefined in terms of disability-adjusted life years (DALYs). All
      worm infections amenable to population-based mass chemotherapy are thought today
      to cause 30 million DALYs worldwide or very close to the worldwide impact of
      tuberculosis (TB) or malaria. In addition, almost all worm-induced DALYs are
      potentially reversible or preventable with periodic treatment. In 2001, the World
      Health Assembly advocated for mass deworming to reach 75% of the at-risk school
      aged children of the world, but by 2011 only 13% had been reached. The recent
      large donations of anti-helminth drugs by major pharmaceutical companies linked
      to the inclusion of the "neglected tropical diseases" into current priorities for
      AIDS/TB and malaria now represent the best hope for closing this gap. 

PMID- 23874036
TI  - Community-acquired pneumonia: 2012 history, mythology, and science.
AB  - Pneumonia remains one of the major disease entities practicing physicians must
      manage. It is a leading cause of infection-related morbidity and mortality in all
      age groups, and a leading cause of death in those older than 65 years of age.
      Despite its frequency and importance, clinical questions have remained in the
      therapy of community-acquired pneumonia including when to start antibiotics, when
      to stop them, who to treat, and what agents to use. Answers to these questions
      have involved historical practice, mythology, and science-sometimes good science,
      and sometimes better science. How clinical decisions are made for patients with
      community-acquired pneumonia serves as an illustrative model for other problem
      areas of medicine and allows for insight as to how clinical decisions have been
      made and clinical practice established. 

PMID- 23874053
TI  - Coordination Chemistry of Disilylated Germylenes with Group 4 Metallocenes.
AB  - Reaction of the PEt3 adduct of a disilylated five-membered cyclic germylene with
      group 4 metallocene dichlorides in the presence of magnesium led to the formation
      of the respective germylene metallocene phosphine complexes of titanium,
      zirconium, and hafnium. Attempts to react the related NHC adduct of a disilylated
      four-membered cyclic germylene under the same conditions with Cp2TiCl2 did not
      give the expected germylene NHC titanocene complex. This complex was, however,
      obtained in the reaction of Cp2Ti(btmsa) with the NHC germylene adduct. A
      computational analysis of the structure of the group 4 metallocene germylene
      complexes revealed the multiple-bond character of the M-Ge(II) linkage, which can
      be rationalized with the classical sigma-donor/pi-acceptor interaction. The
      strength of the M-Ge(II) bond increases descending group 4.

PMID- 23874054
TI  - Cyclic Disilylated and Digermylated Germylenes.
AB  - The preparation of triethylphosphine adducts of cyclic disilylated or
      digermylated germylenes was achieved by reaction of 1,4-dipotassio-1,1,4,4
      tetrakis(trimethylsilyl)tetramethyltetrasilane with GeBr2.(dioxane) and PEt3.
      Phosphine abstraction with B(C6F5)3 allowed formation of the base-free
      germylenes, which undergo 1,2-trimethylsilyl shifts to the germylene atom to form
      the respective silagermene or digermene, which further dimerize in [2 + 2]
      cycloadditions to tricyclic compounds. The reasons responsible for the
      germylenes' completely different reactivities in comparison to the previously
      studied analogous stannylenes and plumbylenes were elucidated in a theoretical
      study.

PMID- 23874055
TI  - Conceptualizing and Validating Marital Quality in Beijing: A Pilot Study.
AB  - Since the inception of the economic reform, marital relationship in urban China
      has undergone dramatic transformations. Though the burgeoning body of scholarly
      research has demonstrated that marital quality has increasingly become an
      important aspect of family life among married persons in urban China, both the
      conceptualization and measurement of marital quality remain underdeveloped. The
      purpose of this pilot study is to develop and validate a comprehensive and
      culturally appropriate marital quality scale, namely the Chinese Marital Quality
      Scale (CMQS). Results from the confirmatory factor analysis (CFA) conducted on a
      sample of 387 married persons from Beijing indicate that the CMQS can be
      conceptualized as a two-factorial and multidimensional construct, encompassing
      marital happiness, marital interaction, marital disagreement, marital problem,
      and marital instability. Additional statistical analyses also indicate that the
      CMQS has exhibited satisfactory reliability and concurrent validity. It is thus
      concluded that the CMQS is a reliable and valid instrument to measure marital
      quality in contemporary Beijing and possibly in other Chinese cities.

PMID- 23874056
TI  - Impact of Competing Values and Choices on Democratic Support in Hong Kong.
AB  - This paper examines the reasons for the relatively low democratic support (DS) in
      Hong Kong in the context of competing values and choices based on the previous
      Asian Barometer Surveys. In so doing, it establishes a three-factor theoretical
      model that includes survey attitudinal statements related to authoritarianism
      (AU), nationalism (NA) and economic evaluations (EC) on DS. Using confirmatory
      factor analysis (CFA), the analysis shows that the hypothesized model is a very
      good fit. The Hong Kong people's relatively low DS, in terms of their
      unconditional support for democracy and the degree of democracy they want for
      Hong Kong, can be well explained by the three factors in combination. The factors
      have various extent of impact on DS, with AU being the strongest, followed by EC,
      and then NA. The paper contributes by illustrating the usefulness of CFA in
      political values research, unraveling the comparative importance of the values
      and choices in affecting DS, and establishing a model for further testing.

PMID- 23874057
TI  - The Multidimensionality of Welfare State Attitudes: A European Cross-National
      Study.
AB  - When evaluating the various aspects of the welfare state, people assess some
      aspects more positively than others. Following a multidimensional approach, this
      study systematically argues for a framework composed of seven dimensions of the
      welfare state, which are subject to the opinions of the public. Using
      confirmatory factor analyses, this conceptual framework of multidimensional
      welfare attitudes was tested on cross-national data from 22 countries
      participating in the 2008 European Social Survey. According to our empirical
      analysis, attitudes towards the welfare state are multidimensional; in general,
      people are very positive about the welfare state's goals and range, while
      simultaneously being critical of its efficiency, effectiveness and policy
      outcomes. We found that these dimensions relate to each other differently in
      different countries. Eastern/Southern Europeans combine a positive attitude
      towards the goals and role of government with a more critical attitude towards
      the welfare state's efficiency and policy outcomes. In contrast, Western/Northern
      Europeans' attitudes towards the various welfare state dimensions are based
      partly on a fundamentally positive or negative stance towards the welfare state.

PMID- 23874058
TI  - Ageing, Leisure, and Social Connectedness: How could Leisure Help Reduce Social
      Isolation of Older People?
AB  - This study investigates the relation between leisure activities and the social
      status of the elderly based on a heterogeneous sample of the Dutch population.
      Close relationships are also analyzed to identify which people could serve as
      successful stimulators of leisure participation. The social profile confirms that
      older people have fewer social contacts and often feel lonely. This study shows
      that leisure activities explain a significant part of older people's social
      connectedness. Voluntary work, cultural activities, holiday, sports, reading
      books, hobbies and shopping are found to be successful predictors for social
      connectedness of older people. Watching TV, listening to the radio, and spending
      time behind the computer (passive activities) were not associated with social
      connectedness. Friends correlate positively to participation in leisure
      activities. Partners play a role in participation in cultural activities and
      sports; parents play a role in participation in voluntary work and holidays;
      siblings play a role in voluntary work and sports; and children play a role in
      cultural activities, reading books, and shopping. Local communities can use these
      close relationships and develop special programs to increase social connectedness
      and hence improve quality of life for older adults.

PMID- 23874059
TI  - The Importance of General Self-Efficacy for the Quality of Life of Adolescents
      with Chronic Conditions.
AB  - We investigated the influence of general self-efficacy perceived by adolescents
      with chronic conditions and parents on quality of life. This cross-sectional
      study used the general self-efficacy scale and DISABKIDS condition-generic module
      to survey adolescents (92/293; 31 %) with type I diabetes, juvenile rheumatoid
      arthritis, cystic fibrosis, kidney/urological conditions, and neuromuscular
      disorders; and parents (121/293; 41 %). Self perceived and parents' perceived
      general self-efficacy of adolescents was compared using paired t-tests, and
      adolescents' quality of life and general self-efficacy were compared among
      conditions using analysis of variance. Bivariate correlations between general
      self-efficacy and quality of life were identified, and multiple regression sought
      predictors of quality of life after controlling for background variables. Social
      quality of life was lowest among those with neuromuscular disorders. General self
      efficacy was highest among adolescents with cystic fibrosis and lowest among
      those with urological conditions. Parents' perceptions of general self-efficacy
      were higher than adolescents' (p <= 0.05), although absolute differences were
      small. General self-efficacy perceived by parents and adolescents was related to
      emotional, physical, and social quality of life. Adolescents' perceived self
      efficacy predicted all quality of life domains. Parents' perceptions of the
      adolescents self-efficacy predicted the adolescents' social quality of life (beta
      = 0.19; p <= 0.01). General self-efficacy of adolescents with chronic conditions
      as perceived by themselves and their parents is important for adolescents'
      quality of life. Interventions to improve general self-efficacy should benefit
      quality of life among these adolescents.

PMID- 23874060
TI  - Estimation with Right-Censored Observations Under A Semi-Markov Model.
AB  - The semi-Markov process often provides a better framework than the classical
      Markov process for the analysis of events with multiple states. The purpose of
      this paper is twofold. First, we show that in the presence of right censoring,
      when the right end-point of the support of the censoring time is strictly less
      than the right end-point of the support of the semi-Markov kernel, the transition
      probability of the semi-Markov process is nonidentifiable, and the estimators
      proposed in the literature are inconsistent in general. We derive the set of all
      attainable values for the transition probability based on the censored data, and
      we propose a nonparametric inference procedure for the transition probability
      using this set. Second, the conventional approach to constructing confidence
      bands is not applicable for the semi-Markov kernel and the sojourn time
      distribution. We propose new perturbation resampling methods to construct these
      confidence bands. Different weights and transformations are explored in the
      construction. We use simulation to examine our proposals and illustrate them with
      hospitalization data from a recent cancer survivor study.

PMID- 23874061
TI  - The Relation Between Maternal and Child Depression in Mexican American Families.
AB  - In an effort to better understand possible pathways that lead to a relatively
      high incidence of depressive symptoms among Mexican American youth, an
      interpersonal stress model of depression was tested using a community sample of
      674 Mexican American mothers and their 5th grade children. Structural equation
      analyses revealed that maternal depression was positively related to mothers'
      interpersonal stress in their relationships. Additionally, maternal poor
      parenting quality was associated with three child outcomes: lower social
      competence, higher interpersonal stress, and higher depressive symptoms. Child
      difficulties with peers, however, were not related to child depression. Overall,
      evidence suggests that familial factors, rather than peer factors, were related
      to child depression for these study participants.

PMID- 23874062
TI  - Discussion of "Semiparametric Estimation of Treatment Effect in a Pretest
      Posttest Study With Missing Data" by Davidian, Tsiatis and Leon.

PMID- 23874063
TI  - Effects of astaxanthin on antioxidation in human aqueous humor.
AB  - We evaluated the antioxidative effects of astaxanthin through the changes in
      superoxide scavenging activity, levels of hydrogen peroxide and total
      hydroperoxides in human aqueous humor. The study subjects were 35 patients who
      underwent bilateral cataract surgery on one side before and the other side after
      intake of astaxanthin (6 mg/day for 2 weeks). Their aqueous humor was taken
      during the surgery and subjected to measurements of the three parameters. After
      astaxanthin intake, the superoxide scavenging activity was significantly (p<0.05)
      elevated, while the level of total hydroperoxides was significantly (p<0.05)
      lowered. There was a significant negative correlation between the superoxide
      scavenging activity and the level of total hydroperoxides (r = -0.485, p<0.01),
      but no correlations between the hydrogen peroxide level and the other two
      parameters. Astaxanthin intake clearly enhanced the superoxide scavenging
      activity and suppressed the total hydroperoxides production in human aqueous
      humor, indicating the possibility that astaxanthin has suppressive effects on
      various oxidative stress-related diseases. 

PMID- 23874064
TI  - Repeated short-term daily exercise ameliorates oxidative cerebral damage and the
      resultant motor dysfunction after transient ischemia in rats.
AB  - Long-term exercise prior to brain ischemia enhances the activities of antioxidant
      enzymes and leads to a significant reduction in brain damage and neurological
      deficits in rats subjected to transient middle cerebral artery occlusion.
      However, it has not been established whether relatively short-term exercise
      generates similar results following middle cerebral artery occlusion. We aimed to
      determine whether short-term exercise could reduce oxidative damage and prevent
      sensori-motor dysfunction. Male Wistar rats were subjected to perform daily
      exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed
      by a 90-min middle cerebral artery occlusion. Animals were assessed after middle
      cerebral artery occlusion for neurological deficits and sensori-motor function.
      Brain tissues were processed to evaluate infarct volume and oxidative damage.
      Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal
      modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were
      evaluated using immunohistochemistry for thioredoxin and activity assay for
      superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis
      and impairment in forelimb motor coordination. Furthermore, exercise had effect
      on superoxide dismutase and reduced the infarct volume and the number of cells
      immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'
      deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for
      3 weeks is useful for ameliorating ischemia-induced brain injury. 

PMID- 23874065
TI  - Polymorphisms in genes encoding antioxidant enzymes (SOD2, CAT, GPx, TXNRD,
      SEPP1, SEP15 and SELS) and risk of chronic kidney disease in Japanese - cross
      sectional data from the J-MICC study.
AB  - Chronic kidney disease (CKD) is well known as a strong risk factor for both of
      end-stage renal disease and cardiovascular disease. To clarify the association of
      polymorphisms in the genes encoding antioxidant enzymes (SOD2, CAT, GPx, TXNRD,
      SEPP1, SEP15 and SELS) with the risk of CKD in Japanese, we examined this
      association using the cross-sectional data of Japan Multi-Institutional
      Collaborative Cohort (J-MICC) Study. The subjects were 3,285 men and women, aged
      35-69 years, selected from J-MICC Study participants for whom genotyping were
      conducted by multiplex polymerase chain reaction-based Invader assay. The
      prevalence of CKD was determined for CKD stages 3-5 (eGFR <60 ml/min/1.73 m(2)).
      When those with CAT C-262T C/C were defined as reference, those with CAT C-262T
      C/T demonstrated the OR for CKD of 0.67 (95% CI 0.43-1.06) with the marginally
      significant trend for decreased odds ratio with increasing numbers of T allele (p
      = 0.070). There were no significant associations between the other polymorphisms
      with CKD risk. The present study found a marginally significant trend of the
      decreased risk of CKD with increasing numbers of T allele of CAT, which may
      suggest the possibility of personalized risk estimation of this life-limiting
      disease in the near future. 

PMID- 23874066
TI  - Apoptotic effect of tolfenamic acid on MDA-MB-231 breast cancer cells and
      xenograft tumors.
AB  - Recent studies have indicated that non-steroidal anti-inflammatory drug (NSAID),
      particularly tolfenamic acid, can inhibit proliferation and induce apoptosis
      invarious cancer cells. Breast cancer represents one-third of all cancers
      diagnosed in women and is the second leading cause of cancer death in Western
      European and North American women. In the present study, we investigated the
      apoptotic effect of tolfenamic acid in MDA-MB-231 estrogen receptor-negative
      human breast carcinoma cells and in a xenograft tumor model. Treatment of cells
      with tolfenamic acid significantly decreased cell viability in a concentration
      dependent manner. Notably, tolfenamic acid increased apoptosis-related proteins,
      such as p53 and p21, within 48 h. Furthermore, in vivo experiments showed that
      tolfenamic acid treatment resulted in a significant reduction in tumor volume
      over 5 weeks. Immunohistochemistry results showed that apoptosis-related protein
      induction by tolfenamic acid was significantly higher in the 50 mg/kg-treated
      group compared to the control group. Together, these results indicate that
      tolfenamic acid induces apoptosis in MDA-MB-231 breast cancer cells and tumor
      xenograft model and it may be a potential chemotherapeutic agent against breast
      cancer. 

PMID- 23874067
TI  - Evaluation of two distinct methods to quantify the uptake of crocidolite fibers
      by mesothelial cells.
AB  - Exposure to asbestos fibers increases the risk of mesothelioma in humans. One
      hypothetical carcinogenic mechanism is that asbestos fibers may directly induce
      mutations in mesothelial cells. Although the uptake of asbestos fibers by
      mesothelial cells is recognized, methods for the quantification of the uptake
      have not been well established. In the present study, we evaluated two distinct
      methods, using crocidolite fibers and MeT5A mesothelial cells. One method is
      histological evaluation using the cell-block technique, which allows for the
      direct cross-sectional observation of cells and fibers. We found the bright field
      observation with *1000 magnification (oil-immersion) of the sample with
      Kernechtrot staining was most suitable for this purpose. The other method is flow
      cytometric analysis, which permits the evaluation of a much larger number of
      cells. We observed that the side scatter (SSC) increased with the intracellular
      fibers, and that the "mean SSC ratio (treated/control)" was useful for
      quantification. We could collect the cells with abundant internalized crocidolite
      fibers by sorting. Results of the two methodologies were correlated well in the
      experiments. The quantities of internalized fibers increased with incubation time
      and loaded dosage, but they were inversely associated with cellular density in
      culture. 

PMID- 23874068
TI  - Effect of omega-3 and ascorbic acid on inflammation markers in depressed shift
      workers in Shahid Tondgoyan Oil Refinery, Iran: a randomized double-blind placebo
      controlled study.
AB  - The present study aimed to assess the effect of supplementation of omega-3 and/or
      vitamin C on serum interleukin-6 and high sensitivity C-reactive protein
      concentration and depression scores among shift workers in Shahid Tondgoyan oil
      refinery. The study design was randomized, double-blind, placebo-controlled,
      parallel trial. Totally 136 shift workers with a depression score >=10 in 21-item
      Beck Depression Rating Scale were randomly assigned to receive omega-3 (180 mg
      eicosapentaenoate acid and 120 mg docosahexaenoic acid) or/and vitamin C 250 mg
      or placebo twice daily (with the same taste and shape as omega-3 and vitamin C)
      for 60 days in four groups. Depression score, interleukin-6 and high sensitivity
      C-reactive protein were measured at baseline and after 60 days. This study showed
      that supplementation of omega-3 plus vitamin C is associated with a decrease in
      depression score (p<0.05). Supplementation of omega-3 without vitamin C, is
      associated with a reduction in depression score (p<0.0001) and high sensitivity C
      reactive protein concentration (p<0.01). Therefore omega-3 supplementation showed
      a better effect on reducing depression score and high sensitivity C-reactive
      protein, but supplementation of vitamin C along with omega-3 did not have
      significant effect on change in C-reactive protein level compared to omega-3
      alone. ( REGISTRATION NUMBER: IRCT201202189056N1).

PMID- 23874069
TI  - Possible role of S-equol on bone loss via amelioration of inflammatory indices in
      ovariectomized mice.
AB  - S-equol is a natural metabolite of the soy isoflavone, daidzein, produced by
      intestinal bacteria. S-equol has been shown to have greater estrogenic activity
      than other soy isoflavones and prevent bone loss in post-menopausal women.
      Estrogen regulates both bone remodeling and hemopoiesis in the bone marrow, these
      processes that communicate closely with each other. In this study, we
      investigated the effect of S-equol on bone mass and gene expression of bone
      marrow cells in ovariectomized (OVX) mice. Female ddY strain mice, aged 12 weeks,
      were either sham operated or OVX. The OVX mice were randomly divided into two
      groups: (1) OVX control and (2) OVX fed a 0.06% (w/w) S-equol supplemented diet.
      After 2 weeks, the trabecular bone volume of the femoral distal metaphysis was
      markedly reduced in OVX mice. However, treatment with equol was observed to
      ameliorate this. Expression of inflammatory-, osteoclastogenesis- and
      adipogenesis-related genes was increased in OVX mice compared with sham mice, and
      equol was observed to suppress their expression. The present study demonstrates
      that equol might ameliorate bone loss caused by estrogen deficiency through
      regulating hemopoiesis and production of inflammatory cytokines in bone marrow
      cells. 

PMID- 23874070
TI  - Abnormalities in the serum phospholipids fatty acid profile in patients with
      alcoholic liver cirrhosis - a pilot study.
AB  - The fatty acid composition of serum phospholipids were analyzed in 20 patients
      with alcoholic liver cirrhosis (11 with malnutrition and 9 with acceptable
      nutritional status); 25 healthy age and sex-matched adults were used as controls.
      Cirrhotic patients showed higher levels of palmitic acid and total saturated
      fatty acids than healthy subjects. Total n-6 and n-3 polyunsaturated fatty acids
      (PUFA), and levels of linoleic, dihomo-gama linolenic, arachidonic, and
      docosahexaenoic acid were significantly lower (p<0.001) in patients with
      alcoholic cirrhosis compared to healthy controls. Significant changes were also
      found between patients stratified according to nutritional status. In particular,
      the sum of n-3 PUFA was significantly lower (p<0.001) and ratio of n-6/n-3 fatty
      acids was higher (p<0.01) in malnourished patients when compared to the patients
      with acceptable nutritional status. Furthermore, important changes in the levels
      of saturated fatty acids, palmitoleic and oleic acid and long-chain PUFA were
      found in well-nourished patients with alcoholic cirrhosis as well. Our present
      data confirmed evidence that malnutrition is one of the factors that led to lower
      levels of polyunsaturated fatty acids in patients with alcoholic liver cirrhosis.
      PUFA supplementation in the latter needs further investigation. 

PMID- 23874071
TI  - Nonsteroidal anti-inflammatory drug-induced visible and invisible small
      intestinal injury.
AB  - Permeation of the small intestinal mucosa is a key mechanism in the induction of
      enteropathy. We investigated the effect of rebamipide in healthy subjects with
      diclofenac-induced small intestinal damage and permeability. In this crossover
      study, each treatment period was 1 week with a 4-week washout period. Diclofenac
      (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo
      were administered. Capsule endoscopy and a sugar permeability test were performed
      on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small
      intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups.
      Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the
      initial dose during the first treatment period in the placebo group, and from
      0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal
      mucosal damage, the increased permeability in both groups resulted in sustained
      high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12%
      in the rebamipide group) through the 4-week washout period. Diclofenac
      administration induced enteropathy and hyperpermeability of the small intestine.
      The sustained hyperpermeability during the washout period may indicate the
      presence of invisible fragility. 

PMID- 23874072
TI  - Case-control study of association of eosinophilic gastrointestinal disorders with
      Helicobacter pylori infection in Japan.
AB  - Recent studies have suggested that decrease in Helicobacter pylori infection may
      predispose to allergic diseases. However, there are few reports of the
      relationships of eosinophilic gastrointestinal disorders (EGIDs), especially
      eosinophilic gastroenteritis (EGE), with H. pylori infection. We investigated the
      possible influence of H. pylori infection on EGIDs in Japanese patients. We
      performed a case-control study to investigate the prevalence of H. pylori
      infection in patients with EGIDs. Eighteen with eosinophilic esophagitis (EoE)
      and 22 with EGE were enrolled. For each patient, 3 age- and gender-matched normal
      controls (n = 120) were randomly selected from a population who received a
      medical check-up between April 2010 and December 2011 at the Shimane Institute of
      Health Science. The mean ages of the EoE and EGE patients were 50.9 +/- 17 and
      49.2 +/- 20 years, respectively. Males were more frequently seen in the EoE
      group, while there was no significant gender difference in regard to EGE. Of the
      patients with EoE, 22.3% were infected with H. pylori, as compared to 55.5% of
      their age- and sex-matched normal controls. The odds ratio for EoE patients to
      have an H. pylori infection was 0.22 (p<0.05). In addition, 22.7% of the patients
      with EGE and 48.5% of their matched controls were infected with H. pylori, with
      odds ratio for EGE patients to have an H. pylori infection shown to be 0.31
      (p<0.05). In conclusion, the prevalence of H. pylori infection was significantly
      lower in EGE and EoE patients in Japan as compared to normal control subjects. 

PMID- 23874073
TI  - A randomized, double-blind, sham-controlled study of static electric field
      therapy by high voltage alternating current for active rheumatoid arthritis.
AB  - Static electric field therapy by high voltage alternating current (EF-HVAC) is a
      traditional complementary Japanese medicine used for headache, shoulder
      stiffness, chronic constipation and insomnia. Open-label studies and clinical
      experience in Japan have suggested that this electric field therapy is safe and
      effective in treating chronic arthritis. We evaluated the efficacy of EF-HVAC
      therapy in a randomized, double-blinded, sham-controlled trial in patients with
      active rheumatoid arthritis (RA) in community-based general physician centers.
      Thirty patients fulfilling American College of Rheumatology (ACR) criteria for RA
      were treated with EF-HVAC therapy with the LEGACIS PLUS System (COCOROCA Corp.,
      Tokyo, Japan) or sham therapy for 12 weeks and followed for 4 weeks without
      treatment. The disease activity score 28 (DAS28-CRP), visual analogue scale for
      pain (VAS), modified health assessment questionnaire (MHAQ), and inflammatory
      parameters were used as the outcome variable. Twenty four patients (n = 12 in
      each group) were analyzed by a per protocol analysis. Although a significant
      reduction in DAS28-CRP was observed in EF-HVAC group at 8 and 12 weeks compared
      to before treatment, there were no significant differences in DAS28-CRP scores
      during treatment between two groups. The scale of VAS was also significantly
      decreased by the treatment with EF-HVAC compared to before treatment, in
      addition, the scale of VAS in EF-HVAC group was significantly lower than sham
      group at 8 and 12 weeks. Changes in another parameters including MHAQ were not
      significant between before and after treatment, or by all comparative study
      between two groups. There were no adverse events related the treatment. In
      conclusion, the EF-HVAC therapy has a beneficial effect on the improvement to
      subjective pain of RA. 

PMID- 23874074
TI  - Effects of liraglutide on postprandial insulin and glucagon responses in Japanese
      patients with type 2 diabetes.
AB  - This study assessed the endocrine pancreatic responses to liraglutide (0.9 mg
      once a day) during normal living conditions in Japanese patients with type 2
      diabetes. The study included 14 hospitalized patients with type 2 diabetes. Meal
      tests were performed after improvement of glycemic control achieved by two weeks
      of multiple insulin injection therapy and after approximately two weeks of
      liraglutide treatment. Continuous glucose monitoring was performed to compare
      daily variation in glycemic control between multiple insulin injection therapy
      and liraglutide treatment. Liraglutide reduced plasma glucose levels after the
      test meals (60-180 min; p<0.05), as a result of significant increases in insulin
      secretion (0-180 min; p<0.05) and decreases in the incremental ratio of plasma
      glucagon (15-60 min; p<0.05). Continuous glucose monitoring showed that
      liraglutide treatment was also associated with a decrease in glucose variability.
      We also demonstrated that optimal glycemic control seen as a reduction in 24-h
      mean glucose levels and variability was obtained only with liraglutide
      monotherapy. In conclusion, liraglutide treatment increases insulin secretion and
      suppresses glucagon secretion in Japanese patients with type 2 diabetes under
      normal living conditions. The main therapeutic advantages of liraglutide are its
      use as monotherapy and its ability to decrease glucose variability. 

PMID- 23874076
TI  - Evaluation of dihydrooroidin as an antifouling additive in marine paint.
AB  - Methods used to deter biofouling of underwater structures and marine vessels
      present a serious environmental issue and are both problematic and costly for
      government and commercial marine vessels worldwide. Current antifouling methods
      include compounds that are toxic to aquatic wildlife and marine ecosystems.
      Dihydrooroidin (DHO) was shown to completely inhibit Halomonas pacifica biofilms
      at 100 MUM in a static biofilm inhibition assay giving precedence for the
      inhibition of other marine-biofilm-forming organisms. Herein we present DHO as an
      effective paint-based, non-cytotoxic, antifouling agent against marine biofouling
      processes in a marine mesocosm.

PMID- 23874077
TI  - Comparison of DLK incidence after laser in situ keratomileusis associated with
      two femtosecond lasers: Femto LDV and IntraLase FS60.
AB  - PURPOSE: To compare the incidence of diffuse lamellar keratitis (DLK) after laser
      in situ keratomileusis (LASIK) with flap creation using the Femto LDV and
      IntraLaseTM FS60 femtosecond lasers.0. METHODS: A total of 818 consecutive myopic
      eyes had LASIK performed using either Femto LDV or IntraLase FS60 for flap
      creation. The same excimer laser, the Allegretto Wave(r) Eye-Q Laser, was used
      for correcting refractive errors for all patients. In the preoperative
      examination, uncorrected distance visual acuity, corrected distance visual
      acuity, and manifest refraction spherical equivalent were measured. At the postop
      examination, the same examinations were performed along with a slit-lamp
      biomicroscopic examination, and patients with DLK were classified into stages.
      For the statistical analysis of the DLK occurrence rate and the visual and
      refractive outcomes, the Mann-Whitney's U-test was used. RESULTS: In the Femto
      LDV group with 514 eyes, 42 (8.17%) had DLK. In the IntraLase FS60 group with 304
      eyes, 114 (37.5%) had DLK. There was a statistically significant difference in
      the DLK incidence rate between these groups (P < 0.0001). Both groups had
      excellent visual and refractive outcomes. Although low levels of DLK were
      observed for both groups, they did not affect visual acuity. CONCLUSION: While
      there were significantly fewer incidences of low level DLK when using Femto LDV,
      neither femtosecond laser induced high levels of DLK, and any postoperative DLK
      cleared up within 1 week. Therefore, both lasers provide excellent results, with
      no clinical differences, and both excel at flap creation for LASIK.

PMID- 23874078
TI  - Pattern of presentation of idiopathic polypoidal choroidal vasculopathy in
      Ibadan, Sub-Saharan Africa.
AB  - BACKGROUND: Idiopathic polypoidal choroidal vasculopathy is an abnormal choroidal
      vascular pathology similar to age-related macular degeneration. It may present
      with sudden visual loss from hemorrhagic retinal pigment epithelial detachment
      and breakthrough vitreous hemorrhage or with chronic recurrent episodes. The
      condition is not uncommon in the retina clinic at the University College
      Hospital, Ibadan, Sub-Saharan Africa. This study presents the pattern of
      presentation in Ibadan. METHODS: We review all cases of idiopathic polypoidal
      choroidal vasculopathy seen from 2007 to 2012 in the retina clinic at the
      University College Hospital, Ibadan, to determine the major pattern of
      presentations, available treatment modalities, and visual outcomes. RESULTS: Ten
      cases were seen during the study period. Their mean age was 58 years, with a male
      to female ratio of 1:4. The most common presenting complaint was sudden visual
      loss. Major examination findings were retinal pigment epithelial detachment,
      orange subretinal lesions, and breakthrough vitreous hemorrhage. The modalities
      of treatment available included vitrectomy to clear vitreous hemorrhage.
      Intravitreal bevacizumab reduced the height of the pigment epithelial detachment
      and cleared vitreous hemorrhage. Thermal laser was applied for extrafoveal
      lesions. Two patients with subfoveal lesions were referred abroad for
      photodynamic therapy. Visual outcome showed significant improvement in
      vitrectomized patients who presented with vitreous hemorrhage. Presenting vision
      of hand motion and light perception improved to vision ranging from counting
      fingers to 6/12 after vitrectomy. CONCLUSION: Idiopathic polypoidal choroidal
      vasculopathy may not be uncommon in Sub-Saharan Africa. A high index of suspicion
      is warranted in the diagnosis so as to provide timely intervention.

PMID- 23874079
TI  - Comparing bevacizumab and ranibizumab for initial reduction of central macular
      thickness in patients with retinal vein occlusions.
AB  - PURPOSE: To examine short-term effects of ranibizumab versus bevacizumab on
      reduction of optical coherence tomography (OCT) central macular thickness (CMT)
      in patients with macular edema secondary to retinal vein occlusions (RVOs).
      METHODS: This is a retrospective analysis in which patients with RVOs were
      injected with either bevacizumab or ranibizumab. At 2 weeks, all patients were
      injected with a dexamethasone intravitreal implant (Ozurdex(r)). CMT on OCT and
      best-corrected visual acuity were obtained at baseline, at 2 weeks (just prior to
      the dexamethasone intravitreal implant), and 6 weeks. RESULTS: Sixty-four
      patients received injections (32 bevacizumab; 32 ranibizumab). At 2 weeks,
      bevacizumab group had a mean (+/-standard error of mean [SEM]) CMT reduction of
      26.2% +/- 3.4% versus 47% +/- 3.5% reduction with ranibizumab (P < 0.0001). At 6
      weeks, there was a 31.6% +/- 3.2% CMT reduction with bevacizumab versus 52% +/-
      3.2% with ranibizumab (P < 0.0001). At 2 weeks, 15 (9%) of bevacizumab patients
      versus 25 (78.1%) ranibizumab patients achieved OCT CMT < 300 MUm (P = 0.0192).
      At 6 weeks, 18 (56.3%) of bevacizumab compared to 30 (93.8%) of ranibizumab
      patients achieved CMT < 300 MUm (P = 0.0010). Visual acuity was not significantly
      different at each time interval between the groups. CONCLUSION: Ranibizumab
      appears to have a greater effect in the short-term of decreasing macular edema on
      OCT when compared to bevacizumab in patients with RVOs.

PMID- 23874080
TI  - Assessment of vitreous drug concentration in the porcine eye following
      intracameral injection or irrigation with moxifloxacin.
AB  - INTRODUCTION: Posterior capsule rupture causes instant vitreous contamination,
      resulting in endophthalmitis. However, transfer of intracameral moxifloxacin
      (MFLX) to the vitreous has not been examined in detail. We investigated vitreous
      antibiotic concentrations following intracameral MFLX in both ruptured and intact
      posterior capsular eyes. METHODS: Experiment 1: Intraocular lenses were inserted
      into 21 extracted porcine eyes by one of the following three methods: (1)
      Irrigation: Throughout surgery, 33-fold diluted MFLX irrigation solution (150
      MUg/mL) was used; (2) Bag and chamber flushing: After surgery, the anterior
      chamber and area behind the intraocular lenses were irrigated with 30-fold
      diluted MFLX (167 MUg/mL) using a 5 mL syringe; (3) Simple injection: Tenfold
      diluted MFLX (50 MUg in 0.1 mL) was injected intracamerally at the conclusion of
      surgery. The eyeballs were frozen and the anterior, central, and posterior
      portions of the vitreous were cubed. After defrosting, concentrations were
      measured using high-performance liquid chromatography. Experiment 2: The same
      procedure was conducted for 18 eyes in which the posterior capsule had been
      ruptured. RESULTS: Experiment 1: Transfer of intracameral MFLX to the anterior
      vitreous was approximately 1% (1.56-2.20 MUg/mL) regardless of the administration
      method. Experiment 2: MFLX reached a high concentration in the vitreous with
      irrigation solution administration (maximum 30.22 MUg/mL). The concentrations
      reached by simple injection or flushing were significantly less than those
      obtained by irrigation. CONCLUSION: With an intact posterior capsule,
      intracameral MFLX exhibited limited effects on vitreous concentration. Despite
      the fact that the risk of infection clearly increases in cases of ruptured
      capsule, no special infection prevention protocol has been proposed. It was
      confirmed that irrigation solution caused vitreous contamination in ruptured eyes
      within only a short irrigation time. In this case, intracameral administration
      did not necessarily achieve preventive concentrations for endophthalmitis, but it
      appears that an effective drug concentration can be achieved in the vitreous by
      the administration of irrigation solution.

PMID- 23874081
TI  - Assessment of the tolerability profile of an ophthalmic solution of 5%
      glycyrrhizin and copolymer PEG/PPG on healthy volunteers and evaluation of its
      efficacy in the treatment of moderate to severe blepharitis.
AB  - PURPOSE: To evaluate the tolerability on healthy volunteers and the efficacy on
      subjects affected by chronic moderate/severe blepharitis of a 5% glycyrrhizin and
      copolymer poly(ethylene glycol)/poly(propylene glycol)(PEG/PPG) ophthalmic
      solution. METHODS: The study was a randomized, controlled, open label, intra
      patient monocentric study. It consisted of two different phases, the assessment
      of tolerability phase on 20 healthy volunteers, and the evaluation of the
      efficacy on 21 subjects affected by chronic moderate/severe blepharitis; the
      treatment period was 2 weeks, followed by 1-week of follow-up. In the efficacy
      phase, in both eyes, eyelid hygiene was also performed. At day 0, 3, 7, 14, and
      21 a complete ophthalmological examination was performed. In the tolerability
      phase, signs of clinical toxicity were recorded and subject-reported symptoms
      were collected using a questionnaire. In the efficacy phase, global signs and
      symptoms of blepharitis scores were collected using standardized photographic
      scales and questionnaire. The statistical analysis was performed using the
      Wilcoxon signed-rank test. RESULTS: No ocular signs of drug toxicity were
      reported. During the treatment period for tolerability phase, there were
      statistically significant higher scores of tearing and ocular discomfort in the
      tolerability study group versus the tolerability control group. In the efficacy
      phase, differences between global scores of the two groups were statistically
      significant at day 0 (score of the efficacy study group was higher than the
      efficacy control group; P = 0.005) and at day 21 (score of the efficacy study
      group was lower than the efficacy control group (P <= 0.001).The difference of
      global scores at day 3, 7, 14, and 21 versus day 0 was statistically significant
      in both groups. No serious adverse events occurred. CONCLUSION: The 5%
      glycyrrhizin ophthalmic solution was well tolerated in healthy volunteers and in
      patients with chronic moderate/severe blepharitis, and in association with eyelid
      hygiene showed good clinical anti-inflammatory activity that lasted after
      instillation suspension.

PMID- 23874082
TI  - Effects of tafluprost treatment for 3 years in patients with normal-tension
      glaucoma.
AB  - PURPOSE: To evaluate the effects of tafluprost treatment for 3 years on
      intraocular pressure (IOP) and visual field performance. METHODS: The IOP of 55
      patients with normal-tension glaucoma was monitored every 1-3 months for 3 years.
      The Humphrey visual field test was performed every 6 months after treatment and
      results compared with before-treatment results. Visual field performance was also
      evaluated by trend and event analysis. RESULTS: After 3 years' tafluprost single
      use vials treatment, the IOP (12.8 +/- 2.8 mmHg [mean +/- standard deviation])
      was significantly lower than before treatment (15.7 +/- 2.2 mmHg; P < 0.0001).
      When comparing before-treatment Humphrey visual field test findings with those
      after 3 years of treatment, no change was found in the mean deviation and pattern
      standard deviation. Visual field performance had worsened in four patients and
      three patients according to trend analysis and event analysis, respectively.
      Adverse reactions appeared in ten cases and one patient (1.8%) discontinued
      treatment due to an adverse reaction. CONCLUSION: Tafluprost single-use vials
      treatment was effective in reducing IOP over the 3 years of this study, but
      visual field performance worsened by 10.3%-13.8% in patients with normal-tension
      glaucoma. Safety was satisfactory.

PMID- 23874083
TI  - Risk factors for choroidal detachment after trabeculectomy with mitomycin C.
AB  - PURPOSE: To evaluate the risk factors for choroidal detachment after
      trabeculectomy with mitomycin C (MMC). MATERIALS AND METHODS: We retrospectively
      evaluated 420 patients (420 eyes) with glaucoma who underwent trabeculectomy with
      MMC between June 1, 2005 and December 31, 2010 at Kumamoto University Hospital,
      Japan. Choroidal detachment after trabeculectomy was defined as a solid-appearing
      elevation of the retina and choroid. Logistic multivariable analysis was applied
      to determine the risk factors for choroidal detachment. The following factors
      were assessed: gender, age, subtypes of glaucoma, eye laterality, history of
      previous cataract surgery, preoperative intraocular pressure (IOP; mean of three
      Goldmann applanation readings recorded on different days), postoperative IOP
      (mean of seven Goldmann applanation readings recorded on 7 consecutive days after
      trabeculectomy), and postoperative laser suture lysis. RESULTS: Of the 420
      patients, 79 (18.8%) revealed choroidal detachments. The mean period between
      trabeculectomy and choroidal detachment was 6.1 +/- 3.6 days. The mean IOP at the
      time of the choroidal detachment was 5.5 +/- 3.6 mmHg. Age (odds ratio [OR] =
      1.028/year, P = 0.0068) and postoperative IOP (OR = 0.887/mmHg, P < 0.0001) were
      risk factors for choroidal detachment after trabeculectomy. The subgroup analysis
      for eyes with open angle glaucoma (201 patients) revealed that age (OR =
      1.060/year, P = 0.0040) and postoperative IOP (OR = 0.898/mmHg, P = 0.0110) were
      significant risk factors for choroidal detachment after trabeculectomy with MMC.
      CONCLUSION: Among glaucoma patients, older age and lower postoperative IOP are
      risk factors for choroidal detachment after trabeculectomy with MMC. In eyes with
      open angle glaucoma, older age and lower postoperative IOP are risk factors for
      choroidal detachment after trabeculectomy with MMC.

PMID- 23874084
TI  - Effect of ranibizumab on serous and vascular pigment epithelial detachments
      associated with exudative age-related macular degeneration.
AB  - PURPOSE: To report the effect of intravitreal ranibizumab therapy for serous and
      vascular pigment epithelial detachments (PED) associated with choroidal
      neovascularisation (CNV) secondary to age-related macular degeneration (AMD).
      METHODS: In a prospective study, best-corrected visual acuity (BCVA) and optical
      coherence tomography (OCT) data were collected for 62 eyes of 62 patients, with
      serous or vascular PED associated with CNV secondary to AMD. Intravitreal
      ranibizumab 0.5 mg was administered with a loading phase of three consecutive
      monthly injections, followed by monthly review with further treatment, as
      indicated according to the retreatment criteria of the PrONTO study. The change
      in visual acuity and PED height from baseline to month 12 after the first
      injection was determined. RESULTS: Sixty-one eyes of 61 patients (one of the
      patients developed retinal pigment epithelial tear and was excluded from the
      study) were assessed at the 12-month follow-up examination. There were two types
      of PED, including vascular PED in 32 patients (Group A) and serous PED (Group B)
      in 29 patients. The mean improvement of mean BCVA from baseline to 12 months was
      0.09 logMAR (Logarithm of the Minimum Angle of Resolution) in Group A and 0.13
      logMAR in Group B. Both groups showed significant improvement of the mean BCVA 12
      months after the first injection compared with the baseline value (P < 0.05). In
      relation to the PED height, the mean decrease of mean PED height from baseline to
      12 months was 135 MUm in Group A and 180 MUm in Group B. Both groups showed
      significant reduction of the PED height during the follow-up period (P < 0.01).
      The PED anatomical response to ranibizumab was not correlated with the BCVA
      improvement in any of the groups. Apart from one patient who developed pigment
      epithelial tear no other complications were documented. CONCLUSION: Ranibizumab
      is an effective and safe treatment for improving vision in patients with serous
      and vascular PED, although the anatomical response of the PED to ranibizumab may
      not correlate directly with the visual outcome.

PMID- 23874085
TI  - Comparison of autofluorescence imaging bronchoscopy and white light bronchoscopy
      for detection of lung cancers and precancerous lesions.
AB  - BACKGROUND: The purpose of this paper was to compare the sensitivity,
      specificity, and overall diagnostic performance of autofluorescence imaging
      bronchoscopy (AFI) versus white light bronchoscopy (WLB) in the detection of lung
      cancers and precancerous lesions by meta-analysis. METHODS: We performed a
      literature search using the PubMed and EMBASE databases to identify studies
      published between March 1991 and March 2012. Article selection, quality
      assessment, and data extraction were then performed. The pooled sensitivity,
      specificity, diagnostic odds ratio, and area under the curve of the summary
      receiver operating characteristic for AFI versus WLB were calculated using Stata
      version 12.0 software. RESULTS: Six studies were included in the meta-analysis.
      The pooled sensitivity of AFI and WLB was 0.89 (95% confidence interval [CI] 0.81
      0.94) and 0.67 (95% CI 0.46-0.83) and the pooled specificity of AFI and WLB was
      0.64 (95% CI 0.37-0.84) and 0.84 (95% CI 0.74-0.91), respectively. The diagnostic
      odds ratio for AFI and WLB was 14.5 (95% CI 3.76-55.63) and 10.9 (95% CI 3.12
      38.21), and the area under the curve for AFI and WLB was 0.89 (95% CI 0.86-0.92)
      and 0.85 (95% CI 0.81-0.88), respectively. The pooled positive and negative
      likelihood ratios were 2.5 (95% CI 1.21-4.97) and 0.17 (95% CI 0.08-0.36) for
      AFI, and the corresponding values for WLB were 4.3 (95% CI 2.13-8.52) and 0.39
      (95% CI 0.21-0.73). The pooled positive likelihood ratio for AFI and WLB was not
      higher than 10, and the pooled negative likelihood ratio for AFI and WLB was not
      lower than 0.1. CONCLUSION: The sensitivity of AFI is higher than that of WLB,
      while the specificity of AFI is lower than that of WLB. The overall diagnostic
      performance of AFI is slightly better than that of WLB in detecting lung cancers
      and precancerous lesions. AFI should find its place in routine bronchoscopic
      examination and may improve the diagnostic outcome on endoscopy.

PMID- 23874086
TI  - Adequate prescribing of medication does not necessarily translate into good
      control of diabetes mellitus.
AB  - BACKGROUND: Patients with diabetes mellitus in Lithuania have access to almost
      all the latest blood glucose-lowering drugs available in the rest of the world.
      This study evaluated the effects of prescribing of treatment (oral medications,
      insulin, or both) in Lithuanian patients with type 1 or 2 diabetes and poor blood
      glucose control. METHODS: The relevant information was obtained from specialized
      questionnaires completed by 26 consulting endocrinologists in Lithuania between
      October 1, 2008 and December 31, 2008. The study cohort comprised 865 randomly
      selected patients with diabetes mellitus and a glycosylated (HbA1c) level >=7%.
      In total, there were 95 patients with type 1 diabetes and 770 with type 2
      diabetes. RESULTS: Linear regression for patients with type 1 diabetes revealed a
      weak trend towards higher doses of insulin reflecting lower HbA1c values. The
      mean dose of insulin in patients with type 1 diabetes before an endocrinology
      consultation was 57.1 +/- 15.7 U/day (0.8 +/- 0.2 U/kg), which increased
      significantly to 63.3 +/- 16.5 U/day (0.9 +/- 0.2 U/kg) after an endocrinology
      consultation (P < 0.05). Treatment prescribed for patients with type 2 diabetes
      depended on the duration of disease. Earlier treatment recommended for 68% of
      patients with type 2 diabetes was subsequently changed by the endocrinologist.
      Linear regression showed that the insulin dose prescribed before a specialist
      consultation as well as that recommended by an endocrinologist was significantly
      correlated with body mass index. CONCLUSION: Appropriate prescribing of blood
      glucose-lowering drugs does not always translate into good metabolic control of
      diabetes mellitus. The mean HbA1c was 8.5% +/- 1.3% in patients with type 2
      diabetes treated with oral drugs alone versus 9.0% +/- 1.3% in those treated with
      insulin alone.

PMID- 23874087
TI  - Two-year clinical outcomes after coronary drug-eluting stent placement in Chinese
      men and women: a multicenter, prospective registry study.
AB  - BACKGROUND: Previous studies have reported a discrepancy in baseline
      characteristics and outcomes after percutaneous coronary intervention between men
      and women. However, this finding has never been verified in the Chinese
      population. The present study analyzed two-year clinical outcomes after placement
      of coronary drug-eluting stents in Chinese men and women. METHODS: From January
      2005 to December 2010, a total of 3804 Chinese patients (2776 men, 1028 women)
      who underwent drug-eluting stent implantation were studied prospectively. The
      primary endpoint was the composite major adverse cardiac event (MACE) rate,
      including myocardial infarction, cardiac death, and target vessel
      revascularization at two years. Stent thrombosis served as the safety endpoint.
      Propensity score matching was used to compare the adjusted MACE rate between the
      two groups. RESULTS: At two-year follow-up, unadjusted rates of myocardial
      infarction, non-ST segment elevation myocardial infarction, target vessel
      revascularization, and MACE were significantly different between men (6.84%,
      4.6%, 13.1%, and 21.7%, respectively) and women (3.8% [P = 0.001], 2.0% [P <
      0.001] 10.3% [P = 0.025], and 16.3% [P < 0.001], respectively). After propensity
      score matching, there were no significant differences in composite MACE and
      individual endpoints at two years between the genders. CONCLUSION: Despite all
      the unfavorable risk factor clustering in women and complex coronary disease in
      men, the two-year clinical outcomes after coronary stent placement were
      comparable between Chinese women and men.

PMID- 23874088
TI  - Definitions, variants, and causes of nonadherence with medication: a challenge
      for tailored interventions.
AB  - BACKGROUND: Nonadherence with medication is a complex and multidimensional health
      care problem. The causes may be related to the patient, treatment, and/or health
      care provider. As a consequence, substantial numbers of patients do not benefit
      optimally from pharmacotherapy, resulting in increased morbidity and mortality as
      well as increased societal costs. Several interventions may contribute to
      improved adherence. However, most interventions have only a modest effect. Thus,
      despite the many efforts made, there has been little progress made as yet in
      tackling the problem of nonadherence. METHODS: This paper summarizes the
      definitions and taxonomy of adherence with medication, as well as types and
      causes of nonadherence. In addition, interventions aimed at improvement of
      adherence are discussed. CONCLUSION: There is not just one solution for the
      nonadherence problem that fits all patients. Most interventions to improve
      adherence are aimed at all patients regardless of whether they are adherent or
      not. Recently, a number of tailored interventions have been described in the
      literature. Modern techniques are useful. Electronic pill boxes combined with
      Short Message Service reminders are specifically designed to improve
      unintentional adherence and have resulted in an increase in refill adherence in
      diabetic patients with suboptimal adherence. Tailored Internet interventions are
      a possibility for influencing patient drug-taking behavior and show promising
      results. Tailored counseling interventions targeted at the underlying causes of
      nonadherence seem an attractive method for supporting patients with their use of
      drugs. However, despite the plausible theoretical framework, data on long-term
      health effects of the various interventions are not available. To improve
      adherence effectively, there is a need for a tailored approach based on the type
      and cause of nonadherence and the specific needs of the patient.

PMID- 23874089
TI  - Critical appraisal of the efficacy, safety, and patient acceptability of
      hydroxyprogesterone caproate injection to reduce the risk of preterm birth.
AB  - Prevention of preterm delivery is a major desiderate in contemporary obstetrics
      and a societal necessity. The means to achieve this goal remain elusive.
      Progesterone has been used in an attempt to prevent preterm delivery since the
      1970s, but the evidence initially accumulated was fraught by mixed results and
      was based on mostly underpowered studies with variable eligibility criteria,
      including history of spontaneous abortion as an indication for treatment. More
      recent randomized controlled clinical trials restimulated the interest in
      progesterone supplementation, suggesting that progesterone may favorably
      influence the rate of preterm delivery. Preterm delivery is a complex disorder
      and consequently it is unlikely that one generalized prevention strategy will be
      effective in all patients. Further, an additional impediment in accepting
      progesterone as the "magic bullet" in the prevention of preterm delivery is that
      its mechanism of action is not fully understood and the optimal formulations,
      route of administration, and dose have yet to be established. We have concerned
      ourselves in this review with the most recent status of 17 alpha
      hydroxyprogesterone caproate (17OH-PC) supplementation for prevention of preterm
      delivery. Our intention is to emphasize the efficacy, safety, and patient
      acceptability of this intervention, based on a comprehensive and unbiased review
      of the available literature. Currently there are insufficient data to suggest
      that 17OH-PC is superior or inferior to natural progesterone. Based on available
      evidence, we suggest a differential approach giving preferential consideration to
      either 17OH-PC or other progestins based on obstetric history and cervical
      surveillance. Progestin therapy for risk factors other than a history of preterm
      birth and/or a short cervix in the current pregnancy is not currently supported
      by the published evidence. The experience to date with 17OH-PC indicates that
      there are population subgroups that may be harmed by administration of 17OH-PC.
      Therefore, extending the use of 17OH-PC to unstudied populations or for
      indications that are not evidence-based is inadvisable outside of a research
      protocol. 

PMID- 23874090
TI  - Association of treatment and outcomes of doctor-shopping behavior in patients
      with hepatocellular carcinoma.
AB  - BACKGROUND: A variety of unfulfilled needs may trigger doctor-shopping behavior
      (DSB) in patients. In oncology, treatment results usually cause patients the most
      concern. This study investigated the association of DSB with active treatments
      received by patients with hepatocellular carcinoma (HCC) and outcomes. METHODS:
      With approval from the institutional review board, all patients registered in the
      cancer database of a teaching hospital and diagnosed as having HCC by self
      referral from outside hospitals or by in-house diagnosis were retrospectively
      identified. Patient data were then reviewed and analyzed via electronic medical
      records. RESULTS: Hepatitis B carriers were significantly more likely than
      noncarriers to show first-time DSB. Recurrent disease was less likely to result
      in DSB than predicted. Patients from outside hospitals not receiving upfront
      first treatment after diagnosis were significantly more likely to show more
      frequent DSB than those receiving it. Male patients eligible for salvage
      treatment were less likely to have frequent occurrences of DSB than their female
      counterparts. Receiving first salvage treatment was not associated with more
      frequent DSB. Treatment recommendations offered in the study hospital did not
      influence patients' decisions to leave or stay. Only elderly patients (>70 years)
      were less likely to show DSB. CONCLUSION: DSB can occur throughout the entire
      course of treatment for HCC for a variety of reasons. Active treatments, disease
      status, and patient characteristics all exerted an influence on DSB.

PMID- 23874091
TI  - Associations between cognitive abilities and life satisfaction in the oldest-old.
      Results from the longitudinal population study Good Aging in Skane.
AB  - INTRODUCTION: Studies on the associations between cognitive abilities and life
      satisfaction (LS) in the oldest-old are few. The aim of this study was to explore
      whether abilities in six different cognitive domains could predict LS in the
      oldest-old 3 years later. METHODS: The study population consisted of 681
      individuals aged 78-98 years, drawn from the longitudinal population study "Good
      Aging in Skane," which is part of a national survey (The Swedish National Study
      on Aging and Care). Scores on 13 cognitive tests were related to scores on
      Neugartens' LS index A (LSI-A) 3 years later. The cognitive tests were added into
      six different cognitive domains. A multiple regression analysis was constructed
      for each cognitive domain separately, with scores on the LSI-A as the dependent
      variable. The model was adjusted stepwise for sex, age, education, functional
      capacity, and depressive mood. RESULTS: Significant correlations were found
      between digit cancellation, word recall, verbal fluency (VF) A, VF animals, VF
      occupations, and mental rotations at baseline, as well as LSI-A at follow-up. The
      domains of spatial abilities (B = 0.453, P = 0.014) and processing speed (B =
      0.118, P = 0.020) remained significantly associated with LSI-A 3 years later
      after adjustment. CONCLUSION: The cognitive domains of spatial abilities and
      processing speed predicted LS 3 years later in the oldest-old. Clinical
      implications are discussed.

PMID- 23874092
TI  - Relative risk of pulmonary embolism in the very elderly compared with the
      elderly.
AB  - BACKGROUND: Pulmonary embolism (PE) can be an acute, life-threatening emergency,
      and studies suggest that advanced age is a risk factor for this condition.
      However, the literature is scarce regarding PE in patients above the age of 90
      years. This study examined the relative risk for PE in the very elderly (>90
      years) compared with that in the elderly (80-89 years). METHODS: A retrospective
      study was performed examining very elderly patients diagnosed with PE in the
      Department of Internal Medicine at the University Hospital Homburg/Saar in
      Germany between 2004 and 2012. Elderly patients (aged 80-89 years) diagnosed with
      PE served as controls. PE was confirmed by contrast-enhanced chest computed
      tomography or ventilation perfusion scintigraphy in both groups. A total of 2230
      patients were examined for PE in this study. Of these, 15 (0.67%) in the study
      group and 197 (8.83%) in the control group underwent further evaluation for PE.
      RESULTS: After performing a radiological examination, 11 (73.3%, including six
      [54.55%] women) of the 15 study patients (mean age 91.6 +/- 1.67 years) and 148
      (75.1%, including 93 [62.84%] women) of the 197 controls (mean age 84.0 +/- 2.59
      years) were confirmed to have PE. There was a significantly lower proportion of
      the very elderly enrolled in the study (P < 0.001). There were no significant
      differences in clinical presentation, cardiovascular risk factors,
      electrocardiograms, blood gas analyses, radiological diagnoses, or acute
      comorbidities between the groups. However, the very elderly were more likely to
      experience minor bleeding in the extremities (P = 0.016) and to have more chronic
      diseases (P < 0.001). An increased relative risk of PE was not detected in the
      very elderly (relative risk 0.98, P = 0.88). Furthermore, D-dimer, troponin T,
      and high-sensitive troponin T levels had limited predictive value for PE in the
      very elderly. There were no significant differences in the number of hospital
      admissions, intensive care or ward treatments, or duration of hospitalization.
      CONCLUSION: The relative risk for PE in the very elderly is not higher than that
      in the elderly.

PMID- 23874093
TI  - The development and pilot testing of the self-management programme of activity,
      coping and education for chronic obstructive pulmonary disease (SPACE for COPD).
AB  - PURPOSE: There is no independent standardized self-management approach available
      for chronic obstructive pulmonary disease (COPD). The aim of this project was to
      develop and test a novel self-management manual for individuals with COPD.
      PATIENTS: Participants with a confirmed diagnosis of COPD were recruited from
      primary care. METHODS: A novel self-management manual was developed with health
      care professionals and patients. Five focus groups were conducted with
      individuals with COPD (N = 24) during development to confirm and enhance the
      content of the prototype manual. The Self-management Programme of Activity,
      Coping and Education for Chronic Obstructive Pulmonary Disease (SPACE for COPD)
      manual was developed as the focus of a comprehensive self-management approach
      facilitated by health care professionals. Preference for delivery was initial
      face-to-face consultation with telephone follow-up. The SPACE for COPD manual was
      piloted with 37 participants in primary care. Outcome measures included the Self
      Report Chronic Respiratory Questionnaire, Incremental Shuttle Walk Test, and
      Endurance Shuttle Walking Test (ESWT); measurements were taken at baseline and 6
      weeks. RESULTS: The pilot study observed statistically significant improvements
      for the dyspnea domain of the Self-Report Chronic Respiratory Questionnaire and
      ESWT. Dyspnea showed a mean change of 0.67 (95% confidence interval 0.23-1.11, P
      = 0.005). ESWT score increased by 302.25 seconds (95% confidence interval 161.47
      443.03, P < 0.001). CONCLUSION: This article describes the development and
      delivery of a novel self-management approach for COPD. The program, incorporating
      the SPACE for COPD manual, appears to provoke important changes in exercise
      capacity and breathlessness for individuals with COPD managed in primary care.

PMID- 23874094
TI  - Efficacy of levofloxacin versus cefuroxime in treating acute exacerbations of
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Antibiotic treatment is one of the major pharmacologic treatments for
      acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However,
      the choice of antibiotic depends on the local resistance pattern. A multicenter,
      randomized, controlled trial was done in patients with AECOPD to compare the
      efficacy of levofloxacin with that of cefuroxime axetil. METHODS: Patients with
      AECOPD and without radiographic evidence of pneumonia were enrolled and
      randomized to either levofloxacin 500 mg daily or cefuroxime 250 mg twice daily
      in the mildmoderate exacerbation group, or 500 mg twice daily in the severe
      exacerbation group, for seven days. Clinical efficacy and microbiologic response
      were evaluated 5-7 days after the last dose. RESULTS: Treatment was clinically
      successful in 90.4% of patients in the levofloxacin group, and in 90.6% of
      patients in the cefuroxime group (95% confidence interval -9.40 to 10.91), within
      a noninferiority margin of 10%. The microbiologic response appeared to be higher
      in the levofloxacin group, but the difference was not statistically significant.
      The safety profile was similar in both groups. CONCLUSION: Levofloxacin is not
      inferior to cefuroxime with regard to clinical efficacy in treating AECOPD.

PMID- 23874095
TI  - Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and
      folate receptor-mediated endocytosis by molecular targeted nanomedicine.
AB  - Immunohistochemistry and an immunofluorescence technique was used to detect
      folate receptor expression in tissue samples and cell lines of head and neck
      squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16
      tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5
      8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic
      resonance imaging were used to observe endocytosis of folate-conjugated cisplatin
      loaded magnetic nanoparticles (CDDP-FA-ASA-MNP) in cultured cells and
      transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36) of the head
      and neck squamous carcinomas expressed the folate receptor versus none in the
      control group (0/24). Only the HNE-1 and Hep-2 cell lines expressed the folate
      receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP
      was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A
      similar result was seen in transplanted tumors in nude mice. Magnetic resonance
      imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors
      on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in
      CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell
      strongly expressed the folate receptor, while normal tissue did not. The folate
      receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines,
      and lays the foundation for molecular targeted treatment of cancer. 

PMID- 23874096
TI  - Computational study on the interactions and orientation of monoclonal human
      immunoglobulin G on a polystyrene surface.
AB  - Having a theoretical understanding of the orientation of immunoglobulin on an
      immobilized solid surface is important in biomedical pathogen-detecting systems
      and cellular analysis. Despite the stable adsorption of immunoglobulin on a
      polystyrene (PS) surface that has been applied in many kinds of immunoassays,
      there are many uncertainties in antibody-based clinical and biological
      experimental methods. To understand the binding mechanism and physicochemical
      interactions between immunoglobulin and the PS surface at the atomic level, we
      investigated the binding behavior and interactions of the monoclonal
      immunoglobulin G (IgG) on the PS surface using the computational method. In our
      docking simulation with the different arrangement of translational and rotational
      orientation of IgG onto the PS surface, three typical orientation patterns of the
      immunoglobulin G on the PS surface were found. We precisely analyzed these
      orientation patterns and clarified how the immunoglobulin G interacts with the PS
      surface at atomic scale in the beginning of the adsorption process. Major driving
      forces for the adsorption of IgG onto the PS surface come from serine (Ser),
      aspartic acid (Asp), and glutamic acid (Glu) residues. 

PMID- 23874097
TI  - The efficacy of Li in bipolar disorder.

PMID- 23874098
TI  - Reduced dorsolateral prefrontal cortical hemodynamic response in adult obsessive
      compulsive disorder as measured by near-infrared spectroscopy during the verbal
      fluency task.
AB  - BACKGROUND: Near-infrared spectroscopy has helped our understanding of the
      neurobiological mechanisms of psychiatric disorders and has advantages including
      noninvasiveness, lower cost, and ease of use compared with other imaging
      techniques, like functional magnetic resonance imaging. The verbal fluency task
      is the most common and well established task used to assess cognitive activation
      during near-infrared spectroscopy. Recent functional neuroimaging studies have
      shown that the orbitofrontal cortex and other brain regions, including the
      dorsolateral prefrontal cortex, may play important roles in the pathophysiology
      of obsessive-compulsive disorder (OCD). This study aimed to evaluate hemodynamic
      responses in the dorsolateral prefrontal cortex in patients with OCD using near
      infrared spectroscopy during the verbal fluency task and to compare these with
      dorsolateral prefrontal cortex responses in healthy controls. METHODS: Twenty
      patients with OCD and 20 controls matched for age, gender, handedness, and
      estimated intelligence quotient participated in this study. The verbal fluency
      task was used to elicit near-infrared spectroscopic activation and consisted of a
      30-second pre-task, followed by three repetitions of a 20-second verbal fluency
      task (total 60 seconds), followed by a 70-second post-task period. The near
      infrared spectroscopy experiment was conducted on the same day as surveys of
      obsessive-compulsive symptoms, depression, and anxiety. Z-scores for changes in
      the concentration of oxygenated hemoglobin were compared between the OCD patients
      and controls in 14 channels set over the left and right dorsolateral prefrontal
      cortex and frontopolar areas. RESULTS: During the verbal fluency task,
      significant task-related activation was detected in both the OCD group and the
      controls. Changes in oxygenated hemoglobin concentration in the right
      dorsolateral prefrontal cortex were significantly smaller in the OCD group than
      in the controls, but were not statistically significant after correction for
      multiple comparisons. CONCLUSION: Patients with OCD have reduced prefrontal,
      especially right dorsolateral prefrontal, cortical hemodynamic responses as
      measured by near-infrared spectroscopy during the verbal fluency task. These
      results support the hypothesis that the dorsolateral prefrontal cortex plays a
      role in the pathophysiology of OCD.

PMID- 23874099
TI  - New drug classes for the treatment of partial onset epilepsy: focus on
      perampanel.
AB  - Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl]
      benzonitrile hydrate) is the latest in the line of new antiepileptic drugs with a
      novel mechanism of action. Perampanel inhibits alpha-amino-3-hydroxy-5-methyl-4
      isoxazole-propionic acid (AMPA)-induced increases in intracellular Ca(2+) and
      selectively blocks AMPA receptor-mediated synaptic transmission, thus reducing
      neuronal excitation. Three Phase III multicenter, randomized, double-blind,
      placebo-controlled trials demonstrated the efficacy and good tolerability of
      perampanel as adjunctive treatment in patients with refractory partial-onset
      seizures. The drug is approved for use in the European Union and United States,
      with expected release onto the American market in June-September 2013, pending US
      Drug Enforcement Agency classification. The pharmacology of perampanel offers
      potential as more than just another new antiepileptic drug. This first-in-class
      drug will provide another option for practitioners of rational polytherapy. As an
      AMPA-receptor antagonist, perampanel may possess antiepileptogenic properties in
      addition to its demonstrated antiseizure properties. 

PMID- 23874100
TI  - The clinical efficacy of dabigatran etexilate for preventing stroke in atrial
      fibrillation patients.
AB  - The use of novel oral anticoagulants (NOACs) for stroke and systemic embolism
      prevention in the setting of specifically non valvular atrial fibrillation has
      provided clinicians with a realistic treatment alternative to the traditional
      dose-adjusted, warfarin-based anticoagulation that is targeted to a therapeutic
      international normalized ratio range of 2.0-3.0. We discuss the use of dabigatran
      in the setting of mechanical heart valves, atrial fibrillation or left atrial
      catheter ablation procedures, reversal of the drug in the setting of adverse
      bleeding events, and background on the molecular biology and development of this
      novel treatment for stroke reduction. 

PMID- 23874102
TI  - Impact of hypoglycemia on daily life of type 2 diabetes patients in Ukraine.
AB  - This study evaluates the impact of hypoglycemia on the lives of Ukrainian
      patients with type 2 diabetes mellitus. The secondary objective was to explore
      patient-physician relationships and the attitudes of patients towards various
      informational resources on diabetes management. Three focus groups with 26
      patients were conducted. Qualitative information was evaluated using content
      analysis. The results show that patients with type 2 diabetes mellitus in Ukraine
      are adapting to potential attacks of hypoglycemia; however, they still experience
      periodic manifestations of hypoglycemia that significantly affect their
      psychological well-being. This result is similar to observations made in other
      countries. Ukrainian patients >40 years old mainly receive information on disease
      management from endocrinologists, and rarely use internet resources on diabetes
      management. Information provision was especially important at the early stage of
      the disease, when patients lack information on hypoglycemia manifestations and
      could therefore fail to identify and manage it properly. 

PMID- 23874101
TI  - Review and recommendations on management of refractory raised intracranial
      pressure in aneurysmal subarachnoid hemorrhage.
AB  - Intracranial hypertension is commonly encountered in poor-grade aneurysmal
      subarachnoid hemorrhage patients. Refractory raised intracranial pressure is
      associated with poor prognosis. The management of raised intracranial pressure is
      commonly referenced to experiences in traumatic brain injury. However,
      pathophysiologically, aneurysmal subarachnoid hemorrhage is different from
      traumatic brain injury. Currently, there is a paucity of consensus on the
      management of refractory raised intracranial pressure in spontaneous subarachnoid
      hemorrhage. We discuss in this paper the role of hyperosmolar agents,
      hypothermia, barbiturates, and decompressive craniectomy in managing raised
      intracranial pressure refractory to first-line treatment, in which preliminary
      data supported the use of hypertonic saline and secondary decompressive
      craniectomy. Future clinical trials should be carried out to delineate better
      their roles in management of raised intracranial pressure in aneurysmal
      subarachnoid hemorrhage patients. 

PMID- 23874103
TI  - Antioxidant vitamin levels among preschool children with uncomplicated Plasmodium
      falciparum malaria in Sokoto, Nigeria.
AB  - OBJECTIVE: To assess antioxidant vitamin levels among preschool children with
      plasmodium malarial infection. METHODS: We assessed antioxidant vitamin levels by
      using a standard procedure in 130 malaria-parasitized preschool children. Packed
      cell volume and parasite density were also evaluated. Forty healthy age- and
      gender-matched nonparasitized children were included as controls. RESULTS:
      Plasmodium falciparum was the causative species in all subjects. The mean malaria
      parasitemia was 4529.45 +/- 1237.5/MUL. The mean antioxidant concentrations for
      vitamins A, C, and E among plasmodium-parasitized subjects were 33.15 +/- 1.79
      MUg/dL, 0.51 +/- 0.02 mg/dL, and 0.61 +/- 0.02 mg/dL, respectively. The mean
      concentrations of vitamins A, C, and E among the non-malaria-parasitized controls
      were 69.72 +/- 1.71 MUg/dL, 1.25 +/- 0.04 mg/dL, and 1.31 +/- 0.04 mg/dL
      respectively. We observed that the mean antioxidant concentrations of vitamins A,
      C, and E were significantly lower among plasmodium-parasitized subjects compared
      with non-parasitized controls (P = 0.01). Malaria parasitemia correlated
      negatively with antioxidant concentrations and packed cell volume (r = -0.736 and
      -0.723, P = 0.001). We observed that the higher the level of parasitemia, the
      lower the antioxidant concentration. CONCLUSION: Our study has shown that the
      antioxidant levels in plasmodium-parasitized children in the North-West of
      Nigeria are low and that the more severe the malarial infection, the lower the
      antioxidant level and the packed cell volume. One key strategic intervention is
      the provision of early diagnosis and prompt effective treatment. We recommend
      that malaria-parasitized children, particularly those in the North-West of
      Nigeria, be placed routinely on antioxidant vitamins to manage the micronutrient
      deficiencies seen in these children. There is also the need for the promotion of
      insecticide-treated bed nets, intermittent preventive treatment, and effective
      case management of malarial illness among children.

PMID- 23874105
TI  - MicroRNA-145 downregulation associates with advanced tumor progression and poor
      prognosis in patients suffering osteosarcoma.
AB  - PURPOSE: Microribonucleic acid (miRNA)-145 (miR-145) has been identified as a
      tumor suppressor in several types of human cancers. Especially, miR-145
      expression has been found to be significantly decreased in osteosarcoma tissues,
      and enforced expression of this miRNA could inhibit invasion and angiopoiesis of
      osteosarcoma cells. However, its clinical significance in osteosarcoma is still
      unclear. Therefore, the aim of this study was to analyze the association of miR
      145 expression with clinicopathologic features and prognosis in patients
      suffering osteosarcoma. METHODS: miR-145 expression was detected by quantitative
      real-time reverse transcriptase polymerase chain reaction analysis using 166
      pairs of osteosarcoma and noncancerous bone tissues. Then, the associations of
      miR-145 expression with clinicopathological factors or survival of patients
      suffering osteosarcoma were determined. RESULTS: The expression levels of miR-145
      in osteosarcoma tissues were significantly lower than those in corresponding
      noncancerous bone tissues (P < 0.0001). In addition, miR-145 downregulation more
      frequently occurred in osteosarcoma specimens with advanced clinical stage (P =
      0.003) and positive distant metastasis (P = 0.008). Moreover, the univariate
      analysis demonstrated that osteosarcoma patients with low miR-145 expression had
      poorer overall (P = 0.003) and disease-free survival (P < 0.001). Furthermore,
      the multivariate analysis identified low miR-145 expression as an independent
      prognostic factor for both overall (P = 0.01) and disease-free survival (P =
      0.008). CONCLUSION: For the first time, the current data offer convincing
      evidence that the down-regulation of miR-145 may be associated with tumor
      aggressiveness and tumor metastasis of osteosarcoma, and that this miRNA may be
      an independent prognostic marker for osteosarcoma patients.

PMID- 23874104
TI  - Circulating nucleic acids in plasma and serum (CNAPS): applications in oncology.
AB  - The presence of small amounts of circulating nucleic acids in plasma and serum
      (CNAPS) is not a new finding. The verification that such amounts are
      significantly increased in cancer patients, and that CNAPS might carry a variety
      of genetic and epigenetic alterations related to cancer development and
      progression, has aroused great interest in the scientific community in the last
      decades. Such alterations potentially reflect changes that occur during
      carcinogenesis, and include DNA mutations, loss of heterozygosity, viral genomic
      integration, disruption of microRNA, hypermethylation of tumor suppressor genes,
      and changes in the mitochondrial DNA. These findings have led to many efforts
      toward the implementation of new clinical biomarkers based on CNAPS analysis. In
      the present article, we review the main findings related to the utility of CNAPS
      analysis for early diagnosis, prognosis, and monitoring of cancer, most of which
      appear promising. However, due to the lack of harmonization of laboratory
      techniques, the heterogeneity of disease progression, and the small number of
      recruited patients in most of those studies, there has been a poor translation of
      basic research into clinical practice. In addition, many aspects remain unknown,
      such as the release mechanisms of cell-free nucleic acids, their biological
      function, and the way by which they circulate in the bloodstream. It is therefore
      expected that in the coming years, an improved understanding of the relationship
      between CNAPS and the molecular biology of cancer will lead to better diagnosis,
      management, and treatment. 

PMID- 23874107
TI  - Evaluation of host quality of life and immune function in breast cancer patients
      treated with combination of adjuvant chemotherapy and oral administration of
      Lentinula edodes mycelia extract.
AB  - PURPOSE: Anthracycline-based chemotherapies for breast cancer are well known to
      have adverse effects and can also negatively affect host immune function. There
      is therefore a necessity for an adjuvant that maintains the quality of life (QOL)
      and immune function of cancer patients receiving anthracycline-based
      chemotherapies. PATIENTS AND METHODS: The present study investigated the
      effectiveness of the concomitant use of Lentinula edodes mycelia extract (LEM),
      an oral immunomodulator, with FEC75 (5-fluorouracil + epirubicin +
      cyclophosphamide) therapy on host QOL and immune function in breast cancer
      patients with nodal metastases. Ten breast cancer patients with nodal metastases
      receiving surgery were enrolled in this study. Treatment with 5-fluorouracil (500
      mg/m(2)), epirubicin (75 mg/m(2)), and cyclophosphamide (500 mg/m(2)) was
      performed every 21 days for two courses, and LEM (1800 mg/day by mouth) was
      administered during the second course. RESULTS: In the first course,
      hematological toxicity was observed and host QOL and immune function were
      exacerbated. In the second course, however, the number of white blood cells and
      lymphocytes did not decrease and host QOL was maintained. Furthermore, the
      cytotoxic activities of natural killer (NK) and lymphokine-activated killer cells
      and the proportion of activated NK and NK T-cells in lymphocytes were maintained
      in the second course. CONCLUSION: It has been suggested that the concomitant use
      of LEM with FEC75 therapy can maintain host QOL and immune function, and offer
      important implications for an application of LEM as a useful oral adjuvant to
      anthracycline-based chemotherapies.

PMID- 23874106
TI  - Glycoprotein non-metastatic b (GPNMB): A metastatic mediator and emerging
      therapeutic target in cancer.
AB  - Molecularly targeted therapies are rapidly growing with respect to their clinical
      development and impact on cancer treatment due to their highly selective anti
      tumor action. However, many aggressive cancers such as triple-negative breast
      cancer (TNBC) currently lack well-defined therapeutic targets against which such
      agents can be developed. The identification of tumor-associated antigens and the
      generation of antibody drug-conjugates represent an emerging area of intense
      interest and growth in the field of cancer therapeutics. Glycoprotein non
      metastatic b (GPNMB) has recently been identified as a gene that is over
      expressed in numerous cancers, including TNBC, and often correlates with the
      metastatic phenotype. In breast cancer, GPNMB expression in the tumor epithelium
      is associated with a reduction in disease-free and overall survival. Based on
      these findings, glembatumumab vedotin (CDX-011), an antibody-drug conjugate that
      selectively targets GPNMB, is currently being investigated in clinical trials for
      patients with metastatic breast cancer and unresectable melanoma. This review
      discusses the physiological and potential pathological roles of GPNMB in normal
      and cancer tissues, respectively, and details the clinical advances and
      challenges in targeting GPNMB-expressing malignancies. 

PMID- 23874108
TI  - Combined use of cyclophosphamide and Chalone 19-peptide in experimental breast
      cancer.
AB  - BACKGROUND: Cyclophosphamide is a potent anticancer drug, but its clinical
      utility is limited because of its severe side effects, in particular liver
      damage. Chalone 19-peptide induces apoptosis of tumor cells and inhibits tumor
      growth. The present study investigated the antitumor effects of a combination of
      cyclophosphamide and Chalone 19-peptide in experimental breast cancer. METHODS:
      An animal model of breast cancer was developed, consisting of an MDA-MB-231 cell
      line implanted in the nude mouse. Eight doses of a combination of
      cyclophosphamide 50 mg/kg or 100 mg/kg and Chalone 19-peptide 6.6 mg/kg were
      administered, and the mice were euthanized 28 days after the final drug
      injection. Histopathologic analysis of tumor size, metastasis, and apoptosis of
      cancer cells was performed. Control mice were injected intraperitoneally with
      either cyclophosphamide alone or the same volume of solvent. RESULTS: Tumor sizes
      in the treatment groups were smaller than in the controls. No metastasis was
      found in the groups treated with cyclophosphamide and Chalone 19-peptide, but
      lung metastasis was found in controls. Liver damage in the groups treated with
      cyclophosphamide was more serious than in the other groups. CONCLUSION: Addition
      of Chalone 19-peptide can improve the ability of cyclophosphamide to inhibit
      tumor growth and also reduces side effects.

PMID- 23874109
TI  - Clinical significance of B7-H4 expression in matched non-small cell lung cancer
      brain metastases and primary tumors.
AB  - BACKGROUND: B7-H4, a member of the inhibitory B7 family, is shown to have a
      profound inhibitory effect on the proliferation, activation, cytokine secretion,
      and development of cytotoxicity of T cells and may be involved in immune evasion
      in cancer patients. Although B7-H4 expression has been detected in non-small cell
      lung cancer (NSCLC), there are no published reports on the expression of B7-H4 in
      brain metastases from NSCLC. METHODS: We examined the expression of B7-H4 by
      immunohistochemistry in 49 cases of brain metastatic NSCLC, 18 cases of matched
      primary NSCLC, and 20 cases of NSCLC patients who had neither brain metastases
      nor other distant metastases. RESULTS: B7-H4 was highly expressed in 20 (40.8%)
      out of 49 brain metastases and two (11.1%) out of 18 matched primary tumors. The
      expression of B7-H4 in brain metastases appeared to be significantly higher than
      their matched primary tumors (P = 0.016). We also found that patients with high
      B7-H4 expression in their primary NSCLC have a higher risk of developing brain
      metastases (P = 0.022). Univariate analyses showed that median overall survival
      was significantly shorter in patients with high B7-H4 expression in brain
      metastases (P = 0.002). Multivariate analyses showed that B7-H4 was a significant
      independent prognostic indicator (P = 0.003). CONCLUSION: NSCLC patients with
      high B7-H4 expression may benefit from aggressive treatment and close
      surveillance. Furthermore, our study suggests that B7-H4 may play an important
      role in the metastatic process of NSCLC and is promising to be a new immune
      checkpoint molecule for future antitumoral immunotherapy.

PMID- 23874110
TI  - A miR-SNP of the XPO5 gene is associated with advanced non-small-cell lung
      cancer.
AB  - OBJECTIVES: MicroRNA (miRNA)-related single-nucleotide polymorphisms (SNPs) in
      miRNA processing machinery genes can affect cancer risk, treatment efficacy, and
      patient prognosis. A miR-SNP of rs11077 located in the 3' untranslated region (3'
      UTR) of the miRNA processing machinery gene XPO5 was examined in 112 advanced non
      small-cell lung cancer (NSCLC) patients to evaluate its association with cancer
      outcome. MATERIALS AND METHODS: The miR-SNP was genotyped with ligase detection
      reaction method. Survival curves were calculated using the Kaplan-Meier method,
      and multivariate survival analysis was performed using a Cox proportional hazards
      model. RESULTS: The AC genotype of rs11077, which carries C or A allele, was
      significantly associated with a better chemotherapy response (P = 0.001). In
      addition, rs11077 was independently associated with overall survival in advanced
      NSCLC patients through multivariate analysis (relative risk 0.457; 95% confidence
      interval: 0.251-0.831; P = 0.010). CONCLUSION: rs11077 was associated with
      chemotherapy response and survival of advanced NSCLC patients. The analysis of
      miR-SNPs in miRNA processing machinery genes can help identify patient subgroups
      that are at high risk for poor disease outcomes.

PMID- 23874111
TI  - Asymptomatic bacteriuria among elderly and middle-aged rural community-dwellers
      in South-Western Nigeria.
AB  - Asymptomatic bacteriuria in elderly individuals has been well described in
      institutionalized settings, but to a lesser extent in the community. The purpose
      of this study was to determine the pathogens responsible for asymptomatic
      bacteriuria in elderly and middle-aged individuals in Alajue-Ede, South-Western
      Nigeria, and to identify any associated factors. Mid-stream urine samples were
      collected from apparently healthy elderly and middle-aged volunteers who were
      participating in community health screening. Samples were processed and bacterial
      isolates were identified following standard procedures. In total, 128 volunteers
      (48 men, 76 women) participated in the study. Twenty-eight (22.6%) urinary
      pathogens were isolated, comprising Klebsiella species in five (17.9%),
      Pseudomonas aeruginosa in one (3.6%), Escherichia coli in 19 (67.9%), and Proteus
      species in three (10.7%) cases. Women were identified as being at higher risk of
      asymptomatic bacteriuria, and the prevalence also increased with increasing age
      in men. The elderly in this community have a high prevalence of asymptomatic
      bacteriuria, and screening for comorbid medical conditions may be of benefit. 

PMID- 23874112
TI  - Retrospective claims analysis of best supportive care costs and survival in a US
      metastatic renal cell population.
AB  - INTRODUCTION: Survival and best supportive care (BSC) costs for patients with
      metastatic renal cell carcinoma (mRCC), after stopping therapy, are poorly
      characterized yet an important aspect of patient care. This study examined
      survival and costs associated with BSC after one or two lines of therapy (LOTs)
      for mRCC. METHODS: A retrospective cohort analysis used claims data from
      commercially insured or Medicare Advantage Prescription Drug (MAPD) plan
      enrollees of a large United States health plan with an index RCC diagnosis (ICD-9
      CM 189.0) between January 1, 2007 and June 30, 2010; initiating any of the
      following therapies 30 days pre-index date through disenrollment from plan:
      sunitinib, temsirolimus, sorafenib, bevacizumab, everolimus, pazopanib,
      cytokines. LOT was identified using prescription fill and administration dates.
      Health care costs represent health plan- plus patient-paid amounts. RESULTS: The
      cohort (n = 274) was 73% male, with a mean age of 63.3 years (SD 11.1), with 80%
      commercially insured (20% MAPD), and 68% starting BSC following one LOT. Mean BSC
      duration was longer following one than two LOTs (223 [SD 260], 176 [SD 163]
      days). Median survival from the start of BSC was similar following one and two
      LOTs (126 and 118 days). Total BSC costs following one and two LOTs averaged
      US$50,188 (SD $96,984) and $37,295 (SD $51,102). Monthly costs for BSC following
      one and two LOTs ($10,151 and $10,566) were not substantially lower than costs
      while on treatment ($14,621 and $16,957). Inpatient hospital costs represented
      47% and 49% following one and two LOTs, with ambulatory costs of approximately
      36% following each LOT. CONCLUSION: Our study found similar survival and monthly
      costs for BSC following either one or two LOTs, with almost half of the cost
      reflecting inpatient care. Compared to costs on treatment ($14,621 to $16,957),
      BSC costs can be considerable ($10,151 to $10,566).

PMID- 23874113
TI  - Resource use and costs of exenatide bid or insulin in clinical practice: the
      European CHOICE study.
AB  - PURPOSE: CHOICE (CHanges to treatment and Outcomes in patients with type 2
      diabetes initiating InjeCtablE therapy) assessed patterns of exenatide bid and
      initial insulin therapy usage in clinical practice in six European countries and
      evaluated outcomes during the study. METHODS: CHOICE was a 24-month, prospective,
      noninterventional observational study. Clinical and resource use data were
      collected at initiation of first injectable therapy (exenatide bid or insulin)
      and at regular intervals for 24 months. Costs were evaluated from the national
      health care system perspective at 2009 prices. RESULTS: A total of 2515 patients
      were recruited. At the 24-month analysis, significant treatment change had
      occurred during the study in 42.2% of 1114 eligible patients in the exenatide bid
      cohort and 36.0% of 1274 eligible patients in the insulin cohort. Improvements in
      glycemic control were observed over the course of the study in both cohorts (P <
      0.001 for both), but mean weight was reduced in the exenatide bid cohort (P <
      0.001) and increased in the insulin cohort (P < 0.001) by 24 months. Across all
      countries, total per patient health care costs for the 24 months post baseline
      were ?3997.9 in the exenatide bid cohort and ?3265.5 in the insulin cohort
      (?1791.9 versus ?2465.5 due to costs other than those of injectable therapy).
      When baseline direct cost and patients' and disease characteristics were
      controlled for, mean direct costs differed by country (P < 0.0001), irrespective
      of treatment initiated, and the mean cost difference between treatments varied by
      country (P < 0.0001). CONCLUSION: Much of the higher mean cost of exenatide bid,
      compared with insulin, therapy was compensated for by lower mean costs of other
      health service utilization. Costs associated with exenatide bid or insulin
      initiation varied across countries, highlighting the need to avoid generalization
      of resource use and cost implications of a particular therapy when estimated in
      specific country settings.

PMID- 23874114
TI  - Association of FTO and PPARG polymorphisms with obesity in Portuguese women.
AB  - PURPOSE: We evaluated the association between risk of obesity in the Portuguese
      population and two obesity-related single-nucleotide gene polymorphisms: fat-mass
      and obesity-associated (FTO) rs9939609 and peroxisome proliferator-activated
      receptor gamma (PPARG) rs1801282. PATIENTS AND METHODS: A total of 194 Portuguese
      premenopausal female Caucasians aged between 18 and 50 years (95 with body mass
      index [BMI] >=30 g/m(2), 99 controls with BMI 18.5-24.9 kg/m(2)) participated in
      this study. The association of the single-nucleotide polymorphisms with obesity
      was determined by odds ratio calculation with 95% confidence intervals. RESULTS:
      Significant differences in allelic expression of FTO rs9939609 (P<0.05) were
      found between control and case groups, indicating a 2.5-higher risk for obesity
      in the presence of both risk alleles when comparing the control group with the
      entire obese group. A fourfold-higher risk was found for subjects with class III
      obesity compared to those with classes I and II. No significant differences in
      BMI were found between the control and case groups for PPARG rs1801282 (P>0.05).
      CONCLUSION: For the first time, a study involving an adult Portuguese population
      shows that individuals harboring both risk alleles in the FTO gene locus are at
      higher risk for obesity, which is in agreement to what has been reported for
      other European populations.

PMID- 23874115
TI  - Erosive pustular dermatosis (chronic atrophic dermatosis of the scalp and
      extremities).
AB  - Erosive pustular dermatosis is a rare noninfectious disease of the scalp or legs.
      Clinical findings are nonspecific, with crusts, atrophy, and pustules. A later
      complication of erosive pustular dermatosis is secondary cicatrical alopecia. The
      list of possible differential diagnoses is long, and includes infectious,
      inflammatory, and neoplastic dermatoses. Treatment is challenging. Topical drug
      therapy may improve the condition, but rarely results in a complete resolution.
      Surgery has been linked to exacerbation in some patients. In our hands, it
      achieved complete remission in male patients. 

PMID- 23874116
TI  - Glucose-6-phosphate dehydrogenase deficiency among children attending the
      Emergency Paediatric Unit of Usmanu Danfodiyo University Teaching Hospital,
      Sokoto, Nigeria.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common
      human enzyme deficiencies in the world. It is particularly common in populations
      living in malaria-endemic areas, affecting more than 400 million people
      worldwide. This present study was conducted with the aim of determining the
      prevalence of G6PD deficiency among children visiting the Emergency Paediatric
      Unit of Usmanu Danfodiyo University Teaching Hospital for pediatric-related care.
      The study included 118 children, made up of 77 (65.3%) males and 41 (34.7%)
      females aged <=5 years with mean age of 3.26 +/- 1.90 years. Randox G6PD
      quantitative in vitro test screening was used for the diagnosis of G6PD
      deficiency. Of the 118 children tested, 17 (14.4%) were G6PD-deficient.
      Prevalence of G6PD deficiency was concentrated predominantly among male children
      (22.1%). Male sex was significantly correlated with G6PD deficiency among the
      children studied (r = 7.85, P = 0.01). The highest prevalence occurred among
      children in the 2- to 5-year age-group. Of the 17 G6PD-deficient children, twelve
      (70.2%) were moderately deficient, while five (29.4%) were severely deficient.
      Blood film from G6PD-deficient children indicated the following morphological
      changes; Heinz bodies, schistocytes, target cells, nucleated red cells,
      spherocytes, and polychromasia. This present study has shown a high prevalence of
      G6PD deficiency among children residing in Sokoto in the northwestern
      geopolitical zone of Nigeria. The study indicated a male sex bias in the
      prevalence of G6PD deficiency among the children studied. There is a need for the
      routine screening of children for G6PD deficiency in our environment, to allow
      for evidence-based management of these children and to ensure the avoidance of
      food, drugs, and infective agents that can potentially predispose these children
      to oxidative stress as well as diseases that deplete micronutrients that protect
      against oxidative stress. There is need to build capacity in our setting among
      pediatricians to ensure the effective management of children with G6PD
      deficiency. 

PMID- 23874117
TI  - Knowledge, attitude, and practices of infertility among Saudi couples.
AB  - INTRODUCTION: Infertility places a huge psychological burden on infertile
      couples, especially for women. Greater knowledge of the factors affecting
      fertility may help to decrease the incidence of infertility by allowing couples
      to avoid certain risk factors. The aim of our study was (1) to assess the
      knowledge and attitudes of infertile and fertile Saudi participants on
      infertility, possible risk factors, and social consequences; and (2) to determine
      the practices of infertile Saudi couples to promote their fertility before having
      them attend an in vitro fertilization (IVF) clinic. METHODS AND MATERIALS: We
      conducted a cross-sectional study on 277 fertile participants from outpatient
      clinics and 104 infertile patients from the IVF clinic at King Abdulaziz Medical
      City between June 24, 2012 and July 4, 2012, using a previously validated
      interview questionnaire. Descriptive and analytical statistics were applied with
      a significance threshold of P <= 0.05. RESULTS: A generally poor level of
      knowledge (59%) and a neutral attitude (76%) toward infertility were reported by
      participants. Mistaken beliefs commonly held by the study participants regarding
      the causes of infertility were Djinns and supernatural causes (58.8%), black
      magic (67.5%), intrauterine devices (71.3%), and contraceptive pills (42.9%). The
      healer/Sheikh was reported as the primary and secondary preference for
      infertility treatment by 6.7% and 44.2% of IVF patients, respectively. Compared
      with fertile patients, IVF patients were significantly less likely to favor
      divorce (38.5% versus 57.6%; P = 0.001) or marriage to a second wife (62.5%
      versus 86.2%; P < 0.001), if the woman could not have a baby. The patients with
      infertility had more favorable attitudes toward fertility drugs (87.5% versus
      68.4%; P = 0.003) and having a test tube baby (92.4% versus 70.3%; P < 0.001).
      Child adoption was accepted as an option for treatment by the majority of IVF
      patients (60.6%) and fertile outpatients (71.5%). Alternative treatments
      previously practiced by the IVF patients to improve fertility include practicing
      Ruqia (61%), using alternative medicine (42%), engaging in physical exercise
      (39%), eating certain foods (22%), and quitting smoking (12%). CONCLUSION: These
      findings have implications for health care providers regarding the reluctance
      that couples experiencing fertility problems may have, at least initially, to
      accept some interventions required for the couple to conceive.

PMID- 23874118
TI  - An autopsy case of pulmonary fissure induced by zygomycosis.
AB  - For immunodeficient patients, fungi are life-threatening pathogens. In this
      paper, we present an autopsy case of combined zygomycosis and aspergillosis. A
      female in her 70s on chronic hemodialysis was admitted to a hospital suffering
      bloody sputum, dyspnea, and fever, probably due to perinuclear anti-neutrophil
      cytoplasmic antibody-related vasculitis. Antibiotics were administered and
      immunosuppressive therapy was started, resulting in an improvement in her
      condition. Pneumonia later developed, followed by pulmonary bleeding and
      intractable pneumothorax from which she ultimately died. On autopsy, the upper
      lobe of the left lung was found to have hemorrhagic necrosis and showed a large
      longitudinal fissure. Microscopically, Zygomycota were observed in both the lungs
      and heart, while Aspergillus was found in the middle lobe of the right lung.
      Zygomycosis, which usually has a poor prognosis, is assumed to have induced
      hemorrhagic infarction of the lungs, inducing pulmonary bleeding and necrosis,
      despite the use of lipid formulations of amphotericin B, which are effective
      medicines against Zygomycota. 

PMID- 23874120
TI  - Anatomy of the Pain Centre waiting list at the Centre hospitalier de l'Universite
      de Montreal (CHUM).
AB  - BACKGROUND: Waiting list management at chronic pain clinics has become a serious
      problem throughout Canada. We analyzed the waiting list at the Centre hospitalier
      de l'Universite de Montreal (CHUM) Pain Centre. METHODS: The present study is an
      observational, prospective study. We used a specifically designed survey
      questionnaire. Survey findings were analyzed with descriptive statistical
      methods. RESULTS: A total of 270 patients were contacted; only 146 were included.
      Of these, 93 were women and 53 men. The average age was 55.9 years. Fifty-two
      percent of the patients were referred by a medical specialist; 34% by family
      physicians; 3% for emergency; and 11% unknown. The mean for pain score was
      6.7/10. Seventy-three percent were taking pain killers with an average
      improvement on their pain score of 52%. Ten percent of respondents were not
      taking any type of analgesic medication, while 17% were taking over-the-counter
      drugs. Fifty-three percent of the patients had been suffering from chronic pain
      for 5 years or less, while 10% had been suffering and awaiting specialized pain
      treatment for more than 20 years. CONCLUSION: Our data suggests that
      accessibility to specialized health care is not the sole obstacle to the timely
      and effective management of chronic pain. Seventy-three percent of the patients
      were taking some form of pharmaceutical treatment for pain and reported an
      average improvement rate of 52% on their pain score under medication. Such
      inconsistency may be attributable to patients' lack of compliance with their
      treatment. The World Health Organization Working Group recommended in chronic
      patients a novel approach to health care, based on patient therapeutic education.
      Our results show that patients need to acquire self-management skills regarding
      their chronic conditions.

PMID- 23874121
TI  - Systematic review and comparison of pharmacologic therapies for neuropathic pain
      associated with spinal cord injury.
AB  - BACKGROUND: Management of neuropathic pain (NeP) associated with spinal cord
      injury (SCI) is difficult. This report presents a systematic literature review
      and comparison of the efficacy and safety of pharmacologic therapies for treating
      SCI-associated NeP. METHODS: Medline, Embase, Cochrane, and Database of Abstracts
      of Reviews of Effects were searched through December 2011 for randomized,
      blinded, and controlled clinical trials of SCI-associated NeP meeting predefined
      inclusion criteria. Efficacy outcomes of interest were pain reduction on the 11
      point numeric rating scale (NRS) or 100 mm visual analog scale and proportion of
      patients achieving >=30% or >=50% pain reduction. Discontinuations and adverse
      events (AEs) were also assessed, for which Bayesian meta-analytic indirect
      comparisons were performed. RESULTS: Of the nine studies included in the
      analysis, samples were <100 patients, except for one pregabalin study (n = 136).
      Standard errors for the NRS outcome were often not reported, precluding
      quantitative comparisons across treatments. Estimated 11-point NRS pain reduction
      relative to placebo was -1.72 for pregabalin, -1.65 for amitriptyline, -1.0 for
      duloxetine, -1 (median) for levetiracetam, -0.27 for gabapentin, 1 (median) for
      lamotrigine, and 2 for dronabinol. Risk ratios relative to placebo for 30%
      improvement were 0.71 for levetiracetam and 2.56 for pregabalin, and 0.94 and
      2.91, respectively, for 50% improvement. Meta-analytic comparisons showed
      significantly more AEs with pregabalin and tramadol compared with placebo, and no
      differences between placebo and any treatment for discontinuations. CONCLUSIONS:
      Studies of SCI-associated NeP were few, small, and reported insufficient data for
      quantitative comparisons of efficacy. However, available data suggested
      pregabalin was associated with more favorable efficacy for all outcome measures
      examined, and that the risks of AEs and discontinuations were found to be similar
      among the therapies.

PMID- 23874122
TI  - Endotoxin-Induced IL-6 Promoter Activation in Skeletal Muscle Requires an NF
      kappaB Site.
AB  - Previous studies in monocytes and other cell types have provided evidence of a
      role for the NF-kappaB pathway in IL-6 induction. The purpose of the present
      study was to examine the involvement of NF-kappaB in the induction of the IL-6
      promoter in skeletal muscle cells by endotoxin (LPS), TNFalpha or IL-1alpha.
      Transfection of C2C12 mouse myocytes with a luciferase reporter under the control
      of the IL-6 promoter indicated each immunomodulator enhanced IL-6 promoter
      activity. Mutation and inhibitor studies indicate this response was dependent on
      the IL-6 NF-kappaB binding site, but independent of NF-IL6, AP-1, CREB or C/EBP.
      Cotransfection with an expression vector which constitutively activates the RelA
      pathway increased IL-6 promoter activity, and activity could not be further
      enhanced by cytokines or LPS. However, cotransfecting various dominant negative
      upstream NF-kappaB kinase expression vectors which inhibited RelA or RelB
      pathways either individually or in combination had no effect on LPS-induced
      activation of the IL-6 promoter, but abolished induction from a NF-kappaB-based
      promoter. This lack of effect was not due to a lack of NF-kappaB pathway
      activation in C2C12 myocytes because both Western analysis and EMSA supershifting
      showed an LPS-induced increase in nuclear RelA and RelA phosphorylation. However,
      another protein was observed bound to the IL-6 NF-kappaB site that does not bind
      to a consensus NF-kappaB site. The present findings provide novel insights
      regarding inflammation-induced stimulation of IL-6 promoter activity in skeletal
      muscle which is an important but non-traditional component of the innate immune
      system.

PMID- 23874123
TI  - Mothers' human papilloma virus knowledge and willingness to vaccinate their
      adolescent daughters in Lagos, Nigeria.
AB  - INTRODUCTION: Human papillomavirus (HPV) is one of the most common sexually
      transmitted infections in sexually active adolescents and young women and has
      been implicated as a cause of the majority of cases of cervical cancer, which is
      the second most common cancer in women in Nigeria. HPV is preventable with the
      use of HPV vaccines. OBJECTIVES: The objective of this study was to assess
      mothers' HPV knowledge and their willingness to vaccinate their adolescent
      daughters in Lagos, Nigeria. MATERIALS AND METHODS: This study was a community
      based, descriptive cross-sectional study carried out in July, 2012 in Shomolu
      Local Government Area (LGA) of Lagos State, Nigeria. Multistage sampling method
      was employed to select the 290 respondents who participated in the study.
      Structured, pretested, interviewer-administered questionnaires were used for data
      collection. Data was analyzed with Epi InfoTM version 7. RESULTS: The study
      revealed low awareness of HPV (27.9%) and HPV vaccines (19.7%) among the mothers
      that participated. There was a high awareness for cervical cancer but little
      knowledge of its link to HPV. Awareness and utilization of HPV vaccines increased
      with increasing educational level (P < 0.05). There was a high willingness and
      intention among the mothers to vaccinate their girls (88.9%) and to recommend the
      vaccine to others (91.0%). Accessibility and affordability of the HPV vaccines
      were found to be possible barriers to future utilization of the vaccines.
      CONCLUSION: Despite low knowledge about HPV and HPV vaccines, mothers were
      willing to vaccinate their daughters. We recommend improving mothers' knowledge
      by education and the possible inclusion of the vaccine in the national
      immunization schedule to eliminate the financial barrier.

PMID- 23874119
TI  - Long-term opioid treatment of chronic nonmalignant pain: unproven efficacy and
      neglected safety?
AB  - BACKGROUND: For the past 30 years, opioids have been used to treat chronic
      nonmalignant pain. This study tests the following hypotheses: (1) there is no
      strong evidence-based foundation for the conclusion that long-term opioid
      treatment of chronic nonmalignant pain is effective; and (2) the main problem
      associated with the safety of such treatment - assessment of the risk of
      addiction - has been neglected. METHODS: Scientometric analysis of the articles
      representing clinical research in this area was performed to assess (1) the
      quality of presented evidence (type of study); and (2) the duration of the
      treatment phase. The sufficiency of representation of addiction was assessed by
      counting the number of articles that represent (1) editorials; (2) articles in
      the top specialty journals; and (3) articles with titles clearly indicating that
      the addiction-related safety is involved (topic-in-title articles). RESULTS: Not
      a single randomized controlled trial with opioid treatment lasting >3 months was
      found. All studies with a duration of opioid treatment >=6 months (n = 16) were
      conducted without a proper control group. Such studies cannot provide the
      consistent good-quality evidence necessary for a strong clinical recommendation.
      There were profound differences in the number of addiction articles related
      specifically to chronic nonmalignant pain patients and to opioid addiction in
      general. An inadequate number of chronic pain-related publications were observed
      with all three types of counted articles: editorials, articles in the top
      specialty journals, and topic-in-title articles. CONCLUSION: There is no strong
      evidence-based foundation for the conclusion that long-term opioid treatment of
      chronic nonmalignant pain is effective. The above identified signs indicating
      neglect of addiction associated with the opioid treatment of chronic nonmalignant
      pain were present.

PMID- 23874124
TI  - Perception on prevention of mother-to-child-transmission (PMTCT) of HIV among
      women of reproductive age group in Osogbo, Southwestern Nigeria.
AB  - INTRODUCTION: The fastest growing group of adults living with human
      immunodeficiency virus (HIV), is women. As more women contract the virus, the
      number of children infected in utero, intra-partum, and during breastfeeding has
      been growing. This study assessed the knowledge and attitude of women of child
      bearing age towards the prevention of mother-to-child-transmission (PMTCT) of
      HIV. MATERIALS AND METHODS: This is a descriptive cross sectional survey of 420
      women of the reproductive age group (15-49 years) selected using a multistage
      sampling technique. Data were obtained using interviewer-administered, pretested,
      semistructured questionnaires. The data were analyzed using the Statistical
      Package for Social Sciences (SPSS) software version 15. RESULTS: A high level of
      awareness about HIV/acquired immunodeficiency syndrome (AIDS) was observed among
      the respondents (99.8%). The knowledge about MTCT and PMTCT of HIV was high,
      92.1% and 91.4%, respectively. However, a significant portion (71.27%) of the
      study population had poor attitudes towards PMTCT of HIV. CONCLUSION: Despite the
      high level of awareness of HIV/AIDS, and good knowledge about MTCT and PMTCT of
      HIV/AIDS among the respondents, the attitude towards PMTCT is poor. There is need
      for the involvement of the stakeholders in bridging the gap between knowledge and
      attitude of prevention of MTCT of HIV among women.

PMID- 23874125
TI  - Blood transfusion trends in obstetrics at the Federal Teaching Hospital in
      Abakaliki, South-East Nigeria.
AB  - BACKGROUND: Obstetric hemorrhage has been repeatedly implicated as a leading
      cause of maternal mortality in Nigeria, yet there are very few studies that
      evaluate the practice of blood transfusion in obstetrics as a life saving
      measure. OBJECTIVES: The aim of this study was to evaluate the practice of
      obstetric blood transfusion, the mean decision-transfusion interval, and the
      outcome in parturients who had blood transfusions. METHODS: This was a
      prospective descriptive study conducted at the Federal Teaching Hospital,
      Abakaliki, South-East Nigeria, between 1st January, 2012 and 31st December, 2012.
      Statistical analysis was done using SPSS version 15.0 for Windows. RESULTS: Out
      of 151 parturients who received blood transfusion, 141/151 (97.4%) were
      knowledgeable about blood transfusion, while only 10/151 (2.6%) had no knowledge
      of it. The hospital was the source of information for 120/151 (80.8%) of the
      participants. Blood transfusion rate was 7.04% of all parturients. The mean
      decision-transfusion interval was 12.0 +/- 4.3 hours. All participants were
      transfused with either whole blood or sedimented cells. The mean number of blood
      units transfused was 1.77 +/- 0.93 units. The indications for transfusion were:
      anemia, 109/151 (72.2%); shock, 13/151 (8.6%); postpartum hemorrhage, 23/151
      (15.2%); antepartum hemorrhage, 6 (4%). Six (4%) women died; mortality was due to
      renal failure in 3/6 (50%) and disseminated intravascular coagulopathy in 3/6
      (50%). These deaths were due to delays and difficulty in securing blood for
      transfusion, while those who got transfused on time were salvaged with minimal
      morbidity, 21/151 (14%), or with no morbidity, 130/151 (86%). CONCLUSION:
      Excessive blood loss and anemia still complicate most pregnancies in our practice
      and the mean decision-transfusion interval is unacceptably long with debilitating
      maternal morbidity and mortality that can be improved with safe and effective
      blood transfusion with minimal or no risk.

PMID- 23874126
TI  - The protective effects of lafutidine for bortezomib induced peripheral
      neuropathy.
AB  - Peripheral neuropathy (PN) caused by bortezomib is an important complication of
      multiple myeloma. Subcutaneous injection of bortezomib reduced PN, but 24% of
      cases were grade 2 PN and 6% of cases were grade 3 PN. PN higher than grade 2 was
      not resolved by subcutaneous injection. PN higher than grade 3 has serious dose
      limiting toxicity and is the cause of discontinuing bortezomib treatment.
      Lafutidine is an H2-blocker with gastroprotective activity and is thought to
      function by increasing mucosal blood flow via capsaicin sensitive neurons. The
      same activity of lafutidine is considered to improve glossodynia and taxane
      induced PN. We hypothesized that lafutidine prevents or improves PN that is
      caused by bortezomib. In the current study, bortezomib was administered in the
      usual manner (intravenous administration of bortezomib 1.3 mg/m(2), twice a week
      for 2 weeks, followed by 1 week without treatment) for up to four cycles to
      compare our data with other studies. Lafutidine was administered orally at a dose
      of 10 mg twice daily. In our eight evaluated cases, the total occurrence of PN
      was four out of eight patients (50%). There were only grade 1 PN (4 out of 8)
      cases, and no cases higher than grade 2. We conclude that (1) the total
      occurrence of PN was not improved, (2) there was no PN after the first course,
      (3) there were only grade 1 cases and there were no cases higher than grade 2,
      and (4) no cases discontinued bortezomib treatment because of PN. This is the
      first report showing that lafutidine is useful for the amelioration of bortezomib
      induced PN. 

PMID- 23874128
TI  - New records and an annotated key for the identification of graphis adans. In
      South Korea.
AB  - The following new species for the lichen genus Graphis in Korea are reported: G.
      chlorotica, G. nanodes and G. tenuirima. A brief description of these species,
      together with their distribution, ecology, and illustrations are provided. A key
      to all known species of this genus from Korea is also presented. 

PMID- 23874127
TI  - Lipolytic enzymes involved in the virulence of human pathogenic fungi.
AB  - Pathogenic microbes secrete various enzymes with lipolytic activities to
      facilitate their survival within the host. Lipolytic enzymes include
      extracellular lipases and phospholipases, and several lines of evidence have
      suggested that these enzymes contribute to the virulence of pathogenic fungi.
      Candida albicans and Cryptococcus neoformans are the most commonly isolated human
      fungal pathogens, and several biochemical and molecular approaches have
      identified their extracellular lipolytic enzymes. The role of lipases and
      phospholipases in the virulence of C. albicans has been extensively studied, and
      these enzymes have been shown to contribute to C. albicans morphological
      transition, colonization, cytotoxicity, and penetration to the host. While not
      much is known about the lipases in C. neoformans, the roles of phospholipases in
      the dissemination of fungal cells in the host and in signaling pathways have been
      described. Lipolytic enzymes may also influence the survival of the lipophilic
      cutaneous pathogenic yeast Malassezia species within the host, and an unusually
      high number of lipase-coding genes may complement the lipid dependency of this
      fungus. This review briefly describes the current understanding of the lipolytic
      enzymes in major human fungal pathogens, namely C. albicans, C. neoformans, and
      Malassezia spp. 

PMID- 23874129
TI  - Ectomycorrhizal Fungal Communities of Red Pine (Pinus densiflora) Seedlings in
      Disturbed Sites and Undisturbed Old Forest Sites.
AB  - This study aimed to investigate differences in ectomycorrhizal (ECM) fungal
      communities between disturbed sites and undisturbed old forest sites. ECM root
      tips of Pinus densiflora were collected from 4 sites disturbed by human
      activities and 3 undisturbed old forest sites adjacent to the disturbed sites.
      Results in this study showed that the number of ECM root tips, species diversity,
      and number of species were significantly higher in the disturbed sites than in
      the undisturbed sites, suggesting that the ECM fungal community structure was
      affected by the degree of disturbance. 

PMID- 23874130
TI  - Diversity and seasonal variation of endophytic fungi isolated from three conifers
      in mt. Taehwa, Korea.
AB  - The needled leaves of three conifer species were collected in Mt. Taehwa during
      different seasons of the year. Total 59 isolates and 19 species of endophytic
      fungi were isolated from the leaves and identified using morphological and
      molecular characteristics. As a result, Shannon index was different in its host
      plant; Larix kaempferi had a highest value of species diversity. According to the
      sampling season, 9 species of 19 species were isolated during fall season. The
      results suggest that the existing of host plant and sampling season are major
      factors of distribution of endophytic fungi. 

PMID- 23874131
TI  - Development of SCAR Markers for the Identification of Phytophthora katsurae
      Causing Chestnut Ink Disease in Korea.
AB  - Sequence characterized amplified region (SCAR) markers are one of the most
      effective and accurate tools for microbial identification. In this study, we
      applied SCAR markers for the rapid and accurate detection of Phytophthora
      katsurae, the casual agent of chestnut ink disease in Korea. In this study, we
      developed seven SCAR markers specific to P. katsurae using random amplified
      polymorphic DNA (RAPD), and assessed the potential of the SCAR markers to serve
      as tools for identifying P. katsurae. Seven primer pairs (SOPC 1F/SOPC 1R, SOPC 1
      1F/SOPC 1-1R, SOPC 3F/SOPC 3R, SOPC 4F/SOPC 4R, SOPC 4F/SOPC 4-1R, SOPD 9F/SOPD
      9R, and SOPD 10F/SOPD 10R) from a sequence derived from RAPD fragments were
      designed for the analysis of the SCAR markers. To evaluate the specificity and
      sensitivity of the SCAR markers, the genomic DNA of P. katsurae was serially
      diluted 10-fold to final concentrations from 1 mg/mL to 1 pg/mL. The limit of
      detection using the SCAR markers ranged from 100 ug/mL to 100 ng/mL. To identify
      the limit for detecting P. katsurae zoospores, each suspension of zoospores was
      serially diluted 10-fold to final concentrations from 10 * 10(5) to 10 * 10(1)
      zoospores/mL, and then extracted. The limit of detection by SCAR markers was
      approximately 10 * 10(1) zoospores/mL. PCR detection with SCAR markers was
      specific for P. katsurae, and did not produce any P. katsurae-specific PCR
      amplicons from 16 other Phytophthora species used as controls. This study shows
      that SCAR markers are a useful tool for the rapid and effective detection of P.
      katsurae. 

PMID- 23874132
TI  - Hypolipidaemic Effect of Hericium erinaceum Grown in Artemisia capillaris on
      Obese Rats.
AB  - In this study, ethanolic extracts from Hericium erinaceum cultivated with
      Artemisia capillaris (HEAC) were assessed for their ability to lower the
      cholesterol levels of male Sprague-Dawley rats fed a high-fat diet. Rats were
      randomly subdivided into seven test groups. Each group contained eight rats fed a
      high-fat diet during a growth period lasting 4 wk. Supplementation with the
      extracts was performed once a day for 2 wk after the high-fat diet. The control
      group (rats fed a high-fat diet) showed a high efficiency ratio (feed efficiency
      ratio) value compared to the normal group. Biochemical parameters, including
      total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and
      triglyceride (TG) levels dramatically increased in the control group compared to
      the normal group. High-density lipoprotein-cholesterol (HDL-c) content in the
      control group was also significantly lower relative to the normal group. Two
      positive control groups, treated with simvastatin and atorvastatin, had lowered
      TC, LDL-c, and TG levels, and increased HDL-c content compared to the control
      group. Treatment with the tested extracts, including HEAC, ethanolic extracts
      from Hericium erinaceum, and ethanolic extracts from Artemisia capillaris reduced
      TC, LDL-c, and TG levels and elevated HDL-c content in the hyperlipidemia rats.
      The atherogenic index and cardiac risk factor values for the HEAC-treated group
      were 0.95 and 1.95, respectively. Simvastatin- and atorvastatin-treated groups
      showed atherogenic index values of 1.56 and 1.69, respectively, and cardiac risk
      factor values of 2.56 and 2.69, respectively. These results show HEAC possesses
      an ability to cure hyperlipidemia in rats and may serve as an effective natural
      medicine for treating hyperlipidemia in humans. 

PMID- 23874133
TI  - Mycoflora of soybeans used for meju fermentation.
AB  - Diverse fungi are present in Korean traditional meju and they are known to play
      an important role in fermented soybean products. To determine the origin of the
      fungi in meju, we examined the mycoflora of soybeans from 10 traditional meju
      factories. The samples were untreated or treated with sodium hypochlorite, and
      placed on malt extract agar (MEA), dichloran 18% glycerol agar (DG18), and
      dichloran rose bengal chloramphenicol agar (DRBC) medium. A total of 794 fungal
      strains were isolated and they were identified as 41 genera and 86 species. From
      sodium hypochlorite untreated soybeans, the genera, Cladosporium (55%), Eurotium
      (51%), Fusarium (33%), Penicillium (22%), and Aspergillus (exclusion of Eurotium)
      (20%), were mainly isolated, and Eurotium herbariorum (22%), Eurotium repens
      (18%), Cladosporium tenuissimum (18%), F. fujikuroi (18%), Aspergillus
      oryzae/flavus (7%), and Penicillium steckii (6%) were the predominant species. In
      case of sodium hypochlorite-treated soybeans, Eurotium (31%) and Cladosporium
      (5%) were frequently isolated, but Aspergillus (excluding Eurotium), Penicillium
      and Fusarium which were frequently isolated from untreated soybeans, were rarely
      isolated. Eurotium herbariorum (21%), Eurotium repens (8%), and Cladosporium
      tenuissimum (3%) were the predominant species. Of the 41 genera and 86 species
      isolated from soybeans, 13 genera and 33 species were also found in meju. These
      results suggest that the fungi on soybeans may influence the mycoflora of meju. 

PMID- 23874134
TI  - Bacillus sp. BS061 Suppresses Powdery Mildew and Gray Mold.
AB  - The use of a microorganism, or its secretions, to prevent plant disease offers an
      attractive alternative or supplement to synthetic fungicides for the management
      of plant disease without the negative effects of chemical control mechanisms.
      During a screening for microorganisms with the potential to be used as microbial
      fungicides, Bacillus sp. BS061 was isolated from a plant leaf. The strain BS061
      potently inhibited the mycelial growth of Botrytis cinerea, and significantly
      reduced disease incidence of powdery mildew in cucumber and strawberry. We also
      found that the culture filtrate of BS061 inhibited the mycelial growth of various
      plant pathogens. 

PMID- 23874135
TI  - A New Record of Penicillium cainii from Soil in Korea.
AB  - Twenty Penicillium isolates were recovered during the investigation of fungal
      community in the soil samples collected from Wando (Jeonnam Province, Korea).
      Among them, one species was identified and described as P. cainii based on
      phylogentic analysis of internal transcribed spacer and beta-tubulin (BT2) genes
      and morphological characteristics. This is a first report of P. cainii in Korea. 

PMID- 23874136
TI  - Three new records of penicillium species isolated from insect specimens in Korea.
AB  - Three Penicillium species have been isolated from insect specimens in Korea;
      Penicillium sp., P. steckii, and P. polonicum. Penicillium sp. (KNU12-3-2) was
      isolated from Lixus imperessiventris, while P. polonicum (KNU12-1-8) and
      Penicillium steckii (KNU12-2-9) were isolated from Muljarus japonicas and Meloe
      proscarabaeus, respectively. The identification was based on the morphological
      characteristics of the fungi and in internal transcribed spacer analysis. This is
      the first report on the isolation of these three species of Penicillium from
      insects in Korea. 

PMID- 23874137
TI  - Distribution of Particles in the Z-axis of Tissue Sections: Relevance for
      Counting Methods.
AB  - The distribution of particles in the z-axis of thick tissue sections has gained
      considerable attention, primarily because of implications for the accuracy of
      modern stereological counting methods. Three major types of artifacts can affect
      these sections: loss of particles from the surfaces of tissue sections (lost
      caps), homogeneous collapse in the z-axis, and differential deformation in the z
      axis. Initially it was assumed that thick sections were not compromised by
      differential shrinkage or compression (differential uniform deformation). Studies
      in the last decade showed that such artifacts are common and that they depend on
      embedding media and sectioning devices. Paraffin, glycolmethacrylate and
      vibratome sections are affected by this artifact, but not celloidin sections or
      cryostat-derived cryosections. Differential distribution of particles in the z
      axis is likely due to compression of the surface areas (margins) during
      sectioning, resulting in differential particle densities in the core and margin
      of tissue sections. This deformation of tissue sections can be rapidly assessed
      by measuring the position of particles in the z-axis. The analysis is complicated
      by potential secondary effects on section surfaces through loss of particles, the
      so-called "lost caps" phenomenon. Secondary effects necessitate the use of guard
      spaces, while their use in case of primary effects (compression due to
      sectioning) would enhance the artifact's impact on bias. Symmetric versus
      asymmetric patterns of z-axis distortion can give clues to distinguish primary
      and secondary effects. Studies that use the optical disector need to take these
      parameters into account to minimize biases.

PMID- 23874138
TI  - Current microbial isolates from wound swabs, their culture and sensitivity
      pattern at the niger delta university teaching hospital, okolobiri, Nigeria.
AB  - BACKGROUND: Wound infections continue to be problematic in clinical practice
      where empiric treatment of infections is routine. OBJECTIVES: A retrospective
      cross-sectional study to determine the current causative organisms of wound
      infections and their antibiotic susceptibility patterns in the Niger Delta
      University Teaching Hospital (NDUTH), Okolobiri, Bayelsa State of Nigeria.
      METHODS: Records of wound swabs collected from 101 patients with high suspicion
      of wound infection were analysed. Smears from the wound swabs were inoculated on
      appropriate media and cultured. Bacterial colonies were Gram stained and
      microscopically examined. Biochemical tests were done to identify pathogen
      species. The Kirby-Bauer disk diffusion method was used for antibiotic testing.
      RESULTS: Prevalence of wound infection was 86.13% (CI: 79.41-92.85). Most
      bacteria were Gram negative bacilli with Pseudomonas aeruginosa being the most
      prevalent pathogen isolated. The bacterial isolates exhibited a high degree of
      resistance to the antibiotics tested (42.8% to 100% resistance). All isolates
      were resistant to cloxacillin. Age group and sex did not exert any effect on
      prevalence, aetiological agent or antimicrobial resistance pattern. CONCLUSION:
      We suggest a multidisciplinary approach to wound management, routine
      microbiological surveillance of wounds, rational drug use and the institution of
      strong infection control policies.

PMID- 23874140
TI  - Vector control and surveillance operations in the republic of singapore.
AB  - Singapore is known for its comprehensive vector control methods that keep
      mosquito populations at low levels in the urban, tropical, and green city-state.
      This report describes the measures taken by the National Environment Agency on
      the basis of observations of vector control and surveillance activities in
      residential areas, construction sites, and foreign worker quarters. The
      government-led active operations dealt not only with mosquito control but also
      social issues in urban residential buildings where people with varying
      preferences live, the responsibilities of the business sector, and the education
      of multi-cultural/lingual residents and foreign workers. The public health
      measures implemented in Singapore offer useful ideas to countries/cities that
      have not yet established vector control programs against mosquito-borne
      infectious diseases. 

PMID- 23874141
TI  - Surge of dengue virus infection and chikungunya Fever in bali in 2010: the burden
      of mosquito-borne infectious diseases in a tourist destination.
AB  - Labor flow and travelers are important factors contributing to the spread of
      Dengue virus infection and chikungunya fever. Bali Province of Indonesia, a
      popular resort and tourist destination, has these factors and suffers from
      mosquito-borne infectious diseases. Using area study approach, a series of
      fieldwork was conducted in Bali to obtain up-to-date primary disease data, to
      learn more about public health measures, and to interview health officers, hotel
      personnel, and other resource persons. The national data including information on
      two other provinces were obtained for comparison. The health ministry reported
      5,810 and 11,697 cases of dengue hemorrhagic fever in Bali in 2009 and 2010,
      respectively. Moreover, two densely populated tourist areas and one district have
      shown a particularly high incidence and sharp increases in 2010. Cases of
      chikungunya fever reported in Bali more than doubled in 2010 from the previous
      year. Our findings suggest that Bali can benefit from a significant reduction in
      vector populations and dissemination of disease preventive knowledge among both
      local residents and foreign visitors. This will require a concerted and trans
      border approach, which may prove difficult in the province. 

PMID- 23874139
TI  - Development of Monoclonal Antibodies That Target 1-Cys Peroxiredoxin and
      Differentiate Plasmodium falciparum from P. vivax and P. knowlesi.
AB  - Prompt and accurate diagnosis of malarial patients is a crucial factor in
      controlling the morbidity and mortality of the disease. Effective treatment
      decisions require a correct diagnosis among mixed-species malarial patients.
      Differential diagnosis is particularly important in cases of Plasmodium vivax, a
      species that shares endemicity with P. falciparum in most endemic areas.
      Moreover, it is difficult to identify P. knowlesi on the basis of morphology
      alone, and rapid diagnostic tests are still not available for this malaria
      species. Therefore, the development of diagnostic tests applicable to the field
      is urgently needed. 1-Cys peroxiredoxin (1-Cys-Prx) in P. falciparum is
      abundantly expressed in the mature asexual stages, making it a promising
      candidate as a diagnostic antigen. In this study, we produced five monoclonal
      antibodies (mAbs) against P. falciparum 1-Cys-Prx (Pf1-Cys-Prx) by immunizing
      BALB/c mice with recombinant Pf1-Cys-Prx and subsequent hybridoma production.
      Cross reactivity of established mAbs with the orthologous molecule of Pf1-Cys-Prx
      in P. vivax (Pv1-Cys-Prx) and P. knowlesi (Pk1-Cys-Prx) was examined. Western
      blot analyses showed that three mAbs reacted with Pv1-Cys-Prx and Pk1-Cys-Prx but
      two mAbs did not. These results indicate that the two mAbs were effective in
      differentiating P. falciparum from P. vivax and P. knowlesi and could be used in
      differential diagnosis as well as comparative molecular studies of human
      Plasmodium species. 

PMID- 23874142
TI  - Empirical likelihood-based tests for stochastic ordering.
AB  - This paper develops an empirical likelihood approach to testing for the presence
      of stochastic ordering among univariate distributions based on independent random
      samples from each distribution. The proposed test statistic is formed by
      integrating a localized empirical likelihood statistic with respect to the
      empirical distribution of the pooled sample. The asymptotic null distribution of
      this test statistic is found to have a simple distribution-free representation in
      terms of standard Brownian bridge processes. The approach is used to compare the
      lengths of rule of Roman Emperors over various historical periods, including the
      "decline and fall" phase of the empire. In a simulation study, the power of the
      proposed test is found to improve substantially upon that of a competing test due
      to El Barmi and Mukerjee.

PMID- 23874144
TI  - Parameterized Complexity and Inapproximability of Dominating Set Problem in
      Chordal and Near Chordal Graphs.
AB  - In this paper, we study the parameterized complexity of Dominating Set problem in
      chordal graphs and near chordal graphs. We show the problem is W[2]-hard and
      cannot be solved in time no(k) in chordal and s-chordal (s > 3) graphs unless
      W[1]=FPT. In addition, we obtain inapproximability results for computing a
      minimum dominating set in chordal and near chordal graphs. Our results prove that
      unless NP=P, the minimum dominating set in a chordal or s-chordal (s > 3) graph
      cannot be approximated within a ratio of [Formula: see text] ln n in polynomial
      time, where n is the number of vertices in the graph and 0 < c < 1 is the
      constant from the inapproximability of the minimum dominating set in general
      graphs. In other words, our results suggest that restricting to chordal or s
      chordal graphs can improve the approximation ratio by no more than a factor of 3.
      We then extend our techniques to find similar results for the Independent
      Dominating Set problem and the Connected Dominating Set problem in chordal or
      near chordal graphs.

PMID- 23874145
TI  - Phosphate binding with a thiophene-based azamacrocycle in water.
AB  - Structural characterization of the phosphate complex with a thiophene-based
      macrocycle suggests that two dihydrogen phosphates in a dimeric form are
      encapsulated in the cavity via several hydrogen bonds from NH...O and CH...O
      interactions. In the lattice framework, the two dimers are linearly hydrogen
      bonded to form a tetramer. 1H NMR titrations suggest that the host forms a 1:1
      complex with phosphate, showing an association constant of 120 M-1 in D2O at pH =
      5.5. The host guest complexation was further confirmed by ESI-MS in a gas phase.

PMID- 23874143
TI  - Cultural Neuroscience.
AB  - Cultural neuroscience issues from the apparently incompatible combination of
      neuroscience and cultural psychology. A brief literature sampling suggests,
      instead, several preliminary topics that demonstrate proof of possibilities:
      cultural differences in both lower-level processes (e.g. perception, number
      representation) and higher-order processes (e.g. inferring others' emotions,
      contemplating the self) are beginning to shed new light on both culture and
      cognition. Candidates for future cultural neuroscience research include cultural
      variations in the default (resting) network, which may be social; regulation and
      inhibition of feelings, thoughts, and actions; prejudice and dehumanization; and
      neural signatures of fundamental warmth and competence judgments.

PMID- 23874146
TI  - Update in polycystic ovary syndrome: new criteria of diagnosis and treatment in
      Japan.
AB  - Polycystic ovary syndrome (PCOS) is the most frequent endocrine disorder in women
      of reproductive age. In 2006 the Japanese Society of Obstetrics and Gynecology
      (JSOG) proposed new, revised diagnostic criteria that in the future could also be
      valued internationally. Based on the new diagnostic criteria, the JSOG has also
      proposed the revised treatment criteria in 2008. In PCOS obese patients desiring
      children, weight loss and exercise is recommended. Nonobese patients, or those
      obese women who do not ovulate after lifestyle changes, are submitted to
      ovulation-induction therapy with clomiphene citrate (CC). Obese CC-resistant
      patients who have impaired glucose tolerance or insulin resistance are treated
      with a combination of metformin and CC. If these treatments options are
      unsuccessful, ovulation induction with exogenous gonadotropin therapy or
      laparoscopic ovarian drilling (LOD) is recommended. A low-dose step-up regimen is
      recommended with careful monitoring in order to reduce the risk of ovarian
      hyperstimulation syndrome (OHSS) and multiple pregnancies. Alternatively, with
      LOD high successful pregnancy rates of around 60 % are expected with a low risk
      of multiple pregnancies. If ovulation induction is unsuccessful, IVF-ET treatment
      is indicated. In high OHSS-risk patients, systematic embryo freezing and
      subsequent frozen embryo transfer cycles are recommended. In nonobese,
      anovulatory PCOS patients not desiring children, pharmacological treatments such
      as Holmstrom, Kaufmann regimens or low-dose oral anticonceptives are used to
      induce regular withdrawal bleeding. These treatments are especially important for
      preventing endometrial hyperplasia and endometrial cancer. These new diagnostic
      and treatment criteria hopefully will contribute to an improved care of PCOS
      patients in Japan.

PMID- 23874148
TI  - Diagnosing and Treating Co-morbid Sleep Apnea in Neurological Disorders, Part II.

PMID- 23874147
TI  - Affective Disorders, Bone Metabolism, and Osteoporosis.
AB  - The nature of the relationship between affective disorders, bone mineral density
      (BMD), and bone metabolism is unresolved, although there is growing evidence that
      many medications used to treat affective disorders are associated with low BMD or
      alterations in neuroendocrine systems that influence bone turnover. The objective
      of this review is to describe the current evidence regarding the association of
      unipolar and bipolar depression with BMD and indicators of bone metabolism, and
      to explore potential mediating and confounding influences of those relationships.
      The majority of studies of unipolar depression and BMD indicate that depressive
      symptoms are associated with low BMD. In contrast, evidence regarding the
      relationship between bipolar depression and BMD is inconsistent. There is limited
      but suggestive evidence to support an association between affective disorders and
      some markers of bone turnover. Many medications used to treat affective disorders
      have effects on physiologic systems that influence bone metabolism, and these
      conditions are also associated with a range of health behaviors that can
      influence osteoporosis risk. Future research should focus on disentangling the
      pathways linking psychotropic medications and their clinical indications with BMD
      and fracture risk.

PMID- 23874149
TI  - Distributive conjugal transfer in mycobacteria generates progeny with meiotic
      like genome-wide mosaicism, allowing mapping of a mating identity locus.
AB  - Horizontal gene transfer (HGT) in bacteria generates variation and drives
      evolution, and conjugation is considered a major contributor as it can mediate
      transfer of large segments of DNA between strains and species. We previously
      described a novel form of chromosomal conjugation in mycobacteria that does not
      conform to classic oriT-based conjugation models, and whose potential
      evolutionary significance has not been evaluated. Here, we determined the genome
      sequences of 22 F1-generation transconjugants, providing the first genome-wide
      view of conjugal HGT in bacteria at the nucleotide level. Remarkably,
      mycobacterial recipients acquired multiple, large, unlinked segments of donor
      DNA, far exceeding expectations for any bacterial HGT event. Consequently,
      conjugal DNA transfer created extensive genome-wide mosaicism within individual
      transconjugants, which generated large-scale sibling diversity approaching that
      seen in meiotic recombination. We exploited these attributes to perform genome
      wide mapping and introgression analyses to map a locus that determines conjugal
      mating identity in M. smegmatis. Distributive conjugal transfer offers a
      plausible mechanism for the predicted HGT events that created the genome
      mosaicism observed among extant Mycobacterium tuberculosis and Mycobacterium
      canettii species. Mycobacterial distributive conjugal transfer permits innovative
      genetic approaches to map phenotypic traits and confers the evolutionary benefits
      of sexual reproduction in an asexual organism. 

PMID- 23874150
TI  - Effects of resveratrol and SIRT1 on PGC-1alpha activity and mitochondrial
      biogenesis: a reevaluation.
AB  - It has been reported that feeding mice resveratrol activates AMPK and SIRT1 in
      skeletal muscle leading to deacetylation and activation of PGC-1alpha, increased
      mitochondrial biogenesis, and improved running endurance. This study was done to
      further evaluate the effects of resveratrol, SIRT1, and PGC-1alpha deacetylation
      on mitochondrial biogenesis in muscle. Feeding rats or mice a diet containing 4 g
      resveratrol/kg diet had no effect on mitochondrial protein levels in muscle. High
      concentrations of resveratrol lowered ATP concentration and activated AMPK in
      C2C12 myotubes, resulting in an increase in mitochondrial proteins. Knockdown of
      SIRT1, or suppression of SIRT1 activity with a dominant-negative (DN) SIRT1
      construct, increased PGC-1alpha acetylation, PGC-1alpha coactivator activity, and
      mitochondrial proteins in C2C12 cells. Expression of a DN SIRT1 in rat triceps
      muscle also induced an increase in mitochondrial proteins. Overexpression of
      SIRT1 decreased PGC-1alpha acetylation, PGC-1alpha coactivator activity, and
      mitochondrial proteins in C2C12 myotubes. Overexpression of SIRT1 also resulted
      in a decrease in mitochondrial proteins in rat triceps muscle. We conclude that,
      contrary to some previous reports, the mechanism by which SIRT1 regulates
      mitochondrial biogenesis is by inhibiting PGC-1alpha coactivator activity,
      resulting in a decrease in mitochondria. We also conclude that feeding rodents
      resveratrol has no effect on mitochondrial biogenesis in muscle.

PMID- 23874152
TI  - Quantitative assessment of the importance of phenotypic plasticity in adaptation
      to climate change in wild bird populations.
AB  - Predictions about the fate of species or populations under climate change
      scenarios typically neglect adaptive evolution and phenotypic plasticity, the two
      major mechanisms by which organisms can adapt to changing local conditions. As a
      consequence, we have little understanding of the scope for organisms to track
      changing environments by in situ adaptation. Here, we use a detailed individual
      specific long-term population study of great tits (Parus major) breeding in
      Wytham Woods, Oxford, UK to parameterise a mechanistic model and thus directly
      estimate the rate of environmental change to which in situ adaptation is
      possible. Using the effect of changes in early spring temperature on temporal
      synchrony between birds and a critical food resource, we focus in particular on
      the contribution of phenotypic plasticity to population persistence. Despite
      using conservative estimates for evolutionary and reproductive potential, our
      results suggest little risk of population extinction under projected local
      temperature change; however, this conclusion relies heavily on the extent to
      which phenotypic plasticity tracks the changing environment. Extrapolating the
      model to a broad range of life histories in birds suggests that the importance of
      phenotypic plasticity for adjustment to projected rates of temperature change
      increases with slower life histories, owing to lower evolutionary potential.
      Understanding the determinants and constraints on phenotypic plasticity in
      natural populations is thus crucial for characterising the risks that rapidly
      changing environments pose for the persistence of such populations. 

PMID- 23874151
TI  - Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron
      communication.
AB  - Reciprocal interactions between neurons and oligodendrocytes are not only crucial
      for myelination, but also for long-term survival of axons. Degeneration of axons
      occurs in several human myelin diseases, however the molecular mechanisms of axon
      glia communication maintaining axon integrity are poorly understood. Here, we
      describe the signal-mediated transfer of exosomes from oligodendrocytes to
      neurons. These endosome-derived vesicles are secreted by oligodendrocytes and
      carry specific protein and RNA cargo. We show that activity-dependent release of
      the neurotransmitter glutamate triggers oligodendroglial exosome secretion
      mediated by Ca2+ entry through oligodendroglial NMDA and AMPA receptors. In turn,
      neurons internalize the released exosomes by endocytosis. Injection of
      oligodendroglia-derived exosomes into the mouse brain results in functional
      retrieval of exosome cargo in neurons. Supply of cultured neurons with
      oligodendroglial exosomes improves neuronal viability under conditions of cell
      stress. These findings indicate that oligodendroglial exosomes participate in a
      novel mode of bidirectional neuron-glia communication contributing to neuronal
      integrity.

PMID- 23874153
TI  - Adapting to change.

PMID- 23874154
TI  - Key features of human episodic recollection in the cross-episode retrieval of rat
      hippocampus representations of space.
AB  - Neurophysiological studies focus on memory retrieval as a reproduction of what
      was experienced and have established that neural discharge is replayed to express
      memory. However, cognitive psychology has established that recollection is not a
      verbatim replay of stored information. Recollection is constructive, the product
      of memory retrieval cues, the information stored in memory, and the subject's
      state of mind. We discovered key features of constructive recollection embedded
      in the rat CA1 ensemble discharge during an active avoidance task. Rats learned
      two task variants, one with the arena stable, the other with it rotating; each
      variant defined a distinct behavioral episode. During the rotating episode, the
      ensemble discharge of CA1 principal neurons was dynamically organized to
      concurrently represent space in two distinct codes. The code for spatial
      reference frame switched rapidly between representing the rat's current location
      in either the stationary spatial frame of the room or the rotating frame of the
      arena. The code for task variant switched less frequently between a
      representation of the current rotating episode and the stable episode from the
      rat's past. The characteristics and interplay of these two hippocampal codes
      revealed three key properties of constructive recollection. (1) Although the
      ensemble representations of the stable and rotating episodes were distinct,
      ensemble discharge during rotation occasionally resembled the stable condition,
      demonstrating cross-episode retrieval of the representation of the remote, stable
      episode. (2) This cross-episode retrieval at the level of the code for task
      variant was more likely when the rotating arena was about to match its
      orientation in the stable episode. (3) The likelihood of cross-episode retrieval
      was influenced by preretrieval information that was signaled at the level of the
      code for spatial reference frame. Thus key features of episodic recollection
      manifest in rat hippocampal representations of space. 

PMID- 23874155
TI  - The shadow of bias.

PMID- 23874157
TI  - Production of alpha-galactosylceramide by a prominent member of the human gut
      microbiota.
AB  - While the human gut microbiota are suspected to produce diffusible small
      molecules that modulate host signaling pathways, few of these molecules have been
      identified. Species of Bacteroides and their relatives, which often comprise >50%
      of the gut community, are unusual among bacteria in that their membrane is rich
      in sphingolipids, a class of signaling molecules that play a key role in inducing
      apoptosis and modulating the host immune response. Although known for more than
      three decades, the full repertoire of Bacteroides sphingolipids has not been
      defined. Here, we use a combination of genetics and chemistry to identify the
      sphingolipids produced by Bacteroides fragilis NCTC 9343. We constructed a
      deletion mutant of BF2461, a putative serine palmitoyltransferase whose yeast
      homolog catalyzes the committed step in sphingolipid biosynthesis. We show that
      the Delta2461 mutant is sphingolipid deficient, enabling us to purify and solve
      the structures of three alkaline-stable lipids present in the wild-type strain
      but absent from the mutant. The first compound was the known sphingolipid
      ceramide phosphorylethanolamine, and the second was its corresponding
      dihydroceramide base. Unexpectedly, the third compound was the glycosphingolipid
      alpha-galactosylceramide (alpha-GalCer(Bf)), which is structurally related to a
      sponge-derived sphingolipid (alpha-GalCer, KRN7000) that is the prototypical
      agonist of CD1d-restricted natural killer T (iNKT) cells. We demonstrate that
      alpha-GalCer(Bf) has similar immunological properties to KRN7000: it binds to
      CD1d and activates both mouse and human iNKT cells both in vitro and in vivo.
      Thus, our study reveals BF2461 as the first known member of the Bacteroides
      sphingolipid pathway, and it indicates that the committed steps of the
      Bacteroides and eukaryotic sphingolipid pathways are identical. Moreover, our
      data suggest that some Bacteroides sphingolipids might influence host immune
      homeostasis.

PMID- 23874156
TI  - Evaluation of excess significance bias in animal studies of neurological
      diseases.
AB  - Animal studies generate valuable hypotheses that lead to the conduct of
      preventive or therapeutic clinical trials. We assessed whether there is evidence
      for excess statistical significance in results of animal studies on neurological
      disorders, suggesting biases. We used data from meta-analyses of interventions
      deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in
      Experimental Studies (CAMARADES). The number of observed studies with
      statistically significant results (O) was compared with the expected number (E),
      based on the statistical power of each study under different assumptions for the
      plausible effect size. We assessed 4,445 datasets synthesized in 160 meta
      analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis
      (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson
      disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found
      nominally (p<=0.05) statistically significant summary fixed effects. Assuming the
      effect size in the most precise study to be a plausible effect, 919 out of 4,445
      nominally significant results were expected versus 1,719 observed (p<10-9).
      Excess significance was present across all neurological disorders, in all
      subgroups defined by methodological characteristics, and also according to
      alternative plausible effects. Asymmetry tests also showed evidence of small
      study effects in 74 (46%) meta-analyses. Significantly effective interventions
      with more than 500 animals, and no hints of bias were seen in eight (5%) meta
      analyses. Overall, there are too many animal studies with statistically
      significant results in the literature of neurological disorders. This observation
      suggests strong biases, with selective analysis and outcome reporting biases
      being plausible explanations, and provides novel evidence on how these biases
      might influence the whole research domain of neurological animal literature.

PMID- 23874158
TI  - Dynactin subunit p150(Glued) is a neuron-specific anti-catastrophe factor.
AB  - Regulation of microtubule dynamics in neurons is critical, as defects in the
      microtubule-based transport of axonal organelles lead to neurodegenerative
      disease. The microtubule motor cytoplasmic dynein and its partner complex
      dynactin drive retrograde transport from the distal axon. We have recently shown
      that the p150(Glued) subunit of dynactin promotes the initiation of dynein-driven
      cargo motility from the microtubule plus-end. Because plus end-localized
      microtubule-associated proteins like p150(Glued) may also modulate the dynamics
      of microtubules, we hypothesized that p150(Glued) might promote cargo initiation
      by stabilizing the microtubule track. Here, we demonstrate in vitro using
      assembly assays and TIRF microscopy, and in primary neurons using live-cell
      imaging, that p150(Glued) is a potent anti-catastrophe factor for microtubules.
      p150(Glued) alters microtubule dynamics by binding both to microtubules and to
      tubulin dimers; both the N-terminal CAP-Gly and basic domains of p150(Glued) are
      required in tandem for this activity. p150(Glued) is alternatively spliced in
      vivo, with the full-length isoform including these two domains expressed
      primarily in neurons. Accordingly, we find that RNAi of p150(Glued) in
      nonpolarized cells does not alter microtubule dynamics, while depletion of
      p150(Glued) in neurons leads to a dramatic increase in microtubule catastrophe.
      Strikingly, a mutation in p150(Glued) causal for the lethal neurodegenerative
      disorder Perry syndrome abrogates this anti-catastrophe activity. Thus, we find
      that dynactin has multiple functions in neurons, both activating dynein-mediated
      retrograde axonal transport and enhancing microtubule stability through a novel
      anti-catastrophe mechanism regulated by tissue-specific isoform expression;
      disruption of either or both of these functions may contribute to
      neurodegenerative disease.

PMID- 23874159
TI  - A comparison of frameworks evaluating evidence for global health interventions.

PMID- 23874160
TI  - The effect of tobacco control measures during a period of rising cardiovascular
      disease risk in India: a mathematical model of myocardial infarction and stroke.
AB  - BACKGROUND: We simulated tobacco control and pharmacological strategies for
      preventing cardiovascular deaths in India, the country that is expected to
      experience more cardiovascular deaths than any other over the next decade.
      METHODS AND FINDINGS: A microsimulation model was developed to quantify the
      differential effects of various tobacco control measures and pharmacological
      therapies on myocardial infarction and stroke deaths stratified by age, gender,
      and urban/rural status for 2013 to 2022. The model incorporated population
      representative data from India on multiple risk factors that affect myocardial
      infarction and stroke mortality, including hypertension, hyperlipidemia,
      diabetes, coronary heart disease, and cerebrovascular disease. We also included
      data from India on cigarette smoking, bidi smoking, chewing tobacco, and
      secondhand smoke. According to the model's results, smoke-free legislation and
      tobacco taxation would likely be the most effective strategy among a menu of
      tobacco control strategies (including, as well, brief cessation advice by health
      care providers, mass media campaigns, and an advertising ban) for reducing
      myocardial infarction and stroke deaths over the next decade, while cessation
      advice would be expected to be the least effective strategy at the population
      level. In combination, these tobacco control interventions could avert 25% of
      myocardial infarctions and strokes (95% CI: 17%-34%) if the effects of the
      interventions are additive. These effects are substantially larger than would be
      achieved through aspirin, antihypertensive, and statin therapy under most
      scenarios, because of limited treatment access and adherence; nevertheless, the
      impacts of tobacco control policies and pharmacological interventions appear to
      be markedly synergistic, averting up to one-third of deaths from myocardial
      infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological
      therapies could also be considerably more potent with further health system
      improvements. CONCLUSIONS: Smoke-free laws and substantially increased tobacco
      taxation appear to be markedly potent population measures to avert future
      cardiovascular deaths in India. Despite the rise in co-morbid cardiovascular
      disease risk factors like hyperlipidemia and hypertension in low- and middle
      income countries, tobacco control is likely to remain a highly effective strategy
      to reduce cardiovascular deaths.

PMID- 23874161
TI  - Changes in association between previous therapeutic abortion and preterm birth in
      Scotland, 1980 to 2008: a historical cohort study.
AB  - BACKGROUND: Numerous studies have demonstrated that therapeutic termination of
      pregnancy (abortion) is associated with an increased risk of subsequent preterm
      birth. However, the literature is inconsistent, and methods of abortion have
      changed dramatically over the last 30 years. We hypothesized that the association
      between previous abortion and the risk of preterm first birth changed in Scotland
      between 1 January 1980 and 31 December 2008. METHODS AND FINDINGS: We studied
      linked Scottish national databases of births and perinatal deaths. We analysed
      the risk of preterm birth in relation to the number of previous abortions in
      732,719 first births (>=24 wk), adjusting for maternal characteristics. The risk
      (adjusted odds ratio [95% CI]) of preterm birth was modelled using logistic
      regression, and associations were expressed for a one-unit increase in the number
      of previous abortions. Previous abortion was associated with an increased risk of
      preterm birth (1.12 [1.09-1.16]). When analysed by year of delivery, the
      association was strongest in 1980-1983 (1.32 [1.21-1.43]), progressively declined
      between 1984 and 1999, and was no longer apparent in 2000-2003 (0.98 [0.91-1.05])
      or 2004-2008 (1.02 [0.95-1.09]). A statistical test for interaction between
      previous abortion and year was highly statistically significant (p<0.001).
      Analysis of data for abortions among nulliparous women in Scotland 1992-2008
      demonstrated that the proportion that were surgical without use of cervical pre
      treatment decreased from 31% to 0.4%, and that the proportion of medical
      abortions increased from 18% to 68%. CONCLUSIONS: Previous abortion was a risk
      factor for spontaneous preterm birth in Scotland in the 1980s and 1990s, but the
      association progressively weakened and disappeared altogether by 2000. These
      changes were paralleled by increasing use of medical abortion and cervical pre
      treatment prior to surgical abortion. Although it is plausible that the two
      trends were related, we could not test this directly as the data on the method of
      prior abortions were not linked to individuals in the cohort. However, we
      speculate that modernising abortion methods may be an effective long-term
      strategy to reduce global rates of preterm birth.

PMID- 23874162
TI  - Progress in using systematic reviews of animal studies to improve translational
      research.

PMID- 23874163
TI  - Sickle cell anaemia in a changing world.

PMID- 23874164
TI  - Global burden of sickle cell anaemia in children under five, 2010-2050: modelling
      based on demographics, excess mortality, and interventions.
AB  - BACKGROUND: The global burden of sickle cell anaemia (SCA) is set to rise as a
      consequence of improved survival in high-prevalence low- and middle-income
      countries and population migration to higher-income countries. The host of
      quantitative evidence documenting these changes has not been assembled at the
      global level. The purpose of this study is to estimate trends in the future
      number of newborns with SCA and the number of lives that could be saved in under
      five children with SCA by the implementation of different levels of health
      interventions. METHODS AND FINDINGS: First, we calculated projected numbers of
      newborns with SCA for each 5-y interval between 2010 and 2050 by combining
      estimates of national SCA frequencies with projected demographic data. We then
      accounted for under-five mortality (U5m) projections and tested different levels
      of excess mortality for children with SCA, reflecting the benefits of
      implementing specific health interventions for under-five patients in 2015, to
      assess the number of lives that could be saved with appropriate health care
      services. The estimated number of newborns with SCA globally will increase from
      305,800 (confidence interval [CI]: 238,400-398,800) in 2010 to 404,200 (CI:
      242,500-657,600) in 2050. It is likely that Nigeria (2010: 91,000 newborns with
      SCA [CI: 77,900-106,100]; 2050: 140,800 [CI: 95,500-200,600]) and the Democratic
      Republic of the Congo (2010: 39,700 [CI: 32,600-48,800]; 2050: 44,700 [CI: 27,100
      70,500]) will remain the countries most in need of policies for the prevention
      and management of SCA. We predict a decrease in the annual number of newborns
      with SCA in India (2010: 44,400 [CI: 33,700-59,100]; 2050: 33,900 [CI: 15,900
      64,700]). The implementation of basic health interventions (e.g., prenatal
      diagnosis, penicillin prophylaxis, and vaccination) for SCA in 2015, leading to
      significant reductions in excess mortality among under-five children with SCA,
      could, by 2050, prolong the lives of 5,302,900 [CI: 3,174,800-6,699,100] newborns
      with SCA. Similarly, large-scale universal screening could save the lives of up
      to 9,806,000 (CI: 6,745,800-14,232,700) newborns with SCA globally, 85% (CI: 81%
      88%) of whom will be born in sub-Saharan Africa. The study findings are limited
      by the uncertainty in the estimates and the assumptions around mortality
      reductions associated with interventions. CONCLUSIONS: Our quantitative approach
      confirms that the global burden of SCA is increasing, and highlights the need to
      develop specific national policies for appropriate public health planning,
      particularly in low- and middle-income countries. Further empirical collaborative
      epidemiological studies are vital to assess current and future health care needs,
      especially in Nigeria, the Democratic Republic of the Congo, and India.

PMID- 23874165
TI  - Consistent estimation of Gibbs energy using component contributions.
AB  - Standard Gibbs energies of reactions are increasingly being used in metabolic
      modeling for applying thermodynamic constraints on reaction rates, metabolite
      concentrations and kinetic parameters. The increasing scope and diversity of
      metabolic models has led scientists to look for genome-scale solutions that can
      estimate the standard Gibbs energy of all the reactions in metabolism. Group
      contribution methods greatly increase coverage, albeit at the price of decreased
      precision. We present here a way to combine the estimations of group contribution
      with the more accurate reactant contributions by decomposing each reaction into
      two parts and applying one of the methods on each of them. This method gives
      priority to the reactant contributions over group contributions while
      guaranteeing that all estimations will be consistent, i.e. will not violate the
      first law of thermodynamics. We show that there is a significant increase in the
      accuracy of our estimations compared to standard group contribution.
      Specifically, our cross-validation results show an 80% reduction in the median
      absolute residual for reactions that can be derived by reactant contributions
      only. We provide the full framework and source code for deriving estimates of
      standard reaction Gibbs energy, as well as confidence intervals, and believe this
      will facilitate the wide use of thermodynamic data for a better understanding of
      metabolism. 

PMID- 23874166
TI  - Optimal dynamics for quality control in spatially distributed mitochondrial
      networks.
AB  - Recent imaging studies of mitochondrial dynamics have implicated a cycle of
      fusion, fission, and autophagy in the quality control of mitochondrial function
      by selectively increasing the membrane potential of some mitochondria at the
      expense of the turnover of others. This complex, dynamical system creates
      spatially distributed networks that are dependent on active transport along
      cytoskeletal networks and on protein import leading to biogenesis. To study the
      relative impacts of local interactions between neighboring mitochondria and their
      reorganization via transport, we have developed a spatiotemporal mathematical
      model encompassing all of these processes in which we focus on the dynamics of a
      health parameter meant to mimic the functional state of mitochondria. In
      agreement with previous models, we show that both autophagy and the generation of
      membrane potential asymmetry following a fusion/fission cycle are required for
      maintaining a healthy mitochondrial population. This health maintenance is
      affected by mitochondrial density and motility primarily through changes in the
      frequency of fusion events. Health is optimized when the selectivity thresholds
      for fusion and fission are matched, providing a mechanistic basis for the
      observed coupling of the two processes through the protein OPA1. We also
      demonstrate that the discreteness of the components exchanged during fusion is
      critical for quality control, and that the effects of limiting total amounts of
      autophagy and biogenesis have distinct consequences on health and population
      size, respectively. Taken together, our results show that several general
      principles emerge from the complexity of the quality control cycle that can be
      used to focus and interpret future experimental studies, and our modeling
      framework provides a road-map for deconstructing the functional importance of
      local interactions in communities of cells as well as organelles. 

PMID- 23874167
TI  - A family of algorithms for computing consensus about node state from network
      data.
AB  - Biological and social networks are composed of heterogeneous nodes that
      contribute differentially to network structure and function. A number of
      algorithms have been developed to measure this variation. These algorithms have
      proven useful for applications that require assigning scores to individual nodes
      from ranking websites to determining critical species in ecosystems-yet the
      mechanistic basis for why they produce good rankings remains poorly understood.
      We show that a unifying property of these algorithms is that they quantify
      consensus in the network about a node's state or capacity to perform a function.
      The algorithms capture consensus by either taking into account the number of a
      target node's direct connections, and, when the edges are weighted, the
      uniformity of its weighted in-degree distribution (breadth), or by measuring net
      flow into a target node (depth). Using data from communication, social, and
      biological networks we find that that how an algorithm measures consensus-through
      breadth or depth- impacts its ability to correctly score nodes. We also observe
      variation in sensitivity to source biases in interaction/adjacency matrices:
      errors arising from systematic error at the node level or direct manipulation of
      network connectivity by nodes. Our results indicate that the breadth algorithms,
      which are derived from information theory, correctly score nodes (assessed using
      independent data) and are robust to errors. However, in cases where nodes "form
      opinions" about other nodes using indirect information, like reputation, depth
      algorithms, like Eigenvector Centrality, are required. One caveat is that
      Eigenvector Centrality is not robust to error unless the network is transitive or
      assortative. In these cases the network structure allows the depth algorithms to
      effectively capture breadth as well as depth. Finally, we discuss the algorithms'
      cognitive and computational demands. This is an important consideration in
      systems in which individuals use the collective opinions of others to make
      decisions. 

PMID- 23874168
TI  - The minimal complexity of adapting agents increases with fitness.
AB  - What is the relationship between the complexity and the fitness of evolved
      organisms, whether natural or artificial? It has been asserted, primarily based
      on empirical data, that the complexity of plants and animals increases as their
      fitness within a particular environment increases via evolution by natural
      selection. We simulate the evolution of the brains of simple organisms living in
      a planar maze that they have to traverse as rapidly as possible. Their connectome
      evolves over 10,000s of generations. We evaluate their circuit complexity, using
      four information-theoretical measures, including one that emphasizes the extent
      to which any network is an irreducible entity. We find that their minimal
      complexity increases with their fitness. 

PMID- 23874169
TI  - Target essentiality and centrality characterize drug side effects.
AB  - To investigate factors contributing to drug side effects, we systematically
      examine relationships between 4,199 side effects associated with 996 drugs and
      their 647 human protein targets. We find that it is the number of essential
      targets, not the number of total targets, that determines the side effects of
      corresponding drugs. Furthermore, within the context of a three-dimensional
      interaction network with atomic-resolution interaction interfaces, we find that
      drugs causing more side effects are also characterized by high degree and
      betweenness of their targets and highly shared interaction interfaces on these
      targets. Our findings suggest that both essentiality and centrality of a drug
      target are key factors contributing to side effects and should be taken into
      consideration in rational drug design. 

PMID- 23874170
TI  - Towards predicting the response of a solid tumour to chemotherapy and
      radiotherapy treatments: clinical insights from a computational model.
AB  - In this paper we use a hybrid multiscale mathematical model that incorporates
      both individual cell behaviour through the cell-cycle and the effects of the
      changing microenvironment through oxygen dynamics to study the multiple effects
      of radiation therapy. The oxygenation status of the cells is considered as one of
      the important prognostic markers for determining radiation therapy, as hypoxic
      cells are less radiosensitive. Another factor that critically affects radiation
      sensitivity is cell-cycle regulation. The effects of radiation therapy are
      included in the model using a modified linear quadratic model for the radiation
      damage, incorporating the effects of hypoxia and cell-cycle in determining the
      cell-cycle phase-specific radiosensitivity. Furthermore, after irradiation, an
      individual cell's cell-cycle dynamics are intrinsically modified through the
      activation of pathways responsible for repair mechanisms, often resulting in a
      delay/arrest in the cell-cycle. The model is then used to study various
      combinations of multiple doses of cell-cycle dependent chemotherapies and
      radiation therapy, as radiation may work better by the partial synchronisation of
      cells in the most radiosensitive phase of the cell-cycle. Moreover, using this
      multi-scale model, we investigate the optimum sequencing and scheduling of these
      multi-modality treatments, and the impact of internal and external heterogeneity
      on the spatio-temporal patterning of the distribution of tumour cells and their
      response to different treatment schedules. 

PMID- 23874172
TI  - Shared protein complex subunits contribute to explaining disrupted co-occurrence.
AB  - The gene composition of present-day genomes has been shaped by a complicated
      evolutionary history, resulting in diverse distributions of genes across genomes.
      The pattern of presence and absence of a gene in different genomes is called its
      phylogenetic profile. It has been shown that proteins whose encoding genes have
      highly similar profiles tend to be functionally related: As these genes were
      gained and lost together, their encoded proteins can probably only perform their
      full function if both are present. However, a large proportion of genes encoding
      interacting proteins do not have matching profiles. In this study, we analysed
      one possible reason for this, namely that phylogenetic profiles can be affected
      by multi-functional proteins such as shared subunits of two or more protein
      complexes. We found that by considering triplets of proteins, of which one
      protein is multi-functional, a large fraction of disturbed co-occurrence patterns
      can be explained. 

PMID- 23874171
TI  - The role of multiple marks in epigenetic silencing and the emergence of a stable
      bivalent chromatin state.
AB  - We introduce and analyze a minimal model of epigenetic silencing in budding
      yeast, built upon known biomolecular interactions in the system. Doing so, we
      identify the epigenetic marks essential for the bistability of epigenetic states.
      The model explicitly incorporates two key chromatin marks, namely H4K16
      acetylation and H3K79 methylation, and explores whether the presence of multiple
      marks lead to a qualitatively different systems behavior. We find that having
      both modifications is important for the robustness of epigenetic silencing.
      Besides the silenced and transcriptionally active fate of chromatin, our model
      leads to a novel state with bivalent (i.e., both active and silencing) marks
      under certain perturbations (knock-out mutations, inhibition or enhancement of
      enzymatic activity). The bivalent state appears under several perturbations and
      is shown to result in patchy silencing. We also show that the titration effect,
      owing to a limited supply of silencing proteins, can result in counter-intuitive
      responses. The design principles of the silencing system is systematically
      investigated and disparate experimental observations are assessed within a single
      theoretical framework. Specifically, we discuss the behavior of Sir protein
      recruitment, spreading and stability of silenced regions in commonly-studied
      mutants (e.g., sas2[Formula: see text], dot1[Formula: see text]) illuminating the
      controversial role of Dot1 in the systems biology of yeast silencing. 

PMID- 23874173
TI  - A model for the self-organization of vesicular flux and protein distributions in
      the Golgi apparatus.
AB  - The generation of two non-identical membrane compartments via exchange of
      vesicles is considered to require two types of vesicles specified by distinct
      cytosolic coats that selectively recruit cargo, and two membrane-bound SNARE
      pairs that specify fusion and differ in their affinities for each type of
      vesicles. The mammalian Golgi complex is composed of 6-8 non-identical cisternae
      that undergo gradual maturation and replacement yet features only two SNARE
      pairs. We present a model that explains how distinct composition of Golgi
      cisternae can be generated with two and even a single SNARE pair and one vesicle
      coat. A decay of active SNARE concentration in aging cisternae provides the seed
      for a cis[Formula: see text]trans SNARE gradient that generates the predominantly
      retrograde vesicle flux which further enhances the gradient. This flux in turn
      yields the observed inhomogeneous steady-state distribution of Golgi enzymes,
      which compete with each other and with the SNAREs for incorporation into
      transport vesicles. We show analytically that the steady state SNARE
      concentration decays exponentially with the cisterna number. Numerical solutions
      of rate equations reproduce the experimentally observed SNARE gradients,
      overlapping enzyme peaks in cis, medial and trans and the reported change in
      vesicle nature across the Golgi: Vesicles originating from younger cisternae
      mostly contain Golgi enzymes and SNAREs enriched in these cisternae and
      extensively recycle through the Endoplasmic Reticulum (ER), while the other
      subpopulation of vesicles contains Golgi proteins prevalent in older cisternae
      and hardly reaches the ER. 

PMID- 23874174
TI  - Hierarchical modeling for rare event detection and cell subset alignment across
      flow cytometry samples.
AB  - Flow cytometry is the prototypical assay for multi-parameter single cell
      analysis, and is essential in vaccine and biomarker research for the enumeration
      of antigen-specific lymphocytes that are often found in extremely low frequencies
      (0.1% or less). Standard analysis of flow cytometry data relies on visual
      identification of cell subsets by experts, a process that is subjective and often
      difficult to reproduce. An alternative and more objective approach is the use of
      statistical models to identify cell subsets of interest in an automated fashion.
      Two specific challenges for automated analysis are to detect extremely low
      frequency event subsets without biasing the estimate by pre-processing
      enrichment, and the ability to align cell subsets across multiple data samples
      for comparative analysis. In this manuscript, we develop hierarchical modeling
      extensions to the Dirichlet Process Gaussian Mixture Model (DPGMM) approach we
      have previously described for cell subset identification, and show that the
      hierarchical DPGMM (HDPGMM) naturally generates an aligned data model that
      captures both commonalities and variations across multiple samples. HDPGMM also
      increases the sensitivity to extremely low frequency events by sharing
      information across multiple samples analyzed simultaneously. We validate the
      accuracy and reproducibility of HDPGMM estimates of antigen-specific T cells on
      clinically relevant reference peripheral blood mononuclear cell (PBMC) samples
      with known frequencies of antigen-specific T cells. These cell samples take
      advantage of retrovirally TCR-transduced T cells spiked into autologous PBMC
      samples to give a defined number of antigen-specific T cells detectable by HLA
      peptide multimer binding. We provide open source software that can take advantage
      of both multiple processors and GPU-acceleration to perform the numerically
      demanding computations. We show that hierarchical modeling is a useful
      probabilistic approach that can provide a consistent labeling of cell subsets and
      increase the sensitivity of rare event detection in the context of quantifying
      antigen-specific immune responses. 

PMID- 23874175
TI  - Transcription factor binding profiles reveal cyclic expression of human protein
      coding genes and non-coding RNAs.
AB  - Cell cycle is a complex and highly supervised process that must proceed with
      regulatory precision to achieve successful cellular division. Despite the wide
      application, microarray time course experiments have several limitations in
      identifying cell cycle genes. We thus propose a computational model to predict
      human cell cycle genes based on transcription factor (TF) binding and regulatory
      motif information in their promoters. We utilize ENCODE ChIP-seq data and motif
      information as predictors to discriminate cell cycle against non-cell cycle
      genes. Our results show that both the trans- TF features and the cis- motif
      features are predictive of cell cycle genes, and a combination of the two types
      of features can further improve prediction accuracy. We apply our model to a
      complete list of GENCODE promoters to predict novel cell cycle driving promoters
      for both protein-coding genes and non-coding RNAs such as lincRNAs. We find that
      a similar percentage of lincRNAs are cell cycle regulated as protein-coding
      genes, suggesting the importance of non-coding RNAs in cell cycle division. The
      model we propose here provides not only a practical tool for identifying novel
      cell cycle genes with high accuracy, but also new insights on cell cycle
      regulation by TFs and cis-regulatory elements. 

PMID- 23874176
TI  - Gain control network conditions in early sensory coding.
AB  - Gain control is essential for the proper function of any sensory system. However,
      the precise mechanisms for achieving effective gain control in the brain are
      unknown. Based on our understanding of the existence and strength of connections
      in the insect olfactory system, we analyze the conditions that lead to controlled
      gain in a randomly connected network of excitatory and inhibitory neurons. We
      consider two scenarios for the variation of input into the system. In the first
      case, the intensity of the sensory input controls the input currents to a fixed
      proportion of neurons of the excitatory and inhibitory populations. In the second
      case, increasing intensity of the sensory stimulus will both, recruit an
      increasing number of neurons that receive input and change the input current that
      they receive. Using a mean field approximation for the network activity we derive
      relationships between the parameters of the network that ensure that the overall
      level of activity of the excitatory population remains unchanged for increasing
      intensity of the external stimulation. We find that, first, the main parameters
      that regulate network gain are the probabilities of connections from the
      inhibitory population to the excitatory population and of the connections within
      the inhibitory population. Second, we show that strict gain control is not
      achievable in a random network in the second case, when the input recruits an
      increasing number of neurons. Finally, we confirm that the gain control
      conditions derived from the mean field approximation are valid in simulations of
      firing rate models and Hodgkin-Huxley conductance based models. 

PMID- 23874177
TI  - Charles Bonnet syndrome: evidence for a generative model in the cortex?
AB  - Several theories propose that the cortex implements an internal model to explain,
      predict, and learn about sensory data, but the nature of this model is unclear.
      One condition that could be highly informative here is Charles Bonnet syndrome
      (CBS), where loss of vision leads to complex, vivid visual hallucinations of
      objects, people, and whole scenes. CBS could be taken as indication that there is
      a generative model in the brain, specifically one that can synthesise rich,
      consistent visual representations even in the absence of actual visual input. The
      processes that lead to CBS are poorly understood. Here, we argue that a model
      recently introduced in machine learning, the deep Boltzmann machine (DBM), could
      capture the relevant aspects of (hypothetical) generative processing in the
      cortex. The DBM carries both the semantics of a probabilistic generative model
      and of a neural network. The latter allows us to model a concrete neural
      mechanism that could underlie CBS, namely, homeostatic regulation of neuronal
      activity. We show that homeostatic plasticity could serve to make the learnt
      internal model robust against e.g. degradation of sensory input, but
      overcompensate in the case of CBS, leading to hallucinations. We demonstrate how
      a wide range of features of CBS can be explained in the model and suggest a
      potential role for the neuromodulator acetylcholine. This work constitutes the
      first concrete computational model of CBS and the first application of the DBM as
      a model in computational neuroscience. Our results lend further credence to the
      hypothesis of a generative model in the brain. 

PMID- 23874178
TI  - Genetic selection for context-dependent stochastic phenotypes: Sp1 and TATA
      mutations increase phenotypic noise in HIV-1 gene expression.
AB  - The sequence of a promoter within a genome does not uniquely determine gene
      expression levels and their variability; rather, promoter sequence can
      additionally interact with its location in the genome, or genomic context, to
      shape eukaryotic gene expression. Retroviruses, such as human immunodeficiency
      virus-1 (HIV), integrate their genomes into those of their host and thereby
      provide a biomedically-relevant model system to quantitatively explore the
      relationship between promoter sequence, genomic context, and noise-driven
      variability on viral gene expression. Using an in vitro model of the HIV Tat
      mediated positive-feedback loop, we previously demonstrated that fluctuations in
      viral Tat-transactivating protein levels generate integration-site-dependent,
      stochastically-driven phenotypes, in which infected cells randomly 'switch'
      between high and low expressing states in a manner that may be related to viral
      latency. Here we extended this model and designed a forward genetic screen to
      systematically identify genetic elements in the HIV LTR promoter that modulate
      the fraction of genomic integrations that specify 'Switching' phenotypes. Our
      screen identified mutations in core promoter regions, including Sp1 and TATA
      transcription factor binding sites, which increased the Switching fraction
      several fold. By integrating single-cell experiments with computational modeling,
      we further investigated the mechanism of Switching-fraction enhancement for a
      selected Sp1 mutation. Our experimental observations demonstrated that the Sp1
      mutation both impaired Tat-transactivated expression and also altered basal
      expression in the absence of Tat. Computational analysis demonstrated that the
      observed change in basal expression could contribute significantly to the
      observed increase in viral integrations that specify a Switching phenotype,
      provided that the selected mutation affected Tat-mediated noise amplification
      differentially across genomic contexts. Our study thus demonstrates a methodology
      to identify and characterize promoter elements that affect the distribution of
      stochastic phenotypes over genomic contexts, and advances our understanding of
      how promoter mutations may control the frequency of latent HIV infection. 

PMID- 23874179
TI  - New universal rules of eukaryotic translation initiation fidelity.
AB  - The accepted model of eukaryotic translation initiation begins with the scanning
      of the transcript by the pre-initiation complex from the 5'end until an ATG codon
      with a specific nucleotide (nt) context surrounding it is recognized (Kozak
      rule). According to this model, ATG codons upstream to the beginning of the ORF
      should affect translation. We perform for the first time, a genome-wide
      statistical analysis, uncovering a new, more comprehensive and quantitative, set
      of initiation rules for improving the cost of translation and its efficiency.
      Analyzing dozens of eukaryotic genomes, we find that in all frames there is a
      universal trend of selection for low numbers of ATG codons; specifically, 16-27
      codons upstream, but also 5-11 codons downstream of the START ATG, include less
      ATG codons than expected. We further suggest that there is selection for anti
      optimal ATG contexts in the vicinity of the START ATG. Thus, the efficiency and
      fidelity of translation initiation is encoded in the 5'UTR as required by the
      scanning model, but also at the beginning of the ORF. The observed nt patterns
      suggest that in all the analyzed organisms the pre-initiation complex often
      misses the START ATG of the ORF, and may start translation from an alternative
      initiation start-site. Thus, to prevent the translation of undesired proteins,
      there is selection for nucleotide sequences with low affinity to the pre
      initiation complex near the beginning of the ORF. With the new suggested rules we
      were able to obtain a twice higher correlation with ribosomal density and protein
      levels in comparison to the Kozak rule alone (e.g. for protein levels r=0.7 vs.
      r=0.31; p<10(-12)).

PMID- 23874180
TI  - Frequency dependence of signal power and spatial reach of the local field
      potential.
AB  - Despite its century-old use, the interpretation of local field potentials (LFPs),
      the low-frequency part of electrical signals recorded in the brain, is still
      debated. In cortex the LFP appears to mainly stem from transmembrane neuronal
      currents following synaptic input, and obvious questions regarding the 'locality'
      of the LFP are: What is the size of the signal-generating region, i.e., the
      spatial reach, around a recording contact? How far does the LFP signal extend
      outside a synaptically activated neuronal population? And how do the answers
      depend on the temporal frequency of the LFP signal? Experimental inquiries have
      given conflicting results, and we here pursue a modeling approach based on a well
      established biophysical forward-modeling scheme incorporating detailed
      reconstructed neuronal morphologies in precise calculations of population LFPs
      including thousands of neurons. The two key factors determining the frequency
      dependence of LFP are the spatial decay of the single-neuron LFP contribution and
      the conversion of synaptic input correlations into correlations between single
      neuron LFP contributions. Both factors are seen to give low-pass filtering of the
      LFP signal power. For uncorrelated input only the first factor is relevant, and
      here a modest reduction (<50%) in the spatial reach is observed for higher
      frequencies (>100 Hz) compared to the near-DC ([Formula: see text]) value of
      about [Formula: see text]. Much larger frequency-dependent effects are seen when
      populations of pyramidal neurons receive correlated and spatially asymmetric
      inputs: the low-frequency ([Formula: see text]) LFP power can here be an order of
      magnitude or more larger than at 60 Hz. Moreover, the low-frequency LFP
      components have larger spatial reach and extend further outside the active
      population than high-frequency components. Further, the spatial LFP profiles for
      such populations typically span the full vertical extent of the dendrites of
      neurons in the population. Our numerical findings are backed up by an intuitive
      simplified model for the generation of population LFP. 

PMID- 23874182
TI  - Distinct allelic patterns of nanog expression impart embryonic stem cell
      population heterogeneity.
AB  - Nanog is a principal pluripotency regulator exhibiting a disperse distribution
      within stem cell populations in vivo and in vitro. Increasing evidence points to
      a functional role of Nanog heterogeneity on stem cell fate decisions. Allelic
      control of Nanog gene expression was reported recently in mouse embryonic stem
      cells. To better understand how this mode of regulation influences the observed
      heterogeneity of NANOG in stem cell populations, we assembled a multiscale
      stochastic population balance equation framework. In addition to allelic control,
      gene expression noise and random partitioning at cell division were considered.
      As a result of allelic Nanog expression, the distribution of Nanog exhibited
      three distinct states but when combined with transcriptional noise the profile
      became bimodal. Regardless of their allelic expression pattern, initially uniform
      populations of stem cells gave rise to the same Nanog heterogeneity within ten
      cell cycles. Depletion of NANOG content in cells switching off both gene alleles
      was slower than the accumulation of intracellular NANOG after cells turned on at
      least one of their Nanog gene copies pointing to Nanog state-dependent dynamics.
      Allelic transcription of Nanog also raises issues regarding the use of stem cell
      lines with reporter genes knocked in a single allelic locus. Indeed, significant
      divergence was observed in the reporter and native protein profiles depending on
      the difference in their half-lives and insertion of the reporter gene in one or
      both alleles. In stem cell populations with restricted Nanog expression, allelic
      regulation facilitates the maintenance of fractions of self-renewing cells with
      sufficient Nanog content to prevent aberrant loss of pluripotency. Our findings
      underline the role of allelic control of Nanog expression as a prime determinant
      of stem cell population heterogeneity and warrant further investigation in the
      contexts of stem cell specification and cell reprogramming. 

PMID- 23874181
TI  - Successful reconstruction of a physiological circuit with known connectivity from
      spiking activity alone.
AB  - Identifying the structure and dynamics of synaptic interactions between neurons
      is the first step to understanding neural network dynamics. The presence of
      synaptic connections is traditionally inferred through the use of targeted
      stimulation and paired recordings or by post-hoc histology. More recently, causal
      network inference algorithms have been proposed to deduce connectivity directly
      from electrophysiological signals, such as extracellularly recorded spiking
      activity. Usually, these algorithms have not been validated on a
      neurophysiological data set for which the actual circuitry is known. Recent work
      has shown that traditional network inference algorithms based on linear models
      typically fail to identify the correct coupling of a small central pattern
      generating circuit in the stomatogastric ganglion of the crab Cancer borealis. In
      this work, we show that point process models of observed spike trains can guide
      inference of relative connectivity estimates that match the known physiological
      connectivity of the central pattern generator up to a choice of threshold. We
      elucidate the necessary steps to derive faithful connectivity estimates from a
      model that incorporates the spike train nature of the data. We then apply the
      model to measure changes in the effective connectivity pattern in response to two
      pharmacological interventions, which affect both intrinsic neural dynamics and
      synaptic transmission. Our results provide the first successful application of a
      network inference algorithm to a circuit for which the actual physiological
      synapses between neurons are known. The point process methodology presented here
      generalizes well to larger networks and can describe the statistics of neural
      populations. In general we show that advanced statistical models allow for the
      characterization of effective network structure, deciphering underlying network
      dynamics and estimating information-processing capabilities. 

PMID- 23874183
TI  - Dynamic fluctuations provide the basis of a conformational switch mechanism in
      apo cyclic AMP receptor protein.
AB  - Escherichia coli cyclic AMP Receptor Protein (CRP) undergoes conformational
      changes with cAMP binding and allosterically promotes CRP to bind specifically to
      the DNA. In that, the structural and dynamic properties of apo CRP prior to cAMP
      binding are of interest for the comprehension of the activation mechanism. Here,
      the dynamics of apo CRP monomer/dimer and holo CRP dimer were studied by
      Molecular Dynamics (MD) simulations and Gaussian Network Model (GNM). The
      interplay of the inter-domain hinge with the cAMP and DNA binding domains are pre
      disposed in the apo state as a conformational switch in the CRP's allosteric
      communication mechanism. The hinge at L134-D138 displaying intra- and inter
      subunit coupled fluctuations with the cAMP and DNA binding domains leads to the
      emergence of stronger coupled fluctuations between the two domains and describes
      an on state. The flexible regions at K52-E58, P154/D155 and I175 maintain the
      dynamic coupling of the two domains. With a shift in the inter-domain hinge
      position towards the N terminus, nevertheless, the latter correlations between
      the domains loosen and become disordered; L134-D138 dynamically interacts only
      with the cAMP and DNA binding domains of its own subunit, and an off state is
      assumed. We present a mechanistic view on how the structural dynamic units are
      hierarchically built for the allosteric functional mechanism; from apo CRP
      monomer to apo-to-holo CRP dimers. 

PMID- 23874184
TI  - Epidemiologically optimal static networks from temporal network data.
AB  - One of network epidemiology's central assumptions is that the contact structure
      over which infectious diseases propagate can be represented as a static network.
      However, contacts are highly dynamic, changing at many time scales. In this
      paper, we investigate conceptually simple methods to construct static graphs for
      network epidemiology from temporal contact data. We evaluate these methods on
      empirical and synthetic model data. For almost all our cases, the network
      representation that captures most relevant information is a so-called exponential
      threshold network. In these, each contact contributes with a weight decreasing
      exponentially with time, and there is an edge between a pair of vertices if the
      weight between them exceeds a threshold. Networks of aggregated contacts over an
      optimally chosen time window perform almost as good as the exponential-threshold
      networks. On the other hand, networks of accumulated contacts over the entire
      sampling time, and networks of concurrent partnerships, perform worse. We discuss
      these observations in the context of the temporal and topological structure of
      the data sets. 

PMID- 23874185
TI  - Inferring nonlinear neuronal computation based on physiologically plausible
      inputs.
AB  - The computation represented by a sensory neuron's response to stimuli is
      constructed from an array of physiological processes both belonging to that
      neuron and inherited from its inputs. Although many of these physiological
      processes are known to be nonlinear, linear approximations are commonly used to
      describe the stimulus selectivity of sensory neurons (i.e., linear receptive
      fields). Here we present an approach for modeling sensory processing, termed the
      Nonlinear Input Model (NIM), which is based on the hypothesis that the dominant
      nonlinearities imposed by physiological mechanisms arise from rectification of a
      neuron's inputs. Incorporating such 'upstream nonlinearities' within the standard
      linear-nonlinear (LN) cascade modeling structure implicitly allows for the
      identification of multiple stimulus features driving a neuron's response, which
      become directly interpretable as either excitatory or inhibitory. Because its
      form is analogous to an integrate-and-fire neuron receiving excitatory and
      inhibitory inputs, model fitting can be guided by prior knowledge about the
      inputs to a given neuron, and elements of the resulting model can often result in
      specific physiological predictions. Furthermore, by providing an explicit
      probabilistic model with a relatively simple nonlinear structure, its parameters
      can be efficiently optimized and appropriately regularized. Parameter estimation
      is robust and efficient even with large numbers of model components and in the
      context of high-dimensional stimuli with complex statistical structure (e.g.
      natural stimuli). We describe detailed methods for estimating the model
      parameters, and illustrate the advantages of the NIM using a range of example
      sensory neurons in the visual and auditory systems. We thus present a modeling
      framework that can capture a broad range of nonlinear response functions while
      providing physiologically interpretable descriptions of neural computation. 

PMID- 23874186
TI  - Structural disorder provides increased adaptability for vesicle trafficking
      pathways.
AB  - Vesicle trafficking systems play essential roles in the communication between the
      organelles of eukaryotic cells and also between cells and their environment.
      Endocytosis and the late secretory route are mediated by clathrin-coated
      vesicles, while the COat Protein I and II (COPI and COPII) routes stand for the
      bidirectional traffic between the ER and the Golgi apparatus. Despite similar
      fundamental organizations, the molecular machinery, functions, and evolutionary
      characteristics of the three systems are very different. In this work, we
      compiled the basic functional protein groups of the three main routes for human
      and yeast and analyzed them from the structural disorder perspective. We found
      similar overall disorder content in yeast and human proteins, confirming the well
      conserved nature of these systems. Most functional groups contain highly
      disordered proteins, supporting the general importance of structural disorder in
      these routes, although some of them seem to heavily rely on disorder, while
      others do not. Interestingly, the clathrin system is significantly more
      disordered (~23%) than the other two, COPI (~9%) and COPII (~8%). We show that
      this structural phenomenon enhances the inherent plasticity and increased
      evolutionary adaptability of the clathrin system, which distinguishes it from the
      other two routes. Since multi-functionality (moonlighting) is indicative of both
      plasticity and adaptability, we studied its prevalence in vesicle trafficking
      proteins and correlated it with structural disorder. Clathrin adaptors have the
      highest capability for moonlighting while also comprising the most highly
      disordered members. The ability to acquire tissue specific functions was also
      used to approach adaptability: clathrin route genes have the most tissue specific
      exons encoding for protein segments enriched in structural disorder and
      interaction sites. Overall, our results confirm the general importance of
      structural disorder in vesicle trafficking and suggest major roles for this
      structural property in shaping the differences of evolutionary adaptability in
      the three routes.

PMID- 23874187
TI  - Statistical analysis of molecular signal recording.
AB  - A molecular device that records time-varying signals would enable new approaches
      in neuroscience. We have recently proposed such a device, termed a "molecular
      ticker tape", in which an engineered DNA polymerase (DNAP) writes time-varying
      signals into DNA in the form of nucleotide misincorporation patterns. Here, we
      define a theoretical framework quantifying the expected capabilities of molecular
      ticker tapes as a function of experimental parameters. We present a decoding
      algorithm for estimating time-dependent input signals, and DNAP kinetic
      parameters, directly from misincorporation rates as determined by sequencing. We
      explore the requirements for accurate signal decoding, particularly the
      constraints on (1) the polymerase biochemical parameters, and (2) the amplitude,
      temporal resolution, and duration of the time-varying input signals. Our results
      suggest that molecular recording devices with kinetic properties similar to
      natural polymerases could be used to perform experiments in which neural activity
      is compared across several experimental conditions, and that devices engineered
      by combining favorable biochemical properties from multiple known polymerases
      could potentially measure faster phenomena such as slow synchronization of
      neuronal oscillations. Sophisticated engineering of DNAPs is likely required to
      achieve molecular recording of neuronal activity with single-spike temporal
      resolution over experimentally relevant timescales. 

PMID- 23874189
TI  - Ten simple rules for writing a literature review.

PMID- 23874188
TI  - Dynamics of SIN asymmetry establishment.
AB  - Timing of cell division is coordinated by the Septation Initiation Network (SIN)
      in fission yeast. SIN activation is initiated at the two spindle pole bodies
      (SPB) of the cell in metaphase, but only one of these SPBs contains an active SIN
      in anaphase, while SIN is inactivated in the other by the Cdc16-Byr4 GAP complex.
      Most of the factors that are needed for such asymmetry establishment have been
      already characterized, but we lack the molecular details that drive such quick
      asymmetric distribution of molecules at the two SPBs. Here we investigate the
      problem by computational modeling and, after establishing a minimal system with
      two antagonists that can drive reliable asymmetry establishment, we incorporate
      the current knowledge on the basic SIN regulators into an extended model with
      molecular details of the key regulators. The model can capture several peculiar
      earlier experimental findings and also predicts the behavior of double and triple
      SIN mutants. We experimentally tested one prediction, that phosphorylation of the
      scaffold protein Cdc11 by a SIN kinase and the core cell cycle regulatory Cyclin
      dependent kinase (Cdk) can compensate for mutations in the SIN inhibitor Cdc16
      with different efficiencies. One aspect of the prediction failed, highlighting a
      potential hole in our current knowledge. Further experimental tests revealed that
      SIN induced Cdc11 phosphorylation might have two separate effects. We conclude
      that SIN asymmetry is established by the antagonistic interactions between SIN
      and its inhibitor Cdc16-Byr4, partially through the regulation of Cdc11
      phosphorylation states. 

PMID- 23874190
TI  - Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective
      chemotherapy with application to the current generation of antimalarial drugs.
AB  - Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD) modelling is the standard
      computational technique for simulating drug treatment of infectious diseases with
      the potential to enhance our understanding of drug treatment outcomes, drug
      deployment strategies, and dosing regimens. Standard methodologies assume only a
      single drug is used, it acts only in its unconverted form, and that oral drugs
      are instantaneously absorbed across the gut wall to their site of action. For
      drugs with short half-lives, this absorption period accounts for a significant
      period of their time in the body. Treatment of infectious diseases often uses
      combination therapies, so we refined and substantially extended the PK/PD
      methodologies to incorporate (i) time lags and drug concentration profiles
      resulting from absorption across the gut wall and, if required, conversion to
      another active form; (ii) multiple drugs within a treatment combination; (iii)
      differing modes of action of drugs in the combination: additive, synergistic,
      antagonistic; (iv) drugs converted to an active metabolite with a similar mode of
      action. This methodology was applied to a case study of two first-line malaria
      treatments based on artemisinin combination therapies (ACTs, artemether
      lumefantrine and artesunate-mefloquine) where the likelihood of increased
      artemisinin tolerance/resistance has led to speculation on their continued long
      term effectiveness. We note previous estimates of artemisinin kill rate were
      underestimated by a factor of seven, both the unconverted and converted form of
      the artemisinins kill parasites and the extended PK/PD methodology produced
      results consistent with field observations. The simulations predict that a
      potentially rapid decline in ACT effectiveness is likely to occur as artemisinin
      resistance spreads, emphasising the importance of containing the spread of
      artemisinin resistance before it results in widespread drug failure. We found
      that PK/PD data is generally very poorly reported in the malaria literature,
      severely reducing its value for subsequent re-application, and we make specific
      recommendations to improve this situation. 

PMID- 23874191
TI  - GEMINI: integrative exploration of genetic variation and genome annotations.
AB  - Modern DNA sequencing technologies enable geneticists to rapidly identify genetic
      variation among many human genomes. However, isolating the minority of variants
      underlying disease remains an important, yet formidable challenge for medical
      genetics. We have developed GEMINI (GEnome MINIng), a flexible software package
      for exploring all forms of human genetic variation. Unlike existing tools, GEMINI
      integrates genetic variation with a diverse and adaptable set of genome
      annotations (e.g., dbSNP, ENCODE, UCSC, ClinVar, KEGG) into a unified database to
      facilitate interpretation and data exploration. Whereas other methods provide an
      inflexible set of variant filters or prioritization methods, GEMINI allows
      researchers to compose complex queries based on sample genotypes, inheritance
      patterns, and both pre-installed and custom genome annotations. GEMINI also
      provides methods for ad hoc queries and data exploration, a simple programming
      interface for custom analyses that leverage the underlying database, and both
      command line and graphical tools for common analyses. We demonstrate GEMINI's
      utility for exploring variation in personal genomes and family based genetic
      studies, and illustrate its ability to scale to studies involving thousands of
      human samples. GEMINI is designed for reproducibility and flexibility and our
      goal is to provide researchers with a standard framework for medical genomics. 

PMID- 23874192
TI  - A systematic framework for molecular dynamics simulations of protein post
      translational modifications.
AB  - By directly affecting structure, dynamics and interaction networks of their
      targets, post-translational modifications (PTMs) of proteins play a key role in
      different cellular processes ranging from enzymatic activation to regulation of
      signal transduction to cell-cycle control. Despite the great importance of
      understanding how PTMs affect proteins at the atomistic level, a systematic
      framework for treating post-translationally modified amino acids by molecular
      dynamics (MD) simulations, a premier high-resolution computational biology tool,
      has never been developed. Here, we report and validate force field parameters
      (GROMOS 45a3 and 54a7) required to run and analyze MD simulations of more than
      250 different types of enzymatic and non-enzymatic PTMs. The newly developed
      GROMOS 54a7 parameters in particular exhibit near chemical accuracy in matching
      experimentally measured hydration free energies (RMSE=4.2 kJ/mol over the
      validation set). Using this tool, we quantitatively show that the majority of
      PTMs greatly alter the hydrophobicity and other physico-chemical properties of
      target amino acids, with the extent of change in many cases being comparable to
      the complete range spanned by native amino acids.

PMID- 23874193
TI  - Variations within class-A beta-lactamase physiochemical properties reflect
      evolutionary and environmental patterns, but not antibiotic specificity.
AB  - The bacterial enzyme beta-lactamase hydrolyzes the beta-lactam ring of penicillin
      and chemically related antibiotics, rendering them ineffective. Due to rampant
      antibiotic overuse, the enzyme is evolving new resistance activities at an
      alarming rate. Related, the enzyme's global physiochemical properties exhibit
      various amounts of conservation and variability across the family. To that end,
      we characterize the extent of property conservation within twelve different class
      A beta-lactamases, and conclusively establish that the systematic variations
      therein parallel their evolutionary history. Large and systematic differences
      within electrostatic potential maps and pairwise residue-to-residue couplings are
      observed across the protein, which robustly reflect phylogenetic outgroups. Other
      properties are more conserved (such as residue pKa values, electrostatic
      networks, and backbone flexibility), yet they also have systematic variations
      that parallel the phylogeny in a statistically significant way. Similarly, the
      above properties also parallel the environmental condition of the bacteria they
      are from in a statistically significant way. However, it is interesting and
      surprising that the only one of the global properties (protein charge) parallels
      the functional specificity patterns; meaning antibiotic resistance activities are
      not significantly constraining the global physiochemical properties. Rather,
      extended spectrum activities can emerge from the background of nearly any set of
      electrostatic and dynamic properties. 

PMID- 23874195
TI  - It's no fluke: the planarian as a model for understanding schistosomes.

PMID- 23874194
TI  - Expanding the druggable space of the LSD1/CoREST epigenetic target: new potential
      binding regions for drug-like molecules, peptides, protein partners, and
      chromatin.
AB  - Lysine specific demethylase-1 (LSD1/KDM1A) in complex with its corepressor
      protein CoREST is a promising target for epigenetic drugs. No therapeutic that
      targets LSD1/CoREST, however, has been reported to date. Recently, extended
      molecular dynamics (MD) simulations indicated that LSD1/CoREST nanoscale clamp
      dynamics is regulated by substrate binding and highlighted key hinge points of
      this large-scale motion as well as the relevance of local residue dynamics.
      Prompted by the urgent need for new molecular probes and inhibitors to understand
      LSD1/CoREST interactions with small-molecules, peptides, protein partners, and
      chromatin, we undertake here a configurational ensemble approach to expand
      LSD1/CoREST druggability. The independent algorithms FTMap and SiteMap and our
      newly developed Druggable Site Visualizer (DSV) software tool were used to
      predict and inspect favorable binding sites. We find that the hinge points
      revealed by MD simulations at the SANT2/Tower interface, at the SWIRM/AOD
      interface, and at the AOD/Tower interface are new targets for the discovery of
      molecular probes to block association of LSD1/CoREST with chromatin or protein
      partners. A fourth region was also predicted from simulated configurational
      ensembles and was experimentally validated to have strong binding propensity. The
      observation that this prediction would be prevented when using only the X-ray
      structures available (including the X-ray structure bound to the same peptide)
      underscores the relevance of protein dynamics in protein interactions. A fifth
      region was highlighted corresponding to a small pocket on the AOD domain. This
      study sets the basis for future virtual screening campaigns targeting the five
      novel regions reported herein and for the design of LSD1/CoREST mutants to probe
      LSD1/CoREST binding with chromatin and various protein partners. 

PMID- 23874196
TI  - Tripping on acid: trans-kingdom perspectives on biological acids in immunity and
      pathogenesis.

PMID- 23874197
TI  - HIF-1alpha is essential for effective PMN bacterial killing, antimicrobial
      peptide production and apoptosis in Pseudomonas aeruginosa keratitis.
AB  - Hypoxia-inducible factor (HIF)-1alpha, is a transcription factor that controls
      energy metabolism and angiogenesis under hypoxic conditions, and a potent
      regulator of innate immunity. The studies described herein examined the role of
      HIF-1alpha in disease resolution in BALB/c (resistant, cornea heals) mice after
      ocular infection with Pseudomonas (P.) aeruginosa. Furthermore, the current
      studies focused on the neutrophil (PMN), the predominant cell infiltrate in
      keratitis. Using both siRNA and an antagonist (17-DMAG), the role of HIF-1alpha
      was assessed in P. aeruginosa-infected BALB/c mice. Clinical score and slit lamp
      photography indicated HIF-1alpha inhibition exacerbated disease and corneal
      destruction. Real time RT-PCR, immunohistochemistry, ELISA, Greiss and MPO
      assays, bacterial load, intracellular killing, phagocytosis and apoptosis assays
      further tested the regulatory role of HIF-1alpha. Despite increased pro
      inflammatory cytokine expression and increased MPO levels after knocking down HIF
      1alpha expression, in vivo studies revealed a decrease in NO production and
      higher bacterial load. In vitro studies using PMN provided evidence that although
      inhibition of HIF-1alpha did not affect phagocytosis, both bacterial killing and
      apoptosis were significantly affected, as was production of antimicrobial
      peptides. Overall, data provide evidence that inhibition of HIF-1alpha converts a
      normally resistant disease response to susceptible (corneal thinning and
      perforation) after induction of bacterial keratitis. Although this inhibition
      does not appear to affect PMN transmigration or phagocytosis, both in vivo and in
      vitro approaches indicate that the transcriptional factor is essential for
      effective bacterial killing, apoptosis and antimicrobial peptide production. 

PMID- 23874198
TI  - Endothelial cell permeability during hantavirus infection involves factor XII
      dependent increased activation of the kallikrein-kinin system.
AB  - Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome
      (HPS) are diseases caused by hantavirus infections and are characterized by
      vascular leakage due to alterations of the endothelial barrier. Hantavirus
      infected endothelial cells (EC) display no overt cytopathology; consequently,
      pathogenesis models have focused either on the influx of immune cells and release
      of cytokines or on increased degradation of the adherens junction protein,
      vascular endothelial (VE)-cadherin, due to hantavirus-mediated hypersensitization
      of EC to vascular endothelial growth factor (VEGF). To examine endothelial
      leakage in a relevant in vitro system, we co-cultured endothelial and vascular
      smooth muscle cells (vSMC) to generate capillary blood vessel-like structures. In
      contrast to results obtained in monolayers of cultured EC, we found that despite
      viral replication in both cell types as well as the presence of VEGF, infected in
      vitro vessels neither lost integrity nor displayed evidence of VE-cadherin
      degradation. Here, we present evidence for a novel mechanism of hantavirus
      induced vascular leakage involving activation of the plasma kallikrein-kinin
      system (KKS). We show that incubation of factor XII (FXII), prekallikrein (PK),
      and high molecular weight kininogen (HK) plasma proteins with hantavirus-infected
      EC results in increased cleavage of HK, higher enzymatic activities of
      FXIIa/kallikrein (KAL) and increased liberation of bradykinin (BK). Measuring
      cell permeability in real-time using electric cell-substrate impedance sensing
      (ECIS), we identified dramatic increases in endothelial cell permeability after
      KKS activation and liberation of BK. Furthermore, the alterations in permeability
      could be prevented using inhibitors that directly block BK binding, the activity
      of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is
      increased on the surface of hantavirus-infected EC. These data are the first to
      demonstrate KKS activation during hantavirus infection and could have profound
      implications for treatment of hantavirus infections. 

PMID- 23874199
TI  - Negative regulation of type I IFN expression by OASL1 permits chronic viral
      infection and CD8+ T-cell exhaustion.
AB  - The type I interferons (IFN-Is) are critical not only in early viral control but
      also in prolonged T-cell immune responses. However, chronic viral infections such
      as those of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in
      humans and lymphocytic choriomeningitis virus (LCMV) in mice overcome this early
      IFN-I barrier and induce viral persistence and exhaustion of T-cell function.
      Although various T-cell-intrinsic and -extrinsic factors are known to contribute
      to induction of chronic conditions, the roles of IFN-I negative regulators in
      chronic viral infections have been largely unexplored. Herein, we explored
      whether 2'-5' oligoadenylate synthetase-like 1 (OASL1), a recently defined IFN-I
      negative regulator, plays a key role in the virus-specific T-cell response and
      viral defense against chronic LCMV. To this end, we infected Oasl1 knockout and
      wild-type mice with LCMV CL-13 (a chronic virus) and monitored T-cell responses,
      serum cytokine levels, and viral titers. LCMV CL-13-infected Oasl1 KO mice
      displayed a sustained level of serum IFN-I, which was primarily produced by
      splenic plasmacytoid dendritic cells, during the very early phase of infection (2
      3 days post-infection). Oasl1 deficiency also led to the accelerated elimination
      of viremia and induction of a functional antiviral CD8 T-cell response, which
      critically depended on IFN-I receptor signaling. Together, these results
      demonstrate that OASL1-mediated negative regulation of IFN-I production at an
      early phase of infection permits viral persistence and suppresses T-cell
      function, suggesting that IFN-I negative regulators, including OASL1, could be
      exciting new targets for preventing chronic viral infection. 

PMID- 23874200
TI  - Mechanism of HIV-1 virion entrapment by tetherin.
AB  - Tetherin, an interferon-inducible membrane protein, inhibits the release of
      nascent enveloped viral particles from the surface of infected cells. However,
      the mechanisms underlying virion retention have not yet been fully delineated.
      Here, we employ biochemical assays and engineered tetherin proteins to
      demonstrate conclusively that virion tethers are composed of the tetherin protein
      itself, and to elucidate the configuration and topology that tetherin adopts
      during virion entrapment. We demonstrate that tetherin dimers adopt an "axial"
      configuration, in which pairs of transmembrane domains or pairs of
      glycosylphosphatidyl inositol anchors are inserted into assembling virion
      particles, while the remaining pair of membrane anchors remains embedded in the
      infected cell membrane. We use quantitative western blotting to determine that a
      few dozen tetherin dimers are used to tether each virion particle, and that there
      is ~3- to 5-fold preference for the insertion of glycosylphosphatidyl inositol
      anchors rather than transmembrane domains into tethered virions. Cumulatively,
      these results demonstrate that axially configured tetherin homodimers are
      directly responsible for trapping virions at the cell surface. We suggest that
      insertion of glycosylphosphatidyl inositol anchors may be preferred so that
      effector functions that require exposure of the tetherin N-terminus to the
      cytoplasm of infected cells are retained. 

PMID- 23874201
TI  - Systemically circulating viral and tumor-derived microRNAs in KSHV-associated
      malignancies.
AB  - MicroRNAs (miRNAs) are stable, small non-coding RNAs that modulate many
      downstream target genes. Recently, circulating miRNAs have been detected in
      various body fluids and within exosomes, prompting their evaluation as candidate
      biomarkers of diseases, especially cancer. Kaposi's sarcoma (KS) is the most
      common AIDS-associated cancer and remains prevalent despite Highly Active Anti
      Retroviral Therapy (HAART). KS is caused by KS-associated herpesvirus (KSHV), a
      gamma herpesvirus also associated with Primary Effusion Lymphoma (PEL). We sought
      to determine the host and viral circulating miRNAs in plasma, pleural fluid or
      serum from patients with the KSHV-associated malignancies KS and PEL and from two
      mouse models of KS. Both KSHV-encoded miRNAs and host miRNAs, including members
      of the miR-17-92 cluster, were detectable within patient exosomes and circulating
      miRNA profiles from KSHV mouse models. Further characterization revealed a subset
      of miRNAs that seemed to be preferentially incorporated into exosomes. Gene
      ontology analysis of signature exosomal miRNA targets revealed several signaling
      pathways that are known to be important in KSHV pathogenesis. Functional analysis
      of endothelial cells exposed to patient-derived exosomes demonstrated enhanced
      cell migration and IL-6 secretion. This suggests that exosomes derived from KSHV
      associated malignancies are functional and contain a distinct subset of miRNAs.
      These could represent candidate biomarkers of disease and may contribute to the
      paracrine phenotypes that are a characteristic of KS. 

PMID- 23874202
TI  - Evolutionary toggling of Vpx/Vpr specificity results in divergent recognition of
      the restriction factor SAMHD1.
AB  - SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such
      as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells.
      This restriction is alleviated by expression of the lentiviral accessory proteins
      Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation.
      However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain
      unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has
      caused the interface between SAMHD1 and Vpx/Vpr to alter during primate
      lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx
      from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm
      lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and
      degradation. On the other hand, the N-terminus of SAMHD1 governs interactions
      with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and
      SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is
      evolutionarily dynamic, with the importance of the N- and C-terminus for
      interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We
      present a model to explain how the head-to-tail conformation of SAMHD1 proteins
      favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms
      race. Such drastic functional divergence within a lentiviral protein highlights a
      novel plasticity in the evolutionary dynamics of viral antagonists for
      restriction factors during lentiviral adaptation to its hosts. 

PMID- 23874203
TI  - Mycobacterium tuberculosis nucleoside diphosphate kinase inactivates small
      GTPases leading to evasion of innate immunity.
AB  - Defining the mechanisms of Mycobacterium tuberculosis (Mtb) persistence in the
      host macrophage and identifying mycobacterial factors responsible for it are keys
      to better understand tuberculosis pathogenesis. The emerging picture from ongoing
      studies of macrophage deactivation by Mtb suggests that ingested bacilli secrete
      various virulence determinants that alter phagosome biogenesis, leading to arrest
      of Mtb vacuole interaction with late endosomes and lysosomes. While most studies
      focused on Mtb interference with various regulators of the endosomal compartment,
      little attention was paid to mechanisms by which Mtb neutralizes early macrophage
      responses such as the NADPH oxidase (NOX2) dependent oxidative burst. Here we
      applied an antisense strategy to knock down Mtb nucleoside diphosphate kinase
      (Ndk) and obtained a stable mutant (Mtb Ndk-AS) that displayed attenuated
      intracellular survival along with reduced persistence in the lungs of infected
      mice. At the molecular level, pull-down experiments showed that Ndk binds to and
      inactivates the small GTPase Rac1 in the macrophage. This resulted in the
      exclusion of the Rac1 binding partner p67(phox) from phagosomes containing Mtb or
      Ndk-coated latex beads. Exclusion of p67(phox) was associated with a defect of
      both NOX2 assembly and production of reactive oxygen species (ROS) in response to
      wild type Mtb. In contrast, Mtb Ndk-AS, which lost the capacity to disrupt Rac1
      p67(phox) interaction, induced a strong ROS production. Given the established
      link between NOX2 activation and apoptosis, the proportion of Annexin V positive
      cells and levels of intracellular active caspase 3 were significantly higher in
      cells infected with Mtb Ndk-AS compared to wild type Mtb. Thus, knock down of Ndk
      converted Mtb into a pro-apoptotic mutant strain that has a phenotype of
      increased susceptibility to intracellular killing and reduced virulence in vivo.
      Taken together, our in vitro and in vivo data revealed that Ndk contributes
      significantly to Mtb virulence via attenuation of NADPH oxidase-mediated host
      innate immunity. 

PMID- 23874204
TI  - The footprint of genome architecture in the largest genome expansion in RNA
      viruses.
AB  - The small size of RNA virus genomes (2-to-32 kb) has been attributed to high
      mutation rates during replication, which is thought to lack proof-reading. This
      paradigm is being revisited owing to the discovery of a 3'-to-5' exoribonuclease
      (ExoN) in nidoviruses, a monophyletic group of positive-stranded RNA viruses with
      a conserved genome architecture. ExoN, a homolog of canonical DNA proof-reading
      enzymes, is exclusively encoded by nidoviruses with genomes larger than 20 kb.
      All other known non-segmented RNA viruses have smaller genomes. Here we use
      evolutionary analyses to show that the two- to three-fold expansion of the
      nidovirus genome was accompanied by a large number of replacements in conserved
      proteins at a scale comparable to that in the Tree of Life. To unravel common
      evolutionary patterns in such genetically diverse viruses, we established the
      relation between genomic regions in nidoviruses in a sequence alignment-free
      manner. We exploited the conservation of the genome architecture to partition
      each genome into five non-overlapping regions: 5' untranslated region (UTR), open
      reading frame (ORF) 1a, ORF1b, 3'ORFs (encompassing the 3'-proximal ORFs), and 3'
      UTR. Each region was analyzed for its contribution to genome size change under
      different models. The non-linear model statistically outperformed the linear one
      and captured >92% of data variation. Accordingly, nidovirus genomes were
      concluded to have reached different points on an expansion trajectory dominated
      by consecutive increases of ORF1b, ORF1a, and 3'ORFs. Our findings indicate a
      unidirectional hierarchical relation between these genome regions, which are
      distinguished by their expression mechanism. In contrast, these regions cooperate
      bi-directionally on a functional level in the virus life cycle, in which they
      predominantly control genome replication, genome expression, and virus
      dissemination, respectively. Collectively, our findings suggest that genome
      architecture and the associated region-specific division of labor leave a
      footprint on genome expansion and may limit RNA genome size. 

PMID- 23874205
TI  - Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis.
AB  - Disease progression in response to infection can be strongly influenced by both
      pathogen burden and infection-induced immunopathology. While current therapeutics
      focus on augmenting protective immune responses, identifying therapeutics that
      reduce infection-induced immunopathology are clearly warranted. Despite the
      apparent protective role for murine CD8+ T cells following infection with the
      intracellular parasite Leishmania, CD8+ T cells have been paradoxically linked to
      immunopathological responses in human cutaneous leishmaniasis. Transcriptome
      analysis of lesions from Leishmania braziliensis patients revealed that genes
      associated with the cytolytic pathway are highly expressed and CD8+ T cells from
      lesions exhibited a cytolytic phenotype. To determine if CD8+ T cells play a
      causal role in disease, we turned to a murine model. These studies revealed that
      disease progression and metastasis in L. braziliensis infected mice was
      independent of parasite burden and was instead directly associated with the
      presence of CD8+ T cells. In mice with severe pathology, we visualized CD8+ T
      cell degranulation and lysis of L. braziliensis infected cells. Finally, in
      contrast to wild-type CD8+ T cells, perforin-deficient cells failed to induce
      disease. Thus, we show for the first time that cytolytic CD8+ T cells mediate
      immunopathology and drive the development of metastatic lesions in cutaneous
      leishmaniasis.

PMID- 23874207
TI  - NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic
      mechanisms in colorectal cancer.
AB  - NTRK3 is a member of the neurotrophin receptor family and regulates cell
      survival. It appears to be a dependence receptor, and thus has the potential to
      act as an oncogene or as a tumor suppressor gene. NTRK3 is a receptor for NT-3
      and when bound to NT-3 it induces cell survival, but when NT-3 free, it induces
      apoptosis. We identified aberrantly methylated NTRK3 in colorectal cancers
      through a genome-wide screen for hypermethylated genes. This discovery led us to
      assess whether NTRK3 could be a tumor suppressor gene in the colon. NTRK3 is
      methylated in 60% of colon adenomas and 67% of colon adenocarcinomas. NTRK3
      methylation suppresses NTRK3 expression. Reconstitution of NTRK3 induces
      apoptosis in colorectal cancers, if NT-3 is absent. Furthermore, the loss of
      NTRK3 expression associates with neoplastic transformation in vitro and in vivo.
      We also found that a naturally occurring mutant NTRK3 found in human colorectal
      cancer inhibits the tumor suppressor activity of NTRK3. In summary, our findings
      suggest NTRK3 is a conditional tumor suppressor gene that is commonly inactivated
      in colorectal cancer by both epigenetic and genetic mechanisms whose function in
      the pathogenesis of colorectal cancer depends on the expression status of its
      ligand, NT-3. 

PMID- 23874206
TI  - EphrinA2 regulates clathrin mediated KSHV endocytosis in fibroblast cells by
      coordinating integrin-associated signaling and c-Cbl directed polyubiquitination.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with human dermal
      endothelial cell surface tyrosine kinase EphrinA2 (EphA2) and integrins
      (alpha3beta1 and alphaVbeta3) in the lipid raft (LR) region, and EphA2 regulates
      macropinocytic virus entry by coordinating integrin-c-Cbl associated signaling.
      In contrast, KSHV enters human foreskin fibroblast (HFF) cells by LR-independent
      clathrin mediated endocytosis. The present studies conducted to identify the key
      molecules regulating KSHV entry in HFF cells showed that KSHV induces association
      with integrins (alphaVbeta5, alphaVbeta3 and alpha3beta1) and EphA2 in non-LR
      regions early during infection and activates EphA2, which in turn associates with
      phosphorylated c-Cbl, myosin IIA, FAK, Src, and PI3-K, as well as clathrin and
      its adaptor AP2 and effector Epsin-15 proteins. EphA2 knockdown significantly
      reduced these signal inductions, virus internalization and gene expression. c-Cbl
      knockdown ablated the c-Cbl mediated K63 type polyubiquitination of EphA2 and
      clathrin association with EphA2 and KSHV. Mutations in EphA2's tyrosine kinase
      domain (TKD) or sterile alpha motif (SAM) abolished its interaction with c-Cbl.
      Mutations in tyrosine kinase binding (TKB) or RING finger (RF) domains of c-Cbl
      resulted in very poor association of c-Cbl with EphA2 and decreased EphA2
      polyubiquitination. These studies demonstrated the contributions of these domains
      in EphA2 and c-Cbl association, EphA2 polyubiquitination and virus-EphA2
      internalization. Collectively, these results revealed for the first time that
      EphA2 influences the tyrosine phosphorylation of clathrin, the role of EphA2 in
      clathrin mediated endocytosis of a virus, and c-Cbl mediated EphA2
      polyubiquitination directing KSHV entry in HFF cells via coordinated signal
      induction and progression of endocytic events, all of which suggest that
      targeting EphA2 and c-Cbl could block KSHV entry and infection. 

PMID- 23874208
TI  - Trans-ancestral studies fine map the SLE-susceptibility locus TNFSF4.
AB  - We previously established an 80 kb haplotype upstream of TNFSF4 as a
      susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at
      this locus are associated with inflammatory disorders, including atherosclerosis
      and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained
      elusive due to strong linkage disequilibrium exhibited by alleles spanning the
      region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900
      SLE and control subjects including Amerindian/Hispanics (1348 cases, 717
      controls), African-Americans (AA) (1529, 2048) and better powered cohorts of
      Europeans and East Asians, we find strong association of risk alleles in all
      ethnicities; the AA association replicates in African-American Gullah (152,122).
      The best evidence of association comes from two adjacent markers: rs2205960-T
      (P=1.71 * 10(-34) , OR=1.43[1.26-1.60]) and rs1234317-T (P=1.16 * 10(-28) ,
      OR=1.38[1.24-1.54]). Inference of fine-scale recombination rates for all
      populations tested finds the 80 kb risk and non-risk haplotypes in all except
      African-Americans. In this population the decay of recombination equates to an 11
      kb risk haplotype, anchored in the 5' region proximal to TNFSF4 and tagged by
      rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression
      analyses delineate the 5' risk signal to rs2205960-T and the independent non-risk
      signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust
      association of rs2205960-T with autoantibody production. The rs2205960-T is
      predicted to form part of a decameric motif which binds NF-kappaBp65 with
      increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-kappaB
      interaction with the DNA sequence at this position in LCL cells. Our research
      suggests association of rs2205960-T with SLE across multiple groups and an
      independent non-risk signal at rs1234314-C. rs2205960-T is associated with
      autoantibody production and lymphopenia. Our data confirm a global signal at
      TNFSF4 and a role for the expressed product at multiple stages of lymphocyte
      dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral
      mapping in a complex trait.

PMID- 23874209
TI  - Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1
      during Caenorhabditis elegans meiosis.
AB  - The generation and resolution of joint molecule recombination intermediates is
      required to ensure bipolar chromosome segregation during meiosis. During wild
      type meiosis in Caenorhabditis elegans, SPO-11-generated double stranded breaks
      are resolved to generate a single crossover per bivalent and the remaining
      recombination intermediates are resolved as noncrossovers. We discovered that
      early recombination intermediates are limited by the C. elegans BLM ortholog, HIM
      6, and in the absence of HIM-6 by the structure specific endonuclease MUS-81. In
      the absence of both MUS-81 and HIM-6, recombination intermediates persist,
      leading to chromosome breakage at diakinesis and inviable embryos. MUS-81 has an
      additional role in resolving late recombination intermediates in C. elegans. mus
      81 mutants exhibited reduced crossover recombination frequencies suggesting that
      MUS-81 is required to generate a subset of meiotic crossovers. Similarly, the
      Mus81-related endonuclease XPF-1 is also required for a subset of meiotic
      crossovers. Although C. elegans gen-1 mutants have no detectable meiotic defect
      either alone or in combination with him-6, mus-81 or xpf-1 mutations, mus-81;xpf
      1 double mutants are synthetic lethal. While mus-81;xpf-1 double mutants are
      proficient for the processing of early recombination intermediates, they exhibit
      defects in the post-pachytene chromosome reorganization and the asymmetric
      disassembly of the synaptonemal complex, presumably triggered by crossovers or
      crossover precursors. Consistent with a defect in resolving late recombination
      intermediates, mus-81; xpf-1 diakinetic bivalents are aberrant with fine DNA
      bridges visible between two distinct DAPI staining bodies. We were able to
      suppress the aberrant bivalent phenotype by microinjection of activated human
      GEN1 protein, which can cleave Holliday junctions, suggesting that the DNA
      bridges in mus-81; xpf-1 diakinetic oocytes are unresolved Holliday junctions. We
      propose that the MUS-81 and XPF-1 endonucleases act redundantly to process late
      recombination intermediates to form crossovers during C. elegans meiosis. 

PMID- 23874210
TI  - Interplay between structure-specific endonucleases for crossover control during
      Caenorhabditis elegans meiosis.
AB  - The number and distribution of crossover events are tightly regulated at prophase
      of meiosis I. The resolution of Holliday junctions by structure-specific
      endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main
      mechanisms proposed for crossover formation. However, how these nucleases
      coordinately resolve Holliday junctions is still unclear. Here we identify both
      the functional overlap and differences between these four nucleases regarding
      their roles in crossover formation and control in the Caenorhabditis elegans
      germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM
      18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects
      revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles
      with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles
      in processing recombination intermediates. Taking advantage of the ease of
      genetic analysis and high-resolution imaging afforded by C. elegans, we examined
      crossover designation, frequency, distribution and chromosomal morphology in
      single, double, triple and quadruple mutants of the structure-specific
      endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX
      1 in executing crossover formation during meiotic double-strand break repair.
      Analysis of crossover distribution revealed that SLX-1 is required for crossover
      suppression at the center region of the autosomes. Finally, analysis of
      chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1
      and XPF-1 promote meiotic chromosomal stability by preventing formation of
      chromosomal abnormalities. We propose a model in which coordinate action between
      structure-specific nucleases at different chromosome domains, namely MUS-81, SLX
      1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and
      negative regulatory roles, respectively, for crossover control during C. elegans
      meiosis. 

PMID- 23874211
TI  - Odoriferous Defensive stink gland transcriptome to identify novel genes necessary
      for quinone synthesis in the red flour beetle, Tribolium castaneum.
AB  - Chemical defense is one of the most important traits, which endow insects the
      ability to conquer a most diverse set of ecological environments. Chemical
      secretions are used for defense against anything from vertebrate or invertebrate
      predators to prokaryotic or eukaryotic parasites or food competitors. Tenebrionid
      beetles are especially prolific in this category, producing several varieties of
      substituted benzoquinone compounds. In order to get a better understanding of the
      genetic and molecular basis of defensive secretions, we performed RNA sequencing
      in a newly emerging insect model, the red flour beetle Tribolium castaneum
      (Coleoptera: Tenebrionidae). To detect genes that are highly and specifically
      expressed in the odoriferous gland tissues that secret defensive chemical
      compounds, we compared them to a control tissue, the anterior abdomen. 511 genes
      were identified in different subtraction groups. Of these, 77 genes were
      functionally analyzed by RNA interference (RNAi) to recognize induced gland
      alterations morphologically or changes in gland volatiles by gas chromatography
      mass spectrometry. 29 genes (38%) presented strong visible phenotypes, while 67
      genes (87%) showed alterations of at least one gland content. Three of these
      genes showing quinone-less (ql) phenotypes - Tcas-ql VTGl; Tcas-ql ARSB; Tcas-ql
      MRP - were isolated, molecularly characterized, their expression identified in
      both types of the secretory glandular cells, and their function determined by
      quantification of all main components after RNAi. In addition, microbe inhibition
      assays revealed that a quinone-free status is unable to impede bacterial or
      fungal growth. Phylogenetic analyses of these three genes indicate that they have
      evolved independently and specifically for chemical defense in beetles. 

PMID- 23874212
TI  - The RNA-binding proteins FMR1, rasputin and caprin act together with the UBA
      protein lingerer to restrict tissue growth in Drosophila melanogaster.
AB  - Appropriate expression of growth-regulatory genes is essential to ensure normal
      animal development and to prevent diseases like cancer. Gene regulation at the
      levels of transcription and translational initiation mediated by the Hippo and
      Insulin signaling pathways and by the TORC1 complex, respectively, has been well
      documented. Whether translational control mediated by RNA-binding proteins
      contributes to the regulation of cellular growth is less clear. Here, we identify
      Lingerer (Lig), an UBA domain-containing protein, as growth suppressor that
      associates with the RNA-binding proteins Fragile X mental retardation protein 1
      (FMR1) and Caprin (Capr) and directly interacts with and regulates the RNA
      binding protein Rasputin (Rin) in Drosophila melanogaster. lig mutant organs
      overgrow due to increased proliferation, and a reporter for the JAK/STAT
      signaling pathway is upregulated in a lig mutant situation. rin, Capr or FMR1 in
      combination as double mutants, but not the respective single mutants, display lig
      like phenotypes, implicating a redundant function of Rin, Capr and FMR1 in growth
      control in epithelial tissues. Thus, Lig regulates cell proliferation during
      development in concert with Rin, Capr and FMR1. 

PMID- 23874213
TI  - Role of CTCF protein in regulating FMR1 locus transcription.
AB  - Fragile X syndrome (FXS), the leading cause of inherited intellectual disability,
      is caused by epigenetic silencing of the FMR1 gene, through expansion and
      methylation of a CGG triplet repeat (methylated full mutation). An antisense
      transcript (FMR1-AS1), starting from both promoter and intron 2 of the FMR1 gene,
      was demonstrated in transcriptionally active alleles, but not in silent FXS
      alleles. Moreover, a DNA methylation boundary, which is lost in FXS, was recently
      identified upstream of the FMR1 gene. Several nuclear proteins bind to this
      region, like the insulator protein CTCF. Here we demonstrate for the first time
      that rare unmethylated full mutation (UFM) alleles present the same boundary
      described in wild type (WT) alleles and that CTCF binds to this region, as well
      as to the FMR1 gene promoter, exon 1 and intron 2 binding sites. Contrariwise,
      DNA methylation prevents CTCF binding to FXS alleles. Drug-induced CpGs
      demethylation does not restore this binding. CTCF knock-down experiments clearly
      established that CTCF does not act as insulator at the active FMR1 locus, despite
      the presence of a CGG expansion. CTCF depletion induces heterochromatinic histone
      configuration of the FMR1 locus and results in reduction of FMR1 transcription,
      which however is not accompanied by spreading of DNA methylation towards the FMR1
      promoter. CTCF depletion is also associated with FMR1-AS1 mRNA reduction.
      Antisense RNA, like sense transcript, is upregulated in UFM and absent in FXS
      cells and its splicing is correlated to that of the FMR1-mRNA. We conclude that
      CTCF has a complex role in regulating FMR1 expression, probably through the
      organization of chromatin loops between sense/antisense transcriptional
      regulatory regions, as suggested by bioinformatics analysis. 

PMID- 23874214
TI  - Prediction of complex human traits using the genomic best linear unbiased
      predictor.
AB  - Despite important advances from Genome Wide Association Studies (GWAS), for most
      complex human traits and diseases, a sizable proportion of genetic variance
      remains unexplained and prediction accuracy (PA) is usually low. Evidence
      suggests that PA can be improved using Whole-Genome Regression (WGR) models where
      phenotypes are regressed on hundreds of thousands of variants simultaneously. The
      Genomic Best Linear Unbiased Prediction (G-BLUP, a ridge-regression type method)
      is a commonly used WGR method and has shown good predictive performance when
      applied to plant and animal breeding populations. However, breeding and human
      populations differ greatly in a number of factors that can affect the predictive
      performance of G-BLUP. Using theory, simulations, and real data analysis, we
      study the performance of G-BLUP when applied to data from related and unrelated
      human subjects. Under perfect linkage disequilibrium (LD) between markers and
      QTL, the prediction R-squared (R(2)) of G-BLUP reaches trait-heritability,
      asymptotically. However, under imperfect LD between markers and QTL, prediction
      R(2) based on G-BLUP has a much lower upper bound. We show that the minimum
      decrease in prediction accuracy caused by imperfect LD between markers and QTL is
      given by (1-b)(2), where b is the regression of marker-derived genomic
      relationships on those realized at causal loci. For pairs of related individuals,
      due to within-family disequilibrium, the patterns of realized genomic similarity
      are similar across the genome; therefore b is close to one inducing small
      decrease in R(2). However, with distantly related individuals b reaches very low
      values imposing a very low upper bound on prediction R(2). Our simulations
      suggest that for the analysis of data from unrelated individuals, the asymptotic
      upper bound on R(2) may be of the order of 20% of the trait heritability. We show
      how PA can be enhanced with use of variable selection or differential shrinkage
      of estimates of marker effects. 

PMID- 23874215
TI  - ENU-induced mutation in the DNA-binding domain of KLF3 reveals important roles
      for KLF3 in cardiovascular development and function in mice.
AB  - KLF3 is a Kruppel family zinc finger transcription factor with widespread tissue
      expression and no previously known role in heart development. In a screen for
      dominant mutations affecting cardiovascular function in N-ethyl-N-nitrosourea
      (ENU) mutagenized mice, we identified a missense mutation in the Klf3 gene that
      caused aortic valvular stenosis and partially penetrant perinatal lethality in
      heterozygotes. All homozygotes died as embryos. In the first of three zinc
      fingers, a point mutation changed a highly conserved histidine at amino acid 275
      to arginine (Klf3(H275R) ). This change impaired binding of the mutant protein to
      KLF3's canonical DNA binding sequence. Heterozygous Klf3(H275R) mutants that died
      as neonates had marked biventricular cardiac hypertrophy with diminished cardiac
      chambers. Adult survivors exhibited hypotension, cardiac hypertrophy with
      enlarged cardiac chambers, and aortic valvular stenosis. A dominant negative
      effect on protein function was inferred by the similarity in phenotype between
      heterozygous Klf3(H275R) mutants and homozygous Klf3 null mice. However, the
      existence of divergent traits suggested the involvement of additional
      interactions. We conclude that KLF3 plays diverse and important roles in
      cardiovascular development and function in mice, and that amino acid 275 is
      critical for normal KLF3 protein function. Future exploration of the KLF3 pathway
      provides a new avenue for investigating causative factors contributing to
      cardiovascular disorders in humans. 

PMID- 23874216
TI  - The conserved intronic cleavage and polyadenylation site of CstF-77 gene imparts
      control of 3' end processing activity through feedback autoregulation and by U1
      snRNP.
AB  - The human gene encoding the cleavage/polyadenylation (C/P) factor CstF-77
      contains 21 exons. However, intron 3 (In3) accounts for nearly half of the gene
      region, and contains a C/P site (pA) with medium strength, leading to short mRNA
      isoforms with no apparent protein products. This intron contains a weak 5' splice
      site (5'SS), opposite to the general trend for large introns in the human genome.
      Importantly, the intron size and strengths of 5'SS and pA are all highly
      conserved across vertebrates, and perturbation of these parameters drastically
      alters intronic C/P. We found that the usage of In3 pA is responsive to the
      expression level of CstF-77 as well as several other C/P factors, indicating it
      attenuates the expression of CstF-77 via a negative feedback mechanism.
      Significantly, intronic C/P of CstF-77 pre-mRNA correlates with global 3'UTR
      length across cells and tissues. In addition, inhibition of U1 snRNP also leads
      to regulation of the usage of In3 pA, suggesting that the C/P activity in the
      cell can be cross-regulated by splicing, leading to coordination between these
      two processes. Importantly, perturbation of CstF-77 expression leads to
      widespread alternative cleavage and polyadenylation (APA) and disturbance of cell
      proliferation and differentiation. Thus, the conserved intronic pA of the CstF-77
      gene may function as a sensor for cellular C/P and splicing activities,
      controlling the homeostasis of CstF-77 and C/P activity and impacting cell
      proliferation and differentiation. 

PMID- 23874217
TI  - FGF signalling regulates chromatin organisation during neural differentiation via
      mechanisms that can be uncoupled from transcription.
AB  - Changes in higher order chromatin organisation have been linked to
      transcriptional regulation; however, little is known about how such organisation
      alters during embryonic development or how it is regulated by extrinsic signals.
      Here we analyse changes in chromatin organisation as neural differentiation
      progresses, exploiting the clear spatial separation of the temporal events of
      differentiation along the elongating body axis of the mouse embryo. Combining
      fluorescence in situ hybridisation with super-resolution structured illumination
      microscopy, we show that chromatin around key differentiation gene loci Pax6 and
      Irx3 undergoes both decompaction and displacement towards the nuclear centre
      coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as
      neural differentiation commences correlates with a more peripheral nuclear
      position of this locus. During normal neural differentiation, fibroblast growth
      factor (FGF) signalling is repressed by retinoic acid, and this vitamin A
      derivative is further required for transcription of neural genes. We show here
      that exposure to retinoic acid or inhibition of FGF signalling promotes
      precocious decompaction and central nuclear positioning of differentiation gene
      loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find
      that such changes in higher order chromatin organisation are dependent on
      retinoid signalling. In this retinoid deficient condition, FGF signalling
      persists ectopically in the elongating body, and importantly, we find that
      inhibiting FGF receptor (FGFR) signalling in Raldh2-/- embryos does not rescue
      differentiation gene transcription, but does elicit both chromatin decompaction
      and nuclear position change. These findings demonstrate that regulation of higher
      order chromatin organisation during differentiation in the embryo can be
      uncoupled from the machinery that promotes transcription and, for the first time,
      identify FGF as an extrinsic signal that can direct chromatin compaction and
      nuclear organisation of gene loci. 

PMID- 23874218
TI  - Exquisite light sensitivity of Drosophila melanogaster cryptochrome.
AB  - Drosophila melanogaster shows exquisite light sensitivity for modulation of
      circadian functions in vivo, yet the activities of the Drosophila circadian
      photopigment cryptochrome (CRY) have only been observed at high light levels. We
      studied intensity/duration parameters for light pulse induced circadian phase
      shifts under dim light conditions in vivo. Flies show far greater light
      sensitivity than previously appreciated, and show a surprising sensitivity
      increase with pulse duration, implying a process of photic integration active up
      to at least 6 hours. The CRY target timeless (TIM) shows dim light dependent
      degradation in circadian pacemaker neurons that parallels phase shift amplitude,
      indicating that integration occurs at this step, with the strongest effect in a
      single identified pacemaker neuron. Our findings indicate that CRY compensates
      for limited light sensitivity in vivo by photon integration over extraordinarily
      long times, and point to select circadian pacemaker neurons as having important
      roles. 

PMID- 23874219
TI  - The conserved ADAMTS-like protein lonely heart mediates matrix formation and
      cardiac tissue integrity.
AB  - Here we report on the identification and functional characterization of the
      ADAMTS-like homolog lonely heart (loh) in Drosophila melanogaster. Loh displays
      all hallmarks of ADAMTSL proteins including several thrombospondin type 1 repeats
      (TSR1), and acts in concert with the collagen Pericardin (Prc). Loss of either
      loh or prc causes progressive cardiac damage peaking in the abolishment of heart
      function. We show that both proteins are integral components of the cardiac ECM
      mediating cellular adhesion between the cardiac tube and the pericardial cells.
      Loss of ECM integrity leads to an altered myo-fibrillar organization in cardiac
      cells massively influencing heart beat pattern. We show evidence that Loh acts as
      a secreted receptor for Prc and works as a crucial determinant to allow the
      formation of a cell and tissue specific ECM, while it does not influence the
      accumulation of other matrix proteins like Nidogen or Perlecan. Our findings
      demonstrate that the function of ADAMTS-like proteins is conserved throughout
      evolution and reveal a previously unknown interaction of these proteins with
      collagens. 

PMID- 23874220
TI  - Bacterial adaptation through loss of function.
AB  - The metabolic capabilities and regulatory networks of bacteria have been
      optimized by evolution in response to selective pressures present in each
      species' native ecological niche. In a new environment, however, the same
      bacteria may grow poorly due to regulatory constraints or biochemical
      deficiencies. Adaptation to such conditions can proceed through the acquisition
      of new cellular functionality due to gain of function mutations or via modulation
      of cellular networks. Using selection experiments on transposon-mutagenized
      libraries of bacteria, we illustrate that even under conditions of extreme
      nutrient limitation, substantial adaptation can be achieved solely through loss
      of function mutations, which rewire the metabolism of the cell without gain of
      enzymatic or sensory function. A systematic analysis of similar experiments under
      more than 100 conditions reveals that adaptive loss of function mutations exist
      for many environmental challenges. Drawing on a wealth of examples from published
      articles, we detail the range of mechanisms through which loss-of-function
      mutations can generate such beneficial regulatory changes, without the need for
      rare, specific mutations to fine-tune enzymatic activities or network
      connections. The high rate at which loss-of-function mutations occur suggests
      that null mutations play an underappreciated role in the early stages of adaption
      of bacterial populations to new environments. 

PMID- 23874221
TI  - The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive
      behavioral sensitivity.
AB  - Signaling levels within sensory neurons must be tightly regulated to allow cells
      to integrate information from multiple signaling inputs and to respond to new
      stimuli. Herein we report a new role for the cGMP-dependent protein kinase EGL-4
      in the negative regulation of G protein-coupled nociceptive chemosensory
      signaling. C. elegans lacking EGL-4 function are hypersensitive in their
      behavioral response to low concentrations of the bitter tastant quinine and
      exhibit an elevated calcium flux in the ASH sensory neurons in response to
      quinine. We provide the first direct evidence for cGMP/PKG function in ASH and
      propose that ODR-1, GCY-27, GCY-33 and GCY-34 act in a non-cell-autonomous manner
      to provide cGMP for EGL-4 function in ASH. Our data suggest that activated EGL-4
      dampens quinine sensitivity via phosphorylation and activation of the regulator
      of G protein signaling (RGS) proteins RGS-2 and RGS-3, which in turn downregulate
      Galpha signaling and behavioral sensitivity. 

PMID- 23874222
TI  - Selective pressures to maintain attachment site specificity of integrative and
      conjugative elements.
AB  - Integrative and conjugative elements (ICEs) are widespread mobile genetic
      elements that are usually found integrated in bacterial chromosomes. They are
      important agents of evolution and contribute to the acquisition of new traits,
      including antibiotic resistances. ICEs can excise from the chromosome and
      transfer to recipients by conjugation. Many ICEs are site-specific in that they
      integrate preferentially into a primary attachment site in the bacterial genome.
      Site-specific ICEs can also integrate into secondary locations, particularly if
      the primary site is absent. However, little is known about the consequences of
      integration of ICEs into alternative attachment sites or what drives the apparent
      maintenance and prevalence of the many ICEs that use a single attachment site.
      Using ICEBs1, a site-specific ICE from Bacillus subtilis that integrates into a
      tRNA gene, we found that integration into secondary sites was detrimental to both
      ICEBs1 and the host cell. Excision of ICEBs1 from secondary sites was impaired
      either partially or completely, limiting the spread of ICEBs1. Furthermore,
      induction of ICEBs1 gene expression caused a substantial drop in proliferation
      and cell viability within three hours. This drop was dependent on rolling circle
      replication of ICEBs1 that was unable to excise from the chromosome. Together,
      these detrimental effects provide selective pressure against the survival and
      dissemination of ICEs that have integrated into alternative sites and may explain
      the maintenance of site-specific integration for many ICEs. 

PMID- 23874223
TI  - Gene set signature of reversal reaction type I in leprosy patients.
AB  - Leprosy reversal reactions type 1 (T1R) are acute immune episodes that affect a
      subset of leprosy patients and remain a major cause of nerve damage. Little is
      known about the relative importance of innate versus environmental factors in the
      pathogenesis of T1R. In a retrospective design, we evaluated innate differences
      in response to Mycobacterium leprae between healthy individuals and former
      leprosy patients affected or free of T1R by analyzing the transcriptome response
      of whole blood to M. leprae sonicate. Validation of results was conducted in a
      subsequent prospective study. We observed the differential expression of 581
      genes upon exposure of whole blood to M. leprae sonicate in the retrospective
      study. We defined a 44 T1R gene set signature of differentially regulated genes.
      The majority of the T1R set genes were represented by three functional groups: i)
      pro-inflammatory regulators; ii) arachidonic acid metabolism mediators; and iii)
      regulators of anti-inflammation. The validity of the T1R gene set signature was
      replicated in the prospective arm of the study. The T1R genetic signature
      encompasses genes encoding pro- and anti-inflammatory mediators of innate
      immunity. This suggests an innate defect in the regulation of the inflammatory
      response to M. leprae antigens. The identified T1R gene set represents a critical
      first step towards a genetic profile of leprosy patients who are at increased
      risk of T1R and concomitant nerve damage. 

PMID- 23874224
TI  - The arabidopsis RNA binding protein with K homology motifs, SHINY1, interacts
      with the C-terminal domain phosphatase-like 1 (CPL1) to repress stress-inducible
      gene expression.
AB  - The phosphorylation state of the C-terminal domain (CTD) of the RNA polymerase II
      plays crucial roles in transcription and mRNA processing. Previous studies showed
      that the plant CTD phosphatase-like 1 (CPL1) dephosphorylates Ser-5-specific CTD
      and regulates abiotic stress response in Arabidopsis. Here, we report the
      identification of a K-homology domain-containing protein named SHINY1 (SHI1) that
      interacts with CPL1 to modulate gene expression. The shi1 mutant was isolated
      from a forward genetic screening for mutants showing elevated expression of the
      luciferase reporter gene driven by a salt-inducible promoter. The shi1 mutant is
      more sensitive to cold treatment during vegetative growth and insensitive to
      abscisic acid in seed germination, resembling the phenotypes of shi4 that is
      allelic to the cpl1 mutant. Both SHI1 and SHI4/CPL1 are nuclear-localized
      proteins. SHI1 interacts with SHI4/CPL1 in vitro and in vivo. Loss-of-function
      mutations in shi1 and shi4 resulted in similar changes in the expression of some
      stress-inducible genes. Moreover, both shi1 and shi4 mutants display higher mRNA
      capping efficiency and altered polyadenylation site selection for some of the
      stress-inducible genes, when compared with wild type. We propose that the SHI1
      SHI4/CPL1 complex inhibits transcription by preventing mRNA capping and
      transition from transcription initiation to elongation. 

PMID- 23874225
TI  - miR-133a regulates adipocyte browning in vivo.
AB  - Prdm16 determines the bidirectional fate switch of skeletal muscle/brown adipose
      tissue (BAT) and regulates the thermogenic gene program of subcutaneous white
      adipose tissue (SAT) in mice. Here we show that miR-133a, a microRNA that is
      expressed in both BAT and SATs, directly targets the 3' UTR of Prdm16. The
      expression of miR-133a dramatically decreases along the commitment and
      differentiation of brown preadipocytes, accompanied by the upregulation of
      Prdm16. Overexpression of miR-133a in BAT and SAT cells significantly inhibits,
      and conversely inhibition of miR-133a upregulates, Prdm16 and brown adipogenesis.
      More importantly, double knockout of miR-133a1 and miR-133a2 in mice leads to
      elevations of the brown and thermogenic gene programs in SAT. Even 75% deletion
      of miR-133a (a1(-/-)a2(+/-) ) genes results in browning of SAT, manifested by the
      appearance of numerous multilocular UCP1-expressing adipocytes within SAT.
      Additionally, compared to wildtype mice, miR-133a1(-/-)a2(+/-) mice exhibit
      increased insulin sensitivity and glucose tolerance, and activate the thermogenic
      gene program more robustly upon cold exposure. These results together elucidate a
      crucial role of miR-133a in the regulation of adipocyte browning in vivo. 

PMID- 23874226
TI  - The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in
      Drosophila melanogaster through maintaining a progenitor-like cell state.
AB  - The capacity of tumour cells to maintain continual overgrowth potential has been
      linked to the commandeering of normal self-renewal pathways. Using an epithelial
      cancer model in Drosophila melanogaster, we carried out an overexpression screen
      for oncogenes capable of cooperating with the loss of the epithelial apico-basal
      cell polarity regulator, scribbled (scrib), and identified the cell fate
      regulator, Abrupt, a BTB-zinc finger protein. Abrupt overexpression alone is
      insufficient to transform cells, but in cooperation with scrib loss of function,
      Abrupt promotes the formation of massive tumours in the eye/antennal disc. The
      steroid hormone receptor coactivator, Taiman (a homologue of SRC3/AIB1), is known
      to associate with Abrupt, and Taiman overexpression also drives tumour formation
      in cooperation with the loss of Scrib. Expression arrays and ChIP-Seq indicates
      that Abrupt overexpression represses a large number of genes, including steroid
      hormone-response genes and multiple cell fate regulators, thereby maintaining
      cells within an epithelial progenitor-like state. The progenitor-like state is
      characterised by the failure to express the conserved Eyes absent/Dachshund
      regulatory complex in the eye disc, and in the antennal disc by the failure to
      express cell fate regulators that define the temporal elaboration of the
      appendage along the proximo-distal axis downstream of Distalless. Loss of scrib
      promotes cooperation with Abrupt through impaired Hippo signalling, which is
      required and sufficient for cooperative overgrowth with Abrupt, and JNK (Jun
      kinase) signalling, which is required for tumour cell migration/invasion but not
      overgrowth. These results thus identify a novel cooperating oncogene, identify
      mammalian family members of which are also known oncogenes, and demonstrate that
      epithelial tumours in Drosophila can be characterised by the maintenance of a
      progenitor-like state. 

PMID- 23874228
TI  - Fine time course expression analysis identifies cascades of activation and
      repression and maps a putative regulator of mammalian sex determination.
AB  - In vertebrates, primary sex determination refers to the decision within a
      bipotential organ precursor to differentiate as a testis or ovary. Bifurcation of
      organ fate begins between embryonic day (E) 11.0-E12.0 in mice and likely
      involves a dynamic transcription network that is poorly understood. To elucidate
      the first steps of sexual fate specification, we profiled the XX and XY gonad
      transcriptomes at fine granularity during this period and resolved cascades of
      gene activation and repression. C57BL/6J (B6) XY gonads showed a consistent ~5
      hour delay in the activation of most male pathway genes and repression of female
      pathway genes relative to 129S1/SvImJ, which likely explains the sensitivity of
      the B6 strain to male-to-female sex reversal. Using this fine time course data,
      we predicted novel regulatory genes underlying expression QTLs (eQTLs) mapped in
      a previous study. To test predictions, we developed an in vitro gonad primary
      cell assay and optimized a lentivirus-based shRNA delivery method to silence
      candidate genes and quantify effects on putative targets. We provide strong
      evidence that Lmo4 (Lim-domain only 4) is a novel regulator of sex determination
      upstream of SF1 (Nr5a1), Sox9, Fgf9, and Col9a3. This approach can be readily
      applied to identify regulatory interactions in other systems.

PMID- 23874227
TI  - Gata4 is required for formation of the genital ridge in mice.
AB  - In mammals, both testis and ovary arise from a sexually undifferentiated
      precursor, the genital ridge, which first appears during mid-gestation as a
      thickening of the coelomic epithelium on the ventromedial surface of the
      mesonephros. At least four genes (Lhx9, Sf1, Wt1, and Emx2) have been
      demonstrated to be required for subsequent growth and maintenance of the genital
      ridge. However, no gene has been shown to be required for the initial thickening
      of the coelomic epithelium during genital ridge formation. We report that the
      transcription factor GATA4 is expressed in the coelomic epithelium of the genital
      ridge, progressing in an anterior-to-posterior (A-P) direction, immediately
      preceding an A-P wave of epithelial thickening. Mouse embryos conditionally
      deficient in Gata4 show no signs of gonadal initiation, as their coelomic
      epithelium remains a morphologically undifferentiated monolayer. The failure of
      genital ridge formation in Gata4-deficient embryos is corroborated by the absence
      of the early gonadal markers LHX9 and SF1. Our data indicate that GATA4 is
      required to initiate formation of the genital ridge in both XX and XY fetuses,
      prior to its previously reported role in testicular differentiation of the XY
      gonad. 

PMID- 23874229
TI  - Genome-scale co-evolutionary inference identifies functions and clients of
      bacterial Hsp90.
AB  - The molecular chaperone Hsp90 is essential in eukaryotes, in which it facilitates
      the folding of developmental regulators and signal transduction proteins known as
      Hsp90 clients. In contrast, Hsp90 is not essential in bacteria, and a broad
      characterization of its molecular and organismal function is lacking. To enable
      such characterization, we used a genome-scale phylogenetic analysis to identify
      genes that co-evolve with bacterial Hsp90. We find that genes whose gain and loss
      were coordinated with Hsp90 throughout bacterial evolution tended to function in
      flagellar assembly, chemotaxis, and bacterial secretion, suggesting that Hsp90
      may aid assembly of protein complexes. To add to the limited set of known
      bacterial Hsp90 clients, we further developed a statistical method to predict
      putative clients. We validated our predictions by demonstrating that the
      flagellar protein FliN and the chemotaxis kinase CheA behaved as Hsp90 clients in
      Escherichia coli, confirming the predicted role of Hsp90 in chemotaxis and
      flagellar assembly. Furthermore, normal Hsp90 function is important for wild-type
      motility and/or chemotaxis in E. coli. This novel function of bacterial Hsp90
      agreed with our subsequent finding that Hsp90 is associated with a preference for
      multiple habitats and may therefore face a complex selection regime. Taken
      together, our results reveal previously unknown functions of bacterial Hsp90 and
      open avenues for future experimental exploration by implicating Hsp90 in the
      assembly of membrane protein complexes and adaptation to novel environments. 

PMID- 23874230
TI  - Genomic analysis of natural selection and phenotypic variation in high-altitude
      mongolians.
AB  - Deedu (DU) Mongolians, who migrated from the Mongolian steppes to the Qinghai
      Tibetan Plateau approximately 500 years ago, are challenged by environmental
      conditions similar to native Tibetan highlanders. Identification of adaptive
      genetic factors in this population could provide insight into coordinated
      physiological responses to this environment. Here we examine genomic and
      phenotypic variation in this unique population and present the first complete
      analysis of a Mongolian whole-genome sequence. High-density SNP array data
      demonstrate that DU Mongolians share genetic ancestry with other Mongolian as
      well as Tibetan populations, specifically in genomic regions related with
      adaptation to high altitude. Several selection candidate genes identified in DU
      Mongolians are shared with other Asian groups (e.g., EDAR), neighboring Tibetan
      populations (including high-altitude candidates EPAS1, PKLR, and CYP2E1), as well
      as genes previously hypothesized to be associated with metabolic adaptation
      (e.g., PPARG). Hemoglobin concentration, a trait associated with high-altitude
      adaptation in Tibetans, is at an intermediate level in DU Mongolians compared to
      Tibetans and Han Chinese at comparable altitude. Whole-genome sequence from a DU
      Mongolian (Tianjiao1) shows that about 2% of the genomic variants, including more
      than 300 protein-coding changes, are specific to this individual. Our analyses of
      DU Mongolians and the first Mongolian genome provide valuable insight into
      genetic adaptation to extreme environments. 

PMID- 23874231
TI  - Independent evolution of transcriptional inactivation on sex chromosomes in birds
      and mammals.
AB  - X chromosome inactivation in eutherian mammals has been thought to be tightly
      controlled, as expected from a mechanism that compensates for the different
      dosage of X-borne genes in XX females and XY males. However, many X genes escape
      inactivation in humans, inactivation of the X in marsupials is partial, and the
      unrelated sex chromosomes of monotreme mammals have incomplete and gene-specific
      inactivation of X-linked genes. The bird ZW sex chromosome system represents a
      third independently evolved amniote sex chromosome system with dosage
      compensation, albeit partial and gene-specific, via an unknown mechanism (i.e.
      upregulation of the single Z in females, down regulation of one or both Zs in
      males, or a combination). We used RNA-fluorescent in situ hybridization (RNA
      FISH) to demonstrate, on individual fibroblast cells, inactivation of 11 genes on
      the chicken Z and 28 genes on the X chromosomes of platypus. Each gene displayed
      a reproducible frequency of 1Z/1X-active and 2Z/2X-active cells in the
      homogametic sex. Our results indicate that the probability of inactivation is
      controlled on a gene-by-gene basis (or small domains) on the chicken Z and
      platypus X chromosomes. This regulatory mechanism must have been exapted
      independently to the non-homologous sex chromosomes in birds and mammals in
      response to an over-expressed Z or X in the homogametic sex, highlighting the
      universal importance that (at least partial) silencing plays in the evolution on
      amniote dosage compensation and, therefore, the differentiation of sex
      chromosomes. 

PMID- 23874233
TI  - Defective repair of oxidative base lesions by the DNA glycosylase Nth1 associates
      with multiple telomere defects.
AB  - Telomeres are chromosome end structures and are essential for maintenance of
      genome stability. Highly repetitive telomere sequences appear to be susceptible
      to oxidative stress-induced damage. Oxidation may therefore have a severe impact
      on telomere integrity and function. A wide spectrum of oxidative pyrimidine
      derivatives has been reported, including thymine glycol (Tg), that are primarily
      removed by a DNA glycosylase, Endonuclease III-like protein 1 (Nth1). Here, we
      investigate the effect of Nth1 deficiency on telomere integrity in mice. Nth1
      null (Nth1(-/-) ) mouse tissues and primary MEFs harbor higher levels of
      Endonuclease III-sensitive DNA lesions at telomeric repeats, in comparison to a
      non-telomeric locus. Furthermore, oxidative DNA damage induced by acute exposure
      to an oxidant is repaired slowly at telomeres in Nth1(-/-) MEFs. Although
      telomere length is not affected in the hematopoietic tissues of Nth1(-/-) adult
      mice, telomeres suffer from attrition and increased recombination and DNA damage
      foci formation in Nth1(-/-) bone marrow cells that are stimulated ex vivo in the
      presence of 20% oxygen. Nth1 deficiency also enhances telomere fragility in mice.
      Lastly, in a telomerase null background, Nth1(-/-) bone marrow cells undergo
      severe telomere loss at some chromosome ends and cell apoptosis upon replicative
      stress. These results suggest that Nth1 plays an important role in telomere
      maintenance and base repair against oxidative stress-induced base modifications.
      The fact that telomerase deficiency can exacerbate telomere shortening in Nth1
      deficient mouse cells supports that base excision repair cooperates with
      telomerase to maintain telomere integrity. 

PMID- 23874232
TI  - The cohesion protein SOLO associates with SMC1 and is required for synapsis,
      recombination, homolog bias and cohesion and pairing of centromeres in Drosophila
      Meiosis.
AB  - Cohesion between sister chromatids is mediated by cohesin and is essential for
      proper meiotic segregation of both sister chromatids and homologs. solo encodes a
      Drosophila meiosis-specific cohesion protein with no apparent sequence homology
      to cohesins that is required in male meiosis for centromere cohesion, proper
      orientation of sister centromeres and centromere enrichment of the cohesin
      subunit SMC1. In this study, we show that solo is involved in multiple aspects of
      meiosis in female Drosophila. Null mutations in solo caused the following
      phenotypes: 1) high frequencies of homolog and sister chromatid nondisjunction
      (NDJ) and sharply reduced frequencies of homolog exchange; 2) reduced
      transmission of a ring-X chromosome, an indicator of elevated frequencies of
      sister chromatid exchange (SCE); 3) premature loss of centromere pairing and
      cohesion during prophase I, as indicated by elevated foci counts of the
      centromere protein CID; 4) instability of the lateral elements (LE)s and central
      regions of synaptonemal complexes (SCs), as indicated by fragmented and spotty
      staining of the chromosome core/LE component SMC1 and the transverse filament
      protein C(3)G, respectively, at all stages of pachytene. SOLO and SMC1 are both
      enriched on centromeres throughout prophase I, co-align along the lateral
      elements of SCs and reciprocally co-immunoprecipitate from ovarian protein
      extracts. Our studies demonstrate that SOLO is closely associated with meiotic
      cohesin and required both for enrichment of cohesin on centromeres and stable
      assembly of cohesin into chromosome cores. These events underlie and are required
      for stable cohesion of centromeres, synapsis of homologous chromosomes, and a
      recombination mechanism that suppresses SCE to preferentially generate homolog
      crossovers (homolog bias). We propose that SOLO is a subunit of a specialized
      meiotic cohesin complex that mediates both centromeric and axial arm cohesion and
      promotes homolog bias as a component of chromosome cores. 

PMID- 23874234
TI  - SLC26A4 targeted to the endolymphatic sac rescues hearing and balance in Slc26a4
      mutant mice.
AB  - Mutations of SLC26A4 are a common cause of human hearing loss associated with
      enlargement of the vestibular aqueduct. SLC26A4 encodes pendrin, an anion
      exchanger expressed in a variety of epithelial cells in the cochlea, the
      vestibular labyrinth and the endolymphatic sac. Slc26a4 (Delta/Delta) mice are
      devoid of pendrin and develop a severe enlargement of the membranous labyrinth,
      fail to acquire hearing and balance, and thereby provide a model for the human
      phenotype. Here, we generated a transgenic mouse line that expresses human
      SLC26A4 controlled by the promoter of ATP6V1B1. Crossing this transgene into the
      Slc26a4 (Delta/Delta) line restored protein expression of pendrin in the
      endolymphatic sac without inducing detectable expression in the cochlea or the
      vestibular sensory organs. The transgene prevented abnormal enlargement of the
      membranous labyrinth, restored a normal endocochlear potential, normal pH
      gradients between endolymph and perilymph in the cochlea, normal otoconia
      formation in the vestibular labyrinth and normal sensory functions of hearing and
      balance. Our study demonstrates that restoration of pendrin to the endolymphatic
      sac is sufficient to restore normal inner ear function. This finding in
      conjunction with our previous report that pendrin expression is required for
      embryonic development but not for the maintenance of hearing opens the prospect
      that a spatially and temporally limited therapy will restore normal hearing in
      human patients carrying a variety of mutations of SLC26A4. 

PMID- 23874235
TI  - Stepwise activation of the ATR signaling pathway upon increasing replication
      stress impacts fragile site integrity.
AB  - Breaks at common fragile sites (CFS) are a recognized source of genome
      instability in pre-neoplastic lesions, but how such checkpoint-proficient cells
      escape surveillance and continue cycling is unknown. Here we show, in lymphocytes
      and fibroblasts, that moderate replication stresses like those inducing breaks at
      CFSs trigger chromatin loading of sensors and mediators of the ATR pathway but
      fail to activate Chk1 or p53. Consistently, we found that cells depleted of ATR,
      but not of Chk1, accumulate single-stranded DNA upon Mre11-dependent resection of
      collapsed forks. Partial activation of the pathway under moderate stress thus
      takes steps against fork disassembly but tolerates S-phase progression and
      mitotic onset. We show that fork protection by ATR is crucial to CFS integrity,
      specifically in the cell type where a given site displays paucity in backup
      replication origins. Tolerance to mitotic entry with under-replicated CFSs
      therefore results in chromosome breaks, providing a pool of cells committed to
      further instability. 

PMID- 23874236
TI  - Genome-wide association mapping in dogs enables identification of the homeobox
      gene, NKX2-8, as a genetic component of neural tube defects in humans.
AB  - Neural tube defects (NTDs) is a general term for central nervous system
      malformations secondary to a failure of closure or development of the neural
      tube. The resulting pathologies may involve the brain, spinal cord and/or
      vertebral column, in addition to associated structures such as soft tissue or
      skin. The condition is reported among the more common birth defects in humans,
      leading to significant infant morbidity and mortality. The etiology remains
      poorly understood but genetic, nutritional, environmental factors, or a
      combination of these, are known to play a role in the development of NTDs. The
      variable conditions associated with NTDs occur naturally in dogs, and have been
      previously reported in the Weimaraner breed. Taking advantage of the strong
      linkage-disequilibrium within dog breeds we performed genome-wide association
      analysis and mapped a genomic region for spinal dysraphism, a presumed NTD, using
      4 affected and 96 unaffected Weimaraners. The associated region on canine
      chromosome 8 (pgenome  =3.0 * 10(-5)), after 100,000 permutations, encodes 18
      genes, including NKX2-8, a homeobox gene which is expressed in the developing
      neural tube. Sequencing NKX2-8 in affected Weimaraners revealed a G to AA
      frameshift mutation within exon 2 of the gene, resulting in a premature stop
      codon that is predicted to produce a truncated protein. The exons of NKX2-8 were
      sequenced in human patients with spina bifida and rare variants (rs61755040 and
      rs10135525) were found to be significantly over-represented (p=0.036). This is
      the first documentation of a potential role for NKX2-8 in the etiology of NTDs,
      made possible by investigating the molecular basis of naturally occurring
      mutations in dogs.

PMID- 23874237
TI  - Modification of tRNA(Lys) UUU by elongator is essential for efficient translation
      of stress mRNAs.
AB  - The Elongator complex, including the histone acetyl transferase Sin3/Elp3, was
      isolated as an RNA polymerase II-interacting complex, and cells deficient in
      Elongator subunits display transcriptional defects. However, it has also been
      shown that Elongator mediates the modification of some tRNAs, modulating
      translation efficiency. We show here that the fission yeast Sin3/Elp3 is
      important for oxidative stress survival. The stress transcriptional program,
      governed by the Sty1-Atf1-Pcr1 pathway, is affected in mutant cells, but not
      severely. On the contrary, cells lacking Sin3/Elp3 cannot modify the uridine
      wobble nucleoside of certain tRNAs, and other tRNA modifying activities such as
      Ctu1-Ctu2 are also essential for normal tolerance to H2O2. In particular, a
      plasmid over-expressing the tRNA(Lys) UUU complements the stress-related
      phenotypes of Sin3/Elp3 mutant cells. We have determined that the main H2O2
      dependent genes, including those coding for the transcription factors Atf1 and
      Pcr1, are highly expressed mRNAs containing a biased number of lysine-coding
      codons AAA versus AAG. Thus, their mRNAs are poorly translated after stress in
      cells lacking Sin3/Elp3 or Ctu2, whereas a mutated atf1 transcript with AAA-to
      AAG lysine codons is efficiently translated in all strain backgrounds. Our study
      demonstrates that the lack of a functional Elongator complex results in stress
      phenotypes due to its contribution to tRNA modification and subsequent
      translation inefficiency of certain stress-induced, highly expressed mRNAs. These
      results suggest that the transcriptional defects of these strain backgrounds may
      be a secondary consequence of the deficient expression of a transcription factor,
      Atf1-Pcr1, and other components of the transcriptional machinery. 

PMID- 23874238
TI  - Disease-related growth factor and embryonic signaling pathways modulate an
      enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus.
AB  - Coronary heart disease (CHD) is the leading cause of mortality in both developed
      and developing countries worldwide. Genome-wide association studies (GWAS) have
      now identified 46 independent susceptibility loci for CHD, however, the
      biological and disease-relevant mechanisms for these associations remain elusive.
      The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD
      associated locus at chromosome 6q23.2, a region containing the transcription
      factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix
      loop-helix (bHLH) transcription factor family, and regulates cell fate decisions
      and differentiation in the developing coronary vasculature. Herein, we
      characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287
      disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by
      allele-specific transcriptional regulation, transcription factor binding, and
      chromatin organization, leading to altered TCF21 expression. Further, this
      element is shown to mediate signaling through platelet-derived growth factor
      receptor beta (PDGFR-beta) and Wilms tumor 1 (WT1) pathways. A second disease
      allele identified in East Asians also appears to disrupt an AP-1-like element.
      Thus, both disease-related growth factor and embryonic signaling pathways may
      regulate CHD risk through two independent alleles at TCF21. 

PMID- 23874239
TI  - Strabismus promotes recruitment and degradation of farnesylated prickle in
      Drosophila melanogaster planar polarity specification.
AB  - The core planar polarity proteins are required to specify the orientation of
      structures that are polarised in the plane of the epithelium. In the Drosophila
      melanogaster wing, the core proteins localise asymmetrically at either proximal
      or distal cell edges. Asymmetric localisation is thought to be biased by long
      range cues, causing asymmetric complexes to become aligned with the tissue axes.
      Core proteins are then thought to participate in feedback interactions that are
      necessary to amplify asymmetry, and in order for such feedback interactions to
      operate correctly, the levels of the core proteins at junctions must be tightly
      regulated. We have investigated regulation of the core protein Prickle (Pk) in
      the pupal wing. The core protein Strabismus (Stbm) is required to recruit Pk into
      asymmetric complexes at proximal cell ends, and we report here that it also
      promotes proteasomal degradation of excess Pk, probably via a Cullin-1 dependent
      process. We also show for the first time that Pk is farnesylated in vivo, and
      this is essential for Pk function in the wing. Notably, farnesylation of Pk is
      necessary for it to be recruited into asymmetric complexes and function in
      feedback amplification, probably by reinforcing weak direct interactions between
      Stbm and Pk. Furthermore, farnesylation is also required for Stbm to promote
      proteasomal degradation of Pk. We propose that Stbm recruits farnesylated Pk into
      asymmetric complexes, but also promotes degradation of excess Pk that would
      otherwise perturb feedback amplification. 

PMID- 23874240
TI  - Yeast pol4 promotes tel1-regulated chromosomal translocations.
AB  - DNA double-strand breaks (DSBs) are one of the most dangerous DNA lesions, since
      their erroneous repair by nonhomologous end-joining (NHEJ) can generate harmful
      chromosomal rearrangements. PolX DNA polymerases are well suited to extend DSB
      ends that cannot be directly ligated due to their particular ability to bind to
      and insert nucleotides at the imperfect template-primer structures formed during
      NHEJ. Herein, we have devised genetic assays in yeast to induce simultaneous DSBs
      in different chromosomes in vivo. The repair of these breaks in trans could
      result in reciprocal chromosomal translocations that were dependent on classical
      Ku-dependent NHEJ. End-joining events leading to translocations were mainly based
      on the formation of short base pairing between 3'-overhanging DNA ends coupled to
      gap-filling DNA synthesis. A major proportion of these events were specifically
      dependent on yeast DNA polymerase Pol4 activity. In addition, we have discovered
      that Pol4-Thr(540) amino acid residue can be phosphorylated by Tel1/ATM kinase,
      which could modulate Pol4 activity during NHEJ. Our data suggest that the role of
      Tel1 in preventing break-induced chromosomal translocations can, to some extent,
      be due to its stimulating effect on gap-filling activity of Pol4 to repair DSBs
      in cis. Overall, this work provides further insight to the molecular mechanisms
      of DSB repair by NHEJ and presents a new perspective to the understanding of how
      chromosomal translocations are formed in eukaryotic cells. 

PMID- 23874241
TI  - An elegans Solution for Crossover Formation.

PMID- 23874242
TI  - Lixivaptan - an evidence-based review of its clinical potential in the treatment
      of hyponatremia.
AB  - Hyponatremia is the most common electrolyte abnormality seen in clinical
      practice. Most cases of euvolemic or hypervolemic hyponatremia involve arginine
      vasopressin (AVP). AVP leads to a concentrated urine and negative free water
      clearance. Given this primary role of AVP, antagonizing its effect through
      blockade of its receptor in the distal tubule is an attractive therapeutic
      target. Lixivaptan is a newer, non-peptide, vasopressin type 2 receptor
      antagonist. Recent studies have demonstrated efficacy. This review summarizes the
      clinical pharmacology and data for this new agent. 

PMID- 23874243
TI  - Letter from the editor.

PMID- 23874244
TI  - Treatment of two-part proximal humerus fractures: intramedullary nail compared to
      locked plating.
AB  - BACKGROUND: Two-part proximal humerus fractures are common orthopedic injuries
      for which surgical intervention is often indicated. Choosing a fixation device
      remains a topic of debate. PURPOSE: The purpose of this study is to compare two
      methods of fixation for two-part proximal humerus fractures, locking plate (LP)
      with screws versus intramedullary nailing (IMN), with respect to alignment,
      healing, patient outcomes, and complications. To our knowledge, a direct
      comparison of these two devices in treating two-part proximal humerus fractures
      has never before been studied. We hope that our results will help surgeons assess
      the utility of LP versus IMN. METHODS: A retrospective chart review was performed
      on 24 cases of displaced two-part surgical neck fractures of the humerus. Twelve
      shoulders were treated using IMN fixation and 12 others were fixated with LP.
      Data collected included sociodemographic, operative details, and postoperative
      care and function. RESULTS: Radiographic comparison of fixation demonstrated an
      average neck-shaft angle of 124 degrees  and 120 degrees  in the IMN group and LP
      group, respectively. Adjusted postoperative 6-month follow-up range of motion was
      134 degrees  of forward elevation in the IMN group and 141 in the LP group. The
      differences in range of motion and in complication rates were not found to be
      significant. CONCLUSIONS: Our results suggest that either LP fixation or IMN
      fixation for a two-part proximal humerus fracture provides acceptable fixation
      and results in a similar range of shoulder motion. Although complication rates
      were low and insignificant between the two groups, a trend toward increased
      complications in the IMN group is noted.

PMID- 23874245
TI  - MRI diagnosis of patellar clunk syndrome following total knee arthroplasty.
AB  - BACKGROUND: Patellar Clunk Syndrome is a painful condition associated with a
      mechanical catching or clunking during active extension following total knee
      arthroplasty (TKA). The syndrome is caused by growth of interposing soft tissue
      usually at the superior pole of the patella. This interposed soft tissue cannot
      be visualized on plain radiographs. QUESTIONS: The aim was to ascertain if
      magnetic resonance imaging (MRI) would prove helpful in confirming the clinical
      diagnosis of patellar clunk by visualizing the interposed soft tissues adjacent
      to the patella and that the recognition of this tissue would be highly
      reproducible. METHODS: MRI scans of 12 patients with clinical suspicion or
      related symptoms of a patellar clunk syndrome following primary TKA were
      retrospectively evaluated. Size of soft tissue masses proximal to the patella
      were determined in sagittal and axial MRI views. Largest diameters were recorded
      in two dimensions by two independent observers, and interobserver reliability was
      determined by intra-class correlation coefficients (ICC). RESULTS: Nine patients
      (75%) showed obvious MRI findings consistent with a patellar clunk lesion with
      high interobserver reliability (ICC values >0.75). In eight patients, this lead
      to operative treatment with arthroscopic debridement. DISCUSSION: MRI helps
      confirm the clinical diagnosis of patellar clunk. The data indicate that MRI is
      effective in defining the soft tissue lesion that is implicated in clinically
      evident patellar clunk syndrome after TKA.

PMID- 23874246
TI  - Clinical results and failure mechanisms of a nonmodular constrained knee without
      stem extensions.
AB  - INTRODUCTION: In the setting of persistent knee instability despite appropriate
      ligament balancing for primary total knee arthroplasty, most surgeons advocate
      the use of an implant with increased articular constraint. These implants are
      commonly supplemented with stem extensions to improve stress transfer and
      decrease the risk of aseptic loosening. However, disadvantages exist with the use
      of stem extensions, including increased cost, intramedullary invasion, and
      diaphyseal pain. The objectives of this study were to (1) compare the clinical
      results as assessed by the Knee Society, Hospital for Special Surgery, and SF-12
      scores, (2) determine the incidence of failure as defined by the need for a
      revision procedure, and (3) to analyze the causes or modes of failure of a
      nonmodular constrained condylar knee without the use of stem extensions versus a
      conventional, posterior-stabilized design. MATERIALS AND METHODS: From 2002 to
      2007, 190 TKAs were implanted using a primary, nonmodular constrained (NMC)
      prosthesis without stem extensions. During the same time period, clinical data
      were available for 140 TKAs implanted using a standard, posterior-stabilized (PS)
      design. Preoperative demographic data was reviewed, in addition to the rate and
      reason for revision in each cohort. Clinical data included HSS, Knee Society, and
      SF-12 scores at the latest follow-up, and the results of the NMC and PS cohorts
      were statistically compared using a Student's two-tailed t test. RESULTS: The
      mean age of patients in the NMC cohort was 72.3 +/- 10.2 years, and the mean
      length of follow-up was 7.3 +/- 2.1 years. The mean age of the PS cohort was 67.1
      +/- 8.7 years, with a mean follow-up of 6.1 +/- 2.2 years. No statistically
      significant differences in the HSS, Knee Society, or SF-12 scores were
      appreciated between the two cohorts. The revision rate in the NMC cohort was 4.2
      % compared to 4.3 % for the PS cohort. The most common cause of failure in the
      NMC cohort was femoral component loosening, all of which occurred when Palacos
      cement was used for fixation. NMC components (55.6 %) implanted with Palacos
      cement failed due to femoral component loosening. In contrast, all PS components
      requiring revision were revised for persistent instability. DISCUSSION: At mid
      term follow-up, NMC prostheses without stem extensions have excellent clinical
      results and are a viable option for patients with ligamentous instability. The
      use of Palacos cement in this scenario was associated with a high rate of femoral
      component loosening, possibly due to the decreased intrusion depth of Palacos
      when compared to Simplex cement.

PMID- 23874247
TI  - Management strategy for symptomatic bisphosphonate-associated incomplete atypical
      femoral fractures.
AB  - BACKGROUND: Long-term bisphosphonate use has often been associated with atypical
      femoral fractures. These fractures evolve from incomplete femoral fractures. A
      previous study demonstrated that the presence of a radiolucent line in an
      incomplete fracture can indicate a high risk of progression to complete fracture.
      QUESTIONS/PURPOSES: The aim of this study is to present a management strategy for
      symptomatic bisphosphonate-associated incomplete atypical femoral fractures.
      Specific study questions include the following: (1) Is there a difference in the
      prognosis of these fractures based on the presence or absence of a radiolucent
      fracture line? (2) Can treatment with teriparatide assist in
      clinical/radiographic healing of these incomplete fractures? (3) Is there a
      characteristic biochemical profile in these patients? PATIENTS AND METHODS: We
      retrospectively examined all femur radiographs ordered by the metabolic bone
      disease service at our hospital between July 1, 2006 and July 1, 2011 and
      identified 10 patients with a total of 14 incomplete fractures. Nine patients
      received bisphosphonates for a mean duration of 10 +/- 5 years (range, 4-17). The
      mean follow-up since the time of diagnosis was 20 +/- 11 months (range, 6-36
      months). RESULTS: Five fractures did not have a radiolucent fracture line and
      were treated conservatively with partial weight-bearing restrictions and
      pharmacologic therapy. All five of these fractures healed with conservative
      management. Nine fractures had a radiolucent fracture line, and only two of these
      were treated successfully with conservative management including teriparatide.
      Six of the eight patients with a radiolucent line elected for surgical
      prophylaxis after 3 months of conservative management, whereas one patient
      underwent surgical prophylaxis without a trial of conservative management.
      Regarding the biochemical profiles, bone turnover markers for our patient cohort
      were in the lower quartile. CONCLUSIONS: Fractures without a radiolucent line
      appear to respond to conservative management and not require surgical
      prophylaxis. Teriparatide treatment may hold promise in promoting healing of
      these fractures.

PMID- 23874248
TI  - Risk Factor Analysis for 30-Day Mortality After Primary THA in a Single
      Institution.
AB  - The purpose of this study was to determine the prevalence of, and associated risk
      factors for, 30-day perioperative death following primary total hip arthroplasty
      (THA). Data of all the patients were compiled from the computerized total joint
      registry at a single institution. Between May 1993 and May 2006, 3,232
      consecutive primary THA (2,453 elective and 779 nonelective) were performed.
      Eleven deaths occurred during the first month after surgery (0.34 %). Thirty-day
      mortality rate after elective THA was 0.08 % (two of 2,453 IC 95 %(0-0.4)). The
      30-day mortality rate after nonelective THA was 1.15 % (nine of 779 IC 95 %(0.7
      2.4). To analyze the factors that could have contributed with death, we conducted
      a 4-to-1 nested case-control study. Control cases were strictly matched by sex,
      age, surgeon, prosthesis fixation mode, and date of surgery. Conditional logistic
      regression was used to evaluate the association of risk factors with mortality.
      Elective surgery was associated with a lower risk of mortality with an odds ratio
      (OR) of 0.07 (95 % CI 0.008-0.6);p = 0.015. American Society of Anesthesiologists
      (ASA) score III-IV increased the mortality risk 13 times (OR 13.7; 95 % CI 1.6
      114.8). Cardiovascular disease increased the risk for mortality eight times (OR
      8.83 (95 % CI 1.78-43.6). Time delay before surgery showed a trend towards
      significance (p = 0.06). Aggressive vs. nonaggressive thromboembolism prophylaxis
      and the amount of blood transfusions required were not associated with a higher
      risk of death. Patients undergoing a THA due to fractures, patients with high ASA
      score, and those with cardiovascular disease were the highest risk factors for 30
      day mortality after primary THA. 

PMID- 23874249
TI  - Axial lumbosacral interbody fusion appears safe as a method to obtain lumbosacral
      arthrodesis distal to long fusion constructs.
AB  - BACKGROUND: Current methods to achieve lumbosacral interbody fusion have been
      complicated by approach-related morbidity, nerve root or cauda equina injury, or
      difficulty in implanting a large lordotic graft posteriorly. There is little
      information in the literature evaluating the presacral axial approach to the
      lumbosacral disc space. QUESTIONS/PURPOSES: What are the short-term clinical and
      radiographic outcomes in patients undergoing axial lumbosacral interbody fixation
      and fusion at the end of long fusion constructs using the AxiaLIF implant (Trans1
      Inc., Wilmington, NC, USA)? Furthermore, what complications are associated with
      this procedure? PATIENTS AND METHODS: We performed a retrospective evaluation of
      nine patients who underwent presacral axial lumbosacral interbody fixation and
      fusion at the end of long fusion constructs using the AxiaLIF implant.
      Preoperative diagnoses included adjacent segment degeneration below a long fusion
      construct for adult scoliosis and progressive sagittal plane deformity. RESULTS:
      There were two pseudoarthroses, one at L4-5 and one at L5-S1. No major
      complications occurred. There were no significant differences in coronal or
      sagittal plane alignment at the time periods measured. There was no significant
      difference in implant position between immediate postoperative and final follow
      up periods. There were significant postoperative improvements in Scoliosis
      Research Society-22 scores, specifically in the pain, self-image, and
      satisfaction with management domains. CONCLUSIONS: The axial lumbosacral
      interbody fusion is a minimally invasive and safe method to obtain lumbosacral
      fixation and arthrodesis distal to a long fusion construct. Longer follow-up of
      larger numbers of patients are needed prior to recommending this procedure as a
      routine method to fuse L4-5 or L5-S1.

PMID- 23874250
TI  - Anterior elongation as a minimally invasive alternative for sagittal imbalance-a
      case series.
AB  - BACKGROUND: Degenerative and iatrogenic conditions may lead to flat back or even
      to kyphotic deformity, and sagittal imbalance can cause significant clinical
      impairment. Minor imbalance cases are usually treated with conservative care.
      Among currently popular surgical techniques for the correction of sagittal
      imbalance are posterior-based procedures, which are associated with access
      related risks (mostly neurological) and postoperative morbidity risks. PURPOSE:
      This study aims to report a minimally invasive lateral approach using
      hyperlordotic cages in the treatment of mild sagittal imbalance. Radiological
      correction, clinical improvement, and safety will be analyzed. METHODS: Eight
      patients (mean age 71.8 years, SD 7.8; mean BMI 27.5, SD 2.3) with symptomatic
      sagittal imbalance were retrospectively reviewed. Eight cases were treated by
      anterior interbody fusion with lordotic cages. A minimally invasive lateral
      retroperitoneal approach was used in the surgical procedures, with or without
      percutaneous pedicle screw supplementation. RESULTS: No major complications
      occurred and just one case needed revision for direct decompression. Clinical
      outcomes Visual Analog Scale score changed from 88 at preoperative visit to 51 at
      1-week visit, and Oswestry Disability Index score decreased from 82 at
      preoperative visit to 44 at 6-week visit. The 6-month radiological assessment
      revealed improvement in spinopelvic parameters: Focal lordosis improved from 2.3
      degrees  +/- 7.7 to 27.1 degrees  +/- 6.7. Sagittal vertical alignment improved
      from 11.7 +/- 5.3 to 6.2 +/- 4.0 cm. Preoperative sacral slope improved from 20.1
      degrees  +/- 5.8 to 29.4 degrees  +/- 10.3 and preoperative pelvic tilt improved
      from 35.2 degrees  +/- 5.2 to 23.8 degrees  +/- 4.3. Short-term results indicate
      that the minimally invasive lateral approach can be applied to the treatment of
      mild sagittal imbalance, with special advantage in elderly patients or those in
      which posterior approaches are relatively contraindicated.

PMID- 23874252
TI  - In vitro elution characteristics of vancomycin in a composite calcium
      phosphate/calcium sulfate bone substitute.
AB  - BACKGROUND: Periprosthetic joint infection is a particularly difficult orthopedic
      problem, complicating a growing number of revision procedures. Joint debridement
      and systemic antibiotics are the mainstay of treatment, yet difficulty remains in
      maintaining a minimum inhibitory concentration of antibiotic at the localized
      site of infection. STUDY AIMS: This study analyzes the elution characteristics of
      a 40%bwt calcium phosphate-60%bwt calcium sulfate composite, at varying
      concentrations of vancomycin. METHODS: Four groups of varying concentrations of
      vancomycin (2.63%bwt, 5.13%, 9.76%, and 17.78%) were mixed with one pack of the
      composite cement. At designated time intervals up to 28 days, the antibiotic
      concentration was detected using fluorescence polarization immunoassay and the
      elution trends compared. RESULTS: The elution rate of each of the four groups
      decreased over time. At almost all of the intervals, the elution rates of the
      higher concentration groups were significantly higher than the lower
      concentration groups (P < 0.05). CONCLUSIONS: Calcium sulfate reabsorbs over a
      prolonged period, producing porosity which allows for new bone ingrowth through
      occupation of osteoprogenitor cells and osteoblasts; while calcium phosphate acts
      as a long-term osteoconductive matrix. CLINICAL RELEVANCE: The results of this
      study suggest that vancomycin can be mixed affectively with a calcium
      sulfate/phosphate composite, both maintaining stability and eluting gradually
      over a clinically relevant period of time.

PMID- 23874253
TI  - Regional anesthesia for children undergoing orthopedic ambulatory surgeries in
      the United States, 1996-2006.
AB  - BACKGROUND: Our objective was to evaluate national trends in regional anesthetic
      techniques among children undergoing ambulatory orthopedic procedures. PURPOSE
      AND QUESTIONS: We aimed to determine whether an increase in regional anesthetics
      was primarily driven by an increase in the number of peripheral nerve blocks
      performed rather than an increase in neuraxial techniques. We further aimed to
      determine whether the proportion of peripheral nerve blocks performed in
      conjunction with general anesthesia has increased over time. PATIENTS AND
      METHODS: Our study sample included any pediatric patient (i.e., <18 years old)
      who underwent an orthopedic ambulatory procedure in 1996 and 2006. We obtained
      data on ambulatory surgical procedures by accessing the Centers for Disease
      Control and Prevention's National Survey of Ambulatory Surgery. Patient
      demographics (age, gender), procedure information, and anesthesia-related
      variables were analyzed for each year. RESULTS: The proportion of peripheral
      nerve blocks performed for ambulatory surgery more than doubled from 1996 (4.4 %)
      to 2006 (8.1 %). A significantly larger proportion of orthopedic procedures were
      being performed with a combination of peripheral nerve blocks and general
      anesthesia (1.2 % in 1996 and 43 % 2006). The use of neuraxial anesthesia for
      lower extremity surgeries decreased over the 10-year period (1.1 and 0.4 % in
      1996 and 2006, respectively). CONCLUSIONS: There was a significant increase in
      the use of peripheral nerve blocks for children undergoing ambulatory orthopedic
      procedures in the USA, while neuraxial techniques became less common over the 10
      year period. The peripheral nerve blocks were frequently performed in conjunction
      with general anesthesia.

PMID- 23874254
TI  - The role of platelet-rich plasma in inducing musculoskeletal tissue healing.
AB  - BACKGROUND: Platelet-rich plasma [PRP] has received increasing interest across
      many musculoskeletal disciplines and has been widely applied clinically to
      stimulate tissue healing in numerous anatomical regions. The known actions of
      platelet-derived factors suggest that PRP may have significant potential in the
      treatment of pathological conditions of cartilage, tendon, ligament, and muscle.
      PURPOSE: The aim of this manuscript is to review current literature regarding the
      biology of PRP and the efficacy of using PRP to augment healing of tendon
      ligament and muscle injuries, as well as early osteoarthritis. METHODS: A
      comprehensive literature review of musculoskeletal applications of PRP was
      performed, including basic science and clinical studies such as randomized
      controlled trials, case controlled series, and case series. RESULTS: The most
      compelling evidence to support the efficacy of PRP is for its application to
      tendon damage associated with lateral and medial epicondylitis. Although some
      promising studies have been reported supporting the use of PRP in osteoarthritis
      and ligament and muscle injuries, it currently remains unknown whether PRP
      effectively alters the progression of osteoarthritis or aids the healing of
      ligament and muscle tissues. CONCLUSION: The rationale for the use of PRP to
      improve tissue healing is strong, but the efficacy for many musculoskeletal
      applications remains unproven. PRP has been shown to be a safe treatment. A
      number of questions regarding PRP remain unanswered, including the optimal
      concentration of platelets, what cell types should be present, the ideal
      frequency of application, or the optimal rehabilitation regimen for tissue repair
      and return to full function.

PMID- 23874255
TI  - Total hip arthroplasty at the rothman institute.
AB  - BACKGROUND: Total hip arthroplasty (THA) is one of the most successful surgical
      interventions devised in modern times. Attempts to change the current THA
      procedure with unproven innovations bring the risk of increased failure rates
      while trying to improve the benefit of the surgery. QUESTIONS/PURPOSES: This
      manuscript examines the evolution of THA at the Rothman Institute illustrating
      the key elements that lead the success of this procedure at this institution.
      These key elements include femoral stem design, use of highly crossed-linked
      polyethylene and use of pain and rehabilitation protocols. We attempted to
      describe the long-term results regarding safety, effectiveness, and durability of
      specific THA implant designs used at this institution drawing on reported
      evidence in the literature. METHODS: The authors performed a review of peer
      reviewed articles related to the Rothman Institute's experience with THA.
      RESULTS: Total hip arthroplasty is an efficient, safe, and durable procedure. It
      is a highly successful operation to restore function and improve pain. The
      survivorship of THA procedures at the Rothman Institute is higher than 99% at 10
      years based on mechanical failure. The use of collarless, tapered wedge femoral
      stem, highly crossed-linked polyethylene, and improved pain rehabilitation
      protocols have contributed to this success. CONCLUSIONS: There is a well
      documented long-term survivorship after THA. Future innovation in THA should
      address new challenges with younger and more demanding patients, rather than
      change current methods that have a proven good survivorship. This innovation
      depends mainly upon improvements in the bearing surfaces and advances in pain
      control and rehabilitation.

PMID- 23874256
TI  - The state of the science in the prevention and management of osteoarthritis:
      experts recommend ways to increase nurses' awareness and knowledge of
      osteoarthritis.

PMID- 23874257
TI  - Pharmacologic Management of Osteoarthritis-Related Pain in Older Adults: A Review
      Shows that Many Drug Therapies Provide Small-to-Modest Pain Relief.
AB  - 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- 23874258
TI  - Creating an academy of medical educators: how and where to start.
AB  - BACKGROUND: While most faculty members want to improve as teachers, they neither
      know where their educational strengths and weaknesses lie nor where or how to
      begin to effect a change in their teaching abilities. The lack of actionable,
      directed and specific feedback, and sensible and sensitive metrics to assess
      performance and improvement complicates the attainment of educational excellence.
      PURPOSE: The purpose of this article was to outline a series of specific steps
      that medical education programs can take to enhance the quality of teaching,
      promote teaching excellence, elevate the status and value of medical educators,
      and stimulate the creation of innovative teaching programs and curricula.
      METHODS: To achieve these goals at the Hospital for Special Surgery, the Academy
      of Rheumatology Medical Educators was formed. The academy had the following
      goals: (1) create within our institution a mission which advances and supports
      educators, (2) establish a membership composed of distinguished educators, (3)
      create a formal organizational structure with designated leadership, (4) dedicate
      resources that fund mission-related initiatives and research, and (5) establish a
      plan for promoting teachers as well as enhancing and advancing educational
      scholarship. RESULTS: The Hospital for Special Surgery Academy of Rheumatology
      Medical Educators was recently formed to address these goals by promoting
      teaching and learning of musculoskeletal skills in an environment that is
      supportive to educators and trainees and provides much needed resources for
      teachers. SUMMARY: The development of a pilot academy of medical educators
      represents one of the high-priority goals of those institutions that wish to
      elevate and enrich their teaching through a structured, proven approach.

PMID- 23874259
TI  - A single-dose conformal delivery of radiotherapy following osteoplasty : a novel
      approach to treatment of osteolytic metastasis in the setting of multiple
      myeloma.
AB  - Multiple myeloma (MM) is a very radiosensitive tumor. Fractionated external beam
      radiation, which takes approximately 2 weeks of therapy, is typically used to
      irradiate myelomatous bone lesions with the goal of palliation. However,
      traditional radiotherapeutic techniques are not only lengthy but they also
      involve a considerable amount of healthy bone marrow in the treatment ports,
      which may undermine the total marrow reserve of a patient. Because of the limited
      survival time of patients with metastatic cancer, novel treatment concepts
      shortening the overall treatment time is desirable. We present an innovative
      approach of delivering targeted intra-operative radiotherapy to a solitary
      osteolytic metastasis in one application, while sparing healthy bone marrow from
      radiation toxicity and substantially reducing the overall treatment time. A 78
      year-old Caucasian male with MM, previously treated with chemotherapy, who was
      off chemotherapy for 2 years due to bone marrow suppression, presented with a
      solitary recurrence at the left anterior superior iliac spine of the left iliac
      wing as diagnosed by PET-CT scan. This lesion was treated with a minimally
      invasive osteoplasty and intra-operative brachytherapy with to a dose of 8 Gy
      delivered to the surgical cavity only, followed by injection of the bone cement
      into the cavity. Three months after the procedure, the area of treatment
      demonstrated no uptake on a follow-up PET-CT scan. At 1.5 years after this
      procedure, 100% local control continues to persist in the treated area, as
      evidenced on nuclear imaging. To our knowledge, this is the first case of using
      focal intra-operative brachytherapy confined to the area of the pelvis in a
      patient treated for a solitary metastasis from MM. The purpose of the article is
      to present a novel approach as a more convenient and focal treatment of bony
      lesions of MM. 

PMID- 23874260
TI  - Cardiac Arrest during Total Hip Arthroplasty in a Patient on an Angiotensin
      Receptor Antagonist.
AB  - Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor
      antagonists (ARA) are effective and well-tolerated first-line drugs in the
      therapy of hypertension and, therefore, are frequently encountered in the
      perioperative setting. Hemodynamic compensation for volume depletion seen in the
      perioperative period is normally mediated by the renin-angiotensin system, which
      is blocked by ACEI/ARA. These drugs may contribute to severe hypotension during
      anesthesia induction and may have contributed to the cardiac arrest seen in this
      patient. Additional factors such as increased intra-abdominal pressures and
      respiratory obstructive episodes leading to diminished venous return, as well
      diuretic use and the fasting state, common in the perioperative orthopedic
      patient, are likely to have contributed as well. Medication use may be an easily
      modifiable risk factor for severe hypotension and possible cardiac arrest in the
      perioperative setting. 

PMID- 23874261
TI  - Posterior interosseous neuropathy: electrodiagnostic evaluation.
AB  - Electrodiagnostic studies are used to anatomically localize nerve injuries. These
      tests help differentiate between cervical radiculopathies, brachial plexopathies,
      and peripheral nerve injuries. They also help to identify or rule out other
      underlying neurological diseases and disorders. In this case report, a 22-year
      old male swimmer presented with left finger extensor weakness following pull-up
      exercises. Left wrist extension remained intact. Electrodiagnostic testing
      revealed a severe but incomplete posterior interosseous neuropathy. Magnetic
      resonance imaging confirmed inflammation of the nerve in the forearm. Posterior
      interosseous neuropathy is an uncommon but well-studied condition. Typically,
      this condition presents with weakness in finger and thumb extension with
      preserved wrist extension as the extensor carpi radialis longus is innervated
      proximal to the site of nerve compression in most cases. It is important to
      understand the anatomic course and distribution of the radial nerve in order to
      make an accurate diagnosis. Once the anatomy is understood, electrodiagnostic
      testing may be used to identify the location of nerve injury and exclude other
      disorders. 

PMID- 23874262
TI  - Liver abscesses after peritoneal venous shunt.
AB  - A 70-year-old man was referred to our hospital for high-grade fever with chills.
      He has visited our hospital for alcoholic liver cirrhosis and diabetes mellitus
      for over 20 years. Nine months earlier, he had received a peritoneal venous shunt
      (Denver shunt(r)) because of refractory ascites. Laboratory examinations revealed
      elevated C-reactive protein and liver dysfunction. Ultrasonography and abdominal
      enhanced computed tomography showed multiple small abscesses in the right lobe of
      the liver. Blood culture test did not detect the pathogenic bacteria of liver
      abscesses. The patient was treated with antibiotics for more than 2 months and
      cured from the infection, but 3 months later, he developed high-grade fever
      again. He had a recurrence of multiple small liver abscesses involving both lobes
      of the liver. He was treated with antibiotics, and the abscesses disappeared
      within a month. After the antibiotic treatment, he had selective intestinal
      decontamination with kanamycin. He has had no recurrence of liver abscess for
      over a year. To our knowledge, this is the first report of liver abscess in a
      cirrhotic patient with Denver shunt. Clinicians should bear liver abscess in mind
      when treating patients with high-grade fever and liver dysfunction following
      Denver shunt implantation. 

PMID- 23874263
TI  - Survival after resection of a primary malignant melanoma of the small intestine
      in a young patient: report of a case.
AB  - The occurrence of primary melanoma of the small intestine is rare. We describe
      the case of a 25-year-old man found to have a primary melanoma of the ileum. The
      patient presented with gradual onset of abdominal pain, fever, diarrhea, weight
      loss and fatigue. A preoperative diagnosis of a small intestinal tumor was based
      on the findings of computed tomography scanning. This diagnosis was confirmed at
      laparoto-my and a partial small bowel resection was performed. Histopathological
      examination of the resected specimen clarified the exact nature of the lesion,
      confirming the diagnosis of melanoma. Thorough postoperative investigation did
      not reveal a primary lesion in the skin, gastrointestinal tract, oculus or brain.
      Thus, we diagnosed this tumor as a primary lesion. One year after his operation,
      the patient remains well without any evidence of recurrence. Thus, we diagnosed
      this small bowel tumor as a primary melanoma of the small intestine. 

PMID- 23874264
TI  - Use of diagnostic laparoscopy in a patient with gastric pneumatosis and portal
      venous gas.
AB  - Gastric pneumatosis is a radiographic finding that represents a spectrum of
      conditions ranging from benign disease to abdominal sepsis and death. Along with
      portal venous gas, it is generally considered an ominous sign prompting emergent
      operative intervention. We report a rare case showing that diagnostic laparoscopy
      can be used to confirm or refute full thickness ischemic necrosis and that
      conservative management can be considered in some patients, recognizing the
      possibility of a benign process. 

PMID- 23874266
TI  - The neuropharmacology of the age-old sedative/hypnotic, ethanol.

PMID- 23874265
TI  - Rapid processing of chemosensor transients in a neuromorphic implementation of
      the insect macroglomerular complex.
AB  - We present a biologically-constrained neuromorphic spiking model of the insect
      antennal lobe macroglomerular complex that encodes concentration ratios of
      chemical components existing within a blend, implemented using a set of
      programmable logic neuronal modeling cores. Depending upon the level of
      inhibition and symmetry in its inhibitory connections, the model exhibits two
      dynamical regimes: fixed point attractor (winner-takes-all type), and limit cycle
      attractor (winnerless competition type) dynamics. We show that, when driven by
      chemosensor input in real-time, the dynamical trajectories of the model's
      projection neuron population activity accurately encode the concentration ratios
      of binary odor mixtures in both dynamical regimes. By deploying spike timing
      dependent plasticity in a subset of the synapses in the model, we demonstrate
      that a Hebbian-like associative learning rule is able to organize weights into a
      stable configuration after exposure to a randomized training set comprising a
      variety of input ratios. Examining the resulting local interneuron weights in the
      model shows that each inhibitory neuron competes to represent possible ratios
      across the population, forming a ratiometric representation via mutual
      inhibition. After training the resulting dynamical trajectories of the projection
      neuron population activity show amplification and better separation in their
      response to inputs of different ratios. Finally, we demonstrate that by using
      limit cycle attractor dynamics, it is possible to recover and classify blend
      ratio information from the early transient phases of chemosensor responses in
      real-time more rapidly and accurately compared to a nearest-neighbor classifier
      applied to the normalized chemosensor data. Our results demonstrate the potential
      of biologically-constrained neuromorphic spiking models in achieving rapid and
      efficient classification of early phase chemosensor array transients with
      execution times well beyond biological timescales. 

PMID- 23874267
TI  - Detection of dopamine neurotransmission in "real time".
AB  - Current imaging techniques have limited ability to detect neurotransmitters
      released during brain processing. It is a critical limitation because
      neurotransmitters have significant control over the brain activity. In this
      context, recent development of single-scan dynamic molecular imaging technique is
      important because it allows detection, mapping, and measurement of dopamine
      released in the brain during task performance. The technique exploits the
      competition between endogenously released dopamine and its receptor ligand for
      occupancy of receptor sites. Dopamine released during task performance is
      detected by dynamically measuring concentration of intravenously injected
      radiolabeled ligand using a positron emission tomography (PET) camera. Based on
      the ligand concentration, values of receptor kinetic parameters are estimated.
      These estimates allow detection of dopamine released in the human brain during
      task performance. 

PMID- 23874268
TI  - Synaptic vesicle capture by CaV2.2 calcium channels.
AB  - The fusion of synaptic vesicles (SVs) at the presynaptic transmitter release face
      is gated by Ca(2) (+) influx from nearby voltage-gated calcium channels (CaVs).
      Functional studies favor a direct molecular "tethering" attachment and recent
      studies have proposed a direct link to the channel C-terminal. To test for direct
      CaV-SV attachment we developed an in vitro assay, termed SV pull-down (SV-PD), to
      test for capture of purified, intact SVs. Antibody-immobilized presynaptic or
      expressed CaV2.2 channels but not plain beads, IgG or pre-blocked antibody
      successfully captured SVs, as assessed byWestern blot for a variety of protein
      markers. SV-PD was also observed with terminal fusion proteins of the distal half
      of the C-terminal, supporting involvement of this CaV region in tethering. Thus
      our results support a model in which the SV tethers directly to the CaV. Since
      the tip of the C-terminal could extend as far as 200 nm into the cytoplasm, we
      hypothesize that this link may serve as the initial SV capture mechanism by the
      release site. Further studies will be necessary to evaluate the molecular basis
      of C-terminal tethering and whether the SV binds to the channel by additional,
      shorter-range attachments. 

PMID- 23874269
TI  - Changes in the sensitivity of GABAA current rundown to drug treatments in a model
      of temporal lobe epilepsy.
AB  - The pharmacological treatment of mesial temporal lobe epilepsy (mTLE), the most
      common epileptic syndrome in adults, is still unsatisfactory, as one-third of the
      patients are or become refractory to antiepileptic agents. Refractoriness may
      depend upon drug-induced alterations, but the disease per se may also undergo a
      progressive evolution that affects the sensitivity to drugs. mTLE has been shown
      to be associated with a dysfunction of the inhibitory signaling mediated by GABAA
      receptors. In particular, the repetitive activation of GABAA receptors produces a
      use-dependent decrease (rundown) of the evoked currents (I GABA), which is
      markedly enhanced in the hippocampus and cortex of drug-resistant mTLE patients.
      This phenomenon has been also observed in the pilocarpine model, where the
      increased I GABA rundown is observed in the hippocampus at the time of the first
      spontaneous seizure, then extends to the cortex and remains constant in the
      chronic phase of the disease. Here, we examined the sensitivity of I GABA to
      pharmacological modulation. We focused on the antiepileptic agent levetiracetam
      (LEV) and on the neurotrophin brain-derived neurotrophic factor (BDNF), which
      were previously reported to attenuate mTLE-induced increased rundown in the
      chronic human tissue. In the pilocarpine model, BDNF displayed a paramount
      effect, decreasing rundown in the hippocampus at the time of the first seizure,
      as well as in the hippocampus and cortex in the chronic period. In contrast, LEV
      did not affect rundown in the hippocampus, but attenuated it in the cortex.
      Interestingly, this effect of LEV was also observed on the still unaltered
      rundown observed in the cortex at the time of the first spontaneous seizure.
      These data suggest that the sensitivity of GABAA receptors to pharmacological
      interventions undergoes changes during the natural history of mTLE, implicating
      that the site of seizure initiation and the timing of treatment may highly affect
      the therapeutic outcome. 

PMID- 23874270
TI  - The unimodal distribution of sub-threshold, ongoing activity in cortical
      networks.
AB  - The characterization of the subthreshold, ongoing activity in cortical neurons
      has been the focus of numerous studies. This activity, described as spontaneous
      slow waves in membrane potential, has been observed in a span of species in
      diverse cortical and subcortical areas. We here characterized membrane potential
      fluctuations in motor and the frontal association cortices cortical neurons of
      ketamine-xylazine anesthetized rats. We recorded from 95 neurons from a range of
      cortical depths to unravel the network and cellular mechanisms that shape the
      subthreshold ongoing spontaneous activity of these neurons. We define a unitary
      event that generates the subthreshold ongoing activity: giant synaptic potentials
      (GSPs). These events have a duration of 87 +/- 50 ms and an amplitude of 19 +/-
      6.4 mV. They occur at a frequency of 3.7 +/- 0.8 Hz and involve an increase in
      conductance change of 22 +/- 21%. GSPs are mainly due to excitatory activity that
      occurs throughout all cortical layers, unaffected by the intrinsic properties of
      the cells. Indeed, blocking the GABAA receptors, a procedure that had a profound
      effect on cortical activity, did not alter these unitary events. We propose that
      this unitary event is composed of individual, excitatory synaptic potentials that
      appear at different levels of synchrony and that the level of synchrony
      determines the shape of the subthreshold activity. 

PMID- 23874271
TI  - Tonotopic organization of the hyperpolarization-activated current (Ih) in the
      mammalian medial superior olive.
AB  - Neuronal membrane properties can largely vary even within distinct morphological
      cell classes. The mechanisms and functional consequences of this diversity,
      however, are little explored. In the medial superior olive (MSO), a brainstem
      nucleus that performs binaural coincidence detection, membrane properties at rest
      are largely governed by the hyperpolarization-activated inward current (Ih) which
      enables the temporally precise integration of excitatory and inhibitory inputs.
      Here, we report that Ih density varies along the putative tonotopic axis of the
      MSO with Ih being largest in ventral, high-frequency (HF) processing neurons.
      Also Ih half-maximal activation voltage and time constant are differentially
      distributed such that Ih of the putative HF processing neurons activate faster
      and at more depolarized levels. Intracellular application of saturating
      concentrations of cyclic AMP removed the regional difference in hyperpolarization
      activated cyclic nucleotide gated (HCN) channel activation, but not Ih density.
      Experimental data in conjunction with a computational model suggest that
      increased Ih levels are helpful in counteracting temporal summation of phase
      locked inhibitory inputs which is particularly prominent in HF neurons. 

PMID- 23874272
TI  - The first mecp2-null zebrafish model shows altered motor behaviors.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disorder and one of the
      most common causes of mental retardation in affected girls. Other symptoms
      include a rapid regression of motor and cognitive skills after an apparently
      early normal development. Sporadic mutations in the transcription factor MECP2
      has been shown to be present in more than 90% of the patients and several models
      of MeCP2-deficient mice have been created to understand the role of this gene.
      These models have pointed toward alterations in the maintenance of the central
      nervous system rather than its development, in line with the late onset of the
      disease in humans. However, the exact functions of MeCP2 remain difficult to
      delineate and the animal models have yielded contradictory results. Here, we
      present the first mecp2-null allele mutation zebrafish model. Surprisingly and in
      contrast to MeCP2-null mouse models, mecp2-null zebrafish are viable and fertile.
      They present nonetheless clear behavioral alterations during their early
      development, including spontaneous and sensory-evoked motor anomalies, as well as
      defective thigmotaxis. 

PMID- 23874273
TI  - The Ease of Language Understanding (ELU) model: theoretical, empirical, and
      clinical advances.
AB  - Working memory is important for online language processing during conversation.
      We use it to maintain relevant information, to inhibit or ignore irrelevant
      information, and to attend to conversation selectively. Working memory helps us
      to keep track of and actively participate in conversation, including taking turns
      and following the gist. This paper examines the Ease of Language Understanding
      model (i.e., the ELU model, Ronnberg, 2003; Ronnberg et al., 2008) in light of
      new behavioral and neural findings concerning the role of working memory capacity
      (WMC) in uni-modal and bimodal language processing. The new ELU model is a
      meaning prediction system that depends on phonological and semantic interactions
      in rapid implicit and slower explicit processing mechanisms that both depend on
      WMC albeit in different ways. It is based on findings that address the
      relationship between WMC and (a) early attention processes in listening to
      speech, (b) signal processing in hearing aids and its effects on short-term
      memory, (c) inhibition of speech maskers and its effect on episodic long-term
      memory, (d) the effects of hearing impairment on episodic and semantic long-term
      memory, and finally, (e) listening effort. New predictions and clinical
      implications are outlined. Comparisons with other WMC and speech perception
      models are made. 

PMID- 23874275
TI  - Development in the organization of episodic memories in middle childhood and
      adolescence.
AB  - The basic elements of autobiographical or episodic memory are established in
      early childhood, although the exact age at which memories gain episodic status is
      still under contention. The self-memory system proposed that adults use "lifetime
      periods" to group episodic memories together into chapters of the life story - an
      evolving and internalized account of significant life events that are self
      defining. Two studies examined at what point in development children or
      adolescents begin to take advantage of lifetime-period chapters to organize their
      episodic memories. The results of Study 1 with 8- to 12-year-olds revealed that
      the ability to provide life story chapters began to emerge as early as 8 years of
      age. In Study 2 with adolescents aged 12-21, this ability continued to develop
      into late adolescence among New Zealand European (NZE) and New Zealand Chinese
      (NZC) adolescents; however, cultural differences also existed in the specificity
      of memories. NZC adolescents narrated fewer life story chapters containing
      specific memories than NZE adolescents. These findings support and extend current
      theories of episodic memory by specifying that pre-adolescents are starting to
      organize their episodic memories into lifetime periods, but this achievement is
      not fully realized until later in adolescence. 

PMID- 23874274
TI  - Missing and Possible Link between Neuroendocrine Factors, Neuropsychiatric
      Disorders, and Microglia.
AB  - Endocrine systems have long been suggested to be one of the important factors in
      neuropsychiatric disorders, while the underlying mechanisms have not been well
      understood. Traditionally, neuropsychiatric disorders have been mainly considered
      the consequence of abnormal conditions in neural circuitry. Beyond the neuronal
      doctrine, microglia, one of the glial cells with inflammatory/immunological
      functions in the central nervous system (CNS), have recently been suggested to
      play important roles in neuropsychiatric disorders. However, the crosstalk
      between neuroendocrine factors, neuropsychiatric disorders, and microglia has
      been unsolved. Therefore, we herein introduce and discuss a missing and possible
      link between these three factors; especially highlighting the following hormones;
      (1) Hypothalamic-Pituitary-Adrenal (HPA) axis-related hormones such as
      corticotropin-releasing hormone (CRH) and glucocorticoids, (2) sex-related
      hormones such as estrogen and progesterone, and (3) oxytocin. A growing body of
      evidence has suggested that these hormones have a direct effect on microglia. We
      hypothesize that hormone-induced microglial activation and the following
      microglia-derived mediators may lead to maladaptive neuronal networks including
      synaptic dysfunctions, causing neuropsychiatric disorders. Future investigations
      to clarify the correlation between neuroendocrine factors and microglia may
      contribute to a novel understanding of the pathophysiology of neuropsychiatric
      disorders. 

PMID- 23874277
TI  - Unlearning versus savings in visuomotor adaptation: comparing effects of washout,
      passage of time, and removal of errors on motor memory.
AB  - Humans are able to rapidly adapt their movements when a visuomotor or other
      systematic perturbation is imposed. However, the adaptation is forgotten or
      unlearned equally rapidly once the perturbation is removed. The ultimate cause of
      this unlearning remains poorly understood. Unlearning is often considered to be a
      passive process due to inability to retain an internal model. However, we have
      recently suggested that it may instead be a process of reversion to habit,
      without necessarily any forgetting per se. We compared the timecourse and nature
      of unlearning across a variety of protocols where unlearning is known to occur:
      error-clamp trials, removal of visual feedback, removal of the perturbation, or
      simply a period of inactivity. We found that, in agreement with mathematical
      models, there was no significant difference in the rate of decay between subject
      who experienced zero-error clamp trials, and subjects who made movements with no
      visual feedback. Time alone did lead to partial unlearning (over the duration we
      tested), but the amount of unlearning was inconsistent across subjects. Upon re
      exposure to the same perturbation, subjects who unlearned through time or by
      reverting to veridical feedback exhibited savings. By contrast, no savings was
      observed in subjects who unlearned by having visual feedback removed or by being
      placed in a series of error-clamp trials. Thus although these various forms of
      unlearning can all revert subjects back to baseline behavior, they have markedly
      different effects on whether long-term memory for the adaptation is spared or is
      also unlearned. On the basis of these and previous findings, we suggest that
      unlearning is not due to passive forgetting of an internal model, but is instead
      an active process whereby adapted behavior gradually reverts to baseline habits. 

PMID- 23874276
TI  - Behavioral and biochemical evidence of the role of acetaldehyde in the
      motivational effects of ethanol.
AB  - Since Chevens' report, in the early 50's that his patients under treatment with
      the aldehyde dehydrogenase inhibitor, antabuse, could experience beneficial
      effects when drinking small volumes of alcoholic beverages, the role of
      acetaldehyde (ACD) in the effects of ethanol has been thoroughly investigated on
      pre-clinical grounds. Thus, after more than 25 years of intense research, a large
      number of studies have been published on the motivational properties of ACD
      itself as well as on the role that ethanol-derived ACD plays in the effects of
      ethanol. Accordingly, in particular with respect to the motivational properties
      of ethanol, these studies were developed following two main strategies: on one
      hand, were aimed to challenge the suggestion that also ACD may exert motivational
      properties on its own, while, on the other, with the aid of enzymatic
      manipulations or ACD inactivation, were aimed to test the hypothesis that ethanol
      derived ACD might have a role in ethanol motivational effects. Furthermore,
      recent evidence significantly contributed to highlight, as possible mechanisms of
      action of ACD, its ability to commit either dopaminergic and opioidergic
      transmission as well as to activate the Extracellular signal Regulated Kinase
      cascade transduction pathway in reward-related brain structures. In conclusion,
      and despite the observation that ACD seems also to have inherited the elusive
      nature of its parent compound, the behavioral and biochemical evidence reviewed
      points to ACD as a neuroactive molecule able, on its own and as ethanol
      metabolite, to exert motivational effects. 

PMID- 23874278
TI  - The role of auditory transient and deviance processing in distraction of task
      performance: a combined behavioral and event-related brain potential study.
AB  - Distraction of goal-oriented performance by a sudden change in the auditory
      environment is an everyday life experience. Different types of changes can be
      distracting, including a sudden onset of a transient sound and a slight deviation
      of otherwise regular auditory background stimulation. With regard to deviance
      detection, it is assumed that slight changes in a continuous sequence of auditory
      stimuli are detected by a predictive coding mechanisms and it has been
      demonstrated that this mechanism is capable of distracting ongoing task
      performance. In contrast, it is open whether transient detection-which does not
      rely on predictive coding mechanisms-can trigger behavioral distraction, too. In
      the present study, the effect of rare auditory changes on visual task performance
      is tested in an auditory-visual cross-modal distraction paradigm. The rare
      changes are either embedded within a continuous standard stimulation (triggering
      deviance detection) or are presented within an otherwise silent situation
      (triggering transient detection). In the event-related brain potentials, deviants
      elicited the mismatch negativity (MMN) while transients elicited an enhanced N1
      component, mirroring pre-attentive change detection in both conditions but on the
      basis of different neuro-cognitive processes. These sensory components are
      followed by attention related ERP components including the P3a and the
      reorienting negativity (RON). This demonstrates that both types of changes
      trigger switches of attention. Finally, distraction of task performance is
      observable, too, but the impact of deviants is higher compared to transients.
      These findings suggest different routes of distraction allowing for the automatic
      processing of a wide range of potentially relevant changes in the environment as
      a pre-requisite for adaptive behavior. 

PMID- 23874279
TI  - The perils of global signal regression for group comparisons: a case study of
      Autism Spectrum Disorders.
AB  - We have previously argued from a theoretical basis that the standard practice of
      regression of the Global Signal from the fMRI time series in functional
      connectivity studies is ill advised, particularly when comparing groups of
      participants. Here, we demonstrate in resting-state data from participants with
      an Autism Spectrum Disorder and matched controls that these concerns are also
      well founded in real data. Using the prior theoretical work to formulate
      predictions, we show: (1) rather than simply altering the mean or range of
      correlation values amongst pairs of brain regions, Global Signal Regression
      systematically alters the rank ordering of values in addition to introducing
      negative values, (2) it leads to a reversal in the direction of group correlation
      differences relative to other preprocessing approaches, with a higher incidence
      of both long-range and local correlation differences that favor the Autism
      Spectrum Disorder group, (3) the strongest group differences under other
      preprocessing approaches are the ones most altered by Global Signal Regression,
      and (4) locations showing group differences no longer agree with those showing
      correlations with behavioral symptoms within the Autism Spectrum Disorder group.
      The correlation matrices of both participant groups under Global Signal
      Regression were well predicted by our previous mathematical analyses,
      demonstrating that there is nothing mysterious about these results. Finally, when
      independent physiological nuisance measures are lacking, we provide a simple
      alternative approach for assessing and lessening the influence of global
      correlations on group comparisons that replicates our previous findings. While
      this alternative performs less well for symptom correlations than our favored
      preprocessing approach that includes removal of independent physiological
      measures, it is preferable to the use of Global Signal Regression, which prevents
      unequivocal conclusions about the direction or location of group differences. 

PMID- 23874280
TI  - Language repetition and short-term memory: an integrative framework.
AB  - Short-term maintenance of verbal information is a core factor of language
      repetition, especially when reproducing multiple or unfamiliar stimuli. Many
      models of language processing locate the verbal short-term maintenance function
      in the left posterior superior temporo-parietal area and its connections with the
      inferior frontal gyrus. However, research in the field of short-term memory has
      implicated bilateral fronto-parietal networks, involved in attention and serial
      order processing, as being critical for the maintenance and reproduction of
      verbal sequences. We present here an integrative framework aimed at bridging
      research in the language processing and short-term memory fields. This framework
      considers verbal short-term maintenance as an emergent function resulting from
      synchronized and integrated activation in dorsal and ventral language processing
      networks as well as fronto-parietal attention and serial order processing
      networks. To-be-maintained item representations are temporarily activated in the
      dorsal and ventral language processing networks, novel phoneme and word serial
      order information is proposed to be maintained via a right fronto-parietal serial
      order processing network, and activation in these different networks is proposed
      to be coordinated and maintained via a left fronto-parietal attention processing
      network. This framework provides new perspectives for our understanding of
      information maintenance at the non-word-, word- and sentence-level as well as of
      verbal maintenance deficits in case of brain injury. 

PMID- 23874281
TI  - Neurophysiological constraints on the eye-mind link.
AB  - Several current computational models of eye-movement control in reading posit a
      tight link between the eye and mind, with lexical processing directly triggering
      most "decisions" about when to start programming a saccade to move the eyes from
      one word to the next. One potential problem with this theoretical assumption,
      however, is that it may violate neurophysiological constraints imposed by the
      time required to encode visual information, complete some amount of lexical
      processing, and then program a saccade. In this article, we review what has been
      learned about these timing constraints from studies using ERP and MEG. On the
      basis of this review, it would appear that the temporal constraints are too
      severe to permit direct lexical control of eye movements without a significant
      amount of parafoveal processing (i.e., pre-processing of word n+1 from word n).
      This conclusion underscores the degree to which the perceptual, cognitive, and
      motor processes involved in reading must be highly coordinated to support skilled
      reading, a par excellence example of a task requiring visual-cognitive expertise.

PMID- 23874282
TI  - Gamma oscillatory amplitude encodes stimulus intensity in primary somatosensory
      cortex.
AB  - Gamma oscillations have previously been linked to pain perception and it has been
      hypothesized that they may have a potential role in encoding pain intensity.
      Stimulus response experiments have reported an increase in activity in the
      primary somatosensory cortex (SI) with increasing stimulus intensity, but the
      specific role of oscillatory dynamics in this change in activation remains
      unclear. In this study, Magnetoencephalography (MEG) was used to investigate the
      changes in cortical oscillations during four different intensities of a train of
      electrical stimuli to the right index finger, ranging from low sensation to
      strong pain. In those participants showing changes in evoked oscillatory gamma in
      SI during stimulation, the strength of the gamma power was found to increase with
      increasing stimulus intensity at both pain and sub-pain thresholds. These results
      suggest that evoked gamma oscillations in SI are not specific to pain but may
      have a role in encoding somatosensory stimulus intensity. 

PMID- 23874283
TI  - Subjective thirst moderates changes in speed of responding associated with water
      consumption.
AB  - Participants (N = 34) undertook a CANTAB battery on two separate occasions after
      fasting and abstaining from fluid intake since the previous evening. On one
      occasion they were offered 500 ml water shortly before testing, and on the other
      occasion no water was consumed prior to testing. Reaction times, as measured by
      Simple Reaction Time (SRT), were faster on the occasion on which they consumed
      water. Furthermore, subjective thirst was found to moderate the effect of water
      consumption on speed of responding. Response latencies in the SRT task were
      greater under the "no water" condition than under the "water" condition, but only
      for those participants with relatively high subjective thirst after abstaining
      from fluid intake overnight. For those participants with relatively low
      subjective thirst, latencies were unaffected by water consumption, and were
      similarly fast as those recorded for thirsty participants who had consumed water.
      These results reveal the novel finding that subjective thirst moderates the
      positive effect of fluid consumption on speed of responding. The results also
      showed evidence that practice also affected task performance. These results imply
      that, for speed of responding at least, the positive effects of water
      supplementation may result from an attenuation of the central processing
      resources consumed by the subjective sensation of thirst that otherwise impair
      the execution of speeded cognitive processes. 

PMID- 23874284
TI  - Emotion and attention interaction: a trade-off between stimuli relevance,
      motivation and individual differences.
AB  - Mounting evidence suggests that the neural processing of emotional stimuli is
      prioritized. However, whether the processing of emotional stimuli is dependent on
      attention remains debatable. Several studies have investigated this issue by
      testing the capacity of emotional distracters to divert processing resources from
      an attentional main task. The attentional load theory postulates that the
      perceptual load of the main task determines the selective processing of the
      distracter. Although we agree with this theory, we also suggest that other
      factors could be important in determining the association between the load of the
      main task and distracter processing, namely, (1) the relevance of the to-be
      ignored stimuli and (2) the engagement in the main task due to motivation. We
      postulate that these factors function as opposite forces to influence distracter
      processing. In addition, we propose that this trade-off is modulated by
      individual differences. In summary, we suggest that the relationship between
      emotion and attention is flexible rather than rigid and depends on several
      factors. Considering this perspective may help us to understand the divergence in
      the results described by several studies in this field. 

PMID- 23874285
TI  - Task-related modulation of effective connectivity during perceptual decision
      making: dissociation between dorsal and ventral prefrontal cortex.
AB  - The dorsal and ventral parts of the lateral prefrontal cortex have been thought
      to play distinct roles in decision making. Although its dorsal part such as the
      frontal eye field (FEF) is shown to play roles in accumulation of sensory
      information during perceptual decision making, the role of the ventral prefrontal
      cortex (PFv) is not well-documented. Previous studies have suggested that the PFv
      is involved in selective attention to the task-relevant information and is
      associated with accuracy of the behavioral performance. It is unknown, however,
      whether the accumulation and selection processes are anatomically dissociated
      between the FEF and PFv. Here we show that, by using concurrent TMS and EEG
      recording, the short-latency (20-40 ms) TMS-evoked potentials after stimulation
      of the FEF change as a function of the time to behavioral response, whereas those
      after stimulation of the PFv change depending on whether the response is correct
      or not. The potentials after stimulation of either region did not show
      significant interaction between time to response and performance accuracy,
      suggesting dissociation between the processes subserved by the FEF and PFv
      networks. The results are consistent with the idea that the network involving the
      FEF plays a role in information accumulation, whereas the network involving the
      PFv plays a role in selecting task relevant information. In addition, stimulation
      of the FEF and PFv induced activation in common regions in the dorsolateral and
      medial frontal cortices, suggesting convergence of information processed in the
      two regions. Taken together, the results suggest dissociation between the FEF and
      PFv networks for their computational roles in perceptual decision making. The
      study also highlights the advantage of TMS-EEG technique in investigating the
      computational processes subserved by the neural network in the human brain with a
      high temporal resolution. 

PMID- 23874286
TI  - The influence of visuospatial attention on unattended auditory 40 Hz responses.
AB  - Information must integrate from multiple brain areas in healthy cognition and
      perception. The present study examined the extent to which cortical responses
      within one sensory modality are modulated by a complex task conducted within
      another sensory modality. Electroencephalographic (EEG) responses were measured
      to a 40 Hz auditory stimulus while individuals attended to modulations in the
      amplitude of the 40 Hz stimulus, and as a function of the difficulty of the
      popular computer game Tetris. The steady-state response to the 40 Hz stimulus was
      isolated by Fourier analysis of the EEG. The response at the stimulus frequency
      was normalized by the response within the surrounding frequencies, generating the
      signal-to-noise ratio (SNR). Seven out of eight individuals demonstrate a
      monotonic increase in the log SNR of the 40 Hz responses going from the difficult
      visuospatial task to the easy visuospatial task to attending to the auditory
      stimuli. This pattern is represented statistically by a One-Way ANOVA, indicating
      significant differences in log SNR across the three tasks. The sensitivity of 40
      Hz auditory responses to the visuospatial load was further demonstrated by a
      significant correlation between log SNR and the difficulty (i.e., speed) of the
      Tetris task. Thus, the results demonstrate that 40 Hz auditory cortical responses
      are influenced by an individual's goal-directed attention to the stimulus, and by
      the degree of difficulty of a complex visuospatial task. 

PMID- 23874287
TI  - Motor cortical regulation of sparse synergies provides a framework for the
      flexible control of precision walking.
AB  - We have previously described a modular organization of the locomotor step cycle
      in the cat in which a number of sparse synergies are activated sequentially
      during the swing phase of the step cycle (Krouchev et al., 2006). Here, we
      address how these synergies are modified during voluntary gait modifications.
      Data were analysed from 27 bursts of muscle activity (recorded from 18 muscles)
      recorded in the forelimb of the cat during locomotion. These were grouped into 10
      clusters, or synergies, during unobstructed locomotion. Each synergy was
      comprised of only a small number of muscles bursts (sparse synergies), some of
      which included both proximal and distal muscles. Eight (8/10) of these synergies
      were active during the swing phase of locomotion. Synergies observed during the
      gait modifications were very similar to those observed during unobstructed
      locomotion. Constraining these synergies to be identical in both the lead (first
      forelimb to pass over the obstacle) and the trail (second limb) conditions
      allowed us to compare the changes in phase and magnitude of the synergies
      required to modify gait. In the lead condition, changes were observed
      particularly in those synergies responsible for transport of the limb and
      preparation for landing. During the trail condition, changes were particularly
      evident in those synergies responsible for lifting the limb from the ground at
      the onset of the swing phase. These changes in phase and magnitude were adapted
      to the size and shape of the obstacle over which the cat stepped. These results
      demonstrate that by modifying the phase and magnitude of a finite number of
      muscle synergies, each comprised of a small number of simultaneously active
      muscles, descending control signals could produce very specific modifications in
      limb trajectory during locomotion. We discuss the possibility that these changes
      in phase and magnitude could be produced by changes in the activity of neurones
      in the motor cortex. 

PMID- 23874288
TI  - Graph theoretical analysis of resting magnetoencephalographic functional
      connectivity networks.
AB  - Complex networks have been observed to comprise small-world properties, believed
      to represent an optimal organization of local specialization and global
      integration of information processing at reduced wiring cost. Here, we applied
      magnitude squared coherence to resting magnetoencephalographic time series in
      reconstructed source space, acquired from controls and patients with
      schizophrenia, and generated frequency-dependent adjacency matrices modeling
      functional connectivity between virtual channels. After configuring undirected
      binary and weighted graphs, we found that all human networks demonstrated highly
      localized clustering and short characteristic path lengths. The most
      conservatively thresholded networks showed efficient wiring, with topographical
      distance between connected vertices amounting to one-third as observed in
      surrogate randomized topologies. Nodal degrees of the human networks conformed to
      a heavy-tailed exponentially truncated power-law, compatible with the existence
      of hubs, which included theta and alpha bilateral cerebellar tonsil, beta and
      gamma bilateral posterior cingulate, and bilateral thalamus across all
      frequencies. We conclude that all networks showed small-worldness, minimal
      physical connection distance, and skewed degree distributions characteristic of
      physically-embedded networks, and that these calculations derived from graph
      theoretical mathematics did not quantifiably distinguish between subject
      populations, independent of bandwidth. However, post-hoc measurements of edge
      computations at the scale of the individual vertex revealed trends of reduced
      gamma connectivity across the posterior medial parietal cortex in patients, an
      observation consistent with our prior resting activation study that found
      significant reduction of synthetic aperture magnetometry gamma power across
      similar regions. The basis of these small differences remains unclear. 

PMID- 23874289
TI  - Coupling internal cerebellar models enhances online adaptation and supports
      offline consolidation in sensorimotor tasks.
AB  - The cerebellum is thought to mediate sensorimotor adaptation through the
      acquisition of internal models of the body-environment interaction. These
      representations can be of two types, identified as forward and inverse models.
      The first predicts the sensory consequences of actions, while the second provides
      the correct commands to achieve desired state transitions. In this paper, we
      propose a composite architecture consisting of multiple cerebellar internal
      models to account for the adaptation performance of humans during sensorimotor
      learning. The proposed model takes inspiration from the cerebellar microcomplex
      circuit, and employs spiking neurons to process information. We investigate the
      intrinsic properties of the cerebellar circuitry subserving efficient adaptation
      properties, and we assess the complementary contributions of internal
      representations by simulating our model in a procedural adaptation task. Our
      simulation results suggest that the coupling of internal models enhances learning
      performance significantly (compared with independent forward and inverse models),
      and it allows for the reproduction of human adaptation capabilities. Furthermore,
      we provide a computational explanation for the performance improvement observed
      after one night of sleep in a wide range of sensorimotor tasks. We predict that
      internal model coupling is a necessary condition for the offline consolidation of
      procedural memories. 

PMID- 23874290
TI  - Analysis of fractal electrodes for efficient neural stimulation.
AB  - Planar electrodes are increasingly used in therapeutic neural stimulation
      techniques such as functional electrical stimulation, epidural spinal cord
      stimulation (ESCS), and cortical stimulation. Recently, optimized electrode
      geometries have been shown to increase the efficiency of neural stimulation by
      increasing the variation of current density on the electrode surface. In the
      present work, a new family of modified fractal electrode geometries is developed
      to enhance the efficiency of neural stimulation. It is shown that a promising
      approach in increasing the neural activation function is to increase the
      "edginess" of the electrode surface, a concept that is explained and quantified
      by fractal mathematics. Rigorous finite element simulations were performed to
      compute electric potential produced by proposed modified fractal geometries. The
      activation of 256 model axons positioned around the electrodes was then
      quantified, showing that modified fractal geometries required a 22% less input
      power while maintaining the same level of neural activation. Preliminary in vivo
      experiments investigating muscle evoked potentials due to median nerve
      stimulation showed encouraging results, supporting the feasibility of increasing
      neural stimulation efficiency using modified fractal geometries. 

PMID- 23874291
TI  - In vivo Imaging of Sarcoptes scabiei Infestation Using Optical Coherence
      Tomography.
AB  - BACKGROUND: Sarcoptes scabiei can be visualized with different imaging tools.
      Optical coherence tomography (OCT) may have the potential to describe the changes
      in skin morphology due to scabies infestation and visualize the parasite.
      METHODS: Five patients from the Departments of Dermatology, Augsburg, Germany,
      and Roskilde, Denmark, were OCT scanned (VivoSight((r)); Michelson Diagnostics
      Ltd., UK). Mites were identified by epiluminescence and light microscopy to
      confirm the diagnosis. RESULTS: OCT identified S. scabiei mites in all patients
      in vivo. Mites and burrows were visualized, and some detail on burrow content was
      provided. CONCLUSION: OCT can visualize S. scabiei mites in vivo, suggesting that
      it may be used to study the biology of the mites in vivo and provide early
      assessment of scabicide therapy. OCT is able to visualize structures in the skin
      with an 8-MUm resolution. Therefore, this technology could potentially allow
      rapid, non-invasive, in vivo diagnosis and analysis of infestations.

PMID- 23874292
TI  - Chromonychia secondary to chemotherapy.
AB  - Chemotherapy drugs can affect the skin and its appendages. Several clinical
      presentations can be observed, depending on the affected structure. The most
      common dermatological side effect is chromonychia. The main causative agents are:
      (1) cyclophosphamide, which can provoke a diffuse, black pigmentation,
      longitudinal striae and dark grey pigmentation located proximally on the nails;
      (2) doxorubicin, which promotes dark brown bands alternating with white striae
      and dark brown pigmentation in transverse bands, and (3) hydroxyurea, which
      produces a distal, diffuse, dark brown pigmentation. In the majority of cases,
      the effects are reversible after the suspension of the causative agent for a few
      months. We report a patient who developed chromonychia while undergoing treatment
      with cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and
      cytarabine for acute lymphocytic leukemia. 

PMID- 23874294
TI  - Lichenoid Drug Eruption following Intravenous Application of Orally Formulated
      Diamorphine, a Semisynthetic Heroin.
AB  - BACKGROUND: Lichen planus is a common skin disorder of unknown etiology. Most
      cases are idiopathic, but substances such as gold, antimalarials, penicillamine,
      thiazide diuretics, beta-blockers, arsenic and nonsteroidal anti-inflammatory
      drugs have been implicated as trigger factors. CASE PRESENTATION: We report the
      case of a lichenoid eruption in a male drug addict who administered oral heroin
      (diamorphine) intravenously. Diamorphine was stopped immediately. Following
      topical steroids, phototherapy and oral acitretin, the lesions gradually
      disappeared. A lymphocyte transformation test was negative for pure morphine and
      codeine. DISCUSSION: A coincidental association between the intravenous
      application of orally formulated semisynthetic heroin and the lichenoid eruption
      cannot be completely ruled out. However, the diagnosis of a lichenoid drug
      eruption is favoured over idiopathic lichen planus because of the clear
      chronological correlation between drug use and appearance as well as drug
      withdrawal and disappearance of the skin lesions, and because of a flare-up
      following repeated intravenous application of diamorphine.

PMID- 23874295
TI  - A Case of Foreign-Body Granuloma of the Glabella due to Polyacrylamide Filler and
      an Intractable Ulcer after Skin Biopsy: An Immunohistochemical Evaluation of
      Inflammatory Changes.
AB  - INTRODUCTION: Polyacrylamide hydrogel has been considered a safe and
      biocompatible soft tissue filler, and it has been widely used in cosmetic
      procedures. However, recent studies have revealed some complications with
      polyacrylamide filler injections. CASE REPORT: We present the case of foreign
      body granulomas of the glabella, which subsequently formed an infectious ulcer 3
      years after a polyacrylamide injection. An immunohistochemical evaluation of the
      foreign-body granulomas was performed in order to study the relationship between
      foreign-body granulomas and immune response. CONCLUSION: We believe that our
      analysis of foreign-body granulomas 1 and 3 years after a filler injection may
      contribute to revealing the mechanism of chronic and intractable infections after
      filler injections.

PMID- 23874293
TI  - Scleromyxedema: a case report and review of the literature.
AB  - Scleromyxedema (SM) is a sclerotic variant of lichen or papular mucinosis in
      which lichenoid papules and scleroderma-like features are both present. It is a
      rare deposition disorder characterized by generalized papular and sclerodermoid
      eruptions, mucin deposition, increased fibroblast proliferation, fibrosis, and
      monoclonal gammopathy (also known as paraproteinemia) mainly of the
      immunoglobulin G-lambda type in the absence of thyroid disease. It usually
      affects middle-aged adults and shows no gender or racial predilection. In
      addition to the skin findings and paraproteinemia, patients with SM have variable
      multisystem affections that mimic systemic sclerosis; the systems which are
      commonly involved include the gastrointestinal tract, musculoskeletal, pulmonary,
      cardiovascular, renal, and central nervous systems, leading to significant
      morbidity and mortality. Prominent symptoms include dysphagia, proximal muscle
      weakness, and dyspnea on exertion; less common but important findings include
      central nervous system involvement in the form of encephalopathy, convulsions,
      coma, and psychosis. 

PMID- 23874296
TI  - Lateral and dorsal column hyperintensity on magnetic resonance imaging in a
      patient with myelopathy associated with intrathecal chemotherapy.
AB  - Chemotherapy-related myelopathy mimicking subacute combined degeneration (SCD)
      has rarely been reported. We encountered a 35-year-old female with sensory ataxia
      after intrathecal chemotherapy. Spinal magnetic resonance imaging showed
      localized abnormal signal areas in the lateral and dorsal white matter, mimicking
      SCD. Diffusion imaging showed restricted water diffusion and increased
      microstructural complexity, and cerebrospinal fluid analysis showed increased
      levels of myelin basic proteins, indicating demyelinating myelopathy. Advanced
      diffusion imaging can provide more information on the microstructure of
      chemotherapy-related myelopathy. 

PMID- 23874298
TI  - VBM with viscous fluid registration of gray matter segments in SPM.
AB  - Improved registration of gray matter segments in SPM has been achieved with the
      DARTEL algorithm. Previous work from our group suggested, however, that such
      improvements may not translate to studies of clinical groups. To address the
      registration issue in atrophic brains, this paper relaxed the condition of
      diffeomorphism, central to DARTEL, and made use of a viscous fluid registration
      model with limited regularization constraints to register the modulated gray
      matter probability maps to an intra-population template. Quantitative analysis of
      the registration results after the additional viscous fluid step showed no
      worsening of co-localization of fiducials compared to DARTEL or unified
      segmentation methods, and the resulting voxel based morphometry (VBM) analyses
      were able to better identify atrophic regions and to produce results with fewer
      apparent false positives. DARTEL showed great sensitivity to atrophy, but the
      resulting VBM maps presented broad, amorphous regions of significance that are
      hard to interpret. We propose that the condition of diffeomorphism is not
      necessary for basic VBM studies in atrophic populations, but also that it has
      disadvantages that must be taken into consideration before a study. The presented
      viscous fluid registration method is proposed for VBM studies to enhance
      sensitivity and localizing power. 

PMID- 23874297
TI  - Brain injury, neuroinflammation and Alzheimer's disease.
AB  - With as many as 300,000 United States troops in Iraq and Afghanistan having
      suffered head injuries (Miller, 2012), traumatic brain injury (TBI) has garnered
      much recent attention. While the cause and severity of these injuries is
      variable, severe cases can lead to lifelong disability or even death. While aging
      is the greatest risk factor for Alzheimer's disease (AD), it is now becoming
      clear that a history of TBI predisposes the individual to AD later in life
      (Sivanandam and Thakur, 2012). In this review article, we begin by defining
      hallmark pathological features of AD and the various forms of TBI. Putative
      mechanisms underlying the risk relationship between these two neurological
      disorders are then critically considered. Such mechanisms include precipitation
      and 'spreading' of cerebral amyloid pathology and the role of neuroinflammation.
      The combined problems of TBI and AD represent significant burdens to public
      health. A thorough, mechanistic understanding of the precise relationship between
      TBI and AD is of utmost importance in order to illuminate new therapeutic
      targets. Mechanistic investigations and the development of preclinical
      therapeutics are reliant upon a clearer understanding of these human diseases and
      accurate modeling of pathological hallmarks in animal systems. 

PMID- 23874299
TI  - A review of cardiorespiratory fitness-related neuroplasticity in the aging brain.
AB  - The literature examining the relationship between cardiorespiratory fitness and
      the brain in older adults has increased rapidly, with 30 of 34 studies published
      since 2008. Here we review cross-sectional and exercise intervention studies in
      older adults examining the relationship between cardiorespiratory fitness and
      brain structure and function, typically assessed using Magnetic Resonance Imaging
      (MRI). Studies of patients with Alzheimer's disease are discussed when available.
      The structural MRI studies revealed a consistent positive relationship between
      cardiorespiratory fitness and brain volume in cortical regions including anterior
      cingulate, lateral prefrontal, and lateral parietal cortex. Support for a
      positive relationship between cardiorespiratory fitness and medial temporal lobe
      volume was less consistent, although evident when a region-of-interest approach
      was implemented. In fMRI studies, cardiorespiratory fitness in older adults was
      associated with activation in similar regions as those identified in the
      structural studies, including anterior cingulate, lateral prefrontal, and lateral
      parietal cortex, despite heterogeneity among the functional tasks implemented.
      This comprehensive review highlights the overlap in brain regions showing a
      positive relationship with cardiorespiratory fitness in both structural and
      functional imaging modalities. The findings suggest that aerobic exercise and
      cardiorespiratory fitness contribute to healthy brain aging, although additional
      studies in Alzheimer's disease are needed. 

PMID- 23874301
TI  - Fkh1 and Fkh2 associate with Sir2 to control CLB2 transcription under normal and
      oxidative stress conditions.
AB  - The Forkhead (Fkh) box family of transcription factors is evolutionary conserved
      from yeast to higher eukaryotes and its members are involved in many
      physiological processes including metabolism, DNA repair, cell cycle, stress
      resistance, apoptosis, and aging. In budding yeast, four Fkh transcription
      factors were identified, namely Fkh1, Fkh2, Fhl1, and Hcm1, which are implicated
      in chromatin silencing, cell cycle regulation, and stress response. These factors
      impinge transcriptional regulation during cell cycle progression, and histone
      deacetylases (HDACs) play an essential role in this process, e.g., the nuclear
      localization of Hcm1 depends on Sir2 activity, whereas Sin3/Rpd3 silence cell
      cycle specific gene transcription in G2/M phase. However, a direct involvement of
      Sir2 in Fkh1/Fkh2-dependent regulation of target genes is at present unknown.
      Here, we show that Fkh1 and Fkh2 associate with Sir2 in G1 and M phase, and that
      Fkh1/Fkh2-mediated activation of reporter genes is antagonized by Sir2. We
      further report that Sir2 overexpression strongly affects cell growth in an
      Fkh1/Fkh2-dependent manner. In addition, Sir2 regulates the expression of the
      mitotic cyclin Clb2 through Fkh1/Fkh2-mediated binding to the CLB2 promoter in G1
      and M phase. We finally demonstrate that Sir2 is also enriched at the CLB2
      promoter under stress conditions, and that the nuclear localization of Sir2 is
      dependent on Fkh1 and Fkh2. Taken together, our results show a functional
      interplay between Fkh1/Fkh2 and Sir2 suggesting a novel mechanism of cell cycle
      repression. Thus, in budding yeast, not only the regulation of G2/M gene
      expression but also the protective response against stress could be directly
      coordinated by Fkh1 and Fkh2. 

PMID- 23874302
TI  - The role and regulation of erythropoietin (EPO) and its receptor in skeletal
      muscle: how much do we really know?
AB  - Erythropoietin (EPO) primarily activates erythroid cell proliferation and growth
      and is active in several types of non-hematopoietic cells via its interaction
      with the EPO-receptor (EPO-R). This review focuses on the role of EPO in skeletal
      muscle. The EPO-R is expressed in skeletal muscle cells and EPO may promote
      myoblast differentiation and survival via the activation of the same signaling
      cascades as in hematopoietic cells, such as STAT5, MAPK and Akt. Inconsistent
      results exist with respect to the detection of the EPO-R mRNA and protein in
      muscle cells, tissue and across species and the use of non-specific EPO-R
      antibodies contributes to this problem. Additionally, the inability to
      reproducibly detect an activation of the known EPO-induced signaling pathways in
      skeletal muscle questions the functionality of the EPO-R in muscle in vivo. These
      equivocal findings make it difficult to distinguish between a direct effect of
      EPO on skeletal muscle, via the activation of its receptor, and an indirect
      effect resulting from a better oxygen supply to the muscle. Consequently, the
      precise role of EPO in skeletal muscle and its regulatory mechanism/s remain to
      be elucidated. Further studies are required to comprehensively establish the
      importance of EPO and its function in skeletal muscle health. 

PMID- 23874303
TI  - Tumor cell-macrophage interactions increase angiogenesis through secretion of
      EMMPRIN.
AB  - Tumor macrophages are generally considered to be alternatively/M2 activated to
      induce secretion of pro-angiogenic factors such as VEGF and MMPs. EMMPRIN (CD147,
      basigin) is overexpressed in many tumor types, and has been shown to induce
      fibroblasts and endothelial cell expression of MMPs and VEGF. We first show that
      tumor cell interactions with macrophages resulted in increased expression of
      EMMPRIN and induction of MMP-9 and VEGF. Human A498 renal carcinoma or MCF-7
      breast carcinoma cell lines were co-cultured with the U937 monocytic-like cell
      line in the presence of TNFalpha (1 ng/ml). Membranal EMMPRIN expression was
      increased in the co-cultures (by 3-4-folds, p < 0.01), as was the secretion of
      MMP-9 and VEGF (by 2-5-folds for both MMP-9 and VEGF, p < 0.01), relative to the
      single cultures with TNFalpha. Investigating the regulatory mechanisms, we show
      that EMMPRIN was post-translationally regulated by miR-146a, as no change was
      observed in the tumoral expression of EMMPRIN mRNA during co-culture, expression
      of miR-146a was increased and its neutralization by its antagomir inhibited
      EMMPRIN expression. The secretion of EMMPRIN was also enhanced (by 2-3-folds, p <
      0.05, only in the A498 co-culture) via shedding off of the membranal protein by a
      serine protease that is yet to be identified, as demonstrated by the use of wide
      range protease inhibitors. Finally, soluble EMMPRIN enhanced monocytic secretion
      of MMP-9 and VEGF, as inhibition of its expression levels by neutralizing anti
      EMMPRIN or siRNA in the tumor cells lead to subsequent decreased induction of
      these two pro-angiogenic proteins. These results reveal a mechanism whereby tumor
      cell-macrophage interactions promote angiogenesis via an EMMPRIN-mediated
      pathway. 

PMID- 23874300
TI  - A delicate balance: Iron metabolism and diseases of the brain.
AB  - Iron is the most abundant transition metal within the brain, and is vital for a
      number of cellular processes including neurotransmitter synthesis, myelination of
      neurons, and mitochondrial function. Redox cycling between ferrous and ferric
      iron is utilized in biology for various electron transfer reactions essential to
      life, yet this same chemistry mediates deleterious reactions with oxygen that
      induce oxidative stress. Consequently, there is a precise and tightly controlled
      mechanism to regulate iron in the brain. When iron is dysregulated, both
      conditions of iron overload and iron deficiencies are harmful to the brain. This
      review focuses on how iron metabolism is maintained in the brain, and how an
      alteration to iron and iron metabolism adversely affects neurological function. 

PMID- 23874305
TI  - Putative interaction of brush cells with bicarbonate secreting cells in the
      proximal corpus mucosa.
AB  - The gastric epithelium is protected from the highly acidic luminal content by
      alkaline mucus which is secreted from specialized epithelial cells. In the
      stomach of mice strong secretion of alkaline fluid was observed at the "gastric
      groove," the border between corpus and fundus mucosa. Since this region is
      characterized by numerous brush cells it was proposed that these cells might
      secrete alkaline solution as suggested for brush cells in the bile duct. In fact,
      it was found that in this region multiple cells express elements which are
      relevant for the secretion of bicarbonate, including carbonic anhydrase (CAII),
      the cystic fibrosis transmembrane conductance regulator (CFTR) and the Na(+)/H(+)
      exchanger (NHE1). However, this cell population was distinct from brush cells
      which express the TRP-channel TRPM5 and are considered as putative sensory cells.
      The location of both cell populations in close proximity implies the possibility
      for a paracrine interaction. This view was substantiated by the finding that
      brush cells express prostaglandin synthase-1 (COX-1) and the neighboring cells a
      specific receptor type for prostaglandins. The notion that brush cells may be
      able to sense a local acidification was supported by the observation that they
      express the channel PKD1L3 which contributes to the acid responsiveness of
      gustatory sensory cells. The results support the concept that brush cells may
      sense the luminal content and influence via prostaglandins the secretion of
      alkaline solution. 

PMID- 23874304
TI  - The genetic component of Brugada syndrome.
AB  - Brugada syndrome (BrS) is a clinical entity first described in 1992. BrS is
      characterized by ST-segment elevations in the right precordial leads and
      susceptibility to ventricular arrhythmias and sudden cardiac death. It affects
      young subjects, predominantly males, with structurally normal hearts. The
      prevalence varies with ethnicity ranging from 1:2,000 to 1:100,000 in different
      parts of the world. Today, hundreds of variants in 17 genes have been associated
      with BrS of which mutations in SCN5A, coding for the cardiac voltage-gated sodium
      channel, accounts for the vast majority. Despite this, approximately 70% of BrS
      cases cannot be explained genetically with the current knowledge. Moreover, the
      monogenic role of some of the variants previously described as being associated
      with BrS has been questioned by their occurrence in about 4% (1:23) of the
      general population as found in NHLBI GO Exome Sequencing Project (ESP) currently
      including approximately 6500 individuals. If we add the variants described in the
      five newest identified genes associated with BrS, they appear at an even higher
      prevalence in the ESP (1:21). The current standard treatment of BrS is an
      implantable cardioverter-defibrillator (ICD). The risk stratification and
      indications for ICD treatment are based on the ECG and on the clinical and family
      history. In this review we discuss the genetic basis of BrS. 

PMID- 23874306
TI  - How Much Child Sexual Abuse is "Below the Surface," and Can We Help Adults
      Identify it Early?
AB  - Child sexual abuse (CSA) occurs frequently in society to children aged between 2
      and 17. It is significantly more common in girls than boys, with the peak age for
      CSA occurring when girls are aged 13-17. Many children experience multiple
      episodes of CSA, as well as having high rates of other victimizations (such as
      physical assaults). One of the problems for current research in CSA is different
      definitions of what this means, and no recent review has clearly differentiated
      more severe forms of CSA, and how commonly this is disclosed. In general we
      suggest there are four types of behavior that should be included as CSA, namely
      (1) non-contact, (2) genital touching, (3) attempted vaginal and anal penetrative
      acts, and (4) vaginal and anal penetrative acts. Evidence suggests that CSA
      involving types (2), (3), and (4) is more likely to have significant long-term
      outcomes, and thus can be considered has having higher-impact. From the research
      to date approximately 15% of girls aged 2-17 experience higher-impact CSA (with
      most studies suggesting that between 12 and 18% of girls experience higher-impact
      CSA). Approximately 6% of boys experience higher-impact CSA (with most studies
      suggesting that between 5 and 8% experience higher-impact CSA). The data also
      suggests that in over 95% of cases the CSA is never disclosed to authorities.
      Thus, CSA is frequent but often not identified, and occurs "below the surface" in
      the vast majority of higher-impact cases. Helping adults to understand "below the
      surface" CSA might help them to recognize it early, but there are very few
      indicators specific to CSA, making this a challenging goal to achieve.
      Nonetheless, given that CSA frequently occurs with other types of abuse, a
      training program that focuses on both CSA and other abuse may offer a method to
      allow both early recognition and prevention by adults in the general population. 

PMID- 23874307
TI  - Neural circuitry of impulsivity in a cigarette craving paradigm.
AB  - Impulsivity has been shown to play a pivotal role in the onset, pattern of
      consumption, relapse and, most notably, craving of illicit and licit drugs such
      as cigarette smoking. The goal of this study was to examine the neurobiological
      influence of trait impulsivity during cue-induced cigarette craving. Thirty-one
      chronic smokers passively viewed appetitive smoking-related and neutral images
      while being scanned and reported their feelings of craving. They completed the
      Barratt Impulsiveness Scale, a measure of trait impulsivity. We conducted
      functional connectivity analyses using the psycho-physiological interaction
      method. During the processing of smoking stimuli, participants presented
      increased activations in the cingulate and prefrontal cortices. We observed a
      significant positive relationship between impulsivity scores and reported
      craving. A negative correlation was observed between the impulsivity score and
      activity in the posterior cingulate cortex (PCC). The insula, dorsal anterior
      cingulate cortex (dACC) as well as the dorsolateral prefrontal cortex (DLPFC)
      presented a negative connectivity with the PCC. Consistent with the view that the
      PCC is related to the ability to resist cigarette craving, our results suggest
      that high impulsive smokers have greater difficulty in controlling their
      cravings, and that this weakness may be mediated by lower PCC activity. Moreover,
      we argue that the less PCC activity, the greater the probability of a stronger
      emotional, physiological, and biased attentional response to smoking cues
      mediated by insula, dACC, and DLPFC activity. This is the first study on this
      topic, and so, results will need to be replicated in both licit and illicit drug
      abusers. Our findings also highlight a need for more emphasis on the PCC in drug
      addiction research, as it is one of the most consistently activated regions in
      functional magnetic resonance imaging studies examining the neural correlates of
      cue-induced alcohol, drug, and tobacco cravings. 

PMID- 23874308
TI  - Domain-specific perceptual causality in children depends on the spatio-temporal
      configuration, not motion onset.
AB  - Humans, even babies, perceive causality when one shape moves briefly and linearly
      after another. Motion timing is crucial in this and causal impressions disappear
      with short delays between motions. However, the role of temporal information is
      more complex: it is both a cue to causality and a factor that constrains
      processing. It affects ability to distinguish causality from non-causality, and
      social from mechanical causality. Here we study both issues with 3- to 7-year
      olds and adults who saw two computer-animated squares and chose if a picture of
      mechanical, social or non-causality fit each event best. Prior work fit with the
      standard view that early in development, the distinction between the social and
      physical domains depends mainly on whether or not the agents make contact, and
      that this reflects concern with domain-specific motion onset, in particular,
      whether the motion is self-initiated or not. The present experiments challenge
      both parts of this position. In Experiments 1 and 2, we showed that not just
      spatial, but also animacy and temporal information affect how children
      distinguish between physical and social causality. In Experiments 3 and 4 we
      showed that children do not seem to use spatio-temporal information in perceptual
      causality to make inferences about self- or other-initiated motion onset.
      Overall, spatial contact may be developmentally primary in domain-specific
      perceptual causality in that it is processed easily and is dominant over
      competing cues, but it is not the only cue used early on and it is not used to
      infer motion onset. Instead, domain-specific causal impressions may be automatic
      reactions to specific perceptual configurations, with a complex role for temporal
      information. 

PMID- 23874310
TI  - How to measure wisdom: content, reliability, and validity of five measures.
AB  - Wisdom is a field of growing interest both inside and outside academic
      psychology, and researchers are increasingly interested in using measures of
      wisdom in their work. However, wisdom is a highly complex construct, and its
      various operationalizations are based on quite different definitions. Which
      measure a researcher chooses for a particular research project may have a strong
      influence on the results. This study compares four well-established measures of
      wisdom-the Self-Assessed Wisdom Scale (Webster, 2003, 2007), the Three
      Dimensional Wisdom Scale (Ardelt, 2003), the Adult Self-Transcendence Inventory
      (Levenson et al., 2005), and the Berlin Wisdom Paradigm (Baltes and Smith, 1990;
      Baltes and Staudinger, 2000)-with respect to content, reliability, factorial
      structure, and construct validity (relationships to wisdom nomination, interview
      based wisdom ratings, and correlates of wisdom). The sample consisted of 47
      wisdom nominees and 123 control participants. While none of the measures
      performed "better" than the others by absolute standards, recommendations are
      given for researchers to select the most suitable measure for their substantive
      interests. In addition, a "Brief Wisdom Screening Scale" is introduced that
      contains those 20 items from the three self-report scales that were most highly
      correlated with the common factor across the scales. 

PMID- 23874309
TI  - Speech through ears and eyes: interfacing the senses with the supramodal brain.
AB  - The comprehension of auditory-visual (AV) speech integration has greatly
      benefited from recent advances in neurosciences and multisensory research. AV
      speech integration raises numerous questions relevant to the computational rules
      needed for binding information (within and across sensory modalities), the
      representational format in which speech information is encoded in the brain
      (e.g., auditory vs. articulatory), or how AV speech ultimately interfaces with
      the linguistic system. The following non-exhaustive review provides a set of
      empirical findings and theoretical questions that have fed the original proposal
      for predictive coding in AV speech processing. More recently, predictive coding
      has pervaded many fields of inquiries and positively reinforced the need to
      refine the notion of internal models in the brain together with their
      implications for the interpretation of neural activity recorded with various
      neuroimaging techniques. However, it is argued here that the strength of
      predictive coding frameworks reside in the specificity of the generative internal
      models not in their generality; specifically, internal models come with a set of
      rules applied on particular representational formats themselves depending on the
      levels and the network structure at which predictive operations occur. As such,
      predictive coding in AV speech owes to specify the level(s) and the kinds of
      internal predictions that are necessary to account for the perceptual benefits or
      illusions observed in the field. Among those specifications, the actual content
      of a prediction comes first and foremost, followed by the representational
      granularity of that prediction in time. This review specifically presents a
      focused discussion on these issues. 

PMID- 23874311
TI  - Bodies adapt orientation-independent face representations.
AB  - Faces and bodies share a great number of semantic attributes, such as gender,
      emotional expressiveness, and identity. Recent studies demonstrate that bodies
      can activate and modulate face perception. However, the nature of the face
      representation that is activated by bodies remains unknown. In particular, face
      and body representations have previously been shown to have a degree of
      orientation specificity. Here we use body-face adaptation aftereffects to test
      whether bodies activate face representations in an orientation-dependent manner.
      Specifically, we used a two-by-two design to examine the magnitude of the body
      face aftereffect using upright and inverted body adaptors and upright and
      inverted face targets. All four conditions showed significant body-face
      adaptation. We found neither a main effect of body orientation nor an interaction
      between body and face orientation. There was a main effect of target face
      orientation, with inverted target faces showing larger aftereffects than upright
      target faces, consistent with traditional face-face adaptation. Taken together,
      these results suggest that bodies adapt and activate a relatively orientation
      independent representation of faces. 

PMID- 23874312
TI  - Goal Commitments and the content of thoughts and dreams: basic principles.
AB  - A few empirically supported principles can account for much of the thematic
      content of waking thought, including rumination, and dreams. (1) An individual's
      commitments to particular goals sensitize the individual to respond to cues
      associated with those goals. The cues may be external or internal in the person's
      own mental activity. The responses may take the form of noticing the cues,
      storing them in memory, having thoughts or dream segments related to them, and/or
      taking action. Noticing may be conscious or not. Goals may be any desired
      endpoint of a behavioral sequence, including finding out more about something,
      i.e., exploring possible goals, such as job possibilities or personal
      relationships. (2) Such responses are accompanied and perhaps preceded by
      protoemotional activity or full emotional arousal, the amplitude of which
      determines the likelihood of response and is related to the value placed on the
      goal. (3) When the individual is in a situation conducive to making progress
      toward attaining the goal, the response to goal cues takes the form of actions or
      operant mental acts that advance the goal pursuit. (4) When circumstances are
      unfavorable for goal-directed operant behavior, the response remains purely
      mental, as in mind-wandering and dreaming, but still reflects the content of the
      goal pursuit or associated content. (5) Respondent responses such as mind
      wandering are more likely when the individual is mentally unoccupied with ongoing
      tasks and less likely the more that is at stake in the ongoing task. The
      probability of respondent thought is highest during relaxed periods, when the
      brain's default-mode network dominates, or during sleep. The article briefly
      summarizes neurocognitive findings that relate to mind-wandering and evidence
      regarding adverse effects of mind-wandering on task performance as well as
      evidence suggesting adaptive functions in regard to creative problem-solving,
      planning, resisting delay discounting, and memory consolidation. 

PMID- 23874314
TI  - Involvement of the larynx motor area in singing-voice perception: a TMS study(?).
AB  - Recent evidence has reported that the motor system has a role in speech or
      emotional vocalization discrimination. In the present study we investigated the
      involvement of the larynx motor representation in singing perception. Twenty-one
      non-musicians listened to short tones sung by a human voice or played by a
      machine and performed a categorization task. Thereafter continuous theta-burst
      transcranial magnetic stimulation was applied over the right larynx premotor area
      or on the vertex and the test administered again. Overall, reaction times (RTs)
      were shorter after stimulation over both sites. Nonetheless and most importantly,
      RTs became longer for sung than for "machine" sounds after stimulation on the
      larynx area. This effect suggests that the right premotor region is functionally
      involved in singing perception and that sound humanness modulates motor
      resonance. 

PMID- 23874313
TI  - MUC (Memory, Unification, Control) and beyond.
AB  - A neurobiological model of language is discussed that overcomes the shortcomings
      of the classical Wernicke-Lichtheim-Geschwind model. It is based on a subdivision
      of language processing into three components: Memory, Unification, and Control.
      The functional components as well as the neurobiological underpinnings of the
      model are discussed. In addition, the need for extension of the model beyond the
      classical core regions for language is shown. The attention network and the
      network for inferential processing are crucial to realize language comprehension
      beyond single word processing and beyond decoding propositional content. It is
      shown that this requires the dynamic interaction between multiple brain regions. 

PMID- 23874315
TI  - Attention's grasp: early and late hand proximity effects on visual evoked
      potentials.
AB  - Behavioral studies suggest that visual attention is biased toward stimuli in the
      region of space near the palm of the hand, but it is unclear whether this effect
      is universal or selective for goal/task-related stimuli. We examined event
      related potentials (ERPs) using a visual detection task in which the hand was
      placed near or kept far from target and non-target stimuli that were matched for
      frequency and visual features to avoid confounding factors. Focusing on attention
      sensitive ERP components, we found that P3 (350-450 ms) amplitudes were increased
      for Hand Near conditions for targets only, demonstrating a selective effect
      consistent with the P3's cross-modal and task-relevance influences. An N1 variant
      implicated in visuo-tactile integration (central Nd1; 120-190 ms) showed similar
      target-specific effects. P1 (80-110 ms) effects for target stimuli were also
      apparent, but may have applied to non-targets as well, which would be consistent
      with the P1's association with early, pre-categorical increases in sensory gain.
      Collectively, these findings suggest that by the time stimuli are categorized as
      relevant/irrelevant for action, the proprioceptive effects of the hand on visual
      attention are selective for goal/task-related stimuli. At the same time, hand
      proximity appears to bias attention early, starting with a facilitation of
      processing for perhaps any visual stimuli near the hand, and continuing with
      enhancements that are selective to those stimuli categorized as task-relevant. 

PMID- 23874316
TI  - Converging toward a common speech code: imitative and perceptuo-motor
      recalibration processes in speech production.
AB  - Auditory and somatosensory systems play a key role in speech motor control. In
      the act of speaking, segmental speech movements are programmed to reach phonemic
      sensory goals, which in turn are used to estimate actual sensory feedback in
      order to further control production. The adult's tendency to automatically
      imitate a number of acoustic-phonetic characteristics in another speaker's speech
      however suggests that speech production not only relies on the intended phonemic
      sensory goals and actual sensory feedback but also on the processing of external
      speech inputs. These online adaptive changes in speech production, or phonetic
      convergence effects, are thought to facilitate conversational exchange by
      contributing to setting a common perceptuo-motor ground between the speaker and
      the listener. In line with previous studies on phonetic convergence, we here
      demonstrate, in a non-interactive situation of communication, online
      unintentional and voluntary imitative changes in relevant acoustic features of
      acoustic vowel targets (fundamental and first formant frequencies) during speech
      production and imitation. In addition, perceptuo-motor recalibration processes,
      or after-effects, occurred not only after vowel production and imitation but also
      after auditory categorization of the acoustic vowel targets. Altogether, these
      findings demonstrate adaptive plasticity of phonemic sensory-motor goals and
      suggest that, apart from sensory-motor knowledge, speech production continuously
      draws on perceptual learning from the external speech environment. 

PMID- 23874317
TI  - Imagined motor action and eye movements in schizophrenia.
AB  - Visual exploration and planning of actions are reported to be abnormal in
      schizophrenia. Most of the studies monitoring eye movements in patients with
      schizophrenia have been performed under free-viewing condition. The present study
      was designed to assess whether mentally performing an action modulates the
      visuomotor behavior in patients with schizophrenia and in healthy controls.
      Visual scan paths were monitored in eighteen patients with schizophrenia and in
      eighteen healthy controls. Participants performed two tasks in which they were
      asked either to (1) look at a scene on a computer screen (free viewing), or (2)
      picture themselves making a sandwich in front of a computer screen (active
      viewing). The scenes contained both task-relevant and task-irrelevant objects.
      Temporal and spatial characteristics of scan paths were compared for each group
      and each task. The results indicate that patients with schizophrenia exhibited
      longer fixation durations, and fewer fixations, than healthy controls in the free
      viewing condition. The patients' visual exploration improved in the active
      viewing condition. However, patients looked less at task-relevant objects and
      looked more at distractors than controls in the active viewing condition in which
      they were asked to picture themselves making a sandwich in moving their eyes to
      task-relevant objects on an image. These results are consistent with the
      literature on deficits in motor imagery in patients with schizophrenia and it
      extends the impairment to visual exploration in an action imagery task. 

PMID- 23874318
TI  - Feature tracking and aging.
AB  - There are conflicting results regarding the effect of aging on second-order
      motion processing (i.e., motion defined by attributes other than luminance, such
      as contrast). Two studies (Habak and Faubert, 2000; Tang and Zhou, 2009) found
      that second-order motion processing was more vulnerable to aging than first-order
      motion processing. Conversely, Billino et al. (2011) recently found that aging
      affected first- and second-order motion processing by similar proportions. These
      three studies used contrast-defined motion as a second-order stimulus, but there
      can be at least two potential issues when using such a stimulus to evaluate age
      related sensitivity losses. First, it has been shown that the motion system
      processing contrast-defined motion varies depending on the stimulus parameters.
      Thus, although all these three studies assumed that their contrast-defined motion
      was processed by a low-level second-order motion system, this was not necessarily
      the case. The second potential issue is that contrast-defined motion consists in
      a contrast modulation of a texture rich in high spatial frequencies and aging
      mainly affects contrast sensitivity at high spatial frequencies. Consequently,
      some age-related sensitivity loss to second-order motion could be due to a lower
      sensitivity to the texture rather than to motion processing per se. To avoid
      these two potential issues, we used a second-order motion stimulus void of high
      spatial frequencies and which has been shown to be processed by a high-level
      feature tracking motion system, namely fractal rotation (Lagace-Nadon et al.,
      2009). We found an age-related deficit on second-order motion processing at all
      temporal frequencies including the ones for which no age-related effect on first
      order motion processing was observed. We conclude that aging affects the ability
      to track features. Previous age-related results on second-order and global motion
      processing are discussed in light of these findings. 

PMID- 23874319
TI  - Is there a generalized magnitude system in the brain? Behavioral, neuroimaging,
      and computational evidence.

PMID- 23874320
TI  - Examining the role of memory in social cognition.

PMID- 23874321
TI  - The siren song of vocal fundamental frequency for romantic relationships.
AB  - A multitude of factors contribute to why and how romantic relationships are
      formed as well as whether they ultimately succeed or fail. Drawing on
      evolutionary models of attraction and speech production as well as integrative
      models of relationship functioning, this review argues that paralinguistic cues
      (more specifically the fundamental frequency of the voice) that are initially a
      strong source of attraction also increase couples' risk for relationship failure.
      Conceptual similarities and differences between the multiple operationalizations
      and interpretations of vocal fundamental frequency are discussed and guidelines
      are presented for understanding both convergent and non-convergent findings.
      Implications for clinical practice and future research are discussed. 

PMID- 23874322
TI  - Utility of TMS to understand the neurobiology of speech.
AB  - According to a traditional view, speech perception and production are processed
      largely separately in sensory and motor brain areas. Recent psycholinguistic and
      neuroimaging studies provide novel evidence that the sensory and motor systems
      dynamically interact in speech processing, by demonstrating that speech
      perception and imitation share regional brain activations. However, the exact
      nature and mechanisms of these sensorimotor interactions are not completely
      understood yet. Transcranial magnetic stimulation (TMS) has often been used in
      the cognitive neurosciences, including speech research, as a complementary
      technique to behavioral and neuroimaging studies. Here we provide an up-to-date
      review focusing on TMS studies that explored speech perception and imitation.
      Single-pulse TMS of the primary motor cortex (M1) demonstrated a speech specific
      and somatotopically specific increase of excitability of the M1 lip area during
      speech perception (listening to speech or lip reading). A paired-coil TMS
      approach showed increases in effective connectivity from brain regions that are
      involved in speech processing to the M1 lip area when listening to speech. TMS in
      virtual lesion mode applied to speech processing areas modulated performance of
      phonological recognition and imitation of perceived speech. In summary, TMS is an
      innovative tool to investigate processing of speech perception and imitation. TMS
      studies have provided strong evidence that the sensory system is critically
      involved in mapping sensory input onto motor output and that the motor system
      plays an important role in speech perception. 

PMID- 23874323
TI  - Gender Identity and Gender Role in DSD Patients Raised as Females: A Preliminary
      Outcome Study.
AB  - Gender identity and gender role are expected to be consistent with gender
      assignment for optimal DSD management outcome. To our knowledge, our study is the
      first to attempt evaluation of gender related outcomes in Turkish DSD patients.
      After receiving institutional ethical board approval and subject (or parent)
      informed consent, subjects with DSD raised as girls (22 patients 46 XX DSD, 11
      patients 46 XY DSD) answered 566 questions of the Minnesota Multiphasic
      Personality Inventory (MMPI) questionnaire including 60-item Masculinity
      Femininity (MF) subscale which was the focus in this study. Controls (n: 50) were
      females similar to the probands in age, level of education, relationship status,
      and having a job or not also answered all questions. The answers were evaluated
      by a trained psychologist (Derya Inceoglu) on MMPI. For statistical purposes,
      seven findings were obtained from the data related to the MF subscale from the
      patients and controls. Of these seven findings (S1-S7), two were associated with
      masculinity (S3-S4) and another two were associated with femininity (S5-S6). In
      DSD patients, the percentages of masculinity findings were significantly higher
      when compared to controls (p < 0.001 and p < 0.001 for S3 and S4, respectively).
      In controls, the percentages of femininity findings were significantly higher
      when compared to DSD females (p < 0.001 and p < 0.001 for S5 and S6
      respectively). There was no significant difference between 46 XX DSD patients and
      46 XY DSD patients with respect to the percentage of any of the seven findings.
      Two patients requested gender change to male; only these two patients had the
      finding stating that sexual impulses could come to existence as actions (S7). In
      conclusion efforts to identify modifiable factors with negative impact and thus
      modifying them, and professional guidance may be important in minimizing the
      encountered gender related problems in DSD patients. 

PMID- 23874324
TI  - SULT2A1 Gene Copy Number Variation is Associated with Urinary Excretion Rate of
      Steroid Sulfates.
AB  - Human cytosolic sulfotransferases (SULT) 2A1 is the main enzyme involved in the
      sulfate conjugation of dehydroepiandrosterone, a weak androgen, and the main
      androgen precursor, whereas estrogens are mainly conjugated by SULT1A1. Here we
      have identified a copy number variation (CNV) polymorphism in the SULT2A1 gene in
      a Swedish population including healthy men (N = 30). Moreover, the CNV of SULT1A1
      and SULT2A1 was further characterized in relation to urinary levels of androgen
      sulfate metabolites before and after an intramuscular dose of 500 mg testosterone
      enanthate. Individuals expressing two or more CNVs excrete 80 and 40% higher
      levels of DHEAS (p = 0.02) and androsteroneS (p = 0.01), respectively as compared
      to individuals with one gene copy. The mean area under the urine concentration
      time-curve from time 0 (prior to the administration of 500 mg testosterone) to 15
      days post dose values were 80% higher for DHEAS (p = 0.046) and testosteroneS (p
      = 0.019) in individuals with two and three SULT2A1 gene copies as compared to
      individuals with one gene copy. The SULT1A1 CNV on the other hand did not affect
      the sulfation activity toward the androgens. In conclusion our results indicate
      that functional CNV polymorphisms in SULT2A1 and SULT1A1 are common in a Swedish
      population and that SULT2A1 CNV is associated with the urinary concentrations of
      androgen sulfate metabolites. 

PMID- 23874325
TI  - Molecular characterization of bla ESBL-harboring conjugative plasmids identified
      in multi-drug resistant Escherichia coli isolated from food-producing animals and
      healthy humans.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-encoding genes are frequently
      mapped to plasmids, yet few of these structures have been characterized at the
      molecular level, to date. METHODS: Eighty-seven ESBL-producing Escherichia coli
      were isolated from fecal samples of food-producing animals and healthy humans in
      Switzerland from 2009 to 2011. Plasmid DNA of all isolates was purified. Broth
      mating assays were carried out individually for 32 isolates to determine if the
      ESBL marker could be transferred by conjugation. The plasmid sizes were
      determined by S1-nuclease pulsed-field gel electrophoresis (PFGE) and the
      plasmids were typed by PCR-based replicon typing. Susceptibility tests by disk
      diffusion followed with a re-analysis S1-nuclease PFGE and PCRs were performed to
      confirm plasmid transfer. Microarray was performed to detect additional
      antibiotic resistance markers and multi-locus sequence typing was also performed
      in selected donor strains. The phylotypes were identified by triplex PCR.
      RESULTS: About half (n = 46) of the 87 isolates carried small (<20-kb) plasmids.
      All selected 32 isolates contained large plasmids (ranging in sizes from 20- to
      600-kb). Eleven plasmid replicon types were detected. Of these, IncFIA (n = 5),
      IncFIB (n = 9), and IncK/B (n = 4) were common. Nine isolates demonstrated the
      ability to transfer their cefotaxime resistance marker at high transfer rates.
      Plasmid profile re-analysis of these transconjugants identified 16 plasmids.
      IncFIB and IncI1 were the most prevalent replicon types. Phylogenetic grouping
      showed that five of the nine donor strains belonged to phylogroup B1. Nine
      different sequence types were identified in nine tested donor strains.
      CONCLUSION: Characterization of these ESBL-encoding conjugative plasmids extends
      our understanding on these resistance markers in multi-drug resistant E. coli
      cultured from healthy human and animal sources.

PMID- 23874326
TI  - Microbial activity in the marine deep biosphere: progress and prospects.
AB  - The vast marine deep biosphere consists of microbial habitats within sediment,
      pore waters, upper basaltic crust and the fluids that circulate throughout it. A
      wide range of temperature, pressure, pH, and electron donor and acceptor
      conditions exists-all of which can combine to affect carbon and nutrient cycling
      and result in gradients on spatial scales ranging from millimeters to kilometers.
      Diverse and mostly uncharacterized microorganisms live in these habitats, and
      potentially play a role in mediating global scale biogeochemical processes.
      Quantifying the rates at which microbial activity in the subsurface occurs is a
      challenging endeavor, yet developing an understanding of these rates is essential
      to determine the impact of subsurface life on Earth's global biogeochemical
      cycles, and for understanding how microorganisms in these "extreme" environments
      survive (or even thrive). Here, we synthesize recent advances and discoveries
      pertaining to microbial activity in the marine deep subsurface, and we highlight
      topics about which there is still little understanding and suggest potential
      paths forward to address them. This publication is the result of a workshop held
      in August 2012 by the NSF-funded Center for Dark Energy Biosphere Investigations
      (C-DEBI) "theme team" on microbial activity (www.darkenergybiosphere.org). 

PMID- 23874327
TI  - Do antibiotic residues in soils play a role in amplification and transmission of
      antibiotic resistant bacteria in cattle populations?
AB  - When we consider factors that contribute to the emergence, amplification, and
      persistence of antibiotic resistant bacteria, the conventional assumption is that
      antibiotic use is the primary driver in these processes and that selection occurs
      primarily in the patient or animal. Evidence suggests that this may not always be
      the case. Experimental trials show that parenteral administration of a third
      generation cephalosporin (ceftiofur) in cattle has limited or short-term effects
      on the prevalence of ceftiofur-resistant bacteria in the gastrointestinal tract.
      While this response may be sufficient to explain a pattern of widespread
      resistance to cephalosporins, approximately two-thirds of ceftiofur metabolites
      are excreted in the urine raising the possibility that environmental selection
      plays an important additive role in the amplification and maintenance of
      antibiotic resistant E. coli on farms. Consequently, we present a rationale for
      an environmental selection hypothesis whereby excreted antibiotic residues such
      as ceftiofur are a significant contributor to the proliferation of antibiotic
      resistant bacteria in food animal systems. We also present a mathematical model
      of our hypothesized system as a guide for designing experiments to test this
      hypothesis. If supported for antibiotics such as ceftiofur, then there may be new
      approaches to combat the proliferation of antibiotic resistance beyond the
      prudent use mantra. 

PMID- 23874329
TI  - Antimicrobial compounds from natural sources.

PMID- 23874330
TI  - Retroviruses, retroelements and their restrictions.

PMID- 23874328
TI  - Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily
      regulated by the two-component system ArcBA through antagonizing the H-NS
      mediated repression.
AB  - The gadE-mdtEF operon encodes a central acid resistance regulator GadE and two
      multidrug efflux proteins MdtEF. Although transcriptional regulation of gadE in
      the context of acid resistance under the aerobic growth environment of
      Escherichia coli has been extensively studied, regulation of the operon under the
      physiologically relevant environment of anaerobic growth and its effect on the
      expression of the multidrug efflux proteins MdtEF in the operon has not been
      disclosed. Our previous study revealed that anaerobic induction of the operon was
      dependent on ArcA, the response regulator of the ArcBA two-component system, in
      the M9 glucose minimal medium. However, the detailed regulatory mechanism remains
      unknown. In this study, we showed that anaerobic activation of mdtEF was driven
      by the 798 bp unusually long gadE promoter. Deletion of evgA, ydeO, rpoS, and
      gadX which has been shown to activate the gadE expression during acid stresses
      under aerobic condition did not have a significant effect on the anaerobic
      activation of the operon. Rather, anaerobic activation of the operon was largely
      dependent on the global regulator ArcA and a GTPase MnmE. Under aerobic
      condition, transcription of gadE was repressed by the global DNA silencer H-NS in
      M9 minimal medium. Interestingly, under anaerobic condition, while DeltaarcA
      almost completely abolished transcription of gadE-mdtEF, further deletion of hns
      in DeltaarcA mutant restored the transcription of the full-length PgadE-lacZ, and
      P1- and P3-lacZ fusions, suggesting an antagonistic effect of ArcA on the H-NS
      mediated repression. Taken together, we conclude that the anaerobic activation of
      the gadE-mdtEF was primarily mediated by the two-component system ArcBA through
      antagonizing the H-NS mediated repression. 

PMID- 23874331
TI  - Prevalence and characteristics of rmtB and qepA in Escherichia coli isolated from
      diseased animals in China.
AB  - 16S rRNA methylase and QepA, a fluoroquinolone efflux pump, are new mechanisms of
      resistance against aminoglycosides and fluoroquinolone, respectively. One of 16S
      rRNA methylase genes, rmtB, was found to be associated with qepA, were both
      located on the same transposable element. In this study, we intended to determine
      the current prevalence and characteristics of the 16S rRNA methylase genes and
      qepA, and to study the association between rmtB and qepA. A total of 892
      Escherichia coli isolates were collected from various diseased food-producing
      animals in China from 2004 to 2008 and screened by PCR for 16S rRNA methylase
      genes and qepA. About 12.6% (112/892) and 0.1% (1/892) of isolates that were
      highly resistant to amikacin were positive for rmtB and armA, respectively. The
      remaining five 16S rRNA methlyase genes were not detected. Thirty-six (4.0%)
      strains carried qepA. About 32.1% of rmtB-positive strains harbored qepA, which
      was not detected in rmtB-negative strains. Most strains were clonally unrelated,
      while identical PFGE profiles of rmtB-positive isolates were found in the same
      farm indicating clonal transmission. Conjugation experiments showed that rmtB was
      transferred to the recipients, and qepA also cotransferred with rmtB in some
      cases. The spread of E. coli of food animal origin harboring both rmtB and qepA
      suggests that surveillance for antimicrobial resistance of animal origin as well
      as the study of the mechanisms of resistance should be undertaken. 

PMID- 23874332
TI  - IL-1 and T Helper Immune Responses.
AB  - CD4 T cells play a critical role in mediating adaptive immunity to a variety of
      pathogens as well as in tumor immunity. If not adequately regulated, CD4 T cells
      can be also involved in autoimmunity, asthma, and allergic responses. During TCR
      activation in a particular cytokine milieu, naive CD4 T cells may differentiate
      into one of several lineages of T helper (Th) cells, including Th1, Th2, and
      Th17, as defined by their pattern of cytokine production and function. IL-1, the
      prototypic proinflammatory cytokine, has been shown to influence growth and
      differentiation of immunocompetent lymphocytes. The differential expression of IL
      1RI on human CD4 T cell subsets confers distinct capacities to acquire specific
      effector functions. In this review, we summarize the role of IL-1 on CD4 T cells,
      in terms of differentiation, activation, and maintenance or survival. 

PMID- 23874333
TI  - Multi-faceted functions of secretory IgA at mucosal surfaces.
AB  - Secretory IgA (SIgA) plays an important role in the protection and homeostatic
      regulation of intestinal, respiratory, and urogenital mucosal epithelia
      separating the outside environment from the inside of the body. This primary
      function of SIgA is referred to as immune exclusion, a process that limits the
      access of numerous microorganisms and mucosal antigens to these thin and
      vulnerable mucosal barriers. SIgA has been shown to be involved in avoiding
      opportunistic pathogens to enter and disseminate in the systemic compartment, as
      well as tightly controlling the necessary symbiotic relationship existing between
      commensals and the host. Clearance by peristalsis appears thus as one of the
      numerous mechanisms whereby SIgA fulfills its function at mucosal surfaces.
      Sampling of antigen-SIgA complexes by microfold (M) cells, intimate contact
      occurring with Peyer's patch dendritic cells (DC), down-regulation of
      inflammatory processes, modulation of epithelial, and DC responsiveness are some
      of the recently identified processes to which the contribution of SIgA has been
      underscored. This review aims at presenting, with emphasis at the biochemical
      level, how the molecular complexity of SIgA can serve these multiple and non
      redundant modes of action. 

PMID- 23874335
TI  - Vitamin-mediated regulation of intestinal immunity.
AB  - The intestine is exposed continuously to complex environments created by numerous
      injurious and beneficial non-self antigens. The unique mucosal immune system in
      the intestine maintains the immunologic homeostasis between the host and the
      external environment. Crosstalk between immunocompetent cells and endogenous
      (e.g., cytokines and chemokines) as well as exogenous factors (e.g., commensal
      bacteria and dietary materials) achieves the vast diversity of intestinal immune
      functions. In addition to their vital roles as nutrients, vitamins now also are
      known to have immunologically crucial functions, specifically in regulating host
      immune responses. In this review, we focus on the immunologic functions of
      vitamins in regulating intestinal immune responses and their roles in moderating
      the fine balance between physiologic and pathologic conditions of the intestine. 

PMID- 23874334
TI  - FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program.
AB  - T cell ontogeny is a sophisticated process, which takes place within the thymus
      through a series of well-defined discrete stages. The process requires a proper
      lympho-stromal interaction. In particular, cortical and medullary thymic
      epithelial cells (cTECs, mTECs) drive T cell differentiation, education, and
      selection processes, while the thymocyte-dependent signals allow thymic
      epithelial cells (TECs) to maturate and provide an appropriate thymic
      microenvironment. Alterations in genes implicated in thymus organogenesis,
      including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1, and Six1, affect this well
      orchestrated process, leading to disruption of thymic architecture. Of note, in
      both human and mice, the primordial TECs are yet unable to fully support T cell
      development and only after the transcriptional activation of the Forkhead-box n1
      (FOXN1) gene in the thymic epithelium this essential function is acquired. FOXN1
      is a master regulator in the TEC lineage specification in that it down-stream
      promotes transcription of genes, which, in turn, regulate TECs differentiation.
      In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC
      homeostasis in the post-natal thymus. An inborn null mutation in FOXN1 leads to
      Nude/severe combined immunodeficiency (SCID) phenotype in mouse, rat, and humans.
      In Foxn1 (-/-) nude animals, initial formation of the primordial organ is
      arrested and the primordium is not colonized by hematopoietic precursors, causing
      a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is
      characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail
      dystrophy, and a severe T cell immunodeficiency, inherited as an autosomal
      recessive disorder. Aim of this review is to summarize all the scientific
      information so far available to better characterize the pivotal role of the
      master regulator FOXN1 transcription factor in the TEC lineage specifications and
      functionality. 

PMID- 23874336
TI  - Natural and induced T regulatory cells in cancer.
AB  - CD4+Foxp3+ T regulatory (Treg) cells control many facets of immune responses
      ranging from autoimmune diseases, to inflammatory conditions, and cancer in an
      attempt to maintain immune homeostasis. Natural Treg (nTreg) cells develop in the
      thymus and constitute a critical arm of active mechanisms of peripheral tolerance
      particularly to self antigens. A growing body of knowledge now supports the
      existence of induced Treg (iTreg) cells which may derive from a population of
      conventional CD4+ T cells. The fork-head transcription factor (Foxp3) typically
      is expressed by natural CD4+ Treg cells, and thus serves as a marker to
      definitively identify these cells. On the contrary, there is less consensus on
      what constitutes iTreg cells as their precise definition has been somewhat
      elusive. This is in part due to their distinct phenotypes which are shaped by
      exposure to certain inflammatory or "assault" signals stemming from the
      underlying immune disorder. The "policing" activity of Treg cells tends to be uni
      directional in several pathological conditions. On one end of the spectrum, Treg
      cell suppressive activity is beneficial by curtailing T cell response against
      self-antigens and allergens thus preventing autoimmune diseases and allergies. On
      the other end however, their inhibitory roles in limiting immune response against
      pseudo-self antigens as in tumors often culminates into negative outcomes. In
      this review, we focus on this latter aspect of Treg cell immunobiology by
      highlighting the involvement of nTreg cells in various animal models and human
      tumors. We further discuss iTreg cells, relationship with their natural
      counterpart, and potential co-operation between the two in modulating immune
      response against tumors. Lastly, we discuss studies focusing on these cells as
      targets for improving anti-tumor immunity. 

PMID- 23874337
TI  - Centrosome polarization in T cells: a task for formins.
AB  - T-cell antigen receptor (TCR) engagement triggers the rapid reorientation of the
      centrosome, which is associated with the secretory machinery, toward the
      immunological synapse (IS) for polarized protein trafficking. Recent evidence
      indicates that upon TCR triggering the INF2 formin, together with the formins
      DIA1 and FMNL1, promotes the formation of a specialized array of stable
      detyrosinated MTs that breaks the symmetrical organization of the T-cell
      microtubule (MT) cytoskeleton. The detyrosinated MT array and TCR-induced
      tyrosine phosphorylation should coincide for centrosome polarization. We propose
      that the pushing forces produced by the detyrosinated MT array, which modify the
      position of the centrosome, in concert with Src kinase dependent TCR signaling,
      which provide the reference frame with respect to which the centrosome reorients,
      result in the repositioning of the centrosome to the IS. 

PMID- 23874338
TI  - Tumor-altered dendritic cell function: implications for anti-tumor immunity.
AB  - Dendritic cells (DC) are key regulators of both innate and adaptive immunity, and
      the array of immunoregulatory functions exhibited by these cells is dictated by
      their differentiation, maturation, and activation status. Although a major role
      for these cells in the induction of immunity to pathogens has long been
      appreciated, data accumulated over the last several years has demonstrated that
      DC are also critical regulators of anti-tumor immune responses. However, despite
      the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered
      DC function has been observed in many cancer patients and tumor-bearing animals
      and is often associated with tumor immune escape. Such dysfunction has
      significant implications for both the induction of natural anti-tumor immune
      responses as well as the efficacy of immunotherapeutic strategies that target
      endogenous DC in situ or that employ exogenous DC as part of anti-cancer
      immunization maneuvers. In this review, the major types of tumor-altered DC
      function will be described, with emphasis on recent insights into the mechanistic
      bases for the inhibition of DC differentiation from hematopoietic precursors, the
      altered programing of DC precursors to differentiate into myeloid-derived
      suppressor cells or tumor-associated macrophages, the suppression of DC
      maturation and activation, and the induction of immunoregulatory DC by tumors,
      tumor-derived factors, and tumor-associated cells within the milieu of the tumor
      microenvironment. The impact of these tumor-altered cells on the quality of the
      overall anti-tumor immune response will also be discussed. Finally, this review
      will also highlight questions concerning tumor-altered DC function that remain
      unanswered, and it will address factors that have limited advances in the study
      of this phenomenon in order to focus future research efforts in the field on
      identifying strategies for interfering with tumor-associated DC dysfunction and
      improving DC-mediated anti-tumor immunity. 

PMID- 23874339
TI  - The Activity of CCL18 is Principally Mediated through Interaction with
      Glycosaminoglycans.
AB  - The CC chemokine ligand 18 (CCL18) was first identified as a chemoattractant for
      naive T cells. It has been reported to recruit T and B lymphocytes, and we show
      here, natural killer (NK) cells, but with low efficacy. Investigation of its
      ability to elicit G-protein-coupled signaling showed that it does not involve
      extracellular signal-regulated kinase (ERK) phosphorylation, and it is not able
      to induce receptor internalization, as assessed on CCR3. CCL18 has recently been
      reported to possess activities unrelated to cellular recruitment, but it had no
      effect on T lymphocyte proliferation. We postulated that a more potent
      chemoattractant may be produced under inflammatory conditions but only minor
      truncations were observed, with the major form being the full-length protein. In
      view of the lack of potent immunomodulatory properties, we wondered if binding to
      CCL18 by the tick chemokine binding proteins Evasin-1 and -4 was an artifact of
      the methods used, but complex formation was confirmed by size exclusion
      chromatography, and abrogation of its binding to, and antagonism of, CCR3. Its
      receptor has remained elusive since its cloning in 1997, although it has been
      reported to induce migration of breast cancer cells by signaling through PITPNM3,
      but we show that this receptor is not expressed on lymphocytes. We have developed
      a radiolabeled equilibrium competition binding assay and demonstrated that it
      bound with high affinity to peripheral blood leukocytes (PBLs), but the binding
      was displaced similarly by both unlabelled CCL18 as well as heparin. Both heparin
      binding and binding to PBLs are considerably abrogated by mutation of the BBXB
      motif in the 40s loop suggesting an essential role of the CCL18-glycosaminoglycan
      interaction. 

PMID- 23874340
TI  - CC Chemokine Ligand 20 and Its Cognate Receptor CCR6 in Mucosal T Cell Immunology
      and Inflammatory Bowel Disease: Odd Couple or Axis of Evil?
AB  - Chemokines and their cognate receptors have been identified as major factors
      initiating and governing cell movement and interaction. These ligands and their
      receptors are expressed on a wide variety of cells and act during steady-state
      migration as well as inflammatory recruitment. CCR6 is a non-promiscuous
      chemokine receptor that has only one known chemokine ligand, CCL20, and is
      present on B and T cells as well as dendritic cells (DCs). Two CD4(+) T cell
      populations with opposing functions present in the intestines and the mesenteric
      lymph nodes express CCR6: the pro-inflammatory TH17 and regulatory Treg cells.
      CCL20 is also present in the intestine and is strongly up-regulated after an
      inflammatory stimulus. Interestingly, this ligand is also expressed by TH17
      cells, which opens up the possibility of autocrine/paracrine signaling and,
      consequently, a self-perpetuating cycle of recruitment, thereby promoting
      inflammation. Recently, CCR6 has been implicated in inflammatory bowel disease
      (IBD) by genome wide association studies which showed an association between SNPs
      in the genomic region of the CCR6 gene and the inflammation. Furthermore, recent
      research targeting the biological function of CCR6 indicates a significant role
      for this chemokine receptor in the development of chronic IBD. It is therefore
      possible that IBD is facilitated by a disordered regulation of TH17 and Treg
      cells due to a disruption in the CCL20-CCR6 axis and consequently disturbed
      mucosal homeostasis. This review will summarize the literature on CCL20-CCR6 in
      mucosal immunology and will analyze the role this receptor-ligand axis has in
      chronic IBD. 

PMID- 23874341
TI  - Expression of MS4A and TMEM176 Genes in Human B Lymphocytes.
AB  - The MS4A gene family in humans includes CD20 and at least 15 other genes. CD20
      exists as homo-oligomers in the plasma membrane, however different MS4A proteins
      expressed in the same cell may hetero-oligomerize. Given the importance of CD20
      in B-cell function and as a therapeutic target, we sought to explore the
      potential for CD20 hetero-oligomerization with other MS4A proteins. We
      investigated expression in primary human B-cells of the four MS4A genes
      previously shown to be expressed in human B-cell lines (MS4A4A, MS4A6A, MS4A7,
      MS4A8B), as well as two genes comprising the closely related TMEM176 gene family,
      with a view to identifying candidates for future investigation at the protein
      level. TMEM176A and TMEM176B transcripts were either not detected, or were
      detected at relatively low levels in a minority of donor B-cell samples. MS4A4A
      and MS4A8B transcripts were not detected in any normal B-cell sample. MS4A6A and
      MS4A7 transcripts were detected at low levels in most samples, however the
      corresponding proteins were not at the plasma membrane when expressed as GFP
      conjugates in BJAB cells. We also examined expression of these genes in chronic
      lymphocytic leukemia (CLL), and found that it was similar to normal B-cells with
      two exceptions. First, whereas MS4A4A expression was undetected in normal B
      cells, it was expressed in 1/14 CLL samples. Second, compared to expression
      levels in normal B-cells, MS4A6A transcripts were elevated in 4/14 CLL samples.
      In summary, none of the MS4A/TMEM176 genes tested was expressed at high levels in
      normal or in most CLL B-cells. MS4A6A and MS4A7 were expressed at low levels in
      most B-cell samples, however the corresponding proteins may not be positioned at
      the plasma membrane. Altogether, these data suggest that CD20 normally does not
      form hetero-oligomers with other MS4A proteins and that there are unlikely to be
      other MS4A proteins in CLL that might provide useful alternate therapeutic
      targets. 

PMID- 23874342
TI  - Home sweet home: the tumor microenvironment as a haven for regulatory T cells.
AB  - CD4(+)Foxp3(+) regulatory T cells (Tregs) have a fundamental role in maintaining
      immune balance by preventing autoreactivity and immune-mediated pathology.
      However this role of Tregs extends to suppression of anti-tumor immune responses
      and remains a major obstacle in the development of anti-cancer vaccines and
      immunotherapies. This feature of Treg activity is exacerbated by the discovery
      that Treg frequencies are not only elevated in the blood of cancer patients, but
      are also significantly enriched within tumors in comparison to other sites. These
      observations have sparked off the quest to understand the processes through which
      Tregs become elevated in cancer-bearing hosts and to identify the specific
      mechanisms leading to their accumulation within the tumor microenvironment. This
      manuscript reviews the evidence for specific mechanisms of intra-tumoral Treg
      enrichment and will discuss how this information may be utilized for the purpose
      of manipulating the balance of tumor-infiltrating T cells in favor of anti-tumor
      effector cells. 

PMID- 23874343
TI  - Automated conserved non-coding sequence (CNS) discovery reveals differences in
      gene content and promoter evolution among grasses.
AB  - Conserved non-coding sequences (CNS) are islands of non-coding sequence that,
      like protein coding exons, show less divergence in sequence between related
      species than functionless DNA. Several CNSs have been demonstrated experimentally
      to function as cis-regulatory regions. However, the specific functions of most
      CNSs remain unknown. Previous searches for CNS in plants have either anchored on
      exons and only identified nearby sequences or required years of painstaking
      manual annotation. Here we present an open source tool that can accurately
      identify CNSs between any two related species with sequenced genomes, including
      both those immediately adjacent to exons and distal sequences separated by >12 kb
      of non-coding sequence. We have used this tool to characterize new motifs,
      associate CNSs with additional functions, and identify previously undetected
      genes encoding RNA and protein in the genomes of five grass species. We provide a
      list of 15,363 orthologous CNSs conserved across all grasses tested. We were also
      able to identify regulatory sequences present in the common ancestor of grasses
      that have been lost in one or more extant grass lineages. Lists of orthologous
      gene pairs and associated CNSs are provided for reference inbred lines of
      arabidopsis, Japonica rice, foxtail millet, sorghum, brachypodium, and maize. 

PMID- 23874344
TI  - Effector candidates in the secretome of Piriformospora indica, a ubiquitous plant
      associated fungus.
AB  - One of the emerging systems in plant-microbe interaction is the study of
      proteins, referred to as effectors, secreted by microbes in order to modulate
      host cells function and structure and to promote microbial growth on plant
      tissue. Current knowledge on fungal effectors derives mainly from biotrophic and
      hemibiotrophic plant fungal pathogens that have a limited host range. Here, we
      focus on effectors of Piriformospora indica, a soil borne endophyte forming
      intimate associations with roots of a wide range of plant species. Complete
      genome sequencing provides an opportunity to investigate the role of effectors
      during the interaction of this mutualistic fungus with plants. We describe in
      silico analyses to predict effectors of P. indica and we explore effector
      features considered here to mine a high priority protein list for functional
      analysis. 

PMID- 23874345
TI  - Perspectives for using genetically encoded fluorescent biosensors in plants.
AB  - Genetically encoded fluorescent biosensors have long proven to be excellent tools
      for quantitative live imaging, but sensor applications in plants have been
      lacking behind those in mammalian systems with respect to the variety of sensors
      and tissue types used. How can this be improved, and what can be expected for the
      use of genetically encoded fluorescent biosensors in plants in the future? In
      this review, we present a table of successful physiological experiments in plant
      tissue using fluorescent biosensors, and draw some conclusions about the specific
      challenges plant cell biologists are faced with and some of the ways they have
      been overcome so far. 

PMID- 23874347
TI  - Interspecific coordination and intraspecific plasticity of fine root traits in
      North American temperate tree species.
AB  - Fine roots play an important role in nutrient and water absorption and hence
      overall tree performance. However, current understanding of the ecological role
      of belowground traits lags considerably behind those of aboveground traits. In
      this study, we used data on specific root length (SRL), fine root diameter (D)
      and branching intensity (BI) of two datasets to examine interspecific trait
      coordination as well as intraspecific trait variation across ontogenetic stage
      and soil conditions (i.e., plasticity). The first dataset included saplings of 12
      North American temperate tree species grown in monocultures in a common garden
      experiment to examine interspecific trait coordination. The second dataset
      included adult and juvenile individuals of four species (present in both
      datasets) co-occurring in natural forests on contrasting soils (i.e., humid
      organic, mesic, and xeric podzolic).The three fine root traits investigated were
      strongly coordinated, with high SRL being related to low D and high BI. Fine root
      traits and aboveground life-strategies (i.e., relative growth rate) were weakly
      coordinated and never significant. Intraspecific responses to changes in
      ontogenetic stage or soil conditions were trait dependent. SRL was significantly
      higher in juveniles compared to adults for Abies balsamea and Acer rubrum, but
      did not vary with soil condition. BI did not vary significantly with either
      ontogeny or soil conditions, while D was generally significantly lower in
      juveniles and higher in humid organic soils. D also had the least total
      variability most of which was due to changes in the environment (plasticity).
      This study brings support for the emerging evidence for interspecific root trait
      coordination in trees. It also indicates that intraspecific responses to both
      ontogeny and soil conditions are trait dependent and less concerted. D appears to
      be a better indicator of environmental change than SRL and BI. 

PMID- 23874346
TI  - ARP2/3 localization in Arabidopsis leaf pavement cells: a diversity of
      intracellular pools and cytoskeletal interactions.
AB  - In plant cells the actin cytoskeleton adopts many configurations, but is best
      understood as an unstable, interconnected track that rearranges to define the
      patterns of long distance transport of organelles during growth. Actin filaments
      do not form spontaneously; instead filament nucleators, such as the
      evolutionarily conserved actin-related protein (ARP) 2/3 complex, can efficiently
      generate new actin filament networks when in a fully activated state. A growing
      number of genetic experiments have shown that ARP2/3 is necessary for
      morphogenesis in processes that range from tip growth during root nodule
      formation to the diffuse polarized growth of leaf trichomes and pavement cells.
      Although progress has been rapid in the identification of proteins that function
      in series to positively regulate ARP2/3, less has been learned about the actual
      function of ARP2/3 in cells. In this paper, we analyze the localization of ARP2/3
      in Arabidopsis leaf pavement cells. We detect a pool of ARP2/3 in the nucleus,
      and also find that ARP2/3 is efficiently and specifically clustered on multiple
      organelle surfaces and associates with both the actin filament and microtubule
      cytoskeletons. Our mutant analyses and ARP2/3 and actin double labeling
      experiments indicate that the clustering of ARP2/3 on organelle surfaces and an
      association with actin bundles does not necessarily reflect an active pool of
      ARP2/3, and instead most of the complex appears to exist as a latent organelle
      associated pool. 

PMID- 23874348
TI  - Reprogramming of plants during systemic acquired resistance.
AB  - Genome-wide microarray analyses revealed that during biological activation of
      systemic acquired resistance (SAR) in Arabidopsis, the transcript levels of
      several hundred plant genes were consistently up- (SAR(+) genes) or down
      regulated (SAR(-) genes) in systemic, non-inoculated leaf tissue. This
      transcriptional reprogramming fully depended on the SAR regulator FLAVIN
      DEPENDENT MONOOXYGENASE1 (FMO1). Functional gene categorization showed that genes
      associated with salicylic acid (SA)-associated defenses, signal transduction,
      transport, and the secretory machinery are overrepresented in the group of SAR(+)
      genes, and that the group of SAR(-) genes is enriched in genes activated via the
      jasmonate (JA)/ethylene (ET)-defense pathway, as well as in genes associated with
      cell wall remodeling and biosynthesis of constitutively produced secondary
      metabolites. This suggests that SAR-induced plants reallocate part of their
      physiological activity from vegetative growth towards SA-related defense
      activation. Alignment of the SAR expression data with other microarray
      information allowed us to define three clusters of SAR(+) genes. Cluster I
      consists of genes tightly regulated by SA. Cluster II genes can be expressed
      independently of SA, and this group is moderately enriched in H2O2- and abscisic
      acid (ABA)-responsive genes. The expression of the cluster III SAR(+) genes is
      partly SA-dependent. We propose that SA-independent signaling events in early
      stages of SAR activation enable the biosynthesis of SA and thus initiate SA
      dependent SAR signaling. Both SA-independent and SA-dependent events tightly co
      operate to realize SAR. SAR(+) genes function in the establishment of diverse
      resistance layers, in the direct execution of resistance against different (hemi
      )biotrophic pathogen types, in suppression of the JA- and ABA-signaling pathways,
      in redox homeostasis, and in the containment of defense response activation. Our
      data further indicated that SAR-associated defense priming can be realized by
      partial pre-activation of particular defense pathways. 

PMID- 23874350
TI  - More beneath the surface? Root versus shoot antifungal plant defenses.

PMID- 23874349
TI  - Regulation of leaf hydraulics: from molecular to whole plant levels.
AB  - The water status of plant leaves is dependent on both stomatal regulation and
      water supply from the vasculature to inner tissues. The present review addresses
      the multiple physiological and mechanistic facets of the latter process. Inner
      leaf tissues contribute to at least a third of the whole resistance to water flow
      within the plant. Physiological studies indicated that leaf hydraulic conductance
      (K leaf) is highly dependent on the anatomy, development and age of the leaf and
      can vary rapidly in response to physiological or environmental factors such as
      leaf hydration, light, temperature, or nutrient supply. Differences in venation
      pattern provide a basis for variations in K leaf during development and between
      species. On a short time (hour) scale, the hydraulic resistance of the vessels
      can be influenced by transpiration-induced cavitations, wall collapses, and
      changes in xylem sap composition. The extravascular compartment includes all
      living tissues (xylem parenchyma, bundle sheath, and mesophyll) that transport
      water from xylem vessels to substomatal chambers. Pharmacological inhibition and
      reverse genetics studies have shown that this compartment involves water channel
      proteins called aquaporins (AQPs) that facilitate water transport across cell
      membranes. In many plant species, AQPs are present in all leaf tissues with a
      preferential expression in the vascular bundles. The various mechanisms that
      allow adjustment of K leaf to specific environmental conditions include
      transcriptional regulation of AQPs and changes in their abundance, trafficking,
      and intrinsic activity. Finally, the hydraulics of inner leaf tissues can have a
      strong impact on the dynamic responses of leaf water potential and stomata, and
      as a consequence on plant carbon economy and leaf expansion growth. The
      manipulation of these functions could help optimize the entire plant performance
      and its adaptation to extreme conditions over short and long time scales. 

PMID- 23874351
TI  - The hidden factors in impact factors: a perspective from Brazilian science.

PMID- 23874353
TI  - MicroRNA discovery by similarity search to a database of RNA-seq profiles.
AB  - In silico generated search for microRNAs (miRNAs) has been driven by methods
      compiling structural features of the miRNA precursor hairpin, as well as to some
      degree combining this with the analysis of RNA-seq profiles for which the miRNA
      typically leave the drosha/dicer fingerprint of 1-2 ~22 nt blocks of reads
      corresponding to the mature and star miRNA. In complement to the previous
      methods, we present a study where we systematically exploit these patterns of
      read profiles. We created two datasets comprised of 2540 and 4795 read profiles
      obtained after preprocessing short RNA-seq data from miRBase and ENCODE,
      respectively. Out of 4795 ENCODE read profiles, 1361 are annotated as non-coding
      RNAs (ncRNAs) and of which 285 are further annotated as miRNAs. Using
      deepBlockAlign (dba), we align ncRNA read profiles from ENCODE against the
      miRBase read profiles (cleaned for "self-matches") and are able to separate
      ENCODE miRNAs from the other ncRNAs by a Matthews Correlation Coefficient (MCC)
      of 0.8 and obtain an area under the curve of 0.93. Based on the dba score cut-off
      of 0.7 at which we observed the maximum MCC of 0.8, we predict 523 novel miRNA
      candidates. An additional RNA secondary structure analysis reveal that 42 of the
      candidates overlap with predicted conserved secondary structure. Further analysis
      reveal that the 523 miRNA candidates are located in genomic regions with MAF
      block (UCSC) fragmentation and poor sequence conservation, which in part might
      explain why they have been overlooked in previous efforts. We further analyzed
      known human and mouse miRNA read profiles and found two distinct classes; the
      first containing two blocks and the second containing >2 blocks of reads. Also
      the latter class holds read profiles that have less well defined arrangement of
      reads in comparison to the former class. On comparison of miRNA read profiles
      from plants and animals, we observed kingdom specific read profiles that are
      distinct in terms of both length and distribution of reads within the read
      profiles to each other. All the data, as well as a server to search miRBase read
      profiles by uploading a BED file, is available at http://rth.dk/resources/mirdba.

PMID- 23874354
TI  - Improvement of Agrobacterium-mediated transformation of cucumber (Cucumis sativus
      L.) by combination of vacuum infiltration and co-cultivation on filter paper
      wicks.
AB  - An improved method for genetic transformation of cucumber (Cucumis sativus L. cv.
      Shinhokusei No. 1) was developed. Vacuum infiltration of cotyledonary explants
      with Agrobacterium suspension enhanced the efficiency of Agrobacterium infection
      in the proximal regions of explants. Co-cultivation on filter paper wicks
      suppressed necrosis of explants, leading to increased regeneration efficiency.
      Putative transgenic plants were screened by kanamycin resistance and green
      fluorescent protein (GFP) fluorescence, and integration of the transgene into the
      cucumber genome was confirmed by genomic polymerase chain reaction (PCR) and
      Southern blotting. These transgenic plants grew normally and T1 seeds were
      obtained from 7 lines. Finally, stable integration and transmission of the
      transgene in T1 generations were confirmed by GFP fluorescence and genomic PCR.
      The average transgenic efficiency for producing cucumbers with our method was
      11.9 +/- 3.5 %, which is among the highest values reported until date using
      kanamycin as a selective agent.

PMID- 23874352
TI  - Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond.
AB  - Micronuclei (MN) are extra-nuclear bodies that contain damaged chromosome
      fragments and/or whole chromosomes that were not incorporated into the nucleus
      after cell division. MN can be induced by defects in the cell repair machinery
      and accumulation of DNA damages and chromosomal aberrations. A variety of
      genotoxic agents may induce MN formation leading to cell death, genomic
      instability, or cancer development. In this review, the genetic and epigenetic
      mechanisms of MN formation after various clastogenic and aneugenic effects on
      cell division and cell cycle are described. The knowledge accumulated in
      literature on cytotoxicity of various genotoxins is precisely reflected and
      individual sensitivity to MN formation due to single gene polymorphisms is
      discussed. The importance of rapid MN scoring with respect to the cytokinesis
      block micronucleus assay is also evaluated. 

PMID- 23874355
TI  - Development of an automated, real time surveillance tool for predicting
      readmissions at a community hospital.
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services' Readmissions
      Reduction Program adjusts payments to hospitals based on 30-day readmission rates
      for patients with acute myocardial infarction, heart failure, and pneumonia. This
      holds hospitals accountable for a complex phenomenon about which there is little
      evidence regarding effective interventions. Further study may benefit from a
      method for efficiently and inexpensively identifying patients at risk of
      readmission. Several models have been developed to assess this risk, many of
      which may not translate to a U.S. community hospital setting. OBJECTIVE: To
      develop a real-time, automated tool to stratify risk of 30-day readmission at a
      semirural community hospital. METHODS: A derivation cohort was created by
      extracting demographic and clinical variables from the data repository for adult
      discharges from calendar year 2010. Multivariate logistic regression identified
      variables that were significantly associated with 30-day hospital readmission.
      Those variables were incorporated into a formula to produce a Risk of Readmission
      Score (RRS). A validation cohort from 2011 assessed the predictive value of the
      RRS. A SQL stored procedure was created to calculate the RRS for any patient and
      publish its value, along with an estimate of readmission risk and other factors,
      to a secure intranet site. RESULTS: Eleven variables were significantly
      associated with readmission in the multivariate analysis of each cohort. The RRS
      had an area under the receiver operating characteristic curve (c-statistic) of
      0.74 (95% CI 0.73-0.75) in the derivation cohort and 0.70 (95% CI 0.69-0.71) in
      the validation cohort. CONCLUSION: Clinical and administrative data available in
      a typical community hospital database can be used to create a validated,
      predictive scoring system that automatically assigns a probability of 30-day
      readmission to hospitalized patients. This does not require manual data
      extraction or manipulation and uses commonly available systems. Additional study
      is needed to refine and confirm the findings.

PMID- 23874356
TI  - Do language fluency and other socioeconomic factors influence the use of PubMed
      and MedlinePlus?
AB  - BACKGROUND: Increased usage of MedlinePlus by Spanish-speakers was observed after
      introduction of MedlinePlus in Spanish. This probably reflects increased usage of
      MEDLINE and PubMed by those with greater fluency in the language in which it is
      presented; but this has never been demonstrated in English speakers. Evidence
      that lack of English fluency deters international healthcare personnel from using
      PubMed could support the use of multi-language search tools like Babel-MeSH.
      OBJECTIVES: This study aims to measure the effects of language fluency and other
      socioeconomic factors on PubMed MEDLINE and MedlinePlus access by international
      users. METHODS: We retrospectively reviewed server pageviews of PubMed and
      MedlinePlus from various periods of time, and analyzed them against country
      statistics on language fluency, GDP, literacy rate, Internet usage, medical
      schools, and physicians per capita, to determine whether they were associated.
      RESULTS: We found fluency in English to be positively associated with pageviews
      of PubMed and MedlinePlus in countries with high literacy rates. Spanish was
      generally found to be positively associated with pageviews of MedlinePlus en
      Espanol. The other parameters also showed varying degrees of association with
      pageviews. CONCLUSIONS: After adjusting for the other factors investigated in
      this study, language fluency was a consistently significant predictor of the use
      of PubMed, MedlinePlus English and MedlinePlus en Espanol. This study may support
      the need for multi-language search tools and may increase access of health
      information resources from non-English speaking countries.

PMID- 23874357
TI  - An information systems model of the determinants of electronic health record use.
AB  - OBJECTIVES: The prominence given to universal implementation of electronic health
      record (EHR) systems in U.S. health care reform, underscores the importance of
      devising reliable measures of factors that predict medical care providers' use of
      EHRs. This paper presents an easily administered provider survey instrument that
      includes measures corresponding to core dimensions of DeLone and McClean's (D &
      M) model of information system success. METHODS: Study data came from self
      administered surveys completed by 460 primary care providers, who had recently
      begun using an EHR. RESULTS: Based upon assessment of psychometric properties of
      survey items, a revised D&M causal model was formulated that included four
      measures of the determinants of EHR use (system quality, IT support, ease of use,
      user satisfaction) and five indicators of provider beliefs about the impact on an
      individual's clinical practice. A structural equation model was estimated that
      demonstrated a high level of inter-correlation between the four scales measuring
      determinants of EHR use. All four variables had positive association with each of
      the five individual impact measures. Consistent with our revised D&M model, the
      association of system quality and IT support with the individual impact measures
      was entirely mediated by ease of use and user satisfaction. CONCLUSIONS: Survey
      research provides important insights into provider experiences with EHR.
      Additional studies are in progress to investigate how the variables constructed
      for this study are related to direct measures of EHR use.

PMID- 23874358
TI  - Medical student appraisal: applications for bedside patient education.
AB  - BACKGROUND: Medical students are often afforded the privilege of counselling
      patients. In the past resources were limited to pen and paper or anatomic models.
      The evolution of mobile applications allows for limitless access to resources
      that facilitate bedside patient education. OBJECTIVES: To evaluate the utility of
      six applications in patient education and promote awareness of implementing
      mobile resources in clinical care. METHODS: Six medical students rotating on
      various clerkships evaluated a total of six mobile applications. Strengths,
      limitations, and suggested uses in clinical care were identified. Applications
      included MeditoonsTM, VisiblePatientTM, DrawMDTM, CardioTeachTM, Visual
      AnatomyTM, and 360 degrees  Patient Education SuiteTM. Data was generated from
      narrative responses supplied by each student during their evaluation period.
      RESULTS: Bedside teaching was enhanced by professional illustrations and
      animations depicting anatomy and pathophysiology. Impromptu teaching was
      facilitated, as resources were conveniently available on a student's smartphone
      or tablet. The ability to annotate and modify images and subsequently email to
      patients was an extraordinary improvement in provider-patient communication.
      Universal limitations included small smartphone screens and the novelty of new
      technology. DISCUSSION: Mobile applications have the potential to greatly enhance
      patient education and simultaneously build rapport. Endless opportunities exist
      for their integration in clinical practice, particularly for new diagnoses,
      consent for procedures, and at time of discharge. Providers should be encouraged
      to try new applications and utilize them with patients.

PMID- 23874359
TI  - Diagnostic performance of electronic syndromic surveillance systems in acute
      care: a systematic review.
AB  - CONTEXT: Healthcare Electronic Syndromic Surveillance (ESS) is the systematic
      collection, analysis and interpretation of ongoing clinical data with subsequent
      dissemination of results, which aid clinical decision-making. OBJECTIVE: To
      evaluate, classify and analyze the diagnostic performance, strengths and
      limitations of existing acute care ESS systems. DATA SOURCES: All available to us
      studies in Ovid MEDLINE, Ovid EMBASE, CINAHL and Scopus databases, from as early
      as January 1972 through the first week of September 2012. STUDY SELECTION:
      Prospective and retrospective trials, examining the diagnostic performance of
      inpatient ESS and providing objective diagnostic data including sensitivity,
      specificity, positive and negative predictive values. DATA EXTRACTION: Two
      independent reviewers extracted diagnostic performance data on ESS systems,
      including clinical area, number of decision points, sensitivity and specificity.
      Positive and negative likelihood ratios were calculated for each healthcare ESS
      system. A likelihood matrix summarizing the various ESS systems performance was
      created. RESULTS: The described search strategy yielded 1639 articles. Of these,
      1497 were excluded on abstract information. After full text review, abstraction
      and arbitration with a third reviewer, 33 studies met inclusion criteria,
      reporting 102,611 ESS decision points. The yielded I2 was high (98.8%),
      precluding meta-analysis. Performance was variable, with sensitivities ranging
      from 21% -100% and specificities ranging from 5%-100%. CONCLUSIONS: There is
      significant heterogeneity in the diagnostic performance of the available ESS
      implements in acute care, stemming from the wide spectrum of different clinical
      entities and ESS systems. Based on the results, we introduce a conceptual
      framework using a likelihood ratio matrix for evaluation and meaningful
      application of future, frontline clinical decision support systems.

PMID- 23874360
TI  - Physician specialty and variations in adoption of electronic health records.
AB  - OBJECTIVE: Efforts to promote adoption of electronic health records (EHRs) have
      focused on primary care physicians, who are now expected to exchange data
      electronically with other providers, including specialists. However, the
      variation of EHR adoption among specialists is underexplored. METHODS: We
      conducted a retrospective cross-sectional study to determine the association
      between physician specialty and the prevalence of EHR adoption, and a
      retrospective serial cross-sectional study to determine the association of
      physician specialty and the rate of EHR adoption over time. We used the 2005-2009
      National Ambulatory Medical Care Survey. We considered fourteen specialties, and
      four definitions of EHR adoption (any EHR, basic EHR, full EHR, and a novel
      definition of EHR sophistication). We used multivariable logistic regression, and
      adjusted for several covariates (geography, practice characteristics, revenue
      characteristics, physician degree). RESULTS: Physician specialty was
      significantly associated with EHR adoption, regardless of the EHR definition,
      after adjusting for covariates. Psychiatrists, dermatologists, pediatricians,
      ophthalmologists, and general surgeons were significantly less likely to adopt
      EHRs, compared to the reference group of family medicine/general practitioners.
      After adjustment for covariates, these specialties were 44-94% less likely to
      adopt EHRs than the reference group. EHR adoption increased in all specialties,
      by approximately 40% per year. The rate of EHR adoption over time did not
      significantly vary by specialty. CONCLUSIONS: Although EHR adoption is increasing
      in all specialties, adoption varies widely by specialty. In order to insure each
      individual's network of providers can electronically share data, widespread
      adoption of EHRs is needed across all specialties.

PMID- 23874361
TI  - Debunking health IT usability myths.
AB  - Poor usability is a threat to patient safety and linked to productivity loss,
      workflow disruption, user frustration, sub-optimal product use and system de
      installations. Although usability is receiving more attention nationally and
      internationally, myths about usability persist. This editorial debunks five
      common myths about usability (1) usability only concerns the look and feel of a
      product and is, therefore, only a minor concern, (2) usability is not measurable,
      (3) usability stifles innovation, (4) vendors are solely responsible for product
      usability, and (5) usability methods are not practical for use in healthcare. 

PMID- 23874363
TI  - Effects of automated immunization registry reporting via an electronic health
      record deployed in community practice settings.
AB  - BACKGROUND: Among the expected benefits of electronic health records (EHRs) is
      increased reporting of public health information, such as immunization status.
      State and local immunization registries aid control of vaccine-preventable
      diseases and help offset fragmentation in healthcare, but reporting is often slow
      and incomplete. The Primary Care Information Project (PCIP), an initiative of the
      NYC Department of Health and Mental Hygiene, has implemented EHRs with
      immunization reporting capability in community settings. OBJECTIVE AND METHODS:
      To evaluate the effect of automated reporting via an EHR on use and efficiency of
      reporting to the NY Citywide Immunization Registry, we conducted a secondary
      analysis of 1.7 million de-identified records submitted between January 2007 and
      June 2011 by 217 primary care practices enrolled in PCIP, pre and post launch of
      automated reporting via an EHR. We examined differences in records submitted per
      day, lag time, and documentation of eligibility for subsidized vaccines. RESULTS:
      Mean submissions per day did not change. Automated submissions of new and
      historical records increased by 18% and 98% respectively. Submissions within 14
      days increased from 84% to 87%, and within 2 days increased from 60% to 77%.
      Median lag time decreased from 13 to 10 days. Documentation of eligibility
      decreased. Results are significant at p<0.001. CONCLUSIONS: Significant
      improvements in registry use and efficiency of reporting were found after launch
      of automated reporting via an EHR. A decrease in eligibility documentation was
      attributed to EHR workflow. The limitations to comprehensive evaluation found in
      these data, which were extracted from a registry initiated prior to widespread
      EHR implementation suggests that reliable evaluation of immunization reporting
      via the EHR may require modifications to legacy registry databases.

PMID- 23874362
TI  - Enhancement of decision rules to increase generalizability and performance of the
      rule-based system assessing risk for pressure ulcer.
AB  - BACKGROUND: A rule-based system, the Braden Scale based Automated Risk Assessment
      Tool (BART), was developed to assess risk for pressure ulcer in a previous study.
      However, the BART illustrated two major areas in need of improvement, which were:
      1) the enhancement of decision rules and 2) validation of generalizability to
      increase performance of BART. OBJECTIVES: To enhance decision rules and validate
      generalizability of the enhanced BART. METHOD: Two layers of decision rule
      enhancement were performed: 1) finding additional data items with the experts and
      2) validating logics of decision rules utilizing a guideline modeling language.
      To refine the decision rules of the BART further, a survey study was conducted to
      ascertain the operational level of patient status description of the Braden
      Scale. The enhanced BART (BART2) was designed to assess levels of pressure ulcer
      risk of patients (N = 99) whose data were collected by the nurses. The patients'
      level of pressure ulcer risk was assessed by the nurses using a Braden Scale, by
      an expert using a Braden Scale, and by the automatic BART2 electronic risk
      assessment. SPSS statistical software version 20 (IBM, 2011) was used to test the
      agreement between the three different risk assessments performed on each patient.
      RESULTS: The level of agreement between the BART2 and the expert pressure ulcer
      assessments was "very good (0.83)". The sensitivity and the specificity of the
      BART2 were 86.8% and 90.3% respectively. CONCLUSION: This study illustrated
      successful enhancement of decision rules and increased generalizability and
      performance of the BART2. Although the BART2 showed a "very good" level of
      agreement (kappa = 0.83) with an expert, the data reveal a need to improve the
      moisture parameter of the Braden Scale. Once the moisture parameter has been
      improved, BART2 will improve the quality of care, while accurately identifying
      the patients at risk for pressure ulcers.

PMID- 23874364
TI  - Usability characteristics of self-administered computer-assisted interviewing in
      the emergency department: factors affecting ease of use, efficiency, and entry
      error.
AB  - OBJECTIVE: Self-administered computer-assisted interviewing (SACAI) gathers
      accurate information from patients and could facilitate Emergency Department (ED)
      diagnosis. As part of an ongoing research effort whose long-range goal is to
      develop automated medical interviewing for diagnostic decision support, we
      explored usability attributes of SACAI in the ED. METHODS: Cross-sectional study
      at two urban, academic EDs. Convenience sample recruited daily over six weeks.
      Adult, non-level I trauma patients were eligible. We collected data on ease of
      use (self-reported difficulty, researcher documented need for help), efficiency
      (mean time-per-click on a standardized interview segment), and error (self-report
      age mismatched with age derived from electronic health records) when using SACAI
      on three different instruments: Elo TouchSystems ESY15A2 (finger touch), Toshiba
      M200 (with digitizer pen), and Motion C5 (with digitizer pen). We calculated
      descriptive statistics and used regression analysis to evaluate the impact of
      patient and computer factors on time-per-click. RESULTS: 841 participants
      completed all SACAI questions. Few (<1%) thought using the touch computer to
      ascertain medical information was difficult. Most (86%) required no assistance.
      Participants needing help were older (54 +/- 19 vs. 40 +/- 15 years, p<0.001) and
      more often lacked internet at home (13.4% vs. 7.3%, p = 0.004). On multivariate
      analysis, female sex (p<0.001), White (p<0.001) and other (p = 0.05) race (vs.
      Black race), younger age (p<0.001), internet access at home (p<0.001), high
      school graduation (p = 0.04), and touch screen entry (vs. digitizer pen) (p =
      0.01) were independent predictors of decreased time-per-click. Participant
      misclick errors were infrequent, but, in our sample, occurred only during
      interviews using a digitizer pen rather than a finger touch-screen interface
      (1.9% vs. 0%, p = 0.09). DISCUSSION: Our results support the facility of
      interactions between ED patients and SACAI. Demographic factors associated with
      need for assistance or slower interviews could serve as important triggers to
      offering human support for SACAI interviews during implementation. CONCLUSION:
      Understanding human-computer interactions in real-world clinical settings is
      essential to implementing automated interviewing as means to a larger long-term
      goal of enhancing clinical care, diagnostic accuracy, and patient safety.

PMID- 23874365
TI  - Association of Medical Directors of Information Systems consensus on inpatient
      electronic health record documentation.
AB  - In 2013, electronic documentation of clinical care stands at a crossroads. The
      benefits of creating digital notes are at risk of being overwhelmed by the
      inclusion of easily importable detail. Providers are the primary authors of
      encounters with patients. We must document clearly our understanding of patients
      and our communication with them and our colleagues. We want to document
      efficiently to meet without exceeding documentation guidelines. We copy and paste
      documentation, because it not only simplifies the documentation process
      generally, but also supports meeting coding and regulatory requirements
      specifically. Since the primary goal of our profession is to spend as much time
      as possible listening to, understanding and helping patients, clinicians need
      information technology to make electronic documentation easier, not harder. At
      the same time, there should be reasonable restrictions on the use of copy and
      paste to limit the growing challenge of 'note bloat'. We must find the right
      balance between ease of use and thoughtless documentation. The guiding principles
      in this document may be used to launch an interdisciplinary dialogue that
      promotes useful and necessary documentation that best facilitates efficient
      information capture and effective display. 

PMID- 23874366
TI  - Lessons learned for collaborative clinical content development.
AB  - BACKGROUND: Site-specific content configuration of vendor-based Electronic Health
      Records (EHRs) is a vital step in the development of standardized and
      interoperable content that can be used for clinical decision-support, reporting,
      care coordination, and information exchange. The multi-site, multi-stakeholder
      Acute Care Documentation (ACD) project at Partners Healthcare Systems (PHS) aimed
      to develop highly structured clinical content with adequate breadth and depth to
      meet the needs of all types of acute care clinicians at two academic medical
      centers. The Knowledge Management (KM) team at PHS led the informatics and
      knowledge management effort for the project. OBJECTIVES: We aimed to evaluate the
      role, governance, and project management processes and resources for the KM
      team's effort as part of the standardized clinical content creation. METHODS: We
      employed the Center for Disease Control's six step Program Evaluation Framework
      to guide our evaluation steps. We administered a forty-four question, open-ended,
      semi-structured voluntary survey to gather focused, credible evidence from
      members of the KM team. Qualitative open-coding was performed to identify themes
      for lessons learned and concluding recommendations. RESULTS: Six surveys were
      completed. Qualitative data analysis informed five lessons learned and thirty
      specific recommendations associated with the lessons learned. The five lessons
      learned are: 1) Assess and meet knowledge needs and set expectations at the start
      of the project; 2) Define an accountable decision-making process; 3) Increase
      team meeting moderation skills; 4) Ensure adequate resources and competency
      training with online asynchronous collaboration tools; 5) Develop focused, goal
      oriented teams and supportive, consultative service based teams. CONCLUSIONS:
      Knowledge management requirements for the development of standardized clinical
      content within a vendor-based EHR among multi-stakeholder teams and sites
      include: 1) assessing and meeting informatics knowledge needs, 2) setting
      expectations and standardizing the process for decision-making, and 3) ensuring
      the availability of adequate resources and competency training.

PMID- 23874367
TI  - Droplet based microfluidic fabrication of designer microparticles for
      encapsulation applications.
AB  - Developing carriers of active ingredients with pre-determined release kinetics is
      a main challenge in the field of controlled release. In this work, we fabricate
      designer microparticles as carriers of active ingredients using droplet
      microfluidics. We show that monodisperse droplet templates do not necessarily
      produce monodisperse particles. Magnetic stirring, which is often used to enhance
      the droplet solidification rate, can promote breakup of the resultant
      microparticles into fragments; with an increase in the stirring time,
      microparticles become smaller in average size and more irregular in shape. Thus,
      the droplet solidification conditions affect the size, size distribution and
      morphology of the fabricated particles, and these attributes of the
      microparticles strongly influence their release kinetics. The smaller the average
      size of the microparticles is, the higher the initial release rate is. The
      release kinetics of drug carriers is strongly related to their characteristics.
      The understanding of this relationship enables the fabrication of tailor-designed
      carriers with a specified release rate, and even programmed release to meet the
      needs of applications that require a complex release profile of the active
      ingredients. 

PMID- 23874368
TI  - Behavior of liquid plugs at bifurcations in a microfluidic tree network.
AB  - Flows in complex geometries, such as porous media or biological networks, often
      contain plugs of liquid flowing within air bubbles. These flows can be modeled in
      microfluidic devices in which the geometric complexity is well defined and
      controlled. We study the flow of wetting liquid plugs in a bifurcating network of
      micro-channels. In particular, we focus on the process by which the plugs divide
      as they pass each bifurcation. The key events are identified, corresponding to
      large modifications of the interface curvature, the formation of new interfaces,
      or the division of a single interface into two new ones. The timing of the
      different events and the amplitude of the curvature variations are analyzed in
      view of the design of an event-driven model of flow in branching micro-networks.
      They are found to collapse onto a master curve dictated by the network geometry. 

PMID- 23874369
TI  - Monolithic integration of fine cylindrical glass microcapillaries on silicon for
      electrophoretic separation of biomolecules.
AB  - We demonstrate monolithic integration of fine cylindrical glass microcapillaries
      (diameter ~1 MUm) on silicon and evaluate their performance for electrophoretic
      separation of biomolecules. Such microcapillaries are achieved through thermal
      reflow of a glass layer on microstructured silicon whereby slender voids are
      moulded into cylindrical tubes. The process allows self-enclosed microcapillaries
      with a uniform profile. A simplified method is also described to integrate the
      microcapillaries with a sample-injection cross without the requirement of glass
      etching. The 10-mm-long microcapillaries sustain field intensities up to 90 kV/m
      and limit the temperature excursions due to Joule heating to a few degrees
      Celsius only. 

PMID- 23874370
TI  - Principal component analysis based feature extraction approach to identify
      circulating microRNA biomarkers.
AB  - The discovery and characterization of blood-based disease biomarkers are
      clinically important because blood collection is easy and involves relatively
      little stress for the patient. However, blood generally reflects not only
      targeted diseases, but also the whole body status of patients. Thus, the
      selection of biomarkers may be difficult. In this study, we considered miRNAs as
      biomarker candidates for several reasons. First, since miRNAs were discovered
      relatively recently, they have not yet been tested extensively. Second, since the
      number of miRNAs is relatively limited, selection is expected to be easy. Third,
      since they are known to play critical roles in a wide range of biological
      processes, their expression may be disease specific. We applied a newly proposed
      method to select combinations of miRNAs that discriminate between healthy
      controls and each of 14 diseases that include 5 cancers. A new feature selection
      method is based on principal component analysis. Namely this method does not
      require knowledge of whether each sample was derived from a disease patient or a
      healthy control. Using this method, we found that hsa-miR-425, hsa-miR-15b, hsa
      miR-185, hsa-miR-92a, hsa-miR-140-3p, hsa-miR-320a, hsa-miR-486-5p, hsa-miR-16,
      hsa-miR-191, hsa-miR-106b, hsa-miR-19b, and hsa-miR-30d were potential
      biomarkers; combinations of 10 of these miRNAs allowed us to discriminate each
      disease included in this study from healthy controls. These 12 miRNAs are
      significantly up- or downregulated in most cancers and other diseases, albeit in
      a cancer- or disease-specific combinatory manner. Therefore, these 12 miRNAs were
      also previously reported to be cancer- and disease-related miRNAs. Many disease
      specific KEGG pathways were also significantly enriched by target genes of up
      /downregulated miRNAs within several combinations of 10 miRNAs among these 12
      miRNAs. We also selected miRNAs that could discriminate one disease from another
      or from healthy controls. These miRNAs were found to be largely overlapped with
      miRNAs that discriminate each disease from healthy controls. 

PMID- 23874371
TI  - CD20 antibody primes B lymphocytes for type I interferon production.
AB  - CD20 is a B cell surface marker that is expressed in various stages in B
      lymphocytes and certain lymphomas. Clinical administration of CD20 antibody, such
      as rituximab, is used widely to treat human B-cell lymphomas and other diseases.
      However, CD20 antibody failed to treat systemic lupus erythematosus (SLE or
      lupus). The reason for the failure is currently unknown. Type I interferons (IFN)
      are a major component for the host innate immunity, and a key pathogenic factor
      in lupus. We found that CD20 antibody potentiated human B cells for its
      production of IFNs in vitro. This function was specific to CD20-expressing cells
      and the potentiation function seems to be instant. In addition, ectopic
      expression of CD20 in non-B-lymphocytes increased the IFN promoter reporter
      activities. Because IFNs are a key pathogenic factor in lupus, our data suggest
      that, in the presence of virus infection, the CD20-antibody-mediated enhancement
      of IFN production might be related to its failure in lupus treatments. This work
      may provide new insights for CD20-Ab therapeutic applications. 

PMID- 23874378
TI  - A giant chelonioid turtle from the late Cretaceous of Morocco with a suction
      feeding apparatus unique among tetrapods.
AB  - BACKGROUND: Secondary adaptation to aquatic life occurred independently in
      several amniote lineages, including reptiles during the Mesozoic and mammals
      during the Cenozoic. These evolutionary shifts to aquatic environments imply
      major morphological modifications, especially of the feeding apparatus. Mesozoic
      (250-65 Myr) marine reptiles, such as ichthyosaurs, plesiosaurs, mosasaurid
      squamates, crocodiles, and turtles, exhibit a wide range of adaptations to
      aquatic feeding and a broad overlap of their tooth morphospaces with those of
      Cenozoic marine mammals. However, despite these multiple feeding behavior
      convergences, suction feeding, though being a common feeding strategy in aquatic
      vertebrates and in marine mammals in particular, has been extremely rarely
      reported for Mesozoic marine reptiles. PRINCIPAL FINDINGS: A relative of fossil
      protostegid and dermochelyoid sea turtles, Ocepechelon bouyai gen. et sp. nov. is
      a new giant chelonioid from the Late Maastrichtian (67 Myr) of Morocco exhibiting
      remarkable adaptations to marine life (among others, very dorsally and
      posteriorly located nostrils). The 70-cm-long skull of Ocepechelon not only makes
      it one of the largest marine turtles ever described, but also deviates
      significantly from typical turtle cranial morphology. It shares unique
      convergences with both syngnathid fishes (unique long tubular bony snout ending
      in a rounded and anteriorly directed mouth) and beaked whales (large size and
      elongated edentulous jaws). This striking anatomy suggests extreme adaptation for
      suction feeding unmatched among known turtles. CONCLUSION/SIGNIFICANCE: The
      feeding apparatus of Ocepechelon, a bony pipette-like snout, is unique among
      tetrapods. This new taxon exemplifies the successful systematic and ecological
      diversification of chelonioid turtles during the Late Cretaceous. This new
      evidence for a unique trophic specialization in turtles, along with the abundant
      marine vertebrate faunas associated to Ocepechelon in the Late Maastrichtian
      phosphatic beds of Morocco, further supports the hypothesis that marine life was,
      at least locally, very diversified just prior to the Cretaceous/Palaeogene (K/Pg)
      biotic crisis.

PMID- 23874379
TI  - Re-annotation of protein-coding genes in the genome of saccharomyces cerevisiae
      based on support vector machines.
AB  - The annotation of the well-studied organism, Saccharomyces cerevisiae, has been
      improving over the past decade while there are unresolved debates over the amount
      of biologically significant open reading frames (ORFs) in yeast genome. We
      revisited the total count of protein-coding genes in S. cerevisiae S288c genome
      using a theoretical approach by combining the Support Vector Machine (SVM) method
      with six widely used measurements of sequence statistical features. The accuracy
      of our method is over 99.5% in 10-fold cross-validation. Based on the annotation
      data in Saccharomyces Genome Database (SGD), we studied the coding capacity of
      all 1744 ORFs which lack experimental results and suggested that the overall
      number of chromosomal ORFs encoding proteins in yeast should be 6091 by removing
      488 spurious ORFs. The importance of the present work lies in at least two
      aspects. First, cross-validation and retrospective examination showed the
      fidelity of our method in recognizing ORFs that likely encode proteins. Second,
      we have provided a web service that can be accessed at
      http://cobi.uestc.edu.cn/services/yeast/, which enables the prediction of protein
      coding ORFs of the genus Saccharomyces with a high accuracy. 

PMID- 23874380
TI  - Estimates of excess medically attended acute respiratory infections in periods of
      seasonal and pandemic influenza in Germany from 2001/02 to 2010/11.
AB  - BACKGROUND: The number of patients seeking health care is a central indicator
      that may serve several different purposes: (1) as a proxy for the impact on the
      burden of the primary care system; (2) as a starting point to estimate the number
      of persons ill with influenza; (3) as the denominator data for the calculation of
      case fatality rate and the proportion hospitalized (severity indicators); (4) for
      economic calculations. In addition, reliable estimates of burden of disease and
      on the health care system are essential to communicate the impact of influenza to
      health care professionals, public health professionals and to the public.
      METHODOLOGY/PRINCIPAL FINDINGS: Using German syndromic surveillance data, we have
      developed a novel approach to describe the seasonal variation of medically
      attended acute respiratory infections (MAARI) and estimate the excess MAARI
      attributable to influenza. The weekly excess inside a period of influenza
      circulation is estimated as the difference between the actual MAARI and a MAARI
      baseline, which is established using a cyclic regression model for counts. As a
      result, we estimated the highest ARI burden within the last 10 years for the
      influenza season 2004/05 with an excess of 7.5 million outpatient visits (CI95%
      6.8-8.0). In contrast, the pandemic wave 2009 accounted for one third of this
      burden with an excess of 2.4 million (CI95% 1.9-2.8). Estimates can be produced
      for different age groups, different geographic regions in Germany and also in
      real time during the influenza waves.

PMID- 23874381
TI  - Selecting habitat to survive: the impact of road density on survival in a large
      carnivore.
AB  - Habitat selection studies generally assume that animals select habitat and food
      resources at multiple scales to maximise their fitness. However, animals
      sometimes prefer habitats of apparently low quality, especially when considering
      the costs associated with spatially heterogeneous human disturbance. We used
      spatial variation in human disturbance, and its consequences on lynx survival, a
      direct fitness component, to test the Hierarchical Habitat Selection hypothesis
      from a population of Eurasian lynx Lynx lynx in southern Norway. Data from 46
      lynx monitored with telemetry indicated that a high proportion of forest strongly
      reduced the risk of mortality from legal hunting at the home range scale, while
      increasing road density strongly increased such risk at the finer scale within
      the home range. We found hierarchical effects of the impact of human disturbance,
      with a higher road density at a large scale reinforcing its negative impact at a
      fine scale. Conversely, we demonstrated that lynx shifted their habitat selection
      to avoid areas with the highest road densities within their home ranges, thus
      supporting a compensatory mechanism at fine scale enabling lynx to mitigate the
      impact of large-scale disturbance. Human impact, positively associated with high
      road accessibility, was thus a stronger driver of lynx space use at a finer
      scale, with home range characteristics nevertheless constraining habitat
      selection. Our study demonstrates the truly hierarchical nature of habitat
      selection, which aims at maximising fitness by selecting against limiting factors
      at multiple spatial scales, and indicates that scale-specific heterogeneity of
      the environment is driving individual spatial behaviour, by means of trade-offs
      across spatial scales. 

PMID- 23874382
TI  - Prediction of cross-recognition of peptide-HLA A2 by Melan-A-specific cytotoxic T
      lymphocytes using three-dimensional quantitative structure-activity
      relationships.
AB  - The cross-recognition of peptides by cytotoxic T lymphocytes is a key element in
      immunology and in particular in peptide based immunotherapy. Here we develop
      three-dimensional (3D) quantitative structure-activity relationships (QSARs) to
      predict cross-recognition by Melan-A-specific cytotoxic T lymphocytes of peptides
      bound to HLA A*0201 (hereafter referred to as HLA A2). First, we predict the
      structure of a set of self- and pathogen-derived peptides bound to HLA A2 using a
      previously developed ab initio structure prediction approach [Fagerberg et al.,
      J. Mol. Biol., 521-46 (2006)]. Second, shape and electrostatic energy
      calculations are performed on a 3D grid to produce similarity matrices which are
      combined with a genetic neural network method [So et al., J. Med. Chem., 4347-59
      (1997)] to generate 3D-QSAR models. The models are extensively validated using
      several different approaches. During the model generation, the leave-one-out
      cross-validated correlation coefficient (q (2)) is used as the fitness criterion
      and all obtained models are evaluated based on their q (2) values. Moreover, the
      best model obtained for a partitioned data set is evaluated by its correlation
      coefficient (r = 0.92 for the external test set). The physical relevance of all
      models is tested using a functional dependence analysis and the robustness of the
      models obtained for the entire data set is confirmed using y-randomization.
      Finally, the validated models are tested for their utility in the setting of
      rational peptide design: their ability to discriminate between peptides that only
      contain side chain substitutions in a single secondary anchor position is
      evaluated. In addition, the predicted cross-recognition of the mono-substituted
      peptides is confirmed experimentally in chromium-release assays. These results
      underline the utility of 3D-QSARs in peptide mimetic design and suggest that the
      properties of the unbound epitope are sufficient to capture most of the
      information to determine the cross-recognition.

PMID- 23874383
TI  - The Support to Rural India's Public Education System (STRIPES) trial: a cluster
      randomised controlled trial of supplementary teaching, learning material and
      material support.
AB  - BACKGROUND: The aim of the STRIPES trial was to assess the effectiveness of
      providing supplementary, remedial teaching and learning materials (and an
      additional 'kit' of materials for girls) on a composite of language and
      mathematics test scores for children in classes two, three and four in public
      primary schools in villages in the Nagarkurnool division of Andhra Pradesh,
      India. METHODS: STRIPES was a cluster randomised trial in which 214 villages were
      allocated either to the supplementary teaching intervention (n = 107) or to serve
      as controls (n = 107). 54 of the intervention villages were further randomly
      allocated to receive additional kit for girls. The study was not blinded.
      Analysis was conducted on the intention to treat principle, allowing for
      clustering. RESULTS: Composite test scores were significantly higher in the
      intervention group (107 villages; 2364 children) than in the control group (106
      villages; 2014 children) at the end of the trial (mean difference on a percentage
      scale 15.8; 95% CI 13.1 to 18.6; p<0.001; 0.75 Standard Deviation (SD)
      difference). Composite test scores were not significantly different in the 54
      villages (614 girls) with the additional kits for girls compared to the 53
      villages (636 girls) without these kits at the end of the trial (mean difference
      on a percentage scale 0.5; 95% CI -4.34 to 5.4; p = 0.84). The cost per 0.1 SD
      increase in composite test score for intervention without kits is Rs. 382.97
      (L4.45, $7.13), and Rs.480.59 (L5.58, $8.94) for the intervention with kits.
      CONCLUSIONS: A 18 month programme of supplementary remedial teaching and learning
      materials had a substantial impact on language and mathematics scores of primary
      school students in rural Andhra Pradesh, yet providing a 'kit' of materials to
      girls in these villages did not lead to any measured additional benefit. TRIAL
      REGISTRATION: Controlled-Trials.com ISRCTN69951502.

PMID- 23874384
TI  - Genetics of callous-unemotional behavior in children.
AB  - Callous-unemotional behavior (CU) is currently under consideration as a subtyping
      index for conduct disorder diagnosis. Twin studies routinely estimate the
      heritability of CU as greater than 50%. It is now possible to estimate genetic
      influence using DNA alone from samples of unrelated individuals, not relying on
      the assumptions of the twin method. Here we use this new DNA method (implemented
      in a software package called Genome-wide Complex Trait Analysis, GCTA) for the
      first time to estimate genetic influence on CU. We also report the first genome
      wide association (GWA) study of CU as a quantitative trait. We compare these DNA
      results to those from twin analyses using the same measure and the same community
      sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA
      estimates of heritability were near zero, even though twin analysis of CU in this
      sample confirmed the high heritability of CU reported in the literature, and even
      though GCTA estimates of heritability were substantial for cognitive and
      anthropological traits in this sample. No significant associations were found in
      GWA analysis, which, like GCTA, only detects additive effects of common DNA
      variants. The phrase 'missing heritability' was coined to refer to the gap
      between variance associated with DNA variants identified in GWA studies versus
      twin study heritability. However, GCTA heritability, not twin study heritability,
      is the ceiling for GWA studies because both GCTA and GWA are limited to the
      overall additive effects of common DNA variants, whereas twin studies are not.
      This GCTA ceiling is very low for CU in our study, despite its high twin study
      heritability estimate. The gap between GCTA and twin study heritabilities will
      make it challenging to identify genes responsible for the heritability of CU. 

PMID- 23874385
TI  - Transcriptome changes associated with delayed flower senescence on transgenic
      petunia by inducing expression of etr1-1, a mutant ethylene receptor.
AB  - Flowers of ethylene-sensitive ornamental plants transformed with ethylene
      insensitive 1-1(etr1-1), a mutant ethylene receptor first isolated from
      Arabidopsis, are known to have longer shelf lives. We have generated petunia
      plants in which the etr1-1 gene was over-expressed under the control of a
      chemically-inducible promoter, which would allow expression of etr1-1 to be
      initiated at the desired time and stage of development. Here, we showed that
      transgenic plants grew and developed normally without a chemical inducer. Semi
      quantitative RT-PCR demonstrated that the abundance of transcripts of Arabidopsis
      etr1-1 gene was substantially induced in flowers with 30 MUM dexamethasone (DEX).
      Consequently, t he life of the flowers was almost doubled and the peak of
      ethylene production was delayed. We compared gene expression changes of petals
      with DEX to those without DEX at 24 h and 48 h by microarray. Our results
      indicated that transcripts of many putative genes encoding transcription factors
      were down-regulated by etr1-1 induced expression at the early stage. In addition,
      putative genes involved in gibberellin biosynthesis, response to jasmonic
      acid/gibberellins stimulus, cell wall modification, ethylene biosynthesis, and
      cell death were down-regulated associating with etr1-1 induced expression. We
      investigated time-course gene expression profiles and found two profiles which
      displayed totally opposite expression patterns under these two treatments. In
      these profiles, 'the regulation of transcription' was predominant in GO
      categories. Taking all results together, we concluded those transcription factors
      down-regulated at early stage might exert a major role in regulating the
      senescence process which were consequently characterized by cell wall
      modification and cell death. 

PMID- 23874386
TI  - Exploring the adenylation domain repertoire of nonribosomal peptide synthetases
      using an ensemble of sequence-search methods.
AB  - The introduction of two-dimension (2D) graphs and their numerical
      characterization for comparative analyses of DNA/RNA and protein sequences
      without the need of sequence alignments is an active yet recent research topic in
      bioinformatics. Here, we used a 2D artificial representation (four-color maps)
      with a simple numerical characterization through topological indices (TIs) to aid
      the discovering of remote homologous of Adenylation domains (A-domains) from the
      Nonribosomal Peptide Synthetases (NRPS) class in the proteome of the
      cyanobacteria Microcystis aeruginosa. Cyanobacteria are a rich source of
      structurally diverse oligopeptides that are predominantly synthesized by NPRS.
      Several A-domains share amino acid identities lower than 20 % being a possible
      source of remote homologous. Therefore, A-domains cannot be easily retrieved by
      BLASTp searches using a single template. To cope with the sequence diversity of
      the A-domains we have combined homology-search methods with an alignment-free
      tool that uses protein four-color-maps. TI2BioP (Topological Indices to
      BioPolymers) version 2.0, available at http://ti2biop.sourceforge.net/ allowed
      the calculation of simple TIs from the protein sequences (four-color maps). Such
      TIs were used as input predictors for the statistical estimations required to
      build the alignment-free models. We concluded that the use of graphical/numerical
      approaches in cooperation with other sequence search methods, like multi
      templates BLASTp and profile HMM, can give the most complete exploration of the
      repertoire of highly diverse protein families. 

PMID- 23874387
TI  - Transcriptional repression of Bim by a novel YY1-RelA complex is essential for
      the survival and growth of Multiple Myeloma.
AB  - Multiple Myeloma (MM) is an incurable plasma cell cancer that is caused by
      several chromosomal translocations and gene deletions. Although deregulation of
      several signaling pathways including the Nuclear Factor-Kappa B (NF-kappaB)
      pathway has been reported in MM, the molecular requirement and the crosstalk
      between NF-kappaB and its target genes in MM cell survival has been largely
      unclear. Here, we report that Yin Yang1 (YY1), a target gene for NF-kappaB, is
      hyperexpressed in most MM tumor cells obtained from human patients, exhibits
      constitutive nuclear localization, and is essential for survival of MM cells.
      Mechanistically, we report a novel YY1-RelA complex formation, which is essential
      to transcriptionally repress a proapoptotic gene Bim. In line with this,
      depletion of YY1 or RelA resulted in elevated levels of Bim and apoptosis.
      Moreover, both YY1 and RelA are recruited to the Bim promoter and are required to
      repress the Bim promoter. Importantly, depletion of YY1 or RelA almost completely
      impaired the colony forming ability of MM progenitor cells suggesting that both
      RelA and YY1 are essential for the survival and growth of MM progenitor cells.
      Moreover, depletion of either YY1 or RelA completely inhibited MM tumor growth in
      xenograft models for human myeloma. Thus, a novel RelA-YY1 transcriptional
      repression complex is an attractive drug target in MM. 

PMID- 23874388
TI  - Artificial grammar learning of melody is constrained by melodic inconsistency:
      Narmour's principles affect melodic learning.
AB  - Considerable evidence suggests that people acquire artificial grammars
      incidentally and implicitly, an indispensable capacity for the acquisition of
      music or language. However, less research has been devoted to exploring
      constraints affecting incidental learning. Within the domain of music, the extent
      to which Narmour's (1990) melodic principles affect implicit learning of melodic
      structure was experimentally explored. Extending previous research (Rohrmeier,
      Rebuschat & Cross, 2011), the identical finite-state grammar is employed having
      terminals (the alphabet) manipulated so that melodies generated systematically
      violated Narmour's principles. Results indicate that Narmour-inconsistent melodic
      materials impede implicit learning. This further constitutes a case in which
      artificial grammar learning is affected by prior knowledge or processing
      constraints. 

PMID- 23874389
TI  - Identification of critical regions in human SAMHD1 required for nuclear
      localization and Vpx-mediated degradation.
AB  - The sterile alpha motif (SAM) and HD domain-containing protein-1 (SAMHD1)
      inhibits the infection of resting CD4+ T cells and myeloid cells by human and
      related simian immunodeficiency viruses (HIV and SIV). Vpx inactivates SAMHD1 by
      promoting its proteasome-dependent degradation through an interaction with CRL4
      (DCAF1) E3 ubiquitin ligase and the C-terminal region of SAMHD1. However, the
      determinants in SAMHD1 that are required for Vpx-mediated degradation have not
      been well characterized. SAMHD1 contains a classical nuclear localization signal
      (NLS), and NLS point mutants are cytoplasmic and resistant to Vpx-mediated
      degradation. Here, we demonstrate that NLS-mutant SAMHD1 K11A can be rescued by
      wild-type SAMHD1, restoring its nuclear localization; consequently, SAMHD1 K11A
      became sensitive to Vpx-mediated degradation in the presence of wild-type SAMHD1.
      Surprisingly, deletion of N-terminal regions of SAMHD1, including the classical
      NLS, generated mutant SAMHD1 proteins that were again sensitive to Vpx-mediated
      degradation. Unlike SAMHD1 K11A, these deletion mutants could be detected in the
      nucleus. Interestingly, NLS-defective SAMHD1 could still bind to karyopherin
      beta1 and other nuclear proteins. We also determined that the linker region
      between the SAM and HD domain and the HD domain itself is important for Vpx
      mediated degradation but not Vpx interaction. Thus, SAMHD1 contains an additional
      nuclear targeting mechanism in addition to the classical NLS. Our data indicate
      that multiple regions in SAMHD1 are critical for Vpx-mediated nuclear degradation
      and that association with Vpx is not sufficient for Vpx-mediated degradation of
      SAMHD1. Since the linker region and HD domain may be involved in SAMHD1
      multimerization, our results suggest that SAMHD1 multimerization may be required
      for Vpx-mediation degradation. 

PMID- 23874390
TI  - Optimisation of potassium chloride nutrition for proper growth, physiological
      development and bioactive component production in Prunella vulgaris L.
AB  - Prunella vulgaris L. is an important medicinal plant with a variety of
      pharmacological activities, but limited information is available about its
      response to potassium chloride (KCl) supplementation. P. vulgaris seedlings were
      cultured in media with four different KCl levels (0, 1.00, 6.00 and 40.00 mM).
      Characteristics relating to the growth, foliar potassium, water and chlorophyll
      content, photosynthesis, transpiration, nitrogen metabolism, bioactive
      constituent concentrations and yield were determined after three months. The
      appropriate KCl concentration was 6.00 mM to result in the highest values for dry
      weight, shoot height, spica and root weight, spica length and number in P.
      vulgaris. The optimum KCl concentration resulted in a maximum net photosynthetic
      rate (Pn) that could be associated with the highest chlorophyll content and fully
      open stomata conductance. A supply of surplus KCl resulted in a higher
      concentration of foliar potassium and negatively correlated with the biomass.
      Plants that were treated with the appropriate KCl level showed a greater capacity
      for nitrate assimilation. The Pn was significantly and positively correlated with
      nitrate reductase (NR) and glutamine synthetase (GS) activities and was
      positively correlated with leaf-soluble protein and free amino acid (FAA)
      contents. Both KCl starvation (0 mM) and high KCl (40.00 mM) led to water loss
      through a high transpiration rate and low water absorption, respectively, and
      resulted in increased concentrations of ursolic acid (UA), oleanolic acid (OA)
      and flavonoids, with the exception of rosmarinic acid (RA). Moreover, the optimum
      concentration of KCl significantly increased the yields of RA, UA, OA and
      flavonoids. Our findings suggested that significantly higher plant biomass;
      chlorophyll content; Pn; stronger nitrogen anabolism; lower RA, UA, OA and
      flavonoid accumulation; and greater RA, UA, OA and flavonoid yields in P.
      vulgaris could be expected in the presence of the appropriate KCl concentration
      (6.00 mM). 

PMID- 23874391
TI  - Low molecular weight heparin relieves experimental colitis in mice by
      downregulating IL-1beta and inhibiting syndecan-1 shedding in the intestinal
      mucosa.
AB  - Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but
      its effect on inflammation in colitis remains unclear. This study aimed to
      evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced
      colitis in mice, in which acute colitis progresses to chronic colitis, and to
      explore the potential mechanism involved in this process. C57BL/6 mice were
      randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease
      activity was scored by a disease activity index (DAI). Histological changes were
      evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1,
      interleukin (IL)-1beta, and IL-10 were determined by quantitative reverse
      transcription polymerase chain reaction. Protein expression of syndecan-1 was
      detected by immunohistochemistry. The serum syndecan-1 level was examined by a
      dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced
      by DSS administration in mice. Colon destruction with the appearance of crypt
      damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS
      administration, which was greatly relieved by the treatment of LMWH. LMWH
      upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum
      syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS
      group). In addition, LMWH significantly decreased the expression of both IL-1beta
      and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic
      effects on colitis by downregulating inflammatory cytokines and inhibiting
      syndecan-1 shedding in the intestinal mucosa. 

PMID- 23874392
TI  - Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of
      GATA3.
AB  - The accumulated uremic toxins inhibit the expression of various renal
      transporters and this inhibition may further reduce renal function and
      subsequently cause the accumulation of uremic toxins. However, the precise
      mechanism of the nephrotoxicity of uremic toxins on renal transport has been
      poorly understood. Here we report that indoxyl sulfate, one of the potent uremic
      toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1
      expression through a transcription factor GATA3. The promoter region of SLCO4C1
      gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and
      subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly
      reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression
      vice versa. Administration of indoxyl sulfate in rats reduced renal expression of
      slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the
      preferable substrates of slco4c1, was significantly increased without changing
      plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral
      adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and
      conversely increased the expression of slco4c1, following the reduction of plasma
      level of guanidinosuccinate. These data suggest that the removal of indoxyl
      sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated
      renal excretion of uremic toxins in CKD. 

PMID- 23874393
TI  - Computational models for prediction of yeast strain potential for winemaking from
      phenotypic profiles.
AB  - Saccharomyces cerevisiae strains from diverse natural habitats harbour a vast
      amount of phenotypic diversity, driven by interactions between yeast and the
      respective environment. In grape juice fermentations, strains are exposed to a
      wide array of biotic and abiotic stressors, which may lead to strain selection
      and generate naturally arising strain diversity. Certain phenotypes are of
      particular interest for the winemaking industry and could be identified by
      screening of large number of different strains. The objective of the present work
      was to use data mining approaches to identify those phenotypic tests that are
      most useful to predict a strain's potential for winemaking. We have constituted a
      S. cerevisiae collection comprising 172 strains of worldwide geographical origins
      or technological applications. Their phenotype was screened by considering 30
      physiological traits that are important from an oenological point of view. Growth
      in the presence of potassium bisulphite, growth at 40  degrees C, and resistance
      to ethanol were mostly contributing to strain variability, as shown by the
      principal component analysis. In the hierarchical clustering of phenotypic
      profiles the strains isolated from the same wines and vineyards were scattered
      throughout all clusters, whereas commercial winemaking strains tended to co
      cluster. Mann-Whitney test revealed significant associations between phenotypic
      results and strain's technological application or origin. Naive Bayesian
      classifier identified 3 of the 30 phenotypic tests of growth in iprodion (0.05
      mg/mL), cycloheximide (0.1 ug/mL) and potassium bisulphite (150 mg/mL) that
      provided most information for the assignment of a strain to the group of
      commercial strains. The probability of a strain to be assigned to this group was
      27% using the entire phenotypic profile and increased to 95%, when only results
      from the three tests were considered. Results show the usefulness of
      computational approaches to simplify strain selection procedures.

PMID- 23874394
TI  - LifeMap DiscoveryTM: the embryonic development, stem cells, and regenerative
      medicine research portal.
AB  - LifeMap DiscoveryTM provides investigators with an integrated database of
      embryonic development, stem cell biology and regenerative medicine. The hand
      curated reconstruction of cell ontology with stem cell biology; including
      molecular, cellular, anatomical and disease-related information, provides
      efficient and easy-to-use, searchable research tools. The database collates in
      vivo and in vitro gene expression and guides translation from in vitro data to
      the clinical utility, and thus can be utilized as a powerful tool for research
      and discovery in stem cell biology, developmental biology, disease mechanisms and
      therapeutic discovery. LifeMap Discovery is freely available to academic
      nonprofit institutions at http://discovery.lifemapsc.com. 

PMID- 23874395
TI  - Functional contribution of the transcription factor ATF4 to the pathogenesis of
      amyotrophic lateral sclerosis.
AB  - Endoplasmic reticulum (ER) stress represents an early pathological event in
      amyotrophic lateral sclerosis (ALS). ATF4 is a key ER stress transcription factor
      that plays a role in both adaptation to stress and the activation of apoptosis.
      Here we investigated the contribution of ATF4 to ALS. ATF4 deficiency reduced the
      rate of birth of SOD1(G86R) transgenic mice. The fraction of ATF4(-/-)-SOD1(G85R)
      transgenic mice that were born are more resistant to develop ALS, leading to
      delayed disease onset and prolonged life span. ATF4 deficiency completely
      attenuated the induction of pro-apoptotic genes, including BIM and CHOP, and also
      led to quantitative changes in the ER protein homeostasis network. Unexpectedly,
      ATF4 deficiency enhanced mutant SOD1 aggregation at the end stage of the disease.
      Studies in the motoneuron cell line NSC34 demonstrated that knocking down ATF4
      enhances mutant SOD1 aggregation possibly due to alteration in the redox status
      of the cell. Our results support a functional role of ATF4 in ALS, offering a
      novel target for disease intervention. 

PMID- 23874396
TI  - TdIF1 recognizes a specific DNA sequence through its Helix-Turn-Helix and AT-hook
      motifs to regulate gene transcription.
AB  - TdIF1 was originally identified as a protein that directly binds to DNA
      polymerase TdT. TdIF1 is also thought to function in transcription regulation,
      because it binds directly to the transcriptional factor TReP-132, and to histone
      deacetylases HDAC1 and HDAC2. Here we show that TdIF1 recognizes a specific DNA
      sequence and regulates gene transcription. By constructing TdIF1 mutants, we
      identify amino acid residues essential for its interaction with DNA. An in vitro
      DNA selection assay, SELEX, reveals that TdIF1 preferentially binds to the
      sequence 5'-GNTGCATG-3' following an AT-tract, through its Helix-Turn-Helix and
      AT-hook motifs. We show that four repeats of this recognition sequence allow
      TdIF1 to regulate gene transcription in a plasmid-based luciferase reporter
      assay. We demonstrate that TdIF1 associates with the RAB20 promoter, and RAB20
      gene transcription is reduced in TdIF1-knocked-down cells, suggesting that TdIF1
      stimulates RAB20 gene transcription. 

PMID- 23874397
TI  - Human folliculin delays cell cycle progression through late S and G2/M-phases:
      effect of phosphorylation and tumor associated mutations.
AB  - The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human
      Folliculin gene (FLCN), and is characterized by clinical features including
      fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and
      genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human
      cell line UOK257, derived from the renal cell carcinoma of a patient with a
      germline mutation in the FLCN gene, harbors a truncated version of the FLCN
      protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays
      cell cycle progression, due to a slower progression through the late S and G2/M
      phases. Similarly, Flcn (-/-) mouse embryonic fibroblasts progress more rapidly
      through the cell cycle than wild type controls (Flcn (flox/flox)). The
      reintroduction of tumor-associated FLCN mutants (FLCN DeltaF157, FLCN 1-469 or
      FLCN K508R) fails to delay cell cycle progression in UOK257 cells. Additionally,
      FLCN phosphorylation (on Serines 62 and 73) fluctuates throughout the cell cycle
      and peaks during the G2/M phase in cells treated with nocodazole. In keeping with
      this observation, the reintroduction of a FLCN phosphomimetic mutant into the
      UOK257 cell line results in faster progression through the cell cycle compared to
      those expressing the wild type FLCN protein. These findings suggest that the
      tumor suppression function of FLCN may be linked to its impact on the cell cycle
      and that FLCN phosphorylation is important for this activity. Additionally, these
      observations describe a novel in vitro assay for testing the functional
      significance of FLCN mutations and/or genetic polymorphisms. 

PMID- 23874398
TI  - Muscular weakness in individuals with HIV associated with a disorganization of
      the cortico-spinal tract: a multi-modal MRI investigation.
AB  - Motor impairment is highly prevalent in HIV-infected patients. Here, we assess
      associations between peripheral muscular deficits as evaluated by the 5 sit-to
      stand test (5STS) and structural integrity of the motor system at a central
      level. Eighty-six HIV-infected patients receiving combination antiretroviral
      therapy and with no major cerebral events, underwent an MRI scan and the 5STS.
      Out of 86 participants, forty presented a score greater than two standard
      deviations above mean normative scores calculated for the 5STS and were therefore
      considered as motor-impaired. MRI-structural cerebral parameters were compared to
      the unimpaired participants. Fractional Anisotropy (FA), Axial Diffusivity (AD)
      and Radial Diffusivity (RD), reflecting microstructural integrity, were extracted
      from Diffusion-Tensor MRI. Global and regional cerebral volumes or thicknesses
      were extracted from 3D-T1 morphological MRI. Whereas the two groups did not
      differ for any HIV variables, voxel-wise analysis revealed that motor-impaired
      participants present low FA values in various cortico-motor tracts and low AD in
      left cortico-spinal tract. However, they did not present reduced volumes or
      thicknesses of the precentral cortices compared to unimpaired participants. The
      absence of alterations in cortical regions holding motor-neurons might argue
      against neurodegenerative process as an explanation of White Matter (WM)
      disorganization. 

PMID- 23874399
TI  - Gonadotrope-specific expression and regulation of ovine follicle stimulating
      hormone Beta: transgenic and adenoviral approaches using primary murine
      gonadotropes.
AB  - The beta subunit of follicle stimulating hormone (FSHB) is expressed specifically
      in pituitary gonadotropes in vertebrates. Transgenic mouse studies have shown
      that enhancers in the proximal promoter between -172/-1 bp of the ovine FSHB gene
      are required for gonadotrope expression of ovine FSHB. These enhancers are
      associated with regulation by activins and gonadotropin releasing hormone (GnRH).
      Additional distal promoter sequence between -4741/-750 bp is also required for
      expression. New transgenic studies presented here focus on this distal region and
      narrow it to 1116 bp between -1866/-750 bp. In addition, adenoviral constructs
      were produced to identify these critical distal sequences using purified primary
      mouse gonadotropes as an in vitro model system. The adenoviral constructs
      contained -2871 bp, -750 bp or -232 bp of the ovine FSHB promoter. They all
      showed gonadotrope-specific regulation since they were induced only in purified
      primary gonadotropes by activin A (50 ng/ml) and inhibited by GnRH (100 nM) in
      the presence of activin (except -232FSHBLuc). However, basal expression of all
      three viral constructs (in the presence of follistatin to block cellular
      induction by activin) was relatively high in pituitary non-gonadotropes as well
      as gonadotropes. Thus, gonadotrope-specific regulation associated with the
      proximal promoter was observed as expected, but the model was blind to distal
      promoter elements between -2871/-750 necessary for gonadotrope-specific
      expression of ovine FSHB in vivo. The new adenoviral-based in vitro technique did
      detect, however, a novel GnRH response element between -750 bp and -232 bp of the
      ovine FSHB promoter. We conclude that adenoviral-based studies in primary
      gonadotropes can adequately recognize regulatory elements on the ovine FSHB
      promoter associated with gonadotrope-specific regulation/expression, but that
      more physiologically based techniques, such as transgenic studies, will be needed
      to identify sequences between -1866/-750 bp of the ovine FSHB promoter that are
      also required for tissue/cell specific expression in vivo. 

PMID- 23874400
TI  - The PyRosetta Toolkit: a graphical user interface for the Rosetta software suite.
AB  - The Rosetta Molecular Modeling suite is a command-line-only collection of
      applications that enable high-resolution modeling and design of proteins and
      other molecules. Although extremely useful, Rosetta can be difficult to learn for
      scientists with little computational or programming experience. To that end, we
      have created a Graphical User Interface (GUI) for Rosetta, called the PyRosetta
      Toolkit, for creating and running protocols in Rosetta for common molecular
      modeling and protein design tasks and for analyzing the results of Rosetta
      calculations. The program is highly extensible so that developers can add new
      protocols and analysis tools to the PyRosetta Toolkit GUI. 

PMID- 23874402
TI  - GNPs-CS/KGM as hemostatic first aid wound dressing with antibiotic effect: in
      vitro and in vivo study.
AB  - Ideal wound dressing materials should create a good healing environment, with
      immediate hemostatic effects and antimicrobial activity. In this study,
      chitosan/konjac glucomannan (CS/KGM) films embedded with gentamicin-loaded
      poly(dex-GMA/AAc) nanoparticles (giving GNP-CS/KGM films) were prepared as novel
      wound dressings. The results revealed that the modified CS/KGM films could be
      used as effective wound dressings and had significant hemostatic effects. With
      their microporous structure, the films could effectively absorb water from blood
      and trap blood cells. The gentamicinloaded poly(dex-GMA/AAc) nanoparticles (GNPs)
      also further promoted blood clotting, with their favorable water uptake capacity.
      Thus, the GNP-CS/KGM films had wound healing and synergistic effects that helped
      to stop bleeding from injuries, and also showed good antibiotic abilities by
      addition of gentamicin to the NPs. These GNPCS/KGM films can be considered as
      promising novel biodegradable and biocompatible wound dressings with hemostatic
      capabilities and antibiotic effects for treatment of external bleeding injuries. 

PMID- 23874401
TI  - Functional polymorphisms in the CYP2C19 gene contribute to digestive system
      cancer risk: evidence from 11,042 subjects.
AB  - BACKGROUND: CYP2C19 belongs to the cytochrome P450 superfamily of enzymes
      involved in activating and detoxifying many carcinogens and endogenous compounds,
      which has attracted considerable attention as a candidate gene for digestive
      system cancer. CYP2C19 has two main point mutation sites (CYP2C19*2, CYP2C19*3)
      leading to poor metabolizer (PM) phenotype. In the past decade, the relationship
      between CYP2C19 polymorphism and digestive system cancer has been reported in
      various ethnic groups; however, these studies have yielded contradictory results.
      METHODS: To clarify this inconsistency, we performed this meta-analysis.
      Databases including Pubmed, EMBASE, Web of Science and China National Knowledge
      Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were used to assess the strength of
      association. RESULTS: In total, 18 studies with 4,414 cases and 6,628 controls
      were included. Overall, significantly elevated digestive system cancer risk was
      associated CYP2C19 PM with OR of 1.66 (95%CI: 1.31-2.10, P<10(-5)) when all
      studies were pooled into the meta-analysis. There was strong evidence of
      heterogeneity (P = 0.006), which largely disappeared after stratification by
      cancer type. In the stratified analyses according to cancer type, ethnicity,
      control source and sample size, significantly increased risks were found.
      CONCLUSIONS: In summary, our meta-analysis suggested that the PM phenotype caused
      by the variation on CYP2C19 gene is associated with increased risk of digestive
      system cancer, especially in East Asians.

PMID- 23874403
TI  - Diffusion tensor tractography versus volumetric imaging in the diagnosis of
      behavioral variant frontotemporal dementia.
AB  - MRI diffusion tensor imaging (DTI) studies of white matter integrity in
      behavioral variant frontotemporal dementia have consistently shown involvement of
      frontal and temporal white matter, corresponding to regional loss of cortical
      volume. Volumetric imaging has a suboptimal sensitivity as a diagnostic tool and
      thus we wanted to explore if DTI is a better method to discriminate patients and
      controls than volumetric imaging. We examined the anterior cingulum bundle in 14
      patients with behavioral variant frontotemporal dementia and 22 healthy controls
      using deterministic manual diffusion tensor tractography, and compared DTI
      parameters with two measures of cortical atrophy, VBM and cortical thickness, of
      the anterior cingulate cortex (ACC). Statistically significant changes between
      patients and controls were detected in all DTI parameters, with large effect
      sizes. ROC-AUC was for the best DTI parameters: 0.92 (fractional anisotropy) to
      0.97 (radial diffusivity), 0.82 for the best cortical parameter, VBM of the ACC.
      Results from the AUC were confirmed with binary logistic regression analysis
      including demographic variables, but only for fractional anisotropy and mean
      diffusivity. Ability to classify patient/nonpatient status was significantly
      better for mean diffusivity vs. VBM (p=0.031), and borderline significant for
      fractional anisotropy vs. VBM (p=0.062). The results indicate that DTI could
      offer advantages in comparison with the assessment of cortical volume in
      differentiating patients with behavioral variant frontotemporal dementia and
      controls. 

PMID- 23874404
TI  - Tethered domains and flexible regions in tRNase Z(L), the long form of tRNase Z.
AB  - tRNase Z, a member of the metallo-beta-lactamase family, endonucleolytically
      removes the pre-tRNA 3' trailer in a step central to tRNA maturation. The short
      form (tRNase Z(S)) is the only one found in bacteria and archaebacteria and is
      also present in some eukaryotes. The homologous long form (tRNase Z(L)),
      exclusively found in eukaryotes, consists of related amino- and carboxy-domains,
      suggesting that tRNase Z(L) arose from a tandem duplication of tRNase Z(S)
      followed by interdependent divergence of the domains. X-ray crystallographic
      structures of tRNase Z(S) reveal a flexible arm (FA) extruded from the body of
      tRNase Z remote from the active site that binds tRNA far from the scissile bond.
      No tRNase Z(L) structures have been solved; alternative biophysical studies are
      therefore needed to illuminate its functional characteristics. Structural
      analyses of tRNase Z(L) performed by limited proteolysis, two dimensional gel
      electrophoresis and mass spectrometry establish stability of the amino and
      carboxy domains and flexibility of the FA and inter-domain tether, with
      implications for tRNase Z(L) function. 

PMID- 23874406
TI  - A novel single virus infection system reveals that influenza virus preferentially
      infects cells in g1 phase.
AB  - BACKGROUND: Influenza virus attaches to sialic acid residues on the surface of
      host cells via the hemagglutinin (HA), a glycoprotein expressed on the viral
      envelope, and enters into the cytoplasm by receptor-mediated endocytosis. The
      viral genome is released and transported in to the nucleus, where transcription
      and replication take place. However, cellular factors affecting the influenza
      virus infection such as the cell cycle remain uncharacterized. METHODS/RESULTS:
      To resolve the influence of cell cycle on influenza virus infection, we performed
      a single-virus infection analysis using optical tweezers. Using this newly
      developed single-virus infection system, the fluorescence-labeled influenza virus
      was trapped on a microchip using a laser (1064 nm) at 0.6 W, transported, and
      released onto individual H292 human lung epithelial cells. Interestingly, the
      influenza virus attached selectively to cells in the G1-phase. To clarify the
      molecular differences between cells in G1- and S/G2/M-phase, we performed several
      physical and chemical assays. Results indicated that: 1) the membranes of cells
      in G1-phase contained greater amounts of sialic acids (glycoproteins) than the
      membranes of cells in S/G2/M-phase; 2) the membrane stiffness of cells in S/G2/M
      phase is more rigid than those in G1-phase by measurement using optical tweezers;
      and 3) S/G2/M-phase cells contained higher content of Gb3, Gb4 and GlcCer than G1
      phase cells by an assay for lipid composition. CONCLUSIONS: A novel single-virus
      infection system was developed to characterize the difference in influenza virus
      susceptibility between G1- and S/G2/M-phase cells. Differences in virus binding
      specificity were associated with alterations in the lipid composition, sialic
      acid content, and membrane stiffness. This single-virus infection system will be
      useful for studying the infection mechanisms of other viruses.

PMID- 23874405
TI  - New aspects of an old drug--diclofenac targets MYC and glucose metabolism in
      tumor cells.
AB  - Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent
      anticancer effects. Up to now these effects were mainly attributed to its
      classical role as COX-inhibitor. Here we show novel COX-independent effects of
      diclofenac. Diclofenac significantly diminished MYC expression and modulated
      glucose metabolism resulting in impaired melanoma, leukemia, and carcinoma cell
      line proliferation in vitro and reduced melanoma growth in vivo. In contrast, the
      non-selective COX inhibitor aspirin and the COX-2 specific inhibitor NS-398 had
      no effect on MYC expression and glucose metabolism. Diclofenac significantly
      decreased glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and
      monocarboxylate transporter 1 (MCT1) gene expression in line with a decrease in
      glucose uptake and lactate secretion. A significant intracellular accumulation of
      lactate by diclofenac preceded the observed effect on gene expression, suggesting
      a direct inhibitory effect of diclofenac on lactate efflux. While intracellular
      lactate accumulation impairs cellular proliferation and gene expression, it does
      not inhibit MYC expression as evidenced by the lack of MYC regulation by the MCT
      inhibitor alpha-cyano-4-hydroxycinnamic acid. Finally, in a cell line with a
      tetracycline-regulated c-MYC gene, diclofenac decreased proliferation both in the
      presence and absence of c-MYC. Thus, diclofenac targets tumor cell proliferation
      via two mechanisms, that is inhibition of MYC and lactate transport. Based on
      these results, diclofenac holds potential as a clinically applicable MYC and
      glycolysis inhibitor supporting established tumor therapies. 

PMID- 23874408
TI  - Multi-level determinants of parasitic fly infection in forest passerines.
AB  - The study of myiasis is important because they may cause problems to the
      livestock industry, public health, or wildlife conservation. The ecology of
      parasitic dipterans that cause myiasis is singular, as they actively seek their
      hosts over relatively long distances. However, studies that address the
      determinants of myiasis dynamics are very scarce. The genus Philornis include
      species that may be excellent models to study myiasis ecology, as they
      exclusively parasitize bird nestlings, which stay in their nests until they are
      fully fledged, and larvae remain at the point of entry until the parasitic stage
      is over, thus allowing the collection of sequential individual-level infection
      data from virtually all the hosts present at a particular area. Here we offer a
      stratified multi-level analysis of longitudinal data of Philornis torquans
      parasitism in replicated forest bird communities of central Argentina. Using
      Generalized Linear Models and Generalized Linear Mixed Models and an information
      theory approach for model selection, we conducted four groups of analyses, each
      with a different study unit, the individual, the brood, the community at a given
      week, and the community at a given year. The response variable was larval
      abundance per nestling or mean abundance per nestling. At each level, models
      included the variables of interest of that particular level, and also potential
      confounders and effect modifiers of higher levels. We found associations of large
      magnitude at all levels, but only few variables truly governed the dynamics of
      this parasite. At the individual level, the infection was determined by the
      species and the age of the host. The main driver of parasite abundance at the
      microhabitat level was the average height of the forest, and at the community
      level, the density of hosts and prior rainfall. This multi-level approach
      contributed to a better understanding of the ecology of myiasis. 

PMID- 23874407
TI  - The DSF quorum sensing system controls the positive influence of Stenotrophomonas
      maltophilia on plants.
AB  - The interaction of the Gram-negative bacterium Stenotrophomonas maltophilia with
      eukaryotes can improve overall plant growth and health, but can also cause
      opportunistic infections in humans. While the quorum sensing molecule DSF
      (diffusible signal factor) is responsible for the regulation of phenotypes in
      pathogenic Stenotrophomonas, up until now, no beneficial effects were reported to
      be controlled by it. Our objective was to study the function of DSF in the plant
      growth promoting model strain S. maltophilia R551-3 using functional and
      transcriptomic analyses. For this purpose, we compared the wild-type strain with
      a mutant deficient in the rpfF (regulation of pathogenicity factors) gene that is
      essential for the synthesis of DSF. Oilseed rape seeds treated with the wild-type
      strain showed a statistically significant increase in germination rate compared
      with those treated with the rpfF mutant. Similarly, the wild-type strain
      exhibited better plant growth promotion and a greater efficiency in colonizing
      oilseed rape compared to the mutant strain. Moreover, only the wild-type was
      capable of forming structured cell aggregates both in vitro and in the
      rhizosphere, a characteristic mediated by DSF. Gene transcription analyses showed
      that numerous genes known to play a role in plant colonization (e.g. chemotaxis,
      cell motility, biofilm formation, multidrug efflux pumps) are controlled by the
      rpf/DSF system in S. maltophilia. In addition, we detected new potential
      functions of spermidine, primarily for both growth promotion and stress
      protection. Overall, our results showed a correspondence between the regulation
      of DSF and the positive interaction effect with the plant host. 

PMID- 23874409
TI  - Skull ecomorphology of megaherbivorous dinosaurs from the dinosaur park formation
      (upper campanian) of Alberta, Canada.
AB  - Megaherbivorous dinosaur coexistence on the Late Cretaceous island continent of
      Laramidia has long puzzled researchers, owing to the mystery of how so many large
      herbivores (6-8 sympatric species, in many instances) could coexist on such a
      small (4-7 million km(2)) landmass. Various explanations have been put forth, one
      of which-dietary niche partitioning-forms the focus of this study. Here, we apply
      traditional morphometric methods to the skulls of megaherbivorous dinosaurs from
      the Dinosaur Park Formation (upper Campanian) of Alberta to infer the
      ecomorphology of these animals and to test the niche partitioning hypothesis. We
      find evidence for niche partitioning not only among contemporaneous ankylosaurs,
      ceratopsids, and hadrosaurids, but also within these clades at the family and
      subfamily levels. Consubfamilial ceratopsids and hadrosaurids differ
      insignificantly in their inferred ecomorphologies, which may explain why they
      rarely overlap stratigraphically: interspecific competition prevented their
      coexistence. 

PMID- 23874410
TI  - Unique mechanism of the interaction between honey bee toxin TPNQ and rKir1.1
      potassium channel explored by computational simulations: insights into the
      relative insensitivity of channel towards animal toxins.
AB  - BACKGROUND: The 21-residue compact tertiapin-Q (TPNQ) toxin, a derivative of
      honey bee toxin tertiapin (TPN), is a potent blocker of inward-rectifier K(+)
      channel subtype, rat Kir1.1 (rKir1.1) channel, and their interaction mechanism
      remains unclear. PRINCIPAL FINDINGS: Based on the flexible feature of potassium
      channel turrets, a good starting rKir1.1 channel structure was modeled for the
      accessibility of rKir1.1 channel turrets to TPNQ toxin. In combination with
      experimental alanine scanning mutagenesis data, computational approaches were
      further used to obtain a reasonable TPNQ toxin-rKir1.1 channel complex structure,
      which was completely different from the known binding modes between animal toxins
      and potassium channels. TPNQ toxin mainly adopted its helical domain as the
      channel-interacting surface together with His12 as the pore-blocking residue. The
      important Gln13 residue mainly contacted channel residues near the selectivity
      filter, and Lys20 residue was surrounded by a polar "groove" formed by Arg118,
      Thr119, Glu123, and Asn124 in the channel turret. On the other hand, four turrets
      of rKir1.1 channel gathered to form a narrow pore entryway for TPNQ toxin
      recognition. The Phe146 and Phe148 residues in the channel pore region formed
      strong hydrophobic protrusions, and produced dominant nonpolar interactions with
      toxin residues. These specific structure features of rKir1.1 channel vestibule
      well matched the binding of potent TPNQ toxin, and likely restricted the binding
      of the classical animal toxins. CONCLUSIONS/SIGNIFICANCE: The TPNQ toxin-rKir1.1
      channel complex structure not only revealed their unique interaction mechanism,
      but also would highlight the diverse animal toxin-potassium channel interactions,
      and elucidate the relative insensitivity of rKir1.1 channel towards animal
      toxins.

PMID- 23874412
TI  - Developing a scorecard to assess global progress in scaling up diarrhea control
      tools: a qualitative study of academic leaders and implementers.
AB  - BACKGROUND: In 2010, diarrhea caused 0.75 million child deaths, accounting for
      nearly 12% of all under-five mortality worldwide. Many evidence-based
      interventions can reduce diarrhea mortality, including oral rehydration solution
      (ORS), zinc, and improved sanitation. Yet global coverage levels of such
      interventions remain low. A new scorecard of diarrhea control, showing how
      different countries are performing in their control efforts, could draw greater
      attention to the low coverage levels of proven interventions. METHODS: We
      conducted in-depth qualitative interviews with 21 experts, purposively sampled
      for their relevant academic or implementation expertise, to explore their views
      on (a) the value of a scorecard of global diarrhea control and (b) which
      indicators should be included in such a scorecard. We then conducted a ranking
      exercise in which we compiled a list of all 49 indicators suggested by the
      experts, sent the list to the 21 experts, and asked them to choose 10 indicators
      that they would include and 10 that they would exclude from such a scorecard.
      Finally, we created a "prototype" scorecard based on the 9 highest-ranked
      indicators. RESULTS: Key themes that emerged from coding the interview
      transcripts were: a scorecard could facilitate country comparisons; it could help
      to identify best practices, set priorities, and spur donor action; and it could
      help with goal-setting and accountability in diarrhea control. The nine highest
      ranking indicators, in descending order, were ORS coverage, rotavirus vaccine
      coverage, zinc coverage, diarrhea-specific mortality rate, diarrhea prevalence,
      proportion of population with access to improved sanitation, proportion with
      access to improved drinking water, exclusive breastfeeding coverage, and measles
      vaccine coverage. CONCLUSION: A new scorecard of global diarrhea control could
      help track progress, focus prevention and treatment efforts on the most effective
      interventions, establish transparency and accountability, and alert donors and
      ministries of health to inadequacies in diarrhea control efforts.

PMID- 23874411
TI  - Cholesterol-secreting and statin-responsive hepatocytes from human ES and iPS
      cells to model hepatic involvement in cardiovascular health.
AB  - Hepatocytes play a central and crucial role in cholesterol and lipid homeostasis,
      and their proper function is of key importance for cardiovascular health. In
      particular, hepatocytes (especially periportal hepatocytes) endogenously
      synthesize large amounts of cholesterol and secrete it into circulating blood via
      apolipoprotein particles. Cholesterol-secreting hepatocytes are also the
      clinically-relevant cells targeted by statin treatment in vivo. The study of
      cholesterol homeostasis is largely restricted to the use of animal models and
      immortalized cell lines that do not recapitulate those key aspects of normal
      human hepatocyte function that result from genetic variation of individuals
      within a population. Hepatocyte-like cells (HLCs) derived from human embryonic
      and induced pluripotent stem cells can provide a cell culture model for the study
      of cholesterol homeostasis, dyslipidemias, the action of statins and other
      pharmaceuticals important for cardiovascular health. We have analyzed expression
      of core components for cholesterol homeostasis in untreated human iPS cells and
      in response to pravastatin. Here we show the production of differentiated cells
      resembling periportal hepatocytes from human pluripotent stem cells. These cells
      express a broad range of apolipoproteins required for secretion and elimination
      of serum cholesterol, actively secrete cholesterol into the medium, and respond
      functionally to statin treatment by reduced cholesterol secretion. Our research
      shows that HLCs derived from human pluripotent cells provide a robust cell
      culture system for the investigation of the hepatic contribution to human
      cholesterol homeostasis at both cellular and molecular levels. Importantly, it
      permits for the first time to also functionally assess the impact of genetic
      polymorphisms on cholesterol homeostasis. Finally, the system will also be useful
      for mechanistic studies of heritable dyslipidemias, drug discovery, and
      investigation of modes of action of cholesterol-modulatory drugs. 

PMID- 23874413
TI  - Crucial optimization of translational components towards efficient incorporation
      of unnatural amino acids into proteins in mammalian cells.
AB  - The ability to site-specifically incorporate unnatural amino acids (UAAs) into
      proteins is a powerful tool in protein engineering. While dozens of UAAs have
      been successfully introduced into proteins expressed by Escherichia coli cells,
      it has been much more challenging to create tRNA and tRNA-Synthetase pairs that
      enable UAAs incorporation, for use in mammalian systems. By altering the
      orthogonality properties of existing unnatural pairs, previously evolved pairs
      for use in E. coli could be used in mammalian cells. This would bypass the
      cumbersome step of having to evolve mutant synthetases and would allow for the
      rapid development of new mammalian pairs. A major limitation to the amount of UAA
      containing proteins that can be expressed in the cell is the availability of UAA
      charged orthogonal suppressor tRNA. By using a natural mammalian tRNA promoter,
      the amount of functional suppressor tRNA can be greatly increased. Furthermore,
      increasing recognition of the suppressor tRNA by the mutant synthetase will
      ultimately lead to the appearance of more UAA-charged tRNA. 

PMID- 23874414
TI  - Genomic instability in liver cells caused by an LPS-induced bystander-like
      effect.
AB  - Bacterial infection has been linked to carcinogenesis, however, there is lack of
      knowledge of molecular mechanisms that associate infection with the development
      of cancer. We analyzed possible effects of the consumption of heat-killed E. coli
      O157:H7 cells or its cellular components, DNA, RNA, protein or
      lipopolysaccharides (LPS) on gene expression in naive liver cells. Four week old
      mice were provided water supplemented with whole heat-killed bacteria or
      bacterial components for a two week period. One group of animals was sacrificed
      immediately, whereas another group was allowed to consume uncontaminated tap
      water for an additional two weeks, and liver samples were collected, post mortem.
      Liver cells responded to exposure of whole heat-killed bacteria and LPS with
      alteration in gammaH2AX levels and levels of proteins involved in proliferation,
      DNA methylation (MeCP2, DNMT1, DNMT3A and 3B) or DNA repair (APE1 and KU70) as
      well as with changes in the expression of genes involved in stress response, cell
      cycle control and bile acid biosynthesis. Other bacterial components analysed in
      this study did not lead to any significant changes in the tested molecular
      parameters. This study suggests that lipopolysaccharides are a major component of
      Gram-negative bacteria that induce molecular changes within naive cells of the
      host. 

PMID- 23874415
TI  - Thresher sharks use tail-slaps as a hunting strategy.
AB  - The hunting strategies of pelagic thresher sharks (Alopias pelagicus) were
      investigated at Pescador Island in the Philippines. It has long been suspected
      that thresher sharks hunt with their scythe-like tails but the kinematics
      associated with the behaviour in the wild are poorly understood. From 61
      observations recorded by handheld underwater video camera between June and
      October 2010, 25 thresher shark shunting events were analysed. Thresher sharks
      employed tail-slaps to debilitate sardines at all times of day. Hunting events
      comprised preparation, strike, wind-down recovery and prey item collection
      phases, which occurred sequentially. Preparation phases were significantly longer
      than the others, presumably to enable a shark to windup a tail-slap. Tail-slaps
      were initiated by an adduction of the pectoral fins, a manoeuvre that changed a
      thresher shark's pitch promoting its posterior region to lift rapidly, and stall
      its approach. Tail-slaps occurred with such force that they may have caused
      dissolved gas to diffuse out of the water column forming bubbles. Thresher sharks
      were able to consume more than one sardine at a time, suggesting that tail
      slapping is an effective foraging strategy for hunting schooling prey. Pelagic
      thresher sharks appear to pursue sardines opportunistically by day and night,
      which may make them vulnerable to fisheries. Alopiids possess specialist pectoral
      and caudal fins that are likely to have evolved, at least in part, for tail
      slapping. The evidence is now clear; thresher sharks really do hunt with their
      tails. 

PMID- 23874416
TI  - Neglecting the left side of a city square but not the left side of its clock:
      prevalence and characteristics of representational neglect.
AB  - Representational neglect, which is characterized by the failure to report left
      sided details of a mental image from memory, can occur after a right hemisphere
      lesion. In this study, we set out to verify the hypothesis that two distinct
      forms of representational neglect exist, one involving object representation and
      the other environmental representation. As representational neglect is considered
      rare, we also evaluated the prevalence and frequency of its association with
      perceptual neglect. We submitted a group of 96 unselected, consecutive, chronic,
      right brain-damaged patients to an extensive neuropsychological evaluation that
      included two representational neglect tests: the Familiar Square Description Test
      and the O'Clock Test. Representational neglect, as well as perceptual neglect,
      was present in about one-third of the sample. Most patients neglected the left
      side of imagined familiar squares but not the left side of imagined clocks. The
      present data show that representational neglect is not a rare disorder and also
      support the hypothesis that two different types of mental representations (i.e.
      topological and non-topological images) may be selectively damaged in
      representational neglect. 

PMID- 23874417
TI  - Awareness of and willingness to use oral pre-exposure prophylaxis for HIV
      prevention among HIV-serodiscordant heterosexual couples: a cross-sectional
      survey in Xinjiang, China.
AB  - OBJECTIVES: We aimed to investigate the awareness of and willingness to use oral
      pre-exposure prophylaxis (PrEP) for HIV prevention among HIV-negative partners in
      HIV-serodiscordant heterosexual couples in Xinjiang, China and determine factors
      that predict willingness to use oral PrEP. METHODS: Between November 2009 and
      December 2010, a cross-sectional survey was carried out among 351 HIV-negative
      partners in HIV-serodiscordant heterosexual couples from three cities in
      Xinjiang, China. Participants completed a self-administered questionnaire to
      assess their awareness of and willingness to use oral PrEP. Additionally, blood
      samples were collected to test for HIV infection. Univariate and multivariate
      logistic regression analyses were performed to identify predictors of willingness
      to use oral PrEP. RESULTS: Only 10 participants (2.8%) reported having heard of
      PrEP, and only two reported ever using PrEP. However, 297 (84.6%) reported that
      they were willing to use oral PrEP if it was proven to be both safe and
      effective. Results of multivariate analysis revealed the following independent
      predictors of willingness to use oral PrEP: monthly household income (adjusted
      odds ratio = 2.78, <1000 RMB vs. >= 1000 RMB, 95% confidence interval: 1.36
      5.69), perceived likelihood of contracting HIV from HIV-positive partner
      (adjusted odds ratio = 2.63, likely vs. unlikely, 95% confidence interval: 1.12
      6.19), and worrying about being discriminated against by others due to oral PrEP
      use (adjusted odds ratio = 9.43, No vs. Yes, 95% confidence interval: 3.78
      23.50). CONCLUSIONS: Our results showed HIV-negative partners in HIV
      serodiscordant heterosexual couples in China had low awareness of oral PrEP but
      high willingness to use oral PrEP for HIV prevention. Cost of oral PrEP should be
      taken into consideration in future PrEP prevention strategy. In addition, efforts
      should be made to reduce stigma attached to oral PrEP use, which may increase its
      acceptability among potential users.

PMID- 23874418
TI  - Loss of heterozygosity and copy number alterations in flow-sorted bulky cervical
      cancer.
AB  - Treatment choices for cervical cancer are primarily based on clinical FIGO stage
      and the post-operative evaluation of prognostic parameters including tumor
      diameter, parametrial and lymph node involvement, vaso-invasion, infiltration
      depth, and histological type. The aim of this study was to evaluate genomic
      changes in bulky cervical tumors and their relation to clinical parameters, using
      single nucleotide polymorphism (SNP)-analysis. Flow-sorted tumor cells and
      patient-matched normal cells were extracted from 81 bulky cervical tumors. DNA
      index (DI) measurement and whole genome SNP-analysis were performed. Data were
      analyzed to detect copy number alterations (CNA) and allelic balance state:
      balanced, imbalanced or pure LOH, and their relation to clinical parameters. The
      DI varied from 0.92-2.56. Pure LOH was found in >=40% of samples on chromosome
      arms 3p, 4p, 6p, 6q, and 11q, CN gains in >20% on 1q, 3q, 5p, 8q, and 20q, and
      losses on 2q, 3p, 4p, 11q, and 13q. Over 40% showed gain on 3q. The only
      significant differences were found between histological types (squamous, adeno
      and adenosquamous) in the lesser allele intensity ratio (LAIR) (p = 0.035) and in
      the CNA analysis (p = 0.011). More losses were found on chromosome-arm 2q (FDR =
      0.004) in squamous tumors and more gains on 7p, 7q, and 9p in adenosquamous
      tumors (FDR = 0.006, FDR = 0.004, and FDR = 0.029). Whole genome analysis of
      bulky cervical cancer shows widespread changes in allelic balance and CN. The
      overall genetic changes and CNA on specific chromosome-arms differed between
      histological types. No relation was found with the clinical parameters that
      currently dictate treatment choice. 

PMID- 23874419
TI  - Development and validation of a risk score predicting substantial weight gain
      over 5 years in middle-aged European men and women.
AB  - BACKGROUND: Identifying individuals at high risk of excess weight gain may help
      targeting prevention efforts at those at risk of various metabolic diseases
      associated with weight gain. Our aim was to develop a risk score to identify
      these individuals and validate it in an external population. METHODS: We used
      lifestyle and nutritional data from 53 degrees 758 individuals followed for a
      median of 5.4 years from six centers of the European Prospective Investigation
      into Cancer and Nutrition (EPIC) to develop a risk score to predict substantial
      weight gain (SWG) for the next 5 years (derivation sample). Assuming linear
      weight gain, SWG was defined as gaining >= 10% of baseline weight during follow
      up. Proportional hazards models were used to identify significant predictors of
      SWG separately by EPIC center. Regression coefficients of predictors were pooled
      using random-effects meta-analysis. Pooled coefficients were used to assign
      weights to each predictor. The risk score was calculated as a linear combination
      of the predictors. External validity of the score was evaluated in nine other
      centers of the EPIC study (validation sample). RESULTS: Our final model included
      age, sex, baseline weight, level of education, baseline smoking, sports activity,
      alcohol use, and intake of six food groups. The model's discriminatory ability
      measured by the area under a receiver operating characteristic curve was 0.64
      (95% CI = 0.63-0.65) in the derivation sample and 0.57 (95% CI = 0.56-0.58) in
      the validation sample, with variation between centers. Positive and negative
      predictive values for the optimal cut-off value of >= 200 points were 9% and 96%,
      respectively. CONCLUSION: The present risk score confidently excluded a large
      proportion of individuals from being at any appreciable risk to develop SWG
      within the next 5 years. Future studies, however, may attempt to further refine
      the positive prediction of the score.

PMID- 23874420
TI  - Phenotypic variation across chromosomal hybrid zones of the common shrew (Sorex
      araneus) indicates reduced gene flow.
AB  - Sorex araneus, the Common shrew, is a species with more than 70 karyotypic races,
      many of which form parapatric hybrid zones, making it a model for studying
      chromosomal speciation. Hybrids between races have reduced fitness, but
      microsatellite markers have demonstrated considerable gene flow between them,
      calling into question whether the chromosomal barriers actually do contribute to
      genetic divergence. We studied phenotypic clines across two hybrid zones with
      especially complex heterozygotes. Hybrids between the Novosibirsk and Tomsk races
      produce chains of nine and three chromosomes at meiosis, and hybrids between the
      Moscow and Seliger races produce chains of eleven. Our goal was to determine
      whether phenotypes show evidence of reduced gene flow at hybrid zones. We used
      maximum likelihood to fit tanh cline models to geometric shape data and found
      that phenotypic clines in skulls and mandibles across these zones had similar
      centers and widths as chromosomal clines. The amount of phenotypic
      differentiation across the zones is greater than expected if it were dissipating
      due to unrestricted gene flow given the amount of time since contact, but it is
      less than expected to have accumulated from drift during allopatric separation in
      glacial refugia. Only if heritability is very low, Ne very high, and the time
      spent in allopatry very short, will the differences we observe be large enough to
      match the expectation of drift. Our results therefore suggest that phenotypic
      differentiation has been lost through gene flow since post-glacial secondary
      contact, but not as quickly as would be expected if there was free gene flow
      across the hybrid zones. The chromosomal tension zones are confirmed to be
      partial barriers that prevent differentiated races from becoming phenotypically
      homogenous. 

PMID- 23874421
TI  - High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and
      metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic
      applications.
AB  - MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective
      miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the
      miRNA networks. To identify potential miRNA drugs in colorectal cancer, we
      profiled miRNA and mRNA expression in matching normal, tumor and metastasis
      tissues of eight patients by Illumina sequencing. We validated six miRNAs in a
      large tissue screen containing 16 additional tumor entities and identified miRNA
      1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the
      majority of cancers. Of these, we investigated miRNA-1 as representative in a
      systems-biology simulation of cellular cancer models implemented in PyBioS and
      assessed the effects of depletion as well as overexpression in terms of miRNA-1
      as a potential treatment option. In this system, miRNA-1 treatment reverted the
      disease phenotype with different effectiveness among the patients. Scoring the
      gene expression changes obtained through mRNA-Seq from the same patients we show
      that the combination of deep sequencing and systems biological modeling can help
      to identify patient-specific responses to miRNA treatments. We present this data
      as guideline for future pre-clinical assessments of new and personalized
      therapeutic options. 

PMID- 23874422
TI  - Radiation-induced temporal lobe injury for nasopharyngeal carcinoma: a comparison
      of intensity-modulated radiotherapy and conventional two-dimensional
      radiotherapy.
AB  - BACKGROUND: To compare the radiation-induced temporal lobe injury (TLI) in
      patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated
      radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).
      PATIENTS AND METHODS: 1276 cases of NPC treated with IMRT or 2D-CRT were
      retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic
      resonance imaging (MRI). RESULTS: The crude incidence of TLI was 7.5% and 10.8%
      (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for
      the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T
      stage (P<0.001) and radiation technique (P<0.001) as independent predictors.
      Patients with T1, T2 and T3 disease had a significantly higher risk when treated
      with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident
      for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the
      development of TLI (P<0.001). Those with T4 disease had a shorter median time to
      TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).
      CONCLUSIONS: IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of
      sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be
      addressed.

PMID- 23874423
TI  - Genotyping by genome reducing and sequencing for outbred animals.
AB  - Next-generation sequencing (NGS) approaches are widely used in genome-wide
      genetic marker discovery and genotyping. However, current NGS approaches are not
      easy to apply to general outbred populations (human and some major farm animals)
      for SNP identification because of the high level of heterogeneity and phase
      ambiguity in the haplotype. Here, we reported a new method for SNP genotyping,
      called genotyping by genome reducing and sequencing (GGRS) to genotype outbred
      species. Through an improved procedure for library preparation and a marker
      discovery and genotyping pipeline, the GGRS approach can genotype outbred species
      cost-effectively and high-reproducibly. We also evaluated the efficiency and
      accuracy of our approach for high-density SNP discovery and genotyping in a large
      genome pig species (2.8 Gb), for which more than 70,000 single nucleotide
      polymorphisms (SNPs) can be identified for an expenditure of only $80
      (USD)/sample. 

PMID- 23874424
TI  - Infrared warming reduced winter wheat yields and some physiological parameters,
      which were mitigated by irrigation and worsened by delayed sowing.
AB  - Winter wheat has a central role in ensuring the food security and welfare of 1.3
      billion people in China. Extensive previous studies have concluded that winter
      wheat yields would decrease with higher temperatures, owing to warming-induced
      soil drying or shortening of phenophase. Temperature in China is predicted to
      increase by 1-5 degrees C by 2100, which may greatly impact plant production and
      cause other negative effects. We performed a manipulative field experiment,
      creating diverse growth regimes for wheat by infrared radiation (IR) warming day
      and night, including IR warming only (DW), IR warming + delayed sowing dates
      (DS), IR warming + increased irrigation (IW), and a control (CK). The results
      show that IR warming increased daily average wheat canopy and soil temperatures
      by 2.0 degrees C and 2.3 degrees C, respectively. DW was associated with an
      advanced maturity of 10 days and yield reduction of 8.2%. IR-warming effects on
      the photosynthetic apparatus of wheat varied with season as well as significant
      differences were found in the booting stage. DS represented a worsened situation,
      lowering yield per plant by 16.4%, with a significant decline in aboveground
      biomass and functional leaf area. Wheat under DS showed double-peak patterns of
      diurnal gas exchange during booting stages and, consequently, lower
      photosynthetic capacity with high transpiration for cooling. Significantly lower
      actual water use efficiency and intrinsic water use efficiency from jointing to
      anthesis stages were also found under DS. However, IW had no significant
      difference from CK, irrespective of yield and photosynthesis. Therefore, we
      concluded that delayed sowing date may not be a good choice for winter wheat,
      whereas a thoroughly-watered wheat agroecosystem should be promoted in the
      context of global warming. 

PMID- 23874426
TI  - Building large collections of Chinese and English medical terms from semi
      structured and encyclopedia websites.
AB  - To build large collections of medical terms from semi-structured information
      sources (e.g. tables, lists, etc.) and encyclopedia sites on the web. The terms
      are classified into the three semantic categories, Medical Problems, Medications,
      and Medical Tests, which were used in i2b2 challenge tasks. We developed two
      systems, one for Chinese and another for English terms. The two systems share the
      same methodology and use the same software with minimum language dependent parts.
      We produced large collections of terms by exploiting billions of semi-structured
      information sources and encyclopedia sites on the Web. The standard performance
      metric of recall (R) is extended to three different types of Recall to take the
      surface variability of terms into consideration. They are Surface Recall (R(S)),
      Object Recall (R(O)), and Surface Head recall (R(H)). We use two test sets for
      Chinese. For English, we use a collection of terms in the 2010 i2b2 text. Two
      collections of terms, one for English and the other for Chinese, have been
      created. The terms in these collections are classified as either of Medical
      Problems, Medications, or Medical Tests in the i2b2 challenge tasks. The English
      collection contains 49,249 (Problems), 89,591 (Medications) and 25,107 (Tests)
      terms, while the Chinese one contains 66,780 (Problems), 101,025 (Medications),
      and 15,032 (Tests) terms. The proposed method of constructing a large collection
      of medical terms is both efficient and effective, and, most of all, independent
      of language. The collections will be made publicly available.

PMID- 23874425
TI  - Deep-sea bioluminescence blooms after dense water formation at the ocean surface.
AB  - The deep ocean is the largest and least known ecosystem on Earth. It hosts
      numerous pelagic organisms, most of which are able to emit light. Here we present
      a unique data set consisting of a 2.5-year long record of light emission by deep
      sea pelagic organisms, measured from December 2007 to June 2010 at the ANTARES
      underwater neutrino telescope in the deep NW Mediterranean Sea, jointly with
      synchronous hydrological records. This is the longest continuous time-series of
      deep-sea bioluminescence ever recorded. Our record reveals several weeks long,
      seasonal bioluminescence blooms with light intensity up to two orders of
      magnitude higher than background values, which correlate to changes in the
      properties of deep waters. Such changes are triggered by the winter cooling and
      evaporation experienced by the upper ocean layer in the Gulf of Lion that leads
      to the formation and subsequent sinking of dense water through a process known as
      "open-sea convection". It episodically renews the deep water of the study area
      and conveys fresh organic matter that fuels the deep ecosystems. Luminous
      bacteria most likely are the main contributors to the observed deep-sea
      bioluminescence blooms. Our observations demonstrate a consistent and rapid
      connection between deep open-sea convection and bathypelagic biological activity,
      as expressed by bioluminescence. In a setting where dense water formation events
      are likely to decline under global warming scenarios enhancing ocean
      stratification, in situ observatories become essential as environmental sentinels
      for the monitoring and understanding of deep-sea ecosystem shifts. 

PMID- 23874427
TI  - Differential effects of TipE and a TipE-homologous protein on modulation of
      gating properties of sodium channels from Drosophila melanogaster.
AB  - beta subunits of mammalian sodium channels play important roles in modulating the
      expression and gating of mammalian sodium channels. However, there are no
      orthologs of beta subunits in insects. Instead, an unrelated protein, TipE in
      Drosophila melanogaster and its orthologs in other insects, is thought to be a
      sodium channel auxiliary subunit. In addition, there are four TipE-homologous
      genes (TEH1-4) in D. melanogaster and three to four orthologs in other insect
      species. TipE and TEH1-3 have been shown to enhance the peak current of various
      insect sodium channels expressed in Xenopus oocytes. However, limited information
      is available on how these proteins modulate the gating of sodium channels,
      particularly sodium channel variants generated by alternative splicing and RNA
      editing. In this study, we compared the effects of TEH1 and TipE on the function
      of three Drosophila sodium channel splice variants, DmNav9-1, DmNav22, and
      DmNav26, in Xenopus oocytes. Both TipE and TEH1 enhanced the amplitude of sodium
      current and accelerated current decay of all three sodium channels tested.
      Strikingly, TEH1 caused hyperpolarizing shifts in the voltage-dependence of
      activation, fast inactivation and slow inactivation of all three variants. In
      contrast, TipE did not alter these gating properties except for a hyperpolarizing
      shift in the voltage-dependence of fast inactivation of DmNav26. Further analysis
      of the gating kinetics of DmNav9-1 revealed that TEH1 accelerated the entry of
      sodium channels into the fast inactivated state and slowed the recovery from both
      fast- and slow-inactivated states, thereby, enhancing both fast and slow
      inactivation. These results highlight the differential effects of TipE and TEH1
      on the gating of insect sodium channels and suggest that TEH1 may play a broader
      role than TipE in regulating sodium channel function and neuronal excitability in
      vivo. 

PMID- 23874429
TI  - Perceived self-efficacy and coping styles related to stressful critical life
      events.
AB  - OBJECTIVE: The study examined the personal resources, Self-efficacy and Coping
      Strategies, in a sample of pre-adolescents who experienced an emotionally and
      socially critical event, such as the earthquake of the 6(th) of April 2009,
      related to age and gender. METHODS: 198 pre-adolescents, 84 girls and 114 boys
      (Age Mean 12 years), attending Secondary School in L'Aquila meso-seismic area.
      The emotional, behavioural and social capacities have been assessed with specific
      questionnaires administered collectively ten months after the earthquake.
      RESULTS: Multidimensional analyses produced differentiated profiles according to
      gender and age: self-efficacy-perception and coping strategy profiles, based on
      quartiles calculations, revealed the difficulties of the subjects in estimating
      their ability to cope with the world of relations and emotions after the critical
      event. CONCLUSIONS: The intervention could be specific to the cognitive,
      emotional and relational state of children and adolescents and differentiated
      before (prevention), during (intervention) and after the event (intervention and
      prevention).

PMID- 23874428
TI  - Reconstruction of an integrated genome-scale co-expression network reveals key
      modules involved in lung adenocarcinoma.
AB  - Our goal of this study was to reconstruct a "genome-scale co-expression network"
      and find important modules in lung adenocarcinoma so that we could identify the
      genes involved in lung adenocarcinoma. We integrated gene mutation, GWAS, CGH,
      array-CGH and SNP array data in order to identify important genes and loci in
      genome-scale. Afterwards, on the basis of the identified genes a co-expression
      network was reconstructed from the co-expression data. The reconstructed network
      was named "genome-scale co-expression network". As the next step, 23 key modules
      were disclosed through clustering. In this study a number of genes have been
      identified for the first time to be implicated in lung adenocarcinoma by
      analyzing the modules. The genes EGFR, PIK3CA, TAF15, XIAP, VAPB, Appl1, Rab5a,
      ARF4, CLPTM1L, SP4, ZNF124, LPP, FOXP1, SOX18, MSX2, NFE2L2, SMARCC1, TRA2B,
      CBX3, PRPF6, ATP6V1C1, MYBBP1A, MACF1, GRM2, TBXA2R, PRKAR2A, PTK2, PGF and MYO10
      are among the genes that belong to modules 1 and 22. All these genes, being
      implicated in at least one of the phenomena, namely cell survival, proliferation
      and metastasis, have an over-expression pattern similar to that of EGFR. In few
      modules, the genes such as CCNA2 (Cyclin A2), CCNB2 (Cyclin B2), CDK1, CDK5,
      CDC27, CDCA5, CDCA8, ASPM, BUB1, KIF15, KIF2C, NEK2, NUSAP1, PRC1, SMC4, SYCE2,
      TFDP1, CDC42 and ARHGEF9 are present that play a crucial role in cell cycle
      progression. In addition to the mentioned genes, there are some other genes (i.e.
      DLGAP5, BIRC5, PSMD2, Src, TTK, SENP2, PSMD2, DOK2, FUS and etc.) in the modules.

PMID- 23874430
TI  - Variants in ZNRD1 gene predict HIV-1/AIDS disease progression in a Han Chinese
      population in Taiwan.
AB  - Patients demonstrate notable variations in disease progression following human
      immunodeficiency virus (HIV) infection. We aimed to identify ZNRD1 and RNF39
      genetic variants linked to AIDS progression. We conducted a genetic association
      study in HIV-1-infected Han Chinese patients residing in Taiwan. The clinical
      characteristics of 143 HIV-1-infected patients were measured, and patients were
      split into 2 groups: AIDS progression and AIDS non-progression. Genotyping of
      ZNRD1 and RNF39 was performed in all participants. We found that patients in the
      AIDS progression group had higher HIV-1 viral loads and lower CD4 cell counts
      than did patients in the AIDS non-progression group. The frequency of the AA
      genotype of ZNRD1 (rs16896970) was lower in the AIDS progression group than in
      the AIDS non-progression group. Patients with AA genotypes had lower levels of
      HIV-1 viral loads and higher levels of CD4 cell counts than did patients with
      AG+GG genotypes. AIDS progression in patients with the AA group is significantly
      different from that in patients with the AG and GG groups by using Kaplan-Meier
      survival analysis. The hazard ratio for progression was lower in the AA group
      than in the AG and GG groups. We identified a SNP that contributes to AIDS
      progression in HIV-1-infected patients in this population. This SNP had a
      significant protective influence on AIDS progression, and polymorphisms of the
      ZNRD1 gene may play a role in the pathogenesis of HIV-1 infection. 

PMID- 23874431
TI  - Human dermal stem/progenitor cell-derived conditioned medium ameliorates
      ultraviolet a-induced damage of normal human dermal fibroblasts.
AB  - Adult skin stem cells are considered an attractive cell resource for therapeutic
      potential in aged skin. We previously reported that multipotent human dermal
      stem/progenitor cells (hDSPCs) can be enriched from (normal human dermal
      fibroblasts (NHDFs) using collagen type IV. However, the beneficial effects of
      hDSPCs on aged skin remain to be elucidated. In the present study, we analyzed
      the growth factors secreted from hDSPCs in conditioned medium (CM) derived from
      hDSPCs (hDSPC-CM) and found that hDSPCs secreted higher levels of bFGF, IGFBP-1,
      IGFBP-2, HGF, VEGF and IGF-1 compared with non-hDSPCs. We then investigated
      whether hDSPC-CM has an effect on ultraviolet A (UVA)-irradiated NHDFs. Real-time
      RT-PCR analysis revealed that the treatment of UVA-irradiated NHDFs with hDSPC-CM
      significantly antagonized the UVA-induced up-regulation of the MMP1 and the UVA
      induced down-regulation of the collagen types I, IV and V and TIMP1 mRNA
      expressions. Furthermore, a scratch wound healing assay showed that hDSPC-CM
      enhanced the migratory properties of UVA-irradiated NHDFs. hDSPC-CM also
      significantly reduced the number of the early and late apoptotic cell population
      in UVA-irradiated NHDFs. Taken together, these data suggest that hDSPC-CM can
      exert some beneficial effects on aged skin and may be used as a therapeutic agent
      to improve skin regeneration and wound healing. 

PMID- 23874432
TI  - Characterization of microcirculation in multiple sclerosis lesions by dynamic
      texture parameter analysis (DTPA).
AB  - OBJECTIVE: Texture analysis is an alternative method to quantitatively assess MR
      images. In this study, we introduce dynamic texture parameter analysis (DTPA), a
      novel technique to investigate the temporal evolution of texture parameters using
      dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to
      introduce the method and its application on enhancing lesions (EL), non-enhancing
      lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis
      (MS). METHODS: We investigated 18 patients with MS and clinical isolated syndrome
      (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different
      field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within
      27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based
      texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of
      the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of
      the-variance statistical parameters were calculated. These TOI parameters were
      further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank
      testing corrected for multiple comparisons. RESULTS: Tissue- and time-dependent
      differences were observed in the dynamics of computed texture parameters. Sixteen
      parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant
      differences in the DTPA texture maps were found during inflow (52 parameters),
      outflow (40 parameters) and reperfusion (62 parameters). The strongest
      discriminators among the TPMs were observed in the variance-related parameters,
      while skewness and kurtosis TPMs were in general less sensitive to detect
      differences between the tissues. CONCLUSION: DTPA of DSCE image time series
      revealed characteristic time responses for ELs, NELs and NAWM. This may be
      further used for a refined quantitative grading of MS lesions during their
      evolution from acute to chronic state. DTPA discriminates lesions beyond features
      of enhancement or T2-hypersignal, on a numeric scale allowing for a more subtle
      grading of MS-lesions.

PMID- 23874433
TI  - Light scattering properties vary across different regions of the adult mouse
      brain.
AB  - Recently developed optogenetic tools provide powerful approaches to optically
      excite or inhibit neural activity. In a typical in-vivo experiment, light is
      delivered to deep nuclei via an implanted optical fiber. Light intensity
      attenuates with increasing distance from the fiber tip, determining the volume of
      tissue in which optogenetic proteins can successfully be activated. However,
      whether and how this volume of effective light intensity varies as a function of
      brain region or wavelength has not been systematically studied. The goal of this
      study was to measure and compare how light scatters in different areas of the
      mouse brain. We delivered different wavelengths of light via optical fibers to
      acute slices of mouse brainstem, midbrain and forebrain tissue. We measured light
      intensity as a function of distance from the fiber tip, and used the data to
      model the spread of light in specific regions of the mouse brain. We found
      substantial differences in effective attenuation coefficients among different
      brain areas, which lead to substantial differences in light intensity demands for
      optogenetic experiments. The use of light of different wavelengths additionally
      changes how light illuminates a given brain area. We created a brain atlas of
      effective attenuation coefficients of the adult mouse brain, and integrated our
      data into an application that can be used to estimate light scattering as well as
      required light intensity for optogenetic manipulation within a given volume of
      tissue. 

PMID- 23874435
TI  - Metabolomic profiles are gender, disease and time specific in the interleukin-10
      gene-deficient mouse model of inflammatory bowel disease.
AB  - Metabolomic profiling can be used to study disease-induced changes in
      inflammatory bowel diseases (IBD). The aim of this study was to investigate the
      difference in the metabolomic profile of males and females as they developed IBD.
      Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at
      age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic
      resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess
      differences in metabolomic profiles that occurred as a consequence of IBD
      development and severity (at week 20). These changes were contrasted to those
      that occurred as a consequence of gender. Our results demonstrate that both IL-10
      gene-deficient and wild-type mice exhibit gender-related changes in urinary
      metabolomic profile over time. Some male-female separating metabolites are common
      to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to
      be related predominantly to gender maturation. In addition, we were able to
      identify gender-separating metabolites that are unique for IL-10 gene-deficient
      and wild-type mice and, therefore, may be indicative of a gender-specific
      involvement in the development and severity of the intestinal inflammation. The
      comparison of the gender-separating metabolomic profile from IL-10 gene-deficient
      mice and wild-type mice during the development of IBD allowed us to identify
      changes in profile patterns that appear to be imperative in the development of
      intestinal inflammation, but yet central to gender-related differences in IBD
      development. The knowledge of metabolomic profile differences by gender and by
      disease severity has potential clinical implications in the design of both
      biomarkers of disease as well as the development of optimal therapies. 

PMID- 23874436
TI  - Eccrine sweat contains IL-1alpha, IL-1beta and IL-31 and activates epidermal
      keratinocytes as a danger signal.
AB  - Eccrine sweat is secreted onto the skin's surface and is not harmful to normal
      skin, but can exacerbate eczematous lesions in atopic dermatitis. Although
      eccrine sweat contains a number of minerals, proteins, and proteolytic enzymes,
      how it causes skin inflammation is not clear. We hypothesized that it stimulates
      keratinocytes directly, as a danger signal. Eccrine sweat was collected from the
      arms of healthy volunteers after exercise, and levels of proinflammatory
      cytokines in the sweat were quantified by ELISA. We detected the presence of IL
      1alpha, IL-1beta, and high levels of IL-31 in sweat samples. To investigate
      whether sweat activates keratinocytes, normal human keratinocytes were stimulated
      with concentrated sweat. Western blot analysis demonstrated the activation of NF
      kappaB, ERK, and JNK signaling in sweat-stimulated keratinocytes. Real-time PCR
      using total RNA and ELISA analysis of supernatants showed the upregulation of IL
      8 and IL-1beta by sweat. Furthermore, pretreatment with IL-1R antagonist blocked
      sweat-stimulated cytokine production and signal activation, indicating that
      bioactive IL-1 is a major factor in the activation of keratinocytes by sweat.
      Moreover, IL-31 seems to be another sweat stimulator that activates keratinocytes
      to produce inflammatory cytokine, CCL2. Sweat is secreted onto the skin's surface
      and does not come into contact with keratinocytes in normal skin. However, in
      skin with a defective cutaneous barrier, such as atopic dermatitis-affected skin,
      sweat cytokines can directly act on epidermal keratinocytes, resulting in their
      activation. In conclusion, eccrine sweat contains proinflammatory cytokines, IL-1
      and IL-31, and activates epidermal keratinocytes as a danger signal. 

PMID- 23874434
TI  - Dynamic regulation of hepatic lipid droplet properties by diet.
AB  - Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in
      neutral lipid storage, transport and metabolism through the actions of specific
      surface-associated proteins. Although diet and metabolism influence hepatic CLD
      levels, how they affect CLD protein composition is largely unknown. We used non
      biased, shotgun, proteomics in combination with metabolic analysis, quantitative
      immunoblotting, electron microscopy and confocal imaging to define the effects of
      low- and high-fat diets on CLD properties in fasted-refed mice. We found that the
      hepatic CLD proteome is distinct from that of CLD from other mammalian tissues,
      containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is
      also differentially affected by dietary fat content and hepatic metabolic status.
      High fat feeding markedly increased the CLD surface density of perilipin-2, a
      critical regulator of hepatic neutral lipid storage, whereas it reduced CLD
      levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of
      homocysteine levels linked to fatty liver disease and hepatocellular carcinoma.
      Collectively our data demonstrate that the hepatic CLD proteome is enriched in
      metabolic enzymes, and that it is qualitatively and quantitatively regulated by
      diet and metabolism. These findings implicate CLD in the regulation of hepatic
      metabolic processes, and suggest that their properties undergo reorganization in
      response to hepatic metabolic demands. 

PMID- 23874437
TI  - Dietary patterns, n-3 fatty acids intake from seafood and high levels of anxiety
      symptoms during pregnancy: findings from the Avon Longitudinal Study of Parents
      and Children.
AB  - BACKGROUND: Little is known about relationships between dietary patterns, n-3
      polyunsaturated fatty acids (PUFA) intake and excessive anxiety during pregnancy.
      OBJECTIVE: To examine whether dietary patterns and n-3 PUFA intake from seafood
      are associated with high levels of anxiety during pregnancy. DESIGN: Pregnant
      women enrolled from 1991-1992 in ALSPAC (n 9,530). Dietary patterns were
      established from a food frequency questionnaire using principal component
      analysis. Total intake of n-3 PUFA (grams/week) from seafood was also examined.
      Symptoms of anxiety were measured at 32 weeks of gestation with the Crown-Crisp
      Experiential Index; scores >= 9 corresponding to the 85(th) percentile was
      defined as high anxiety symptoms. Multivariate logistic regression models were
      used to estimate the OR and 95% CI, adjusted by socioeconomic and lifestyle
      variables. RESULTS: Multivariate results showed that women in the highest tertile
      of the health-conscious (OR 0.77; 0.65-0.93) and the traditional (OR 0.84; 0.73
      0.97) pattern scores were less likely to report high levels of anxiety symptoms.
      Women in the highest tertile of the vegetarian pattern score (OR 1.25; 1.08-1.44)
      were more likely to have high levels of anxiety, as well as those with no n-3
      PUFA intake from seafood (OR 1.53; 1.25-1.87) when compared with those with
      intake of >1.5 grams/week. CONCLUSIONS: The present study provides evidence of a
      relationship between dietary patterns, fish intake or n-3 PUFA intake from
      seafood and symptoms of anxiety in pregnancy, and suggests that dietary
      interventions could be used to reduce high anxiety symptoms during pregnancy.

PMID- 23874438
TI  - A lung segmental model of chronic Pseudomonas infection in sheep.
AB  - BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is a major
      contributor to morbidity, mortality and premature death in cystic fibrosis. A new
      paradigm for managing such infections is needed, as are relevant and translatable
      animal models to identify and test concepts. We sought to improve on limitations
      associated with existing models of infection in small animals through developing
      a lung segmental model of chronic Pseudomonas infection in sheep.
      METHODOLOGY/PRINCIPAL FINDINGS: Using local lung instillation of P. aeruginosa
      suspended in agar beads we were able to demonstrate that such infection led to
      the development of a suppurative, necrotising and pyogranulomatous pneumonia
      centred on the instilled beads. No overt evidence of organ or systemic compromise
      was apparent in any animal during the course of infection. Infection persisted in
      the lungs of individual animals for as long as 66 days after initial
      instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid
      derived from infected segments proved an insensitive index of the presence of
      significant infection in lung tissue (>10(4) cfu/g). CONCLUSIONS/SIGNIFICANCE:
      The agar bead model of chronic P. aeruginosa lung infection in sheep is a
      relevant platform to investigate both the pathobiology of such infections as well
      as novel approaches to their diagnosis and therapy. Particular ethical benefits
      relate to the model in terms of refining existing approaches by compromising a
      smaller proportion of the lung with infection and facilitating longitudinal
      assessment by bronchoscopy, and also potentially reducing animal numbers through
      facilitating within-animal comparisons of differential therapeutic approaches.

PMID- 23874439
TI  - Diabetes diminishes the portal-systemic collateral vascular response to
      vasopressin via vasopressin receptor and Galpha proteins regulations in cirrhotic
      rats.
AB  - Liver cirrhosis may lead to portal-systemic collateral formation and bleeding.
      The hemostatic effect is influenced by the response of collateral vessels to
      vasoconstrictors. Diabetes and glucose also influence vasoresponsiveness, but
      their net effect on collaterals remains unexplored. This study investigated the
      impact of diabetes or glucose application on portal-systemic collateral
      vasoresponsiveness to arginine vasopressin (AVP) in cirrhosis. Spraque-Dawley
      rats with bile duct ligation (BDL)-induced cirrhosis received vehicle (citrate
      buffer) or streptozotocin (diabetic, BDL/STZ). The in situ collateral perfusion
      was done after hemodynamic measurements: Both were perfused with Krebs solution,
      D-glucose, or D-glucose and NaF, with additional OPC-31260 for the BDL/STZ group.
      Splenorenal shunt vasopressin receptors and Galpha proteins mRNA expressions were
      evaluated. The survival rate of cirrhotic rats was decreased by STZ injection.
      The collateral perfusion pressure changes to AVP were lower in STZ-injected
      groups, which were reversed by OPC-31260 (a V2R antagonist) and overcome by NaF
      (a G protein activator). The splenorenal shunt V2R mRNA expression was increased
      while Galpha proteins mRNA expressions were decreased in BDL/STZ rats compared to
      BDL rats. The Galphaq and Galpha11 mRNA expressions also correlated with the
      maximal perfusion pressure changes to AVP. Diabetes diminished the portal
      systemic collateral vascular response to AVP in rats with BDL-induced cirrhosis,
      probably via V2 receptor up-regulation and Galpha proteins down-regulation. 

PMID- 23874440
TI  - Decoding the substrate supply to human neuronal nitric oxide synthase.
AB  - Nitric oxide, produced by the neuronal nitric oxide synthase (nNOS) from L
      arginine is an important second messenger molecule in the central nervous system:
      It influences the synthesis and release of neurotransmitters and plays an
      important role in long-term potentiation, long-term depression and neuroendocrine
      secretion. However, under certain pathological conditions such as Alzheimer's or
      Parkinson's disease, stroke and multiple sclerosis, excessive NO production can
      lead to tissue damage. It is thus desirable to control NO production in these
      situations. So far, little is known about the substrate supply to human nNOS as a
      determinant of its activity. Measuring bioactive NO via cGMP formation in
      reporter cells, we demonstrate here that nNOS in both, human A673
      neuroepithelioma and TGW-nu-I neuroblastoma cells can be fast and efficiently
      nourished by extracellular arginine that enters the cells via membrane
      transporters (pool I that is freely exchangeable with the extracellular space).
      When this pool was depleted, NO synthesis was partially sustained by
      intracellular arginine sources not freely exchangeable with the extracellular
      space (pool II). Protein breakdown made up by far the largest part of pool II in
      both cell types. In contrast, citrulline to arginine conversion maintained NO
      synthesis only in TGW-nu-I neuroblastoma, but not A673 neuroepithelioma cells.
      Histidine mimicked the effect of protease inhibitors causing an almost complete
      nNOS inhibition in cells incubated additionally in lysine that depletes the
      exchangeable arginine pool. Our results identify new ways to modulate nNOS
      activity by modifying its substrate supply. 

PMID- 23874441
TI  - Low rates of sustained virologic response with peginterferon plus ribavirin for
      chronic hepatitis C virus infection in HIV infected patients in Rio de Janeiro,
      Brazil.
AB  - BACKGROUND: The standard treatment for chronic hepatitis C virus (HCV) infection
      in HIV-infected subjects is the combination of alfapeginterferon (PEG-IFN) plus
      ribavirin. We designed this study to evaluate the rate of SVR and predictors of
      SVR in a public health setting in Rio de Janeiro, Brazil. METHODS: Retrospective
      cohort study of HCV/HIV co-infected patients treated with PEG-IFN plus ribavirin
      from 2004 to 2011 in 3 outpatient units in Rio de Janeiro. Exposure variables
      included age, sex, CD4+ cell count, HCV genotype, HCV and HIV viral loads, liver
      histology (METAVIR fibrosis scoring system) and previous treatment. The main
      outcome measurement was SVR. RESULTS: 100 patients were included in this
      analysis. Median age was 47 years and 68% were male. 80%, 4%, 14% and 2% were
      infected with HCV genotypes 1, 2, 3 and 4, respectively. At baseline, 77% had HCV
      viral load greater than 800,000 IU/ml, 99% had CD4+ greater than 200 cells/mm(3)
      and 10% had a diagnosis of cirrhosis. The treatment was withdrawn in 9% of the
      subjects (5% with adverse effects and 4% dropped out). SVR was observed in 27
      (27%) of the 100 patients included. 13 (13%) subjects were classified as null
      responders, 33(33%) as non-responders, 9 (9%) as breakthrough and 9(9%) as
      relapsers. In the multivariate model only being infected with genotype 2 or 3
      (p<0.01) and having low levels of gamma glutamyl transferase (GGT) at baseline (p
      = 0.04), were predictive of SVR. CONCLUSION: SVR in HCV/HIV co-infected subjects
      in a public health setting is similar to that observed in clinical trials, albeit
      very low. A delay in therapy initiation should be considered until new therapies
      as direct acting antiviral drugs (DAA) become widely available and tested in
      coinfected subjects.

PMID- 23874442
TI  - Molecular characterization of Streptococcus agalactiae isolated from bovine
      mastitis in Eastern China.
AB  - One hundred and two Streptococcus agalactiae (group B streptococcus [GBS])
      isolates were collected from dairy cattle with subclinical mastitis in Eastern
      China during 2011. Clonal groups were established by multilocus sequence typing
      (MLST) and pulsed-field gel electrophoresis (PFGE), respectively. Capsular
      polysaccharides (CPS), pilus and alpha-like-protein (Alp) family genes were also
      characterized by molecular techniques. MLST analysis revealed that these isolates
      were limited to three clonal groups and were clustered in six different lineages,
      i.e. ST (sequence type) 103, ST568, ST67, ST301, ST313 and ST570, of which ST568
      and ST570 were new genotypes. PFGE analysis revealed this isolates were clustered
      in 27 PFGE types, of which, types 7, 8, 14, 15, 16, 18, 23 and 25 were the eight
      major types, comprising close to 70% (71/102) of all the isolates. The most
      prevalent sequence types were ST103 (58% isolates) and ST568 (31% isolates),
      comprising capsular genotype Ia isolates without any of the detected Alp genes,
      suggesting the appearance of novel genomic backgrounds of prevalent strains of
      bovine S. agalactiae. All the strains possessed the pilus island 2b (PI-2b) gene
      and the prevalent capsular genotypes were types Ia (89% isolates) and II (11%
      isolates), the conserved pilus type providing suitable data for the development
      of vaccines against mastitis caused by S. agalactiae. 

PMID- 23874443
TI  - Household transmission of rotavirus in a community with rotavirus vaccination in
      Quininde, Ecuador.
AB  - BACKGROUND: We studied the transmission of rotavirus infection in households in
      peri-urban Ecuador in the vaccination era. METHODS: Stool samples were collected
      from household contacts of child rotavirus cases, diarrhea controls and healthy
      controls following presentation of the index child to health facilities.
      Rotavirus infection status of contacts was determined by RT-qPCR. We examined
      factors associated with transmissibility (index-case characteristics) and
      susceptibility (household-contact characteristics). RESULTS: Amongst cases,
      diarrhea controls and healthy control household contacts, infection attack rates
      (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher
      from index cases with vomiting, and amongst siblings. Disease ARs were higher
      when the index child was <18 months and had vomiting, with household contact <10
      years and those sharing a room with the index case being more susceptible. We
      found no evidence of asymptomatic infections leading to disease transmission.
      CONCLUSION: Transmission rates of rotavirus are high in households with an
      infected child, while background infections are rare. We have identified factors
      associated with transmission (vomiting/young age of index case) and
      susceptibility (young age/sharing a room/being a sibling of the index case).
      Vaccination may lead to indirect benefits by averting episodes or reducing
      symptoms in vaccinees.

PMID- 23874444
TI  - Increased baseline proinflammatory cytokine production in chronic hepatitis C
      patients with rapid virological response to peginterferon plus ribavirin.
AB  - BACKGROUND: Chronic hepatitis C (CHC) patients achieving rapid virological
      response (RVR) on PEG-IFN/ribavirin (P/R) therapy have high chance of sustained
      virological response (SVR). To analyze host immunological factors associated with
      RVR, viral kinetics, phenotype distribution and Th1/Th2 cytokine production by
      peripheral blood mononuclear cells (PBMC) were studied prior to and during P/R
      therapy. METHODS: TNF-alpha, IFN-gamma, IL-2, IL-6, IL-4 and IL-10 production by
      PBMC were measured after Toll-like receptor 4 (TLR-4) or phorbol myristate
      acetate/Ionomycin stimulation in 20 healthy controls and in 50 CHC patients
      before receiving and during P/R therapy. RVR was achieved by 14, complete early
      virological response (cEVR) by 19 patients and 17 patients were null-responders
      (NR). RESULTS: Patients with RVR showed an increased baseline TNF-alpha and IL-6
      production by TLR-4 activated monocytes and increased IFN-gamma, decreased IL-4
      and IL-10 production by lymphocytes compared to non-RVR patients. SVR was also
      associated with increased baseline TNF-alpha production and decreased IL-10
      levels compared to patients who did not achieve SVR. Baseline IL-2 production was
      higher in cEVR compared to NR patients. Antiviral treatment increased TNF-alpha,
      IL-6 production by monocytes and IFN-gamma secretion by lymphocytes and decreased
      IL-4 and IL-10 production by lymphocytes in cEVR compared to NR patients.
      CONCLUSION: RVR was associated with increased baseline proinflammatory cytokine
      production by TLR-4 stimulated monocytes and by activated lymphocytes. In null
      responders and in patients who did not achieve SVR both TLR-4 sensing function
      and proinflammatory cytokine production were impaired, suggesting that modulation
      of TLR activity and controlled induction of inflammatory cytokine production may
      provide further therapeutic strategy for CHC patients non-responding to P/R
      treatment.

PMID- 23874445
TI  - Psychosis-proneness and neural correlates of self-inhibition in theory of mind.
AB  - Impaired Theory of Mind (ToM) has been repeatedly reported as a feature of
      psychotic disorders. ToM is crucial in social interactions and for the
      development of social behavior. It has been suggested that reasoning about the
      belief of others, requires inhibition of the self-perspective. We investigated
      the neural correlates of self-inhibition in nineteen low psychosis prone (PP) and
      eighteen high PP subjects presenting with subclinical features. High PP subjects
      have a more than tenfold increased risk of developing a schizophrenia-spectrum
      disorder. Brain activation was measured with functional Magnetic Resonance
      Imaging during a ToM task differentiating between self-perspective inhibition and
      belief reasoning. Furthermore, to test underlying inhibitory mechanisms, we
      included a stop-signal task. We predicted worse behavioral performance for high
      compared to low PP subjects on both tasks. Moreover, based on previous
      neuroimaging results, different activation patterns were expected in the inferior
      frontal gyrus (IFG) in high versus low PP subjects in self-perspective inhibition
      and simple response inhibition. Results showed increased activation in left IFG
      during self-perspective inhibition, but not during simple response inhibition,
      for high PP subjects as compared to low PP subjects. High and low PP subjects
      showed equal behavioral performance. The results suggest that at a neural level,
      high PP subjects need more resources for inhibiting the self-perspective, but not
      for simple motor response inhibition, to equal the performance of low PP
      subjects. This may reflect a compensatory mechanism, which may no longer be
      available for patients with schizophrenia-spectrum disorders resulting in ToM
      impairments. 

PMID- 23874446
TI  - Potential effects of climate change on the water level, flora and macro-fauna of
      a large neotropical wetland.
AB  - Possible consequences of climate change in one of the world's largest wetlands
      (Ibera, Argentina) were analysed using a multi-scale approach. Climate
      projections coupled to hydrological models were used to analyse variability in
      wetland water level throughout the current century. Two potential scenarios of
      greenhouse gas emissions were explored, both resulting in an increase in the
      inter-annual fluctuations of the water level. In the scenario with higher
      emissions, projections also showed a long-term negative trend in water-level. To
      explore the possible response of biota to such water-level changes, species-area
      relationships of flora and aerial censuses of macro-fauna were analysed during an
      extraordinary dry period. Plant species richness at the basin scale was found to
      be highly resistant to hydrological changes, as the large dimension of the
      wetland acts to buffer against the water-level variations. However, local
      diversity decreased significantly with low water levels, leading to the loss of
      ecosystem resilience to additional stressors. The analysis of macro-fauna
      populations suggested that wetland provides refuge, in low water periods, for the
      animals with high dispersal ability (aquatic and migratory birds). On the
      contrary, the abundance of animals with low dispersal ability (mainly herbivorous
      species) was negatively impacted in low water periods, probably because they are
      required to search for alternative resources beyond the wetland borders. This
      period of resource scarcity was also related to increased mortality of large
      mammals (e.g. marsh deer) around water bodies with high anthropogenic enrichment
      and cyanobacteria dominance. The synergy between recurrent climatic fluctuations
      and additional stressors (i.e. biological invasions, eutrophication) presents an
      important challenge to the conservation of neotropical wetlands in the coming
      decades. 

PMID- 23874447
TI  - Gene expression analysis of zebrafish melanocytes, iridophores, and retinal
      pigmented epithelium reveals indicators of biological function and developmental
      origin.
AB  - In order to facilitate understanding of pigment cell biology, we developed a
      method to concomitantly purify melanocytes, iridophores, and retinal pigmented
      epithelium from zebrafish, and analyzed their transcriptomes. Comparing
      expression data from these cell types and whole embryos allowed us to reveal gene
      expression co-enrichment in melanocytes and retinal pigmented epithelium, as well
      as in melanocytes and iridophores. We found 214 genes co-enriched in melanocytes
      and retinal pigmented epithelium, indicating the shared functions of melanin
      producing cells. We found 62 genes significantly co-enriched in melanocytes and
      iridophores, illustrative of their shared developmental origins from the neural
      crest. This is also the first analysis of the iridophore transcriptome. Gene
      expression analysis for iridophores revealed extensive enrichment of specific
      enzymes to coordinate production of their guanine-based reflective pigment. We
      speculate the coordinated upregulation of specific enzymes from several metabolic
      pathways recycles the rate-limiting substrate for purine synthesis,
      phosphoribosyl pyrophosphate, thus constituting a guanine cycle. The purification
      procedure and expression analysis described here, along with the accompanying
      transcriptome-wide expression data, provide the first mRNA sequencing data for
      multiple purified zebrafish pigment cell types, and will be a useful resource for
      further studies of pigment cell biology. 

PMID- 23874448
TI  - Insulin receptor-overexpressing beta-cells ameliorate hyperglycemia in diabetic
      rats through Wnt signaling activation.
AB  - To investigate the therapeutic efficacy and mechanism of beta-cells with insulin
      receptor (IR) overexpression on diabetes mellitus (DM), rat insulinoma (INS-1)
      cells were engineered to stably express human insulin receptor (INS-IR cells),
      and subsequently transplanted into streptozotocin- induced diabetic rats.
      Compared with INS-1 cells, INS-IR cells showed improved beta-cell function,
      including the increase in glucose utilization, calcium mobilization, and insulin
      secretion, and exhibited a higher rate of cell proliferation, and maintained
      lower levels of blood glucose in diabetic rats. These results were attributed to
      the increase of beta-catenin/PPARgamma complex bindings to peroxisome
      proliferator response elements in rat glucokinase (GK) promoter and the
      prolongation of S-phase of cell cycle by cyclin D1. These events resulted from
      more rapid and higher phosphorylation levels of insulin-signaling intermediates,
      including insulin receptor substrate (IRS)-1/IRS-2/phosphotylinositol 3 kinase/v
      akt murine thymoma viral oncogene homolog (AKT) 1, and the consequent enhancement
      of beta-catenin nuclear translocation and Wnt responsive genes including GK and
      cyclin D1. Indeed, the higher functionality and proliferation shown in INS-IR
      cells were offset by beta-catenin, cyclin D1, GK, AKT1, and IRS-2 gene depletion.
      In addition, the promotion of cell proliferation and insulin secretion by Wnt
      signaling activation was shown by 100 nM insulin treatment, and to a similar
      degree, was shown in INS-IR cells. In this regard, this study suggests that
      transferring INS-IR cells into diabetic animals is an effective and feasible DM
      treatment. Accordingly, the method might be a promising alternative strategy for
      treatment of DM given the adverse effects of insulin among patients, including
      the increased risk of modest weight gain and hypoglycemia. Additionally, this
      study demonstrates that the novel mechanism of cross-talk between insulin and Wnt
      signaling plays a primary role in the higher therapeutic efficacy of IR
      overexpressing beta-cells. 

PMID- 23874449
TI  - Structural modulation of brain development by oxygen: evidence on adolescents
      migrating from high altitude to sea level environment.
AB  - The present study aimed to investigate structural modulation of brain by high
      level of oxygen during its peak period of development. Voxel-based morphometry
      analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based
      Spatial Statistics analysis of WM fractional anisotropy (FA) and mean diffusion
      (MD) based on MRI images were carried out on 21 Tibetan adolencents (15-18
      years), who were born and raised in Qinghai-Tibetan Plateau (2900-4700 m) and
      have lived at sea level (SL) in the last 4 years. The control group consisted of
      matched Tibetan adolescents born and raised at high altitude all the time. SL
      immigrants had increased GM volume in the left insula, left inferior parietal
      gyrus, and right superior parietal gyrus and decreased GM in the left precentral
      cortex and multiple sites in cerebellar cortex (left lobule 8, bilateral lobule 6
      and crus 1/2). Decreased WM volume was found in the right superior frontal gyrus
      in SL immigrants. SL immigrants had higher FA and lower MD at multiple sites of
      WM tracts. Moreover, we detected changes in ventilation and circulation. GM
      volume in cerebellum lobule 8 positively correlated with diastolic pressure,
      while GM volume in insula positively correlated vital capacity and hypoxic
      ventilatory response. Our finding indicate that the structural modulations of GM
      by high level of oxygen during its peak period of development are related to
      respiratory and circulatory regulations, while the modulation in WM mainly
      exhibits an enhancement in myelin maturation. 

PMID- 23874450
TI  - Association of hepatic lipase -514T allele with coronary artery disease and ankle
      brachial index, dependence on the lipoprotein phenotype: the GENES study.
AB  - OBJECTIVES: Relationship between hepatic lipase (LIPC) polymorphism and coronary
      artery disease (CAD) has often led to contradictory results. We studied this
      relation by genotyping rs1800588 in the LIPC promoter in a case-control study on
      CAD (the GENES study). We also investigated the relationship between this
      polymorphism and the ankle-brachial index (ABI), which is predictive of
      atherosclerosis progression and complications in patients at high cardiovascular
      risk. METHODS: 557 men aged 45-74 with stable coronary artery disease and 560
      paired controls were genotyped for rs1800588. Medical data, clinical examination
      including determination of ABI and biological measurements related to
      cardiovascular risk factors enabled multivariate analyses and multiple
      adjustments. RESULTS: CAD cases showed a higher T-allele frequency than controls
      (0.246 vs 0.192, p = 0.003). An interaction has been found between LIPC
      polymorphism and triglycerides (TG) levels regarding risk of CAD: TT-homozigosity
      was associated with an Odds ratio (OR) of 6.4 (CI: 1.8-22.3) when TG were below
      1.5 g/L, but no association was found at higher TG levels (OR = 1.34, CI: 0.3
      5.9). The distribution of LIPC genotypes was compared between CAD patients with
      normal or abnormal ABI and impact of LIPC polymorphism on ABI was determined.
      Following multiple adjustments, association of the T-allele with pejorative ABI
      (<0.90) was significant for heterozygotes and for all T-carriers (OR = 1.55, CI:
      1.07-2.25). CONCLUSION: The -514T LIPC allele is associated with CAD under
      normotriglyceridemic conditions and constitutes an independent determinant of
      pejorative ABI in coronary patients.

PMID- 23874451
TI  - The asymmetric binding of PGC-1alpha to the ERRalpha and ERRgamma nuclear
      receptor homodimers involves a similar recognition mechanism.
AB  - BACKGROUND: PGC-1alpha is a crucial regulator of cellular metabolism and energy
      homeostasis that functionally acts together with the estrogen-related receptors
      (ERRalpha and ERRgamma) in the regulation of mitochondrial and metabolic gene
      networks. Dimerization of the ERRs is a pre-requisite for interactions with PGC
      1alpha and other coactivators, eventually leading to transactivation. It was
      suggested recently (Devarakonda et al) that PGC-1alpha binds in a strikingly
      different manner to ERRgamma ligand-binding domains (LBDs) compared to its mode
      of binding to ERRalpha and other nuclear receptors (NRs), where it interacts
      directly with the two ERRgamma homodimer subunits. METHODS/PRINCIPAL FINDINGS:
      Here, we show that PGC-1alpha receptor interacting domain (RID) binds in an
      almost identical manner to ERRalpha and ERRgamma homodimers. Microscale
      thermophoresis demonstrated that the interactions between PGC-1alpha RID and ERR
      LBDs involve a single receptor subunit through high-affinity, ERR-specific L3 and
      low-affinity L2 interactions. NMR studies further defined the limits of PGC
      1alpha RID that interacts with ERRs. Consistent with these findings, the solution
      structures of PGC-1alpha/ERRalpha LBDs and PGC-1alpha/ERRgamma LBDs complexes
      share an identical architecture with an asymmetric binding of PGC-1alpha to
      homodimeric ERR. CONCLUSIONS/SIGNIFICANCE: These studies provide the molecular
      determinants for the specificity of interactions between PGC-1alpha and the ERRs,
      whereby negative cooperativity prevails in the binding of the coactivators to
      these receptors. Our work indicates that allosteric regulation may be a general
      mechanism controlling the binding of the coactivators to homodimers.

PMID- 23874452
TI  - A functional promoter polymorphism of IFITM3 is associated with susceptibility to
      pediatric tuberculosis in Han Chinese population.
AB  - A susceptibility locus for tuberculosis, a re-emerging infectious disease
      throughout the world, was previously discovered to exist on chromosome 11p15.
      IFITM3 gene encoding for interferon inducible transmembrane protein 3, is located
      at 11p15. It acts as an effector molecule for interferon-gamma, which is
      essential for anti-tuberculosis immune response. In order to investigate the
      association between susceptibility to TB and genetic polymorphisms of the IFITM3
      core promoter, a case-control study including 368 TB patients and 794 healthy
      controls was performed in Han Chinese children in northern China. The rs3888188
      polymorphism showed significant association with susceptibility to TB. The
      rs3888188 G allele, acting recessively, was more frequent in TB patients (95%
      confidence interval: 1.08-1.56, Bonferroni P-value: 0.039). We further assessed
      the effect of rs3888188 polymorphism on IFITM3 transcription in vitro. As based
      on luciferase promoter assays, the promoter activity of haplotypes with rs3888188
      G allele was lower than that of haplotypes with rs3888188 T allele. Moreover,
      peripheral-blood mononuclear cells carrying rs3888188 GG genotype showed a
      reduced IFITM3 mRNA level compared to cells carrying TT or GT genotype. In
      conclusion, rs3888188, a functional promoter polymorphism of IFITM3, was
      identified to influence the risk for pediatric TB in Han Chinese population. 

PMID- 23874453
TI  - An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts
      mycobacterial infection.
AB  - While tuberculosis susceptibility has historically been ascribed to failed
      inflammation, it is now known that an excess of leukotriene A4 hydrolase (LTA4H),
      which catalyzes the final step in leukotriene B4 (LTB4) synthesis, produces a
      hyperinflammatory state and tuberculosis susceptibility. Here we show that the
      LTB4-inactivating enzyme leukotriene B4 dehydrogenase/prostaglandin reductase 1
      (LTB4DH/PTGR1) restricts inflammation and independently confers resistance to
      tuberculous infection. LTB4DH overexpression counters the susceptibility
      resulting from LTA4H excess while ltb4dh-deficient animals can be rescued
      pharmacologically by LTB4 receptor antagonists. These data place LTB4DH as a key
      modulator of TB susceptibility and suggest new tuberculosis therapeutic
      strategies. 

PMID- 23874454
TI  - Background strain and the differential susceptibility of podocyte-specific
      deletion of Myh9 on murine models of experimental glomerulosclerosis and HIV
      nephropathy.
AB  - We previously reported that podocyte-specific deletion of Myh9 (conventional
      myosin heavy chain 2A) in C57BL/6 mice does not cause spontaneous kidney disease
      but instead results in a predisposition to glomerulosclerosis in response to a
      second model of glomerular injury. In contrast, other investigators reported that
      podocyte-specific deletion of Myh9 (PodDeltaMyh9) resulted in spontaneous
      glomerulosclerosis in mice on a mixed background, suggesting that the
      glomerulosclerosis is dependent on background strain. In order to elucidate the
      cause of this strain dependent effect Podocin::Cre and Myh9(flox) alleles were
      backcrossed to mouse strain FVB/N, which is highly susceptible to
      glomerulosclerosis, with the aim of intercrossing susceptible FVB/N and resistant
      C57BL/6 mice in subsequent congenic analyses. However, after backcrossing mice to
      FVB/N and aging mice to 28 weeks, we found no evidence of glomerular disease in
      PodDeltaMyh9 mice vs control littermates (urine MAC ratio all p>0.05). We also
      tested C57BL/6 PodDeltaMyh9 mice for a predisposition to injury from models other
      than Adriamycin including HIV nephropathy (HIVAN), puromycin nephropathy, and
      sheep nephrotoxic serum. In the Tg26 model of HIVAN, we found that podocyte
      specific deletion of Myh9 resulted in a modest hypersensitivity in adults
      compared to Tg26+ control littermates (urine MAC ratio, p<0.05 or less). In
      contrast, we found that PodDeltaMyh9 mice were not predisposed to injury in
      response to other injury models including puromycin nephropathy and sheep
      nephrotoxic serum. While the mechanism of injury in these models is not fully
      understood, we conclude that PodDeltaMyh9 results in a variable susceptibility to
      glomerulosclerosis in response to different models of glomerular injury. In
      addition, based on the lack of a spontaneous phenotype of glomerulosclerosis in
      both C57BL/6 and FVB/N mice, we propose that Myh9 is not absolutely required in
      adult podocytes. 

PMID- 23874456
TI  - The role of balanced training and testing data sets for binary classifiers in
      bioinformatics.
AB  - Training and testing of conventional machine learning models on binary
      classification problems depend on the proportions of the two outcomes in the
      relevant data sets. This may be especially important in practical terms when real
      world applications of the classifier are either highly imbalanced or occur in
      unknown proportions. Intuitively, it may seem sensible to train machine learning
      models on data similar to the target data in terms of proportions of the two
      binary outcomes. However, we show that this is not the case using the example of
      prediction of deleterious and neutral phenotypes of human missense mutations in
      human genome data, for which the proportion of the binary outcome is unknown. Our
      results indicate that using balanced training data (50% neutral and 50%
      deleterious) results in the highest balanced accuracy (the average of True
      Positive Rate and True Negative Rate), Matthews correlation coefficient, and area
      under ROC curves, no matter what the proportions of the two phenotypes are in the
      testing data. Besides balancing the data by undersampling the majority class,
      other techniques in machine learning include oversampling the minority class,
      interpolating minority-class data points and various penalties for misclassifying
      the minority class. However, these techniques are not commonly used in either the
      missense phenotype prediction problem or in the prediction of disordered residues
      in proteins, where the imbalance problem is substantial. The appropriate approach
      depends on the amount of available data and the specific problem at hand. 

PMID- 23874455
TI  - Functional regulatory role of STAT3 in HPV16-mediated cervical carcinogenesis.
AB  - Signal transducer and activator of transcription 3 (STAT3) is an oncogenic
      transcription factor constitutively active and aberrantly expressed in cervical
      cancer. However, the functional role of STAT3 in regulation of HPV's viral
      oncogene expression and downstream events associated with cervical carcinogenesis
      is not known. Our present study performed on HPV16-positive cervical cancer cell
      lines (SiHa and CaSki) and primary tumor tissues revealed a strong positive
      correlation of constitutively active STAT3 with expression of HPV16 E6 and E7
      oncoproteins and a negative association with levels of p53 and pRB. Pharmacologic
      targeting of STAT3 expression in cervical cancer cell lines either by STAT3
      specific siRNA or blocking its tyrosine phosphorylation by AG490 or curcumin led
      to dose-dependent accumulation of p53 and pRb in cervical cancer cells.
      Interestingly, the suppression of STAT3 expression or activation was associated
      with the gradual loss of HPV16 E6 and E7 expression and was accompanied by loss
      of cell viability. The viability loss was specifically high in HPV16-positive
      cells as compared to HPV negative C33a cells. These findings substantiate the
      regulatory role of STAT3 in HPV16-mediated cervical carcinogenesis. Leads
      obtained from the present study provide a strong rationale for developing novel
      STAT3-based approaches for therapeutic interventions against HPV infection to
      control cervical cancer. 

PMID- 23874458
TI  - Winning the genetic lottery: biasing birth sex ratio results in more
      grandchildren.
AB  - Population dynamics predicts that on average parents should invest equally in
      male and female offspring; similarly, the physiology of mammalian sex
      determination is supposedly stochastic, producing equal numbers of sons and
      daughters. However, a high quality parent can maximize fitness by biasing their
      birth sex ratio (SR) to the sex with the greatest potential to disproportionately
      outperform peers. All SR manipulation theories share a fundamental prediction:
      grandparents who bias birth SR should produce more grandoffspring via the favored
      sex. The celebrated examples of biased birth SRs in nature consistent with SR
      manipulation theories provide compelling circumstantial evidence. However, this
      prediction has never been directly tested in mammals, primarily because the
      complete three-generation pedigrees needed to test whether individual favored
      offspring produce more grandoffspring for the biasing grandparent are essentially
      impossible to obtain in nature. Three-generation pedigrees were constructed using
      90 years of captive breeding records from 198 mammalian species. Male and female
      grandparents consistently biased their birth SR toward the sex that maximized
      second-generation success. The most strongly male-biased granddams and grandsires
      produced respectively 29% and 25% more grandoffspring than non-skewing
      conspecifics. The sons of the most male-biasing granddams were 2.7 times as
      fecund as those of granddams with a 50?50 bias (similar results are seen in
      grandsires). Daughters of the strongest female-biasing granddams were 1.2 times
      as fecund as those of non-biasing females (this effect is not seen in
      grandsires). To our knowledge, these results are the first formal test of the
      hypothesis that birth SR manipulation is adaptive in mammals in terms of
      grandchildren produced, showing that SR manipulation can explain biased birth SR
      in general across mammalian species. These findings also have practical
      implications: parental control of birth SR has the potential to accelerate
      genetic loss and risk of extinction within captive populations of endangered
      species. 

PMID- 23874457
TI  - Targeted lipidomics in Drosophila melanogaster identifies novel 2
      monoacylglycerols and N-acyl amides.
AB  - Lipid metabolism is critical to coordinate organ development and physiology in
      response to tissue-autonomous signals and environmental cues. Changes to the
      availability and signaling of lipid mediators can limit competitiveness,
      adaptation to environmental stressors, and augment pathological processes. Two
      classes of lipids, the N-acyl amides and the 2-acyl glycerols, have emerged as
      important signaling molecules in a wide range of species with important signaling
      properties, though most of what is known about their cellular functions is from
      mammalian models. Therefore, expanding available knowledge on the repertoire of
      these lipids in invertebrates will provide additional avenues of research aimed
      at elucidating biosynthetic, metabolic, and signaling properties of these
      molecules. Drosophila melanogaster is a commonly used organism to study
      intercellular communication, including the functions of bioactive lipids.
      However, limited information is available on the molecular identity of lipids
      with putative biological activities in Drosophila. Here, we used a targeted
      lipidomics approach to identify putative signaling lipids in third instar
      Drosophila larvae, possessing particularly large lipid mass in their fat body. We
      identified 2-linoleoyl glycerol, 2-oleoyl glycerol, and 45 N-acyl amides in
      larval tissues, and validated our findings by the comparative analysis of Oregon
      RS, Canton-S and w1118 strains. Data here suggest that Drosophila represent
      another model system to use for the study of 2-acyl glycerol and N-acyl amide
      signaling. 

PMID- 23874459
TI  - A xenogeneic-free protocol for isolation and expansion of human adipose stem
      cells for clinical uses.
AB  - Human adipose stem cells (HASCS) play a crucial role in the fields of
      regenerative medicine and tissue engineering for different reasons: the abundance
      of adipose tissue, their easy harvesting, the ability to multipotent
      differentiation and the fact that they do not trigger allogeneic blood response
      or secrete cytokines that act as immunosuppressants. The vast majority of
      protocols use animal origin reagents, with the underlying risk of transmitting
      infections by non-human pathogens. We have designed a protocol to isolate and
      maintain the properties of hASCs avoiding xenogeneic reagents. These changes not
      only preserve hASCs morphology, but also increase cell proliferation and maintain
      their stem cell marker profile. On the other hand, human serum albumin (HSA),
      Tryple(r) and human Serum (HS), do not affect hASCs multipotent differentiation
      ability. The amendments introduced do not trigger modifications in the
      transcriptional profile of hASCs, alterations in key biochemical pathways or
      malignization. Thus, we have proven that it is possible to isolate and maintain
      hASCs avoiding animal reagents and, at the same time, preserving crucial culture
      parameters during long term culture. Thereby we have revealed a novel and
      effective tool for the improvement of clinical, cell-based therapies.

PMID- 23874460
TI  - Are anomalous invasion speeds robust to demographic stochasticity?
AB  - Two important issues for conservation are the range expansion of species as a
      result of climate change and the invasion of exotic species. Being able to
      predict the rate at which species spread is key for successful management. In
      deterministic models, the invasion speed of a polymorphic population can be
      faster than that of any of the component phenotypes, and these "anomalous"
      invasion speeds persist even when the mutation rate between phenotypes is
      vanishingly small. Here we investigate whether the same phenomenon is observed in
      a model with demographic stochasticity. The model that we use is discrete in time
      and space and we carry out numerical simulations to determine the invasion speed
      of a population that has two morphs which differ in their dispersal abilities. We
      find that anomalous speeds are observed in the stochastic model, but only when
      the carrying capacity of the population is large or the mutation rate between
      morphs is high enough. These results suggest that only species with large
      population sizes, such as many insect species, may be able to invade faster if
      they are polymorphic than if there is only a single morph present in the
      population. 

PMID- 23874462
TI  - Dry-coated live viral vector vaccines delivered by nanopatch microprojections
      retain long-term thermostability and induce transgene-specific T cell responses
      in mice.
AB  - The disadvantages of needle-based immunisation motivate the development of
      simple, low cost, needle-free alternatives. Vaccine delivery to cutaneous
      environments rich in specialised antigen-presenting cells using microprojection
      patches has practical and immunological advantages over conventional needle
      delivery. Additionally, stable coating of vaccine onto microprojections removes
      logistical obstacles presented by the strict requirement for cold-chain storage
      and distribution of liquid vaccine, or lyophilised vaccine plus diluent. These
      attributes make these technologies particularly suitable for delivery of vaccines
      against diseases such as malaria, which exerts its worst effects in countries
      with poorly-resourced healthcare systems. Live viral vectors including
      adenoviruses and poxviruses encoding exogenous antigens have shown significant
      clinical promise as vaccines, due to their ability to generate high numbers of
      antigen-specific T cells. Here, the simian adenovirus serotype 63 and the
      poxvirus modified vaccinia Ankara--two vectors under evaluation for the delivery
      of malaria antigens to humans--were formulated for coating onto Nanopatch
      microprojections and applied to murine skin. Co-formulation with the stabilising
      disaccharides trehalose and sucrose protected virions during the dry-coating
      process. Transgene-specific CD8(+) T cell responses following Nanopatch delivery
      of both vectors were similar to intradermal injection controls after a single
      immunisation (despite a much lower delivered dose), though MVA boosting of pre
      primed responses with Nanopatch was found to be less effective than the ID route.
      Importantly, disaccharide-stabilised ChAd63 could be stored for 10 weeks at 37
      degrees C with less than 1 log10 loss of viability, and retained single-dose
      immunogenicity after storage. These data support the further development of
      microprojection patches for the deployment of live vaccines in hot climates.

PMID- 23874461
TI  - Dendritic cell immunoreceptor is a new target for anti-AIDS drug development:
      identification of DCIR/HIV-1 inhibitors.
AB  - The HIV-1 pandemic continues to expand while no effective vaccine or cure is yet
      available. Existing therapies have managed to limit mortality and control viral
      proliferation, but are associated with side effects, do not cure the disease and
      are subject to development of resistance. Finding new therapeutic targets and
      drugs is therefore crucial. We have previously shown that the dendritic cell
      immunoreceptor (DCIR), a C-type lectin receptor expressed on dendritic cells
      (DCs), acts as an attachment factor for HIV-1 to DCs and contributes to HIV-1
      transmission to CD4(+) T lymphocytes (CD4TL). Directly involved in HIV-1
      infection, DCIR is expressed in apoptotic or infected CD4TL and promotes trans
      infection to bystander cells. Here we report the 3D modelling of the
      extracellular domain of DCIR. Based on this structure, two surface accessible
      pockets containing the carbohydrate recognition domain and the EPS binding motif,
      respectively, were targeted for screening of chemicals that will disrupt normal
      interaction with HIV-1 particle. Preliminary screening using Raji-CD4-DCIR cells
      allowed identification of two inhibitors that decreased HIV-1 attachment and
      propagation. The impact of these inhibitors on infection of DCs and CD4TL was
      evaluated as well. The results of this study thus identify novel molecules
      capable of blocking HIV-1 transmission by DCs and CD4TL. 

PMID- 23874463
TI  - Molecular organization of the nanoscale surface structures of the dragonfly
      Hemianax papuensis wing epicuticle.
AB  - The molecular organization of the epicuticle (the outermost layer) of insect
      wings is vital in the formation of the nanoscale surface patterns that are
      responsible for bestowing remarkable functional properties. Using a combination
      of spectroscopic and chromatographic techniques, including Synchrotron-sourced
      Fourier-transform infrared microspectroscopy (FTIR), x-ray photoelectron
      spectroscopy (XPS) depth profiling and gas chromatography-mass spectrometry
      (GCMS), we have identified the chemical components that constitute the nanoscale
      structures on the surface of the wings of the dragonfly, Hemianax papuensis. The
      major components were identified to be fatty acids, predominantly hexadecanoic
      acid and octadecanoic acid, and n-alkanes with even numbered carbon chains
      ranging from C14 to C30. The data obtained from XPS depth profiling, in
      conjunction with that obtained from GCMS analyses, enabled the location of
      particular classes of compounds to different regions within the epicuticle.
      Hexadecanoic acid was found to be a major component of the outer region of the
      epicuticle, which forms the surface nanostructures, and was also detected in
      deeper layers along with octadecanoic acid. Aliphatic compounds were detected
      throughout the epicuticle, and these appeared to form a third discrete layer that
      was separate from both the inner and outer epicuticles, which has never
      previously been reported. 

PMID- 23874464
TI  - Zoledronic acid enhances lipopolysaccharide-stimulated proinflammatory reactions
      through controlled expression of SOCS1 in macrophages.
AB  - Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect
      of nitrogen-containing bisphosphonate (NBP) use. Many studies have shown that
      BRONJ is limited to the jawbone and does not occur in the other bones. We
      hypothesized that BRONJ is related to local bacterial iections and involves the
      innate immune system. To examine the relationship between BRONJ and innate
      immunity, we examined the effects of NBPs on macrophages, one of the important
      cell types in innate immunity. The expression of toll-like receptor-4 (TLR4) in
      cells after pretreatment with zoledronic acid (ZOL) did not considerably differ
      from that in untreated control cells. However, cytokine levels and nitric oxide
      (NO) production increased after pretreatment with ZOL. Furthermore, ZOL induced
      NF-kappaB activation by enhancing IkappaB-alpha degradation. Lipopolysaccharide
      (LPS)-induced apoptosis also increased after pretreatment with ZOL. This effect
      was mediated by a reduction of suppressor of cytokine signaling-1 (SOCS1), which
      is a negative regulator of myeloid differentiation primary response gene 88 (MyD
      88)-dependent signaling. These results suggest that ZOL induced excessive innate
      immune response and proinflammatory cytokine production and that these processes
      may be involved in the bone destruction observed in BRONJ. 

PMID- 23874465
TI  - Volunteer bias in recruitment, retention, and blood sample donation in a
      randomised controlled trial involving mothers and their children at six months
      and two years: a longitudinal analysis.
AB  - BACKGROUND: The vulnerability of clinical trials to volunteer bias is under
      reported. Volunteer bias is systematic error due to differences between those who
      choose to participate in studies and those who do not. METHODS AND RESULTS: This
      paper extends the applications of the concept of volunteer bias by using data
      from a trial of probiotic supplementation for childhood atopy in healthy dyads to
      explore 1) differences between a) trial participants and aggregated data from
      publicly available databases b) participants and non-participants as the trial
      progressed 2) impact on trial findings of weighting data according to deprivation
      (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454)
      were less deprived than the target population, matched for area of residence and
      delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and
      0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed,
      representation of the most deprived decreased. These participants and smokers
      were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and
      0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28
      1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57
      0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or
      reporting infants' adverse events or rashes were more likely to attend research
      clinics and consent to skin-prick testing. Mothers participating to help children
      were more likely to consent to infant blood sample donation. 2) In one trial
      outcome, atopic eczema, the intervention had a positive effect only in the over
      represented, least deprived group. Here, data weighting attenuated risk reduction
      from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to
      0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for
      volunteer bias intensified during the trial, due to non-participation of the most
      deprived and smokers. However, these were not the only predictors of non
      participation. Data weighting quantified volunteer bias and modified one
      important trial outcome. TRIAL REGISTRATION: This randomised, double blind,
      parallel group, placebo controlled trial is registered with the International
      Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422.
      Registered title: Probiotics in the prevention of atopy in infants and children.

PMID- 23874466
TI  - Probing the frontostriatal loops involved in executive and limbic processing via
      interleaved TMS and functional MRI at two prefrontal locations: a pilot study.
AB  - BACKGROUND: The prefrontal cortex (PFC) is an anatomically and functionally
      heterogeneous area which influences cognitive and limbic processing through
      connectivity to subcortical targets. As proposed by Alexander et al. (1986) the
      lateral and medial aspects of the PFC project to distinct areas of the striatum
      in parallel but functionally distinct circuits. The purpose of this preliminary
      study was to determine if we could differentially and consistently activate these
      lateral and medial cortical-subcortical circuits involved in executive and limbic
      processing though interleaved transcranial magnetic stimulation (TMS) in the MR
      environment. METHODS: Seventeen healthy individuals received interleaved TMS-BOLD
      imaging with the coil positioned over the dorsolateral (EEG: F3) and ventromedial
      PFC (EEG: FP1). BOLD signal change was calculated in the areas directly
      stimulated by the coil and in subcortical regions with afferent and efferent
      connectivity to the TMS target areas. Additionally, five individuals were tested
      on two occasions to determine test-retest reliability. RESULTS: Region of
      interest analysis revealed that TMS at both prefrontal sites led to significant
      BOLD signal increases in the cortex under the coil, in the striatum, and the
      thalamus, but not in the visual cortex (negative control region). There was a
      significantly larger BOLD signal change in the caudate following medial PFC TMS,
      relative to lateral TMS. The hippocampus in contrast was significantly more
      activated by lateral TMS. Post-hoc voxel-based analysis revealed that within the
      caudate the location of peak activity was in the ventral caudate following medial
      TMS and the dorsal caudate following lateral TMS. Test-retest reliability data
      revealed consistent BOLD responses to TMS within each individual but a large
      variation between individuals. CONCLUSION: These data demonstrate that, through
      an optimized TMS/BOLD sequence over two unique prefrontal targets, it is possible
      to selectively interrogate the patency of these established cortical-subcortical
      networks in healthy individuals, and potentially patient populations.

PMID- 23874467
TI  - High levels of both n-3 and n-6 long-chain polyunsaturated fatty acids in cord
      serum phospholipids predict allergy development.
AB  - BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell
      activation and dampen inflammation. They might thereby counteract the neonatal
      immune activation and hamper normal tolerance development to harmless
      environmental antigens. We investigated whether fatty acid composition of cord
      serum phospholipids affects allergy development up to age 13 years. METHODS: From
      a population-based birth-cohort born in 1996/7 and followed until 13 years of age
      (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy
      (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on
      diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from
      cases and controls were analysed for proportions of saturated, monounsaturated
      and polyunsaturated fatty acids among serum phospholipids. RESULTS: The cord
      serum phospholipids from subject who later developed either respiratory allergy
      or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as
      well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord
      serum phospholipids from controls who did not develop allergy (P<0.001 for all
      comparisons). Conversely, individuals later developing allergy had lower
      proportion of the monounsaturated fatty acid 18?1n-9 as well as total MUFA
      (p<0.001) among cord serum phospholipids. The risk of respiratory allergy at age
      13 increased linearly with the proportion of n-3 LCPUFA (Ptrend<0.001), n-6
      LCPUFA (Ptrend = 0.001), and total LCPUFA (Ptrend<0.001) and decreased linearly
      with the proportions of total MUFA (Ptrend = 0.025) in cord serum phospholipids.
      Furthermore, Kaplan-Meier estimates of allergy development demonstrated that
      total LCPUFA proportion in cord serum phospholipids was significantly associated
      with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control
      for sex and parental allergy. CONCLUSION: A high proportion of long-chain PUFAs
      among cord serum phospholipids may predispose to allergy development. The
      mechanism is unknown, but may involve dampening of the physiologic immune
      activation in infancy needed for proper maturation of the infant's immune system.

PMID- 23874468
TI  - Sleep, school performance, and a school-based intervention among school-aged
      children: a sleep series study in China.
AB  - BACKGROUND: Sufficient sleep during childhood is essential to ensure a transition
      into a healthy adulthood. However, chronic sleep loss continues to increase
      worldwide. In this context, it is imperative to make sleep a high-priority and
      take action to promote sleep health among children. The present series of studies
      aimed to shed light on sleep patterns, on the longitudinal association of sleep
      with school performance, and on practical intervention strategy for Chinese
      school-aged children. METHODS AND FINDINGS: A serial sleep researches, including
      a national cross-sectional survey, a prospective cohort study, and a school-based
      sleep intervention, were conducted in China from November 2005 through December
      2009. The national cross-sectional survey was conducted in 8 cities and a random
      sample of 20,778 children aged 9.0+/-1.61 years participated in the survey. The
      five-year prospective cohort study included 612 children aged 6.8+/-0.31 years.
      The comparative cross-sectional study (baseline: n = 525, aged 10.80+/-0.41; post
      intervention follow-up: n = 553, aged 10.81+/-0.33) was undertaken in 6 primary
      schools in Shanghai. A battery of parent and teacher reported questionnaires were
      used to collect information on children's sleep behaviors, school performance,
      and sociodemographic characteristics. The mean sleep duration was 9.35+/-0.77
      hours. The prevalence of daytime sleepiness was 64.4% (sometimes: 37.50%;
      frequently: 26.94%). Daytime sleepiness was significantly associated with
      impaired attention, learning motivation, and particularly, academic achievement.
      By contrast, short sleep duration only related to impaired academic achievement.
      After delaying school start time 30 minutes and 60 minutes, respectively, sleep
      duration correspondingly increased by 15.6 minutes and 22.8 minutes,
      respectively. Moreover, intervention significantly improved the sleep duration
      and daytime sleepiness. CONCLUSIONS: Insufficient sleep and daytime sleepiness
      commonly existed and positively associated with the impairment of school
      performance, especially academic achievement, among Chinese school-aged children.
      The effectiveness of delaying school staring time emphasized the benefits of
      optimal school schedule regulation to children's sleep health.

PMID- 23874469
TI  - Activating and relaxing music entrains the speed of beat synchronized walking.
AB  - Inspired by a theory of embodied music cognition, we investigate whether music
      can entrain the speed of beat synchronized walking. If human walking is in
      synchrony with the beat and all musical stimuli have the same duration and the
      same tempo, then differences in walking speed can only be the result of music
      induced differences in stride length, thus reflecting the vigor or physical
      strength of the movement. Participants walked in an open field in synchrony with
      the beat of 52 different musical stimuli all having a tempo of 130 beats per
      minute and a meter of 4 beats. The walking speed was measured as the walked
      distance during a time interval of 30 seconds. The results reveal that some music
      is 'activating' in the sense that it increases the speed, and some music is
      'relaxing' in the sense that it decreases the speed, compared to the spontaneous
      walked speed in response to metronome stimuli. Participants are consistent in
      their observation of qualitative differences between the relaxing and activating
      musical stimuli. Using regression analysis, it was possible to set up a
      predictive model using only four sonic features that explain 60% of the variance.
      The sonic features capture variation in loudness and pitch patterns at periods of
      three, four and six beats, suggesting that expressive patterns in music are
      responsible for the effect. The mechanism may be attributed to an attentional
      shift, a subliminal audio-motor entrainment mechanism, or an arousal effect, but
      further study is needed to figure this out. Overall, the study supports the
      hypothesis that recurrent patterns of fluctuation affecting the binary meter
      strength of the music may entrain the vigor of the movement. The study opens up
      new perspectives for understanding the relationship between entrainment and
      expressiveness, with the possibility to develop applications that can be used in
      domains such as sports and physical rehabilitation. 

PMID- 23874470
TI  - Incident angle of saltating particles in wind-blown sand.
AB  - Incident angle of saltating particles plays a very important role in aeolian
      events. In this paper, the incident angles of sand particles near the sand bed
      were measured in wind tunnel. It reveals that the incident angles range widely
      from 0 degrees  to 180 degrees  and thereby the means of angles are larger than
      published data. Surprisingly, it is found the proportion that angles of 5 degrees
      -15 degrees  occupy is far below previous reports. The measuring height is
      probably the most important reason for the measurement differences between this
      study and previous investigations. 

PMID- 23874471
TI  - CT coronary angiography is feasible for the assessment of coronary artery disease
      in chronic dialysis patients, despite high average calcium scores.
AB  - PURPOSE: Significant obstructive coronary artery disease (CAD) is common in
      asymptomatic dialysis patients. Identifying these high risk patients is warranted
      and may improve the prognosis of this vulnerable patient group. Routine
      catheterization of incident dialysis patients has been proposed, but is
      considered too invasive. CT-angiography may therefore be more appropriate.
      However, extensive coronary calcification, often present in this patient group,
      might hamper adequate lumen evaluation. The objective of this study was to assess
      the feasibility of CT-angiography in this patient group. METHODS: For this
      analysis all patients currently participating in the ICD2 trial (ISRCTN20479861),
      with no history of PCI or CABG were included. The major epicardial vessels were
      evaluated on a segment basis (segment 1-3, 5-8, 11 and 13) by a team consisting
      of an interventional and an imaging specialist. Segments were scored as not
      significant, significant and not interpretable. RESULTS: A total of 70 dialysis
      patients, with a mean age of 66+/-8 yrs and predominantly male (70%) were
      included. The median calcium score was 623 [79, 1619]. Over 90% of the analyzed
      segments were considered interpretable. The incidence of significant CAD on CT
      was 43% and was associated with cardiovascular events during follow-up. The
      incidence of cardiovascular events after 2-years follow-up: 36% vs. 0% in
      patients with no significant CAD (p<0.01). CONCLUSION: Despite the high calcium
      scores CT-angiography is feasible for the evaluation of the extent of CAD in
      dialysis patients. Moreover the presence of significant CAD on CT was associated
      with events during follow-up.

PMID- 23874473
TI  - The combined influence of distance and neighbourhood deprivation on Emergency
      Department attendance in a large English population: a retrospective database
      study.
AB  - The frequency of visits to Emergency Departments (ED) varies greatly between
      populations. This may reflect variation in patient behaviour, need,
      accessibility, and service configuration as well as the complex interactions
      between these factors. This study investigates the relationship between distance,
      socio-economic deprivation, and proximity to an alternative care setting (a Minor
      Injuries Unit (MIU)), with particular attention to the interaction between
      distance and deprivation. It is set in a population of approximately 5.4 million
      living in central England, which is highly heterogeneous in terms of ethnicity,
      socio-economics, and distance to hospital. The study data set captured 1,413,363
      ED visits made by residents of the region to National Health Service (NHS)
      hospitals during the financial year 2007/8. Our units of analysis were small
      units of census geography having an average population of 1,545. Separate
      regression models were made for children and adults. For each additional
      kilometre of distance from a hospital, predicted child attendances fell by 2.2%
      (1.7%-2.6% p<0.001) and predicted adult attendances fell by 1.5% (1.2% -1.8%,
      p<0.001). Compared to the least deprived quintile, attendances in the most
      deprived quintile more than doubled for children (incident rate ratio (IRR) =
      2.19, (1.90-2.54, p<0.001)) and adults (IRR 2.26, (2.01-2.55, p<0.001)).
      Proximity of an MIU was significant and both adult and child attendances were
      greater in populations who lived further away from them, suggesting that MIUs may
      reduce ED demand. The interaction between distance and deprivation was
      significant. Attendance in deprived neighbourhoods reduces with distance to a
      greater degree than in less deprived ones for both adults and children. In
      conclusion, ED use is related to both deprivation and distance, but the effect of
      distance is modified by deprivation.

PMID- 23874472
TI  - Porcine adipose tissue-derived mesenchymal stem cells retain their proliferative
      characteristics, senescence, karyotype and plasticity after long-term
      cryopreservation.
AB  - We and others have provided evidence that adipose tissue-derived mesenchymal stem
      cells (ASCs) can mitigate rat cardiac functional deterioration after myocardial
      ischemia, even though the mechanism of action or the relevance of these findings
      to human conditions remains elusive. In this regard, the porcine model is a key
      translational step, because it displays heart anatomic-physiological features
      that are similar to those found in the human heart. Towards this end, we wanted
      to establish the cultural characteristics of porcine ASCs (pASCs) with or without
      long-term cryostorage, considering that allogeneic transplantation may also be a
      future option. Compared to fresh pASCs, thawed cells displayed 90-95% viability
      and no changes in morphological characteristics or in the expression of surface
      markers (being pASCs characterized by positive markers CD29(+); CD90(+); CD44(+);
      CD140b(+); CD105(+); and negative markers CD31(-); CD34(-); CD45(-) and SLA-DR(
      ); n = 3). Mean population doubling time was also comparable (64.26+/-15.11 hours
      to thawed cells vs. 62.74+/-18.07 hours to fresh cells) and cumulative population
      doubling increased constantly until Passage 10 (P10) in the entire cell
      population, with a small and gradual increase in senescence (P5, 3.25%+/-0.26 vs.
      3.47%+/-0.32 and P10, 9.6%+/-0.29 vs. 10.67%+/-1.25, thawed vs. fresh; SA-beta
      Gal staining). Chromosomal aberrations were not observed. In addition, under both
      conditions pASCs responded to adipogenic and osteogenic chemical cues in vitro.
      In conclusion, we have demonstrated the growth characteristics, senescence, and
      the capacity of pASCs to respond to chemical cues in vitro and have provided
      evidence that these properties are not influenced by cryostorage in 10% DMSO
      solution. 

PMID- 23874474
TI  - Evaluation of estrogenic activity of licorice species in comparison with hops
      used in botanicals for menopausal symptoms.
AB  - The increased cancer risk associated with hormone therapies has encouraged many
      women to seek non-hormonal alternatives including botanical supplements such as
      hops (Humulus lupulus) and licorice (Glycyrrhiza spec.) to manage menopausal
      symptoms. Previous studies have shown estrogenic properties for hops, likely due
      to the presence of 8-prenylnarigenin, and chemopreventive effects mainly
      attributed to xanthohumol. Similarly, a combination of estrogenic and
      chemopreventive properties has been reported for various Glycyrrhiza species. The
      major goal of the current study was to evaluate the potential estrogenic effects
      of three licorice species (Glycyrrhiza glabra, G. uralensis, and G. inflata) in
      comparison with hops. Extracts of Glycyrrhiza species and spent hops induced
      estrogen responsive alkaline phosphatase activity in endometrial cancer cells,
      estrogen responsive element (ERE)-luciferase in MCF-7 cells, and Tff1 mRNA in
      T47D cells. The estrogenic activity decreased in the order H. lupulus > G.
      uralensis > G. inflata > G. glabra. Liquiritigenin was found to be the principle
      phytoestrogen of the licorice extracts; however, it exhibited lower estrogenic
      effects compared to 8-prenylnaringenin in functional assays. Isoliquiritigenin,
      the precursor chalcone of liquiritigenin, demonstrated significant estrogenic
      activities while xanthohumol, a metabolic precursor of 8-prenylnaringenin, was
      not estrogenic. Liquiritigenin showed ERbeta selectivity in competitive binding
      assay and isoliquiritigenin was equipotent for ER subtypes. The estrogenic
      activity of isoliquiritigenin could be the result of its cyclization to
      liquiritigenin under physiological conditions. 8-Prenylnaringenin had nanomolar
      estrogenic potency without ER selectivity while xanthohumol did not bind ERs.
      These data demonstrated that Glycyrrhiza species with different contents of
      liquiritigenin have various levels of estrogenic activities, suggesting the
      importance of precise labeling of botanical supplements. Although hops shows
      strong estrogenic properties via ERalpha, licorice might have different
      estrogenic activities due to its ERbeta selectivity, partial estrogen agonist
      activity, and non-enzymatic conversion of isoliquiritigenin to liquiritigenin. 

PMID- 23874475
TI  - Characteristics of latrines in central Tanzania and their relation to fly
      catches.
AB  - The disposal of human excreta in latrines is an important step in reducing the
      transmission of diarrhoeal diseases. However, in latrines, flies can access the
      latrine contents and serve as a mechanical transmitter of diarrhoeal pathogens.
      Furthermore, the latrine contents can be used as a breeding site for flies, which
      may further contribute to disease transmission. Latrines do not all produce
      flies, and there are some which produce only a few, while others can produce
      thousands. In order to understand the role of the latrine in determining this
      productivity, a pilot study was conducted, in which fifty latrines were observed
      in and around Ifakara, Tanzania. The characteristics of the latrine
      superstructure, use of the latrine, and chemical characteristics of pit latrine
      contents were compared to the numbers of flies collected in an exit trap placed
      over the drop hole in the latrine. Absence of a roof was found to have a
      significant positive association (t=3.17, p=0.003) with the total number of flies
      collected, and temporary superstructures, particularly as opposed to brick
      superstructures (z=4.26, p<0.001), and increased total solids in pit latrines
      (z=2.57, p=0.01) were significantly associated with increased numbers of
      blowflies leaving the latrine. The number of larvae per gram was significantly
      associated with the village from which samples were taken, with the largest
      difference between two villages outside Ifakara (z=2.12, p=0.03). The effect of
      latrine superstructure (roof, walls) on fly production may indicate that
      improvements in latrine construction could result in decreases in fly populations
      in areas where they transmit diarrhoeal pathogens. 

PMID- 23874476
TI  - Blood neutrophil counts in HIV-infected patients with pulmonary tuberculosis:
      association with sputum mycobacterial load.
AB  - BACKGROUND: Increasing evidence suggests that neutrophils play a role in the host
      response to Mycobacterium tuberculosis. We determined whether neutrophil counts
      in peripheral blood are associated with tuberculosis (TB) and with mycobacterial
      load in sputum in HIV-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Adults
      enrolling in an antiretroviral treatment (ART) clinic in a Cape Town township
      were screened for TB regardless of symptoms. Paired sputum samples were examined
      using liquid culture, fluorescence microscopy, and the Xpert MTB/RIF assay.
      Absolute neutrophil counts (ANC) were measured in blood samples. Of 602 HIV
      infected patients screened, 523 produced one or more sputum samples and had
      complete results available for analysis. Among these 523 patients, the median CD4
      count was 169*10(9)/L (IQR, 96-232) and median ANC was 2.6*10(9)/L (IQR, 1.9
      3.6). Culture-positive pulmonary tuberculosis was diagnosed in 89 patients.
      Patients with TB had a median ANC of 3.4*10(9)/L (IQR, 2.4-5.1) compared to
      2.5*10(9)/L (IQR, 1.8-3.4) among those who were culture negative (p<0.0001). In
      multivariable analyses, having pulmonary TB was associated with an adjusted risk
      ratio (aRR) of 2.6 (95%CI, 1.5-4.5) for having an ANC level that exceeded the
      median value (ANC >=2.6*10(9)/L; p = 0.0006) and an aRR of 6.8 (95%CI, 2.3-20.4)
      for having neutrophilia defined by a neutrophil count exceeding the upper limit
      of the normal range (ANC >7.5*10(9)/L; p = 0.0005). Patients were then classified
      into four mutually exclusive groups with increasing sputum mycobacterial load as
      defined by the results of culture, Xpert MTB/RIF and sputum smear microscopy.
      Multivariable analyses demonstrated that increasing sputum mycobacterial load was
      positively associated with blood ANC >=2.6*10(9)/L and with neutrophilia.
      CONCLUSIONS/SIGNIFICANCE: Increased blood neutrophil counts were independently
      associated with pulmonary TB and sputum mycobacterial burden in this HIV-infected
      patient group. This observation supports the growing body of literature regarding
      the potential role for neutrophils in the host response to TB.

PMID- 23874477
TI  - Activation of human stearoyl-coenzyme A desaturase 1 contributes to the lipogenic
      effect of PXR in HepG2 cells.
AB  - The pregnane X receptor (PXR) was previously known as a xenobiotic receptor.
      Several recent studies suggested that PXR also played an important role in lipid
      homeostasis but the underlying mechanism remains to be clearly defined. In this
      study, we found that rifampicin, an agonist of human PXR, induced lipid
      accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level
      increased. However, the free cholesterol and triglyceride levels were not
      changed. Treatment of HepG2 cells with rifampicin induced the expression of the
      free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes,
      including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase
      (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of
      acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over
      expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher
      than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of
      PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2
      cells. Promoter analysis showed that the human SCD1 gene promoter is activated by
      PXR and a novel DR-7 type PXR response element (PXRE) response element was
      located at -338 bp of the SCD1 gene promoter. Taken together, these results
      indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is
      a novel PXR target gene. 

PMID- 23874478
TI  - Heat shock protein 70 acts as a potential biomarker for early diagnosis of heart
      failure.
AB  - Early identification for heart failure (HF) may be useful for disease modifying
      treatment in order to reduce heart disease progression or even to reverse it. In
      our previous studies, we have revealed a group of heat shock proteins (HSPs)
      which might be related to neonatal rat cardiomyocyte hypertrophy by proteomic
      approach. Here, we confirm that HSPs, including HSP27 and HSP70, altered in the
      early stage of cardiac remodeling in vivo animal model. Furthermore, plasma
      concentrations of those HSPs and their potential screening value were evaluated
      at different stages in 222 patient subjects. Plasma HSP27, HSP70 and HSP90 were
      measured using enzyme-linked immunosorbent assay. Results indicate that HSP70 was
      positively correlated to the severity (progression) of HF (r = 0.456, p<0.001).
      The area under the rate of change (ROC) curve was 0.601 (p = 0.017) in patients
      with stage B HF and 0.835 (p<0.001) in those with stage C HF. However, HSP27 and
      HSP90 did not display significant changes in any stage of HF in this study. Taken
      together, plasma concentrations of HSP70 elevated with the progression of HF and
      might act as a potential screening biomarker for early diagnosis of HF. 

PMID- 23874479
TI  - Diversity of Eastern North American ant communities along environmental
      gradients.
AB  - Studies of species diversity patterns across regional environmental gradients
      seldom consider the impact of habitat type on within-site (alpha) and between
      site (beta) diversity. This study is designed to identify the influence of
      habitat type across geographic and environmental space, on local patterns of
      species richness and regional turnover patterns of ant diversity in the
      northeastern United States. Specifically, I aim to 1) compare local species
      richness in paired open and forested transects and identify the environmental
      variables that best correlate with richness; and 2) document patterns of beta
      diversity throughout the region in both open and forested habitat. I
      systematically sampled ants at 67 sites from May to August 2010, spanning 10
      degrees of latitude, and 1000 meters of elevation. Patterns of alpha and beta
      diversity across the region and along environmental gradients differed between
      forested and open habitats. Local species richness was higher in the low
      elevation and warmest sites and was always higher in open habitat than in forest
      habitat transects. Richness decreased as temperature decreased or elevation
      increased. Forested transects show strong patterns of decreasing dissimilarity in
      species composition between sites along the temperature gradient but open habitat
      transects did not. Maximum temperature of the warmest month better predicted
      species richness than either latitude or elevation. I find that using
      environmental variables as key predictors of richness yields more biologically
      relevant results, and produces simpler macroecological models than commonly used
      models which use only latitude and elevation as predictors of richness and
      diversity patterns. This study contributes to the understanding of mechanisms
      that structure the communities of important terrestrial arthropods which are
      likely to be influenced by climatic change. 

PMID- 23874480
TI  - Vibrio coralliilyticus search patterns across an oxygen gradient.
AB  - The coral pathogen, Vibrio coralliilyticus shows specific chemotactic search
      pattern preference for oxic and anoxic conditions, with the newly identified 3
      step flick search pattern dominating the patterns used in oxic conditions. We
      analyzed motile V. coralliilyticus cells for behavioral changes with varying
      oxygen concentrations to mimic the natural coral environment exhibited during
      light and dark conditions. Results showed that 3-step flicks were 1.4* (P =
      0.006) more likely to occur in oxic conditions than anoxic conditions with mean
      values of 18 flicks (95% CI = 0.4, n = 53) identified in oxic regions compared to
      13 (95% CI = 0.5, n = 38) at anoxic areas. In contrast, run and reverse search
      patterns were more frequent in anoxic regions with a mean value of 15 (95% CI =
      0.7, n = 46), compared to a mean value of 10 (95% CI = 0.8, n = 29) at oxic
      regions. Straight swimming search patterns remained similar across oxic and
      anoxic regions with a mean value of 13 (95% CI = 0.7, n = oxic: 13, anoxic: 14).
      V. coralliilyticus remained motile in oxic and anoxic conditions, however, the 3
      step flick search pattern occurred in oxic conditions. This result provides an
      approach to further investigate the 3-step flick. 

PMID- 23874481
TI  - Elevated snail expression mediates tumor progression in areca quid chewing
      associated oral squamous cell carcinoma via reactive oxygen species.
AB  - BACKGROUND: Snail is an important transcription factor implicated in several
      tumor progression and can be induced by reactive oxygen species (ROS). Areca quid
      chewing is a major risk factor of oral squamous cell carcinoma (OSCC). Therefore,
      we hypothesize that the major areca nut alkaloid arecoline may induce Snail via
      ROS and involve in the pathogenesis of areca quid chewing-associated OSCC.
      METHODOLOGY/PRINCIPAL FINDING: Thirty-six OSCC and ten normal oral epithelium
      specimens were examined by immunohistochemistry and analyzed by the clinico
      pathological profiles. Cytotoxicity, 2', 7'-dichlorofluorescein diacetate assay,
      and western blot were used to investigate the effects of arecoline in human oral
      keratinocytes (HOKs) and oral epithelial cell line OECM-1 cells. In addition,
      antioxidants N-acetyl-L-cysteine (NAC), curcumin, and epigallocatechin-3 gallate
      (EGCG) were added to find the possible regulatory mechanisms. Initially, Snail
      expression was significantly higher in OSCC specimens (p<0.05). Elevated Snail
      expression was associated with lymph node metastasis (p = 0.031) and poor
      differentiation (p = 0.017). Arecoline enhanced the generation of intracellular
      ROS at the concentration higher than 40 ug/ml (p<0.05). Arecoline was also found
      to induced Snail expression in a dose- and time-dependent manner (p<0.05).
      Treatment with NAC, curcumin, and EGCG markedly inhibited arecoline induced Snail
      expression (p<0.05). CONCLUSION/SIGNIFICANCE: Our results suggest that Snail
      overexpression in areca quid chewing-associated OSCC is associated with tumors
      differentiation and lymph node metastasis. Arecoline-upregulated Snail expression
      may be mediated by ROS generation. In addition, arecoline induced Snail
      expression was downregulated by NAC, curcumin, and EGCG.

PMID- 23874482
TI  - Dissociation between dorsal and ventral posterior parietal cortical responses to
      incidental changes in natural scenes.
AB  - BACKGROUND: The posterior parietal cortex (PPC) is thought to interact with the
      medial temporal lobe (MTL) to support spatial cognition and topographical memory.
      While the response of medial temporal lobe regions to topographical stimuli has
      been intensively studied, much less research has focused on the role of PPC and
      its functional connectivity with the medial temporal lobe. METHODOLOGY/PRINCIPLE
      FINDINGS: Here we report a dissociation between dorsal and ventral regions of PPC
      in response to different types of change in natural scenes using an fMRI
      adaptation paradigm. During scanning subjects performed an incidental target
      detection task whilst viewing trial unique sequentially presented pairs of
      natural scenes, each containing a single prominent object. We observed a
      dissociation between the superior parietal gyrus and the angular gyrus, with the
      former showing greater sensitivity to spatial change, and the latter showing
      greater sensitivity to scene novelty. In addition, we observed that the
      parahippocampal cortex has increased functional connectivity with the angular
      gyrus, but not superior parietal gyrus, when subjects view change to the scene
      content. CONCLUSIONS/SIGNIFICANCE: Our findings provide support for proposed
      dissociations between dorsal and ventral regions of PPC and suggest that the
      dorsal PPC may support the spatial coding of the visual environment even when
      this information is incidental to the task at hand. Further, through revealing
      the differential functional interactions of the SPG and AG with the MTL our
      results help advance our understanding of how the MTL and PPC cooperate to update
      representations of the world around us.

PMID- 23874483
TI  - beta5 integrin up-regulation in brain-derived neurotrophic factor promotes cell
      motility in human chondrosarcoma.
AB  - Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to
      invade locally and cause distant metastasis; it has a poor prognosis and shows a
      predilection for metastasis to the lungs. Brain derived neurotrophic factor
      (BDNF) is a small-molecule protein from the neurotrophin family of growth factors
      that is associated with the disease status and outcomes of cancers. However, the
      effect of BDNF on migration activity in human chondrosarcoma cells is mostly
      unknown. Here, we found that human chondrosarcoma tissues showed significant
      expression of BDNF, which was higher than that in normal cartilage and primary
      chondrocytes. We also found that BDNF increased the migration and expression of
      beta5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF
      expression markedly inhibited migratory activity. BDNF-mediated migration and
      beta5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA
      against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt,
      and NF-kappaB inhibitors or mutants also abolished BDNF-promoted migration and
      integrin expression. The PI3K, Akt, and NF-kappaB signaling pathway was activated
      after BDNF treatment. Taken together, our results indicate that BDNF enhances the
      migration of chondrosarcoma by increasing beta5 integrin expression through a
      signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF
      kappaB. BDNF thus represents a promising new target for treating chondrosarcoma
      metastasis. 

PMID- 23874484
TI  - SMETANA: accurate and scalable algorithm for probabilistic alignment of large
      scale biological networks.
AB  - In this paper we introduce an efficient algorithm for alignment of multiple large
      scale biological networks. In this scheme, we first compute a probabilistic
      similarity measure between nodes that belong to different networks using a semi
      Markov random walk model. The estimated probabilities are further enhanced by
      incorporating the local and the cross-species network similarity information
      through the use of two different types of probabilistic consistency
      transformations. The transformed alignment probabilities are used to predict the
      alignment of multiple networks based on a greedy approach. We demonstrate that
      the proposed algorithm, called SMETANA, outperforms many state-of-the-art network
      alignment techniques, in terms of computational efficiency, alignment accuracy,
      and scalability. Our experiments show that SMETANA can easily align tens of
      genome-scale networks with thousands of nodes on a personal computer without any
      difficulty. The source code of SMETANA is available upon request. The source code
      of SMETANA can be downloaded from http://www.ece.tamu.edu/~bjyoon/SMETANA/. 

PMID- 23874485
TI  - Characterization of Ixophilin, a thrombin inhibitor from the gut of Ixodes
      scapularis.
AB  - Ixodes scapularis, the black-legged tick, vectors several human pathogens
      including Borrelia burgdorferi, the agent of Lyme disease in North America.
      Pathogen transmission to the vertebrate host occurs when infected ticks feed on
      the mammalian host to obtain a blood meal. Efforts to understand how the tick
      confronts host hemostatic mechanisms and imbibes a fluid blood meal have largely
      focused on the anticoagulation strategies of tick saliva. The blood meal that
      enters the tick gut remains in a fluid state for several days during the process
      of feeding, and the role of the tick gut in maintaining the blood-meal fluid is
      not understood. We now demonstrate that the tick gut produces a potent inhibitor
      of thrombin, a key enzyme in the mammalian coagulation cascade. Chromatographic
      fractionation of engorged tick gut proteins identified one predominant thrombin
      inhibitory activity associated with an approximately 18 kDa protein, henceforth
      referred to as Ixophilin. The ixophilin gene was preferentially transcribed in
      the guts of feeding nymphs. Expression began after 24 hours of feeding,
      coincident with the flow of host blood into the tick gut. Immunity against
      Ixophilin delayed tick feeding, and decreased feeding efficiency significantly.
      Surprisingly, immunity against Ixophilin resulted in increased Borrelia
      burgdorferi transmission to the host, possibly due to delayed feeding and
      increased transmission opportunity. These observations illuminate the potential
      drawbacks of targeting individual tick proteins in a functional suite. They also
      underscore the need to identify the "anticoagulome" of the tick gut, and to
      prioritize a critical subset of anticoagulants that could be targeted to
      efficiently thwart tick feeding, and block pathogen transmission to the
      vertebrate host. 

PMID- 23874486
TI  - Colorectal cancer patients with low abundance of KRAS mutation may benefit from
      EGFR antibody therapy.
AB  - Epidermal growth factor receptor monoclonal antibody was approved for treatment
      of metastatic colorectal cancer patients carrying KRAS wild type DNA. However,
      recent studies showed that patients with KRAS G13D mutation may benefit from EGFR
      antibody therapy. In this study we tried to explore whether the abundance of KRAS
      mutation could affect the efficacy of EGFR antibody therapy. We firstly
      established a PNA-PCR method which could calculate the percentage of KRAS
      mutation in total DNA and proved its ability on 47 colorectal cancer samples
      bearing KRAS mutations. Then we analyzed the correlation between the abundance of
      KRAS mutations and efficacy of EGFR antibody therapy in another 35 metastatic
      colorectal cancer patients. We proved that PNA-PCR assay could calculate the
      abundance of KRAS mutation and the percentage of mutant DNA in tumor cells varied
      a lot (10.8%~98.3%) on the 47 colorectal cancer patients. The efficacy of EGFR
      antibody correlated with the abundance of KRAS mutations: in the KRAS mutation
      less than 30% group, the disease control rate was 44.4% (4/9); the disease
      control rate of 30~80% group was 5.6% (1/18) and the >80% group was 12.5% (1/8)
      (P = 0.038). In summary, our study showed that PNA-PCR method could easily detect
      the percentage of KRAS mutation in tumor cells and colorectal cancer patients
      with low abundance of KRAS mutation might benefit from EGFR antibody therapy. 

PMID- 23874487
TI  - Headcase promotes cell survival and niche maintenance in the Drosophila testis.
AB  - At the apical tip of the Drosophila testis, germline and somatic stem cells
      surround a cluster of somatic cells called the hub. Hub cells produce a self
      renewal factor, Unpaired (Upd), that activates the JAK-STAT pathway in adjacent
      stem cells to regulate stem cell behavior. Therefore, apical hub cells are a
      critical component of the stem cell niche in the testis. In the course of a
      screen to identify factors involved in regulating hub maintenance, we identified
      headcase (hdc). Hub cells depleted for hdc undergo programmed cell death,
      suggesting that anti-apoptotic pathways play an important role in maintenance of
      the niche. Using hdc as paradigm, we describe here the first comprehensive
      analysis on the effects of a progressive niche reduction on the testis stem cell
      pool. Surprisingly, single hub cells remain capable of supporting numerous stem
      cells, indicating that although the size and number of niche support cells
      influence stem cell maintenance, the testis stem cell niche appears to be
      remarkably robust in the its ability to support stem cells after severe damage. 

PMID- 23874488
TI  - Neurodegeneration in drop-dead mutant drosophila melanogaster is associated with
      the respiratory system but not with Hypoxia.
AB  - Mutations in the gene drop-dead (drd) cause diverse phenotypes in adult
      Drosophila melanogaster including early lethality, neurodegeneration, tracheal
      defects, gut dysfunction, reduced body mass, and female sterility. Despite the
      identification of the drd gene itself, the causes of early lethality and
      neurodegeneration in the mutant flies remain unknown. To determine the pattern of
      drd expression associated with the neurodegenerative phenotype, knockdown of drd
      with various Gal4 drivers was performed. Early adult lethality and
      neurodegeneration were observed upon knockdown of drd in the tracheal system with
      two independent insertions of the breathless-Gal4 driver and upon knockdown in
      the tracheal system and elsewhere with the DJ717-Gal4 driver. Surprisingly,
      rescue of drd expression exclusively in the tracheae in otherwise mutant flies
      rescued the neurodegenerative phenotype but not adult lethality. Gut dysfunction,
      as measured by defecation rate, was not rescued in these flies, and gut function
      appeared normal upon tracheal-specific knockdown of drd. Finally, the hypothesis
      that tracheal dysfunction in drd mutants results in hypoxia was tested. Hypoxia
      sensitive reporter transgenes (LDH-Gal4 and LDH-LacZ) were placed on a drd mutant
      background, but enhanced expression of these reporters was not observed. In
      addition, manipulation of drd expression in the tracheae did not affect
      expression of the hypoxia-induced genes LDH, tango, and similar. Overall, these
      results indicate that there are at least two causes of adult lethality in drd
      mutants, that gut dysfunction and neurodegeneration are independent phenotypes,
      and that neurodegeneration is associated with tracheal expression of drd but not
      with hypoxia. 

PMID- 23874489
TI  - Different regulation of physiological and tumor angiogenesis in zebrafish by
      protein kinase D1 (PKD1).
AB  - Protein kinase D isoenzymes (PKDs, Prkds) are serine threonine kinases that
      belong to the CAMK superfamily. PKD1 is expressed in endothelial cells and is a
      major mediator of biological responses downstream of the VEGFRs that are relevant
      for angiogenesis such as endothelial cell migration, proliferation and
      tubulogenesis in vitro. PKDs also play a critical role in tumor development and
      progression, including tumor angiogenesis. However, given the plethora of
      signaling modules that drive angiogenesis, the precise role of PKD1 in both
      physiological and tumor angiogenesis in vivo has not been worked out so far. This
      study aimed at dissecting the contribution of PKD1 to physiological blood vessel
      formation, PKD1 was found to be widely expressed during zebrafish development. As
      far as physiological angiogenesis was concerned, morpholino-based silencing of
      PKD1 expression moderately reduced the formation of the intersomitic vessels and
      the dorsal longitudinal anastomotic vessel in tg(fli1:EGFP) zebrafish. In
      addition, silencing of PKD1 resulted in reduced formation of the parachordal
      lymphangioblasts that serves as a precursor for the developing thoracic duct.
      Interestingly, tumor angiogenesis was completely abolished in PKD1 morphants
      using the zebrafish/tumor xenograft angiogenesis assay. Our data in zebrafish
      demonstrate that PKD1 contributes to the regulation of physiological angiogenesis
      and lymphangiogenesis during zebrafish development and is essential for tumor
      angiogenesis. 

PMID- 23874490
TI  - Passive immunization with hypochlorite-oxLDL specific antibodies reduces plaque
      volume in LDL receptor-deficient mice.
AB  - AIMS: New strategies to overcome complications of cardiovascular diseases are
      needed. Since it has been demonstrated that atherosclerosis is an inflammatory
      disease, modulation of the immune system may be a promising approach. Previously,
      it was suggested that antibodies may confer protective effects on the development
      of atherosclerosis. In this study, we hypothesised that passive immunization with
      anti-oxLDL IgM antibodies specific for hypochlorite (HOCl) may be athero
      protective in mice. METHODS AND RESULTS: Monoclonal mouse IgM antibodies were
      produced and the antibody with specificity for hypochlorite-oxLDL (HOCl-oxLDL)
      (Moab A7S8) was selected. VH sequence determination revealed that Moab A7S8 is a
      natural IgM antibody. Atherosclerosis in LDLr(-/-) mice was induced by a
      perivascular collar placement around the right carotid artery in combination with
      feeding a high-fat diet. Subsequently, the mice were treated every six days with
      500 ug Moab A7S8, non-relevant IgM or with PBS and the carotid arteries and
      aortic roots were studied for atherosclerosis. Passive immunization with this
      Moab A7S8 resulted in a significant reduced plaque volume formation in LDLr(-/-)
      mice when compared with PBS treatment (P = 0.002 and P = 0.035). Cholesterol
      levels decreased by 20% when mice were treated with Moab A7S8 compared to PBS.
      Furthermore, anti-oxLDL specific IgM and IgG antibody production increased
      significantly in the Moab A7S8 treated mice in comparison with PBS treated mice.
      CONCLUSION: Our data show that passive immunization with a natural IgM antibody,
      directed to HOCl-oxLDL, can reduce atherosclerotic plaque development. We
      postulate that specific antibody therapy may be developed for use in human
      cardiovascular diseases.

PMID- 23874491
TI  - Visual interactions conform to pattern decorrelation in multiple cortical areas.
AB  - Neural responses to visual stimuli are strongest in the classical receptive
      field, but they are also modulated by stimuli in a much wider region. In the
      primary visual cortex, physiological data and models suggest that such contextual
      modulation is mediated by recurrent interactions between cortical areas. Outside
      the primary visual cortex, imaging data has shown qualitatively similar
      interactions. However, whether the mechanisms underlying these effects are
      similar in different areas has remained unclear. Here, we found that the blood
      oxygenation level dependent (BOLD) signal spreads over considerable cortical
      distances in the primary visual cortex, further than the classical receptive
      field. This indicates that the synaptic activity induced by a given stimulus
      occurs in a surprisingly extensive network. Correspondingly, we found suppressive
      and facilitative interactions far from the maximum retinotopic response. Next, we
      characterized the relationship between contextual modulation and correlation
      between two spatial activation patterns. Regardless of the functional area or
      retinotopic eccentricity, higher correlation between the center and surround
      response patterns was associated with stronger suppressive interaction. In
      individual voxels, suppressive interaction was predominant when the center and
      surround stimuli produced BOLD signals with the same sign. Facilitative
      interaction dominated in the voxels with opposite BOLD signal signs. Our data was
      in unison with recently published cortical decorrelation model, and was validated
      against alternative models, separately in different eccentricities and functional
      areas. Our study provides evidence that spatial interactions among neural
      populations involve decorrelation of macroscopic neural activation patterns, and
      suggests that the basic design of the cerebral cortex houses a robust
      decorrelation mechanism for afferent synaptic input. 

PMID- 23874492
TI  - Moderate alcohol use and cardiovascular disease from Mendelian randomization.
AB  - BACKGROUND: Observational studies show moderate alcohol use negatively associated
      with ischemic heart disease (IHD) and cardiovascular disease (CVD). However,
      healthier attributes among moderate users compared to never users may confound
      the apparent association. A potentially less biased way to examine the
      association is Mendelian randomization, using alcohol metabolizing genes which
      influence alcohol use. METHODS: We used instrumental variable analysis with
      aldehyde dehydrogenase 2 (ALDH2) genotypes (AA/GA/GG) as instrumental variables
      for alcohol use to examine the association of alcohol use (10 g ethanol/day) with
      CVD risk factors (blood pressure, lipids and glucose) and morbidity (self
      reported IHD and CVD) among men in the Guangzhou Biobank Cohort Study. RESULTS:
      ALDH2 genotypes were a credible instrument for alcohol use (F-statistic 74.6).
      Alcohol was positively associated with HDL-cholesterol (0.05 mmol/L per alcohol
      unit, 95% confidence interval (CI) 0.02 to 0.08) and diastolic blood pressure
      (1.15 mmHg, 95% CI 0.23 to 2.07) but not with systolic blood pressure (1.00 mmHg,
      95% CI -0.74 to 2.74), LDL-cholesterol (0.03 mmol/L, 95% CI -0.03 to 0.08), log
      transformed triglycerides (0.03 mmol/L, 95% CI -0.01 to 0.08) or log transformed
      fasting glucose (0.01 mmol/L, 95% CI -0.006 to 0.03), self-reported CVD (odds
      ratio (OR) 0.98, 95% CI 0.76 to 1.27) or self-reported IHD (OR 1.10, 95% CI 0.83
      to 1.45). CONCLUSION: Low to moderate alcohol use among men had the expected
      effects on most CVD risk factors but not fasting glucose. Larger studies are
      needed to confirm the null associations with IHD, CVD and fasting glucose.

PMID- 23874493
TI  - Microbial translocation contribute to febrile episodes in adults with
      chemotherapy-induced neutropenia.
AB  - In this study we sought to determine the contribution of microbial translocation
      to febrile episodes with no attributable microbiological cause (Fever of Unknown
      Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations
      were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct
      measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA
      was selected as an indicator of the early host response to endotoxins. Endotoxin
      concentrations in this cohort were generally elevated but did not differ with the
      presentation of fever. Further stratification of the febrile episodes based on
      the microbiological findings revealed significantly (p = 0.0077) elevated
      endotoxin concentrations in FUO episodes compared with episodes with documented
      bacterial and viral findings. sCD14 concentrations were however, elevated in
      febrile episodes (p = 0.0066) and no association was observed between sCD14
      concentration and microbiological findings. However, FUO episodes and episodes
      with Gram-negative bacteraemia were associated with higher median sCD14
      concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In
      conclusion, our findings suggest that in the absence of microbiological findings,
      microbial translocation could contribute to febrile episodes in an adult
      neutropaenic cohort. We further observed an association between prophylactic
      antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).

PMID- 23874494
TI  - Identification and validation of reference genes for gene expression analysis
      using quantitative PCR in Spodoptera litura (Lepidoptera: Noctuidae).
AB  - Reverse transcription quantitative polymerase chain reaction (qRT-PCR) has
      rapidly become the most sensitive and accurate method for the quantification of
      gene expression. To facilitate gene expression studies and obtain more accurate
      qRT-PCR data, normalization relative to stable housekeeping genes is required.
      These housekeeping genes need to show stable expression under the given
      experimental conditions for the qRT-PCR results to be accurate. Unfortunately,
      there are no studies on the stability of housekeeping genes used in Spodoptera
      litura. In this study, eight candidate reference genes, elongation factor 1 alpha
      (EF1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ribosomal protein L10
      (RPL10), ribosomal protein S3 (RPS3), beta actin (ACTB), beta FTZ-F1 (FTZF1),
      ubiquinol-cytochrome c reductase (UCCR), and arginine kinase (AK), were evaluated
      for their suitability as normalization genes under different experimental
      conditions using the statistical software programs, BestKeeper, geNorm and
      Normfinder, and the comparative DeltaCt method. We determined the expression
      levels of the candidate reference genes for three biotic factors (developmental
      stage, tissue and population), and four abiotic treatments (temperature,
      insecticide, food and starvation). The results indicated that the best sets of
      candidates as reference genes were as follows: GAPDH and UCCR for developmental
      stages; RPL10, AK and EF1 for different tissues; RPL10 and EF1 for different
      populations in China; GAPDH and EF1 for temperature-stressed larvae; AK and ACTB
      for larvae treated with different insecticides; RPL10, GAPDH and UCCR for larvae
      fed different diets; RPS3 and ACTB for starved larvae. We believe that these
      results make an important contribution to gene analysis studies in S. litura and
      form the basis of further research on stable reference genes in S. litura and
      other organisms. 

PMID- 23874495
TI  - From START to FINISH: the influence of osmotic stress on the cell cycle.
AB  - The cell cycle is a sequence of biochemical events that are controlled by complex
      but robust molecular machinery. This enables cells to achieve accurate self
      reproduction under a broad range of different conditions. Environmental changes
      are transmitted by molecular signalling networks, which coordinate their action
      with the cell cycle. The cell cycle process and its responses to environmental
      stresses arise from intertwined nonlinear interactions among large numbers of
      simpler components. Yet, understanding of how these pieces fit together into a
      coherent whole requires a systems biology approach. Here, we present a novel
      mathematical model that describes the influence of osmotic stress on the entire
      cell cycle of S. cerevisiae for the first time. Our model incorporates all
      recently known and several proposed interactions between the osmotic stress
      response pathway and the cell cycle. This model unveils the mechanisms that
      emerge as a consequence of the interaction between the cell cycle and stress
      response networks. Furthermore, it characterises the role of individual
      components. Moreover, it predicts different phenotypical responses for cells
      depending on the phase of cells at the onset of the stress. The key predictions
      of the model are: (i) exposure of cells to osmotic stress during the late S and
      the early G2/M phase can induce DNA re-replication before cell division occurs,
      (ii) cells stressed at the late G2/M phase display accelerated exit from mitosis
      and arrest in the next cell cycle, (iii) osmotic stress delays the G1-to-S and G2
      to-M transitions in a dose dependent manner, whereas it accelerates the M-to-G1
      transition independently of the stress dose and (iv) the Hog MAPK network
      compensates the role of the MEN network during cell division of MEN mutant cells.
      These model predictions are supported by independent experiments in S. cerevisiae
      and, moreover, have recently been observed in other eukaryotes. 

PMID- 23874496
TI  - Association of mitochondrial genetic variation with carotid atherosclerosis.
AB  - In human pathology, several diseases are associated with somatic mutations in the
      mitochondrial genome (mtDNA). Even though mitochondrial dysfunction leads to
      increased oxidative stress, the role of mitochondrial mutations in
      atherosclerosis has not received much attention so far. In this study we analyzed
      the association of mitochondrial genetic variation with the severity of carotid
      atherosclerosis, as assessed by carotid intima-media thickness (cIMT) and the
      presence of coronary heart disease (CHD) in 190 subjects from Moscow, Russia, a
      population with high CHD occurrence. cIMT was measured by high-resolution B-mode
      ultrasonography and mtDNA heteroplasmies by a pyrosequencing-based method. We
      found that heteroplasmies for several mutations in the mtDNA in leukocytes,
      including C3256T, T3336C, G12315A, G13513A, G14459A, G14846A, and G15059A
      mutations, were significantly (p<0.001) associated with both the severity of
      carotid atherosclerosis and the presence of CHD. These findings indicate that
      somatic mitochondrial mutations have a role in the development of
      atherosclerosis. 

PMID- 23874497
TI  - Bayesian mixture models for assessment of gene differential behaviour and
      prediction of pCR through the integration of copy number and gene expression
      data.
AB  - We consider modeling jointly microarray RNA expression and DNA copy number data.
      We propose Bayesian mixture models that define latent Gaussian probit scores for
      the DNA and RNA, and integrate between the two platforms via a regression of the
      RNA probit scores on the DNA probit scores. Such a regression conveniently allows
      us to include additional sample specific covariates such as biological conditions
      and clinical outcomes. The two developed methods are aimed respectively to make
      inference on differential behaviour of genes in patients showing different
      subtypes of breast cancer and to predict the pathological complete response (pCR)
      of patients borrowing strength across the genomic platforms. Posterior inference
      is carried out via MCMC simulations. We demonstrate the proposed methodology
      using a published data set consisting of 121 breast cancer patients. 

PMID- 23874498
TI  - QuateXelero: an accelerated exact network motif detection algorithm.
AB  - Finding motifs in biological, social, technological, and other types of networks
      has become a widespread method to gain more knowledge about these networks'
      structure and function. However, this task is very computationally demanding,
      because it is highly associated with the graph isomorphism which is an NP problem
      (not known to belong to P or NP-complete subsets yet). Accordingly, this research
      is endeavoring to decrease the need to call NAUTY isomorphism detection method,
      which is the most time-consuming step in many existing algorithms. The work
      provides an extremely fast motif detection algorithm called QuateXelero, which
      has a Quaternary Tree data structure in the heart. The proposed algorithm is
      based on the well-known ESU (FANMOD) motif detection algorithm. The results of
      experiments on some standard model networks approve the overal superiority of the
      proposed algorithm, namely QuateXelero, compared with two of the fastest existing
      algorithms, G-Tries and Kavosh. QuateXelero is especially fastest in constructing
      the central data structure of the algorithm from scratch based on the input
      network. 

PMID- 23874499
TI  - Evolution of the plasma and tissue kallikreins, and their alternative splicing
      isoforms.
AB  - Kallikreins are secreted serine proteases with important roles in human
      physiology. Human plasma kallikrein, encoded by the KLKB1 gene on locus 4q34-35,
      functions in the blood coagulation pathway, and in regulating blood pressure. The
      human tissue kallikrein and kallikrein-related peptidases (KLKs) have diverse
      expression patterns and physiological roles, including cancer-related processes
      such as cell growth regulation, angiogenesis, invasion, and metastasis. Prostate
      specific antigen (PSA), the product of the KLK3 gene, is the most widely used
      biomarker in clinical practice today. A total of 15 KLKs are encoded by the
      largest contiguous cluster of protease genes in the human genome (19q13.3-13.4),
      which makes them ideal for evolutionary analysis of gene duplication events.
      Previous studies on the evolution of KLKs have traced mammalian homologs as well
      as a probable early origin of the family in aves, amphibia and reptilia. The aim
      of this study was to address the evolutionary and functional relationships
      between tissue KLKs and plasma kallikrein, and to examine the evolution of
      alternative splicing isoforms. Sequences of plasma and tissue kallikreins and
      their alternative transcripts were collected from the NCBI and Ensembl databases,
      and comprehensive phylogenetic analysis was performed by Bayesian as well as
      maximum likelihood methods. Plasma and tissue kallikreins exhibit high sequence
      similarity in the trypsin domain (>50%). Phylogenetic analysis indicates an early
      divergence of KLKB1, which groups closely with plasminogen, chymotrypsin, and
      complement factor D (CFD), in a monophyletic group distinct from trypsin and the
      tissue KLKs. Reconstruction of the earliest events leading to the diversification
      of the tissue KLKs is not well resolved, indicating rapid expansion in mammals.
      Alternative transcripts of each KLK gene show species-specific divergence, while
      examination of sequence conservation indicates that many annotated human KLK
      isoforms are missing the catalytic triad that is crucial for protease activity. 

PMID- 23874500
TI  - DNA homologous recombination factor SFR1 physically and functionally interacts
      with estrogen receptor alpha.
AB  - Estrogen receptor alpha (ERalpha), a ligand-dependent transcription factor,
      mediates the expression of its target genes by interacting with corepressors and
      coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor
      cofactors have been identified, which orchestrate target gene transcription.
      Aberrant activity of ER or its accessory proteins results in a number of diseases
      including breast cancer. Here we identified SFR1, a protein involved in DNA
      homologous recombination, as a novel binding partner of ERalpha. Initially
      isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERalpha was
      confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co
      localized with ERalpha in the nucleus, potentiated ER's ligand-dependent and
      ligand-independent transcriptional activity, and occupied the ER binding sites of
      its target gene promoters. Knockdown of SFR1 diminished ER's transcriptional
      activity. Manipulating SFR1 expression by knockdown and overexpression revealed a
      role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1
      differs from SRC1 by the lack of an intrinsic activation function. Taken
      together, we propose that SFR1 is a novel transcriptional modulator for ERalpha
      and a potential target in breast cancer therapy. 

PMID- 23874501
TI  - Inhibition of dual/mixed tropic HIV-1 isolates by CCR5-inhibitors in primary
      lymphocytes and macrophages.
AB  - BACKGROUND: Dual/mixed-tropic HIV-1 strains are predominant in a significant
      proportion of patients, though little information is available regarding their
      replication-capacity and susceptibility against CCR5-antagonists in-vitro. The
      aim of the study was to analyze the replication-capacity and susceptibility to
      maraviroc of HIV-1 clinical isolates with different tropism characteristics in
      primary monocyte-derived-macrophages (MDM), peripheral-blood-mononuclear-cells
      (PBMC), and CD4(+) T-lymphocytes. METHODS: Twenty-three HIV-1 isolates were
      phenotipically and genotipically characterized as R5, X4 or dual (discriminated
      as R5(+)/X4, R5/X4, R5/X4(+)). Phenotypic-tropism was evaluated by multiple
      cycles-assay on U87MG-CD4(+)-CCR5(+)-/CXCR4(+)-expressing cells. Genotypic
      tropism prediction was obtained using Geno2Pheno-algorithm (false-positive-rate
      [FPR] = 10%). Replication-capacity and susceptibility to maraviroc were
      investigated in human-primary MDM, PBMC and CD4(+) T-cells. AMD3100 was used as
      CXCR4-inhibitor. Infectivity of R5/Dual/X4-viruses in presence/absence of
      maraviroc was assessed also by total HIV-DNA, quantified by real-time polymerase
      chain-reaction. RESULTS: Among 23 HIV-1 clinical isolates, phenotypic-tropism
      assay distinguished 4, 17 and 2 viruses with R5-tropic, dual/mixed-, and X4
      tropic characteristics, respectively. Overall, viruses defined as R5(+)/X4-tropic
      were found with the highest prevalence (10/23, 43.5%). The majority of isolates
      efficiently replicated in both PBMC and CD4(+) T-cells, regardless of their
      tropism, while MDM mainly sustained replication of R5- or R5(+)/X4-tropic
      isolates; strong correlation between viral-replication and genotypic-FPR-values
      was observed in MDM (rho = 0.710;p-value = 1.4e-4). In all primary cells,
      maraviroc inhibited viral-replication of isolates not only with pure R5- but also
      with dual/mixed tropism (mainly R5(+)/X4 and, to a lesser extent R5/X4 and
      R5/X4(+)). Finally, no main differences by comparing the total HIV-DNA with the
      p24-production in presence/absence of maraviroc were found. CONCLUSIONS:
      Maraviroc is effective in-vitro against viruses with dual-characteristics in both
      MDM and lymphocytes, despite the potential X4-mediated escape. This suggests that
      the concept of HIV-entry through one of the two coreceptors "separately" may
      require revision, and that the use of CCR5-antagonists in patients with
      dual/mixed-tropic viruses may be a therapeutic-option that deserves further
      investigations in different clinical settings.

PMID- 23874502
TI  - A novel, non-canonical splice variant of the Ikaros gene is aberrantly expressed
      in B-cell lymphoproliferative disorders.
AB  - The Ikaros gene encodes a Kruppel-like zinc-finger transcription factor involved
      in hematopoiesis regulation. Ikaros has been established as one of the most
      clinically relevant tumor suppressors in several hematological malignancies. In
      fact, expression of dominant negative Ikaros isoforms is associated with adult B
      cell acute lymphoblastic leukemia, myelodysplastic syndrome, acute myeloid
      leukemia and adult and juvenile chronic myeloid leukemia. Here, we report the
      isolation of a novel, non-canonical Ikaros splice variant, called Ikaros 11
      (Ik11). Ik11 is structurally related to known dominant negative Ikaros isoforms,
      due to the lack of a functional DNA-binding domain. Interestingly, Ik11 is the
      first Ikaros splice variant missing the transcriptional activation domain.
      Indeed, we demonstrated that Ik11 works as a dominant negative protein, being
      able to dimerize with Ikaros DNA-binding isoforms and inhibit their functions, at
      least in part by retaining them in the cytoplasm. Notably, we demonstrated that
      Ik11 is the first dominant negative Ikaros isoform to be aberrantly expressed in
      B-cell lymphoproliferative disorders, such as chronic lymphocytic leukemia.
      Aberrant expression of Ik11 interferes with both proliferation and apoptotic
      pathways, providing a mechanism for Ik11 involvement in tumor pathogenesis. Thus,
      Ik11 could represent a novel marker for B-cell lymphoproliferative disorders. 

PMID- 23874503
TI  - How much variation can one ant species hold? Species delimitation in the
      Crematogaster kelleri-group in Madagascar.
AB  - We investigated the species-level taxonomy of the Malagasy Crematogaster
      (Crematogaster) kelleri-group and an additional more distantly related species of
      the same subgenus. Morphological data from worker, queen and male ants, as well
      as genetic data from three nuclear genes (long wavelength rhodopsin, arginine
      kinase and carbomoylphosphate synthase) and one mitochondrial marker (cytochrome
      oxidase I) led to the recognition of six species. Within the C. kelleri-group,
      three new species are described: C. hazolava Blaimer sp. n., C. hafahafa Blaimer
      sp. n. and C. tavaratra Blaimer sp. n. The previously described taxa C. kelleri
      Forel and C. madagascariensis Andre are validated by our analysis. Conversely,
      our data suggests synonymy of C. adrepens Forel (with C. kelleri) and C. gibba
      Emery (with C. madagascariensis). A more distantly related and phylogenetically
      isolated species, C. tsisitsilo Blaimer sp. n., is further described. We report
      high levels of morphological and molecular variation in C. kelleri and illustrate
      that this variation can be explained partly by geography. Species descriptions,
      images, distribution maps and identification keys based on worker ants, as well
      as on queen and male ants where available, are presented for all six species. Our
      work highlights the elevated species richness of Crematogaster ants throughout
      Madagascar's humid forests, especially in the far northern tip of the island, and
      the need to use multiple data sources to ensure clear demarcation of this
      diversity. 

PMID- 23874504
TI  - Analysis of the behaviours mediating barnacle cyprid reversible adhesion.
AB  - When exploring immersed surfaces the cypris larvae of barnacles employ a
      tenacious and rapidly reversible adhesion mechanism to facilitate their
      characteristic 'walking' behaviour. Although of direct relevance to the fields of
      marine biofouling and bio-inspired adhesive development, the mechanism of
      temporary adhesion in cyprids remains poorly understood. Cyprids secrete deposits
      of a proteinaceous substance during surface attachment and these are often
      visible as 'footprints' on previously explored surfaces. The attachment
      structures, the antennular discs, of cyprids also present a complex morphology
      reminiscent of both the hairy appendages used by some terrestrial invertebrates
      for temporary adhesion and a classic 'suction cup'. Despite the numerous
      analytical approaches so-far employed, it has not been possible to resolve
      conclusively the respective contributions of viscoelastic adhesion via the
      proteinaceous 'temporary adhesive', 'dry' adhesion via the cuticular villi
      present on the disc and the behavioural contribution by the organism. In this
      study, high-speed photography was used for the first time to capture the
      behaviour of cyprids at the instant of temporary attachment and detachment.
      Attachment is facilitated by a constantly sticky disc surface - presumably due to
      the presence of the proteinaceous temporary adhesive. The tenacity of the
      resulting bond, however, is mediated behaviourally. For weak attachment the disc
      is constantly moved on the surface, whereas for a strong attachment the disc is
      spread out on the surface. Voluntary detachment is by force, requiring twisting
      or peeling of the bond - seemingly without any more subtle detachment behaviours.
      Micro-bubbles were observed at the adhesive interface as the cyprid detached,
      possibly an adaptation for energy dissipation. These observations will allow
      future work to focus more specifically on the cyprid temporary adhesive proteins,
      which appear to be fundamental to adhesion, inherently sticky and exquisitely
      adapted for reversible adhesion underwater. 

PMID- 23874505
TI  - External suction versus water seal after selective pulmonary resection for lung
      neoplasm: a systematic review.
AB  - OBJECTIVE: To evaluate whether external suction is more advantageous than water
      seal in patients undergoing selective pulmonary resection (SPR) for lung
      neoplasm. SUMMARY OF BACKGROUND DATA: Whether external suction should be
      routinely applied in postoperative chest drainage is still unclear, particularly
      for lung neoplasm patients. To most surgeons, the decision is based on their
      clinical experience. METHODS: Randomized control trials were selected. The
      participants were patients undergoing SPR with lung neoplasm. Lung volume
      reduction surgery and pneumothorax were excluded. Suction versus non-suction for
      the intervention. The primary outcome was the incidence of persistent air leak
      (PAL). The definition of PAL was air leak for more than 3-7 days. The secondary
      outcomes included air leak duration, time of drainage, postoperative hospital
      stay and the incidence of postoperative pneumothorax. Studies were identified
      from literature collections through screening. Bias was analyzed and meta
      analysis was used. RESULTS: From the 1824 potentially relevant trials, 6
      randomized control trials involving 676 patients were included. There was no
      difference between external suction and water seal in decreasing the incidence of
      PAL [95% confidence interval (CI) 0.81-2.16; z = 1.10; P = 0.27]. Regarding
      secondary outcomes, there were no differences in time of drainage (95% CI-0.36
      1.56, P = 0.22), postoperative hospital stay (95% CI -.31-.54, P = 0.87) or
      incidence of postoperative pneumothorax (95% CI 0.18-.02, P = 0.05) between
      external suction and water seal. CONCLUSIONS: For participants, no differences
      are identified in terms of PAL incidence, drainage time, length of postoperative
      hospital stay or incidence of postoperative pneumothorax between external suction
      and water seal. The bias analysis should be emphasized. To the limitations of the
      bias and methodological differences among the included studies, we have no
      recommendation on whether external suction should be routinely applied after lung
      neoplasm SPR. More high-quality randomized controlled trials are needed.
      SYSTEMATIC REVIEW REGISTRATION: None.

PMID- 23874506
TI  - CpG methylation changes within the IL2RA promoter in type 1 diabetes of childhood
      onset.
AB  - None of the polymorphic variants of the IL2RA gene found associated with Type 1
      Diabetes (T1D) was shown to have a functional effect. To test if the epigenetic
      variation could play a role at this locus, we studied the methylation of 6 CpGs
      located within the proximal promoter of IL2RA gene in 252 T1D patients compared
      with 286 age-matched controls. We found that DNA methylation at CpGs -373 and 
      456 was slightly but significantly higher in patients than in controls (40.4 +/-
      4.6 vs 38.3 +/- 5.4, p=1.4E4; 91.4 +/- 2.8 vs 89.5 +/- 5.3, p=1.8E-6), while
      other CpG showed a strictly comparable methylation. Among 106 single nucleotide
      polymorphisms (SNPs) located in the neighboring 180 kb region, we found that 28
      SNPs were associated with DNA methylation at CpG -373. Sixteen of these SNPs were
      known to be associated with T1D. Our findings suggest that the effect of IL2RA
      risk alleles on T1D may be partially mediated through epigenetic changes.

PMID- 23874509
TI  - Development of a rapid and efficient method for non-lethal DNA sampling and
      genotyping in scallops.
AB  - Non-lethal DNA sampling has long appealed to researchers studying population and
      conservation genetics, as it does not necessitate removing individuals
      permanently from their natural environment or destroying valuable samples.
      However, such an approach has not yet been well established in bivalves. In this
      study, we demonstrate that the gill represents a good source of tissue for non
      lethal sampling in scallops. Removal of a few gill filaments caused no noticeable
      behavioral abnormalities or increased mortality rates in Zhikong scallop (Chlamys
      farreri) during a three-month period of observation. To facilitate rapid gill
      based DNA extraction, six methods (MA-MF) were designed and evaluated, each
      requiring less than one hour of processing time. The optimal method was
      identified as MF, in terms of maintaining DNA integrity and genotyping accuracy.
      Further optimization of MF method by orthogonal experimental design suggested
      that the utilization of gills could be limited to 2 mg of sample, which is
      sufficient for performing up to 20,000 PCR reactions. We also demonstrate the
      excellent cross-species utility of MF in two additional scallop species, Yesso
      scallop (Patinopecten yessoensis) and bay scallop (Argopecten irradians). Taken
      together, our study provides a rapid and efficient approach for applying non
      lethal DNA sampling in bivalve species, which would serve as a valuable tool for
      maintaining bivalve populations and conservation genetics, as well as in breeding
      studies. 

PMID- 23874507
TI  - Characterization of chromosome stability in diploid, polyploid and hybrid yeast
      cells.
AB  - Chromosome instability is a key component of cancer progression and many
      heritable diseases. Understanding why some chromosomes are more unstable than
      others could provide insight into understanding genome integrity. Here we
      systematically investigate the spontaneous chromosome loss for all sixteen
      chromosomes in Saccharomyces cerevisiae in order to elucidate the mechanisms
      underlying chromosome instability. We observed that the stability of different
      chromosomes varied more than 100-fold. Consistent with previous studies on
      artificial chromosomes, chromosome loss frequency was negatively correlated to
      chromosome length in S. cerevisiae diploids, triploids and S. cerevisiae-S.
      bayanus hybrids. Chromosome III, an equivalent of sex chromosomes in budding
      yeast, was found to be the most unstable chromosome among all cases examined.
      Moreover, similar instability was observed in chromosome III of S. bayanus, a
      species that diverged from S. cerevisiae about 20 million years ago, suggesting
      that the instability is caused by a conserved mechanism. Chromosome III was found
      to have a highly relaxed spindle checkpoint response in the genome. Using a
      plasmid stability assay, we found that differences in the centromeric sequence
      may explain certain aspects of chromosome instability. Our results reveal that
      even under normal conditions, individual chromosomes in a genome are subject to
      different levels of pressure in chromosome loss (or gain). 

PMID- 23874508
TI  - Best practices and joint calling of the HumanExome BeadChip: the CHARGE
      Consortium.
AB  - Genotyping arrays are a cost effective approach when typing previously-identified
      genetic polymorphisms in large numbers of samples. One limitation of genotyping
      arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the
      difficulty that automated clustering algorithms have to accurately detect and
      assign genotype calls. Combining intensity data from large numbers of samples may
      increase the ability to accurately call the genotypes of rare variants.
      Approximately 62,000 ethnically diverse samples from eleven Cohorts for Heart and
      Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts were genotyped
      with the Illumina HumanExome BeadChip across seven genotyping centers. The raw
      data files for the samples were assembled into a single project for joint
      calling. To assess the quality of the joint calling, concordance of genotypes in
      a subset of individuals having both exome chip and exome sequence data was
      analyzed. After exclusion of low performing SNPs on the exome chip and non
      overlap of SNPs derived from sequence data, genotypes of 185,119 variants (11,356
      were monomorphic) were compared in 530 individuals that had whole exome sequence
      data. A total of 98,113,070 pairs of genotypes were tested and 99.77% were
      concordant, 0.14% had missing data, and 0.09% were discordant. We report that
      joint calling allows the ability to accurately genotype rare variation using
      array technology when large sample sizes are available and best practices are
      followed. The cluster file from this experiment is available at
      www.chargeconsortium.com/main/exomechip. 

PMID- 23874510
TI  - Effects of white matter injury on resting state fMRI measures in prematurely born
      infants.
AB  - The cerebral white matter is vulnerable to injury in very preterm infants (born
      prior to 30 weeks gestation), resulting in a spectrum of lesions. These range
      from severe forms, including cystic periventricular leukomalacia and
      periventricular hemorrhagic infarction, to minor focal punctate lesions. Moderate
      to severe white matter injury in preterm infants has been shown to predict later
      neurodevelopmental disability, although outcomes can vary widely in infants with
      qualitatively comparable lesions. Resting state functional connectivity magnetic
      resonance imaging has been increasingly utilized in neurodevelopmental
      investigations and may provide complementary information regarding the impact of
      white matter injury on the developing brain. We performed resting state
      functional connectivity magnetic resonance imaging at term equivalent
      postmenstrual age in fourteen preterm infants with moderate to severe white
      matter injury secondary to periventricular hemorrhagic infarction. In these
      subjects, resting state networks were identifiable throughout the brain. Patterns
      of aberrant functional connectivity were observed and depended upon injury
      severity. Comparisons were performed against data obtained from prematurely-born
      infants with mild white matter injury and healthy, term-born infants and
      demonstrated group differences. These results reveal structural-functional
      correlates of preterm white matter injury and carry implications for future
      investigations of neurodevelopmental disability. 

PMID- 23874512
TI  - Seasonal variations in notification of active tuberculosis cases in China, 2005
      2012.
AB  - BACKGROUND: Although seasonal variation in tuberculosis (TB) incidence has been
      described in many countries, it remains unknown in China. METHODS: A time series
      decomposition analysis (X-12-ARIMA) was performed to examine the seasonal
      variation in active TB cases nationwide from 2005 through 2012 in China. Seasonal
      amplitude was calculated for the evaluation of TB seasonal variation. RESULTS: A
      total of 7.78 million active TB cases were reported over a period of 8 years. A
      spring peak (April) was observed with seasonal amplitude of 46.3%, compared with
      the winter trough (February). Most cases in provinces with subtropical and
      tropical monsoon climate showed lower amplitudes than those in temperate
      continental, plateau and mountain climate regions. The magnitude of seasonality
      varied inversely with annual average temperature, r (95% CI) = -0.71 (-0.79, 
      0.61). The seasonal amplitudes were 56.7, 60.5, 40.6, 46.4 and 50.9% for patients
      aged <=14, 15-24, 25-44, 45-64, and >=65 years, respectively. Students
      demonstrated greater seasonal amplitude than peasants, migrant workers and
      workers (115.3% vs. 43.5, 41.6 and 48.1%). Patients with pulmonary TB had lower
      amplitude compared to patients with pleural and other extra-pulmonary TB (EPTB)
      (45.9% vs. 52.0 and 56.3%). Relapse cases with sputum smear positive TB (SS+ TB)
      had significantly higher seasonal amplitude compared to new cases with sputum
      smear positive TB (52.2% vs. 41.6%). CONCLUSIONS: TB is a seasonal disease in
      China. The peak and trough of TB transmission actually are in winter and in
      autumn respectively after factors of delay are removed. Higher amplitudes of TB
      seasonality are more likely to happen in temperate continental, plateau and
      mountain climate regions and regions with lower annual average temperature, and
      young person, students, patients with EPTB and relapse cases with SS+ TB are more
      likely to be affected by TB seasonality.

PMID- 23874511
TI  - Enzymatic formulation capable of degrading scrapie prion under mild digestion
      conditions.
AB  - The prion agent is notoriously resistant to common proteases and conventional
      sterilisation procedures. The current methods known to destroy prion infectivity
      such as incineration, alkaline and thermal hydrolysis are harsh, destructive,
      environmentally polluting and potentially hazardous, thus limit their
      applications for decontamination of delicate medical and laboratory devices,
      remediation of prion contaminated environment and for processing animal by
      products including specified risk materials and carcases. Therefore, an
      environmentally friendly, non-destructive enzymatic degradation approach is
      highly desirable. A feather-degrading Bacillus licheniformis N22 keratinase has
      been isolated which degraded scrapie prion to undetectable level of PrP(Sc)
      signals as determined by Western Blot analysis. Prion infectivity was verified by
      ex vivo cell-based assay. An enzymatic formulation combining N22 keratinase and
      biosurfactant derived from Pseudomonas aeruginosa degraded PrP(Sc) at 65  degrees
      C in 10 min to undetectable level -. A time-course degradation analysis carried
      out at 50  degrees C over 2 h revealed the progressive attenuation of PrP(Sc)
      intensity. Test of residual infectivity by standard cell culture assay confirmed
      that the enzymatic formulation reduced PrP(Sc) infectivity to undetectable levels
      as compared to cells challenged with untreated standard scrapie sheep prion
      (SSBP/1) (p-value = 0.008 at 95% confidence interval). This novel enzymatic
      formulation has significant potential application for prion decontamination in
      various environmentally friendly systems under mild treatment conditions.

PMID- 23874513
TI  - Absence of mutations in exon 6 of the TARDBP gene in 207 Chinese patients with
      sporadic amyotrohic lateral sclerosis.
AB  - Mutations in the TARDBP gene, which encodes the Tar DNA binding protein, have
      been shown to causes of both familial amyotrophic lateral sclerosis (FALS) and
      sporadic ALS (SALS). Recently, several novel TARDBP exon 6 mutants have been
      reported in patients with ALS in Europe and America but not in Asia. To further
      examine the spectrum and frequency of TARDBP exon 6 mutations, we investigated
      their frequency in ethnic Chinese patients with sporadic ALS. TARDBP exon 6 was
      screened by direct sequencing in 207 non-SOD1 SALS patients and 230 unrelated
      healthy controls but no mutations were identified. Our data indicate that exon 6
      mutations in TARDBP are not a common cause of SALS in Han Chinese population from
      Southern Mainland China. 

PMID- 23874514
TI  - HLA alleles influence the clinical signature of amoxicillin-clavulanate
      hepatotoxicity.
AB  - BACKGROUND AND AIM: The genotype-phenotype interaction in drug-induced liver
      injury (DILI) is a subject of growing interest. Previous studies have linked
      amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA
      alleles. In this study we aimed to examine potential associations between HLA
      class I and II alleles and AC DILI with regards to phenotypic characteristics,
      severity and time to onset in Spanish AC hepatotoxicity cases. METHODS: High
      resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC
      DILI cases and 885 controls. RESULTS: The distributions of class I alleles A*3002
      (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more
      frequently found in hepatocellular injury cases compared to controls. In
      addition, the presence of the class II allele combination DRB1*1501-DQB1*0602
      (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed
      cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65
      years, P = 0.019) and were more frequently hospitalized than the DRB1*1501
      DQB1*0602 carriers. No additional alleles outside those associated with liver
      injury patterns were found to affect potential severity as measured by Hy's Law
      criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and
      DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases
      with delayed onset compared to those corresponding to patients without delayed
      onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR
      0.07). CONCLUSIONS: HLA class I and II alleles influence the AC DILI signature
      with regards to phenotypic expression, latency presentation and severity in
      Spanish patients.

PMID- 23874515
TI  - Shotgun redox proteomics: identification and quantitation of carbonylated
      proteins in the UVB-resistant marine bacterium, Photobacterium angustum S14.
AB  - UVB oxidizes proteins through the generation of reactive oxygen species. One
      consequence of UVB irradiation is carbonylation, the irreversible formation of a
      carbonyl group on proline, lysine, arginine or threonine residues. In this study,
      redox proteomics was performed to identify carbonylated proteins in the UVB
      resistant marine bacterium Photobacterium angustum. Mass-spectrometry was
      performed with either biotin-labeled or dinitrophenylhydrazide (DNPH) derivatized
      proteins. The DNPH redox proteomics method enabled the identification of 62
      carbonylated proteins (5% of 1221 identified proteins) in cells exposed to UVB or
      darkness. Eleven carbonylated proteins were quantified and the UVB/dark abundance
      ratio was determined at both the protein and peptide levels. As a result we
      determined which functional classes of proteins were carbonylated, which residues
      were preferentially modified, and what the implications of the carbonylation were
      for protein function. As the first large scale, shotgun redox proteomics analysis
      examining carbonylation to be performed on bacteria, our study provides a new
      level of understanding about the effects of UVB on cellular proteins, and
      provides a methodology for advancing studies in other biological systems. 

PMID- 23874516
TI  - Auditory cortical areas activated by slow frequency-modulated sounds in mice.
AB  - Species-specific vocalizations in mice have frequency-modulated (FM) components
      slower than the lower limit of FM direction selectivity in the core region of the
      mouse auditory cortex. To identify cortical areas selective to slow frequency
      modulation, we investigated tonal responses in the mouse auditory cortex using
      transcranial flavoprotein fluorescence imaging. For differentiating responses to
      frequency modulation from those to stimuli at constant frequencies, we focused on
      transient fluorescence changes after direction reversal of temporally repeated
      and superimposed FM sweeps. We found that the ultrasonic field (UF) in the belt
      cortical region selectively responded to the direction reversal. The
      dorsoposterior field (DP) also responded weakly to the reversal. Regarding the
      responses in UF, no apparent tonotopic map was found, and the right UF responses
      were significantly larger in amplitude than the left UF responses. The half-max
      latency in responses to FM sweeps was shorter in UF compared with that in the
      primary auditory cortex (A1) or anterior auditory field (AAF). Tracer injection
      experiments in the functionally identified UF and DP confirmed that these two
      areas receive afferent inputs from the dorsal part of the medial geniculate
      nucleus (MG). Calcium imaging of UF neurons stained with fura-2 were performed
      using a two-photon microscope, and the presence of UF neurons that were selective
      to both direction and direction reversal of slow frequency modulation was
      demonstrated. These results strongly suggest a role for UF, and possibly DP, as
      cortical areas specialized for processing slow frequency modulation in mice. 

PMID- 23874517
TI  - A multi-metric approach to investigate the effects of weather conditions on the
      demographic of a terrestrial mammal, the european badger (Meles meles).
AB  - Models capturing the full effects of weather conditions on animal populations are
      scarce. Here we decompose yearly temperature and rainfall into mean trends,
      yearly amplitude of change and residual variation, using daily records. We
      establish from multi-model inference procedures, based on 1125 life histories
      (from 1987 to 2008), that European badger (Meles meles) annual mortality and
      recruitment rates respond to changes in mean trends and to variability in
      proximate weather components. Variation in mean rainfall was by far the most
      influential predictor in our analysis. Juvenile survival and recruitment rates
      were highest at intermediate levels of mean rainfall, whereas low adult survival
      rates were associated with only the driest, and not the wettest, years. Both
      juvenile and adult survival rates also exhibited a range of tolerance for
      residual standard deviation around daily predicted temperature values, beyond
      which survival rates declined. Life-history parameters, annual routines and
      adaptive behavioural responses, which define the badgers' climatic niche, thus
      appear to be predicated upon a bounded range of climatic conditions, which
      support optimal survival and recruitment dynamics. That variability in weather
      conditions is influential, in combination with mean climatic trends, on the vital
      rates of a generalist, wide ranging and K-selected medium-sized carnivore, has
      major implications for evolutionary ecology and conservation. 

PMID- 23874518
TI  - Desmoglein-2-integrin Beta-8 interaction regulates actin assembly in endothelial
      cells: deregulation in systemic sclerosis.
AB  - BACKGROUND: The inability of endothelial cells of patients affected by the
      diffuse form of Systemic sclerosis (SSc) to perform angiogenesis is a marker of
      the disease. We previously demonstrated that desmoglein-2 reduction is a major
      difference between (SSc)-microvascular endothelial cells (MVECs) and normal (N)
      MVECs. Here we investigated the role of desmoglein-2 in human N-MVECs and SSc
      MVECs angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Angiogenesis was studied by
      Matrigel invasion, capillary morphogenesis in vitro and Matrigel plug assay in
      vivo. Gene profiling was studied by Affymetrix technology and signal transduction
      by Western blotting. Colocalization was validated by immunoprecipitation and
      confocal microscopy. SiRNAs were used to validate the roles of specific
      molecules. We observed that desmoglein-2 co-localizes with integrin-beta8 in N
      MVECs. This complex is required to signal through Rac, FAK, SMAD1/5 and MAP
      kinases, promoting an angiogenic program. Inhibition of desmoglein-2 by DSG2
      siRNA impaired actin stress fibres formation, capillary morphogenesis in vitro
      and angiogenesis in vivo. Transcriptome profiling after DSG2 inhibition revealed
      alterations of several genes involved in actin organization. siRNA inhibition of
      integrin-beta8 and RAC2 also resulted into capillary morphogenesis impairment in
      N-MVECs, due to reduced expression of the same actin-assembly genes that were
      down-regulated by DSG2 silencing. SSc-MVECs showed down-regulation of the same
      genes in DSG2-siRNA treated N-MVECs, suggesting that impairment of desmoglein
      2/integrin-beta8 complex contributes to angiogenesis derangement in SSc.
      Transfection of DSG2 in SSc-MVEC partially restored their angiogenic properties
      in vitro. CONCLUSIONS/SIGNIFICANCE: We have shown that impairment of actin
      assembly as a result of desmoglein-2/integrin-beta8 complex formation is a major
      factor contributing to angiogenesis deregulation in Systemic sclerosis.

PMID- 23874519
TI  - In vivo function and evolution of the eutherian-specific pluripotency marker
      UTF1.
AB  - Embryogenesis in placental mammals is sustained by exquisite interplay between
      the embryo proper and placenta. UTF1 is a developmentally regulated gene
      expressed in both cell lineages. Here, we analyzed the consequence of loss of the
      UTF1 gene during mouse development. We found that homozygous UTF1 mutant newborn
      mice were significantly smaller than wild-type or heterozygous mutant mice,
      suggesting that placental insufficiency caused by the loss of UTF1 expression in
      extra-embryonic ectodermal cells at least in part contributed to this phenotype.
      We also found that the effects of loss of UTF1 expression in embryonic stem cells
      on their pluripotency were very subtle. Genome structure and sequence comparisons
      revealed that the UTF1 gene exists only in placental mammals. Our analyses of a
      family of genes with homology to UTF1 revealed a possible mechanism by which
      placental mammals have evolved the UTF1 genes. 

PMID- 23874520
TI  - A novel whole-cell mechanism for long-term memory enhancement.
AB  - Olfactory-discrimination learning was shown to induce a profound long-lasting
      enhancement in the strength of excitatory and inhibitory synapses of pyramidal
      neurons in the piriform cortex. Notably, such enhancement was mostly pronounced
      in a sub-group of neurons, entailing about a quarter of the cell population. Here
      we first show that the prominent enhancement in the subset of cells is due to a
      process in which all excitatory synapses doubled their strength and that this
      increase was mediated by a single process in which the AMPA channel conductance
      was doubled. Moreover, using a neuronal-network model, we show how such a
      multiplicative whole-cell synaptic strengthening in a sub-group of cells that
      form a memory pattern, sub-serves a profound selective enhancement of this
      memory. Network modeling further predicts that synaptic inhibition should be
      modified by complex learning in a manner that much resembles synaptic excitation.
      Indeed, in a subset of neurons all GABAA-receptors mediated inhibitory synapses
      also doubled their strength after learning. Like synaptic excitation, Synaptic
      inhibition is also enhanced by two-fold increase of the single channel
      conductance. These findings suggest that crucial learning induces a
      multiplicative increase in strength of all excitatory and inhibitory synapses in
      a subset of cells, and that such an increase can serve as a long-term whole-cell
      mechanism to profoundly enhance an existing Hebbian-type memory. This mechanism
      does not act as synaptic plasticity mechanism that underlies memory formation but
      rather enhances the response of already existing memory. This mechanism is cell
      specific rather than synapse-specific; it modifies the channel conductance rather
      than the number of channels and thus has the potential to be readily induced and
      un-induced by whole-cell transduction mechanisms. 

PMID- 23874521
TI  - Joint and independent effects of alcohol drinking and tobacco smoking on oral
      cancer: a large case-control study.
AB  - Alcohol drinking and tobacco smoking are assumed to have significant independent
      and joint effects on oral cancer (OC) development. This assumption is based on
      consistent reports from observational studies, which, however, overestimated the
      independent effects of smoking and drinking, because they did not account for the
      interaction effect in multivariable analyses. This case-control study sought to
      investigate the independent and the joint effects of smoking and drinking on OC
      in a homogeneous sample of adults. Case patients (N = 1,144) were affected by
      invasive oral/oropharyngeal squamous cell carcinoma confirmed histologically,
      diagnosed between 1998 and 2008 in four hospitals of Sao Paulo (Brazil). Control
      patients (N = 1,661) were not affected by drinking-, smoking-associated diseases,
      cancers, upper aero-digestive tract diseases. Cumulative tobacco and alcohol
      consumptions were assessed anamnestically. Patients were categorized into
      never/ever users and never/level-1/level-2 users, according to the median
      consumption level in controls. The effects of smoking and drinking on OC adjusted
      for age, gender, schooling level were assessed using logistic regression
      analysis; Model-1 did not account for the smoking-drinking interaction; Model-2
      accounted for this interaction and included the resultant interaction terms. The
      models were compared using the likelihood ratio test. According to Model-1, the
      adjusted odds ratios (ORs) for smoking, drinking, smoking-drinking were 3.50 (95%
      confidence interval -95CI, 2.76-4.44), 3.60 (95CI, 2.86-4.53), 12.60 (95CI, 7.89
      20.13), respectively. According to Model-2 these figures were 1.41 (95CI, 1.02
      1.96), 0.78 (95CI, 0.48-1.27), 8.16 (95CI, 2.09-31.78). Analogous results were
      obtained using three levels of exposure to smoking and drinking. Model-2 showed
      statistically significant better goodness-of-fit statistics than Model-1.
      Drinking was not independently associated with OC, while the independent effect
      of smoking was lower than expected, suggesting that observational studies should
      be revised adequately accounting for the smoking-drinking interaction. OC control
      policies should focus on addictive behaviours rather than on single lifestyle
      risk factors. 

PMID- 23874523
TI  - Hydromagnetic steady flow of Maxwell fluid over a bidirectional stretching
      surface with prescribed surface temperature and prescribed surface heat flux.
AB  - This paper investigates the steady hydromagnetic three-dimensional boundary layer
      flow of Maxwell fluid over a bidirectional stretching surface. Both cases of
      prescribed surface temperature (PST) and prescribed surface heat flux (PHF) are
      considered. Computations are made for the velocities and temperatures. Results
      are plotted and analyzed for PST and PHF cases. Convergence analysis is presented
      for the velocities and temperatures. Comparison of PST and PHF cases is given and
      examined. 

PMID- 23874522
TI  - An explosive epidemic of DENV-3 in Cairns, Australia.
AB  - From November 2008-May 2009 Cairns Queensland Australia was struck by an
      explosive epidemic of DENV-3 that exceeded the capacity of highly skilled dengue
      control team to control it. We describe the environmental, virological and
      entomological factors associated with this outbreak to better understand the
      circumstances leading to its occurrence. Patient interviews, serological results
      and viral sequencing strongly suggest that the imported index case was infected
      in Kalimantan, Indonesia. A delay in notification of 27 days from importation of
      the index case until Queensland Health was notified of dengue transmission
      allowed the virus to amplify and spread unchecked through November 2008.
      Unseasonably warm weather, with daily mean temperatures exceeding 30  degrees C,
      occurred in late November and would have shortened the extrinsic incubation
      period of the virus and enhanced transmission. Analysis of case movements early
      in the outbreak indicated that the total incubation period was as low as 9-11
      days. This was supported by laboratory vector competence studies that found
      transmission by Aedes aegypti occurred within 5 days post exposure at 28  degrees
      C. Effective vector competence rates calculated from these transmission studies
      indicate that early transmission contributed to the explosive dengue transmission
      observed in this outbreak. Collections from BG sentinel traps and double sticky
      ovitraps showed that large populations of the vector Ae. aegypti occurred in the
      transmission areas from November - December 2008. Finally, the seasonal movement
      of people around the Christmas holiday season enhanced the spread of DENV-3.
      These results suggest that a strain of DENV-3 with an unusually rapid
      transmission cycle was able to outpace vector control efforts, especially those
      reliant upon delayed action control such as lethal ovitraps.

PMID- 23874524
TI  - Normalizing RNA-sequencing data by modeling hidden covariates with prior
      knowledge.
AB  - Transcriptomic assays that measure expression levels are widely used to study the
      manifestation of environmental or genetic variations in cellular processes. RNA
      sequencing in particular has the potential to considerably improve such
      understanding because of its capacity to assay the entire transcriptome,
      including novel transcriptional events. However, as with earlier expression
      assays, analysis of RNA-sequencing data requires carefully accounting for factors
      that may introduce systematic, confounding variability in the expression
      measurements, resulting in spurious correlations. Here, we consider the problem
      of modeling and removing the effects of known and hidden confounding factors from
      RNA-sequencing data. We describe a unified residual framework that encapsulates
      existing approaches, and using this framework, present a novel method, HCP
      (Hidden Covariates with Prior). HCP uses a more informed assumption about the
      confounding factors, and performs as well or better than existing approaches
      while having a much lower computational cost. Our experiments demonstrate that
      accounting for known and hidden factors with appropriate models improves the
      quality of RNA-sequencing data in two very different tasks: detecting genetic
      variations that are associated with nearby expression variations (cis-eQTLs), and
      constructing accurate co-expression networks. 

PMID- 23874525
TI  - The rs2233678 polymorphism in PIN1 promoter region reduced cancer risk: a meta
      analysis.
AB  - BACKGROUND: Published evidence suggests that the rs2233678 (-842 G>C)
      polymorphism in the PIN1 (peptidyl-prolyl cis/trans somerase NIMA-interacting 1)
      promoter region may be associated with cancer risk; however, the conclusion is
      still inconclusive. METHODS: We conducted a meta-analysis to determine whether 
      842 G>C polymorphism was associated with cancer risk. Odds ratio (OR) and 95%
      confidence intervals (95% CI) were used to assess the strength of association.
      Genotype distribution data and adjusted ORs were collected to calculate the
      pooled ORs. Meta-regression was conducted to detect the source of heterogeneity.
      Publication bias was evaluated by Egger's test and Begg's test. RESULTS: A total
      of 11 eligible studies, including 9280 participants, were identified and
      analyzed. Overall, we found that carriers of the -842 C allele were associated
      with significantly decreased cancer risk (C vs. G, OR = 0.750, 95% CI: 0.639
      0.880, P(heterogeneity )= 0.014, estimated by genotype distribution data; CC+GC
      vs. GG, OR = 0.668, 95% CI: 0.594-0.751, P(heterogeneity) = 0.638, estimated by
      adjusted ORs). No evidence of publication bias was observed. Meta-regression
      revealed that ethnicities (p = 0.021) and sample size (p = 0.02) but not sources
      of control (p = 0.069) were the source of heterogeneity. CONCLUSION: These
      results suggest that the PIN1 rs2233678 (-842 G>C) polymorphism significantly
      reduces cancer risk.

PMID- 23874526
TI  - Evidence of Multiple Disease Resistance (MDR) and implication of meta-analysis in
      marker assisted selection.
AB  - Meta-analysis was performed for three major foliar diseases with the aim to find
      out the total number of QTL responsible for these diseases and depict some real
      QTL for molecular breeding and marker assisted selection (MAS) in maize.
      Furthermore, we confirmed our results with some major known disease resistance
      genes and most well-known gene family of nucleotide binding site (NBS) encoding
      genes. Our analysis revealed that disease resistance QTL were randomly
      distributed in maize genome, but were clustered at different regions of the
      chromosomes. Totally 389 QTL were observed for these three major diseases in
      diverse maize germplasm, out of which 63 QTL were controlling more than one
      disease revealing the presence of multiple disease resistance (MDR). 44 real-QTLs
      were observed based on 4 QTL as standard in a specific region of genome. We also
      confirmed the Ht1 and Ht2 genes within the region of real QTL and 14 NBS-encoding
      genes. On chromosome 8 two NBS genes in one QTL were observed and on chromosome
      3, several cluster and maximum MDR QTL were observed indicating that the apparent
      clustering could be due to genes exhibiting pleiotropic effect. Significant
      relationship was observed between the number of disease QTL and total genes per
      chromosome based on the reference genome B73. Therefore, we concluded that
      disease resistance genes are abundant in maize genome and these results can
      unleash the phenomenon of MDR. Furthermore, these results could be very handy to
      focus on hot spot on different chromosome for fine mapping of disease resistance
      genes and MAS. 

PMID- 23874527
TI  - Suppression of HBV by tenofovir in HBV/HIV coinfected patients: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Hepatitis B coinfection is common in HIV-positive individuals and as
      antiretroviral therapy has made death due to AIDS less common, hepatitis has
      become increasingly important. Several drugs are available to treat hepatitis B.
      The most potent and the one with the lowest risk of resistance appears to be
      tenofovir (TDF). However there are several questions that remain unanswered
      regarding the use of TDF, including the proportion of patients that achieves
      suppression of HBV viral load and over what time, whether suppression is durable
      and whether prior treatment with other HBV-active drugs such as lamivudine,
      compromises the efficacy of TDF due to possible selection of resistant HBV
      strains. METHODS: A systematic review and meta-analysis following PRISMA
      guidelines and using multilevel mixed effects logistic regression, stratified by
      prior and/or concomitant use of lamivudine and/or emtricitabine. RESULTS: Data
      was available from 23 studies including 550 HBV/HIV coinfected patients treated
      with TDF. Follow up was for up to seven years but to ensure sufficient power the
      data analyses were limited to three years. The overall proportion achieving
      suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three
      years, respectively. No effect of prior or concomitant 3TC/FTC was shown.
      Virological rebound on TDF treatment was rare. INTERPRETATION: TDF suppresses HBV
      to undetectable levels in the majority of HBV/HIV coinfected patients with the
      proportion fully suppressed continuing to increase during continuous treatment.
      Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The
      use of combination treatment with 3TC/FTC offers no significant benefit over TDF
      alone.

PMID- 23874528
TI  - Effects of conformism on the cultural evolution of social behaviour.
AB  - Models of cultural evolution study how the distribution of cultural traits
      changes over time. The dynamics of cultural evolution strongly depends on the way
      these traits are transmitted between individuals by social learning. Two
      prominent forms of social learning are payoff-based learning (imitating others
      that have higher payoffs) and conformist learning (imitating locally common
      behaviours). How payoff-based and conformist learning affect the cultural
      evolution of cooperation is currently a matter of lively debate, but few studies
      systematically analyse the interplay of these forms of social learning. Here we
      perform such a study by investigating how the interaction of payoff-based and
      conformist learning affects the outcome of cultural evolution in three social
      contexts. First, we develop a simple argument that provides insights into how the
      outcome of cultural evolution will change when more and more conformist learning
      is added to payoff-based learning. In a social dilemma (e.g. a Prisoner's
      Dilemma), conformism can turn cooperation into a stable equilibrium; in an
      evasion game (e.g. a Hawk-Dove game or a Snowdrift game) conformism tends to
      destabilize the polymorphic equilibrium; and in a coordination game (e.g. a Stag
      Hunt game), conformism changes the basin of attraction of the two equilibria.
      Second, we analyse a stochastic event-based model, revealing that conformism
      increases the speed of cultural evolution towards pure equilibria. Individual
      based simulations as well as the analysis of the diffusion approximation of the
      stochastic model by and large confirm our findings. Third, we investigate the
      effect of an increasing degree of conformism on cultural group selection in a
      group-structured population. We conclude that, in contrast to statements in the
      literature, conformism hinders rather than promotes the evolution of cooperation.

PMID- 23874530
TI  - Characterization of a novel bile alcohol sulfate released by sexually mature male
      sea lamprey (Petromyzon marinus).
AB  - A sulphate-conjugated bile alcohol, 3,12-diketo-4,6-petromyzonene-24-sulfate
      (DKPES), was identified using bioassay-guided fractionation from water
      conditioned with sexually mature male sea lamprey (Petromyzon marinus). The
      structure and relative stereochemistry of DKPES was established using
      spectroscopic data. The electro-olfactogram (EOG) response threshold of DKPES was
      10(-7) Molar (M) and that of 3-keto petromyzonol sulfate (3 KPZS; a known
      component of the male sea lamprey sex pheromone) was 10(-10) M. Behavioural
      studies indicated that DKPES can be detected at low concentrations by attracting
      sexually mature females to nests when combined with 3 KPZS. Nests baited with a
      mixture of DKPES and 3 KPZS (ratio 1?29.8) attracted equal numbers of sexually
      mature females compared to an adjacent nest baited with 3 KPZS alone. When DKPES
      and 3 KPZS mixtures were applied at ratios of 2?29.8 and 10?29.8, the proportion
      of sexually mature females that entered baited nests increased to 73% and 70%,
      respectively. None of the sexually mature females released were attracted to
      nests baited with DKPES alone. These results indicated that DKPES is a component
      of the sex pheromone released by sexually mature male sea lamprey, and is the
      second biologically active compound identified from this pheromone. DKPES
      represents the first example that a minor component of a vertebrate pheromone can
      be combined with a major component to elicit critical sexual behaviors. DKPES
      holds considerable promise for increasing the effectiveness of pheromone-baited
      trapping as a means of sea lamprey control in the Laurentian Great Lakes. 

PMID- 23874529
TI  - N-terminal truncated intracellular matrix metalloproteinase-2 induces
      cardiomyocyte hypertrophy, inflammation and systolic heart failure.
AB  - Matrix metalloproteinase-2 (MMP-2) is increasingly recognized as a major
      contributor to progressive cardiac injury within the setting of ischemia
      reperfusion injury and ischemic ventricular remodeling. A common feature of these
      conditions is an increase in oxidative stress, a process that engages multiple
      pro-inflammatory and innate immunity cascades. We recently reported on the
      identification and characterization of an intracellular isoform of MMP-2
      generated by oxidative stress-mediated activation of an alternative promoter
      located within the first intron of the MMP-2 gene. Transcription from this site
      generates an N-terminal truncated 65 kDa isoform of MMP-2 (NTT-MMP-2) that lacks
      the secretory sequence and the inhibitory prodomain region. The NTT-MMP-2 isoform
      is intracellular, enzymatically active and localizes in part to mitochondria.
      Expression of the NTT-MMP-2 isoform triggers Nuclear Factor of Activated T-cell
      (NFAT) and NF-kappaB signaling with the expression of a highly defined innate
      immunity transcriptome, including Interleukin-6, MCP-1, IRF-7 and pro-apoptotic
      transcripts. To determine the functional significance of the NTT-MMP-2 isoform in
      vivo we generated cardiac-specific NTT-MMP-2 transgenic mice. These mice
      developed progressive cardiomyocyte and ventricular hypertrophy associated with
      systolic heart failure. Further, there was evidence for cardiomyocyte apoptosis
      and myocardial infiltration with mononuclear cells. The NTT-MMP-2 transgenic
      hearts also demonstrated more severe injury following ex vivo ischemia
      reperfusion injury. We conclude that a novel intracellular MMP-2 isoform induced
      by oxidant stress directly contributes, in the absence of superimposed injury, to
      cardiomyocyte hypertrophy. inflammation, systolic heart failure and enhanced
      susceptibility to ischemia-reperfusion injury. 

PMID- 23874531
TI  - Methylation of APC and GSTP1 in non-neoplastic tissue adjacent to prostate tumour
      and mortality from prostate cancer.
AB  - BACKGROUND: Markers that can discriminate between indolent and aggressive
      prostate tumours are needed. We studied gene methylation in non-neoplastic tissue
      adjacent to prostate tumour (NTAT) in association with prostate cancer mortality.
      METHODS: From two cohorts of consecutive prostate cancer patients diagnosed at
      one pathology ward in Turin, Italy, we selected 157 patients with available NTAT
      and followed them up for more than 14 years. We obtained DNA from NTAT in
      paraffin-embedded prostate tumour tissues and used probe real-time PCR to analyse
      methylation of the glutathione S-transferase (GSTP1) and adenomatous polyposis
      coli (APC) gene promoters. RESULTS: Prevalence of APC and GSTP1 methylation in
      the NTAT was between 40 and 45%. It was associated with methylation in prostate
      tumour tissue for the same two genes as well as with a high Gleason score. The
      hazard ratio (HR) of prostate cancer mortality was 2.38 (95% confidence interval:
      1.23-4.61) for APC methylation, and 2.92 (1.49-5.74) for GSTP1 methylation in
      NTAT. It changed to 1.91 (1.03-3.56) and 1.60 (0.80-3.19) after adjusting for
      Gleason score and methylation in prostate tumour tissue. Comparison of 2 vs. 0
      methylated genes in NTAT revealed a HR of 4.30 (2.00-9.22), which decreased to
      2.40 (1.15-5.01) after adjustment. Results were stronger in the first 5 years of
      follow-up (adjusted HR: 3.29, 95% CI: 1.27-8.52). CONCLUSIONS: Changes in gene
      methylation are an early event in prostate carcinogenesis and may play a role in
      cancer progression. Gene methylation in NTAT is a possible prognostic marker to
      be evaluated in clinical studies.

PMID- 23874532
TI  - Evolutionary invasion and escape in the presence of deleterious mutations.
AB  - Replicators such as parasites invading a new host species, species invading a new
      ecological niche, or cancer cells invading a new tissue often must mutate to
      adapt to a new environment. It is often argued that a higher mutation rate will
      favor evolutionary invasion and escape from extinction. However, most mutations
      are deleterious, and even lethal. We study the probability that the lineage will
      survive and invade successfully as a function of the mutation rate when both the
      initial strain and an adaptive mutant strain are threatened by lethal mutations.
      We show that mutations are beneficial, i.e. a non-zero mutation rate increases
      survival compared to the limit of no mutations, if in the no-mutation limit the
      survival probability of the initial strain is smaller than the average survival
      probability of the strains which are one mutation away. The mutation rate that
      maximizes survival depends on the characteristics of both the initial strain and
      the adaptive mutant, but if one strain is closer to the threshold governing
      survival then its properties will have greater influence. These conclusions are
      robust for more realistic or mechanistic depictions of the fitness landscapes
      such as a more detailed viral life history, or non-lethal deleterious mutations. 

PMID- 23874533
TI  - A chinese mind-body exercise improves self-control of children with autism: a
      randomized controlled trial.
AB  - Self-control problems commonly manifest as temper outbursts and
      repetitive/rigid/impulsive behaviors, in children with autism spectrum disorders
      (ASD), which often contributes to learning difficulties and caregiver burden. The
      present study aims to compare the effect of a traditional Chinese Chan-based mind
      body exercise, Nei Yang Gong, with that of the conventional Progressive Muscle
      Relaxation (PMR) technique in enhancing the self-control of children with ASD.
      Forty-six age- and IQ-matched ASD children were randomly assigned to receive
      group training in Nei Yang Gong (experimental group) or PMR (control group) twice
      per week for four weeks. The participants' self-control was measured by three
      neuropsychological tests and parental rating on standardized questionnaires, and
      the underlying neural mechanism was assessed by the participants' brain EEG
      activity during an inhibitory-control task before and after intervention. The
      results show that the experimental group demonstrated significantly greater
      improvement in self-control than the control group, which concurs with the
      parental reports of reduced autistic symptoms and increased control of temper and
      behaviors. In addition, the experimental group showed enhanced EEG activity in
      the anterior cingulate cortex, a region that mediates self-control, whereas the
      PMR group did not. The present findings support the potential application of
      Chinese Chan-based mind-body exercises as a form of neuropsychological
      rehabilitation for patients with self-control problems. Chinese Clinical Trial
      Registry; Registration No.: ChiCTR-TRC-12002561; URL: www.chictr.org. 

PMID- 23874534
TI  - Longitudinal hydrodynamic characteristics in reservoir tributary embayments and
      effects on algal blooms.
AB  - Three Gorges Reservoir (TGR) is one of the largest man-made lakes in the world.
      Since the impoundment in 2003, however, algal blooms have been often observed in
      the tributary embayments. To control the algal blooms, a thorough understanding
      of the hydrodynamics (e.g., flow regime, velocity gradient, and velocity
      magnitude and direction) in the tributary embayments is particularly important.
      Using a calibrated three-dimensional hydrodynamic model, we carried out a
      hydrodynamic analysis of a typical tributary embayment (i.e., Xiangxi Bay) with
      emphasis on the longitudinal patterns. The results show distinct longitudinal
      gradients of hydrodynamics in the study area, which can be generally
      characterized as four zones: riverine, intermediate, lacustrine, and mainstream
      influenced zones. Compared with the typical longitudinal zonation for a pure
      reservoir, there is an additional mainstream influenced zone near the mouth due
      to the strong effects of TGR mainstream. The blooms are prone to occur in the
      intermediate and lacustrine zones; however, the hydrodynamic conditions of
      riverine and mainstream influence zones are not propitious for the formation of
      algal blooms. This finding helps to diagnose the sensitive areas for algal bloom
      occurrence. 

PMID- 23874536
TI  - Comparison of long-term survival of patients with BCLC stage B hepatocellular
      carcinoma after liver resection or transarterial chemoembolization.
AB  - BACKGROUND AND AIMS: Treatment of patients with Barcelona Clinic Liver Cancer
      Stage B hepatocellular carcinoma (BCLC-B HCC) is controversial. This study
      compared the long-term survival of patients with BCLC-B HCC who received liver
      resection (LR) or transarterial chemoembolization (TACE). METHODS: A total of 257
      and 135 BCLC-B HCC patients undergoing LR and TACE, respectively, were
      retrospectively evaluated. Kaplan-Meier method was used for long-term survival
      analysis. Independent prognostic predictors were determined by the Cox
      proportional hazards model. RESULTS: The hospital mortality rate was similar
      between groups (3.1% vs. 3.7%; P = 0.76). However, the LR group showed a
      significantly higher postoperative complication rate than the TACE group (28 vs.
      18.5%; P = 0.04). At the same time, the LR group showed significantly higher
      overall survival rates (1 year, 84 vs. 69%; 3 years, 59 vs. 29%; 5 years, 37 vs.
      14%; P<0.001). Moreover, similar results were observed in the propensity score
      model. Three independent prognostic factors were associated with worse overall
      survival: serum AFP level (>=400 ng/ml), serum ALT level, and TACE. CONCLUSIONS:
      LR appears to be as safe as TACE for patients with BCLC-B HCC, and it provides
      better long-term overall survival. However, prospective studies are needed to
      disclose if LR may be regarded as the preferred treatment for these patients as
      long as liver function is preserved.

PMID- 23874537
TI  - Fully Bayesian inference for structural MRI: application to segmentation and
      statistical analysis of T2-hypointensities.
AB  - Aiming at iron-related T2-hypointensity, which is related to normal aging and
      neurodegenerative processes, we here present two practicable approaches, based on
      Bayesian inference, for preprocessing and statistical analysis of a complex set
      of structural MRI data. In particular, Markov Chain Monte Carlo methods were used
      to simulate posterior distributions. First, we rendered a segmentation algorithm
      that uses outlier detection based on model checking techniques within a Bayesian
      mixture model. Second, we rendered an analytical tool comprising a Bayesian
      regression model with smoothness priors (in the form of Gaussian Markov random
      fields) mitigating the necessity to smooth data prior to statistical analysis.
      For validation, we used simulated data and MRI data of 27 healthy controls (age:
      [Formula: see text]; range, [Formula: see text]). We first observed robust
      segmentation of both simulated T2-hypointensities and gray-matter regions known
      to be T2-hypointense. Second, simulated data and images of segmented T2
      hypointensity were analyzed. We found not only robust identification of simulated
      effects but also a biologically plausible age-related increase of T2
      hypointensity primarily within the dentate nucleus but also within the globus
      pallidus, substantia nigra, and red nucleus. Our results indicate that fully
      Bayesian inference can successfully be applied for preprocessing and statistical
      analysis of structural MRI data. 

PMID- 23874535
TI  - Functional cortical hubs in the eyes-closed resting human brain from an
      electrophysiological perspective using magnetoencephalography.
AB  - It is not clear whether specific brain areas act as hubs in the eyes-closed (EC)
      resting state, which is an unconstrained state free from any passive or active
      tasks. Here, we used electrophysiological magnetoencephalography (MEG) signals to
      study functional cortical hubs in 88 participants. We identified several
      multispectral cortical hubs. Although cortical hubs vary slightly with different
      applied measures and frequency bands, the most consistent hubs were observed in
      the medial and posterior cingulate cortex, the left dorsolateral superior frontal
      cortex, and the left pole of the middle temporal cortex. Hubs were characterized
      as connector nodes integrating EC resting state functional networks. Hubs in the
      gamma band were more likely to include midline structures. Our results confirm
      the existence of multispectral cortical cores in EC resting state functional
      networks based on MEG and imply the existence of optimized functional networks in
      the resting brain. 

PMID- 23874538
TI  - CCN1 secretion induced by cigarette smoking extracts augments IL-8 release from
      bronchial epithelial cells.
AB  - Inflammation involves in many cigarette smoke (CS) related diseases including the
      chronic obstructive pulmonary disease (COPD). Lung epithelial cell released IL-8
      plays a crucial role in CS induced lung inflammation. CS and cigarette smoke
      extracts (CSE) both induce IL-8 secretion and subsequently, IL-8 recruits
      inflammatory cells into the lung parenchyma. However, the molecular and cellular
      mechanisms by which CSE triggers IL-8 release remain not completely understood.
      In this study, we identified a novel extracellular matrix (ECM) molecule, CCN1,
      which mediated CSE induced IL-8 secretion by lung epithelial cells. We first
      found that CS and CSE up-regulated CCN1 expression and secretion in lung
      epithelial cells in vivo and in vitro. CSE up-regulated CCN1 via induction of
      reactive oxygen spices (ROS) and endoplasmic reticulum (ER) stress. p38 MAPK and
      JNK activation were also found to mediate the signal pathways in CSE induced
      CCN1. CCN1 was secreted into ECM via Golgi and membrane channel receptor
      aquaporin4. After CSE exposure, elevated ECM CCN1 functioned via an autocrine or
      paracrine manner. Importantly, CCN1 activated Wnt pathway receptor LRP6,
      subsequently stimulated Wnt pathway component Dvl2 and triggered beta-catenin
      translocation from cell membrane to cytosol and nucleus. Treatment of Wnt pathway
      inhibitor suppressed CCN1 induced IL-8 secretion from lung epithelial cells.
      Taken together, CSE increased CCN1 expression and secretion in lung epithelial
      cells via induction of ROS and ER stress. Increased ECM CCN1 resulted in
      augmented IL-8 release through the activation of Wnt pathway. 

PMID- 23874539
TI  - Transcriptome characterisation of the ant Formica exsecta with new insights into
      the evolution of desaturase genes in social hymenoptera.
AB  - BACKGROUND: Despite the recent sequencing of seven ant genomes, no genomic data
      are available for the genus Formica, an important group for the study of eusocial
      traits. We sequenced the transcriptome of the ant Formica exsecta with the 454
      FLX Titanium technology from a pooled sample of workers from 70 Finnish colonies.
      RESULTS: About 1,000,000 reads were obtained from a normalised cDNA library. We
      compared the assemblers MIRA3.0 and Newbler2.6 and showed that the latter
      performed better on this dataset due to a new option which is dedicated to
      improve contig formation in low depth portions of the assemblies. The 29,579
      contigs represent 27 Mb. 50% showed similarity with known proteins and 25% could
      be assigned a category of gene ontology. We found more than 13,000 high-quality
      single nucleotide polymorphisms. The Delta9 desaturase gene family is an
      important multigene family involved in chemical communication in insects. We
      found six Delta9 desaturases in this Formica exsecta transcriptome dataset that
      were used to reconstruct a maximum-likelihood phylogeny of insect desaturases and
      to test for signatures of positive selection in this multigene family in ant
      lineages. We found differences with previous phylogenies of this gene family in
      ants, and found two clades potentially under positive selection. CONCLUSION: This
      first transcriptome reference sequence of Formica exsecta provided sequence and
      polymorphism data that will allow researchers working on Formica ants to develop
      studies to tackle the genetic basis of eusocial phenotypes. In addition, this
      study provided some general guidelines for de novo transcriptome assembly that
      should be useful for future transcriptome sequencing projects. Finally, we found
      potential signatures of positive selection in some clades of the Delta9
      desaturase gene family in ants, which suggest the potential role of sequence
      divergence and adaptive evolution in shaping the large diversity of chemical cues
      in social insects.

PMID- 23874540
TI  - Identification and characterization of microRNAs from Entamoeba histolytica HM1
      IMSS.
AB  - BACKGROUND: Entamoeba histolytica is the causative agent of amebiasis, a disease
      that is a major source of morbidity and mortality in the developing world.
      MicroRNAs (miRNAs) are a large group of non-coding RNAs that play important roles
      in regulating gene expression and protein translation in animals. Genome-wide
      identification of miRNAs is a critical step to facilitating our understanding of
      genome organization, genome biology, evolution, and post-transcriptional
      regulation. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced a small RNA library
      prepared from a culture of trophozoites of Entamoeba histolytica Strain HM1-IMSS
      using a deep DNA sequencing approach. Deep sequencing yielded 16 million high
      quality short sequence reads containing a total of 5 million non-redundant
      sequence reads. Based on a bioinformatics pipeline, we found that only 0.5% of
      these non-redundant small RNA reads were a perfect match with the drafted E.
      histolytica genome. We did not find miRNA homologs in plant or animal miRNAs. We
      discovered 199 new potential Entamoeba histolytica miRNAs. The expression and
      sequence of these Ehi-miRNAs were further validated through microarray by
      uParaflo Microfluidic Biochip Technology. Ten potential miRNAs were additionally
      confirmed by real time RT-PCR analysis. Prediction of target genes matched 32
      known genes and 34 hypothetical genes. CONCLUSIONS/SIGNIFICANCE: These results
      show that there is a number of regulatory miRNAs in Entamoeba histolytica. The
      collection of miRNAs in this parasite could be used as a new platform to study
      genomic structure, gene regulation and networks, development, and host-parasite
      interactions.

PMID- 23874541
TI  - A re-emerging marker for prognosis in hepatocellular carcinoma: the add-value of
      fishing c-myc gene for early relapse.
AB  - Hepatocellular carcinoma is one leading cause of cancer-related death and
      surgical resection is still one of the major curative therapies. Recently, there
      has been a major effort to find mechanisms involved in carcinogenesis and early
      relapse. c-myc gene abnormality is found in hepatocarcinogenesis. Our aim was to
      analyze the role of c-myc as prognostic factor in terms of overall survival and
      disease-free survival and to investigate if c-myc may be an important target for
      therapy. We studied sixty-five hepatocellular carcinomas submitted to surgical
      resection with curative intent. Size, macro-microvascular invasion, necrosis,
      number of nodules, grading and serum alfa-fetoprotein level were registered for
      all cases. We evaluated the c-myc aberrations by using break-apart FISH probes.
      Probes specific for the centromeric part of chromosome 8 and for the locus
      specific c-myc gene (8q24) were used to assess disomy, gains of chromosomes
      (polysomy due to polyploidy) and amplification. c-myc gene amplification was
      scored as 8q24/CEP8 > 2. Statistical analysis for disease-free survival and
      overall survival were performed. At molecular level, c-myc was amplified in 19%
      of hepatocellular carcinoma, whereas showed gains in 55% and set wild in 26% of
      cases. The 1- and 3-year disease-free survival and overall survival for disomic,
      polysomic and amplified groups were significantly different (p=0.020 and p=.018
      respectively). Multivariate analysis verified that the AFP and c-myc status
      (amplified vs. not amplified) were significant prognostic factors for overall
      patients survival. c-myc gene amplification is significantly correlated with
      disease-free survival and overall survival in patients with hepatocellular
      carcinoma after surgical resection and this model identifies patients with risk
      of early relapse (<=12 months). We suggest that c-myc assessment may be
      introduced in the clinical practice for improving prognostication (high and low
      risk of relapse) routinely and may have be proposed as biomarker of efficacy to
      anti-c-myc targeted drugs in clinical trials. 

PMID- 23874542
TI  - Large-scale screens of miRNA-mRNA interactions unveiled that the 3'UTR of a gene
      is targeted by multiple miRNAs.
AB  - Animal microRNA (miRNA) target prediction is still a challenge, although many
      prediction programs have been exploited. MiRNAs exert their function through
      partially binding the messenger RNAs (mRNAs; likely at 3' untranslated regions
      [3'UTRs]), which makes it possible to detect the miRNA-mRNA interactions in vitro
      by co-transfection of miRNA and a luciferase reporter gene containing the target
      mRNA fragment into mammalian cells under a dual-luciferase assay system. Here, we
      constructed a human miRNA expression library and used a dual-luciferase assay
      system to perform large-scale screens of interactions between miRNAs and the
      3'UTRs of seven genes, which included more than 3,000 interactions with
      triplicate experiments for each interaction. The screening results showed that
      the 3'UTR of one gene can be targeted by multiple miRNAs. Among the prediction
      algorithms, a Bayesian phylogenetic miRNA target identification algorithm and a
      support vector machine (SVM) presented a relatively better performance (27% for
      EIMMo and 24.7% for miRDB) against the average precision (17.3%) of the nine
      prediction programs used here. Additionally, we noticed that a relatively high
      conservation level was shown at the miRNA 3' end targeted regions, as well as the
      5' end (seed region) binding sites. 

PMID- 23874543
TI  - Identifying neural patterns of functional dyspepsia using multivariate pattern
      analysis: a resting-state FMRI study.
AB  - BACKGROUND: Previous imaging studies on functional dyspepsia (FD) have focused on
      abnormal brain functions during special tasks, while few studies concentrated on
      the resting-state abnormalities of FD patients, which might be potentially
      valuable to provide us with direct information about the neural basis of FD. The
      main purpose of the current study was thereby to characterize the distinct
      patterns of resting-state function between FD patients and healthy controls
      (HCs). METHODOLOGY/PRINCIPAL FINDINGS: Thirty FD patients and thirty HCs were
      enrolled and experienced 5-mintue resting-state scanning. Based on the support
      vector machine (SVM), we applied multivariate pattern analysis (MVPA) to
      investigate the differences of resting-state function mapped by regional
      homogeneity (ReHo). A classifier was designed by using the principal component
      analysis and the linear SVM. Permutation test was then employed to identify the
      significant contribution to the final discrimination. The results displayed that
      the mean classifier accuracy was 86.67%, and highly discriminative brain regions
      mainly included the prefrontal cortex (PFC), orbitofrontal cortex (OFC),
      supplementary motor area (SMA), temporal pole (TP), insula, anterior/middle
      cingulate cortex (ACC/MCC), thalamus, hippocampus (HIPP)/parahippocamus
      (ParaHIPP) and cerebellum. Correlation analysis revealed significant correlations
      between ReHo values in certain regions of interest (ROI) and the FD symptom
      severity and/or duration, including the positive correlations between the dmPFC,
      pACC and the symptom severity; whereas, the positive correlations between the
      MCC, OFC, insula, TP and FD duration. CONCLUSIONS: These findings indicated that
      significantly distinct patterns existed between FD patients and HCs during the
      resting-state, which could expand our understanding of the neural basis of FD.
      Meanwhile, our results possibly showed potential feasibility of functional
      magnetic resonance imaging diagnostic assay for FD.

PMID- 23874544
TI  - The metastasis suppressor, N-myc downregulated gene 1 (NDRG1), is a prognostic
      biomarker for human colorectal cancer.
AB  - Metastasis remains to be one of the most prevalent causes leading to poor long
      term survival of colorectal cancer (CRC) patients. The clinical significances of
      tumor metastatic suppressor, N-myc downregulated gene 1 (NDRG1), have been
      inconsistently reported in a variety of cancerous diseases. In this study with
      240 CRC clinical specimens, we showed that NDRG1 expression was significantly
      decreased in most of CRC tissues compared to the paired non-tumor counterparts.
      Statistical analysis revealed a significant inverse correlation of NDRG1
      expression with tumor stage, differentiation status and metastasis. Compared with
      NDRG1-negative group, NDRG1-positve group had better disease-free/overall
      survival (p = 0.000) over 5 years' follow-up. Furthermore, NDRG1 was considered
      to be an independent prognostic factor for overall survival (p = 0.001) and
      recurrence (p = 0.003). Our study concludes that NDRG1 is a novel favorable
      predictor for the prognosis in CRC patients. 

PMID- 23874545
TI  - COX-2-derived prostanoids and oxidative stress additionally reduce endothelium
      mediated relaxation in old type 2 diabetic rats.
AB  - Endothelial dysfunction in resistance arteries alters end organ perfusion in type
      2 diabetes. Superoxides and cyclooxygenase-2 (COX-2) derivatives have been shown
      separately to alter endothelium-mediated relaxation in aging and diabetes but
      their role in the alteration of vascular tone in old diabetic subjects is not
      clear, especially in resistance arteries. Consequently, we investigated the role
      of superoxide and COX-2-derivatives on endothelium-dependent relaxation in 3 and
      12 month-old Zucker diabetic fatty (ZDF) and lean (LZ) rats. Mesenteric
      resistance arteries were isolated and vascular tone was investigated using wire
      myography. Endothelium (acetylcholine)-dependent relaxation was lower in ZDF than
      in LZ rats (60 versus 84% maximal relaxation in young rats and 41 versus 69% in
      old rats). Blocking NO production with L-NAME was less efficient in old than in
      young rats. L-NAME had no effect in old ZDF rats although eNOS expression level
      in old ZDF rats was similar to that in old LZ rats. Superoxide level and NADPH
      oxidase subunits (p67phox and gp91phox) expression level were greater in ZDF than
      in LZ rats and were further increased by aging in ZDF rats. In young ZDF rats
      reducing superoxide level with tempol restored acetylcholine-dependent relaxation
      to the level of LZ rats. In old ZDF rats tempol improved acetylcholine-dependent
      relaxation without increasing it to the level of LZ rats. COX-2 (immunolabelling
      and Western-blot) was present in arteries of ZDF rats and absent in LZ rats. In
      old ZDF rats arterial COX-2 level was higher than in young ZDF rats. COX-2
      blockade with NS398 restored in part acetylcholine-dependent relaxation in
      arteries of old ZDF rats and the combination of tempol and NS398 fully restored
      relaxation in control (LZ rats) level. Accordingly, superoxide production and COX
      2 derivatives together reduced endothelium-dependent relaxation in old ZDF rats
      whereas superoxides alone attenuated relaxation in young ZDF or old LZ rats. 

PMID- 23874546
TI  - Identification of biomarkers of response to IFNg during endotoxin tolerance:
      application to septic shock.
AB  - The rapid development in septic patients of features of marked immunosuppression
      associated with increased risk of nosocomial infections and mortality represents
      the rational for the initiation of immune targeted treatments in sepsis. However,
      as there is no clinical sign of immune dysfunctions, the current challenge is to
      develop biomarkers that will help clinicians identify the patients that would
      benefit from immunotherapy and monitor its efficacy. Using an in vitro model of
      endotoxin tolerance (ET), a pivotal feature of sepsis-induced immunosuppression
      in monocytes, we identified using gene expression profiling by microarray a panel
      of transcripts associated with the development of ET which expression was
      restored after immunostimulation with interferon-gamma (IFN-gamma). These results
      were confirmed by qRT-PCR. Importantly, this short-list of markers was further
      evaluated in patients. Of these transcripts, six (TNFAIP6, FCN1, CXCL10, GBP1,
      CXCL5 and PID1) were differentially expressed in septic patients' blood compared
      to healthy blood upon ex vivo LPS stimulation and were restored by IFN-gamma. In
      this study, by combining a microarray approach in an in vitro model and a
      validation in clinical samples, we identified a panel of six new transcripts that
      could be used for the identification of septic patients eligible for IFNg
      therapy. Along with the previously identified markers TNFa, IL10 and HLA-DRA, the
      potential value of these markers should now be evaluated in a larger cohort of
      patients. Upon favorable results, they could serve as stratification tools prior
      to immunostimulatory treatment and to monitor drug efficacy. 

PMID- 23874547
TI  - Interleukin-13 -1112 C/T promoter polymorphism confers risk for COPD: a meta
      analysis.
AB  - BACKGROUND: Interleukin (IL)-13, a T-helper type 2 cytokine, plays a critical
      role in the development of chronic obstructive pulmonary disease (COPD). This
      meta-analysis was performed to assess the association of IL-13 -1112 C/T promoter
      polymorphism with COPD susceptibility. METHODS: Published case-control studies
      from Pubmed and China National Knowledge Infrastructure (CNKI) databases were
      retrieved. Data were extracted and pooled odds ratios (OR) with 95% confidence
      intervals (CI) were calculated. RESULTS: Eight case-control studies in seven
      articles were included in this meta-analysis. Pooled effect size showed IL-13 
      1112 C/T was associated with COPD susceptibility in a codominant genetic model
      (TT vs CT, OR: 1.82, 95% CI: 1.14-2.92 and TT vs CC, OR: 2.02, 95% CI: 1.10
      3.72), indicating individuals with TT genotype had an increased risk for COPD
      compared with those with CT or CC genotype. According to ethnicity, results
      indicated IL-13 -1112 C/T was correlated with COPD susceptibility in Arabians (TT
      vs CT, OR: 2.94, 95% CI: 1.03-8.42 and TT vs CC, OR: 3.05, 95% CI: 1.08-8.59).
      Moreover, after excluding the study without Hardy-Weinberg equilibrium, the
      pooled results were robust and no publication bias was found in this study.
      CONCLUSIONS: This meta-analysis suggests IL-13 -1112 C/T promoter polymorphism is
      associated with the risk of COPD in Arabians.

PMID- 23874548
TI  - Smokeless tobacco extract (STE)-induced toxicity in mammalian cells is mediated
      by the disruption of cellular microtubule network: a key mechanism of
      cytotoxicity.
AB  - Smokeless tobacco usage is a growing public health problem worldwide. The
      molecular mechanism(s) underlying smokeless tobacco associated tissue damage
      remain largely unidentified. In the present study we have tried to explore the
      effects of aqueous extract of smokeless tobacco (STE) on tubulin-microtubule, the
      major cytoskeleton protein that maintains cells morphology and participates in
      cell division. Exposure to STE resulted in dose-dependent cytotoxicity in a
      variety of mammalian transformed cell lines such as human lung epithelial cells
      A549, human liver epithelial cells HepG2, and mouse squamous epithelial cells
      SCC7, [corrected] as well as non-tumorogenic human peripheral blood mononuclear
      cells PBMC. Cellular morphology of STE-treated cells was altered and the
      associated disruption of microtubule network indicates that STE targets tubulin
      microtubule system in both cell lines. Furthermore it was also observed that STE
      treatment resulted in the selective degradation of cellular tubulin, whereas
      actin remains unaltered. In vitro, polymerization of purified tubulin was
      inhibited by STE with the IC50 value~150 ug/ml and this is associated with the
      loss of reactive cysteine residues of tubulin. Application of thiol-based
      antioxidant N-acetyl cysteine (NAC) significantly abrogates STE-mediated
      microtubule damage and associated cytotoxicity in both A549 and HepG2 cells.
      These results suggest that microtubule damage is one of the key mechanisms of STE
      induced cytotoxity in mammalian cells.

PMID- 23874549
TI  - The predicted influence of climate change on lesser prairie-chicken reproductive
      parameters.
AB  - The Southern High Plains is anticipated to experience significant changes in
      temperature and precipitation due to climate change. These changes may influence
      the lesser prairie-chicken (Tympanuchus pallidicinctus) in positive or negative
      ways. We assessed the potential changes in clutch size, incubation start date,
      and nest survival for lesser prairie-chickens for the years 2050 and 2080 based
      on modeled predictions of climate change and reproductive data for lesser prairie
      chickens from 2001-2011 on the Southern High Plains of Texas and New Mexico. We
      developed 9 a priori models to assess the relationship between reproductive
      parameters and biologically relevant weather conditions. We selected weather
      variable(s) with the most model support and then obtained future predicted values
      from climatewizard.org. We conducted 1,000 simulations using each reproductive
      parameter's linear equation obtained from regression calculations, and the future
      predicted value for each weather variable to predict future reproductive
      parameter values for lesser prairie-chickens. There was a high degree of model
      uncertainty for each reproductive value. Winter temperature had the greatest
      effect size for all three parameters, suggesting a negative relationship between
      above-average winter temperature and reproductive output. The above-average
      winter temperatures are correlated to La Nina events, which negatively affect
      lesser prairie-chickens through resulting drought conditions. By 2050 and 2080,
      nest survival was predicted to be below levels considered viable for population
      persistence; however, our assessment did not consider annual survival of adults,
      chick survival, or the positive benefit of habitat management and conservation,
      which may ultimately offset the potentially negative effect of drought on nest
      survival. 

PMID- 23874550
TI  - Surgical treatment for patients with Krukenberg tumor of stomach origin: clinical
      outcome and prognostic factors analysis.
AB  - Krukenberg tumor originated from stomach in female patients is common in clinical
      practice, but it is still uncertain whether surgical resection of ovarian
      metastases could improve the outcome. Some studies suggested that a certain group
      of patients could benefit from the resection of ovarian metastases. However,
      conclusions were different between studies and there was no data to illustrate if
      certain molecular markers were associated with patients' survival. In this study,
      we analyzed the effects of resection of ovarian metastases, and investigated
      prognostic factors in 133 patients with ovarian metastases originated from
      stomach. Furthermore, we examined the expression of some cancer stem cells (CSCs)
      markers or related molecules in 64 ovarian metastases specimens and analyzed the
      correlation between these molecules and patients' survival. We found that the
      median overall survival (mOS) of all 133 patients was 16 months, and
      "gastrectomy" and "without ascites" were two independent prognostic factors
      associated with longer survival. The mOS of the patients with gastrectomy was
      longer than that of patients had not undergone gastrectomy (19 vs. 9 months, p =
      0.048). Patients without ascites survived longer than those with ascites (mOS: 21
      vs. 13 months, p = 0.008). We also found that Sox2, CD44 or CD133 positive
      expression in ovarian metastases were risk factors correlated with poor survival,
      and Sox2 expression was an independent prognostic indicator. These results
      suggested that ovarian metastasectomy might help to prolong the survivor of some
      patients with Krukenberg tumor originated from stomach. Patients without ascites,
      and with resected or resectable primary gastric cancer lesion could get benefit
      from and be potential candidate for surgical treatment. The expression of Sox2
      might serve as a prognostic indicator for predicting patients' survival and be
      helpful for selecting patients in future. 

PMID- 23874551
TI  - Evaluation of reference genes for RT-qPCR expression studies in hop (Humulus
      lupulus L.) during infection with vascular pathogen verticillium albo-atrum.
AB  - Hop plant (Humulus lupulus L.), cultivated primarily for its use in the brewing
      industry, is faced with a variety of diseases, including severe vascular
      diseases, such as Verticillium wilt, against which no effective protection is
      available. The understanding of disease resistance with tools such as
      differentially expressed gene studies is an important objective of plant defense
      mechanisms. In this study, we evaluated twenty-three reference genes for RT-qPCR
      expression studies on hop under biotic stress conditions. The candidate genes
      were validated on susceptible and resistant hop cultivars sampled at three
      different time points after infection with Verticillium albo-atrum. The stability
      of expression and the number of genes required for accurate normalization were
      assessed by three different Excel-based approaches (geNorm v.3.5 software,
      NormFinder, and RefFinder). High consistency was found among them, identifying
      the same six best reference genes (YLS8, DRH1, TIP41, CAC, POAC and SAND) and
      five least stably expressed genes (CYCL, UBQ11, POACT, GAPDH and NADH). The
      candidate genes in different experimental subsets/conditions resulted in
      different rankings. A combination of the two best reference genes, YLS8 and DRH1,
      was used for normalization of RT-qPCR data of the gene of interest (PR-1)
      implicated in biotic stress of hop. We outlined the differences between
      normalized and non-normalized values and the importance of RT-qPCR data
      normalization. The high correlation obtained among data standardized with
      different sets of reference genes confirms the suitability of the reference genes
      selected for normalization. Lower correlations between normalized and non
      normalized data may reflect different quantity and/or quality of RNA samples used
      in RT-qPCR analyses. 

PMID- 23874552
TI  - Identification and effect decomposition of risk factors for Brucella
      contamination of raw whole milk in china.
AB  - BACKGROUND: Lack of clear risk factor identification is the main reason for the
      persistence of brucellosis infection in the Chinese population, and there has
      been little assessment of the factors contributing to Brucella contamination of
      raw whole milk. The purpose of this study was to identify risk factors affecting
      Brucella contamination of raw milk, and to evaluate effective measures for
      disease reduction in order to determine preventive strategies. METHODS AND
      FINDINGS: A nationwide survey was conducted and samples were obtained from 5211
      cows corresponding to 25 sampling locations throughout 15 provinces in China. The
      prevalence of Brucella in the raw milk samples averaged 1.07% over the 15 Chinese
      provinces, while the prevalence of positive areas within these regions ranged
      from 0.23-3.84% among the nine provinces with positive samples. The survey
      examined factors that supposedly influence Brucella contamination of raw whole
      milk, such as management style, herd size, abortion rate, hygiene and disease
      control practices. A binary logistic regression analysis was carried out to
      determine the association between risk factors for Brucella and contamination of
      milk samples. Furthermore, a relative effect decomposition study was conducted to
      determine effective strategies for reducing the risk of Brucella contamination of
      raw whole milk. Our data indicate that disease prevention and control measures,
      abortion rate, and animal polyculture are the most important risk factors.
      Meanwhile, culling after quarantine was identified as an effective protective
      measure in the current Chinese dairy situation. CONCLUSIONS: These results
      indicate that, although there is a low risk of contamination of milk with
      Brucella nationwide in China, there are individual regions where contamination is
      a significant problem. Controlling three factors-culling after quarantine,
      maintaining a low abortion rate, and avoiding mixing groups of cattle and small
      ruminants-could effectively reduce the risk of Brucella contamination of raw
      whole milk.

PMID- 23874554
TI  - Still acting green: continued expression of photosynthetic genes in the
      heterotrophic Dinoflagellate Pfiesteria piscicida (Peridiniales, Alveolata).
AB  - The loss of photosynthetic function should lead to the cessation of expression
      and finally loss of photosynthetic genes in the new heterotroph. Dinoflagellates
      are known to have lost their photosynthetic ability several times.
      Dinoflagellates have also acquired photosynthesis from other organisms, either on
      a long-term basis or as "kleptoplastids" multiple times. The fate of
      photosynthetic gene expression in heterotrophs can be informative into evolution
      of gene expression patterns after functional loss, and the dinoflagellates
      ability to acquire new photosynthetic function through additional endosymbiosis.
      To explore this we analyzed a large-scale EST database consisting of 151,091
      unique sequences (29,170 contigs, 120,921 singletons) obtained from 454
      pyrosequencing of the heterotrophic dinoflagellate Pfiesteria piscicida. About
      597 contigs from P. piscicida showed significant homology (E-value <e(-30)) with
      proteins associated with plastid and photosynthetic function. Most of the genes
      involved in the Calvin-Benson cycle were found, genes of the light-dependent
      reaction were also identified. Also genes of associated pathways including the
      chorismate pathway and genes involved in starch metabolism were discovered. BLAST
      searches and phylogenetic analysis suggest that these plastid-associated genes
      originated from several different photosynthetic ancestors. The Calvin-Benson
      cycle genes are mostly associated with genes derived from the secondary plastids
      of peridinin-containing dinoflagellates, while the light-harvesting genes are
      derived from diatoms, or diatoms that are tertiary plastids in other
      dinoflagellates. The continued expression of many genes involved in
      photosynthetic pathways indicates that the loss of transcriptional regulation may
      occur well after plastid loss and could explain the organism's ability to
      "capture" new plastids (i.e. different secondary endosymbiosis or tertiary
      symbioses) to renew photosynthetic function. 

PMID- 23874553
TI  - Stevens-johnson syndrome associated with drugs and vaccines in children: a case
      control study.
AB  - OBJECTIVE: Stevens-Johnson Syndrome (SJS) is one of the most severe muco
      cutaneous diseases and its occurrence is often attributed to drug use. The aim of
      the present study is to quantify the risk of SJS in association with drug and
      vaccine use in children. METHODS: A multicenter surveillance of children
      hospitalized through the emergency departments for acute conditions of interest
      is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from
      all admissions. Parents were interviewed on child's use of drugs and vaccines
      preceding the onset of symptoms that led to the hospitalization. We compared the
      use of drugs and vaccines in cases with the corresponding use in a control group
      of children hospitalized for acute neurological conditions. RESULTS: Twenty-nine
      children with a diagnosis of SJS and 1,362 with neurological disorders were
      hospitalized between 1(st) November 1999 and 31(st) October 2012. Cases were more
      frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4;
      95% CI 1.0-6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI
      8.4-86.0). Significantly elevated risks were also estimated for antibiotics use
      (adjusted OR 3.3; 95% CI 1.5-7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8
      9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5-6.9). No increased risk was
      estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3-2.8). DISCUSSION: Our study
      provides additional evidence on the etiologic role of drugs and vaccines in the
      occurrence of SJS in children.

PMID- 23874555
TI  - Transcriptome analysis and discovery of genes involved in immune pathways from
      hepatopancreas of microbial challenged mitten crab Eriocheir sinensis.
AB  - BACKGROUND: The Chinese mitten crab Eriocheir sinensis is an important economic
      crustacean and has been seriously attacked by various diseases, which requires
      more and more information for immune relevant genes on genome background.
      Recently, high-throughput RNA sequencing (RNA-seq) technology provides a powerful
      and efficient method for transcript analysis and immune gene discovery.
      METHODS/PRINCIPAL FINDINGS: A cDNA library from hepatopancreas of E. sinensis
      challenged by a mixture of three pathogen strains (Gram-positive bacteria
      Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia
      pastoris; 10(8) cfu.mL(-1)) was constructed and randomly sequenced using Illumina
      technique. Totally 39.76 million clean reads were assembled to 70,300 unigenes.
      After ruling out short-length and low-quality sequences, 52,074 non-redundant
      unigenes were compared to public databases for homology searching and 17,617 of
      them showed high similarity to sequences in NCBI non-redundant protein (Nr)
      database. For function classification and pathway assignment, 18,734 (36.00%)
      unigenes were categorized to three Gene Ontology (GO) categories, 12,243 (23.51%)
      were classified to 25 Clusters of Orthologous Groups (COG), and 8,983 (17.25%)
      were assigned to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
      Potentially, 24, 14, 47 and 132 unigenes were characterized to be involved in
      Toll, IMD, JAK-STAT and MAPK pathways, respectively. CONCLUSIONS/SIGNIFICANCE:
      This is the first systematical transcriptome analysis of components relating to
      innate immune pathways in E. sinensis. Functional genes and putative pathways
      identified here will contribute to better understand immune system and prevent
      various diseases in crab.

PMID- 23874556
TI  - Model-based simulation and prediction of an antiviral strategy against influenza
      A infection.
AB  - There is a strong need to develop novel strategies in using antiviral agents to
      efficiently treat influenza infections. Thus, we constructed a rule-based
      mathematical model that reflects the complicated interactions of the host
      immunity and viral life cycle and analyzed the key controlling steps of influenza
      infections. The main characteristics of the pandemic and seasonal influenza
      strains were estimated using parameter values derived from cells infected with
      Influenza A/California/04/2009 and Influenza A/NewCaledonia/20/99, respectively.
      The quantitative dynamics of the infected host cells revealed a more aggressive
      progression of the pandemic strain than the seasonal strain. The perturbation of
      each parameter in the model was then tested for its effects on viral production.
      In both the seasonal and pandemic strains, the inhibition of the viral release
      (kC), the reinforcement of viral attachment (kV), and an increased transition
      rate of infected cells into activated cells (kI) exhibited significant
      suppression effects on the viral production; however, these inhibitory effects
      were only observed when the numerical perturbations were performed at the early
      stages of the infection. In contrast, combinatorial perturbations of both the
      inhibition of viral release and either the reinforcement of the activation of
      infected cells or the viral attachment exhibited a significant reduction in the
      viral production even at a later stage of infection. These results suggest that,
      in addition to blocking the viral release, a combination therapy that also
      enhances either the viral attachment or the transition of the infected cells
      might provide an alternative for effectively controlling progressed influenza
      infection.

PMID- 23874557
TI  - Oral delivery of lipophilic drugs: the tradeoff between solubility increase and
      permeability decrease when using cyclodextrin-based formulations.
AB  - The purpose of this study was to investigate the impact of oral cyclodextrin
      based formulation on both the apparent solubility and intestinal permeability of
      lipophilic drugs. The apparent solubility of the lipophilic drug dexamethasone
      was measured in the presence of various HPbetaCD levels. The drug's permeability
      was measured in the absence vs. presence of HPbetaCD in the rat intestinal
      perfusion model, and across Caco-2 cell monolayers. The role of the unstirred
      water layer (UWL) in dexamethasone's absorption was studied, and a simplified
      mass-transport analysis was developed to describe the solubility-permeability
      interplay. The PAMPA permeability of dexamethasone was measured in the presence
      of various HPbetaCD levels, and the correlation with the theoretical predictions
      was evaluated. While the solubility of dexamethasone was greatly enhanced by the
      presence of HPbetaCD (K1:1 = 2311 M(-1)), all experimental models showed that the
      drug's permeability was significantly reduced following the cyclodextrin
      complexation. The UWL was found to have no impact on the absorption of
      dexamethasone. A mass transport analysis was employed to describe the solubility
      permeability interplay. The model enabled excellent quantitative prediction of
      dexamethasone's permeability as a function of the HPbetaCD level. This work
      demonstrates that when using cyclodextrins in solubility-enabling formulations, a
      tradeoff exists between solubility increase and permeability decrease that must
      not be overlooked. This tradeoff was found to be independent of the unstirred
      water layer. The transport model presented here can aid in striking the
      appropriate solubility-permeability balance in order to achieve optimal overall
      absorption.

PMID- 23874558
TI  - Curve fitting of the corporate recovery rates: the comparison of Beta
      distribution estimation and kernel density estimation.
AB  - Recovery rate is essential to the estimation of the portfolio's loss and economic
      capital. Neglecting the randomness of the distribution of recovery rate may
      underestimate the risk. The study introduces two kinds of models of distribution,
      Beta distribution estimation and kernel density distribution estimation, to
      simulate the distribution of recovery rates of corporate loans and bonds. As is
      known, models based on Beta distribution are common in daily usage, such as
      CreditMetrics by J.P. Morgan, Portfolio Manager by KMV and Losscalc by Moody's.
      However, it has a fatal defect that it can't fit the bimodal or multimodal
      distributions such as recovery rates of corporate loans and bonds as Moody's new
      data show. In order to overcome this flaw, the kernel density estimation is
      introduced and we compare the simulation results by histogram, Beta distribution
      estimation and kernel density estimation to reach the conclusion that the
      Gaussian kernel density distribution really better imitates the distribution of
      the bimodal or multimodal data samples of corporate loans and bonds. Finally, a
      Chi-square test of the Gaussian kernel density estimation proves that it can fit
      the curve of recovery rates of loans and bonds. So using the kernel density
      distribution to precisely delineate the bimodal recovery rates of bonds is
      optimal in credit risk management. 

PMID- 23874559
TI  - Identification of a novel cetacean polyomavirus from a common dolphin (Delphinus
      delphis) with Tracheobronchitis.
AB  - A female short-beaked common dolphin calf was found stranded in San Diego,
      California in October 2010, presenting with multifocal ulcerative lesions in the
      trachea and bronchi. Viral particles suggestive of polyomavirus were detected by
      EM, and subsequently confirmed by PCR and sequencing. Full genome sequencing (Ion
      Torrent) revealed a circular dsDNA genome of 5,159 bp that was shown to form a
      distinct lineage within the genus Polyomavirus based on phylogenetic analysis of
      the early and late transcriptomes. Viral infection and distribution in laryngeal
      mucosa was characterised using in-situ hybridisation, and apoptosis observed in
      the virus-infected region. These results demonstrate that polyomaviruses can be
      associated with respiratory disease in cetaceans, and expand our knowledge of
      their diversity and clinical significance in marine mammals. 

PMID- 23874560
TI  - The Myxococcus xanthus two-component system CorSR regulates expression of a gene
      cluster involved in maintaining copper tolerance during growth and development.
AB  - Myxococcus xanthus is a soil-dwelling member of the delta-Proteobacteria that
      exhibits a complex developmental cycle upon starvation. Development comprises
      aggregation and differentiation into environmentally resistant myxospores in an
      environment that includes fluctuations in metal ion concentrations. While copper
      is essential for M. xanthus cells because several housekeeping enzymes use it as
      a cofactor, high copper concentrations are toxic. These opposing effects force
      cells to maintain a tight copper homeostasis. A plethora of paralogous genes
      involved in copper detoxification, all of which are differentially regulated,
      have been reported in M. xanthus. The use of in-frame deletion mutants and
      fusions with the reporter gene lacZ has allowed the identification of a two
      component system, CorSR, that modulates the expression of an operon termed curA
      consisting of nine genes whose expression slowly increases after metal addition,
      reaching a plateau. Transcriptional regulation of this operon is complex because
      transcription can be initiated at different promoters and by different types of
      regulators. These genes confer copper tolerance during growth and development.
      Copper induces carotenoid production in a DeltacorSR mutant at lower
      concentrations than with the wild-type strain due to lack of expression of a gene
      product resembling subunit III of cbb3-type cytochrome c oxidase. This data may
      explain why copper induces carotenoid biosynthesis at suboptimal rather than
      optimal growth conditions in wild-type strains. 

PMID- 23874561
TI  - New metrics for comparison of taxonomies reveal striking discrepancies among
      species delimitation methods in Madascincus lizards.
AB  - Delimiting and describing species is fundamental to numerous biological
      disciplines such as evolution, macroecology, and conservation. Delimiting species
      as independent evolutionary lineages may and often does yield different outcomes
      depending on the species criteria applied, but methods should be chosen that
      minimize the inference of objectively erroneous species limits. Several protocols
      exploit single-gene or multi-gene coalescence statistics, assignment tests or
      other rationales related to nuclear DNA (nDNA) allele sharing to automatically
      delimit species. We apply seven different species delimitation protocols to a
      taxonomically confusing group of Malagasy lizards (Madascincus), and compare the
      resulting taxonomies with two newly developed metrics: the Taxonomic index of
      congruence C tax which quantifies the congruence between two taxonomies, and the
      Relative taxonomic resolving power index R tax which quantifies the potential of
      an approach to capture a high number of species boundaries. The protocols
      differed in the total number of species proposed, between 9 and 34, and were also
      highly incongruent in placing species boundaries. The Generalized Mixed Yule
      Coalescent approach captured the highest number of potential species boundaries
      but many of these were clearly contradicted by extensive nDNA admixture between
      sympatric mitochondrial DNA (mtDNA) haplotype lineages. Delimiting species as
      phenotypically diagnosable mtDNA clades failed to detect two cryptic species that
      are unambiguous due to a lack of nDNA gene flow despite sympatry. We also
      consider the high number of species boundaries and their placement by multi-gene
      Bayesian species delimitation as poorly reliable whereas the Bayesian assignment
      test approach provided a species delimitation highly congruent with integrative
      taxonomic practice. The present study illustrates the trade-off in taxonomy
      between reliability (favored by conservative approaches) and resolving power
      (favored by inflationist approaches). Quantifying excessive splitting is more
      difficult than quantifying excessive lumping, suggesting a priority for
      conservative taxonomies in which errors are more liable to be detected and
      corrected by subsequent studies. 

PMID- 23874562
TI  - Modeling natural photic entrainment in a subterranean rodent (Ctenomys aff.
      knighti), the Tuco-Tuco.
AB  - Subterranean rodents spend most of the day inside underground tunnels, where
      there is little daily change in environmental variables. Our observations of tuco
      tucos (Ctenomys aff. knighti) in a field enclosure indicated that these animals
      perceive the aboveground light-dark cycle by several bouts of light-exposure at
      irregular times during the light hours of the day. To assess whether such light
      dark pattern acts as an entraining agent of the circadian clock, we first
      constructed in laboratory the Phase Response Curve for 1 h light-pulses
      (1000lux). Its shape is qualitatively similar to other curves reported in the
      literature and to our knowledge it is the first Phase Response Curve of a
      subterranean rodent. Computer simulations were performed with a non-linear limit
      cycle oscillator subjected to a simple model of the light regimen experienced by
      tuco-tucos. Results showed that synchronization is achieved even by a simple
      regimen of a single daily light pulse scattered uniformly along the light hours
      of the day. Natural entrainment studies benefit from integrated laboratory, field
      and computational approaches. 

PMID- 23874563
TI  - Distribution of Bartonella henselae variants in patients, reservoir hosts and
      vectors in Spain.
AB  - We have studied the diversity of B. henselae circulating in patients, reservoir
      hosts and vectors in Spain. In total, we have fully characterized 53 clinical
      samples from 46 patients, as well as 78 B. henselae isolates obtained from 35
      cats from La Rioja and Catalonia (northeastern Spain), four positive cat blood
      samples from which no isolates were obtained, and three positive fleas by
      Multiple Locus Sequence Typing and Multiple Locus Variable Number Tandem Repeats
      Analysis. This study represents the largest series of human cases characterized
      with these methods, with 10 different sequence types and 41 MLVA profiles. Two of
      the sequence types and 35 of the profiles were not described previously. Most of
      the B. henselae variants belonged to ST5. Also, we have identified a common
      profile (72) which is well distributed in Spain and was found to persist over
      time. Indeed, this profile seems to be the origin from which most of the variants
      identified in this study have been generated. In addition, ST5, ST6 and ST9 were
      found associated with felines, whereas ST1, ST5 and ST8 were the most frequent
      sequence types found infecting humans. Interestingly, some of the feline
      associated variants never found on patients were located in a separate clade,
      which could represent a group of strains less pathogenic for humans. 

PMID- 23874564
TI  - Differential expression and function of stamp family proteins in adipocyte
      differentiation.
AB  - Six transmembrane protein of prostate (Stamp) proteins play an important role in
      prostate cancer cell growth. Recently, we found that Stamp2 has a critical role
      in the integration of inflammatory and metabolic signals in adipose tissue where
      it is highly expressed and regulated by nutritional and metabolic cues. In this
      study, we show that all Stamp family members are differentially regulated during
      adipogenesis: whereas Stamp1 expression is significantly decreased upon
      differentiation, Stamp2 expression is increased. In contrast, Stamp3 expression
      is modestly changed in adipocytes compared to preadipocytes, and has a biphasic
      expression pattern during the course of differentiation. Suppression of Stamp1 or
      Stamp2 expression both led to inhibition of 3T3-L1 differentiation in concert
      with diminished expression of the key regulators of adipogenesis - CCAAT/enhancer
      binding protein alpha (C/ebpalpha) and peroxisome proliferator-activated receptor
      gamma (Ppargamma). Upon Stamp1 knockdown, mitotic clonal expansion was also
      inhibited. In contrast, Stamp2 knockdown did not affect mitotic clonal expansion,
      but resulted in a marked decrease in superoxide production that is known to
      affect adipogenesis. These results suggest that Stamp1 and Stamp2 play critical
      roles in adipogenesis, but through different mechanisms. 

PMID- 23874565
TI  - Native predators do not influence invasion success of pacific lionfish on
      Caribbean reefs.
AB  - Biotic resistance, the process by which new colonists are excluded from a
      community by predation from and/or competition with resident species, can prevent
      or limit species invasions. We examined whether biotic resistance by native
      predators on Caribbean coral reefs has influenced the invasion success of red
      lionfishes (Pterois volitans and Pterois miles), piscivores from the Indo
      Pacific. Specifically, we surveyed the abundance (density and biomass) of
      lionfish and native predatory fishes that could interact with lionfish (either
      through predation or competition) on 71 reefs in three biogeographic regions of
      the Caribbean. We recorded protection status of the reefs, and abiotic variables
      including depth, habitat type, and wind/wave exposure at each site. We found no
      relationship between the density or biomass of lionfish and that of native
      predators. However, lionfish densities were significantly lower on windward
      sites, potentially because of habitat preferences, and in marine protected areas,
      most likely because of ongoing removal efforts by reserve managers. Our results
      suggest that interactions with native predators do not influence the colonization
      or post-establishment population density of invasive lionfish on Caribbean reefs.

PMID- 23874566
TI  - A superfamily of DNA transposons targeting multicopy small RNA genes.
AB  - Target-specific integration of transposable elements for multicopy genes, such as
      ribosomal RNA and small nuclear RNA (snRNA) genes, is of great interest because
      of the relatively harmless nature, stable inheritance and possible application
      for targeted gene delivery of target-specific transposable elements. To date,
      such strict target specificity has been observed only among non-LTR
      retrotransposons. We here report a new superfamily of sequence-specific DNA
      transposons, designated Dada. Dada encodes a DDE-type transposase that shows a
      distant similarity to transposases encoded by eukaryotic MuDR, hAT, P and Kolobok
      transposons, as well as the prokaryotic IS256 insertion element. Dada generates 6
      7 bp target site duplications upon insertion. One family of Dada DNA transposons
      targets a specific site inside the U6 snRNA genes and are found in various fish
      species, water flea, oyster and polycheate worm. Other target sequences of the
      Dada transposons are U1 snRNA genes and different tRNA genes. The targets are
      well conserved in multicopy genes, indicating that copy number and sequence
      conservation are the primary constraints on the target choice of Dada
      transposons. Dada also opens a new frontier for target-specific gene delivery
      application. 

PMID- 23874567
TI  - Decoding speech perception by native and non-native speakers using single-trial
      electrophysiological data.
AB  - Brain-computer interfaces (BCIs) are systems that use real-time analysis of
      neuroimaging data to determine the mental state of their user for purposes such
      as providing neurofeedback. Here, we investigate the feasibility of a BCI based
      on speech perception. Multivariate pattern classification methods were applied to
      single-trial EEG data collected during speech perception by native and non-native
      speakers. Two principal questions were asked: 1) Can differences in the perceived
      categories of pairs of phonemes be decoded at the single-trial level? 2) Can
      these same categorical differences be decoded across participants, within or
      between native-language groups? Results indicated that classification performance
      progressively increased with respect to the categorical status (within, boundary
      or across) of the stimulus contrast, and was also influenced by the native
      language of individual participants. Classifier performance showed strong
      relationships with traditional event-related potential measures and behavioral
      responses. The results of the cross-participant analysis indicated an overall
      increase in average classifier performance when trained on data from all
      participants (native and non-native). A second cross-participant classifier
      trained only on data from native speakers led to an overall improvement in
      performance for native speakers, but a reduction in performance for non-native
      speakers. We also found that the native language of a given participant could be
      decoded on the basis of EEG data with accuracy above 80%. These results indicate
      that electrophysiological responses underlying speech perception can be decoded
      at the single-trial level, and that decoding performance systematically reflects
      graded changes in the responses related to the phonological status of the
      stimuli. This approach could be used in extensions of the BCI paradigm to support
      perceptual learning during second language acquisition. 

PMID- 23874568
TI  - Lignin depletion enhances the digestibility of cellulose in cultured xylem cells.
AB  - Plant lignocellulose constitutes an abundant and sustainable source of
      polysaccharides that can be converted into biofuels. However, the enzymatic
      digestion of native plant cell walls is inefficient, presenting a considerable
      barrier to cost-effective biofuel production. In addition to the insolubility of
      cellulose and hemicellulose, the tight association of lignin with these
      polysaccharides intensifies the problem of cell wall recalcitrance. To determine
      the extent to which lignin influences the enzymatic digestion of cellulose,
      specifically in secondary walls that contain the majority of cellulose and lignin
      in plants, we used a model system consisting of cultured xylem cells from
      Zinniaelegans. Rather than using purified cell wall substrates or plant tissue,
      we have applied this system to study cell wall degradation because it
      predominantly consists of homogeneous populations of single cells exhibiting
      large deposits of lignocellulose. We depleted lignin in these cells by treating
      with an oxidative chemical or by inhibiting lignin biosynthesis, and then
      examined the resulting cellulose digestibility and accessibility using a
      fluorescent cellulose-binding probe. Following cellulase digestion, we measured a
      significant decrease in relative cellulose content in lignin-depleted cells,
      whereas cells with intact lignin remained essentially unaltered. We also observed
      a significant increase in probe binding after lignin depletion, indicating that
      decreased lignin levels improve cellulose accessibility. These results indicate
      that lignin depletion considerably enhances the digestibility of cellulose in the
      cell wall by increasing the susceptibility of cellulose to enzymatic attack.
      Although other wall components are likely to contribute, our quantitative study
      exploits cultured Zinnia xylem cells to demonstrate the dominant influence of
      lignin on the enzymatic digestion of the cell wall. This system is simple enough
      for quantitative image analysis, but realistic enough to capture the natural
      complexity of lignocellulose in the plant cell wall. Consequently, these cells
      represent a suitable model for analyzing native lignocellulose degradation. 

PMID- 23874570
TI  - Mapping cortical degeneration in ALS with magnetization transfer ratio and voxel
      based morphometry.
AB  - Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS)
      is a multisystem disease involving several cerebral cortical areas. Advanced
      quantitative magnetic resonance imaging (MRI) techniques enable to explore in
      vivo the volume and microstructure of the cerebral cortex in ALS. We studied with
      a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging
      approach the capability of MRI to identify the cortical areas affected by
      neurodegeneration in ALS patients. Eighteen ALS patients and 18 age-matched
      healthy controls were examined on a 1.5T scanner using a high-resolution 3D T1
      weighted spoiled gradient recalled sequence with and without MT saturation pulse.
      A voxel-based analysis (VBA) was adopted in order to automatically compute the
      regional atrophy and MT ratio (MTr) changes of the entire cerebral cortex. By
      using a multimodal image analysis MTr was adjusted for local gray matter (GM)
      atrophy to investigate if MTr changes can be independent of atrophy of the
      cerebral cortex. VBA revealed several clusters of combined GM atrophy and MTr
      decrease in motor-related areas and extra-motor frontotemporal cortex. The
      multimodal image analysis identified areas of isolated MTr decrease in premotor
      and extra-motor frontotemporal areas. VBM and MTr are capable to detect the
      distribution of neurodegenerative alterations in the cortical GM of ALS patients,
      supporting the hypothesis of a multi-systemic involvement in ALS. MT imaging
      changes exist beyond volume loss in frontotemporal cortices. 

PMID- 23874571
TI  - Silicon dioxide thin film mediated single cell nucleic acid isolation.
AB  - A limited amount of DNA extracted from single cells, and the development of
      single cell diagnostics make it necessary to create a new highly effective method
      for the single cells nucleic acids isolation. In this paper, we propose the DNA
      isolation method from biomaterials with limited DNA quantity in sample, and from
      samples with degradable DNA based on the use of solid-phase adsorbent silicon
      dioxide nanofilm deposited on the inner surface of PCR tube. 

PMID- 23874572
TI  - Pharmacometabolomics of response to sertraline and to placebo in major depressive
      disorder - possible role for methoxyindole pathway.
AB  - Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major
      Depressive Disorder (MDD) varies considerably among patients, and the onset of
      antidepressant therapeutic action is delayed until after 2 to 4 weeks of
      treatment. The objective of this study was to analyze changes within
      methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine
      whether differential regulation within these branches may contribute to mechanism
      of variation in response to treatment. Metabolomics approach was used to
      characterize early biochemical changes in tryptophan pathway and correlated
      biochemical changes with treatment outcome. Outpatients with MDD were randomly
      assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week
      trial; response to treatment was measured using the 17-item Hamilton Rating Scale
      for Depression (HAMD17). Targeted electrochemistry based metabolomic platform
      (LCECA) was used to profile serum samples from MDD patients. The response rate
      was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%],
      respectively, chi(2)(1)  = 0.75, p = 0.39). Patients showing a good response to
      sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM),
      greater reduction in 5-MTPM levels after treatment, an increase in 5
      Methoxytryptophol (5-MTPOL) and Melatonin (MEL) levels, and decreases in the
      (KYN)/MEL and 3-Hydroxykynurenine (3-OHKY)/MEL ratios post-treatment compared to
      pretreatment. These changes were not seen in the patients showing poor response
      to sertraline. In the placebo group, more favorable treatment outcome was
      associated with increases in 5-MTPOL and MEL levels and significant decreases in
      the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the
      4-week response. These results suggest that recovery from a depressed state due
      to treatment with drug or with placebo could be associated with preferential
      utilization of serotonin for production of melatonin and 5-MTPOL. 

PMID- 23874573
TI  - Personality and dietary intake - findings in the Helsinki birth cohort study.
AB  - BACKGROUND: Personality traits are associated with health outcomes including non
      communicable diseases. This could be partly explained by lifestyle related
      factors including diet. The personality traits neuroticism, extraversion,
      openness, agreeableness, and conscientiousness are linked with resilience,
      meaning adaptability in challenging situations. Resilient people usually comply
      with favorable health behaviors. OBJECTIVE: Our objective was to explore the
      associations between food and nutrient intake, personality traits and resilience.
      DESIGN: A validated semi-quantitative food frequency questionnaire was used to
      measure diet and the NEO-personality inventory to assess personality in 1681
      subjects. Linear regression analysis was used to explore diet-personality
      associations and cluster analysis to define resilient and non-resilient
      personality profiles. RESULTS: Adjusting for age, education and energy intake,
      and applying Bonferroni corrections, openness in men was associated with higher
      vegetable (14.9 g/d for 1 SD increase in the personality score, PBonf <0.01) and
      lower confectionery and chocolate (-2.8 g/d, PBonf <0.01) intakes. In women,
      neuroticism was associated with lower fish (-4.9 g/d, PBonf <0.001) and vegetable
      (-18.9 g/d, PBonf <0.01) and higher soft drink (19.9 g/d, PBonf <0.001) intakes.
      Extraversion, in women, associated with higher meat (5.9 g/d, PBonf <0.05) and
      vegetable (24.8 g/d, PBonf <0.001) intakes, openness with higher vegetable (23.4
      g/d, PBonf <0.001) and fruit (29.5 g/d, PBonf <0.01) intakes. Agreeableness was
      associated with a lower soft drink (-16.2 g/d, PBonf <0.01) and conscientiousness
      with a higher fruit (32.9 g/d, PBonf<0.01) intake in women. Comparing resilient
      and non-resilient subjects, we found resilience in women to be associated with
      higher intakes of vegetables (52.0 g/d, P<0.001), fruits (58.3 g/d, P<0.01), fish
      (8.6 g/d, P<0.01) and dietary fiber (1.6 g/d, P<0.01). CONCLUSION: Personality
      traits are associated with dietary intake and especially subjects with resilient
      personality profiles had healthier dietary intakes. These associations were
      stronger in women than in men.

PMID- 23874574
TI  - Corruption of the intra-gene DNA methylation architecture is a hallmark of
      cancer.
AB  - Epigenetic processes--including DNA methylation--are increasingly seen as having
      a fundamental role in chronic diseases like cancer. It is well known that
      methylation levels at particular genes or loci differ between normal and diseased
      tissue. Here we investigate whether the intra-gene methylation architecture is
      corrupted in cancer and whether the variability of levels of methylation of
      individual CpGs within a defined gene is able to discriminate cancerous from
      normal tissue, and is associated with heterogeneous tumour phenotype, as defined
      by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284
      cancerous and 681 normal samples, corresponding to 14 different cancer types. In
      doing so, we found novel differences in intra-gene methylation pattern across
      phenotypes, particularly in those genes which are crucial for stem cell biology;
      our measures of intra-gene methylation architecture are a better determinant of
      phenotype than measures based on mean methylation level alone (K-S test [Formula:
      see text] in all 14 diseases tested). These per-gene methylation measures also
      represent a considerable reduction in complexity, compared to conventional per
      CpG beta-values. Our findings strongly support the view that intra-gene
      methylation architecture has great clinical potential for the development of DNA
      based cancer biomarkers.

PMID- 23874575
TI  - Directly administered antiretroviral therapy for HIV-infected individuals in
      opioid treatment programs: results from a randomized clinical trial.
AB  - BACKGROUND: Data regarding the efficacy of directly administered antiretroviral
      therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient
      framework for DAART. In a randomized controlled trial, we compared DAART and self
      administered therapy (SAT) among HIV-infected subjects attending five OTPs in
      Baltimore, MD. METHODS: HIV-infected individuals attending OTPs were eligible if
      they were not taking antiretroviral therapy (ART) or were virologically failing
      ART at last clinical assessment. In subjects assigned to DAART, we observed one
      ART dose per weekday at the OTP for up to 12 months. SAT subjects administered
      ART at home. The primary efficacy comparison was the between-arm difference in
      the average proportions with HIV RNA <50 copies/mL during the intervention phase
      (3-, 6-, and 12-month study visits), using a logistic regression model accounting
      for intra-person correlation due to repeated observations. Adherence was measured
      with electronic monitors in both arms. RESULTS: We randomized 55 and 52 subjects
      from five Baltimore OTPs to DAART and SAT, respectively. The average proportions
      with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and
      0.40 in SAT (difference 0.11, 95% CI: -0.020 to 0.24). There were no significant
      differences between arms in electronically-measured adherence, average CD4 cell
      increase from baseline, average change in log10 HIV RNA from baseline,
      opportunistic conditions, hospitalizations, mortality, or the development of new
      drug resistance mutations. CONCLUSIONS: In this randomized trial, we found little
      evidence that DAART provided clinical benefits compared to SAT among HIV-infected
      subjects attending OTPs. TRIAL REGISTRATION: ClinicalTrials.gov NCT00279110
      NCT00279110&quest;term&hairsp;&equals;&hairsp;NCT00279110&rank&hairsp;&equals;&ha
      rsp;1.

PMID- 23874576
TI  - Gene set based integrated data analysis reveals phenotypic differences in a brain
      cancer model.
AB  - A key challenge in the data analysis of biological high-throughput experiments is
      to handle the often low number of samples in the experiments compared to the
      number of biomolecules that are simultaneously measured. Combining experimental
      data using independent technologies to illuminate the same biological trends, as
      well as complementing each other in a larger perspective, is one natural way to
      overcome this challenge. In this work we investigated if integrating proteomics
      and transcriptomics data from a brain cancer animal model using gene set based
      analysis methodology, could enhance the biological interpretation of the data
      relative to more traditional analysis of the two datasets individually. The brain
      cancer model used is based on serial passaging of transplanted human brain tumor
      material (glioblastoma--GBM) through several generations in rats. These serial
      transplantations lead over time to genotypic and phenotypic changes in the tumors
      and represent a medically relevant model with a rare access to samples and where
      consequent analyses of individual datasets have revealed relatively few
      significant findings on their own. We found that the integrated analysis both
      performed better in terms of significance measure of its findings compared to
      individual analyses, as well as providing independent verification of the
      individual results. Thus a better context for overall biological interpretation
      of the data can be achieved.

PMID- 23874569
TI  - Ectomycorrhizal-dominated boreal and tropical forests have distinct fungal
      communities, but analogous spatial patterns across soil horizons.
AB  - Fungi regulate key nutrient cycling processes in many forest ecosystems, but
      their diversity and distribution within and across ecosystems are poorly
      understood. Here, we examine the spatial distribution of fungi across a boreal
      and tropical ecosystem, focusing on ectomycorrhizal fungi. We analyzed fungal
      community composition across litter (organic horizons) and underlying soil
      horizons (0-20 cm) using 454 pyrosequencing and clone library sequencing. In both
      forests, we found significant clustering of fungal communities by site and soil
      horizons with analogous patterns detected by both sequencing technologies. Free
      living saprotrophic fungi dominated the recently-shed leaf litter and
      ectomycorrhizal fungi dominated the underlying soil horizons. This vertical
      pattern of fungal segregation has also been found in temperate and European
      boreal forests, suggesting that these results apply broadly to ectomycorrhizal
      dominated systems, including tropical rain forests. Since ectomycorrhizal and
      free-living saprotrophic fungi have different influences on soil carbon and
      nitrogen dynamics, information on the spatial distribution of these functional
      groups will improve our understanding of forest nutrient cycling. 

PMID- 23874577
TI  - Effect of lifestyle on asthma control in Japanese patients: importance of
      periodical exercise and raw vegetable diet.
AB  - BACKGROUND: The avoidance of inhaled allergens or tobacco smoke has been known to
      have favorable effects on asthma control. However, it remains unclear whether
      other lifestyle-related factors are also related to asthma control. Therefore, a
      comprehensive study to examine the associations between various lifestyle factors
      and asthma control was conducted in Japanese asthmatic patients. METHODS: The
      study subjects included 437 stable asthmatic patients recruited from our
      outpatient clinic over a one-year period. A written, informed consent was
      obtained from each participant. Asthma control was assessed using the asthma
      control test (ACT), and a structured questionnaire was administered to obtain
      information regarding lifestyle factors, including tobacco smoking, alcohol
      drinking, physical exercise, and diet. Both bivariate and multivariate analyses
      were conducted. RESULTS: The proportions of total control (ACT = 25), well
      controlled (ACT = 20-24), and poorly controlled (ACT < 20) were 27.5%, 48.1%, and
      24.5%, respectively. The proportions of patients in the asthma treatment steps as
      measured by Global Initiative for Asthma 2007 in step 1, step 2, step 3, step 4,
      and step 5 were 5.5%, 17.4%, 7.6%, 60.2%, and 9.4%, respectively. Body mass
      index, direct tobacco smoking status and alcohol drinking were not associated
      with asthma control. On the other hand, younger age (< 65 years old), passive
      smoking, periodical exercise (> 3 metabolic equivalents-h/week), and raw
      vegetable intake (> 5 units/week) were significantly associated with good asthma
      control by bivariate analysis. Younger age, periodical exercise, and raw
      vegetable intake were significantly associated with good asthma control by
      multiple linear regression analysis. CONCLUSIONS: Periodical exercise and raw
      vegetable intake are associated with good asthma control in Japanese patients.

PMID- 23874578
TI  - Cancer stem cell-like side population cells in clear cell renal cell carcinoma
      cell line 769P.
AB  - Although cancers are widely considered to be maintained by stem cells, the
      existence of stem cells in renal cell carcinoma (RCC) has seldom been reported,
      in part due to the lack of unique surface markers. We here identified cancer stem
      cell-like cells with side population (SP) phenotype in five human RCC cell lines.
      Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line,
      contained the largest amount of SP cells as compared with other four cell lines.
      These 769P SP cells possessed characteristics of proliferation, self-renewal, and
      differentiation, as well as strong resistance to chemotherapy and radiotherapy
      that were possibly related to the ABCB1 transporter. In vivo experiments with
      serial tumor transplantation in mice also showed that 769P SP cells formed tumors
      in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have
      the properties of cancer stem cells, which may play important roles in
      tumorigenesis and therapy-resistance of RCC. 

PMID- 23874579
TI  - Renal cells express different forms of vimentin: the independent expression
      alteration of these forms is important in cell resistance to osmotic stress and
      apoptosis.
AB  - Osmotic stress has been shown to regulate cytoskeletal protein expression. It is
      generally known that vimentin is rapidly degraded during apoptosis by multiple
      caspases, resulting in diverse vimentin fragments. Despite the existence of the
      known apoptotic vimentin fragments, we demonstrated in our study the existence of
      different forms of vimentin VIM I, II, III, and IV with different molecular
      weights in various renal cell lines. Using a proteomics approach followed by
      western blot analyses and immunofluorescence staining, we proved the apoptosis
      independent existence and differential regulation of different vimentin forms
      under varying conditions of osmolarity in renal cells. Similar impacts of osmotic
      stress were also observed on the expression of other cytoskeleton intermediate
      filament proteins; e.g., cytokeratin. Interestingly, 2D western blot analysis
      revealed that the forms of vimentin are regulated independently of each other
      under glucose and NaCl osmotic stress. Renal cells, adapted to high NaCl osmotic
      stress, express a high level of VIM IV (the form with the highest molecular
      weight), besides the three other forms, and exhibit higher resistance to
      apoptotic induction with TNF-alpha or staurosporin compared to the control. In
      contrast, renal cells that are adapted to high glucose concentration and express
      only the lower-molecular-weight forms VIM I and II, were more susceptible to
      apoptosis. Our data proved the existence of different vimentin forms, which play
      an important role in cell resistance to osmotic stress and are involved in cell
      protection against apoptosis.

PMID- 23874580
TI  - Analysis of the airway microbiota of healthy individuals and patients with
      chronic obstructive pulmonary disease by T-RFLP and clone sequencing.
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory lung
      disease that affects a large number of patients and has significant impact. One
      hallmark of the disease is the presence of bacteria in the lower airways.
      OBJECTIVE: The aim of this study was to analyze the detailed structure of
      microbial communities found in the lungs of healthy individuals and patients with
      COPD. Nine COPD patients as compared and 9 healthy individuals underwent flexible
      bronchoscopy and BAL was performed. Bacterial nucleic acids were subjected to
      terminal restriction fragment (TRF) length polymorphism and clone library
      analysis. Overall, we identified 326 T-RFLP band, 159 in patients and 167 in
      healthy controls. The results of the TRF analysis correlated partly with the data
      obtained from clone sequencing. Although the results of the sequencing showed
      high diversity, the genera Prevotella, Sphingomonas, Pseudomonas, Acinetobacter,
      Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus
      constituted the major part of the core microbiome found in both groups. A TRF
      band possibly representing Pseudomonas sp. monoinfection was associated with a
      reduction of the microbial diversity. Non-cultural methods reveal the complexity
      of the pulmonary microbiome in healthy individuals and in patients with COPD.
      Alterations of the microbiome in pulmonary diseases are correlated with disease.

PMID- 23874581
TI  - Mesothelin virus-like particle immunization controls pancreatic cancer growth
      through CD8+ T cell induction and reduction in the frequency of CD4+ foxp3+ ICOS-
      regulatory T cells.
AB  - Our previous study has shown that mesothelin (MSLN) is a potential
      immunotherapeutic target for pancreatic cancer. Here, we further studied the
      immunogenicity of chimeric murine MSLN-virus-like particles (mMSLN-VLPs), their
      ability to break tolerance to mMSLN, a self-antigen, and deciphered the mechanism
      of immune responses elicited by mMSLN-VLP immunization using a pancreatic cancer
      (PC) mouse model. In addition to what we have found with xenogeneic human MSLN
      VLP (hMSLN-VLP), mMSLN-VLP immunization was able to break the tolerance to
      intrinsic MSLN and mount mMSLN-specific, cytotoxic CD8(+) T cells which led to a
      significant reduction in tumor volume and prolonged survival in an orthotopic PC
      mouse model. Furthermore, CD4(+)foxp3(+) regulatory T cells (Tregs) were
      progressively decreased in both spleen and tumor tissues following mMSLN-VLP
      immunization and this was at least partly due to elevated levels of IL-6
      production from activated plasmocytoid dendritic cell (pDC)-like cells following
      mMSLN-VLP immunization. Moreover, mMSLN-VLP treatment mainly reduced the
      frequency of the CD4(+)foxp3(+)ICOS(-) Treg subset. However, mMSLN-VLP induced IL
      6 production also increased ICOSL expression on pDC-like cells which supported
      the proliferation of immunosuppressive CD4(+)foxp3(+)ICOS(+) Treg cells. This
      study reveals that mMSLN-VLP immunization is capable of controlling PC
      progression by effectively mounting an immune response against mMSLN, a tumor
      self-antigen, and altering the immunosuppressive tumor microenvironment via
      activation of pDCs-like cells and reduction in the frequency of
      CD4(+)foxp3(+)ICOS(-) Treg cells. However, combination therapies will likely need
      to be used in order to target residual CD4(+)foxp3(+)ICOS(+) Treg cells. 

PMID- 23874582
TI  - Slow sedimentation and deformability of charged lipid vesicles.
AB  - The study of vesicles in suspension is important to understand the complicated
      dynamics exhibited by cells in in vivo and in vitro. We developed a computer
      simulation based on the boundary-integral method to model the three dimensional
      gravity-driven sedimentation of charged vesicles towards a flat surface. The
      membrane mechanical behavior was modeled using the Helfrich Hamiltonian and near
      incompressibility of the membrane was enforced via a model which accounts for the
      thermal fluctuations of the membrane. The simulations were verified and compared
      to experimental data obtained using suspended vesicles labelled with a
      fluorescent probe, which allows visualization using fluorescence microscopy and
      confers the membrane with a negative surface charge. The electrostatic
      interaction between the vesicle and the surface was modeled using the linear
      Derjaguin approximation for a low ionic concentration solution. The sedimentation
      rate as a function of the distance of the vesicle to the surface was determined
      both experimentally and from the computer simulations. The gap between the
      vesicle and the surface, as well as the shape of the vesicle at equilibrium were
      also studied. It was determined that inclusion of the electrostatic interaction
      is fundamental to accurately predict the sedimentation rate as the vesicle
      approaches the surface and the size of the gap at equilibrium, we also observed
      that the presence of charge in the membrane increases its rigidity. 

PMID- 23874583
TI  - Changes in benthos associated with mussel (Mytilus edulis L.) farms on the west
      coast of Scotland.
AB  - Aquaculture, as a means of food production, is growing rapidly in response to an
      increasing demand for protein and the over-exploitation of wild fisheries. This
      expansion includes mussels (family Mytilidae) where production currently stands
      at 1.5 million tonnes per annum. Mussel culture is frequently perceived as having
      little environmental impact yet mussel biodeposits and shell debris accumulate
      around the production site and are linked to changes in the benthos. To assess
      the extent and nature of changes in benthos associated with mussel farming grab
      and video sampling around seven mussel farms was conducted. Grab samples were
      analysed for macrofauna and shell-hash content whilst starfish were counted and
      the shell-hash cover estimated from video imaging. Shell-hash was patchily
      distributed and occasionally dominated sediments (maximum of 2116 g per 0.1 m(2)
      grab). Mean shell-hash content decreased rapidly at distances >5 m from the line
      and, over the distance 1-64 m, decreased by three orders of magnitude. The
      presence of shell-hash and the distance-from-line influenced macrofaunal
      assemblages but this effect differed between sites. There was no evidence that
      mussel farming was associated with changes in macrobenthic diversity, species
      count or feeding strategy. However, total macrofaunal count was estimated to be
      2.5 times higher in close proximity to the lines, compared with 64 m distance,
      and there was evidence that this effect was conditional on the presence of shell
      hash. Starfish density varied considerably between sites but, overall, they were
      approximately 10 times as abundant close to the mussel-lines compared with 64 m
      distance. There was no evidence that starfish were more abundant in the presence
      of shell-hash visible on the sediment surface. In terms of farm-scale benthic
      impacts these data suggest that mussel farming is a relatively benign way of
      producing food, compared with intensive fish-farming, in similar environments. 

PMID- 23874585
TI  - Child deaths due to injury in the four UK countries: a time trends study from
      1980 to 2010.
AB  - BACKGROUND: Injuries are an increasingly important cause of death in children
      worldwide, yet injury mortality is highly preventable. Determining patterns and
      trends in child injury mortality can identify groups at particularly high risk.
      We compare trends in child deaths due to injury in four UK countries, between
      1980 and 2010. METHODS: We obtained information from death certificates on all
      deaths occurring between 1980 and 2010 in children aged 28 days to 18 years and
      resident in England, Scotland, Wales or Northern Ireland. Injury deaths were
      defined by an external cause code recorded as the underlying cause of death.
      Injury mortality rates were analysed by type of injury, country of residence, age
      group, sex and time period. RESULTS: Child mortality due to injury has declined
      in all countries of the UK. England consistently experienced the lowest mortality
      rate throughout the study period. For children aged 10 to 18 years, differences
      between countries in mortality rates increased during the study period. Inter
      country differences were largest for boys aged 10 to 18 years with mortality rate
      ratios of 1.38 (95% confidence interval 1.16, 1.64) for Wales, 1.68 (1.48, 1.91)
      for Scotland and 1.81 (1.50, 2.18) for Northern Ireland compared with England
      (the baseline) in 2006-10. The decline in mortality due to injury was accounted
      for by a decline in unintentional injuries. For older children, no declines were
      observed for deaths caused by self-harm, by assault or from undetermined intent
      in any UK country. CONCLUSION: Whilst child deaths from injury have declined in
      all four UK countries, substantial differences in mortality rates remain between
      countries, particularly for older boys. This group stands to gain most from
      policy interventions to reduce deaths from injury in children.

PMID- 23874584
TI  - Altered protein networks and cellular pathways in severe west nile disease in
      mice.
AB  - BACKGROUND: The recent West Nile virus (WNV) outbreaks in developed countries,
      including Europe and the United States, have been associated with significantly
      higher neuropathology incidence and mortality rate than previously documented.
      The changing epidemiology, the constant risk of (re-)emergence of more virulent
      WNV strains, and the lack of effective human antiviral therapy or vaccines makes
      understanding the pathogenesis of severe disease a priority. Thus, to gain
      insight into the pathophysiological processes in severe WNV infection, a kinetic
      analysis of protein expression profiles in the brain of WNV-infected mice was
      conducted using samples prior to and after the onset of clinical symptoms.
      METHODOLOGY/PRINCIPAL FINDINGS: To this end, 2D-DIGE and gel-free iTRAQ labeling
      approaches were combined, followed by protein identification by mass
      spectrometry. Using these quantitative proteomic approaches, a set of 148
      proteins with modified abundance was identified. The bioinformatics analysis
      (Ingenuity Pathway Analysis) of each protein dataset originating from the
      different time-point comparisons revealed that four major functions were altered
      during the course of WNV-infection in mouse brain tissue: i) modification of
      cytoskeleton maintenance associated with virus circulation; ii) deregulation of
      the protein ubiquitination pathway; iii) modulation of the inflammatory response;
      and iv) alteration of neurological development and neuronal cell death. The
      differential regulation of selected host protein candidates as being
      representative of these biological processes were validated by western blotting
      using an original fluorescence-based method. CONCLUSION/SIGNIFICANCE: This study
      provides novel insights into the in vivo kinetic host reactions against WNV
      infection and the pathophysiologic processes involved, according to clinical
      symptoms. This work offers useful clues for anti-viral research and further
      evaluation of early biomarkers for the diagnosis and prevention of severe
      neurological disease caused by WNV.

PMID- 23874586
TI  - Phase II study of concurrent capecitabine and external beam radiotherapy for pain
      control of bone metastases of breast cancer origin.
AB  - BACKGROUND: Pain from bone metastases of breast cancer origin is treated with
      localized radiation. Modulating doses and schedules has shown little efficacy in
      improving results. Given the synergistic therapeutic effect reported for combined
      systemic chemotherapy with local radiation in anal, rectal, and head and neck
      malignancies, we sought to evaluate the tolerability and efficacy of combined
      capecitabine and radiation for palliation of pain due to bone metastases from
      breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-nine women with painful
      bone metastases from breast cancer were treated with external beam radiation in
      10 fractions of 3 Gy, 5 fractions a week for 2 consecutive weeks. Oral
      capecitabine 700 mg/m(2) twice daily was administered throughout radiation
      therapy. Rates of complete response, defined as a score of 0 on a 10-point pain
      scale and no increase in analgesic consumption, were 14% at 1 week, 38% at 2
      weeks, 52% at 4 weeks, 52% at 8 weeks, and 48% at 12 weeks. Corresponding rates
      of partial response, defined as a reduction of at least 2 points in pain score
      without an increase in analgesics consumption, were 31%, 38%, 28%, 34% and 38%.
      The overall response rate (complete and partial) at 12 weeks was 86%. Side
      effects were of mild intensity (grade I or II) and included nausea (38% of
      patients), weakness (24%), diarrhea (24%), mucositis (10%), and hand and foot
      syndrome (7%). CONCLUSIONS/SIGNIFICANCE: External beam radiation with concurrent
      capecitabine is safe and tolerable for the treatment of pain from bone metastases
      of breast cancer origin. The overall and complete response rates in our study are
      unusually high compared to those reported for radiation alone. Further evaluation
      of this approach, in a randomized study, is warranted. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01784393NCT01784393.

PMID- 23874587
TI  - Spatial distribution of podoconiosis in relation to environmental factors in
      Ethiopia: a historical review.
AB  - BACKGROUND: An up-to-date and reliable map of podoconiosis is needed to design
      geographically targeted and cost-effective intervention in Ethiopia. Identifying
      the ecological correlates of the distribution of podoconiosis is the first step
      for distribution and risk maps. The objective of this study was to investigate
      the spatial distribution and ecological correlates of podoconiosis using
      historical and contemporary survey data. METHODS: Data on the observed prevalence
      of podoconiosis were abstracted from published and unpublished literature into a
      standardized database, according to strict inclusion and exclusion criteria. In
      total, 10 studies conducted between 1969 and 2012 were included, and data were
      available for 401,674 individuals older than 15 years of age from 229 locations.
      A range of high resolution environmental factors were investigated to determine
      their association with podoconiosis prevalence, using logistic regression.
      RESULTS: The prevalence of podoconiosis in Ethiopia was estimated at 3.4% (95% CI
      3.3%-3.4%) with marked regional variation. We identified significant associations
      between mean annual Land Surface Temperature (LST), mean annual precipitation,
      topography of the land and fine soil texture and high prevalence of podoconiosis.
      The derived maps indicate both widespread occurrence of podoconiosis and a marked
      variability in prevalence of podoconiosis, with prevalence typically highest at
      altitudes >1500 m above sea level (masl), with >1500 mm annual rainfall and mean
      annual LST of 19-21 degrees C. No (or very little) podoconiosis occurred at
      altitudes <1225 masl, with annual rainfall <900 mm, and mean annual LST of >24
      degrees C. CONCLUSION: Podoconiosis remains a public health problem in Ethiopia
      over considerable areas of the country, but exhibits marked geographical
      variation associated in part with key environmental factors. This is work in
      progress and the results presented here will be refined in future work.

PMID- 23874588
TI  - Short-term soy isoflavone intervention in patients with localized prostate
      cancer: a randomized, double-blind, placebo-controlled trial.
AB  - PURPOSE: We describe the effects of soy isoflavone consumption on prostate
      specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men
      with localized prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a
      double-blinded, randomized, placebo-controlled trial to examine the effect of soy
      isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units) on
      serum and tissue biomarkers in patients with localized prostate cancer. Eighty
      six men were randomized to treatment with isoflavones (n=42) or placebo (n=44)
      for up to six weeks prior to scheduled prostatectomy. We performed microarray
      analysis using a targeted cell cycle regulation and apoptosis gene chip
      (GEArrayTM). Changes in serum total testosterone, free testosterone, total
      estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid
      point, and at the time of radical prostatectomy. In this preliminary analysis, 12
      genes involved in cell cycle control and 9 genes involved in apoptosis were down
      regulated in the treatment tumor tissues versus the placebo control. Changes in
      serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and
      total cholesterol in the isoflavone-treated group compared to men receiving
      placebo were not statistically significant. CONCLUSIONS/SIGNIFICANCE: These data
      suggest that short-term intake of soy isoflavones did not affect serum hormone
      levels, total cholesterol, or PSA. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00255125.

PMID- 23874589
TI  - Antidiabetic, antihyperlipidemic and antioxidant activities of a novel
      proteoglycan from ganoderma lucidum fruiting bodies on db/db mice and the
      possible mechanism.
AB  - Previously, we screened a proteoglycan for anti-hyperglycemic, named FYGL, from
      Ganoderma Lucidum. For further research of the antidiabetic mechanisms of FYGL in
      vivo, the glucose homeostasis, activities of insulin-sensitive enzymes, glucose
      transporter expression and pancreatic function were analyzed using db/db mice as
      diabetic models in the present work. FYGL not only lead to a reduction in
      glycated hemoglobin level, but also an increase in insulin and C-peptide level,
      whereas a decrease in glucagons level and showed a potential for the remediation
      of pancreatic islets. FYGL also increased the glucokinase activities, and
      simultaneously lowered the phosphoenol pyruvate carboxykinase activities,
      accompanied by a reduction in the expression of hepatic glucose transporter
      protein 2, while the expression of adipose and skeletal glucose transporter
      protein 4 was increased. Moreover, the antioxidant enzyme activities were also
      increased by FYGL treatment. Thus, FYGL was an effective antidiabetic agent by
      enhancing insulin secretion and decreasing hepatic glucose output along with
      increase of adipose and skeletal muscle glucose disposal in the late stage of
      diabetes. Furthermore, FYGL is beneficial against oxidative stress, thereby being
      helpful in preventing the diabetic complications. 

PMID- 23874590
TI  - Synergistic antitumor effect between gefitinib and fractionated irradiation in
      anaplastic oligodendrogliomas cannot be predicted by the Egfr signaling activity.
AB  - In high-grade gliomas, the identification of patients that could benefit from
      EGFR inhibitors remains a challenge, hindering the use of these agents. Using
      xenografts models, we evaluated the antitumor effect of the combined treatment
      "gefitinib + radiotherapy" and aimed to identify the profile of responsive
      tumors. Expression of phosphorylated proteins involved in the EGFR-dependent
      signaling pathways was analyzed in 10 glioma models. We focused on three models
      of anaplastic oligodendrogliomas (TCG2, TCG3 and TCG4) harboring high levels of
      phospho-EGFR, phospho-AKT and phospho-MEK1. They were treated with gefitinib (GEF
      75 mg/kg/day x 5 days/week, for 2 weeks) and/or fractionated radiotherapy (RT:
      5x2Gy/week for 2 weeks). Our results showed that GEF and/or RT induced
      significant tumor growth delays. However, only the TCG3 xenografts were highly
      responsive to the combination GEF+RT, with ~50% of tumor cure. Phosphoproteins
      analysis five days after treatment onset demonstrated in TCG3 xenografts, but not
      in TCG2 model, that the EGFR-dependent pathways were inhibited after GEF
      treatment. Moreover, TCG3-bearing mice receiving GEF monotherapy exhibited a
      transient beneficial therapeutic response, rapidly followed by tumor regrowth,
      along with a major vascular remodeling. Taken together, our data evoked an "EGFR
      addictive" behavior for TCG3 tumors. This study confirms that combination of
      gefitinib with fractionated irradiation could be a potent therapeutic strategy
      for anaplastic oligodendrogliomas harboring EGFR abnormalities but this treatment
      seems mainly beneficial for "EGFR-addictive" tumors. Unfortunately, neither the
      usual molecular markers (EGFR amplification, PTEN loss) nor the basal
      overexpression of phosphoproteins were useful to distinguish this responsive
      tumor. Evaluating the impact of TKIs on the EGFR-dependent pathways during the
      treatment might be more relevant, and requires further validation. 

PMID- 23874592
TI  - New approaches for calculating Moran's index of spatial autocorrelation.
AB  - Spatial autocorrelation plays an important role in geographical analysis;
      however, there is still room for improvement of this method. The formula for
      Moran's index is complicated, and several basic problems remain to be solved.
      Therefore, I will reconstruct its mathematical framework using mathematical
      derivation based on linear algebra and present four simple approaches to
      calculating Moran's index. Moran's scatterplot will be ameliorated, and new test
      methods will be proposed. The relationship between the global Moran's index and
      Geary's coefficient will be discussed from two different vantage points: spatial
      population and spatial sample. The sphere of applications for both Moran's index
      and Geary's coefficient will be clarified and defined. One of theoretical
      findings is that Moran's index is a characteristic parameter of spatial weight
      matrices, so the selection of weight functions is very significant for
      autocorrelation analysis of geographical systems. A case study of 29 Chinese
      cities in 2000 will be employed to validate the innovatory models and methods.
      This work is a methodological study, which will simplify the process of
      autocorrelation analysis. The results of this study will lay the foundation for
      the scaling analysis of spatial autocorrelation. 

PMID- 23874593
TI  - Oxidative stress-induced DNA damage and repair in human peripheral blood
      mononuclear cells: protective role of hemoglobin.
AB  - BACKGROUND: DNA repair is a cellular defence mechanism responding to DNA damage
      caused in large part by oxidative stress. There is a controversy with regard to
      the effect of red blood cells on DNA damage and cellular response. AIM: To
      investigate the effect of red blood cells on H2O2-induced DNA damage and repair
      in human peripheral blood mononuclear cells. METHODS: DNA breaks were induced in
      peripheral blood mononuclear cells by H2O2 in the absence or presence of red
      blood cells, red blood cells hemolysate or hemoglobin. DNA repair was measured by
      (3)H-thymidine uptake, % double-stranded DNA was measured by fluorometric assay
      of DNA unwinding. DNA damage was measured by the comet assay and by the detection
      of histone H2AX phosphorylation. RESULTS: Red blood cells and red blood cells
      hemolysate reduced DNA repair in a dose-dependent manner. Red blood cells
      hemolysate reduced % double-stranded DNA, DNA damage and phosphorylation of
      histone H2AX. Hemoglobin had the same effect as red blood cells hemolysate on %
      double-stranded DNA. CONCLUSION: Red blood cells, via red blood cells hemolysate
      and hemoglobin, reduced the effect of oxidative stress on peripheral blood
      mononuclear cell DNA damage and phosphorylation of histone H2AX. Consequently,
      recruitment of DNA repair proteins diminished with reduction of DNA repair. This
      suggests that anemia predisposes to increased oxidative stress induced DNA
      damage, while a higher hemoglobin level provides protection against oxidative
      stress-induced DNA damage.

PMID- 23874591
TI  - Comprehensive gene expression profiling reveals synergistic functional networks
      in cerebral vessels after hypertension or hypercholesterolemia.
AB  - Atherosclerotic stenosis of cerebral arteries or intracranial large artery
      disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and
      Africans, but relatively little is known about gene expression changes in vessels
      at risk. This study compares comprehensive gene expression profiles in the middle
      cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk
      factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip
      method, or dietary supplementation with cholesterol. Microarray and Ingenuity
      Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes
      in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB,
      SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes
      related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of
      hypercholesterolemic rabbits showed differentially expressed genes that are
      surprisingly, linked to almost the same node molecules as the hypertensive
      rabbits, despite a relatively low percentage of 'common genes' (21 and 7%)
      between the two conditions. Up-regulated common genes were related to: UBC,
      SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated
      genes, related to UBC. Increased HNF4A message and protein were verified in the
      aorta. Together, these findings reveal similar nodal molecules and gene pathways
      in cerebral vessels affected by hypertension or hypercholesterolemia, which could
      be a basis for synergistic action of risk factors in the pathogenesis of ICLAD. 

PMID- 23874594
TI  - Are random trading strategies more successful than technical ones?
AB  - In this paper we explore the specific role of randomness in financial markets,
      inspired by the beneficial role of noise in many physical systems and in previous
      applications to complex socio-economic systems. After a short introduction, we
      study the performance of some of the most used trading strategies in predicting
      the dynamics of financial markets for different international stock exchange
      indexes, with the goal of comparing them to the performance of a completely
      random strategy. In this respect, historical data for FTSE-UK, FTSE-MIB, DAX, and
      S & P500 indexes are taken into account for a period of about 15-20 years (since
      their creation until today). 

PMID- 23874595
TI  - Biological signal processing with a genetic toggle switch.
AB  - Complex gene regulation requires responses that depend not only on the current
      levels of input signals but also on signals received in the past. In digital
      electronics, logic circuits with this property are referred to as sequential
      logic, in contrast to the simpler combinatorial logic without such internal
      memory. In molecular biology, memory is implemented in various forms such as
      biochemical modification of proteins or multistable gene circuits, but the design
      of the regulatory interface, which processes the input signals and the memory
      content, is often not well understood. Here, we explore design constraints for
      such regulatory interfaces using coarse-grained nonlinear models and stochastic
      simulations of detailed biochemical reaction networks. We test different designs
      for biological analogs of the most versatile memory element in digital
      electronics, the JK-latch. Our analysis shows that simple protein-protein
      interactions and protein-DNA binding are sufficient, in principle, to implement
      genetic circuits with the capabilities of a JK-latch. However, it also exposes
      fundamental limitations to its reliability, due to the fact that biological
      signal processing is asynchronous, in contrast to most digital electronics
      systems that feature a central clock to orchestrate the timing of all operations.
      We describe a seemingly natural way to improve the reliability by invoking the
      master-slave concept from digital electronics design. This concept could be
      useful to interpret the design of natural regulatory circuits, and for the design
      of synthetic biological systems. 

PMID- 23874596
TI  - The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir)
      Ribofuranosyl 5'-triphosphate towards influenza A virus polymerase.
AB  - T-705 (Favipiravir) is a broad-spectrum antiviral molecule currently in late
      stage clinical development for the treatment of influenza virus infection.
      Although it is believed that T-705 potency is mediated by its ribofuranosyl
      triphosphate (T-705 RTP) metabolite that could be mutagenic, the exact molecular
      interaction with the polymerase of influenza A virus (IAVpol) has not been
      elucidated. Here, we developed a biochemical assay to measure the kinetics of
      nucleotide incorporation by IAVpol in the elongation mode. In this assay, T-705
      RTP was recognized by IAVpol as an efficient substrate for incorporation to the
      RNA both as a guanosine and an adenosine analog. Compared to natural GTP and ATP,
      the discrimination of T-705 RTP was about 19- and 30-fold, respectively. Although
      the single incorporation of the ribonucleotide monophosphate form of T-705 did
      not efficiently block RNA synthesis, two consecutive incorporation events
      prevented further primer extension. In comparison, 3'-deoxy GTP caused immediate
      chain termination but was incorporated less efficiently by the enzyme, with a
      discrimination of 4,900-fold relative to natural GTP. Collectively, these results
      provide the first detailed biochemical characterization to evaluate the substrate
      efficiency and the inhibition potency of nucleotide analogs against influenza
      virus polymerase. The combination of ambiguous base-pairing with low
      discrimination of T-705 RTP provides a mechanistic basis for the in vitro
      mutagenic effect of T-705 towards influenza virus. 

PMID- 23874598
TI  - Effect of media use on HIV/AIDS-related knowledge and condom use in sub-Saharan
      Africa: a cross-sectional study.
AB  - It is known that the level of HIV/AIDS-related knowledge and the degree of condom
      use varies by socioeconomic status (SES). However, there is limited research on
      the effect of mass media use on HIV/AIDS-related cognitive and behavioral
      outcomes in low-income countries and how it might influence the association
      between SES and HIV-related outcomes. We investigated the moderating effect of
      media use on the relationship between SES and HIV/AIDS-related knowledge and
      condom use in sub-Saharan Africa in terms of communication inequalities. Cross
      sectional data from the Demographic Health Surveys from 13 sub-Saharan countries
      (2004-10) were pooled. Gender-stratified multivariable poisson regression of
      151,209 women and 68,890 men were used to calculate adjusted relative ratios and
      95% confidence intervals for the associations between SES, media use, HIV-related
      outcomes, and condom use. We found significant disparities in mass media use
      among people from different SES groups as well as among countries. Education and
      wealth are strongly and positively associated with awareness of HIV/AIDS and
      knowledge about transmission and prevention of HIV/AIDS and are significantly
      associated with condom use. These associations are attenuated when the use of
      various types of mass media is added to the models, with newspapers showing the
      strongest effect. The findings of this study suggest that media use has the
      potential to blunt the impact of socioeconomic status though not completely
      eliminate it. Thus, we need to pay attention to reducing communication
      inequalities among social groups and countries to moderate the effect of wealth
      and SES on HIV/AIDS. 

PMID- 23874597
TI  - Estimation of HIV incidence in a large, community-based, randomized clinical
      trial: NIMH project accept (HIV Prevention Trials Network 043).
AB  - BACKGROUND: National Institute of Mental Health Project Accept (HIV Prevention
      Trials Network [HPTN] 043) is a large, Phase III, community-randomized, HIV
      prevention trial conducted in 48 matched communities in Africa and Thailand. The
      study intervention included enhanced community-based voluntary counseling and
      testing. The primary endpoint was HIV incidence, assessed in a single, cross
      sectional, post-intervention survey of >50,000 participants. METHODS: HIV rapid
      tests were performed in-country. HIV status was confirmed at a central laboratory
      in the United States. HIV incidence was estimated using a multi-assay algorithm
      (MAA) that included the BED capture immunoassay, an avidity assay, CD4 cell
      count, and HIV viral load. RESULTS: Data from Thailand was not used in the
      endpoint analysis because HIV prevalence was low. Overall, 7,361 HIV infections
      were identified (4 acute, 3 early, and 7,354 established infections). Samples
      from established infections were analyzed using the MAA; 467 MAA positive samples
      were identified; 29 of those samples were excluded because they contained
      antiretroviral drugs. HIV prevalence was 16.5% (range at study sites: 5.93% to
      30.8%). HIV incidence was 1.60% (range at study sites: 0.78% to 3.90%).
      CONCLUSIONS: In this community-randomized trial, a MAA was used to estimate HIV
      incidence in a single, cross-sectional post-intervention survey. Results from
      this analysis were subsequently used to compare HIV incidence in the control and
      intervention communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT00203749.

PMID- 23874599
TI  - Cross-amplification and validation of SNPs conserved over 44 million years
      between seals and dogs.
AB  - High-density SNP arrays developed for humans and their companion species provide
      a rapid and convenient tool for generating SNP data in closely-related non-model
      organisms, but have not yet been widely applied to phylogenetically divergent
      taxa. Consequently, we used the CanineHD BeadChip to genotype 24 Antarctic fur
      seal (Arctocephalus gazella) individuals. Despite seals and dogs having diverged
      around 44 million years ago, 33,324 out of 173,662 loci (19.2%) could be
      genotyped, of which 173 were polymorphic and clearly interpretable. Two SNPs were
      validated using KASP genotyping assays, with the resulting genotypes being 100%
      concordant with those obtained from the high-density array. Two loci were also
      confirmed through in silico visualisation after mapping them to the fur seal
      transcriptome. Polymorphic SNPs were distributed broadly throughout the dog
      genome and did not differ significantly in proximity to genes from either
      monomorphic SNPs or those that failed to cross-amplify in seals. However, the
      nearest genes to polymorphic SNPs were significantly enriched for functional
      annotations relating to energy metabolism, suggesting a possible bias towards
      conserved regions of the genome. 

PMID- 23874601
TI  - Effect of land use history and pattern on soil carbon storage in arid region of
      Central Asia.
AB  - The purpose of this study is to investigate variations in soil organic carbon
      (SOC) in arid areas due to differences in the cultivation history, land use, and
      soil salinization. The study area is the lower Sangong River basin on the
      piedmont of the northern TianShan mountains, which experiences heavy land-use
      activities. In 1982 and 2005,127(152) and 74 (161) samples in old (new) oasis
      were collected from each site at the surface soil (i.e., 0-20 cm). The data
      reveal that the mean value of the surface soil organic carbon content of the old
      oasis was higher than that of the new oasis by 4.01 g/kg in 1982 and 3.79 g/kg in
      2005. Additionally, the soil organic carbon content decreased more rapidly in the
      newly reclaimed oasis than in the old oasis from 1982 to 2005. The spatial
      pattern of the SOC content was correlated with the exploitation time in the new
      oasis, the agricultural land use history, and the SOC content. The decreasing
      trend is clearer in the high SOC content area than in the low SOC content area.
      Farmland is the largest carbon pool in both the new and old oases. The carbon
      density of the old oasis was higher than that of the new oasis by 4.01 and 3.79
      g/kg in 1982 and 2005 respectively. The loss of SOC in the agricultural watershed
      of the arid region in NW China is obvious. Improvements of land management
      practices, such as no tillage, straw returning to soil, and balanced
      fertilization techniques, should be adopted to increase the SOC content. 

PMID- 23874600
TI  - Inhibition of beta2-microglobulin/hemochromatosis enhances radiation sensitivity
      by induction of iron overload in prostate cancer cells.
AB  - BACKGROUND: Bone metastasis is the most lethal form of several cancers. The beta2
      microglobulin (beta2-M)/hemochromatosis (HFE) complex plays an important role in
      cancer development and bone metastasis. We demonstrated previously that
      overexpression of beta2-M in prostate, breast, lung and renal cancer leads to
      increased bone metastasis in mouse models. Therefore, we hypothesized that beta2
      M is a rational target to treat prostate cancer bone metastasis. RESULTS: In this
      study, we demonstrate the role of beta2-M and its binding partner, HFE, in
      modulating radiation sensitivity and chemo-sensitivity of prostate cancer. By
      genetic deletion of beta2-M or HFE or using an anti-beta2-M antibody (Ab), we
      demonstrate that prostate cancer cells are sensitive to radiation in vitro and in
      vivo. Inhibition of beta2-M or HFE sensitized prostate cancer cells to radiation
      by increasing iron and reactive oxygen species and decreasing DNA repair and
      stress response proteins. Using xenograft mouse model, we demonstrate that anti
      beta2-M Ab sensitizes prostate cancer cells to radiation treatment. Additionally,
      anti-beta2-M Ab was able to prevent tumor growth in an immunocompetent
      spontaneous prostate cancer mouse model. Since bone metastasis is lethal, we used
      a bone xenograft model to test the ability of anti-beta2-M Ab and radiation to
      block tumor growth in the bone. Combination treatment significantly prevented
      tumor growth in the bone xenograft model by inhibiting beta2-M and inducing iron
      overload. In addition to radiation sensitive effects, inhibition of beta2-M
      sensitized prostate cancer cells to chemotherapeutic agents. CONCLUSION: Since
      prostate cancer bone metastatic patients have high beta2-M in the tumor tissue
      and in the secreted form, targeting beta2-M with anti-beta2-M Ab is a promising
      therapeutic agent. Additionally, inhibition of beta2-M sensitizes cancer cells to
      clinically used therapies such as radiation by inducing iron overload and
      decreasing DNA repair enzymes.

PMID- 23874602
TI  - Excessive cytokine response to rapid proliferation of highly pathogenic avian
      influenza viruses leads to fatal systemic capillary leakage in chickens.
AB  - Highly pathogenic avian influenza viruses (HPAIVs) cause lethal infection in
      chickens. Severe cases of HPAIV infections have been also reported in mammals,
      including humans. In both mammals and birds, the relationship between host
      cytokine response to the infection with HPAIVs and lethal outcome has not been
      well understood. In the present study, the highly pathogenic avian influenza
      viruses A/turkey/Italy/4580/1999 (H7N1) (Ty/Italy) and
      A/chicken/Netherlands/2586/2003 (H7N7) (Ck/NL) and the low pathogenic avian
      influenza virus (LPAIV) A/chicken/Ibaraki/1/2005 (H5N2) (Ck/Ibaraki) were
      intranasally inoculated into chickens. Ty/Italy replicated more extensively than
      Ck/NL in systemic tissues of the chickens, especially in the brain, and induced
      excessive mRNA expression of inflammatory and antiviral cytokines (IFN-gamma, IL
      1beta, IL-6, and IFN-alpha) in proportion to its proliferation. Using in situ
      hybridization, IL-6 mRNA was detected mainly in microglial nodules in the brain
      of the chickens infected with Ty/Italy. Capillary leakage assessed by Evans blue
      staining was observed in multiple organs, especially in the brains of the
      chickens infected with Ty/Italy, and was not observed in those infected with
      Ck/NL. In contrast, LPAIV caused only local infection in the chickens, with
      neither apparent cytokine expression nor capillary leakage in any tissue of the
      chickens. The present results indicate that an excessive cytokine response is
      induced by rapid and extensive proliferation of HPAIV and causes fatal multiple
      organ failure in chickens. 

PMID- 23874603
TI  - HIV-1 Vpr modulates macrophage metabolic pathways: a SILAC-based quantitative
      analysis.
AB  - Human immunodeficiency virus type 1 encoded viral protein Vpr is essential for
      infection of macrophages by HIV-1. Furthermore, these macrophages are resistant
      to cell death and are viral reservoir. However, the impact of Vpr on the
      macrophage proteome is yet to be comprehended. The goal of the present study was
      to use a stable-isotope labeling by amino acids in cell culture (SILAC) coupled
      with mass spectrometry-based proteomics approach to characterize the Vpr response
      in macrophages. Cultured human monocytic cells, U937, were differentiated into
      macrophages and transduced with adenovirus construct harboring the Vpr gene. More
      than 600 proteins were quantified in SILAC coupled with LC-MS/MS approach, among
      which 136 were significantly altered upon Vpr overexpression in macrophages.
      Quantified proteins were selected and clustered by biological functions, pathway
      and network analysis using Ingenuity computational pathway analysis. The
      proteomic data illustrating increase in abundance of enzymes in the glycolytic
      pathway (pentose phosphate and pyruvate metabolism) was further validated by
      western blot analysis. In addition, the proteomic data demonstrate down
      regulation of some key mitochondrial enzymes such as glutamate dehydrogenase 2
      (GLUD2), adenylate kinase 2 (AK2) and transketolase (TKT). Based on these
      observations we postulate that HIV-1 hijacks the macrophage glucose metabolism
      pathway via the Vpr-hypoxia inducible factor 1 alpha (HIF-1 alpha) axis to induce
      expression of hexokinase (HK), glucose-6-phosphate dehyrogenase (G6PD) and
      pyruvate kinase muscle type 2 (PKM2) that facilitates viral replication and
      biogenesis, and long-term survival of macrophages. Furthermore, dysregulation of
      mitochondrial glutamate metabolism in macrophages can contribute to
      neurodegeneration via neuroexcitotoxic mechanisms in the context of NeuroAIDS. 

PMID- 23874604
TI  - Transiently reduced PI3K/Akt activity drives the development of regulatory
      function in antigen-stimulated Naive T-cells.
AB  - Regulatory T-cells (Tregs) are central for immune homeostasis and divided in
      thymus-derived natural Tregs and peripherally induced iTreg. However, while
      phenotype and function of iTregs are well known, a remarkable lack exists in
      knowledge about signaling mechanisms leading to their generation from naive
      precursors in peripheral tissues. Using antigen specific naive T-cells from mice,
      we investigated CD4+ CD25+ FoxP3- iTreg induction during antigen-specific T-cell
      receptor (TCR) stimulation with weak antigen presenting cells (APC). We show that
      early signaling pathways such as ADAM-17-activation appeared similar in
      developing iTreg and effector cells (Teff) and both initially shedded CD62-L. But
      iTreg started reexpressing CD62-L after 24 h while Teff permanently downmodulated
      it. Furthermore, between 24 and 72 hours iTreg presented with significantly lower
      phosphorylation levels of Akt-S473 suggesting lower activity of the PI3K/Akt
      axis. This was associated with a higher expression of the Akt hydrophobic motif
      specific phosphatase PHLPP1 in iTreg. Importantly, the lack of costimulatory
      signals via CD28 from weak APC was central for the development of regulatory
      function in iTreg but not for the reappearance of CD62-L. Thus, T-cells display a
      window of sensitivity after onset of TCR triggering within which the intensity of
      the PI3K/Akt signal controls entry into either effector or regulatory pathways. 

PMID- 23874605
TI  - Function of FlhB, a membrane protein implicated in the bacterial flagellar type
      III secretion system.
AB  - The membrane protein FlhB is a highly conserved component of the flagellar
      secretion system, and it plays an active role in the regulation of protein
      export. In this study conserved properties of FlhB that are important for its
      function were investigated. Replacing the flhB gene (or part of the gene) in
      Salmonella typhimurium with the flhB gene of the distantly related bacterium
      Aquifex aeolicus greatly reduces motility. However, motility can be restored to
      some extent by spontaneous mutations in the part of flhB gene coding for the
      cytoplasmic domain of Aquifex FlhB. Structural analysis suggests that these
      mutations destabilize the structure. The secondary structure and stability of the
      mutated cytoplasmic fragments of FlhB have been studied by circular dichroism
      spectroscopy. The results suggest that conformational flexibility could be
      important for FlhB function. An extragenic suppressor mutation in the fliS gene,
      which decreases the affinity of FliS to FliC, partially restores motility of the
      FlhB substitution mutants. 

PMID- 23874606
TI  - Mapping and validation of the major sex-determining region in Nile tilapia
      (Oreochromis niloticus L.) Using RAD sequencing.
AB  - Sex in Oreochromis niloticus (Nile tilapia) is principally determined by an XX/XY
      locus but other genetic and environmental factors also influence sex ratio.
      Restriction Associated DNA (RAD) sequencing was used in two families derived from
      crossing XY males with females from an isogenic clonal line, in order to identify
      Single Nucleotide Polymorphisms (SNPs) and map the sex-determining region(s). We
      constructed a linkage map with 3,802 SNPs, which corresponded to 3,280
      informative markers, and identified a major sex-determining region on linkage
      group 1, explaining nearly 96% of the phenotypic variance. This sex-determining
      region was mapped in a 2 cM interval, corresponding to approximately 1.2 Mb in
      the O. niloticus draft genome. In order to validate this, a diverse family (4
      families; 96 individuals in total) and population (40 broodstock individuals)
      test panel were genotyped for five of the SNPs showing the highest association
      with phenotypic sex. From the expanded data set, SNPs Oni23063 and Oni28137
      showed the highest association, which persisted both in the case of family and
      population data. Across the entire dataset all females were found to be
      homozygous for these two SNPs. Males were heterozygous, with the exception of
      five individuals in the population and two in the family dataset. These fish
      possessed the homozygous genotype expected of females. Progeny sex ratios (over
      95% females) from two of the males with the "female" genotype indicated that they
      were neomales (XX males). Sex reversal induced by elevated temperature during
      sexual differentiation also resulted in phenotypic males with the "female"
      genotype. This study narrows down the region containing the main sex-determining
      locus, and provides genetic markers tightly linked to this locus, with an
      association that persisted across the population. These markers will be of use in
      refining the production of genetically male O. niloticus for aquaculture. 

PMID- 23874607
TI  - Optimization of ultrasonic-assisted extraction and radical-scavenging capacity of
      phenols and flavonoids from Clerodendrum cyrtophyllum Turcz leaves.
AB  - Ultrasonic-assisted extraction (UAE) was developed to extract phenolic and
      flavonoid antioxidants from Clerodendrum cyrtophyllum Turcz leaves. The optimal
      experimental parameters for antioxidant extraction from C. cyrtophyllum leaves
      were measured using single-factor experimentation combined with response surface
      methodology (RSM). Total phenolic content (TPC) and total flavonoid content (TFC)
      assays were used to quantify antioxidant compounds. Next, antioxidant radical
      scavenging capacity was measured using 2,2'-diphenyl-1-picrylhydrazyl (DPPH) and
      2,2' -azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) radicals.
      Optimized extraction conditions for UAE from C. cyrtophyllum leaves were as
      follows: 60.9% ethanol, 85.4 min, and 63.3 degrees C for maximal TPC extraction
      (16.8 +/- 0.2 mg GAE/g DW); 67.7% ethanol, 82.9 min, and 63.0  degrees C for
      maximal TFC extraction (49.3 +/- 0.4 mg RT/g DW); 48.8% ethanol, 85.1 min, and
      63.9  degrees C for maximal DPPH radical-scavenging capacity (86.8 +/- 0.2%); and
      50.6% ethanol, 81.3 min, and 63.4  degrees C for maximal ABTS radical-scavenging
      capacity (92.9 +/- 0.5%). Ethanol concentration was the most important factor in
      the extraction process. Our work offers optimal extraction conditions for C.
      cyrtophyllum as a potential source of natural antioxidants.

PMID- 23874609
TI  - Adult cardiac expression of the activating transcription factor 3, ATF3, promotes
      ventricular hypertrophy.
AB  - Cardiac hypertrophy is an adaptive response to various mechanophysical and
      pathophysiological stresses. However, when chronic stress is sustained, the
      beneficial response turns into a maladaptive process that eventually leads to
      heart failure. Although major advances in the treatment of patients have reduced
      mortality, there is a dire need for novel treatments for cardiac hypertrophy.
      Accordingly, considerable efforts are being directed towards developing mice
      models and understanding the processes that lead to cardiac hypertrophy. A case
      in point is ATF3, an immediate early transcription factor whose expression is
      induced in various cardiac stress models but has been reported to have
      conflicting functional significance in hypertrophy. To address this issue, we
      generated a transgenic mouse line with tetracycline-regulated ATF3 cardiac
      expression. These mice allowed us to study the consequence of ATF3 expression in
      the embryo or during the adult period, thus distinguishing the effect of ATF3 on
      development versus pathogenesis of cardiac dysfunction. Importantly, ATF3
      expression in adult mice resulted in rapid ventricles hypertrophy, heart
      dysfunction, and fibrosis. When combined with a phenylephrine-infusion pressure
      overload model, the ATF3 expressing mice displayed a severe outcome and heart
      dysfunction. In a complementary approach, ATF3 KO mice displayed a lower level of
      heart hypertrophy in the same pressure overload model. In summary, ectopic
      expression of ATF3 is sufficient to promote cardiac hypertrophy and exacerbates
      the deleterious effect of chronic pressure overload; conversely, ATF3 deletion
      protects the heart. Therefore, ATF3 may serve as an important drug target to
      reduce the detrimental consequences of heart hypertrophy. 

PMID- 23874608
TI  - Is beauty in the face of the beholder?
AB  - Opposing forces influence assortative mating so that one seeks a similar mate
      while at the same time avoiding inbreeding with close relatives. Thus, mate
      choice may be a balancing of phenotypic similarity and dissimilarity between
      partners. In the present study, we assessed the role of resemblance to Self's
      facial traits in judgments of physical attractiveness. Participants chose the
      most attractive face image of their romantic partner among several variants,
      where the faces were morphed so as to include only 22% of another face.
      Participants distinctly preferred a "Self-based morph" (i.e., their partner's
      face with a small amount of Self's face blended into it) to other morphed images.
      The Self-based morph was also preferred to the morph of their partner's face
      blended with the partner's same-sex "prototype", although the latter face was
      ("objectively") judged more attractive by other individuals. When ranking morphs
      differing in level of amalgamation (i.e., 11% vs. 22% vs. 33%) of another face,
      the 22% was chosen consistently as the preferred morph and, in particular, when
      Self was blended in the partner's face. A forced-choice signal-detection paradigm
      showed that the effect of self-resemblance operated at an unconscious level,
      since the same participants were unable to detect the presence of their own faces
      in the above morphs. We concluded that individuals, if given the opportunity,
      seek to promote "positive assortment" for Self's phenotype, especially when the
      level of similarity approaches an optimal point that is similar to Self without
      causing a conscious acknowledgment of the similarity. 

PMID- 23874610
TI  - Visuospatial function in early Alzheimer's disease--the use of the Visual Object
      and Space Perception (VOSP) battery.
AB  - Alzheimer's disease (AD) is the most frequent cause of dementia. The clinical
      symptoms of AD begin with impairment of memory and executive function followed by
      the gradual involvement of other functions, such as language, semantic knowledge,
      abstract thinking, attention, and visuospatial abilities. Visuospatial function
      involves the identification of a stimulus and its location and can be impaired at
      the beginning of AD. The Visual Object and Space Perception (VOSP) battery
      evaluates visuospatial function, while minimizing the interference of other
      cognitive functions. OBJECTIVES: To evaluate visuospatial function in early AD
      patients using the VOSP and determine cutoff scores to differentiate between
      cognitively healthy individuals and AD patients. METHODS: Thirty-one patients
      with mild AD and forty-four healthy elderly were evaluated using a
      neuropsychological battery and the VOSP. RESULTS: In the VOSP, the AD patients
      performed more poorly in all subtests examining object perception and in two
      subtests examining space perception (Number Location and Cube Analysis). The VOSP
      showed good accuracy and good correlation with tests measuring visuospatial
      function. CONCLUSION: Visuospatial function is impaired in the early stages of
      AD. The VOSP battery is a sensitive battery test for visuospatial deficits with
      minimal interference by other cognitive functions.

PMID- 23874611
TI  - South african papilionoid legumes are nodulated by diverse burkholderia with
      unique nodulation and nitrogen-fixation Loci.
AB  - The root-nodule bacteria of legumes endemic to the Cape Floristic Region are
      largely understudied, even though recent reports suggest the occurrence of
      nodulating Burkholderia species unique to the region. In this study, we
      considered the diversity and evolution of nodulating Burkholderia associated with
      the endemic papilionoid tribes Hypocalypteae and Podalyrieae. We identified
      distinct groups from verified rhizobial isolates by phylogenetic analyses of the
      16S rRNA and recA housekeeping gene regions. In order to gain insight into the
      evolution of the nodulation and diazotrophy of these rhizobia we analysed the
      genes encoding NifH and NodA. The majority of these 69 isolates appeared to be
      unique, potentially representing novel species. Evidence of horizontal gene
      transfer determining the symbiotic ability of these Cape Floristic Region
      isolates indicate evolutionary origins distinct from those of nodulating
      Burkholderia from elsewhere in the world. Overall, our findings suggest that
      Burkholderia species associated with fynbos legumes are highly diverse and their
      symbiotic abilities have unique ancestries. It is therefore possible that the
      evolution of these bacteria is closely linked to the diversification and
      establishment of legumes characteristic of the Cape Floristic Region. 

PMID- 23874612
TI  - RMOD: a tool for regulatory motif detection in signaling network.
AB  - Regulatory motifs are patterns of activation and inhibition that appear
      repeatedly in various signaling networks and that show specific regulatory
      properties. However, the network structures of regulatory motifs are highly
      diverse and complex, rendering their identification difficult. Here, we present a
      RMOD, a web-based system for the identification of regulatory motifs and their
      properties in signaling networks. RMOD finds various network structures of
      regulatory motifs by compressing the signaling network and detecting the
      compressed forms of regulatory motifs. To apply it into a large-scale signaling
      network, it adopts a new subgraph search algorithm using a novel data structure
      called path-tree, which is a tree structure composed of isomorphic graphs of
      query regulatory motifs. This algorithm was evaluated using various sizes of
      signaling networks generated from the integration of various human signaling
      pathways and it showed that the speed and scalability of this algorithm
      outperforms those of other algorithms. RMOD includes interactive analysis and
      auxiliary tools that make it possible to manipulate the whole processes from
      building signaling network and query regulatory motifs to analyzing regulatory
      motifs with graphical illustration and summarized descriptions. As a result, RMOD
      provides an integrated view of the regulatory motifs and mechanism underlying
      their regulatory motif activities within the signaling network. RMOD is freely
      accessible online at the following URL: http://pks.kaist.ac.kr/rmod. 

PMID- 23874613
TI  - Interactions between blood-borne Streptococcus pneumoniae and the blood-brain
      barrier preceding meningitis.
AB  - Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium and the
      predominant cause of bacterial meningitis. Meningitis is thought to occur as the
      result of pneumococci crossing the blood-brain barrier to invade the Central
      Nervous System (CNS); yet little is known about the steps preceding immediate
      disease development. To study the interactions between pneumococci and the
      vascular endothelium of the blood-brain barrier prior to meningitis we used an
      established bacteremia-derived meningitis model in combination with
      immunofluorescent imaging. Brain tissue of mice infected with S. pneumoniae
      strain TIGR4, a clinical meningitis isolate, was investigated for the location of
      the bacteria in relation to the brain vasculature in various compartments. We
      observed that S. pneumoniae adhered preferentially to the subarachnoid vessels,
      and subsequently, over time, reached the more internal cerebral areas including
      the cerebral cortex, septum, and choroid plexus. Interestingly, pneumococci were
      not detected in the choroid plexus till 8 hours-post infection. In contrast to
      the lungs, little to no leukocyte recruitment to the brain was observed over
      time, though Iba-1 and GFAP staining showed that microglia and astrocytes were
      activated as soon as 1 hour post-infection. Our results imply that i) the local
      immune system of the brain is activated immediately upon entry of bacteria into
      the bloodstream and that ii) adhesion to the blood brain barrier is
      spatiotemporally controlled at different sites throughout the brain. These
      results provide new information on these two important steps towards the
      development of pneumococcal meningitis. 

PMID- 23874614
TI  - Linking ClinicalTrials.gov and PubMed to track results of interventional human
      clinical trials.
AB  - OBJECTIVE: In an effort to understand how results of human clinical trials are
      made public, we analyze a large set of clinical trials registered at
      ClinicalTrials.gov, the world's largest clinical trial registry. MATERIALS AND
      METHODS: We considered two trial result artifacts: (1) existence of a trial
      result journal article that is formally linked to a registered trial or (2) the
      deposition of a trial's basic summary results within the registry. RESULTS: The
      study sample consisted of 8907 completed, interventional, phase 2-or-higher
      clinical trials that were completed in 2006-2009. The majority of trials (72.2%)
      had no structured trial-article link present. A total of 2367 trials (26.6%)
      deposited basic summary results within the registry. Of those, 969 trials (10.9%)
      were classified as trials with extended results and 1398 trials (15.7%) were
      classified as trials with only required basic results. The majority of the trials
      (54.8%) had no evidence of results, based on either linked result articles or
      basic summary results (silent trials), while a minimal number (9.2%) report
      results through both registry deposition and publication. DISCUSSION: Our study
      analyzes the body of linked knowledge around clinical trials (which we refer to
      as the "trialome"). Our results show that most trials do not report results and,
      for those that do, there is minimal overlap in the types of reporting. We
      identify several mechanisms by which the linkages between trials and their
      published results can be increased. CONCLUSION: Our study shows that even when
      combining publications and registry results, and despite availability of several
      information channels, trial sponsors do not sufficiently meet the mandate to
      inform the public either via a linked result publication or basic results
      submission.

PMID- 23874615
TI  - A six nuclear gene phylogeny of Citrus (Rutaceae) taking into account
      hybridization and lineage sorting.
AB  - BACKGROUND: Genus Citrus (Rutaceae) comprises many important cultivated species
      that generally hybridize easily. Phylogenetic study of a group showing extensive
      hybridization is challenging. Since the genus Citrus has diverged recently (4-12
      Ma), incomplete lineage sorting of ancestral polymorphisms is also likely to
      cause discrepancies among genes in phylogenetic inferences. Incongruence of gene
      trees is observed and it is essential to unravel the processes that cause
      inconsistencies in order to understand the phylogenetic relationships among the
      species. METHODOLOGY AND PRINCIPAL FINDINGS: (1) We generated phylogenetic trees
      using haplotype sequences of six low copy nuclear genes. (2) Published simple
      sequence repeat data were re-analyzed to study population structure and the
      results were compared with the phylogenetic trees constructed using sequence data
      and coalescence simulations. (3) To distinguish between hybridization and
      incomplete lineage sorting, we developed and utilized a coalescence simulation
      approach. In other studies, species trees have been inferred despite the
      possibility of hybridization having occurred and used to generate null
      distributions of the effect of lineage sorting alone (by coalescent simulation).
      Since this is problematic, we instead generate these distributions directly from
      observed gene trees. Of the six trees generated, we used the most resolved three
      to detect hybrids. We found that 11 of 33 samples appear to be affected by
      historical hybridization. Analysis of the remaining three genes supported the
      conclusions from the hybrid detection test. CONCLUSIONS: We have identified or
      confirmed probable hybrid origins for several Citrus cultivars using three
      different approaches-gene phylogenies, population structure analysis and
      coalescence simulation. Hybridization and incomplete lineage sorting were
      identified primarily based on differences among gene phylogenies with reference
      to null expectations via coalescence simulations. We conclude that identifying
      hybridization as a frequent cause of incongruence among gene trees is critical to
      correctly infer the phylogeny among species of Citrus.

PMID- 23874616
TI  - Magnetic resonance imaging interpretation in patients with sciatica who are
      potential candidates for lumbar disc surgery.
AB  - BACKGROUND: Magnetic Resonance Imaging (MRI) is considered the mainstay imaging
      investigation in patients suspected of lumbar disc herniations. Both imaging and
      clinical findings determine the final decision of surgery. The objective of this
      study was to assess MRI observer variation in patients with sciatica who are
      potential candidates for lumbar disc surgery. METHODS: Patients for this study
      were potential candidates (n = 395) for lumbar disc surgery who underwent MRI to
      assess eligibility for a randomized trial. Two neuroradiologists and one
      neurosurgeon independently evaluated all MRIs. A four point scale was used for
      both probability of disc herniation and root compression, ranging from definitely
      present to definitely absent. Multiple characteristics of the degenerated disc
      herniation were scored. For inter-agreement analysis absolute agreements and
      kappa coefficients were used. Kappa coefficients were categorized as poor
      (<0.00), slight (0.00-0.20), fair (0.21-0.40), moderate (0.41-0.60), substantial
      (0.61-0.80) and excellent (0.81-1.00) agreement. RESULTS: Excellent agreement was
      found on the affected disc level (kappa range 0.81-0.86) and the nerve root that
      most likely caused the sciatic symptoms (kappa range 0.86-0.89). Interobserver
      agreement was moderate to substantial for the probability of disc herniation
      (kappa range 0.57-0.77) and the probability of nerve root compression (kappa
      range 0.42-0.69). Absolute pairwise agreement among the readers ranged from 90
      94% regarding the question whether the probability of disc herniation on MRI was
      above or below 50%. Generally, moderate agreement was observed regarding the
      characteristics of the symptomatic disc level and of the herniated disc.
      CONCLUSION: The observer variation of MRI interpretation in potential candidates
      for lumbar disc surgery is satisfactory regarding characteristics most important
      in decision for surgery. However, there is considerable variation between
      observers in specific characteristics of the symptomatic disc level and herniated
      disc.

PMID- 23874618
TI  - NanoMiner - integrative human transcriptomics data resource for nanoparticle
      research.
AB  - The potential impact of nanoparticles on the environment and on human health has
      attracted considerable interest worldwide. The amount of transcriptomics data, in
      which tissues and cell lines are exposed to nanoparticles, increases year by
      year. In addition to the importance of the original findings, this data can have
      value in broader context when combined with other previously acquired and
      published results. In order to facilitate the efficient usage of the data, we
      have developed the NanoMiner web resource (http://nanominer.cs.tut.fi/), which
      contains 404 human transcriptome samples exposed to various types of
      nanoparticles. All the samples in NanoMiner have been annotated, preprocessed and
      normalized using standard methods that ensure the quality of the data analyses
      and enable the users to utilize the database systematically across the different
      experimental setups and platforms. With NanoMiner it is possible to 1) search and
      plot the expression profiles of one or several genes of interest, 2) cluster the
      samples within the datasets, 3) find differentially expressed genes in various
      nanoparticle studies, 4) detect the nanoparticles causing differential expression
      of selected genes, 5) analyze enriched Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathways and Gene Ontology (GO) terms for the detected genes and 6) search
      the expression values and differential expressions of the genes belonging to a
      specific KEGG pathway or Gene Ontology. In sum, NanoMiner database is a valuable
      collection of microarray data which can be also used as a data repository for
      future analyses. 

PMID- 23874617
TI  - Studies on the assembly characteristics of large subunit ribosomal proteins in S.
      cerevisae.
AB  - During the assembly process of ribosomal subunits, their structural components,
      the ribosomal RNAs (rRNAs) and the ribosomal proteins (r-proteins) have to join
      together in a highly dynamic and defined manner to enable the efficient formation
      of functional ribosomes. In this work, the assembly of large ribosomal subunit
      (LSU) r-proteins from the eukaryote S. cerevisiae was systematically
      investigated. Groups of LSU r-proteins with specific assembly characteristics
      were detected by comparing the protein composition of affinity purified early,
      middle, late or mature LSU (precursor) particles by semi-quantitative mass
      spectrometry. The impact of yeast LSU r-proteins rpL25, rpL2, rpL43, and rpL21 on
      the composition of intermediate to late nuclear LSU precursors was analyzed in
      more detail. Effects of these proteins on the assembly states of other r-proteins
      and on the transient LSU precursor association of several ribosome biogenesis
      factors, including Nog2, Rsa4 and Nop53, are discussed. 

PMID- 23874619
TI  - Large daily stock variation is associated with cardiovascular mortality in two
      cities of Guangdong, China.
AB  - OBJECTIVE: The current study aimed to examine the effects of daily change of the
      Shenzhen Stock Exchange Index on cardiovascular mortality in Guangzhou and
      Taishan, China. METHODS: Daily mortality and stock performance data during 2006
      2010 were collected to construct the time series for the two cities. A
      distributed lag non-linear model was utilized to examine the effect of daily
      stock index changes on cardiovascular mortality after controlling for potential
      confounding factors. RESULTS: We observed a delayed non-linear effect of the
      stock index change on cardiovascular mortality: both rising and declining of the
      stock index were associated with increased cardiovascular deaths. In Guangzhou,
      the 15-25 lag days cumulative relative risk of an 800 index drop was 2.08 (95%
      CI: 1.38-3.14), and 2.38 (95% CI: 1.31-4.31) for an 800 stock index increase on
      the cardiovascular mortality, respectively. In Taishan, the cumulative relative
      risk over 15-25 days lag was 1.65 (95% CI: 1.13-2.42) for an 800 index drop and
      2.08 (95% CI: 1.26-3.42) for an 800 index rising, respectively. CONCLUSIONS:
      Large ups and downs in daily stock index might be important predictor of
      cardiovascular mortality.

PMID- 23874620
TI  - Chronic cadmium treatment promotes oxidative stress and endothelial damage in
      isolated rat aorta.
AB  - Cadmium is a highly toxic metal that is present in phosphate fertilizers, and the
      incidence of cadmium poisoning in the general population has increased, mainly
      due to cigarette smoking. Once absorbed, cadmium accumulates in the tissues,
      causing harmful effects including high blood pressure, endothelial damage and
      oxidative stress. Oxidative stress is known to efficiently produce oxidized low
      density lipoprotein and consequently atherosclerosis, mainly in the aorta.
      However, the mechanisms through which endothelial damage is induced by cadmium
      have not been elucidated. Thus, the aim of this study was to investigate the
      effects of this metal in the isolated aorta and the possible role of oxidative
      stress. Rats received 100 mg.L(-1) cadmium chloride (CdCl2) in the drinking water
      or distilled water alone for four weeks. The pressor effect of cadmium was
      followed throughout the exposure period by tail plethysmography. At the end of
      the fourth week, the blood cadmium content was established, and the vascular
      reactivity of the isolated aorta to phenylephrine, acetylcholine and sodium
      nitroprusside was analyzed in the context of endothelium denudation and
      incubation with L-NAME, apocynin, losartan, enalapril, superoxide dismutase (SOD)
      or catalase. We observed an increased response to phenylephrine in cadmium
      treated rats. This increase was abolished by catalase and SOD incubation.
      Apocynin treatment reduced the phenylephrine response in both treatment groups,
      but its effect was greater in cadmium-treated rats, and NOX2 expression was
      greater in the cadmium group. These results suggested that cadmium in blood
      concentrations similar to those found in occupationally exposed populations is
      able to stimulate NOX2 expression, contributing to oxidative stress and reducing
      NO bioavailability, despite enhanced eNOS expression. These findings suggest that
      cadmium exposure promotes endothelial damage that might contribute to
      inflammation, vascular injury and the development of atherosclerosis. 

PMID- 23874621
TI  - the risk of cancer among Taiwanese female registered nurses: a nationwide
      retrospective study.
AB  - BACKGROUND: To evaluate the risk of cancer among Taiwanese female registered
      nurses (RNs) using a nationwide population-based dataset. METHODS: We recruited
      female RNs without antecedent cancer from the Taiwan National Health Insurance
      Research database during 2000-2010. Standardized incidence ratios (SIRs) of
      cancer were calculated. We also compared rates of Papanicolaou (Pap) smear use
      between the RNs and the general population matched by age and sex. RESULTS: A
      total of 2,077 cancers developed among 184,809 female RNs, with a follow-up of
      1,371,910 person-years (median follow-up of 7.86 years), leading to an increased
      SIR of 1.10 [95% confidence interval (CI) 1.05-1.15]. RNs aged between 40-59
      years also had a significantly increased SIR (1.14, 95% CI 1.08-1.21). For
      specific cancer types, RNs had an increased SIR for breast (1.28, 95% CI 1.19
      1.37), thyroid (1.26, 95% CI 1.10-1.43), lung and mediastinum (1.36, 95% CI 1.13
      1.62), and uterine cancers (1.23, 95% CI 1.01-1.49). A decreased SIR was found
      for cervix (0.48, 95% CI 0.37-0.61) and liver and biliary tract cancers (0.68,
      95% CI 0.50-0.90). Pap smear use averaged 5.80 times per person among female RNs
      aged 35 years or older and 5.50 times per person in the age-matched control group
      (p = 0.009). CONCLUSION: This study found that overall cancer risk was higher
      among female RNs than general population. For individual cancers, the risks of
      breast, lung, thyroid and uterine cancer were higher and the risks of cervix and
      liver cancer were lower than general population. The lower risk of cervical
      cancer might be partially explained by the increased use of Pap smears in the RNs
      group. Further large, unbiased population-based prospective studies are needed to
      investigate the association between nurses and cancer risk and identify the risk
      factors of cancer in nurses.

PMID- 23874623
TI  - Spatial access priority mapping (SAPM) with fishers: a quantitative GIS method
      for participatory planning.
AB  - Spatial management tools, such as marine spatial planning and marine protected
      areas, are playing an increasingly important role in attempts to improve marine
      management and accommodate conflicting needs. Robust data are needed to inform
      decisions among different planning options, and early inclusion of stakeholder
      involvement is widely regarded as vital for success. One of the biggest
      stakeholder groups, and the most likely to be adversely impacted by spatial
      restrictions, is the fishing community. In order to take their priorities into
      account, planners need to understand spatial variation in their perceived value
      of the sea. Here a readily accessible, novel method for quantitatively mapping
      fishers' spatial access priorities is presented. Spatial access priority mapping,
      or SAPM, uses only basic functions of standard spreadsheet and GIS software.
      Unlike the use of remote-sensing data, SAPM actively engages fishers in
      participatory mapping, documenting rather than inferring their priorities. By so
      doing, SAPM also facilitates the gathering of other useful data, such as local
      ecological knowledge. The method was tested and validated in Northern Ireland,
      where over 100 fishers participated in a semi-structured questionnaire and
      mapping exercise. The response rate was excellent, 97%, demonstrating fishers'
      willingness to be involved. The resultant maps are easily accessible and
      instantly informative, providing a very clear visual indication of which areas
      are most important for the fishers. The maps also provide quantitative data,
      which can be used to analyse the relative impact of different management options
      on the fishing industry and can be incorporated into planning software, such as
      MARXAN, to ensure that conservation goals can be met at minimum negative impact
      to the industry. This research shows how spatial access priority mapping can
      facilitate the early engagement of fishers and the ready incorporation of their
      priorities into the decision-making process in a transparent, quantitative way. 

PMID- 23874622
TI  - Coevolution of quantum and classical strategies on evolving random networks.
AB  - We study the coevolution of quantum and classical strategies on weighted and
      directed random networks in the realm of the prisoner's dilemma game. During the
      evolution, agents can break and rewire their links with the aim of maximizing
      payoffs, and they can also adjust the weights to indicate preferences, either
      positive or negative, towards their neighbors. The network structure itself is
      thus also subject to evolution. Importantly, the directionality of links does not
      affect the accumulation of payoffs nor the strategy transfers, but serves only to
      designate the owner of each particular link and with it the right to adjust the
      link as needed. We show that quantum strategies outperform classical strategies,
      and that the critical temptation to defect at which cooperative behavior can be
      maintained rises, if the network structure is updated frequently. Punishing
      neighbors by reducing the weights of their links also plays an important role in
      maintaining cooperation under adverse conditions. We find that the self
      organization of the initially random network structure, driven by the
      evolutionary competition between quantum and classical strategies, leads to the
      spontaneous emergence of small average path length and a large clustering
      coefficient. 

PMID- 23874624
TI  - Immunological profile of silent brain infarction and lacunar stroke.
AB  - Neuroinflammation is believed to be involved in the pathophysiological mechanisms
      of silent brain infarcts (SBI). However, the immunological profile of SBI has
      been scarcely investigated. In the context of a national research project named
      SILENCE, aimed at investigating clinical, biochemical and pathogenic features of
      SBI, we have measured the plasma profile of some inflammatory-related molecules
      in SBI patients (n = 21), patients with recent lacunar infarcts (LI, n = 28) and
      healthy controls (n = 31), consecutively enrolled in four Italian centres. A
      panel of chemokines (MIG, CTACK, IL16, SDF1a, MCP1), growth factors (SCF, SCGFb,
      HGF, IL3), immunoglobulin-type adhesion molecules (ICAM1, VCAM1), proinflammatory
      cytokines (IL18, INFa2, MIF, IL12p40), cell surface receptors on T-cells (IL2Ra),
      and inductors of apoptosis (TRAIL) was assessed in plasma samples by Luminex
      xMAPTM technology. Immunological parameters were compared using non-parametric
      statistics and performance to distinguish SBI and LI was evaluated by receiver
      operating characteristic (ROC) analysis. Plasma levels of ICAM1 were
      significantly higher in both SBI and LI patients as compared to controls
      (SBI>=LI>Ctrl). A different trend was observed for IL16 (SBI<LI>Ctrl), SCF
      (LI<SBI>Ctrl) and SCGFb (SBI>LI<Ctrl). SBI subjects had significantly increased
      levels of MIG when compared to controls (LI<=SBI>Ctrl) and IL18 when compared to
      LI patients (Ctrl<=SBI>LI). All the other immunological markers did not
      significantly differ among groups. According to ROC analysis, the best predictor
      for SBI condition was the chemokine MIG (AUC = 0.84, sensitivity 86%, specificity
      77%), while SCF had the best performance in distinguishing LI patients (AUC =
      0.84, sensitivity 86%, specificity 68%). These results confirm the involvement of
      inflammatory processes in cerebrovascular disorders, particularly in SBI, a very
      common age-related condition. The differences in plasma profile of inflammatory
      molecules may underlie different pathological mechanisms in SBI and LI patients. 

PMID- 23874625
TI  - Invasion is a community affair: Clandestine followers in the bacterial community
      associated to green algae, Caulerpa racemosa, track the invasion source.
AB  - Biological invasions rank amongst the most deleterious components of global
      change inducing alterations from genes to ecosystems. The genetic characteristics
      of introduced pools of individuals greatly influence the capacity of introduced
      species to establish and expand. The recently demonstrated heritability of
      microbial communities associated to individual genotypes of primary producers
      makes them a potentially essential element of the evolution and adaptability of
      their hosts. Here, we characterized the bacterial communities associated to
      native and non-native populations of the marine green macroalga Caulerparacemosa
      through pyrosequencing, and explored their potential role on the strikingly
      invasive trajectory of their host in the Mediterranean. The similarity of
      endophytic bacterial communities from the native Australian range and several
      Mediterranean locations confirmed the origin of invasion and revealed distinct
      communities associated to a second Mediterranean variety of C. racemosa long
      reported in the Mediterranean. Comparative analysis of these two groups
      demonstrated the stability of the composition of bacterial communities through
      the successive steps of introduction and invasion and suggested the vertical
      transmission of some major bacterial OTUs. Indirect inferences on the taxonomic
      identity and associated metabolism of bacterial lineages showed a striking
      consistency with sediment upheaval conditions associated to the expansion of
      their invasive host and to the decline of native species. These results
      demonstrate that bacterial communities can be an effective tracer of the origin
      of invasion and support their potential role in their eukaryotic host's
      adaptation to new environments. They put forward the critical need to consider
      the 'meta-organism' encompassing both the host and associated micro-organisms, to
      unravel the origins, causes and mechanisms underlying biological invasions. 

PMID- 23874626
TI  - Changes in natural Foxp3(+)Treg but not mucosally-imprinted
      CD62L(neg)CD38(+)Foxp3(+)Treg in the circulation of celiac disease patients.
AB  - BACKGROUND: Celiac disease (CD) is an intestinal inflammation driven by gluten
      reactive CD4(+) T cells. Due to lack of selective markers it has not been
      determined whether defects in inducible regulatory T cell (Treg) differentiation
      are associated with CD. This is of importance as changes in numbers of induced
      Treg could be indicative of defects in mucosal tolerance development in CD.
      Recently, we have shown that, after encounter of retinoic acid during
      differentiation, circulating gut-imprinted T cells express CD62L(neg)CD38(+).
      Using this new phenotype, we now determined whether alterations occur in the
      frequency of natural CD62L(+)Foxp3(+) Treg or mucosally-imprinted
      CD62L(neg)CD38(+)Foxp3(+) Treg in peripheral blood of CD patients. In particular,
      we compared pediatric CD, aiming to select for disease at onset, with adult CD.
      METHODS: Cell surface markers, intracellular Foxp3 and Helios were determined by
      flow cytometry. Foxp3 expression was also detected by immunohistochemistry in
      duodenal tissue of CD patients. RESULTS: In children, the percentages of
      peripheral blood CD4(+)Foxp3(+) Treg were comparable between CD patients and
      healthy age-matched controls. Differentiation between natural and mucosally
      imprinted Treg on the basis of CD62L and CD38 did not uncover differences in
      Foxp3. In adult patients on gluten-free diet and in refractory CD increased
      percentages of circulating natural CD62L(+)Foxp3(+) Treg, but normal mucosally
      imprinted CD62L(neg)CD38(+)Foxp3(+) Treg frequencies were observed. CONCLUSIONS:
      Our data exclude that significant numeric deficiency of mucosally-imprinted or
      natural Foxp3(+) Treg explains exuberant effector responses in CD. Changes in
      natural Foxp3(+) Treg occur in a subset of adult patients on a gluten-free diet
      and in refractory CD patients.

PMID- 23874627
TI  - Inhibition of PbGP43 expression may suggest that gp43 is a virulence factor in
      Paracoccidioides brasiliensis.
AB  - Glycoprotein gp43 is an immunodominant diagnostic antigen for
      paracoccidioidomycosis caused by Paracoccidioides brasiliensis. It is abundantly
      secreted in isolates such as Pb339. It is structurally related to beta-1,3
      exoglucanases, however inactive. Its function in fungal biology is unknown, but
      it elicits humoral, innate and protective cellular immune responses; it binds to
      extracellular matrix-associated proteins. In this study we applied an antisense
      RNA (aRNA) technology and Agrobacterium tumefaciens-mediated transformation to
      generate mitotically stable PbGP43 mutants (PbGP43 aRNA) derived from wild type
      Pb339 to study its role in P. brasiliensis biology and during infection. Control
      PbEV was transformed with empty vector. Growth curve, cell vitality and
      morphology of PbGP43 aRNA mutants were indistinguishable from those of controls.
      PbGP43 expression was reduced 80-85% in mutants 1 and 2, as determined by real
      time PCR, correlating with a massive decrease in gp43 expression. This was shown
      by immunoblotting of culture supernatants revealed with anti-gp43 mouse
      monoclonal and rabbit polyclonal antibodies, and also by affinity-ligand assays
      of extracellular molecules with laminin and fibronectin. In vitro, there was
      significantly increased TNF-alpha production and reduced yeast recovery when
      PbGP43 aRNA1 was exposed to IFN-gamma-stimulated macrophages, suggesting reduced
      binding/uptake and/or increased killing. In vivo, fungal burden in lungs of
      BALB/c mice infected with silenced mutant was negligible and associated with
      decreased lung IotaLambda-10 and IL-6. Therefore, our results correlated low gp43
      expression with lower pathogenicity in mice, but that will be definitely proven
      when PbGP43 knockouts become available. This is the first study of gp43 using
      genetically modified P. brasiliensis. 

PMID- 23874628
TI  - Functional roles of FgLaeA in controlling secondary metabolism, sexual
      development, and virulence in Fusarium graminearum.
AB  - Fusarium graminearum, the causal agent of Fusarium head blight in cereal crops,
      produces mycotoxins such as trichothecenes and zearalenone in infected plants.
      Here, we focused on the function of FgLaeA in F. graminearum, a homolog of
      Aspergillus nidulans LaeA encoding the global regulator for both secondary
      metabolism and sexual development. Prior to gene analysis, we constructed a novel
      luciferase reporter system consisting of a transgenic F. graminearum strain
      expressing a firefly luciferase gene under control of the promoter for either
      TRI6 or ZEB2 controlling the biosynthesis of these mycotoxins. Targeted deletion
      of FgLaeA led to a dramatic reduction of luminescence in reporter strains,
      indicating that FgLaeA controls the expression of these transcription factors in
      F. graminearum; reduced toxin accumulation was further confirmed by GC-MS
      analysis. Overexpression of FgLaeA caused the increased production of
      trichothecenes and additional metabolites. RNA seq-analysis revealed that gene
      member(s) belonging to ~70% of total tentative gene clusters, which were
      previously proposed, were differentially expressed in the DeltaFgLaeA strain. In
      addition, DeltaFgLaeA strains exhibited an earlier induction of sexual fruiting
      body (perithecia) formation and drastically reduced disease symptoms in wheat,
      indicating that FgLaeA seems to negatively control perithecial induction, but
      positively control virulence toward the host plant. FgLaeA was constitutively
      expressed under both mycotoxin production and sexual development conditions.
      Overexpression of a GFP-FgLaeA fusion construct in the DeltaFgLaeA strain
      restored all phenotypic changes to wild-type levels and led to constitutive
      expression of GFP in both nuclei and cytoplasm at different developmental stages.
      A split luciferase assay demonstrated that FgLaeA was able to interact with
      FgVeA, a homolog of A. nidulans veA. Taken together, these results demonstrate
      that FgLaeA, a member of putative FgVeA complex, controls secondary metabolism,
      sexual development, and virulence in F. graminearum, although the specific
      regulation pattern differs from that of LaeA in A. nidulans.

PMID- 23874629
TI  - Health disparities from economic burden of diabetes in middle-income countries:
      evidence from Mexico.
AB  - The rapid growth of diabetes in middle-income countries is generating disparities
      in global health. In this context we conducted a study to quantify the health
      disparities from the economic burden of diabetes in Mexico. Evaluative research
      based on a longitudinal design, using cost methodology by instrumentation. For
      the estimation of epidemiological changes during the 2010-2012 period, several
      probabilistic models were developed using the Box-Jenkins technique. The
      financial requirements were obtained from expected case management costs by
      disease and the application of an econometric adjustment factor to control the
      effects of inflation. Comparing the economic impact in 2010 versus 2012 (p<0.05),
      there was a 33% increase in financial requirements. The total amount for diabetes
      in 2011 (US dollars) was $7.7 billion. It includes $3.4 billion in direct costs
      and $4.3 in indirect costs. The total direct costs were $.4 billion to the
      Ministry of Health (SSA), serving the uninsured population; $1.2 to the
      institutions serving the insured population (Mexican Institute for Social
      Security-IMSS-, and Institute for Social Security and Services for State Workers
      ISSSTE-); $1.8 to users; and $.1 to Private Health Insurance (PHI). If the risk
      factors and the different health care models remain as they currently are in the
      analyzed institutions, health disparities in terms of financial implications will
      have the greatest impact on users' pockets. In middle-income countries, health
      disparities generated by the economic burden of diabetes is one of the main
      reasons for catastrophic health expenditure. Health disparities generated by the
      economic burden of diabetes suggests the need to design and review the current
      organization of health systems and the relevance of moving from biomedical models
      and curative health care to preventive and socio-medical models to meet expected
      challenges from diseases like diabetes in middle-income countries. 

PMID- 23874630
TI  - A high frequency of circulating th22 and th17 cells in patients with new onset
      graves' disease.
AB  - T-helper (Th) 22 and Th17 cells are involved in the pathogenesis of autoimmune
      diseases. However, their roles in the pathogenesis of Graves'disease (GD) are
      unclear. This study is aimed at examining the frequency of peripheral blood Th22,
      Th17, and Th1 cells and the levels of plasma IL-22, IL-17, and IFN-gamma in
      patients with GD. A total of 27 patients with new onset GD and 27 gender- and age
      matched healthy controls (HC) were examined for the frequency of peripheral blood
      Th22, Th17, and IFN-gamma cells by flow cytometry. The concentrations of plasma
      IL-22, IL-17, and IFN-gamma were examined by enzyme-linked immunosorbent assay.
      The levels of serum TSHR antibodies (A-TSHR), free triiodothyronine (FT3), free
      thyroxine (FT4), and thyroid stimulating hormone (TSH) were examined by
      radioimmunoassay and chemiluminescent assay, respectively. The levels of serum
      TSAb were examined by enzyme-linked immunosorbent assay. In comparison with those
      in the HC, significantly elevated percentages of Th22 and Th17 cells, but not Th1
      cells, and increased levels of plasma IL-22 and IL-17, but not IFN-gamma, were
      detected in GD patients (P<0.0001, for both). The percentages of both Th22 and
      Th17 cells and the levels of plasma IL-22 and IL-17 were correlated positively
      with the levels of serum TSAb in GD patients (r = 0.7944, P<0.0001; r = 0.8110,
      P<0.0001; r = 0.7101, p<0.0001; r = 0.7407, p<0.0001, respectively). Th22 and
      Th17 cells may contribute to the pathogenesis of GD. 

PMID- 23874631
TI  - Respiratory function and changes in lung epithelium biomarkers after a short
      training intervention in chlorinated vs. ozone indoor pools.
AB  - BACKGROUND: Swimming in indoor pools treated with combined chemical treatments
      (e.g. ozone) may reduce direct exposure to disinfection byproducts and thus have
      less negative effects on respiratory function compared to chlorinated pools. The
      aim of this study is to analyze the effects of a short-term training intervention
      on respiratory function and lung epithelial damage in adults exercising in indoor
      swimming pool waters treated with different disinfection methods (chlorine vs.
      ozone with bromine). METHODS: Lung permeability biomakers [surfactant protein D
      (SP-D) and Clara cell secretory protein (CC16) in plasma] and forced expiratory
      volumes and flow (FEV1, FVC and FEF25-75) were measured in 39 healthy adults.
      Thirteen participants swam during 20 sessions in a chlorinated pool (CP), 13
      performed and equivolumic intervention in an ozone pool (OP) and 13 were included
      in a control group (CG) without exposition. RESULTS: Median plasma CC16 levels
      increased in CP swimmers (4.27 +/- 3.29 and 6.62 +/- 5.51 ug/L, p=0.01, pre and
      post intervention respectively) while no significant changes in OP and CG
      participants were found. No significant changes in median plasma SP-D levels were
      found in any of the groups after the training period. FVC increased in OP (4.26
      +/- 0.86 and 4.43 +/- 0.92 L, p<0.01) and CP swimmers (4.25 +/- 0.86 and 4.35 +/-
      0.85 L, p<0.01). FEV1 only increased in OP swimmers (3.50 +/- 0.65 and 3.59 +/-
      0.67, p=0.02) and FEF25-75 decreased in CP swimmers (3.70 +/- 0.87 and 3.37 +/-
      0.67, p=0.02). CONCLUSION: Despite lung function being similar in both groups, a
      higher lung permeability in CP compared to OP swimmers was found after a short
      term swimming program. Combined chemical treatments for swimming pools such as
      ozone seem to have less impact on lung epithelial of swimmers compared to
      chlorinated treated pools.

PMID- 23874632
TI  - Foraging patch selection in winter: a balance between predation risk and
      thermoregulation benefit.
AB  - In winter, foraging activity is intended to optimize food search while minimizing
      both thermoregulation costs and predation risk. Here we quantify the relative
      importance of thermoregulation and predation in foraging patch selection of
      woodland birds wintering in a Mediterranean montane forest. Specifically, we
      account for thermoregulation benefits related to temperature, and predation risk
      associated with both illumination of the feeding patch and distance to the
      nearest refuge provided by vegetation. We measured the amount of time that 38
      marked individual birds belonging to five small passerine species spent foraging
      at artificial feeders. Feeders were located in forest patches that vary in
      distance to protective cover and exposure to sun radiation; temperature and
      illumination were registered locally by data loggers. Our results support the
      influence of both thermoregulation benefits and predation costs on feeding patch
      choice. The influence of distance to refuge (negative relationship) was nearly
      three times higher than that of temperature (positive relationship) in
      determining total foraging time spent at a patch. Light intensity had a
      negligible and no significant effect. This pattern was generalizable among
      species and individuals within species, and highlights the preponderance of
      latent predation risk over thermoregulation benefits on foraging decisions of
      birds wintering in temperate Mediterranean forests. 

PMID- 23874633
TI  - High-content analysis of sequential events during the early phase of influenza A
      virus infection.
AB  - Influenza A virus (IAV) represents a worldwide threat to public health by causing
      severe morbidity and mortality every year. Due to high mutation rate, new strains
      of IAV emerge frequently. These IAVs are often drug-resistant and require vaccine
      reformulation. A promising approach to circumvent this problem is to target host
      cell determinants crucial for IAV infection, but dispensable for the cell.
      Several RNAi-based screens have identified about one thousand cellular factors
      that promote IAV infection. However, systematic analyses to determine their
      specific functions are lacking. To address this issue, we developed quantitative,
      imaging-based assays to dissect seven consecutive steps in the early phases of
      IAV infection in tissue culture cells. The entry steps for which we developed the
      assays were: virus binding to the cell membrane, endocytosis, exposure to low pH
      in endocytic vacuoles, acid-activated fusion of viral envelope with the vacuolar
      membrane, nucleocapsid uncoating in the cytosol, nuclear import of viral
      ribonucleoproteins, and expression of the viral nucleoprotein. We adapted the
      assays to automated microscopy and optimized them for high-content screening. To
      quantify the image data, we performed both single and multi-parametric analyses,
      in combination with machine learning. By time-course experiments, we determined
      the optimal time points for each assay. Our quality control experiments showed
      that the assays were sufficiently robust for high-content analysis. The methods
      we describe in this study provide a powerful high-throughput platform to
      understand the host cell processes, which can eventually lead to the discovery of
      novel anti-pathogen strategies. 

PMID- 23874635
TI  - Interactions of grazing history, cattle removal and time since rain drive
      divergent short-term responses by desert biota.
AB  - Arid grasslands are used worldwide for grazing by domestic livestock, generating
      debate about how this pastoral enterprise may influence native desert biota. One
      approach to resolving this question is to experimentally reduce livestock numbers
      and measure the effects. However, a key challenge in doing this is that
      historical grazing impacts are likely to be cumulative and may therefore confound
      comparisons of the short-term responses of desert biota to changes in stocking
      levels. Arid areas are also subject to infrequent flooding rainfalls that drive
      productivity and dramatically alter abundances of flora and fauna. We took
      advantage of an opportunity to study the recent effects of a property-scale
      cattle removal on two properties with similarly varied grazing histories in
      central Australia. Following the removal of cattle in 2006 and before and after a
      significant rainfall event at the beginning of 2007, we sampled vegetation and
      small vertebrates on eight occasions until October 2008. Our results revealed
      significant interactions of time of survey with both grazing history and grazing
      removal for vascular plants, small mammals and reptiles. The mammals exhibited a
      three-way interaction of time, grazing history and grazing removal, thus
      highlighting the importance of careful sampling designs and timing for future
      monitoring. The strongest response to the cessation of grazing after two years
      was depressed reproductive output of plants in areas where cattle continued to
      graze. Our results confirm that neither vegetation nor small vertebrates
      necessarily respond immediately to the removal of livestock, but that rainfall
      events and cumulative grazing history are key determinants of floral and faunal
      performance in grassland landscapes with low and variable rainfall. We suggest
      that improved assessments could be made of the health of arid grazing
      environments if long-term monitoring were implemented to track the complex
      interactions that influence how native biota respond to grazing. 

PMID- 23874634
TI  - Male-biased genes in catfish as revealed by RNA-Seq analysis of the testis
      transcriptome.
AB  - BACKGROUND: Catfish has a male-heterogametic (XY) sex determination system, but
      genes involved in gonadogenesis, spermatogenesis, testicular determination, and
      sex determination are poorly understood. As a first step of understanding the
      transcriptome of the testis, here, we conducted RNA-Seq analysis using high
      throughput Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: A total of 269.6
      million high quality reads were assembled into 193,462 contigs with a N50 length
      of 806 bp. Of these contigs, 67,923 contigs had hits to a set of 25,307 unigenes,
      including 167 unique genes that had not been previously identified in catfish. A
      meta-analysis of expressed genes in the testis and in the gynogen (double haploid
      female) allowed the identification of 5,450 genes that are preferentially
      expressed in the testis, providing a pool of putative male-biased genes. Gene
      ontology and annotation analysis suggested that many of these male-biased genes
      were involved in gonadogenesis, spermatogenesis, testicular determination,
      gametogenesis, gonad differentiation, and possibly sex determination.
      CONCLUSION/SIGNIFICANCE: We provide the first transcriptome-level analysis of the
      catfish testis. Our analysis would lay the basis for sequential follow-up studies
      of genes involved in sex determination and differentiation in catfish.

PMID- 23874636
TI  - Dual regulatory roles of human AP-endonuclease (APE1/Ref-1) in CDKN1A/p21
      expression.
AB  - The human AP-endonuclease (APE1/Ref-1), an essential multifunctional protein
      involved in repair of oxidative DNA damage as well as in transcriptional
      regulation, is often overexpressed in tumor cells. APE1 was earlier shown to
      stimulate p53's DNA binding and its transactivation function in the expression of
      cyclin-dependent kinase inhibitor p21 (CDKN1A) gene. Here, we show APE1's stable
      binding to p53 cis elements which are required for p53-mediated activation of p21
      in p53-expressing wild type HCT116 cells. However, surprisingly, we observed APE1
      dependent repression of p21 in isogenic p53-null HCT116 cells. Ectopic expression
      of p53 in the p53-null cells abrogated this repression suggesting that APE1's
      negative regulatory role in p21 expression is dependent on the p53 status. We
      then identified APE1's another binding site in p21's proximal promoter region
      containing cis elements for AP4, a repressor of p21. Interestingly, APE1 and AP4
      showed mutual dependence for p21 repression. Moreover, ectopic p53 in p53-null
      cells inhibited AP4's association with APE1, their binding to the promoter and
      p21 repression. These results together establish APE1's role as a co-activator or
      co-repressor of p21 gene, dependent on p53 status. It is thus likely that APE1
      overexpression and inactivation of p53, often observed in tumor cells, promote
      tumor cell proliferation by constitutively downregulating p21 expression. 

PMID- 23874637
TI  - An apoptosis-associated mammary protein deficiency leads to enhanced production
      of IgM antibodies against multiple damage-associated molecules.
AB  - Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that binds to
      apoptotic cells by recognizing phosphatidylserine and enhances the engulfment of
      apoptotic cells by macrophages. Many apoptotic cells are left unengulfed in the
      germinal centers of the spleen in the MFG-E8-deficient (MFG-E8(-/-)) mice, and
      these mice develop an autoimmune disease resembling human systemic lupus
      erythematosus. We found that the MFG-E8 deficiency was accompanied by the
      increased production of immunoglobulins. Further Western blot and ELISA analyses
      validated the increase in the IgM levels in the MFG-E8(-/-) mice. It was also
      revealed that the sera from the MFG-E8(-/-) mice cross-reacted with oxidation
      specific epitopes generated upon incubation of serum albumin with the peroxidized
      lipids. Among the modified proteins with several unsaturated aldehydes of chain
      lengths varying from three to nine carbons, the MFG-E8(-/-) mice sera exclusively
      cross-reacted with the protein-bound 4-oxo-2-nonenal (ONE), a highly reactive
      aldehyde originating from the peroxidation of omega6 polyunsaturated fatty acids.
      In addition, the IgM monoclonal antibodies (mAbs) that selectively cross-reacted
      with the ONE-modified proteins were generated from the MFG-E8(-/-) mice. A subset
      of the ONE-specific IgM mAbs significantly recognized the late apoptotic and
      necrotic cells and enhanced the phagocytosis by macrophages. These data
      demonstrate that the impairment of the phagocytic clearance of apoptotic cells
      through MFG-E8 can lead to the generation of natural antibodies, which may play a
      critical role in removing multiple damage-associated molecules, including
      oxidation-specific epitopes and late apoptotic/necrotic cells. 

PMID- 23874638
TI  - Memory color effect induced by familiarity of brand logos.
AB  - BACKGROUND: When people are asked to adjust the color of familiar objects such as
      fruits until they appear achromatic, the subjective gray points of the objects
      are shifted away from the physical gray points in a direction opposite to the
      memory color (memory color effect). It is still unclear whether the discrepancy
      between memorized and actual colors of objects is dependent on the familiarity of
      the objects. Here, we conducted two experiments in order to examine the
      relationship between the degree of a subject's familiarity with objects and the
      degree of the memory color effect by using logographs of food and beverage
      companies. METHODS AND FINDINGS: In Experiment 1, we measured the memory color
      effects of logos which varied in terms of their familiarity (high, middle, or
      low). Results demonstrate that the memory color effect occurs only in the high
      familiarity condition, but not in the middle- and low-familiarity conditions.
      Furthermore, there is a positive correlation between the memory color effect and
      the actual number of domestic stores of the brand. In Experiment 2, we assessed
      the semantic association between logos and food/beverage names by using a
      semantic priming task to elucidate whether the memory color effect of logos
      relates to consumer brand cognition, and found that the semantic associations
      between logos and food/beverage names in the high-familiarity brands were
      stronger than those in the low-familiarity brands only when the logos were
      colored correctly, but not when they were appropriately or inappropriately
      colored, or achromatic. CONCLUSION: The current results provide behavioral
      evidence of the relationship between the familiarity of objects and the memory
      color effect and suggest that the memory color effect increases with the
      familiarity of objects, albeit not constantly.

PMID- 23874639
TI  - Nucleophosmin1 is a negative regulator of the small GTPase Rac1.
AB  - The Rac1 GTPase is a critical regulator of cytoskeletal dynamics and controls
      many biological processes, such as cell migration, cell-cell contacts, cellular
      growth and cell division. These complex processes are controlled by Rac1
      signaling through effector proteins. We have previously identified several
      effector proteins of Rac1 that also act as Rac1 regulatory proteins, including
      caveolin-1 and PACSIN2. Here, we report that Rac1 interacts through its C
      terminus with nucleophosmin1 (NPM1), a multifunctional nucleo-cytoplasmic
      shuttling protein with oncogenic properties. We show that Rac1 controls NPM1
      subcellular localization. In cells expressing active Rac1, NPM1 translocates from
      the nucleus to the cytoplasm. In addition, Rac1 regulates the localization of the
      phosphorylated pool of NPM1 as this pool translocated from the nucleus to the
      cytosol in cells expressing activated Rac1. Conversely, we found that expression
      of NPM1 limits Rac1 GTP loading and cell spreading. In conclusion, this study
      identifies NPM1 as a novel, negative regulator of Rac1. 

PMID- 23874640
TI  - A template-free, ultra-adsorbing, high surface area carbonate nanostructure.
AB  - We report the template-free, low-temperature synthesis of a stable, amorphous,
      and anhydrous magnesium carbonate nanostructure with pore sizes below 6 nm and a
      specific surface area of ~ 800 m(2) g(-1), substantially surpassing the surface
      area of all previously described alkali earth metal carbonates. The moisture
      sorption of the novel nanostructure is featured by a unique set of properties
      including an adsorption capacity ~50% larger than that of the hygroscopic zeolite
      Y at low relative humidities and with the ability to retain more than 75% of the
      adsorbed water when the humidity is decreased from 95% to 5% at room temperature.
      These properties can be regenerated by heat treatment at temperatures below 100
      degrees C.The structure is foreseen to become useful in applications such as
      humidity control, as industrial adsorbents and filters, in drug delivery and
      catalysis. 

PMID- 23874643
TI  - One small step for rhinos, one giant leap for wildlife management--imaging
      diagnosis of bone pathology in distal limb.
AB  - Chronic foot disease poses a threat to the general health, represents a
      tremendous clinical challenge, and often is a reason for euthanasia in captive
      megaherbivores, among them the elephant and rhinoceros. Nevertheless, apart from
      the elephant, foot pathology is handled as being confined only to soft tissues
      whereas bone pathology is often overlooked. As a case in point, the authors
      selected the second largest mammal on land, the rhinoceros. We performed a
      computed tomographic (CT) study using the highest resolution available in
      veterinary world, followed by digital radiography of eight distal limbs from two
      white and one Indian rhinoceroses. Our study demonstrated that bone pathology in
      rhinoceroses' foot is present and in large numbers, yet none of these were
      diagnosed ante mortem. Even when the animals were euthanized due to foot
      problems, the decision was based on soft tissue pathology rather than orthopedic
      reasons. Even more worrying is the fact that the largest number of
      osteopathologies was present in one of the white rhinoceroses that showed no
      discernable related clinical signs. This study describes for the first time the
      existence of bone pathology in white rhinoceros foot, in addition to the two
      previously described rhinoceros species--Indian and black rhinoceroses.
      Furthermore, the chronic foot disease reported for the Indian rhinoceros in our
      study was not restricted to soft tissue structures as was presumed ante mortem
      but included severe bone pathology. New evidence suggesting that osteopathology
      in rhinoceroses' distal limb is more widespread than it was thought before could
      force us to rethink of radiographic diagnosis in captive megaherbivores as
      routine examination incorporated into their health management. The anticipated
      improvements in radiologic examinations in megaherbivores will increase the
      effectiveness of their management and husbandry and open the way for improved
      animal welfare and better wildlife conservation.

PMID- 23874642
TI  - Characterization of the mitochondrial localization of the nuclear receptor SHP
      and regulation of its subcellular distribution by interaction with Bcl2 and
      HNF4alpha.
AB  - The nuclear receptor small heterodimer partner SHP was shown recently to
      translocate to the mitochondria, interact with Bcl2, and induce apoptosis in
      liver cancer cells. However, the exact mitochondrial localization of SHP remains
      to be determined. In addition, the detailed interaction domains between SHP and
      Bcl2 have not been characterized. Using biochemistry and molecular biology
      approaches, we demonstrate that SHP is localized to the mitochondrial outer
      membrane. Interestingly, compared with the full-length SHP, the N-terminal
      deleted protein exhibits increased expression in the mitochondria and decreased
      expression in the nucleus. GST pull-down assays demonstrate that the interaction
      domain of SHP shows the strongest interaction with Bcl2. Furthermore, the
      interaction of Bcl2 with SHP is completely abolished by deletion of the Bcl2
      transmembrane domain (TM), whereas deletion of the Bcl2 BH1 domain enhances the
      interaction. As expected, AHPN, a synthetic SHP ligand, markedly augments the
      direct protein-protein interaction between Bcl2 and SHP. Ectopic expression of
      hepatocyte nuclear factor 4 alpha (HNF4alpha) results in exclusive nuclear
      translocation of SHP proteins that contain either the full-length or the N
      terminal domain, but has a minimal effect on the subcellular distribution of SHP
      protein containing only the interaction domain or repression domain. These
      results indicate that the N-terminal domain of SHP is important for its nuclear
      translocation via HNF4alpha. Overall, this study provides novel insights into the
      domains of SHP that are critical for its shutting between different subcellular
      compartments.

PMID- 23874641
TI  - Comparison of oxidative stress/DNA damage in semen and blood of fertile and
      infertile men.
AB  - Abnormal spermatozoa frequently display typical features of oxidative stress,
      i.e. excessive level of reactive oxygen species (ROS) and depleted antioxidant
      capacity. Moreover, it has been found that a high level of oxidatively damaged
      DNA is associated with abnormal spermatozoa and male infertility. Therefore, the
      aim of our study was the comparison of oxidative stress/DNA damage in semen and
      blood of fertile and infertile men. The broad range of parameters which describe
      oxidative stress and oxidatively damaged DNA and repair were analyzed in the
      blood plasma and seminal plasma of groups of fertile and infertile subjects.
      These parameters include: (i) 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8
      oxo-7,8-dihydroguanine (8-oxoGua) levels in urine; (ii) 8-oxodG level in DNA
      isolated from leukocytes and spermatozoa; (iii) antioxidant vitamins (A, C and E)
      and uric acid. Urinary excretion of 8-oxodG and 8-oxoGua and the level of
      oxidatively damaged DNA in leukocytes as well as the level of antioxidant
      vitamins were analyzed using HPLC and HPLC/GC/MS methods. The results of our
      study demonstrate that 8-oxodG level significantly correlated with every
      parameter which describe sperm quality: sperm count, motility and morphology.
      Moreover, the data indicate a higher level of 8-oxodG in sperm DNA compared with
      DNA of surrogate tissue (leukocytes) in infertile men as well as in healthy
      control group. For the whole study population the median values of 8-oxodG/10(6)
      dG were respectively 7.85 and 5.87 (p=0.000000002). Since 8-oxodG level in sperm
      DNA is inversely correlated with urinary excretion rate of 8-oxoGua, which is the
      product of OGG1 activity, we hypothesize that integrity of spermatozoa DNA may be
      highly dependent on OGG1 activity. No relationship between the whole body
      oxidative stress and that of sperm plasma was found, which suggests that the
      redox status of semen may be rather independent on this characteristic for other
      tissues.

PMID- 23874644
TI  - Association of knowledge of HIV and other factors with individuals' attitudes
      toward HIV infection: a national cross-sectional survey among the Japanese non
      medical working population.
AB  - BACKGROUND: The stigma of and discrimination because of HIV has been described as
      the most important obstacle to prevention and treatment efforts. The purpose of
      this study was to investigate negative attitudes and prejudice toward HIV among
      the Japanese non-medical working population and to explore contributing factors.
      METHODS: An online anonymous nationwide survey involving approximately 3,000
      individuals was conducted in Japan. Questions ranged from background information
      and HIV knowledge to individuals' attitudes towards HIV infection in the
      workplace. Descriptive statistics and logistic regression were applied for
      analysis. RESULTS: Thirty-three percent of participants feared transmission of
      HIV from infected colleagues, 34% tended to avoid contact with them and 40% had
      prejudiced opinions about HIV infection. Despite a relatively high level of
      knowledge of HIV/AIDS overall (11.9 +/- 3.3 from 15 points), only 50% of
      individuals were aware of some issues. Greater knowledge was associated with less
      negative attitudes towards HIV infection (OR 0.39, 95% CI 0.31-0.48 for
      prejudiced opinion, high compared with low level of knowledge), whereas greater
      health consciousness was inversely related to attitude (OR 1.97, 95% CI 1.50-2.58
      for prejudiced opinion, high compared with low health consciousness). CONCLUSION:
      Knowledge neutralizes peoples' negative attitudes towards HIV infection, whereas
      greater health consciousness may worsen them. Educational programs should balance
      knowledge with health consciousness to improve the efficacy of HIV interventions.

PMID- 23874645
TI  - An evaluation of the accuracy and performance of lightweight GPS collars in a
      suburban environment.
AB  - The recent development of lightweight GPS collars has enabled medium-to-small
      sized animals to be tracked via GPS telemetry. Evaluation of the performance and
      accuracy of GPS collars is largely confined to devices designed for large animals
      for deployment in natural environments. This study aimed to assess the
      performance of lightweight GPS collars within a suburban environment, which may
      be different from natural environments in a way that is relevant to satellite
      signal acquisition. We assessed the effects of vegetation complexity, sky
      availability (percentage of clear sky not obstructed by natural or artificial
      features of the environment), proximity to buildings, and satellite geometry on
      fix success rate (FSR) and location error (LE) for lightweight GPS collars within
      a suburban environment. Sky availability had the largest affect on FSR, while LE
      was influenced by sky availability, vegetation complexity, and HDOP (Horizontal
      Dilution of Precision). Despite the complexity and modified nature of suburban
      areas, values for FSR (mean= 90.6%) and LE (mean = 30.1 m) obtained within the
      suburban environment are comparable to those from previous evaluations of GPS
      collars designed for larger animals and within less built-up environments. Due to
      fine-scale patchiness of habitat within urban environments, it is recommended
      that resource selection methods that are not reliant on buffer sizes be utilised
      for selection studies.

PMID- 23874646
TI  - Particle size of latex beads dictates IL-1beta production mechanism.
AB  - Macrophages (Mphi) are well documented to produce IL-1beta through various
      signaling pathways in response to small particles such as silica, asbestos and
      urea crystals, in the presence of lipopolysaccharide (LPS). However, it has not
      been clear to what extent particle size affects the response. To investigate this
      point, we stimulated bone marrow-derived macrophages (BMDM) with size-defined
      latex beads (LxB). Although both nano-sized (20 nm) and micro-sized (1,000 nm)
      LxB induced IL-1beta production, only the nano-sized particles formed large
      intracellular vacuoles. In contrast, 100 nm LxB did not induce either of the
      responses. The same cellular responses were also observed in primary microglia
      cells. Although K(+) efflux and NLRP3 activation in BMDM were crucial in response
      to both 20 and 1,000 nm LxB, only IL-1beta production by 20 nm LxB was sensitive
      to cathepsin B and P2X7, a receptor for ATP. The response by 1,000 nm LxB relied
      on a robust production of reactive oxygen species (ROS), since IL-1beta
      production was remarkably reduced by ROS inhibitors such as diphenylene iodonium
      (DPI) and N-acetylcysteine (NAC). In contrast, IL-1beta production by 20 nm LxB
      was augmented by NAC and in BMDM deficient in thioredoxin-binding protein-2 (TBP
      2), a negative regulator of the ROS scavenger thioredoxin. These results suggest
      that the cells responded differently in their secretion of IL-1beta depending on
      particle size, and that there is a range within which neither pathway works. 

PMID- 23874647
TI  - Multi-QTL mapping for quantitative traits using epistatic distorted markers.
AB  - The interaction between segregation distortion loci (SDL) has been often observed
      in all kinds of mapping populations. However, little has been known about the
      effect of epistatic SDL on quantitative trait locus (QTL) mapping. Here we
      proposed a multi-QTL mapping approach using epistatic distorted markers. Using
      the corrected linkage groups, epistatic SDL was identified. Then, these SDL
      parameters were used to correct the conditional probabilities of QTL genotypes,
      and these corrections were further incorporated into the new QTL mapping
      approach. Finally, a set of simulated datasets and a real data in 304 mouse F2
      individuals were used to validate the new method. As compared with the old
      method, the new one corrects genetic distance between distorted markers, and
      considers epistasis between two linked SDL. As a result, the power in the
      detection of QTL is higher for the new method than for the old one, and
      significant differences for estimates of QTL parameters between the two methods
      were observed, except for QTL position. Among two QTL for mouse weight, one
      significant difference for QTL additive effect between the above two methods was
      observed, because epistatic SDL between markers C66 and T93 exists (P = 2.94e-4).

PMID- 23874648
TI  - European invasion of North American Pinus strobus at large and fine scales: high
      genetic diversity and fine-scale genetic clustering over time in the adventive
      range.
AB  - BACKGROUND: North American Pinus strobus is a highly invasive tree species in
      Central Europe. Using ten polymorphic microsatellite loci we compared various
      aspects of the large-scale genetic diversity of individuals from 30 sites in the
      native distribution range with those from 30 sites in the European adventive
      distribution range. To investigate the ascertained pattern of genetic diversity
      of this intercontinental comparison further, we surveyed fine-scale genetic
      diversity patterns and changes over time within four highly invasive populations
      in the adventive range. RESULTS: Our data show that at the large scale the
      genetic diversity found within the relatively small adventive range in Central
      Europe, surprisingly, equals the diversity found within the sampled area in the
      native range, which is about thirty times larger. Bayesian assignment grouped
      individuals into two genetic clusters separating North American native
      populations from the European, non-native populations, without any strong genetic
      structure shown over either range. In the case of the fine scale, our comparison
      of genetic diversity parameters among the localities and age classes yielded no
      evidence of genetic diversity increase over time. We found that SGS differed
      across age classes within the populations under study. Old trees in general
      completely lacked any SGS, which increased over time and reached its maximum in
      the sapling stage. CONCLUSIONS: Based on (1) the absence of difference in genetic
      diversity between the native and adventive ranges, together with the lack of
      structure in the native range, and (2) the lack of any evidence of any temporal
      increase in genetic diversity at four highly invasive populations in the
      adventive range, we conclude that population amalgamation probably first happened
      in the native range, prior to introduction. In such case, there would have been
      no need for multiple introductions from previously isolated populations, but only
      several introductions from genetically diverse populations.

PMID- 23874649
TI  - Single-row or double-row fixation technique for full-thickness rotator cuff
      tears: a meta-analysis.
AB  - BACKGROUND: The single-row and double-row fixation techniques have been widely
      used for rotator cuff tears. However, whether the double-row technique produces
      superior clinical or anatomic outcomes is still considered controversial. This
      study aims to use meta-analysis to compare the clinical and anatomical outcomes
      between the two techniques. METHODS: The Pubmed, Embase, and Cochrane library
      databases were searched for relevant studies published before November 1, 2012.
      Studies clearly reporting a comparison of the single-row and double-row
      techniques were selected. The Constant, ASES, and UCLA scale systems and the
      rotator cuff integrity rate were evaluated. The weighted mean differences and
      relative risks were calculated using a fixed-effects or random-effects model.
      RESULTS: Eight studies were included in this meta-analysis. The weighted mean
      differences of the ASES (-0.84; P = 0.04; I(2) = 0%) and UCLA (-0.75; P = 0.007;
      I(2) = 0%) scales were significantly low in the single-row group for full
      thickness rotator cuff tears. For tear sizes smaller than 3 cm, no significant
      difference was found between the groups no matter in Constant (P = 0.95; I(2) =
      0%), ASES (P = 0.77; I(2) = 0%), or UCLA (P = 0.24; I(2) = 13%) scales. For tear
      sizes larger than 3 cm, the ASES (-1.95; P = 0.001; I(2) = 49%) and UCLA (-1.17;
      P = 0.006; I(2) = 0%) scales were markedly lower in the single-row group. The
      integrity of the rotator cuff (0.81; P = 0.0004; I(2) = 10%) was greater and the
      partial thickness retear rate (1.93; P = 0.007; I(2) = 10%) was less in the
      double-row group. Full-thickness retears showed no difference between the groups
      (P = 0.15; I(2) = 0%). CONCLUSION: The meta-analysis suggests that the double-row
      fixation technique increases post-operative rotator cuff integrity and improves
      the clinical outcomes, especially for full-thickness rotator cuff tears larger
      than 3 cm. For tear sizes smaller than 3 cm, there was no difference in the
      clinical outcomes between the two techniques. LEVEL OF EVIDENCE: Level I.

PMID- 23874650
TI  - Single point mutations result in the miss-sorting of Glut4 to a novel membrane
      compartment associated with stress granule proteins.
AB  - Insulin increases cellular glucose uptake and metabolism in the postprandial
      state by acutely stimulating the translocation of the Glut4 glucose transporter
      from intracellular membrane compartments to the cell surface in muscle and fat
      cells. The intracellular targeting of Glut4 is dictated by specific structural
      motifs within cytoplasmic domains of the transporter. We demonstrate that two
      leucine residues at the extreme C-terminus of Glut4 are critical components of a
      motif (IRM, insulin responsive motif) involved in the sorting of the transporter
      to insulin responsive vesicles in 3T3L1 adipocytes. Light microscopy, immunogold
      electron microscopy, subcellular fractionation, and sedimentation analysis
      indicate that mutations in the IRM cause the aberrant targeting of Glut4 to large
      dispersed membrane vesicles that are not insulin responsive. Proteomic
      characterization of rapidly and slowly sedimenting membrane vesicles (RSVs and
      SSVs) that were highly enriched by immunoadsorption for either wild-type Glut4 or
      an IRM mutant revealed that the major vesicle fraction containing the mutant
      transporter (IRM-RSVs) possessed a relatively small and highly distinct protein
      population that was enriched for proteins associated with stress granules. We
      suggest that the IRM is critical for an early step in the sorting of Glut4 to
      insulin-responsive subcellular membrane compartments and that IRM mutants are
      miss-targeted to relatively large, amorphous membrane vesicles that may be
      involved in a degradation pathway for miss-targeted or miss-folded proteins or
      represent a transitional membrane compartment that Glut4 traverses en route to
      insulin responsive storage compartments. 

PMID- 23874651
TI  - RNA deep sequencing analysis reveals that nicotine restores impaired gene
      expression by viral proteins in the brains of HIV-1 transgenic rats.
AB  - Persons infected with HIV-1 often develop neurologic disorders despite receiving
      highly active anti-retroviral therapy. Although the underlying mechanism is
      largely undetermined, our previous RNA-seq-based study showed that the expression
      of many genes was altered in the central nervous system (CNS) of HIV-1 transgenic
      (HIV-1Tg) rats. Because nicotine, a natural agonist of nicotinic acetylcholine
      receptors, exhibits a neuroprotective effect, we presently tested the hypothesis
      that nicotine restores the expression of altered genes in the CNS of HIV-1Tg
      rats. Adult male HIV-1Tg and F344 control strain rats were injected with either
      nicotine (0.25 mg/kg) or saline subcutaneously twice a day for 17 days. Gene
      expression in the prefrontal cortex (PFC), dorsal hippocampus (HIP), and dorsal
      striatum (STR) was evaluated using the RNA deep sequencing technique. We found
      that about 20% of the altered genes in the HIV-1Tg rat were affected by nicotine
      in each brain region, with the expression of most restored. Analysis of the
      restored genes showed distinct pathways corrected by nicotine in different brain
      regions of HIV-1Tg rats. Specifically, the two most significantly restored
      pathways were Wnt/beta-catenin signaling and ephrin B signaling in the PFC, cAMP
      responsive element-binding protein (CREB) signaling and glutathione metabolism
      pathway in the HIP, and tricarboxylic acid (TCA) cycle and calcium signaling in
      the STR. Together, our findings indicate that cholinergic modulators such as
      nicotine have beneficial effects on HIV-1-induced neurologic deficits. 

PMID- 23874652
TI  - Systemic lupus erythematosus patients contain significantly less igm against mono
      methylated lysine than healthy subjects.
AB  - Post-translational modifications on proteins are important in biological
      processes but may create neo-epitopes that induce autoimmune responses. In this
      study, we measured the serum IgG and IgM response to a set of non-modified or
      acetyl- and methyl-modified peptides corresponding to residues 1-19 of the
      histone 3 N-terminal tail in systemic lupus erythematosus (SLE) patients and
      healthy subjects. Our results indicated that the SLE patients and healthy
      subjects produced antibodies (Abs) to the peptides, but the two groups had
      different Ab isotype and epitope preferences. Abs to the non-modified form, H31
      19, were of the IgG isotype and produced by SLE patients. They could not
      recognize the scrambled H31-19, which contained the same amino acid composition
      but a different sequence as H31-19. In comparison, healthy subjects in general
      did not produce IgG against H31-19. However, about 70% of the healthy subjects
      produced IgM Abs against mono-methylated K9 of H31-19 (H31-19K9me). Our further
      studies revealed that epsilon-amine mono-methylated lysine could completely
      inhibit the IgM binding to H31-19K9me, but lysine had no inhibitory effect. In
      addition, the IgM Abs could bind peptides containing a mono-methylated lysine
      residue but with totally different sequences. Thus, mono-methylated lysine was
      the sole epitope for the IgM. Interestingly, SLE patients had much lower levels
      of this type of IgM. There was no obvious correlation between the IgM levels and
      disease activity and the decreased IgM was unlikely caused by medical
      treatments.We also found that the IgM Abs were not polyreactive to dsDNA, ssDNA,
      lipopolysaccharide (LPS) or insulin and they did not exist in umbilical cord
      serum, implying that they were not natural Abs. The IgM Abs against mono
      methylated lysine are present in healthy subjects but are significantly lower in
      SLE patients, suggesting a distinct origin of production and special
      physiological functions. 

PMID- 23874653
TI  - A high diversity of Eurasian lineage low pathogenicity avian influenza A viruses
      circulate among wild birds sampled in Egypt.
AB  - Surveillance for influenza A viruses in wild birds has increased substantially as
      part of efforts to control the global movement of highly pathogenic avian
      influenza A (H5N1) virus. Studies conducted in Egypt from 2003 to 2007 to monitor
      birds for H5N1 identified multiple subtypes of low pathogenicity avian influenza
      A viruses isolated primarily from migratory waterfowl collected in the Nile
      Delta. Phylogenetic analysis of 28 viral genomes was performed to estimate their
      nearest ancestors and identify possible reassortants. Migratory flyway patterns
      were included in the analysis to assess gene flow between overlapping flyways.
      Overall, the viruses were most closely related to Eurasian, African and/or
      Central Asian lineage low pathogenicity viruses and belonged to 15 different
      subtypes. A subset of the internal genes seemed to originate from specific
      flyways (Black Sea-Mediterranean, East African-West Asian). The remaining genes
      were derived from a mixture of viruses broadly distributed across as many as 4
      different flyways suggesting the importance of the Nile Delta for virus
      dispersal. Molecular clock date estimates suggested that the time to the nearest
      common ancestor of all viruses analyzed ranged from 5 to 10 years, indicating
      frequent genetic exchange with viruses sampled elsewhere. The intersection of
      multiple migratory bird flyways and the resulting diversity of influenza virus
      gene lineages in the Nile Delta create conditions favoring reassortment, as
      evident from the gene constellations identified by this study. In conclusion, we
      present for the first time a comprehensive phylogenetic analysis of full genome
      sequences from low pathogenic avian influenza viruses circulating in Egypt,
      underscoring the significance of the region for viral reassortment and the
      potential emergence of novel avian influenza A viruses, as well as representing a
      highly diverse influenza A virus gene pool that merits continued monitoring. 

PMID- 23874654
TI  - Dynamic recruitment of CDK5RAP2 to centrosomes requires its association with
      dynein.
AB  - CDK5RAP2 is a centrosomal protein known to be involved in the regulation of the
      gamma-tubulin ring complex and thus the organization of microtubule arrays.
      However, the mechanism by which CDK5RAP2 is itself recruited to centrosomes is
      poorly understood. We report here that CDK5RAP2 displays highly dynamic
      attachment to centrosomes in a microtubule-dependent manner. CDK5RAP2 associates
      with the retrograde transporter dynein-dynactin and contains a sequence motif
      that binds to dynein light chain 8. Significantly, disruption of cellular dynein
      dynactin function reduces the centrosomal level of CDK5RAP2. These results reveal
      a key role of the dynein-dynactin complex in the dynamic recruitment of CDK5RAP2
      to centrosomes. 

PMID- 23874655
TI  - The anti-cancer property of proteins extracted from Gynura procumbens (Lour.)
      Merr.
AB  - Gynura procumbens (Lour.) Merr. belongs to the Asteraceae Family. The plant is a
      well-known traditional herb in South East Asia and it is widely used to treat
      inflammation, kidney discomfort, high cholesterol level, diabetic, cancer and
      high blood pressure. Our earlier study showed the presence of valuable plant
      defense proteins, such as peroxidase, thaumatin-like proteins and miraculin in
      the leaf of G. procumbens. However, the effects of these defense proteins on
      cancers have never been determined previously. In the present study, we
      investigated the bioactivity of gel filtration fractionated proteins of G.
      procumbens leaf extract. The active protein fraction, SN-F11/12, was found to
      inhibit the growth of a breast cancer cell line, MDA-MB-231, at an EC50 value of
      3.8 ug/mL. The mRNA expressions of proliferation markers, Ki67 and PCNA, were
      reduced significantly in the MDA-MB-23 cells treated with SN-F11/12. The
      expression of invasion marker, CCL2, was also found reduced in the treated MDA-MB
      231 cells. All these findings highlight the anti-cancer property of SN-F11/12,
      therefore, the proteins in this fraction can be a potential chemotherapeutic
      agent for breast cancer treatment. 

PMID- 23874656
TI  - Clinical and pathologic factors affecting lymph node yields in colorectal cancer.
AB  - OBJECTIVE: Lymph node yield is recommended as a benchmark of quality care in
      colorectal cancer. The objective of this study was to evaluate the impact of
      various factors upon lymph node yield and to identify independent factors
      associated with lymph node harvest. MATERIALS AND METHODS: The records of 162
      patients with Stage I to Stage III colorectal cancers seen in one institution
      were reviewed. These patients underwent radical surgery as definitive therapy;
      high-risk patients then received adjuvant treatment. Pathologic and demographic
      data were recorded and analyzed. The subgroup analysis of lymph node yields was
      determined using a t-test and analysis of variants. Linear regression model and
      multivariable analysis were used to perform potential confounding and predicting
      variables. RESULTS: Five variables had significant association with lymph node
      yield after adjustment for other factors in a multiple linear regression model.
      These variables were: tumor size, surgical method, specimen length, and
      individual surgeon and pathologist. The model with these five significant
      variables interpreted 44.4% of the variation. CONCLUSIONS: Patients, tumor
      characteristics and surgical variables all influence the number of lymph nodes
      retrieved. Physicians are the main gatekeepers. Adequate training and optimized
      guidelines could greatly improve the quality of lymph node yields.

PMID- 23874657
TI  - Bone marrow SSEA1+ cells support the myocardium in cardiac pressure overload.
AB  - RATIONALE: Stage specific embryonic antigen 1+ (SSEA1+) cells have been described
      as the most primitive mesenchymal progenitor cell in the bone marrow. Cardiac
      injury mobilizes SSEA1+ cells into the peripheral blood but their in vivo
      function has not been characterized. OBJECTIVE: We generated animals with
      chimeric bone marrow to determine the fate and function of bone marrow SSEA1+
      cells in response to acute cardiac pressure overload. METHODS AND RESULTS:
      Lethally irradiated mice were transplanted with normal bone marrow where the wild
      type SSEA1+ cells were replaced with green fluorescent protein (GFP) SSEA1+
      cells. Cardiac injury was induced by trans-aortic constriction (TAC). We
      identified significant GFP+ cell engraftment into the myocardium after TAC. Bone
      marrow GFP+ SSEA1 derived cells acquired markers of endothelial lineage, but did
      not express markers of c-kit+ cardiac progenitor cells. The function of bone
      marrow SSEA1+ cells after TAC was determined by transplanting lethally irradiated
      mice with bone marrow depleted of SSEA1+ cells (SSEA1-BM). The cardiac function
      of SSEA1-BM mice declined at a greater rate after TAC compared to their complete
      bone marrow transplant counterparts and was associated with decreased bone marrow
      cell engraftment and greater vessel rarefication in the myocardium. CONCLUSIONS:
      These results provide evidence for the recruitment of endogenous bone marrow
      SSEA1+ cells to the myocardium after TAC. We demonstrate that, in vivo, bone
      marrow SSEA1+ cells have the differentiation potential to acquire endothelial
      lineage markers. We also show that bone marrow SSEA1+ deficiency is associated
      with a reduced compensatory capacity to cardiac pressure overload, suggesting
      their importance in cardiac homeostasis. These data demonstrate that bone marrow
      SSEA1+ cells are critical for sustaining vascular density and cardiac repair to
      pressure overload.

PMID- 23874658
TI  - MutMap+: genetic mapping and mutant identification without crossing in rice.
AB  - Advances in genome sequencing technologies have enabled researchers and breeders
      to rapidly associate phenotypic variation to genome sequence differences. We
      recently took advantage of next-generation sequencing technology to develop
      MutMap, a method that allows rapid identification of causal nucleotide changes of
      rice mutants by whole genome resequencing of pooled DNA of mutant F2 progeny
      derived from crosses made between candidate mutants and the parental line. Here
      we describe MutMap+, a versatile extension of MutMap, that identifies causal
      mutations by comparing SNP frequencies of bulked DNA of mutant and wild-type
      progeny of M3 generation derived from selfing of an M2 heterozygous individual.
      Notably, MutMap+ does not necessitate artificial crossing between mutants and the
      wild-type parental line. This method is therefore suitable for identifying
      mutations that cause early development lethality, sterility, or generally hamper
      crossing. Furthermore, MutMap+ is potentially useful for gene isolation in crops
      that are recalcitrant to artificial crosses. 

PMID- 23874659
TI  - Is it possible to improve memory function by upregulation of the cholesterol 24S
      hydroxylase (CYP46A1) in the brain?
AB  - We previously described a heterozygous mouse model overexpressing human HA-tagged
      24S-hydroxylase (CYP46A1) utilizing a ubiquitous expression vector. In this
      study, we generated homozygotes of these mice with circulating levels of 24OH 30
      60% higher than the heterozygotes. Female homozygous CYP46A1 transgenic mice,
      aged 15 months, showed an improvement in spatial memory in the Morris water maze
      test as compared to the wild type mice. The levels of N-Methyl-D-Aspartate
      receptor 1, phosphorylated-N-Methyl-D-Aspartate receptor 2A, postsynaptic density
      95, synapsin-1 and synapthophysin were significantly increased in the hippocampus
      of the CYP46A1 transgenic mice as compared to the controls. The levels of
      lanosterol in the brain of the CYP46A1 transgenic mice were significantly
      increased, consistent with a higher synthesis of cholesterol. Our results are
      discussed in relation to the hypothesis that the flux in the mevalonate pathway
      in the brain is of importance in cognitive functions. 

PMID- 23874661
TI  - Enlarge the training set based on inter-class relationship for face recognition
      from one image per person.
AB  - In some large-scale face recognition task, such as driver license identification
      and law enforcement, the training set only contains one image per person. This
      situation is referred to as one sample problem. Because many face recognition
      techniques implicitly assume that several (at least two) images per person are
      available for training, they cannot deal with the one sample problem. This paper
      investigates principal component analysis (PCA), Fisher linear discriminant
      analysis (LDA), and locality preserving projections (LPP) and shows why they
      cannot perform well in one sample problem. After that, this paper presents four
      reasons that make one sample problem itself difficult: the small sample size
      problem; the lack of representative samples; the underestimated intra-class
      variation; and the overestimated inter-class variation. Based on the analysis,
      this paper proposes to enlarge the training set based on the inter-class
      relationship. This paper also extends LDA and LPP to extract features from the
      enlarged training set. The experimental results show the effectiveness of the
      proposed method. 

PMID- 23874660
TI  - A DNA 'barcode blitz': rapid digitization and sequencing of a natural history
      collection.
AB  - DNA barcoding protocols require the linkage of each sequence record to a voucher
      specimen that has, whenever possible, been authoritatively identified. Natural
      history collections would seem an ideal resource for barcode library
      construction, but they have never seen large-scale analysis because of concerns
      linked to DNA degradation. The present study examines the strength of this
      barrier, carrying out a comprehensive analysis of moth and butterfly
      (Lepidoptera) species in the Australian National Insect Collection. Protocols
      were developed that enabled tissue samples, specimen data, and images to be
      assembled rapidly. Using these methods, a five-person team processed 41,650
      specimens representing 12,699 species in 14 weeks. Subsequent molecular analysis
      took about six months, reflecting the need for multiple rounds of PCR as sequence
      recovery was impacted by age, body size, and collection protocols. Despite these
      variables and the fact that specimens averaged 30.4 years old, barcode records
      were obtained from 86% of the species. In fact, one or more barcode compliant
      sequences (>487 bp) were recovered from virtually all species represented by five
      or more individuals, even when the youngest was 50 years old. By assembling
      specimen images, distributional data, and DNA barcode sequences on a web
      accessible informatics platform, this study has greatly advanced accessibility to
      information on thousands of species. Moreover, much of the specimen data became
      publically accessible within days of its acquisition, while most sequence results
      saw release within three months. As such, this study reveals the speed with which
      DNA barcode workflows can mobilize biodiversity data, often providing the first
      web-accessible information for a species. These results further suggest that
      existing collections can enable the rapid development of a comprehensive DNA
      barcode library for the most diverse compartment of terrestrial biodiversity -
      insects. 

PMID- 23874662
TI  - Molecular cloning and characterization of juvenile hormone acid methyltransferase
      in the honey bee, Apis mellifera, and its differential expression during caste
      differentiation.
AB  - Juvenile hormone acid methyltransferase (JHAMT) is an enzyme involved in one of
      the final steps of juvenile hormone biosynthesis in insects. It transfers a
      methyl group from S-adenosyl-L-methionine (SAM) to the carboxyl group of either
      farnesoic acid (FA) or JH acid (JHA). Several genes coding for JHAMT have been
      cloned and characterized from insects from different orders, and they have been
      shown to play critical roles in metamorphosis and reproduction. However, the
      significance of JHAMT in Hymenopteran insects is unknown. We used RACE
      amplification method to clone JHAMT cDNA from the honey bee, Apis mellifera
      (AmJHAMT). The full length cDNA of AmJHAMT that we cloned is 1253bp long and
      encodes a 278-aa protein that shares 32-36% identity with known JHAMTs. A SAM
      binding motif, conserved in the SAM-dependent methyltransferase (SAM-MT)
      superfamily, is present in AmJHAMT. Its secondary structure also contains a
      typical SAM-MT fold. Most of the active sites bound with SAM and substrates (JHA
      or FA) are conserved in AmJHAMT as in other JHAMT orthologs. Phylogenetic
      analysis clustered AmJHAMT with the other orthologs from Hymenoptera to form a
      major clade in the phylogenetic tree. Purified recombinant AmJHAMT protein
      expressed in E. coli was used to produce polyclonal antibodies and to verify the
      identity of AmJHAMT by immunoblotting and mass spectrometry. Quantitative RT-PCR
      and immunoblotting analyses revealed that queen larvae contained significantly
      higher levels of AmJHAMT mRNA and protein than worker larvae during the periods
      of caste development. The temporal profiles of both AmJHAMT mRNA and protein in
      queens and workers showed a similar pattern as the JH biosynthesis. These results
      suggest that the gene that we cloned codes for a functional JHAMT that catalyzes
      the final reactions of JH biosynthesis in honey bees. In addition, AmJHAMT may
      play an important role in honey bee caste differentiation. 

PMID- 23874663
TI  - Discovery and characterization of BlsE, a radical S-adenosyl-L-methionine
      decarboxylase involved in the blasticidin S biosynthetic pathway.
AB  - BlsE, a predicted radical S-adenosyl-L-methionine (SAM) protein, was
      anaerobically purified and reconstituted in vitro to study its function in the
      blasticidin S biosynthetic pathway. The putative role of BlsE was elucidated
      based on bioinformatics analysis, genetic inactivation and biochemical
      characterization. Biochemical results showed that BlsE is a SAM-dependent radical
      enzyme that utilizes cytosylglucuronic acid, the accumulated intermediate
      metabolite in blsE mutant, as substrate and catalyzes decarboxylation at the C5
      position of the glucoside residue to yield cytosylarabinopyranose. Additionally,
      we report the purification and reconstitution of BlsE, characterization of its
      [4Fe-4S] cluster using UV-vis and electron paramagnetic resonance (EPR)
      spectroscopic analysis, and investigation of the ability of flavodoxin (Fld),
      flavodoxin reductase (Fpr) and NADPH to reduce the [4Fe-4S](2+) cluster.
      Mutagenesis studies demonstrated that Cys31, Cys35, Cys38 in the C***C*MC motif
      and Gly73, Gly74, Glu75, Pro76 in the GGEP motif were crucial amino acids for
      BlsE activity while mutation of Met37 had little effect on its function. Our
      results indicate that BlsE represents a typical [4Fe-4S]-containing radical SAM
      enzyme and it catalyzes decarboxylation in blasticidin S biosynthesis. 

PMID- 23874664
TI  - Interrogating transcriptional regulatory sequences in Tol2-mediated Xenopus
      transgenics.
AB  - Identifying gene regulatory elements and their target genes in vertebrates
      remains a significant challenge. It is now recognized that transcriptional
      regulatory sequences are critical in orchestrating dynamic controls of tissue
      specific gene expression during vertebrate development and in adult tissues, and
      that these elements can be positioned at great distances in relation to the
      promoters of the genes they control. While significant progress has been made in
      mapping DNA binding regions by combining chromatin immunoprecipitation and next
      generation sequencing, functional validation remains a limiting step in improving
      our ability to correlate in silico predictions with biological function. We
      recently developed a computational method that synergistically combines genome
      wide gene-expression profiling, vertebrate genome comparisons, and transcription
      factor binding-site analysis to predict tissue-specific enhancers in the human
      genome. We applied this method to 270 genes highly expressed in skeletal muscle
      and predicted 190 putative cis-regulatory modules. Furthermore, we optimized Tol2
      transgenic constructs in Xenopus laevis to interrogate 20 of these elements for
      their ability to function as skeletal muscle-specific transcriptional enhancers
      during embryonic development. We found 45% of these elements expressed only in
      the fast muscle fibers that are oriented in highly organized chevrons in the
      Xenopus laevis tadpole. Transcription factor binding site analysis identified >2
      Mef2/MyoD sites within ~200 bp regions in 6 of the validated enhancers, and
      systematic mutagenesis of these sites revealed that they are critical for the
      enhancer function. The data described herein introduces a new reporter system
      suitable for interrogating tissue-specific cis-regulatory elements which allows
      monitoring of enhancer activity in real time, throughout early stages of
      embryonic development, in Xenopus.

PMID- 23874665
TI  - Msl2 is a novel component of the vertebrate DNA damage response.
AB  - hMSL2 (male-specific lethal 2, human) is a RING finger protein with ubiquitin
      ligase activity. Although it has been shown to target histone H2B at lysine 34
      and p53 at lysine 351, suggesting roles in transcription regulation and
      apoptosis, its function in these and other processes remains poorly defined. To
      further characterize this protein, we have disrupted the Msl2 gene in chicken
      DT40 cells. Msl2(-/-) cells are viable, with minor growth defects. Biochemical
      analysis of the chromatin in these cells revealed aberrations in the levels of
      several histone modifications involved in DNA damage response pathways. DNA
      repair assays show that both Msl2(-/-) chicken cells and hMSL2-depleted human
      cells have defects in non-homologous end joining (NHEJ) repair. DNA damage assays
      also demonstrate that both Msl2 and hMSL2 proteins are modified and stabilized
      shortly after induction of DNA damage. Moreover, hMSL2 mediates modification,
      presumably ubiquitylation, of a key DNA repair mediator 53BP1 at lysine 1690.
      Similarly, hMSL1 and hMOF (males absent on the first) are modified in the
      presence of hMSL2 shortly after DNA damage. These data identify a novel role for
      Msl2/hMSL2 in the cellular response to DNA damage. The kinetics of its
      stabilization suggests a function early in the NHEJ repair pathway. Moreover,
      Msl2 plays a role in maintaining normal histone modification profiles, which may
      also contribute to the DNA damage response. 

PMID- 23874666
TI  - A systems-genetics approach and data mining tool to assist in the discovery of
      genes underlying complex traits in Oryza sativa.
AB  - Many traits of biological and agronomic significance in plants are controlled in
      a complex manner where multiple genes and environmental signals affect the
      expression of the phenotype. In Oryza sativa (rice), thousands of quantitative
      genetic signals have been mapped to the rice genome. In parallel, thousands of
      gene expression profiles have been generated across many experimental conditions.
      Through the discovery of networks with real gene co-expression relationships, it
      is possible to identify co-localized genetic and gene expression signals that
      implicate complex genotype-phenotype relationships. In this work, we used a
      knowledge-independent, systems genetics approach, to discover a high-quality set
      of co-expression networks, termed Gene Interaction Layers (GILs). Twenty-two GILs
      were constructed from 1,306 Affymetrix microarray rice expression profiles that
      were pre-clustered to allow for improved capture of gene co-expression
      relationships. Functional genomic and genetic data, including over 8,000 QTLs and
      766 phenotype-tagged SNPs (p-value < = 0.001) from genome-wide association
      studies, both covering over 230 different rice traits were integrated with the
      GILs. An online systems genetics data-mining resource, the GeneNet Engine, was
      constructed to enable dynamic discovery of gene sets (i.e. network modules) that
      overlap with genetic traits. GeneNet Engine does not provide the exact set of
      genes underlying a given complex trait, but through the evidence of gene-marker
      correspondence, co-expression, and functional enrichment, site visitors can
      identify genes with potential shared causality for a trait which could then be
      used for experimental validation. A set of 2 million SNPs was incorporated into
      the database and serve as a potential set of testable biomarkers for genes in
      modules that overlap with genetic traits. Herein, we describe two modules found
      using GeneNet Engine, one with significant overlap with the trait amylose content
      and another with significant overlap with blast disease resistance.

PMID- 23874667
TI  - Assessment of the magnitude of contextual and individual demographic effects on
      diabetes mellitus and glucose intolerance in rural Southwest China: a multilevel
      analysis.
AB  - OBJECTIVE: This study aimed to determine the contribution of individual and
      contextual socioeconomic status (SES) to the prevalence of diabetes mellitus and
      glucose intolerance in the adult population in rural southwest China. METHODS: A
      population-based cross-sectional study of diabetes was performed in 4801(2152
      men) Chinese adults (>= 25 years old). Multilevel logistic regression model was
      used to examine the association between individuals' and townships' variables and
      the prevalence of diabetes mellitus and glucose intolerance. RESULTS: The age-and
      gender-standardized prevalence of diabetes mellitus and glucose intolerance were
      7.1% (3.6% for undiagnosed) and 8.8% in adults aged >= 25 years, respectively,
      and increasing with age. Females were more likely to develop diabetes than males.
      The probability of developing diabetes increased with BMI. Both contextual and
      individual educational level and yearly household income were found to be
      negatively associated with the prevalence of diabetes. Residence in communities
      with a higher percentage of ethnic minorities was associated with higher
      prevalence of diabetes. Smoking had a protective effect for diabetes, drinking
      had a positive association with diabetes mellitus and glucose intolerance.
      CONCLUSIONS: Diabetes mellitus and glucose intolerance are common in rural adults
      of southwest China by international standards. These results indicate that
      diabetes mellitus has become a major public health problem in rural areas in
      southwest China, and strategies aimed at the prevention and treatment of diabetes
      mellitus and glucose intolerance are needed.

PMID- 23874668
TI  - The influence of environmental variables on the presence of white sharks,
      Carcharodon carcharias at two popular Cape Town bathing beaches: a generalized
      additive mixed model.
AB  - Shark attacks on humans are high profile events which can significantly influence
      policies related to the coastal zone. A shark warning system in South Africa,
      Shark Spotters, recorded 378 white shark (Carcharodon carcharias) sightings at
      two popular beaches, Fish Hoek and Muizenberg, during 3690 six-hour long spotting
      shifts, during the months September to May 2006 to 2011. The probabilities of
      shark sightings were related to environmental variables using Binomial
      Generalized Additive Mixed Models (GAMMs). Sea surface temperature was
      significant, with the probability of shark sightings increasing rapidly as SST
      exceeded 14  degrees C and approached a maximum at 18  degrees C, whereafter it
      remains high. An 8 times (Muizenberg) and 5 times (Fish Hoek) greater likelihood
      of sighting a shark was predicted at 18  degrees C than at 14  degrees C. Lunar
      phase was also significant with a prediction of 1.5 times (Muizenberg) and 4
      times (Fish Hoek) greater likelihood of a shark sighting at new moon than at full
      moon. At Fish Hoek, the probability of sighting a shark was 1.6 times higher
      during the afternoon shift compared to the morning shift, but no diel effect was
      found at Muizenberg. A significant increase in the number of shark sightings was
      identified over the last three years, highlighting the need for ongoing research
      into shark attack mitigation. These patterns will be incorporated into shark
      awareness and bather safety campaigns in Cape Town.

PMID- 23874669
TI  - Linking plant nutritional status to plant-microbe interactions.
AB  - Plants have developed a wide-range of adaptations to overcome nutrient
      limitation, including changes to the quantity and composition of carbon
      containing compounds released by roots. Root-associated bacteria are largely
      influenced by these compounds which can be perceived as signals or substrates.
      Here, we evaluate the effect of root exudates collected from maize plants grown
      under nitrogen (N), phosphate (P), iron (Fe) and potassium (K) deficiencies on
      the transcriptome of the plant growth promoting rhizobacterium (PGPR) Bacillus
      amyloliquefaciens FZB42. The largest shifts in gene expression patterns were
      observed in cells exposed to exudates from N-, followed by P-deficient plants.
      Exudates from N-deprived maize triggered a general stress response in FZB42 in
      the exponential growth phase, which was evidenced by the suppression of numerous
      genes involved in protein synthesis. Exudates from P-deficient plants induced
      bacterial genes involved in chemotaxis and motility whilst exudates released by
      Fe and K deficient plants did not cause dramatic changes in the bacterial
      transcriptome during exponential growth phase. Global transcriptional changes in
      bacteria elicited by nutrient deficient maize exudates were significantly
      correlated with concentrations of the amino acids aspartate, valine and glutamate
      in root exudates suggesting that transcriptional profiling of FZB42 associated
      with metabolomics of N, P, Fe and K-deficient maize root exudates is a powerful
      approach to better understand plant-microbe interactions under conditions of
      nutritional stress. 

PMID- 23874670
TI  - Risk factors for small airway obstruction among Chinese island residents: a case
      control study.
AB  - BACKGROUND: We investigated the prevalence of and risk factors for small airway
      obstruction (SAO) among Chinese island residents to establish means to prevent
      and treat SAO. METHODS: From October 17, 2011 to November 1, 2011, a total of
      2,873 residents aged >20 years who lived on the Huangqi Peninsula of Fujian were
      recruited by random cluster sampling. They were asked to complete a Burden of
      Obstructive Lung Disease (BOLD) questionnaire and underwent physical examinations
      and lung function evaluations. SAO was defined as a forced expiratory flow at 50%
      of vital capacity, Vmax50%, of less than 70% of predicted. Risk factors for SAO
      were assessed from among demographic and anthropometric variables, blood
      chemistry results, and questionnaire response items. RESULTS: A total of 216
      (7.52%) Chinese island residents were identified as having SAO (95 males; 121
      females). Their survey and test results were compared with 432 age and sex
      matched healthy controls (192 males; 240 females) for SAO risk factors. Among
      numerous factors investigated, only diabetes mellitus (p = 0.039), smoking index
      (SI, p<0.001 for SI>600), second hand smoke (p = 0.002), and lack of regular
      exercise (p<0.001) were significant risk factors for SAO. CONCLUSIONS: The risk
      factors for SAO among Chinese island residents appeared to be similar to those
      among people who live in high-density urban environments and impoverished rural
      areas. Public health policies and medical practices directed toward improving
      respiratory health for island residents should be comparable to those used for
      urban and rural dwellers.

PMID- 23874671
TI  - Molecular insight into the steric shielding effect of PEG on the conjugated
      staphylokinase: biochemical characterization and molecular dynamics simulation.
AB  - PEGylation is a successful approach to improve potency of a therapeutic protein.
      The improved therapeutic potency is mainly due to the steric shielding effect of
      PEG. However, the underlying mechanism of this effect on the protein is not well
      understood, especially on the protein interaction with its high molecular weight
      substrate or receptor. Here, experimental study and molecular dynamics simulation
      were used to provide molecular insight into the interaction between the PEGylated
      protein and its receptor. Staphylokinase (Sak), a therapeutic protein for
      coronary thrombolysis, was used as a model protein. Four PEGylated Saks were
      prepared by site-specific conjugation of 5 kDa/20 kDa PEG to N-terminus and C
      terminus of Sak, respectively. Experimental study suggests that the native
      conformation of Sak is essentially not altered by PEGylation. In contrast, the
      bioactivity, the hydrodynamic volume and the molecular symmetric shape of the
      PEGylated Sak are altered and dependent on the PEG chain length and the
      PEGylation site. Molecular modeling of the PEGylated Saks suggests that the PEG
      chain remains highly flexible and can form a distinctive hydrated layer, thereby
      resulting in the steric shielding effect of PEG. Docking analyses indicate that
      the binding affinity of Sak to its receptor is dependent on the PEG chain length
      and the PEGylation site. Computational simulation results explain experimental
      data well. Our present study clarifies molecular details of PEG chain on protein
      surface and may be essential to the rational design, fabrication and clinical
      application of PEGylated proteins. 

PMID- 23874672
TI  - Iterative fragmentation of cognitive maps in a visual imagery task.
AB  - It remains unclear whether spontaneous eye movements during visual imagery
      reflect the mental generation of a visual image (i.e. the arrangement of the
      component parts of a mental representation). To address this specificity, we
      recorded eye movements in an imagery task and in a phonological fluency (non
      imagery) task, both consisting in naming French towns from long-term memory. Only
      in the condition of visual imagery the spontaneous eye positions reflected the
      geographic position of the towns evoked by the subjects. This demonstrates that
      eye positions closely reflect the mapping of mental images. Advanced analysis of
      gaze positions using the bi-dimensional regression model confirmed the spatial
      correlation of gaze and towns' locations in every single individual in the visual
      imagery task and in none of the individuals when no imagery accompanied memory
      retrieval. In addition, the evolution of the bi-dimensional regression's
      coefficient of determination revealed, in each individual, a process of
      generating several iterative series of a limited number of towns mapped with the
      same spatial distortion, despite different individual order of towns' evocation
      and different individual mappings. Such consistency across subjects revealed by
      gaze (the mind's eye) gives empirical support to theories postulating that visual
      imagery, like visual sampling, is an iterative fragmented processing. 

PMID- 23874673
TI  - Intralesional injection of rose bengal induces a systemic tumor-specific immune
      response in murine models of melanoma and breast cancer.
AB  - Intralesional (IL) injection of PV-10 has shown to induce regression of both
      injected and non-injected lesions in patients with melanoma. To determine an
      underlying immune mechanism, the murine B16 melanoma model and the MT-901 breast
      cancer model were utilized. In BALB/c mice bearing MT-901 breast cancer,
      injection of PV-10 led to regression of injected and untreated contralateral
      subcutaneous lesions. In a murine model of melanoma, B16 cells were injected into
      C57BL/6 mice to establish one subcutaneous tumor and multiple lung lesions.
      Treatment of the subcutaneous lesion with a single injection of IL PV-10 led to
      regression of the injected lesion as well as the distant B16 melanoma lung
      metastases. Anti-tumor immune responses were measured in splenocytes collected
      from mice treated with IL PBS or PV-10. Splenocytes isolated from tumor bearing
      mice treated with IL PV-10 demonstrated enhanced tumor-specific IFN-gamma
      production compared to splenocytes from PBS-treated mice in both models. In
      addition, a significant increase in lysis of B16 cells by T cells isolated after
      PV-10 treatment was observed. Transfer of T cells isolated from tumor-bearing
      mice treated with IL PV-10 led to tumor regression in mice bearing B16 melanoma.
      These studies establish that IL PV-10 therapy induces tumor-specific T cell
      mediated immunity in multiple histologic subtypes and support the concept of
      combining IL PV10 with immunotherapy for advanced malignancies. 

PMID- 23874674
TI  - Mapping the tail fiber as the receptor binding protein responsible for
      differential host specificity of Pseudomonas aeruginosa bacteriophages PaP1 and
      JG004.
AB  - The first step in bacteriophage infection is recognition and binding to the host
      receptor, which is mediated by the phage receptor binding protein (RBP).
      Different RBPs can lead to differential host specificity. In many bacteriophages,
      such as Escherichia coli and Lactococcal phages, RBPs have been identified as the
      tail fiber or protruding baseplate proteins. However, the tail fiber-dependent
      host specificity in Pseudomonas aeruginosa phages has not been well studied. This
      study aimed to identify and investigate the binding specificity of the RBP of P.
      aeruginosa phages PaP1 and JG004. These two phages share high DNA sequence
      homology but exhibit different host specificities. A spontaneous mutant phage was
      isolated and exhibited broader host range compared with the parental phage JG004.
      Sequencing of its putative tail fiber and baseplate region indicated a single
      point mutation in ORF84 (a putative tail fiber gene), which resulted in the
      replacement of a positively charged lysine (K) by an uncharged asparagine (N). We
      further demonstrated that the replacement of the tail fiber gene (ORF69) of PaP1
      with the corresponding gene from phage JG004 resulted in a recombinant phage that
      displayed altered host specificity. Our study revealed the tail fiber-dependent
      host specificity in P. aeruginosa phages and provided an effective tool for its
      alteration. These contributions may have potential value in phage therapy. 

PMID- 23874675
TI  - Effects of NMR spectral resolution on protein structure calculation.
AB  - Adequate digital resolution and signal sensitivity are two critical factors for
      protein structure determinations by solution NMR spectroscopy. The prime
      objective for obtaining high digital resolution is to resolve peak overlap,
      especially in NOESY spectra with thousands of signals where the signal analysis
      needs to be performed on a large scale. Achieving maximum digital resolution is
      usually limited by the practically available measurement time. We developed a
      method utilizing non-uniform sampling for balancing digital resolution and signal
      sensitivity, and performed a large-scale analysis of the effect of the digital
      resolution on the accuracy of the resulting protein structures. Structure
      calculations were performed as a function of digital resolution for about 400
      proteins with molecular sizes ranging between 5 and 33 kDa. The structural
      accuracy was assessed by atomic coordinate RMSD values from the reference
      structures of the proteins. In addition, we monitored also the number of assigned
      NOESY cross peaks, the average signal sensitivity, and the chemical shift
      spectral overlap. We show that high resolution is equally important for proteins
      of every molecular size. The chemical shift spectral overlap depends strongly on
      the corresponding spectral digital resolution. Thus, knowing the extent of
      overlap can be a predictor of the resulting structural accuracy. Our results show
      that for every molecular size a minimal digital resolution, corresponding to the
      natural linewidth, needs to be achieved for obtaining the highest accuracy
      possible for the given protein size using state-of-the-art automated NOESY
      assignment and structure calculation methods. 

PMID- 23874676
TI  - Improvement of the management of infants, children and adults with a molecular
      diagnosis of Enterovirus meningitis during two observational study periods.
AB  - Enteroviruses (EVs) are a major cause of aseptic meningitis, and RNA detection
      using molecular assay is the gold standard diagnostic test. The aim of this study
      was to assess the impact of an EV positive diagnosis on the clinical management
      of patients admitted for meningitis over the course of two observational study
      periods (2005 and 2008-09) in the same clinical departments. We further
      investigated in multivariate analysis various factors possibly associated with
      hospital length of stay (LOS) in all age groups (infants, children, and adults).
      The results showed an overall improvement in the management of patients (n = 142)
      between the study periods, resulting in a significantly shorter hospital LOS for
      adults and children, and a shorter duration of antibiotic use for adults and
      infants. In multivariate analysis, we observed that the time from molecular test
      results to discharge of patients and the median duration of antibiotic treatment
      were associated with an increase in LOS in all age groups. In addition, among
      adults, the turnaround time of the molecular assay was significantly correlated
      with LOS. The use of CT scan in children and hospital admission outside the peak
      of EV prevalence in infants tended to increase LOS. In conclusion, the shorter
      length of stay of patients with meningitis in this study was due to various
      factors including the rapidity of the EV molecular test (particularly in adults),
      greater physician responsiveness after a positive result (in adults and
      children), and greater experience on the part of physicians in handling EV
      meningitis, as evidenced by the shorter duration of antibiotic use in adults and
      infants. 

PMID- 23874677
TI  - An ochered fossil marine shell from the mousterian of fumane cave, Italy.
AB  - A scanty but varied ensemble of finds challenges the idea that Neandertal
      material culture was essentially static and did not include symbolic items. In
      this study we report on a fragmentary Miocene-Pliocene fossil marine shell,
      Aspamarginata, discovered in a Discoid Mousterian layer of the Fumane Cave,
      northern Italy, dated to at least 47.6-45.0 Cal ky BP. The shell was collected by
      Neandertals at a fossil exposure probably located more than 100 kms from the
      site. Microscopic analysis of the shell surface identifies clusters of striations
      on the inner lip. A dark red substance, trapped inside micropits produced by
      bioeroders, is interpreted as pigment that was homogeneously smeared on the outer
      shell surface. Dispersive X-ray and Raman analysis identify the pigment as pure
      hematite. Of the four hypotheses we considered to explain the presence of this
      object at the site, two (tool, pigment container) are discarded because in
      contradiction with observations. Although the other two ("manuport", personal
      ornament) are both possible, we favor the hypothesis that the object was modified
      and suspended by a 'thread' for visual display as a pendant. Together with
      contextual and chronometric data, our results support the hypothesis that
      deliberate transport and coloring of an exotic object, and perhaps its use as
      pendant, was a component of Neandertal symbolic culture, well before the earliest
      appearance of the anatomically modern humans in Europe. 

PMID- 23874678
TI  - Diminishing returns from increased percent Bt cotton: the case of pink bollworm.
AB  - Regional suppression of pests by transgenic crops producing insecticidal proteins
      from Bacillus thuringiensis (Bt) has been reported in several cropping systems,
      but little is known about the functional relationship between the ultimate pest
      population density and the pervasiveness of Bt crops. Here we address this issue
      by analyzing 16 years of field data on pink bollworm (Pectinophora gossypiella)
      population density and percentage of Bt cotton in the Yangtze River Valley of
      China. In this region, the percentage of cotton hectares planted with Bt cotton
      increased from 9% in 2000 to 94% in 2009 and 2010. We find that as the percent Bt
      cotton increased over the years, the cross-year growth rate of pink bollworm from
      the last generation of one year to the first generation of the next year
      decreased. However, as the percent Bt cotton increased, the within-year growth
      rate of pink bollworm from the first to last generation of the same year
      increased, with a slope approximately opposite to that of the cross-year rates.
      As a result, we did not find a statistically significant decline in the annual
      growth rate of pink bollworm as the percent Bt cotton increased over time.
      Consistent with the data, our modeling analyses predict that the regional average
      density of pink bollworm declines as the percent Bt cotton increases, but the
      higher the percent Bt cotton, the slower the decline in pest density.
      Specifically, we find that 95% Bt cotton is predicted to cause only 3% more
      reduction in larval density than 80% Bt cotton. The results here suggest that
      density dependence can act against the decline in pest density and diminish the
      net effects of Bt cotton on suppression of pink bollworm in the study region. The
      findings call for more studies of the interactions between pest density
      dependence and Bt crops. 

PMID- 23874679
TI  - Assessment of motor function, sensory motor gating and recognition memory in a
      novel BACHD transgenic rat model for huntington disease.
AB  - RATIONALE: Huntington disease (HD) is frequently first diagnosed by the
      appearance of motor symptoms; the diagnosis is subsequently confirmed by the
      presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat
      model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats
      has been established recently. Behavioral phenotyping of BACHD rats will help to
      determine the validity of this model and its potential use in preclinical drug
      discovery studies. OBJECTIVES: The present study seeks to characterize the
      progressive emergence of motor, sensorimotor and cognitive deficits in BACHD
      rats. MATERIALS AND METHODS: Wild type and transgenic rats were tested from 1
      till 12 months of age. Motor tests were selected to measure spontaneous locomotor
      activity (open field) and gait coordination. Sensorimotor gating was assessed in
      acoustic startle response paradigms and recognition memory was evaluated in an
      object recognition test. RESULTS: Transgenic rats showed hyperactivity at 1 month
      and hypoactivity starting at 4 months of age. Motor coordination imbalance in a
      Rotarod test was present at 2 months and gait abnormalities were seen in a
      Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas
      object recognition was unimpaired in BACHD rats up to 12 months of age.
      CONCLUSION: The current BACHD rat model recapitulates certain symptoms from HD
      patients, especially the marked motor deficits. A subtle neuropsychological
      phenotype was found and further studies are needed to fully address the
      sensorimotor phenotype and the potential use of BACHD rats for drug discovery
      purposes.

PMID- 23874680
TI  - Combination therapy of VEGF-trap and gemcitabine results in improved anti-tumor
      efficacy in a mouse lung cancer model.
AB  - BACKGROUND: Angiogenesis is essential for the growth and metastasis of cancer.
      Although anti-angiogenic agents, particularly vascular endothelial growth factor
      (VEGF) inhibitors, have exhibited single-agent activity, there is considerable
      interest in combining these novel drugs with conventional chemotherapy reagents
      to achieve an optimal clinical efficacy. The objective of this study was to
      evaluate the benefits of the combination therapy of vascular endothelial growth
      factor trap (VEGF-Trap) with gemcitabine in a lung tumor model. METHODS: A
      luciferase-expressing Lewis lung carcinoma (LLC) model was established in
      C57BL/6J mice and tumor-bearing mice were randomized into control, VEGF-Trap,
      gemcitabine and VEGF-Trap/gemcitabine combination groups. Tumor growth and animal
      survival were monitored. Tumor microvessel density and cell proliferation were
      evaluated by CD31 and Ki-67 immunohistochemical analysis. TUNEL assay was
      performed to detect apoptotic cells. The protein levels of Cyclin D1, Pro-Caspase
      3, Bcl-2, MMP2 and MMP9 in tumor extracts were examined by western blot. RESULTS:
      VEGF-Trap in combination with gemcitabine showed significantly enhanced
      inhibition of tumor growth and prolonged mouse survival compared to the VEGF-Trap
      or gemcitabine monotherapy. The VEGF-Trap/gemcitabine combination therapy not
      only potently inhibited tumor angiogenesis and cell proliferation, but also
      increased cellular apoptosis within tumor tissues. In addition, the combination
      treatment markedly down-regulated the expression of proliferation, anti-apoptosis
      and invasion related proteins. CONCLUSION: Combination therapy using VEGF-Trap
      and gemcitabine resulted in improved anti-tumor efficacy in a lung cancer model
      and VEGF-Trap/gemcitabine combination might represent a promising strategy in the
      treatment of human lung cancer.

PMID- 23874681
TI  - Welcome to wonderland: the influence of the size and shape of a virtual hand on
      the perceived size and shape of virtual objects.
AB  - The notion of body-based scaling suggests that our body and its action
      capabilities are used to scale the spatial layout of the environment. Here we
      present four studies supporting this perspective by showing that the hand acts as
      a metric which individuals use to scale the apparent sizes of objects in the
      environment. However to test this, one must be able to manipulate the size and/or
      dimensions of the perceiver's hand which is difficult in the real world due to
      impliability of hand dimensions. To overcome this limitation, we used virtual
      reality to manipulate dimensions of participants' fully-tracked, virtual hands to
      investigate its influence on the perceived size and shape of virtual objects. In
      a series of experiments, using several measures, we show that individuals'
      estimations of the sizes of virtual objects differ depending on the size of their
      virtual hand in the direction consistent with the body-based scaling hypothesis.
      Additionally, we found that these effects were specific to participants' virtual
      hands rather than another avatar's hands or a salient familiar-sized object.
      While these studies provide support for a body-based approach to the scaling of
      the spatial layout, they also demonstrate the influence of virtual bodies on
      perception of virtual environments. 

PMID- 23874682
TI  - Microbial reprogramming inhibits Western diet-associated obesity.
AB  - A recent epidemiological study showed that eating 'fast food' items such as
      potato chips increased likelihood of obesity, whereas eating yogurt prevented age
      associated weight gain in humans. It was demonstrated previously in animal models
      of obesity that the immune system plays a critical role in this process. Here we
      examined human subjects and mouse models consuming Westernized 'fast food' diet,
      and found CD4(+) T helper (Th)17-biased immunity and changes in microbial
      communities and abdominal fat with obesity after eating the Western chow. In
      striking contrast, eating probiotic yogurt together with Western chow inhibited
      age-associated weight gain. We went on to test whether a bacteria found in yogurt
      may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC
      6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy
      alone was sufficient to change the pro-inflammatory immune cell profile and
      prevent abdominal fat pathology and age-associated weight gain in mice regardless
      of their baseline diet. These beneficial microbe effects were transferable into
      naive recipient animals by purified CD4(+) T cells alone. Specifically, bacterial
      effects depended upon active immune tolerance by induction of Foxp3(+) regulatory
      T cells (Treg) and interleukin (Il)-10, without significantly changing the gut
      microbial ecology or reducing ad libitum caloric intake. Our finding that
      microbial targeting restored CD4(+) T cell balance and yielded significantly
      leaner animals regardless of their dietary 'fast food' indiscretions suggests
      population-based approaches for weight management and enhancing public health in
      industrialized societies. 

PMID- 23874683
TI  - Overexpression of GATA1 confers resistance to chemotherapy in acute
      megakaryocytic Leukemia.
AB  - It has been previously shown that acute myeloid leukemia (AML) patients with
      higher levels of GATA1 expression have poorer outcomes. Furthermore, pediatric
      Down syndrome (DS) patients with acute megakaryocytic leukemia (AMKL), whose
      blast cells almost universally harbor somatic mutations in exon 2 of the
      transcription factor gene GATA1, demonstrate increased overall survival relative
      to non-DS pediatric patients, suggesting a potential role for GATA1 in
      chemotherapy response. In this study, we confirmed that amongst non-DS patients,
      GATA1 transcripts were significantly higher in AMKL blasts compared to blasts
      from other AML subgroups. Further, GATA1 transcript levels significantly
      correlated with transcript levels for the anti-apoptotic protein Bcl-xL in our
      patient cohort. ShRNA knockdown of GATA1 in the megakaryocytic cell line Meg-01
      resulted in significantly increased cytarabine (ara-C) and daunorubicin anti
      proliferative sensitivities and decreased Bcl-xL transcript and protein levels.
      Chromatin immunoprecipitation (ChIP) and reporter gene assays demonstrated that
      the Bcl-x gene (which transcribes the Bcl-xL transcripts) is a bona fide GATA1
      target gene in AMKL cells. Treatment of the Meg-01 cells with the histone
      deacetylase inhibitor valproic acid resulted in down-regulation of both GATA1 and
      Bcl-xL and significantly enhanced ara-C sensitivity. Furthermore, additional
      GATA1 target genes were identified by oligonucleotide microarray and ChIP-on-Chip
      analyses. Our findings demonstrate a role for GATA1 in chemotherapy resistance in
      non-DS AMKL cells, and identified additional GATA1 target genes for future
      studies. 

PMID- 23874684
TI  - Identification of HSP90 as potential biomarker of biliary atresia using two
      dimensional electrophoresis and mass spectrometry.
AB  - Biliary atresia (BA) is a devastating cholestatic liver disease targeting
      infants. Current diagnosis depends on surgical exploration of the biliary tree.
      The aim of the present study was to identify potential biomarkers for the
      diagnosis of biliary atresia (BA). Two-dimensional electrophoresis was utilized
      for the identification of proteins that were differentially expressed in liver
      biopsies of 20 BA patients and 12 infants with non-BA neonatal cholestasis (NC)
      as controls. Using mass spectrometry, we identified 15 proteins with expressions
      significantly altered. Out of the 15 proteins identified, heat shock protein
      (HSP) 90 was the most significantly altered and was down-regulated in BA samples
      compared to NC samples using immunoblotting analysis. Our findings suggest that
      HSP90 might be a potential biomarker for the diagnosis of BA and may be used for
      monitoring further development and therapy for BA. This study demonstrated that a
      comprehensive strategy of proteomic identification combined with further
      validation should be adopted in biomarker discovery. 

PMID- 23874685
TI  - Local exome sequences facilitate imputation of less common variants and increase
      power of genome wide association studies.
AB  - The analysis of less common variants in genome-wide association studies promises
      to elucidate complex trait genetics but is hampered by low power to reliably
      detect association. We show that addition of population-specific exome sequence
      data to global reference data allows more accurate imputation, particularly of
      less common SNPs (minor allele frequency 1-10%) in two very different European
      populations. The imputation improvement corresponds to an increase in effective
      sample size of 28-38%, for SNPs with a minor allele frequency in the range 1-3%. 

PMID- 23874686
TI  - Downregulation of microRNA-130a contributes to endothelial progenitor cell
      dysfunction in diabetic patients via its target Runx3.
AB  - Dysfunction of endothelial progenitor cells (EPCs) contributes to diabetic
      vascular disease. MicroRNAs (miRs) have emerged as key regulators of diverse
      cellular processes including angiogenesis. We recently reported that miR-126, miR
      130a, miR-21, miR-27a, and miR-27b were downregulated in EPCs from type II
      diabetes mellitus (DM) patients, and downregulation of miR-126 impairs EPC
      function. The present study further explored whether dysregulated miR-130a were
      also related to EPC dysfunction. EPCs were cultured from peripheral blood
      mononuclear cells of diabetic patients and healthy controls. Assays on EPC
      function (proliferation, migration, differentiation, apoptosis, and colony and
      tubule formation) were performed. Bioinformatics analyses were used to identify
      the potential targets of miR-130a in EPCs. Gene expression of miR-103a and Runx3
      was measured by real-time PCR, and protein expression of Runx3, extracellular
      signal-regulated kinase (ERK), vascular endothelial growth factor (VEGF) and Akt
      was measured by Western blotting. Runx3 promoter activity was measured by
      luciferase reporter assay. A miR-130a inhibitor or mimic and lentiviral vectors
      expressing miR-130a, or Runx3, or a short hairpin RNA targeting Runx3 were
      transfected into EPCs to manipulate miR-130a and Runx3 levels. MiR-130a was
      decreased in EPCs from DM patients. Anti-miR-130a inhibited whereas miR-130a
      overexpression promoted EPC function. miR-130a negatively regulated Runx3 (mRNA,
      protein and promoter activity) in EPCs. Knockdown of Runx3 expression enhanced
      EPC function. MiR-130a also upregulated protein expression of ERK/VEGF and Akt in
      EPCs. In conclusion, miR-130a plays an important role in maintaining normal EPC
      function, and decreased miR-130a in EPCs from DM contributes to impaired EPC
      function, likely via its target Runx3 and through ERK/VEGF and Akt pathways. 

PMID- 23874687
TI  - Pioglitazone improves reversal learning and exerts mixed cerebrovascular effects
      in a mouse model of Alzheimer's disease with combined amyloid-beta and
      cerebrovascular pathology.
AB  - Animal models of Alzheimer's disease (AD) are invaluable in dissecting the
      pathogenic mechanisms and assessing the efficacy of potential new therapies.
      Here, we used the peroxisome proliferator-activated receptor gamma agonist
      pioglitazone in an attempt to rescue the pathogenic phenotype in adult (12
      months) and aged (>18 months) bitransgenic A/T mice that overexpress a mutated
      human amyloid precursor protein (APPSwe,Ind) and a constitutively active form of
      transforming growth factor-beta1 (TGF-beta1). A/T mice recapitulate the AD
      related cognitive deficits, amyloid beta (Abeta) and cerebrovascular pathologies,
      as well as the altered metabolic and vascular coupling responses to increased
      neuronal activity. Pioglitazone normalized neurometabolic and neurovascular
      coupling responses to sensory stimulation, and reduced cortical astroglial and
      hippocampal microglial activation in both age groups. Spatial learning and memory
      deficits in the Morris water maze were not rescued by pioglitazone, but reversal
      learning was improved in the adult cohort notwithstanding a progressing Abeta
      pathology. While pioglitazone preserved the constitutive nitric oxide synthesis
      in the vessel wall, it unexpectedly failed to restore cerebrovascular reactivity
      in A/T mice and even exacerbated the dilatory deficits. These data demonstrate
      pioglitazone's efficacy on selective AD hallmarks in a complex AD mouse model of
      comorbid amyloidosis and cerebrovascular pathology. They further suggest a
      potential benefit of pioglitazone in managing neuroinflammation, cerebral
      perfusion and glucose metabolism in AD patients devoid of cerebrovascular
      pathology. 

PMID- 23874688
TI  - Inhibition of GSK 3beta activity is associated with excessive EZH2 expression and
      enhanced tumour invasion in nasopharyngeal carcinoma.
AB  - BACKGROUND: Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to
      tumour development and/or progression. However, the signalling pathway underlying
      the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since
      EZH2 contains the putative Glycogen synthase kinase 3 beta (GSK3beta)
      phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of
      GSK-3beta, it is possible that inactivation of GSK3beta may lead to excessive
      EZH2 expression in NPC. METHOD: We first examined the expression of EZH2 and
      phosphorylated GSK3beta (p-GSK3beta) by immunohistochemical staining in NPC
      samples. Then, we evaluated the interaction of GSK3beta and EZH2 using
      immunoprecipitation and immune blot. Moreover, we determined the effect of
      inhibition of GSK3beta activity on EZH2 expression and tumor invasiveness in NPC
      cell lines in vitro. Finally, we evaluated the invasive properties of NPC cells
      after knocking down EZH2 expression with EZH2 siRNA. RESULTS: We found that
      expression of EZH2 correlated with phosphorylated GSK3beta (p-GSK3beta) at Ser 9
      (an inactivated form of GSK3beta) in human nasopharyngeal carcinoma (NPC)
      samples. We also provided evidence that GSK3beta is able to interact with EZH2
      using immunoprecipitation and immune blot. Furthermore, we found that inhibition
      of GSK3beta activity can lead to upregulation of EZH2 in NPC cell lines in vitro,
      with enhanced local invasiveness. By knocking down EZH2 expression with EZH2
      siRNA, we found that these invasive properties were EZH2 dependent. CONCLUSION:
      Our findings indicate that GSK3beta inactivation may account for EZH2
      overexpression and subsequent tumour progression, and this mechanism might be a
      potential target for NPC therapy.

PMID- 23874690
TI  - Agreement among healthcare professionals in ten European countries in diagnosing
      case-vignettes of surgical-site infections.
AB  - OBJECTIVE: Although surgical-site infection (SSI) rates are advocated as a major
      evaluation criterion, the reproducibility of SSI diagnosis is unknown. We
      assessed agreement in diagnosing SSI among specialists involved in SSI
      surveillance in Europe. METHODS: Twelve case-vignettes based on suspected SSI
      were submitted to 100 infection-control physicians (ICPs) and 86 surgeons in 10
      European countries. Each participant scored eight randomly-assigned case
      vignettes on a secure online relational database. The intra-class correlation
      coefficient (ICC) was used to assess agreement for SSI diagnosis on a 7-point
      Likert scale and the kappa coefficient to assess agreement for SSI depth on a
      three-point scale. RESULTS: Intra-specialty agreement for SSI diagnosis ranged
      across countries and specialties from 0.00 (95%CI, 0.00-0.35) to 0.65 (0.45
      0.82). Inter-specialty agreement varied from 0.04 (0.00-0.62) in to 0.55 (0.37
      0.74) in Germany. For all countries pooled, intra-specialty agreement was poor
      for surgeons (0.24, 0.14-0.42) and good for ICPs (0.41, 0.28-0.61). Reading SSI
      definitions improved agreement among ICPs (0.57) but not surgeons (0.09). Intra
      specialty agreement for SSI depth ranged across countries and specialties from
      0.05 (0.00-0.10) to 0.50 (0.45-0.55) and was not improved by reading SSI
      definition. CONCLUSION: Among ICPs and surgeons evaluating case-vignettes of
      suspected SSI, considerable disagreement occurred regarding the diagnosis, with
      variations across specialties and countries.

PMID- 23874689
TI  - Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced
      mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent
      glucose transporter SGLT1.
AB  - Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known
      as anthocyanins that occur naturally in pigmented plants and are known to
      ameliorate oxidative stress. Previous studies have showed that Dp decreased
      oxidative stress in vascular endothelial cells, however, the underlying
      mechanisms remain largely unknown. In the present study, we showed that
      pretreatment with Dp significantly suppressed oxidized low-density lipoprotein
      (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human
      umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL
      induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and
      superoxide anion generation, thereby repressing mitochondrial membrane potential
      and closing mitochondrial permeability transition pore. Furthermore, in vitro and
      in vivo data showed that Dp was transported into endothelial cells in a
      temperature, concentration, and time-dependent manner via the sodium-dependent
      glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its
      inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1
      significantly inhibited Dp function of ameliorating mitochondrial dysfunction
      induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c,
      Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp
      protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to
      elucidate the molecular mechanisms underlying the vascular protection afforded by
      Dp, and anthocyanins in general, in the context of prevention of endothelial
      dysfunction and atherosclerosis. 

PMID- 23874691
TI  - Distributions of cranial pathologies provide evidence for head-butting in dome
      headed dinosaurs (Pachycephalosauridae).
AB  - Pachycephalosaurids are small, herbivorous dinosaurs with domed skulls formed by
      massive thickening of the cranial roof. The function of the dome has been a focus
      of debate: the dome has variously been interpreted as the product of sexual
      selection, as an adaptation for species recognition, or as a weapon employed in
      intraspecific combat, where it was used in butting matches as in extant
      ungulates. This last hypothesis is supported by the recent identification of
      cranial pathologies in pachycephalosaurids, which appear to represent infections
      resulting from trauma. However, the frequency and distribution of pathologies
      have not been studied in a systematic fashion. Here, we show that
      pachycephalosaurids are characterized by a remarkably high incidence of cranial
      injury, where 22% of specimens have lesions on the dome. Frequency of injury
      shows no significant difference between different genera, but flat-headed morphs
      (here interpreted as juveniles or females) lack lesions. Mapping of injuries onto
      a digitial pachycephalosaurid skull shows that although lesions are distributed
      across the dome, they cluster near the apex, which is consistent with the
      hypothesis that the dome functioned for intraspecific butting matches. 

PMID- 23874692
TI  - Adaptive modulation of adult brain gray and white matter to high altitude:
      structural MRI studies.
AB  - The aim of this study was to investigate brain structural alterations in adult
      immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of
      gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract
      Based Spatial Statistics analysis of white matter fractional anisotropy (FA)
      based on MRI images were conducted on 16 adults (20-22 years) who immigrated to
      the Qinghai-Tibet Plateau (2300-4400 m) for 2 years. They had no chronic mountain
      sickness. Control group consisted of 16 matched sea level subjects. A battery of
      neuropsychological tests was also conducted. HA immigrants showed significantly
      decreased GM volumes in the right postcentral gyrus and right superior frontal
      gyrus, and increased GM volumes in the right middle frontal gyrus, right
      parahippocampal gyrus, right inferior and middle temporal gyri, bilateral
      inferior ventral pons, and right cerebellum crus1. While there was some
      divergence in the left hemisphere, surface-based patterns of GM changes in the
      right hemisphere resembled those seen for VBM analysis. FA changes were observed
      in multiple WM tracts. HA immigrants showed significant impairment in pulmonary
      function, increase in reaction time, and deficit in mental rotation.
      Parahippocampal and middle frontal GM volumes correlated with vital capacity.
      Superior frontal GM volume correlated with mental rotation and postcentral GM
      correlated with reaction time. Paracentral lobule and frontal FA correlated with
      mental rotation reaction time. There might be structural modifications occurred
      in the adult immigrants during adaptation to HA. The changes in GM may be related
      to impaired respiratory function and psychological deficits. 

PMID- 23874693
TI  - Differentiating laryngeal carcinomas from precursor lesions by diffusion-weighted
      magnetic resonance imaging at 3.0 T: a preliminary study.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) has been
      introduced in head and neck cancers. Due to limitations in the performance of
      laryngeal DWI, including the complex anatomical structure of the larynx leading
      to susceptibility effects, the value of DWI in differentiating benign from
      malignant laryngeal lesions has largely been ignored. We assessed whether a
      threshold for the apparent diffusion coefficient (ADC) was useful in
      differentiating preoperative laryngeal carcinomas from precursor lesions by turbo
      spin-echo (TSE) DWI and 3.0-T magnetic resonance. METHODS: We evaluated DWI and
      the ADC value in 33 pathologically proven laryngeal carcinomas and 17
      precancerous lesions. RESULTS: The sensitivity, specificity, and accuracy were
      81.8%, 64.7%, 76.0% by laryngostroboscopy, respectively. The sensitivity,
      specificity, and accuracy of conventional magnetic resonance imaging were 90.9%,
      76.5%, 86.0%, respectively. Qualitative DWI analysis produced sensitivity,
      specificity, and accuracy values of 100.0, 88.2, and 96.0%, respectively. The ADC
      values were lower for patients with laryngeal carcinoma (mean 1.195+/-0.32*10(-3)
      mm(2)/s) versus those with laryngeal precancerous lesions (mean 1.780+/-0.32*10(
      3) mm(2)/s; P<0.001). ROC analysis showed that the area under the curve was 0.956
      and the optimum threshold for the ADC was 1.455*10(-3) mm(2)/s, resulting in a
      sensitivity of 94.1%, a specificity of 90.9%, and an accuracy of 92.9%.
      CONCLUSIONS: Despite some limitations, including the small number of laryngeal
      carcinomas included, DWI may detect changes in tumor size and shape before they
      are visible by laryngostroboscopy. The ADC values were lower for patients with
      laryngeal carcinoma than for those with laryngeal precancerous lesions. The
      proposed cutoff for the ADC may help distinguish laryngeal carcinomas from
      laryngeal precancerous lesions.

PMID- 23874694
TI  - Ouabain suppresses the migratory behavior of lung cancer cells.
AB  - The migratory capability of cancer cells is one of the most important hallmarks
      reflecting metastatic potential. Ouabain, an endogenous cardiac glycoside
      produced by the adrenal gland, has been previously reported to have anti-tumor
      activities; however, its role in the regulation of cancer cell migration remains
      unknown. The present study has revealed that treatment with ouabain at
      physiological concentrations is able to inhibit the migratory activities of human
      lung cancer H292 cells. The negative effects of ouabain were found to be mediated
      through the suppression of migration regulatory proteins, such as focal adhesion
      kinase (FAK), ATP-dependent tyrosine kinase (Akt), and cell division cycle 42
      (Cdc42). We found that the observed actions of ouabain were mediated via a
      reactive oxygen species (ROS)-dependent mechanism because the addition of ROS
      scavengers (N-acetylcysteine and glutathione) could reverse the effect of ouabain
      on cell migration. Furthermore, ouabain was shown to inhibit the spheroidal tumor
      growth and decrease the cancer cell adhesion to endothelial cells. However, the
      compound had no significant effect on anoikis of the cells. Together, these
      findings shed light on the understanding of cancer cell biology by exploring the
      novel function of this endogenous human substance. 

PMID- 23874695
TI  - Diversity in protein profiles of individual calcium oxalate kidney stones.
AB  - Calcium oxalate kidney stones contain low amounts of proteins, some of which have
      been implicated in progression or prevention of kidney stone formation. To gain
      insights into the pathophysiology of urolithiasis, we have characterized protein
      components of calcium oxalate kidney stones by proteomic approaches. Proteins
      extracted from kidney stones showed highly heterogeneous migration patterns in
      gel electrophoresis as reported. This was likely to be mainly due to proteolytic
      degradation and protein-protein crosslinking of Tamm-Horsfall protein and
      prothrombin. Protein profiles of calcium oxalate kidney stones were obtained by
      in-solution protease digestion followed by nanoLC-MALDI-tandem mass spectrometry,
      which resulted in identification of a total of 92 proteins in stones from 9
      urolithiasis patients. Further analysis showed that protein species and their
      relative amounts were highly variable among individual stones. Although proteins
      such as prothrombin, osteopontin, calgranulin A and calgranulin B were found in
      most stones tested, some samples had high contents of prothrombin and
      osteopontin, while others had high contents of calgranulins. In addition,
      calgranulin-rich stones had various neutrophil-enriched proteins such as
      myeloperoxidase and lactotransferrin. These proteomic profiles of individual
      kidney stones suggest that multiple systems composed of different groups of
      proteins including leucocyte-derived ones are differently involved in
      pathogenesis of individual kidney stones depending on situations. 

PMID- 23874696
TI  - Cortical shape and curvedness analysis of structural deficits in remitting and
      non-remitting depression.
AB  - In morphometric neuroimaging studies, the relationship between brain structural
      changes and the antidepressant treatment response in patients with major
      depressive disorder has been explored to search depression-trait biomarkers.
      Although patients were treated with serotonin-related drugs, whether the same
      treatment resulted in remission and non-remission in depressed patients is
      currently under investigation. We recruited 25 depressed patients and 25 healthy
      controls and acquired volumetric magnetic resonance imaging of each participant.
      We used the shape index and curvedness to classify cortical shapes and quantify
      shape complexities, respectively, in studying the pharmacological effect on brain
      morphology. The results showed that different regions of structural abnormalities
      emerged between remitting and non-remitting patients when contrasted with healthy
      controls. In addition to comparing structural metrics in each cortical
      parcellation, similar to the traditional voxel-based morphometric method, we
      highlighted the importance of structural integrity along the serotonin pathway in
      response to medication treatment. We discovered that disrupted serotonin-related
      cortical regions might cause non-remission to antidepressant treatment from a
      pharmacological perspective. The anomalous areas manifested in non-remitting
      patients were mainly in the frontolimbic areas, which can be used to
      differentiate remitting from non-remitting participants before medication
      treatment. Because non-remission is the failure to respond to treatment with
      serotonin-related drugs, our method may help clinicians choose appropriate
      medications for non-remitting patients. 

PMID- 23874697
TI  - Sox2 transcriptionally regulates PQBP1, an intellectual disability-microcephaly
      causative gene, in neural stem progenitor cells.
AB  - PQBP1 is a nuclear-cytoplasmic shuttling protein that is engaged in RNA
      metabolism and transcription. In mouse embryonic brain, our previous in situ
      hybridization study revealed that PQBP1 mRNA was dominantly expressed in the
      periventricular zone region where neural stem progenitor cells (NSPCs) are
      located. Because the expression patterns in NSPCs are related to the symptoms of
      intellectual disability and microcephaly in PQBP1 gene-mutated patients, we
      investigated the transcriptional regulation of PQBP1 by NSPC-specific
      transcription factors. We selected 132 genome sequences that matched the
      consensus sequence for the binding of Sox2 and POU transcription factors upstream
      and downstream of the mouse PQBP1 gene. We then screened the binding affinity of
      these sequences to Sox2-Pax6 or Sox2-Brn2 with gel mobility shift assays and
      found 18 genome sequences that interacted with the NSPC-specific transcription
      factors. Some of these sequences had cis-regulatory activities in Luciferase
      assays and in utero electroporation into NSPCs. Furthermore we found decreased
      levels of expression of PQBP1 protein in NSPCs of heterozygous Sox2-knockout mice
      in vivo by immunohistochemistry and western blot analysis. Collectively, these
      results indicated that Sox2 regulated the transcription of PQBP1 in NSPCs. 

PMID- 23874698
TI  - The bidirectional association between depressive symptoms and gait speed:
      evidence from the English Longitudinal Study of Ageing (ELSA).
AB  - BACKGROUND: Depressive symptoms and physical performance are inversely
      associated, but it is unclear whether their association is bidirectional. We
      examined whether the association between depressive symptoms and physical
      performance measured using gait speed is bidirectional. METHODS: We used a
      national sample of 4,581 community-dwelling people aged 60 years and older from
      the English Longitudinal Study of Ageing (from 2002-03 to 2008-09). We fitted
      Generalized Estimating Equation (GEE) regression models to analyse repeated
      measurements of gait speed (m/sec) and elevated depressive symptoms (defined as a
      score of >=4 on the eight-item Center for Epidemiological Studies-Depression
      scale). RESULTS: Slower gait speed was associated with elevated depressive
      symptoms both concurrently and two years later. After adjustment for previous
      depressive symptoms and sociodemographic, clinical, lifestyle, psychosocial, and
      cognitive factors the concurrent association was partially explained (Odds Ratio
      [OR] 0.42, 95% confidence interval [CI], 0.30 to 0.59, per 1m/sec increase in
      gait speed) and the two-year lagged association fully (OR 0.75, 95% CI, 0.56 to
      1.00). Elevated depressive symptoms were associated with slower gait speed. Full
      adjustment for covariates (including previous gait speed) partially explained
      both the concurrent (beta regression coefficient [beta] -0.038, 95% CI, -0.050 to
      -0.026, for participants with elevated depressive symptoms compared with those
      with no or one symptom) and the two-year lagged associations (beta -0.017, 95%
      CI, -0.030 to -0.005). Subthreshold depressive symptoms (defined as a score of
      two or three on the eight-item Center for Epidemiological Studies-Depression
      scale) were also associated with slower gait speed. Full adjustment for
      covariates partially explained both the concurrent (beta -0.029, 95% CI, -0.039
      to -0.019, for participants with subthreshold symptoms compared with those with
      no or one symptom) and the two-year lagged associations (beta -0.011, 95% CI, 
      0.021 to -0.001). CONCLUSIONS: The inverse association between gait speed and
      depressive symptoms appears to be bidirectional.

PMID- 23874699
TI  - Influenza risk management: lessons learned from an A(H1N1) pdm09 outbreak
      investigation in an operational military setting.
AB  - BACKGROUND: At the onset of an influenza pandemic, when the severity of a novel
      strain is still undetermined and there is a threat of introduction into a new
      environment, e.g., via the deployment of military troops, sensitive screening
      criteria and conservative isolation practices are generally recommended.
      OBJECTIVES: In response to elevated rates of influenza-like illness among U.S.
      military base camps in Kuwait, U.S. Naval Medical Research Unit No. 3 partnered
      with local U.S. Army medical units to conduct an A(H1N1) pdm09 outbreak
      investigation. PATIENTS/METHODS: Initial clinical data and nasal specimens were
      collected via the existent passive surveillance system and active surveillance
      was conducted using a modified version of the World Health Organization/U.S.
      Centers for Disease Control and Prevention influenza-like illness case definition
      [fever (T > 100.5F/38C) in addition to cough and/or sore throat in the previous
      72 hours] as the screening criteria. Samples were tested via real-time reverse
      transcription PCR and sequenced for comparison to global A(H1N1) pdm09 viruses
      from the same time period. RESULTS: The screening criteria used in Kuwait proved
      insensitive, capturing only 16% of A(H1N1) pdm09-positive individuals. While
      still not ideal, using cough as the sole screening criteria would have increased
      sensitivity to 73%. CONCLUSIONS: The results of and lessons learned from this
      outbreak investigation suggest that pandemic influenza risk management should be
      a dynamic process (as information becomes available regarding true attack rates
      and associated mortality, screening and isolation criteria should be re-evaluated
      and revised as appropriate), and that military operational environments present
      unique challenges to influenza surveillance.

PMID- 23874700
TI  - Drosophila adiponectin receptor in insulin producing cells regulates glucose and
      lipid metabolism by controlling insulin secretion.
AB  - Adipokines secreted from adipose tissue are key regulators of metabolism in
      animals. Adiponectin, one of the adipokines, modulates pancreatic beta cell
      function to maintain energy homeostasis. Recently, significant conservation
      between Drosophila melanogaster and mammalian metabolism has been discovered.
      Drosophila insulin like peptides (Dilps) regulate energy metabolism similarly to
      mammalian insulin. However, in Drosophila, the regulatory mechanism of insulin
      producing cells (IPCs) by adipokine signaling is largely unknown. Here, we
      describe the discovery of the Drosophila adiponectin receptor and its function in
      IPCs. Drosophila adiponectin receptor (dAdipoR) has high homology with the human
      adiponectin receptor 1. The dAdipoR antibody staining revealed that dAdipoR was
      expressed in IPCs of larval and adult brains. IPC- specific dAdipoR inhibition
      (Dilp2>dAdipoR-Ri) showed the increased sugar level in the hemolymph and the
      elevated triglyceride level in whole body. Dilps mRNA levels in the Dilp2>dAdipoR
      Ri flies were similar with those of controls. However, in the Dilp2>dAdipoR-Ri
      flies, Dilp2 protein was accumulated in IPCs, the level of circulating Dilp2 was
      decreased, and insulin signaling was reduced in the fat body. In ex vivo fly
      brain culture with the human adiponectin, Dilp2 was secreted from IPCs. These
      results indicate that adiponectin receptor in insulin producing cells regulates
      insulin secretion and controls glucose and lipid metabolism in Drosophila
      melanogaster. This study demonstrates a new adipokine signaling in Drosophila and
      provides insights for the mammalian adiponectin receptor function in pancreatic
      beta cells, which could be useful for therapeutic application. 

PMID- 23874701
TI  - Increased circulating endothelial apoptotic microparticle to endothelial
      progenitor cell ratio is associated with subsequent decline in glomerular
      filtration rate in hypertensive patients.
AB  - BACKGROUND: Recent research indicates hypertensive patients with microalbuminuria
      have decreased endothelial progenitor cells (EPCs) and increased levels of
      endothelial apoptotic microparticles (EMP). However, whether these changes are
      related to a subsequent decline in glomerular filtration rate (GFR) remains
      unclear. METHODS AND RESULTS: We enrolled totally 100 hypertensive out-patients
      with eGFR >= 30 mL/min/1.73 m(2). The mean annual rate of GFR decline (?GFR/y)
      was -1.49 +/- 3.26 mL/min/1.73 m(2) per year during the follow-up period (34 +/-
      6 months). Flow cytometry was used to assess circulating EPC (CD34(+)/KDR(+)) and
      EMP levels (CD31(+)/annexin V(+)) in peripheral blood. The ?GFR/y was correlated
      with the EMP to EPC ratio (r= -0.465, p<0.001), microalbuminuria (r= -0.329,
      p=0.001), and the Framingham risk score (r= -0.245, p=0.013). When we divided the
      patients into 4 groups according to the EMP to EPC ratio, there was an
      association between the EMP to EPC ratio and the DeltaGFR/y (mean DeltaGFR/y:
      0.08 +/- 3.04 vs. -0.50 +/- 2.84 vs. -1.25 +/- 2.49 vs. -4.42 +/- 2.82, p<0.001).
      Multivariate analysis indicated that increased EMP to EPC ratio is an independent
      predictor of DeltaeGFR/y. CONCLUSIONS: An increased circulating EMP to EPC ratio
      is associated with subsequent decline in GFR in hypertensive patients, which
      suggests endothelial damage with reduced vascular repair capacity may contribute
      to further deterioration of renal function in patients with hypertension.

PMID- 23874702
TI  - Functional coding variants in SLC6A15, a possible risk gene for major depression.
AB  - SLC6A15 is a neuron-specific neutral amino acid transporter that belongs to the
      solute carrier 6 gene family. This gene family is responsible for presynaptic re
      uptake of the majority of neurotransmitters. Convergent data from human studies,
      animal models and pharmacological investigations suggest a possible role of
      SLC6A15 in major depressive disorder. In this work, we explored potential
      functional variants in this gene that could influence the activity of the amino
      acid transporter and thus downstream neuronal function and possibly the risk for
      stress-related psychiatric disorders. DNA from 400 depressed patients and 400
      controls was screened for genetic variants using a pooled targeted re-sequencing
      approach. Results were verified by individual re-genotyping and validated non
      synonymous coding variants were tested in an independent sample (N = 1934). Nine
      variants altering the amino acid sequence were then assessed for their functional
      effects by measuring SLC6A15 transporter activity in a cellular uptake assay. In
      total, we identified 405 genetic variants, including twelve non-synonymous
      variants. While none of the non-synonymous coding variants showed significant
      differences in case-control associations, two rare non-synonymous variants were
      associated with a significantly increased maximal (3)H proline uptake as compared
      to the wildtype sequence. Our data suggest that genetic variants in the SLC6A15
      locus change the activity of the amino acid transporter and might thus influence
      its neuronal function and the risk for stress-related psychiatric disorders. As
      statistically significant association for rare variants might only be achieved in
      extremely large samples (N >70,000) functional exploration may shed light on
      putatively disease-relevant variants.

PMID- 23874703
TI  - Structural basis of the novel S. pneumoniae virulence factor, GHIP, a glycosyl
      hydrolase 25 participating in host-cell invasion.
AB  - Pathogenic bacteria produce a wide variety of virulence factors that are
      considered to be potential antibiotic targets. In this study, we report the
      crystal structure of a novel S. pneumoniae virulence factor, GHIP, which is a
      streptococcus-specific glycosyl hydrolase. This novel structure exhibits an
      alpha/beta-barrel fold that slightly differs from other characterized hydrolases.
      The GHIP active site, located at the negatively charged groove in the barrel, is
      very similar to the active site in known peptidoglycan hydrolases. Functionally,
      GHIP exhibited weak enzymatic activity to hydrolyze the PNP-(GlcNAc)5
      peptidoglycan by the general acid/base catalytic mechanism. Animal experiments
      demonstrated a marked attenuation of S. pneumoniae-mediated virulence in mice
      infected by DeltaGHIP-deficient strains, suggesting that GHIP functions as a
      novel S. pneumoniae virulence factor. Furthermore, GHIP participates in allowing
      S. pneumoniae to colonize the nasopharynx and invade host epithelial cells. Taken
      together, these findings suggest that GHIP can potentially serve as an antibiotic
      target to effectively treat streptococcus-mediated infection. 

PMID- 23874704
TI  - Prospecting environmental mycobacteria: combined molecular approaches reveal
      unprecedented diversity.
AB  - BACKGROUND: Environmental mycobacteria (EM) include species commonly found in
      various terrestrial and aquatic environments, encompassing animal and human
      pathogens in addition to saprophytes. Approximately 150 EM species can be
      separated into fast and slow growers based on sequence and copy number
      differences of their 16S rRNA genes. Cultivation methods are not appropriate for
      diversity studies; few studies have investigated EM diversity in soil despite
      their importance as potential reservoirs of pathogens and their hypothesized role
      in masking or blocking M. bovis BCG vaccine. METHODS: We report here the
      development, optimization and validation of molecular assays targeting the 16S
      rRNA gene to assess diversity and prevalence of fast and slow growing EM in
      representative soils from semi tropical and temperate areas. New primer sets were
      designed also to target uniquely slow growing mycobacteria and used with PCR
      DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. RESULTS:
      PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a
      high abundance of pyrosequencing reads and DGGE bands corresponded to M.
      moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing
      provided more comprehensive information; additional prevalent species included M.
      chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total
      Mycobacterium genus in the soil samples ranged from 2.3*10(7) to 2.7*10(8) gene
      targets g(-1); slow growers prevalence from 2.9*10(5) to 1.2*10(7) cells g(-1).
      CONCLUSIONS: This combined molecular approach enabled an unprecedented
      qualitative and quantitative assessment of EM across soil samples. Good
      concordance was found between methods and the bioinformatics analysis was
      validated by random resampling. Sequences from most pathogenic groups associated
      with slow growth were identified in extenso in all soils tested with a specific
      assay, allowing to unmask them from the Mycobacterium whole genus, in which, as
      minority members, they would have remained undetected.

PMID- 23874705
TI  - The loudness dependence of auditory evoked potentials (LDAEP) as an indicator of
      serotonergic dysfunction in patients with predominant schizophrenic negative
      symptoms.
AB  - Besides the influence of dopaminergic neurotransmission on negative symptoms in
      schizophrenia, there is evidence that alterations of serotonin (5-HT) system
      functioning also play a crucial role in the pathophysiology of these disabling
      symptoms. From post mortem and genetic studies on patients with negative symptoms
      a 5-HT dysfunction is documented. In addition atypical neuroleptics and some
      antidepressants improve negative symptoms via serotonergic action. So far no
      research has been done to directly clarify the association between the
      serotonergic functioning and the extent of negative symptoms. Therefore, we
      examined the status of brain 5-HT level in negative symptoms in schizophrenia by
      means of the loudness dependence of auditory evoked potentials (LDAEP). The LDAEP
      provides a well established and non-invasive in vivo marker of the central 5-HT
      activity. We investigated 13 patients with schizophrenia with predominant
      negative symptoms treated with atypical neuroleptics and 13 healthy age and
      gender matched controls with a 32-channel EEG. The LDAEP of the N1/P2 component
      was evaluated by dipole source analysis and single electrode estimation at Cz.
      Psychopathological parameters, nicotine use and medication were assessed to
      control for additional influencing factors. Schizophrenic patients showed
      significantly higher LDAEP in both hemispheres than controls. Furthermore, the
      LDAEP in the right hemisphere in patients was related to higher scores in scales
      assessing negative symptoms. A relationship with positive symptoms was not found.
      These data might suggest a diminished central serotonergic neurotransmission in
      patients with predominant negative symptoms. 

PMID- 23874706
TI  - The Antarctic krill Euphausia superba shows diurnal cycles of transcription under
      natural conditions.
AB  - BACKGROUND: Polar environments are characterized by extreme seasonal changes in
      day length, light intensity and spectrum, the extent of sea ice during the
      winter, and food availability. A key species of the Southern Ocean ecosystem, the
      Antarctic krill (Euphausia superba) has evolved rhythmic physiological and
      behavioral mechanisms to adapt to daily and seasonal changes. The molecular
      organization of the clockwork underlying these biological rhythms is,
      nevertheless, still only partially understood. METHODOLOGY/PRINCIPAL FINDINGS:
      The genome sequence of the Antarctic krill is not yet available. A normalized
      cDNA library was produced and pyrosequenced in the attempt to identify large
      numbers of transcripts. All available E. superba sequences were then assembled to
      create the most complete existing oligonucleotide microarray platform with a
      total of 32,217 probes. Gene expression signatures of specimens collected in the
      Ross Sea at five different time points over a 24-hour cycle were defined, and
      1,308 genes differentially expressed were identified. Of the corresponding
      transcripts, 609 showed a significant sinusoidal expression pattern; about 40% of
      these exibithed a 24-hour periodicity while the other 60% was characterized by a
      shorter (about 12-hour) rhythm. We assigned the differentially expressed genes to
      functional categories and noticed that those concerning translation, proteolysis,
      energy and metabolic process, redox regulation, visual transduction and stress
      response, which are most likely related to daily environmental changes, were
      significantly enriched. Two transcripts of peroxiredoxin, thought to represent
      the ancestral timekeeping system that evolved about 2.5 billion years ago, were
      also identified as were two isoforms of the EsRh1 opsin and two novel arrestin1
      sequences involved in the visual transduction cascade. CONCLUSIONS: Our work
      represents the first characterization of the krill diurnal transcriptome under
      natural conditions and provides a first insight into the genetic regulation of
      physiological changes, which occur around the clock during an Antarctic summer
      day.

PMID- 23874708
TI  - Nanoscale roughness and morphology affect the IsoElectric Point of titania
      surfaces.
AB  - We report on the systematic investigation of the role of surface nanoscale
      roughness and morphology on the charging behaviour of nanostructured titania
      (TiO2) surfaces in aqueous solutions. IsoElectric Points (IEPs) of surfaces have
      been characterized by direct measurement of the electrostatic double layer
      interactions between titania surfaces and the micrometer-sized spherical silica
      probe of an atomic force microscope in NaCl aqueous electrolyte. The use of a
      colloidal probe provides well-defined interaction geometry and allows effectively
      probing the overall effect of nanoscale morphology. By using supersonic cluster
      beam deposition to fabricate nanostructured titania films, we achieved a
      quantitative control over the surface morphological parameters. We performed a
      systematical exploration of the electrical double layer properties in different
      interaction regimes characterized by different ratios of characteristic
      nanometric lengths of the system: the surface rms roughness Rq, the correlation
      length xi and the Debye length lambdaD. We observed a remarkable reduction by
      several pH units of IEP on rough nanostructured surfaces, with respect to flat
      crystalline rutile TiO2. In order to explain the observed behavior of IEP, we
      consider the roughness-induced self-overlap of the electrical double layers as a
      potential source of deviation from the trend expected for flat surfaces. 

PMID- 23874709
TI  - Immunogenicity of two FMDV nonameric peptides encapsulated in liposomes in mice
      and the protective efficacy in guinea pigs.
AB  - It has been predicted that nonameric peptides I (VP1(26-34), RRQHTDVSF), II
      (VP1(157-165), RTLPTSFNY) and III (VP1(45-53), KEQVNVLDL) from the VP1 capsid
      protein of the foot-and-mouth disease virus (FMDV) are T cell epitopes. To
      investigate whether these peptides have immunological activity, BALB/c mice were
      immunized with peptide I, II or III conjugated with immunostimulating complexes
      (ISCOMs). A cytotoxic T lymphocyte assay was used to evaluate the cytotoxic
      activity induced by peptides along with by measuring peptide-specific T-cell
      proliferation and CD8(+) T lymphocyte numbers in whole blood and interferon (IFN)
      gamma production in peripheral blood mononuclear cells induced by peptides. To
      further identify the protective efficacy of peptides, an FMDV challenge assay was
      done in guinea pigs. Peptides I and II stimulated significant increases in T-cell
      proliferation, CD8(+) T lymphocytes, and IFN-gamma secretion and cytotoxic
      activity compared to controls. The FMDV challenge assay indicated peptides I and
      II can protect over 60% of animals from virus attack. The results demonstrate
      that peptides I and II encapsulated in liposomes should be CTL epitopes of FMDV
      and can protect animals from virus attack to some extent.

PMID- 23874707
TI  - Linkage between increased nociception and olfaction via a SCN9A haplotype.
AB  - BACKGROUND AND AIMS: Mutations reducing the function of Nav1.7 sodium channels
      entail diminished pain perception and olfactory acuity, suggesting a link between
      nociception and olfaction at ion channel level. We hypothesized that if such link
      exists, it should work in both directions and gain-of-function Nav1.7 mutations
      known to be associated with increased pain perception should also increase
      olfactory acuity. METHODS: SCN9A variants were assessed known to enhance pain
      perception and found more frequently in the average population. Specifically,
      carriers of SCN9A variants rs41268673C>A (P610T; n = 14) or rs6746030C>T (R1150W;
      n = 21) were compared with non-carriers (n = 40). Olfactory function was
      quantified by assessing odor threshold, odor discrimination and odor
      identification using an established olfactory test. Nociception was assessed by
      measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt
      mechanical pressure, heat and electrical stimuli). RESULTS: The number of carried
      alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was
      significantly associated with the comparatively highest olfactory threshold (0
      alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1), 1
      allele: 10.6+/-2.6 (n = 34), 2 alleles: 9.5+/-2.1 (n = 40)). The same SCN9A
      haplotype determined the pain threshold to blunt pressure stimuli (0 alleles:
      21.1 N/m(2), 1 allele: 29.8+/-10.4 N/m(2), 2 alleles: 33.5+/-10.2 N/m(2)).
      CONCLUSIONS: The findings established a working link between nociception and
      olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the
      known reduced olfaction and pain in loss-of-function mutations, a bidirectional
      genetic functional association between nociception and olfaction exists at Nav1.7
      level.

PMID- 23874710
TI  - Outcome comparison between laparoscopic and open appendectomy: evidence from a
      nationwide population-based study.
AB  - BACKGROUND: Mounting evidence supports the use of laparoscopic techniques for the
      treatment of simple appendicitis. However, most of the advantages of these
      techniques are of limited clinical relevance. This study compares the treatment
      outcomes of laparoscopic appendectomies and open appendectomies performed in
      Taiwan. METHODS: This study uses data from the 2007 to 2009 Taiwan National
      Health Insurance Research Database. The study sample included 65,339 patients,
      hospitalized with a discharge diagnosis of acute appendicitis (33.8% underwent
      laparoscopic appendectomy). A generalized estimated equation (GEE) was performed
      to explore the relationship between the use of laparoscopy and 30-day re
      admission. Hierarchical linear regressions were performed to examine the
      relationship between the use of laparoscopy, the length of stay (LOS), and the
      cost per discharge. RESULTS: A significantly lower proportion of patients
      undergoing laparoscopic appendectomies were re-admitted within 30 days of their
      index appendectomy, in comparison to patients undergoing open appendectomies
      (0.66% versus 1.925, p<0.001). Compared with patients undergoing open
      appendectomies, patients undergoing laparoscopic appendectomies had a shorter LOS
      (4.01 versus 5.33 days, p<0.001) and a higher cost per discharge (NT$40,554
      versus NT$38,509, p<0.001. In 2007, the average exchange rate was US$1=NT$31.0).
      GEE revealed that the odds ratio of 30-day readmission for patients undergoing
      laparoscopic appendectomy was 0.38 (95% CI=0.33-0.46) that of patients undergoing
      open appendectomies, after adjusting for surgeon, hospital, and patient
      characteristics, as well as for the clustering effect of particular surgeons and
      the propensity score. CONCLUSION: This study found that laparoscopic
      appendectomies had a lower 30-day re-admission rate, and a shorter LOS, but a
      slightly higher cost per discharge than open appendectomies.

PMID- 23874711
TI  - Comparison of profile similarity measures for genetic interaction networks.
AB  - Analysis of genetic interaction networks often involves identifying genes with
      similar profiles, which is typically indicative of a common function. While
      several profile similarity measures have been applied in this context, they have
      never been systematically benchmarked. We compared a diverse set of correlation
      measures, including measures commonly used by the genetic interaction community
      as well as several other candidate measures, by assessing their utility in
      extracting functional information from genetic interaction data. We find that the
      dot product, one of the simplest vector operations, outperforms most other
      measures over a large range of gene pairs. More generally, linear similarity
      measures such as the dot product, Pearson correlation or cosine similarity
      perform better than set overlap measures such as Jaccard coefficient. Similarity
      measures that involve L2-normalization of the profiles tend to perform better for
      the top-most similar pairs but perform less favorably when a larger set of gene
      pairs is considered or when the genetic interaction data is thresholded. Such
      measures are also less robust to the presence of noise and batch effects in the
      genetic interaction data. Overall, the dot product measure performs consistently
      among the best measures under a variety of different conditions and genetic
      interaction datasets. 

PMID- 23874712
TI  - PARTAKE survey of public knowledge and perceptions of clinical research in India.
AB  - BACKGROUND: A public that is an informed partner in clinical research is
      important for ethical, methodological, and operational reasons. There are
      indications that the public is unaware or misinformed, and not sufficiently
      engaged in clinical research but studies on the topic are lacking. PARTAKE -
      Public Awareness of Research for Therapeutic Advancements through Knowledge and
      Empowerment is a program aimed at increasing public awareness and partnership in
      clinical research. The PARTAKE Survey is a component of the program. OBJECTIVE:
      To study public knowledge and perceptions of clinical research. METHODS: A 40
      item questionnaire combining multiple-choice and open-ended questions was
      administered to 175 English- or Hindi-speaking individuals in 8 public locations
      representing various socioeconomic strata in New Delhi, India. RESULTS:
      Interviewees were 18-84 old (mean: 39.6, SD +/- 16.6), 23.6% female, 68.6%
      employed, 7.3% illiterate, 26.3% had heard of research, 2.9% had participated and
      58.9% expressed willingness to participate in clinical research. The following
      perceptions were reported (% true/% false/% not aware): 'research benefits
      society' (94.1%/3.5%/2.3%), 'the government protects against unethical clinical
      research' (56.7%/26.3%/16.9%), 'research hospitals provide better care'
      (67.2%/8.7%/23.9%), 'confidentiality is adequately protected'
      (54.1%/12.3%/33.5%), 'participation in research is voluntary' (85.3%/5.8%/8.7%);
      'participants treated like 'guinea pigs'' (20.7%/53.2%/26.0%), and 'compensation
      for participation is adequate' (24.7%/12.9%/62.3%). CONCLUSIONS: Results suggest
      the Indian public is aware of some key features of clinical research (e.g.,
      purpose, value, voluntary nature of participation), and supports clinical
      research in general but is unaware of other key features (e.g., compensation,
      confidentiality, protection of human participants) and exhibits some distrust in
      the conduct and reporting of clinical trials. Larger, cross-cultural surveys are
      required to inform educational programs addressing these issues.

PMID- 23874713
TI  - Ribosomal proteins RPL37, RPS15 and RPS20 regulate the Mdm2-p53-MdmX network.
AB  - Changes to the nucleolus, the site of ribosome production, have long been linked
      to cancer, and mutations in several ribosomal proteins (RPs) have been associated
      with an increased risk for cancer in human diseases. Relevantly, a number of RPs
      have been shown to bind to MDM2 and inhibit MDM2 E3 ligase activity, leading to
      p53 stabilization and cell cycle arrest, thus revealing a RP-Mdm2-p53 signaling
      pathway that is critical for ribosome biogenesis surveillance. Here, we have
      identified RPL37, RPS15, and RPS20 as RPs that can also bind Mdm2 and activate
      p53. We found that each of the aforementioned RPs, when ectopically expressed,
      can stabilize both co-expressed Flag-tagged Mdm2 and HA-tagged p53 in p53-null
      cells as well as endogenous p53 in a p53-containing cell line. For each RP, the
      mechanism of Mdm2 and p53 stabilization appears to be through inhibiting the E3
      ubiquitin ligase activity of Mdm2. Interestingly, although they are each capable
      of inducing cell death and cell cycle arrest, these RPs differ in the p53 target
      genes that are regulated upon their respective introduction into cells.
      Furthermore, each RP can downregulate MdmX levels but in distinct ways. Thus,
      RPL37, RPS15 and RPS20 regulate the Mdm2-p53-MdmX network but employ different
      mechanisms to do so. 

PMID- 23874714
TI  - Identification of highly selective and potent histone deacetylase 3 inhibitors
      using click chemistry-based combinatorial fragment assembly.
AB  - To find histone deacetylase 3 (HDAC3)-selective inhibitors, a series of 504
      candidates was assembled using "click chemistry", by reacting nine alkynes
      bearing a zinc-binding group with 56 azide building blocks in the presence of
      Cu(I) catalyst. Screening of the 504-member triazole library against HDAC3 and
      other HDAC isozymes led to the identification of potent and selective HDAC3
      inhibitors T247 and T326. These compounds showed potent HDAC3 inhibition with
      submicromolar IC50s, whereas they did not strongly inhibit other isozymes.
      Compounds T247 and T326 also induced a dose-dependent selective increase of NF
      kappaB acetylation in human colon cancer HCT116 cells, indicating selective
      inhibition of HDAC3 in the cells. In addition, these HDAC3-selective inhibitors
      induced growth inhibition of cancer cells, and activated HIV gene expression in
      latent HIV-infected cells. These findings indicate that HDAC3-selective
      inhibitors are promising candidates for anticancer drugs and antiviral agents.
      This work also suggests the usefulness of the click chemistry approach to find
      isozyme-selective HDAC inhibitors. 

PMID- 23874715
TI  - Intracellular delivery of lipopolysaccharide induces effective Th1-immune
      responses independent of IL-12.
AB  - Lipopolysaccharide (LPS) is responsible for many of the inflammatory responses
      and pathogenic effects of Gram-negative bacteria, however, it also induces
      protective immune responses. LPS induces the production of inflammatory cytokines
      such as TNF-alpha, IL-6, and IL-12 from dendritic cells (DCs) and macrophages. It
      is thought that IL-12 is required for one of the protective immune responses
      induced by LPS, the T helper 1 (Th1)-immune response, which include the
      production of IFN-gamma from Th1cells and IgG2c class switching. Here, we clearly
      demonstrate that intracellular delivery of LPS by LPS-formulated liposomes (LPS
      liposomes) does not induce the production of inflammatory cytokines from DCs, but
      enhances Th1-immune responses via type-I IFNs, independent of IL-12.
      Collectively, our results strongly suggest that LPS-liposomes can effectively
      induce Th1-immune responses without inducing unnecessary inflammation, and may be
      useful as an immune adjuvant to induce protective immunity. 

PMID- 23874716
TI  - Low incidence of miscarriage induced by the scent of male littermates of original
      mates: male kinship reduces the bruce effect in female mice, Mus musculus.
AB  - The scent of a novel male can elicit pregnancy block in recently mated female
      mice (Mus musculus), a phenomenon known as the Bruce effect. Despite abundant
      literature on the Bruce effect in rodents, it remains unclear whether males
      related to a female's original mate can induce the Bruce effect in out-bred,
      communally living mice. We investigated this question using Kunming (KM) male
      mice of varying genetic relatedness. Recently mated females were subjected to
      three treatments: exposure to the urine of the mate, urine of the mate's male
      littermate, and urine of a male unrelated to the mate. It was found that the
      urine of male littermates of the females' mates did not elicit more pregnancy
      block than that of the females' mates. However, the urine of novel males caused a
      higher rate of female miscarriage than that of the females' mates. By using a
      habituation-dishabituation paradigm, we found that unmated females could
      discriminate the urine scents of two male littermates from those of a novel male
      unrelated to the littermates. To understand how females use urinary cues to
      discriminate between males with different genetic relationships, we used gas
      chromatography coupled with mass spectrometry (GC-MS) to examine the volatile
      composition of urine from males with varying relatedness. It was found that KM
      male littermates shared similar volatile compositions in their urine. Our results
      suggest that male kinship reduces the Bruce effect in female KM mice, and provide
      additional evidence for mate choice being partly mediated by the Bruce effect in
      KM mice. 

PMID- 23874717
TI  - Multi-host expression system for recombinant production of challenging proteins.
AB  - Recombinant production of complex eukaryotic proteins for structural analyses
      typically requires a profound screening process to identify suitable constructs
      for the expression of ample amounts of properly folded protein. Furthermore, the
      evaluation of an optimal expression host has a major impact on protein yield and
      quality as well as on actual cost of the production process. Here we present a
      novel fast expression system for multiple hosts based on a single donor vector
      termed pFlp-Bac-to-Mam. The range of applications of pFlp-Bac-to-Mam comprises
      highly efficient transient transfection of HEK293-6E in serum-free suspension
      culture and subsequent large-scale production of challenging proteins expressing
      in mg per Liter level using either the baculoviral expression vector system or
      stable CHO production cell lines generated by Flp-mediated cassette exchange. The
      success of the multi-host expression vector to identify the optimal expression
      strategy for efficient production of high quality protein is demonstrated in a
      comparative expression study of three model proteins representing different
      protein classes: intracellular expression using a fluorescent protein, secretion
      of a single-chain-Fv-hIgG1Fc fusion construct and production of a large amount of
      highly homogeneous protein sample of the extracellular domain of a Toll-like
      receptor. The evaluation of the production efficiency shows that the pFlp-Bac-to
      Mam system allows a fast and individual optimization of the expression strategy
      for each protein class. 

PMID- 23874718
TI  - Are high-impact species predictable? An analysis of naturalised grasses in
      northern Australia.
AB  - Predicting which species are likely to cause serious impacts in the future is
      crucial for targeting management efforts, but the characteristics of such species
      remain largely unconfirmed. We use data and expert opinion on tropical and
      subtropical grasses naturalised in Australia since European settlement to
      identify naturalised and high-impact species and subsequently to test whether
      high-impact species are predictable. High-impact species for the three main
      affected sectors (environment, pastoral and agriculture) were determined by
      assessing evidence against pre-defined criteria. Twenty-one of the 155
      naturalised species (14%) were classified as high-impact, including four that
      affected more than one sector. High-impact species were more likely to have
      faster spread rates (regions invaded per decade) and to be semi-aquatic. Spread
      rate was best explained by whether species had been actively spread (as pasture),
      and time since naturalisation, but may not be explanatory as it was tightly
      correlated with range size and incidence rate. Giving more weight to minimising
      the chance of overlooking high-impact species, a priority for biosecurity, meant
      a wider range of predictors was required to identify high-impact species, and the
      predictive power of the models was reduced. By-sector analysis of predictors of
      high impact species was limited by their relative rarity, but showed sector
      differences, including to the universal predictors (spread rate and habitat) and
      life history. Furthermore, species causing high impact to agriculture have
      changed in the past 10 years with changes in farming practice, highlighting the
      importance of context in determining impact. A rationale for invasion ecology is
      to improve the prediction and response to future threats. Although our study
      identifies some universal predictors, it suggests improved prediction will
      require a far greater emphasis on impact rather than invasiveness, and will need
      to account for the individual circumstances of affected sectors and the relative
      rarity of high-impact species. 

PMID- 23874719
TI  - Landscape movements of Anopheles gambiae malaria vector mosquitoes in rural
      Gambia.
AB  - BACKGROUND: For malaria control in Africa it is crucial to characterise the
      dispersal of its most efficient vector, Anopheles gambiae, in order to target
      interventions and assess their impact spatially. Our study is, we believe, the
      first to present a statistical model of dispersal probability against distance
      from breeding habitat to human settlements for this important disease vector.
      METHODS/PRINCIPAL FINDINGS: We undertook post-hoc analyses of mosquito catches
      made in The Gambia to derive statistical dispersal functions for An. gambiae
      sensu lato collected in 48 villages at varying distances to alluvial larval
      habitat along the River Gambia. The proportion dispersing declined exponentially
      with distance, and we estimated that 90% of movements were within 1.7 km.
      Although a 'heavy-tailed' distribution is considered biologically more plausible
      due to active dispersal by mosquitoes seeking blood meals, there was no
      statistical basis for choosing it over a negative exponential distribution. Using
      a simple random walk model with daily survival and movements previously recorded
      in Burkina Faso, we were able to reproduce the dispersal probabilities observed
      in The Gambia. CONCLUSIONS/SIGNIFICANCE: Our results provide an important
      quantification of the probability of An. gambiae s.l. dispersal in a rural
      African setting typical of many parts of the continent. However, dispersal will
      be landscape specific and in order to generalise to other spatial configurations
      of habitat and hosts it will be necessary to produce tractable models of mosquito
      movements for operational use. We show that simple random walk models have
      potential. Consequently, there is a pressing need for new empirical studies of
      An. gambiae survival and movements in different settings to drive this
      development.

PMID- 23874720
TI  - Genome-wide identification, phylogeny and expression profile of vesicle fusion
      components in Verticillium dahliae.
AB  - Vesicular trafficking plays a crucial role in protein localization and movement,
      signal transduction, and multiple developmental processes in eukaryotic cells.
      Vesicle fusion is the final and key step in vesicle-mediated trafficking and
      mainly relies on SNAREs (soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors), the regulators including SM (Sec1/Munc18) family proteins,
      Rab GTPases and exocyst subunits. Verticillium dahliae is a widespread soil
      fungus that causes disruptive vascular diseases on a wide range of plants. To
      date, no genes involved in vesicular fusion process have been identified and
      characterized in V. dahliae. The recent publication of the draft genome sequence
      of V. dahliae allowed us to conduct a genome-wide identification, phylogeny and
      expression profile of genes encoding vesicular fusion components. Using compared
      genomics and phylogenetic methods, we identified 44 genes encoding vesicle fusion
      components in the V. dahliae genome. According to the structural features of
      their encoded proteins, the 44 V. dahliae genes were classified into 22 SNAREs (6
      Qa-, 4 Qb-, 6 Qc-, 1 Qbc- and 5 R-types), 4 SM family proteins, 10 Rab GTPases
      and 8 exocyst proteins. Based on phylogeny and motif constitution analysis,
      orthologs of vesicle fusion component in filamentous fungi were generally
      clustered together into the same subclasses with well-supported bootstrap values.
      Analysis of the expression profiles of these genes indicated that many of them
      are significantly differentially expressed during vegetative growth and
      microsclerotia formation in V. dahliae. The analysis show that many components of
      vesicle fusion are well conserved in filamentous fungi and indicate that vesicle
      fusion plays a critical role in microsclerotia formation of smoke tree wilt
      fungus V. dahliae. The genome-wide identification and expression analysis of
      components involved in vesicle fusion should facilitate research in this gene
      family and give new insights toward elucidating their functions in growth,
      development and pathogenesis of V. dahliae. 

PMID- 23874721
TI  - Amyloid-like fibril elongation follows michaelis-menten kinetics.
AB  - A number of proteins can aggregate into amyloid-like fibrils. It was noted that
      fibril elongation has similarities to an enzymatic reaction, where monomers or
      oligomers would play a role of substrate and nuclei/fibrils would play a role of
      enzyme. The question is how similar these processes really are. We obtained
      experimental data on insulin amyloid-like fibril elongation at the conditions
      where other processes which may impact kinetics of fibril formation are minor and
      fitted it using Michaelis-Menten equation. The correlation of the fit is very
      good and repeatable. It speaks in favour of enzyme-like model of fibril
      elongation. In addition, obtained [Formula: see text] and [Formula: see text]
      values at different conditions may help in better understanding influence of
      environmental factors on the process of fibril elongation. 

PMID- 23874722
TI  - Effects of nasal or pulmonary delivered treatments with an adenovirus vectored
      interferon (mDEF201) on respiratory and systemic infections in mice caused by
      cowpox and vaccinia viruses.
AB  - An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201)
      was evaluated for efficacy against lethal cowpox (Brighton strain) and vaccinia
      (WR strain) virus respiratory and systemic infections in mice. Two routes of
      mDEF201 administration were used, nasal sinus (5-ul) and pulmonary (50-ul), to
      compare differences in efficacy, since the preferred treatment of humans would be
      in a relatively small volume delivered intranasally. Lower respiratory infections
      (LRI), upper respiratory infections (URI), and systemic infections were induced
      by 50-ul intranasal, 10-ul intranasal, and 100-ul intraperitoneal virus
      challenges, respectively. mDEF201 treatments were given prophylactically either
      24 h (short term) or 56d (long-term) prior to virus challenge. Single nasal sinus
      treatments of 10(6) and 10(7) PFU/mouse of mDEF201 protected all mice from
      vaccinia-induced LRI mortality (comparable to published studies with pulmonary
      delivered mDEF201). Systemic vaccinia infections responded significantly better
      to nasal sinus delivered mDEF201 than to pulmonary treatments. Cowpox LRI
      infections responded to 10(7) mDEF201 treatments, but a 10(6) dose was only
      weakly protective. Cowpox URI infections were equally treatable by nasal sinus
      and pulmonary delivered mDEF201 at 10(7) PFU/mouse. Dose-responsive prophylaxis
      with mDEF201, given one time only 56 d prior to initiating a vaccinia virus LRI
      infection, was 100% protective from 10(5) to 10(7) PFU/mouse. Improvements in
      lung hemorrhage score and lung weight were evident, as were decreases in liver,
      lung, and spleen virus titers. Thus, mDEF201 was able to treat different vaccinia
      and cowpox virus infections using both nasal sinus and pulmonary treatment
      regimens, supporting its development for humans. 

PMID- 23874723
TI  - Hepatitis B virus s protein enhances sperm apoptosis and reduces sperm
      fertilizing capacity in vitro.
AB  - OBJECTIVE: Studying the impact of Hepatitis B virus S protein (HBs) on early
      apoptotic events in human spermatozoa and sperm fertilizing capacity.
      METHODOLOGY/PRINCIPAL FINDINGS: Spermatozoa were exposed to HBs (0, 25, 50, 100
      ug/ml) for 3 h, and then fluo-4 AM calcium assay, Calcein/Co(2+) assay, protein
      extraction and ELISA, ADP/ATP ratio assay, sperm motility and hyperactivation and
      sperm-zona pellucida (ZP) binding and ZP-induced acrosome reaction (ZPIAR) tests
      were performed. The results showed that in the spermatozoa, with increasing
      concentration of HBs, (1) average cytosolic free Ca(2+) concentration ([Ca(2+)]i)
      rose; (2) fluorescence intensity of Cal-AM declined; (3) average levels of
      cytochrome c decreased in mitochondrial fraction and increased in cytosolic
      fraction; (4) ADP/ATP ratios rose; (5) average rates of total motility and mean
      hyperactivation declined; (6) average rate of ZPIAR declined. In the above groups
      the effects of HBs exhibited dose dependency. However, there was no significant
      difference in the number of sperms bound to ZP between the control and all test
      groups. CONCLUSION: HBs could induce early events in the apoptotic cascade in
      human spermatozoa, such as elevation of [Ca(2+)]i, opening of mitochondrial
      permeability transition pore (MPTP), release of cytochrome c (cyt c) and increase
      of ADP/ATP ratio, but exerted a negative impact on sperm fertilizing capacity.

PMID- 23874724
TI  - KCNE1 rs1805127 polymorphism increases the risk of atrial fibrillation: a meta
      analysis of 10 studies.
AB  - BACKGROUND: Atrial fibrillation (AF) is one of the most common types of
      arrhythmia in humans. Recently, many studies have investigated the relationship
      between human atrial fibrillation and the single nucleotide polymorphism (SNP) of
      rs1805127 (A>G) in KCNE1 gene, but the results were still inconsistent and
      inconclusive. METHOD: Electronic databases and bibliographies of retrieved
      studies were searched. We performed a meta-analysis of ten case-control studies,
      including 2099 cases and 2252 controls, to evaluate the association of rs1805127
      polymorphism (A>G) with the risk of AF. Random-effects model was used when the
      heterogeneity was obvious; otherwise, fixed-effects model was applied. Meta
      regression was performed to examine potential source of heterogeneity. Egger's
      test and Begg's test were used to detect publication biases. RESULTS: The results
      showed a significantly increased risk of AF in homozygote comparison (GG vs.
      AA:OR = 1.899, 95%CI: 1.568, 2.300; Pheterogeneity = 0.217), heterozygote
      comparison (GA vs. AA:OR = 1.436, 95% CI:1.190, 1.732; Pheterogeneity = 0.739),
      dominant model(GA /GG vs. AA: OR = 1.624, 95%CI: 1.361, 1.938; Pheterogeneity =
      0.778) and recessive model (GG vs. GA/AA: OR = 1.394, 95%CI:1.152, 1.686;
      Pheterogeneity = 0.03). Meta-regression revealed that the sample size and the
      types of AF were the source of the heterogeneity. CONCLUSION: The rs1805127
      polymorphism (A>G) of KCNE1 is associated with an increased risk of AF, which
      suggests the rs1805217 polymorphism of KCNE1 gene may play an important role in
      the pathogenesis of AF.

PMID- 23874725
TI  - Differential regulation of human 3beta-hydroxysteroid dehydrogenase type 2 for
      steroid hormone biosynthesis by starvation and cyclic AMP stimulation: studies in
      the human adrenal NCI-H295R cell model.
AB  - Human steroid biosynthesis depends on a specifically regulated cascade of enzymes
      including 3beta-hydroxysteroid dehydrogenases (HSD3Bs). Type 2 HSD3B catalyzes
      the conversion of pregnenolone, 17alpha-hydroxypregnenolone and
      dehydroepiandrosterone to progesterone, 17alpha-hydroxyprogesterone and
      androstenedione in the human adrenal cortex and the gonads but the exact
      regulation of this enzyme is unknown. Therefore, specific downregulation of
      HSD3B2 at adrenarche around age 6-8 years and characteristic upregulation of
      HSD3B2 in the ovaries of women suffering from the polycystic ovary syndrome
      remain unexplained prompting us to study the regulation of HSD3B2 in adrenal NCI
      H295R cells. Our studies confirm that the HSD3B2 promoter is regulated by
      transcription factors GATA, Nur77 and SF1/LRH1 in concert and that the NBRE/Nur77
      site is crucial for hormonal stimulation with cAMP. In fact, these three
      transcription factors together were able to transactivate the HSD3B2 promoter in
      placental JEG3 cells which normally do not express HSD3B2. By contrast,
      epigenetic mechanisms such as methylation and acetylation seem not involved in
      controlling HSD3B2 expression. Cyclic AMP was found to exert differential effects
      on HSD3B2 when comparing short (acute) versus long-term (chronic) stimulation.
      Short cAMP stimulation inhibited HSD3B2 activity directly possibly due to
      regulation at co-factor or substrate level or posttranslational modification of
      the protein. Long cAMP stimulation attenuated HSD3B2 inhibition and increased
      HSD3B2 expression through transcriptional regulation. Although PKA and MAPK
      pathways are obvious candidates for possibly transmitting the cAMP signal to
      HSD3B2, our studies using PKA and MEK1/2 inhibitors revealed no such downstream
      signaling of cAMP. However, both signaling pathways were clearly regulating
      HSD3B2 expression. 

PMID- 23874726
TI  - Transcriptome of extracellular vesicles released by hepatocytes.
AB  - The discovery that the cells communicate through emission of vesicles has opened
      new opportunities for better understanding of physiological and pathological
      mechanisms. This discovery also provides a novel source for non-invasive disease
      biomarker research. Our group has previously reported that hepatocytes release
      extracellular vesicles with protein content reflecting the cell-type of origin.
      Here, we show that the extracellular vesicles released by hepatocytes also carry
      RNA. We report the messenger RNA composition of extracellular vesicles released
      in two non-tumoral hepatic models: primary culture of rat hepatocytes and a
      progenitor cell line obtained from a mouse foetal liver. We describe different
      subpopulations of extracellular vesicles with different densities and protein and
      RNA content. We also show that the RNA cargo of extracellular vesicles released
      by primary hepatocytes can be transferred to rat liver stellate-like cells and
      promote their activation. Finally, we provide in vitro and in vivo evidence that
      liver-damaging drugs galactosamine, acetaminophen, and diclofenac modify the RNA
      content of these vesicles. To summarize, we show that the extracellular vesicles
      secreted by hepatocytes contain various RNAs. These vesicles, likely to be
      involved in the activation of stellate cells, might become a new source for non
      invasive identification of the liver toxicity markers. 

PMID- 23874727
TI  - High levels of S100A8/A9 proteins aggravate ventilator-induced lung injury via
      TLR4 signaling.
AB  - BACKGROUND: Bacterial products add to mechanical ventilation in enhancing lung
      injury. The role of endogenous triggers of innate immunity herein is less well
      understood. S100A8/A9 proteins are released by phagocytes during inflammation.
      The present study investigates the role of S100A8/A9 proteins in ventilator
      induced lung injury. METHODS: Pulmonary S100A8/A9 levels were measured in samples
      obtained from patients with and without lung injury. Furthermore, wild-type and
      S100A9 knock-out mice, naive and with lipopolysaccharide-induced injured lungs,
      were randomized to 5 hours of spontaneously breathing or mechanical ventilation
      with low or high tidal volume (VT). In addition, healthy spontaneously breathing
      and high VT ventilated mice received S100A8/A9, S100A8 or vehicle intratracheal.
      Furthermore, the role of Toll-like receptor 4 herein was investigated. RESULTS:
      S100A8/A9 protein levels were elevated in patients and mice with lung injury.
      S100A8/A9 levels synergistically increased upon the lipopolysaccharide/high VT MV
      double hit. Markers of alveolar barrier dysfunction, cytokine and chemokine
      levels, and histology scores were attenuated in S100A9 knockout mice undergoing
      the double-hit. Exogenous S100A8/A9 and S100A8 induced neutrophil influx in
      spontaneously breathing mice. In ventilated mice, these proteins clearly
      amplified inflammation: neutrophil influx, cytokine, and chemokine levels were
      increased compared to ventilated vehicle-treated mice. In contrast,
      administration of S100A8/A9 to ventilated Toll-like receptor 4 mutant mice did
      not augment inflammation. CONCLUSION: S100A8/A9 proteins increase during lung
      injury and contribute to inflammation induced by HVT MV combined with
      lipopolysaccharide. In the absence of lipopolysaccharide, high levels of
      extracellular S100A8/A9 still amplify ventilator-induced lung injury via Toll
      like receptor 4.

PMID- 23874728
TI  - Exogenous and endogenous hormones in relation to glioma in women: a meta-analysis
      of 11 case-control studies.
AB  - BACKGROUND AND OBJECTIVE: Previous investigations of glioma risk in women have
      focused on oral contraceptive (OC), hormone replacement therapy (HRT), and
      reproductive factors. However, the results of published studies were inconclusive
      and inconsistent. Thus, a meta-analysis based on published case-control studies
      was performed to assess the role of exogenous and endogenous hormones factors in
      glioma risk. METHODS: The PubMed and EMBASE databases were searched without any
      restrictions on language or publication year. Reference lists from retrieved
      articles were also reviewed. We included case-control studies reporting relative
      risks (RRs) with corresponding 95% confidence intervals (CIs) (or data to
      calculate them) between oral contraceptive (OC) and hormone replacement therapy
      (HRT) use, reproductive factors and glioma. Random-effects models were used to
      calculate the summary risk estimates. RESULTS: Finally, 11 eligible studies with
      4860 cases and 14,740 controls were identified. A lower risk of glioma was
      observed among women who were ever users of exogenous hormones (OC RR = 0.707,
      95% CI = 0.604-0.828; HRT: RR = 0.683, 95% CI = 0.577-0.808) compared with never
      users. An increased glioma risk was associated with older age at menarche (RR =
      1.401, 95% CI = 1.052-1.865). No association was observed for menopause status,
      parous status, age at menopause, or age at first birth and glioma risk.
      CONCLUSION: The results of our study support the hypothesis female sex hormones
      play a role in the development of glioma in women. Additional studies are
      warranted to validate the conclusion from this meta-analysis and clarity the
      underlying mechanisms.

PMID- 23874729
TI  - TLM-Quant: an open-source pipeline for visualization and quantification of gene
      expression heterogeneity in growing microbial cells.
AB  - Gene expression heterogeneity is a key driver for microbial adaptation to
      fluctuating environmental conditions, cell differentiation and the evolution of
      species. This phenomenon has therefore enormous implications, not only for life
      in general, but also for biotechnological applications where unwanted
      subpopulations of non-producing cells can emerge in large-scale fermentations.
      Only time-lapse fluorescence microscopy allows real-time measurements of gene
      expression heterogeneity. A major limitation in the analysis of time-lapse
      microscopy data is the lack of fast, cost-effective, open, simple and adaptable
      protocols. Here we describe TLM-Quant, a semi-automatic pipeline for the analysis
      of time-lapse fluorescence microscopy data that enables the user to visualize and
      quantify gene expression heterogeneity. Importantly, our pipeline builds on the
      open-source packages ImageJ and R. To validate TLM-Quant, we selected three
      possible scenarios, namely homogeneous expression, highly 'noisy' heterogeneous
      expression, and bistable heterogeneous expression in the Gram-positive bacterium
      Bacillus subtilis. This bacterium is both a paradigm for systems-level studies on
      gene expression and a highly appreciated biotechnological 'cell factory'. We
      conclude that the temporal resolution of such analyses with TLM-Quant is only
      limited by the numbers of recorded images. 

PMID- 23874730
TI  - Urogenital Chlamydia trachomatis infections among ethnic groups in Paramaribo,
      Suriname; determinants and ethnic sexual mixing patterns.
AB  - BACKGROUND: Little is known about the epidemiology of urogenital Chlamydia
      trachomatis infection (chlamydia) in Suriname. Suriname is a society composed of
      many ethnic groups, such as Creoles, Maroons, Hindustani, Javanese, Chinese,
      Caucasians, and indigenous Amerindians. We estimated determinants for chlamydia,
      including the role of ethnicity, and identified transmission patterns and ethnic
      sexual networks among clients of two clinics in Paramaribo, Suriname. METHODS:
      Participants were recruited at two sites a sexually transmitted infections (STI)
      clinic and a family planning (FP) clinic in Paramaribo. Urine samples from men
      and nurse-collected vaginal swabs were obtained for nucleic acid amplification
      testing. Logistic regression analysis was used to identify determinants of
      chlamydia. Multilocus sequence typing (MLST) was performed to genotype C.
      trachomatis. To identify transmission patterns and sexual networks, a minimum
      spanning tree was created, using full MLST profiles. Clusters in the minimum
      spanning tree were compared for ethnic composition. RESULTS: Between March 2008
      and July 2010, 415 men and 274 women were included at the STI clinic and 819
      women at the FP clinic. Overall chlamydia prevalence was 15% (224/1508). Age,
      ethnicity, and recruitment site were significantly associated with chlamydia in
      multivariable analysis. Participants of Creole and Javanese ethnicity were more
      frequently infected with urogenital chlamydia. Although sexual mixing with other
      ethnic groups did differ significantly per ethnicity, this mixing was not
      independently significantly associated with chlamydia. We typed 170 C.
      trachomatis-positive samples (76%) and identified three large C. trachomatis
      clusters. Although the proportion from various ethnic groups differed
      significantly between the clusters (P = 0.003), all five major ethnic groups were
      represented in all three clusters. CONCLUSION: Chlamydia prevalence in Suriname
      is high and targeted prevention measures are required. Although ethnic sexual
      mixing differed between ethnic groups, differences in prevalence between ethnic
      groups could not be explained by sexual mixing.

PMID- 23874731
TI  - Infections in children admitted with complicated severe acute malnutrition in
      Niger.
AB  - BACKGROUND: Although malnutrition affects thousands of children throughout the
      Sahel each year and predisposes them to infections, there is little data on the
      etiology of infections in these populations. We present a clinical and biological
      characterization of infections in hospitalized children with complicated severe
      acute malnutrition (SAM) in Maradi, Niger. METHODS: Children with complicated SAM
      hospitalized in the intensive care unit of a therapeutic feeding center, with no
      antibiotics in the previous 7 days, were included. A clinical examination, blood,
      urine and stool cultures, and chest radiography were performed systematically on
      admission. RESULTS: Among the 311 children included in the study, gastroenteritis
      was the most frequent clinical diagnosis on admission, followed by respiratory
      tract infections and malaria. Blood or urine culture was positive in 17% and 16%
      of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria
      were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty
      nine (9%) children died, most frequently from sepsis. Clinical signs were poor
      indicators of infection and initial diagnoses correlated poorly with biologically
      or radiography-confirmed diagnoses. CONCLUSIONS: These data confirm the high
      level of infections and poor correlation with clinical signs in children with
      complicated SAM, and provide antibiotic resistance profiles from an area with
      limited microbiological data. These results contribute unique data to the ongoing
      debate on the use and choice of broad-spectrum antibiotics as first-line
      treatment in children with complicated SAM and reinforce the call for an update
      of international guidelines on management of complicated SAM based on more recent
      data.

PMID- 23874732
TI  - Characterization of virulence properties in the C. parapsilosis sensu lato
      species.
AB  - The C. parapsilosis sensu lato group involves three closely related species, C.
      parapsilosis sensu stricto, C. orthopsilosis and C. metapsilosis. Although their
      overall clinical importance is dramatically increasing, there are few studies
      regarding the virulence properties of the species of the psilosis complex. In
      this study, we tested 63 C. parapsilosis sensu stricto, 12 C. metapsilosis and 18
      C. orthopsilosis isolates for the ability to produce extracellular proteases,
      secrete lipases and form pseudohyphae. Significant differences were noted between
      species, with the C. metapsilosis strains failing to secrete lipase or to produce
      pseudohyphae. Nine different clinical isolates each of C. parapsilosis sensu
      stricto, C. orthopsilosis and C. metapsilosis were co-cultured with immortalized
      murine or primary human macrophages. C. parapsilosis sensu stricto isolates
      showed a significantly higher resistance to killing by primary human macrophages
      compared to C. orthopsilosis and C. metapsilosis isolates. In contrast, the
      killing of isolates by J774.2 mouse macrophages did not differ significantly
      between species. However, C. parapsilosis sensu stricto isolates induced the most
      damage to murine and human macrophages, and C. metapsilosis strains were the
      least toxic. Furthermore, strains that produced lipase or pseudohyphae were most
      resistant to macrophage-mediated killing and produced the most cellular damage.
      Finally, we used 9 isolates of each of the C. parapsilosis sensus lato species to
      examine their impact on the survival of Galleriamellonella larvae. The mortality
      rate of G. mellonella larvae infected with C. metapsilosis isolates was
      significantly lower than those infected with C. parapsilosis sensu stricto or C.
      orthopsilosis strains. Taken together, our findings demonstrate that C.
      metapsilosis is indeed the least virulent member of the psilosis group, and also
      highlight the importance of pseudohyphae and secreted lipases during fungal-host
      interactions. 

PMID- 23874733
TI  - Response variance in functional maps: neural darwinism revisited.
AB  - The mechanisms by which functional maps and map plasticity contribute to cortical
      computation remain controversial. Recent studies have revisited the theory of
      neural Darwinism to interpret the learning-induced map plasticity and neuronal
      heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian
      principle provides a substrate to explain the relationship between neuron
      heterogeneity and cortical functional maps. We demonstrate in the rat auditory
      cortex that the degree of response variance is closely correlated with the size
      of its representational area. Further, we show that the response variance within
      a given population is altered through training. These results suggest that larger
      representational areas may help to accommodate heterogeneous populations of
      neurons. Thus, functional maps and map plasticity are likely to play essential
      roles in Darwinian computation, serving as effective, but not absolutely
      necessary, structures to generate diverse response properties within a neural
      population. 

PMID- 23874734
TI  - Milk fat content and DGAT1 genotype determine lipid composition of the milk fat
      globule membrane.
AB  - During secretion of milk fat globules, triacylglycerol (TAG) droplets are
      enveloped by a phospholipid (PL) trilayer. Globule size has been found to be
      related to polar lipid composition and fat content, and milk fat content and
      fatty acid composition have been associated with the diacylglycerol
      acyltransferase 1 (DGAT1) K232A polymorphism; however, the association between
      the DGAT1 polymorphism and fat globule size and polar lipid composition has not
      been studied. The ratio between polar and neutral lipids as well as the
      composition of the polar lipids in milk has industrial as well as nutritional and
      health implications. Understanding phenotypic and genotypic factors influencing
      these parameters could contribute to improving milk lipid composition for dairy
      products. The focus of the present study was to determine the effect of both fat
      content and DGAT1 polymorphism on PL/TAG ratio, as a marker for milk fat globule
      size, and detailed PL composition. Milk samples were selected from 200 cows such
      that there were equal numbers of samples for the different fat contents as well
      as per DGAT1 genotype. Samples were analyzed for neutral and polar lipid
      concentration and composition. PL/TAG ratio was significantly associated with
      both fat content and DGAT1 genotype. Phosphatidylinositol and phosphatidylserine
      concentrations were associated with fat content*DGAT1 genotype with a stronger
      association for the AA than the KK genotype. Sphingomyelin concentration tended
      to interact with fat content*DGAT1 genotype. Phosphatidylethanolamine (PE)
      concentration showed a biphasic response to fat content, suggesting that multiple
      biological processes influence its concentration. These results provide a new
      direction for controlling polar lipid concentration and composition in milk
      through selective breeding of cows. 

PMID- 23874735
TI  - Heritable and precise zebrafish genome editing using a CRISPR-Cas system.
AB  - We have previously reported a simple and customizable CRISPR (clustered regularly
      interspaced short palindromic repeats) RNA-guided Cas9 nuclease (RGN) system that
      can be used to efficiently and robustly introduce somatic indel mutations in
      endogenous zebrafish genes. Here we demonstrate that RGN-induced mutations are
      heritable, with efficiencies of germline transmission reaching as high as 100%.
      In addition, we extend the power of the RGN system by showing that these
      nucleases can be used with single-stranded oligodeoxynucleotides (ssODNs) to
      create precise intended sequence modifications, including single nucleotide
      substitutions. Finally, we describe and validate simple strategies that improve
      the targeting range of RGNs from 1 in every 128 basepairs (bps) of random DNA
      sequence to 1 in every 8 bps. Together, these advances expand the utility of the
      CRISPR-Cas system in the zebrafish beyond somatic indel formation to heritable
      and precise genome modifications. 

PMID- 23874736
TI  - Ratio of trunk to leg volume as a new body shape metric for diabetes and
      mortality.
AB  - BACKGROUND: Body shape is a known risk factor for diabetes and mortality, but the
      methods estimating body shape, BMI and waist circumference are crude. We
      determined whether a novel body shape measure, trunk to leg volume ratio, was
      independently associated with diabetes and mortality. METHODS: Data from the
      National Health and Nutritional Examination Survey 1999-2004, a study
      representative of the US population, were used to generate dual-energy X-ray
      absorptiometry-derived trunk to leg volume ratio and determine its associations
      to diabetes, metabolic covariates, and mortality by BMI category, gender, and
      race/ethnicity group. RESULTS: The prevalence of pre-diabetes and diabetes
      increased with age, BMI, triglycerides, blood pressure, and decreased HDL level.
      After adjusting for covariates, the corresponding fourth to first quartile trunk
      to leg volume ratio odds ratios (OR) were 6.8 (95% confidence interval [CI], 4.9
      9.6) for diabetes, 3.9 (95% CI, 3.0-5.2) for high triglycerides, 1.8 (95% CI, 1.6
      2.1) for high blood pressure, 3.0 (95% CI, 2.4-3.8) for low HDL, 3.6 (95% CI, 2.8
      4.7) for metabolic syndrome, and 1.76 (95% CI, 1.20-2.60) for mortality.
      Additionally, trunk to leg volume ratio was the strongest independent measure
      associated with diabetes (P<0.001), even after adjusting for BMI and waist
      circumference. Even among those with normal BMI, those in the highest quartile of
      trunk to leg volume ratio had a higher likelihood of death (5.5%) than those in
      the lowest quartile (0.2%). Overall, trunk to leg volume ratio is driven by
      competing mechanisms of changing adiposity and lean mass. CONCLUSIONS: A high
      ratio of trunk to leg volume showed a strong association to diabetes and
      mortality that was independent of total and regional fat distributions. This
      novel body shape measure provides additional information regarding central
      adiposity and appendicular wasting to better stratify individuals at risk for
      diabetes and mortality, even among those with normal BMI.

PMID- 23874737
TI  - Using energetic models to investigate the survival and reproduction of beaked
      whales (family Ziphiidae).
AB  - Mass stranding of several species of beaked whales (family Ziphiidae) associated
      with exposure to anthropogenic sounds has raised concern for the conservation of
      these species. However, little is known about the species' life histories, prey
      or habitat requirements. Without this knowledge, it becomes difficult to assess
      the effects of anthropogenic sound, since there is no way to determine whether
      the disturbance is impacting the species' physical or environmental requirements.
      Here we take a bioenergetics approach to address this gap in our knowledge, as
      the elusive, deep-diving nature of beaked whales has made it hard to study these
      effects directly. We develop a model for Ziphiidae linking feeding energetics to
      the species' requirements for survival and reproduction, since these life history
      traits would be the most likely to be impacted by non-lethal disturbances. Our
      models suggest that beaked whale reproduction requires energy dense prey, and
      that poor resource availability would lead to an extension of the inter-calving
      interval. Further, given current information, it seems that some beaked whale
      species require relatively high quality habitat in order to meet their
      requirements for survival and reproduction. As a result, even a small non-lethal
      disturbance that results in displacement of whales from preferred habitats could
      potentially impact a population if a significant proportion of that population
      was affected. We explored the impact of varying ecological parameters and model
      assumptions on survival and reproduction, and find that calf and fetus survival
      appear more readily affected than the survival of adult females. 

PMID- 23874738
TI  - Does recall after sleep-dependent memory consolidation reinstate sensitivity to
      retroactive interference?
AB  - Previous studies have shown that newly encoded memories are more resistant to
      retroactive interference when participants are allowed to sleep after learning
      the original material, suggesting a sleep-related strengthening of memories. In
      the present study, we investigated delayed, long-term effects of sleep vs. sleep
      deprivation (SD) on the first post-training night on memory consolidation and
      resistance to interference. On day 1, participants learned a list of unrelated
      word pairs (AB), either in the morning or in the evening, then spent the post
      training night in a sleep or sleep deprivation condition, in a within-subject
      paradigm. On day 4, at the same time of day, they learned a novel list of word
      pairs (AC) in which 50% of the word pairs stemmed with the same word than in the
      AB list, resulting in retroactive interference. Participants had then to recall
      items from the AB list upon presentation of the "A" stem. Recall was marginally
      improved in the evening, as compared to the morning learning group. Most
      importantly, retroactive interference effects were found in the sleep evening
      group only, contrary to the hypothesis that sleep exerts a protective role
      against intrusion by novel but similar learning. We tentatively suggest that
      these results can be explained in the framework of the memory reconsolidation
      theory, stating that exposure to similar information sets back consolidated items
      in a labile form again sensitive to retroactive interference. In this context,
      sleep might not protect against interference but would promote an update of
      existing episodic memories while preventing saturation of the memory network due
      to the accumulation of dual traces. 

PMID- 23874739
TI  - The innate immune response in HIV/AIDS septic shock patients: a comparative
      study.
AB  - INTRODUCTION: In recent years, the incidence of sepsis has increased in
      critically ill HIV/AIDS patients, and the presence of severe sepsis emerged as a
      major determinant of outcomes in this population. The inflammatory response and
      deregulated cytokine production play key roles in the pathophysiology of sepsis;
      however, these mechanisms have not been fully characterized in HIV/AIDS septic
      patients. METHODS: We conducted a prospective cohort study that included HIV/AIDS
      and non-HIV patients with septic shock. We measured clinical parameters and
      biomarkers (C-reactive protein and cytokine levels) on the first day of septic
      shock and compared these parameters between HIV/AIDS and non-HIV patients.
      RESULTS: We included 30 HIV/AIDS septic shock patients and 30 non-HIV septic
      shock patients. The HIV/AIDS patients presented low CD4 cell counts (72 [7-268]
      cells/mm(3)), and 17 (57%) patients were on HAART before hospital admission. Both
      groups were similar according to the acute severity scores and hospital
      mortality. The IL-6, IL-10 and G-CSF levels were associated with hospital
      mortality in the HIV/AIDS septic group; however, the CRP levels and the
      surrogates of innate immune activation (cytokines) were similar among HIV/AIDS
      and non-HIV septic patients. Age (odds ratio 1.05, CI 95% 1.02-1.09, p=0.002) and
      the IL-6 levels (odds ratio 1.00, CI 95% 1.00-1.01, p=0.05) were independent risk
      factors for hospital mortality. CONCLUSIONS: IL-6, IL-10 and G-CSF are biomarkers
      that can be used to predict prognosis and outcomes in HIV/AIDS septic patients.
      Although HIV/AIDS patients are immunocompromised, an innate immune response can
      be activated in these patients, which is similar to that in the non-HIV septic
      population. In addition, age and the IL-6 levels are independent risk factors for
      hospital mortality irrespective of HIV/AIDS disease.

PMID- 23874740
TI  - Antiplatelet/anticoagulant agents and chronic subdural hematoma in the elderly.
AB  - BACKGROUND AND PURPOSE: In the last decade there has been an increasing use of
      antiplatelet/anticoagulant agents in the elderly. The aim of the study was to
      evaluate the association between exposure to anticoagulant/antiplatelet therapy
      and chronic subdural haematoma-CSDH. METHODS: Single institution case-control
      study involving 138786 patients older than 60 years who visited our academic
      tertiary care Emergency Department from January 1st 2001 to December 31st 2010.
      345 patients with CSDH (cases) were identified by review of ICD-9 codes 432.1 and
      852.2x. Case and controls were matched with a 1:3 ratio for gender, age (+/- 5
      years), year of admission and recent trauma. A conditional logistic model was
      built. A stratified analysis was performed with respect to the presence (842
      patients) or absence (536 patients) of recent trauma. RESULTS: There were 345
      cases and 1035 controls. Both anticoagulant and antiplatelet agents were
      associated with an increased risk of CSDH with an OR of 2.46 (CI 95% 1.66-3.64)
      and 1.42 (CI 95% 1.07-1.89), respectively. OR was 2.70 (CI 95% 1.75-4.15), 1.90
      (CI 95% 1.13-3.20), and 1.37(CI 95% 0.99-1.90) for patients receiving oral
      anticoagulants, ADP-antagonists, or Cox-inhibitors, respectively. History of
      recent trauma was an effect modifier of the association between anticoagulants
      and CSDH, with an OR 1.71 (CI 95% 0.99-2.96) for patients with history of trauma
      and 4.30 (CI 95% 2.23-8.32) for patients without history of trauma. CONCLUSIONS:
      Anticoagulant and antiplatelet therapy have a significant association with an
      increased risk of CSDH. This association, for patients under anticoagulant
      therapy, appears even stronger in those patients who develop a CSDH in the
      absence of a recent trauma.

PMID- 23874742
TI  - Hepatitis C virus non-structural protein 3 interacts with cytosolic 5'(3')
      deoxyribonucleotidase and partially inhibits its activity.
AB  - Infection with hepatitis C virus (HCV) is etiologically involved in liver
      cirrhosis, hepatocellular carcinoma and B-cell lymphomas. It has been
      demonstrated previously that HCV non-structural protein 3 (NS3) is involved in
      cell transformation. In this study, a yeast two-hybrid screening experiment was
      conducted to identify cellular proteins interacting with HCV NS3 protein.
      Cytosolic 5'(3')-deoxyribonucleotidase (cdN, dNT-1) was found to interact with
      HCV NS3 protein. Binding domains of HCV NS3 and cellular cdN proteins were also
      determined using the yeast two-hybrid system. Interactions between HCV NS3 and
      cdN proteins were further demonstrated by co-immunoprecipitation and confocal
      analysis in cultured cells. The cellular cdN activity was partially repressed by
      NS3 protein in both the transiently-transfected and the stably-transfected
      systems. Furthermore, HCV partially repressed the cdN activity while had no
      effect on its protein expression in the systems of HCV sub-genomic replicons and
      infectious HCV virions. Deoxyribonucleotidases are present in most mammalian
      cells and involve in the regulation of intracellular deoxyribonucleotides pools
      by substrate cycles. Control of DNA precursor concentration is essential for the
      maintenance of genetic stability. Reduction of cdN activity would result in the
      imbalance of DNA precursor concentrations. Thus, our results suggested that HCV
      partially reduced the cdN activity via its NS3 protein and this may in turn cause
      diseases. 

PMID- 23874741
TI  - An analysis of pregnancy-related mortality in the KEMRI/CDC health and
      demographic surveillance system in western Kenya.
AB  - BACKGROUND: Pregnancy-related (PR) deaths are often a result of direct obstetric
      complications occurring at childbirth. METHODS AND FINDINGS: To estimate the
      burden of and characterize risk factors for PR mortality, we evaluated deaths
      that occurred between 2003 and 2008 among women of childbearing age (15 to 49
      years) using Health and Demographic Surveillance System data in rural western
      Kenya. WHO ICD definition of PR mortality was used: "the death of a woman while
      pregnant or within 42 days of termination of pregnancy, irrespective of the cause
      of death". In addition, symptoms and events at the time of death were examined
      using the WHO verbal autopsy methodology. Deaths were categorized as either (i)
      directly PR: main cause of death was ascribed as obstetric, or (ii) indirectly
      PR: main cause of death was non-obstetric. Of 3,223 deaths in women 15 to 49
      years, 249 (7.7%) were PR. One-third (34%) of these were due to direct obstetric
      causes, predominantly postpartum hemorrhage, abortion complications and puerperal
      sepsis. Two-thirds were indirect; three-quarters were attributable to human
      immunodeficiency virus (HIV/AIDS), malaria and tuberculosis. Significantly more
      women who died in lower socio-economic groups sought care from traditional birth
      attendants (p = 0.034), while less impoverished women were more likely to seek
      hospital care (p = 0.001). The PR mortality ratio over the six years was 740 (95%
      CI 651-838) per 100,000 live births, with no evidence of reduction over time
      (chi(2) linear trend = 1.07; p = 0.3). CONCLUSIONS: These data supplement current
      scanty information on the relationship between infectious diseases and poor
      maternal outcomes in Africa. They indicate low uptake of maternal health
      interventions in women dying during pregnancy and postpartum, suggesting improved
      access to and increased uptake of skilled obstetric care, as well as preventive
      measures against HIV/AIDS, malaria and tuberculosis among all women of
      childbearing age may help to reduce pregnancy-related mortality.

PMID- 23874743
TI  - Characterization of vascular disease risk in postmenopausal women and its
      association with cognitive performance.
AB  - OBJECTIVES: While global measures of cardiovascular (CV) risk are used to guide
      prevention and treatment decisions, these estimates fail to account for the
      considerable interindividual variability in pre-clinical risk status. This study
      investigated heterogeneity in CV risk factor profiles and its association with
      demographic, genetic, and cognitive variables. METHODS: A latent profile analysis
      was applied to data from 727 recently postmenopausal women enrolled in the Kronos
      Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within
      three years of their last menstrual period, and free of current or past CV
      disease. Education level, apolipoprotein E epsilon4 allele (APOE4), ethnicity,
      and age were modeled as predictors of latent class membership. The association
      between class membership, characterizing CV risk profiles, and performance on
      five cognitive factors was examined. A supervised random forest algorithm with a
      10-fold cross-validation estimator was used to test accuracy of CV risk
      classification. RESULTS: The best-fitting model generated two distinct phenotypic
      classes of CV risk 62% of women were "low-risk" and 38% "high-risk". Women
      classified as low-risk outperformed high-risk women on language and mental
      flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029).
      Women with a college degree or above were more likely to be in the low-risk class
      (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the
      probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012;
      respectively). The prevalence rate of APOE-epsilon4 was higher in the high-risk
      class compared with rates in the low-risk class. CONCLUSION: Among recently
      menopausal women, significant heterogeneity in CV risk is associated with
      education level, age, ethnicity, and genetic indicators. The model-based latent
      classes were also associated with cognitive function. These differences may point
      to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could
      in turn clarify preclinical disease, and screening and preventive strategies.
      ClinicalTrials.gov NCT00154180.

PMID- 23874744
TI  - Yin Yang gene expression ratio signature for lung cancer prognosis.
AB  - Many studies have established gene expression-based prognostic signatures for
      lung cancer. All of these signatures were built from training data sets by
      learning the correlation of gene expression with the patients' survival time.
      They require all new sample data to be normalized to the training data,
      ultimately resulting in common problems of low reproducibility and
      impracticality. To overcome these problems, we propose a new signature model
      which does not involve data training. We hypothesize that the imbalance of two
      opposing effects in lung cancer cells, represented by Yin and Yang genes,
      determines a patient's prognosis. We selected the Yin and Yang genes by comparing
      expression data from normal lung and lung cancer tissue samples using both
      unsupervised clustering and pathways analyses. We calculated the Yin and Yang
      gene expression mean ratio (YMR) as patient risk scores. Thirty-one Yin and
      thirty-two Yang genes were identified and selected for the signature development.
      In normal lung tissues, the YMR is less than 1.0; in lung cancer cases, the YMR
      is greater than 1.0. The YMR was tested for lung cancer prognosis prediction in
      four independent data sets and it significantly stratified patients into high-
      and low-risk survival groups (p = 0.02, HR = 2.72; p = 0.01, HR = 2.70; p =
      0.007, HR = 2.73; p = 0.005, HR = 2.63). It also showed prediction of the
      chemotherapy outcomes for stage II & III. In multivariate analysis, the YMR risk
      factor was more successful at predicting clinical outcomes than other commonly
      used clinical factors, with the exception of tumor stage. The YMR can be measured
      in an individual patient in the clinic independent of gene expression platform.
      This study provided a novel insight into the biology of lung cancer and shed
      light on the clinical applicability. 

PMID- 23874745
TI  - Impairment in task-specific modulation of muscle coordination correlates with the
      severity of hand impairment following stroke.
AB  - Significant functional impairment of the hand is commonly observed in stroke
      survivors. Our previous studies suggested that the inability to modulate muscle
      coordination patterns according to task requirements may be substantial after
      stroke, but these limitations have not been examined directly. In this study, we
      aimed to characterize post-stroke impairment in the ability to modulate muscle
      coordination patterns across tasks and its correlation with hand impairment.
      Fourteen stroke survivors, divided into a group with severe hand impairment (8
      subjects) and a group with moderate hand impairment (6 subjects) according to
      their clinical functionality score, participated in the experiment. Another four
      neurologically intact subjects participated in the experiment to serve as a point
      of comparison. Activation patterns of nine hand and wrist muscles were recorded
      using surface electromyography while the subjects performed six isometric tasks.
      Patterns of covariation in muscle activations across tasks, i.e., muscle modules,
      were extracted from the muscle activation data. Our results showed that the
      degree of reduction in the inter-task separation of the multi-muscle activation
      patterns was indicative of the clinical functionality score of the subjects (mean
      value = 26.2 for severely impaired subjects, 38.1 for moderately impaired
      subjects). The values for moderately impaired subjects were much closer to those
      of the impaired subjects (mean value = 46.1). The number of muscle modules
      extracted from the muscle activation patterns of a subject across six tasks,
      which represents the degree of motor complexity, was found to be correlated with
      the clinical functionality score (R = 0.68). Greater impairment was also
      associated with a change in the muscle module patterns themselves, with greater
      muscle coactivation. A substantial reduction in the degrees-of-freedom of the
      multi-muscle coordination post-stroke was apparent, and the extent of the
      reduction, assessed by the stated metrics, was strongly associated with the level
      of clinical impairment.

PMID- 23874746
TI  - Differential gene expression in response to Papaya ringspot virus infection in
      Cucumis metuliferus using cDNA-amplified fragment length polymorphism analysis.
AB  - A better understanding of virus resistance mechanisms can offer more effective
      strategies to control virus diseases. Papaya ringspot virus (PRSV), Potyviridae,
      causes severe economical losses in papaya and cucurbit production worldwide.
      However, no resistance gene against PRSV has been identified to date. This study
      aimed to identify candidate PRSV resistance genes using cDNA-AFLP analysis and
      offered an open architecture and transcriptomic method to study those transcripts
      differentially expressed after virus inoculation. The whole genome expression
      profile of Cucumis metuliferus inoculated with PRSV was generated using cDNA
      amplified fragment length polymorphism (cDNA-AFLP) method. Transcript derived
      fragments (TDFs) identified from the resistant line PI 292190 may represent genes
      involved in the mechanism of PRSV resistance. C. metuliferus susceptible Acc.
      2459 and resistant PI 292190 lines were inoculated with PRSV and subsequently
      total RNA was isolated for cDNA-AFLP analysis. More than 400 TDFs were expressed
      specifically in resistant line PI 292190. A total of 116 TDFs were cloned and
      their expression patterns and putative functions in the PRSV-resistance mechanism
      were further characterized. Subsequently, 28 out of 116 candidates which showed
      two-fold higher expression levels in resistant PI 292190 than those in
      susceptible Acc. 2459 after virus inoculation were selected from the reverse
      northern blot and bioinformatic analysis. Furthermore, the time point expression
      profiles of these candidates by northern blot analysis suggested that they might
      play roles in resistance against PRSV and could potentially provide valuable
      information for controlling PRSV disease in the future. 

PMID- 23874747
TI  - Morphological and proteomic responses of Eruca sativa exposed to silver
      nanoparticles or silver nitrate.
AB  - Silver nanoparticles (AgNPs) are widely used in commercial products, and there
      are growing concerns about their impact on the environment. Information about the
      molecular interaction of AgNPs with plants is lacking. To increase our
      understanding of the mechanisms involved in plant responses to AgNPs and to
      differentiate between particle specific and ionic silver effects we determined
      the morphological and proteomic changes induced in Eruca sativa (commonly called
      rocket) in response to AgNPs or AgNO3. Seedlings were treated for 5 days with
      different concentrations of AgNPs or AgNO3. A similar increase in root elongation
      was observed when seedlings were exposed to 10 mg Ag L(1) of either PVP-AgNPs or
      AgNO3. At this concentration we performed electron microscopy investigations and
      2-dimensional electrophoresis (2DE) proteomic profiling. The low level of overlap
      of differentially expressed proteins indicates that AgNPs and AgNO3 cause
      different plant responses. Both Ag treatments cause changes in proteins involved
      in the redox regulation and in the sulfur metabolism. These responses could play
      an important role to maintain cellular homeostasis. Only the AgNP exposure cause
      the alteration of some proteins related to the endoplasmic reticulum and vacuole
      indicating these two organelles as targets of the AgNPs action. These data add
      further evidences that the effects of AgNPs are not simply due to the release of
      Ag ions. 

PMID- 23874748
TI  - miR-379 regulates cyclin B1 expression and is decreased in breast cancer.
AB  - MicroRNAs are small non-coding RNA molecules that control gene expression post
      transcriptionally, and are known to be altered in many diseases including breast
      cancer. The aim of this study was to determine the relevance of miR-379 in breast
      cancer. miR-379 expression was quantified in clinical samples including tissues
      from breast cancer patients (n=103), healthy controls (n=30) and patients with
      benign breast disease (n=35). The level of miR-379 and its putative target Cyclin
      B1 were investigated on all breast tissue specimens by RQ-PCR. Potential
      relationships with gene expression and patient clinicopathological details were
      also determined. The effect of miR-379 on Cyclin B1 protein expression and
      function was investigated using western blot, immunohistochemistry and
      proliferation assays respectively. Finally, the levels of circulating miR-379
      were determined in whole blood from patients with breast cancer (n=40) and
      healthy controls (n=34). The level of miR-379 expression was significantly
      decreased in breast cancer (Mean(SEM) 1.9 (0.09) Log10 Relative Quantity (RQ))
      compared to normal breast tissues (2.6 (0.16) Log10 RQ, p<0.01). miR-379 was also
      found to decrease significantly with increasing tumour stage. A significant
      negative correlation was determined between miR-379 and Cyclin B1 (r=-0.31,
      p<0.001). Functional assays revealed reduced proliferation (p<0.05) and decreased
      Cyclin B1 protein levels following transfection of breast cancer cells with miR
      379. Circulating miR-379 was not significantly dysregulated in patients with
      breast cancer compared to healthy controls (p=0.42). This data presents miR-379
      as a novel regulator of Cyclin B1 expression, with significant loss of the miRNA
      observed in breast tumours. 

PMID- 23874749
TI  - The host-encoded Heme Regulated Inhibitor (HRI) facilitates virulence-associated
      activities of bacterial pathogens.
AB  - Here we show that cells lacking the heme-regulated inhibitor (HRI) are highly
      resistant to infection by bacterial pathogens. By examining the infection process
      in wild-type and HRI null cells, we found that HRI is required for pathogens to
      execute their virulence-associated cellular activities. Specifically, unlike wild
      type cells, HRI null cells infected with the gram-negative bacterial pathogen
      Yersinia are essentially impervious to the cytoskeleton-damaging effects of the
      Yop virulence factors. This effect is due to reduced functioning of the Yersinia
      type 3 secretion (T3S) system which injects virulence factors directly into the
      host cell cytosol. Reduced T3S activity is also observed in HRI null cells
      infected with the bacterial pathogen Chlamydia which results in a dramatic
      reduction in its intracellular proliferation. We go on to show that a HRI
      mediated process plays a central role in the cellular infection cycle of the Gram
      positive pathogen Listeria. For this pathogen, HRI is required for the post
      invasion trafficking of the bacterium to the infected host cytosol. Thus by
      depriving Listeria of its intracellular niche, there is a highly reduced
      proliferation of Listeria in HRI null cells. We provide evidence that these
      infection-associated functions of HRI (an eIF2alpha kinase) are independent of
      its activity as a regulator of protein synthesis. This is the first report of a
      host factor whose absence interferes with the function of T3S secretion and
      cytosolic access by pathogens and makes HRI an excellent target for inhibitors
      due to its broad virulence-associated activities. 

PMID- 23874750
TI  - Inhibition of VEGF-C modulates distal lymphatic remodeling and secondary
      metastasis.
AB  - Tumor-associated lymphatics are postulated to provide a transit route for
      disseminating metastatic cells. This notion is supported by preclinical findings
      that inhibition of pro-lymphangiogenic signaling during tumor development reduces
      cell spread to sentinel lymph nodes (SLNs). However, it is unclear how lymphatics
      downstream of SLNs contribute to metastatic spread into distal organs, or if
      modulating distal lymph transport impacts disease progression. Utilizing murine
      models of metastasis, longitudinal in vivo imaging of lymph transport, and
      function blocking antibodies against two VEGF family members, we provide evidence
      that distal lymphatics undergo disease course-dependent up-regulation of lymph
      transport coincidental with structural remodeling. Inhibition of VEGF-C activity
      with antibodies against VEGF-C or NRP2 prevented these disease-associated
      changes. Furthermore, utilizing a novel model of adjuvant treatment, we
      demonstrate that antagonism of VEGF-C or NRP2 decreases post SLN metastasis.
      These data support a potential therapeutic strategy for inhibiting distant
      metastatic dissemination via targeting tumor-associated lymphatic remodeling. 

PMID- 23874751
TI  - Effect of larvae treated with mixed biopesticide Bacillus thuringiensis-abamectin
      on sex pheromone communication system in cotton bollworm, Helicoverpa armigera.
AB  - Third instar larvae of the cotton bollworm (Helicoverpa armigera) were reared
      with artificial diet containing a Bacillus thuringiensis-abamectin (BtA)
      biopesticide mixture that resulted in 20% mortality (LD20). The adult male
      survivors from larvae treated with BtA exhibited a higher percentage of
      "orientation" than control males but lower percentages of "approaching" and
      "landing" in wind tunnel bioassays. Adult female survivors from larvae treated
      with BtA produced higher sex pheromone titers and displayed a lower calling
      percentage than control females. The ratio of Z-11-hexadecenal (Z11-16:Ald) and Z
      9-hexadecenal (Z9-16:Ald) in BtA-treated females changed and coefficients of
      variation (CV) of Z11-16:Ald and Z9-16:Ald were expanded compared to control
      females. The peak circadian calling time of BtA-treated females occurred later
      than that of control females. In mating choice experiment, both control males and
      BtA-treated males preferred to mate with control females and a portion of the Bt
      A treated males did not mate whereas all control males did. Our Data support that
      treatment of larvae with BtA had an effect on the sex pheromone communication
      system in surviving H. armigera moths that may contribute to assortative mating.

PMID- 23874752
TI  - Amelioration of liver injury by continuously targeted intervention against
      TNFRp55 in rats with acute-on-chronic liver failure.
AB  - BACKGROUND: Acute-on-chronic liver failure (ACLF) is an acute deterioration of
      established liver disease. Blocking the TNF (tumor necrosis factor)/TNFR (tumor
      necrosis factor receptor) 1 pathway may reduce hepatocyte apoptosis/necrosis, and
      subsequently decrease mortality during development of ACLF. We demonstrated that
      a long-acting TNF antagonist (soluble TNF receptor: IgG Fc [sTNFR:IgG-Fc])
      prevented/reduced development of acute liver failure by blocking the TNF/TNFR1
      (TNFRp55) pathway. However, it is still unclear if sTNFR:IgG-Fc can inhibit
      hepatocyte damage during development of ACLF. METHODOLOGY: Chronic liver disease
      (liver fibrosis/cirrhosis) was induced in Wistar rats by repeatedly challenging
      with human serum albumin (HSA), and confirmed by histopathology. ACLF was induced
      with D-galactosamine (D-GalN)/lipopolysaccharide (LPS) i.p. in the rats with
      chronic liver disease. Serum and liver were collected for biochemical,
      pathological and molecular biological examinations. PRINCIPAL FINDINGS: Reduced
      mortality was observed in sTNFR:IgG-Fc treated ACLF rats, consistent with reduced
      interleukin (IL)-6 levels in serum and liver, as well as reduced hepatic caspase
      3 activity, compared to that of mock treated group. Reduced hepatic damage was
      confirmed with histopathology in the sTNFR:IgG-Fc treated group, which is
      consistent with reduced Bcl-2 and Bax, at mRNA and protein levels, but increased
      hepatocyte proliferation (PCNA). This is also supported by the findings that
      caspase-3 production was up-regulated significantly in ACLF group compared to the
      mock treated group. Moreover, up-regulated caspase-3 was inhibited following
      sTNFR:IgG-Fc treatment. Finally, there was up-regulation of hepatic IL-22R in
      sTNFR:IgG-Fc treated ACLF rats. CONCLUSIONS: sTNFR:IgG-Fc improved survival rate
      during development of ACLF via ameliorating liver injury with a potential
      therapeutic value.

PMID- 23874753
TI  - Super resolution microscopy reveals that caveolin-1 is required for spatial
      organization of CRFB1 and subsequent antiviral signaling in zebrafish.
AB  - Understanding spatial distribution and dynamics of receptors within unperturbed
      membranes is essential for elucidating their role in antiviral signaling, but
      conventional studies of detergent-resistant membrane fractions cannot provide
      this information. Caveolae are integral to numerous signaling pathways and these
      membrane domains have been previously implicated in viral entry but not antiviral
      defense. This study shows, for the first time, the importance of spatio-temporal
      regulation of signaling receptors and the importance of the regulation of
      clustering for downstream signaling. A novel mechanism for virus evasion of host
      cell defenses is demonstrated through disruption of clusters of signaling
      molecules organized within caveolin-rich domains. Viral infection leads to a
      downregulation in Caveolin-1b (Cav-1b), disrupting clusters of CRFB1, a zebrafish
      type I interferon receptor (-R) subunit. Super-resolution microscopy has enabled
      the first single-molecule imaging of CRFB1 association with cav-1b-containing
      membrane domains. Strikingly, downregulation of Cav-1b, the major protein
      component of caveolae, caused CRFB1 clusters to disperse. Dispersal of CRFB1
      clusters led to a suppressed antiviral immune response both in vitro and in vivo,
      through abrogation of downstream signaling. This response strongly suggests that
      CRFB1 organization within cav-1b-containing membrane domains is critical for IFN
      mediated antiviral defense and presents a previously undescribed antiviral
      evasion strategy to alter IFN signaling and the antiviral immune response. 

PMID- 23874754
TI  - Influenza vaccine effectiveness against hospitalisation with confirmed influenza
      in the 2010-11 seasons: a test-negative observational study.
AB  - Immunisation programs are designed to reduce serious morbidity and mortality from
      influenza, but most evidence supporting the effectiveness of this intervention
      has focused on disease in the community or in primary care settings. We aimed to
      examine the effectiveness of influenza vaccination against hospitalisation with
      confirmed influenza. We compared influenza vaccination status in patients
      hospitalised with PCR-confirmed influenza with patients hospitalised with
      influenza-negative respiratory infections in an Australian sentinel surveillance
      system. Vaccine effectiveness was estimated from the odds ratio of vaccination in
      cases and controls. We performed both simple multivariate regression and a
      stratified analysis based on propensity score of vaccination. Vaccination status
      was ascertained in 333 of 598 patients with confirmed influenza and 785 of 1384
      test-negative patients. Overall estimated crude vaccine effectiveness was 57%
      (41%, 68%). After adjusting for age, chronic comorbidities and pregnancy status,
      the estimated vaccine effectiveness was 37% (95% CI: 12%, 55%). In an analysis
      accounting for a propensity score for vaccination, the estimated vaccine
      effectiveness was 48.3% (95% CI: 30.0, 61.8%). Influenza vaccination was
      moderately protective against hospitalisation with influenza in the 2010 and 2011
      seasons. 

PMID- 23874755
TI  - A pig model of the preterm neonate: anthropometric and physiological
      characteristics.
AB  - BACKGROUND: Large animal models are an essential tool in the development of
      rationally-based new clinical therapies for preterm infants. We provide a
      description of the newborn pig as a model of the preterm neonate in terms of
      growth parameters, physiology and the requirement for intensive care over a range
      of gestational ages. METHODS: Twenty-nine litters of piglets (n = 298) were
      delivered by caesarean section at six timepoints during gestation from 91d to
      113d (term = 115d). Two groups, at 91 and 97d gestation, also received maternal
      glucocorticoid treatment. At four of these timepoints, piglets (n = 79) were
      ventilated, sedated and monitored using standard neonatal intensive care
      techniques for up to 8 h in various experimental protocols. RESULTS: Body weight
      increased from mean 697 g (SD 193) at 91d gestation to 1331 g (SD 368) at 113d
      gestation. Piglets delivered at 97d gestation were able to be resuscitated and
      kept alive for at least 8 h on respiratory support after surfactant
      administration. Maternal glucocorticoid treatment 48 h and 24 h hours prior to
      delivery reduced the requirement for ventilator support and improved
      cardiovascular stability. CONCLUSION: The pig provides a relevant model for the
      study of human preterm physiology and for investigation of novel therapies to
      improve outcomes.

PMID- 23874756
TI  - Identification of a novel sulfonamide non-nucleoside reverse transcriptase
      inhibitor by a phenotypic HIV-1 full replication assay.
AB  - Classical target-based, high-throughput screening has been useful for the
      identification of inhibitors for known molecular mechanisms involved in the HIV
      life cycle. In this study, the development of a cell-based assay that uses a
      phenotypic drug discovery approach based on automated high-content screening is
      described. Using this screening approach, the antiviral activity of 26,500 small
      molecules from a relevant chemical scaffold library was evaluated. Among the
      selected hits, one sulfonamide compound showed strong anti-HIV activity against
      wild-type and clinically relevant multidrug resistant HIV strains. The
      biochemical inhibition, point resistance mutations and the activity of structural
      analogs allowed us to understand the mode of action and propose a binding model
      for this compound with HIV-1 reverse transcriptase. 

PMID- 23874757
TI  - Electrospun poly(L-lactide) fiber with ginsenoside rg3 for inhibiting scar
      hyperplasia of skin.
AB  - Hypertrophic scarring (HS) has been considered as a great concern for patients
      and a challenging problem for clinicians as it can be cosmetically disfiguring
      and functionally debilitating. In this study, Ginsenoside Rg3/Poly(l-lactide) (G
      Rg3/PLLA) electrospun fibrous scaffolds covering on the full-thickness skin
      excisions location was designed to suppress the hypertrophic scar formation in
      vivo. SEM and XRD results indicated that the crystal G-Rg3 carried in PLLA
      electrospun fibers was in amorphous state, which facilitates the solubility of G
      Rg3 in the PLLA electrospun fibrous scaffolds, and solubility of G-Rg3 in PBS is
      increased from 3.2 ug/ml for pure G-Rg3 powders to 19.4 ug/ml for incorporated in
      PLLA-10% fibers. The released G-Rg3 content in the physiological medium could be
      further altered from 324 to 3445 ug in a 40-day release period by adjusting the G
      Rg3 incorporation amount in PLLA electrospun fibers. In vitro results
      demonstrated that electrospun G-Rg3/PLLA fibrous scaffold could significantly
      inhibit fibroblast cell growth and proliferation. In vivo results confirmed that
      the G-Rg3/PLLA electrospun fibrous scaffold showed significant improvements in
      terms of dermis layer thickness, fibroblast proliferation, collagen fibers and
      microvessels, revealing that the incorporation of the G-Rg3 in the fibers
      prevented the HS formation. The above results demonstrate the potential use of G
      Rg3/PLLA electrospun fibrous scaffolds to rapidly minimize fibroblast growth and
      restore the structural and functional properties of wounded skin for patients
      with deep trauma, severe burn injury, and surgical incision. 

PMID- 23874758
TI  - Lifelong caloric restriction increases working memory in mice.
AB  - Caloric restriction (CR) is argued to positively affect general health, longevity
      and the normally occurring age-related reduction of cognition. This issue is well
      examined, but most studies investigated the effect of short-term periods of CR.
      Herein, 4 weeks old female mice were fed caloric restricted for 4, 20 and
      especially for 74 weeks. CR mice received 60% of food eaten by their ad libitum
      (AL) fed littermates, and all age-matched groups were behaviorally analyzed. The
      motor coordination, which was tested by rotarod/accelerod, decreased age-related,
      but was not influenced by the different periods of CR. In contrast, the age
      related impairment of spontaneous locomotor activity and anxiety, both being
      evaluated by open field and by elevated plus maze test, was found aggravated by a
      lifelong CR. Measurement of cognitive performance with morris water maze showed
      that the working memory decreased age-related in AL mice, while a lifelong CR
      caused a better cognitive performance and resulted in a significantly better
      spatial memory upon 74 weeks CR feeding. However, a late-onset CR feeding in 66
      weeks old mice did not ameliorate the working memory. Therefore, a lifelong CR
      seems to be necessary to improve working memory. 

PMID- 23874759
TI  - Factors affecting harp seal (Pagophilus groenlandicus) strandings in the
      Northwest Atlantic.
AB  - The effects of climate change on high latitude regions are becoming increasingly
      evident, particularly in the rapid decline of sea ice cover in the Arctic. Many
      high latitude species dependent on sea ice are being forced to adapt to changing
      habitats. Harp seals (Pagophilus groenlandicus) are an indicator species for
      changing high-latitude ecosystems. This study analyzed multiple factors including
      ice cover, demographics, and genetic diversity, which could affect harp seal
      stranding rates along the eastern coast of the United States. Ice cover
      assessments were conducted for the month of February in the Gulf of St. Lawrence
      whelping region from 1991-2010 using remote sensing data, and harp seal stranding
      data were collected over the same time period. Genetic diversity, which may
      affect how quickly species can adapt to changing climates, was assessed using ten
      microsatellite markers to determine mean d (2) in a subset of stranded and by
      caught (presumably healthy) seals sampled along the northeast U.S. coast. Our
      study found a strong negative correlation (R (2) = 0.49) between ice cover in the
      Gulf of St. Lawrence and yearling harp seal strandings, but found no relationship
      between sea ice conditions and adult strandings. Our analysis revealed that male
      seals stranded more frequently than females during the study period and that this
      relationship was strongest during light ice years. In contrast, we found no
      significant difference in mean d (2) between stranded and by-caught harp seals.
      The results demonstrate that sea ice cover and demographic factors have a greater
      influence on harp seal stranding rates than genetic diversity, with only a little
      of the variance in mean d (2) among stranded seals explained by ice cover. Any
      changes in these factors could have major implications for harp seals, and these
      findings should be considered in the development of future management plans for
      the Arctic that incorporate climate variability. 

PMID- 23874760
TI  - RDW to platelet ratio: a novel noninvasive index for predicting hepatic fibrosis
      and cirrhosis in chronic hepatitis B.
AB  - OBJECTIVE: To develop a simple predictive model for significant fibrosis and
      cirrhosis in chronic hepatitis B (CHB) using the routine hematological parameters
      of a complete blood count. METHODS: A total of 458 eligible CHB patients who had
      undergone a liver biopsy were randomly divided into two cohorts: an estimation
      group (n = 310) and a validation group (n = 148). Liver histology was assessed
      according to the Metavir scoring scheme. All common demographics, hematological
      parameters, HBeAg status, HBV DNA, and liver biochemistry were analyzed. RESULTS:
      Based on routinely available clinical parameters (age, sex, HBeAg status, HBV
      DNA, common hematological parameters of a complete blood cell count), a model for
      predicting significant fibrosis (Metavir score >=2) in the estimation group was
      derived using platelets and red cell distribution width (RDW), and another model
      for predicting cirrhosis (Metavir score = 4) was derived using platelets, RDW and
      hemoglobin. A novel index, the RDW to platelet ratio (RPR), was developed to
      amplify the opposing effects of liver fibrosis on the RDW and platelets. The AUCs
      of the RPR for predicting significant fibrosis and cirrhosis were 0.825 and
      0.884, respectively, which is superior to the AAR, FIB-4 and APRI in the
      estimation group. Compared with the two derived models, the RPR has a comparable
      predictive power for significant fibrosis and cirrhosis. Using optimized cutoffs
      (0.10 and 0.16), the RPR accurately predicted 63.1% of cases with significant
      fibrosis and 73.7% of cases with cirrhosis and accurately excluded 85.5% of the
      cases with mild fibrosis and 93.0% of the cases with no cirrhosis. CONCLUSION:
      The RPR, a routinely available, inexpensive and easily calculated index, can
      predict significant fibrosis and cirrhosis in CHB patients with relatively high
      accuracy. The application of this index may reduce the need for liver biopsy in
      CHB patients.

PMID- 23874761
TI  - GPR56 functions together with alpha3beta1 integrin in regulating cerebral
      cortical development.
AB  - Loss of function mutations in GPR56, which encodes a G protein-coupled receptor,
      cause a specific human brain malformation called bilateral frontoparietal
      polymicrogyria (BFPP). Studies from BFPP postmortem brain tissue and Gpr56
      knockout mice have previously showed that GPR56 deletion leads to breaches in the
      pial basement membrane (BM) and neuronal ectopias during cerebral cortical
      development. Since alpha3beta1 integrin also plays a role in pial BM assembly and
      maintenance, we evaluated whether it functions together with GPR56 in regulating
      the same developmental process. We reveal that loss of alpha3 integrin enhances
      the cortical phenotype associated with Gpr56 deletion, and that neuronal
      overmigration through a breached pial BM occurs earlier in double knockout than
      in Gpr56 single knockout mice. These observations provide compelling evidence of
      the synergism of GPR56 and alpha3beta1 integrin in regulating the development of
      cerebral cortex. 

PMID- 23874762
TI  - Understanding dry matter and nitrogen accumulation with time-course for high
      yielding wheat production in China.
AB  - Understanding the time-course of dry matter (DM) and nitrogen (N) accumulation in
      terms of yield-trait relationships is essential to simultaneously increase grain
      yield and synchronize N demand and N supply. We collected 413 data points from 11
      field experiments to address patterns of DM and N accumulation with time in
      relation to grain yield and management of winter wheat in China. Detailed growth
      analysis was conducted at the Zadok growth stages (GS) 25 (regreening), GS30
      (stem elongation), GS60 (anthesis), and GS100 (maturity) in all experiments,
      including DM and N accumulation. Grain yield averaged 7.3 Mg ha(-1), ranging from
      2.1 to 11.2 Mg ha(-1). The percent N accumulation was consistent prior to DM
      accumulation, while both DM and N accumulation increased continuously with
      growing time. Both the highest and fastest DM and N accumulations were observed
      from stem elongation to the anthesis stage. Significant correlations between
      grain yield and DM and N accumulation were found at each of the four growth
      stages, although no positive relationship was observed between grain yield and
      harvest index or N harvest index. The yield increase from 7-9 Mg ha(-1) to >9 Mg
      ha(-1) was mainly attributed to increased DM and N accumulation from stem
      elongation to anthesis. Although applying more N fertilizer increased N
      accumulation during this stage, DM accumulation was not improved, indicating that
      N fertilizer management and related agronomic management should be intensified
      synchronously across the wheat growing season to simultaneously achieve high
      yields and match N demand and N supply. 

PMID- 23874763
TI  - Health and economic burden of obesity in Brazil.
AB  - INTRODUCTION: Higher and lower-middle income countries are increasingly affected
      by obesity. Obesity-related diseases are placing a substantial health and
      economic burden on Brazil. Our aim is to measure the future consequences of these
      trends on the associated disease burden and health care costs. METHOD: A
      previously developed micro-simulation model is used to project the extent of
      obesity, obesity-related diseases and associated healthcare costs to 2050. In
      total, thirteen diseases were considered: coronary heart disease, stroke,
      hypertension, diabetes, osteoarthritis, and eight cancers. We simulated three
      hypothetical intervention scenarios: no intervention, 1% and 5% reduction in body
      mass index (BMI). RESULTS: In 2010, nearly 57% of the Brazilian male population
      was overweight or obese (BMI >=25 kg/m(2)), but the model projects rates as high
      as 95% by 2050. A slightly less pessimistic picture is predicted for females,
      increasing from 43% in 2010 to 52% in 2050. Coronary heart disease, stroke,
      hypertension, cancers, osteoarthritis and diabetes prevalence cases are projected
      to at least double by 2050, reaching nearly 34,000 cases of hypertension by 2050
      (per 100,000). 1% and 5% reduction in mean BMI will save over 800 prevalence
      cases and nearly 3,000 cases of hypertension by 2050 respectively (per 100,000).
      The health care costs will double from 2010 ($5.8 billion) in 2050 alone ($10.1
      billion). Over 40 years costs will reach $330 billion. However, with effective
      interventions the costs can be reduced to $302 billion by 1% and to $273 billion
      by 5% reduction in mean BMI across the population. CONCLUSION: Obesity rates are
      rapidly increasing creating a high burden of disease and associated costs.
      However, an effective intervention to decrease obesity by just 1% will
      substantially reduce obesity burden and will have a significant effect on health
      care expenditure.

PMID- 23874764
TI  - Sodium butyrate protects against severe burn-induced remote acute lung injury in
      rats.
AB  - High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives
      proinflammatory responses when released extracellularly. It plays a key role as a
      distal mediator in the development of acute lung injury (ALI). Sodium butyrate,
      an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1
      expression. This study investigates the effect of sodium butyrate on burn-induced
      lung injury. Sprague-Dawley rats were divided into three groups: 1) sham group,
      sham burn treatment; 2) burn group, third-degree burns over 30% total body
      surface area (TBSA) with lactated Ringer's solution for resuscitation; 3) burn
      plus sodium butyrate group, third-degree burns over 30% TBSA with lactated
      Ringer's solution containing sodium butyrate for resuscitation. The burned
      animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was
      assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio.
      Tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 protein concentrations
      in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked
      immunosorbent assay, and HMGB1 expression in the lung was determined by Western
      blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA)
      concentration were measured to reflect neutrophil infiltration and oxidative
      stress in the lung, respectively. As a result, sodium butyrate significantly
      inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and
      improved the pulmonary histologic changes induced by burn trauma. Furthermore,
      sodium butyrate administration decreased the TNF-alpha and IL-8 concentrations in
      BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs
      after severe burn. These results suggest that sodium butyrate attenuates
      inflammatory responses, neutrophil infiltration, and oxidative stress in the
      lungs, and protects against remote ALI induced by severe burn, which is
      associated with inhibiting HMGB1 expression. 

PMID- 23874765
TI  - Assessing associations between socio-economic environment and self-reported
      health in Amsterdam using bespoke environments.
AB  - BACKGROUND: The study of the relationship between residential environment and
      health at micro area level has a long time been hampered by a lack of micro-scale
      data. Nowadays data is registered at a much more detailed scale. In combination
      with Geographic Information System (GIS)-techniques this creates opportunities to
      look at the relationship at different scales, including very local ones. The
      study illustrates the use of a 'bespoke environment' approach to assess the
      relationship between health and socio-economic environment. METHODS: We created
      these environments by buffer-operations and used micro-scale data on 6-digit
      postcode level to describe these individually tailored areas around survey
      respondents in an accurate way. To capture the full extent of area effects we
      maximized variation in socio-economic characteristics between areas. The area
      effect was assessed using logistic regression analysis. RESULTS: Although the
      contribution of the socio-economic environment in the explanation of health was
      not strong it tended to be stronger at a very local level. A positive association
      was observed only when these factors were measured in buffers smaller than 200
      meters. Stronger associations were observed when restricting the analysis to
      socioeconomically homogeneous buffers. Scale effects proved to be highly
      important but potential boundary effects seemed not to play an important role.
      Administrative areas and buffers of comparable sizes came up with comparable area
      effects. CONCLUSIONS: This study shows that socio-economic area effects reveal
      only on a very micro-scale. It underlines the importance of the availability of
      micro-scale data. Through scaling, bespoke environments add a new dimension to
      study environment and health.

PMID- 23874766
TI  - Altered oscillation and synchronization of default-mode network activity in mild
      Alzheimer's disease compared to mild cognitive impairment: an
      electrophysiological study.
AB  - Some researchers have suggested that the default mode network (DMN) plays an
      important role in the pathological mechanisms of Alzheimer's disease (AD). To
      examine whether the cortical activities in DMN regions show significant
      difference between mild AD from mild cognitive impairment (MCI),
      electrophysiological responses were analyzed from 21 mild Alzheimer's disease
      (AD) and 21 mild cognitive impairment (MCI) patients during an eyes closed,
      resting-state condition. The spectral power and functional connectivity of the
      DMN were estimated using a minimum norm estimate (MNE) combined with fast Fourier
      transform and imaginary coherence analysis. Our results indicated that source
      based EEG maps of resting-state activity showed alterations of cortical spectral
      power in mild AD when compared to MCI. These alterations are characteristic of
      attenuated alpha or beta activities in the DMN, as are enhanced delta or theta
      activities in the medial temporal, inferior parietal, posterior cingulate cortex
      and precuneus. With regard to altered synchronization in AD, altered functional
      interconnections were observed as specific connectivity patterns of connection
      hubs in the precuneus, posterior cingulate cortex, anterior cingulate cortex and
      medial temporal regions. Moreover, posterior theta and alpha power and altered
      connectivity in the medial temporal lobe correlated significantly with scores
      obtained on the Mini-Mental State Examination (MMSE). In conclusion, EEG is a
      useful tool for investigating the DMN in the brain and differentiating early
      stage AD and MCI patients. This is a promising finding; however, further large
      scale studies are needed. 

PMID- 23874767
TI  - Meeting rural demand: a case for combining community-based distribution and
      social marketing of injectable contraceptives in Tigray, Ethiopia.
AB  - BACKGROUND: In Sub-Saharan Africa, policy changes have begun to pave the way for
      community distribution of injectable contraceptives but sustaining such efforts
      remains challenging. Combining social marketing with community-based distribution
      provides an opportunity to recover some program costs and compensate workers with
      proceeds from contraceptive sales. This paper proposes a model for increasing
      access to injectable contraceptives in rural settings by using community-based
      distributers as social marketing agents and incorporating financing systems to
      improve sustainability. METHODS: This intervention was implemented in three
      districts of the Central Zone of Tigray, Ethiopia and program data has been
      collected from November 2011 through October 2012. A total of 137 Community Based
      Reproductive Health Agents (CBRHAs) were trained to provide injectable
      contraceptives and were provided with a loan of 25 injectable contraceptives from
      a drug revolving fund, created with project funds. The price of a single dose
      credited to a CBRHA was 3 birr ($0.17) and they provide injections to women for 5
      birr ($0.29), determined with willingness-to-pay data. Social marketing was used
      to create awareness and generate demand. Both quantitative and qualitative
      methods were used to examine important feasibility aspects of the intervention.
      RESULTS: Forty-four percent of CBRHAs were providing family planning methods at
      the time of the training and 96% believed providing injectable contraceptives
      would improve their services. By October 2012, 137 CBRHAs had successfully
      completed training and provided 2541 injections. Of total injections, 47% were
      provided to new users of injectable contraceptives. Approximately 31% of
      injections were given for free to the poorest women, including adolescents.
      CONCLUSIONS: Insights gained from the first year of implementation of the model
      provide a framework for further expansion in Tigray, Ethiopia. Our experience
      highlights how program planners can tailor interventions to match family planning
      preferences and create more sustainable contraceptive service provision with
      greater impact.

PMID- 23874768
TI  - Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human
      enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and
      drug-induced hemolysis and neonatal jaundice. Our goals were to determine the
      prevalence of G6PD deficiency among Nigerian children of different ethnic
      backgrounds and to identify predictors of G6PD deficiency by analyzing vital
      signs and hematocrit and by asking screening questions about symptoms of
      hemolysis. We studied 1,122 children (561 males and 561 females) aged 1 month to
      15 years. The mean age was 7.4 +/- 3.2 years. Children of Yoruba ethnicity made
      up the largest group (77.5%) followed by those Igbo descent (10.6%) and those of
      Igede (10.2%) and Tiv (1.8%) ethnicity. G6PD status was determined using the
      fluorescent spot method. We found that the overall prevalence of G6PD deficiency
      was 15.3% (24.1% in males, 6.6% in females). Yoruba children had a higher
      prevalence (16.9%) than Igede (10.5%), Igbo (10.1%) and Tiv (5.0%) children. The
      odds of G6PD deficiency were 0.38 times as high in Igbo children compared to
      Yoruba children (p=0.0500). The odds for Igede and Tiv children were not
      significantly different from Yoruba children (p=0.7528 and 0.9789 respectively).
      Mean oxygen saturation, heart rate and hematocrit were not significantly
      different in G6PD deficient and G6PD sufficient children. The odds of being G6PD
      deficient were 2.1 times higher in children with scleral icterus than those
      without (p=0.0351). In conclusion, we determined the prevalence of G6PD
      deficiency in Nigerian sub-populations. The odds of G6PD deficiency were
      decreased in Igbo children compared to Yoruba children. There was no association
      between vital parameters or hematocrit and G6PD deficiency. We found that a
      history of scleral icterus may increase the odds of G6PD deficiency, but we did
      not exclude other common causes of icterus such as sickle cell disease or
      malarial infection.

PMID- 23874769
TI  - An apolipoprotein A-I mimetic peptide designed with a reductionist approach
      stimulates reverse cholesterol transport and reduces atherosclerosis in mice.
AB  - Apolipoprotein A-I (apoA-I) mimetic peptides are considered a promising novel
      therapeutic approach to prevent and/or treat atherosclerosis. An apoA-I mimetic
      peptide ELK-2A2K2E was designed with a reductionist approach and has shown
      exceptional activity in supporting cholesterol efflux but modest anti
      inflammatory and anti-oxidant properties in vitro. In this study we compared
      these in vitro properties with the capacity of this peptide to modify rates of
      reverse cholesterol transport and development of atherosclerosis in mouse models.
      The peptide enhanced the rate of reverse cholesterol transport in C57BL/6 mice
      and reduced atherosclerosis in Apoe(-/-) mice receiving a high fat diet. The
      peptide modestly reduced the size of the plaques in aortic arch, but was highly
      active in reducing vascular inflammation and oxidation. Administration of the
      peptide to Apoe(-/-) mice on a high fat diet reduced the levels of total, high
      density lipoprotein and non-high density lipoprotein cholesterol and
      triglycerides. It increased the proportion of smaller HDL particles in plasma at
      the expense of larger HDL particles, and increased the capacity of the plasma to
      support cholesterol efflux. Thus, ELK-2A2K2E peptide reduced atherosclerosis in
      Apoe(-/-) mice, however, the functional activity profile after chronic in vivo
      administration was different from that found in acute in vitro studies. 

PMID- 23874770
TI  - The serine/threonine phosphatase PP4 is required for pro-B cell development
      through its promotion of immunoglobulin VDJ recombination.
AB  - PP4 phosphatase regulates a number of crucial processes but the role of PP4 in B
      cells has never been reported. We generated B cell-specific pp4 knockout mice and
      have identified an essential role for PP4 in B cell development. Deficiency of
      PP4 in B lineage cells leads to a strong reduction in pre-B cell numbers, an
      absence in immature B cells, and a complete loss of mature B cells. In PP4
      deficient pro-B cells, immunoglobulin (Ig) DJ(H) recombination is impaired and Ig
      u heavy chain expression is greatly decreased. In addition, PP4-deficient pro-B
      cells show an increase of DNA double-strand breaks at Ig loci. Consistent with
      their reduced numbers, residual PP4-deficient pre-B cells accumulate in the G1
      phase, exhibit excessive DNA damage, and undergo increased apoptosis.
      Overexpression of transgenic Ig in PP4-deficient mice rescues the defect in B
      cell development such that the animals have normal numbers of IgM(+) B cells. Our
      study therefore reveals a novel function for PP4 in pro-B cell development
      through its promotion of V(H)DJ(H) recombination.

PMID- 23874771
TI  - The cellular immune mechanism after transfer of chemically extracted acellular
      nerve xenografts.
AB  - Severe peripheral nerve defect by injuries causing functional loss require nerve
      grafting. Autograft has limitations for clinical use because it results in the
      creation of a new nerve injury and the generation of donor site morbidity. Based
      on these limitations, nerve allografts and xenografts provide a readily
      accessible alternative strategy. The aim of the present study was to observe the
      immune mechanism underlying the rejection of chemically extracted acellular nerve
      xenografts, and further evaluate immunogenicity of chemically treated acellular
      nerve grafts for clinical applications. A total of 160 BALB/c mice were randomly
      divided into a negative contrast group (NC, 40 mice), a fresh autograft group
      (AG, 40 mice), a fresh xenogeneic nerve group (FXN, 40 mice) and a chemically
      extracted acellular xenogeneic nerve group (CEXN, 40 mice). Various types of
      nerve grafts were implanted into the thigh muscle of BALB/C mice in the
      corresponding groups. At 3, 7, 14 and 28 days post-operation, the mice (10 mice
      from each group) were sacrificed and their spleens were extracted. The spleens
      were ground into paste. The erythrocytes and other cells were lysed using
      distilled water and the T lymphocytes were collected. Fluorescein isothiocyanate
      (FITC) -labeled monoclonal antibodies (CD3, CD4, CD8, CD25, IL-2, IFN-gamma and
      TNF-alpha) were then added to the solution. The Fluorescence Activated Cell
      Sorting (FACS) was used to determine the positivity rate of the cells combined
      with the monoclonal antibodies above. No significant statistical differences were
      observed between the CEXN, NC and AG groups, so that no obvious immune rejections
      were observed among the chemically extracted acellular nerve xenografts. 

PMID- 23874772
TI  - Increased risk for congenital heart defects in children carrying the ABCB1 Gene
      C3435T polymorphism and maternal periconceptional toxicants exposure.
AB  - BACKGROUNDS: The etiology of congenital heart defect (CHD) is commonly believed
      to involve the interaction of multiple environmental and genetic factors. This
      study aimed to explore the joint effects of the ABCB1 gene C3435T polymorphism
      and maternal periconceptional toxicants exposure on the CHD risk in a Han Chinese
      population. METHODS: An age and gender matched case-control study with
      standardized data collection involving 201 pairs was conducted. Periconceptional
      toxicants exposure was obtained through a structured questionnaire. A job
      exposure matrix (JEM) was used for toxicants exposure assessment. Genotyping of
      the ABCB1 C3435T polymorphism was performed by sequencing. Logistic regression
      analysis was performed to assess the joint effects of the ABCB1 gene C3435T
      polymorphism and toxicants exposure on the risk of CHD. Placenta tissues and
      umbilical cords were collected to investigate the impact of C3435T polymorphism
      on the transcription and translation activities of ABCB1 gene. RESULTS: MATERNAL
      PERICONCEPTIONAL EXPOSURES TO PHTHALATES (ADJUSTED OR: 1.6; 95%CI: 1.0-2.6) and
      alkylphenolic compounds (adjusted OR:1.8; 95%CI:1.1-3.0) were associated with a
      higher incidence of CHDs in general. More cases were carriers of the ABCB1 CC/CT
      genotypes (OR: 2.0, 95%CI: 1.1-3.5, P-value: 0.021). Children carrying the CC/CT
      genotype and periconceptionally exposed to phthalates and alkylphenolic compounds
      suffered almost 3.5-fold increased risk of having CHD than non-exposed children
      with TT genotype (adjusted OR: 3.5, 95%CI: 1.5-7.9, P-value: 0.003), and the OR
      changed to 4.4 for septal defects (adjusted OR: 4.4,95%CI:1.8-10.9,P
      value:0.001). The ABCB1 mRNA expression of the TT genotype was significantly
      higher than that of the CC genotype (P = 0.03). Compared with TT genotype, lower
      P-glycoprotein expression was observed for the CC/CT genotypes. CONCLUSION: The
      C3435T polymorphism in the ABCB1 gene of fetus increases the risks of CHD in a
      Han Chinese population when the mothers are exposed to phthalates and
      alkylphenolic compounds during the periconceptional period, particularly for
      septal defects.

PMID- 23874773
TI  - Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly
      metastatic human breast cancer cells: inhibition of NFkappaB signaling and
      reduction of nitric oxide production.
AB  - BACKGROUND: We have recently reported that Origanummajorana exhibits anticancer
      activity by promoting cell cycle arrest and apoptosis of the metastatic MDA-MB
      231 breast cancer cell line. Here, we extended our study by investigating the
      effect of O. majorana on the migration, invasion and tumor growth of these cells.
      RESULTS: We demonstrate that non-cytotoxic concentrations of O. majorana
      significantly inhibited the migration and invasion of the MDA-MB-231 cells as
      shown by wound-healing and matrigel invasion assays. We also show that O.
      majorana induce homotypic aggregation of MDA-MB-231 associated with an
      upregulation of E-cadherin protein and promoter activity. Furthermore, we show
      that O. majorana decrease the adhesion of MDA-MB-231 to HUVECs and inhibits
      transendothelial migration of MDA-MB-231 through TNF-alpha-activated HUVECs.
      Gelatin zymography assay shows that O. majorana suppresses the activities of
      matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9). ELISA, RT-PCR and Western
      blot results revealed that O. majorana decreases the expression of MMP-2, MMP-9,
      urokinase plasminogen activator receptor (uPAR), ICAM-1 and VEGF. Further
      investigation revealed that O. majorana suppresses the phosphorylation of
      IkappaB, downregulates the nuclear level of NFkappaB and reduces Nitric Oxide
      (NO) production in MDA-MB-231 cells. Most importantly, by using chick embryo
      tumor growth assay, we also show that O. majorana promotes inhibition of tumor
      growth and metastasis in vivo. CONCLUSION: Our findings identify Origanummajorana
      as a promising chemopreventive and therapeutic candidate that modulate breast
      cancer growth and metastasis.

PMID- 23874776
TI  - Load index metrics for an optimized management of web services: a systematic
      evaluation.
AB  - The lack of precision to predict service performance through load indices may
      lead to wrong decisions regarding the use of web services, compromising service
      performance and raising platform cost unnecessarily. This paper presents
      experimental studies to qualify the behaviour of load indices in the web service
      context. The experiments consider three services that generate controlled and
      significant server demands, four levels of workload for each service and six
      distinct execution scenarios. The evaluation considers three relevant
      perspectives: the capability for representing recent workloads, the capability
      for predicting near-future performance and finally stability. Eight different
      load indices were analysed, including the JMX Average Time index (proposed in
      this paper) specifically designed to address the limitations of the other
      indices. A systematic approach is applied to evaluate the different load indices,
      considering a multiple linear regression model based on the stepwise-AIC method.
      The results show that the load indices studied represent the workload to some
      extent; however, in contrast to expectations, most of them do not exhibit a
      coherent correlation with service performance and this can result in stability
      problems. The JMX Average Time index is an exception, showing a stable behaviour
      which is tightly-coupled to the service runtime for all executions. Load indices
      are used to predict the service runtime and therefore their inappropriate use can
      lead to decisions that will impact negatively on both service performance and
      execution cost. 

PMID- 23874775
TI  - Transcription factor Ets1 cooperates with estrogen receptor alpha to stimulate
      estradiol-dependent growth in breast cancer cells and tumors.
AB  - The purpose of this study was to explore the role of transcription factor Ets1 in
      estrogen receptor alpha (ERalpha)-positive breast cancer progression. We
      expressed human Ets1 or empty vector in four human ERalpha-positive breast cancer
      cell lines and observed increased colony formation. Further examination of
      cellular responses in stable Ets1-expressing MCF7 clones displayed increased
      proliferation, migration, and invasion. Ets1-expressing MCF7 tumors grown in the
      mammary fat pads of nude mice exhibited increased rates of tumor growth (7.36+/
      2.47 mm(3)/day) compared to control MCF7 tumors (2.52+/-1.70 mm(3)/day), but
      maintained their dependence on estradiol for tumor growth. Proliferation marker
      Ki-67 staining was not different between control and Ets1-expressing tumors, but
      Ets1-expressing tumors exhibited large necrotic centers and elevated apoptotic
      staining. Ets1 was shown to cooperate with ERalpha and the p160 nuclear receptor
      coactivator (NCOA/SRC) family to increase activation of a consensus estrogen
      response element luciferase reporter construct. Ets1-expressing MCF7 cells also
      exhibited elevated expression of the ERalpha target genes, progesterone receptor
      and trefoil factor 1. Using GST-pulldown assays, Ets1 formed stable complexes
      containing both ERalpha and p160 nuclear receptor coactivators. Taken together,
      these data suggest that the Ets1-dependent estradiol sensitization of breast
      cancer cells and tumors may be partially due to the ability of Ets1 to cooperate
      with ERalpha and nuclear receptor coactivators to stimulate transcriptional
      activity of estrogen-dependent genes. 

PMID- 23874774
TI  - Contribution of individual Ebp Pilus subunits of Enterococcus faecalis OG1RF to
      pilus biogenesis, biofilm formation and urinary tract infection.
AB  - The endocarditis and biofilm-associated pilus (Ebp) operon is a component of the
      core genome of Enterococcus faecalis that has been shown to be important for
      biofilm formation, adherence to host fibrinogen, collagen and platelets, and in
      experimental endocarditis and urinary tract infection models. Here, we created
      single and double deletion mutants of the pilus subunits and sortases; next, by
      combining western blotting, immunoelectron microscopy, and using ebpR in trans to
      increase pilus production, we identified EbpA as the tip pilin and EbpB as anchor
      at the pilus base, the latter attached to cell wall by the housekeeping sortase,
      SrtA. We also confirmed EbpC and Bps as the major pilin and pilin-specific
      sortase, respectively, both required for pilus polymerization. Interestingly,
      pilus length was increased and the number of pili decreased by deleting ebpA,
      while control overexpression of ebpA in trans restored wild-type levels,
      suggesting a dual role for EbpA in both initiation and termination of pilus
      polymerization. We next investigated the contribution of each pilin subunit to
      biofilm formation and UTI. Significant reduction in biofilm formation was
      observed with deletion of ebpA or ebpC (P<0.001) while ebpB was found to be
      dispensable; a similar result was seen in kidney CFUs in experimental UTI
      (DeltaebpA, DeltaebpC, P<=0.0093; DeltaebpB, non-significant, each vs. OG1RF).
      Hence, our data provide important structural and functional information about
      these ubiquitous E. faecalis pili and, based on their demonstrated importance in
      biofilm and infection, suggest EbpA and EbpC as potential targets for antibody
      based therapeutic approaches. 

PMID- 23874777
TI  - The impact of prolonged storage of red blood cells on cancer survival.
AB  - BACKGROUND: The duration of storage of transfused red blood cells (RBC) has been
      associated with poor clinical outcomes in some studies. We sought to establish
      whether prolonged storage of transfused RBC in cancer patients influences overall
      survival (OS) or cancer recurrence. METHODS AND FINDINGS: Patients diagnosed with
      cancer at The Ottawa Regional Cancer Centre between January 01, 2000 and December
      31, 2005 were included (n = 27,591) where 1,929 (7.0%) received RBC transfusions
      within one year from diagnosis. Transfused RBC units were categorized as "new" if
      stored for less than 14 days, "intermediate" if stored between 14 and 28 days and
      "old" if stored for more than 28 days. Baseline characteristics between the
      comparative groups were compared by ANOVA test. Categorical variables and
      continuous variables were compared using Chi-squared and Wilcoxan rank-sum tests
      respectively. Overall survival was not associated with duration of storage of
      transfused RBC with a median survival of 1.2, 1.7, 1.1 years for only new,
      intermediate and old RBC units respectively (p = 0.36). Cancer recurrence was
      significantly higher in patients who received a RBC transfusion than those who
      did not (56.3% vs 33.0% respectively; p<0.0001) but was not affected by the
      duration of storage of transfused RBC (p = 0.06). In multivariate analysis, lung
      cancer, advanced stage, chemotherapy, radiation, cancer-related surgery and
      cancer recurrence were associated with inferior OS (p<0.05), while age, advanced
      stage, lung cancer, and more than 6 units of blood transfused were associated
      with cancer recurrence (p<0.05). The duration of storage of RBC before
      transfusion was not associated with OS or cancer recurrence in multivariate
      analysis. CONCLUSION: In patients diagnosed with cancer, the duration of storage
      of transfused RBC had no impact on OS or cancer recurrence. This suggests that
      our current RBC storage policy of providing RBC of variable duration of storage
      for patients with malignancy is safe.

PMID- 23874779
TI  - How can model comparison help improving species distribution models?
AB  - Today, more than ever, robust projections of potential species range shifts are
      needed to anticipate and mitigate the impacts of climate change on biodiversity
      and ecosystem services. Such projections are so far provided almost exclusively
      by correlative species distribution models (correlative SDMs). However, concerns
      regarding the reliability of their predictive power are growing and several
      authors call for the development of process-based SDMs. Still, each of these
      methods presents strengths and weakness which have to be estimated if they are to
      be reliably used by decision makers. In this study we compare projections of
      three different SDMs (STASH, LPJ and PHENOFIT) that lie in the continuum between
      correlative models and process-based models for the current distribution of three
      major European tree species, Fagussylvatica L., Quercusrobur L. and
      Pinussylvestris L. We compare the consistency of the model simulations using an
      innovative comparison map profile method, integrating local and multi-scale
      comparisons. The three models simulate relatively accurately the current
      distribution of the three species. The process-based model performs almost as
      well as the correlative model, although parameters of the former are not fitted
      to the observed species distributions. According to our simulations, species
      range limits are triggered, at the European scale, by establishment and survival
      through processes primarily related to phenology and resistance to abiotic stress
      rather than to growth efficiency. The accuracy of projections of the hybrid and
      process-based model could however be improved by integrating a more realistic
      representation of the species resistance to water stress for instance, advocating
      for pursuing efforts to understand and formulate explicitly the impact of
      climatic conditions and variations on these processes. 

PMID- 23874778
TI  - The rationale for consuming cognitive enhancement drugs in university students
      and teachers.
AB  - Cognitive enhancement (CE) is the pharmaceutical augmentation of mental abilities
      (e.g., learning or memory) without medical necessity. This topic has recently
      attracted widespread attention in scientific and social circles. However,
      knowledge regarding the mechanisms that underlie the decision to use CE
      medication is limited. To analyze these decisions, we used data from two online
      surveys of randomly sampled university teachers (N = 1,406) and students (N =
      3,486). Each respondent evaluated one randomly selected vignette with regard to a
      hypothetical CE drug. We experimentally varied the characteristics of the drugs
      among vignettes and distributed them among respondents. In addition, the
      respondent's internalization of social norms with respect to CE drug use was
      measured. Our results revealed that students were more willing to enhance
      cognitive performance via drugs than university teachers, although the overall
      willingness was low. The probability of side effects and their strength reduced
      the willingness to use CE drugs among students and university teachers, whereas
      higher likelihoods and magnitudes of CE increased this propensity. In addition,
      the internalized norm against CE drug use influenced decision making: Higher
      internalization decreased the willingness to use such medications. Students'
      internalized norms more strongly affected CE abstinence compared with those of
      university teachers. Furthermore, internalized norms negatively interacted with
      the instrumental incentives for taking CE medication. This internalization
      limited the influence of and deliberation on instrumental incentives. This study
      is the first to provide empirical evidence regarding the importance of social
      norms and their influence on rational decision making with regard to CE. We
      identified previously undiscovered decision-making patterns concerning CE. Thus,
      this study provides insight into the motivators and inhibitors of CE drug use.
      These findings have implications for contending with CE behavior by highlighting
      the magnitude of potential side effects and by informing the debate regarding the
      ethics of CE use. 

PMID- 23874780
TI  - The epidemiology of HIV and HSV-2 infections among women participating in
      microbicide and vaccine feasibility studies in Northern Tanzania.
AB  - OBJECTIVES: To prepare for future HIV prevention trials, we conducted prospective
      cohort studies among women working in food and recreational facilities in
      northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and
      associated risk factors. METHODS: Women aged 18-44 years working in food and
      recreational facilities were screened to determine their eligibility for the
      studies. Between 2008-2010, HIV-negative women were enrolled and followed for 12
      months. At enrolment and 3-monthly, we collected socio-demographic and
      behavioural data, and performed clinical examinations for collection of
      biological specimens that were tested for reproductive tract infections. Risk
      factors for HIV and HSV-2 incidence were investigated using Poisson regression
      models. RESULTS: We screened 2,229 and enrolled 1,378 women. The median age was
      27 years (interquartile range, IQR 22, 33), and median duration working at
      current facility was 2 years. The prevalences of HIV at screening and HSV-2 at
      enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was
      86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI:
      2.8,5.1) and 28.6 (95% CI: 23.5,35.0)/100 person-years, respectively. Women who
      were separated, divorced, or widowed were at increased risk of HIV (adjusted
      incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2) and HSV-2 (aRR = 2.00; 95%
      CI: 1.15,3.47) compared with married women. Women reporting >=3 partners in the
      past 3 months were at higher HIV risk compared with women with 0-1 partner (aRR =
      4.75; 95% CI: 2.10,10.8), while those who had reached secondary education or
      above were at lower risk of HSV-2 compared with women with incomplete primary
      education (aRR = 0.42; 95% CI: 0.22,0.82). CONCLUSIONS: HIV and HSV-2 rates
      remain substantially higher in this cohort than in the general population,
      indicating urgent need for effective interventions. These studies demonstrate the
      feasibility of conducting trials to test new interventions in this highly-mobile
      population.

PMID- 23874781
TI  - Venous thromboembolism in an industrial north american city: temporal
      distribution and association with particulate matter air pollution.
AB  - BACKGROUND: Emerging evidence, mainly from Europe and Asia, indicates that venous
      thromboembolism (VTE) occurs most often in winter. Factors implicated in such
      seasonality are low temperature-mediated exacerbation of coagulation and high
      levels of particulate matter (PM) air pollution. However, in contrast to most
      European and Asian cities, particulate matter pollution peaks in the summer in
      many North American cities. OBJECTIVES: We aimed to exploit this geographical
      difference and examine the temporal distribution of VTE in a cold-weather, North
      American city, Detroit, with a summer PM peak. Our goal was thereby to resolve
      the influence of temperature and PM levels on VTE. METHODS: Our retrospective,
      analytical semi-ecological study used chart review to confirm 1,907 acute,
      ambulatory VTE cases, divided them by location (Detroit versus suburban), and
      plotted monthly VTE frequency distributions. We used Environmental Protection
      Agency data to determine the temporal distribution of PM pollution components in
      Detroit. Suburban PM air pollution is presumed negligible and therefore not
      monitored. RESULTS: Acute VTE cases in Detroit (1,490) exhibited a summer peak
      (June 24(th)) and differed from both a uniform distribution (P<0.01) and also
      that of 1,123 no-VTE cases (P<0.02). Levels of 10 um diameter PM and coarse
      particle (2.5 to 10 um) PM also exhibited summer peaks versus a winter peak for
      2.5 um diameter PM. Contrary to their urban counterparts, suburban cases of acute
      VTE (417) showed no monthly variation. CONCLUSIONS: The summer peak of acute VTE
      in Detroit indicates that low temperature is not a major factor in VTE
      pathogenesis. In contrast, concordance of the 10 um diameter PM, coarse particle,
      and the Detroit VTE monthly distributions, combined with no monthly suburban VTE
      variation, is consistent with a role for PM pollution. Furthermore, divergence of
      the VTE and 2.5 um PM distributions suggests that particle size may play a role.

PMID- 23874782
TI  - Characterization of fructose-1,6-bisphosphate aldolase during anoxia in the
      tolerant turtle, Trachemys scripta elegans: an assessment of enzyme activity,
      expression and structure.
AB  - One of the most adaptive facultative anaerobes among vertebrates is the
      freshwater turtle, Trachemys scripta elegans. Upon a decrease in oxygen supply
      and oxidative phosphorylation, these turtles are able to reduce their metabolic
      rate and recruit anaerobic glycolysis to meet newly established ATP demands.
      Within the glycolytic pathway, aldolase enzymes cleave fructose-1,6-bisphosphate
      to triose phosphates facilitating an increase in anaerobic production of ATP.
      Importantly, this enzyme exists primarily as tissue-specific homotetramers of
      aldolase A, B or C located in skeletal muscle, liver and brain tissue,
      respectively. The present study characterizes aldolase activity and structure in
      the liver tissue of a turtle whose survival greatly depends on increased
      glycolytic output during anoxia. Immunoblot and mass spectrometry analysis
      verified the presence of both aldolase A and B in turtle liver tissue, and
      results from co-immunoprecipitation experiments suggested that in the turtle
      aldolase proteins may exist as an uncommon heterotetramer. Expression levels of
      aldolase A protein increased significantly in liver tissue to 1.59+/-0.11-fold
      after 20 h anoxia, when compared to normoxic control values (P<0.05). A similar
      increase was seen for aldolase B expression. The overall kinetic properties of
      aldolase, when using fructose-1,6-bisphosphate as substrate, were similar to that
      of a previously studied aldolase A and aldolase B heterotetramer, with a Km of
      240 and 180 nM (for normoxic and anoxic turtle liver, respectively). Ligand
      docking of fructose-1,6-bisphosphate to the active site of aldolase A and B
      demonstrated minor differences in both protein:ligand interactions compared to
      rabbit models. It is likely that the turtle is unique in its ability to regulate
      a heterotetramer of aldolase A and B, with a higher overall enzymatic activity,
      to achieve greater rates of glycolytic output and support anoxia survival. 

PMID- 23874784
TI  - Quality, rigour and usefulness of free-text comments collected by a large
      population based longitudinal study - ALSWH.
AB  - While it is common practice for health surveys to include an open-ended question
      asking for additional comments, the responses to these questions are often not
      analysed or used by researchers as data. The current project employed an
      automated semantic program to assess the useability and thematic content of the
      responses to an open-ended free response item included in the Australian
      Longitudinal Study on Women's Health (ALSWH) surveys. The study examined the
      comments of three cohorts of women, born between 1973-78, 1946-51, and 1921-26,
      from Survey 1 (in 1996) and Survey 5 (in 2007-2009). Findings revealed important
      differences in the health status of responders compared to non-responders. Across
      all three cohorts, and at both time points, women who commented tended to have
      poorer physical health (except for women aged 82-87) and social functioning,
      experienced more life events, were less likely to be partnered, and (except for
      women aged 18-23 years) more likely to have higher levels of education, than
      women who did not comment. Results for mental health were mixed. The analysis
      revealed differences between cohorts as well as changes over time. The most
      common themes to emerge for the 1973-78 cohort were health, time, pregnant and
      work, for the 1946-51 cohort, the most common themes were health, life, time and
      work, while for the 1921-26 cohort, the most common themes were husband, health
      and family. The concepts and frequency of concepts changed from the first to the
      fifth survey. For women in the 1973-78 cohort, pregnant emerged as a prevalent
      theme, while eating disappeared. Among women in the 1946-51 cohort, cancer,
      operation and medication emerged as prevalent themes, while for women in the 1921
      26 cohort, the concept children disappeared, while family emerged. This analysis
      suggests that free-text comments are a valuable data source, suitable for
      content, thematic and narrative analysis, particularly when collected over time. 

PMID- 23874783
TI  - Distinct pools of non-glycolytic substrates differentiate brain regions and prime
      region-specific responses of mitochondria.
AB  - Many hereditary diseases are characterized by region-specific toxicity, despite
      the fact that disease-linked proteins are generally ubiquitously expressed. The
      underlying basis of the region-specific vulnerability remains enigmatic. Here, we
      evaluate the fundamental features of mitochondrial and glucose metabolism in
      synaptosomes from four brain regions in basal and stressed states. Although the
      brain has an absolute need for glucose in vivo, we find that synaptosomes prefer
      to respire on non-glycolytic substrates, even when glucose is present. Moreover,
      glucose is metabolized differently in each brain region, resulting in region
      specific "signature" pools of non-glycolytic substrates. The use of non
      glycolytic resources increases and dominates during energy crisis, and triggers a
      marked region-specific metabolic response. We envision that disease-linked
      proteins confer stress on all relevant brain cells, but region-specific
      susceptibility stems from metabolism of non-glycolytic substrates, which limits
      how and to what extent neurons respond to the stress. 

PMID- 23874785
TI  - Morphological and molecular characterization of dietary-induced pseudo-albinism
      during post-embryonic development of Solea senegalensis (Kaup, 1858).
AB  - The appearance of the pseudo-albino phenotype was investigated in developing
      Senegalese sole (Solea senegalensis, Kaup 1858) larvae at morphological and
      molecular levels. In order to induce the development of pseudo-albinos,
      Senegalese sole larvae were fed Artemia enriched with high levels of arachidonic
      acid (ARA). The development of their skin pigmentation was compared to that of a
      control group fed Artemia enriched with a reference commercial product. The
      relative amount of skin melanophores, xanthophores and iridophores revealed that
      larval pigmentation developed similarly in both groups. However, results from
      different relative proportions, allocation patterns, shapes and sizes of skin
      chromatophores revealed changes in the pigmentation pattern between ARA and
      control groups from 33 days post hatching onwards. The new populations of
      chromatophores that should appear at post-metamorphosis were not formed in the
      ARA group. Further, spatial patterns of distribution between the already present
      larval xanthophores and melanophores were suggestive of short-range interaction
      that seemed to be implicated in the degradation of these chromatophores, leading
      to the appearance of the pseudo-albino phenotype. The expression profile of
      several key pigmentation-related genes revealed that melanophore development was
      promoted in pseudo-albinos without a sufficient degree of terminal
      differentiation, thus preventing melanogenesis. Present results suggest the
      potential roles of asip1 and slc24a5 genes on the down-regulation of trp1
      expression, leading to defects in melanin production. Moreover, gene expression
      data supports the involvement of pax3, mitf and asip1 genes in the developmental
      disruption of the new post-metamorphic populations of melanophores, xanthophores
      and iridophores. 

PMID- 23874786
TI  - A depressive endophenotype of mild cognitive impairment and Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a devastating public health problem that
      affects over 5.4 million Americans. Depression increases the risk of Mild
      Cognitive Impairment (MCI) and AD. By understanding the influence of depression
      on cognition, the potential exists to identify subgroups of depressed elders at
      greater risk for cognitive decline and AD. The current study sought to: 1)
      clinically identify a sub group of geriatric patients who suffer from depression
      related cognitive impairment; 2) cross validate this depressive endophenotype of
      MCI/AD in an independent cohort. METHODS AND FINDINGS: Data was analyzed from 519
      participants of Project FRONTIER. Depression was assessed with the GDS30 and
      cognition was assessed using the EXIT 25 and RBANS. Five GDS items were used to
      create the Depressive endophenotype of MCI and AD (DepE). DepE was significantly
      negatively related to RBANS index scores of Immediate Memory (B=-2.22, SE=.37,
      p<0.001), visuospatial skills (B=-1.11, SE=0.26, p<0.001), Language (B=-1.03,
      SE=0.21, p<0.001), Attention (B=-2.56, SE=0.49, p<0.001), and Delayed Memory (B=
      1.54, SE = 037, p<0.001), and higher DepE scores were related to poorer executive
      functioning (EXIT25; B=0.65, SE=0.19, p=0.001). DepE scores significantly
      increased risk for MCI diagnosis (odds ratio [OR] = 2.04; 95% CI=1.54-2.69). Data
      from 235 participants in the TARCC (Texas Alzheimer's Research & Care Consortium)
      were analyzed for cross-validation of findings in an independent cohort. The DepE
      was significantly related to poorer scores on all measures, and a significantly
      predicted of cognitive change over 12- and 24-months. CONCLUSION: The current
      findings suggest that a depressive endophenotype of MCI and AD exists and can be
      clinically identified using the GDS-30. Higher scores increased risk for MCI and
      was cross-validated by predicting AD in the TARCC. A key purpose for the search
      for distinct subgroups of individuals at risk for AD and MCI is to identify novel
      treatment and preventative opportunities.

PMID- 23874787
TI  - The fate of threatened coastal dune habitats in Italy under climate change
      scenarios.
AB  - Coastal dunes worldwide harbor threatened habitats characterized by high
      diversity in terms of plant communities. In Italy, recent assessments have
      highlighted the insufficient state of conservation of these habitats as defined
      by the EU Habitats Directive. The effects of predicted climate change could have
      dramatic consequences for coastal environments in the near future. An assessment
      of the efficacy of protection measures under climate change is thus a priority.
      Here, we have developed environmental envelope models for the most widespread
      dune habitats in Italy, following two complementary approaches: an "indirect"
      plant-species-based one and a simple "direct" one. We analyzed how habitats
      distribution will be altered under the effects of two climate change scenarios
      and evaluated if the current Italian network of protected areas will be effective
      in the future after distribution shifts. While modeling dune habitats with the
      "direct" approach was unsatisfactory, "indirect" models had a good predictive
      performance, highlighting the importance of using species' responses to climate
      change for modeling these habitats. The results showed that habitats closer to
      the sea may even increase their geographical distribution in the near future. The
      transition dune habitat is projected to remain stable, although mobile and fixed
      dune habitats are projected to lose most of their actual geographical
      distribution, the latter being more sensitive to climate change effects. Gap
      analysis highlighted that the habitats' distribution is currently adequately
      covered by protected areas, achieving the conservation target. However, according
      to predictions, protection level for mobile and fixed dune habitats is predicted
      to drop drastically under the climate change scenarios which we examined. Our
      results provide useful insights for setting management priorities and better
      addressing conservation efforts to preserve these threatened habitats in future. 

PMID- 23874788
TI  - Gene fusion analysis in the battle against the African endemic sleeping sickness.
AB  - The protozoan Trypanosoma brucei causes African Trypanosomiasis or sleeping
      sickness in humans, which can be lethal if untreated. Most available
      pharmacological treatments for the disease have severe side-effects. The purpose
      of this analysis was to detect novel protein-protein interactions (PPIs), vital
      for the parasite, which could lead to the development of drugs against this
      disease to block the specific interactions. In this work, the Domain Fusion
      Analysis (Rosetta Stone method) was used to identify novel PPIs, by comparing T.
      brucei to 19 organisms covering all major lineages of the tree of life. Overall,
      49 possible protein-protein interactions were detected, and classified based on
      (a) statistical significance (BLAST e-value, domain length etc.), (b) their
      involvement in crucial metabolic pathways, and (c) their evolutionary history,
      particularly focusing on whether a protein pair is split in T. brucei and fused
      in the human host. We also evaluated fusion events including hypothetical
      proteins, and suggest a possible molecular function or involvement in a certain
      biological process. This work has produced valuable results which could be
      further studied through structural biology or other experimental approaches so as
      to validate the protein-protein interactions proposed here. The evolutionary
      analysis of the proteins involved showed that, gene fusion or gene fission events
      can happen in all organisms, while some protein domains are more prone to fusion
      and fission events and present complex evolutionary patterns. 

PMID- 23874789
TI  - Simplified method for predicting a functional class of proteins in transcription
      factor complexes.
AB  - BACKGROUND: Initiation of transcription is essential for most of the cellular
      responses to environmental conditions and for cell and tissue specificity. This
      process is regulated through numerous proteins, their ligands and mutual
      interactions, as well as interactions with DNA. The key such regulatory proteins
      are transcription factors (TFs) and transcription co-factors (TcoFs). TcoFs are
      important since they modulate the transcription initiation process through
      interaction with TFs. In eukaryotes, transcription requires that TFs form
      different protein complexes with various nuclear proteins. To better understand
      transcription regulation, it is important to know the functional class of
      proteins interacting with TFs during transcription initiation. Such information
      is not fully available, since not all proteins that act as TFs or TcoFs are yet
      annotated as such, due to generally partial functional annotation of proteins. In
      this study we have developed a method to predict, using only sequence composition
      of the interacting proteins, the functional class of human TF binding partners to
      be (i) TF, (ii) TcoF, or (iii) other nuclear protein. This allows for
      complementing the annotation of the currently known pool of nuclear proteins.
      Since only the knowledge of protein sequences is required in addition to protein
      interaction, the method should be easily applicable to many species. RESULTS:
      Based on experimentally validated interactions between human TFs with different
      TFs, TcoFs and other nuclear proteins, our two classification systems
      (implemented as a web-based application) achieve high accuracies in
      distinguishing TFs and TcoFs from other nuclear proteins, and TFs from TcoFs
      respectively. CONCLUSION: As demonstrated, given the fact that two proteins are
      capable of forming direct physical interactions and using only information about
      their sequence composition, we have developed a completely new method for
      predicting a functional class of TF interacting protein partners with high
      precision and accuracy.

PMID- 23874790
TI  - Cell survival signalling through PPARdelta and arachidonic acid metabolites in
      neuroblastoma.
AB  - Retinoic acid (RA) has paradoxical effects on cancer cells: promoting cell death,
      differentiation and cell cycle arrest, or cell survival and proliferation.
      Arachidonic acid (AA) release occurs in response to RA treatment and, therefore,
      AA and its downstream metabolites may be involved in cell survival signalling. To
      test this, we inhibited phospholipase A2-mediated AA release, cyclooxygenases and
      lipoxygenases with small-molecule inhibitors to determine if this would sensitise
      cells to cell death after RA treatment. The data suggest that, in response to RA,
      phospholipase A2-mediated release of AA and subsequent metabolism by
      lipoxygenases is important for cell survival. Evidence from gene expression
      reporter assays and PPARdelta knockdown suggests that lipoxygenase metabolites
      activate PPARdelta. The involvement of PPARdelta in cell survival is supported by
      results of experiments with the PPARdelta inhibitor GSK0660 and siRNA-mediated
      knockdown. Quantitative reverse transcriptase PCR studies demonstrated that
      inhibition of 5-lipoxygenase after RA treatment resulted in a strong up
      regulation of mRNA for PPARdelta2, a putative inhibitory PPARdelta isoform. Over
      expression of PPARdelta2 using a tetracycline-inducible system in neuroblastoma
      cells reduced proliferation and induced cell death. These data provide evidence
      linking lipoxygenases and PPARdelta in a cell survival-signalling mechanism and
      suggest new drug-development targets for malignant and hyper-proliferative
      diseases.

PMID- 23874791
TI  - Armed rollers: does nestling's vomit function as a defence against predators?
AB  - Chemical defences against predators are widespread in the animal kingdom although
      have been seldom reported in birds. Here, we investigate the possibility that the
      orange liquid that nestlings of an insectivorous bird, the Eurasian roller
      (Coracias garrulus), expel when scared at their nests acts as a chemical defence
      against predators. We studied the diet of nestling rollers and vomit origin, its
      chemical composition and deterrent effect on a mammal generalist predator. We
      also hypothesized that nestling rollers, as their main prey (i.e. grasshoppers)
      do from plants, could sequester chemicals from their prey for their use.
      Grasshoppers, that also regurgitate when facing to a threat, store the harmful
      substances used by plants to defend themselves against herbivores. We found that
      nestling rollers only vomit after being grasped and moved. The production of
      vomit depended on food consumption and the vomit contained two deterrent
      chemicals (hydroxycinnamic and hydroxybenzoic acids) stored by grasshoppers and
      used by plants to diminish herbivory, suggesting that they originate from the
      rollers' prey. Finally, we showed for the first time that the oral secretion of a
      vertebrate had a deterrent effect on a model predator because vomit of nestling
      rollers made meat distasteful to dogs. These results support the idea that the
      vomit of nestling rollers is a chemical defence against predators. 

PMID- 23874792
TI  - The N276 glycosylation site is required for HIV-1 neutralization by the CD4
      binding site specific HJ16 monoclonal antibody.
AB  - Immunogen design for HIV-1 vaccines could be based on epitope identification of
      naturally occurring neutralizing antibodies in infected patients. A tier 2
      neutralizing monoclonal antibody (mAb), HJ16 recognizes a new epitope in the CD4
      binding site (CD4bs) region that only partially overlaps with the b12 epitope. We
      aimed to identify the critical binding site by resistance induction in a
      sensitive primary CRF02_AG strain. In four independent dose-escalation studies,
      the N276D mutation was consistently the only alteration found and it was
      confirmed to be responsible for resistance to HJ16 by site-directed mutagenesis
      in envelopes (envs) of the homologous CRF02_AG, as well as of a subtype A and a
      subtype C primary isolate. This mutation removes an N-linked glycosylation site.
      The effect of N276D was very selective, as it failed to confer resistance to a
      range of other entry inhibitors. Remarkably, sensitivity to the CD4bs VRC01 and
      VRC03 mAbs was increased in the N276D mutated viruses. These data indicate that
      binding of the CD4bs specific HJ16 mAb critically depends on the interaction with
      the N276-glycan, thus indicating that HJ16 is the first glycan dependent CD4bs
      specific mAb. 

PMID- 23874793
TI  - Natural killer cell cytokine response to M. bovis BCG Is associated with
      inhibited proliferation, increased apoptosis and ultimate depletion of
      NKp44(+)CD56(bright) cells.
AB  - Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed
      as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy
      of cancers and for treatment of parasitic infections. The underlying mechanisms
      are thought to rely on its immunomodulatory properties including the recruitment
      of natural killer (NK) cells. In that context, we aimed to study the impact of M.
      bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production,
      proliferation and cell survival of purified human NK cells following exposure to
      single live particles of mycobacteria. We found that M. bovis BCG mediates
      apoptosis of NK cells only in the context of IL-2 stimulation during which
      CD56(bright) NK cells are releasing IFN-gamma in response to mycobacteria. We
      found that the presence of mycobacteria prevented the IL-2 induced proliferation
      and surface expression of NKp44 receptor by the CD56(bright) population. In
      summary, we observed that M. bovis BCG is modulating the functions of
      CD56(bright) NK cells to drive this subset to produce IFN-gamma before subsequent
      programmed cell death. Therefore, IFN-gamma production by CD56(bright) cells
      constitutes the main effector mechanism of NK cells that would contribute to the
      benefits observed for M. bovis BCG as an immunotherapeutic agent. 

PMID- 23874794
TI  - Mitochondrial acclimation capacities to ocean warming and acidification are
      limited in the antarctic Nototheniid Fish, Notothenia rossii and Lepidonotothen
      squamifrons.
AB  - Antarctic notothenioid fish are characterized by their evolutionary adaptation to
      the cold, thermostable Southern Ocean, which is associated with unique
      physiological adaptations to withstand the cold and reduce energetic requirements
      but also entails limited compensation capacities to environmental change. This
      study compares the capacities of mitochondrial acclimation to ocean warming and
      acidification between the Antarctic nototheniid Notothenia rossii and the sub
      Antarctic Lepidonotothen squamifrons, which share a similar ecology, but
      different habitat temperatures. After acclimation of L. squamifrons to 9 degrees
      C and N. rossii to 7 degrees C (normocapnic/hypercapnic, 0.2 kPa CO2/2000 ppm
      CO2) for 4-6 weeks, we compared the capacities of their mitochondrial respiratory
      complexes I (CI) and II (CII), their P/O ratios (phosphorylation efficiency),
      proton leak capacities and mitochondrial membrane fatty acid compositions. Our
      results reveal reduced CII respiration rates in warm-acclimated L. squamifrons
      and cold hypercapnia-acclimated N. rossii. Generally, L. squamifrons displayed a
      greater ability to increase CI contribution during acute warming and after warm
      acclimation than N. rossii. Membrane unsaturation was not altered by warm or
      hypercapnia-acclimation in both species, but membrane fatty acids of warm
      acclimated L. squamifrons were less saturated than in warm normocapnia
      /hypercapnia-acclimated N. rossii. Proton leak capacities were not affected by
      warm or hypercapnia-acclimation of N. rossii. We conclude that an acclimatory
      response of mitochondrial capacities may include higher thermal plasticity of CI
      supported by enhanced utilization of anaplerotic substrates (via oxidative
      decarboxylation reactions) feeding into the citrate cycle. L. squamifrons
      possesses higher relative CI plasticities than N. rossii, which may facilitate
      the usage of energy efficient NADH-related substrates under conditions of
      elevated energy demand, possibly induced by ocean warming and acidification. The
      observed adjustments of electron transport system complexes with a higher flux
      through CI under warming and acidification suggest a metabolic acclimation
      potential of the sub-Antarctic L. squamifrons, but only limited acclimation
      capacities for N. rossii. 

PMID- 23874795
TI  - The effects of Ca2+ and MgADP on force development during and after muscle length
      changes.
AB  - The goal of this study was to compare the effects of Ca(2+) and MgADP activation
      on force development in skeletal muscles during and after imposed length changes.
      Single fibres dissected from the rabbit psoas were (i) activated in pCa(2+)4.5
      and pCa(2+)6.0, or (ii) activated in pCa(2+)4.5 before and after administration
      of 10 mM MgADP. Fibres were activated in sarcomere lengths (SL) of 2.65 um and
      2.95 um, and subsequently stretched or shortened (5%SL at 1.0 SL.s(-1)) to reach
      a final SL of 2.80 um. The kinetics of force during stretch were not altered by
      pCa(2+) or MgADP, but the fast change in the slope of force development (P1)
      observed during shortening and the corresponding SL extension required to reach
      the change (L1) were higher in pCa(2+)6.0 (P1 = 0.22 +/- 0.02 Po; L1 = 5.26 +/-
      0.24 nm.HS(.1)) than in pCa(2+)4.5 (P1 = 0.15 +/- 0.01 Po; L1 = 4.48 +/- 0.25
      nm.HS(.1)). L1 was also increased by MgADP activation during shortening. Force
      enhancement after stretch was lower in pCa(2+)4.5 (14.9 +/- 5.4%) than in
      pCa(2+)6.0 (38.8 +/- 7.5%), while force depression after shortening was similar
      in both Ca(2+) concentrations. The stiffness accompanied the force behavior after
      length changes in all situations. MgADP did not affect the force behavior after
      length changes, and stiffness did not accompany the changes in force development
      after stretch. Altogether, these results suggest that the mechanisms of force
      generation during and after stretch are different from those obtained during and
      after shortening.

PMID- 23874796
TI  - Independent losses of visual perception genes Gja10 and Rbp3 in echolocating bats
      (Order: Chiroptera).
AB  - A trade-off between the sensory modalities of vision and hearing is likely to
      have occurred in echolocating bats as the sophisticated mechanism of laryngeal
      echolocation requires considerable neural processing and has reduced the reliance
      of echolocating bats on vision for perceiving the environment. If such a trade
      off exists, it is reasonable to hypothesize that some genes involved in visual
      function may have undergone relaxed selection or even functional loss in
      echolocating bats. The Gap junction protein, alpha 10 (Gja10, encoded by Gja10
      gene) is expressed abundantly in mammal retinal horizontal cells and plays an
      important role in horizontal cell coupling. The interphotoreceptor retinoid
      binding protein (Irbp, encoded by the Rbp3 gene) is mainly expressed in
      interphotoreceptor matrix and is known to be critical for normal functioning of
      the visual cycle. We sequenced Gja10 and Rbp3 genes in a taxonomically wide range
      of bats with divergent auditory characteristics (35 and 18 species for Gja10 and
      Rbp3, respectively). Both genes have became pseudogenes in species from the
      families Hipposideridae and Rhinolophidae that emit constant frequency
      echolocation calls with Doppler shift compensation at high-duty-cycles (the most
      sophisticated form of biosonar known), and in some bat species that emit
      echolocation calls at low-duty-cycles. Our study thus provides further evidence
      for the hypothesis that a trade-off occurs at the genetic level between vision
      and echolocation in bats. 

PMID- 23874797
TI  - MyD88-dependent pathways in leukocytes affect the retina in diabetes.
AB  - BACKGROUND: Previous studies by us and other have provided evidence that
      leukocytes play a critical role in the development of diabetic retinopathy,
      suggesting a possible role of the innate immune system in development of the
      retinopathy. Since MyD88 is a convergence point for signaling pathways of the
      innate immune system (including Toll-Like Receptors (TLRs) and interleukin-1beta
      (IL-1beta)), the purpose of this study was to assess the role of MyD88 and its
      dependent pathways on abnormalities that develop in retina and white blood cells
      related to diabetic retinopathy. METHODS: C57BL/6J mice were made diabetic with
      streptozotocin. Chimeric mice were generated in which MyD88-dependent pathways
      were deleted from bone marrow-derived only. Mice were sacrificed at 2 mos of
      diabetes for assessment of, leukostasis, albumin accumulation in neural retina,
      leukocyte-mediated killing of retinal endothelial cells, and cytokine/chemokine
      generation by retinas of diabetic mice in response to TLR agonists. RESULTS: IL-6
      and CXCL1 were generated in retinas from diabetic (but not nondiabetic mice)
      following incubation with Pam3CysK/TLR2, but incubation with other TLR ligands or
      IL-1beta did not induce cytokine production in retinas from nondiabetic or
      diabetic mice. Diabetes-induced abnormalities (leukostasis, ICAM-1 expression on
      the luminal surface of the vascular endothelium, retinal superoxide generation)
      were significantly inhibited by removing either MyD88 or the signaling pathways
      regulated by it (TLRs 2 and 4, and IL-1beta) from bone marrow-derived cells only.
      Leukocyte-mediated killing of endothelial cells tended to be decreased in the
      marrow-derived cells lacking TLR2/4, but the killing was significantly
      exacerbated if the marrow cells lacked MyD88 or the receptor for IL-1beta (IL
      1betar). CONCLUSIONS: MyD88-dependent pathways play an important role in the
      development of diabetes-induced inflammation in the retina, and inhibition of
      MyD88 might be a novel target to inhibit early abnormalities of diabetic
      retinopathy and other complications of diabetes.

PMID- 23874798
TI  - Electrical stimulation of inner retinal neurons in wild-type and retinally
      degenerate (rd/rd) mice.
AB  - Electrical stimulation of the retina following photoreceptor degeneration in
      diseases such as retinitis pigmentosa and age-related macular degeneration has
      become a promising therapeutic strategy for the restoration of vision. Many
      retinal neurons remain functional following photoreceptor degeneration; however,
      the responses of the different classes of cells to electrical stimuli have not
      been fully investigated. Using whole-cell patch clamp electrophysiology in
      retinal slices we investigated the response to electrical stimulation of cells of
      the inner nuclear layer (INL), pre-synaptic to retinal ganglion cells, in wild
      type and retinally degenerate (rd/rd) mice. The responses of these cells to
      electrical stimulation were extremely varied, with both extrinsic and intrinsic
      evoked responses observed. Further examination of the intrinsically evoked
      responses revealed direct activation of both voltage-gated Na(+) channels and
      K(+) channels. The expression of these channels, which is particularly varied
      between INL cells, and the stimulus intensity, appears to dictate the polarity of
      the eventual response. Retinally degenerate animals showed similar responses to
      electrical stimulation of the retina to those of the wild-type, but the relative
      representation of each response type differed. The most striking difference
      between genotypes was the existence of a large amplitude oscillation in the
      majority of INL cells in rd/rd mice (as previously reported) that impacted on the
      signal to noise ratio following electrical stimulation. This confounding
      oscillation may significantly reduce the efficacy of electrical stimulation of
      the degenerate retina, and a greater understanding of its origin will potentially
      enable it to be dampened or eliminated. 

PMID- 23874799
TI  - Tracing the transcriptomic changes in synthetic Trigenomic allohexaploids of
      Brassica using an RNA-Seq approach.
AB  - Polyploidization has played an important role in plant evolution and speciation,
      and newly formed allopolyploids have experienced rapid transcriptomic changes.
      Here, we compared the transcriptomic differences between a synthetic Brassica
      allohexaploid and its parents using a high-throughput RNA-Seq method. A total of
      35,644,409 sequence reads were generated, and 32,642 genes were aligned from the
      data. Totals of 29,260, 29,060, and 29,697 genes were identified in Brassicarapa,
      Brassicacarinata, and Brassica allohexaploid, respectively. We compared 7,397
      differentially expressed genes (DEGs) between Brassica hexaploid and its parents,
      as well as 2,545 nonadditive genes of Brassica hexaploid. We hypothesized that
      the higher ploidy level as well as secondary polyploidy might have influenced
      these changes. The majority of the 3,184 DEGs between Brassica hexaploid and its
      paternal parent, B. rapa, were involved in the biosynthesis of secondary
      metabolites, plant-pathogen interactions, photosynthesis, and circadian rhythm.
      Among the 2,233 DEGs between Brassica hexaploid and its maternal parent, B.
      carinata, several played roles in plant-pathogen interactions, plant hormone
      signal transduction, ribosomes, limonene and pinene degradation, photosynthesis,
      and biosynthesis of secondary metabolites. There were more significant
      differences in gene expression between the allohexaploid and its paternal parent
      than between it and its maternal parent, possibly partly because of cytoplasmic
      and maternal effects. Specific functional categories were enriched among the
      2,545 nonadditive genes of Brassica hexaploid compared with the additive genes;
      the categories included response to stimulus, immune system process, cellular
      process, metabolic process, rhythmic process, and pigmentation. Many
      transcription factor genes, methyltransferases, and methylation genes showed
      differential expression between Brassica hexaploid and its parents. Our results
      demonstrate that the Brassica allohexaploid can generate extensive transcriptomic
      diversity compared with its parents. These changes may contribute to the normal
      growth and reproduction of allohexaploids. 

PMID- 23874800
TI  - Systems biology analysis of Zymomonas mobilis ZM4 ethanol stress responses.
AB  - BACKGROUND: Zymomonas mobilis ZM4 is a capable ethanologenic bacterium with high
      ethanol productivity and ethanol tolerance. Previous studies indicated that
      several stress-related proteins and changes in the ZM4 membrane lipid composition
      may contribute to ethanol tolerance. However, the molecular mechanisms of its
      ethanol stress response have not been elucidated fully. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, ethanol stress responses were investigated using systems
      biology approaches. Medium supplementation with an initial 47 g/L (6% v/v)
      ethanol reduced Z. mobilis ZM4 glucose consumption, growth rate and ethanol
      productivity compared to that of untreated controls. A proteomic analysis of
      early exponential growth identified about one thousand proteins, or approximately
      55% of the predicted ZM4 proteome. Proteins related to metabolism and stress
      response such as chaperones and key regulators were more abundant in the early
      ethanol stress condition. Transcriptomic studies indicated that the response of
      ZM4 to ethanol is dynamic, complex and involves many genes from all the different
      functional categories. Most down-regulated genes were related to translation and
      ribosome biogenesis, while the ethanol-upregulated genes were mostly related to
      cellular processes and metabolism. Transcriptomic data were used to update Z.
      mobilis ZM4 operon models. Furthermore, correlations among the transcriptomic,
      proteomic and metabolic data were examined. Among significantly expressed genes
      or proteins, we observe higher correlation coefficients when fold-change values
      are higher. CONCLUSIONS: Our study has provided insights into the responses of Z.
      mobilis to ethanol stress through an integrated "omics" approach for the first
      time. This systems biology study elucidated key Z. mobilis ZM4 metabolites, genes
      and proteins that form the foundation of its distinctive physiology and its
      multifaceted response to ethanol stress.

PMID- 23874801
TI  - Natural selection and neutral evolution jointly drive population divergence
      between alpine and lowland ecotypes of the allopolyploid plant Anemone multifida
      (Ranunculaceae).
AB  - Population differentiation can be driven in large part by natural selection, but
      selectively neutral evolution can play a prominent role in shaping patters of
      population divergence. The decomposition of the evolutionary history of
      populations into the relative effects of natural selection and selectively
      neutral evolution enables an understanding of the causes of population divergence
      and adaptation. In this study, we examined heterogeneous genomic divergence
      between alpine and lowland ecotypes of the allopolyploid plant, Anemone
      multifida. Using peak height and dominant AFLP data, we quantified population
      differentiation at non-outlier (neutral) and outlier loci to determine the
      potential contribution of natural selection and selectively neutral evolution to
      population divergence. We found 13 candidate loci, corresponding to 2.7% of loci,
      with signatures of divergent natural selection between alpine and lowland
      populations and between alpine populations (Fst  = 0.074-0.445 at outlier loci),
      but neutral population differentiation was also evident between alpine
      populations (FST  = 0.041-0.095 at neutral loci). By examining population
      structure at both neutral and outlier loci, we determined that the combined
      effects of selection and neutral evolution are associated with the divergence of
      alpine populations, which may be linked to extreme abiotic conditions and
      isolation between alpine sites. The presence of outlier levels of genetic
      variation in structured populations underscores the importance of separately
      analyzing neutral and outlier loci to infer the relative role of divergent
      natural selection and neutral evolution in population divergence. 

PMID- 23874802
TI  - Long-term trends in visibility and at Chengdu, China.
AB  - Long-term (1973 to 2010) trends in visibility at Chengdu, China were investigated
      using meteorological data from the U.S. National Climatic Data Center. The visual
      range exhibited a declining trend before 1982, a slight increase between 1983 and
      1995, a sharp decrease between 1996 and 2005, and some improvements after 2006.
      The trends in visibility were generally consistent with the economic development
      and implementation of pollution controls in China. Intensive PM2.5 measurements
      were conducted from 2009 to 2010 to determine the causes of visibility
      degradation. An analysis based on a modification of the IMPROVE approach
      indicated that PM2.5 ammonium bisulfate contributed 27.7% to the light extinction
      coefficient (bext ); this was followed by organic mass (21.7%), moisture (20.6%),
      and ammonium nitrate (16.3%). Contributions from elemental carbon (9.4%) and soil
      dust (4.3%) were relatively minor. Anthropogenic aerosol components (sulfate,
      nitrate, and elemental carbon) and moisture at the surface also were important
      determinants of the aerosol optical depth (AOD) at 550 nm, and the spatial
      distributions of both bext and AOD were strongly affected by regional topography.
      A Positive Matrix Factorization receptor model suggested that coal combustion was
      the largest contributor to PM2.5 mass (42.3%) and the dry-air light-scattering
      coefficient (47.7%); this was followed by vehicular emissions (23.4% and 20.5%,
      respectively), industrial emissions (14.9% and 18.8%), biomass burning (12.8% and
      11.9%), and fugitive dust (6.6% and 1.1%). Our observations provide a scientific
      basis for improving visibility in this area. 

PMID- 23874803
TI  - Identification and expression of the CCAP receptor in the Chagas' disease vector,
      Rhodnius prolixus, and its involvement in cardiac control.
AB  - Rhodnius prolixus is the vector of Chagas' disease, by virtue of transmitting the
      parasite Trypanosoma cruzi. There is no cure for Chagas' disease and therefore
      controlling R. prolixus is currently the only method of prevention. Understanding
      the physiology of the disease vector is an important step in developing control
      measures. Crustacean cardioactive peptide (CCAP) is an important neuropeptide in
      insects because it has multiple physiological roles such as controlling heart
      rate and modulating ecdysis behaviour. In this study, we have cloned the cDNA
      sequence of the CCAP receptor (RhoprCCAPR) from 5(th) instar R. prolixus and
      found it to be a G-protein coupled receptor (GPCR). The spatial expression
      pattern in 5(th) instars reveals that the RhoprCCAPR transcript levels are high
      in the central nervous system, hindgut and female reproductive systems, and lower
      in the salivary glands, male reproductive tissues and a pool of tissues including
      the dorsal vessel, trachea, and fat body. Interestingly, the RhoprCCAPR
      expression is increased prior to ecdysis and decreased post-ecdysis. A functional
      receptor expression assay confirms that the RhoprCCAPR is activated by CCAP (EC50
      = 12 nM) but not by adipokinetic hormone, corazonin or an extended FMRFamide. The
      involvement of CCAP in controlling heartbeat frequency was studied in vivo and in
      vitro by utilizing RNA interference. In vivo, the basal heartbeat frequency is
      decreased by 31% in bugs treated with dsCCAPR. Knocking down the receptor in
      dsCCAPR-treated bugs also resulted in loss of function of applied CCAP in vitro.
      This is the first report of a GPCR knock-down in R. prolixus and the first report
      showing that a reduction in CCAPR transcript levels leads to a reduction in
      cardiac output in any insect. 

PMID- 23874804
TI  - A comparison of measures of boldness and their relationships to survival in young
      fish.
AB  - Boldness is the propensity of an animal to engage in risky behavior. Many
      variations of novel-object or novel-environment tests have been used to quantify
      the boldness of animals, although the relationship between test outcomes has
      rarely been investigated. Furthermore, the relationship of outcomes to any
      ecological aspect of fitness is generally assumed, rather than measured directly.
      Our study is the first to compare how the outcomes of the same test of boldness
      differ among observers and how different tests of boldness relate to the survival
      of individuals in the field. Newly-metamorphosed lemon damselfish, Pomacentrus
      moluccensis, were placed onto replicate patches of natural habitat. Individual
      behavior was quantified using four tests (composed of a total of 12 different
      measures of behavior): latency to enter a novel environment, activity in a novel
      environment, and reactions to threatening and benign novel objects. After
      behavior was quantified, survival was monitored for two days during which time
      fish were exposed to natural predators. Variation among observers was low for
      most of the 12 measures, except distance moved and the threat test (reaction to
      probe thrust), which displayed unacceptable amounts of inter-observer variation.
      Overall, the results of the behavioral tests suggested that novel environment and
      novel object tests quantified similar behaviors, yet these behavioral measures
      were not interchangeable. Multiple measures of behavior within the context of
      novel environment or object tests were the most robust way to assess boldness and
      these measures have a complex relationship with survivorship of young fish in the
      field. Body size and distance ventured from shelter were the only variables that
      had a direct and positive relationship with survival. 

PMID- 23874805
TI  - Identification of serum monocyte chemoattractant protein-1 and prolactin as
      potential tumor markers in hepatocellular carcinoma.
AB  - Early diagnosis of hepatocellullar carcinoma (HCC) remains a challenge. The
      current practice of serum alpha-fetoprotein (AFP) measurement is inadequate. Here
      we utilized a proteomic approach to identify novel serum biomarkers for
      distinguishing HCC patients from non-cancer controls. We profiled the serum
      proteins in a group of 58 resectable HCC patients and 11 non-HCC chronic
      hepatitis B (HBV) carrier samples from the Singapore General Hospital (SGH) using
      the RayBio(r) L-Series 507 Antibody Array and found 113 serum markers that were
      significantly modulated between HCC and control groups. Selected potential
      biomarkers from this list were quantified using a multiplex sandwich enzyme
      linked immunosorbent assay (ELISA) array in an expanded SGH cohort (126
      resectable HCC patients and 115 non-HCC chronic HBV carriers (NC group)),
      confirming that serum prolactin and monocyte chemoattractant protein-1 (MCP-1)
      were significantly upregulated in HCC patients. This finding of serum MCP-1
      elevation in HCC patients was validated in a separate cohort of serum samples
      from the Mochtar Riady Institute for Nanotechnology, Indonesia (98 resectable
      HCC, 101 chronic hepatitis B patients and 100 asymptomatic HBV/HCV carriers) by
      sandwich ELISA. MCP-1 and prolactin levels were found to correlate with AFP,
      while MCP-1 also correlated with disease stage. Subsequent receiver operating
      characteristic (ROC) analysis of AFP, prolactin and MCP-1 in the SGH cohort and
      comparing their area under the ROC curve (AUC) indicated that neither prolactin
      nor MCP-1 on their own performed better than AFP. However, the combination of
      AFP+MCP-1 (AUC, 0.974) had significantly superior discriminative ability than AFP
      alone (AUC, 0.942; p<0.001). In conclusion, prolactin and MCP-1 are overexpressed
      in HCC and are conveniently quantifiable in patients' sera by ELISA. MCP-1
      appears to be a promising complementary biomarker for HCC diagnosis and this MCP
      1+AFP model should be further evaluated as potential biomarker on a larger scale
      in patients at-risk of HCC. 

PMID- 23874807
TI  - Epidemiology of subacute sclerosing panencephalitis (SSPE) in Germany from 2003
      to 2009: a risk estimation.
AB  - Subacute sclerosing panencephalitis (SSPE) is a fatal long-term complication of
      measles infection. We performed an estimation of the total number of SSPE cases
      in Germany for the period 2003 to 2009 and calculated the risk of SSPE after an
      acute measles infection. SSPE cases were collected from the Surveillance Unit for
      Rare Paediatric Diseases in Germany and the Institute of Virology and
      Immunobiology at the University of Wurzburg. The total number of SSPE cases was
      estimated by capture-recapture analysis. For the period 2003 to 2009, 31 children
      with SSPE who were treated at German hospitals were identified. The capture
      recapture estimate was 39 cases (95% confidence interval: 29.2-48.0). The risk of
      developing SSPE for children contracting measles infection below 5 years of age
      was calculated as 1?1700 to 1?3300. This risk is in the same order of magnitude
      as the risk of a fatal acute measles infection. 

PMID- 23874806
TI  - Changes in the transcriptome of the human endometrial Ishikawa cancer cell line
      induced by estrogen, progesterone, tamoxifen, and mifepristone (RU486) as
      detected by RNA-sequencing.
AB  - BACKGROUND: Estrogen (E2) and progesterone (P4) are key players in the maturation
      of the human endometrium. The corresponding steroid hormone modulators, tamoxifen
      (TAM) and mifepristone (RU486) are widely used in breast cancer therapy and for
      contraception purposes, respectively. METHODOLOGY/PRINCIPAL FINDINGS: Gene
      expression profiling of the human endometrial Ishikawa cancer cell line treated
      with E2 and P4 for 3 h and 12 h, and TAM and RU486 for 12 h, was performed using
      RNA-sequencing. High levels of mRNA were detected for genes, including PSAP,
      ATP5G2, ATP5H, and GNB2L1 following E2 or P4 treatment. A total of 82 biomarkers
      for endometrial biology were identified among E2 induced genes, and 93 among P4
      responsive genes. Identified biomarkers included: EZH2, MDK, MUC1, SLIT2, and
      IL6ST, which are genes previously associated with endometrial receptivity.
      Moreover, 98.8% and 98.6% of E2 and P4 responsive genes in Ishikawa cells,
      respectively, were also detected in two human mid-secretory endometrial biopsy
      samples. TAM treatment exhibited both antagonistic and agonistic effects of E2,
      and also regulated a subset of genes independently. The cell cycle regulator
      cyclin D1 (CCND1) showed significant up-regulation following treatment with TAM.
      RU486 did not appear to act as a pure antagonist of P4 and a functional analysis
      of RU486 response identified genes related to adhesion and apoptosis, including
      down-regulated genes associated with cell-cell contacts and adhesion as CTNND1,
      JUP, CDH2, IQGAP1, and COL2A1. CONCLUSIONS: Significant changes in gene
      expression by the Ishikawa cell line were detected after treatments with E2, P4,
      TAM, and RU486. These transcriptome data provide valuable insight into potential
      biomarkers related to endometrial receptivity, and also facilitate an
      understanding of the molecular changes that take place in the endometrium in the
      early stages of breast cancer treatment and contraception usage.

PMID- 23874808
TI  - Intrinsic TNF/TNFR2 interactions fine-tune the CD8 T cell response to respiratory
      influenza virus infection in mice.
AB  - TNF is an important inflammatory mediator and a target for intervention. TNF is
      produced by many cell types and is involved in innate inflammation as well as
      adaptive immune responses. CD8 T cells produce TNF and can also respond to TNF.
      Deficiency of TNF or TNFR2 has been shown to affect anti-viral immunity. However,
      as the complete knockout of TNF or its receptors has effects on multiple cell
      types as well as on lymphoid architecture, it has been difficult to assess the
      role of TNF directly on T cells during viral infection. Here we have addressed
      this issue by analyzing the effect of CD8 T cell intrinsic TNF/TNFR2 interactions
      during respiratory influenza infection in mice, using an adoptive transfer model
      in which only the T cells lack TNF or TNFR2. During a mild influenza infection,
      the capacity of the responding CD8 T cells to produce TNF increases from day 6
      through day 12, beyond the time of viral clearance. Although T cell intrinsic TNF
      is dispensable for initial expansion of CD8 T cells up to day 9 post infection,
      intrinsic TNF/TNFR2 interactions potentiate contraction of the CD8 T cell
      response in the lung between day 9 and 12 post infection. On the other hand, TNF
      or TNFR2-deficient CD8 T cells in the lung express lower levels of IFN-gamma and
      CD107a per cell than their wild type counterparts. Comparison of TNF levels on
      the TNFR2 positive and negative T cells is consistent with TNF/TNFR2 interactions
      inducing feedback downregulation of TNF production by T cells, with greater
      effects in the lung compared to spleen. Thus CD8 T cell intrinsic TNF/TNFR2
      interactions fine-tune the response to influenza virus in the lung by modestly
      enhancing effector functions, but at the same time potentiating the contraction
      of the CD8 T cell response post-viral clearance. 

PMID- 23874810
TI  - Social media release increases dissemination of original articles in the clinical
      pain sciences.
AB  - A barrier to dissemination of research is that it depends on the end-user
      searching for or 'pulling' relevant knowledge from the literature base. Social
      media instead 'pushes' relevant knowledge straight to the end-user, via blogs and
      sites such as Facebook and Twitter. That social media is very effective at
      improving dissemination seems well accepted, but, remarkably, there is no
      evidence to support this claim. We aimed to quantify the impact of social media
      release on views and downloads of articles in the clinical pain sciences. Sixteen
      PLOS ONE articles were blogged and released via Facebook, Twitter, LinkedIn and
      ResearchBlogging.org on one of two randomly selected dates. The other date served
      as a control. The primary outcomes were the rate of HTML views and PDF downloads
      of the article, over a seven-day period. The critical result was an increase in
      both outcome variables in the week after the blog post and social media release.
      The mean +/- SD rate of HTML views in the week after the social media release was
      18+/-18 per day, whereas the rate during the other three weeks was no more than
      6+/-3 per day. The mean +/- SD rate of PDF downloads in the week after the social
      media release was 4+/-4 per day, whereas the rate during the other three weeks
      was less than 1+/-1 per day (p<0.05 for all comparisons). However, none of the
      recognized measures of social media reach, engagement or virality related to
      either outcome variable, nor to citation count one year later (p>0.3 for all). We
      conclude that social media release of a research article in the clinical pain
      sciences increases the number of people who view or download that article, but
      conventional social media metrics are unrelated to the effect. 

PMID- 23874809
TI  - Unlocked concanavalin A forms amyloid-like fibrils from coagulation of long-lived
      "crinkled" intermediates.
AB  - Understanding the early events during amyloid aggregation processes is crucial to
      single out the involved molecular mechanisms and for designing ad hoc strategies
      to prevent and reverse amyloidogenic disorders. Here, we show that, in conditions
      in which the protein is positively charged and its conformational flexibility is
      enhanced, Concanavalin A leads to fibril formation via a non-conventional
      aggregation pathway. Using a combination of light scattering, circular dichroism,
      small angle X-ray scattering, intrinsic (Tryptophan) and extrinsic (ANS)
      fluorescence and confocal and 2-photon fluorescence microscopy we characterize
      the aggregation process as a function of the temperature. We highlight a multi
      step pathway with the formation of an on-pathway long-lived intermediate and a
      subsequent coagulation of such "crinkled" precursors into amyloid-like fibrils.
      The process results in a temperature-dependent aggregation-coagulation pathway,
      with the late phase of coagulation determined by the interplay between
      hydrophobic and electrostatic forces. Our data provide evidence for the complex
      aggregation pathway for a protein with a highly flexible native conformation. We
      demonstrate the possibility to generate a long-lived intermediate whose
      proportion and occurrence are easily tunable by experimental parameters (i.e.
      temperature). As a consequence, in the case of aggregation processes developing
      through well-defined energy barriers, our results can open the way to new
      strategies to induce more stable in vitro on-pathway intermediate species through
      a minute change in the initial conformational flexibility of the protein. This
      will allow isolating and experimentally studying such transient species, often
      indicated as relevant in neurodegenerative diseases, both in terms of structural
      and cytotoxic properties. 

PMID- 23874812
TI  - Plasminogen activator inhibitor-2 polymorphism associates with recurrent coronary
      event risk in patients with high HDL and C-reactive protein levels.
AB  - The objective of this work was to investigate whether fibrinolysis plays a role
      in establishing recurrent coronary event risk in a previously identified group of
      postinfarction patients. This group of patients was defined as having
      concurrently high levels of high-density lipoprotein cholesterol (HDL-C) and C
      reactive protein (CRP) and was previously demonstrated to be at high-risk for
      recurrent coronary events. Potential risk associations of a genetic polymorphism
      of plasminogen activator inhibitor-2 (PAI-2) were probed as well as potential
      modulatory effects on such risk of a polymorphism of low-density lipoprotein
      receptor related protein (LRP-1), a scavenger receptor known to be involved in
      fibrinolysis in the context of cellular internalization of plasminogen
      activator/plansminogen activator inhibitor complexes. To this end, Cox
      multivariable modeling was performed as a function of genetic polymorphisms of
      PAI-2 (SERPINB, rs6095) and LRP-1 (LRP1, rs1800156) as well as a set of clinical
      parameters, blood biomarkers, and genetic polymorphisms previously demonstrated
      to be significantly and independently associated with risk in the study
      population including cholesteryl ester transfer protein (CETP, rs708272), p22phox
      (CYBA, rs4673), and thrombospondin-4 (THBS4, rs1866389). Risk association was
      demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio
      0.41 per allele, 95% CI 0.20-0.84, p=0.014) along with continued significant risk
      associations for the p22phox and thrombospondin-4 polymorphisms. Additionally,
      further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in
      generating differential risk that was illustrated using Kaplan-Meier survival
      analysis. We conclude from the study that fibrinolysis likely plays a role in
      establishing recurrent coronary risk in postinfarction patients with concurrently
      high levels of HDL-C and CRP as manifested by differential effects on risk by
      polymorphisms of several genes linked to key actions involved in the fibrinolytic
      process. 

PMID- 23874811
TI  - Patterned immobilization of antibodies within roll-to-roll hot embossed polymeric
      microfluidic channels.
AB  - This paper describes a method for the patterned immobilization of capture
      antibodies into a microfluidic platform fabricated by roll-to-roll (R2R) hot
      embossing on poly (methyl methacrylate) (PMMA). Covalent attachment of antibodies
      was achieved by two sequential inkjet printing steps. First, a polyethyleneimine
      (PEI) layer was deposited onto oxygen plasma activated PMMA foil and further
      cross-linked with glutaraldehyde (GA) to provide an amine-reactive aldehyde
      surface (PEI-GA). This step was followed by a second deposition of antibody by
      overprinting on the PEI-GA patterned PMMA foil. The PEI polymer ink was first
      formulated to ensure stable drop formation in inkjet printing and the printed
      films were characterized using atomic force microscopy (AFM) and X-ray
      photoelectron spectroscopy (XPS). Anti-CRP antibody was patterned on PMMA foil by
      the developed method and bonded permanently with R2R hot embossed PMMA
      microchannels by solvent bonding lamination. The functionality of the immobilized
      antibody inside the microfluidic channel was evaluated by fluorescence-based
      sandwich immunoassay for detection of C-reactive protein (CRP). The antibody
      antigen assay exhibited a good level of linearity over the range of 10 ng/ml to
      500 ng/ml (R(2) = 0.991) with a calculated detection limit of 5.2 ng/ml. The
      developed patterning method is straightforward, rapid and provides a versatile
      approach for creating multiple protein patterns in a single microfluidic channel
      for multiplexed immunoassays. 

PMID- 23874813
TI  - The intracellular citrus huanglongbing bacterium, 'Candidatus Liberibacter
      asiaticus' encodes two novel autotransporters.
AB  - Proteins secreted by the type V secretion system (T5SS), known as
      autotransporters, are large extracellular virulence proteins localized to the
      bacterial poles. In this study, we characterized two novel autotransporter
      proteins of 'Candidatus Liberibacter asiaticus' (Las), and redesignated them as
      LasAI and LasAII in lieu of the previous names HyvI and HyvII. As a phloem
      limited, intracellular bacterial pathogen, Las has a significantly reduced genome
      and causes huanglongbing (HLB), a devastating disease of citrus worldwide.
      Bioinformatic analyses revealed that LasAI and LasAII share the structural
      features of an autotransporter family containing large repeats of a passenger
      domain and a unique C-terminal translocator domain. When fused to the GFP gene
      and expressed in E. coli, the LasAI C-terminus and the full length LasAII were
      localized to the bacterial poles, similar to other members of autotransporter
      family. Despite the absence of a typical signal peptide, LasAI was found to
      localize at the cell surface by immuno-dot blot using a monoclonal antibody
      against the partial LasAI protein. Its surface localization was also confirmed by
      the removal of the LasAI antigen using a proteinase K treatment of the intact
      bacterial cells. When co-inoculated with a P19 gene silencing suppressor and
      transiently expressed in tobacco leaves, the GFP-LasAI translocator targeted to
      the mitochondria. This is the first report that Las encodes novel
      autotransporters that target to mitochondria when expressed in the plants. These
      findings may lead to a better understanding of the pathogenesis of this
      intracellular bacterium. 

PMID- 23874814
TI  - Acoustic radiation force impulse imaging for noninvasive evaluation of renal
      parenchyma elasticity: preliminary findings.
AB  - OBJECTIVE: To evaluate the diagnostic value of acoustic radiation force impulse
      (ARFI) to test the elasticity of renal parenchyma by measuring the shear wave
      velocity (SWV) which might be used to detect chronic kidney disease (CKD).
      METHODS: 327 healthy volunteers and 64 CKD patients were enrolled in the study.
      The potential influencing factors and measurement reproducibility were evaluated
      in the healthy volunteers. Correlations between SWV and laboratory tests were
      analyzed in CKD patients.?Receiver-operating characteristic curve (ROC) analyses
      were performed to assess the diagnostic performance of ARFI. RESULTS: The SWV of
      healthy volunteers correlated significantly to age (r = -0.22, P<0.001, n = 327)
      and differed significantly between men and women (2.06+/-0.48 m/s vs. 2.2+/-0.52
      m/s, P = 0.018, n = 327). However, it did not correlate significantly to height,
      weight, body mass index, waistline, kidney dimension and the depth for SWV
      measurement (n = 30). Inter- and intraobserver agreement expressed as intraclass
      coefficient correlation were 0.64 (95% CI: 0.13 to 0.82, P = 0.011) and 0.6 (95%
      CI: 0.31 to 0.81, P = 0.001) (n = 40). The mean SWV in healthy volunteers was
      2.15+/-0.51 m/s, while was 1.81+/-0.43 m/s, 1.79+/-0.29 m/s, 1.81+/-0.44 m/s,
      1.64+/-0.55 m/s, and 1.36+/-0.17 m/s for stage 1, 2, 3, 4 and 5 in CKD patients
      respectively. The SWV was significantly higher for healthy volunteers compared
      with each stage in CKD patients. ARFI could not predict the different stages of
      CKD except stage 5. In CKD patients, SWV correlated to e-GFR (r = 0.3, P =
      0.018), to urea nitrogen (r =  -0.3, P = 0.016), and to creatinine (r =  -0.41, P
      = 0.001). ROC analyses indicated that the area under the ROC curve was 0.752 (95%
      CI: 0.704 to 0.797) (P<0.001). The cut-off value for predicting CKD was 1.88 m/s
      (sensitivity 71.87% and specificity 69.69%). CONCLUSION: ARFI may be a
      potentially useful tool in detecting CKD.

PMID- 23874815
TI  - Spatial structures of the environment and of dispersal impact species
      distribution in competitive metacommunities.
AB  - The correspondence between species distribution and the environment depends on
      species' ability to track favorable environmental conditions (via dispersal) and
      to maintain competitive hierarchy against the constant influx of migrants (mass
      effect) and demographic stochasticity (ecological drift). Here we report a
      simulation study of the influence of landscape structure on species distribution.
      We consider lottery competition for space in a spatially heterogeneous
      environment, where the landscape is represented as a network of localities
      connected by dispersal. We quantified the contribution of neutrality and species
      sorting to their spatial distribution. We found that neutrality increases and the
      strength of species-sorting decreases with the centrality of a community in the
      landscape when the average dispersal among communities is low, whereas the
      opposite was found at elevated dispersal. We also found that the strength of
      species-sorting increases with environmental heterogeneity. Our results
      illustrate that spatial structure of the environment and of dispersal must be
      taken into account for understanding species distribution. We stress the
      importance of spatial geographic structure on the relative importance of niche
      vs. neutral processes in controlling community dynamics. 

PMID- 23874816
TI  - Reaching mothers and babies with early postnatal home visits: the implementation
      realities of achieving high coverage in large-scale programs.
AB  - BACKGROUND: Nearly half of births in low-income countries occur without a skilled
      attendant, and even fewer mothers and babies have postnatal contact with
      providers who can deliver preventive or curative services that save lives.
      Community-based maternal and newborn care programs with postnatal home visits
      have been tested in Bangladesh, Malawi, and Nepal. This paper examines coverage
      and content of home visits in pilot areas and factors associated with receipt of
      postnatal visits. METHODS: Using data from cross-sectional surveys of women with
      live births (Bangladesh 398, Malawi: 900, Nepal: 615), generalized linear models
      were used to assess the strength of association between three factors - receipt
      of home visits during pregnancy, birth place, birth notification - and receipt of
      home visits within three days after birth. Meta-analytic techniques were used to
      generate pooled relative risks for each factor adjusting for other independent
      variables, maternal age, and education. FINDINGS: The proportion of mothers and
      newborns receiving home visits within three days after birth was 57% in
      Bangladesh, 11% in Malawi, and 50% in Nepal. Mothers and newborns were more
      likely to receive a postnatal home visit within three days if the mother received
      at least one home visit during pregnancy (OR2.18, CI1.46-3.25), the birth
      occurred outside a facility (OR1.48, CI1.28-1.73), and the mother reported a CHW
      was notified of the birth (OR2.66, CI1.40-5.08). Checking the cord was the most
      frequently reported action; most mothers reported at least one action for
      newborns. CONCLUSIONS: Reaching mothers and babies with home visits during
      pregnancy and within three days after birth is achievable using existing
      community health systems if workers are available; linked to communities; and
      receive training, supplies, and supervision. In all settings, programs must
      evaluate what community delivery systems can handle and how to best utilize them
      to improve postnatal care access.

PMID- 23874817
TI  - NGF-induced cell differentiation and gene activation is mediated by integrative
      nuclear FGFR1 signaling (INFS).
AB  - Nerve growth factor (NGF) is the founding member of the polypeptide neurotrophin
      family responsible for neuronal differentiation. To determine whether the effects
      of NGF rely upon novel Integrative Nuclear FGF Receptor-1 (FGFR1) Signaling
      (INFS) we utilized the PC12 clonal cell line, a long-standing benchmark model of
      sympathetic neuronal differentiation. We demonstrate that NGF increases
      expression of the fgfr1 gene and promotes trafficking of FGFR1 protein from
      cytoplasm to nucleus by inhibiting FGFR1 nuclear export. Nuclear-targeted
      dominant negative FGFR1 antagonizes NGF-induced neurite outgrowth, doublecortin
      (dcx) expression and activation of the tyrosine hydroxylase (th) gene promoter,
      while active constitutive nuclear FGFR1 mimics the effects of NGF. NGF increases
      the expression of dcx, th, betaIII tubulin, nurr1 and nur77, fgfr1and fibroblast
      growth factor-2 (fgf-2) genes, while enhancing binding of FGFR1and Nur77/Nurr1 to
      those genes. NGF activates transcription from isolated NurRE and NBRE motifs.
      Nuclear FGFR1 transduces NGF activation of the Nur dimer and raises basal
      activity of the Nur monomer. Cooperation of nuclear FGFR1 with Nur77/Nurr1 in NGF
      signaling expands the integrative functions of INFS to include NGF, the first
      discovered pluripotent neurotrophic factor. 

PMID- 23874818
TI  - The role of peroxisome proliferator-activated receptor and effects of its
      agonist, pioglitazone, on a rat model of optic nerve crush: PPARgamma in retinal
      neuroprotection.
AB  - It has been shown that peroxisome proliferators-activated receptor gamma
      (PPARgamma) is beneficial for central nervous system injury. However its role on
      optic nerve injury remains unknown. In the present study, we examined the change
      of PPARgamma expression in rat retina following optic nerve injury and
      investigated the effect of pioglitazone (Pio), a PPARgamma agonist, on retinal
      ganglion cells (RGCs) neuroprotection using a rat optic nerve crush (ONC) model.
      Our results showed that PPARgamma mRNA and protein levels were increased after
      ONC, and most of PPARgamma-immunoreactive cells colocalized with Muller cells.
      Pio treatment significantly enhanced the number of surviving RGCs and inhibited
      RGCs apoptosis induced by ONC. However, when PPARgamma antagonist GW9662 was
      used, these neuroprotective effects were abolished. In addition, pio attenuated
      Muller cell activation after ONC. These results indicate that PPARgamma appears
      to protect RGCs from ONC possibly via the reduction of Muller glial activation.
      It provides evidence that activation of PPARgamma may be a potential alternative
      treatment for RGCs neuroprotection. 

PMID- 23874819
TI  - Postoperative chemoradiotherapy versus postoperative chemotherapy for completely
      resected gastric cancer with D2 Lymphadenectomy: a meta-analysis.
AB  - BACKGROUND: Both chemoradiotherapy and chemotherapy are used in postoperative
      adjuvant therapy for resected gastric cancer. However, it is controversial
      whether chemoradiotherapy or chemotherapy is the optimal strategy for patients
      with gastric cancer after D2 lymphadenectomy. The present meta-analysis aims to
      provide more evidence on the relative benefits of adjuvant therapies in this
      setting. METHODS: We conducted a systematic review of randomized controlled
      trials, extracted time-to-event data using Tierney methods (when not reported),
      and performed meta-analysis to obtain the relative hazards of adjuvant
      chemoradiotherapy to chemotherapy on efficacy and toxicities. RESULTS: A total of
      895 patients from 3 randomized controlled trials were identified for this meta
      analysis. All patients were from Asian countries. Our results showed that
      postoperative chemoradiotherapy significantly improved locoregional recurrence
      free survival [LRRFS: hazard ratio (HR) = 0.53, 95% CI = 0.32-0.87, p = 0.01] and
      disease-free survival (DFS: HR = 0.72, 95% CI = 0.59-0.89, p = 0.002); however,
      the improvement of distant metastasis recurrence-free survival (DMRFS: HR = 0.86;
      95% CI = 0.66-1.11, p = 0.25) and overall survival (OS: HR = 0.79, 95% CI = 0.61
      1.03, p = 0.08) were non-significant. The main grade 3 or 4 toxicities were
      equivalent between the two groups. CONCLUSION: In non-selected Asian patients
      with resected gastric cancer who underwent D2 lymphadenectomy, postoperative
      chemoradiotherapy improved LRRFS and DFS but might not improve OS compared to
      postoperative chemotherapy.

PMID- 23874820
TI  - Evaluation of 41 candidate gene variants for obesity in the EPIC-Potsdam cohort
      by multi-locus stepwise regression.
AB  - OBJECTIVE: Obesity has become a leading preventable cause of morbidity and
      mortality in many parts of the world. It is thought to originate from multiple
      genetic and environmental determinants. The aim of the current study was to
      introduce haplotype-based multi-locus stepwise regression (MSR) as a method to
      investigate combinations of unlinked single nucleotide polymorphisms (SNPs) for
      obesity phenotypes. METHODS: In 2,122 healthy randomly selected men and women of
      the EPIC-Potsdam cohort, the association between 41 SNPs from 18 obesity
      candidate genes and either body mass index (BMI, mean=25.9 kg/m(2), SD=4.1) or
      waist circumference (WC, mean=85.2 cm, SD=12.6) was assessed. Single SNP analyses
      were done by using linear regression adjusted for age, sex, and other covariates.
      Subsequently, MSR was applied to search for the 'best' SNP combinations.
      Combinations were selected according to specific AICc and p-value criteria. Model
      uncertainty was accounted for by a permutation test. RESULTS: The strongest
      single SNP effects on BMI were found for TBC1D1 rs637797 (beta = -0.33, SE=0.13),
      FTO rs9939609 (beta=0.28, SE=0.13), MC4R rs17700144 (beta=0.41, SE=0.15), and
      MC4R rs10871777 (beta=0.34, SE=0.14). All these SNPs showed similar effects on
      waist circumference. The two 'best' six-SNP combinations for BMI (global p-value=
      3.45?10(-6) and 6.82?10(-6)) showed effects ranging from -1.70 (SE=0.34) to 0.74
      kg/m(2) (SE=0.21) per allele combination. We selected two six-SNP combinations on
      waist circumference (global p-value = 7.80?10(-6) and 9.76?10(-6)) with an allele
      combination effect of -2.96 cm (SE=0.76) at maximum. Additional adjustment for
      BMI revealed 15 three-SNP combinations (global p-values ranged from 3.09?10(-4)
      to 1.02?10(-2)). However, after carrying out the permutation test all SNP
      combinations lost significance indicating that the statistical associations might
      have occurred by chance. CONCLUSION: MSR provides a tool to search for risk
      related SNP combinations of common traits or diseases. However, the search
      process does not always find meaningful SNP combinations in a dataset.

PMID- 23874821
TI  - Activation of Egr-1 in human lung epithelial cells exposed to silica through
      MAPKs signaling pathways.
AB  - The alveolar type II epithelial cell, regarded historically as a key target cell
      in initial injury by silica, now appears to be important in both defense from
      lung damage as well as elaboration of chemokines and cytokines. The molecular
      basis for silica-induced epithelial cell injury is poorly understood. In this
      study we explored the activation of nuclear factor Egr-1 and related signal
      pathway. Human II alveolar epithelial line A549 cells were exposed to silica for
      indicated time to assay the expression and activation of Egr-1 and upstream
      MAPKs. Immunofluorescence, western-blot techniques, RT-PCR, Electrophoretic
      mobility shift assay (EMSA), transient transfection assay, kinase inhibitor
      experiments were performed. It was found that the expression of Egr-1 at mRNA and
      protein level was significantly increased in A549 cells after administration with
      silica and the activity of Egr-1 peaked by silica treatment for 60 minutes.
      Furthermore, phosphorylated-ERK1/2, P38 MAPKs (the upstream kinase of Egr-1)
      ballooned during 15-30minutes, 30-60minutes respectively after silica exposure in
      A549 cells. By administration of ERK1/2, P38 inhibitor, the expression and
      transcription of Egr-1 were both markedly decreased. But PKC inhibitor did not
      prevent the increase of Egr-1. These results indicated Egr-1 played a critical
      role in silica-induced pulmonary fibrosis in an ERK1/2, P38 MAPKs-dependent
      manner, which suggests Egr-1 is an essential regulator in silicosis, and
      underlines a new molecular mechanism for fibrosis induced by silica. 

PMID- 23874822
TI  - Factors associated with adenoma detection rate and diagnosis of polyps and
      colorectal cancer during colonoscopy in France: results of a prospective,
      nationwide survey.
AB  - INTRODUCTION: Colonoscopy can prevent deaths due to colorectal cancer (CRC)
      through early diagnosis or resection of colonic adenomas. We conducted a
      prospective, nationwide study on colonoscopy practice in France. METHODS: An
      online questionnaire was administered to 2,600 French gastroenterologists. Data
      from all consecutive colonoscopies performed during one week were collected. A
      statistical extrapolation of the results to a whole year was performed, and
      factors potentially associated with the adenoma detection rate (ADR) or the
      diagnosis of polyps or cancer were assessed. RESULTS: A total of 342
      gastroenterologists, representative of the overall population of French
      gastroenterologists, provided data on 3,266 colonoscopies, corresponding to
      1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The
      indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and
      38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The
      ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors
      associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001),
      personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001,
      respectively), and positive fecal occult blood test (p=0.0005). The prevalence of
      CRC was three times higher in patients with their first colonoscopy (4.2% vs.
      1.4%; p<0.0001). CONCLUSIONS: For the first time in France, we report nationwide
      prospective data on colonoscopy practice, including histological results. We
      found an average ADR of 17.7%, and observed reduced CRC incidence in patients
      with previous colonoscopy.

PMID- 23874823
TI  - N-acetylcysteine and allopurinol confer synergy in attenuating myocardial
      ischemia injury via restoring HIF-1alpha/HO-1 signaling in diabetic rats.
AB  - OBJECTIVES: To determine whether or not the antioxidants N-acetylcysteine (NAC)
      and allopurinol (ALP) confer synergistic cardioprotection against myocardial
      ischemia/reperfusion (MI/R) injury by stabilizing hypoxia inducible factor 1alpha
      (HIF-1alpha)/heme oxygenase 1 (HO-1) signaling in diabetic myocardium. METHODS:
      Control or diabetic [streptozotocin (STZ)-induced] Sprague Dawley rats received
      vehicle or NAC, ALP or their combination for four weeks starting one week after
      STZ injection. The animals were then subjected to thirty minutes of coronary
      artery occlusion followed by two hours reperfusion in the absence or presence of
      the selective HO-1 inhibitor, tin protoporphyrin-IX (SnPP-IX) or the HIF-1alpha
      inhibitor 2-Methoxyestradiol (2ME2). Cardiomyocytes exposed to high glucose were
      subjected to hypoxia/re-oxygenation in the presence or absence of HIF-1alpha and
      HO-1 achieved by gene knock-down with related siRNAs. RESULTS: Myocardial and
      plasma levels of 15-F2t-isoprostane, an index of oxidative stress, were
      significantly increased in diabetic rats while cardiac HO-1 protein and activity
      were reduced; this was accompanied with reduced cardiac protein levels of HIF
      1alpha, and increased post-ischemic myocardial infarct size and cellular injury.
      NAC and ALP given alone and in particular their combination normalized cardiac
      levels of HO-1 and HIF-1alpha protein expression and prevented the increase in 15
      F2t-isoprostane, resulting in significantly attenuated post-ischemic myocardial
      infarction. NAC and ALP also attenuated high glucose-induced post-hypoxic
      cardiomyocyte death in vitro. However, all the above protective effects of NAC
      and ALP were cancelled either by inhibition of HO-1 or HIF-1alpha with SnPP-IX
      and 2ME2 in vivo or by HO-1 or HIF-1alpha gene knock-down in vitro. CONCLUSION:
      NAC and ALP confer synergistic cardioprotection in diabetes via restoration of
      cardiac HIF-1alpha and HO-1 signaling.

PMID- 23874825
TI  - Testing the accuracy of different A-axis types for measuring the orientation of
      bones in the archaeological and paleontological record.
AB  - Orientation of archaeological and paleontological materials plays a prominent
      role in the interpretation of site formation processes. Allochthony and
      authochthony are frequently assumed from orientation patterns or lack thereof.
      Although it is still debated to what extent orientation of items can be produced
      in original depositional contexts, the recent use of GIS tools to measure
      orientations has highlighted several ways of reproducing A-axes with which to
      address these taphonomic issues. In the present study, the three most relevant A
      axis types are compared to test their accuracy in reproducing water current
      direction. Although results may be similar in specific bone shapes, differences
      are important in other shapes. As known in engineering working with wind and
      fluid mechanics (developing shape optimization), longitudinal symmetrical axes
      (LSA) are the one that best orient structures against or in the same direction of
      wind and water. The present work shows that this is also the case for bones
      (regardless of shape), since LSA produce the most accurate estimates of flow
      direction. This has important consequences for the interpretation of orientation
      patterns at sites, since this type of axis is still not properly reproduced by
      GIS available tools. 

PMID- 23874824
TI  - Incidence of liver damage of uncertain origin in HIV patients not co-infected
      with HCV/HBV.
AB  - BACKGROUND AND AIMS: Several studies have reported that a significant number of
      HIV patients not co-infected with HCV/HBV develop liver damage of uncertain
      origin (LDUO). The objective of our study was to evaluate the incidence of and
      risk factors for the development of LDUO in HIV infected patients not co-infected
      with HCV/HBV. METHODS: Prospective longitudinal study that included HIV-infected
      patients free of previous liver damage and viral hepatitis B or C co-infections.
      Patients were followed up at 6-monthly intervals. Liver stiffness was measured at
      each visit. Abnormal liver stiffness (ALS) was defined as a liver stiffness value
      greater than 7.2 kPa at two consecutive measurements. For patients who developed
      ALS, a protocol was followed to diagnose the cause of liver damage. Those
      patients who could not be diagnosed with any specific cause of liver disease were
      diagnosed as LDUO and liver biopsy was proposed. RESULTS: 210 patients matched
      the inclusion criteria and were included. 198 patients completed the study. After
      a median (Q1-Q3) follow-up of 18 (IQR 12-26) months, 21 patients (10.6%)
      developed ALS. Of these, fifteen patients were diagnosed as LDUO. The incidence
      of LDUO was 7.64 cases/100 patient-years. Histological studies were performed on
      ten (66.6%) patients and all showed liver steatosis. A higher HOMA-IR value and
      body mass index were independently associated with the development of LDUO.
      CONCLUSION: We found a high incidence of LDUO in HIV-infected patients associated
      with metabolic risk factors. The leading cause of LDUO in our study was non
      alcoholic fatty liver disease.

PMID- 23874826
TI  - Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg
      and wild type mice.
AB  - Spaceflight is associated with several health issues including diminished immune
      efficiency. Effects of long-term spaceflight on selected immune parameters of
      wild type (Wt) and transgenic mice over-expressing pleiotrophin under the human
      bone-specific osteocalcin promoter (PTN-Tg) were examined using the novel Mouse
      Drawer System (MDS) aboard the International Space Station (ISS) over a 91 day
      period. Effects of this long duration flight on PTN-Tg and Wt mice were
      determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt
      mice. Levels of interleukin-2 (IL-2) and transforming growth factor-beta1 (TGF
      beta1) were measured in mucosal and systemic tissues of Wt and PTN-Tg mice.
      Colonic contents were also analyzed to assess potential effects on the gut
      microbiota, although no firm conclusions could be made due to constraints imposed
      by the MDS payload and the time of sampling. Spaceflight-associated differences
      were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF
      beta1 relative to ground controls. Total colonic TGF-beta1 levels were lower in
      Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse
      had lower levels of IL-2 and TGF-beta1 compared to the Wt ground control in both
      the inguinal and brachial lymph nodes, however this pattern was not consistently
      observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active
      TGF-beta1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results
      of this study suggest compartmentalized effects of spaceflight and on immune
      parameters in mice. 

PMID- 23874827
TI  - The role of RING box protein 1 in mouse oocyte meiotic maturation.
AB  - RING box protein-1 (RBX1) is an essential component of Skp1-cullin-F-box protein
      (SCF) E3 ubiquitin ligase and participates in diverse cellular processes by
      targeting various substrates for degradation. However, the physiological function
      of RBX1 in mouse oocyte maturation remains unknown. Here, we examined the
      expression, localization and function of RBX1 during mouse oocyte meiotic
      maturation. Immunofluorescence analysis showed that RBX1 displayed dynamic
      distribution during the maturation process: it localized around and migrated
      along with the spindle and condensed chromosomes. Rbx1 knockdown with the
      appropriate siRNAs led to a decreased rate of first polar body extrusion and most
      oocytes were arrested at metaphase I. Moreover, downregulation of Rbx1 caused
      accumulation of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome
      (APC/C), which is required for mouse meiotic maturation. In addition, we found
      apparently increased expression of the homologue disjunction-associated protein
      securin and cyclin B1, which are substrates of APC/C E3 ligase and need to be
      degraded for meiotic progression. These results indicate the essential role of
      the SCF(betaTrCP)-EMI1-APC/C axis in mouse oocyte meiotic maturation. In
      conclusion, we provide evidence for the indispensable role of RBX1 in mouse
      oocyte meiotic maturation. 

PMID- 23874828
TI  - Successful human infection with P. falciparum using three aseptic Anopheles
      stephensi mosquitoes: a new model for controlled human malaria infection.
AB  - Controlled human malaria infection (CHMI) is a powerful method for assessing the
      efficacy of anti-malaria vaccines and drugs targeting pre-erythrocytic and
      erythrocytic stages of the parasite. CHMI has heretofore required the bites of 5
      Plasmodium falciparum (Pf) sporozoite (SPZ)-infected mosquitoes to reliably
      induce Pf malaria. We reported that CHMI using the bites of 3 PfSPZ-infected
      mosquitoes reared aseptically in compliance with current good manufacturing
      practices (cGMP) was successful in 6 participants. Here, we report results from a
      subsequent CHMI study using 3 PfSPZ-infected mosquitoes reared aseptically to
      validate the initial clinical trial. We also compare results of safety,
      tolerability, and transmission dynamics in participants undergoing CHMI using 3
      PfSPZ-infected mosquitoes reared aseptically to published studies of CHMI using 5
      mosquitoes. Nineteen adults aged 18-40 years were bitten by 3 Anopheles stephensi
      mosquitoes infected with the chloroquine-sensitive NF54 strain of Pf. All 19
      participants developed malaria (100%); 12 of 19 (63%) on Day 11. The mean pre
      patent period was 258.3 hours (range 210.5-333.8). The geometric mean parasitemia
      at first diagnosis by microscopy was 9.5 parasites/uL (range 2-44). Quantitative
      polymerase chain reaction (qPCR) detected parasites an average of 79.8 hours
      (range 43.8-116.7) before microscopy. The mosquitoes had a geometric mean of
      37,894 PfSPZ/mosquito (range 3,500-152,200). Exposure to the bites of 3
      aseptically-raised, PfSPZ-infected mosquitoes is a safe, effective procedure for
      CHMI in malaria-naive adults. The aseptic model should be considered as a new
      standard for CHMI trials in non-endemic areas. Microscopy is the gold standard
      used for the diagnosis of Pf malaria after CHMI, but qPCR identifies parasites
      earlier. If qPCR continues to be shown to be highly specific, and can be made to
      be practical, rapid, and standardized, it should be considered as an alternative
      for diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00744133 NCT00744133.

PMID- 23874829
TI  - Elucidating interactions and conductivity of newly synthesised low bandgap
      polymer with protic and aprotic ionic liquids.
AB  - In this paper, we have examined the conductivity and interaction studies of
      ammonium and imidazolium based ionic liquids (ILs) with the newly synthesised low
      bandgap polymer (Poly(2-heptadecyl-4-vinylthieno[3,4-d]thiazole) (PHVTT)). Use of
      low bandgap polymers is the most suitable way to harvest a broader spectrum of
      solar radiations for solar cells. But, still there is lack of most efficient low
      bandgap polymer. In order to solve this problem, we have synthesised a new low
      bandgap polymer and investigated its interaction with the ILs to enhance its
      conductivity. ILs may undergo almost unlimited structural variations; these
      structural variations have attracted extensive attention in polymer studies. The
      aim of present work is to illustrate the state of art progress of implementing
      the interaction of ILs (protic and aprotic ILs) with newly synthesised low
      bandgap polymer. In addition to this, our UV-Vis spectroscopy, confocal Raman
      spectroscopy and FT-IR spectroscopy results have revealed that all studied ILs
      (tributylmethylammonium methyl sulfate ([N1444][MeSO4] from ammonium family) and
      1-methylimidazolium chloride ([Mim]Cl, and 1-butyl-3-methylimidazolium chloride
      ([Bmim]Cl from imidazolium family) have potential to interact with polymer. Our
      semi empirical calculation with help of Hyperchem 7 shows that protic IL
      ([Mim]Cl) interacts strongly with the low bandgap polymer through the H-bonding.
      Further, protic ILs shows enhanced conductivity than aprotic ILs in association
      with low bandgap polymer. This study provides the combined effect of low bandgap
      polymer and ILs that may generate many theoretical and experimental
      opportunities. 

PMID- 23874830
TI  - Efficacy of histone deacetylase and estrogen receptor inhibition in breast cancer
      cells due to concerted down regulation of Akt.
AB  - Hormonal therapy resistance remains a considerable barrier in the treatment of
      breast cancer. Activation of the Akt-PI3K-mTOR pathway plays an important role in
      hormonal therapy resistance. Our recent preclinical and clinical studies showed
      that the addition of a histone deacetylase inhibitor re-sensitized hormonal
      therapy resistant breast cancer to tamoxifen. As histone deacetylases are key
      regulators of Akt, we evaluated the effect of combined treatment with the histone
      deacetylase inhibitor PCI-24781 and tamoxifen on Akt in breast cancer cells. We
      demonstrate that while both histone deacetylase and estrogen receptor inhibition
      down regulate AKT mRNA and protein, their concerted effort results in down
      regulation of AKT activity with induction of cell death. Histone deacetylase
      inhibition exerts its effect on AKT mRNA through an estrogen receptor-dependent
      mechanism, primarily down regulating the most abundant isoform AKT1. Although
      siRNA depletion of AKT modestly induces cell death, when combined with an anti
      estrogen, cytotoxicity is significantly enhanced. Thus, histone deacetylase
      regulation of AKT mRNA is a key mediator of this therapeutic combination and may
      represent a novel biomarker for predicting response to this regimen. 

PMID- 23874831
TI  - Platinum-based versus non-platinum-based chemotherapy as first line treatment of
      inoperable, advanced gastric adenocarcinoma: a meta-analysis.
AB  - BACKGROUND: Although the platinum regimen is adopted widely nowadays in spite of
      the excessive side effects, there is still no international standard for
      palliative chemotherapy of advanced gastric cancer. This meta-analysis assessed
      the efficacy and tolerability of platinum versus non-platinum chemotherapy as
      first-line palliative treatment in patients with inoperable, advanced gastric
      cancer. METHODS: Randomized phase II and III clinical trials on first-line
      palliative chemotherapy in inoperable, advanced gastric cancer were identified by
      electronic searches of PubMed, Embase, and the Cochrane Controlled Trial
      Register, and hand searches of relevant abstract books and reference lists.
      Response rates, overall survival, and toxicity were analyzed. Depending on
      whether new-generation agents (S-1, taxanes and irinotecan) were utilized, the
      non-platinum regimens were divided into two subgroup. RESULTS: Compared to non
      platinum regimens containing new-generation agents, the use of platinum-based
      regimens was associated with better response (risk ratio (RR) = 1.94, 95%CI[1.48,
      2.55], p<0.001), an increase of overall survival (hazard ratio (HR) = 0.85,
      95%CI[0.78, 0.92], p<0.001), a higher risk of hematological and non-hematological
      toxicity. No statistically significant increase in response (RR = 1.03, 95%CI
      [0.85, 1.24], p = 0.76) or overall survival (HR = 1.07, 95%CI [0.88, 1.30], p =
      0.49) was found when platinum therapies were compared to new-generation agent
      based combination regimens. The toxicity of platinum-based regimens was
      significantly higher for hematologic toxicity, nausea and vomiting, and
      neurotoxicity, but not for diarrhea and toxic death rate. CONCLUSION: New
      generation agent based combination regimens achieved similar response rate and
      overall survival as platinum-based therapy that had generally higher side
      effects. S-1, taxanes and irinotecan seemed to be valid options for patients with
      inoperable, advanced gastric cancer as first-line chemotherapy.

PMID- 23874832
TI  - Differential impact of two risk communications on antipsychotic prescribing to
      people with dementia in Scotland: segmented regression time series analysis 2001
      2011.
AB  - BACKGROUND: Regulatory risk communications are an important method for
      disseminating drug safety information, but their impact varies. Two significant
      UK risk communications about antipsychotic use in older people with dementia were
      issued in 2004 and 2009. These varied considerably in their content and
      dissemination, allowing examination of their differential impact. METHODS:
      Segmented regression time-series analysis 2001-2011 for people aged >=65 years
      with dementia in 87 Scottish general practices, examining the impact of two pre
      specified risk communications in 2004 and 2009 on antipsychotic and other
      psychotropic prescribing. RESULTS: The percentage of people with dementia
      prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an
      estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk
      communication was sent directly to all prescribers, and specifically recommended
      review of all patients prescribed relevant drugs. It was associated with an
      immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI -6.6 to
      -5.2) and a change to a stable level of prescribing subsequently. The 2009 risk
      communication was disseminated in a limited circulation bulletin, and only
      specifically recommended avoiding initiation if possible. There was no immediate
      associated impact, but it was associated with a significant decline in
      prescribing subsequently which appeared driven by a decline in initiation, with
      the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5%
      in Q1 2011. There was no widespread substitution of antipsychotics with other
      psychotropic drugs. CONCLUSIONS: The two risk communications were associated with
      reductions in antipsychotic use, in ways which were compatible with marked
      differences in their content and dissemination. Further research is needed to
      ensure that the content and dissemination of regulatory risk communications is
      optimal, and to track their impact on intended and unintended outcomes. Although
      rates are falling, antipsychotic prescribing in dementia in Scotland remains
      unacceptably high.

PMID- 23874833
TI  - Anorectal transplantation in human cadavers: mock anorectal allotransplantation.
AB  - BACKGROUND: Anorectal transplantation is a method for patients who have lost
      their anorectal function or suffer from congenital anorectal dysfunction to
      recover this function, and this has been investigated in experimental animal
      models using pigs, dogs, and rats. In this study, we performed an examination of
      anorectal transplantation in human cadavers to investigate whether this procedure
      could be performed in patients. METHODS: A 77-year-old woman cadaver 1 was used
      as the donor and a 98-year-old woman cadaver 2 was used as the recipient.
      Initially, abdominoperineal excision of the anus and rectum (the Miles'
      operation) was performed on the recipient. Next, an anorectal graft containing
      the pudendal nerve (PN), pudendal artery (PA), pudendal vein (PV), inferior
      mesenteric artery (IMA), and inferior mesenteric vein (IMV) was harvested from
      the donor. The donor graft was transplanted into the recipient by intestinal
      anastomosis and microneurovascular anastomoses orthotopically. RESULTS: The
      diameters of the PN (right/left), IMA, and IMV were 2.5 mm/2.5 mm, 2.0 mm, and
      1.5 mm, respectively, in cadaver 1, and 2.0 mm/2.0 mm, 2.0 mm, and 2.0 mm,
      respectively, in cadaver 2. The length of the PN, PA, PV, IMA, and IMV in the
      graft was sufficient to allow proper anastomosis. CONCLUSION: This preliminary
      study indicated that human anorectal transplantation was possible anatomically
      and technically. We anticipate our study will aid in the potential future
      application of this procedure to human patients.

PMID- 23874834
TI  - Cell stress promotes the association of phosphorylated HspB1 with F-actin.
AB  - Previous studies have suggested that the small heat shock protein, HspB1, has a
      direct influence on the dynamics of cytoskeletal elements, in particular,
      filamentous actin (F-actin) polymerization. In this study we have assessed the
      influence of HspB1 phosphorylation on its interaction(s) with F-actin. We first
      determined the distribution of endogenous non-phosphorylated HspB1,
      phosphorylated HspB1 and F-actin in neuroendocrine PC12 cells by
      immunocytochemistry and confocal microscopy. We then investigated a potential
      direct interaction between HspB1 with F-actin by precipitating F-actin directly
      with biotinylated phalloidin followed by Western analyses; the reverse
      immunoprecipitation of HspB1 was also carried out. The phosphorylation influence
      of HspB1 in this interaction was investigated by using pharmacologic inhibition
      of p38 MAPK. In control cells, HspB1 interacts with F-actin as a predominantly
      non-phosphorylated protein, but subsequent to stress there is a redistribution of
      HspB1 to the cytoskeletal fraction and a significantly increased association of
      pHspB1 with F-actin. Our data demonstrate HspB1 is found in a complex with F
      actin both in phosphorylated and non-phosphorylated forms, with an increased
      association of pHspB1 with F-actin after heat stress. Overall, our study combines
      both cellular and biochemical approaches to show cellular localization and direct
      demonstration of an interaction between endogenous HspB1 and F-actin using
      methodolgy that specifically isolates F-actin. 

PMID- 23874835
TI  - Preference of a polyphagous mirid bug, Apolygus lucorum (Meyer-Dur) for flowering
      host plants.
AB  - Apolygus lucorum (Meyer-Dur) (Hemiptera: Miridae) is one of the most important
      herbivores in a broad range of cultivated plants, including cotton, cereals,
      vegetables, and fruit crops in China. In this manuscript, we report on a 6-year
      long study in which (adult) A. lucorum abundance was recorded on 174 plant
      species from 39 families from early July to mid-September. Through the study
      period per year, the proportion of flowering plants exploited by adult A. lucorum
      was significantly greater than that of non-flowering plants. For a given plant
      species, A. lucorum adults reached peak abundance at the flowering stage, when
      the plant had the greatest attraction to the adults. More specifically, mean
      adult abundance on 26 species of major host plants and their relative standard
      attraction were 10.3-28.9 times and 9.3-19.5 times higher at flowering stage than
      during non-flowering periods, respectively. Among all the tested species, A.
      lucorum adults switched food plants according to the succession of flowering
      plant species. In early July, A. lucorum adults preferred some plant species in
      bloom, such as Vigna radiata, Gossypium hirsutum, Helianthus annuus and
      Chrysanthemum coronarium; since late July, adults dispersed into other flowering
      hosts (e.g. Ricinus communis, Impatiens balsamina, Humulus scandens, Ocimum
      basilicum, Agastache rugosus and Coriandrum sativum); in early September, they
      largely migrated to flowering Artemisia spp. (e.g. A. argyi, A. lavandulaefolia,
      A. annua and A. scoparia). Our findings underscore the important role of
      flowering plays in the population dynamics and inter-plant migration of this
      mirid bug. Also, our work helps understand evolutionary aspects of host plant use
      in polyphagous insects such as A. lucorum, and provides baseline information for
      the development of sustainable management strategies of this key agricultural
      pest. 

PMID- 23874836
TI  - Silencing of Pokemon enhances caspase-dependent apoptosis via fas- and
      mitochondria-mediated pathways in hepatocellular carcinoma cells.
AB  - The role of Pokemon (POK erythroid myeloid ontogenic actor), a recently
      identified POK transcription factor with proto-oncogenic activity, in
      hepatocellular carcinogenesis has only been assessed by a few studies. Our
      previous study revealed that Pokemon is overexpressed in hepatocellular
      carcinomas (HCC) and promotes HCC cell proliferation and migration via an AKT-
      and ERK- dependent manner. In the present study, we used the TUNEL assay and FACS
      analysis to demonstrate that oxaliplatin induced apoptosis was significantly
      increased in cells with silenced Pokemon. Western blots showed that p53
      expression and phosphorylation were significantly increased in Pokemon defective
      cells, thereby initiating the mitochondria-mediated and death receptor-mediated
      apoptotic pathways. In the mitochondria-mediated pathway, expression of pro
      apoptotic Bcl-2 family members (including Bad, Bid, Bim and Puma) as well as AIF
      was increased and decreasing the mitochondrial membrane potential resulted in
      cytochrome C released from mitochondrial in HepG2 si-Pokemon cells. In addition,
      upon oxaliplatin treatment of Pokemon-silenced cells, the FAS receptor, FADD and
      their downstream targets caspase-10 and caspase-8 were activated, causing
      increased release of caspase-8 active fragments p18 and p10. Increased activated
      caspase-8-mediated cleavage and activation of downstream effector caspases such
      as caspase-9 and caspase-3 was observed in HepG2 si-Pokemon cells as compared to
      control. Therefore, Pokemon might serve as an important mediator of crosstalk
      between intrinsic and extrinsic apoptotic pathways in HCC cells. Moreover, our
      findings suggest that Pokemon could be an attractive therapeutic target gene for
      human cancer therapy. 

PMID- 23874837
TI  - Overexpressed microRNA-182 promotes proliferation and invasion in prostate cancer
      PC-3 cells by down-regulating N-myc downstream regulated gene 1 (NDRG1).
AB  - MicroRNAs, non-coding 20-22 nucleotide single-stranded RNAs, result in
      translational repression or degradation and gene silencing of their target genes,
      and significantly contribute to the regulation of gene expression. In the current
      study, we report that miR-182 expression was significantly upregulated in
      prostate cancer tissues and four cell lines, compared to benign prostatic
      hyperplasia tissues and normal prostatic epithelial (RWPE-1) cells. Ectopic
      overexpression of miR-182 significantly promotes the proliferation, increases the
      invasion, promotes the G1/S cell cycle transition and reduces early apotosis of
      PC-3 cells, while suppression of miR-182 decreased the proliferation and
      invasion, inhibits the G1/S cell cycle transition and increase early apotosis of
      PC-3 cells. Additionally, we demonstrated that miR-182 could downregulate
      expression of NDRG1 by directly targeting the NDRG1 3'-untranslated region. In
      conclusion, our results suggest that miR-182 plays an important role in the
      proliferation of human prostate cancer cells by directly suppressing the tumor
      supressor gene NDRG1. We uncovered a new epigenetic regulation of NDRG1. 

PMID- 23874838
TI  - Oral neutrophil transcriptome changes result in a pro-survival phenotype in
      periodontal diseases.
AB  - BACKGROUND: Periodontal diseases are inflammatory processes that occur following
      the influx of neutrophils into the periodontal tissues in response to the
      subgingival bacterial biofilm. Current literature suggests that while neutrophils
      are protective and prevent bacterial infections, they also appear to contribute
      to damage of the periodontal tissues. In the present study we compare the gene
      expression profile changes in neutrophils as they migrate from the circulation
      into the oral tissues in patients with chronic periodontits and matched healthy
      subjects. We hypothesized that oral neutrophils in periodontal disease patients
      will display a disease specific transcriptome that differs from the oral
      neutrophil of healthy subjects. METHODS: Venous blood and oral rinse samples were
      obtained from healthy subjects and chronic periodontitis patients for neutrophil
      isolation. mRNA was isolated from the neutrophils, and gene expression microarray
      analysis was completed. Results were confirmed for specific genes of interest by
      qRT-PCR and Western Blot analysis. RESULTS AND DISCUSSION: Chronic periodontitis
      patients presented with increased recruitment of neutrophils to the oral cavity.
      Gene expression analysis revealed differences in the expression levels of genes
      from several biological pathways. Using hierarchical clustering analysis, we
      found that the apoptosis network was significantly altered in patients with
      chronic inflammation in the oral cavity, with up-regulation of pro-survival
      members of the Bcl-2 family and down-regulation of pro-apoptosis members in the
      same compartment. Additional functional analysis confirmed that the percentages
      of viable neutrophils are significantly increased in the oral cavity of chronic
      periodontitis patients. CONCLUSIONS: Oral neutrophils from patients with
      periodontal disease displayed an altered transcriptome following migration into
      the oral tissues. This resulted in a pro-survival neutrophil phenotype in chronic
      periodontitis patients when compared with healthy subjects, resulting in a longer
      lived neutrophil. This is likely to impact the severity and length of the
      inflammatory response in this oral disease.

PMID- 23874839
TI  - Platelet lysates produced from expired platelet concentrates support growth and
      osteogenic differentiation of mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells are promising candidates in regenerative cell
      therapy. Conventional culture methods involve the use of animal substances,
      specifically fetal bovine serum as growth supplement. Since the use of animal
      derived products is undesirable for human applications, platelet lysates produced
      from human platelets are an attractive alternative. This is especially true if
      platelet lysates from already approved transfusion units at blood banks can be
      utilized. The purpose of this study was to produce human platelet lysates from
      expired, blood bank-approved platelet concentrates and evaluate their use as
      growth supplement in the culture of mesenchymal stem cells. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, bone marrow-derived mesenchymal stem cells were cultured
      with one of three culture supplements; fetal bovine serum, lysates from freshly
      prepared human platelet concentrates, or lysates from expired human platelet
      concentrates. The effects of these platelet-derived culture supplements on basic
      mesenchymal stem cell characteristics were evaluated. All cultures maintained the
      typical mesenchymal stem cell surface marker expression, trilineage
      differentiation potential, and the ability to suppress in vitro immune responses.
      However, mesenchymal stem cells supplemented with platelet lysates proliferated
      faster than traditionally cultured cells and increased the expression of the
      osteogenic marker gene RUNX-2; yet no difference between the use of fresh and
      expired platelet concentrates was observed. CONCLUSION/SIGNIFICANCE: Our findings
      suggest that human platelet lysates produced from expired platelet concentrates
      can be used as an alternative to fetal bovine serum for mesenchymal stem cell
      culture to the same extent as lysates from fresh platelets.

PMID- 23874840
TI  - Osteoprotegerin inhibits calcification of vascular smooth muscle cell via down
      regulation of the Notch1-RBP-Jkappa/Msx2 signaling pathway.
AB  - OBJECTIVE: Vascular calcification is a common pathobiological process which
      occurs among the elder population and in patients with diabetes and chronic
      kidney disease. Osteoprotegerin, a secreted glycoprotein that regulates bone
      mass, has recently emerged as an important regulator of the development of
      vascular calcification. However, the mechanism is not fully understood. The
      purpose of this study is to explore novel signaling mechanisms of osteoprotegerin
      in the osteoblastic differentiation in rat aortic vascular smooth muscle cells
      (VSMCs). METHODS AND RESULTS: VSMCs were isolated from thoracic aorta of Sprague
      Dawley rats. Osteoblastic differentiation of VSMCs was induced by an osteogenic
      medium. We confirmed by Von Kossa staining and direct cellular calcium
      measurement that mineralization was significantly increased in VSMCs cultured in
      osteogenic medium; consistent with an enhanced alkaline phosphatase activity.
      This osteoblastic differentiation in VSMCs was significantly reduced by the
      addition of osteoprotegerin in a dose responsive manner. Moreover, we identified,
      by real-time qPCR and western blotting, that expression of Notch1 and RBP-Jkappa
      were significantly up-regulated in VSMCs cultured in osteogenic medium at both
      the mRNA and protein levels, these effects were dose-dependently abolished by the
      treatment of osteoprotegerin. Furthermore, we identified that Msx2, a downstream
      target of the Notch1/RBP-Jkappa signaling, was markedly down-regulated by the
      treatment of osteoprotegerin. CONCLUSION: Osteoprotegerin inhibits vascular
      calcification through the down regulation of the Notch1-RBP-Jkappa signaling
      pathway.

PMID- 23874841
TI  - MicroRNA-200a regulates Grb2 and suppresses differentiation of mouse embryonic
      stem cells into endoderm and mesoderm.
AB  - The mechanisms by which microRNAs (miRNAs) affect cell fate decisions remain
      poorly understood. Herein, we report that miR-200a can suppress the
      differentiation of mouse embryonic stem (ES) cells into endoderm and mesoderm.
      Interestingly, miR-200a directly targets growth factor receptor-bound protein 2
      (Grb2), which is a key adaptor in the Erk signaling pathway. Furthermore, high
      levels of miR-200a dramatically decrease Grb2 levels and suppress the appearance
      of mesoderm and endoderm lineages in embryoid body formation, as well as
      suppressing the activation of Erk. Finally, Grb2 supplementation significantly
      rescues the miR-200a-induced layer-formation bias and the Erk suppression.
      Collectively, our results demonstrate that miR-200a plays critical roles in ES
      cell lineage commitment by directly regulating Grb2 expression and Erk signaling.

PMID- 23874842
TI  - Differentially expressed genes in the pre-eclamptic placenta: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To systematically review the literature on human gene expression data
      of placental tissue in pre-eclampsia and to characterize a meta-signature of
      differentially expressed genes in order to identify novel putative diagnostic
      markers. DATA SOURCES: Medline through 11 February 2011 using MeSH terms and
      keywords related to placenta, gene expression and gene expression arrays; GEO
      database using the term "placent*"; and reference lists of eligible primary
      studies, without constraints. METHODS: From 1068 studies retrieved from the
      search, we included original publications that had performed gene expression
      array analyses of placental tissue in the third trimester and that reported on
      differentially expressed genes in pre-eclampsia versus normotensive controls. Two
      reviewers independently identified eligible studies, extracted descriptive and
      gene expression data and assessed study quality. Using a vote-counting method
      based on a comparative meta-profiling algorithm, we determined a meta-signature
      that characterizes the significant intersection of differentially expressed genes
      from the collection of independent gene signatures. RESULTS: We identified 33
      eligible gene expression array studies of placental tissue in the 3(rd) trimester
      comprising 30 datasets on mRNA expression and 4 datasets on microRNA expression.
      The pre-eclamptic placental meta-signature consisted of 40 annotated gene
      transcripts and 17 microRNAs. At least half of the mRNA transcripts encode a
      protein that is secreted from the cell and could potentially serve as a
      biomarker. CONCLUSIONS: In addition to well-known and validated genes, we
      identified 14 transcripts not reported previously in relation to pre-eclampsia of
      which the majority is also expressed in the 1(st) trimester placenta, and three
      encode a secreted protein.

PMID- 23874843
TI  - Antiviral activity of glycyrrhizin against hepatitis C virus in vitro.
AB  - Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral
      hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase
      levels. GL is also known to exhibit various biological activities, including anti
      viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be
      clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7
      cells caused a reduction of infectious HCV production using cell culture-produced
      HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV
      pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of
      viral entry and replication steps were not observed. Interestingly, extracellular
      infectivity was decreased, and intracellular infectivity was increased. By
      immunofluorescence and electron microscopic analysis of GL treated cells, HCV
      core antigens and electron-dense particles had accumulated on endoplasmic
      reticulum attached to lipid droplet (LD), respectively, which is thought to act
      as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD
      fraction increased. Taken together, these results suggest that GL inhibits
      release of infectious HCV particles. GL is known to have an inhibitory effect on
      phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also
      decreased HCV release, suggesting that suppression of virus release by GL
      treatment may be due to its inhibitory effect on PLA2G1B. Finally, we
      demonstrated that combination treatment with GL augmented IFN-induced reduction
      of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that
      targets infectious virus particle release. 

PMID- 23874845
TI  - Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune
      hyperactivation.
AB  - Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum
      counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg)
      frequency and suppressive function. Here, we examined the potential role and
      mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose
      gp96 immunization elicited rapid and long-lasting protection of mice against
      concanavalin A (Con A)-and anti-CD137-induced liver injury, as evidenced by
      decreased alanine aminotransaminase (ALT) levels, hepatic necrosis, serum pro
      inflammatory cytokines (IFN-gamma, TNF-alpha, and IL-6), and number of IFN-gamma
      (+) CD4(+) and IFN-gamma (+) CD8(+) T cells in the spleen and liver. In contrast,
      CD4(+)CD25(+)Foxp3(+) Treg frequency and suppressive function were both
      increased, and the protective effect of gp96 could be generated by adoptive
      transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments
      demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive
      function, and up-regulation of Foxp3, IL-10, and TGF-beta1 induced by gp96 was
      dependent on TLR2- and TLR4-mediated NF-kappaB activation. Our work shows that
      activation of Tregs by high-dose gp96 immunization protects against Con A- and
      anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the
      development of a gp96-based anti-immune hyperactivation vaccine against immune
      mediated liver destruction. 

PMID- 23874844
TI  - Increased levels of antigen-bound beta-amyloid autoantibodies in serum and
      cerebrospinal fluid of Alzheimer's disease patients.
AB  - Recent studies have suggested a protective role of physiological beta-amyloid
      autoantibodies (Abeta-autoantibodies) in Alzheimer's disease (AD). However, the
      determination of both free and dissociated Abeta-autoantibodies in serum hitherto
      has yielded inconsistent results regarding their function and possible biomarker
      value. Here we report the application of a new sandwich enzyme-linked
      immunosorbent assay (ELISA) for the determination of antigen-bound Abeta
      autoantibodies (intact Abeta-IgG immune complexes) in serum and cerebrospinal
      fluid (CSF) of a total number of 112 AD patients and age- and gender-matched
      control subjects. Both serum and CSF levels of Abeta-IgG immune complexes were
      found to be significantly higher in AD patients compared to control subjects.
      Moreover, the levels of Abeta-IgG complexes were negatively correlated with the
      cognitive status across the groups, increasing with declining cognitive test
      performance of the subjects. Our results suggest a contribution of IgG-type
      autoantibodies to Abeta clearance in vivo and an increased immune response in AD,
      which may be associated with deficient Abeta-IgG removal. These findings may
      contribute to elucidating the role of Abeta-autoantibodies in AD pathophysiology
      and their potential application in AD diagnosis. 

PMID- 23874846
TI  - Genetic variants in epidermal growth factor receptor pathway genes and risk of
      esophageal squamous cell carcinoma and gastric cancer in a Chinese population.
AB  - The epidermal growth factor receptor (EGFR) signaling pathway regulates cell
      proliferation, differentiation, and survival, and is frequently dysregulated in
      esophageal and gastric cancers. Few studies have comprehensively examined the
      association between germline genetic variants in the EGFR pathway and risk of
      esophageal and gastric cancers. Based on a genome-wide association study in a Han
      Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for
      1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and
      2111 controls. SNP-level analyses were conducted using logistic regression
      models. We applied the resampling-based adaptive rank truncated product approach
      to determine the gene- and pathway-level associations. The EGFR pathway was
      significantly associated with GC risk (P = 2.16*10(-3)). Gene-level analyses
      found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3,
      MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not
      observe a significant pathway-level association (P = 0.72), but gene-level
      analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and
      ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR
      signaling pathway and risk of GC and ESCC. Further studies are warranted to
      validate these associations and to investigate underlying mechanisms. 

PMID- 23874847
TI  - Structural analysis of mitochondrial mutations reveals a role for bigenomic
      protein interactions in human disease.
AB  - Mitochondria are the energy producing organelles of the cell, and mutations
      within their genome can cause numerous and often severe human diseases. At the
      heart of every mitochondrion is a set of five large multi-protein machines
      collectively known as the mitochondrial respiratory chain (MRC). This cellular
      machinery is central to several processes important for maintaining homeostasis
      within cells, including the production of ATP. The MRC is unique due to the
      bigenomic origin of its interacting proteins, which are encoded in the nucleus
      and mitochondria. It is this, in combination with the sheer number of protein
      protein interactions that occur both within and between the MRC complexes, which
      makes the prediction of function and pathological outcome from primary sequence
      mutation data extremely challenging. Here we demonstrate how 3D structural
      analysis can be employed to predict the functional importance of mutations in
      mtDNA protein-coding genes. We mined the MITOMAP database and, utilizing the
      latest structural data, classified mutation sites based on their location within
      the MRC complexes III and IV. Using this approach, four structural classes of
      mutation were identified, including one underexplored class that interferes with
      nuclear-mitochondrial protein interactions. We demonstrate that this class
      currently eludes existing predictive approaches that do not take into account the
      quaternary structural organization inherent within and between the MRC complexes.
      The systematic and detailed structural analysis of disease-associated mutations
      in the mitochondrial Complex III and IV genes significantly enhances the
      predictive power of existing approaches and our understanding of how such
      mutations contribute to various pathologies. Given the general lack of any
      successful therapeutic approaches for disorders of the MRC, these findings may
      inform the development of new diagnostic and prognostic biomarkers, as well as
      new drugs and targets for gene therapy. 

PMID- 23874848
TI  - Resolution doubling in 3D-STORM imaging through improved buffers.
AB  - Super-resolution imaging methods have revolutionized fluorescence microscopy by
      revealing the nanoscale organization of labeled proteins. In particular, single
      molecule methods such as Stochastic Optical Reconstruction Microscopy (STORM)
      provide resolutions down to a few tens of nanometers by exploiting the cycling of
      dyes between fluorescent and non-fluorescent states to obtain a sparse population
      of emitters and precisely localizing them individually. This cycling of dyes is
      commonly induced by adding different chemicals, which are combined to create a
      STORM buffer. Despite their importance, the composition of these buffers has
      scarcely evolved since they were first introduced, fundamentally limiting what
      can be resolved with STORM. By identifying a new chemical suitable for STORM and
      optimizing the buffer composition for Alexa-647, we significantly increased the
      number of photons emitted per cycle by each dye, providing a simple means to
      enhance the resolution of STORM independently of the optical setup used. Using
      this buffer to perform 3D-STORM on biological samples, we obtained images with
      better than 10 nanometer lateral and 30 nanometer axial resolution. 

PMID- 23874849
TI  - Fermentation of xylose causes inefficient metabolic state due to carbon/energy
      starvation and reduced glycolytic flux in recombinant industrial Saccharomyces
      cerevisiae.
AB  - In the present study, comprehensive, quantitative metabolome analysis was carried
      out on the recombinant glucose/xylose-cofermenting S. cerevisiae strain MA-R4
      during fermentation with different carbon sources, including glucose, xylose, or
      glucose/xylose mixtures. Capillary electrophoresis time-of-flight mass
      spectrometry was used to determine the intracellular pools of metabolites from
      the central carbon pathways, energy metabolism pathways, and the levels of twenty
      amino acids. When xylose instead of glucose was metabolized by MA-R4, glycolytic
      metabolites including 3- phosphoglycerate, 2- phosphoglycerate,
      phosphoenolpyruvate, and pyruvate were dramatically reduced, while conversely,
      most pentose phosphate pathway metabolites such as sedoheptulose 7- phosphate and
      ribulose 5-phosphate were greatly increased. These results suggest that the low
      metabolic activity of glycolysis and the pool of pentose phosphate pathway
      intermediates are potential limiting factors in xylose utilization. It was
      further demonstrated that during xylose fermentation, about half of the twenty
      amino acids declined, and the adenylate/guanylate energy charge was impacted due
      to markedly decreased adenosine triphosphate/adenosine monophosphate and
      guanosine triphosphate/guanosine monophosphate ratios, implying that the
      fermentation of xylose leads to an inefficient metabolic state where the
      biosynthetic capabilities and energy balance are severely impaired. In addition,
      fermentation with xylose alone drastically increased the level of citrate in the
      tricarboxylic acid cycle and increased the aromatic amino acids tryptophan and
      tyrosine, strongly supporting the view that carbon starvation was induced.
      Interestingly, fermentation with xylose alone also increased the synthesis of the
      polyamine spermidine and its precursor S-adenosylmethionine. Thus, differences in
      carbon substrates, including glucose and xylose in the fermentation medium,
      strongly influenced the dynamic metabolism of MA-R4. These results provide a
      metabolic explanation for the low ethanol productivity on xylose compared to
      glucose. 

PMID- 23874850
TI  - A paradigm of uphill running.
AB  - The biomechanical management of bioenergetics of runners when running uphill was
      investigated. Several metabolic and mechanical variables have been studied
      simultaneously to spread light on the locomotory strategy operated by humans for
      effective locomotion. The studied variables were: heart rate, heart rate
      variability, oxygen intake and blood lactate, metabolic cost, kinematics, ground
      reaction force and muscular activity. 18 high-level competitive male runners ran
      at 70% VO2max on different uphill slope conditions: 0%, 2% and 7%. Modifications
      were significant in almost all variables studied, and were more pronounced with
      increasing incline. Step frequency/length and ground reaction force are adjusted
      to cope with both the task of uphill progression and the available (limited)
      metabolic power. From 0% to 7% slope, step frequency and ground reaction force
      and metabolic cost increased concurrently by 4%, 12% and 53%, respectively (with
      a 4% step length decrease as well). It is hypothesised that this biomechanical
      management is allowed by an environment-body communication performed by means of
      specific muscular activity. 

PMID- 23874851
TI  - The glucagon-like peptide 1 analogue, exendin-4, attenuates the rewarding
      properties of psychostimulant drugs in mice.
AB  - Glucagon-like peptide 1 (GLP-1) is an incretine hormone that controls
      consummatory behavior and glucose homeostasis. It is released in response to
      nutrient ingestion from the intestine and production in the brain has also been
      identified. Given that GLP-1 receptors are expressed in reward areas, such as the
      nucleus accumbens and ventral tegmental area, and that common mechanisms regulate
      food and drug-induced reward we hypothesize that GLP-1 receptors are involved in
      reward regulation. Herein the effect of the GLP-1 receptor agonist Exendin-4
      (Ex4), on amphetamine- and cocaine-induced activation of the mesolimbic dopamine
      system was investigated in mice. In a series of experiments we show that
      treatment with Ex4, at a dose with no effect per se, reduce amphetamine- as well
      as cocaine-induced locomotor stimulation, accumbal dopamine release as well as
      conditioned place preference in mice. Collectively these data propose a role for
      GLP-1 receptors in regulating drug reward. Moreover, the GLP-1 signaling system
      may be involved in the development of drug dependence since the rewarding effects
      of addictive drugs involves interferences with the mesolimbic dopamine system.
      Given that GLP-1 analogues, such as exenatide and liraglutide, are clinically
      available for treatment of type II diabetes, we propose that these should be
      elucidated as treatments of drug dependence. 

PMID- 23874852
TI  - The dysfunction of CD4(+)CD25(+) regulatory T cells contributes to the abortion
      of mice caused by Toxoplasma gondii excreted-secreted antigens in early
      pregnancy.
AB  - Toxoplasma gondii is an opportunistic intracellular parasite that is highly
      prevalent in human and warm-blooded animals throughout the world, leading to
      potentially severe congenital infections. Although the abortion caused by T.
      gondii is believed to be dependent on the timing of maternal infection during
      pregnancy, the mechanism remains unclear. This study was focused on the effects
      of T. gondii excreted-secreted antigens on pregnant outcomes and CD4(+)CD25(+)
      Foxp3(+) regulatory T cells at different stages of pregnancy. The results showed
      that in mice the frequency and suppressive function of CD4(+)CD25(+) regulatory
      cells were diminished after injection of T. gondii excreted-secreted antigens at
      early and intermediate stages of pregnancy. The abortion caused by T. gondii
      excreted-secreted antigens at early pregnancy could be partly prevented by
      adoptively transferring of CD4(+)CD25(+) cells from the mice injected with T.
      gondii excreted-secreted antigens at late pregnancy, but not from the mice with
      the same treatment at early pregnancy. Furthermore, T. gondii excreted-secreted
      antigens induced apoptosis of CD4(+)CD25(+) regulatory cells of mice in early and
      intermediate stages of pregnancy by down-regulating their Bcl-2 expressions and
      Bcl-2/Bax ratio. This study provides new insights into the mechanism that T.
      gondii infection is the high risk factor for abortion in early pregnancy. 

PMID- 23874853
TI  - Contributory role of five common polymorphisms of RAGE and APE1 genes in lung
      cancer among Han Chinese.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer mortality in China. Given
      the ubiquitous nature of gene-to-gene interaction in lung carcinogenesis, we
      sought to evaluate five common polymorphisms from advanced glycosylation end
      product-specific receptor (RAGE) and apurinic/apyrimidinic endonuclease 1 (APE1)
      genes in association with lung cancer among Han Chinese. METHODS AND RESULTS: 819
      patients with lung cancer and 803 cancer-free controls were recruited from
      Qiqihar city. Genotypes of five examined polymorphisms (RAGE gene: rs1800625,
      rs1800624, rs2070600; APE1 gene: rs1760944, rs1130409) were determined by ligase
      detection reaction method. Data were analyzed by R software and multifactor
      dimensionality reduction (MDR). Hardy-Weinberg equilibrium was satisfied for all
      five polymorphisms. Overall differences in the genotype and allele distributions
      were significant for rs1800625 (Pgenotype<0.0005; Pallele<0.0005), rs2070600
      (Pgenotype = 0.005; Pallele = 0.004) and rs1130409 (Pgenotype = 0.009; Pallele =
      0.004) polymorphisms. Haplotype C-A-A (alleles in order of rs1800625, rs1800624
      and rs2070600) of RAGE gene was overrepresented in patients, and conferred a 2.1
      fold increased risk of lung cancer (95% confidence interval: 1.52-2.91),
      independent of confounding factors. Further application of MDR method to five
      examined polymorphisms identified the overall best interaction model including
      rs2070600 and rs1130409 polymorphisms. This model had a maximal testing accuracy
      of 64.63% and a maximal cross-validation consistency of 9 out of 10 at the
      significant level of 0.006. CONCLUSIONS: Our findings demonstrated a potential
      interactive contribution of RAGE and APE1 genes to the pathogenesis of lung
      cancer among Han Chinese. Further studies are warranted to confirm or refute
      these findings.

PMID- 23874854
TI  - Resistance mutations and CTL epitopes in archived HIV-1 DNA of patients on
      antiviral treatment: toward a new concept of vaccine.
AB  - Eleven patients responding successfully to first-line antiretroviral therapy
      (ART) were investigated for proviral drug resistance mutations (DRMs) in RT by
      ultra-deep pyrosequencing (UDPS). After molecular typing of the class I alleles A
      and B, the CTL epitopes in the Gag, Nef and Pol regions of the provirus were
      sequenced and compared to the reference HXB2 HIV-1 epitopes. They were then
      matched with the HLA alleles with determination of theoretical affinity (TA). For
      3 patients, the results could be compared with an RNA sample of the circulating
      virus at initiation of therapy. Five out of 11 patients exhibited DRMs by UDPS.
      The issue is whether a therapeutic switch is relevant in these patients by taking
      into account the identity of the archived resistance mutations. When the archived
      CTL epitopes were determined on the basis of the HLA alleles, different patterns
      were observed. Some epitopes were identical to those reported for the reference
      with the same TA, while others were mutated with a decrease in TA. In 2 cases, an
      epitope was observed as a combination of subpopulations at entry and was
      retrieved as a single population with lower TA at success. With regard to
      immunological stimulation and given the variability of the archived CTL epitopes,
      we propose a new concept of curative vaccine based on identification of HIV-1 CTL
      epitopes after prior sequencing of proviral DNA and matching with HLA class I
      alleles. 

PMID- 23874855
TI  - Mitochondrial function in human neuroblastoma cells is up-regulated and protected
      by NQO1, a plasma membrane redox enzyme.
AB  - BACKGROUND: Recent findings suggest that NADH-dependent enzymes of the plasma
      membrane redox system (PMRS) play roles in the maintenance of cell bioenergetics
      and oxidative state. Neurons and tumor cells exhibit differential vulnerability
      to oxidative and metabolic stress, with important implications for the
      development of therapeutic interventions that promote either cell survival
      (neurons) or death (cancer cells). METHODS AND FINDINGS: Here we used human
      neuroblastoma cells with low or high levels of the PMRS enzyme NADH-quinone
      oxidoreductase 1 (NQO1) to investigate how the PMRS modulates mitochondrial
      functions and cell survival. Cells with elevated NQO1 levels exhibited higher
      levels of oxygen consumption and ATP production, and lower production of reactive
      oxygen species. Cells overexpressing NQO1 were more resistant to being damaged by
      the mitochondrial toxins rotenone and antimycin A, and exhibited less
      oxidative/nitrative damage and less apoptotic cell death. Cells with basal levels
      of NQO1 resulted in increased oxidative damage to proteins and cellular
      vulnerability to mitochondrial toxins. Thus, mitochondrial functions are enhanced
      and oxidative stress is reduced as a result of elevated PMRS activity, enabling
      cells to maintain redox homeostasis under conditions of metabolic and energetic
      stress. CONCLUSION: These findings suggest that NQO1 is a potential target for
      the development of therapeutic agents for either preventing neuronal degeneration
      or promoting the death of neural tumor cells.

PMID- 23874856
TI  - A targetron system for gene targeting in thermophiles and its application in
      Clostridium thermocellum.
AB  - BACKGROUND: Targetrons are gene targeting vectors derived from mobile group II
      introns. They consist of an autocatalytic intron RNA (a "ribozyme") and an intron
      encoded reverse transcriptase, which use their combined activities to achieve
      highly efficient site-specific DNA integration with readily programmable DNA
      target specificity. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used a mobile group
      II intron from the thermophilic cyanobacterium Thermosynechococcus elongatus to
      construct a thermotargetron for gene targeting in thermophiles. After determining
      its DNA targeting rules by intron mobility assays in Escherichia coli at elevated
      temperatures, we used this thermotargetron in Clostridium thermocellum, a
      thermophile employed in biofuels production, to disrupt six different chromosomal
      genes (cipA, hfat, hyd, ldh, pta, and pyrF). High integration efficiencies (67
      100% without selection) were achieved, enabling detection of disruptants by
      colony PCR screening of a small number of transformants. Because the
      thermotargetron functions at high temperatures that promote DNA melting, it can
      recognize DNA target sequences almost entirely by base pairing of the intron RNA
      with less contribution from the intron-encoded protein than for mesophilic
      targetrons. This feature increases the number of potential targetron-insertion
      sites, while only moderately decreasing DNA target specificity. Phenotypic
      analysis showed that thermotargetron disruption of the genes encoding lactate
      dehydrogenase (ldh; Clo1313_1160) and phosphotransacetylase (pta; Clo1313_1185)
      increased ethanol production in C. thermocellum by decreasing carbon flux toward
      lactate and acetate. CONCLUSIONS/SIGNIFICANCE: Thermotargetron provides a new,
      rapid method for gene targeting and genetic engineering of C. thermocellum, an
      industrially important microbe, and should be readily adaptable for gene
      targeting in other thermophiles.

PMID- 23874858
TI  - SWI/SNF enzymes promote SOX10- mediated activation of myelin gene expression.
AB  - SOX10 is a Sry-related high mobility (HMG)-box transcriptional regulator that
      promotes differentiation of neural crest precursors into Schwann cells,
      oligodendrocytes, and melanocytes. Myelin, formed by Schwann cells in the
      peripheral nervous system, is essential for propagation of nerve impulses.
      SWI/SNF complexes are ATP dependent chromatin remodeling enzymes that are
      critical for cellular differentiation. It was recently demonstrated that the BRG1
      subunit of SWI/SNF complexes activates SOX10 expression and also interacts with
      SOX10 to activate expression of OCT6 and KROX20, two transcriptional regulators
      of Schwann cell differentiation. To determine the requirement for SWI/SNF enzymes
      in the regulation of genes that encode components of myelin, which are downstream
      of these transcriptional regulators, we introduced SOX10 into fibroblasts that
      inducibly express dominant negative versions of the SWI/SNF ATPases, BRM or BRG1.
      Dominant negative BRM and BRG1 have mutations in the ATP binding site and inhibit
      gene activation events that require SWI/SNF function. Ectopic expression of SOX10
      in cells derived from NIH 3T3 fibroblasts led to the activation of the endogenous
      Schwann cell specific gene, myelin protein zero (MPZ) and the gene that encodes
      myelin basic protein (MBP). Thus, SOX10 reprogrammed these cells into myelin gene
      expressing cells. Ectopic expression of KROX20 was not sufficient for activation
      of these myelin genes. However, KROX20 together with SOX10 synergistically
      activated MPZ and MBP expression. Dominant negative BRM and BRG1 abrogated SOX10
      mediated activation of MPZ and MBP and synergistic activation of these genes by
      SOX10 and KROX20. SOX10 was required to recruit BRG1 to the MPZ locus. Similarly,
      in immortalized Schwann cells, BRG1 recruitment to SOX10 binding sites at the MPZ
      locus was dependent on SOX10 and expression of dominant negative BRG1 inhibited
      expression of MPZ and MBP in these cells. Thus, SWI/SNF enzymes cooperate with
      SOX10 to directly activate genes that encode components of peripheral myelin. 

PMID- 23874857
TI  - HIV behind bars: human immunodeficiency virus cluster analysis and drug
      resistance in a reference correctional unit from southern Brazil.
AB  - People deprived of liberty in prisons are at higher risk of infection by the
      human immunodeficiency virus (HIV) due to their increased exposure through
      intravenous drug use, unprotected sexual activity, tattooing in prison and blood
      exposure in fights and rebellions. Yet, the contribution of intramural HIV
      transmission to the epidemic is scarcely known, especially in low- and middle
      income settings. In this study, we surveyed 1,667 inmates incarcerated at
      Presidio Central de Porto Alegre, located in southern Brazil, for HIV infection
      and molecular characterization. The HIV seroprevalence was 6.6% (110/1,667).
      Further analyses were carried out on 40 HIV-seropositive inmates to assess HIV
      transmission clusters and drug resistance within the facility with the use of
      molecular and phylogenetic techniques. The molecular epidemiology of HIV-1
      subtypes observed was similar to the one reported for the general population in
      southern Brazil, with the predominance of HIV-1 subtypes C, B, CRF31_BC and
      unique BC recombinants. In particular, the high rate (24%) of URF_BC found here
      may reflect multiple exposures of the population investigated to HIV infection.
      We failed to find HIV-infected inmates sharing transmission clusters with each
      other. Importantly, the analysis of HIV-1 pol genomic fragments evidenced high
      rates of HIV primary and secondary (acquired) drug resistance and an alarming
      proportion of virologic failure among patients under treatment, unveiling
      suboptimal access to antiretroviral therapy (ARV), low ARV adherence and
      dissemination of drug resistant HIV strains in primary infections. Our results
      call for immediate actions of public authority to implement preventive measures,
      serological screening and, for HIV-seropositive subjects, clinical and treatment
      follow-up in order to control HIV infection and limit the spread of drug
      resistance strains in Brazilian prisons. 

PMID- 23874859
TI  - Phosphatidylinositol 4,5-bisphosphate decreases the concentration of Ca2+,
      phosphatidylserine and diacylglycerol required for protein kinase C alpha to
      reach maximum activity.
AB  - The C2 domain of PKCalpha possesses two different binding sites, one for Ca(2+)
      and phosphatidylserine and a second one that binds PIP2 with very high affinity.
      The enzymatic activity of PKCalpha was studied by activating it with large
      unilamellar lipid vesicles, varying the concentration of Ca(2+) and the contents
      of dioleylglycerol (DOG), phosphatidylinositol 4,5-bisphosphate (PIP2) and
      phosphadidylserine (POPS) in these model membranes. The results showed that PIP2
      increased the Vmax of PKCalpha and, when the PIP2 concentration was 5 mol% of the
      total lipid in the membrane, the addition of 2 mol% of DOG did not increase the
      activity. In addition PIP2 decreases K0.5 of Ca(2+) more than 3-fold, that of DOG
      almost 5-fold and that of POPS by a half. The K0.5 values of PIP2 amounted to
      only 0.11 uM in the presence of DOG and 0.39 in its absence, which is within the
      expected physiological range for the inner monolayer of a mammalian plasma
      membrane. As a consequence, PKCalpha may be expected to operate near its maximum
      capacity even in the absence of a cell signal producing diacylglycerol.
      Nevertheless, we have shown that the presence of DOG may also help, since the
      K0.5 for PIP2 notably decreases in its presence. Taken together, these results
      underline the great importance of PIP2 in the activation of PKCalpha and
      demonstrate that in its presence, the most important cell signal for triggering
      the activity of this enzyme is the increase in the concentration of cytoplasmic
      Ca(2+). 

PMID- 23874860
TI  - Long term SuboxoneTM emotional reactivity as measured by automatic detection in
      speech.
AB  - Addictions to illicit drugs are among the nation's most critical public health
      and societal problems. The current opioid prescription epidemic and the need for
      buprenorphine/naloxone (Suboxone(r); SUBX) as an opioid maintenance substance,
      and its growing street diversion provided impetus to determine affective states
      ("true ground emotionality") in long-term SUBX patients. Toward the goal of
      effective monitoring, we utilized emotion-detection in speech as a measure of
      "true" emotionality in 36 SUBX patients compared to 44 individuals from the
      general population (GP) and 33 members of Alcoholics Anonymous (AA). Other less
      objective studies have investigated emotional reactivity of heroin, methadone and
      opioid abstinent patients. These studies indicate that current opioid users have
      abnormal emotional experience, characterized by heightened response to unpleasant
      stimuli and blunted response to pleasant stimuli. However, this is the first
      study to our knowledge to evaluate "true ground" emotionality in long-term
      buprenorphine/naloxone combination (SuboxoneTM). We found in long-term SUBX
      patients a significantly flat affect (p<0.01), and they had less self-awareness
      of being happy, sad, and anxious compared to both the GP and AA groups. We
      caution definitive interpretation of these seemingly important results until we
      compare the emotional reactivity of an opioid abstinent control using automatic
      detection in speech. These findings encourage continued research strategies in
      SUBX patients to target the specific brain regions responsible for relapse
      prevention of opioid addiction. 

PMID- 23874861
TI  - Objectively measured residential environment and self-reported health: a
      multilevel analysis of UK census data.
AB  - Little is known about the association between health and the quality of the
      residential environment. What is known is often based on subjective assessments
      of the environment rather than on measurements by independent observers. The aim
      of this study, therefore, was to determine the association between self-reported
      general health and an objectively assessed measure of the residential
      environment. We studied over 30,000 residents aged 18 or over living in 777
      neighbourhoods in south Wales. Built environment quality was measured by
      independent observers using a validated tool, the Residential Environment
      Assessment Tool (REAT), at unit postcode level. UK Census data on each resident,
      which included responses to a question which assessed self-reported general
      health, was linked to the REAT score. The Census data also contained detailed
      information on socio-economic and demographic characteristics of all respondents
      and was also linked to the Welsh Index of Multiple Deprivation. After adjusting
      for both the individual characteristics and area deprivation, respondents in the
      areas of poorest neighbourhood quality were more likely to report poor health
      compared to those living in areas of highest quality (OR 1.36, 95% confidence
      interval 1.22-1.49). The particular neighbourhood characteristics associated with
      poor health were physical incivilities and measures of how well the residents
      maintained their properties. Measures of green space were not associated with
      self-reported health. This is the first full population study to examine such
      associations and the results demonstrate the importance for health of the quality
      of the neighbourhood area in which people live and particularly the way in which
      residents behave towards their own and their neighbours' property. A better
      understanding of causal pathways that allows the development of interventions to
      improve neighbourhood quality would offer significant potential health gains. 

PMID- 23874862
TI  - Pixels as ROIs (PAR): a less-biased and statistically powerful approach for
      gleaning functional information from image stacks.
AB  - Especially in the last decade or so, there have been dramatic advances in
      fluorescence-based imaging methods designed to measure a multitude of functions
      in living cells. Despite this, many of the methods used to analyze the resulting
      images are limited. Perhaps the most common mode of analysis is the choice of
      regions of interest (ROIs), followed by quantification of the signal contained
      therein in comparison with another "control" ROI. While this method has several
      advantages, such as flexibility and capitalization on the power of human visual
      recognition capabilities, it has the drawbacks of potential subjectivity and lack
      of precisely defined criteria for ROI selection. This can lead to analyses which
      are less precise or accurate than the data might allow for, and generally a
      regrettable loss of information. Herein, we explore the possibility of abandoning
      the use of conventional ROIs, and instead propose treating individual pixels as
      ROIs, such that all information can be extracted systematically with the various
      statistical cutoffs we discuss. As a test case for this approach, we monitored
      intracellular pH in cells transfected with the chloride/bicarbonate transporter
      slc26a3 using the ratiometric dye SNARF-5F under various conditions. We performed
      a parallel analysis using two different levels of stringency in conventional ROI
      analysis as well as the pixels-as-ROIs (PAR) approach, and found that pH
      differences between control and transfected cells were accentuated by ~50-100% by
      using the PAR approach. We therefore consider this approach worthy of adoption,
      especially in cases in which higher accuracy and precision are required. 

PMID- 23874863
TI  - Transgenic overexpression of ephrin b1 in bone cells promotes bone formation and
      an anabolic response to mechanical loading in mice.
AB  - To test if ephrin B1 overexpression enhances bone mass, we generated transgenic
      mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1
      promoter (Col3.6-Tg (efnb1) ). Col3.6-Tg (efnb1) mice express 6-, 12- and 14-fold
      greater levels of full-length ephrin B1 protein in bone marrow stromal cells,
      calvarial osteoblasts, and osteoclasts, respectively. The long bones of both
      genders of Col3.6-Tg (efnb1) mice have increased trabecular bone volume,
      trabecular number, and trabecular thickness and decreased trabecular separation.
      Enhanced bone formation and decreased bone resorption contributed to this
      increase in trabecular bone mass in Col3.6-Tg (efnb1) mice. Consistent with these
      findings, our in vitro studies showed that overexpression of ephrin B1 increased
      osteoblast differentiation and mineralization, osterix and collagen 1A1
      expression in bone marrow stromal cells. Interaction of ephrin B1 with soluble
      clustered EphB2-Fc decreased osteoclast precursor differentiation into
      multinucleated cells. Furthermore, we demonstrated that the mechanical loading
      induced increase in EphB2 expression and newly formed bone were significantly
      greater in the Col3.6-Tg (efnb1) mice than in WT littermate controls. Our
      findings that overexpression of ephrin B1 in bone cells enhances bone mass and
      promotes a skeletal anabolic response to mechanical loading suggest that
      manipulation of ephrin B1 actions in bone may provide a means to sensitize the
      skeleton to mechanical strain to stimulate new bone formation. 

PMID- 23874864
TI  - Partially silencing brain toll-like receptor 4 prevents in part left ventricular
      remodeling with sympathoinhibition in rats with myocardial infarction-induced
      heart failure.
AB  - BACKGROUND: Left ventricular (LV) remodeling and activation of sympathetic
      nervous system (SNS) are cardinal features of heart failure. We previously
      demonstrated that enhanced central sympathetic outflow is associated with brain
      toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1
      receptor in mice with myocardial infarction (MI)-induced heart failure. The
      purpose of the present study was to examine whether silencing brain TLR4 could
      prevent LV remodeling with sympathoinhibition in MI-induced heart failure.
      METHODOLOGY/PRINCIPAL FINDINGS: MI-induced heart failure model rats were created
      by ligation of left coronary artery. The expression level of TLR4 in brainstem
      was significantly higher in MI-induced heart failure treated with
      intracerebroventricular (ICV) injection of hGAPDH-SiRNA than in sham. TLR4 in
      brainstem was significantly lower in MI-induced heart failure treated with ICV
      injection of TLR4-SiRNA than in that treated with ICV injection of hGAPDH-SiRNA.
      Lung weight, urinary norepinephrine excretion, and LV end-diastolic pressure were
      significantly lower and LV dimension was significantly smaller in MI-induced
      heart failure treated with TLR4-SiRNA than in that treated with hGAPDH-SiRNA for
      2 weeks. CONCLUSIONS: Partially silencing brain TLR4 by ICV injection of TLR4
      SiRNA for 2 weeks could in part prevent LV remodeling with sympathoinhibition in
      rats with MI-induced heart failure. Brain TLR4 has a potential to be a target of
      the treatment for MI-induced heart failure.

PMID- 23874865
TI  - Noisy galvanic vestibular stimulation modulates the amplitude of EEG synchrony
      patterns.
AB  - Noisy galvanic vestibular stimulation has been associated with numerous cognitive
      and behavioural effects, such as enhancement of visual memory in healthy
      individuals, improvement of visual deficits in stroke patients, as well as
      possibly improvement of motor function in Parkinson's disease; yet, the mechanism
      of action is unclear. Since Parkinson's and other neuropsychiatric diseases are
      characterized by maladaptive dynamics of brain rhythms, we investigated whether
      noisy galvanic vestibular stimulation was associated with measurable changes in
      EEG oscillatory rhythms within theta (4-7.5 Hz), low alpha (8-10 Hz), high alpha
      (10.5-12 Hz), beta (13-30 Hz) and gamma (31-50 Hz) bands. We recorded the EEG
      while simultaneously delivering noisy bilateral, bipolar stimulation at varying
      intensities of imperceptible currents - at 10, 26, 42, 58, 74 and 90% of sensory
      threshold - to ten neurologically healthy subjects. Using standard spectral
      analysis, we investigated the transient aftereffects of noisy stimulation on
      rhythms. Subsequently, using robust artifact rejection techniques and the Least
      Absolute Shrinkage Selection Operator regression and cross-validation, we
      assessed the combinations of channels and power spectral features within each EEG
      frequency band that were linearly related with stimulus intensity. We show that
      noisy galvanic vestibular stimulation predominantly leads to a mild suppression
      of gamma power in lateral regions immediately after stimulation, followed by
      delayed increase in beta and gamma power in frontal regions approximately 20-25 s
      after stimulation ceased. Ongoing changes in the power of each oscillatory band
      throughout frontal, central/parietal, occipital and bilateral electrodes
      predicted the intensity of galvanic vestibular stimulation in a stimulus
      dependent manner, demonstrating linear effects of stimulation on brain rhythms.
      We propose that modulation of neural oscillations is a potential mechanism for
      the previously-described cognitive and motor effects of vestibular stimulation,
      and noisy galvanic vestibular stimulation may provide an additional non-invasive
      means for neuromodulation of functional brain networks. 

PMID- 23874866
TI  - Extracellular ATP released by osteoblasts is a key local inhibitor of bone
      mineralisation.
AB  - Previous studies have shown that exogenous ATP (>1 uM) prevents bone formation in
      vitro by blocking mineralisation of the collagenous matrix. This effect is
      thought to be mediated via both P2 receptor-dependent pathways and a receptor
      independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor
      pyrophosphate, PP(i)). Osteoblasts are also known to release ATP constitutively.
      To determine whether this endogenous ATP might exert significant biological
      effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5 U/ml
      apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2 P(i)). Addition of
      0.5 U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1%
      of control levels within 2 minutes; continuous exposure to apyrase maintained
      this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of
      culture caused small decreases (<=25%) in osteoblast number, suggesting a role
      for endogenous ATP in stimulating cell proliferation. Continuous apyrase
      treatment for 14 days (>=0.5 U/ml) increased mineralisation of bone nodules by up
      to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were
      cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with
      P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP)
      activity by up to 60%, whilst increasing the activity of the PP(i)-generating
      ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both
      collagen production and adipocyte formation were unaffected. These data suggest
      that nucleotides released by osteoblasts in bone could act locally, via multiple
      mechanisms, to limit mineralisation.

PMID- 23874867
TI  - Degradation of MUC7 and MUC5B in human saliva.
AB  - BACKGROUND: Two types of mucins, MUC7 and MUC5B constitute the major salivary
      glycoproteins, however their metabolic turnover has not been elucidated in detail
      to date. This study was conducted to examine turnover of MUC7 and MUC5B in
      saliva, by focusing on the relationship between their deglycosylation and
      proteolysis. METHODOLOGY/PRINCIPAL FINDINGS: Whole saliva samples were collected
      from healthy individuals and incubated at 37 degrees C in the presence of various
      protease inhibitors, sialidase, or a sialidase inhibitor. General degradation
      patterns of salivary proteins and glycoproteins were examined by SDS
      polyacrylamide-gel-electrophoresis. Furthermore, changes of molecular sizes of
      MUC7 and MUC5B were examined by Western blot analysis. A protein band was
      identified as MUC7 by Western blot analysis using an antibody recognizing an N
      terminal epitope. The MUC7 signal disappeared rapidly after 20-minutes of
      incubation. In contrast, the band of MUC7 stained for its carbohydrate components
      remained visible near its original position for a longer time indicating that the
      rapid loss of Western blot signal was due to the specific removal of the N
      termimal epitope. Pretreatment of saliva with sialidase facilitated MUC7 protein
      degradation when compared with samples without treatment. Furthermore, addition
      of sialidase inhibitor to saliva prevented proteolysis of N-terminus of MUC7,
      suggesting that the desialylation is a prerequisite for the degradation of the N
      terminal region of MUC7. The protein band corresponding to MUC5B detected in both
      Western blotting and glycoprotein staining showed little sign of significant
      degradation upon incubation in saliva up to 9 hours. CONCLUSIONS/SIGNIFICANCE:
      MUC7 was highly susceptible to specific proteolysis in saliva, though major part
      of MUC5B was more resistant to degradation. The N-terminal region of MUC7,
      particularly sensitive to proteolytic degradation, has also been proposed to have
      distinct biological function such as antibacterial activities. Quick removal of
      this region may have biologically important implication.

PMID- 23874868
TI  - Self-reported adherence to medications in a pediatric renal clinic: psychological
      aspects.
AB  - BACKGROUND: Chronically ill children and adolescents comprise a vulnerable
      population that requires specific considerations in order to positively impact
      their treatment outcome. Pediatric renal patients can be non-compliant and also
      forgetful in taking their medications. OBJECTIVE: The objectives of the study
      were to (a) assess medication adherence and (b) to identify emotionality and
      variables that influence non-adherence by use of "The Child & Adolescent
      Adherence to Medication Questionnaire" (CAAMQ), which was constructed at Texas
      Tech University Health Sciences Center. METHODS: Pediatric renal patients from 10
      to 21 years-of-age, taking three or more medications, for longer than a three
      month period, were eligible to complete the CAAMQ. RESULTS: Thirty-four patients
      participated in the study. Many of the respondents had problems remembering to
      take their medications on weekends (P = 0.021). The majority of the patients
      stated that they were not bothered about having to take their medications
      (70.6%); and that taking pills did not interfere with their daily activities
      (85.3%). Open-ended questions in the CAAMQ identified patients' feelings of
      sadness, distress, and the importance of strong family support systems. The study
      participants reported that they preferred to take their medications at school, in
      the nurses' office or in a place where privacy was assured. The results indicated
      that Prednisone was the most disliked of all of the medications. Female patients
      were more reactive and secretive than males regarding peers knowing about their
      disease and medication schedules (P<0.017). CONCLUSIONS: Non-adherence in
      pediatric patients is a complex and serious problem, which ultimately affects the
      patients' health. Privacy and daily routine were found to impact the patients'
      adherence to medications. Creative and individualized reminders for teenagers
      need to be developed and validated. Further studies that take into consideration
      developmental and motivational factors may help researchers identify modifiable
      psychosocial predictors that will lead to improved medication adherence.

PMID- 23874870
TI  - Parent-reported otorrhea in children with tympanostomy tubes: incidence and
      predictors.
AB  - PURPOSE: Although common in children with tympanostomy tubes, the current
      incidence of tympanostomy tube otorrhea (TTO) is uncertain. TTO is generally a
      sign of otitis media, when middle ear fluid drains through the tube. Predictors
      for otitis media are therefore suggested to have predictive value for the
      occurrence of TTO. OBJECTIVE: To determine the incidence of TTO and its
      predictors. METHODS: We performed a cohort study, using a parental web-based
      questionnaire to retrospectively collect data on TTO episodes and its potential
      predictors from children younger than 10 years of age with tympanostomy tubes.
      RESULTS: Of the 1,184 children included in analyses (total duration of time since
      tube placement was 768 person years with a mean of 7.8 months per child), 616
      children (52%) experienced one or more episodes of TTO. 137 children (12%) had
      TTO within the calendar month of tube placement. 597 (50%) children had one or
      more acute TTO episodes (duration <4 weeks) and 46 children (4%) one or more
      chronic TTO episodes (duration >=4 weeks). 146 children (12%) experienced
      recurrent TTO episodes. Accounting for time since tube placement, 67% of children
      developed one or more TTO episodes in the year following tube placement. Young
      age, recurrent acute otitis media being the indication for tube placement, a
      recent history of recurrent upper respiratory tract infections and the presence
      of older siblings were independently associated with the future occurrence of
      TTO, and can therefore be seen as predictors for TTO. CONCLUSIONS: Our survey
      confirms that otorrhea is a common sequela in children with tympanostomy tubes,
      which occurrence can be predicted by age, medical history and presence of older
      siblings.

PMID- 23874869
TI  - The efficiency of homologous recombination and non-homologous end joining systems
      in repairing double-strand breaks during cell cycle progression.
AB  - This study investigated the efficiency of Non-Homologous End Joining (NHEJ) and
      Homologous Recombination (HR) repair systems in rejoining DNA double-strand
      breaks (DSB) induced in CCD-34Lu cells by different gamma-ray doses. The kinetics
      of DNA repair was assessed by analyzing the fluorescence decrease of gamma-H2AX
      foci measured by SOID (Sum Of Integrated Density) parameter and counting foci
      number in the time-interval 0.5-24 hours after irradiation. Comparison of the two
      methods showed that the SOID parameter was useful in determining the amount and
      the persistence of DNA damage signal after exposure to high or low doses of
      ionizing radiation. The efficiency of DSB rejoining during the cell cycle was
      assessed by distinguishing G1, S, and G2 phase cells on the basis of nuclear
      fluorescence of the CENP-F protein. Six hours after irradiation, gamma-H2AX foci
      resolution was higher in G2 compared to G1 cells in which both NHEJ and HR can
      cooperate. The rejoining of gamma-H2AX foci in G2 phase cells was, moreover,
      decreased by RI-1, the chemical inhibitor of HR, demonstrating that homologous
      recombination is at work early after irradiation. The relevance of HR in DSB
      repair was assessed in DNA-PK-deficient M059J cells and in CCD-34Lu treated with
      the DNA-PKcs inhibitor, NU7026. In both conditions, the kinetics of gamma-H2AX
      demonstrated that DSBs repair was markedly affected when NHEJ was absent or
      impaired, even in G2 phase cells in which HR should be at work. The recruitment
      of RAD51 at DSB sites was, moreover, delayed in M059J and in NU7026 treated-CCD
      34Lu, with respect to DNA-PKcs proficient cells and continued for 24 hours
      despite the decrease in DNA repair. The impairment of NHEJ affected the
      efficiency of the HR system and significantly decreased cell survival after
      ionizing radiation, confirming that DSB rejoining is strictly dependent on the
      integrity of the NHEJ repair system. 

PMID- 23874871
TI  - Climate control on tree growth at the upper and lower treelines: a case study in
      the qilian mountains, tibetan plateau.
AB  - It is generally hypothesized that tree growth at the upper treeline is normally
      controlled by temperature while that at the lower treeline is precipitation
      limited. However, uniform patterns of inter-annual ring-width variations along
      altitudinal gradients are also observed in some situations. How changing
      elevation influences tree growth in the cold and arid Qilian Mountains, on the
      northeastern Tibetan Plateau, is of considerable interest because of the
      sensitivity of the region's local climate to different atmospheric circulation
      patterns. Here, a network of four Qilian juniper (Sabina przewalskii Kom.) ring
      width chronologies was developed from trees distributed on a typical mountain
      slope at elevations ranging from 3000 to 3520 m above sea level (a.s.l.). The
      statistical characteristics of the four tree-ring chronologies show no
      significant correlation with increasing elevation. All the sampled tree growth
      was controlled by a common climatic signal (local precipitation) across the
      investigated altitudinal gradient (520 m). During the common reliable period,
      covering the past 450 years, the four chronologies have exhibited coherent growth
      patterns in both the high- and low-frequency domains. These results contradict
      the notion of contrasting climate growth controls at higher and lower elevations,
      and specifically the assumption that inter-annual tree-growth variability is
      controlled by temperature at the upper treeline. It should be stressed that these
      results relate to the relatively arid conditions at the sampling sites in the
      Qilian Mountains. 

PMID- 23874872
TI  - The cognitive building blocks of emotion regulation: ability to update working
      memory moderates the efficacy of rumination and reappraisal on emotion.
AB  - The ability to regulate emotions is a critical component of healthy emotional
      functioning. Therefore, it is important to determine factors that contribute to
      the efficacy of emotion regulation. The present article examined whether the
      ability to update emotional information in working memory is a predictor of the
      efficacy of rumination and reappraisal on affective experience both at the trait
      level (Study 1) and in daily life (Study 2). In both studies, results revealed
      that the relationship between use of reappraisal and high arousal negative
      emotions was moderated by updating ability. Specifically, use of reappraisal was
      associated with decreased high arousal negative emotions for participants with
      high updating ability, while no significant relationship was found for those with
      low updating ability. In addition, both studies also revealed that the
      relationship between rumination and high arousal negative emotions was moderated
      by updating ability. In general, use of rumination was associated with elevated
      high arousal negative emotions. However, this relationship was blunted for
      participants with high updating ability. That is, use of rumination was
      associated with less elevated high arousal negative emotions for participants
      with high updating ability. These results identify the ability to update
      emotional information in working memory as a crucial process modulating the
      efficacy of emotion regulation efforts. 

PMID- 23874873
TI  - Cancer risk in children and adolescents with birth defects: a population-based
      cohort study.
AB  - OBJECTIVE: Birth defects are an increasing health priority worldwide, and the
      subject of a major 2010 World Health Assembly Resolution. Excess cancer risk may
      be an added burden in this vulnerable group of children, but studies to date have
      provided inconsistent findings. This study assessed the risk for cancer in
      children and young adolescents with major birth defects. METHODS AND FINDINGS:
      This retrospective, statewide, population-based, cohort study was conducted in
      three US states (Utah, Arizona, Iowa). A cohort of 44,151 children and young
      adolescents (0 through 14 years of age) with selected major, non-chromosomal
      birth defects or chromosomal anomalies was compared to a reference cohort of
      147,940 children without birth defects randomly sampled from each state's births
      and frequency matched by year of birth. The primary outcome was rate of cancer
      prior to age 15 years, by type of cancer and type of birth defect. The incidence
      of cancer was increased 2.9-fold (95% CI, 2.3 to 3.7) in children with birth
      defects (123 cases of cancer) compared to the reference cohort; the incidence
      rates were 33.8 and 11.7 per 100,000 person-years, respectively. However, the
      excess risk varied markedly by type of birth defect. Increased risks were seen in
      children with microcephaly, cleft palate, and selected eye, cardiac, and renal
      defects. Cancer risk was not increased with many common birth defects, including
      hypospadias, cleft lip with or without cleft palate, or hydrocephalus.
      CONCLUSION: Children with some structural, non-chromosomal birth defects, but not
      others, have a moderately increased risk for childhood cancer. Information on
      such selective risk can promote more effective clinical evaluation, counseling,
      and research.

PMID- 23874874
TI  - Runx transcription factors repress human and murine c-Myc expression in a DNA
      binding and C-terminally dependent manner.
AB  - The transcription factors Runx1 and c-Myc have individually been shown to
      regulate important gene targets as well as to collaborate in oncogenesis.
      However, it is unknown whether there is a regulatory relationship between the two
      genes. In this study, we investigated the transcriptional regulation of
      endogenous c-Myc by Runx1 in the human T cell line Jurkat and murine primary
      hematopoietic cells. Endogenous Runx1 binds to multiple sites in the c-Myc locus
      upstream of the c-Myc transcriptional start site. Cells transduced with a C
      terminally truncated Runx1 (Runx1.d190), which lacks important cofactor
      interaction sites and can block C-terminal-dependent functions of all Runx
      transcription factors, showed increased transcription of c-Myc. In order to
      monitor c-Myc expression in response to early and transiently-acting Runx1.d190,
      we generated a cell membrane-permeable TAT-Runx1.d190 fusion protein. Murine
      splenocytes treated with TAT-Runx1.d190 showed an increase in the transcription
      of c-Myc within 2 hours, peaking at 4 hours post-treatment and declining
      thereafter. This effect is dependent on the ability of Runx1.d190 to bind to DNA.
      The increase in c-Myc transcripts is correlated with increased c-Myc protein
      levels. Collectively, these data show that Runx1 directly regulates c-Myc
      transcription in a C-terminal- and DNA-binding-dependent manner. 

PMID- 23874875
TI  - Identification of a lifespan extending mutation in the Schizosaccharomyces pombe
      cyclin gene clg1+ by direct selection of long-lived mutants.
AB  - Model organisms such as budding yeast, worms and flies have proven instrumental
      in the discovery of genetic determinants of aging, and the fission yeast
      Schizosaccharomyces pombe is a promising new system for these studies. We devised
      an approach to directly select for long-lived S. pombe mutants from a random DNA
      insertion library. Each insertion mutation bears a unique sequence tag called a
      bar code that allows one to determine the proportion of an individual mutant in a
      culture containing thousands of different mutants. Aging these mutants in culture
      allowed identification of a long-lived mutant bearing an insertion mutation in
      the cyclin gene clg1(+). Clg1p, like Pas1p, physically associates with the cyclin
      dependent kinase Pef1p. We identified a third Pef1p cyclin, Psl1p, and found that
      only loss of Clg1p or Pef1p extended lifespan. Genetic and co-immunoprecipitation
      results indicate that Pef1p controls lifespan through the downstream protein
      kinase Cek1p. While Pef1p is conserved as Pho85p in Saccharomyces cerevisiae, and
      as cdk5 in humans, genome-wide searches for lifespan regulators in S. cerevisiae
      have never identified Pho85p. Thus, the S. pombe system can be used to identify
      novel, evolutionarily conserved lifespan extending mutations, and our results
      suggest a potential role for mammalian cdk5 as a lifespan regulator.

PMID- 23874876
TI  - Comparison of arterial spin labeling and dynamic susceptibility contrast
      perfusion MRI in patients with acute stroke.
AB  - BACKGROUND: The aim of this study was to evaluate whether arterial spin labeling
      (ASL) perfusion magnetic resonance imaging (MRI) can reliably quantify perfusion
      deficit as compared to dynamic susceptibility contrast (DSC) perfusion MRI.
      METHODS: Thirty-nine patients with acute ischemic stroke in the anterior
      circulation territory were recruited. All underwent ASL and DSC MRI perfusion
      scans within 30 hours after stroke onset and 31 patients underwent follow-up MRI
      scans. ASL cerebral blood flow (CBF) and DSC time to maximum (T(max)) maps were
      used to calculate the perfusion defects. The ASL CBF lesion volume was compared
      to the DSC Tmax lesion volume by Pearson's correlation coefficient and likewise
      the ASL CBF and DSC T(max) lesion volumes were compared to the final infarct
      sizes respectively. A repeated measures analysis of variance and least
      significant difference post hoc test was used to compare the mean lesion volumes
      among ASL CBF, DSC T(max) >4-6 s and final infarct. RESULTS: Mean patient age was
      72.6 years. The average time from stroke onset to MRI was 13.9 hours. The ASL
      lesion volume showed significant correlation with the DSC lesion volume for
      T(max) >4, 5 and 6 s (r = 0.81, 0.82 and 0.80; p<0.001). However, the mean lesion
      volume of ASL (50.1 ml) was significantly larger than those for T(max) >5 s (29.2
      ml, p<0.01) and T(max) >6 s (21.8 ml, p<0.001), while the mean lesion volumes for
      T(max) >5 or 6 s were close to mean final infarct size. CONCLUSION: Quantitative
      measurement of ASL perfusion is well correlated with DSC perfusion. However, ASL
      perfusion may overestimate the perfusion defects and therefore further refinement
      of the true penumbra threshold and improved ASL technique are necessary before
      applying ASL in therapeutic trials.

PMID- 23874877
TI  - Spatial variation in population structure and its relation to movement and the
      potential for dispersal in a model intertidal invertebrate.
AB  - Dispersal, the movement of an individual away from its natal or breeding ground,
      has been studied extensively in birds and mammals to understand the costs and
      benefits of movement behavior. Whether or not invertebrates disperse in response
      to such attributes as habitat quality or density of conspecifics remains
      uncertain, due in part to the difficulties in marking and recapturing
      invertebrates. In the upper Bay of Fundy, Canada, the intertidal amphipod
      Corophium volutator swims at night around the new or full moon. Furthermore, this
      species is regionally widespread across a large spatial scale with site-to-site
      variation in population structure. Such variation provides a backdrop against
      which biological determinants of dispersal can be investigated. We conducted a
      large-scale study at nine mudflats, and used swimmer density, sampled using
      stationary plankton nets, as a proxy for dispersing individuals. We also sampled
      mud residents using sediment cores over 3 sampling rounds (20-28 June, 10-17
      July, 2-11 August 2010). Density of swimmers was most variable at the largest
      spatial scales, indicating important population-level variation. The smallest
      juveniles and large juveniles or small adults (particularly females) were
      consistently overrepresented as swimmers. Small juveniles swam at most times and
      locations, whereas swimming of young females decreased with increasing mud
      presence of young males, and swimming of large juveniles decreased with
      increasing mud presence of adults. Swimming in most stages increased with density
      of mud residents; however, proportionally less swimming occurred as total mud
      resident density increased. We suggest small juveniles move in search of C.
      volutator aggregations which possibly act as a proxy for better habitat. We also
      suggest large juveniles and small adults move if potential mates are limiting.
      Future studies can use sampling designs over large spatial scales with varying
      population structure to help understand the behavioral ecology of movement, and
      dispersal in invertebrate taxa. 

PMID- 23874878
TI  - Injury-dependent retention of intraportally administered mesenchymal stromal
      cells following partial hepatectomy of steatotic liver does not lead to improved
      liver recovery.
AB  - The aim of this study was to evaluate the effect of bone marrow-derived
      mesenchymal stromal cell (BM-MSC) administration on liver function following
      partial hepatectomy (PHx) of methionine/choline-deficient (MCD) diet induced
      steatotic livers in rodents. Here we identified and validated serum
      cholinesterase (CHE) and triglyceride (TG) levels as non-invasive markers to
      longitudinally monitor rat liver function. Using in vivo bioluminescence imaging,
      retention of BM-MSC in the liver was observed following intraportal
      administration, but not after intravenous administration. Therefore, BM-MSC were
      intraportally delivered to investigate the effect on liver recovery and/or
      regeneration after PHx. However, despite recovery to normal body weight, liver
      weight and NAS score, both serum CHE and TG levels of non-treated and cell
      treated rats with PHx after MCD diet remained significantly lower as compared to
      those of control rats. Importantly, serum CHE levels, but not TG levels, of cell
      treated rats remained significantly lower as compared to those of non-treated
      rats, thereby warranting that certain caution should be considered for future
      clinical application of IP BM-MSC administration in order to promote liver
      regeneration and/or function. 

PMID- 23874879
TI  - Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas.
AB  - BACKGROUND: Her2 expression and amplification occurs in a significant subset of
      gastro-esophageal carcinomas. Her2 is a client protein of molecular chaperones,
      e.g. heat shock protein (HSP) 90, rendering targeted therapies against Her2/HSP90
      an interesting approach. This study aimed to investigate the role and
      relationship of Her2 and HSP90 in gastric and gastro-esophageal adenocarcinomas.
      MATERIAL AND METHODS: Immunohistochemical determination of HSP90 and Her2
      expression was performed on 347 primary resected tumors. Her2 amplification was
      additionally determined by fluorescence in situ hybridization for all cases.
      Expression and amplification results were correlated with pathologic parameters
      (UICC pTNM category, tumor grading) and survival. RESULTS: Elevated Her2 copy
      numbers were observed in 87 tumors, 21 of them showing amplification. 174 tumors
      showed Her2 immunoreactivity/expression. HSP 90 immunoreactivity was found in 125
      tumors. There was no difference between gastric carcinomas and carcinomas of the
      gastroesophageal junction regarding Her2 or HSP90. Both high HSP90 and Her2
      expression/amplification were associated with earlier tumor stages (p<0.01),
      absence of lymph node metastases (p<0.02) and Laurens intestinal type (p<0.001).
      HSP90 correlated with Her2 expression and amplification (p<0.001 each).
      Expressions of HSP90 and Her2, but not Her2 amplification were associated with
      better prognosis (p=0.02; p=0.004; p=0.802). Moreover, Her2 expression was an
      independent prognostic factor for overall survival in the subgroup of gastric
      carcinoma patients (p=0.014) besides pT category, pN category and distant
      metastases. CONCLUSION: Her2 expression and gene amplification occurred in a
      significant subset of cases. Our results suggest a favorable prognostic impact of
      Her2 expression. This warrants further investigations regarding the significance
      of Her2 non-amplified tumors showing Her2 immunoreactivity and the definition of
      Her2 status in gastric cancers. Moreover, the correlation of Her2 expression with
      the expression of Her2 chaperoning HSP90 may indicate a synergistic regulation.
      Targeting HSP90 with or without Her2 may offer additional therapeutic options for
      gastric carcinoma treatment.

PMID- 23874880
TI  - Targeting mTOR to overcome epidermal growth factor receptor tyrosine kinase
      inhibitor resistance in non-small cell lung cancer cells.
AB  - AIMS: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)
      have shown dramatic clinical benefits in advanced non-small cell lung cancer
      (NSCLC); however, resistance remains a serious problem in clinical practice. The
      present study analyzed mTOR-associated signaling-pathway differences between the
      EGFR TKI-sensitive and -resistant NSCLC cell lines and investigated the
      feasibility of targeting mTOR with specific mTOR inhibitor in EGFR TKI resistant
      NSCLC cells. METHODS: We selected four different types of EGFR TKI-sensitive and 
      resistant NSCLC cells: PC9, PC9GR, H1650 and H1975 cells as models to detect mTOR
      associated signaling-pathway differences by western blot and Immunoprecipitation
      and evaluated the antiproliferative effect and cell cycle arrest of ku-0063794 by
      MTT method and flow cytometry. RESULTS: In the present study, we observed that
      mTORC2-associated Akt ser473-FOXO1 signaling pathway in a basal state was highly
      activated in resistant cells. In vitro mTORC1 and mTORC2 kinase activities assays
      showed that EGFR TKI-resistant NSCLC cell lines had higher mTORC2 kinase
      activity, whereas sensitive cells had higher mTORC1 kinase activity in the basal
      state. The ATP-competitive mTOR inhibitor ku-0063794 showed dramatic
      antiproliferative effects and G1-cell cycle arrest in both sensitive and
      resistant cells. Ku-0063794 at the IC50 concentration effectively inhibited both
      mTOR and p70S6K phosphorylation levels; the latter is an mTORC1 substrate and did
      not upregulate Akt ser473 phosphorylation which would be induced by rapamycin and
      resulted in partial inhibition of FOXO1 phosphorylation. We also observed that
      EGFR TKI-sensitive and -resistant clinical NSCLC tumor specimens had higher total
      and phosphorylated p70S6K expression levels. CONCLUSION: Our results indicate
      mTORC2-associated signaling-pathway was hyperactivated in EGFR TKI-resistant
      cells and targeting mTOR with specific mTOR inhibitors is likely a good strategy
      for patients with EGFR mutant NSCLC who develop EGFR TKI resistance; the
      potential specific roles of mTORC2 in EGFR TKI-resistant NSCLC cells were still
      unknown and should be further investigated.

PMID- 23874881
TI  - Sex-differences of face coding: evidence from larger right hemispheric M170 in
      men and dipole source modelling.
AB  - The processing of faces relies on a specialized neural system comprising
      bilateral cortical structures with a dominance of the right hemisphere. However,
      due to inconsistencies of earlier findings as well as more recent results such
      functional lateralization has become a topic of discussion. In particular,
      studies employing behavioural tasks and electrophysiological methods indicate a
      dominance of the right hemisphere during face perception only in men whereas
      women exhibit symmetric and bilateral face processing. The aim of this study was
      to further investigate such sex differences in hemispheric processing of
      personally familiar and opposite-sex faces using whole-head
      magnetoencephalography (MEG). We found a right-lateralized M170-component in
      occipito-temporal sensor clusters in men as opposed to a bilateral response in
      women. Furthermore, the same pattern was obtained in performing dipole
      localization and determining dipole strength in the M170-timewindow. These
      results suggest asymmetric involvement of face-responsive neural structures in
      men and allow to ascribe this asymmetry to the fusiform gyrus. This specifies
      findings from previous investigations employing event-related potentials (ERP)
      and LORETA reconstruction methods yielding rather extended bilateral activations
      showing left asymmetry in women and right lateralization in men. We discuss our
      finding of an asymmetric fusiform activation pattern in men in terms of holistic
      face processing during face evaluation and sex differences with regard to visual
      strategies in general and interest for opposite faces in special. Taken together
      the pattern of hemispheric specialization observed here yields new insights into
      sex differences in face perception and entails further questions about
      interactions between biological sex, psychological gender and influences that
      might be stimulus-driven or task dependent. 

PMID- 23874882
TI  - Loss of Notch1 disrupts the barrier repair in the corneal epithelium.
AB  - The corneal epithelium is the outermost layer of the cornea that directly faces
      the outside environment, hence it plays a critical barrier function. Previously,
      conditional loss of Notch1 on the ocular surface was found to cause inflammation
      and keratinization of the corneal epithelium. This was in part attributed to
      impaired vitamin A metabolism, loss of the meibomian glands and recurrent eyelid
      trauma. We hypothesized that Notch1 plays an essential role in the corneal
      epithelial barrier function and is a contributing factor in the pathologic
      changes in these mice. Notch1 was conditionally deleted in adult
      Notch1(flox/flox), K14-Cre-ERT(+/-) mice using hydroxy-tamoxifen. The results
      indicated that conditional deletion of Notch1 on the ocular surface leads to
      progressive impairment of the epithelial barrier function before the onset of
      corneal opacification and keratinization. Loss of the barrier was demonstrated
      both by an increase in in vivo corneal fluorescein staining and by enhanced
      penetration of a small molecule through the epithelium. Corneal epithelial
      wounding resulted in significant delay in recovery of the barrier function in
      conditional Notch1(-/-) mice compared to wild type. Mice with conditional
      deletion of Notch1 did not demonstrate any evidence of dry eyes based on aqueous
      tear production and had normal conjunctival goblet cells. In a calcium switch
      experiment in vitro, Notch1(-/-) cells demonstrated delayed membrane localization
      of the tight junction protein ZO-1 consistent with a defect in the epithelial
      tight junction formation. These findings highlight the role of Notch1 in
      epithelial differentiation and suggest that intrinsic defects in the corneal
      epithelial barrier recovery after wounding is an important contributing factor to
      the development of inflammatory keratinization in Notch1(-/-) mice. 

PMID- 23874883
TI  - Adenosine 2A receptor antagonist prevented and reversed liver fibrosis in a mouse
      model of ethanol-exacerbated liver fibrosis.
AB  - The effect of moderate alcohol consumption on liver fibrosis is not well
      understood, but evidence suggests that adenosine may play a role in mediating the
      effects of moderate ethanol on tissue injury. Ethanol increases the concentration
      of adenosine in the liver. Adenosine 2A receptor (A2AR) activation is known to
      enhance hepatic stellate cell (HSC) activation and A2AR deficient mice are
      protected from fibrosis in mice. Making use of a novel mouse model of moderate
      ethanol consumption in which female C57BL/6J mice were allowed continued access
      to 2% (vol/vol) ethanol (11% calories) or pair-fed control diets for 2 days, 2
      weeks or 5 weeks and superimposed with exposure to CCl4, we tested the hypothesis
      that moderate ethanol consumption increases fibrosis in response to carbon
      tetrachloride (CCl4) and that treatment of mice with an A2AR antagonist prevents
      and/or reverses this ethanol-induced increase in liver fibrosis. Neither the
      expression or activity of CYP2E1, required for bio-activation of CCl4, nor AST
      and ALT activity in the plasma were affected by ethanol, indicating that moderate
      ethanol did not increase the direct hepatotoxicity of CCl4. However, ethanol
      feeding enhanced HSC activation and exacerbated liver fibrosis upon exposure to
      CCl4. This was associated with an increased sinusoidal angiogenic response in the
      liver. Treatment with A2AR antagonist both prevented and reversed the ability of
      ethanol to exacerbate liver fibrosis. CONCLUSION: Moderate ethanol consumption
      exacerbates hepatic fibrosis upon exposure to CCl4. A2AR antagonism may be a
      potential pharmaceutical intervention to decrease hepatic fibrosis in response to
      ethanol.

PMID- 23874884
TI  - Plasmodium falciparum expressing domain cassette 5 type PfEMP1 (DC5-PfEMP1) bind
      PECAM1.
AB  - Members of the Plasmodium falciparum Erythrocyte Membrane protein 1 (PfEMP1)
      family expressed on the surface of malaria-infected erythrocytes mediate binding
      of the parasite to different receptors on the vascular lining. This process
      drives pathologies, and severe childhood malaria has been associated with the
      expression of particular subsets of PfEMP1 molecules. PfEMP1 are grouped into
      subtypes based on upstream sequences and the presence of semi-conserved PfEMP1
      domain compositions named domain cassettes (DCs). Earlier studies have indicated
      that DC5-containing PfEMP1 (DC5-PfEMP1) are more likely to be expressed in
      children with severe malaria disease than in children with uncomplicated malaria,
      but these PfEMP1 subtypes only dominate in a relatively small proportion of the
      children with severe disease. In this study, we have characterised the genomic
      sequence characteristic for DC5, and show that two genetically different parasite
      lines expressing DC5-PfEMP1 bind PECAM1, and that anti-DC5-specific antibodies
      inhibit binding of DC5-PfEMP1-expressing parasites to transformed human bone
      marrow endothelial cells (TrHBMEC). We also show that antibodies against each of
      the four domains characteristic for DC5 react with native PfEMP1 expressed on the
      surface of infected erythrocytes, and that some of these antibodies are cross
      reactive between the two DC5-containing PfEMP1 molecules tested. Finally, we
      confirm that anti-DC5 antibodies are acquired early in life by individuals living
      in malaria endemic areas, that individuals having high levels of these antibodies
      are less likely to develop febrile malaria episodes and that the antibody levels
      correlate positively with hemoglobin levels. 

PMID- 23874885
TI  - Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma
      biomarkers for rheumatoid arthritis.
AB  - MicroRNAs (miRNAs) are present in human plasma and known as a non-invasive
      biomarker for cancer detection. Our study was designed to identify plasma miRNAs
      specific for rheumatoid arthritis (RA) by a comprehensive array approach. We
      performed a systematic, array-based miRNA analysis on plasma samples from three
      RA patients and three healthy controls (HCs). Plasma miRNAs with more than four
      times change or with significant (P<0.05) change in expression, or detectable
      only in RA plasma, were confirmed with plasma from eight RA patients and eight
      HCs using real-time quantitative PCR. Consistently detectable miRNAs that were
      significantly different between RA patients and HCs were chosen for further
      validation with 102 RA patients and 104 HCs. The area under curves (AUC) were
      calculated after plotting the receiver operating characteristic (ROC) curves. To
      determine if these miRNAs are specific for RA, the concentrations of these miRNAs
      were analyzed in 24 patients with osteoarthritis (OA), and 11 patients with
      systemic lupus erythematosus (SLE). The array analysis and the subsequent
      confirmation in larger patient cohort identified significant alterations in
      plasma levels of seven miRNAs. The highest AUC was found for miR-125a-5p,
      followed in order by miR-24 and miR-26a. Multivariable logistic regression
      analysis showed that miR-24, miR-30a-5p, and miR-125a-5p were crucial factors for
      making detection model of RA and provided a formula for Estimated Probability of
      RA by plasma MiRNA (ePRAM), employing miR-24, miR-30a-5p and miR-125a-5p, which
      showed increased diagnostic accuracy (AUC: 0.89). The level of miR-24, miR-125a
      5p, and ePRAM in OA and SLE patients were lower than that in RA. There was no
      significant difference in detection for anti-citrullinated protein antibody
      (ACPA)-positive and ACPA-negative RA patients. These results suggest that the
      plasma concentrations of miR-24 and miR-125a-5p, and ePRAM are potential
      diagnostic markers of RA even if patients were ACPA-negative. 

PMID- 23874887
TI  - Observations of immuno-gold conjugates on influenza viruses using waveguide-mode
      sensors.
AB  - Gold nanoparticles were conjugated to an antibody (immuno-AuNP) against
      A/Udorn/307/1972 (H3N2) influenza virus to detect viruses on a sensing plate
      designed for an evanescent field-coupled waveguide-mode sensor. Experiments were
      conducted using human influenza A/H3N2 strains, and immuno-AuNP could detect
      8*10(5) PFU/ml (40 pg/ul) intact A/Udorn/307/1972 and 120 pg/ul
      A/Brisbane/10/2007. Furthermore, increased signal magnitude was achieved in the
      presence of non-ionic detergent, as the virtual detection level was increased to
      8*10(4) PFU/ml A/Udorn/307/1972. Immuno-AuNPs were then complexed with viruses to
      permit direct observation, and they formed a ring of confined nanodots on the
      membrane of both intact and detergent-treated viruses as directly visualized by
      scanning electron microscopy. With this complex the detection limit was improved
      further to 8*10(3) PFU/ml on anti-rabbit IgG immobilized sensing plate. These
      strategies introduce methods for observing trapped intact viruses on the sensing
      plates generated for optical systems. 

PMID- 23874886
TI  - Homo floresiensis contextualized: a geometric morphometric comparative analysis
      of fossil and pathological human samples.
AB  - The origin of hominins found on the remote Indonesian island of Flores remains
      highly contentious. These specimens may represent a new hominin species, Homo
      floresiensis, descended from a local population of Homo erectus or from an
      earlier (pre-H. erectus) migration of a small-bodied and small-brained hominin
      out of Africa. Alternatively, some workers suggest that some or all of the
      specimens recovered from Liang Bua are pathological members of a small-bodied
      modern human population. Pathological conditions proposed to explain their
      documented anatomical features include microcephaly, myxoedematous endemic
      hypothyroidism ("cretinism") and Laron syndrome (primary growth hormone
      insensitivity). This study evaluates evolutionary and pathological hypotheses
      through comparative analysis of cranial morphology. Geometric morphometric
      analyses of landmark data show that the sole Flores cranium (LB1) is clearly
      distinct from healthy modern humans and from those exhibiting hypothyroidism and
      Laron syndrome. Modern human microcephalic specimens converge, to some extent, on
      crania of extinct species of Homo. However in the features that distinguish these
      two groups, LB1 consistently groups with fossil hominins and is most similar to
      H. erectus. Our study provides further support for recognizing the Flores
      hominins as a distinct species, H. floresiensis, whose affinities lie with
      archaic Homo. 

PMID- 23874888
TI  - Bodychecking rules and concussion in elite hockey.
AB  - Athletes participating in contact sports such as ice hockey are exposed to a high
      risk of suffering a concussion. We determined whether recent rule changes
      regulating contact to the head introduced in 2010-11 and 2011-12 have been
      effective in reducing the incidence of concussion in the National Hockey League
      (NHL). A league with a longstanding ban on hits contacting the head, the Ontario
      Hockey League (OHL), was also studied. A retrospective study of NHL and OHL games
      for the 2009-10 to 2011-12 seasons was performed using official game records and
      team injury reports in addition to other media sources. Concussion incidence over
      the 3 seasons analyzed was 5.23 per 100 NHL regular season games and 5.05 per 100
      OHL regular season games (IRR 1.04; 95% CI 1.01, 1.50). When injuries described
      as concussion-like or suspicious of concussion were included, incidences rose to
      8.8 and 7.1 per 100 games respectively (IRR 1.23; 95% CI 0.81, 1.32). The number
      of NHL concussions or suspected concussions was lower in 2009-10 than in 2010-11
      (IRR 0.61; 95% CI 0.45, 0.83), but did not increase from 2010-11 to 2011-12 (IRR
      1.05; 95% CI 0.80, 1.38). 64.2% of NHL concussions were caused by bodychecking,
      and only 28.4% of concussions and 36.8% of suspected concussions were caused by
      illegal incidents. We conclude that rules regulating bodychecking to the head did
      not reduce the number of players suffering concussions during NHL regular season
      play and that further changes or stricter enforcement of existing rules may be
      required to minimize the risk of players suffering these injuries. 

PMID- 23874889
TI  - Structural and functional characterisation of TesA - a novel lysophospholipase A
      from Pseudomonas aeruginosa.
AB  - TesA from Pseudomonas aeruginosa belongs to the GDSL hydrolase family of serine
      esterases and lipases that possess a broad substrate- and regiospecificity. It
      shows high sequence homology to TAP, a multifunctional enzyme from Escherichia
      coli exhibiting thioesterase, lysophospholipase A, protease and arylesterase
      activities. Recently, we demonstrated high arylesterase activity for TesA, but
      only minor thioesterase and no protease activity. Here, we present a comparative
      analysis of TesA and TAP at the structural, biochemical and physiological levels.
      The crystal structure of TesA was determined at 1.9 A and structural differences
      were identified, providing a possible explanation for the differences in
      substrate specificities. The comparison of TesA with other GDSL-hydrolase
      structures revealed that the flexibility of active-site loops significantly
      affects their substrate specificity. This assumption was tested using a rational
      approach: we have engineered the putative coenzyme A thioester binding site of E.
      coli TAP into TesA of P. aeruginosa by introducing mutations D17S and L162R. This
      TesA variant showed increased thioesterase activity comparable to that of TAP.
      TesA is the first lysophospholipase A described for the opportunistic human
      pathogen P. aeruginosa. The enzyme is localized in the periplasm and may exert
      important functions in the homeostasis of phospholipids or detoxification of
      lysophospholipids. 

PMID- 23874890
TI  - Hypoxia modulates fibroblastic architecture, adhesion and migration: a role for
      HIF-1alpha in cofilin regulation and cytoplasmic actin distribution.
AB  - Cells can adapt to hypoxia by various mechanisms. Yet, hypoxia-induced effects on
      the cytoskeleton-based cell architecture and functions are largely unknown. Here
      we present a comprehensive analysis of the architecture and function of L929
      fibroblasts under hypoxic conditions (1% O2). Cells cultivated in hypoxia showed
      striking morphological differences as compared to cells cultivated under normoxic
      conditions (20% O2). These changes include an enlargement of cell area and
      volume, increased numbers of focal contacts and loss of cell polarization.
      Furthermore the beta- and gamma-actin distribution is greatly altered. These
      hypoxic adjustments are associated with enhanced cell spreading and a decline of
      cell motility in wound closure and single cell motility assays. As the hypoxia
      inducible factor-1alpha (HIF-1alpha) is stabilised in hypoxia and plays a pivotal
      role in the transcriptional response to changes in oxygen availability we used an
      shRNA-approach to examine the role of HIF-1alpha in cytoskeleton-related
      architecture and functions. We show that the observed increase in cell area,
      actin filament rearrangement, decrease of single cell migration in hypoxia and
      the maintenance of p-cofilin levels is dependent on HIF-1alpha stabilisation. 

PMID- 23874891
TI  - Prevalence of HIV and syphilis infection among high school and college student
      MSM in China: a systematic review and meta-analysis.
AB  - OBJECTIVES: The aim of this study is to systematically review the published
      studies and summarize the estimates of HIV and syphilis prevalences among high
      school and college student MSM in China in order to provide information for
      conducting targeted interventions. METHODS: Pubmed, Chinese National Knowledge
      Infrastructure, Wanfang and Google Scholar databases were searched in January
      2013 to identify relevant articles. Data of eligible citations were extracted by
      two reviewers. All analyses were performed using Comprehensive Meta-Analysis V2.0
      and SPSS V17.0. RESULTS: Twenty-four eligible studies (6 in English and 18 in
      Chinese), published between 2006 and 2012, with a total of 3083 student MSM
      participants, were included. The meta-analyses showed that the prevalences of HIV
      and syphilis among studied student MSM were 4.4% (95% CI: 3.0%, 6.4%) and 5.7%
      (95% CI: 4.8%, 6.7%), respectively. HIV prevalence increased over the study
      period (3.0% in 2003-2006; 4.5% in 2007-2008, and 6.8% in 2009-2010, trend test
      chi-square =11.3, p = 0.001). CONCLUSIONS: Student MSM have become high-risk
      populations for HIV infection in China. The high prevalence of syphilis and the
      increasing HIV prevalence trend indicate the potential for a more severe HIV
      epidemic. Comprehensive intervention strategies that address condom promotion,
      syphilis detection and treatment, and health education need to be tailored to
      this vulnerable population to prevent HIV and syphilis infections.

PMID- 23874892
TI  - Conditional VHL gene deletion causes hypoglycemic death associated with
      disproportionately increased glucose uptake by hepatocytes through an upregulated
      IGF-I receptor.
AB  - Our conditional VHL knockout (VHL-KO) mice, having VHL gene deletion induced by
      tamoxifen, developed severe hypoglycemia associated with disproportionately
      increased storage of PAS-positive substances in the liver and resulted in the
      death of these mice. This hypoglycemic state was neither due to impaired insulin
      secretion nor insulin receptor hypersensitivity. By focusing on insulin-like
      growth factor I (IGF-I), which has a similar effect on glucose metabolism as the
      insulin receptor, we demonstrated that IGF-I receptor (IGF-IR) protein expression
      in the liver was upregulated in VHL-KO mice compared to that in the mice without
      VHL deletion, as was the expression of glucose transporter (GLUT) 1. The
      interaction of the receptor for activated C kinase (RACK) 1, which predominantly
      binds to VHL, was enhanced in VHL-KO livers with IGF-IR, because VHL deletion
      increased free RACK1 and facilitated the IGF-IR-RACKI interaction. An IGF-IR
      antagonist retarded hypoglycemic progression and sustained an euglycemic state.
      These IGF-IR antagonist effects on restoring blood glucose levels also attenuated
      PAS-positive substance storage in the liver. Because the effect of IGF-I on HIF
      1alpha protein synthesis is mediated by IGF-IR, our results indicated that VHL
      inactivation accelerated hepatic glucose storage through the upregulation of IGF
      IR and GLUT1 and that IGF-IR was a key regulator in VHL-deficient hepatocytes. 

PMID- 23874893
TI  - Prevalence, comorbidity and heritability of hoarding symptoms in adolescence: a
      population based twin study in 15-year olds.
AB  - BACKGROUND: Hoarding Disorder (HD) is often assumed to be an 'old age' problem,
      but many individuals diagnosed with HD retrospectively report first experiencing
      symptoms in childhood or adolescence. We examined the prevalence, comorbidity and
      etiology of hoarding symptoms in adolescence. METHODS: To determine the presence
      of clinically significant hoarding symptoms, a population-based sample of 15-year
      old twins (N = 3,974) completed the Hoarding Rating Scale-Self Report. Co
      occurring Obsessive Compulsive Disorder (OCD), Autism Spectrum Disorders (ASD)
      and Attention Deficit Hyperactivity Disorder (ADHD) were estimated from parental
      report. Model-fitting analyses divided hoarding symptom scores into additive
      genetic, shared, and non-shared environmental effects. RESULTS: The prevalence of
      clinically significant hoarding symptoms was 2% (95% CI 1.6-2.5%), with a
      significantly higher prevalence in girls than boys. Exclusion of the clutter
      criterion (as adolescents do not have control over their environment) increased
      the prevalence rate to 3.7% (95% CI 3.1-4.3%). Excessive acquisition was reported
      by 30-40% among those with clinically significant hoarding symptoms. The
      prevalence of co-occurring OCD (2.9%), ASD (2.9%) and ADHD (10.0%) was comparable
      in hoarding and non-hoarding teenagers. Model-fitting analyses suggested that, in
      boys, additive genetic (32%; 95% CI 13-44%) and non-shared environmental effects
      accounted for most of the variance. In contrast, among girls, shared and non
      shared environmental effects explained most of the variance, while additive
      genetic factors played a negligible role. CONCLUSIONS: Hoarding symptoms are
      relatively prevalent in adolescents, particularly in girls, and cause distress
      and/or impairment. Hoarding was rarely associated with other common
      neurodevelopmental disorders, supporting its DSM-5 status as an independent
      diagnosis. The relative importance of genetic and shared environmental factors
      for hoarding differed across sexes. The findings are suggestive of dynamic
      developmental genetic and environmental effects operating from adolescence onto
      adulthood.

PMID- 23874895
TI  - Effect of epicatechin against radiation-induced oral mucositis: in vitro and in
      vivo study.
AB  - PURPOSE: Radiation-induced oral mucositis limits the delivery of high-dose
      radiation to head and neck cancer. This study investigated the effectiveness of
      epicatechin (EC), a component of green tea extracts, on radiation-induced oral
      mucositis in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of EC on
      radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT.
      Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP),
      reactive oxygen species (ROS) generation and changes in the signaling pathway
      were investigated. In vivo therapeutic effects of EC for oral mucositis were
      explored in a rat model. Rats were monitored by daily inspections of the oral
      cavity, amount of oral intake, weight change and survival rate. For
      histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were
      performed. RESULTS: EC significantly inhibited radiation-induced apoptosis,
      change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment
      markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after
      irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed
      decreased oral intake, weight and survival rate, but oral administration of EC
      significantly restored all three parameters. Histopathologic changes were
      significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat
      oral mucosa revealed that EC treatment significantly decreased radiation-induced
      apoptotic cells. CONCLUSIONS: This study suggests that EC significantly inhibited
      radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a
      safe and effective candidate treatment for the prevention of radiation-induced
      mucositis.

PMID- 23874896
TI  - Roles for ordered and bulk solvent in ligand recognition and docking in two
      related cavities.
AB  - A key challenge in structure-based discovery is accounting for modulation of
      protein-ligand interactions by ordered and bulk solvent. To investigate this, we
      compared ligand binding to a buried cavity in Cytochrome c Peroxidase (CcP),
      where affinity is dominated by a single ionic interaction, versus a cavity
      variant partly opened to solvent by loop deletion. This opening had unexpected
      effects on ligand orientation, affinity, and ordered water structure. Some
      ligands lost over ten-fold in affinity and reoriented in the cavity, while others
      retained their geometries, formed new interactions with water networks, and
      improved affinity. To test our ability to discover new ligands against this
      opened site prospectively, a 534,000 fragment library was docked against the open
      cavity using two models of ligand solvation. Using an older solvation model that
      prioritized many neutral molecules, three such uncharged docking hits were
      tested, none of which was observed to bind; these molecules were not highly
      ranked by the new, context-dependent solvation score. Using this new method,
      another 15 highly-ranked molecules were tested for binding. In contrast to the
      previous result, 14 of these bound detectably, with affinities ranging from 8 uM
      to 2 mM. In crystal structures, four of these new ligands superposed well with
      the docking predictions but two did not, reflecting unanticipated interactions
      with newly ordered waters molecules. Comparing recognition between this open
      cavity and its buried analog begins to isolate the roles of ordered solvent in a
      system that lends itself readily to prospective testing and that may be broadly
      useful to the community. 

PMID- 23874897
TI  - The short- and long-term risk of stroke after herpes zoster - a nationwide
      population-based cohort study.
AB  - BACKGROUND AND OBJECTIVE: Varicella zoster virus (VZV) is known to cause VZV
      vasculopathy, which may be associated with stroke. A recent study found an
      increased risk of stroke within one year of herpes zoster. We aimed to
      investigate the short and long-term effects of herpes zoster on the risk of
      stroke. METHODS: Using Danish national registers, we constructed a cohort
      consisting of all Danish adults >=18 years old between 1995 and 2008 (n = 4.6
      million; person-years of follow-up = 52.9 million). Individual-level information
      on prescriptions for herpes zoster antiviral treatment and diagnoses of stroke
      was obtained from national registers. We compared the risk of stroke in persons
      who had received the specific dosage of acyclovir for herpes zoster with persons
      who had never received antiviral treatment by Poisson regression. RESULTS: During
      follow-up, 2.5% received treatment for herpes zoster and 5.0% were diagnosed with
      stroke. Individuals who had received medication had a 127% (95% CI 83-182%)
      increased risk the first two weeks, 17% (CI 9-24%) between two weeks and one
      year, and 5% (2-9%) after the first year. The increased risk was greatest in the
      youngest age group (<40). To control for healthcare-seeking behaviour, we
      conducted parallel analyses investigating the risk of selected fractures after
      herpes zoster and found no similar increased risks. CONCLUSIONS: This large
      nationwide cohort study found an increased risk of stroke after treatment for
      herpes zoster. Although the short-term risk was particularly high, we cannot rule
      out the possibility of a small but important long-term risk.

PMID- 23874898
TI  - Relaxation along a fictitious field (RAFF) and Z-spectroscopy using alternating
      phase irradiation (ZAPI) in permanent focal cerebral ischemia in rat.
AB  - Cerebral ischemia alters the molecular dynamics and content of water in brain
      tissue, which is reflected in NMR relaxation, diffusion and magnetization
      transfer (MT) parameters. In this study, the behavior of two new MRI contrasts,
      Relaxation Along a Fictitious Field (RAFF) and Z-spectroscopy using Alternating
      Phase Irradiation (ZAPI), were quantified together with conventional relaxation
      parameters (T1, T2 and T1rho) and MT ratios in acute cerebral ischemia in rat.
      The right middle cerebral artery was permanently occluded and quantitative MRI
      data was acquired sequentially for the above parameters for up to 6 hours. The
      following conclusions were drawn: 1) Time-dependent changes in RAFF and T1rho
      relaxation are not coupled to those in MT. 2) RAFF relaxation evolves more like
      transverse, rather than longitudinal relaxation. 3) MT measured with ZAPI is less
      sensitive to ischemia than conventional MT. 4) ZAPI data suggest alterations in
      the T2 distribution of macromolecules in acute cerebral ischemia. It was shown
      that both RAFF and ZAPI provide complementary MRI information from acute ischemic
      brain tissue. The presented multiparametric MRI data may aid in the assessment of
      brain tissue status early in ischemic stroke. 

PMID- 23874899
TI  - Repeated measurement of the intermountain risk score enhances prognostication for
      mortality.
AB  - BACKGROUND: The Intermountain Risk Score (IMRS), composed of the complete blood
      count (CBC) and basic metabolic profile (BMP), predicts mortality and morbidity
      in medical and general populations. Whether longitudinal repeated measurement of
      IMRS is useful for prognostication is an important question for its clinical
      applicability. METHODS: Females (N = 5,698) and males (N = 5,437) with CBC and
      BMP panels measured 6 months to 2.0 years apart (mean 1.0 year) had baseline and
      follow-up IMRS computed. Survival analysis during 4.0+/-2.5 years (maximum 10
      years) evaluated mortality (females: n = 1,255 deaths; males: n = 1,164 deaths)
      and incident major events (myocardial infarction, heart failure [HF], and
      stroke). RESULTS: Both baseline and follow-up IMRS (categorized as high-risk vs.
      low-risk) were independently associated with mortality (all p<0.001) in
      bivariable models. For females, follow-up IMRS had hazard ratio (HR) = 5.23 (95%
      confidence interval [CI] = 4.11, 6.64) and baseline IMRS had HR = 3.66 (CI =
      2.94, 4.55). Among males, follow-up IMRS had HR = 4.28 (CI = 3.51, 5.22) and
      baseline IMRS had HR = 2.32 (CI = 1.91, 2.82). IMRS components such as RDW,
      measured at both time points, also predicted mortality. Baseline and follow-up
      IMRS strongly predicted incident HF in both genders. CONCLUSIONS: Repeated
      measurement of IMRS at baseline and at about one year of follow-up were
      independently prognostic for mortality and incident HF among initially
      hospitalized patients. RDW and other CBC and BMP values were also predictive of
      outcomes. Further research should evaluate the utility of IMRS as a tool for
      clinical risk adjustment.

PMID- 23874894
TI  - Sexually-transmitted/founder HIV-1 cannot be directly predicted from plasma or
      PBMC-derived viral quasispecies in the transmitting partner.
AB  - OBJECTIVE: Characterization of HIV-1 sequences in newly infected individuals is
      important for elucidating the mechanisms of viral sexual transmission. We report
      the identification of transmitted/founder viruses in eight pairs of HIV-1
      sexually-infected patients enrolled at the time of primary infection
      ("recipients") and their transmitting partners ("donors"). METHODS: Using a
      single genome-amplification approach, we compared quasispecies in donors and
      recipients on the basis of 316 and 376 C2V5 env sequences amplified from plasma
      viral RNA and PBMC-associated DNA, respectively. RESULTS: Both DNA and RNA
      sequences indicated very homogeneous viral populations in all recipients,
      suggesting transmission of a single variant, even in cases of recent sexually
      transmitted infections (STIs) in donors (n = 2) or recipients (n = 3). In all
      pairs, the transmitted/founder virus was derived from an infrequent variant
      population within the blood of the donor. The donor variant sequences most
      closely related to the recipient sequences were found in plasma samples in 3/8
      cases and/or in PBMC samples in 6/8 cases. Although donors were exclusively (n =
      4) or predominantly (n = 4) infected by CCR5-tropic (R5) strains, two recipients
      were infected with highly homogeneous CXCR4/dual-mixed-tropic (X4/DM) viral
      populations, identified in both DNA and RNA. The proportion of X4/DM quasispecies
      in donors was higher in cases of X4/DM than R5 HIV transmission (16.7-22.0%
      versus 0-2.6%), suggesting that X4/DM transmission may be associated with a
      threshold population of X4/DM circulating quasispecies in donors. CONCLUSIONS:
      These suggest that a severe genetic bottleneck occurs during subtype B HIV-1
      heterosexual and homosexual transmission. Sexually-transmitted/founder virus
      cannot be directly predicted by analysis of the donor's quasispecies in plasma
      and/or PBMC. Additional studies are required to fully understand the traits that
      confer the capacity to transmit and establish infection, and determine the role
      of concomitant STIs in mitigating the genetic bottleneck in mucosal HIV
      transmission.

PMID- 23874900
TI  - A serpin released by an entomopathogen impairs clot formation in insect defense
      system.
AB  - Steinernema carpocapsae is an entomopathogenic nematode widely used for the
      control of insect pests due to its virulence, which is mainly attributed to the
      ability the parasitic stage has to overcome insect defences. To identify the
      mechanisms underlying such a characteristic, we studied a novel serpin-like
      inhibitor (sc-srp-6) that was detected in a transcriptome analysis. Recombinant
      Sc-SRP-6 produced in Escherichia coli had a native fold of serpins belonging to
      the alpha-1-peptidase family and exhibited inhibitory activity against trypsin
      and alpha-chymotrypsin with Ki of 0.42 * 10(-7) M and 1.22 * 10(-7) M,
      respectively. Functional analysis revealed that Sc-SRP-6 inhibits insect
      digestive enzymes, thus preventing the hydrolysis of ingested particles.
      Moreover, Sc-SRP-6 impaired the formation of hard clots at the injury site, a
      major insect defence mechanism against invasive pathogens. Sc-SRP-6 does not
      prevent the formation of clot fibres and the activation of prophenoloxidases but
      impairs the incorporation of the melanin into the clot. Binding assays showed a
      complex formation between Sc-SRP-6 and three proteins in the hemolymph of
      lepidopteran required for clotting, apolipophorin, hexamerin and trypsin-like,
      although the catalytic inhibition occurred exclusively in trypsin-like. This data
      allowed the conclusion that Sc-SRP-6 promotes nematode virulence by inhibiting
      insect gut juices and by impairing immune clot reaction.

PMID- 23874901
TI  - Distinct features of auditory steady-state responses as compared to transient
      event-related potentials.
AB  - Transient event-related potentials (ERPs) and steady-state responses (SSRs) have
      been popularly employed to investigate the function of the human brain, but their
      relationship still remains a matter of debate. Some researchers believed that
      SSRs could be explained by the linear summation of successive transient ERPs
      (superposition hypothesis), while others believed that SSRs were the result of
      the entrainment of a neural rhythm driven by the periodic repetition of a sensory
      stimulus (oscillatory entrainment hypothesis). In the present study, taking
      auditory modality as an example, we aimed to clarify the distinct features of
      SSRs, evoked by the 40-Hz and 60-Hz periodic auditory stimulation, as compared to
      transient ERPs, evoked by a single click. We observed that (1) SSRs were mainly
      generated by phase synchronization, while late latency responses (LLRs) in
      transient ERPs were mainly generated by power enhancement; (2) scalp topographies
      of LLRs in transient ERPs were markedly different from those of SSRs; (3) the
      powers of both 40-Hz and 60-Hz SSRs were significantly correlated, while they
      were not significantly correlated with the N1 power in transient ERPs; (4)
      whereas SSRs were dominantly modulated by stimulus intensity, middle latency
      responses (MLRs) were not significantly modulated by both stimulus intensity and
      subjective loudness judgment, and LLRs were significantly modulated by subjective
      loudness judgment even within the same stimulus intensity. All these findings
      indicated that high-frequency SSRs were different from both MLRs and LLRs in
      transient ERPs, thus supporting the possibility of oscillatory entrainment
      hypothesis to the generation of SSRs. Therefore, SSRs could be used to explore
      distinct neural responses as compared to transient ERPs, and help us reveal novel
      and reliable neural mechanisms of the human brain. 

PMID- 23874902
TI  - Association between IL28B polymorphisms and spontaneous clearance of hepatitis B
      virus infection.
AB  - BACKGROUND/AIMS: Single-nucleotide polymorphisms (SNPs) near the interleukin 28B
      gene (IL28B; interferon [IFN]-lambda-3) are associated with outcomes of chronic
      hepatitis C virus (HCV) and hepatitis B virus (HBV) infection treated with
      peginterferon (PEG-IFN) alpha-based antiviral therapy. In this study, we
      investigated the influence of IL28B polymorphisms on spontaneous clearance of HBV
      infection in a large Korean cohort. METHODS: Between January 2007 and June 2010,
      a total of 208 patients with chronic HBV infection and newly diagnosed HBV
      related hepatocellular carcinoma were recruited as the CC group [HBsAg(+) for >6
      months, anti-HBc(+), and anti-HBs(-)]. In addition, 351 organ donors were
      stratified into the UE group [n = 106; HBsAg(-), anti-HBc(-), and anti-HBs(-)] or
      the SC group [n = 245; HBsAg(-), anti-HBc(+), and anti-HBs(+)]. The SNaPshot
      ddNTP Primer Extension Kit (Applied Biosystems, Foster City, CA) was used for SNP
      detection. Direct full sequencing of the IL28B coding region was attempted.
      RESULTS: Regardless of group, rs12979860 CC was most frequently identified (85.0%
      in UE, 85.9% in SC, and 93.5% in CC, respectively), whereas rs12979860 TT was not
      identified in any group. Similarly, rs12980275 AA and rs8099917 TT were most
      frequently identified (>=85%) regardless of group, whereas rs12980275 GG was
      identified in only one subject in the SC group. In addition, rs8099917 GG was not
      identified. The prevalences of CC in rs12979860, AA in rs12980275, and TT in
      rs8099917 were significantly higher in the CC group when compared with the UE and
      SC group (all P<0.05). Among 19 novel SNPs in the IL28B coding region, the
      proportions of 6 SNPs were significantly different among the UE, SC, and CC
      groups (all P<0.05). CONCLUSIONS: The SNP upstream of IL28B that has the
      strongest genetic association with HCV recovery has an inverse influence on HBV
      recovery. Additional studies are needed to understand the mechanisms of this SNP
      in HBV infection.

PMID- 23874903
TI  - De novo assembly and characterization of the Barnyardgrass (Echinochloa crus
      galli) transcriptome using next-generation pyrosequencing.
AB  - BACKGROUND: Barnyardgrass (Echinochloa crus-galli) is an important weed that is a
      menace to rice cultivation and production. Rapid evolution of herbicide
      resistance in this weed makes it one of the most difficult to manage using
      herbicides. Since genome-wide sequence data for barnyardgrass is limited, we
      sequenced the transcriptomes of susceptible and resistant barnyardgrass biotypes
      using the 454 GS-FLX platform. RESULTS: 454 pyrosequencing generated 371,281 raw
      reads with an average length of 341.8 bp, which made a total length of 126.89 Mb
      (SRX160526). De novo assembly produced 10,142 contigs (~5.92 Mb) with an average
      length of 583 bp and 68,940 singletons (~22.13 Mb) with an average length of 321
      bp. About 244,653 GO term assignments to the biological process, cellular
      component and molecular function categories were obtained. A total of 6,092
      contigs and singletons with 2,515 enzyme commission numbers were assigned to 151
      predicted KEGG metabolic pathways. Digital abundance analysis using Illumina
      sequencing identified 78,124 transcripts among susceptible, resistant, herbicide
      treated susceptible and herbicide-treated resistant barnyardgrass biotypes. From
      these analyses, eight herbicide target-site gene groups and four non-target-site
      gene groups were identified in the resistant biotype. These could be potential
      candidate genes involved in the herbicide resistance of barnyardgrass and could
      be used for further functional genomics research. C4 photosynthesis genes
      including RbcS, RbcL, NADP-me and MDH with complete CDS were identified using PCR
      and RACE technology. CONCLUSIONS: This is the first large-scale transcriptome
      sequencing of E. crus-galli performed using the 454 GS-FLX platform. Potential
      candidate genes involved in the evolution of herbicide resistance were identified
      from the assembled sequences. This transcriptome data may serve as a reference
      for further gene expression and functional genomics studies, and will facilitate
      the study of herbicide resistance at the molecular level in this species as well
      as other weeds.

PMID- 23874904
TI  - Dimensions and determinants of trust in health care in resource poor settings--a
      qualitative exploration.
AB  - BACKGROUND: Trust in health care has been intensely researched in resource rich
      settings. Some studies in resource poor settings suggest that the dimensions and
      determinants of trust are likely to be different. OBJECTIVES: This study was done
      as a qualitative exploration of the dimensions and determinants of trust in
      health care in Tamil Nadu, a state in south India to assess the differences from
      dimensions and determinants in resource rich settings. METHODOLOGY: The
      participants included people belonging to marginalized communities with poor
      access to health care services and living in conditions of resource deprivation.
      A total of thirty five in depth interviews were conducted. The interviews were
      summarized and transcribed and data were analyzed following thematic analysis and
      grounded theory approach. RESULTS: The key dimensions of trust in health care
      identified during the interviews were perceived competence, assurance of
      treatment irrespective of ability to pay or at any time of the day, patients'
      willingness to accept drawbacks in health care, loyalty to the physician and
      respect for the physician. Comfort with the physician and health facility,
      personal involvement of the doctor with the patient, behavior and approach of
      doctor, economic factors, and health awareness were identified as factors
      determining the levels of trust in health care. CONCLUSIONS: The dimensions and
      determinants of trust in health care in resource poor settings are different from
      that in resource rich settings. There is a need to develop scales to measure
      trust in health care in resource poor settings using these specific dimensions
      and determinants.

PMID- 23874905
TI  - Hierarchical dynamics of ecological communities: do scales of space and time
      match?
AB  - Theory posits that community dynamics organize at distinct hierarchical scales of
      space and time, and that the spatial and temporal patterns at each scale are
      commensurate. Here we use time series modeling to investigate fluctuation
      frequencies of species groups within invertebrate metacommunities in 26 boreal
      lakes over a 20-year period, and variance partitioning analysis to study whether
      species groups with different fluctuation patterns show spatial signals that are
      commensurate with the scale-specific fluctuation patterns identified. We
      identified two groups of invertebrates representing hierarchically organized
      temporal dynamics: one species group showed temporal variability at decadal
      scales (slow patterns of change), whilst another group showed fluctuations at 3
      to 5-year intervals (faster change). This pattern was consistently found across
      all lakes studied. A spatial signal was evident in the slow but not faster
      changing species groups. As expected, the spatial signal for the slow-changing
      group coincided with broad-scale spatial patterns that could be explained with
      historical biogeography (ecoregion delineation, and dispersal limitation assessed
      through a dispersal trait analysis). In addition to spatial factors, the slow
      changing groups correlated with environmental variables, supporting the
      conjecture that boreal lakes are undergoing environmental change. Taken together
      our results suggest that regionally distinct sets of taxa, separated by
      biogeographical boundaries, responded similarly to broad-scale environmental
      change. Not only does our approach allow testing theory about hierarchically
      structured space-time patterns; more generally, it allows assessing the relative
      role of the ability of communities to track environmental change and dispersal
      constraints limiting community structure and biodiversity at macroecological
      scales. 

PMID- 23874906
TI  - Elevational gradient in species richness pattern of epigaeic beetles and
      underlying mechanisms at east slope of Balang Mountain in southwestern China.
AB  - We report on the species richness patterns of epigaeic beetles (Coleoptera:
      Carabidae and Staphylinidae) along a subtropical elevational gradient of Balang
      Mountain, southwestern China. We tested the roles of environmental factors (e.g.
      temperature, area and litter cover) and direct biotic interactions (e.g. foods
      and antagonists) that shape elevational diversity gradients. Beetles were sampled
      at 19 sites using pitfall traps along the studied elevational gradient ranging
      from 1500 m-4000 m during the 2004 growing season. A total of 74416 specimens
      representing 260 species were recorded. Species richness of epigaeic beetles and
      two families showed unimodal patterns along the elevational gradient, peaking at
      mid-elevations (c. 2535 m), and the ranges of most beetle species were narrow
      along the gradient. The potential correlates of both species richness and
      environmental variables were examined using linear and second order polynomial
      regressions. The results showed that temperature, area and litter cover had
      strong explanatory power of beetle species richness for nearly all richness
      patterns, of beetles as a whole and of Carabidae and Staphylinidae, but the
      density of antagonists was associated with species richness of Carabidae only.
      Multiple regression analyses suggested that the three environmental factors
      combined contributed most to richness patterns for most taxa. The results suggest
      that environmental factors associated with temperature, area and habitat
      heterogeneity could account for most variation in richness pattern of epigaeic
      beetles. Additionally, the mid-elevation peaks and the small range size of most
      species indicate that conservation efforts should give attention to the entire
      gradient rather than just mid-elevations.

PMID- 23874907
TI  - Significant impact of the MTHFR polymorphisms and haplotypes on male infertility
      risk.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylene
      tetrahydrofolate to 5-methyl tetrahydrofolate and affects the activity of
      cellular cycles participating in nucleotide synthesis, DNA repair, genome
      stability, maintenance of methyl pool, and gene regulation. Genetically
      compromised MTHFR activity has been suggested to affect male fertility. The
      objective of the present study was to find the impact on infertility risk of
      c.203G>A, c.1298A>C, and c.1793G>A polymorphisms in the MTHFR gene. METHODS: PCR
      RFLP and DNA sequencing were used to genotype the common SNPs in the MTHFR gene
      in 630 infertile and 250 fertile males. Chi-square test was applied for
      statistical comparison of genotype data. Linkage disequilibrium between the SNPs
      and the frequency of common haplotypes were assessed using Haploview software.
      Biochemical levels of total homocysteine (tHcy) and folic acid were measured.
      Meta-analysis on c.1298A>C polymorphism was performed using data from ten
      studies, comprising 2734 cases and 2737 controls. RESULTS: c.203G>A and c.1298A>C
      were found to be unrelated to infertility risk. c.1793G>A was protective against
      infertility (P = 0.0008). c.677C>T and c.1793G>A were in significant LD (D' =
      0.9). Folic acid and tHcy level did not correlate with male infertility. Pooled
      estimate on c.1298A>C data from all published studies including our data showed
      no association of this polymorphism with male infertility (Odds ratio = 1.035, P
      = 0.56), azoospermia (Odds ratio = 0.97, P = 0.74), or
      oligoasthenoteratozoospermia (Odds ratio = 0.92, p = 0.29). Eight haplotypes with
      more than 1% frequency were detected, of which CCGA was protective against
      infertility (p = 0.02), but the significance of the latter was not seen after
      applying Bonferroni correction. CONCLUSION: Among MTHFR polymorphisms, c.203G>A
      and c.1298A>C do not affect infertility risk and c.1793G>A is protective against
      infertility. Haplotype analysis suggested that risk factors on the MTHFR locus do
      not extend too long on the DNA string.

PMID- 23874908
TI  - Metagenomic insights into metabolic capacities of the gut microbiota in a fungus
      cultivating termite (Odontotermes yunnanensis).
AB  - Macrotermitinae (fungus-cultivating termites) are major decomposers in tropical
      and subtropical areas of Asia and Africa. They have specifically evolved
      mutualistic associations with both a Termitomyces fungi on the nest and a gut
      microbiota, providing a model system for probing host-microbe interactions. Yet
      the symbiotic roles of gut microbes residing in its major feeding caste remain
      largely undefined. Here, by pyrosequencing the whole gut metagenome of adult
      workers of a fungus-cultivating termite (Odontotermes yunnanensis), we showed
      that it did harbor a broad set of genes or gene modules encoding carbohydrate
      active enzymes (CAZymes) relevant to plant fiber degradation, particularly
      debranching enzymes and oligosaccharide-processing enzymes. Besides, it also
      contained a considerable number of genes encoding chitinases and glycoprotein
      oligosaccharide-processing enzymes for fungal cell wall degradation. To
      investigate the metabolic divergence of higher termites of different feeding
      guilds, a SEED subsystem-based gene-centric comparative analysis of the data with
      that of a previously sequenced wood-feeding Nasutitermes hindgut microbiome was
      also attempted, revealing that SEED classifications of nitrogen metabolism, and
      motility and chemotaxis were significantly overrepresented in the wood-feeder
      hindgut metagenome, while Bacteroidales conjugative transposons and subsystems
      related to central aromatic compounds metabolism were apparently overrepresented
      here. This work fills up our gaps in understanding the functional capacities of
      fungus-cultivating termite gut microbiota, especially their roles in the
      symbiotic digestion of lignocelluloses and utilization of fungal biomass, both of
      which greatly add to existing understandings of this peculiar symbiosis. 

PMID- 23874909
TI  - Identifying issue frames in text.
AB  - Framing, the effect of context on cognitive processes, is a prominent topic of
      research in psychology and public opinion research. Research on framing has
      traditionally relied on controlled experiments and manually annotated document
      collections. In this paper we present a method that allows for quantifying the
      relative strengths of competing linguistic frames based on corpus analysis. This
      method requires little human intervention and can therefore be efficiently
      applied to large bodies of text. We demonstrate its effectiveness by tracking
      changes in the framing of terror over time and comparing the framing of abortion
      by Democrats and Republicans in the U.S. 

PMID- 23874910
TI  - Antizyme inhibitor 2 hypomorphic mice. New patterns of expression in pancreas and
      adrenal glands suggest a role in secretory processes.
AB  - The intracellular levels of polyamines, polycations implicated in proliferation,
      differentiation and cell survival, are regulated by controlling their
      biosynthesis, catabolism and transport. Antizymes and antizyme inhibitors are key
      regulatory proteins of polyamine levels by affecting ornithine decarboxylase, the
      rate-limiting biosynthetic enzyme, and polyamine uptake. We recently described
      the molecular function of a novel antizyme inhibitor (AZIN2). However, the
      physiological function of AZIN2 in mammals is mostly unknown. To gain insight on
      the tissue expression profile of AZIN2 and to find its possible physiological
      role, we have generated, transgenic mice with severe Azin2 hypomorphism. This
      mouse model expresses transgenic bacterial beta-D-galactosidase as a reporter
      gene, under the control of the Azin2 endogenous promoter, what allows a very
      sensitive and specific detection of the expression of the gene in the different
      tissues of transgenic mice. The biochemical and histochemical analyses of beta-D
      galactosidase together with the quantification of Azin2 mRNA levels, corroborated
      that AZIN2 is mainly expressed in testis and brain, and showed for the first time
      that AZIN2 is also expressed in the adrenal glands and pancreas. In these
      tissues, AZIN2 was not expressed in all type of cells, but rather in specific
      type of cells. Thus, AZIN2 was mainly found in the haploid germinal cells of the
      testis and in different brain regions such as hippocampus and cerebellum,
      particularly in specific type of neurons. In the adrenal glands and pancreas, the
      expression was restricted to the adrenal medulla and to the Langerhans islets,
      respectively. Interestingly, plasma insulin levels were significantly reduced in
      the transgenic mice. These results support the idea that AZIN2 may have a role in
      the modulation of reproductory and secretory functions and that this mouse model
      might be an interesting tool for the progress of our understanding on the role of
      AZIN2 and polyamines in specific mammalian cells. 

PMID- 23874911
TI  - The modified selenenyl amide, M-hydroxy ebselen, attenuates diabetic nephropathy
      and diabetes-associated atherosclerosis in ApoE/GPx1 double knockout mice.
AB  - Seleno-organic glutathione peroxidase (GPx) mimetics, including ebselen (Eb),
      have been tested in in vitro studies for their ability to scavenge reactive
      oxygen and nitrogen species, including hydrogen peroxide and peroxynitrite. In
      this study, we investigated the efficacies of two Eb analogues, m-hydroxy ebselen
      (ME) and ethanol-ebselen (EtE) and compared these with Eb in cell based assays.
      We found that ME is superior in attenuating the activation of hydrogen peroxide
      induced pro-inflammatory mediators, ERK and P38 in human aortic endothelial
      cells. Consequently, we investigated the effects of ME in an in vivo model of
      diabetes, the ApoE/GPx1 double knockout (dKO) mouse. We found that ME attenuates
      plaque formation in the aorta and lesion deposition within the aortic sinus of
      diabetic dKO mice. Oxidative stress as assessed by 8-OHdG in urine and
      nitrotyrosine immunostaining in the aortic sinus and kidney tubules, was reduced
      by ME in diabetic dKO mice. ME also attenuated diabetes-associated renal injury
      which included tubulointerstitial fibrosis and glomerulosclerosis. Furthermore,
      the bioactivity of the pro-fibrotic cytokine transforming growth factor-beta (TGF
      beta) as assessed by phospho-Smad2/3 immunostaining was attenuated after
      treatment with ME. TGF-beta-stimulated increases in collagen I and IV gene
      expression and protein levels were attenuated by ME in rat kidney tubular cells.
      However, in contrast to the superior activity of ME in in vitro and cell based
      assays, ME did not further augment the attenuation of diabetes-associated
      atherosclerosis and renal injury in our in vivo model when compared with Eb. In
      conclusion, this study strengthens the notion that bolstering GPx-like activity
      using synthetic mimetics may be a useful therapeutic strategy in lessening the
      burden of diabetic complications. However, these studies highlight the importance
      of in vivo analyses to test the efficacies of novel Eb analogues, as in vitro and
      cell based assays are only partly predictive of the in vivo situation. 

PMID- 23874912
TI  - Serine protease EspP from enterohemorrhagic Escherichia coli is sufficient to
      induce shiga toxin macropinocytosis in intestinal epithelium.
AB  - Life-threatening intestinal and systemic effects of the Shiga toxins produced by
      enterohemorrhagic Escherichia coli (EHEC) require toxin uptake and transcytosis
      across intestinal epithelial cells. We have recently demonstrated that EHEC
      infection of intestinal epithelial cells stimulates toxin macropinocytosis, an
      actin-dependent endocytic pathway. Host actin rearrangement necessary for EHEC
      attachment to enterocytes is mediated by the type 3 secretion system which
      functions as a molecular syringe to translocate bacterial effector proteins
      directly into host cells. Actin-dependent EHEC attachment also requires the outer
      membrane protein intimin, a major EHEC adhesin. Here, we investigate the role of
      type 3 secretion in actin turnover occurring during toxin macropinocytosis. Toxin
      macropinocytosis is independent of EHEC type 3 secretion and intimin attachment.
      EHEC soluble factors are sufficient to stimulate macropinocytosis and deliver
      toxin into enterocytes in vitro and in vivo; intact bacteria are not required.
      Intimin-negative enteroaggregative Escherichia coli (EAEC) O104:H4 robustly
      stimulate Shiga toxin macropinocytosis into intestinal epithelial cells. The
      apical macropinosomes formed in intestinal epithelial cells move through the
      cells and release their cargo at these cells' basolateral sides. Further analysis
      of EHEC secreted proteins shows that a serine protease EspP alone is able to
      stimulate host actin remodeling and toxin macropinocytosis. The observation that
      soluble factors, possibly serine proteases including EspP, from each of two
      genetically distinct toxin-producing strains, can stimulate Shiga toxin
      macropinocytosis and transcellular transcytosis alters current ideas concerning
      mechanisms whereby Shiga toxin interacts with human enterocytes. Mechanisms
      important for this macropinocytic pathway could suggest new potential therapeutic
      targets for Shiga toxin-induced disease. 

PMID- 23874913
TI  - Cardioprotective effects of a novel hydrogen sulfide agent-controlled release
      formulation of S-propargyl-cysteine on heart failure rats and molecular
      mechanisms.
AB  - OBJECTIVE: Heart failure (HF) is one of the most serious diseases worldwide. S
      propargyl-cysteine (SPRC), a novel modulator of endogenous hydrogen sulfide, is
      proved to be able to protect against acute myocardial ischemia. In order to
      produce more stable and sustainable hydrogen sulfide, we used controlled release
      formulation of SPRC (CR-SPRC) to elucidate possible cardioprotective effects on
      HF rats and investigate involved mechanisms on apoptosis and oxidation. METHODS:
      Left coronary artery was occluded to induce HF model of rat. The survival rats
      were randomly divided into 7 groups after 24 hours and treated with drugs for 6
      weeks. Echocardiographic indexes were recorded to determine cardiac function. TTC
      staining was performed to determine infarct size. Plasmatic level of hydrogen
      sulfide was detected by modified sulfide electrode. Activity of enzyme and
      expression of protein were determined by colorimetry and Western blot,
      respectively. RESULTS: The cardioprotective effects of CR-SPRC on HF rats were
      confirmed by significant reduction of infarct size and improvement of cardiac
      function, with better effects compared to normal SPRC. CR-SPRC modulated
      antioxidant defenses by preserving levels of GSH, CAT and SOD and reducing CK
      leakage. In addition, CR-SPRC elevated ratio of Bcl-2/Bax and inhibited activity
      of caspases to protect against myocardial apoptosis. The cardioprotective effects
      of CR-SPRC were mediated by hydrogen sulfide. CONCLUSIONS: All experiment data
      indicated cardioprotective effects of CR-SPRC on HF rats. More importantly, CR
      SPRC exerted better effects than normal SPRC in all respects, providing a new
      perspective on hydrogen sulfide-mediated drug therapy.

PMID- 23874914
TI  - When history repeats itself: exploring the genetic architecture of host-plant
      adaptation in two closely related lepidopteran species.
AB  - The genus Ostrinia includes two allopatric maize pests across Eurasia, namely the
      European corn borer (ECB, O. nubilalis) and the Asian corn borer (ACB, O.
      furnacalis). A third species, the Adzuki bean borer (ABB, O. scapulalis), occurs
      in sympatry with both the ECB and the ACB. The ABB mostly feeds on native dicots,
      which probably correspond to the ancestral host plant type for the genus
      Ostrinia. This situation offers the opportunity to characterize the two
      presumably independent adaptations or preadaptations to maize that occurred in
      the ECB and ACB. In the present study, we aimed at deciphering the genetic
      architecture of these two adaptations to maize, a monocot host plant recently
      introduced into Eurasia. To this end, we performed a genome scan analysis based
      on 684 AFLP markers in 12 populations of ECB, ACB and ABB. We detected 2 outlier
      AFLP loci when comparing French populations of the ECB and ABB, and 9 outliers
      when comparing Chinese populations of the ACB and ABB. These outliers were
      different in both countries, and we found no evidence of linkage disequilibrium
      between any two of them. These results suggest that adaptation or preadaptation
      to maize relies on a different genetic architecture in the ECB and ACB. However,
      this conclusion must be considered in light of the constraints inherent to genome
      scan approaches and of the intricate evolution of adaptation and reproductive
      isolation in the Ostrinia spp. complex. 

PMID- 23874915
TI  - Esophageal squamous cell carcinoma and gastric cardia adenocarcinoma shared
      susceptibility locus in PLCE1: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Two recent genome-wide association studies have
      identified a shared susceptibility variation PLCE1 rs2274223 for esophageal
      squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA).
      Subsequent case-control studies have reported this association in other
      populations. However, the findings were controversial and the effect remains
      undetermined. Our aim is to provide a precise quantification of the association
      between PLCE1 rs2274223 variation and the risk of ESCC and GCA. METHODS: Studies
      were identified by a literature search in MEDLINE and EMBASE databases. Pooled
      odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the
      association in allele, dominant, recessive, homozygous, and heterozygous models.
      RESULTS: Ten articles were identified, including 22156 ESCC cases and 28803
      controls, 5197 GCA cases and 17613 controls. Overall, PLCE1 rs2274223 G allele (G
      vs. A: OR=1.26, 95% CI: 1.15-1.39 for ESCC; OR=1.51, 95% CI: 1.35-1.69 for GCA)
      and its carrier (GG +AG vs. AA: OR = 1.23; 95% CI =1.02-1.49 for ESCC; OR =1.62;
      95% CI =1.15-2.29 for GCA) were significantly associated with the risk of ESCC
      and GCA. In stratified analysis by ethnicity, significant association of PLCE1
      rs2274223 G allele and the risk of ESCC (OR=1.33, 95% CI 1.21-1.45) and GCA (OR
      =1.56, 95% CI: 1.47-1.64) was observed in Chinese population. CONCLUSIONS: Our
      meta-analysis results indicated that PLCE1 rs2274223 G allele significantly
      contributed to the risk of ESCC and GCA, especially in Chinese population.

PMID- 23874916
TI  - Deletion of Snai2 and Snai3 results in impaired physical development compounded
      by lymphocyte deficiency.
AB  - The Snail family of transcriptional regulators consists of three highly conserved
      members. These proteins regulate (repress) transcription via the recruitment of
      histone deacetylases to target gene promoters that possess the appropriate E-box
      binding sequences. Murine Snai1 is required for mouse development while Snai2
      deficient animals survive with some anomalies. Less is known about the third
      member of the family, Snai3. To investigate the function of Snai3, we generated a
      conditional knockin mouse. Utilizing Cre-mediated deletion to facilitate the
      ablation of Snai3 in T cells or the entire animal, we found little to no effect
      of the loss of Snai3 in the entire animal or in T cell lineages. This finding
      provided the hypothesis that absence of Snai3 was mitigated, in part, by the
      presence of Snai2. To test this hypothesis we created Snai2/Snai3 double
      deficient mice. The developmental consequences of lacking both of these proteins
      was manifested in stunted growth, a paucity of offspring including a dramatic
      deficiency of female mice, and impaired immune cell development within the
      lymphoid lineages. 

PMID- 23874917
TI  - Reconstructing the timing and dispersion routes of HIV-1 subtype B epidemics in
      the Caribbean and Central America: a phylogenetic story.
AB  - The Caribbean and Central America are among the regions with highest HIV-1B
      prevalence worldwide. Despite of this high virus burden, little is known about
      the timing and the migration patterns of HIV-1B in these regions. Migration is
      one of the major processes shaping the genetic structure of virus populations.
      Thus, reconstruction of epidemiological network may contribute to understand HIV
      1B evolution and reduce virus prevalence. We have investigated the spatio
      temporal dynamics of the HIV-1B epidemic in The Caribbean and Central America
      using 1,610 HIV-1B partial pol sequences from 13 Caribbean and 5 Central American
      countries. Timing of HIV-1B introduction and virus evolutionary rates, as well as
      the spatial genetic structure of the HIV-1B populations and the virus migration
      patterns were inferred. Results revealed that in The Caribbean and Central
      America most of the HIV-1B variability was generated since the 80 s. At odds with
      previous data suggesting that Haiti was the origin of the epidemic in The
      Caribbean, our reconstruction indicated that the virus could have been
      disseminated from Puerto Rico and Antigua. These two countries connected two
      distinguishable migration areas corresponding to the (mainly Spanish-colonized)
      Easter and (mainly British-colonized) Western islands, which indicates that virus
      migration patterns are determined by geographical barriers and by the movement of
      human populations among culturally related countries. Similar factors shaped the
      migration of HIV-1B in Central America. The HIV-1B population was significantly
      structured according to the country of origin, and the genetic diversity in each
      country was associated with the virus prevalence in both regions, which suggests
      that virus populations evolve mainly through genetic drift. Thus, our work
      contributes to the understanding of HIV-1B evolution and dispersion pattern in
      the Americas, and its relationship with the geography of the area and the
      movements of human populations. 

PMID- 23874918
TI  - Nitrogen starvation induced oxidative stress in an oil-producing green alga
      Chlorella sorokiniana C3.
AB  - Microalgal lipid is one of the most promising feedstocks for biodiesel
      production. Chlorella appears to be a particularly good option, and nitrogen (N)
      starvation is an efficient environmental pressure used to increase lipid
      accumulation in Chlorella cells. The effects of N starvation of an oil-producing
      wild microalga, Chlorella sorokiniana C3, on lipid accumulation were investigated
      using thin layer chromatography (TLC), confocal laser scanning microscopy (CLSM)
      and flow cytometry (FCM). The results showed that N starvation resulted in lipid
      accumulation in C. sorokiniana C3 cells, oil droplet (OD) formation and
      significant lipid accumulation in cells were detected after 2 d and 8 d of N
      starvation, respectively. During OD formation, reduced photosynthetic rate,
      respiration rate and photochemistry efficiency accompanied by increased damage to
      PSII were observed, demonstrated by chlorophyll (Chl) fluorescence, 77K
      fluorescence and oxygen evolution tests. In the mean time the rate of cyclic
      electron transportation increased correspondingly to produce more ATP for
      triacylglycerols (TAGs) synthesis. And 0.5 d was found to be the turning point
      for the early stress response and acclimation of cells to N starvation. Increased
      level of membrane peroxidation was also observed during OD formation, and
      superoxide dismutase (SOD), peroxide dismutase (POD) and catalase (CAT) enzyme
      activity assays suggested impaired reactive oxygen species (ROS) scavenging
      ability. Significant neutral lipid accumulation was also observed by artificial
      oxidative stress induced by H2O2 treatment. These results suggested coupled
      neutral lipid accumulation and oxidative stress during N starvation in C.
      sorokiniana C3. 

PMID- 23874919
TI  - A linkage disequilibrium-based approach to selecting disease-associated rare
      variants.
AB  - Rare variants have increasingly been cited as major contributors in the disease
      etiology of several complex disorders. Recently, several approaches have been
      proposed for analyzing the association of rare variants with disease. These
      approaches include collapsing rare variants, summing rare variant test statistics
      within a particular locus to improve power, and selecting a subset of rare
      variants for association testing, e.g., the step-up approach. We found that (a)
      if the variants being pooled are in linkage disequilibrium, the standard step-up
      method of selecting the best subset of variants results in loss of power compared
      to a model that pools all rare variants and (b) if the variants are in linkage
      equilibrium, performing a subset selection using step-based selection methods
      results in a gain of power of association compared to a model that pools all rare
      variants. Therefore, we propose an approach to selecting the best subset of
      variants to include in the model that is based on the linkage disequilibrium
      pattern among the rare variants. The proposed linkage disequilibrium-based
      variant selection model is flexible and borrows strength from the model that
      pools all rare variants when the rare variants are in linkage disequilibrium and
      from step-based selection methods when the variants are in linkage equilibrium.
      We performed simulations under three different realistic scenarios based on: (1)
      the HapMap3 dataset of the DRD2 gene, and CHRNA3/A5/B4 gene cluster (2) the block
      structure of linkage disequilibrium, and (3) linkage equilibrium. We proposed a
      permutation-based approach to control the type 1 error rate. The power
      comparisons after controlling the type 1 error show that the proposed linkage
      disequilibrium-based subset selection approach is an attractive alternative
      method for subset selection of rare variants. 

PMID- 23874920
TI  - A pharmacological screening approach for discovery of neuroprotective compounds
      in ischemic stroke.
AB  - With the availability and ease of small molecule production and design continuing
      to improve, robust, high-throughput methods for screening are increasingly
      necessary to find pharmacologically relevant compounds amongst the masses of
      potential candidates. Here, we demonstrate that a primary oxygen glucose
      deprivation assay in primary cortical neurons followed by secondary assays (i.e.
      post-treatment protocol in organotypic hippocampal slice cultures and cortical
      neurons) can be used as a robust screen to identify neuroprotective compounds
      with potential therapeutic efficacy. In our screen about 50% of the compounds in
      a library of pharmacologically active compounds displayed some degree of
      neuroprotective activity if tested in a pre-treatment toxicity assay but just a
      few of these compounds, including Carbenoxolone, remained active when tested in a
      post-treatment protocol. When further examined, Carbenoxolone also led to a
      significant reduction in infarction size and neuronal damage in the ischemic
      penumbra when administered six hours post middle cerebral artery occlusion in
      rats. Pharmacological testing of Carbenoxolone-related compounds, acting by
      inhibition of 11-beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1), gave rise to
      similarly potent in vivo neuroprotection. This indicates that the increase of
      intracellular glucocorticoid levels mediated by 11beta-HSD1 may be involved in
      the mechanism that exacerbates ischemic neuronal cell death, and inhibiting this
      enzyme could have potential therapeutic value for neuroprotective therapies in
      ischemic stroke and other neurodegenerative disorders associated with neuronal
      injury. 

PMID- 23874921
TI  - Evolution of high tooth replacement rates in sauropod dinosaurs.
AB  - BACKGROUND: Tooth replacement rate can be calculated in extinct animals by
      counting incremental lines of deposition in tooth dentin. Calculating this rate
      in several taxa allows for the study of the evolution of tooth replacement rate.
      Sauropod dinosaurs, the largest terrestrial animals that ever evolved, exhibited
      a diversity of tooth sizes and shapes, but little is known about their tooth
      replacement rates. METHODOLOGY/PRINCIPAL FINDINGS: We present tooth replacement
      rate, formation time, crown volume, total dentition volume, and enamel thickness
      for two coexisting but distantly related and morphologically disparate sauropod
      dinosaurs Camarasaurus and Diplodocus. Individual tooth formation time was
      determined by counting daily incremental lines in dentin. Tooth replacement rate
      is calculated as the difference between the number of days recorded in successive
      replacement teeth. Each tooth family in Camarasaurus has a maximum of three
      replacement teeth, whereas each Diplodocus tooth family has up to five. Tooth
      formation times are about 1.7 times longer in Camarasaurus than in Diplodocus
      (315 vs. 185 days). Average tooth replacement rate in Camarasaurus is about one
      tooth every 62 days versus about one tooth every 35 days in Diplodocus. Despite
      slower tooth replacement rates in Camarasaurus, the volumetric rate of
      Camarasaurus tooth replacement is 10 times faster than in Diplodocus because of
      its substantially greater tooth volumes. A novel method to estimate replacement
      rate was developed and applied to several other sauropodomorphs that we were not
      able to thin section. CONCLUSIONS/SIGNIFICANCE: Differences in tooth replacement
      rate among sauropodomorphs likely reflect disparate feeding strategies and/or
      food choices, which would have facilitated the coexistence of these gigantic
      herbivores in one ecosystem. Early neosauropods are characterized by high tooth
      replacement rates (despite their large tooth size), and derived titanosaurs and
      diplodocoids independently evolved the highest known tooth replacement rates
      among archosaurs.

PMID- 23874922
TI  - Adaptation to pH and role of PacC in the rice blast fungus Magnaporthe oryzae.
AB  - Fungi are known to adapt to pH partly via specific activation of the Pal
      signaling pathway and subsequent gene regulation through the transcription factor
      PacC. The role of PacC in pathogenic fungi has been explored in few species, and
      each time its partaking in virulence has been found. We studied the impact of pH
      and the role of PacC in the biology of the rice pathogen Magnaporthe oryzae.
      Conidia formation and germination were affected by pH whereas fungal growth and
      appressorium formation were not. Growth in vitro and in planta was characterized
      by alkalinization and ammonia accumulation in the surrounding medium. Expression
      of the MoPACC gene increased when the fungus was placed under alkaline
      conditions. Except for MoPALF, expression of the MoPAL genes encoding the pH
      signaling components was not influenced by pH. Deletion of PACC caused a
      progressive loss in growth rate from pH 5 to pH 8, a loss in conidia production
      at pH 8 in vitro, a loss in regulation of the MoPALF gene, a decreased production
      of secreted lytic enzymes and a partial loss in virulence towards barley and
      rice. PacC therefore plays a significant role in M. oryzae's biology, and pH is
      revealed as one component at work during interaction between the fungus and its
      host plants. 

PMID- 23874923
TI  - Estimating the prevalence of opioid diversion by "doctor shoppers" in the United
      States.
AB  - BACKGROUND: Abuse of prescription opioid analgesics is a serious threat to public
      health, resulting in rising numbers of overdose deaths and admissions to
      emergency departments and treatment facilities. Absent adequate patient
      information systems, "doctor shopping" patients can obtain multiple opioid
      prescriptions for nonmedical use from different unknowing physicians. Our study
      estimates the prevalence of doctor shopping in the US and the amounts and types
      of opioids involved. METHODS AND FINDINGS: The sample included records for 146.1
      million opioid prescriptions dispensed during 2008 by 76% of US retail
      pharmacies. Prescriptions were linked to unique patients and weighted to estimate
      all prescriptions and patients in the nation. Finite mixture models were used to
      estimate different latent patient populations having different patterns of using
      prescribers. On average, patients in the extreme outlying population (0.7% of
      purchasers), presumed to be doctor shoppers, obtained 32 opioid prescriptions
      from 10 different prescribers. They bought 1.9% of all opioid prescriptions,
      constituting 4% of weighed amounts dispensed. CONCLUSIONS: Our data did not
      provide information to make a clinical diagnosis of individuals. Very few of
      these patients can be classified with certainty as diverting drugs for nonmedical
      purposes. However, even patients with legitimate medical need for opioids who use
      large numbers of prescribers may signal dangerously uncoordinated care. To close
      the information gap that makes doctor shopping and uncoordinated care possible,
      states have created prescription drug monitoring programs to collect records of
      scheduled drugs dispensed, but the majority of physicians do not access this
      information. To facilitate use by busy practitioners, most monitoring programs
      should improve access and response time, scan prescription data to flag
      suspicious purchasing patterns and alert physicians and pharmacists. Physicians
      could also prevent doctor shopping by adopting procedures to screen new patients
      for their risk of abuse and to monitor patients' adherence to prescribed
      treatments.

PMID- 23874924
TI  - Is the pathogenic ergot fungus a conditional defensive mutualist for its host
      grass?
AB  - It is well recognized, that outcomes of mutualistic plant-microorganism
      interactions are often context dependent and can range from mutualistic to
      antagonistic depending on conditions. Instead, seemingly pathogenic associations
      are generally considered only harmful to plants. The ergot fungus (Claviceps
      purpurea) is a common seed pathogen of grasses and cereals. Ergot sclerotia
      contain alkaloids which can cause severe toxicity in mammals when ingested, and
      thus the fungal infection might provide protection for the host plant against
      mammalian herbivores. Theoretically, the net effect of ergot infection would
      positively affect host seed set if the cost is not too high and the defensive
      effect is strong enough. According to our empirical data, this situation is
      plausible. First, we found no statistically significant seed loss in wild red
      fescue (Festuca rubra) inflorescences due to ergot infection, but the seed
      succession decreased along increasing number of sclerotia. Second, in a food
      choice experiment, sheep showed avoidance against forage containing ergot. Third,
      the frequency of ergot-infected inflorescences was higher in sheep pastures than
      surrounding ungrazed areas, indicating a protective effect against mammalian
      grazing. We conclude that, although ergot can primarily be categorized as a plant
      pathogen, ergot infection may sometimes represent indirect beneficial effects for
      the host plant. Ergot may thus serve as a conditional defensive mutualist for its
      host grass, and the pathogenic interaction may range from antagonistic to
      mutualistic depending on the situation. 

PMID- 23874925
TI  - Multidisciplinary modalities achieve encouraging long-term survival in resectable
      limited-disease esophageal small cell carcinoma.
AB  - BACKGROUND: The management of limited-disease esophageal small cell carcinoma is
      not well defined, and the role of surgery is still controversial. We aim to
      determine the optimal treatment strategy in limited-disease of esophageal small
      cell carcinoma. METHODS AND FINDINGS: We conducted a retrospective review of 141
      patients with limited-disease esophageal small cell carcinoma from 3 institutions
      in China who underwent treatment between July 1994 and September 2008, July 1994
      and July 2011, and June 2004 and December 2010, respectively. The survival rate
      was calculated by the Kaplan-Meier method, and the log-rank test was used to
      assess the survival differences between the groups. Cox proportional hazards
      model were used to further determine the independent factors impacting overall
      survival. The median survival time was 16.1 months for the entire cohort of
      patients, with a 5-year survival rate of 6.7%. The median survival times for
      surgery alone, surgery combined with chemotherapy, surgery combined with
      radiotherapy, surgery combined with chemotherapy and radiotherapy, chemotherapy
      plus radiotherapy, and chemotherapy alone were 18.0 months, 15.0 months, 23.0
      months, 25.0 months, 17.1 months, and 6.1 months, respectively; the corresponding
      5-year survival rates were 0%, 15.4%, 0%, 38.9%, 0%, and 0%, respectively. For
      the 105 patients who underwent R0 resection, the median disease-free survival
      time was 12.0 months, with a 95% confidence interval of 9.5 months to 14.5
      months. The multivariate Cox regression analysis demonstrated that advanced
      pathological staging (p = 0.003), and pure esophageal small cell carcinoma (p =
      0.035) were independent factors decreasing overall survival. CONCLUSIONS: Our
      data suggested that multidisciplinary modalities achieved encouraging long-term
      survival in patients with resectable limited-disease of esophageal small cell
      carcinoma.

PMID- 23874926
TI  - High cytoplasmic FOXO1 and pFOXO1 expression in astrocytomas are associated with
      worse surgical outcome.
AB  - FOXO1 is at a convergence point of receptor tyrosine kinase (RTK) signaling,
      which is one of the three core pathways implicated in glioblastoma. It was
      recently shown that FOXO1 can effectively induce glioma cell death and inhibit
      tumor growth through cell cycle arrest and apoptosis. We therefore evaluated
      FOXO1 and pFOXO1 protein expression in 181 primary astrocytoma samples and 16
      normal brain samples. Astrocytoma samples expressed higher cytoplasmic FOXO1 and
      pFOXO1 than normal brain samples. Nuclear pFOXO1 level was significantly higher
      than nuclear FOXO1 in astrocytomas. High cytoplasmic FOXO1 expression was
      associated with older onset age (P = 0.001) and higher WHO grade (P = 0.001). The
      trend was also observed between cytoplasmic pFOXO1 expression and WHO grade
      although not significant. Univariate survival analysis showed that both high
      cytoplasmic FOXO1 and pFOXO1 expression indicated a significantly shorter median
      overall survival and progression-free survival. Multivariate survival analysis
      revealed cytoplasmic FOXO1 expression, cytoplasmic pFOXO1 expression, WHO grade,
      gender, extent of resection and radiotherapy to be independent prognostic factors
      for overall survival and progression-free survival. Thus, our data suggested that
      cytoplasmic FOXO1 and pFOXO1 expression may serve as valuable prognostic
      variables in astrocytomas and may have significant implications for the
      development and application of targeted therapy. 

PMID- 23874927
TI  - Extensive modulation of the transcription factor transcriptome during somatic
      embryogenesis in Arabidopsis thaliana.
AB  - Molecular mechanisms controlling plant totipotency are largely unknown and
      studies on somatic embryogenesis (SE), the process through which already
      differentiated cells reverse their developmental program and become embryogenic,
      provide a unique means for deciphering molecular mechanisms controlling
      developmental plasticity of somatic cells. Among various factors essential for
      embryogenic transition of somatic cells transcription factors (TFs), crucial
      regulators of genetic programs, are believed to play a central role. Herein, we
      used quantitative real-time polymerase chain reaction (qRT-PCR) to identify TF
      genes affected during SE induced by in vitro culture in Arabidopsis thaliana.
      Expression profiles of 1,880 TFs were evaluated in the highly embryogenic Col-0
      accession and the non-embryogenic tanmei/emb2757 mutant. Our study revealed 729
      TFs whose expression changes during the 10-days incubation period of SE; 141 TFs
      displayed distinct differences in expression patterns in embryogenic versus non
      embryogenic cultures. The embryo-induction stage of SE occurring during the first
      5 days of culture was associated with a robust and dramatic change of the TF
      transcriptome characterized by the drastic up-regulation of the expression of a
      great majority (over 80%) of the TFs active during embryogenic culture. In
      contrast to SE induction, the advanced stage of embryo formation showed
      attenuation and stabilization of transcript levels of many TFs. In total, 519 of
      the SE-modulated TFs were functionally annotated and transcripts related with
      plant development, phytohormones and stress responses were found to be most
      abundant. The involvement of selected TFs in SE was verified using T-DNA
      insertion lines and a significantly reduced embryogenic response was found for
      the majority of them. This study provides comprehensive data focused on the
      expression of TF genes during SE and suggests directions for further research on
      functional genomics of SE. 

PMID- 23874928
TI  - Sensitive assessment of the virologic outcomes of stopping and restarting non
      nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.
AB  - BACKGROUND: Non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant
      mutants have been shown to emerge after interruption of suppressive NNRTI-based
      antiretroviral therapy (ART) using routine testing. The aim of this study was to
      quantify the risk of resistance by sensitive testing and correlate the detection
      of resistance with NNRTI concentrations after treatment interruption and
      virologic responses after treatment resumption. METHODS: Resistance-associated
      mutations (RAMs) and NNRTI concentrations were studied in plasma from 132
      patients who interrupted suppressive ART within SMART. RAMs were detected by
      Sanger sequencing, allele-specific PCR, and ultra-deep sequencing. NNRTI
      concentrations were measured by sensitive high-performance liquid chromatography.
      RESULTS: Four weeks after NNRTI interruption, 19/31 (61.3%) and 34/39 (87.2%)
      patients showed measurable nevirapine (>0.25 ng/ml) or efavirenz (>5 ng/ml)
      concentrations, respectively. Median eight weeks after interruption, 22/131
      (16.8%) patients showed >=1 NNRTI-RAM, including eight patients with NNRTI-RAMs
      detected only by sensitive testing. The adjusted odds ratio (OR) of NNRTI-RAM
      detection was 7.62 (95% confidence interval [CI] 1.52, 38.30; p = 0.01) with
      nevirapine or efavirenz concentrations above vs. below the median measured in the
      study population. Staggered interruption, whereby nucleos(t)ide reverse
      transcriptase inhibitors (NRTIs) were continued for median nine days after NNRTI
      interruption, did not prevent NNRTI-RAMs, but increased detection of NRTI-RAMs
      (OR 4.25; 95% CI 1.02, 17.77; p = 0.03). After restarting NNRTI-based ART (n =
      90), virologic suppression rates <400 copies/ml were 8/13 (61.5%) with NNRTI
      RAMs, 7/11 (63.6%) with NRTI-RAMs only, and 51/59 (86.4%) without RAMs. The ORs
      of re-suppression were 0.18 (95% CI 0.03, 0.89) and 0.17 (95% CI 0.03, 1.15) for
      patients with NNRTI-RAMs or NRTI-RAMs only respectively vs. those without RAMs (p
      = 0.04). CONCLUSIONS: Detection of resistant mutants in the rebound viremia after
      interruption of efavirenz- or nevirapine-based ART affects outcomes once these
      drugs are restarted. Further studies are needed to determine RAM persistence in
      untreated patients and impact on newer NNRTIs.

PMID- 23874929
TI  - Volatile emissions from compressed tissue.
AB  - Since almost every fifth patient treated in hospital care develops pressure
      ulcers, early identification of risk is important. A non-invasive method for the
      elucidation of endogenous biomarkers related to pressure ulcers could be an
      excellent tool for this purpose. We therefore found it of interest to determine
      if there is a difference in the emissions of volatiles from compressed and
      uncompressed tissue. The ultimate goal is to find a non-invasive method to obtain
      an early warning for the risk of developing pressure ulcers for bed-ridden
      persons. Chemical analysis of the emissions, collected in compresses, was made
      with gas-chromatography-mass spectrometry and with a chemical sensor array, the
      so called electronic nose. It was found that the emissions from healthy and
      hospitalized persons differed significantly irrespective of the site. Within each
      group there was a clear difference between the compressed and uncompressed site.
      Peaks that could be certainly deemed as markers of the compression were, however,
      not identified. Nonetheless, different compounds connected to the application of
      local mechanical pressure were found. The results obtained with GC-MS reveal the
      complexity of VOC composition, thus an array of non-selective chemical sensors
      seems to be a suitable choice for the analysis of skin emission from compressed
      tissues; it may represent a practical instrument for bed side diagnostics.
      Results show that the adopted electronic noses are likely sensitive to the total
      amount of the emission rather than to its composition. The development of a gas
      sensor-based device requires then the design of sensor receptors adequate to
      detect the VOCs bouquet typical of pressure. This preliminary experiment
      evidences the necessity of studies where each given person is followed for a long
      time in a ward in order to detect the insurgence of specific VOCs pattern changes
      signalling the occurrence of ulcers.

PMID- 23874930
TI  - Cluster J mycobacteriophages: intron splicing in capsid and tail genes.
AB  - Bacteriophages isolated on Mycobacterium smegmatis mc(2)155 represent many
      distinct genomes sharing little or no DNA sequence similarity. The genomes are
      architecturally mosaic and are replete with genes of unknown function. A new
      group of genomes sharing substantial nucleotide sequences constitute Cluster J.
      The six mycobacteriophages forming Cluster J are morphologically members of the
      Siphoviridae, but have unusually long genomes ranging from 106.3 to 117 kbp.
      Reconstruction of the capsid by cryo-electron microscopy of mycobacteriophage
      BAKA reveals an icosahedral structure with a triangulation number of 13. All six
      phages are temperate and homoimmune, and prophage establishment involves
      integration into a tRNA-Leu gene not previously identified as a mycobacterial
      attB site for phage integration. The Cluster J genomes provide two examples of
      intron splicing within the virion structural genes, one in a major capsid subunit
      gene, and one in a tail gene. These genomes also contain numerous free-standing
      HNH homing endonuclease, and comparative analysis reveals how these could
      contribute to genome mosaicism. The unusual Cluster J genomes provide new
      insights into phage genome architecture, gene function, capsid structure, gene
      mobility, intron splicing, and evolution. 

PMID- 23874931
TI  - HIV-1 autologous antibody neutralization associates with mother to child
      transmission.
AB  - The HIV-1 characteristics associated with mother to child transmission (MTCT) are
      still poorly understood and if known would indicate where intervention strategies
      should be targeted. In contrast to horizontally infected individuals, exposed
      infants possess inherited antibodies (Abs) from their mother with the potential
      to protect against infection. We investigated the HIV-1 gp160 envelope proteins
      from seven transmitting mothers (TM) whose children were infected either during
      gestation or soon after delivery and from four non-transmitting mothers (NTM)
      with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested
      gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions,
      DC-SIGN capture and transfer and neutralization with an array of common
      neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant
      plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find
      differences in neutralization with the panel of NAbs. We did, however, find that
      TM possessed significantly higher plasma neutralization capacities than NTM (P =
      0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization
      capacity than mothers transmitting either peri - partum (PP) or via breastfeeding
      (BF) (P = 0.002). Plasma from children infected IU neutralized viruses carrying
      autologous gp160 viral envelopes as well as those from their corresponding
      mothers whilst plasma from children infected PP and/or BF demonstrated poor
      neutralizing capacity. Our results demonstrate heightened autologous NAb
      responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and
      more specifically in those infants infected IU. Although the number of HIV-1
      transmitting pairs is low our results indicate that autologous NAb responses in
      mothers and infants do not protect against MTCT and may in fact be detrimental
      when considering IU HIV-1 transmissions. 

PMID- 23874932
TI  - Evolutionary patterns of bone histology and bone compactness in xenarthran mammal
      long bones.
AB  - Bone microstructure reflects physiological characteristics and has been shown to
      contain phylogenetic and ecological signals. Although mammalian long bone
      histology is receiving increasing attention, systematic examination of the main
      clades has not yet been performed. Here we describe the long bone microstructure
      of Xenarthra based on thin sections representing twenty-two species.
      Additionally, patterns in bone compactness of humeri and femora are investigated.
      The primary bone tissue of xenarthran long bones is composed of a mixture of
      woven, parallel-fibered and lamellar bone. The vascular canals have a
      longitudinal, reticular or radial orientation and are mostly arranged in an
      irregular manner. Concentric rows of vascular canals and laminar organization of
      the tissue are only found in anteater bones. The long bones of adult specimens
      are marked by dense Haversian bone, a feature that has been noted for most groups
      of mammals. In the long bones of armadillos, secondary osteons have an oblique
      orientation within the three-dimensional bone tissue, thus resulting in their
      irregular shape when the bones are sectioned transversely. Secondary remodeling
      is generally more extensive in large taxa than in small taxa, and this could be
      caused by increased loading. Lines of arrested growth are assumed to be present
      in all specimens, but they are restricted to the outermost layer in bones of
      armadillos and are often masked by secondary remodeling in large taxa. Parameters
      of bone compactness show a pattern in the femur that separates Cingulata and
      Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness
      than pilosans. In addition, cingulates show an allometric relationship between
      humeral and femoral bone compactness. 

PMID- 23874933
TI  - Multimechanistic antifibrotic effect of biochanin a in rats: implications of
      proinflammatory and profibrogenic mediators.
AB  - OBJECTIVE: Biochanin A (BCA) is an isoflavone found in red clover and peanuts.
      Recently, it drew much attention as a promising anticancer and antioxidant. Due
      to its diversity in pharmacological actions, we were encouraged to investigate
      its potential as an antifibrotic, elucidating the different molecular mechanisms
      involved. DESIGN: Rats were pretreated with BCA, then injected with carbon
      tetrachloride (CCl4) for 6 weeks. Changes in liver weight and histology were
      examined and levels of aspartate and alanine aminotransferases, cholesterol,
      triglycerides, alkaline phosphatase and total bilirubin measured. To assess
      hepatic efficiency, indocyanine green was injected and its clearance calculated
      and albumin, total proteins and insulin-like growth factor-1 expression were
      measured. Cytochrome P4502E1 activity, cytochrome P4501A1 expression, in addition
      to sulfotransferase1A1 expression were determined to deduce the effect of BCA on
      hepatic metabolism. As oxidative stress markers, lipid peroxides levels, reduced
      glutathione, superoxide dismutase and catalase activities, as well as the total
      antioxidant capacity, were assessed. Nitric oxide, inducible nitric oxide
      synthase and cyclooxygenase-2 were used as indicators of the inflammatory
      response. Signaling pathways involving tumor necrosis factor-alpha, nuclear
      factor-kappa B, transforming growth factor-beta1, matrix metalloproteinase-9 and
      alpha-smooth muscle actin were investigated accordingly. Extent of fibrosis was
      examined by Masson's stain and measuring hydroxyproline levels. RESULTS: BCA
      pretreatment significantly protected against the chronic damage of CCl4. Liver
      injury, oxidative stress, inflammation and fibrosis markers decreased, while
      hepatic efficiency improved. CONCLUSION: Our findings suggested that BCA
      administration protects against fibrotic complications, a property that can be
      contributed to the multimechanistic approach of the drug.

PMID- 23874934
TI  - Acorn consumption improves the immune response of the dung beetle Thorectes
      lusitanicus.
AB  - Thorectes lusitanicus, a typically coprophagous species is also actively
      attracted to oak acorns, consuming, burying them, and conferring ecophysiological
      and reproductive advantages to both the beetle and the tree. In this study, we
      explored the possible relation between diet shift and the health status of T.
      lusitanicus using a generalist entomopathogenic fungus (Metarhizium anisopliae)
      as a natural pathogen. To measure the health condition and immune response of
      beetles, we analysed the protein content in the haemolymph, prophenoloxidase
      (proPO) content, phenoloxidase (PO) activity and mortality of beetles with diets
      based on either acorns or cow dung. Protein content, proPO levels and PO levels
      in the haemolymph of T. lusitanicus were found to be dependent on the type of
      diet. Furthermore, the beetles fed with acorns developed a more effective proPO
      PO system than the beetles fed with cow dung. Furthermore, a significant decrease
      in mortality was observed when infected individuals were submitted to an acorn
      based diet. In addition to enhancing an understanding of the relevance of dietary
      change to the evolutionary biology of dung beetles, these results provide a more
      general understanding of the ecophysiological implications of differential
      dietary selection in the context of fitness. 

PMID- 23874935
TI  - The importance of encoding-related neural dynamics in the prediction of inter
      individual differences in verbal working memory performance.
AB  - Studies of brain-behaviour interactions in the field of working memory (WM) have
      associated WM success with activation of a fronto-parietal network during the
      maintenance stage, and this mainly for visuo-spatial WM. Using an inter
      individual differences approach, we demonstrate here the equal importance of
      neural dynamics during the encoding stage, and this in the context of verbal WM
      tasks which are characterized by encoding phases of long duration and sustained
      attentional demands. Participants encoded and maintained 5-word lists, half of
      them containing an unexpected word intended to disturb WM encoding and associated
      task-related attention processes. We observed that inter-individual differences
      in WM performance for lists containing disturbing stimuli were related to
      activation levels in a region previously associated with task-related attentional
      processing, the left intraparietal sulcus (IPS), and this during stimulus
      encoding but not maintenance; functional connectivity strength between the left
      IPS and lateral prefrontal cortex (PFC) further predicted WM performance. This
      study highlights the critical role, during WM encoding, of neural substrates
      involved in task-related attentional processes for predicting inter-individual
      differences in verbal WM performance, and, more generally, provides support for
      attention-based models of WM. 

PMID- 23874936
TI  - New developments and applications of the MP2RAGE sequence--focusing the contrast
      and high spatial resolution R1 mapping.
AB  - MR structural T1-weighted imaging using high field systems (>3T) is severely
      hampered by the existing large transmit field inhomogeneities. New sequences have
      been developed to better cope with such nuisances. In this work we show the
      potential of a recently proposed sequence, the MP2RAGE, to obtain improved grey
      white matter contrast with respect to conventional T1-w protocols, allowing for a
      better visualization of thalamic nuclei and different white matter bundles in the
      brain stem. Furthermore, the possibility to obtain high spatial resolution (0.65
      mm isotropic) R1 maps fully independent of the transmit field inhomogeneities in
      clinical acceptable time is demonstrated. In this high resolution R1 maps it was
      possible to clearly observe varying properties of cortical grey matter throughout
      the cortex and observe different hippocampus fields with variations of intensity
      that correlate with known myelin concentration variations. 

PMID- 23874937
TI  - Ca2+-activated Cl- channels of the ClCa family express in the cilia of a subset
      of rat olfactory sensory neurons.
AB  - The Ca(2+)-activated Cl(-) channel is considered a key constituent of odor
      transduction. Odorant binding to a specific receptor in the cilia of olfactory
      sensory neurons (OSNs) triggers a cAMP cascade that mediates the opening of a
      cationic cyclic nucleotide-gated channel (CNG), allowing Ca(2+) influx. Ca(2+)
      ions activate Cl(-) channels, generating a significant Cl(-) efflux, with a large
      contribution to the receptor potential. The Anoctamin 2 channel (ANO2) is a major
      constituent of the Cl(-) conductance, but its knock-out has no impairment of
      behavior and only slightly reduces field potential odorant responses of the
      olfactory epithelium. Likely, an additional Ca(2+)-activated Cl(-) channel of
      unknown molecular identity is also involved. In addition to ANO2, we detected two
      members of the ClCa family of Ca(2+)-activated Cl(-) channels in the rat
      olfactory epithelium, ClCa4l and ClCa2. These channels, also expressed in the
      central nervous system, may correspond to odorant transduction channels. Whole
      Sprague Dawley olfactory epithelium nested RT-PCR and single OSNs established
      that the mRNAs of both channels are expressed in OSNs. Real time RT-PCR and full
      length sequencing of amplified ClCa expressed in rat olfactory epithelium
      indicated that ClCa4l is the most abundant. Immunoblotting with an antibody
      recognizing both channels revealed immunoreactivity in the ciliary membrane.
      Immunochemistry of olfactory epithelium and OSNs confirmed their ciliary presence
      in a subset of olfactory sensory neurons. The evidence suggests that ClCa4l and
      ClCa2 might play a role in odorant transduction in rat olfactory cilia. 

PMID- 23874938
TI  - Waist-to-height ratio and cardiovascular risk factors among Chinese adults in
      Beijing.
AB  - OBJECTIVES: To examine whether waist-to-height ratio (WHtR) performed better
      than, body mass index (BMI) or waist circumference (WC) in relation to
      hypertension, diabetes, and dyslipidemia among Chinese adults in Beijing.
      METHODS: A total of 5720 adults (2371 men and 3349 nonpregnant women) aged 18 to
      79 years were selected from the general population in a cross-sectional study.
      Data from a standardized questionnaire, physical examination, and blood sample
      were obtained. RESULTS: The area under curve (AUC) values for WHtR (0.661-0.773)
      were significantly higher than those for BMI for all outcomes in both sexes,
      except that WHtR and BMI had similar AUCs for dyslipidemia in men. The AUCs for
      WHtR were significantly higher than those for WC with respect to hypertension in
      both sexes, and to diabetes in women. AUCs for the relationships between
      anthropometric indices and the three outcomes were larger in women than in men,
      and tended to decrease with age. Optimal cutoffs for WHtR were 0.51-0.53 and 0.48
      0.50 in men and women, respectively. With regard to the current Chinese criteria
      for BMI (>= 24 kg/m(2)), WC (>= 90 cm for men, and >= 85 cm for women), and the
      recommended cutoff of WHtR (>= 0.5), WHtR yielded the greatest odds ratio for
      hypertension and diabetes in both sexes, and dyslipidemia in women. BMI had the
      highest odds ratio for dyslipidemia in men. The odds ratios of anthropometric
      indices for hypertension and diabetes, but not for dyslipidemia, were higher in
      women than in men. The association between anthropometric indices and the three
      outcomes decreased with age. CONCLUSION: WHtR performed better than BMI and WC
      for the association with hypertension and diabetes. More studies should be
      conducted to explore the age differences in the relationships between obesity
      indices and cardiovascular risk factors.

PMID- 23874939
TI  - Tyrosine Y189 in the substrate domain of the adhesion docking protein NEDD9 is
      conserved with p130Cas Y253 and regulates NEDD9-mediated migration and focal
      adhesion dynamics.
AB  - The focal adhesion docking protein NEDD9/HEF1/Cas-L regulates cell migration and
      cancer invasion. NEDD9 is a member of the Cas family of proteins that share
      conserved overall protein-protein interaction domain structure, including a
      substrate domain that is characterized by extensive tyrosine (Y) phosphorylation.
      Previous studies have suggested that phosphorylation of Y253 in the substrate
      domain of the Cas family protein p130Cas is specifically required for p130Cas
      function in cell migration. While it is clear that tyrosine phosphorylation of
      the NEDD9 substrate domain is similarly required for the regulation of cell
      motility, whether individual NEDD9 tyrosine residues have discrete function in
      regulating motility has not previously been reported. In the present study we
      have used a global sequence alignment of Cas family proteins to identify a
      putative NEDD9 equivalent of p130Cas Y253. We find that NEDD9 Y189 aligns with
      p130Cas Y253 and that it is conserved among NEDD9 vertebrate orthologues.
      Expression of NEDD9 in which Y189 is mutated to phenylalanine results in
      increased rates of cell migration and is correlated with increased disassembly of
      GFP.NEDD9 focal adhesions. Conversely, mutation to Y189D significantly inhibits
      cell migration. Our previous data has suggested that NEDD9 stabilizes focal
      adhesions and the present data therefore suggests that phosphorylation of Y189
      NEDD9 is required for this function. These findings indicate that the individual
      tyrosine residues of the NEDD9 substrate domain may serve discrete functional
      roles. Given the important role of this protein in promoting cancer invasion,
      greater understanding of the function of the individual tyrosine residues is
      important for the future design of approaches to target NEDD9 to arrest cancer
      cell invasion. 

PMID- 23874940
TI  - Genetics and evolution of the Salmonella galactose-initiated set of o antigens.
AB  - This paper covers eight Salmonella serogroups, that are defined by O antigens
      with related structures and gene clusters. They include the serovars that are now
      most frequently isolated. Serogroups A, B1, B2, C2-C3, D1, D2, D3 and E have O
      antigens that are distinguished by having galactose as first sugar, and not N
      acetyl glucosamine or N-acetyl galactosamine as in the other 38 serogroups, and
      indeed in most Enterobacteriaceae. The gene clusters for these galactose
      initiated appear to have entered S. enterica since its divergence from E. coli,
      but sequence comparisons show that much of the diversification occurred long
      before this. We conclude that the gene clusters must have entered S. enterica in
      a series of parallel events. The individual gene clusters are discussed, followed
      by analysis of the divergence for those genes shared by two or more gene
      clusters, and a putative phylogenic tree for the gene clusters is presented. This
      set of O antigens provides a rare case where it is possible to examine in detail
      the relationships of a significant number of O antigens. In contrast the more
      common pattern of O-antigen diversity within a species is for there to be only a
      few cases of strains having related gene clusters, suggesting that diversity
      arose through gain of individual O-antigen gene clusters by lateral gene
      transfer, and under these circumstances the evolution of the diversity is not
      accessible. This paper on the galactose-initiated set of gene clusters gives new
      insights into the origins of O-antigen diversity generally. 

PMID- 23874941
TI  - Inter-physician variation in follow-up colonoscopies after screening colonoscopy.
AB  - BACKGROUND AND AIMS: Surveillance is an integral part of the colorectal cancer
      (CRC) screening process. We aimed to investigate inter-physician variation in
      follow-up procedures after screening colonoscopy in an opportunistic CRC
      screening program. METHODS: A historical cohort study in the German statutory
      health insurance system was conducted. 55,301 individuals who underwent screening
      colonoscopy in 2006 in Bavaria, Germany, and who were not diagnosed with CRC were
      included. Utilization of follow-up colonoscopies performed by the same physician
      (328 physicians overall) within 3 years was ascertained. Mixed effects logistic
      regression modelling was used to assess the effect of physicians and other
      potential predictors (screening result, age group, and sex) on re-utilization of
      colonoscopy. Physicians were grouped into quintiles according to individual
      effects estimated in a preliminary model. Predicted probabilities of follow-up
      colonoscopy by screening result and physician group were calculated. RESULTS: The
      observed rate of follow-up colonoscopy was 6.2% (95% confidence interval: 5.9
      6.4%), 18.6% (17.8-19.4%), and 37.0% (35.5-38.4%) after negative colonoscopy, low
      risk adenoma and high-risk adenoma detection, respectively. All considered
      predictors were statistically significantly associated with follow-up
      colonoscopy. The predicted probabilities of follow-up colonoscopy ranged from
      1.7% (1.4-2.0%) to 11.0% (10.2-11.7%), from 7.3% (6.2-8.5%) to 35.1% (32.6
      37.7%), and from 17.9% (15.5-20.6%) to 56.9% (53.5-60.3%) in the 1(st) quintile
      (lowest rates of follow-up) and 5(th) quintile (highest rates of follow-up) of
      physicians after negative colonoscopy, low-risk adenoma and high-risk adenoma
      detection, respectively. CONCLUSIONS: This study suggests substantial inter
      physician variation in follow-up habits after screening colonoscopy.
      Interventions, including organizational changes in CRC screening should be
      considered to reduce this variation.

PMID- 23874942
TI  - Phage p1-derived artificial chromosomes facilitate heterologous expression of the
      FK506 gene cluster.
AB  - We describe a procedure for the conjugative transfer of phage P1-derived
      Artificial Chromosome (PAC) library clones containing large natural product gene
      clusters (>=70 kilobases) to Streptomyces coelicolor strains that have been
      engineered for improved heterologous production of natural products. This
      approach is demonstrated using the gene cluster for FK506 (tacrolimus), a
      clinically important immunosuppressant of high commercial value. The entire 83.5
      kb FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488 present in one
      130 kb PAC clone was introduced into four different S. coelicolor derivatives and
      all produced FK506 and smaller amounts of the related compound FK520. FK506
      yields were increased by approximately five-fold (from 1.2 mg L(-1) to 5.5 mg L(
      1)) in S. coelicolor M1146 containing the FK506 PAC upon over-expression of the
      FK506 LuxR regulatory gene fkbN. The PAC-based gene cluster conjugation
      methodology described here provides a tractable means to evaluate and manipulate
      FK506 biosynthesis and is readily applicable to other large gene clusters
      encoding natural products of interest to medicine, agriculture and biotechnology.

PMID- 23874943
TI  - A modified entropy-based approach for identifying gene-gene interactions in case
      control study.
AB  - Gene-gene interactions may play an important role in the genetics of a complex
      disease. Detection and characterization of gene-gene interactions is a
      challenging issue that has stimulated the development of various statistical
      methods to address it. In this study, we introduce a method to measure gene
      interactions using entropy-based statistics from a contingency table of trait and
      genotype combinations. We also developed an exploration procedure by using
      graphs. We propose a standardized relative information gain (RIG) measure to
      evaluate the interactions between single nucleotide polymorphism (SNP)
      combinations. To identify the k (th) order interactions, contingency tables of
      trait and genotype combinations of k SNPs are constructed, with which RIGs are
      calculated. The RIGs are standardized using the mean and standard deviation from
      the permuted datasets. SNP combinations yielding high standardized RIG are chosen
      for gene-gene interactions. Detection of high-order interactions and comparison
      of interaction strengths between different orders are made possible by using
      standardized RIG. We have applied the proposed standardized entropy-based method
      to two types of data sets from a simulation study and a real genetic association
      study. We have compared our method and the multifactor dimensionality reduction
      (MDR) method through power analysis of eight different genetic models with
      varying penetrance rates, number of SNPs, and sample sizes. Our method shows
      successful identification of genetic associations and gene-gene interactions both
      in simulation and real genetic data. Simulation results suggest that the proposed
      entropy-based method is better able to detect high-order interactions and is
      superior to the MDR method in most cases. The proposed method is well suited for
      detecting interactions without main effects as well as for models including main
      effects. 

PMID- 23874944
TI  - Quantifying spatial variability of selected soil trace elements and their scaling
      relationships using multifractal techniques.
AB  - Multifractal techniques were utilized to quantify the spatial variability of
      selected soil trace elements and their scaling relationships in a 10.24-ha
      agricultural field in northeast China. 1024 soil samples were collected from the
      field and available Fe, Mn, Cu and Zn were measured in each sample. Descriptive
      results showed that Mn deficiencies were widespread throughout the field while Fe
      and Zn deficiencies tended to occur in patches. By estimating single multifractal
      spectra, we found that available Fe, Cu and Zn in the study soils exhibited high
      spatial variability and the existence of anomalies ([alpha(q)max
      alpha(q)min]>=0.54), whereas available Mn had a relatively uniform distribution
      ([alpha(q)max-alpha(q)min]~0.10). The joint multifractal spectra revealed that
      the strong positive relationships (r>=0.86, P<0.001) among available Fe, Cu and
      Zn were all valid across a wider range of scales and over the full range of data
      values, whereas available Mn was weakly related to available Fe and Zn (r>=0.18,
      P<0.01) but not related to available Cu (r = -0.03, P = 0.40). These results show
      that the variability and singularities of selected soil trace elements as well as
      their scaling relationships can be characterized by single and joint multifractal
      parameters. The findings presented in this study could be extended to predict
      selected soil trace elements at larger regional scales with the aid of geographic
      information systems. 

PMID- 23874945
TI  - Breeding biology and variable mating system of a population of introduced
      dunnocks (Prunella modularis) in New Zealand.
AB  - Species with variable mating systems provide a unique opportunity to investigate
      whether females receive direct fitness benefits from additional male partners.
      The direct benefits provide an obvious explanation for why females would breed
      polyandrously, in a situation where males clearly do not attain their optimal
      reproductive success. Evidence for these direct benefits is, however, mixed.
      Here, we present a detailed study of the breeding biology of the dunnock,
      Prunella modularis, which inform an investigation into the effects of the social
      mating system on the reproductive success in a population of dunnocks in Southern
      New Zealand. We studied 80 different social groups over the course of three
      breeding seasons. Dunnocks in our population presented a variable mating system,
      with socially monogamous (45%), socially polyandrous (54%) and socially
      polygynandrous (1%) groups being observed in the same breeding season. We did not
      observe any polygynous social units in our study period although polygyny exists
      in the population. We found little difference in the numbers of eggs laid, and
      egg volume between monogamous and polyandrous nests. However, polyandrous groups
      had better hatching and fledging success than monogamous groups (composite d =
      0.385, 95% CI: 0.307 to 0.463). Overall our results support the notion that
      polyandry is beneficial for females. 

PMID- 23874946
TI  - Fgf21 impairs adipocyte insulin sensitivity in mice fed a low-carbohydrate, high
      fat ketogenic diet.
AB  - BACKGROUND: A low-carbohydrate, high-fat ketogenic diet (KD) induces hepatic
      ketogenesis and is believed to affect energy metabolism in mice. As hepatic Fgf21
      expression was markedly induced in mice fed KD, we examined the effects of KD
      feeding on metabolism and the roles of Fgf21 in metabolism in mice fed KD using
      Fgf21 knockout mice. METHODOLOGY/PRINCIPAL FINDINGS: We examined C57BL/6 mice fed
      KD for 6 or 14 days. Blood beta-hydroxybutyrate levels were greatly increased at
      6 days, indicating that hepatic ketogenesis was induced effectively by KD feeding
      for 6 days. KD feeding for 6 and 14 days impaired glucose tolerance and insulin
      sensitivity, although it did not affect body weight, blood NEFA, and triglyceride
      levels. Hepatic Fgf21 expression and blood Fgf21 levels were markedly increased
      in mice fed KD for 6 days. Blood beta-hydroxybutyrate levels in the knockout mice
      fed KD for 6 days were comparable to those in wild-type mice fed KD, indicating
      that Fgf21 is not required for ketogenesis. However, the impaired glucose
      tolerance and insulin sensitivity caused by KD feeding were improved in the
      knockout mice. Insulin-stimulated Akt phosphorylation was significantly decreased
      in the white adipose tissue in wild-type mice fed KD compared with those fed
      normal chow, but not in the muscle and liver. Its phosphorylation in the white
      adipose tissue was significantly increased in the knockout mice fed KD compared
      with wild-type mice fed KD. In contrast, hepatic gluconeogenic gene expression in
      Fgf21 knockout mice fed KD was comparable to those in the wild-type mice fed KD.
      CONCLUSIONS/SIGNIFICANCE: The present findings indicate that KD feeding impairs
      insulin sensitivity in mice due to insulin resistance in white adipose tissue. In
      addition, our findings indicate that Fgf21 induced to express by KD is a negative
      regulator of adipocyte insulin sensitivity in adaptation to a low-carbohydrate
      malnutritional state.

PMID- 23874947
TI  - Supercooling as a viable non-freezing cell preservation method of rat
      hepatocytes.
AB  - Supercooling preservation holds the potential to drastically extend the
      preservation time of organs, tissues and engineered tissue products, and fragile
      cell types that do not lend themselves well to cryopreservation or vitrification.
      Here, we investigate the effects of supercooling preservation (SCP at -4(o)C) on
      primary rat hepatocytes stored in cryovials and compare its success (high
      viability and good functional characteristics) to that of static cold storage (CS
      at +4(o)C) and cryopreservation. We consider two prominent preservation solutions
      a) Hypothermosol (HTS-FRS) and b) University of Wisconsin solution (UW) and a
      range of preservation temperatures (-4 to -10 (o)C). We find that there exists an
      optimum temperature (-4(o)C) for SCP of rat hepatocytes which yields the highest
      viability; at this temperature HTS-FRS significantly outperforms UW solution in
      terms of viability and functional characteristics (secretions and enzymatic
      activity in suspension and plate culture). With the HTS-FRS solution we show that
      the cells can be stored for up to a week with high viability (~56%); moreover we
      also show that the preservation can be performed in large batches (50 million
      cells) with equal or better viability and no loss of functionality as compared to
      smaller batches (1.5 million cells) performed in cryovials. 

PMID- 23874948
TI  - Spatio-Temporal Quantification of FRET in living cells by fast time-domain FLIM:
      a comparative study of non-fitting methods [corrected].
AB  - Forster Resonance Energy Transfer (FRET) measured with Fluorescence Lifetime
      Imaging Microscopy (FLIM) is a powerful technique to investigate spatio-temporal
      regulation of protein-protein interactions in living cells. When using standard
      fitting methods to analyze time domain FLIM, the correct estimation of the FRET
      parameters requires a high number of photons and therefore long acquisition times
      which are incompatible with the observation of dynamic protein-protein
      interactions. Recently, non-fitting strategies have been developed for the
      analysis of FLIM images: the polar plot or "phasor" and the minimal fraction of
      interacting donor mfD . We propose here a novel non-fitting strategy based on the
      calculation of moments. We then compare the performance of these three methods
      when shortening the acquisition time: either by reducing the number of counted
      photons N or the number of temporal channels Nch , which is particularly adapted
      for the original fast-FLIM prototype presented in this work that employs the time
      gated approach. Based on theoretical calculations, Monte Carlo simulations and
      experimental data, we determine the domain of validity of each method. We thus
      demonstrate that the polar approach remains accurate for a large range of
      conditions (low N, Nch or small fractions of interacting donor fD ). The validity
      domain of the moments method is more restricted (not applicable when fD <0.25 or
      when Nch  = 4) but it is more precise than the polar approach. We also
      demonstrate that the mfD is robust in all conditions and it is the most precise
      strategy; although it does not strictly provide the fraction of interacting
      donor. We show using the fast-FLIM prototype (with an acquisition rate up to 1
      Hz) that these non-fitting strategies are very powerful for on-line analysis on a
      standard computer and thus for quantifying automatically the spatio-temporal
      activation of Rac-GTPase in living cells by FRET. 

PMID- 23874949
TI  - Clonal dynamics of nasal Staphylococcus aureus and Staphylococcus
      pseudintermedius in dog-owning household members. Detection of MSSA ST(398).
AB  - The objective of this study was to investigate the dynamics of nasal carriage by
      Staphylococcus aureus (SA) and Staphylococcus pseudintermedius (SP) among healthy
      dog-owning household members involved in 7 previous index cases of suspected
      anthropozoonotic (n = 4) and zoonotic (n = 3) interspecies transmission [4 direct
      cases, identical SA (n = 3) or SP (n = 1) in owner and dog; three indirect, SP in
      owner (n = 2) or SA in dog (n = 1)]. Co-carriage with methicillin-resistant
      coagulase-negative staphylococci (MRCoNS) was also evaluated. Sixteen owners and
      10 dogs were sampled once every three months for one year. In total, 50 SA and 31
      SP were analysed by MLST, and SA also by spa typing. All isolates were subjected
      to ApaI/SmaI-PFGE and antimicrobial resistance and virulence profiles were
      determined. All index owners were persistent SA carriers in all direct
      anthropozoonotic transmission cases, while only one dog was persistent SA
      carrier. Owner and dog exhibited a persistent SP carriage status in the direct
      zoonotic transmission case. SP was maintained in the index human over time in one
      indirect-zoonotic transmission case. Only one SP was methicillin-resistant. SA
      belonged to genetic backgrounds of MRSA pandemic clones: CC45, CC121, CC30, CC5
      and CC398. Three individuals carried a MSSA t1451-ST398 clone with the erm(T)
      cadD/cadX resistance genes. SA or SP were persistently detected in the nasal
      cavity of 7 (43.8%) and 2 (12.5%) owners, and in one and 2 dogs, respectively. SA
      was recovered as the single species in 10 owners and in one dog; SP in 3 owners
      and 4 dogs; and both bacterial species in one owner and 4 dogs. Co-carriage of SA
      or SP with MRCoNS isolates was common (30.7%). This is the first study on the
      dynamics of nasal carriage of SA and SP in healthy pet-owning household members.
      Dog-contact may play a role in the staphylococcal species distribution of in
      contact individuals. 

PMID- 23874951
TI  - Gaseous elemental mercury (GEM) emissions from snow surfaces in northern New
      York.
AB  - Snow surface-to-air exchange of gaseous elemental mercury (GEM) was measured
      using a modified Teflon fluorinated ethylene propylene (FEP) dynamic flux chamber
      (DFC) in a remote, open site in Potsdam, New York. Sampling was conducted during
      the winter months of 2011. The inlet and outlet of the DFC were coupled with a
      Tekran Model 2537A mercury (Hg) vapor analyzer using a Tekran Model 1110 two port
      synchronized sampler. The surface GEM flux ranged from -4.47 ng m(-2) hr(-1) to
      9.89 ng m(-2) hr(-1). For most sample periods, daytime GEM flux was strongly
      correlated with solar radiation. The average nighttime GEM flux was slightly
      negative and was not well correlated with any of the measured meteorological
      variables. Preliminary, empirical models were developed to estimate GEM emissions
      from snow surfaces in northern New York. These models suggest that most, if not
      all, of the Hg deposited with and to snow is reemitted to the atmosphere. 

PMID- 23874950
TI  - The dietary protein/carbohydrate ratio differentially modifies lipogenesis and
      protein synthesis in the mammary gland, liver and adipose tissue during gestation
      and lactation.
AB  - During gestation and lactation, a series of metabolic changes that are affected
      by the diet occurs in various organs of the mother. However, little is known
      about how the dietary protein (DP)/carbohydrate (DCH) ratio regulates the
      expression of metabolic genes in the mother. Therefore, the purpose of this work
      was to study the effect of consuming different percentages of DP/DCH,
      specifically 10/73, 20/63 and 30/53%, on the expression of genes involved in
      lipogenesis and protein synthesis in the mammary gland, liver and adipose tissue
      during gestation and lactation in dams. While the amount of weight gained during
      gestation was similar for all groups, only dams fed with 30/53% DP/DCH maintained
      their weight during lactation. In the mammary gland, the expression of the genes
      involved in lipogenesis, specifically SREBP1 and FAS, was dramatically increased,
      and the expression of the genes involved in protein synthesis, such as mTOR1, and
      the phosphorylation of its target protein, S6K, were also increased throughout
      pregnancy and lactation, regardless of the concentration of DP/DCH. In the liver
      and adipose tissue, the expression of the genes and proteins involved in lipid
      metabolism was dependent on the proportion of DP/DCH. The consumption of a low
      protein/high-carbohydrate diet increased the expression of lipogenic genes in the
      liver and adipose tissue and the amount of lipid deposition in the liver.
      Conversely, the consumption of a high-protein/low-carbohydrate diet increased the
      expression of genes involved in amino acid oxidation in the liver during
      gestation. The metabolic adaptations reflected by the changes in the expression
      of metabolic genes indicate that the mammary gland has a priority for milk
      synthesis, whereas the adaptations in the liver and adipose tissue are
      responsible for providing nutrients to the mammary gland to sustain milk
      synthesis. 

PMID- 23874952
TI  - Individual differences in motor timing and its relation to cognitive and fine
      motor skills.
AB  - The present study investigated the relationship between individual differences in
      timing movements at the level of milliseconds and performance on selected
      cognitive and fine motor skills. For this purpose, young adult participants (N =
      100) performed a repetitive movement task paced by an auditory metronome at
      different rates. Psychometric measures included the digit-span and symbol search
      subtasks from the Wechsler battery as well as the Raven SPM. Fine motor skills
      were assessed with the Purdue Pegboard test. Motor timing performance was
      significantly related (mean r = .3) to cognitive measures, and explained both
      unique and shared variance with information-processing speed of Raven's scores.
      No significant relations were found between motor timing measures and fine motor
      skills. These results show that individual differences in cognitive and motor
      timing performance is to some extent dependent upon shared processing not
      associated with individual differences in manual dexterity. 

PMID- 23874953
TI  - Turnover of amyloid precursor protein family members determines their nuclear
      signaling capability.
AB  - The amyloid precursor protein (APP) as well as its homologues, APP-like protein 1
      and 2 (APLP1 and APLP2), are cleaved by alpha-, beta-, and gamma-secretases,
      resulting in the release of their intracellular domains (ICDs). We have shown
      that the APP intracellular domain (AICD) is transported to the nucleus by Fe65
      where they jointly bind the histone acetyltransferase Tip60 and localize to
      spherical nuclear complexes (AFT complexes), which are thought to be sites of
      transcription. We have now analyzed the subcellular localization and turnover of
      the APP family members. Similarly to AICD, the ICD of APLP2 localizes to
      spherical nuclear complexes together with Fe65 and Tip60. In contrast, the ICD of
      APLP1, despite binding to Fe65, does not translocate to the nucleus. In addition,
      APLP1 predominantly localizes to the plasma membrane, whereas APP and APLP2 are
      detected in vesicular structures. APLP1 also demonstrates a much slower turnover
      of the full-length protein compared to APP and APLP2. We further show that the
      ICDs of all APP family members are degraded by the proteasome and that the N
      terminal amino acids of ICDs determine ICD degradation rate. Together, our
      results suggest that different nuclear signaling capabilities of APP family
      members are due to different rates of full-length protein processing and ICD
      proteasomal degradation. Our results provide evidence in support of a common
      nuclear signaling function for APP and APLP2 that is absent in APLP1, but suggest
      that APLP1 has a regulatory role in the nuclear translocation of APP family ICDs
      due to the sequestration of Fe65. 

PMID- 23874954
TI  - Re-docking scheme for generating near-native protein complexes by assembling
      residue interaction fingerprints.
AB  - Interaction profile method is a useful method for processing rigid-body docking.
      After the docking process, the resulting set of docking poses could be classified
      by calculating similarities among them using these interaction profiles to search
      for near-native poses. However, there are some cases where the near-native poses
      are not included in this set of docking poses even when the bound-state
      structures are used. Therefore, we have developed a method for generating near
      native docking poses by introducing a re-docking process. We devised a method for
      calculating the profile of interaction fingerprints by assembling protein
      complexes after determining certain core-protein complexes. For our analysis, we
      used 44 bound-state protein complexes selected from the ZDOCK benchmark dataset
      ver. 2.0, including some protein pairs none of which generated near-native poses
      in the docking process. Consequently, after the re-docking process we obtained
      profiles of interaction fingerprints, some of which yielded near-native poses.
      The re-docking process involved searching for possible docking poses in a
      restricted area using the profile of interaction fingerprints. If the profile
      includes interactions identical to those in the native complex, we obtained near
      native docking poses. Accordingly, near-native poses were obtained for all bound
      state protein complexes examined here. Application of interaction fingerprints to
      the re-docking process yielded structures with more native interactions, even
      when a docking pose, obtained following the initial docking process, contained
      only a small number of native amino acid interactions. Thus, utilization of the
      profile of interaction fingerprints in the re-docking process yielded more near
      native poses. 

PMID- 23874956
TI  - Resampling-based approaches to study variation in morphological modularity.
AB  - Modularity has been suggested to be connected to evolvability because a higher
      degree of independence among parts allows them to evolve as separate units.
      Recently, the Escoufier RV coefficient has been proposed as a measure of the
      degree of integration between modules in multivariate morphometric datasets.
      However, it has been shown, using randomly simulated datasets, that the value of
      the RV coefficient depends on sample size. Also, so far there is no statistical
      test for the difference in the RV coefficient between a priori defined groups of
      observations. Here, we (1), using a rarefaction analysis, show that the value of
      the RV coefficient depends on sample size also in real geometric morphometric
      datasets; (2) propose a permutation procedure to test for the difference in the
      RV coefficient between a priori defined groups of observations; (3) show, through
      simulations, that such a permutation procedure has an appropriate Type I error;
      (4) suggest that a rarefaction procedure could be used to obtain sample-size
      corrected values of the RV coefficient; and (5) propose a nearest-neighbor
      procedure that could be used when studying the variation of modularity in
      geographic space. The approaches outlined here, readily extendable to non
      morphometric datasets, allow study of the variation in the degree of integration
      between a priori defined modules. A Java application--that will allow performance
      of the proposed test using a software with graphical user interface--has also
      been developed and is available at the Morphometrics at Stony Brook Web page
      (http://life.bio.sunysb.edu/morph/).

PMID- 23874955
TI  - sox4 and sox11 function during Xenopus laevis eye development.
AB  - SoxC genes are involved in many developmental processes such as cardiac,
      lymphoid, and bone development. The SoxC gene family is represented by Sox4,
      Sox11, and Sox12. Loss of either Sox4 or Sox11 function is lethal during mouse
      embryogenesis. Here, we demonstrate that sox4 and sox11 are strongly expressed in
      the developing eye, heart as well as brain in Xenopus laevis. Morpholino
      oligonucleotide mediated knock-down approaches in anterior neural tissue revealed
      that interference with either Sox4 or Sox11 function affects eye development. A
      detailed analysis demonstrated strong effects on eye size and retinal lamination.
      Neural induction was unaffected upon Sox4 or Sox11 MO injection and early eye
      field differentiation and cell proliferation were only mildly affected. Depletion
      of both genes, however, led independently to a significant increase in cell
      apoptosis in the eye. In summary, Sox4 and Sox11 are required for Xenopus visual
      system development. 

PMID- 23874957
TI  - Th1-mediated immunity against Helicobacter pylori can compensate for lack of Th17
      cells and can protect mice in the absence of immunization.
AB  - Helicobacter pylori (H. pylori) infection can be significantly reduced by
      immunization in mice. Th17 cells play an essential role in the protective immune
      response. Th1 immunity has also been demonstrated to play a role in the
      protective immune response and can compensate in the absence of IL-17. To further
      address the potential of Th1 immunity, we investigated the efficacy of
      immunization in mice deficient in IL-23p19, a cytokine that promotes Th17 cell
      development. We also examined the course of Helicobacter infection in unimmunized
      mice treated with Th1 promoting cytokine IL-12. C57BL/6, IL-12 p35 KO, and IL-23
      p19 KO mice were immunized and challenged with H. pylori. Protective immunity was
      evaluated by CFU determination and QPCR on gastric biopsies. Gastric and splenic
      IL-17 and IFNgamma levels were determined by PCR or by ELISA. Balb/c mice were
      infected with H. felis and treated with IL-12 therapy and the resulting gastric
      bacterial load and inflammatory response were assessed by histologic evaluation.
      Vaccine induced reductions in bacterial load that were comparable to wild type
      mice were observed in both IL-12 p35 and IL-23 p19 KO mice. In the absence of IL
      23 p19, IL-17 levels remained low but IFNgamma levels increased significantly in
      both immunized challenged and unimmunized/challenged mice. Additionally,
      treatment of H. felis-infected Balb/c mice with IL-12 resulted in increased
      gastric inflammation and the eradication of bacteria in most mice. These data
      suggest that Th1 immunity can compensate for the lack of IL-23 mediated Th17
      responses, and that protective Th1 immunity can be induced in the absence of
      immunization through cytokine therapy of the infected host. 

PMID- 23874958
TI  - S100A8/A9 (calprotectin) negatively regulates G2/M cell cycle progression and
      growth of squamous cell carcinoma.
AB  - Malignant transformation results in abnormal cell cycle regulation and
      uncontrolled growth in head and neck squamous cell carcinoma (HNSCC) and other
      cancers. S100A8/A9 (calprotectin) is a calcium-binding heterodimeric protein
      complex implicated in cell cycle regulation, but the specific mechanism and role
      in cell cycle control and carcinoma growth are not well understood. In HNSCC,
      S100A8/A9 is downregulated at both mRNA and protein levels. We now report that
      downregulation of S100A8/A9 correlates strongly with a loss of cell cycle control
      and increased growth of carcinoma cells. To show its role in carcinogenesis in an
      in vitro model, S100A8/A9 was stably expressed in an S100A8/A9-negative human
      carcinoma cell line (KB cells, HeLa-like). S100A8/A9 expression increases PP2A
      phosphatase activity and p-Chk1 (Ser345) phosphorylation, which appears to signal
      inhibitory phosphorylation of mitotic p-Cdc25C (Ser216) and p-Cdc2 (Thr14/Tyr15)
      to inactivate the G2/M Cdc2/cyclin B1 complex. Cyclin B1 expression then
      downregulates and the cell cycle arrests at the G2/M checkpoint, reducing cell
      division. As expected, S100A8/A9-expressing cells show both decreased anchorage
      dependent and -independent growth and mitotic progression. Using shRNA, silencing
      of S100A8/A9 expression in the TR146 human HNSCC cell line increases growth and
      survival and reduces Cdc2 inhibitory phosphorylation at Thr14/Tyr15. The level of
      S100A8/A9 endogenous expression correlates strongly with the reduced p-Cdc2
      (Thr14/Tyr14) level in HNSCC cell lines, SCC-58, OSCC-3 and UMSCC-17B. S100A8/A9
      mediated control of the G2/M cell cycle checkpoint is, therefore, a likely
      suppressive mechanism in human squamous cell carcinomas and may suggest new
      therapeutic approaches. 

PMID- 23874959
TI  - TCW: transcriptome computational workbench.
AB  - BACKGROUND: The analysis of transcriptome data involves many steps and various
      programs, along with organization of large amounts of data and results. Without a
      methodical approach for storage, analysis and query, the resulting ad hoc
      analysis can lead to human error, loss of data and results, inefficient use of
      time, and lack of verifiability, repeatability, and extensibility. METHODOLOGY:
      The Transcriptome Computational Workbench (TCW) provides Java graphical
      interfaces for methodical analysis for both single and comparative transcriptome
      data without the use of a reference genome (e.g. for non-model organisms). The
      singleTCW interface steps the user through importing transcript sequences (e.g.
      Illumina) or assembling long sequences (e.g. Sanger, 454, transcripts),
      annotating the sequences, and performing differential expression analysis using
      published statistical programs in R. The data, metadata, and results are stored
      in a MySQL database. The multiTCW interface builds a comparison database by
      importing sequence and annotation from one or more single TCW databases, executes
      the ESTscan program to translate the sequences into proteins, and then
      incorporates one or more clusterings, where the clustering options are to execute
      the orthoMCL program, compute transitive closure, or import clusters. Both
      singleTCW and multiTCW allow extensive query and display of the results, where
      singleTCW displays the alignment of annotation hits to transcript sequences, and
      multiTCW displays multiple transcript alignments with MUSCLE or pairwise
      alignments. The query programs can be executed on the desktop for fastest
      analysis, or from the web for sharing the results. CONCLUSION: It is now
      affordable to buy a multi-processor machine, and easy to install Java and MySQL.
      By simply downloading the TCW, the user can interactively analyze, query and view
      their data. The TCW allows in-depth data mining of the results, which can lead to
      a better understanding of the transcriptome. TCW is freely available from
      www.agcol.arizona.edu/software/tcw.

PMID- 23874960
TI  - Capacity and adaptations of general practice during an influenza pandemic.
AB  - BACKGROUND: GPs play a major role in influenza epidemics, and most patients with
      influenza-like-illness (ILI) are treated in general practice or by primary care
      doctors on duty in out-of-hours services (OOH). Little is known about the surge
      capacity in primary care services during an influenza pandemic, and how the
      relationship between them changes. AIM: To investigate how general practice and
      OOH services were used by patients during the 2009 pandemic in Norway and the
      impact of the pandemic on primary care services in comparison to a normal
      influenza season. MATERIALS: Data from electronic remuneration claims from all
      OOH doctors and regular GPs for 2009. METHODS: We conducted a registry-based
      study of all ILI consultations in the 2009 pandemic with the 2008/09 influenza
      season (normal season) as baseline for comparison. RESULTS: The majority (82.2%)
      of ILI consultations during the 2009 pandemic took place in general practice. The
      corresponding number in the 2008/09 season was 89.3%. Compared with general
      practice, the adjusted odds ratio for ILI with all other diagnoses as reference
      in OOH services was 1.23 (95% CI, 1.18, 1.27) for the 2008/2009 season and 1.87
      (95% CI, 1.84, 1.91) for the pandemic influenza season. In total there was a 3.3
      fold increase in ILI consultations during the pandemic compared to the 2008/09
      season. A 5.5-fold increase of ILI consultations were observed in OOH services in
      comparison to the 2008/09 season. Children and young adults with ILI were the
      most frequent users of OOH services during influenza periods. CONCLUSIONS: The
      autumn pandemic wave resulted in a significantly increased demand on primary care
      services. However, GPs in primary care services in Norway showed the ability to
      increase capacity in a situation with increased patient demand.

PMID- 23874961
TI  - Characterization of the interaction between the cohesin subunits Rad21 and SA1/2.
AB  - The cohesin complex is responsible for the fidelity of chromosomal segregation
      during mitosis. It consists of four core subunits, namely Rad21/Mcd1/Scc1, Smc1,
      Smc3, and one of the yeast Scc3 orthologs SA1 or SA2. Sister chromatid cohesion
      is generated during DNA replication and maintained until the onset of anaphase.
      Among the many proposed models of the cohesin complex, the 'core' cohesin
      subunits Smc1, Smc3, and Rad21 are almost universally displayed as tripartite
      ring. However, other than its supportive role in the cohesin ring, little is
      known about the fourth core subunit SA1/SA2. To gain deeper insight into the
      function of SA1/SA2 in the cohesin complex, we have mapped the interactive
      regions of SA2 and Rad21 in vitro and ex vivo. Whereas SA2 interacts with Rad21
      through a broad region (301-750 aa), Rad21 binds to SA proteins through two SA
      binding motifs on Rad21, namely N-terminal (NT) and middle part (MP) SA-binding
      motif, located at 60-81 aa of the N-terminus and 383-392 aa of the MP of Rad21,
      respectively. The MP SA-binding motif is a 10 amino acid, alpha-helical motif.
      Deletion of these 10 amino acids or mutation of three conserved amino acids
      (L(385), F(389), and T(390)) in this alpha-helical motif significantly hinders
      Rad21 from physically interacting with SA1/2. Besides the MP SA-binding motif,
      the NT SA-binding motif is also important for SA1/2 interaction. Although
      mutations on both SA-binding motifs disrupt Rad21-SA1/2 interaction, they had no
      apparent effect on the Smc1-Smc3-Rad21 interaction. However, the Rad21-Rad21
      dimerization was reduced by the mutations, indicating potential involvement of
      the two SA-binding motifs in the formation of the two-ring handcuff for
      chromosomal cohesion. Furthermore, mutant Rad21 proteins failed to significantly
      rescue precocious chromosome separation caused by depletion of endogenous Rad21
      in mitotic cells, further indicating the physiological significance of the two SA
      binding motifs of Rad21. 

PMID- 23874962
TI  - Molecular characteristics and efficacy of 16D10 siRNAs in inhibiting root-knot
      nematode infection in transgenic grape hairy roots.
AB  - Root-knot nematodes (RKNs) infect many annual and perennial crops and are the
      most devastating soil-born pests in vineyards. To develop a biotech-based
      solution for controlling RKNs in grapes, we evaluated the efficacy of plant
      derived RNA interference (RNAi) silencing of a conserved RKN effector gene,
      16D10, for nematode resistance in transgenic grape hairy roots. Two hairpin-based
      silencing constructs, containing a stem sequence of 42 bp (pART27-42) or 271 bp
      (pART27-271) of the 16D10 gene, were transformed into grape hairy roots and
      compared for their small interfering RNA (siRNA) production and efficacy on
      suppression of nematode infection. Transgenic hairy root lines carrying either of
      the two RNAi constructs showed less susceptibility to nematode infection compared
      with control. Small RNA libraries from four pART27-42 and two pART27-271 hairy
      root lines were sequenced using an Illumina sequencing technology. The pART27-42
      lines produced hundred times more 16D10-specific siRNAs than the pART27-271
      lines. On average the 16D10 siRNA population had higher GC content than the 16D10
      stem sequences in the RNAi constructs, supporting previous observation that plant
      dicer-like enzymes prefer GC-rich sequences as substrates for siRNA production.
      The stems of the 16D10 RNAi constructs were not equally processed into siRNAs.
      Several hot spots for siRNA production were found in similar positions of the
      hairpin stems in pART27-42 and pART27-271. Interestingly, stem sequences at the
      loop terminus produced more siRNAs than those at the stem base. Furthermore, the
      relative abundance of guide and passenger single-stranded RNAs from putative
      siRNA duplexes was largely correlated with their 5' end thermodynamic strength.
      This study demonstrated the feasibility of using a plant-derived RNAi approach
      for generation of novel nematode resistance in grapes and revealed several
      interesting molecular characteristics of transgene siRNAs important for
      optimizing plant RNAi constructs. 

PMID- 23874963
TI  - A single amino acid substitution in the core protein of West Nile virus increases
      resistance to acidotropic compounds.
AB  - West Nile virus (WNV) is a worldwide distributed mosquito-borne flavivirus that
      naturally cycles between birds and mosquitoes, although it can infect multiple
      vertebrate hosts including horses and humans. This virus is responsible for
      recurrent epidemics of febrile illness and encephalitis, and has recently become
      a global concern. WNV requires to transit through intracellular acidic
      compartments at two different steps to complete its infectious cycle. These
      include fusion between the viral envelope and the membrane of endosomes during
      viral entry, and virus maturation in the trans-Golgi network. In this study, we
      followed a genetic approach to study the connections between viral components and
      acidic pH. A WNV mutant with increased resistance to the acidotropic compound
      NH4Cl, which blocks organelle acidification and inhibits WNV infection, was
      selected. Nucleotide sequencing revealed that this mutant displayed a single
      amino acid substitution (Lys 3 to Glu) on the highly basic internal capsid or
      core (C) protein. The functional role of this replacement was confirmed by its
      introduction into a WNV infectious clone. This single amino acid substitution
      also increased resistance to other acidification inhibitor (concanamycin A) and
      induced a reduction of the neurovirulence in mice. Interestingly, a naturally
      occurring accompanying mutation found on prM protein abolished the resistant
      phenotype, supporting the idea of a genetic crosstalk between the internal C
      protein and the external glycoproteins of the virion. The findings here reported
      unveil a non-previously assessed connection between the C viral protein and the
      acidic pH necessary for entry and proper exit of flaviviruses. 

PMID- 23874965
TI  - Distal and proximal actions of peptide pheromone M-factor control different
      conjugation steps in fission yeast.
AB  - Mating pheromone signaling is essential for conjugation between haploid cells of
      P-type (P-cells) and haploid cells of M-type (M-cells) in Schizosaccharomyces
      pombe. A peptide pheromone, M-factor, produced by M-cells is recognized by the
      receptor of P-cells. An M-factor-less mutant, in which the M-factor-encoding
      genes are deleted, is completely sterile. In liquid culture, sexual agglutination
      was not observed in the mutant, but it could be recovered by adding exogenous
      synthetic M-factor, which stimulated expression of the P-type-specific cell
      adhesion protein, Map4. Exogenous M-factor, however, failed to recover the cell
      fusion defect in the M-factor-less mutant. When M-factor-less cells were added to
      a mixture of wild-type P- and M-cells, marked cell aggregates were formed.
      Notably, M-factor-less mutant cells were also incorporated in these aggregates.
      In this mixed culture, P-cells conjugated preferentially with M-cells secreting M
      factor, and rarely with M-factor-less M-cells. The kinetics of mating parameters
      in liquid culture revealed that polarized growth commenced from the contact
      region of opposite mating-type cells. Taken together, these findings indicate
      that M-factor at a low concentration induces adhesin expression, leading to
      initial cell-cell adhesion in a type of "distal pheromone action", but M-factor
      that is secreted directly in the proximity of the adhered P-cells may be
      necessary for cell fusion in a type of "proximal pheromone action". 

PMID- 23874964
TI  - The synthetic amphipathic peptidomimetic LTX109 is a potent fungicide that
      disturbs plasma membrane integrity in a sphingolipid dependent manner.
AB  - The peptidomimetic LTX109 (arginine-tertbutyl tryptophan-arginine-phenylethan)
      was previously shown to have antibacterial properties. Here, we investigated the
      activity of this novel antimicrobial peptidomimetic on the yeast Saccharomyces
      cerevisiae. We found that LTX109 was an efficient fungicide that killed all
      viable cells in an exponentially growing population as well as a large proportion
      of cells in biofilm formed on an abiotic surface. LTX109 had similar killing
      kinetics to the membrane-permeabilizing fungicide amphotericin B, which led us to
      investigate the ability of LTX109 to disrupt plasma membrane integrity. S.
      cerevisiae cells exposed to a high concentration of LTX109 showed rapid release
      of potassium and amino acids, suggesting that LTX109 acted by destabilizing the
      plasma membrane. This was supported by the finding that cells were permeable to
      the fluorescent nucleic acid stain SYTOX Green after a few minutes of LTX109
      treatment. We screened a haploid S. cerevisiae gene deletion library for mutants
      resistant to LTX109 to uncover potential molecular targets. Eight genes conferred
      LTX109 resistance when deleted and six were involved in the sphingolipid
      biosynthetic pathway (SUR1, SUR2, SKN1, IPT1, FEN1 and ORM2). The involvement of
      all of these genes in the biosynthetic pathway for the fungal-specific lipids
      mannosylinositol phosphorylceramide (MIPC) and mannosyl di-(inositol phosphoryl)
      ceramide (M(IP)2C) suggested that these lipids were essential for LTX109
      sensitivity. Our observations are consistent with a model in which LTX109 kills
      S. cerevisiae by nonspecific destabilization of the plasma membrane through
      direct or indirect interaction with the sphingolipids. 

PMID- 23874966
TI  - Efficient induction of Wheat-agropyron cristatum 6P translocation lines and GISH
      detection.
AB  - The narrow genetic background restricts wheat yield and quality improvement. The
      wild relatives of wheat are the huge gene pools for wheat improvement and can
      broaden its genetic basis. Production of wheat-alien translocation lines can
      transfer alien genes to wheat. So it is important to develop an efficient method
      to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome)
      carries many potential genes beneficial to disease resistance, stress tolerance
      and high yield. Chromosome 6P possesses the desirable genes exhibiting good
      agronomic traits, such as high grain number per spike, powdery mildew resistance
      and stress tolerance. In this study, the wheat-A. cristatum disomic addition was
      used as bridge material to produce wheat-A. cristatum translocation lines induced
      by (60)Co-gammairradiation. The results of genomic in situ hybridization showed
      that 216 plants contained alien chromosome translocation among 571 self
      pollinated progenies. The frequency of translocation was 37.83%, much higher than
      previous reports. Moreover, various alien translocation types were identified.
      The analysis of M2 showed that 62.5% of intergeneric translocation lines grew
      normally without losing the translocated chromosomes. The paper reported a high
      efficient technical method for inducing alien translocation between wheat and
      Agropyroncristatum. Additionally, these translocation lines will be valuable for
      not only basic research on genetic balance, interaction and expression of
      different chromosome segments of wheat and alien species, but also wheat breeding
      programs to utilize superior agronomic traits and good compensation effect from
      alien chromosomes. 

PMID- 23874967
TI  - A mitogenomic phylogeny of living primates.
AB  - Primates, the mammalian order including our own species, comprise 480 species in
      78 genera. Thus, they represent the third largest of the 18 orders of eutherian
      mammals. Although recent phylogenetic studies on primates are increasingly built
      on molecular datasets, most of these studies have focused on taxonomic subgroups
      within the order. Complete mitochondrial (mt) genomes have proven to be extremely
      useful in deciphering within-order relationships even up to deep nodes. Using 454
      sequencing, we sequenced 32 new complete mt genomes adding 20 previously not
      represented genera to the phylogenetic reconstruction of the primate tree. With
      13 new sequences, the number of complete mt genomes within the parvorder
      Platyrrhini was widely extended, resulting in a largely resolved branching
      pattern among New World monkey families. We added 10 new Strepsirrhini mt genomes
      to the 15 previously available ones, thus almost doubling the number of mt
      genomes within this clade. Our data allow precise date estimates of all nodes and
      offer new insights into primate evolution. One major result is a relatively young
      date for the most recent common ancestor of all living primates which was
      estimated to 66-69 million years ago, suggesting that the divergence of extant
      primates started close to the K/T-boundary. Although some relationships remain
      unclear, the large number of mt genomes used allowed us to reconstruct a robust
      primate phylogeny which is largely in agreement with previous publications.
      Finally, we show that mt genomes are a useful tool for resolving primate
      phylogenetic relationships on various taxonomic levels. 

PMID- 23874968
TI  - Inhibition of inducible heat shock protein-70 (hsp72) enhances bortezomib-induced
      cell death in human bladder cancer cells.
AB  - The proteasome inhibitor bortezomib (Velcade) is a promising new agent for
      bladder cancer therapy, but inducible cytoprotective mechanisms may limit its
      potential efficacy. We used whole genome mRNA expression profiling to study the
      effects of bortezomib on stress-induced gene expression in a panel of human
      bladder cancer cell lines. Bortezomib induced strong upregulation of the
      inducible HSP70 isoforms HSPA1A and HSPA1B isoforms of Hsp72 in 253J B-V and
      SW780 (HSPA1A(high)) cells, but only induced the HSPA1B isoform in UM-UC10 and UM
      UC13 (HSPA1A(low)) cells. Bortezomib stimulated the binding of heat shock factor
      1 (HSF1) to the HSPA1A promoter in 253JB-V but not in UM-UC13 cells. Methylation
      specific PCR revealed that the HSPA1A promoter was methylated in the HSPA1A(low)
      cell lines (UM-UC10 and UM-UC13), and exposure to the chromatin demethylating
      agent 5-aza-2'-deoxycytidine restored HSPA1A expression. Overexpression of Hsp72
      promoted bortezomib resistance in the UM-UC10 and UM-UC13 cells, whereas
      transient knockdown of HSPA1B further sensitized these cells to bortezomib, and
      exposure to the chemical HSF1 inhibitor KNK-437 promoted bortezomib sensitivity
      in the 253J B-V cells. Finally, shRNA-mediated stable knockdown of Hsp72 in 253J
      B-V promoted sensitivity to bortezomib in vitro and in tumor xenografts in vivo.
      Together, our results provide proof-of-concept for using Hsp72 inhibitors to
      promote bortezomib sensitivity in bladder cancers and suggest that selective
      targeting of HSPA1B could produce synthetic lethality in tumors that display
      HSPA1A promoter methylation. 

PMID- 23874969
TI  - Endothelial cells potentiate interferon-gamma production in a novel tripartite
      culture model of human cerebral malaria.
AB  - We have established a novel in vitro co-culture system of human brain endothelial
      cells (HBEC), Plasmodium falciparum parasitised red blood cells (iRBC) and
      peripheral blood mononuclear cells (PBMC), in order to simulate the chief
      pathophysiological lesion in cerebral malaria (CM). This approach has revealed a
      previously unsuspected pro-inflammatory role of the endothelial cell through
      potentiating the production of interferon (IFN)-gamma by PBMC and concurrent
      reduction of interleukin (IL)-10. The IFN-gamma increased the expression of
      CXCL10 and intercellular adhesion molecule (ICAM)-1, both of which have been
      shown to be crucial in the pathogenesis of CM. There was a shift in the ratio of
      IL-10:IFN-gamma protein from >1 to <1 in the presence of HBEC, associated with
      the pro-inflammatory process in this model. For this to occur, a direct contact
      between PBMC and HBEC, but not PBMC and iRBC, was necessary. These results
      support HBEC playing an active role in the pathogenesis of CM. Thus, if these
      findings reflect the pathogenesis of CM, inhibition of HBEC and PBMC interactions
      might reduce the occurrence, or improve the prognosis, of the condition. 

PMID- 23874970
TI  - LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression
      pattern reveals non-vascular sites of COX-2 expression.
AB  - There are two schools of thought regarding the cyclooxygenase (COX) isoform
      active in the vasculature. Using urinary prostacyclin markers some groups have
      proposed that vascular COX-2 drives prostacyclin release. In contrast, we and
      others have found that COX-1, not COX-2, is responsible for vascular prostacyclin
      production. Our experiments have relied on immunoassays to detect the
      prostacyclin breakdown product, 6-keto-PGF1alpha and antibodies to detect COX-2
      protein. Whilst these are standard approaches, used by many laboratories,
      antibody-based techniques are inherently indirect and have been criticized as
      limiting the conclusions that can be drawn. To address this question, we measured
      production of prostanoids, including 6-keto-PGF1alpha, by isolated vessels and in
      the circulation in vivo using liquid chromatography tandem mass spectrometry and
      found values essentially identical to those obtained by immunoassay. In addition,
      we determined expression from the Cox2 gene using a knockin reporter mouse in
      which luciferase activity reflects Cox2 gene expression. Using this we confirm
      the aorta to be essentially devoid of Cox2 driven expression. In contrast,
      thymus, renal medulla, and regions of the brain and gut expressed substantial
      levels of luciferase activity, which correlated well with COX-2-dependent
      prostanoid production. These data are consistent with the conclusion that COX-1
      drives vascular prostacyclin release and puts the sparse expression of Cox2 in
      the vasculature in the context of the rest of the body. In doing so, we have
      identified the thymus, gut, brain and other tissues as target organs for
      consideration in developing a new understanding of how COX-2 protects the
      cardiovascular system. 

PMID- 23874971
TI  - Structure-guided design of an engineered streptavidin with reusability to purify
      streptavidin-binding peptide tagged proteins or biotinylated proteins.
AB  - Development of a high-affinity streptavidin-binding peptide (SBP) tag allows the
      tagged recombinant proteins to be affinity purified using the streptavidin matrix
      without the need of biotinylation. The major limitation of this powerful
      technology is the requirement to use biotin to elute the SBP-tagged proteins from
      the streptavidin matrix. Tight biotin binding by streptavidin essentially allows
      the matrix to be used only once. To address this problem, differences in
      interactions of biotin and SBP with streptavidin were explored. Loop3-4 which
      serves as a mobile lid for the biotin binding pocket in streptavidin is in the
      closed state with biotin binding. In contrast, this loop is in the open state
      with SBP binding. Replacement of glycine-48 with a bulkier residue (threonine) in
      this loop selectively reduces the biotin binding affinity (Kd) from 4 * 10(-14) M
      to 4.45 * 10(-10) M without affecting the SBP binding affinity. Introduction of a
      second mutation (S27A) to the first mutein (G48T) results in the development of a
      novel engineered streptavidin SAVSBPM18 which could be recombinantly produced in
      the functional form from Bacillus subtilis via secretion. To form an intact
      binding pocket for tight binding of SBP, two diagonally oriented subunits in a
      tetrameric streptavidin are required. It is vital for SAVSBPM18 to be stably in
      the tetrameric state in solution. This was confirmed using an HPLC/Laser light
      scattering system. SAVSBPM18 retains high binding affinity to SBP but has
      reversible biotin binding capability. The SAVSBPM18 matrix can be applied to
      affinity purify SBP-tagged proteins or biotinylated molecules to homogeneity with
      high recovery in a reusable manner. A mild washing step is sufficient to
      regenerate the matrix which can be reused for multiple rounds. Other applications
      including development of automated protein purification systems, lab-on-a-chip
      micro-devices, reusable biosensors, bioreactors and microarrays, and strippable
      detection agents for various blots are possible.

PMID- 23874972
TI  - Immune-related transcriptome of Coptotermes formosanus Shiraki workers: the
      defense mechanism.
AB  - Formosan subterranean termites, Coptotermes formosanus Shiraki, live socially in
      microbial-rich habitats. To understand the molecular mechanism by which termites
      combat pathogenic microbes, a full-length normalized cDNA library and four
      Suppression Subtractive Hybridization (SSH) libraries were constructed from
      termite workers infected with entomopathogenic fungi (Metarhizium anisopliae and
      Beauveria bassiana), Gram-positive Bacillus thuringiensis and Gram-negative
      Escherichia coli, and the libraries were analyzed. From the high quality
      normalized cDNA library, 439 immune-related sequences were identified. These
      sequences were categorized as pattern recognition receptors (47 sequences),
      signal modulators (52 sequences), signal transducers (137 sequences), effectors
      (39 sequences) and others (164 sequences). From the SSH libraries, 27, 17, 22 and
      15 immune-related genes were identified from each SSH library treated with M.
      anisopliae, B. bassiana, B. thuringiensis and E. coli, respectively. When the
      normalized cDNA library was compared with the SSH libraries, 37 immune-related
      clusters were found in common; 56 clusters were identified in the SSH libraries,
      and 259 were identified in the normalized cDNA library. The immune-related gene
      expression pattern was further investigated using quantitative real time PCR
      (qPCR). Important immune-related genes were characterized, and their potential
      functions were discussed based on the integrated analysis of the results. We
      suggest that normalized cDNA and SSH libraries enable us to discover functional
      genes transcriptome. The results remarkably expand our knowledge about immune
      inducible genes in C. formosanus Shiraki and enable the future development of
      novel control strategies for the management of Formosan subterranean termites. 

PMID- 23874973
TI  - Emerging role of calcium-activated potassium channel in the regulation of cell
      viability following potassium ions challenge in HEK293 cells and pharmacological
      modulation.
AB  - Emerging evidences suggest that Ca(2+)activated-K(+)-(BK) channel is involved in
      the regulation of cell viability. The changes of the cell viability observed
      under hyperkalemia (15 mEq/L) or hypokalemia (0.55 mEq/L) conditions were
      investigated in HEK293 cells expressing the hslo subunit (hslo-HEK293) in the
      presence or absence of BK channel modulators. The BK channel openers(10(-11)-10(
      3)M) were: acetazolamide(ACTZ), Dichlorphenamide(DCP), methazolamide(MTZ),
      bendroflumethiazide(BFT), ethoxzolamide(ETX), hydrochlorthiazide(HCT),
      quercetin(QUERC), resveratrol(RESV) and NS1619; and the BK channel blockers(2 x
      10(-7)M-5 x 10(-3)M) were: tetraethylammonium(TEA), iberiotoxin(IbTx) and
      charybdotoxin(ChTX). Experiments on cell viability and channel currents were
      performed using cell counting kit-8 and patch-clamp techniques, respectively.
      Hslo whole-cell current was potentiated by BK channel openers with different
      potency and efficacy in hslo-HEK293. The efficacy ranking of the openers at -60
      mV(Vm) was BFT> ACTZ >DCP >=RESV>= ETX> NS1619> MTZ>= QUERC; HCT was not
      effective. Cell viability after 24 h of incubation under hyperkalemia was
      enhanced by 82+6% and 33+7% in hslo-HEK293 cells and HEK293 cells, respectively.
      IbTx, ChTX and TEA enhanced cell viability in hslo-HEK293. BK openers prevented
      the enhancement of the cell viability induced by hyperkalemia or IbTx in hslo
      HEK293 showing an efficacy which was comparable with that observed as BK openers.
      BK channel modulators failed to affect cell currents and viability under
      hyperkalemia conditions in the absence of hslo subunit. In contrast, under
      hypokalemia cell viability was reduced by -22+4% and -23+6% in hslo-HEK293 and
      HEK293 cells, respectively; the BK channel modulators failed to affect this
      parameter in these cells. In conclusion, BK channel regulates cell viability
      under hyperkalemia but not hypokalemia conditions. BFT and ACTZ were the most
      potent drugs either in activating the BK current and in preventing the cell
      proliferation induced by hyperkalemia. These findings may have relevance in
      disorders associated with abnormal K(+) ion homeostasis including periodic
      paralysis and myotonia.

PMID- 23874974
TI  - Over expression of minichromosome maintenance genes is clinically correlated to
      cervical carcinogenesis.
AB  - Minichromosome Maintenance (MCM) proteins play important roles in cell cycle
      progression by mediating DNA replication initiation and elongation. Among 10 MCM
      homologues MCM 2-7 form a hexamer and assemble to the pre-replication complex
      acting as replication licensing factors. Binding and function of MCM2-7 to pre
      replication complex is regulated by MCM10 mediated binding of RECQL4 with MCM2-7.
      The purpose of this study is to explore the role of MCMs in cervical cancer and
      their correlation with the clinical parameters of cervical cancer. We have
      investigated sixty primary cervical cancer tissue samples, eight cervical cancer
      cell lines and thirty hysterectomised normal cervical tissue. The expression
      profiling of MCMs was done using semi-quantitative RT-PCR, immunoblotting and
      immunohistochemistry. MCM2, 4, 5, 6, 7, 10 and RECQL4 are significantly over
      expressed in cervical cancer. Among these, MCM4, 6 and 10 show increased
      frequency of over expression along with advancement of tumor stages. MCM4, 5 and
      6 also show differential expression in different types of lesion, while MCM2 and
      MCM10 are over expressed in cervical cancer irrespective of clinico-pathological
      parameters. Our data indicates the role of MCM4, MCM5, MCM6, MCM10 and RECQL4 in
      the progression of cervical cancer. 

PMID- 23874976
TI  - Long-term temporal analysis of the human fecal microbiota revealed a stable core
      of dominant bacterial species.
AB  - Next-generation sequencing has greatly contributed to an improved ecological
      understanding of the human gut microbiota. Nevertheless, questions remain
      regarding the characteristics of this ecosystem and the ecological processes that
      shape it, and controversy has arisen regarding the stability of the bacterial
      populations and the existence of a temporal core. In this study, we have
      characterized the fecal microbial communities of three human individuals over a
      one-year period by 454 pyrosequencing of 16S rRNA tags in order to investigate
      the temporal characteristics of the bacterial communities. The findings revealed
      a temporal core of 33 to 40 species-level Operational Taxonomic Units (OTUs)
      within subjects. Although these OTUs accounted only for around 12% of the total
      OTUs detected, they added up to >75% of the total sequences obtained for each
      individual. In order to determine the capacity of the sequencing and
      bioinformatic approaches applied during this study to accurately determine the
      proportion of a core microbiota, we analyzed the fecal microbiota of nine mice
      with a defined three-member community. This experiment revealed that the
      sequencing approach inflated the amount of rare OTUs, which introduced a
      significant degree of artificial variation across samples, and hence reduced the
      apparent fraction of shared OTUs. However, when assessing the data quantitatively
      by focusing on dominant lineages, the sequencing approaches deliver an accurate
      representation of the community. In conclusion, this study revealed that the
      human fecal microbiota is dominated by around 40 species that maintain persistent
      populations over the duration of one year. The findings allow conclusions about
      the ecological factors that shape the community and support the concept of a
      homeostatic ecosystem controlled largely by deterministic processes. Our analysis
      of a three-member community revealed that methodological artifacts of OTU-based
      approaches complicate core calculations, and these limitations have to be
      considered in the interpretation of microbiome studies. 

PMID- 23874975
TI  - A lover and a fighter: the genome sequence of an entomopathogenic nematode
      Heterorhabditis bacteriophora.
AB  - Heterorhabditis bacteriophora are entomopathogenic nematodes that have evolved a
      mutualism with Photorhabdus luminescens bacteria to function as highly virulent
      insect pathogens. The nematode provides a safe harbor for intestinal symbionts in
      soil and delivers the symbiotic bacteria into the insect blood. The symbiont
      provides virulence and toxins, metabolites essential for nematode reproduction,
      and antibiotic preservation of the insect cadaver. Approximately half of the
      21,250 putative protein coding genes identified in the 77 Mbp high quality draft
      H. bacteriophora genome sequence were novel proteins of unknown function lacking
      homologs in Caenorhabditis elegans or any other sequenced organisms. Similarly,
      317 of the 603 predicted secreted proteins are novel with unknown function in
      addition to 19 putative peptidases, 9 peptidase inhibitors and 7 C-type lectins
      that may function in interactions with insect hosts or bacterial symbionts. The
      134 proteins contained mariner transposase domains, of which there are none in C.
      elegans, suggesting an invasion and expansion of mariner transposons in H.
      bacteriophora. Fewer Kyoto Encyclopedia of Genes and Genomes Orthologies in
      almost all metabolic categories were detected in the genome compared with 9 other
      sequenced nematode genomes, which may reflect dependence on the symbiont or
      insect host for these functions. The H. bacteriophora genome sequence will
      greatly facilitate genetics, genomics and evolutionary studies to gain
      fundamental knowledge of nematode parasitism and mutualism. It also elevates the
      utility of H. bacteriophora as a bridge species between vertebrate parasitic
      nematodes and the C. elegans model. 

PMID- 23874977
TI  - The human TUT1 nucleotidyl transferase as a global regulator of microRNA
      abundance.
AB  - Post-transcriptional modifications of miRNAs with 3' non-templated nucleotide
      additions (NTA) are a common phenomenon, and for a handful of miRNAs the
      additions have been demonstrated to modulate miRNA stability. However, it is
      unknown for the vast majority of miRNAs whether nucleotide additions are
      associated with changes in miRNA expression levels. We previously showed that
      miRNA 3' additions are regulated by multiple nucleotidyl transferase enzymes.
      Here we examine the changes in abundance of miRNAs that exhibit altered 3' NTA
      following the suppression of a panel of nucleotidyl transferases in cancer cell
      lines. Among the miRNAs examined, those with increased 3' additions showed a
      significant decrease in abundance. More specifically, miRNAs that gained a 3'
      uridine were associated with the greatest decrease in expression, consistent with
      a model in which 3' uridylation influences miRNA stability. We also observed that
      suppression of one nucleotidyl transferase, TUT1, resulted in a global decrease
      in miRNA levels of approximately 40% as measured by qRT-PCR-based miRNA
      profiling. The mechanism of this global miRNA suppression appears to be indirect,
      as it occurred irrespective of changes in 3' nucleotide addition. Also,
      expression of miRNA primary transcripts did not decrease following TUT1
      knockdown, indicating that the mechanism is post-transcriptional. In conclusion,
      our results suggest that TUT1 affects miRNAs through both a direct effect on 3'
      nucleotide additions to specific miRNAs and a separate, indirect effect on miRNA
      abundance more globally. 

PMID- 23874978
TI  - Methylprednisolone stiffens aortas in lipopolysaccharide-induced chronic
      inflammation in rats.
AB  - INTRODUCTION: Glucocorticoids are commonly used as therapeutic agents in many
      acute and chronic inflammatory and auto-immune diseases. The current study
      investigated the effects of methylprednisolone (a synthetic glucocorticoid) on
      aortic distensibility and vascular resistance in lipopolysaccharide-induced
      chronic inflammation in male Wistar rats. METHODS: Chronic inflammation was
      induced by implanting a subcutaneous slow-release ALZET osmotic pump (1 mg kg(-1)
      day(-1) lipopolysaccharide) for either 2 or 4 weeks. Arterial wave transit time
      (tau) was derived to describe the elastic properties of aortas using the impulse
      response function of the filtered aortic input impedance spectra. RESULTS: Long
      term lipopolysaccharide challenge enhanced the expression of advanced glycation
      end products (AGEs) in the aortas. Lipopolysaccharide also upregulated the
      inducible form of nitric oxide synthase to produce high levels of nitric oxide
      (NO), which resulted in vasodilation, as evidenced by the fall in total
      peripheral resistance (Rp ). However, lipopolysaccharide challenge did not
      influence the elastic properties of aortas, as shown by the unaltered tau. The NO
      mediated vascular relaxation may counterbalance the AGEs-induced arterial
      stiffening so that the aortic distensibility remained unaltered. Treating
      lipopolysaccharide-challenged rats with methylprednisolone prevented peripheral
      vasodilation because of its ability to increase Rp . However, methylprednisolone
      produced an increase in aorta stiffness, as manifested by the significant decline
      in tau. The diminished aortic distensibility by methylprednisolone paralleled a
      significant reduction in NO plasma levels, in the absence of any significant
      changes in AGEs content. CONCLUSION: Methylprednisolone stiffens aortas and
      elastic arteries in lipopolysaccharide-induced chronic inflammation in rats, for
      NO activity may be dominant as a counteraction of AGEs.

PMID- 23874979
TI  - ERK positive feedback regulates a widespread network of tyrosine phosphorylation
      sites across canonical T cell signaling and actin cytoskeletal proteins in Jurkat
      T cells.
AB  - Competing positive and negative signaling feedback pathways play a critical role
      in tuning the sensitivity of T cell receptor activation by creating an
      ultrasensitive, bistable switch to selectively enhance responses to foreign
      ligands while suppressing signals from self peptides. In response to T cell
      receptor agonist engagement, ERK is activated to positively regulate T cell
      receptor signaling through phosphorylation of Ser(59) Lck. To obtain a wide-scale
      view of the role of ERK in propagating T cell receptor signaling, a quantitative
      phosphoproteomic analysis of 322 tyrosine phosphorylation sites by mass
      spectrometry was performed on the human Jurkat T cell line in the presence of
      U0126, an inhibitor of ERK activation. Relative to controls, U0126-treated cells
      showed constitutive decreases in phosphorylation through a T cell receptor
      stimulation time course on tyrosine residues found on upstream signaling proteins
      (CD3 chains, Lck, ZAP-70), as well as downstream signaling proteins (VAV1,
      PLCgamma1, Itk, NCK1). Additional constitutive decreases in phosphorylation were
      found on the majority of identified proteins implicated in the regulation of
      actin cytoskeleton pathway. Although the majority of identified sites on T cell
      receptor signaling proteins showed decreases in phosphorylation, Tyr(598) of ZAP
      70 showed elevated phosphorylation in response to U0126 treatment, suggesting
      differential regulation of this site via ERK feedback. These findings shed new
      light on ERK's role in positive feedback in T cell receptor signaling and reveal
      novel signaling events that are regulated by this kinase, which may fine tune T
      cell receptor activation. 

PMID- 23874980
TI  - Ecological and genetic differences between Cacopsylla melanoneura (Hemiptera,
      Psyllidae) populations reveal species host plant preference.
AB  - The psyllid Cacopsylla melanoneura is considered one of the vectors of
      'Candidatus Phytoplasma mali', the causal agent of apple proliferation disease.
      In Northern Italy, overwintered C. melanoneura adults reach apple and hawthorn
      around the end of January. Nymph development takes place between March and the
      end of April. The new generation adults migrate onto conifers around mid-June and
      come back to the host plant species after overwintering. In this study we
      investigated behavioural differences, genetic differentiation and gene flow
      between samples of C. melanoneura collected from the two different host plants.
      Further analyses were performed on some samples collected from conifers. To
      assess the ecological differences, host-switching experiments were conducted on
      C. melanoneura samples collected from apple and hawthorn. Furthermore, the
      genetic structure of the samples was studied by genotyping microsatellite
      markers. The examined C. melanoneura samples performed better on their native
      host plant species. This was verified in terms of oviposition and development of
      the offspring. Data resulting from microsatellite analysis indicated a low, but
      statistically significant difference between collected-from-apple and hawthorn
      samples. In conclusion, both ecological and genetic results indicate a
      differentiation between C. melanoneura samples associated with the two host
      plants. 

PMID- 23874981
TI  - Increased dendritic spine density and tau expression are associated with
      individual differences in steroidal regulation of male sexual behavior.
AB  - Male sexual behavior (MSB) is modulated by gonadal steroids, yet this
      relationship is highly variable across species and between individuals. A
      significant percentage (~30%) of B6D2F1 hybrid male mice demonstrate MSB after
      long-term orchidectomy (herein after referred to as "maters"), providing an
      opportunity to examine the mechanisms that underlie individual differences in
      steroidal regulation of MSB. Use of gene expression arrays comparing maters and
      non-maters has provided a first pass look at the genetic underpinnings of steroid
      independent MSB. Surprisingly, of the ~500 genes in the medial preoptic area
      (MPOA) that differed between maters and non-maters, no steroid hormone or
      receptor genes were differentially expressed between the two groups.
      Interestingly, best known for their association with Alzheimer's disease, amyloid
      precursor protein (APP) and the microtubule-associated protein tau (MAPT) were
      elevated in maters. Increased levels of their protein products (APP and tau) in
      their non-pathological states have been implicated in cell survival,
      neuroprotection, and supporting synaptic integrity. Here we tested transgenic
      mice that overexpress tau and found facilitated mounting and intromission
      behavior after long-term orchidectomy relative to littermate controls. In
      addition, levels of synaptophysin and spinophilin, proteins generally enriched in
      synapses and dendritic spines respectively, were elevated in the MPOA of maters.
      Dendritic morphology was also assessed in Golgi-impregnated brains of
      orchidectomized B6D2F1 males, and hybrid maters exhibited greater dendritic spine
      density in MPOA neurons. In sum, we show for the first time that retention of MSB
      in the absence of steroids is correlated with morphological differences in
      neurons.

PMID- 23874982
TI  - 4-1BB signaling activates the t cell factor 1 effector/beta-catenin pathway with
      delayed kinetics via ERK signaling and delayed PI3K/AKT activation to promote the
      proliferation of CD8+ T Cells.
AB  - 4-1BB (CD137), an inducible costimulatory molecule, strongly enhances the
      proliferation and effector function of CD8(+) T cells. Since the serine/threonine
      kinase, glycogen synthase kinase-3 (GSK-3), is involved in a variety of signaling
      pathways of cellular proliferation, migration, immune responses, and apoptosis,
      we examined whether 4-1BB signaling activates GSK-3/beta-catenin signaling and
      downstream transcription factors to enhance the proliferation of CD8(+) T cells.
      4-1BB signaling induces rapid activation of ERK and IkappaB degradation, and
      shows delayed activation of AKT at 24 h post 4-1BB stimulation on anti-CD3
      activated T cells. ERK and AKT signals were required for sustained beta-catenin
      levels by inactivating GSK-3, which was also observed with delayed kinetics after
      4-1BB stimulation. As a transcriptional partner of beta-catenin, 4-1BB signaling
      decreased levels of FOXO1 and increased levels of stimulatory TCF1 in CD8(+) T
      cells at 2-3 days but not at early time points after 4-1BB engagement. The
      enhanced proliferation of CD8(+) T cells due to 4-1BB signaling was completely
      abolished by treatment with the TCF1/beta-catenin inhibitor quercetin. These
      results show that 4-1BB signaling enhances the proliferation of activated CD8(+)
      T cells by activating the TCF1/beta-catenin axis via the PI3K/AKT/ERK pathway. As
      effects of 4-1BB on AKT, FOXO1, beta-catenin and GSK-3beta showed delayed
      kinetics it is likely that an intervening molecule induced by 4-1BB and ERK
      signaling in activated T cells is responsible for these effects. These effects
      were observed on CD8(+) but not on CD4(+) T cells. Moreover, 4-1BB appeared to be
      unique among several TNFRs tested in inducing increase in stimulatory over
      inhibitory TCF-1. 

PMID- 23874983
TI  - Extreme differences in forest degradation in Borneo: comparing practices in
      Sarawak, Sabah, and Brunei.
AB  - The Malaysian states of Sabah and Sarawak are global hotspots of forest loss and
      degradation due to timber and oil palm industries; however, the rates and
      patterns of change have remained poorly measured by conventional field or
      satellite approaches. Using 30 m resolution optical imagery acquired since 1990,
      forest cover and logging roads were mapped throughout Malaysian Borneo and Brunei
      using the Carnegie Landsat Analysis System. We uncovered ~364,000 km of roads
      constructed through the forests of this region. We estimated that in 2009 there
      were at most 45,400 km(2) of intact forest ecosystems in Malaysian Borneo and
      Brunei. Critically, we found that nearly 80% of the land surface of Sabah and
      Sarawak was impacted by previously undocumented, high-impact logging or clearing
      operations from 1990 to 2009. This contrasted strongly with neighbouring Brunei,
      where 54% of the land area remained covered by unlogged forest. Overall, only 8%
      and 3% of land area in Sabah and Sarawak, respectively, was covered by intact
      forests under designated protected areas. Our assessment shows that very few
      forest ecosystems remain intact in Sabah or Sarawak, but that Brunei, by largely
      excluding industrial logging from its borders, has been comparatively successful
      in protecting its forests. 

PMID- 23874984
TI  - The role of apelin in the retina of diabetic rats.
AB  - PURPOSE: Apelin is a novel adipocytokine participating in diabetes, but its role
      in diabetic retinopathy (DR) is unknown. Our study aimed to investigate the
      effect of apelin on the proliferative potential in DR along with its antagonist
      inhibitory effects. PRINCIPAL FINDINGS: Strong staining of apelin, co-localized
      with glial fibrillary acidic protein (GFAP) and vascular endothelial growth
      factor (VEGF) was observed in the retina of diabetic rats. Apelin, GFAP, and VEGF
      mRNA and protein levels were significantly increased in the sample's retinas.
      Moreover, exogenous apelin promoted retinal Muller cell proliferation in vivo.
      Simultaneously, apelin induced GFAP and VEGF expression. F13A markedly reduced
      retinal gliosis caused by diabetes. Furthermore, F13A suppressed both GFAP and
      VEGF expression in vivo. SIGNIFICANCE: Our results strongly suggest that apelin
      is associated with the development of DR and contributes to changes in the
      retinas of diabetic rats. Apelin induced promotion of cell proliferation lends
      support to the possibility that apelin may play a role in the progression of DR
      to a proliferative phase. This possible role deserves further investigation,
      which may offer new perspectives in the early prevention and treatment of DR.

PMID- 23874985
TI  - Evaluating total lymphocyte count as a surrogate marker for CD4 cell count in the
      management of HIV-infected patients in resource-limited settings: a study from
      China.
AB  - OBJECTIVE: To evaluate the correlation of total lymphocyte count (TLC) and CD4
      cell count and the suitability of TLC as a surrogate marker for CD4 cell count of
      HIV-infected patients in China. METHODS: Usefulness of TLC as a surrogate marker
      for a CD4 cell count <350 cells/mm(3) for HIV-positive patients in China was
      evaluated by 977 pairs of TLC and CD4 cell count from 977 outpatients. The result
      was then validated by a literature review which was conducted on 9 relevant
      articles. Further investigation using the 977 pairs of TLC and CD4 cell count
      data was done to determine a TLC threshold for predicting a CD4 cell count <500
      cells/mm(3). Correlation and receiver operating characteristic (ROC) analysis
      were performed for both CD4 cell counts, and the sensitivity and specificity were
      computed. RESULTS: Good correlation was noted between TLC and CD4 count (r =
      0.60, 95% CI, 0.56-0.64). TLC obtained a relatively high diagnostic performance
      (area under ROC curve, 0.80) for predicting a CD4 cell count <350 cells/mm(3),
      with a sensitivity of 0.65 (95% CI, 0.61-0.68) and a specificity of 0.80 (95% CI,
      0.75-0.85) at the TLC threshold of 1570 cells/mm(3). The literature review
      suggested that for a CD4 cell count <350 cells/mm(3), the optimal TLC threshold
      was 1500 cells/mm(3), which was similar to the figure presented in this
      observational study. As for predicting a CD4 cell count <500 cells/mm(3), TLC
      obtained a high diagnostic performance (area under ROC curve, 0.82) as well with
      a sensitivity of 0.70 (95% CI, 0.67-0.73) and a specificity of 0.80 (95% CI, 0.73
      0.87). CONCLUSIONS: When considering the antiretroviral therapy for HIV-infected
      Chinese individuals, total lymphocyte count can be considered as an inexpensive
      and easily available surrogate marker for predicting two clinically important
      thresholds of CD4 count of 350 cells/mm(3) and 500 cells/mm(3).

PMID- 23874986
TI  - Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged
      mice without evident damage and then disseminates to mouse kidneys.
AB  - Ricin is a potent toxin found in the beans of Ricinus communis and is often
      lethal for animals and humans when aerosolized or injected and causes significant
      morbidity and occasional death when ingested. Ricin has been proposed as a
      bioweapon because of its lethal properties, environmental stability, and
      accessibility. In oral intoxication, the process by which the toxin transits
      across intestinal mucosa is not completely understood. To address this question,
      we assessed the impact of ricin on the gastrointestinal tract and organs of mice
      after dissemination of toxin from the gut. We first showed that ricin adhered in
      a specific pattern to human small bowel intestinal sections, the site within the
      mouse gut in which a variable degree of damage has been reported by others. We
      then monitored the movement of ricin across polarized human HCT-8 intestinal
      monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed
      that, in both systems, ricin trafficked through the cells without apparent damage
      until 24 hours post intoxication. We delivered a lethal dose of purified
      fluorescently-labeled ricin to mice by oral gavage and followed transit of the
      toxin from the gastrointestinal tracts to the internal organs by in vivo imaging
      of whole animals over time and ex vivo imaging of organs at various time points.
      In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed
      them for the presence of ricin and for histological damage. Finally, we compared
      serum chemistry values from buffer-treated versus ricin-intoxicated animals. We
      conclude that ricin transverses human intestinal cells and mouse intestinal cells
      in situ prior to any indication of enterocyte damage and that ricin rapidly
      reaches the kidneys of intoxicated mice. We also propose that mice intoxicated
      orally with ricin likely die from distributive shock. 

PMID- 23874987
TI  - Identification and characterization of two novel viruses in ocular infections in
      reindeer.
AB  - A thorough understanding of virus diversity in wildlife provides epidemiological
      baseline information about pathogens. In this study, eye swab samples were
      obtained from semi-domesticated reindeer (Rangifertarandus tarandus) in Norway
      during an outbreak of infectious eye disease, possibly a very early stage of
      infectious keratoconjunctivitis (IKC). Large scale molecular virus screening,
      based on host nucleic acid depletion, sequence-independent amplification and next
      generation sequencing of partially purified viral nucleic acid, revealed the
      presence of a new papillomavirus in 2 out of 8 eye swab samples and a new
      betaherpesvirus in 3 out of 8 eye swab samples collected from animals with
      clinical signs and not in similar samples in 9 animals without clinical signs.
      Whether either virus was responsible for causing the clinical signs or in any
      respect was associated to the disease condition remains to be determined. 

PMID- 23874988
TI  - Selective inhibition by ethanol of mitochondrial calcium influx mediated by
      uncoupling protein-2 in relation to N-methyl-D-aspartate cytotoxicity in cultured
      neurons.
AB  - BACKGROUND: We have shown the involvement of mitochondrial uncoupling protein-2
      (UCP2) in the cytotoxicity by N-methyl-D-aspartate receptor (NMDAR) through a
      mechanism relevant to the increased mitochondrial Ca(2+) levels in HEK293 cells
      with acquired NMDAR channels. Here, we evaluated pharmacological profiles of
      ethanol on the NMDA-induced increase in mitochondrial Ca(2+) levels in cultured
      murine neocortical neurons. METHODOLOGY/PRINCIPAL FINDINGS: In neurons exposed to
      glutamate or NMDA, a significant increase was seen in mitochondrial Ca(2+) levels
      determined by Rhod-2 at concentrations of 0.1 to 100 uM. Further addition of 250
      mM ethanol significantly inhibited the increase by glutamate and NMDA in Rhod-2
      fluorescence, while similarly potent inhibition of the NMDA-induced increase was
      seen after exposure to ethanol at 50 to 250 mM in cultured neurons. Lentiviral
      overexpression of UCP2 significantly accelerated the increase by NMDA in Rhod-2
      fluorescence in neurons, without affecting Fluo-3 fluorescence for intracellular
      Ca(2+) levels. In neurons overexpressing UCP2, exposure to ethanol resulted in
      significantly more effective inhibition of the NMDA-induced increase in
      mitochondrial free Ca(2+) levels than in those without UCP2 overexpression,
      despite a similarly efficient increase in intracellular Ca(2+) levels
      irrespective of UCP2 overexpression. Overexpression of UCP2 significantly
      increased the number of dead cells in a manner prevented by ethanol in neurons
      exposed to glutamate. In HEK293 cells with NMDAR containing GluN2B subunit, more
      efficient inhibition was similarly induced by ethanol at 50 and 250 mM on the
      NMDA-induced increase in mitochondrial Ca(2+) levels than in those with GluN2A
      subunit. Decreased protein levels of GluN2B, but not GluN2A, subunit were seen in
      immunoprecipitates with UCP2 from neurons with brief exposure to ethanol at
      concentrations over 50 mM. CONCLUSIONS/SIGNIFICANCE: Ethanol could inhibit the
      interaction between UCP2 and NMDAR channels to prevent the mitochondrial Ca(2+)
      incorporation and cell death after NMDAR activation in neurons.

PMID- 23874989
TI  - Inferring potential microRNA-microRNA associations based on targeting propensity
      and connectivity in the context of protein interaction network.
AB  - MicroRNAs (miRNAs) are a group of small non-coding RNAs that play important
      regulatory roles at the post-transcriptional level. Although several
      computational methods have been developed to compare miRNAs, it is still a
      challenging and a badly needed task with the availability of various biological
      data resources. In this study, we proposed a novel graph theoretic property based
      computational framework and method, called miRFunSim, for quantifying the
      associations between miRNAs based on miRNAs targeting propensity and proteins
      connectivity in the integrated protein-protein interaction network. To evaluate
      the performance of our method, we applied the miRFunSim method to compute
      functional similarity scores of miRNA pairs between 100 miRNAs whose target genes
      have been experimentally supported and found that the functional similarity
      scores of miRNAs in the same family or in the same cluster are significantly
      higher compared with other miRNAs which are consistent with prior knowledge.
      Further validation analysis on experimentally verified miRNA-disease associations
      suggested that miRFunSim can effectively recover the known miRNA pairs associated
      with the same disease and achieve a higher AUC of 83.1%. In comparison with
      similar methods, our miRFunSim method can achieve more effective and more
      reliable performance for measuring the associations of miRNAs. We also conducted
      the case study examining liver cancer based on our method, and succeeded in
      uncovering the candidate liver cancer related miRNAs such as miR-34 which also
      has been proven in the latest study. 

PMID- 23874990
TI  - Sex difference in cue strategy in a modified version of the Morris water task:
      correlations between brain and behaviour.
AB  - BACKGROUND: Sex differences in spatial memory function have been reported with
      mixed results in the literature, with some studies showing male advantages and
      others showing no differences. When considering estrus cycle in females, results
      are mixed at to whether high or low circulating estradiol results in an advantage
      in spatial navigation tasks. Research involving humans and rodents has
      demonstrated males preferentially employ Euclidean strategies and utilize
      geometric cues in order to spatially navigate, whereas females employ landmark
      strategies and cues in order to spatially navigate. METHODOLOGY/PRINCIPAL
      FINDINGS: This study used the water-based snowcone maze in order to assess male
      and female preference for landmark or geometric cues, with specific emphasis
      placed on the effects of estrus cycle phase for female rat. Performance and
      preference for the geometric cue was examined in relation to total hippocampal
      and hippocampal subregions (CA1&2, CA3 and dentate gyrus) volumes and entorhinal
      cortex thickness in order to determine the relation between strategy and spatial
      performance and brain area size. The study revealed that males outperformed
      females overall during training trials, relied on the geometric cue when the
      platform was moved and showed significant correlations between entorhinal cortex
      thickness and spatial memory performance. No gross differences in behavioural
      performance was observed within females when accounting for cyclicity, and only
      total hippocampal volume was correlated with performance during the learning
      trials. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the sex-specific use of
      cues and brain areas in a spatial learning task.

PMID- 23874991
TI  - Are platelet-rich products necessary during the arthroscopic repair of full
      thickness rotator cuff tears: a meta-analysis.
AB  - BACKGROUND: Platelet-rich products (PRP) are widely used for rotator cuff tears.
      However, whether platelet-rich products produce superior clinical or radiological
      outcomes is controversial. This study aims to use meta-analysis to compare
      clinical and radiological outcomes between groups with or without platelet-rich
      products. METHODS: The Pubmed, Embase, and Cochrane library databases were
      searched for relevant studies published before April 20, 2013. Studies were
      selected that clearly reported a comparison between the use or not of platelet
      rich products. The Constant, ASES, UCLA, and SST scale systems and the rotator
      cuff retear rate were evaluated. The weighted mean differences and relative risks
      were calculated using a fixed-effects model. RESULTS: Seven studies were enrolled
      in this meta-analysis. No significant differences were found for the Constant
      scale (0.73, 95% CI, -1.82 to 3.27, P=0.58), ASES scale (-2.89, 95% CI, -6.31 to
      0.53, P=0.1), UCLA scale (-0.79, 95% CI, -2.20 to 0.63, P=0.28), SST scale (0.34,
      95% CI, -0.01 to 0.69, P=0.05), and the overall rotator cuff retear rate (0.71,
      95% CI, 0.48 to 1.05, P=0.08). Subgroup analysis according to the initial tear
      size showed a lower retear rate in small- and medium-sized tears (0.33, 95% CI,
      0.12 to 0.91, P=0.03) after platelet-rich product application but no difference
      for large- and massive-sized tears (0.86, 95% CI, 0.60 to 1.23, P=0.42).
      CONCLUSION: In conclusion, the meta-analysis suggests that the platelet-rich
      products have no benefits on the overall clinical outcomes and retear rate for
      the arthroscopic repair of full-thickness rotator cuff tears. However, a decrease
      occurred in the rate of retears among patients treated with PRP for small- and
      medium-sized rotator cuff tears but not for large- and massive-sized tears. LEVEL
      OF EVIDENCE: Level II.

PMID- 23874992
TI  - Effects of external potassium (k) supply on drought tolerances of two contrasting
      winter wheat cultivars.
AB  - BACKGROUND: Drought is a common stress limiting crops growth and productivities
      worldwide. Water deficit may increase cellular membrane permeability, resulting
      in K outflow. Internal K starvation may disorder plant metabolism and limit plant
      growth. However, it is seldom reported about the effects of external K on drought
      tolerance of contrasting wheat cultivars. METHODOLOGY/PRINCIPAL FINDINGS: A
      hydroponics experiment was carried out in a non-controlled greenhouse. Seedlings
      of drought-tolerant SN16 and intolerant JM22 were simultaneously treated by five
      levels of K2CO3 (0, 2.5, 5, 7.5, 10 mM) and two levels of PEG6000 (0, 20%) for 7
      days. External K2CO3 significantly increased shoot K(+) content, water potential,
      chlorophyll content as well as gas exchange, but decreased electrolyte leakage
      (EL) and MDA content in both cultivars under PEG6000 stress. Antioxidant enzymes
      activities were up-regulated by PEG6000 while external K2CO3 reduced those
      changes. Molecular basis was explained by measuring the expression levels of
      antioxidant enzymes related genes. Shoot and root biomass were also increased by
      K2CO3 supply under drought stress. Although adequate K2CO3 application enhanced
      plant growth for both cultivars under drought stress, SN16 was better than JM22
      due to its high drought tolerance. CONCLUSIONS/SIGNIFICANCE: Adequate external K
      may effectively protect winter wheat from drought injuries. We conclude that
      drought-tolerant wheat combined with adequate external K supply may be a
      promising strategy for better growth in arid and semi-arid regions.

PMID- 23874993
TI  - Omega-3 eicosapentaenoic acid decreases CD133 colon cancer stem-like cell marker
      expression while increasing sensitivity to chemotherapy.
AB  - Colorectal cancer is the third leading cause of cancer-related death in the
      western world. In vitro and in vivo experiments showed that omega-3
      polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer
      cells, including colon cancer, and increase the efficacy of various anticancer
      drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the
      tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs)
      that are responsible for tumor formation and maintenance. CSLCs have also been
      linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon
      CSLCs have been immunophenotyped using several antibodies against cellular
      markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to
      isolate a population of colon cancer cells that retains stem cells properties
      (CSLCs) from both established cell lines and primary cell cultures. We
      demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively
      incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased
      the cell number of the overall population of cancer cells, but not of the CD133
      (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression
      and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20
      (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the
      sensitivity of COLO 320 DM cells (total population) to both standard-of-care
      chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the
      sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil. 

PMID- 23874994
TI  - Sporulation genes associated with sporulation efficiency in natural isolates of
      yeast.
AB  - Yeast sporulation efficiency is a quantitative trait and is known to vary among
      experimental populations and natural isolates. Some studies have uncovered the
      genetic basis of this variation and have identified the role of sporulation genes
      (IME1, RME1) and sporulation-associated genes (FKH2, PMS1, RAS2, RSF1, SWS2), as
      well as non-sporulation pathway genes (MKT1, TAO3) in maintaining this variation.
      However, these studies have been done mostly in experimental populations.
      Sporulation is a response to nutrient deprivation. Unlike laboratory strains,
      natural isolates have likely undergone multiple selections for quick adaptation
      to varying nutrient conditions. As a result, sporulation efficiency in natural
      isolates may have different genetic factors contributing to phenotypic variation.
      Using Saccharomyces cerevisiae strains in the genetically and environmentally
      diverse SGRP collection, we have identified genetic loci associated with
      sporulation efficiency variation in a set of sporulation and sporulation
      associated genes. Using two independent methods for association mapping and
      correcting for population structure biases, our analysis identified two linked
      clusters containing 4 non-synonymous mutations in genes - HOS4, MCK1, SET3, and
      SPO74. Five regulatory polymorphisms in five genes such as MLS1 and CDC10 were
      also identified as putative candidates. Our results provide candidate genes
      contributing to phenotypic variation in the sporulation efficiency of natural
      isolates of yeast. 

PMID- 23874997
TI  - Shift in black rhinoceros diet in the presence of elephant: evidence for
      competition?
AB  - In African large herbivore assemblages, megaherbivores dominate the biomass and
      utilise the greatest share of available resources. Consequently, they are
      considered a separate trophic guild that structures the food niches of coexisting
      large herbivores. However, there exists little empirical evidence on how food
      resources are shared within this guild, and none for direct competition for food
      between megaherbivores. Using the histological analysis of faeces, we explore
      this phenomenon for African elephant Loxodonta africana and black rhinoceros
      Diceros bicornis in the Addo Elephant National Park, South Africa, where the
      accumulated impacts of elephant have reduced browse availability. Despite being
      unable to generalise beyond our study sites, our observations support the
      predictions of competition theory (as opposed to optimality theory) by showing
      (1) a clear seasonal separation in resource use between these megaherbivores that
      increased as resource availability declined, and (2) rhinoceros changed their
      selectivity in the absence of elephant (using an adjacent site) by expanding and
      shifting their diet along the grass-browse continuum, and in relation to
      availability. Although black rhinoceros are generally considered strict browsers,
      the most significant shift in diet occurred as rhinoceros increased their
      preferences for grasses in the presence of elephant. We speculate that the lack
      of specialised grazing adaptations may increase foraging costs in rhinoceros,
      through reduced harvest- and handling-efficiencies of grasses. In the short-term,
      this may be off-set by an enhanced tolerance for low quality food and by
      seasonally mobilising fat reserves; however, the long-term fitness consequences
      require further study. Our data suggest that managing elephant at high densities
      may compromise the foraging opportunities of coexisting browsers. This may be
      particularly important in small, fenced areas and overlapping preferred habitats
      where impacts intensify. 

PMID- 23874995
TI  - Hippocampal gene expression meta-analysis identifies aging and age-associated
      spatial learning impairment (ASLI) genes and pathways.
AB  - A number of gene expression microarray studies have been carried out in the past,
      which studied aging and age-associated spatial learning impairment (ASLI) in the
      hippocampus in animal models, with varying results. Data from such studies were
      never integrated to identify the most significant ASLI genes and to understand
      their effect. In this study we integrated these data involving rats using meta
      analysis. Our results show that proper removal of batch effects from microarray
      data generated from different laboratories is necessary before integrating them
      for meta-analysis. Our meta-analysis has identified a number of significant
      differentially expressed genes across age or across ASLI. These genes affect many
      key functions in the aged compared to the young rats, which include viability of
      neurons, cell-to-cell signalling and interaction, migration of cells, neuronal
      growth, and synaptic plasticity. These functional changes due to the altered gene
      expression may manifest into various neurodegenerative diseases and disorders,
      some of which leading into syndromic memory impairments. While other aging
      related molecular changes can result into altered synaptic plasticity simply
      causing normal aging related non-syndromic learning or spatial learning
      impairments such as ASLI. 

PMID- 23874996
TI  - Bacteriophage receptor binding protein based assays for the simultaneous
      detection of Campylobacter jejuni and Campylobacter coli.
AB  - Campylobacter jejuni and Campylobacter coli are the most common bacterial causes
      of foodborne gastroenteritis which is occasionally followed by a debilitating
      neuropathy known as Guillain-Barre syndrome. Rapid and specific detection of
      these pathogens is very important for effective control and quick treatment of
      infection. Most of the diagnostics available for these organisms are time
      consuming and require technical expertise with expensive instruments and reagents
      to perform. Bacteriophages bind to their host specifically through their receptor
      binding proteins (RBPs), which can be exploited for pathogen detection. We
      recently sequenced the genome of C. jejuni phage NCTC12673 and identified its
      putative host receptor binding protein, Gp047. In the current study, we localized
      the receptor binding domain to the C-terminal quarter of Gp047. CC-Gp047 could be
      produced recombinantly and was capable of agglutinating both C. jejuni and C.
      coli cells unlike the host range of the parent phage which is limited to a subset
      of C. jejuni isolates. The agglutination procedure could be performed within
      minutes on a glass slide at room temperature and was not hindered by the presence
      of buffers or nutrient media. This agglutination assay showed 100% specificity
      and the sensitivity was 95% for C. jejuni (n = 40) and 90% for C. coli (n = 19).
      CC-Gp047 was also expressed as a fusion with enhanced green fluorescent protein
      (EGFP). Chimeric EGFP_CC-Gp047 was able to specifically label C. jejuni and C.
      coli cells in mixed cultures allowing for the detection of these pathogens by
      fluorescent microscopy. This study describes a simple and rapid method for the
      detection of C. jejuni and C. coli using engineered phage RBPs and offers a
      promising new diagnostics platform for healthcare and surveillance laboratories. 

PMID- 23874998
TI  - Comparison of platelet ultrastructure and elastic properties in thrombo-embolic
      ischemic stroke and smoking using atomic force and scanning electron microscopy.
AB  - Thrombo-embolic ischemic stroke is a serious and debilitating disease, and it
      remains the second most common cause of death worldwide. Tobacco smoke exposure
      continues to be responsible for preventable deaths around the world, and is a
      major risk factor for stroke. Platelets play a fundamental role in clotting, and
      their pathophysiological functioning is present in smokers and stroke patients,
      resulting in a pro-thrombotic state. In the current manuscript, atomic force and
      scanning electron microscopy were used to compare the platelets of smokers,
      stroke patients and healthy individuals. Results showed that the elastic modulus
      of stroke platelets is decreased by up to 40%, whereas there is an elasticity
      decrease of up to 20% in smokers' platelets. This indicates a biophysical
      alteration of the platelets. Ultrastructurally, both the stroke patients and
      smokers' platelets are more activated than the healthy control group, with
      prominent cytoskeletal rearrangement involved; but to a more severe extent in the
      stroke group than in the smokers. Importantly, this is a confirmation of the
      extent of smoking as risk factor for stroke. We conclude by suggesting that the
      combined AFM and SEM analyses of platelets might give valuable information about
      the disease status of patients. Efficacy of treatment regimes on the integrity,
      cell shape, roughness and health status of platelets may be tracked, as this
      cell's health status is crucial in the over-activated coagulation system of
      conditions like stroke. 

PMID- 23874999
TI  - Improving precision of proximity ligation assay by amplified single molecule
      detection.
AB  - Proximity ligation assay (PLA) has been proven to be a robust protein detection
      method. The technique is characterized by high sensitivity and specificity, but
      the assay precision is probably limited by the PCR readout. To investigate this
      potential limitation and to improve precision, we developed a digital proximity
      ligation assay for protein measurement in fluids based on amplified single
      molecule detection. The assay showed significant improvements in precision, and
      thereby also detection sensitivity, over the conventional real-time PCR readout. 

PMID- 23875000
TI  - The taxonomy statistic uncovers novel clinical patterns in a population of
      ischemic stroke patients.
AB  - In this paper, we describe a simple taxonomic approach for clinical data mining
      elaborated by Marczewski and Steinhaus (M-S), whose performance equals the
      advanced statistical methodology known as the expectation-maximization (E-M)
      algorithm. We tested these two methods on a cohort of ischemic stroke patients.
      The comparison of both methods revealed strong agreement. Direct agreement
      between M-S and E-M classifications reached 83%, while Cohen's coefficient of
      agreement was kappa = 0.766(P < 0.0001). The statistical analysis conducted and
      the outcomes obtained in this paper revealed novel clinical patterns in ischemic
      stroke patients. The aim of the study was to evaluate the clinical usefulness of
      Marczewski-Steinhaus' taxonomic approach as a tool for the detection of novel
      patterns of data in ischemic stroke patients and the prediction of disease
      outcome. In terms of the identification of fairly frequent types of stroke
      patients using their age, National Institutes of Health Stroke Scale (NIHSS), and
      diabetes mellitus (DM) status, when dealing with rough characteristics of
      patients, four particular types of patients are recognized, which cannot be
      identified by means of routine clinical methods. Following the obtained
      taxonomical outcomes, the strong correlation between the health status at moment
      of admission to emergency department (ED) and the subsequent recovery of patients
      is established. Moreover, popularization and simplification of the ideas of
      advanced mathematicians may provide an unconventional explorative platform for
      clinical problems. 

PMID- 23875001
TI  - Urine scent marking (USM): a novel test for depressive-like behavior and a
      predictor of stress resiliency in mice.
AB  - Decreased interest in pleasurable stimuli including social withdrawal and reduced
      libido are some of the key symptomatic criteria for major depression, and thus
      assays that measure social and sexual behavior in rodents may be highly
      appropriate for modeling depressive states. Here we present a novel approach for
      validating rodent models of depression by assessing male urine scent marking
      (USM) made in consequence to a spot of urine from a proestrous female. USM is an
      ethologically important form of sexual communication expressed by males to
      attract females. The expression of this behavior is highly sensitive and adaptive
      to environmental cues and social status. We hypothesized that male USM behavior
      offers a naturalistic measure of social motivation that can be used to evaluate
      hedonic behaviors relevant to the study of mood disorders. We demonstrated that
      1) adult male mice displayed a strong preference for marking proestrous female
      urine with a high degree of specificity, 2) exposure to chronic social defeat
      profoundly decreased USM whereas exposure to environmental enrichment increased
      USM, 3) the standard antidepressant fluoxetine reversed declines in USM induced
      by social defeat, 4) USM behavior closely correlated with other hedonic measures,
      and 5) USM scores in non-stressed mice predicted behavioral outcomes after defeat
      exposure such that mice displaying high preference for marking female urine prior
      to social defeat showed behavioral resiliency after social defeat. The findings
      indicate that the USM test is a sensitive, validated measure of psychosocial
      stress effects that has high predictive value for examination of stress
      resiliency and vulnerability and their neurobiological substrates. 

PMID- 23875002
TI  - Failure of manganese to protect from Shiga toxin.
AB  - Shiga toxin (Stx), the main virulence factor of Shiga toxin producing Escherichia
      coli, is a major public health threat, causing hemorrhagic colitis and hemolytic
      uremic syndrome. Currently, there are no approved therapeutics for these
      infections; however manganese has been reported to provide protection from the
      Stx1 variant isolated from Shigella dysenteriae (Stx1-S) both in vitro and in
      vivo. We investigated the efficacy of manganese protection from Stx1-S and the
      more potent Stx2a isoform, using experimental systems well-established for
      studying Stx: in vitro responses of Vero monkey kidney cells, and in vivo
      toxicity to CD-1 outbred mice. Manganese treatment at the reported therapeutic
      concentration was toxic to Vero cells in culture and to CD-1 mice. At lower
      manganese concentrations that were better tolerated, we observed no protection
      from Stx1-S or Stx2a toxicity. The ability of manganese to prevent the effects of
      Stx may be particular to certain cell lines, mouse strains, or may only be
      manifested at high, potentially toxic manganese concentrations. 

PMID- 23875004
TI  - Is ritonavir-boosted atazanavir a risk for cholelithiasis compared to other
      protease inhibitors?
AB  - OBJECTIVE: To compare the incidence of complicated cholelithiasis in patients
      receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy
      with those on other protease inhibitors (PIs). DESIGN: We conducted a single
      center retrospective cohort study of patients who started either ritonavir
      boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted
      fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing
      antiretroviral therapy. METHODS: The incidence of complicated cholelithiasis was
      determined in each group. Complicated cholelithiasis was defined as follows: 1)
      cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2)
      symptomatic cholelithiasis or choledocholithiasis which required invasive
      procedures such as cholecystomy and endoscopic retrograde
      cholangiopancreatography. The effects of ATV/r were estimated by univariate and
      multivariate Cox hazards models as the primary exposure. RESULTS: Complicated
      cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the
      ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group
      (n = 776), respectively. The incidence was not statistically different in the two
      groups by log-rank test (P = 0.702). By univariate and multivariate analysis
      adjusted for age and body weight, ATV/r use was not associated with
      cholelithiasis. (HR = 1.365; 95% CI, 0.275-6.775; p = 0.704) (adjusted HR =
      1.390; 95% CI, 0.276-7.017; p = 0.690). For the 3 patients who developed
      cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis
      was 18, 34, and 39 months, respectively. CONCLUSION: In this study, the incidence
      of complicated cholelithiasis was low and was not different between patients on
      ATV/r and those on other PIs. On the contrary to ATV/r-associated
      nephrolithiasis, the possible risk of cholelithiasis should not preclude the use
      of ATV/r.

PMID- 23875003
TI  - Age-dependent modulation of synaptic plasticity and insulin mimetic effect of
      lipoic acid on a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease is a progressive neurodegenerative disease that entails
      impairments of memory, thinking and behavior and culminates into brain atrophy.
      Impaired glucose uptake (accumulating into energy deficits) and synaptic
      plasticity have been shown to be affected in the early stages of Alzheimer's
      disease. This study examines the ability of lipoic acid to increase brain glucose
      uptake and lead to improvements in synaptic plasticity on a triple transgenic
      mouse model of Alzheimer's disease (3xTg-AD) that shows progression of pathology
      as a function of age; two age groups: 6 months (young) and 12 months (old) were
      used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for
      4 weeks showed an insulin mimetic effect that consisted of increased brain
      glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt
      signaling pathway. Lipoic acid supplementation led to important changes in
      synaptic function as shown by increased input/output (I/O) and long term
      potentiation (LTP) (measured by electrophysiology). Lipoic acid was more
      effective in stimulating an insulin-like effect and reversing the impaired
      synaptic plasticity in the old mice, wherein the impairment of insulin signaling
      and synaptic plasticity was more pronounced than those in young mice. 

PMID- 23875006
TI  - Self Inflicted Injuries among Children in United States - estimates from a
      nationwide emergency department sample.
AB  - OBJECTIVE: The objectives of the current study are to provide nationally
      representative estimates of hospital based emergency department visits (ED)
      attributed to self inflicted injuries and attempted suicides among children in
      United States; and to identify potential methods of such intentional self
      inflicted injuries and attempted suicides. METHODS: The Nationwide Emergency
      Department Sample (year 2007) was used. All ED visits occurring among children
      (aged <=18 years) with an External Cause of Injury for any of self inflicted
      injuries were selected. Outcomes examined include hospital ED charges and
      hospitalization charges. All estimates were projected to national levels.
      RESULTS: 77,420 visits to hospital based emergency departments were attributed to
      self inflicted injuries among children (26,045 males and 51,370 females). The
      average age of the ED visits was 15.7 years. 134 patients died in ED's (106 males
      and 28 females) and 93 died in hospitals following in-patient admission (75 males
      and 18 females). A greater proportion of male ED visits were discharged routinely
      as opposed to female ED visits (51.1% versus 44%). A greater proportion of male
      ED visits also died in the emergency departments compared to female visits (0.4%
      versus 0.05%). 17,965 ED visits necessitated admission into same hospital. The
      mean charge for each ED visit was $1,874. Self inflicted injuries by poisoning
      were the most frequently reported sources accounting for close to 70% of all ED
      visits. CONCLUSIONS: Females comprise a greater proportion of ED visits
      attributed to self inflicted injuries. 227 children died either in the ED's or in
      hospitals. The current study results highlight the burden associated with such
      injuries among children.

PMID- 23875005
TI  - Racial disparities in the use of cardiac revascularization: does local hospital
      capacity matter?
AB  - OBJECTIVE: To assess the extent to which the observed racial disparities in
      cardiac revascularization use can be explained by the variation across counties
      where patients live, and how the within-county racial disparities is associated
      with the local hospital capacity. DATA SOURCES: Administrative data from
      Pennsylvania Health Care Cost Containment Council (PHC4) between 1995 and 2006.
      STUDY DESIGN: The study sample included 207,570 Medicare patients admitted to
      hospital for acute myocardial infarction (AMI). We identified the use of coronary
      artery bypass graft (CABG) and percutaneous coronary intervention (PCI)
      procedures within three months after the patient's initial admission for AMI.
      Multi-level hierarchical models were used to determine the extent to which racial
      disparities in procedure use were attributable to the variation in local hospital
      capacity. PRINCIPAL FINDINGS: Blacks were less likely than whites to receive CABG
      (9.1% vs. 5.8%; p<0.001) and PCI (15.7% vs. 14.2%; p<0.001). The state-level
      racial disparity in use rate decreases for CABG, and increases for PCI, with the
      county adjustment. Higher number of revascularization hospitals per 1,000 AMI
      patients was associated with smaller within-county racial differences in CABG and
      PCI rates. Meanwhile, very low capacity of catheterization suites and AMI
      hospitals contributed to significantly wider racial gap in PCI rate. CONCLUSIONS:
      County variation in cardiac revascularization use rates helps explain the
      observed racial disparities. While smaller hospital capacity is associated with
      lower procedure rates for both racial groups, the impact is found to be larger on
      blacks. Therefore, consequences of fewer medical resources may be particularly
      pronounced for blacks, compared with whites.

PMID- 23875008
TI  - Genome survey sequencing and genetic background characterization of
      Gracilariopsis lemaneiformis (Rhodophyta) based on next-generation sequencing.
AB  - Gracilariopsis lemaneiformis has a high economic value and is one of the most
      important aquaculture species in China. Despite it is economic importance, it has
      remained largely unstudied at the genomic level. In this study, we conducted a
      genome survey of Gp. lemaneiformis using next-generation sequencing (NGS)
      technologies. In total, 18.70 Gb of high-quality sequence data with an estimated
      genome size of 97 Mb were obtained by HiSeq 2000 sequencing for Gp.
      lemaneiformis. These reads were assembled into 160,390 contigs with a N50 length
      of 3.64 kb, which were further assembled into 125,685 scaffolds with a total
      length of 81.17 Mb. Genome analysis predicted 3490 genes and a GC% content of
      48%. The identified genes have an average transcript length of 1,429 bp, an
      average coding sequence size of 1,369 bp, 1.36 exons per gene, exon length of
      1,008 bp, and intron length of 191 bp. From the initial assembled scaffold,
      transposable elements constituted 54.64% (44.35 Mb) of the genome, and 7737
      simple sequence repeats (SSRs) were identified. Among these SSRs, the
      trinucleotide repeat type was the most abundant (up to 73.20% of total SSRs),
      followed by the di- (17.41%), tetra- (5.49%), hexa- (2.90%), and penta- (1.00%)
      nucleotide repeat type. These characteristics suggest that Gp. lemaneiformis is a
      model organism for genetic study. This is the first report of genome-wide
      characterization within this taxon. 

PMID- 23875007
TI  - Soluble markers of the Toll-like receptor 4 pathway differentiate between active
      and latent tuberculosis and are associated with treatment responses.
AB  - BACKGROUND: Biomarkers to differentiate between active tuberculosis (TB) and
      latent TB infection (LTBI) and to monitor treatment responses are requested to
      complement TB diagnostics and control, particularly in patients with multi-drug
      resistant TB. We have studied soluble markers of the Toll-like-receptor 4 (TLR-4)
      pathway in various stages of TB disease and during anti-TB treatment. METHODS:
      Plasma samples from patients with culture confirmed drug-sensitive TB (n = 19)
      were collected before and after 2, 8 and 24 weeks of efficient anti-TB treatment
      and in a LTBI group (n = 6). Soluble (s) CD14 and myeloid differentiation-2 (MD
      2) were analyzed by the Enzyme-linked immunosorbent assay (ELISA).
      Lipopolysaccharide (LPS) was analyzed by the Limulus Amebocyte Lysate
      colorimetric assay. Nonparametric statistics were applied. RESULTS: Plasma levels
      of sCD14 (p<0.001), MD-2 (p = 0.036) and LPS (p = 0.069) were elevated at
      baseline in patients with untreated active TB compared to the LTBI group. MD-2
      concentrations decreased after 2 weeks of treatment (p = 0.011), while LPS levels
      decreased after 8 weeks (p = 0.005). In contrast, sCD14 levels increased after 2
      weeks (p = 0.047) with a subsequent modest decrease throughout the treatment
      period. There was no significant difference in concentrations of any of these
      markers between patients with pulmonary and extrapulmonary TB or between patients
      with or without symptoms. CONCLUSION: Our data suggest that plasma levels of LPS,
      MD-2 and sCD14 can discriminate between active TB and LTBI. A decline in LPS and
      MD-2 concentrations was associated with response to anti-TB treatment. The
      clinical potential of these soluble TLR-4 pathway proteins needs to be further
      explored.

PMID- 23875009
TI  - Association between precipitation upstream of a drinking water utility and nurse
      advice calls relating to acute gastrointestinal illnesses.
AB  - BACKGROUND: The River Gota Alv is a source of fresh-water for the City of
      Gothenburg (Sweden). We recently identified a clear association between upstream
      precipitation and indicator bacteria concentrations in the river water outside
      the intake to the drinking water utility. This study aimed to determine if
      variation in the incidence of acute gastrointestinal illnesses is associated with
      upstream precipitation. METHODS: We acquired data, covering 1494 days, on the
      daily number of telephone calls to the nurse advice line from citizens in
      Gothenburg living in areas with Gota Alv as a fresh-water supply. We separated
      calls relating to gastrointestinal illnesses from other medical concerns, and
      analyzed their association with precipitation using a distributed lag non-linear
      Poisson regression model, adjusting for seasonal patterns and covariates. We used
      a 0-21-day lag period for precipitation to account for drinking water delivery
      times and incubation periods of waterborne pathogens. RESULTS: The study period
      contained 25,659 nurse advice calls relating to gastrointestinal illnesses. Heavy
      rainfall was associated with increased calls the same day and around 5-6 days
      later. Consecutive days of wet weather were also found to be associated with an
      increase in the daily number of gastrointestinal concerns. No associations were
      identified between precipitation and nurse advice calls relating to other medical
      concerns. CONCLUSION: An increase in nurse advice calls relating to
      gastrointestinal illnesses around 5-6 days after heavy rainfall is consistent
      with a hypothesis that the cause could be related to drinking water due to
      insufficient barriers in the drinking water production, suggesting the need for
      improved drinking water treatment.

PMID- 23875010
TI  - Tumefactive multiple sclerosis in Taiwan.
AB  - BACKGROUND: Multiple sclerosis (MS) is less common in Asia, including Taiwan, and
      some characteristics of MS in Asians differ from those of Caucasians. Tumefactive
      brain lesion is even rarer in MS patients. OBJECTIVE: To review patients with
      tumefactive MS and compare them with those in other studies investigating
      tumefactive demyelinating lesions and our Taiwanese typical MS patients. METHODS:
      Twelve patients (6.3%) from the 190 MS patients visiting Taipei Veterans General
      Hospital from 1985 to 2010 were enrolled. They all fulfilled the McDonald or
      Poser criteria for MS and had at least one brain lesion larger than 2 centimeters
      with or without a mass effect. RESULTS: Eleven patients (91.7%) were female and
      presented tumefactive brain lesions during the first attack. The clinical course
      of all patients was relapsing-remitting with a second attack within 2 years.
      Their initial extended disability status score was higher, but the prognosis was
      better after more than 2 years of follow-up, than in other studies. Moreover, our
      patients did not have optic or spinal involvement as well as positive
      neuromyelitis optica immunoglobulin or aquaporin-4 antibody, which is very common
      in Taiwanese MS patients. CONCLUSION: Tumefactive MS is not common in Taiwan.
      Although the tumefactive demyelinating lesions seem to be terrible initially,
      their prognosis is relatively more favorable than expected.

PMID- 23875011
TI  - Proline accumulation in leaves of Periploca sepium via both biosynthesis up
      regulation and transport during recovery from severe drought.
AB  - Drought resistance and recovery ability are two important requisites for plant
      adaptation to drought environments. Proline (Pro) metabolism has been a major
      concern in plant drought tolerance. However, roles of Pro metabolism in plant
      recovery ability from severe drought stress are largely unexplored. Periploca
      sepium Bunge has gained increasing attention for its adaptation to dry
      environments. Here, we investigated Pro metabolism in different tissues of P.
      sepium seedlings in the course of drought stress and recovery. We found that leaf
      Pro metabolism response during post-drought recovery was dependant on drought
      severity. Pro biosynthesis was down-regulated during recovery from -0.4 MPa but
      increased continually and notably during recovery from -1.0 MPa. Significant
      correlation between Pro concentration and Delta1-pyrroline-5-carboxylate
      synthetase activity indicates that Glutamate pathway is the predominant synthesis
      route during both drought and re-watering periods. Ornithine delta
      aminotransferase activity was up-regulated significantly only during recovery
      from -1.0 MPa, suggesting positive contribution of ornithine pathway to improving
      plant recovery capacity from severe drought. In addition to up-regulation of
      biosynthesis, Pro transport from stems and roots also contributed to high Pro
      accumulation in leaves and new buds during recovery from -1.0 MPa, as indicated
      by the combined analysis of Pro concentration and its biosynthesis in stems,
      roots and new buds. Except its known roles as energy, carbon and nitrogen sources
      for plant rapid recovery, significant positive correlation between Pro
      concentration and total antioxidant activity indicates that Pro accumulation can
      also promote plant damage repair ability by up-regulating antioxidant activity
      during recovery from severe drought stress. 

PMID- 23875012
TI  - Tracking fungal community responses to maize plants by DNA- and RNA-based
      pyrosequencing.
AB  - We assessed soil fungal diversity and community structure at two sampling times
      (t1 = 47 days and t2 = 104 days of plant age) in pots associated with four maize
      cultivars, including two genetically modified (GM) cultivars by high-throughput
      pyrosequencing of the 18S rRNA gene using DNA and RNA templates. We detected no
      significant differences in soil fungal diversity and community structure
      associated with different plant cultivars. However, DNA-based analyses yielded
      lower fungal OTU richness as compared to RNA-based analyses. Clear differences in
      fungal community structure were also observed in relation to sampling time and
      the nucleic acid pool targeted (DNA versus RNA). The most abundant soil fungi, as
      recovered by DNA-based methods, did not necessary represent the most "active"
      fungi (as recovered via RNA). Interestingly, RNA-derived community compositions
      at t1 were highly similar to DNA-derived communities at t2, based on
      presence/absence measures of OTUs. We recovered large proportions of fungal
      sequences belonging to arbuscular mycorrhizal fungi and Basidiomycota, especially
      at the RNA level, suggesting that these important and potentially beneficial
      fungi are not affected by the plant cultivars nor by GM traits (Bt toxin
      production). Our results suggest that even though DNA- and RNA-derived soil
      fungal communities can be very different at a given time, RNA composition may
      have a predictive power of fungal community development through time. 

PMID- 23875013
TI  - Incorporation of bone marrow cells in pancreatic pseudoislets improves
      posttransplant vascularization and endocrine function.
AB  - Failure of revascularization is known to be the major reason for the poor outcome
      of pancreatic islet transplantation. In this study, we analyzed whether
      pseudoislets composed of islet cells and bone marrow cells can improve
      vascularization and function of islet transplants. Pancreatic islets isolated
      from Syrian golden hamsters were dispersed into single cells for the generation
      of pseudoislets containing 4*10(3) cells. To create bone marrow cell-enriched
      pseudoislets 2*10(3) islet cells were co-cultured with 2*10(3) bone marrow cells.
      Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted
      syngeneically into skinfold chambers to study graft vascularization by intravital
      fluorescence microscopy. Native islet transplants served as controls. Bone marrow
      cell-enriched pseudoislets showed a significantly improved vascularization
      compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched
      pseudoislets but not pseudoislets normalized blood glucose levels after
      transplantation of 1000 islet equivalents under the kidney capsule of
      streptozotocin-induced diabetic animals, although the bone marrow cell-enriched
      pseudoislets contained only 50% of islet cells compared to pseudoislets and
      native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets
      composed of bone marrow cells from GFP-expressing mice showed a distinct fraction
      of cells expressing both GFP and insulin, indicating a differentiation of bone
      marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of
      pseudoislets by bone marrow cells enhances vascularization after transplantation
      and increases the amount of insulin-producing tissue. Accordingly, bone marrow
      cell-enriched pseudoislets may represent a novel approach to increase the success
      rate of islet transplantation. 

PMID- 23875014
TI  - Influence of land mosaic composition and structure on patchy populations: the
      case of the water vole (Arvicola sapidus) in Mediterranean farmland.
AB  - The ability of patchy populations to persist in human-dominated landscapes is
      often assessed using focal patch approaches, in which the local occurrence or
      abundance of a species is related to the properties of individual patches and the
      surrounding landscape context. However, useful additional insights could probably
      be gained through broader, mosaic-level approaches, whereby whole land mosaics
      with contrasting patch-network and matrix characteristics are the units of
      investigation. In this study we addressed this issue, analysing how the southern
      water vole (Arvicola sapidus) responds to variables describing patch-network and
      matrix properties within replicated Mediterranean farmland mosaics, across a
      gradient of agricultural intensification. Patch-network characteristics had a
      dominant effect, with the total amount of habitat positively influencing both the
      occurrence of water voles and the proportion of area occupied in land mosaics.
      The proportions of patches and area occupied by the species were positively
      influenced by mean patch size, and negatively so by patch isolation. Matrix
      effects were weak, although there was a tendency for a higher proportion of
      occupied patches in more intensive, irrigated agricultural landscapes,
      particularly during the dry season. In terms of conservation, results suggest
      that water voles may be able to cope well with, or even be favoured by, the on
      going expansion of irrigated agriculture in Mediterranean dry-lands, provided
      that a number of patches of wet herbaceous vegetation are maintained within the
      farmland mosaic. Overall, our study suggests that the mosaic-level approach may
      provide a useful framework to understand the responses of patchy populations to
      land use change. 

PMID- 23875015
TI  - A review of the evidence to support influenza vaccine introduction in countries
      and areas of WHO's Western Pacific Region.
AB  - BACKGROUND: Immunization against influenza is considered an essential public
      health intervention to control both seasonal epidemics and pandemic influenza.
      According to the World Health Organization (WHO), there are five key policy and
      three key programmatic issues that decision-makers should consider before
      introducing a vaccine. These are (a) public health priority, (b) disease burden,
      (c) efficacy, quality and safety of the vaccine, (d) other inventions, (e)
      economic and financial issues, (f) vaccine presentation, (g) supply availability
      and (h) programmatic strength. We analyzed the body of evidence currently
      available on these eight issues in the WHO Western Pacific Region.
      METHODOLOGY/PRINCIPAL FINDINGS: Studies indexed in PubMed and published in
      English between 1 January 2000 and 31 December 2010 from the 37 countries and
      areas of the Western Pacific Region were screened for keywords pertaining to the
      five policy and three programmatic issues. Studies were grouped according to
      country income level and vaccine target group. There were 133 articles that met
      the selection criteria, with most (90%) coming from high-income countries.
      Disease burden (n = 34), vaccine efficacy, quality and safety (n = 27) and public
      health priority (n = 27) were most frequently addressed by studies conducted in
      the Region. Many studies assessed influenza vaccine policy and programmatic
      issues in the general population (42%), in the elderly (24%) and in children
      (17%). Few studies (2%) addressed the eight issues relating to pregnant women.
      CONCLUSIONS/SIGNIFICANCE: The evidence for vaccine introduction in countries and
      areas in this Region remains limited, particularly in low- and middle-income
      countries that do not currently have influenza vaccination programmes.
      Surveillance activities and specialized studies can be used to assess the eight
      issues including disease burden among vaccine target groups and the cost
      effectiveness of influenza vaccine. Multi-country studies should be considered to
      maximize resource utilization for cross-cutting issues such as vaccine
      presentation and other inventions.

PMID- 23875016
TI  - Genes dysregulated to different extent or oppositely in estrogen receptor
      positive and estrogen receptor-negative breast cancers.
AB  - BACKGROUND: Directly comparing gene expression profiles of estrogen receptor
      positive (ER+) and estrogen receptor-negative (ER-) breast cancers cannot
      determine whether differentially expressed genes between these two subtypes
      result from dysregulated expression in ER+ cancer or ER- cancer versus normal
      controls, and thus would miss critical information for elucidating the
      transcriptomic difference between the two subtypes. PRINCIPAL FINDINGS: Using
      microarray datasets from TCGA, we classified the genes dysregulated in both ER+
      and ER- cancers versus normal controls into two classes: (i) genes dysregulated
      in the same direction but to a different extent, and (ii) genes dysregulated to
      opposite directions, and then validated the two classes in RNA-sequencing
      datasets of independent cohorts. We showed that the genes dysregulated to a
      larger extent in ER+ cancers than in ER- cancers enriched in glycerophospholipid
      and polysaccharide metabolic processes, while the genes dysregulated to a larger
      extent in ER- cancers than in ER+ cancers enriched in cell proliferation.
      Phosphorylase kinase and enzymes of glycosylphosphatidylinositol (GPI) anchor
      biosynthesis were upregulated to a larger extent in ER+ cancers than in ER-
      cancers, whereas glycogen synthase and phospholipase A2 were downregulated to a
      larger extent in ER+ cancers than in ER- cancers. We also found that the genes
      oppositely dysregulated in the two subtypes significantly enriched with known
      cancer genes and tended to closely collaborate with the cancer genes.
      Furthermore, we showed the possibility that these oppositely dysregulated genes
      could contribute to carcinogenesis of ER+ and ER- cancers through rewiring
      different subpathways. CONCLUSIONS: GPI-anchor biosynthesis and glycogenolysis
      were elevated and hydrolysis of phospholipids was depleted to a larger extent in
      ER+ cancers than in ER- cancers. Our findings indicate that the genes oppositely
      dysregulated in the two subtypes are potential cancer genes which could
      contribute to carcinogenesis of both ER+ and ER- cancers through rewiring
      different subpathways.

PMID- 23875017
TI  - Predictors of costs in dementia in a longitudinal perspective.
AB  - OBJECTIVE: To analyse predictors of costs in dementia from a societal perspective
      in a longitudinal setting. METHOD: Healthcare resource use and costs were
      assessed retrospectively using a questionnaire in four waves at 6-month intervals
      in a sample of dementia patients (N = 175). Sociodemographic data, dementia
      severity and comorbidity at baseline, cognitive impairment and impairment in
      basic and instrumental activities of daily living were also recorded. Linear
      mixed regression models with random intercepts for individuals were used to
      analyse predictors of total and sector-specific costs. RESULTS: Impairment in
      activities of daily living significantly predicted total costs in dementia
      patients, with associations between basic activities of daily living and formal
      care costs on the one and instrumental activities of daily living and informal
      care costs on the other hand. Nursing home residence was associated with lower
      total costs than residence in the community. There was no effect of cognition on
      total or sector-specific costs. CONCLUSION: Cognitive deficits in dementia are
      associated with costs only via their effect on the patients' capacity for
      activities of daily living. Transition into a nursing home may reduce total costs
      from a societal perspective, owing to the fact that a high amount of informal
      care required by severely demented patients prior to transition into a nursing
      home may cause higher costs than inpatient nursing care.

PMID- 23875018
TI  - Immunomodulator clarithromycin enhances mucosal and systemic immune responses and
      reduces re-infection rate in pediatric patients with influenza treated with
      antiviral neuraminidase inhibitors: a retrospective analysis.
AB  - BACKGROUND/AIMS: Treatment with antiviral neuraminidase inhibitors suppresses
      influenza viral replication and antigen production, resulting in marked
      attenuation of mucosal immunity and mild suppression of systemic immunity in
      mice. This study investigated the effects of immunomodulator clarithromycin (CAM)
      supplementation on mucosal and systemic immunity in pediatric patients with
      influenza treated with neuraminidase inhibitors. METHODS: A retrospective, non
      randomized case series study was conducted among five treatment groups of 195
      children aged 5.9+/-3.3 years infected with influenza A in 2008/2009 season. The
      five treatment groups were oseltamivir (OSV), zanamivir (ZNV), OSV+CAM, ZNV+CAM
      and untreated groups. Anti-viral secretory IgA (S-IgA) levels in nasal washes and
      IgG levels in sera were measured. The re-infection rate was analyzed among the
      same five treatment groups in the 2009/2010 season. RESULTS: Treatment of
      influenza with OSV and ZNV for 5 days attenuated the induction of anti-viral S
      IgA in nasal washes and anti-viral IgG in serum, compared with the untreated
      group. The combination of CAM plus OSV or ZNV boosted and restored the production
      of mucosal S-IgA and systemic IgG. The re-infection rates in the subsequent
      season were significantly higher in the OSV and ZNV groups than the untreated,
      while CAM+OSV and CAM+ZNV tended to reduce such rate. CONCLUSIONS: CAM restored
      the attenuated anti-viral mucosal and systemic immunity and reduced the re
      infection rate in the subsequent year in pediatric patients with influenza
      treated with OSV and ZNV.

PMID- 23875019
TI  - Characterization and expression analysis of a fiber differentially expressed
      Fasciclin-like arabinogalactan protein gene in Sea Island cotton fibers.
AB  - Fasciclin-like arabinogalactan (FLA) protein is a cell-wall-associated protein
      playing crucial roles in regulating plant growth and development, and it was
      characterized in different plants including Upland cotton (Gossypium hirsutum
      L.). In cDNA-AFLP analysis of 25 DPA (days post anthesis) fiber mRNA, two FLA
      gene-related transcripts exhibit differential expression between Sea Island
      cotton (G. barbadense L.) and Upland cotton. Based on the transcript-derived
      fragment, RACE-PCR and realtime PCR technique, GbFLA5 full-length cDNA was
      isolated and its expression profiles were characterized in both cotton plant
      tissues and secondary cell wall (SCW) fibers in this study. The 1154 bp GbFLA5
      cDNA contains an ORF of 720 bp, encoding GbFLA5 protein of 239 amino acids
      residues in length with an estimated molecular mass of 25.41 kDa and isoelectric
      point of 8.63. The deduced GbFLA5 protein contains an N-terminal signal sequence,
      two AGP-like domains, a single fasciclin-like domain, and a GPI anchor signal
      sequence. Phylogenetic analysis shows that GbFLA5 protein is homologous to some
      known SCW-specific expressed FLAs of plant developing xylem, tension wood and
      cotton fibers. In the SCW deposition stage from 15 to 45 DPA detected, FLA5
      maintains a significantly higher expression level in Sea Island cotton fibers
      than in Upland cotton fibers. The increasing FLA5 transcript abundance coincided
      with the SCW deposition process and the expression intensity differences
      coincided with their fiber strength differences between Sea Island cotton and
      Upland cotton. These expression profile features of GbFLA5 in cotton fibers
      revealed its tissue-specific and SCW developmental stage-specific expression
      characters. Further analysis suggested that GbFLA5 is a crucial SCW-specific
      protein which may contribute to fiber strength by affecting cellulose synthesis
      and microfibril deposition orientation. 

PMID- 23875020
TI  - A dual-mode surface display system for the maturation and production of
      monoclonal antibodies in glyco-engineered Pichia pastoris.
AB  - State-of-the-art monoclonal antibody (mAb) discovery methods that utilize surface
      display techniques in prokaryotic and eukaryotic cells require multiple steps of
      reformatting and switching of hosts to transition from display to expression.
      This results in a separation between antibody affinity maturation and full-length
      mAb production platforms. Here, we report for the first time, a method in Glyco
      engineered Pichiapastoris that enables simultaneous surface display and secretion
      of full-length mAb molecules with human-like N-glycans using the same yeast cell.
      This paradigm takes advantage of homo-dimerization of the Fc portion of an IgG
      molecule to a surface-anchored "bait" Fc, which results in targeting functional
      "half" IgGs to the cell wall of Pichiapastoris without interfering with the
      secretion of full length mAb. We show the utility of this method in isolating
      high affinity, well-expressed anti-PCSK9 leads from a designed library that was
      created by mating yeasts containing either light chain or heavy chain IgG
      libraries. Coupled with Glyco-engineered Pichiapastoris, this method provides a
      powerful tool for the discovery and production of therapeutic human mAbs in the
      same host thus improving drug developability and potentially shortening the
      discovery time cycle. 

PMID- 23875021
TI  - Pelvic morphology, body posture and standing balance characteristics of
      adolescent able-bodied and idiopathic scoliosis girls.
AB  - The purpose of this study was to determine how pelvic morphology, body posture,
      and standing balance variables of scoliotic girls differ from those of able
      bodied girls, and to classify neuro-biomechanical variables in terms of a lower
      number of unobserved variables. Twenty-eight scoliotic and twenty-five non
      scoliotic able-bodied girls participated in this study. 3D coordinates of ten
      anatomic body landmarks were used to describe pelvic morphology and trunk posture
      using a Flock of Birds system. Standing balance was measured using a force plate
      to identify the center of pressure (COP), and its anteroposterior (AP) and
      mediolateral (ML) displacements. A multivariate analysis of variance (MANOVA) was
      performed to determine differences between the two groups. A factor analysis was
      used to identify factors that best describe both groups. Statistical differences
      were identified between the groups for each of the parameter types. While spatial
      orientation of the pelvis was similar in both groups, five of the eight trunk
      postural variables of the scoliotic group were significantly different that the
      able-bodied group. Also, five out of the seven standing balance variables were
      higher in the scoliotic girls. Approximately 60% of the variation is supported by
      4 factors that can be associated with a set of variables; standing balance
      variables (factor 1), body posture variables (factor 2), and pelvic morphology
      variables (factors 3 and 4). Pelvic distortion, body posture asymmetry, and
      standing imbalance are more pronounced in scoliotic girls, when compared to able
      bodied girls. These findings may be beneficial when addressing balance and ankle
      proprioception exercises for the scoliotic population. 

PMID- 23875022
TI  - Effects of added organic matter and water on soil carbon sequestration in an arid
      region.
AB  - It is generally predicted that global warming will stimulate primary production
      and lead to more carbon (C) inputs to soil. However, many studies have found that
      soil C does not necessarily increase with increased plant litter input.
      Precipitation has increased in arid central Asia, and is predicted to increase
      more, so we tested the effects of adding fresh organic matter (FOM) and water on
      soil C sequestration in an arid region in northwest China. The results suggested
      that added FOM quickly decomposed and had minor effects on the soil organic
      carbon (SOC) pool to a depth of 30 cm. Both FOM and water addition had
      significant effects on the soil microbial biomass. The soil microbial biomass
      increased with added FOM, reached a maximum, and then declined as the FOM
      decomposed. The FOM had a more significant stimulating effect on microbial
      biomass with water addition. Under the soil moisture ranges used in this
      experiment (21.0%-29.7%), FOM input was more important than water addition in the
      soil C mineralization process. We concluded that short-term FOM input into the
      belowground soil and water addition do not affect the SOC pool in shrubland in an
      arid region. 

PMID- 23875023
TI  - IL-10 conditioning of human skin affects the distribution of migratory dendritic
      cell subsets and functional T cell differentiation.
AB  - In cancer patients pervasive systemic suppression of Dendritic Cell (DC)
      differentiation and maturation can hinder vaccination efficacy. In this study we
      have extensively characterized migratory DC subsets from human skin and studied
      how their migration and T cell-stimulatory abilities were affected by
      conditioning of the dermal microenvironment through cancer-related suppressive
      cytokines. To assess effects in the context of a complex tissue structure, we
      made use of a near-physiological skin explant model. By 4-color flow cytometry,
      we identified migrated Langerhans Cells (LC) and five dermis-derived DC
      populations in differential states of maturation. From a panel of known tumor
      associated suppressive cytokines, IL-10 showed a unique ability to induce
      predominant migration of an immature CD14(+)CD141(+)DC-SIGN(+) DC subset with low
      levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory
      molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly
      immature subset composition was observed for DC migrating from explants taken
      from skin overlying breast tumors. Whereas predominant migration of mature
      CD1a(+) subsets was associated with release of IL-12p70, efficient Th cell
      expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+)
      T cells, migration of immature CD14(+) DDC was accompanied by increased release
      of IL-10, poor expansion of CD4(+) and CD8(+) T cells, and skewing of Th
      responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell
      differentiation and outgrowth. Thus, high levels of IL-10 impact the composition
      of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC
      with functional qualities conducive to T cell tolerance. 

PMID- 23875024
TI  - Antiviral responses by Swine primary bronchoepithelial cells are limited compared
      to human bronchoepithelial cells following influenza virus infection.
AB  - Swine generate reassortant influenza viruses because they can be simultaneously
      infected with avian and human influenza; however, the features that restrict
      influenza reassortment in swine and human hosts are not fully understood. Type I
      and III interferons (IFNs) act as the first line of defense against influenza
      virus infection of respiratory epithelium. To determine if human and swine have
      different capacities to mount an antiviral response the expression of IFN and IFN
      stimulated genes (ISG) in normal human bronchial epithelial (NHBE) cells and
      normal swine bronchial epithelial (NSBE) cells was evaluated following infection
      with human (H3N2), swine (H1N1), and avian (H5N3, H5N2, H5N1) influenza A
      viruses. Expression of IFNlambda and ISGs were substantially higher in NHBE cells
      compared to NSBE cells following H5 avian influenza virus infection compared to
      human or swine influenza virus infection. This effect was associated with reduced
      H5 avian influenza virus replication in human cells at late times post infection.
      Further, RIG-I expression was lower in NSBE cells compared to NHBE cells
      suggesting reduced virus sensing. Together, these studies identify key
      differences in the antiviral response between human and swine respiratory
      epithelium alluding to differences that may govern influenza reassortment. 

PMID- 23875025
TI  - The cationic cytokine IL-26 differentially modulates virus infection in culture.
AB  - Interleukin-26 (IL-26) belongs to the IL-10 cytokine family, is produced by
      activated T cells, and targets epithelial target cells for signal transduction.
      Here, we describe the IL-26 effects on the infection of culture cells with
      recombinant vesicular stomatitis virus (VSV), human cytomegalovirus (HCMV), and
      herpes simplex virus type 1 (HSV-1) expressing green fluorescent protein. After
      pre-incubation with recombinant IL-26 and at low multiplicity of infection, VSV
      showed strongly enhanced infection and replication rates as measured for
      infectivity, for transcript levels, and for protein expression. Control proteins
      did not affect VSV infection. The IL-26 effect was independent of the IL-26
      receptor and neutralized by anti-IL-26 serum. Pre-incubation of VSV was much more
      efficient than pre-incubation of the target cells to enhance virus infection. IL
      26 increased virus adsorption to target cells as shown by quantitative reverse
      transcription PCR. In contrast, the infection of IL-26-treated human fibroblasts
      with HCMV was inhibited and the infection by HSV-1 was not altered by IL-26.
      Thus, IL-26 differentially modulates the infection by different enveloped
      viruses. 

PMID- 23875026
TI  - Peroxynitrite is a key mediator of the cardioprotection afforded by ischemic
      postconditioning in vivo.
AB  - Myocardial ischemic postconditioning (PosC) describes an acquired resistance to
      lethal ischemia-reperfusion (I/R) injury afforded by brief episodes of I/R
      applied immediately after the ischemic insult. Cardioprotection is conveyed by
      parallel signaling pathways converging to prevent mitochondria permeability
      transition. Recent observations indicated that PostC is associated with free
      radicals generation, including nitric oxide (NO(.)) and superoxide (O2 (.-)), and
      that cardioprotection is abrogated by antioxidants. Since NO. And O2 (. -) react
      to form peroxynitrite, we hypothesized that postC might trigger the formation of
      peroxyntrite to promote cardioprotection in vivo. Rats were exposed to 45 min of
      myocardial ischemia followed by 3h reperfusion. PostC (3 cycles of 30 seconds
      ischemia/30 seconds reperfusion) was applied at the end of index ischemia. In a
      subgroup of rats, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4
      sulphonatophenyl) porphyrinato iron (FeTPPS) was given intravenously (10 mg/kg(
      1)) 5 minutes before PostC. Myocardial nitrotyrosine was determined as an index
      of peroxynitrite formation. Infarct size (colorimetric technique and plasma
      creatine kinase-CK-levels) and left ventricle (LV) function (micro-tip pressure
      transducer), were determined. A significant generation of 3-nitrotyrosine was
      detected just after the PostC manoeuvre. PostC resulted in a marked reduction of
      infarct size, CK release and LV systolic dysfunction. Treatment with FeTPPS
      before PostC abrogated the beneficial effects of PostC on myocardial infarct size
      and LV function. Thus, peroxynitrite formed in the myocardium during PostC
      induces cardioprotective mechanisms improving both structural and functional
      integrity of the left ventricle exposed to ischemia and reperfusion in vivo. 

PMID- 23875027
TI  - FlyNap (triethylamine) increases the heart rate of mosquitoes and eliminates the
      cardioacceleratory effect of the neuropeptide CCAP.
AB  - FlyNap (triethylamine) is commonly used to anesthetize Drosophila melanogaster
      fruit flies. The purpose of this study was to determine whether triethylamine is
      a suitable anesthetic agent for research into circulatory physiology and immune
      competence in the mosquito, Anopheles gambiae (Diptera: Culicidae). Recovery
      experiments showed that mosquitoes awaken from traditional cold anesthesia in
      less than 7 minutes, but that recovery from FlyNap anesthesia does not begin for
      several hours. Relative to cold anesthesia, moderate exposures to FlyNap induce
      an increase in the heart rate, a decrease in the percentage of the time the heart
      contracts in the anterograde direction, and a decrease in the frequency of
      heartbeat directional reversals. Experiments employing various combinations of
      cold and FlyNap anesthesia then showed that cold exposure does not affect basal
      heart physiology, and that the differences seen between the cold and the FlyNap
      groups are due to a FlyNap-induced alteration of heart physiology. Furthermore,
      exposure to FlyNap eliminated the cardioacceleratory effect of crustacean
      cardioactive peptide (CCAP), and reduced a mosquito's ability to survive a
      bacterial infection. Together, these data show that FlyNap is not a suitable
      substitute to cold anesthesia in experiments assessing mosquito heart function or
      immune competence. Moreover, these data also illustrate the intricate biology of
      the insect heart. Specifically, they confirm that the neurohormone CCAP modulates
      heart rhythms and that it serves as an anterograde pacemaker. 

PMID- 23875028
TI  - Integrated fossil and molecular data reveal the biogeographic diversification of
      the eastern Asian-eastern North American disjunct hickory genus (Carya Nutt.).
AB  - The hickory genus (Carya) contains ca. 17 species distributed in subtropical and
      tropical regions of eastern Asia and subtropical to temperate regions of eastern
      North America. Previously, the phylogenetic relationships between eastern Asian
      and eastern North American species of Carya were not fully confirmed even with an
      extensive sampling, biogeographic and diversification patterns had thus never
      been investigated in a phylogenetic context. We sampled 17 species of Carya and
      15 species representing all other genera of the Juglandaceae as outgroups, with
      eight nuclear and plastid loci to reconstruct the phylogeny of Carya. The
      phylogenetic positions of seven extinct genera of the Juglandaceae were inferred
      using morphological characters and the molecular phylogeny as a backbone
      constraint. Divergence times within Carya were estimated with relaxed Bayesian
      dating. Biogeographic analyses were performed in DIVA and LAGRANGE.
      Diversification rates were inferred by LASER and APE packages. Our results
      support two major clades within Carya, corresponding to the lineages of eastern
      Asia and eastern North America. The split between the two disjunct clades is
      estimated to be 21.58 (95% HPD 11.07-35.51) Ma. Genus-level DIVA and LAGRANGE
      analyses incorporating both extant and extinct genera of the Juglandaceae
      suggested that Carya originated in North America, and migrated to Eurasia during
      the early Tertiary via the North Atlantic land bridge. Fragmentation of the
      distribution caused by global cooling in the late Tertiary resulted in the
      current disjunction. The diversification rate of hickories in eastern North
      America appeared to be higher than that in eastern Asia, which is ascribed to
      greater ecological opportunities, key morphological innovations, and polyploidy. 

PMID- 23875029
TI  - What are lay theories of social class?
AB  - Numerous studies have documented the effects of social class on psychological and
      behavioral variables. However, lay beliefs about how social class affects these
      dimensions have not been systematically tested. Studies 1 and 2 assessed lay
      beliefs about the association between social class and 8 variables (including
      psychological and behavioral tendencies and cognitive ability). Study 3 assessed
      lay beliefs about the Big five personality traits and social class, and study 4
      reframed the 8 variables from study 1 in opposite terms and yielded similar
      results. Study 5 contained the variables framed as in both studies 1 and 4, and
      replicated those results suggesting that framing effects were not responsible for
      the effects observed. Interestingly, for the most part lay beliefs about social
      class did not differ as a function of participants' own social class. In general
      people held relatively accurate and consistent stereotypes about the relationship
      between social class and well-being, health, intelligence, and neuroticism. In
      contrast lay beliefs regarding social class and reasoning styles, as well as
      relational, social, and emotional tendencies were less consistent and coherent.
      This work suggests that on the whole people's beliefs about social class are not
      particularly accurate, and further that in some domains there are contradictory
      stereotypes about the consequences of social class. 

PMID- 23875030
TI  - Has the NTD community neglected evidence-based policy?

PMID- 23875031
TI  - Dissecting the active site of the collagenolytic cathepsin L3 protease of the
      invasive stage of Fasciola hepatica.
AB  - BACKGROUND: A family of secreted cathepsin L proteases with differential
      activities is essential for host colonization and survival in the parasitic
      flatworm Fasciola hepatica. While the blood feeding adult secretes predominantly
      FheCL1, an enzyme with a strong preference for Leu at the S2 pocket of the active
      site, the infective stage produces FheCL3, a unique enzyme with collagenolytic
      activity that favours Pro at P2. METHODOLOGY/PRINCIPAL FINDINGS: Using a novel
      unbiased multiplex substrate profiling and mass spectrometry methodology (MSP
      MS), we compared the preferences of FheCL1 and FheCL3 along the complete active
      site cleft and confirm that while the S2 imposes the greatest influence on
      substrate selectivity, preferences can be indicated on other active site
      subsites. Notably, we discovered that the activity of FheCL1 and FheCL3 enzymes
      is very different, sharing only 50% of the cleavage sites, supporting the idea of
      functional specialization. We generated variants of FheCL1 and FheCL3 with S2 and
      S3 residues by mutagenesis and evaluated their substrate specificity using
      positional scanning synthetic combinatorial libraries (PS-SCL). Besides the rare
      P2 Pro preference, FheCL3 showed a distinctive specificity at the S3 pocket,
      accommodating preferentially the small Gly residue. Both P2 Pro and P3 Gly
      preferences were strongly reduced when Trp67 of FheCL3 was replaced by Leu,
      rendering the enzyme incapable of digesting collagen. In contrast, the inverse
      Leu67Trp substitution in FheCL1 only slightly reduced its Leu preference and
      improved Pro acceptance in P2, but greatly increased accommodation of Gly at S3.
      CONCLUSIONS/SIGNIFICANCE: These data reveal the significance of S2 and S3
      interactions in substrate binding emphasizing the role for residue 67 in
      modulating both sites, providing a plausible explanation for the FheCL3
      collagenolytic activity essential to host invasion. The unique specificity of
      FheCL3 could be exploited in the design of specific inhibitors selectively
      directed to specific infective stage parasite proteinases.

PMID- 23875032
TI  - Mapping the genes for susceptibility and response to Leishmania tropica in mouse.
AB  - BACKGROUND: L. tropica can cause both cutaneous and visceral leishmaniasis in
      humans. Although the L. tropica-induced cutaneous disease has been long known,
      its potential to visceralize in humans was recognized only recently. As nothing
      is known about the genetics of host responses to this infection and their
      clinical impact, we developed an informative animal model. We described
      previously that the recombinant congenic strain CcS-16 carrying 12.5% genes from
      the resistant parental strain STS/A and 87.5% genes from the susceptible strain
      BALB/c is more susceptible to L. tropica than BALB/c. We used these strains to
      map and functionally characterize the gene-loci regulating the immune responses
      and pathology. METHODS: We analyzed genetics of response to L. tropica in
      infected F2 hybrids between BALB/c*CcS-16. CcS-16 strain carries STS-derived
      segments on nine chromosomes. We genotyped these segments in the F2 hybrid mice
      and tested their linkage with pathological changes and systemic immune responses.
      PRINCIPAL FINDINGS: We mapped 8 Ltr (Leishmania tropica response) loci. Four loci
      (Ltr2, Ltr3, Ltr6 and Ltr8) exhibit independent responses to L. tropica, while
      Ltr1, Ltr4, Ltr5 and Ltr7 were detected only in gene-gene interactions with other
      Ltr loci. Ltr3 exhibits the recently discovered phenomenon of transgenerational
      parental effect on parasite numbers in spleen. The most precise mapping (4.07 Mb)
      was achieved for Ltr1 (chr.2), which controls parasite numbers in lymph nodes.
      Five Ltr loci co-localize with loci controlling susceptibility to L. major, three
      are likely L. tropica specific. Individual Ltr loci affect different subsets of
      responses, exhibit organ specific effects and a separate control of parasite load
      and organ pathology. CONCLUSION: We present the first identification of genetic
      loci controlling susceptibility to L. tropica. The different combinations of
      alleles controlling various symptoms of the disease likely co-determine different
      manifestations of disease induced by the same pathogen in individual mice.

PMID- 23875034
TI  - Prospective evaluation of three rapid diagnostic tests for diagnosis of human
      leptospirosis.
AB  - BACKGROUND: Diagnosis of leptospirosis by the microscopic agglutination test
      (MAT) or by culture is confined to specialized laboratories. Although ELISA
      techniques are more common, they still require laboratory facilities. Rapid
      Diagnostic Tests (RDTs) can be used for easy point-of-care diagnosis. This study
      aims to evaluate the diagnostic performance of the RDTs LeptoTek Dri Dot,
      LeptoTek Lateral Flow, and Leptocheck-WB, prospectively. METHODOLOGY: During 2001
      to 2012, one or two of the RDTs at the same time have been applied prior to
      routine diagnostics (MAT, ELISA and culture) on serum specimens from participants
      sent in for leptospirosis diagnosis. The case definition was based on MAT, ELISA
      and culture results. Participants not fulfilling the case definition were
      considered not to have leptospirosis. The diagnostic accuracy was determined
      based on the 1(st) submitted sample and paired samples, either in an overall
      analysis or stratified according to days post onset of illness. RESULTS: The
      overall sensitivity and specificity for the LeptoTek Dri Dot was 75% respectively
      96%, for the LeptoTek Lateral Flow 78% respectively 95%, and for the Leptocheck
      WB 78% respectively 98%. Based on the 1(st) submitted sample the sensitivity was
      low (51% for LeptoTek Dri Dot, 69% for LeptoTek Lateral Flow, and 55% for
      Leptocheck-WB), but substantially increased when the results of paired samples
      were combined, although accompanied by a lower specificity (82% respectively 91%
      for LeptoTek Dri Dot, 86% respectively 84% for LeptoTek Lateral Flow, and 80%
      respectively 93% for Leptocheck-WB). CONCLUSIONS: All three tests present
      antibody tests contributing to the diagnosis of leptospirosis, thus supporting
      clinical suspicion and contributing to awareness. Since the overall sensitivity
      of the tested RDTs did not exceed 80%, one should be cautious to rely only on an
      RDT result, and confirmation by reference tests is strongly recommended.

PMID- 23875033
TI  - Strongyloides stercoralis: Global Distribution and Risk Factors.
AB  - BACKGROUND: The soil-transmitted threadworm, Strongyloides stercoralis, is one of
      the most neglected among the so-called neglected tropical diseases (NTDs). We
      reviewed studies of the last 20 years on S. stercoralis's global prevalence in
      general populations and risk groups. METHODS/PRINCIPAL FINDINGS: A literature
      search was performed in PubMed for articles published between January 1989 and
      October 2011. Articles presenting information on infection prevalence were
      included. A Bayesian meta-analysis was carried out to obtain country-specific
      prevalence estimates and to compare disease odds ratios in different risk groups
      taking into account the sensitivities of the diagnostic methods applied. A total
      of 354 studies from 78 countries were included for the prevalence calculations,
      194 (62.4%) were community-based studies, 121 (34.2%) were hospital-based studies
      and 39 (11.0%) were studies on refugees and immigrants. World maps with country
      data are provided. In numerous African, Asian and South-American resource-poor
      countries, information on S. stercoralis is lacking. The meta-analysis showed an
      association between HIV-infection/alcoholism and S. stercoralis infection (OR:
      2.17 BCI: 1.18-4.01; OR: 6.69; BCI: 1.47-33.8), respectively. CONCLUSIONS: Our
      findings show high infection prevalence rates in the general population in
      selected countries and geographical regions. S. stercoralis infection is
      prominent in several risk groups. Adequate information on the prevalence is still
      lacking from many countries. However, current information underscore that S.
      stercoralis must not be neglected. Further assessments in socio-economic and
      ecological settings are needed and integration into global helminth control is
      warranted.

PMID- 23875035
TI  - Molecular phylodynamic analysis indicates lineage displacement occurred in
      Chinese rabies epidemics between 1949 to 2010.
AB  - Rabies remains a serious problem in China with three epidemics since 1949 and the
      country in the midst of the third epidemic. Significantly, the control of each
      outbreak has been followed by a rapid reemergence of the disease. In 2005, the
      government implemented a rabies national surveillance program that included the
      collection and screening of almost 8,000 samples. In this work, we analyzed a
      Chinese dataset comprising 320 glycoprotein sequences covering 23 provinces and
      eight species, spanning the second and third epidemics. Specifically, we
      investigated whether the three epidemics are associated with a single reemerging
      lineage or a different lineage was responsible for each epidemic. Consistent with
      previous results, phylogenetic analysis identified six lineages, China I to VI.
      Analysis of the geographical composition of these lineages revealed they are
      consistent with human case data and reflect the gradual emergence of China I in
      the third epidemic. Initially, China I was restricted to south China and China II
      was dominant. However, as the epidemic began to spread into new areas, China I
      began to emerge, whereas China II remained confined to south China. By the latter
      part of the surveillance period, almost all isolates were China I and
      contributions from the remaining lineages were minimal. The prevalence of China
      II in the early stages of the third epidemic and its established presence in
      wildlife suggests that it too replaced a previously dominant lineage during the
      second epidemic. This lineage replacement may be a consequence of control
      programs that were dominated by dog culling efforts as the primary control method
      in the first two epidemics. This had the effect of reducing dominant strains to
      levels comparable with other localized background stains. Our results indicate
      the importance of effective control strategies for long term control of the
      disease. 

PMID- 23875037
TI  - Has the NTD community neglected evidence-based policy? PLOS NTDs 2013 expert
      commentary of the viewpoint by Nagpal S, Sinclair D, Garner P.

PMID- 23875036
TI  - Sequential waves of gene expression in patients with clinically defined dengue
      illnesses reveal subtle disease phases and predict disease severity.
AB  - BACKGROUND: Dengue virus (DENV) infection can range in severity from mild dengue
      fever (DF) to severe dengue hemorrhagic fever (DHF) or dengue shock syndrome
      (DSS). Changes in host gene expression, temporally through the progression of
      DENV infection, especially during the early days, remains poorly characterized.
      Early diagnostic markers for DHF are also lacking. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we investigated host gene expression in a cohort of DENV
      infected subjects clinically diagnosed as DF (n = 51) and DHF (n = 13) from
      Maracay, Venezuela. Blood specimens were collected daily from these subjects from
      enrollment to early defervescence and at one convalescent time-point. Using
      convalescent expression levels as baseline, two distinct groups of genes were
      identified: the "early" group, which included genes associated with innate
      immunity, type I interferon, cytokine-mediated signaling, chemotaxis, and
      complement activity peaked at day 0-1 and declined on day 3-4; the second "late"
      group, comprised of genes associated with cell cycle, emerged from day 4 and
      peaked at day 5-6. The up-regulation of innate immune response genes coincided
      with the down-regulation of genes associated with viral replication during day 0
      3. Furthermore, DHF patients had lower expression of genes associated with
      antigen processing and presentation, MHC class II receptor, NK and T cell
      activities, compared to that of DF patients. These results suggested that the
      innate and adaptive immunity during the early days of the disease are vital in
      suppressing DENV replication and in affecting outcome of disease severity. Gene
      signatures of DHF were identified as early as day 1. CONCLUSIONS/SIGNIFICANCE:
      Our study reveals a broad and dynamic picture of host responses in DENV infected
      subjects. Host response to DENV infection can now be understood as two distinct
      phases with unique transcriptional markers. The DHF signatures identified during
      day 1-3 may have applications in developing early molecular diagnostics for DHF.

PMID- 23875038
TI  - Assessment of transmission in trachoma programs over time suggests no short-term
      loss of immunity.
AB  - Trachoma programs have dramatically reduced the prevalence of the ocular
      chlamydia that cause the disease. Some have hypothesized that immunity to the
      infection may be reduced because of program success in reducing the incidence of
      infection, and transmission may then increase. Longitudinal studies of multiple
      communities would be necessary to test this hypothesis. Here, we quantify
      transmission using an estimated basic reproduction number based on 32 communities
      during the first, second, and third years of an antibiotic treatment program. We
      found that there is little to no increase in the basic reproduction number over
      time. The estimated linear trend in the basic reproduction number, [Formula: see
      text], was found to be -0.025 per year, 95% CI -0.167 to 0.117 per year. We are
      unable to find evidence supporting any loss of immunity over the course of a 3
      year program. This is encouraging, as it allows the possibility that repeated
      mass antibiotic distributions may eliminate infection from even the most severely
      affected areas. 

PMID- 23875039
TI  - Achievements and challenges upon the implementation of a program for national
      control of congenital Chagas in Bolivia: results 2004-2009.
AB  - Bolivia is one of the most endemic countries for Chagas disease. Data of 2005
      shows that incidence is around 1.090/00 inhabitants and seroprevalence in
      children under 15 ranged from 10% in urban areas to 40% in rural areas. In this
      article, we report results obtained during the implementation of the congenital
      Chagas program, one of the biggest casuistry in congenital Chagas disease, led by
      National Program of Chagas and Belgian cooperation from 2004 to 2009. The program
      strategy was based on serological results during pregnancy and on the follow up
      of children born from positive mothers until one year old; if positive, treatment
      was done with Benznidazole, 10 mg/Kg/day/30 days with one post treatment control
      6 months later. Throughout the length of the program, a total of 318,479 pregnant
      women were screened and 23.31% were detected positive. 42,538 children born from
      positive mothers were analyzed at birth by micromethod, of which 1.43% read
      positive. 10,120 children returned for their second micromethod control of which
      2.29% read positive, 7,650 children returned for the serological control, of
      which 3.32% turned out positive. From the 1,093 positive children, 70% completed
      the 30 day-treatment and 122 returned for post treatment control with 96% showing
      a negative result. It has been seen that maternal-fetal transmission rates vary
      between 2% and 4%, with an average of 2.6% (about half of previously reported
      studies that reached 5%). In this work, we show that it is possible to implement,
      with limited resources, a National Congenital Chagas Program and to integrate it
      into the Bolivian health system. Keys of success are population awareness, health
      personnel motivation, and political commitment at all levels. 

PMID- 23875040
TI  - Identification of Tsetse (Glossina spp.) using matrix-assisted laser
      desorption/ionisation time of flight mass spectrometry.
AB  - Glossina (G.) spp. (Diptera: Glossinidae), known as tsetse flies, are vectors of
      African trypanosomes that cause sleeping sickness in humans and nagana in
      domestic livestock. Knowledge on tsetse distribution and accurate species
      identification help identify potential vector intervention sites. Morphological
      species identification of tsetse is challenging and sometimes not accurate. The
      matrix-assisted laser desorption/ionisation time of flight mass spectrometry
      (MALDI TOF MS) technique, already standardised for microbial identification,
      could become a standard method for tsetse fly diagnostics. Therefore, a unique
      spectra reference database was created for five lab-reared species of riverine-,
      savannah- and forest- type tsetse flies and incorporated with the commercial
      Biotyper 3.0 database. The standard formic acid/acetonitrile extraction of male
      and female whole insects and their body parts (head, thorax, abdomen, wings and
      legs) was used to obtain the flies' proteins. The computed composite correlation
      index and cluster analysis revealed the suitability of any tsetse body part for a
      rapid taxonomical identification. Phyloproteomic analysis revealed that the peak
      patterns of G. brevipalpis differed greatly from the other tsetse. This outcome
      was comparable to previous theories that they might be considered as a sister
      group to other tsetse spp. Freshly extracted samples were found to be matched at
      the species level. However, sex differentiation proved to be less reliable.
      Similarly processed samples of the common house fly Musca domestica (Diptera:
      Muscidae; strain: Lei) did not yield any match with the tsetse reference
      database. The inclusion of additional strains of morphologically defined wild
      caught flies of known origin and the availability of large-scale mass
      spectrometry data could facilitate rapid tsetse species identification in the
      future. 

PMID- 23875041
TI  - Overexpression of the endothelial protein C receptor is detrimental during
      pneumonia-derived gram-negative sepsis (Melioidosis).
AB  - BACKGROUND: The endothelial protein C receptor (EPCR) enhances anticoagulation by
      accelerating activation of protein C to activated protein C (APC) and mediates
      anti-inflammatory effects by facilitating APC-mediated signaling via protease
      activated receptor-1. We studied the role of EPCR in the host response during
      pneumonia-derived sepsis instigated by Burkholderia (B.) pseudomallei, the
      causative agent of melioidosis, a common form of community-acquired Gram-negative
      (pneumo)sepsis in South-East Asia. METHODOLOGY/PRINCIPAL FINDINGS: Soluble EPCR
      was measured in plasma of patients with septic culture-proven melioidosis and
      healthy controls. Experimental melioidosis was induced by intranasal inoculation
      of B. pseudomallei in wild-type (WT) mice and mice with either EPCR
      overexpression (Tie2-EPCR) or EPCR-deficiency (EPCR(-/-)). Mice were sacrificed
      after 24, 48 or 72 hours. Organs and plasma were harvested to measure colony
      forming units, cellular influxes, cytokine levels and coagulation parameters.
      Plasma EPCR-levels were higher in melioidosis patients than in healthy controls
      and associated with an increased mortality. Tie2-EPCR mice demonstrated enhanced
      bacterial growth and dissemination to distant organs during experimental
      melioidosis, accompanied by increased lung damage, neutrophil influx and cytokine
      production, and attenuated coagulation activation. EPCR(-/-) mice had an
      unremarkable response to B. pseudomallei infection as compared to WT mice, except
      for a difference in coagulation activation in plasma. CONCLUSION/SIGNIFICANCE:
      Increased EPCR-levels correlate with accelerated mortality in patients with
      melioidosis. In mice, transgenic overexpression of EPCR aggravates outcome during
      Gram-negative pneumonia-derived sepsis caused by B. pseudomallei, while
      endogenous EPCR does not impact on the host response. These results add to a
      better understanding of the regulation of coagulation during severe
      (pneumo)sepsis.

PMID- 23875042
TI  - Cathelicidin-like helminth defence molecules (HDMs): absence of cytotoxic, anti
      microbial and anti-protozoan activities imply a specific adaptation to immune
      modulation.
AB  - Host defence peptides (HDPs) are expressed throughout the animal and plant
      kingdoms. They have multifunctional roles in the defence against infectious
      agents of mammals, possessing both bactericidal and immune-modulatory activities.
      We have identified a novel family of molecules secreted by helminth parasites
      (helminth defence molecules; HDMs) that exhibit similar structural and
      biochemical characteristics to the HDPs. Here, we have analyzed the functional
      activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica
      and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian
      HDPs the helminth-derived HDMs show no antimicrobial activity and are non
      cytotoxic to mammalian cells (macrophages and red blood cells). However, both the
      mammalian- and helminth-derived peptides suppress the activation of macrophages
      by microbial stimuli and alter the response of B cells to cytokine stimulation.
      Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved
      to regulate the immune responses of their mammalian hosts by retaining potent
      immune modulatory properties without causing deleterious cytotoxic effects. 

PMID- 23875044
TI  - A single immunization with MVA expressing GnGc glycoproteins promotes epitope
      specific CD8+-T cell activation and protects immune-competent mice against a
      lethal RVFV infection.
AB  - BACKGROUND: Rift Valley fever virus (RVFV) is a mosquito-borne pathogen causing
      an important disease in ruminants often transmitted to humans after epizootic
      outbreaks in African and Arabian countries. To help combat the spread of the
      disease, prophylactic measures need to be developed and/or improved.
      METHODOLOGY/PRINCIPAL FINDINGS: In this work, we evaluated the immunogenicity and
      protective efficacy of recombinant plasmid DNA and modified vaccinia virus Ankara
      (rMVA) vectored vaccines against Rift Valley fever in mice. These recombinant
      vaccines encoded either of two components of the Rift Valley fever virus: the
      viral glycoproteins (Gn/Gc) or the nucleoprotein (N). Following lethal challenge
      with live RVFV, mice immunized with a single dose of the rMVA-Gn/Gc vaccine
      showed no viraemia or clinical manifestation of disease, but mounted RVFV
      neutralizing antibodies and glycoprotein specific CD8+ T-cell responses. Neither
      DNA-Gn/Gc alone nor a heterologous prime-boost immunization schedule (DNA-Gn/Gc
      followed by rMVAGn/Gc) was better than the single rMVA-Gn/Gc immunization
      schedule with regards to protective efficacy. However, the rMVA-Gn/Gc vaccine
      failed to protect IFNAR(-/-) mice upon lethal RVFV challenge suggesting a role
      for innate responses in protection against RVFV. Despite induction of high titer
      antibodies against the RVFV nucleoprotein, the rMVA-N vaccine, whether in
      homologous or heterologous prime-boost schedules with the corresponding
      recombinant DNA vaccine, only conferred partial protection to RVFV challenge.
      CONCLUSIONS/SIGNIFICANCE: Given the excellent safety profile of rMVA based
      vaccines in humans and animals, our data supports further development of rMVA
      Gn/Gc as a vaccine strategy that can be used for the prevention of Rift Valley
      fever in both humans and livestock.

PMID- 23875045
TI  - Health beliefs and practices related to dengue fever: a focus group study.
AB  - BACKGROUND: This qualitative study aimed to provide an in-depth understanding of
      the meaning of dengue fever (DF) amongst people living in a dengue endemic
      region, dengue prevention and treatment-seeking behaviours. The Health Belief
      Model was used as a framework to explore and understand dengue prevention
      behaviours. METHODS: A total of 14 focus group discussions were conducted with 84
      Malaysian citizens of different socio-demographic backgrounds between 16(th)
      December, 2011 and 12(th) May, 2012. RESULTS: The study revealed that awareness
      about DF and prevention measures were high. The pathophysiology of dengue
      especially dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) were
      rarely known; as a result, it was seen as deadly by some but was also perceived
      as easily curable by others without a basis of understanding. Young adults and
      elderly participants had a low perception of susceptibility to DF. In general,
      the low perceived susceptibility emerged as two themes, namely a perceived
      natural ability to withstand infection and a low risk of being in contact with
      the dengue virus vector, Aedes spp. mosquitoes. The barriers to sustained self
      prevention against dengue prevention that emerged in focus groups were: i) lack
      of self-efficacy, ii) lack of perceived benefit, iii) low perceived
      susceptibility, and iv) unsure perceived susceptibility. Low perceived benefit of
      continued dengue prevention practices was a result of lack of concerted action
      against dengue in their neighborhood. Traditional medical practices and home
      remedies were widely perceived and experienced as efficacious in treating DF.
      CONCLUSION: Behavioural change towards attaining sustainability in dengue
      preventive practices may be enhanced by fostering comprehensive knowledge of
      dengue and a change in health beliefs. Wide use of unconventional therapy for DF
      warrants the need to enlighten the public to limit their reliance on unproven
      alternative treatments.

PMID- 23875043
TI  - Population genetics of the filarial worm wuchereria bancrofti in a post-treatment
      region of Papua New Guinea: insights into diversity and life history.
AB  - BACKGROUND: Wuchereria bancrofti (Wb) is the primary causative agent of lymphatic
      filariasis (LF). Our studies of LF in Papua New Guinea (PNG) have shown that it
      is possible to reduce the prevalence of Wb in humans and mosquitoes through mass
      drug administration (MDA; diethylcarbamazine with/without ivermectin). While MDAs
      in the Dreikikir region through 1998 significantly reduced prevalence of Wb
      infection, parasites continue to be transmitted in the area. METHODS: We
      sequenced the Wb mitochondrial Cytochrome Oxidase 1 (CO1) gene from 16 people
      infected with Wb. Patients were selected from 7 villages encompassing both high
      and moderate annual transmission potentials (ATP). We collected genetic data with
      the objectives to (i) document contemporary levels of genetic diversity and (ii)
      distinguish between populations of parasites and hosts across the study area.
      PRINCIPLE FINDINGS: We discovered 109 unique haplotypes currently segregating in
      the Wb parasite population, with one common haplotype present in 15 out of 16
      infections. We found that parasite diversity was similar among people residing
      within the same village and clustered within transmission zones. For example, in
      the high transmission area, diversity tended to be more similar between
      neighboring villages, while in the moderate transmission area, diversity tended
      to be less similar. CONCLUSIONS: In the Dreikikir region of PNG there are
      currently high levels of genetic diversity in populations of Wb. High levels of
      genetic diversity may complicate future MDAs in this region and the presence of
      dominant haplotypes will require adjustments to current elimination strategies.

PMID- 23875046
TI  - Analytical and clinical performance of the CDC real time RT-PCR assay for
      detection and typing of dengue virus.
AB  - Dengue is an acute illness caused by the positive-strand RNA dengue virus (DENV).
      There are four genetically distinct DENVs (DENV-1-4) that cause disease in
      tropical and subtropical countries. Most patients are viremic when they present
      with symptoms; therefore, RT-PCR has been increasingly used in dengue diagnosis.
      The CDC DENV-1-4 RT-PCR Assay has been developed as an in-vitro diagnostic
      platform and was recently approved by the US Food and Drug Administration (FDA)
      for detection of dengue in patients with signs or symptoms of mild or severe
      dengue. The primers and probes of this test have been designed to detect
      currently circulating strains of DENV-1-4 from around the world at comparable
      sensitivity. In a retrospective study with 102 dengue cases confirmed by IgM anti
      DENV seroconversion in the convalescent sample, the RT-PCR Assay detected DENV
      RNA in 98.04% of the paired acute samples. Using sequencing as a positive
      indicator, the RT-PCR Assay had a 97.92% positive agreement in 86 suspected
      dengue patients with a single acute serum sample. After extensive validations,
      the RT-PCR Assay performance was highly reproducible when evaluated across three
      independent testing sites, did not produce false positive results for etiologic
      agents of other febrile illnesses, and was not affected by pathological levels of
      potentially interfering biomolecules. These results indicate that the CDC DENV-1
      4 RT-PCR Assay provides a reliable diagnostic platform capable for confirming
      dengue in suspected cases. 

PMID- 23875047
TI  - Exploring gender dimensions of treatment programmes for neglected tropical
      diseases in Uganda.
AB  - BACKGROUND: Gender remains a recognized but relatively unexamined aspect of the
      potential challenges for treatment programmes for Neglected Tropical Diseases
      (NTDs). We sought to explore the role of gender in access to treatment in the
      Uganda National Neglected Tropical Disease Control Programme.
      METHODOLOGY/PRINCIPAL FINDINGS: Quantitative and qualitative data was collected
      in eight villages in Buyende and Kamuli districts, Eastern Uganda. Quantitative
      data on the number of persons treated by age and gender was identified from
      treatment registers in each village. Qualitative data was collected through semi
      structured interviews with sub-county supervisors, participant observation and
      from focus group discussions with community leaders, community medicine
      distributors (CMDs), men, women who were pregnant or breastfeeding at the time of
      mass-treatment, and adolescent males and females. Findings include the following:
      (i) treatment registers are often incomplete making it difficult to obtain
      accurate estimates of the number of persons treated; (ii) males face more
      barriers to accessing treatment than women due to occupational roles which keep
      them away from households or villages for long periods, and males may be more
      distrustful of treatment; (iii) CMDs may be unaware of which medicines are safe
      for pregnant and breastfeeding women, resulting in women missing beneficial
      treatments. CONCLUSIONS/SIGNIFICANCE: Findings highlight the need to improve
      community-level training in drug distribution which should include gender
      specific issues and guidelines for treating pregnant and breastfeeding women.
      Accurate age and sex disaggregated measures of the number of community members
      who swallow the medicines are also needed to ensure proper monitoring and
      evaluation of treatment programmes.

PMID- 23875048
TI  - Molecular identification of Echinococcus multilocularis infection in small
      mammals from Northeast, Iran.
AB  - BACKGROUND: Alveolar echinococcosis is a zoonotic disease caused by the
      metacestode of Echinococcus multilocularis. Many species of small mammals,
      including arvicolid rodents or Ochotona spp., are natural intermediate hosts of
      the cestode. The main aim of this study was to identify natural intermediate
      hosts of E. multilocularis in Chenaran County, Razavi Khorasan Province,
      northeastern Iran, where the prevalence of infected wild and domestic carnivores
      is high. METHODOLOGY/PRINCIPAL FINDINGS: A program of trapping was carried out in
      five villages in which this cestode was reported in carnivores. The livers of 85
      small mammals were investigated for the presence of E. multilocularis infection
      using multiplex PCR of mitochondrial genes. Infections were identified in 30
      specimens: 23 Microtus transcaspicus, three Ochotona rufescens, two Mus musculus,
      one Crocidura gmelini, and one Apodemus witherbyi. CONCLUSIONS/SIGNIFICANCE: A
      range of small mammals therefore act as natural intermediate hosts for the
      transmission of E. multilocularis in Chenaran County, and the prevalence
      suggested that E. multilocularis infection is endemic in this region. The
      existence of the life cycle of this potentially lethal cestode in the vicinity of
      human habitats provides a significant risk of human infection.

PMID- 23875049
TI  - Hemostatic dysfunction is increased in patients with hepatosplenic
      schistosomiasis mansoni and advanced periportal fibrosis.
AB  - BACKGROUND: Schistosomiasis mansoni is an endemic parasitic disease and a public
      health problem in Northeast Brazil. In some patients, hepatic abnormalities lead
      to periportal fibrosis and result in the most severe clinical form, hepatosplenic
      schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation
      and liver function tests in patients with hepatosplenic schistosomiasis (n = 55)
      correlate with the severity of their periportal fibrosis. METHODOLOGY/PRINCIPAL
      FINDINGS: Blood samples were used for liver function tests, hemogram and
      prothrombin time (International Normalized Ratio, INR). The blood coagulation
      factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa),
      plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry
      or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis
      of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of
      483 ng/mL. Standard liver function tests were all abnormal in the patient group
      compared to healthy controls (n = 29), including raised serum transaminases
      (p<0.001) and lower levels of albumin (p = 0.0156). Platelet counts were 50%
      lower in patients, while for coagulation factors there was a 40% increase in the
      INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared
      to the controls (both p<0.001). Additionally, patients with more advanced
      fibrosis (n = 38) had lower levels of protein C compared to those with only
      central fibrosis (p = 0.0124). The concentration of plasma PAI-1 in patients was
      one-third that of the control group (p<0.001), and D-dimer levels 2.2 times
      higher (p<0.001) with 13 of the 55 patients having levels above the cut-off.
      CONCLUSION/SIGNIFICANCE: This study confirms that hemostatic abnormalities are
      associated with reduced liver function and increased liver fibrosis. Of note was
      the finding that a quarter of patients with hepatosplenic schistosomiasis and
      advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive
      levels of D-dimer, which may predispose them to gastrointestinal bleeding.

PMID- 23875050
TI  - Mycobacterium ulcerans disease: experience with primary oral medical therapy in
      an Australian cohort.
AB  - BACKGROUND: Mycobacterium ulcerans (MU) is responsible for disfiguring skin
      lesions and is endemic on the Bellarine peninsula of southeastern Australia.
      Antibiotics have been shown to be highly effective in sterilizing lesions and
      preventing disease recurrences when used alone or in combination with surgery.
      Our practice has evolved to using primarily oral medical therapy. METHODS: From a
      prospective cohort of MU patients managed at Barwon Health, we describe those
      treated with primary medical therapy defined as treatment of a M. ulcerans lesion
      with antimicrobials either alone or in conjunction with limited surgical
      debridement. RESULTS: From 1/10/2010 through 31/12/11, 43 patients were treated
      with exclusive medical therapy, of which 5 (12%) also underwent limited surgical
      debridement. The median patient age was 50.2 years, and 86% had WHO category 1
      and 91% ulcerative lesions. Rifampicin was combined with ciprofloxacin in 30
      (70%) and clarithromycin in 12 (28%) patients. The median duration of antibiotic
      therapy was 56 days, with 7 (16%) receiving less than 56 days. Medication side
      effects requiring cessation of one or more antibiotics occurred in 7 (16%)
      patients. Forty-two (98%) patients healed without recurrence within 12 months,
      and 1 patient (2%) experienced a relapse 4 months after completion of 8 weeks of
      antimicrobial therapy. CONCLUSION: Our experience demonstrates the efficacy and
      safety of primary oral medical management of MU infection with oral rifampicin
      based regimens. Further research is required to determine the optimal and minimum
      durations of antibiotic therapy, and the most effective antibiotic dosages and
      formulations for young children.

PMID- 23875051
TI  - Ilheus virus isolation in the Pantanal, west-central Brazil.
AB  - The wetlands of the Brazilian Pantanal host large concentrations of diverse
      wildlife species and hematophagous arthropods, conditions that favor the
      circulation of zoonotic arboviruses. A recent study from the Nhecolandia sub
      region of Pantanal reported serological evidence of various flaviviruses,
      including West Nile virus and Ilheus virus (ILHV). According to the age of
      seropositive horses, at least three flaviviruses, including ILHV, circulated in
      the Brazilian Pantanal between 2005 and 2009. To extend this study, we collected
      3,234 adult mosquitoes of 16 species during 2009 and 2010 in the same sub-region.
      Mosquito pool homogenates were assayed for infectious virus on C6/36 and Vero
      cell monolayers and also tested for flaviviral RNA by a group-specific real-time
      RT-PCR. One pool containing 50 non-engorged female specimens of Aedes scapularis
      tested positive for ILHV by culture and for ILHV RNA by real-time RT-PCR,
      indicating a minimum infection rate of 2.5 per 1000. Full-length genomic sequence
      exhibited 95% identity to the only full genome sequence available for ILHV. The
      present data confirm the circulation of ILHV in the Brazilian Pantanal. 

PMID- 23875052
TI  - rKLO8, a novel Leishmania donovani - derived recombinant immunodominant protein
      for sensitive detection of visceral leishmaniasis in Sudan.
AB  - BACKGROUND: For effective control of visceral leishmaniasis (VL) in East Africa,
      new rapid diagnostic tests are required to replace current tests with low
      sensitivity. The aim of this study is to improve diagnosis of VL in East Africa
      by testing a new antigen from an autochthonous L. donovani strain in Sudan.
      METHODOLOGY AND PRINCIPLE FINDINGS: We cloned, expressed and purified a novel
      recombinant protein antigen of L. donovani from Sudan, designated rKLO8, that
      contains putative conserved domains with significant similarity to the
      immunodominant kinesin proteins of Leishmania. rKLO8 exhibited 93% and 88% amino
      acid identity with cloned kinesin proteins of L. infantum (synonymous L. chagasi)
      (K39) and L. donovani (KE16), respectively. We evaluated the diagnostic
      efficiency of the recombinant protein in ELISA for specific detection of VL
      patients from Sudan. Data were compared with a rK39 ELISA and two commercial
      kits, the rK39 strip test and the direct agglutination test (DAT). Of 106
      parasitologically confirmed VL sera, 104 (98.1%) were tested positive by rKLO8 as
      compared to 102 (96.2%) by rK39. Importantly, the patients' sera showed increased
      reactivity with rKLO8 than rK39. Specificity was 96.1% and 94.8% for rKLO8- and
      rK39 ELISAs, respectively. DAT showed 100% specificity and 94.3% sensitivity
      while rK39 strip test performed with 81.1% sensitivity and 98.7% specificity.
      CONCLUSION: The increased reactivity of Sudanese VL sera with the rKLO8 makes
      this antigen a potential candidate for diagnosis of visceral leishmaniasis in
      Sudan. However, the suitability at the field level will depend on its performance
      in a rapid test format.

PMID- 23875053
TI  - Etiology of severe non-malaria febrile illness in Northern Tanzania: a
      prospective cohort study.
AB  - INTRODUCTION: The syndrome of fever is a commonly presenting complaint among
      persons seeking healthcare in low-resource areas, yet the public health community
      has not approached fever in a comprehensive manner. In many areas, malaria is
      over-diagnosed, and patients without malaria have poor outcomes. METHODS AND
      FINDINGS: We prospectively studied a cohort of 870 pediatric and adult febrile
      admissions to two hospitals in northern Tanzania over the period of one year
      using conventional standard diagnostic tests to establish fever etiology. Malaria
      was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in
      only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream
      infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions,
      respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of
      febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24
      (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2
      (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a
      confirmed acute arbovirus infection, all due to chikungunya. No patient had a
      bacterial zoonosis or an arbovirus infection included in the admission
      differential diagnosis. CONCLUSIONS: Malaria was uncommon and over-diagnosed,
      whereas invasive infections were underappreciated. Bacterial zoonoses and
      arbovirus infections were highly prevalent yet overlooked. An integrated approach
      to the syndrome of fever in resource-limited areas is needed to improve patient
      outcomes and to rationally target disease control efforts.

PMID- 23875054
TI  - Targeting the non-structural protein 1 from dengue virus to a dendritic cell
      population confers protective immunity to lethal virus challenge.
AB  - Dengue is the most prevalent arboviral infection, affecting millions of people
      every year. Attempts to control such infection are being made, and the
      development of a vaccine is a World Health Organization priority. Among the
      proteins being tested as vaccine candidates in preclinical settings is the non
      structural protein 1 (NS1). In the present study, we tested the immune responses
      generated by targeting the NS1 protein to two different dendritic cell
      populations. Dendritic cells (DCs) are important antigen presenting cells, and
      targeting proteins to maturing DCs has proved to be an efficient means of
      immunization. Antigen targeting is accomplished by the use of a monoclonal
      antibody (mAb) directed against a DC cell surface receptor fused to the protein
      of interest. We used two mAbs (alphaDEC205 and alphaDCIR2) to target two distinct
      DC populations, expressing either DEC205 or DCIR2 endocytic receptors,
      respectively, in mice. The fusion mAbs were successfully produced, bound to their
      respective receptors, and were used to immunize BALB/c mice in the presence of
      polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation
      stimulus. We observed induction of strong anti-NS1 antibody responses and similar
      antigen binding affinity irrespectively of the DC population targeted.
      Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized
      with alphaDEC-NS1 and alphaDCIR2-NS1 mAbs. When we tested the induction of
      cellular immune responses, the number of IFN-gamma producing cells was higher in
      alphaDEC-NS1 immunized animals. In addition, mice immunized with the alphaDEC-NS1
      mAb were significantly protected from a lethal intracranial challenge with the
      DENV2 NGC strain when compared to mice immunized with alphaDCIR2-NS1 mAb.
      Protection was partially mediated by CD4(+) and CD8(+) T cells as depletion of
      these populations reduced both survival and morbidity signs. We conclude that
      targeting the NS1 protein to the DEC205(+) DC population with poly (I:C) opens
      perspectives for dengue vaccine development. 

PMID- 23875056
TI  - In reply:.

PMID- 23875055
TI  - Occurrence of nontuberculous mycobacterial pulmonary infection in an endemic area
      of tuberculosis.
AB  - The majority of investigations of the epidemiology of nontuberculous mycobacteria
      (NTM) have focused on highly developed nations with a low prevalence of
      tuberculosis. In contrast, the Para state of north Brazil represents an area of
      high tuberculosis prevalence and increasing NTM incidence. Toward the goal of
      understanding the dynamics of infection by all Mycobacterium species, we report
      patient characteristics and the identification of NTM strains isolated from
      sputum samples from patients that were residents of Para, a state in the Amazon
      region, Northern of Brazil, over the period January 2010 through December 2011 (2
      years). The 29 NTM patients comprised 13.5% of positive mycobacterial cultures
      over the 2-year period. A major risk factor for NTM pulmonary disease was
      previous tuberculosis (76%). Further, the average age of NTM patients (52 years)
      was significantly higher than that of tuberculosis patients (39 years) and more
      were female (72.4% vs. 37.4%). Unlike other Brazilian states, NTM pulmonary
      patients in Para were infected with a different spectrum of mycobacteria;
      primarily the rapidly growing Mycobacterium massiliense and Mycobacterium simiae
      complex. 

PMID- 23875057
TI  - Penalized unsupervised learning with outliers.
AB  - We consider the problem of performing unsupervised learning in the presence of
      outliers - that is, observations that do not come from the same distribution as
      the rest of the data. It is known that in this setting, standard approaches for
      unsupervised learning can yield unsatisfactory results. For instance, in the
      presence of severe outliers, K-means clustering will often assign each outlier to
      its own cluster, or alternatively may yield distorted clusters in order to
      accommodate the outliers. In this paper, we take a new approach to extending
      existing unsupervised learning techniques to accommodate outliers. Our approach
      is an extension of a recent proposal for outlier detection in the regression
      setting. We allow each observation to take on an "error" term, and we penalize
      the errors using a group lasso penalty in order to encourage most of the
      observations' errors to exactly equal zero. We show that this approach can be
      used in order to develop extensions of K-means clustering and principal
      components analysis that result in accurate outlier detection, as well as
      improved performance in the presence of outliers. These methods are illustrated
      in a simulation study and on two gene expression data sets, and connections with
      M-estimation are explored.

PMID- 23875058
TI  - Intriguing bronchoalveolar lavage proteome in a case of pulmonary langerhans cell
      histiocytosis.
AB  - BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial
      lung disease associated with tobacco smoke exposure. New insights into its
      pathogenesis and how it differs from that of chronic obstructive pulmonary
      disease (COPD) may be provided by proteomic studies on bronchoalveolar lavage
      fluid (BALF). CASE REPORT: We present the BALF proteome in a biopsy-proven case
      of PLCH and compare it with typical proteomes of COPD and of the healthy lung.
      The BALF proteins were separated by two-dimensional gel electrophoresis (2-DE)
      and the protein patterns were analyzed with a computerized 2-DE imaging system.
      As compared to the healthy subject and the COPD case, the PLCH case showed a
      strikingly different 2-DE pattern. There was much more IgG (heavy chain) and
      orosomucoid, and less alpha1-antitrypsin, surfactant protein-A, haptoglobin,
      cystatin-S, Clara cell protein 10, transthyretin and gelsolin. Moreover, no
      apolipoprotein-A1, pro-apolipoprotein-A1, amyloid P, calgranulin A, or
      calgranulin B was detected at all. CONCLUSIONS: This case of PLCH presents with
      an extreme BALF proteome lacking significant amounts of protective and anti
      inflammatory proteins. Thus, the intriguing BALF proteome opens up new lines of
      research into the pathophysiology of PLCH and how its pathogenesis differs from
      that in COPD.

PMID- 23875059
TI  - Rare presentation of giant cell tumor of bone in the lateral end of the clavicle.
AB  - PATIENT: Male, 30 FINAL DIAGNOSIS: Giant cell bone tumor Symptoms: Bone swelling
      * pain MEDICATION: - Clinical Procedure: - Specialty: Oncology. OBJECTIVE:
      Unusual clinical course. BACKGROUND: Cooper first reported giant cell tumors
      (GCT) in the 18(th) century. The clavicle is a rare site for tumors. Metastatic
      tumors are more common than benign. This is the first case of GCT lateral end of
      clavicle to be reported in the literature. CASE REPORTS: A 30-year-man was
      admitted with a 1-year history of progressively increasing swelling and pain over
      the left lateral end of the clavicle. The plain radiograph and PET scan revealed
      an expansile radiolucent lesion in the lateral end of the clavicle. Swelling was
      epiphsio-metaphyseal in location. It demonstrated geographical type of
      destruction with a narrow zone of transition. There was no periosteal reaction or
      soft-tissue component. The mitotic activity was found to be 0-1/10 HPF. Diagnosis
      was confirmed histopathologically. A wide excision of the mass, including 3 cm of
      healthy tissue of the clavicle, was performed. CONCLUSIONS: The presence of an
      expansile lytic lesion of the lateral end of the clavicle should be taken
      seriously and complete radiological and histopathological investigation should be
      done and giant cell tumor of the bone should be kept in mind despite its rarity.

PMID- 23875060
TI  - Endobronchial metastasis from primary anorectal melanoma.
AB  - PATIENT: Male, 64 FINAL DIAGNOSIS: Metastatic anorectal melanoma with
      endotracheal metastasis Symptoms: Fatigue * weight loss * hematochezia * cough
      MEDICATION: None Clinical Procedure: Biopsy of anal mass * rigid bronchoscopy
      Specialty: Internal medicine * oncology * pulmonology. OBJECTIVE: Rare disease.
      BACKGROUND: Anorectal melanoma is a rare cancer with a poor prognosis. The mean
      survival after diagnosis is 15-25 months. At the time of diagnosis, 61% of
      patients have local regional lymph node metastases, and 21% have distant
      metastases. The lungs are a common site for metastasis for all tumors including
      melanoma. However endobronchial metastasis is a rare phenomenon. Endotracheal
      metastases are even rarer, occurring in only 5% of patients with extrapulmonary
      endobronchial metastases. It is most commonly seen in breast, colorectal, and
      kidney cancers. It is extremely rare for cutaneous melanoma. The mean survival
      after diagnosis is only 15 months and treatment options are limited. CASE REPORT:
      We report the case of a 64 year-old gentleman with newly diagnosed metastatic
      anorectal melanoma. A 3 cm by 3 cm bluish-black, oval-shaped, exophytic mass
      protruding from his anus was found on physical exam. Endobronchial and
      endotracheal metastasis to the trachea were discovered on computed tomography and
      he was subsequently taken to the operating room for argon plasma coagulation
      laser recanalization of his trachea via rigid bronchoscopy, and resection of his
      anal mass. CONCLUSIONS: We have presented the first known case of anorectal
      melanoma with endobronchial metastasis. Palliative APC laser recanalization was
      used to prevent asphyxiation from the endotracheal mass. Endobronchial metastasis
      is uncommon and can be easily mistaken for primary bronchogenic carcinoma. It
      should always be considered when evaluating patients with new lung masses.

PMID- 23875061
TI  - Meta-analysis diagnostic accuracy of SNP-based pathogenicity detection tools: a
      case of UTG1A1 gene mutations.
AB  - Crigler-Najjar syndrome (CNS) type I and type II are usually inherited as
      autosomal recessive conditions that result from mutations in the UGT1A1 gene. The
      main objective of the present review is to summarize results of all available
      evidence on the accuracy of SNP-based pathogenicity detection tools compared to
      published clinical result for the prediction of in nsSNPs that leads to disease
      using prediction performance method. A comprehensive search was performed to find
      all mutations related to CNS. Database searches included dbSNP, SNPdbe, HGMD,
      Swissvar, ensemble, and OMIM. All the mutation related to CNS was extracted. The
      pathogenicity prediction was done using SNP-based pathogenicity detection tools
      include SIFT, PHD-SNP, PolyPhen2, fathmm, Provean, and Mutpred. Overall, 59
      different SNPs related to missense mutations in the UGT1A1 gene, were reviewed.
      Comparing the diagnostic OR, PolyPhen2 and Mutpred have the highest detection
      4.983 (95% CI: 1.24 - 20.02) in both, following by SIFT (diagnostic OR: 3.25, 95%
      CI: 1.07 - 9.83). The highest MCC of SNP-based pathogenicity detection tools, was
      belong to SIFT (34.19%) followed by Provean, PolyPhen2, and Mutpred (29.99%,
      29.89%, and 29.89%, respectively). Hence the highest SNP-based pathogenicity
      detection tools ACC, was fit to SIFT (62.71%) followed by PolyPhen2, and Mutpred
      (61.02%, in both). Our results suggest that some of the well-established SNP
      based pathogenicity detection tools can appropriately reflect the role of a
      disease-associated SNP in both local and global structures. 

PMID- 23875062
TI  - The methylation of the LEPR/LEPROT genotype at the promoter and body regions
      influence concentrations of leptin in girls and BMI at age 18 years if their
      mother smoked during pregnancy.
AB  - To determine whether DNA methylation (DNA-M) of the leptin receptor genotype
      (LEPR/LEPROT) links gestational smoking and leptin serum levels and BMI later in
      life, we focused on female offspring, 18 years of age, from the Isle of Wight
      Birth Cohort (IOWBC). Leptin binds to the leptin receptor encoded by the
      LEPR/LEPROT genotype. Using general linear models, we tested a two-stage model.
      First, we investigated whether single nucleotide polymorphisms (SNPs) acting as
      methylation quantitative trait loci (methQTLs) depending on gestational smoking
      were related to differentially methylated cytosine-phosphate-guanine (CpG) sites.
      In stage 2, we tested whether the selected CpG sites, in interaction with other
      SNPs (modifiable genetic variants, modGV), are associated with serum leptin and
      BMI (stage 2). Children from the IOWBC were followed from birth to age 18.
      Information on gestational smoking was gathered upon delivery. SNPs tagging LEPR
      and LEPROT genes were genotyped. Data on LEPR/LEPROTDNA-M and leptin were
      obtained from blood samples drawn at age 18; to determine BMI, height and weight
      were ascertained. Blood samples were provided by 238 girls. Of the 21 CpG sites,
      interactions between gestational smoking and SNPs were detected for 16 CpGs.
      Methylation of seven of the 16 CpGs were, in interaction with modGVs, associated
      with leptin levels at age 18 years. Two CpGs survived a multiple testing penalty
      and were also associated with BMI. This two-stage model may explain why maternal
      smoking has a long-term effect on leptin levels and BMI in girls at age 18 years.

PMID- 23875063
TI  - Genetic epidemiology of osteoporosis across four microsatellite markers near the
      VDR gene.
AB  - The large amount of positive genetic association data in a number of bone
      diseases suggests functional consequences of Vitamin D receptor (VDR) gene
      polymorphism. In the present study, four microsatellite markers viz., D12S1633,
      D12S1635, D12S347, and D12S96, that lie in the vicinity of the VDR gene on
      chromosome 12 were selected to assess the allele distribution pattern and
      diversity among three groups of individuals - normal, osteopenia and
      osteoporosis. Genetic association study was performed using allele frequency
      data. Total genomic DNA was isolated from the whole blood of 226 individuals,
      after recording their bone mineral density (BMD) using Dual X-ray absorptiometry
      (DXA). All DNA samples were subjected to multiplex Polymerase Chain Reaction
      (PCR) - genotyping. Allele frequencies and genetic diversity parameters like -
      number of alleles, average variance and average heterozygosity across all the
      four markers among three groups were computed. Effect of population
      stratification was excluded by investigating population structure. A trend of
      decreasing genetic diversity across four loci from normal to pre- and post
      disease condition has been observed. Lesser recombination rate (theta) indicates
      linkage between studied microsatellite markers and VDR gene. Statistically
      significant linkage disequilibrium was detected for the allele - 22 of locus
      D12S96 with osteoporosis. A positive association of allele - 22 suggests
      susceptibility to disease whereas predominance of allele - 27 among non -
      diseased group implicates its association with normal bone health. 

PMID- 23875064
TI  - Scrutiny of the CHRNA5-CHRNA3-CHRNB4 smoking behavior locus reveals a novel
      association with alcohol use in a Finnish population based study.
AB  - The CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15q25.1 encoding the
      cholinergic nicotinic receptor subunits is robustly associated with smoking
      behavior and nicotine dependence. Only a few studies to date have examined the
      locus with alcohol related traits and found evidence of association with alcohol
      abuse and dependence. Our main goal was to examine the role of three intensively
      studied single nucleotide polymorphisms, rs16969968, rs578776 and rs588765,
      tagging three distinct loci, in alcohol use. Our sample was drawn from two
      independent Finnish population-based surveys, the National FINRISK Study and the
      Health 2000 (Health Examination) Survey. The combined sample included a total of
      32,592 adult Finns (54% women) of whom 8,356 were assessed for cigarettes per day
      (CPD). Data on alcohol use were available for 31,812 individuals. We detected a
      novel association between rs588765 and alcohol use defined as abstainers and low
      frequency drinkers versus drinkers (OR=1.15, p=0.00007). Additionally, we provide
      precise estimates of strength of the association between the three loci and
      smoking quantity in a very large population based sample. As a conclusion, our
      results provide further evidence for the nicotine-specific role of rs16969968
      (locus 1). Further, our data suggest that the effect of rs588765 (locus 3) may be
      specific to alcohol use as the effect is seen also in never smokers. 

PMID- 23875065
TI  - Maternal blood mitochondrial DNA copy number and placental abruption risk:
      results from a preliminary study.
AB  - Oxidative stress and impaired placental function - pathways implicated in the
      pathogenesis of placental abruption - have their origins extending to
      mitochondrial dysfunction. To the best of our knowledge, there are no published
      reports of associations of placental abruption with circulating mitochondrial DNA
      (mtDNA) copy number - a novel biomarker of systemic mitochondrial dysfunction.
      This pilot case-control study was comprised of 233 placental abruption cases and
      238 non-abruption controls. Real-time quantitative polymerase chain reaction
      (PCR) was used to assess the relative copy number of mtDNA in maternal whole
      blood samples collected at delivery. Logistic regression procedures were used to
      estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). There was
      some evidence of an increased odds of placental abruption with the highest
      quartile of mtDNA copy number (P for trend = 0.09) after controlling for
      confounders. The odds of placental abruption was elevated among women with higher
      mtDNA copy number (>=336.9) as compared with those with lower values (<336.9)
      (adjusted OR = 1.60; 95% CI 1.04-2.46). Women diagnosed with preeclampsia and
      with elevated mtDNA copy number had a dramatically increased odds of placental
      abruption as compared with normotensive women without elevated mtDNA copy number
      (adjusted OR = 6.66; 95% CI 2.58-17.16). Maternal mitochondrial dysfunction
      appears to be associated with placental abruption in the presence of
      preeclampsia. Replication in other studies, particularly prospective cohort
      studies and those that allow for tissue specific assessment of mitochondrial
      dysfunction (e.g., the placenta) are needed to further understand cellular and
      genomic biomarkers of normal and abnormal placental function. 

PMID- 23875068
TI  - Bevacizumab and oral metronomic cyclophosphamide in platinum-resistant ovarian
      cancer.

PMID- 23875066
TI  - Residential smoking restrictions are not associated with reduced child SHS
      exposure in a baseline sample of low-income, urban African Americans.
AB  - Second hand smoke exposure (SHSe) relates to many chronic and acute illnesses.
      Low income African American (AA) maternal smokers and their children have
      disproportionately higher tobacco-use and child SHSe-related morbidity and
      mortality than other populations. While public health officials promote
      residential smoking restrictions to reduce SHSe and promote smoking cessation,
      little is known about the impact of restrictions in changing smoking behavior and
      SHSe in this population. Thus, the purpose of this study was to examine
      associations between residential smoking restrictions, maternal smoking, and
      young children's SHSe in the context of other factors known to influence low
      income AA mothers' smoking behavior. For this study, we used cross-sectional,
      baseline data from 307 AA maternal smokers' pre-treatment interviews completed as
      part of a subsequent behavioral counseling trial to reduce their young (< 4 years
      old) children's SHSe. Residential smoking restriction was dichotomized as 0 = no
      restrictions and 1 = some restrictions. Child urine cotinine provided a biomarker
      of SHSe. Mothers reported cigarettes/day smoked, cigarettes/day exposed to child,
      and intention to quit. Multivariate regressions modeled effects of restriction as
      the primary predictor of smoking and exposure outcomes. Maternal smoking patterns
      such as cigarettes per day (beta = 0.52, p < 0.001) and years smoked (beta = 
      0.11; p = 0.03) along with presence of additional smokers in the home (beta =
      0.10; p = 0.04), but not residential restriction (beta = -0.09, p = 0.10),
      predicted reported SHSe. Restriction did not relate to baby cotinine or maternal
      intention to quit. Thus, residential smoking restrictions may contribute to
      efforts to reduce children's SHSe and promote maternal smoking change; but alone,
      may not constitute a sufficient intervention to protect children. Multi-level
      intervention approaches that include SHSe-reduction residential smoking policies
      plus support and cessation assistance for smokers may be a necessary approach to
      smoke-free home adoption and adherence.

PMID- 23875069
TI  - Updates of the current screening guidelines for the early detection of cervical
      cancer.

PMID- 23875070
TI  - p16(INK4a) immunohistochemistry is a promising biomarker to predict the outcome
      of low grade cervical intraepithelial neoplasia: comparison study with HPV
      genotyping.
AB  - OBJECTIVE: In cervical intraepithelial neoplasia (CIN), p16(INK4a)
      immunohistochemistry has been reported to be a useful diagnostic biomarker.
      However, limited information is available about the association between the
      p16(INK4a) immunohistochemistry and the outcomes of CIN. Here, we report
      p16(INK4a) immunohistochemistry as an effective biomarker to predict the outcomes
      of CIN. METHODS: p16(INK4a) immunohistochemistry was performed in patients with
      CIN from January 2000 to August 2009. Among these patients, we have performed a
      retrospective analysis of the medical records to evaluate the outcome of CIN 1-2
      and performed statistical analysis to determine the correlation between
      p16(INK4a) expression and the outcomes. We also performed HPV genotyping and
      analyzed the relation between the infecting human papillomavirus (HPV) genotype
      and the outcomes. RESULTS: A total of 244 patients, including 82 with CIN 1, 60
      with CIN 2, and 102 with CIN 3, were examined. The rate of p16(INK4a)
      overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for
      CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2
      3 group. In the 131 CIN 1-2 patients, the progression rate was significantly
      higher for the patients showing p16(INK4a) overexpression than for those not
      showing p16(INK4a) overexpression (p=0.005); the regression rate was also found
      to be significantly lower for the patients showing p16(INK4a) overexpression
      (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both
      progression and regression rates were not significantly different between the
      high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381,
      respectively). CONCLUSION: p16(INK4a) overexpression was correlated with the
      outcome of CIN 1-2, and p16(INK4a) is considered to be a superior biomarker for
      predicting the outcome of CIN 1-2 compared with HPV genotyping.

PMID- 23875071
TI  - Multivariate prognostic analysis of adenocarcinoma of the uterine cervix treated
      with radical hysterectomy and systematic lymphadenectomy.
AB  - OBJECTIVE: The aim of this study was to investigate the prognostic factors and
      treatment outcome of patients with adenocarcinoma of the uterine cervix who
      underwent radical hysterectomy with systematic lymphadenectomy. METHODS: A total
      of 130 patients with stage IB to IIB cervical adenocarcinoma treated with
      hysterectomy and systematic lymphadenectomy from 1982 to 2005 were
      retrospectively analyzed. Clinicopathological data including age, stage, tumor
      size, the number of positive node sites, lymphovascular space invasion,
      parametrial invasion, deep stromal invasion (>2/3 thickness), corpus invasion,
      vaginal infiltration, and ovarian metastasis, adjuvant therapy, and survival were
      collected and Cox regression analysis was used to determine independent
      prognostic factors. RESULTS: An estimated five-year survival rate of stage IB1
      was 96.6%, 75.0% in stage IB2, 100% in stage IIA, and 52.8% in stage IIB.
      Prognosis of patients with one positive-node site is similar to that of those
      with negative-node. Prognosis of patients with multiple positive-node sites was
      significantly poorer than that of negative and one positive-node site.
      Multivariate analysis revealed that lymph node metastasis, lymphovascular space
      invasion, and parametrial invasion were independent prognostic factors for
      cervical adenocarcinoma. Survival of patients with cervical adenocarcinoma was
      stratified into three groups by the combination of three independent prognostic
      factors. CONCLUSION: Lymph node metastasis, lymphovascular space invasion, and
      parametrial invasion were shown to be independent prognostic factors for cervical
      adenocarcinoma treated with hysterectomy and systematic lymphadenectomy.

PMID- 23875072
TI  - Prognostic factors and treatment outcome after radiotherapy in cervical cancer
      patients with isolated para-aortic lymph node metastases.
AB  - OBJECTIVE: The purpose of the present study was to evaluate treatment outcomes
      and prognostic factors in cervical cancer patients with isolated para-aortic
      lymph node (PALN) metastases. We especially tried to evaluate PALN factors such
      as size, site and number. METHODS: From August 1994 to December 2009, 40 cervical
      cancer patients with isolated PALN node metastases at initial diagnosis were
      selected for analysis. Patients underwent both extended field external beam and
      intracavitary brachytherapy. Fourteen patients received 5-fluorouracil and
      cisplatin (FP) and 16 patients received weekly concurrent cisplatin. Information
      of PALN, such as size, site, and number, was founded before PALN radiotherapy.
      RESULTS: The median follow-up time after primary treatment was 28.5 months
      (range, 2 to 213 months). The 3-year overall and progression-free survival rate
      after primary treatment was 44.3% and 31.3%, respectively. In multivariate
      analysis including tumor stage, performance status, and chemotherapy, FP regimen
      concurrent chemoradiotherapy was more effective than radiotherapy alone
      (p=0.030). The 3-year progression-free survival rate was 41.9% and 11.1% in
      patients with PALN numbers of <=1 and >=2, respectively (p=0.008). The 3-year
      progression-free survival rate was 42.1% and 19.2% in patients with PALN size of
      <1.5 cm and >=1.5 cm, respectively (p=0.031). CONCLUSION: The radiologic features
      of PALN, such as number or size, can be used to determine prognosis in PALN
      metastatic cervical cancer patients. Furthermore, FP regimen concurrent
      chemoradiotherapy was associated with better patient survival than radiotherapy
      alone. However, more studies are required to confirm possible different treatment
      outcomes between FP and weekly cisplatin regimens.

PMID- 23875074
TI  - Prognostic factors associated with local recurrence in squamous cell carcinoma of
      the vulva.
AB  - OBJECTIVE: To analyze the prognostic factors related to the recurrence rate of
      vulvar cancer. METHODS: Retrospective study of 87 patients diagnosed of vulvar
      squamous cell carcinoma diagnosed at a tertiary hospital in Madrid between
      January 2000 and December 2010. RESULTS: The pathological mean tumor size was
      35.1+/-22.8 mm, with stromal invasion of 7.7+/-6.6 mm. The mean free margin after
      surgery was 16.8+/-10.5 mm. Among all patients, 31 (35.6%) presented local
      recurrence (mean time 10 months; range, 1 to 114 months) and 7 (8%) had distant
      metastases (mean time, 5 months; range, 1 to 114 months). We found significant
      differences in the mean tumor size between patients who presented a relapse and
      those who did not (37.6+/-21.3 mm vs. 28.9+/-12.1 mm; p=0.05). Patients with free
      margins equal or less than 8 mm presented a relapse rate of 52.6% vs. 43.5% of
      those with free margin greater than 8 mm (p=0.50). However, with a cut-off of 15
      mm, we observed a local recurrence rate of 55.6% vs. 34.5%, respectively
      (p=0.09). When the stromal invasion cut-off was >4 mm, local recurrence rate
      increased up to 52.9% compared to 37.5% when the stromal invasion was <=4 mm
      (p=0.20). CONCLUSION: Tumor size, pathologic margin distance and stromal invasion
      seem to be the most important predictors of local vulvar recurrence. We consider
      the cut-off of 35 mm of tumor size, 15 mm tumor-free surgical margin and stromal
      invasion >4 mm, high risk predictors of local recurrence rate.

PMID- 23875073
TI  - Disease progression and recurrence in women treated for vulvovaginal
      intraepithelial neoplasia.
AB  - OBJECTIVE: The malignant potential of intraepithelial neoplasia of the vulva and
      vagina after treatment is not well defined. Our objective was to examine risk
      factors for recurrence and invasive disease. METHODS: Four hundred sixty-four
      women with biopsy proven high-grade intraepithelial neoplasia of the vulva and
      vagina were identified in the electronic databases of four colposcopy clinics.
      Inclusion criteria were a follow-up of more than one year, no history of invasive
      cancer and no invasive cancer within the first year after initial treatment. We
      investigated the potential factors associated with recurrence and progression
      using a logistic regression analysis to estimate odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: Of the 411 eligible patients, 123 patients
      (29.9%) recurred later than one year after initial treatment and 24 patients
      (5.8%) progressed to invasive disease. According to multivariate analyses, the
      risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI,
      2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as
      initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and
      smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to
      invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25),
      multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI,
      1.16 to 7.60), but not treatment modality. CONCLUSION: Laser evaporation combined
      with extensive biopsy is at least as efficacious as initial treatment of
      intraepithelial neoplasia with excision. Smoking is a risk factor for both
      recurrence and progression to invasive disease. Hence, smoking cessation should
      be advised and maintaining a long follow-up period due to late relapses is
      necessary.

PMID- 23875075
TI  - Ovarian cancer mortality among women aged 40-79 years in relation to reproductive
      factors and body mass index: latest evidence from the Japan Collaborative Cohort
      study.
AB  - OBJECTIVE: This study mainly aimed to investigate the association of ovarian
      cancer mortality with reproductive factors and body mass index among Japanese
      women aged 40-79 years. METHODS: The source of the data was the Japan
      Collaborative Cohort (JACC) study which covered the period of 1988 to 2009. A
      representative sample of 64,185 women was used. Cox model was used to estimate
      the relative risk (RR) and 95% confidence interval (CI). RESULTS: The total
      number of ovarian cancer deaths was 98, with a mortality rate of 9.30 per 100,000
      person-years. Women with single marital status revealed significantly higher age
      adjusted RR (RR, 4.11; 95% CI, 1.66 to 10.23; p=0.005) as compared to married
      women. The effect of single marital status was stronger among older women aged
      50+ years (RR, 4.58; 95% CI, 1.65 to 12.72; p=0.003) than younger women. An
      elevated risk was found for both nulliparous and nullipregnant women. Similarly,
      an increased risk of ovarian cancer mortality was estimated among overweight
      among aged 50 years or less. CONCLUSION: Out of many factors only single marital
      status indicated a higher risk for ovarian cancer mortality. All other factors
      provided inconclusive results, which imply further epidemiological
      investigations.

PMID- 23875076
TI  - The combination of intravenous bevacizumab and metronomic oral cyclophosphamide
      is an effective regimen for platinum-resistant recurrent ovarian cancer.
AB  - OBJECTIVE: To determine the efficacy, progression-free survival (PFS) and overall
      survival (OS) for the combination of intravenous bevacizumab and oral
      cyclophosphamide in heavily pretreated patients with recurrent ovarian carcinoma.
      METHODS: A retrospective review was performed for all patients with recurrent
      ovarian carcinoma treated with intravenous bevacizumab 10 mg/kg every 14 days and
      oral cyclophosphamide 50 mg daily between January 2006 and December 2010.
      Response to treatment was determined by Response Evaluation Criteria in Solid
      Tumors criteria and/or CA-125 levels. RESULTS: Sixty-six eligible patients were
      identified. Median age was 53 years. Fifty-five patients (83%) had undergone
      optimal cytoreduction. All patients were primarily or secondarily platinum
      resistant at the time of administration of bevacizumab and cyclophosphamide. The
      median number of prior chemotherapy treatments was 6.5 (range, 3 to 16). Eight
      patients (12.1%) had side effects which required discontinuation of bevacizumab
      and cyclophosphamide. There was one bowel perforation (1.5%). Overall response
      rate was 42.4%, including, complete response in 7 patients (10.6%), and partial
      response in 21 patients (31.8%), while 15 patients (22.7%) had stable disease and
      23 patients (34.8%) had disease progression. Median PFS for responders was 5
      months (range, 2 to 14 months). Median OS from initiation of bevacizumab and
      cyclophosphamide was 20 months (range, 2 to 56 months) for responders and 9
      months (range, 2 to 51 months) for non-responders (p=0.004). CONCLUSION:
      Bevacizumab and cyclophosphamide is an effective, well-tolerated chemotherapy
      regimen in heavily pretreated patients with recurrent ovarian carcinoma. This
      combination significantly improved PFS and OS in responders. Response rates were
      similar and favorable to the rates reported for similar patients receiving other
      commonly used second-line chemotherapeutic agents.

PMID- 23875077
TI  - Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial
      mesenchymal transition.
AB  - OBJECTIVE: Over-expression of thrombin in ovarian cancer cells is associated with
      poor prognosis. In this study, we investigated the role of thrombin in inducing
      epithelial-mesenchymal transition (EMT) in SKOV3 epithelial ovarian cancer cells.
      METHODS: After thrombin treatment SKOV3 cells were subjected to western blots,
      reverse-transcription PCR, and enzyme-linked immunosorbent assay to quantify EMT
      related proteins, mRNA expression of SMAD2, DKK1, and sFRP1, and the secretion of
      matrix metalloproteinases (MMPs) and cytokines. Meanwhile, invasion ability was
      evaluated using transwell assays. RESULTS: The results indicated a dose- and time
      dependent down-regulation of E-cadherin and upregulation of N-cadherin and
      vimentin in thrombin-treated SKOV3 cells, compared with the thrombin-free control
      group (p<0.05). There was a dose- and time-dependent increase in the levels of
      SMAD2 and DKK1 mRNAs and a decrease in the levels of sFRP1 mRNA in thrombin
      treated SKOV3 cells compared to control cells (p<0.05). Thrombin-treated SKOV3
      cells exhibited increased secretion of MMP-9, MMP-2, interleukin (IL)-8, and IL-6
      and increased invasion compared to untreated cells (p<0.05). Thrombin altered the
      morphology of SKOV3 cells to a spindle-like phenotype. Addition of hirudin to
      thrombin-treated cells reversed the effects of thrombin. CONCLUSION: Thrombin
      induced EMT and promoted the invasion of SKOV3 cells, possibly via distinct
      signaling pathways. Hirudin inhibited the effects of thrombin, suggesting that
      anticoagulant therapy could be a novel therapeutic strategy for ovarian
      carcinoma.

PMID- 23875078
TI  - Selective cyclooxygenase inhibitors increase paclitaxel sensitivity in taxane
      resistant ovarian cancer by suppressing P-glycoprotein expression.
AB  - OBJECTIVE: The purpose of this study was to investigate whether selective
      cyclooxygenase (COX) inhibitors promote paclitaxel-induced apoptosis in taxane
      resistant ovarian cancer cells by suppressing MDR1/P-glycoprotein (P-gp)
      expression. METHODS: Taxane-resistant ovarian cancer cells were cultured with
      paclitaxel alone or combined with a selective COX inhibitors. The expression
      patterns of MDR1/P-gp and the ability of COX inhibitors to inhibit growth of
      taxane-resistant ovarian cancer cells were measured. The efficacy of
      prostaglandin E2 (PGE2) supplementation was measured to evaluate the mechanisms
      involved in suppressing MDR1 gene expression. RESULTS: P-gp was upregulated in
      taxane-resistant ovarian cancer cells compared to paired paclitaxel-sensitive
      ovarian cancer cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay showed that selective COX inhibitors significantly enhanced
      the cytotoxic effects of paclitaxel in taxane-resistant ovarian cancer cells via
      a prostaglandin-independent mechanism. These increased apoptotic effects were
      further verified by measuring an increased percentage of cells in sub-G1 stage
      using flow cytometry. Selective COX inhibitors suppressed MDR1 and P-gp
      expression. Moreover, combined treatment with paclitaxel and selective COX
      inhibitors increased poly (ADP-ribose) polymerase (PARP) cleavage in taxane
      resistant ovarian cancer cells. CONCLUSION: Selective COX inhibitors
      significantly promote paclitaxel-induced cell death in taxane-resistant ovarian
      cancer cells in a prostaglandin-independent manner. COX inhibitors could be
      potent therapeutic tools to promote paclitaxel sensitization of taxane-resistant
      ovarian cancers by suppressing MDR1/P-gp, which is responsible for the efflux of
      chemotherapeutic agents.

PMID- 23875079
TI  - The course of fatigue in patients with gynecologic and breast cancer.
AB  - OBJECTIVE: The objective of this study is to examine the course of fatigue in
      female cancer patients during the first months after treatment. METHODS: We
      examined a sample of 110 patients suffering from gynecological or breast cancer.
      Fatigue was assessed with two questionnaires, the Multidimensional Fatigue
      Inventory (MFI) and the fatigue scale of the quality of life questionnaire
      European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30).
      Participants were tested during their stay in the hospital (t1), two weeks after
      discharge (t2), and three months after discharge (t3). RESULTS: Fatigue in the
      patients' sample was markedly higher than the general population reference
      values. At t1, the effect sizes are d=0.81 (MFI) and d=1.21 (EORTC QLQ-C30
      fatigue scale). Age and tumor stage had no significant influence on fatigue, but
      patients with a long time since diagnosis had higher fatigue levels than patients
      with a shorter time since diagnosis. From t1 to t3, fatigue mean scores
      decreased. The correlations between the t1 and the t3 fatigue scores were weak,
      with correlation coefficients of only about 0.30. CONCLUSION: Though the mean
      scores of fatigue, averaged across all patients, decreased over the first three
      months, the individual courses could not be predicted from the t1 score.

PMID- 23875080
TI  - Neoadjuvant chemotherapy followed by fertility-sparing surgery for women with
      stage IB1 cervical cancer.
AB  - Fertility-sparing surgery was optimal to patients with tumor diameter smaller
      than 2 cm. For patients with larger tumors, neoadjuvant chemotherapy can debulk
      the tumor and offer the chance of surgery. We report 2 cases of stage IB1
      cervical cancer treated by neoadjuvant chemotherapy and fertility-sparing
      surgery. Relevant literature was reviewed. Its safety, efficacy, and reproductive
      outcome need to be validated in the future. 

PMID- 23875081
TI  - Knowledge, Attitude, Practice, and Status of Infection Control among Iranian
      Dentists and Dental Students: A Systematic Review.
AB  - BACKGROUND AND AIMS: Infection control is an important issue in dentistry, and
      the dentists are primarily responsible for observing the relevant procedures.
      Therefore, the present study evaluated knowledge, attitude, practice, and status
      of infection control among Iranian dentists through systematic review of
      published results. MATERIALS AND METHODS: In this systematic review, the required
      data was collected searching for keywords including infection, infection control,
      behavior, performance, practice, attitude, knowledge, dent*, prevention, Iran*
      and their Persian equivalents in PubMed, Science Direct, Iranmedex, SID, Medlib,
      and Magiran databases with a time limit of 1985 to 2012. Out of 698 articles, 15
      completely related articles were finally considered and the rest were excluded
      due to lake of relev-ance to the study goals. The required data were extracted
      and summarized in an Extraction Table and were analyzed ma-nually. RESULTS:
      Evaluating the results of studies indicated inappropriate knowledge, attitude,
      and practice regarding infection control among Iranian dentists and dental
      students. Using personal protection devices and observing measures required for
      infection control were not in accordance with global standards. CONCLUSION: The
      knowledge, attitudes, and practice of infection control in Iranian dental
      settings were found to be inadequate. Therefore, dentists should be educated more
      on the subject and special programs should be in place to monitor the dental
      settings for observing infection control standards.

PMID- 23875082
TI  - Effect of Surface Treatment with Er;Cr:YSSG, Nd:YAG, and CO2 Lasers on Repair
      Shear Bond Strength of a Silorane-based Composite Resin.
AB  - Background and aims. The aim of the present study was to compare the effect
      ofsurface treatment with Er; Cr:YSSG, Nd:YAG, and CO2 lasers on repair shear bond
      strength of a silorane-based composite resin. Materials and methods. Sixty eight
      cylindrical samples of a silorane-based composite resin (Filtek Silorane) were
      pre-pared and randomly divided into 4 groups as follows: group 1: without surface
      treatment; groups 2, 3 and 4 with surface treatments using Er; Cr:YSSG, Nd:YAG,
      and CO2 lasers, respectively. A positive control group (group 5) was assigned in
      order to measure cohesive strength. Repair shear bond strength values were
      measured and data was analyzed using one-way ANOVA and a post hoc Tukey test at a
      significance level of alpha=0.05. Results. There were statistically significant
      differences in repair shear bond strength values between group 2 and other groups
      (P < 0.05); and between group 1and groups 3and 4 (P < 0.001); however, there were
      no significant differences be-tween groups 3 and 4 (P = 0.91). Conclusion. The
      repair shear bond strength of silorane-based composite resin was acceptable by
      surface treatment with lasers. 

PMID- 23875083
TI  - Shear Bond Strength of an Etch-and-rinse Adhesive to Er:YAG Laser- and/or
      Phosphoric Acid-treated Dentin.
AB  - Background and aims. Er:YAG laser irradiation has been claimed to improve the
      adhesive properties of dentin; therefore, it has been proposed as an alternative
      to acid etching. The aim of this in vitro study was to investigate the shear bond
      strength of an etch-and-rinse adhesive system to dentin surfaces following Er:YAG
      laser and/or phosphoric acid etching. Materials and methods. The roots of 75
      sound maxillary premolars were sectioned below the CEJ and the crowns were
      embedded in auto-polymerizing acrylic resin with the buccal surfaces facing up.
      The buccal surfaces were ground using a diamond bur and polished until the dentin
      was exposed; the samples were randomly divided into five groups (n=15) according
      to the surface treatment: (1) acid etching; (2) laser etching; (3) laser etching
      followed by acid etching; (4) acid etching followed by laser etching and (5) no
      acid etching and no laser etching (control group). Composite resin rods (Point 4,
      Kerr Co) were bonded to treated dentin surfaces with an etch-and-rise adhesive
      system (Optibond FL, Kerr Co) and light-cured.After storage for two weeks at 37
      degrees C and 100% humidity and then thermocycling, bond strength was measured
      with a Zwick Universal Testing Machine at a crosshead speed of 1 mm/min. Data was
      analyzed using parametric and non-parametric tests (P<0.05). Results. Mean shear
      bond strength for acid etching (20.1+/-1.8 MPa) and acid+laser (15.6+/-3.5 MPa)
      groups were significantly higher than those for laser+acid (15.6+/-3.5 MPa),
      laser etching (14.1+/-3.4 MPa) and control (8.1+/-2.1 MPa) groups. However, there
      were no significant differences between acid etching and acid+laser groups, and
      between laser+acid and laser groups. Conclusion. When the cavity is prepared by
      bur, it is not necessary to etch the dentin surface by Er:YAG laser following
      acid etching and acid etching after laser etching. 

PMID- 23875084
TI  - Comparison of the Effect of Nd:YAG and Diode Lasers and Photodynamic Therapy on
      Microleakage of Class V Composite Resin Restorations.
AB  - BACKGROUND AND AIMS: Considering the importance of disinfecting dentin after
      cavity preparation and the possible effect of disinfection methods on induction
      of various reactions between the tooth structure and the adhesive restorative
      material, the aim of the present study was to evaluate microleakage of composite
      resin restorations after disinfecting the prepared dentin surface with Nd:YAG and
      Diode lasers and photodynamic therapy. MATERIALS AND METHODS: Standard Class V
      cavities were prepared on buccal surfaces of 96 sound bovine teeth. The samples
      were randomly divided into 4 groups based on the disinfection method: Group 1:
      Nd:YAG laser; Group 2: Diode laser; Group 3: photodynamic therapy; and Group 4:
      the control. Self-etch bonding agent (Clearfil SE Bond) was applied and all the
      cavities were restored with composite resin (Z100). After thermocycling and
      immersing in 0.5% basic fuchsin, the samples were prepared for microleakage
      evaluation under a stereomicroscope. Data was analyzed with Kruskal-Wallis and
      Wilcoxon signed-rank tests at P<0.05. RESULTS: There were no significant
      differences in the microleakage of occlusal and gingival margins between the
      study groups (P>0.05). There were no significant differences in microleakage
      between the occlusal and gingival margins in the Nd:YAG laser group (P>0.05). In
      the other groups, microleakage at gingival margins was significantly higher than
      that at the occlusal margins (P<0.05). CONCLUSION: Nd:YAG and Diode lasers and
      photodynamic therapy can be used to disinfect cavity preparations before
      composite resin restorations.

PMID- 23875085
TI  - Effect of MTA and Portland Cement on Fracture Resistance of Dentin.
AB  - Background and aims. It is important to evaluate the effects of endodontic
      materials on tooth structures to avoid endodontic treatment failure. The aim of
      the present study was to investigate the effect of mineral trioxide aggregates
      (MTA) and Portland cement (PC) on fracture resistance of dentin. Materials and
      methods. Thirty-six freshly extracted human single-rooted premolar teeth were
      selected. The crowns were removed and the roots were randomly divided into two
      experimental groups and one control group. The root samples were longitudinally
      divided into two halves and a dentin bar (2*2*10 mm) was cut from each root
      section for short-term (2weeks) and long-term (12 weeks) evaluations. The root
      sections in the experimental groups were exposed to MTA or PC, while keeping the
      control group specimens in physiologic saline. The fracture resistance of each
      specimen was measured using an Instron testing machine. The results were
      statistically analyzed using ANOVA, a post hoc Tukey test and paired t-test at 5%
      significance level. Results. The fracture resistance of MTA-treated specimens
      significantly increased between 2 and 12 weeks (P<0.05). After 12 weeks, MTA
      treated specimens had the highest fracture resistance. In the PC group, the
      fracture resistance of specimens did not change significantly over time (P>0.05).
      Conclusion. The results showed that MTA increased the fracture resistance of root
      dentin, while PC had no significant effect on dentin fracture resistance. 

PMID- 23875086
TI  - Efficacy of Pilocarpine and Bromhexine in Improving Radiotherapy-induced
      Xerostomia.
AB  - Background and aims. Xerostomia is one of the most common complications of head
      and neck radiotherapy. The aim of this study was to evaluate and compare the
      efficacy of pilocarpine and bromhexine in improving radiotherapy-induced
      xerostomia and its associated symptoms. Materials and methods. In this single
      blind, randomized crossover study, pilocarpine and bromhexine tablets were used
      by twenty-five patients suffered from xerostomia, with a medical history of head
      and neck radiotherapy. At step A, the patients were treated with pilocarpine for
      2 weeks. In addition, they were asked to take bromhexine for 2 weeks with a one
      week washout period. At step B, the inverse process was conducted (first
      bromhexine, then pilocarpine). Whole resting saliva was collected from patients
      before and after receiving each medication by precise measurements. Then,
      efficacy of the two drugs in the treatment of xerostomia and its related oral
      complications was evaluated using questionnaires by Dichotomous format. The
      results were statistically analyzed using t-student and Fisher's exact and chi
      squared tests. Statistical significance was set at P<0.05. Results. The
      difference between saliva secretion rates before and after medications was not
      significant for bromhexine users at two steps of the study (P=0.35); however, it
      was significant for pilocarpine users (P=0.0001). Users of both drugs showed
      significant differences in improvement of xerostomia, chewing, swallowing,
      tasting and mouth burning. Conclusion. Pilocarpine is probably more effective in
      improving xerostomia and its associated problems compared with bromhexine,
      although the use of the latter was also shown to ease some of the consequences of
      radiotherapy in the head and neck region. 

PMID- 23875087
TI  - Serum Level of Interleukin 17 in Patients with Erosive and Non erosive Oral
      Lichen Planus.
AB  - BACKGROUND AND AIMS: Oral lichen planus is a relatively common chronic oral
      mucosal disease of unknown etiology. Regarding numerous studies on the
      immunologic factors involved in the etiology of lichen planus, the present study
      evaluated the serum interleukin-17 (IL-17) level in patients with erosive and non
      erosive oral lichen planus. MATERIALS AND METHODS: This descriptive analytical
      study included 24 patients with erosive oral lichen planus (EOLP), 24 patients
      with non-erosive oral lichen planus (NEOLP) and 24 healthy volunteered as
      control. Blood samples of the subjects underwent ELISA, using special kits, to
      determine serum interleukin-17 levels. Data was analyzed using with descriptive
      statistic, chi-square test, and one-way ANOVA and Tukey post-hoc test with SPSS
      16 software. RESULTS: EOLP patients showed a high level of serum IL-17 compared
      with NEOLP patents and control groups (EOLP=184.16 +/- 12.41 pg/mL,
      NEOLP=106.09+/-10.78 pg/mL, control=15.50 +/- 4.34 pg/mL, P - 0.001). CONCLUSION:
      High level of serum IL-17 in erosive oral lichen planus patients compared to the
      non-erosive type and healthy individuals may be the reason for higher
      inflammation and atrophy in the erosive type.

PMID- 23875088
TI  - Efficacy of Subgingival Application of Xanthan-based Chlorhexidine Gel Adjunctive
      to Full-mouth Root Planing Assessed by Real-time PCR: A Microbiologic and
      Clinical Study.
AB  - BACKGROUND AND AIMS: The aim of this clinical investigation was to compare
      clinical and microbiological effectiveness of adjunctive CHX gel in the treatment
      of periodontitis. MATERIALS AND METHODS: Twenty-four subjects with localized or
      generalized moderate-to-severe chronic periodontitis underwent scaling and root
      planing. One tooth in each quadrant with a probing depth of >4 mm was chosen for
      combined gel and SRP, with contralateral tooth as control (SRP treated site).
      Clinical assessment was carried out at baseline and 1 and 3 months later;
      microbial assessment was performed by real-time PCR. Periodontal probing depth
      (PPD) was considered as primary outcome. RESULTS: Twenty patients completed the
      study. Baseline PPDs were 4.90+/-0.78 and 5.05+/-0.79 in the SRP and gel groups,
      respectively (P>0.05), which decreased to 3.67+/-0.59 and 3.7+/-0.83 one month
      after treatment and 3.25+/-0.65 and 3.38+/-0.79 three months after treatment.
      Although values decreased significantly in both groups after one and three months
      (P=0.001 in the SRP and P=0.001 in the gel group), the inter-group difference was
      not significant neither at one-month (P=0.47) nor at three-month (P=0.77)
      intervals. The only clinical parameters exhibiting statistically significant
      inter-group differences was BOP in both one-month (P=0.004) and three-month
      (P=0.0001) intervals. All the other clinical measurements showed significant
      decreases after one and three months in both sites but without inter-group
      differences. CONCLUSION: Subgingival application of xanthan chlorhexidine gel
      combined with scaling and root planing reduced bleed-ing of periodontal pockets.
      Clinical trials to evaluate effectiveness of this gel in aggressive and severe
      periodontitis modified by systemic factors are suggested.

PMID- 23875089
TI  - Antibiotic Resistance in Enterococcus faecalis Isolated from Hospitalized
      Patients.
AB  - BACKGROUND AND AIMS: Enterococci are Gram-positive cocci that often occur in
      pairs (diplococci) or short chains. Be-side developing high level of antibiotic
      resistance, these bacteria can cause wide range of disease in human, thus to help
      provide an effective treatment for infections caused by this genus, this study
      was conceived to provide information on Enterococcus faecalis Antibiotic
      resistance to widely used antibiotics in hospitalized patients. MATERIALS AND
      METHODS: Disk diffusion agar and Broth dilution methods were used to perform
      Antibiogram test on isolated Enterococcus faecalis. Culture medium used for Disk
      diffusion agar test was Muller Hinton agar, and for Broth dilution methods,
      Muller Hinton broth culture medium was utilized. In disk diffusion agar method,
      different commercial antibiotics disks produced by Pharmaceutical companies were
      used. Microsoft Excel software was used to perform statistical analysis. RESULTS:
      Based on antibiograms of 105 cases, a high resistance to Synercid, Nalidixic
      acid, Oxacillin and Teofilin was de-tected whereas the lowest resistance observed
      in Nitrofurantoin, Vancomycin, Linezolid and Teicoplanin antibiotics. CONCLUSION:
      According to the results, Teicoplanin, Vancomycin, Linezolid and Nitrofurantoin
      are recommended against E. faecalis species.

PMID- 23875090
TI  - Direct composite laminate veneers: three case reports.
AB  - Re-establishing a patient's lost dental esthetic appearance is one of the most
      important topics for contemporary dentistry. New treatment materials and methods
      have been coming on the scene, day by day, in order to achieve such an aim. Most
      dentists prefer more conservative and aesthetic approaches, such as direct and
      indirect laminate veneer restorations, instead of full-ceramic crowns for
      anteriors where aesthetics is really important. Laminate veneers are restorations
      which are envisioned to correct existing abnormalities, esthetic deficiencies and
      discolo-rations. Laminate veneer restorations may be processed in two different
      ways: direct or indirect. Direct laminate veneers have no need to be prepared in
      the laboratory and are based on the principle of application of a composite
      material directly to the prepared tooth surface in the dental clinic. Indirect
      laminate veneers may be produced from composite materials or ceramics, which are
      cemented to the tooth with an adhesive resin. In this case report, direct
      composite laminate veneer technique used for three patients with esthetic
      problems related to fractures, discolorations and an old prolapsed restoration,
      is described and six-month follow-ups are discussed. As a conclusion, direct
      laminate veneer restorations may be a treatment option for patients with the
      esthetic problems of anterior teeth in cases similar to those reported here. 

PMID- 23875091
TI  - Simultaneous Replacement of Maxillary Central Incisors with CEREC Biogeneric
      Reference Technique: A Case Report.
AB  - Biogeneric Reference Technique (BRT) of the CEREC 3D v.3.8 software is an
      effective technique for single anterior ceramic crowns because it provides
      computer-controlled match of the tooth form to the contralateral tooth. BRT also
      enables the fabrication of two or more anterior all-ceramic crowns
      simultaneously. This clinical report demonstrates the clinical application of BRT
      for designing and milling two central incisors in one appointment using a single
      optical impression. After completing the virtual design of the first central
      incisor, it was copied and a mirror image was created. The second central incisor
      was designed using this replicated image and therefore a computer-controlled
      symmetry was obtained. The crowns were milled from monolithic feldspathic ceramic
      blocks and adhesively luted with dual-cured resin cement following dentin
      conditioning. At the two-year follow-up appointment, the restorations were
      intact, no adverse effects were noted, and the resultant appearance was highly
      satisfactory for the patient. A step-by-step protocol is described from design to
      cementation of these restorations. 

PMID- 23875092
TI  - Role of lubiprostone on gastrointestinal motility.

PMID- 23875093
TI  - Can electrical stimulation therapy be helpful for patients with chronic
      constipation refractory to biofeedback therapy?

PMID- 23875094
TI  - Evaluation of Esophageal Motor Function With High-resolution Manometry.
AB  - For several decades esophageal manometry has been the test of choice to evaluate
      disorders of esophageal motor function. The recent introduction of high
      resolution manometry for the study of esophageal motor function simplified
      performance of esophageal manometry, and revealed previously unidentified
      patterns of normal and abnormal esophageal motor function. Presentation of
      pressure data as color contour plots or esophageal pressure topography led to the
      development of new tools for analyzing and classifying esophageal motor patterns.
      The current standard and still developing approach to do this is the Chicago
      classification. While this methodical approach is improving our diagnosis of
      esophageal motor disorders, it currently does not address all motor
      abnormalities. We will explore the Chicago classification and disorders that it
      does not address. 

PMID- 23875095
TI  - What indigestion means to the malays?
AB  - Despite being a large ethnic group within the South-East Asia, there is a paucity
      of reported literatures on dyspepsia in the Malay population. Recent population
      based studies indicate that uninvestigated dyspepsia, based on the Rome II
      criteria, is reported in 12.8% and 11.6% of Malays in the urban and rural
      communities respectively. Organic causes of dyspepsia including upper
      gastrointestinal tract cancers, its precancerous lesions, and erosive diseases
      are uncommon which is largely due to an exceptionally low prevalence of
      Helicobacter pylori infection in this population. On the other hand, functional
      dyspepsia and irritable bowel syndrome are relatively common in the Malays than
      expected. Within a primary care setting, functional dyspepsia, based on the Rome
      III criteria, is reported in 11.9% of Malays, of which epigastric pain syndrome
      is found to be more common. Married Malay females are more likely to have
      functional dyspepsia and psychosocial alarm symptoms. Also based on the Rome III
      criteria, irritable bowel syndrome, commonly overlapped with functional
      dyspepsia, is reported in 10.9% of Malays within a community-based setting.
      Rather than psychosocial symptoms, red flags are most likely to be reported among
      the Malays with irritable bowel syndrome despite having a low yield for organic
      diseases. Based upon the above observations, "proton pump inhibitor test" is
      probably preferable than the "test and treat H. pylori" strategy in the initial
      management of dyspepsia among the Malays. 

PMID- 23875097
TI  - Lubiprostone Increases Small Intestinal Smooth Muscle Contractions Through a
      Prostaglandin E Receptor 1 (EP1)-mediated Pathway.
AB  - BACKGROUND/AIMS: Lubiprostone, a chloride channel type 2 (ClC-2) activator, was
      thought to treat constipation by enhancing intestinal secretion. It has been
      associated with increased intestinal transit and delayed gastric emptying.
      Structurally similar to prostones with up to 54% prostaglandin E2 activity on
      prostaglandin E receptor 1 (EP1), lubiprostone may also exert EP1-mediated
      procontractile effect on intestinal smooth muscles. We investigated
      lubiprostone's effects on intestinal smooth muscle contractions and pyloric
      sphincter tone. METHODS: Isolated murine small intestinal (longitudinal and
      circular) and pyloric tissues were mounted in organ baths with modified Krebs
      solution for isometric recording. Basal muscle tension and response to electrical
      field stimulation (EFS; 2 ms pulses/10 V/6 Hz/30 sec train) were measured with
      lubiprostone (10(-10)-10(-5) M) +/- EP1 antagonist. Significance was established
      using Student t test and P < 0.05. RESULTS: Lubiprostone had no effect on the
      basal tension or EFS-induced contractions of longitudinal muscles. With circular
      muscles, lubiprostone caused a dose-dependent increase in EFS-induced
      contractions (2.11 +/- 0.88 to 4.43 +/- 1.38 N/g, P = 0.020) that was inhibited
      by pretreatment with EP1 antagonist (1.69 +/- 0.70 vs. 4.43 +/- 1.38 N/g, P =
      0.030). Lubiprostone had no effect on circular muscle basal tension, but it
      induced a dose-dependent increase in pyloric basal tone (1.07 +/- 0.01 to 1.97 +/
      0.86 fold increase, P < 0.05) that was inhibited by EP1 antagonist. CONCLUSIONS:
      In mice, lubiprostone caused a dose-dependent and EP1-mediated increase in
      contractility of circular but not longitudinal small intestinal smooth muscles,
      and in basal tone of the pylorus. These findings suggest another mechanism for
      lubiprostone's observed clinical effects on gastrointestinal motility.

PMID- 23875096
TI  - Irritable bowel syndrome and migraine: bystanders or partners?
AB  - Irritable bowel syndrome (IBS) and migraine are distinct clinical disorders.
      Apart from the characteristics of chronic and recurrent pain in nature, these
      pain-related disorders apparently share many similarities. For example, IBS is
      female predominant with community prevalence about 5-10%, whereas that of
      migraine is 1-3% also showing female predominance. They are often associated with
      many somatic and psychiatric comorbidities in terms of fibromyaglia, chronic
      fatigue syndrome, interstitial cystitis, insomnia and depression etc., even the
      IBS subjects may have coexisted migraine with an estimated odds ratio of 2.66.
      They similarly reduce the quality of life of victims leading to the social,
      medical and economic burdens. Their pathogeneses have been somewhat addressed in
      relation to biopsychosocial dysfunction, heredity, genetic polymorphism,
      central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain
      network, gonadal hormones and abuses etc. Both disorders are diagnosed according
      to the symptomatically based criteria. Multidisciplinary managements such as
      receptor target new drugs, melantonin, antispasmodics, and psychological drugs
      and measures, complementary and alternatives etc. are recommended to treat them
      although the used agents may not be necessarily the same. Finally, the prognosis
      of IBS is pretty good, whereas that of migraine is less fair since suicide
      attempt and stroke are at risk. In conclusion, both distinct chronic pain
      disorders to share many similarities among various aspects probably suggest that
      they may locate within the same spectrum of a pain-centered disorder such as
      central sensitization syndromes. The true pathogenesis to involve these disorders
      remains to be clarified in the future. 

PMID- 23875098
TI  - An evidence of esophageal decompensation in patients with achalasia in the view
      of its subtype: a retrospective study.
AB  - BACKGROUND/AIMS: Achalasia is a primary motility disorder of esophagus. Many
      parameters represent esophageal function and morphologic changes, but their
      interrelationship is not yet established. We hypothesized that esophageal body
      would need to generate unusual pressure to empty the food bolus through the non
      relaxing lower esophageal sphincter in patients with achalasia; therefore, higher
      is the residual lower esophageal sphincter pressure, greater would be the
      contraction pressure in the esophageal body in these patients. To verify the
      hypothesis, correlations among parameters from esophageal manometry,
      esophagography and esophageal transit study had been investigated. METHODS: A
      retrospective review of 34 patients was conducted. Resting lower esophageal
      sphincter pressure and contraction pressure of esophageal body were obtained from
      conventional esophageal manometry. Diameter of esophageal body was measured from
      barium column under esophagography. Radionuclide imaging was performed to assess
      the esophageal transit, designated as R30, which was the residual radioactivity
      at 30 seconds after ingesting radioactive isotope. RESULTS: In vigorous achalasia
      group, contraction pressure of esophageal body was negatively correlated to
      dilated diameter of esophageal body (P = 0.025, correlation coefficient = 
      0.596). Esophageal transit was more delayed as dimensions of esophageal body
      increased in classic achalasia group (P = 0.039, correlation coefficient =
      0.627). CONCLUSIONS: Diameter of esophageal body in classic achalasia was
      relatively wider than that of vigorous achalasia group and the degree of delayed
      esophageal transit was proportionate to the luminal widening. Patients with
      vigorous achalasia had narrower esophageal lumen and relatively shorter transit
      time than that of classic achalasia group. Proper peristalsis is not present in
      achalasia patients but remaining neuromuscular activity in vigorous achalasia
      patients might have caused the luminal narrowing and shorter transit time.

PMID- 23875099
TI  - Relevance of ultrastructural alterations of intercellular junction morphology in
      inflamed human esophagus.
AB  - BACKGROUND/AIMS: Detailed characterization of the ultrastructural morphology of
      intercellular space in gastroesophageal reflux disease has not been fully
      studied. We aimed to investigate whether subtle alteration in intercellular space
      structure and tight junction proteins might differ among patients with
      gastroesophageal reflux disease. METHODS: Esophageal biopsies at 5 cm above the
      gastroesophageal junction were obtained from 6 asymptomatic controls, 10 patients
      with reflux symptoms but without erosions, and 18 patients with erosions. The
      biopsies were morphologically evaluated by transmission electron microscopy, and
      by using immunohistochemistry for tight junction proteins (claudin-1 and claudin
      2 proteins). RESULTS: The expressions of tight junction proteins did not differ
      between asymptomatic controls and gastroesophageal reflux disease patients. In
      patients with gastroesophageal reflux disease, altered desmosomal junction
      morphology was only found in upper stratified squamous epithelium. Dilated
      intercellular space occurred only in upper stratified squamous epithelium and in
      patients with erosive esophagitis. CONCLUSIONS: This study suggests that dilated
      intercellular space may not be uniformly present inside the esophageal mucosa and
      predominantly it is located in upper squamous epithelium. Presence of desmosomal
      junction alterations is associated with increased severity of gastroesophageal
      reflux disease. Besides dilated intercellular space, subtle changes in
      ultrastructural morphology of intercellular space allow better identification of
      inflamed esophageal mucosa relevant to acid reflux.

PMID- 23875100
TI  - Specific movement of esophagus during transient lower esophageal sphincter
      relaxation in gastroesophageal reflux disease.
AB  - BACKGROUND/AIMS: Transient lower esophageal sphincter relaxation (TLESR) is the
      main mechanism of gastroesophageal reflux disease (GERD). The aim of this study
      was to investigate the characteristics of transient lower esophageal sphincter
      movement in patients with or without gastroesophageal reflux by high-resolution
      manometry (HRM). METHODS: From June 2010 to July 2010, we enrolled 9 patients
      with GERD (GERD group) and 9 subjects without GERD (control group),
      prospectively. The manometry test was performed in a semi-recumbent position for
      120 minutes following ingestion of a standardized, mixed liquid and solid meal.
      HRM was used to identify the frequency and duration of TLESR, esophageal
      shortening length from incomplete TLESR, upper esophageal sphincter (UES)
      response, and the related esophageal motor responses during TLESR. RESULTS: TLESR
      occurred in 33 in the GERD group and 34 in the control group after 120 minutes
      following food ingestion. Duration of TLESR and length of esophageal shortening
      did not differ between 2 groups. UES pressure increase during TLESR was mostly
      detected in patients with GERD, and UES relaxation was observed frequently in the
      control group during TLESR. TLESR-related motor responses terminating in TLESR
      were predominantly observed in the control group. CONCLUSIONS: Increased UES
      pressure was noted frequently in the GERD group, suggesting a mechanism for
      preventing harmful reflux, which may be composed mainly of fluid on the larynx or
      pharynx. However, patients with GERD lacked the related motor responses
      terminating in TLESR to promote esophageal emptying of refluxate.

PMID- 23875101
TI  - Obesity is associated with increasing esophageal Acid exposure in korean patients
      with gastroesophageal reflux disease symptoms.
AB  - BACKGROUND/AIMS: Obesity is regarded as an important contributor to the
      increasing occurrence of gastroesophageal reflux disease. The aims of this study
      were to determine whether obesity is associated with gastroesophageal reflux in
      patients with gastroesophageal reflux disease and to identify the factors
      affecting increased acid exposure in obese patients. METHODS: We retrospectively
      analyzed the data of patients who underwent ambulatory 24-hour pH monitoring and
      esophageal manometry at Seoul St. Mary's Hospital. Obesity was classified
      according to the Asia-Pacific criteria. RESULTS: A total of 366 patients were
      analyzed; 18 were underweight, 152 normal weight, 104 overweight, and 92 obese.
      Obesity was more frequent in men and younger patients. The percentage time of pH
      < 4 in the total, upright, and postprandial periods was significantly higher in
      obese patients than in normal or underweight patients. The DeMeester score was
      also higher in obese patients. Body mass index correlated positively with reflux
      parameters. Multivariate analysis showed that being male and obesity were
      significantly associated with abnormal acid exposure (P < 0.005). The total lower
      esophageal sphincter length shortened as body mass index increased (P < 0.005).
      The gastroesophageal pressure gradient increased as body mass index increased (P
      < 0.05). CONCLUSIONS: Obesity is associated with increasing esophageal acid
      exposure. The mechanism responsible for the relationship between gastroesophageal
      reflux disease and obesity may be associated with shortening of the lower
      esophageal sphincter length and increasing the gastroesophageal pressure
      gradient.

PMID- 23875102
TI  - Association of sleep dysfunction and emotional status with gastroesophageal
      reflux disease in Korea.
AB  - BACKGROUND/AIMS: Sleep disturbances and emotional dysfunction are commonly
      associated with gastroeophageal reflux disease (GERD). The aims of this study
      were to evaluate GERD symptoms and disturbance in erosive reflux disease (ERD)
      and nonerosive reflux disease (NERD) patients, and to compare sleep dysfunction,
      depressive mood, anxiety and quality of life (QOL) among the control, ERD and
      NERD patients in Korea. METHODS: The Korean subjects were enrolled between 2010
      and 2012, classified into 3 groups; the control group with no symptom and normal
      endoscopic findings, the ERD group with erosive esophagitis and the NERD group
      with more than one episode of heartburn or acid regurgitation per week, positive
      response to proton pump inhibitor, and normal endoscopic findings. Questionnaire
      included GERD symptoms, GERD impact scale (GIS) and daytime pathological
      sleepiness (Epworth sleepiness scale), sleep dysfunction (Pittsburgh sleep
      quality index, PSQI), depression and anxiety (Hospital anxiety and depression
      scale, HADS) and QOL (WHO quality of life scale abbreviated version, WHOQOL
      BREF). RESULTS: A total of 217 subjects were enrolled as follows; control (n =
      70), ERD (n = 70) and NERD (n = 77). Impact of symptom of GIS score was higher in
      the NERD (9.2 +/- 0.4) than in the ERD (6.5 +/- 0.3) group (P < 0.001). Sleep
      dysfunctions were more frequent in GERD than the control group (PSQI score [P =
      0.021]). Anxiety subscale of HAD score was higher in NERD (7.0 +/- 0.5, P =
      0.002) and ERD (6.2 +/- 0.7, P = 0.004) groups than control (4.3 +/- 0.7) group.
      WHOQOL-BREF scores in NERD (54.9 +/- 2.3) and ERD (57.8 +/- 2.4) groups were
      significantly lower than those in the control group (63.8 +/- 2.4) (P = 0.002; P
      = 0.014, respectively). CONCLUSIONS: The patients with NERD than ERD suffered
      more from the symptoms and disturbance in Korea. Sleep dysfunction and anxiety
      mood were higher and QOL was decreased in GERD, especially in NERD, suggesting
      that those factors might affect the severity of NERD.

PMID- 23875103
TI  - Gastric motility following ingestion of a solid meal in a cohort of adult
      asthmatics.
AB  - BACKGROUND/AIMS: Asthmatics have abnormal esophageal motility and increased
      prevalence of gastroesophageal reflux disease (GERD). The contribution of gastric
      motility is less studied. We studied gastric myoelectrical activity, gastric
      emptying (GE) and their association with GERD symptoms and vagal function in
      adult asthmatics. METHODS: Thirty mild, stable asthmatics and 30 healthy controls
      underwent real-time ultrasonography and 1 hour pre- and post-prandial cutaneous
      electrogastrography, following a test meal (480 kcal, 60% carbohydrate, 20%
      protein, 20% fat and 200 mL water). The percentage of normal slow waves and
      arrhythmias, dominant frequency and power, frequency of antral contractions,
      gastric emptying rate (GER) and antral motility index (MI) was calculated. Twenty
      seven asthmatics underwent gastroscopy and in all subjects GERD symptoms were
      assessed by a validated questionnaire. Vagal function parameters were correlated
      with gastric motility parameters. RESULTS: The asthmatics (37% male; 34.8 +/- 8.4
      years) and controls (50% male; 30.9 +/- 7.7 years) were comparable. None had
      endoscopic gastric pathological changes. Twenty asthmatics described GERD
      symptoms. Twenty-two (73.3%) asthmatics showed a hypervagal response. Compared to
      controls, asthmatics had delayed GER and lower MI, lower percentage of normal
      gastric slow waves, more gastric dysrythmias and failed to increase the post
      prandial dominant power. There was no correlation of GE and cutaneous
      electrogastrography parameters with presence of GERD symptoms or with vagal
      function. CONCLUSIONS: Asthmatics showed abnormal gastric myoelectrical activity,
      delayed GE and antral hypomotility in response to a solid meal compared to
      controls. There was no association with vagal function or GERD symptom status.

PMID- 23875104
TI  - Electrical stimulation therapy in chronic functional constipation: five years'
      experience in patients refractory to biofeedback therapy and with rectal
      hyposensitivity.
AB  - BACKGROUND/AIMS: Biofeedback therapy (BFT) can be unsuccessful in constipated
      patients, even those with pelvic floor dysfunction. Electrical stimulation
      therapy (EST) has been introduced as a novel therapeutic modality in patients
      with chronic constipation, especially those who have rectal hyposensitivity. We
      evaluated the efficacy of EST based on five years' clinical experience. METHODS:
      From January 2002 to February 2007, 159 patients underwent EST. After exclusion
      of 12 drop-outs, 147 (M:F = 61:86, 49 +/- 17 years) finished all treatment
      sessions. Among them, 88 (M:F = 29:59, 49 +/- 17 years) were refractory to BFT
      without rectal hyposensitivity (RH), and 59 (M:F = 32:27, 54 +/- 17 years) were
      those with RH. RESULTS: The overall response to EST was 59.2% (87/147) by per
      protocol analysis. In the EST-responsive group, overall satisfaction improved
      significantly (from 7.3 +/- 3.0 to 4.3 +/- 2.5, P < 0.05). Subgroup analysis
      showed that the response rate was 64.8% (57/88) in patients refractory to BFT
      without RH, and 50.8% (30/59) in those with RH. CONCLUSIONS: EST may have
      additional therapeutic efficacy in patients who are refractory to BFT. EST may
      also be effective in patients with RH, including restoration of rectal sensation.
      Therefore, EST could be considered as an alternative choice in patients
      refractory to BFT and with or without RH.

PMID- 23875105
TI  - Defecation frequency and stool form in a coastal eastern Indian population.
AB  - BACKGROUND/AIMS: Data on normal stool form and frequency, which are important for
      defining constipation, are scanty; hence, we studied these in an eastern Indian
      population. METHODS: One thousand and two hundred apparently healthy asymptomatic
      subjects were evaluated for predominant stool form (Bristol chart with
      descriptor) and frequency. Data on demographic and life-style (diet and physical
      activity) were collected. RESULTS: Of 1,200 subjects (age 42 +/- 14.5 years, 711,
      59% male), most passed predominantly Bristol type IV stool (699 [58.2%]; other
      forms were: type I (23 [1.9%]), type II (38 [3.2%]), type III (99 [8.2%]), type V
      (73 [6%]), type VI (177 [14.7%]), type VII (7 [0.6%]) and an irregular
      combination (84 [7%]). Weekly stool frequency was 12.1 +/- 4.7 (median 14, range
      2-42). Less than 3 stools/week was noted in 32/1,200 (2.6%). Female subjects (n =
      489) passed stools less frequently than males (n = 711) (11.1 +/- 5.6/week vs.
      12.8 +/- 3.8/week, P < 0.001) and tended to pass harder forms (type I: 17, type
      II: 20, type III: 39 vs. 6, 18 and 60, respectively, P = 0.061). Vegetarians (n =
      252) and physically active (n = 379) subjects tended to pass stool more
      frequently than occasional (n = 553) and regular non-vegetarian (n = 395) (11.8
      +/- 4.5 and 12.8 +/- 4.7 vs. 11.3 +/- 4.7; P < 0.05) and sedentary (n = 464) and
      intermediately active (n = 357) subjects (13.4 +/- 4.0 and 12.3 +/- 4.5 vs. 10.9
      +/- 5.1, P = 0.080) in different age groups, respectively. Older age was
      associated with less frequent stool, particularly among female population. Female
      gender and age > 35 years were significant on multivariate analysis. CONCLUSIONS:
      Median stool frequency in the studied population was 14/week (range 2-42) and
      predominant form was Bristol type IV. Older age was associated with lesser stool
      frequency, particularly among female subjects.

PMID- 23875106
TI  - Regional differences in hospitalizations and cholecystectomies for biliary
      dyskinesia.
AB  - BACKGROUND/AIMS: Published studies suggest that socioeconomic factors contribute
      to increasing cholecystectomy rates for biliary dyskinesia (BD). The aim of this
      study was to identify factors driving admissions and operations for BD by
      examining regional variability in hospitalizations and cholecystectomies for this
      disorder. METHODS: Annual hospitalizations and cholecystectomy rates for biliary
      diseases were assessed using the State Inpatient Databases of the Agency for
      Healthcare Research and Quality based on diagnosis codes for biliary dyskinesia,
      cholecystolithiasis and cholecystitis. RESULTS: Annual admissions for BD varied
      nearly sevenfold among different states within the United States.
      Hospitalizations for gallstone disease and its complication showed less
      variability, differing 2-fold between states. Nearly 70% of admissions for BD and
      about 85% of admissions for gallstone disease resulted in cholecystectomies.
      Higher admission rates for BD were best predicted by high overall hospitalization
      rates, admission rate for gallstone disease and the physician workforce within a
      state. Cholecystectomy rates for BD were higher in states with low population
      density and high rates of cholecystectomy for gallstone disease. CONCLUSIONS:
      These data suggest that established medical practice patterns significantly
      contribute to the variability in admissions and operations for biliary
      dyskinesia. The findings also indicate that lower thresholds for operative
      interventions are an important determinant in the approach to this disorder.
      Considering the benign course of functional illnesses, the bar for surgical
      interventions should be raised rather than lowered; in addition active
      conservative treatment options should be developed for these patients.

PMID- 23875107
TI  - Lung transplantation triggered "jackhammer esophagus": a case report and review
      of literature.
AB  - A 19-years-old girl was referred for lung transplant due to end stage lung
      disease secondary to idiopathic bilateral bronchiectasis. Her routine pre lung
      transplant evaluation showed normal esophageal high-resolution manometry (HRM)
      and 24-hours impedance pH monitoring. Four weeks after the bilateral sequential
      lung transplantation (LTx), she developed dysphagia, chest pain and
      regurgitation, complicated by aspiration pneumonia. Repeated HRM showed
      Jackhammer esophagus, delayed gastric emptying and abnormal 24-hour pH impedance
      monitoring consistent with the diagnosis of gastroesophageal reflux disease.
      Twelve weeks after LTx, she was symptom free, HRM and 24-hour impedance pH
      monitoring returned to normal. To the best of our knowledge, this rare transient
      esophageal hypercontractility episode occurred after LTx and recovered without
      any specific treatment was never reported in literature. The etiopathogenesis of
      Jackhammer esophagus in general and LTx induced dysmotility in particular is
      discussed and reviewed. 

PMID- 23875109
TI  - Successful surgical repair of anterior rectocele in patient with constipation.

PMID- 23875108
TI  - Technique of functional and motility test: how to perform antroduodenal
      manometry.
AB  - Antroduodenal manometry is one of the methods to evaluate stomach and duodenal
      motility. This test is a valuable diagnostic tool for gastrointestinal motility
      disorders especially small intestinal pseudo-obstruction which is difficult to
      make definite diagnosis by clinical manifestations or radiologic findings.
      Manometric findings that have no evidence of mechanical obstruction and
      suggestive of pseudo-obstruction with neuropathy or myopathy can avoid
      unnecessary surgery and the treatment can be directly targeted. Moreover, among
      patients who have clinically suspected small intestinal pseudo-obstruction but
      with normal manometric findings, the alternative diagnosis including psychiatric
      disorder or other organic disease should be considered. The application of this
      test to the patients with functional gastrointestinal symptoms especially to find
      the association of motor abnormalities to the symptom has less impressive yield.
      Antroduodenal manometry is now readily available only in some tertiary care
      centers. The aim of this review is to describe the antroduodenal manometry
      technique, interpretation and clinical utility. 

PMID- 23875110
TI  - Extremely High Panesophageal Pressurization in Type II Achalasia.

PMID- 23875111
TI  - Overlap between postprandial distress and epigastric pain syndromes in functional
      dyspepsia: its implications for research and clinical practice (am j
      gastroenterol 2013;108:767-774).

PMID- 23875112
TI  - Should Acid suppressive therapy improve chronic cough? (Chest 2013;143:605-612).

PMID- 23875113
TI  - Interpretation of a manometric trace of the upper esophageal sphincter.

PMID- 23875114
TI  - Role of Helicobacter pylori in Functional Dyspepsia: More Controversies Than
      Answers.

PMID- 23875115
TI  - Psychosocial factors and rectal hyposensitivity.

PMID- 23875117
TI  - Evidence-Based Practice and Chiropractic Care.
AB  - Evidence-based practice has had a growing impact on chiropractic education and
      the delivery of chiropractic care. For evidence-based practice to penetrate and
      transform a profession, the penetration must occur at 2 levels. One level is the
      degree to which individual practitioners possess the willingness and basic skills
      to search and assess the literature. Chiropractic education received a
      significant boost in this realm in 2005 when the National Center for
      Complementary and Alternative Medicine awarded 4 chiropractic institutions R25
      education grants to strengthen their research/evidence-based practice curricula.
      The second level relates to whether the therapeutic interventions commonly
      employed by a particular health care discipline are supported by clinical
      research. A growing body of randomized controlled trials provides evidence of the
      effectiveness and safety of manual therapies.

PMID- 23875116
TI  - Adenocarcinomas After Prophylactic Surgery For Familial Adenomatous Polyposis.
AB  - The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000
      live births. Virtually, all surgically untreated patients with FAP inevitably
      develop colorectal-cancer in their lifetime because they carry the adenomatous
      polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical
      treatment of FAP is still controversial. There are however, four surgical
      options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch
      anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with
      continent-ileostomy. Conventional proctocolectomy options largely lie between
      colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors
      of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better
      functional results and quality of life. The functional outcome of total colectomy
      with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal
      pouch; however, the risk for rectal cancer is increased by 30%. Even after
      mucosectomy, inadvertent small mucosal residual islands remain. These residual
      islands carry the potential for the development of subsequent malignancy. We
      reviewed the literature (1975-2012) on the incidence, nature, and possible
      etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after
      prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92
      pouch-related cancers; 15 case reports, 4 prospective and 5 retrospective
      studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69
      (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance
      and treatment are presented. Data suggest lifetime surveillance of these
      patients.

PMID- 23875118
TI  - Oral rehydration solutions for burn management in the field and underdeveloped
      regions: a review.
AB  - Burn injuries are the fourth most common type of trauma worldwide, and the
      appropriate care of burn injuries in resource-limited settings such as the
      battlefield, underdeveloped nations, or in mass casualtiesremains a significant
      challenge. Rehydration constitutes the primary treatment of the systemic effects
      of burns and is a major factor in patient recovery. The standard of care for the
      replenishment of fluid and electrolyte losses in burn injury remains intravenous
      fluid therapy, but oral rehydration solution therapy (ORST) demonstrates
      beneficial utility in saving the lives of burn patients when they are applied in
      the acute phase of burn injuries, especially when intravenous rehydration is
      unavailable or inaccessible. Advantages of ORST as compared to intravenous
      therapy include availability, ease of administration in the field, low risk of
      infections and complications, low cost, and no requirement for accessory or
      specialized equipment. These benefits position ORST very attractively for the
      provision of interim first aid until definitive medical assistance arrives.
      Extensive and comprehensive investigation may be warranted to elucidate, account
      for and quantify individual burn patient biochemical variables toward the
      potential realization of such an "omniuse" oral rehydration solution for the
      benefit of burn injuries worldwide. 

PMID- 23875119
TI  - Can we use C-reactive protein levels to predict severe infection or sepsis in
      severely burned patients?
AB  - This is a large cohort analysis in severely burned pediatric children to
      determine whether C-reactive protein (CRP) can be used as a predictor for severe
      infection or sepsis. Nine-hundred eighteen pediatric burn patients were enrolled
      in this study. CRP values were measured throughout acute hospitalization and for
      up to 6 months postburn. Demographic data, incidence of infection, surgical
      interventions and other relevant clinical information was compiled from medical
      records. We performed an extensive literature search to identify models that
      other groups have developed to determine the effects of CRP levels postburn to
      assess the value of these parameters as predictors of sepsis or severe infection.
      Statistical analysis was performed using ANOVA and regression analysis where
      appropriate. Three-hundred fifteen female and 603 male pediatric patients were
      enrolled in this study. Average total body surface area (TBSA) burn was 45+/-23%,
      with full thickness burn over 32+/-27% TBSA, and patients were 7+/-6 years old.
      CRP values significantly correlated with burn size, survival and gender.
      Significantly higher levels of CRP were found in large burns, in non-survivors,
      and in females, p<0.05. Using various described models to determine whether CRP
      levels change before and after an event can predict sepsis or severe infection,
      we found that CRP cannot predict severe infection or sepsis. Although CRP is a
      marker of the inflammatory response postburn, CRP fails to predict infection or
      sepsis in severely burn patients. 

PMID- 23875120
TI  - The feasibility of tissue expansion in reconstruction of congenital and aquired
      deformities of pediatric patients.
AB  - Skin expansion is one of the major developments in reconstructive surgery. The
      use of tissue expansion has been popularized among plastic surgeons and has
      become the treatment method of choice for many congenital and acquired defects in
      a wide variety of diseases in adults and then later in children. The authors
      analyze their clinical experience in the treatment of burn scars and complex
      defects by tissue expansion in pediatric patients. The study included thirty five
      expansion procedures performed in 25 patients. Smooth surface expanders with a
      remote valve were used in the scalp (22), face (2), neck (3), hand (2), thorax
      (2), breast (1), palate (2), abdomen (1). Self-inflating osmotic tissue expanders
      were used in four patients, one of them had cleft palate and the other two of
      them had congenital hand anomalies and the last one had frontal scar and alopecia
      in the frontal hairline. In 19 out of 25 cases (76%) tissue expansion was
      achieved without complications. At the same time, in 1 cases minor complications
      and in 5 cases major complications occurred. The number of expanders per patient
      was only one in 16 cases. More than one expander was used to remove parts of the
      same injury in 9 cases. Our study may help to draw attention again on different
      aspects in tissue expansion and critically focus on each step of the tissue
      expansion both using self-filling tissue expanders and smooth surface tissue
      expanders with a remote valve. 

PMID- 23875121
TI  - Pediatric burns mortality risk factors in a developing country's tertiary burns
      intensive care unit.
AB  - AIM: This study aimed at identifying risk factors related to pediatric burns
      mortality in a middle income country such as Ghana. METHODS: The data for the
      three years retrospective study (May 2009 - April 2012) was obtained from the
      pediatric burn admissions records and patients' folders of the Reconstructive
      Plastic Surgery & Burns Unit (RPSBU), Komfo Anokye Teaching Hospital (KATH),
      Ghana. Data retrieved included: Demographic features, Total Burned Surface Area
      (TBSA) incurred; Aetiology of burns; Duration of the admission; Outcome of
      admission; Part of the body affected and Cost incurred. Ethical approval for this
      study was obtained from the KNUST-SMS/KATH Committee on Human Research,
      Publications and Ethics. Data analyses were performed with SPSS 17.0 version.
      RESULTS: Information on 197 patients was completely retrieved for the study.
      Burns mortality rate for the study was identified to be 21.3% (N=42). The mean
      age of the 42 dead patients was 3.7+/-0.3 years, ranging from 0-13 years, while,
      males (54.8%, N= 23) outnumbered females (45.2%, N=19). The TBSA burned
      interquartile range was 48%. In terms of etiology of burns Scald (73.8%, N=31)
      was the commonest cause of injury. Mortality risk factors identified were Age <6
      years (P=0.028); Scald especially hot water and soup (P=0.016); TBSA >36%
      (P=0.028) and Inhalation injury (P=0.040). CONCLUSION: Age, scald, TBSA and
      Inhalation Injury were identified as pediatric burns mortality risk factors in a
      developing country such as Ghana's RPSBU. These identified factors will serve as
      a guideline for plastic surgeons and other health professionals practicing in
      countries such as Ghana.

PMID- 23875122
TI  - Serum albumin levels in burn people are associated to the total body surface
      burned and the length of hospital stay but not to the initiation of the
      oral/enteral nutrition.
AB  - OBJECTIVE: Serum albumin levels have been used to evaluate the severity of the
      burns and the nutrition protein status in burn people, specifically in the
      response of the burn patient to the nutrition. Although it hasn't been proven if
      all these associations are fully funded. The aim of this retrospective study was
      to determine the relationship of serum albumin levels at 3-7 days after the burn
      injury, with the total body surface area burned (TBSA), the length of hospital
      stay (LHS) and the initiation of the oral/enteral nutrition (IOEN). SUBJECT AND
      METHODS: It was carried out with the health records of patients that accomplished
      the inclusion criteria and were admitted to the burn units at the University
      Hospital of Reina Sofia (Cordoba, Spain) and UAB Hospital at Birmingham (Alabama,
      USA) over a 10 years period, between January 2000 and December 2009. We studied
      the statistical association of serum albumin levels with the TBSA, LHS and IOEN
      by ANOVA one way test. The confidence interval chosen for statistical differences
      was 95%. Duncan's test was used to determine the number of statistically
      significantly groups. RESULTS: Were expressed as mean+/-standard deviation. We
      found serum albumin levels association with TBSA and LHS, with greater to lesser
      serum albumin levels found associated to lesser to greater TBSA and LHS. We
      didn't find statistical association with IOEN. CONCLUSION: We conclude that serum
      albumin levels aren't a nutritional marker in burn people although they could be
      used as a simple clinical tool to identify the severity of the burn wounds
      represented by the total body surface area burned and the lenght of hospital
      stay.

PMID- 23875123
TI  - Pattern and treatment of mandible body fracture.
AB  - The aim of this research was to study of treatment of mandibular body fractures
      (MBF). A retrospective study of 66 patients with mandibular body fracture was
      realized with subjects was present clinical and image diagnosis;were analyzed
      socio-demographic variables, etiology, sign and symptoms of fracture, type of
      treatment and complications. Was executed a statistical and descriptive analysis
      with Chi-square with statistical significance with p<0.05. The average age was 34
      year with 55 male patient; the more common etiology were physical violence and
      motorcycle accident. The 45.5% present only MBF; patients with multiple fractures
      show clinical relations between MBF and contra lateral mandibular angle fracture;
      54 patients were treated with open reduction without statistical relations with
      symptoms (p=0.244) or displacement of fracture (p=0.309); the 54.2% of surgical
      cases present an extraoral approach, using the intraoral approach when the
      fracture present poor displacement (p=0.0074); the complications more common were
      suture dehiscence and infections of surgical site. We conclude that the initial
      choose of treatment was not related to variables analyzed; when exist a minor
      displacement of MBF can be indicated an intraoral approach for reduction and
      fixation technique. 

PMID- 23875124
TI  - Risk of burn trauma during circumcision with radiofrequency scalpel: case report
      and review of literature.
AB  - Male circumcision, one of the oldest and most frequent operations performed all
      over the world, removes 33-50% of the penile skin. Like each surgical procedure,
      circumcision can leads to complications ranging from the insignificant to the
      tragic. Circumcision methods can be done with different ways. The radiofrequency
      (RF) scalpel, an innovative instrument, can be used in circumcision. Here, we
      present three boys who sustained sever burn injuries during circumcision with RF
      method. In sum, interesting characteristics made RF procedures so popular in
      different fields of surgery. Although having low incidence, the important
      complications of this technology such as burns should raise our attentions.
      Performing radiofrequency circumcision by an experienced operator, selection of
      proper size of ground pads, and elimination of any interface between the skin and
      ground pad are the factors that can prevent such tragedies. 

PMID- 23875125
TI  - A teaching learning based optimization based on orthogonal design for solving
      global optimization problems.
AB  - In searching for optimal solutions, teaching learning based optimization (TLBO)
      (Rao et al. 2011a; Rao et al. 2012; Rao & Savsani 2012a) algorithms, has been
      shown powerful. This paper presents an, improved version of TLBO algorithm based
      on orthogonal design, and we call it OTLBO (Orthogonal Teaching Learning Based
      Optimization). OTLBO makes TLBO faster and more robust. It uses orthogonal design
      and generates an optimal offspring by a statistical optimal method. A new
      selection strategy is applied to decrease the number of generations and make the
      algorithm converge faster. We evaluate OTLBO to solve some benchmark function
      optimization problems with a large number of local minima. Simulations indicate
      that OTLBO is able to find the near-optimal solutions in all cases. Compared to
      other state-of-the-art evolutionary algorithms, OTLBO performs significantly
      better in terms of the quality, speed, and stability of the final solutions. 

PMID- 23875126
TI  - Two-domain mechanics of a spherical, single chamber heart with applications to
      specific cardiac pathologies.
AB  - Continuum approximations of tissue consider responses averaged over many cells in
      a region. This simplified approach allows consideration of macroscopic effects,
      such as deformation or action potential propagation. A bidomain (sometimes known
      as biphasic) approach retains the macroscopic character of a continuum
      approximation while allowing one to consider microscopic effects; novel behavior
      arising from interactions between the intracellular and extracellular spaces can
      also be noted. I consider a spherical, single chamber heart with the new
      mechanical bidomain model in four separate pathologies: hypertension, hypovolemic
      hypotension, and hypertrophic and dilational cardiomyopathies. Analytic solutions
      of intracellular and extracellular displacements and hydrostatic pressures are
      presented; the distributions describe elastic deformation and hydrostatic fluid
      pressure buildup of the extracellular collagen matrix and the intracellular
      muscle under simplified spherical geometry. Potential applications, such as
      stretch activated membrane channels, are also noted. 

PMID- 23875127
TI  - A simple set of validation steps identifies and removes false results in a
      sandwich enzyme-linked immunosorbent assay caused by anti-animal IgG antibodies
      in plasma from arthritis patients.
AB  - Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are chronic diseases
      characterized by activation of the immune system and production of antibodies.
      Thus, rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies
      in plasma samples from arthritis patients can interfere with immunoassays such as
      sandwich enzyme-linked immunosorbent assay (ELISA) systems often used in
      arthritis research. However, standard methodologies on how to test for false
      results caused by these antibodies are lacking. The objective of this study was
      to design a simple set of steps to validate a sandwich ELISA before using it for
      measuring analytes in plasma from arthritis patients. An interleukin-24 (IL-24)
      sandwich ELISA system was prepared with a monoclonal mouse capture antibody and a
      polyclonal goat detection antibody and tested for interference by rheumatoid
      factor, anti-animal IgG antibodies and heterophilic antibodies. Plasma samples
      from 23 patients with RA and SpA were used. No differences were found between
      plasma samples measured in wells coated with anti-IL-24 specific antibody and in
      wells coated with isotype control antibody (false positive results), and
      recombinant human IL-24 was not recovered in spiked samples (false negative
      results). This interference was removed after preincubating the plasma samples
      from patients with arthritis with goat or bovine IgG, suggesting that anti-animal
      IgG antibodies found in the plasma of the arthritis patients caused the false
      results. Additional testing showed that the signal-to-noise ratio could be
      increased by titration of the capture and detection antibodies and by using the
      ELAST amplification system. Finally, the calculated concentration of IL-24 was
      increased in ethylenediaminetetraacetic acid (EDTA) plasma compared to heparin
      plasma and serum and decreased with repetitive freeze/thaw cycles of the samples
      illustrating how sample handling could additionally contribute to the variations
      reported by different laboratories in measurement of the same analyte. This study
      proposes a simple set of validation steps to evaluate and optimize a sandwich
      ELISA before using it for measuring analytes in plasma from arthritis patients.
      Anti-animal IgG antibodies are also present in healthy individuals, suggesting
      that validation of ELISA systems for measuring non-arthritis samples could also
      be improved by this simple set of validation steps. 

PMID- 23875128
TI  - Heterologous expression, immunochemical and computational analysis of recombinant
      human interferon alpha 2b.
AB  - Interferon alpha 2b (IFNalpha-2b) is an important cytokine and used for antiviral
      and anticancer treatment. The low cost production of IFNalpha-2b with high
      biological activity is necessary to provide the interferon therapy to the
      hepatitis patients in Pakistan. In the present study, human interferon alpha 2b
      (hIFNalpha-2b) gene from a healthy person was cloned and overexpressed in E. coli
      BL21(DE3). The molecular weight of the expressed hIFNalpha-2b is 19 kDa. The over
      expressed recombinant hIFNalpha-2b was checked by ELISA using antibodies raised
      against commercially available hIFNalpha-2b. The biocomputational analysis of
      recombinant hIFNalpha-2b gene showed the 99.9% nucleotide sequence and 100%
      deduced amino acid sequence homology with reported sequences of IFNalpha-2b. The
      predicted 3D-structure showed mainly five alpha-helices, one 310 helix and two
      disulfide bonds at Cys1-Cys98 and Cys129-Cys138. The amino acid sequence
      alignment indicated that the disulfide linkage position is conserved in all
      IFNalpha family members. On the basis of sequence homology among interferon alpha
      family, new potent variants of hIFNalpha-2b with enhance efficacy can be
      produced. Indigenous production of IFNalpha-2b from gene of local population will
      reduce the cost and increase tolerability of interferon therapy. 

PMID- 23875130
TI  - Investigations on juvenile fish excluder cum shrimp sorting device (JFE-SSD).
AB  - Penaeid shrimp is a major resource in India contributing about 7.4% of the total
      marine fish landings. They are mostly landed by small mechanized trawlers. Shrimp
      trawling generates large quantities of bycatch mostly consisting of juvenile
      fishes, due to use of small mesh size in codends of trawl nets. Juvenile Fish
      Excluder cum Shrimp Sorting Device (JFE-SSD) is a bycatch reduction device with
      an in situ sorting mechanism, which replaces the conventional codend in a trawl.
      The device was designed to catch shrimps and commercially important fish species
      using a specially designed oval sorting grid with appropriate bar spacing and
      dual codends. Shrimp sorting efficiency and bycatch exclusion characteristics of
      JFE-SSD attached to a 29.6 m shrimp trawl, was tested by experimental fishing
      along the coastal waters off Cochin, India. Out of a total of 317.07 kg of catch
      encountered in the JFE-SSD installed trawl, 58.22% was retained in lower codend,
      17.53% in upper codend and 24.25%, mostly consisting of juveniles and sub-adults
      of finfishes and shellfishes, was excluded from upper codend. The mean CPUE
      registered for upper and lower codend were 7.23+/-1.04 SE and 5.84+/-0.96 SE kg
      h(-1) respectively. The CPUE of shrimps retained in upper and lower codends were
      significantly different (Kruskal-Wallis test (1,62), P<0.001), but the mean CPUE
      for fishes did not vary significantly. The average escapement of shrimps and
      juvenile fishes from upper codend were 0.06+/-0.02 SE kg h(-1) and 2.40+/-0.44 SE
      kg h(-1) respectively. Significant differences in the length composition between
      upper and lower codends were noticed for Megalaspis cordyla, Stolephorus waitei,
      Metapenaeus dobsoni and Parapenaeopsis stylifera. The experiments demonstrated in
      situ sorting ability of the device and its potential to reduce the bycatch of
      juveniles and sub-adults in shrimp trawls. 

PMID- 23875129
TI  - Characterisation of enterovirus 71 replication kinetics in human colorectal cell
      line, HT29.
AB  - Hand, Foot and Mouth Disease (HFMD), a contagious viral disease that commonly
      affects infants and children with blisters and flu like symptoms, is caused by a
      group of enteroviruses such as Enterovirus 71 (EV71) and coxsackievirus A16
      (CA16). However some HFMD caused by EV71 may further develop into severe
      neurological complications such as encephalitis and meningitis. The route of
      transmission was postulated that the virus transmit from one person to another
      through direct contact of vesicular fluid or droplet from the infected or via
      faecal-oral route. To this end, this study utilised a human colorectal
      adenocarcinoma cell line (HT29) with epithelioid morphology as an in vitro model
      for the investigation of EV71 replication kinetics. Using qPCR, viral RNA was
      first detected in HT29 cells as early as 12 h post infection (hpi) while viral
      protein was first detected at 48 hpi. A significant change in HT29 cells'
      morphology was also observed after 48 hpi. Furthermore HT29 cell viability also
      significantly decreased at 72 hpi. Together, data from this study demonstrated
      that co-culture of HT29 with EV71 is a useful in vitro model to study the
      pathogenesis of EV71. 

PMID- 23875131
TI  - A case of synchronous bilateral breast cancer with different pathological
      responses to neoadjuvant chemotherapy with different biological character.
AB  - We report a case of synchronous locally advanced bilateral breast cancer with
      different pathological responses to neoadjuvant chemotherapy with different
      biological character. The patient had presented bilateral breast cancer: the left
      breast cancer was hormone receptor negative, human epidermal growth factor
      receptor-2 (HER2) positive, and classified as T4bN1M0, stage IIIb, while the
      right was hormone receptor positive, HER2-negative, and classified as T4bN0M0,
      stage IIIb. We administered four cycles of anthracycline-based therapy followed
      by 12 weekly cycles of taxane with trastuzumab for neoadjuvant chemotherapy. We
      had achieved a significant left tumor reduction after each chemotherapy, but not
      right tumor. Bilateral modified radical mastectomies with axillary lymph-node
      dissection were performed. The therapeutic effect in the left was determined as a
      pathological complete response, in contrast to the right side. She has no
      recurrence for more than five years, though she had advanced cancer with
      oncologic emergency. This case could be an informative experience to understand
      the relation of tumor biology and response to systemic therapy. 

PMID- 23875132
TI  - Proteolytic enzymes from Bromelia antiacantha as tools for controlled tissue
      hydrolysis in entomology.
AB  - A crude extract with high proteolytic activity (78.1 EU/mL), prepared from ripe
      fruit of Bromelia antiacantha was used to hydrolyze and remove soft tissues from
      the epigyne of Apopyllus iheringi. This enzymatic extract presented four actives
      isoforms which have a broad substrate specificity action. Enzyme action on
      samples was optimized after evaluation under different conditions of pH, enzyme
      substrate ratio and time (parameters selected based on previous studies) of
      treatment (pH 4.0, 6.0 and 8.0 at 42 degrees C with different amount of enzyme).
      Scanning electron microscopy was used to evaluate conditions resulting in
      complete digestion of epigyne soft tissues. Optimal conditions for soft tissue
      removal were 15.6 total enzyme units, pH 6.0 for 18 h at 42 degrees C. 

PMID- 23875133
TI  - Arthroscopic suture anchor tenodesis: loop-suture technique.
AB  - With advancements in arthroscopic surgery, arthroscopic biceps tenodesis with
      suture anchor recently has been reported to be a reasonable option for the
      treatment of biceps pathologies, especially for those that are symptomatic or
      accompanied by a rotator cuff tear. We introduce our technique of arthroscopic
      biceps tenodesis with suture anchor that we call the loop-suture technique, which
      is constructed with 1 loop strand and another sutured strand. This technique can
      help to improve biceps grip and simultaneously minimize longitudinal splitting of
      the tendon. In addition, it is relatively simple and can be performed with the
      use of conventional devices and arthroscopic portals used for rotator cuff
      repair, without the formation of additional portals or a separate incision for
      the tenodesis. 

PMID- 23875134
TI  - All-Inside Posterior Cruciate Ligament Reconstruction With a GraftLink.
AB  - Posterior cruciate ligament (PCL) reconstructions are challenging surgeries.
      Recent advances have included double-bundle PCL, arthroscopic inlay, and all
      inside techniques. This technical note presents an anatomic, single-bundle, all
      inside PCL reconstruction with an anterior tibialis allograft GraftLink
      construct. The surgery was performed with FlipCutter guide pins and ACL TightRope
      RT. The case involved a 22-year-old woman with an isolated grade 3 PCL tear that
      had failed nonoperative treatment. The technique described is minimally invasive.

PMID- 23875135
TI  - Arthroscopic hybrid fixation of a tibial eminence fracture in children.
AB  - The treatment of an anterior cruciate ligament (ACL) avulsion fracture is
      controversial, especially in skeletally immature patients, because of concerns
      about physeal damage. To reduce the risk of physeal injury, an arthroscopic
      technique was performed. A bioabsorbable suture anchor was inserted through
      anteromedial portals and fixed to a bioabsorbable suture anchor at the center of
      the fracture bed; it was then passed through the threads at the ACL avulsion
      fragment and tied with the ACL substance. After this, the avulsion fragment was
      repaired by an all-inside technique between the distal portion of the ACL and the
      transverse ligament and periosteum by a suture hook. The arthroscopic hybrid
      technique using a suture anchor with an all-inside repair is more rigid and safe.
      In addition, this physeal-sparing fixation is possible in immature patients. 

PMID- 23875136
TI  - A novel technique for advancing the inferior labrum in a bankart repair.
AB  - Passing suture during a Bankart repair can be a difficult task. A key component
      of a Bankart repair involves shifting the anteroinferior capsule and labrum
      superiorly. This technical note describes a new technique of reaching the
      inferior aspect of the Bankart lesion from posterior. Typical suture passers push
      the tissue further away. Using a SutureLasso through the low posterolateral
      portal allows one to push the tissue from inferior toward the suture anchor,
      making it simpler to advance the capsulolabral complex. Three suture anchors are
      used in the anteroinferior quadrant. The lowest suture anchor is the critical
      anchor for advancing the capsule and labrum. The SutureLasso is placed into the
      axillary recess through the low posterolateral portal, and the nitinol wire is
      advanced through the capsule and labrum, retrieving the suture and pulling it
      back through the tissue for tying with a sliding locking knot. This ensures good
      superior advancement of the tissue and helps obtain an optimal arthroscopic
      result in Bankart repair. Additional anchors are placed, and suture passage for
      the middle and superior anchors is then completed from anterior. The advancement
      and restoration of the tissue tightness provide the optimal components for an
      excellent result. 

PMID- 23875137
TI  - Medial quadriceps tendon-femoral ligament: surgical anatomy and reconstruction
      technique to prevent patella instability.
AB  - Detailed anatomic dissections of the deep medial knee retinaculum have shown a
      consistent prominent anatomic structure extending from the distal deep quadriceps
      tendon to the adductor tubercle region, forming a distinct medial quadriceps
      tendon-femoral ligament (MQTFL). Reconstruction of this anatomic structure has
      yielded consistent medial stabilization of the patellofemoral joint without
      drilling into the patella over more than 3 years in patients with recurrent
      patella instability and dislocation. Results are similar to those of MPFL
      reconstruction but with reduced risk of patella fracture, a known and serious
      complication of MPFL reconstruction. The reconstruction graft is secured at the
      anatomic femoral origin of the MQTFL and brought under the vastus medialis such
      that it may be woven and attached to the deep distal medial quadriceps tendon to
      provide a secure, reliable reproduction of the MQTFL and excellent stabilization
      of the patellofemoral joint without risk of patella fracture. 

PMID- 23875139
TI  - Subcalcaneal bursitis with plantar fasciitis treated by arthroscopy.
AB  - We report the successful arthroscopic treatment of a case of subcalcaneal
      bursitis with plantar fasciitis. To our knowledge, this is the first report on
      arthroscopic excision of a subcalcaneal bursa. Right heel pain developed in a 50
      year-old woman, without any obvious cause. She reported that the heel pain
      occurred immediately after waking and that the heel ached when she walked.
      Magnetic resonance imaging showed an extra-articular, homogeneous, high-intensity
      lesion in the fat pad adjacent to the calcaneal tubercle on T2-weighted sagittal
      and coronal images and thickening of the plantar fascia on T2-weighted sagittal
      images. A diagnosis of a recalcitrant subcalcaneal bursitis with plantar
      fasciitis was made, and surgery was performed. The arthroscope was placed between
      the calcaneus and the plantar fascia. With the surgeon viewing from the lateral
      portal and working from the medial portal, the dorsal surface of the degenerative
      plantar fascia was debrided and the medial half of the plantar fascia was
      released, followed by debridement of the subcalcaneal bursal cavity through the
      incised plantar fascia. Full weight bearing and gait were allowed immediately
      after the operation. At the latest follow-up, the patient had achieved complete
      resolution of heel pain without a recurrence of the mass, confirmed by magnetic
      resonance imaging. 

PMID- 23875138
TI  - Improved visualization of the 70 degrees  arthroscope in the treatment of talar
      osteochondral defects.
AB  - Osteochondral defects (OCDs) of the talus are a common cause of residual pain
      after ankle injuries. When conservative treatment fails, arthroscopic debridement
      combined with drilling/microfracturing of the lesion (bone marrow stimulation
      [BMS] procedures) has been shown to provide good to excellent outcomes. Not
      uncommonly, talar OCDs involve the borders of the talar dome. These uncontained
      lesions are sometimes difficult to visualize with the 30 degrees  arthroscope,
      with potential negative effect on the clinical outcome of an arthroscopic BMS
      procedure. The use of the 70 degrees  arthroscope has been described for a
      multitude of common knee, shoulder, elbow, and hip procedures. The purpose of
      this article is to show the usefulness of the 70 degrees  arthroscope in
      arthroscopic BMS procedures, pointing out which kinds of talar OCDs can benefit
      most from its use. 

PMID- 23875140
TI  - Arthroscopy of the sternoclavicular joint.
AB  - Traditionally, an open approach has been required to undertake any surgical
      intervention for intra-articular sternoclavicular joint pathology. This in itself
      carries a certain operative morbidity, including damage to the underlying
      mediastinal structures and damage to the sternoclavicular and costoclavicular
      ligaments, with subsequent joint instability and unsightly scarring. This
      technical note describes an arthroscopic approach to the sternoclavicular joint
      that reduces this morbidity. The evolution of the technique including the
      rationale for portal placement and the angle of instrument insertion is
      explained. Experience of over 50 arthroscopic procedures including diagnostic
      arthroscopy, discectomy, excision of loose bodies, and washout and debridement
      after infection and excision of the medial end of the clavicle for osteoarthritis
      is detailed. 

PMID- 23875141
TI  - Intra-articular hip injection using anatomic surface landmarks.
AB  - Intra-articular hip injection is a frequently used technique for diagnostic and
      therapeutic purposes and is gaining more importance for the early diagnosis of
      hip disease. It is commonly performed with imaging guidance such as
      ultrasonographic or fluoroscopic control. We describe our technique of injection
      of the hip using relative distances from anatomic surface landmarks, with the
      needle insertion point at the site of the proximal anterolateral portal for hip
      arthroscopy, with a posterior direction of 30 degrees  and targeted toward a
      junctional point between 2 perpendicular lines, 1 distal from the anterior
      superior iliac spine and the second anterior from the tip of the greater
      trochanter. This technique can be used without imaging guidance in the outpatient
      clinic. Moreover, it minimizes the need for radiographic exposure for more
      critical injections, such as the injection of contrast material before conducting
      magnetic resonance arthrogaphy of the hip. 

PMID- 23875142
TI  - Medial patellofemoral ligament reconstruction using hamstring autograft in
      children and adolescents.
AB  - We introduce an anatomic reconstruction technique for the medial patellofemoral
      ligament using a free hamstring autograft in skeletally immature patients. We
      dock the 2 ends of the graft in the superior-medial patella using sockets and
      secure the femoral graft attachment in a socket tunnel distal to the physis. This
      technique minimizes the risk of injury to the growth plate and still enables
      accurate and successful anatomic positioning of the hamstring autograft. 

PMID- 23875143
TI  - Arthroscopic treatment of a reverse hill-sachs lesion.
AB  - Acute traumatic posterior shoulder instability is a rare injury. Such injuries
      can result in significant bone defects of the anterior humeral head that require
      surgical intervention. In the past, small to medium defects have been treated by
      a soft-tissue or bone transfer into the lesion. We present an arthroscopic
      technique for addressing these lesions in which the middle glenohumeral ligament
      is sutured into the defect, thereby making it an extra-articular defect and
      preventing it from engaging the posterior glenoid. 

PMID- 23875144
TI  - Arthroscopic and computer-assisted high tibial osteotomy using standard total
      knee arthroplasty navigation software.
AB  - Opening-wedge high tibial osteotomy is an increasingly performed procedure for
      treatment of varus gonarthrosis and correction of malalignment during meniscal
      transplantation or cartilage restoration. Precise preoperative planning and
      meticulous surgical technique are required to achieve an appropriate mechanical
      axis correction. We describe our technique of arthroscopic and computer-assisted
      high tibial osteotomy using commonly available total knee arthroplasty navigation
      software as an intraoperative goniometer. We believe that our technique, by
      providing intraoperative real-time guidance of the degree of correction that is
      accurate and reliable, represents a useful tool for the surgeon who uncommonly
      performs high tibial osteotomy. 

PMID- 23875145
TI  - The "anchor shape" technique for long head of the biceps tenotomy to avoid the
      popeye deformity.
AB  - Surgical options for symptomatic pathologies of the long head of the biceps (LHB)
      include tenotomy and tenodesis. Tenotomy is surgically simple and quick, does not
      require immobilization, and avoids implant complications. However, it is
      associated with residual "Popeye" muscle deformity and biceps muscle cramps.
      Tenodesis avoids Popeye deformity, but it is technically a more difficult
      operation with a longer rehabilitation period and possible implant complications.
      The purpose of this report is to describe a novel technique for LHB tenotomy that
      avoids the Popeye muscle deformity. Before releasing the LHB from its anchor over
      the superior labrum, this technique consists of making an oblique incision,
      involving 50% of the tendon, distal to its attachment at the superior labrum. A
      second standard complete tenotomy incision is made about 1.5 cm medial to the
      oblique incision. The remaining stump of the LHB at the tendon-labrum junction is
      resected. The first incision, an oblique incomplete incision, allows the remnant
      of the LHB to open up and form an "anchor shape" that anchors the LHB at the
      articular entrance of the bicipital groove, thus decreasing the risk of Popeye
      deformity. 

PMID- 23875146
TI  - All-inside arthroscopic meniscal repair with meniscal cinch.
AB  - The number of commercially available all-arthroscopic meniscal repair devices has
      increased in recent years. Although inside-out vertical mattress sutures have
      been considered the gold standard in the past, recent biomechanical studies have
      shown that some all-arthroscopic repair devices provide comparable strength. To
      successfully use these devices, surgeons must understand proper insertion
      technique. The purpose of this article is to demonstrate this technique for the
      Meniscal Cinch (Arthrex, Naples, FL). 

PMID- 23875147
TI  - Medial patellofemoral ligament reconstruction using a modified "reverse-loop"
      technique.
AB  - Medial patellofemoral ligament reconstruction is a commonly performed procedure
      for patellofemoral instability. In recent years the surgery has evolved
      considerably as the anatomy and goals of reconstruction have become more defined.
      This has resulted in numerous surgical options involving various fixation
      devices. Furthermore, as biomechanical data accumulate regarding the importance
      of graft position and tension, surgical techniques for applying this knowledge
      with precision are needed. This technical note with an accompanying video details
      one such technique that may be applied to various methods of fixation, allowing
      for improved precision and possibly resulting in a stronger fixation construct. 

PMID- 23875148
TI  - Arthroscopic transosseous-equivalent rotator cuff repair.
AB  - Rotator cuff repair techniques continue to evolve in an effort to improve repair
      biomechanics, maximize the biologic environment for tendon healing, and
      ultimately improve patient outcomes. The arthroscopic transosseous-equivalent
      technique was developed to replicate the favorable tendon-bone contact area for
      healing seen in open transosseous tunnel repair. In this technical note and
      accompanying video, we present our all-arthroscopic transosseous-equivalent
      rotator cuff repair technique with a focus on technical pearls. 

PMID- 23875149
TI  - Endoscopic compartment release for chronic exertional compartment syndrome.
AB  - Exertional compartment syndrome of the leg is a condition that can cause chronic
      debilitating pain in active persons during a variety of aerobic activities.
      Nonoperative treatments using stretching protocols and activity modifications are
      often unsuccessful, and thus several operative strategies have been used to treat
      this condition. A novel technique for endoscopically assisted fasciotomy for
      chronic exertional compartment syndrome is described. By use of a small laterally
      based incision and an arthroscope, polydioxanone sutures are passed
      percutaneously along the anterior and lateral compartments with the Spectrum
      suture-shuttling device (ConMed Linvatec, Largo, FL). These sutures are used to
      retract the skin and subcutaneous tissues over the respective compartments. This
      method allows excellent visualization of the intercompartmental septum, the
      superficial peroneal nerve, and all perforating vessels. The anterior and lateral
      compartments can be safely and completely released with this minimally invasive
      approach. The patient is allowed to return to full activity at 6 weeks
      postoperatively, because of the decreased soft-tissue disruption. 

PMID- 23875150
TI  - A simple surgical technique for subpectoral biceps tenodesis using a double
      loaded suture anchor.
AB  - Multiple different surgical techniques have previously been described to address
      long head of the biceps tendinopathy. Subpectoral biceps tenodesis has proven to
      be an effective procedure to relieve pain and maintain function. We describe a
      surgical technique for subpectoral biceps tenodesis using a single double-loaded
      suture anchor implant. Advantages of this procedure include the ease of implant
      placement and the freedom this technique affords to perform the anchor placement
      without direct visualization of the docking site. 

PMID- 23875151
TI  - Elbow arthroscopy: a new setup to avoid visual paradox and improve triangulation.
AB  - Elbow arthroscopy is a useful diagnostic and therapeutic tool for various
      conditions. Conventional arthroscopy with the patient in the prone or lateral
      position where the screen is placed on the opposite side makes it difficult to
      interpret the image, results in visual paradox, and is associated with difficult
      triangulation. We present a modified setup for the operating room to help
      eliminate these problems and improve triangulation. 

PMID- 23875152
TI  - Endoscopic repair of a gluteus medius tear at the musculotendinous junction.
AB  - Abductor tendon tears are an increasingly recognized clinical entity in patients
      with lateral thigh pain and weakness. These "rotator cuff tears of the hip"
      typically result from chronic, nontraumatic rupture of the anterior fibers of the
      gluteus medius. Although the abductor tendon typically tears from the osseous
      insertion, the case discussed here ruptured at the musculotendinous junction.
      This is the first report of this abductor tear subtype and its endoscopic repair.

PMID- 23875153
TI  - Arthroscopic hip labral repair.
AB  - Labral tears in the hip may cause painful clicking or locking of the hip, reduced
      range of motion, and disruption to sports and daily activities. The acetabular
      labrum aids stabilization of the hip joint, particularly during hip motion. The
      fibrocartilaginous structure extends the acetabular rim and provides a suction
      seal around the femoroacetabular interface. Treatment options for labral tears
      include debridement, repair, and reconstruction. Repair of the labrum has been
      shown to have better results than debridement. Labral refixation is achieved with
      sutures anchored into the acetabular rim. The acetabular rim is trimmed either to
      correct pincer impingement or to provide a bleeding bed to improve healing.
      Labral repair has shown excellent short-term to midterm outcomes and allows
      patients to return to activities and sports. Arthroscopic rim trimming and labral
      refixation comprise an effective treatment for labral tears with an underlying
      diagnosis of femoroacetabular impingement and are supported by the peer-reviewed
      literature. 

PMID- 23875154
TI  - Endoscopic repair of full-thickness gluteus medius tears.
AB  - Tears in the gluteus medius and minimus tendons recently have emerged as an
      important cause of chronic greater trochanteric pain syndrome. Increasing
      recognition of the gluteal insertion as a cause of chronic pain and weakness, as
      well as technologic advances in endoscopic hip surgery, has made gluteal
      insertional repair a rapidly emerging technique in minimally invasive surgery of
      the hip. We present an endoscopic double-row technique for gluteal insertional
      repair that allows for visualization, debridement, and repair, re-creating the
      normal footprint. 

PMID- 23875155
TI  - Outlet biceps tenodesis: a new technique for treatment of biceps long head tendon
      injury.
AB  - Degeneration and tearing of the long head of the biceps brachii tendon (LHBT) are
      common intra-articular findings, and surgical intervention including tenodesis or
      tenotomy is beneficial. A new arthroscopic shoulder technique may be performed
      through an anterior portal while one is viewing from a posterior portal: (1)
      Visualize the intra-articular biceps tendon. (2) Identify the segment of the LHBT
      to be enlarged. (3) Use a tissue modulation wand to enlarge the tendon. (4)
      Evaluate the diameter of the enlarged segment. It should be twice the original
      diameter. (5) Cut the biceps tendon at the proximal end of the enlarged segment.
      (6) View the tendon within the tunnel. (7) Identify and cut the remaining stump
      of the biceps tendon. Seventeen cadaveric shoulders were used to compare the
      pullout force, stiffness, and displacement of outlet tenodesis versus tenotomy.
      There was a significant increase in pullout force for the outlet tenodesis group
      when compared with tenotomy. This technique is used to operatively treat LHBT
      intra-articular pathology in patients who would benefit from tenotomy and
      traditional biceps tenodesis and may minimize the retraction of the biceps tendon
      distally. 

PMID- 23875156
TI  - Routine complete capsular closure during hip arthroscopy.
AB  - The utility of hip arthroscopy has recently progressed beyond diagnostic to
      therapeutic purposes addressing central and peripheral compartment pathologies.
      Capsulotomy provides freedom of visualization and instrumentation. The
      contribution to hip stability of both dynamic and static hip structures is not
      fully understood. However, both basic science biomechanical and clinical outcome
      studies have exhibited a relevant role of the capsule in hip stability. Though
      rare, iatrogenic post-arthroscopy subluxation and dislocation have been reported.
      Therefore many surgeons have cautioned against aggressive capsulotomy or
      capsulectomy without repair, because of the potential for precipitation of
      iatrogenic hip instability. We typically perform a "T" capsulotomy and recommend
      complete capsular closure in conjunction with labral repair and osseous femoral
      and acetabular treatment. A safe, efficient, and effective method to accomplish
      complete capsular closure is presented to reduce iatrogenic postoperative hip
      instability. 

PMID- 23875157
TI  - Long head of the biceps tenodesis with cortical button technique.
AB  - There are several options for long head of the biceps (LHB) tenodesis and yet no
      standard of care. This technical note describes a cortical button technique for
      LHB tenodesis. We have taken the BicepsButton (Arthrex, Naples, FL) for distal
      biceps acute primary repair and applied it to the LHB. The biceps tenotomy is
      completed arthroscopically, and a standard subpectoral approach is used. The
      biceps is pulled out and whipstitched starting at the myotendinous junction and
      moving proximally. The humerus is drilled in a unicortical manner slightly larger
      than the tendon, and the button is passed through a small hole to the posterior
      cortex. A suture through the tendon provides additional fixation strength to the
      construct. This is an elegant and effective method of tenodesis that uses a
      smaller-diameter drill hole in the humerus. The goals of LHB tenodesis are to
      restore function, reduce pain, and improve cosmesis. This technique offers
      comparable function and cosmesis with the potential advantage of improving
      postoperative pain outcomes and lowering the rate of complications. 

PMID- 23875158
TI  - Anatomic all-inside anterior cruciate ligament reconstruction using the
      translateral technique.
AB  - There is growing evidence that anatomic placement of the femoral tunnel in
      anterior cruciate ligament reconstruction confers biomechanical advantages over
      the traditional tunnel position. The anteromedial portal technique for anatomic
      anterior cruciate ligament reconstruction has many well-described technical
      challenges. This article describes the translateral all-inside technique, which
      produces anatomic femoral tunnel placement using direct measurement of the medial
      wall of the lateral femoral condyle and outside-in drilling. All work is carried
      out through the lateral portal with all viewing through the medial portal. Thus
      there is no need for an accessory medial portal or hyperflexion of the knee
      during femoral socket preparation. A single quadrupled hamstring graft is used
      with cortical fixation at both the femoral and tibial tunnels. 

PMID- 23875159
TI  - Stem cell maintenance in a different niche.
AB  - To overcome the difficulty of controlling stem cell fate and function in
      applications to regenerative medicine, a number of alternative approaches have
      been made. Recent reports demonstrate that a non-cellular niche modulating the
      biophysical microenvironment with chemical factors can support stem cell self
      renewal. In our previous studies, early establishment was executed to optimize
      biophysical factors and it was subsequently found that the microgeometry of the
      extracellular matrix made huge differences in stem cell behavior and phenotype.
      We review here a three-dimensional, non-cellular niche designed to support stem
      cell self-renewal. The characteristics of stem cells under the designed system
      are further discussed. 

PMID- 23875160
TI  - Update on the treatment of endometriosis.
AB  - Endometriosis is defined as the presence of functional endometrial tissue outside
      the uterus, causing diverse progressive symptoms such as infertility, pelvic
      pain, and dysmenorrhea. Although endometriosis has been described since the
      1800s, the mechanisms responsible for its pathogenesis and progression remain
      poorly understood. It is well established that endometriosis grows and regresses
      in an estrogen-dependent fashion and the disease can be effectively cured by
      definitive surgery. However, prolonged medical therapy may be needed in most of
      the cases since conservative surgery is usually performed especially in young
      women. This treatment modality is often associated with only partial relief
      and/or recurrence of the disease. In the present review, up-to-date findings on
      the treatment of endometriosis will be briefly summarized. The outcomes of
      surgery in patients with endometriosis will be reviewed in terms of pelvic pain
      relief as well as infertility treatment largely based on recent Cochrane reviews
      and clinical reports. The efficacy of newer drugs including aromatase inhibitor,
      anti-tumor necrosis factor-alpha, and dienogest will be also reviewed based on
      recent clinical studies. 

PMID- 23875161
TI  - Effect of genistein administration on the recovery of spermatogenesis in the
      busulfan-treated rat testis.
AB  - OBJECTIVE: Impairment of spermatogenesis has been identified as an inevitable
      side effect of cancer treatment. Although estrogen treatment stimulates
      spermatogenic recovery from the impaired spermatogenesis by suppressing the intra
      testicular testosterone (ITT) level, side effects of estrogen are still major
      impediments to its clinical application in humans. Soybeans are rich in
      genistein, which is a phytoestrogen that binds to estrogen receptors and has an
      estrogenic effect. We investigated the effects of genistein administration on ITT
      levels, testis weight, and recovery of spermatogenesis in rats treated with a
      chemotherapeutic agent, busulfan. METHODS: Busulfan was administered
      intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously
      into the back, or genistein was administered orally. RESULTS: The weight of the
      testes was significantly reduced by the treatment with busulfan. The testis
      weight was partially restored after busulfan treatment by additional treatment
      with either the GnRH agonist or genistein. Busulfan also induced atrophy of a
      high percentage of the seminiferous tubules, but this percentage was decreased by
      additional treatment with either the GnRH agonist or genistein. Treatment with
      genistein was effective at suppressing and maintaining ITT levels comparable to
      that in the GnRH agonist group. CONCLUSION: Genistein effectively suppressed ITT
      levels and stimulated the recovery of spermatogenesis in rats treated with a
      chemotherapeutic drug. This suggests that genistein may be a substitute for
      estrogens, for helping humans to recover fertility after cancer therapy without
      the risk of side effects.

PMID- 23875162
TI  - Peroxisome proliferator-activated receptor gamma agonist suppresses human
      telomerase reverse transcriptase expression and aromatase activity in eutopic
      endometrial stromal cells from endometriosis.
AB  - OBJECTIVE: To investigate the effect of peroxisome proliferator activated
      receptor gamma (PPARgamma) agonist on the cell proliferation properties and
      expression of human telomerase reverse transcriptase (hTERT) and aromatase in
      cultured endometrial stromal cell (ESC) from patients with endometriosis.
      METHODS: Human endometrial tissues were obtained from women with endometriosis
      and healthy women (controls) using endometrial biopsy. Isolated ESCs were
      cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]
      2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and
      cyclooxygenase (COX)-2 by western blotting according to the addition of
      rosiglitazone (PPARgamma agonist). RESULTS: We demonstrate that the cultured ESCs
      of endometriosis showed hTERT protein overexpression and increased cellular
      proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner.
      At the same time, PPARgamma agonist also inhibited aromatase and COX-2
      expression, resulting in decreased prostaglandin E2 production in the ESCs of
      endometriosis. CONCLUSION: This study suggests that PPARgamma agonist plays an
      inhibitory role in the proliferative properties of eutopic endometrium with
      endometriosis by down-regulation of hTERT and COX-2 expression; this could be a
      new treatment target for endometriosis.

PMID- 23875163
TI  - Blood glucose levels, insulin concentrations, and insulin resistance in healthy
      women and women with premenstrual syndrome: a comparative study.
AB  - OBJECTIVE: To compare the blood glucose levels, insulin concentrations, and
      insulin resistance during the two phases of the menstrual cycle between healthy
      women and patients with premenstrual syndrome (PMS). METHODS: From January of
      2011 to the August of 2012, a descriptive cross-sectional study was performed
      among students in the School of Medicine of Jahrom University of Medical
      Sciences. We included 30 students with the most severe symptoms of PMS and 30 age
      frequency-matched healthy controls. We analyzed the serum concentrations of
      glucose, insulin, and insulin resistance by using the glucose oxidase method,
      radioimmunometric assay, and homeostasis model assessment of insulin resistance
      equation, respectively. RESULTS: No significant differences between the
      demographic data of the control and PMS groups were observed. The mean
      concentrations of glucose of the two study groups were significantly different
      during the follicular and luteal phases (p=0.011 vs. p<0.0001, respectively). The
      amounts of homeostasis model assessment of insulin resistance of the two study
      groups were significantly different in the luteal phase (p=0.0005). CONCLUSION:
      The level of blood glucose and insulin resistance was lower during the two phases
      of the menstrual cycle of the PMS group than that of the controls.

PMID- 23875164
TI  - Cessation of gonadotropin-releasing hormone antagonist on triggering day in
      flexible multiple-dose protocol: A randomized controlled study.
AB  - OBJECTIVE: To investigate outcomes of stimulated IVF cycles in which GnRH
      antagonist was omitted on the ovulation triggering day. METHODS: A total of 86
      women who underwent controlled ovarian hyperstimulation with recombinant FSH and
      GnRH antagonist flexible multiple-dose protocols were recruited and prospectively
      randomized into the conventional group (group A) or cessation group (group B).
      The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading
      follicle reached 14 mm in diameter and was continuously administered until the
      hCG triggering day (group A, 43 cycles) or until the day before hCG
      administration (group B, 43 cycles). The maturity of oocytes, fertilization rate,
      embryo quality, and implantation and clinical pregnancy rates were evaluated.
      RESULTS: The duration of ovarian stimulation, total dose of gonadotropins, serum
      estradiol levels on hCG administration day, and number of oocytes retrieved were
      not significantly different between the two groups. The total dose of GnRH
      antagonist was significantly lower in group B than group A (2.5+/-0.9 vs. 3.2+/
      0.8 ampoules, p<0.05). There was no premature luteinization in any of the
      subjects. The proportion of mature oocytes and fertilization rate were not
      significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs.
      66.4%, respectively). There were no significant differences in the implantation
      or clinical pregnancy rates. CONCLUSION: Our prospective randomized study
      suggested that cessation of GnRH antagonist on the hCG administration day during
      a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist
      without compromising its effects on pregnancy rates.

PMID- 23875165
TI  - The effectiveness of earlier oocyte retrieval in the case of a premature
      luteinizing hormone surge on hCG day in in vitro fertilization-embryo transfer
      cycles.
AB  - OBJECTIVE: To evaluate the efficacy of earlier oocyte retrieval in IVF patients
      with a premature LH surge on hCG day. METHODS: One hundred forty IVF patients
      (164 cycles) with premature LH surge on hCG day were included, retrospectively.
      We divided them into 2 study groups: LH surge with timed ovum pick-up (OPU) 36
      hours after hCG injection (group B, 129 premature cycles), and LH surge with
      earlier OPU within 36 hours after hCG injection (group C, 35 cycles). Control
      groups were tubal factor infertility without premature LH surge (group A, 143
      cycles). RESULTS: The mean age (year) was statistically higher in group C than in
      groups A or B (38.2+/-5.4 vs. 36.2+/-4.2 vs. 36.8+/-4.9, respectively; p=0.012).
      The serum LH levels (mIU/mL) on hCG day were significantly higher in group B and
      C than in group A (22.7+/-14.9 vs. 30.3+/-15.9 vs. 3.2+/-2.9, respectively;
      p>0.001). Among groups A, B, and C, 4.9%, 31.7%, and 51.4% of the cycles,
      respectively, had no oocytes, and the overall rates of cycle cancellation (OPU
      cancellation, no oocyte, or no embryos transferrable) were 15.4%, 65.9%, and
      74.3%, respectively. The fertilization rate (%) was significantly higher in group
      B than in group C (73.2+/-38.9 vs. 47.8+/-42.9, p=0.024). The clinical pregnancy
      rate was significantly higher in group C than in groups A and B (44.4% vs. 27.3%
      vs. 9.1%, respectively, p=0.021). However, the miscarriage rate was also higher
      in group C than in group B (22% vs. 0%, respectively, p=0.026). CONCLUSION:
      Earlier OPU may not be effective in reducing the risk of cycle cancellation in
      patients with premature LH surge on hCG day. A larger scale study will be
      required to reveal the effectiveness of earlier ovum retrieval with premature LH
      surge.

PMID- 23875166
TI  - Association between serum anti-Mullerian hormone level and ovarian response to
      mild stimulation in normoovulatory women and anovulatory women with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To evaluate the correlation between serum levels of anti-Mullerian
      hormone (AMH) and ovarian response to mild stimulation in normoovulatory women
      and anovulatory women with polycystic ovary syndrome (PCOS). METHODS: Seventy
      four cycles of mild stimulation (clomiphene citrate+gonadotropin followed by
      timed intercourse or intrauterine insemination) performed in normoovulatory women
      (57 cycles) and anovulatory women with PCOS (17 cycles). Ovarian sensitivity was
      defined by the number of mature follicles (>=14 mm) on triggering day per 100 IU
      of gonadotropin. A correlation between ovarian sensitivity and the baseline serum
      AMH level (absolute or multiples of the median [MoM] value for each corresponding
      age) was calculated. Correlation between ovarian response and serum AMH level was
      evaluated. RESULTS: Ovarian sensitivity to mild stimulation was positively
      correlated with absolute serum AMH (r=0.535, p<0.001) or AMH-MoM value (r=0.390,
      p=0.003) in normoovulatory women, but this correlation was not observed in
      anovulatory women with PCOS (r=0.105, p>0.05, r=-0.265, p>0.05, respectively).
      CONCLUSION: Ovarian response to mild stimulation is possibly predicted by the
      serum AMH level in normoovulatory women, but not in anovulatory women with PCOS.

PMID- 23875167
TI  - Effects of insulin-sensitizing agents and insulin resistance in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of insulin
      sensitizing agents on hormonal and metabolic parameters as well as menstrual
      patterns in women with polycystic ovary syndrome (PCOS). METHODS: One hundred and
      twenty-three patients with PCOS were included. Metformin was administered to
      patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no
      improvement of the menstrual cycle or metformin-related adverse effects
      developed, the patients changed medication to a daily dose of either 15 mg
      pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or
      recovery of ovulation was evaluated. Hormonal and metabolic profiles were
      compared between the response and non-response group to insulin sensitizing
      agents. RESULTS: One hundred and five patients with PCOS were treated with
      metformin for 3 months. Forty-eight patients (45.7%) showed improvement of
      menstrual cycle regularity after 3 months of metformin use, whereas 57 patients
      (54.3%) had no change. The mean free testosterone measured after 3 months of
      treatment was significantly lower in metformin responders than in non-responders.
      The other parameters did not differ between the groups. Of the 23 patients who
      used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in
      their menstrual cycles. CONCLUSION: Metformin treatment seems to be effective for
      the improvement of menstrual cyclicity irrespective of insulin resistance in
      women with PCOS. When metformin related adverse effect occurred, pioglitazone
      would be effective for aiding the resumption of the menstrual cycle.

PMID- 23875168
TI  - Promoting physical activity in pediatric oncology. Where do we go from here?

PMID- 23875169
TI  - Targeting the AMP-Activated Protein Kinase for Cancer Prevention and Therapy.
AB  - Despite the advances in biomedical research and clinical applications, cancer
      remains a leading cause of death worldwide. Given the limitations of conventional
      chemotherapeutics, including serious toxicities and reduced quality of life for
      patients, the development of safe and efficacious alternatives with known
      mechanism of action is much needed. Prevention of cancer through dietary
      intervention may hold promise and has been investigated extensively in the recent
      years. AMP-activated protein kinase (AMPK) is an energy sensor that plays a key
      role in the regulation of protein and lipid metabolism in response to changes in
      fuel availability. When activated, AMPK promotes energy-producing catabolic
      pathways while inhibiting anabolic pathways, such as cell growth and
      proliferation - thereby antagonizing carcinogenesis. Other anti-cancer effects of
      AMPK may include promoting autophagy and DNA repair upon UVB damage. In the last
      decade, interest in AMPK has grown extensively as it emerged as an attractive
      target molecule for cancer prevention and treatment. Among the latest
      developments is the activation of AMPK by naturally occurring dietary
      constituents and plant products - termed phytochemicals. Owing to their efficacy
      and safety, phytochemicals are considered as an alternative to the conventional
      harmful chemotherapy. The rising popularity of using phytochemicals for cancer
      prevention and therapy is supported by a substantial progress in identifying the
      molecular pathways involved, including AMPK. In this article, we review the
      recent progress in this budding field that suggests AMPK as a new molecular
      target in the prevention and treatment of cancer by phytochemicals. 

PMID- 23875170
TI  - Radioimmunotherapy of B-Cell Non-Hodgkin's Lymphoma.
AB  - This manuscript reviews current advances in the use of radioimmunotherapy (RIT)
      for the treatment of B-cell non-Hodgkin's lymphoma (NHL). RIT has been in use for
      more than 20 years and has progressed significantly with the discovery of new
      molecular targets, the development of new stable chelates, the humanization of
      monoclonal antibodies (MAbs), and the use of pretargeting techniques. Today, two
      products targeting the CD20 antigen are approved: (131)I-tositumomab
      (Bexxar((r))), and (90)Y-ibritumomab tiuxetan (Zevalin((r))). (131)I-tositumomab
      is available in the United States, and (90)Y-ibritumumab tiuxetan in Europe, the
      United States, Asia, and Africa. RIT can be integrated in clinical practice using
      non-ablative activities for treatment of patients with relapsed or refractory
      follicular lymphoma (FL) or as consolidation after induction chemotherapy in
      front-line treatment in FL patients. Despite the lack of phase III studies to
      clearly define the efficacy of RIT in the management of B lymphoma in the era of
      rituximab-based therapy, RIT efficacy in NHL has been demonstrated. In relapsing
      refractory FL and transformed NHL, RIT as a monotherapy induces around 30%
      complete response with a possibility of durable remissions. RIT consolidation
      after induction therapy significantly improves the quality of the response. Dose
      limiting toxicity of RIT is hematological, depending on bone marrow involvement
      and prior treatment. Non-hematological toxicity is generally low. Different
      studies have been published assessing innovative protocols of RIT or new
      indications, in particular treatment in patients with aggressive lymphomas. High
      dose treatment, RIT as consolidation after different therapeutic induction
      modalities, RIT in first-line treatment or fractionated RIT showed promising
      results. New MAbs, in particular humanized MAbs, or combinations of naked and
      radiolabeled MAbs, also appear promising. Personalized dosimetry protocols should
      be developed to determine injected activity. 

PMID- 23875172
TI  - Molecular Characteristics in MRI-Classified Group 1 Glioblastoma Multiforme.
AB  - Glioblastoma multiforme (GBM) is a clinically and pathologically heterogeneous
      brain tumor. Previous studies of transcriptional profiling have revealed
      biologically relevant GBM subtypes associated with specific mutations and
      dysregulated pathways. Here, we applied a modified proteome to uncover abnormal
      protein expression profile in a MRI-classified group I GBM (GBM1), which has a
      spatial relationship with one of the adult neural stem cell niches,
      subventricular zone (SVZ). Most importantly, we identified molecular
      characteristics in this type of GBM that include up-regulation of metabolic
      enzymes, ribosomal proteins, and heat shock proteins. As GBM1 often recurs at
      great distances from the initial lesion, the rewiring of metabolism, and
      ribosomal biogenesis may facilitate cancer cells' growth and survival during
      tumor progression. The intimate contact between GBM1 and the SVZ raises the
      possibility that tumor cells in GBM1 may be most related to SVZ cells. In support
      of this notion, we found that markers representing SVZ cells are highly expressed
      in GBM1. Emerged findings from our study provide a specific protein expression
      profile in GBM1 and offer better prediction or therapeutic implication for this
      multifocal GBM. 

PMID- 23875173
TI  - MelanomaDB: A Web Tool for Integrative Analysis of Melanoma Genomic Information
      to Identify Disease-Associated Molecular Pathways.
AB  - Despite on-going research, metastatic melanoma survival rates remain low and
      treatment options are limited. Researchers can now access a rapidly growing
      amount of molecular and clinical information about melanoma. This information is
      becoming difficult to assemble and interpret due to its dispersed nature, yet as
      it grows it becomes increasingly valuable for understanding melanoma. Integration
      of this information into a comprehensive resource to aid rational experimental
      design and patient stratification is needed. As an initial step in this
      direction, we have assembled a web-accessible melanoma database, MelanomaDB,
      which incorporates clinical and molecular data from publically available sources,
      which will be regularly updated as new information becomes available. This
      database allows complex links to be drawn between many different aspects of
      melanoma biology: genetic changes (e.g., mutations) in individual melanomas
      revealed by DNA sequencing, associations between gene expression and patient
      survival, data concerning drug targets, biomarkers, druggability, and clinical
      trials, as well as our own statistical analysis of relationships between
      molecular pathways and clinical parameters that have been produced using these
      data sets. The database is freely available at
      http://genesetdb.auckland.ac.nz/melanomadb/about.html. A subset of the
      information in the database can also be accessed through a freely available web
      application in the Illumina genomic cloud computing platform BaseSpace at
      http://www.biomatters.com/apps/melanoma-profiler-for-research. The MelanomaDB
      database illustrates dysregulation of specific signaling pathways across 310
      exome-sequenced melanomas and in individual tumors and identifies the
      distribution of somatic variants in melanoma. We suggest that MelanomaDB can
      provide a context in which to interpret the tumor molecular profiles of
      individual melanoma patients relative to biological information and available
      drug therapies. 

PMID- 23875174
TI  - Identification of Pre- and Post-Treatment Markers, Clinical, and Laboratory
      Parameters Associated with Outcome in Renal Cancer Patients Treated with MVA-5T4.
AB  - The recent approvals of immunotherapeutic agents (Sipuleucel-T and Ipilimumab)
      for the treatment of different solid tumors gave a boost to the growing cancer
      immunotherapy field, even though few immunotherapy studies have demonstrated
      convincingly that there is a direct link between the predicted mode of action of
      an immunological compound and therapeutic benefit. MVA-5T4 (TroVax((r))) is a
      novel vaccine combining the tumor-associated antigen 5T4 to an engineered vector
      modified vaccinia Ankara (MVA). MVA helps to express the oncofetal 5T4 antigen
      and subsequently trigger a tumor-directed immune reaction. The safety and
      clinical benefit reported in multiple phase I and II clinical trials using MVA
      5T4 were encouraging; immune responses were induced in almost all treated
      patients, and associations between 5T4-specific cellular or humoral responses and
      clinical benefit were reported in most of the nine phase II trials. In
      particular, clinical studies conducted in renal cell carcinoma (RCC) patients
      have demonstrated an association between 5T4-specific (but not MVA) antibody
      responses and enhanced survival. This review describes the clinical studies using
      MVA-5T4 conducted in RCC that convincingly demonstrated that an antigen-specific
      immune response induced by vaccination is associated with enhanced patient
      survival and is not simply a function of the general "health" of patients. We
      will also provide our expert opinions on possible future better-designed clinical
      trials based on relevant biomarkers. In addition, various combinations of MVA-5T4
      and different and newer immunomodulator agents with promising clinical benefit
      will be discussed. 

PMID- 23875171
TI  - COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs.
AB  - Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory
      drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors, reduce the
      risk of developing cancer. Experimental studies in human cancer cell lines and
      rodent models of carcinogenesis support these observations by providing strong
      evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in
      tumorigenesis and its overexpression in various cancer tissues suggest that
      inhibition of COX-2 is responsible for the chemopreventive efficacy of these
      agents. However, the precise mechanisms by which NSAIDs exert their
      antiproliferative effects are still a matter of debate. Numerous other studies
      have shown that NSAIDs can act through COX-independent mechanisms. This review
      provides a detailed description of the major COX-independent molecular targets of
      NSAIDs and discusses how these targets may be involved in their anticancer
      effects. Toxicities resulting from COX inhibition and the suppression of
      prostaglandin synthesis preclude the long-term use of NSAIDs for cancer
      chemoprevention. Furthermore, chemopreventive efficacy is incomplete and
      treatment often leads to the development of resistance. Identification of
      alternative NSAID targets and elucidation of the biochemical processes by which
      they inhibit tumor growth could lead to the development of safer and more
      efficacious drugs for cancer chemoprevention. 

PMID- 23875175
TI  - Did we get pasteur, warburg, and crabtree on a right note?

PMID- 23875176
TI  - Endogenous tick viruses and modulation of tick-borne pathogen growth.
AB  - Ticks transmit a wide range of viral, bacterial and protozoan pathogens, many of
      which can establish persistent infections of lifelong duration in the vector tick
      and in some cases are transmitted transovarially to the next generation. In
      addition many ixodid and argasid tick cell lines and, by inference the parent
      ticks from which they were derived, harbor endogenous viruses (ETV) of which
      almost nothing is known. In general, low level persistent infections with viral
      pathogens (arboviruses) are not known to have a deleterious effect on tick
      survival and fitness, suggesting that they can strike a balance with the tick
      innate immune response. This tolerance of arbovirus infection may be modulated by
      the permanent presence of ETV in the host cell. In mosquito cells, temporary or
      permanent silencing of the genes of an endogenous virus by RNA interference can
      result in changes in replication rate of a co-infecting arbovirus. We propose
      that tick cell lines offer a useful model system for in vitro investigation of
      the modulatory effect of ETV on superinfecting pathogen survival and replication
      in ticks, using the molecular manipulation techniques applied to insect cells. 

PMID- 23875178
TI  - Ecology, biology and distribution of spotted-fever tick vectors in Brazil.
AB  - Spotted-fever-caused Rickettsia rickettsii infection is in Brazil the major tick
      borne zoonotic disease. Recently, a second and milder human rickettsiosis caused
      by an agent genetically related to R. parkeri was discovered in the country
      (Atlantic rainforest strain). Both diseases clearly have an ecological background
      linked to a few tick species and their environment. Capybaras (Hydrochoerus
      hydrochaeris) and Amblyomma cajennense ticks in urban and rural areas close to
      water sources are the main and long-known epidemiological feature behind R.
      rickettsii-caused spotted-fever. Unfortunately, this ecological background seems
      to be increasing in the country and disease spreading may be foreseen.
      Metropolitan area of Sao Paulo, the most populous of the country, is embedded in
      Atlantic rainforest that harbors another important R. rickettsii vector, the tick
      Amblyomma aureolatum. Thus, at the city-forest interface, dogs carry infected
      ticks to human dwellings and human infection occurs. A role for R. rickettsii
      vectoring to humans of a third tick species, Rhipicephalus sanguineus in Brazil,
      has not been proven; however, there is circumstantial evidence for that. A R.
      parkeri-like strain was found in A. ovale ticks from Atlantic rainforest and was
      shown to be responsible for a milder febrile human disease. Rickettsia-infected
      A. ovale ticks are known to be spread over large areas along the Atlantic coast
      of the country, and diagnosis of human infection is increasing with awareness and
      proper diagnostic tools. In this review, ecological features of the tick species
      mentioned, and that are important for Rickettsia transmission to humans, are
      updated and discussed. Specific knowledge gaps in the epidemiology of such
      diseases are highlighted to guide forthcoming research. 

PMID- 23875180
TI  - Laplace Beltrami Filter on QuadEdge Meshes.
AB  - This document describes a contribution to the Insight Toolkit intended to support
      the process of statistical analysis in Computational Anatomy. The methods
      included here operate on open or closed triagulated surfaces (represented by a
      QuadEdgeMesh). The filter assigns basis function values as Point Data on each
      vertex of the Mesh. This paper is accompanied with the source code, input data,
      parameters and output data that we used for validating the algorithm described in
      this paper. This adheres to the fundamental principle that scientific
      publications must facilitate reproducibility of the reported results.

PMID- 23875179
TI  - The Effects of Children on the Process of Recovery in Oxford Houses.
AB  - The effects of children on the process of substance use recovery for adults
      living in Oxford Houses is explored in two qualitative studies. Oxford Houses are
      self-run, community-based residential homes for small groups of adults who live
      together and support each other's efforts to recover from drug and/or alcohol
      addiction. In the first study, telephone interviews were conducted with 29 adults
      who were living in Oxford Houses that allowed children to live in the house with
      their parent. Results suggest that having children in the house supported a
      positive living environment for the recovery of house members. In the second
      study, telephone interviews were conducted with an additional 15 mothers who
      lived in Oxford Houses. These interviews focused on the effects of the mothers'
      addiction and recovery on their relationships with their children. This study
      found that most parents acknowledged the negative effects of their addiction on
      their relationship with their child and the effects of their recovery on
      improving those relationships.

PMID- 23875177
TI  - Interaction of the tick immune system with transmitted pathogens.
AB  - Ticks are hematophagous arachnids transmitting a wide variety of pathogens
      including viruses, bacteria, and protozoans to their vertebrate hosts. The tick
      vector competence has to be intimately linked to the ability of transmitted
      pathogens to evade tick defense mechanisms encountered on their route through the
      tick body comprising midgut, hemolymph, salivary glands or ovaries. Tick innate
      immunity is, like in other invertebrates, based on an orchestrated action of
      humoral and cellular immune responses. The direct antimicrobial defense in ticks
      is accomplished by a variety of small molecules such as defensins, lysozymes or
      by tick-specific antimicrobial compounds such as microplusin/hebraein or 5.3-kDa
      family proteins. Phagocytosis of the invading microbes by tick hemocytes is
      likely mediated by the primordial complement-like system composed of thioester
      containing proteins, fibrinogen-related lectins and convertase-like factors.
      Moreover, an important role in survival of the ingested microbes seems to be
      played by host proteins and redox balance maintenance in the tick midgut. Here,
      we summarize recent knowledge about the major components of tick immune system
      and focus on their interaction with the relevant tick-transmitted pathogens,
      represented by spirochetes (Borrelia), rickettsiae (Anaplasma), and protozoans
      (Babesia). Availability of the tick genomic database and feasibility of
      functional genomics based on RNA interference greatly contribute to the
      understanding of molecular and cellular interplay at the tick-pathogen interface
      and may provide new targets for blocking the transmission of tick pathogens. 

PMID- 23875182
TI  - Colorimetric sensing strategy for mercury(II) and melamine utilizing cysteamine
      modified gold nanoparticles.
AB  - A quantitative colorimetric sensing strategy utilizing cysteamine modified gold
      nanoparticles (CA-AuNPs) as reporters for Hg(2+) and melamine was demonstrated.
      Cysteamine is a cheap and commercially available aminothiol and is also the most
      important chelating ligand in coordination chemistry possessing the ability to
      coordinate to Hg(2+) and melamine. The terminal thiol group in cysteamine is used
      to bind to AuNPs and another terminal amine group is used as a colorimetric probe
      either for Hg(2+) or melamine. By adjusting the pH, protonation of cysteamine's
      terminal amine groups allows for tuning of the surface charge on the cysteamine
      modified gold nanoparticles. At acidic pH, the CA-AuNPs are positively charged
      due to the protonated amine groups, which may electrostatically bind melamine
      resulting in aggregation of CA-AuNPs, while at alkaline pH, the amine groups are
      deprotonated, and if Hg(2+) is present, they may form an N-Hg(2+)-N structure to
      induce the aggregation of CA-AuNPs. The detection limits (S/N = 3) of Hg(2+) and
      melamine were 30 nM and 80 nM respectively, which were comparable with or even
      lower than those of other single analyte methods. The proposed sensing
      mechanisms, which are based on electrostatic attraction for melamine and the N
      Hg(2+)-N structure for Hg(2+), were validated by zeta potential measurements. The
      facile one-step surface modification strategy for AuNPs is suitable for the
      effective analysis of large numbers of samples, which would open new
      opportunities for development of miniaturized Hg(2+) and melamine sensors. 

PMID- 23875183
TI  - Sulfonyl hydrazine-functionalized polymer as a specific capturer of reducing
      glycans from complex samples for high-throughput analysis by electrospray
      ionization mass spectrometry.
AB  - Qualitative and quantitative studies of glycosylation patterns of various
      biologically important proteins represent a key field for the understanding of
      their complex structure-function relationships. However, the analysis of
      glycoprotein glycans is usually undermined by tedious sample processing steps
      prior to detection, including deproteination, desalting and removal of some other
      non-glycan impurities, which results in considerable sample loss and increased
      difficulty of quantitative analysis. Herein we report a facile and versatile
      method for the quantitative isolation of reducing glycans from complex samples
      using sulfonyl hydrazine-functionalized polystyrene (SHPS) beads, namely the SHPS
      based glycan capturing procedure. This method allows the chemoselective and
      efficient condensation of the aldehyde group of reducing glycans with the active
      sulfonyl hydrazine group of SHPS beads under anhydrous conditions, resulting in
      the formation of sulfonyl hydrazone conjugates. The non-glycan components in
      samples, such as proteins, salts and some other impurities, can be completely
      removed by washing the sulfonyl hydrazone conjugates. Regeneration of the
      reducing glycans can be performed via mild hydrolysis of the washed sulfonyl
      hydrazone conjugates. This procedure is compatible with almost all the current
      techniques for the derivatization or detection of reducing glycans. We have
      obtained essential data for this method, including optimized reaction conditions,
      linearity and reproducibility for glycan quantitation, as well as a final glycan
      recovery ratio. Moreover, mass spectrometric analysis of the glycans from some
      complex biological samples, including milk, human blood plasma and fetal bovine
      serum, was achieved, demonstrating good applicability of this novel procedure. 

PMID- 23875181
TI  - Group interprofessional chronic pain management in the primary care setting: a
      pilot study of feasibility and effectiveness in a family health team in Ontario.
AB  - BACKGROUND: Approximately 18.9% of Canadians live with chronic pain. Primary care
      reform in Ontario presents unique opportunities to assess approaches to help
      these patients. OBJECTIVE: To assess the feasibility of an interprofessional
      primary care-based program for patients living with chronic pain, and to examine
      the potential impact of such a program on quality of life and health resource
      utilization. METHODS: An embedded mixed-methods evaluation (randomized controlled
      trial with waiting list control and semistructured interviews) of an eight-week
      series of small group sessions exploring multifactoral aspects of pain management
      was performed. Participants were randomly assigned to early intervention (EI) or
      delayed intervention (DI) groups. All participants received the intervention; the
      DI group served as a control group for comparison with the EI group. Outcomes
      included the Short Form-36 Health Survey version 2 (SF-36v2), medication use and
      health care utilization. Qualitative interviews were conducted to identify areas
      for program improvement. RESULTS: A total of 240 patients were recruited and 63
      agreed to participate. The mean (+/- SD) age of the participants was 55+/-14.1
      years and 62.3% were female. There was no significant difference in the mean
      change in SF-36v2 summary scores between the EI and DI groups. However, the SF
      36v2 subscale score for bodily pain was significantly improved in the EI group
      compared with the DI group after six months of observation (mean difference =
      13.1 points; P<0.05). There was also significant improvement in this score when
      both groups were pooled and aggregate preintervention and postintervention scores
      were compared. There was a significant decrease in the mean number of clinic
      visits in the six-month period following the intervention compared with the six
      month period before the intervention (P=0.043). CONCLUSION: An interprofessional
      program in primary care for patients living with chronic pain may lead to
      improvements in quality of life and health resource utilization. The challenges
      to the feasibility of the program and its evaluation are recruitment and
      retention of patients, leading to the conclusion that the program, as it was
      conducted in the present study, is not appropriate for this setting.

PMID- 23875184
TI  - Exclusive fluoride ion recognition and fluorescence "turn-on" response with a
      label-free DMN Schiff base.
AB  - A label-free DMN Schiff base (4) has been explored as a highly selective and
      sensitive fluoride ion receptor. Fluoride-induced deprotonation results in a
      charge transfer (CT) transition red shifted with a fluorescence 'turn-on'. Anion
      selectivity can be tuned by the electron push-pull property of substituents at
      the phenyl para-position. Selectivity for F(-) is attributed to the suitable
      acidity of -NH2. 

PMID- 23875185
TI  - Multicolour probes for sequence-specific DNA detection based on graphene oxide.
AB  - The bifunctionality of graphene oxide (GO) which can highly adsorb single
      stranded DNA (ssDNA) and effectively quench the emission of organic dyes is
      reasonably utilized in a multiplexed DNA detection system, achieving sensitive
      and selective detection of HIV, VV and EV, respectively. 

PMID- 23875186
TI  - A magnetic double-shell microsphere as a highly efficient reusable catalyst for
      catalytic applications.
AB  - A novel magnetic double-shell Fe3O4@TiO2/Au@Pd@TiO2 microsphere composed of a
      Fe3O4 core and double TiO2 shells with Au and Pd nanoparticles encapsulated is
      created. The microsphere can be used as a highly efficient reusable catalyst with
      superior catalytic activity and stability and magnetic separable capability in
      reduction of 4-nitrophenol.

PMID- 23875187
TI  - Response.

PMID- 23875188
TI  - Response.

PMID- 23875189
TI  - Response.

PMID- 23875190
TI  - Response.

PMID- 23875191
TI  - Growing pain: striving for quality, relevance and applicability in Cochrane
      Reviews.

PMID- 23875192
TI  - What should the Cochrane Collaboration do about research that is, or might be,
      fraudulent?

PMID- 23875193
TI  - Abstracts of the 5th Annual Meeting of the North American NeuroEndocrine Tumor
      Society. October 11-13, 2012. San Diego, California, USA.

PMID- 23875194
TI  - The long-term marriage between autoimmunity and internal medicine. Festschrift
      dedicated to Dr. Manuel Carlos Dias.

PMID- 23875195
TI  - Clinical and fundamental aspects of monocyte, macrophage and dendritic cell
      plasticity. Proceedings of the 25th Annual Meeting of the European Macrophage and
      Dendritic Cell Society (EMDS). September 22-24, 2011.

PMID- 23875196
TI  - A vision for the world. Interview of Dr Thomas Sze-Tong Chan with student
      reporters.

PMID- 23875197
TI  - Response to Barglow letter.

PMID- 23875198
TI  - Mountains' majesty. Replacement facility capitalizes on idyllic setting.

PMID- 23875199
TI  - [Contrast substances-induced nephropathy].
AB  - The increasing number of invasive procedures done with contrast agents makes the
      prevention of their induced nephropathy more urgent. At present, different
      methods are being developed to prevent contrast-induced nephropathy (CIN) with
      antioxidants, intrarenal vasodilators, hydration therapy, by accurately
      determining the amount of excreted fluid obtained from a urinary catheter and
      less toxic iodine-containing contrast agents are being put into practice.
      Unfortunately, the current guidelines for the prevention of CIN are inadequately
      followed in both Russia and foreign countries. This review covers the main
      components of the pathogenesis and risk factors of this pathology and its
      possible preventive measures.

PMID- 23875200
TI  - [Phosphate binders in chronic kidney disease: the positions of sevelamer].
AB  - The paper shows the role of phosphate binders in the correction of phosphorus and
      calcium metabolic disturbances in chronic kidney disease. The results of clinical
      trials demonstrating the efficacy and safety of sevelamer are discussed.

PMID- 23875201
TI  - [Hyperuricemia and the problem of chronic kidney disease].
AB  - The paper reviews the literature on the role of hyperuricemia as a risk factor
      for chronic kidney disease and as one of the factors for the progression of
      existing kidney disease. It gives epidemiological information on a relationship
      between hyperuricemia and kidney lesion. The mechanisms for the damaging action
      of uric acid on kidney tissue, which have experimentally and clinically observed,
      are considered. The main areas of hyperuricemia correction and its place in the
      total nephroprotection strategy are defined.

PMID- 23875202
TI  - [New data on parasite fauna of the Chinese sleeper Perccottus glenii
      (Actinopterygii: Odontobutidae) in Primorsky Territory with the description of a
      new myxozoan species from the genus Myxidium (Myxozoa: Myxidiidae)].
AB  - Examination of 116 individuals of Perccottus glenii from water bodies of
      Primorsky Territory of Russia (the Khanka Lake basin and the Peter the Great Bay
      basin) revealed the presence of 35 species/taxa of parasites. We give a
      description of a new species, Myxidium shedkoae sp. nov. Spherical plasmodoa of
      M. shedkoa sp. nov. are located in the gall bladder; spores are fusiform, with
      protrusive, pointed, or truncated-cone-shaped poles. The length of spores
      constitutes 12.6-14.9 (13.4) microm; width, 7.1-8.6 (7.9) microm; shell valves
      possess 8-10 ridges forming "papillary" pattern. Drawings and descriptions of
      parasites species poorly studied and recorded from Russia for the first time are
      given together with drawings and descriptions of some parasites determined only
      as genera: Triangula perccotti, Gyrodactylus sp., Phyllodistomum sp.,
      Paracoenogonimus ussuriensis (metacercaria), Cyathocotylidae gen. sp.
      (metacercaria) and Spiroxys japonicus (third-stage juvenile). Parasite fauna of
      P. glenii in Primorsky Territory comprises 66% of species/forms known for P.
      glenii in the native part of its range.

PMID- 23875203
TI  - [Peculiarities of the distribution of Cryptosporidia (Coccidia:
      Cryptosporydiidae) in monkeys in an apery].
AB  - A total of 520 monkeys belonging to 6 species (Macaca mullata, M. fascicularis,
      M. nemestrina, Cercopithecus aethiops, Papio anubis, and P. hamadrias) were
      investigated. Total frequency of occurrence of the protozoan Cryptosporidium in
      the Adler apery constituted 13.8%. The majority of parasites were found in
      animals with intestinal disorders such as diarrhea. The lowest frequency of
      cryptosporidias occurrence was revealed in clinically healthy monkeys. Among sick
      monkeys, the invasion was most common in infants under one year of age.
      Cryptosporidiosis is rarely found just as it is, and, as a rule, it accompanied
      by other parasitogenic and bacterial infections.

PMID- 23875204
TI  - Know thyself. Learning to better recognize highs and lows may help prevent blood
      glucose extremes.

PMID- 23875205
TI  - Story time. Your guide to diabetes in 12 works of fiction.

PMID- 23875206
TI  - Career counseling. You're ready to be all that you can be. But can you do it with
      diabetes?

PMID- 23875207
TI  - Making insulin. A behind-the-scenes look (and why you can't do it yourself at
      home).

PMID- 23875208
TI  - Kidney-friendly recipes.

PMID- 23875209
TI  - How sleep apnea affects the heart.  Poor-quality sleep and heart disease are
      connected.

PMID- 23875210
TI  - Can you die of a broken heart? For some, the stress of grief causes serious heart
      problems.

PMID- 23875211
TI  - Some heart attacks go unrecognized. Yet "symptomless" does not mean "harmless".

PMID- 23875212
TI  - Risk factors for peripheral artery disease pinpointed.

PMID- 23875213
TI  - Aspirin may prevent blood clots in the legs from recurring.

PMID- 23875214
TI  - Asessment of infants with respiratory distress.

PMID- 23875215
TI  - [Re: analysis of perinatal mortality in newborn infants with a birth weight of
      less than 1000 grams in Hospital San Cecilio in Granada (Spain) over the 1991
      2010 period].

PMID- 23875216
TI  - [Author reply--analysis of perinatal mortality in newborn infants with a birth
      weight of less than 1000 grams in Hospital San Cecilio in Granada (Spain) over
      the 1991-2010 period].

PMID- 23875217
TI  - "Immotile-cilia" syndrome and ciliary abnormalities induced by infection and
      injury.

PMID- 23875218
TI  - [Re: Sudden infant death. Wanted: not the culprits, but the ones who will be
      responsible for prevention].

PMID- 23875219
TI  - [Author reply to Dr. Manuel Rocca Rivarola].

PMID- 23875220
TI  - [Re: medication error in an extremely low birth weight infant: paracetamol
      overdose].

PMID- 23875221
TI  - [Author reply].

PMID- 23875222
TI  - [Re: I wish to congratulate Dr. Norma E. Rossato, author of the article on sudden
      infant death - wanted: not the culprits, but the ones who will be responsible for
      prevention].

PMID- 23875223
TI  - [Re: a school-based survey of recurrent non-specific low-back pain prevalence and
      consequences in children].

PMID- 23875224
TI  - Self-inflicted bilateral orchidectomy precipitated by erotic bizarre delusions: a
      case report.

PMID- 23875225
TI  - [Cloramphenicol treatment in nine children with bacillary dysentery].

PMID- 23875226
TI  - Response to the comment published in ATLA, on the declaration on openness on
      animal research.

PMID- 23875227
TI  - And now the selling of Obamacare. Will Americans buy a plan they don't love?

PMID- 23875228
TI  - Fear the burn. Why U.S. sunscreens are overshadowed.

PMID- 23875229
TI  - Critical shortage. As technology improves, the transplant list gets longer--but
      there aren't enough organs to go around.
AB  - While improving medical technology is making transplants more successful and more
      people eligible, it's also contributing to a problem. There is a growing crowd of
      people waiting for organ transplants, and they vastly outnumber potential donors
      each year. "It's a zero-sum game," says Dr. J. Michael Millis, left, medical
      director of transplantation services at University of Chicago Medicine. "We don't
      have enough organs."

PMID- 23875230
TI  - Pairing up. Early adopters of big data seek advisers, partners.

PMID- 23875231
TI  - High-tech precautions. FDA calls for controls against cyberattacks.

PMID- 23875232
TI  - Admissions conundrum. CMS looks to reduce long observation stays, but hospitals
      see it as another cut.

PMID- 23875233
TI  - 'The cost will drop'. Myriad Genetics' shares drop as competitors enter.

PMID- 23875234
TI  - The 'July effect' challenge. ACGME effort aims to improve doc trainees' skills.

PMID- 23875235
TI  - Culture conscious. Leaders talk quality, change needed for improvement at Virtual
      Conference.

PMID- 23875236
TI  - PET coverage extended. Medicare won't stop covering post-treatment scans.

PMID- 23875237
TI  - Fears balloon over reform. But benefits of healthcare overhaul likely to gain
      momentum.

PMID- 23875238
TI  - Steps toward transparency. Health organizations need to be open with consumers
      about pricing.

PMID- 23875239
TI  - Shifting burdens. Hospitals increasingly concerned over effects of cost-sharing
      provisions in health plans to be offered through insurance exchanges.

PMID- 23875240
TI  - Numbers game. Supply of skilled coders key to ICD-10 transition.

PMID- 23875241
TI  - Largest revenue-cycle management firms. Ranked by total number of healthcare
      revenue-cycle contracts, 2012.

PMID- 23875242
TI  - The role of miR-145 in microvasculature.
AB  - Increasing evidence suggests that microRNAs(miRs) play a crucial role in the
      cardiovascular system, and recent studies have revealed a significant role of
      miRs in vascular biology and disease, miR-145 is one of the most-studied miRs,
      and especially in the vascular smooth muscle cell (VSMCs) proliferation,
      differentiation, and phenotypic switching. In cardiovascular system, miR-145 is
      not only important for heart and vascular development but also plays an essential
      role in cardiac pathological factors, such as hypertrophy, and ischemia. However,
      its potential role in microvasculature has not been systematically evaluated yet.
      We are just beginning to understand the regulation of miR in vascular biology. In
      particular, the miR biogenesis and regulatory pathways in the vascular system
      have not yet been well characterized, This review focuses on the basic biology
      and mechanism of action of miR-145 specifically pertaining to microvascular
      development, pericyte and disease, In addition it addresses the potential for miR
      145 to be used therapeutically in the treatment of microvascular disease.

PMID- 23875243
TI  - Synthesis of telmisartan impurity B.
AB  - Telmisartan is an antihypertensive drug and is a specific angiotensin II receptor
      (AT1) antagonist. According to European Pharmacopoeia 7 Edition 2008 telmisartan
      quality standard, there are seven impurities in telmisartan. Impurity B which is
      not available commercially and no synthetic method is published so far. We report
      herein the first synthesis of impurity B. The structure of impurity B was
      confirmed by 1H NMR, 13C NMR and MS data. These findings should be important for
      quality control purposes in the manufacture and quality control of telmisartan.

PMID- 23875244
TI  - Development of a simple LC-MS/MS method for the determination of febuxostat in
      human plasma and its application to a bioequivalence study.
AB  - The purpose of this study was to design a simple, sensitive and rapid liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for a febuxostat
      bioequivalence study in healthy Chinese male volunteers. In this method,
      febuxostat and etodolac (internal standard) were isolated from plasma samples by
      protein precipitation with acetonitrile. The supernatant was chromatographed on a
      Zorbax SB-C18 (150 x 3.0 mm, 3.5-microm particle size, Agilent) column with a
      SecurityGuard Inertsil Symmetry C18 column (12.5 x 4.6 mm, 5-microm particle
      size, Waters). The lower limit of quantification for febuxostat in 0.2 mL of
      human plasma was 13.40 ng x mL(-1), and the linearity was achieved over a
      concentration range from 13.40 to 21440 ng x mL(-1). Febuxostat tablets from
      Hengrui Medicine Co., Ltd (test, Jiangsu, China) and from Takeda pharmaceuticals
      america, Inc. (reference, Deerfield, IL) were evaluated following a single 80 mg
      oral dose to 18 healthy volunteers. Bioequivalence was determined by calculating
      90% confidence intervals (90% CI) for the ratio of C(max), AUC(0-t), and AUC(0
      infinity) values for the test and reference products, using logarithmic
      transformed data. The calculated 90% CIs for the ratio of C(max) (88.7-131.2%),
      AUC(0-t) (99.2-122.7%) and AUC(0-infinity) (99.5-123.1%) values for the test and
      reference products were all located within the bioequivalence criteria range (80
      125% for AUC, and 70-143% for Ca(mzax)), proposed by State of Food and Drug
      Administration [SFDA, 2005. China]. It was concluded that the two febuxostat
      formulations (test and reference) analyzed were bioequivalent in terms of rate
      and extent of absorption and the method met the principle of quick and easy
      clinical analysis.

PMID- 23875245
TI  - Preparation, characterization and in vitro release study of gallic acid loaded
      silica nanoparticles for controlled release.
AB  - Gallic acid (GA) is an interesting pharmaceutical component of plants. However,
      the short lifetime and the autoxidation of GA in aqueous solution significantly
      reduces its bioavailability and the residence time in the body system. In this
      study, GA was chemically bound to silica nanoparticles to control the release of
      GA based on the hydrolysis of the chemical bonds, and a silica nanoparticle drug
      delivery system was established. Gallic acid loaded silica nanoparticles (GA
      SiO2) were synthesized by a modified Stober method. The Fourier Transform
      Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD) analysis proved that GA
      did conjugate to silica nanoparticles. The particle size of the GA-SiO2
      nanoparticles observed by Scanning Electron Microscope (SEM) was about 30 nm and
      the drug loading efficiency determined by Thermo Gravimetric
      Analysis/Differential Scanning Calorimetry (TGA/DSC) was 89.39%. The in vitro
      release study demonstrated that GA could be gradually released from the GA-SiO2.
      In addition, the antioxidant capability increased continuously during the
      immersion time, so the GA could serve as an excellent antioxidant to scavenge 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radicals in a long release period. Therefore,
      this study provided a novel drug delivery system for GA with controlled release
      capability and prolonged antioxidant activity.

PMID- 23875246
TI  - Characterization of in vitro biotransformation of the new oral anticoagulants,
      the factor VIIa inhibitors AS1927819-00 and AS1932804-00.
AB  - We recently developed a prodrug (AS1932804-00, CMP) of the novel FVIIa inhibitor
      AS1924269-00, which possesses a carbamate amidine backbone. In addition, we
      developed another type of prodrug (AS1927819-00, OXP) with an oxime amidine
      backbone. In this study, we investigated the efficiency of conversion of these
      novel FVIIa prodrugs to their active forms by evaluating the production of the
      active form in vitro by using microsomes, mitochondria, and cryopreserved
      hepatocytes, and compared it with the in vivo conversion mechanisms of the
      prodrugs (oxime amidine vs. carbamate amidine). We observed that OXP and CMP
      showed improved oral absorption, and the efficiency of conversion of CMP to the
      active form was higher than that of OXP. The in vivo rate of conversion of OXP to
      its active form was low in rats, and compared to liver microsomes and
      mitochondria, cryopreserved hepatocytes supplemented with serum and coenzymes
      were an appropriate metabolic test tool. On the other hand, the efficiency of
      conversion of CMP to its active from could be appropriately evaluated using small
      intestinal microsomes. The development of a prodrug can be optimized when
      information about the stability of carboxylic acid esters in the presence of
      serum esterases, membrane permeability of intermediate forms, and differential
      tissue specificity to metabolic activities for carbamate and oxime backbones of
      amidine can be obtained.

PMID- 23875247
TI  - Metabolism of fenofibrate in beagle dogs: new metabolites identified and
      metabolic pathways revealed.
AB  - Fenofibrate is a prototypical agonist of peroxisome proliferator-activated
      receptor alpha (PPARalpha) which is well known to be associated with species
      related carcinogenesis. Important species differences have been reported in its
      metabolism and elimination pattern. Its new metabolites have been revealed in
      Cynomolgus monkeys and Sprague-Dawley rats. However in beagle dogs, several polar
      metabolites of fenofibrate have not been identified yet. In this study, beagle
      dogs were orally dosed with fenofibrate mixed with feeds. Urine and plasma
      samples were collected and subject to LC-MS/MS by comparison with authentic
      compounds and confirmed using an API 4000 Q-TRAP system. In vitro cultured
      primary hepatocytes were used to reveal metabolic pathways and confirm the data
      in vivo. Seven new metabolites of fenofibrate in dogs were identified, and their
      metabolic pathways were revealed. Fenofibrate in beagle dogs was found to be more
      prone to be metabolized into other secondary metabolites than fenofibric acid,
      compared with that in rats.

PMID- 23875248
TI  - A clinical study on insomnia in patients with cancer during chemotherapy
      containing high-dose glucocorticoids.
AB  - In this prospective, open-labeled study, 240 cancer patients were assigned to
      either a high-dose glucocorticoids (HDG) group that received chemotherapy
      containing HDG, or a control group that received chemotherapy without
      glucocorticoids. The Pittsburgh Sleep Quality Index (PSQI) was chosen to assess
      insomnia. The results of the study showed that dimensions of sleep latency, sleep
      duration, and sleep efficiency had the three largest differences in values and
      numbers of patients, with a score increase in the HDG group compared to the
      control group (p < 0.001). After chemotherapy in the HDG group, the PSQI score
      significantly increased in patients with stage II cancer (both p < 0.05), and
      patients diagnosed with lymphoma (p < 0.01), whereas the complete response and
      partial response rates (p < 0.05) had the smallest elevations. The average score
      of each dimension did not significantly decrease after hypnotics (p > 0.05). Our
      study suggests that the major clinical manifestations of insomnia in cancer
      patients receiving chemotherapy containing HDG include difficulty falling asleep,
      short sleep duration, and low sleep efficiency. however, we cannot definitively
      state that hypnotics can improve poor sleep quality.

PMID- 23875249
TI  - Effect of beta-aescin extract from Chinese buckeye seed on chronic venous
      insufficiency.
AB  - The aim of this study was to explore the mechanism of domestic beta-aescin
      treating chronic venous insufficiency through observing its actions on the
      isolated canine saphenous venous tension, venous pressure, venous return and
      lymphatic return. The isolated canine spiral saphenous venous tension test was
      performed to detect the activity of the beta-aescin. Furthermore, in the
      condition of constant canine femoral artery perfusion kept in the extracorporeal
      circulation, we measured the changes of the canine femoral artery pressure,
      femoral artery flow and the lymphatic return flow after intravenous injection of
      the agent. The results showed that when beta-aescin was administrated at the dose
      between 5.0 x 10(-5)-5.25 x 10(-4) mol/L, it increased obviously the contractile
      tension of the venous to norepinephrine in a dose-dependent manner. With canine
      femoral artery perfusion kept constant, beta-aescin, whose doses were 50 mg and
      100 mg, reinforced intently the canine femoral venous tension accelerated the
      rise of the venous pressure. These finding suggested that domestic betabeta
      aescin extracted from Chinese Buckeye Seed had an effect on chronic venous
      insufficiency by strengthening the venous tension, increasing the venous pressure
      and promoting venous return and lymphatic return.

PMID- 23875250
TI  - Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by
      regulating the expression of IkappaBalpha, c-Jun and androgen receptor.
AB  - Curcumin possesses chemopreventive properties against several types of cancer,
      but the molecular mechanisms by which it induces apoptosis of cancer cells and
      inhibits cancer cell proliferation are not clearly understood. To evaluate the
      antitumor activity of curcumin for prostate cancer, we used an androgen dependent
      LNCaP prostate cancer cell line and an androgen independent PC-3 prostate cancer
      cell line as experimental models. We treated these cells with curcumin and then
      evaluated the effects of curcumin on cell cycle profiling and apoptosis, as well
      as the activation of NF-kaapaB and c-jun in these cells. The results showed that
      the ratios of apoptosis in LNCaP and PC-3 cells were significantly elevated in a
      dose dependent manner after exposure to curcumin. In addition, curcumin induces
      the G2/M cell cycle arrest of LNCaP and PC-3 cells in a dose dependent manner.
      Mechanistically, we found that curcumin upregulated the protein level of NF
      kappaB inhibitor IkappaBalpha and downregulated protein levels of c-Jun and AR.
      These data suggest that curcumin is a promising agent for the treatment of both
      androgen-dependent and androgen-independent prostate cancer.

PMID- 23875251
TI  - Nifedipine inhibits angiotensin II-induced cardiac fibrosis via downregulating
      Nox4-derived ROS generation and suppressing ERK1/2, JNK signaling pathways.
AB  - Nifedipine, a classic L-type dihydropyridine calcium channel blocker (CCB), has
      been reported to possess multiple cardioprotective properties. However, little is
      known about the effects of nifedipine on cardiac fibrosis induced by
      angiotensinII (AngII) and the detailed molecular mechanisms. In this study, we
      found that nifedipine attenuated AngII-induced cardiac fibrosis in vitro via
      inhibiting the proliferation, differentiation of cardiac fibroblasts and
      antagonizing the upregulation of extracellular matrix (ECM) protein fibronectin
      (FN) and the pro-fibrotic cytokine connective tissue growth factor (CTGF).
      Furthermore, nifedipine suppressed the upregulation of NAD(P)H oxidase 4 (Nox4)
      and the production of reactive oxygen species (ROS) induced by AngII. In
      addition, it markedly inhibited the phosphorylation of extracellular signal
      regulate kinases 1/2 (ERK1/2) and c-Jun NH(2)-terminal kinase (JNK) stimulated by
      AngII. However, nifedipine exhibited no effect on the variation of intracellular
      Ca2+ concentration ([Ca2+]i). These results suggested that (1) nifedipine
      inhibited cardiac fibrosis induced by AngII; (2) the anti-fibrotic effects of
      nifedipine may be mediated by interfering with the production of ROS and the
      activation of ERK1/2 and JNK signaling pathways; (3) the classic calcium channel
      blocking action of nifedipine may not be involved in the anti-fibrotic
      activities.

PMID- 23875252
TI  - Vitamin K4 induces tumor cytotoxicity in human prostate carcinoma PC-3 cells via
      the mitochondria-related apoptotic pathway.
AB  - Vitamin K4 (VK4) is a synthetic hydrophilic menadione compound, which is
      clinically used as hemostasis medicine. It has been reported that several vitamin
      Ks had inhibitory effects on various cancer cells. However, there is no report
      about VK4s anticancer activity. The goal of this study was to investigate the
      inhibitory effect of VK4 on human prostate PC-3 cells and the mechanisms
      involved. We found that VK4 dose-dependently inhibited cell proliferation in PC-3
      cells with an IC50 value of about 20.94 microM. Hoechst 33258 Staining results
      showed that VK4 caused DNA fragmentation in PC-3 cells. PI staining results
      indicated that VK4-induced PC-3 cell cycle arrest at the S phase. Further
      mechanistic studies revealed that VK4-mediated induction of apoptosis in PC-3
      cell is associated with disruption of mitochondrial membrane potential, down
      regulation of Bcl-2, and up-regulation of Bax, release of cytochrome c from
      mitochondria, and activation of caspase-3 and PARR Thus, VK4 might be useful in
      prostate cancer chemotherapy.

PMID- 23875253
TI  - Acitretin exhibits inhibitory effects towards UDP-glucuronosyltransferase
      (UGT)1A9-mediated 4-methylumbelliferone (4-MU) and propofol glucuronidation
      reaction.
AB  - The present study aimed to evaluate the potential risk of drug-drug interactions
      associated with acitretin which is a drug for therapy of psoriasis approved by
      the Food and Drug Administration (FDA). The initial screening of acitretin's
      inhibition towards 4-methylumbelliferone (4-MU) glucuronidation catalyzed by
      important UDP-glucuronosyltransferase (UGT) isoforms in the liver showed that
      UGT1A9 activity was strongly inhibited by acitretin with other UGT isoforms
      negligibly influenced. The inhibition type is best fit to competitive inhibition,
      and the inhibition kinetic parameter (K(i)) was determined to be 3.5 microM. The
      inhibition behaviour of acitretin towards UGT1A9 activity did not exhibit probe
      substrate-dependent behaviour when selecting human liver microsomes (HLMs)
      catalyzed propofol-O-glucuronidation as probe reaction of UGT1A9. The same
      inhibition type and similar inhibition parameters (K(i) = 3.2 microM) were
      obtained. Using the maximum plasma exposure dose of acitretin (C(max)), the
      C(max)/K(i) values were calculated to be 0.23 and 0.25 when selecting 4-MU and
      propofol as probe substrates, respectively. All these results indicate a
      potential clinical drug-drug interaction between acitretin and 4-MU or propofol.

PMID- 23875254
TI  - Kaempferide-7-O-(4"-O-acetylrhamnosyl)-3-O-rutinoside reduces myocardial
      infarction size after coronary artery ligation in rats.
AB  - Kaempferide-7-O-(4"-O-acetylrhamnosyl)-3-O-rutinoside (A-F-B) is a novel
      flavonoid extracted from the leaves of Actinidia kolomikta. We recently reported
      that A-F-B administration could improve lipid profiles. A-F-B actions are
      associated with regulating the activities of PAP and HMG-CoA reductase in hepatic
      tissue. This study evaluated the effects of A-F-B on acute myocardial infarction
      (AMI) in rats. An AMI model was established by ligating the left anterior
      descending coronary artery. The myocardial infarct size (MIS), creatine kinase
      (CK-MB) activity, troponin T level, endothelial nitric oxide synthase (eNOS)
      activity, superoxide dismutase (SOD) activity, catalase activity, malondialdehyde
      (MDA) content, nitric oxide (NO) content were measured. The results showed that
      the groups treated with A-F-B showed a dose-dependent reduction in MIS. A-F-B
      markedly inhibited the elevation of the activity of CK-MB, troponin T level, and
      the content of MDA induced by AMI. A-F-B also showed a capacity to increase the
      activities of SOD, catalase, and eNOS. The NO content in A-F-B-treated groups
      also augmented. The findings suggest that A-F-B exerted cardioprotective effects
      against acute myocardial ischemic injury by regulating antioxidative enzymes
      activity and endothelial nitric oxide synthase activity.

PMID- 23875256
TI  - [One hundred years of surgery under the patronage of the Swiss Society of
      Surgery].

PMID- 23875255
TI  - Development and validation of a risk score for predicting invasive fungal
      infectious in an intensive care unit.
AB  - Delay in the initiation of appropriate antifungal therapy is associated with
      substantial morbidity and mortality. The aim of this study was to derive a risk
      score system for the development of invasive fungal infections in an intensive
      care unit (ICU). We retrospectively evaluated 1812 patients who stayed in the ICU
      for > or = 4 days, used univariate and multivariable logistic regression to
      identify potential risk factors associated with invasive fungal infections (IFI),
      and created a risk score system. Seven variables were identified as important
      predictors of ICU-IFI (diabetes mellitus, gastrointestinal surgery, hematological
      malignancies, mechanical ventilation > or = 2 days, central venous catheter,
      total parenteral nutrition, broad-spectrum antibiotic use > or = 4 days). The
      area under the receiver operating characteristic curve was 0.807 and was similar
      in the validation set. The percentages of patients with ICU-IFI in the low,
      intermediate, and high risk groups were 5.2%, 31.6%, and 63.2% in the derivation
      cohort and 4.2%, 30.1%, and 66.7% in the validation cohort, respectively. A new
      risk score was developed to predict ICU-IFI and was validated in an independent
      cohort. The new risk score may help clinicians identify patients who are at high
      risk of developing ICU-IFI and increase their odds of survival.

PMID- 23875257
TI  - [Management of early rectal cancer: total mesorectal excision versus transanal
      resection?].
AB  - Management of rectal cancer is changing, due to better screening programs. An
      increased number of early rectal cancers are found, for which a radical surgery
      is not necessary in every cases. The development of new transanal resection
      techniques by minimally invasive surgery or robotics, allows to offer the patient
      less invasive technique with a better quality of life and sometimes preventing
      the creation of a stoma. This article summarizes the current situation in the
      field of transanal resection for early rectal cancer and the results in terms of
      oncologic and surgical outcomes. An appropriate selection of the patients is
      necessary to define who can benefit the most from these techniques.

PMID- 23875258
TI  - [Popliteal artery aneurysms: management in 2013].
AB  - Although rare, popliteal artery aneurysms are the most common peripheral
      aneurysms and are frequently associated with abdominal aorta aneurysms. They are
      often bilateral. One third of patients are asymptomatic at diagnosis, with an
      insidious evolution. Symptomatic patients may present with symptoms of either
      acute ischemia or chronic ischemia, or rarely compression or rupture. Surgical
      exclusion of aneurysm followed by venous bypass remains the treatment of choice.
      Endovascular treatment is an attractive alternative currently reserved for
      patients at high risk, with good anatomical criteria. Elective treatment before
      symptoms onset is preferable given the best results in terms of patency and
      complications. A conservative approach is allowed for small aneurysms without
      major embolic risk provided careful monitoring by ultrasound.

PMID- 23875259
TI  - [Management of the carotid artery stenosis].
AB  - In the western world, the carotid-artery stenosis is one of the major causes of
      ischemic stroke in elderly people. The principal therapeutic indication is a
      symptomatic stenosis > 50% in the first two weeks and the surgical approach has
      shown the best results. Despite inferior results to carotid endarterectomy in
      terms of post-operative rate of stroke and/or death, except for young patients,
      carotid stenting remains the best choice in patients at high surgical risk. The
      best medical treatment, consisting in correction of cardiovascular risk factors,
      statin therapy and anti-aggregation led to a drastic reduction in the annual rate
      of stroke associated to carotid stenosis and thus limited the surgical
      intervention in asymptomatic patient to men with a life expectancy of at least 5
      years and a stenosis > 70%.

PMID- 23875260
TI  - [Management of pectus excavatum].
AB  - Management of pectus excavatum Congenital chest wall deformities are considered
      to be anomalies in chest wall growth related to excessive or insufficient growth
      (aplasia or dysplasia) of the osseous or cartilaginous structures or the rib
      cage. These deformities are associated in 95% to overgrowth leading into
      depression (pectus excavatum) or protuberance of the sternum (pectus carinatum).
      Pectus excavatum may lead to cardiopulmonary disorder or impact on patient's self
      esteem. The management of pectus excavatum has evolved this last decade with
      minimal invasive repair.

PMID- 23875261
TI  - [Robotic general surgery: where do we stand in 2013?].
AB  - While the number of publications concerning robotic surgery is increasing, the
      level of evidence remains to be improved. The safety of robotic approach has been
      largely demonstrated, even for complex procedures. Yet, the objective advantages
      of this technology are still lacking in several fields, notably in comparison to
      laparoscopy. On the other hand, the development of robotic surgery is on its way,
      as the enthusiasm of the public and the surgical community can testify. Still,
      clear clinical indications remain to be determined in the field of general
      surgery. The study aim is to review the current literature on robotic general
      surgery and to give the reader an overview in 2013.

PMID- 23875262
TI  - [Medical technology innovation: why get involved and how?].
AB  - Medical technologies are an intrinsic part of our daily practice. More than a
      simple recipient of novel medical devices, clinicians have a unique role to play
      in medtech innovation. They are invaluable assets for testing devices and guiding
      manufacturers towards the most clinically relevant solutions. More importantly,
      they have a direct view on patient needs and can therefore identify unmet
      clinical needs. As these skills are not part of medical school curricula, new
      centers in medtech innovation education are arising across Europe following the
      success of US programs. These centers offer a full curriculum in medtech
      innovation so that doctors can more actively participate and foster innovation in
      their field. This new knowledge can allow us to initiate our own innovations and
      potentially influence the future of our own practice.

PMID- 23875264
TI  - [Ambiguous promises of human "neuromodulation"].

PMID- 23875263
TI  - [Shortage of physicians in the canton of Fribourg. Crossing general practitioners
      in Canton with medical students of Fribourg].

PMID- 23875265
TI  - [Doctor, you don't know it all!].

PMID- 23875266
TI  - [HIV: reservoirs in infected patients].

PMID- 23875267
TI  - [What the Furosemide Teva situation did not tell us].

PMID- 23875268
TI  - [Twenty years of Bertrand Kiefer].

PMID- 23875269
TI  - Medical, dental, data protection?

PMID- 23875271
TI  - Future of medicine. Payment reform needed to rein in healthcare spending.

PMID- 23875270
TI  - Good, not-so-good changes face doctors, patients today.

PMID- 23875272
TI  - ICD-10: can physician groups stave off or delay implementation? As some
      physicians fight the mandate, payers and EHR vendors get ready.

PMID- 23875273
TI  - Monitoring the beat of ancillary services in cardiac care. Some services can work
      in tandem with those of cardiologists to heir improve patient care.

PMID- 23875274
TI  - Telemedicine: patient demand, cost containment drive growth. Joining the trend
      may not be as expensive or time-consuming as you think, experts say.

PMID- 23875275
TI  - Is a risk retention group right for your medical malpractice insurance needs?

PMID- 23875276
TI  - Document carefully in a group practice to avoid raising red flags for auditors.

PMID- 23875277
TI  - Simple steps can protect, expand primary care capacity.

PMID- 23875278
TI  - Plato versus hippocrates.

PMID- 23875279
TI  - The obesity epidemic. While America swallows $147 billion in obesity-related
      healthcare costs, physicians called on to confront the crisis.

PMID- 23875280
TI  - Patient engagement remains cornerstone of primary care's future.

PMID- 23875281
TI  - How the ACA is reshaping medicine. Improvements in compensation, payer
      collaboration offset by provider shortages, incentive uncertainty.

PMID- 23875282
TI  - Private payers re-examining reimbursement. A host of new payment models will
      bring pressure on PCPs to hold down costs, improve quality.

PMID- 23875283
TI  - 7 legal issues to consider before an independent contractor departs.

PMID- 23875284
TI  - POS billing changes effective April 1.

PMID- 23875285
TI  - Examine the pros and cons of a buyout offer.

PMID- 23875286
TI  - Consider alternatives to adding provider.

PMID- 23875287
TI  - Florida medical home may offer a model for the future of senior healthcare.

PMID- 23875288
TI  - Online monitoring of N2O emissions from a partial nitritation (SHARON) reactor.

PMID- 23875289
TI  - Studying stress response profiles with high throughput microarrays: a case study
      in Daphnia exposed to different cyanobacterial stressors.

PMID- 23875290
TI  - High-resolution time-of-flight mass spectrometry for suspect screening and target
      quantification of pharmaceuticals in river water.
AB  - The growing interest in screening and quantification of potential harmful
      pharmaceuticals in the environment requests multi-residue analytical techniques.
      Large-volume injection ultra performance liquid chromatography (LVI-UPLC) in
      combination with full-spectrum high-resolution mass spectrometry (HRMS) is a
      promising alternative for the state-of-the-art MS/MS instruments, because of its
      ability to analyse a virtually unlimited number of analytes thereby avoiding the
      time-consuming sample enrichment steps. We developed and fully validated an
      innovative analytical method for suspect screening and target quantification of a
      set of 69 pharmaceutical compounds in surface water based on LVI-UPLC coupled to
      a quadrupole time-of-flight (QTOF) MS. In a systematic research, we showed that
      optimal mass accuracy was obtained after centroiding the spectra. A novel suspect
      screening strategy was developed, assuring the detection of 95% of the
      pharmaceuticals spiked in surface water by modelling the variability of the
      signal intensity-dependent accurate mass error. A first screening of five Belgian
      river water samples revealed the occurrence of 30 pharmaceuticals (antibiotics,
      analgesics, antidepressants, alkylating agents, antiinflammatories, etc.).
      Concentrations between 17 ng/L up to 3.3 microg/L were subsequently measured by
      the validated target quantification.

PMID- 23875291
TI  - The combined effects of DOC and salinity on the accumulation and toxicity of
      copper in mussel larvae.

PMID- 23875292
TI  - Impact of cadmium and zinc on root system of Lolium perenne and Trifolium repens.

PMID- 23875293
TI  - Selective uptake of microplastics by a marine bivalve (Mytilus edulis).

PMID- 23875294
TI  - Evaluation of the biofilm forming capacity of the 2, 6-dichlorobenzamide (BAM)
      degrading Aminobacter sp. strain MSH1 at macropollutant and micropollutant BAM
      concentrations.

PMID- 23875295
TI  - Functional screening of a metagenomic library from algal biofilms.

PMID- 23875296
TI  - Study of the force induced dissociation of molecular bonds.

PMID- 23875297
TI  - Development of a test to assess the banana bunchy top virus transmissibility
      through direct analyze of its aphid vector Pentalonia nigronervosa.

PMID- 23875298
TI  - A kernel-based model to predict interaction between methanotrophic and
      heterotrophic bacteria.

PMID- 23875299
TI  - Methane emission mitigation by methane-oxidizing bacteria immobilized on building
      materials.

PMID- 23875300
TI  - Dietary fiber affects intestinal mucosal barrier function by regulating
      intestinal bacteria in weaning piglets.

PMID- 23875301
TI  - Can prenatal nutritional constraints in the chicken embryo have long-term effects
      on the post-hatch performance and glucose metabolism?

PMID- 23875302
TI  - Investigation of the relationship between the quality of fresh pork and sound
      levels, starting from unloading the pigs till slaughtering.

PMID- 23875303
TI  - Immobilization of beta-galactosidase on membranes for process intensification.

PMID- 23875304
TI  - Development of an experimental device allowing plant - plant interaction studies
      and in situ dynamic trapping of volatile organic compounds emitted by barley
      (Hordeum distichon L.) roots.

PMID- 23875305
TI  - Application of biobased materials for packing short and medium shelf life food
      products.

PMID- 23875307
TI  - On-line flow cytometry profiling of Escherichia coli stress response.

PMID- 23875306
TI  - Models that ignore oil droplet uptake are sufficiently accurate to predict the
      bioaccumulation of oil-associated PAHs.

PMID- 23875308
TI  - Potential of the spherical densiometer to estimate light availability in
      temperate broad-leaved forests.

PMID- 23875309
TI  - Long-term measurements of volatile organic compounds exchanges above a maize
      field at Lonzee (Belgium).

PMID- 23875310
TI  - Bacterial and odor profile of polyester and cotton clothes after a fitness
      session.

PMID- 23875311
TI  - Diatom silica-titania materials for photocatalytic air purification.

PMID- 23875312
TI  - (Bio)synthesis, extraction and purification of garlic derivatives showing
      therapeutic properties.

PMID- 23875313
TI  - In vitro characterization of gastrointestinal behavior of Butyricicoccus
      pullicaecorum, a novel butyrate producing isolate with probiotic potential to
      counterbalance dysbiosis in inflammatory bowel disease.

PMID- 23875314
TI  - Influence of microalgae strain-specific parameters in hydrothermal liquefaction
      of microalgae for biofuels production.

PMID- 23875315
TI  - Integration of wetland wastewater treatment with disinfection via
      bioelectrochemical H2O2 production.

PMID- 23875316
TI  - A two-compartment photoelectrochemical cell for solar hydrogen production.

PMID- 23875317
TI  - Biomethane potential of agro-industrial substrates depends on the inoculum type.

PMID- 23875318
TI  - Fully automated monitoring tool to assess the activity and spatial distribution
      of broilers.

PMID- 23875319
TI  - Classification trees and support vector machines methods used to study habitat
      requirements of Azolla filiculoides (Lam.) in Selkeh Wetland, Iran.

PMID- 23875320
TI  - Use of support vector machines combines with genetic algorithm and greedy
      stepwise methods for prediction of habitat requirements of Azolla filiculoides
      (Lam.) in Selkeh wetland (Iran).

PMID- 23875321
TI  - Olive tree genetic background is a major cause of profilin (Ole e 2 allergen)
      polymorphism and functional and allergenic variability.

PMID- 23875322
TI  - Heritability of root traits of dwarf plantain hybrids.

PMID- 23875323
TI  - Study of a TiO2 photocatalytic coating for use in plasma catalysis.

PMID- 23875325
TI  - Dental education.

PMID- 23875324
TI  - Treatment of rainwater runoff in recovery and recyling companies: lab and pilot
      scale testing.

PMID- 23875326
TI  - Foundation of the BDA Benevolent Fund.

PMID- 23875327
TI  - The General Dental Council - fifty and counting.

PMID- 23875328
TI  - The United Kingdom dental trade.

PMID- 23875329
TI  - Petticoat practitioners: women in dentistry.

PMID- 23875330
TI  - Nicasio Etchepareborda (1857-1935).

PMID- 23875331
TI  - Generalleutnant Dr Karl Mauss (1898-1959).

PMID- 23875332
TI  - Origins of dental education in Ireland.

PMID- 23875333
TI  - Reminiscences of the North Yorkshire Local Dental Committee.

PMID- 23875334
TI  - Education at the British Dental Association Museum.

PMID- 23875335
TI  - Classification and measurement of malocclusion in the 19th century.

PMID- 23875336
TI  - James Sim Wallace (1869-1951): father of preventive dentistry.

PMID- 23875337
TI  - A story within history: Napoleon's mouth.

PMID- 23875338
TI  - Kenneth Cranston, 1917-2007: an appreciation.

PMID- 23875340
TI  - Two Mayfair dentists to royalty: 1775-1852.

PMID- 23875339
TI  - Ada Elizabeth Fletcher and the Ivory Cross.

PMID- 23875341
TI  - Dental educator.

PMID- 23875342
TI  - Dental education in Paris in the 1830s.

PMID- 23875344
TI  - The establishment of a dental hospital and a dental school in Manchester.

PMID- 23875343
TI  - National hospitals for dentures.

PMID- 23875345
TI  - Paul Revere (1735-1818), the "midnight rider".

PMID- 23875346
TI  - Leon Pereira (1859-1926).

PMID- 23875347
TI  - The Court report and child dental health.

PMID- 23875348
TI  - Collecting dental objects at the British Dental Association Museum.

PMID- 23875349
TI  - Dr William T Green Morton (1819-1868) and the American Civil War (1861-1865).

PMID- 23875350
TI  - The caries researcher and prosthodontist Hans Jacob Turkheim (1889-1955).

PMID- 23875352
TI  - Re: Issue No 48.

PMID- 23875351
TI  - Re: Issue No 47.

PMID- 23875353
TI  - The origins of Dental Historian.

PMID- 23875354
TI  - A century of orthodontics in the United Kingdom.

PMID- 23875355
TI  - Dental implants: past, present and future.

PMID- 23875356
TI  - The importance of books.

PMID- 23875357
TI  - Birmingham dental hospital's 150th anniversary*.

PMID- 23875358
TI  - Georges Paulin (1902-1942): legendary dentist and resistance hero.

PMID- 23875359
TI  - The rise and fall of area dental officers: specialists in public health
      dentistry?

PMID- 23875360
TI  - Why was Hayden Coffin? C R Coffin and sons in the late 19th and early 20th
      century.

PMID- 23875361
TI  - The Coffin plate and spring.

PMID- 23875362
TI  - Prof Orestes Walter Siutti, DipDent, PhD. Interview by Dr Diana Clara Daich de
      Eidelsztein.

PMID- 23875363
TI  - 'Royal chair' at Buckingham Palace.

PMID- 23875364
TI  - A caution to Psalm singers: jaw dislocation and advice in the Lancet.

PMID- 23875365
TI  - The dental hospitals of Manchester 1900-1939.

PMID- 23875366
TI  - Baron doctor Cornelius Ver Heyden De Lancey and Paul Hyland Harris: their
      cultural and artistic endeavours.

PMID- 23875368
TI  - Development of the norm concept in orthodontics.

PMID- 23875367
TI  - The dental service of the Red Army during World War II.

PMID- 23875369
TI  - 2012 Lilian Lindsay Memorial Lecture.

PMID- 23875370
TI  - Dental public health and John Stacy Bulman.

PMID- 23875371
TI  - Phosphorus jaw necrosis in the east end of London in the nineteenth and twenty
      first centuries.

PMID- 23875372
TI  - Creating the John Mclean archive: a living history of dentistry.

PMID- 23875373
TI  - Peter Heifer LDS, community orthodontist.

PMID- 23875374
TI  - Treatment of oral pain through the ages. 2011 Lilian Lindsay Memorial Lecture.

PMID- 23875375
TI  - The Bristol dental chair.

PMID- 23875376
TI  - Cardiff Dental School (1964-1971) an orthodontist's viewpoint.

PMID- 23875377
TI  - The great marine travels, scurvy and teeth.

PMID- 23875378
TI  - The life of Mrs Roper, a 19th century dentist.

PMID- 23875379
TI  - 19th century dentists in Malta: Matthew Cole Yeo.

PMID- 23875380
TI  - The Baron Doctor Cornelius Ver Heyden De Lancey and the women in his life.

PMID- 23875381
TI  - Thomas Rowlandson's transplanting of teeth: an analysis.

PMID- 23875382
TI  - History of the Belfast Dental School (1919-1965) [The 2002 Lilian Lindsay
      memorial lecture].

PMID- 23875385
TI  - Cover illustration of Dental Historian Number 54.

PMID- 23875384
TI  - Secretaries of the British Dental Association (Work in progress).

PMID- 23875383
TI  - The new cross school for dental auxiliaries (therapists From 1979) (1960-1983).

PMID- 23875386
TI  - The Royal Dental Hospital of Melbourne.

PMID- 23875387
TI  - Post office at the Melbourne dental hospital.

PMID- 23875388
TI  - Guy's hospital dental course (1944-1950) some thoughts from an ex-student.

PMID- 23875389
TI  - Re: Seated dentistry.

PMID- 23875390
TI  - Forensic identification of a damned couple: Adolf Hitler and Eva Braun.

PMID- 23875391
TI  - British 19th century dentists in Malta: John Mallan.

PMID- 23875392
TI  - The origin of the dental profession: dental disease and dentistry in ancient
      Egypt.

PMID- 23875393
TI  - Oral and maxillofacial surgery at the London hospital (1857-1990).

PMID- 23875395
TI  - Prof Dr Oscar Sixto Bonal.

PMID- 23875394
TI  - The Bristol Dental School site.

PMID- 23875396
TI  - In search of Dracula's teeth.

PMID- 23875397
TI  - Tooth development in cattle: University of Illinois (1957-1959).

PMID- 23875399
TI  - Thank you Imhotep.

PMID- 23875398
TI  - Napoleon II (1811-1832) and his teeth.

PMID- 23875400
TI  - 19th century British Dentists in Malta: David and James Finnie.

PMID- 23875401
TI  - Evolution of dental phantoms in Manchester.

PMID- 23875402
TI  - Hugh Leech and his war-time diaries (1939-1944).

PMID- 23875403
TI  - Sir John Tomes (1815-1895).

PMID- 23875404
TI  - The dentists of Llandysul 1900-2000.

PMID- 23875405
TI  - Crawford Dental Collection at Museum of Health care at Kingston, Ontario.

PMID- 23875406
TI  - Evocative account of James Scott.

PMID- 23875407
TI  - Seated dentistry.

PMID- 23875408
TI  - Alexander 'Pete' Suer (1917-1945): dentist and Second World War hero.

PMID- 23875409
TI  - Tom Brown: a Victorian general dental practitioner.

PMID- 23875410
TI  - The British Association for the Study of Community Dentistry and the specialty of
      dental public health.

PMID- 23875411
TI  - James Henderson Scott (1913-1970): charismatic teacher*.

PMID- 23875412
TI  - Pen pictures of 19th century dentists in Malta: Thomas John Jenkin (1842-1917).

PMID- 23875413
TI  - Introduction to methods of oral history.

PMID- 23875414
TI  - Pulp capping and pulpotomy: 1750 - 2008.

PMID- 23875415
TI  - Professor Varaztad Hovhannes Kazanjian (1879-1974).

PMID- 23875416
TI  - Pen pictures of 19th century dentists in Malta: Noble Sparks.

PMID- 23875417
TI  - Re: Moody.

PMID- 23875418
TI  - Roeko.

PMID- 23875420
TI  - A short history of forensic dentistry.

PMID- 23875421
TI  - E H Angle - a British perspective.

PMID- 23875422
TI  - An homage to the first African-American dentists.

PMID- 23875423
TI  - Painted faces.

PMID- 23875424
TI  - Great Ormond Street Hospital, its dental surgeons (1856-1946) and the Cartwright
      family.

PMID- 23875425
TI  - Army dentistry to the end of World War II.

PMID- 23875426
TI  - National Service in the Royal Army Dental Corps in Nigeria 1951-1953.

PMID- 23875427
TI  - One hundred and fifty years of the Odontological Collection.

PMID- 23875428
TI  - Back on the same page ... maybe not.

PMID- 23875429
TI  - The use of interim therapeutic restorations in the virtual dental home system.

PMID- 23875430
TI  - Disclosure.

PMID- 23875431
TI  - Salt fluoridation: a review.
AB  - Salt fluoridation is sometimes suggested as a prospect for communities that have
      a low water fluoride concentration and have no possibility of implementing
      community water fluoridation. School-based milk fluoridation programs also are
      practiced in some countries as an alternative. This paper reviews the evidence of
      effectiveness in dental caries prevention and risks of dental fluorosis in
      countries where salt or milk fluoridation is practiced.

PMID- 23875432
TI  - CAD/CAM complete dentures: a review of two commercial fabrication systems.
AB  - The use of computer-aided design and computer-aided manufacturing (CAD/CAM) has
      become available for complete dentures through the AvaDent and Dentca systems.
      AvaDent uses laser scanning and computer technology. Teeth are arranged and bases
      formed using proprietary software.The bases are milled from prepolymerized pucks
      of resin. Dentca uses computer software to produce virtual maxillary and
      mandibular edentulous ridges, arrange the teeth and form bases. The dentures are
      fabricated using a conventional processing technique.

PMID- 23875433
TI  - Management of antithrombotic therapy before full-mouth extraction.
AB  - The management of antiplatelet and anticoagulant therapy before full-mouth
      extraction is a major concern for dentists. Approach should vary depending on the
      risk of bleeding and adverse cardiac events. We have adapted a more conservative
      approach with continuation of antiplatelet therapy in the majority of patients
      while implementing local hemostatic measures with good outcomes. Specific
      recommendations are provided for antiplatelet therapy before mouth extraction.

PMID- 23875435
TI  - Salt fluoridation -an adjunct to water fluoridation.

PMID- 23875434
TI  - Meth mouth severity in response to drug-use patterns and dental access in
      methamphetamine users.
AB  - Meth mouth is the rapid development of tooth decay in methamphetamine users. Our
      study questioned whether drug-use patterns and dental care access are risk
      factors affecting the severity of meth mouth. Participants received dental
      examinations, and the number of decayed, missing and filled teeth (DMFT) were
      counted and used to measure meth mouth severity.

PMID- 23875436
TI  - Is anybody out there?

PMID- 23875438
TI  - More rapid testing group B streptococcus detection.

PMID- 23875437
TI  - Non-invasive prenatal aneuploidy testing: technologies and clinical implication.

PMID- 23875439
TI  - Automated HER2 testing: personalized healthcare for breast cancer patients
      enabled by novel molecular morphology methods.

PMID- 23875440
TI  - Is your lab inspection-ready?

PMID- 23875441
TI  - Improving anatomic pathology outreach for the hospital lab.

PMID- 23875442
TI  - Eco-friendly waste management.

PMID- 23875443
TI  - Real time PCR I: the dyes that bind.

PMID- 23875444
TI  - Rapid methods for pathogen detection in blood stream infections.

PMID- 23875445
TI  - New York vs sepsis: a bold first step means new protocols and testing.

PMID- 23875446
TI  - Blood cultures and the detection of sepsis.

PMID- 23875447
TI  - The end of sequestration! well, not exactly. Read on.

PMID- 23875448
TI  - Integrating clinical genomics into the standard of care for medical providers.

PMID- 23875450
TI  - DNA damage response, checkpoint activation and dysfunctional telomeres: face to
      face between mammalian cells and Drosophila.
AB  - Eukaryotic cells evolved telomeres, specialized nucleoproteic complexes, to
      protect and replicate chromosome ends. In most organisms, telomeres consist of
      short, repetitive G-rich sequences added to chromosome ends by a reverse
      transcriptase with an internal RNA template, called telomerase. Specific DNA
      binding protein complexes associate with telomeric sequences allowing cells to
      distinguish chromosome ends from sites of DNA damage. When telomeres become
      dysfunctional, either through excessive shortening or due to defects in the
      proteins that form their structure, they trigger p53/pRb pathways that limits
      proliferative lifespan and eventually leads to chromosome instability. Drosophila
      lacks telomerase, telomeres are assembled in a sequence-independent fashion and
      their length is maintained by transposition of three specialized retroelements.
      Nevertheless, fly telomeres are maintained by a number of proteins involved in
      telomere metabolism as in other eukaryotic systems and that are required to
      prevent checkpoint activation and end-to-end fusion. Uncapped Drosophila
      telomeres induce a DNA damage response just as dysfunctional human telomeres.
      Most interestingly, uncapped Drosophila telomeres also activate the spindle
      assembly checkpoint (SAC) by recruiting the SAC kinase BubR1. Here we review
      parallelisms and variations between mammalian and Drosophila cells in the
      crosstalks between telomeres and cell cycle regulation.

PMID- 23875451
TI  - [Ability of Su(Hw) to create a platform for ORC binding does not depend on the
      type of surrounding chromatin].
AB  - DNA replication begins from multiple sites distributed thoughout the genome and
      named replication origins. Despite the increasing amount of data on the
      properties of replication origins, it is still unknown what factors(s) is the
      primary determinant of ORC localization. Su(Hw) is a zinc-finger protein that is
      responsible for the activity of the best-studied Drosophila insulators. Here, we
      show that insulator protein Su(Hw) recruits histone acetyltransferase complex
      SAGA and chromatin remodeler dSWI/SNF to Su(Hw)-dependent insulators and creates
      platform for ORC binding. We have found that Su(Hw) is necessary for chromatin
      remodeling and ORC recruitment regardless of type of surrounding chromatin. Thus,
      global chromatin state does not influence molecular mechanism underlying ORC
      positioning in the genome, rather DNA-binding proteins are key determinants that
      create proper chromatin structure for ORC binding. Su(Hw) is the first example of
      such a protein.

PMID- 23875452
TI  - [Grass genome and chromosome sets evolution].
AB  - This paper briefly discusses the mechanisms by which either diploid 2n or basal
      chromosome number x change during grass karyotype evolution.

PMID- 23875453
TI  - [Organization and evolution of the subtelomeric regions of the rye chromosomes].
AB  - Subtelomeric regions of chromosomes are particularly dynamic and variable parts
      in the evolution of the eukaryotic genomes. A specific feature of the rye
      (Secale) chromosomes is large heterochromatin blocks at the arms of all seven
      pairs of chromosomes. Within the genus Secale, an interspecific variation in the
      genome size reaches nearly 15% between Secale cereale (cultivated rye) and the
      ancient species S. silvestre and an increase in the size of subtelomeric
      heterochromatin regions is the main contributor to these differences. Earlier
      works have demonstrated that the subtelomeric hetechromatin of rye is enriched
      for a few multicopy tandemly organized DNA families which form the long arrays of
      monomers. Here we aimed to clarify the fine large-scale organization and mutual
      arrangement within the tandem arrays of these families and the flanking genomic
      nonarray DNA. Restriction analysis of the BAC-clones containing genetic material
      of the short arm of the first rye chromosome (1RS) showed that within arrays the
      bulk of monomers is organized in the specific higher-order repeat units (up to
      hexamers) which are generated in the central part of tandem arrays, while only
      monomers and dimers are present near the boundaries. Sequencing of the genomic
      nonarray DNA flanking the tandem arrays has demonstrated that this DNA in the
      studied BAC-clones consists completely of retrotransposons of various classes
      which are also present in the wheat and barley genomes. Thus, only an explosive
      amplificcation ofpSc200 and pSc250 monomers, on the background of a saturated
      mixture of various retrotransposons, can be regarded as a specific molecular
      process in formation of subtelomeric hetechromatin during the divergence of rye
      genome from the common ancestor of cereals. Evidently, this process resulted in
      the enlargement of subtelomeric hetechromatin of S. cereale and an increasing of
      its genome size.

PMID- 23875454
TI  - [Epigenetic regulation of expression of vernalization genes].
AB  - We reviewed the mechanisms of epigenetic regulation of vernalization genes of
      plants which control the transition to the generative stage, depending on the low
      temperatures. Based on the example of FLC-gene of Arabidopsis, the involvement of
      the PR2 repression complex and non-coding RNAs in these mechanisms has been
      shown. On the basis of our own and other data, the authors suggest a similar
      mechanism of regulation of Vrn-1 gene of cereals.

PMID- 23875455
TI  - Chromosome phylogenies of malaria mosquitoes.
AB  - Malaria mosquitoes often belong to complexes of sibling species, members of which
      are morphologically and genetically similar to each other. However, members
      within these complexes can vary significantly in their ecological adaptations and
      abilities to transmit the malaria parasite. The high degree of genetics
      similarity among sibling species makes the reconstruction of phylogenetic
      relationships within species complexes difficult. This paper reviews studies that
      infer the ancestral--descendant relationships among sibling species using
      molecular markers and chromosomal inversions. A methodology based on analyzing
      breakpoints of fixed overlapping inversions is shown to be useful for rooting
      phylogenies in complexes of sibling species, if the chromosomal arrangements in
      outgroup species are known. The construction of detailed phylogenies for malaria
      vectors will help to identify the association of evolutionary genomic changes
      with the origin of human blood choice and specific ecological adaptations.

PMID- 23875456
TI  - Progress in mapping the yellow fever mosquito genome.
AB  - Mosquito-borne diseases cause significant problems for the human health. For this
      reason, the genomes of three most dangerous species of mosquitoes, including the
      yellow fever mosquito Aedes aegypti, were sequenced in last decade. The efficient
      vector of arboviruses. Ae. aegypti, is also a convenient model for laboratory
      research. The intensive genetic mapping of morphological and molecular markers
      conducted for this mosquito in the past was very successful. This mapping was
      also used as a tool to localize a number of quantitative trait loci related to
      the mosquito's ability to transmit various pathogens. However, physical mapping
      of the Ae. aegypti genome is difficult due to the lack of high-quality polytene
      chromosomes. Here, we review different mapping approaches that help improving
      genome sequence assembly and also integrate linkage, chromocome and genome maps
      the yellow fever mosquito.

PMID- 23875457
TI  - [Dynamics of chromosome number evolution in the Agrodiaetus phyllis species
      complex (Insecta: Lepidoptera)].
AB  - We employed phylogenetic comparative method to study karyotype evolution in the
      Agrodiaetus phyllis species complex in which haploid chromosome numbers vary
      greatly ranging from 10 to 134. We have found that different phylogenetic
      lineages of the group have different rates of chromosome number changes.
      Chromosome numbers in the complex posses phylogenetic signal, and their
      evolutionary transformation is difficult to explain in terms of punctual and
      gradual evolution.

PMID- 23875458
TI  - [Telomere length and phylogenetic relationship of Baikal and Siberian planarians
      (Turbellaria, Tricladida)].
AB  - Dynamics of the telomeric DNA (tDNA) and the phylogeny of the Baikal and Siberian
      planarians have been studied based on the analysis of the 18S rDNA and beta-actin
      gene fragments. A relationship between tDNA and the planarians size has been
      demonstrated. Giant planarians with a minor exception have longer tDNA than
      little planarians. Phylogenetic affinity between the species that have the
      stretched tracks of tDNA, big size and similar habitats may indicate possible
      role of tDNA in the development of the indefinite regenerative capacity of
      planarians.

PMID- 23875459
TI  - [Genomic structure and sex determination in squamate reptiles].
AB  - Squamata is the largest reptilian order including snakes and lizards which
      occupies a key position in phylogeny of amniotes. A variety of sex determination
      modes in lizards is one of the most interesting parts of the biology of this
      order. These mechanisms are genomic sex determination (both XY and ZW systems)
      and temperature-dependent sex determination. Studies of squamata sex chromosomes
      are pivotal for understanding evolution of other vertebrate sex chromosomes.
      Unfortunately, this clade has long been neglected by molecular geneticists. In
      this paper, we describe recent data on molecular cytogenetics and genomics of
      squamates, evolution of their sex chromosomes and sex determination mechanisms.

PMID- 23875460
TI  - Murine multicolor banding.
AB  - Multicolor banding approach, first introduced for human chromosomes only, was
      established as an optimal approach for karyotyping of murine chromosomes. Here we
      present the established mcb probe sets for all murine autosomes and the X
      chromosome and review their potential application.

PMID- 23875461
TI  - [Chromosomal variability of the Maximowicz's vole Microtus maximowiczii
      (Rodentia, Cricetidae, Microtus)].
AB  - The numeration of the chromosomes, which can be used to describe the karyotypes
      of various chromosomal forms from different geographical regions, has been
      proposed for the Maximowicz's vole Microtus maximowiczii. Application of FISH
      analysis has allowed us to show homology of Robertsonian rearregement (11/20)
      inkaryotypes of voles from Transbaikalia (2n = 41 and voles from Norsky
      reservation in Amur Region (2n = 40).

PMID- 23875462
TI  - [Karyotype evolution of suborder (Ruminantia)].
AB  - Suborder Ruminantia is the largest taxa in order Cetartiodactyla and includes
      species with great differences in morphology and diploid numbers of chromosomes.
      To date, the main chromosome changes that formed karyotypes of modern species of
      this suborder have been described by comparative chromosome painting. This paper
      provides a brief review of the features of the evolution of Ruminantia
      karyotypes.

PMID- 23875463
TI  - [Molecular cytogenetic markers of cryptic species and hybrids of the common vole
      superspecies complex Microtus arvalis s. l].
AB  - Molecular markers of cryptic cytogenetical differentiation were shown in
      chromosomal polymorphic Pan-European model group of rodents Microtus arvalis s.
      l. by FISH analysis. The polytypy of 46-chromosomes karyotypes determined by the
      sites of interstitial telomeric sequences (ITS) and ribosomal DNA emphasizes the
      genetical isolation of M. arvalis s. s. and M. obscurus.

PMID- 23875464
TI  - Cytogenetic analysis of a hybrid zone between the Moscow and Neroosa races of the
      common shrew (Sorex araneus) differing by a single wart-like chromosome
      rearrangement.
AB  - Three karyotypic variants were revealed in the Moscow-Neroosa chromosomal hybrid
      zone by comparative cytogenetic analysis: homozygotes of the pure parental races
      and complex heterozygotes (F1 hybrids). As expected, a ring-of-four configuration
      (RIV) was observed in diakinesis spreads of hybrids. No disturbances in the
      structure of the RIV were found. Distribution of telomeric repeats and rDNA on
      the chromosomes of an individual of the Neroosa race were studied using dual
      colour FISH.

PMID- 23875465
TI  - [The peculiarities of the chromosome organization in meiosis].
AB  - Meiotic and mitotic chromosomes differ in a number of features. 1. At the early
      prophase I of meiosis, chromosomes acquire proteinaceous axial elements (AEs)
      which were absent at mitosis. In addition to somatic cohesins, AEs contain
      meiosis-specific cohesins REC8, SMC1beta, STAG3. 2. At the middle prophase I,
      proteinaceous lateral elements (LEs) of synaptonemal complexes (SC) are shaped on
      a basis of AEs. Proteins of LEs are not conserved, but in Saccharomyces
      cerevisiae and Arabidopsis thaliana they contain functional domains with
      conserved secondary structure. Proteins or functional domains similar to SC
      proteins have been found in green and brown algae, some of lower fungi and in
      Coelenterata amongs about 679 hundreds of proteins of primitive eukaryotes
      studied with bioinformatic methods. 3. During the pachytene and diplotene stages
      of meiosis, chromosomes of spermatocytes and mother pollen cells acquire the
      structure resembling in miniature the structure of amphibian and avian lamp brush
      chromosomes. Lateral chromatin loops of 90, 160 and more than 480 Kb in size are
      observed in human spermatocytes during the diplotene stage. Taken together, these
      findings support the idea of considerable conservation of the scheme of molecular
      and ultrastructural organization of meiotic chromosomes in a variety of
      eukaryotic organisms.

PMID- 23875466
TI  - [Achievement and prospects of the new laboratory of medical cytogenetics].
AB  - Chromosomal abnormalities (CA) represent a significant part in the congenital and
      hereditary diseases of man. Because of the high need for cytogenetic analysis in
      January, 2011 a new cytogenetic laboratory was established in ICBFM SB RAS. For 1
      year and 8 months more than 450 people was examined (including 21 cases with
      prenatal diagnosis (PD)), and 34 cases of CA was revealed. The diagnostics allows
      to choose symptomatic treatment for patients with CA or to prevent the birth of a
      child with serious CA and to plan a family. Our future plans is to develop of PD
      (amniocentesis) and to use the methods of molecular cytogenetic.

PMID- 23875467
TI  - [A novel NF-kappaB regulatory mechanism targeting a polyubiquitin chain].

PMID- 23875468
TI  - [Linear ubiquitination-mediated NF-kappaB regulation and its related diseases].

PMID- 23875470
TI  - [The change in 3-dimensional intracellular parameters alters oscillation pattern
      of nuclear NF-kappaB].

PMID- 23875469
TI  - [Structural biology of ubiquitin signaling].

PMID- 23875471
TI  - [Cell-free based protein array technology for analyses of protein kinases and
      ubiquitin ligases].

PMID- 23875472
TI  - [Highly sensitive detection method for protein phosphorylation and its
      development as a new technique toward phosphoproteomics].

PMID- 23875473
TI  - [High-resolution signal transduction networks revealed by shotgun proteomics
      technology].

PMID- 23875474
TI  - [Regulation of receptor tyrosine kinases by Ser/Thr phosphorylation].

PMID- 23875475
TI  - [Signal transduction in melanoma].

PMID- 23875476
TI  - [Cancer targeted therapy and resistance signals].

PMID- 23875477
TI  - Why the march on genetically modified food hurts the hungry.

PMID- 23875478
TI  - The high-deductible trap. Will the increasingly popular option undermine
      accountable care?
AB  - High-deductible health plans are on the rise, but patients fearful of upfront
      costs can be reluctant to seek care under the plans. That undermines the goals of
      accountable care, which rely on timely care. "What the high-deductible health
      plans do is they very effectively address the cost of care, but they don't have a
      positive impact on the quality of care or on access," says Dr. David Shulkin,
      left, president of the Atlantic Accountable Care Organization.

PMID- 23875479
TI  - Enrollment challenge. Insurers, providers take on expansion promotion.

PMID- 23875480
TI  - Pace of obesity growth slows. Federal efforts cited, but 'lot more work to be
      done'.

PMID- 23875481
TI  - Back to government. Berwick discusses his run for Mass. governor, goals for
      healthcare reform.

PMID- 23875482
TI  - Tipping point. Nation's EHR use tops 50%, stage set for next steps.

PMID- 23875483
TI  - Code worry. Docs say ICD-10 implementation carries hefty cost.

PMID- 23875484
TI  - Big data and big government. Strong federal role needed to organize productive
      use of patient data.

PMID- 23875485
TI  - Even in healthcare, quality is free. By focusing on patients, their satisfaction
      and your income will improve.

PMID- 23875486
TI  - Beyond ACOs. Financial risk and capital hurdles are cited as reasons many
      providers aren't joining accountable care organizations, but some are finding
      other routes to payment reform.

PMID- 23875488
TI  - Largest healthcare law firms. Based on a blended score of healthcare lawyers
      employed in 2012 and AHLA membership as of June 3.

PMID- 23875487
TI  - Curing technical violations. Stark law exception would let hospitals disclose,
      resolve paperwork infractions.

PMID- 23875489
TI  - A penny for your thoughts.

PMID- 23875490
TI  - An endowed chair in physician assistant studies.

PMID- 23875491
TI  - Physician assistant education: an analysis of the Journal of Physician Assistant
      Education.
AB  - PURPOSE: The literature of a profession reflects its vitality, activity, and
      intellectual temperature. A thorough review of literature can reveal areas of
      growth and improvement as well as serve as a means to share relevant research
      accomplishments. As the physician assistant (PA) education profession continues
      to thrive and expand, it is important for the literature that reflects the
      profession to also develop and expand its audience. METHODS: A retrospective,
      systematic analysis of published research articles in the Journal of Physician
      Assistant Education (JPAE) and its predecessor publication, Perspective on
      Physician Assistant Education, from 2001-2011 (N = 145) was conducted. Articles
      were organized by study topic, cohort of interest, and methodology and further
      analyzed to determine respective response rates and frequency of topics. RESULTS:
      Nearly one-fourth of all articles considered were dedicated to studying various
      PA curricula. Methodological approaches used in these studies tended toward
      Internet-based surveys, but telephone-based surveys retained the highest response
      rate (97%). Among study subjects (cohorts) examined, the most frequently studied
      cohort consisted of PA students, who displayed high response rates (74.4%).
      CONCLUSION: The total number of articles published in JPAE increased annually;
      study methodology reflects a predominance of survey research approaches. Analysis
      from this review of 10 years of JPAE content suggests that studies using
      effective methodology to gain high response rates, those that have more
      sophisticated designs and use appropriate statistical measures, and those that
      aim to reach a more diverse pool of cohorts may be future goals.

PMID- 23875492
TI  - To teach or not to teach: 2011 national survey of physician assistants and
      preceptor experiences.
AB  - PURPOSE: The availability of clinical preceptors is essential for education and
      workforce planning. The purpose of this study is to describe the proportion and
      the characteristics of physician assistants (PAs) involved as preceptors. It also
      aims to identify the most important incentives and barriers for PAs to precept
      students. METHODS: A cross-sectional study was conducted with certified PAs in
      the United States from March 2011 to May 2011. An anonymous survey was sent via
      email to the 76,527 PAs in the National Commission on Certification of Physician
      Assistants' database. A total of 11,722 unique responses was received, yielding
      an overall response rate of 15.3%. RESULTS: Only 25% of clinically active PAs
      self-identified as current preceptors of PA students in 2011. The most common
      characteristics of current preceptors were male gender, practicing full-time,
      working in a teaching hospital, providing inpatient care, and having more than 6
      years of clinical practice. The most important incentives to consider precepting
      more students among all respondents were the quality of the students and the
      ability to earn CME category I credit. In contrast, the most important reported
      barriers were lack of support by either supervising physician or administrators.
      Preceptors and nonpreceptors ranked certain incentives and barriers differently.
      CONCLUSIONS: The proportion of PAs who are clinical preceptors is low. Knowing
      the differences in the characteristics and attitudes between PA preceptors and
      nonpreceptors will help inform future recruitment and retention efforts.
      Qualitative research is underway to further explore quantitative study findings.

PMID- 23875493
TI  - A conversation with E. Harvey Estes, MD. Interview by James F Cawley.

PMID- 23875494
TI  - Physician assistant program education on spirituality and religion in patient
      encounters.
AB  - PURPOSE: To describe educational practices of physician assistant (PA) programs
      regarding spirituality and religion discussions during patient encounters.
      Patients want their health care provider to be aware of their spiritual and
      religious beliefs. This topic is addressed in physician and nursing education but
      may not be included in PA programs. METHODS: Data regarding curriculum were
      collected via electronic survey emailed to 143 PA programs across the United
      States. RESULTS: Thirty-eight programs responded for a response rate of 27%. Most
      (68.4%) program respondents reported students' desire to be trained to discuss
      spirituality and religion, yet 36.8% do not offer this training. Just over half
      (69.2%) would consider adding curriculum to teach students to discuss
      spirituality, but the majority (92.3%) would not add curriculum to discuss
      religion during patient encounters. CONCLUSION: PA programs offer training to
      discuss spirituality in patient encounters but not to discuss religiosity.
      Programs may want to consider adding some curriculum to increase PAs awareness of
      spirituality and religion needs of patients.

PMID- 23875496
TI  - Physician assistant education in Germany.
AB  - The first physician assistant (PA) program in Germany began in 2005. As of 2013
      there are three PA programs operational, with a fourth to be inaugurated in the
      fall of 2013. The programs have produced approximately 100 graduates, all with a
      nursing background. The PA model of shifting tasks from medical doctors to PAs
      appears to be growing among senior physicians and hospital administrators. While
      the development of a German PA movement is in its nascent stage, the training,
      deployment, and evolution of PA training programs appears underway.

PMID- 23875495
TI  - Integrating cultural competency throughout a first-year physician assistant
      curriculum steadily improves cultural awareness.
AB  - PURPOSE: This study tracked student self-assessments of cultural awareness at
      regular intervals during the first year of a master's of science physician
      assistant (PA) program to test effectiveness of a cultural competency component
      in the curriculum. METHOD: Students completed a cultural awareness survey at the
      beginning of the program and retook the survey at approximately 4-month intervals
      throughout the first year. RESULTS: Regression analyses confirmed positive linear
      relationships between survey number and score on 31 of 31 items. CONCLUSION:
      Cultural awareness among PA students benefits from repeated exposures to lessons
      on cultural competency. Schools attempting to develop or expand cultural
      awareness among students should consider presenting material in multiple courses
      across terms.

PMID- 23875497
TI  - Are physician assistant educators prepared to facilitate master's level research
      among their students?

PMID- 23875498
TI  - The role of physician assistants on institutional ethics committees.

PMID- 23875499
TI  - Incorporating electronic medical records into the physician assistant educational
      curriculum.

PMID- 23875500
TI  - The IRS and "your health care".
AB  - At most times, the IRS is one of America's least loved institutions, but this
      past month has been a particularly bad period for the agency.

PMID- 23875501
TI  - 5 ways to minimize duplicate patient records.
AB  - Realizing that data integrity and patient information accuracy are crucial to
      proper payment, Texas Health Resources reduced its duplicate patient records by
      21 percent to achieve cleaner claims and faster cash flow. Here are five ways the
      13-hospital system met this challenge.

PMID- 23875503
TI  - How to manage a hospital PR crisis. Interviewed by Gini Dietrich.
AB  - Action steps hospitals and health systems should take to prepare for a public
      relations (PR) crisis include the following: Develop a plan for dealing with PR
      crises that establishes a central incident command center and sets forth clear
      lines of authority and responsibility. Provide the name, phone number, email
      address, and other contact information for a knowledgeable person who can respond
      to media inquiries. Act fast--within a couple of hours--to explain the facts.

PMID- 23875502
TI  - ICD-10: cracking the code.
AB  - Healthcare organizations should address physician clinical documentation
      improvement now, before the Oct. 1, 2014, implementation deadline for ICD-10, if
      they are to mitigate risk related to ICD-10 and optimize operational processes.
      Improving documentation now will have an immediate effect on revenue and will
      minimize the potential for losses related to denied claims after ICD-10 goes into
      effect. Training of physicians should not be just a "once-and-done" process.
      Organizations should plan now for training to continue even after the
      implementation deadline.

PMID- 23875504
TI  - Navigating performance-based risk.
AB  - Numerous factors contribute to an organization's "risk tolerance" under
      performance-based risk arrangements, including its size, patient population, and
      the strength of its financial position. There are three types of risk inherent in
      value-based contracting: Financial risk. Actuarial risk. Strategic risk.

PMID- 23875505
TI  - Mitigating risks related to facilities management.
AB  - By looking at metrics focusing on the functionality, age, capital investment,
      transparency, and sustainability (FACTS) of their organizations' facilities,
      facilities management teams can build potential business cases to justify
      upgrading the facilities. A FACTS analysis can ensure that capital spent on
      facilities will produce a higher or more certain ROI than alternatives. A
      consistent process for managing spending helps to avoid unexpected spikes that
      cost the enterprise more in the long run.

PMID- 23875506
TI  - Overcoming 4 common revenue cycle benchmarking myths.
AB  - Peer group comparisons can help revenue cycle leaders: Review their performance
      through an external lens. Set targets and motivate their teams. Provide informed
      answers to questions from the C-suite.

PMID- 23875507
TI  - Revisiting gainsharing.
AB  - Gainsharing initiatives stalled in the past due to legal concerns, but they are
      enjoying a renaissance as part of broader initiatives, such as accountable care
      organizations and bundled payments. In the past, with so much of the focus on the
      legal aspects of gainsharing, the potential of gainsharing to preserve physician
      choice, reduce costs, and maintain or improve quality may have been
      underestimated. A gradual gainsharing rollout tailored to the needs of various
      clinical areas can boost an organization's prospects for success.

PMID- 23875508
TI  - Financing strategic plans for not-for-profits.
AB  - To succeed in today's complex economic environment, a not-for-profit health
      system requires an effective strategic capital planning process that harmonizes
      three elements: The organization's long-term business plan and mission. Existing
      financial resources and finance options available to support the organization's
      business plan. Financial risk and return on equity to the organization's
      stakeholders (within acceptable parameters for business risk).

PMID- 23875509
TI  - How to reduce the risk of purchasing fraud.
AB  - Purchasing fraud leads to significant losses for healthcare entities and damages
      the reputation of the industry. Designing and implementing an effective internal
      control environment helps reduce the risk of fraud. An effective control
      environment includes a variety of policies, procedures, strategies, and tactics.

PMID- 23875510
TI  - TBIs: an emerging risk for health systems.
AB  - Healthcare providers should take eight steps to ensure their organizations are
      prepared for the potential risks associated with traumatic brain injuries: Review
      current procedures. Educate parents and caregivers. Create targeted programs for
      seniors. Adopt standard written protocols for providers for identification and
      treatment. Ensure proper and periodic follow-up with all patients at risk. Add a
      question about recent falls and head injuries to the patient intake discussion
      sheet. Conduct thorough debriefings and analyses following confirmed TBIs.
      Evaluate the organization's current insurance policy to ensure it provides the
      coverage needed.

PMID- 23875511
TI  - The value-driven revenue cycle.
AB  - Conversations on improving the value of health care often focus on clinical
      performance improvement efforts. Yet during Phase 2 of HFMA's Value Project
      research, CFOs time and again identified the revenue cycle as the place where
      their hospital's performance improvement efforts have begun.

PMID- 23875512
TI  - Marginal complications and healthcare costs.
AB  - In a recent study published in JAMA, the authors concluded that hospitals might
      have financial disincentives for reducing surgical complications. The study
      confirms some well-known healthcare financial management realities: Some
      procedures are more profitable than others, and sometimes complications generate
      positive returns for hospitals. But the study was flawed.

PMID- 23875513
TI  - National trends in charges, cost, and Medicare IPPS payment.

PMID- 23875515
TI  - Membrane potential and pH-dependent accumulation of decynium-22 (1,1'-diethyl
      2,2'-cyanine iodide) flourencence through OCT transporters in astrocytes.
AB  - 1,1 '-Diethyl-2,2'-cyanine iodide (decynium22; D22) is a potent blocker of the
      organic cation family of transporters (EMT/OCT) known to move endogenous
      monoamines like dopamine and norepinephrine across cell membranes. Decynium22 is
      a cation with a relatively high affinity for all members of the OCT family in
      both human and rat cells. The mechanism through which decynium22 blocks OCT
      transporters are poorly understood. We tested the hypothesis that denynium22 may
      compete with monoamines utilizing OCT to permeate the cells. Using the ability of
      D22 to aggregate and produce fluorescence at 570 nm, we measured D22 uptake in
      cultured astrocytes. The rate of D22 uptake was strongly depressed by acid pH and
      by elevated external K+. The rate of uptake was similar to that displayed by 4-(4
      (dimethylamino)-styryl)-N-methylpyridinium (ASP+), a well established substrate
      for OCT and high-affinity Na+-dependent monoamine transporters. These data were
      supported by measurement of electrogenic uptake using whole cell voltage clamp
      recording. Decynium22 depressed norepinephrine, but not glutamate uptake. These
      data are also consistent with the described OCT transporter characteristics.
      Taken together, our results suggest that decynium22 accumulation might be a
      useful instrument to study monoamine transport in the brain, and particularly in
      astrocytes, where they may play a prominent role in monoamine uptake during brain
      dysfunction related to monoamines (like Parkinson disease) and drug addiction.

PMID- 23875516
TI  - Prevalence of drug resistance and associated mutations in a population of Hiv-1+
      Puerto Ricans in 2005.
AB  - This is a continuation of our efforts to maintain a record of the evolution of
      HIV-1 infection in Puerto Rico by monitoring the expression levels of
      antiretroviral resistance-associated mutations. Samples from 2005 were analyzed
      (458: 270 males, 137 females, 51 anonymous), using the TRUGENE HIV-1 Genotyping
      Kit and the OpenGene DNA Sequencing System. Results show that 60.1% of males and
      50.2% of females had HIV-1 with resistance to at least one medication. The
      average number of HIV mutations in males was 6.27, while the average number of
      HIV mutations in females was 5.49. The highest levels of resistance were to
      Zalcitabine, Lamivudine, and Stavudine. The reverse transcriptase mutations with
      the highest frequency of expression were M184V, K103N and D67N. Protease
      mutations with the highest rate of expression were L63P, M361 and L90M.
      Significant differences between men and women were recorded in the levels of HIV
      1 expressed mutations and resistance.

PMID- 23875517
TI  - Effects of gravitational perturbation on the expression of genes regulating
      metabolism in Jurkat cells.
AB  - Gravitational pertubation altered gene expression and increased glucose
      consumption in spaceflown Jurkat cells. The purpose of this study was to
      determine if the acceleration experienced during launch was responsible for these
      changes. In ground-based studies, cells were subjected to typical launch
      centrifugal acceleration (3g of force for eight minutes) and centrifugal force of
      90g for five minutes (commonly used to sediment cells) in a laboratory
      centrifuge. Controls consisted of static cultures. Gene expression was analyzed
      by RT-PCR. pH and glucose concentrations were evaluated to monitor metabolic
      changes. Comparison with controls indicated no significant change in pH or
      glucose use. Gene expression of Jurkat cells subjected to 3g or 90g of force was
      altered for only two genes out of seven tested. This research suggests that the
      changes observed in Jurkat cells flown on STS-95 were not a result of launch
      acceleration but to other conditions experienced during space flight.

PMID- 23875518
TI  - Cardiovascular events during general elections in Bayamon, Puerto Rico.
AB  - Emotional stress has been linked to acute coronary events. We examined whether
      the emotional response to elections in Puerto Rico induced a similar response.
      METHODS: We reviewed records at HIMA San Pablo Hospital (HIMASP) and Ramon Ruiz
      Arnau University Hospital (HURRA) in Bayamon and identified patients admitted
      with ICD-9 codes 410, 411, and 413 or corresponding diagnoses during a period
      surrounding the general elections and compared them with the same time period in
      non-election years. RESULTS: Cardiovascular events accounted for 3.24% of
      election-year admissions vs. 5.51% during non-election years in HURRA (p=0.036,
      N=37), while accounting for 2.86% of election-year admissions in HIMASP vs. 3.27%
      during non-election years (non-significant). DISCUSSION: There was a trend
      towards a lower rate of admission for cardiovascular events during general
      elections in both hospitals, reaching statistical significance at HURRA. Further
      study may elucidate reasons for this behavior and determine whether similar
      trends hold true in other populations.

PMID- 23875519
TI  - Gender differences in social and developmental factors affecting Puerto Rican
      adolescents during the early stage.
AB  - BACKGROUND: Adolescence is associated with risky behaviors related with social
      and developmental factors. Objectives were to describe social and developmental
      factors affecting Puerto Rican early adolescent by gender and type of school at
      study entry. METHODS: Cross-sectional study design. The study group was composed
      by 168 seventh grade adolescents from private and public schools. Descriptive and
      non-parametric comparisons were performed. RESULTS: Significance differences
      among proportions for gender by type of school were found in the following
      variables: self-esteem and HIV/AIDS attitudes in public school and peer pressure
      and sensation seeking in private school. DISCUSSION: Our study revealed that
      public school adolescents are characterized by males with higher self-esteem and
      less attitude for HIV/AIDS, while in private school the males has more peer
      pressure and seeking sensation than females. Future studies could analyze factors
      related with changes in developmental factors, this step is important to evaluate
      the effectiveness of ASUMA interventions.

PMID- 23875521
TI  - Variation of the posterior cerebral artery and its embryological explanation: a
      cadaveric study.
AB  - The posterior cerebral arteries are paired vessels that usually originate from
      the basilar artery at the level of the pontomesencephalic fissure and are joined
      by the posterior communicating artery to close the posterior portion of the
      Circle of Willis (circulus arteriosus cerebri). There is a considerable variation
      in the presence of the arterial segments of the circle of Willis. In the fetal
      type posterior cerebral artery there is an embryonic derivation of this vessel
      from the internal carotid artery. The irrigation of the posterior cerebral artery
      territory is thus completely dependent on the internal carotid artery. The term
      fetal-type posterior cerebral artery is used whether or not there is a
      communication with the basilar artery through a small pre-communicating segment
      (P1) of the posterior cerebral artery. This study deals with the variations of
      the posterior part of the circle of Willis, especially the origin of the
      posterior cerebral artery (PCA). The size of the posterior communicating artery
      (PComA) in comparison with the size of posterior cerebral artery is one of the
      principal differences between the fetal and adult forms of the circulus
      arteriosus cerebri. There are three configurations regarding posterior cerebral
      and posterior communicating arteries according to compare their diameters.

PMID- 23875520
TI  - Changes in the socio-demographics, risk behaviors, clinical and immunological
      profile of a cohort of the Puerto Rican population living with HIV: an update of
      the Retrovirus Research Center (1992-2008).
AB  - OBJECTIVES: We describe the changes in the socio demographic, risk behavior,
      immunological and clinical trends profiles of a cohort HIV patients followed at
      the Retrovirus Research Center, at baseline and study periods interval by periods
      intervals: 1992-1997, 1998-2003, and 2004-2008. METHODS: This is a cross
      sectional study of a longitudinal cohort comprised of 4016 HIV/AIDS patients
      admitted to the RRC since January 1992. Data collected include socio-demographic
      variables; risk related variables; psychological variables; and clinical variable
      by periods of study. RESULTS. The most common AIDS defining conditions observed
      in patients were: Pneumocistis Cariini pneumonia (PCP), toxoplasmosis of brain
      (TP), and wasting syndrome (WS). Chronic conditions are more prevalent than AIDS
      defining conditions in the cohort of patients. CONCLUSIONS: Understanding the
      socio demographic, HIV risk behavior profile; and the immunological and clinical
      trends among HIV patients is critical for redesigning services and programs
      oriented in HIV patient care.

PMID- 23875522
TI  - Clinical studies support a role for trem-like transcript-1 during the progression
      of sepsis.
AB  - Sepsis is a multi-factorial disease that kills an estimated 1,400 people a day
      worldwide. The Triggering Receptor Expressed in Myeloid (TREM) cells Like
      Transcript (TLT)-1 is a platelet receptor expressed on activated platelets.
      Translational studies of TLT-1 suggest that TLT-1 affects hemostatic and
      immunological parameters that lead to the formation of disseminated intravascular
      coagulation (DIC). Evaluation of mice suffering from endotoxic shock shows a
      dramatic increase of soluble TLT-1 (sTLT-1) in their blood. Accordingly, when we
      evaluated the blood of septic patients we find increased levels of sTLT-1 that
      correlate with the presence of DIC in humans. Based on current data we
      hypothesize that TLT-1 plays an important role in maintaining vascular integrity
      during sepsis; perhaps by modulation of both the immune and hemostatic systems,
      and that TLT-1 makes an attractive target not only for better understanding of
      sepsis, but also as a point of therapeutic intervention as well.

PMID- 23875523
TI  - Failure to pass meconium.
AB  - Failure to pass meconium during the first twenty-hours of life is a cardinal sign
      of a congenital low alimentary tract obstruction. This review article discusses a
      systematic approach when confronting such problem to help clinicians arrive to a
      correct diagnosis. Prenatal and postnatal diagnosis, imaging investigation,
      differential diagnosis and management of the more common causes of failure to
      pass meconium are reviewed.

PMID- 23875524
TI  - Late presentation of familial mediterranean fever: a case report.
AB  - Familial Mediterranean Fever (FMF) is an autosomal recessive disorder
      predominantly affecting people of Mediterranean origin. It is characterized by
      recurrent episodes of fever and polyserositis of unexplained origin. Most
      patients with FMF experience their first attack in early childhood with 90%
      suffering their first bout of pain by the age of 20. We present a case of a 68
      years old woman who presented with fevers of 9 months of evolution which
      culminated with a diagnosis of Familial Mediterranean Fever after successful
      treatment with Colchicine.

PMID- 23875525
TI  - Rectal stricture: a rare presentation of primary amyloidosis.
AB  - Amyloidosis is a process were an abnormal protein deposits in tissues. This
      deposit accumulates and may eventually cause a variety of nonspecific symptoms.
      Primary amyloidosis refers to amyloidosis caused by an underlying plasma cell
      disorder. Protein electrophoresis showing a monoclonal band is suggestive of the
      disease but in order to make the diagnosis, the presence of amyloid deposition on
      tissues must be shown by biopsy. We present a woman in whom primary amyloid is
      manifested as a rectal stricture. She came to the gastroenterology clinics
      complaining of hematochezia, weight loss, decreased appetite and abdominal pain.
      Her only sign of organ damage was mild to moderate proteinuria (80mg per day).
      The patient also had an unusual retroperitoneal infiltration with encasement of
      the abdominal aorta.

PMID- 23875526
TI  - Development of Grave's disease seven months after Hashimoto's thyroiditis: a rare
      occurrence.
AB  - Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two opposite poles in
      the spectrum of autoimmune thyroid disease. On one extreme, HT or Chronic
      Lymphocytic thyroiditis (CLT) courses, as its name implies, with lymphocytic
      infiltrates replacing thyroid follicles, resulting in a loss of hormone-producing
      cells and, thus, primary hypothyroidism. On the other extreme, GD is
      characterized by primary hyperthyroidism due to stimulating autoantibodies
      against thyroid-stimulating hormone receptors (TSHRs) localized on thyrocytes'
      membranes of intact thyroid follicles. The presence of HT after GD or the
      concomitant combination of these two autoimmune entities ending in HT-depending
      hypothyroid state is well known. However, occurrence of GD after primary
      hypothyroidism due to CLT is very rare since thyrocytes with their TSHRs are
      promptly lost. We report a case in which hyperthyroidism occurred seven months
      after presentation of primary hypothyroidism and discuss potential mechanisms
      involved.

PMID- 23875527
TI  - Hidden in plain sight: macrophage activation syndrome complicating Adult Onset
      Still's Disease.
AB  - Hemophagocytic Lymphystiocytosis is a rare and fatal complication of rheumatic
      diseases, particularly Adult Onset Still's Disease (AOSD). It may be precipitated
      with immunosuppressive drugs and with viral and bacterial infections. A diagnosis
      depends on a high index of suspicion associated to certain clinical
      manifestations (fever, rash, Splemomegaly, any cytology blood dyscrasia,
      hipertrigliceridemia, hiperfibrinogenemia, and others), as well as pathologic
      evidence of hemophagocitosis from bone marrow biopsy or tissue samples of
      affected organs. Therapy consists of high dose corticosteroids and
      immunosuppressive drugs. We present a 42 year old woman with AOSD in remission
      who developed HLH in spite of receiving therapy with high dose steroids and
      immunosuppressive drugs. She had 2 negative bone marrow aspirates. Evidence of
      Hemophagocytosis was detected in both bone marrow biopsies. Timely evaluation and
      recognition of the signs and symptoms of HLH is crucial for the prompt management
      and a decrease in the mortality associated with this disease.

PMID- 23875528
TI  - Acute hepatitis A infection: a predisposing factor for severe leptospirosis.
AB  - Leptospirosis is a rare and potentially fatal infection that requires a high
      index of suspicion for timely diagnosis and treatment. Diagnosis of leptospirosis
      can be particularly difficult in context of coexistent viral hepatitis. We
      present a case of Weil's syndrome, in which a concurrent resolving Hepatitis A
      virus infection was concomitantly diagnosed. Assessment of epidemiologic risk
      factors and serial serology testing were key in making this diagnosis. The
      immunologic consequence of the coexistence of these two infections is also
      discussed. It is likely that hepatitis A infection predisposed our patient's
      leptospirosis infection to progress to Weil's syndrome.

PMID- 23875529
TI  - Virus-mimicking optical nanomaterials: near infrared absorption and fluorescence
      characteristics and physical stability in biological environments.
AB  - The use of viruses as platforms for the development of optical imaging materials
      has received increasing attention in recent years. We have engineered a hybrid
      nanomaterial composed of the capsid proteins of genome-depleted plant-infecting
      Brome mosaic virus that encapsulates the near-infrared (NIR) dye indocyanine
      green. Herein, we investigate the NIR absorption and fluorescence characteristics
      of these nanomaterials in biological environments consisting of cell culture
      media with and without serum proteins. Our results demonstrate that the NIR
      absorption and fluorescence emission of the constructs are enhanced in the
      presence of serum proteins. The constructs remain physically stable and maintain
      their NIR absorption and fluorescence properties for at least 79 days. The
      presence of serum proteins also reduces the aggregation of the constructs. These
      findings have relevance for the further development of optical imaging and
      phototherapeutic methods on the basis of such virus-mimicking nanomaterials as
      well as the expected optical and physical characteristics of these nanomaterials
      in vivo. 

PMID- 23875530
TI  - Active change detection by pigeons and humans.
AB  - Detecting change is vital to both human and nonhuman animals' interactions with
      the environment. Using the go/no-go dynamic change detection task, we examined
      the capacity of four pigeons to detect changes in brightness of an area on a
      computer display. In contrast to our prior research, we reversed the response
      contingencies so that the animals had to actively inhibit pecking upon detecting
      change in brightness rather than its constancy. Testing eight rates of change
      revealed that this direct report change detection contingency produced results
      equivalent to the earlier indirect procedure. Corresponding tests with humans
      suggested that the temporal dynamics of detecting change were similar for both
      species. The results indicate the mechanisms of change detection in both pigeons
      and humans are organized in similar ways, although limitations in the operations
      of working memory may prevent pigeons from integrating information over the same
      time scale as humans.

PMID- 23875531
TI  - Competitive interactions of ionic surfactants with salbutamol and bovine serum
      albumin: a molecular spectroscopy study with implications for salbutamol in food
      analysis.
AB  - The effect of ionic surfactants, sodium dodecyl sulfate (SDS) and N-cetyl-N,N,N
      trimethylammonium bromide (CTAB), on the interaction between beta-agonist
      salbutamol (SAL) and bovine serum albumin (BSA) was investigated with the use of
      fluorescence spectroscopy (FLS) and chemometrics methods [multivariate curve
      resolution-alternating least-squares (MCR-ALS) and parallel factor analysis
      algorithm (PARAFAC)]. It was found that the binding constant of SAL to BSA in the
      presence of CTAB was much larger than that without this ligand. The ligand/BSA
      stoichiometry was 4:1, that is, (CTAB)4-BSA, and was 2:1 with the ligand, that
      is, (SAL)2-BSA. These results were obtained from the concentration profiles
      extracted by MCR-ALS for all three reactants. Quantitative information on the
      complex CTAB-BSA-SAL species was obtained with the resolution of the excitation
      emission fluorescence three-way data matrices by PARAFAC. This research has
      implications for the analysis of SAL in food and might be performed in
      laboratories associated with organizations such as the U.S. Food and Drug
      Administration (FDA) and the International Olympic Committee (IOC). 

PMID- 23875532
TI  - Sexual lives of women with diabetes mellitus (type 2) and impact of culture on
      solution for problems related to sexual life.
AB  - AIMS AND OBJECTIVES: To examine sexual lives of women with diabetes mellitus
      (type 2) (DM) and impact of culture on solution for problems related to sexual
      life. BACKGROUND: DM has long been considered a risk factor for sexual
      dysfunction in men and women, although the evidence in women is less clear. This
      study was conducted to emphasise the effect of DM and culture on sexual life.
      DESIGN: A descriptive and qualitative study. METHODS: Planned as descriptive and
      qualitative, this study was conducted with 38 women who matched with the
      following inclusion criterion: living in a neighbourhood with low socio-economic
      status in the province of Kayseri, Turkey. The Participant Information Form,
      Diabetes Control Form, the Arizona Sexual Experiences Scale (ASEX), Sexual Life
      Definition Form and Semi-Structured Interview Form for revealing problems lived
      in sexual life, besides the results of laboratory tests, were used for data
      collection. RESULTS: Mean age of the participating women was 51.34 +/- 5.85
      years. Total score of ASEX was found to be correlated with the type of DM
      treatment, duration of DM diagnosis, complications of DM, relation with her
      husband, level of HbA1c and systolic-diastolic blood pressure (p < 0.05). Of the
      participating women, 47.4% expressed that they had problems with sexual relation.
      CONCLUSION: Most of the women with DM were determined to have problems in sexual
      functions besides the disease, and the impact of culture on the solution for
      problems lived within sexual life was effective. RELEVANCE TO CLINICAL PRACTICE:
      These findings can help guide to raise the health of Turkish women with diabetes
      and to plan appropriate nursing interventions.

PMID- 23875533
TI  - In vivo fluorescent adenosine 5'-triphosphate (ATP) imaging of Drosophila
      melanogaster and Caenorhabditis elegans by using a genetically encoded
      fluorescent ATP biosensor optimized for low temperatures.
AB  - Adenosine 5'-triphosphate (ATP) is the major energy currency of all living
      organisms. Despite its important functions, the spatiotemporal dynamics of ATP
      levels inside living multicellular organisms is unclear. In this study, we
      modified the genetically encoded Forster resonance energy transfer (FRET)-based
      ATP biosensor ATeam to optimize its affinity at low temperatures. This new
      biosensor, AT1.03NL, detected ATP changes inside Drosophila S2 cells more
      sensitively than the original biosensor did, at 25  degrees C. By expressing
      AT1.03NL in Drosophila melanogaster and Caenorhabditis elegans, we succeeded in
      imaging the in vivo ATP dynamics of these model animals at single-cell
      resolution. 

PMID- 23875534
TI  - Photoreconfigurable supramolecular nanotube.
AB  - A photoreconfigurable bionanotube was developed by Mg(2+)-induced supramolecular
      polymerization using GroELSP, a mutant barrel-shaped chaperonin protein bearing
      multiple photochromic spiropyran (SP) units at its apical domains. Upon exposure
      to UV light, the nonionic SP units isomerize into ionic merocyanine (MC) to
      afford GroELMC, which is capable of polymerizing with MgCl2. The resultant
      nanotube (NT) is stable as a result of multiple MC...Mg(2+)...MC bridges but
      readily breaks up into short NTs, including monomeric GroELSP, by the reverse (MC
      -> SP) isomerization mediated by visible light. When this scission mixture is
      exposed to UV light, long NTs are reconfigured. A Forster resonance energy
      transfer (FRET) study revealed that NTs in the dark maintain their sequential
      integrity. However, when exposed to visible and UV light successively, the NTs
      lose their sequential memory as a result of intertubular reshuffling of the
      constituent GroELMC units. 

PMID- 23875535
TI  - Size selective incorporation of gold nanoparticles in diblock copolymer vesicle
      wall.
AB  - A systematic study is conducted to reveal how far the polymeric vesicle wall can
      embed gold nanoparticles (AuNPs) with different sizes by combining experiments
      and self-consistent field simulations. Both the experimental and simulative
      results indicate that the location of AuNPs in vesicle wall or in spherical
      micelle is heavily size dependent. Whether the AuNPs enter the vesicle wall or
      not is determined by a ratio of the diameter of AuNPs (D0) to the thickness of
      the vesicle wall (d(w0)). The 1-dodecanethiol-coated AuNPs (Au(x)R) with D0/d(w0)
      < 0.3 will stably disperse in the vesicle walls. For polystyrene-coated AuNPs
      (Au(x)S), a criterion of D0/d(w0) is proposed based on the phase diagram; i.e.,
      the Au(x)S with D0/d(w0) < 0.5 can be located in the vesicle wall. Otherwise, the
      Au(x)R and the Au(x)S prefer to locate in spherical micelles. Moreover, the
      contributions of enthalpy and entropy to the total free energy of the system are
      respectively calculated to reveal the mechanism of the size selective
      distribution of AuNPs. The results demonstrate that the escape of AuNPs from
      vesicle walls and their selective distribution in spherical micelles is an
      entropy-driven process. Our study provides an important guideline for fabricating
      nanoparticle/block copolymer hybrid vesicles in dilute solution.

PMID- 23875537
TI  - Biologic fatigue in psoriasis.
AB  - BACKGROUND: Over the past 15 years, biologic medications have greatly advanced
      psoriasis therapy. However, these medications may lose their efficacy after long
      term use, a concept known as biologic fatigue. We sought to review the available
      data on biologic fatigue in psoriasis and identify strategies to help clinicians
      optimally manage patients on biologic medications in order to minimize biologic
      fatigue. METHODS: We reviewed phase III clinical trials for the biologic
      medications used to treat psoriasis and performed a PubMed search for the
      literature that assessed the loss of response to biologic therapy. RESULTS: In
      phase III clinical trials of biologic therapies for the treatment of psoriasis,
      20-32% of patients lost their PASI-75 response during 0.8-3.9 years of follow-up.
      A study using infliximab reported the highest percentage of patients who lost
      their response (32%) over the shortest time-period (0.8 years). Although not
      consistently reported across all studies, the presence of antidrug antibodies was
      associated with the loss of response to treatment with infliximab and adalimumab.
      CONCLUSION: Biologic fatigue may be most frequent in those patients using
      infliximab. Further studies are needed to identify risk factors associated with
      biologic fatigue and to develop meaningful antidrug antibody assays.

PMID- 23875538
TI  - The Worringham and Beringer 'visual field' principle for rotary controls.
AB  - Worringham and Beringer (1989, 1998) developed a very important principle
      relating compatibility of movement of horizontally moving translational controls
      to display movements when the operator's view of the display is in a plane
      different to that of the control. On the basis of past data of the current
      authors, it is shown that the visual field principle also applies to the
      operation of vertically moving translational controls and to rotary controls.
      These additions make the Worringham and Beringer principle the most powerful
      design principle available for situations where the operator is viewing a display
      that is not in the same plane as the control. PRACTITIONER SUMMARY: High
      compatibility between control input and display output is of great importance in
      machine design. This paper demonstrates that, for cases where the display is not
      in the same plane as the control, the visual field principle is operational for
      vertically moving translational controls and rotary controls as well as for
      horizontally moving translational controls.

PMID- 23875539
TI  - HIV status disclosure to families for social support in South Africa (NIMH
      Project Accept/HPTN 043).
AB  - Literature on HIV status disclosure among persons living with HIV/AIDS (PLWHA) is
      dominated by research on the rates, barriers and consequences of disclosure to
      sexual partners, because of the assumed preventive health benefits of partner
      disclosure. Disclosure of HIV status can lead to an increase in social support
      and other positive psychosocial outcomes for PLWHA, but disclosure can also be
      associated with negative social outcomes including stigma, discrimination, and
      violence. The purpose of this article is to describe the HIV status disclosure
      narratives of PLWHA living in South Africa. Thirty in-depth interviews were
      conducted with 13 PLWHA (11 women, 2 men) over a three-year period. We explored
      disclosure narratives of the PLWHA through questions about who they chose to
      disclose to, how they disclosed to these individuals, and how these individuals
      reacted. Narratives focused on disclosure to family members and contained
      relatively little discussion of disclosure to sexual partners. Participants often
      disclosed first to one trusted family member, and news of the diagnosis remained
      with this person for a long period of time, prior to sharing with others. This
      family member helped the PLWHA cope with the news of their diagnosis and prepared
      them to disclose to others. Disclosure to one's partner was motivated primarily
      by a desire to encourage partners to test for HIV. Two participants described
      overtly negative reactions from a partner upon disclosure, and none of the PLWHA
      in this sample described very supportive relationships with their partners after
      disclosure. The critical role that family members played in the narratives of
      these PLWHA emphasizes the need for a greater focus on disclosure to families for
      social support in HIV counseling protocols. 

PMID- 23875536
TI  - SISH/CISH or qPCR as alternative techniques to FISH for determination of HER2
      amplification status on breast tumors core needle biopsies: a multicenter
      experience based on 840 cases.
AB  - BACKGROUND: Until now, FISH has been the gold standard technique to identify HER2
      amplification status in ambiguous cases of breast cancer. Alternative techniques
      have been developed to increase the capacities of investigating HER2
      amplification status. The aims of this multicenter study in a large series of
      breast cancer patients were to prospectively compare the level of performance of
      CISH, SISH, and qPCR alternative techniques on paraffin-embedded core biopsies
      with "gold standard FISH" for evaluation of HER2 amplification status. METHODS:
      This study was performed on 840 cases scored by immunohistochemistry (IHC): 0=317
      (38%), 1+=183 (22%), 2+=109 (13%), 3+=231 (27%). Each of the 15 French centers
      participating in the study analyzed 56 breast carcinoma cases diagnosed on fixed
      paraffin-embedded core biopsies. HER2 amplification status was determined by
      commercially available FISH used as the reference technique with determination of
      the HER2/CEN17 ratio or HER2 copy number status. The alternative techniques
      performed on the same cases were commercially available SISH or CISH and a common
      qPCR method especially designed for the study including a set of 10 primer pairs:
      2 for HER2 (exons 8 and 26), 5 to evaluate chromosome 17 polysomy TAOK1, UTP6,
      MRM1, MKS1, SSTR2 and 3 for diploidy control TSN, LAP3 and ADAMTS16. RESULTS: The
      concordance between IHC and FISH was 96% to 95% based on the HER2/CEN17 ratio
      (n=766) or HER2 copy number (n=840), respectively. The concordance of the
      alternative techniques with FISH was excellent: 97% and 98% for SISH (498 and 587
      cases), 98% and 75% for CISH (108 and 204 cases) and 95% and 93% (699 and 773
      cases) for qPCR based on the HER2/CEN17 ratio or HER2 copy number, respectively.
      Similarly, sensitivity ranged from 99% to 95% for SISH, 100% to 99% for CISH and
      89% to 80% for qPCR. The concordance with FISH (ratio) in the 2+ cases was 89%
      for SISH, 100% for CISH and 93% for qPCR. CONCLUSION: These alternative
      techniques showed an excellent concordance with FISH in core biopsies allowing
      their use in routine clinical practice. This newly designed qPCR on paraffin
      embedded core biopsies deserves special attention, as it is reliable, easy to
      perform and less expensive than ISH tests.

PMID- 23875540
TI  - Association of ADRB2 polymorphism with triglyceride levels in Tongans.
AB  - BACKGROUND: Our previous study demonstrated that the A-allele of the single
      nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the
      beta2 adrenergic receptor gene (ADRB2) is significantly associated with risk for
      obesity in Oceanic populations. METHODS: To investigate whether the ADRB2
      polymorphisms explain part of the individual differences in lipid mobilization,
      energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with
      total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol and triglyceride levels were examined in 128 adults in Tonga.
      RESULTS: A multiple linear regression analysis adjusted for age, sex, and body
      mass index revealed that rs34623097 was significantly associated with
      triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele
      increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the
      ADRB2 SNPs showed a significant association with total-cholesterol, high-density
      lipoprotein cholesterol, or low-density lipoprotein cholesterol. CONCLUSIONS: In
      a Tongan population, a SNP located in the upstream region of ADRB2 is associated
      with triglyceride levels independent of body mass index.

PMID- 23875541
TI  - BMI but not stage or etiology of nonalcoholic liver disease affects the
      diagnostic utility of carbohydrate-deficient transferrin.
AB  - BACKGROUND: A reliable biomarker is required in hepatology clinics for detection
      and follow-up of heavy alcohol consumption. Carbohydrate-deficient transferrin
      (CDT) increases with sustained heavy alcohol consumption and is the most specific
      biomarker of ethanol (EtOH) consumption. Recent introduction of a standardized
      method for measuring CDT has improved its clinical application. This study was
      designed to determine whether alcohol-independent factors influence CDT levels in
      patients with chronic liver disease (CLD). METHODS: The relationship between
      serum %CDT and self-reported history of alcohol consumption was examined in 254
      patients referred for evaluation of liver disease. CDT analysis was performed on
      serum collected at time of liver biopsy. RESULTS: CDT levels were not affected by
      severity or etiology of nonalcoholic liver disease. Thirteen of 254 subjects had
      a %CDT >1.7, predictive of heavy alcohol intake, 6 of whom did not acknowledge
      heavy drinking. Twelve of these 13 subjects were suspected heavy drinkers on
      review of their medical records and clinical results. Conversely, not all
      acknowledged heavy drinkers had %CDT >1.7. Heavy drinkers with a body mass index
      (BMI) in the overweight or obese range had significantly lower %CDT than lean
      heavy drinkers. This persisted even when lean body weight was used as an
      approximation of the EtOH volume of distribution. CONCLUSIONS: An elevated BMI
      reduces the diagnostic utility of CDT at higher alcohol intake in subjects with
      CLD using the standardized method. In a hepatology outpatient setting, this assay
      is likely to be useful to confirm suspicion of heavy drinking in subjects who are
      not overweight, but cannot reliably identify moderate drinkers or heavy drinkers
      who are overweight.

PMID- 23875542
TI  - Isolation and structure elucidation of satosporin A and B: new polyketides from
      Kitasatospora griseola.
AB  - Satosporins A and B, two novel glucosylated polyketides, were isolated from the
      actinomycete Kitasatospora griseola MF730-N6. The polyketides possess an
      unprecedented tricyclic ring system that was fully characterized using a
      combination of spectroscopic analyses and computational calculations. Satosporin
      A was quantitatively converted into its aglycon homologue, satosporin C, using a
      beta-glucosidase. The determination of the absolute stereochemistry was achieved
      using solution TDDFT/ECD calculations and chemical derivatization methods. 

PMID- 23875543
TI  - Floppy eyelid associated with Down syndrome.
AB  - Eyelid laxity due to Down Syndrome may be better classified under the rubric of
      lax eyelid conditions.

PMID- 23875544
TI  - In vitro evaluation of defined oligosaccharide fractions in an equine model of
      inflammation.
AB  - BACKGROUND: Dietary supplementation with oligosaccharides has been proven to be
      beneficial for health in several mammalian species. Next to prebiotic effects
      resulting in a modulation of gut micro biota, immunomodulatory effects of
      oligosaccharides have been documented in vivo. Supplementation with defined
      oligosaccharide fractions has been shown to attenuate allergic responses and
      enhance defensive immune responses. Despite the accumulating evidence for
      immunomodulatory effects, very limited information is available regarding the
      direct mechanism of action of oligosaccharides. This study aims to elucidate the
      effects of selected oligosaccharide fractions on the lipopolysaccharide (LPS)
      induced inflammatory response in equine peripheral blood mononuclear cells
      (PBMCs). We investigated three different products containing either galacto
      oligosaccharides (GOS) alone, a combination of GOS with fructo-oligosaccharides
      (FOS), and a triple combination of GOS and FOS with acidic oligosaccharides
      (AOS), at different concentrations. These products have been used in an identical
      composition in various previously published in vivo experiments. As the selected
      oligosaccharide fractions were derived from natural products, the fractions
      contained defined amounts of mono- and disaccharides and minor amounts of
      endotoxin, which was taken into account in the design of the study and the
      analysis of data. Acquired data were analysed in a Bayesian hierarchical linear
      regression model, accounting for variation between horses. RESULTS: Exposing
      cultured PBMCs to either GOS or GOS/FOS fractions resulted in a substantial dose
      dependent increase of tumour necrosis factor-alpha (TNF-alpha) production in LPS
      challenged PBMCs. In contrast, incubation with GOS/FOS/AOS resulted in a dose
      dependent reduction of both TNF-alpha and interleukin-10 production following LPS
      challenge. In addition, incubation with GOS/FOS/AOS significantly increased the
      apparent PBMC viability, indicating a protective or mitogenic effect.
      Furthermore, mono- and disaccharide control fractions significantly stimulated
      the inflammatory response in LPS challenged PBMCs as well, though to a lesser
      extent than GOS and GOS/FOS fractions. CONCLUSIONS: We found distinct
      immunomodulating effects of the investigated standardised oligosaccharide
      fractions, which either stimulated or suppressed the LPS induced inflammatory
      response in PBMCs. Both scenarios require additional investigation, to elucidate
      underlying modulatory mechanisms, and to translate this knowledge into the
      clinical application of oligosaccharide supplements in foals and other neonates.

PMID- 23875545
TI  - Intersectional perspectives on family involvement in nursing home care:
      rethinking relatives' position as a betweenship.
AB  - This study seeks to understand, in the context of intersectional theory, the
      roles of family members in nursing home care. The unique social locus at which
      each person sits is the result of the intersection of gender, status, ethnicity
      and class; it is situational, shifting with the context of every encounter. A
      content analysis of 15 qualitative interviews with relatives of nursing home
      residents in Sweden was used to gain a perspective on the relationships between
      relatives and residents, relatives and the nursing home as an institution, and
      relatives and the nursing home staff. We sought to understand these relationships
      in terms of gendered notions of the family and the residents, which are handed
      down from generation to generation and thus condition who and how relatives
      should be involved in care, and the ways in which relationships change as care
      moves from home to nursing home. It requires knowledge and awareness that the
      nursing home culture is based on intersectional power structures in order for
      relatives to be involved in nursing home care in alternative and individual ways.

PMID- 23875546
TI  - Excess mortality during hospital stays among patients with recorded diabetes
      compared with those without diabetes.
AB  - AIM: To assess the additional mortality during hospital admissions among patients
      with recorded diabetes and identify the extent of variation in English provider
      trusts. METHODS: Inpatient admissions to all English hospitals between April 2010
      and March 2012 were extracted from Hospital Episode Statistics. Binary logistic
      regression was used to standardize for age, sex, deprivation, method and reason
      for admission, co-morbidities and type of trust. Trust level standardized
      mortality ratios for inpatients with recorded diabetes were compared with those
      without recorded diabetes and with published measures of hospital mortality.
      RESULTS: Of the 10 169 003 hospital admissions analysed, 11.2% had recorded
      diabetes, but 21.5% of inpatient deaths occurred in this group. After adjustment
      for case mix, hospital admissions in patients with recorded diabetes had a 6.4%
      greater risk of dying (2052 more deaths over 2 years) than would be expected
      compared with similar patients without recorded diabetes. The additional risk of
      death was significantly greater in smaller trusts. The highest additional risk of
      death was found in hospital admissions of younger female patients admitted
      electively. At provider trust level, 37.4% of variation in adjusted mortality in
      patients with recorded diabetes was explained by the mortality in those without
      recorded diabetes. CONCLUSION: A diagnosis of diabetes has an adverse impact on
      hospital mortality that cannot be explained by usual case-mix adjustments, and
      the additional risk of dying is greatest among hospital admissions that would
      normally have a low risk of death. This implies that diabetes may override the
      usual risk factors for hospital mortality.

PMID- 23875548
TI  - Highlights of the International Society of Psychiatric-Mental Health Nurses
      annual meeting.

PMID- 23875547
TI  - Stage-specific transcription during development of Aedes aegypti.
AB  - BACKGROUND: Aedes aegypti is the most important global vector of dengue virus
      infection in humans. Availability of the draft genome sequence of this mosquito
      provides unique opportunities to study different aspects of its biology,
      including identification of genes and pathways relevant to the developmental
      processes associated with transition across individual life stages. However,
      detailed knowledge of gene expression patterns pertaining to developmental stages
      of A. aegypti is largely lacking. RESULTS: We performed custom cDNA microarray
      analyses to examine the expression patterns among six developmental stages: early
      larvae, late larvae, early pupae, late pupae, and adult male and female
      mosquitoes. Results revealed 1,551 differentially expressed transcripts (DETs)
      showing significant differences in levels of expression between these life
      stages. The data suggests that most of the differential expression occurs in a
      stage specific manner in A. aegypti. Based on hierarchical clustering of
      expression levels, correlated expression patterns of DETs were also observed
      among developmental stages. Weighted gene correlation network analysis revealed
      modular patterns of expression among the DETs. We observed that hydrolase
      activity, membrane, integral to membrane, DNA binding, translation, ribosome,
      nucleoside-triphosphatase activity, structural constituent of ribosome,
      ribonucleoprotein complex and receptor activity were among the top ten ranked GO
      (Gene Ontology) terms associated with DETs. Significant associations of DETs were
      also observed with specific KEGG (Kyoto Encyclopedia of Genes and Genomes)
      pathway modules. Finally, comparisons with the previously reported developmental
      transcriptome of the malaria vector, Anopheles gambiae, indicated that gene
      expression patterns during developmental processes reflect both species-specific
      as well as common components of the two mosquito species. CONCLUSIONS: Our study
      shows that genes involved in the developmental life cycle of A. aegypti are
      expressed in a highly stage-specific manner. This suggests that transcriptional
      events associated with transition through larval, pupal and adult stages are
      largely discrete.

PMID- 23875549
TI  - Female survivors of child sexual abuse: finding voice through research
      participation.
AB  - It is unclear whether survivors of trauma are at risk of emotional or
      psychological distress when they participate in research because there is little
      data on the subjective experience of research study participants and how they
      make meaning from their participation in research. This qualitative descriptive
      study explored the experience of research participation by survivors of childhood
      sexual abuse. We interviewed 12 female survivors and identified themes.
      Participants noted both positive personal and societal benefits of study
      participation and reported no harm due to their research participation. Study
      findings can help researchers understand the perspectives of participants
      regarding the benefits of taking part in violence research and can help allay
      concerns over causing participants undue psychological distress. 

PMID- 23875550
TI  - Staff's experiences of a person-centered health education group intervention for
      people with a persistent mental illness.
AB  - Patient education in mental health care is a conventional intervention to
      increase patients' knowledge about their illness and treatment. A provider
      centered focus in patient education may put patients in a passive role, which can
      counteract their processes of recovery. There is an increasing emphasis on
      recovery-oriented practice, an approach that is aligned with the service user
      perspective, but little is known about health care staff's perspectives on person
      centered mental health care. A qualitative approach was used to describe staff's
      experiences of being group leaders in a person-centered health education
      intervention in municipal services for persons with a persistent mental illness.
      The analysis of staff experiences revealed three core categories: (1)
      implications of the division of responsibility among local authorities, (2)
      awareness of facilitating factors of growth, and (3) the meaning of dialogue.
      These formed the theme Preconditions for Person-Centered Care. Further research
      is required to explore larger economic, political, and social structures as
      backdrops to person-centered mental health care, from the perspective of service
      users, families, health professionals, and the community at large. 

PMID- 23875551
TI  - Evaluation of a brief cognitive behavioral group therapy for psychological
      distress among female Icelandic University students.
AB  - A study of a brief cognitive behavioral group therapy intervention for
      psychologically distressed Icelandic female university students was conducted
      using a pre-post test quasi-experimental design with intervention and control
      group conditions. Students were randomly allocated to control and intervention
      group conditions (n = 30). The intervention group received four sessions of
      cognitive behavioral group therapy, delivered by two advanced practice
      psychiatric nurses. Assessment of distress included self-reported depression and
      anxiety symptoms. Students in the intervention group experienced significantly
      lower levels of depression and anxiety symptoms compared to the control group
      post-test providing preliminary evidence concerning intervention effectiveness
      for Icelandic students. 

PMID- 23875552
TI  - Self-silencing as a predictor of physical activity behavior.
AB  - Self-silencing theory suggests that women ignore their own feelings and needs to
      attend to the desires of others. However, the impact of such self-silencing on
      physical activity behavior is unknown. This study examined the degree of self
      silencing among a group of highly educated and relatively affluent African
      American women and the strength of self-silencing as a predictor of physical
      activity. The mean total self-silencing score for participants was 71.46.
      Overall, women reported spending approximately 193 min per week engaged in
      physical activity but only 36% met current recommendations for aerobic physical
      activity. Self-silencing did not predict physical activity behavior.

PMID- 23875553
TI  - Identification of the "minimal triangle" and other common event-to-event
      transitions in conflict and containment incidents.
AB  - Although individual conflict and containment events among acute psychiatric
      inpatients have been studied in some detail, the relationship of these events to
      each other has not. In particular, little is known about the temporal order of
      events for individual patients. This study aimed to identify the most common
      pathways from event to event. A sample of 522 patients was recruited from 84
      acute psychiatric wards in 31 hospital locations in London and the surrounding
      areas during 2009-2010. Data on the order of conflict and containment events were
      collected for the first two weeks of admission from patients' case notes. Event
      to-event transitions were tabulated and depicted diagrammatically. Event types
      were tested for their most common temporal placing in sequences of events. Most
      conflict and containment occurs within and between events of the minimal triangle
      (verbal aggression, de-escalation, and PRN medication), and the majority of these
      event sequences conclude in no further events; a minority transition to other,
      more severe, events. Verbal abuse and medication refusal were more likely to
      start sequences of disturbed behaviour. Training in the prevention and management
      of violence needs to acknowledge that a gradual escalation of patient behaviour
      does not always occur. Verbal aggression is a critical initiator of conflict
      events, and requires more detailed and sustained research on optimal management
      and prevention strategies. Similar research is required into medication refusal
      by inpatients. 

PMID- 23875554
TI  - Quality of life determinants in patients of a Psychosocial Care Center for
      alcohol and other drug users.
AB  - Quality of life assessments in patients receiving treatment for substance
      dependence can serve as one predictor of response to treatment. This study aimed
      to identify determinants of quality of life in patients of a Psychosocial Care
      Center for alcohol and other drug users (CAPSad). The sample consisted of 77
      patients with a diagnosis of substance dependence being treated at CAPSad for
      more than six months. Severity of substance dependence was assessed using the
      Addiction Severity Index (ASI-6), quality of life was assessed using the World
      Health Organization Quality of Life assessment instrument-short version (WHOQOL
      BREF), and depressive symptoms were assessed by the Beck Depression Inventory
      (BDI). Data on CAPSad activities, psychiatric diagnoses, and medications used
      were collected from the medical records. Quality of life was significantly
      impaired in more severe cases of substance dependence and in those with more
      severe depressive symptoms. As for other variables, poorer quality of life was
      significantly associated with a greater number of years of education,
      unemployment, use of medications, and greater use of individual sessions with the
      reference professional. Linear regression analysis revealed depressive symptom
      severity to be an independent determinant of quality of life impairment,
      accounting for over 50% of the variation in physical and psychological domains.
      These results demonstrate the need to consider other factors, such as depressive
      symptoms and quality of life, in the treatment of substance dependence. 

PMID- 23875555
TI  - Is cardiovascular or resistance exercise better to treat patients with
      depression? A narrative review.
AB  - OBJECTIVES: There is growing evidence regarding the efficacy of exercise as a
      treatment strategy for patients with depression. This paper summarises the
      benefits of both cardiovascular and resistance exercise for patients with
      depression. DESIGN: A narrative review design was employed. Supporting literature
      for the individual and combined benefits of both modalities are presented.
      Studies comparing both modalities are then discussed. RESULTS: The outcomes of
      the review indicate that there is evidence for the efficacy of both
      cardiovascular exercise and resistance exercise, either independently or
      combined, in the treatment of depression across the range of severity levels and
      age groups. CONCLUSION: Exercise interventions for the treatment of depression
      appear worthwhile and well tolerated. Exercise preference, access to resources
      and social support may shape the choice for the patient. The role of primary and
      allied health professionals in guiding this choice is discussed. Implications for
      clinical practice and further research are presented.

PMID- 23875556
TI  - Social determinants of adolescent depression: an examination of racial
      differences.
AB  - Conventional behavior theories that assert adolescent risk behaviors are
      determined by peer and parental relationships are being challenged as research
      begins to consider broader socioenvironmental factors. This study, using data
      from the Longitudinal Study for Adolescent Health (Add Health), Wave II, Public
      Use Data, and the Social Determinants of Adolescent Risk Behaviors (SDOARB)
      framework, examines relationships among socioeconomic status (SES), academic
      performance, perceived peer prejudice, and perceived teacher discrimination as
      predictors of depressive symptoms among high school adolescents. Overall, the
      study found that GPA was a significant predictor of depressive symptoms across
      all three racial groups (Black, White, and Other Minority). Teacher
      discrimination predicted depressive symptoms among White and Other minority
      adolescents, but not Black adolescents. These findings suggest the need for
      interventions within schools for both students and teachers around racial
      differences in perceptions of prejudice and discrimination. Failure to address
      overt and covert subtleties of discrimination and prejudice within schools and
      policies which affect these interpersonal dynamics may have a significant impact
      on the overall mental wellbeing of adolescents. 

PMID- 23875557
TI  - Police experiences of committing people with mental illness to a hospital.
AB  - To a large extent today, caring for people with mental illness takes place
      outside of institutional care. Sometimes, assistance from a special police group
      may be required to commit the patient to a hospital for continued psychiatric
      treatment. The aim of this study was to describe a group of police officers and
      their experiences of committing individuals with mental illness to the hospital
      for treatment. Two specialised commitment groups within the police were
      interviewed. A qualitative content analysis was used to identify topics of
      greater significance in the data. The interviews show that the informants desire
      greater cooperation with psychiatric care personnel and want to know more about
      mental illness and how to approach those with mental illness. 

PMID- 23875559
TI  - Western cultural notions of time and stress.

PMID- 23875560
TI  - Engaging with voices: rethinking the clinical treatment of psychosis.
AB  - Although the hearing voices movement (HVM) has yet to take root in the US to the
      extent it has in the UK (and parts of Australia and Europe), recent publications
      and events, including a keynote presentation by UK hearing voices trainer Ron
      Coleman at the 2012 Annual NAMI convention and a TED 2013 talk in Los Angeles by
      British voice hearer and psychologist Eleanor Longden, suggest that the tide is
      starting to turn (Arenella, 2012; Grantham, 2012; Thomas, 2012). At its core, the
      HVM emphasizes a few basic, but important, points: that antipsychotic
      pharmacotherapy and various forms of psychotherapy that aim to suppress psychotic
      experiences are often--for too many people--ineffective or insufficient; that
      voices and other extreme experiences and beliefs carry important messages that
      need to be explored rather than silenced, and that voices themselves are often
      less of the problem than the difficulties individuals have in coping and
      negotiating with them (Corstens, Escher, & Romme, 2008; Longden, Corstens,
      Escher, & Romme, 2012; Place, Foxcroft, & Shaw, 2011).

PMID- 23875561
TI  - Screening of antidiabetic and antihyperlipidemic potential of oil from Piper
      longum and piperine with their possible mechanism.
AB  - BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by
      hyperglycaemia and other symptoms like polyuria (frequent urination), polydipsia
      (increased thirst) and polyphagia (increased hunger) which ultimately causes
      various other complications like retinopathy, neuropathy, nephropathy and
      microangiopathy. OBJECTIVES: The antidiabetic and antihyperlipidemic potential of
      oil from Piper longum (PLO) and piperine was investigated with their possible
      mechanism using alpha-glucosidase, aldose reductase (AR), and pancreatic lipase
      inhibitory activity. METHODS: The biochemical parameters, viz. glucose level,
      insulin level, liver glycogen content, glycosylated hemoglobin, total plasma
      cholesterol, triglyceride, and antioxidant parameters, were estimated for all
      treated groups in acute and chronic antihyperglycemic animal models. RESULTS: PLO
      (100 and 200 mg/kg), piperine (25 and 50 mg/kg), and glibenclamide (0.6 mg/kg) in
      respective groups of diabetic animals administered for 28 days reduced the blood
      glucose level in streptozotocin-induced diabetic rats. There was significant
      increase in body weight, liver glycogen content, plasma insulin, and high-density
      lipoprotein and decrease in glycosylated hemoglobin, triglyceride, and total
      plasma cholesterol in PLO-administered groups as compared to control group. The
      IC50 value of PLO for alpha-glucosidase, AR, and pancreatic lipase was found to
      be 150 +/- 2.5, 120 +/- 1.2, and 175 +/- 1.2 MUg/ml, respectively, which was
      found comparable with the standard drugs acarbose (90 +/- 2.3 MUg/ml), quercetin
      (80 +/- 2.3 MUg/ml), and orlistat (25 +/- 0.5 MUg/ml), respectively. CONCLUSION:
      The investigation done reveals that PLO has significant antidiabetic and
      antihyperlipidemic activity.

PMID- 23875562
TI  - TMEM106B and frontotemporal lobar degeneration: can over-expression tell us how
      reductions are beneficial?

PMID- 23875563
TI  - Exploring the boundary of a specialist service for adults with intellectual
      disabilities using a Delphi study: a quantification of stakeholder participation.
AB  - BACKGROUND: There are arguments that a specialist service for adults with
      intellectual disabilities is needed to address the health inequalities that this
      group experiences. The boundary of such a specialist service however is unclear,
      and definition is difficult, given the varying experiences of the multiple
      stakeholder groups. OBJECTIVES: The study reported here quantitatively
      investigates divergence in stakeholders' views of what constitutes a good
      specialist service for people with intellectual disabilities. It is the first
      step of a larger project that aims to investigate the purpose, function and
      design of such a specialist service. The results are intended to support policy
      and service development. STUDY DESIGN: A Delphi study was carried out to elicit
      the requirements of this new specialist service from stakeholder groups. It
      consisted of three panels (carers, frontline health professionals, researchers
      and policymakers) and had three rounds. The quantification of stakeholder
      participation covers the number of unique ideas per panel, the value of these
      ideas as determined by the other panels and the level of agreement within and
      between panels. FINDINGS: There is some overlap of ideas about of what should
      constitute this specialist service, but both carers and frontline health
      professionals contributed unique ideas. Many of these were valued by the
      researchers and policymakers. Interestingly, carers generated more ideas
      regarding how to deliver services than what services to deliver. Regarding
      whether ideas are considered appropriate, the variation both within and between
      groups is small. On the other hand, the feasibility of solutions is much more
      contested, with large variations among carers. CONCLUSIONS: This study provides a
      quantified representation of the diversity of ideas among stakeholder groups
      regarding where the boundary of a specialist service for adults with learning
      disabilities should sit. The results can be used as a starting point for the
      design process. The study also offers one way to measure the impact of
      participation for those interested in participation as a mechanism for service
      improvement.

PMID- 23875564
TI  - Mnemonic networks in the hippocampal formation: from spatial maps to temporal and
      conceptual codes.
AB  - The hippocampal formation has been associated with a wide variety of functions
      including spatial navigation and planning, memory encoding and retrieval,
      relational processing, novelty detection, and imagination. These functions are
      dissimilar in terms of their behavioral consequences and modality of
      representation. Consequently, theoretical standpoints have focused on explaining
      the role of the hippocampal formation in terms of either its spatial or
      nonspatial functions. Contrary to this dichotomy, we propose that it is essential
      to look beyond these traditional boundaries between mnemonic and spatial
      functions and focus instead on the processes that these functions have in common.
      In this framework, we use electrophysiology data from the spatial domain to
      predict effects on the systems level, both in spatial and nonspatial domains. We
      initially outline the results of studies that have used findings from spatial
      navigation in rodents to predict the patterns of brain activity observable in
      people who are exploring virtual environments. We discuss how certain properties
      of space-defining neurons enable space to be represented as a mental map of
      interconnected locations, which are expressed at multiple spatial scales in
      separate modules in the hippocampal formation. We then suggest that memories are
      also organized in networks, characterized by mnemonic and temporal hierarchies.
      We finish by discussing how virtual-reality techniques can be used to create
      novel lifelike episodes allowing us to look at episodic memory processes while
      multivariate analysis tools can be used to explore the organizational structure
      of mnemonic networks.

PMID- 23875565
TI  - Long-term memory representations influence perception before edges are assigned
      to objects.
AB  - One way to prioritize limited mental resources for perception is to take into
      account the familiarity of an object to the perceiver. But does an objects'
      familiarity influence perception only after an object's shape has been
      determined, or does it influence the decision of which edges are considered part
      of that object? Here we compare the influence of target familiarity on whole
      object masking (object-substitution masking) with its influence on edge-based
      masking. Two new aspects of edge-based masking are reported. First, we
      demonstrate that mask and target edges do not only compete (object trimming) but
      that mask and target edges can also cooperate (object binding), confirming that
      these masking effects are indeed occurring during the process of object formation
      and not after object shape has been determined. Second, we find that object
      trimming and binding are each less likely if the target is linked with a
      representation already present in long-term memory. Since trimming and binding
      effects arise very early in visual perception, these data indicate that existing
      long term memory representations influence the earliest stages of object
      assembly, before the system has even decided which edges to include in the
      object.

PMID- 23875566
TI  - Workplace bullying: the effectiveness of a workplace program.
AB  - Workplace bullying can not only cost thousands of dollars to replace an affected
      nurse, but also have detrimental economic effects on health care organizations.
      Occupational health nurses can provide leadership in preventing or eliminating
      workplace bullying. This pilot study determined that attendance at a cognitive
      rehearsal program decreased workplace bullying. The study used an Internet-based
      survey administered 6 months after nurses completed the 2-hour cognitive
      rehearsal program. Half of the nurses reported witnessing bullying behaviors
      since attending the program; 70% of the nurses reported changing their own
      behaviors following the course; and 40% of the nurses reported a decrease in
      bullying behaviors during the past 6 months. Although 70% of the nurses believed
      they could intervene in bullying situations, only 16% reported they responded to
      bullying at the time of occurrence. This study illuminates the need to continue
      searching for other effective methods to prevent and manage workplace bullying.

PMID- 23875567
TI  - Implementing a sharps injury reduction program at a charity hospital in India.
AB  - Health care workers in India are at high risk of developing bloodborne infections
      from needlestick injuries. Indian hospitals often do not have the resources to
      invest in safety devices and protective equipment to decrease this risk. In
      collaboration with hospital staff, the primary author implemented a sharps injury
      prevention and biomedical waste program at an urban 60-bed charity hospital in
      northern India. The program aligned with hospital organizational objectives and
      was designed to be low-cost and sustainable. Occupational health nurses working
      in international settings or with international workers should be aware of
      employee and employer knowledge and commitment to occupational health and safety.

PMID- 23875568
TI  - Creating meaningful partnerships between communities and environmental health
      researchers: the role of a direct action community organizing agency.
AB  - Community engagement is a necessary, although challenging, element of
      environmental health research in communities. To facilitate the engagement
      process, direct action community organizing agencies can be useful in bringing
      together communities and researchers. This article describes the preliminary
      activities that one direct action community organizing agency used in partnership
      with researchers to improve community engagement in the first 6 months of an
      environmental health study conducted in a major U.S. city. Activities included
      developing communication strategies, creating opportunities for researcher
      community interaction, and sustaining project momentum. To conduct environmental
      research that is both scientifically rigorous and relevant to communities,
      collaborating partners had to develop professional skills and strategies outside
      of their areas of expertise.

PMID- 23875569
TI  - High and low roads to odor valence? A choice response-time study.
AB  - Valence and edibility are two important features of olfactory perception, but it
      remains unclear how they are read out from an olfactory input. For a given odor
      object (e.g., the smell of rose or garlic), does perceptual identification of
      that object necessarily precede retrieval of information about its valence and
      edibility, or alternatively, are these processes independent? In the present
      study, we studied rapid, binary perceptual decisions regarding odor detection,
      object identity, valence, and edibility for a set of common odors. We found that
      decisions regarding odor-object identity were faster than decisions regarding
      odor valence or edibility, but slower than detection. Mediation analysis revealed
      that odor valence and edibility decision response times were predicted by a model
      in which odor-object identity served as a mediator along the perceptual pathway
      from detection to both valence and edibility. According to this model, odor
      valence is determined through both a "low road" that bypasses odor objects and a
      "high road" that utilizes odor-object information. Edibility evaluations are
      constrained to processing via the high road. The results outline a novel causal
      framework that explains how major perceptual features might be rapidly extracted
      from odors through engagement of odor objects early in the processing stream.

PMID- 23875571
TI  - The costs of cooperation: action-specific perception in the context of joint
      action.
AB  - A growing empirical literature has demonstrated that perceptions of the physical
      environment are influenced by the perceiver's behavioral ability. However, prior
      research has focused only on the perceptual consequences of individual behavior,
      despite the fact that individuals regularly take part in cooperative social
      interaction. To test whether similar effects occur as a result of engaging in
      joint action, we asked participants to estimate anticipated walking distance to a
      target location when expecting to carry a heavy object either alone or jointly
      with a confederate. Surprisingly, even though carrying with another person
      requires less physical effort, on certain carrying tasks participants estimated
      distances to be farther when expecting help. However, this effect was reversed
      when participants were asked to focus on the difficulty of the task or told about
      the alternative experimental condition, thereby making salient for joint carriers
      the potential, presumably negative, counterfactual of having to work alone.
      Findings are explained in terms of an ecological approach, which conceptualizes
      perception as the detection of information specifying affordances. These results
      highlight the limitations of purely effortful accounts of such phenomena and
      demonstrate the unique way in which social factors relevant to coordination can
      alter how people relate to their physical environments.

PMID- 23875570
TI  - The attentional effects of single cues and color singletons on visual
      sensitivity.
AB  - Sudden changes in the visual periphery can automatically draw attention to their
      locations. For example, the brief flash of a single object (a "cue") rapidly
      enhances contrast sensitivity for subsequent stimuli in its vicinity. Feature
      singletons (e.g., a red circle among green circles) can also capture attention in
      a variety of tasks. Here, we evaluate whether a peripheral cue that enhances
      contrast sensitivity when it appears alone has a similar effect when it appears
      as a color singleton, with the same stimuli and task. In four experiments we
      asked observers to report the orientation of a target Gabor stimulus, which was
      preceded by an uninformative cue array consisting either of a single disk or of
      16 disks containing a color or luminance singleton. Accuracy was higher and
      contrast thresholds lower when the single cue appeared at or near the target's
      location, compared with farther away. The color singleton also modulated
      performance but to a lesser degree and only when it appeared exactly at the
      target's location. Thus, this is the first study to demonstrate that cueing by
      color singletons, like single cues, can enhance sensory signals at an early stage
      of processing.

PMID- 23875573
TI  - Pitch memory and exposure effects.
AB  - Recent studies indicate that the ability to represent absolute pitch values in
      long-term memory, long believed to be the possession of a small minority of
      trained musicians endowed with "absolute pitch," is in fact shared to some extent
      by a considerable proportion of the population. The current study examined
      whether this newly discovered ability affects aspects of music and auditory
      cognition, particularly pitch learning and evaluation. Our starting points are
      two well-established premises: (1) frequency of occurrence has an influence on
      the way we process stimuli; (2) in Western music, some pitches and musical keys
      are much more frequent than others. Based on these premises, we hypothesize that
      if absolute pitch values are indeed represented in long-term memory, pitch
      frequency of occurrence in music would significantly affect cognitive processes,
      in particular pitch learning and evaluation. Two experiments were designed to
      test this hypothesis in participants with no absolute pitch, most with little or
      no musical training. Experiment 1 demonstrated a faster response and a learning
      advantage for frequent pitches over infrequent pitches in an identification task.
      In Experiment 2, participants evaluated infrequent pitches as more pleasing than
      frequent pitches when presented in isolation. These results suggest that absolute
      pitch representation in memory may play a substantial, hitherto unacknowledged
      role in auditory (and specifically musical) cognition.

PMID- 23875572
TI  - Visual search for color and shape: when is the gaze guided by feature
      relationships, when by feature values?
AB  - One of the most widespread views in vision research is that top-down control over
      visual selection is achieved by tuning attention to a particular feature value
      (e.g., red/yellow). Contrary to this view, previous spatial cueing studies showed
      that attention can be tuned to relative features of a search target (e.g.,
      redder): An irrelevant distractor (cue) captured attention when it had the same
      relative color as the target (e.g., redder), and failed to capture when it had a
      different relative color, regardless of whether the distractor was similar or
      dissimilar to the target. The present study tested whether the same effects would
      be observed for eye movements when observers have to search for a color or shape
      target and when selection errors were very noticeable (resulting in an erroneous
      eye movement to the distractor). The results corroborated the previous findings,
      showing that capture by an irrelevant distractor does not depend on the
      distractor's similarity to the target but on whether it matches or mismatches the
      relative attributes of the search target. Extending on previous work, we also
      found that participants can be pretrained to select a color target in virtue of
      its exact feature value. Contrary to the prevalent feature-based view, the
      results suggest that visual selection is preferentially biased toward the
      relative attributes of a search target. Simultaneously, however, visual selection
      can be biased to specific color values when the task requires it, which rules out
      a purely relational account of attention and eye movements.

PMID- 23875574
TI  - Components of working memory and visual selective attention.
AB  - Load theory (Lavie, N., Hirst, A., De Fockert, J. W., & Viding, E. [2004]. Load
      theory of selective attention and cognitive control. Journal of Experimental
      Psychology: General, 133, 339-354.) proposes that control of attention depends on
      the amount and type of load that is imposed by current processing. Specifically,
      perceptual load should lead to efficient distractor rejection, whereas working
      memory load (dual-task coordination) should hinder distractor rejection. Studies
      support load theory's prediction that working memory load will lead to larger
      distractor effects; however, these studies used secondary tasks that required
      only verbal working memory and the central executive. The present study examined
      which other working memory components (visual, spatial, and phonological)
      influence visual selective attention. Subjects completed an attentional capture
      task alone (single-task) or while engaged in a working memory task (dual-task).
      Results showed that along with the central executive, visual and spatial working
      memory influenced selective attention, but phonological working memory did not.
      Specifically, attentional capture was larger when visual or spatial working
      memory was loaded, but phonological working memory load did not affect
      attentional capture. The results are consistent with load theory and suggest
      specific components of working memory influence visual selective attention.

PMID- 23875575
TI  - Pushing typists back on the learning curve: revealing chunking in skilled
      typewriting.
AB  - Theories of skilled performance propose that highly trained skills involve
      hierarchically structured control processes. The present study examined and
      demonstrated hierarchical control at several levels of processing in skilled
      typewriting. In the first two experiments, we scrambled the order of letters in
      words to prevent skilled typists from chunking letters, and compared typing words
      and scrambled words. Experiment 1 manipulated stimulus quality to reveal chunking
      in perception, and Experiment 2 manipulated concurrent memory load to reveal
      chunking in short-term memory (STM). Both experiments manipulated the number of
      letters in words and nonwords to reveal chunking in motor planning. In the next
      two experiments, we degraded typing skill by altering the usual haptic feedback
      by using a laser-projection keyboard, so that typists had to monitor keystrokes.
      Neither the number of motor chunks (Experiment 3) nor the number of STM items
      (Experiment 4) was influenced by the manipulation. The results indicate that the
      utilization of hierarchical control depends on whether the input allows chunking
      but not on whether the output is generated automatically. We consider the role of
      automaticity in hierarchical control of skilled performance.

PMID- 23875576
TI  - Fractal dynamics in dexterous tool use: the case of hammering behavior of bead
      craftsmen.
AB  - Dexterous behavior exhibits exquisite context sensitivity, implying the efficacy
      of exploration to detect the task-relevant information. Inspired by the recent
      finding that fractal scaling of exploratory movements predicts how well the
      movements sample available perceptual information, we investigate the possibility
      that dexterity of craftsmen would be characterized by fractal (long-range)
      temporal correlation properties of fluctuations in their movement wielding a
      tool. A reanalysis of hammering behavior involved in stone beads production in
      India (Nonaka & Bril, 2012) revealed the presence of long-range, power-law
      correlations, as part of multiplicative cascades operating over a wide range of
      time scales. In the unfamiliar condition using unusual material, the wielding
      behavior of highly skilled experts displayed a significant increase of long-range
      temporal correlations, whereas that of less experts exhibited a significant loss
      of long-range correlations and reduced heterogeneity of scaling properties over
      time, which robustly discriminated the groups with different skill levels.
      Alterations in long-range correlation properties of movement fluctuations are
      apparently associated with changes in the situation differently depending on the
      level of expertise.

PMID- 23875577
TI  - When are abrupt onsets found efficiently in complex visual search? Evidence from
      multielement asynchronous dynamic search.
AB  - Previous work has found that search principles derived from simple visual search
      tasks do not necessarily apply to more complex search tasks. Using a Multielement
      Asynchronous Dynamic (MAD) visual search task, in which high numbers of stimuli
      could either be moving, stationary, and/or changing in luminance, Kunar and
      Watson (M. A Kunar & D. G. Watson, 2011, Visual search in a Multi-element
      Asynchronous Dynamic (MAD) world, Journal of Experimental Psychology: Human
      Perception and Performance, Vol 37, pp. 1017-1031) found that, unlike previous
      work, participants missed a higher number of targets with search for moving items
      worse than for static items and that there was no benefit for finding targets
      that showed a luminance onset. In the present research, we investigated why
      luminance onsets do not capture attention and whether luminance onsets can ever
      capture attention in MAD search. Experiment 1 investigated whether blinking
      stimuli, which abruptly offset for 100 ms before reonsetting--conditions known to
      produce attentional capture in simpler visual search tasks--captured attention in
      MAD search, and Experiments 2-5 investigated whether giving participants advance
      knowledge and preexposure to the blinking cues produced efficient search for
      blinking targets. Experiments 6-9 investigated whether unique luminance onsets,
      unique motion, or unique stationary items captured attention. The results found
      that luminance onsets captured attention in MAD search only when they were
      unique, consistent with a top-down unique feature hypothesis.

PMID- 23875578
TI  - Self-assembled graphene-dextran nanohybrid for killing drug-resistant cancer
      cells.
AB  - A nanohybrid based on nanoscale graphene oxide (NGO) and dextran has been
      designed and employed for effectively killing drug-resistant MCF-7/ADR cells.
      This graphene-based nanohybrid was readily prepared through pi-pi interaction of
      NGO and hematin-terminated dextran (HDex), being denoted as NGO-HDex. It revealed
      an improved stability in physiological conditions as compared to native NGO.
      Besides, NGO-HDex could efficiently load doxorubicin (DOX), an anticancer drug,
      with drug loading capacity of 3.4 mg/mg NGO and liberate the drug with a pH
      dependent profile. Cell viability assay indicated that the NGO-HDex displayed
      lower cytotoxicity against MCF-7/ADR cells as compared to native NGO. DOX-loaded
      NGO-HDex, however, revealed more efficient killing effect in the cells than free
      DOX because the nanohybrid caused a higher amount of DOX accumulated in the
      cells. The results of this study highlight that the NGO-HDex has high potential
      for killing drug-resistant cancer cells. 

PMID- 23875579
TI  - Development of a competitive indirect enzyme-linked immunosorbent assay based on
      monoclonal antibodies for the detection of 2-dodecylcyclobutanone in irradiated
      beef.
AB  - A highly sensitive and specific competitive indirect enzyme-linked immunosorbent
      assay (ciELISA) based on monoclonal antibodies was developed for the detection of
      2-dodecylcyclobutanone (2-DCB), a chemical marker for irradiated lipid-containing
      foods. 2-Oxocyclobutane undecanoic acid was used as an alternative to 2-DCB and
      conjugated to BSA and OVA via a conventional carbodiimide condensation reaction
      to prepare the immunogen and the coating antigen for 2-DCB. The monoclonal
      antibody against 2-DCB was obtained using the hybridoma technique, with a high
      specificity and low cross-reactivity for 2-tetradecylcyclobutanone (2-TCB; <8%)
      and other structurally related compounds (<0.1%). The ciELISA method was
      applicable at optimal experimental conditions of 0.001-100 MUg/mL 2-DCB in a
      buffer solution, with an IC50 value of 0.25 MUg/mL and a limit of detection
      (defined as the IC20) of approximately 0.004 MUg/mL. The recovery efficiency of 2
      DCB from ground beef patties ranged from 84.4 to 109.8%. The intra-assay and
      interassay coefficients of variation were <10.0 and <12.0%, respectively. The
      proposed method was validated by gas chromatography-mass spectrometry with high
      correlation. The same method was used to detect 2-DCB in ground beef patties
      irradiated at 0.5, 1.0, 3.0, 5.0, and 7.0 kGy; the 2-DCB concentration linearly
      increased with the radiation dose.

PMID- 23875580
TI  - Synthesis, characterization, and relative stabilities of self-assembled
      monolayers on gold generated from bidentate n-alkyl xanthic acids.
AB  - A series of self-assembled monolayers (SAMs) on gold were generated by the
      adsorption of n-alkyl xanthic acids (NAXAs) having the general formula
      CH3(CH2)nOCS2H (n = 12-15). The structural features of these SAMs were
      characterized by optical ellipsometry, contact angle goniometry, polarization
      modulation infrared reflection absorption spectroscopy (PM-IRRAS), and X-ray
      photoelectron spectroscopy (XPS). This series of xanthate SAMs were compared to
      SAMs generated from the corresponding n-alkanethiols and aliphatic
      dithiocarboxylic acids (ADTCAs). The collected data indicate that the NAXAs
      generate densely packed and well-ordered monolayers. The contact angles of
      hexadecane on the xanthate monolayers exhibited a large "odd-even" effect similar
      to that produced by the ADTCA SAMs. The relative stability of these bidentate
      xanthate SAMs was evaluated by monitoring the changes in ellipsometric
      thicknesses and wettability as a function of time under various conditions. The
      results demonstrate that SAMs formed from NAXAs are much less stable than
      analogous n-alkanethiolate and ADTCA SAMs. 

PMID- 23875582
TI  - Structural, spectroscopic, and computational characterization of the azide adduct
      of Fe(III)(2,6-diacetylpyridinebis(semioxamazide)), a functional analogue of iron
      superoxide dismutase.
AB  - We have prepared and thoroughly characterized, using X-ray crystallographic,
      spectroscopic, and computational methods, the diazide adduct of
      [Fe(III)(dapsox)(H2O)2](+) [dapsox = 2,6-diacetylpyridinebis(semioxamazide)],
      (1), a low-molecular weight, functional analogue of iron superoxide dismutase
      (FeSOD). The X-ray crystal structure of the dimeric form of 1,
      (Na[Fe(III)(dapsox)(N3)2].DMF)2 (2) shows two axially coordinated, symmetry
      inequivalent azides with differing Fe-N3 bond lengths and Fe-N-N2 bond angles.
      This inequivalence of the azide ligands likely reflects the presence of an
      interdimer hydrogen bonding interaction between a dapsox NH group and the
      coordinated nitrogen of one of the two azide ligands. Resonance Raman (rR) data
      obtained for frozen aqueous solution and solid-state samples of 2 indicate that
      the azides remain inequivalent in solution, suggesting that one of the azide
      ligands of 1 engages in an intermolecular hydrogen bonding interaction with a
      water molecule. Density functional theory (DFT) and time-dependent DFT
      calculations have been used to study two different computational models of 1, one
      using coordinates taken from the X-ray crystal structure of 2, and the other
      generated via DFT geometry optimization. An evaluation of these models on the
      basis of electronic absorption, magnetic circular dichroism, and rR data
      indicates that the crystal structure based model yields a more accurate
      electronic structure description of 1, providing further support for the proposed
      intermolecular hydrogen bonding of 1 in the solid state and in solution. An
      analysis of the experimentally validated DFT results for this model reveals that
      the azides have both sigma- and pi-bonding interactions with the Fe(III) center
      and that more negative charge is located on the Fe-bound, rather than on the
      terminal, nitrogen atom of each azide. These observations are reminiscent of the
      results previously reported for the azide adduct of FeSOD and provide clues
      regarding the origin of the high catalytic activity of Fe-dapsox for superoxide
      disproportionation. 

PMID- 23875581
TI  - Real-time electrochemical monitoring of adenosine triphosphate in the picomolar
      to micromolar range using graphene-modified electrodes.
AB  - We report on a competitive electrochemical detection system that is free of wash
      steps and enables the real-time monitoring of adenosine triphosphate (ATP) in a
      quantitative manner over a five-log concentration range. The system utilizes a
      recognition surface based on ATP aptamer (ATPA) capture probes prebound to
      electroactive flavin adenine dinucleotide (FAD) molecules, and a signaling
      surface utilizing graphene (Gr) and gold nanoparticle (AuNP) modified carbon
      paste electrode (Gr-AuNP-CPE) that is optimized to enhance electron-transfer
      kinetics and signal sensitivity. Binding of ATP to ATPA at the recognition
      surface causes the release of an equivalent concentration of FAD that can be
      quantitatively monitored in real time at the signaling surface, thereby enabling
      a wide linear working range (1.14 * 10(-10) to 3.0 * 10(-5) M), a low detection
      limit (2.01 * 10(-11) M using graphene and AuNP modified glassy carbon), and fast
      target binding kinetics (steady-state signal within 12 min at detection limit).
      Unlike assays based on capture probe-immobilized electrodes, this double-surface
      competitive assay offers the ability to speed up target binding kinetics by
      increasing the capture probe concentration, with no limitations due to
      intermolecular Coulombic interactions and nonspecific binding. We utilize the
      real-time monitoring capability to compute kinetic parameters for target binding
      and to make quantitative distinctions on degree of base-pair mismatch through
      monitoring target binding kinetics over a wide concentration range. On the basis
      of the simplicity of the assay chemistry and the quantitative detection of ATP
      within fruit and serum media, as demonstrated by comparison of ATP levels against
      those determined using a standard high-performance liquid chromatography (HPLC)
      UV absorbance method, we envision a versatile detection platform for applications
      requiring real-time monitoring over a wide target concentration range. 

PMID- 23875583
TI  - Oxidant-dependent chemoselectivity in the gold-catalyzed oxidative cyclizations
      of 3,4,6,6-tetrasubstituted 3,5-dien-1-ynes.
AB  - A distinct chemoselectivity in the gold-catalyzed oxidative cyclization of 3,5
      dien-1-ynes was observed when 3,5-dichloropyridine N-oxide replaced 8
      methylquinoline N-oxide as the oxidant; the resulting cyclopentadienyl aldehydes
      were obtained in good yields. The altered chemoselectivity is attributed to a
      prior enyne cyclization in the presence of 3,5-dichloropyridine N-oxides. The use
      of N-iminopyridium ylide enables a similar iminocyclization reaction to give
      cyclopentadienyl imines efficiently. Our experimental data support a prior gold
      catalyzed cyclization of 3,5-dien-1-ynes to form gold carbene, followed by the
      oxidation with N-oxide. 

PMID- 23875584
TI  - [Validity and reliability of Turkish version of St. George's respiratory
      questionnaire].
AB  - INTRODUCTION: The importance of the evaluation of health status in chronic
      obstructive pulmonary disease (COPD) is recently highlighted in many studies. In
      this study, we aimed to test the validity and reliability of the Turkish version
      of St. George Respiratory Questionnaire (SGRQ). MATERIALS AND METHODS: The study
      was conducted in seven centers in Turkey. Three hundred and twenty one COPD
      patients (40-75 years) were included to the study. Turkish versions of
      breathlessness, Cough, and Sputum Scale (BCSS), mMRC (Modified Medical Research
      Council) dyspnea scale, SGRQ, COPD assessment test (CAT) and Short Form Health
      Survey (SF-36) were carried out to the patients. The statistical analysis of SGRQ
      was performed by using the coefficient of internal consistency, discriminative
      analysis for different stages and the correlation with the other scales. RESULTS:
      The mean age was 62.4 +/- 8.9 years and the mean FEV1 was 51.9 +/- 19.2% pred.
      The coefficient of internal consistency (Cronbach alpha) was 0.8815. The
      correlation between the total score measured initially and that obtained two
      weeks later was found to be highly significant (r= 0.90, p< 0.0001). According
      the results of validation of both total score and the components of SGRQ, the
      correlation between the total score of SGRQ and CAT was 0.782 (p< 0.0001), SGRQ
      and SF-36 was between -0.481 ile -0.819 (p< 0.0001). The total and component
      scores were able to discriminate different disease stages and a significant
      correlation was found to be with pulmonary function tests. CONCLUSION: SGRQ
      Turkish version is a reliable and valid assessment tool for COPD patients in
      clinical practice.

PMID- 23875585
TI  - [The investigation of angiotensin converting enzyme I/D and plasminogen activator
      inhibitor-1 4G/5G polymorphisms in venous thromboembolism patients].
AB  - INTRODUCTION: Deep venous thrombosis and pulmonary embolism, known as venous
      thromboembolism and seen as a fairly common multifactorial diseases. Differ
      between populations due to genetic factors, several polymorphisms associated with
      venous thromboembolism was conducted. As a result of these studies the
      relationship between disease development and polymorphism is not clear yet. In
      this study we aimed to investigate the role of angiotensin converting enzyme
      insersion/deletion (ACE I/D) and plasminogen activator inhibitor-1 4G/5G (PAI-1
      4G/5G) polymorphism in the development of disease. MATERIALS AND METHODS: In our
      study, DNA isolated from 80 venous thromboembolism patients and 79 control groups
      was used. While the classical polymerase chain reaction method used to
      investigate the ACE I/D polymorphism, the polymerase chain reaction based on
      allele-specific amplification was used for the detection of PAI-1 4G/5G
      polymorphism. RESULTS: As a result, there were no significant statistical
      differences for ACE I/D and PAI-1 4G/5G polymorphism among patient and control
      groups (p> 0.05). CONCLUSION: These findings revealed that there is no
      relationship between these polymorphisms and the development of venous
      thromboembolism, but large-scale studies are need to be done.

PMID- 23875586
TI  - Delays in diagnosis and treatment of venous thromboembolism in a developing
      country setting.
AB  - INTRODUCTION: Rapid diagnosis and treatment of deep vein thrombosis and pulmonary
      thromboembolism reduce mortality and morbidity. The aim of this study is to
      investigate delays in treatment of deep vein thrombosis and pulmonary
      thromboembolism and related factor in a developing country. MATERIALS AND
      METHODS: We prospectively investigated 353 patients with diagnosis deep vein
      thrombosis and/or pulmonary thromboembolism in Urmia, Iran. We recorded dates of
      symptom onset, initial visit by a clinician, initiation of treatment, and
      confirmation of diagnosis. We also analyzed relation with some factors. RESULTS:
      The mean interval from symptoms onset to initiation of treatment was 4.70 days,
      89% of this interval was between onset of symptoms to first medical evaluation
      (mean= 4.19 days). Mean time from onset of symptoms to confirmation of diagnosis
      was 6.29 days. Of 353 patients with venous thromboembolism 185 (52.4%) visited by
      a physician within two days of onset of symptoms and 168 (47.6%) patients after
      two days. Factors that was associated with earlier seeking with p value < 0.05
      were pulmonary thromboembolism patients earlier than deep vein thrombosis, higher
      education, recent surgery, presence of cast, entire leg swelling. There was no
      association between age, gender, number of symptoms, and presence familial
      history of venous thromboembolism (all p value > 0.05). The delays time from
      first visit to final diagnosis was significantly shorter in patients with high
      probability score. CONCLUSION: Most patients with venous thromboembolism received
      anti-coagulation and diagnosis with delay. The main cause of delay is related to
      patient's delays. There is a need to improve people awareness about venous
      thromboembolism and to develop strategies to reduce delays.

PMID- 23875587
TI  - [Diagnostic value of pleural fluid and serum procalcitonin levels in the
      diagnosis of parapneumonic pleural effusion].
AB  - INTRODUCTION: To determine the diagnostic value of pleural fluid procalcitonin
      (PF-PCT) and serum PCT (S-PCT) levels in the diagnosis of parapneumonic pleural
      effusion (PPPE). MATERIALS AND METHODS: Sixty five inpatients with exudative
      pleural fluid were consecutively included in this prospective study. Biochemical
      (total protein, albumin, LDH, glucose, pH, PCT) studies were performed in
      concurrently obtained pleural fluid and venous blood samples, cytologic and
      microbiologic (acid-fast bacillus smear/culture, nonspecific bacterial Gram
      stain/culture, fungal culture) studies were performed in pleural fluid. The
      patients were grouped as PPPE (n= 33) and non-PPPE (n= 32) after the diagnoses
      were definitely established. RESULTS: A total of 65 patients (M/F: 38/27; age:
      57.53 +/- 18.46 years) with exudative pleural fluids were assessed. In the 33
      with PPPEs, 6 simple PPPEs, 5 complicated PPPEs and 22 empyemas were determined
      whereas in the 32 non-PPPEs, 9 tuberculous, 10 malignant, 6 paramalignant, 5 non
      specific effusions and 2 chylothoraces were determined. Compared with the non
      PPPE group, more fever, pneumonic infiltrations and fluid loculation, higher
      sedimentation, leukocyte, fluid LDH besides lower fluid glucose, pH, albumin and
      protein together with lower serum LDH were determined in the PPPE group (p<
      0.05). Higher PS-PCT (1.03 +/- 1.27 vs. 0.06 +/- 0.06 ng/mL) and S-PCT levels
      (0.90 +/- 1.44 vs. 0.05 +/- 0.02 ng/mL) were determined in the PPPE group (p=
      0.000). In the PPPE group, PS-PCT and S-PCT showed positive correlation with each
      other while PS-PCT did with sedimentation, leukocyte, CURB-65 and serum LDH, and
      S-PCT did with sedimentation, CURB-65 and duration of hospitalization. ROC curve,
      a specificity of 96.9% and a sensitivity of 57.5% were determined for an optimal
      PS-PCT cut-off level (0.285 ng/mL), and a specificity of %96.9 and a sensitivity
      of %66.6 for an optimal S-PCT cut-off level (0.105 ng/mL) that could
      differentiate PPPE. CONCLUSION: PS/S-PCT levels were found to be highly efficient
      in excluding PPPE but not sufficiently reliable in the diagnosis of it. However,
      these findings should be reassessed in a larger group of cases that have not been
      given any antibiotic/anti-inflammatory treatment.

PMID- 23875588
TI  - Study of pyrazinamidase structural changes in pyrazinamide resistant and
      susceptible isolates of Mycobacterium tuberculosis.
AB  - INTRODUCTION: Pyrazinamide is one of the first line four drugs for treatment of
      tuberculosis. It was proved that mutations in two nucleotides of 359 and 374 pnc
      genes are highly associated with resistance to pyrazinamide. MATERIALS AND
      METHODS: In this study, mutations in these two codones in 30 clinical isolates of
      Mycobacterium tuberculosis were detected by means of sequencing. Protein
      structures encoded by this gene with and without mutation were investigated in
      resistant and susceptible isolates to pyrazinamide, respectively. RESULTS:
      Mutation in the positions 359 and 374 altered some parameters like change in
      electronic charge, distance change of mutated amino acids to situation of active
      enzyme and metal connection situation. In these conditions, structure and
      function of pyrozinamidase enzyme were changed and antibiotic was ineffective and
      consequently caused resistance to pyrazinamide in M. tuberculosis. CONCLUSION:
      This work was revealed protein changes in resistance to pyrazinamide in clinical
      isolates of M. tuberculosis.

PMID- 23875589
TI  - Biomass smoke exposure as a serious health hazard for women.
AB  - INTRODUCTION: Lung diseases caused by biomass exposure cause a significant health
      hazard particularly amongst women. The present study was designed to investigate
      biomass exposure in women suffering from lung disease. MATERIALS AND METHODS: A
      total of 100 women [mean (SD) age: 55.13 (17.65) years] hospitalized for chronic
      obstructive pulmonary disease (COPD), asthma, bronchiectasis, tuberculosis or
      interstitial lung disease were included in this study conducted between September
      2008-March 2009 in three chest disease clinics at Sureyyapasa Chest Diseases and
      Chest Surgery Training and Research Hospital. Data collection on biomass exposure
      was based on application of hospital-based survey questionnaire including items
      on occupation, level of education, place of birth (location, region), exposure to
      biomass fuel fumes for heating and cooking purposes (animal dung, wood, charcoal,
      dried plant) and years of exposure with animal dung, wood, charcoal, dried plant.
      RESULTS: COPD in 22% patients, lung carcinoma in 12%, bronchitis in 8%,
      tuberculosis in 26%, and interstitial lung disease in 17% were the diagnosis for
      hospitalization. The most identified occupation was housewifery 86%. Active,
      former and non-smokers composed 6%, 22% and 72% of the population. Birth place
      was village in 67% patients while districts in 9%. According to regional
      distribution, the most common place of birth was Central Anatolia region in
      (29%). Exposure to biomass fuels was identified in all of patients including wood
      (92%), animal dung (30%), charcoal (23%), and dry plant (23%). Mean (SD) years of
      exposure was identified to be 52.6 (17.9) years for wood, 40.8 (17.9) years for
      animal dung, 48.1 (20.8) years for dry plant and 38.5 (21.4) years for charcoal.
      The most common type of biomass exposure was wood in village (97%), city (79%)
      and county (89%). CONCLUSION: Findings indicating impact of biomass exposure in
      women seem to emphasize the need for analytic epidemiologic studies assessment
      measuring biomass exposure levels-particularly for women and young children.

PMID- 23875590
TI  - [The clinical value of autofluorescence bronchoscopy for precancerous lesions in
      operable primary lung cancer patients].
AB  - INTRODUCTION: The aim of the present study is to show the role of
      autofluorescence bronchoscopy (AFB) compare with white light bronchoscopy (WLB)
      in detecting synchronous cancer and precancerous lesions in cases with operable
      primary lung cancer. MATERIALS AND METHODS: Fourty-nine patients were included in
      the study. WLB findings were grouped as group 1 normal, group 2 erithema or
      edema, group 3 nodular lesions or mucosal abnormality. AFB findings were grouped
      as group 1 normal, group 2 light brownish abnormal areas, group 3 brownish
      abnormal areas. Biopsies were obtained from group 2 and 3 patients. In 12 (24.5%)
      of the patients no areas were suspected and no biopsies were taken. RESULTS:
      Twenty-six (53%) of 49 patients did not show abnormal biopsy results in any of
      the specimens. One (2%) patient had metaplasia, 1 (2%) patient had dysplasia, 1
      (2%) patient had in situ carcinoma. The diagnostic accuracy rates for the
      detection of synchronous cancer and precancerous lesions using WLB and AFB were
      as follows respectively: sensitivity 77.8% vs. 100%; specificity 37.5% vs. 3%;
      positive predictive value 21.9% vs. 24.3%; negative predictive value 88.2% vs.
      100%. The relative sensitivity of AFB to WLB is 1.28. CONCLUSION: This study
      demonstrated that, AFB is an effective method in detecting synchronous cancer and
      precancerous lesions because of its low specificity it is more likely to be
      complementary to WLB.

PMID- 23875591
TI  - Comparison of health-related quality of life and exercise capacity according to
      stages in patients with non-small cell lung cancer.
AB  - INTRODUCTION: The aim of this study is to compare the exercise capacity and
      health-related quality of life parameters according to stages of patients with
      non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Fifty-two patients
      (who are able to ambulate independently) with stage I-II (group early-stage, n=
      17) and stage IIIA-IV NSCLC (group advanced-stage, n= 35) were included. Exercise
      capacity (six minute walking test), strength of the peripheral muscle (Back and
      Leg Dynamometer), performance status (Karnofsky performance status scale), health
      related quality of life- HRQOL (European Organization for Research and Treatment
      of Cancer Quality of life measure and Short Form-36 Health Survey), depression
      and anxiety (Hospital Anxiety and Depression Scale) were evaluated. RESULTS: No
      difference was found in age, body mass index, respiratory symptoms and the
      distribution of disease cell types between two groups (p> 0.05). In advanced
      stage group, pulmonary function test values, peripheral muscle strength, walking
      distance and health-related quality of life scores especially the categories of
      functional capacity and pain were established significantly lower compared to
      early-stage group (p <= 0.05). Depression and anxiety levels were confirmed to be
      similar between groups (p> 0.05). CONCLUSION: The exercise capacity of patients
      with advanced-stage NSCLC is lower due to reduced pulmonary functions and
      peripheral muscle strength compared to patients with early-stage NSCLC.
      Therefore, we can conclude that reduced exercise capacity negatively impacts
      functional categories of health related quality of life of patients with advanced
      stage NSCLC.

PMID- 23875592
TI  - Level of knowledge about anaphylaxis among health care providers.
AB  - INTRODUCTION: Level of knowledge about anaphylaxis was evaluated in health care
      providers by using a self-administered questionnaire. MATERIALS AND METHODS: A
      total of 1172 participants responded to the survey, and previously half of them
      had met a case with anaphylaxis with a highest rate in primary and a lowest rate
      in tertiary care (p= 0.005). RESULTS: 84.7% of participants answered the
      questions about the symptoms of anaphylaxis correctly. Although 62.6% of the
      group knew correctly anaphylaxis treatment steps, 44.7% of them agreed to
      administer epinephrine if they suspected of a subject with anaphylaxis. One third
      of the group indicated appropriate route of epinephrine administration. 85.2% of
      participants agreed to refer the patient to allergy clinic despite 33.7% of the
      group were unaware of where the nearest allergy clinic was. Only 20.3% of the
      respondents have heard about epinephrine auto-injector. CONCLUSION: Anaphylaxis
      was often diagnosed and managed inadequately, regardless of practice location,
      employment status and speciality in north-eastern Turkey.

PMID- 23875593
TI  - Oesophageal achalasia misdiagnosed as uncontrolled asthma.
AB  - Achalasia is characterized by incomplete lower oesophageal sphincter relaxation
      and aperistalsis of the oesophagus. It may present with dyspnea symptom. An 18
      years-old male patient applied to a clinic with the complaints of cough, dyspnea,
      wheezing and diagnosed as asthma. Although his asthma treatment was increased in
      time while he did not recover, he was reffered to our hospital with the diagnosis
      of uncontrolled asthma. On chest X-ray there was a mild upper mediastinal
      enlargement and chest computed tomography revealed an over-dilated oesophagus
      constricting the trachea. The patient was referred to chest surgery clinic with a
      suspected diagnosis of achalasia. Barium-oesophagogram and endoscopic evaluation
      of the oesophagus confirmed the diagnosis of achalasia. The patient underwent
      Heller myotomy and oesophagogastrostomy. He was recovered in one week after the
      surgery without any complaint of dyspnea. Spirometry tests and chest X-ray
      resulted normal in one year. With this case of achalasia who used asthma
      treatment unnecessarily,we wanted to emphasize the importance of differential
      diagnosis of difficult asthma. 

PMID- 23875594
TI  - Pleural empyema due to group A beta-hemolytic streptococci in a newborn: case
      report.
AB  - Pleural empyema is a rare and serious complication of pneumonia. Although it is
      frequently seen in children, there are only a few reports about pleural empyema
      in newborn infants. Here we report a case of early onset neonatal pneumonia
      complicated with pleural empyema. The causal microorganism was group A beta
      hemolytic streptococci (GAS or Streptococcus pyogenes) presumably originating
      from the mother, who had a puerperal infection. The mother had fever, pelvic
      pain, and abnormal vaginal discharge two days after delivery and subsequent
      increase in the antistreptolysin O titer, suggesting streptococcus infection. The
      patient was successfully treated by pleural drainage in addition to synergistic
      antimicrobial therapy. 

PMID- 23875595
TI  - [The yield of tigecycline in the treatment of community-acquired pneumonia].
AB  - Tigecycline is a novel antibiotic and it is the first glycylcycline of the
      tetracycline antibiotic class. It exhibits potent in vitro activity against
      causative pathogens that are most frequently isolated in patients with community
      acquired pneumonia. The objective of this study is to review the literature about
      the efficacy of tigecycline in community-acquired pneumonia. Two randomized
      clinical studies showed tigecycline was not inferior when compared with
      levofloxacin for the treatment of patients with bacterial community-acquired
      pneumonia requiring hospitalization. Tigecycline was generally well tolerated in
      patients with community-acquired pneumonia. Major adverse effects were primarily
      gastrointestinal in nature. Tigecycline offers an antibiotic option that can be
      used in hospitalized patients with mild to moderate community-acquired pneumonia.

PMID- 23875596
TI  - [Can anti-IgE be an alternative treatment for severe non-allergic asthma?].

PMID- 23875597
TI  - A case of primary spontaneous pneumothorax, pneumomediastinum and subcutaneous
      emphysema following cough.

PMID- 23875598
TI  - [Scientific publications concerning cardiopulmonary exercise testing: a glance
      from Turkey].

PMID- 23875599
TI  - Pulmonary arterial hypertension in antisynthetase syndrome without myositis.

PMID- 23875600
TI  - Analyzing structure-photophysical property relationships for isolated T8, T10,
      and T12 stilbenevinylsilsesquioxanes.
AB  - Silsesquioxanes (SQs) are of considerable interest for hybrid electronic and
      photonic materials. However, to date, their photophysical properties have not
      been studied extensively, thus their potential remains conjecture. Here we
      describe the first known efforts to map structure-photophysical properties as a
      function of cage symmetry and size by comparing identically functionalized
      systems. Our focus here is on the solution photophysical properties of the title
      stilbenevinyl-SQs, which were characterized using single photon absorption, two
      photon absorption, fluorescence emission, and fluorescence lifetime kinetics. We
      offer here the first detailed photophysical study of the larger pure T10 and T12
      silsesquioxanes and show photophysical properties that differ as a function of
      size, especially in their fluorescence behavior, indicating that cage size and/or
      symmetry can strongly affect photophysical properties. We also find that they
      offer excitation-dependent emission (evidence of rare "red-edge" effects). The
      T10 stilbenevinyl-SQ offers up to a 10-fold increase in two-photon absorption
      cross section per chromophore over a free chromophore, signifying increased
      electronic coupling. The SQ cage compounds show "rise times" of 700-1000 fs and
      low anisotropy (~0.1) in fluorescence lifetime kinetic studies. These results
      indicate excited state energy transfer, unobserved for the free chromophores and
      unexpected for systems with "inert" silica cores and for 3-D hybrid molecular
      species. These findings provide the first detailed photophysical study of
      chromophore-functionalized T10 and T12 silsesquioxanes and show that SQs may be
      considered a separate class of compounds/materials with anticipated novel
      properties of value in developing new components for electronic and photonic
      applications.

PMID- 23875601
TI  - Nitration of silyl allenes to form functionalized nitroalkenes.
AB  - An efficient nitration of silyl allenes with nitrogen dioxide radical, generated
      from NaNO2 and AcOH, to form alpha-nitro-alpha,beta-unsaturated silyl oximes has
      been developed. A similar nitration could be achieved by using Fe(NO3)3.9H2O and
      FeCl3.6H2O, but different from the regioselective oxime formation, two
      regioisomeric chloride-trapped products were isolated with varying ratios
      depending on the steric bulk of the silyl group. A novel ring-closure reaction of
      alpha-nitro-alpha,beta-unsaturated silyl oximes upon treating with TBAF to form
      isooxazolidinone derivatives was also developed. 

PMID- 23875602
TI  - Inability to detect human T cell lymphotropic virus type 2-specific antibodies in
      a patient coinfected with HIV-1, human T cell lymphotropic virus type 1, human T
      cell lymphotropic virus type 2, and hepatitis C virus.
AB  - HIV-1, human T cell lymphotropic virus type 1 and type 2 (HTLV-1 and HTLV-2) and
      hepatitis C virus (HCV) are common among intravenous drug users (IDUs) and can
      cause chronic infections in the host. Usually, the diagnosis of such viruses
      employs serological assays; however, some difficulties in confirming HTLV-2
      infection have been reported in high-risk populations in Brazil. We present data
      of an unusual case of coinfection with HIV-1, HTLV-1, HTLV-2, and HCV in a male
      IDU in which HTLV-2 was detected only by molecular assays. Comparative analysis
      of retroviruses from 2002 and 2012 showed identical HTLV-1 and HTLV-2 sequences
      (LTR, env, and tax), and a change in HIV-1 tropism from CXCR4 to CCR5. No
      mutation was detected in the hot points of the env region of the HTLV-2 isolate
      that justified the lack of rgp46-II-specific antibodies. These data emphasize the
      need for molecular assays to diagnose HTLV-2 in high-risk populations in Brazil.

PMID- 23875603
TI  - Comparative study of structure and permeability of porous oxide films on aluminum
      obtained by single- and two-step anodization.
AB  - A comparative study of the structure and transport properties of porous aluminum
      oxide films obtained by single- and two-step anodization was carried out. It is
      shown that the oxidation regime significantly affect the number of dead-ended
      channels, which results in more than twice the variation in membrane
      permeability. The effect is explained by multiple branching of channels on the
      initial stages of organization of the porous structure. Branching also occurs on
      later stages governing mass transport properties of porous anodic alumina films.
      A model describing transport properties of anodic aluminum oxide membranes based
      on pore branching on domain boundaries was suggested to fit experimental results
      of permeance of membranes obtained by both single- and two-step anodization. 

PMID- 23875604
TI  - Practice uncertainty: changing perceptions.
AB  - Practice uncertainty is inevitable in health care, and there are many contextual
      factors that can lead to either good or bad outcomes for patients and health care
      providers. Practice uncertainty is not a well-established concept in the
      literature, perhaps because of the predominant empirical paradigm and the high
      value placed on certainty within current health care culture. This study was
      conducted to explore practice uncertainty and bring this topic into the
      foreground as a first step toward practice evolution. A shift in the perception
      of practice uncertainty may change the way in which practitioners experience this
      phenomenon. This process must start with nursing educators recognizing and
      acknowledging this phenomenon when it occurs.

PMID- 23875605
TI  - Perspectives of unlicensed assistive personnel on career development.
AB  - BACKGROUND: An equivalency program, Method 3, is a viable but underused option
      for unlicensed assistive personnel (UAP) who pursue licensure. This study
      describes the perceptions of UAP on opportunities for career development.
      METHODS: Eighteen UAP participated in three focus groups. Thematic analysis was
      conducted with verbatim transcription. RESULTS: Three major themes represented
      the lively discussions that occurred: core driving forces, processes of career
      development, and anticipated and desirable outcomes. Various subthemes described
      these major themes. CONCLUSION: Method 3 provides a realistic approach to help
      UAP persevere with career development. Collaboration with management and peers,
      encouragement, and effective communication contributed to the success of
      participants, despite obstacles and challenges. Camaraderie and flexible
      scheduling were critical elements in participants' pursuit of first licensure.
      Taking small steps was described as an effective approach for UAP to persevere
      with career development. Support for informal career development is essential.
      Nursing leaders should consider an equivalency approach to accommodate individual
      preferences and learning needs for career development.

PMID- 23875606
TI  - Development of a whole-cell biocatalyst/biosensor by display of multiple
      heterologous proteins on the Escherichia coli cell surface for the detoxification
      and detection of organophosphates.
AB  - This paper reports the codisplay of organophosphorus hydrolase (OPH) and methyl
      parathion hydrolase (MPH)-green fluorescent protein (GFP) fusion on the cell
      surface of Escherichia coli using the truncated ice nucleation protein (INPNC)
      and Lpp-OmpA as the anchoring motifs. The surface localization of both OPH and
      MPH-GFP was demonstrated by cell fractionation, Western blot analysis, protease
      accessibility experiment, and immunofluorescence microscopy. Anchorage of the
      foreign proteins on the outer membrane neither inhibits cell growth nor affects
      cell viability. The recombinant strain can be used as a whole-cell biocatalyst
      and showed a broader substrate range than strains expressing either OPH or MPH. A
      mixture of six organophosphorus pesticides (OPs) (0.2 mM each) could be degraded
      completely within 5 h. The broader substrate specificity in combination with the
      rapid degradation rate makes the recombinant strain a promising candidate for
      detoxification of OPs. The fluorescence of surface-displayed GFP is very
      sensitive to environmental pH change. Because hydrolysis of OPs by OPH or MPH
      generates protons, the recombinant E. coli could be used as a whole-cell
      biosensor for the rapid detection of OPs by evaluating fluorescence changes as a
      function of OP concentrations. 

PMID- 23875607
TI  - Magnetophoresis-integrated hydrodynamic filtration system for size- and surface
      marker-based two-dimensional cell sorting.
AB  - A simple microfluidic system has been presented to perform continuous two
      parameter cell sorting based on size and surface markers. Immunomagnetic bead
      conjugated cells are initially sorted based on size by utilizing the hydrodynamic
      filtration (HDF) scheme, introduced into individual separation lanes, and
      simultaneously focused onto one sidewall by the hydrodynamic effect. Cells are
      then subjected to magnetophoretic separation in the lateral direction, and
      finally they are individually recovered through multiple outlet branches. We
      successfully demonstrated the continuous sorting of JM (human lymphocyte cell
      line) cells using anti-CD4 immunomagnetic beads and confirmed that accurate size-
      and surface marker-based sorting was achieved. In addition, the sorting of cell
      mixtures was performed at purification ratios higher than 90%. The proposed
      system enables two-dimensional cell sorting without necessitating complicated
      setups and operations, and thus, it can be a useful tool for general biological
      experiments including cell-based disease diagnosis, stem cell engineering, and
      cellular physiological studies. 

PMID- 23875608
TI  - The efficacy of diabetic foot care education.
AB  - AIMS AND OBJECTIVES: To survey the efficacy of education about factors that
      influence the learning process and behaviour of diabetics following a nursing
      interventional project in diabetic foot care education. BACKGROUND: Educating
      diabetics can change their behaviour, which may contribute to the prevention of
      diabetic foot ulcer and amputation. However, there is little information on the
      factors that contribute to effectiveness of foot care education. DESIGN: Survey.
      METHODS: The data before education were collected by using structured assessment
      based on a practical reasoning scheme. The interventional diabetic foot care
      education project immediately followed. We used verbal and written patient
      education material. After education (six months), we used a questionnaire by
      postadministration. The data were analysed using content analysis, descriptive
      statistics and inferential statistics. RESULTS: We discovered a rise of
      knowledge, willingness and motivation to learn and to change the behaviour of
      diabetics after education. The clinical parameters (weight, Body Mass Index,
      blood pressure) demonstrated a statistically significant positive change six
      months after education. CONCLUSION: The findings after education show a rise in
      knowledge, willingness and motivation, which are important factors that
      contribute to changing behaviour of diabetics in diabetic foot care. After
      education, we identified better results in terms of weight and blood pressure,
      both of which play a role in the prevention of diabetic ulcer. RELEVANCE TO
      CLINICAL PRACTICE: The education valuable tool ensures knowledge, motivation and
      willingness to change behaviour in order to prevent diabetic foot complications
      of diabetics. By using structured assessment, nurses are able to modify their
      educational interventions.

PMID- 23875609
TI  - Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions
      onto alcohols.
AB  - Inspired by the extraordinary selectivities of acylases, we envisioned the use of
      lipophilic oligopeptidic organocatalysts for the acylative kinetic
      resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we
      describe in a full account the discovery and development process from the
      theoretical concept to the final catalyst, including scope and limitations.
      Competition experiments with various alcohols and electrophiles show the full
      potential of the employed oligopeptides. Additionally, we utilized NMR and IR
      spectroscopic methods as well as computations to shed light on the factors
      responsible for the selectivity. The catalyst system can be readily modified to a
      multicatalyst by adding other catalytically active amino acids to the peptide
      backbone, enabling the stereoselective one-pot synthesis of complex molecules
      from simple starting materials. 

PMID- 23875610
TI  - Social and structural risks for HIV among migrant and immigrant men who have sex
      with men in Moscow, Russia: implications for prevention.
AB  - Moscow has a large population of immigrants and migrants from across the Former
      Soviet Union. Little is studied about men who have sex with men (MSM) within
      these groups. Qualitative research methods were used to explore identities,
      practices, and factors affecting HIV prevention and risks among immigrant/migrant
      MSM in Moscow. Nine interviews and three focus group discussions were conducted
      between April-June 2010 with immigrant/migrant MSM, analyzed as a subset of a
      larger population of MSM who participated in qualitative research (n=121).
      Participants were purposively selected men who reported same sex practices (last
      12 months). Migrants were men residing in Moscow but from other Russian regions
      and immigrants from countries outside of Russia. A socioecological framework was
      used to describe distal to proximal factors that influenced risks for HIV
      acquisition. MSM ranged from heterosexual to gay-identified. Stigma and violence
      related to homophobia in homelands and concerns about xenophobia and distrust of
      migrants in Moscow were emerged as key themes. Participants reported greater
      sexual freedom in Moscow but feared relatives in homelands would learn of
      behaviors in Moscow, often avoiding members of their own ethnicity in Moscow.
      Internalized homophobia was prevalent and linked to traditional sexual views.
      Sexual risks included sex work, high numbers of partners, and inconsistent condom
      use. Avoidance of HIV testing or purchasing false results was related to
      reporting requirements in Russia, which may bar entry or expel those testing
      positive. HIV prevention for MSM should consider immigrant/migrant populations,
      the range of sexual identities, and risk factors among these men. The willingness
      of some men to socialize with immigrants/migrants of other countries may provide
      opportunities for peer-based prevention approaches. Immigrants/migrants comprised
      important proportions of the MSM population, yet are rarely acknowledged in
      research. Understanding their risks and how to reach them may improve the overall
      impact of prevention for MSM and adults in Russia.

PMID- 23875611
TI  - Long-term remission of folliculitis decalvans after treatment with the long
      pulsed Nd:YAG laser.
AB  - Folliculitis decalvans (FD) is a rare inflammatory scalp disorder presenting with
      tufted folliculitis, follicular papules and pustules, progressing to cicatricial
      alopecia. Current treatments mainly consist of antibiotic and immunomodulatory
      therapies and are often disappointing. FD has previously shown to respond to
      treatment with neodymium:yttrium aluminium garnet (Nd:YAG) laser in one case. We
      present a case of recalcitrant FD, successfully treated with a long-pulsed Nd:YAG
      laser. 

PMID- 23875612
TI  - A slender tract of glycine residues is required for translocation of the VP2
      protein N-terminal domain through the parvovirus MVM capsid channel to initiate
      infection.
AB  - Viruses constitute paradigms to study conformational dynamics in
      biomacromolecular assemblies. Infection by the parvovirus MVM (minute virus of
      mice) requires a conformational rearrangement that involves the intracellular
      externalization through capsid channels of the 2Nt (N-terminal region of VP2). We
      have investigated the role in this process of conserved glycine residues in an
      extended glycine-rich tract located immediately after 2Nt. Based on the virus
      structure, residues with hydrophobic side chains of increasing volume were
      substituted for glycine residues 31 or 33. Mutations had no effect on capsid
      assembly or stability, but inhibited virus infectivity. All mutations, except
      those to alanine residues which had minor effects, impaired 2Nt externalization
      in nuclear maturing virions and in purified virions, to an extent that correlated
      with the side chain size. Different biochemical and biophysical analyses were
      consistent with this result. Importantly, all of the tested glycine residue
      replacements impaired the capacity of the virion to initiate infection, at ratios
      correlating with their restrictive effects on 2Nt externalization. Thus small
      residues within the evolutionarily conserved glycine-rich tract facilitate 2Nt
      externalization through the capsid channel, as required by this virus to initiate
      cell entry. The results demonstrate the exquisite dependence on geometric
      constraints of a biologically relevant translocation event in a biomolecular
      complex. 

PMID- 23875613
TI  - A 55-mm object inside a 40-mm orbit.
AB  - A 43-year-old man was struck in the left orbit with his board while surfing and
      sustained a 3-cm laceration above his left eyebrow. The laceration was sutured
      closed primarily at a local emergency room. When he presented to UCSD
      oculoplastics for suture removal, he complained of diplopia with upgaze and was
      found to have hypoglobus on clinical exam. An orbital CT demonstrated a
      hyperintense linear signal within the orbit. The patient underwent surgical
      exploration. A 55-mm-length piece of fiberglass from the patient's surfboard was
      removed from his orbit. This case demonstrates the importance of having a high
      index of suspicion for retained orbital foreign bodies, regardless of the size of
      the object inflicting the injury.

PMID- 23875615
TI  - Drying of a charge-stabilized colloidal suspension in situ monitored by vertical
      small-angle X-ray scattering.
AB  - We report a first application of vertical small-angle X-ray scattering to
      investigate the drying process of a colloidal suspension by overcoming gravity
      related restrictions. From the observation of the drying behavior of charge
      stabilized colloidal silica in situ, we find the solidification of the colloidal
      particles exhibits an initial ordering, followed by a sudden aggregation when
      they overcome an electrostatic energy barrier. The aggregation can be driven not
      only by capillary pressure but also by thermal motion of the particles. The
      dominating contribution is determined by the magnitude of the energy barrier at
      the transition, which significantly decreases during drying due to an increased
      ionic strength. 

PMID- 23875616
TI  - Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA
      nanoparticles: part I. Effect of process variables on the mean size.
AB  - PLGA (poly d,l-lactic-co-glycolic acid) nanoparticles (NPs) encapsulating
      magnetite nanoparticles (MNPs) along with a model drug human serum albumin (HSA)
      were prepared by double emulsion solvent evaporation method. This Part I will
      focus on size and size distribution of prepared NPs, whereas encapsulation
      efficiency will be discussed in Part II. It was found that mean hydrodynamic
      particle size was influenced by five important process variables. To explore
      their effects, a five-factorial, three-level experimental design and statistical
      analysis were carried out using STATISTICA(r) software. Effect of process
      variables on the mean size of nanoparticles was investigated and finally
      conditions to minimize size of NPs were proposed. GAMSTM/MINOS software was used
      for optimization. The mean hydrodynamic size of nanoparticles ranged from 115 to
      329 nm depending on the process conditions. Smallest possible mean particle size
      can be achieved by using low polymer concentration and high dispersion energy
      (enough sonication time) along with small aqueous/organic volume ratio.

PMID- 23875614
TI  - Clinical applications of exercise stress echocardiography in the treadmill with
      upright evaluation during and after exercise.
AB  - Exercise stress echocardiography is the most frequently used stress test in our
      laboratory. Exercise echocardiography is used mainly in the study of patients
      with coronary artery disease. However, the technique is increasingly being used
      to study other diseases. In our centre, we use an original methodology, published
      by us in 2000, in which we evaluate heart function during exercise in the
      treadmill. After the exercise, patients are maintained in orthostatic position
      when appropriate or lying down in left lateral decubitus for further evaluation.
      Since this method seems to increase the quality and the quantity of information
      obtained in so many clinical arenas, we now present a detailed review of this
      methodology and its applications.

PMID- 23875617
TI  - Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA
      nanoparticles: part II. Effect of process variables on protein model drug
      encapsulation efficiency.
AB  - This study investigates encapsulation efficiency of model drug, encapsulated by
      magnetic poly d,l-lactic-co-glycolic acid (PLGA) nanoparticles (NPs). This is the
      following part of our preceding paper, which is referred in this paper as Part I.
      Magnetic nanoparticles and model drug human serum albumin (HSA)-loaded PLGA NPs
      were prepared by the double emulsion solvent evaporation method. Among five
      important process variables, concentration of PLGA and concentration of HSA in
      the inner aqueous phase along with their cross-effect had the strongest influence
      on the encapsulation efficiency. Encapsulation efficiency of nanoparticles ranged
      from 18% to 97% depending on the process conditions. Higher encapsulation
      efficiencies can be achieved by using low HSA and high PLGA concentrations. The
      optimization process, carried out by exact mathematical tools using GAMSTM/MINOS
      software makes it easier to find out optimum process conditions to achieve
      comparatively high encapsulation efficiency (e.g. 92.3%) for relatively small
      sized PLGA NPs (e.g. 155 nm).

PMID- 23875618
TI  - Microbial communities in flowback water impoundments from hydraulic fracturing
      for recovery of shale gas.
AB  - Hydraulic fracturing for natural gas extraction from shale produces waste brine
      known as flowback that is impounded at the surface prior to reuse and/or
      disposal. During impoundment, microbial activity can alter the fate of metals
      including radionuclides, give rise to odorous compounds, and result in
      biocorrosion that complicates water and waste management and increases production
      costs. Here, we describe the microbial ecology at multiple depths of three
      flowback impoundments from the Marcellus shale that were managed differently. 16S
      rRNA gene clone libraries revealed that bacterial communities in the untreated
      and biocide-amended impoundments were depth dependent, diverse, and most similar
      to species within the taxa gamma-proteobacteria, alpha-proteobacteria, delta
      proteobacteria, Clostridia, Synergistetes, Thermotogae, Spirochetes, and
      Bacteroidetes. The bacterial community in the pretreated and aerated impoundment
      was uniform with depth, less diverse, and most similar to known iodide-oxidizing
      bacteria in the alpha-proteobacteria. Archaea were identified only in the
      untreated and biocide-amended impoundments and were affiliated to the
      Methanomicrobia class. This is the first study of microbial communities in
      flowback water impoundments from hydraulic fracturing. The findings expand our
      knowledge of microbial diversity of an emergent and unexplored environment and
      may guide the management of flowback impoundments. 

PMID- 23875619
TI  - Predictive score for estimating cancer after venous thromboembolism: a cohort
      study.
AB  - BACKGROUND: Venous thromboembolism (VTE) has been associated with a higher risk
      of developing malignancy and mortality, and patients with VTE may therefore
      benefit from increased surveillance. We aimed to construct a clinical predictive
      score that could classify patients with VTE according to their risk for
      developing these outcomes. METHODS: Observational cohort study using an existing
      clinical registry in a tertiary academic teaching hospital in Buenos Aires,
      Argentina. 1264 adult patients greater than 17 years of age presented new VTE
      between June 2006 and December 2011 and were included in the registry. We
      excluded patients with previous or incident cancer, those who died during the
      first month, and those with less than one year of follow up (< 5%). 540 patients
      were included. Primary outcome was new cancer diagnosis during one year of follow
      up, secondary composite outcome was any new cancer diagnosis or death. The score
      was developed using a multivariable logistic regression model to predict cancer
      or death. RESULTS: During follow-up, one-quarter (26.4%) of patients developed
      cancer (9.2%) or died (23.7%). Patients with the primary outcome had more
      comorbidities, were more likely to have previous thromboembolism and less likely
      to have recent surgery. The final score developed for predicting cancer alone
      included previous episode of VTE, recent surgery and comorbidity (Charlson
      comorbidity score), [AUC of 0.75 (95% CI 0.66-0.84) and 0.79 (95% CI 0.63-0.95)
      in the derivation and validation cohorts, respectively]. The version of this
      score developed to predict cancer or death included age, albumin level,
      comorbidity, previous episode of VTE, and recent surgery [AUC = 0.72 (95% CI 0.66
      0.78) and 0.71 (95% CI 0.63-0.79) in the derivation and validation cohorts,
      respectively]. CONCLUSIONS: A simple clinical predictive score accurately
      estimates patients' risk of developing cancer or death following newly diagnosed
      VTE. This tool could be used to help reassure low risk patients, or to identify
      high-risk patients that might benefit from closer surveillance and additional
      investigations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01372514.

PMID- 23875620
TI  - Enhanced catalytic activity through the tuning of micropore environment and
      supercritical CO2 processing: Al(porphyrin)-based porous organic polymers for the
      degradation of a nerve agent simulant.
AB  - An Al(porphyrin) functionalized with a large axial ligand was incorporated into a
      porous organic polymer (POP) using a cobalt-catalyzed acetylene trimerization
      strategy. Removal of the axial ligand afforded a microporous POP that is
      catalytically active in the methanolysis of a nerve agent simulant. Supercritical
      CO2 processing of the POP dramatically increased the pore size and volume,
      allowing for significantly higher catalytic activities. 

PMID- 23875622
TI  - GZ-793A, a lobelane analog, interacts with the vesicular monoamine transporter-2
      to inhibit the effect of methamphetamine.
AB  - (R)-3-[2,6-cis-Di(4-methoxyphenethyl)piperidin-1-yl]propane-1,2-diol (GZ-793A)
      inhibits methamphetamine-evoked dopamine release from striatal slices and
      methamphetamine self-administration in rats. GZ-793A potently and selectively
      inhibits dopamine uptake at the vesicular monoamine transporter-2 (VMAT2). This
      study determined GZ-793A's ability to evoke [3H]dopamine release and inhibit
      methamphetamine-evoked [3H]dopamine release from isolated striatal synaptic
      vesicles. Results show GZ-793A concentration-dependent [3H]dopamine release;
      nonlinear regression revealed a two-site model of interaction with VMAT2 (High-
      and Low-EC50 = 15.5 nM and 29.3 MUM, respectively). Tetrabenazine and reserpine
      completely inhibited GZ-793A-evoked [3H]dopamine release, however, only at the
      High-affinity site. Low concentrations of GZ-793A that interact with the
      extravesicular dopamine uptake site and the High-affinity intravesicular DA
      release site also inhibited methamphetamine-evoked [3H]dopamine release from
      synaptic vesicles. A rightward shift in the methamphetamine concentration
      response was evident with increasing concentrations of GZ-793A, and the Schild
      regression slope was 0.49 +/- 0.08, consistent with surmountable allosteric
      inhibition. These results support a hypothetical model of GZ-793A interaction at
      more than one site on the VMAT2 protein, which explains its potent inhibition of
      dopamine uptake, dopamine release via a High-affinity tetrabenazine- and
      reserpine-sensitive site, dopamine release via a Low-affinity tetrabenazine- and
      reserpine-insensitive site, and a low-affinity interaction with the
      dihydrotetrabenazine binding site on VMAT2. GZ-793A inhibition of the effects of
      methamphetamine supports its potential as a therapeutic agent for the treatment
      of methamphetamine abuse.

PMID- 23875624
TI  - Time to stabilisation of the cervical spine when supported by a pillow in side
      lying.
AB  - Currently, there is little information to guide consumers, retailers and health
      professionals about the length of time it takes for the cervical spine to
      stabilise when resting on a pillow. The aim of this study was to determine the
      time required to achieve stabilisation of the cervical spine when supported by a
      polyester pillow and innerspring mattress in side lying. Twenty-four asymptomatic
      females rested in a standardised side lying position during the capture of 3D
      data from markers placed over cervical landmarks. Time to stabilisation was
      assessed for each axis, each landmark and globally for each participant. A large
      variation in global stabilisation times was identified between participants;
      however, 70.8% of participants had stabilised by 15 min or earlier. Fifteen
      minutes is the best estimate of the time to stabilisation of the cervical spine
      for young females in a side lying position when resting on a polyester pillow.
      PRACTITIONER SUMMARY: This study aimed to determine the time required to achieve
      stabilisation of the cervical spine when supported by a polyester pillow and
      innerspring mattress in side lying. Through a laboratory study using 3D VICON(r)
      motion analysis technology, we identified that 70.8% of participants had
      stabilised by 15 min.

PMID- 23875623
TI  - Combining naltrexone and prazosin in a single oral medication decreases alcohol
      drinking more effectively than does either drug alone.
AB  - BACKGROUND: Naltrexone (NTX) is underutilized in clinical treatment settings
      because its efficacy is modest, and it is not effective for all alcoholics and,
      when it is effective, a significant number of alcoholics fail to maintain initial
      treatment gains and subsequently relapse to heavy drinking. This has slowed
      acceptance of NTX by the treatment community, and there is a clear need for
      additional treatments for alcoholism and alcohol use disorders. Given that NTX
      and prazosin can each reduce alcohol drinking in rats selectively bred for
      alcohol preference and high voluntary alcohol drinking (alcohol-preferring "P"
      rats), we tested whether a combination of NTX + prazosin is more effective in
      decreasing alcohol drinking than is either drug alone. METHODS: P rats were given
      access to a 15% (v/v) alcohol solution for 2 hours daily. Rats were fed NTX and
      prazosin, alone or in combination, prior to onset of the daily 2-hour alcohol
      access period for 4 weeks and the effect of drug treatment on alcohol and water
      intake was assessed. RESULTS: During the first week of treatment, neither a low
      dose of NTX, nor prazosin, was effective in decreasing alcohol intake when each
      drug was administered alone, but combining the 2 drugs in a single medication
      significantly reduced alcohol intake. The combination was as effective as was a
      higher dose of NTX. Using a low dose of NTX in combination with prazosin may
      reduce the potential for undesirable side effects early in treatment which, in
      turn, may improve patient compliance and result in a more successful outcome when
      NTX is used for treating alcoholism and alcohol use disorders. CONCLUSIONS:
      Combining low-dose NTX and prazosin in a single medication may be more useful
      than is either drug alone for treating both inpatient and outpatient alcoholics
      and heavy drinkers early in the treatment process.

PMID- 23875625
TI  - Short communication: Effectiveness at 48 weeks of switching from enfuvirtide to
      raltegravir in virologically suppressed multidrug-resistant HIV type 1-infected
      patients in a Brazilian cohort.
AB  - The effectiveness of switching from enfuvirtide to raltegravir in HIV-1-infected
      patients on a suppressive antiretroviral regimen has been poorly studied in the
      clinical practice of developing countries. We conducted a multicenter
      retrospective cohort study in HIV-1-infected, multidrug-experienced adults (>=18
      years old) with plasma HIV-1-RNA <400 copies/ml for at least 4 months on an
      enfuvirtide-containing therapy between 2005 and 2010, in whom the attending
      physician switched from enfuvirtide to raltegravir. Effectiveness endpoints were
      measured at week 48 after switch. Analyses were conducted on an intent-to-treat
      basis and two strategies for handling missing outcome data were used (hereafter,
      strategies 1 and 2). Overall, 87 patients were eligible for analysis. At
      baseline, the median CD4(+) T cell count was 400 cells/MUl and 91.9% of patients
      had <50 HIV-1-RNA copies/ml. At week 48, the proportions of patients with plasma
      HIV-1-RNA <50 and <400 copies/ml were, respectively, 86.2% (95% CI=77.1; 92.7%)
      and 88.5% (95% CI=79.9; 94.3%) (strategies 1 and 2) and 89.7% (95% CI=81.3;
      95.2%) and 90.8% (95% CI=82.7; 95.9%) (strategies 1 and 2). This was a -10.3%
      (95% CI=-2.8; -17.9%) and -9.2% (95% CI=-2; -16.4%) difference from baseline in
      the proportion of patients with plasma HIV-1-RNA <400 copies/ml. The median
      increase in CD4(+) T cell counts was 41 and 64 cells/MUl (p<0.001) (strategies 1
      and 2). No patient withdrew raltegravir or developed opportunistic infections,
      but one was diagnosed with HIV-related dementia. In conclusion, switching from
      enfuvirtide to raltegravir in patients on a virologically suppressive regimen is
      an effective strategy even in a Brazilian clinical setting.

PMID- 23875626
TI  - Testosterone Restoration by Enclomiphene Citrate in Men with Secondary
      Hypogonadism: Pharmacodynamics and Pharmacokinetics.
AB  - OBJECTIVES: To determine the pharmacodynamic (PD) profile of serum total
      testosterone levels (TT) and luteinizing hormone (LH) in men with secondary
      hypogonadism following initial and chronic daily oral doses of enclomiphene
      citrate in comparison to transdermal testosterone. To determine the effects of
      daily oral doses of enclomiphene citrate (Androxal(r)) in comparison to
      transdermal testosterone on other hormones and markers in men with secondary
      hypogonadism. PATIENTS AND METHODS: This was a randomized, single blind, two
      center phase II study to evaluate three different doses of enclomiphene citrate
      (6.25mg, 12.5mg and 25 mg Androxal(r)), versus AndroGel(r), a transdermal
      testosterone, on 24-hour LH and TT in otherwise normal healthy men with secondary
      hypogonadism. Forty-eight men were enrolled in the trial (ITT Population), but 4
      men had T levels >350 ng/dL at baseline. Forty-four men completed the study per
      protocol (PP population). All subjects enrolled in this trial had serum TT in the
      low range (<350 ng/dL) and had low to normal LH (<12 IU/L) on at least two
      occasions. TT and LH levels were assessed each hour for 24 hours to examine the
      effects at each of three treatment doses of enclomiphene versus a standard dose
      (5 grams) of transdermal testosterone (AndroGel). In the initial profile TT and
      LH were determined in a naive population following a single initial oral or
      transdermal treatment (Day 1). This was contrasted to that seen after six weeks
      of continuous daily oral or transdermal treatment (Day 42). The pharmacokinetics
      of enclomiphene was performed in a select subpopulation. Serum samples were
      obtained over the course of the study to determine levels of various hormones and
      lipids. RESULTS: After six weeks of continuous use, the mean +/- SD concentration
      of TT at Day 42 C0hrTT, was 604 +/- 160 ng/dL for men taking the highest of dose
      of enclomiphene citrate (enclomiphene, 25 mg daily) and 500 +/- 278 ng in those
      men treated with transdermal testosterone. These values were higher than Day 1
      values but not different from each other (p = 0.23, T-test). All three doses of
      enclomiphene increased C0hrTT, CavgTT, CmaxTT, CminTT and CrangeTT. Transdermal
      testosterone also raised TT, albeit with more variability, and with suppressed LH
      levels. The patterns of TT over 24 hour period following six weeks of dosing
      could be fit to a non-linear function with morning elevations, mid-day troughs,
      and rising night-time levels. Enclomiphene and transdermal testosterone increased
      levels of TT within two weeks, but they had opposite effects on FSH and LH
      Treatment with enclomiphene did not significantly affect levels of TSH, ACTH,
      cortisol, lipids, or bone markers. Both transdermal testosterone and enclomiphene
      citrate decreased IGF-1 levels (p<0.05) but suppression was greater in the
      enclomiphene citrate groups. CONCLUSIONS: Enclomiphene citrate increased serum LH
      and TT; however, there was not a temporal association between the peak drug
      levels and the Cmax levels LH or TT. Enclomiphene citrate consistently increased
      serum TT into the normal range and increased LH and FSH above the normal range.
      The effects on LH and TT persisted for at least one week after stopping
      treatment.

PMID- 23875627
TI  - Structural barriers in the context of opiate substitution treatment in Germany--a
      survey among physicians in primary care.
AB  - BACKGROUND: Opiate substitution treatment (OST) is the most widely used treatment
      for opioid dependence in Germany with substantial long-term benefits for the
      patient and for society. Due to lessened restrictive admission criteria, the
      number of registered OST patients in Germany has increased continuously in the
      recent years, whereas the number of physicians providing OST has remained
      constant. Previous data already indicated a deteriorating situation in the
      availability or quality of OST delivered and that structural barriers impede
      physicians in actively providing OST. The present survey among a sample of
      primary care physicians in Germany aimed to identify and assess potential
      structural barriers for the provision of health care in the context of OST.
      METHODS: An anonymous written questionnaire was sent out to a sample of 2,332
      physicians across Germany providing OST. Physicians contacted were identified
      through databases of the Federal State Chambers of Physicians and/or of the
      Federal Associations of Statutory Health Insurance Physicians. Data obtained were
      analysed descriptively. RESULTS: The response rate was 25.5% and the majority of
      596 physicians sampled viewed substantial problems in terms of the regulatory
      framework of OST care in the German context. Furthermore, financial remuneration,
      insufficient qualification, as well as inadequate interdisciplinary cooperation
      in the treatment of comorbidities of opiate substituted patients were regarded as
      problematic. The number of physicians providing OST in Germany is expected to
      substantially decrease in the near future. CONCLUSION: Despite less restrictive
      admission criteria for OST in Germany, the legal regulation framework for OST is
      still a limiting factor through raising concerns on the provider and consumer
      side to be unable to adhere to the strict rules. To avoid future shortages in the
      provision of OST care on the system level in Germany, revisions to the legal
      framework seem to be necessary. In regards to adequate care for drug use-related
      infectious diseases and psychiatric comorbidities commonly found in opiate
      substituted patients, efforts are required to improve professional qualifications
      of physicians providing OST as well as respective interdisciplinary
      collaboration.

PMID- 23875628
TI  - Omacetaxine mepesuccinate (synribo) - newly launched in chronic myeloid leukemia.
AB  - INTRODUCTION: Omacetaxine mepesuccinate (formerly known as homoharringtonine
      [HHT]) is a natural alkaloid with significant anticancer activity partly through
      inhibition of protein synthesis and induction of apoptosis. Prior to the
      development of tyrosine kinase inhibitors (TKIs), HHT was the most active therapy
      in chronic myeloid leukemia (CML) after interferon failure. Subsequent trials
      showed that HHT and omacetaxine are active in patients failing several TKIs or
      carrying the T315I mutation. AREAS COVERED: This review will discuss the
      preclinical development of HHT and omacetaxine mepesuccinate in CML and the
      clinical studies leading to its approval by the Food and Drug Administration
      (FDA). EXPERT OPINION: A sizable number of patients with CML will develop TKI
      resistance, frequently through the acquisition of BCR-ABL1 kinase domain
      mutations. Omacetaxine is active in patients with CML after failure to multiple
      TKIs and in those carrying the T315I mutation, which is highly resistant to all
      FDA-approved TKIs except for ponatinib. Both ponatinib and omacetaxine have been
      recently approved by the FDA and represent useful treatment options for patients
      with CML who failed several TKIs and/or acquired the T315I mutation. The
      development of an oral formulation of omacetaxine would greatly facilitate its
      use and provide an attractive option for TKI-based combinatorial strategies.

PMID- 23875629
TI  - Two case presentations of profound labial edema as a presenting symptom of
      hypermobility-type Ehlers-Danlos syndrome.
AB  - INTRODUCTION: Hypermobility-type Ehlers-Danlos syndrome (EDS), an often-missed
      diagnosis with the potential for serious sequelae, may have a variety of uncommon
      presentations, some of which may be gynecologic. AIM: The aim of this case report
      is to present two cases of profound labial edema associated with intercourse as a
      presenting symptom of hypermobility-type EDS. METHODS: A 25-year-old female
      presented with severe labia minora swelling and bladder pressure associated with
      intercourse, in addition to persistent genital arousal. History revealed easy
      bruising, joint pain, and family history of aneurysm. A 22-year-old female
      presented with intermittent profound labial swelling for 6 years, associated with
      sensitivity and pain with intercourse. The patient has a history of joint pain
      and easy bruising, as well a sister with joint hypermobility and unexplained
      lymphedema. The presenting symptom of profound labial edema led to the diagnosis
      of hypermobility-type EDS. RESULTS: Patients with hypermobility syndrome exhibit
      an increased ratio of type III collagen to type I collagen, causing tissue laxity
      and venous insufficiency. Abnormal collagen may lead to gynecologic
      manifestations, including unexplained profound labial edema, pelvic organ
      prolapse in the absence of risk factors, and possibly persistent genital arousal.
      CONCLUSIONS: This case report highlights the need for further research to
      determine incidence of labial edema in hypermobility-type EDS and to further
      elucidate a potential correlation between profound labial edema and collagen
      disorders.

PMID- 23875630
TI  - Photoinduced and N-bromosuccinimide-mediated cyclization of 2-azido-N
      phenylacetamides.
AB  - An efficient synthesis of quinoxalin-2(1H)-ones or spiro[cyclohexene-1,2'
      imidazol]-4'-ones has been achieved in moderate to high yields by the visible
      light-induced and N-bromosuccinimide-mediated cyclization reaction of 2-azido-N
      phenylacetamides at ambient temperature. Both the regioselectivity and the speed
      of cyclization are affected by the substituents attached to the phenyl ring. For
      example, quinoxalin-2-ones are produced as the main products when the substrates
      bear electron-withdrawing groups at the para-position of the phenyl ring; in
      contrast, spiro[cyclohexene-1,2'-imidazol]-4'-ones are obtained as the main
      products when the substrates bear electron-donating groups at the para-position. 

PMID- 23875631
TI  - Computational prediction of one-electron reduction potentials and acid
      dissociation constants for guanine oxidation intermediates and products.
AB  - Reduction potentials and pK(a) values were calculated for intermediates and
      products along three major pathways for guanine oxidation using the B3LYP and CBS
      QB3 levels of theory with the SMD implicit solvation model. N-methylated
      nucleobases were used as models for nucleoside species. Ensemble averaged
      reduction potentials at pH 7 (E7) were obtained by combining calculated standard
      reduction potentials with calculated pKa values in addition to accounting for
      tautomerization energies. Calculated pK(a) values are reasonable based on
      experimental estimates and chemical intuition. Pathway A leads to
      guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp). The first step is the
      oxidation of 8-oxoguanine which proceeds by the loss of an electron followed by
      the loss of two protons and loss of another electron, yielding 8-oxopurine. The
      calculated E7 values for the remaining intermediates and products are at least
      0.3 V higher than that of guanine, indicating that further oxidation of these
      species is unlikely. Pathway B leads to two formamidopyrimidine isomers (FAPyG
      and 2,5FAPyG). Species along this pathway have calculated reduction potentials
      that are much lower than the oxidation potential for guanine and would likely be
      very short-lived in an oxidatively stressed environment. Pathway C leads to
      reduced spiroiminodihydantoin and 5-carboxamido-5-formamido-2-iminohydantoin
      (2Ih). Similar to pathway A, the calculated reduction potentials for species
      along this pathway are at least 0.4 V higher than that of guanine.

PMID- 23875632
TI  - Probing the hexosamine biosynthetic pathway in human tumor cells by multitargeted
      tandem mass spectrometry.
AB  - Cancer progression is accompanied by increases in glucose and glutamine
      metabolism, providing the carbon and nitrogen required in downstream anabolic
      pathways. Fructose-6P, glutamine, and acetyl-CoA are central metabolites and
      substrates of the hexosamine biosynthesis pathway (HBP) to UDP-N
      acetylglucosamine (UDP-GlcNAc), an essential high-energy donor for protein
      glycosylation. Golgi and cytosolic glycosylation pathways are sensitive to UDP
      GlcNAc levels, which in turn regulates metabolic homeostasis in a poorly
      understood manner. To study the hexosamine biosynthesis pathway in cancer cells,
      we developed a targeted approach for cellular metabolomics profiling by liquid
      chromatography-tandem mass spectrometry. Human cervical (HeLa) and prostate
      cancer (PC-3) cell lines were cultured in medium with increasing concentrations
      of glucose, glutamine, or GlcNAc to perturb the metabolic network. Principal
      component analysis indicated trends that were further analyzed as individual
      metabolites and pathways. HeLa cell metabolism was predominantly glycolytic,
      while PC-3 cells showed a greater dependency on extracellular glutamine. In both
      cell lines, UDP-GlcNAc levels declined with glucose but not glutamine starvation,
      whereas glutamine abundance increased UDP-GlcNAc levels 2-3-fold. GlcNAc
      supplementation increased UDP-GlcNAc 4-8-fold in both HeLa and PC-3 cells. GlcNAc
      supplementation in HeLa cells induced nonmonotonic changes in NADH/NAD+,
      NADPH/NADP+, reactive oxygen species, and reduced/oxidized glutathione. In PC-3
      cells, GlcNAc supplementation also increased glucose and glutamine uptake and
      catabolism. Our results suggest that stimulation of the HBP in cancer cells
      regulates metabolism and redox potential, which might be exploited to target
      cancer cells. 

PMID- 23875633
TI  - Education and Imaging. Gastrointestinal: Hepatodiaphragmatic interposition of
      small bowel loop: a rare cause of Chilaiditi's syndrome.

PMID- 23875634
TI  - Education and Imaging. Gastrointestinal: Capsule endoscopy of a very refractory
      celiac disease.

PMID- 23875635
TI  - Education and Imaging. Gastrointestinal: Unusual duodenal follicular lymphoma
      observed by magnifying endoscopy with narrow-band imaging.

PMID- 23875636
TI  - Education and Imaging. Hepatobiliary and pancreatic: Duodenal bleeding from a
      hepatic artery aneurysm.

PMID- 23875637
TI  - Education and Imaging. Hepatobiliary and pancreatic: Portal hypertensive
      biliopathy presenting as acute cholangitis.

PMID- 23875639
TI  - Lung function and plasma fibrinogen concentrations in the Newcastle Thousand
      Families birth cohort between age 49 and 51 years.
AB  - BACKGROUND AND OBJECTIVE: A number of studies have suggested inverse associations
      between lung function and inflammatory markers, including fibrinogen. In this
      study, we used data from the Newcastle Thousand Families birth cohort to assess
      the association between contemporaneous markers of lung function and fibrinogen
      while adjusting for potential confounding factors throughout life. METHODS: At
      age 49-51 years, complete data on lung function and plasma fibrinogen were
      available for 380 study members. These data were analysed in relation to each
      other, adjusted for sex and height, with further adjustment for potential
      confounders within linear regression models using robust estimates. RESULTS:
      Forced expiratory volume in 1 s was significantly inversely associated with
      plasma fibrinogen concentration after initial adjustments for sex and height
      (beta = -0.12, P = 0.011) and remained so after further adjustments for pack
      years of cigarettes smoked and current smoking status. On further adjustment for
      standardized birthweight and duration breast-fed, the association approached
      statistical significance (P = 0.051). Adjusting for body mass index (BMI)
      resulted in a loss of significance (P = 0.09), but an unchanged regression
      coefficient, while, after adjustment for percent body fat, rather than BMI, the
      association was no longer significant (P = 0.20) and the coefficient reduced.
      CONCLUSIONS: The association between lung function and fibrinogen remains after
      adjustment for potential early-life confounders and smoking. However, it is not
      independent of contemporaneous measures of adiposity, with evidence of
      confounding by percent body fat. Further studies, with measures of adiposity, are
      required to confirm whether associations between markers of inflammation and lung
      function are due to residual confounding by adiposity.

PMID- 23875638
TI  - Association of N-acetyltransferase 2 and cytochrome P450 2E1 gene polymorphisms
      with antituberculosis drug-induced hepatotoxicity in Western India.
AB  - BACKGROUND AND AIM: Tuberculosis (TB) is a major public health problem in India.
      Despite the treatment availability and monitoring, drug-induced hepatotoxicity
      (DIH) is a serious concern and can lead to discontinuation of treatment. Anti-TB
      DIH is well known and can aggravate because of pharmacokinetic and
      pharmacodynamic interactions. Genetic polymorphism in the drug-metabolizing
      enzyme genes is an important factor that predisposes certain fraction of the
      population to drug-induced toxicity. The purpose of this study was to assess the
      association of N-acetyltransferase 2 (NAT2) and cytochrome P450 2E1 (CYP2E1) gene
      polymorphism with anti-TB DIH in Western Indian population. METHODS: A
      prospective cohort study of 215 patients taking treatment against TB was
      performed. The NAT2 and CYP2E1 genotypes were determined using polymerase chain
      reaction and restriction fragment length polymorphism methods. Logistic
      regression model was used to calculate odds ratio at 95% confidence interval and
      their respective P values. RESULTS: The risk of anti-TB DIH was significantly
      higher in slow acetylator (SA) than in intermediate and rapid acetylator of NAT2
      genotypes (odds ratio: 2.3, P = 0.01). We also observed the homozygous point
      mutation at position 481, associated with higher risk of hepatotoxicity (P <
      0.01). The major haplotype NAT2*4 seems to provide protection in DIH compared
      with non-DIH TB patients (P = 0.04). However, we did not find a significant
      association between CYP2E1 genotypes and anti-TB DIH. CONCLUSION: Increased
      susceptibility to isoniazid (INH)-induced hepatotoxicity due to presence of NAT2
      SA polymorphism was demonstrated in Western Indian population. NAT2 genotyping
      can therefore serve as an important tool for identifying patients predisposed to
      anti-TB DIH.

PMID- 23875640
TI  - Development of sheath-flow probe electrospray ionization mass spectrometry and
      its application to real time pesticide analysis.
AB  - For the real time and direct analysis of chemical constituents from living beings
      and dry sample, sheath-flow probe electrospray ionization mass spectrometry (SF
      PESI-MS) has been newly developed. The components from dry or semidry biological
      tissues can be extracted using the solvent and picked up by the needle for
      electrospray. This technique was applied to real-time pesticide analysis of
      living plants. The results have been validated with that of a well-known system,
      liquid extraction surface analysis mass spectrometry (LESA-MS). It is
      demonstrated that SF-PESI-MS can produce reasonable ionization efficiency, which
      is confirmed by LESA-MS. 

PMID- 23875641
TI  - Pressure-assisted selective preconcentration in a straight nanochannel.
AB  - We investigate the preconcentration profiles of a fluorescein and bovine serum
      albumin derivatized with this fluorescent tag in a microfluidic chip bearing a
      nanoslit. A new preconcentration method in which a hydrodynamic pressure is added
      to both electroosmotic and electrophoretic contributions is proposed to monitor
      the location of the preconcentration frontline. A simple predictive model of this
      pressure-assisted electropreconcentration is proposed for the evolution of the
      flow profile along this micro/nano/microfluidic structure. We show with a small
      analyte such as fluorescein that the additional hydrostatic pressure mode enables
      to stabilize the concentration polarization (CP) effect, resulting in better
      control of the cathodic focusing (CF) peak. For BSA (bovine serum albumin), we
      exhibit that the variation of the hydrodynamic pressure can have an even more
      drastic effect on the preconcentration. We show that, depending on this
      hydrodynamic pressure, the preconcentration can be chosen, either in the cathodic
      side or in the anodic one. For the first time, we prove here that both anodic
      focusing (AF) and cathodic focusing (CF) regimes can be reached in the same
      structures. These results also open new routes for the detection and the
      quantification of low abundance biomarkers. 

PMID- 23875642
TI  - A thymine tetrad assembly templated from thymidylic acid.
AB  - A template tetra-coupled with thymidylic acid through a phosphate linkage was
      characterized in methanol for emergent properties of nucleobase tetrad formation.
      Intramolecular hydrogen bonded base pairing in the absence of a cation was
      indicated for the thymidylic acid species supporting a monomeric template
      assembled structure. Thus, an initial report of a stabilized individual thymine
      tetrad assembly is presented here. Consistent with previous investigations, a
      deoxyguanylic acid variant templated an analogous methanolic monomeric G-tetrad
      in comparison to the thymine species. 

PMID- 23875643
TI  - Location of the zygomatico-orbital foramen on the inferolateral orbital wall:
      clinical implications.
AB  - PURPOSE: To describe the location of the zygomatico-orbital foramen on the
      inferolateral orbital wall. METHODS: This anatomic study examined 28 orbits of 14
      dry human adult skulls. The zygomatico-orbital foramen was identified by passing
      a thin wire from the zygomatico-facial foramen to its orbital aspect and a thin
      flexible ruler was used to measure 1) the distance perpendicular to the closest
      point on the inferior orbital rim, 2) the distance from the inferior orbital
      fissure, and 3) the distance from the area used for retrobulbar injections.
      RESULTS: The mean distance from the zygomatico-orbital foramen to the closest
      point on the inferior orbital rim was 4.7 mm (range from 1 to 7 mm). The mean
      distance from the inferior orbital fissure was 14.9 mm (range from 10 to 18 mm).
      The mean distance from the area of retrobulbar injection was 6.0 mm (range from 3
      to 10 mm). CONCLUSIONS: The location of the zygomatico-orbital foramen within the
      inferolateral orbit is quite variable. This is the first study to attempt to
      quantify its proximity to the site of retrobulbar injection. We conclude that it
      is an important anatomical structure to consider when giving retrobulbar
      anesthesia, especially given the variability in technique among ophthalmologists.

PMID- 23875644
TI  - Characterization of permeability of electrospun yarns.
AB  - We developed a novel technique enabling determination of the permeability of
      electrospun yarns composed of hundreds of fibers. Analyzing the wicking kinetics
      in a yarn-in-a-tube composite conduit, it was found that the kinetic is very
      specific. The liquid was pulled by the capillary pressure associated with the
      meniscus in the tube while the main resistance comes from the yarn. Therefore,
      one can separate the yarn permeability from the capillary pressure, which cannot
      be done in wicking experiments with single yarns. A surface tensiometer (Cahn)
      was employed to collect the data on wicking kinetics of hexadecane into the yarn
      in-a-tube conduits. Yarns from different polymers and blends were electrospun and
      characterized using the proposed protocol. We showed that the permeability of
      electrospun yarns can be varied in a broad range from 10(-14) m(2) to 10(-12)
      m(2) by changing the fiber diameter and packing density. These results offer new
      applications of electrospun yarns as flexible micro- and nanofluidic systems. 

PMID- 23875645
TI  - Hormonal control of stem cell systems.
AB  - Many organs respond to physiological challenges by changing tissue size or
      composition. Such changes may originate from tissue-specific stem cells and their
      supportive environment (niche). The endocrine system is a major effector and
      conveyor of physiological changes and as such could alter stem cell behavior in
      various ways. In this review, we examine how hormones affect stem cell biology in
      four different organs: the ovary, intestine, hematopoietic system, and mammary
      gland. Hormones control every stage of stem cell life, including establishment,
      expansion, maintenance, and differentiation. The effects can be cell autonomous
      or non-cell autonomous through the niche. Moreover, a single hormone can affect
      different stem cells in different ways or affect the same stem cell differently
      at various developmental times. The vast complexity and diversity of stem cell
      responses to hormonal cues allow hormones to coordinate the body's reaction to
      physiological challenges. 

PMID- 23875646
TI  - Microtubule-depolymerizing kinesins.
AB  - The microtubule (MT) cytoskeleton supports a broad range of cellular functions,
      from providing tracks for intracellular transport, to supporting movement of
      cilia and flagella, to segregating chromosomes in mitosis. These functions are
      facilitated by the organizational and dynamic plasticity of MT networks. An
      important class of enzymes that alters MT dynamics is the depolymerizing kinesin
      like proteins, which use their catalytic activities to regulate MT end dynamics.
      In this review, we discuss four topics surrounding these MT-depolymerizing
      kinesins. We provide a historical overview of studies focused on these motors and
      discuss their phylogeny. In the second half, we discuss their enzymology and
      biophysics and give an overview of their known cellular functions. This
      discussion highlights the fact that MT-depolymerizing kinesins exhibit a diverse
      range of design principles, which in turn increases their functional versatility
      in cells. 

PMID- 23875647
TI  - GTP-dependent membrane fusion.
AB  - Shape changes and topological remodeling of membranes are essential for the
      identity of organelles and membrane trafficking. Although all cellular membranes
      have common features, membranes of different organelles create unique
      environments that support specialized biological functions. The endoplasmic
      reticulum (ER) is a prime example of this specialization, as its lipid bilayer
      forms an interconnected system of cisternae, vesicles, and tubules, providing a
      highly compartmentalized structure for a multitude of biochemical processes. A
      variety of peripheral and integral membrane proteins that facilitate membrane
      curvature generation, fission, and/or fusion have been identified over the past
      two decades. Among these, the dynamin-related proteins (DRPs) have emerged as key
      players. Here, we review recent advances in our functional and molecular
      understanding of fusion DRPs, exemplified by atlastin, an ER-resident DRP that
      controls ER structure, function, and signaling. 

PMID- 23875648
TI  - Microtubules in cell migration.
AB  - Migration is a polarized cellular process that opposes a protrusive front edge to
      a retracting trailing edge. From the front to the rear, actin-mediated forces
      sequentially promote cell protrusion, adhesion, contraction, and retraction. Over
      the past decade, microtubules have revealed their pivotal role in cell migration.
      Through their roles in cell mechanics, intracellular trafficking, and signaling,
      microtubules participate in all essential events leading to cell migration. The
      front-rear polarization of microtubule functions relies on the asymmetric
      regulation of microtubule dynamics and stability; the asymmetric distribution of
      microtubule-associated protein complexes; and finally, the orientation of the
      microtubule network along the axis of migration. Microtubule network polarity
      controls the establishment and maintenance of the spatial and temporal
      coordination of migration events and is therefore the key to persistent directed
      migration. This review summarizes our current understanding of the functions of
      microtubules in persistent cell migration and of the migration-associated signals
      that promote microtubule network polarization. 

PMID- 23875650
TI  - Quality of life in China rural-to-urban female migrant factory workers: a before
      and-after study.
AB  - BACKGROUND: Rural-to-urban female migrant workers have a lower quality of life
      compared to the general population. Improving these conditions remains highly
      challenging. This paper reports the health-related quality of life (HRQoL) of the
      female migrant workers in an educational project. METHODS: In this before-and
      after study, a community-based health education intervention was developed to
      improve female migrant workers' HRQoL and job satisfaction. A factory was
      selected as the location to implement the trial, using a before-and-after design.
      The education intervention included distribution and free access to study
      materials, monthly lectures, and counseling. The primary endpoint was HRQoL, and
      gynecological disease and job satisfaction were secondary endpoints. We assessed
      HRQoL at baseline and at 6-month follow-up using the Health Survey Short Form (SF
      36). RESULTS: Compared to the baseline assessment, the participants at the 6
      month survey reported higher General Health scores (standardized-beta
      coefficients (Betas) of beta = 0.056; P <0.001), Vitality scores (beta = 0.066; P
      <0.001), Mental Health scores (beta = 0.062; P <0.001), mental component summary
      scores (beta = 0.040; P <0.001), and job satisfaction (Odds Ratio [OR] 2.104, 95%
      confidence interval [CI] 1.837-2.408; P <0.01). CONCLUSIONS: A community-based
      educational intervention, targeted at female migrant workers, appears effective
      in improving HRQoL and job satisfaction.

PMID- 23875651
TI  - Phosphatidylinositol is crucial for the mechanosensitivity of Mycobacterium
      tuberculosis MscL.
AB  - The bacterial mechanosensitive channel of large conductance (MscL) directly
      senses and responds to membrane tension. It serves as an "emergency release
      valve" upon acute decreases in the osmotic environment, thus preventing cell
      lysis. It is one of the best studied mechanosensitive channels and serves as a
      paradigm of how a channel senses and responds to its membrane environment. The
      MscL protein is highly conserved, found throughout the bacterial kingdom, and has
      been shown to encode a functional mechanosensitive channel in all species where
      it has been studied. However, channels from different species have shown some
      functional variance; an extreme example is the Mycobacterium tuberculosis MscL,
      which when heterologously expressed in Escherichia coli requires significantly
      more membrane tension for gating than the endogenous E. coli MscL. We previously
      speculated that the membrane environment or factors not found in E. coli promoted
      the proper gating of the M. tuberculosis MscL channel in its native environment.
      Here, by reconstituting the M. tuberculosis and E. coli MscL channels in various
      lipids, we demonstrate that inclusion of phosphatidylinositol, a lipid found in
      M. tuberculosis but not E. coli, is sufficient for gating of the M. tuberculosis
      MscL channel within a physiological range of membrane tension. 

PMID- 23875652
TI  - People's experiences of suffering a lower limb fracture and undergoing surgery.
AB  - AIMS AND OBJECTIVES: To describe people's experiences of suffering a lower limb
      fracture and undergoing surgery, from the time of injury through to the care
      given at the hospital and recovery following discharge. BACKGROUND: There is a
      lack of research on people's experiences of suffering a lower limb fracture and
      undergoing surgery - from injury to recovery. DESIGN: A qualitative approach was
      used. METHODS: Interviews with nine participants were subjected to thematic
      content analysis. RESULTS: One theme was expressed: from realising the
      seriousness of the injury to regaining autonomy. Participants described feelings
      of frustration and helplessness when realising the seriousness of their injury.
      The wait prior to surgery was a strain and painful experience, and participants
      needed orientation for the future. They expressed feelings of vulnerability about
      being in the hands of staff during surgery. After surgery, in the postanaesthesia
      unit, participants expressed a need to have control and to feel safe in their new
      situation. To mobilise and regain their autonomy was a struggle, and participants
      stated that their recovery was extended. CONCLUSIONS AND RELEVANCE TO CLINICAL
      PRACTICE: Participants found themselves in a new and unexpected situation and
      experienced pain, vulnerability and a striving for control during the process,
      that is, 'from realising the seriousness of the injury to regaining autonomy'.
      How this is managed depends on how the patient's needs are met by nurses. The
      nursing care received while suffering a lower limb fracture and undergoing
      surgery should be situation specific as well as individual specific. The safe
      performance of technical interventions and the nurse's comprehensive explanations
      of medical terms may help the patient to feel secure during the process.

PMID- 23875649
TI  - microRNA control of mouse and human pluripotent stem cell behavior.
AB  - In the past decade, significant progress has been made in understanding both
      microRNA function and cellular pluripotency. Here we review the intersection of
      these two exciting fields. While microRNAs are not required for the establishment
      and maintenance of pluripotency in early development and cell culture,
      respectively, they are critically important in the regulation of the cell cycle
      structure of pluripotent stem cells as well as the silencing of the pluripotency
      program upon differentiation. Pluripotent cells, both in vivo and in vitro,
      dominantly express a single family of microRNAs, which can promote the
      reprogramming of a somatic cell back to a pluripotent state. Here, we review the
      known mechanisms by which these and other microRNAs regulate the different
      aspects of the pluripotent stem cell program in both mouse and human. 

PMID- 23875654
TI  - The reduction in sigma-promoter recognition flexibility as induced by core RNAP
      is required for sigma to discern the optimal promoter spacing.
AB  - Sigma (sigma) factors are bacterial transcription initiation factors that direct
      transcription at cognate promoters. The promoters recognized by primary sigma are
      composed of -10 and -35 consensus elements separated by a spacer of 17+/-1 bp for
      optimal activity. However, how the optimal promoter spacing is sensed by the
      primary sigma remains unclear. In the present study, we examined this issue using
      a transcriptionally active Bacillus subtilis N-terminally truncated sigmaA
      (SND100-sigmaA). The results of the present study demonstrate that SND100-sigmaA
      binds specifically to both the -10 and -35 elements of the trnS spacing variants,
      of which the spacer lengths range from 14 to 21 bp, indicating that simultaneous
      and specific recognition of promoter -10 and -35 elements is insufficient for
      primary sigma to discern the optimal promoter spacing. Moreover, shortening in
      length of the flexible linker between the two promoter DNA-binding domains of
      sigmaA also does not enable SND100-sigmaA to sense the optimal promoter spacing.
      Efficient recognition of optimal promoter spacing by SND100-sigmaA requires core
      RNAP (RNA polymerase) which reduces the flexibility of simultaneous and specific
      binding of SND100-sigmaA to both promoter -10 and -35 elements. Thus the
      discrimination of optimal promoter spacing by sigma is core-dependent. 

PMID- 23875653
TI  - Coevolution analyses illuminate the dependencies between amino acid sites in the
      chaperonin system GroES-L.
AB  - BACKGROUND: GroESL is a heat-shock protein ubiquitous in bacteria and eukaryotic
      organelles. This evolutionarily conserved protein is involved in the folding of a
      wide variety of other proteins in the cytosol, being essential to the cell. The
      folding activity proceeds through strong conformational changes mediated by the
      co-chaperonin GroES and ATP. Functions alternative to folding have been
      previously described for GroEL in different bacterial groups, supporting enormous
      functional and structural plasticity for this molecule and the existence of a
      hidden combinatorial code in the protein sequence enabling such functions.
      Describing this plasticity can shed light on the functional diversity of GroEL.
      We hypothesize that different overlapping sets of amino acids coevolve within
      GroEL, GroES and between both these proteins. Shifts in these coevolutionary
      relationships may inevitably lead to evolution of alternative functions. RESULTS:
      We conducted the first coevolution analyses in an extensive bacterial phylogeny,
      revealing complex networks of evolutionary dependencies between residues in
      GroESL. These networks differed among bacterial groups and involved amino acid
      sites with functional importance and others with previously unsuspected
      functional potential. Coevolutionary networks formed statistically independent
      units among bacterial groups and map to structurally continuous regions in the
      protein, suggesting their functional link. Sites involved in coevolution fell
      within narrow structural regions, supporting dynamic combinatorial functional
      links involving similar protein domains. Moreover, coevolving sites within a
      bacterial group mapped to regions previously identified as involved in folding
      unrelated functions, and thus, coevolution may mediate alternative functions.
      CONCLUSIONS: Our results highlight the evolutionary plasticity of GroEL across
      the entire bacterial phylogeny. Evidence on the functional importance of
      coevolving sites illuminates the as yet unappreciated functional diversity of
      proteins.

PMID- 23875655
TI  - Genetically engineered Newcastle disease virus for prostate cancer: a magic
      bullet or a misfit.

PMID- 23875656
TI  - Improving urologic cancer care through telemedicine.

PMID- 23875658
TI  - Telemedical technologies in urological cancer care: past, present and future
      applications.
AB  - Since the initial development of telegraphy by Sir Charles Wheatstone in 1837 and
      the telephone by Alexander Graham Bell in 1875, doctors have been able to convey
      medical information across great distances. The exchange and sharing of medical
      information has evolved and adapted to suit the vast array of today's medicine.
      Early adopters of telemedicine within clinical practice have gained significant
      health economic benefits. The arrival of wireless connections has further
      enhanced the possibilities for all clinical work with focus on diagnosis,
      treatment and management of urological cancers, as highlighted in this article. 

PMID- 23875659
TI  - Accurate patient selection and multimodal treatment offer the best therapeutic
      option in high-risk prostate cancer.
AB  - High-risk prostate cancer (HRPC) has higher recurrence potential and multimodal
      treatment offers better outcomes in this population. The aim of this article is
      to comprehensively present the multimodal therapeutic options for HRPC. Review of
      the literature on HRPC with a literature selection based on evidence and
      practical considerations. Therapeutic options for localized HRPC are radio
      hormone therapy and radical prostatectomy with extended lymph node dissection.
      Selection of patients is essential to define individualized therapeutic strategy
      and timing for every modality should come as a consensus of medical supported
      evidence. Accurate patient selection and multimodal treatment offer the best
      therapeutic option in HRPC. 

PMID- 23875660
TI  - Current, new and novel therapy for castration-resistant prostate cancer.
AB  - Androgen deprivation therapy is the standard of care for the initial treatment of
      metastatic prostate cancer. However, the majority of these patients live long
      enough to experience disease progression despite castration. This scenario is
      defined as castration-resistant prostate cancer (CRPC) and has a poor outcome and
      limited options for treatment. First-line treatment after hormonal therapy
      failure include secondary hormonal manipulation and docetaxel. Advances in the
      understanding of the molecular mechanisms underlying CRPC have translated into a
      recent increase in the number of effective systemic agents, and some of them have
      been already approved as first and second-line treatment. Despite these advances,
      the median survival in the first-line setting of metastatic CRPC is approximately
      20 months and in the postdocetaxel setting is approximately 15 months. Promising
      and necessary new therapies in Phase III trials include hormonal agents, new
      cytotoxics agents, as well as other immunotherapeutics and antiprostate-specific
      membrane antigen therapies.

PMID- 23875661
TI  - Complications of prostate biopsy.
AB  - Biopsy of the prostate is a common procedure with minor complications that are
      usually self-limited. However, if one considers that millions of men undergo
      biopsy worldwide, one realizes that although complication rate is low, the number
      of patients suffering from biopsy complications should not be underestimated and
      can be a clinically relevant problem for healthcare professionals. In this
      review, the authors present diagnosis and management of postbiopsy of prostate
      complications. Bleeding is the most common complication observed after prostate
      biopsy, but the use of aspirin or nonsteroidal anti-inflammatory drugs is not an
      absolute contraindication to prostate biopsy. Emerging resistance to
      ciprofloxacin is the most probable cause of the increasing risk of infectious
      complications after prostate biopsy. Even though extremely rare, fatal
      complications are possible and were described in case reports. 

PMID- 23875662
TI  - Adjuvant therapy in node-positive vulvar cancer.
AB  - Due to an increasing incidence with concurrently decreasing age at onset, vulvar
      cancer represents a current challenge for gynecologic oncologists. Positive lymph
      nodes of the groins have been proven to be the most important prognostic factor
      for affected patients, significantly impairing overall survival. Distinct
      criteria for indication of adjuvant therapy following primary tumor resection and
      groin surgery are still under debate. At present, only patients with two or more
      positive lymph nodes are treated with adjuvant radiotherapy despite growing
      evidence that patients with only one nodal macrometastasis already have a
      significantly worse outcome and might benefit from adjuvant treatment. This
      review discusses existing evidence focusing on different therapeutic approaches
      and their potential indication in vulvar cancer. Based on the available data the
      need for future trials is being elaborated. 

PMID- 23875663
TI  - Prevention, identification and treatment of vulvar squamous (pre)malignancies: a
      review focusing on quality of care.
AB  - Vulvar squamous cell carcinoma, its precursor lesions (usual and differentiated
      vulvar intraepithelial neoplasia) and lichen sclerosus are rare diseases that may
      have a large impact on the lives of affected women and their partners. Proper
      identification is vital, but the lesions are sometimes difficult to diagnose
      because of their rarity and variety of symptoms. High quality of care and proper
      treatment is important in order to minimize the morbidity and mortality caused by
      these lesions. This review gives an outline of the latest insights regarding the
      current evidence in this area and unresolved issues. Additionally, it highlights
      the improvements that should be made in order to optimize prevention and
      identification of (pre-)malignant vulvar lesions and to increase the quality of
      care for these patients. 

PMID- 23875664
TI  - Current status of sentinel lymph node mapping in the management of cervical
      cancer.
AB  - The status of regional lymph nodes is the most important prognostic factor in
      early cervical cancer patients. Pelvic lymph node dissections are routinely
      performed as a part of standard surgical treatment. Systematic pelvic
      lymphadenectomy is associated with short- and long-term morbidities. This review
      discusses single components of the sentinel lymph node mapping (SLNM) technique
      and results of the detection of sentinel lymph nodes. SLNM biopsy performed by an
      experienced team for small volume tumors (<2 cm) has high specific side detection
      rate, excellent negative-predictive value and high sensitivity. Uncommon
      lymphatic drainage has been reported in 15% of cervical cancer patients. There is
      sufficient data now to suggest that SLNM with 99mTc plus blue dye in the hands of
      a surgeon with extensive experience should prove to be an important part of
      individualized cervical cancer surgery and increase the safety of less radical or
      fertility-sparing surgery. 

PMID- 23875665
TI  - Genetic changes in nonepithelial ovarian cancer.
AB  - Nonepithelial ovarian cancers (OCs), including sex cord-stromal tumors (SCSTs)
      and germ cell tumors (GCTs), are an uncommon subset of OC, together accounting
      for 10% of all OCs. The etiology of these tumors remains largely unresolved. It
      is well established that tumorigenesis is the result of multiple genetic
      alterations driving a normal cell toward a malignant state. Much effort has been
      made into researching the molecular mechanisms underlying epithelial OC, but far
      less is known about the genetic changes in SCSTs and GCTs. Recently, a single
      point missense mutation (C134W) was found in the FOXL2 gene in approximately 95%
      of adult-type granulosa cell tumors, suggesting a key role for FOXL2 in these
      tumors. By contrast, the FOXL2 mutation was not found in the juvenile type.
      DICER1 somatic missense mutations were found in approximately 60% of Sertoli
      Leydig tumors. Ovarian GCTs share many morphological features and a similar
      pattern of chromosomal alterations with testicular GCTs. In the latter, recent
      genome-wide association studies have identified seven susceptibility loci near
      KITLG, SPRY4, UKC2, BAK1, DMRT1, TERT and ATF7IP. All of the susceptibility loci
      detected thus far are all involved in primordial germ cell function or sex
      determination. TGF-beta/BMP and Wnt/beta-catenin signaling was absent in
      dysgerminomas, but present in yolk sac tumors, suggesting intertumoral
      heterogeneity. In this article, the authors aim to provide an overview of the
      current knowledge on the possible molecular changes in SCSTs and GCTs of the
      ovary. 

PMID- 23875666
TI  - The role of necroptosis, an alternative form of cell death, in cancer therapy.
AB  - Programmed cell death plays an important role in animal development, tissue
      homeostasis and eliminating harmful or virally infected cells. Necroptosis, a
      novel form of programmed cell death, is caspase independent but RIPK and RIPK3
      dependent. Moreover, it is suggested that necroptosis can be specifically
      inhibited by small molecular inhibitors such as necrostatin-1. Its signaling
      pathways have something in common with apoptosis, although the molecular
      mechanisms of necroptosis need to be further elucidated. Previous evidences
      suggest that necroptosis has significant effects in regulating various
      physiological processes and disease, such as ischemic brain injury, immune system
      disorders and cancer. In this review, the molecular mechanism of necroptosis is
      described and how it could be manipulated in the treatment of cancer is
      summarized. 

PMID- 23875667
TI  - Promoter-like sequences regulating transcriptional activity in neurexin and
      neuroligin genes.
AB  - Synapse function requires the cell-adhesion molecules neurexins (Nrxn) and
      neuroligins (Nlgn). Although these molecules are essential for neurotransmission
      and prefer distinct isoform combinations for interaction, little is known about
      their transcriptional regulation. Here, we started to explore this important
      aspect because expression of Nrxn1-3 and Nlgn1-3 genes is altered in mice lacking
      the transcriptional regulator methyl-CpG-binding protein2 (MeCP2). Since MeCP2
      can bind to methylated CpG-dinucleotides and Nrxn/Nlgn contain CpG-islands, we
      tested genomic sequences for transcriptional activity in reporter gene assays. We
      found that their influence on transcription are differentially activating or
      inhibiting. As we observed an activity difference between heterologous and
      neuronal cell lines for distinct Nrxn1 and Nlgn2 sequences, we dissected their
      putative promoter regions. In both genes, we identify regions in exon1 that can
      induce transcription, in addition to the alternative transcriptional start points
      in exon2. While the 5'-regions of Nrxn1 and Nlgn2 contain two CpG-rich elements
      that show distinct methylation frequency and binding to MeCP2, other regions may
      act independently of this transcriptional regulator. These data provide first
      insights into regulatory sequences of Nrxn and Nlgn genes that may represent an
      important aspect of their function at synapses in health and disease.

PMID- 23875668
TI  - Randomized comparison of vaginal self-sampling by standard vs. dry swabs for
      human papillomavirus testing.
AB  - BACKGROUND: To evaluate if human papillomavirus (HPV) self-sampling (Self-HPV)
      using a dry vaginal swab is a valid alternative for HPV testing. METHODS: Women
      attending colposcopy clinic were recruited to collect two consecutive Self-HPV
      samples: a Self-HPV using a dry swab (S-DRY) and a Self-HPV using a standard wet
      transport medium (S-WET). These samples were analyzed for HPV using real time PCR
      (Roche Cobas). Participants were randomized to determine the order of the tests.
      Questionnaires assessing preferences and acceptability for both tests were
      conducted. Subsequently, women were invited for colposcopic examination; a
      physician collected a cervical sample (physician-sampling) with a broom-type
      device and placed it into a liquid-based cytology medium. Specimens were then
      processed for the production of cytology slides and a Hybrid Capture HPV DNA test
      (Qiagen) was performed from the residual liquid. Biopsies were performed if
      indicated. Unweighted kappa statistics (k) and McNemar tests were used to measure
      the agreement among the sampling methods. RESULTS: A total of 120 women were
      randomized. Overall HPV prevalence was 68.7% (95% Confidence Interval (CI) 59.3
      77.2) by S-WET, 54.4% (95% CI 44.8-63.9) by S-DRY and 53.8% (95% CI 43.8-63.7) by
      HC. Among paired samples (S-WET and S-DRY), the overall agreement was good
      (85.7%; 95% CI 77.8-91.6) and the kappa was substantial (0.70; 95% CI 0.57-0.70).
      The proportion of positive type-specific HPV agreement was also good (77.3%; 95%
      CI 68.2-84.9). No differences in sensitivity for cervical intraepithelial
      neoplasia grade one (CIN1) or worse between the two Self-HPV tests were observed.
      Women reported the two Self-HPV tests as highly acceptable. CONCLUSION: Self-HPV
      using dry swab transfer does not appear to compromise specimen integrity. Further
      study in a large screening population is needed. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01316120.

PMID- 23875669
TI  - Processing factor for a selected group of pesticides in a wine-making process:
      distribution of pesticides during grape processing.
AB  - The processing factors (the pesticide concentration found in the wine/pesticide
      concentration found in grapes) of acetamiprid, azoxistrobin, carbaril,
      carbendazime, cyprodinil, dimethoate, dimethormorf, imazalil, imidacloprid,
      kresoxim methyl, penconazole, procymidone and thiabendazole were determined in a
      wine-making process. Pesticide analysis was performed using a multi-residue
      method for the determination of different pesticides both in wine and in grapes
      by extraction with acetonitrile followed by LC/MS. The pesticide distribution was
      studied for each step of the process, and the pesticide processing factors were
      calculated and found to vary among the different pesticides studied. pKow was
      found to affect a pesticide's processing factor; a linear correlation was
      obtained for all pesticide processing factors, except for dimethoate, which was
      the most water soluble. However, no correlation was found between the processing
      factor and the water solubility of pesticides. 

PMID- 23875670
TI  - Radiofrequency ablation at low irrigation flow rates using a novel 12-hole gold
      open-irrigation catheter.
AB  - BACKGROUND: High irrigation rates during radiofrequency (RF) ablation may cause
      fluid overload and limit lesion size. This in vivo animal study assessed the
      safety and efficacy of RF ablation at low irrigation rates using a novel 12-hole
      gold catheter. METHODS: A total of 103 lesions, created on the thigh of five
      mongrel dogs, were analyzed. Lesions were created using a 12-hole irrigated gold
      tip (Au) and a six-hole irrigated platinum-iridium (PtIr) catheter (both 7F/3.5
      mm electrode; BIOTRONIK SE & CO, KG, Berlin, Germany) in parallel and
      perpendicular orientation. RF current was delivered for 60 seconds at 30 W using
      8 mL/min and 15 mL/min irrigation. Electrode temperature, steam pops, lesion
      dimensions, and coagulum formation were recorded. RESULTS: Electrode temperatures
      were lower for Au compared to PtIr in parallel (8 mL/min: 38.1 +/- 1.7 degrees C
      vs 48.0 +/- 4.8 degrees C, P < 0.0001; 15 mL/min: 36.0 +/- 1.5 degrees C vs 46.9
      +/- 5.4 degrees C, P < 0.0001) and perpendicular position (15 mL/min: 35.5 +/-
      1.2 degrees C vs 38.4 +/- 2.5 degrees C, P = 0.003). The number of steam pops
      between Au and PtIr was comparable for parallel (8 mL/min: 14% vs 27%, P = 0.65;
      15 mL/min: 14% vs 43%, P = 0.21) and perpendicular orientation (8 mL/min: 25% vs
      17%, P = 1.00; 15 mL/min: 18% vs 0%, P = 0.48). Au created larger volumes than
      PtIr at 8 mL/min irrigation (861 +/- 251 mm(3) vs 504 +/- 212 mm(3) , P = 0.004);
      however, for 15 mL/min, volumes were comparable (624 +/- 269 mm(3) vs 768 +/- 466
      mm(3) , P = 0.46). No coagulum formation was observed for any of the catheters on
      the surface and catheter tip. CONCLUSION: RF ablation at low flow rate using a
      novel 12-hole irrigation Au catheter is safe and results in larger lesions than
      with a PtIr electrode.

PMID- 23875671
TI  - Single-molecule conductance of functionalized oligoynes: length dependence and
      junction evolution.
AB  - We report a combined experimental and theoretical investigation of the length
      dependence and anchor group dependence of the electrical conductance of a series
      of oligoyne molecular wires in single-molecule junctions with gold contacts.
      Experimentally, we focus on the synthesis and properties of diaryloligoynes with
      n = 1, 2, and 4 triple bonds and the anchor dihydrobenzo[b]thiophene (BT). For
      comparison, we also explored the aurophilic anchor group cyano (CN), amino (NH2),
      thiol (SH), and 4-pyridyl (PY). Scanning tunneling microscopy break junction (STM
      BJ) and mechanically controllable break junction (MCBJ) techniques are employed
      to investigate single-molecule conductance characteristics. The BT moiety is
      superior as compared to traditional anchoring groups investigated so far. BT
      terminated oligoynes display a 100% probability of junction formation and possess
      conductance values which are the highest of the oligoynes studied and, moreover,
      are higher than other conjugated molecular wires of similar length. Density
      functional theory (DFT)-based calculations are reported for oligoynes with n = 1
      4 triple bonds. Complete conductance traces and conductance distributions are
      computed for each family of molecules. The sliding of the anchor groups leads to
      oscillations in both the electrical conductance and the binding energies of the
      studied molecular wires. In agreement with experimental results, BT-terminated
      oligoynes are predicted to have a high electrical conductance. The experimental
      attenuation constants betaH range between 1.7 nm(-1) (CN) and 3.2 nm(-1) (SH) and
      show the following trend: betaH(CN) < betaH(NH2) < betaH(BT) < betaH(PY) ~
      betaH(SH). DFT-based calculations yield lower values, which range between 0.4 nm(
      1) (CN) and 2.2 nm(-1) (PY).

PMID- 23875673
TI  - Impaired endothelin calcium signaling coupled to endothelin type B receptors in
      penile arteries from insulin-resistant obese Zucker rats.
AB  - INTRODUCTION: Erectile dysfunction is considered as an early sign of subclinical
      vascular disease and endothelial dysfunction and a highly prevalent condition in
      diabetic patients. AIM: The current study assessed whether impaired vascular
      effects of endothelin (ET)-1 may contribute to the vascular dysfunction of penile
      arteries from a rat model of insulin resistance. METHODS: The effect of ETA and
      ETB receptor antagonists was assessed on the intracellular Ca(2+) [Ca(2+) ]i and
      contractile responses to ET-1 in penile arteries from obese Zucker rats (OZR) and
      lean Zucker rats (LZR), and ET receptor expression in the arterial wall was
      assessed by immunohistochemistry. MAIN OUTCOME MEASURE: Changes in ET-1 [Ca(2+)
      ]i and vasoconstriction and ET receptor expression were evaluated in penile
      arteries from insulin-resistant rats. RESULTS: ET-1-induced vasoconstriction was
      associated with a higher increase in smooth muscle [Ca(2+) ]i in penile arteries
      from OZR compared with LZR. Removal of the endothelium inhibited and enhanced
      contractions to the lowest and highest doses of ET-1, respectively, mainly in
      OZR. The selective ETA receptor antagonist BQ-123 inhibited ET-1 vasoconstriction
      and [Ca(2+) ]i response in both LZR and OZR. The ETB receptor antagonist BQ-788
      had little effect in healthy arteries but markedly inhibited ET-1-induced
      increases in [Ca(2+) ]i and vasoconstriction in arteries from OZR. ETA receptors
      were located on the smooth muscle and endothelium of penile arteries, whereas ETB
      receptors were found on the arterial endothelium in LZR and OZR, and also on the
      smooth muscle in OZR, immunostaining for both receptors being higher in OZR.
      CONCLUSION: Penile arteries from OZR exhibit an impaired ET-1 Ca(2+) signaling
      along with changes in the ET receptor profile. Thus, whereas ET-1 contraction and
      the associated [Ca(2+) ]i increase are mediated by smooth muscle ETA receptors in
      healthy arteries, ETB receptors contribute to contraction and are coupled to the
      augmented ET-1 [Ca(2+) ]i response under conditions of insulin resistance.

PMID- 23875674
TI  - A cross-sectional analysis of population demographics, HIV knowledge and risk
      behaviors, and prevalence and associations of HIV among men who have sex with men
      in the Gambia.
AB  - HIV epidemics in West Africa appear far more concentrated among key populations
      including men who have sex with men (MSM) and female sex workers (FSW) as
      compared to the more generalized epidemics of Southern and Eastern Africa. Since
      there has been no prior quantitative assessment of HIV risk among MSM in the
      Gambia, this study aims to describe the burden of HIV and associations of HIV
      infections. A total of 207 study participants reporting anal sex with another man
      in the previous 12 months were accrued using snowball sampling for this cross
      sectional study and were administered an anonymous structured questionnaire.
      Bivariate and multivariate logistic regression models were used to identify
      factors associated with prevalent HIV infections. HIV prevalence was 9.8%
      (20/205) and the highest HIV prevalence age group was among the participants who
      were older than 25 years with 22.9% (8/35) living with HIV. Less than 10% of
      participants reported always using condoms with male partners (19/201) while
      33.8% (69/204) of men reported no access to condoms and 82.5% (146/177) reported
      no access to latex condom-compatible lubricants (CCL). Knowledge of HIV risks was
      low with 3.5% (7/200) knowing that receptive anal intercourse was the highest
      risk sexual practice and CCL were the safest to use. This study highlighted that,
      similar to other West Africa countries, MSM are a high risk and underserved
      population for HIV prevention, treatment, and care services in the Gambia.
      Multilateral efforts including government, service providers, and community are
      needed to achieve reductions in HIV incidence and eventually prevalence among MSM
      in the Gambia.

PMID- 23875672
TI  - 3 Tesla multiparametric MRI for GTV-definition of Dominant Intraprostatic Lesions
      in patients with Prostate Cancer--an interobserver variability study.
AB  - PURPOSE: To evaluate the interobserver variability of gross tumor volume (GTV) -
      delineation of Dominant Intraprostatic Lesions (DIPL) in patients with prostate
      cancer using published MRI criteria for multiparametric MRI at 3 Tesla by 6
      different observers. MATERIAL AND METHODS: 90 GTV-datasets based on 15
      multiparametric MRI sequences (T2w, diffusion weighted (DWI) and dynamic contrast
      enhanced (DCE)) of 5 patients with prostate cancer were generated for GTV
      delineation of DIPL by 6 observers. The reference GTV-dataset was contoured by a
      radiologist with expertise in diagnostic imaging of prostate cancer using MRI.
      Subsequent GTV-delineation was performed by 5 radiation oncologists who received
      teaching of MRI-features of primary prostate cancer before starting contouring
      session. GTV-datasets were contoured using Oncentra Masterplan(r) and iplan(r)
      Net. For purposes of comparison GTV-datasets were imported to the Artiview(r)
      platform (Aquilab(r)), GTV-values and the similarity indices or Kappa indices
      (KI) were calculated with the postulation that a KI > 0.7 indicates excellent, a
      KI > 0.6 to < 0.7 substantial and KI > 0.5 to < 0.6 moderate agreement.
      Additionally all observers rated difficulties of contouring for each MRI-sequence
      using a 3 point rating scale (1 = easy to delineate, 2 = minor difficulties, 3 =
      major difficulties). RESULTS: GTV contouring using T2w (KI-T2w = 0.61) and DCE
      images (KI-DCE = 0.63) resulted in substantial agreement. GTV contouring using
      DWI images resulted in moderate agreement (KI-DWI = 0.51). KI-T2w and KI-DCE was
      significantly higher than KI-DWI (p = 0.01 and p = 0.003). Degree of difficulty
      in contouring GTV was significantly lower using T2w and DCE compared to DWI
      sequences (both p < 0.0001). Analysis of delineation differences revealed
      inadequate comparison of functional (DWI, DCE) to anatomical sequences (T2w) and
      lack of awareness of non-specific imaging findings as a source of erroneous
      delineation. CONCLUSIONS: Using T2w and DCE sequences at 3 Tesla for GTV
      definition of DIPL in prostate cancer patients by radiation oncologists with
      knowledge of MRI features results in substantial agreement compared to an
      experienced MRI-radiologist, but for radiotherapy purposes higher KI are
      desirable, strengthen the need for expert surveillance. DWI sequence for GTV
      delineation was considered as difficult in application.

PMID- 23875675
TI  - Concerted proton transfer mechanism of Clostridium thermocellum ribose-5
      phosphate isomerase.
AB  - Ribose-5-phosphate isomerase (Rpi) catalyzes the interconversion of D-ribose-5
      phosphate and D-ribulose-5-phosphate and plays an essential role in the pentose
      phosphate pathway and the Calvin cycle of photosynthesis. RpiB, one of the two
      isoforms of Rpi, is also a potential drug target for some pathogenic bacteria.
      Clostridium thermocellum ribose-5-phosphate isomerase (CtRpi), belonging to the
      RpiB family, has recently been employed in the industrial production of rare
      sugars because of its fast reaction kinetics and narrow substrate specificity. It
      is known that this enzyme adopts a proton transfer mechanism. It was suggested
      that the deprotonated Cys65 attracts the proton at C2 of the substrate to
      initiate the isomerization reaction, and this step is the rate-limiting step.
      However the elaborate catalytic mechanism is still unclear. We have performed
      quantum mechanical/molecular mechanical simulations of this rate-limiting step of
      the reaction catalyzed by CtRpi with the substrate D-ribose. Our results
      demonstrate that the deprotonated Cys65 is not a stable reactant. Instead, our
      calculations revealed a concerted proton-transfer mechanism: Asp8, a highly
      conserved residue in the RpiB family, performs as the base to abstract the proton
      at Cys65 and Cys65 in turn abstracting the proton of the D-ribose simultaneously.
      Moreover, we found Thr67 cannot catalyze the proton transfer from O2 to O1 of the
      D-ribose alone. Water molecule(s) may assist this proton transfer with Thr67. Our
      findings lead to a clear understanding of the catalysis mechanism of the RpiB
      family and should guide experiments to increase the catalysis efficiency. This
      study also highlights the importance of initial protonation states of cysteines.

PMID- 23875676
TI  - Deconstruction of stable cross-Beta fibrillar structures into toxic and nontoxic
      products using a mutated archaeal chaperonin.
AB  - Our group recently determined that a mutant archaeal chaperonin (Hsp 60)
      exhibited substantially enhanced protein folding activity at low temperatures and
      was able to deconstruct refractory protein aggregates. ATP dependent conversion
      of fibril structures into amorphous aggregates was observed in insulin amyloid
      preparations (Kurouski et al. Biochem. Biophys. Res. Commun. 2012). In the
      current study, mechanistic insights into insulin fibril deconstruction were
      obtained by examination of early stage complexes between Hsp60 and fibrils in the
      absence of ATP. Activity of the Hsp60 was significantly curtailed without ATP;
      however, some fibril deconstruction occurred, which is consistent with some
      models of the folding cycle that predict initial removal of unproductive protein
      folds. Chaperonin molecules adsorbed on the fibril surface and formed chaperonin
      clusters with no ATP present. We propose that there are specific locations on the
      fibril surface where chaperonin can unravel the fibril to release short
      fragments. Spontaneous coagulation of these fibril fragments resulted in the
      formation of amorphous aggregates without the release of insulin into solution.
      The addition of ATP significantly increased the toxicity of the insulin fibril
      chaperonin reaction products toward mammalian cells. 

PMID- 23875677
TI  - Role of osteopontin in differential diagnosis of ovarian tumors.
AB  - AIM: The aim of this study was to evaluate the role of the serum osteopontin
      (OPN) level as a biomarker for discriminating between malignant and benign
      ovarian tumors. Furthermore, comparisons with the diagnostic usefulness of the
      other tests were performed. METHODS: The study included 114 consecutive women
      with ovarian tumors (82 benign and 32 malignant) who were referred to our
      division. RESULTS: A cut-off level of 28.0 ng/mL for OPN showed a sensitivity of
      71.87% and a specificity of 89.02%. The area under the receiver-operator curve
      (ROC) was 0.812. There were no differences in diagnostic utility between OPN and
      the other studied tests. OPN levels were lower in patients with endometriotic
      ovarian cysts than in those with other benign ovarian tumors (14.00 vs 19.50
      ng/mL; P = 0.018). The difference between the median OPN level in patients with
      endometriotic cysts (14.0 ng/mL) and those with malignant tumors (40.85 ng/mL)
      was also statistically significant (P < 0.0001). The calculated OPN/CA-125 ratio
      was significantly different between patients with endometriotic cysts (median,
      0.36; range, 0.05-2.89) and those with other benign tumors (median, 1.25; range,
      0.05-5.70) (P = 0.0002). There was also a statistically significant difference in
      the median OPN/CA-125 ratio between patients with endometrial cysts (median,
      0.36; range, 0.05-2.89) and those with malignant tumors (median, 0.12; range,
      0.01-3.39) (P = 0.004). CONCLUSION: The diagnostic utility of OPN is similar to
      that of ultrasonographic evaluation and CA-125 level assessment. Thus, OPN may be
      useful in differential diagnosis for less experienced ultrasonographers and is
      especially valuable for differential diagnosis of endometriotic cysts.

PMID- 23875678
TI  - Natural and pyrogenic humic acids at goethite and natural oxide surfaces
      interacting with phosphate.
AB  - Fulvic and humic acids have a large variability in binding to metal (hydr) oxide
      surfaces and interact differently with oxyanions, as examined here
      experimentally. Pyrogenic humic acid has been included in our study since it will
      be released to the environment in the case of large-scale application of biochar,
      potentially creating Darks Earths or Terra Preta soils. A surface complexation
      approach has been developed that aims to describe the competitive behavior of
      natural organic matter (NOM) in soil as well as model systems. Modeling points
      unexpectedly to a strong change of the molecular conformation of humic acid (HA)
      with a predominant adsorption in the Stern layer domain at low NOM loading. In
      soil, mineral oxide surfaces remain efficiently loaded by mineral-protected
      organic carbon (OC), equivalent with a layer thickness of >= ~0.5 nm that
      represents at least 0.1-1.0% OC, while surface-associated OC may be even three
      times higher. In natural systems, surface complexation modeling should account
      for this pervasive NOM coverage. With our charge distribution model for NOM (NOM
      CD), the pH-dependent oxyanion competition of the organo-mineral oxide fraction
      can be described. For pyrogenic HA, a more than 10-fold increase in dissolved
      phosphate is predicted at long-term applications of biochar or black carbon.

PMID- 23875679
TI  - Online sequential-injection chromatography with stepwise gradient elution: a tool
      for studying the simultaneous adsorption of herbicides on soil and soil
      components.
AB  - The adsorption of triazine herbicides simazine (SIM), atrazine (ATR), and
      propazine (PRO) as well as the metabolites deisopropylatrazine (DIA),
      deethylatrazine (DEA), and 2-hydroxyatrazine (HAT) on soil, humic acid, and soil
      modified with humic acidic was studied by sequential-injection chromatography
      with UV detection at 223 nm. An online monitoring system was assembled, which was
      composed of a tangential filter and a peristaltic pump for the circulation of the
      soil (25 g L(-1)) or humic acid (2.5 g L(-1)) suspensions. A stepwise gradient
      elution separated the compounds using three mobile phases whose compositions were
      28, 40, and 50% (v v(-1)) methanol in 1.25 mmol L(-1) ammonium acetate buffer, pH
      4.7. The sampling throughput was about six analyses per hour; the linear dynamic
      range was between 100 and 1000 MUg L(-1) for all of the studied compounds. The
      detection limits varied from 9 MUg L(-1) for ATR to 36 MUg L(-1) for DEA. At
      contact times <2 h, humic acid was the material with a higher adsorptive capacity
      (from 1470 +/- 43 MUg g(-1) for DIA to 2380 +/- 51 MUg g(-1) for PRO). In soil,
      HAT exhibited the highest adsorption (23.8 +/- 0.2 MUg g(-1)). The presence of
      humic acid in the soil increased the adsorption of ATR (14 +/- 1 to 23 +/- 2 MUg
      g(-1)) and PRO (21.5 +/- 0.5 to 24.0 +/- 0.2 MUg g(-1)), decreased the adsorption
      of HAT (23.8 +/- 0.2 to 18 +/- 2 MUg g(-1)), and did not affect DIA and DEA. The
      adsorption of SIM was negligible in all of the sorbents studied. Simazine is the
      herbicide with the greatest potential for leaching to water bodies followed by
      DEA and DIA. 

PMID- 23875680
TI  - Lacrimal sac empyema incision and drainage followed by early external
      dacryocystorhinostomy.
AB  - PURPOSE: To evaluate the success of lacrimal sac empyema incision and drainage
      followed by early external dacryocystorhinostomy. METHODS: Interventional
      consecutive case series conducted in Farabi Eye Hospital between August 2007 and
      November 2010. Patients with acute dacyocystitis and lacrimal sac empyema
      underwent incision and drainage, followed by early (less than 4 weeks) external
      DCR. Data collection included patient demographics, past medical history,
      procedure technique, culture results, and formation of a persistent cutaneous
      fistula. RESULTS: A total of 32 patients were included: 87.5% had a positive
      history of chronic epiphora before dacryocystitis. Of these 32 cases, 55.6% had
      positive culture. Staphylococcus aureus was the most common organism with 8
      isolates (38%). The average number of days between empyema drainage and DCR was
      11.44 days. All patients had complete resolution of dacryocystitis, with no
      recurrence during the follow-up period. Neither of 32 patients treated with early
      DCR after primary empyema drainage, developed a persistent lacrimal-cutaneous
      fistula. CONCLUSIONS: Incision and drainage of the lacrimal sac empyema followed
      by early external dacryocystorhinostomy can be an appropriate treatment strategy
      for acute dacryocystitis.

PMID- 23875681
TI  - Biological impact assessment of nanomaterial used in nanomedicine. introduction
      to the NanoTEST project.
AB  - Therapeutic nanoparticles (NPs) are used in nanomedicine as drug carriers or
      imaging agents, providing increased selectivity/specificity for diseased tissues.
      The first NPs in nanomedicine were developed for increasing the efficacy of known
      drugs displaying dose-limiting toxicity and poor bioavailability and for
      enhancing disease detection. Nanotechnologies have gained much interest owing to
      their huge potential for applications in industry and medicine. It is necessary
      to ensure and control the biocompatibility of the components of therapeutic NPs
      to guarantee that intrinsic toxicity does not overtake the benefits. In addition
      to monitoring their toxicity in vitro, in vivo and in silico, it is also
      necessary to understand their distribution in the human body, their
      biodegradation and excretion routes and dispersion in the environment. Therefore,
      a deep understanding of their interactions with living tissues and of their
      possible effects in the human (and animal) body is required for the safe use of
      nanoparticulate formulations. Obtaining this information was the main aim of the
      NanoTEST project, and the goals of the reports collected together in this special
      issue are to summarise the observations and results obtained by the participating
      research teams and to provide methodological tools for evaluating the biological
      impact of NPs.

PMID- 23875682
TI  - Total synthesis of the proposed structure of didemnaketal B.
AB  - Total synthesis of the proposed structure of didemnaketal B has been
      accomplished. The C7-C21 spiroacetal domain was synthesized by exploiting our
      Suzuki-Miyaura coupling/spiroacetalization strategy. The C1-C7 acyclic domain was
      constructed via an Evans syn-aldol reaction and a vinylogous Mukaiyama aldol
      reaction. Finally, the C22-C28 side chain was introduced by means of a Nozaki
      Hiyama-Kishi reaction. Comparison of the NMR spectroscopic data of our synthetic
      material with those of the authentic sample revealed that the proposed structure
      requires stereochemical reassignment. 

PMID- 23875683
TI  - Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE.
AB  - BACKGROUND: Funded by the National Institutes of Health (NIH), the aim of the
      Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the
      biological research community with a comprehensive encyclopedia of functional
      genomic elements for both model organisms C. elegans (worm) and D. melanogaster
      (fly). With a total size of just under 10 terabytes of data collected and
      released to the public, one of the challenges faced by researchers is to extract
      biologically meaningful knowledge from this large data set. While the basic
      quality control, pre-processing, and analysis of the data has already been
      performed by members of the modENCODE consortium, many researchers will wish to
      reinterpret the data set using modifications and enhancements of the original
      protocols, or combine modENCODE data with other data sets. Unfortunately this can
      be a time consuming and logistically challenging proposition. RESULTS: In
      recognition of this challenge, the modENCODE DCC has released uniform computing
      resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE
      DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the
      private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In
      particular, we have released Galaxy workflows for interpreting ChIP-seq data
      which use the same quality control (QC) and peak calling standards adopted by the
      modENCODE and ENCODE communities. For convenience of use, we have created Amazon
      and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE
      data, software and other dependencies. CONCLUSIONS: Using these resources
      provides a framework for running consistent and reproducible analyses on
      modENCODE data, ultimately allowing researchers to use more of their time using
      modENCODE data, and less time moving it around.

PMID- 23875684
TI  - Millennium development health metrics: where do Africa's children and women of
      childbearing age live?
AB  - The Millennium Development Goals (MDGs) have prompted an expansion in approaches
      to deriving health metrics to measure progress toward their achievement. Accurate
      measurements should take into account the high degrees of spatial heterogeneity
      in health risks across countries, and this has prompted the development of
      sophisticated cartographic techniques for mapping and modeling risks. Conversion
      of these risks to relevant population-based metrics requires equally detailed
      information on the spatial distribution and attributes of the denominator
      populations. However, spatial information on age and sex composition over large
      areas is lacking, prompting many influential studies that have rigorously
      accounted for health risk heterogeneities to overlook the substantial demographic
      variations that exist subnationally and merely apply national-level
      adjustments.Here we outline the development of high resolution age- and sex
      structured spatial population datasets for Africa in 2000-2015 built from over a
      million measurements from more than 20,000 subnational units, increasing input
      data detail from previous studies by over 400-fold. We analyze the large spatial
      variations seen within countries and across the continent for key MDG indicator
      groups, focusing on children under 5 and women of childbearing age, and find that
      substantial differences in health and development indicators can result through
      using only national level statistics, compared to accounting for subnational
      variation.Progress toward meeting the MDGs will be measured through national
      level indicators that mask substantial inequalities and heterogeneities across
      nations. Cartographic approaches are providing opportunities for quantitative
      assessments of these inequalities and the targeting of interventions, but
      demographic spatial datasets to support such efforts remain reliant on coarse and
      outdated input data for accurately locating risk groups. We have shown here that
      sufficient data exist to map the distribution of key vulnerable groups, and that
      doing so has substantial impacts on derived metrics through accounting for
      spatial demographic heterogeneities that exist within nations across Africa. 

PMID- 23875686
TI  - Are Chileans exposed to dietary furan?
AB  - Chilean consumer preferences include foods that may contain considerable amounts
      of furan, a potential human carcinogen. However, there is no information
      regarding dietary exposure to furan in Chile. Thus, the objective of this work
      was to determine the Chilean exposure to dietary furan. To accomplish this
      objective, the furan concentration of 14 types of commercial foods processed at
      high temperature were analysed based on a modified headspace-GC/MS (HS-GC/MS)
      method in which the limits of detection for different food matrices ranged from
      0.01 to 0.6 ng g(-1). In addition, a risk assessment was made with exposure
      estimates based on dietary data from national studies on different age groups (9
      month-old babies, school children, adults and elderly people). Of the food items
      surveyed "American"-type coffee (espresso coffee plus hot water) obtained from
      automatic coffee machine (936 ng g(-1)) and low moisture starchy products like
      crisps and "soda"-type crackers showed the highest furan concentrations (259 and
      91 ng g(-1), respectively). Furthermore, furan was also found in samples of
      breakfast cereals (approximately 20 ng g(-1)), jarred fruit baby foods (8.5 ng g(
      1)) and orange juice (7.0 ng g(-1)). School children (aged 9-13 years)
      represented the highest intake of furan (about 500 ng kg(-1)(bw) day(-1)), with
      margins of exposure of 2479 and 2411, respectively, which points to a possible
      public health risk.

PMID- 23875687
TI  - Long non-coding RNAs and their implications in cancer epigenetics.
AB  - LncRNAs (long non-coding RNAs) have emerged as key molecular players in the
      regulation of gene expression in different biological processes. Their
      involvement in epigenetic processes includes the recruitment of histone-modifying
      enzymes and DNA methyltransferases, leading to the establishment of chromatin
      conformation patterns that ultimately result in the fine control of genes. Some
      of these genes are related to tumorigenesis and it is well documented that the
      misregulation of epigenetic marks leads to cancer. In this review, we highlight
      how some of the lncRNAs implicated in cancer are involved in the epigenetic
      control of gene expression. While very few lncRNAs have already been identified
      as players in determining the cancer-survival outcome in a number of different
      cancer types, for most of the lncRNAs associated with epigenetic regulation only
      their altered pattern of expression in cancer is demonstrated. Thanks to their
      tissue-specificity features, lncRNAs have already been proposed as diagnostic
      markers in specific cancer types. We envision the discovery of a wealth of novel
      spliced and unspliced intronic lncRNAs involved in epigenetic networks or in
      highly location-specific epigenetic control, which might be predominantly altered
      in specific cancer subtypes. We expect that the characterization of new lncRNA
      (long non-coding RNA)-protein and lncRNA-DNA interactions will contribute to the
      discovery of potential lncRNA targets for use in therapies against cancer. 

PMID- 23875688
TI  - Simulating the mechanism of antimicrobial lipopeptides with all-atom molecular
      dynamics.
AB  - The emergence of antibiotic resistant pathogens is one of the major medical
      concerns of the 21st century, prompting renewed interest in the development of
      novel antimicrobial compounds. Here we use microsecond-scale all-atom molecular
      dynamics simulations to characterize the structure, dynamics, and membrane
      binding mechanism of a synthetic antimicrobial lipopeptide, C16-KGGK. Our
      simulations suggest that these lipopeptides prefer to aggregate in solution and
      alter the intrinsic order of the lipid bilayer upon binding. From these results
      and previous coarse-grained simulations, we have developed a simple model for the
      binding and insertion process for these lipopeptides. 

PMID- 23875689
TI  - Colorectal cancer-susceptibility single-nucleotide polymorphisms in Korean
      population.
AB  - BACKGROUND AND AIM: Considering the significant racial and ethnic diversity in
      genetic variation, it is unclear whether the genome-wide association studies
      identified colorectal cancer (CRC)-susceptibility single-nucleotide polymorphisms
      (SNPs) discovered in European populations are also relevant to the Korean
      population. However, studies on CRC-susceptibility SNPs in Koreans are limited.
      METHODS: To investigate the racial and ethnic diversity of CRC-susceptibility
      genetic variants, we genotyped for the established European CRC-susceptibility
      SNPs in 198 CRC cases and 329 controls in Korea. To identify novel genetic
      variants using genome-wide screening in Korea, Illumina HumanHap 370K/610K
      BeadChips were performed on 105 CRC patients, and candidate CRC-susceptibility
      SNPs were selected. Subsequently, genotyping for replication was done in 189 CRC
      cases and 190 controls. RESULTS: Among the European CRC-susceptibility SNPs,
      rs4939827 in SMAD7 was associated with a significant decreased risk of Korean CRC
      (age-/gender-adjusted odds ratio [95% confidence interval]: additive model, 0.67
      [95% CI, 0.47-0.95]; dominant model, 0.59 [95% CI, 0.39-0.91]). rs4779584 and
      rs10795668 were associated with CRC risk in females and males, respectively.
      Among candidate CRC-susceptibility SNPs selected from genome-wide screening,
      novel SNP, rs17051076, was found to be associated with a significantly increased
      risk of microsatellite instability-high CRC (age-/gender-adjusted odds ratio [95%
      confidence interval]: additive model, 4.25 [95% CI, 1.51-11.98]; dominant model,
      3.52 [95% CI, 1.13-10.94]) in the replication study. CONCLUSIONS: rs4939827,
      rs4779584, and rs10795668 may contribute to the risk of CRC in the Korean
      population as well as in European populations. Novel rs17051076 could be
      associated with microsatellite instability-high CRC in Koreans. These
      associations support the ethnic diversity of CRC-susceptibility SNPs and should
      be taken into account in large-scale studies.

PMID- 23875690
TI  - Boronic esters in asymmetric synthesis.
AB  - The author's work on (alpha-haloalkyl)boronic esters as reagents for asymmetric
      synthesis is reviewed. Diastereomeric ratios exceeding 1000 can be achieved with
      this chemistry, and ratios around 100 are commonplace. The method allows
      sequential installation of a series of stereocenters and tolerates a wide variety
      of suitably protected functional substituents. (alpha-Amidoalkyl)boronic acids
      include biochemically significant serine protease inhibitors, one of which is the
      clinically successful proteasome inhibitor bortezomib, used for treatment of
      multiple myeloma and mantle cell lymphoma. 

PMID- 23875691
TI  - Evaluation of the currency of the Davies and Oberle (1990) model of supportive
      care in specialist and specialised palliative care settings in England.
AB  - AIMS AND OBJECTIVES: To evaluate the extent to which the Davies and Oberle (1990)
      model of supportive nursing has currency across specialist and specialised care
      settings in England. BACKGROUND: The model describes attributes of palliative
      nursing for practice and associated educational curricula. It is influential but
      predates introduction of specialist/specialised care. Its applicability in
      contemporary care settings has not been evaluated. DESIGN: Evaluation was
      undertaken using sequential mixed methods, predominantly qualitative. Data
      collected during 2008-2009. METHODS: Four stages: (1) focus groups involving
      hospital and community palliative clinical nurse specialists and nurses from
      three hospice settings (total = 25) to identify setting-specific characteristics,
      (2) survey of nurses (n = 48 respondents/31%) with follow-up interviews (n = 25)
      to identify congruence with the model, (3) interviews with patients (n = 6) and
      carers (n = 13) for practice evidence and (4) reconvened focus groups (n = 19
      nurses) for confirmation. RESULTS: All major dimensions were evidenced.
      'Connecting' had reduced emphasis in the hospital setting where specialist nurses
      spend limited time with patients, but diminishing time to 'connect' with patients
      and carers as service develops could potentially become problematic across all
      settings. Two new dimensions ('Displaying expertise' and 'Influencing other
      professionals') with subdimensions (e.g. 'Advanced communication skills') are
      proposed as additions to reflect advanced practice. Further new subdimensions
      ('Making the assessment', 'Prioritising', 'Agreeing the plan') are suggested to
      be best aligned with the existing dimension 'Connecting'. CONCLUSIONS: A revised
      model of supportive care incorporating dimensions of advanced nursing has
      currency in contemporary specialist/specialised care settings, although
      evaluation is required as to the actual impact of the model on care outcomes.
      'Connecting' is currently being affected by pace of work and lateness of
      referrals. IMPLICATIONS FOR PRACTICE: 'Spending time' is increasingly difficult
      to sustain so challenging nurses as to how they may continue to 'connect' with
      patients as service delivery continues to change.

PMID- 23875692
TI  - Structure of polydopamine: a never-ending story?
AB  - Polydopamine (PDA) formed by the oxidation of dopamine is an important polymer,
      in particular, for coating various surfaces. It is composed of dihydroxyindole,
      indoledione, and dopamine units, which are assumed to be covalently linked.
      Although PDA has been applied in a manifold way, its structure is still under
      discussion. Similarities have been observed in melanins/eumelanins as naturally
      occurring, deeply colored polymer pigments derived from L-DOPA. Recently, an
      alternative structure was proposed for PDA wherein dihydroxyindoline,
      indolinedione, and eventually dopamine units are not covalently linked to each
      other but are held together by hydrogen bonding between oxygen atoms or pi
      stacking. In this study, we show that this structural proposal is very unlikely
      to occur taking into account unambiguous results obtained by different analytical
      methods, among them (13)C CPPI MAS NMR (cross-polarization polarization-inversion
      magic angle spinning NMR), (1)H MAS NMR (magic angle spinning NMR), and ES-HRMS
      (electrospray ionization high-resolution mass spectrometry) for the first time in
      addition to XPS (X-ray photoelectron spectroscopy) and FTIR spectroscopy. The
      results give rise to a verified structural assignment of PDA wherein
      dihydroxyindole and indoledione units with different degrees of (un)saturation
      are covalently linked by C-C bonds between their benzene rings. Furthermore,
      proof of open-chain (dopamine) monomer units in PDA is provided. Advanced DFT
      calculations imply the arrangements of several PDA chains preferably by quinone
      hydroquinone-type interactions in a parallel or antiparallel manner. From all of
      these results, a number of hypotheses published before could be experimentally
      supported or were found to be contradictory, thus leading to a better
      understanding of the PDA structure.

PMID- 23875693
TI  - Effect of ion pairing on the solution dynamics investigated by the simulations of
      the optical Kerr effect and the dielectric relaxation spectra.
AB  - The optical Kerr effect (OKE) and dielectric relaxation spectroscopy (DRS)
      signals of MgCl2 aqueous solutions were modeled based on the same group of
      molecular dynamics simulation trajectories. Plausible agreement between the
      simulations and the experiments allows us to analyze the microscopic origin of
      the different concentration dependences of relaxation times probed by these two
      techniques. Our simulations suggest that a significant amount of cations and
      anions associate in the solutions due to the ion pairing effect. These ion
      assemblies as well as the free cations form suspending clusters together with the
      water molecules in their cation hydration shells. The dynamics of water molecules
      in these clusters is significantly hindered, while that of other water molecules
      remains largely unaffected. The relaxation times measured by OKE and DRS have
      different concentration dependences because DRS probes only the rotational
      dynamics of water molecules outside of the cluster while OKE contains the
      information of dynamics of all of the water molecules in the solutions. Such
      findings provide us a microscopic picture on how the ion hydration affects the
      water dynamics in certain ionic solutions in which ion pairing plays an important
      role. 

PMID- 23875694
TI  - Control of heterogeneous Fe(III) (hydr)oxide nucleation and growth by interfacial
      energies and local saturations.
AB  - To predict the fate of aqueous pollutants, a better understanding of
      heterogeneous Fe(III) (hydr)oxide nucleation and growth on abundant mineral
      surfaces is needed. In this study, we measured in situ heterogeneous Fe(III)
      (hydr)oxide nucleation and growth on quartz, muscovite, and corundum (Al2O3) in
      10(-4) M Fe(III) solution (in 10 mM NaNO3 at pH = 3.7 +/- 0.2) using grazing
      incidence small-angle X-ray scattering (GISAXS). Interestingly, both the fastest
      heterogeneous nucleation and slowest growth occurred on corundum. To elucidate
      the mechanisms, zeta potential and water contact angle measurements were
      conducted. Electrostatic forces between the charged Fe(III) (hydr)oxide polymeric
      embryos and substrate surfaces-which affect local saturations near the substrate
      surfaces-controlled heterogeneous growth rates. Water contact angles (7.5 degrees
      +/- 0.7, 22.8 degrees  +/- 1.7, and 44.8 degrees  +/- 3.7 for quartz, muscovite,
      and corundum, respectively) indicate that corundum has the highest substrate
      water interfacial energy. Furthermore, a comparison of structural mismatches
      between the substrates and precipitates indicates a lowest precipitate-substrate
      interfacial energy for corundum. The fastest nucleation on corundum suggests that
      interfacial energies in the solution-substrate-precipitate system controlled
      heterogeneous nucleation rates. The unique information provided here bolsters our
      understanding of nanoparticle-mineral surface interactions, mineral surface
      modification by iron oxide coating, and pollutant transport. 

PMID- 23875695
TI  - Current pattern of Ponderal Indices of term small-for-gestational age in a
      population of Nigerian babies.
AB  - BACKGROUND: Small-for-gestational age (SGA) newborns constitute a special group
      of neonates who may have suffered varying degrees of intrauterine insults and
      deprivation. Variations in birth weight, length and Ponderal Index (PI) depend on
      the type and degree of intrauterine insults the babies were exposed to. The
      objective of the study was to determine the current prevalence of term SGA births
      in a Nigerian Tertiary Hospital and the current pattern of Ponderal Indices among
      term SGA in a population of Nigerian babies. METHODS: Subjects comprised of
      consecutive term singleton mother-baby pairs in the first 24 hours of life. It
      was a cross sectional study. The anthropometric parameters of each baby were
      recorded and the PI was also determined. RESULTS: Out of 1,052 live births during
      the study period (September to December, 2009), 825 were term, singleton babies.
      Five hundred and eight-one babies (70.4%) fall into the upper socio-economic
      classes 1 and II, 193 (23.4%) in the middle class and 51 (6.2%) were of the lower
      classes IV and V. None of the mothers indicated ingestion of alcohol or smoking
      of cigarette. Fifty-nine babies (7.2%) were small-for gestational age (SGA). Of
      the 59 SGA subjects, 26 (44.1%) were symmetrical SGA while 33 (55.9%) were
      asymmetrical SGA. There was no significant sex or socioeconomic predilection for
      either symmetrical or asymmetrical growth (p = 0.59, 0.73 respectively).
      CONCLUSION: The findings showed that proportionality in SGA fetuses is a
      continuum, with the PI depending on the duration of intrauterine insult and the
      extent of its effects on weight and length before delivery.

PMID- 23875696
TI  - Novel gamma-secretase modulators for the treatment of Alzheimer's disease: a
      review focusing on patents from 2010 to 2012.
AB  - INTRODUCTION: gamma-Secretase is the enzyme responsible for the final step of
      amyloid precursor protein proteolysis to generate Abeta peptides including
      Abeta42 which is believed to be a toxic species involved in Alzheimer's disease
      (AD) progression. gamma-Secretase modulators (GSMs) have been shown to
      selectively lower Abeta42 production without affecting total Abeta levels or the
      formation of gamma-secretase substrate intracellular domains such as APP
      intracellular domain and Notch intracellular domain. Therefore, GSMs have emerged
      as an important therapeutic strategy for the treatment of AD. AREAS COVERED: The
      literature covering novel GSMs will be reviewed focusing on patents from 2010 to
      2012. EXPERT OPINION: During the last review period (2008 - 2010) considerable
      progress was made developing GSMs with improved potency for lowering Abeta42
      levels, but most of the compounds resided in unfavorable central nervous system
      (CNS) drug space. In this review period (2010 - 2012), there is a higher
      percentage of potent GSM chemical matter that resides in favorable CNS drug
      space. It is anticipated that clinical candidates will emerge out of this cohort
      that will be able to test the GSM mechanism of action in the clinic.

PMID- 23875697
TI  - Potential of the SPY intraoperative perfusion assessment system to reduce
      ischemic complications in immediate postmastectomy breast reconstruction.
AB  - BACKGROUND: The quality and viability of mastectomy flaps remain a central
      challenge in reconstructive surgery, particularly for immediate breast
      reconstruction. Insufficient perfusion in tissue flaps is a leading cause of
      early complications following reconstructive procedures, and clinical judgment
      alone is not completely reliable for the assessment of flap viability. Accurate
      and reliable intraoperative methods for assessment of tissue perfusion are needed
      to help surgeons identify tissue at risk for ischemia and necrosis, thereby
      allowing for maneuvers to improve tissue flap viability. METHODS: This study
      evaluates the use of intraoperative laser angiography using the SPY System
      (LifeCell Corp., Branchburg, NJ) for the assessment of perfusion in mastectomy
      flaps for immediate breast reconstruction. The SPY System uses the contrast agent
      indocyanine green, which has an excellent safety profile and pharmacokinetics
      that allow for repeat evaluations during the same surgical procedure. In recent
      work, the SPY System has demonstrated high sensitivity and specificity for
      detection of tissues at risk for ischemia and necrosis during reconstructive
      surgery. Using a retrospective, chart-review design, the authors compared
      consecutive cases of immediate breast reconstruction using a prosthesis, before
      and after implementation of the SPY System. RESULTS: Ninety-one subjects were
      included in the analysis: 52 prior to SPY (Pre-SPY) and 39 after implementation
      of SPY (Post-SPY). Baseline characteristics were similar between the groups. Both
      groups had high rates of comorbidities, chemotherapy, and radiation therapy. The
      rate of postoperative complications was two-fold higher in the Pre-SPY group
      compared to the Post-SPY group (36.5% vs. 17.9%); this difference was of
      borderline significance (P = 0.0631). However, mean number of repeat visits to
      the OR per patient was significantly higher in the Pre-SPY group (1.21 +/- 1.47
      vs. 0.41 +/- 0.71; P = 0.0023). Of the seven patients with complications in the
      Post-SPY group, five were identified by SPY as having poor flap perfusion; none
      were identified by clinical judgment alone. CONCLUSIONS: This study suggests that
      the SPY System can contribute to reduced ischemia-related complications in a
      population of women undergoing immediate breast reconstruction following
      mastectomy for breast cancer.

PMID- 23875698
TI  - Secondary provoked vestibulodynia in sexually active women with uncomplicated
      recurrent urinary tract infections.
AB  - INTRODUCTION: Uncomplicated recurrent urinary tract infections (rUTIs) associated
      with uropathogenic Escherichia coli (UPEC) are common among healthy, reproductive
      aged women. Provoked vestibulodynia (PVD) is a major reason of sexual pain in
      premenopausal women. AIM: The aim of this paper is to assess prevalence and
      predictors of secondary PVD in a cohort of Caucasian-European, heterosexual,
      sexually active, reproductive-aged women seeking medical help for rUTIs as their
      primary complaint. METHODS: Clinical and psychometric variables for 60
      consecutive patients with rUTIs were considered. Patients were assessed with a
      thorough medical and sexual history, a number of psychometric instruments, and a
      specific physical examination. Urinalysis and self-collected urine cultures from
      the previous 12 months were also examined. MAIN OUTCOME MEASURE: Descriptive
      statistics and logistic regression models were used to test the associations
      between secondary PVD and sociodemographic and clinical variables. RESULTS: Mean
      age was 34.2 years (median 33 years; range 21-42). Secondary PVD was found in 36
      of 60 patients (60%). Women with PVD had a higher prevalence of urinary tract
      infections (UTIs) over the previous 12 months (chi(2) : 4.54; P = 0.03) and
      suffered more frequently from UPEC-related rUTIs (chi(2) : 5.92; P = 0.01) than
      those without PVD. Moreover, women with PVD showed significantly lower scores on
      Female Sexual Function Index domains (all P <= 0.01), as compared with PVD
      negative women. UPEC-related rUTIs (odds ratio [OR]: 3.1; P = 0.01), six or more
      UTIs over the previous 12 months (OR: 2.8; P = 0.01), and treatment with three or
      more antibiotics throughout the same period (OR: 2.1; P = 0.04) emerged as
      independent predictors of PVD. CONCLUSIONS: Three of five Caucasian-European,
      heterosexual, sexually active women of reproductive age complaining of rUTIs as
      their primary disorder also suffer from secondary PVD. Uncomplicated UPEC-related
      rUTIs are more frequently associated with secondary PVD than are UTIs caused by
      different uropathogens.

PMID- 23875699
TI  - Solid-state NMR approaches to internal dynamics of proteins: from picoseconds to
      microseconds and seconds.
AB  - Solid-state nuclear magnetic resonance (NMR) spectroscopy has matured to the
      point that it is possible to determine the structure of proteins in immobilized
      states, such as within microcrystals or embedded in membranes. Currently,
      researchers continue to develop and apply NMR techniques that can deliver site
      resolved dynamic information toward the goal of understanding protein function at
      the atomic scale. As a widely-used, natural approach, researchers have mostly
      measured longitudinal (T1) relaxation times, which, like in solution-state NMR,
      are sensitive to picosecond and nanosecond motions, and motionally averaged
      dipolar couplings, which provide an integral amplitude of all motions with a
      correlation time of up to a few microseconds. While overall Brownian tumbling in
      solution mostly precludes access to slower internal dynamics, dedicated solid
      state NMR approaches are now emerging as powerful new options. In this Account,
      we give an overview of the classes of solid-state NMR experiments that have
      expanded the accessible range correlation times from microseconds to many
      milliseconds. The measurement of relaxation times in the rotating frame, T1rho,
      now allows researchers to access the microsecond range. Using our recent
      theoretical work, researchers can now quantitatively analyze this data to
      distinguish relaxation due to chemical-shift anisotropy (CSA) from that due to
      dipole-dipole couplings. Off-resonance irradiation allows researchers to extend
      the frequency range of such experiments. We have built multidimensional analogues
      of T2-type or line shape experiments using variants of the dipolar-chemical shift
      correlation (DIPSHIFT) experiment that are particularly suited to extract
      intermediate time scale motions in the millisecond range. In addition, we have
      continuously improved variants of exchange experiments, mostly relying on the
      recoupling of anisotropic interactions to address ultraslow motions in the ms to
      s ranges. The NH dipolar coupling offers a useful probe of local dynamics,
      especially with proton-depleted samples that suppress the adverse effect of
      strong proton dipolar couplings. We demonstrate how these techniques have
      provided a concise picture of the internal dynamics in a popular model system,
      the SH3 domain of alpha-spectrin. T1-based methods have shown that large
      amplitude bond orientation fluctuations in the picosecond range and slower 10 ns
      low-amplitude motions coexist in these structures. When we include T1rho data, we
      observe that many residues undergo low amplitude motions slower than 100 ns. On
      the millisecond to second scale, mostly localized but potentially cooperative
      motions occur. Comparing different exchange experiments, we found that terminal
      NH2 groups in side chains can even undergo a combination of ultraslow large-angle
      two-site jumps accompanied by small-angle fluctuations that occur 10 times more
      quickly. 

PMID- 23875700
TI  - Biomimetic crystalline actuators: structure-kinematic aspects of the self
      actuation and motility of thermosalient crystals.
AB  - While self-actuation and motility are habitual for humans and nonsessile animals,
      they are hardly intuitive for simple, lifeless, homogeneous objects. Among
      mechanically responsive materials, the few accidentally discovered examples of
      crystals that when heated suddenly jump, propelling themselves to distances that
      can reach thousands of times their own size in less than 1 ms, provide the most
      impressive display of the conversion of heat into mechanical work. Such
      thermosalient crystals are biomimetic, nonpolymeric self-actuators par
      excellence. Yet, due to the exclusivity and incongruity of the phenomenon, as
      well as because of the unavailability of ready analytical methodology for its
      characterization, the reasons behind this colossal self-actuation remain
      unexplained. Aimed at unraveling the mechanistic aspects of the related
      processes, herein we establish the first systematic assessment of the interplay
      among the thermodynamic, kinematic, structural, and macroscopic factors driving
      the thermosalient phenomenon. The collective results are consistent with a latent
      but very rapid anisotropic unit cell deformation in a two-stage process that
      ultimately results in crystal explosion, separation of debris, or crystal
      reshaping. The structural perturbations point to a mechanism similar to phase
      transitions of the martensitic family. 

PMID- 23875701
TI  - Gold nanoparticles and cleavage-based dual signal amplification for
      ultrasensitive detection of silver ions.
AB  - Silver ion (Ag(+)) is a highly toxic heavy metal ion to fungi, viruses, bacteria,
      and animals. Therefore, Ag(+) monitoring in water or food resources has become
      extraordinarily important within the scope of human health. Here, we report a
      gold nanoparticles and enzyme cleavage-based dual signal amplification strategy
      for ultrasensitive detection of Ag(+) using electrochemical techniques. This
      sensing platform for Ag(+) has an extremely low detection limit of 470 fM, which
      also has satisfactory selectivity. Thus, it can be directly used in drinking
      water and lake water samples. Moreover, the strategy proposed in this work may
      have potential to be further developed as a generalized platform for the
      detection of other analytes by designing new DNA sequences for specific
      recognition. 

PMID- 23875702
TI  - Iron(II)-catalyzed asymmetric intramolecular aminohydroxylation of indoles.
AB  - An enantioselective intramolecular indole aminohydroxylation reaction is
      catalyzed by iron(II)-chiral bisoxazoline (BOX) complexes (ee up to 99%, dr >
      20:1). This discovery enables expedient asymmetric synthesis of a series of
      biologically active 3-amino oxindoles and 3-amino indolanes. 

PMID- 23875703
TI  - Involvement of the HIF-1alpha and Wnt/beta-catenin pathways in the protective
      effects of losartan on fatty liver graft with ischaemia/reperfusion injury.
AB  - Besides cardioprotective effects, the AT1R (angiotensin-II type 1 receptor)
      antagonist losartan protects the liver from IRI [IR (ischaemia/reperfusion)
      injury], but the mechanism has not been fully determined. The HIF (hypoxia
      inducible factor)-1alpha and Wnt/beta-catenin signalling pathways have been
      reported to be involved in the mechanism of liver IRI. Therefore the aim of the
      present study was to determine whether the Wnt/HIF axis is part of the mechanism
      of the positive effect of AngII inhibition by losartan in liver IRI in rats.
      Various measurements were made in MCD/HF-NASH (methionine- and choline-deficient
      diet/high-fat-diet-induced non-alcoholic steatohepatitis) rats with liver IRI.
      Acute losartan pre-administration markedly reversed the IR-suppressed levels of
      the hepatic-protective factors IL (interleukin)-6, IFN (interferon)-gamma, Wnt3a,
      beta-catenin and HIF-1alpha, and decreased hepatic blood flow and IR-elevated
      serum ALT (alanine aminotransferase), hepatic TNF (tumour necrosis factor)-alpha,
      IL-1alpha, hepatic congestion, vacuolization and necrosis, hepatic Suzuki IRI
      scores, necrotic index and levels of TBARS (thiobarbituric acid-reacting
      substances) in MCD/HF-NASH rats. Furthermore, acute Wnt3a pre-treatment
      significantly inhibited IR-elevated serum ALT, hepatic Suzuki IRI scores and
      TBARS, and restored the IR-depleted beta-catenin/HIF-1alpha activity in MCD/HF
      NASH rats. Simultaneous acute sFRP2 (secreted frizzled-related protein 2; a Wnt3a
      inhibitor) pre-treatment eliminated the losartan-related beneficial effects in
      MCD/HF-NASH rats with liver IRI, which was accompanied by a decrease in hepatic
      HIF-1alpha/beta-catenin activity. Losartan-induced up-regulation of HIF-1alpha
      and Wnt/beta-catenin signalling was associated with the recovery of IR-inhibited
      hepatic Bcl-2, Mn-SOD (manganese superoxide), Cu/Zn-SOD (copper/zinc superoxide)
      and GSH levels, and the suppression of IR-increased hepatic catalase and caspase
      3/caspase 8 levels in MCD/HF-NASH rats. In conclusion, up-regulation of the HIF
      1alpha and Wnt/beta-catenin signalling pathways are part of the mechanism of the
      positive effects of losartan-related AngII inhibition in MCD/HF-NASH rats with
      liver IRI. Our study highlights the potential of the dual-organ protective agent
      losartan in NASH patients with steatotic livers and cardiovascular risk.

PMID- 23875704
TI  - Systems resilience for multihazard environments: definition, metrics, and
      valuation for decision making.
AB  - The United Nations Office for Disaster Risk Reduction reported that the 2011
      natural disasters, including the earthquake and tsunami that struck Japan,
      resulted in $366 billion in direct damages and 29,782 fatalities worldwide.
      Storms and floods accounted for up to 70% of the 302 natural disasters worldwide
      in 2011, with earthquakes producing the greatest number of fatalities. Average
      annual losses in the United States amount to about $55 billion. Enhancing
      community and system resilience could lead to massive savings through risk
      reduction and expeditious recovery. The rational management of such reduction and
      recovery is facilitated by an appropriate definition of resilience and associated
      metrics. In this article, a resilience definition is provided that meets a set of
      requirements with clear relationships to the metrics of the relevant abstract
      notions of reliability and risk. Those metrics also meet logically consistent
      requirements drawn from measure theory, and provide a sound basis for the
      development of effective decision-making tools for multihazard environments.
      Improving the resiliency of a system to meet target levels requires the
      examination of system enhancement alternatives in economic terms, within a
      decision-making framework. Relevant decision analysis methods would typically
      require the examination of resilience based on its valuation by society at large.
      The article provides methods for valuation and benefit-cost analysis based on
      concepts from risk analysis and management. 

PMID- 23875705
TI  - Effects of VMAT2 inhibitors lobeline and GZ-793A on methamphetamine-induced
      changes in dopamine release, metabolism and synthesis in vivo.
AB  - Vesicular monoamine transporter-2 (VMAT2) inhibitors reduce methamphetamine
      (METH) reward in rats. The current study determined the effects of VMAT2
      inhibitors lobeline (LOB; 1 or 3 mg/kg) and N-(1,2R-dihydroxylpropyl)-2,6-cis
      di(4-methoxyphenethyl)piperidine hydrochloride (GZ-793A; 15 or 30 mg/kg) on METH
      induced (0.5 mg/kg, SC) changes in extracellular dopamine (DA) and its metabolite
      dihydroxyphenylacetic acid (DOPAC) in the reward-relevant nucleus accumbens (NAc)
      shell using in vivo microdialysis. The effect of GZ-793A (15 mg/kg) on DA
      synthesis in tissue also was investigated in NAc, striatum, medial prefrontal
      cortex and orbitofrontal cortex. In NAc shell, METH produced a time-dependent
      increase in extracellular DA and decrease in DOPAC. Neither LOB nor GZ-793A alone
      altered extracellular DA; however, both drugs increased extracellular DOPAC. In
      combination with METH, LOB did not alter the effects of METH on DA; however, GZ
      793A, which has greater selectivity than LOB for inhibiting VMAT2, reduced the
      duration of the METH-induced increase in extracellular DA. Both LOB and GZ-793A
      enhanced the duration of the METH-induced decrease in extracellular DOPAC. METH
      also increased tissue DA synthesis in NAc and striatum, whereas GZ-793A decreased
      synthesis; no effect of METH or GZ-793A on DA synthesis was found in medial
      prefrontal cortex or orbitofrontal cortex. These results suggest that selective
      inhibition of VMAT2 produces a time-dependent decrease in DA release in NAc shell
      as a result of alterations in tyrosine hydroxylase activity, which may play a
      role in the ability of GZ-793A to decrease METH reward.

PMID- 23875706
TI  - Intravenous administration of mesenchymal stem cells prevents angiotensin II
      induced aortic aneurysm formation in apolipoprotein E-deficient mouse.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are known to be capable of suppressing
      inflammatory responses. We previously reported that intra-abdominal implantation
      of bone marrow-derived MSCs (BM-MSCs) sheet by laparotomy attenuated angiotensin
      II (AngII)-induced aortic aneurysm (AA) growth in apolipoprotein E-deficient
      (apoE-/-) mice through anti-inflammation effects. However, cell delivery by
      laparotomy is invasive; we here demonstrated the effects of multiple intravenous
      administrations of BM-MSCs on AngII-induced AA formation. METHODS: BM-MSCs were
      isolated from femurs and tibiae of male apoE-/- mice. Experimental AA was induced
      by AngII infusion for 28 days in apoE-/- mice. Mice received weekly intravenous
      administration of BM-MSCs (n=12) or saline (n=10). After 4 weeks, AA formation
      incidence, aortic diameter, macrophage accumulation, matrix metalloproteinase
      (MMP)' activity, elastin content, and cytokines were evaluated. RESULTS: AngII
      induced AA formation in 100% of the mice in the saline group and 50% in the BM
      MSCs treatment group (P < 0.05). A significant decrease of aortic diameter was
      observed in the BM-MSCs treatment group at ascending and infrarenal levels, which
      was associated with decreased macrophage infiltration and suppressed activities
      of MMP-2 and MMP-9 in aortic tissues, as well as a preservation of elastin
      content of aortic tissues. In addition, interleukin (IL)-1beta, IL-6, and
      monocyte chemotactic protein-1 significantly decreased while insulin-like growth
      factor-1 and tissue inhibitor of metalloproteinases-2 increased in the aortic
      tissues of BM-MSCs treatment group. CONCLUSIONS: Multiple intravenous
      administrations of BM-MSCs attenuated the development of AngII-induced AA in apoE
      /- mice and may become a promising alternative therapeutic strategy for AA
      progression.

PMID- 23875708
TI  - TagDock: an efficient rigid body docking algorithm for oligomeric protein complex
      model construction and experiment planning.
AB  - We report here new computational tools and strategies to efficiently generate
      three-dimensional models for oligomeric biomolecular complexes in cases where
      there is limited experimental restraint data to guide the docking calculations.
      Our computational tools are designed to rapidly and exhaustively enumerate all
      geometrically possible docking poses for an oligomeric complex, rather than
      generate detailed, atomic-resolution models. Experimental data, such as
      interatomic distance measurements, are then used to select and refine docking
      poses that are consistent with the experimental restraints. Our computational
      toolkit is designed for use with sparse data sets to generate intermediate
      resolution docking models, and utilizes distance difference matrix analysis to
      identify further restraint measurements that will provide maximum additional
      structural refinement. Thus, these tools can be used to help plan optimal residue
      positions for probe incorporation in labor-intensive biophysical experiments such
      as chemical cross-linking, electron paramagnetic resonance, or Forster resonance
      energy transfer spectroscopy studies. We present benchmark results for docking
      the collection of all 176 heterodimer protein complexes from the ZDOCK database,
      as well as a protein homodimer with recently collected experimental distance
      restraints, to illustrate the toolkit's capabilities and performance, and to
      demonstrate how distance difference matrix analysis can automatically identify
      and prioritize additional restraint measurements that allow us to rapidly
      optimize docking poses. 

PMID- 23875709
TI  - RE-LYing on dabigatran for periprocedural anticoagulation: is it safe?

PMID- 23875707
TI  - Comparison of genotypic and phenotypic HIV type 1 tropism assay: results from the
      screening samples of Cenicriviroc Study 202, a randomized phase II trial in
      treatment-naive subjects.
AB  - Cenicriviroc is a once-daily oral CCR5/CCR2 antagonist in development for
      treatment of HIV infection. CVC Study 202 (652-2-202; NCT01338883) excluded
      treatment-naive subjects demonstrated to harbor non-R5 (CXCR4-tropic or dual
      mixed) tropic HIV-1 by either genotypic or phenotypic tropism testing. Here we
      compare the results of genotypic and phenotypic tropism testing in Study 202. A
      total of 304 subjects screened had paired genotypic and phenotypic results.
      Genotypic tropism testing (GTT) incorporated triplicate population sequencing
      using the geno2pheno algorithm and the PSSM algorithm, followed by ultradeep
      sequencing (UDS) for samples with R5 results. All samples were further evaluated
      with a phenotypic test, the enhanced-sensitivity Trofile assay (ESTA).
      Concordance between GTT and ESTA was 80% and increased to 84% when only
      geno2pheno was used for triplicate population sequencing. GTT (geno2pheno)
      classified 18% of the samples as non-R5 compared to 16% by ESTA. Only one-third
      of samples with non-R5 results by either test were classified as non-R5 by both
      tests. Median CD4((+)) cell counts were lower in patients with concordant non-R5
      results by UDS and ESTA than in subjects with an R5 result by either assay
      (p=0.0004). UDS detected non-R5 virus in an additional 27/304 subjects (median
      15% non-R5, interquartile range: 3.7-62%) with R5 results by ESTA. In conclusion,
      the geno2pheno algorithm improves concordance of GTT with a clinically validated
      phenotypic tropism assay as does the use of UDS. These findings provide support
      for recent guidelines indicating that genotypic tropism testing may be considered
      as an alternative to phenotypic testing.

PMID- 23875710
TI  - Selective constraint, background selection, and mutation accumulation variability
      within and between human populations.
AB  - BACKGROUND: Regions of the genome that are under evolutionary constraint across
      multiple species have previously been used to identify functional sequences in
      the human genome. Furthermore, it is known that there is an inverse relationship
      between evolutionary constraint and the allele frequency of a mutation
      segregating in human populations, implying a direct relationship between
      interspecies divergence and fitness in humans. Here we utilise this relationship
      to test differences in the accumulation of putatively deleterious mutations both
      between populations and on the individual level. RESULTS: Using whole genome and
      exome sequencing data from Phase 1 of the 1000 Genome Project for 1,092
      individuals from 14 worldwide populations we show that minor allele frequency
      (MAF) varies as a function of constraint around both coding regions and non
      coding sites genome-wide, implying that negative, rather than positive, selection
      primarily drives the distribution of alleles among individuals via background
      selection. We find a strong relationship between effective population size and
      the depth of depression in MAF around the most conserved genes, suggesting that
      populations with smaller effective size are carrying more deleterious mutations,
      which also translates into higher genetic load when considering the number of
      putatively deleterious alleles segregating within each population. Finally, given
      the extreme richness of the data, we are now able to classify individual genomes
      by the accumulation of mutations at functional sites using high coverage 1000
      Genomes data. Using this approach we detect differences between 'healthy'
      individuals within populations for the distributions of putatively deleterious
      rare alleles they are carrying. CONCLUSIONS: These findings demonstrate the
      extent of background selection in the human genome and highlight the role of
      population history in shaping patterns of diversity between human individuals.
      Furthermore, we provide a framework for the utility of personal genomic data for
      the study of genetic fitness and diseases.

PMID- 23875711
TI  - Postpartum smoking relapse among women who quit during pregnancy: cross-sectional
      study in Japan.
AB  - AIM: To determine the postpartum smoking relapse rate among women in Japan who
      quit smoking during pregnancy and to clarify factors related to smoking relapse.
      METHODS: A self-administered questionnaire survey was conducted as a cross
      sectional study of all mothers of children who underwent health checkups after
      birth in randomly selected municipalities in Japan from May to July 2009. Using
      valid data of 20,601 mothers, smoking rate was calculated. In addition, chi(2) 
      test and multiple logistic regression analysis were used to clarify related
      factors to the smoking relapse. RESULTS: The smoking rates among women were 15.8%
      at the time when they became pregnant, 5.1% during pregnancy and 11.3% after
      giving birth. Among women who smoked at the time they became pregnant, the
      smoking rate during pregnancy was 31.1%. Among women who quit smoking during
      pregnancy, the postpartum smoking relapse rate was 41.0%. The odds ratios (95%
      confidence interval) for factors in smoking relapse were 0.72 (0.60-0.88) for
      women spending time with their child in a relaxed mood, 0.67 (0.47-0.94) for
      women having someone to talk to on the Internet about childrearing, 1.94 (1.60
      2.35) for women who worked and 3.37 (2.61-4.35) for women whose partner smoked
      after they gave birth. CONCLUSION: It is hoped that future research will
      establish methods to further support smoking cessation and the continuation of
      smoking cessation after childbirth, and develop mechanisms to spread knowledge
      about the harm of smoking in society and encourage women not to start.

PMID- 23875712
TI  - Coat color genotypes and risk and severity of melanoma in gray quarter horses.
AB  - BACKGROUND: Both graying and melanoma formation in horses have recently been
      linked to a duplication in the STX17 gene. This duplication, as well as a
      mutation in the ASIP gene that increases MC1R pathway signaling, affects melanoma
      risk and severity in gray horses. OBJECTIVE: To determine if melanoma
      susceptibility in gray Quarter Horses (QH) is lower than gray horses from other
      breeds because of decreased MC1R signaling resulting from a high incidence of the
      MC1R chestnut coat color allele in the QH population. ANIMALS: A total of 335
      gray QH with and without dermal melanomas. METHODS: Blood or hair root samples
      were collected from all horses for DNA extraction and genotyping for STX17, ASIP,
      and MC1R genotypes. Age, sex, and external melanoma presence and grade were
      recorded. The effect of age and genotype on melanoma presence and severity was
      evaluated by candidate gene association. RESULTS: Melanoma prevalence (16%) and
      grade (0.35) in this QH cohort was lower than that reported in other breeds. Age
      was significantly associated with melanoma prevalence (P = 5.28 * 10(-11)) and
      severity (P = 2.2 * 10(-13)). No significant effect of MC1R genotype on melanoma
      prevalence or severity was identified. An effect of ASIP genotype on melanoma
      risk was not detected. Low STX17 homozygosity precluded evaluation of the gray
      allele effect. CONCLUSION AND CLINICAL IMPORTANCE: Melanoma prevalence and
      severity is lower in this population of gray QH than what is reported in other
      breeds. This could be because of the infrequent STX17 homozygosity, a mitigating
      effect of the MC1R mutation on ASIP potentiation of melanoma, other genes in the
      MC1R signaling pathway, or differences in breed genetic background.

PMID- 23875713
TI  - Molecular products from the thermal degradation of glutamic acid.
AB  - The thermal behavior of glutamic acid was investigated in N2 and 4% O2 in N2
      under flow reactor conditions at a constant residence time of 0.2 s, within a
      total pyrolysis time of 3 min at 1 atm. The identification of the main pyrolysis
      products has been reported. Accordingly, the principal products for pyrolysis in
      order of decreasing abundance were succinimide, pyrrole, acetonitrile, and 2
      pyrrolidone. For oxidative pyrolysis, the main products were succinimide,
      propiolactone, ethanol, and hydrogen cyanide. Whereas benzene, toluene, and a few
      low molecular weight hydrocarbons (propene, propane, 1-butene, and 2-butene) were
      detected during pyrolysis, no polycyclic aromatic hydrocarbons (PAHs) were
      detected. Oxidative pyrolysis yielded low molecular weight hydrocarbon products
      in trace amounts. The mechanistic channels describing the formation of the major
      product succinimide have been explored. The detection of succinimide (major
      product) and maleimide (minor product) from the thermal decomposition of glutamic
      acid has been reported for the first time in this study. Toxicological
      implications of some reaction products (HCN, acetonitrile, and acyrolnitrile),
      which are believed to form during heat treatment of food, tobacco burning, and
      drug processing, have been discussed in relation to the thermal degradation of
      glutamic acid. 

PMID- 23875715
TI  - A case of orbital Rosai-Dorfman disease with IgG4 positive plasma cells.
AB  - A case of a 9-year-old Black African male with right-sided proptosis is
      presented. The clinical interpretation was that of orbital rhabdomyosarcoma and
      an incisional biopsy was performed. This revealed the typical features of Rosai
      Dorfman disease, featuring S100 positive non-Langerhans histiocytes with
      emperipolesis. There were also numerous plasma cells in the biopsy, in the more
      fibrotic areas. More than 40% of these plasma cells were positive for IgG4. This
      case represents the first case in the orbit to make the association of IgG4
      plasma cell positivity with Rosai-Dorfman disease. Potential associations are
      discussed, and the relevance of this finding to ophthalmic pathology
      interpretation and differential diagnosis are highighted.

PMID- 23875714
TI  - Remarkably fast coupled folding and binding of the intrinsically disordered
      transactivation domain of cMyb to CBP KIX.
AB  - Association rates for interactions between folded proteins have been investigated
      extensively, allowing the development of computational and theoretical prediction
      methods. Less is known about association rates for complexes where one or more
      partner is initially disordered, despite much speculation about how they may
      compare to those for folded proteins. We have attached a fluorophore to the N
      terminus of the 25 amino acid cMyb peptide used previously in NMR and equilibrium
      studies (termed FITC-cMyb), and used this to monitor the kinetics of its
      interaction with the KIX protein. We have investigated the ionic strength and
      temperature dependence of the kinetics, and conclude that the association process
      is extremely fast, apparently exceeding the rates predicted by formulations
      applicable to interactions between pairs of folded proteins. This is despite the
      fact that not all collisions result in complex formation (there is an observable
      activation energy for the association process). We propose that this is partially
      a result of the disordered nature of the FITC-cMyb peptide itself. 

PMID- 23875716
TI  - Lung function and respiratory symptoms in association with mortality: The HUNT
      Study.
AB  - Whether respiratory symptoms are associated with mortality independent of lung
      function is unclear. The authors explored the association of the exposures i)
      lung function, ii) respiratory symptoms, and iii) lung function and respiratory
      symptoms combined, with the outcomes all-cause and cardiovascular mortality. The
      study included 10,491 adults who participated in the Nord-Trondelag Health Study
      (HUNT) Lung Study in 1995-1997 and were followed through 2009. Cox regression was
      used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals for
      all-cause and cardiovascular mortality associated with pre-bronchodilator%
      predicted forced expiratory volume in 1 second (ppFEV1), chronic obstructive
      pulmonary disease (COPD) grades, and respiratory symptoms (chronic bronchitis,
      wheeze, and levels of dyspnoea). Lung function was inversely associated with all
      cause mortality. Compared to ppFEV1 >=100, ppFEV1 <50 increased the HR to 6.85
      (4.46-10.52) in women and 3.88 (2.60-5.79) in men. Correspondingly, compared to
      normal airflow, COPD grade 3 or 4 increased the HR to 6.50 (4.33-9.75) in women
      and 3.57 (2.60-4.91) in men. Of the respiratory symptoms, only dyspnoea when
      walking remained associated with all-cause mortality after controlling for lung
      function (HR 1.73 [1.04-2.89] in women and 1.57 [1.04-2.36] in men). Analyses of
      lung function and dyspnoea when walking as a combined exposure further supported
      this finding. Overall, associations between lung function and cardiovascular
      mortality were weaker, and respiratory symptoms were not associated with
      cardiovascular mortality. In conclusion, lung function was inversely associated
      with all-cause and cardiovascular mortality, and dyspnoea when walking was
      associated with all-cause mortality independent of lung function.

PMID- 23875717
TI  - Inhibition of biofilm formation and antibacterial properties of a silver nano
      coating on human dentine.
AB  - The survival of pathogenic bacteria in the oral cavity depends on their
      successful adhesion to dental surfaces and their ability to develop into
      biofilms, known as dental plaque. Bacteria from the dental plaque are responsible
      for the development of dental caries, gingivitis, periodontitis, stomatitis and
      peri-implantitis. Certain metal nanoparticles have been suggested for infection
      control and the management of the oral biofilm. Here, it is shown that
      application of a silver nano-coating directly on dentine can successfully prevent
      the biofilm formation on dentine surfaces as well as inhibit bacterial growth in
      the surrounding media. This silver nano-coating was found to be stable (>98.8%)
      and to maintain its integrity in biological fluids. Its antibacterial activity
      was compared to silver nitrate and the widely used clinical antiseptic,
      chlorhexidine. The bacterial growth and cell viability were quantitatively
      assessed by measuring the turbidity, proportion of live and dead cells and
      lactate production. All three bioassays showed that silver nanoparticles and
      silver nitrate dentine coatings were equally highly bactericidal (>99.5%), while
      inhibiting bacterial adhesion. However, the latter caused significant dentine
      discolouration (DeltaE* = 50.3). The chlorhexidine coating showed no
      antibacterial effect. Thus, silver nanoparticles may be a viable alternative to
      both chlorhexidine and silver nitrate, protecting from dental plaque and
      secondary caries when applied as a dentine coating, while they may provide the
      platform for creating anti-biofilm surfaces in medical devices and other
      biomedical applications.

PMID- 23875718
TI  - Long-term effects of a nurse-led group and individual patient education programme
      for patients with chronic inflammatory polyarthritis - a randomised controlled
      trial.
AB  - AIMS AND OBJECTIVES: To investigate the long-term effect of a nurse-led hospital
      based patient education programme combining group and individual education for
      patients with chronic inflammatory polyarthritis. BACKGROUND: Patient education
      interventions have shown short-term effects, but few studies have investigated
      whether the effects are sustained for a longer period. DESIGN: Randomised
      controlled trial. METHODS: Patients with rheumatoid arthritis, psoriatic
      arthritis and unspecified polyarthritis were randomised to the intervention group
      (n = 71) or a waiting list (n = 70). Primary outcomes were as follows: Global
      Well-Being and the Arthritis Self-Efficacy Other Symptoms Subscale. Secondary
      outcomes were as follows: patient activation, physical and psychological health
      status, patients' educational needs and a Disease Activity Score (DAS28-3).
      RESULTS: The intervention group had a statistically significant higher global
      well-being than the controls after 12 months, mean change score 8.2 (95% CI, 1.6
      14.8; p-value = 0.015), but not in the Arthritis Self-Efficacy Other Symptoms
      Subscale, mean change score 2.6 (95% CI, -1.8 to 7.1; p-value = 0.245). Within
      each group, analyses showed a statistically significant improvement in DAS28-3,
      mean change -0.3 (95% CI, -0.5 to -0.1; p-value = 0.001), in the intervention
      group from baseline to 12 months, but not in the controls. The controls had a
      statistically significant deterioration in the Arthritis Self-Efficacy Other
      Symptoms Subscale, mean change -5.0 (95% CI, -8.6 to -1.3; p-value = 0.008),
      Arthritis Impact Measurement Scales - 2 Social, mean change 0.3 (95% CI, 0.1-0.5;
      p-value = 0.008), and Hospital Anxiety and Depression Scale total, mean change
      1.4 (95% CI, 0.3-2.5; p-value = 0.013). CONCLUSION: A combination of group and
      individual patient education has a long-term effect on patients' global well
      being. RELEVANCE TO CLINICAL PRACTICE: Nurses should consider whether a
      combination of group and individual patient education for patients with chronic
      inflammatory polyarthritis is an alternative in their clinical practice. This
      combination is less time-consuming for the patients, and it includes the benefit
      of group learning in addition to focusing on patient's individual educational
      needs.

PMID- 23875719
TI  - Water radiolysis in exchanged-montmorillonites: the H2 production mechanisms.
AB  - The radiolysis of water confined in montmorillonites is studied as a function of
      the composition of the montmorillonite, the nature of the exchangeable cation,
      and the relative humidity by following the H2 production under electron
      irradiation. It is shown that the main factor influencing this H2 production is
      the water amount in the interlayer space. The effect of the exchangeable cation
      is linked to its hydration enthalpy. When the water amount is high enough to get
      a basal distance higher than 1.3 nm, then a total energy transfer from the
      montmorillonite sheets to the interlayer space occurs, and the H2 production
      measured is very similar to the one obtained in bulk water. For a basal distance
      smaller than 1.3 nm, the H2 production increases with the relative humidity and
      thus with the water amount. Lastly, electron paramagnetic resonance measurements
      evidence the formation of a new defect induced by ionizing radiation. It consists
      of a hydrogen radical (H2 precursor) trapped in the structure. This implies that
      structural hydroxyl bonds can be broken under irradiation, potentially accounting
      for the observed H2 production. 

PMID- 23875720
TI  - Importance of loading and unloading procedures for gecko-inspired controllable
      adhesives.
AB  - The importance of loading and unloading procedures has been shown in a variety of
      different methods for biological dry adhesives, such as the fibers on the feet of
      the Tokay gecko, but biomimetic dry adhesives have yet to be explored in a
      similar manner. To date, little work has systematically varied multiple
      parameters to discern the influence of the testing procedure, and the effect of
      the approach angle remains uncertain. In this study, a synthetic adhesive is
      moved in 13 individual approach and retraction angles relative to a flat
      substrate as well as 9 different shear lengths to discern how loading and
      unloading procedures influence the preload, adhesion, and shear/friction forces
      supported. The synthetic adhesive, composed of vertical 10 MUm diameter
      semicircular poly(dimethylsiloxane) fibers, is tested against a 4 mm diameter
      flat glass puck on a home-built microtribometer using both vertical approach and
      retraction tests and angled approach and retraction tests. The results show that
      near maximum adhesion and friction can be obtained for most approach and
      retraction angles, provided that a sufficient shear length is performed. The
      results also show that the reaction forces during adhesive placement can be
      significantly reduced by using specific approach angles, resulting for the
      vertical fibers in a 38-fold increase in the ratio of adhesion force to preload
      force, MU', when compared to that when using a vertical approach. These results
      can be of use to those currently researching gecko-inspired adhesives when
      designing their testing procedures and control algorithms for climbing and
      perching robots. 

PMID- 23875721
TI  - Effects of expressive writing on sexual dysfunction, depression, and PTSD in
      women with a history of childhood sexual abuse: results from a randomized
      clinical trial.
AB  - INTRODUCTION: Women with a history of childhood sexual abuse (CSA) have high
      rates of depression, posttraumatic stress disorder, and sexual problems in
      adulthood. AIM: We tested an expressive writing-based intervention for its
      effects on psychopathology, sexual function, satisfaction, and distress in women
      who have a history of CSA. METHODS: Seventy women with CSA histories completed
      five 30-minute sessions of expressive writing, either with a trauma focus or a
      sexual schema focus. MAIN OUTCOME MEASURES: Validated self-report measures of
      psychopathology and sexual function were conducted at posttreatment: 2 weeks, 1
      month, and 6 months. RESULTS: Women in both writing interventions exhibited
      improved symptoms of depression and posttraumatic stress disorder (PTSD). Women
      who were instructed to write about the impact of the abuse on their sexual schema
      were significantly more likely to recover from sexual dysfunction. CONCLUSIONS:
      Expressive writing may improve depressive and PTSD symptoms in women with CSA
      histories. Sexual schema-focused expressive writing in particular appears to
      improve sexual problems, especially for depressed women with CSA histories. Both
      treatments are accessible, cost-effective, and acceptable to patients.

PMID- 23875722
TI  - Study protocol: longitudinal study of the transition of young people with complex
      health needs from child to adult health services.
AB  - BACKGROUND: Young people with complex health needs have impairments that can
      limit their ability to carry out day-to-day activities. As well as coping with
      other developmental transitions, these young people must negotiate the transfer
      of their clinical care from child to adult services. The process of transition
      may not be smooth and both health and social outcomes may suffer.Increasingly,
      policy-makers have recognised the need to ensure a smoother transition between
      children's and adult services, with processes that are holistic, individualised,
      and person-centred; however, there is little outcome data to support proposed
      models of care. This study aims to identify the features of transitional care
      that are potentially effective and efficient for young people with complex health
      needs making their transition. METHODS/DESIGN: Longitudinal cohort study. 450
      young people aged 14 years to 18 years 11 months (with autism spectrum disorder
      and an additional mental health problem, cerebral palsy or diabetes) will be
      followed through their transition from child to adult services and will
      contribute data at baseline, 12, 24 and 36 months. We will collect data on:
      health and wellbeing outcomes (participation, quality of life, satisfaction with
      services, generic health status (EQ-5D-Y) and condition specific measure of
      disease control or management); exposure to proposed beneficial features of
      services (such as having a key worker, appropriate involvement of parents); socio
      economic characteristics of the sample; use of condition-related health and
      personal social services; preferences for the characteristics of transitional
      care.We will us regression techniques to explore how outcomes vary by exposure to
      service features and by characteristics of the young people. These data will
      populate a decision-analytic model comparing the costs and benefits of potential
      alternative ways of organising transition services.In order to better understand
      mechanisms and aid interpretation, we will undertake qualitative work with 15
      young people, including interviews, non-participant observation and diary
      collection. DISCUSSION: This study will evaluate the effect of service components
      of transitional care, rather than evaluation of specific models that may be
      unsustainable or not generalisable. It has been developed in response to numerous
      national and international calls for such evaluation.

PMID- 23875724
TI  - Distinguishing the preparation and roles of Doctor of Philosophy and Doctor of
      Nursing Practice graduates: national implications for academic curricula and
      health care systems.
AB  - Although the American Association of Colleges of Nursing was clear in defining
      the role of individuals with the Doctor of Nursing Practice (DNP) degree when it
      endorsed the DNP as the single-entry degree for advanced practice nurses in 2004,
      confusion about educational curricula to prepare DNPs continues to exist in
      academic programs throughout the United States. Further, health care systems are
      unsure about the role DNP graduates should fulfill in comparison with PhD
      prepared individuals. This article discusses the importance of DNP- and PhD
      prepared individuals in improving the quality of health care and the health of
      Americans, how best to resolve the confusion in preparation of DNP and PhD
      students, and the various roles DNP and PhD graduates should fulfill in real
      world settings. A national call to action and future implications for research,
      academia, and health care settings are highlighted.

PMID- 23875723
TI  - Bridging the gap between gene expression and metabolic phenotype via kinetic
      models.
AB  - BACKGROUND: Despite the close association between gene expression and metabolism,
      experimental evidence shows that gene expression levels alone cannot predict
      metabolic phenotypes, indicating a knowledge gap in our understanding of how
      these processes are connected. Here, we present a method that integrates
      transcriptome, fluxome, and metabolome data using kinetic models to create a
      mechanistic link between gene expression and metabolism. RESULTS: We developed a
      modeling framework to construct kinetic models that connect the transcriptional
      and metabolic responses of a cell to exogenous perturbations. The framework
      allowed us to avoid extensive experimental characterization, literature mining,
      and optimization problems by estimating most model parameters directly from
      fluxome and transcriptome data. We applied the framework to investigate how gene
      expression changes led to observed phenotypic alterations of Saccharomyces
      cerevisiae treated with weak organic acids (i.e., acetate, benzoate, propionate,
      or sorbate) and the histidine synthesis inhibitor 3-aminotriazole under steady
      state conditions. We found that the transcriptional response led to alterations
      in yeast metabolism that mimicked measured metabolic fluxes and concentration
      changes. Further analyses generated mechanistic insights of how S. cerevisiae
      responds to these stresses. In particular, these results suggest that S.
      cerevisiae uses different regulation strategies for responding to these insults:
      regulation of two reactions accounted for most of the tolerance to the four weak
      organic acids, whereas the response to 3-aminotriazole was distributed among
      multiple reactions. Moreover, we observed that the magnitude of the gene
      expression changes was not directly correlated with their effect on the ability
      of S. cerevisiae to grow under these treatments. In addition, we identified
      another potential mechanism of action of 3-aminotriazole associated with the
      depletion of tetrahydrofolate. CONCLUSIONS: Our simulation results show that the
      modeling framework provided an accurate mechanistic link between gene expression
      and cellular metabolism. The proposed method allowed us to integrate
      transcriptome, fluxome, and metabolome data to determine and interpret important
      features of the physiological response of yeast to stresses. Importantly, given
      its flexibility and robustness, our approach can be applied to investigate the
      transcriptional-metabolic response in other cellular systems of medical and
      industrial relevance.

PMID- 23875725
TI  - The Doctor of Nursing Practice: defining the next steps.
AB  - The purpose of this article is to summarize the previous articles in this special
      issue of the Journal of Nursing Education that are based on the Committee on
      Institutional Cooperation's Dean's Conference on the Doctor of Nursing Practice
      (DNP) and to identify areas of consensus, as well as areas of controversy. Areas
      of consensus include the high level of interest in DNP programs and the intent to
      expand the role of the advanced practice nurse to population health, policy, and
      leadership. Areas of controversy include the nature of the DNP product, the
      definition of clinical experiences, the nature of the capstone project, the
      outcomes of these new practitioners, and the impact on schools. Suggestions for
      achieving higher levels of consensus, including the need for respective,
      inclusive dialogue, are provided.

PMID- 23875726
TI  - Impact of Doctor of Nursing Practice education in shaping health care systems for
      the future.
AB  - The approval of the Doctor of Nursing Practice (DNP) by the American Association
      of Colleges of Nursing in 2004 and publication of The Essentials of Doctoral
      Education for Advanced Nursing Practice in 2006 promised significant benefit to
      nursing and to shaping health care systems. Currently, 229 DNP programs exist and
      more are planned. This article provides an overview of program types, graduates,
      and postgraduation placement, using Pennsylvania as an exemplar, to describe the
      potential impact of DNP education in health care systems. Nurse educators need to
      consider whether our current directions enable us to realize opportunities for
      shaping health care systems or whether we need to make course corrections. [

PMID- 23875727
TI  - Intraprofessional collaboration through an unfolding case and the just culture
      model.
AB  - The National League for Nursing (NLN) developed four unfolding cases. A
      demonstration project was created by junior- and senior-level faculty with the
      simulation specialist by modifying an NLN unfolding case to include advanced
      practice nurses. Educators desire their students to think critically but often do
      not realize that students must pass through five stages of development in
      critical thinking. The critical thinking stage theory was used by faculty to
      guide students through the unfolding case and to provide a framework for
      improvement of their critical thinking skills. Faculty also used the just culture
      model as a framework for the debriefing process. The student evaluation findings
      for all three simulations were positive. Faculty and students supported the use
      of intraprofessional teams, critical thinking theory, and the just culture
      debriefing model as effective teaching-learning strategies.

PMID- 23875728
TI  - Complementation of biotransformations with chemical C-H oxidation: copper
      catalyzed oxidation of tertiary amines in complex pharmaceuticals.
AB  - The isolation, quantitation, and characterization of drug metabolites in
      biological fluids remain challenging. Rapid access to oxidized drugs could
      facilitate metabolite identification and enable early pharmacology and toxicity
      studies. Herein, we compared biotransformations to classical and new chemical C-H
      oxidation methods using oxcarbazepine, naproxen, and an early compound hit
      (phthalazine 1). These studies illustrated the low preparative efficacy of
      biotransformations and the inability of chemical methods to oxidize complex
      pharmaceuticals. We also disclose an aerobic catalytic protocole (CuI/air) to
      oxidize tertiary amines and benzylic CH's in drugs. The reaction tolerates a
      broad range of functionalities and displays a high level of chemoselectivity,
      which is not generally explained by the strength of the C-H bonds but by the
      individual structural chemotype. This study represents a first step toward
      establishing a chemical toolkit (chemotransformations) that can selectively
      oxidize C-H bonds in complex pharmaceuticals and rapidly deliver drug
      metabolites. 

PMID- 23875729
TI  - Myths about the proton. The nature of H+ in condensed media.
AB  - Recent research has taught us that most protonated species are decidedly not well
      represented by a simple proton addition. What is the actual nature of the
      hydrogen ion (the "proton") when H(+), HA, H2A(+), and so forth are written in
      formulas, chemical equations, and acid catalyzed reactions? In condensed media,
      H(+) must be solvated and is nearly always dicoordinate, as illustrated by
      isolable bisdiethyletherate salts having H(OEt2)2(+) cations and weakly
      coordinating anions. Even carbocations such as protonated alkenes have
      significant C-H...anion hydrogen bonding that gives the active protons two
      coordinate character. Hydrogen bonding is everywhere, particularly when acids are
      involved. In contrast to the normal, asymmetric O-H...O hydrogen bonding found in
      water, ice, and proteins, short, strong, low-barrier (SSLB) H-bonding commonly
      appears when strong acids are present. Unusually low frequency IR nuOHO bands are
      a good indicator of SSLB H-bonds, and curiously, bands associated with group
      vibrations near H(+) in low-barrier H-bonding often disappear from the IR
      spectrum. Writing H3O(+) (the Eigen ion), as often appears in textbooks, might
      seem more realistic than H(+) for an ionized acid in water. However, this, too,
      is an unrealistic description of H(aq)(+). The dihydrated H(+) in the H5O2(+)
      cation (the Zundel ion) gets somewhat closer but still fails to rationalize all
      the experimental and computational data on H(aq)(+). Researchers do not
      understand the broad swath of IR absorption from H(aq)(+), known as the
      "continuous broad absorption" (cba). Theory has not reproduced the cba, but it
      appears to be the signature of delocalized protons whose motion is faster than
      the IR time scale. What does this mean for reaction mechanisms involving
      H(aq)(+)? For the past decade, the carborane acid H(CHB11Cl11) has been the
      strongest known Bronsted acid. (It is now surpassed by the fluorinated analogue
      H(CHB11F11).) Carborane acids are strong enough to protonate alkanes at room
      temperature, giving H2 and carbocations. They protonate chloroalkanes to give
      dialkylchloronium ions, which decay to carbocations. By partially protonating an
      oxonium cation, they get as close to the fabled H4O(2+) ion as can be achieved
      outside of a computer. 

PMID- 23875730
TI  - Personalized-detailed clinical model for data interoperability among clinical
      standards.
AB  - OBJECTIVE: Data interoperability among health information exchange (HIE) systems
      is a major concern for healthcare practitioners to enable provisioning of
      telemedicine-related services. Heterogeneity exists in these systems not only at
      the data level but also among different heterogeneous healthcare standards with
      which these are compliant. The relationship between healthcare organization data
      and different heterogeneous standards is necessary to achieve the goal of data
      level interoperability. We propose a personalized-detailed clinical model (P-DCM)
      approach for the generation of customized mappings that creates the necessary
      linkage between organization-conformed healthcare standards concepts and clinical
      model concepts to ensure data interoperability among HIE systems. MATERIALS AND
      METHODS: We consider electronic health record (EHR) standards, openEHR, and HL7
      CDA instances transformation using P-DCM. P-DCM concepts associated with openEHR
      and HL7 CDA help in transformation of instances among these standards. We
      investigated two datasets: (1) data of 100 diabetic patients, including 50 each
      of type 1 and type 2, from a local hospital in Korea and (2) data of a single
      Alzheimer's disease patient. P-DCMs were created for both scenarios, which
      provided the basis for deriving instances for HL7 CDA and openEHR standards.
      RESULTS: For proof of concept, we present case studies of encounter information
      for type 2 diabetes mellitus patients and monitoring of daily routine activities
      of an Alzheimer's disease patient. These reflect P-DCM-based customized mappings
      generation with openEHR and HL7 CDA standards. Customized mappings are generated
      based on the relationship of P-DCM concepts with CDA and openEHR concepts.
      CONCLUSIONS: The objective of this work is to achieve semantic data
      interoperability among heterogeneous standards. This would lead to effective
      utilization of resources and allow timely information exchange among healthcare
      systems.

PMID- 23875731
TI  - Regarding: "comparison of parent satisfaction with care for childhood obesity
      delivered face-to-face and by telemedicine".

PMID- 23875732
TI  - Oxysterol receptors and their therapeutic applications in cancer conditions.
AB  - INTRODUCTION: Oxysterols are implicated in various cellular processes. Among
      their target proteins, liver X receptors (LXRs) alpha and beta modulate the cell
      cycle in a large range of cancer cell lines. Besides their role as cholesterol
      sensors, LXRs are also involved in the proliferation/apoptosis balance regulation
      in various types of cancers. AREAS COVERED: This review covers oxysterols and
      derivatives of cholesterol as well as synthetic or natural ligands
      (agonist/antagonist) of LXRs. Most tumor cell lines are sensitive to LXR
      activation. Indeed various cancers are concerned such as prostate, breast,
      glioblastoma, colorectal, and ovary tumors, and leukemia. EXPERT OPINION:
      Developing the use of LXR ligands in human health, especially in the field of
      cancer, represents a novel and promising strategy. Despite a wide spectrum of
      applications, numerous adverse effects of LXR activation need to be solved before
      genuine clinical trials in humans. Future directions will be based on the
      engineering of selective LXRs modulators (SLiMs) as already done for nuclear
      steroid receptors.

PMID- 23875733
TI  - The composition of cigarette smoke determines inflammatory cell recruitment to
      the lung in COPD mouse models.
AB  - COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases
      and particles, most often CS (cigarette smoke), leading to emphysema, chronic
      bronchitis, mucus production and a subsequent decline in lung function. The
      disease pathogenesis is related to an abnormal CS-induced inflammatory response
      of the lungs. Similar to active (mainstream) smoking, second hand (sidestream)
      smoke exposure severely affects respiratory health. These processes can be
      studied in vivo in models of CS exposure of mice. We compared the acute
      inflammatory response of female C57BL/6 mice exposed to two concentrations [250
      and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for
      3 days and interpreted the biological effects based on physico-chemical
      differences in the gas and particulate phase composition of CS. BAL
      (bronchoalveolar lavage fluid) was obtained to perform differential cell counts
      and to measure cytokine release. Lung tissue was used to determine mRNA and
      protein expression of proinflammatory genes and to assess tissue inflammation. A
      strong acute inflammatory response characterized by neutrophilic influx,
      increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-alpha
      (tumour necrosis factor alpha), MIP-2 (macrophage inflammatory protein 2), MIP
      1alpha and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene
      expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated
      GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed
      in the mainstream model. After sidestream exposure there was a dampened
      inflammatory reaction consisting only of macrophages and diminished GM-CSF
      levels, most likely caused by elevated CO concentrations. These results
      demonstrate that the composition of CS determines the dynamics of inflammatory
      cell recruitment in COPD mouse models. Different initial inflammatory processes
      might contribute to COPD pathogenesis in significantly varying ways, thereby
      determining the outcome of the studies. 

PMID- 23875734
TI  - Bisphosphonate-related osteonecrosis of the jaws: analysis of a case series at a
      dental school.
AB  - Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is an adverse effect of
      drugs used to treat bone metabolism diseases, such as osteoporosis and bone
      metastases. The present study retrospectively evaluated the clinical
      characteristics and evolution of BRONJ cases that were diagnosed and treated at a
      dental school from 2004 to 2011. During that period, 13 patients met the criteria
      of the study among a population of 2,342 patients with oral lesions. Of the 13
      patients, 12 were females. Ten were intravenous bisphosphonate users, and nine
      had breast cancer as the primary disease. Eight mandibular cases were observed.
      Eight patients interrupted the use of the bisphosphonates temporarily during the
      treatment. Surgical treatment was conducted in 10 patients, which was associated
      with platelet-rich plasma in six cases, which led to a regression to Stage I in
      50% of these and cure in 33.3%. Of the total sample, four (30.8%) cases were
      cured, six (46.1%) regressed to Stage I, and three (23.1%) remained in Stage II
      after treatment. Dental rehabilitation occurred in seven patients. Dissemination
      of knowledge among professionals is essential for prevention and early diagnosis
      of BRONJ. Dental schools must act as reference centers and participate in the
      multidisciplinary care of bisphosphonate users.

PMID- 23875736
TI  - Defibrillation threshold testing does not predict clinical outcomes during long
      term follow-up: a meta-analysis.
AB  - BACKGROUND: Defibrillation threshold (DFT) testing at the time of implantable
      cardioverter defibrillator (ICD) implantation is widely used in clinical
      practice, but reliable data supporting its routine use are lacking. We undertook
      a meta-analysis to evaluate the efficacy of DFT testing compared to no DFT
      testing at the time of ICD implantation. METHODS: We searched the MEDLINE and
      EMBASE databases for studies evaluating the effect of DFT testing on total
      mortality and ventricular arrhythmias during follow-up. Risk ratios (RR) with 95%
      confidence intervals (CI) were calculated using random effects modeling. RESULTS:
      Eight studies involving 5,020 patients (3,068 undergoing DFT and 1,952 not
      undergoing DFT) were included. Of those, only one study was randomized. Reasons
      for not performing DFT included patient characteristics (four studies), center's
      standard practice (three studies), or randomization (one study). Median follow-up
      was 24 months. Overall, the quality of the included studies was rather poor. On
      the basis of the pooled estimate across the studies, DFT testing did not reduce
      total mortality or ventricular arrhythmias at follow-up (RR = 0.94, 95% CI 0.74
      1.21; P = 0.65 and RR = 1.19, 95% CI 0.85-1.68; P = 0.30, respectively). No
      individual study had a major impact on the estimated RR or the statistical
      significance based on a sensitivity analysis. CONCLUSION: Recognizing the limited
      quality of current studies in the area of DFT testing and outcomes, available
      data suggest that DFT testing at the time of ICD implantation does not appear to
      predict total mortality and ventricular arrhythmias during follow-up. Large
      randomized controlled trials, adequately powered to detect clinical outcomes, are
      warranted.

PMID- 23875737
TI  - Molecular trickery in soil organic matter: hidden lignin.
AB  - Binding to minerals is one mechanism crucial toward the accumulation and
      stabilization of organic matter (OM) in soils. Of the various biochemicals
      produced by plants, lignin-derived phenols are among the most surface-reactive
      compounds. However, it is not known to what extent mineral-bound lignin-derived
      phenols can be analytically assessed by alkaline CuO oxidation. We tested the
      potential irreversible binding of lignin from three litters (blue oak, foothill
      pine, annual grasses) to five minerals (ferrihydrite, goethite, kaolinite,
      illite, montmorillonite) using the CuO-oxidation technique, along with bulk
      organic carbon (OC) sorption. Up to 56% of sorbed lignin could not be extracted
      from the minerals with the CuO-oxidation technique. The composition of the
      irreversibly bound lignin component differed markedly between minerals and from
      that of the parent litter leachates, indicating different bonding strengths
      related to individual monomers and conformations. The difference in
      extractability of individual phenols suggests that abiotic processes, such as
      sorption/desorption, should be taken into account when using CuO oxidation data
      for assessing lignin turnover in mineral matrixes. However, given the apparent
      relationship between aromaticity as indicated by carbon-specific UV absorbance
      (SUVA) and bulk OC sorption, it is likely that irreversible sorption is a concern
      for any technique that addresses the broad class of aromatic/phenolic compounds
      in soils and sediments. 

PMID- 23875735
TI  - Critical role of calpain in spinal cord degeneration in Parkinson's disease.
AB  - While multiple molecular mechanisms contribute to midbrain nigrostriatal
      dopaminergic degeneration in Parkinson's disease (PD), the mechanism of damage in
      non-dopaminergic sites within the central nervous system, including the spinal
      cord, is not well-understood. Thus, to understand the comprehensive
      pathophysiology underlying this devastating disease, postmortem spinal cord
      tissue samples (cervical, thoracic, and lumbar segments) from patients with PD
      were analyzed compared to age-matched normal subjects or Alzheimer's disease for
      selective molecular markers of neurodegeneration and inflammation. Distal axonal
      degeneration, relative abundance of both sensory and motor neuron death,
      selective loss of ChAT(+) motoneurons, reactive astrogliosis, microgliosis,
      increased cycloxygenase-2 (Cox-2) expression, and infiltration of T cells were
      observed in spinal cord of PD patients compared to normal subjects. Biochemical
      analyses of spinal cord tissues revealed associated inflammatory and proteolytic
      events (elevated levels of Cox-2, expression and activity of MU- and m-calpain,
      degradation of axonal neurofilament protein, and concomitantly low levels of
      endogenous inhibitor - calpastatin) in spinal cord of PD patients. Thus,
      pathologically upregulated calpain activity in spinal cords of patients with PD
      may contribute to inflammatory response-mediated neuronal death, leading to motor
      dysfunction. We proposed calpain over-activation and calpain-calpastatin
      dysregulation driving in a cascade of inflammatory responses (microglial
      activation and T cell infiltration) and degenerative pathways culminating in
      axonal degeneration and neuronal death in spinal cord of Parkinson's disease
      patients. This may be one of the crucial mechanisms in the degenerative process. 

PMID- 23875738
TI  - Vitamin D deficiency impacts on expression of toll-like receptor-2 and cytokine
      profile: a pilot study.
AB  - BACKGROUND: Vitamin D is believed to play an important role outside the endocrine
      system in the regulation of the immune system, and in cellular proliferation and
      differentiation. The aim of the study was to investigate the impact of vitamin D
      levels on innate immunity. METHODS: Participants for this prospective,
      longitudinal study were recruited amongst otherwise healthy staff of a large
      hospital in Victoria, Australia. Those fulfilling the inclusion criteria,
      including a vitamin D level of <50 nmol/L, were supplemented. Using flow
      cytometry, expression of the innate immune receptors TLR2, TLR4 and CD86 was
      measured on peripheral blood mononuclear cells (PBMCs) collected prior to vitamin
      D treatment and then at 1 and 3 months. Additonally, PBMCs at each timepoint were
      stimulated with specific TLR ligands and resultant supernatants were assayed for
      the cytokines TNFalpha, IL-6, IFN-alpha and IP-10. RESULTS: In participants whose
      vitamin D level was >100 nmol/L post supplementation (n=11), TLR2 expression on
      PBMCs increased significantly, with no change noted in TLR4 or CD86 expression.
      Stimulation of vitamin D deficient samples with TLR ligands produced a number of
      proinflammatory cytokines, which were significantly reduced upon vitamin D
      normalisation. In patients whose levels returned to a deficient level at 3 months
      despite ongoing low-level supplementation, an increase in the pro-inflamamtory
      state returned. This suggests that vitamin D may play an important role in
      ensuring an appropriate baseline pro-inflammatory state. CONCLUSIONS: This ex
      vivo pilot study adds clinical evidence supporting a possibly important role for
      vitamin D in innate immunity. If confirmed, this unique clinical study has
      potentially significant implications for the treatment of a variety of
      inflammatory conditions, where achieving optimal vitamin D levels may help reduce
      inflammation.

PMID- 23875739
TI  - Elastin degradation products as biomarkers in alpha-1 antitrypsin deficiency:
      lastin' impact?

PMID- 23875740
TI  - Differential expression of vitamin E and selenium-responsive genes by disease
      severity in chronic obstructive pulmonary disease.
AB  - Antioxidant nutritional status is hypothesized to influence chronic obstructive
      pulmonary disease (COPD) susceptibility and progression. Although past studies
      relate antioxidants to gene expression, there are no data in patients with COPD.
      This study investigated the hypothesis that antioxidant status is compromised in
      patients with COPD, and antioxidant-responsive genes differentially express in a
      similar pattern. Lung tissue samples from patients with COPD were assayed for
      vitamin E and gene expression. Selenium and vitamin E were assayed in
      corresponding plasma samples. Discovery based genome-wide expression analysis
      compared moderate, severe, and very severe COPD (GOLD II-IV) patients to mild and
      at-risk/normal (GOLD 0-I). Hypotheses-driven analyses assessed differential gene
      expression by disease severity for vitamin E-responsive and selenium-responsive
      genes. GOLD II-IV COPD patients had 30% lower lung tissue vitamin E levels
      compared to GOLD 0-I participants (p = 0.0082). No statistically significant
      genome-wide differences in expression by disease severity were identified.
      Hypothesis-driven analyses of 109 genes found 16 genes differentially expressed
      (padjusted < 0.05) by disease severity including 6 selenium-responsive genes
      (range in fold-change -1.39 to 2.25), 6 vitamin E-responsive genes (fold-change 
      2.30 to 1.51), and 4 COPD-associated genes. Lung tissue vitamin E in patients
      with COPD was associated with disease severity and vitamin E-responsive genes
      were differentially expressed by disease severity. Although nutritional status is
      hypothesized to contribute to COPD risk, and is of therapeutic interest, evidence
      to date is mainly observational. The findings reported herein are novel, and
      support a role of vitamin E in COPD progression.

PMID- 23875742
TI  - Perceptions and attitudes toward the use of nebulized therapy for COPD: patient
      and caregiver perspectives.
AB  - Although delivery of medications through nebulization is effective for patients
      with COPD, nebulization is often perceived negatively. This survey evaluated
      patient and caregiver attitudes and perceptions related to the use of
      nebulization for the management of COPD. A total of 400 patients and a separate
      population of 400 caregivers were randomly selected and interviewed via
      telephone. Responses were assessed on the basis of 4 domains: health of patients
      with COPD, satisfaction with nebulization therapy, benefits and challenges, and
      the caregiver role. Most patients (58%) self-classified their COPD as "mild to
      moderate," with shortness of breath upon minimal to moderate exertion; caregivers
      reported similar findings. The majority of patients and caregivers (89% and 92%,
      respectively) were "generally satisfied with their (or their friend's or family
      member's) current nebulized treatment." Based on their personal experiences, 80%
      of patients and caregivers reported that using a nebulizer was better than using
      only an inhaler. Patients and caregivers agreed (79% and 85%, respectively) that
      the benefits of nebulization therapy outweighed the difficulties or
      inconveniences. Patients believed that their overall quality of life had improved
      since beginning nebulization (75%) and that nebulization better enabled their
      caregiver to provide care (77%); caregivers echoed this sentiment. Overall, this
      survey demonstrated that an overwhelming majority of patients and caregivers were
      satisfied with nebulization therapy, reporting benefits in symptom relief, ease
      of use, and improved quality of life.

PMID- 23875741
TI  - Combined therapy with tiotropium and formoterol in chronic obstructive pulmonary
      disease: effect on the 6-minute walk test.
AB  - Combined therapy with tiotropium and long-acting beta 2 agonists confers
      additional improvement in symptoms, lung function and aspects of health-related
      quality of life (QOL) compared with each drug alone in patients with COPD.
      However, the efficacy of combined therapy on walking distance, a surrogate
      measure of daily functional activity and morbidity remains unclear. The aim was,
      therefore, to quantify the benefit of this therapy on the six minute walk test.
      Secondary outcomes included change in lung function, symptoms, the BODE index and
      QOL. In a double-blind, crossover study, 38 participants with moderate to severe
      COPD on tiotropium were randomised to receive either formoterol or placebo for 6
      weeks. Following a 2-week washout period, participants crossed over to the
      alternate arm of therapy for a further 6 weeks. Thirty-six participants, with an
      average age of 64.3 years and FEV1 predicted of 53%, completed the study.
      Combined therapy improved walking distance by a mean of 36 metres [95% CI: 2.4,
      70.1; p = 0.04] compared with tiotropium. FEV1 increased in both groups (160 mL
      combination therapy versus 30 mL tiotropium) with a mean difference of 110 mL
      (95% CI: -100, 320; p = 0.07) between groups, These findings further support the
      emerging advantages of combined therapy in COPD. Australian New Zealand Clinical
      Trials.

PMID- 23875743
TI  - Prevalence of airflow obstruction in nonsmoking older individuals using different
      spirometric criteria: the AGES Reykjavik Study.
AB  - BACKGROUND: The prevalence and characteristics of airway obstruction in older
      individuals varies widely with the definition used. We used a random sample of
      never smoking older population in Iceland to compare the prevalence and clinical
      profile of subjects diagnosed with Chronic Obstructive Pulmonary Disease (COPD)
      based on different spirometric criteria. MATERIAL AND METHODS: The study uses
      data from the Age, Gene/Environment Susceptibility-Reykjavik Study, comprising
      survivors from the Reykjavik Study. Procedures included standardized
      questionnaires and pre-bronchodilator spirometry for measurement of forced
      expiratory volume in one second (FEV1) and forced vital capacity (FVC). RESULTS:
      Total of 495 individuals (150 men and 345 women) met study criteria. Mean age 77
      years (range 66-92 years) using fixed ratio (FEV1/FVC < 70%) up to 29% of the
      population were diagnosed with COPD Stage I. The prevalence of COPD increased
      with age. Only 7 among 495 (1.4%) were diagnosed with COPD using FEV1/FVC LLN and
      FEV1 LLN. CONCLUSION: Application of the GOLD criteria for diagnosis of COPD in
      older lifelong never smoking subjects identifies a substantial number of non
      symptomatic subjects as having COPD. If airway obstruction is defined by FEV1/FVC
      and FEV1 being below the LLN using appropriate reference equations, only very few
      non-smoking older individuals fulfill the criteria for COPD.

PMID- 23875744
TI  - The COPD Pipeline XXIII.

PMID- 23875745
TI  - Computed tomography biomarkers of pulmonary emphysema.

PMID- 23875747
TI  - A ratiometric near-infrared fluorescent probe for hydrazine and its in vivo
      applications.
AB  - Based on modulation of the conjugated polymethine pi-electron system of a cyanine
      dye derivative, a ratiometric near-infared fluorescent probe (Cy7A) for hydrazine
      (N2H4) has been designed and synthesized. Cy7A can be selectively
      hydrazinolysized with great changes in its fluorescent excitation/emission
      profiles, which makes it possible to detect N2H4 in water samples and living
      cells and, for the first time, visualize N2H4 in living mice. 

PMID- 23875748
TI  - Prevalence of effusion in the tympanic cavity in dogs with dysfunction of the
      trigeminal nerve: 18 cases (2004-2013).
AB  - BACKGROUND: Animals with disorders involving the trigeminal nerve or its nuclei
      in the brainstem can have effusion in the tympanic cavity ipsilateral to the side
      of the neurological deficits. The tensor veli palatini muscle (TVP), innervated
      by the mandibular branch of the trigeminal nerve, opens the pharyngeal orifice of
      the auditory tube. With denervation of the TVP, dysfunction of the auditory tube
      may occur, which could lead to effusion. HYPOTHESIS/OBJECTIVES: To determine the
      prevalence of effusion in the tympanic cavity in dogs with disorders involving
      the trigeminal nerve. ANIMALS: Eighteen client-owned dogs were evaluated
      retrospectively. METHODS: Retrospective study. RESULTS: Diagnostic imaging
      databases were searched for dogs having undergone magnetic resonance imaging
      (MRI) evaluation for signs referable to dysfunction of the trigeminal nerve.
      Signalment and neurological examination findings were recorded. The MRI study was
      evaluated for the presence or absence of effusion. MRI characteristics of the
      affected trigeminal nerve and the muscles of mastication were recorded. Based on
      the location of the trigeminal nerve lesion, dogs were divided into three
      categories: brainstem, trigeminal canal, or extracranial. Eighteen dogs met the
      inclusion criteria. Six of 18 dogs (33%) had effusion in the tympanic cavity
      ipsilateral to the affected trigeminal nerve. CONCLUSION AND CLINICAL IMPORTANCE:
      A substantial proportion of dogs with a lesion affecting the trigeminal nerve had
      effusion in the tympanic cavity. This finding likely represents denervation of
      the TVP muscle, which may have led to dysfunction of the auditory tube.

PMID- 23875749
TI  - Interaction of inducible nitric oxide synthase with rac2 regulates reactive
      oxygen and nitrogen species generation in the human neutrophil phagosomes:
      implication in microbial killing.
AB  - AIMS: Present study explores importance of inducible nitric oxide synthase (iNOS)
      and its interaction with Rac2 in reactive oxygen species (ROS)/reactive nitrogen
      species (RNS) generation, protein-nitration and in microbial killing by
      neutrophils. RESULTS: The iNOS transcript and protein were constitutively present
      in human as well as in mice neutrophils. iNOS protein was found in cytosol,
      granules containing elastase and gelatinase, and in other subcellular organelles
      in resting human neutrophils. After phagocytosis of bovine serum albumin (BSA)
      coated beads, both human and mice neutrophils showed significant elevation in
      superoxide radicals, nitric oxide (NO), ROS/RNS and consequent BSA nitration.
      These responses were significantly reduced in presence of iNOS, NADPH oxidase
      (NOX), myeloperoxidase or Rac inhibitors, as well as in iNOS, Nox2 and Rac2
      silenced human or iNOS-knockout mice neutrophils. Complex formed on interaction
      of iNOS with Rac2 coprecipitated with anti-Rac2, predominantly in cytosol in
      resting human neutrophils, while iNOS-Rac2 complex translocated to phagosomes
      after phagocytosis. This was accompanied by generation of superoxide radicals,
      NO, ROS/RNS and consequent BSA-nitration. Importance of Rac2 in iNOS mediated NO
      formation and microbial killing was confirmed by pretreatment of mice with Rac
      inhibitor, NSC23766 that significantly abrogated NO release and microbial killing
      in vivo. INNOVATION: Present study highlights previously undefined role of Rac2
      iNOS interaction, in translocation of iNOS to phagosomal compartment and
      consequent NO, superoxide radicals, ROS/RNS generation, BSA nitration and
      microbial killing. CONCLUSIONS: Altogether results obtained demonstrate the role
      of iNOS in NO and ROS/RNS generation, after phagocytosis of coated latex beads by
      human polymorphonuclear neutrophils. These studies imply functional importance of
      iNOS and its interaction with Rac2 in pathogen killing by the neutrophils.

PMID- 23875750
TI  - Polymethylmethacrylate open tubular ion exchange columns: nondestructive
      measurement of very small ion exchange capacities.
AB  - We describe an approach to prepare an open tubular ion exchange (OTIE) column by
      coating a monolayer of anion exchange nanoparticle to a 16-20 MUm bore
      polymethylmethacrylate (PMMA) capillary. The latex nanoparticle was
      electrostatically attached to carboxylate groups on the inner wall of capillary,
      pretreated with strong base for hydrolyzing the ester. Several approaches to
      nondestructively measure ion exchange capacities (IEC) of the columns were
      examined: (a) adsorption-desorption of an intensely fluorescent ion, e.g.
      fluorescein, and off-line fluorometry, (b) loading a weakly retained ion (e.g.,
      IO3(-)), frontal displacement by a strongly bound ion (e.g., Cl(-)), and online
      optical or conductometric boundary detection, and (c) similar to the above except
      displacement being accompanied by reaction (e.g., acid-base titration). To our
      knowledge, this is the first time on-column titration has been used to measure
      capacities. By using different pH displacer solutions, we demonstrate for the
      first time the possibility of pKa-differentiated ion exchange capacity
      measurements. The cation exchange capacity of bare PMMA capillaries was on the
      order of 1 pequiv/mm(2) with little dependence on time and temperature of
      hydrolysis conditions. After AS18 latex coating, the strong base anion exchange
      capacity was on the order of 10 pequiv/mm(2), very close to what would be
      estimated on the basis of monolayer coverage of the surface by individual latex
      particles. The latex used contained a significant, additional amount of weak base
      character, about the same as the strong base ion exchange capacity. 

PMID- 23875751
TI  - Structure and dynamics of soft repulsive colloidal suspensions in the vicinity of
      the glass transition.
AB  - We use a combination of different scattering techniques and rheology to highlight
      the link between structure and dynamics of dense aqueous suspensions of soft
      repulsive colloids in the vicinity of a glass transition. Three different latex
      formulations with an increasing amount of the hydrophilic component resulting in
      either purely electrostatically or electrosterically stabilized suspensions are
      investigated. From the analysis of the static structure factor measured by small
      angle X-ray scattering, we derive an effective volume fraction that includes
      contributions from interparticle interactions. We further investigate the
      dynamics of the suspensions using 3D cross-correlation dynamic light scattering
      (3DDLS) and rheology. We analyze the data using an effective hard sphere model
      and in particular compare the linear viscoelasticity and flow behavior to the
      predictions of mode coupling theory, which accounts for a purely kinetic glass
      transition determined by the equilibrium structure factor. We demonstrate that
      seemingly very different colloidal systems exhibit the same generic behavior when
      the effects from interparticle interactions are incorporated using an effective
      volume fraction description. 

PMID- 23875752
TI  - Preventing postpartum haemorrhage: active management of the third stage of
      labour.
AB  - AIMS AND OBJECTIVES: To review scientific publications on health to identify the
      main practices used for the active management of the third stage of vaginal
      labour and to assess their effectiveness in preventing postpartum haemorrhage.
      BACKGROUND: According to the World Health Organization (WHO Recommendations for
      the Prevention of Postpartum Haemorrhage, 2007. WHO Document Production Services,
      Geneva), postpartum haemorrhage is considered to be the cause of a quarter of
      maternal morbidity and mortality rates worldwide. In an attempt to reduce the
      risk of haemorrhage, a group of interventions have been introduced into clinical
      practice that constitute active management conduct during the third stage of
      labour and are recommended by the international organisations. DESIGN AND
      METHODS: An integrative literature review of studies on the subject in question,
      indexed in databases of health between the years 2006-2012, was conducted. The
      analysis included 13 articles, six of which were original articles and seven of
      which were literature reviews. RESULTS: Based on our data analysis, we found that
      most studies supported the effectiveness of active management in reducing the
      risk of haemorrhage, in the immediate postpartum period. Despite the fact that
      active management practices for the third stage of labour differ in their
      specific elements, in the majority of the selected studies, the interventions
      followed those recommended by the international organisations. CONCLUSIONS: The
      results of this review of management practices supported active management of the
      third stage of labour to prevent postpartum haemorrhage, with five main forms of
      intervention: administration of oxytocin, delayed clamping of umbilical cord,
      draining of placental blood, controlled cord traction and uterine massage.
      RELEVANCE TO CLINICAL PRACTICE: There is a need to determine gaps in the clinical
      practices of midwives in regard to the active management of third stage of
      labour, to update knowledge and practices with the latest scientific evidence.

PMID- 23875753
TI  - Synthesis modulation as a tool to increase the catalytic activity of metal
      organic frameworks: the unique case of UiO-66(Zr).
AB  - The catalytic activity of the zirconium terephthalate UiO-66(Zr) can be
      drastically increased by using a modulation approach. The combined use of
      trifluoroacetic acid and HCl during the synthesis results in a highly crystalline
      material, with partial substitution of terephthalates by trifluoroacetate.
      Thermal activation of the material leads not only to dehydroxylation of the
      hexanuclear Zr cluster but also to post-synthetic removal of the trifluoroacetate
      groups, resulting in a more open framework with a large number of open sites.
      Consequently, the material is a highly active catalyst for several Lewis acid
      catalyzed reactions. 

PMID- 23875754
TI  - Role of the central arginine R133 toward the ion selectivity of the phosphate
      specific channel OprP: effects of charge and solvation.
AB  - The outer membrane porin OprP of Pseudomonas aeruginosa forms a highly specific
      phosphate selective channel. This channel is responsible for the high-affinity
      uptake of phosphate ions into the periplasmic space of the bacteria. A detailed
      investigation of the structure-function relationship of OprP is inevitable to
      decipher the anion and phosphate selectivity of this porin in particular and to
      broaden the present understanding of the ion selectivity of different channels.
      To this end we investigated the role of the central arginine of OprP, R133, in
      terms of its effects in selectivity and ion transport properties of the pore.
      Electrophysiological bilayer measurements and free-energy molecular dynamics
      simulations were carried out to probe the transport of different ions through
      various R133 mutants. For these mutants, the change in phosphate binding
      specificity, ion conduction, and anion selectivity was determined and compared to
      previous molecular dynamic calculations and electrophysiological measurements
      with wild-type OprP. Molecular analysis revealed a rather particular role of
      arginine 133 and its charge, while at the same time this residue together with
      the network of other residues, namely, D94 and Y114, has the ability to dehydrate
      the permeating ion. These very specific features govern the ion selectivity of
      OprP. 

PMID- 23875755
TI  - Facility-based review of 296 maternal deaths at a tertiary centre in India: could
      they be prevented?
AB  - AIMS: The aim of this study was to identify causes of maternal mortality at the
      facility and to assess the standard of care, deficiencies in health services and
      preventability of these deaths using facility-based maternal death reviews.
      MATERIAL AND METHODS: This was a prospective study at a tertiary care hospital
      that included all women who died during pregnancy or within 42 days of being
      pregnant during 2005-2010. RESULTS: A review of 296 maternal deaths revealed that
      59% of these occurred in medical wards. Indirect maternal deaths (54%)
      outnumbered the direct deaths (46%). Main causes were hepatitis (18%), hemorrhage
      (10%) and puerperal sepsis (10%). Only 5% of the women had received antenatal
      care at the facility. One-third (34%) were referred from other centers. The
      majority (74%) were critically sick at admission. Most of the women (62%) died
      postpartum. Substandard care and deficient health services were identified in 8%
      and 20% of the cases, respectively. Sixteen (5%) maternal deaths were deemed
      preventable and another 36 (12%) possibly preventable. Since most of the
      preventable deaths (12/16) were due to hemorrhage, measures to control postpartum
      hemorrhage were promoted at the facility. Findings of the maternal death reviews
      were regularly conveyed to the State Health Department for prioritization and
      resource allocation to prevent maternal mortality. CONCLUSION: More maternal
      deaths occurred in the medical than in the obstetrics wards at the facility. The
      leading causes were hepatitis, hemorrhage and puerperal sepsis. Most of the
      deaths were non-preventable as the women were critically sick at admission;
      however, substandard care and health service deficiency were contributory in some
      of the cases.

PMID- 23875756
TI  - Chemical analysis and effect of blueberry and lingonberry fruits and leaves
      against glutamate-mediated excitotoxicity.
AB  - Phenolic compounds are a large class of phytochemicals that are widespread in the
      plant kingdom and known to have antioxidant capacities. This study aimed to
      determine the antioxidant capacities as well as the content of total soluble
      phenolics, anthocyanins, tannins, and flavonoids in the fruits and leaves of
      blueberries and lingonberries growing in Newfoundland. This study also determined
      the potential neuroprotective effect of extracts from fruits and leaves against
      glutamate-mediated excitotoxicity, which is believed to contribute to disorders
      such as stroke and neurodegenerative diseases. Lingonberry and blueberry plants
      were found to be rich sources of phenolic compounds. Total antioxidant capacities
      in terms of radical scavenging activity and reducing power were much higher in
      leaves of both plants as compared to their fruits. These results were in
      correlation with phenolic contents including total flavonoids, anthocyanins, and
      tannins. Brain-derived cell cultures from rats were prepared and grown for about
      2 weeks. Cell cultures were treated with glutamate (100 MUM) for 24 h, and the
      effect of extracts was determined on cells subjected to this excitotoxicity.
      Glutamate treatment caused approximately 23% cell loss when measured after 24 h
      of exposure. Whereas lingonberry fruit extract did not provide protection from
      glutamate toxicity, blueberry fruit extracts were extremely protective. Leaf
      extracts of both lingonberry and blueberry showed a significant neuroprotective
      effect. The greater protective effect of leaf extracts was in correlation with
      the levels of phenolics and antioxidant capacity. These findings suggest that
      berries or their components may contribute to protecting the brain from various
      pathologies.

PMID- 23875757
TI  - BPH/LUTS and ED: common pharmacological pathways for a common treatment.
AB  - INTRODUCTION AND AIM: This article reviews the current literature on common
      physiopathogenetic factors and pharmacological pathways of lower urinary tract
      symptoms (LUTS) and erectile dysfunction (ED) in men and their implications for
      diagnosis and treatment. MAIN OUTCOME MEASURES AND METHODS: A literature search
      was conducted to identify original articles, reviews, editorials, and
      international scientific congress abstracts by combining the following terms:
      lower urinary tract symptoms, erectile dysfunction and phosphodiesterase type 5
      inhibitors (and their abbreviations LUTS, ED and PDE5-Is). RESULTS: We identified
      manuscripts presenting: (i) The existence of several newly discovered common
      pathophysiological mechanisms of LUTS and ED indicating that PDE5-Is might
      represent an alternative to current treatments of men with LUTS (e.g., alpha1
      adrenergic blockers and 5alpha-reductase inhibitors); (ii) Randomized controlled
      clinical trials have shown that treatment with PDE5-Is is associated with
      improvements in both LUTS and ED in men with significant problems in both areas.
      CONCLUSION: The presence of common pathophysiological mechanisms between LUTS and
      ED seems well recognized and needs further exploration. Further comparisons
      between different PDE5-Is would be useful to determine the most appropriate
      regimen and their efficacy to safety ratio.

PMID- 23875760
TI  - Drinking water biofilms on copper and stainless steel exhibit specific molecular
      responses towards different disinfection regimes at waterworks.
AB  - Biofilms growing on copper and stainless steel substrata in natural drinking
      water were investigated. A modular pilot-scale distribution facility was
      installed at four waterworks using different raw waters and disinfection regimes.
      Three-month-old biofilms were analysed using molecular biology and microscopy
      methods. High total cell numbers, low counts of actively respiring cells and low
      numbers of cultivable bacteria indicated the high abundance of viable but not
      cultivable bacteria in the biofilms. The expression of the recA SOS responsive
      gene was detected and underlined the presence of transcriptionally active
      bacteria within the biofilms. This effect was most evident after UV disinfection,
      UV oxidation and UV disinfection with increased turbidity at waterworks compared
      to chemically treated and non-disinfected systems. Furthermore, live/dead
      staining techniques and environmental scanning electron microscopy imaging
      revealed the presence of living and intact bacteria in biofilms on copper
      substrata. Cluster analyses of DGGE profiles demonstrated differences in the
      composition of biofilms on copper and steel materials. 

PMID- 23875758
TI  - Gene bionetworks that regulate ovarian primordial follicle assembly.
AB  - BACKGROUND: Primordial follicle assembly is the process by which ovarian
      primordial follicles are formed. During follicle assembly oocyte nests break down
      and a layer of pre-granulosa cells surrounds individual oocytes to form
      primordial follicles. The pool of primordial follicles formed is the source of
      oocytes for ovulation during a female's reproductive life. RESULTS: The current
      study utilized a systems approach to detect all genes that are differentially
      expressed in response to seven different growth factor and hormone treatments
      known to influence (increase or decrease) primordial follicle assembly in a
      neonatal rat ovary culture system. One novel factor, basic fibroblast growth
      factor (FGF2), was experimentally determined to inhibit follicle assembly. The
      different growth factor and hormone treatments were all found to affect similar
      physiological pathways, but each treatment affected a unique set of
      differentially expressed genes (signature gene set). A gene bionetwork analysis
      identified gene modules of coordinately expressed interconnected genes and it was
      found that different gene modules appear to accomplish distinct tasks during
      primordial follicle assembly. Predictions of physiological pathways important to
      follicle assembly were validated using ovary culture experiments in which ERK1/2
      (MAPK1) activity was increased. CONCLUSIONS: A number of the highly
      interconnected genes in these gene networks have previously been linked to
      primary ovarian insufficiency (POI) and polycystic ovarian disease syndrome
      (PCOS). Observations have identified novel factors and gene networks that
      regulate primordial follicle assembly. This systems biology approach has helped
      elucidate the molecular control of primordial follicle assembly and provided
      potential therapeutic targets for the treatment of ovarian disease.

PMID- 23875761
TI  - 3Omics: a web-based systems biology tool for analysis, integration and
      visualization of human transcriptomic, proteomic and metabolomic data.
AB  - BACKGROUND: Integrative and comparative analyses of multiple transcriptomics,
      proteomics and metabolomics datasets require an intensive knowledge of tools and
      background concepts. Thus, it is challenging for users to perform such analyses,
      highlighting the need for a single tool for such purposes. The 3Omics one-click
      web tool was developed to visualize and rapidly integrate multiple human inter-
      or intra-transcriptomic, proteomic, and metabolomic data by combining five
      commonly used analyses: correlation networking, coexpression, phenotyping,
      pathway enrichment, and GO (Gene Ontology) enrichment. RESULTS: 3Omics generates
      inter-omic correlation networks to visualize relationships in data with respect
      to time or experimental conditions for all transcripts, proteins and metabolites.
      If only two of three omics datasets are input, then 3Omics supplements the
      missing transcript, protein or metabolite information related to the input data
      by text-mining the PubMed database. 3Omics' coexpression analysis assists in
      revealing functions shared among different omics datasets. 3Omics' phenotype
      analysis integrates Online Mendelian Inheritance in Man with available transcript
      or protein data. Pathway enrichment analysis on metabolomics data by 3Omics
      reveals enriched pathways in the KEGG/HumanCyc database. 3Omics performs
      statistical Gene Ontology-based functional enrichment analyses to display
      significantly overrepresented GO terms in transcriptomic experiments. Although
      the principal application of 3Omics is the integration of multiple omics
      datasets, it is also capable of analyzing individual omics datasets. The
      information obtained from the analyses of 3Omics in Case Studies 1 and 2 are also
      in accordance with comprehensive findings in the literature. CONCLUSIONS: 3Omics
      incorporates the advantages and functionality of existing software into a single
      platform, thereby simplifying data analysis and enabling the user to perform a
      one-click integrated analysis. Visualization and analysis results are
      downloadable for further user customization and analysis. The 3Omics software can
      be freely accessed at http://3omics.cmdm.tw.

PMID- 23875762
TI  - A cross sectional survey of attitudes, awareness and uptake of the parental
      pertussis booster vaccine as part of a cocooning strategy, Victoria, Australia.
AB  - BACKGROUND: The Victorian Government Department of Health funded a diphtheria,
      tetanus and acellular pertussis vaccine for parents of infants from June 2009 to
      June 2012 as part of a cocooning strategy for the control of pertussis. The aim
      of this study was to assess parents' attitudes and awareness of the vaccination
      program, and to estimate vaccine uptake. METHODS: A cross-sectional survey of 253
      families with a child born in the first quarter of 2010 residing within five
      metropolitan and four rural local government areas in Victoria was conducted.
      Univariate analyses were performed to describe the relationship between
      demographic variables, knowledge and awareness of the disease, the vaccine
      program and vaccine uptake. Multivariate analyses examining predictors for
      awareness of the vaccine program and for the uptake of vaccination were also
      conducted. RESULTS: One hundred and five families were surveyed (response rate
      43%). Of these, 93% indicated that they had heard of 'pertussis' or 'whooping
      cough' and 75% of mothers and 69% of fathers were aware the pertussis vaccine was
      available and funded for new parents. Overall, 70% of mothers and 53% of fathers
      were vaccinated following their child's birth, with metropolitan fathers less
      likely to be vaccinated as rural fathers (RR=0.6, p=0.002). Being a younger
      mother (p=0.02) or father (p=0.047), and being an Australian-born father (RR=1.9,
      p=0.03) were found to predict uptake of the vaccine in parents. CONCLUSION:
      Parents indicated a reasonable level of knowledge of pertussis and a willingness
      to be vaccinated to protect their child. However, vaccine uptake estimates
      indicated further opportunity for program improvement. Future cocooning
      strategies would benefit from specifically targeting fathers and metropolitan
      maternity hospitals to increase vaccine uptake. Wider promotion of the
      availability of vaccine providers may increase uptake to maximise the success of
      cocooning programs. Further investigation of the effectiveness of the cocooning
      strategy in decreasing infant morbidity and mortality is required.

PMID- 23875763
TI  - Hepatotoxicity: a scheme for generating chemical categories for read-across,
      structural alerts and insights into mechanism(s) of action.
AB  - The ability of a compound to cause adverse effects to the liver is one of the
      most common reasons for drug development failures and the withdrawal of drugs
      from the market. Such adverse effects can vary tremendously in severity, leading
      to an array of possible drug-induced liver injuries (DILIs). As a result, it is
      not surprising that drug development has evolved into a complex and multifaceted
      process including methods aiming to identify potential liver toxicities.
      Unfortunately, hepatotoxicity remains one of the most complex and poorly
      understood areas of human toxicity; thus it is a significant challenge to
      identify potential hepatotoxins. The performance of existing methods to identify
      hepatotoxicity requires improvement. The current study details a scheme for
      generating chemical categories and the development of structural alerts able to
      identify potential hepatotoxins. The study utilized a diverse 951-compound
      dataset and used structural similarity methods to produce a number of
      structurally restricted categories. From these categories, 16 structural alerts
      associated with observed human hepatotoxicity were developed. Furthermore, the
      mechanism(s) by which these compounds cause hepatotoxicity were investigated and
      a mechanistic rationale was proposed, where possible, to yield mechanistically
      supported structural alerts. Alerts of this nature have the potential to be used
      in the screening of compounds to highlight potential hepatotoxicity, whilst the
      chemical categories themselves are important in applying read-across approaches.
      The scheme presented in this study also has the potential to act as a knowledge
      generator serving as an excellent starting platform from which to conduct
      additional toxicological studies.

PMID- 23875764
TI  - Sesquiterpene lactones: adverse health effects and toxicity mechanisms.
AB  - Sesquiterpene lactones (STLs) present a wide range of biological activities,
      mostly based on their alkylating capabilities, which underlie their therapeutic
      potential. These compounds are the active constituents of a variety of plants,
      frequently used as herbal remedies. STLs such as artemisinin and its derivatives
      are in use as first-line antimalarials while others, such as parthenolide, have
      recently reached cancer clinical trials. However, the toxicological profile of
      these compounds must be thoroughly characterized, since the same properties that
      make STL useful medicines can also cause severe toxicity. STL-containing plants
      have long been known to induce a contact dermatitis in exposed farm workers, and
      also to cause several toxic syndromes in farm animals. More recently, concerns
      are been raised regarding the genotoxic potential of these compounds and the
      embryotoxicity of artemisinins. A growing number of STLs are being reported to be
      mutagenic in different in vitro and in vivo assays. As yet no systematic studies
      have been published, but the genotoxicity of STLs seems to depend not so much on
      direct DNA alkylation as on oxidative DNA damage and other partially elucidated
      mechanisms. As the medicinal use of these compounds increases, further studies of
      their toxic potential are needed, especially those focusing on the structural
      determinants of genotoxicity and embryotoxicity.

PMID- 23875765
TI  - Hormetic mechanisms.
AB  - This article provides the first extensive documentation of mechanisms of hormetic
      dose/concentration responses. The mechanisms selected were principally those
      mediated via receptor and/or cell signaling pathways. Mechanisms are reported for
      greater than 100 agents affecting nearly 400 dose/concentration responses from a
      wide range of chemical classes, affecting a broad range of cell types and
      endpoints. Regardless of the model (i.e. in vitro or in vivo), inducing agent,
      endpoint, or receptor/cell signaling pathway mediated mechanism, the quantitative
      features of the hormetic dose/concentration responses are similar, suggesting
      that the magnitude of the response is a measure of biological plasticity, within
      a broad range of biological contexts. These findings represent an important
      advance in the understanding of the hormetic dose/concentration response, its
      generalizability and potential biomedical applications, including drug
      discovery/efficacy assessment and the risk assessment process.

PMID- 23875766
TI  - Relationship between urinary sodium excretion and serum aldosterone in patients
      with diabetes in the presence and absence of modifiers of the renin-angiotensin
      aldosterone system.
AB  - Although low dietary salt intake has beneficial effects on BP (blood pressure),
      low 24hUNa (24 h urinary sodium excretion), the most accurate estimate of dietary
      salt intake, is associated with increased mortality in people with diabetes. In
      the non-diabetic population, low salt intake is associated with increased RAAS
      (renin-angiotensin-aldosterone system) activity. In this cross-sectional study,
      we examined the relationship between 24hUNa, PRA (plasma renin activity), serum
      aldosterone and BNP (brain natriuretic peptide) in patients with diabetes.
      Clinical characteristics, 24hUNa, PRA, serum aldosterone and BNP were recorded in
      222 consecutive patients (77% with Type 2 diabetes) attending a diabetes clinic
      at a tertiary hospital. The relationship between 24hUNa, serum aldosterone, PRA,
      BNP, urinary potassium excretion, serum potassium, serum sodium, eGFR (estimated
      glomerular filtration rate), urinary albumin excretion and HbA1c (glycated
      haemoglobin) was examined by a multivariable regression model. Levels of 24hUNa
      significantly predicted serum aldosterone in a linear fashion (R2=0.20, P=0.002).
      In the subgroup of patients (n=46) not taking RAAS-modifying agents, this
      relationship was also observed (R2=0.10, P=0.03), and the effect of 24hUNa on
      serum aldosterone was found to be more pronounced than in the whole cohort
      (coefficient=-0.0014, compared with -0.0008). There was no demonstrable
      relationship between 24hUNa and PRA or BNP. Low 24hUNa is associated with
      increased serum aldosterone in people with diabetes, in the presence and absence
      of RAAS-modifying agents. This raises the possibility that stimulation of the
      RAAS may be a mechanism that contributes to adverse outcomes observed in patients
      with low 24hUNa.

PMID- 23875767
TI  - Airway management in pierre robin sequence: patterns of practice.
AB  - Objectives : To report survey results from American Cleft Palate-Craniofacial
      Association members on the practice patterns of airway obstruction management in
      patients with Pierre Robin sequence. Design : A 10-question online survey was
      sent and the data were reviewed. Setting : Online survey of members of the
      American Cleft Palate-Craniofacial Association. Patients : Surveys assessed
      management patterns of patients with Pierre Robin sequence whom a surgeon member
      of the American Cleft Palate-Craniofacial Association treated for airway
      obstruction. Interventions : The survey comprised data on management strategies
      for airway obstruction in Pierre Robin sequence, including tracheostomy, tongue
      lip adhesion, mandibular distraction, and treatments that falls in the "other"
      category. Results : A total of 87 American Cleft Palate-Craniofacial Association
      members completed the survey. Respondents' results were analyzed as a whole and
      by individual subspecialty: plastic surgery (n = 33), oromaxillofacial surgery (n
      = 21), and otolaryngology (n = 29). Although most of the surgeons were trained to
      manage airway obstruction in Pierre Robin sequence patients using tracheostomy
      (47%, n = 39) and tongue-lip adhesion (31%, n = 26), 48% reported a current
      preference for mandibular distraction (n = 40). Of surgeons who preferred to
      manage Pierre Robin sequence with tongue-lip adhesion (n = 23), 65% were trained
      to do so (n = 15). Surgeons preferring mandibular distraction (n = 40) and
      tracheostomy (n = 14) more often reported they were trained to manage Pierre
      Robin sequence with tracheostomy. Conclusions : Currently there are various
      practice patterns for the management of airway obstruction in Pierre Robin
      sequence. Training habits and subspecialty category may influence a surgeon's
      preference in patients who fail conservative therapy. Treatment guidelines are
      lacking and may require significant collaboration among centers and
      subspecialties to develop a more standardized approach to a challenging clinical
      entity. 

PMID- 23875768
TI  - To the editor:.

PMID- 23875769
TI  - Spontaneous transition of wide QRS tachycardia: what is the mechanism?

PMID- 23875770
TI  - Six-decade change in water chemistry of large freshwater Lake Taihu, China.
AB  - Taihu lake has become a hot spot internationally due to its algae bloom. However,
      its natural water chemistry (major ions) received little attention though it is
      equally important for drinking water and aquatic ecology. Using historical data
      (1950s-2012) we explored the drastic change of Taihu water chemistry over the
      past six decades and the driving factors. Results show that major ions increased
      around 2-7-fold and TDS increased nearly 3-fold during the last 60 years. The
      dominant cation has shifted from Ca(2+) to Na(+), and the current Cl(-) is
      dominant over HCO3(-), the predominant anion before the 2000s. Analyses show that
      population increase and human activities were the major driving factors
      responsible for the drastic change. Whereas the mechanism of increase was
      different for ions, i.e., Na(+) and Cl(-) increase was directly related to the
      population increase and sewage discharge in the basin; SO4(2-) was related to
      atmospheric deposition derived from increasing coal consumption and SO2
      emissions; hardness (Ca and Mg) increase was closely linked to the acidic
      precipitation. No increase trend of HCO3(-) was attributable to frequent
      outbreaks of algae bloom which consumed HCO3(-). Estimation indicated that sewage
      discharge in the basin contributed 23% to the lake in terms of Cl(-), exceeding
      the contribution from rock weathering. Current water chemistry of Taihu lake has
      become "anthropogenic dominance" from its original rock dominance. 

PMID- 23875771
TI  - Markers of coagulation activation, endothelial stimulation, and inflammation in
      dogs with babesiosis.
AB  - BACKGROUND: Babesia infections in dogs can result in a wide range of clinical and
      laboratory presentations, including coagulopathy. Expression of intercellular
      adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF) in dogs with
      babesiosis is unknown. OBJECTIVES: Whether inflammation in babesiosis triggers
      activation of ICAM-1 and the coagulation system. ANIMALS: Twelve and 10 dogs with
      naturally occurring babesiosis before and after antiparasitic treatment,
      respectively, were compared with 10 healthy dogs. METHODS: In this prospective
      study, diagnosis was made by blood smear examination and confirmed by PCR. C
      reactive protein (CRP), soluble intercellular adhesion molecule 1 (sICAM-1), and
      von Willebrand factor (vWF) levels were measured by a canine ELISA kit,
      fibrinogen (FIB) and factor VIII activity levels were measured by coagulometric
      methods, and blood cell counts (WBC, RBC, PLT) were determined with an automatic
      analyzer. RESULTS: Compared to healthy dogs, the CRP, sICAM-1, and FIB
      concentrations were significantly increased before therapy and remained high for
      3 days after therapy in dogs with babesiosis. vWF activity was significantly
      decreased in dogs with babesiosis before treatment. FVIII activity did not differ
      between dogs with babesiosis and healthy dogs. WBC; RBC and PLT were
      significantly lower before treatment and normalized by 3 days after treatment.
      CONCLUSION AND CLINICAL IMPORTANCE: A proinflammatory condition in babesiosis
      appears to influence endothelial dysfunction and hemostatic activity. Although
      clearly beneficial for the parasite, sequestered blood cells can obstruct blood
      flow in small vessels, promote an inflammatory state, and could increase the
      severity of babesiosis.

PMID- 23875772
TI  - Direct measurements of mass-specific optical cross sections of single-component
      aerosol mixtures.
AB  - The optical properties of atmospheric aerosols vary widely, being dependent upon
      particle composition, morphology, and mixing state. This diversity and complexity
      of aerosols motivates measurement techniques that can discriminate and quantify a
      variety of single- and multicomponent aerosols that are both internally and
      externally mixed. Here, we present a new combination of techniques to directly
      measure the mass-specific extinction and absorption cross sections of laboratory
      generated aerosols that are relevant to atmospheric studies. Our approach employs
      a tandem differential mobility analyzer, an aerosol particle mass analyzer,
      cavity ring-down and photoacoustic spectrometers, and a condensation particle
      counter. This suite of instruments enables measurement of aerosol particle size,
      mass, extinction and absorption coefficients, and aerosol number density,
      respectively. Taken together, these observables yield the mass-specific
      extinction and absorption cross sections without the need to model particle
      morphology or account for sample collection artifacts. Here we demonstrate the
      technique in a set of case studies which involve complete separation of aerosol
      by charge, separation of an external mixture by mass, and discrimination between
      particle types by effective density and single-scattering albedo. 

PMID- 23875774
TI  - Influence of Off-resonance in myocardial T1-mapping using SSFP based MOLLI
      method.
AB  - BACKGROUND: Myocardial T1-mapping methods such as MOLLI use SSFP readout and are
      prone to frequency-dependent error in T1-measurement. A significant error in T1
      may result at relatively small off-resonance frequencies that are well within the
      region without banding artifacts. METHODS: The sensitivity of T1-estimates based
      on the SSFP based MOLLI sequence to errors in center frequency are calculated by
      means of a Bloch simulation and validated by phantom measurements. Typical off
      resonance errors following local cardiac shimming are determined by field mapping
      at both 1.5 and 3.0T. In vivo examples demonstrate the artifactual appearance of
      T1-maps in the presence of off-resonance variation. RESULTS: Off-resonance varied
      61.8 +/- 15.5 Hz (mean +/- SD, n = 18) across the heart at 1.5T and 125.0 +/-
      40.6 Hz (mean +/- SD, n = 18) at 3.0T. For T1 = 1000 ms, the variation in T1 due
      to off-resonance variation was approximately 20 ms at 62 Hz, and > 50 ms at 125
      Hz. CONCLUSIONS: Regional variations due to the inability to completely shim the
      B0-field variation around the heart appear as regional variation in T1, which is
      artifactual.

PMID- 23875773
TI  - The tachykinin peptide neurokinin B binds copper forming an unusual [CuII(NKB)2]
      complex and inhibits copper uptake into 1321N1 astrocytoma cells.
AB  - Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides that
      have neuroinflammatory, neuroimmunological, and neuroprotective functions. In a
      neuroprotective role, tachykinins can help protect cells against the neurotoxic
      processes observed in Alzheimer's disease. A change in copper homeostasis is a
      clear feature of Alzheimer's disease, and the dysregulation may be a contributory
      factor in toxicity. Copper has recently been shown to interact with neurokinin A
      and neuropeptide gamma and can lead to generation of reactive oxygen species and
      peptide degradation, which suggests that copper may have a place in tachykinin
      function and potentially misfunction. To explore this, we have utilized a range
      of spectroscopic techniques to show that NKB, but not substance P, can bind
      Cu(II) in an unusual [Cu(II)(NKB)2] neutral complex that utilizes two N-terminal
      amine and two imidazole nitrogen ligands (from each molecule of NKB) and the
      binding substantially alters the structure of the peptide. Using 1321N1
      astrocytoma cells, we show that copper can enter the cells and subsequently open
      plasma membrane calcium channels but when bound to neurokinin B copper ion uptake
      is inhibited. This data suggests a novel role for neurokinin B in protecting
      cells against copper-induced calcium changes and implicates the peptide in
      synaptic copper homeostasis. 

PMID- 23875775
TI  - Neonatal orbital abscess after sinus surgery: case report and brief review.
AB  - Orbital abscess formation in neonates is rare, with only 12 cases reported in the
      literature. We present a case of orbital cellulitis with orbital abscesses
      following repair of congenital choanal atresia in a 2-week-old neonate. This is
      the first reported case of an orbital abscess following a sinus procedure in a
      neonate.

PMID- 23875776
TI  - The crosstalk between Nrf2 and AMPK signal pathways is important for the anti
      inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin
      shocked mice.
AB  - AIMS: The response of AMP-activated protein kinase (AMPK) to oxidative stress has
      been recently reported but the downstream signals of this response are largely
      unknown. Meanwhile, the upstream events for the activation of nuclear factor
      erythroid-2-related factor-2 (Nrf2), a critical transcriptional activator for
      antioxidative responses, remain unclear. In the present study, we investigated
      the relationship between AMPK and Nrf2 signal pathways in lipopolysaccharide
      (LPS)-triggered inflammatory system, in which berberine (BBR), a known AMPK
      activator, was used for inflammation suppression. RESULTS AND INNOVATION: In
      inflammatory macrophages, BBR attenuated LPS-induced expression of inflammatory
      genes (inducible nitric oxide synthase [iNOS], cyclooxygenase-2 [COX2],
      interleukin [IL]-6), and the generation of nitric oxide and reactive oxygen
      species, but increased the transcription of Nrf2-targeted antioxidative genes
      (NADPH quinone oxidoreductase-1 [NQO-1], heme oxygenase-1 [HO-1]), as well as the
      nuclear localization and phosphorylation of Nrf2 protein. Importantly, we found
      BBR-induced activation of Nrf2 is AMPK-dependent, as either pharmacologically or
      genetically inactivating AMPK blocked the activation of Nrf2. Consistent with in
      vitro experiments, BBR down-regulated the expression of proinflammatory genes but
      upregulated those of Nrf2-targeted genes in lungs of LPS-injected mice, and these
      effects were attenuated in Nrf2-deficient mice. Moreover, the effect of BBR on
      survival time extension and plasma redox regulation in endotoxin-shocked mice was
      largely weakened when Nrf2-depleted. CONCLUSIONS: Our results demonstrate
      convergence between AMPK and Nrf2 pathways and this intersection is essential for
      anti-inflammatory effect of BBR in LPS-stimulated macrophages and endotoxin
      shocked mice. Uncovering this intersection is significant for understanding the
      relationship between energy homeostasis and antioxidative responses and may be
      beneficial for developing new therapeutic strategies against inflammatory
      diseases. Antioxid. Redox Signal. 20, 574-588.

PMID- 23875777
TI  - Synaptodendritic recovery following HIV Tat exposure: neurorestoration by
      phytoestrogens.
AB  - HIV-1 infects the brain and, despite antiretroviral therapy, many infected
      individuals suffer from HIV-1-associated neurocognitive disorders (HAND). HAND is
      associated with dendritic simplification and synaptic loss. Prevention of
      synaptodendritic damage may ameliorate or forestall neurocognitive decline in
      latent HIV-1 infections. The HIV-1 transactivating protein (Tat) is produced
      during viral latency in the brain and may cause synaptodendritic damage. This
      study examined the integrity of the dendritic network after exposure to HIV-1 Tat
      by labeling filamentous actin (F-actin)-rich structures (puncta) in primary
      neuronal cultures. After 24 h of treatment, HIV-1 Tat was associated with the
      dendritic arbor and produced a significant reduction of F-actin-labeled dendritic
      puncta as well as loss of dendrites. Pre-treatment with either of two plant
      derived phytoestrogen compounds (daidzein and liquiritigenin), significantly
      reduced synaptodendritic damage following HIV-1 Tat treatment. In addition, 6
      days after HIV-1 Tat treatment, treatment with either daidzein, or liquiritigenin
      enhanced recovery, via the estrogen receptor, from HIV-1 Tat-induced
      synaptodendritic damage. These results suggest that either liquiritigenin or
      daidzein may not only attenuate acute synaptodendritic injury in HIV-1 but may
      also promote recovery from synaptodendritic damage. The HIV-1 transactivating
      protein (Tat) is produced during viral latency in the brain. Treatment with
      either daidzein or liquiritigenin restored the loss of synaptic connectivity
      produced by HIV-1 Tat. This neurorestoration was mediated by estrogen receptors
      (ER). These results suggest that plant-derived phytoestrogens may promote
      recovery from HIV-1-induced synaptodendritic damage.

PMID- 23875778
TI  - Pediatric lipidology.

PMID- 23875779
TI  - Depending on the stage of hepatosteatosis, p53 causes apoptosis primarily through
      either DRAM-induced autophagy or BAX.
AB  - BACKGROUND & AIMS: Apoptosis mediated by p53 plays a pathological role in the
      progression of hepatosteatosis. It is noteworthy that p53 can promote the
      expression of damage-regulated autophagy modulator (DRAM), an inducer of
      autophagy-mediated apoptosis. However, the relationship between p53-mediated
      apoptosis and autophagy in hepatosteatosis remains elusive. This study aimed to
      examine how p53 orchestrates autophagy and apoptosis to affect hepatosteatosis.
      METHODS: HepG2 cells were treated with oleic acid (OA) for 24 h to induce
      hepatosteatosis. Mice were fed a high-fat diet for 20 or 40 weeks to induce
      hepatosteatosis. RESULTS: OA induced a dose-dependent increase in steatosis
      severity and apoptosis. OA also induced autophagy, which was a critical inducer
      of apoptosis in mild steatosis induced by 400 MUM OA, but not in the more severe
      steatosis induced by 800 and 1200 MUM OA. p53 inhibition by siRNA mostly blocked
      OA-induced apoptosis and autophagy. Moreover, OA-induced autophagy was DRAM
      dependent and primarily occurred in the mitochondria (mitophagy), where DRAM was
      localized. In severe steatosis induced by 1200 MUM OA, apoptosis was mainly
      dependent on p53-induced expression of BAX, which was also localized to the
      mitochondria. Our in vivo study showed that p53 expression increased in both mild
      and severe hepatosteatosis. Increased DRAM expression and autophagy were
      identified in mild hepatosteatosis, whereas greater BAX expression was observed
      in severe hepatosteatosis. CONCLUSIONS: p53 may induce apoptosis via different
      mechanisms. DRAM-mediated mitophagy is a primary apoptotic inducer in mild
      hepatosteatosis, whereas p53-induced BAX expression mainly induces apoptosis in
      severe hepatosteatosis.

PMID- 23875780
TI  - Electrospray formation of gelled nano-aluminum microspheres with superior
      reactivity.
AB  - Nanometallic fuels with high combustion enthalpy, such as aluminum, have been
      proposed as a potential fuel replacement for conventional metallic fuel to
      improve propellant performance in a variety of propulsive systems. Nevertheless,
      nanometallic fuels suffer from the processing challenges in polymer formulations
      such as increased viscosity and large agglomeration, which hinder their
      implementation. In this letter, we employ electrospray as a means to create a gel
      within a droplet, via a rapid, solvent evaporation-induced aggregation of
      aluminum nanoparticles, containing a small mass fraction of an energetic binder.
      The gelled aluminum microspheres were characterized and tested for their burning
      behavior by rapid wire heating ignition experiments. The gelled aluminum
      microspheres show enhanced combustion behavior compared to nanoaluminum, which
      possibly benefits from the nitrocellulose coating and the gelled microstructure,
      and is far superior to the corresponding dense micrometer-sized aluminum. 

PMID- 23875781
TI  - Influence of pH on the reductive transformation of birnessite by aqueous Mn(II).
AB  - We investigated the effect of pH (5.5-8.5) on the mineralogical transformation of
      hexagonal birnessite induced by reaction with aqueous Mn(II) (50-2200 MUM), using
      batch sorption experiments, X-ray diffraction analyses, X-ray absorption and
      infrared spectroscopic measurements. Samples reacted at pH < 7.0 exhibited
      disrupted stacking of birnessite sheets, but no mineralogical transformation
      products were observed. At pH 7.0 and 7.5, reaction with Mn(II) under anoxic
      conditions caused reductive transformation of birnessite into manganite (gamma
      MnOOH), whereas at pH 8.0 and 8.5, conversion into hausmannite (Mn3O4) occurred.
      Feitknechtite (beta-MnOOH) is a major transformation product at low Mn(II) inputs
      at pH 7.0-8.5, and represents a metastable reaction intermediate that is
      converted into manganite and possibly hausmannite during further reaction with
      Mn(II). Thermodynamic calculations suggest that conversion into hausmannite at
      alkaline pH reflects a kinetic effect where rapid hausmannite precipitation
      prevents formation of thermodynamically more favorable manganite. In oxic
      systems, feitknechtite formation due to surface catalyzed oxidation of Mn(II) by
      O2 increases Mn(II) removal relative to anoxic systems at pH >= 7. The results of
      this study suggest that aqueous Mn(II) is an important control on the mineralogy
      and reactivity of natural Mn-oxides, particularly in aqueous geochemical
      environments with neutral to alkaline pH values. 

PMID- 23875782
TI  - Investigation of the geographical scale of adaptive phenological variation and
      its underlying genetics in Arabidopsis thaliana.
AB  - Despite the increasing number of genomic tools, identifying the genetics
      underlying adaptive complex traits remains challenging in the model species
      Arabidopsis thaliana. This is due, at least in part, to the lack of data on the
      geographical scale of adaptive phenotypic variation. The aims of this study were
      (i) to tease apart the historical roles of adaptive and nonselective processes in
      shaping phenological variation in A. thaliana in France and (ii) to gain insights
      into the spatial scale of adaptive variation by identifying the putative
      selective agents responsible for this selection. Forty-nine natural stands from
      four climatically contrasted French regions were characterized (i) phenologically
      for six traits, (ii) genetically using 135 SNP markers and (iii) ecologically for
      42 variables. Up to 63% of phenological variation could be explained by neutral
      genetic diversity. The remaining phenological variation displayed stronger
      associations with ecological variation within regions than among regions,
      suggesting the importance of local selective agents in shaping adaptive
      phenological variation. Although climatic conditions have often been suggested as
      the main selective agents acting on phenology in A. thaliana, both edaphic
      conditions and interspecific competition appear to be strong selective agents in
      some regions. In a first attempt to identify the genetics of phenological
      variation at different geographical scales, we phenotyped worldwide accessions
      and local polymorphic populations from the French RegMap in a genome-wide
      association (GWA) mapping study. The genomic regions associated with phenological
      variation depended upon the geographical scale considered, stressing the need to
      account for the scale of adaptive phenotypic variation when choosing accession
      panels for GWAS. 

PMID- 23875783
TI  - Role of adiponectin and its receptor in prediction of reproductive outcome of
      metformin treatment in patients with polycystic ovarian syndrome.
AB  - AIMS: The aim of this study was to examine the effect of metformin on serum
      adiponectin and adiponectin receptor-1 (AdipoR1) and evaluate their role in
      prediction of ovulation in patients with polycystic ovarian syndrome (PCOS).
      MATERIAL AND METHODS: The study cohort included 68 PCOS patients with clomiphene
      citrate resistance (group 1) and 28 healthy women as controls (group 2). Baseline
      serum adiponectin, AdipoR1, total testosterone (T), and homeostasis model of
      insulin resistance (HOMA-IR) were measured in all participants. Group 1 received
      metformin (1500 mg/day) for 6 months followed by second blood sampling. RESULTS:
      Group 1 had significantly lower baseline adiponectin and AdipoR1 (P = 0.001)
      compared to group 2. During treatment, metformin resulted in conception in 5/68
      (7%), ovulation in 33/68 (48%) and regular cycles in 41/68 (60%) patients. Group
      1 showed post-metformin higher adiponectin and AdipoR1 (P = 0.01) and lower HOMA
      IR (P = 0.006) and T (P = 0.001) compared to pre-treatment levels. Post-metformin
      ovulatory patients had higher adiponectin and AdipoR1 and lower HOMA-IR and T
      compared to anovulatory patients. Multivariate regression analysis in group 1
      showed that only T and HOMA-IR were significant independent factors for
      predicting ovulatory cycles during metformin treatment (P = 0.04 and P = 0.05,
      respectively). CONCLUSIONS: Metformin treatment enhances both adiponectin
      activity and insulin sensitivity, resulting in a less hyperandrogenic state in
      patients with PCOS. Serum adiponectin and AdipoR1 are poor predictors of
      ovulatory outcome during treatment.

PMID- 23875784
TI  - Modeling heterogeneous responsiveness of intrinsic apoptosis pathway.
AB  - BACKGROUND: Apoptosis is a cell suicide mechanism that enables multicellular
      organisms to maintain homeostasis and to eliminate individual cells that threaten
      the organism's survival. Dependent on the type of stimulus, apoptosis can be
      propagated by extrinsic pathway or intrinsic pathway. The comprehensive
      understanding of the molecular mechanism of apoptotic signaling allows for
      development of mathematical models, aiming to elucidate dynamical and systems
      properties of apoptotic signaling networks. There have been extensive efforts in
      modeling deterministic apoptosis network accounting for average behavior of a
      population of cells. Cellular networks, however, are inherently stochastic and
      significant cell-to-cell variability in apoptosis response has been observed at
      single cell level. RESULTS: To address the inevitable randomness in the intrinsic
      apoptosis mechanism, we develop a theoretical and computational modeling
      framework of intrinsic apoptosis pathway at single-cell level, accounting for
      both deterministic and stochastic behavior. Our deterministic model, adapted from
      the well-accepted Fussenegger model, shows that an additional positive feedback
      between the executioner caspase and the initiator caspase plays a fundamental
      role in yielding the desired property of bistability. We then examine the impact
      of intrinsic fluctuations of biochemical reactions, viewed as intrinsic noise,
      and natural variation of protein concentrations, viewed as extrinsic noise, on
      behavior of the intrinsic apoptosis network. Histograms of the steady-state
      output at varying input levels show that the intrinsic noise could elicit a wider
      region of bistability over that of the deterministic model. However, the system
      stochasticity due to intrinsic fluctuations, such as the noise of steady-state
      response and the randomness of response delay, shows that the intrinsic noise in
      general is insufficient to produce significant cell-to-cell variations at
      physiologically relevant level of molecular numbers. Furthermore, the extrinsic
      noise represented by random variations of two key apoptotic proteins, namely
      Cytochrome C and inhibitor of apoptosis proteins (IAP), is modeled separately or
      in combination with intrinsic noise. The resultant stochasticity in the timing of
      intrinsic apoptosis response shows that the fluctuating protein variations can
      induce cell-to-cell stochastic variability at a quantitative level agreeing with
      experiments. Finally, simulations illustrate that the mean abundance of
      fluctuating IAP protein is positively correlated with the degree of cellular
      stochasticity of the intrinsic apoptosis pathway. CONCLUSIONS: Our theoretical
      and computational study shows that the pronounced non-genetic heterogeneity in
      intrinsic apoptosis responses among individual cells plausibly arises from
      extrinsic rather than intrinsic origin of fluctuations. In addition, it predicts
      that the IAP protein could serve as a potential therapeutic target for
      suppression of the cell-to-cell variation in the intrinsic apoptosis
      responsiveness.

PMID- 23875786
TI  - Double jeopardy: Blepharophimosis syndrome with congenital nasolacrimal duct
      obstruction in twins.
AB  - PURPOSE: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an
      autosomal dominant disorder characterized by bilateral ptosis with poor levator
      function, epicanthus inversus and shortened horizontal palpebral fissures.
      METHOD: Eighteen -month -old twin sisters presented with history of watering from
      their left eyes since birth. Examination revealed features of BPES with left
      congenital nasolacrimal duct obstruction in both. RESULT: the twins underwent
      therapeutic probing, which was successful in one and failed in the other. the
      second child was subsequently managed by external dacryocystorhinostomy.
      CONCLUSION: To our knowledge, this is the first report of Blepharophimosis
      syndrome with congenital nasolacrimal duct obstruction occurring in twin sisters.

PMID- 23875785
TI  - Structural insights into fibrinogen dynamics using amide hydrogen/deuterium
      exchange mass spectrometry.
AB  - We determined the amide hydrogen/deuterium exchange profile of native human
      fibrinogen under physiologic conditions. After optimization of the quench and
      proteolysis conditions, more than 1,200 peptides were identified by mass
      spectrometry, spanning more than 90% of the constituent Aalpha, Bbeta, and gamma
      chain amino acid sequences. The compact central and distal globular regions of
      fibrinogen were well protected from deuterium exchange, with the exception of the
      unfolded amino-terminal segments of the Aalpha and Bbeta chains extending from
      the central region, and the short gamma chain "tail" extending from each distal
      globular region. The triple-helical coiled-coil regions, which bridge the central
      region to each distal region, were also well protected with the exception of a
      moderately fast-exchanging area in the middle of each coiled-coil adjacent to the
      gamma chain carbohydrate attachment site. These dynamic regions appear to provide
      flexibility to the fibrinogen molecule. The gamma chain "out loop" contained
      within each coiled-coil also exchanged rapidly. The alphaC domain (Aalpha 392
      610) exchanged rapidly, with the exception of a short segment sandwiched between
      a conserved disulfide linkage in the N-terminal alphaC subdomain. This latter
      finding is consistent with a mostly disordered structure for the alphaC domain in
      native fibrinogen. Analysis of the dysfibrinogen Bbeta 235 Pro/Leu, which
      exhibits abnormal fibrin structure, revealed enhanced deuterium exchange
      surrounding the Pro/Leu substitution site as well as in the vicinity of the high
      affinity calcium binding site and the A knob polymerization pocket within the
      gammaC domain. The implication of these changes with respect to fibrin structure
      is discussed. 

PMID- 23875787
TI  - Stimuli-responsive bacterial cellulose-g-poly(acrylic acid-co-acrylamide)
      hydrogels for oral controlled release drug delivery.
AB  - This study evaluated the potential of stimuli-responsive bacterial cellulose-g
      poly(acrylic acid-co-acrylamide) hydrogels as oral controlled-release drug
      delivery carriers. Hydrogels were synthesized by graft copolymerization of the
      monomers onto bacterial cellulose (BC) fibers by using a microwave irradiation
      technique. The hydrogels were characterized by Fourier transform infrared (FT-IR)
      spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and
      scanning electron microscopy (SEM). FT-IR spectroscopy confirmed the grafting.
      XRD showed that the crystallinity of BC was reduced by grafting, whereas an
      increase in the thermal stability profile was observed in TGA. SEM showed that
      the hydrogels exhibited a highly porous morphology, which is suitable for drug
      loading. The hydrogels demonstrated a pH-responsive swelling behavior, with
      decreased swelling in acidic media, which increased with increase in pH of the
      media, reaching maximum swelling at pH 7. The release profile of the hydrogels
      was investigated in simulated gastric fluid (SGF) and simulated intestinal fluid
      (SIF). The hydrogels showed lesser release in SGF than in SIF, suggesting that
      hydrogels may be suitable drug carriers for oral controlled release of drug
      delivery in the lower gastrointestinal tract.

PMID- 23875789
TI  - Influence of application techniques on contact formation and voids in anterior
      resin composite restorations.
AB  - This study evaluated the influence of three different application techniques on
      contact formation and voids in anterior resin composite restorations. Artificial
      ivorine teeth were randomly assigned to three experimental groups, with 20
      specimens in each group. One operator performed all restorations using the Teflon
      tape, pull-through, or bioclear matrix technique. The treatment time required for
      each restoration was recorded. An examiner blinded to the treatment group
      performed the visual evaluation of six criteria, including proper contact
      formation. The restored teeth were cut to yield a total of 180 sections for
      microscopic evaluation. The Kruskal-Wallis procedure was performed to evaluate
      the significance of treatment time, number of voids, percent porosity area, and
      void diameter. There were significant differences in treatment time among the
      three groups (p<0.05). The bioclear matrix technique required the least time for
      the treatment of one diastema closure (p<0.05). The Teflon tape technique
      resulted in proper contact formation in 80% of specimens, a rate that was
      significantly lower than that associated with the pull-through and bioclear
      matrix techniques (p<0.05). Out of 540 imaging areas 160 images were free of
      voids. The number of voids and the percent porosity area were not significantly
      different among the three techniques (p>0.05). However, the mean void diameter
      was greater with the bioclear matrix technique compared to the other two
      techniques (p<0.05).

PMID- 23875788
TI  - Assessment of preoperative exercise capacity in hepatocellular carcinoma patients
      with chronic liver injury undergoing hepatectomy.
AB  - BACKGROUND: Cardiopulmonary exercise testing measures oxygen uptake at increasing
      levels of work and predicts cardiopulmonary performance under conditions of
      stress, such as after abdominal surgery. Dynamic assessment of preoperative
      exercise capacity may be a useful predictor of postoperative prognosis. This
      study examined the relationship between preoperative exercise capacity and event
      free survival in hepatocellular carcinoma (HCC) patients with chronic liver
      injury who underwent hepatectomy. METHODS: Sixty-one HCC patients underwent
      preoperative cardiopulmonary exercise testing to determine their anaerobic
      threshold (AT). The AT was defined as the break point between carbon dioxide
      production and oxygen consumption per unit of time (VO2). Postoperative events
      including recurrence of HCC, death, liver failure, and complications of cirrhosis
      were recorded. Univariate and multivariate analyses were performed to evaluate
      associations between 35 clinical factors and outcomes, and identify independent
      prognostic indicators of event-free survival and maintenance of Child-Pugh class.
      RESULTS: Multivariate analyses identified preoperative branched-chain amino
      acid/tyrosine ratio (BTR) <5, alanine aminotransferase level >=42 IU/l, and AT
      VO2 <11.5 ml/min/kg as independent prognostic indicators of event-free survival.
      AT VO2 <11.5 ml/min/kg and BTR <5 were identified as independent prognostic
      indicators of maintenance of Child-Pugh class. CONCLUSIONS: This study identified
      preoperative exercise capacity as an independent prognostic indicator of event
      free survival and maintenance of Child-Pugh class in HCC patients with chronic
      liver injury undergoing hepatectomy.

PMID- 23875790
TI  - Novel copper-catalyzed multicomponent cascade synthesis of iminocoumarin aryl
      methyl ethers.
AB  - A copper(I)-catalyzed one-pot synthesis of iminocoumarin aryl methyl ethers has
      been developed from ynal, phenol, and sulfonyl azide at ambient conditions via a
      cascade [3 + 2]-cycloaddition, 1,3-pseudopericyclic ketenimine rearrangement, 1,4
      conjugate addition, and aldol-type condensation. This protocol provides a
      potential route for the construction of a library of iminocoumarin aryl methyl
      ethers in good yields. 

PMID- 23875791
TI  - Carbohydrate use and reduction in number of balance beam falls: implications for
      mental and physical fatigue.
AB  - BACKGROUND: Artistic Gymnastics is a sport where athletes are frequently
      fatigued. One element that might influence this aspect is carbohydrate, an
      important energy substrate for the muscles and the CNS. Our goal was to
      investigate the influence of fatigue over artistic gymnastics athlete's
      performance and the effects of a carbohydrate supplementation on their
      performance. METHODS: We evaluated 15 athletes divided in 2 groups (control and
      fatigue) from 12 to 14 years old in two different experimental days. On the first
      day (water day), they did 5 sets of exercises on the balance beam (experimental
      protocol) ingesting only water, CG (control group) warmed up before the
      experimental protocol and FG (fatigue group) did a fatigue circuit, warm up
      exercises and then the experimental protocol. On the second day (carbohydrate
      day), we used the same protocol but CG ingested a sugar free flavored juice and
      FG ingested a 20% concentration maltodextrin solution before the protocol on the
      balance beam. RESULTS: We observed a greater number of falls from the balance
      beam from the FG on the first day (5.40 +/- 1.14 FG vs 3.33 +/- 1.37 CG; p =
      0.024) and a decrease in the number of falls on the second day (2.29 +/- 1.25 FG
      water day vs 5.40 +/- 1.14 FG carbohydrate day; p = 0.0013). Carbohydrate
      solution was able to supply muscle demands and improve the athlete's focus showed
      by the reduced number of falls.

PMID- 23875792
TI  - Pharmacokinetics and relative bioavailability of D-penicillamine in fasted and
      nonfasted dogs.
AB  - BACKGROUND: D-Penicillamine is the most commonly used copper-chelating agent in
      the treatment of copper-associated hepatitis in dogs. Response to therapy can be
      variable, and there is a lack of pharmacokinetic information available for dogs.
      Coadministering the drug with food to alleviate vomiting has been recommended for
      dogs, which contradicts recommendations for drug administration to humans.
      HYPOTHESIS: Coadministration of d-penicillamine with food decreases relative
      bioavailability and maximum plasma drug concentrations (C(max)) in dogs. ANIMALS:
      Nine purpose-bred dogs with a median body weight of 17.0 kg. METHODS: Dogs
      received D-penicillamine (12.5 mg/kg PO) fasted and with food in a randomized,
      crossover design. Blood samples were collected before and 0.25, 0.5, 1, 2, 3, 4,
      8, 12, and 24 hours after dosing. Total d-penicillamine concentrations were
      measured using liquid chromatography coupled with tandem quadrupole mass
      spectrometry. Pharmacokinetic parameters were calculated for each dog. RESULTS:
      Two fasted dogs (22%) vomited after receiving d-penicillamine. Mean C(max) +/-
      standard deviation (SD) was 8.7 +/- 3.1 MUg/mL (fasted) and 1.9 +/- 1.6 MUg/mL
      (fed). Mean area under the plasma concentration curve +/- SD was 16.9 +/- 5.9
      MUg/mL.h (fasted) and 4.9 +/- 3.4 MUg/mL.h (fed). There were significant
      reductions in relative bioavailability and C(max) in fed dogs (P < .001).
      CONCLUSIONS AND CLINICAL IMPORTANCE: Coadministration of d-penicillamine with
      food significantly decreases plasma drug concentrations in dogs. Decreased drug
      exposure could result in decreased copper chelation efficacy, prolonged therapy,
      additional cost, and greater disease morbidity. Administration of d-penicillamine
      with food cannot be categorically recommended without additional studies.

PMID- 23875793
TI  - Controlling mixed-protein adsorption layers on colloidal alumina particles by
      tailoring carboxyl and hydroxyl surface group densities.
AB  - We show that different ratios of bovine serum albumin (BSA) and lysozyme (LSZ)
      can be achieved in a mixed protein adsorption layer by tailoring the amounts of
      carboxyl (-COOH) and aluminum hydroxyl (AlOH) groups on colloidal alumina
      particles (d50 ~ 180 nm). The particles are surface-functionalized with -COOH
      groups, and the resultant surface chemistry, including the remaining AlOH groups,
      is characterized and quantified using elemental analysis, zeta potential
      measurements, acid-base titration, IR spectroscopy, electron microscopy, nitrogen
      adsorption, and dynamic light scattering. BSA and LSZ are subsequently added to
      the particle suspensions, and protein adsorption is monitored by in situ zeta
      potential measurements while being quantified by UV spectroscopy and gel
      electrophoresis. A comparison of single-component and sequential protein
      adsorption reveals that BSA and LSZ have specific adsorption sites: BSA adsorbs
      primarily via AlOH groups, whereas LSZ adsorbs only via -COOH groups (1-2 -COOH
      groups on the particle surface is enough to bind one LSZ molecule). Tailoring
      such groups on the particle surface allows control of the composition of a mixed
      BSA and LSZ adsorption layer. The results provide further insight into how
      particle surface chemistry affects the composition of protein adsorption layers
      on colloidal particles and is valuable for the design of such particles for
      biotechnological and biomedical applications. 

PMID- 23875794
TI  - The genetic landscapes of autism spectrum disorders.
AB  - The autism spectrum disorders (ASD) are characterized by impairments in social
      interaction and stereotyped behaviors. For the majority of individuals with ASD,
      the causes of the disorder remain unknown; however, in up to 25% of cases, a
      genetic cause can be identified. Chromosomal rearrangements as well as rare and
      de novo copy-number variants are present in ~10-20% of individuals with ASD,
      compared with 1-2% in the general population and/or unaffected siblings. Rare and
      de novo coding-sequence mutations affecting neuronal genes have also been
      identified in ~5-10% of individuals with ASD. Common variants such as single
      nucleotide polymorphisms seem to contribute to ASD susceptibility, but, taken
      individually, their effects appear to be small. Despite a heterogeneous genetic
      landscape, the genes implicated thus far-which are involved in chromatin
      remodeling, metabolism, mRNA translation, and synaptic function-seem to converge
      in common pathways affecting neuronal and synaptic homeostasis. Animal models
      developed to study these genes should lead to a better understanding of the
      diversity of the genetic landscapes of ASD. 

PMID- 23875795
TI  - The genomics of memory and learning in songbirds.
AB  - Songbirds have unique value as a model for memory and learning. In their natural
      social life, they communicate through vocalizations that they must learn to
      produce and recognize. Song communication elicits abrupt changes in gene
      expression in regions of the forebrain responsible for song perception and
      production--what is the functional significance of this genomic response? For 20
      years, the focus of research was on just a few genes [primarily ZENK, now known
      as egr1 (early gene response 1)]. Recently, however, DNA microarrays have been
      developed and applied to songbird behavioral research, and in 2010 the initial
      draft assembly of the zebra finch genome was published. Together, these new data
      reveal that the genomic involvement in song processing is far more complex than
      anticipated. The concepts of neurogenomic computation and biological embedding
      are introduced as frameworks for future research.

PMID- 23875796
TI  - Return of individual research results and incidental findings: facing the
      challenges of translational science.
AB  - The debate over return of individual research results and incidental findings to
      study participants is a key frontier in research ethics and practice. This is
      fundamentally a problem of translational science-a question of when information
      about an individual that is generated in research should be communicated for
      clinical attention, particularly as technologies such as whole-genome sequencing
      and whole-exome sequencing are increasingly used in clinical care. There is
      growing consensus that investigators should offer participants at least those
      individual findings of high clinical importance and actionability. Increasing
      attention to what information biobanks and secondary researchers owe people who
      provide data and specimens offers an opportunity to treat these source
      individuals as research partners. Cutting-edge issues include return of results
      in pediatric populations and return to kin and family, both before and after the
      death of the proband, as well as how to manage incidental findings in clinical
      sequencing. Progress will require an understanding of the continuum linking
      research and clinical care and developing standards and models for return. 

PMID- 23875797
TI  - The spatial organization of the human genome.
AB  - In vivo, the human genome functions as a complex, folded, three-dimensional
      chromatin polymer. Understanding how the human genome is spatially organized and
      folded inside the cell nucleus is therefore central to understanding how genes
      are regulated in normal development and dysregulated in disease. Established
      light microscopy-based approaches and more recent molecular chromosome
      conformation capture methods are now combining to give us unprecedented insight
      into this fascinating aspect of human genomics. 

PMID- 23875798
TI  - The RASopathies.
AB  - The RASopathies are a clinically defined group of medical genetic syndromes
      caused by germline mutations in genes that encode components or regulators of the
      Ras/mitogen-activated protein kinase (MAPK) pathway. These disorders include
      neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple
      lentigines, capillary malformation-arteriovenous malformation syndrome, Costello
      syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. Because of the
      common underlying Ras/MAPK pathway dysregulation, the RASopathies exhibit
      numerous overlapping phenotypic features. The Ras/MAPK pathway plays an essential
      role in regulating the cell cycle and cellular growth, differentiation, and
      senescence, all of which are critical to normal development. Therefore, it is not
      surprising that Ras/MAPK pathway dysregulation has profound deleterious effects
      on both embryonic and later stages of development. The Ras/MAPK pathway has been
      well studied in cancer and is an attractive target for small-molecule inhibition
      to treat various malignancies. The use of these molecules to ameliorate
      developmental defects in the RASopathies is under consideration. 

PMID- 23875800
TI  - Growing up in the genomic era: implications of whole-genome sequencing for
      children, families, and pediatric practice.
AB  - Whole-genome sequencing (WGS) has advanced to a point where it is beginning to be
      integrated into pediatric practice. With little consensus on how to maximize the
      benefits of WGS for children, there is a growing need for focused efforts that
      connect researchers, clinicians, and families to chart a path forward. To
      illustrate relevant concerns, two contrasting applications of pediatric WGS are
      explored: clinical use with children who have undiagnosed conditions, and
      population-based screening. Specific challenges for health care services, policy
      development, and the well-being of children are discussed in light of current
      research. In the interest of ensuring evidence-based pediatric WGS, strategies
      are identified for advancing our understanding of what it means for children to
      grow up with WGS results guiding their health care. 

PMID- 23875802
TI  - The role of patient advocacy organizations in shaping genomic science.
AB  - Patient advocacy organizations (PAOs) are nonprofit groups that represent
      patients and families affected by a significant medical condition or disease. We
      review some of the different approaches that humanities and social researchers
      use to study PAOs. Drawing on this recent scholarship, we describe some
      contemporary patient groups and explore how PAOs can collaborate with biomedical
      researchers to advance genomic science. We highlight research that aims to
      describe how PAOs are contributing to multiple aspects of biomedical research,
      including study design, definition of research goals, data collection and
      analysis, dissemination of results, and research funding. We also describe
      several challenges that genomic researchers may encounter in collaborations with
      PAOs. Throughout our review, we focus on the manner in which new PAO roles
      challenge traditional boundaries between researchers and subjects, thereby
      redefining the relationship of patients to science. We consider how this shift
      may affect our view of scientific collaborations and impact genomic researchers
      in the future. 

PMID- 23875799
TI  - Translational genetics for diagnosis of human disorders of sex development.
AB  - Disorders of sex development (DSDs) are congenital conditions with discrepancies
      between the chromosomal, gonadal, and phenotypic sex of the individual. Such
      disorders have historically been difficult to diagnose and cause great stress to
      patients and their families. Genetic analysis of human samples has been
      instrumental in elucidating the molecules and pathways involved in the
      development of the bipotential gonad into a functioning testis or ovary. However,
      many DSD patients still do not receive a genetic diagnosis. New genetic and
      genomic technologies are expanding our knowledge of the underlying mechanism of
      DSDs and opening new avenues for clinical diagnosis. We review the genetic
      technologies that have elucidated the genes that are well established in sex
      determination in humans, discuss findings from more recent genomic technologies,
      and propose a new paradigm for clinical diagnosis of DSDs. 

PMID- 23875803
TI  - The genetics of melanoma: recent advances.
AB  - Cutaneous malignant melanoma results from the interplay of genetic, host, and
      environmental factors. Genetic factors implicated in melanoma etiology include
      inherited high-, intermediate-, and low-risk susceptibility genes as well as
      numerous somatic mutations in melanoma tumors. CDKN2A is the major high-risk
      melanoma susceptibility gene identified to date. Recent identification of low
      risk loci has been accomplished predominantly through genome-wide association
      studies. Whole-exome and whole-genome studies have identified numerous genes
      somatically altered in melanoma tumors and highlighted a higher mutation load in
      melanoma tumors compared with those in other cancers. This higher load is
      believed to be attributable to the preponderance of cytosine-to-thymine
      nucleotide substitutions as a result of UV radiation exposure. Technological
      advances, particularly next-generation sequencing, have increased the
      opportunities for germline and somatic gene discovery in melanoma and are opening
      up new avenues for understanding melanoma pathogenesis as well as leading to new
      opportunities for treatment. 

PMID- 23875801
TI  - Major histocompatibility complex genomics and human disease.
AB  - Over several decades, various forms of genomic analysis of the human major
      histocompatibility complex (MHC) have been extremely successful in picking up
      many disease associations. This is to be expected, as the MHC region is one of
      the most gene-dense and polymorphic stretches of human DNA. It also encodes
      proteins critical to immunity, including several controlling antigen processing
      and presentation. Single-nucleotide polymorphism genotyping and human leukocyte
      antigen (HLA) imputation now permit the screening of large sample sets, a
      technique further facilitated by high-throughput sequencing. These methods
      promise to yield more precise contributions of MHC variants to disease. However,
      interpretation of MHC-disease associations in terms of the functions of variants
      has been problematic. Most studies confirm the paramount importance of class I
      and class II molecules, which are key to resistance to infection. Infection is
      likely driving the extreme variation of these genes across the human population,
      but this has been difficult to demonstrate. In contrast, many associations with
      autoimmune conditions have been shown to be specific to certain class I and class
      II alleles. Interestingly, conditions other than infections and autoimmunity are
      also associated with the MHC, including some cancers and neuropathies. These
      associations could be indirect, owing, for example, to the infectious history of
      a particular individual and selective pressures operating at the population
      level. 

PMID- 23875804
TI  - Lipidomic fingerprint of almonds (Prunus dulcis L. cv Nonpareil) using TiO2
      nanoparticle based matrix solid-phase dispersion and MALDI-TOF/MS and its
      potential in geographical origin verification.
AB  - A matrix solid-phase dispersion (MSPD) procedure with titanium dioxide (TiO2)
      nanoparticles (NP) as sorbent was developed for the selective extraction of
      phospholipids from almond samples, and matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) was employed for
      analysis. A remarkable increase in the signals of phospholipid accompanied by a
      decrease in those of triacylglycerols and diacylglycerols was observed in the
      relevant mass spectra. The proposed method was applied to five batches of almonds
      originating from four geographical areas, whereas principal component analysis
      (PCA) was utilized to normalize the relative amounts of the identified
      phospholipid species. The results indicated that the lipidomic fingerprint of
      almonds was successfully established by the negative ion mode spectrum, and the
      ratio of m/z 833.6 to 835.6 as well as m/z 821.6 could be introduced as potential
      markers for the differentiation of the tested almonds with different geographical
      origins. The whole method is of great promise for selective separation of
      phospholipids from nonphospholipids, especially the glycerides, and superior in
      fast screening and characterization of phospholipids in almond samples. 

PMID- 23875806
TI  - The effect of depressive symptoms on the association between radiographic
      osteoarthritis and knee pain: a cross-sectional study.
AB  - BACKGROUND: The progressive nature of knee osteoarthritis (OA) leads to not only
      to physical but also to psychosocial decline; this aspect can influence knee pain
      experience, manifestations and inevitably diagnostic accuracy. METHODS: Data on
      663 subjects was obtained by interview using a structured questionnaire on
      social, demographic, behavioural and clinical data. Painful knee was assessed
      regarding having pain: ever, in the last year, in the last 6 months and in the
      last month. Using factor analysis, participants were graded using a knee pain
      score, with higher scores representing more symptomatology. Depressive symptoms
      were evaluated with the Beck Depressive Inventory (BDI), and radiographic knee OA
      was classified using the Kellgren Lawrence (KL) scale; those with KL >= 2 were
      considered as having radiographic OA. RESULTS: Knee pain was reported by 53.2% of
      those with radiographic KL >= 2 and by 33.2% of those with radiographic KL < 2.
      The prevalence of depressive symptoms (BDI > 14) was 19.9% among participants
      with radiographic KL >= 2 and 12.6% among those with radiographic KL < 2 (p =
      0.01). The association of knee pain with radiographic knee OA was higher in
      higher pain scores and in participants without depressive symptoms. Among
      participants with BDI <= 14 the likelihood ratio to identify patients with
      radiographic knee OA increased with increased pain scores: 1.02 for score 1; 2.19
      for score 2 and 7.34 when participants responded positively to all pain questions
      (score 3). Among participants with depressive symptoms (BDI > 14) likelihood
      ratios were 0.51, 1.92, 1.82, respectively. The results were similar for both
      genders. CONCLUSIONS: Knee pain scores increased ability to identify participants
      with radiographic KL >= 2 in both sexes. However, the presence of depressive
      symptoms impairs the ability of knee pain complaints to identify patients with
      radiographic OA.

PMID- 23875807
TI  - Characterization of cyclopentyllithium and cyclopentyllithium tetrahydrofuran
      complex.
AB  - The solid-state structures of unsolvated, hexameric cyclopentyllithium and
      tetrameric cyclopentyllithium tetrahydrofuran solvate were determined by single
      crystal X-ray diffraction. Cyclopentyllithium easily crystallized in hydrocarbon
      solvents. Solution-state structural analyses of cyclopentyllithium and
      cyclopentyllithium-tetrahydrofuran complexes in toluene-d8 were also carried out
      by diffusion-ordered NMR spectroscopy with diffusion coefficient-formula weight
      correlation analyses and other one- and two-dimensional NMR techniques. The
      solution-state studies suggest that unsolvated cyclopentyllithium exists as
      hexamer and tetramer equilibrating with each other. Upon solvation with
      tetrahydrofuran, cyclopentyllithium exists mostly as a tetrahydrofuran
      tetrasolvated tetramer. 

PMID- 23875808
TI  - Analysis of psychoactive cathinones and tryptamines by electrospray ionization
      atmospheric pressure ion mobility time-of-flight mass spectrometry.
AB  - The ability to use positive ion monitoring mode with an atmospheric pressure ion
      mobility time-of-flight mass spectrometer (APIM(tof)MS) to detect psychoactive
      cathinones and tryptamines from aqueous phase samples was evaluated. The study
      used a traditional electrospray ionization (ESI) source for sample introduction
      and ionization. A total of four cathinones (mephedrone, butylone, 4-Me-PPP, and 4
      MEC) and five tryptamines (5-EtO-DPT, 5-EtO-DALT, 5-EtO-MIPT, 5-EtO-ALCHT, and 5
      EtO-2MALET) were investigated, and we report on parent ions, collision induced
      dissociation (CID) fragment ions, reduced mobility (Ko), mass flight times, and
      detection limits obtained from a single instrument run for the psychoactive
      substances. Detection limits reported ranged from 3 to 11 MUM concentration for
      the compounds studied. This detection limit range corresponded to 1-5 ng of
      material needed for improved detection on the instrument. This article
      demonstrates that it was possible to use a single instrument platform for the
      separation, detection, and identification of cathinones and tryptamines in less
      than 1 min. The application holds great promise for detecting and identifying a
      new class of drugs often referred to as "bath salts" or "legal highs" distributed
      over the Internet. 

PMID- 23875809
TI  - Regular consumption of both vitamin D- and calcium- and vitamin D-fortified
      yogurt drink is equally accompanied by lowered blood lipoprotein (a) and elevated
      apoprotein A1 in subjects with type 2 diabetes: a randomized clinical trial.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the major morbidity and cause of death
      in diabetic subjects. Observational studies have shown the association of low
      vitamin D status with poor glycemic control, atherogenic lipid profile, and CVD.
      However, the possible link between circulating 25-hydroxycholecalciferol and
      apoproteins (Apo A1 and B) and the atherogenic lipoprotein (a) [Lp(a)] has not
      been documented to date. METHODS: Ninety subjects with type 2 diabetes (T2D) aged
      30-60 years from both sexes were randomly allocated to one of the 3 groups to
      receive 2 bottles a day of either (1) plain doogh (PD; containing 150 mg calcium
      and no detectable vitamin D/250 mL); (2) vitamin D-fortified doogh (DD;
      containing 150 mg calcium and 500 IU vitamin D/250 mL); or (3) calcium- and
      vitamin D-fortified doogh (CDD; containing 250 mg calcium and 500 IU vitamin
      D/250 mL) for 12 weeks. Anthropometric, dietary, and laboratory assessments,
      including Apo A1, Apo B, and Lp(a), were done. RESULTS: Improvement of vitamin D
      status in DD and CDD groups, compared to PD, resulted in a significant increase
      in Apo A1 (mean changes 0.22 +/- 0.38, 0.20 +/- 0.27 and 0.01 +/- 0.35 g/L,
      respectively, p = 0.047) and a significant decrease in serum Lp(a) (mean changes 
      0.08 +/- 0.30, -0.08 +/- 0.31, and 0.14 +/- 0.25 MUmol/L, respectively, p =
      0.011). There was no significant difference between DD and CDD groups. Serum Apo
      B did not change significantly in any of the groups. CONCLUSIONS: Significant
      amelioration of serum Apo A1 and Lp(a) following improvement of vitamin D status
      in T2D subjects may have preventive implications against long-term diabetic
      complications, notably CVD. This trial was registered at ClinicalTrials.gov as
      NTC01229891.

PMID- 23875805
TI  - SOD therapeutics: latest insights into their structure-activity relationships and
      impact on the cellular redox-based signaling pathways.
AB  - SIGNIFICANCE: Superoxide dismutase (SOD) enzymes are indispensable and ubiquitous
      antioxidant defenses maintaining the steady-state levels of O2.(-); no wonder,
      thus, that their mimics are remarkably efficacious in essentially any animal
      model of oxidative stress injuries thus far explored. RECENT ADVANCES: Structure
      activity relationship (half-wave reduction potential [E1/2] versus log kcat),
      originally reported for Mn porphyrins (MnPs), is valid for any other class of SOD
      mimics, as it is dominated by the superoxide reduction and oxidation potential.
      The biocompatible E1/2 of ~+300 mV versus normal hydrogen electrode (NHE) allows
      powerful SOD mimics as mild oxidants and antioxidants (alike O2.(-)) to readily
      traffic electrons among reactive species and signaling proteins, serving as fine
      mediators of redox-based signaling pathways. Based on similar thermodynamics,
      both SOD enzymes and their mimics undergo similar reactions, however, due to
      vastly different sterics, with different rate constants. CRITICAL ISSUES:
      Although log kcat(O2.(-)) is a good measure of therapeutic potential of SOD
      mimics, discussions of their in vivo mechanisms of actions remain mostly of
      speculative character. Most recently, the therapeutic and mechanistic relevance
      of oxidation of ascorbate and glutathionylation and oxidation of protein thiols
      by MnP-based SOD mimics and subsequent inactivation of nuclear factor kappaB has
      been substantiated in rescuing normal and killing cancer cells. Interaction of
      MnPs with thiols seems to be, at least in part, involved in up-regulation of
      endogenous antioxidative defenses, leading to the healing of diseased cells.
      FUTURE DIRECTIONS: Mechanistic explorations of single and combined therapeutic
      strategies, along with studies of bioavailability and translational aspects, will
      comprise future work in optimizing redox-active drugs.

PMID- 23875812
TI  - Nanocomposite pattern-mediated magnetic interactions for localized deposition of
      nanomaterials.
AB  - We present a method to create, align, and locate magnetic wires throughout and on
      the surface of patterned polymer matrices, following the magnetophoretic
      transport and self-assembly of ferromagnetic nanoparticles under a static
      magnetic field during laser photopolymerization of monomer/nanoparticle casted
      solutions. The resulting films have the ability to attract and immobilize small
      quantities of magnetic nanomaterials locally on the ferromagnetic wires, as
      proved by a detailed topography study. Magnetic studies on the films before and
      after the spontaneous deposition, demonstrate that the deposited nanomaterials
      alter significantly the magnetic character of the system, making thus possible
      their macroscopic identification. This offers the possibility to realize sensing
      devices based on hybrid materials with magnetic properties. 

PMID- 23875811
TI  - TRPC6 channel-mediated neurite outgrowth in PC12 cells and hippocampal neurons
      involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling.
AB  - The non-selective cationic transient receptor canonical 6 (TRPC6) channels are
      involved in synaptic plasticity changes ranging from dendritic growth, spine
      morphology changes and increase in excitatory synapses. We previously showed that
      the TRPC6 activator hyperforin, the active antidepressant component of St. John's
      wort, induces neuritic outgrowth and spine morphology changes in PC12 cells and
      hippocampal CA1 neurons. However, the signaling cascade that transmits the
      hyperforin-induced transient rise in intracellular calcium into neuritic
      outgrowth is not yet fully understood. Several signaling pathways are involved in
      calcium transient-mediated changes in synaptic plasticity, ranging from
      calmodulin-mediated Ras-induced signaling cascades comprising the mitogen
      activated protein kinase, PI3K signal transduction pathways as well as Ca(2+)
      /calmodulin-dependent protein kinase II (CAMKII) and CAMKIV. We show that several
      mechanisms are involved in TRPC6-mediated synaptic plasticity changes in PC12
      cells and primary hippocampal neurons. Influx of calcium via TRPC6 channels
      activates different pathways including Ras/mitogen-activated protein
      kinase/extracellular signal-regulated kinases, phosphatidylinositide 3
      kinase/protein kinase B, and CAMKIV in both cell types, leading to cAMP-response
      element binding protein phosphorylation. These findings are interesting not only
      in terms of the downstream targets of TRPC6 channels but also because of their
      potential to facilitate further understanding of St. John's wort extract-mediated
      antidepressant activity. Alterations in synaptic plasticity are considered to
      play an important role in the pathogenesis of depression. Beside several other
      proteins, TRPC6 channels regulate synaptic plasticity. This study demonstrates
      that different pathways including Ras/MEK/ERK, PI3K/Akt, and CAMKIV are involved
      in the improvement of synaptic plasticity by the TRPC6 activator hyperforin, the
      antidepressant active constituent of St. John's wort extract. 

PMID- 23875810
TI  - Impact of low-dose dipyridamole injection on adenosine test after pulmonary vein
      isolation.
AB  - BACKGROUND: Dipyridamole increases the levels of extracellular adenosine. The
      study investigates the impact of low-dose intravenous dipyridamole on adenosine
      test after pulmonary vein (PV) isolation (PVI). METHODS AND RESULTS: This
      prospective study included 12 paroxysmal atrial fibrillation (AF) patients (61 +/
      12 years; nine men) who underwent PVI at the first procedure. Transient PV
      reconnection was provoked by adenosine test in 4/48 PVs. In 44 PVs without
      reconnection, intravenous infusion of low-dose (10 mg) dipyridamole preceded the
      adenosine test. Additional six patients (PVs) with transient dormant conduction
      were included. Among the total 10 PVs with transient reconnection, it was
      eliminated by radiofrequency (RF) application(s) until no dormant conduction was
      exposed by adenosine test(s) in five PVs. Then, dipyridamole potentiated
      adenosine test was undertaken to provoke dormant conduction (group 1). In the
      remaining five PVs, dipyridamole potentiated adenosine test was followed by RF
      elimination of conduction gap and repeat adenosine test to confirm complete
      elimination (group 2). Low-dose dipyridamole prolonged the duration of adenosine
      induced atrioventricular block without vasodilatatory hypotension. There was no
      evidence of reconnection in 44 PVs without dormant conduction and in group 1
      wherein transient reconnection was eliminated by 4.8 +/- 3.2 RF applications in
      8.8 +/- 3.0 minutes and adenosine injected 3.1 +/- 1.8 times. In group 2,
      dipyridamole plus adenosine test revealed the same dormant conduction that
      persisted longer than during adenosine alone. It was eliminated by single RF
      application in 3.4 +/- 0.9 minutes, and adenosine was injected once. CONCLUSIONS:
      Low-dose dipyridamole safely prolongs the electrophysiological effects of
      adenosine test without provoking additional PV reconnection. This allows
      sustained visualization and facilitates complete RF elimination of the electrical
      conduction gap.

PMID- 23875813
TI  - Exploring the later life relationship between adults with cerebral palsy and
      their non-disabled siblings.
AB  - PURPOSE: Adults with moderate or severe cerebral palsy often require significant
      lifetime support from family and formal services. The aim of this study was to
      use a life course approach to explore how previous life experiences impact on the
      later life relationships of people with moderate to severe cerebral palsy aged 40
      years and over and their non-disabled siblings. METHOD: Twelve adults with
      moderate to severe cerebral palsy and 16 of their non-disabled siblings were
      interviewed twice to explore their relationships. Constructivist grounded theory
      method was used to analyse the data. RESULTS: Four themes were identified as
      important in understanding these later life sibling relationships: sharing
      childhood experiences, contact in adulthood, diminishing parental role and
      increasing support needs. CONCLUSIONS: The life course approach indicated that
      siblings' growing up together was important for the development and maintenance
      of emotional closeness later in life. Emotional closeness and familial obligation
      were important factors in motivating siblings with and without cerebral palsy to
      maintain or re-establish contact with each other in adulthood. Maintenance of
      sibling relationships in later life is dependent on health, proximity and the
      ability to keep in contact with each other. Implications for Rehabilitation As
      adults with severe cerebral palsy live longer, their relationships with non
      disabled siblings often take on increased importance and particularly as their
      parents may be no longer able to provide support. Service providers have a role
      in helping ageing siblings with and without disability to maintain and build
      their relationships, for example, by supporting geographically distant siblings
      to keep in touch. Service providers have a role in supporting the person with a
      disability and their siblings to make plans for the future.

PMID- 23875814
TI  - Influence of fear of falling on gait and balance in Parkinson's disease.
AB  - PURPOSE: To study the relationship of fear of falling (FoF) with gait
      characteristics and balance in individuals with Parkinson's disease (PD). METHOD:
      Seventy-nine non-demented individuals (62 males) with PD were studied. Their mean
      age was 69.22 +/- 8.93 years. The average time since diagnosis was 8.27 +/- 5.31
      years. FoF was assessed by the Activities-specific Balance Confidence (ABC) Scale
      in which high scores indicate less FoF. Gait was measured using a computerized
      walkway. Balance was measured by timed tests including the 5-step test, 360
      degree turn, timed sideways walk, and timed up and go test. Participants were
      divided into two groups based on their ABC score (high FoF, ABC score <69; low
      FoF, ABC score >=69). Gait characteristics and balance measures of the two groups
      were compared. RESULTS: Gait speed and stride length for forward walking (p <
      0.0005 for both) and backward walking (p = 0.001 and 0.002, respectively) were
      lower for those with a high level of FoF compared to those with a low level of
      FoF. The time to take five steps (p = 0.025), time to turn (p < 0.0005), time to
      walk sideways (p = 0.001), and time to complete the up and go test (p = 0.003)
      were longer in those with a high level of FoF than in those with a low level of
      FoF. Number of steps to complete the turn (p = 0.001) and steps to walk sideways
      (p = 0.002) were greater in those with a high level of FoF than in those with a
      low level FoF. CONCLUSIONS: Gait and balance of individuals with PD with a high
      level of FoF were poorer than those with a low level of FoF, regardless of
      previous fall history. Implications for Rehabilitation The results demonstrates
      that fear of falling (FoF) is related to gait and balance in individuals with PD.
      Clinicians should be aware that FoF has a negative impact on gait and balance in
      individuals with PD.

PMID- 23875815
TI  - Cross-border impacts of the restriction of hazardous substances: a perspective
      based on Japanese solders.
AB  - Despite the relevance of the global economy, Regulatory Impact Assessments of the
      restriction of hazardous substances (RoHS) in the European Union (EU) are based
      only on domestic impacts. This paper explores the cross-border environmental
      impacts of the RoHS by focusing on the shifts to lead-free solders in Japan,
      which exports many electronics to the EU. The regulatory impacts are quantified
      by integrating a material flow analysis for metals constituting a solder with a
      scenario analysis with and without the RoHS. The results indicate that the EU
      regulation, the RoHS, has triggered shifts in Japan to lead-free solders, not
      only for electronics subject to this regulation, but for other products as well.
      We also find that the RoHS leads to a slow reduction in environmental emissions
      of the target, lead, but results in a rapid increase in the use of tin and silver
      in lead-free solders. This indicates the importance of assessing potential
      alternative substances, the use of which may increase as a result of adhering to
      the RoHS. The latter constitutes a negative impact because of recent concerns
      regarding resource criticality. 

PMID- 23875816
TI  - Influence of astaxanthin, emulsifier and organic phase concentration on
      physicochemical properties of astaxanthin nanodispersions.
AB  - BACKGROUND: The emulsification-evaporation method was used to prepare astaxanthin
      nanodispersions using a three-component emulsifier system composed of Tween 20,
      sodium caseinate and gum Arabic. Using Response-surface methodology (RSM), we
      studied the main and interaction effects of the major emulsion components,
      namely, astaxanthin concentration (0.02-0.38 wt %, x1), emulsifier concentration
      (0.2-3.8 wt %, x2) and organic phase (dichloromethane) concentration (2-38 wt %,
      x3) on nanodispersion characteristics. The physicochemical properties considered
      as response variables were: average particle size (Y1), PDI (Y2) and astaxanthin
      loss (Y3). RESULTS: The results indicated that the response-surface models were
      significantly (p < 0.05) fitted for all studied response variables. The fitted
      polynomial regression models for the prediction of variations in the response
      variables showed high coefficients of determination (R2 > 0.930) for all
      responses. The overall optimum region resulted in a desirable astaxanthin
      nanodispersions obtained with the concentrations of 0.08 wt % astaxanthin, 2.5 wt
      % emulsifier and 11.5 wt % organic phase. CONCLUSION: No significant differences
      were found between the experimental and predicted values, thus certifying the
      adequacy of the Response-surface models developed for describing the changes in
      physicochemical properties as a function of main emulsion component
      concentrations.

PMID- 23875817
TI  - Vertical nontransovarial transmission of Bartonella in fleas.
AB  - Pathogens use diverse pathways to infect host populations by vertical and/or
      horizontal routes. Horizontal transmission of bacteria belonging to the
      Bartonella genus via haematophagous vectors is well known. Vertical transmission
      of Bartonella species was also suggested to occur but its routes remain to be
      unveiled. In a previous study, we showed the absence of transovarial transmission
      of Bartonella species OE 1-1 in Xenopsylla ramesis fleas, and that fleas feeding
      on Bartonella-positive jirds produced Bartonella-positive gut voids. This current
      study aimed to investigate whether vertical nontransovarial transmission of
      Bartonella occurs in fleas. For this aim, the X. ramesis-Bartonella sp. OE 1-1
      model was used. Four groups of fleas including Bartonella-positive and Bartonella
      negative female fleas and larval offspring had access to either Bartonella
      negative or Bartonella-positive gut voids and faeces. Sixteen per cent of flea
      offspring that had access to Bartonella-positive faeces and gut voids became
      Bartonella positive. Our findings demonstrate that Bartonella-positive flea
      faeces and gut voids are proper infection sources for flea larvae and indicate
      that vertical nontransovarial transmission of bartonellae occurs in fleas. This
      information broadens our understanding of Bartonella transmission routes in flea
      vectors and enlightens pathways of bartonellae transmission and maintenance in
      flea populations in nature. 

PMID- 23875818
TI  - Optimal timing of prophylactic antibiotic for cesarean delivery: a randomized
      comparative study.
AB  - AIM: Cesarean delivery is associated with a significantly higher postoperative
      infection rate than that following vaginal birth and other surgical procedures.
      This study compared whether antibiotic prophylaxis administered preoperatively
      was more effective in preventing infectious morbidity following cesarean delivery
      than administration at cord clamping. MATERIAL AND METHODS: In a randomized
      comparative trial, 953 women with a period of gestation of more than 34 weeks,
      scheduled to have cesarean section, were randomly assigned to the prophylactic
      single-dose antibiotic administration either preoperatively (study group) or at
      cord clamping (control group). Primary outcome measure was postoperative maternal
      infectious morbidity and secondary outcome measures were neonatal complications,
      and postoperative maternal hospital stay and stay of neonates in the neonatal
      intensive care unit. RESULTS: Wound complications in the form of indurations,
      erythema and discharge, were significantly fewer in the study group as compared
      to the control group (10/476 vs 25/477, P = 0.010, conditional maximum likelihood
      estimate of odds ratio = 0.388 and 95% confidence interval = 0.175-0.805). Women
      in the study group also had fewer incidents of endomyometritis when compared to
      the control group (1.47% vs 3.56%; P = 0.041; conditional maximum likelihood
      estimate of odds ratio = 0.404). There was no significant difference in neonatal
      outcomes between the two groups. Mean postoperative stay of mothers in hospital
      was significantly shorter in the study group (P = 0.009, 95% confidence interval
      = -0.368 to -0.052) but neonatal intensive care unit stay of neonates was similar
      in both groups. CONCLUSION: Administration of prophylactic antibiotic at 30-60
      min before skin incision resulted in better maternal outcome when infectious
      morbidity and postoperative hospital stay were concerned, without influencing the
      neonatal outcome.

PMID- 23875819
TI  - Characterization of water sorption, solubility, and roughness of silorane- and
      methacrylate-based composite resins.
AB  - OBJECTIVE: The objective of this study was to evaluate the surface roughness
      (SR), water sorption (WS), and solubility (SO) of four composite resins after
      finishing/polishing and after one year of water storage. MATERIALS AND METHODS:
      Two low-shrinkage composites (Filtek Silorane [3M ESPE] and Aelite LS [Bisco
      Inc]) and two composites of conventional formulations (Heliomolar and Tetric N
      Ceram [Ivoclar Vivadent]) were tested. Their respective finishing and polishing
      systems (Sof-Lex Discs, 3M ESPE; Finishing Discs Kit, Bisco Inc; and Astropol F,
      P, HP, Ivoclar Vivadent) were used according to the manufacturers' instructions.
      Ten disc-shaped specimens of each composite resin were made for each evaluation.
      Polished surfaces were analyzed using a profilometer after 24 hours and one year.
      For the WS and SO, the discs were stored in desiccators until constant mass was
      achieved. Specimens were then stored in water for seven days or one year, at
      which time the mass of each specimen was measured. The specimens were dried again
      and dried specimen mass determined. The WS and SO were calculated from these
      measurements. Data were analyzed by two-way analysis of variance and Tukey post
      hoc test (alpha=0.05). RESULTS: Filtek Silorane showed the lowest SR, WS, and SO
      means. Water storage for one year increased the WS means for all composite resins
      tested. CONCLUSIONS: The silorane-based composite resin results were better than
      those obtained for methacrylate-based resins. One-year water storage did not
      change the SR and SO properties in any of the composite resins.

PMID- 23875820
TI  - Infection with Panola Mountain Ehrlichia sp. in a dog with atypical lymphocytes
      and clonal T-cell expansion.

PMID- 23875821
TI  - Web intervention for OEF/OIF veterans with problem drinking and PTSD symptoms: a
      randomized clinical trial.
AB  - OBJECTIVE: Veterans who served in Operation Enduring Freedom (OEF) and Operation
      Iraqi Freedom (OIF) commonly experience alcohol misuse and symptoms of
      posttraumatic stress disorder (PTSD) following their return from deployment to a
      war zone. We conducted a randomized clinical trial to evaluate the efficacy of a
      newly developed, 8-module, self-management web intervention (VetChange) based on
      motivational and cognitive-behavioral principles to reduce alcohol consumption,
      alcohol-related problems, and PTSD symptoms in returning combat veterans. METHOD:
      Six hundred participants, recruited through targeted Facebook ads, were
      randomized to either an Initial Intervention Group (IIG; n = 404) or a Delayed
      Intervention Group (DIG; n = 196) that waited 8 weeks for access to VetChange.
      Primary outcome measures were Drinks per Drinking Day, Average Weekly Drinks,
      Percent Heavy Drinking Days, and PTSD symptoms. Intent-to-treat analyses compared
      changes in outcome measures over time between IIG and DIG as well as within-group
      changes. RESULTS: IIG participants demonstrated greater reductions in drinking (p
      < .001 for each measure) and PTSD symptoms (p = .009) between baseline and end-of
      intervention than did DIG participants between baseline and the end of the
      waiting period. DIG participants showed similar improvements to those in IIG
      following participation in VetChange. Alcohol problems were also reduced within
      each group between baseline and 3-month follow-up. CONCLUSIONS: Results indicate
      that VetChange is effective in reducing drinking and PTSD symptoms in OIF/OEF
      veterans. Further studies of VetChange are needed to assess web-based recruitment
      and retention methods and to determine VetChange's effectiveness in demographic
      and clinical sub-populations of returning veterans.

PMID- 23875822
TI  - Narrative meaning making is associated with sudden gains in psychotherapy
      clients' mental health under routine clinical conditions.
AB  - OBJECTIVE: The present study had two aims: (a) to replicate previous findings
      regarding the characteristics of sudden gains (SGs) in psychotherapy under
      routine clinical conditions and (b) to examine whether clients' narrative meaning
      making processes were associated with SGs in mental health. METHOD: 54
      psychotherapy clients completed the Systemic Therapy Inventory of Change (Pinsof
      et al., 2009) and wrote private narratives prior to beginning treatment and
      between every session for 12 assessment points over the course of psychotherapy
      for a variety of presenting problems. Clients' narratives were coded using
      existing systems (Adler, 2012; A. M. Hayes, Feldman, & Goldfried, 2006) to assess
      their content in eight themes: processing, avoidance, coherence, positive self,
      negative self, agency, hope, and hopelessness. RESULTS: The prevalence,
      magnitude, and timing of SGs in mental health observed in the present study were
      similar to those observed in prior research. Two narrative meaning-making
      processes-processing and coherence-were significantly associated with SGs in
      mental health. CONCLUSION: The present study significantly extends prior research
      on SGs, replicating the characteristics of these gains in routine clinical
      conditions with a measure of general functioning and identifying two narrative
      meaning-making processes that are associated with SGs in mental health.

PMID- 23875823
TI  - The effects of anatabine on non-invasive indicators of muscle damage: a
      randomized, double-blind, placebo-controlled, crossover study.
AB  - BACKGROUND: Anatabine (ANA), a minor tobacco alkaloid found in the Solanaceae
      family of plants, may exhibit anti-inflammatory activity, which may be useful to
      aid in recovery from exercise-induced muscle damage. The purpose of this study,
      therefore, was to examine the effects of ANA supplementation on the recovery of
      isometric strength and selected non-invasive indicators of muscle damage.
      METHODS: A double-blinded, placebo-controlled, crossover design was used to study
      eighteen men (mean +/- SD age = 22.2 +/- 3.1 yrs; body mass = 80.3 +/- 15.7 kg)
      who participated in two randomly-ordered conditions separated by a washout
      period. The ANA condition consisted of consuming 6-12 mg anatabine per day for 10
      days, while testing took place during days 7-10. The placebo (PLA) condition was
      identical except that the PLA supplement contained no ANA. Maximal voluntary
      isometric peak torque (PT) of the forearm flexors, arm circumference, hanging
      joint angle, and subjective pain ratings were measured before (PRE), immediately
      after (POST), and 24, 48, and 72 h after six sets of 10 maximal, eccentric
      isokinetic forearm flexion muscle actions. Resting heart rate and blood pressure
      were measured at PRE and 72 h in each condition. RESULTS: For PT, hanging joint
      angle, arm circumference, and subjective pain ratings, there were no condition x
      time (p > 0.05) interactions, there were no main effects for condition (p >
      0.05), but there were main effects for time (p < 0.001). There were no condition
      x time (p > 0.05) interactions and no main effects for condition (p > 0.05) or
      time (p > 0.05) for blood pressure or resting heart rate. CONCLUSIONS: ANA
      supplementation had no effect on the recovery of muscle strength, hanging joint
      angle, arm swelling, or subjective pain ratings after a bout of maximal eccentric
      exercise in the forearm flexors. Therefore, ANA may not be beneficial for those
      seeking to improve recovery from heavy eccentric exercise. Future studies should
      examine the effects of ANA on the pro-inflammatory cytokine responses to exercise
      induced muscle damage and the chronic low-grade inflammation observed in obese
      and elderly individuals.

PMID- 23875824
TI  - Infections and inflammatory bowel disease: challenges in Asia.
AB  - The diagnosis and management of inflammatory bowel disease (IBD) in Asia can be
      challenging as certain infections can mimic IBD and lead to a misdiagnosis.
      Colitis can be caused by bacterial infections, ileitis can result from Yersinia
      and Salmonella infections and ileocolonic ulcers can be seen in intestinal
      tuberculosis and amebiasis. In addition, cytomegalovirus and Clostridium
      difficile infection may mimic a flare of IBD and their presence is associated
      with an increased risk of colectomy and mortality. Because of the increasing use
      of corticosteroids, immunosuppressive drugs and biological agents the risk of
      opportunistic infection and the reactivation of latent infection including
      tuberculosis and hepatitis B, are also higher in IBD patients. Screening and
      prevention of infection, timely vaccination and the education of the patient is
      paramount before initiating immunosuppressive drugs. The role of the physician
      lies not only in the diagnosis and management of IBD but also in the ability to
      prevent, recognize and treat infections. 

PMID- 23875826
TI  - Introduction of President Eric S. Loker.

PMID- 23875825
TI  - Hypomethylation of long interspersed nuclear element-1 promoter is associated
      with poor outcomes for curative resected hepatocellular carcinoma.
AB  - BACKGROUND: Epigenetic alterations are well documented in hepatocarcinogenesis.
      However, hypomethylation of long interspersed nuclear element 1(LINE-1) promoter
      and its relationship with clinicopathological features in hepatocellular
      carcinoma(HCC) remain unknown. METHODS: The bisulfite-specific PCR and DNA
      sequencing analysis was performed to assess the methylation status of LINE-1
      promoter in a pilot cohort of 71 patients with HCC. Additionally,methylation
      levels of two hot CpG sites of LINE-1 promoter, site 7 and 18 were measured by
      real-time PCR and compared with clinicopathological parameters in a cohort of 172
      HCC. All the patients included were in BCLC stage A or B. RESULTS: Most patients
      with HCC (87.3%) showed hypomethylation of LINE-1 promoter compared with HBV
      related cirrhosis and normal controls (P < 0.001). The HCC patients with LINE-1
      promoter hypomethylation had a median tumour-free survival (TFS) and overall
      survival (OS)post-resection of 22.0 (95% CI: 13.3-30.7) months and 35.0 (95% CI:
      24.0-46.1) months, respectively, compared with 40 months and ~60 months for those
      with LINE-1 promoter hypermethylation (P < 0.05). Multivariate analyses showed
      that the hypomethylation level at CpG site 7 and 18 of LINE-1 promoter, along
      with tumour size and tumour differentiation, was independently associated with
      both TFS and OS for patients with HCC after resection. CONCLUSION: Promoter
      hypomethylation of LINE-1, especially at the CpG site 7 and 18, was associated
      with a poor prognosis in HCC.

PMID- 23875828
TI  - The bread dough stability improving effect of pyranose oxidase from trametes
      multicolor and glucose oxidase from Aspergillus niger: unraveling the molecular
      mechanism.
AB  - Glucose oxidase (GO) and pyranose oxidase (P2O) improve dough stability and bread
      quality. We here studied whether their mode of action resides in cross-linking of
      proteins and/or arabinoxylan (AX) molecules through the production of H2O2.
      Evidence for both was deduced from a decrease in extractability of protein and AX
      from dough made with P2O, GO, or H2O2, using sodium dodecyl sulfate containing
      buffer and water, respectively. The addition of H2O2, P2O, or GO to a glutathione
      solution sharply decreased its sulfhydryl (SH) content. P2O or GO can trigger
      protein cross-linking through the formation of disulfide (SS) bonds. As a result
      thereof, SH/SS interchange reactions between low molecular mass SH containing
      compounds and gluten proteins can be hampered. Furthermore, a decrease in the
      level of monomeric ferulic acid (FA) esterified to AX in dough points to a role
      of FA bridges in cross-linking of AX molecules. Our results indicate that the
      molecular mechanism of dough and bread improvement by P2O and GO resides in cross
      linking of gluten proteins and AX by formation of H2O2. They furthermore show
      that the extent of cross-linking upon addition of P2O or GO strongly depends on
      the concentration (and production rate) of H2O2. 

PMID- 23875827
TI  - Parent-reported mild head injury history and behavioural performance in children
      at 6 years.
AB  - OBJECTIVE: Mild head and brain injuries have gained increasing attention from
      health professionals and researchers. Little is known about mild injuries, which
      may not always be diagnosed or brought to medical attention. This study examines
      the associations between parent-reported history of mild head injury and
      behavioural problems in a large community-based sample of Chinese children.
      METHOD: Subjects included 725 children from China. Parents reported on children's
      head injury history and behaviour at age 6 years using the Chinese version of the
      Child Behavior Checklist. Mild head injury was defined as injury without loss of
      consciousness or hospitalization. Standardized T-scores were compared for each of
      the seven clinical sub-scales and three summary behavioural measures, adjusting
      for confounders. Logistic models were used to calculate odds ratios (ORs) between
      head injury and behavioural problems. RESULTS: Parents reported that 97 children
      (14%) had a single injury and 70 (10%) had multiple injuries. Compared to the
      controls, head-injured children had worse behavioural outcomes and a higher
      prevalence of behavioural problems. Multiple injuries were associated with higher
      risk of certain internalizing and externalizing problems. CONCLUSION: Mild head
      injuries, especially incurred repeatedly, may still be a significant risk for
      adverse behaviours in children.

PMID- 23875829
TI  - In vivo growth inhibition of sarcoma 180 by Kielmeyera rugosa Choisy
      (Calophyllaceae).
AB  - The plant Kielmeyera rugosa Choisy (family Calophyllaceae), popularly known as
      'pau-santo', is traditionally used in Brazilian folk medicine. Recently, the
      dichloromethane extract-dichloromethane partition from stems of K. rugosa (KR)
      has shown positive results in our cytotoxic screening programme. Therefore, the
      aim of this study was to validate the antitumour activity of KR on sarcoma 180
      tumour-bearing mice. KR showed antitumour activity with both administration
      routes: intraperitoneal (50 and 100 mg/kg/day) and oral (100 and 200 mg/kg/day).
      Tumour growth inhibition rates were 40.8-34.9% and 25.4-51.8% after
      intraperitoneal and oral administrations, respectively. Treatment with KR did not
      significantly affect body mass, macroscopy of the organs or blood leukocyte
      counts. In conclusion, KR exhibited an in vivo antitumour effect without
      substantial toxicity.

PMID- 23875830
TI  - Decline in lumbar extensor muscle strength the older adults: correlation with
      age, gender and spine morphology.
AB  - BACKGROUND: Muscle morphology, age and gender may be determinants of muscle
      strength in older adults. However, very few research studies have directly
      examined such correlation in the ageing spine. The aim of the study was to
      examine the correlation between lumbar extensor muscle strength, its muscle fibre
      angles, thoracolumbar curvature, age and gender in the older and younger adults.
      METHODS: Muscle fibre angles of lumbar extensor muscles, thoracolumbar curvature
      and lumbar extensor muscle strength were examined in 26 young (mean age 27.9, SD
      5.2) and 26 older (mean age 72.1, SD 5.9) participants. Pearson's correlation was
      employed to determine the association among lumbar extensor muscle fibre angle,
      thoracolumbar curvature, age, gender and lumbar extensor muscle strength.
      Multiple stepwise linear regression analysis was used to identify significant
      determinants of lumbar extensor muscle strength. RESULTS: The results
      demonstrated a significant correlation between lumbar extensor muscle strength,
      muscle fibre angle, age and gender. In the step wise regression analysis, both
      gender and age were identified as the most robust determinant for lumbar extensor
      muscle strength in older adults. However, gender was the only determinant of
      muscle strength in the young. CONCLUSION: These results suggest that the decline
      in the lumbar extensor muscle strength in older adults was more dependent on age
      when compared to younger adults.

PMID- 23875832
TI  - X-ray crystal structure of rac-[Ru(phen)2dppz]2+ with d(ATGCAT)2 shows enantiomer
      orientations and water ordering.
AB  - We report an atomic resolution X-ray crystal structure containing both
      enantiomers of rac-[Ru(phen)2dppz](2+) with the d(ATGCAT)2 DNA duplex (phen =
      phenanthroline; dppz = dipyridophenazine). The first example of any enantiomeric
      pair crystallized with a DNA duplex shows different orientations of the Lambda
      and Delta binding sites, separated by a clearly defined structured water
      monolayer. Job plots show that the same species is present in solution. Each
      enantiomer is bound at a TG/CA step and shows intercalation from the minor
      groove. One water molecule is directly located on one phenazine N atom in the
      Delta-enantiomer only. 

PMID- 23875831
TI  - The FLS (fatty liver Shionogi) mouse reveals local expressions of lipocalin-2,
      CXCL1 and CXCL9 in the liver with non-alcoholic steatohepatitis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) encompasses a wide spectrum
      of diseases, ranging from simple steatosis to nonalcoholic steatohepatitis
      (NASH), which carries a significant risk of progression to cirrhosis and
      hepatocellular carcinoma. Since NASH is a progressive but reversible condition,
      it is desirable to distinguish NASH from simple steatosis, and to treat NASH
      patients at an early stage. To establish appropriate diagnosis and therapy, the
      pathological mechanisms of the disease should be elucidated; however, these have
      not been fully clarified for both NASH and simple steatosis. This study aims to
      reveal the differences between simple steatosis and NASH. METHODS: This study
      used fatty liver Shionogi (FLS) mice as a NASH model, for comparison with dd
      Shionogi (DS) mice as a model of simple steatosis. Genome-wide gene expression
      analysis was performed using Affymetrix GeneChip Mouse Genome 430 2.0 Array,
      which contains 45101 probe sets for known and predicted genes. Quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) and
      immunohistochemistry were used to investigate gene expression changes and protein
      localizations. RESULTS: DNA microarray analysis of the liver transcriptomes and
      qRT-PCR of both types of mice revealed that LCN2, CXCL1 and CXCL9 mRNAs were
      overexpressed in FLS mouse livers. Immunohistochemistry showed that CXCL1 protein
      was mainly localized to steatotic hepatocytes. CXCL9 protein-expressing
      hepatocytes and sinusoidal endothelium were localized in some areas of
      inflammatory cell infiltration. Most interestingly, hepatocytes expressing LCN2,
      a kind of adipokine, were localized around almost all inflammatory cell clusters.
      Furthermore, there was a positive correlation between the number of LCN2-positive
      hepatocytes in the specimen and the number of inflammatory foci. CONCLUSIONS:
      Overexpression and distinct localization of LCN2, CXCL1 and CXCL9 in the liver of
      fatty liver Shionogi mice suggest significant roles of these proteins in the
      pathogenesis of NASH.

PMID- 23875833
TI  - Argon cluster ion source evaluation on lipid standards and rat brain tissue
      samples.
AB  - Argon cluster ion sources for sputtering and secondary ion mass spectrometry use
      projectiles consisting of several hundreds of atoms, accelerated to 10-20 keV,
      and deposit their kinetic energy within the top few nanometers of the surface.
      For organic materials, the sputtering yield is high removing material to similar
      depth. Consequently, the exposed new surface is relatively damage free. It has
      thus been demonstrated on model samples that it is now really possible to perform
      dual beam depth profiling experiments in organic materials with this new kind of
      ion source. Here, this possibility has been tested directly on tissue samples, 14
      MUm thick rat brain sections, allowing primary ion doses much larger than the so
      called static secondary ion mass spectrometry (SIMS) limit and demonstrating the
      possibility to enhance the sensitivity of time-of-flight (TOF)-SIMS biological
      imaging. However, the depth analyses have also shown some variations of the
      chemical composition as a function of depth, particularly for cholesterol, as
      well as some possible matrix effects due to the presence or absence of this
      compound. 

PMID- 23875834
TI  - Comparison of hematologic indices and markers of infection in umbilical cord and
      neonatal blood.
AB  - OBJECTIVE: Evaluation of a neonate for suspected early neonatal sepsis routinely
      includes blood tests such as complete blood count, C-reactive protein (CRP) and
      culture. In order to obviate the need for venepuncture, we prospectively compared
      these tests in paired samples from umbilical cord and peripheral venous blood
      drawn during the first hours after birth in both preterm and term infants.
      METHODS: Paired blood samples were studied from asymptomatic neonates with risk
      factors for early sepsis. Data were collected on maternal and neonatal factors
      that may have influenced the correlation between the tests. RESULTS: Three
      hundred fifty pairs of samples were studied. Significant correlation between
      umbilical cord and peripheral venous samples was found for white blood cell (WBC;
      r = 0.683) and platelets (PLT) (r = 0.54). Correlation for hemoglobin was lower
      (r = 0.36). No cases of early neonatal sepsis were detected. However,
      contamination rates were 12% in umbilical cord blood and 2.5% in peripheral
      venous blood cultures. WBC rose after birth and the 90th percentile rose from 22
      500 in umbilical cord blood to 29 700 in peripheral blood. CONCLUSIONS: Screening
      for sepsis with umbilical cord CBC may be useful provided normal ranges are
      adjusted accordingly.

PMID- 23875835
TI  - Influence of titanium on in vitro fibroblast-Porphyromonas gingivalis interaction
      in peri-implantitis.
AB  - AIM: Titanium wear particles have been found in peri-implant tissues, but their
      role in the pathogenesis of peri-implantitis remains unclear. We aimed to
      determine the in vitro inflammatory responses of peri-implant granulation tissue
      fibroblasts (PIGFs) to titanium particles alone and in the presence of viable
      Porphyromonas gingivalis. MATERIALS & METHODS: Peri-implant granulation tissue
      fibroblasts were challenged either with TiO2 particles, P. gingivalis or a
      combination of TiO2 particles and P. gingivalis. Gene expression and protein
      production of pro-inflammatory mediators by PIGFs were measured with PCR and
      ELISA, respectively. RESULTS: Higher doses of TiO2 were toxic to PIGFs and in sub
      toxic doses, TiO2 caused an increase in gene expression of tumour necrosis factor
      (TNF)-A and increased protein production of TNF-alpha, interleukin (IL)-6 and IL
      8. A challenge with P. gingivalis alone induced gene expression of TNF-A, IL
      1beta, IL-6 and IL-8. A combined challenge with TiO2 and P. gingivalis caused a
      stronger increase in gene expression of TNF-A and protein production of TNF-alpha
      and MCP-1 than P. gingivalis alone. CONCLUSIONS: TiO2 particles and P.
      gingivalis, individually, can induce pro-inflammatory responses in PIGFs.
      Furthermore, TiO2 particles and viable P. gingivalis further enhance gene
      expression and production of TNF-alpha by PIGFs. Therefore, Ti wear particles in
      the peri-implant tissues in combination with P. gingivalis infection may
      contribute to the pathogenesis of peri-implantitis by enhancing the inflammation
      in peri-implant tissues.

PMID- 23875836
TI  - Temporal sequence learning in healthy aging and amnestic mild cognitive
      impairment.
AB  - BACKGROUND/STUDY CONTEXT: Temporal sequence learning is a critical aspect of
      episodic memory that may be dependent on the temporal and frontal lobes. Because
      amnestic mild cognitive impairment (aMCI) and normal aging may result in changes
      within the temporal and frontal lobes, the present study investigated temporal
      sequence learning in patients with aMCI, cognitively normal older adults, and
      young adults. METHODS: On each trial of a temporal sequence task, circles
      appeared one at a time at the end of each arm of a computerized radial eight-arm
      maze. Participants were asked to reproduce the temporal sequence by placing
      numbered circles (1 to 8) on the arms of the eight-arm maze. Participants were
      presented with the same fixed sequence on each trial until the sequence was
      replicated without any errors, or until 15 trials were presented. RESULTS:
      Individuals with aMCI required significantly more trials to learn the temporal
      sequence compared with older adults (p < .05). Older adults required
      significantly more trials to learn the sequence than young adults (p < .05).
      Older adults and individuals with aMCI committed significantly more Trial 1
      errors (p < .05) than young adults; however, there were no significant
      differences between the aMCI and older adult groups on Trial 1. CONCLUSION: The
      results suggest that temporal sequence learning deficits are detectable in aMCI.
      These deficits may disrupt a number of cognitive processes, such as episodic
      memory, that are important for the execution of daily activities. The results
      suggest that although temporal sequence learning declines with normal aging, this
      decline is greater in individuals who have a diagnosis of aMCI and are at higher
      risk for developing Alzheimer's disease.

PMID- 23875837
TI  - Psychometric limitations of the mini-mental state examination among nondemented
      older adults: an evaluation of neurocognitive and magnetic resonance imaging
      correlates.
AB  - BACKGROUND/STUDY CONTEXT: Although many of the Mini-Mental State Examination's
      (MMSE) limitations are well accepted among geriatricians, neuropsychologists, and
      other interested clinicians and researchers, its continued use in
      psychometrically unsound ways suggests that additional investigation and
      dissemination of information are sorely needed. The authors aimed to describe the
      reliability and validity of the MMSE as a measure of cognitive function among
      healthy older adults. METHODS: The authors examined MMSE performance in 124
      stroke- and dementia-free, community-dwelling older adults (65% male; mean age =
      66.5 years). All participants were administered an extensive neuropsychological
      battery composed of measures of attention, executive function, memory, and
      visuospatial function. A subset of 99 participants also underwent magnetic
      resonance imaging (MRI). MMSE test-retest reliability was examined among 65
      participants who underwent repeat MMSE testing over an average interval of 83.2
      days. RESULTS: Spearman test-retest correlation for total MMSE scores was r S =
      .35 (p = .004), for Serial Sevens was r S = .40 (p = .001), and for Word Recall
      was r S = -.01 (p = .96). Total MMSE performance correlated significantly with a
      minority of neuropsychological tests and MRI-derived indices of white matter
      disease and brain atrophy. A subset of 17% of participants demonstrated
      inappropriate intrusion of MMSE Pentagon Copy during another test of visuospatial
      recall. CONCLUSIONS: Overall, MMSE scores exhibited ceiling effects, poor test
      retest reliability, limited sensitivity to subtle brain abnormalities, and a high
      rate of intrusion elsewhere in the neuropsychological battery. Individual MMSE
      items demonstrated poor construct validity. These qualities illustrate the
      serious limitations of the MMSE in detecting individual differences in cognitive
      function among healthy older adults.

PMID- 23875838
TI  - Extending the reach of an evidence-based theatrical intervention.
AB  - BACKGROUND/STUDY CONTEXT: In Experiment 1, the authors investigated whether they
      could train retirement home activity directors with no previous experience in
      theatre to successfully execute an evidence-based 4-week theatre-arts
      intervention. In Experiment 2, they investigated whether an outside professional
      acting teacher who received only minimal training via e-mail and telephone could
      successfully execute the same intervention heretofore only carried out by the
      actor/director/professor who devised it. METHODS: A total of 115 participants
      (ages 68-94) in four different retirement homes were taught theatre arts either
      by their in-house activity director who had no formal training in theatre or a
      professional acting teacher recruited through a local community college. The
      intervention consisted of twice-weekly 70-min lessons for 4 weeks. After random
      assignment to experimental or waiting-list control groups, participants were
      given pre- and posttests on both functional and cognitive measures. RESULTS:
      Experiment 1 showed that activity directors were able to run this intervention
      and achieve significant results on the 28-item functional measure (Observed Tasks
      of Daily Living, Revised [OTDL-R]) as measured by a mixed-design analysis of
      variance (ANOVA) and paired-sample t tests (p < .001), and on one cognitive
      measure, Means-End Problem-Solving (MEPS), as measured by a multivariate ANOVA
      (MANCOVA) and follow-up univariate ANOVAs. Experiment 2 (outside acting teacher)
      used the identical measures and revealed significant results on the OTDL-R (p =
      .002), word recall, MEPS, and verbal fluency (eta2(p) ranging from .28 to .59).
      CONCLUSIONS: This study addressed the feasibility of training multiple
      instructors of varying experience to administer this theatre-arts intervention.
      Previous iterations had all been administered by the professional
      actor/director/theatre professor who devised the program. These current results
      demonstrate that widespread administration of this short-term (4-week) evidence
      based intervention is feasible.

PMID- 23875839
TI  - Age-related sparing of parafoveal lexical processing.
AB  - BACKGROUND/STUDY CONTEXT: This study examined the role of increased adult age in
      the processing of lexical information presented in foveal and parafoveal areas of
      the retina (right and left visual fields). Previous research has shown that older
      adults are able to compensate for age-related changes though a highly practiced
      skill (Salthouse, 1984 , Journal of Experimental Psychology: General, 113, 345
      371). The authors examined if older adults would show a lexical-only parafoveal
      benefit. METHODS: Two experiments were conducted on both younger and older
      adults. In Experiment 1, participants completed a lexical decision task that
      presented words in the fovea and parafovea in both visual fields. In Experiment
      2, the task was a font discrimination task (nonlexical) with foveal and
      parafoveal presentation in both visual fields. RESULTS: In Experiment 1, the
      authors observed word frequency effects for both foveal and right parafoveal
      presentation locations. This effect was present for both older and younger
      adults. Experiment 2 was a font discrimination task and there was no right
      parafoveal advantage for older adults on this task, suggesting that this effect
      observed in Experiment 1 was lexical in nature due to the highly overlearned
      nature of word recognition. CONCLUSION: These results suggest that older adults
      may compensate for slower encoding time in reading by encoding text to the right
      of fixation more efficiently than younger adults. This suggests an asymmetrical
      change in the useful field of view that is lexical in nature.

PMID- 23875840
TI  - Workplace ageism: discovering hidden bias.
AB  - BACKGROUND/STUDY CONTEXT: Research largely shows no performance differences
      between older and younger employees, or that older workers even outperform
      younger employees, yet negative attitudes towards older workers can underpin
      discrimination. Unfortunately, traditional "explicit" techniques for assessing
      attitudes (i.e., self-report measures) have serious drawbacks. Therefore, using
      an approach that is novel to organizational contexts, the authors supplemented
      explicit with implicit (indirect) measures of attitudes towards older workers,
      and examined the malleability of both. METHODS: This research consists of two
      studies. The authors measured self-report (explicit) attitudes towards older and
      younger workers with a survey, and implicit attitudes with a reaction-time-based
      measure of implicit associations. In addition, to test whether attitudes were
      malleable, the authors measured attitudes before and after a mental imagery
      intervention, where the authors asked participants in the experimental group to
      imagine respected and valued older workers from their surroundings. RESULTS:
      Negative, stable implicit attitudes towards older workers emerged in two studies.
      Conversely, explicit attitudes showed no age bias and were more susceptible to
      change intervention, such that attitudes became more positive towards older
      workers following the experimental manipulation. CONCLUSION: This research
      demonstrates the unconscious nature of bias against older workers, and highlights
      the utility of implicit attitude measures in the context of the workplace. In the
      current era of aging workforce and skill shortages, implicit measures may be
      necessary to illuminate hidden workplace ageism.

PMID- 23875841
TI  - Older and (emotionally) smarter? Emotional intelligence as a mediator in the
      relationship between age and emotional labor strategies in service employees.
AB  - BACKGROUND/STUDY CONTEXT: The purpose of the current study was to investigate
      whether age was related to emotional labor strategies (surface and deep acting),
      and whether emotional intelligence partially explained this relationship.
      Additionally, employee well-being was examined as an outcome in this model.
      METHODS: A total of 519 participants (age 18-68), working in a variety of service
      occupations, participated in a cross-sectional survey study. Validated measures
      for emotional intelligence, emotional labor strategies, positive affectivity, and
      employee well-being were administered. RESULTS: A structural equation model
      supported the hypothesis that age was related positively to deep acting and
      negatively to surface acting, relationships partially mediated by emotional
      intelligence. Emotional labor strategy, in turn, affected well-being. CONCLUSION:
      Implications were discussed in employee selection and employee well-being,
      particularly in the customer service context. It is recommended that future
      research investigates how aging is related to emotional labor strategies in other
      occupations that have different emotional requirements (e.g., negative display
      rules).

PMID- 23875842
TI  - Quantitative plant resistance in cultivar mixtures: wheat yellow rust as a
      modeling case study.
AB  - Unlike qualitative plant resistance, which confers immunity to disease,
      quantitative resistance confers only a reduction in disease severity and this can
      be nonspecific. Consequently, the outcome of its deployment in cultivar mixtures
      is not easy to predict, as on the one hand it may reduce the heterogeneity of the
      mixture, but on the other it may induce competition between nonspecialized
      strains of the pathogen. To clarify the principles for the successful use of
      quantitative plant resistance in disease management, we built a parsimonious
      model describing the dynamics of competing pathogen strains spreading through a
      mixture of cultivars carrying nonspecific quantitative resistance. Using the
      parameterized model for a wheat-yellow rust system, we demonstrate that a more
      effective use of quantitative resistance in mixtures involves reinforcing the
      effect of the highly resistant cultivars rather than replacing them. We highlight
      the fact that the judicious deployment of the quantitative resistance in two- or
      three-component mixtures makes it possible to reduce disease severity using only
      small proportions of the highly resistant cultivar. Our results provide insights
      into the effects on pathogen dynamics of deploying quantitative plant resistance,
      and can provide guidance for choosing appropriate associations of cultivars and
      optimizing diversification strategies. 

PMID- 23875843
TI  - A wide-complex tachycardia after a medical test: what is the mechanism?

PMID- 23875845
TI  - Efficacy of omalizumab in chronic spontaneous urticaria refractory to
      conventional therapy: analysis of 110 patients in real-life practice.
AB  - OBJECTIVE: To collect data on the efficacy and safety of omalizumab in 110
      patients from 9 Spanish hospitals suffering from chronic spontaneous urticaria
      (CSU) refractory to conventional treatment. METHODS: A retrospective, descriptive
      analysis was performed, showing the data of 110 patients suffering from
      refractory CSU who received omalizumab as an off-label treatment in 9 Spanish
      hospitals from October 2009 to September 2012. RESULTS: Ninety (81.8%) patients
      exhibited a complete or significant response, 12 (10.9%) had partial response,
      and 8 (7.2%) showed no response. Sixty-six (60%) patients were able to stop all
      concomitant medications, remaining asymptomatic treated with omalizumab alone. No
      serious adverse events were reported. CONCLUSIONS: Omalizumab shows excellent
      efficacy and safety profile in a large series of CSU patients in real-life
      practice. This drug will contribute to settle the debt with CSU patients
      contributing to restore their quality of life.

PMID- 23875844
TI  - Evaluation of the diagnostic value of the first-trimester maternal serum high
      sensitivity C-reactive protein level for prediction of pre-eclampsia.
AB  - AIM: The purpose of the present study was to evaluate the diagnostic value of
      maternal serum high-sensitivity C-reactive protein (hs-CRP) measurement during
      the first trimester of pregnancy for predicting pre-eclampsia. MATERIAL AND
      METHODS: A prospective cohort study was performed on 394 pregnant women who were
      at the gestational age of 8-13 weeks. In all women, serum hs-CRP was measured by
      latex agglutination test. The women were then monitored to delivery. We compared
      the hs-CRP of the two groups, those with and without pre-eclampsia. We used the
      receiver-operator curve for finding the optimum cut-off points. RESULTS: Out of
      394 women, 42 cases (10.7%) were complicated by pre-eclampsia, of whom 23 women
      (56.1%) had severe pre-eclampsia. Mean serum hs-CRP of the pre-eclamptic group
      was higher than that of the normotensive group (7.06 +/- 2.6 mg/L vs 3.6 +/- 2.3
      mg/L, P = 0.001). The receiver-operator curve showed a significant difference
      between the under-curve zone for the hs-CRP level with the reference line. Serum
      hs-CRP of 4 mg/L showed sensitivity, specificity, positive predictive value,
      negative predictive value and diagnostic accuracy as 78.1%, 72.1%, 25%, 96.5% and
      72.8%, respectively. Hs-CRP of more than 7 mg/L was found in 26 (61.9%) cases of
      pre-eclampsia and 22 (6.25%) normotensive pregnancies, which showed a significant
      difference (P = 0.001, relative risk = 12.1, 95% confidence interval: 6.91
      21.15). Hs-CRP of more than 7 mg/L was found in 17 (73.91%) cases of severe pre
      eclampsia and 22 (6.25%) normotensive pregnancies, which showed a significant
      difference (P = 0.001, relative risk = 9.35, 95% confidence interval: 4.48
      19.52). CONCLUSION: Hs-CRP measurements during the first trimester of pregnancy
      are helpful in predicting pre-eclampsia.

PMID- 23875846
TI  - Microevolution from shock to adaptation revealed strategies improving ethanol
      tolerance and production in Thermoanaerobacter.
AB  - INTRODUCTION: The molecular links between shock-response and adaptation remain
      poorly understood, particularly for extremophiles. This has hindered rational
      engineering of solvent tolerance and correlated traits (e.g., productivity) in
      extremophiles. To untangle such molecular links, here we established a model that
      tracked the microevolution from shock to adaptation in thermophilic bacteria.
      METHOD: Temporal dynamics of genomes and transcriptomes was tracked for
      Thermoanaerobacter sp. X514 which under increasing exogenous ethanol evolved from
      ethanol-sensitive wild-type (Strain X) to tolerance of 2%- (XI) and eventually 6%
      ethanol (XII). Based on the reconstructed transcriptional network underlying
      stress tolerance, genetic engineering was employed to improve ethanol tolerance
      and production in Thermoanaerobacter. RESULTS: The spontaneous genome mutation
      rate (MUg) of Thermoanaerobacter sp. X514, calculated at 0.045, suggested a
      higher mutation rate in thermophile than previously thought. Transcriptomic
      comparison revealed that shock-response and adaptation were distinct in nature,
      whereas the transcriptomes of XII resembled those of the extendedly shocked X. To
      respond to ethanol shock, X employed fructose-specific phosphotransferase system
      (PTS), Arginine Deiminase (ADI) pathway, alcohol dehydrogenase (Adh) and a
      distinct mechanism of V-type ATPase. As an adaptation to exogenous ethanol, XI
      mobilized resistance-nodulation-cell division (RND) efflux system and Adh,
      whereas XII, which produced higher ethanol than XI, employed ECF-type ?24, an
      alcohol catabolism operon and phase-specific heat-shock proteins (Hsps),
      modulated hexose/pentose-transport operon structure and reinforced membrane
      rigidity. Exploiting these findings, we further showed that ethanol productivity
      and tolerance can be improved simultaneously by overexpressing adh or ?24 in X.
      CONCLUSION: Our work revealed thermophilic-bacteria specific features of adaptive
      evolution and demonstrated a rational strategy to engineer co-evolving industrial
      traits. As improvements of shock-response, stress tolerance and productivity have
      been crucial aims in industrial applications employing thermophiles, our findings
      should be valuable not just to the production of ethanol but also to a wide
      variety of biofuels and biochemicals.

PMID- 23875847
TI  - The relationship of serum cobalamin to methylmalonic acid concentrations and
      clinical variables in cats.
AB  - BACKGROUND: Serum cobalamin concentration [CBL] suggests CBL deficiency in cats
      but serum methylmalonic acid concentration [MMA] more accurately indicates CBL
      deficiency. OBJECTIVE: To examine the ability of [CBL] to predict CBL deficiency
      defined by increased [MMA], and relationships of [CBL] and [MMA] with select
      clinical and clinicopathological variables. ANIMALS: One hundred sixty-three
      client-owned cats with [CBL] measurements, 114 cats with simultaneous [MMA]
      measurements; 88 cats with medical information. METHODS: Prospectively collected
      [CBL] and [MMA] were compared using scatter plots, receiver operating
      characteristic and correlative analyses with historical [CBL] thresholds and
      those identified in the study. [CBL] and [MMA] were compared retrospectively to
      specific clinical and clinicopathological variables. RESULTS: [CBL] correlated
      negatively with [MMA] (tau = -0.334, P < .0001). [MMA] >= 1,343 nmol/L identified
      CBL deficiency. [CBL] = 209 pg/mL optimized sensitivity (0.51), specificity
      (0.96), PPV (0.89), and NPV (0.74) for detecting [MMA] >= 1,343 nmol/L.
      Prevalence of CBL deficiency was 42% (48/114) when defined by [MMA] >= 1,343
      nmol/L versus 23% (27/114) by [CBL] <= 209 pg/mL. Unexpectedly, 23 and 45% of 48
      cats with [MMA] >= 1,343 nmol/L had [CBL] > 900 pg/mL and 290 pg/mL (historical
      thresholds). [CBL] correlated with mean corpuscular volume (tau = -0.199, P =
      .013) and [MMA] with hematocrit (tau = -0.28, P = .006). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Cobalamin deficiency ([MMA] >= 1,343 nmol/L) occurred in 42% of cats
      and is predicted with high specificity by [CBL] <= 209 pg/mL. CBL status
      correlates with microcytosis and anemia. Discordance between [CBL] and [MMA]
      cautions against relying on any single marker for determining CBL status.

PMID- 23875848
TI  - Expanding our borders: Cultural Diversity and Ethnic Minority Psychology's
      special issue on immigration.
AB  - Introduces the current special issue of the journal, Cultural Diversity and
      Ethnic Minority Psychology. This special issue focuses on the topic of
      immigration and highlights the important within group differences often
      overlooked when immigrants are conceptualized as a homogeneous group. The
      articles in this journal consider a variety of microsystems, such as educational
      settings, ethnic and gay communities, and communities with anti-immigration laws.

PMID- 23875849
TI  - The importance of family factors and generation status: mental health service use
      among Latino and Asian Americans.
AB  - The present study utilized data from the National Latino and Asian American Study
      to examine ethnic and generational differences in family cultural conflict and
      family cohesion and how the effects of such family conflict and cohesion on
      lifetime service use vary by generation status for Latino Americans (n = 2,554)
      and Asian Americans (n = 2,095). Findings revealed that first-generation Asian
      Americans reported greater family cultural conflict than their Latino
      counterparts, but third-generation Latino Americans had higher family conflict
      than their Asian American counterparts. First-generation Latino and Asian
      Americans had the highest levels of family cohesion. Results from logistic
      regression analyses indicated that Latino Americans who reported higher family
      cultural conflict and lower family cohesion were more likely to use mental health
      services. For Asian Americans, family cultural conflict, but not family cohesion,
      was associated with service use. Relative to third-generation Asian Americans,
      second-generation Asian Americans with higher family cultural conflict were more
      likely to use mental health services. Given that cohesive familial bonds appear
      to discourage service use on the part of Latino Americans irrespective of
      generation status, further research is needed to ascertain the extent to which
      this tendency stems from greater reliance on family support as opposed to the
      stigma associated with mental health treatment. Mental health providers and
      treatment programs need to address the role of family cultural conflict in the
      lives of Asian Americans, particularly second generation, and Latino Americans
      across generations, because conflictual family ties may motivate help-seeking
      behaviors and reveal substantial underlying distress.

PMID- 23875850
TI  - "Hard to crack": experiences of community integration among first- and second
      generation Asian MSM in Canada.
AB  - Asians are the largest racial minority in Canada making up 11% of the population
      and represented over 60% of new immigrants between 2001 and 2006. We examined the
      experiences of community integration for first-generation (n = 27) and second
      generation (n = 22) Asian Canadian men who have sex with men (MSM) in their
      ethnic and gay communities. Through focus group interviews, we explored their
      level of connectedness and the level of discrimination they experienced in the
      two communities. Findings indicate that Asian MSM in general perceived their
      ethnic community as homophobic, stemming from a combination of seeing sex as
      taboo, stereotypes about being gay, and the affiliation with religion. Although
      the literature indicates that immigrants rely on the support of their ethnic
      communities, our finding suggest that this is not the case for Asian immigrant
      MSM, who in our sample reported feeling less connected compared to their second
      generation counterparts. For the gay community, our sample reported mixed
      experiences as some regarded it as welcoming, whereas others described it as
      racist. However, these experiences did not differ by generational status. Many
      were aware of explicit messages stating "No Asians" in dating contexts, while at
      the same time being aware that some older White men were interested in dating
      Asians exclusively. Barriers to integration in both communities may contribute to
      feelings of isolation. Theoretical implications are discussed.

PMID- 23875851
TI  - Perceived discrimination and depressive symptoms among immigrant-origin
      adolescents.
AB  - Although discrimination has been found to contribute to psychological distress
      among immigrant populations, there are few studies that have examined the
      relationship between racial and ethnic discrimination in the school setting among
      foreign-born immigrant and U.S.-born immigrant-origin adolescents. This study
      examined the relationship between perceived discrimination by adults and peers in
      the school setting and depressive symptoms in a sample (N = 95) of racial
      minority immigrant-origin adolescents (13 to 19 years of age) attending an urban
      high school. We examined the relation between perceived discrimination and
      depressive symptomology across gender and nativity status (foreign born vs. U.S.
      born), and the potential moderating role of ethnic identity and social support.
      Consistent with previous research, girls reported higher levels of depressive
      symptomology than boys, although the relationship between perceived
      discrimination and depressive symptoms was significant for both boys and girls.
      Perceived discrimination by adults and by peers at school was positively related
      to depressive symptoms for U.S.-born adolescents. For U.S.-born adolescents,
      ethnic identity mitigated the negative effects of perceived adult discrimination
      on depressive symptoms. However, ethnic identity did not moderate the
      relationship between perceived peer discrimination and depressive symptoms.
      Social support did not moderate the relationship between adult and peer
      discrimination and depressive symptoms for either foreign-born or U.S.-born
      adolescents. The findings support previous research concerning the immigrant
      paradox and highlight the importance of context in the relationship between
      perceived discrimination and mental health. Implications for future research and
      intervention are discussed.

PMID- 23875852
TI  - Day laborers' life satisfaction: the role of familismo, spirituality, work,
      health, and discrimination.
AB  - Limited research exists on day laborers' mental health. This study identifies
      relevant factors that influence the life satisfaction of 143 predominantly
      undocumented Latino male day laborers. Findings demonstrated the importance of
      familismo, spirituality, work satisfaction, perceived health, and perceived
      discrimination on life satisfaction. Given the deleterious impact discrimination
      can have on mental health, we examined whether perceived discrimination's role on
      life satisfaction would be buffered by familismo, spirituality, work
      satisfaction, and perceived health. Among these variable, spirituality and
      perceived health were identified as protective factors against the role of
      perceived discrimination on life satisfaction. Implications for research and
      practice with Latino male day laborers are discussed.

PMID- 23875853
TI  - "Why we stay": immigrants' motivations for remaining in communities impacted by
      anti-immigration policy.
AB  - Although restrictive immigration policy is intended to reduce incentives for
      unauthorized immigrants to remain in the United States, many immigrants remain in
      their U.S. community despite the anti-immigration climate surrounding them. This
      study explores motivations shaping immigrants' intentions to stay in Arizona
      after passage of Senate Bill 1070 in 2010, one of the most restrictive
      immigration policies in recent decades. We conducted three focus groups in a
      large metropolitan city in Arizona with Mexican immigrant parents (N = 25).
      Themes emerging from the focus groups described multiple and interlocking
      personal, family and community, and contemporary sociopolitical motivations to
      stay in their community, and suggest that some important motivating factors have
      evolved as a result of immigrants' changing environment. Implications for
      research and social policy reform are discussed.

PMID- 23875854
TI  - The colonial context of Filipino American immigrants' psychological experiences.
AB  - Because of the long colonial history of Filipinos and the highly Americanized
      climate of postcolonial Philippines, many scholars from various disciplines have
      speculated that colonialism and its legacies may play major roles in Filipino
      emigration to the United States. However, there are no known empirical studies in
      psychology that specifically investigate whether colonialism and its effects have
      influenced the psychological experiences of Filipino American immigrants prior to
      their arrival in the United States. Further, there is no existing empirical study
      that specifically investigates the extent to which colonialism and its legacies
      continue to influence Filipino American immigrants' mental health. Thus, using
      interviews (N = 6) and surveys (N = 219) with Filipino American immigrants, two
      studies found that colonialism and its consequences are important factors to
      consider when conceptualizing the psychological experiences of Filipino American
      immigrants. Specifically, the findings suggest that (a) Filipino American
      immigrants experienced ethnic and cultural denigration in the Philippines prior
      to their U.S. arrival, (b) ethnic and cultural denigration in the Philippines and
      in the United States may lead to the development of colonial mentality (CM), and
      (c) that CM may have negative mental health consequences among Filipino American
      immigrants. The two studies' findings suggest that the Filipino American
      immigration experience cannot be completely captured by the voluntary immigrant
      narrative, as they provide empirical support to the notion that the Filipino
      American immigration experience needs to be understood in the context of
      colonialism and its most insidious psychological legacy- CM.

PMID- 23875855
TI  - Rejection-(dis)identification and ethnic political engagement among first
      generation Latino immigrants to the United States.
AB  - Immigrants to the United States face rejection from other Americans on the basis
      of their ethnic group membership. Among members of ethnic minority groups who
      were born in the United States, rejection is tied to higher ethnic identification
      and less positive attitudes toward the national majority. Relatively little
      research has examined this relationship among first-generation immigrants (i.e.,
      people who were born in another country but who migrated to the United States) or
      has considered political engagement on behalf of one's ethnic group as an
      outcome. In this study we examined the relationship among ethnic-based rejection,
      ethnic and national identification, and ethnic political engagement among first
      generation Latino immigrants in the northeastern United States. We found that
      first-generation Latino immigrants who perceived ethnic-based rejection were less
      likely to identify with Americans and less likely to report willingness to engage
      politically on behalf of their ethnic group in the United States. Perceived
      rejection was not significantly associated with ethnic identification, which was
      not related to ethnic political engagement. The study demonstrates that ethnic
      based rejection has unique implications for identification and ethnic political
      engagement among first-generation Latino immigrants.

PMID- 23875856
TI  - "Reasonable suspicion" about tough immigration legislation: enforcing laws or
      ethnocentric exclusion?
AB  - We examined whether support for tough immigration legislation reflects identity
      neutral enforcement of law or identity-relevant defense of privilege.
      Participants read a fabricated news story in which law-enforcement personnel
      detained a person due to "reasonable suspicion" that he was an undocumented
      immigrant. We manipulated descriptions of the detainee so that he was either (a)
      an undocumented immigrant (both studies), (b) a documented immigrant (Study 1),
      or (c) a U.S. citizen (Study 2) of either Mexican or Canadian origin.
      Participants in both studies endorsed tougher punishment of an undocumented
      detainee and rated tough treatment as more fair when the detainee was of Mexican
      than Canadian origin (regardless of documentation status). Across both studies,
      the patterns of ethnocentric exclusion-harsher treatment toward Mexican
      immigrants than Canadian immigrants-were particularly pronounced among
      participants who defined American identity in terms of assimilation to
      Anglocentric cultural values (e.g., being able to speak English). Overall,
      results suggest that people may support tough measures to restrict immigration to
      defend against symbolic threats-especially threats that cultural "others" pose to
      Anglocentric understandings of American identity.

PMID- 23875857
TI  - The complexity and ambivalence of immigration attitudes: ambivalent stereotypes
      predict conflicting attitudes toward immigration policies.
AB  - Americans' conflicted attitudes toward immigrants and immigration has stymied
      immigration reform for decades. In this article, we explore the nuanced nature of
      stereotypes about immigrants and how they relate to ambivalent attitudes toward
      immigrant groups and the disparate array of immigration policies that affect
      them. Using item response theory and multiple regression analysis, we identified
      and related stereotypes of different immigrant groups to group-based and policy
      attitudes. Results demonstrate that ambivalent stereotypes mapped onto ambivalent
      group-based and immigration policy attitudes. Specifically, stereotypes that
      portray groups in positive or sympathetic ways predicted positive attitudes
      toward the group and more supportive attitudes toward policies that facilitate
      their immigration to the United States. Conversely, negative qualities predicted
      negative attitudes toward the same group and support for policies that prevent
      the group from immigrating. Results are discussed in light of current theory
      related to stereotype content, complementarity of stereotypes, and broader
      implications for immigration attitudes and policy.

PMID- 23875859
TI  - Synthetic glycopolypeptides as biomimetic analogues of natural glycoproteins.
AB  - Glycoproteins are naturally produced by protein glycosylation and are involved in
      a wide range of cellular functions. This Review aims to summarize the preparation
      of well-defined synthetic glycoproteins by using chemical routes as well as to
      highlight the preparation of ideal polymeric analogues of natural glycoproteins:
      glycopolypeptides. These macromolecules are simplified models of glycoproteins
      and are designed with the purpose of both mimicking the properties of natural
      glycoproteins as well as bringing innovative polymeric structures for materials
      science applications. 

PMID- 23875860
TI  - Bacterial contamination of needles used for intravitreal injections: comparison
      between 27-gauge and 30-gauge needles.
AB  - PURPOSE: To compare the contamination rate between 27-gauge and 30-guage needles
      used for intravitreal injection (IVT). METHODS: Patients undergoing IVT
      injections were enrolled prospectively. Injections were performed with 27- or 30
      gauge needles. All needle tips were collected and placed in brain-heart infusion
      broth. The contamination rates of needles were compared. RESULTS: A total of 109
      patients participated in the study and a total of 126 IVT injections were
      performed. Injections were performed by 27-gauge (49%) and 30-gauge (51%) needle.
      No patient developed endophthalmitis. The overall contamination rate of the used
      needles were 13% for 27-guage and 29% for 30-guage (p = 0.022). However, this
      difference was nonsignificant after Bonferroni's correction was applied. The most
      common bacteria isolated from the used needles are coagulase-negative
      Staphylococcus (CNS). CONCLUSION: The results suggest that the needle bore size
      seems not to be a risk factor for contamination during IVT injection.

PMID- 23875861
TI  - Land use in life cycle assessment: global characterization factors based on
      regional and global potential species extinction.
AB  - Land use is one of the main drivers of biodiversity loss. However, many life
      cycle assessment studies do not yet assess this effect because of the lack of
      reliable and operational methods. Here, we present an approach to modeling the
      impacts of regional land use on plants, mammals, birds, amphibians, and reptiles.
      Our global analysis calculates the total potential damage caused by all land uses
      within each WWF ecoregion and allocates this total damage to different types of
      land use per ecoregion. We use an adapted (matrix-calibrated) species-area
      relationship to model the potential regional extinction of nonendemic species
      caused by reversible land use and land use change impacts. The potential global
      extinction of endemic species is used to assess irreversible, permanent impacts.
      Model uncertainty is assessed using Monte Carlo simulations. The impacts of land
      use on biodiversity varied strongly across ecoregions, showing the highest values
      in regions where most natural habitat had been converted in the past. The
      approach is thus retrospective and was able to highlight the impacts in highly
      disturbed regions. However, we also illustrate how it can be applied to
      prospective assessments using scenarios of future land use. Uncertainties,
      modeling choices, and validity are discussed. 

PMID- 23875862
TI  - Risk factors for extensively drug-resistant tuberculosis: a review.
AB  - INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) is emerging as a
      global public health problem. Its treatment is more expensive and difficult, and
      the outcomes much severe. The identification of risk factors for XDR-TB is of
      paramount importance to design effective TB control strategies. OBJECTIVE: To
      review published articles on risk factors for XDR-TB. METHODS: We identified 249
      English articles on PubMed, and 182 were excluded by the abstract. The remaining
      articles were retrieved for full-text detailed evaluation by authors, and 27
      relevant articles were selected for final review. RESULTS: Some risk factors were
      consistently present, mainly previous TB treatment and its length. Other
      conditions often associated were immigration, alcoholism and HIV coinfection. Pre
      XDR-TB points to an increased risk of XDR-TB. CONCLUSION: The information
      regarding determinants of XDR-TB is relatively weak. However, special emphasis
      should be given to minimize the risks of TB retreatment to prevent the emergence
      of highly resistant TB.

PMID- 23875863
TI  - Fabrication, characterization and simulation of Omega-gate twin poly-Si FinFET
      nonvolatile memory.
AB  - This study proposed the twin poly-Si fin field-effect transistor (FinFET)
      nonvolatile memory with a structure that is composed of Omega-gate nanowires
      (NWs). Experimental results show that the NW device has superior memory
      characteristics because its Omega-gate structure provides a large memory window
      and high program/erase efficiency. With respect to endurance and retention, the
      memory window can be maintained at 3.5 V after 104 program and erase cycles, and
      after 10 years, the charge is 47.7% of its initial value. This investigation
      explores its feasibility in the future active matrix liquid crystal display
      system-on-panel and three-dimensional stacked flash memory applications. 

PMID- 23875864
TI  - Long-term working memory deficits after concussion: electrophysiological
      evidence.
AB  - BACKGROUND: Persistent complaints of lingering memory and concentration
      difficulties are common following a concussion, although the brain basis of these
      is unknown. Some suggest abnormalities can be found on the P300 event-related
      potential component, recorded using electroencephalography (EEG), despite
      unobservable cognitive impairments. OBJECTIVE: To examine the P300 and cognitive
      performance following a remote concussion during an n-back task that varies in
      working memory load. RESEARCH DESIGN: Seventeen participants with a remote
      concussion and 17 controls performed a visual n-back task in which working memory
      demands were systematically increased by manipulating cognitive load.
      Participants also completed neuropsychological and self-report measures. RESULTS:
      The concussion group showed a decrease in P300 amplitude compared to controls
      that was independent of working memory load on the n-back task. While no
      performance differences were observed between groups, P300 amplitude was
      negatively correlated with response times at higher loads in both groups.
      CONCLUSION: High functioning young adults with a remote concussion may have
      inefficient recruitment of processing resources for target identification,
      evident by the attenuated P300. The negative correlations between response time
      and P300 amplitude suggest that the time necessary to accurately respond to
      targets increases as the efficiency of allocating processing resources decreases
      during highly demanding working memory tasks.

PMID- 23875865
TI  - Something to smile about: the interrelationship between attractiveness and
      emotional expression.
AB  - Previous studies have suggested a link between the processing of the emotional
      expression of a face and how attractive it appears. In two experiments we
      investigated the interrelationship between attractiveness and happiness. In
      Experiment 1 we presented morphed faces varying in attractiveness and happiness
      and asked participants to choose the more attractive of two simultaneously
      presented faces. In the second experiment we used the same stimuli as in
      Experiment 1 and asked participants to choose the happier face. The results of
      Experiment 1 revealed that the evaluation of attractiveness is strongly
      influenced by the intensity of a smile expressed on a face: A happy facial
      expression could even compensate for relative unattractiveness. Conversely, the
      findings of Experiment 2 showed that facial attractiveness also influences the
      evaluation of happiness: It was easier to choose the happier of two faces if the
      happier face was also more attractive. We discuss the interrelationship of
      happiness and attractiveness with regard to evolutionary relevance of positive
      affective status and rewarding effects. 

PMID- 23875867
TI  - Mechanisms of DNA sensing on graphene oxide.
AB  - Adsorption of a fluorophore-labeled DNA probe by graphene oxide (GO) produces a
      sensor that gives fluorescence enhancement in the presence of its complementary
      DNA (cDNA). While many important analytical applications have been demonstrated,
      it remains unclear how DNA hybridization takes place in the presence of GO,
      hindering further rational improvement of sensor design. For the first time, we
      report a set of experimental evidence to reveal a new mechanism involving
      nonspecific probe displacement followed by hybridization in the solution phase.
      In addition, we show quantitatively that only a small portion of the added cDNA
      molecules undergo hybridization while most are adsorbed by GO to play the
      displacement role. Therefore, it is possible to improve signaling by raising the
      hybridization efficiency. A key innovation herein is using probes and cDNA with a
      significant difference in their adsorption energy by GO. This study offers
      important mechanistic insights into the GO/DNA system. At the same time, it
      provides simple experimental methods to study the biomolecular reaction dynamics
      and mechanism on a surface, which may be applied for many other biosensor
      systems. 

PMID- 23875866
TI  - One-year outcome of frailty indicators and activities of daily living following
      the randomised controlled trial: "Continuum of care for frail older people".
AB  - BACKGROUND: The intervention; "Continuum of Care for Frail Older People", was
      designed to create an integrated continuum of care from the hospital emergency
      department through the hospital and back to the older person's own home. The aim
      of this study is to evaluate the effects of the intervention on functional
      ability in terms of activities of daily living (ADL). METHODS: The study is a non
      blinded controlled trial with participants randomised to either the intervention
      group or a control group with follow-ups at three-, six- and 12 months. The
      intervention involved collaboration between a nurse with geriatric competence at
      the emergency department, the hospital wards and a multi-professional team for
      care and rehabilitation of the older people in the municipality with a case
      manager as the hub. Older people who sought care at the emergency department at
      Sahlgrenska University Hospital/Molndal and who were discharged to their own
      homes in the municipality of Molndal, Sweden were asked to participate. Inclusion
      criteria were age 80 and older or 65 to 79 with at least one chronic disease and
      dependent in at least one ADL. Analyses were made on the basis of the intention
      to-treat principle. Outcome measures were ADL independence and eight frailty
      indicators. These were analysed, using Chi-square and odds ratio (OR). RESULTS: A
      total of 161 participated in the study, 76 persons allocated to the control group
      and 85 to the intervention group were analysed throughout the study. There were
      no significant differences between the groups with regards to change in frailty
      compared to baseline at any follow-up. At both the three- and twelve-month follow
      ups the intervention group had doubled their odds for improved ADL independence
      compared to the control (OR 2.37, 95% CI; 1.20 - 4.68) and (2.04, 95% CI; 1.03 -
      4.06) respectively. At six months the intervention group had halved their odds
      for decreased ADL independence (OR 0.52, 95% CI; 0.27 - 0.98) compared to the
      control group. CONCLUSIONS: The intervention has the potential to reduce
      dependency in ADLs, a valuable benefit both for the individual and for society.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT01260493.

PMID- 23875868
TI  - Phytochemical pattern of Gentiana species of Appennino in central Italy.
AB  - The molecular pattern of two Gentiana species, G. dinarica and G. lutea, present
      in a protected area of Appennino Centrale in Italy, was examined. Results were
      compared with literature data, examining the differences between the two species.

PMID- 23875870
TI  - Solar UV exposure of seafarers along subtropical and tropical shipping routes.
AB  - Seafarers working on decks of vessels at low latitudes are exposed to extremely
      high solar UV radiation. Their risk of developing skin cancer may be enhanced.
      Solar erythemal UV irradiance and exposure were measured for the first time on
      merchant vessels going along typical international routes at low latitudes. The
      measurements taken at horizontal incidence on the observation deck, and on
      different parts of the seaman (head, shoulder, chest and back) doing typical
      outdoor work show the highest portion (40-80% of horizontal exposure) incident on
      the head. 2 years of measurements of solar UV and VIS/NIR irradiance taken on the
      mast top of the Research Vessel METEOR were added to the data base. Radiative
      transfer model calculations were performed along all the routes with satellite
      based input data of ozone and aerosol for clear sky health-effective radiation
      including vitamin D3 (VD3). Measured data show extremely high noontime UV index
      values up to 19 with clear sky, and up to 22 due to cloud scattering. Eight hours
      erythemal exposure values are more than double of typical midlatitude summer
      values. Based on the results, an algorithm is presented to derive a seafarer's
      personal erythemal exposure according to his/her personal record of sea service. 

PMID- 23875869
TI  - Effect of interleukin-1beta treatment on co-cultures of human meniscus cells and
      bone marrow mesenchymal stromal cells.
AB  - BACKGROUND: Interleukin-1beta (IL-1beta) is a major mediator of local
      inflammation present in injured joints. In this study, we aimed at comparing the
      effect of IL-1beta on engineered tissues from MCs, BMSCs and co-cultured MCs and
      BMSCs. METHODS: We compared the effect of IL-1beta in 3 groups: (1) MCs, (2)
      BMSCs and, (3) co-cultures of MCs and BMSCs. We selected 1 to 3 ratio of MCs to
      BMSCs for the co-cultures. Passage two (P2) human BMSCs were obtained from two
      donors. Human MCs were isolated from menisci of 4 donors. Mono-cultures of MCs
      and BMSCs, and co-cultures of MCs and BMSCs were cultured in chondrogenic medium
      with TGFbeta3, as cell pellets for 14 days. Thereafter, pellets were cultured for
      3 more days in same medium as before with or without IL-1beta (500 pg/ml).
      Pellets were assessed histologically, biochemically and by RT-PCR for gene
      expression of aggrecan, sox9, MMP-1, collagens I and II. Statistics was performed
      using one-way ANOVA with Tukey's post-tests. RESULTS: Co-cultured pellets were
      the most intensely stained with safranin O and collagen II. Co-cultured pellets
      had the highest expression of sox9, collagen I and II. IL-1beta treatment
      slightly reduced the GAG/DNA of co-cultured pellets but still exceeded the sum of
      the GAG/DNA from the proportion of MCs and BMSCs in the co-cultured pellets.
      After IL-1beta treatment, the expression of sox9, collagen I and II in co
      cultured pellets was higher compared to their expression in pure pellets. IL
      1beta induced MMP-1 expression in mono-cultures of MCs but not significantly in
      mono-cultures of BMSCs or in co-cultured pellets. IL-1beta induced MMP-13
      expression in mono-cultured pellets of BMSCs and in co-cultured pellets.
      CONCLUSIONS: Co-cultures of MCs and BMSCs resulted in a synergistic production of
      cartilaginous matrix compared to mono-cultures of MCs and BMSCs. IL-1beta did not
      abrogate the accumulated GAG matrix in co-cultures but mediated a decreased mRNA
      expression of aggrecan, collagen II and Sox9. These results strengthen the
      combinatorial use of primary MCs and BMSCs as a cell source for meniscus tissue
      engineering by demonstrating retention of fibrochondrogenic phenotype after
      exposure to IL-1beta.

PMID- 23875871
TI  - The histogenetic base of renal capsular-derived tumors.
AB  - Capsulomas comprise a category of very rare benign tumors derived from the renal
      capsule, the most encountered being myxomas and leiomyomas. To get more
      information on the histogenetic origin of these tumors, a comprehensive
      ultrastructural investigation on the human renal capsule has been done on kidney
      biopsy samples performed for nephropathologic diagnosis. The human renal capsule
      ultrastructure is similar to that of the mammalian renal capsule. There are two
      cellular layers: an inner layer made up of particular (immature) smooth muscle
      cells, and a second outer layer consisting of fibroblasts, collagen fibers,
      extracellular matrix, and telocyte-like cells. Two cases of leiomyomas of
      microscopic dimensions, situated beneath the capsule have been described. Data
      from the literature presenting the ultrastructure and perirenal location of
      myxomas support the affiliation of these capsulomas with the resident renal
      capsular cells. Based on ultrastructural studies, the authors demonstrate the
      presence of telocyte-like cells in the outer layer of the human renal capsule and
      propose distinct histogeneses for leiomyomas and for capsular myxomas as derived
      from the inner and outer capsular layers, respectively.

PMID- 23875872
TI  - Does low birth weight affect P-wave and QT dispersion in childhood?
AB  - BACKGROUND: The aim of our study is to investigate the effects of low birth
      weight (LBW) on atrial conduction and ventricular repolarization in children by
      using P-wave dispersion (Pw-d) and QT dispersion (QT-d) analyses. These effects
      have not yet been studied in detail in LBW children. METHODS: Fifty LBW children
      and 70 normal birth weight (NBW) children were enrolled in this cross-sectional
      controlled study. The Pw-d and QT-d of the LBW and NBW children were
      investigated. Independent Student's t-test, Mann-Whitney U test, and chi(2) test
      were performed to compare these two groups. Stepwise multiple regression analysis
      was performed to investigate whether there was a relationship between P-wave
      indices, QT derivatives, anthropometric and clinical features, and
      echocardiographic parameters. RESULTS: Age, gender, body mass index, waist
      circumferences, systolic and diastolic blood pressure, and echocardiographic
      measurements were similar between the LBW group and the NBW group (all P values >
      0.05). The following findings were recorded for the LBW and NBW groups,
      respectively: the Pw-d (30 [10-50] ms vs 30 [10-50] ms, P = 0.977), QT-d (20 [10
      50] ms vs 30 [15-50] ms, P = 0.561), and QTc-d (26 [14-54] ms vs 33 [17-62] ms, P
      = 0.866). No significant difference was found in Pw-d, QT-d, and QTc-d in
      comparison between the groups (all P values > 0.05). Pw-d was related to left
      atrial diameter and QTc-d was associated with left ventricle mass index even
      though they were within the normal range. CONCLUSION: Compared with the NBW
      group, no significant difference was found in both atrial conduction and
      ventricular repolarization features in LBW children.

PMID- 23875873
TI  - Clinical utility and cost of non-invasive prenatal testing.

PMID- 23875874
TI  - Anandamide modulates the neuroendocrine responses induced by extracellular volume
      expansion.
AB  - (1) The aim of the present study was to evaluate the effects of
      intracerebroventricular administration of anandamide (AEA), an inhibitor of fatty
      acid amide hydrolase activity (URB597) and a CB1 receptor (CB1 R) antagonist
      (AM251) on the homeostatic responses elicited by extracellular volume expansion
      (EVE) in male adult rats. (2) Pretreatment with AEA (100 ng/4 MUL) significantly
      reduced the effect of hypertonic (H-) EVE on plasma concentrations of prolactin
      (PRL), oxytocin (OT) and corticosterone, but not vasopressin (AVP).
      Administration of URB597 (20 MUg/5 MUL) alone significantly reduced PRL, OT, AVP
      and corticosterone in the H-EVE group. Conversely, URB597 and AEA had no
      significant effect on basal hormone concentrations. Pretreatment with AM251 (200
      ng/2 MUL) potentiated OT but did not change AVP plasma levels in the H-EVE group.
      (3) Hypertonic EVE significantly increased AVP and OT mRNA expression in the
      supraoptic nucleus (SON), an effect that was blunted in AEA-pretreated rats.
      Pretreatment with AEA did not change the percentage of vasopressinergic or
      oxytocinergic neurons colocalizing c-Fos in the SON, but increased nitrate
      concentrations in the median eminence of animals subjected to H-EVE. (4) The
      present data suggest that: (i) vasopressinergic and oxytocinergic neurons may be
      differentially affected by AEA; (ii) activation of CB1 R may restrain the
      response of the neurohypophyseal system (NHS) to EVE; (iii) the hypothalamic
      pituitary-adrenal axis, PRL and the NHS may still be sensitive to AEA after EVE,
      with these effects probably not dependent on AEA metabolism; and (iv) AEA and
      nitric oxide could interact in vivo as modulators to directly control stress
      induced responses.

PMID- 23875875
TI  - Left atrial diverticula in patients undergoing atrial fibrillation ablation:
      morphologic analysis and clinical impact.
AB  - INTRODUCTION: Left atrial diverticula (LAD) have been reported to be (1) at risk
      for intracavitary thrombosis and cardiac perforation during ablation and (2)
      sites of extrapulmonary vein foci. In atrial fibrillation (AF) ablation, their
      presence might undermine procedure safety and efficacy. This observational study
      evaluates the morphology and clinical impact of LAD in patients undergoing AF
      ablation. METHODS AND RESULTS: Consecutive patients undergoing computed
      tomography scan (Aquilion 64, Toshiba, Otawara, Japan) and AF ablation with
      imaging integration (CARTO 3 Merge, Biosense Webster, CA, USA) in our center were
      included. Morphologic analysis was performed by 2 independent radiologists.
      Ablation was obtained by irrigated radiofrequency energy (Navistar Thermocool or
      Thermocool SF, Biosense Webster). Out of 212 patients, 58 (27.3%) had LAD; 74.4%
      of LAD were located in the anterosuperomedial left atrium. In patients with and
      without LAD, the prevalence of prior cerebrovascular events was similarly low.
      The rate of major periprocedure complications did not differ significantly: 1.7%
      versus 2.6% (P = 1) in patients with and without LAD, respectively. However, 1
      case of cardiac perforation occurred during ablation in a diverticulum. During
      follow-up, survival free from arrhythmia recurrences was comparable in the 2
      groups. CONCLUSION: LAD are present in about one-fourth of patients undergoing AF
      ablation and, in general, they have no impact on its safety and efficacy.
      However, occasionally, radiofrequency energy delivery in a LAD can cause tissue
      overheating and perforation.

PMID- 23875876
TI  - Impact of autogenous concentrated bone marrow aspirate on bone regeneration after
      sinus floor augmentation with a bovine bone substitute--a split-mouth pilot
      study.
AB  - PURPOSE: Mesenchymal stem cells (MSC) with biomaterials have osteoinductive
      potential. The aim of this study was to evaluate early bone formation in
      xenogenic sinus grafts in a direct comparison with and without MSCs after 3 and 6
      months. Literature on bone formation in pure xenogenic graft materials after 3
      months in a human model is still lacking. MATERIALS AND METHODS: In a split-mouth
      design, seven patients with a bilateral highly atrophic posterior maxilla were
      included. The test side was grafted with MSCs from concentrated bone marrow
      aspirate admixed to the bone graft material. On the control side, pure bovine
      bone material was applied. Biopsies were taken navigated after 3 and 6 months.
      RESULTS: After 3 months, new bone formation in the control group was 11.8% (SD
      6.2%) and in the test group 7.4% (SD 4.1%). After 6 months, the control group
      showed 13.9% (SD 8.5%) of new bone and the test group 13.5% NB (SD 5.4%). The
      fraction of bovine bone material after 3 months was 42.6% (SD 3.5%) in the test
      group and 34.9% (SD 11.8%) in the control group. After 6 months, the biomaterial
      content was comparable at both sides (test 36.2%, SD 7.8%; control 39.5%, SD
      9.3%). CONCLUSIONS: There was no significant difference in new bone formation
      between the test and control group with n = 7. The results may be dominated by
      the high mineral content of the biomaterial but could nevertheless be valuable
      for meta-analysis in the future.

PMID- 23875877
TI  - Effect of polymer composition on rheological and degradation properties of
      temperature-responsive gelling systems composed of acyl-capped PCLA-PEG-PCLA.
AB  - In this study, the ability to modulate the rheological and degradation properties
      of temperature-responsive gelling systems composed of acyl-capped poly(epsilon
      caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(epsilon-caprolactone-co
      lactide) (PCLA-PEG-PCLA) triblock copolymers was investigated. Eight polymers
      with varying molecular weight of PCLA, caproyl/lactoyl ratio (CL/LA) and capped
      with either acetyl- or propionyl-groups were synthesized by ring-opening
      polymerization of L-lactide and epsilon-caprolactone in toluene using PEG as
      initiator and tin(II) 2-ethylhexanoate as catalyst, and subsequently reacted in
      solution with an excess of acyl chloride to yield fully acyl-capped PCLA-PEG
      PCLA. The microstructure of the polymers was determined by (1)H NMR, and the
      thermal properties and crystallinity of the polymers in dry state and in 25 wt %
      aqueous systems were studied by differential scanning calorimetry and X-ray
      diffraction. Rheological and degradation/dissolution properties of aqueous
      systems composed of the polymers in 25 wt % aqueous systems were studied. (1)H
      NMR analysis revealed that the monomer sequence in the PCLA blocks was not fully
      random, resulting in relatively long CL sequences, even though
      transesterification was demonstrated by the enrichment with lactoyl units and the
      presence of PEG-OH end groups. Except the most hydrophilic polymer composed of
      acetyl-capped PCLA1400-PEG1500-PCLA1400 having a CL/LA molar ratio of 2.5, the
      polymers at 25 wt % in buffer were sols below room temperature and transformed
      into gels between room temperature and 37  degrees C, which makes them suitable
      as temperature-responsive gelling systems for drug delivery. Over a period of
      weeks at 37  degrees C, the systems containing polymers with long CL sequences
      (~8 CL) and propionyl end-groups became semicrystalline as shown by X-ray
      diffraction analysis. Degradation of the gels by dissolution at 37  degrees C
      took 100-150 days for the amorphous gels and 250-300 days for the semicrystalline
      gels. In conclusion, this study shows that changes in the polymer composition
      allow an easy but significant modulation of rheological and degradation
      properties.

PMID- 23875879
TI  - Endovascular treatment of M2 dissecting aneurysm presenting with subarachnoid
      haemorrhage.
AB  - A 63-year-old woman presented with a ruptured dissecting aneurysm (DA) at the
      right M2 region of the angular branches. This report describes a rare case of
      middle cerebral artery DA presenting with a subarachnoid haemorrhage (SAH); the
      patient was successfully treated with endovascular internal trapping of the DA,
      without a bypass surgery.

PMID- 23875880
TI  - Intrasellar pituitary mucocele: diagnostic dilemma.
AB  - Isolated intrasellar pituitary mucocele following transsphenoidal sinus surgery
      is extremely rare. The clinical features resemble a pituitary tumor, therefore
      careful radiological interpretation is crucial to reach the correct diagnosis. We
      report a case of intrasellar mucocele who had transsphenoidal sinus surgery
      performed 15 years prior.

PMID- 23875878
TI  - Oxidants, antioxidants and mitochondrial function in non-proliferative diabetic
      retinopathy.
AB  - BACKGROUND: Diabetic retinopathy (DR) is a preventable cause of visual
      disability. The aims of the present study were to investigate levels and behavior
      oxidative stress markers and mitochondrial function in non-proliferative DR
      (NPDR) and to establish the correlation between the severity of NPDR and markers
      of oxidative stress and mitochondrial function. METHODS: In a transverse
      analysis, type 2 diabetes mellitus (T2DM) patients with mild, moderate and severe
      non-proliferative DR (NPDR) were evaluated for markers of oxidative stress (i.e.
      products of lipid peroxidation (LPO) and nitric oxide (NO) catabolites) and
      antioxidant activity (i.e. total antioxidant capacity (TAC), catalase, and
      glutathione peroxidase (GPx) activity of erythrocytes). Mitochondrial function
      was also determined as the fluidity of the submitochondrial particles of
      platelets and the hydrolytic activity of F0 /F1 -ATPase. RESULTS: Levels of LPO
      and NO were significantly increased in T2DM patients with severe NPDR (3.19 +/-
      0.05 MUmol/mL and 45.62 +/- 1.27 pmol/mL, respectively; P < 0.007 and P < 0.0001
      vs levels in health volunteers, respectively), suggesting the presence of
      oxidative stress. TAC had significant decrease levels with minimum peak in severe
      retinopathy with 7.98 +/- 0.48 mEq/mL (P < 0.0001). In contrast with TAC,
      erythrocyte catalase and GPx activity was increased in patients with severe NPDR
      (139.4 +/- 4.4 and 117.13 +/- 14.84 U/mg, respectively; P < 0.0001 vs healthy
      volunteers for both), suggesting an imbalance between oxidants and antioxidants.
      The fluidity of membrane submitochondrial particles decreased significantly in
      T2DM patients with mild, moderate, or severe NPDR compared with that in healthy
      volunteers (P < 0.0001 for all). Furthermore, there was a significant increase in
      the hydrolytic activity of the F0 /F1 -ATPase in T2DM patients with mild NPDR
      (265.07 +/- 29.55 nmol/PO4 ; P < 0.0001 vs healthy volunteers), suggesting
      increased catabolism. CONCLUSIONS: Patients with NPDR exhibit oxidative
      deregulation with decreased membrane fluidity of submitochondrial particles and
      increased systemic catabolism (mitochondrial dysfunction) with the potential for
      generalized systemic damage in T2DM.

PMID- 23875881
TI  - Diagnosis of primary cerebral lymphomas: possible value of PCR testing in
      equivocal cases requiring rebiopsy.
AB  - INTRODUCTION. Rebiopsy rates as high as 12% have been reported in previous
      studies of Primary Central Nervous System Lymphoma (PCNSL). This can lead to
      secondary operations, increasing risks of morbidity to the patient and costs for
      the NHS. Polymerase Chain Reaction (PCR) testing for clonality in haematological
      malignancies has been applied to cases of lymphoma outwith the central nervous
      system (CNS), but is less commonly used in the diagnosis of CNS lymphomas.
      Clonality in B- and T-cell populations may indicate the presence of malignancy.
      We aimed to identify factors to reduce the rebiopsy rate in PCNSL. METHODS. We
      examined a cohort of 102 suspected cerebral lymphoma cases biopsied at Frenchay
      Hospital, Bristol over a 10-year period (2000-2010). Clinical data, including
      age, sex, location, pre-biopsy steroid use, the need for rebiopsy and
      histological diagnosis, were collected. We retrospectively reviewed rebiopsied
      cases and they subsequently underwent PCR testing for clonality. RESULTS.
      Overall, 96/102 (94%) cases achieved a histological diagnosis after one or more
      biopsies. 81/96 (84%) of these were lymphomas involving the brain and 15/96 (16%)
      were spinal lymphomas. The majority of these were B-cell lymphomas (95/96 (99%)),
      with one case of peripheral T-cell lymphoma (1/96 (1%)). Due to insufficient
      histological evidence of PCNSL after the first biopsy, 9/102 (9%) of cases had
      required rebiopsy. In 7/9 (78%) of these cases, we undertook PCR testing for
      clonality on tissue from the first biopsy. We found 3/7 (43%) cases were
      monoclonal for B or T populations, raising the possibility of PCNSL. CONCLUSIONS.
      We recommend that all CNS lymphoproliferative lesions be assessed by
      haematopathologists, with the inclusion of PCR testing particularly in equivocal
      cases. This would reduce the number of patients going for rebiopsy and reduce the
      patient morbidity and costs for the NHS.

PMID- 23875882
TI  - Seven years of cranioplasty in a regional neurosurgical centre.
AB  - INTRODUCTION: In recent years craniectomy has been widely used in the management
      of traumatic brain injury and ischaemic stroke. The objective of this study was
      to evaluate the indications, techniques and outcomes for patients undergoing
      cranioplasty over a recent 7-year period in a geographically distinct population.
      MATERIALS AND METHODS: An observational study was performed retrospectively, with
      review of case records from 2004 to 2011. Demographic, clinical and outcome data
      were collected, and complications were classified as major and minor. A multi
      variant analysis was performed to identify patient and management factors that
      influenced outcome. RESULTS: Data were collected on a total of 87 cranioplasty
      patients with a median age of 42 and a mean follow-up time of 3 years and 10
      months. The main indications for craniectomy were trauma (46%), infection (19%)
      intracranial haemorrhage (15%), tumour (13%) and ischaemic stroke (6%). Eight
      percent of patients had a synchronous craniectomy and cranioplasty, 14% had
      cranioplasty within 3 months of craniectomy, 21% within 3-6 months, 35% within 6
      12 months, 14% over 1 year and 8% over 2 years later. The most frequently
      implanted cranioplasty material was titanium (53%), followed by autologous bone
      (26%) and acrylic (15%). Administration of prophylactic antibiotics was recorded
      in 97% of cases. Major complications occurred in 20% of patients, including 2
      deaths (2%), 5 extradural haemorrhages (6%) and 9 infections (10%). A further 10%
      of cases experienced minor or cosmetic complications. CONCLUSIONS: Cranioplasty
      is often considered as a low-risk procedure following craniectomy. In our cohort,
      a 20% risk of major complications, including death, was identified. These
      findings contribute to the literature, emphasising that cranioplasty is a high
      risk procedure. Whilst compelling reasons may guide the undertaking of
      craniectomy, it is essential that consideration is given to the significant
      subsequent risks of cranioplasty.

PMID- 23875884
TI  - A review on comparing two commonly used rabbit anti-thymocyte globulins as
      induction therapy in solid organ transplantation.
AB  - INTRODUCTION: Two rabbit anti-thymocyte globulins (ATGs) (ThymoglobulinTM and ATG
      Fresenius (ATG-F)TM) have been used commonly for induction immunosuppression and
      treatment of acute rejection in solid organ transplantation. Therefore,
      literature review on comparative efficacy and side-effect profile of them would
      be of clinical interest. AREAS COVERED: This review evaluated all comparative
      studies in English language, focusing on the solid organ transplant patients who
      received Thymoglobulin or ATG-F as induction therapy. This review concluded that
      compared to ATG-F, Thymoglobulin possibly provides better protection against
      acute rejection and improves patient and graft survival but may result in more
      cytomegalovirus infection and post-transplant malignancy. Thymoglobulin produced
      more leukocyte depletion with a greater delay to recover, while ATG-F had more
      reduction effects on platelet and erythrocyte counts with an increased need to
      erythropoiesis-stimulating agent. EXPERT OPINION: The benefits of induction
      therapy with ATGs must be weighed against the costs and post-transplant
      complications. It is suggest that there is no substantial clinical difference
      between these two rabbit ATGs and each may be considered as induction therapy for
      solid organ transplantation based on availability and drug cost. Of special
      importance is adding antiviral therapy to the treatment regimen of patients who
      receive ATGs as induction therapy.

PMID- 23875883
TI  - (99m)Tc-Galacto-RGD2: a novel 99mTc-labeled cyclic RGD peptide dimer useful for
      tumor imaging.
AB  - This study sought to evaluate [(99m)Tc(HYNIC-Galacto-RGD2)(tricine)(TPPTS)]
      ((99m)Tc-Galacto-RGD2: HYNIC = 6-hydrazinonicotinyl; Galacto-RGD2 = Glu[cyclo[Arg
      Gly-Asp-D-Phe-Lys(SAA-PEG2-(1,2,3-triazole)-1-yl-4-methylamide)]]2 (SAA = 7-amino
      L-glycero-L-galacto-2,6-anhydro-7-deoxyheptanamide, and PEG2 = 3,6-dioxaoctanoic
      acid); and TPPTS = trisodium triphenylphosphine-3,3',3"-trisulfonate) as a new
      radiotracer for tumor imaging. Galacto-RGD2 was prepared via the copper(I)
      catalyzed 1,3-dipolar azide-alkyne Huisgen cycloaddition. HYNIC-Galacto-RGD2 was
      prepared by reacting Galacto-RGD2 with sodium succinimidyl 6-(2-(2
      sulfonatobenzaldehyde)hydrazono)nicotinate (HYNIC-OSu) in the presence of
      diisopropylethylamine, and was evaluated for its integrin alphavbeta3 binding
      affinity against (125)I-echistatin bound to U87MG glioma cells. The IC50 value
      for HYNIC-Galacto-RGD2 was determined to be 20 +/- 2 nM. (99m)Tc-Galacto-RGD2 was
      prepared in high specific activity (~ 185 GBq/MUmol) and high radiochemical
      purity (>95%), and was evaluated in athymic nude mice bearing U87MG glioma
      xenografts for its tumor-targeting capability and biodistribution. The tumor
      uptake of (99m)Tc-Galacto-RGD2 was 10.30 +/- 1.67, 8.37 +/- 2.13, 6.86 +/- 1.33,
      and 5.61 +/- 1.52%ID/g at 5, 30, 60, and 120 min p.i., respectively, which was in
      agreement with high integrin alphavbeta3 expression on glioma cells and
      neovasculature. Its lower uptake in intestines, lungs, and spleen suggests that
      (99m)Tc-Galacto-RGD2 has advantages over (99m)Tc-3P-RGD2 ([(99m)Tc(HYNIC-3P
      RGD2)(tricine)(TPPTS)]: 3P-RGD2 = PEG4-E[PEG4-c(RGDfK)]2; PEG4 = 15-amino
      4,7,10,13-tetraoxapentadecanoic acid) for imaging tumors in the chest and
      abdominal regions. U87MG tumors were readily detected by SPECT and the tumor
      uptake of (99m)Tc-Galacto-RGD2 was integrin alphavbeta3-specific. (99m)Tc-Galacto
      RGD2 also had very high metabolic stability. On the basis of results from this
      study, it was concluded that (99m)Tc-Galacto-RGD2 is an excellent radiotracer for
      imaging integrin alphavbeta3-positive tumors and related metastases.

PMID- 23875885
TI  - Mentalising and social problem solving in adults with Asperger's syndrome.
AB  - INTRODUCTION: It is well established that autistic spectrum disorder is linked to
      difficulties with mentalising, but the ways in which this affects everyday
      behaviour is less well understood. This study explored the nature and extent of
      difficulties in everyday social functioning in adults with Asperger's syndrome
      (AS), since increased understanding can enhance the development of more effective
      intervention strategies. METHODS: Individuals with AS (n=21) were compared with
      healthy control participants (n=21) on three tests of social cognition: the
      Mentalistic Interpretation task, which assesses interpretation of sarcasm and
      actions; the Social Problem Fluency task, which assesses ability to generate
      problem solutions; and the Social Problem Resolution task, which assesses
      judgement in selecting problem solutions. RESULTS: Comprehension of both
      sarcastic remarks and actions was impaired in those with AS on the mentalistic
      interpretation task. Participants with AS showed difficulties in identifying the
      awkward elements of everyday social scenarios, and they were also impaired in
      generating problem solutions but not in judging alternative solutions on the
      social problem fluency and resolution tasks. CONCLUSIONS: These tasks potentially
      provide a means of profiling strengths and weaknesses in social processing, which
      in turn has implications for informing clinical evaluation and training.

PMID- 23875886
TI  - Bacterial profile and antimicrobial susceptibility pattern in septicemia
      suspected patients attending Gondar University Hospital, Northwest Ethiopia.
AB  - BACKGROUND: Bacterial blood stream infection constitutes a significant public
      health problem and it is an important cause of morbidity and mortality in
      hospitalized patients. The aim of this study was to assess the prevalence of
      bacterial isolates from septicemia suspected patients and their antimicrobial
      susceptibility pattern in Gondar University Hospital. METHODS: This laboratory
      based retrospective study of 390 blood culture and susceptibility tests was
      conducted in Bacteriology Laboratory of the University of Gondar Teaching
      Hospital. The samples were collected and processed following standard
      microbiological techniques as part of the routine clinical management of the
      patient. Antibiotic susceptibility testing was done on pure culture isolates
      employing disc-diffusion method for the commonly used antibiotics. The data were
      analyzed by using SPSS version 16 and the results were summarized by using tables
      and graphs. RESULTS: Out of 390 blood culture results, 71 (18.2%) were culture
      positive. The predominant bacteria isolated from blood culture were Coagulase
      negative staphylococci 30 (42.3%), followed by S. aureus 17 (23.9%) and
      Klebiesella spp 9 (12.9%), E. coli 5 (7.0%), Pseudomonas aeroginosa 4 (5.6%) and
      Salmonella spp. 3 (4.2%). The gram positive and gram negative bacteria
      constituted 49 (69%) and 22 (31%) of the culture isolates; respectively. The
      isolates showed high rates of resistance to most antibiotics tested. The range of
      resistance for Gram positive and Gram negative were from 23.5% - 58.8%, and 20%-
      100% respectively. CONCLUSIONS: In the present study most of the pathogens
      isolated from blood culture showed high rate of resistance to most commonly used
      antibiotics used to treat bacterial infections. Therefore, rational use of
      antibiotics should be practiced.

PMID- 23875887
TI  - A peptide-spectrum scoring system based on ion alignment, intensity, and pair
      probabilities.
AB  - Peppy, the proteogenomic/proteomic search software, employs a novel method for
      assessing the match quality between an MS/MS spectrum and a theorized peptide
      sequence. The scoring system uses three score factors calculated with binomial
      probabilities: the probability that a fragment ion will randomly align with a
      peptide ion, the probability that the aligning ions will be selected from subsets
      of the most intense peaks, and the probability that the intensities of fragment
      ions identified as y-ions are greater than those of their counterpart b-ions. The
      scores produced by the method act as global confidence scores, which facilitate
      the accurate comparison of results and the estimation of false discovery rates.
      Peppy has been integrated into the meta-search engine PepArML to produce
      meaningful comparisons with Mascot, MSGF+, OMSSA, X!Tandem, k-Score and s-Score.
      For two of the four data sets examined with the PepArML analysis, Peppy exceeded
      the accuracy performance of the other scoring systems. Peppy is available for
      download at http://geneffects.com/peppy . 

PMID- 23875888
TI  - Coordinated EV adoption: double-digit reductions in emissions and fuel use for
      $40/vehicle-year.
AB  - Adoption of electric vehicles (EVs) would affect the costs and sources of
      electricity and the United States efficiency requirements for conventional
      vehicles (CVs). We model EV adoption scenarios in each of six regions of the
      Eastern Interconnection, containing 70% of the United States population. We
      develop electricity system optimization models at the multidecade, day-ahead, and
      hour-ahead time scales, incorporating spatial wind energy modeling, endogenous
      modeling of CV efficiencies, projections for EV efficiencies, and projected CV
      and EV costs. We find two means to reduce total consumer expenditure (TCE): (i)
      controlling charge timing and (ii) unlinking the fuel economy regulations for CVs
      from EVs. Although EVs provide minimal direct GHG reductions, controlled charging
      provides load flexibility, lowering the cost of renewable electricity. Without
      EVs, a 33% renewable electricity standard (RES) would cost $193/vehicle-year more
      than the reference case (10% RES). Combining a 33% RES, EVs with controlled
      charging and unlinking would reduce combined electric- and vehicle-sector CO2
      emissions by 27% and reduce gasoline consumption by 59% for $40/vehicle-year more
      than the reference case. Coordinating EV adoption with adoption of controlled
      charging, unlinked fuel economy regulations, and renewable electricity standards
      would provide low-cost reductions in emissions and fuel usage. 

PMID- 23875889
TI  - Time courses and time-resolved spectra of firefly bioluminescence initiated by
      two methods of ATP injection and photolysis of caged ATP.
AB  - The time-dependent characteristics of firefly bioluminescence initiated by manual
      injection of adenosine triphosphate (ATP) into buffer solution containing
      luciferin (Ln), luciferase (Luc) and Mg(2+) were measured with a resolution of 10
      ms, and compared with those obtained by photolysis of caged ATP. The time course
      depends on pH; both rise and decay rates decrease when pH is lowered from 7.8 to
      6.8. In contrast, the parameter lambda in the kinetic formula related to
      diffusion of ATP is almost independent of pH. The pH dependence of the time
      course of bioluminescence can be explained by the same pH tendency as the rate of
      ATP binding at the active site of Luc. The time-resolved spectra can be
      decomposed into two Gaussian components with maxima at 2.2 and 2.0 eV. At pH 7.8,
      the band at 2.2 eV is more intense than that at 2.0 eV for all three
      concentration conditions. At lower pH, the band at 2.2 eV becomes weaker than
      that at 2.0 eV. The intensity ratio of the 2.0 and 2.2 eV bands is constant for
      duration time of 600 s for both injection and photolysis experiments, and the
      above conclusions are unaffected by the concentration ratio [Ln]/[Luc].

PMID- 23875890
TI  - Rapid "step capture" of holes in chloroform during pulse radiolysis.
AB  - The fundamental process of hole capture in solution was investigated following
      pulse radiolysis with polyfluorene and 4-cyano-4"-pentyl-p-terphenyl scavengers.
      Contrary to expectation, a large fraction of holes were captured in experimental
      time-resolution limited ~20 ps steps, by a process much faster than diffusion of
      the initially formed solvent molecular cation. At the highest concentrations,
      1.92 mM for a 52 unit long polyfluorene and 800 mM for 4-cyano-4"-pentyl-p
      terphenyl, 66% and 99%, respectively, of the initially formed holes were captured
      by 20 ps, with radiation chemical yield G = 1.2 * 10(-7) and 1.7 * 10(-7) mol J(
      1). The data can be explained by capture of presolvated holes, analogous to
      presolvated electrons, possibly possessing extended wave functions, high
      mobilities, or excess kinetic energy for the first few picoseconds after their
      creation. Such a process is not generally known in solution; however, the
      observed step capture as a function of solute concentration is shown to be well
      explained by this model. In addition to understanding the capture process in
      solution, the very large step yields formed in 20 ps will provide the ability to
      resolve subsequent hole transfer on the polymers with >2 orders of magnitude
      better time resolution than expected. 

PMID- 23875891
TI  - Vestibular asymmetry predicts falls among elderly patients with multi-sensory
      dizziness.
AB  - BACKGROUND: Dizziness is the most common symptom in elderly patients and has been
      identified as a risk factor for falls. While BPPV is the most common cause of
      dizziness among elderly, multisensory deficits is the second, with visual,
      vestibular and proprioceptive reduced function. Asymmetric vestibular function is
      overrepresented in elderly persons with hip fractures and wrist fractures and can
      be accessed for screening. METHODS: In this prospective study with one year
      observation period, 55 patients (41 women, 14 men), 65 to 90 years old (median
      80, interquartile range 11) with multisensory dizziness were included. RESULTS:
      Headshake test were pathologic in 24 patients, which substantially increased the
      risk of falls (OR 3.4). Thirteen of the 21 patients who had fallen (p = 0.03),
      and all 6 patients who sustained three falls or more (p = 0.04), had vestibular
      asymmetry. No other measure could predict the risk of falls (OR 0.55-1.71).
      CONCLUSION: Signs of vestibular asymmetry among elderly with multisensory
      dizziness could predict falls. Hence, it seems important to address fall
      prevention programs to such a group of patients. Simple bedside tests of
      vestibular asymmetry might be a possibility to screen for one risk factor for
      falls among elderly.

PMID- 23875892
TI  - Direct observation of CD4 T cell morphologies and their cross-sectional traction
      force derivation on quartz nanopillar substrates using focused ion beam
      technique.
AB  - Direct observations of the primary mouse CD4 T cell morphologies, e.g., cell
      adhesion and cell spreading by culturing CD4 T cells in a short period of
      incubation (e.g., 20 min) on streptavidin-functionalized quartz nanopillar arrays
      (QNPA) using a high-content scanning electron microscopy method were reported.
      Furthermore, we first demonstrated cross-sectional cell traction force
      distribution of surface-bound CD4 T cells on QNPA substrates by culturing the
      cells on top of the QNPA and further analysis in deflection of underlying QNPA
      via focused ion beam-assisted technique. 

PMID- 23875893
TI  - Conjunctival juvenile xanthogranuloma in a preschool child.

PMID- 23875894
TI  - Membranous glomerulopathy in renal allograft: an ultrastructural study of 17
      cases.
AB  - BACKGROUND: Membranous glomerulopathy is a common complication of renal
      allograft. However, its incidence and prognosis are not well defined, because an
      undetermined number of them pass undiagnosed under the generic epigraph of
      chronic allograft nephropathy. MATERIALS AND METHODS: To assess the diagnostic
      refinement supplied by electron microscopy to conventional light and
      immunofluorescence procedures the authors reviewed 17 cases of electron
      microscopy-confirmed membranous glomerulonephritis in kidney allograft. In
      addition, they searched for other features of graft injury, particularly lesions
      associated with alloimmune reaction, in order to evaluate the contribution of
      each lesion to the long-term outcome of the allograft. RESULTS: In 4 of the 17
      cases of their series the diagnosis of membranous glomerulopathy was made by
      electron microscopy. In addition, in 5 samples, lesions of chronic alloimmune
      rejection were present (in 4 cases the diagnosis was based on electron microscopy
      findings). At the end point of the study, 3 of the 5 patients with chronic
      alloimmune injury were in dialysis, 1 had died with functioning allograft, and
      the fifth suffered severe renal failure but was not in dialysis. On the other
      hand, 3 of the 12 patients without evidence of alloimmune injury had returned to
      the dialysis program. CONCLUSIONS: Electron microscopy is a useful tool in the
      assessment of renal allograft pathology and can provide additional morphological
      features of prognostic relevance.

PMID- 23875895
TI  - TNFalpha secretion of monocytes exposed to pulsed radiofrequency treatment: a
      possible working mechanism of PRF chronic pain management.
AB  - Pulsed radiofrequency treatment (PRF) is a promising new technique increasingly
      used in treatment of chronic pain. The molecular working mechanism of PRF is not
      exactly known and is currently being investigated. This study investigates a
      possible role of PRF-induced modulation of TNFalpha secretion by differentiated
      monocytes in chronic pain management. The results show no significant PRF-induced
      change in TNFalpha secretion of lipopolysaccharides (LPS)-stimulated monocytes.
      However, PRF does significantly increase TNFalpha secretion of differentiated
      monocytes that have not been stimulated with LPS. This may indicate a possible
      role of PRF treatment in increasing TNFalpha production of nonstimulated
      monocytes. More research is needed to determine whether this is truly a part of
      the working mechanism of PRF in chronic pain management and which other factors
      are involved. 

PMID- 23875896
TI  - Ecological implications of single and mixed nitrogen nutrition in Arabidopsis
      thaliana.
AB  - BACKGROUND: Ecologists recognize that plants capture nitrogen in many chemical
      forms that include amino acids. Access to multiple nitrogen types in plant
      communities has been argued to enhance plant performance, access to nitrogen and
      alter ecological interactions in ways that may promote species coexistence.
      However, data supporting these arguments have been limited. While it is known
      that plants uptake amino acids from soil, long term studies that link amino acid
      uptake to measures of plant performance and potential reproductive effort are not
      typically performed. Here, a series of experiments that link uptake of nitrate,
      glutamine or asparagine with lifetime reproductive effort in Arabidopsis thaliana
      are reported. Nitrogen was offered either singly or in mixture and at a variety
      of combinations. Traits related to reproductive output were measured, as was the
      preference for each type of nitrogen. RESULTS: When plants were supplied with a
      single nitrogen type at concentrations from 0.1-0.9 mM, the ranking of nitrogen
      types was nitrate > glutamine > asparagine in terms of the relative performance
      of plants. When plants were supplied with two types of nitrogen in mixture at
      ratios between 0.1:0.9-0.9:0.1 mM, again plants performed best when nitrate was
      present, and poorly when amino acids were mixed. Additionally, stable isotopes
      revealed that plants preferentially captured nitrogen types matching the
      hierarchy of nitrate > glutamine > asparagine. Comparing between the two
      experiments revealed that mixed nitrogen nutrition was a net cost to the plants.
      CONCLUSIONS: Plant performance on mixed nitrogen was less than half the
      performance on equal amounts of any single nitrogen type. We asked: why did A.
      thaliana capture amino acids when doing so resulted in a net cost? We argue that
      available data cannot yet answer this question, but hypothesize that access to
      lower quality forms of nitrogen may become important when plants compete.

PMID- 23875897
TI  - Hypoglycemic and antioxidant activities of paeonol and its beneficial effect on
      diabetic encephalopathy in streptozotocin-induced diabetic rats.
AB  - Diabetic encephalopathy (DE) is one of the severe complications in patients with
      diabetes mellitus. Paeonol, an active compound isolated from the root bark of
      Paeonia suffruticosa, has significant antidiabetic activity in vivo. However, its
      underlying beneficial effects on DE were unclear. In the present study, the
      protective activity of paeonol on DE was evaluated in streptozotocin (STZ)
      induced diabetic rats. Paeonol at 50 and 100 mg/kg significantly increased body
      weight and decreased blood glucose levels, glycosylated serum proteins, and serum
      advanced glycation end products (AGEs) levels. Immunohistochemistry assays and
      Western blot analysis revealed a significant decrease in expressions on receptor
      for advanced glycation end products (RAGE) and nuclear factor kappa B (NF-kappaB)
      in hippocampus and cerebral cortical neurons after paeonol treatment.
      Furthermore, paeonol significantly increased glutathione content and remarkedly
      decreased induced nitric oxide synthase activity in hippocampus tissue. Our
      findings indicated that paeonol could improve the pathological damage of DE in
      STZ-induced diabetic rats. It might be associated with the modulating
      AGEs/RAGE/NF-kappaB pathway. This study suggested that paeonol might be a
      promising candidate for the prevention and treatment of DE.

PMID- 23875898
TI  - North American Ginseng (Panax quinquefolius) prevents hyperglycemia and
      associated pancreatic abnormalities in diabetes.
AB  - North American ginseng (NAG) has received increasing attention as an alternative
      medicine for the treatment of diabetes. Extract of the NAG root has been reported
      to possess antidiabetic properties, but the underlying mechanisms for such
      effects have not been identified. Here we investigated the effects of NAG root
      extract on type 1 and 2 diabetes and the underlying mechanisms involved for such
      effects. Type 1 [C57BL/6 mice with streptozotocin (STZ)-induction] and type 2
      (db/db) diabetic models were examined. Groups of diabetic mice (both type 1 and
      2) were treated with alcoholic extract of the NAG root (200 mg/kg BW/day, oral
      gavage) for 1 or 2 months following onset of diabetes. Ginseng treatment
      significantly increased the body weight in type 1 diabetic animals in contrast to
      the type 2 model, where it caused diminution of body weight. Blood glucose and
      glycated hemoglobin levels diminished in the diabetic groups of both models with
      NAG treatment. Interestingly, plasma insulin and C-peptide levels were
      significantly increased in the STZ-diabetic mice, whereas they were reduced in
      the db/db mice following NAG treatment. Histological and morphometric analyses
      (islet/pancreas ratio) of the pancreas revealed an increase in the islet area
      following the treatment compared to both the untreated diabetic groups. These
      data indicate that NAG possibly causes regeneration of beta-cells resulting in
      enhanced insulin secretion. On the other hand, in type 2 diabetes, the additional
      effects of NAG on body weight might have also resulted in improved glucose
      control.

PMID- 23875899
TI  - Comparative protective effect of hawthorn berry hydroalcoholic extract,
      atorvastatin, and mesalamine on experimentally induced colitis in rats.
AB  - The protective effect of hydroalcoholic extract of hawthorn berries (HBE) on
      acetic acid (AA)-induced colitis in rats was investigated. Forty-two Wistar rats
      were divided into seven groups, including control and test groups (n=6). The
      control animals received saline, and the test animals were treated with saline
      (sham group), mesalamine (50 mg/kg; M group), atorvastatin (20 mg/kg; A group),
      HBE (100 mg/kg; H group), mesalamine and HBE (HM group), or atorvastatin plus HBE
      (HA group), 3 days before and a week after colitis induction. Colitis was induced
      by administration of 1 mL AA (4%) via a polyethylene catheter intrarectally. High
      performance liquid chromatography analyses showed that HBE contained 0.13% and
      0.5% oleanolic acid and ursolic acid, respectively. Elevated myeloperoxidase
      activity and lipid peroxidation were attenuated in the HA group. The H and HM
      groups showed marked reductions in colitis-induced decreases in total thiol
      molecules and body weight. The histopathological studies revealed that HBE
      decreased colitis-induced edema and infiltration of neutrophils. Our data suggest
      the anti-inflammatory and antioxidant effects of HBE and atorvastatin protect
      against AA-induced colitis. The anti-inflammatory effect of HBE may be
      attributable to its ability to decrease myeloperoxidase activity as a biomarker
      of neutrophil infiltration.

PMID- 23875901
TI  - Dietary antioxidant activities in different germplasms of Mucuna.
AB  - Mucuna pruriens, an underutilized native legume of South India has been reported
      to have high levels of L-Dopa, and used in the treatment of Parkinson's disease.
      Cellular damage arising from reactive oxygen and nitrogen species is said to
      cause neurodegenerative disorders. Antioxidants could assuage this oxidative
      damage of tissue directly and/or indirectly by enhancing natural defenses and
      also scavenging the free radicals. In this context, the antioxidative potential
      of different germplasm of Mucuna species was analyzed. Assays were performed to
      evaluate the enzymatic and nonenzymatic antioxidants in the extracts. Methanolic
      extracts of Mucuna (black germplasm) yielded high levels dietary antioxidants
      viz., flavonoids, alkaloids, saponins, steroids and phlobotannins qualitatively.
      Tannins, total phenols, flavanoids, and steroids accounted for 13.60+/-1.8 tannic
      acid equivalents, 58.47+/-3.19 gallic acid equivalents, 23.7+/-3.12 quercetin
      equivalents, and 20.3+/-1.0 mg per 100 mg beta-sitosterol equivalents,
      respectively. Percentage of scavenging activity against hydroxyl, superoxide
      anion, nitric oxide, and hydrogen peroxide radicals were 39.12%; 57.1%; 41.26%,
      and 25.68%, respectively. Reducing capacity (17.74%) was seen to concurrently
      increase with extract concentration. Catalase, glutathione reductase, and
      polyphenol oxidase activities were found to be 30.15; 26.6 and 42.5 MUmol/mg of
      protein, respectively. The methanolic extract yielded the most potent levels of
      dietary antioxidants and exhibited high free-radical-scavenging activity.

PMID- 23875900
TI  - Genes related to suppression of malignant phenotype induced by Maitake D-Fraction
      in breast cancer cells.
AB  - It is already known that the Maitake (D-Fraction) mushroom is involved in
      stimulating the immune system and activating certain cells that attack cancer,
      including macrophages, T-cells, and natural killer cells. According to the U.S.
      National Cancer Institute, polysaccharide complexes present in Maitake mushrooms
      appear to have significant anticancer activity. However, the exact molecular
      mechanism of the Maitake antitumoral effect is still unclear. Previously, we have
      reported that Maitake (D-Fraction) induces apoptosis in breast cancer cells by
      activation of BCL2-antagonist/killer 1 (BAK1) gene expression. At the present
      work, we are identifying which genes are responsible for the suppression of the
      tumoral phenotype mechanism induced by Maitake (D-Fraction) in breast cancer
      cells. Human breast cancer MCF-7 cells were treated with and without increased
      concentrations of Maitake D-Fraction (36, 91, 183, 367 MUg/mL) for 24 h. Total
      RNA were isolated and cDNA microarrays were hybridized containing 25,000 human
      genes. Employing the cDNA microarray analysis, we found that Maitake D-Fraction
      modified the expression of 4068 genes (2420 were upmodulated and 1648 were
      downmodulated) in MCF-7 breast cancer cells in a dose-dependent manner during 24
      h of treatment. The present data shows that Maitake D-Fraction suppresses the
      breast tumoral phenotype through a putative molecular mechanism modifying the
      expression of certain genes (such as IGFBP-7, ITGA2, ICAM3, SOD2, CAV-1, Cul-3,
      NRF2, Cycline E, ST7, and SPARC) that are involved in apoptosis stimulation,
      inhibition of cell growth and proliferation, cell cycle arrest, blocking
      migration and metastasis of tumoral cells, and inducing multidrug sensitivity.
      Altogether, these results suggest that Maitake D-Fraction could be a potential
      new target for breast cancer chemoprevention and treatment.

PMID- 23875902
TI  - The relative abundance of oxygen alkyl-related groups in aliphatic domains is
      involved in the main pharmacological-pleiotropic effects of humic acids.
AB  - Despite the rather common presence of humic acid (HA), our full knowledge of its
      biological effect is still lacking. In this article, we first performed a
      physicochemical characterization of several HAs, and next, we evaluated their
      ability to affect interleukin-2 secretion, antibody secretion, wound healing (an
      in vitro model using HaCaT cells), cancer growth (the Lewis lung carcinoma
      model), and protection against hepatotoxicity. In all tested reactions, HA showed
      significant stimulation on immune reactions, including suppression of cancer
      growth and inhibition of lipopolysaccharide-induced hepatotoxicity. These effects
      were dependent on its chemical properties. The pleiotropic effects of HA observed
      in this article suggest the possible role of these compounds in human nutrition.

PMID- 23875903
TI  - Ethanol extract of Lycopus lucidus elicits positive inotropic effect via
      activation of Ca2+ entry and Ca2+ release in beating rabbit atria.
AB  - Lycopus lucidus Turcz has been widely used as a traditional Oriental medicine
      (TOM) in Korea and China and prescribed for the enhancement of heart function.
      However, the precise effects have yet to be defined. The purpose of the present
      study was, therefore, to address whether the ethanol extract of Lycopus lucidus
      Turcz (ELT) has a positive inotropic effect. ELT-induced changes in atrial
      mechanical dynamics (pulse pressure, dp/dt, and stroke volume), and cAMP efflux
      were measured in perfused beating rabbit atria. Three active components,
      rosmarinic acid, betulinic acid, and oleanolic acid were identified in ELT by
      high performance liquid chromatography analysis. ELT increased atrial dynamics in
      a concentration-dependent manner without changes in atrial cAMP levels and cAMP
      efflux. The ELT-induced positive inotropic effect was blocked by inhibition of
      the L-type Ca(2+) channels and sarcoplasmic reticulum (SR). Inhibitors of beta
      adrenoceptors had no effect on the ELT-induced positive inotropic effect. The
      results suggest that ELT exerts a positive inotropic effect via activation of
      Ca(2+) entry through L-type Ca(2+) channel and Ca(2+) release from the SR in
      beating rabbit atria.

PMID- 23875904
TI  - Aqueous extracts of two varieties of ginger (Zingiber officinale) inhibit
      angiotensin I-converting enzyme, iron(II), and sodium nitroprusside-induced lipid
      peroxidation in the rat heart in vitro.
AB  - Ginger has reportedly been used in folk medicine for the management and
      prevention of hypertension and other cardiovascular diseases. Therefore, this
      study sought to investigate the inhibitory effect of aqueous extracts of two
      varieties of ginger on a key enzyme linked to hypertension (angiotensin I
      converting enzyme [ACE]), and on pro-oxidants [Fe(2+) and sodium nitroprusside
      (SNP)] which have been shown to induce lipid peroxidation in the rat's isolated
      heart in vitro. Aqueous extracts (0.05 mg/mL) of red ginger (Zingiber officinale
      var. Rubra) and white ginger (Zingiber officinale Roscoe) were prepared and the
      ability of the extracts to inhibit ACE along with Fe(2+)- and SNP-induced lipid
      peroxidation was determined in rat's heart in vitro. Results revealed that both
      extracts inhibited ACE in a dose-dependent manner (25-125 MUg/mL). However, red
      ginger extract (EC50=27.5 MUg/mL) had a significantly (P<.05) higher inhibitory
      effect on ACE than white ginger extract (EC50=87.0 MUg/mL). Furthermore,
      incubation of the rat's heart in the presence of Fe(2+) and SNP caused a
      significant increase (P<.05) in the malondialdehyde (MDA) content of the heart
      homogenates, while the introduction of the ginger extracts (78-313 MUg/mL) caused
      a dose-dependent decrease in the MDA content of the stressed heart homogenates.
      This suggests that the possible mechanism through which ginger exerts its
      antihypertensive properties may be through inhibition of ACE activity and
      prevention of lipid peroxidation in the heart. Furthermore, red ginger showed
      stronger inhibition of ACE than white ginger. Additionally, it should be noted
      that these protective properties of the ginger varieties could be attributed to
      their polyphenol contents.

PMID- 23875905
TI  - Effect of barley flour, crude cinnamon, and their combination on glycemia,
      dyslipidemia, and adipose tissue hormones in type 2 diabetic rats.
AB  - This study aimed to evaluate the effects of barley flour, crude cinnamon, and
      their combination on blood glucose, serum insulin, serum lipid profile, and serum
      adipose tissue hormones in streptozotocin-induced diabetic rats. Male Wistar rats
      (n=35) were divided into five groups: nondiabetic, diabetic, diabetic group fed
      5% cinnamon, diabetic group fed 30% barley, and diabetic group fed 5% cinnamon
      and 30% barley. Fasting blood glucose, insulin, lipid profile, adiponectin, and
      leptin were measured after 8 weeks. Blood glucose significantly decreased in all
      treated diabetic rats compared with the diabetic group. Serum insulin and high
      density lipoprotein significantly increased, while cholesterol, triglycerides,
      and low-density lipoprotein were significantly decreased after 8 weeks.
      Adiponectin significantly increased, while leptin significantly decreased with
      administration of either cinnamon, barley, or their combination. No significant
      differences were observed among the three treated groups on all parameters. A
      cinnamon and barley combination caused obvious improvement in insulin-positive
      cells of pancreatic tissue. In conclusion, consuming diets containing either
      cinnamon, barley, or their combination regulates blood glucose, lipid profile,
      and adipose tissue hormones in type 2 diabetic rats. The most effective treatment
      was the cinnamon and barley combination.

PMID- 23875906
TI  - Crude dietary polysaccharide fraction isolated from jackfruit enhances immune
      system activity in mice.
AB  - Crude polysaccharides (PSs) were isolated from the fruit pulp of jackfruit, and
      their chemical composition determined and evaluated for an immune regulatory
      activity in mice. The PSs were isolated from water extracts of jackfruit pulp
      (JFP) using the ethanol precipitation method. The resulting precipitates were
      further purified by dialysis and protein depletion by the Sevage method. The
      phenol-sulfuric method was used to determine the content of the PSs. The
      composition of PSs was determined by the Sephadex-G200 column chromatography and
      high-performance liquid chromatography methods. The thymus index and macrophage
      phagocytic function methods in mice were used to evaluate the immune regulatory
      activity of JFP-PSs. The JFP-PSs content in jackfruit was about 21% (w/w) and the
      yield of crude PSs was 3.91%. The single molecular mass weight PS was the main
      constituent of JFP-PSs. The major monosaccharide residues were rhamnose, glucose,
      galactose, and arabinose. The JFP-PSs enhanced the thymus weight index and the
      phagocytic rate after 30 days of subchronic p.o. administration to mice at 4.5
      mg/kg. The JFP contains single molecular PS and JFP-PS has immune-stimulating
      activities in mice. These data suggest that at least some of the traditional uses
      of JFP can be ascribed to its immunomodulatory effects.

PMID- 23875907
TI  - Variable procedural strategies adapted to anatomical characteristics in catheter
      ablation of the cavotricuspid isthmus using a preoperative multidetector computed
      tomography analysis.
AB  - OBJECTIVES: This study aimed to investigate the anatomical characteristics
      complicating cavotricuspid isthmus (CTI) ablation and the effectiveness of
      various procedural strategies. METHODS AND RESULTS: This study included 446
      consecutive patients (362 males; mean age 60.5 +/- 10.4 years) in whom CTI
      ablation was performed. A total of 80 consecutive patients were evaluated in a
      preliminary study. The anatomy of the CTI was evaluated by multidetector row
      computed tomography (MDCT) prior to the procedure. A multivariate logistic
      regression analysis revealed that the angle and mean wall thickness of the CTI, a
      concave CTI morphology, and a prominent Eustachian ridge, were associated with a
      difficult CTI ablation (P < 0.01). In the main study, 366 consecutive patients
      were divided into 2 groups: a modulation group (catheter inversion technique for
      a concave aspect, prominent Eustachian ridge, and steep angle of the CTI or
      increased output for a thicker CTI) and nonmodulation group (conventional
      strategy). The duration and total amount of radiofrequency energy delivered were
      significantly shorter and smaller in the modulation group than those in the
      nonmodulation group (162.2 +/- 153.5 vs 222.7 +/- 191.9 seconds, P < 0.01, and
      16,962.4 +/- 11,545.6 vs 24,908.5 +/- 22,804.2 J, P < 0.01, respectively). The
      recurrence rate of type 1 atrial flutter after the CTI ablation in the
      nonmodulation group was significantly higher than that in the modulation group
      (6.3 vs 1.7%, P = 0.02). CONCLUSION: Changing the procedural strategies by
      adaptating them to the anatomical characteristics improved the outcomes of the
      CTI ablation.

PMID- 23875909
TI  - Morphological evolution of carbon nanofibers encapsulating SnCo alloys and its
      effect on growth of the solid electrolyte interphase layer.
AB  - Two distinctive one-dimensional (1-D) carbon nanofibers (CNFs) encapsulating
      irregularly and homogeneously segregated SnCo nanoparticles were synthesized via
      electrospinning of polyvinylpyrrolidone (PVP) and polyacrylonitrile (PAN)
      polymers containing Sn-Co acetate precursors and subsequent calcination in
      reducing atmosphere. CNFs synthesized with PVP, which undergoes structural
      degradation of the polymer during carbonization processes, exhibited irregular
      segregation of heterogeneous alloy particles composed of SnCo, Co3Sn2, and SnO
      with a size distribution of 30-100 nm. Large and exposed multiphase SnCo
      particles in PVP-driven amorphous CNFs (SnCo/PVP-CNFs) kept decomposing liquid
      electrolyte and were partly detached from CNFs during cycling, leading to a
      capacity fading at the earlier cycles. The closer study of solid electrolyte
      interphase (SEI) layers formed on the CNFs reveals that the gradual growth of
      fiber radius due to continuous increment of SEI layer thickness led to capacity
      fading. In contrast, SnCo particles in PAN-driven CNFs (SnCo/PAN-CNFs) showed
      dramatically reduced crystallite sizes (<10 nm) of single phase SnCo
      nanoparticles which were entirely embedded in dense, semicrystalline, and highly
      conducting 1-D carbon matrix. The growth of SEI layer was limited and saturated
      during cycling. As a result, SnCo/PAN-CNFs showed much improved cyclability
      (97.9% capacity retention) and lower SEI layer thickness (86 nm) after 100 cycles
      compared to SnCo/PVP-CNFs (capacity retention, 71.9%; SEI layer thickness, 593
      nm). This work verifies that the thermal behavior of carbon precursor is highly
      responsible for the growth mechanism of SEI layer accompanied with particles
      detachment and cyclability of alloy particle embedded CNFs. 

PMID- 23875908
TI  - Ibutilide increases the variability and complexity of atrial fibrillation
      electrograms: antiarrhythmic insights using signal analyses.
AB  - INTRODUCTION: Intravenous ibutilide is used to convert atrial fibrillation (AF)
      to sinus rhythm (SR) due to its Class III antiarrhythmic mechanisms. However, the
      effects of ibutilide on local electrograms (EGMs) during AF have not been
      elucidated. METHODS AND RESULTS: We used EGM analysis techniques to characterize
      how ibutilide administration changes the frequency, morphology, and repeatability
      of AF EGM signals, thereby providing insight into ibutilide's antiarrhythmic
      mechanism of action. AF recordings were collected from 21 patients with AF, both
      before and after ibutilide administration. The effects of ibutilide on the
      following AF EGM parameters were assessed: (1) dominant frequency (DF), (2)
      variations in EGM amplitude and overall morphology, (3) repetition of EGM
      patterns, and (4) complexity of the AF frequency spectra. When comparing pre-
      versus post-ibutilide administration EGMs, DF decreased from 5.45 Hz to 4.02 Hz
      (P < 0.0001). There was an increase in the variability of both AF EGM amplitudes
      (P = 0.003) and overall AF EGM morphologies (P = 0.003). AF EGM pattern
      repetitiveness decreased (P = 0.01), and the AF frequency spectral profile
      manifested greater complexity (P = 0.02). CONCLUSIONS: Novel EGM signal analysis
      techniques reveal that ibutilide administration causes increased complexity in
      the atrial electrical activation pattern with decreasing rate. These findings may
      be explained by the progressive destabilization of higher frequency, more
      homogeneous primary drivers of AF over the course of ibutilide administration,
      and/or less uniform propagation of atrial activation, until AF maintenance
      becomes more difficult and either transforms to atrial tachycardia or terminates
      to SR.

PMID- 23875910
TI  - Genomic resources notes accepted 1 April 2013-31 May 2013.
AB  - This article documents the public availability of approximately 15 000
      polymorphic SNP loci for the bighorn sheep Ovis canadensis. 

PMID- 23875911
TI  - Keloid-like morphoea.

PMID- 23875913
TI  - Identification and isolation of non-polar compounds from the chloroform extract
      of Scutellaria ramosissima.
AB  - In the present study, chloroform extract obtained from aerial parts of
      Scutellaria ramosissima was phytochemically investigated. A non-polar fraction
      was obtained from the chloroform extract and the chemical composition of this
      fraction was identified by GC-MS. The major components of the non-polar fraction
      of S. ramosissima were determined as heneicosane (12.18%), palmitic acid
      (11.79%), acetovanillone (6.28%), 5,6-dihydroxy-7,8-dimethoxyflavone (31.87%),
      (9Z)-octadecenoic (oleic) acid (8.21%), stigmasterol (2.68%), beta-sitosterol
      (2.65%) and 5,2'-dihydroxy-6,7,8,6'-tetramethoxyflavone (2.13%). In addition, 5,6
      dihydroxy-7,8-dimethoxyflavone was isolated from the same fraction by PTLC. 

PMID- 23875912
TI  - DUSP 4 expression identifies a subset of colorectal cancer tumors that differ in
      MAPK activation, regardless of the genotype.
AB  - As dual-specificity phosphatase (DUSP) expression has been correlated to
      sensitivity to MEK inhibitors, DUSP expression levels may indicate activation of
      the mitogen-activated protein kinase (MAPK) pathway in many tumor types. In this
      study, we investigate if DUSP levels can indicate different levels of MAPK
      activation within colorectal cancer (CRC) patients. In three different CRC
      patient microarray datasets, we analyzed the expression of DUSP1. DUSP4 and DUSP6
      according to mutational status, their correlation with survival and their
      association with different clinical characteristics. DUSP4 was significantly
      differentially expressed between all mutational subgroups with the highest
      expression in BRAF mutated tumors. Moreover, high DUSP4 expression was associated
      with a worse overall survival and with clinical characteristics typical for BRAF
      mutant patients. The use of DUSP expression as a predictive biomarker towards
      MAPK targeted therapy in CRC patients needs further investigation.

PMID- 23875914
TI  - PHA recovery from biomass.
AB  - The recovery of polyhydroxyalkanoates (PHAs) from biomass, that is, from
      bacterial cells, is one of the major obstacles in the industrial production of
      these polyesters. Since PHAs are naturally synthesized as intracellular storage
      compounds for carbon and energy and are for this deposited in the cytoplasm of
      the bacterial cell, PHAs are more or less tightly linked with the entire biomass,
      and the polyesters must be released from the cells before their isolation and
      purification can be conducted. This additional step, that is, the release from
      the cells, is a major difference from most other biotechnological processes where
      the product occurs outside of the cells because it is secreted into the medium in
      a bioreactor or because it is synthesized in vitro in an enzyme reactor in a cell
      free system. This additional step contributes significantly to the overall costs
      of production. In this review we provide an overview about the different
      processes that result in the release of PHA from the cells, and we evaluate these
      processes with regard to the suitability at large scale in the industry. 

PMID- 23875915
TI  - Synthesis and characterization of novel plasmonic Ag/AgX-CNTs (X = Cl, Br, I)
      nanocomposite photocatalysts and synergetic degradation of organic pollutant
      under visible light.
AB  - A series of novel well-defined Ag/AgX (X = Cl, Br, I) loaded carbon nanotubes
      (CNTs) composite photocatalysts (Ag/AgX-CNTs) were fabricated for the first time
      via a facile ultrasonic assistant deposition-precipitation method at the room
      temperature (25 +/- 1  degrees C). X-ray diffraction, X-ray photoelectron
      spectroscopy, nitrogen adsorption-desorption analysis, scanning electron
      microscopy, and ultraviolet-visible light absorption spectra analysis were used
      to characterize the structure, morphology, and optical properties of the as
      prepared photocatalysts. Results confirmed the existence of the direct
      interfacial contact between Ag/AgX nanoparticles and CNTs, and Ag/AgX-CNTs
      nanocomposites exhibit superior absorbance in the visible light (VL) region owing
      to the surface plasmon resonance (SPR) of Ag nanoparticles. The fabricated
      composite photocatalysts were employed to remove 2,4,6-tribromophenol (TBP) in
      aqueous phase. A remarkably enhanced VL photocatalytic degradation efficiency of
      Ag/AgX-CNTs nanocomposites was observed when compared to that of pure AgX or
      CNTs. The photocatalytic activity enhancement of Ag/AgX-CNTs was due to the
      effective electron transfer from photoexcited AgX and plasmon-excited Ag(0)
      nanoparticles to CNTs. This can effectively decrease the recombination of
      electron-hole pairs, lead to a prolonged lifetime of the photoholes that promotes
      the degradation efficiency. 

PMID- 23875916
TI  - Clinical outcome of the chronic flexor tenosynovitis in the hand caused by non
      tuberculous mycobacterium treated by extensive tenosynovectomy and drugs.
AB  - Chronic flexor tenosynovitis in the hand caused by non-tuberculous mycobacterial
      (NTM) infection is uncommon. Although some authors have recommended combining
      surgical and drug therapy, there are few reports about the timing of drug
      administration after operation. The purpose of this retrospective study was to
      analyse the clinical outcome of the protocol, which consisted of extensive
      tenosynovectomy and drug therapy administered after culture results had been
      obtained. Four men and one woman were included. Average age was 57.4 years and
      average follow-up period was 46.7 months. Extensive tenosynovectomy was performed
      and surgical specimen was examined histopathologically and microbiologically.
      After a positive culture result had been obtained, three kinds of drugs were
      administered. Clinical outcome including infectious condition, range of motion,
      and grip strength was examined. All patients were immunocompetent and had no
      underlying disease. Three patients were diagnosed at first operation and two were
      diagnosed at second operation. The average period of drug therapy was 5.5 months.
      In four patients, infection resolved with combination therapy. In one patient
      with surgical treatment, only swelling remained. Osteomyelitis of the scaphoid
      was found in one patient to whom systemic steroid had been administered because
      of a negative culture result at first operation. For immunocompetent patients,
      flexor tenosynovitis in the hand caused by NTM was resolved with a combination of
      surgical and drug treatment. Drug treatment seemed to be essential after a
      reduction of the infectious lesion and the timing of administration was safe
      enough to resolve in four patients.

PMID- 23875917
TI  - Contact lenses as a platform for ocular drug delivery.
AB  - INTRODUCTION: Most ophthalmic drugs are delivered through eye drops even though
      only about 1 - 5% of the drug reaches the target tissue and the patient
      compliance is not good. Drug-eluting contact lenses could significantly increase
      bioavailability, reduce side effects and improve patient compliance. AREAS
      COVERED: Recent research on drug-eluting contact lenses has focused on increasing
      the release duration through molecular imprinting, dispersion of barriers or
      nanoparticles, increasing drug binding to the polymer, sandwiching a PLGA
      (poly[lactic-co-glycolic acid]) layer in a lens and developing novel materials.
      This review covers all these studies with a specific focus on the transport
      mechanisms and advantages and disadvantages of each approach. EXPERT OPINION: The
      main reason for prior failures was the short duration of release from the lenses.
      The new technologies can provide extended drug release for hours to days. The in
      vivo animal and clinical studies have proven the safety and efficacy of drug
      eluting contact lenses, while showing considerable improvements compared to eye
      drops. The future appears to be promising but several challenges remain such as
      processing and storage issues, regulatory hurdles, high costs of clinical
      studies, potential lack of acceptance by the elderly, etc.

PMID- 23875918
TI  - Nectar quality perception by honey bees (Apis mellifera ligustica).
AB  - In exploring how foragers perceive rewards, we often find that well-motivated
      individuals are not too choosy and unmotivated individuals are unreliable and
      inconsistent. Nevertheless, when given a choice we see that individuals can
      clearly distinguish between rewards. Here we develop the logic of using responses
      to two-choice problems as a derivative function of perceived reward, and utilize
      this model to examine honey bee perception of nectar quality. Measuring the
      derivative allows us to deduce the perceived reward function. The derivative
      function of the perceived reward equation gives the rate of change of the reward
      perceived for each reward value. This approach depends on presenting free-flying
      foragers with a series of two different rewards presented simultaneously (i.e.,
      two-choice, binomial tests). We also examine how honey bees integrate information
      from a range of reward qualities to formulate a functional response. Results
      suggest that honey bees overestimate higher quality rewards and that direct
      comparison is an important step in the integration of information from a range of
      rewards.

PMID- 23875919
TI  - Where is the "meta" in animal metacognition?
AB  - Apes, dolphins, and some monkeys seem to have metacognitive abilities: They can
      accurately evaluate the likelihood that their response in cognitive task was (or
      will be) correct. These certainty judgments are seen as significant because they
      imply that animals can evaluate internal cognitive states, which may entail
      meaningful self-reflection. But little research has investigated what is being
      reflected upon: Researchers have assumed that when animals make metacognitive
      judgments they evaluate internal memory strength. Yet decades of research have
      demonstrated that humans cannot directly evaluate internal memory strength.
      Instead, they make certainty judgments by drawing inferences from cues they can
      evaluate, such as familiarity and ease of processing. It seems likely that
      animals do the same, but this hypothesis has not been tested. I suggest two
      strategies for investigating the internal cues that underlie animal metacognitive
      judgments. It is possible that animals, like humans, are capable of making
      certainty judgments based on internal cues without awareness or meaningful self
      reflection.

PMID- 23875920
TI  - Object permanence in the Goffin cockatoo (Cacatua goffini).
AB  - The ability to represent hidden objects plays an important role in the survival
      of many species. In order to provide an inclusive synopsis of the current
      benchmark tasks used to test object permanence in animals for a psittacine
      representative, we tested eight Goffin cockatoos (Cacatua goffini) on Stages 3-6
      of Piagetian object permanence as well as derivations of spatial transposition,
      rotation, and translocation tasks. Subjects instantly solved visible displacement
      3b and 4a but showed an extended plateau for solving Stage 5a at a very late age
      (10 months). Subjects readily solved most invisible displacement tasks including
      double hidings and four angles (90 degrees , 180 degrees , 270 degrees , and 360
      degrees ) of rotation and translocations at high performance levels, although
      Piagetian Stage 6 invisible displacement tasks caused more difficulties for the
      animals than transposition, rotations, and translocation tasks.

PMID- 23875921
TI  - Dogs (Canis familiaris) can learn to attend to connectivity in string pulling
      tasks.
AB  - String pulling tasks are commonly used to investigate recognition of means-end
      connections. Previous studies suggested that dogs base their choice on proximity
      rather than connectivity (Osthaus, Lea, & Slater, 2005), nonetheless, dogs
      performed successfully in the related support problem (Range, Hentrup, & Viranyi,
      2011). To reinvestigate dogs' means-end understanding, we tested 34 Border
      collies in string pulling tasks in which the proximity of the reward to the
      connected string's end was varied. First, subjects were presented with a four
      string task (four parallel perpendicular strings, one baited, with the reward in
      line with the correct string's end). Dogs that performed above chance in this
      task were tested with a curved string task, involving one straight and one curved
      string. When the reward was attached to the curved string, it was equidistant
      from both strings' ends so that choosing by proximity was not possible. Although
      group level performance was significantly above chance, only three of 20 dogs met
      criterion individually, of which one dog subsequently solved a broken string task
      upon its first presentation. However, the dogs seemed to be unable to overcome
      their proximity bias in a parallel diagonal string task where proximity of the
      unconnected string's end to the reward was misleading. We conclude that although
      dogs may not demonstrate means-end understanding spontaneously, some can learn to
      pay attention to connectivity when proximity is not a confounding factor. This
      study supports the notion that animals may apply several alternative strategies
      to solve physical problems, which are influenced by the test-setup.

PMID- 23875922
TI  - Interval timing behavior in Pallas's long-tongued bat (Glossophaga soricina).
AB  - Timing behavior in animals and its underlying mechanisms have been investigated
      extensively in the peak procedure, a variant of fixed interval procedures. In
      such experiments, individuals typically start responding with high frequency
      after an initial inactive time interval and continue their responses after peak
      time if rewards are omitted. This begs the so far unexplored question as to how
      timing behavior is influenced when such continuous responses are suppressed.
      Here, we present results from a nectar-feeding bat species, Glossophaga soricina,
      that was tested in a modified version of the peak procedure at three fixed time
      intervals (5 s, 11 s, 20 s). In contrast to standard peak procedures we imposed
      metabolic costs on individual responses which effectively suppressed trains of
      rapid responses during trials. Under this manipulation, bats' aggregated
      responses showed clear peaks around the peak time in the 5-s and 11-s schedules.
      Bats' responses in the 20-s schedule, however, did not peak around the fixed
      interval time. Crucially, an analysis of time intervals between successive
      revisits in all schedules revealed that bats revisited feeders at accurately
      timed intervals in all three conditions. The individual within trial behavioral
      responses showed clear oscillatory patterns throughout nonrewarded trials. These
      findings follow predictions from mechanistic timing models, like the striatal
      beat frequency model, and are discussed with regard to these models.

PMID- 23875923
TI  - Early infantile onset of atypical hemolytic-uremic syndrome is caused by
      recessive mutations in DGKE.

PMID- 23875924
TI  - FTDR 2.0: a tool to achieve sub-ppm level recalibrated accuracy in routine LC-MS
      analysis.
AB  - Advances in proteomics research involve the use of high-precision and high
      resolution mass spectrometry instruments. Although hardware improvements are the
      main impetus for the acquisition of high-quality data, enhancements in software
      tools are also needed. In this study, recalibration was verified as an important
      way to improve data accuracy. A new version tool, known as FTDR 2.0, was
      developed to recalibrate the mass-to-charge ratio error of most observed parent
      ions to the sub part per million level in routine experiments. First, many new
      parameters were introduced and screened as features online to reduce systematic
      error and to adapt to various data sets. Second, a support vector regression
      model was trained to characterize the complex nonlinear maps from features to
      mass-to-charge ratio measurement errors. Third, a specific mass-to-charge ratio
      error tolerance for each parent ion was estimated by considering the impact of
      signal intensity. FTDR 2.0 is a user-friendly tool that supports most commonly
      used data standards and formats. A C++ library and the source code are provided
      to support the redevelopment and integration into other mass spectrometry data
      processing tools. The performance of FTDR 2.0 was verified using several
      experimental data sets from different research programs. Recalibration with FTDR
      2.0 has been proved to improve the peptide identification in qualitative,
      quantitative, and post-translational modification analyses. 

PMID- 23875926
TI  - Surgical and obstetric outcomes of laparoscopic management for women with
      heterotopic pregnancy.
AB  - AIM: The aim of this study was to investigate the obstetric outcomes and clinical
      efficacy of laparoscopic surgery for women with heterotopic pregnancy. MATERIAL
      AND METHODS: We conducted a retrospective study of women who had undergone
      laparoscopic surgery for heterotopic pregnancy. The primary outcome was the
      feasibility of laparoscopic surgery for the treatment of heterotopic pregnancy
      and the secondary outcomes were obstetric outcomes. RESULTS: Seventeen women
      underwent laparoscopic surgery for heterotopic pregnancy: 14 with tubal
      heterotopic pregnancies and three with cornual heterotopic pregnancies. There
      were no intraoperative or postoperative complications. Of these women, 13
      delivered 14 healthy babies, whereas two failed to maintain their pregnancies;
      one had a missed abortion 2 weeks after the surgery and the other had a
      miscarriage due to preterm premature rupture of the membrane at 16 gestational
      weeks. The remaining two women have ongoing pregnancies. CONCLUSION: Laparoscopic
      surgery performed by experienced surgeons is a feasible and beneficial surgical
      modality for treating heterotopic pregnancy.

PMID- 23875925
TI  - Characterisation and analysis of thioredoxin peroxidase as a potential antigen
      for the serodiagnosis of sarcoptic mange in rabbits by dot-ELISA.
AB  - BACKGROUND: Scabies caused by Sarcoptes scabiei is a widespread but a neglected
      tropical zoonosis. In this study, we characterised a S. scabiei thioredoxin
      peroxidase (SsTPx) and evaluated a recombinant SsTPx as a diagnostic antigen in
      rabbits. METHODS: The open reading frame of the gene encoding SsTPx-2 was
      amplified and the recombinant protein was expressed in Escherichia coli cells and
      purified. SsTPx was localized in mite tissue by immunolocalisation using the
      purified recombinant protein. Serodiagnosis assays were carried out in 203 New
      Zealand White rabbit serum samples by dot-ELISA. RESULT: The open reading frame
      (489 bp) of the gene encodes an 18.11 kDa protein, which showed highly homology
      to that of Psoroptes cuniculi (98.77% identity) and belongs to the 2-Cys family
      of peroxiredoxins. SsTPx was mainly distributed in muscle tissues of mites,
      integument of the epidermis and the anterior end of S. scabiei. Although SsTPx
      cross-reactivity with psoroptic mites was observed, the SsTPx dot-ELISA showed
      excellent diagnostic ability, with 95.3% sensitivity and 93.8% specificity in
      mange-infected and uninfected groups. CONCLUSIONS: This study showed that the
      purified SsTPx is a highly sensitive antigen for the diagnosis of mange infection
      by dot-ELISA. This technique is a rapid and convenient method that can be used
      worldwide for the clinical diagnosis of sarcoptic mange in rabbits, and is
      especially useful in developing regions.

PMID- 23875927
TI  - A combinatorial approach to the restriction of a mouse genome.
AB  - BACKGROUND: A fragmentation of genomic DNA by restriction digestion is a popular
      step in many applications. Usually attention is paid to the expected average size
      of the DNA fragments. Another important parameter, randomness of restriction, is
      regularly implied but rarely verified. This parameter is crucial to the
      expectation, that either all fragments made by restriction will be suitable for
      the method of choice, or only a fraction of those will be effectively used by the
      method. If only a fraction of the fragments are used, we often should know
      whether the used fragments are representative of the whole genome. With a modern
      knowledge of mouse, human and many other genomes, frequencies and distributions
      of restriction sites and sizes of corresponding DNA fragments can be analyzed in
      silico. In this manuscript, the mouse genome was systematically scanned for
      frequencies of complementary 4-base long palindromes. FINDINGS AND CONCLUSIONS:
      The study revealed substantial heterogeneity in distribution of those sites
      genome-wide. Only few palindromes showed close to random pattern of distribution.
      Overall, the distribution of frequencies for most palindromes is much wider than
      expected by random occurrence. In practical terms, accessibility of genome upon
      restriction can be improved by a selective combination of restrictases using a
      few combinatorial rules. It is recommended to mix at least 3 restrictases, their
      recognition sequences (palindrome) should be the least similar to each other.
      Principles of the optimization and optimal combinations of restrictases are
      provided.

PMID- 23875928
TI  - Evaluating chemical extraction techniques for the determination of uranium
      oxidation state in reduced aquifer sediments.
AB  - Extraction techniques utilizing high pH and (bi)carbonate concentrations were
      evaluated for their efficacy in determining the oxidation state of uranium (U) in
      reduced sediments collected from Rifle, CO. Differences in dissolved
      concentrations between oxic and anoxic extractions have been proposed as a means
      to quantify the U(VI) and U(IV) content of sediments. An additional step was
      added to anoxic extractions using a strong anion exchange resin to separate
      dissolved U(IV) and U(VI). X-ray spectroscopy showed that U(IV) in the sediments
      was present as polymerized precipitates similar to uraninite and/or less ordered
      U(IV), referred to as non-uraninite U(IV) species associated with biomass
      (NUSAB). Extractions of sediment containing both uraninite and NUSAB displayed
      higher dissolved uranium concentrations under oxic than anoxic conditions while
      extractions of sediment dominated by NUSAB resulted in identical dissolved U
      concentrations. Dissolved U(IV) was rapidly oxidized under anoxic conditions in
      all experiments. Uraninite reacted minimally under anoxic conditions but
      thermodynamic calculations show that its propensity to oxidize is sensitive to
      solution chemistry and sediment mineralogy. A universal method for quantification
      of U(IV) and U(VI) in sediments has not yet been developed but the chemical
      extractions, when combined with solid-phase characterization, have a narrow range
      of applicability for sediments without U(VI). 

PMID- 23875930
TI  - Electrical characterization of conductive textile materials and its evaluation as
      electrodes for venous occlusion plethysmography.
AB  - The ambulatory monitoring of biosignals involves the use of sensors, electrodes,
      actuators, processing tools and wireless communication modules. When a garment
      includes these elements with the purpose of recording vital signs and responding
      to specific situations it is call a 'Smart Wearable System'. Over the last years
      several authors have suggested that conductive textile material (e-textiles)
      could perform as electrode for these systems. This work aims at implementing an
      electrical characterization of e-textiles and an evaluation of their ability to
      act as textile electrodes for lower extremity venous occlusion plethysmography
      (LEVOP). The e-textile electrical characterization is carried out using two
      experimental set-ups (in vitro evaluation). Besides, LEVOP records are obtained
      from healthy volunteers (in vivo evaluation). Standard Ag/AgCl electrodes are
      used for comparison in all tests. Results shown that the proposed e-textiles are
      suitable for LEVOP recording and a good agreement between evaluations (in vivo
      and in vitro) is found.

PMID- 23875931
TI  - Separation of heart sounds and heart murmurs by Hilbert transform envelogram.
AB  - Heart sounds and murmurs provide crucial diagnosis information for several heart
      diseases such as natural or prosthetic valve dysfunction and heart failure. Many
      pathological conditions of the cardiovascular system cause murmurs and
      aberrations in heart sounds. Phonocardiography provides the clinician with a
      complementary tool to record the heart sounds heard during auscultation. The
      advancement of intra-cardiac phonocardiography, combined with modern digital
      processing techniques, has strongly renewed researchers' interest in studying
      heart sounds and murmurs. This paper presents an algorithm for the detection of
      heart sounds (the first and second sounds, S1 and S2) and heart murmurs. The
      segmentation algorithm is based on the detection of the envelope of the
      phonocardiogram signal by the Hilbert transform technique, which is used to
      extract a smooth envelogram which enable one to apply the tests necessary for
      temporal localization of heart sounds and heart murmurs.

PMID- 23875929
TI  - Hidden consequences of olfactory dysfunction: a patient report series.
AB  - BACKGROUND: The negative consequences of olfactory dysfunction for the quality of
      life are not widely appreciated and the condition is therefore often ignored or
      trivialized. METHODS: 1,000 patients with olfactory dysfunction participated in
      an online study by submitting accounts of their subjective experiences of how
      they have been affected by their condition. In addition, they were given the
      chance to answer 43 specific questions about the consequences of their olfactory
      dysfunction. RESULTS: Although there are less practical problems associated with
      impaired or distorted odor perception than with impairments in visual or auditory
      perception, many affected individuals report experiencing olfactory dysfunction
      as a debilitating condition. Smell loss-induced social isolation and smell loss
      induced anhedonia can severely affect quality of life. CONCLUSIONS: Olfactory
      dysfunction is a serious condition for those affected by it and it deserves more
      attention from doctors who treat affected patients as well as from scientist who
      research treatment options.

PMID- 23875934
TI  - Infrared spectroscopy of solvation in small Zn+ (H2O)n complexes.
AB  - Singly charged zinc-water cations are produced in a pulsed supersonic expansion
      source using laser vaporization. Zn(+)(H2O)n (n = 1-4) complexes are mass
      selected and studied with infrared laser photodissociation spectroscopy,
      employing the method of argon tagging. Density functional theory (DFT)
      computations are used to obtain the structures and vibrational frequencies of
      these complexes and their isomers. Spectra in the O-H stretching region show
      sharp bands corresponding to the symmetric and asymmetric stretches, whose
      frequencies are lower than those in the isolated water molecule. Zn(+)(H2O)nAr
      complexes with n = 1-3 have O-H stretches only in the higher frequency region,
      indicating direct coordination to the metal. The Zn(+)(H2O)2-4Ar complexes have
      multiple bands here, indicating the presence of multiple low energy isomers
      differing in the attachment position of argon. The Zn(+)(H2O)4Ar cluster uniquely
      exhibits a broad band in the hydrogen bonded stretch region, indicating the
      presence of a second sphere water molecule. The coordination of the Zn(+)(H2O)n
      complexes is therefore completed with three water molecules. 

PMID- 23875935
TI  - Systematic literature review of incidence rates of low-speed vehicle run-over
      incidents in children.
AB  - AIM: To systematically review the literature investigating the incidence of fatal
      and or nonfatal low-speed vehicle run-over (LSVRO) incidents in children aged 0
      15 years. METHODS: The following databases were searched using specific search
      terms, from their date of conception up to June 2011: Cochrane Library, Medline,
      CINAHL, Embase, AMI, Sociological Abstracts, ERIC, PsycArticles, PsycInfo, Urban
      Studies and Planning; Australian Criminology Database; Dissertations and Thesis;
      Academic Research Library; Social Services Abstracts; Family and Society; Scopus;
      and Web of Science. A total of 128 articles were identified in the databases (33
      found by hand searching). The title and abstract of these were read, and 102 were
      removed because they were not primary research articles relating to LSVRO-type
      injuries. Twenty-six articles were assessed against the inclusion (reporting
      population level incidence rates) and exclusion criteria, 19 of which were
      excluded, leaving a total of five articles for inclusion in the review. FINDINGS:
      Five studies were identified that met the inclusion criteria. The incidence rate
      in nonfatal LSVRO events varied in the range of 7.09 to 14.79 per 100,000 and
      from 0.63 to 3.2 per 100,000 in fatal events. DISCUSSION: Using International
      Classification of Diseases codes for classifying fatal or nonfatal LSVRO
      incidents is problematic as there is no specific code for LSVRO. The current body
      of research is void of a comprehensive secular population data analysis. Only
      with an improved spectrum of incidence rates will appropriate evaluation of this
      problem be possible, and this will inform nursing prevention interventions. The
      effect of LSVRO incidents is clearly understudied. More research is required to
      address incidence rates in relation to culture, environment, risk factors, car
      design, and injury characteristics. CONCLUSIONS: The lack of nursing research or
      policy around this area of injury, most often to children, indicates a field of
      inquiry and policy development that needs attention.

PMID- 23875936
TI  - Chloroplast-targeted Hsp90 plays essential roles in plastid development and
      embryogenesis in Arabidopsis possibly linking with VIPP1.
AB  - The Arabidopsis genome contains seven members of Hsp90. Mutations in plastid
      AtHsp90.5 were reported to cause defects in chloroplast development and
      embryogenesis. However, the exact function of plastid AtHsp90.5 has not yet been
      defined. In this study, albino seedlings were found among AtHsp90.5 transformed
      Arabidopsis, which were revealed to be AtHsp90.5 co-suppressed plants. The
      accumulation of photosynthetic super-complexes in the albinos was decreased, and
      expression of genes involved in photosynthesis was significantly down-regulated.
      AtHsp90.5 T-DNA insertion mutants were embryo-lethal with embryo arrested at the
      heart stage. Further investigation showed AtHsp90.5 expression was up-regulated
      in the siliques at 4 days post anthesis (DPA). Confocal microscopy proved
      AtHsp90.5 was located in the chloroplasts. Plastid development in the AtHsp90.5
      mutants and co-suppressed plants was seriously impaired, and few thylakoid
      membranes were observed, indicating the involvement of AtHsp90.5 in chloroplast
      biogenesis. AtHsp90.5 was found to interact with vesicle-inducing protein in
      plastids 1 (VIPP1) by bimolecular fluorescence complementation system. The ratio
      between VIPP1 oligomers and monomers in AtHsp90.5 co-suppressed plants
      drastically shifted toward the oligomeric state. Our study confirmed that
      AtHsp90.5 is vital for chloroplast biogenesis and embryogenesis. Further evidence
      also suggested that AtHsp90.5 may help in the disassembly of VIPP1 for thylakoid
      membrane formation and/or maintenance.

PMID- 23875937
TI  - The interplay of received social support and self-regulatory factors in smoking
      cessation.
AB  - OBJECTIVE: In smoking cessation, individual self-regulation and social support
      have both proven to be useful. However, the roles of self-regulatory processes
      and social support are mostly examined separately. The present study aims at
      examining the unique and joint interactive effects of self-regulation as
      specified in the health action process approach (HAPA) and social support on
      smoking cessation. The study tested whether social support can compensate for low
      levels of self-regulation or whether synergistic effects emerge. DESIGN &
      MEASURES: Around a self-set quit date, 99 smokers completed baseline
      questionnaires on HAPA-variables, smoking-specific received social support and
      smoking cessation (continuous abstinence and point prevalence), with a follow-up
      Cpproximately 29 days after the quitdate. RESULTS: Social support moderated the
      association between volitional self-efficacy and smoking, as well as coping
      planning and smoking but not between action planning and smoking. No compensatory
      effect of social support for lower levels of individual regulation emerged but
      the combination of high levels of the individual variables and social support was
      related to successful smoking cessation, indicating a synergistic effect.
      CONCLUSIONS: The results confirm the importance of examining both self-regulation
      and social factors in smoking cessation. This should be considered when
      developing future interventions for smoking cessation.

PMID- 23875938
TI  - Advances in research of the artificial cultivation of Ophiocordyceps sinensis in
      China.
AB  - Ophiocordyceps sinensis (syn. Cordyceps sinensis), a traditional Chinese medicine
      called DongChongXiaCao (DCXC) in Chinese, is well known and has been used in Asia
      countries since the fifteenth century, and it contains some valuable medicinal
      component defined by modern pharmacological science. DCXC only appears at high
      altitudes on the Qinghai-Tibetan Plateau. Consequently, it is difficult to find
      and harvest. Because of its rarity and medicinal value, DCXC has always been one
      of the most expensive medicines known. As the price of DCXC has risen in recent
      years, thousands of migrants have entered into the various grasslands to search
      for them in season, which makes ecological environments of the grassland more
      fragile. In order to relieve the environmental pressures and protect this
      valuable resource, the artificial cultivation of DCXC involving two aspects of
      the genus Hepialus and the fungi of the host larvae should be employed and
      applied at the first available time point. In this article, the reproduction of
      moth larvae of the genus Hepialus is first described, which includes their
      ecological characteristics and the methods of artificial feeding. Second, the
      generation and isolation method of the fungi from DCXC are subsequently
      summarized, and then the mechanism of fungal spores to attack the moth larvae are
      restated. Finally, the basic model of artificial cultivation of DCXC is
      introduced; meanwhile, the potential application of modern biotechnology to the
      artificial cultivation is analyzed in prospect. This review article will not only
      expand people's knowledge regarding the artificial cultivation of DCXC, but also
      hopefully provide an informative reference for the development of this valuable
      resource and the environmental protection of alpine meadows.

PMID- 23875939
TI  - High-resolution DNA melt-curve analysis for cost-effective mass screening of
      pairwise species interactions.
AB  - Ecological studies of pairwise interactions are constrained by the methods
      available for rapid species identification of the interacting organisms. The
      resolution of data required to characterize species interaction networks at
      multiple spatio-temporal scales can be intensive, and therefore laborious and
      costly to collect. We explore the utility of high-resolution DNA melt-curve
      analysis (HRM) as a rapid species identification method. An approach was
      developed to identify organisms at the pairwise interaction level, with
      particular application to cryptic species interactions that are traditionally
      difficult to study. Here, we selected a challenging application; to identify the
      presence/absence of pathogenic fungi (Sporothrix inflata, Ophiostoma nigrocarpum
      and Ophiostoma galeiforme) transported by bark beetle vectors (Hylastes ater and
      Hylurgus ligniperda). The technique was able to distinguish between different
      species of DNA within a single, pooled sample. In test applications, HRM was
      effective in the mass screening and identification of pathogenic fungal species
      carried by many individual bark beetle vectors (n = 455 beetles screened) across
      large geographic scales. For two of the fungal species, there was no difference
      in the frequency of association with either of their vectors, but for the third
      fungal species there was a shift in vector-pathogen associations across
      locations. This technique allows rapid, mass screening and characterization of
      species interactions at a fraction of the time and cost of traditional methods.
      It is anticipated that this method can be readily applied to explore other
      cryptic species interactions, or other studies requiring rapid generation of
      large data sets and/or high-throughput efficiency. 

PMID- 23875940
TI  - Ultrastructural examination of renal tubular epithelial cells and hepatocytes in
      the course of chronic cyclosporin A treatment--a possible link to oxidative
      stress.
AB  - Cyclosporin A is an immunosuppressant drug used to prevent graft rejection in
      organ transplantation. Side effects include toxicity to the kidney and liver.
      Recently, many experimental and clinical data have demonstrated that CsA-induced
      toxicity is associated with increased production of reactive oxygen species (ROS)
      and lipid peroxidation in the kidney and liver. The aim of the study was
      ultrastructural examination of renal and liver epithelial cells in the course of
      chronic experimental CsA treatment. Rats were treated with CsA in a dose of 25
      mg/kg/day. Animals developed failure of the kidney and the liver functions
      manifested by an increase in serum levels of creatinine, urea, uric acid,
      bilirubin, AST, and ALT and a decrease in total proteins. Ultrastructural
      examination of tubular epithelial cells and hepatocytes revealed dilatation of
      endoplasmic reticulum and injury to mitochondria, formation of autolysosomes, and
      presence of single apoptotic cells. On the basis of a review of the literature
      the authors suggest that mitochondrial and cell membrane system changes are, at
      least in part, a result of oxidative damage to the liver and renal tubular
      epithelial cells.

PMID- 23875941
TI  - Au-nanoparticle-loaded graphitic carbon nitride nanosheets: green photocatalytic
      synthesis and application toward the degradation of organic pollutants.
AB  - Au nanoparticles (AuNPs) were loaded on graphitic carbon nitride (g-C3N4)
      nanosheets prepared by ultrasonication-assisted liquid exfoliation of bulk g-C3N4
      via green photoreduction of Au(III) under visible light irradiation using g-C3N4
      as an effective photocatalyst. The nanohybrids show superior photocatalytic
      activities for the decomposition of methyl orange under visible-light irradiation
      to bulk g-C3N4, g-C3N4 nanosheets, and AuNP/bulk g-C3N4 hybrids. 

PMID- 23875942
TI  - Surface roughness of acrylic and silicone-based soft liners: in vivo study in a
      rat model.
AB  - PURPOSE: The aim of this in vivo animal study was to investigate changes in the
      surface roughness of soft liners over time. MATERIALS AND METHODS: Forty adult
      Wistar rats (Rattus norvergicus albinus) were fitted with acrylic custom-made
      palatal plates relined by dynamic impressions and tested with the following soft
      liners: Dentuflex (DF), Trusoft (TS), Dentusoft (DS), and Ufi Gel P (UG). Half of
      the animals for each tested material had the plates fitted during the material
      reline procedure. Their surface roughness was read immediately (IRa group, n =
      5). The other half used the palatal plates for 14 days before roughness readings
      were performed (FRa group, n = 5). The surface roughness (Ra) of the inner
      surface from the relined dentures was recorded using a Surftest SJ-401 with eight
      readings per specimen, and mean values were obtained. Data (MUm) were analyzed by
      two-way ANOVA and Tukey's test (alpha = 0.05). RESULTS: IRa means (2.92 +/- 0.87
      MUm) and FRa means (3.35 +/- 0.65 MUm) were significantly different (p = 0.016).
      UG showed a lower (p = 0.01) Ra mean (2.1 +/- 0.52 MUm) than DF (3.94 +/- 0.81
      MUm), TS (4.12 +/- 0.64 MUm), and DS (3.27 +/- 0.64 MUm). CONCLUSIONS: Ufi Gel P
      showed the smoothest surface among the materials evaluated. The period of use
      resulted in changes in the surface roughness of the materials tested.

PMID- 23875943
TI  - ECM-incorporated hydrogels cross-linked via native chemical ligation to engineer
      stem cell microenvironments.
AB  - Limiting the precise study of the biochemical impact of whole molecule
      extracellular matrix (ECM) proteins on stem cell differentiation is the lack of
      3D in vitro models that can accommodate many different types of ECM. Here we
      sought to generate such a system while maintaining consistent mechanical
      properties and supporting stem cell survival. To this end, we used native
      chemical ligation to cross-link poly(ethylene glycol) macromonomers under mild
      conditions while entrapping ECM proteins (termed ECM composites) and stem cells.
      Sufficiently low concentrations of ECM were used to maintain constant storage
      moduli and pore size. Viability of stem cells in composites was maintained over
      multiple weeks. ECM of composites encompassed stem cells and directed the
      formation of distinct structures dependent on ECM type. Thus, we introduce a
      powerful approach to study the biochemical impact of multiple ECM proteins
      (either alone or in combination) on stem cell behavior. 

PMID- 23875944
TI  - Topical azithromycin as a novel treatment for ocular rosacea.
AB  - PURPOSE: Acne rosacea is a common dermatological conditions associated with
      blepharitis. Current treatments include artificial tears, lid hygiene, and
      systemic doxycycline. In this study the authors evaluate the effectiveness of
      topical azithromycin in ocular rosacea. METHODS: The authors enrolled 37 ocular
      rosacea patients: 12 were treated with systemic doxycycline, 16 with azithromycin
      eyedrops, and 9 did not receive medical treatments. Ocular signs and symptoms and
      side effects were evaluated at baseline and at 1-month follow-up. RESULTS: A
      significant improvement in TF-BUT, meibomian gland plugging, and Oxford score
      associated with symptom reduction was reported by all patients after 1 month. All
      treatments were well tolerated, with mild gastro-intestinal symptoms in 33% of
      the doxycycline group and mild burning after instillation in the azithromycin
      group. CONCLUSIONS: Topical azithromycin may represent an additional treatment
      for ocular rosacea, with a shorter duration of treatment and absence of
      gastrointestinal side effects as compared to systemic doxycycline.

PMID- 23875945
TI  - Post abortion care quality status in health facilities of Guraghe zone, Ethiopia.
AB  - BACKGROUND: Unsafe abortion in the developing world accounts for 13% of all
      maternal deaths. Ethiopia is one of the developing countries with the highest
      maternal mortality ratio (673 per 100,000 live births) in the world. Unsafe
      abortion was estimated to account for 32% of all maternal deaths in Ethiopia.
      OBJECTIVE: To assess post abortion care quality status in health facilities of
      Guraghe zone. METHODS: A facility based cross-sectional study design with both
      quantitative and qualitative methods was conducted. Patient interview, direct
      service observation, provider self administered questionnaire and inventory of
      equipment and supplies were used for the assessment. Six health centers, two
      hospitals and 422 post-abortion patients were included in the study. RESULTS:
      Patient-provider interaction was generally satisfactory from the patient's
      perspective. The majority of the respondents (93.5%) said that they were treated
      with politeness and respect. More than half 226(56.5%) of the clients have
      received post abortion family planning. Overall, 83.5% of the patients were
      satisfied with the services. Those who said waiting time was long were less
      satisfied and unemployed women were more satisfied than others. CONCLUSION: The
      study has revealed several improvements as well as problems in the provision of
      post-abortion care service in the studied health facilities.

PMID- 23875946
TI  - Agency in young clients' narratives of counseling: "it's whatever you want to
      make of it".
AB  - Although there is a growing body of research that looks at how adult clients are
      active agents in their own counseling, there is little similar research that
      looks at the experiences of young people in counseling. This research explores
      how client agency is constructed in retrospective accounts of a school counseling
      experience provided by 22 young people (aged 16-18). The narrative analysis shows
      how participants constructed their agency as clients in a number of different
      ways: in asserting their choice over whether to see a counselor; in their
      evaluations of counselors; in the selection or rejection of aspects of counseling
      and by portraying themselves as primarily responsible for the benefits obtained
      from counseling. In these ways, young clients seemed able to shape their
      construction of counseling to better match their own priorities. But participants
      also seemed aware of potential threats to their ability to exercise their agency
      and described how they struggled to express their needs overtly to their
      counselors. This raises the possibility that young people's assertions of agency
      may be best understood in the context of their relative powerlessness in
      counseling situations. Although there is potential to harness young clients'
      agency in the service of better counseling outcomes, their strong commitment to a
      view of themselves as agents may result in them experiencing greater
      accountability without a corresponding access to power in counseling.

PMID- 23875948
TI  - Biomarkers for personalised treatment in psychiatric diseases.
AB  - Biomarker research of psychiatric disorders is delayed by symptom pattern-related
      diagnostic categories that are only distantly associated with biological
      mechanisms. In neuropsychiatric disorders that have high heritability
      (schizophrenia, autism, Alzheimer's disease), genomic research led to significant
      genome-wide association study (GWAS) results by increasing the number of subjects
      in case-control studies, and thus provided new hypotheses regarding the aetiology
      of these disorders and possible targets for research of new treatment approaches.
      In contrast, in moderately heritable psychiatric disorders (anxiety disorders,
      unipolar major depression), the development of symptoms, in addition to risk
      genes, is more dependent on the presence of specific environmental risk factors.
      Thus, controlling for heterogeneity, and not simply increasing the number of
      subjects, is crucial for further significant psychiatric GWAS findings that
      warrant the collection of more detailed individual phenotypic data and
      information about relevant previous environmental exposures. Gene-gene
      interactions (epistasis) and intermediate phenotypes or psychiatric and somatic
      co-morbidities, by identifying similar cases within a diagnostic category, could
      further increase the generally weak effects of individual genes that limit their
      usefulness as biomarkers. In conclusion, we argue that methods that are suitable
      to identify biologically more homogeneous subgroups within a given psychiatric
      disorder are necessary to advance biomarker research. 

PMID- 23875947
TI  - A grounded theory exploration of undergraduate experiences of vicarious
      unemployment.
AB  - The experiences of vicarious unemployment (VU) among 17 undergraduate student
      participants who had a primary caregiver who was involuntarily unemployed were
      explored using grounded theory (Charmaz, 2006; Glaser & Strauss, 1967). Data from
      semistructured interviews with 15 women and 2 men revealed the nuanced nature of
      experiences with unemployment among those who experience it vicariously.
      Struggles related to increased family stress and experiences with stigma were
      common across participants. As participants reflected upon these challenges, they
      both lamented the costs associated with the struggles and expressed appreciation
      for the lessons that they have learned. They emerged from their VU experiences
      with increased financial and job market awareness, which informed their hope for
      a life that is free from the struggles endured in their families. Participants
      expressed confidence in their ability to cultivate financial security for their
      own families, stable employment, and opportunities to pursue work that will allow
      them to give back to others. Implications for counseling and directions for
      future research are discussed.

PMID- 23875949
TI  - Laparoscopic ovarian-sparing surgery for a young woman with an exophytic ovarian
      fibroma.
AB  - Ovarian fibroma can occur in young women of reproductive age. Despite its benign
      feature, most surgical removals are done in open surgery with oophorectomy.
      However, an ovarian-sparing tumor resection can be an option, especially for an
      exophytic type of fibroma, which accounts for more than half of ovarian fibromas.
      Here we report a case of exophytic ovarian fibroma in a young woman treated by
      laparoscopic ovarian-sparing surgery. A 27-year-old woman presented with a pelvic
      mass. Magnetic resonance imaging revealed an 11 cm * 8 cm solid mass connected to
      the normal-appearing left ovary by a pedicle-like structure. A clinical diagnosis
      of an exophytic ovarian fibroma was made, and laparoscopic ovarian-sparing
      surgery with an intraoperative pathological examination was planned. The tumor
      was resected by cutting the pedicle, morcellated in a pouch and removed. All
      procedures were performed laparoscopically and the affected ovary was completely
      preserved. Having confirmation of its benign characteristics by the
      intraoperative examination, no further excision was performed. The patient
      conceived 3 months after the surgery and no recurrence was reported. We propose
      that gynecologists should consider laparoscopic ovarian-sparing surgery for
      exophytic ovarian fibroma in women of reproductive age.

PMID- 23875950
TI  - Surveillance study of species distribution, antifungal susceptibility and
      mortality of nosocomial candidemia in a tertiary care hospital in China.
AB  - BACKGROUND: Bloodstream infections due to Candida species cause significant
      morbidity and mortality, and the epidemiology of Candida infection is changing.
      Surveillance for candidemia is necessary to detect trends in species distribution
      and antifungal resistance. METHODS: The medical and electronic records of all
      patients who had candidemia at the authors' hospital from 2009 to 2011 were
      reviewed for demographic data and clinical information, including the infecting
      Candida species, resistance to antifungals and survival, and the presence of risk
      factors associated with candidemia. RESULTS: A total of 133 distinct episodes of
      candidemia were identified over the study period. The annual incidence of
      candidemia ranged between 0.71 and 0.85 cases/1000 hospital discharges. The most
      frequent Candida species were C. tropicalis (28.6%), followed by C. albicans
      (23.3%) and C. parapsilosis (19.5%). The rates of susceptibility to antifungal
      agents were as followed: voriconazole (97.8%), itraconazole (69.5%), fluconazole
      (46.1%), ketoconazole (38.9%). Out of 131 evaluable patients, 34 (26.0%) died
      within 30 days from the onset of candidemia. C. tropicalis candidemia was
      associated with the highest mortality rate (44.7%). Regarding the crude mortality
      in the different units, patients in Hemato-Oncology ward had the highest
      mortality rate (66.7%), followed by patients in cardiovascular wards and ICU
      (57.1% and 25.6%, respectively). Predictors of 30-day mortality were identified
      by uni- and multivariate analyses. Complicated abdominal surgery, presence of
      central venous catheter (CVC), neutropenia, candidemia due to C. tropicalis and
      poor treatment with fluconazole were significantly associated with the 30-day
      mortality. Presence of CVC (odds ratio[OR] = 4.177; 95% confidence interval [CI]
      = 1.698 to 10.278; P = 0.002) was the only independent predictor for mortality in
      the multivariate analysis. CONCLUSION: This report provides baseline data for
      future epidemiological and susceptibility studies and for the mortality rates
      associated with candidemia in our hospital. The knowledge of the local
      epidemiological trends in Candida species isolated in blood cultures is important
      to guide therapeutic choices.

PMID- 23875951
TI  - Smart meters and routers radiofrequency disturbances study with pacemakers and
      implantable cardiac defibrillators.
AB  - BACKGROUND: There is no scientific literature that examines radiofrequency (RF)
      interference from Smart Meters with cardiac implantable electronic devices
      (CIEDs). The objective of this in vitro study was to assess any potential
      interference with Medtronic CIEDs (Medtronic Inc., Minneapolis, MN, USA).
      METHODS: In the Quebec testing, five models of Medtronic CIEDs were placed in an
      acrylic cylinder filled with a saline solution and faced a Landis+Gyr Smart Meter
      or Router (Landis+Gyr AG, Zug, Switzerland). The distance between CIEDs and the
      meter casing or router antenna was 10 cm. The Meter's normal operating conditions
      were modified to artificially set the number of impulsions at an abnormally high
      level (one, two, and three impulses per second). Each scenario was repeated one
      to five times, for 1 minute each. In the U.S. testing, 6 cm and 15 cm (~2.25' and
      ~6') separated the six models of Medtronic CIEDs from the Schlumberger Smart
      Meter (Itron Inc., Liberty Lake, WA, USA), which generally sent out a 96-bit
      Standard Consumption Message over 3 seconds. The transmission varied in
      frequencies along with the interval between cycles. RESULTS: A total of 6,966 RF
      transmissions were completed during the 34 tests conducted in Quebec. In the
      United States, the CIED was exposed to the meter for 10 minutes to provide a
      minimum of 200 completed RF transmissions. No interference was observed in worst
      case scenarios (testing of meters and CIEDs at their performance limits).
      CONCLUSIONS: Landis+Gyr Smart Meters/Routers and Schlumberger Smart Meters do not
      interfere with the functioning of the Medtronic CIEDs tested, when placed,
      respectively, 10 cm and 6 cm and 15 cm apart.

PMID- 23875952
TI  - Quantification and comparison of psychiatric distress in African patients with
      albinism and vitiligo: a 5-year prospective study.
AB  - BACKGROUND: Vitiligo and albinism are two disorders of pigmentation that make the
      affected African highly visible and strikingly different from their peers. Both
      pose considerable management challenges, attract significant stigma and profound
      impairment of quality of life. OBJECTIVE AND METHODS: To determine and compare
      psychiatric distress in vitiligo and albinism using the Hospital Anxiety and
      Depression Scale (HADS). Participants were 87 albinos and 102 vitiligo adult
      patients seen at an urban tertiary hospital in Nigeria between 2004 and 2009.
      RESULTS: Prevalence of psycho morbidity was 59% (60/102) in vitiligo compared
      with 26% (23/87) in the albinos. The mean anxiety score was estimated to be 2.55
      points lower for albino patients (95% CI: 1.47 to 3.64), and the mean depression
      score 2.76 points lower (95% CI: 1.84 to 3.68), after adjustment for age, sex and
      marital status. However, significant differences were not observed when comparing
      the vitiligo patients with the subset of albino patients with skin cancer. Older
      patients had significantly higher anxiety and depression scores. Females had
      significantly higher anxiety scores (but not depression scores) compared to
      males. Genital involvement in vitiligo was significantly associated with anxiety
      but not depression. CONCLUSIONS: We found that the African with vitiligo suffers
      significantly higher psychiatric distress than the African albino on average.
      Clinical evaluation of these patients would be incomplete without assessment of
      their psycho morbidity. There is need for increased focus on cancer prevention
      strategies in the African albino.

PMID- 23875953
TI  - Spray absorption and electrochemical reduction of nitrogen oxides from flue gas.
AB  - This work developed an electrochemical reduction system which can effectively
      scrub NO* from flue gas by using aqueous solution of Fe(II)(EDTA)
      (ethylenediaminetetraacetate) as absorbent and electrolyte. This new system
      features (a) complete decomposition of NOX to harmless N2; and (b) fast
      regeneration of Fe(II)(EDTA) through electrochemical reaction. The Fe(II)(EDTA)
      solution was recycled and reused continuously during entire process, and no
      harmful waste was generated. The reaction mechanism was thoroughly investigated
      by using voltammetric, chromatographic and spectroscopic approaches. The
      operating conditions of the system were optimized based on NOX removal
      efficiency. Approximately 98% NO removal was obtained at the optimal condition.
      The interference of SO2 in flue gas and the system operating stability was also
      evaluated. 

PMID- 23875954
TI  - The radiosensitizing effect of Paeonol on lung adenocarcinoma by augmentation of
      radiation-induced apoptosis and inhibition of the PI3K/Akt pathway.
AB  - PURPOSE: To investigate the radiosensitizing effect and mechanism of action by
      the natural product Paeonol on lung adenocarcinoma both in vitro and in vivo.
      MATERIALS AND METHODS: Two lung adenocarcinoma cell lines (human lung
      adenocarcinoma cell line A549 and mouse Lewis lung carcinoma (LLC) cell line)
      were chosen for this research. In order to select the experimental concentrations
      of Paeonol, cytotoxicity was determined using a MTT (3-[4,5-dimethylthiazol-2-yl]
      2,5- diphenyltetrazolium bromide) assay. A clonogenic assay was performed to
      measure the radiosensitizing effects. Apoptosis was determined by the Tunel
      (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) assay and
      flow cytometry. Protein expression was analyzed by Western blotting. To test the
      radiosensitizing effect in vivo, a transplanted tumor model was established.
      RESULTS: The MTT assay showed that Paeonol inhibited proliferation of cells.
      Paeonol concentration ranged from an IC5 (5% inhibiting concentration) to an IC20
      and was used at non-toxic concentrations for subsequent experiments. The
      clonogenic assay showed that Paeonol enhanced the radiosensitivity of cells. Data
      from the Tunel assay and flow cytometry verified that Paeonol enhanced radiation
      induced apoptosis. Paeonol inhibited the activation of the PI3K/AKT
      (Phosphatidylinositol 3-kinase/ Protein Kinase B) pathway and down-regulated the
      expression of COX-2 (Cyclooxygenase-2) and Survivin. Paeonol (1718 mg/kg)
      combined with 10 Gy irradiation inhibited the growth of a transplanted tumor
      model in vivo, resulting in the longest tumor growth time, tumor growth delay and
      the highest inhibition ratio when compared with the radiotherapy alone group.
      CONCLUSIONS: It is reported for the first time that Paeonol has a
      radiosensitizing effect on lung adenocarcinoma both in vitro and in vivo. This
      effect could be related to the augmentation of radiation-induced apoptosis and
      the inhibition of the PI3K/Akt signalling pathway and its downstream proteins:
      COX-2 and Survivin.

PMID- 23875955
TI  - Solvent-dependent stabilization of metastable monolayer polymorphs at the liquid
      solid interface.
AB  - Self-assembly of 1,3,5-tris(4'-biphenyl-4"-carbonitrile)benzene monolayers was
      studied at the liquid-solid interface by scanning tunneling microscopy.
      Application of different fatty acid homologues as solvents revealed a solvent
      induced polymorphism. Yet, tempering triggered irreversible phase transitions of
      the initially self-assembled monolayers, thereby indicating their metastability.
      Interestingly, in either case, the same thermodynamically more stable and more
      densely packed monolayer polymorph was obtained after thermal treatment,
      irrespective of the initial structure. Again, the same densely packed structure
      was obtained in complementary solvent-free experiments conducted under ultrahigh
      vacuum conditions. Thus, self-assembly of metastable polymorphs at room
      temperature is explained by adsorption of partially solvated species under
      kinetic control. The irreversible phase transitions are induced by thermal
      desolvation, that is, desorption of coadsorbed solvent molecules.

PMID- 23875956
TI  - Adenosquamous carcinoma of the parotid gland.
AB  - Adenosquamous carcinoma (ASC) is a rare malignant tumor in the head and neck
      region and usually it occurs as a mucosal carcinoma. The World Health
      Organization classification1 shows this tumor as a variation of squamous cell
      carcinoma (SCC), whereas the Armed Forces Institute of Pathology (AFIP)
      classification2 categorized it as a salivary gland tumor. In the AFIP guidelines,
      the occurrence of ASC is limited to the minor salivary glands not in the major
      salivary glands. This article is protected by copyright. All rights reserved.

PMID- 23875957
TI  - Improving palliative care outcomes for Aboriginal Australians: service providers'
      perspectives.
AB  - BACKGROUND: Aboriginal Australians have a lower rate of utilisation of palliative
      care services than the general population. This study aimed to explore care
      providers' experiences and concerns in providing palliative care for Aboriginal
      people, and to identify opportunities for overcoming gaps in understanding
      between them and their Aboriginal patients and families. METHODS: In-depth,
      qualitative interviews with urban, rural and remote palliative care providers
      were undertaken in inpatient and community settings in Western Australia.
      Interviews were audio-recorded, transcribed verbatim and coded independently by
      two researchers with QSR NVivo 10 software used to help manage data. Data
      analysis was informed by multiple theoretical standpoints, including the social
      ecological model, critical cultural theories and the 'cultural security'
      framework. Thematic analysis was carried out that identified patterns within
      data. RESULTS: Fifteen palliative care providers were interviewed. Overall they
      reported lack of understanding of Aboriginal culture and being uncertain of the
      needs and priorities of Aboriginal people during end-of-life care. According to
      several participants, very few Aboriginal people had an understanding of
      palliative care. Managing issues such as anger, denial, the need for non-medical
      support due to socioeconomic disadvantage, and dealing with crises and conflicts
      over funeral arrangements were reported as some of the tensions between
      Aboriginal patients and families and the service providers. CONCLUSION: Early
      referral to palliative care is important in demonstrating and maintaining a
      caring therapeutic relationship. Paramount to meeting the needs for Aboriginal
      patients was access to appropriate information and logistical, psychological and
      emotional support. These were often seen as essential but additional to standard
      palliative care services. The broader context of Aboriginal history and
      historical distrust of mainstream services was seen to impinge on Aboriginal
      people's willingness and ability to accept care and support from these services.
      This context needs to be understood and acknowledged at the system level. More
      cultural safety training was requested by care providers but it was not seen as
      replacing the need for an Aboriginal worker in the palliative care team.

PMID- 23875958
TI  - Oxidative decomposition of propylene carbonate in lithium ion batteries: a DFT
      study.
AB  - This paper reports an in-depth mechanistic study on the oxidative decomposition
      of propylene carbonate in the presence of lithium salts (LiClO4, LiBF4, LiPF6,
      and LiAsF6) with the aid of density functional theory calculations at the B3LYP/6
      311++G(d,p) level of theory. The solvent effect is accounted for by using the
      implicit solvation model with density method. Moreover, the rate constants for
      the decompositions of propylene carbonate have been investigated by using
      transition-state theory. The shortening of the original carbonyl C-O bond and a
      lengthening of the adjacent ethereal C-O bonds of propylene carbonate, which
      occurs as a result of oxidation, leads to the formation of acetone radical and
      CO2 as a primary oxidative decomposition product. The termination of the primary
      radical generates polycarbonate, acetone, diketone, 2-(ethan-1-ylium-1-yl)-4
      methyl-1,3-dioxolan-4-ylium, and CO2. The thermodynamic and kinetic data show
      that the major oxidative decomposition products of propylene carbonate are
      independent of the type of lithium salt. However, the decomposition rate
      constants of propylene carbonate are highly affected by the lithium salt type. On
      the basis of the rate constant calculations using transition-state theory, the
      order of gas volume generation is: [PC-ClO4](-) > [PC-BF4](-) > [PC-AsF6](-) >
      [PC-PF6](-). 

PMID- 23875959
TI  - Fear of recurrence.

PMID- 23875960
TI  - Neuropsychological outcomes in epilepsy surgery patients with unilateral
      hippocampal sclerosis and good preoperative memory function.
AB  - We examined postoperative changes in the memory function of 68 people with
      unilateral hippocampal sclerosis (HS) who underwent epilepsy surgery and had no
      previous clinical memory impairments. One in four with right HS (RHS) and one in
      five with left HS (LHS) in our sample of 323 people with unilateral HS performed
      within normal limits on memory tests that are sensitive to hippocampal pathology
      in group studies. People with intact memory function prior to surgery were
      significantly younger and had higher IQs than those with memory impairments. The
      majority of those with intact memory functions prior to surgery had significant
      postoperative declines on the memory measures at the 1-year follow-up and no
      longer functioned within the average range. People with RHS and left LHS were
      equally at risk of a postoperative decline. Postoperative deterioration was not
      related to seizure outcome. A higher IQ appears to protect against postoperative
      memory decline in this group. This finding does not support the notion that
      intact memory function in people with unilateral HS represents a migration of
      memory function to the contralateral structures, and thus protection from
      surgical insult. People with good preoperative memory function in the context of
      unilateral HS should therefore be counseled regarding the likelihood of a
      significant postoperative decline in memory function following a temporal lobe
      resection.

PMID- 23875961
TI  - Assessment and improvement of statistical tools for comparative proteomics
      analysis of sparse data sets with few experimental replicates.
AB  - Large-scale quantitative analyses of biological systems are often performed with
      few replicate experiments, leading to multiple nonidentical data sets due to
      missing values. For example, mass spectrometry driven proteomics experiments are
      frequently performed with few biological or technical replicates due to sample
      scarcity or due to duty-cycle or sensitivity constraints, or limited capacity of
      the available instrumentation, leading to incomplete results where detection of
      significant feature changes becomes a challenge. This problem is further
      exacerbated for the detection of significant changes on the peptide level, for
      example, in phospho-proteomics experiments. In order to assess the extent of this
      problem and the implications for large-scale proteome analysis, we investigated
      and optimized the performance of three statistical approaches by using simulated
      and experimental data sets with varying numbers of missing values. We applied
      three tools, including standard t test, moderated t test, also known as limma,
      and rank products for the detection of significantly changing features in
      simulated and experimental proteomics data sets with missing values. The rank
      product method was improved to work with data sets containing missing values.
      Extensive analysis of simulated and experimental data sets revealed that the
      performance of the statistical analysis tools depended on simple properties of
      the data sets. High-confidence results were obtained by using the limma and rank
      products methods for analyses of triplicate data sets that exhibited more than
      1000 features and more than 50% missing values. The maximum number of
      differentially represented features was identified by using limma and rank
      products methods in a complementary manner. We therefore recommend combined usage
      of these methods as a novel and optimal way to detect significantly changing
      features in these data sets. This approach is suitable for large quantitative
      data sets from stable isotope labeling and mass spectrometry experiments and
      should be applicable to large data sets of any type. An R script that implements
      the improved rank products algorithm and the combined analysis is available. 

PMID- 23875962
TI  - The effect of transforming care at the bedside initiative on healthcare teams'
      work environments.
AB  - BACKGROUND: Different initiatives have been implemented in healthcare
      organizations to improve efficiency, such as transforming care at the bedside
      (TCAB). However, there are important gaps in understanding the effect of TCAB on
      healthcare teams' work environments. AIM: The specific aim of the study is to
      describe findings regarding the TCAB initiative effects on healthcare teams' work
      environments. METHODS: A pretest and posttest study design was used for this
      study. The TCAB initiative was implemented in fall 2010 in a university health
      center in Montreal, Canada. The sample consisted of healthcare workers from four
      different care units. RESULTS: Statistically significant improvement was observed
      with the communicating specific information subscale from the measure of
      processes of care variable, and a significant difference was found between the
      support from colleagues variable, which was higher at baseline than postprogram.
      The differences for psychological demand, decisional latitude, and effort-reward
      were not significant. CONCLUSIONS: TCAB is an intervention that allows healthcare
      teams to implement change to improve patients' and families' outcomes. Ongoing
      energy should focus on how to improve communication among all members of the team
      and ensure their support.

PMID- 23875963
TI  - Influence of full-contour zirconia surface roughness on wear of glass-ceramics.
AB  - PURPOSE: The purpose of this study was to evaluate the influence of full-contour
      (Y-TZP) zirconia surface roughness (glazed vs. as-machined) on the wear behavior
      of glass-ceramics. MATERIALS AND METHODS: Thirty-two full contour Y-TZP
      (Diazir(r)) specimens (hereafter referred to as zirconia sliders) (phi = 2 mm,
      1.5 mm in height) were fabricated using CAD/CAM and sintered according to the
      manufacturer's instructions. Zirconia sliders were embedded in brass holders
      using acrylic resin and then randomly assigned (n = 16) according to the surface
      treatment received, that is, as-machined or glazed. Glass-ceramic antagonists,
      Empress/EMP and e.max/EX, were cut into tabs (13 * 13 * 2 mm(3) ), wet-finished,
      and similarly embedded in brass holders. Two-body pin-on-disk wear testing was
      performed at 1.2 Hz for 25,000 cycles under a 3 kg load. Noncontact profilometry
      was used to measure antagonist height (MUm) and volume loss (mm(3) ). Qualitative
      data of the zirconia testing surfaces and wear tracks were obtained using SEM.
      Statistics were performed using ANOVA with a significance level of 0.05. RESULTS:
      As-machined yielded significantly higher mean roughness values (Ra = 0.83 MUm, Rq
      = 1.09 MUm) than glazed zirconia (Ra = 0.53 MUm, Rq = 0.78 MUm). Regarding glass
      ceramic antagonist loss, as-machined zirconia caused significantly less mean
      height and volume loss (68.4 MUm, 7.6 mm(3) ) for EMP than the glazed group (84.9
      MUm, 9.9 mm(3) ), while no significant differences were found for EX. Moreover,
      EMP showed significantly lower mean height and volume loss than EX (p < 0.0001).
      SEM revealed differences on wear characteristics between the glass-ceramics
      tested. CONCLUSION: e.max wear was not affected by zirconia surface roughness;
      however, Empress wear was greater when opposing glazed zirconia. Overall, surface
      glazing on full-contour zirconia did not minimize glass-ceramic wear when
      compared with as-machined zirconia.

PMID- 23875964
TI  - Endometriosis and IVF: are agonists really better? Analysis of 1180 cycles with
      the propensity score matching.
AB  - OBJECTIVE: To compare the outcomes of patients with confirmed endometriosis
      undergoing in vitro fertilization (IVF)-embryo transfer (ET) treated with either
      gonadotropin-releasing hormone agonist (GnRHa) or gonadotropin-releasing hormone
      antagonist (GnRHant) using the propensity score (PS) matching. DESIGN:
      Observational, retrospective analysis from January 2000 to December 2010.
      SETTING: Private tertiary fertility clinic. PATIENT(S): Patients with
      endometriosis confirmed by ultrasound or surgery (American Fertility Society; AFS
      grades I-IV) that underwent an IVF-ET, stimulated with standard controlled
      ovarian hyperstimulation (COH) and GnRHa or GnRHant. INTERVENTION(S): A PS was
      assigned to all patients, which calculates the conditional probability of
      receiving a certain treatment; a higher PS (1) meant a higher probability of
      receiving treatment with GnRHa, and a lower PS (0) meant a higher probability of
      receiving GnRHant. The PS was calculated with a logistic regression model
      adjusted specifically for age, follicle stimulating hormone, antral follicle
      count and previous IVF cycles. All patients were divided into three groups
      according to their PS. MAIN OUTCOME MEASURE(S): pregnancy rate (PR) per cycle.
      RESULTS: 1180 patients were analyzed. Raw PR per cycle was 41.8% and 23.4%, and
      PR per ET was 44.3 and 27%, respectively. PR per cycle: 41.9 versus 30% in group
      A; in group B, 39.7% versus 36.4% and in group C, 15.4% versus 18.9%. The overall
      odds ratio for PR adjusted by PS was 1.10 [0.58-2.19]. CONCLUSIONS: After
      matching patients by PS, PR after COH with either GnRHa or GnRHant may be equally
      effective.

PMID- 23875965
TI  - The effects of different hormone treatment on endothelial function in healthy
      postmenopausal women.
AB  - We aimed to compare the effects of different types of hormone treatment (HT) on
      endothelial function by means of brachial artery ultrasonographic examination in
      postmenopausal women. Sixty-two healthy postmenopausal women were included in
      this study. Subjects were assigned to one of the five groups receiving 6 months
      of treatment [estrogen (conjugated estrogen), estrogen (conjugated estrogen) plus
      progesterone (medroxyprogesterone acetate; MPA), raloxifene, tibolone or
      control]. Endothelial function was assessed by measurement of flow-mediated
      dilatation (FMD) and nitrate-dependent dilatation in the brachial artery. At the
      end of 6 months, FMD values were found to be significantly increased in women
      with HT use than the control group (p = 0.001). In subgroups, FMD increased
      significantly in the estrogen [12 +/- 7 versus 25 +/- 8, p = 0.001] and
      raloxifene groups [7 +/- 5 versus 11 +/- 3, p < 0.01] compared to tibolone and
      estrogen plus progesterone groups. In conclusion, endothelial function is
      impaired in postmenopausal women. Both estrogen and raloxifene regimens may
      improve endothelial functions in healthy postmenopausal women. The direct
      protective effects of these HT on the healthy endothelium may be more remarkable
      than the favorable effects on lipid profile.

PMID- 23875966
TI  - Low rates of child testing for HIV persist in a high-risk area of East Africa.
AB  - Children in low- and middle-income countries (LMIC) are the least touched by
      recent successes in the diagnosis and treatment of HIV/AIDS globally. Early
      treatment is essential for a child's longer and higher quality of life; however,
      by 2011, only a small proportion of HIV-seropositive children in LMIC countries
      were receiving treatment, in part because of persisting low rates of diagnosis.
      This study of the prevalence and characteristics of children tested for HIV was
      embedded in the Coping with HIV/AIDS in Tanzania (CHAT) study in which HIV
      seropositive and HIV-seronegative adults, and adults with unknown HIV status were
      asked about HIV testing for their children. Data were gathered from November 2009
      to August 2010 during the scale-up of Prevention of Mother To Child Transmission
      and Early Infant Diagnosis programs in the region. Reports on 1776 children
      indicate that 31.7% of all children were reported to have been tested, including
      only 42.9% of children with an HIV-seropositive caregiver. In general, children
      more likely to be HIV tested were biological children of study participants,
      younger, of widowed adults, living in urban areas, and of HIV-seropositive
      parents/caregivers. Children belonging to the two indigenous tribes, Chagga and
      Pare, were more likely to be tested than those from other tribes. Rates of
      testing among children less than two years old were low, even for the HIV
      seropositive caregiver group. The persistence of low testing rates is discussed
      in terms of the accessibility and acceptability of child testing in resource poor
      settings.

PMID- 23875967
TI  - Expanding the boolean logic of the prokaryotic transcription factor XylR by
      functionalization of permissive sites with a protease-target sequence.
AB  - The sigma54-dependent prokaryotic regulator XylR implements a one-input/one
      output actuator that transduces the presence of the aromatic effector m-xylene
      into transcriptional activation of the cognate promoter Pu. Such a signal
      conversion involves the effector-mediated release of the intramolecular
      repression of the N-terminal A domain on the central C module of XylR. On this
      background, we set out to endow this regulator with additional signal-sensing
      capabilities by inserting a target site of the viral protease NIa in permissive
      protein locations that once cleaved in vivo could either terminate XylR activity
      or generate an effector-independent, constitutive transcription factor. To find
      optimal protein positions to this end, we saturated the xylR gene DNA with a
      synthetic transposable element designed for randomly delivering in-frame
      polypeptides throughout the sequence of any given protein. This Tn5-based system
      supplies the target gene with insertions of a selectable marker that can later be
      excised, leaving behind the desired (poly) peptides grafted into the protein
      structure. Implementation of such knock-in-leave-behind (KILB) method to XylR was
      instrumental to produce a number of variants of this transcription factor (TF)
      that could compute in vivo two inputs (m-xylene and protease) into a single
      output following a logic that was dependent on the site of the insertion of the
      NIa target sequence in the TF. Such NIa-sensitive XylR specimens afforded the
      design of novel regulatory nodes that entered protease expression as one of the
      signals recognized in vivo for controlling Pu. This approach is bound to
      facilitate the functionalization of TFs and other proteins with new traits,
      especially when their forward engineering is made difficult by, for example, the
      absence of structural data.

PMID- 23875968
TI  - Effectiveness of a cardiac surgery-specific transfusion protocol.
AB  - BACKGROUND: Cardiac surgery is often complicated by excessive bleeding that is
      commonly treated with blood products. In the year 2009 a transfusion protocol was
      introduced specifically designed for cardiac surgery procedures. This study aims
      to evaluate the effect of this protocol on transfusion of blood products and the
      occurrence of clinical events. STUDY DESIGN AND METHODS: This was a nonrandomized
      intervention study. The index group was transfused according to a tailor-made
      transfusion protocol (operation in 2009/2010) and the control group was
      transfused according to the Dutch national transfusion guideline (operation in
      2007/2008). The primary outcome was mean number of units transfused and
      proportion of patients transfused. Secondary outcomes were in-hospital mortality,
      myocardial infarction, cerebrovascular accident or transient ischemic attack,
      renal injury or failure, rethoracotomy, and prolonged mechanical ventilation.
      RESULTS: The control group comprised 2685 patients and the index group 2534
      patients. The tailor-made transfusion protocol resulted in a decrease of patients
      transfused with red blood cells (RBCs) and fresh-frozen plasma (FFP) during
      surgery with odds ratio of 0.69 (95% confidence interval [CI], 0.55-0.86) and
      0.63 (95% CI, 0.46-0.86), respectively. Fewer myocardial infarctions were
      observed in the index group with OR of 0.67 (95% CI, 0.47-0.96). CONCLUSION: The
      cardiac surgery-specific transfusion protocol resulted in fewer patients
      transfused with RBCs and FFP and a lower incidence of myocardial infarction. This
      tailor-made protocol has led to a more judicious use of blood products and is a
      basis for further refinement of coagulation management during cardiac surgery
      procedures.

PMID- 23875969
TI  - Altered steering strategies for goal-directed locomotion in stroke.
AB  - BACKGROUND: Individuals who have sustained a stroke can manifest altered
      locomotor steering behaviors when exposed to optic flows expanding from different
      locations. Whether these alterations persist in the presence of a visible goal
      and whether they can be explained by the presence of a perceptuo-motor disorder
      remain unknown. The purpose of this study was to compare stroke participants and
      healthy participants on their ability to control heading while exposed to
      changing optic flows and target locations. METHODS: Ten participants with stroke
      (55.6 +/- 9.3 yrs) and ten healthy controls (57.0 +/- 11.5 yrs) participated in a
      mouse-driven steering task (perceptuo-motor task) while seated and in a walking
      steering task. In the seated steering task, participants were instructed to head
      or 'walk' toward a target in the virtual environment by using a mouse while
      wearing a helmet-mounted display (HMD). In the walking task, participants
      performed a similar steering task in the same virtual environment while walking
      overground at their comfortable speed. For both experiments, the target and/or
      the focus of expansion (FOE) of the optic flow shifted to the side (+/-20 degrees
      ) or remained centered. The main outcome measure was net heading errors (NHE).
      Secondary outcomes included mediolateral displacement, horizontal head
      orientation, and onsets of heading and head reorientation. RESULTS: In the
      walking steering task, the presence of FOE shifts modulated the extent and timing
      of mediolateral displacement and head rotation changes, as well as NHE
      magnitudes. Participants overshot and undershot their net heading, respectively,
      in response to ipsilateral and contralateral FOE and target shifts. Stroke
      participants made larger NHEs, especially when the FOE was shifted towards the
      non-paretic side. In the seated steering task, similar NHEs were observed between
      stroke and healthy participants. CONCLUSIONS: The findings highlight the fine
      coordination between rotational and translational steering mechanisms in presence
      of targets and FOE shifts. The altered performance of stroke participants in
      walking but not in the seated steering task suggests that an altered perceptuo
      motor processing of optic flow is not a main contributing factor and that other
      stroke-related sensorimotor deficits are involved.

PMID- 23875970
TI  - Engineering biomaterial-associated complement activation to improve vaccine
      efficacy.
AB  - The complement system plays an important role in innate and adaptive immunity,
      which suggests that complement activation could be exploited as a potential
      strategy for vaccine adjuvants. Here we explored the potential of chitosan-based
      microparticles (CS-NH2 MPs) as a vaccine adjuvant with an active surface for
      complement activation due to the abundance of amino groups. In vaccination
      studies, using recombinant anthrax protective antigen as a model antigen,
      compared with the control microparticles (amino-cross-linked MPs), we found that
      microparticles (MPs) with abundant amino groups significantly enhanced higher
      antigen-specific IgG titers in vivo and enhanced the production of IL-4 and IFN
      gamma with ex vivo restimulation. Furthermore, proliferative responses of
      splenocytes to ex vivo antigen restimulation were enhanced following immunization
      with MPs with amino groups. Overall, these results indicated that CS-NH2 MPs with
      a high surface density of amino groups were favorable for complement activation
      and immune responses. Our data provide further design principles for studies on
      complement-activating MPs as a vaccine platform. 

PMID- 23875972
TI  - Mitotic kinesin Eg5 overcomes inhibition to the phase I/II clinical candidate
      SB743921 by an allosteric resistance mechanism.
AB  - Development of drug resistance during cancer chemotherapy is one of the major
      causes of chemotherapeutic failure for the majority of clinical agents. The aim
      of this study was to investigate the underlying molecular mechanism of resistance
      developed by the mitotic kinesin Eg5 against the potent second-generation
      ispinesib analogue SB743921 (1), a phase I/II clinical candidate. Biochemical and
      biophysical data demonstrate that point mutations in the inhibitor-binding pocket
      decrease the efficacy of 1 by several 1000-fold. Surprisingly, the structures of
      wild-type and mutant Eg5 in complex with 1 display no apparent structural changes
      in the binding configuration of the drug candidate. Furthermore, ITC and modeling
      approaches reveal that resistance to 1 is not through conventional steric effects
      at the binding site but through reduced flexibility and changes in energy
      fluctuation pathways through the protein that influence its function. This is a
      phenomenon we have called "resistance by allostery". 

PMID- 23875971
TI  - Epidemiological and molecular analysis of human norovirus infections in Taiwan
      during 2011 and 2012.
AB  - BACKGROUND: The human norovirus (NV) circulates worldwide and is a major cause of
      epidemics, which have increased in Taiwan since 2002. NV in acute gastroenteritis
      (AGE) and non-acute gastroenteritis (asymptomatic) patients, including children
      and adults, have not been previously examined in Taiwan; therefore, we examined
      the epidemiology and phylogeny of NV in AGE and asymptomatic patients of all
      ages. METHODS: 253 stool samples were collected from August 2011 to July 2012
      (including 155 AGE and 98 asymptomatic samples in Taiwan) and analyzed using
      reverse transcription-polymerase chain reaction (RT-PCR) for NV. Primers
      targeting the RNA-polymerase gene were used for RT-PCR to allow DNA sequencing of
      Taiwan NV strains and phylogenetic analyses. RESULTS: NV was detected in 24
      (9.5%) of 253 stool specimens using RT-PCR. NV was isolated from all age groups
      (1 to 86 y) and those NV-positive samples were major identified from inpatients
      (79.2%, 19/24). Statistical analysis showed that the NV infectious rate of AGE
      patients was statistically significant (P < 0.05) for age, season and water type,
      respectively. Phylogenetic analyses of the RdRp region sequence showed that 24 NV
      isolates belonged to Genogroup II Genotype 4 (GII.4). They were closely related
      to the epidemic strain in Taiwan in 2006, the GII.4-2006b pandemic strain in
      2006, and the GII.4-New Orleans strain in 2010. CONCLUSION: This study is the
      first to examine NV in sporadic AGE and asymptomatic patients in Taiwan.
      Furthermore, epidemic strains of isolated GII.4 were predominant in Taiwan during
      2011 and 2012.

PMID- 23875973
TI  - Protective reactivity and alteration of the brain tissue in alcoholics evidenced
      by SOD1, MMP9 immunohistochemistry, and electron microscopy.
AB  - Alcohol and its associated oxidative stress is one of the widespread contributors
      to the brain damage. Matrix metalloproteinases, which are extensively analyzed in
      brain pathology studies, are not sufficiently investigated in chronic alcohol
      consumption. This study evaluated regional brain damage caused by oxidative
      stress. Contribution of metalloproteinase-9 to this affection was evidenced in
      alcoholic subjects and correlated with ultrastructural changes. The authors found
      correlation between neuronal expression patterns of superoxide dismutase-1 and
      metalloproteinase-9 in nigral (r = 0.532, p < 0.001), striatal (r = 0.327, p <
      0.001), and cortical (r = 0.306, p < 0.001) regions, and a significant decrease
      of nigral superoxide dismutase-1 median values accompanied by severe myelin
      damage.

PMID- 23875974
TI  - The prostate-specific antigen test.
AB  - Before the 1980s, prostate cancer (PC) was considered a deadly disease. The
      mortality-incidence ratio showed that 1 out of each 2 - 3 PC patients died of
      this disease. On the other hand, autopsy studies have shown that latent PC is
      common in middle-aged men. The prostate-specific antigen (PSA), a glycoprotein
      produced by the epithelial cells of the prostate gland, received FDA's approval
      in 1986 for monitoring treatment response, and in 1994 as a screening aid for the
      diagnosis of PC. After the publication of two randomized trials on PC screening
      using the PSA test, it is generally accepted that systematic PSA-based screening,
      as compared to a clinical situation with virtually no screening, can reduce
      suffering from metastatic disease and PC mortality. However, what is also shown
      is that PSA-based screening coincides with a considerable amount of unnecessary
      testing and overdiagnosis. Should we abandon the use of the PSA test for the
      diagnosis of PC, or should we encourage PSA testing and make it freely available
      for all men at any time? Both the answers should be "No." What we must do is use
      the test as wisely as is currently possible and inform men, who want to be
      tested, in a balanced way about harms and potential benefits. 

PMID- 23875975
TI  - Variants within the COMP and THBS2 genes are not associated with Achilles
      tendinopathy in a case-control study of South African and Australian populations.
AB  - Cartilage oligomeric matrix protein is a structural protein of the extracellular
      matrix, while thrombospondin-2 is a matricellular protein involved in cell-matrix
      interactions. Recent studies have shown that genetic variation is a significant
      risk factor for Achilles tendinopathy, and the genes encoding cartilage
      oligomeric matrix protein (COMP) and thrombospondin-2 (THBS2) were identified as
      good candidate genes for association with Achilles tendinopathy. This study aimed
      to test the association of sequence variants within these candidate genes with
      the risk of Achilles tendinopathy in participants from South Africa (SA) and
      Australia (AUS). Three-hundred and forty (133 SA; 207 AUS) control participants
      with no history of Achilles tendinopathy and 178 (94 SA; 84 AUS) participants
      clinically diagnosed with Achilles tendinopathy were genotyped for five single
      nucleotide polymorphisms within the COMP and THBS2 genes in this case-control
      study. There was no difference in genotype distributions between control and
      tendinopathy groups for either the THBS2 variants rs9505888, rs6422747 and
      rs9283850, or the COMP variants rs730079 and rs28494505 in the SA and AUS
      populations. As the selection of COMP and THBS2 as candidate genes was hypothesis
      driven, based on biological function, the possibility that other variants within
      these genes are associated with Achilles tendinopathy cannot be excluded.

PMID- 23875976
TI  - Genetic assessment of safflower (Carthamus tinctorius L.) collection with
      microsatellite markers acquired via pyrosequencing method.
AB  - A genetic evaluation of safflower germplasm collections derived from different
      geographical regions and countries will provide useful information for
      sustainable conservation and the utilization of genetic diversity. However, the
      molecular marker information is limited for evaluation of genetic diversity of
      safflower germplasm. In this study, we acquired 509 putative genomic SSR markers
      for sufficient genome coverage using next-generation sequencing methods and
      characterized thirty polymorphic SSRs in safflower collection composed of 100
      diverse accessions. The average allele number and expected heterozygosity were
      2.8 and 0.386, respectively. Analysis of population structure and phylogeny based
      on thirty SSR profiles revealed genetic admixture between geographical regions
      contrary to genetic clustering. However, the accessions from Korea were
      genetically conserved in distinctive groups in contrast to other safflower gene
      pool. In conclusion, these new genomic SSRs will facilitate valuable studies to
      clarify genetic relationships as well as conduct population structure analyses,
      genetic map construction and association analysis for safflower. 

PMID- 23875977
TI  - Introduction to the issue of state sovereignty and humanitarian action.
AB  - There has been greater discussion among humanitarians in recent years about the
      rise in the number of 'strong states', and the suggestion has been made that
      states are increasingly reasserting their sovereignty. This introduction to this
      special issue of Disasters on 'State Sovereignty and Humanitarian Action'
      contends that it is not states that have changed, but rather the international
      framework that surrounds humanitarian action. The latter has altered so
      substantially that a fundamental gap has developed between states and
      international humanitarian actors in terms of describing what sovereignty entails
      and how it is expressed. At the heart of this dilemma are the urgent needs of
      people caught up in crises, whose well-being becomes the contested ground on
      which states and humanitarian actors clash. This paper explores the current and
      historical dimensions of these shifts, and provides a conceptual overview for
      this special issue. 

PMID- 23875978
TI  - Versatile fabrication of ultralight magnetic foams and application for oil-water
      separation.
AB  - Ultralow-density (<10 mg cm(-3)) materials have many important technological
      applications; however, most of them were fabricated using either expensive
      materials or complicated procedures. In this study, ultralight magnetic Fe2O3/C,
      Co/C, and Ni/C foams (with a density <5 mg cm(-3)) were fabricated on the
      centimeter scale by pyrolyzing commercial polyurethane sponge grafted with
      polyelectrolyte layers based on the corresponding metal acrylate at 400  degrees
      C. The ultralight foams consisted of 3D interconnected hollow tubes that have a
      diameter of micrometer and nanoscale wall thickness, forming hierarchical
      structures from macroscopic to nanometer length scales. More interesting was that
      the wall thickness and morphology of the microtubes could be tuned by controlling
      the concentrations of acrylic acid and metallic cations. After modification with
      low-surface-energy polysiloxane, the ultralight foams showed superhydrophobicity
      and superoleophilicity, which quickly and selectively absorbed a variety of oils
      from a polluted water surface under magnetic field. The oil absorption capacity
      reached 100 times of the foams' own weight, exhibiting one of the highest values
      among existing absorptive counterparts. By controlling the composition and
      conformation of the grafted polyelectrolyte layers, the present approach is
      extendable to fabricate a variety of ultralow-density materials desirable for
      absorptive materials, electrode materials, catalyst supports, etc. 

PMID- 23875979
TI  - Acute retinal necrosis associated with central retinal artery occlusion followed
      after its resolution by keratouveitis.

PMID- 23875980
TI  - Qualitative exploration of the relationship between HIV/AIDS patients'
      experiences of clinical services and treatment adherence at Maitama District
      Hospital, Abuja, Nigeria.
AB  - Nigeria has the third largest number of patients worldwide living with HIV/AIDs,
      and the Nigerian government has set ambitious targets to slow, halt and
      potentially reverse this number over the coming years. Clinical service provision
      has increased to meet this challenge, and yet it is unknown how services may
      affect patient anti-retroviral therapy (ART) adherence. The aim of this study was
      to learn from patients what factors influence their adherence, and how services
      could be changed to facilitate adherence. In-depth interviews were conducted with
      35 HIV patients attending Maitama District Hospital in Abuja and supplemented
      with shadowing observations of additional 10 patients during their clinic day
      appointment. Faith, stigma and discrimination and the hospital care patients
      received all influenced their thinking in relation to ART. Faith was expressed
      not only through their religious beliefs but also in the effectiveness of ART.
      They feared disclosure, even to close family, due to the stigma associated with
      HIV, and the threat of discrimination. They felt that the hospital service was
      under-resourced to cope with the volume of patients which led to delays on clinic
      day, including limited ART availability. This necessitated repeated hospital
      visits, thus increasing the chance of their status being revealed to third
      parties. Shadowing confirmed lengthy procedural delays in the hospital systems. 

PMID- 23875981
TI  - Public and policy maker support for point-of-sale tobacco policies in New York.
AB  - PURPOSE: To compare public and policy maker support for three point-of-sale
      tobacco policies. DESIGN: Two cross-sectional surveys--one of the public from the
      New York Adult Tobacco Survey and one of policy makers from the Local Opinion
      Leader Survey; both collected and analyzed in 2011. SETTING: Tobacco control
      programs focus on educating the public and policy makers about tobacco control
      policy solutions. SUBJECTS: Six hundred seventy-six county-level legislators in
      New York's 62 counties and New York City's five boroughs (response rate: 59%);
      7439 New York residents aged 18 or older. Landline response rates: 20.2% to 22%.
      Cell phone response rates: 9.2% to 11.1%. MEASURES: Gender, age, smoking status,
      presence of a child aged 18 years or younger in the household, county of
      residence, and policy maker and public support for three potential policy
      solutions to point-of-sale tobacco marketing. ANALYSIS: t-tests to compare the
      demographic makeup for the two samples. Adjusted Wald tests to test for
      differences in policy support between samples. RESULTS: The public was
      significantly more supportive of point-of-sale policy solutions than were policy
      makers: cap on retailers (48.0% vs. 19.2%, respectively); ban on sales at
      pharmacies (49.1% vs. 38.8%); and ban on retailers near schools (53.3% vs.
      42.5%). LIMITATIONS: cross-sectional data, sociodemographic differences, and
      variations in item wording. CONCLUSIONS: Tobacco control programs need to include
      information about implementation, enforcement, and potential effects on multiple
      constituencies (including businesses) in their efforts to educate policy makers
      about point-of-sale policy solutions.

PMID- 23875982
TI  - Achievement of exercise objectives and satisfaction with the walk with ease
      program-group and self-directed participants.
AB  - PURPOSE: This study presents group (instructor-led) and self-directed (nongroup)
      participant achievement of exercise objectives and satisfaction with the
      Arthritis Foundation's Walk With Ease (WWE) program at 6 weeks postintervention
      and 1-year follow-up. DESIGN: Secondary data analysis. SETTING: Rural and urban
      counties in North Carolina. SUBJECTS: Four hundred sixty-two adults with self
      reported joint pain/stiffness or physician-diagnosed arthritis, age >=18 years,
      no serious medical condition, no cognitive impairments, English speaking.
      Intervention. WWE is a 6-week community-based walking program offered in two
      formats-group and self-directed. MEASURES: Self-report measures collected at
      baseline, 6 weeks, and 1 year. ANALYSIS: Descriptive statistics, chi (2) and t
      tests. RESULTS: Individuals self-selected either group (n = 192) or self-directed
      (n = 270) format. On average, participants were age 67, Caucasian (70%), and
      female (88%). Mean minutes per walk increased from 16.7 at baseline to 34.2
      minutes at 1 year among group participants, and from 16.5 to 33.7 minutes among
      self-directed. At 1 year, 59.6% of group and 69.3% of self-directed participants
      reported continued walking (p = .06). Group participants were more likely than
      self-directed to do recommended stretching (p < .02) and warm-up/cool-down
      exercises (p < .01). CONCLUSION: Group and self-directed participants have
      similar self-reported walking outcomes but have some differences in their
      utilization of WWE recommendations.

PMID- 23875983
TI  - Interventions with children and parents to improve physical activity and body
      mass index: a meta-analysis.
AB  - OBJECTIVE: Examine the effect of interventions with parents and children on
      children's physical activity and body mass index (BMI). DATA SOURCE: Computerized
      searches for intervention studies published between 1990 and 2011 used multiple
      ProQuest databases, including unpublished dissertations and theses to minimize
      publication bias. STUDY INCLUSION AND EXCLUSION CRITERIA: English-language,
      intervention-testing studies of children, parents, or families with outcomes of
      physical activity or BMI were retrieved from peer-reviewed journals,
      dissertations, and theses. Eliminated studies had no control or comparison group;
      had no continuous outcome variable; had no physical activity/exercise and/or BMI
      as outcomes; or had incomplete statistics necessary for meta-analysis (means,
      standard deviations, or confidence intervals). DATA EXTRACTION: Twenty-one
      studies met inclusion criteria. Quality criteria were control group, objective
      outcome variable measure, clarity of variable definitions, and number and reason
      for subject withdrawal. DATA SYNTHESIS: Meta-analysis on the raw difference of
      means estimated mean weighted effect size (MWES) assessed dispersion of effects
      and computed a summary effect. RESULTS: MWES for interventions with parents and
      children on physical activity (Z = 2.92; confidence interval [CI] = .09 to .48; p
      = .002) and on BMI for interventions with children alone (Z = -2.10; CI = -.16 to
      -.01; p = .02) was significant. CONCLUSION: A significant effect on physical
      activity but not on BMI was found when interventions included both parents and
      their children.

PMID- 23875984
TI  - Increased risk of very low birth weight, rapid postnatal growth, and autism in
      underweight and obese mothers.
AB  - PURPOSE: To determine whether prepregnancy weight was associated with children's
      birth weight, early physical growth, and autism diagnosis. DESIGN: Early
      Childhood Longitudinal Study-Birth Cohort data. SETTING: United States. SUBJECTS:
      Representative sample of U.S. children followed from birth through kindergarten
      (n = 4800). Also, a subpopulation of the very low birth weight children was
      examined (n = 500). MEASURES: Maternal variables included age and prepregnancy
      body mass index. Changes in children's height, weight, and head circumference
      between 9 months and 2 years were used as growth metrics. Children's sex, age,
      birth weight, and reported autism were also considered. ANALYSIS: Logistic and
      multinomial logistic models assessed the impact of prepregnancy weight on birth
      weight and children's subsequent rate of physical growth and autism. RESULTS:
      Children born to underweight or obese mothers had increased odds of very low
      birth weight. Very low birth weight was related to rapid height and weight growth
      and more than twice the likelihood to subsequently be diagnosed with autism. For
      the subgroup of very low birth weight children, rapid head growth was related to
      a fivefold increase in the odds of autism. After accounting for the impact birth
      weight and growth rates, we found prepregnancy weight indirectly impacted autism
      risk. CONCLUSION: Being underweight or obese during prepregnancy indirectly
      increased risk for autism from increased odds of low birth weight and accelerated
      postnatal growth.

PMID- 23875985
TI  - Association of street connectivity and road traffic speed with park usage and
      park-based physical activity.
AB  - PURPOSE: The purpose of this study was to examine associations between street
      connectivity and road traffic speed and neighborhood residents' use of parks and
      park-based physical activity. DESIGN: Cross-sectional. SETTING: Kansas City,
      Missouri. SUBJECTS: Participants were 893 adults from randomly selected
      households. MEASURES: Both self-reported park use and park-based physical
      activity were dichotomized as some versus none. Intersection density was
      calculated around each participant, and network analysis was used to determine
      whether participants had to travel on or cross a road with traffic speed greater
      than 35 miles per hour (mph) to reach the closest park. ANALYSIS: Multilevel
      logistic regression examined the association between intersection density and
      traffic speed wit park use and park-based physical activity. RESULTS: Compared to
      those in the lowest intersection density quartile, participants in the third and
      fourth quartiles were more likely to use parks and to engage in physical activity
      in parks (odds ratio [OR] = 1.76-2.34; all p < .05). Likewise, compared to those
      who had a high-speed road on their way to the closest park, participants with
      slower traffic routes to parks were more likely to use the parks (OR = 1.47; 95%
      confidence interval [CI] = 1.05-1.92). CONCLUSION: In addition to park proximity
      and the design of park features, ensuring direct and safe access to parks through
      street network design and traffic speed reduction strategies may be key to
      facilitating park-related physical activity.

PMID- 23875986
TI  - Social entrepreneurship in religious congregations' efforts to address health
      needs.
AB  - PURPOSE: Examine how religious congregations engage in social entrepreneurship as
      they strive to meet health-related needs in their communities. DESIGN: Multiple
      case studies. SETTING: Los Angeles County, California. PARTICIPANTS: Purposive
      sample of 14 congregations representing diverse races/ethnicities (African
      American, Latino, and white) and faith traditions (Jewish and various Christian).
      METHOD: Congregations were recruited based on screening data and consultation of
      a community advisory board. In each congregation, researchers conducted
      interviews with clergy and lay leaders (n = 57); administered a congregational
      questionnaire; observed health activities, worship services, and neighborhood
      context; and reviewed archival information. Interviews were analyzed by using a
      qualitative, code-based approach. RESULTS: Congregations' health-related
      activities tended to be episodic, small in scale, and local in scope. Trust and
      social capital played important roles in congregations' health initiatives,
      providing a safe, confidential environment and leveraging resources from-and for
      faith-based and secular organizations in their community networks. Congregations
      also served as "incubators" for members to engage in social entrepreneurship.
      CONCLUSION: Although the small scale of congregations' health initiatives suggest
      they may not have the capacity to provide the main infrastructure for service
      provision, congregations can complement the efforts of health and social
      providers with their unique strengths. Specifically, congregations are
      distinctive in their ability to identify unmet local needs, and congregations'
      position in their communities permit them to network in productive ways.

PMID- 23875987
TI  - The impact of cessation media messages on cessation-related outcomes: results
      from a national experiment of smokers.
AB  - PURPOSE: Examine effects of exposure to two types of cessation advertisements on
      changes in cessation-related outcomes. DESIGN: Experimental data from a
      nationally representative, longitudinal sample of smokers, collected in three
      waves over 4 weeks. SETTING: National. Subjects. Three thousand and two adult
      U.S. smokers aged 18+ completed baseline and follow-up interviews at 2 and 4
      weeks, from December 2010 to February 2011. INTERVENTION: Six randomly assigned
      conditions consisting of repeated exposure to cessation advertisements: why-to
      quit advertisements featuring emotional, personal testimonies (1: WTQ-T) or
      graphic images (2: WTQ-G); how-to-quit advertisements (3: HTQ), a combination of
      both (4: WTQ-T + HTQ; 5: WTQ-G + HTQ), and no-ad condition (6: control).
      MEASURES: Cessation-related beliefs, attitudes, intentions, and quitting
      behavior. ANALYSIS: Multivariable ordinary least squares and logistic regressions
      testing whether exposure to antitobacco television advertisements were associated
      with changes in tobacco-related outcomes. RESULTS: Exposure to WTQ-T or WTQ-G
      advertisements, both alone and combined with HTQ advertisements, elicited
      positive change in beliefs, attitudes, and intentions as compared to controls.
      Smokers in three of four WTQ conditions were substantially more likely to have
      quit smoking at 4 weeks than controls (odds ratios range from 5.9 to 10.1, p <
      .05 or better). No effects were found for the HTQ-only condition. CONCLUSION:
      Exposure to WTQ advertisements markedly increases the odds that a smoker will
      quit in the study period, suggesting positive movement toward successful, long
      term cessation. HTQ advertisements did not enhance advertising effectiveness and
      may not be suitable as a primary message strategy.

PMID- 23875988
TI  - Valid and invalid accelerometry data among children and adolescents: comparison
      across demographic, behavioral, and biological variables.
AB  - PURPOSE: To examine whether there are differences between demographic,
      behavioral, and biological variables for those with invalid accelerometry data
      (IAD) and those with valid accelerometry data (VAD). DESIGN: Cross-sectional.
      SETTING: Data from 2003-2006 National Health and Nutrition Examination Survey
      (NHANES) were used. SUBJECTS: Participants included 1,315 children (i.e., 6-11
      years) with VAD and 534 children with IAD and 1,859 adolescents (i.e., 12-17
      years) with VAD and 1,057 with IAD. MEASURES: Physical activity (PA) was measured
      using an accelerometer, with questionnaires used to assess demographic and
      behavioral variables and biological parameters assessed from a blood sample.
      ANALYSIS: Wald and design-based likelihood ratio tests and logistic regression
      were used to assess differences between those subjects with IAD and those with
      VAD. RESULTS: After adjustments, overweight children, compared to normal weight
      children, were 1.6 (odds ratio [OR] = 1.67; 95% confidence interval [CI]: 1.22
      2.29) times more likely to have IAD. After adjustments, and as an example,
      adolescents engaging in 4 or more hours of computer use per day, compared to no
      computer use, were 2.6 (OR = 2.6; 95% CI: 1.38-5.18) times more likely to have
      IAD. CONCLUSION: Excluding youth with IAD may introduce bias, limit
      generalizability, and ultimately underestimate the association between PA and
      health outcomes. Future research is needed to identify reasons for poor
      monitoring compliance.

PMID- 23875989
TI  - Maximizing retention with high risk participants in a clinical trial.
AB  - PURPOSE: To describe effective retention strategies in a clinical trial with a
      high risk, low-income, and vulnerable patient population with serious mental
      illness. DESIGN: Follow-up assessments were conducted for a randomized clinical
      tobacco treatment trial at 3, 6, and 12 months postbaseline. Initial follow-up
      rates of <40% at 3 months led to implementation of proactive retention strategies
      including obtaining extensive contact information; building relationships with
      case managers and social workers; contacting jails and prisons; text messaging, e
      mailing, and messaging via social networking sites; identifying appointments via
      electronic medical record; and field outreach to treatment facilities,
      residences, and parks. SETTING: Large urban public hospital. SUBJECTS:
      Participants were current smokers recruited from 100% smoke-free locked
      psychiatry units. MEASURES: Assessments covered demographics, substance use, and
      mental health functioning. ANALYSIS: Retention rates were plotted over time in
      relation to key retention strategies. Chi-square and t-tests were used to examine
      participant predictors of retention at each follow-up. At the 12-month follow-up,
      the retention strategies that most frequently led to assessment completion were
      identified. RESULTS: The sample (N = 100) was 65% male; age x = 39.5 years (SD =
      11.3); 44% non-Hispanic white; 46% on Medicaid and 34% uninsured; 79% unemployed;
      and 48% unstably housed. Proactive retention strategies dramatically increased
      follow-up rates, concluding at 3 months = 82.65%, 6 months = 89.69%, and 12
      months = 92.78%. Married and divorced/separated/widowed participants, those with
      higher income, and participants with alcohol or illicit drug problems had
      increased retention from 3- to 12-month follow-up. CONCLUSION: Follow-up rates
      improved as proactive methods to contact participants were implemented. Dedicated
      research staff, multiple methods, community networking, and outreach within drug
      treatment settings improved retention.

PMID- 23875990
TI  - Impact of recess interventions on children's physical activity--a meta-analysis.
AB  - OBJECTIVE: The purpose of this paper was to explore the effect of recess
      interventions on children's physical activity (PA) levels and to examine which
      specific interventions/characteristics have more influence on children's PA. DATA
      SOURCE: Academic Search Premier, CINAHL, ERIC, MEDLINE, ProQuest, SPORT Discus.
      STUDY INCLUSION AND EXCLUSION CRITERIA: Papers published between 1986 and 2012,
      published in the English language, and evaluating any recess intervention with PA
      as an outcome. DATA EXTRACTION: Study outcomes were distilled into seven domains
      related to PA: age, gender, intervention type, intervention duration, duration of
      PA per intervention session, outcome measures, and study region. DATA SYNTHESIS:
      Effect sizes were pooled within and across studies for each domain separately.
      Moderator analyses were performed using gender, age, and total length of
      intervention. Twenty-three independent samples were provided from 13 studies.
      RESULTS: The estimated overall effect size for time in PA was .56 (SE .07),
      suggesting a positive and significant mean difference between pretest and
      posttest PA time after implementing a recess intervention. Differences in PA
      levels were moderated by age, duration and type of intervention, and type of
      outcome measures. CONCLUSION. The limited evidence suggests recess interventions
      can improve youth PA levels. Implications reinforce the importance of schools in
      advocating for recess during the school day. Strategies shown to increase student
      PA during recess should be implemented.

PMID- 23875991
TI  - Housekeeping gene expression stability in reproductive tissues after mitogen
      stimulation.
AB  - BACKGROUND: Intrauterine infection during pregnancy can trigger a local
      inflammatory response leading to several complications, such as preterm labor.
      Many studies have used in vitro and in vivo models employing mitogens to induce
      the expression of the characteristic proinflammatory mediators triggered by
      infection. However, relative expression assays depend on the stability of
      housekeeping gene expression, which can vary depending on certain stimuli. In
      this study, we analyzed the stability and pairwise variation in the expression of
      GAPDH, ACTB and RNA18S1 in cultured reproductive tissues under mitogen
      stimulation. We used fetal membranes, placental villous and umbilical cord
      explants from patients with normal term pregnancies (>37 weeks of gestation), as
      well as myometrium and cervix explants from patients undergoing hysterectomies.
      Tissues were stimulated with lipopolysaccharide or phytohemagglutinin for 24
      hours. We then analyzed the expression stability and the pairwise variation of
      GAPDH, ACTB and RNA18S1 from real time quantitative RT-PCR absolute threshold
      cycles (Cp) using geNorm software. RESULTS: In all of the tissues, the three
      housekeeping genes showed great stability under our experimental conditions.
      Pairwise variation analyses showed that only two reference genes are required for
      adequate normalization, GAPDH and ACTB being optimal in the cervix, fetal
      membranes and umbilical cord, while GAPDH and RNA18S1 are best for normalization
      in the placenta and myometrium. CONCLUSION: Our results show that GAPDH, ACTB and
      RNA18S1 are adequate references for gene expression normalization in reproductive
      tissues stimulated with mitogens in culture.

PMID- 23875992
TI  - Role of insulin and adenosine in the human placenta microvascular and
      macrovascular endothelial cell dysfunction in gestational diabetes mellitus.
AB  - Microvascular and macrovascular endothelial function maintains vascular
      reactivity. Several diseases alter endothelial function, including hypertension,
      obesity, and diabetes mellitus. In addition, micro- and macrovascular endothelial
      dysfunction is documented in GDM with serious consequences for the growing fetus.
      Increased l-arginine uptake via hCAT-1 and NO synthesis by eNOS is associated
      with GDM. These alterations are paralleled by activation of purinergic receptors
      and increased umbilical vein, but not arteries blood adenosine accumulation. GDM
      associates with NO-reduced adenosine uptake in placental endothelium, suggested
      to maintain and/or facilitate insulin vasodilation likely increasing hCAT-1 and
      eNOS expression and activity. It is proposed that increased umbilical vein blood
      adenosine concentration in GDM reflects a defective metabolic state of human
      placenta. In addition, insulin recovers GDM-alterations in hCAT-1 and eNOS in
      human micro- and macrovascular endothelium, and its biological actions depend on
      preferential activation of insulin receptors A and B restoring a normal-like from
      a GDM-like phenotype. We summarized existing evidence for a potential role of
      insulin/adenosine/micro- and macrovascular endothelial dysfunction in GDM. These
      mechanisms could be crucial for a better management of the mother, fetus and
      newborn in GDM pregnancies. 

PMID- 23875994
TI  - Sink or surf: atmospheric implications for succinic acid at aqueous surfaces.
AB  - Small organic compounds are increasingly being invoked as important players in
      atmospheric processes that occur on aerosol surfaces. The diacid succinic acid is
      one such constituent that is prevalent in the troposphere, surface active, and
      also water-soluble. This article presents a thorough examination of the surface
      characteristics of succinic acid at the vapor/water interface using a combination
      of theoretical simulation and experiments using vibrational sum frequency
      spectroscopy and surface tension. The adsorption and orientation of succinic acid
      at the water surface is characterized for a series of aqueous solution
      compositions relevant to atmospheric conditions. Fully protonated succinic acid
      is found to be particularly surface active. A new computational technique is
      introduced that provides a detailed picture of the different surface species that
      are contributing to the experimentally derived spectroscopic measurements.
      Additional results are presented for how SO2, a copollutant of succinic acid in
      the atmosphere, behaves at a water surface in the presence of surface adsorbed
      succinic acid. 

PMID- 23875993
TI  - Factors affecting hospital length of stay and hospital charges associated with
      road traffic-related injuries in Iran.
AB  - BACKGROUND: Road traffic injuries (RTIs) are a substantial cause of mortality and
      disability globally. There is little published information regarding healthcare
      resource utilization following RTIs, especially in low and middle-income
      countries (LMICs). The aim of this study was to assess total hospital charges and
      length of stay (LOS) associated with RTIs in Iran and to explore the association
      with patients' socio-demographic characteristics, insurance status and injury
      related factors (e.g. type of road users and safety equipment). METHOD: The study
      was based on the Iranian National Trauma Registry Database (INTRD), which
      includes data from 14 general hospitals in eight major cities in Iran, for the
      years 2000 to 2004. 8,356 patients with RTI admitted to the hospitals were
      included in the current study. The variables extracted for the analysis included
      total hospital charges and length of stay, age, gender, socio-economic and
      insurance status, injury characteristics, medical outcome and use of safety
      equipment among the patients. Univariable analysis using non-parametric methods
      and multivariable regression analysis were performed to identify the factors
      associated with total hospital charges and LOS. RESULTS: The mean hospital
      charges for the patients were 1,115,819 IRR (SD=1,831,647 IRR, US$128 +/-
      US$210). The mean LOS for the patients was 6.8 (SD =8 days). Older age, being a
      bicycle rider, higher injury severity and longer LOS were associated with higher
      hospital charges. Longer LOS was associated with being male, having lower
      education level, having a medical insurance, being pedestrian or motorcyclist,
      being a blue-collar worker and having more severe injuries. The reported use of
      safety equipment was very low and did not have significant effect on the hospital
      charges and LOS. CONCLUSION: The study demonstrated that the hospital charges and
      LOS associated with RTI varied by age, gender, socio-economic status, insurance
      status, injury characteristics and health outcomes of the patients. The results
      of the study provide information that can be of importance in the planning and
      design of road traffic injury control strategies.

PMID- 23875995
TI  - Molecular toxicity identification evaluation (mTIE) approach predicts chemical
      exposure in Daphnia magna.
AB  - Daphnia magna is a bioindicator organism accepted by several international water
      quality regulatory agencies. Current approaches for assessment of water quality
      rely on acute and chronic toxicity that provide no insight into the cause of
      toxicity. Recently, molecular approaches, such as genome wide gene expression
      responses, are enabling an alternative mechanism based approach to toxicity
      assessment. While these genomic methods are providing important mechanistic
      insight into toxicity, statistically robust prediction systems that allow the
      identification of chemical contaminants from the molecular response to exposure
      are needed. Here we apply advanced machine learning approaches to develop
      predictive models of contaminant exposure using a D. magna gene expression data
      set for 36 chemical exposures. We demonstrate here that we can discriminate
      between chemicals belonging to different chemical classes including endocrine
      disruptors and inorganic and organic chemicals based on gene expression. We also
      show that predictive models based on indices of whole pathway transcriptional
      activity can achieve comparable results while facilitating biological
      interpretability. 

PMID- 23875996
TI  - A "shocking" case rectified.

PMID- 23875997
TI  - Transvaginal natural orifice transluminal endoscopic surgery for adnexal masses.
AB  - AIM: Natural orifice transluminal endoscopic surgery (NOTES) is currently a very
      important topic for surgeons. This study aimed to describe the initial clinical
      experience of transvaginal NOTES for adnexal masses and investigate its
      feasibility and surgical outcome. METHODS: We performed transvaginal NOTES in
      seven patients with adnexal masses through a 2-cm incision in the posterior
      vaginal fornix. A transvaginal NOTES system comprising a wound protractor and a
      surgical glove with sheaths was used. Resection was performed according to the
      method of standard laparoscopic adnexal surgery. The adnexal mass was removed via
      the incision of the posterior vaginal fornix after complete resection. RESULTS:
      Since June 2011, seven patients have undergone transvaginal NOTES for adnexal
      masses. All cases were completed successfully without conversion to standard
      laparoscopic approach. The median age of the patients was 48 years (range, 36-60)
      and the median body mass index was 23.6 (range, 20.4-25.3). The median tumor size
      was 6 cm (range, 3.7-6.7). The median operative time was 45 min (range, 40-80).
      The estimated blood loss was minimal (range, 5-300 mL). The median postoperative
      hospital stay was 2 days (range, 1-3). No postoperative complications were
      observed at follow-up. All the patients were very satisfied with the cosmetic
      result. CONCLUSION: The findings show transvaginal NOTES with our method to be a
      feasible, safe and effective surgical technique that results in excellent
      cosmesis. It may be an alternative technique for the treatment of properly
      selected female patients with adnexal masses. More experience and instrumental
      improvement suitable for transvaginal NOTES are needed.

PMID- 23875998
TI  - p53 death signal is mainly mediated by Nuc1(EndoG) in the yeast Saccharomyces
      cerevisiae.
AB  - The tumor suppressor p53 plays a central role in the regulation of cellular
      growth and apoptosis. In the yeast Saccharomyces cerevisiae, the overexpression
      of the human p53 leads to growth inhibition and apoptotic cell death on minimal
      medium. In the present work, we show that p53-expressing cells are more
      susceptible to cell death after an apoptotic stimulus such as H2O2. The analysis
      of mutants involved in yeast apoptosis-like death suggests that the observed cell
      death is Yca1 independent and mainly mediated through Nuc1p.

PMID- 23875999
TI  - Validation of a Chinese version of the Quality of Well-Being Scale-Self
      Administered (QWB-SA) in patients with epilepsy.
AB  - PURPOSE: Generic preference-based health-related quality of life (HRQoL)
      instruments are increasingly used to estimate the quality-adjusted life years
      (QALYs) in cost-effectiveness/utility studies. However, no such tool has been
      used and validated in epilepsy patients in China. This study was conducted to
      validate a generic preference-based HRQoL instrument, namely the Quality of Well
      Being Scale-Self-Administered (QWB-SA) in Chinese patients with epilepsy.
      METHODS: Accepted translation procedures were followed to develop the Chinese QWB
      SA. An epilepsy group (adults with established diagnosis of epilepsy) and a
      control group (adults without manifested cognitive problems) were recruited
      between July and October, 2012, from two tertiary hospitals in China. After
      giving informed consent, each subject completed both the QWB-SA and the EuroQol
      (EQ-5D) as well as provided sociodemographic data. Construct validity was
      examined by six (convergent) and two (discriminative) a priori hypotheses.
      Sensitivity was compared by ability to differentiate epilepsy-specific variable
      based subgroups. Agreement between the QWB-SA and EQ-5D was assessed by
      intraclass correlation coefficient (ICC) and Bland-Altman plot. KEY FINDINGS: One
      hundred forty-four epilepsy patients and 323 control subjects were enrolled,
      respectively. The utility medians (interquartile range, IQR) for the QWB-SA and
      EQ-5D were 0.673 (0.172), 0.848 (0.275) for epilepsy group and 0.775 (0.258),
      1.000 (0.152) for control group, respectively. The difference in utilities
      between the two measures were significant (p < 0.0001). Construct validity was
      demonstrated by six a priori hypotheses. In addition, the QWB-SA was able to
      discriminate across different seizure frequency and antiepileptic drug (AED)
      treatment subgroups. Agreement between the QWB-SA and EQ-5D was demonstrated by
      ICC (0.725). Finally, the multiple linear regression analysis indicated that
      group and the EQ-VAS had influences on the utility difference of these two
      measures, whereas seizure frequency and number of AEDs were predictors of HRQoL
      as measured by the QWB-SA. SIGNIFICANCE: The QWB-SA is a valid and sensitive
      HRQoL measure in Chinese patients with epilepsy. Compared to the EQ-5D, the QWB
      SA showed superiority in coverage of health dimensions, sensitivity, and ceiling
      effects. However, future study is still needed to ascertain its responsiveness.

PMID- 23876000
TI  - Family and friends' fears of recurrence: impact on the patient's recovery after
      subarachnoid hemorrhage.
AB  - OBJECT: Patients with subarachnoid hemorrhage (SAH) and their close friends and
      family may be excessively fearful that the patient will have a recurrence, and
      such fears could play a critical role in the poor recovery shown by many patients
      The authors examined whether these fears could account for significant variance
      in psychosocial outcomes. METHODS: The authors prospectively studied a sample of
      69 patients with SAH alongside their spouse, other family member, and/or close
      friend identified as their significant other (SO). The patient/SO pairs were
      assessed at 13 months postictus for their fears of recurrence and for health
      related quality of life on the 8 domains of the 36-Item Short Form Health Survey.
      RESULTS: The SOs were found to be significantly more fearful of SAH recurrence
      than the patients. The SO's fears also explained unique variance in the patient's
      recovery on 4 of the 36-Item Short Form Health Survey domains over and above the
      patient's own fears, demographic and/or neurological variables, and the patient's
      history of psychiatric or neurological problems. The domains affected reflected
      activity-based and functional aspects of the patient's quality of life as opposed
      to more general characteristics of their emotional well-being or physical health
      state. CONCLUSIONS: The patient's recovery may be compromised if their spouse,
      close family, and/or friends are excessively fearful about their suffering a
      recurrence. Perhaps the SO's fears cause them to be overprotective of the patient
      and to restrict their day-to-day activities. Attention must therefore be given to
      the experience of having a loved one suffer from an SAH, and alleviating the
      caregiver's fears could help to promote a better outcome for the patient.

PMID- 23876001
TI  - MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of
      human non-small cell lung cancer cells.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer
      related mortality worldwide, and novel treatment modalities to improve the
      prognosis of patients with advanced disease are highly desirable. Oncolytic
      virotherapy is a promising approach for the treatment of advanced NSCLC.
      MicroRNAs (miRNAs) may be a factor in the regulation of tumor-specific viral
      replication. The purpose of this study was to investigate whether miRNA-145
      regulated oncolytic herpes simplex virus-1 (HSV-1) can selectively kill NSCLC
      cells with reduced collateral damage to normal cells. METHODS: We incorporated 4
      copies of miRNA-145 target sequences into the 3'-untranslated region of an HSV-1
      essential viral gene, ICP27, to create AP27i145 amplicon viruses and tested their
      target specificity and toxicity on normal cells and lung cancer cells in vitro.
      RESULTS: miRNA-145 expression in normal cells was higher than that in NSCLC
      cells. AP27i145 replication was inversely correlated with the expression of miRNA
      145 in infected cells. This oncolytic HSV-1 selectively reduced cell
      proliferation and prevented the colony formation of NSCLC cells. The combination
      of radiotherapy and AP27i145 infection was significantly more potent in killing
      cancer cells than each therapy alone. CONCLUSIONS: miRNA-145-regulated oncolytic
      HSV-1 is a promising agent for the treatment of NSCLC.

PMID- 23876002
TI  - In vivo self-assembly of fluorescent protein microparticles displaying specific
      binding domains.
AB  - In this study, fluorescent proteins (FPs) were engineered to self-assemble into
      protein particles inside recombinant Escherichia coli while mediating the display
      of various protein functionalities such as maltose binding protein or IgG binding
      domains of Protein A or G, respectively. Escherichia coli produced functional FP
      particles of up to 30% of cellular dry weight. The use of respective FP particles
      displaying certain binding domains in diagnostics and as bioseparation resins was
      demonstrated by direct comparison to commercial offerings. It was demonstrated
      that variable extensions (AVTS, FHKP, LAVG, or TS) of the N-terminus of FPs (GFP,
      YFP, CFP, HcRed) in combination with large C-terminal extensions such as
      translational fusion of the polyester synthase from Ralstonia eutropha or an
      aldolase from Escherichia coli led to extensive intracellular self-assembly of
      strongly fluorescent fusion protein particles of oval shape (0.5*1 MUm). The
      strong fluorescent label of these bioparticles in combination with covalent
      display of protein functions provides a molecular toolbox for the design of self
      assembled microparticles suitable for antibody-capture or ligand binding based
      diagnostic assays as well as the high affinity purification of target compounds
      such as antibodies.

PMID- 23876003
TI  - Use of Relief Contrast((r)) objective to improve sperm morphometric analysis by
      Isas((r)) casa system in the ram.
AB  - The aim of this study was to develop a new method for morphometric assessment of
      the sperm head and acrosome in the ram. Ejaculates from 10 adult males were
      collected using an artificial vagina. For each ejaculate, 10 semen smears were
      prepared, air-dried and divided (in pairs) into the following five treatment
      groups: (i) washed in distilled water and allowed to dry without further
      processing (DRY); (ii) fixed in 50% methanol (MET); (iii) fixed in 2%
      glutaraldehyde (GLUT); (iv) fixed and stained with Hemacolor((r)) (HEM) and (v)
      fixed and stained with SpermBlue((r)) (SB). The prepared slides were examined
      with a 40 * Relief Contrast((r)) objective (RC) and processed with ISAS((r))
      commercial software. The use of RC optics increased the contrast between acrosome
      and sperm head, allowing capture and morphometric analysis by ISAS of sperm heads
      and the acrosome, even in non-stained samples. MET and GLUT groups resulted in a
      lower number of acceptable, that is, correctly delineated, sperm heads than those
      in the SB, and SB and HEM groups, respectively (p < 0.05). The higher proportion
      of sperm discarded in MET and GLUT groups may be explained by a higher presence
      of artefacts. For the majority of the primary morphometric parameters of the
      sperm head and the acrosomal area, the relationship between treatments was the
      following: GLUT> HEM>= MET>= SB> DRY. When studying the proportion of the sperm
      head covered by the acrosome, the relation between treatments was: MET> DRY =
      GLUT = SB> HEM. It was concluded that the new method for sperm morphometric
      assessment allows the simultaneous assessment of sperm head and acrosome in the
      ram by the first time, even in unprocessed semen smears. 

PMID- 23876004
TI  - Absolute configuration of acremoxanthone C, a potent calmodulin inhibitor from
      Purpureocillium lilacinum.
AB  - Bioassay-guided fractionation of an extract prepared from the culture medium and
      mycelium of Purpureocillium lilacinum allowed the isolation of two calmodulin
      (CaM) inhibitors, namely, acremoxanthone C (1) and acremonidin A (2). The
      absolute configuration of 1 was established as 2R, 3R, 1'S, 11'S, and 14'R
      through extensive NMR spectroscopy and molecular modeling calculations at the DFT
      B3LYP/DGDZVP level, which included the comparison between theoretical and
      experimental specific rotation, 3J(C,H), and 3J(H,H) values. Compounds 1 and 2
      bind to the human calmodulin (hCaM) biosensor hCaM M124C-mBBr, with dissociation
      constants (Kd) of 18.25 and 19.40 nM, respectively, 70-fold higher than that of
      chlorpromazine (Kd = 1.24 MUM), used as positive control. Docking analysis using
      AutoDock 4.2 predicted that 1 and 2 bind to CaM at a similar site to that which
      KAR-2 binds, which is unusual. Furthermore, a novel, sensible, and specific
      fluorescent biosensor of hCaM, i.e., hCaM T110C-mBBr, was constructed; this
      device is labeled at a site where classical inhibitors do not interact and was
      successfully applied to measure the interaction of 1 with CaM. This is the first
      report of xanthone-anthraquinone heterodimers in species of Paecilomyces or
      Purpureocillium genera.

PMID- 23876006
TI  - Laterality of a second player position affects lateral deviation of basketball
      shooting.
AB  - Asymmetrically placed visual distractors are known to cause a lateral bias in the
      execution of a movement directed toward a target. The aim of the present
      experiment was to verify if the trajectory of the ball and the trajectory of the
      jump for a basket-shot can be affected by the sole position of a second player,
      who stays in front of the shooting player in one of three possible positions
      (centre, left or right) but too far to physically interfere with the shot. Young
      basketball players were asked to perform 60 shots at 6.25 m from a regular
      basket, with or without a second player staying in front of them in, alternately,
      a centre, left or right position. A computerised system measured the angular
      deviation of the jump direction from the vertical direction and the lateral
      deviation of the ball trajectory from the midline. The results showed that both
      the jump direction and the entry position of the ball deviated toward the
      opposite side from the second player's side; however, these effects were too
      small to significantly affect the mean goal percentage. This result confirms that
      some placements of the players can have an effect as visual distractors. Further
      studies are necessary to find what game conditions can make such distractors
      harmful for the athletic performance.

PMID- 23876007
TI  - Electron microscopy in kidney research: seeing is believing.
AB  - Electron microscopy (EM) has been an indispensable tool for kidney research since
      its inception more than half a century ago. Much of the substantial advances were
      propelled by the need to find methods to best visualize and analyze the kidney's
      structure deduced from the fundamental principle that has structure and function
      intimately related. The result of 3 decades of experimental kidney work between
      1950 and 1980 coincided with remarkable advances in nephrology that marked a
      renaissance era for renal pathology and resulted in the morphologic
      classification of medical kidney diseases. In the era of genetics and molecular
      medicine TEM continues to contribute significant clinical and pathogenetic
      insights in kidney disease. The basic principles as applied to kidney disease
      experimental models are discussed with emphasis on crescent formation in Col4A3
      deficient mice and a mouse model of experimental oxalosis (CaOx).

PMID- 23876008
TI  - Blood RNA biomarker panel detects both left- and right-sided colorectal
      neoplasms: a case-control study.
AB  - BACKGROUND: Colonoscopy is widely regarded to be the gold standard for colorectal
      cancer (CRC) detection. Recent studies, however, suggest that the effectiveness
      of colonoscopy is mostly confined to tumors on the left side of the colon
      (descending, sigmoid, rectum), and that the technology has poor tumor detection
      for right-sided (cecum, ascending, transverse) lesions. A minimally invasive test
      that can detect both left-sided and right-sided lesions could increase the
      effectiveness of screening colonoscopy by revealing the potential presence of
      neoplasms in the right-sided "blind spot". METHODS: We previously reported on a
      seven-gene, blood-based biomarker panel that effectively stratifies a patient's
      risk of having CRC. For the current study, we assessed the effectiveness of the
      seven-gene panel for the detection of left- and right-sided CRC lesions. Results
      were evaluated for 314 patients with CRC (left-sided: TNM I, 65; TNM II, 57; TNM
      III, 60; TNM IV, 17; unknown, 9. right-sided: TNM I, 28; TNM II, 29; TNM III, 38;
      TNM IV, 12; unknown, 1 and including two samples with both left and right
      lesions) and 328 control samples. Blood samples were obtained prior to clinical
      staging and therapy. Most CRC subjects had localized disease (stages I and II,
      58%); regional (stage III) and systemic (stage IV) disease represented 32% and
      9%, respectively, of the study population. RESULTS: The panel detected left-sided
      (74%, 154/208) and right-sided (85%, 92/108) lesions with an overall sensitivity
      of 78% (215/316) at a specificity of 66% (215/328). Treatable cancer (stages I to
      III) was detected with left-sided lesion sensitivity of 76% (138/182) and right
      sided sensitivity of 84% (80/95). CONCLUSION: This seven-gene biomarker panel
      detected right-sided CRC lesions across all cancer stages with a sensitivity that
      is at least equal to that for left-sided lesions. This study supports the use of
      this panel as the basis for a patient-friendly, blood-based test that can be
      easily incorporated into a routine physical examination in advance of colonoscopy
      to provide a convenient companion diagnostic and a pre-screening alert,
      ultimately leading to enhanced CRC screening effectiveness.

PMID- 23876009
TI  - Earlobe keloids: a pilot study of the efficacy of keloidectomy with core fillet
      flap and adjuvant intralesional corticosteroids.
AB  - BACKGROUND: Management of earlobe keloids is challenging because they are often
      resistant to treatment. The literature reports different treatment modalities
      with variable responses. Surgical excision with core fillet flap in combination
      with adjuvant intralesional steroid injection has not been thoroughly explored
      for keloid treatment, in spite of its positive therapeutic and cosmetic outcome.
      OBJECTIVES: To evaluate the clinical efficacy of keloidectomy with core fillet
      flap and adjuvant intralesional steroid injection in treating earlobe keloids.
      MATERIALS AND METHODS: Between 2004 and 2012, 21 earlobe keloids were treated
      using keloidectomy with core fillet flap and given intraoperative intralesional
      steroid injections. Follow-up was scheduled 2 weeks after the procedure and then
      monthly to administer intralesional steroid injections and to assess response,
      postoperative complications, recurrence, and objective and subjective
      satisfaction. RESULTS: The clinical outcome efficacy was 87.6%. Mean follow-up
      was 21.9 months. Immediate recurrence was 9.5%, with few complications
      encountered. Subjectively, 82.3% of the patients were highly satisfied.
      CONCLUSION: Keloidectomy with core fillet flap and adjuvant intralesional steroid
      therapy is an effective modality for the clinical management of earlobe keloids.
      This approach should be considered for the treatment of this difficult condition.

PMID- 23876010
TI  - Iron status and dietary iron intake of female blood donors.
AB  - BACKGROUND: The aim was to assess iron status and dietary iron intake in a sample
      of premenopausal female regular and new blood donors. STUDY DESIGN AND METHODS:
      Premenopausal women blood donors were invited to participate. Blood samples were
      analyzed for serum ferritin and hemoglobin. An iron checklist assessed dietary
      iron intake. Donors were classified as regular donors or new donors. RESULTS:
      Twenty-one new donors (mean [SD] age, 28.6 [6.0] years; body mass index [BMI],
      25.6 [4.5] kg/m(2) ) and 172 regular donors (mean age, 29.4 [5.5] years; BMI,
      24.7 [3.8] kg/m(2) ) participated. Fifty percent of regular donors and 24% of new
      donors had depleted iron stores (serum ferritin <15 MUg/L; difference p = 0.036).
      Dietary iron intake was higher in regular donors (mean [SE], 12.6 [0.7] mg/day)
      compared to new donors (9.9 [0.4] mg/day; p = 0.006). Eighty-five percent of
      regular donors and 79% of new donors met the estimated average requirement for
      iron. CONCLUSIONS: Despite the fact that most of these donors had an adequate
      dietary iron intake, more than half of the blood donors had depleted iron stores.
      Increasing dietary iron intake through supplements and/or dietary means is
      expected to be necessary to maintain adequate iron status in this group.

PMID- 23876011
TI  - International humanitarian actors and governments in areas of conflict:
      challenges, obligations, and opportunities.
AB  - For too long international humanitarian aid has neglected the primary
      responsibility of the state to assist and protect its citizens in times of
      disaster. A focus on the role of the state in contexts where governments are
      active parties to a conflict and are failing to live up to these responsibilities
      is difficult and underpins many of the recurring dilemmas of humanitarian action.
      The fundamental principles of humanitarian action should offer a framework for
      principled engagement with governments in situations of conflict but too often
      they are still interpreted as shorthand for ignoring governments. Using
      principles to inform engagement with both states and other international actors
      engaged in crises could provide a way forward. However, this would need to be a
      humanitarian agenda that engages with developing country governments, with non
      OECD (Organisation for Economic Co-operation and Development) donors, and with
      the stabilisation and security agendas of Western governments, and not one that
      attempts to ring-fence an ever-shrinking isolationist humanitarian space. 

PMID- 23876012
TI  - Safety of olanzapine use in adolescents.
AB  - INTRODUCTION: Olanzapine was the second first-line atypical antipsychotic
      medication approved by the Food and Drug Administration (FDA) for the treatment
      of adult schizophrenia and later approved for adolescent schizophrenia and
      bipolar disorder. Initial studies performed on adults demonstrated efficacy
      compared to placebo and a first-generation antipsychotic medication. Initial
      assessments in adolescents with schizophrenia demonstrated significant symptom
      reduction without movement disorder, but with weight gain. Later studies reported
      efficacy for bipolar disorder in teenagers, but with weight gain. The assessment
      of olanzapine safety in teenagers has shown substantial weight gain and metabolic
      measures. Because of equivalent efficacy to other atypical antipsychotic
      medications and the metabolic side-effects, olanzapine is often recommended as a
      second-use medication. AREAS COVERED: Studies of olanzapine use in adolescents
      with schizophrenia or bipolar disorder demonstrate significant reduction in
      symptoms while causing no movement disorder side-effects. There has been
      reduction in use of olanzapine with adolescents as newer atypical antipsychotics
      have emerged associated with less weight gain. EXPERT OPINION: Studies of
      olanzapine have demonstrated effectiveness in adolescents with a psychotic
      illness. Metabolic side-effects are a strong concern of the field and have led to
      the recommendation of using the medication in a secondary fashion.

PMID- 23876014
TI  - CD4/CD8 ratio in aqueous humor in Uveitis.

PMID- 23876015
TI  - Theoretical study of the O...Cl interaction in fluorinated dimethyl ethers
      complexed with a Cl atom: is it through a two-center-three-electron bond?
AB  - Theoretical investigations are carried out on the interaction between fluorinated
      dimethyl ethers (FDME, nF = 0-4) and the Cl atom. Short intermolecular O...Cl
      distances between 2.401 and 2.938 A reveal the formation of a new class of
      complexes. The interaction energies calculated with the G2(MP2) method range
      between -9.1 (nF = 4) and -26.0 (nF = 0) kJ/mol. The charge transfer occurring
      from the ethers to atomic Cl is moderate and ranges between 0.012 e (nF = 4) to
      0.188 e (nF = 0). The binding energies are linearly related to the proton
      affinity, to the charge transfer (CT) occurring in the molecular system and
      inversely proportional to the ionization potential and electron affinity (IP-EA)
      values. The CT and spin density data indicate substantial two-center-three
      electron O...Cl interaction in CH3OCH3...Cl and CH3OCH2F...Cl systems, whereas
      for highly fluorinated ethers the interaction is predominantly electrostatic in
      nature. The formation of the complex results in a contraction of the CH bonds,
      especially in the gauche position. The blue shifts of the C-H stretching
      vibrations calculated in the partially deuterated isotopomers range between 2 and
      54 cm(-1) and are correlated to the variation of the CH distances. 

PMID- 23876016
TI  - Fresh look at the mystery of magnetization reversal in YVO3.
AB  - Phase transitions and detailed magnetic properties of polycrystalline AP
      YVO3.00(1) (prepared at ambient pressure by a conventional solid-state method)
      and polycrystalline HP-YVO3.04(1) and HP-YVO3.05(1) (AP-YVO3 treated at 6 GPa and
      1600 K during 130 and 15 min, respectively) were investigated. The three samples
      showed a remarkable exchange bias (EB) effect. HP-YVO3.04 and HP-YVO3.05 had
      similar chemical composition, crystallographic parameters, and particle size, but
      their magnetic properties were qualitatively different. EB was negative at all
      temperatures in AP-YVO3 and HP-YVO3.05, resulting in the absence of magnetization
      reversal (MR). Positive EB was observed in HP-YVO3.04 between T(N2) = 71 K and T*
      = 88 K resulting in MR or negative magnetization between those temperatures. It
      was demonstrated that polycrystalline HP-YVO3.04 behaved similar to single
      crystals of YVO(3+delta). By the careful control of the trapped magnetic field,
      measurement conditions were found under which no MR occurred in HP-YVO3.04 at
      moderate magnetic fields, indicating that MR is not an intrinsic property of
      YVO(3+delta). A drastic effect of trapped magnetic fields on MR and memory
      effects were observed. The importance of an "insignificant" anomaly at T(FM) =
      140 K for MR was suggested. We also suggested that "positive exchange bias",
      "defects", "interfaces", and "pinning" should be keywords for understanding YVO3
      and probably other perovskite materials with the MR effect.

PMID- 23876013
TI  - Stretching and controlled motion of single-stranded DNA in locally heated solid
      state nanopores.
AB  - Practical applications of solid-state nanopores for DNA detection and sequencing
      require the electrophoretic motion of DNA through the nanopores to be precisely
      controlled. Controlling the motion of single-stranded DNA presents a particular
      challenge, in part because of the multitude of conformations that a DNA strand
      can adopt in a nanopore. Through continuum, coarse-grained and atomistic
      modeling, we demonstrate that local heating of the nanopore volume can be used to
      alter the electrophoretic mobility and conformation of single-stranded DNA. In
      the nanopore systems considered, the temperature near the nanopore is modulated
      via a nanometer-size heater element that can be radiatively switched on and off.
      The local enhancement of temperature produces considerable stretching of the DNA
      fragment confined within the nanopore. Such stretching is reversible, so that the
      conformation of DNA can be toggled between compact (local heating is off) and
      extended (local heating is on) states. The effective thermophoretic force acting
      on single-stranded DNA in the vicinity of the nanopore is found to be
      sufficiently large (4-8 pN) to affect such changes in the DNA conformation. The
      local heating of the nanopore volume is observed to promote single-file
      translocation of DNA strands at transmembrane biases as low as 10 mV, which opens
      new avenues for using solid-state nanopores for detection and sequencing of DNA. 

PMID- 23876017
TI  - Rutin (quercetin rutinoside) induced protein-energy malnutrition in chronic
      kidney disease, but quercetin acted beneficially.
AB  - Nutraceutically, much of the literature has indicated that an aglycon and its
      related glycoside would act similarly. However, controversial reports are
      accumulating. We hypothesize that rutin (RT) and quercetin (QT)
      pharmacodynamically could act differently. To confirm this, doxorubicin (DR) (8.5
      mg/kg) was used to induce rat chronic kidney disease (CKD) and then treated with
      QT and RT (each 70 mg/kg body weight per day) for 13 weeks. QT exhibited better
      body weight gaining effect (420 +/- 45) vs RT, 350 +/- 57 g/rat (p < 0.001). DR
      raised the ratio kidney-to-body weight (%) to 0.82 (p < 0.001) vs RT, 0.62 (p <
      0.01), and QT, 0.35 (p < 0.01). DR reduced the glomerular filtration rate to 25.2
      vs RT, 48 +/- 11.3; QT, 124.7 +/- 12.8 (p < 0.001) and the control, 191.5 +/-
      15.7 mL/h (p < 0.001). DRCKD reduced hematocrit to 29 +/- 5; RT, to 28 +/- 5 (p <
      0.05); QT, to 36 +/- 6 vs the control 37.5 +/- 4%, (p < 0.01). DRCKD reduced the
      serum albumin (s-Ab) to 2.1 +/- 0.2 (p < 0.001); QT, to 2.7 +/- 0.2 (p < 0.05) vs
      the normal 4.3 +/- 0.5 g/dL, yet RT was totally ineffective. DRCKD raised serum
      cholesterol level to 340 +/- 30; vs RT, 260 +/- 12; QT, 220 +/- 25; and the
      normal value, 70 +/- 25 mg/dL. DRCKD increased serum triglyceride to 260 +/- 15
      (p < 0.001), RT and QT restored it to 170 +/- 25 and 200 +/- 15 (p < 0.05) vs the
      normal 26-145 mg/dL. DRCKD elevated blood urea nitrogen to 38 +/- 3 vs RT, to 98
      +/- 6 mg/dL (p < 0.001), implicating "protein-energy malnutrition". RT stimulated
      serum creatinine (sCr) production to reach 6.0 +/- 0.9 mg/dL (p < 0.001). QT did
      not alter the sCr level. RT but not QT induced uremia and hypercreatininemia. DR
      significantly downregulated Bcl-2, but highly upregulated Bax, Bad, and cleaved
      caspase-3, implicating the intrinsic mitochondrial pathway. DR damaged DNA, but
      QT completely rescued such an effect and recovered renal amyloidosis and collagen
      deposition. Conclusively, RT and QT act differently, and RT is inferior to QT
      with respect to treating CKD. 

PMID- 23876018
TI  - Gene therapy briefs.

PMID- 23876019
TI  - Persistent benign oligemia causes CT perfusion mismatch in patients with
      intracranial large artery occlusive disease during subacute stroke.

PMID- 23876020
TI  - Adaptive pores: charge transfer modules as supramolecular handles for reversible
      pore engineering of mesoporous silica.
AB  - We introduce a non-covalent pore engineering approach to achieve exceptional
      reversibility of functionalization in SBA-15 through viologen-pyranine charge
      transfer (CT) modules. By employing alkyl derivatives of pyranine as donors, we
      could exploit the strong CT interactions between pyranine and viologen to
      reversibly modify the pore size and philicity. The fast binding of the donors
      enables quick and facile functionalization within minutes at room temperature.
      The modularity of the approach enables modification of pores with custom-designed
      compositions, components, and functions. The high selectivity exhibited by
      viologen on the pore wall facilitated its use in a CT affinity column. 

PMID- 23876021
TI  - In vitro comparison of the delivery of gaseous microemboli and hemodynamic energy
      for a diagonal and a roller pump during simulated infantile cardiopulmonary
      bypass procedures.
AB  - Cardiopulmonary bypass (CPB) is used for a variety of procedures in pediatric
      patients. Flow settings of the CPB pump have dramatic effects on patient outcome,
      and gaseous microemboli delivery within the CPB circuit has been linked to
      neurological complications. To ensure the ongoing improvement of pediatric CPB,
      consistent evaluation and improvement of the equipment is necessary. In this
      study we analyze the Jostra HL-20 roller pump (Jostra USA, Austin, TX, USA) and a
      Medos Deltastream DP3 diagonal pump (MEDOS Medizintechnik AG, Stolberg, Germany)
      which has not yet received Food and Drug Administration approval. An infant CPB
      model with heparinized human blood is used to quantify the gaseous microemboli
      delivery (via an Emboli Detection and Classification Quantifier), as well as the
      hemodynamic energy delivered under flow rates of 400, 800, and 1200 mL/min.
      Results show that at most flow settings the DP3 delivers fewer microemboli than
      the Jostra roller pump at the pre-oxygenator site, with an exception at 1200
      mL/min under pulsatile mode. The total volume and the number of gaseous
      microemboli greater than 40 MUm in diameter were lower in the DP3 group. The HL
      20 exhibits less stolen blood flow (except at 1200 mL/min) and oxygenator
      pressure drops in both pulsatile and nonpulsatile mode. Additionally, under
      pulsatile flow the DP3 delivers greater surplus hemodynamic energy. Both pumps
      produce relatively few microemboli and deliver adequate hemodynamic energy to the
      pseudo-patient, with the DP3 performing slightly better under most flow settings.

PMID- 23876022
TI  - Online detection of concerned HIV-related messages in web forums.
AB  - Web forums become the means of online communication and information sharing
      sources for the learning about health care and related treatment knowledge. By
      adopting web crawlers and natural language processing techniques, the automatic
      identification approach of the concerned HIV-related messages is proposed to
      facilitate the health authorities and social support groups in instant
      counseling. The proposed supervised GA/k-means for classification approach can
      help construct an effective identification and classification model with
      acceptable classification performance accompanied with its full flexibility to
      develop different fitness functions in accordance with the need of different
      requirements. Furthermore, with the aid of correspondence analysis, the most
      frequently used terms in concerned HIV-related messages are identified and focus
      on risky sexual behavior whereas unconcerned messages are those who of worried
      well.

PMID- 23876023
TI  - Retrospective record review in proactive patient safety work - identification of
      no-harm incidents.
AB  - BACKGROUND: In contrast to other safety critical industries, well-developed
      systems to monitor safety within the healthcare system remain limited.
      Retrospective record review is one way of identifying adverse events in
      healthcare. In proactive patient safety work, retrospective record review could
      be used to identify, analyze and gain information and knowledge about no-harm
      incidents and deficiencies in healthcare processes. The aim of the study was to
      evaluate retrospective record review for the detection and characterization of no
      harm incidents, and compare findings with conventional incident-reporting
      systems. METHODS: A two-stage structured retrospective record review of no-harm
      incidents was performed on a random sample of 350 admissions at a Swedish
      orthopedic department. Results were compared with those found in one local, and
      four national incident-reporting systems. RESULTS: We identified 118 no-harm
      incidents in 91 (26.0%) of the 350 records by retrospective record review. Ninety
      four (79.7%) no-harm incidents were classified as preventable. The five incident
      reporting systems identified 16 no-harm incidents, of which ten were also found
      by retrospective record review. The most common no-harm incidents were related to
      drug therapy (n = 66), of which 87.9% were regarded as preventable. CONCLUSIONS:
      No-harm incidents are common and often preventable. Retrospective record review
      seems to be a valuable tool for identifying and characterizing no-harm incidents.
      Both harm and no-harm incidents can be identified in parallel during the same
      record review. By adding a retrospective record review of randomly selected
      records to conventional incident-reporting, health care providers can gain a
      clearer and broader picture of commonly occurring, no-harm incidents in order to
      improve patient safety.

PMID- 23876024
TI  - Results of phase II levetiracetam trial following acute head injury in children
      at risk for posttraumatic epilepsy.
AB  - Posttraumatic seizures develop in up to 20% of children following severe
      traumatic brain injury (TBI). Children ages 6-17 years with one or more risk
      factors for the development of posttraumatic epilepsy, including presence of
      intracranial hemorrhage, depressed skull fracture, penetrating injury, or
      occurrence of posttraumatic seizure were recruited into this phase II study.
      Treatment subjects received levetiracetam 55 mg/kg/day, b.i.d., for 30 days,
      starting within 8 h postinjury. The recruitment goal was 20 treated patients.
      Twenty patients who presented within 8-24 h post-TBI and otherwise met
      eligibility criteria were recruited for observation. Follow-up was for 2 years.
      Forty-five patients screened within 8 h of head injury met eligibility criteria
      and 20 were recruited into the treatment arm. The most common risk factor present
      for pediatric inclusion following TBI was an immediate seizure. Medication
      compliance was 95%. No patients died; 19 of 20 treatment patients were retained
      and one observation patient was lost to follow-up. The most common severe adverse
      events in treatment subjects were headache, fatigue, drowsiness, and
      irritability. There was no higher incidence of infection, mood changes, or
      behavior problems among treatment subjects compared to observation subjects. Only
      1 (2.5%) of 40 subjects developed posttraumatic epilepsy (defined as seizures >7
      days after trauma). This study demonstrates the feasibility of a pediatric
      posttraumatic epilepsy prevention study in an at-risk traumatic brain injury
      population. Levetiracetam was safe and well tolerated in this population. This
      study sets the stage for implementation of a prospective study to prevent
      posttraumatic epilepsy in an at-risk population.

PMID- 23876025
TI  - An unusual case of glomerulonephritis in a patient with non-Hodgkin mucosal
      associated lymphoid tissue (MALT) B-cell lymphoma.
AB  - BACKGROUND: Kidney involvement in non-Hodgkin lymphoma is well recognized and
      glomerulonephritis, when present, has been commonly reported to be associated
      with a membranoproliferative pattern. CASE PRESENTATION: We report a case of a 58
      year-old lady with a recurrence of non-Hodgkin MALT B-cell lymphoma, presenting
      with acute kidney injury, nephrotic range proteinuria and a cellular urinalysis.
      She underwent a renal biopsy that showed a severe diffuse proliferative and
      exudative lupus-like glomerulonephritis, which is likely paraneoplastic in
      nature. We discuss the differential diagnosis and possible pathogenesis of
      glomerular injury in lymphoma-related proliferative glomerulonephritis.
      CONCLUSION: Differentiating between true lupus nephritis and a paraneoplastic
      glomerulonephritis is important, as it would have significant implications on
      treatment and clinical course.

PMID- 23876026
TI  - Conjugation of basic fibroblast growth factor on a heparin gradient for
      regulating the migration of different types of cells.
AB  - Regulation of cell migration by cell growth factors is critical in tissue
      regeneration such as angiogenesis, wound healing, and bone formation. In this
      work, basic fibroblast growth factor (bFGF) with a density varying between 0 and
      295 ng/cm2 was conjugated on heparinized glass slides. The amount of conjugated
      bFGF was determined by immunofluorescent staining. The mobility of vascular
      smooth muscle cells (VSMCs) was largely dominated by the bFGF density, whereas
      that of mesenchymal stem cells (MSCs) and endothelial cells (ECs) was slightly
      influenced. The migration rate of VSMCs increased initially and then decreased
      along with the increase of bFGF density. The fastest rate (22 MUm/h) was found on
      the bFGF surface with a density of 83 ng/cm2. The intrinsic mechanisms of the
      diverse migration behaviors of the VSMCs, MSCs, and ECs were revealed by studying
      the expression of bFGF receptors and migration-related proteins. The results show
      that the cell mobility is regulated by complex and synergetic intracellular
      signals in a cell type-dependent manner.

PMID- 23876027
TI  - Diagnostic significance of total creatine kinase and its isoform in tubal ectopic
      pregnancy.
AB  - AIM: Tubal ectopic pregnancy (tEP) must be diagnosed as early as possible because
      it is one of the leading causes of pregnancy-related death in the first
      trimester. The aim of this study was to evaluate the diagnostic value of serum
      total creatine kinase (CK) and its isoforms in diagnosis of tEP. METHODS: The
      study included 32 tEP cases, and gestational age-matched intrauterine (IU)
      abortion and normal pregnancy cases (n = 31 each). Serum total CK and CK-MB
      fraction were measured by the principle of spectrophotometry and CK-MM fraction
      was calculated from the above parameters. Serum beta-hCG was measured using
      chemiluminescent immunoassay. All study parameters were measured at the time of
      presentation. RESULTS: Serum beta-hCG levels were significantly low in patients
      with both tEP and IU abortion than normal pregnancy. Women with tEP had higher
      concentrations of total CK, CK-MM and lower concentrations of CK-MB% compared to
      both gestational age-matched IU pregnancy controls and IU abortion. Receiver
      operator characteristic analysis revealed that the optimal cut-off for total CK,
      CK-MM and CPK-MB% as predictors of ruptured EP were 147 IU/L, 135 IU/L and 10%,
      respectively, with the former two having higher specificity, and latter high
      sensitivity. CONCLUSION: Estimation of CK and its CK isoenzyme fractions can aid
      in quick and accurate diagnosis of tEP.

PMID- 23876028
TI  - Reactive oxygen species production by quercetin causes the death of Leishmania
      amazonensis intracellular amastigotes.
AB  - The present study reports the mechanism of the antileishmanial activity of
      quercetin against the intracellular amastigote form of Leishmania amazonensis.
      Treatment with 1 reduced the infection index in L. amazonensis-infected
      macrophages in a dose-dependent manner, with an IC50 value of 3.4 MUM and a
      selectivity index of 16.8, and additionally increased ROS generation also in a
      dose-dependent manner. Quercetin has been described as a pro-oxidant that induces
      the production of reactive oxygen species, which can cause cell death. Taken
      together, these results suggest that ROS production plays a role in the mechanism
      of action of 1 in the control of intracellular amastigotes of L. amazonensis.

PMID- 23876029
TI  - Isometric training with maximal co-contraction instruction does not increase co
      activation during exercises against external resistances.
AB  - The present investigation verified that strength is improved by a training
      programme consisting of repetitions of maximal isometric voluntary co
      contractions without increasing co-activations during contractions against
      external resistances. Ten participants performed 12 training sessions (four sets
      of 6 * 4 second maximal isometric co-contraction of the elbow flexor and
      extensors, 3 days a week for 4 weeks). Surface electromyograms of triceps and
      biceps brachii were collected during maximal voluntary isometric elbow flexion
      and extension against a force transducer. Maximal voluntary isometric force
      increased significantly after training, by 13.8 +/- 6.0% (extension) and 9.6 +/-
      9.5% (flexion), but the observed increases in EMG of agonist muscles during
      maximal voluntary contraction were not significant. No significant changes in the
      levels of co-activation of the elbow flexors and extensors were observed. No
      significant change was observed for all the parameters in a control group of ten
      participants. These results indicated that the strength improvements after co
      contraction training occur without increases in co-activation level.

PMID- 23876031
TI  - Single-step formation of ZnO/ZnWO(x) bilayer structure via interfacial
      engineering for high performance and low energy consumption resistive memory with
      controllable high resistance states.
AB  - A spontaneously formed ZnO/ZnWOx bilayer resistive memory via an interfacial
      engineering by one-step sputtering process with controllable high resistance
      states was demonstrated. The detailed formation mechanism and microstructure of
      the ZnWOx layer was explored by X-ray photoemission spectroscopy (XPS) and
      transmission electron microscope in detail. The reduced trapping depths from 0.46
      to 0.29 eV were found after formation of ZnWOx layer, resulting in an asymmetric
      I-V behavior. In particular, the reduction of compliance current significantly
      reduces the switching current to reach the stable operation of device, enabling
      less energy consumption. Furthermore, we demonstrated an excellent performance of
      the complementary resistive switching (CRS) based on the ZnO/ZnWOx bilayer
      structure with DC endurance >200 cycles for a possible application in three
      dimensional multilayer stacking. 

PMID- 23876030
TI  - Large-area free-standing ultrathin single-crystal silicon as processable
      materials.
AB  - Silicon has been driving the great success of semiconductor industry, and
      emerging forms of silicon have generated new opportunities in electronics,
      biotechnology, and energy applications. Here we demonstrate large-area free
      standing ultrathin single-crystalline Si at the wafer scale as new Si materials
      with processability. We fabricated them by KOH etching of the Si wafer and show
      their uniform thickness from 10 to sub-2 MUm. These ultrathin Si exhibits
      excellent mechanical flexibility and bendability more than those with 20-30 MUm
      thickness in previous study. Unexpectedly, these ultrathin Si materials can be
      cut with scissors like a piece of paper, and they are robust during various
      regular fabrication processings including tweezer handling, spin coating,
      patterning, doping, wet and dry etching, annealing, and metal deposition. We
      demonstrate the fabrication of planar and double-sided nanocone solar cells and
      highlight that the processability on both sides of surface together with the
      interesting property of these free-standing ultrathin Si materials opens up
      exciting opportunities to generate novel functional devices different from the
      existing approaches. 

PMID- 23876032
TI  - Effect of hCG and eCG treatments on prostaglandins synthesis in the porcine
      oviduct.
AB  - The oviduct plays a crucial role in fertilization, gamete maturation and embryo
      transport. Prostaglandins are some of the main factors determining its roles. The
      present study investigated the influence of oestrus synchronization and
      superovulation on prostaglandins synthesis in the porcine oviduct. Mature cross
      bred gilts after exhibiting oestrous cycles were divided into four groups: I,
      cyclic; II, inseminated; III, synchronized and inseminated; and IV, superovulated
      and inseminated. Oviducts were collected on the third day of the oestrous cycle
      or after insemination and divided into isthmus and ampullary parts. This study
      demonstrated lower mRNA (in the isthmus and ampulla; p < 0.05, p < 0.001,
      respectively) and protein prostaglandin endoperoxide synthase 2 expression (in
      the isthmus; p < 0.001) in gilts treated with human chorionic
      gonadotrophin/equine chorionic gonadotrophin (hCG/eCG) compared with Group II
      that were inseminated only. In addition, hCG and eCG treatment decreased mPGES-1
      mRNA levels in Groups III and IV, in both the isthmus (p < 0.01 in III, p < 0.001
      in IV) and ampulla (p < 0.001). The prostaglandin E2 content of oviductal tissues
      was significantly lower in Groups III (p < 0.05) and IV (p < 0.01 in isthmus, p <
      0.0001 in ampulla) compared with Group II. mRNA and protein levels of PGFS in
      Group IV in the oviductal isthmus were higher (p < 0.01) compared with the non
      treated Group II. In effect, the amount of prostaglandin F2alpha in oviductal
      tissues of gilts treated with hCG/eCG was significantly elevated (p < 0.001 in
      isthmus of Groups III and IV; p < 0.05 in ampulla of Group IV). Differential
      expression of the factors analysed in gilts treated with exogenous gonadotrophins
      suggests that hCG/eCG stimulation affects prostaglandins synthesis pathway. These
      changes can alter oviduct functions and in turn affect gamete maturation and
      fertilization as well as development of embryos and their transport to the
      uterus. 

PMID- 23876033
TI  - Nanoscale observations of magnesite growth in chloride- and sulfate-rich
      solutions.
AB  - Magnesite growth in chloride and sulfate-rich solutions has been examined at 90 
      degrees C in situ using phase-shift interferometry (PSI) and ex situ using atomic
      force microscopy (AFM) to evaluate the feasibility of cosequestering SO2 and CO2
      in Mg-rich rocks. Although sulfate may assist desolvation at the magnesite
      surface, evidence for enhanced growth was only found at specific surface sites.
      The overall growth rates fit with those observed for chloride experiments in
      similarly saturated solutions. Thus, the formation of Mg-SO4 ion pairs in
      solution, which lowers the supersaturation with respect to magnesite, will have
      the dominant effect during sequestration. Lowering the activity of Mg(2+) ions in
      solution also inhibited the nucleation of other hydrated Mg-carbonate phases. As
      no evidence was found for sulfate incorporation into the growing magnesite, the
      presence of sulfate in solution will be detrimental to CO2 sequestration and is
      not expected to be cosequestered. The PSI data also emphasize the variability of
      reactivity over the surface and how this changes as a function of solution
      saturation and composition. 

PMID- 23876034
TI  - Glycemic variability in relation to oral disposition index in the subjects with
      different stages of glucose tolerance.
AB  - BACKGROUND: Glucose variability could be an independent risk factor for diabetes
      complications in addition to average glucose. The deficiency in islet beta cell
      secretion and insulin sensitivity, the two important pathophysiological
      mechanisms of diabetes, are responsible for glycemic disorders. The oral
      disposition index evaluated by product of insulin secretion and sensitivity is a
      useful marker of islet beta cell function. The aim of the study is to investigate
      glycemic variability in relation to oral disposition index in the subjects across
      a range of glucose tolerance from the normal to overt type 2 diabetes. METHODS:
      75-g oral glucose tolerance test (OGTT) was performed in total 220 subjects: 47
      with normal glucose regulation (NGR), 52 with impaired glucose metabolism (IGM, 8
      with isolated impaired fasting glucose [IFG], 18 with isolated impaired glucose
      tolerance [IGT] and 26 with combined IFG and IGT), 61 screen-diagnosed diabetes
      by isolated 2-h glucose (DM2h) and 60 newly diagnosed diabetes by both fasting
      and 2-h glucose (DM). Insulin sensitivity index (Matsuda index, ISI), insulin
      secretion index (DeltaI30/DeltaG30), and integrated beta cell function measured
      by the oral disposition index (DeltaI30/DeltaG30 multiplied by the ISI) were
      derived from OGTT. All subjects were monitored using the continuous glucose
      monitoring system for consecutive 72 hours. The multiple parameters of glycemic
      variability included the standard deviation of blood glucose (SD), mean of blood
      glucose (MBG), high blood glucose index (HBGI), continuous overlapping net
      glycemic action calculated every 1 h (CONGA1), mean of daily differences (MODD)
      and mean amplitude of glycemic excursions (MAGE). RESULTS: From the NGR to IGM to
      DM2h to DM group, the respective values of SD (mean +/- SD) (0.9 +/- 0.3, 1.5 +/-
      0.5, 1.9 +/- 0.6 and 2.2 +/- 0.6 mmol/), MBG (5.9 +/- 0.5, 6.7 +/- 0.7, 7.7 +/-
      1.0 and 8.7 +/- 1.5 mmol/L), HGBI [median(Q1-Q3)][0.8(0.2-1.2), 2.0(1.2-3.7),
      3.8(2.4-5.6) and 6.4(3.2-9.5)], CONGA1 (1.0 +/- 0.2, 1.3 +/- 0.2, 1.5 +/- 0.3 and
      1.8 +/- 0.4 mmol/L), MODD (0.9 +/- 0.3, 1.4 +/- 0.4, 1.8 +/- 0.7 and 2.1 +/- 0.7
      mmol/L) and MAGE (2.1 +/- 0.6, 3.3 +/- 1.0, 4.3 +/- 1.4 and 4.8 +/- 1.6 mmol/L)
      were all increased progressively (all p < 0.05), while their oral disposition
      indices [745(546-947), 362(271-475), 203(134-274) and 91(70-139)] were decreased
      progressively (p < 0.05). In addition, SD, MBG, HGBI, CONGA1, MODD and MAGE were
      all negatively associated with the oral disposition index in each group (all p <
      0.05) and in the entire data set (r = -0.66, -0.66, -0.72, -0.59, -0.61 and 
      0.65, respectively, p < 0.05). CONCLUSIONS: Increased glycemic variability
      parameters are consistently associated with decreased oral disposition index in
      subjects across the range of glucose tolerance from the NGR to IGM to DM2h to DM
      group.

PMID- 23876035
TI  - Water slug formation and motion in gas flow channels: the effects of geometry,
      surface wettability, and gravity.
AB  - Water emerging from ~100 MUm pores into millimeter-size gas flow channels forms
      drops that grow and become slugs which span the flow channel. Flowing gas causes
      the slugs to detach and move down the channel. The effect of channel geometry,
      surface wettability, and gravity on the formation and motion of water slugs has
      been analyzed using high-speed video images of the drops and differential
      pressure-time traces. Drops grow and appear, assuming a sequence of shapes that
      minimize the total interfacial energy of the gas-liquid and liquid-solid
      interfaces. The drops are initially spherical caps centered on the pore (the
      liquid contacts one wall). Above a certain size, the drops move to the corner,
      forming "corner drops" (the liquid contacts two walls). Corner drops grow across
      the channel, evolving into partial liquid bridges (drops confined by three
      walls), and finally the drops span the channel cross-section forming slugs
      (contacting all four walls). Smaller slugs are formed in channels with
      hydrophobic walls than in channels with hydrophilic walls. Smaller slugs are
      formed in channels with curved walls than in square or rectangular channels.
      Slugs move when the differential gas pressure overcomes the force to move the
      advancing and receding gas-liquid-solid contact lines of the slugs. Residual
      water left behind in corners by moving slugs reduces the barriers for drops to
      form slugs, causing the steady-state slug volumes to be smaller than those seen
      at start-up in dry channels. 

PMID- 23876036
TI  - Investigational anticoagulants for hematological conditions: a new generation of
      therapies.
AB  - INTRODUCTION: The introduction of novel anticoagulants has had contrasting
      effects on the agents in the pipeline, fueling the development of some and
      sinking the others. The complexity of the coagulation cascade offers interesting
      inhibition choices that might become valid treatment options. AREAS COVERED: This
      review will highlight some of the anticoagulants in the pipeline. Following the
      success of the direct thrombin and FXa inhibitors already in the market, new
      agents are being tested. These include AZD0837, betrixaban, letaxaban, darexaban,
      and LY517717. Targeting other components of the hemostatic pathway might lead to
      better safety profiles without influencing efficacy. Inhibitors to FVIIa-tissue
      factor (FVIIa/TF) complex, FIX, FXI, and FXII are being assessed. New inspiring
      inhibitors are antisense oligonucleotides (ASOs) and aptamers. These are highly
      specific agents with readily reversible effect and might be engineered to inhibit
      any coagulation factor. Currently tested ASOs and aptamers are inhibitors of FXI,
      FXII, thrombin, FIXa, and platelet GPIV. EXPERT OPINION: Some of the agents in
      the pipeline offer valid treatment option for long-term therapy, overcoming some
      of the drawbacks of the novel anticoagulants. Research is being driven by an
      expanding market in the anticoagulation field that has been unexploited for a
      long time.

PMID- 23876037
TI  - West Nile virus methyltransferase domain interacts with protein kinase G.
AB  - BACKGROUND: The flaviviral nonstructural protein 5 (NS5) is a phosphoprotein,
      though the precise identities and roles of many specific phosphorylations remain
      unknown. Protein kinase G (PKG), a cGMP-dependent protein kinase, has previously
      been shown to phosphorylate dengue virus NS5. METHODS: We used mass spectrometry
      to specifically identify NS5 phosphosites. Co-immunoprecipitation assays were
      used to study protein-protein interactions. Effects on viral replication were
      measured via replicon system and plaque assay titering. RESULTS: We identified
      multiple sites in West Nile virus (WNV) NS5 that are phosphorylated during a WNV
      infection, and showed that the N-terminal methyltransferase domain of WNV NS5 can
      be specifically phosphorylated by PKG in vitro. Expressing PKG in cell culture
      led to an enhancement of WNV viral production. We hypothesized this effect on
      replication could be caused by factors beyond the specific phosphorylations of
      NS5. Here we show for the first time that PKG is also able to stably interact
      with a viral substrate, WNV NS5, in cell culture and in vitro. While the mosquito
      borne WNV NS5 interacted with PKG, tick-borne Langat virus NS5 did not. The
      methyltransferase domain of NS5 is able to mediate the interaction between NS5
      and PKG, and mutating positive residues in the alphaE region of the
      methyltransferase interrupts the interaction. These same mutations completely
      inhibited WNV replication. CONCLUSIONS: PKG is not required for WNV replication,
      but does make a stable interaction with NS5. While the consequence of the NS5:PKG
      interaction when it occurs is unclear, mutational data demonstrates that this
      interaction occurs in a region of NS5 that is otherwise necessary for
      replication. Overall, the results identify an interaction between virus and a
      cellular kinase and suggest a role for a host kinase in enhancing flaviviral
      replication.

PMID- 23876038
TI  - Sex differences in depressive, anxious behaviors and hippocampal transcript
      levels in a genetic rat model.
AB  - Major depressive disorder (MDD) is a common, debilitating illness with high
      prevalence of comorbid anxiety. The incidence of depression and of comorbid
      anxiety is much higher in women than in men. These gender biases appear after
      puberty and their etiology is mostly unknown. Selective breeding of the Wistar
      Kyoto (WKY) rat strain, an accepted model of adult and adolescent depression,
      resulted in two fully inbred substrains. Adult WKY more immobile (WMI) rats of
      both sexes consistently show increased depression-like behavior in the forced
      swim test when compared with the control WKY less immobile (WLI) strain. In
      contrast, here we show that while adult female WMIs and WLIs both display high
      anxiety-like behaviors, only WLI males, but not WMI males, show this behavior.
      Moreover, the behavioral profile of WMI males is consistent from early
      adolescence to adulthood, but the high depression- and anxiety-like behaviors of
      the female WMIs appear only in adulthood. These sex-specific behavioral patterns
      are paralleled by marked sex differences in hippocampal gene expression
      differences established by genome-wide transcriptional analyses of 13th
      generation WMIs and WLIs. Moreover, sex- and age-specific differences in
      transcript levels of selected genes are present in the hippocampus of the
      current, fully inbred WMIs and WLIs. Thus, the contribution of specific genes
      and/or the influence of the gonadal hormonal environment to depression- and
      anxiety-like behaviors may differ between male and female WMIs, resulting in
      their distinct behavioral and transcriptomic profiles despite shared sequences of
      the somatic chromosomes. 

PMID- 23876040
TI  - Ushering in an era of community-based palliative care.

PMID- 23876041
TI  - Structure and reactivity of distanna[2]metallocenophanes of ruthenium and osmium.
AB  - We report the molecular structures of 1,1'-dilithiometallocenes of ruthenium and
      osmium. These compounds served as precursors for the synthesis and subsequent
      structural characterization of the first [2]osmocenophanes with disilane and
      distannane bridges, as well as of a distanna[2]ruthenocenophane. In addition, the
      insertion of sulfur and selenium into the Sn-Sn bridges was studied and it was
      observed that the presence of the Lewis base pmdta (N,N,N',N",N"
      pentamethyldiethylenetriamine) dramatically accelerates the reaction. 

PMID- 23876042
TI  - Cardiac responses to 24 hrs hyperoxia in Bmp2 and Bmp4 heterozygous mice.
AB  - BACKGROUND: Hyperoxia or clinical oxygen (O2) therapy is known to result in
      increased oxidative burden. Therefore, understanding susceptibility to hyperoxia
      exposure is clinically important. Bone morphogenetic proteins (BMPs) 2 and 4 are
      involved in cardiac development and may influence responses to hyperoxia.
      METHODS: Bmp2(+/)(-). Bmp4(+/)(-) and wild-type mice were exposed to hyperoxia
      (100% O2) for 24 hrs. Electrocardiograms (ECG) were recorded before and during
      exposure by radio-telemetry. RESULTS: At baseline, a significantly higher low
      frequency (LF) and total power (TP) heart rate variability (HRV) were found in
      Bmp2(+/)(-) mice only (p < 0.05). Twenty-four hours hyperoxia-induced strain
      independent reductions in heart rate, QTcB and ST-interval and increases in QRS,
      LF HRV and standard deviation of RR-intervals were observed. In Bmp4(+/)(-) mice
      only, increased PR-interval (PR-I) (24 hrs), P-wave duration (P-d; 18 and 21-24
      hrs), PR-I minus P-d (PR - Pd; 24 hrs) and root of the mean squared differences
      of successive RR-intervals (24 hrs) were found during hyperoxia (p < 0.05).
      DISCUSSION: Elevated baseline LF and TP HRV in Bmp2(+/)(-) mice suggests an
      altered autonomic nervous system regulation of cardiac function in these mice.
      However, this was not related to strain specific differences in responses to 24
      hrs hyperoxia. During hyperoxia, Bmp4(+/-) mice were the most susceptible in
      terms of atrioventricular conduction changes and risk of atrial fibrillation,
      which may have important implications for patients treated with O2 who also
      harbor Bmp4 mutations. This study demonstrates significant ECG and HRV responses
      to 24 hrs hyperoxia in mice, which highlights the need to further work on the
      genetic mechanisms associated with cardiac susceptibility to hyperoxia.

PMID- 23876044
TI  - Vibrational sum frequency generation spectroscopy of secondary organic material
      produced by condensational growth from alpha-pinene ozonolysis.
AB  - Secondary organic material (SOM) was produced in a flow tube from alpha-pinene
      ozonolysis, and collected particles were analyzed spectroscopically via a
      nonlinear coherent vibrational spectroscopic technique, namely sum frequency
      generation (SFG). The SOM precursor alpha-pinene was injected into the flow tube
      reactor at concentrations ranging from 0.125 +/- 0.01 ppm to 100 +/- 3 ppm. The
      oxidant ozone was varied from 0.15 +/- 0.02 to 194 +/- 2 ppm. The residence time
      was 38 +/- 1 s. The integrated particle number concentrations, studied using a
      scanning mobility particle sizer (SMPS), varied from no particles produced up to
      (1.26 +/- 0.02) * 10(7) cm(-3) for the matrix of reaction conditions. The mode
      diameters of the aerosols increased from 7.7 nm (geometric standard deviation
      (gsd), 1.0) all the way to 333.8 nm (gsd, 1.9). The corresponding volume
      concentrations were as high as (3.0 +/- 0.1) * 10(14) nm(3) cm(-3). The size
      distributions indicated access to different particle growth stages, namely
      condensation, coagulation, or combination of both, depending on reaction
      conditions. For filter collection and subsequent spectral analysis, reaction
      conditions were selected that gave a mode diameter of 63 +/- 3 nm and 93 +/- 3
      nm, respectively, and an associated mass concentration of 12 +/- 2 MUg m(-3) and
      (1.2 +/- 0.1) * 10(3) MUg m(-3) for an assumed density of 1200 kg m(-3). Teflon
      filters loaded with 24 ng to 20 MUg of SOM were analyzed by SFG. The SFG spectra
      obtained from particles formed under condensational and coagulative growth
      conditions were found to be quite similar, indicating that the distribution of
      SFG-active C-H oscillators is similar for particles prepared under both
      conditions. The spectral features of these flow-tube particles agreed with those
      prepared in an earlier study that employed the Harvard Environmental Chamber. The
      SFG intensity was found to increase linearly with the number of particles,
      consistent with what is expected from SFG signal production from particles, while
      it decreased at higher mass loadings of 10 and 20 MUg, consistent with the notion
      that SFG probes the top surface of the SOM material following the complete
      coverage of the filter. The linear increase in SFG intensity with particle
      density also supports the notion that the average number of SFG active
      oscillators per particle is constant for a given particle size, that the
      particles are present on the collection filters in a random array, and that the
      particles are not coalesced. The limit of detection of SFG intensity was
      established as 24 ng of mass on the filter, corresponding to a calculated density
      of about 100 particles in the laser spot. As established herein, the technique is
      applicable for detecting low particle number or mass concentrations in ambient
      air. The related implication is that SFG is useful for short collection times and
      would therefore provide increased temporal resolution in a locally evolving
      atmospheric environment. 

PMID- 23876043
TI  - New paradigms for treatment-resistant depression.
AB  - Clinical depression is a serious mental disorder characterized by low mood,
      anhedonia, loss of interest in daily activities, and other symptoms, and is
      associated with severe consequences including suicide and increased risk of
      cardiovascular events. Depression affects nearly 15% of the population. The
      standard of care for the last 50 years has focused on monoamine
      neurotransmitters, including such treatments as selective serotonin reuptake
      inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
      However, these treatments have significant limitations: they can take weeks
      before showing mood-altering effects, and only one to two out of ten patients
      shows clinical effects beyond those associated with placebo. A major paradigm
      shift in research into the treatment of depression is underway, based on
      promising results with the glutamatergic NMDA receptor antagonist ketamine.
      Further research has demonstrated the significance of glutamatergic pathways in
      depression and the association of this system with the stress pathway and
      magnesium homeostasis. Treatment with NMDA receptor antagonists and magnesium
      have shown the ability to sprout new synaptic connections and reverse stress
      induced neural changes, opening up promising new territory for the development of
      drugs to meet the unmet need in patients with clinical depression. 

PMID- 23876045
TI  - Anti-inflammatory strategies to reduce acute kidney injury in cardiac surgery
      patients: a meta-analysis of randomized controlled trials.
AB  - Acute kidney injury (AKI) after cardiac operations is a serious complication
      associated with postoperative mortality. Multiple factors contribute to AKI
      development, principally ischemia-reperfusion injury and inflammatory response.
      It is well proven that glucocorticoid administration, leukocyte filter
      application, and miniaturized extracorporeal circuits (MECC) modulate
      inflammatory response. We conducted a systematic review of randomized controlled
      trials (RCTs) in which one of these inflammatory system modulation strategies was
      used, with the aim to evaluate the effects on postoperative AKI. MEDLINE and
      Cochrane Library were screened through November 2011 for RCTs in which an
      inflammatory system modulation strategy was adopted. Included were trials that
      reported data about postoperative renal outcomes. Because AKI was defined by
      different criteria, including biochemical determinations, urine output, or
      dialysis requirement, we unified renal outcome as worsening renal function (WRF).
      We identified 14 trials for steroids administration (931 patients, WRF incidence
      [treatment vs. placebo]: 2.7% vs. 2.4%; OR: 1.13; 95% CI: 0.53-2.43; P = 0.79), 9
      trials for MECC (947 patients, WRF incidence: 2.4% vs. 0.9%; OR: 0.47; 95% CI:
      0.18-1.25; P = 0.13), 6 trials for leukocyte filters (374 patients, WRF
      incidence: 1.1% vs. 7.5%; OR: 0.18; 95% CI: 0.05-0.64; P = 0.008). Only leukocyte
      filters effectively reduced WRF incidence. Not all cardiopulmonary bypass-related
      anti-inflammatory strategies analyzed reduced renal damage after cardiac
      operations. In adult patients, probably other factors are predominant on
      inflammation in determining AKI, and only leukocyte filters were effective. Large
      multicenter RCTs are needed in order to better evaluate the role of inflammation
      in AKI development after cardiac operations. 

PMID- 23876046
TI  - The world is flat?

PMID- 23876048
TI  - Periodic nanowire array at the crystal interface.
AB  - A dislocation in a crystalline material has dangling bonds at its core and a
      strong strain field in its vicinity. Consequently, the dislocation attracts
      solute atoms and forms a so-called Cottrell atmosphere along the dislocation. A
      crystalline dislocation can be used as a template to produce nanowires by
      selectively doping foreign atoms along the dislocation. However, control of the
      configuration, spacing, and density of the formed periodic nanowire array has
      heretofore been extremely difficult. Here we show a method for fabricating
      ordered, electrically conductive nanowire arrays using periodic dislocations at
      crystal interfaces. As a demonstration, we fabricated arrays of titanium
      nanowires arranged at intervals of either 13 or 90 nm and then confirmed by
      scanning probe microscopy that they exhibit electrical conductivity inside an
      insulating aluminum oxide. Significantly, we were able to precisely control
      nanowire periodicity by the choice of crystal orientation and/or crystal planes
      at the crystal interface. This simple method for the fabrication of periodic
      nanowire arrays of highly controlled density should be widely applicable to
      electrical, magnetic, and optical devices. 

PMID- 23876049
TI  - Anterior scleritis and celiac disease: a proposed association.

PMID- 23876051
TI  - Invitation withdrawn: humanitarian action, United Nations peacekeeping, and state
      sovereignty in Chad.
AB  - This paper looks at the three-way relationship between the Government of Chad,
      humanitarians, and the United Nations Mission in the Central African Republic and
      Chad (MINURCAT) from 2004 until June 2011. Chad was never comfortable with the
      international presence of either humanitarians or peacekeepers and asserted its
      sovereignty increasingly during this period. MINURCAT was deployed in 2008 to
      protect humanitarian workers and to facilitate the provision of humanitarian
      assistance in eastern Chad. This association between the UN mission and
      humanitarian agencies contributed to making the latter the target of repressive
      practices by the government, such as the imposition of armed escorts. Facing a
      steep learning curve, Chad and its state officials gradually appropriated the
      discourse of the humanitarian and international community and ultimately, in
      2010, requested the departure of MINURCAT, claiming that they could meet the
      protection needs of vulnerable populations in eastern Chad on their own. 

PMID- 23876050
TI  - Small molecule inhibitors of multidrug resistance gene (MDR1) expression:
      preclinical evaluation and mechanisms of action.
AB  - The resistance of tumors to a number of structurally and functionally unrelated
      chemotherapeutic drugs has been a major obstacle for successful cancer
      chemotherapy. An important mechanism leading to multidrug resistance (MDR) is the
      overexpression of the 170 kDa P-glycoprotein (P-gp), which is a member of the ATP
      binding cassette (ABC) superfamily of membrane transporters, encoded by the MDR1
      gene. Aiming to overcome MDR and due to the clinical failure of P-gp inhibitors,
      downregulation of MDR1 expression by small molecules has been studied as a
      possible cancer adjuvant chemotherapy. Here we review the current knowledge on
      MDR1 gene expression downregulation by small molecules and the mechanisms
      underlying those effects observed in cancer cell lines, in an attempt to identify
      targets for future therapeutic interventions. 

PMID- 23876052
TI  - Pre-exposure prophylaxis for conception (PrEP-C) as a risk reduction strategy in
      HIV-positive men and HIV-negative women in the UK.
AB  - Couples wishing to have biological children when one partner is HIV positive and
      the other is HIV negative present clinicians with complex clinical, social and
      ethical considerations. We established two multidisciplinary pre-conception
      services for HIV-positive individuals and their partners. We report the first UK
      use of pre-exposure prophylaxis for conception (PrEP-C) as part of an overall
      risk reduction strategy. Couples were counselled and written informed consent for
      PrEP-C was obtained. Patient demographics, HIV and medical histories were
      recorded. Males underwent baseline semen analysis and seminal HIV viral load
      testing. Females had full fertility screens. Both partners were screened for
      sexually transmitted infections. All couples used timed ovulatory intercourse
      (TOI). Tenofovir+/-emtricitabine was taken by the female at protocol designated
      times before+/-after TOI. Thirty-two male positive/female negative couples used
      the services. Thirteen couples have used PrEP-C (median age of male 41 years
      (range 32-56), female 31 (28-43); median CD4 533 (236-1194); all male plasma and
      seminal HIV viral loads were undetectable). Eleven pregnancies in 10 couples have
      resulted in 7 live births, 1 ongoing pregnancy and 4 miscarriages (5/40, 6/40,
      10/40 and 1 twin 17/40) after a median of 2.5 attempts (range 1-5). PrEP-C was
      well tolerated with no discontinuations and no HIV transmissions. These data
      suggest that PrEP-C is a safe and effective option for serodiscordant couples
      wishing to conceive; a standardised protocol has been developed; data collection
      via a central database is under way.

PMID- 23876053
TI  - Glomerular filtration rate (GFR) determination via individual kinetics of the
      inulin-like polyfructosan sinistrin versus creatinine-based population-derived
      regression formulae.
AB  - BACKGROUND: In renal patients estimation of GFR is routinely done by means of
      population-based formulae using serum creatinine levels. For GFR determination in
      the creatinine-blind regions or in cases of reno-hepatic syndrome as well as in
      critical cases of live kidney donors individualized measurements of GFR (mGFR)
      employing the kinetics of exogenous filtration markers such as the inulin-like
      polyfructosan sinistrin are necessary. The goal of this study is to compare mGFR
      values with the eGFR values gained by the Modification of Diet in Renal Disease
      (MDRD4) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulae.
      METHODS: In 170 subjects comprising persons with normal renal function or with
      various stages of kidney diseases (CKD 1-4) GFR was measured by application of
      intravenous bolus of sinistrin and assessment of temporal plasma concentration
      profiles by means of pharmacokinetic methods (mGFR). Comparisons of mGFR with
      MDRD4- and CKD-EPI-derived eGFR values were performed by means of linear
      regression and Bland-Altman analyses. RESULTS: Reasonable agreement of mGFR and
      eGFR values was observed in patients with poor renal function [GFR below 60
      (ml/min)/1.73 m2]. In cases of normal or mildly impaired renal function, GFR
      determination by MDRD4 or CKD-EPI tends to underestimate GFR. Notably, there is
      practically no difference between the two eGFR methods. CONCLUSIONS: For routine
      purposes or for epidemiological studies in cases of poor renal function eGFR
      methods are generally reliable. But in creatinine-blind ranges [GFR above 60
      (ml/min)/1.73 m2] eGFR values are unreliable and should be replaced by clinically
      and physiologically suitable methods for mGFR determination. CONSORT:
      http://www.consort-statement.org/index.aspx?o=1190.

PMID- 23876054
TI  - The transmission potential of Rift Valley fever virus among livestock in the
      Netherlands: a modelling study.
AB  - Rift Valley fever virus (RVFV) is a zoonotic vector-borne infection and causes a
      potentially severe disease. Many mammals are susceptible to infection including
      important livestock species. Although currently confined to Africa and the near
      East, this disease causes concern in countries in temperate climates where both
      hosts and potential vectors are present, such as the Netherlands. Currently, an
      assessment of the probability of an outbreak occurring in this country is
      missing. To evaluate the transmission potential of RVFV, a mathematical model was
      developed and used to determine the initial growth and the Floquet ratio, which
      are indicators of the probability of an outbreak and of persistence in a periodic
      changing environment caused by seasonality. We show that several areas of the
      Netherlands have a high transmission potential and risk of persistence of the
      infection. Counter-intuitively, these are the sparsely populated livestock areas,
      due to the high vector-host ratios in these areas. Culex pipiens s.l. is found to
      be the main driver of the spread and persistence, because it is by far the most
      abundant mosquito. Our investigation underscores the importance to determine the
      vector competence of this mosquito species for RVFV and its host preference.

PMID- 23876055
TI  - Physiological responses and performance in a simulated trampoline gymnastics
      competition in elite male gymnasts.
AB  - Physiological responses and performance were examined during and after a
      simulated trampoline competition (STC). Fifteen elite trampoline gymnasts
      participated, of which eight completed two routines (EX1 and EX2) and a
      competition final (EX3). Trampoline-specific activities were quantified by video
      analysis. Countermovement jump (CMJ) and 20 maximal trampoline jump (20-MTJ)
      performances were assessed. Heart rate (HR) and quadriceps muscle temperature
      (Tm) were recorded and venous blood was drawn. A total of 252 +/- 16 jumps were
      performed during the STC. CMJ performance declined (P < 0.05) by 3.8, 5.2 and
      4.2% after EX1, EX2 and EX3, respectively, and was 4.8% lower (P < 0.05) than
      baseline 24 h post-competition. 20-MTJ flight time was ~1% shorter (P < 0.05) for
      jump 1-10 after EX2 and 24 h post STC. Tm increased (P < 0.05) to ~39 degrees C
      after the warm-up, but declined (P < 0.05) 1.0 and 0.6oC before EX2 and EX3,
      respectively. Peak HR was 95-97% HRmax during EX1-3. Peak blood lactate, plasma
      K(+) and NH3 were 6.5 +/- 0.5, 6.0 +/- 0.2 mmol . l(-1) and 92 +/- 10 umol . l(
      1), respectively. Plasma CK increased (P < 0.05) by ~50 and 65% 0 and 24 h after
      STC. In conclusion, a trampoline gymnastic competition includes a high number of
      repeated explosive and energy demanding jumps, which impairs jump performance
      during and 24 h post-competition.

PMID- 23876057
TI  - Molecular mechanism of poor embryo development in postovulatory aged oocytes:
      mini review.
AB  - Oocyte quality is a key factor in determining embryo development; however, we
      have a poor understanding of what constitutes oocyte quality or the mechanisms
      governing it. Postovulatory aging of oocytes that have not been fertilized for a
      prolonged time after ovulation is known to significantly impair oocyte quality
      and subsequent embryo development after fertilization. Embryos derived from
      postovulatory-aged oocytes are prone to undergo apoptosis due to the decreased
      Bcl-2 expression. Postovulatory aging of oocytes changes the patterns of Ca(2+)
      oscillations at fertilization as a result of impaired Ca(2+) regulation in the
      endoplasmic reticulum. Moreover, postovulatory aging of oocytes impairs
      mitochondrial adenosine triphosphate production as a result of increasing
      oxidative stresses. Oxidative stresses also affect intracellular Ca(2+)
      regulation and impair embryo development after fertilization. Collectively, the
      mechanism of postovulatory oocyte aging might be involved in reactive oxygen
      species-induced mitochondrial injury followed by abnormal intracellular Ca(2+)
      regulation in the endoplasmic reticulum. 

PMID- 23876058
TI  - First evidence of manganese-nickel segregation and densification upon cycling in
      Li-rich layered oxides for lithium batteries.
AB  - Lithium-rich manganese-based layered oxides Li[Li(x)Mn(y)TM(1-x-y)]O2 with TM
      standing for Ni, Co, or Fe are of great interest as cathode materials for lithium
      ion batteries. Indeed, among all of the materials, they offer the highest
      rechargeable capacity and energy density. However, when used, they suffer from
      complex evolutions that need to be understood before their practical use. Here we
      report on such evolutions studied using advanced transmission electron
      microscopy. Structural modifications are directly observed at the atomic scale
      using Cs corrected STEM HAADF imaging technique, and the chemical modifications
      are probed by the means of STEM EELS experiments. For the first time, segregation
      between nickel and manganese close the particle surface is pointed out. Finally,
      observed evolutions are correlated within a proposed mechanism that leads to the
      densification of the material. Our results allow understanding the link between
      the decrease of electrochemical performance and these evolutions occurring into
      the material upon cycling.

PMID- 23876059
TI  - Nanoscale phase separation in DSPC-cholesterol systems.
AB  - The lipid arrangement of eukaryotic cell membranes has been shown to be
      heterogeneous, with domains enriched in cholesterol and saturated phospholipids,
      coexisting with a continuous phase that is enriched in unsaturated phospholipids.
      While the existence of these domains is well-established, there is still a lack
      of consensus regarding domain size and the factors influencing it. In this work,
      we investigate model membranes consisting of 1,2-dioleoyl-sn-glycero-3
      phosphocholine (DOPC)-1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
      cholesterol (Chol) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC,
      18:1-16:0)-DSPC-Chol with a steady-state fluorescence assay and report the
      influence of phospholipid chain saturation and chain length on domain size. The
      spectral shifts of 1-myristoyl-2-[12-[(5-dimethylamino-1
      naphthalenesulfonyl)amino]dodecanoyl]-sn-glycero-3-phosphocholine (DAN-PC) and a
      Forster resonance energy transfer (FRET) assay were used, along with an
      analytical model, to estimate domain sizes. A region of nanoscale domain
      existence was observed in both ternary systems; however, the domains formed in
      the system containing the asymmetric lipid (POPC, 18:1-16:0) were larger than
      those formed in the diunsaturated lipid (DOPC, 18:1-18:1). This is a new finding,
      as domains were not previously known to exist in similar POPC-based systems. 

PMID- 23876056
TI  - Role of commensal and probiotic bacteria in human health: a focus on inflammatory
      bowel disease.
AB  - The human gut is one of the most complex ecosystems, composed of 1013-1014
      microorganisms which play an important role in human health. In addition, some
      food products contain live bacteria which transit through our gastrointestinal
      tract and could exert beneficial effects on our health (known as probiotic
      effect). Among the numerous proposed health benefits attributed to commensal and
      probiotic bacteria, their capacity to interact with the host immune system is now
      well demonstrated. Currently, the use of recombinant lactic acid bacteria to
      deliver compounds of health interest is gaining importance as an extension of the
      probiotic concept. This review summarizes some of the recent findings and
      perspectives in the study of the crosstalk of both commensal and probiotic
      bacteria with the human host as well as the latest studies in recombinant
      commensal and probiotic bacteria. Our aim is to highlight the potential roles of
      recombinant bacteria in this ecosystem. 

PMID- 23876060
TI  - Novel pathogenic epitopes of myelin oligodendrocyte glycoprotein induce
      experimental autoimmune encephalomyelitis in C57BL/6 mice.
AB  - Myelin oligodendrocyte glycoprotein (MOG), a minor protein of the central nervous
      system myelin, is recognized as a potential target in multiple sclerosis and
      neuromyelitis optica. The extracellular domain of MOG is commonly used in a wide
      range of mouse strains and other animals to induce experimental autoimmune
      encephalomyelitis (EAE), an autoimmune animal model of multiple sclerosis,
      because it is a target for antibody-mediated attack. Previous studies, using
      selected peptides, have indicated that MOG(35-55) peptide is an encephalitogenic
      epitope in C57BL/6 (H-2(b)) mice. A more systematic analysis of both T-cell and B
      cell responses following immunization of C57BL/6 mice with either recombinant
      extracellular mouse MOG protein (1-116) or with overlapping peptides spanning the
      whole sequence of MOG, before assessment of responses to 15 mer and 23 mer
      peptides was undertaken. The studies identified T-cell responses within the
      MOG(35-55) (extracellular domain) but also two new immunogenic and
      encephalitogenic T-cell epitopes within residues MOG(113-127), MOG(120-134)
      (localized in the transmembrane region) and MOG(183-197) (in the second
      hydrophobic MOG domain). In addition, residue MOG(113-127) was found to be a B
      cell epitope, suggesting that this may be a useful adjunct for the induction of
      EAE as well as for immunological studies in C57BL/6 mice, which are increasingly
      being used to study immune function through the use of transgenic and gene
      knockout technology.

PMID- 23876061
TI  - Rapid oestrogenic regulation of social and nonsocial learning.
AB  - Much research on oestrogens has focused on their long-term action, exerting
      behavioural effects within hours to days through gene transcription. Oestrogens
      also affect behaviour on a much shorter time scale. These rapid effects are
      assumed to occur through cell signalling and can elicit a behavioural effect as
      early as 15 min after treatment. These effects on behaviour have primarily been
      explored through the action of oestradiol at three well-known oestrogen receptors
      (ERs): ERalpha, ERbeta and the more recently described G protein-coupled ER1
      (GPER1). The rapid effects of oestradiol and ER agonists have been tested on both
      social and nonsocial learning paradigms. Social learning refers to a paradigm in
      which an animal acquires information and modifies its behaviour based on
      observation of another animal, commonly studied using the social transmission of
      food preferences paradigm. When administered shortly before testing, oestradiol
      rapidly improves social learning on this task, although no ER agonist has
      definitive, comparable improving effects. Some evidence points to GPER1, whereas
      ERalpha impairs, and ERbeta activation has no effect on social learning.
      Conversely, ERalpha and GPER1 play a larger role than ERbeta in the rapid
      improving effect of oestrogens on nonsocial learning, including social and object
      recognition. In addition, when administered immediately post-acquisition,
      oestrogens also rapidly improve memory consolidation in a variety of learning
      paradigms: object recognition, object placement, inhibitory avoidance and the
      Morris water maze, indicating that oestradiol affects the consolidation of
      multiple types of memory. Evidence suggests that these improvements are the
      result of oestrogens acting in the dorsal hippocampus where selective activation
      of all three ERs shows rapid improving effects on spatial learning comparable to
      oestradiol. However, the hippocampus is not necessary for rapid oestradiol
      improvements on social recognition. Although acute treatment with oestradiol
      enhances learning and memory on various social and nonsocial learning paradigms,
      the specific ERs play different roles in each type of learning. Future research
      should aim to further determine the roles of ERs with respect to the enhancing
      effects of oestradiol on learning and memory, and also determine where in the
      brain oestradiol acts to affect social and nonsocial learning. 

PMID- 23876063
TI  - Dummy molecularly imprinted polymers-capped CdTe quantum dots for the fluorescent
      sensing of 2,4,6-trinitrotoluene.
AB  - Molecularly imprinted polymers (MIPs) with trinitrophenol (TNP) as a dummy
      template molecule capped with CdTe quantum dots (QDs) were prepared using 3
      aminopropyltriethoxy silane (APTES) as the functional monomer and
      tetraethoxysilane (TEOS) as the cross linker through a seed-growth method via a
      sol-gel process (i.e., DMIP@QDs) for the sensing of 2,4,6-trinitrotoluene (TNT)
      on the basis of electron-transfer-induced fluorescence quenching. With the
      presence and increase of TNT in sample solutions, a Meisenheimer complex was
      formed between TNT and the primary amino groups on the surface of the QDs. The
      energy of the QDs was transferred to the complex, resulting in the quenching of
      the QDs and thus decreasing the fluorescence intensity, which allowed the TNT to
      be sensed optically. DMIP@QDs generated a significantly reduced fluorescent
      intensity within less than 10 min upon binding TNT. The fluorescence-quenching
      fractions of the sensor presented a satisfactory linearity with TNT
      concentrations in the range of 0.8-30 MUM, and its limit of detection could reach
      0.28 MUM. The sensor exhibited distinguished selectivity and a high binding
      affinity to TNT over its possibly competing molecules of 2,4-dinitrophenol (DNP),
      4-nitrophenol (4-NP), phenol, and dinitrotoluene (DNT) because there are more
      nitro groups in TNT and therefore a stronger electron-withdrawing ability and
      because it has a high similarity in shape and volume to TNP. The sensor was
      successfully applied to determine the amount of TNT in soil samples, and the
      average recoveries of TNT at three spiking levels ranged from 90.3 to 97.8% with
      relative standard deviations below 5.12%. The results provided an effective way
      to develop sensors for the rapid recognition and determination of hazardous
      materials from complex matrices. 

PMID- 23876062
TI  - A phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo
      for treatment of locally advanced or metastatIc HER2-Negative breast CancEr (the
      RESILIENCE study): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Sorafenib is an oral multikinase inhibitor with
      antiangiogenic/antiproliferative activity. A randomized phase 2b screening trial
      in human epidermal growth factor receptor 2 (HER2)-negative advanced breast
      cancer demonstrated a significant improvement in progression-free survival (PFS)
      when sorafenib was added to capecitabine versus placebo (median 6.4 versus 4.1
      months; hazard ratio = 0.58; P = 0.001). Most drug-related adverse events were
      Grade 1/2 in severity with the exception of Grade 3 hand-foot skin
      reaction/syndrome (44% versus 14%, respectively). These results suggest a role
      for the combination of sorafenib and capecitabine in breast cancer and supported
      a phase 3 confirmatory trial. Here we describe RESILIENCE - a multinational,
      double-blind, randomized, placebo-controlled, phase 3 trial - assessing the
      addition of sorafenib to first- or second-line capecitabine in advanced HER2
      negative breast cancer. METHODS/DESIGN: Eligibility criteria include >=18 years
      of age, <=1 prior chemotherapy regimen for metastatic disease, and resistant
      to/failed taxane and anthracycline or no indication for further anthracycline.
      Prior treatment with a vascular endothelial growth factor inhibitor is not
      allowed. Patients with significant cardiovascular disease or active brain
      metastases are not eligible. Patients are stratified by hormone-receptor status,
      geographic region, and prior metastatic chemotherapy status and randomized (1:1)
      to capecitabine (1000 mg/m2 orally twice daily (BID), days 1 to 14 of 21) in
      combination with sorafenib (orally BID, days 1 to 21, total dose 600 mg/day) or
      matching placebo. Capecitabine and sorafenib/placebo doses can be escalated to
      1250 mg/m2 BID and 400 mg BID, respectively, as tolerated, or reduced to manage
      toxicity. Dose re-escalation after a reduction is allowed for sorafenib/placebo
      but not for capecitabine. This dosing algorithm was designed to mitigate
      dermatologic and other toxicity, in addition to detailed guidelines for
      prophylactic and symptomatic treatment. Radiographic assessment is every 6 weeks
      for 36 weeks, and every 9 weeks thereafter. The primary endpoint is PFS by
      blinded independent central review (Response Evaluation Criteria in Solid Tumors
      1.1 criteria). Secondary endpoints include overall survival, time to progression,
      overall response rate, duration of response, and safety. Enrollment began in
      November 2010 with a target of approximately 519 patients. DISCUSSION: RESILIENCE
      will provide definitive PFS data for the combination of sorafenib and
      capecitabine in advanced HER2-negative breast cancer and better characterize the
      benefit-to-risk profile. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01234337.

PMID- 23876064
TI  - Accommodating families during a child's hospital stay: implications for family
      experience and perceptions of outcomes.
AB  - Family accommodation programs, such as Ronald McDonald House(r) (RMH), aim to
      facilitate family proximity and family-centered care during a child's
      hospitalization, yet little is known about how the programs influence family
      experience. The aim of this study was to investigate the perspectives of families
      regarding the impact of the RMH stay on the family and their hospital experience
      and to explore the influence of demographic and clinical factors on family member
      views about their experience and outcome of their child's hospitalization. Family
      members who spent one or more nights at an RMH in Southern California completed a
      cross-sectional, self-report survey that included descriptive information about
      the family and the hospital experience. The 2,081 respondents (53% mothers, 24%
      fathers, 7% other family members, and 15% multiple family members) generally
      reported positive experiences at RMH. Although effect sizes were small, families
      who stayed together for at least a portion of their stay believed more strongly
      that their ability to stay nearby improved their child's recovery and that RMH
      helped their family to stay together. Cultural differences were also evident,
      with Hispanic families believing more strongly that RMH shortened their child's
      hospital stay. A family's ability to stay together and in close proximity during
      a pediatric hospital stay is facilitated by accommodations such as RMH and
      provides important benefits in terms of family experience, psychosocial well
      being, and perceptions of child recovery. These services also contribute
      meaningfully to the priority of providing family-centered care.

PMID- 23876065
TI  - Pimecrolimus, a topical calcineurin inhibitor used in the treatment of atopic
      eczema.
AB  - INTRODUCTION: Pimecrolimus , a calcineurin inhibitor, is a non-steroidal
      treatment option in patients aged >= 2 years with mild-to-moderate atopic eczema
      (AE). It was approved as a viable therapeutic option by the FDA in 2001 and in
      the European Union a year later in 2002. Calcineurin inhibitors inhibit the
      synthesis of inflammatory cytokines released from T cells and mast cells. In
      contrast to corticosteroids, calcineurin inhibitors act specifically on
      proinflammatory cells. Pimecrolimus shows comparative efficacy to mild topical
      corticosteroids and a special antipruritic effect. Furthermore, examinations of
      the systemic absorption of pimecrolimus implicated no systemic immunosuppression.
      In 2006, the FDA set a black box warning in the packaging materials of
      pimecrolimus alluding to the risk of skin malignancy or lymphomas due to
      theoretical consideration. AREAS COVERED: The authors provide a review of
      pimecrolimus as a treatment for AE. Specifically, the authors present the
      pharmacokinetic and pharmacodynamic information on pimecrolimus and also review
      its efficacy. The authors also discuss pimecrolimus' safety and tolerability
      profile. EXPERT OPINION: Pimecrolimus represents a valuable part of active and
      proactive therapy in AE. That being said, the long-term safety of topical
      calcineurin inhibitors remains to be investigated. Given the results from
      experimental photocarcinogenicity studies, effective sun protection should be
      employed during the therapy, although an increased risk for skin malignancies and
      lymphomas was not found in recent studies. Pimecrolimus should be considered as
      an alternative therapeutic approach in AE treatment management going along with a
      corticoid-sparing effect.

PMID- 23876066
TI  - Caffeic acid phenethyl ester inhibits alpha-melanocyte stimulating hormone
      induced melanin synthesis through suppressing transactivation activity of
      microphthalmia-associated transcription factor.
AB  - Caffeic acid phenethyl ester (1), a natural compound found in various plants and
      propolis, is a well-known anti-inflammatory, immunomodulatory, and cytotoxic
      agent. The present study aimed to investigate the molecular events underlying the
      antimelanogenic activity of 1 in alpha-melanocyte stimulating hormone (alpha-MSH)
      stimulated B16-F10 melanoma cells. In this investigation, 1 effectively reduced
      alpha-MSH-stimulated melanin synthesis by suppressing expression of melanogenic
      enzymes such as tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase
      related protein-2 (TRP-2), although this compound did not directly inhibit
      tyrosinase enzyme activity. On the other hand, the expression and nuclear
      translocation of microphthalmia-associated transcription factor (MITF) as a key
      transcription factor for tyrosinase expression regulating melanogenesis were not
      affected by treatment with 1. The upstream signaling pathways including cAMP
      response element-binding protein (CREB), glycogen synthase kinase-3beta (GSK
      3beta), and Akt for activation and expression of MITF were also not influenced by
      1. Interestingly, 1 inhibited transcriptional activity of a tyrosinase promoter
      by suppressing the interaction of MITF protein with an M-box containing a CATGTG
      motif on the tyrosinase promoter. Given the important role of MITF in
      melanogenesis, suppression of 1 on the function of MITF to transactivate
      tyrosinase promoter may present a novel therapeutic approach to treat
      hyperpigmentation disorders. 

PMID- 23876067
TI  - Systematic review and meta-analysis of the effectiveness of continuous glucose
      monitoring (CGM) on glucose control in diabetes.
AB  - Diabetes mellitus is a chronic disease that necessitates continuing treatment and
      patient self-care education. Monitoring of blood glucose to near normal level
      without hypoglycemia becomes a challenge in the management of diabetes. Although
      self monitoring of blood glucose (SMBG) can provide daily monitoring of blood
      glucose level and help to adjust therapy, it cannot detect hypoglycemic
      unawareness and nocturnal hypoglycemia which occurred mostly in T1DM pediatrics.
      Continuous glucose monitoring (CGM) offers continuous glucose data every 5
      minutes to adjust insulin therapy especially for T1DM patients and to monitor
      lifestyle intervention especially for T2DM patients by care providers or even
      patients themselves. The main objective of this study was to assess the effects
      of continuous glucose monitoring (CGM) on glycemic control in Type 1 diabetic
      pediatrics and Type 2 diabetic adults by collecting randomized controlled trials
      from MEDLINE (pubmed), SCOPUS, CINAHL, Web of Science and The Cochrane Library up
      to May 2013 and historical search through the reference lists of relevant
      articles. There are two types of CGM device: real-time CGM and retrospective CGM
      and both types of the device were included in the analysis. In T1DM pediatrics,
      CGM use was no more effective than SMBG in reducing HbA1c [mean difference -
      0.13% (95% CI -0.38% to 0.11%,]. This effect was independent of HbA1c level at
      baseline. Subgroup analysis indicated that retrospective CGM was not superior to
      SMBG [mean difference -0.05% (95% CI -0.46% to 0.35%)]. In contrast, real-time
      CGM revealed better effect in lowering HbA1c level compared with SMBG [mean
      difference -0.18% (95% CI -0.35% to -0.02%, p = 0.02)]. In T2DM adults,
      significant reduction in HbA1c level was detected with CGM compared with SMBG
      [mean difference - 0.31% (95% CI -0.6% to -0.02%, p = 0.04)]. This systematic
      review and meta-analysis suggested that real-time CGM can be more effective than
      SMBG in T1DM pediatrics, though retrospective CGM was not. CGM provided better
      glycemic control in T2DM adults compared with SMBG. 

PMID- 23876068
TI  - Recovery of isoflavone aglycones from soy whey wastewater using foam
      fractionation and acidic hydrolysis.
AB  - The purpose of this work was to recover isoflavone aglycones from industrial soy
      whey wastewater, where the isoflavone aglycones mainly existed in the form of
      beta-glycosides. First, foam fractionation was used for effectively concentrating
      the total soy isoflavones, including isoflavone aglycones and beta-glycosides,
      from the wastewater. Fourier transform infrared spectroscopy indicated the
      existence of complexes of soy isoflavones and soy proteins. When soy proteins
      were used as the collectors, a high enrichment ratio of 3.68 was obtained under
      the optimal operating conditions of temperature of 50  degrees C, pH of 5.0,
      volumetric air flow rate of 100 mL/min, and loading liquid height of 400 mm.
      Subsequently, acidic hydrolysis was used for hydrolyzing beta-glycosides in the
      foamate into aglycones. Using response surface methodology, a hydrolytic
      percentage could reach 96% under the optimum hydrolysis conditions of hydrolytic
      temperature of 80  degrees C, hydrochloric acid concentration of 1.37 mol/L, and
      hydrolytic time of 90 min. 

PMID- 23876069
TI  - Overview of lupus nephritis management guidelines and perspective from Asia.
AB  - Lupus nephritis (LN) is a common and important manifestation of systemic lupus
      erythematosus (SLE). Evidence suggests higher rates of lupus renal involvement in
      Asian populations, and maybe more severe nephritis, compared with other racial or
      ethnic groups. The management of LN has evolved considerably over the past three
      decades, based on observations from clinical studies that investigated different
      immunosuppressive agents including corticosteroids, cyclophosphamide,
      azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic
      therapies. This is accompanied by improvements in both the short-term treatment
      response rate and long-term renal function preservation. Treatment guidelines for
      LN have recently been issued by rheumatology and nephrology communities in U.S.A.
      and Europe. In view of the racial difference in disease manifestation and
      response to therapy, and the substantial disease burden in Asia, a panel of 15
      nephrologists and rheumatologists from different Asian regions with extensive
      experience in lupus nephritis - the Steering Group for the Asian Lupus Nephritis
      Network (ALNN) - met and discussed the management of lupus nephritis in Asian
      patients. The group has also reviewed and deliberated on the recently published
      recommendations from other parts of the world. This manuscript summarizes the
      discussions by the group and presents consensus views on the clinical management
      and treatment of adult Asian patients with LN, taking into account both the
      available evidence and expert opinion in areas where evidence remains to be
      sought. 

PMID- 23876070
TI  - Fine particulate air pollution and hospital admissions for congestive heart
      failure: a case-crossover study in Taipei.
AB  - This study was undertaken to determine whether there was an association between
      fine particles (PM2.5) levels and hospital admissions for congestive heart
      failure (CHF) in Taipei, Taiwan. Hospital admissions for CHF and ambient air
      pollution data for Taipei were obtained for the period 2006-2010. The relative
      risk of hospital admissions was estimated using a case-crossover approach,
      controlling for weather variables, day of the week, seasonality and long-term
      time trends. For the single pollutant model (without adjustment for other
      pollutants), increased CHF admissions were significantly associated with PM2.5
      both on warm days (>23  degrees C) and cool days (<23  degrees C), with an
      interquartile range increase associated with a 13% (95% CI = 9-17%) and 3% (95%
      CI = 0-7%) increase in CHF admissions, respectively. In the two-pollutant models,
      PM2.5 remained significant after the inclusion of SO2 or O3 both on warm and cool
      days. This study provides evidence that higher levels of PM2.5 increase the risk
      of hospital admissions for CHF.

PMID- 23876071
TI  - Inferring frail life expectancies in Chicago from daily fluctuations in elderly
      mortality.
AB  - Susceptible sub-populations with existing disease have exhibited stronger
      relationships between air quality and mortality in time-series studies, but their
      associated life expectancies have largely been overlooked. Murray and Nelson
      developed a new time-series model that estimated a small unobserved (frail) sub
      population and their resulting life expectancies in Philadelphia, including
      environment relationships. As a further example in a different geographic area,
      we used this model with 1987-2000 daily mortality data in Chicago and found a
      stable frail population at risk of ~900 persons with a mean life expectancy of
      ~11 days; fewer than two daily deaths were associated with air pollution. We
      considered daily concentrations of CO, NO2, O3, PM10 and SO2, and found PM10 and
      O3 to have stronger associations with frail mortality. Our estimates of life
      expectancy and air pollution and temperature relationships are similar to those
      found in other studies that used different methods. Temperature was more
      important than air pollution during the 1995 heat wave, when mortality risks
      increased dramatically after 2 d exposure and life expectancies decreased to 3-5
      d. Modeling this event separately had substantial effects on lagged mortality-
      air pollution relationships and the population at risk. The premises of the
      Murray-Nelson model were supported by simultaneously considering an additional
      subgroup of non-frail individuals; they contributed only ~1% of total elderly
      deaths. We conclude that frail life expectancies estimated by the Murray-Nelson
      model are robust, and that under these conditions non-frail persons have little
      risk of acute mortality, with or without contributions from air pollution.

PMID- 23876072
TI  - Puzzling polymorphism of layered Ba(CoPO4)2.
AB  - In this paper, we present the phase diagram and magnetic properties of the
      layered Co(2+)-based compounds of formula Ba(CoPO4)2 for which the rhombohedral
      gamma form is well-known for its quasi-2D XY topology that is responsible for
      magnetization steps. The structural resolution of the new, room temperature
      stable monoclinic alpha form shows similitude with the hydrated homologue
      Ba(CoPO4)2.H2O and consists of the stacking between [CoPO4](-) sheets with chain
      subunits. We show by means of high temperature powder XRD and thermal analyses
      that the alpha form transforms into several polymorphs also exhibiting layered
      architectures upon heating. Three reversible transitions at 773, 893, and 993 K
      were observed from DTA which allowed us to define several forms as follows: alpha
      -> alpha' -> alpha" -> beta. The crystallographic relationships between the
      several polymorphs and hydrate analogue are discussed. The alpha' and alpha" cell
      parameters involve a direct relationship with the alpha form, whereas the
      trigonal beta phase was fully solved and found isomorphic with the compounds
      CaZn2P2O8 and BaAl2Si2O8. The magnetic study of the alpha form shows an
      antiferromagnetic ordering at T(N) = 17 K, with spins canting below T(N). Then,
      the analysis of the magnetic interactions paths occurring within the layers
      evidence superexchange paths and additional supersuperexchange paths between the
      chains. This scheme leads to a hexagonal frustrated topology responsible for the
      canted spin structure in a 2D-topology of anisotropic Co(2+) magnetic ions.

PMID- 23876073
TI  - How will biotic interactions influence climate change-induced range shifts?
AB  - Biotic interactions present a challenge in determining whether species
      distributions will track climate change. Interactions with competitors,
      consumers, mutualists, and facilitators can strongly influence local species
      distributions, but few studies assess how and whether these interactions will
      impede or accelerate climate change-induced range shifts. In this paper, we
      explore how ecologists might move forward on this question. We first outline the
      conditions under which biotic interactions can result in range shifts that
      proceed faster or slower than climate velocity and result in ecological
      surprises. Next, we use our own work to demonstrate that experimental studies
      documenting the strength of biotic interactions across large environmental
      gradients are a critical first step for understanding whether they will influence
      climate change-induced range shifts. Further progress could be made by
      integrating results from these studies into modeling frameworks to predict how or
      generalize when biotic interactions mediate how changing climates influence range
      shifts. Finally, we argue that many more case studies like those described here
      are needed to explore the importance of biotic interactions during climate change
      induced range shifts. 

PMID- 23876075
TI  - Humanitarian agencies and authoritarian states: a symbiotic relationship?
AB  - The relationship between humanitarian agencies and authoritarian states is of
      growing concern to Medecins Sans Frontieres (MSF), given the recurring
      difficulties experienced in negotiating access and implementing operations in
      such contexts. The effort to negotiate and gain approval from states to operate
      on their territory prompts reflection on the sources of legitimacy for action.
      Drawing on direct field examples in two countries only very rarely examined-
      Turkmenistan and Uzbekistan--this paper explores MSF's attempts to offer live
      saving medical care there. It shows that successful access negotiations hinged
      heavily on demonstrating added value (medical relevance) while simultaneously
      building relationships with authorities, identifying possible allies within
      health ministries, and hoping that such measures could promote a level of
      acceptance or trust needed to operate. It is clear that the operational space
      achieved is bound to remain limited and fragile, and that many compromises have
      to be considered and judged against ethical principles and the overall impact of
      the intervention.

PMID- 23876074
TI  - A large QTL for fear and anxiety mapped using an F2 cross can be dissected into
      multiple smaller QTLs.
AB  - Using chromosome substitution strains (CSS), we previously identified a large
      quantitative trait locus (QTL) for conditioned fear (CF) on mouse chromosome 10.
      Here, we used an F2 cross between CSS-10 and C57BL/6J (B6) to localize that QTL
      to distal chromosome 10. That QTL accounted for all the difference between CSS-10
      and B6. We then produced congenic strains to fine-map that interval. We
      identified two congenic strains that captured some or all the QTL. The larger
      congenic strain (Line 1: 122.387121-129.068 Mb; build 37) appeared to account for
      all the difference between CSS-10 and B6. The smaller congenic strain (Line 2:
      127.277-129.068 Mb) was intermediate between CSS-10 and B6. We used haplotype
      mapping followed by quantitative polymerase chain reaction to identify one gene
      that was differentially expressed in both lines relative to B6 (Rnf41) and one
      that was differentially expressed between only Line 1 and B6 (Shmt2). These cis
      eQTLs may cause the behavioral QTLs; however, further studies are required to
      validate these candidate genes. More generally, our observation that a large QTL
      mapped using CSS and F2 crosses can be dissected into multiple smaller QTLs shows
      a weaknesses of two-stage approaches that seek to use coarse mapping to identify
      large regions followed by fine-mapping. Indeed, additional dissection of these
      congenic strains might result in further subdivision of these QTL regions.
      Despite these limitations, we have successfully fine-mapped two QTLs to small
      regions and identified putative candidate genes, showing that the congenic
      approach can be effective for fine-mapping QTLs. 

PMID- 23876076
TI  - Bovine model of chronic ischemic cardiomyopathy: implications for ventricular
      assist device research.
AB  - Ventricular assist devices (VADs) have emerged as a successful treatment option
      for advanced heart failure. The objective of this study was to develop a
      clinically relevant model of chronic ischemic cardiomyopathy to investigate
      functional, histological, and molecular changes during mechanical circulatory
      support. In calves (n = 17, 94 +/- 7 kg), 90 MUm microspheres were injected
      percutaneously into the left coronary artery. Serial echocardiography was
      performed weekly to evaluate cardiac function. Sixty days after coronary
      microembolization, a terminal study was performed via thoracotomy to measure
      hemodynamics. Regional myocardial and end-organ blood flows were quantified with
      15-MUm fluorescent-labeled microspheres. Myocardial fibrosis, myocyte size, and
      myocardial apoptosis were quantified with histological stains. Eleven animals
      survived coronary microembolization and exhibited clinical and statistically
      significant echocardiographic and hemodynamic signs of severe systolic
      dysfunction. Statistically significant decreases in regional myocardial blood
      flow and increases in myocardial fibrosis, myocyte size, total myocardial
      apoptosis, and cardiac myocyte-specific apoptosis were observed. End-organ
      hypoperfusion was observed. Coronary microembolization induced stable and
      reproducible chronic left ventricular failure in calves. The anatomical size and
      physiology of the bovine heart and thorax are appropriate to study novel
      interventions for the clinical management of heart failure. This model is an
      appropriate physiological substrate in which to test VAD and adjunctive
      biological therapies.

PMID- 23876078
TI  - Cytomegalovirus-related Scleritis.

PMID- 23876077
TI  - Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia
      virus expression in B cells in vitro.
AB  - Programmed death-1 (PD-1) is a known immunoinhibitory receptor that contributes
      to immune evasion of various tumor cells and pathogens causing chronic infection,
      such as bovine leukemia virus (BLV) infection. First, in this study, to establish
      a method for the expression and functional analysis of bovine PD-1, hybridomas
      producing monoclonal antibodies (mAb) specific for bovine PD-1 were established.
      Treatment with these anti-PD-1 mAb enhanced interferon-gamma (IFN-gamma)
      production of bovine peripheral blood mononuclear cells (PBMC). Next, to examine
      whether PD-1 blockade by anti-PD-1 mAb could upregulate the immune reaction
      during chronic infection, the expression and functional analysis of PD-1 in PBMC
      isolated from BLV-infected cattle with or without lymphoma were performed using
      anti-PD-1 mAb. The frequencies of both PD-1+ CD4+ T cells in blood and lymph node
      and PD-1+ CD8+ T cells in lymph node were higher in BLV-infected cattle with
      lymphoma than those without lymphoma or control uninfected cattle. PD-1 blockade
      enhanced IFN-gamma production and proliferation and reduced BLV-gp51 expression
      and B-cell activation in PBMC from BLV-infected cattle in response to BLV-gp51
      peptide mixture. These data show that anti-bovine PD-1 mAb could provide a new
      therapy to control BLV infection via upregulation of immune response. 

PMID- 23876080
TI  - Formation of methyl radicals from decomposition of methyl-substituted silanes
      over tungsten and tantalum filament surfaces.
AB  - The formation of methyl radical from the decomposition of four methyl-substituted
      silane molecules, including monomethylsilane (MMS), dimethylsilane (DMS),
      trimethylsilane (TriMS), and tetramethylsilane (TMS), over tungsten and tantalum
      filament surfaces has been systematically studied using vacuum ultraviolet laser
      ionization mass spectrometry. The methyl radical intensity increases with
      temperature for both filaments in the low-temperature region; however, beyond the
      optimum temperature, a gradual decrease in the methyl intensity was observed for
      MMS, DMS, and TriMS when using Ta, whereas the intensity reaches a plateau with
      W. This is due to the fact that Ta is more efficient in releasing surface-bound H
      and forming active sites, leading to the adsorption of methyl radicals on the
      metal surface in the high-temperature regions. The apparent activation energy for
      methyl radical formation from the dissociation of MMS, DMS, TriMS, and TMS
      molecules on both W and Ta filaments increases with the increasing number of
      methyl substitution. The dissociation process is believed to be initiated by the
      Si-H bond cleavage and followed by Si-CH3 bond breaking. The obtained low
      activation energy values for methyl radical formation in the range of 51.1-84.7
      kJ.mol(-1) suggest that the ejection of CH3 radicals is accompanied by the
      formation of a Si moiety bound to the metal surface. Overall, TMS produces the
      least number of methyl radicals on both filaments with the highest activation
      energy. The numbers of methyl radicals produced when using MMS, DMS, and TriMS
      are similar, but MMS gives the lowest activation energy. 

PMID- 23876079
TI  - Local illness concepts and their relevance for the prevention and control of
      malaria during pregnancy in Ghana, Kenya and Malawi: findings from a comparative
      qualitative study.
AB  - BACKGROUND: In sub-Saharan Africa, the burden of morbidity and mortality linked
      to malaria during pregnancy (MiP) is significant and compounded by its unclear
      symptoms and links with other health problems during pregnancy. Mindful of the
      biomedical and social complexity of MiP, this article explores and compares local
      understandings of MiP and their links with other pregnancy-related health
      problems. METHODS: A comparative qualitative study was undertaken at four sites
      in three countries: Ghana, Malawi and Kenya. Individual and group interviews were
      conducted with pregnant women, their relatives, opinion leaders, other community
      members and health providers. MiP-related behaviours were also observed at health
      facilities and in local communities. RESULTS: Across the four sites, local
      malaria concepts overlapped with biomedically defined malaria. In terms of
      symptoms, at-risk groups, outcomes and aetiology of malaria during pregnancy,
      this overlap was however both site-specific and partial. Moreover, the local
      malaria concepts were not monolithic and their descriptions varied amongst
      respondents. The symptoms of pregnancy and malaria also overlapped but, for
      respondents, symptom severity was the distinguishing factor. Malaria was
      generally, though not universally, perceived as serious for pregnant women.
      Miscarriage was the most widely known outcome, and links with anaemia, low birth
      weight and congenital malaria were mentioned. Nonetheless, amongst many potential
      causes of miscarriage, malaria was not recognized as the most important, but
      rather interacted with other pregnancy-related problems. CONCLUSIONS: Given the
      overlap of common pregnancy problems with the symptoms of malaria, and the
      limited association of malaria with its main outcomes, a comprehensive antenatal
      care programme is the most appropriate strategy for the provision of health
      education, prevention and treatment for MiP. Variations in locally shared
      understandings of MiP must however be taken into account when designing and
      promoting MiP intervention strategies.

PMID- 23876081
TI  - Calcified, minimally fat-contained angiomyolipoma clinically indistinguishable
      from a renal cell carcinoma.
AB  - BACKGROUND: Angiomyolipomas are benign tumors of the kidney. Typical
      angiomyolipomas are usually recognized by identifying fat components before any
      intervention. On the contrary, solid renal masses without evident fatty
      components but containing calcifications on the computed tomography scan are
      suspicious for malignancy. However, as in this rare case, rules of diagnostic
      imaging are of exceptions. CASE PRESENTATION: A 40-year-old man presented with
      left flank pain. The plain X-ray showed multiple coarse calcifications of 4.0x3.2
      cm in diameter on the left upper quadrant abdomen. Computed tomography scan
      further revealed a solid renal mass and inside the mass there were
      calcifications. The size of the tumor was 5.6*5.5*6.3 cm. We performed a radical
      nephrectomy, and the histopathology showed a minimally fat-contained
      angiomyolipoma of multiple calcifications. The patient was free of recurrence or
      metastases after a follow-up period of 3 years. CONCLUSION: An angiomyolipoma
      containing calcification is rare. An angiomyolipoma with minimal fat concomitant
      with calcifications is an even rarer presentation. It is very difficult to
      differentiate a minimal-fat angiomyolipoma with calcifications from a renal cell
      carcinoma preoperatively. In such a circumstance, a well-planned partial
      nephrectomy may be optimal for the patient, regardless of the tumor size.

PMID- 23876082
TI  - Realizing molecular pixel system for full-color fluorescence reproduction: RGB
      emitting molecular mixture free from energy transfer crosstalk.
AB  - A full-color molecular pixel system is realized for the first time using simple
      mixtures composed of RGB-emitting excited-state intramolecular proton transfer
      (ESIPT) dyes, each of which has delicately tailored Stokes shift and independent
      emission capability completely free from energy transfer crosstalk between them.
      It is demonstrated that the whole range of emission colors enclosed within the
      RGB color triangle on the CIE 1931 diagram is predictable and conveniently
      reproducible from the RGB molecular pixels not only in the solution but also in
      the polymer film. It must be noted that mixing ratios to reproduce the desired
      color coordinates can be precisely calculated on the basis of additive color
      theory according to their molecular pixel behavior. 

PMID- 23876083
TI  - Protective effect of rutin on hexachlorobutadiene-induced nephrotoxicity.
AB  - Hexachlorobutadiene (HCBD) is a potent nephrotoxin which nowadays contaminates
      human foods and water. On the other hands, it has been reported that rutin is a
      chemopreventive flavonoid which exerts some protective effects on the kidney.
      Therefore, in this work, the possible effect of rutin on HCBD-induced
      nephrotoxicity was investigated in female rats. The animals were divided into
      five groups. Groups 1 and 2 were treated with vehicle and HCBD (100 mg/kg, i.p.),
      respectively. Groups 3-5 were pretreated with rutin (100, 500 and 1000 mg/kg,
      i.p.) 1 h before HCBD injection. The level of serum urea and creatinine as well
      as urinary glucose and protein were measured. Total thiol content and lipid
      peroxidation level were also determined in the kidney homogenate. When compared
      to control group, a significant increase in the level of serum creatinine and
      urea (p < 0.001) as well as urine glucose and protein (p < 0.001) were observed
      after 24 h of HCBD administration. HCBD also caused a significant decrease in
      total thiol content (p < 0.001) and a significant increase in lipid peroxidation
      level (p < 0.001). Pretreatment with rutin could decrease serum creatinine (p <
      0.001) and urea (p < 0.001) as well as urine protein (p < 0.001) concentrations
      when compared with HCBD treated rats. No significant modification on urine
      glucose was seen (p > 0.05). Rutin also reversed the HCBD-induced depletion in
      thiol content (p < 0.001) and elevation in lipid peroxidation (p < 0.001) in the
      kidney. The results of present study showed that rutin clearly attenuated HCBD
      induced nephrotoxicity and has the potential to be considered as a
      nephroprotective agent.

PMID- 23876084
TI  - Comparisons of the morbidity outcomes in repeated cesarean sections using midline
      and Pfannenstiel incisions.
AB  - AIM: The aim of this study was to evaluate operative complications, operative
      time, postpartum complications and neonatal outcome in repeated cesarean section
      between previous low midline and previous Pfannenstiel cesarean section. MATERIAL
      AND METHODS: This was a prospective comparative study conducted at the King
      Chulalongkorn Memorial Hospital in pregnant women with indication of repeated
      cesarean section for either low midline or Pfannenstiel incisions. RESULTS: A
      total of 320 pregnant women with previous cesarean section were enrolled into two
      groups: low midline (n = 160) and Pfannenstiel (n = 160) groups. Operative
      complications, postpartum complications and neonatal outcomes were not
      statistically different between the groups (P > 0.05). Median times for total
      operative time (50 vs 50 min, P = 0.833), time from skin incision to the uterus
      (4 vs 4 min, P = 0.877), and time from uterine incision to fetal delivery (3 vs 2
      min, P = 0.871) were comparable between the groups. CONCLUSIONS: Operative
      complications, operative time, postpartum complications and neonatal outcomes
      were comparable between low midline and Pfannenstiel groups in repeated cesarean
      sections irrespective of the previous technique used.

PMID- 23876086
TI  - Transportation vulnerability as a barrier to service utilization for HIV-positive
      individuals.
AB  - Research suggests that transportation vulnerability can negatively impact
      adherence to HIV-related medical treatment. Moreover, transportation can be a
      barrier to accessing ancillary services which can increase positive health
      outcomes for HIV-positive individuals. This study examines transportation
      vulnerability and its impact on HIV-related health and ancillary service
      utilization in the Mid-South Region. Focus groups and interviews were conducted
      with service providers and HIV-positive individuals, and survey data were
      collected from HIV-positive individuals (N=309) using the five A's of access to
      frame transportation vulnerability: availability, accessibility, accommodation,
      affordability, and acceptability. Study results indicate that transportation
      vulnerability can present significant barriers to service utilization for HIV
      positive individuals, including insufficient transportation infrastructure,
      incompatible fit between transportation and health systems, and insensitivity to
      privacy issues. One consequence of transportation vulnerability is reliance upon
      weaving together multiple modes of transport to access care and ancillary
      services, creating additional barriers to service utilization and medical
      adherence. The research team recommends more investment in public transit
      systems, expanded services, and innovative approaches to solving procedural
      problems.

PMID- 23876087
TI  - Spontaneous formation of stringlike clusters and smectic sheets for colloidal
      rods confined in thin wedgelike gaps.
AB  - Monodispersed colloidal rods of beta-FeOOH with sizes ranging from 270 to 580 nm
      in length and 50 to 80 nm in width were synthesized. Narrow wedgelike gaps (0 to
      700 nm in height) were formed around the inner bottom edge of the suspension
      glass cells. Optical microscopic observations revealed the formation of
      stringlike clusters of the rods and smectic sheets (by spontaneous side-by-side
      clustering of the strings) in the isotropic phase of the rod suspensions confined
      in narrow gaps; the electrolyte (HCl) concentrations of the suspensions are 5-40
      mM, at which inter-rod interactions are attractive. The strings exhibit different
      colors that were used to investigate the structures of the strings with the help
      of interference color theory for thin films. The results are as follows. (1) The
      rods, lying flat on the gap bottom, are connected side-by-side and stacked upward
      to form stringlike clusters with different thicknesses depending on the gap
      height. (2) The stacking numbers (N(sr)) of the rods are estimated to be 1-5.
      With N(sr) increasing from 2 to 5, the volume fractions (phi) of the rods in the
      strings increased typically from 0.25-0.3 to 0.35-0.42 to reach limiting values
      (close to the phi values of the rods in the bulk smectic phase). (3) Unexpected
      low-phi strings are found in regions with an intermediate height in the gaps.
      These behaviors of phi may be caused by thermal fluctuations of the strings.

PMID- 23876088
TI  - Comprehensive analyses of microRNA gene evolution in paleopolyploid soybean
      genome.
AB  - miRNA genes are thought to undergo quick birth and death processes in genomes and
      the emergence of a MIRNA-like hairpin provides the base for functional miRNA gene
      formation. However, the factors affecting the formation of an active miRNA gene
      from a MIRNA-like hairpin within a genome remain unclear. We performed a genome
      wide investigation of MIRNA-like hairpin accumulation, expression, structural
      changes and relationships with annotated genomic features in the paleopolyploid
      soybean genome. Our results showed that adjacent gene and transposable element
      content, rates of genetic recombination at location of emergence, along with its
      own gene structure divergence greatly affected miRNA gene evolution. Further
      investigation suggested that miRNA genes from different duplication sources
      followed distinct evolutionary trajectories and that the accumulation of MIRNA
      like hairpins might be an important factor in causing long terminal repeat
      retrotransposons to lose activity during genome evolution. 

PMID- 23876085
TI  - The impact of neuroimmune changes on development of amyloid pathology; relevance
      to Alzheimer's disease.
AB  - Neuroinflammatory changes are a characteristic of several, if not all,
      neurodegenerative diseases including Alzheimer's disease and are typified by
      increased microglial activation. Microglia express several receptors making them
      highly reactive and plastic cells, and, at least in vitro, they adopt different
      phenotypes in a manner analogous to their peripheral counterparts, macrophages.
      Microglia also express numerous cell surface proteins enabling them to interact
      with cells and the evidence indicates that maintenance of microglia in a
      quiescent state relies, at least to some extent, on an interaction with neurons
      by means of specific ligand-receptor pairs, for example CD200-CD200R. It is clear
      that microglia also interact with T cells and recent evidence indicates that co
      incubation of microglia with T helper type 1 cells markedly increases their
      activation. Under normal conditions, small numbers of activated T cells gain
      entry to the brain and are involved in immune surveillance but infiltration of
      significant numbers of T cells occurs in disease and following injury. The
      consequences of T cell infiltration appear to depend on the conditions, with
      descriptions of both neurodestructive and neuroprotective effects in animal
      models of different diseases. This review will discuss the modulatory effect of T
      cells on microglia and the impact of infiltration of T cells into the brain with
      a focus on Alzheimer's disease, and will propose that infiltration of interferon
      gamma-producing cells may be an important factor in triggering inflammation that
      is pathogenic and destructive.

PMID- 23876089
TI  - Malonic acid half oxyesters and thioesters: solvent-free synthesis and DFT
      analysis of their enols.
AB  - A much improved synthetic route to malonic acid half thioesters (MAHTs) and
      oxyesters (MAHOs), the easy incorporation of deuterium labeling expecially in
      MAHTs, and an unexpectedly large difference in enolization chemistry between
      MAHTs and MAHOs are reported. Density functional theory calculations explore the
      origins of this difference and identify an additional MAHT molecular orbital
      which increases delocalization between sulfur and the enol in both cisoid and
      transoid forms. 

PMID- 23876090
TI  - Update on statins: hope for osteoporotic fracture healing treatment.
AB  - Fracture healing is a process of recovering injured bone tissue forms and
      functions. Osteoporosis can delay the healing process, which contributes to
      personal suffering and loss of activities. Osteoporosis patients tend to lose
      bone mass at the metaphyseal region which require treatment to increase bone
      mass. Postmenopausal osteoporosis is the most common osteoporosis that occurs in
      women which subsequently resulted in fractures even under slight trauma. Estrogen
      Replacement Therapy (ERT), the recommended therapy for postmenopausal
      osteoporosis, is associated with higher risk of breast cancer, ovarian cancer and
      cardiovascular diseases. As osteoporotic fractures are becoming a public health
      issue, alternative treatment is now being thoroughly explored. The potential
      agent is statins, the HMG-CoA reductase inhibitor which is widely used for
      hypercholesterolemia treatment. Statins have been found to increase bone mass by
      stimulation of Bone morphogenetic protein-2 (BMP-2) expression and Vascular
      Endothelial Growth Factor (VEGF) production. However, these bone forming effects
      were achieved at very high systemic doses. Therefore, studies on locally applied
      statins are required to further explore the ability of statins to stimulate bone
      formation at acceptable doses for better fracture healing. This review highlights
      the animal and clinical studies on fracture healing promotions by statins and the
      mechanisms involved. 

PMID- 23876091
TI  - Does video recording alter the behavior of police during interrogation? A mock
      crime-and-investigation study.
AB  - A field study conducted in a midsized city police department examined whether
      video recording alters the process of interrogation. Sixty-one investigators
      inspected a staged crime scene and interrogated a male mock suspect in sessions
      that were surreptitiously recorded. By random assignment, half the suspects had
      committed the mock crime; the other half were innocent. Half the police
      participants were informed that the sessions were being recorded; half were not.
      Coding of the interrogations revealed the use of several common tactics designed
      to get suspects to confess. Importantly, police in the camera-informed condition
      were less likely than those in the -uninformed condition to use minimization
      tactics and marginally less likely to use maximization tactics. They were also
      perceived by suspects-who were all uninformed of the camera manipulation-as
      trying less hard to elicit a confession. Unanticipated results indicated that
      camera-informed police were better able to discriminate between guilty and
      innocent suspects in their judgments and behavior. The results as a whole
      indicate that video recording can affect the process of interrogation-notably, by
      inhibiting the use of certain tactics. It remains to be seen whether these
      findings generalize to longer and more consequential sessions and whether the
      camera-induced differences found are to be judged as favorable or unfavorable.

PMID- 23876092
TI  - Human matching performance of genuine crime scene latent fingerprints.
AB  - There has been very little research into the nature and development of
      fingerprint matching expertise. Here we present the results of an experiment
      testing the claimed matching expertise of fingerprint examiners. Expert (n = 37),
      intermediate trainee (n = 8), new trainee (n = 9), and novice (n = 37)
      participants performed a fingerprint discrimination task involving genuine crime
      scene latent fingerprints, their matches, and highly similar distractors, in a
      signal detection paradigm. Results show that qualified, court-practicing
      fingerprint experts were exceedingly accurate compared with novices. Experts
      showed a conservative response bias, tending to err on the side of caution by
      making more errors of the sort that could allow a guilty person to escape
      detection than errors of the sort that could falsely incriminate an innocent
      person. The superior performance of experts was not simply a function of their
      ability to match prints, per se, but a result of their ability to identify the
      highly similar, but nonmatching fingerprints as such. Comparing these results
      with previous experiments, experts were even more conservative in their decision
      making when dealing with these genuine crime scene prints than when dealing with
      simulated crime scene prints, and this conservatism made them relatively less
      accurate overall. Intermediate trainees-despite their lack of qualification and
      average 3.5 years experience-performed about as accurately as qualified experts
      who had an average 17.5 years experience. New trainees-despite their 5-week, full
      time training course or their 6 months experience-were not any better than
      novices at discriminating matching and similar nonmatching prints, they were just
      more conservative. Further research is required to determine the precise nature
      of fingerprint matching expertise and the factors that influence performance. The
      findings of this representative, lab-based experiment may have implications for
      the way fingerprint examiners testify in court, but what the findings mean for
      reasoning about expert performance in the wild is an open, empirical, and
      epistemological question.

PMID- 23876093
TI  - What does it mean when age is related to recidivism among sex offenders?
AB  - Age is a robust predictor of recidivism and an item on actuarial tools commonly
      used to predict sexual violent recidivism among sex offenders. However, little is
      known about whether or how much offenders' risk diminishes as a result of aging.
      In the first of two studies, we examined the sexual and violent recidivism of 533
      sex offenders who were over age 50 on release. Age at index offense was at least
      as good at predicting both outcomes as was age at release, and age at index
      offense provided at least as much incremental validity in the prediction of
      violent recidivism to scores on a brief static actuarial tool. Neither age added
      incrementally to static score in the prediction of sexual recidivism. The second
      study examined how well age at first offense, age at index offense, and age at
      release predicted violent recidivism among 527 sex offenders aged 13 to 79 at
      release. Age at first offense predicted best. When age was removed from score on
      the Sex Offender Risk Appraisal Guide, all ages added incrementally but age at
      release least to SORAG score. When participants were divided into quartiles based
      on age at index offense, there was no evidence from any quartile that age at
      release predicted violent recidivism better than age at first offense. The
      authors concluded that age at release is a poor index of within-subject changes
      in risk of sexual or violent recidivism. No adjustment to a sex offender's score
      on a comprehensive actuarial tool that includes age at first or index offense
      should be made simply because the offender is older.

PMID- 23876094
TI  - Cisplatin : an old drug with a newfound efficacy -- from mechanisms of action to
      cytotoxicity.
AB  - INTRODUCTION: Cisplatin is a highly effective antineoplastic drug with an
      extremely current mechanism of action. Cisplatin-induced side effects are dose
      dependent and limit the administration of increased dosages, thus compromising
      its therapeutic efficacy. AREAS COVERED: This review aims to describe the
      emerging knowledge about the biochemical mechanisms that mediate cisplatin
      cytotoxicity and side effects. A specific section is devoted to discuss the
      pathogenesis of cisplatin-related toxicities and the potential measures to
      counteract them. EXPERT OPINION: Although cisplatin has been used for a long
      time, only recently its exact mechanism of action has been better defined. The
      cytotoxic activity of cisplatin is largely dependent on the glycolytic metabolism
      of tumor cells: cisplatin redirects cancer cells to oxidative phosphorylation
      from the 'Warburg effect', which is considered one of the most important
      mechanisms of tumor cell survival. The interference of cisplatin with glucose
      metabolism is also a cause of its relevant toxicities. The emerging knowledge on
      the complex mechanisms, which mediate cisplatin cytotoxicity and side effect, may
      lead to a more appropriate and safe use of this drug. Further studies are
      warranted to define and implement its effectiveness in combination with targeted
      drugs able to interfere with cellular energy metabolism, such as mTOR inhibitors.

PMID- 23876095
TI  - Evaluation of effect of low-level laser therapy on adolescents with
      temporomandibular disorder: study protocol for a randomized controlled trial.
AB  - BACKGROUND: A number of problems involving the temporomandibular joint (TMJ) and
      associated structures can lead to temporomandibular disorder (TMD). The aim of
      the proposed study is to assess the effect of low-level laser therapy on occlusal
      contacts, mandibular movements, electromyography activity in the muscles of
      mastication and pain in adolescents with TMD. METHODS/DESIGN: A randomized,
      controlled, double-blind, clinical trial will be carried out involving 85 male
      and female adolescents between 15 and 18 years of age. The research diagnostic
      criteria for TMD will be used to assess all individuals who agree to participate.
      All participants will be submitted to a clinical examination and
      electromyographic analysis of the masseter muscles and anterior bundle of the
      temporal muscles bilaterally, to determine TMD. Based on the clinical findings,
      the participants will be classified as having or not having TMD. Those with TMD
      will be divided into four groups, three of which will receive low-level laser
      therapy and one of which will receive a placebo treatment. The treatments will
      involve the TMJ region alone, the masseter and temporal muscles alone, or both
      these regions together. The data will be submitted to descriptive statistical
      analysis. The chi-square test and Fisher's exact test will be used to determine
      associations among the categorical variables. The Student's t test and analysis
      of variance will be used for the comparison of mean electromyographic signals.
      Pearson's correlation coefficients will be calculated for the analysis of
      correlations among the continuous variables. TRIAL REGISTRATION: The protocol for
      this study has been submitted to Clinical Trials - registration number
      NCT01846000.

PMID- 23876096
TI  - Dietary phosphorus and kidney disease.
AB  - High serum phosphate is linked to poor health outcome and mortality in chronic
      kidney disease (CKD) patients before or after the initiation of dialysis.
      Therefore, maintenance of normal serum phosphate levels is a major concern in the
      clinical care of this population with dietary phosphorus restriction and/or use
      of oral phosphate binders considered to be the best corrective care. This review
      discusses (1) evidence for an association between serum phosphate levels and bone
      and cardiovascular disease (CVD) in CKD patients as well as progression of kidney
      disease itself; (2) the relationship between serum phosphate and dietary
      phosphorus intake; and (3) implications from these data for future research.
      Increasing our understanding of the relationship between altered phosphorus
      metabolism and disease in CKD patients may clarify the potential role of excess
      dietary phosphorus as a risk factor for disease in the general population. 

PMID- 23876097
TI  - Dynamic surface site activation: a rate limiting process in electron beam induced
      etching.
AB  - We report a new mechanism that limits the rate of electron beam induced etching
      (EBIE). Typically, the etch rate is assumed to scale directly with the precursor
      adsorbate dissociation rate. Here, we show that this is a special case, and that
      the rate can instead be limited by the concentration of active sites at the
      surface. Novel etch kinetics are expected if surface sites are activated during
      EBIE, and observed experimentally using the electron sensitive material ultra
      nanocrystalline diamond (UNCD). In practice, etch kinetics are of interest
      because they affect resolution, throughput, proximity effects, and the topography
      of nanostructures and nanostructured devices fabricated by EBIE. 

PMID- 23876099
TI  - Limited utility of fluorescence in situ hybridization for common abnormalities of
      myelodysplastic syndrome at first presentation and follow-up of myeloid
      neoplasms.
AB  - Fluorescence in situ hybridization for abnormalities common to myelodysplastic
      syndrome (MDS FISH) is often used with traditional karyotype in the diagnosis and
      monitoring of myeloid neoplasms. However, its value in these roles has been
      questioned. To evaluate its utility, we compared MDS FISH results with karyotype
      in 544 bone marrow specimens obtained for diagnosis (180 cases) or follow-up (364
      cases) of myeloid neoplasia. We found excellent concordance between FISH and
      karyotype, such that FISH is rarely abnormal (1.7% at diagnosis and 3.0% at
      follow-up) in cases with normal karyotype. Even in the rare discordant cases, the
      abnormal FISH has little or no clinical value. Thus, we propose that this test
      should be limited to cases with inadequate karyotype only. Such guidelines could
      result in significant cost savings with no impact on patient diagnosis.

PMID- 23876100
TI  - High dose cytarabine with rituximab is not enough in first-line treatment of
      mantle cell lymphoma with high proliferation: early closure of the Nordic
      Lymphoma Group Mantle Cell Lymphoma 5 trial.

PMID- 23876098
TI  - Efficacy and safety of rituximab plus low-dose oral fludarabine and
      cyclophosphamide as first-line treatment of elderly patients with indolent non
      Hodgkin lymphomas.
AB  - Indolent non-Hodgkin lymphomas (iNHLs) are B-cell neoplasms for which no
      consensus is available about optimal first-line therapy. Chemoimmunotherapy with
      fludarabine, cyclophospamide and rituximab is very effective, but may give severe
      hematological and non-hematological toxicity at standard doses, especially in
      elderly patients. In this phase II study, 25 untreated elderly patients with iNHL
      received rituximab (375 mg/m(2)) plus low-dose oral fludarabine (25 mg/m(2) for 4
      consecutive days) and cyclophosphamide (150 mg/m(2) for 4 consecutive days) for
      four monthly cycles. Twenty-three patients were responsive (92%) and 12 patients
      achieved a complete remission (48%). Twenty-one patients (84%) were alive, median
      follow-up was 30 months and median event-free survival (EFS) was not reached.
      Patients who we previously treated with chemotherapy alone had a shorter EFS
      (median 20 months). Compliance was good, with mild toxicity. This regimen is
      effective for elderly patients with iNHL. The addition of rituximab results in
      long EFS without affecting toxicity.

PMID- 23876101
TI  - Creation and implementation of an emergency medicine education and training
      program in Turkey: an effective educational intervention to address the
      practitioner gap.
AB  - BACKGROUND: The specialty of Emergency Medicine has enjoyed recognition for
      nearly 20 years in Turkey. However, the majority of underserved and rural Turkish
      emergency departments are staffed by general practitioners who lack formal
      training in the specialty and have few opportunities to increase emergency
      medicine-specific knowledge and skills. METHODS: To address this "practitioner
      gap," the authors developed a four-phase comprehensive emergency medicine
      education and training program for general practitioners practicing in government
      hospitals in Turkey. RESULTS: From April 2006 until June 2009, 42 courses were
      taught by 62 trainers across seven regions in Turkey. A total of 2,262 physicians
      were trained. The mean course pre-test score for all regions was 42.3 (95% CI
      39.8 to 44.7). The mean course post-test score was 70.1 (95% CI 67.2 to 72.9).
      The difference between the mean scores was 27.8 (95% CI 25.3 to 30.4, P <0.0001),
      reflecting an improvement of 65.7%. CONCLUSIONS: A partnership between an
      academic emergency medicine department and an emergency medicine society to
      implement country-wide training of physicians practicing in public emergency
      departments can serve as a successful model for capacity-building global
      emergency medicine endeavors.

PMID- 23876102
TI  - Psychosocial factors in people with chronic kidney disease prior to renal
      replacement therapy.
AB  - Increasing evidence implicates psychosocial factors including depression,
      anxiety, perceived social support and health-related quality of life in the
      pathophysiology of various chronic diseases. Research examining the psychosocial
      aspects of kidney disease has focussed predominantly on depressive disorders in
      dialysis patients where they are independently associated with increased risk of
      mortality and poor health-related quality of life. In contrast, studies examining
      the influence of psychosocial factors in people with chronic kidney disease (CKD)
      prior to the initiation of renal replacement therapy are sparse. Limited data
      indicate that clinical depression and depressive symptoms are common and may
      independently predict progression to dialysis, hospitalization and death. In
      contrast, the influence of anxiety disorders, lower perceived social support and
      impaired health-related quality of life on the clinical course of CKD have
      received little attention. Large-scale prospective cohort studies are needed to
      clarify the burden and prognostic impact of these factors in this vulnerable
      population. Given the escalating burden of CKD worldwide examining the role of
      these potentially modifiable risk factors is crucial. Identifying and
      implementing targeted interventions in order to prevent or delay the progression
      of CKD and improve quality of life will be a major challenge. 

PMID- 23876103
TI  - Design for a lithographically patterned bioartificial endocrine pancreas.
AB  - Cell encapsulation provides a means to transplant therapeutic cells for a variety
      of diseases including diabetes. However, due to the large numbers of cells,
      approximately on the order of a billion, that need to be transplanted for human
      diabetes therapy, adequate mass transport of nutrients such as oxygen presents a
      major challenge. Proof-of-concept for the design of a bioartificial endocrine
      pancreas (BAEP) that is optimized to minimize hypoxia in a scalable and precise
      architecture is demonstrated using a combination of simulations and experiments.
      The BAEP is composed of an array of porous, lithographically patterned polyhedral
      capsules arrayed on a rolled-up alginate sheet. All the important structural
      variables such as the capsule dimensions, pore characteristics, and spacing can
      be precisely engineered and tuned. Further, all cells are encapsulated within a
      single device with a volume not much greater than the total volume of the
      encapsulated cells, and no cell within the device is located more than 200 MUm
      from the surrounding medium that facilitates efficient mass transport with the
      surroundings. Compared with gel-based encapsulation methods, our approach offers
      unprecedented precision and tunability of structural parameters as well as the
      volume of the encapsulated cells and consequently the amount of secreted insulin.
      Our work highlights the utility of lithography and self-assembly in the
      fabrication of micro- and nanostructured three-dimensional structures that
      simulate the function of natural endocrine organs.

PMID- 23876104
TI  - Replacement of a quinone by a 5-O-acetylhydroquinone abolishes the accidental
      necrosis inducing effect while preserving the apoptosis-inducing effect of
      renieramycin M on lung cancer cells.
AB  - Renieramycin M (1), a bistetrahydroisoquinolinequinone alkaloid isolated from the
      marine sponge Xestospongia sp., has been reported to possess promising anticancer
      effects. However, its accidental necrosis inducing effect has limited further
      development due to concerns of unwanted toxicity. The presence of two quinone
      moieties in its structure was demonstrated to induce accidental necrosis and
      increase reactive oxygen species (ROS) levels. Therefore, one quinone of 1 was
      modified to produce the 5-O-acetylated hydroquinone derivative (2), and 2
      dramatically reduced the accidental necrosis inducing effect while preserving the
      apoptosis-inducing effect of parent 1 on lung cancer H23 cells. Addition of the
      antioxidant N-acetylcysteine suppressed the accidental necrosis mediated by 1,
      suggesting that its accidental necrosis inducing effect was ROS-dependent. The
      fluorescent probe dihydroethidium revealed that the accidental necrosis mediated
      by 1 was due to its ability to generate intracellular superoxide anions.
      Interestingly, the remaining quinone in 2 was required for its cytotoxicity, as
      the 5,8,15,18-O-tetraacetylated bishydroquinone derivative (3) exhibited weak
      cytotoxicity compared to 1 and 2. The present study demonstrates a simple way to
      eliminate the undesired accidental necrosis inducing effect of substances that
      may be developed as improved anticancer drug candidates. 

PMID- 23876105
TI  - Optimization of a fermented soy product formulation with a kefir culture and
      fiber using a simplex-centroid mixture design.
AB  - The objective of this work was to optimize a fermented soy product formulation
      with kefir and soy, oat and wheat fibers and to evaluate the fiber and product
      characteristics. A simplex-centroid mixture design was used for the optimization.
      Soymilk, soy, oat and wheat fiber mixtures, sucrose and anti-foaming agent were
      used for the formulation, followed by thermal treatment, cooling and the addition
      of flavoring. Fermentation was performed at 25  degrees C with a kefir culture
      until a pH of 4.5 was obtained. The products were cooled, homogenized and stored
      for analysis. From the mathematical models and variables response surface and
      desirability an optimal fermented product was formulated containing 3% (w/w) soy
      fiber. Compared with the other formulations, soy fermented product with 3% soy
      fiber had the best acidity, viscosity, syneresis, firmness and Lactococcus lactis
      count.

PMID- 23876106
TI  - A microfluidic SPLITT device for fractionating low-molecular weight samples.
AB  - In this article, we report the design of a microfluidic split flow thin cell
      (SPLITT) fractionation device with internal electrodes placed across the width of
      its analysis channel for assaying low-molecular weight samples. The reported
      device allows the realization of lateral electric fields and separation distances
      of the orders of 100 V/cm and 500 MUm, respectively, that are suitable for
      fractionating such mixtures with high resolution. Our experiments show that a key
      challenge to realizing electrophoretic fractionations using the current design is
      to minimize the electroosmotically driven fluid circulations in its SPLITT
      channel that tend to hydrodynamically mix the liquid streams flowing through this
      duct. The present work addresses this challenge by chemically modifying the
      surface of our fluidic conduits with a new coating medium, N-(2
      triethoxysilylpropyl) formamide, which has been shown to diminish electroosmotic
      flow in glass microchannels by over 5 orders of magnitude. Finally, we describe
      the integration of the reported microfluidic fractionation device to a mass
      spectrometer via the electrospray ionization interface to allow inline label-free
      detection of analytes in our assay. Product purity greater than 95% has been
      accomplished using the SPLITT system presented here for a sample of peptides
      having the same electrical polarity. 

PMID- 23876107
TI  - Alkali metal directed assembly of heterometallic V(v)/M (M = Na, K, Cs)
      coordination polymers: structures, topological analysis, and oxidation catalytic
      properties.
AB  - The reactions of [VO(acac)2] with bis(salicylaldehyde)-oxaloyldihydrazone (H4L)
      and an alkali metal carbonate M2CO3 (M = K, Na, Cs), in EtOH/H2O medium upon
      reflux, resulted in the generation of three new heterometallic V(V)/M materials,
      namely the 1D [(VO2)2(MU4-L){Na2(MU-H2O)2(H2O)2}]n (1), 2D [{V(MU-O)2}2(MU4
      L){K2(MU-H2O)2(H2O)2}]n (2), and 3D [{V(MU-O)(MU3-O)}2(MU8-L){Cs2(MU
      H2O)2(H2O)2}]n (3) coordination polymers. They were isolated as air-stable solids
      and fully characterized by IR, UV-vis, (1)H, and (51)V NMR spectroscopy, ESI
      MS(+/-), elemental, thermal, and single-crystal X-ray diffraction analyses, the
      latter showing that 1-3 are constructed from the resembling [(VO2)2(MU(4/8)-L)](2
      ) blocks assembled by the differently bound aqua-metal [M2(MU-H2O)2(H2O)2](2+)
      moieties (M = Na, K, Cs). The main distinctive features of 1-3 arise from the
      different coordination numbers of Na (5), K (7), and Cs (9) atoms, thus
      increasing the complexity of the resulting networks from the ladder-like 1D
      chains in 1 to double 2D layers in 2, and layer-pillared 3D framework in 3. The
      topological analysis of 2 disclosed a uninodal 4-connected underlying net with a
      rare kgm [Shubnikov plane net (3.6.3.6)/kagome pattern] topology, while 3
      features a trinodal 4,7,8-connected underlying net with an unprecedented
      topology. Compounds 1-3 also show solubility in water (S(25  degrees C) ~ 4-7 mg
      mL(-1)) and were applied as efficient precatalysts for the homogeneous oxidation
      of cyclohexane by aqueous H2O2, under mild conditions (50  degrees C) in MeCN/H2O
      medium and in the presence of an acid promoter. Total yields (based on substrate)
      of cyclohexanol and cyclohexanone up to 36% and turnover numbers (TONs) up to
      5700 were achieved.

PMID- 23876108
TI  - Three legacies of humanitarianism in China.
AB  - The rise of China has altered the context of the international humanitarian
      community of donors and aid agencies. China is becoming one of the key actors in
      this grouping, undertaking infrastructure projects in areas in which paramount
      humanitarian challenges exist. The literature discusses how the Chinese approach
      differs from that of Western donors, but it does not pay much attention to why
      China concentrates on its state-centric and infrastructure-based approach. This
      paper seeks to shed some light on this subject by examining the historical
      evolution of the concept of humanitarianism in China. This evolution has produced
      three legacies: (i) the ideal of a well-ordered state; (ii) anti-Western
      sentiment; and (iii) the notion of comprehensive development based on a human
      oriented approach. China's policies and discourses on assistance in humanitarian
      crises today rest on these three legacies. Traditional donors would be well
      advised to consider carefully the implications of the Chinese understanding of
      humanitarianism when engaging with the country. 

PMID- 23876109
TI  - Near-infrared absorbing Cu12Sb4S13 and Cu3SbS4 nanocrystals: synthesis,
      characterization, and photoelectrochemistry.
AB  - Herein, we present the novel synthesis of tetrahedrite copper antimony sulfide
      (CAS) nanocrystals (Cu12Sb4S13), which display strong absorptions in the visible
      and NIR. Through ligand tuning, the size of the Cu12Sb4S13 NCs may be increased
      from 6 to 18 nm. Phase purity is achieved through optimizing the ligand chemistry
      and maximizing the reactivity of the antimony precursor. We provide a detailed
      investigation of the optical and photoelectrical properties of both tetrahedrite
      (Cu12Sb4S13) and famatinite (Cu3SbS4) NCs. These NCs were found to have very high
      absorption coefficients reaching 10(5) cm(-1) and band gaps of 1.7 and 1 eV for
      tetrahedrite and famatinite NCs, respectively. Ultraviolet photoelectron
      spectroscopy was employed to determine the band positions. In each case, the
      Fermi energies reside close to the valence band, indicative of a p-type
      semiconductor. Annealing of tetrahedrite CAS NC films in sulfur vapor at 350 
      degrees C was found to result in pure famatinite NC films, opening the
      possibility to tune the crystal structure within thin films of these NCs.
      Photoelectrochemistry of hydrazine free unannealed films displays a strong p-type
      photoresponse, with up to 0.1 mA/cm(2) measured under mild illumination.
      Collectively these optical properties make CAS NCs an excellent new candidate for
      both thin film and hybrid solar cells and as strong NIR absorbers in general. 

PMID- 23876111
TI  - Number of women requiring care at a tertiary hospital equipped with a neonatal
      intensive care unit at night in an area with a population of 2 million.
AB  - AIM: Women with imminent premature labor (IPL) are transported to a tertiary
      hospital equipped with neonatal intensive care unit (NICU) even during the night.
      However, there have been no extensive studies of the occurrence rate of night
      IPL. The aim of this study was to determine the occurrence rate of night IPL in
      an area with a population of 2 million. MATERIALS AND METHODS: A retrospective
      analysis was conducted using data collected by the Sapporo Obstetric System for
      Emergency Patients launched in October 2008, in which women, physicians, and
      ambulance staff who sought appropriate obstetric/gynecological facilities
      available in the night (19.00-06.00 hours) were informed of candidate hospitals
      by coordinators through telephone consultation. This system covered the Sapporo
      area, which has a population of 2,000,000 and 17,000 births annually.
      Approximately 14% and 86% of women received antenatal care at six and 35
      obstetric facilities with and without NICU, respectively, in this area. Night IPL
      was defined as a threatened premature labor and transport to one of six tertiary
      hospitals with NICU between 19.00 and 06.00 hours the next morning. RESULTS:
      During a 4-year period from 1 October 2008 to 30 September 2012, the Sapporo
      Obstetric System for Emergency Patients received 158 +/- 23 (mean +/- standard
      deviation) monthly telephone consultations (range 114-218 per month). The monthly
      number of patients with night IPL was 3.0 +/- 2.2 (range 0-9 per month).
      CONCLUSIONS: The monthly number of cases of night IPL was around three among
      women who received antenatal care at obstetrics facilities without NICU in an
      area with a population of 2,000,000.

PMID- 23876110
TI  - The circadian clock is functional in eosinophils and mast cells.
AB  - Allergic diseases are frequently exacerbated between midnight and early morning,
      suggesting a role for the biological clock. Mast cells (MC) and eosinophils are
      the main effector cells of allergic diseases and some MC-specific or eosinophil
      specific markers, such as tryptase or eosinophil cationic protein, exhibit
      circadian variation. Here, we analysed whether the circadian clock is functional
      in mouse and human eosinophils and MC. Mouse jejunal MC and polymorphonuclear
      cells from peripheral blood (PMNC) were isolated around the circadian cycle.
      Human eosinophils were purified from peripheral blood of non-allergic and
      allergic subjects. Human MC were purified from intestinal tissue. We found a
      rhythmic expression of the clock genes mPer1, mPer2, mClock and mBmal1 and
      eosinophil-specific genes mEcp, mEpo and mMbp in murine PMNC. We also found
      circadian variations for hPer1, hPer2, hBmal1, hClock, hEdn and hEcp mRNA and
      eosinophil cationic protein (ECP) in human eosinophils of both healthy and
      allergic people. Clock genes mPer1, mPer2, mClock and mBmal1 and MC-specific
      genes mMcpt-5, mMcpt-7, mc-kit and mFcepsilonRI alpha-chain and protein levels of
      mMCPT5 and mc-Kit showed robust oscillation in mouse jejunum. Human intestinal MC
      expressed hPer1, hPer2 and hBmal1 as well as hTryptase and hFcepsilonRI alpha
      chain, in a circadian manner. We found that pre-stored histamine and de novo
      synthesized cysteinyl leukotrienes, were released in a circadian manner by MC
      following IgE-mediated activation. In summary, the biological clock controls MC
      and eosinophils leading to circadian expression and release of their mediators
      and, hence it might be involved in the pathophysiology of allergy. 

PMID- 23876112
TI  - "Even if the test result is negative, they should be able to tell us what is
      wrong with us": a qualitative study of patient expectations of rapid diagnostic
      tests for malaria.
AB  - BACKGROUND: The debate on rapid diagnostic tests (RDTs) for malaria has begun to
      shift from whether RDTs should be used, to how and under what circumstances their
      use can be optimized. This has increased the need for a better understanding of
      the complexities surrounding the role of RDTs in appropriate treatment of fever.
      Studies have focused on clinician practices, but few have sought to understand
      patient perspectives, beyond notions of acceptability. METHODS: This qualitative
      study aimed to explore patient and caregiver perceptions and experiences of RDTs
      following a trial to assess the introduction of the tests into routine clinical
      care at four health facilities in one district in Ghana. Six focus group
      discussions and one in-depth interview were carried out with those who had
      received an RDT with a negative test result. RESULTS: Patients had high
      expectations of RDTs. They welcomed the tests as aiding clinical diagnoses and as
      tools that could communicate their problem better than they could, verbally.
      However, respondents also believed the tests could identify any cause of illness,
      beyond malaria. Experiences of patients suggested that RDTs were adopted into an
      existing system where patients are both physically and intellectually removed
      from diagnostic processes and where clinicians retain authority that supersedes
      tests and their results. In this situation, patients did not feel able to
      articulate a demand for test-driven diagnosis. CONCLUSIONS: Improvements in
      communication between the health worker and patient, particularly to explain the
      capabilities of the test and management of RDT negative cases, may both manage
      patient expectations and promote patient demand for test-driven diagnoses.

PMID- 23876113
TI  - Age and apolipoprotein E genotype influence rate of cognitive decline in
      nondemented elderly.
AB  - OBJECTIVE: This study examined the impact of age and apolipoprotein E (APOE)
      genotype on the rate of cognitive decline in nondemented elderly participants in
      a simulated Alzheimer's disease (AD) primary prevention treatment trial carried
      out by the Alzheimer's Disease Cooperative Study. METHOD: Cognitive tests were
      administered at baseline and at four subsequent annual evaluations to 417
      nondemented participants (172 men, 245 women) between the ages of 74 and 93 (M =
      79.13 +/- 3.34). APOE genotyping was available for 286 of the participants.
      RESULTS: Four-year decline was evident on measures of orientation, memory,
      executive function, and language. Faster decline was evident in APOE epsilon4+ (a
      genetic risk factor for AD; n = 73) than in epsilon4- participants (n = 213),
      even after controlling for education, gender, ethnicity, and baseline functional
      and cognitive abilities. This discrepancy increased with age, indicating an Age *
      Genotype interaction. CONCLUSION: These results are consistent with population
      based studies, and extend the findings to a carefully screened sample that meets
      inclusion and exclusion criteria for an AD primary prevention trial. The
      interaction between age and APOE genotype on rate of decline suggests that
      preclinical disease may be overrepresented in older epsilon4+ individuals. Thus,
      APOE genotype and age should be considered in the design of AD primary prevention
      treatment trials.

PMID- 23876114
TI  - Nonlinear correlations impair quantification of episodic memory by mesial
      temporal BOLD activity.
AB  - OBJECTIVE: Episodic memory processes can be investigated using different
      functional MRI (fMRI) paradigms. The purpose of the present study was to examine
      correlations between neuropsychological memory test scores and BOLD signal
      changes during fMRI scanning using three different memory tasks. METHOD: Twenty
      eight right-handed healthy subjects underwent three paradigms, (a) a word pair,
      (b) a space-labyrinth, and (c) a face-name association paradigm. These paradigms
      were compared for their value in memory quantification and lateralization by
      calculating correlations between the BOLD signals in the mesial temporal lobe and
      behavioral data derived from a neuropsychological test battery. RESULTS: As
      expected, group analysis showed left-sided activation for the verbal, a tendency
      to right-sided activation for the spatial, and bilateral activation for the face
      name paradigm. No linear correlations were observed between neuropsychological
      data and activation in the temporo-mesial region. However, we found significant u
      shaped correlations between behavioral memory performance and activation in both
      the verbal and the face-name paradigms, that is, BOLD signal changes were greater
      not only among participants who performed best on the neuropsychological tests,
      but also among the poorest performers. The figural learning task did not
      correlate with the activations in the space-labyrinth paradigm at all.
      CONCLUSIONS: We interpreted the u-shaped correlations to be due to compensatory
      hippocampal activations associated with low performance when people try
      unsuccessfully to remember presented items. Because activation levels did not
      linearly increase with memory performance, the latter cannot be quantified by
      fMRI alone, but only be used in conjunction with neuropsychological testing.

PMID- 23876116
TI  - Directional and spatial motor intentional disorders in patients with right versus
      left hemisphere strokes.
AB  - OBJECTIVE: Motor intentional disorders (MIDs) are characterized by dysfunction in
      the preparation, initiation, maintenance, and termination of goal-oriented
      actions. In this study, we investigated (1) whether patients with right
      hemisphere strokes (RHS) and left hemisphere strokes (LHS) differ in the
      frequency of delayed action initiation (hypokinesia) and motor impersistence; (2)
      whether there is a directional or hemispatial component of hypokinesia or motor
      impersistence; (3) whether there is an association between the presence of
      hemispatial neglect and tests for MID; and (4) the location of injury associated
      with MID. METHOD: Thirty-two patients with acute unilateral stroke (21 with RHS
      and 11 with LHS) and 12 age-matched healthy controls participated in the study.
      To determine the presence and severity of directional and spatial hypokinesia and
      impersistence we used a new apparatus, the Directional Movement Tester (DMT).
      While being tested with the DMT, the participants held a static bar located
      either in the right or left hemispace using either their right or left hand and
      upon stimulus onset pushed the bar either leftward or rightward and maintained a
      given force for 10 sec. RESULTS AND CONCLUSION: The frequency of hypokinesia and
      impersistence was higher in the RHS group than in the LHS group, but there were
      no hypokinetic directional or spatial asymmetries. The RHS group did demonstrate
      left contralesional directional impersistence, but there were no spatial
      asymmetries of impersistence. Signs of hemispatial neglect were not associated
      with these measures of MID. Participants with frontal or subcortical lesions were
      significantly more likely to demonstrate hypokinesia and impersistence than those
      with posterior lesions.

PMID- 23876117
TI  - Heterogeneity of brain lesions in pediatric traumatic brain injury.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) provides a method to identify and
      quantify abnormalities resulting from traumatic brain injury (TBI). MRI
      abnormalities in children with TBI have not been fully characterized according to
      the frequency, location, and quantitative measurement of a range of pathologies
      critical for studies of neuropsychological outcome. Here, we report MRI findings
      from a large, multicenter study of childhood TBI, the Social Outcomes of Brain
      Injury in Kids (SOBIK) study, which compared qualitative and quantitative
      neuroimaging findings in 72 children with complicated mild-to-severe TBI to 52
      children with orthopedic injury (OI). METHOD: Qualitative analyses of MRI scans
      coded white matter hyperintensities (WMHs), hemosiderin deposits reflecting prior
      hemorrhagic lesions, regions of encephalomalacia and/or atrophy, and corpus
      callosum atrophy and traumatic shear lesions. Two automated quantitative analyses
      were conducted: (a) FreeSurfer methods computed volumes for total brain, white
      matter (WM), gray matter (GM), corpus callosum, ventricles, amygdala,
      hippocampus, basal ganglia, and thalamus along with a ventricle-to-brain ratio
      (VBR); and (b) voxel-based morphometry (VBM) to identify WM, GM, and
      cerebrospinal fluid. We also examined performance on the Processing Speed Index
      (PSI) from the Wechsler Intelligence Scale for Children, Fourth Edition, in
      relation to the above-mentioned neuroimaging variables. RESULTS: WMHs,
      hemosiderin deposits, and focal areas of encephalomalacia or atrophy were common
      in children with TBI, were related to injury severity, and were mostly observed
      within a frontotemporal distribution. Quantitative analyses showed volumetric
      changes related to injury severity, especially ventricular enlargement and
      reduced corpus callosum volume. VBM demonstrated similar findings, but, in
      addition, GM reductions in the inferior frontal, basal forebrain region,
      especially in the severe TBI group. The complicated mild TBI group showed few
      differences from the OI group. PSI was significantly associated with global
      atrophy, as measured by VBR. CONCLUSION: MRI findings after childhood TBI are
      diverse and particularly influenced by injury severity, and they involve common
      features, group heterogeneity, and individual variability.

PMID- 23876115
TI  - Child maltreatment and executive functioning in middle adulthood: a prospective
      examination.
AB  - OBJECTIVE: There is extensive evidence of negative consequences of childhood
      maltreatment for IQ, academic achievement, and posttraumatic stress disorder
      (PTSD), and increased attention to neurobiological consequences. However, few
      prospective studies have assessed the long-term effects of abuse and neglect on
      executive functioning. This study examined whether childhood abuse and neglect
      predicts components of executive functioning and nonverbal reasoning ability in
      middle adulthood and whether PTSD moderates this relationship. METHOD: Using a
      prospective cohort design, a large sample (N = 792) of court-substantiated cases
      of childhood physical and sexual abuse and neglect (ages 0-11 years) and matched
      controls were followed into adulthood (mean age = 41 years). Executive
      functioning was assessed with the Trail Making Test-Part B and nonverbal
      reasoning was assessed with the Matrix Reasoning test. PTSD (DSM-III-R lifetime
      diagnosis) was assessed at age 29 years. Data were analyzed using ordinary least
      squares regressions, controlling for age, sex, and race, and possible confounds
      of IQ, depression, and excessive alcohol use. RESULTS: In multivariate analyses,
      childhood maltreatment overall and childhood neglect predicted poorer executive
      functioning and nonverbal reasoning at age 41 years, whereas physical and sexual
      abuse did not. A past history of PTSD did not mediate or moderate these
      relations. CONCLUSIONS: Childhood maltreatment and neglect specifically have a
      significant long-term impact on important aspects of adult neuropsychological
      functioning. These findings suggest the need for targeted efforts dedicated to
      interventions for neglected children.

PMID- 23876118
TI  - Metacognitive monitoring and dementia: how intrinsic and extrinsic cues influence
      judgments of learning in people with early-stage Alzheimer's disease.
AB  - OBJECTIVE: The present research compared metamemorial monitoring processes among
      younger adults, nondemented older adults, and older adults diagnosed with early
      stage Dementia of the Alzheimer's Type (DAT). METHOD: In three experiments we
      examined the influence of intrinsic and extrinsic cues on Judgment of Learning
      (JOL) accuracy. Changes in association strength between cue-target word pairs
      served as the intrinsic manipulation in Experiments 1 and 2. Changes in encoding
      orientation served as the extrinsic manipulation in Experiment 3. RESULTS: Across
      all experiments we found that young adults, nondemented older adults, and
      individuals in the early stages of DAT effectively used intrinsic and extrinsic
      factors to guide JOL predictions. CONCLUSIONS: We conclude that while certain
      aspects of metacognition may be impaired in both the normal and demented older
      populations, these groups remain able to use theory-based processing, or general
      knowledge about how memory works, to make metamemory monitoring predictions.

PMID- 23876119
TI  - Interhemispheric coupling improves the brain's ability to perform low cognitive
      demand tasks in Alzheimer's disease and high cognitive demand tasks in normal
      aging.
AB  - OBJECTIVE: Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      that affects the corpus callosum (CC), which plays a key role in interhemispheric
      coupling in high-demand conditions. Using 3D callosal measurements and a letter
      matching paradigm, this 2-part study investigated the neural substrate of
      interhemispheric coupling in individuals with AD or amnestic mild cognitive
      impairment (a-MCI) and age-matched healthy individuals (HC). METHOD: Thirty-three
      right-handed participants were MRI scanned to measure the volume of the CC in 5
      sections. In Study 1, AD, a-MCI, and HC individuals performed a low-demand
      perceptual letter shape-matching task (e.g., A-A); in Study 2, a-MCI and HC
      individuals performed a "case-sensitive" letter-matching task (Study 2A) and a
      "load-sensitive" letter-matching task (Study 2B). RESULTS: The results showed a
      positive correlation between Response Times and the midbody of the CC at the
      lowest cognitive demand level (Study 1) in participants with AD, and the total
      CC, midbody, caudal body, and isthmus of the CC at high cognitive demand levels
      (Study 2A) in normal aging. The volume of the anterior part of the CC was
      significantly negatively correlated with the interhemispheric behavioral indices
      for the a-MCI group (Study 1 and Study 2B). CONCLUSION: This study provides
      evidence that interhemispheric coupling may constitute a flexible mechanism that
      can improve the brain's ability to meet processing demands for low cognitive
      demand in AD and for high cognitive demand in normal aging.

PMID- 23876120
TI  - Intraindividual cognitive variability before and after sports-related concussion.
AB  - OBJECTIVE: Inconsistent performance is associated with cognitive dysfunction in a
      number of clinical populations. However, intraindividual cognitive variability in
      healthy individuals is poorly understood. Inconsistency poses a challenge to
      clinicians when interpreting change over time. This study examined
      intraindividual cognitive variability within a sample of college athletes tested
      at baseline and postconcussion. METHOD: Athletes (n = 71) and control
      participants (n = 42) were tested with a comprehensive neuropsychological battery
      at baseline and postconcussion (athletes) or one month later (controls). A subset
      of indices with high internal consistency was used to calculate overall
      performance and performance variability. A k-means cluster analysis of baseline
      and postconcussion performance variability examined heterogeneity within the
      sample. RESULTS: In the athlete sample, performance variability was significantly
      greater than zero, and was negatively correlated with overall performance at both
      time points (p < .001). Wechsler Test of Adult Reading Full Scale IQ estimate was
      significantly correlated with overall performance (p < .01), but not with
      performance variability. Cluster analysis revealed low-variability (n = 46) and
      high-variability (n = 25) cluster groups. Whereas the low-variability cluster
      group exhibited a pattern of performance similar to that of control participants,
      membership in the high-variability cluster group was associated with
      postconcussion cognitive dysfunction. CONCLUSION: These findings suggest that
      normative cognitive performance in college athletes is characterized by
      significant intraindividual variation across tests. Cross-test intraindividual
      variability may impart clinically meaningful information, as higher levels of
      variability were related to poorer overall performance and postconcussion
      cognitive dysfunction.

PMID- 23876121
TI  - Neuropsychology of decision making and psychopathy in high-risk ex-offenders.
AB  - OBJECTIVE: We examined the relationship of socially maladaptive behaviors with
      decision making and psychopathy in a sample of 26 high-risk males recently
      released from incarceration who were currently clients in an offender reentry
      service program. METHOD: The Iowa Gambling Task (IGT) and the Psychopathy
      Checklist Revised (PCL-R) provided measures of individual differences in decision
      making and psychopathy, respectively. RESULTS: The IGT and PCL-R each contributed
      differentially to specific socially disadvantageous outcomes, with poorer
      decision-making scores predicting recidivism at 3- to 6-month follow-up, and
      higher psychopathy linked to a retrospective measure of total lifetime
      incarceration. In addition, in relation to both nonrecidivist and control groups,
      recidivists showed a distinct pattern of IGT performance for the last 3 blocks of
      trials, characterized by a failure to learn from feedback and to modify their
      preferences to more advantageous decks of cards. In addition, the IGT and PCL-R
      correlated, with poorer decision making corresponding to higher ratings in
      psychopathy. CONCLUSIONS: The current findings may add to growing evidence of
      ecological validity of both decision making and psychopathy in relation to real
      life outcome measures in high-risk individuals.

PMID- 23876122
TI  - Factors underlying probabilistic and deterministic stimulus-response learning
      performance in medicated and unmedicated patients with Parkinson's disease.
AB  - OBJECTIVE: Prior studies have not tested individual differences or effects of
      medication dosage on stimulus-response learning in patients with Parkinson's
      disease (PD). In the current study, we investigated the effects of motor
      variables (including tremor, akinesia, and disease duration) as well as
      dopaminergic medication dosage on learning in unmedicated PD patients, medicated
      PD patients, and healthy controls. METHOD: We tested all subjects on
      probabilistic and deterministic learning tasks, and also collected awareness
      measures data using postexperimental questionnaires. Importantly, we tested
      learning performance in tremor-dominant and akinesia-dominant PD patients, and
      further correlated learning performance with disease duration and medication
      dosage. RESULTS: Results show that akinesia-dominant patients were more impaired
      than tremor-dominant patients at probabilistic reward- but not punishment-based
      learning, which is in agreement with prior studies of the relationship between
      akinesia and basal ganglia dysfunction. We also found no difference between
      medicated and unmedicated PD patients in reward- or punishment-based
      deterministic learning, but medicated patients were better than unmedicated
      patients at reward-based probabilistic learning. Our results show that awareness
      measures explain differences among probabilistic and deterministic learning
      performance. Moreover, we found that disease duration and motor severity are
      inversely correlated, and medication dosage is positively correlated, with reward
      based probabilistic learning. CONCLUSION: Our results suggest that stimulus
      response learning performance in patients with PD depends on the type of learning
      (probabilistic vs. deterministic), medication status (on vs. off medication,
      dopaminergic medication dosage), disease duration as well as motor severity and
      subtype in PD patients (tremor- vs. akinesia-dominant).

PMID- 23876123
TI  - Fasting glucose level is associated with nocturnal hypoglycemia in elderly male
      patients with type 2 diabetes.
AB  - BACKGROUND: Nocturnal hypoglycemia was a common and serious problem among
      patients with type 2 diabetes (T2DM), especially in the elderly. This study
      investigated whether fasting glucose was an indicator of nocturnal hypoglycemia
      in elderly male patients with T2DM. METHODS: A total of 291 elderly male type 2
      diabetic patients who received continuous glucose monitoring (CGM) between
      January 2007 and January 2011 were enrolled in the study. The association of
      fasting glucose and nocturnal hypoglycemia based on CGM data was analyzed,
      comparing with bedtime glucose. RESULTS: Based on CGM data, patients with
      nocturnal hypoglycemia had significantly lower fasting glucose (5.88 +/- 1.29
      versus 6.92 +/- 1.32 mmol/L) and bedtime glucose (7.33 +/- 1.70 versus 8.01 +/-
      1.95 mmol/L) than patients without nocturnal hypoglycemia (both p < 0.01).
      Compared with the highest quartile, the lowest quartile of fasting glucose had a
      significantly increased risk of nocturnal hypoglycemia after the multiple
      adjustments (pfor trend < 0.001). However, this association did not appear in
      bedtime glucose. When the prediction of nocturnal hypoglycemia either by fasting
      glucose or bedtime glucose using the area under receiver operating characteristic
      (ROC) curve, fasting glucose but not bedtime glucose, was an indicator of
      nocturnal hypoglycemia, with an area under the ROC curve (AUC) of 0.714 (95% CI:
      0.653 ~ 0.774, p < 0.001). On the ROC curve, the Youden index was maximal when
      fasting glucose was 6.1 mmol/L. CONCLUSIONS: Fasting glucose may be a convenient
      and clinically useful indicator of nocturnal hypoglycemia in elderly male
      patients with T2DM. Risk of nocturnal hypoglycemia significantly increased when
      fasting glucose was less than 6.1 mmol/L.

PMID- 23876125
TI  - Enhanced stability of low fouling zwitterionic polymer brushes in seawater with
      diblock architecture.
AB  - The successful implementation of zwitterionic polymeric brushes as antifouling
      materials for marine applications is conditioned by the stability of the polymer
      chain and the brush-anchoring segment in seawater. Here we demonstrate that
      robust, antifouling, hydrophilic polysulfobetaine-based brushes with diblock
      architecture can be fabricated by atom-transfer radical polymerization (ATRP)
      using initiator-modified surfaces. Sequential living-type polymerization of
      hydrophobic styrene or methyl methacrylate and commercially available hydrophilic
      sulfobetaine methacrylamide (SBMAm) monomer is employed. Stability enhancement is
      accomplished by protecting the siloxane anchoring bond of brushes on the
      substrate, grafted from silicon oxide surfaces. The degradation of unprotected
      PSBMAm brushes is clearly evident after a 3 month immersion challenge in
      sterilized artificial seawater. Ellipsometry and atomic force microscopy (AFM)
      measurements are used to follow changes in coating thickness and surface
      morphology. Comparative stability results indicate that surface-tethered
      poly(methyl methacrylate) and polystyrene hydrophobic blocks substantially
      improve the stability of zwitterionic brushes in an artificial marine
      environment. In addition, differences between the hydration of zwitterionic
      brushes in fresh and salt water are discussed to provide a better understanding
      of hydration and degradation processes with the benefit of improved design of
      polyzwitterionic coatings. 

PMID- 23876124
TI  - Phenotypic characterisation of the cellular immune infiltrate in placentas of
      cattle following experimental inoculation with Neospora caninum in late
      gestation.
AB  - Despite Neospora caninum being a major cause of bovine abortion worldwide, its
      pathogenesis is not completely understood. Neospora infection stimulates host
      cell-mediated immune responses, which may be responsible for the placental damage
      leading to abortion. The aim of the current study was to characterize the
      placental immune response following an experimental inoculation of pregnant
      cattle with N. caninum tachyzoites at day 210 of gestation. Cows were culled at
      14, 28, 42 and 56 days post inoculation (dpi). Placentomes were examined by
      immunohistochemistry using antibodies against macrophages, T-cell subsets (CD4,
      CD8 and gammadelta), NK cells and B cells. Macrophages were detected mainly at 14
      days post inoculation. Inflammation was generally mild and mainly characterized
      by CD3+, CD4+ and gammadelta T-cells; whereas CD8+ and NK cells were less
      numerous. The immune cell repertoire observed in this study was similar to those
      seen in pregnant cattle challenged with N. caninum at early gestation. However,
      cellular infiltrates were less severe than those seen during first trimester
      Neospora infections. This may explain the milder clinical outcome observed when
      animals are infected late in gestation.

PMID- 23876126
TI  - The use of the head louse as a remedy for jaundice in Spanish folk medicine: an
      overview.
AB  - BACKGROUND: In Spain, head lice are considered a therapeutic resource for the
      treatment of jaundice. All folk remedies based on the ingestion of these insects
      meet in the present document, previously dispersed among a large number of
      references. METHODS: An overview of the Spanish literature has been carried out.
      The most important databases have been consulted. All related works have been
      examined. RESULTS: Although the method of preparation is diverse and the dose
      varies, the primary recommendation is a transference ritual consisting of taking
      nine live lice for nine days on an empty stomach without the patient's knowledge.
      This traditional knowledge survives in Spanish society, and constitutes an
      example of the interrelation between Spanish and Latin American folk medicines.
      CONCLUSIONS: The survival of this therapy in the worldview of certain rural
      communities suggests the need to take into account the beliefs, ideas and
      behaviour patterns of popular culture in relation to health and disease.

PMID- 23876127
TI  - Nurses and subordination: a historical study of mental nurses' perceptions on
      administering aversion therapy for 'sexual deviations'.
AB  - This study aimed to examine the meanings that nurses attached to the 'treatments'
      administered to cure 'sexual deviation' (SD) in the UK, 1935-1974. In the UK,
      homosexuality was considered a classifiable mental illness that could be 'cured'
      until 1992. Nurses were involved in administering painful and distressing
      treatments. The study is based on oral history interviews with fifteen nurses who
      had administered treatments to cure individuals of their SD. The interviews were
      transcribed for historical interpretation. Some nurses believed that their role
      was to passively follow any orders they had been given. Other nurses limited
      their culpability concerning administering these treatments by adopting
      dehumanising and objectifying language and by focussing on administrative tasks,
      rather than the human beings in need of their care. Meanwhile, some nurses
      genuinely believed that they were acting beneficently by administering these
      distinctly unpleasant treatments. It is envisaged that this study might act to
      reiterate the need for nurses to ensure their interventions have a sound evidence
      base and that they constantly reflect on the moral and value base of their
      practice and the influence that science and societal norms can have on changing
      views of what is considered 'acceptable practice'. 

PMID- 23876128
TI  - 'Safe enough in here?': patients' expectations and experiences of feeling safe in
      an acute psychiatric inpatient ward.
AB  - AIMS AND OBJECTIVES: To understand the experience of being a patient on an acute
      psychiatric inpatient ward. BACKGROUND: Acute psychiatric inpatient care is an
      integral part of the mental health system. A key driver for admission to acute
      wards is risk. Previous research indicates that people do not always feel safe
      when in an acute ward. Understanding the patient experience of safety can
      influence nursing practice, as well as policy and service development. DESIGN: A
      qualitative approach was used. Patient experience was conceptualised as
      represented through narrative as data. Sociolinguistic theories linking narrative
      structure with meaning informed the development of the analytic framework.
      METHODS: Thirteen patients with a variety of diagnoses were recruited from an
      acute ward. Unstructured interviews were carried out in participants' homes two
      and six weeks postdischarge. Holistic analysis of each individual's data set was
      undertaken. Themes running across these holistic analyses were then identified
      and developed. RESULTS: Participant narratives were focused around themes of
      help, safety and power. This study presents findings relating to the experience
      of safety. Participants expected to be safe from themselves and from others.
      Initially, they experienced a sense of safety from the outside world. Lack of
      knowledge of their fellow patients made them feel vulnerable. Participants
      expected the nurses to keep them safe, and felt safer when there were male nurses
      present. CONCLUSIONS: Participants talk about safety in terms of psychological
      and physical safety. A key issue was the perception of threat from other
      patients, highlighting the need to consider patient safety as more than physical
      safety. RELEVANCE TO PRACTICE: Nurses need to be sensitive to the possibility
      that patients feel unsafe in the absence of obvious threat. Institutional
      structures that challenge patients' sense of safety must be examined.

PMID- 23876129
TI  - Case report: concurrent herpesviral and presumptive iridoviral infection
      associated with disease in cultured shortnose sturgeon, Acipenser brevirostrum
      (L.), from the Atlantic coast of Canada.
AB  - Approximately 8 weeks after a chlorine insult associated with the city water
      supply, shortnose sturgeon, Acipenser brevirostrum (L.), from one group presented
      with small (3-4 mm) irregular foci of cutaneous pallor that involved the
      dorsocranial integument with progressive ulceration of the nascent lesions.
      Various bacterial organisms were isolated from the cutaneous lesions, but not
      from the internal viscera. Histologically, the nuclei of the intralesional and
      perilesional epidermal cells often exhibited margination of the chromatin that
      resulted in a homogenous, pale, amphophilic, tinctorial quality of the
      nucleoplasm consistent with a herpesvirus infection. In addition, rare lamellar
      epithelial cells were prominently enlarged due to an abundant, dense, basophilic
      cytoplasm characteristic of an iridovirus infection. Inoculation of cutaneous
      lesion and kidney, spleen, liver sample pools from affected shortnose sturgeon
      onto white sturgeon spleen (WSS-2) cell line induced cytopathic effect
      characterized by syncytia formation. Ultrastructural analysis of infected WSS-2
      cells revealed viral particles with a characteristic herpesvirus morphology.
      Intranuclear hexagonal capsids had a diameter of 95-108 nm, and enveloped
      particles present in the cytoplasm of infected cells had a diameter of 176-196
      nm. This is the first report of a herpesvirus and a possible iridovirus-like
      infection in shortnose sturgeon.

PMID- 23876130
TI  - Current strategies for the treatment of complicated intraabdominal infections.
AB  - INTRODUCTION: Complicated intraabdominal infections (cIAIs) are a common cause of
      infection-related morbidity and mortality in hospitalized patients and present
      many challenges unique from other serious infections. cIAIs are generally
      polymicrobial in nature; however, controversy exists around the pathogenicity of
      some of the frequently identified microorganisms. Increasing antibiotic
      resistance among commonly isolated bacteria poses further challenges for
      clinicians managing patients with cIAIs. AREAS COVERED: This article highlights
      the microbiology and recent trends in antibiotic resistance most relevant to
      cIAIs, provides recommendations for treatment using currently available
      antimicrobials and introduces antibiotics in development with potential roles in
      managing cIAIs. EXPERT OPINION: Successful treatment of cIAI requires a
      combination of timely source control and thorough assessment of patient
      characteristics to guide selection of an appropriate empiric antimicrobial
      regimen. Specific considerations that should be made when choosing antibiotics
      include the origin of infection, presence of risk factors for potentially
      resistant pathogens and severity of disease. While it is encouraging that agents
      in development may prove helpful in the treatment of cIAIs with resistant
      pathogens, further identification of novel antibiotics is needed to address this
      growing concern. In addition, adherence to the principles of antimicrobial
      stewardship is needed if current antimicrobial resources are to be preserved for
      the treatment of cIAIs.

PMID- 23876132
TI  - Improved retinal ganglion cell survival through retinal microglia suppression by
      a chinese herb extract, triptolide, in the DBA/2J mouse model of glaucoma.
AB  - To investigate the changes in retinal microglia and retinal ganglion cell (RGC)
      survival after long-term administration of a Chinese herb extract, triptolide, in
      a DBA/2J mice. DBA/2J mice (n = 96) were administered triptolide (n = 48) 25
      ug/kg or vehicle (n = 48) and were judged at 7, 9, 11 months of age. Long-term
      triptolide treatment tended to attenuate the anterior segment pathology in
      experimental group, though intraocular pressure was not significantly different
      between the two groups. In the experimental group, RGC survival was improved (7,
      9, 11 months: p = 0.035, 0.004, 0.014), and microglia activation was suppressed
      based on a more ramified appearance (9, 11 months: p = 0.024, 0.013) and a lower
      total microglial cell count (7, 9, 11 months: p = 0.028, 0.025, 0.014). Double
      immunofluorescence staining revealed TNF? localized to microglia, TNFR1 localized
      to the RGCs and nerve fiber layer. These findings indicate that long-term
      triptolide administration suppressed microglia activation and improved RGC
      survival in DBA/2J mice.

PMID- 23876133
TI  - Tandem Michael addition/cyclization reaction of 2,3-allenoates with organozincs:
      facile synthesis of isocoumarins.
AB  - A series of isocoumarin derivatives have been synthesized via the reaction of 2
      (o-(methoxycarbonyl)phenyl)-2,3-allenoates with organozincs in CH2Cl2 at room
      temperature (for dialkylzinc) or 100  degrees C (for Ph2Zn) through a tandem
      Michael addition/intramolecular cyclization process. 

PMID- 23876131
TI  - Comparison of white matter integrity between autism spectrum disorder subjects
      and typically developing individuals: a meta-analysis of diffusion tensor imaging
      tractography studies.
AB  - BACKGROUND: Aberrant brain connectivity, especially with long-distance
      underconnectivity, has been recognized as a candidate pathophysiology of autism
      spectrum disorders. However, a number of diffusion tensor imaging studies
      investigating people with autism spectrum disorders have yielded inconsistent
      results. METHODS: To test the long-distance underconnectivity hypothesis, we
      performed a systematic review and meta-analysis of diffusion tensor imaging
      studies in subjects with autism spectrum disorder. Diffusion tensor imaging
      studies comparing individuals with autism spectrum disorders with typically
      developing individuals were searched using MEDLINE, Web of Science and EMBASE
      from 1980 through 1 August 2012. Standardized mean differences were calculated as
      an effect size of the tracts. RESULTS: A comprehensive literature search
      identified 25 relevant diffusion tensor imaging studies comparing autism spectrum
      disorders and typical development with regions-of-interest methods. Among these,
      14 studies examining regions of interest with suprathreshold sample sizes were
      included in the meta-analysis. A random-effects model demonstrated significant
      fractional anisotropy reductions in the corpus callosum (P = 0.023, n = 387
      (autism spectrum disorders/typically developing individuals: 208/179)), left
      uncinate fasciculus (P = 0.011, n = 242 (117/125)), and left superior
      longitudinal fasciculus (P = 0.016, n = 182 (96/86)), and significant increases
      of mean diffusivity in the corpus callosum (P = 0.006, n = 254 (129/125)) and
      superior longitudinal fasciculus bilaterally (P = 0.031 and 0.011, left and
      right, respectively, n = 109 (51/58)), in subjects with autism spectrum disorders
      compared with typically developing individuals with no significant publication
      bias. CONCLUSION: The current meta-analysis of diffusion tensor imaging studies
      in subjects with autism spectrum disorders emphasizes important roles of the
      superior longitudinal fasciculus, uncinate fasciculus, and corpus callosum in the
      pathophysiology of autism spectrum disorders and supports the long-distance
      underconnectivity hypothesis.

PMID- 23876134
TI  - Dye stabilization and enhanced photoelectrode wettability in water-based dye
      sensitized solar cells through post-assembly atomic layer deposition of TiO2.
AB  - Detachment (desorption) of molecular dyes from photoelectrodes is one of the
      major limitations for the long-term operation of dye-sensitized solar cells. Here
      we demonstrate a method to greatly inhibit this loss by growing a transparent
      metal oxide (TiO2) on the dye-coated photoelectrode via atomic layer deposition
      (ALD). TiO2-enshrouded sensitizers largely resist detachment, even in pH 10.7
      ethanol, a standard solution for intentional removal of molecular dyes from
      photoelectrodes. Additionally, the ALD post-treatment renders the otherwise
      hydrophobic dye-coated surface hydrophilic, thereby enhancing photoelectrode pore
      filling with aqueous solution. 

PMID- 23876135
TI  - Assessment of Cryptococcus albidus for biopulping of eucalyptus.
AB  - Cryptococcus albidus shows delignification activity in nature. It was used for
      the biopulping of eucalyptus wood (Eucalyptus grandis) to access its potential
      for industrial application in the pulp and paper industry. Enzyme analysis on
      days 15, 30, and 60 showed the presence of laccase and xylanase as key enzymes.
      The production of endo-glucanase (CMCase) and exo-glucanase (FPase) was very low.
      Scanning electron microscopy (SEM) showed the surface colonization of wood and
      loosening of wood fibers in C. albidus-treated samples. Fourier-transformation
      infrared spectroscopy (FT-IR) indicated the chemical modification of eucalyptus
      wood. Denaturing gradient gel electrophoresis (DGGE) analysis on days 15, 30, and
      60 confirmed the presence of C. albidus throughout the experiments. Cryptococcu
      albidus was able to suppress the growth of a native population. Further, after 60
      days both the control and treated eucalyptus wood chips were given kraft pulping
      treatment. The kappa number of pulp of control wood was 21 and for treated wood
      was 17. Kappa number is considered a measure of lignin content in wood; hence the
      treatment of eucalyptus by C. albidus (biopulping) was effective in reducing its
      lignin content and can be used for biopulping in the pulp and paper industry. 

PMID- 23876136
TI  - Immobilization of bovine catalase onto magnetic nanoparticles.
AB  - The scope of this study is to achieve carrier-bound immobilization of catalase
      onto magnetic particles (Fe3O4 and Fe2O3NiO2 . H2O) to specify the optimum
      conditions of immobilization. Removal of H2O2 and the properties of immobilized
      sets were also investigated. To that end, adsorption and then cross-linking
      methods onto magnetic particles were performed. The optimum immobilization
      conditions were found for catalase: immobilization time (15 min for Fe3O4; 10 min
      for Fe2O3NiO2 . H2O), the initial enzyme concentration (1 mg/mL), amount of
      magnetic particles (25 mg), and glutaraldehyde concentration (3%). The activity
      reaction conditions (optimum temperature, optimum pH, pH stability, thermal
      stability, operational stability, and reusability) were characterized. Also
      kinetic parameters were calculated by Lineweaver-Burk plots. The optimum pH
      values were found to be 7.0, 7.0, and 8.0 for free enzyme, Fe3O4-immobilized
      catalases, and Fe2O3NiO2 . H2O-immobilized catalases, respectively. All
      immobilized catalase systems displayed the optimum temperature between 25 and 35
      degrees C. Reusability studies showed that Fe3O4-immobilized catalase can be used
      11 times with 50% loss in original activity, while Fe2O3NiO2 . H2O-immobilized
      catalase lost 67% of activity after the same number of uses. Furthermore,
      immobilized catalase systems exhibited improved thermal and pH stability. The
      results transparently indicate that it is possible to have binding between enzyme
      and magnetic nanoparticles.

PMID- 23876137
TI  - Statistical approach for the enhanced production of cold-active beta
      galactosidase from Thalassospira frigidphilosprofundus: a novel marine
      psychrophile from deep waters of Bay of Bengal.
AB  - In the present investigation Thalassospira frigidphilosprofundus, a novel species
      from the deep waters of the Bay of Bengal, was explored for the production of
      cold-active beta-galactosidase by submerged fermentation using marine broth
      medium as the basal medium. Effects of various medium constituents, namely,
      carbon, nitrogen source, pH, and temperature, were investigated using a
      conventional one-factor-at-a-time method. It was found that lactose, yeast
      extract, and bactopeptones are the most influential components for beta
      galactosidase production. Under optimal conditions, the production of beta
      galactosidase was found to be 3,864 U/mL at 20 +/- 2 degrees C, pH 6.5 +/- 0.2,
      after 48 hr of incubation. beta-Galactosidase production was further optimized by
      the Taguchi orthogonal array design of experiments and the central composite
      rotatable design (CCRD) of response surface methodology. Under optimal
      experimental conditions the cold-active beta-galactosidase enzyme production from
      Thalassospira frigidphilosprofundus was enhanced from 3,864 U/mL to 10,657 U/mL,
      which is almost three times higher than the cold-active beta-galactosidase
      production from the well-reported psychrophile Pseudoalteromonas haloplanktis. 

PMID- 23876138
TI  - Anticancer medicines (Doxorubicin and methotrexate) conjugated with magnetic
      nanoparticles for targeting drug delivery through iron.
AB  - The uptake of iron is increased by cancer cells. Iron magnetic nanoparticles
      (MNP) can be used as a nanovehicle for immobilization of anticancer medicines and
      to integrate them at a target site. The anticancer medicines doxorubicin (DOX)
      and methotrexate (MTX) were immobilized separately and in combination onto MNP by
      a glutaraldehyde activation method and confirmed by magnetic nanoparticles linked
      immunosorbent assay (MagLISA) and Fourier-transform infrared (FTIR) spectroscopy.
      The phenol peaks of DOX and MTX at 2896.6 cm-1 to 2912.5 cm-1 in FTIR spectra of
      immobilized medicines indicated the conjugation. Affinity-purified anti-DOX and
      anti-MTX antibodies were used to evaluate the coupling of DOX and MTX onto MNP,
      and the binding was found 34.6% to 37.2% and 51.8% to 54.3% separately,
      respectively. The immobilization of DOX and MTX in combination onto MNP was 18%
      and 27%, respectively. HeLa and B cells were cultured with DOX-MNP, MTX-MNP, and
      DOX-MNP-MTX separately, and MagLISA indicated that the binding of DOX-MNP/MTX-MNP
      was 41.5% to 45% with HeLa cells and 20% to 26% with B cells. No significant
      difference was observed in binding of DOX-MNP-MTX with HeLa and B cells. Results
      also indicated that the release of medicines at pH 5.0 is more (39% to 44%) than
      at pH 7.4 (3.7% to 10.2%). Sixteen to 22% more killing effect was observed on
      HeLa cells than on B cells. In immunohistochemical staining, more deposition of
      brown color on HeLa cells than on B cells may be due to more expression of iron
      binding sites on cancer cells. The dual property of MNP can be used for binding
      of medicines and for targeting drug delivery.

PMID- 23876139
TI  - Enzymatic surface hydrolysis of polyamide 6,6 with mixtures of proteolytic and
      lipolytic enzymes.
AB  - This study investigated the changes induced on nylon 6,6 fabric by a mixture of
      proteolytic and lipolytic enzymes. Technical measurements were studied including
      those of Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric
      analysis (TGA), weight loss (WL), bending lengths (BL), scanning electron
      microscopy (SEM), moisture absorbency (MA), and reflectance spectroscopy (RS).
      For this purpose, nylon 6,6 fabrics were treated separately with different
      concentrations of protease and lipase mixtures in solution. The dyeing process
      was then carried out on the treated fabrics with two reactive and acid dyes. The
      intensity of major peaks in the FTIR spectra of the protease-treated samples is
      in favor of chemical changes the polypeptide functional groups in the fabrics.
      Thermal studies also show a significant decrease in the thermal degradation
      temperature of the treated polymer at temperatures higher than 400 degrees C. The
      protease and lipase mixtures decreased the sample weight, while lipase
      intensified the weight loss comparing with protease. It was observed that the
      concentration of lipase enzyme had a direct influence on the darkness of dyed
      samples. 

PMID- 23876140
TI  - Sorption of ferrous and ferric iron by extracellular polymeric substances (EPS)
      from acidophilic bacteria.
AB  - The sorption of Fe(II) and Fe(III) by extracellular polymeric substances (EPS) of
      acidophilic bacteria Acidiphilium 3.2Sup(5) and Acidithiobacillus ferrooxidans,
      harvested from the ecosystem of the Tinto River (Huelva, Spain), was
      investigated. EPS from mixed cultures of both bacteria (EPS(mixed)) and pure
      cultures of A. 3.2Sup(5) (EPS(pure)) were extracted with ethylenediamine
      tetraacetic acid (EDTA) and were characterized by Fourier-transform infrared
      (FTIR), electron photoemission (XPS), x-ray diffraction (DRX), and energy
      dispersive x-ray (EDX) spectroscopy and scanning electron microscopy (SEM). EPS
      pure were loaded, in sorption tests, with Fe(II) and Fe(III). The results
      obtained indicate that the biochemical composition and structure of EPS(mixed)
      was very similar to that of EPS(pure). Besides, results indicate that EPS(mixed)
      adsorbed Fe(II) and Fe(III) by preferential interaction with the carboxyl group,
      which favored the formation of Fe(II)/Fe(III) oxalates. These species were also
      formed in EPS(pure) loaded with Fe(II)/Fe(III). All this behavior suggested that
      the sorption of iron by EPS(mixed) was similar to sorption of EPS(pure), which
      fitted the Freundlich model. Thus, the iron uptake of EPS(mixed) reached 516.7 +/
      23.4 mg Fe/g-EPS at an initial concentration of 2.0 g/L of Fe(total) and
      Fe(II)/Fe(III) ratio of 1.0.

PMID- 23876141
TI  - Effect of fermentation parameters on bio-alcohols production from glycerol using
      immobilized Clostridium pasteurianum: an optimization study.
AB  - This article addresses the issue of effect of fermentation parameters for
      conversion of glycerol (in both pure and crude form) into three value-added
      products, namely, ethanol, butanol, and 1,3-propanediol (1,3-PDO), by immobilized
      Clostridium pasteurianum and thereby addresses the statistical optimization of
      this process. The analysis of effect of different process parameters such as
      agitation rate, fermentation temperature, medium pH, and initial glycerol
      concentration indicated that medium pH was the most critical factor for total
      alcohols production in case of pure glycerol as fermentation substrate. On the
      other hand, initial glycerol concentration was the most significant factor for
      fermentation with crude glycerol. An interesting observation was that the
      optimized set of fermentation parameters was found to be independent of the type
      of glycerol (either pure or crude) used. At optimum conditions of agitation rate
      (200 rpm), initial glycerol concentration (25 g/L), fermentation temperature (30
      degrees C), and medium pH (7.0), the total alcohols production was almost equal
      in anaerobic shake flasks and 2-L bioreactor. This essentially means that at
      optimum process parameters, the scale of operation does not affect the output of
      the process. The immobilized cells could be reused for multiple cycles for both
      pure and crude glycerol fermentation. 

PMID- 23876143
TI  - Epidemiology of neurodegeneration in American-style professional football
      players.
AB  - The purpose of this article is to review the history of head injuries in relation
      to American-style football play, summarize recent research that has linked
      football head injuries to neurodegeneration, and provide a discussion of the next
      steps for refining the examination of neurodegeneration in football players. For
      most of the history of football, the focus of media reports and scientific
      studies on football-related head injuries was on the acute or short-term effects
      of serious, traumatic head injuries. Beginning about 10 years ago, a growing
      concern developed among neurologists and researchers about the long-term effects
      that playing professional football has on the neurologic health of the players.
      Autopsy-based studies identified a pathologically distinct neurodegenerative
      disorder, chronic traumatic encephalopathy, among athletes who were known to have
      experienced concussive and subconcussive blows to the head during their playing
      careers. Football players have been well represented in these autopsy findings. A
      mortality study of a large cohort of retired professional football players found
      a significantly increased risk of death from neurodegeneration. Further analysis
      found that non-line players were at higher risk than line players, possibly
      because of an increased risk of concussion. Although the results of the studies
      reviewed do not establish a cause effect relationship between football-related
      head injury and neurodegenerative disorders, a growing body of research supports
      the hypothesis that professional football players are at an increased risk of
      neurodegeneration. Significant progress has been made in the last few years on
      detecting and defining the pathology of neurodegenerative diseases. However, less
      progress has been made on other factors related to the progression of those
      diseases in football players. This review identifies three areas for further
      research: (a) quantification of exposure - a consensus is needed on the use of
      clinically practical measurements of blows to the head among football players;
      (b) genetic susceptibility factors - a more rigorous set of unbiased
      epidemiological and clinical studies is needed before any causal relationships
      can be drawn between suspected genetic factors, head injury, and
      neurodegeneration; and (c) earlier detection and prevention of neurodegenerative
      diseases. 

PMID- 23876145
TI  - Degradation of VX surrogate profenofos on surfaces via in situ photo-oxidation.
AB  - Surface degradation of profenofos (PF), a VX nerve gas surrogate, was
      investigated using in situ photo-oxidation that combines simple instrumentation
      and ambient gases (O2 and H2O) as a function of exposure conditions ([O3], [OH],
      UV light lambda = 185 and/or 254 nm, relative humidity) and PF film surface
      density (0.38-3.8 g m(-2)). PF film 0.38 g m(-2) fully degraded after 60 min of
      exposure to both 254 and 185 nm UV light in humidified air and high ozone. The
      observed pseudo-first-order surface reaction rate constant (kobs = 0.075 +/-
      0.004 min(-1)) and calculated hydroxyl concentration near the film surface ([OH]g
      = (9 +/- 2) * 10(7) molecules cm(-3)) were used to determine the second-order
      rate constant for heterogeneous reaction of PF and OH (k(OH)PF = (5 +/- 1) * 10(
      12) cm(3) molec(-1) s(-1)). PF degradation in the absence of 185 nm light or
      without humidity was lower (70% or 90% degradation, respectively). With denser PF
      films ranging from 2.3 to 3.8 g m(-2), only 80% degradation was achieved until
      the PF droplet was redissolved in acetonitrile which allowed >95% PF degradation.
      Surface product analysis indicated limited formation of the nontoxic phosphoric
      acid ester but the formation of nonvolatile chemicals with increased
      hydrophilicity and addition of OH. 

PMID- 23876146
TI  - Development, relative validity, and reliability of a food frequency questionnaire
      for a case-control study on dietary advanced glycation end products and diabetes
      complications.
AB  - Dietary advanced glycation end products (dAGEs) could be involved on diabetes
      complications, yet their quantification is not standardized. The objective of
      this study was to design a food frequency questionnaire (FFQ) for dAGEs, and to
      assess its reliability and validity. For the design, data from 30 subjects was
      used. The final instrument had 90 food items. To measure reliability and
      validity, 20 participants with type 2 diabetes filled out twice the FFQ (FFQ-T1,
      FFQ-T2) and 7-day food records (7-dFR). The Shrout-Fleiss coefficient was 0.98
      showing good reliability. For validation, the results for the weighted kappa were
      0.55 (moderate agreement) for FFQ-T1 and 0.64 (good agreement) for FFQ-T2, and
      75% and 80% of subjects respectively were correctly classified into tertiles;
      Bland-Altman graphics showed no systematic bias. This FFQ is comparable to 7-dFR
      for measuring dAGEs. To our knowledge, this is the first questionnaire designed
      to measure specifically dAGEs.

PMID- 23876144
TI  - Spinal muscular atrophy: a motor neuron disorder or a multi-organ disease?
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive disorder that is the
      leading genetic cause of infantile death. SMA is characterized by loss of motor
      neurons in the ventral horn of the spinal cord, leading to weakness and muscle
      atrophy. SMA occurs as a result of homozygous deletion or mutations in Survival
      Motor Neuron-1 (SMN1). Loss of SMN1 leads to a dramatic reduction in SMN protein,
      which is essential for motor neuron survival. SMA disease severity ranges from
      extremely severe to a relatively mild adult onset form of proximal muscle
      atrophy. Severe SMA patients typically die mostly within months or a few years as
      a consequence of respiratory insufficiency and bulbar paralysis. SMA is widely
      known as a motor neuron disease; however, there are numerous clinical reports
      indicating the involvement of additional peripheral organs contributing to the
      complete picture of the disease in severe cases. In this review, we have compiled
      clinical and experimental reports that demonstrate the association between the
      loss of SMN and peripheral organ deficiency and malfunction. Whether defective
      peripheral organs are a consequence of neuronal damage/muscle atrophy or a direct
      result of SMN loss will be discussed. 

PMID- 23876147
TI  - Mechanistic study of the biomimetic synthesis of flavonolignan diastereoisomers
      in milk thistle.
AB  - The mechanism for the biomimetic synthesis of flavonolignan diastereoisomers in
      milk thistle is proposed to proceed by single-electron oxidation of coniferyl
      alcohol, subsequent reaction with one of the oxygen atoms of taxifolin's catechol
      moiety, and finally, further oxidation to form four of the major components of
      silymarin: silybin A, silybin B, isosilybin A, and isosilybin B. This mechanism
      is significantly different from a previously proposed process that involves the
      coupling of two independently formed radicals. 

PMID- 23876148
TI  - Synergistic approach to high-performance oxide thin film transistors using a
      bilayer channel architecture.
AB  - We report here a bilayer metal oxide thin film transistor concept (bMO TFT) where
      the channel has the structure: dielectric/semiconducting indium oxide (In2O3)
      layer/semiconducting indium gallium oxide (IGO) layer. Both semiconducting layers
      are grown from solution via a low-temperature combustion process. The TFT
      mobilities of bottom-gate/top-contact bMO TFTs processed at T = 250  degrees C
      are ~5tmex larger (~2.6 cm(2)/(V s)) than those of single-layer IGO TFTs (~0.5
      cm(2)/(V s)), reaching values comparable to single-layer combustion-processed
      In2O3 TFTs (~3.2 cm(2)/(V s)). More importantly, and unlike single-layer In2O3
      TFTs, the threshold voltage of the bMO TFTs is ~0.0 V, and the current on/off
      ratio is significantly enhanced to ~1 * 10(8) (vs ~1 * 10(4) for In2O3). The
      microstructure and morphology of the In2O3/IGO bilayers are analyzed by X-ray
      diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and
      transmission electron microscopy, revealing the polycrystalline nature of the
      In2O3 layer and the amorphous nature of the IGO layer. This work demonstrates
      that solution-processed metal oxides can be implemented in bilayer TFT
      architectures with significantly enhanced performance.

PMID- 23876149
TI  - Type 1 sodium-dependent phosphate transporter acts as a membrane potential-driven
      urate exporter.
AB  - SLC17A1 protein (NPT1) was the first identified member of the SLC17 phosphate
      transporter family, and is known to mediate Na(+)/inorganic phosphate (Pi) co
      transport when expressed in Xenopus oocytes. Although this protein was suggested
      to be a renal polyspecific anion exporter, its transport properties were not well
      characterized. The clean biochemical approach revealed that proteoliposomes
      comprising purified NPT1 as the only protein source transport various organic
      anions such as urate, p-aminohippuric acid (PAH), and acetylsalicylic acid
      (aspirin) in a membrane potential (Deltapsi)-driven and Cl(-) -dependent manner.
      Human NPT1 carrying an SNP mutation, Thr269Ile, known to increase the risk of
      gout, exhibited 32% lower urate transport activity compared to the wild type
      protein, leading to the conclusion that NPT1 is the long searched for transporter
      responsible for renal urate excretion. In the present article, we summarized the
      history of identification of the urate exporter and its possible involvement in
      the dynamism of urate under physiological and pathological conditions. 

PMID- 23876150
TI  - SLC1 glutamate transporters and diseases: psychiatric diseases and pathological
      pain.
AB  - The solute carrier family 1 (SLC1) consists of two neutral amino acid
      transporters and five high-affinity excitatory amino acid transporters (EAAT1-5).
      EAATs are expressed in glial cells (EAAT1/GLAST and EAAT2/GLT-1), neurons
      (EAAT3/EAAC1 and EAAT4), and the retina (EAAT5), where they precisely regulate
      extracellular glutamate levels at both synaptic and extrasynaptic sites. EAATs
      play essential roles in the maintenance of normal excitatory synaptic
      transmission, protection of neurons from the excitotoxic action of excessive
      glutamate, and regulation of glutamatemediated neuroplasticity. Therefore,
      dysfunction of EAATs can cause abnormal excitatory synaptic transmission,
      neuronal excitotoxicity, and the exaggeration of neuroplasticity-based events.
      EAAT dysfunction has been implicated in a variety of neurodegenerative and
      neurological diseases, including amyotrophic lateral sclerosis, Parkinson's
      disease, Alzheimer's disease, ischemia, and epilepsy. Recent evidence suggests
      that abnormalities of EAATs contribute to the pathogenesis of psychiatric
      diseases and pathological pain. The present review will briefly discuss novel
      findings on the roles of EAATs in the pathogenesis of psychiatric diseases such
      as schizophrenia, mood disorders, and drug dependence/ addiction, and
      pathological pain, as well as the potential of EAATs as therapeutic targets. 

PMID- 23876151
TI  - Bile salt export pump (BSEP/ABCB11): trafficking and sorting disturbances.
AB  - Bile salt export pump (BSEP/ABCB11), a member of the family of ATP-binding
      cassette transporters, is localized on the canalicular membrane of hepatocytes
      and mediates the efficient biliary excretion of bile acid. The secretion of bile
      acid into bile by BSEP provides the primary osmotic driving force for bile flow
      generation. Intrahepatic cholestasis resulting from dysfunction of BSEP can be
      caused by a mutation in the gene encoding this protein or by acquired factors,
      such as the side effects of xenobiotics and drugs. In some pathophysiological
      states, inhibition of BSEP function is associated with its reduced expression on
      the canalicular membrane caused by impaired trafficking and sorting of BSEP. This
      fact has generated interest in better understanding the trafficking and sorting
      mechanism of BSEP. This review describes the molecular characteristics and
      physiological roles of BSEP, the trafficking and sorting machinery of BSEP, and
      the mechanisms responsible for disturbance of BSEP, which causes intrahepatic
      cholestasis. 

PMID- 23876152
TI  - Organic solute transporters and diseases: potential therapeutic targets.

PMID- 23876153
TI  - Diseases associated with general amino acid transporters of the solute carrier 6
      family (SLC6).
AB  - Amino acid transporters of the SLC6 family mediate the Na(+)-dependent uptake of
      neutral amino acids into neurons and epithelial cells of the intestine, kidney
      and other organs. They are integral parts of amino acid homeostasis in the whole
      body and the brain. In the intestine they are involved in protein absorption,
      while in the kidney they regulate plasma amino acid concentrations through
      reabsorption. The metabolic role of SLC6 amino acid transporters in the brain is
      less clear and most likely related to anaplerosis of the TCA cycle. Mutations in
      these transporters cause rare inherited disorders such as Hartnup disorder and
      iminoglycinuria. They may also play a role in complex traits such as depression,
      anxiety, obesity, diabetes and cancer. The review does not cover the transport of
      neurotransmitter amino acids. 

PMID- 23876154
TI  - Exploring insights for virulent gene inhibition of multidrug resistant Salmonella
      typhi, Vibrio cholerae, and Staphylococcus areus by potential phytoligands via in
      silico screening.
AB  - In our recent studies on prevalence of multidrug resistant pathogens in
      Byramangala reservoir, Karnataka, India, we identified Salmonella typhi,
      Staphylococcus aureus, and Vibrio cholerae which had acquired multiple drug
      resistance (MDR) and emerged as superbugs. Hence, there is a pressing demand to
      identify alternative therapeutic remedies. Our study focused on the screening of
      herbal leads by structure-based virtual screening. The virulent gene products of
      these pathogens towards Kanamycin(aph), Trimethoprim(dfrA1), Methicillin (mecI),
      and Vancomycin (vanH) were identified as the probable drug targets and their 3D
      structures were predicted by homology modeling. The predicted models showed good
      stereochemical validity. By extensive literature survey, we selected 58
      phytoligands and their drug likeliness and pharmacokinetic properties were
      computationally predicted. The inhibitory properties of these ligands against
      drug targets were studied by molecular docking. Our studies revealed that
      Baicalein from S. baicalensis (baikal skullcap) and Luteolin from Taraxacum
      officinale (dandelion) were identified as potential inhibitors against aph of S.
      typhi. Resveratrol from Vitis vinifera (grape vine) and Wogonin from S.
      baicalensis were identified as potential inhibitors against dfrA1 of S. typhi.
      Herniarin from Herniaria glabra (rupture worts) and Pyrocide from Daucus carota
      (Carrot) were identified as the best leads against dfrA1 of V. cholerae.
      Taraxacin of T. officinale (weber) and Luteolin were identified as potential
      inhibitors against Mec1. Apigenin from Coffee arabica (coffee) and Luteolin were
      identified as the best leads against vanH of S. aureus. Our findings pave crucial
      insights for exploring alternative therapeutics against MDR pathogens. 

PMID- 23876155
TI  - Stabilization of the CORA based leveling osteotomy for treatment of cranial
      cruciate ligament injury using a bone plate augmented with a headless compression
      screw.
AB  - OBJECTIVE: To report the effectiveness of a bone plate/headless compression screw
      (HCS) construct in preventing tibial plateau angle (TPA) shift postoperatively
      and to describe radiographic healing of the osteotomy. STUDY DESIGN: Case series.
      ANIMALS: Dogs (n = 31). METHODS: Records of dogs diagnosed with cranial cruciate
      ligament (CCL) injury treated with the center of rotation of angulation (CORA)
      based leveling osteotomy (CBLO) stabilized with a bone plate augmented with a HCS
      were reviewed. Breed, age, weight, and gender were recorded. Radiographs were
      reviewed for determination of preoperative tibial plateau angle (PreTPA),
      postoperative TPA (PostTPA), patellar tendon angle (PTA) postoperatively, and TPA
      at final evaluation (FinalTPA). Difference between PostTPA and FinalTPA was used
      to define any TPA shift. Radiographic healing at final evaluation was graded
      based on a 5-point scale. RESULTS: Mean time to final recheck was 88 days (range
      49-237 days) with mean +/- SD PreTPA = 28.6 +/- 4.8 degrees ; PostTPA = 9.2 +/-
      2.2 degrees ; FinalTPA = 9.7 +/- 2.6 degrees ; and TPA Shift = 0.52 +/- 1.61
      degrees . There was no significant difference between PostTPA and FinalTPA (P =
      .084, power > 0.80). Mean postoperative PTA was 89.9 +/- 1.7 degrees . There were
      2 implant related complications; 1 HCS migration and 1 HCS failure. CONCLUSION:
      Stabilization of the CBLO using a bone plate augmented with a HCS was effective
      in maintaining PostTPA and achieving satisfactory radiographic healing.

PMID- 23876156
TI  - A structural assessment of the 30-item Metacognitions Questionnaire for Children
      and its relations to anxiety symptoms.
AB  - Theoretical models of anxiety have been developed in adult populations. The
      applicability of these models in child samples has been assessed using downward
      extensions of the questionnaires developed to assess the proposed theoretical
      mechanisms. This poses a challenge, as children are still in the process of
      developing the skills that are being assessed. Psychometrically sound assessment
      tools are therefore needed for this developing population, in order to ensure the
      early detection of mechanisms leading to anxiety disorders in children. This
      study examined if metacognitions, which play a key role in generalized anxiety
      disorder (GAD) in adults, can also be reliably assessed in childhood. The study
      investigated the psychometric properties of the 30-item Metacognitions
      Questionnaire for Children (MCQ-C30; Gerlach, Adam, Marschke, & Melfsen, 2008) in
      a national sample of 974 children and adolescents (538 girls) ages 9-17 years.
      Confirmatory factor analysis supported the 5-factor subscale structure and a 2nd
      order total scale factor, which corresponds with previous versions of the scale.
      MCQ-C30 expectedly correlated significantly with anxiety symptoms and worry.
      Structural equation modeling revealed that both obsessive-compulsive disorder and
      generalized anxiety disorder symptoms regressed significantly onto the MCQ-C30.
      We fitted separate models for children and adolescents, and no noticeable
      differences are suggested between the models. Female gender was, expectedly,
      associated with increased levels of general metacognitions. This gender effect
      was mediated by level of anxiety. Overall, the MCQ-C30 exhibited acceptable
      psychometric properties in our community sample of children ages 9-17 years.
      Future studies should investigate the psychometric properties of the instrument
      in clinical samples and samples of younger children.

PMID- 23876157
TI  - Frequency of intrusions and flashbacks in patients with posttraumatic stress
      disorder related to childhood sexual abuse: an electronic diary study.
AB  - Intrusions and flashbacks are core features of posttraumatic stress disorder
      (PTSD). The frequency of these symptoms is usually assessed through retrospective
      questionnaires, which may be subject to recall bias of unknown magnitude.
      Electronic diaries that enable real-time assessment have been used to address
      recall biases in several psychiatric disorders. However, to our knowledge, this
      is the first study to apply this method to assess intrusions and flashbacks in
      PTSD related to childhood sexual abuse (CSA). Female patients with PTSD related
      to CSA (n = 28) were provided with electronic diaries for repeated real-time
      assessment of intrusions and flashbacks over the period of 1 week. At the end of
      this period, they were asked to retrospectively report how many such symptoms
      they recalled having experienced over the past week. The total number of symptoms
      reported in the electronic diaries (74.5 +/- 62.0 intrusions and 24.4 +/- 36.0
      flashbacks for the week) was substantially higher than those reported in previous
      studies. Furthermore, electronic diaries revealed the occurrence of about 50%
      more intrusions and flashbacks than did the retrospective assessment (74.5 vs.
      49.5 for intrusions, and 24.4 vs. 13.4 for flashbacks). Such high frequencies are
      not captured with existing assessment instruments and suggest a possible ceiling
      effect. Future research needs to clarify whether these high numbers are specific
      to highly symptomatic PTSD patients or might generalize to other populations of
      PTSD patients.

PMID- 23876158
TI  - Splanchnic vein thrombosis following renal transplantation: a case report.
AB  - BACKGROUND: Recurrent episodes of venous thrombosis have been closely correlated
      with JAK2 V617F mutation. Upto date, JAK2 gene mutation has not been defined as a
      prothrombic risk factor in renal transplant recipients. Herein; we present a case
      of portosplenic vein thrombosis in a primary renal transplant recipient with JAK2
      V617F mutation who had no history of prior venous thromboembolism or
      thrombophilia. CASE PRESENTATION: A 59 year old female caucasian patient with
      primary kidney transplant admitted with vague abdominal pain at left upper
      quadrant. Abdominal doppler ultrasound and magnetic resonance imaging angiography
      demonstrated splanchnic vein thrombosis (SVT). The final diagnosis was SVT due to
      MPD (essential thrombocytosis, ET) with JAK2 V617F mutation. After 3 months of
      treatment with warfarin (>=5 mg/day, to keep target INR values of 1.9-2.5),
      control MRI angiography and doppler USG demonstrated partial (>%50) resolution of
      thrombosis with recanalization of hepatopedal venous flow. The patient is still
      on the same treatment protocol without any complication. CONCLUSION: JAK2 V617F
      mutation analysis should be a routine procedure in the diagnosis and treatment of
      kidney transplant patients with thrombosis in uncommon sites.

PMID- 23876159
TI  - Acute peripartum twin-twin transfusion syndrome: incidence, risk factors,
      placental characteristics and neonatal outcome.
AB  - AIM: The aim of this study was to examine the incidence, placental
      characteristics and outcome in acute peripartum twin-twin transfusion syndrome
      (TTTS). MATERIAL AND METHODS: All consecutive cases of monochorionic (MC) twins
      admitted to our center were included in the study. We excluded cases with chronic
      TTTS or twin anemia polycythemia sequence. Acute peripartum TTTS was defined when
      the inter-twin hemoglobin difference at birth was >8 g/dL. RESULTS: A total of
      241 MC twin pregnancies were included in the study. Acute peripartum TTTS was
      detected in six cases (2.5%, 6/241). Vaginal delivery occurred more often in the
      acute peripartum TTTS group compared to the control group of uncomplicated MC
      pregnancies, 100% (6/6) versus 57% (135/235) (P = 0.002), respectively. Acute
      anemia was detected only in firstborn twins. Placental angioarchitecture in acute
      peripartum TTTS was similar to the placentas in the control group. CONCLUSIONS:
      The incidence of acute peripartum TTTS is low (2.5%). Birth order and mode of
      delivery appear to be associated with increased risk of acute peripartum TTTS.

PMID- 23876160
TI  - The advantages and limitations of trait analysis with GWAS: a review.
AB  - Over the last 10 years, high-density SNP arrays and DNA re-sequencing have
      illuminated the majority of the genotypic space for a number of organisms,
      including humans, maize, rice and Arabidopsis. For any researcher willing to
      define and score a phenotype across many individuals, Genome Wide Association
      Studies (GWAS) present a powerful tool to reconnect this trait back to its
      underlying genetics. In this review we discuss the biological and statistical
      considerations that underpin a successful analysis or otherwise. The relevance of
      biological factors including effect size, sample size, genetic heterogeneity,
      genomic confounding, linkage disequilibrium and spurious association, and
      statistical tools to account for these are presented. GWAS can offer a valuable
      first insight into trait architecture or candidate loci for subsequent
      validation. 

PMID- 23876161
TI  - BAG3 protects bovine papillomavirus type 1-transformed equine fibroblasts against
      pro-death signals.
AB  - In human cancer cells, BAG3 protein is known to sustain cell survival. Here, for
      the first time, we demonstrate the expression of BAG3 protein both in equine
      sarcoids in vivo and in EqS04b cells, a sarcoid-derived fully transformed cell
      line harbouring bovine papilloma virus (BPV)-1 genome. Evidence of a possible
      involvement of BAG3 in equine sarcoid carcinogenesis was obtained by
      immunohistochemistry analysis of tumour samples. We found that most tumour
      samples stained positive for BAG3, even though to a different grade, while normal
      dermal fibroblasts from healthy horses displayed very weak staining pattern for
      BAG3 expression. By siRNA technology, we demonstrate in EqS04b the role of BAG3
      in counteracting basal as well as chemical-triggered pro-death signals. BAG3 down
      modulation was indeed shown to promote cell death and cell cycle arrest in G0/G1.
      In addition, we found that BAG3 silencing sensitized EqS04b cells to
      phenethylisothiocyanate (PEITC), a promising cancer
      chemopreventive/chemotherapeutic agent present in edible cruciferous vegetables.
      Notably, such a pro-survival role of BAG3 was less marked in E. Derm cells, an
      equine BPV-negative fibroblast cell line taken as a normal counterpart.
      Altogether our findings might suggest a mutual cooperation between BAG3 and viral
      oncoproteins to sustain cell survival. 

PMID- 23876163
TI  - Photocurrent enhancement from diketopyrrolopyrrole polymer solar cells through
      alkyl-chain branching point manipulation.
AB  - Systematically moving the alkyl-chain branching position away from the polymer
      backbone afforded two new thieno[3,2-b]thiophene-diketopyrrolopyrrole (DPPTT-T)
      polymers. When used as donor materials in polymer:fullerene solar cells,
      efficiencies exceeding 7% were achieved without the use of processing additives.
      The effect of the position of the alkyl-chain branching point on the thin-film
      morphology was investigated using X-ray scattering techniques and the effects on
      the photovoltaic and charge-transport properties were also studied. For both
      solar cell and transistor devices, moving the branching point further from the
      backbone was beneficial. This is the first time that this effect has been shown
      to improve solar cell performance. Strong evidence is presented for changes in
      microstructure across the series, which is most likely the cause for the
      photocurrent enhancement. 

PMID- 23876162
TI  - High-throughput identification of reference genes for research and clinical RT
      qPCR analysis of breast cancer samples.
AB  - BACKGROUND: Quantification and normalization of RT-qPCR data critically depends
      on the expression of so called reference genes. Our goal was to develop a
      strategy for the selection of reference genes that utilizes microarray data
      analysis and combines known approaches for gene stability evaluation and to
      select a set of appropriate reference genes for research and clinical analysis of
      breast samples with different receptor and cancer status using this strategy.
      METHODS: A preliminary search of reference genes was based on high-throughput
      analysis of microarray datasets. The final selection and validation of the
      candidate genes were based on the RT-qPCR data analysis using several known
      methods for expression stability evaluation: comparative ?Ct method, geNorm,
      NormFinder and Haller equivalence test. RESULTS: A set of five reference genes
      was identified: ACTB, RPS23, HUWE1, EEF1A1 and SF3A1. The initial selection was
      based on the analysis of publically available well-annotated microarray datasets
      containing different breast cancers and normal breast epithelium from breast
      cancer patients and epithelium from cancer-free patients. The final selection and
      validation were performed using RT-qPCR data from 39 breast cancer biopsy
      samples. Three genes from the final set were identified by the means of
      microarray analysis and were novel in the context of breast cancer assay. We
      showed that the selected set of reference genes is more stable in comparison not
      only with individual genes, but also with a system of reference genes used in
      commercial OncotypeDX test. CONCLUSION: A selection of reference genes for RT
      qPCR can be efficiently performed by combining a preliminary search based on the
      high-throughput analysis of microarray datasets and final selection and
      validation based on the analysis of RT-qPCR data with a simultaneous examination
      of different expression stability measures. The identified set of reference genes
      proved to be less variable and thus potentially more efficient for research and
      clinical analysis of breast samples comparing to individual genes and the set of
      reference genes used in OncotypeDX assay.

PMID- 23876164
TI  - Uveitis risk following oral fluoroquinolone therapy: a nested case-control Study.
AB  - OBJECTIVE: To determine the risk of uveitis associated with the use of oral
      fluoroquinolones. METHODS: Nested case-control study of all patients who visited
      an ophthalmologist in British Columbia, Canada, between 2000 and 2007, as
      captured in the British Columbia Health Linked Database. RESULTS: A total 3383
      incident cases of uveitis and 33,830 corresponding controls were identified.
      Among patients who had used oral fluoroquinolones within the past 30 days, the
      adjusted relative risk of uveitis was 3.53 (95% CI, 2.84-4.39). However, the
      relative risk of uveitis among patients taking oral macrolides and beta-lactams
      was also significantly elevated. CONCLUSIONS: Our data do not provide convincing
      evidence of an association between fluoroquinolones and uveitis, as this study
      found an association between several classes of antibiotics and uveitis. It is
      possible that the systemic processes for which these antibiotics are being
      prescribed are in fact the inciting factors for the uveitis.

PMID- 23876165
TI  - Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid
      following intra-articular administration to exercised thoroughbred horses.
AB  - Methylprednisolone acetate (MPA) is commonly administered to performance horses,
      and therefore, establishing appropriate withdrawal times prior to performance is
      critical. The objectives of this study were to describe the plasma
      pharmacokinetics of MPA and time-related urine and synovial fluid concentrations
      following intra-articular administration to sixteen racing fit adult Thoroughbred
      horses. Horses received a single intra-articular administration of MPA (100 mg).
      Blood, urine, and synovial fluid samples were collected prior to and at various
      times up to 77 days postdrug administration and analyzed using tandem liquid
      chromatography-mass spectrometry (LC-MS/MS). Maximum measured plasma MPA
      concentrations were 6.06 +/- 1.57 at 0.271 days (6.5 h; range: 5.0-7.92 h) and
      6.27 +/- 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03-12.0 h) for horses that had
      synovial fluid collected (group 1) and those that did not (group 2),
      respectively. The plasma terminal half-life was 1.33 +/- 0.80 and 0.843 +/- 0.414
      days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 +/- 2.12
      (group 1) and 4.81 +/- 2.56 (group 2) in plasma and day 17 (group 1) and 14
      (group 2) in urine. MPA concentrations in synovial fluid remained above the limit
      of detection (LOD) for up to 77 days following intra-articular administration,
      suggesting that plasma and urine concentrations are not a good indicator of
      synovial fluid concentrations. 

PMID- 23876166
TI  - (un) Disciplining the nurse writer: doctoral nursing students' perspective on
      writing capacity.
AB  - In this article, we offer a perspective into how Canadian doctoral nursing
      students' writing capacity is mentored and, as a result, we argue is disciplined.
      We do this by sharing our own disciplinary and interdisciplinary experiences of
      writing with, for and about nurses. We locate our experiences within a broader
      discourse that suggests doctoral (nursing) students be prepared as stewards of
      the (nursing) discipline. We draw attention to tensions and effects of writing
      within (nursing) disciplinary boundaries. We argue that traditional approaches to
      developing nurses' writing capacity in doctoral programs both shepherds and
      excludes emerging scholarly voices, and we present some examples to illustrate
      this dual role. We ask our nurse colleagues to consider for whom nurses write,
      offering an argument that nurses' writing must ultimately improve patient care
      and thus would benefit from multiple voices in writing. 

PMID- 23876167
TI  - Psychometric evaluation of the Korean version of the Diabetes Self-efficacy Scale
      among South Korean older adults with type 2 diabetes.
AB  - AIMS AND OBJECTIVES: To evaluate the psychometric properties (reliability and
      validity) of the Korean version of the Diabetes Self-efficacy Scale among South
      Korean older adults with type 2 diabetes mellitus. BACKGROUND: Self-efficacy has
      been reported to be a key component of enhancing diabetes self-management, and
      many healthcare providers have paid attention to the instruments to accurately
      measure self-efficacy as related to diabetes self-management. DESIGN: A
      psychometric test of an instrument measuring self-efficacy as related to diabetes
      self-management. METHODS: A total of 278 Korean older adults with type 2 diabetes
      were recruited in one senior centre in Seoul, South Korea. The instrument
      included the Diabetes Self-efficacy Scale and the summary of the Diabetes Self
      care Activities. Item analyses, reliability including internal consistency and
      stability, and validity including exploratory factor analysis, confirmatory
      factor analysis, and hypothesised relationships test were used to examine the
      psychometric properties of the Korean version of the Diabetes Self-efficacy
      Scale. RESULTS: The item-total correlation coefficients of all items were >0.30
      and ranged from 0.47-0.73. The coefficient alpha for the internal consistency was
      0.89, and the intraclass correlation coefficient for the stability was 0.90. Two
      factors were extracted from the exploratory factor analysis (factor 1, self
      efficacy for diet-related self-management behaviours; factor 2, self-efficacy for
      diabetes self-management behaviours except diet), and the two-factor model for
      the confirmatory factor analysis had good fitness indices. The diabetes self
      efficacy scores were positively correlated with the level of diabetes self
      management. CONCLUSIONS: The findings supported that the Korean version of the
      Diabetes Self-efficacy Scale was reliable and valid in measuring self-efficacy as
      related to diabetes self-management in Korean older adults with type 2 diabetes.
      RELEVANCE TO CLINICAL PRACTICE: The Korean version of the Diabetes Self-efficacy
      Scale can allow healthcare providers to effectively measure self-efficacy related
      to diabetes self-management so that they can provide the appropriate and adequate
      nursing care to Korean older adults with type 2 diabetes.

PMID- 23876168
TI  - Current and prospective treatments for multidrug-resistant gram-positive
      infections.
AB  - INTRODUCTION: Staphylococcus aureus and Enterococcus spp. are two of the most
      common organisms causing nosocomial infections today; and are consistently
      associated with high mortality rates (approximately 20 and 44%, respectively).
      Resistance among these pathogens to first line agents such as methicillin and
      vancomycin continues to rise while isolates with reduced susceptibility to newer
      agents including linezolid and daptomycin continue to emerge, representing a
      serious concern for clinicians. AREAS COVERED: Mechanisms of action and
      resistance as well as in vitro and clinical experience in the treatment of
      resistant staphylococci and enterococci with currently available agents are
      discussed. Additionally, novel combination regimens showing enhanced efficacy and
      available data pertaining to prospective therapies including solithromycin,
      tedizolid, dalbavancin and oritavancin will be covered. EXPERT OPINION: With an
      increase in organisms displaying reduced susceptibility to vancomycin and the
      associated treatment failures, the significance of alternative therapies such as
      daptomycin, linezolid, ceftaroline, and prospective anti-gram-positive agents is
      on the rise. As our understanding of antimicrobial pharmacokinetic
      pharmacodynamics principles continues to evolve, the selection of highly
      effective agents and optimization of dosages may lead to improved patient
      outcomes and delay the development of resistance.

PMID- 23876169
TI  - Quantitative evaluation of CXCL8 and its receptors (CXCR1 and CXCR2) gene
      expression in Iranian patients with multiple sclerosis.
AB  - CXCL8 and its receptors (CXCR1 and CXCR2) play important roles in CNS
      development, neuronal survival, modulation of excitability, and neuroimmune
      response. The aim of this study is to evaluate gene expression of CXCL8 and
      CXCR1/CXCR2 in peripheral blood cells (PBCs) of Iranian patients with relapsing
      remitting (RR) form of Multiple sclerosis (MS). We explored the mRNA expression
      of CXCL8 and its receptors in PBCs of 49 RR-MS patients in remitting status and
      60 healthy controls by quantitative Real-Time PCR. Median expression of CXCL8
      mRNA in peripheral blood of MS patients decreased more than 3-fold compared to
      control group (p < 0.001), while there were not significant differences in CXCR1
      and CXCR2 gene expression between MS patients and healthy subjects (p = 0.159 and
      p = 0.248, respectively). There was a significant negative correlation of CXCR2
      expression with EDSS (rs = -0.432, p = 0.004). It appears that decreased
      expression of CXCL8 may lead to a raised risk of MS. 

PMID- 23876170
TI  - Foaling rates after surgical repair of ventral cervical lacerations using a
      Trendelenburg position in 18 anesthetized mares.
AB  - OBJECTIVE: To (1) describe a surgical technique for repair of lacerations of the
      ventral aspect of the cervix in anesthetized mares in Trendelenburg position; and
      (2) report conception rates and foaling after repair. STUDY DESIGN: Case series.
      ANIMALS: Mares (n = 18). METHODS: Cervical lacerations were repaired in 2 layers
      with anesthetized mares in Trendelenburg position. The cervix was retracted
      caudally with stay-sutures, and after excision of the healed margin of the
      laceration, the internal cervical mucosa and fibromuscular tissue were sutured in
      1 layer with a continuous Lembert pattern. The external cervical mucosa was
      sutured using a simple-continuous suture pattern. Number of foals produced by
      each mare before and after surgical repair was obtained from client/farm
      communication and from a commercial record keeping service. RESULTS: Mean repair
      time for 1 laceration was 22 minutes and for 2 lacerations was 29 minutes. Nine
      mares conceived and 7 had at least 1 live healthy foal. CONCLUSION: Trendelenburg
      position allows for efficient repair of a ventrally located cervical laceration
      in anesthetized mares.

PMID- 23876171
TI  - Internal jugular venous abnormalities in transient monocular blindness.
AB  - BACKGROUND: The etiology of transient monocular blindness (TMB) in patients
      without carotid stenosis has been linked to ocular venous hypertension, for their
      increased retrobulbar vascular resistance, sustained retinal venule dilatation
      and higher frequency of jugular venous reflux (JVR). This study aimed to
      elucidate whether there are anatomical abnormalities at internal jugular vein
      (IJV) in TMB patients that would contribute to impaired cerebral venous drainage
      and consequent ocular venous hypertension. METHODS: Contrast-enhanced axial T1
      weighted magnetic resonance imaging (MRI) was performed in 23 TMB patients who
      had no carotid stenosis and 23 age- and sex-matched controls. The veins were
      assessed at the upper IJV (at C1-3 level) and the middle IJV (at C3-5 level).
      Grading of IJV compression/stenosis was determined bilaterally as follows: 0 =
      normal round or ovoid appearance; 1 = mild flattening; 2 = moderate flattening;
      and 3 = severe flattening or not visualized. RESULTS: There was significantly
      more moderate or severe IJV compression/stenosis in the TMB patients at the left
      upper IJV level and the bilateral middle IJV level. Defining venous
      compression/stenosis scores >= 2 as a significant cerebral venous outflow
      impairment, TMB patients were found to have higher frequency of significant
      venous outflow impairment at the upper IJV level (56.5% vs. 8.7%, p = 0.0005) and
      the middle IJV level (69.6% vs. 21.7%, p=0.0011). CONCLUSIONS: TMB Patients with
      the absence of carotid stenosis had higher frequency and greater severity of IJV
      compression/stenosis which could impair cerebral venous outflow. Our results
      provide evidence supporting that the cerebral venous outflow abnormality is one
      of the etiologies of TMB.

PMID- 23876172
TI  - Coicenals A-D, four new diterpenoids with new chemical skeletons from the plant
      pathogenic fungus Bipolaris coicis.
AB  - Coicenals A-C (1-3) possessing a previously undescribed 10-(sec-butyl)-6-hydroxy
      1,7,9-trimethyl-1,6,7,8,9,9a-hexahydro-1,4-methanobenzo[d]oxepin-2(4H)
      ylidene)acetaldehyde skeleton and coicenal D (4) with a new 2-(sec-butyl)-5
      hydroxy-1,6,8-trimethyl-2,5,6,7,8,8a-hexahydro-1H-4a,1-(epoxymethano)naphthalen
      10-ylidene)acetaldehyde skeleton were isolated from the solid culture of the
      plant pathogenic fungus Bipolaris coicis. The absolute configurations in 1 and 4
      were assigned by electronic circular dichroism (ECD) calculations. Compounds 1
      and 2 were transformed into 4 and 5 by treatment with acetyl chloride,
      respectively. Compounds 1-4 showed moderate inhibitory activity against NO
      release with IC50 values of 16.34 +/- 1.12, 23.55 +/- 1.37, 10.82 +/- 0.83, and
      54.20 +/- 2.82 MUM, respectively. 

PMID- 23876173
TI  - Surface passivation of gallium nitride by ultrathin RF-magnetron sputtered Al2O3
      gate.
AB  - An ultrathin RF-magnetron sputtered Al2O3 gate on GaN subjected to postdeposition
      annealing at 800  degrees C in O2 ambient was systematically investigated. A
      cross-sectional energy-filtered transmission electron microscopy revealed
      formation of crystalline Al2O3 gate, which was supported by X-ray diffraction
      analysis. Various current conduction mechanisms contributing to leakage current
      of the investigated sample were discussed and correlated with metal-oxide
      semiconductor characteristics of this sample. 

PMID- 23876174
TI  - Acquired microcystic lymphatic malformation of the distal upper extremity
      mimicking verrucae vulgaris.
AB  - An 18-year-old African American male with a history of congenital lymphedema of
      the right upper extremity presented for evaluation of multiple verrucous lesions
      on his right hand. Clusters of 2 to 4-mm dome-shaped vesicles were intermixed
      with scattered verrucous papules on the right forearm and the dorsal and palmar
      aspects of the hand. Histopathology of one the verrucous lesions showed well
      circumscribed areas of dilated lymphatic vascular channels with lymph in the
      lumen. The patient was diagnosed with microcystic lymphatic malformation,
      verrucous type. This article reviews the literature regarding reports of this
      variant of microcystic lymphatic malformation in the pediatric population. 

PMID- 23876175
TI  - Molecular targeting of hepatocyte growth factor by an antagonist, NK4, in the
      treatment of rheumatoid arthritis.
AB  - INTRODUCTION: Hepatocyte growth factor (HGF) is a potent proangiogenic molecule
      that induces neovascularization. The HGF antagonist, NK4, competitively
      antagonizes HGF binding to its receptor. In the present study, we determined the
      inhibitory effect of NK4 in a rheumatoid arthritis (RA) model using SKG mice.
      METHODS: Arthritis was induced in SKG mice by a single intraperitoneal injection
      of beta-glucan. Recombinant adenovirus containing NK4 cDNA (AdCMV.NK4) was also
      injected intravenously at the time of or 1 month after beta-glucan injection.
      Ankle bone destruction was examined radiographically. The histopathologic
      features of joints were examined using hematoxylin and eosin and
      immunohistochemical staining. Enzyme-linked immunosorbent assays were used to
      determine the serum levels of HGF, interferon gamma (IFN-gamma, interleukin 4 (IL
      4) and IL-17 production by CD4+ T cells stimulated with allogeneic spleen cells.
      RESULTS: The intravenous injection of AdCMV.NK4 into SKG mice suppressed the
      progression of beta-glucan-induced arthritis. Bone destruction was also inhibited
      by NK4 treatment. The histopathologic findings of the ankles revealed that
      angiogenesis, inflammatory cytokines and RANKL expression in synovial tissues
      were significantly inhibited by NK4 treatment. Recombinant NK4 (rNK4) proteins
      inhibited IFN-gamma, IL-4 and IL-17 production by CD4+ T cells stimulated with
      allogeneic spleen cells. CONCLUSIONS: These results indicate that NK4 inhibits
      arthritis by inhibition of angiogenesis and inflammatory cytokine production by
      CD4+ T cells. Therefore, molecular targeting of angiogenic inducers by NK4 can
      potentially be used as a novel therapeutic approach for the treatment of RA.

PMID- 23876176
TI  - Sounds in the ocean at 1-100 Hz.
AB  - Very-low-frequency sounds between 1 and 100 Hz propagate large distances in the
      ocean sound channel. Weather conditions, earthquakes, marine mammals, and
      anthropogenic activities influence sound levels in this band. Weather-related
      sounds result from interactions between waves, bubbles entrained by breaking
      waves, and the deformation of sea ice. Earthquakes generate sound in geologically
      active regions, and earthquake T waves propagate throughout the oceans. Blue and
      fin whales generate long bouts of sounds near 20 Hz that can dominate regional
      ambient noise levels seasonally. Anthropogenic sound sources include ship
      propellers, energy extraction, and seismic air guns and have been growing
      steadily. The increasing availability of long-term records of ocean sound will
      provide new opportunities for a deeper understanding of natural and anthropogenic
      sound sources and potential interactions between them. 

PMID- 23876177
TI  - "Everyone just keeps their eyes closed and their fingers crossed": sexual health
      communication among black parents and children in Nova Scotia, Canada.
AB  - BACKGROUND: Black Canadian youth remain disproportionally affected by an array of
      social and health issues, including sexually transmitted infections. While
      research exists in support of the involvement of parents as a key means to
      prevent or modify harmful behaviours among youth, less is known about how parent
      child communication can serve as a prevention intervention strategy within Black
      families in Canada. This study explores sexual health communication between Black
      parents and youth in Nova Scotia and identifies facilitators, obstacles and
      issues that families face in dialoguing about sexual health. METHODS: Focus
      groups and in-depth interview sessions were held with a diverse sample of parents
      of Black youth, health and education professionals, and Black youth in Nova
      Scotia, as part of a larger study aimed at exploring parent-child communication
      on sexual health and HIV. The research team worked in partnership with and
      received feedback from key informants and a community advisory committee
      throughout the various stages of this study. All sessions were audio-taped with
      permission and thematic analysis was carried out on the verbatim transcripts.
      RESULTS: Six key themes emerged from the data analysis in relation to parent
      child communication within Black families in Nova Scotia: 1. the gendered nature
      of [sexual] health communication; 2. fear and uncertainty as obstacles; 3. open
      and honest dialogue from an early age as a facilitator; 4. media as both a
      catalyst and a barrier; 5. peers as a catalyst; and 6. time constraints as an
      obstacle. CONCLUSIONS: The findings of this study reveal that parent-child
      communication regarding sexual health promotion within Black families in Nova
      Scotia remains varied and is heavily affected by a myriad of intersecting
      determinants of health faced by Black youth and their parents. Health promotion
      interventions aimed at fostering and supporting parent-child communication on
      sexual health must simultaneously target both parents and youth and further, such
      efforts must engage a high level of cultural competency in order to better meet
      the needs of this population.

PMID- 23876178
TI  - Exploring correlates of burnout dimensions in a sample of psychiatric
      rehabilitation practitioners: a cross-sectional study.
AB  - OBJECTIVE: The primary purpose of this article is to investigate demographic and
      work-related correlates of three burnout dimensions, that is, emotional
      exhaustion, depersonalization, and diminished personal accomplishment, using a
      national sample of psychiatric rehabilitation practitioners (PRPs). METHOD: An
      online survey was filled out by 1,639 PRPs who provided demographic, work
      related, and burnout data. Complete data for hypotheses testing using stepwise
      regression analyses was available for 813 PRPs. RESULTS: Lower than expected
      levels of burnout dimensions were found among PRPs. All 3 study hypotheses were
      at least partially supported. Looking at individual correlates of burnout
      dimensions, education level was positively related to emotional exhaustion, age
      was negatively related to depersonalization, and age and length of service were
      both negatively related to diminished personal accomplishment. Personal
      involvement was positively related to emotional exhaustion and depersonalization.
      Regression results were also supportive of the mental health burnout process
      model, that is, emotional exhaustion explaining depersonalization, which then
      combined with emotional exhaustion to help further explain diminished personal
      accomplishment. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Study limitations are
      acknowledged. This study updates the results of a prior 1996 PRP survey
      (Blankertz & Robinson, 1996) using a demographically comparable (i.e., gender,
      race, education level, primary area of study) sample. Reducing one's personal
      involvement with clients seems important to reducing PRP emotional exhaustion and
      depersonalization. Emotional exhaustion is generally acknowledged to be the key
      component to burnout and reducing it via peer support group sessions is
      recommended.

PMID- 23876179
TI  - Healthy living? By whose standards? Engaging mental health service recipients to
      understand their perspectives of, and barriers to, healthy living.
AB  - OBJECTIVE: It is well recognized that mental health service recipients experience
      high rates of cardiometabolic disorders, have poorer diets, and exercise less
      than the general population. This study sought to explore the meaning of a
      healthy lifestyle for this population and the barriers they experience to healthy
      living. METHOD: Focus groups were conducted with 23 individuals who experience
      serious mental health issues. The meaning of a healthy lifestyle and the barriers
      participants experience to living healthily were explored. RESULTS: Participants
      perceived a healthy lifestyle in broader terms than professional guidelines for
      exercise and diet. A broad framework including friendship, affordable safe
      housing, employment, spiritual, and emotional good health, as well as healthy
      eating and exercise, is described. Barriers identified by participants were poor
      mental and physical health and stigma (structural, social, and self). An
      unexpected result was the group problem solving that occurred during the focus
      groups. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Health care professionals need
      to understand mental health service recipients' perspectives of a "healthy
      lifestyle." An understanding of barriers within this context is required, as only
      then will we be able to empathize and assist as health care professionals. This
      study also shows that realistic, innovative, and pragmatic solutions occur when
      mental health service recipients are empowered.

PMID- 23876180
TI  - Plot protein: visualization of mutations.
AB  - BACKGROUND: Next-generation sequencing has enabled examination of variation at
      the DNA sequence level and can be further enhanced by evaluation of the variants
      at the protein level. One powerful method is to visualize these data often
      revealing patterns not immediately apparent in a text version of the same data.
      Many investigators are interested in knowing where their amino acid changes
      reside within a protein. Clustering of variation within a protein versus non
      clustering can show interesting aspects of the biological changes happening in
      disease. FINDING: We describe a freely available tool, Plot Protein, executable
      from the command line or utilized as a graphical interface through a web browser,
      to enable visualization of amino acid changes at the protein level. This allows
      researchers to plot variation from their sequencing studies in a quick and
      uniform way. The features available include plotting amino acid changes, domains,
      post-translational modifications, reference sequence, conservation, conservation
      score, and also zoom capabilities. Herein we provide a case example using this
      tool to examine the RET protein and we demonstrate how clustering of mutations
      within the protein in Multiple Endocrine Neoplasia 2A (MEN2A) reveals important
      information about disease mechanism. CONCLUSIONS: Plot Protein is a useful tool
      for investigating amino acid changes and their localization within proteins.
      Command line and web server versions of this software are described that enable
      users to derive visual knowledge about their mutations.

PMID- 23876181
TI  - Cross-sectional study of gestational weight gain and perinatal outcomes in
      pregnant women at a tertiary care center in southern India.
AB  - AIM: The aim of this study was to determine maternal and neonatal outcomes of
      less than recommended or excess gestational weight gain (GWG) based on the
      recommended Institute of Medicine (IOM) guidelines. MATERIAL AND METHODS: Using a
      cross-sectional study design, GWG was assessed for 1462 pregnant women presenting
      to a tertiary care perinatal institute in India. Body mass index at baseline, co
      existing morbidities, fetal growth, details of delivery, and maternal and fetal
      outcomes were determined and documented. Appropriate GWG for each woman was
      determined based on the revised IOM guidelines. Outcome measures included the
      proportion of pregnant women compliant with IOM guidelines for GWG and
      associations of less than recommended or excess GWG with maternal and neonatal
      outcomes. RESULTS: A total of 547 (37.41%, 95% confidence interval [CI]: 34.96
      39.92) pregnant women gained less than recommended and 313 (21.41%, 95%CI: 19.36
      23.57) pregnant women gained more than the recommended weight. Preterm deliveries
      were associated with less than optimal weight gain (adjusted odds ratio 3.58,
      95%CI: 1.75-7.32) after adjusting for gestational age at delivery. GWG was not
      associated with neonatal outcomes in this population. CONCLUSIONS: The lack of
      associations with perinatal outcomes indicates that the IOM guidelines may not be
      the appropriate standard for monitoring GWG in this population.

PMID- 23876182
TI  - Description of a double centrifugation tube method for concentrating canine
      platelets.
AB  - BACKGROUND: To evaluate the efficiency of platelet-rich plasma preparations by
      means of a double centrifugation tube method to obtain platelet-rich canine
      plasma at a concentration at least 4 times higher than the baseline value and a
      concentration of white blood cells not exceeding twice the reference range. A
      complete blood count was carried out for each sample and each concentrate. Whole
      blood samples were collected from 12 clinically healthy dogs (consenting blood
      donors). Blood was processed by a double centrifugation tube method to obtain
      platelet concentrates, which were then analyzed by a flow cytometry haematology
      system for haemogram. Platelet concentration and white blood cell count were
      determined in all samples. RESULTS: Platelet concentration at least 4 times
      higher than the baseline value and a white blood cell count not exceeding twice
      the reference range were obtained respectively in 10 cases out of 12 (83.3%) and
      11 cases out of 12 (91.6%). CONCLUSIONS: This double centrifugation tube method
      is a relatively simple and inexpensive method for obtaining platelet-rich canine
      plasma, potentially available for therapeutic use to improve the healing process.

PMID- 23876183
TI  - Intraocular cysts of toxoplasma gondii in patients with necrotizing retinitis
      following periocular/intraocular triamcinolone injection.
AB  - PURPOSE: To report the detection of Toxoplasma gondii cysts in intraocular
      aspirates of patients with necrotizing retinitis following periocular/intraocular
      corticosteroid injection. DESIGN: Case report. METHODS: Two patients (2 eyes)
      with widespread necrotizing retinitis in a steroid-exposed eye posed a diagnostic
      challenge and underwent pars plana vitrectomy (PPV). Intraocular samples
      (vitreous fluid, retinal tissue, and subretinal aspirate in case 1, and vitreous
      fluid in case 2) were subjected to cytological examination. RESULTS: The
      subretinal aspirate (case 1) revealed encysted bradyzoites of Toxoplasma gondii.
      Vitreous fluid (case 2) tested positive for anti-toxoplasma antibodies and the
      smear showed encysted forms of Toxoplasma gondii on cytology. CONCLUSION.
      Toxoplasma gondii cysts were detected in eyes with necrotizing retinitis that
      developed secondary to injudicious use of corticosteroids.

PMID- 23876184
TI  - Effect of species, breed and route of virus inoculation on the pathogenicity of
      H5N1 highly pathogenic influenza (HPAI) viruses in domestic ducks.
AB  - H5N1 highly pathogenic avian influenza (HPAI) viruses continue to be a threat to
      poultry in many regions of the world. Domestic ducks have been recognized as one
      of the primary factors in the spread of H5N1 HPAI. In this study we examined the
      pathogenicity of H5N1 HPAI viruses in different species and breeds of domestic
      ducks and the effect of route of virus inoculation on the outcome of infection.
      We determined that the pathogenicity of H5N1 HPAI viruses varies between the two
      common farmed duck species, with Muscovy ducks (Cairina moschata) presenting more
      severe disease than various breeds of Anas platyrhynchos var. domestica ducks
      including Pekin, Mallard-type, Black Runners, Rouen, and Khaki Campbell ducks. We
      also found that Pekin and Muscovy ducks inoculated with two H5N1 HPAI viruses of
      different virulence, given by any one of three routes (intranasal, intracloacal,
      or intraocular), became infected with the viruses. Regardless of the route of
      inoculation, the outcome of infection was similar for each species but depended
      on the virulence of the virus used. Muscovy ducks showed more severe clinical
      signs and higher mortality than the Pekin ducks. In conclusion, domestic ducks
      are susceptible to H5N1 HPAI virus infection by different routes of exposure, but
      the presentation of the disease varied by virus strain and duck species. This
      information helps support the planning and implementation of H5N1 HPAI
      surveillance and control measures in countries with large domestic duck
      populations. 

PMID- 23876185
TI  - The performance of an online osteoporosis detection system a sensitivity and
      specificity analysis.
AB  - AIMS AND OBJECTIVES: To develop an online system for the detection of
      osteoporosis risk and to test its accuracy. BACKGROUND: Osteoporosis is a silent
      killer; usually, there are no symptoms, such as pain, until bone erosion and
      fracture occur. The risks of osteoporosis have been underestimated and neglected;
      as a result, osteoporosis can be as dangerous as heart diseases and cancers that
      lead to a healthcare crisis. DESIGN: Cross-sectional study. METHODS: The study
      participants were individuals presenting for routine health examinations at a
      medical centre in Taiwan from 2006-2007. Women over 30 years of age who underwent
      dual-energy X-ray absorptiometry scanning for measurement of bone mineral density
      were eligible for this study. The system for osteoporosis detection and health
      risk, which was developed in this study, was analysed. RESULTS: The findings
      indicated a high sensitivity of 75%, specificity of 75%, positive predictive
      value of 75% and negative predictive value of 75%. In addition, the online
      osteoporosis detective system had a higher predictive power (24.2% vs. 11%) and a
      similar cut-off point (33% vs. 27%) compared with the tool designed by the
      International Osteoporosis Foundation. CONCLUSION: The online system for
      detection of osteoporosis risk had excellent reliability and validity. It
      performed well in predicting osteoporosis and the cut-off point used for
      identifying the risk among women at risk of developing osteoporosis. Therefore,
      it is suitable for the Asian women and can help women achieve the goals of early
      detection and health promotion. RELEVANCE TO CLINICAL PRACTICE: Early detection
      is the only way to prevent osteoporosis. Professional nurses should apply
      effective technology to promote health care in community-dwelling people.

PMID- 23876186
TI  - Translation: screening for novel therapeutics with disease-relevant cell types
      derived from human stem cell models.
AB  - The advent of somatic cell reprogramming technologies-which enables the
      generation of patient-specific, induced pluripotent stem cell and other trans
      differentiated human neuronal cell models-provides new means of gaining insight
      into the molecular mechanisms and neural substrates of psychiatric disorders. By
      allowing a more precise understanding of genotype-phenotype relationship in
      disease-relevant human cell types, the use of reprogramming technologies in
      tandem with emerging genome engineering approaches provides a previously "missing
      link" between basic research and translational efforts. In this review, we
      summarize advances in applying human pluripotent stem cell and reprogramming
      technologies to generate specific neural subtypes with a focus on the use of
      these in vitro systems for the discovery of small molecule-probes and novel
      therapeutics. Examples are given where human cell models of psychiatric disorders
      have begun to reveal new mechanistic insight into pathophysiology and
      simultaneously have provided the foundation for developing disease-relevant,
      phenotypic assays suitable for both functional genomic and chemical screens. A
      number of areas for future research are discussed, including the need to develop
      robust methodology for the reproducible, large-scale production of disease
      relevant neural cell types in formats compatible with high-throughput screening
      modalities, including high-content imaging, multidimensional, signature-based
      screening, and in vitro network with multielectrode arrays. Limitations,
      including the challenges in recapitulating neurocircuits and non-cell autonomous
      phenotypes are discussed. Although these technologies are still in active
      development, we conclude that, as our understanding of how to efficiently
      generate and probe the plasticity of patient-specific stem models improves, their
      utility is likely to advance rapidly. 

PMID- 23876187
TI  - Acute gastroenteritis surveillance through the National Outbreak Reporting
      System, United States.
AB  - Implemented in 2009, the National Outbreak Reporting System provides surveillance
      for acute gastroenteritis outbreaks in the United States resulting from any
      transmission mode. Data from the first 2 years of surveillance highlight the
      predominant role of norovirus. The pathogen-specific transmission pathways and
      exposure settings identified can help inform prevention efforts. 

PMID- 23876188
TI  - HMB attenuates muscle loss during sustained energy deficit induced by calorie
      restriction and endurance exercise.
AB  - OBJECTIVE: To investigate the efficacy and underlying mechanisms of beta-hydroxy
      beta-methylbutyrate (HMB) on body composition, muscle mass and physical
      performance under catabolic versus normal training conditions. MATERIALS/METHODS:
      Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1
      h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (
      30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments
      included body composition, grip strength and sensorimotor coordination before and
      after the experimental protocol, while in vitro analyses included muscle wet
      weights, expression of selected genes and proteins regulating muscle mass, and
      myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05.
      RESULTS: ALTH had greater lean mass than ALT and sensorimotor function increased
      in ALTH, but decreased in ALT under normal training conditions. Grip strength
      decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber
      CSA were greater in CH than C following catabolic conditions. Gastrocnemius
      atrogin-1 mRNA expression was elevated in C but not in CH compared to all other
      groups whereas atrogin-1 protein levels showed no significant changes.
      CONCLUSION: HMB improves body composition and sensorimotor function during normal
      training and attenuates muscle mass and strength loss during catabolic
      conditions.

PMID- 23876189
TI  - Antimicrobial susceptibility and genetic diversity of Streptococcus agalactiae
      recovered from newborns and pregnant women in Brazil.
AB  - BACKGROUND: Streptococcus agalactiae is known to be the major cause of neonatal
      infections and also causes complications during pregnancy. METHODS: One hundred
      and six strains of Streptococcus agalactiae recovered from clinical specimens of
      newborns (n = 18) and pregnant women (n = 88) were submitted to antimicrobial
      susceptibility testing and investigation of genetic determinants of macrolide
      resistance, capsular type, and virulence factors. Genetic diversity was evaluated
      by pulsed-field gel electrophoresis (PFGE) analysis. RESULTS: Strains were
      susceptible to ceftriaxone, levofloxacin, penicillin G, and vancomycin and
      resistant to tetracycline (85.8%) and erythromycin (4.7%). Erythromycin-resistant
      strains presented iMLSB phenotype, harbored the ermA gene, and were closely
      related by PFGE. Both bac and bca genes were found in low frequencies. PFGE
      analysis yielded 11 DNA restriction profiles among 35 selected isolates. The
      major clonal group, designated as A, was composed predominantly of strains
      belonging to capsular type Ia. Clonal group B was composed predominantly of
      strains with capsular type V, including all erythromycin-resistant isolates.
      CONCLUSIONS: Although low levels of erythromycin resistance have been observed,
      this is a fact of concern because this phenotype also confers resistance to
      clindamycin, an alternative agent for intrapartum prophylaxis. Despite the
      diversity of capsular types, Ia and V were among the most common and were
      significantly associated with distinct clonal groups. In a few cases, different
      capsular types were clustered into a single clonal group, which may be related to
      capsular switching.

PMID- 23876191
TI  - Mitochondrial genome of the hydrothermal vent shrimp Nautilocaris saintlaurentae
      (Crustacea: Caridea: Alvinocarididae).
AB  - We determined the mitochondrial genome (mitogenome) of Nautilocaris
      saintlaurentae, sampled at vent fields of the Tofua Arc in the southwestern
      Pacific. The genome was 15,928 bp in length and had the typical mitogenome
      structure of the infraorder Caridea. Its protein-coding genes were very similar
      to other alvinocaridid species in respect to length, AT content, and start and
      stop codons. However, N. saintlaurentae showed a 17.4--19.2% divergence in the
      nucleotide sequence from other alvinocaridid species. This information will be
      helpful in understanding the genetic relationship among members of the
      alvinocaridid shrimps. 

PMID- 23876190
TI  - HIV-associated lung cancer: survival in an unselected cohort.
AB  - BACKGROUND: Lung cancer is one of the most common non-AIDS-defining malignancies
      in HIV-infected patients. However, data on clinical outcome and prognostic
      factors are scarce. METHODS: This was a national German multicentre,
      retrospective cohort analysis of all cases of lung cancer seen in HIV-infected
      individuals from 2000 through 2010. Survival was analyzed with respect to the use
      of antiretroviral therapy (ART), specific lung cancer therapies, and other
      potential prognostic factors. RESULTS: A total of 72 patients (mean age 55.5 y,
      CD4 T-cells 383/MUl) were evaluated in this analysis. At time of lung cancer
      diagnosis, 86% were on ART. Of these, 79% had undetectable HIV-1 RNA (< 50
      copies/ml) for a mean duration of 4.0 y. All but 1 patient were current or former
      heavy smokers (mean 42 package y). The median estimated overall survival was 1.08
      y, with a 2-y overall survival of 24%. The prognosis did not improve during the
      observation time. A limited lung cancer stage of I-IIIA was associated with
      better overall survival when compared with the advanced stages IIIb/IV (p =
      0.0003). Other factors predictive of improved overall survival were better
      performance status, CD4 T-cells > 200/MUl, and a non-intravenous drug use
      transmission risk for HIV. CONCLUSIONS: Currently, most cases of lung cancer
      occur in the setting of limited immune deficiency and a long-lasting viral
      suppression. As in HIV-negative cases, the clinical stage of lung cancer is
      highly predictive of survival, and long-term overall survival can only be
      achieved at the limited stages. The still high mortality underscores the
      importance of smoking cessation strategies in HIV-infected patients.

PMID- 23876192
TI  - Phylogenetic analysis of Pomacea canaliculata isolates collected from rice fields
      in different origins of China by combined mitochondrial 12S and 16S genes.
AB  - To study the genetic relationships of Pomacea canaliculata collected from rice
      fields in China, the mitochondrial (mt) 12S and 16S of 9 P. canaliculata isolates
      from 5 southern provinces in China were sequenced and analyzed. The intra
      specific sequence variations of P. canaliculata were 0-1.1% for 12S and 0--0.6%
      for 16S, while the inter-specific variations among common Pomacea species in mt
      12S and 16S were 3.0-11.7% and 2.3-10.1%, respectively. Phylogenetic analysis
      based on combined sequences of mt 12S and 16S revealed complex genetic structure
      of P. canaliculata in China. Two phylogenetic groups of P. canaliculata were
      indicated in China with one group sistered to P. canaliculata isolates from USA,
      and two groups were even found in the same province. The phylogenetic
      relationships of Pomacea spp. also could be effectively inferred by combined
      sequences of mt 12S and 16S. These findings provided basic information for
      further study of population genetics and diffusion pattern of P. canaliculata in
      China as well as in the world. 

PMID- 23876193
TI  - Psychosocial factors associated with suicidal ideation in clinical patients with
      depression.
AB  - BACKGROUND: Depression is a major risk factor for suicide, but few studies have
      examined psychosocial risk factors for suicide in clinical patients with
      depression. The purpose of this study was to investigate psychosocial factors
      which could be associated with suicidal ideation in clinical patients with
      depression including: sick-leave, help-seeking behavior, and reluctance to admit
      mental health problems. METHODS: A multi-center cross-sectional survey using self
      report questionnaire was conducted at 54 outpatient psychiatric clinics in Tokyo
      in 2012. Adult outpatients who were diagnosed by psychiatrists as mood disorders
      (F30-F39) in the International Classification of Diseases-10 (ICD-10) were
      included in the study. Those who met the criteria for current hypomanic or manic
      episode were excluded from the study. RESULTS: A total of 189 patients with
      depression participated in the survey. Multivariable logistic regression analysis
      showed that taking sick-leave and having sought help from family were associated
      with decreased odds of current suicidal ideation. Moderate or more severe
      depression was associated with increased odds of suicidal ideation, and
      reluctance to admit own mental health problem tended to increase odds of suicidal
      ideation. LIMITATIONS: Living status and suicidal ideation before consultation
      with psychiatrist were not investigated. Severity of suicidal ideation and
      comorbid psychiatric disorders were not assessed. CONCLUSIONS: Importance of
      treatment of more severe depression for suicide prevention was confirmed.
      Industrial health staffs should consider the possibility of positive effect of
      taking sick-leave when they see employees with depression. Promoting help-seeking
      for family and reducing stigma of mental illness may be effective for suicide
      prevention.

PMID- 23876194
TI  - What is the association between quality of treatment for depression and patient
      outcomes? A cohort study of adults consulting in primary care.
AB  - BACKGROUND: The association between adequate treatment for a Major Depressive
      Episode (MDE) and improvements in depressive symptoms is not well established in
      naturalistic practice conditions. The main objective of this study was to examine
      the association between receiving at least one minimally adequate treatment for
      MDE (i.e. according to clinical guidelines) in the previous 12 months and
      evolution of depressive symptoms at 6- and 12-months. Associations with receiving
      pharmacotherapy and/or psychotherapy and the role of severity of depression were
      examined. METHODS: This cohort study included 908 adults meeting criteria for
      previous-year MDE and consulting at one of 65 primary care clinics in Quebec,
      Canada. Multilevel analyses were performed. RESULTS: Results show that (i)
      receiving at least one minimally adequate treatment for depression was associated
      with greater improvements in depression symptoms at 6 and at 12 months; (ii)
      adequate pharmacotherapy and adequate psychotherapy were both associated with
      greater improvements in depression symptoms, and (iii) the association between
      adequate treatment and improvement in depression symptoms varied as a function of
      severity of symptoms at the time of inclusion in the cohort with worse symptoms
      at the time of inclusion being associated with greater reductions at 6 and 12
      months. LIMITATIONS: Measures are self-reported. Participants were recruited at
      different stages over the course of their MDE. CONCLUSIONS: This study shows that
      adequate treatment for depression is associated with improvements in depressive
      symptoms in naturalistic primary care practice conditions, but that those with
      more severe depressive symptoms are more likely to receive adequate treatment and
      improve across time.

PMID- 23876195
TI  - Distinct alterations in value-based decision-making and cognitive control in
      suicide attempters: toward a dual neurocognitive model.
AB  - OBJECTIVE: The literature suggests that many suicide attempters show impairment
      in both decision-making and cognitive control. However, it is not clear if these
      deficits are linked to each other, and if they may be related to more basic
      alterations in attention. This is a relevant question in the perspective of
      future interventions targeting cognitive deficits to prevent suicidal acts.
      METHOD: Two different populations of patients with histories of suicide attempts
      were assessed (N=142 and 119). The Iowa Gambling Task (IGT) was used to measure
      decision-making in both populations. We used a D2 cancellation task and a verbal
      working memory task in population 1; the Stroop test, the N-Back task, the Trail
      Making Test, and the Hayling Sentence Completion test in population 2. RESULTS:
      Regarding decision-making, we only found a small negative correlation between the
      Hayling test error score (r=-0.24; p=0.01), and the net score from the second
      half of the IGT. In contrast, working memory, cognitive flexibility and cognitive
      inhibition measures were largely inter-correlated. LIMITATION: Most patients were
      medicated. Only patients with mood disorders. CONCLUSION: These results add to
      previous findings suggesting that the neurocognitive vulnerability to suicidal
      behavior may rely on impairments in two distinct anatomical systems, one
      processing value-based decision-making (associated with ventral prefrontal
      cortex, among others) and one underlying cognitive control (associated with more
      dorsal prefrontal regions). This distinction may result in tailored-made
      cognitive interventions.

PMID- 23876197
TI  - Inhomogeneous sparseness leads to dynamic instability during sequence memory
      recall in a recurrent neural network model.
AB  - Theoretical models of associative memory generally assume most of their
      parameters to be homogeneous across the network. Conversely, biological neural
      networks exhibit high variability of structural as well as activity parameters.
      In this paper, we extend the classical clipped learning rule by Willshaw to
      networks with inhomogeneous sparseness, i.e., the number of active neurons may
      vary across memory items. We evaluate this learning rule for sequence memory
      networks with instantaneous feedback inhibition and show that little
      surprisingly, memory capacity degrades with increased variability in sparseness.
      The loss of capacity, however, is very small for short sequences of less than
      about 10 associations. Most interestingly, we further show that, due to feedback
      inhibition, too large patterns are much less detrimental for memory capacity than
      too small patterns. 

PMID- 23876198
TI  - Chevron nails: a normal variant in the pediatric population.
AB  - A 7-month-old girl was evaluated for V-shaped ridging of the fingernails
      consistent with chevron nails. Chevron nails are a normal variant in the
      pediatric population that is frequently outgrown. This case nicely demonstrates
      this normal finding that has so rarely been reported in the literature.

PMID- 23876199
TI  - Guillain-Barre syndrome: natural history and prognostic factors: a retrospective
      review of 106 cases.
AB  - BACKGROUND: Guillain-Barre syndrome (GBS) is characterized by acute onset and
      progressive course, and is usually associated with a good prognosis. However,
      there are forms of poor prognosis, needing ventilatory support and major deficits
      at discharge. With this study we try to identify the factors associated with a
      worse outcome. METHODS: 106 cases of GBS admitted in our hospital between years
      2000-2010 were reviewed. Epidemiological, clinical, therapeutical and
      evolutionary data were collected. RESULTS: At admission 45% had severe deficits,
      percentage which improves throughout the evolution of the illness, with full
      recovery or minor deficits in the 87% of patients at the first year review. Ages
      greater than 55 years, severity at admission (p < 0.001), injured cranial nerves
      (p = 0.008) and the needing of ventilator support (p = 0.003) were associated
      with greater sequels at the discharge and at the posterior reviews in the
      following months. 17% required mechanical ventilation (MV). Values < 250 L/min in
      the Peak Flow-test are associated with an increased likelihood of requiring MV (p
      < 0.001). CONCLUSIONS: Older age, severe deficits at onset, injured cranial
      nerves, requiring MV, and axonal lesion patterns in the NCS were demonstrated as
      poor prognostic factors. Peak Flow-test is a useful predictive factor of
      respiratory failure by its easy management.

PMID- 23876200
TI  - Tunable plasticity in amorphous silicon carbide films.
AB  - Plasticity plays a crucial role in the mechanical behavior of engineering
      materials. For instance, energy dissipation during plastic deformation is vital
      to the sufficient fracture resistance of engineering materials. Thus, the lack of
      plasticity in brittle hybrid organic-inorganic glasses (hybrid glasses) often
      results in a low fracture resistance and has been a significant challenge for
      their integration and applications. Here, we demonstrate that hydrogenated
      amorphous silicon carbide films, a class of hybrid glasses, can exhibit a
      plasticity that is even tunable by controlling their molecular structure and
      thereby leads to an increased and adjustable fracture resistance in the films. We
      decouple the plasticity contribution from the fracture resistance of the films by
      estimating the "work-of-fracture" using a mean-field approach, which provides
      some insight into a potential connection between the onset of plasticity in the
      films and the well-known rigidity percolation threshold. 

PMID- 23876201
TI  - [Saccharomyces cerevisiae fungemia in a premature neonate treated receiving
      probiotics].

PMID- 23876202
TI  - Hospital cross-transmission of extended-spectrum beta-lactamase producing
      Escherichia coli and Klebsiella pneumoniae.
AB  - OBJECTIVES: We had for objective to measure the incidence and the clonal
      diversity of Escherichia coli and Klebsiella pneumoniae producing extended
      spectrum beta-lactamases (ESBL) in order to assess the role of patient stay in
      amplification of the phenomenon, in our teaching hospital. MATERIAL AND METHODS:
      We measured the quarterly incidence rates of E. coli and K. pneumoniae producing
      or not producing ESBL in clinical samples between 1999 and 2010. The incidence of
      ESBL-producing isolates was season-adjusted. We determined the pulsotype of and
      identified the ESBL in all non-redundant strains isolated between 2009 and 2010.
      RESULTS: The incidence for 1000 hospitalization days increased from 0.00 to 0.44
      for ESBL-producing E. coli, from 0.012 to 0.24 for ESBL-producing K. pneumoniae,
      from 1999 to 2010. Fifty-three different clones of E. coli were identified among
      the 61 genotyped isolates. The 28 K. pneumoniae isolates genotyped clustered into
      11 different clones, among which one major epidemic clone that included 18
      isolates. Respectively 66 and 75% of E. coli and K. pneumoniae isolates produced
      a CTX-M group 1 ESBL. CONCLUSION: The hospital seems to play a different role in
      the amplification of ESBL according to the producing species (K. pneumoniae or E.
      coli). ESBL-producing E. coli seem to have a limited cross-transmission within
      the hospital and seem to be added to non-producers. Conversely, ESBL-producing K.
      pneumoniae seem to be cross-transmitted within the hospital and to replace non
      producers.

PMID- 23876203
TI  - Prospective follow-up of complications related to peripherally inserted central
      catheters.
AB  - An increased use of peripherally inserted central catheters (PICC) in French
      hospitals has been observed in recent years. We report complications having
      occurred following the placement of PICC in a teaching hospital. PATIENTS AND
      METHODS: A prospective study was made for 7 months, between October 2010 and
      April 2011, including all patients having undergone PICC placement in
      interventional radiology. RESULTS: Two hundred and sixty-seven PICC were inserted
      in 222 patients for intravenous antibiotic therapy (68%), parenteral nutrition
      (13%), or chemotherapy (9%). The median duration of PICC use was 17 days (min
      max: 1-140) for the 200 PICC monitored until removal. The most common
      complication was obstruction (n=41), 16 of which motivated PICC removal (8%).
      Five cases of vein thrombosis (2.5%) and 20 infectious complications (10%) led to
      removal. There were 14 accidental removals (7%). The overall infection rate was
      2.3 per 1000 catheter-days with 0.86 per 1000 catheter-days for central line
      associated bloodstream infection. Thirty-four percent of PICC were removed
      without any complications without any difference according to use. CONCLUSION:
      PICC are a simple alternative to standard central venous catheter but the rate of
      complications is high and could be decreased by a stringent management and
      training for this type of catheter.

PMID- 23876204
TI  - Evolution of hepatitis B vaccine coverage rates in France between 2008 and 2011.
AB  - High vaccine coverage rates were reached for hepatitis B vaccination in teenagers
      nearly two decades ago (1995), but controversy sharply decreased the rate of
      vaccination in France, requiring high remobilization in its favor and careful
      monitoring of vaccine coverage rates. We report the results of Vaccinoscopie((r))
      survey which has monitored the yearly evolution of vaccine coverage rates since
      2008. METHOD: A representative national sample of 5250 mothers was recruited in
      2011: 3000 mothers of infants (1000 for each of the following age range: 0-11
      months, 12-23 months, and 24-35 months of age) and 2250 mothers of teenagers.
      They all answered a self-administered questionnaire on the Internet and reported
      all vaccinations included in their child's health record. RESULTS: In 2011, 82.4%
      (CI 95%: 77.6-87.1) of infants 6-8 months of age were given hepatitis B
      vaccination before six months of age and 71.9% (CI 95%: 66.3-77.5) of children 24
      26 months of age were fully immunized before 24 months of age. France should
      reach its objectives for infants thanks to the hexavalent vaccine, but this is
      not the case for teenagers since in 2011, at 14-16 years of age, only 55.4% (CI
      95%: 53.3-57.4) had started their vaccination schedule and 37.4% (CI 95%: 35.4
      39.4) were fully vaccinated. CONCLUSION: This recent data, specially concerning
      teenagers, should lead to corrective measures rapidly to reach vaccine coverage
      targets for this vaccination.

PMID- 23876205
TI  - Cutaneous tuberculosis in Tunisia.
AB  - INTRODUCTION: Tuberculosis is endemic in Tunisia. Pulmonary tuberculosis is the
      most common presentation in our country. Cutaneous presentations are rare (1-2%
      of cases). The diagnosis of cutaneous tuberculosis (CT) is difficult.
      Histological and clinical presentations are polymorphous, many differential
      diagnoses are available, and it is difficult to isolate Mycobacterium. OBJECTIVE:
      We had for aim to study the epidemiological and clinical features of CT in
      Tunisia, and to compare presentations before and after 1990. PATIENTS AND
      METHODS: We conducted a retrospective study between January 1991 and December
      2011, in which we included all cases of CT observed at the Infectious Diseases
      and Dermatology Units of the Tunis la Rabta Hospital. RESULTS: Hundred and thirty
      seven patients were included, with a mean age of 43.8years; 72.3% were female
      patients. Hundred and fifty locations were observed, most of which on the head
      and neck. Scrofuloderma was the most frequent presentation, observed in 65% of
      cases. The diagnosis was confirmed by histology and/or microbiology in 75.8% of
      cases. The treatment was prescribed for a mean 11.3months, leading to full
      recovery in most cases. CONCLUSION: CT is still reported in Tunisia. The
      diagnosis relies mainly on histology. Controlling this mutilating tuberculosis
      requires a global control of this disease, and especially lymph node location,
      given the high rate of scrofuloderma.

PMID- 23876206
TI  - Genetic diversity of influenza B virus in 2009-2010 and 2010-2011 in Tunisia.
AB  - OBJECTIVE: The authors had for aim to characterize influenza B strains having
      circulated in Tunisia to identify new mutations and compare them with reference
      strains. METHODS: The epidemiological surveillance of influenza allowed
      identifying 19 patients with symptoms related to respiratory infection, who had
      been infected by influenza B strains isolated in several regions of Tunisia in
      2009-2010 and in 2010-2011. Laboratory identification and detection of mutations
      in the segment encoding hemagglutinin of influenza viruses was performed by real
      time PCR and sequencing. RESULTS: The two influenza B Tunisian strains of the
      2009-2010 season belonged to the Victoria lineage, whereas 2010-2011 season
      strains belonged to B/Victoria/2/87 and B/Yamagata/16/88 lineages with a
      dominance of the Yamagata lineage (76%). This study allowed identifying amino
      acid substitutions: T121A, S150I, N165Y, T181A, G183R, D196N, S229D, M251V and
      K253R in the B/Yamagata lineage; L58P, N75K, K109N, N165K, S172P and K257R into
      the B/Victoria lineage. These mutations were specific of Tunisian groups of
      variants. Most influenza B-Yamagata lineage viruses (69%) were associated with
      severe cases. CONCLUSION: Molecular analysis of the various influenza B strains
      circulating in Tunisia is useful to detect new mutations that can modify the
      phenotype of influenza strains.

PMID- 23876207
TI  - [BK or not BK? A misleading presentation].

PMID- 23876208
TI  - Broad-range PCR: past, present, or future of bacteriology?
AB  - PCR targeting the gene encoding 16S ribosomal RNA (commonly named broad-range PCR
      or 16S PCR) has been used for 20 years as a polyvalent tool to study prokaryotes.
      Broad-range PCR was first used as a taxonomic tool, then in clinical
      microbiology. We will describe the use of broad-range PCR in clinical
      microbiology. The first application was identification of bacterial strains
      obtained by culture but whose phenotypic or proteomic identification remained
      difficult or impossible. This changed bacterial taxonomy and allowed discovering
      many new species. The second application of broad-range PCR in clinical
      microbiology is the detection of bacterial DNA from clinical samples; we will
      review the clinical settings in which the technique proved useful (such as
      endocarditis) and those in which it did not (such as characterization of bacteria
      in ascites, in cirrhotic patients). This technique allowed identifying the
      etiological agents for several diseases, such as Whipple disease. This review is
      a synthesis of data concerning the applications, assets, and drawbacks of broad
      range PCR in clinical microbiology.

PMID- 23876209
TI  - Change of mammographic density predicts the risk of contralateral breast cancer-
      a case-control study.
AB  - INTRODUCTION: Mammographic density is a strong risk factor for breast cancer, but
      it is unknown whether density at first breast cancer diagnosis and changes during
      follow-up influences risk of non-simultaneous contralateral breast cancer (CBC).
      METHODS: We collected mammograms for CBC-patients (cases, N = 211) and unilateral
      breast cancer patients (controls, N = 211), individually matched on age and
      calendar period of first breast cancer diagnosis, type of adjuvant therapy and
      length of follow-up (mean follow-up time: 8.25 years). The odds of CBC as a
      function of changes of density during follow-up were investigated using
      conditional logistic regression, adjusting for non-dense area at diagnosis.
      RESULTS: Patients who experienced >=10% absolute decrease in percent density had
      a 55% decreased odds of CBC (OR = 0.45 95% CI: 0.24 to 0.84) relative to patients
      who had little or no change in density from baseline to first follow-up mammogram
      (mean = 1.6 (SD = 0.6) years after diagnosis), whereas among those who
      experienced an absolute increase in percent density we could not detect any
      effect on the odds of CBC (OR = 0.83 95% CI: 0.24 to 2.87). CONCLUSION: Decrease
      of mammographic density within the first two years after first diagnosis is
      associated with a significantly reduced risk of CBC, this potential new risk
      predictor can thus contribute to decision-making in follow-up strategies and
      treatment.

PMID- 23876210
TI  - Efficacy and safety of entecavir treatment in a heterogeneous CHB population from
      a 'real-world' clinical practice setting in China.
AB  - Chronic hepatitis B infection is an important cause of liver-related mortality in
      China. This study assessed the efficacy and safety of entecavir in a
      heterogeneous patient population from a 'real-world' clinical practice setting in
      China. This prospective, observational cohort provides 48-week data on 2600
      patients from 50 sites in China who received entecavir (0.5 or 1.0 mg) and were
      assessed for virologic, serologic and biochemical responses. Patients were
      nucleos(t)ide-na?ive or -experienced and had compensated or decompensated liver
      function. At Week 48, 1545/2424 (64%) patients with compensated liver disease and
      30/44 (68%) patients with decompensated liver disease achieved HBV DNA<50 IU/mL.
      Greater proportions of nucleos(t)ide-na?ive than nucleos(t)ide-experienced (69%
      vs 53%), and adefovir-experienced than lamivudine/ telbivudine-experienced (62%
      vs 52%) patients achieved this endpoint. Most patients with HBV DNA<50 IU/mL also
      achieved HBV DNA<12 IU/L (60%, 45% and 61% of nucleos(t)ide-na?ive, nucleos(t)ide
      experienced and decompensated patients, respectively). In patients with
      compensated liver disease, ALT values normalized in 1532/1792 patients (85%), and
      HBeAg loss and HBeAg seroconversion were observed in 17% and 15% of treatment
      na?ive and 15% and 11% of treatment-experienced patients. Entecavir was generally
      well tolerated. Adverse event rates were comparable between treatment-na?ive and
      treatment-experienced patients with compensated liver disease, but were higher in
      decompensated than in compensated patients, consistent with previous reports in
      these patients with more advanced disease. Four patients discontinued treatment
      due to adverse events. In a 'real-world' setting, entecavir was efficacious and
      well tolerated throughout 48 weeks in a heterogeneous Chinese CHB population.

PMID- 23876211
TI  - Effects of angiotensin II type 1 receptor blocker and adiponectin on adipocyte
      dysfunction in stroke-prone spontaneously hypertensive rats.
AB  - BACKGROUND: Hypoadiponectinemia in lipoatrophy may be related to worsening of
      hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). One of the
      beneficial effects of candesartan (Angiotensin II Type 1 receptor blocker) for
      preventing hypertension may be increasing of adiponectin due to improvement of
      adipocyte dysfunction. In this study, we determined the effects of candesartan or
      adiponectin on pathophysiologic features and adipocyte dysfunction in SHRSP.
      METHODS: Candesartan was administered to male SHRSP from 16 to 20 weeks of age (2
      mg/kg/day). Adiponectin was cloned and intravenously administered to male SHRSP
      from 16 to 20 weeks of age. We examined biological parameters, as well as the
      expression and release of adipokines. RESULTS: The SHRSP exhibited severe atrophy
      of visceral fat and progression of severe hypertension. The expression and
      release of leptin and adiponectin were impaired at 6 and 20 weeks of age.
      Candesartan suppressed the development of lipoatrophy and reduced the incidence
      of stroke at 20 weeks of age. Candesartan also enhanced the expression of
      adiponectin and leptin by inducing the overexpression of peroxisome proliferator
      activated receptor gamma. Circulating level of leptin was significantly higher in
      candesartan group than in the control group, whereas adiponectin was similar in
      both groups. Intravenous administration of adiponectin resulted in enhancement of
      adiponectin expression in adipose tissue, but no remarkable effects were found in
      pathophysiology in SHRSP. CONCLUSIONS: Our results indicate that candesartan
      protects against hypertension and adipocyte dysfunction in SHRSP. The induction
      of leptin expression appeared to be important factor in the inhibition of stroke
      lesions, whereas adiponectin was not a major regulator of blood pressure in SHRSP
      with genetic hypertension. Further studies are needed to elucidate the role of
      the renin-angiotensin system in adipose tissue dysfunction in relation to
      hypertensive end-organ damage.

PMID- 23876212
TI  - Psychometric properties of the self-efficacy for clinical evaluation scale in
      Turkish nursing students.
AB  - AIMS AND OBJECTIVES: To examine psychometric properties of the Self-Efficacy for
      Clinical Evaluation Scale (SECS) in a nursing student sample. BACKGROUND: Self
      efficacy is a good choice to be used in order to make a prediction of nursing
      students' performance in clinical practice. The SECS, consisting of perceived
      self-efficacy and importance subscales, seems to be suitable to evaluate self
      efficacy regarding care skills for patients with chronic diseases. However, there
      is not a valid tool to evaluate the perception of self-efficacy for Turkish
      nursing students. DESIGN: Cross-sectional methodological design. METHODS: The
      sample included 400 Turkish nursing students who attended practicum at a
      hospital. Content of the SECS was evaluated by content validity index (CVI).
      Reliability was evaluated with internal consistency, item-total correlation and
      test-retest reliability. Confirmatory factor analysis (CFA) and convergent and
      divergent validity were used to test the validity. RESULTS: The CVI results were
      satisfactory. We found satisfactory evidence for internal consistency and item
      total correlations. Intraclass correlation coefficients showed stability of
      subscales. The CFA replicated two-factor structure for the SECS. This was
      reflected in all fit indices. All factor loadings were positive and were above
      the perfect level. The convergent validity was supported by the correlation
      between SECS and General Self-Efficacy Scale. The divergent validity findings
      demonstrated that SECS differentiated between students with various levels of
      general point average, which is an indicator of academic success. CONCLUSION: In
      conclusion, SECS is a reliable and valid tool used in clinical nursing education
      settings. RELEVANCE TO CLINICAL PRACTICE: Measuring students' self-efficacy in a
      clinical environment can provide an insight for students into what they have
      learned. Nurse educators can also use the SECS to spot nursing students with
      weaknesses in care activities and create educational strategies to help them to
      enhance their academic performance. Using the SECS can yield an insight both for
      students and for nursing educators.

PMID- 23876213
TI  - Promotion of wound healing using adipose-derived stem cells in radiation ulcer of
      a rat model.
AB  - BACKGROUND: Wound healing is a complex biologic process that involves the
      integration of inflammation, mitosis, angiogenesis, synthesis, and remodeling of
      the extracellular matrix. However, some wounds fail to heal properly and become
      chronic. Although some simulated chronic wound models have been established, an
      efficient approach to treat chronic wounds in animal models has not been
      determined. The aim of this study was to develop a modified rat model simulating
      the chronic wounds caused by clinical radiation ulcers and examine the treatment
      of chronic wounds with adipose-derived stem cells. RESULTS: Sprague-Dawley rats
      were irradiated with an electron beam, and wounds were created. The rats received
      treatment with adipose-derived stem cells (ASCs), and a wound-healing assay was
      performed. The wound sizes after ASC treatment for 3 weeks were significantly
      smaller compared with the control condition (p < 0.01). Histological observations
      of the wound edge and immunoblot analysis of the re-epithelialization region both
      indicated that the treatment with ASCs was associated with the development of new
      blood vessels. Cell-tracking experiments showed that ASCs were colocalized with
      endothelial cell markers in ulcerated tissues. CONCLUSIONS: We established a
      modified rat model of radiation-induced wounds and demonstrated that ASCs
      accelerate wound-healing.

PMID- 23876215
TI  - Etymologia: campylobacter.

PMID- 23876214
TI  - Erosive conjunctival and corneal inflammatory changes in a patient receiving
      weekly docetaxel for breast cancer.

PMID- 23876216
TI  - Clinical and oncological outcomes after surgical excision of parotid gland
      tumours in patients aged over 80 years.
AB  - The objective of this study was to evaluate the surgical and long-term outcomes
      of a series of patients aged over 80 years, operated on for parotid neoplasms.
      Among 614 parotidectomies for neoplasms performed between 1998 and 2008, 34
      patients (5.5%) aged over 80 years were identified retrospectively. Pathological
      examination showed a malignant tumour in 24 and a benign tumour in 10 cases.
      Overall survival (OS) and disease-free survival (DFS) were determined by Kaplan
      Meier analysis. A search for parameters that could influence the postoperative
      complication rate and long-term outcomes was carried out by univariate analysis.
      There was no postoperative death. Eight patients (24%) had postoperative
      complications. Malignant histopathology (P=0.05) and radical resection (P=0.033)
      were found to have a significant negative impact on the postoperative course.
      Focusing on malignant tumours, only histopathological type (metastasis vs primary
      tumour) was found to have a negative impact on OS. The 2- and 5-year OS rates
      were 86% and 86%, respectively, for primary tumours, and 67% and 29%,
      respectively, for metastasis (P=0.05). Malignant or benign histopathology had no
      impact on OS. Our results showed acceptable clinical and long-term oncological
      outcomes in very elderly patients operated on for parotid tumours, including
      malignant tumours. 

PMID- 23876196
TI  - Suicidal ideation in a European Huntington's disease population.
AB  - BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation,
      suicide attempts, and completed suicide in Huntington's disease (HD) compared
      with the general population. This study investigates correlates and predictors of
      suicidal ideation in HD. METHODS: The study cohort consisted of 2106 HD mutation
      carriers, all participating in the REGISTRY study of the European Huntington's
      Disease Network. Of the 1937 participants without suicidal ideation at baseline,
      945 had one or more follow-up measurements. Participants were assessed for
      suicidal ideation by the behavioural subscale of the Unified Huntington's Disease
      Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using
      logistic regression analysis and predictors were analyzed using Cox regression
      analysis. RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal
      ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]:
      0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5
      3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood
      (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at
      baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%.
      Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI:
      1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were
      independent predictors of incident suicidal ideation, whereas a previous suicide
      attempt was not predictive. LIMITATIONS: As suicidal ideation was assessed by
      only one item, and participants were a selection of all HD mutation carriers, the
      prevalence of suicidal ideation was likely underestimated. CONCLUSIONS: Suicidal
      ideation in HD frequently occurs. Assessment of suicidal ideation is a priority
      in mutation carriers with a depressed mood and in those using benzodiazepines.

PMID- 23876217
TI  - The 5'-untranslated region regulates ATF5 mRNA stability via nonsense-mediated
      mRNA decay in response to environmental stress.
AB  - We previously reported that activating transcription factor 5 (ATF5) mRNA
      increases in response to amino acid limitation, and that this increase is
      dependent on mRNA stabilization. The ATF5 gene allows transcription of mRNAs with
      two alternative 5'-UTRs, 5'-UTRalpha and 5'-UTRbeta, derived from exon 1alpha and
      exon 1beta. 5'-UTRalpha contains the upstream open reading frames uORF1 and
      uORF2. Phosphorylation of eukaryotic initiation factor 2alpha during the
      integrated stress response had been previously shown to lead to bypassing of
      uORF2 translation and production of ATF5 protein. Translation of uORF2 is
      expected to result in translational termination at a position 125 nucleotides
      upstream of the exon junction, and this fits the criterion of a nonsense-mediated
      decay target mRNA. We investigated the potential role of 5'-UTRalpha in the
      control of mRNA stabilization, and found that 5'-UTRalpha reduced the stability
      of ATF5 mRNA. 5'-UTRalpha-regulated destabilization of mRNA was suppressed by
      knockdown of the nonsense-mediated decay factors Upf1 and Upf2. Mutation of the
      downstream AUG (uAUG2) rendered mRNA refractory to Upf1 and Upf2 knockdown.
      Moreover, 5'-UTRalpha-regulated down-regulation was hindered by amino acid
      limitation and tunicamycin treatment, and stress-induced phosphorylation of
      eukaryotic initiation factor 2alpha was involved in stabilization of ATF5 mRNA.
      These studies show that ATF5 mRNA is a naturally occurring normal mRNA target of
      nonsense-mediated decay, and provide evidence for linkage between stress
      regulated translational regulation and the mRNA decay pathway. This linkage
      constitutes a mechanism that regulates expression of stress response genes.

PMID- 23876218
TI  - Illuminating the roles of the Borrelia burgdorferi adhesins.
AB  - The Lyme disease spirochetes, Borrelia burgdorferi (sensu lato), must cause
      persistent, disseminated infection to be maintained in the natural enzootic
      cycle. In human Lyme disease, spirochetes spread from the site of a tick bite to
      colonize multiple tissue sites, causing multisystem clinical manifestations. The
      Lyme spirochetes produce many adhesive surface proteins that collectively
      recognize diverse host substrates and cell types and are likely to promote
      dissemination and chronic infection in a variety of tissues. Recent application
      of state-of-the-art in vivo imaging technologies is illuminating mechanisms of
      interaction of B. burgdorferi with the host and the importance of multiple
      adhesins during mammalian infection. 

PMID- 23876219
TI  - Pretreatment and fractionation of wheat straw using various ionic liquids.
AB  - Pretreatment of lignocellulosic biomass with ionic liquids (ILs) is a promising
      and challenging process for an alternative method of biomass processing. The
      present work emphasizes the examination of wheat straw pretreatment using ILs,
      namely, 1-butyl-3-methylimidazolium hydrogensulfate ([bmim][HSO4]), 1-butyl-3
      methylimidazolium thiocyanate ([bmim][SCN]), and 1-butyl-3-methylimidazolium
      dicyanamide ([bmim][N(CN)2]). Only [bmim][HSO4] was found to achieve a
      macroscopic complete dissolution of wheat straw during pretreatment. The
      fractionation process demonstrated to be dependent on the IL used. Using
      [bmim][SCN], a high-purity lignin-rich material was obtained. In contrast,
      [bmim][N(CN)2] was a good solvent to produce high-purity carbohydrate-rich
      fractions. When [bmim][HSO4] was used, a different behavior was observed,
      exhibiting similarities to an acid hydrolysis pretreatment, and no hemicellulose
      rich material was recovered during fractionation. A capillary electrophoresis
      (CE) technique allowed for a better understanding of this phenomenon. Hydrolysis
      of carbohydrates was confirmed, although an extended degradation of
      monosaccharides to furfural and hydroxymethylfurfural (HMF) was observed. 

PMID- 23876220
TI  - Epilepsy and homicide: beware of the EEG (a misdiagnosis can occur!).

PMID- 23876221
TI  - Clinical review: Continuous and simplified electroencephalography to monitor
      brain recovery after cardiac arrest.
AB  - There has been a dramatic change in hospital care of cardiac arrest survivors in
      recent years, including the use of target temperature management (hypothermia).
      Clinical signs of recovery or deterioration, which previously could be observed,
      are now concealed by sedation, analgesia, and muscle paralysis. Seizures are
      common after cardiac arrest, but few centers can offer high-quality
      electroencephalography (EEG) monitoring around the clock. This is due primarily
      to its complexity and lack of resources but also to uncertainty regarding the
      clinical value of monitoring EEG and of treating post-ischemic electrographic
      seizures. Thanks to technical advances in recent years, EEG monitoring has become
      more available. Large amounts of EEG data can be linked within a hospital or
      between neighboring hospitals for expert opinion. Continuous EEG (cEEG)
      monitoring provides dynamic information and can be used to assess the evolution
      of EEG patterns and to detect seizures. cEEG can be made more simple by reducing
      the number of electrodes and by adding trend analysis to the original EEG curves.
      In our version of simplified cEEG, we combine a reduced montage, displaying two
      channels of the original EEG, with amplitude-integrated EEG trend curves (aEEG).
      This is a convenient method to monitor cerebral function in comatose patients
      after cardiac arrest but has yet to be validated against the gold standard, a
      multichannel cEEG. We recently proposed a simplified system for interpreting EEG
      rhythms after cardiac arrest, defining four major EEG patterns. In this topical
      review, we will discuss cEEG to monitor brain function after cardiac arrest in
      general and how a simplified cEEG, with a reduced number of electrodes and trend
      analysis, may facilitate and improve care. 

PMID- 23876222
TI  - Treatment of preadolescent acne in the United States: an analysis of nationally
      representative data.
AB  - The prevalence of acne in younger children is increasing. Of the acne treatments
      that the U.S. Food and Drug Administration (FDA) has approved for ages 12 years
      and older, it is unclear which medications are being prescribed off-label for
      this younger patient population. The purpose of this study is to compare the
      therapies being prescribed to preadolescent patients with acne (defined in this
      study as ages 7 to 11 years) with those being prescribed to adolescent patients
      (ages 12 to 18 years) and to determine whether prescribing patterns differ
      between dermatologists and pediatricians. Leading therapies for the treatment of
      children with a diagnosis of acne were collected from the National Ambulatory
      Medical Care Survey (NAMCS) from 1993 to 2009. Data were stratified according to
      age group and physician specialty. Physicians prescribed a wide variety of FDA
      approved and off-label medications to preadolescent patients with acne. The
      leading medications were topical treatments, including adapalene (14.4%), benzoyl
      peroxide (12.8%), and tretinoin (12.5%). Treatment of this age group differed
      substantially between specialties, with dermatologists frequently prescribing
      topical retinoids and primary care physicians preferring antibiotics,
      particularly oral antibiotics. Limitations included a lack of data on acne
      severity and morphology through NAMCS, as well as the absence of longitudinal
      data. With the limited number of FDA-approved treatment options, off-label
      prescribing for acne in preadolescent patients is common. Furthermore, this study
      identified a potential knowledge gap between pediatricians based on their
      prescribing patterns in this patient population. 

PMID- 23876223
TI  - Evolution of life expectancy of patients with Duchenne muscular dystrophy at AFM
      Yolaine de Kepper centre between 1981 and 2011.
AB  - OBJECTIVES: Retrospective study over the last 30 years of life expectancy in
      patients suffering from Duchenne muscular dystrophy (DMD). Analysis of the role
      of ventilatory assistance and causes of death. PATIENTS AND METHODS: One hundred
      and nineteen adult DMD patients were hosted during 1981 to 2011 at AFM Yolaine de
      Kepper centre, Saint-Georges-sur-Loire, France. Patients' life expectancy was
      calculated using Kaplan-Meier model. RESULTS: Life expectancy without or with
      ventilatory assistance was 22.16 and 36.23 years, respectively. Similarly, life
      expectancy of patients born from 1970 (mostly with ventilatory assistance) was
      40.95 years old from 1970 and 25.77 years old before 1970. Causes of death
      changed. Cardiac origins of death have increased from 8% to 44%. CONCLUSION:
      Ventilator assistance, in this study mostly through tracheotomy prolongs by more
      than 15 years life expectancy of DMD patients. It allows conservation of a
      satisfactory quality of life, and should be systematically proposed to patients.

PMID- 23876224
TI  - Anti-inflammatory treatments for chronic diseases: a review.
AB  - Inflammation is viewed as one of the major causes for the development of
      different diseases like cancer, cardiovascular disease, diabetes, obesity,
      osteoporosis, rheumatoid arthritis, inflammatory bowel disease, asthma, and CNS
      related diseases such as depression and parkinson's disease; and this fervent
      phenomenon provides space for understanding different inflammatory markers.
      Increasing evidences have elucidated the outcome of inflammatory pathways
      dysregulation resulting in many symptoms of chronic diseases. The detection of
      transcription factors such as nuclear factor kappa-B (NF-kappaB), STAT and their
      gene products such as COX-2, cytokines, chemokines and chemokine receptors has
      laid molecular foundation for the important role of inflammation in chronic
      diseases in which the NF-kappaB is reported as a major mediator which makes a
      possible way for the development of new therapeutic approaches using synthetic
      and natural compounds that might eventually decrease the prevalence of these
      diseases. Even if many inflammatory markers like TNF-alpha, IL-1, IL-6, IL-8 and
      C-reactive protein (CRP) are reported to be the major key factors with proved
      role in several inflammatory diseases, IL-1 and TNF-alpha are the important
      cytokines that can induce the expression of NF-kappaB which is the potential
      target in these inflammatory diseases. This review aims to explore and summarize
      that how some drugs and natural compounds show their modulatory activity in
      inflammatory pathways and chronic inflammatory markers in these inflammatory
      diseases. 

PMID- 23876225
TI  - Enhancing the tensile properties of continuous millimeter-scale carbon nanotube
      fibers by densification.
AB  - This work presents a study of the tensile mechanical properties of millimeter
      long fibers comprising carbon nanotubes (CNTs). These CNT fibers are made of
      aligned, loosely packed parallel networks of CNTs that are grown in and harvested
      from CNT forests without drawing or spinning. Unlike typical CNT yarn, the
      present fibers contain a large fraction of CNTs that span the fibers' entire
      gauge length. The fibers are densified after growth and network formation to
      study how increasing the degree of interaction among CNTs in a network by various
      methods influences and limits the mechanical behavior of macroscopic CNT
      materials, particularly for the case in which the continuity of a large fraction
      of CNTs across the gauge length prevents failure purely by slip. Densification is
      carried out using various combinations of capillary-driven densification,
      mechanical pressure, and twisting. All methods of densification increase the
      fiber density and modify the nanoscale order of the CNTs. The highest strength
      and stiffness values (1.8 and 88.7 N tex(-1), respectively) are observed for
      capillary-densified fibers, whereas the highest toughness values (94 J g(-1)) and
      maximum reversible energy density (1.35 kJ kg(-1) or 677 kJ m(-3)) are observed
      for fibers densified by mechanical pressure. The results suggest that the path to
      higher performance CNT materials may lie not only in the use of continuous and
      long CNTs but also in controlling their density and nanoscale ordering through
      modification of the as-grown networks, such as by capillary-driven densification.

PMID- 23876226
TI  - Unnecessary injecting of medicines is still a major public health challenge
      globally.

PMID- 23876227
TI  - Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte
      ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy.
AB  - BACKGROUND: Several inflammatory response materials could be used for prediction
      of prognosis of cancer patients. The neutrophil lymphocyte ratio (NLR), and the
      platelet lymphocyte ratio (PLR) have been introduced for prognostic scoring
      system in various cancers. The objective of this study was to determine whether
      the NLR or the PLR would predict the clinical outcomes in advanced gastric cancer
      patients treated with oxaliplatin/ 5-fluorouracil (FOLFOX). METHODS: The study
      population consisted of 174 advanced gastric cancer patients. Patients were
      treated with 85 mg/m2 of oxaliplatin as a 2-h infusion at day 1 plus 20 mg/m2 of
      leucovorin over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous
      infusion of 600 mg/m2 at days 1-2. Treatment was repeated in 2-week intervals.
      The NLR and PLR were calculated from complete blood counts in laboratory test
      before and after first cycle of chemotherapy. RESULTS: NLR was a useful
      prognostic biomarker for predicting inferior overall survival (OS) (p = 0.005),
      but was not associated with progression free survival (PFS) (p = 0.461). The
      normalization of NLR after one cycle of chemotherapy was found to be in
      association with significant improvement in PFS (5.3 months vs. 2.4 months, p <
      0.001), and OS (11.9 months vs. 4.6 months, p < 0.001). The normalization of PLR
      was also associated with longer PFS (5.6 months vs. 3.4 months, p = 0.006), and
      OS (16.9 months vs. 10.9 months, p = 0.002). In multivariate analysis, changes in
      NLR were associated with PFS (Hazard ratio (HR): 2.297, 95% confidence interval
      (CI): 1.429-3.693, p = 0.001). The NLR, (HR: 0.245, 95% CI: 0.092-0.633, p =
      0.004), PLR (HR: 0.347, 95% CI: 0.142-0.847, p = 0.020), changes in NLR (HR:
      2.468, 95% CI: 1.567-3.886, p < 0.001), and changes in PLR (HR: 1.473, 95% CI:
      1.038-2.090, p = 0.030) were independent prognostic markers for OS. CONCLUSION:
      This study demonstrates that NLR, PLR, and changes in NLR or PLR are independent
      prognostic factor for OS in patients with advanced gastric cancer treated with
      chemotherapy. These specific factors may also help in identifying the patients,
      who are more sensitive to FOLFOX regimen.

PMID- 23876229
TI  - Eicosapentaenoic acid-enriched phospholipid ameliorates insulin resistance and
      lipid metabolism in diet-induced-obese mice.
AB  - BACKGROUND: Over the past two decades, a striking increase in the number of
      people with metabolic syndrome (MS) has taken place worldwide. With the elevated
      risk of not only diabetes but also cardiovascular morbidity and mortality, there
      is urgent need for strategies to prevent this emerging global epidemic. The
      present study was undertaken to investigate the effects of dietary
      eicosapentaenoic acid-enriched phospholipid (EPA-PL) on metabolic disorders.
      METHODS: Male C57BL/6J mice (n = 7) were fed one of the following 4 diets for a
      period of 4 weeks: 1) a modified AIN-96G diet with 5% corn oil (control diet); 2)
      a high fat (20%, wt/wt) and high fructose (20%, wt/wt) diet (HF diet); 3) the HF
      diet containing 1% SOY-PL (SOY-PL diet); 4) the HF diet containing 1% EPA-PL (EPA
      PL diet). The oral glucose tolerance test was performed. Plasma TG, TC, glucose,
      NEFA, insulin, leptin, adiponectin, TNF-alpha and IL-6 levels were assessed. In
      addition, hepatic lipid levels, lipogenic, and lipidolytic enzyme activities and
      gene expressions were evaluated. RESULTS: Both EPA-PL and SOY-PL significantly
      inhibited body weight gain and white adipose tissue accumulation, alleviated
      glucose intolerance, and lowered both serum fasting glucose and NEFA levels
      substantially. Only EPA-PL significantly reduced serum TNF-alpha and IL-6 levels,
      and increased serum adiponectin level. EPA-PL was more effective in reducing
      hepatic and serum TG and TC levels than SOY-PL. Both EPA-PL and SOY-PL reduced
      the activities of hepatic lipogenic enzymes, such as FAS and G6PDH, but only EPA
      PL significantly increased CPT, peroxisomal beta-oxidation enzymes activities and
      CPT-1a mRNA level. Alterations of hepatic lipogenic gene expressions, such as
      FAS, G6PDH, ACC, SCD-1 and SREBP-1c were consistent with changes in related
      enzyme activities. CONCLUSIONS: According to our study, EPA-PL supplementation
      was efficacious in suppressing body fat accumulation, and alleviating insulin
      resistance and hepatic steatosis by modulating the secretion of adipocytokines
      and inflammatory cytokines, suppression of SREBP-1c mediated lipogenesis and
      enhancement of fatty acid beta-oxidation. These results demonstrate that EPA-PL
      is a novel beneficial food component for the prevention and improvement of
      metabolic disorders.

PMID- 23876228
TI  - Initial evidence that OPRM1 genotype moderates ventral and dorsal striatum
      functional connectivity during alcohol cues.
AB  - BACKGROUND: Endogenous opioids and striatal dopamine have been implicated in cue
      induced alcohol craving and have been hypothesized to play a role in goal
      directed, as opposed to habitual, alcohol use. This initial study examines dorsal
      and ventral striatal functional connectivity during alcohol-cue processing as a
      function of the A118G single-nucleotide polymorphism of the mu-opioid receptor
      (OPRM1) gene. METHODS: Seventeen individuals with alcohol dependence (6 females;
      90% Caucasian; mean age = 29.4) underwent blood oxygen level-dependent functional
      magnetic resonance imaging, while performing an alcohol taste-cues task.
      Psychophysiological interaction analyses investigated associations of the OPRM1
      genotype with ventral and dorsal striatum functional connectivity, using the
      ventral striatum and the caudate as the seed region, respectively. RESULTS:
      Compared to A-allele homozygotes, G-allele carriers of the OPRM1 gene showed (i)
      greater activation of the insula and orbitofrontal cortex and (ii) stronger
      negative fronto-striatal functional connectivity for both ventral and dorsal
      striatal seed regions during processing of alcohol versus water cues.
      CONCLUSIONS: These preliminary findings suggest that, relative to A-allele
      homozygotes, G-allele carriers show unstable frontal regulation over reward
      and/or habit-driven inputs from the striatum resulting from greater reward
      sensitivity combined with limited self-control resources.

PMID- 23876230
TI  - Safety and efficacy of noninvasive ventilation in patients with blunt chest
      trauma: a systematic review.
AB  - INTRODUCTION: This systematic review looks at the use of noninvasive ventilation
      (NIV), inclusive of noninvasive positive pressure ventilation (NPPV) and
      continuous positive pressure ventilation (CPAP), in patients with chest trauma to
      determine its safety and clinical efficacy in patients with blunt chest trauma
      who are at high risk of acute lung injury (ALI) and respiratory failure. METHODS:
      We searched the MEDLINE, EMBASE and Cochrane Central Register of Controlled
      Trials (CENTRAL) databases. Pairs of reviewers abstracted relevant clinical data
      and assessed the methodological quality of randomized controlled trials (RCTs)
      using the Cochrane domain and observational studies using the Newcastle-Ottawa
      Scale. RESULTS: Nine studies were included (three RCTs, two retrospective cohort
      studies and four observational studies without a comparison group). There was
      significant heterogeneity among the included studies regarding the severity of
      injuries, degree of hypoxemia and timing of enrollment. One RCT of moderate
      quality assessed the use of NPPV early in the disease process before the
      development of respiratory distress. All others evaluated the use of NPPV and
      CPAP in patients with blunt chest trauma after the development of respiratory
      distress. Overall, up to 18% of patients enrolled in the NIV group needed
      intubation. The duration of NIV use was highly variable, but NIV use itself was
      not associated with significant morbidity or mortality. Four low-quality
      observational studies compared NIV to invasive mechanical ventilation in patients
      with respiratory distress and showed decreased ICU stay (5.3 to 16 days vs 9.5 to
      15 days), complications (0% to 18% vs 38% to 49%) and mortality (0% to 9% vs 6%
      to 50%) in the NIV group. CONCLUSIONS: Early use of NIV in appropriately
      identified patients with chest trauma and without respiratory distress may
      prevent intubation and decrease complications and ICU length of stay. Use of NIV
      to prevent intubation in patients with chest trauma who have ALI associated with
      respiratory distress remains controversial because of the lack of good-quality
      data.

PMID- 23876231
TI  - Synthesis, immunomodulation and cytotoxic effects of vanadium (IV) complexes.
AB  - Vanadium is known to exhibit several bioactivities and shows potential as a
      pharmaceutical drug. The current studies were conducted with the goal of
      synthesizing a new generation of oxovanadium(IV) complexes, investigating their
      effects on cancer cell proliferation and their immunomodulatory properties, and
      predicting possible structure activity relationships. The elucidation of the
      structures of the synthesized complexes was achieved using elemental analysis,
      conductivity measurements, magnetic property measurements, and IR and electronic
      spectroscopies. These studies suggest that the synthesized complexes have a
      binuclear structure. All of the complexes were evaluated on different cancer cell
      lines, including HeLa, PC-3, and C33A, and on the normal 3T3 fibroblast cells.
      Some of the compounds exhibited prominent inhibitory activities on the cervical
      cancer cell lines and the prostate cancer PC-3 cells. The immunomodulatory
      activity of the vanadium compounds was evaluated on human phagocytes for ROS
      (reactive oxygen species) production using luminol- and lucigenin-based
      chemiluminescence assays. No potent effect was exerted by the majority of the
      tested compounds on whole blood oxidative burst activity. A study of human T
      cells proliferation in vitro on vanadium complexes was also conducted. The
      majority of the compounds were observed to exhibit potent inhibitory effects. The
      superoxide, nitric oxide and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical
      scavenging properties were also determined. 

PMID- 23876232
TI  - Diarrhetic shellfish poisoning, Washington, USA, 2011.
AB  - Diarrhetic shellfish poisoning is a gastrointestinal illness caused by
      consumption of bivalves contaminated with dinophysistoxins. We report an illness
      cluster in the United States in which toxins were confirmed in shellfish from a
      commercial harvest area, leading to product recall. Ongoing surveillance is
      needed to prevent similar illness outbreaks. 

PMID- 23876233
TI  - Duck liver-associated outbreak of Campylobacteriosis among humans, United
      Kingdom, 2011.
AB  - Campylobacter- spp.-related gastroenteritis in diners at a catering college
      restaurant was associated with consumption of duck liver pate. Population genetic
      analysis indicated that isolates from duck samples were typical of isolates from
      farmed poultry. Campylobacter spp. contamination of duck liver may present a
      hazard similar to the increasingly recognized contamination of chicken liver. 

PMID- 23876234
TI  - Recurrence of uveitis after discontinuation of infliximab.
AB  - PURPOSE: To evaluate the recurrence of uveitis after discontinuation of
      infliximab once control of inflammation is achieved. METHODS: A retrospective
      cohort study was conducted of patients seen at the Proctor Foundation between
      1998 and 2010 who discontinued infliximab after achieving corticosteroid-sparing
      control by Standardization of Uveitis Nomenclature criteria. The main outcome was
      the proportion of patients who had a relapse of uveitis. RESULTS: Eighteen
      patients attempted to discontinue infliximab after achieving control of
      inflammation, and 11 patients had a relapse. Median time to relapse was 603 days
      (95% CI: 85-1461 days). Patients with juvenile idiopathic arthritis (JIA)
      associated uveitis (n = 4) relapsed faster (median time to relapse: 76 days, p =
      0.002) compared with patients who did not have JIA-associated uveitis (median =
      1169 days). CONCLUSIONS: The majority of patients who achieved control of
      inflammation on infliximab had a recurrence after discontinuing therapy. Patients
      with JIA experienced recurrence faster compared to other patients.

PMID- 23876235
TI  - Global characterization of signalling networks associated with tamoxifen
      resistance in breast cancer.
AB  - Acquired resistance to the anti-estrogen tamoxifen remains a significant
      challenge in breast cancer management. In this study, we used an integrative
      approach to characterize global protein expression and tyrosine phosphorylation
      events in tamoxifen-resistant MCF7 breast cancer cells (TamR) compared with
      parental controls. Quantitative mass spectrometry and computational approaches
      were combined to identify perturbed signalling networks, and candidate regulatory
      proteins were functionally interrogated by siRNA-mediated knockdown. Network
      analysis revealed that cellular metabolism was perturbed in TamR cells, together
      with pathways enriched for proteins associated with growth factor, cell-cell and
      cell matrix-initiated signalling. Consistent with known roles for Ras/MAPK and
      PI3-kinase signalling in tamoxifen resistance, tyrosine-phosphorylated MAPK1,
      SHC1 and PIK3R2 were elevated in TamR cells. Phosphorylation of the tyrosine
      kinase Yes and expression of the actin-binding protein myristoylated alanine-rich
      C-kinase substrate (MARCKS) were increased two- and eightfold in TamR cells
      respectively, and these proteins were selected for further analysis. Knockdown of
      either protein in TamR cells had no effect on anti-estrogen sensitivity, but
      significantly decreased cell motility. MARCKS expression was significantly higher
      in breast cancer cell lines than normal mammary epithelial cells and in ER
      negative versus ER-positive breast cancer cell lines. In primary breast cancers,
      cytoplasmic MARCKS staining was significantly higher in basal-like and HER2
      cancers than in luminal cancers, and was independently predictive of poor
      survival in multivariate analyses of the whole cohort (P < 0.0001) and in ER
      positive patients (P = 0.0005). These findings provide network-level insights
      into the molecular alterations associated with the tamoxifen-resistant phenotype,
      and identify MARCKS as a potential biomarker of therapeutic responsiveness that
      may assist in stratification of patients for optimal therapy.

PMID- 23876237
TI  - Radical formation on a conserved tyrosine residue is crucial for DyP activity.
AB  - Dye-decolorizing peroxidases (DyPs) are able to cleave bulky anthraquinone dyes.
      The recently published crystal structure of AauDyPI reveals that a direct
      oxidation in the distal heme cavity can be excluded for most DyP substrates. It
      is shown that a surface-exposed tyrosine residue acts as a substrate interaction
      site for bulky substrates. This amino acid is conserved in eucaryotic DyPs but is
      missing in the structurally related chlorite dismutases (Clds). Dye-decolorizing
      peroxidases of procaryotic origin equally possess a conserved tyrosine in the
      same region of the polypeptide albeit not at the homologous position. 

PMID- 23876236
TI  - The effects of noncontingent and self-administered cytisine on body weight and
      meal patterns in male Sprague-Dawley rats.
AB  - RATIONALE: Increased appetite and weight gain after cessation are deterrents for
      quitting smoking. Pharmacotherapies that can reduce this weight gain in ex
      smokers would be invaluable, and yet are not well studied in this context.
      OBJECTIVE: To examine the effects of extended daily exposure to intravenous
      cytisine, an alpha4beta2 nAChR partial agonist used for smoking cessation in some
      European countries, on body weight and patterns of food intake in rats. METHODS:
      In the first experiment, programmed infusions of cytisine were administered over
      15 h per day. Food intake, meal patterns, and weight change were examined
      relative to a vehicle-infused group during treatment, and in a post-cytisine
      phase. The second experiment examined the effects of cytisine on food intake,
      meal patterns, and weight change when substituted for nicotine in a self
      administration protocol. Rats self-administered nicotine and cytisine during
      alternating four day periods, and changes in body weight, drug infusions, and
      meal patterns were compared between drugs and during an extinction phase.
      RESULTS: In the first experiment, cytisine-treated rats ate less and gained less
      weight than those that received the vehicle. This occurred primarily by a reduced
      frequency of meals. In the 12 day post-cytisine phase, animals maintained a lower
      body weight relative to controls throughout. In the second experiment, total
      pellet intake increased during cytisine substitution relative to nicotine and
      animals self-administered cytisine significantly less than nicotine. However,
      cytisine substitution maintained decreases in food intake and weight gain
      compared to baseline via decreases in total pellet intake and meal size.
      CONCLUSION: Cytisine administration results in decreased weight gain and changes
      in meal patterns dependent upon mode and pattern of administration and a previous
      history of nicotine administration.

PMID- 23876238
TI  - Biosynthesis of carotenoids in carrot: an underground story comes to light.
AB  - Carrot (Daucus carota) is a biannual plant that accumulates massive amounts of
      carotenoid pigments in the storage root. Although the root of carrot plants was
      white before domestication, intensive breeding generated the currently known
      carotenoid-rich varieties, including the widely popular orange carrots that
      accumulate very high levels of the pro-vitamin A carotenoids beta-carotene and,
      to a lower extent, alpha-carotene. Recent studies have shown that the
      developmental program responsible for the accumulation of these health-promoting
      carotenes in underground roots can be completely altered when roots are exposed
      to light. Illuminated root sections do not enlarge as much as dark-grown roots,
      and they contain chloroplasts with high levels of lutein instead of the beta
      carotene-rich chromoplasts found in underground roots. Analysis of carotenoid
      gene expression in roots either exposed or not to light has contributed to better
      understand the contribution of developmental and environmental cues to the root
      carotenoid profile. In this review, we summarize the main conclusions of this
      work in the context of our current knowledge of how carotenoid biosynthesis and
      accumulation is regulated at transcriptional and post-transcriptional levels in
      carrot roots and other model systems for the study of plant carotenogenesis such
      as Arabidopsis de-etiolation and tomato fruit ripening.

PMID- 23876240
TI  - Effects of the semisynthetic bis-indole derivative KAR-2 on store-operated
      calcium entry in human neutrophils.
AB  - We studied the effect of KAR-2 on cytosolic Ca(2+) level in human neutrophils by
      using a fluorescent dye (Fura-2) trapped in the cells. KAR-2 is a semisynthetic
      bis-indole derivative that shares vinblastine anti-microtubular properties, but
      does not share the vinblastine antagonistic effect on calmodulin. Therefore KAR-2
      offers a convenient mean of studying the effect of microtubule destabilization,
      without concomitant calmodulin alterations. We found that KAR-2 induces Ca(2+)
      release from intracellular stores, whereby the stores are depleted. In addition
      KAR-2 reduces store-operated entry of extracellular Ca(2+) induced by agonists
      such as thapsigargin or ATP. On the other hand, in Ca(2+) refilled cells, KAR-2
      promotes limited entry of extracellular Ca(2+) in the absence of agonist, but
      still interferes prominently with Ca(2+) entry triggered by ATP and with Ca(2+)
      uptake by intracellular stores. We suggest that Ca(2+) traffic through the plasma
      membrane is operated by two diverse pathways: the prominent pathway is interfered
      with by microtubule destabilization, while an alternate and minor pathway is
      actually favored (or uncovered) following microtubule destabilization.

PMID- 23876239
TI  - Carotenoids as possible interphotoreceptor retinoid-binding protein (IRBP)
      ligands: a surface plasmon resonance (SPR) based study.
AB  - Uptake, transport and stabilization of xanthophylls in the human retina are
      important components of a complex multistep process that culminates in a non
      uniform distribution of these important nutrients in the retina. The process is
      far from understood; here, we consider the potential role of interphotoreceptor
      retinoid-binding protein (IRBP) in this process. IRBP is thought to facilitate
      the exchange of 11-cis-retinal, 11-cis-retinol and all-trans-retinol between the
      retinal pigment epithelium (RPE), photoreceptors and Muller cells in the visual
      cycle. Structural and biochemical studies suggest that IRBP has a variety of
      nonequivalent ligand binding sites that function in this process. IRBP is
      multifunctional, being able to bind a variety of physiologically significant
      molecules including fatty acids in the subretinal space. This wide range of
      binding activities is of particular interest because it is unknown whether the
      lutein and zeaxanthin found in the macula originate from the choroidal or retinal
      circulations. If from the choroidal circulation, then IRBP is a likely mediator
      for their transport across the interphotoreceptor matrix. In this report, we
      explore the binding interactions of retinoids, fatty acids, and carotenoids with
      IRBP using surface plasmon resonance (SPR)-based biosensors. IRBP showed similar
      affinity toward retinoids and carotenoids (1-2 MUM), while fatty acids had
      approximately 10 times less affinity. These results suggest that further studies
      should be carried out to evaluate whether IRBP has a physiologically relevant
      role in binding lutein and zeaxanthin in the interphotoreceptor matrix.

PMID- 23876241
TI  - Phage-displayed peptide library screening for preferred human substrate peptide
      sequences for transglutaminase 7.
AB  - Transglutaminases are a family of enzymes that catalyze cross-linking reactions
      between proteins. Among the members, there is currently no information regarding
      the substrate preferences of transglutaminase 7 (TG7), that would clarify its
      physiological significance. We previously obtained several highly reactive
      substrate peptide sequences of transglutaminases from a random peptide library.
      In this study, we screened for preferred substrate sequences for TG7 from a phage
      displayed 12-mer peptide library. The most preferred sequence was selected based
      on reactivity and isozyme specificity. We firstly exhibited the tendency for the
      preference of substrate sequence for TG7. Then, using the most efficient peptide,
      Z3S, we established an in vitro assay system to assess enzymatic activity of TG7.

PMID- 23876242
TI  - Relationship between excitability, plasticity and thickness of the motor cortex
      in older adults.
AB  - The relationship between brain structure, cortical physiology, and learning
      ability in older adults is of particular interest in understanding mechanisms of
      age-related cognitive decline. Only a few studies addressed this issue so far,
      yielding mixed results. Here, we used comprehensive multiple regression analyses
      to investigate associations between brain structure on the one hand, i.e.,
      cortical thickness (CT), fractional anisotropy (FA) of the pyramidal tract and
      individual coil-to-cortex distance, and cortical physiology on the other hand,
      i.e. motor cortex excitability and long-term potentiation (LTP)-like cortical
      plasticity, in healthy older adults (mean age 64 years, 14 women). Additional
      exploratory analyses assessed correlations between cortical physiology and
      learning ability in the verbal domain. In the regression models, we found that
      cortical excitability could be best predicted by CT of the hand knob of the
      primary motor cortex (CT-M1HAND) and individual coil-to-cortex distance, while
      LTP-like cortical plasticity was predicted by CT-M1HAND and FA of the pyramidal
      tract. Exploratory analyses revealed a significant inverse correlation between
      cortical excitability and learning ability. In conclusion, higher cortical
      excitability was associated with lower CT and lower learning ability in a cohort
      of healthy older adults, in line with previous reports of increased cortical
      excitability in patients with cortical atrophy and cognitive deficits due to
      Alzheimer's Disease. Cortical excitability may thus be a parameter to identify
      individuals at risk for cognitive decline and gray matter atrophy, a hypothesis
      to be explored in future longitudinal studies.

PMID- 23876244
TI  - Spontaneous and electrically modulated spatiotemporal dynamics of the neocortical
      slow oscillation and associated local fast activity.
AB  - The neocortical slow oscillation (SO; ~1Hz) of non-REM sleep and anesthesia
      reflects synchronized network activity composed of alternating active and silent
      (ON/OFF) phases at the local network and cellular level. The SO itself shows self
      organized spatiotemporal dynamics as it appears to originate at unique foci on
      each cycle and then propagates across the cortical surface. During sleep, this
      rhythm is relevant for neuroplastic processes mediating memory consolidation
      especially since its enhancement by slow, rhythmic electrical fields improves
      subsequent recall. However, the neurobiological mechanism by which spontaneous or
      enhanced SO activity might operate on memory traces is unknown. Here we show a
      series of original results, using cycle to cycle tracking across multiple
      neocortical sites in urethane anesthetized rats: The spontaneous spatiotemporal
      dynamics of the SO are complex, showing interfering propagation patterns in the
      anterior-to-posterior plane. These patterns compete for expression and tend to
      alternate following phase resets that take place during the silent OFF phase of
      the SO. Applying sinusoidal electrical field stimulation to the anterior pole of
      the cerebral cortex progressively entrained local field, gamma, and multi-unit
      activity at all sites, while disrupting the coordination of endogenous SO
      activity. Field stimulation also biased propagation in the anterior-to-posterior
      direction and more notably, enhanced the long-range gamma synchrony between
      cortical regions. These results are the first to show that changes to slow wave
      dynamics cause enhancements in high frequency cortico-cortical communication and
      provide mechanistic clues into how the SO is relevant for sleep-dependent memory
      consolidation. 

PMID- 23876243
TI  - Sex differences in the development of brain mechanisms for processing biological
      motion.
AB  - Disorders related to social functioning including autism and schizophrenia differ
      drastically in incidence and severity between males and females. Little is known
      about the neural systems underlying these sex-linked differences in risk and
      resiliency. Using functional magnetic resonance imaging and a task involving the
      visual perception of point-light displays of coherent and scrambled biological
      motion, we discovered sex differences in the development of neural systems for
      basic social perception. In adults, we identified enhanced activity during
      coherent biological motion perception in females relative to males in a network
      of brain regions previously implicated in social perception including amygdala,
      medial temporal gyrus, and temporal pole. These sex differences were less
      pronounced in our sample of school-age youth. We hypothesize that the robust
      neural circuitry supporting social perception in females, which diverges from
      males beginning in childhood, may underlie sex differences in disorders related
      to social processing. 

PMID- 23876245
TI  - High-order interactions observed in multi-task intrinsic networks are dominant
      indicators of aberrant brain function in schizophrenia.
AB  - Identifying the complex activity relationships present in rich, modern
      neuroimaging data sets remains a key challenge for neuroscience. The problem is
      hard because (a) the underlying spatial and temporal networks may be nonlinear
      and multivariate and (b) the observed data may be driven by numerous latent
      factors. Further, modern experiments often produce data sets containing multiple
      stimulus contexts or tasks processed by the same subjects. Fusing such multi
      session data sets may reveal additional structure, but raises further statistical
      challenges. We present a novel analysis method for extracting complex activity
      networks from such multifaceted imaging data sets. Compared to previous methods,
      we choose a new point in the trade-off space, sacrificing detailed generative
      probability models and explicit latent variable inference in order to achieve
      robust estimation of multivariate, nonlinear group factors ("network clusters").
      We apply our method to identify relationships of task-specific intrinsic networks
      in schizophrenia patients and control subjects from a large fMRI study. After
      identifying network-clusters characterized by within- and between-task
      interactions, we find significant differences between patient and control groups
      in interaction strength among networks. Our results are consistent with known
      findings of brain regions exhibiting deviations in schizophrenic patients.
      However, we also find high-order, nonlinear interactions that discriminate groups
      but that are not detected by linear, pairwise methods. We additionally identify
      high-order relationships that provide new insights into schizophrenia but that
      have not been found by traditional univariate or second-order methods. Overall,
      our approach can identify key relationships that are missed by existing analysis
      methods, without losing the ability to find relationships that are known to be
      important. 

PMID- 23876246
TI  - Don't stand so close to me: a behavioral and ERP study of preferred interpersonal
      distance.
AB  - The space between people, or interpersonal distance, creates and defines the
      dynamics of social interactions. Given that invasion of one's interpersonal space
      may trigger threat and anxiety, a critical question is if high vulnerability to
      social anxiety (SA) is associated with avoidance and attentional biases when
      anticipating invasion to one's interpersonal space. Therefore, the current study
      sought to examine the behavioral mechanisms, time course and neural correlates
      underlying the threat of interpersonal distance invasion with a focus on
      different SA levels, using both a behavioral and an ERP experiment. Preferred
      interpersonal distance was assessed using a paradigm that involves responding to
      different virtual protagonists (friend or stranger) approaching the participant
      by indicating where one would like the protagonist to stop. In addition,
      participants' level of social anxiety was measured. The behavioral experiment
      indicated that levels of SA predicted one's preferred interpersonal distance such
      that higher SA individuals preferred further distance from a stranger. At the
      neural level, across groups, early (N1) but not late (LPP) differences were found
      between stranger and friend conditions. Importantly, SA individuals were
      characterized by attenuated early ERP responses, suggesting less attentional
      resources allocated to social stimuli. The results suggest that high SA
      individuals feel discomfort earlier than others in social engagement, which may
      lead them to stand further away, thus creating less communicative social
      interactions. 

PMID- 23876247
TI  - An approach for parcellating human cortical areas using resting-state
      correlations.
AB  - Resting State Functional Connectivity (RSFC) reveals properties related to the
      brain's underlying organization and function. Features related to RSFC signals,
      such as the locations where the patterns of RSFC exhibit abrupt transitions, can
      be used to identify putative boundaries between cortical areas (RSFC-Boundary
      Mapping). The locations of RSFC-based area boundaries are consistent across
      independent groups of subjects. RSFC-based parcellation converges with
      parcellation information from other modalities in many locations, including task
      evoked activity and probabilistic estimates of cellular architecture, providing
      evidence for the ability of RSFC to parcellate brain structures into functionally
      meaningful units. We not only highlight a collection of these observations, but
      also point out several limitations and observations that mandate careful
      consideration in using and interpreting RSFC for the purposes of parcellating the
      brain's cortical and subcortical structures.

PMID- 23876249
TI  - Lower theta inter-trial phase coherence during performance monitoring is related
      to higher reaction time variability: a lifespan study.
AB  - Trial-to-trial reaction time (RT) variability is consistently higher in children
      and older adults than in younger adults. Converging evidence also indicates that
      higher RT variability is (a) associated with lower behavioral performance on
      complex cognitive tasks, (b) distinguishes patients with neurological deficits
      from healthy individuals, and also (c) predicts longitudinal cognitive decline in
      older adults. However, so far the processes underlying increased RT variability
      are poorly understood. Previous evidence suggests that control signals in the
      medial frontal cortex (MFC) are reflected in theta band activity and may
      implicate the coordination of distinct brain areas during performance monitoring.
      We hypothesized that greater trial-to-trial variability in theta power during
      performance monitoring may be associated with greater behavioral variability in
      response latencies. We analyzed event-related theta oscillations assessed during
      a cued-Go/NoGo task in a lifespan sample covering the age range from middle
      childhood to old age. Our results show that theta inter-trial coherence during
      NoGo trials increases from childhood to early adulthood, and decreases from early
      adulthood to old age. Moreover, in all age groups, individuals with higher
      variability in medial frontal stimulus-locked theta oscillations showed higher
      trial-to-trial RT variability behaviorally. Importantly, this effect was
      strongest at high performance monitoring demands and independent of motor
      response execution as well as theta power. Taken together, our findings reveal
      that lower theta inter-trial coherence is related to greater behavioral
      variability within and across age groups. These results hint at the possibility
      that more variable MFC control may be associated with greater performance
      fluctuations. 

PMID- 23876248
TI  - Neural correlates of time-varying functional connectivity in the rat.
AB  - Functional connectivity between brain regions, measured with resting state
      functional magnetic resonance imaging, holds great potential for understanding
      the basis of behavior and neuropsychiatric diseases. Recently it has become clear
      that correlations between the blood oxygenation level dependent (BOLD) signals
      from different areas vary over the course of a typical scan (6-10 min in length),
      though the changes are obscured by standard methods of analysis that assume the
      relationships are stationary. Unfortunately, because similar variability is
      observed in signals that share no temporal information, it is unclear which
      dynamic changes are related to underlying neural events. To examine this
      question, BOLD data were recorded simultaneously with local field potentials
      (LFP) from interhemispheric primary somatosensory cortex (SI) in anesthetized
      rats. LFP signals were converted into band-limited power (BLP) signals including
      delta, theta, alpha, beta and gamma. Correlation between signals from
      interhemispheric SI was performed in sliding windows to produce signals of
      correlation over time for BOLD and each BLP band. Both BOLD and BLP signals
      showed large changes in correlation over time and the changes in BOLD were
      significantly correlated to the changes in BLP. The strongest relationship was
      seen when using the theta, beta and gamma bands. Interestingly, while steady
      state BOLD and BLP correlate with the global fMRI signal, dynamic BOLD becomes
      more like dynamic BLP after the global signal is regressed. As BOLD sliding
      window connectivity is partially reflecting underlying LFP changes, the present
      study suggests it may be a valuable method of studying dynamic changes in brain
      states.

PMID- 23876250
TI  - Mechanical and transport properties of layer-by-layer electrospun composite
      proton exchange membranes for fuel cell applications.
AB  - Composite membranes composed of highly conductive and selective layer-by-layer
      (LbL) films and electrospun fiber mats were fabricated and characterized for
      mechanical strength and electrochemical selectivity. The LbL component consists
      of a proton-conducting, methanol-blocking poly(diallyl dimethyl ammonium
      chloride)/sulfonated poly(2,6-dimethyl-1,4-phenylene oxide) (PDAC/sPPO) thin
      film. The electrospun fiber component consists of poly(trimethyl hexamethylene
      terephthalamide) (PA 6(3)T) fibers in a nonwoven mat of 60-90% porosity. The bare
      mats were annealed to improve their mechanical properties, which improvements are
      shown to be retained in the composite membranes. Spray LbL assembly was used as a
      means for the rapid formation of proton-conducting films that fill the void space
      throughout the porous electrospun matrix and create a fuel-blocking layer. Coated
      mats as thin as 15 MUm were fabricated, and viable composite membranes with
      methanol permeabilities 20 times lower than Nafion and through-plane proton
      selectivity five and a half times greater than Nafion are demonstrated. The
      mechanical properties of the spray coated electrospun mats are shown to be
      superior to the LbL-only system and possess intrinsically greater dimensional
      stability and lower mechanical hysteresis than Nafion under hydrated conditions.
      The composite proton exchange membranes fabricated here were tested in an
      operational direct methanol fuel cell. The results show the potential for higher
      open circuit voltages (OCV) and comparable cell resistances when compared to fuel
      cells based on Nafion. 

PMID- 23876251
TI  - The effect of nonprobative photographs on truthiness persists over time.
AB  - When making rapid judgments about the truth of a claim, related nonprobative
      information leads people to believe the claim-an effect called "truthiness"
      (Newman, Garry, Bernstein, Kantner, & Lindsay, 2012). For instance, within a
      matter of seconds, subjects judge the claim "The Mona Lisa has no eyebrows," to
      be true more often when it appears with a photograph of the Mona Lisa viewed at a
      distance by a person. But does truthiness persist longer than a few seconds? To
      determine if truthiness "sticks," we asked people to judge if each trivia claim
      in a series was true. Half of the claims appeared with nonprobative photos; the
      rest appeared alone. In a second session 48h later, people returned and made the
      same judgments about the same statements, but this time, all claims appeared
      without photos. We found that truthiness "stuck." The magnitude of the effect of
      photos on subjective feelings of truth was consistent over time. These results
      fit with those from cognitive and educational psychology, as well as with the
      related idea that photos make relevant information more available and familiar
      and therefore feel more true-even after a delay. 

PMID- 23876252
TI  - Genotype GI.6 norovirus, United States, 2010-2012.
AB  - We report an increase in the proportion of genotype GI.6 norovirus outbreaks in
      the United States from 1.4% in 2010 to 7.7% in 2012 (p<0.001). Compared with non
      GI.6 outbreaks, GI.6 outbreaks were characterized by summer seasonality,
      foodborne transmission, and non-health care settings. 

PMID- 23876253
TI  - Lipopolysaccharide-induced blood brain barrier permeability is enhanced by alpha
      synuclein expression.
AB  - Because alpha-synuclein (Snca) is involved in neuroinflammatory response, we
      determined if its expression altered blood-brain barrier (BBB) permeability. To
      induce increased BBB permeability, Snca gene-ablated (KO) and wild-type (WT) mice
      were injected (i.p.) with lipopolysaccharide (LPS). To assess changes in BBB
      permeability, Evans blue was injected (i.p.) and extravasation into the brain
      assessed using fluorescence spectroscopy. WT mice had a significant increase in
      BBB permeability at 1, 3, and 6h post-injection of LPS relative to untreated
      mice. Contrary to WT mice, LPS did not induce a time-dependent change in BBB
      permeability in KO mice. Although brain edema is associated with increased BBB
      permeability, no significant difference in edema was found between groups. These
      results show that Snca expression is associated with increased reactive opening
      of the BBB in response to LPS.

PMID- 23876254
TI  - Oxidative degradation of azo dyes using tourmaline.
AB  - This study aimed to investigate the catalyzed degradation ability of tourmaline
      on the dyes methylene blue (MB), rhodamine B (RhB), and congo red (CR) at
      different pH values. Interestingly, tourmaline strongly adsorbed anionic dyes,
      but it did not adsorb cationic dyes. When H2O2 was introduced into the tourmaline
      dye systems, the degradation percentage for CR catalysis by tourmaline was lower
      than the percentage of adsorption, whereas the opposite was true for MB and RhB
      systems. Notably, the catalyzed degradation decreased from 100% to 45% for MB,
      100% to 15% for RhB and 100% to 25% for CR as the pH increased from 3.0 to 10.0,
      respectively, which was much greater than the degradation obtained for previously
      reported materials at pH values ranging from 4.0 to 10.0. Tourmaline
      catalytically degraded the dyes over a broad range of pH values, which was
      attributed to tourmaline automatically adjusting the pH of the dye solutions to
      approximately 5.5 from an initial range of 4.2-10.0. An electron paramagnetic
      resonance spin trapping technique observed peroxyl (ROO.) and alkoxy (RO.) or
      alkyl (R.) radicals originated from the attack of .OH radicals and O2(.-)
      radicals, indicating that these radicals were involved in the catalyzed
      degradation of MB. Importantly, four intermediate products of MB at m/z 383, 316,
      203 and 181 were observed by LC/MS.

PMID- 23876255
TI  - Regenerable sorbents for mercury capture in simulated coal combustion flue gas.
AB  - This work demonstrates that regenerable sorbents containing nano-particles of
      gold dispersed on an activated carbon are efficient and long-life materials for
      capturing mercury species from coal combustion flue gases. These sorbents can be
      used in such a way that the high investment entailed in their preparation will be
      compensated for by the recovery of all valuable materials. The characteristics of
      the support and dispersion of gold in the carbon surface influence the efficiency
      and lifetime of the sorbents. The main factor that determines the retention of
      mercury and the regeneration of the sorbent is the presence of reactive gases
      that enhance mercury retention capacity. The capture of mercury is a consequence
      of two mechanisms: (i) the retention of elemental mercury by amalgamation with
      gold and (ii) the retention of oxidized mercury on the activated carbon support.
      These sorbents were specifically designed for retaining the mercury remaining in
      gas phase after the desulfurization units in coal power plants. 

PMID- 23876256
TI  - Remediation of an aquifer polluted with dissolved tetrachloroethylene by an array
      of wells filled with activated carbon.
AB  - In this work, an array of deep passive wells filled with activated carbon, namely
      a Discontinuous Permeable Adsorptive Barrier (PAB-D), has been proposed for the
      remediation of an aquifer contaminated by tetrachloroethylene (PCE). The dynamics
      of the aquifer in the particular PAB-D configuration chosen, including the
      contaminant transport in the aquifer and the adsorption onto the barrier
      material, has been accurately performed by means of a computer code which allows
      describing all the phenomena occurring in the aquifer, simultaneously. A PAB-D
      design procedure is presented and the main dimensions of the barrier (number and
      position of passive wells) have been evaluated. Numerical simulations have been
      carried out over a long time span to follow the contaminant plume and to assess
      the effectiveness of the remediation method proposed. The model results show that
      this PAB-D design allows for a complete remediation of the aquifer under a
      natural hydraulic gradient, the PCE concentrations flowing out of the barrier
      being always lower than the corresponding Italian regulation limit. Finally, the
      results have been compared with those obtained for the design of a more
      traditional continuous barrier (PAB-C) for the same remediation process. 

PMID- 23876257
TI  - The mechanism of hydrogen sulfide adsorption on fine rubber particle media
      (FRPM).
AB  - A commercial rubber waste product, fine rubber particle media (FRPM), was found
      to adsorb hydrogen sulfide (H2S) at 0.12 mg H2S/g FRPM of adsorption capacity.
      Since FRPM seems to be an attractive alternative to treat H2S owing to its
      economic advantages as well as its physicochemical characteristics, several
      analyses were conducted to investigate fundamental information, surface
      properties, and breakthrough characteristics of FRPM as adsorbent. The physical
      properties of FRPM including composition and surface chemistry were investigated
      to compare its performance with commonly available commercial H2S adsorbents such
      as activated carbon and assess the possible adsorption mechanism. The specific
      surface area of FRPM was less than 1% of activated carbon. FRPM does not have
      enough surface area supporting a pure physical adsorption of H2S because it is
      particulate in nature with limited porosity. The adsorption of FRPM to remove H2S
      was complex mechanism and involved a combination of zinc compounds and carbon
      black.

PMID- 23876258
TI  - Stereoselective transformation of triadimefon to metabolite triadimenol in wheat
      and soil under field conditions.
AB  - Racemic triadimefon (TF) was applied to wheat and soil at three sites (Beijing,
      Huaibei, and Zhengzhou in China) under open field conditions. Its
      enantioselective degradation and stereoselective transformation to the major
      metabolite, triadimenol (TN), in wheat straw, grain and soil were investigated.
      At all sites, the degradation of TF enantiomers in straw and soil followed first
      order kinetics. In soil from Beijing and Zhengzhou R-(-)-TF was preferentially
      degraded; however, preferential enantioselective degradations were not recorded
      in soil from Huaibei or in the straw from all sites. There were noticeable
      differences in the stereoselective formation of TN stereoisomers in all straw and
      soil samples. TN diastereomer A with high animal toxicity was preferentially
      produced via a reductive reaction in straw. In contrast, diastereomer B, was
      preferential in soil across the experimental period. Different TN concentrations
      were found in the order of SR-(-)-TN>RR-(+)-TN>RS-(+)-TN>SS-(-)-TN in straw, and
      RR-(+)-TN>SS-(-)-TN>SR-(-)-TN>RS-(+)-TN in soil. Neither TF nor TN was found in
      wheat grain at harvest. Because of differences in degradation, formation, and
      toxicity, the characterization of enantiomers and stereoisomers in this study
      contributes toward comprehensively assessing the fate and risk of chiral
      agrochemicals in the environment and food. 

PMID- 23876259
TI  - Nursing's contribution to the changing face of children's health care.

PMID- 23876260
TI  - Voices not heard: a systematic review of adolescents' and emerging adults'
      perspectives of health care transition.
AB  - BACKGROUND: A better understanding of the needs of adolescents and emerging
      adults with special health care needs (AEA-SHCNs) is essential to provide health
      care transition services that represent best practices. The purpose of this
      systematic review was to evaluate the research on health care transition for AEA
      SHCNs from their perspectives. METHODS: A comprehensive literature review of
      research publications since 2005 was performed using the PubMed, Cumulative Index
      to Nursing and Allied Health Literature, and EBSCO databases. Thirty-five studies
      met the final review criteria. RESULTS: The process of transition from child to
      adult for AEA-SHCNs is complex. Individuals experiencing the transition desire to
      be a part of the process and want providers who will listen and be sensitive to
      their needs, which are often different from others receiving health care at the
      same facility. CONCLUSIONS: More research that considers the voice of the AEA
      SHCNs related to transition from pediatric to adult care is needed.

PMID- 23876261
TI  - Comparison of PD BLADE with fat saturation (FS), PD FS and T2 3D DESS with water
      excitation (WE) in detecting articular knee cartilage defects.
AB  - The purpose of this study, is to compare the sequences: 1) proton density (PD)
      BLADE (BLADE is a PROPELLER-equivalent implementation of the Siemens Medical
      System) with fat saturation (FS) coronal (COR), 2) PD FS COR, 3) multi-planar
      reconstruction (MPR) with 3mm slice thickness and 4) multi-planar reconstruction
      (MPR) with 1.5mm slice thickness, both from the T2 3D-double-echo steady state
      (DESS) with water excitation (WE) sagittal (SAG), regarding their abilities to
      identify changes in the femorotibial condyle cartilage in knee MRI examinations.
      Thirty three consecutive patients with osteoarthritis (18 females, 15 males; mean
      age 56years, range 37-71years), who had been routinely scanned for knee
      examination using the previously mentioned image acquisition techniques,
      participated in the study. A quantitative analysis was performed based on the
      relative contrast (ReCON) measurements, which were taken both on normal tissues
      as well as on pathologies. Additionally, a qualitative analysis was performed by
      two radiologists. Motion and pulsatile flow artifacts were evaluated. The PD
      BLADE FS COR sequence produced images of higher contrast between Menisci and
      Cartilage, Fluid and Cartilage, Pathologies and Cartilage as well as of the
      Conspicuousness Superficial Cartilage and it was found to be superior to the
      other sequences (p<0.001). The sequences T2 3D DESS 1.5mm and T2 3D DESS 3mm were
      significantly superior to the PD BLADE FS COR and the PD FS COR sequences in the
      visualization of Bone and Cartilage and the Conspicuousness Deep Surface
      Cartilage. This pattern of results is also confirmed by the quantitative
      analysis. PD FS BLADE sequences are ideal for the depiction of the cartilage
      pathologies compared to the conventional PD FS and T2 3D DESS sequences. 

PMID- 23876262
TI  - Breath-held MR cholangiopancreatography (MRCP) using a 3D Dixon fat-water
      separated balanced steady state free precession sequence.
AB  - A novel 3D breath-held Dixon fat-water separated balanced steady state free
      precession (b-SSFP) sequence for MR cholangiopancreatography (MRCP) is described
      and its potential clinical utility assessed in a series of patients. The main
      motivation is to develop a robust breath-held alternative to the respiratory
      gated 3D Fast Spin Echo (FSE) sequence, the current clinical sequence of choice
      for MRCP. Respiratory gated acquisitions are susceptible to motion artifacts and
      blurring in patients with significant diaphragmatic drift, erratic respiratory
      rhythms or sleep apnea. A two point Dixon fat-water separation scheme was
      developed which eliminates signal loss arising from B0 inhomogeneity effects and
      minimizes artifacts from perturbation of the b-SSFP steady state. Preliminary
      results from qualitative analysis of 49 patients demonstrate robust performance
      of the 3D Dixon b-SSFP sequence with diagnostic image quality acquired in a 20
      24s breath-hold. 

PMID- 23876264
TI  - Family-wise automatic classification in schizophrenia.
AB  - Automatic classification of individuals at increased risk for schizophrenia can
      become an important screening method that allows for early intervention based on
      disease markers, if proven to be sufficiently accurate. Conventional
      classification methods typically consider information from single subjects,
      thereby ignoring (heritable) features of the person's relatives. In this paper we
      show that the inclusion of these features can lead to an increase in
      classification accuracy from 0.54 to 0.72 using a support vector machine model.
      This inclusion of contextual information is especially useful in diseases where
      the classification features carry a heritable component. 

PMID- 23876263
TI  - Prospective observational evaluation of the particle immunofiltration anti
      platelet factor 4 rapid assay in MICU patients with thrombocytopenia.
AB  - INTRODUCTION: Heparin-induced thrombocytopenia (HIT) results from antibodies to
      PF4/heparin complexes and clinical diagnosis is difficult. We evaluated the
      particle immunofiltration anti-platelet factor 4 (PIFA) rapid assay, in
      conjunction with a clinical risk score, in the diagnosis of HIT. METHODS: We
      performed a prospective observational study in all patients admitted to the
      medical intensive care unit (MICU) in a large academic medical center. Patients
      were screened daily for thrombocytopenia defined as either a platelet count that
      decreased by at least 33% or an absolute platelet count less than 150,000/MUL.
      Patients with suspected HIT underwent PIFA and ELISA testing for anti-PF4/heparin
      antibodies. Available residual frozen sera were sent to a reference laboratory
      for serotonin release assay (SRA) testing. RESULTS: During the study period, 340
      patients were admitted to the MICU, of which 143 patients met criteria for
      thrombocytopenia. Forty-three patients had no evidence of recent heparin
      exposure. PIFA and ELISA testing were performed on 100 patients, of which 92 had
      samples available for SRA analysis. PIFA results were negative in 62, positive in
      28 and inconclusive in 2 patients. The 4Ts score showed low to intermediate risk
      in 57 of the PIFA negative patients. The ELISA results were negative in 86 and
      positive in 6 patients. SRA testing identified 3 patients with a positive SRA
      test and 89 patients with a negative result. All patients with a negative PIFA
      result also had a negative SRA result. In the one patient deemed to have clinical
      HIT, the pretest probability was high (4Ts score of 6) and the anti-PF4/heparin
      antibody testing revealed a positive SRA, inconclusive PIFA and a negative ELISA
      result. CONCLUSIONS: While thrombocytopenia in our population is common, the
      prevalence of HIT is low. The combination of a low to intermediate pretest
      probability with a negative PIFA test can rapidly exclude the presence of
      platelet activating anti-PF4/heparin antibodies and, therefore, HIT as the cause
      of the thrombocytopenia. Since a positive PIFA result has a low positive
      predictive value, a positive PIFA is not diagnostic of HIT and additional
      evaluation is warranted.

PMID- 23876266
TI  - [RAM now in Elsevier].

PMID- 23876265
TI  - [Isolation of Aspergillus section Nigri strains in yerba mate in Posadas
      (Misiones, Argentina) and evaluation of their ochratoxigenic potential].
AB  - The objectives of the present work were to investigate the isolation frequency of
      genus Aspergillus in canchada yerba mate (YMCH) and elaborated yerba mate (YME)
      (Ilex paraguariensis) and the proportion of section Nigri isolates, as well as to
      determine ochratoxin A production by Aspergillus species section Nigri. Three
      hundred twenty eight Aspergillus strains from 20 samples of YMCH and 1306
      Aspergillus strains from 36 samples of YME were isolated; of the total, 279 from
      the first group of strains and 1215 from the latter group, belonged to section
      Nigri. For the detection of ochratoxin A production, the strains were cultivated
      on Czapeck yeast extract agar and the toxin was detected by thin layer
      chromatography under UV light. Uniserate species predominance was observed in the
      1494 strains of Aspergillus section Nigri obtained (Aspergillus japonicus var.
      japonicus and Aspergillus japonicus var. aculeatus), whereas none of the strains
      analysed showed ochratoxin A production in vitro at the detection level of the
      methodology employed. 

PMID- 23876267
TI  - Enhancing adherence of Arcobacter butzleri after serial intraperitoneal passages
      in mice.
AB  - We investigated the possibility of enhancing the adherence capacity of four low
      adherent Arcobacter butzleri strains after serial intraperitoneal passage (i.p.)
      in mice. All the strains enhanced their adherence capacity after the first
      passage, increasing their adhesion rates after each passage. These results
      suggest that i.p. passage enhances the expression of adherence in A. butzleri
      strains. 

PMID- 23876268
TI  - [Evaluation of a purified antigen for the diagnosis of toxocariosis].
AB  - Toxocarosis is a zoonotic disease caused by the ingestion of infective eggs of
      Toxocara spp. The diagnosis is based on the detection of antibodies in serum or
      other biological fluids. One of the current serological techniques for the
      diagnosis of toxocariasis is ELISA using excretory - secretory antigens of third
      stage larvae (ES/L3). These antigens are glycoproteins, which originate in the
      secretory organs of the parasite and are non species-specific. Sera from patients
      with other helminthiases and non- parasitic diseases were used to evaluate the
      specificity of ELISA using the excretory - secretory antigen (ES/L3). The
      reactivity of these sera was between 11 and 70%. Western blot using patients'
      sera revealed that the glycoprotein triplet having a molecular weight of 120 kDa
      was responsible for cross-reactivity. With these results, and for the purpose of
      purifying the antigen, ion exchange chromatography was performed. When the sera
      from patients with various parasitic and non-parasitic diseases were analyzed
      with the purified antigen ES/ L3, they were only reactive between 10 to 20%. The
      sensitivity of the ELISA test determined by program Epidat 3.0 for the two
      antigens was 100%, but the following differences in specificity were observed:
      84% for the total antigen ES/L3 and 99% for purified ES/L3. Using the ES/L3
      purified antigen, it can be considered that the reactive sera, with compatible
      symptoms correspond to patients who are or were parasitized with Toxocara canis. 

PMID- 23876269
TI  - [Bordetella holmesii endocarditis in an asplenic patient].
AB  - The case of a 52-year-old female patient with a history of critical aortic
      stenosis, hypothyroidism and splenectomy as treatment for her Hodgkin's lymphoma
      is herein presented. In April 2011, the patient was admitted to the cardiology
      service due to global heart failure, fever and poor response to diuretic and
      vasodilator therapy. A transesophageal echocardiogram showed images compatible
      with vegetations in the aortic, pulmonary, and mitral valves. A diagnosis of
      infective endocarditis was made. Growth of gram-negative coccobacilli was
      observed in two blood culture sets. The microorganism was finally identified as
      Bordetella holmesii. The patient was treated with ceftriaxone 1 g every 12 hours
      for 28 days with favorable outcome. 

PMID- 23876270
TI  - [Genotyping of Cryptococcus neoformans/Cryptococcus gattii complex clinical
      isolates from Hospital "Dr. Julio C. Perrando", Resistencia city (Chaco,
      Argentina)].
AB  - Cryptococcosis is a fungal infection caused by yeast species of Cryptococcus
      genus, particularly Cryptococcus neoformans/Cryptococcus gattii species complex.
      The knowledge of the cryptococcosis casuistic in northeastern Argentina is scarce
      and there is no information about the molecular types circulating in this area.
      The aim of this study was to genotyping C. neoformans/C. gattii complex clinical
      isolates obtained at Hospital "Dr. Julio C. Perrando", Resistencia city (Chaco,
      Argentina), in order to determine species, variety and molecular type. During two
      years and one month 26 clinical isolates were studied. Using conventional and
      molecular methods one isolate was identified as C. gattii VGI type, and 25
      isolates as C. neoformans var. grubii; 23 of these belonged to VNI type and two
      belonged to VNII type. This data is a contribution to the knowledge of
      cryptococcosis epidemiology in Argentina and the first report about C.
      neoformans/ C. gattii complex molecular types from clinical isolates in
      northeastern Argentina. 

PMID- 23876271
TI  - Antimicrobial activity of yerba mate (Ilex paraguariensis St. Hil.) against food
      pathogens.
AB  - Yerba mate (Ilex paraguariensis St. Hil.) has been studied for its important
      biological activities mainly attributed to phenolic compounds. This study
      evaluated the antimicrobial activity of methanolic and ethanolic extracts of
      yerba mate against food pathogens, such as Staphylococcus aureus, Listeria
      monocytogenes, Salmonella Enteritidis and Escherichia coli through minimum
      inhibitory (MIC) and bactericidal (MBC) concentrations, in addition to the
      determination of chemical composition by gas chromatography with mass
      spectrometry (GC-MS) and phenolic content. The most effective extract had its
      activity evaluated under different pH conditions by growth curve analysis. All
      microorganisms except E. coli were inhibited. The ethanolic extract showed the
      lowest MIC/MBC (0.78/0.78 mg/ml), the highest phenolic content (193.9 g.GAE/kg)
      and the presence of chlorogenic acid derivatives, especially 3-O-caffeoylquinic
      and caffeic acid. This extract was able to inhibit microbial growth at pH 7 and
      8. 

PMID- 23876272
TI  - [First isolation in Argentina of community-acquired methicillin-resistant
      Staphylococcus aureus with intermediate susceptibility to vancomycin and
      nonsusceptibility to daptomycin].
AB  - We report the first case in Argentina of community-acquired methicillin-resistant
      Staphylococcus aureus with intermediate susceptibility to vancomycin and
      nonsusceptibility to daptomycin. CASE REPORT: A male patient with a history of
      chronic renal failure on hemodialysis and hip fracture osteosynthesis was
      admitted to hospital for persistent febrile syndrome following the displacement
      of the prosthesis by trauma. Blood cultures grew community-acquired methicillin
      resistant Staphylococcus aureus. During treatment with vancomycin and daptomycin,
      a gradual increase in vancomycin MIC of 1 MUg/ml (VSSA) to 2 MUg/ml (h-VISA) and
      4 MUg/ml (VISA) was observed, as well as the emergence of non-susceptibility to
      daptomycin (MIC = 4 MUg/ml). By suspending vancomycin and daptomycin, the strain
      reversed to the susceptible phenotype to both drugs. It is mandatory to evaluate
      by MIC the susceptibility to vancomycin and daptomycin during treatment when
      these drugs are used as therapy.

PMID- 23876273
TI  - [Dissemination of blaIMP-8 among Enterobacteriaceae isolates from a Buenos Aires
      Hospital].
AB  - From August 2008 to December 2011, six metallo-beta-lactamase-producing isolates,
      four Enterobacter cloacae, one Klebsiella oxytoca and one Citrobacter freundii,
      were detected at Hospital Interzonal General de Agudos "Evita" in Lanus. All six
      isolates showed multiresistant profiles and the presence of the blaIMP-8 gene.
      Five isolates also expressed PER-2 extended spectrum beta-lactamase. The blaIMP-8
      gene was found as the first cassette in a class 1 integron. However, the 3'
      conserved sequence could not be detected in three isolates. In all cases, blaIMP
      8 was transferred by conjugation to azide-resistant Escherichia coli J53. PFGE
      analysis revealed that the four E. cloacae isolates were not genetically related.
      These are the first metallo-beta-lactamases detected in this institution and our
      results suggest a possible intra- and inter-species horizontal dissemination of
      blaIMP-8. 

PMID- 23876274
TI  - Differential effects of two strains of Rhizophagus intraradices on dry biomass
      and essential oil yield and composition in Calamintha nepeta.
AB  - The aim of this work was to determine the effects of two geographically different
      strains of Rhizophagus intraradices (M3 and GA5) on the total biomass and
      essential oil (EO) yield and composition of Calamintha nepeta, with or without
      phosphorus (P) fertilization, under greenhouse conditions. The plant biomass was
      not significantly affected by any of the treatments, showing higher values in
      control plants. Strains had a differential response in their root colonization
      rates: M3 reduced these parameters while GA5 did not modify them. Both strains
      affected EO yield in absence of P fertilization: M3 promoted EO yield in C.
      nepeta plants and GA5 resulted in negative effects. The percentage composition of
      EO was not significantly modified by either strain or P fertilization. M3 strain
      could be a potential fungal bioinoculant for production and commercialization of
      C. nepeta in the aromatic plant market. 

PMID- 23876275
TI  - [Virulence factors of Staphylococcus aureus associated with intramammary
      infections in cows: relevance and role as immunogens].
AB  - Staphylococcus aureus is the most prevalent mastitis pathogen in Argentina and
      worldwide. Lack of effectiveness of traditional control measures based on milking
      hygiene and antibiotic therapy against this organism has led to the development
      of alternatives directed to prevent the disease. Among them, the manipulation of
      host immune mechanisms through vaccination has been explored. The identification
      of virulence factors able to stimulate host immune defenses is key to developing
      a rational vaccine. S. aureus has multiple virulence factors that interact with
      the host at different stages of an intramammary infection. The use of some of
      these factors as immunogens has been shown to elicit protective responses in the
      host. The structure, function, and use as immunogens of S. aureus virulence
      factors considered to be relevant at different stages of intrammamary infections
      caused by this organism are reviewed in this article. 

PMID- 23876276
TI  - [Arbuscular mycorrhizae and Rhizobium: a dual symbiosis of interest].

PMID- 23876277
TI  - [Imported malaria in Buenos Aires City: diagnosis of 2 cases].

PMID- 23876279
TI  - [Occult primary MALT lymphoma of the breast diagnosed and treated by reduction
      mammaplasty. An exceptional case report and review of the literature].
AB  - Primary Mucosa-associated Lymphoid Tissue (MALT) lymphoma of the breast is a very
      rare disease. We report here a case of occult primary MALT lymphoma of the breast
      diagnosed from a mammaplasty specimen. Primary tumor resection during the
      mammaplasty surgery was the only treatment of this lymphoma, and there was no
      recurrence at five years. The clinical and radiologic presentation of primary
      MALT lymphoma of the breast is similar to epithelial breast carcinoma, and the
      main diagnostic criteria are microscopic examination and immunohistochemistry.
      The prognosis of breast primary MALT lymphomas is good after local treatment by
      surgery and/or radiotherapy, and surgery shouldn't be too aggressive. In this
      case, no other treatment was indicated after the first surgical procedure. To our
      knowledge, this is the first case report in the literature of occult primary MALT
      lymphoma of the breast diagnosed from a mammaplasty specimen. This allows us to
      highlight the need for systematic microscopic examination of mammaplasty
      specimens conducted by an experienced pathologist, especially as preoperative
      examinations are not able to detect all occult breast carcinomas. 

PMID- 23876280
TI  - Precursors of cognitive impairments in psychotic disorders: a population-based
      study.
AB  - Cognitive deficits have been found to be more prevalent in psychotic than in
      other disorders. Longitudinal research has shown that these deficits were
      generally already existent before onset of illness and are therefore not
      necessarily attributable to neurodegenerative processes. This study investigated
      whether both low IQ and markers of premorbid cognitive dysfunction independently
      contribute to an increased risk for psychoses. In a cross-sectional study about
      50,000 young Swiss males completed a survey of intellectual problems in
      childhood/adolescence and other vulnerability factors during military call-up in
      2005/2006. Subsequently, military IQ assessments were carried out on the entire
      sample. Diagnostic assessments were conducted according to International
      Classification of Diseases-10th edition (ICD-10). Low, especially performance, IQ
      was highly associated with an increased risk for psychotic disorders after
      adjusting for preexisting cognitive deficits and covariates, while in other
      disorders this association was less marked. Furthermore, preexisting intellectual
      problems emerged as important risk factors for psychoses. Our results confirm the
      importance of low IQ as characteristic of psychoses. Although premorbid
      intellectual deficits are common in people who go on to develop psychosis,
      neurodegenerative disease processes may also precipitate further declines in
      fluid cognitive functions. Assessment of cognitive functioning should be taken
      into account in early detection of psychoses. 

PMID- 23876278
TI  - Host blood meal-dependent growth ensures transovarial transmission and
      transstadial passage of Rickettsia sp. phylotype G021 in the western black-legged
      tick (Ixodes pacificus).
AB  - In this study, we explored the growth dynamics of Rickettsia sp. phylotype G021
      during transovarial transmission and transstadial passage by Ixodes pacificus
      using real-time quantitative PCR. Four parental engorged I. pacificus females
      were allowed to complete their developmental stages until the F2-generation eggs
      yielded unfed larvae. All eggs, larvae, nymphs, and adults tested through 2
      generations were found to be infected with phylotype G021. Hence, we conclude
      that the efficiency of transovarial transmission and transstadial passage of this
      phylotype in I. pacificus was 100%. Acquisition of a blood meal by all 3
      parasitic stages (larva, nymph, adult) significantly increased the rickettsial
      burden as fed larvae, nymphs, and adults had respective 19-, 12-, and 313-fold
      increases of rickettsiae compared with unfed ticks representing each
      developmental stage. I. pacificus eggs contained high rickettsial burdens at the
      time of oviposition. While I. pacificus egg cells underwent rapid proliferation
      during early embryonic development, the rickettsiae remained relatively
      quiescent, which resulted in depressed numbers of phylotype G021 per tick cell.
      However, the rickettsial burden remained constant over a period of 56 days, as
      the rate of I. pacificus cell division slowed during later embryonic development.

PMID- 23876281
TI  - Blunted stress cortisol reactivity and failure to acclimate to familiar stress in
      depressed and sub-syndromal children.
AB  - Depressed adults have shown blunted or elevated cortisol reactivity in response
      to various forms of psychosocial stress. However, there have been few studies of
      cortisol reactivity in children who had early onset depression or a history of
      depression during the preschool-school period. The present study utilized a
      laboratory stress paradigm and collected salivary cortisol from preschoolers at
      baseline (ages 3-5 years) and 24-month follow-up (ages 5-7 years). Repeated
      measures multivariate analyses of variance (MANOVAs) were used to compare
      cortisol reactivity to mild stress between children with Major Depressive
      Disorder (MDD), elevated symptoms of depression (sub-syndromal MDD), and healthy
      controls. For healthy children, a quadratic cortisol reactivity curve was found
      at baseline (n=73), which appeared flatter under similar stressful situations at
      follow-up (n=14), which may reflect acclimation to the paradigm. In contrast,
      children with MDD (n=46) and sub-syndromal MDD (n=76) showed a peak cortisol
      response to the novelty of lab arrival and then reduced and blunted responses to
      stressors at baseline. These cortisol responses persisted at follow-up in
      children with a history of MDD (n=41) or sub-syndromal MDD (n=73). These results
      suggest that the hypothalamic-pituitary-adrenal (HPA) axis shows a blunted
      response to stress and failed to acclimate to familiar stressful situations in
      depressed and sub-syndromal depressed children. 

PMID- 23876282
TI  - Specific music therapy techniques in the treatment of primary headache disorders
      in adolescents: a randomized attention-placebo-controlled trial.
AB  - Migraine and tension-type headache have a high prevalence in children and
      adolescents. In addition to common pharmacologic and nonpharmacologic
      interventions, music therapy has been shown to be efficient in the prophylaxis of
      pediatric migraine. This study aimed to assess the efficacy of specific music
      therapy techniques in the treatment of adolescents with primary headache (tension
      type headache and migraine). A prospective, randomized, attention-placebo
      controlled parallel group trial was conducted. Following an 8-week baseline,
      patients were randomized to either music therapy (n = 40) or a rhythm pedagogic
      program (n = 38) designed as an "attention placebo" over 6 sessions within 8
      weeks. Reduction of both headache frequency and intensity after treatment (8-week
      postline) as well as 6 months after treatment were taken as the efficacy
      variables. Treatments were delivered in equal dose and frequency by the same
      group of therapists. Data analysis of subjects completing the protocol showed
      that neither treatment was superior to the other at any point of measurement
      (posttreatment and follow-up). Intention-to-treat analysis revealed no impact of
      drop-out on these results. Both groups showed a moderate mean reduction of
      headache frequency posttreatment of about 20%, but only small numbers of
      responders (50% frequency reduction). Follow-up data showed no significant
      deteriorations or improvements. PERSPECTIVE: This article presents a randomized
      placebo-controlled trial on music therapy in the treatment of adolescents with
      frequent primary headache. Music therapy is not superior to an attention placebo
      within this study. These results draw attention to the need of providing adequate
      controls within therapeutic trials in the treatment of pain.

PMID- 23876283
TI  - Impaired recognition of social emotion in patients with complex regional pain
      syndrome.
AB  - Multiple brain areas involved in nociceptive, autonomic, and social-emotional
      processing are disproportionally changed in patients with complex regional pain
      syndrome (CRPS). Little empirical evidence is available involving social
      cognitive functioning in patients with chronic pain conditions. We investigated
      the ability of patients with CRPS to recognize the mental/emotional states of
      other people. Forty-three patients with CRPS and 30 healthy controls performed
      the Reading Mind in the Eyes Test, which consists of photos in which human eyes
      express various emotional and mental states. Neuropsychological tests, including
      the Wisconsin Card Sorting Test, the stop-signal test, and the reaction time
      test, were administered to evaluate other cognitive functions. Patients with CRPS
      were significantly less accurate at recognizing emotional states in other
      persons, but not on other cognitive tests, compared with control subjects. We
      found a significant association between the deficit in social-emotion recognition
      and the affective dimension of pain, whereas this deficit was not related to the
      sensory dimension of pain. Our findings suggest a disrupted ability to recognize
      others' mental/emotional states in patients with CRPS. PERSPECTIVE: This article
      demonstrated a deficit in inferring mental/emotional states of others in patients
      with CRPS that was related to pain affect. Our study suggests that additional
      interventions directed toward reducing distressful affective pain may be helpful
      to restore social cognitive processing in patients with CRPS.

PMID- 23876284
TI  - Rapid advances in understanding viral gastroenteritis from domestic surveillance.

PMID- 23876285
TI  - Suprasellar and sellar paraganglioma presenting as a nonfunctioning pituitary
      macroadenoma.
AB  - It is extremely rare for paragangliomas to be present in the brain. We present a
      44-year-old man with a suprasellar-sellar paraganglioma encasing the internal
      carotid arteries. We review all such tumors reported in the literature and
      conclude that paraganglioma should be kept in the differential diagnosis of
      unusual suprasellar-sellar lesions. 

PMID- 23876286
TI  - Role of attention in the generation and modulation of tinnitus.
AB  - Neural mechanisms that detect changes in the auditory environment appear to rely
      on processes that predict sensory state. Here we propose that in tinnitus there
      is a disparity between what the brain predicts it should be hearing (this
      prediction based on aberrant neural activity occurring in cortical frequency
      regions affected by hearing loss and underlying the tinnitus percept) and the
      acoustic information that is delivered to the brain by the damaged cochlea. The
      disparity between the predicted and delivered inputs activates a system for
      auditory attention that facilitates through subcortical neuromodulatory systems
      neuroplastic changes that contribute to the generation of tinnitus. We review
      behavioral and functional brain imaging evidence for persisting auditory
      attention in tinnitus and present a qualitative model for how attention operates
      in normal hearing and may be triggered in tinnitus accompanied by hearing loss.
      The viewpoint has implications for the role of cochlear pathology in tinnitus,
      for neural plasticity and the contribution of forebrain neuromodulatory systems
      in tinnitus, and for tinnitus management and treatment. 

PMID- 23876287
TI  - Habenula and ADHD: convergence on time.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a childhood-onset psychiatric
      condition characterized by hyperactivity, impulsivity, and attention deficit. In
      addition to these core symptoms, accumulating evidence suggests that ADHD may
      also involve alterations in circadian rhythms, sleep disturbance, and time
      perception. The habenula is a brain region transmitting limbic information to the
      midbrain monoamine systems and is thereby involved in the regulation of monoamine
      release in such target brain areas as the striatum, where it is part of the
      biological substrates that process time perception. The habenula is additionally
      a part of the circadian rhythm network and is involved in sleep regulation. Our
      recent study provides a new insight that a habenula lesion created early in
      development produces behavioral and brain alterations resembling those observed
      in ADHD. We propose that the habenula may be a promising target for understanding
      the pathogenesis of ADHD. 

PMID- 23876288
TI  - Characterizing the cognitive effects of cocaine: a comprehensive review.
AB  - Understanding the cognitive sequela of repeated cocaine use is a growing area of
      research and is crucial to the development of cognitive models of addiction. We
      systematically reviewed all available placebo-controlled and case-controlled
      studies on the acute and long-term effects of cocaine on cognitive functioning.
      In order to compare the magnitude of cognitive effects across cognitive domains
      we conducted several meta-analyses on a subset of data from long-term effect
      studies. Studies on acute cocaine administration suggest enhancement of response
      inhibition and psychomotor speed, while all other domains appear to be unaffected
      or not investigated adequately. Long-term effects of cocaine show a wide array of
      deteriorated cognitive functions, indicating that long term cocaine use is
      characterized by a general cognitive impairment across functions, rather than by
      specific cognitive deficits. Literature on long-term cocaine effects is more
      substantial than literature on acute effects. This comprehensive review outlines
      possible dissociations and similarities of acute vs. long-term cocaine effects in
      the human brain. Atherosclerosis after cocaine exposure may underlie cognitive
      dysfunction, suggesting involvement of multiple brain areas. Acute drug studies
      are important to the future development of addiction models. 

PMID- 23876289
TI  - Protein conformational changes involved in the cytochrome bc1 complex catalytic
      cycle.
AB  - Early structures of the cytochrome bc1 complex revealed heterogeneity in the
      position of the soluble portion of the Rieske iron sulfur protein subunit,
      implicating a movement of this domain during function. Subsequent biochemical and
      biophysical works have firmly established that the motion of this subunit acts in
      the capacity of a conformationally assisted electron transfer step during the
      already complicated catalytic mechanism described within the modified version of
      Peter Mitchells Q cycle. How the movement of this subunit is initiated or how the
      frequency of its motion is controlled as a function of other steps during the
      catalysis remain topics of debate within the active research communities. This
      review addresses the historical aspects of the discovery and description of this
      movement, while attempting to provide a context for the involvement of
      conformational motion in the catalysis and efficiency of the enzyme. This article
      is part of a Special Issue entitled: Respiratory complex III and related bc
      complexes. 

PMID- 23876290
TI  - Chloroplast genome analysis of Australian eucalypts--Eucalyptus, Corymbia,
      Angophora, Allosyncarpia and Stockwellia (Myrtaceae).
AB  - We present a phylogenetic analysis and comparison of structural features of
      chloroplast genomes for 39 species of the eucalypt group (genera Eucalyptus,
      Corymbia, Angophora, and outgroups Allosyncarpia and Stockwellia). We use 41
      complete chloroplast genome sequences, adding 39 finished-quality chloroplast
      genomes to two previously published genomes. Maximum parsimony and Bayesian
      analyses, based on >7000 variable nucleotide positions, produced one fully
      resolved phylogenetic tree (35 supported nodes, 27 with 100% bootstrap support).
      Eucalyptus and its sister lineage Angophora+Corymbia show a deep divergence.
      Within Eucalyptus, three lineages are resolved: the 'eudesmid', 'symphyomyrt' and
      'monocalypt' groups. Corymbia is paraphyletic with respect to Angophora. Gene
      content and order do not vary among eucalypt chloroplasts; length mutations,
      especially frame shifts, are uncommon in protein-coding genes. Some non
      synonymous mutations are highly incongruent with the overall phylogenetic signal,
      notably in rbcL, and may be adaptive. Application of custom informatics pipelines
      (GYDLE Inc.) enabled direct chloroplast genome assembly, resolving each genome to
      finished-quality with no need for PCR gap-filling or contig order resolution.
      Analysis of whole chloroplast genomes resolved major eucalypt clades and revealed
      variable regions of the genome that will be useful in lower-level genetic studies
      (including phylogeography and geneflow). 

PMID- 23876291
TI  - Are flatfishes (Pleuronectiformes) monophyletic?
AB  - All extant species of flatfish (order Pleuronectiformes) are thought to descend
      from a common ancestor, and therefore to represent a monophyletic group. This
      hypothesis is based largely on the dramatic bilateral asymmetry and associated
      ocular migration characteristics of all flatfish. Yet, molecular-based
      phylogenetic studies have been inconclusive on this premise. Support for flatfish
      monophyly has varied with differences in taxonomic and gene region sampling
      schemes. Notably, the genus Psettodes has been found to be more related to non
      flatfishes than to other flatfishes in many recent studies. The polyphyletic
      nature of the Pleuronectiformes is often inferred to be the result of weak
      historical signal and/or artifact of phylogenetic inference due to a bias in the
      data. In this study, we address the question of pleuronectiform monophyly with a
      broad set of markers (from six phylogenetically informative nuclear loci) and
      inference methods designed to limit the influence of phylogenetic artifacts.
      Concomitant with a character-rich analytical strategy, an extensive taxonomic
      sampling of flatfish and potential close relatives is used to increase power and
      resolution. Results of our analyses are most consistent with a non-monophyletic
      Pleuronectiformes with Psettodes always being excluded. A fossil-calibrated
      Bayesian relaxed clock analysis estimates the age of Pleuronectoidei to be 73 Ma,
      and the time to most recent common ancestor of Pleuronectoidei, Psettodes, and
      other relative taxa to be 77 Ma. The ages are much older than the records of any
      fossil pleuronectiform currently recognized. We discuss our findings in the
      context of the available morphological evidence and discuss the compatibility of
      our molecular hypothesis with morphological data regarding extinct and extant
      flatfish forms.

PMID- 23876292
TI  - Integrative species delimitation in photosynthetic sea slugs reveals twenty
      candidate species in three nominal taxa studied for drug discovery, plastid
      symbiosis or biological control.
AB  - DNA barcoding can highlight taxa in which conventional taxonomy underestimates
      species richness, identifying mitochondrial lineages that may correspond to
      unrecognized species. However, key assumptions of barcoding remain untested for
      many groups of soft-bodied marine invertebrates with poorly resolved taxonomy.
      Here, we applied an integrative approach for species delimitation to herbivorous
      sea slugs in clade Sacoglossa, in which unrecognized diversity may complicate
      studies of drug discovery, plastid endosymbiosis, and biological control. Using
      the mitochondrial barcoding COI gene and the nuclear histone 3 gene, we tested
      the hypothesis that three widely distributed "species" each comprised a complex
      of independently evolving lineages. Morphological and reproductive characters
      were then used to evaluate whether each lineage was distinguishable as a
      candidate species. The "circumtropical" Elysia ornata comprised a Caribbean
      species and four Indo-Pacific candidate species that are potential sources of
      kahalalides, anti-cancer compounds. The "monotypic" and highly photosynthetic
      Plakobranchus ocellatus, used for over 60 years to study chloroplast symbiosis,
      comprised 10 candidate species. Finally, six candidate species were distinguished
      in the Elysia tomentosa complex, including potential biological control agents
      for invasive green algae (Caulerpa spp.). We show that a candidate species
      approach developed for vertebrates effectively categorizes cryptic diversity in
      marine invertebrates, and that integrating threshold COI distances with non
      molecular character data can delimit species even when common assumptions of DNA
      barcoding are violated.

PMID- 23876293
TI  - Knockdown of both mitochondrial isocitrate dehydrogenase enzymes in pancreatic
      beta cells inhibits insulin secretion.
AB  - BACKGROUND: There are three isocitrate dehydrogenases (IDHs) in the pancreatic
      insulin cell; IDH1 (cytosolic) and IDH2 (mitochondrial) use NADP(H). IDH3 is
      mitochondrial, uses NAD(H) and was believed to be the IDH that supports the
      citric acid cycle. METHODS: With shRNAs targeting mRNAs for these enzymes we
      generated cell lines from INS-1 832/13 cells with severe (80%-90%) knockdown of
      the mitochondrial IDHs separately and together in the same cell line. RESULTS:
      With knockdown of both mitochondrial IDH's mRNA, enzyme activity and protein
      level, (but not with knockdown of only one mitochondrial IDH) glucose- and BCH
      (an allosteric activator of glutamate dehydrogenase)-plus-glutamine-stimulated
      insulin release were inhibited. Cellular levels of citrate, alpha-ketoglutarate,
      malate and ATP were altered in patterns consistent with blockage at the
      mitochondrial IDH reactions. We were able to generate only 50% knockdown of Idh1
      mRNA in multiple cell lines (without inhibition of insulin release) possibly
      because greater knockdown of IDH1 was not compatible with cell line survival.
      CONCLUSIONS: The mitochondrial IDHs are redundant for insulin secretion. When
      both enzymes are severely knocked down, their low activities (possibly assisted
      by transport of IDH products and other metabolic intermediates from the cytosol
      into mitochondria) are sufficient for cell growth, but inadequate for insulin
      secretion when the requirement for intermediates is certainly more rapid. The
      results also indicate that IDH2 can support the citric acid cycle. GENERAL
      SIGNIFICANCE: As almost all mammalian cells possess substantial amounts of all
      three IDH enzymes, the biological principles suggested by these results are
      probably extrapolatable to many tissues.

PMID- 23876294
TI  - Mechanism of action of novel synthetic dodecapeptides against Candida albicans.
AB  - BACKGROUND: Three de novo designed low molecular weight cationic peptides (IJ2,
      IJ3 and IJ4) containing an unnatural amino acid alpha,beta-didehydrophenylalanine
      (?Phe) exhibited potent antifungal activity against fluconazole (FLC) sensitive
      and resistant clinical isolates of Candida albicans as well as non-albicans and
      other yeast and filamentous pathogenic fungi. In the present study, their
      synthesis, susceptibility of different fungi and the mechanism of anti-candidal
      action have been elucidated. METHODS: The antimicrobial peptides (AMPs) were
      synthesized by solid-phase method and checked for antifungal activity against
      different yeasts and fungi by broth microdilution method. Anti-candidal mode of
      action of the peptides was investigated through detecting membrane
      permeabilization by confocal microscopy, Reactive Oxygen Species (ROS) generation
      by fluorometry, apoptosis and necrosis by flow cytometry and cell wall damage
      using Scanning and Transmission Electron Microscopy. RESULTS AND CONCLUSIONS: The
      MIC of the peptides against C. albicans and other yeast and filamentous fungal
      pathogens ranged between 3.91 and 250MUM. All three peptides exhibited effect on
      multiple targets in C. albicans including disruption of cell wall structures,
      compromised cell membrane permeability leading to their enhanced entry into the
      cells, accumulation of ROS and induction of apoptosis. The peptides also showed
      synergistic effect when used in combination with fluconazole (FLC) and
      caspofungin (CAS) against C. albicans. GENERAL SIGNIFICANCE: The study suggests
      that the AMPs alone or in combination with conventional antifungals hold promise
      for the control of fungal pathogens, and need to be further explored for
      treatment of fungal infections.

PMID- 23876295
TI  - Flavoprotein miniSOG as a genetically encoded photosensitizer for cancer cells.
AB  - BACKGROUND: Genetically encoded photosensitizers are a promising optogenetic
      instrument for light-induced production of reactive oxygen species in desired
      locations within cells in vitro or whole body in vivo. Only two such
      photosensitizers are currently known, GFP-like protein KillerRed and FMN-binding
      protein miniSOG. In this work we studied phototoxic effects of miniSOG in cancer
      cells. METHODS: HeLa Kyoto cell lines stably expressing miniSOG in different
      localizations, namely, plasma membrane, mitochondria or chromatin (fused with
      histone H2B) were created. Phototoxicity of miniSOG was tested on the cells in
      vitro and tumor xenografts in vivo. RESULTS: Blue light induced pronounced cell
      death in all three cell lines in a dose-dependent manner. Caspase 3 activation
      was characteristic of illuminated cells with mitochondria- and chromatin
      localized miniSOG, but not with miniSOG in the plasma membrane. In addition, H2B
      miniSOG-expressing cells demonstrated light-induced activation of DNA repair
      machinery, which indicates massive damage of genomic DNA. In contrast to these in
      vitro data, no detectable phototoxicity was observed on tumor xenografts with
      HeLa Kyoto cell lines expressing mitochondria- or chromatin-localized miniSOG.
      CONCLUSIONS: miniSOG is an excellent genetically encoded photosensitizer for
      mammalian cells in vitro, but it is inferior to KillerRed in the HeLa tumor.
      GENERAL SIGNIFICANCE: This is the first study to assess phototoxicity of miniSOG
      in cancer cells. The results suggest an effective ontogenetic tool and may be of
      interest for molecular and cell biology and biomedical applications.

PMID- 23876296
TI  - Minimum detection limit and spatial resolution of thin-sample field-emission
      electron probe microanalysis.
AB  - The minimum detection limit and spatial resolution for a thinned semiconductor
      sample were determined by electron probe microanalysis (EPMA) using a Schottky
      field emission (FE) electron gun and wavelength dispersive X-ray spectrometry.
      Comparison of the FE-EPMA results with those obtained using energy dispersive X
      ray spectrometry in conjunction with scanning transmission electron microscopy,
      confirmed that FE-EPMA is largely superior in terms of detection sensitivity.
      Thin-sample FE-EPMA is demonstrated as a very effective method for high
      resolution, high sensitivity analysis in a laboratory environment because a high
      probe current and high signal-to-noise ratio can be achieved. 

PMID- 23876297
TI  - Detection of novel rotavirus strain by vaccine postlicensure surveillance.
AB  - Surveillance for rotavirus-associated diarrhea after implementation of rotavirus
      vaccination can assess vaccine effectiveness and identify disease-associated
      genotypes. During active vaccine postlicensure surveillance in the United States,
      we found a novel rotavirus genotype, G14P[24], in a stool sample from a child who
      had diarrhea. Unusual rotavirus strains may become more prevalent after vaccine
      implementation. 

PMID- 23876298
TI  - Impact of interpersonal adversity in childhood on adult mental health: how much
      is mediated by social support and socio-economic status in Japan?
AB  - OBJECTIVES: To examine the extent to which social support and socio-economic
      status (SES) in adulthood mediate the impact of interpersonal adversity in
      childhood on adult mental health using large-scale population data in Japan.
      STUDY DESIGN: Cross-sectional survey. METHODS: Data were derived from the
      Japanese Study of Stratification, Health, Income and Neighbourhood, which was
      conducted from October 2010 to February 2011 in four municipalities in and around
      the Tokyo metropolitan area. Survey participants were community residents aged 25
      50 years who were selected at random from voter registration lists. The total
      sample size was 3292. The self-reported experience of parental maltreatment
      (physical abuse and/or neglect) and bullying in school and their impacts on adult
      mental health (in terms of K6 = 5+, K6 = 13+ and suicide ideation) were examined
      using multivariate logistic models. RESULTS: Interpersonal adversity in childhood
      has a negative impact on adult mental health even after controlling for childhood
      SES. For example, the odds ratio for K6 = 5+, responding to parental
      maltreatment, was 2.64 (95% confidence interval 2.04-3.41). Perceived social
      support and adult SES mediated the impact of interpersonal adversity in
      childhood, but a substantial proportion of the impact was unexplained by their
      mediating effects; social support and adult SES only mediated 11-24% and 6-12%,
      respectively. It was also found that social support and adult SES (except
      educational attainment) did not moderate the negative impact of interpersonal
      adversity in childhood. CONCLUSIONS: This analysis highlighted that the impact of
      interpersonal adversity in childhood is relatively independent of social support
      and SES in adulthood. This result has clear policy implications; more focus
      should be placed on policies that aim to reduce incidents of childhood
      maltreatment and bullying per se, both of which have a long-lasting direct impact
      on mental health.

PMID- 23876299
TI  - Identifying the health service needs of homeless adults with physical
      disabilities.

PMID- 23876300
TI  - Physical activity, adiposity and urbanization level in children: results for the
      Italian cohort of the IDEFICS study.
AB  - OBJECTIVES: While there is extensive evidence about the influence of
      environmental factors on adult obesity, fewer studies have assessed how the
      environment influences body fat in children. This cross-sectional study
      investigated the distribution of adiposity indices according to urbanization
      level and patterns of physical activity among children in the Italian cohort of
      the IDEFICS study. METHODS: The sample included 1673 preschool and school-aged
      children (mean age 6.1 years, standard deviation 1.7) living in rural (n = 579),
      suburban (n = 442) and urban (n = 652) areas. Anthropometric measures were taken
      and questionnaires were used to assess children's lifestyles, including patterns
      of physical activity. RESULTS: Children who lived in rural areas spent
      significantly more time in outdoor activities but participated in less structured
      physical activity compared with children living in suburban and urban areas.
      Adiposity estimated by the sum of skinfold thickness increased linearly from
      rural to urban areas, with results for suburban areas showing intermediate
      values. CONCLUSIONS: The data show that geographical environmental factors
      influence patterns of physical activity and body fat in children. In particular,
      the results suggest an association between the time spent in unstructured outdoor
      activities and the degree of adiposity in schoolchildren. These results may have
      implications for public health, including efforts to increase freely available
      playgrounds as an effective measure to counteract the obesity epidemic in
      children.

PMID- 23876301
TI  - Incidence, life expectancy and prognostic factors in cancer patients under
      prolonged mechanical ventilation: a nationwide analysis of 5,138 cases during
      1998-2007.
AB  - INTRODUCTION: This study is aimed at determining the incidence, survival rate,
      life expectancy, quality-adjusted life expectancy (QALE) and prognostic factors
      in patients with cancer in different organ systems undergoing prolonged
      mechanical ventilation (PMV). METHODS: We used data from the National Health
      Insurance Research Database of Taiwan from 1998 to 2007 and linked it with the
      National Mortality Registry to ascertain mortality. Subjects who received PMV,
      defined as having undergone mechanical ventilation continuously for longer than
      21 days, were enrolled. The incidence of cancer patients requiring PMV was
      calculated, with the exception of patients with multiple cancers. The life
      expectancies and QALE of patients with different types of cancer were estimated.
      Quality-of-life data were taken from a sample of 142 patients who received PMV. A
      multivariable proportional hazards model was constructed to assess the effect of
      different prognostic factors, including age, gender, type of cancer, metastasis,
      comorbidities and hospital levels. RESULTS: Among 9,011 cancer patients receiving
      mechanical ventilation for more than 7 days, 5,138 undergoing PMV had a median
      survival of 1.37 months (interquartile range [IQR], 0.50 to 4.57) and a 1-yr
      survival rate of 14.3% (95% confidence interval [CI], 13.3% to 15.3%). The
      incidence of PMV was 10.4 per 100 ICU admissions. Head and neck cancer patients
      seemed to survive the longest. The overall life expectancy was 1.21 years, with
      estimated QALE ranging from 0.17 to 0.37 quality-adjusted life years for patients
      with poor and partial cognition, respectively. Cancer of liver (hazard ratio
      [HR], 1.55; 95% CI, 1.34 to 1.78), lung (HR, 1.45; 95% CI, 1.30 to 1.41) and
      metastasis (HR, 1.53; 95% CI, 1.42 to 1.65) were found to predict shorter
      survival independently. CONCLUSIONS: Cancer patients requiring PMV had poor long
      term outcomes. Palliative care should be considered early in these patients,
      especially when metastasis has occurred.

PMID- 23876302
TI  - Assay validation and technology transfer: problems and solutions.
AB  - In the industry of fine chemicals, including pharmaceutical and agricultural
      chemicals, analytical tests are performed by production departments or contract
      research organizations at some stage in the research and development of products.
      These external organizations are required to maintain the capabilities to perform
      analytical tests using methods that are equivalent to or better than those
      specified by analytical method validation. For this reason, transfer of
      analytical procedures to an alternative site becomes necessary. In this review,
      the relationship between transfer of analytical procedures and assay validation
      is introduced, focusing on analytical procedures that include HPLC. 

PMID- 23876303
TI  - The stimulatory effect of TLRs ligands on maturation of chicken bone marrow
      derived dendritic cells.
AB  - Dendritic cells (DCs) are crucial for initiation of both innate and adaptive
      immune responses. TLR ligands combine with Toll-like receptors (TLRs) expressed
      on the DC surface and induce DC maturation. The potential effect of three types
      of TLR ligands (Bacillus subtilis (B. subtilis) spores, polyinosinic
      polycytidylic acid and CpG oligodeoxynucleotides) on chicken bone marrow-derived
      DCs (chBM-DCs) maturation was studied. The chBM-DCs cultured in presence of
      recombinant chicken granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      interleukin (IL)-4 displayed the typical morphology of DCs after 7 days of
      culture. These immature chBM-DCs up-regulated the expression of MHC-II and of the
      putative CD11c, but had yet low to moderate levels of the CD40 and CD86 co
      stimulatory molecules. After stimulation by the TLR ligands, the chBM-DCs
      displayed a more mature morphologic phenotype, significantly increased the CD40
      and CD86 cell surface expression levels and gained the ability to stimulate
      proliferation of naive T cells in the allogeneic mixed lymphocyte reaction,
      compared to the immature chBM-DCs. In conclusion, our data demonstrated that all
      three TLR ligands were strong stimuli for driving chBM-DCs maturation in vitro,
      with B. subtilis spores being the most efficient. 

PMID- 23876305
TI  - Reagents inducing epidermal proliferation also induce pigmentation: induction of
      keratinocyte proliferation as a novel strategy for the treatment of vitiligo.

PMID- 23876304
TI  - Isolation and characterization of canine natural killer cells.
AB  - NK cells are non-T, non-B lymphocytes that kill target cells without previous
      activation. The immunophenotype and function of these cells in humans and mice
      are well defined, but canine NK cells remain incompletely characterized. Our
      objectives were to isolate and culture canine peripheral blood NK cells, and to
      define their immunophenotype and killing capability. PBMC were obtained from
      healthy dogs and T cells were depleted by immunomagnetic separation. The residual
      cells were cultured in media supplemented with IL-2, IL-15 or both, or with mouse
      embryonic liver (EL) feeder cells. Non-T, non-B lymphocytes survived and expanded
      in these cultures. IL-2 was necessary and sufficient for survival; the addition
      of IL-15 was necessary for expansion, but IL-15 alone did not support survival.
      Culture with EL cells and IL-2 also fostered survival and expansion. The non-T,
      non-B lymphocytes uniformly expressed CD45, MHC I, and showed significant
      cytotoxic activity against CTAC targets. Expression of MHC II, CD11/18 was
      restricted to subsets of these cells. The data show that cells meeting the
      criteria for NK cells in other species, i.e., non-T, non-B lymphocytes with
      cytotoxic activity, can be expanded from canine PBMC by T-cell depletion and
      culture with cytokines or feeder cells. 

PMID- 23876306
TI  - Impact of disease severity on sleep quality in Japanese patients with atopic
      dermatitis.

PMID- 23876307
TI  - Revision surgery for lumbar pseudarthrosis.
AB  - BACKGROUND CONTEXT: Revision surgery for pseudarthrosis after a lumbar spinal
      fusion has unpredictable functional results. PURPOSE: The aim of this study was
      to determine the clinical outcomes of revision surgery to fuse the pseudarthrosis
      site based on the two most common diagnoses (degenerative disc disease [DDD] vs.
      spondylolisthesis). STUDY DESIGN: Patients who had a revision surgery between
      1995 and 2004 for lumbar pseudarthrosis after short segment lumbar spinal fusion
      were identified through the institution's Spine Center surgery database. A
      retrospective chart review of clinical, hospital, and anesthesia records was then
      performed. PATIENT SAMPLE: Sixty-six patients were included in the study (28
      patients with DDD and 38 patients with spondylolisthesis). Inclusion criteria
      were a surgical diagnosis of pseudarthrosis with a prior fusion of one or two
      motion segments, minimum 24 months of follow-up, and a diagnosis of either
      symptomatic DDD or spondylolisthesis as the primary indication for the index
      fusion surgery. OUTCOME MEASURES: The Oswestry disability index (ODI) and a self
      assessment questionnaire were used to evaluate clinical outcomes. METHODS: A
      retrospective chart and radiographic review was performed. Statistical analysis
      was done using Student t test for ODI scores and chi-square test for discrete
      variables from the outcome questionnaires. RESULTS: Follow-up radiographs were
      available for 64 patients (97%), and a fusion rate of 100% was found in both
      groups for the radiographs examined. The mean postoperative ODI score was 53.3
      (30-84.4) for DDD patients and 37.2 (2.5-76) for the spondylolisthesis group
      (p<.01). Only 50% of the patients in the DDD group felt that their overall well
      being had improved since the surgery. In the spondylolisthesis group, 64% of
      patients stated that their overall well-being had improved since their revision
      surgery. CONCLUSIONS: The clinical outcomes after revision surgery for
      pseudarthrosis are worse in patients with DDD compared with spondylolisthesis
      despite successful repair of nonunion. Risks and benefits should be well
      discussed with the patients before deciding on surgical treatment for the
      management of pseudarthrosis, especially in patients with previous short-segment
      fusions done for DDD.

PMID- 23876308
TI  - Pharmacokinetics of dexamethasone after intravenous and intramuscular
      administration in pigs.
AB  - The pharmacokinetics of dexamethasone (DEX) were investigated after an
      intravenous (IV) or intramuscular (IM) bolus injection of 0.3mg/kg bodyweight DEX
      sodium phosphate in pigs. The plasma concentrations of DEX were determined using
      a validated high-performance liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method and the pharmacokinetics were determined by one-compartmental
      analysis. The mean area under the plasma concentration-time curve and the mean
      elimination half-life were 133.07 +/- 39.59 ng.h/mL and 0.77 h, and 173.24 +/-
      53.59 ngh/mL and 1.06 h following IV and IM administration, respectively. The
      volume of distribution and clearance recorded after IV administration were 2.78
      +/- 0.88 L/kg and 2.39 +/- 0.57 L/hkg, respectively. An IM bolus injection of DEX
      sodium phosphate in pigs resulted in a fast and complete absorption, with a mean
      maximal plasma concentration of 80.94 +/- 21.29 ng/mL at 0.35 +/- 0.21 h and a
      high absolute bioavailability of 131.06 +/- 26.05%.

PMID- 23876309
TI  - MDCT of abdominopelvic oncologic emergencies.
AB  - Acute complications arising in abdominopelvic malignancies represent a unique
      subset of patients presenting to the emergency room. The acute presentation can
      be due to complications occurring in the tumor itself or visceral or vascular
      structures harboring the tumor. Multidetector computed tomography (MDCT) is the
      investigation of choice in the workup of these patients and enables appropriate
      and timely management. Management of the complication depends primarily on the
      extent of the underlying malignancy and the involvement of other viscera. The
      purpose of this article is to depict the imaging features of these complications
      on MDCT. 

PMID- 23876310
TI  - Vesicular nucleotide transporter is involved in ATP storage of secretory
      lysosomes in astrocytes.
AB  - Recent studies have suggested that astrocytes release gliotransmitters (i.e.,
      ATP, L-glutamate, D-serine, and peptide hormones) and participate actively in
      synaptic functioning. Although ATP release from astrocytes modulates the activity
      of neurons, the mechanisms regulating the ATP release from astrocytes and the
      source of ATP in astrocytes are not well understood. Recently a vesicular
      nucleotide transporter (VNUT)/solute carrier family 17, member 9 (SLC17A9) has
      been identified as a mediator of the active accumulation of ATP into vesicles.
      Here we show by immunocytochemical analysis under confocal microscope and live
      cell imaging under total internal reflection fluorescence microscope that
      lysosome-associated VNUT is responsible for ATP release in astrocytes. VNUT was
      expressed in both primary cultured cortical astrocytes and glioma cell line C6
      cells, and mainly localized on lysosome in the cells. We found that VNUT
      associated secretory lysosomes do not fully collapse into the plasma membrane
      after lysosomal exocytosis. We also found that inhibition of VNUT function by
      Evans Blue decreased ATP uptake into secretory lysosomes. Depletion and
      inhibition of endogenous VNUT by small interference RNA and Evans Blue,
      respectively decreased the amount of ATP release from the cells, whereas
      overexpression of VNUT increased it. Taken together, these findings indicate that
      the participation of VNUT in ATP storage in secretory lysosomes during lysosomal
      exocytosis of ATP from astrocytes. 

PMID- 23876311
TI  - Biophysical cues enhance myogenesis of human adipose derived stem/stromal cells.
AB  - Adipose-derived stem/stromal cell (ASC)-based tissue engineered muscle grafts
      could provide an effective alternative therapy to autografts - which are limited
      by their availability - for the regeneration of damaged muscle. However, the
      current myogenic potential of ASCs is limited by their low differentiation
      efficiency into myoblasts. The aim of this study was to enhance the myogenic
      response of human ASCs to biochemical cues by providing biophysical stimuli (11%
      cyclic uniaxial strain, 0.5 Hz, 1h/day) to mimic the cues present in the native
      muscle microenvironment. ASCs elongated and fused upon induction with myogenic
      induction medium alone. Yet, their myogenic characteristics were significantly
      enhanced with the addition of biophysical stimulation; the nuclei per cell
      increased approximately 4.5-fold by day 21 in dynamic compared to static
      conditions (23.3 +/- 7.3 vs. 5.2 +/- 1.6, respectively), they aligned at almost
      45 degrees  to the direction of strain, and exhibited significantly higher
      expression of myogenic proteins (desmin, myoD and myosin heavy chain). These
      results demonstrate that mimicking the biophysical cues inherent to the native
      muscle microenvironment in monolayer ASC cultures significantly improves their
      differentiation along the myogenic lineage.

PMID- 23876313
TI  - Binding of Drosophila maternal Mamo protein to chromatin and specific DNA
      sequences.
AB  - Alterations in chromatin structure dynamically occur during germline development
      in Drosophila and are essential for the production of functional gametes. We had
      previously reported that the maternal factor Mamo, which contains both a BTB/POZ
      domain and C2H2 zinc-finger domains and is enriched in primordial germ cells
      (PGCs), is required for the regulation of meiotic chromatin structure and the
      production of functional gametes. However, the molecular mechanisms by which Mamo
      regulates germline development remained unclear. To evaluate the molecular
      function of Mamo protein, we have investigated the binding of Mamo to chromatin
      and DNA sequences. Our data show that Mamo binds to chromatin and specific DNA
      sequences, particularly the polytene chromosomes of salivary gland cells.
      Overexpression of Mamo affected the organization of polytene chromosomes.
      Reduction in maternal Mamo levels impaired the formation of germline-specific
      chromatin structures in PGCs. Furthermore, we found that the zinc-finger domains
      of Mamo directly bind to specific DNA sequences. Our results suggest that Mamo
      plays a role in regulating chromatin structure in PGCs.

PMID- 23876312
TI  - Oxysterols induce transition of monocytic cells to phenotypically mature
      dendritic cell-like cells.
AB  - Dendritic cells (DCs) activate adaptive immune responses in atherosclerotic
      plaques; however, the origin of DCs is in question. We attempted to determine
      whether cholesterol or its oxide forms, which are detected in abundance in
      atheromatous lesions, could induce differentiation or transition of monocytic
      cells to DCs. Treatment of THP-1 cells with 27-hydroxycholesterol (27OH-Chol) and
      7alpha-hydroxycholesterol (7alphaOH-Chol) resulted in an increase in the numbers
      of adherent cells, and, in contrast to PMA, decreased uptake of FITC-conjugated
      dextran. In addition, treatment with 27OH-Chol and 7alphaOH-Chol induced
      expression of mDC-specific molecules, including CD40, CD80, CD83, and CD88. Of
      the two oxysterols, 27OH-Chol enhanced expression of MHC class I and II molecules
      as well as CCR7. However, treatment with an identical concentration of
      cholesterol and 7-ketocholesterol did not influence adherence, uptake of FITC
      conjugated dextran, and expression of the aforementioned molecules. This is the
      first study to report on change of monocytic cells by oxysterols to
      phenotypically atypical cells with some characteristics of mDCs detected in
      atherosclerotic lesions. We propose that a certain type of oxysterol would
      contribute to immune responses in atherosclerotic lesions by enhancing expression
      of multiple CD molecules as well as MHC molecules by monocytic cells. 

PMID- 23876314
TI  - Natural CD8+25+ regulatory T cell-secreted exosomes capable of suppressing
      cytotoxic T lymphocyte-mediated immunity against B16 melanoma.
AB  - Natural CD4(+)25(+) and CD8(+)25(+) regulatory T (Tr) cells have been shown to
      inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are
      crucial for immune regulation. However, immunomodulatory effect of natural Tr
      cell-secreted EXOs is unknown. In this study, we purified natural CD8(+)25(+) Tr
      cells from C57BL/6 mouse naive CD8(+) T cells, and in vitro amplified them with
      CD3/CD28 beads. EXOs (EXO(Tr)) were purified from Tr cell's culture supernatants
      by differential ultracentrifugation and analyzed by electron microscopy, Western
      blot and flow cytometry. Our data showed that EXO(Tr) had a "saucer" or round
      shape with 50-100 nm in diameter, contained EXO-associated markers LAMP-1 and
      CD9, and expressed natural Tr cell markers CD25 and GITR. To assess
      immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)
      pulsed DCs (DC(OVA)) plus Tr cells or EXO(Tr), and then assessed OVA-specific
      CD8(+) T cell responses using PE-H-2K(b)/OVA tetramer and FITC-anti-CD8 antibody
      staining by flow cytometry and antitumor immunity in immunized mice with
      challenge of OVA-expressing BL6-10OVA melanoma cells. We demonstrated that
      DC(OVA)-stimulated CD8(+) T cell responses and protective antitumor immunity
      significantly dropped from 2.52% to 1.08% and 1.81% (p<0.05), and from 8/8 to 2/8
      and 5/8 mice DC(OVA) (p<0.05) in immunized mice with co-injection of Tr cells and
      EXO(Tr), respectively. Our results indicate that natural CD8(+)25(+) Tr cell
      released EXOs, alike CD8(+)25(+) Tr cells, can inhibit CD8(+) T cell responses
      and antitumor immunity. Therefore, EXOs derived from natural CD4(+)25(+) and
      CD8(+)25(+) Tr cells may become an alternative for immunotherapy of autoimmune
      diseases.

PMID- 23876315
TI  - NMR binding and crystal structure reveal that intrinsically-unstructured
      regulatory domain auto-inhibits PAK4 by a mechanism different from that of PAK1.
AB  - Six human PAK members are classified into groups I (PAKs 1-3) and II (PAK4-6).
      Previously, only group I PAKs were thought to be auto-inhibited but very recently
      PAK4, the prototype of group II PAKs, has also been shown to be auto-inhibited by
      its N-terminal regulatory domain. However, the complete auto-inhibitory domain
      (AID) sequence remains undefined and the mechanism underlying its auto-inhibition
      is largely elusive. Here, the N-terminal regulatory domain of PAK4 sufficient for
      auto-inhibiting and binding Cdc42/Rac was characterized to be intrinsically
      unstructured, but nevertheless we identified the entire AID sequence by NMR.
      Strikingly, an AID peptide was derived by deleting the binding-unnecessary
      residues, which has a Kd of 320 nM to the PAK4 catalytic domain. Consequently,
      the PAK4 crystal structure complexed with the entire AID has been determined,
      which reveals that the complete kinase cleft is occupied by 20 AID
      residuescomposed of an N-terminal alpha-helix and a previously-identified
      pseudosubstrate motif, thus achieving auto-inhibition. Our study reveals that
      PAK4 is auto-inhibited by a novel mechanism which is completely different from
      that for PAK1, thus bearing critical implications for design of inhibitors
      specific for group II PAKs.

PMID- 23876316
TI  - The sixth HAMP domain negatively regulates the activity of the group III HHK
      containing seven HAMP domains.
AB  - In fungi, the group III hybrid histidine kinases (HHK) act as important sensors
      to regulate osmoadaptation, hyphal growth, morphogenesis, conidia formation and
      virulence. They are molecular targets for antifungal agent fludioxonil. They
      typically have HAMP domain repeats at the NH2-terminus that are important for
      their activity. Interestingly, the numbers of HAMP domain vary among the
      orthologs from different genera. The orthologs from basidiomycetes harbor seven
      HAMP domains whereas those from yeast contain five HAMP domains. In order to
      understand the functioning of a seven-HAMP module, we have constructed a yeast
      like chimera DhNik1-Tco1 containing seven HAMP domains. The functional
      characterization of this chimera in yeast Saccharomyces cerevisiae showed that
      the sixth HAMP domain played important regulatory role. Our results indicated
      that the negative regulation of histidine kinase activity by the penultimate HAMP
      domain could possibly be an evolutionarily conserved theme in the group III HHK
      containing different lengths of poly HAMP module. 

PMID- 23876317
TI  - Effect of secreted lymphocyte antigen-6/urokinase-type plasminogen activator
      receptor-related peptide-1 (SLURP-1) on airway epithelial cells.
AB  - Acetylcholine (ACh) exerts various anti-inflammatory effects through alpha7
      nicotinic ACh receptors (nAChRs). We have previously shown that secreted
      lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related
      peptide-1 (SLURP-1), a positive allosteric modulator of alpha7 nAChR signaling,
      is down-regulated both in an animal model of asthma and in human epithelial cells
      treated with an inflammatory cytokine related to asthma. Our aim of this study
      was to explore the effect of SLURP-1, signal through alpha7 nAChR, in the
      pathophysiology of airway inflammation. Cytokine production was examined using
      human epithelial cells. Ciliary beat frequency of murine trachea was measured
      using a high speed camera. The IL-6 and TNF-alpha production by human epithelial
      cells was augmented by siRNA of SLURP-1 and alpha7 nicotinic ACh receptor. The
      cytokine production was also dose-dependently suppressed by human recombinant
      SLURP-1 (rSLURP-1). The ciliary beat frequency and amplitude of murine epithelial
      cells were augmented by PNU282987, a selective alpha7 nAChR agonist. Those
      findings suggested that SLURP-1 and stimulus through alpha7 nicotinic ACh
      receptors actively controlled asthmatic condition by stimulating ciliary beating
      and also by suppressing airway inflammation. 

PMID- 23876318
TI  - Beyond discovering the viral agents of acute gastroenteritis.

PMID- 23876319
TI  - Activity and metabolism-related Ca2+ and mitochondrial dynamics in co-cultured
      human fetal cortical neurons and astrocytes.
AB  - Neurons and neighboring astrocytic glia are mostly studied in nervous tissues
      from rodents whereas less is known on their properties and interactions in the
      human brain. Here, confocal/multiphoton fluorescence imaging for several hours
      revealed that co-cultured fetal human cortical neurons and astrocytes show
      pronounced spontaneous rises of cytosolic Ca(2+) which last for up to several
      minutes without concomitant changes in either movements or membrane potential of
      mitochondria. Similar Ca(2+) rises were evoked mainly in neurons by bath-applied
      glutamate or gamma-aminobutyric acid (GABA) acting via N-methyl-d-aspartate
      (NMDA)+AMPA/Kainate and GABAA receptors, respectively. Predominantly in
      astrocytes, Ca(2+) baseline was elevated by adenosine diphosphate (ADP) and
      adenosine triphosphate (ATP) acting via P2Y1 and P2X7 receptors, likely causing
      the release of glutamate and glutamine. Mainly astrocytes responded to histamine,
      whereas the activation of muscarinic acetylcholine (ACh) receptors raised Ca(2+)
      in both cell types. Evoked neuronal and astrocytic Ca(2+) rises could last for
      several minutes without affecting mitochondrial movements or membrane potential.
      In contrast, reversible depolarization of mitochondrial membrane potential
      accompanied neuronal Ca(2+) rises induced by cyanide-evoked chemical anoxia or
      the uncoupling of mitochondrial respiration with carbonyl-cyanide-4
      (trifluoromethoxy)-phenylhydrazone (FCCP). During such metabolic perturbation,
      mitochondrial depolarization also occurred in astrocytes, whereas Ca(2+) was
      largely unaffected. In summary, fetal human cortical neurons and astrocytes show
      distinct patterns of neuro/glio-transmitter- and metabolically-evoked Ca(2+)
      rises and possess active mitochondria. One aspect of our discussion deals with
      the question of whether the functional mitochondria contribute to cellular Ca(2+)
      homeostasis that seems to be already well-developed in fetal human cortical brain
      cells. 

PMID- 23876320
TI  - Cerebrospinal fluid derived from progressive multiple sclerosis patients promotes
      neuronal and oligodendroglial differentiation of human neural precursor cells in
      vitro.
AB  - In the adult CNS, tissue-specific germinal niches, such as the subventricular
      zone of the lateral ventricles and the subgranular zone of the dentate gyrus of
      the hippocampus, contain multipotent neural precursor cells (NPCs) with the
      capacity to self-renew and differentiate into functional brain cells (i.e.
      neurons, astrocytes or oligodendrocytes). Due to their intrinsic plasticity, NPCs
      can be considered an essential part of the cellular mechanism(s) by which the CNS
      tries to repair itself after an injury. In inflammatory CNS disorders, such as
      multiple sclerosis (MS), neurogenesis and gliogenesis occur as part of an
      'intrinsic' self-repair process. However, full and long-lasting repair in
      progressive MS is not achieved. Recent data suggest that endogenous NPCs, while
      trying to repair the damaged CNS in MS, may become the target of the disease
      itself. It is possible that factors produced during MS, like CNS-infiltrating
      blood-borne inflammatory mononuclear cells, reactive CNS-resident cells, and
      humoral mediators, can alter the physiological properties of NPCs, ultimately
      impairing their ability to promote neural regeneration. Here, we investigate the
      effect of cerebrospinal fluid (CSF) derived from primary progressive (PPMS) and
      secondary progressive (SPMS) MS patients (CSF-MS) on the survival, proliferation,
      and differentiation of commercially available human embryonic-derived NPCs named
      ENStem-A. We found that PPMS derived CSF markedly reduced the proliferation of
      ENStem-A and increased their differentiation toward neuronal and oligodendroglial
      cells, compared to control CSF. Similar but less striking results were seen when
      ENstem-A were treated with SPMS derived CSF. Our findings suggest that in both
      SPMS and PPMS the CNS milieu, as determined by extrapolation from CSF findings,
      may stimulate the endogenous pool of NPCs to differentiate into neurons and
      oligodendrocytes. 

PMID- 23876321
TI  - Transitioning from genotypes to epigenotypes: why the time has come for
      medulloblastoma epigenomics.
AB  - Recent advances in genomic technologies have allowed for tremendous progress in
      our understanding of the biology underlying medulloblastoma, a malignant
      childhood brain tumor. Consensus molecular subgroups have been put forth by the
      pediatric neuro-oncology community and next-generation genomic studies have led
      to an improved description of driver genes and pathways somatically altered in
      these subgroups. In contrast to the impressive pace at which advances have been
      made at the level of the medulloblastoma genome, comparable studies of the
      epigenome have lagged behind. Complementary data yielded from genomic sequencing
      and copy number profiling have verified frequent targeting of chromatin modifiers
      in medulloblastoma, highly suggestive of prominent epigenetic deregulation in the
      disease. Past studies of DNA methylation-dependent gene silencing and microRNA
      expression analyses further support the concept of medulloblastoma as an
      epigenetic disease. In this Review, we aim to summarize the key findings of past
      reports pertaining to medulloblastoma epigenetics as well as recent and ongoing
      genomic efforts linking somatic alterations of the genome with inferred
      deregulation of the epigenome. In addition, we predict what is on the horizon for
      medulloblastoma epigenetics and how aberrant changes in the medulloblastoma
      epigenome might serve as an attractive target for future therapies. 

PMID- 23876322
TI  - Functional and effective connectivity in subthalamic local field potential
      recordings of patients with Parkinson's disease.
AB  - In Parkinson's disease (PD) levodopa-associated changes in the power and long
      range temporal correlations of beta oscillations have been demonstrated, yet the
      presence and modulation of genuine connectivity in local field potentials (LFP)
      recorded from the subthalamic nucleus (STN) remains an open question. The present
      study investigated LFP recorded bilaterally from the STN at wakeful rest in ten
      patients with PD after overnight withdrawal of levodopa (OFF) and after a single
      dose levodopa administration (ON). We utilized connectivity measures being
      insensitive to volume conduction (functional connectivity: non-zero imaginary
      part of coherency; effective connectivity: phase-slope index). We demonstrated
      the presence of neuronal interactions in the frequency range of 10-30 Hz in STN
      LFP without a preferential directionality of interactions between different
      contacts along the electrode tracks. While the direction of neuronal interactions
      per se was preserved after levodopa administration, functional connectivity and
      the ventral-dorsal information flow were modulated by medication. The OFF-ON
      differences in functional connectivity were correlated with the levodopa-induced
      improvement in clinical Unified Parkinson's Disease Rating Scale scores. We
      hypothesize that regional neuronal interactions, as reflected in STN-LFP
      connectivity, might represent a basis for the intra-nuclear spatial specificity
      of deep brain stimulation. Moreover, our results suggest the potential use of
      volume conduction-insensitive measures of connectivity in STN-LFP as a marker of
      clinical motor symptoms in PD.

PMID- 23876323
TI  - Acute caffeine administration impact on working memory-related brain activation
      and functional connectivity in the elderly: a BOLD and perfusion MRI study.
AB  - In young individuals, caffeine-mediated blockade of adenosine receptors and
      vasoconstriction has direct repercussions on task-related activations, changes in
      functional connectivity, as well as global vascular effects. To date, no study
      has explored the effect of caffeine on brain activation patterns during highly
      demanding cognitive tasks in the elderly. This prospective, placebo-controlled
      crossover design comprises 24 healthy elderly individuals (mean age 68.8 +/- 4.0
      years, 17 females) performing a 2-back working memory (WM) task in functional
      magnetic resonance imaging (fMRI). Analyses include complimentary assessment of
      task-related activations (general linear model, GLM), functional connectivity
      (tensorial independent component analysis, TICA), and baseline perfusion
      (arterial spin labeling). Despite a reduction in whole-brain global perfusion (
      22.7%), caffeine-enhanced task-related GLM activation in a local and distributed
      network is most pronounced in the bilateral striatum and to a lesser degree in
      the right middle and inferior frontal gyrus, bilateral insula, left superior and
      inferior parietal lobule as well as in the cerebellum bilaterally. TICA was
      significantly enhanced (+8.2%) in caffeine versus placebo in a distributed and
      task-relevant network including the pre-frontal cortex, the supplementary motor
      area, the ventral premotor cortex and the parietal cortex as well as the
      occipital cortex (visual stimuli) and basal ganglia. The inverse comparison of
      placebo versus caffeine had no significant difference. Activation strength of the
      task-relevant-network component correlated with response accuracy for caffeine
      yet not for placebo, indicating a selective cognitive effect of caffeine. The
      present findings suggest that acute caffeine intake enhances WM-related brain
      activation as well as functional connectivity of blood oxygen level-dependent
      fMRI in elderly individuals.

PMID- 23876324
TI  - The neural correlates of perceptual load induced attentional selection: an fMRI
      study.
AB  - The neural correlates of perceptual load induced attentional selection were
      investigated in an functional magnetic resonance imaging (fMRI) experiment in
      which attentional selection was manipulated through the variation of perceptual
      load in target search. Participants searched for a vertically or horizontally
      oriented bar among heterogeneously (the high load condition) or homogeneously
      (the low load condition) oriented distractor bars in the central display, which
      was flanked by a vertical or horizontal bar presented at the left or the right
      periphery. The search reaction times were longer when the central display was of
      high load than of low load, and were longer when the flanker was incongruent than
      congruent with the target. Importantly, the flanker congruency effect was
      manifested only in the low load condition, not in the high load condition,
      indicating that the perceptual load in target search determined whether the task
      irrelevant flanker was processed. Imaging analyses revealed a set of fronto
      parietal regions having higher activations in the high than in the low load
      condition. Anterior cingulate cortex (ACC) was more activated for the incongruent
      than for the congruent trials. Moreover, ACC and bilateral anterior insula were
      sensitive to the interaction between perceptual load and flanker congruency such
      that the activation differences between the incongruent and congruent conditions
      were significant in the low, but not in the high load condition. These results
      are consistent with the claim that ACC and bilateral anterior insula may exert
      executive control by selectively biasing processing in favor of task-relevant
      information and this biasing depends on the resources currently available to the
      control system. 

PMID- 23876325
TI  - Tracking post-error adaptation in the motor system by transcranial magnetic
      stimulation.
AB  - The commission of an error triggers cognitive control processes dedicated to
      error correction and prevention. Post-error adjustments leading to response
      slowing following an error ("post-error slowing"; PES) might be driven by changes
      in excitability of the motor regions and the corticospinal tract (CST). The time
      course of such excitability modulations of the CST leading to PES is largely
      unknown. To track these presumed excitability changes after an error, single
      pulse transcranial magnetic stimulation (TMS) was applied to the motor cortex
      ipsilateral to the responding hand, while participants were performing an Eriksen
      flanker task. A robotic arm with a movement compensation system was used to
      maintain the TMS coil in the correct position during the experiment. Magnetic
      pulses were delivered over the primary motor cortex ipsilateral to the active
      hand at different intervals (150, 300, 450 ms) after correct and erroneous
      responses, and the motor-evoked potentials (MEP) of the first dorsal interosseous
      muscle (FDI) contralateral to the stimulated hemisphere were recorded. MEP
      amplitude was increased 450 ms after the error. Two additional experiments showed
      that this increase was neither associated to the correction of the erroneous
      responses nor to the characteristics of the motor command. To the extent to which
      the excitability of the motor cortex ipsi- and contralateral to the response hand
      are inversely related, these results suggest a decrease in the excitability of
      the active motor cortex after an erroneous response. This modulation of the
      activity of the CST serves to prevent further premature and erroneous responses.
      At a more general level, the study shows the power of the TMS technique for the
      exploration of the temporal evolution of post-error adjustments within the motor
      system.

PMID- 23876326
TI  - Voltage-gated Ca2+ influx and mitochondrial Ca2+ initiate secretion from Aplysia
      neuroendocrine cells.
AB  - Neuroendocrine secretion often requires prolonged voltage-gated Ca(2+) entry;
      however, the ability of Ca(2+) from intracellular stores, such as endoplasmic
      reticulum or mitochondria, to elicit secretion is less clear. We examined this
      using the bag cell neurons, which trigger ovulation in Aplysia by releasing egg
      laying hormone (ELH) peptide. Secretion from cultured bag cell neurons was
      observed as an increase in plasma membrane capacitance following Ca(2+) influx
      evoked by a 5-Hz, 1-min train of depolarizing steps under voltage-clamp. The
      response was similar for step durations of >= 50 ms, but fell off sharply with
      shorter stimuli. The capacitance change was attenuated by replacing external
      Ca(2+) with Ba(2+), blocking Ca(2+) channels, buffering intracellular Ca(2+) with
      EGTA, disrupting synaptic protein recycling, or genetic knock-down of ELH.
      Regarding intracellular stores, liberating mitochondrial Ca(2+) with the
      protonophore, carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazone (FCCP), brought
      about an EGTA-sensitive elevation of capacitance. Conversely, no change was
      observed to Ca(2+) released from the endoplasmic reticulum or acidic stores.
      Prior exposure to FCCP lessened the train-induced capacitance increase,
      suggesting overlap in the pool of releasable vesicles. Employing GTP-gamma-S to
      interfere with endocytosis delayed recovery (presumed membrane retrieval) of the
      capacitance change following FCCP, but not the train. Finally, secretion was
      correlated with reproductive behavior, in that neurons isolated from animals
      engaged in egg-laying presented a greater train-induced capacitance elevation vs
      quiescent animals. The bag cell neuron capacitance increase is consistent with
      peptide secretion requiring high Ca(2+), either from influx or stores, and may
      reflect the all-or-none nature of reproduction.

PMID- 23876327
TI  - Movement-induced uncoupling of primary sensory and motor areas in focal task
      specific hand dystonia.
AB  - INTRODUCTION: Due to growing evidence of sensorimotor integration impairment in
      focal task-specific hand dystonia, we aimed at describing primary sensory (S1)
      and primary motor (M1) cortex source activities and their functional cross-talk
      during a non-dystonia-inducing sensorimotor task free of biases generated by the
      interfering with the occurrence of dystonic movements. METHOD:
      Magnetoencephalographic brain signals and opponens pollicis (OP)
      electromyographic activities were acquired at rest and during a simple isometric
      contraction performed either alone or in combination with median nerve
      stimulation. The task was performed separately with the right and left hand by
      eight patients suffering from focal task-specific hand dystonia and by eight
      healthy volunteers. Through an ad hoc procedure Functional Source Separation
      (FSS), distinct sources were identified in S1 (FSS1) and M1 (FSM1) devoted to
      hand control. Spectral properties and functional coupling (coherence) between the
      two sources were assessed in alpha [8,13]Hz, beta [14,32]Hz and gamma [33,45]Hz
      frequency bands. RESULTS: No differences were found between spectral properties
      of patients and controls for either FSM1 or FSS1 cerebral sources. Functional
      coupling between FSM1 and FSS1 (gamma band coherence), while comparable between
      dystonic patients and healthy controls at rest, was selectively reduced in
      patients during movement. All findings were present in both hemispheres.
      DISCUSSION: Because previous literature has shown that gamma-band sensory-motor
      synchronization reflects an efficiency index of sensory-motor integration, our
      data demonstrate that, in dystonic patients, uncoupling replaces the functional
      coupling required for efficient sensory-motor control during motor exertion. The
      presence of bi-hemispheric abnormalities in unilateral hand dystonia supports the
      presence of an endophenotypic trait.

PMID- 23876328
TI  - Chronic treatment with lithium does not improve neuromuscular phenotype in a
      mouse model of severe spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder
      caused by defective levels of the survival motor neuron (SMN) protein. SMA causes
      spinal motoneuron (MN) loss, and progressive muscle weakness and paralysis.
      Currently, there is no effective therapy to cure this disease. Although different
      strategies focused on increasing the expression of functional SMN protein have
      been assayed, numerous SMN-independent therapeutic approaches have been
      demonstrated to have potential effectiveness in improving the SMA phenotype in
      mouse models and clinical trials. Recent works have shown that compounds which
      inhibit GSK-3beta activity are effective in promoting MN survival and
      ameliorating lifespan in models of MN diseases including SMA. Taking into account
      the reported neuroprotective actions of lithium (Li) through the inhibition of
      GSK-3beta in different studies, we tested here its potential efficiency as a
      therapeutic agent in a mouse model of severe SMA (SMNDelta7 mice). We show that
      the chronic treatment with Li initiated before the appearance of disease
      symptoms, although inhibited GSK-3beta, did not improve the median survival,
      motor behavior, and spinal MN loss linked to SMA. Li administration did not
      either ameliorate the microglial and astroglial reaction in the spinal cord or
      the depletion of glutamatergic synapses on MNs observed in SMNDelta7 animals.
      Moreover, Li treatment did not mitigate muscle atrophy or calcitonin gene-related
      peptide (CGRP) downregulation in the neuromuscular junctions linked to the
      disease. However, a significant reduction in apoptotic cell death found in the
      skeletal muscle of SMA mice was observed after Li treatment. 

PMID- 23876329
TI  - Region and task-specific activation of Arc in primary motor cortex of rats
      following motor skill learning.
AB  - Motor learning requires protein synthesis within the primary motor cortex (M1).
      Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in
      M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ
      hybridization assay in adult Long-Evans rats learning a skilled reaching task
      (SRT), in rats performing reaching-like forelimb movement without learning (ACT)
      and in rats that were trained in the operant but not the motor elements of the
      task (controls). Apart from M1, Arc expression was assessed within the rostral
      motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and
      cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained
      limb were 31% higher than ipsilateral (p<0.001), 31% higher than in the
      contralateral M1 of ACT animals (p<0.001) and 48% higher than in controls
      (p<0.001). Arc mRNA expression in SRT was positively correlated with learning
      success between two sessions (r=0.52; p=0.026). For RMA, S1, ST or cerebellum no
      significant differences in Arc mRNA expression were found between hemispheres or
      across behaviors. As Arc expression has been related to different forms of
      cellular plasticity, these findings suggest a link between M1 Arc expression and
      motor skill learning in rats. 

PMID- 23876330
TI  - Evaluation of a national microbiological surveillance system to inform automated
      outbreak detection.
AB  - OBJECTIVES: Evaluate data available from a national voluntary reporting system
      and describe the data processing necessary to enable the development and
      application of outbreak detection methods in healthcare settings. METHODS:
      Evaluation was performed on an extract of data reported between March 2007 and
      May 2012. Reporting delays were calculated and analysed at the trust, regional
      and national levels. Negative binomial regression analysis was performed to
      detect any changes in laboratory reporting within this time. RESULTS: 167
      hospital laboratories have reported to the voluntary reporting system. 1,705,126
      reports were made in the five-year study period. There is large variation in how
      laboratories report to the system. Under half (44.9%) report in a timely manner,
      with >90% of infections reported within three weeks of the specimen date.
      Overall, there was a significant increase of 17.5% in reporting after October
      2010 (95% CI 13.8-21.4%, p < 0.001) and an improvement in reporting delay, when
      new statutory reporting regulations were introduced. CONCLUSIONS: The outbreak
      detection algorithm used at the national and regional level requires further
      modification to optimise outbreak detection for individual hospitals. For any
      prospective outbreak detection system to perform optimally it is imperative that
      laboratories ensure that the data they submit is complete, consistent and timely.

PMID- 23876331
TI  - High prevalence of the epidemic Clostridium difficile PCR ribotype 078 in Iberian
      free-range pigs.
AB  - Previous studies in intensively raised piglets have detected a high prevalence of
      the epidemic Clostridium difficile PCR ribotype 078. In this article we present a
      longitudinal survey of C. difficile colonisation in a population of Iberian pigs
      reared under a free-range system. A total of 160 faecal samples from 20 piglets
      belonging to different litters were obtained by weekly sampling. C. difficile was
      recovered from samples collected at different times throughout the survey from a
      90% of piglets, resulting in an overall prevalence of 25.6% in the studied
      samples. Most positive samples (75.6%) came from <= 15-day animals, but some
      piglets shed C. difficile even on day +50. All isolates were ribotype 078,
      harboured toxin-encoding genes and showed in vitro resistance to several
      fluoroquinolones. A majority of isolates (80.5%) were also high-level resistant
      to ertapenem, and four metronidazole heteroresistant isolates (9.8%) were
      detected. In conclusion, Iberian free-range pigs can be a potential reservoir of
      epidemic antimicrobial-resistant strains of C. difficile, showing a prevalence
      rate similar to that found for intensively raised animals.

PMID- 23876332
TI  - Tail docking and the rearing of heavy pigs: the role played by gender and the
      presence of straw in the control of tail biting. Blood parameters, behaviour and
      skin lesions.
AB  - This study evaluated whether the specific heavy pig rearing context allowed the
      fattening of undocked pigs without an outbreak of tail biting. At the same time,
      gender and straw availability (small amounts) were considered to understand their
      possible interactions with tail presence in the display of tail biting. A 2 * 2 *
      2 factorial design was adopted to test the effects of these factors on blood
      parameters, behaviour and tail/ear lesions. Few interactions among factors were
      detected. Undocked pigs showed lower cortisol (P<0.02), lying behaviour
      (P<0.001), and higher risk of tail/ear biting (weeks 3 and 9), but lower risk of
      tail lesions (week 14). Straw increased the motivation for exploring (P<0.001),
      reduced serum haptoglobin (P<0.001) and the risk for tail biting (weeks 3, 9, 18)
      and ear biting (weeks 3, 9). Results highlight the importance of straw as an
      environmental enrichment and seem to indicate that fattening undocked heavy pigs
      is possible.

PMID- 23876333
TI  - Pathogenicity of Clinostomum complanatum (Digenea: Clinostomidae) in piscivorous
      birds.
AB  - The present study is focused on the pathogenicity of a parasitic digenea,
      Clinostomum complanatum among dead piscivorous birds, collected after mass
      mortalities in northern Iran. A total of 126 birds (15 species) were examined for
      parasitic infections. Birds of four species belong to the family Ardeidae were
      found to be infected with immature and mature worms. C. complanatum was more
      prevalent in Ardea purpurea followed by Nycticorax nycticorax, Egretta alba and
      Egretta garzetta. Pathological study revealed acute inflammation of the submucosa
      of the oral cavity and oesophagus which can lead to impairment of deglutition and
      malnutrition which in turn can weaken the immune system. Immature parasites were
      found to penetrate the tissues sometimes to muscular layer but adults were seen
      attached to the oral cavity and the lumen side of the oesophagus suggesting
      parasite goes through a tissue migration after infecting the definitive host and
      prior to adult stage. 

PMID- 23876334
TI  - Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan
      sulfate levels.
AB  - Mucopolysaccharidosis IVA (MPS IVA) is caused by deficiency of N
      acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to systemic skeletal
      dysplasia because of excessive storage of keratan sulfate (KS) in chondrocytes.
      In an effort to determine a precise prognosis and personalized treatment, we aim
      to characterize clinical, biochemical, and molecular findings in MPS IVA
      patients, and to seek correlations between genotype, phenotype, and blood and
      urine KS levels. Mutation screening of GALNS gene was performed in 55 MPS IVA
      patients (severe: 36, attenuated: 13, undefined: 6) by genomic PCR followed by
      direct sequence analysis. Plasma and urine KS levels were measured by ELISA
      method. Genotype/phenotype/KS correlations were assessed when data were
      available. Fifty-three different mutations including 19 novel ones (41 missense,
      2 nonsense, 4 small deletions, 1 insertion, and 5 splice-site) were identified in
      55 patients and accounted for 93.6% of the analyzed mutant alleles. Thirty-nine
      mutations were associated with a severe phenotype and ten mutations with an
      attenuated one. Blood and urine KS concentrations in MPS IVA patients were age
      dependent and markedly higher than those in age-matched normal controls. Plasma
      and urine KS levels in MPS IVA patients with the severe phenotype were higher
      than in those with an attenuated form. This study provides evidence for extensive
      allelic heterogeneity of MPS IVA. Accumulation of mutations as well as clinical
      descriptions and KS levels allows us to predict clinical severity more precisely
      and should be used for evaluation of responses to potential treatment options. 

PMID- 23876336
TI  - In vitro activity of sitafloxacin against carbapenem-resistant Acinetobacter
      baumannii.

PMID- 23876335
TI  - Pharmacokinetics of moxifloxacin in critically ill patients with impaired renal
      function undergoing pulse high-volume haemofiltration.
AB  - Moxifloxacin is an 8-methoxy quinolone with a broad spectrum of activity against
      clinically important pathogens. The aim of this study was to investigate the
      pharmacokinetics of intravenous (i.v.) moxifloxacin in critically ill patients
      with impaired renal function undergoing pulse high-volume haemofiltration (PHVHF)
      (n=8) to provide a reference for clinical rational moxifloxacin use in these
      patients. Blood and ultrafiltrate samples were obtained following i.v. infusion
      of a single 400 mg moxifloxacin dose. Concentrations of moxifloxacin in serum and
      ultrafiltrate were determined by HPLC analysis with fluorometric detection.
      Pharmacokinetics of moxifloxacin in plasma and ultrafiltrate were best described
      by a two-compartment model. Peak and trough serum moxifloxacin concentrations
      were 4.84 +/- 1.85 mg/L and 1.17 +/- 0.73 mg/L, respectively, at the arterial
      port after a single i.v. 400 mg dose. The mean elimination half-life was 4.82 +/-
      2.13 h, the volume of distribution was 82.63 +/- 24.69 L and the calculated AUC(0
      12) was 26.91 +/- 10.96 mgh/L. Total clearance was 14.36 +/- 8.44 L/h and the
      clearance of haemofiltration was 1.67 +/- 0.95 L/h.C(max)/MIC(90) ratios and
      predicted AUC(0-24)/MIC(90) ratios were above the cut-off points for common
      pathogens that indicate clinical success. A single 400 mg i.v. dose of
      moxifloxacin is safe and efficacious in the treatment of critically ill patients
      infected with clinically common pathogens and impaired renal function undergoing
      PHVHF. It also should be kept in mind that the standard dose is not sufficient
      for this population infected with pathogens with a higher MIC(90) (0.5 mg/L).

PMID- 23876337
TI  - Tocopheramines and tocotrienamines as antioxidants: ESR spectroscopy, rapid
      kinetics and DFT calculations.
AB  - Tocopheramines (TNH2) and tocotrienamines (T3NH2) are analogues of tocopherols
      (TOH) and tocotrienols in which phenolic OH is replaced by NH2. It was shown in
      previous studies that TNH2 and T3NH2 act as potent antioxidants. In this study we
      compared the one-electron oxidation of TNH2/T3NH2 by diphenyl picryl hydrazyl
      (DPPH) and galvinoxyl (GOX) radicals with the one of alpha-TOH as a reference
      compound using ESR spectroscopy, stopped flow spectrophotometry and density
      functional theory (DFT) calculations. ESR spectroscopy revealed the presence of
      tocopheramine radicals during electrochemical oxidation of alpha-TNH2. Kinetic
      measurements demonstrated that in apolar n-hexane TNH2/T3NH2 derivatives reacted
      two to three orders of magnitude slower than alpha-TOH with the model radicals.
      DFT calculations indicated that this correlates well with the higher bond
      dissociation energy (BDE) for N-H in TNH2 than for O-H in alpha-TOH in pure H
      atom transfer (HAT). In the more polar medium ethanol TNH2/T3NH2 derivatives
      partially reacted faster than alpha-TOH depending on the reaction partner. DFT
      calculations suggest that this is due to reaction mechanisms alternative to HAT.
      According to thermochemistry data sequential proton loss and electron transfer
      (SPLET) is more favored for alpha-TOH in ethanol than for TNH2. Therefore, for
      TNH2 a contribution of the alternative mechanism of sequential electron transfer
      proton transfer (SET-PT) could be a possible explanation. These data show that
      the antioxidant reactivity strongly depends on the structure, reaction partners
      and environment. According to these findings TNH2/T3NH2 should be superior as
      antioxidants over alpha-TOH in polar head group regions of membranes but not in
      the apolar core of lipid bilayers. 

PMID- 23876338
TI  - Design, synthesis and in vitro evaluation against human cancer cells of 5-methyl
      5-styryl-2,5-dihydrofuran-2-ones, a new series of goniothalamin analogues.
AB  - The present work describes the preparation of a novel series of compounds based
      on the structure of goniothalamin (1), a natural styryl lactone with known
      cytotoxic and antiproliferative activities against a variety of cancer cell
      lines. A focused library of 17 goniothalamin analogues displaying the 5-methyl
      2,5-dihydrofuran-2-one motif were prepared, and their cytotoxicity evaluated.
      While the analogues bearing methoxy and/or hydroxy groups on the aromatic moiety
      usually were at least three times less potent than the lead compound (1), ortho
      and para-trifluoromethyl analogues 10 and 11 exhibited levels of cytotoxicity
      similar to goniothalamin (1) against most cancer cell lines evaluated. One could
      suggest that the electronic effect of the trifluoromethyl group activates the
      inhibitor's electrophilic site via reduction of the electron density of the
      alpha,beta-unsaturated ester oxygen atom. These results provide new information
      on the structure activity relationship of these alpha,beta-unsaturated styryl
      lactones, thereby further focusing the design of novel candidates. 

PMID- 23876339
TI  - Structure-activity relationships for ketamine esters as short-acting
      anaesthetics.
AB  - A series of aliphatic esters of the non-opioid anaesthetic/analgesic ketamine
      were prepared and their properties as shorter-acting analogues of ketamine itself
      were explored in an infused rat model, measuring the time after infusion to
      recover from both the anaesthetic (righting reflex) and analgesic (response to
      stimulus) effects. The potency of the esters as sedatives was not significantly
      related to chain length, but Me, Et and i-Pr esters were the more dose potent (up
      to twofold less than ketamine), whereas n-Pr esters were less potent (from 2- to
      6-fold less than ketamine). For the Me, Et and i-Pr esters recovery from
      anaesthesia was 10-15-fold faster than from ketamine itself, and for the n-Pr
      esters it was 20-25-fold faster than from ketamine. A new dimethylamino ketamine
      derivative (homoketamine) had ketamine-like sedative effects but was slightly
      less potent than, but ester analogues of homoketamine had very weak sedative
      effects. 

PMID- 23876340
TI  - Antiplatelet effect of AMP-activated protein kinase activator and its
      potentiation by the phosphodiesterase inhibitor dipyridamole.
AB  - AMP-activated protein kinase (AMPK) activates endothelial nitric oxide synthase
      (eNOS) via phosphorylation at the activating site. The eNOS-nitric oxide
      (NO)/soluble guanylate cyclase (sGC)-cGMP/cGMP-dependent protein kinase (PKG)
      signaling axis is a major antiaggregatory mechanism residing in platelets. Based
      on the hypothesis that direct activation of AMPK might be a potential strategy to
      inhibit platelet aggregation, the antiplatelet effect of AMPK activators was
      investigated. Treatment of isolated platelets with the AMPK activator, 5
      aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) resulted in AMPK
      activation and a decrease in aggregation, which was abolished by pretreatment
      with the AMPK inhibitors compound C (CC) and ara-A. Such an AMPK-dependent
      antiaggregatory effect was also observed with other AMPK activators such as A
      769662 and PT1. AICAR induced eNOS activation was followed by NO synthesis, cGMP
      production, and subsequent phosphorylation of vasodilator-stimulated
      phosphoprotein (VASP), a PKG substrate. All these events were blocked by CC or
      ara-A pretreatment, and each event was inhibited by the eNOS inhibitor L-NAME,
      the sGC inhibitor ODQ, and the PKG inhibitor Rp-8-pCPT-cGMPS. Simultaneous
      treatment of dipyridamole, a phosphodiesterase (PDE) inhibitor, with AICAR
      potentiated the antiaggregatory effect by enhancing the cGMP elevation.
      Administration of AICAR increased platelet cGMP and prolonged FeCl3-induced
      arterial occlusion time in rats, which further increased in combination with
      dipyridamole. In conclusion, AMPK activators inhibited platelet aggregation by
      stimulating the eNOS-NO/sGC-cGMP/PKG signaling pathway. The antiplatelet effect
      of AMPK activators could be potentiated in combination with a PDE inhibitor
      through the common mechanism of elevating cGMP. Thus, AMPK may serve as a
      potential target for antiplatelet therapy. 

PMID- 23876341
TI  - Role of organic cation transporter OCT2 and multidrug and toxin extrusion
      proteins MATE1 and MATE2-K for transport and drug interactions of the antiviral
      lamivudine.
AB  - The antiviral lamivudine is cleared predominantly by the kidney with a relevant
      contribution of renal tubular secretion. It is not clear which drug transporters
      mediate lamivudine renal secretion. Our aim was to investigate lamivudine as
      substrate of the renal drug transporters organic cation transporter 2 (OCT2) and
      multidrug and toxin extrusion proteins MATE1 and MATE2-K. Uptake experiments were
      performed in OCT2, MATE1, or MATE2-K single-transfected human embryonic kidney
      293 (HEK) cells. Transcellular transport experiments were performed in OCT2
      and/or MATE1 single- or double-transfected Madin-Darby canine kidney II (MDCK)
      cells grown on transwell filters. Lamivudine uptake was significantly increased
      in HEK-OCT2, HEK-MATE1, and HEK-MATE2-K cells compared to control cells. In
      transcellular experiments, OCT2 located in the basolateral membrane had no effect
      on transcellular lamivudine transport. MATE1 located in the apical membrane
      decreased intracellular concentrations and increased transcellular transport of
      lamivudine from the basal to the apical compartment. MATE1- or MATE2-K-mediated
      transport was increased by an oppositely directed pH gradient. Several
      simultaneously administered drugs inhibited OCT2- or MATE2-K-mediated lamivudine
      uptake. The strongest inhibitors were carvedilol for OCT2 and trimethoprim for
      MATE2-K (inhibition by 96.3 and 83.7% at 15 MUM, respectively, p<0.001).
      Trimethoprim inhibited OCT2- and MATE2-K-mediated lamivudine uptake with IC50
      values of 13.2 and 0.66 MUM, respectively. Transcellular lamivudine transport in
      OCT2-MATE1 double-transfected cells was inhibited by trimethoprim with an IC50
      value of 6.9 MUM. Lamivudine is a substrate of renal drug transporters OCT2,
      MATE1, and MATE2-K. Concomitant administration of drugs that inhibit these
      transporters could decrease renal clearance of lamivudine.

PMID- 23876343
TI  - The photosensitizer disulfonated aluminum phthalocyanine reduces uptake and
      alters trafficking of fluid phase endocytosed drugs in vascular endothelial cells
      -impact on efficacy of photochemical internalization.
AB  - Targeting cancer vasculature is an emerging field in cancer treatment.
      Photochemical internalization (PCI) is a drug delivery technology based on
      photochemical lysis of drug-bearing endocytic vesicles originally designed to
      target cancer cells. Recent investigations have revealed a lower PCI efficacy in
      vascular endothelial cells (HUVECs) in vitro than in HT1080 fibrosarcoma cells.
      This manuscript aims to explore the limiting factor for the PCI effect in HUVECs.
      Cellular uptake of the photosensitizers AlPcS(2a) and TPPS(2a), and a model
      compound for macromolecular drugs taken up by fluid phase endocytosis, Alexa488
      dextran, was explored by flow cytometry. The uptake of AlPcS(2a) and TPPS(2a) was
      3.8-fold and 37-fold higher in HUVECs than in HT1080 cells, respectively, while
      the Alexa488-dextran uptake was 50% lower. AlPcS(2a) (but not TPPS(2a)) was shown
      to reduce Alexa488-dextran uptake in a concentration-dependent manner, resulting
      in 66% and 33% attenuation of Alexa488-dextran uptake at 20 MUg/ml AlPcS(2a) in
      HUVECs and HT1080 cells respectively. Studies of intracellular localization of
      Alexa488-dextran and AlPcS(2a) by confocal microscopy in HUVECs uncovered a
      concentration-dependent AlPcS(2a)-induced inhibition of Alexa488-dextran
      trafficking into AlPcS(2a)-stained and acidic vesicles. The localization of
      Alexa488-dextran to AlPcS(2a)-localizing compartments was reduced by 40% when the
      AlPcS(2a) concentration was increased from 5 to 20 MUg/ml. The treatment dose of
      AlPcS(2a) was found to influence on the efficacy of PCI of saporin, but to a
      lesser extent than expected considering the data from cellular uptake and
      intracellular trafficking of Alexa488-dextran. The implications of these results
      for further development of vascular targeting-PCI are discussed.

PMID- 23876342
TI  - Role of hepatic resident and infiltrating macrophages in liver repair after acute
      injury.
AB  - Treatment of liver disease, caused by hepatotoxins, viral infections, alcohol
      ingestion, or autoimmune conditions, remains challenging and costly. The liver
      has a powerful capacity to repair and regenerate, thus a thorough understanding
      of this tightly orchestrated process will undoubtedly improve clinical means of
      restoring liver function after injury. Using a murine model of acute liver injury
      caused by overdose of acetaminophen (APAP), our studies demonstrated that the
      combined absence of liver resident macrophages (Kupffer cells, KCs), and
      infiltrating macrophages (IMs) resulted in a marked delay in liver repair, even
      though the initiation and extent of peak liver injury was not impacted. This
      delay was not due to impaired hepatocyte proliferation but rather prolonged
      vascular leakage, which is caused by APAP-induced liver sinusoidal endothelial
      cell (LSEC) injury. We also found that KCs and IMs express an array of angiogenic
      factors and induce LSEC proliferation and migration. Our mechanistic studies
      suggest that hypoxia-inducible factor (HIF) may be involved in regulating the
      angiogenic effect of hepatic macrophages (Macs), as we found that APAP challenge
      resulted in hypoxia and stabilization of HIF in the liver and hepatic Macs.
      Together, these data indicate an important role for hepatic Macs in liver blood
      vessel repair, thereby contributing to tissue recovery from acute injury. 

PMID- 23876344
TI  - Dancing with chemical formulae of antivirals: a personal account.
AB  - A chemical structure is a joy forever, and this is how I perceived the chemical
      structures of a number of antiviral compounds with which I have been personally
      acquainted over the past 3 decades: (1) amino acid esters of acyclovir (i.e.
      valaciclovir); (2) 5-substituted 2'-deoxyuridines (i.e. brivudin); (3) 2',3'
      dideoxynucleoside analogues (i.e. stavudine); (4) acyclic nucleoside phosphonates
      (ANPs) (i.e. cidofovir, adefovir); (5) tenofovir disoproxil fumarate (TDF) and
      drug combinations therewith; (6) tenofovir alafenamide (TAF, GS-7340), a new
      phosphonoamidate prodrug of tenofovir; (7) pro-prodrugs of PMEG (i.e. GS-9191 and
      GS-9219); (8) new ANPs: O-DAPy and 5-aza-C phosphonates; (9) non-nucleoside
      reverse transcriptase inhibitors (NNRTIs): HEPT and TIBO derivatives; and (10)
      bicyclam derivatives (i.e. AMD3100). 

PMID- 23876346
TI  - Five-year risk of end-stage renal disease among intensive care patients surviving
      dialysis-requiring acute kidney injury: a nationwide cohort study.
AB  - INTRODUCTION: Dialysis-requiring acute kidney injury (D-AKI) is common among
      intensive care unit (ICU) patients. However, follow-up data on the risk of end
      stage renal disease (ESRD) among these patients remain sparse. We assessed the
      short-term and long-term risk of ESRD after D-AKI, compared it with the risk in
      other ICU patients, and examined the risk within subgroups of ICU patients.
      METHODS: We used population-based medical registries to identify all adult
      patients admitted to an ICU in Denmark from 2005 through 2010, who survived for
      90 days after ICU admission. D-AKI was defined as needing acute dialysis at or
      after ICU admission. Subsequent ESRD was defined as a need for chronic dialysis
      for more than 90 days or a kidney transplant. We computed the cumulative ESRD
      risk for patients with D-AKI and for other ICU patients, taking into account
      death as a competing risk, and computed hazard ratios (HRs) using a Cox model
      adjusted for potential confounders. RESULTS: We identified 107,937 patients who
      survived for 90 days after ICU admission. Of these, 3,062 (2.8%) had an episode
      of D-AKI following ICU admission. The subsequent risk of ESRD up to 180 days
      after ICU admission was 8.5% for patients with D-AKI, compared with 0.1% for
      other ICU patients. This corresponds to an adjusted HR of 105.6 (95% confidence
      interval (CI): 78.1 to 142.9). Among patients who survived 180 days after ICU
      admission without developing ESRD (n = 103,996), the 181-day to 5-year ESRD risk
      was 3.8% for patients with D-AKI, compared with 0.3% for other ICU patients,
      corresponding to an adjusted HR of 6.2 (95% CI: 4.7 to 8.1). During the latter
      period, the impact of AKI was most pronounced in the youngest patients, aged 15
      to 49 years (adjusted HR = 12.8, 95% CI: 6.5 to 25.4) and among patients without
      preexisting chronic kidney disease (adjusted HR = 11.9, 95% CI: 8.5 to 16.8).
      CONCLUSION: D-AKI is an important risk factor for ESRD for up to five years after
      ICU admission.

PMID- 23876347
TI  - Assessment of L-arginine asymmetric 1 dimethyl (ADMA) in early-onset and late
      onset (severe) preeclampsia.
AB  - Preeclampsia (PE) is characterized by hypertension and proteinuria. It has been
      classified in early or late according to gestational age at the onset of disease.
      Endothelial dysfunction plays a crucial part in its pathogenesis. NO is a potent
      vasodilator and ADMA is its endogenous inhibitor. We have assessed maternal ADMA
      levels. ADMA were increased in early [0.66 MUmol/L] versus late sPE [0.47
      MUmol/L] (P=0.001) and versus normotensive pregnant [0.48 MUmol/L] (P=0.001). Our
      findings suggest that high ADMA levels in early sPE could compromise NO synthesis
      contributing to endothelial dysfunction, leading to impaired placentation and the
      onset of this disease.

PMID- 23876348
TI  - Simvastatin treatment increases nitrite levels in obese women: modulation by T(
      786)C polymorphism of eNOS.
AB  - OBJECTIVE AND SUBJECTS: Evidence indicates an impairment of nitric oxide (NO) in
      obesity. Statins present pleiotropic effects independently of cholesterol
      lowering, including increasing of eNOS expression and antioxidant effects. We
      evaluated the effects of simvastatin treatment at 45 days on circulating nitrite
      (NO marker) and TBARS-MDA levels in obese women without comorbidities
      (hypertension, diabetes and dyslipidemia). Moreover, we verified whether obese
      women carrying the C variant of T(-786)C polymorphism located in eNOS may have
      increased levels of nitrite after treatment compared to TT genotype. RESULTS:
      After simvastatin treatment, while the plasma nitrite levels increased 42%
      (P=0.0008), the TBARS-MDA levels reduced 58% (P=0.0069). We observed increased
      levels of nitrite in both groups of genotypes (TT vs. TC+CC); however, rise in C
      allele carriers was 60% comparing with 44% in TT. CONCLUSION: Our results
      demonstrated a restoration of nitrite levels in obese women treated with
      simvastatin, which is modulated by T(-786)C polymorphism.

PMID- 23876349
TI  - Redox conversions of dinitrosyl iron complexes with natural thiol-containing
      ligands.
AB  - Using the electron paramagnetic resonance (EPR) and optical spectrophotometric
      methods, it has been established that biologically active, water-soluble
      dinitrosyl iron complexes (DNIC) with glutathione are predominantly represented
      by the diamagnetic binuclear form (B-DNIC) even in the presence of a 10-fold
      excess of glutathione non-incorporated into DNIC at neutral pH. With the increase
      in rN to 10-11, B-DNIC are fully converted into the paramagnetic mononuclear form
      (M-DNIC) with a characteristic EPR signal at g?=2.04, g||=2.014 and gaver.=2.03.
      After treatment with a strong reducing agent sodium dithionite, both M- and B
      DNIC are converted into the paramagnetic form with a characteristic EPR signal at
      g?=2.01, g||=1.97 and gaver.=2.0. Both forms display similar absorption spectra
      with absorption bands at 960 and 640nm and a bend at 450nm. After oxidation by
      atmospheric oxygen, this situation is reversed, which manifests itself in the
      disappearance of the EPR signal at gaver.=2.0 and complete regeneration of
      initial absorption spectra of M- or B-DNIC with characteristic absorption bands
      at 390 or 360 and 310nm, respectively. Treatment of bovine serum albumin (BSA)
      solutions with gaseous NO in the presence of Fe(2+) and cysteine yields BSA-bound
      M-DNIC (M-DNIC-BSA). After treatment with sodium dithionite, the latter undergo
      transformations similar to those established for low-molecular M-DNIC with
      glutathione. Based on the complete coincidence of the optical and the EPR
      characteristics of sodium dithionite-treated M- and B-DNIC and other findings, it
      is suggested that sodium dithionite-reduced B-DNIC are subject to reversible
      decomposition into M-DNIC. The reduction and subsequent oxidation of M- and B
      DNIC are interpreted in the paradigm of the current concepts of the initial
      electronic configurations of M- and B-DNIC (d(7) ({Fe(NO)2}(7)) and d(7)-d(7)
      ({Fe(NO)2}(7)-{Fe(NO)2}(7)), respectively). 

PMID- 23876350
TI  - Benign hepatocellular nodules: what have we learned using the patho-molecular
      classification.
AB  - Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign
      hepatocellular tumors that develop most frequently in females and in non
      cirrhotic livers. HCA are prone to bleed and to transform into hepatocellular
      carcinoma (HCC). Four major subgroups of HCA have been thus far identified:
      HNF1alpha mutated HCA, inflammatory HCA (IHCA), beta-catenin mutated HCA (b-HCA
      and b-IHCA), based on mutations in specific oncogenes and tumor suppressors. B
      HCA and b-IHCA are strongly associated with HCC transformation. Benign
      hepatocellular tumors can be classified using immunohistochemistry (LFABP, CRP,
      GS, b-catenin). Analysis of HCA phenotypes has led to the identification of
      patients at risk of HCC transformation and therefore improved the indications
      provided by invasive and non-invasive diagnostic techniques, such as biopsies and
      MRI. These recent advances have broadened the clinical scope of HCA in various
      conditions, such as their presence in males, in obese patients, in patients
      suffering from liver vascular disorders, genetic diseases. However, specific
      immunohistochemistry has shown limitations particularly for the identification of
      b-HCA, thereby, outlining the importance of molecular studies to improve the
      diagnosis/prognosis of HCA. If evaluation of prognosis and treatment has
      benefited from these advances, much more needs to be done to obtain guidelines
      for good clinical practice. 

PMID- 23876351
TI  - Diagnostic and clinical significance of anti-centromere antibodies in primary
      biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune disease of the liver
      characterised by biochemical evidence of cholestasis, elevated alkaline
      phosphatase levels and the presence of the highly disease specific anti
      mitochondrial autoantibodies. Extra-hepatic autoimmune manifestations are common,
      including rheumatic disorders, such as systemic sclerosis (SSc). Notably, PBC is
      the most frequent autoimmune liver disease in SSc patients. Based on skin lesion
      extension, two major SSc disease subgroups are recognised: limited cutaneous SSc
      (lSSc) and diffuse cutaneous SSc. Anti-centromere antibody (ACA) positivity is
      highly characteristic of SSc, with up to 90% prevalence in lSSc patients. ACA has
      also been found in up to 30% of PBC patients and 80% of patients with a PBC/SSc
      overlap syndrome. The diagnostic and clinical significance of ACA positivity in
      patients with PBC without SSc has recently been under investigation, with several
      studies highlighting links to severe bile duct injury and portal hypertension.
      This review discusses the diagnostic and clinical relevance of ACA in patients
      with PBC, with or without SSc. 

PMID- 23876352
TI  - Ultrasound elastography in the head and neck. Part I. Basic principles and
      practical aspects.
AB  - Ultrasound elastography (USE) is a rapidly developing field of imaging that
      measures and displays tissue elasticity or stiffness properties using ultrasound.
      In recent years, real-time USE modes have appeared on commercially available
      clinical ultrasound machines, stimulating an explosion of research into potential
      oncologic and non-oncologic clinical applications of USE. Preliminary evidence
      suggests that USE can differentiate benign and malignant conditions accurately in
      several different tissues. This article presents an overview of the basic
      principles of different USE technologies that are currently under investigation
      in the head and neck region. In addition, more practical aspects pertaining to
      the optimal performance of USE at this site are discussed. 

PMID- 23876353
TI  - First report of a sequence type 239 vancomycin-intermediate Staphylococcus aureus
      isolate in Mainland China.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen that
      causes a wide range of both hospital- and community-acquired infections. The high
      prevalence of MRSA and the extensive use of vancomycin in Mainland China may lead
      to the emergence of vancomycin-intermediate S. aureus (VISA) isolates. In this
      case, we report a VISA isolate from a 34-year-old male patient with steam burn.
      The isolate was determined to be sequence type 239 staphylococcal cassette
      chromosome mec type III, the most prevalent MRSA clone in Mainland China. 

PMID- 23876354
TI  - Novel G10P[14] rotavirus strain, northern territory, Australia.
AB  - We identified a genotype G10P[14] rotavirus strain in 5 children and 1 adult with
      acute gastroenteritis from the Northern Territory, Australia. Full genome
      sequence analysis identified an artiodactyl-like (bovine, ovine, and camelid) G10
      P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3 genome constellation. This finding suggests
      artiodactyl-to-human transmission and strengthens the need to continue rotavirus
      strain surveillance. 

PMID- 23876345
TI  - Potential substrates for nicotine and alcohol interactions: a focus on the
      mesocorticolimbic dopamine system.
AB  - Epidemiological studies consistently find correlations between nicotine and
      alcohol use, yet the neural mechanisms underlying their interaction remain
      largely unknown. Nicotine and alcohol (i.e., ethanol) share many common molecular
      and cellular targets that provide potential substrates for nicotine-alcohol
      interactions. These targets for interaction often converge upon the
      mesocorticolimbic dopamine system, where the link to drug self-administration and
      reinforcement is well documented. Both nicotine and alcohol activate the
      mesocorticolimbic dopamine system, producing downstream dopamine signals that
      promote the drug reinforcement process. While nicotine primarily acts via
      nicotinic acetylcholine receptors, alcohol acts upon a wider range of receptors
      and molecular substrates. The complex pharmacological profile of these two drugs
      generates overlapping responses that ultimately intersect within the
      mesocorticolimbic dopamine system to promote drug use. Here we will examine
      overlapping targets between nicotine and alcohol and provide evidence for their
      interaction. Based on the existing literature, we will also propose some
      potential targets that have yet to be directly tested. Mechanistic studies that
      examine nicotine-alcohol interactions would ultimately improve our understanding
      of the factors that contribute to the associations between nicotine and alcohol
      use. 

PMID- 23876359
TI  - Evaluation of the effectiveness of the external nasal dilator strip in adolescent
      athletes: a randomized trial.
AB  - OBJECTIVES: Evaluate the cardio-respiratory capacity (VO2max.) and peak nasal
      inspiratory flow (PNIF) of healthy adolescent athletes with experimental and
      placebo external nasal dilator strips (ENDS). METHODS: 48 healthy adolescent
      athletes between the ages of 11 and 15 were evaluated and submitted to a cardio
      respiratory 1000 m race in randomized order. The participants had peak nasal
      inspiratory flow (PNIF) values measured using the In-check-inspiratory flow
      meter. Dyspnea intensity was evaluated after a 1000 m test race using a labeled
      visual analog scale for dyspnea. RESULTS: In relation to VO2max., when the
      participants used the experimental ENDS, significantly higher means were noted
      than when the placebo was used (53.0 +/- 4.2 mL/kg min(-1) and 51.2 +/- 5.5 mL/kg
      min(-1), respectively) (p<0.05). In relation to PNIF, there was a statistically
      significant difference between the experimental and placebo ENDS result, that
      being, 123 +/- 38 L/min and 116 +/- 38 L/min, respectively (p<0.05). The dyspnea
      perceived by the participants was representatively lesser in the experimental
      ENDS condition compared to the placebo after the cardio-respiratory test
      (p<0.05). CONCLUSIONS: The results suggest that the ENDS improve maximal oxygen
      uptake, nasal patency and respiratory effort in healthy adolescent athletes after
      submaximal exercise.

PMID- 23876358
TI  - CT- and MRI-based seed localization in postimplant evaluation after prostate
      brachytherapy.
AB  - PURPOSE: To compare the uncertainties in CT- and MRI-based seed reconstruction in
      postimplant evaluation after prostate seed brachytherapy in terms of
      interobserver variability and quantify the impact of seed detection variability
      on a selection of dosimetric parameters for three postplan techniques: (1) CT,
      (2) MRI-T1 weighted fused with MRI-T2 weighted, and (3) CT fused with MRI-T2
      weighted. METHODS AND MATERIALS: Seven physicists reconstructed the seed
      positions on postimplant CT and MRI-T1 images of three patients. For each patient
      and imaging modality, the interobserver variability was calculated with respect
      to a reference seed set. The effect of this variability on dosimetry was
      calculated for CT and CT + MRI-T2 (CT-based seed reconstruction), as well as for
      MRI-T1 + MRI-T2 (MRI-T1-based seed reconstruction), using fixed CT and MRI-T2
      prostate contours. RESULTS: Averaged over three patients, the interobserver
      variability in CT-based seed reconstruction was 1.1 mm (1 SDref, i.e., standard
      deviation with respect to the reference value). The D90 (dose delivered to 90% of
      the target) variability was 1.5% and 1.3% (1 SDref) for CT and CT + MRI-T2,
      respectively. The mean interobserver variability in MRI-based seed reconstruction
      was 3.0 mm (1 SDref), and the impact of this variability on D90 was 6.6% for MRI
      T1 + MRI-T2. CONCLUSIONS: Seed reconstruction on MRI-T1-weighted images was less
      accurate than on CT. This difference in uncertainties should be weighted against
      uncertainties due to contouring and image fusion when comparing the overall
      reliability of postplan techniques.

PMID- 23876360
TI  - Letter to the Editor regarding 'Germ-cell tumors of the Eustachian tube: a
      necessary update'.

PMID- 23876361
TI  - MAL2 expression predicts distant metastasis and short survival in pancreatic
      cancer.
AB  - BACKGROUND: Pancreatic cancer is associated with a devastating prognosis,
      partially because of its aggressive metastatic ability. Identification of
      prognostic markers of metastasis would be useful in the clinical management of
      postoperative patients with pancreatic cancer. Mal, T-cell differentiation
      protein 2 (MAL2) has been identified as a molecule predictive of metastases; the
      clinical relevance of MAL2 in pancreatic cancer is unknown. METHODS: Orthotopic
      human pancreatic cancer xenografts from the pancreatic cancer cell line SUIT-2
      were established in nude mice. Only liver metastasis was harvested and cultured.
      These metastatic cycles were repeated 5 times to establish a highly metastatic
      cell line, termed metastatic SUIT-2 (MS). We investigated proliferation and
      motility of MS cells compared with those of the parent SUIT-2. Microarray
      analysis was performed to investigate differences in gene expression. We also
      performed immunohistochemical analysis of 89 formalin-fixed, paraffin-embedded
      human pancreatic cancer tissue samples to investigate the clinical significance
      of MAL2 expression. RESULTS: MS cells showed a greater metastatic rate after
      orthotopic implantation than parental SUIT-2. MS cells had increased motility but
      decreased proliferation compared with parental SUIT-2. Microarray analyses showed
      that 26 genes were significantly upregulated (>10-fold) in MS cells compared with
      parental SUIT-2, particularly MAL2 expression. Immunohistochemical analysis
      showed that high expression of MAL2 was associated with a lesser survival of
      postoperative patients (P = .03) and a high rate of distant metastasis (P =
      .008). CONCLUSION: We characterized a newly established pancreatic cancer cell
      line with highly metastatic potential. MAL2 is a promising predictive marker for
      distant metastasis and short survival in patients with resected pancreatic
      cancer.

PMID- 23876362
TI  - Intraoperative crystalloid overload leads to substantial inflammatory
      infiltration of intestinal anastomoses-a histomorphological analysis.
AB  - BACKGROUND: It has been shown that crystalloid fluid-overload promotes
      anastomotic instability. As physiologic anastomotic healing requires the
      sequential infiltration of different cells, we hypothesized this to be altered by
      liberal fluid regimes and performed a histomorphological analysis. METHODS: 36
      Wistar rats were randomized into 4 groups (n=8-10 rats/group) and treated with
      either liberal (+) or restrictive (-) perioperative crystalline (Jonosteril =
      Cry) or colloidal fluid (Voluven = Col). Anastomotic samples were obtained on
      postoperative day 4, routinely stained and histophathologically reviewed.
      Anastomotic healing was assessed using a semiquantitative score, assessing
      inflammatory cells, anastomotic repair and collagenase activity. RESULTS:
      Overall, the crystalloid overload group (Cry (+)) showed the worst healing score
      (P < 0.01). A substantial increase of lymphocytes and macrophages was found in
      this group compared to the other three (P < 0.01). Both groups that received
      colloidal fluid (Col (+) and Col (-)) as well as the group that received
      restricted crystalloid fluid resuscitation (Cry (-)) had better intestinal
      healing. Collagenase activity was significantly higher in the Cry (+) group.
      CONCLUSION: Intraoperative infusion of high-volume crystalloid fluid leads to a
      pathological anastomotic inflammatory response with a marked infiltration of
      leukocytes and macrophages resulting in accelerated collagenolysis.

PMID- 23876363
TI  - Pancreatic resection: drain or no drain?
AB  - BACKGROUND: Despite reports of randomized, control trials and cohort studies that
      do not support the use of drains, most surgeons routinely place prophylactic,
      intraperitoneal drains at the time of pancreatic resections. We sought to
      evaluate the outcome of elective pancreatic resection with or without
      prophylactic peripancreatic drainage. The primary outcome was the rate of
      postoperative complications. Total pancreatectomy and pancreatectomy for chronic
      pancreatitis were excluded. METHODS: From September 2005 to February 2012, of the
      375 patients who had pancreatic surgery, 242 were eligible for the study. A drain
      was used in 130 and no drain was used in 112 patients. The data for the 2 groups
      were recorded in a prospective database. The statistical analysis compared
      variables using Chi-square and Fisher's exact tests for categorical variables and
      the independent-samples t-test for continuous variables. RESULTS: The
      demographic, operative, and pathologic data were similar between the 2 groups.
      There was no increase in the frequency or severity of the overall complications
      in the no drain group. In the drain and no drain groups, postoperative
      complications occurred in 64% and 67% of patients, respectively (P = .11); post
      pancreatectomy hemorrhage occurred in 19% and 23% (P = .33); and pancreatic
      fistula occurred in 16% and 13% (P = .34). The requirement for an interventional
      procedure was equivalent for both of the groups (14.6% and 20.5%; P = .15). The
      median hospital stay was 16 days (range, 2-98) and 18 (range, 7-131; P = .18),
      and the 90-day hospital mortality was 5.4% and 4.5% (P = .49) in the drain and
      the no drain groups, respectively. CONCLUSION: In a tertiary, high-volume,
      Hepatobiliary and pancreatic (HBP) surgery center, the routine prophylactic
      draining of the abdominal cavity after pancreatic resection did not decrease the
      frequency or severity of postoperative complications. Prophylactic peripancreatic
      drainage also did not decrease the requirement for interventional procedures.
      Interventional radiology and transgastric endoscopic drainage of the post
      pancreatectomy collection are feasible and improve patients' outcomes.
      Malnutrition and the type of operation were independent factors for postoperative
      complications.

PMID- 23876364
TI  - Impact of adjuvant external beam radiotherapy on survival in surgically resected
      gallbladder adenocarcinoma: a propensity score-matched Surveillance,
      Epidemiology, and End Results analysis.
AB  - BACKGROUND: We sought to define the utilization and effect of adjuvant external
      beam radiotherapy (XRT) on patients having undergone curative-intent resection
      for gallbladder cancer (GBC). METHODS: Using the Surveillance, Epidemiology, and
      End Results (SEER) database, we identified 5,011 patients with GBC who underwent
      resection between 1988 and 2009. The impact of XRT on survival was analyzed by
      the use of propensity-score matching by comparing clinicopathologic factors
      between patients who received resection only versus resection plus XRT. RESULTS:
      Median age was 72 years, and most patients were female (73.4%); 66.2% patients
      had intermediate to poorly differentiated tumors, and 19.1% had lymph node
      metastasis. The majority (75.0%) had "localized" disease by Surveillance,
      Epidemiology, and End Results classification. A total of 899 patients (17.9%)
      received XRT whereas 4,112 patients did not. Factors associated with receipt of
      XRT were younger age (odds ratio [OR] 5.33), tumor extension beyond the serosa
      (OR 1.55), intermediate- to poorly differentiated tumors (OR 1.56), and lymph
      node metastasis (OR 2.59) (all P < .05). Median and 1-year survival were 15
      months and 59.0%, respectively. On propensity-matched multivariate model, despite
      having more advanced tumors, XRT was independently associated with better long
      term survival at 1 year (hazard ratio 0.45; P < .001), but not 5 years (hazard
      ratio 1.06; P = .50). CONCLUSION: A total of 18% of patients with GBC received
      XRT after curative intent surgery. The use of adjuvant XRT was associated with a
      short-term survival benefit, but the benefit dissipated over time.

PMID- 23876365
TI  - The new global health.
AB  - Global health reflects the realities of globalization, including worldwide
      dissemination of infectious and noninfectious public health risks. Global health
      architecture is complex and better coordination is needed between multiple
      organizations. Three overlapping themes determine global health action and
      prioritization: development, security, and public health. These themes play out
      against a background of demographic change, socioeconomic development, and
      urbanization. Infectious diseases remain critical factors, but are no longer the
      major cause of global illness and death. Traditional indicators of public health,
      such as maternal and infant mortality rates no longer describe the health status
      of whole societies; this change highlights the need for investment in vital
      registration and disease-specific reporting. Noncommunicable diseases, injuries,
      and mental health will require greater attention from the world in the future.
      The new global health requires broader engagement by health organizations and all
      countries for the objectives of health equity, access, and coverage as priorities
      beyond the Millennium Development Goals are set. 

PMID- 23876366
TI  - Rapid and sensitive detection of shrimp infectious myonecrosis virus using a
      reverse transcription loop-mediated isothermal amplification and visual
      colorogenic nanogold hybridization probe assay.
AB  - This study reports a novel strategy for the detection of reverse transcription
      loop-mediated isothermal amplification (RT-LAMP) products derived from infectious
      myonecrosis virus (IMNV), causes a serious myonecrosis in Penaeus (Litopenaeus)
      vannamei, by using a ssDNA-labeled with gold nanoparticle (AuNP) probe. This
      technique relies on a self-aggregation method, when the AuNP aggregation is
      induced by an increasing of salt concentrations with visual detection. The
      presence of IMNV-LAMP target prevented an AuNP aggregation and a solution
      remained as pink color of AuNP, while non-complementary targets cannot prevent
      AuNP aggregation, resulting in a visible color change to purple color after
      addition of salt. By using the combination of LAMP and AuNP probe system, the
      total assay interval required approximately 50 min (exclude RNA preparation).
      Detection limit was 10 copies of IMNV RNA in vitro transcript that comparable to
      that of LAMP followed by LFD and nested RT-PCR, but it was 100-times more
      sensitive than RT-PCR methods. This assay can be adapted easily for rapid
      detection of other shrimp infectious diseases agents at low-cost with robust
      reagents and using a simple colorimetric detection method.

PMID- 23876367
TI  - Neuroprotective effects of madecassoside in early stage of Parkinson's disease
      induced by MPTP in rats.
AB  - In this study, we investigated the neuroprotective effects of madecassoside,
      isolated from the Chinese medicinal herb Centella asiatica, in the rat model of
      early phase of parkinsonism. During intragastric administrations of madecassoside
      for 7 days, the rats were injected with MPTP on the 7th day. And for the
      following 14 days, madecassoside were also administered. On the 14th day, the
      behavioral tests were assessed after 1h of administration. And then, the rats
      were sacrificed, substantia nigra and striatum were dissected. The content of DA,
      MDA, GSH, and Bcl-2/Bax gene expression levels and BDNF protein level was
      determined. Treatment with madecassoside was found to improve locomotor
      dysfunction and to protect dopaminergic neuron by antagonizing MPTP induced
      neurotoxicity. Madecassoside significantly attenuated the MPTP-induced reduction
      of dopamine in the striatum. The MDA contents were significantly decreased while
      the GSH levels, Bcl-2/Bax ratio and protein expression of BDNF were significantly
      increased in madecassoside treated groups. These results indicated that
      madecassoside was effective in recovering MPTP-induced early signs of
      parkinsonism via its neuroprotective effects including reversing the depletion of
      DA, antioxidant activity, increasing ratio of Bcl-2/Bax, increasing protein
      expression of BDNF.

PMID- 23876368
TI  - A new pentacyclic triterpene with potent antibacterial activity from Limnophila
      indica Linn. (Druce).
AB  - A new pentacyclic triterpenoid constituent, characterized as 3-oxo-olean
      12(13),18(19)-dien-29alpha-carboxylic acid (1) on the basis of detailed spectral
      studies, was isolated from the aerial parts and roots of Limnophila indica
      (Scrophulariaceae). Compound 1 exhibited considerable antibacterial activity
      against three Gram-positive bacteria viz. Bacillus subtilis, Staphylococcus
      aureus and Listeria monocytogenes (MICs within a range of 25-30 MUg/ml) and
      moderate activity against four Gram-negative bacteria Salmonella typhimurium,
      Escherichia coli, Pseudomonas aeruginosa, and Pantoea ananatis (MICs within a
      range of 30-100 MUg/ml). The plant pathogenic bacterium P. ananatis and human
      pathogenic S. typhimurium responded at comparatively higher concentrations of the
      compound 1, which were 75 and 100 MUg/ml respectively. The compound inhibited the
      growth of Gram-positive B. subtilis and Gram-negative P. aeruginosa completely
      with a clear bactericidal mode of action at their MIC values. The compound upon
      treatment on both B. subtilis and P. aeruginosa released substantial amount of
      nucleic acid in the external medium and also effected the change of morphology
      towards pleomorphicity, thereby indicating its probable action on cell membrane.
      Furthermore, the triterpenoid 1 was found not to inhibit a probiotic lactic acid
      bacterium Lactococcus lactis subsp. lactis LABW4 under in vitro condition and to
      possess no toxicity in Swiss albino mice.

PMID- 23876369
TI  - Synthesis, isolation, stereostructure and cytotoxicity of paclitaxel analogs from
      cephalomannine.
AB  - Four paclitaxel derivatives were afforded by preparative HPLC separation of two
      pairs of diastereoisomers, which were obtained by catalytic hydrogenation and
      epoxidation of the C-13 side-chain double bond of cephalomannine, a naturally
      occurring paclitaxel analog. The four paclitaxel derivatives were analyzed using
      NMR, CD spectroscopy, and side-chain hydrolysis in order to measure their optical
      rotations and GC characteristics. In this way, the stereoconfigurations of the
      products were determined. Evaluation of the compounds' activity indicated that
      they had differing cytotoxic activities: compound 5 had superior activity in BCG
      823 tumor cells compared to paclitaxel, while compound 7 had superior activity in
      HCT-8 and A549 tumor cells compared to paclitaxel. These results indicate that
      the stereoconfiguration of the paclitaxel N-acyl side chain has a significant
      impact on its activity. 

PMID- 23876370
TI  - Identification of diterpene alkaloids from Aconitum napellus subsp. firmum and
      GIRK channel activities of some Aconitum alkaloids.
AB  - Diterpene alkaloids neoline (1), napelline (2), isotalatizidine (3), karakoline
      (4), senbusine A (5), senbusine C (6), aconitine (7) and taurenine (8) were
      identified from Aconitum napellus L. subsp. firmum, four (2-4, 6) of which are
      reported for the first time from this plant. The structures were determined by
      means of LC-MS, 1D and 2D NMR spectroscopy, including (1)H-(1)H COSY, NOESY, HSQC
      and HMBC experiments. Electrophysiological effects of the isolated compounds,
      together with nine diterpene alkaloids previously obtained from Aconitum toxicum
      and Consolida orientalis were investigated on stable transfected HEK-hERG
      (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cell lines using automated patch
      clamp equipment. Significant blocking activity on GIRK channel was exerted by
      aconitine (7) (45% at 10 MUM), but no blocking activities of the other
      investigated compounds were detected. The tested compounds were inactive on hERG
      channel in the tested concentration. The comparison of the previously reported
      metabolites of A. napellus subsp. firmum and compounds identified in our
      experiment reveals substantial variability of the alkaloid profile of this taxon.

PMID- 23876371
TI  - [Medical knowledge in immunological security of red blood cells transfusion in
      Tunisia: evaluation of a CD-ROM of auto-learning].
AB  - In Tunisia, red blood cells (RBC) transfusion joins in a statutory frame but
      remains subject to failures because of the misunderstanding of legislation and
      regulations. Our purpose is to estimate the knowledge of the medical staff in the
      immunological safety of RBC transfusion before and after reading an auto
      education CD-ROM. It is a study of evaluation of an intervention. Eighty
      physicians participated to the study. The evaluation was done using an anonymous
      questionnaire, containing seven questions with multiple choices (QMC) relating to
      several items. The rate of good answers (RGA) calculated by questions and by
      items took into account the impact of the CD-ROM on the improvement of the
      answers after reading. The global average mark is 2.9/7. The RGA to questions
      varies from 22.5 % to 76.3%. All participants answered correctly to more than 50%
      of all items. Two answered correctly to all items. Among the participants, 31.3%
      answered to all "important" items, concerning ABO blood groups compatibility and
      ultimate bedside test. The rate of participation to the final evaluation was 83%.
      The impact of the CD-ROM was important and statistically significant. In the
      final evaluation, the global mark raised from 2.9 to 5.8/7, 31.5% (vs 2%)
      answered correctly all the questions and 95.5% (vs 31.3%) answered correctly all
      "important" items. This study revealed a misunderstanding of the doctors in
      immunological safety of RBC transfusions. Auto-teaching by CD-ROM was efficient.
      An improvement of the knowledge by continuous training is necessary in our
      country.

PMID- 23876372
TI  - [Blood products delivery by hospital blood banks in emergency situations in
      France].
AB  - In France, 13.5% of labile blood products (LBP) are delivered by 644 hospital
      blood banks, 472 being devoted to emergency only. A nation-wide survey aimed to
      describe their activity in emergency situations was carried out from September
      12th to 26th, 2011. All of 26 French regions but two participated, 548 (85%) of
      their hospital blood banks answered a questionnaire, of which 56% had actually
      issued blood in emergency situations. A total of 5241 LBP were delivered, 24% for
      utmost vital emergencies (UVE), 25% for vital emergencies (VE) and 51% for
      relative emergencies (RE). In UVE and VE, 47% of the packed red blood cells
      (PRBC) delivered were O RH1. Females were half of the 2102 patients, mean age was
      67 years. In UVE, banks devoted to emergency only, issued LBP for 228 patients
      (57%) and other banks for 169, acute digestive tract and surgical hemorrhage
      being the most frequent indications. The average number of PRBC transfused in 24
      hours per patient varied with the criticality of the emergency: 2.3 for RE, 3.9
      for VE and 6.1 for UVE. The mortality rate at 24 hours of first delivery was 1.2%
      in RE, 2.8% in VE and 10.1% in UVE. Time between prescription and start of
      transfusion of PRBC in UVE was within 15 minutes in 50% of cases and within 25
      minutes in 75% of cases for emergency devoted banks but respectively 25% and less
      than 50% for others. The proportion of surviving patients having received more
      than three LBP in 24 hours was 58% in UVE, 33% in VE and 10% in RE. The
      proportion of over the limit waiting time for PRBC transfusion in UVE is
      critical, mainly for banks not only devoted to emergencies. The high proportion
      of UVE and VE patients receiving three PRBC or less in 24 hours may also be an
      indicator that some physicians do not comply with emergency prescription rules.
      An effort should be made to improve the activity, in emergencies, of a part of
      hospital blood banks and the way physicians use them.

PMID- 23876373
TI  - Note on Friedman's 'what informatics is and isn't'.

PMID- 23876374
TI  - [Locoregional recurrence of Hurthle cell carcinoma].

PMID- 23876376
TI  - Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder.
AB  - Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) both are
      neuropsychiatric disorders associated with abnormalities in dopamine
      neurotransmission. Aims of this study were to quantify striatal D2/3 receptor
      availability in TS and OCD, and to examine dopamine release and symptom severity
      changes in both disorders following amphetamine challenge. Changes in
      [(11)C]raclopride binding potential (BP(ND)) were assessed using positron
      emission tomography before and after administration of d-amphetamine (0.3 mg kg(
      1)) in 12 TS patients without comorbid OCD, 12 OCD patients without comorbid
      tics, and 12 healthy controls. Main outcome measures were baseline striatal D2/3
      receptor BP(ND) and change in BP(ND) following amphetamine as a measure of
      dopamine release. Voxel-based analysis revealed significantly decreased baseline
      [(11)C]raclopride BP(ND) in bilateral putamen of both patient groups vs. healthy
      controls, differences being more pronounced in the TS than in the OCD group.
      Changes in BP(ND) following amphetamine were not significantly different between
      groups. Following amphetamine administration, tic severity increased in the TS
      group, which correlated with BP(ND) changes in right ventral striatum. Symptom
      severity in the OCD group did not change significantly following amphetamine
      challenge and was not associated with changes in BP(ND). This study provides
      evidence for decreased striatal D2/3 receptor availability in TS and OCD,
      presumably reflecting higher endogenous dopamine levels in both disorders. In
      addition, it provides the first direct evidence that ventral striatal dopamine
      release is related to the pathophysiology of tics.

PMID- 23876377
TI  - An analytical approach based on ESI-MS, LC-MS and PCA for the quali-quantitative
      analysis of cycloartane derivatives in Astragalus spp.
AB  - Astragalus species are widely used as health foods and dietary supplements, as
      well as drugs in traditional medicine. To rapidly evaluate metabolite
      similarities and differences among the EtOH extracts of the roots of eight
      commercial Astragalus spp., an approach based on direct analyses by ESI-MS
      followed by PCA of ESI-MS data, was carried out. Successively, quali-quantitative
      analyses of cycloartane derivatives in the eight Astragalus spp. by LC-ESI-MS(n)
      and PCA of LC-ESI-MS data were performed. This approach allowed to promptly
      highlighting metabolite similarities and differences among the various Astragalus
      spp. PCA results from LC-ESI-MS data of Astragalus samples were in reasonable
      agreement with both PCA results of ESI-MS data and quantitative results. This
      study affords an analytical method for the quali-quantitative determination of
      cycloartane derivatives in herbal preparations used as health and food
      supplements. 

PMID- 23876375
TI  - [The Spanish Association of Surgeon's audited teaching programme for rectal
      cancer. Results after six years].
AB  - BACKGROUND: The Spanish Rectal Cancer Project of the Spanish Association of
      Surgeons was established in 2006. The main objective of this observational study
      was to assess the results obtained by the hospitals trained in the period 2006
      2011, in order to evaluate whether this initiative has allowed acheivement of the
      observed quality standards in the Norwegian Rectal Cancer Project. METHODS:
      Between March 2006 and June 2012 a cohort of 10,006 patients treated during 2006
      2011 in 79 hospitals were included in the project registry. In 8.706 (94.5%)
      patients a rectal resection was performed. In 1.156 patients diagnosed with
      metastases or an R2-resection, the resection was considered palliative. The
      number of rectal resections with curative intent analyzed was 7.396 (80.3%). The
      outcome measures of the program effectiveness were local recurrence, metastases
      and survival. RESULTS: After a median follow-up period of 19.0 months
      (interquartile range [8.00-33.0]), local recurrence rate was 7.7 (9.1-6.2);
      metastases, 23.4 (25.6-21.1), and mortality 25.9 (28.1-23.7). CONCLUSION: This
      study shows that the oncological results achieved by the Spanish hospitals
      participating in the Rectal Cancer Project of the Spanish Association of Surgeons
      are similar to those observed in the Norwegian Colon and Rectal Cancer Project.

PMID- 23876378
TI  - The relationships among hemostatic markers, the withdrawal of fondaparinux due to
      a reduction in hemoglobin and deep vein thrombosis in Japanese patients
      undergoing major orthopedic surgery.
AB  - BACKGROUND: The relationships among the hemostatic markers, the development of
      deep vein thrombosis (DVT) and the withdrawal of fondaparinux due to a reduction
      in the hemoglobin levels were examined. METHODS: Two-hundred twenty-one Japanese
      patients who underwent major orthopedic surgery and were treated with 1.5mg of
      fondaparinux instead of 2.5mg of fondaparinux were studied. Forty-seven of 221
      patients discontinued fondaparinux treatment (withdrawal group) and 37 patients
      developed DVT. RESULTS: The age, frequency of total knee arthroplasty (TKA),
      withdrawal of fondaparinux, reduction of hemoglobin and the plasma levels of
      soluble fibrin (SF), D-dimer and fibrinogen and fibrin degradation product (FDP)
      on day 1 after the operation were significantly higher in the patients with DVT.
      Elevated SF, D-dimer or FDP levels were associated with the risk for DVT. The
      age, frequency of TKA or DVT, anti-Xa activity and the creatinine, FDP and D
      dimer levels were significantly higher in the withdrawal group. An anti-Xa level
      >0.33 mg/l and an elevated D-dimer or FDP level were associated with the risk of
      withdrawal. CONCLUSION: The age and SF levels, TKA and withdrawal of fondaparinux
      were related to the risk of DVT, and the anti-Xa activity, creatinine level and
      DVT were related to the risk of withdrawal of fondaparinux due to a reduction in
      hemoglobin.

PMID- 23876379
TI  - A novel splicing mutation in the SEDL gene causes spondyloepiphyseal dysplasia
      tarda in a large Chinese pedigree.
AB  - The X-linked form of spondyloepiphyseal dysplasia tarda (SEDT, OMIM# 313400) is a
      rare osteochondrodysplasia caused by mutations in the SEDL (TRAPPC2, OMIM#
      300202) gene. It is clinically characterized by disproportionate short stature,
      barrel-shaped chests and early development of degenerative joint disease. We
      report here a novel mutation in the intron 3 splice-donor site (c. 93+5G>C)
      segregated in an X-link pattern in a large Chinese family with SEDT. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis revealed that the
      mutation causes an aberrant splicing of exon 3, resulting in the elimination of
      31 codons in the exon and a considerable loss function of the SEDL protein. This
      mutation was not detected in the 100 healthy controls. This novel mutation adds
      to the spectrum of previously-identified disease-causing mutations. Pre
      symptomatic molecular diagnosis and prenatal diagnosis of the pregnant carriers
      could be helpful to families with SEDT. 

PMID- 23876381
TI  - Response to 'Use of an algorithm for identifying hidden drug-drug interactions in
      adverse event reports' by Gooden et al.

PMID- 23876380
TI  - VlincRNAs controlled by retroviral elements are a hallmark of pluripotency and
      cancer.
AB  - BACKGROUND: The function of the non-coding portion of the human genome remains
      one of the most important questions of our time. Its vast complexity is
      exemplified by the recent identification of an unusual and notable component of
      the transcriptome - very long intergenic non-coding RNAs, termed vlincRNAs.
      RESULTS: Here we identify 2,147 vlincRNAs covering 10 percent of our genome. We
      show they are present not only in cancerous cells, but also in primary cells and
      normal human tissues, and are controlled by canonical promoters. Furthermore,
      vlincRNA promoters frequently originate from within endogenous retroviral
      sequences. Strikingly, the number of vlincRNAs expressed from endogenous
      retroviral promoters strongly correlates with pluripotency or the degree of
      malignant transformation. These results suggest a previously unknown connection
      between the pluripotent state and cancer via retroviral repeat-driven expression
      of vlincRNAs. Finally, we show that vlincRNAs can be syntenically conserved in
      humans and mouse and their depletion using RNAi can cause apoptosis in cancerous
      cells. CONCLUSIONS: These intriguing observations suggest that vlincRNAs could
      create a framework that combines many existing short ESTs and lincRNAs into a
      landscape of very long transcripts functioning in the regulation of gene
      expression in the nucleus. Certain types of vlincRNAs participate at specific
      stages of normal development and, based on analysis of a limited set of cancerous
      and primary cell lines, they appear to be co-opted by cancer-associated
      transcriptional programs. This provides additional understanding of transcriptome
      regulation during the malignant state, and could lead to additional targets and
      options for its reversal.

PMID- 23876382
TI  - Primary and secondary human bocavirus 1 infections in a family, Finland.
AB  - Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for
      pneumonia and subsequently in his twin brother and other family members. The
      mother's nasopharyngeal samples intermittently showed HBoV1 DNA; the grandmother
      had HBoV1 reinfection. Findings in this family lead to consideration of HBoV
      virulence, latency, and reactivation. 

PMID- 23876384
TI  - Design, characterization, and in vitro cellular inhibition and uptake of
      optimized genistein-loaded NLC for the prevention of posterior capsular
      opacification using response surface methodology.
AB  - This study was to design an innovative nanostructured lipid carrier (NLC) for
      drug delivery of genistein applied after cataract surgery for the prevention of
      posterior capsular opacification. NLC loaded with genistein (GEN-NLC) was
      produced with Compritol 888 ATO, Gelucire 44/14 and Miglyol 812N, stabilized by
      Solutol((r)) HS15 by melt emulsification method. A 2(4) central composite design
      of 4 independent variables was performed for optimization. Effects of drug
      concentration, Gelucire 44/14 concentration in total solid lipid, liquid lipid
      concentration, and surfactant concentration on the mean particle size,
      polydispersity index, zeta potential and encapsulation efficiency were
      investigated. Analysis of variance (ANOVA) statistical test was used to assess
      the optimization. The optimized GEN-NLC showed a homogeneous particle size of
      90.16 nm (with PI=0.33) of negatively charged surface (-25.08 mv) and high
      encapsulation efficiency (91.14%). Particle morphology assessed by TEM revealed a
      spherical shape. DSC analyses confirmed that GEN was mostly entrapped in
      amorphous state. In vitro release experiments indicated a prolonged and
      controlled genistein release for 72 h. In vitro growth inhibition assay showed an
      effective growth inhibition of GEN-NLCs on human lens epithelial cells (HLECs).
      Preliminary cellular uptake test proved a enhanced penetration of genistein into
      HLECs when delivered in NLC.

PMID- 23876383
TI  - Ultrasound elastography in the head and neck. Part II. Accuracy for malignancy.
AB  - Ultrasound elastography (USE) describes a variety of ultrasound-based imaging
      techniques that measure tissue stiffness properties, and is currently under
      intense investigation for tissue characterization in several anatomic sites. This
      article summarizes the evidence regarding the accuracy of USE for malignancy in
      the head and neck. Currently, most published data pertains to small pilot studies
      with varied methodologies. Encouragingly, most studies have documented promising
      results for USE in terms of high accuracy for malignancy in thyroid nodules and
      cervical lymph nodes, which have surpassed conventional sonographic criteria.
      However, a minority of studies have documented opposite findings. USE seems to be
      suboptimal for salivary malignancies, and some evidence suggests that USE does
      not provide useful diagnostic information compared with conventional
      ultrasonography for miscellaneous neck masses. Further larger studies are
      required to validate these findings although, in view of the predominance of
      highly optimistic results for thyroid nodules and cervical lymph nodes, USE may
      become a useful ancillary technique in the routine diagnostic work-up of lesions
      in these tissues in the near future. 

PMID- 23876385
TI  - Molecular cloning and expression analysis of two beta-defensin genes in the blunt
      snout bream (Megalobrama amblycephala).
AB  - beta-Defensins are a group of cysteine-rich, cationic antimicrobial peptides that
      play important roles in innate immune system against pathogenic microbes
      invading. In this study, the part-length cDNA sequences of two beta-defensin
      genes (maBetaD-1, maBetaD-2) in blunt snout bream (Megalobrama amblycephala) were
      identified. Homology analysis showed that the cDNA sequences of maBetaD-1 and
      maBetaD-2 had high similarities to those in common carp and zebrafish. Real-time
      quantitative PCR results exhibited that expression level of maBetaD-1 in juvenile
      tissues was the highest in skin, followed by blood and liver, whereas maBetaD-2
      was lowly expressed in liver, kidney, brain and foregut. In the early development
      period, fertilized eggs to 31-day post-hatching (dph) larvae, the expression
      levels of maBetaD-1 were higher at the stage from heart beat stage to 3 dph with
      the highest value at 1 dph, whereas maBetaD-2 was expressed higher at fertilized
      eggs and late cleavage stages. Following bacterial stimulation in vivo by
      Aeromonas sobria, maBetaD-2 expressions were significantly up-regulated in liver,
      skin, gill, and foregut of juveniles, and maBetaD-1 expressions were
      significantly up-regulated in liver and skin. The results suggest that maBetaD-1
      and maBetaD-2 may play important roles in protecting blunt snout bream embryos,
      fry and juveniles from pathogenic microbe invading. 

PMID- 23876387
TI  - Acute hemorrhage related to a residual cervical pregnancy: management with
      curettage, tamponade, and cerclage.
AB  - Cervical ectopic pregnancy is uncommon, with no universally accepted protocol for
      conservative management of acute hemorrhage due to residual cervical ectopic
      pregnancy. Herein is presented the case of a 33-year-old woman with profuse
      vaginal bleeding 3 months after receiving treatment including intraamniotic
      potassium chloride injection, systemic methotrexate, and uterine artery
      embolization because of a cervical ectopic pregnancy. A residual cervical
      pregnancy was suspected. Hemorrhage was controlled using curettage, tamponade
      with a Bakri balloon, and cerclage. The balloon and cerclage were removed on
      postoperative day 2, with no recurrence of symptoms. Our experience suggests that
      a combination of curettage, balloon tamponade, and cerclage may be considered in
      the management of cervical ectopic pregnancies with acute hemorrhage, in
      particular in patients desiring future childbearing. 

PMID- 23876388
TI  - Perception of conversations: the importance of semantics and intonation in
      children's development.
AB  - In conversations, adults readily detect and anticipate the end of a speaker's
      turn. However, little is known about the development of this ability. We
      addressed two important aspects involved in the perception of conversational turn
      taking: semantic content and intonational form. The influence of semantics was
      investigated by testing prelinguistic and linguistic children. The influence of
      intonation was tested by presenting participants with videos of two dyadic
      conversations: one with normal intonation and one with flattened (removed)
      intonation. Children of four different age groups--two prelinguistic groups (6-
      and 12-month-olds) and two linguistic groups (24- and 36-month-olds)--and an
      adult group participated. Their eye movements were recorded, and the frequency of
      anticipated turns was analyzed. Our results show that (a) the anticipation of
      turns was reliable only in 3-year-olds and adults, with younger children shifting
      their gaze between speakers regardless of the turn taking, and (b) only 3-year
      olds anticipated turns better if intonation was normal. These results indicate
      that children anticipate turns in conversations in a manner comparable (but not
      identical) to adults only after they have developed a sophisticated understanding
      of language. In contrast to adults, 3-year-olds rely more strongly on prosodic
      information during the perception of conversational turn taking.

PMID- 23876386
TI  - Global and gene specific DNA methylation changes during zebrafish development.
AB  - DNA methylation is dynamic through the life of an organism. Previous studies have
      primarily focused on DNA methylation changes during very early embryogenesis. In
      this study, global and gene specific DNA methylation in zebrafish (Danio rerio)
      embryos, larvae and adult livers were compared. The percent methylation of
      cytosines was low in 2 to 4.3h post fertilization (hpf) zebrafish embryos and was
      consistently higher in zebrafish older than 6 hpf. Furthermore, quantitative real
      time PCR (qPCR) results showed relatively high DNA methyltransferase 1 (dnmt1)
      and low glycine N-methyltransferase (gnmt) mRNA expression in early
      embryogenesis. By studying methylation patterns and gene expression of five
      developmentally important genes, namely vasa, Ras-association domain family
      member 1 (rassf1), telomerase reverse transcriptase (tert), c-jun and c-myca, we
      found that the timing of changes in DNA methylation patterns was gene specific,
      and changes in gene expression were not necessarily correlated with the DNA
      methylation patterns. 

PMID- 23876390
TI  - Song performance and elaboration as potential indicators of male quality in Java
      sparrows.
AB  - Bird songs have evolved under sexual selection pressure. Songs include multiple
      features that are subject to female preference, but recent comparative research
      has indicated evolutionary tradeoffs between song performance and complexity in
      some species. Trill, a repetition of the same sound, is a performance-related
      song trait; higher trill performance can be achieved at the cost of song
      complexity at the among-species or population level. The aim of this study was to
      examine whether such tradeoffs also account for within-species variation in Java
      sparrow songs, which include both multiple trill types and non-trill parts. We
      found a great individual variation in trill proportion, trill performance, and
      song complexity. A positive association between trill performance and body size
      suggested that trills can serve as an indicator of male quality. However,
      contrary to the tradeoffs predicted by previous studies based on other passerine
      species, trill performance and song complexity, i.e., note repertoire, were
      positively correlated: males in better condition can sing songs with larger note
      repertoires and higher trill performance, which may explain how trills and non
      trill notes are both maintained and have co-evolved by sexual selection in Java
      sparrow songs. 

PMID- 23876389
TI  - Call to action for dengue vaccine failure.

PMID- 23876391
TI  - Valuing rewards to others in a prisoner's dilemma game.
AB  - People value rewards to others but discount those rewards based on social
      distance; rewards to a socially closer person are valued more than identical
      rewards to a socially more distant person (Jones and Rachlin, 2006). The concept
      of social discounting can explain cooperation and defection in two-player
      prisoner's dilemma (PD) games (Axelrod, 1980). The contingencies of a PD game are
      such that in any single game cooperation is costly to each player herself but
      beneficial to the other player. From the viewpoint of each player, the costs of
      cooperation are fully realized, but the benefits of cooperation are discounted by
      the social distance to the other player. The present experiment measured
      cooperation and defection in two PD-game conditions with differing reward
      magnitudes. In one (the 1-2-3-4 condition), the cost of cooperation exceeded its
      socially discounted benefit, and players were predicted to defect; in the other
      (the 1-2-9-10 condition), the discounted benefit of cooperation exceeded its
      cost, and players were predicted to cooperate. Over the course of repeated trials
      defection increased with the 1-2-3-4 condition but not with the 1-2-9-10
      condition. Moreover, participants who rated their partners as closer, relative to
      random classmates, cooperated at higher rates--consistent with social
      discounting.

PMID- 23876392
TI  - Soft calls and broadcast calls in the corncrake as adaptations to short and long
      range communication.
AB  - Because birds' acoustic signals function in antagonistic interactions between
      males and in female attraction, a majority of vocalisations are loud. In
      contrast, some birds, additionally produce soft vocalisations in escalated
      agonistic and sexual contexts. Nevertheless, the relationship between the
      acoustic parameters of such signals and their function is not clear. Here I
      investigate the sound transmission degradation properties of soft and broadcast
      (loud) calls in the corncrake using calls with natural and changed amplitude. I
      show that, if played at the same amplitude, the maximum limit for communication
      distance with soft calls was significantly shorter than that of broadcast calls,
      indicating that frequency structure is important in determining the range of both
      signals independently of their amplitude. At the same time, the values of excess
      attenuation were lower for soft calls than for broadcast calls at most distances,
      which suggests that the short transmission of soft calls is achieved mostly due
      to their low and narrow frequency ranges, promoting their masking by ambient
      noise. Finally, contrary to soft calls, changes in the energy of tails of echoes
      in broadcast calls were associated with the distance of propagation, which might
      be useful in assessing the distance to senders. I suggest that the acoustic
      structure of soft vocalisations can be used to limit the range of the signal,
      which might be helpful in eavesdropping avoidance, whereas broadcast calls are
      designed for long-range transmission. 

PMID- 23876393
TI  - Modulation of risk-taking behaviour in golden shiners (Notemigonus crysoleucas)
      using robotic fish.

PMID- 23876394
TI  - Editorial Commentary: rapid detection and investigation of an outbreak of
      Escherichia coli O157:H7 infections: shoe-leather epidemiology on and around the
      strawberry farm.

PMID- 23876395
TI  - High morbidity and mortality in adults hospitalized for respiratory syncytial
      virus infections.
AB  - BACKGROUND: Better understanding of complications and outcomes of adults
      hospitalized with respiratory syncytial virus (RSV) infection is necessary.
      METHODS: A retrospective cohort study was conducted on all adults (>= 18 years)
      admitted to 3 acute care general hospitals in Hong Kong with virologically
      confirmed RSV infection during 2009-2011 (N = 607). Adults hospitalized for
      seasonal influenza during the period were used for comparison (n = 547). Both
      infections were prospectively diagnosed following a standard protocol.
      Independent reviews of chest radiographs were performed by radiologists. Main
      outcome measures were all-cause death, respiratory failure requiring ventilatory
      support, and hospitalization duration. Cox proportional hazards models were used
      for analyses. RESULTS: The mean age of RSV patients was 75 (SD, 16) years; 87%
      had underlying conditions. Lower respiratory and cardiovascular complications
      were diagnosed in 71.9% (pneumonia, 42.3%; acute bronchitis, 21.9%; chronic
      obstructive pulmonary disease/asthma exacerbation, 27.3%) and 14.3% of patients,
      respectively; 12.5% had bacterial superinfections. Supplemental oxygen and
      ventilatory support were required in 67.9% and 11.1%, respectively. Crude all
      cause mortality was 9.1% and 11.9% within 30 days and 60 days, respectively; mean
      length of stay of survivors was 12 (SD, 13) days. Advanced age, radiographic
      pneumonia, requirement for ventilation, bacterial superinfection, and elevated
      urea level and white blood cell count were independently associated with poorer
      survival. Systemic corticosteroid use was associated with longer hospitalization
      and secondary infections. The overall outcomes of survival and length of stay
      were not significantly different from those in influenza. CONCLUSIONS: RSV can
      cause severe lower respiratory complications in older adults, resulting in
      respiratory failure, prolonged hospitalization, and high mortality similar to
      seasonal influenza. Corticosteroids did not seem to improve outcomes. The unmet
      need for antiviral therapy and vaccination against RSV in adults should be
      promptly addressed.

PMID- 23876396
TI  - Editorial commentary: respiratory syncytial virus: a global pathogen in an aging
      world.

PMID- 23876397
TI  - Escherichia coli O157:H7 infections associated with consumption of locally grown
      strawberries contaminated by deer.
AB  - BACKGROUND: An outbreak of Escherichia coli O157:H7 was identified in Oregon
      through an increase in Shiga toxin-producing E. coli cases with an
      indistinguishable, novel pulsed-field gel electrophoresis (PFGE) subtyping
      pattern. METHODS: We defined confirmed cases as persons from whom E. coli O157:H7
      with the outbreak PFGE pattern was cultured during July-August 2011, and
      presumptive cases as persons having a household relationship with a case testing
      positive for E. coli O157:H7 and coincident diarrheal illness. We conducted an
      investigation that included structured hypothesis-generating interviews, a
      matched case-control study, and environmental and traceback investigations.
      RESULTS: We identified 15 cases. Six cases were hospitalized, including 4 with
      hemolytic uremic syndrome (HUS). Two cases with HUS died. Illness was
      significantly associated with strawberry consumption from roadside stands or
      farmers' markets (matched odds ratio, 19.6; 95% confidence interval, 2.9
      infinity). A single farm was identified as the source of contaminated
      strawberries. Ten of 111 (9%) initial environmental samples from farm A were
      positive for E. coli O157:H7. All samples testing positive for E. coli O157:H7
      contained deer feces, and 5 tested farm fields had >= 1 sample positive with the
      outbreak PFGE pattern. CONCLUSIONS: The investigation identified fresh
      strawberries as a novel vehicle for E. coli O157:H7 infection, implicated deer
      feces as the source of contamination, and highlights problems concerning produce
      contamination by wildlife and regulatory exemptions for locally grown produce. A
      comprehensive hypothesis-generating questionnaire enabled rapid identification of
      the implicated product. Good agricultural practices are key barriers to wildlife
      fecal contamination of produce.

PMID- 23876398
TI  - Fasting insulin at baseline influences the number of cardiometabolic risk factors
      and R-R interval at 3years in a healthy population: the RISC Study.
AB  - AIM: This was a cross-sectional and longitudinal study of factors contributing to
      the number of cardiometabolic risk factors, common carotid artery intima-media
      thickness (CCA-IMT) and R-R interval in clinically healthy subjects without
      diabetes. METHODS: Anthropometric and cardiometabolic parameters were measured in
      the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC)
      Study cohort at baseline (n=1211) and 3years later (n=974). At baseline, insulin
      sensitivity was assessed by the euglycaemic clamp technique. The CCA-IMT was
      echographically measured and the R-R interval was electrocardiographically
      evaluated at baseline and at the 3-year follow-up. RESULTS: Higher baseline BMI,
      fasting insulin and tobacco use as well as greater changes in BMI and fasting
      insulin but lower adiponectin levels, were associated with a greater number of
      cardiometabolic risk factors at the 3-year follow-up independently of insulin
      sensitivity (all P<0.02). The CCA-IMT increased with the number of
      cardiometabolic risk factors (P=0.008), but was not related to fasting insulin,
      whereas higher fasting insulinaemia and its 3-year changes were significantly
      associated with a smaller R-R interval (P=0.005 and P=0.002, respectively). These
      relationships were independent of baseline age, gender, BMI, adiponectin, insulin
      sensitivity, tobacco use and physical activity. CONCLUSION: In clinically healthy
      subjects, fasting insulinaemia, adiponectin and lifestyle parameters are related
      to the presence of one or two cardiometabolic risk factors before criteria for
      the metabolic syndrome are met. These results underline the importance of fasting
      insulinaemia as an independent cardiometabolic risk factor at an early stage of
      disease development in a healthy general population.

PMID- 23876399
TI  - Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of cancer:
      a meta-analysis.
AB  - Studies investigating the impact of polymorphisms on monocyte chemotactic protein
      1 (MCP-1) and CC chemokine receptor 2 (CCR2) on the risk of cancer have reported
      inconsistent results. We performed a meta-analysis of 23 eligible studies to
      summarize the data describing the association between cancer risk and
      polymorphisms in MCP-1 A2518G and CCR2 V64I. Q-statistics and I(2) statistics
      were calculated to examine heterogeneity and summary odds ratios (ORs) and 95%
      confidence intervals (95% CI) were calculated using a random effects model.
      Potential sources of heterogeneity were investigated via subgroup and sensitivity
      analyses, and publication biases were estimated. Overall, MCP-1 and CCR2
      polymorphisms showed no significant associations with cancer risk (MCP-1-2518A/G,
      GG + GA vs. AA: OR=0.94, 95% CI=0.76-1.17; CCR2 V64I, AA+AG vs. GG: OR=1.27, 95%
      CI=0.87-1.86). However, strong evidence of heterogeneity was found among the
      investigated studies, and subgroup analyses were therefore conducted according to
      study location, cancer type, source of controls, and presence of deviation from
      the Hardy-Weinberg equilibrium (HWE). When the data were stratified by study
      location, the increased risk of cancer among A allele carriers of CCR2 V64I was
      observed only in studies conducted in Asian countries (AA+AG vs. GG: OR=1.65; 95%
      CI=1.25-2.18). This meta-analysis suggests that genetic polymorphisms of CCR2
      V64I may influence the susceptibility of cancer in Asian countries. Further well
      designed studies with larger sample sizes should be conducted.

PMID- 23876400
TI  - CCR1/CCL5 interaction promotes invasion of taxane-resistant PC3 prostate cancer
      cells by increasing secretion of MMPs 2/9 and by activating ERK and Rac
      signaling.
AB  - Castration-refractory prostate cancer (CRPC) is treated with taxane-based
      chemotherapy, but eventually becomes drug resistant. It is thus essential to
      identify novel therapeutic targets for taxane resistance in CRPC patients. We
      investigated the role of the chemokine (C-C motif) receptor 1 (CCR1) and its
      ligand, chemokine (C-C motif) ligand 5 (CCL5), in taxane-resistant CRPC using
      paclitaxel-resistant prostate cancer cells (PC3PR) established from PC3 cells. We
      found that the expression levels of CCR1 mRNA and protein were up-regulated in
      PC3PR cells compared to PC3 cells. In order to investigate the role of increased
      CCR1 in PC3PR cells, we stimulated cells with CCL5, one of the chemokine ligands
      of CCR1. In CCL5-stimulated PC3PR cells, siRNA-mediated knockdown of CCR1
      expression reduced phosphorylation of ERK1/2 and Rac1/cdc42. Furthermore, CCR1
      knockdown and MEK1/2 inhibition decreased CCL5-stimulated secretion of MMPs 2 and
      9, which play important roles in cancer cell invasion and metastasis. In the
      Matrigel invasion assay, knockdown of CCR1 and inhibition of the ERK and Rac
      signaling pathways significantly decreased the number of invading cells. Finally,
      the serum CCL5 protein level as measured by ELISA was not different among the
      three groups of patients: those with negative prostate biopsy, those at initial
      diagnosis of prostate cancer, and those with taxane-resistant prostate cancer.
      These results demonstrated for the first time that the interaction of CCR1 with
      CCL5 caused by increased expression of CCR1 promotes invasion of PC3PR cells by
      increasing secretion of MMPs 2 and 9 and by activating ERK and Rac signaling. Our
      findings suggest that CCR1 could be a novel therapeutic target for taxane
      resistant CRPC.

PMID- 23876401
TI  - GLiMMPS: robust statistical model for regulatory variation of alternative
      splicing using RNA-seq data.
AB  - To characterize the genetic variation of alternative splicing, we develop
      GLiMMPS, a robust statistical method for detecting splicing quantitative trait
      loci (sQTLs) from RNA-seq data. GLiMMPS takes into account the individual
      variation in sequencing coverage and the noise prevalent in RNA-seq data.
      Analyses of simulated and real RNA-seq datasets demonstrate that GLiMMPS
      outperforms competing statistical models. Quantitative RT-PCR tests of 26
      randomly selected GLiMMPS sQTLs yielded a validation rate of 100%. As population
      scale RNA-seq studies become increasingly affordable and popular, GLiMMPS
      provides a useful tool for elucidating the genetic variation of alternative
      splicing in humans and model organisms. 

PMID- 23876402
TI  - Biomarkers of acute kidney injury in pediatric cardiac surgery.
AB  - OBJECTIVES: Acute kidney injury (AKI) is a significant problem in children
      undergoing cardiopulmonary bypass (CPB). The aims of this study were to assess
      the diagnostic validity of serum CysC (sCysC), serum neutrophil gelatinase
      lipocalin (sNGAL), urine neutrophil gelatinase lipocalin (uNGAL), urine kidney
      injury molecule (uKIM)-1, and urine liver fatty acid-binding protein (uL-FABP) to
      predict AKI presence and severity in children undergoing CPB. DESIGN AND METHODS:
      We performed a prospective single-center evaluation of sCysC, sNGAL, uNGAL, uKIM
      1 and uL-FABP at 0, 2, 6, 24 and 48 h postoperatively in children undergoing CPB
      during cardiac surgery. AKI was defined as >=25% decrease in the estimated
      creatinine clearance (eCCl) from pre-operative baseline at 48h after surgery.
      RESULTS: Of the 112 patients, 18 patients (16.1%) developed AKI; four of them
      needed acute dialysis treatment and three AKI patients died. In the AKI compared
      to the non-AKI group, sCysC at 2h, and uNGAL and uL-FABP at 2-48 h were
      significantly increased, as well as CPB, aortic cross clamp time and length of
      hospital stay. Biomarkers increased with worsening AKI severity. At 2h after CPB
      the best accuracy for diagnosis of AKI had uL-FABP and sCysC with area under the
      receiver operator curve (AUC) of 0.89 and 0.73, respectively. At 6 and 24h after
      CPB the best AUC was found for uL-FABP (0.75 and 0.87 respectively) and for uNGAL
      (0.70 and 0.93, respectively). CONCLUSIONS: sCysC, uNGAL and uL-FABP are reliable
      early predictors for AKI after CPB. By allowing earlier timing of injury and
      earlier intervention, they could improve AKI outcome.

PMID- 23876403
TI  - Norovirus disease in the United States.
AB  - Although recognized as the leading cause of epidemic acute gastroenteritis across
      all age groups, norovirus has remained poorly characterized with respect to its
      endemic disease incidence. Use of different methods, including attributable
      proportion extrapolation, population-based surveillance, and indirect modeling,
      in several recent studies has considerably improved norovirus disease incidence
      estimates for the United States. Norovirus causes an average of 570-800 deaths,
      56,000-71,000 hospitalizations, 400,000 emergency department visits, 1.7-1.9
      million outpatient visits, and 19-21 million total illnesses per year. Persons
      >65 years of age are at greatest risk for norovirus-associated death, and
      children <5 years of age have the highest rates of norovirus-associated medical
      care visits. Endemic norovirus disease occurs year round but exhibits a
      pronounced winter peak and increases by <= 50% during years in which pandemic
      strains emerge. These findings support continued development and targeting of
      appropriate interventions, including vaccines, for norovirus disease.

PMID- 23876404
TI  - Quetiapine add-on therapy improves the depressive behaviors and hippocampal
      neurogenesis in fluoxetine treatment resistant depressive rats.
AB  - Quetiapine, an atypical antipsychotic, may have efficacy as augmentation therapy
      in treatment resistant depression (TRD), but evidence is limited and the
      underlying mechanism remains poorly understood. Therefore, this study was aimed
      to investigate whether and how quetiapine can be served as an augmentation agent
      in fluoxetine treatment resistant depressive rats induced by chronic
      unpredictable mild stress (CUMS). In this study, the effects of CUMS regimen and
      antidepressant treatment were assessed by behavioral tests and hippocampal
      neurogenesis. Approximately 20-30% of depressive rats respond poorly to
      fluoxetine treatment. In their hippocampus, a significant decrease of
      neurogenesis was also observed. However, quetiapine add-on therapy significantly
      improved the depressive behaviors and increased the number of the newborn neurons
      in the hippocampus of fluoxetine treatment resistant depressive rats. Thus, our
      results suggest that quetiapine may be used as an augmentation agent in the
      treatment resistant depression partly mediated by increasing the number of
      newborn neurons in the hippocampus. 

PMID- 23876405
TI  - Response to "Can 'humanized' mice improve drug development in the 21st century?".

PMID- 23876407
TI  - Universal approximation by radial basis function networks of Delsarte translates.
AB  - We prove that, under certain mild conditions on the kernel function (or
      activation function), the family of radial basis function neural networks
      obtained by replacing the usual translation with the Delsarte one, and taking the
      same smoothing factor in all kernel nodes, has the universal approximation
      property. 

PMID- 23876406
TI  - Protective role of antioxidants on thioacetamide-induced acute hepatic
      encephalopathy: biochemical and ultrastructural study.
AB  - Thioacetamide (TAA) has been used in development of animal models of acute
      hepatic encephalopathy (AHE). This experimental study was designed to evaluate
      effects of oral administration of vitamin C, vitamin E and their combination on
      liver and brain enzymes and their histologic and ultrastructure changes. Eighty
      Wistar rats were included and divided into five groups (16 each). Group 1
      (control) received saline once intraperitoneally (IP) then administered orally
      saline and corn oil for 3 days. Group 2 [hepatotoxic (TAA)] were received TAA
      (300mg/kg) once intraperitoneally (IP). Group 3 (vitamin C and TAA) received TAA
      (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin C
      (100mg/kg) daily for 3 days. Group 4 (vitamin E and TAA) received TAA (300mg/kg)
      once intraperitoneally (IP) and then administered orally vitamin E (200mg/kg)
      daily for 3 days. Group 5 (vitamin C and vitamin E and TAA) received TAA
      (300mg/kg) once intraperitoneally (IP) and then administered orally vitamin C
      (100mg/kg) in combination with vitamin E (200mg/kg) daily for 3 days. All rats
      were sacrificed 24h after last treatment under anesthesia. Blood samples were
      collected and serum was obtained for analysis of aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), total
      protein, triglyceride, cholesterol using spectrophotometer and ELISA kits. Liver
      and brain were extracted and tissue homogenate was used to measure
      malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO).
      Histological and ultrastructure examination were done. TAA induced significant
      increase of MDA and decreased in GSH and NO in both liver and brain homogenate
      with more liver affection, and increased in serum levels of AST, ALT,
      triglyceride, cholesterol and decreased in total protein. Furthermore, there is
      decrease in serum levels of AST, ALT, triglyceride, cholesterol and tissue levels
      of MDA and elevated serum total protein and tissue GSH and NO under the umbrella
      of vitamin C and vitamin E and their combination, although vitamin E is more
      efficient. These data showed protective effect of vitamins C and E, especially
      vitamin E against oxidative stress and hepatic and brain damage, and histological
      architecture of the liver in rats' model of acute hepatic encephalopathy elicited
      by TAA. 

PMID- 23876408
TI  - Perfusion imaging in brain disease.
AB  - Perfusion CT or MRI have been extensively developed over the last years and are
      accessible on most imaging machines. Perfusion CT has taken a major place in the
      assessment of a stroke. Its role has to be specified for the diagnosis and
      treatment of the vasospasm, complicating a subarachnoid hemorrhage. Perfusion MRI
      should be included in the assessment of any brain tumor, both at the time of the
      diagnosis as well as in the post-treatment monitoring. It is included in the
      multimodal approach required for the optimum treatment of this disease. The
      applications in epilepsy and the neurodegenerative diseases are in the evaluation
      process. 

PMID- 23876409
TI  - From personalized to public health genomics.

PMID- 23876410
TI  - Radiological and histopathological features of hepatic inflammatory
      myofibroblastic tumour: analysis of 10 cases.
AB  - AIM: To evaluate the radiological and histopathological features of hepatic
      inflammatory myofibroblastic tumours (IMTs), and improve the understanding of
      this tumour. MATERIALS AND METHODS: A retrospective analysis of radiological and
      histopathological features of 10 cases of IMT was carried out from May 2003 to
      September 2011 at the Second Xiangya Hospital of Central South University.
      RESULTS: Ten cases (five male and five female patients; age range 4-68 years)
      were enrolled. Computed tomography (CT) and magnetic resonance imaging (MRI)
      revealed that the lesions were regular, hypodense or hypointense (T1WI) masses
      with well-defined borders (n = 8) or ill-defined borders (n = 2). The maximum
      diameter ranged from 3.1-13.4 cm (mean = 6 cm). The masses showed homogeneous (n
      = 8) or inhomogeneous (n = 2) density. Contrast-enhanced CT and MRI showed the
      lesions were mildly, irregularly enhanced (n = 7) or not enhanced (n = 2) in the
      arterial phase and markedly enhanced in the portal venous phase or delayed phase.
      Hepatic arteriography revealed that the lesions were hypovascular and had a well
      defined border. One patient had lung metastasis with obvious arterial phase
      enhancement. None of the patients had a history of hepatitis, cirrhosis, or
      enlarged lymph nodes. Pathology showed that the gross appearance of the tumours
      was smooth. The tumour cells comprised spindle-shaped fibroblast and
      myofibroblast cells with abundant inflammatory cells. Immunohistochemistry showed
      that most were positive for vimentin, smooth muscle actin (SMA), and CD68, but
      negative for CD34, anaplastic lymphoma kinase (ALK), S-100, and CD117.
      CONCLUSION: Radiological features of IMT have some characteristics of an
      intermediate-grade malignant tumour. However, imaging alone cannot be used to
      diagnose IMT. Therefore, histopathological examination is necessary for
      confirmation.

PMID- 23876411
TI  - Metabolic engineering of Escherichia coli to minimize byproduct formate and
      improving succinate productivity through increasing NADH availability by
      heterologous expression of NAD(+)-dependent formate dehydrogenase.
AB  - Succinic acid is a specialty chemical having numerous applications in industrial,
      pharmaceutical and food uses. One of the major challenges in the succinate
      fermentation process is eliminating the formation of byproducts. In this study,
      we describe eliminating byproduct formate and improving succinate productivity by
      reengineering a high succinate producing E. coli strain SBS550MG
      Cms243(pHL413Km). The NAD(+)-dependent formate dehydrogenase gene (fdh1) of
      Candida boidinii was coexpressed with Lactococcus lactis pyruvate carboxylase
      (pycA) under the control of Ptrc and PpycA promoters in plasmid pHL413KF1. The
      newly introduced fdh1 converts 1 mol of formate into 1 mol of NADH and CO2. The
      reengineered strain SBS550MG-Cms243(pHL413KF1) retains the reducing power of
      formate through an increase in NADH availability. In anaerobic shake flask
      fermentations, the parent strain SBS550MG-Cms243(pHL413Km) consumed 99.86 mM
      glucose and produced 172.38 mM succinate, 16.16 mM formate and 4.42 mM acetate.
      The FDH bearing strain, SBS550MG-Cms243(pHL413KF1) consumed 98.43 mM glucose and
      produced 171.80 mM succinate, 1mM formate and 5.78 mM acetate. Furthermore,
      external formate supplementation to SBS550MG(pHL413KF1) fermentations resulted in
      about 6% increase in succinate yields as compared to SBS550MG(pHL413Km). In an
      anaerobic fed-batch bioreactor process, the average glucose consumption rate,
      succinate productivity, and byproduct formate concentration of SBS550MG(pHL413Km)
      was 1.40 g/L/h, 1g/L/h, and 17 mM, respectively. Whereas, the average glucose
      consumption rate, succinate productivity and byproduct formate concentration of
      SBS550MG(pHL413KF1) was 2 g/L/h, 2 g/L/h, 0-3 mM respectively. A high cell
      density culture of SBS550MG(pHL413KF1) showed further improvement in succinate
      productivity with a higher glucose consumption rate. Reduced levels of byproduct
      formate in succinate fermentation broth would provide an opportunity for reducing
      the cost associated with downstream processing, purification, and waste disposal.

PMID- 23876412
TI  - Pathway engineering of Bacillus subtilis for microbial production of N
      acetylglucosamine.
AB  - Glucosamine (GlcN) and its acetylated derivative, N-acetylglucosamine (GlcNAc),
      are widely used in nutraceutical and pharmaceutical industries. Currently, GlcN
      and GlcNAc are mainly produced by hydrolysis from crab and shrimp shells, which
      can cause severe environmental pollution and carries the potential risk of
      allergic reactions. In this study, we attempted to achieve microbial production
      of GlcNAc by pathway engineering of Bacillus subtilis 168. Specifically, glmS
      (encoding GlcN-6-phosphate synthase) from B. subtilis 168 and GNA1 (encoding
      GlcNAc-6-phosphate N-acetyltransferase) from Saccharomyces cerevisiae S288C were
      firstly co-overexpressed in B. subtilis; the level of GlcNAc reached 240mg/L in
      shake flask culture. Next, nagP, encoding the GlcNAc-specific enzyme of
      phosphotransferase system, was deleted to block the importation of extracellular
      GlcNAC, thus improving GlcNAc production to 615mg/L in shake flask culture. Then,
      nagA (encoding GlcNAc-6-phosphate deacetylase), gamA (encoding GlcN-6-phosphate
      deaminase), and nagB (encoding GlcN-6-phosphate deaminase) were deleted to block
      the catabolism of intracellular GlcNAc, thereby further increasing the GlcNAc
      titer to 1.85g/L in shake flask culture. Finally, microbial production of GlcNAc
      by the engineered B. subtilis 168 was conducted in a 3-L fed-batch bioreactor,
      and the GlcNAc titer reached 5.19g/L, which was 2.8-fold of that in shake flask
      culture. This is the first report regarding the pathway engineering of B.
      subtilis for microbial production of GlcNAc, and provides a good starting point
      for further metabolic engineering to achieve the industrial production of GlcNAc
      by a generally regarded as safe strain. 

PMID- 23876413
TI  - Design, construction and characterisation of a synthetic promoter library for
      fine-tuned gene expression in actinomycetes.
AB  - We developed a synthetic promoter library for actinomycetes based on the -10 and 
      35 consensus sequences of the constitutive and widely used ermEp1 promoter. The
      sequences located upstream, in between and downstream of these consensus
      sequences were randomised using degenerate primers and cloned into an integrative
      plasmid upstream of the gusA reporter gene. Using this system, we created
      promoters with strengths ranging from 2% to 319% compared with ermEp1. The
      strongest synthetic promoter was used in a proof-of-principle approach to achieve
      the overexpression of a natural type III polyketide synthase. We observed high
      correlation between the number of gusA reporter gene RNA-Seq reads and the GusA
      reporter protein activity, indicating that GusA is indeed a transcription-level
      reporter system. 

PMID- 23876414
TI  - Activation of glyoxylate pathway without the activation of its related gene in
      succinate-producing engineered Escherichia coli.
AB  - For the first time, glyoxylate pathway in the biosynthesis of succinate was
      activated without the genetic manipulations of any gene related with glyoxylate
      pathway. Furthermore, the inactivation of succinate biosynthesis by-products
      genes encoding acetate kinase (ackA) and phosphotransacetylase (pta) was proven
      to be the key factor to activate glyoxylate pathway in the metabolically
      engineered Escherichia coli under anaerobic conditions. In order to enhance the
      succinate biosynthesis specifically, the genes (i.e., ldhA, ptsG, ackA-pta, focA
      pflB, adhE) that disrupt by-products biosynthesis pathways were combinatorially
      deleted, while the E. coli malate dehydrogenase (MDH) was overexpression. The
      highest succinate production of 150.78 mM was obtained with YJ003 (DeltaldhA,
      ptsG, ackA-pta), which were 5-folds higher than that obtained with wild type
      control strain DY329 (25.13 mM). For further understand the metabolic response as
      a result of several genetic manipulations, an anaerobic stoichiometric model that
      takes into account the glyoxylate pathway have successfully been implemented to
      estimate the intracellular fluxes in various recombinant E. coli. The fraction to
      the glyoxylate pathway from OAA in DY329 was 0 and 31% in YJ003, which indicated
      that even without the absence of the iclR mutation; the glyoxylate pathway was
      also activated by deleting the by-products biosynthetic genes, and to be
      responsible for the higher succinate yields. For further strengthen glyoxylate
      pathway, a two-stage fed-batch fermentation process was developed by using a 600
      g l(-1) glucose feed to achieve a cell growth rate of 0.07 h(-1) in aerobic
      fermentation, and using a 750 g l(-1) glucose feed to maintain the residual
      glucose concentration around 40 g l(-1) when its residual level decreased to
      10gl(-1) in anaerobic fermentation. The best mutant strain YJ003/pTrc99A-mdh
      produces final succinate concentration of 274 mM by fed-batch culture, which was
      10-folds higher than that obtained with wild type control strain DY329. This
      study discovered that glyoxylate pathway could be activated by deleting
      glyoxylate pathway irrelevant genes (i.e., genes encoding acetate and lactate)
      and consequently the succinate biosynthesis was effectively improved. This work
      provides useful information for the modification of metabolic pathway to improve
      succinate production.

PMID- 23876416
TI  - Human deaths and third-generation cephalosporin use in poultry, Europe.

PMID- 23876417
TI  - [Fetal taking in some particular circumstances].
AB  - Fetal takings still concern about 6 to 7% of the pregnancies. If, in the majority
      of the cases, the taking does not present difficulty for a trained operator,
      particular circumstances related to maternal context (anticoagulating treatment,
      vaginal bleeding, fever...) may make the taking become more difficult. From a
      questionnaire sent to the French multidisciplinary centers for prenatal diagnosis
      and a review of the literature, we establish guidelines for fetal taking in these
      circumstances.

PMID- 23876415
TI  - Rectal cancer staging: focus on the prognostic significance of the findings
      described by high-resolution magnetic resonance imaging.
AB  - High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable
      tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides
      anatomic information for surgical planning and allows patients to be stratified
      into different groups according to the risk of local and distant recurrence. One
      of the objectives of the MDT is the preoperative identification of high-risk
      patients who will benefit from neoadjuvant treatment. For this reason, the
      correct evaluation of the circumferential resection margin (CRM), the depth of
      tumor spread beyond the muscularis propria, extramural vascular invasion and
      nodal status is of the utmost importance. Low rectal tumors represent a special
      challenge for the MDT, because decisions seek a balance between oncologic safety,
      in the pursuit of free resection margins, and the patient's quality of life, in
      order to preserve sphincter function. At present, the exchange of information
      between the different specialties involved in dealing with patients with rectal
      cancer can rank the contribution of colleagues, auditing their work and
      incorporating knowledge that will lead to a better understanding of the
      pathology. Thus, beyond the anatomic description of the images, the radiologist's
      role in the MDT makes it necessary to know the prognostic value of the findings
      that we describe, in terms of recurrence and survival, because these findings
      affect decision making and, therefore, the patients' life. In this review, the
      usefulness of HR MRI in the initial staging of rectal cancer and in the
      evaluation of neoadjuvant treatment, with a focus on the prognostic value of the
      findings, is described as well as the contribution of HR MRI in assessing
      patients with suspected or confirmed recurrence of rectal cancer. 

PMID- 23876418
TI  - [2013 annual meeting of the International Society for the Study of Women's Sexual
      Heath (ISSWH)].

PMID- 23876419
TI  - [Single-port surgery and adnexal procedures: which indications in oncological
      surgery?].
AB  - OBJECTIVE: To show the interest of single trocar in order to perform uni- or
      bilateral salpingo-oophorectomies. PATIENTS AND METHODS: A descriptive study
      monocentric. RESULTS: A total of 79 unilateral or bilateral salpingo
      oophorectomies were performed by single-port laparoscopy between January 2010 and
      September 2012 at the Institut Paoli-Calmettes (Marseille). There are three
      surgical indications: diagnostic, therapeutic and prophylactic. The median age
      was 50 years (22-78 years). The median BMI was 22.4 kg/m(2) (17.5 to 37.7
      kg/m(2)). The median blood loss was 0cc (0cc-50cc). The median hospital stay of
      patient was one day (0-6 days). The conversion rate in this study was 8.8%.
      DISCUSSION AND CONCLUSION: The single-port laparoscopic approach to perform uni-
      or bilateral salpingo-oophorectomies is a natural evolution of the conventional
      laparoscopy. If the cosmetic role seems obvious, its therapeutic value compared
      to traditional technique must be demonstrated by prospective studies with larger
      numbers.

PMID- 23876420
TI  - [What use of progesterone to prevent preterm birth?].
AB  - Widely prescribed in the years 1970-1980 to prolong gestation, progesterone has
      regained interest after the publication of randomized trials since 10 years. In
      women at increased risk of preterm birth with a history of preterm delivery or
      late miscarriage, the use of progesterone, especially intramuscularly may reduce
      the incidence of spontaneous preterm birth. In contrast, in cases of preterm
      labor or twin pregnancies, progesterone efficacy to reduce preterm birth has not
      been demonstrated. In women with asymptomatic midtrimester sonographic short
      cervix, randomized studies show conflicting results and new studies are necessary
      before its widespread utilisation.

PMID- 23876421
TI  - [Endometrioma and assisted reproductive technologies (ART): trends].

PMID- 23876423
TI  - Challenges of understanding brain function by selective modulation of neuronal
      subpopulations.
AB  - Neuronal networks confront researchers with an overwhelming complexity of
      interactions between their elements. A common approach to understanding neuronal
      processing is to reduce complexity by defining subunits and infer their
      functional role by selectively modulating them. However, this seemingly
      straightforward approach may lead to confusing results if the network exhibits
      parallel pathways leading to recurrent connectivity. We demonstrate limits of the
      selective modulation approach and argue that, even though highly successful in
      some instances, the approach fails in networks with complex connectivity. We
      argue to refine experimental techniques by carefully considering the structural
      features of the neuronal networks involved. Such methods could dramatically
      increase the effectiveness of selective modulation and may lead to a mechanistic
      understanding of principles underlying brain function. 

PMID- 23876422
TI  - ACCF/ACR/AIUM/ASE/IAC/SCAI/SCVS/SIR/SVM/SVS/SVU 2013 appropriate use criteria for
      peripheral vascular ultrasound and physiological testing part II: testing for
      venous disease and evaluation of hemodialysis access: a report of the american
      college of cardiology foundation appropriate use criteria task force.

PMID- 23876424
TI  - Advances in the pharmacological treatment of Parkinson's disease: targeting
      neurotransmitter systems.
AB  - For several decades, the dopamine precursor levodopa has been the primary therapy
      for Parkinson's disease (PD). However, not all of the motor and non-motor
      features of PD can be attributed solely to dopaminergic dysfunction. Recent
      clinical and preclinical advances provide a basis for the identification of
      additional innovative therapeutic options to improve the management of the
      disease. Novel pharmacological strategies must be optimized for PD by: (i)
      targeting disturbances of the serotonergic, noradrenergic, glutamatergic,
      GABAergic, and cholinergic systems in addition to the dopaminergic system, and
      (ii) characterizing alterations in the levels of neurotransmitter receptors and
      transporters that are associated with the various manifestations of the disease. 

PMID- 23876425
TI  - Molecular nexopathies: a new paradigm of neurodegenerative disease.
AB  - Neural networks provide candidate substrates for the spread of proteinopathies
      causing neurodegeneration, and emerging data suggest that macroscopic signatures
      of network disintegration differentiate diseases. However, how do protein
      abnormalities produce network signatures? The answer may lie with 'molecular
      nexopathies': specific, coherent conjunctions of pathogenic protein and intrinsic
      network characteristics that define network signatures of neurodegenerative
      pathologies. Key features of the paradigm that we propose here include
      differential intrinsic network vulnerability to propagating protein
      abnormalities, in part reflecting developmental structural and functional
      factors; differential vulnerability of neural connection types (e.g., clustered
      versus distributed connections) to particular pathogenic proteins; and
      differential impact of molecular effects (e.g., toxic-gain-of-function versus
      loss-of-function) on gradients of network damage. The paradigm has implications
      for understanding and predicting neurodegenerative disease biology. 

PMID- 23876426
TI  - Blurring the boundaries: developmental and activity-dependent determinants of
      neural circuits.
AB  - The human brain comprises approximately 100 billion neurons that express a
      diverse, and often subtype-specific, set of neurotransmitters and voltage-gated
      ion channels. Given this enormous complexity, a fundamental question is how is
      this achieved? The acquisition of neurotransmitter phenotype was viewed as being
      set by developmental programs 'hard wired' into the genome. By contrast, the
      expression of neuron-specific ion channels was considered to be highly dynamic
      (i.e., 'soft wired') and shaped largely by activity-dependent mechanisms. Recent
      evidence blurs this distinction by showing that neurotransmitter phenotype can be
      altered by activity and that neuron type-specific ion channel expression can be
      set, and perhaps limited by, developmental programs. Better understanding of
      these early regulatory mechanisms may offer new avenues to avert the behavioral
      changes that are characteristic of many mental illnesses. 

PMID- 23876427
TI  - The distribution of Dishevelled in convergently extending mesoderm.
AB  - Convergent extension (CE) is a conserved morphogenetic movement that drives axial
      lengthening of the primary body axis and depends on the planar cell polarity
      (PCP) pathway. In Drosophila epithelia, a polarised subcellular accumulation of
      PCP core components, such as Dishevelled (Dvl) protein, is associated with PCP
      function. Dvl has long been thought to accumulate in the mediolateral protrusions
      in Xenopus chordamesoderm cells undergoing CE. Here we present a quantitative
      analysis of Dvl intracellular localisation in Xenopus chordamesoderm cells. We
      find that, surprisingly, accumulations previously observed at mediolateral
      protrusions of chordamesodermal cells are not protrusion-specific but reflect
      yolk-free cytoplasm and are quantitatively matched by the distribution of the
      cytoplasm-filling lineage marker dextran. However, separating cell cortex
      associated from bulk Dvl signal reveals a statistical enrichment of Dvl in
      notochord-somite boundary-(NSB)-directed protrusions, which is dependent upon NSB
      proximity. Dvl puncta were also observed, but only upon elevated overexpression.
      These puncta showed no statistically significant spatial bias, in contrast to the
      strongly posteriorly-enriched GFP-Dvl puncta previously reported in zebrafish. We
      propose that Dvl distribution is more subtle and dynamic than previously
      appreciated and that in vertebrate mesoderm it reflects processes other than
      protrusion as such. 

PMID- 23876429
TI  - Lack of association between IL17A and IL17F polymorphisms and related serum
      levels in north Indians with tuberculosis.

PMID- 23876428
TI  - Distinct enhancers of ptf1a mediate specification and expansion of ventral
      pancreas in zebrafish.
AB  - Development of the pancreas and cerebellum require Pancreas-specific
      transcription factor-1a (Ptf1a), which encodes a subunit of the transcription
      factor complex PTF1. Ptf1a is required in succession for specification of the
      pancreas, proper allocation of pancreatic progenitors to endocrine and exocrine
      fates, and the production of digestive enzymes from the exocrine acini. In
      several neuronal structures, including the cerebellum, hindbrain, retina and
      spinal cord, Ptf1a is transiently expressed and promotes inhibitory neuron fates
      at the expense of excitatory fates. Transcription of Ptf1a in mouse is maintained
      in part by PTF1 acting on an upstream autoregulatory enhancer. However, the
      transcription factors and enhancers that initially activate Ptf1a expression in
      the pancreas and in certain structures of the nervous system have not yet been
      identified. Here we describe a zebrafish autoregulatory element, conserved among
      teleosts, with activity similar to that described in mouse. In addition, we
      performed a comprehensive survey of all non-coding sequences in a 67kb interval
      encompassing zebrafish ptf1a, and identified several neuronal enhancers, and an
      enhancer active in the ventral pancreas prior to activation of the autoregulatory
      enhancer. To test the requirement for autoregulatory control during pancreatic
      development, we restored ptf1a function through BAC transgenesis in ptf1a
      morphants, either with an intact BAC or one lacking the autoregulatory enhancer.
      We find that ptf1a autoregulation is required for development of the exocrine
      pancreas and full rescue of the ptf1a morphant phenotype. Similarly, we
      demonstrate that a ptf1a locus lacking the early enhancer region is also capable
      of rescue, but only supports formation of a hypoplastic exocrine pancreas.
      Through our dissection of the complex regulatory control of ptf1a, we identified
      separate cis-regulatory elements that underlie different aspects of its
      expression and function, and further demonstrated the requirement of maintained
      ptf1a expression for normal pancreatic morphogenesis. We also identified a novel
      enhancer that mediates initiation of ptf1a expression in the pancreas, through
      which the signals that specify the ventral pancreas are expected to exert their
      action. 

PMID- 23876430
TI  - "We have to what?": lessons learned about engaging support staff in an
      interprofessional intervention to implement MVA for management of spontaneous
      abortion.
AB  - BACKGROUND: Including support staff in practice change initiatives is a promising
      strategy to successfully implement new reproductive health services. The Resident
      Training Initiative in Miscarriage Management (RTI-MM) is an intervention
      designed to facilitate implementation of manual vacuum aspiration (MVA) for
      management of spontaneous abortion. The purpose of this study was to identify
      training program components that enhanced interprofessional training and provide
      lessons learned for engaging support staff in implementing uterine evacuation
      services. STUDY DESIGN: We conducted a secondary analysis of qualitative data to
      identify themes within three broad areas: interprofessional education, the role
      of support staff, and RTI-MM program components that facilitated support staff
      engagement in the process of implementing MVA services. RESULTS: We identified
      three key themes around interprofessional training and the role of support staff:
      "Training together is rare," "Support staff are crucial to practice change," and
      "Transparency, peers and champions." CONCLUSIONS: We present lessons learned that
      may be transferrable to other clinic sites: engage site leadership in a
      commitment to interprofessional training; engage support staff as teachers and
      learners and in shared values and building professionalism. IMPLICATIONS: This
      manuscript adds to what is known about how to employ interprofessional education
      and training to engage support staff in reproductive health services practice
      change initiatives. Lessons learned may provide guidance to clinical sites
      interested in interprofessional training, improving service delivery, or
      implementing new services.

PMID- 23876431
TI  - Rapid genotyping of three polymorphisms in the LBP gene using a triplex
      pyrosequencing approach.
AB  - We described a triplex polymerase chain reaction (PCR) and triplex pyrosequencing
      assay which allowed a simultaneous determination of three tag single nuleotide
      polymorphisms (tag SNPs) in the lipopolysaccharide-binding protein (LBP) gene:
      rs1780623, rs11536972 and rs2232618. This method enables a fast and cost
      effective genotyping and a simultaneous determination of the three tag SNPs. 

PMID- 23876432
TI  - Emergency department visit data for rapid detection and monitoring of norovirus
      activity, United States.
AB  - Noroviruses are the leading cause of gastroenteritis in the United States, but
      timely measures of disease are lacking. BioSense, a national-level electronic
      surveillance system, assigns data on chief complaints (patient symptoms)
      collected during emergency department (ED) visits to 78 subsyndromes in near real
      time. In a series of linear regression models, BioSense visits mapped by chief
      complaints of diarrhea and nausea/vomiting subsyndromes as a monthly proportion
      of all visits correlated strongly with reported norovirus outbreaks from 6 states
      during 2007-2010. Higher correlations were seen for diarrhea (R = 0.828-0.926)
      than for nausea/vomiting (R = 0.729-0.866) across multiple age groups. Diarrhea
      ED visit proportions exhibited winter seasonality attributable to norovirus;
      rotavirus contributed substantially for children <5 years of age. Diarrhea ED
      visit data estimated the onset, peak, and end of norovirus season within 4 weeks
      of observed dates and could be reliable, timely indicators of norovirus activity.

PMID- 23876433
TI  - The process of validation of a three-dimensional model for the identification of
      abuse in older adults.
AB  - Professional screening for abuse among older persons has been suggested as an
      efficient way to reach more individuals who are experiencing abuse, but effective
      screening depends on the use of succinct, structured and validated tools. The aim
      of the paper is to describe a process of constructing and validating a three
      dimensional screening tool for identification of abuse in older persons. It
      describes four studies that were conducted in the process of development and
      assessment of a three-dimensional screening tool for identification of abuse that
      consisted of direct questioning, identification of risk indicators and
      identification of signs of abuse. The study participants were, respectively, 108,
      730 and 1317 community-dwelling individuals, aged >=65, cognitively intact, and
      71 residents of long-term care facilities. Questionnaires included the three
      dimensional tool for identification of abuse, Expanded Indicators of Abuse (E
      IOA), list of signs of abuse, direct questioning for disclosure of abuse, and
      personal, medical and functioning details. Discriminant function analyses (DFA)
      and receiver-operating curve (ROC) analyses in each of the described steps showed
      good psychometric properties of the risk indicators. Regression analyses adjusted
      for socio-demographic and health variables showed that risk indicators
      significantly increased likelihood of abuse in individuals living in the
      community and in long-term care facilities. The three dimensions of
      identification of abuse were partially overlapped in their identification of
      different rates of abuse. In conclusion, the three-dimensional identification
      tool is efficient for identifying older adults experiencing abuse or at risk of
      abuse. 

PMID- 23876434
TI  - Plate-shaped non-contact ultrasonic transporter using flexural vibration.
AB  - We developed a plate-shaped non-contact transporter based on ultrasonic
      vibration, exploiting a phenomenon that a plate can be statically levitated at
      the place where its gravity and the acoustic radiation force are balanced. In the
      experiment, four piezoelectric zirconate titanate elements were attached to
      aluminum plates, on which lattice flexural vibration was excited at 22.3 kHz. The
      vibrating plates were connected to a loading plate via flexible posts that can
      minimize the influence of the flexure induced by heavy loads. The distribution of
      the vibration displacement on the plate was predicted through finite-element
      analysis to find the appropriate positions of the posts. The maximum levitation
      height of this transporter was 256 MUm with no load. When two vibrating plates
      were connected to a loading plate, the maximum transportable load was 4.0 kgf.

PMID- 23876435
TI  - Influence of preliminary ultrasonic treatment upon the steady-state creep of
      metals of different stacking fault energies.
AB  - This paper addresses the issue of the ultrasound effects upon the creep
      deformation of metals with different levels of stacking fault energy. The
      influence of preliminary ultrasound irradiation time upon the steady state creep
      rate is considered. Synthetic theory of irrecoverable deformation is taken as a
      mathematical apparatus. The analytical results show good agreement with
      experimental data. 

PMID- 23876436
TI  - The role of diet in triggering human inflammatory disorders in the modern age.
AB  - Previously uncommon human inflammatory disorders are emerging with alarming
      frequency, possibly triggered by environmental factors introduced through
      Westernization. This review highlights how Western diets heighten the
      inflammatory state promoting development of disease. Evidence that this can occur
      directly or indirectly through perturbations of host-microbe interactions are
      reviewed. 

PMID- 23876437
TI  - Genetic ACE I/D polymorphism and recurrence of atrial fibrillation after catheter
      ablation.
AB  - BACKGROUND: The angiotensin-converting enzyme (ACE) deletion allele, ACE D, is
      associated with increased cardiac ACE activity, cardiac fibrosis, and adverse
      outcomes in cardiovascular disease and has been linked with failure of antiatrial
      fibrillation (anti-AF) drug treatment. This study tested the hypothesis that the
      ACE gene insertion/deletion polymorphism associates with AF recurrence after
      catheter ablation. METHODS AND RESULTS: In 238 consecutive patients (69% male;
      mean age, 58+/-11 years) undergoing catheter ablation of paroxysmal (59%) or
      persistent (41%) AF, the ACE insertion/deletion polymorphism was genotyped using
      polymerase chain reaction. After a blanking period of 3 months, AF recurrence
      (defined as any atrial arrhythmia lasting >=30 s) was detected using serial 7-day
      Holter ECG recordings after 3, 6, and 12 months. AF recurrence was observed in
      39% and was associated with persistent AF, longer history of AF, previous
      antiarrhythmic drug use, previous use of diuretics, increased left atrial
      diameter, increased left ventricular end-diastolic diameter, additional linear
      ablation lesions, and ACE DD polymorphism. In multivariable analysis, left atrial
      diameter (odds ratio, 1.111; 95% confidence interval, 1.040-1.187; P=0.002) and
      ACE DD genotype (odds ratio, 2.251; 95% confidence interval, 1.056-4.798;
      P=0.036) remained predictors for AF recurrence. CONCLUSIONS: Left atrial
      enlargement and the ACE DD polymorphism are predictors for AF recurrence after
      catheter ablation. The association between the ACE DD polymorphism and AF
      recidivism supports the use of genetic data for predicting response to AF
      therapies and highlights the role of fibrosis in AF development.

PMID- 23876438
TI  - [Diagnostic value of a new procalcitonin cord sample-guided algorithm to manage
      newborns suspected of early-onset infection].
AB  - BACKGROUND: Diagnosis of early neonatal infection remains an emergency. Since
      clinical symptoms and biological markers are neither sensitive nor specific, many
      newborns suspected of infection undergo biological analysis and empirical
      antibiotic treatment while awaiting results. Recent studies underline the benefit
      of using procalcitonin (PCT) to differentiate inflammatory diseases and viral
      infections from bacterial infections. Joram shows that it is possible to go
      beyond the physiological peak of PCT in the first days of life by measuring PCT
      concentration in cord blood. The aim of this prospective study was to evaluate a
      new algorithm integrating the value of PCT in blood cord for taking care of
      newborns who have suspected infection. PATIENTS AND METHOD: The diagnostic value
      of the new algorithm was compared to the diagnostic value of the algorithm
      currently in use, by analyzing a 9-month prospective database of 1267 newborns
      suspected of infection. Infection status was established with the ANAES
      definition and clinical progression. RESULTS: Each infected newborn (n=8) would
      have been treated without delay with the current algorithm (based on ANAES
      guidelines) and this new algorithm. The new algorithm had the same diagnostic
      value as the current algorithm (P=0.5) with 87.5% sensitivity (95%CI [52-98])
      versus 100% (95%CI [87-100]) and 87.4% specificity (95%CI [85-90]) versus 83.8%
      (95%CI [81-86]). Fewer biological analyses 13.1% (95%CI [11-16]) versus 42.2%
      (95%CI [39-45]) were performed with the PCT cord-guided algorithm than with the
      current algorithm (P<0.05), leading to a 64.2% cost reduction. Antibiotics were
      significantly less used with the new algorithm: 13.1% (95%CI [11-16]) versus
      16.7% (95%CI [14-19]). CONCLUSION: PCT in cord blood could become a new and
      efficient marker to help neonatologists take care of newborns suspected of
      infection. These results must be confirmed by a larger multicenter prospective
      study.

PMID- 23876439
TI  - [An update on lactation physiology and breastfeeding].
AB  - Even though breastfeeding rates have increased in France, a sharp decline occurs
      rapidly in the first month. Lack of professional support is often held
      responsible, since many problems could be avoided if mothers were given adequate
      support. Continuing research into the physiology of breastfeeding shows a wide
      range of interindividual variations in anatomy, physiology, and normal
      breastfeeding patterns. An understanding of the physiology of lactation
      contributes to providing breastfeeding mothers with appropriate support and
      enabling them to have a successful breastfeeding experience. It allows health
      professionals to help mothers resolve their difficulties with an evidence-based
      guidance. 

PMID- 23876440
TI  - [Growth charts and intrauterine growth retardation].
AB  - Intrauterine growth restriction indicates that a fetus is unable to achieve its
      growth potential. The individual growth potential is approximated by
      customization of growth charts. Neonatal growth charts rely on body weight
      measures at birth while fetal growth charts rely on body weight estimated from
      biometric measurements of the fetus. The neonatal and fetal growth charts are not
      equivalent and have different meanings for epidemiologists and clinicians. Fetal
      growth charts also assess fetal growth velocity, but individual assessment of
      fetal weight may be flawed by lack of precision. Neonatal charts are constructed
      based on data obtained in the whole population or in a subgroup without
      gestational diseases. The two types of neonatal charts markedly differ at low
      gestational ages as 30% of preterm infants present intrauterine growth
      restriction, usually due to maternal diseases. Even if intrauterine growth
      restriction is a risk factor of fetal mortality, neonatal mortality, and short-
      and long-term morbidity, the predictive value of the charts (whether or not they
      are customized) at an individual level is low and may be improved by additional
      investigations. 

PMID- 23876441
TI  - [Gastric pneumatosis complicated by a neonatal digestive occlusion].
AB  - Gastric pneumatosis is a rare pathology. Its occurrence in the neonatal period
      requires looking for ulcerative-necrotizing enterocolitis in a context of
      prematurity or an underlying surgical obstacle. We report a case of gastric
      pneumatosis at a newborn child born at term, admitted on the third day of life
      for neonatal occlusion with a flat stomach. The abdomen without preparation
      showed substantial gastric distension with aspects of gastric pneumatosis and
      embellishes with images showing a double gastric bubble. The surgical exploration
      showed gastric pneumatosis, complete duodenal atresia located at the level of the
      second duodenal portion, and an annular pancreas. Progression was favorable after
      duodenostomy. 

PMID- 23876442
TI  - [Understand the neurodevelopment of language: a necessity to prevent learning
      disabilities in children].
AB  - Clinical and radiological knowledge of language development in the former
      premature infant compared to the newborn allows us to argue for exploration of
      the sensorimotor co-factors required for proper language development. There are
      early representations of the maternal language in the infant's visual, auditory,
      and sensorimotor areas, activated or stabilized by orofacial and articulatory
      movements. The functional architecture of language is different for vulnerable
      children such as premature infants. We have already mentioned the impact of early
      dysfunction of the facial praxis fine motor skills in this population presenting
      comprehension disorders. A recent meta-analysis confirms the increasing
      difficulty of understanding between 3 and 12 years, questioning the quality of
      the initial linguistic processes. A precise analysis of language, referenced from
      3 years of age, should be completed by sensorimotor tests to assess possible
      constraints in automating neurolinguistic foundations. The usual assessment at
      this age can exclude sensory disturbances and communication and offers guidance
      and socialization. However, a recent study shows the ineffectiveness of "language
      reinforced immersion" at 2 and 3 years in a population of vulnerable children.
      The LAMOPRESCO study of language and motor skills in the premature infant
      (National PHRC 2010) has assessed language and sensorimotor skills of preterm
      born (<33 weeks) 3.5-year-old children without cerebral palsy. Fragile children
      were randomized into 2 groups, 1 stimulated by a specific individual protocol,
      the other given guidance. The primary endpoint was phonology, assuming that it is
      composed of very early good-quality sensorimotor integration stabilized by the
      child's oral facial motor skills before 5 years of age. This developmental
      integrative dynamic validates the "motor theory of speech perception." Early and
      accurate assessment of language and the patient's constraints should
      differentiate and specify management strategies for all children, whatever their
      background and pathologies.

PMID- 23876443
TI  - [Maternal and neonatal factors associated with successful breastfeeding in very
      preterm infants].
AB  - OBJECTIVE: The main objective of this study was to evaluate the rate of
      breastfeeding at NICU discharge in a population of very preterm infants. The
      secondary objective was to identify maternal, gestational, and neonatal factors
      associated with successful breastfeeding at NICU discharge. MATERIALS AND
      METHODS: This is a retrospective descriptive study. All live births before 32
      weeks of gestational age (WGA) admitted to the NICU of the Amiens university
      hospital between 1 January 2009 and 30 June 2011 were included in the study,
      excluding infants who died during hospitalization or infants transferred to
      another hospital. Data on mothers and newborns were collected from the medical
      record. Statistical analysis was performed using the Chi(2) test for categorical
      variables and the Student t test for continuous variables. The significance
      threshold was set at P<0.05. RESULTS: Seventy-seven infants were included in the
      study. While 66% of the mothers wished to breastfeed at birth, the success rate
      of breastfeeding at hospital discharge was only 38%. The proportion of married
      women was significantly higher in the "successful breastfeeding" group (P=0.029).
      No significant difference was demonstrated regarding maternal age, maternal
      profession, proportion of non-smoking mothers, parity, type of pregnancy, type of
      delivery, duration of invasive ventilation and oxygen dependency, and surgery
      during hospitalization. CONCLUSION: The rate of breastfeeding of very preterm
      infants at hospital discharge is lower than the rates reported in the literature.
      The mother's marital status significantly influences the decision to breastfeed
      very preterm infants at discharge.

PMID- 23876444
TI  - Monitoring targeted therapy using dual-energy CT: semi-automatic RECIST plus
      supplementary functional information by quantifying iodine uptake of melanoma
      metastases.
AB  - AIM: Supplementary functional information can contribute to assess response in
      targeted therapies. The aim of this study was to evaluate semi-automatic RECIST
      plus iodine uptake (IU) determination in melanoma metastases under BRAF inhibitor
      (vemurafenib) therapy using dual-energy computed tomography (DECT). METHODS: Nine
      patients with stage IV melanoma treated with a BRAF inhibitor were included.
      Contrast-enhanced DECT was performed before and twice after treatment onset.
      Changes in tumor size were assessed according to RECIST. Quantification of IU
      (absolute value for total IU (mg) and volume-normalized IU (mg/ml)) was based on
      semi-automatic tumor volume segmentation. The decrease compared with baseline was
      calculated. RESULTS: The mean change of RECIST diameter sum per patient was -47%
      at the first follow-up (FU), -56% at the second FU (P < 0.01). The mean
      normalized IU per patient was -21% at the first FU (P < 0.2) and -45% at the
      second FU (P < 0.01). Total IU per patient, combining both normalized IU and
      volume, showed the most pronounced decrease: -89% at the first FU and -90% at the
      second FU (P < 0.01). CONCLUSION: Semi-automatic RECIST plus IU quantification in
      DECT enables objective, easy and fast parameterization of tumor size and contrast
      medium uptake, thus providing 2 complementary pieces of information for response
      monitoring applicable in daily routine.

PMID- 23876445
TI  - Selective encapsulation of hemoproteins from mammalian cells using mesoporous
      metal oxide nanoparticles.
AB  - A key requirement in successful protein encapsulation is the fabrication of
      selective protein supercaptors that are not impeded by the physical shape and
      three-dimensional hydrodynamics of the protein, exhibit minimal clogging effect
      but with high protein retention, and with uniformly sized adsorbent pores. We
      report a novel nanomagnet-selective supercaptor approach in the encapsulation of
      hemoprotein from mammalian cells using mesoporous metal oxide nanoparticles
      (NPs). Different morphologies of mesoporous NiO and Fe3O4 NPs were fabricated.
      Among these nanoadsorbents, NiO nanoroses (NRs) had higher loading capacity of
      hemoprotein than NiO nanospheres (NSs) and nanoplatelets (NPLs), or even
      superparamagnetic Fe3O4 NPs. The key finding of this study was that mesoporous
      NiO nanomagnet supercaptors show exceptional encapsulation and selective
      separation of high-concentration Hb from human blood. In this induced-fit
      separation model, in addition to the heme group distributions and protein-carrier
      binding energy, the morphology and magnetic properties of NiO NPs had a key
      function in broadening the controlled immobilization affinity and selectivity of
      hemoproteins. In addition, thermodynamics, kinetics, and theoretical studies were
      carried out to investigate the optimal performance of protein adsorption. 

PMID- 23876446
TI  - Structural changes to resorbable calcium phosphate bioceramic aged in vitro.
AB  - This work investigates the effect of mammalian cell culture conditions on 3D
      printed calcium phosphate scaffolds. The purpose of the studies presented was to
      characterise the changes in scaffold properties in physiologically relevant
      conditions. Differences in crystal morphologies were observed between foetal
      bovine serum-supplemented media and their unsupplemented analogues, but not for
      supplemented media containing tenocytes. Scaffold porosity was found to increase
      for all conditions studied, except for tenocyte-seeded scaffolds. The presence of
      tenocytes on the scaffold surface inhibited any increase in scaffold porosity in
      the presence of extracellular matrix secreted by the tenocytes. For acellular
      conditions the presence or absence of sera proteins strongly affected the rate of
      dissolution and the distribution of pore diameters within the scaffold. Exposure
      to high sera protein concentrations led to the development of significant numbers
      of sub-micron pores, which was otherwise not observed. The implication of these
      results for cell culture research employing calcium phosphate scaffolds is
      discussed. 

PMID- 23876447
TI  - Cell adhesion on zein films under shear stress field.
AB  - Vascular implants after implantation need to improve the ability of cells to
      withstand flow-shear stress. As such, we want to test whether zein films could
      improve the flow-shear stress resistance of cells by control of their surface
      morphology. We chose Collagen, poly L-lactic acid (PLLA) and three types of zein
      as the coating films and evaluated the flow-shear stress resistance of NIH3T3,
      and EA.hy926 on these respective films. The results showed that the retention of
      two cell lines on Collagen film was better than PLLA and zein films. The cell
      retention of EA.hy926 on Zein 3 film with higher roughness was better than Zein 1
      film with a flat surface in the first 2h. The cell retention of NIH3T3 on a
      rougher surface was always better than the smoother one under flow-shear stress
      condition for 6h. Observation of cell morphologies showed that the aspect ratio
      changed significantly for NIH3T3 cells upon flow-shear stress condition, as shown
      by reduced numbers of pseudopodia, increased cell rounding and shrinkage. Zein 3
      film with higher roughness improved the flow-shear stress resistance of cells and
      might be used in vascular implant coatings.

PMID- 23876448
TI  - Autochthonous human schistosomiasis, Malaysia.

PMID- 23876449
TI  - Machine learning approaches to diagnosis and laterality effects in semantic
      dementia discourse.
AB  - Advances in automatic text classification have been necessitated by the rapid
      increase in the availability of digital documents. Machine learning (ML)
      algorithms can 'learn' from data: for instance a ML system can be trained on a
      set of features derived from written texts belonging to known categories, and
      learn to distinguish between them. Such a trained system can then be used to
      classify unseen texts. In this paper, we explore the potential of the technique
      to classify transcribed speech samples along clinical dimensions, using
      vocabulary data alone. We report the accuracy with which two related ML
      algorithms [naive Bayes Gaussian (NBG) and naive Bayes multinomial (NBM)]
      categorized picture descriptions produced by: 32 semantic dementia (SD) patients
      versus 10 healthy, age-matched controls; and SD patients with left- (n = 21)
      versus right-predominant (n = 11) patterns of temporal lobe atrophy. We used
      information gain (IG) to identify the vocabulary features that were most
      informative to each of these two distinctions. In the SD versus control
      classification task, both algorithms achieved accuracies of greater than 90%. In
      the right- versus left-temporal lobe predominant classification, NBM achieved a
      high level of accuracy (88%), but this was achieved by both NBM and NBG when the
      features used in the training set were restricted to those with high values of
      IG. The most informative features for the patient versus control task were low
      frequency content words, generic terms and components of metanarrative
      statements. For the right versus left task the number of informative lexical
      features was too small to support any specific inferences. An enriched feature
      set, including values derived from Quantitative Production Analysis (QPA) may
      shed further light on this little understood distinction. 

PMID- 23876450
TI  - Weight gain among men and women who have a child enter their home.
AB  - Parenthood is associated with decreased physical activity and dietary changes.
      Previously, mothers have been the focus of studies examining the influence of
      children on parents' body mass index (BMI), largely ignoring whether parenting
      affects fathers. This study assessed weight gain in mothers and fathers (by birth
      or other), using longitudinal repeated-measures models to assess BMI changes over
      time; parents were compared with nonparents. Data were from the Coronary Artery
      Risk Development in Young Adults cohort study and included 2,881 black and white
      adults, ages 18 to 30 years, without children at baseline (1985-1986), and from
      four urban locations. At each time point (years 2, 5, and 7), changes in BMI from
      baseline were analyzed, comparing those who had their children in their household
      at that time point (parents) and those without children (nonparents). The "child
      effect" is the mean difference in BMI change in parents compared with nonparents.
      In fathers, overall, the child effect was not significant (black males: 0.30;
      P=0.09; white males: 0.03; P=0.77). Among black men, however, interactions
      between age and parental status were significant (P=0.02). Black men who were
      aged 18 to 24 years at baseline and became fathers during the next 7 years
      demonstrated a significant child effect, gaining an average of 0.68 more in BMI
      than nonfathers (P=0.003). Mothers of both races demonstrated the child effect;
      for blacks it was 0.65 (P=0.003) and for whites it was 1.12 (P<=0.001). These
      data reveal that becoming a parent can affect the BMI of some adults and suggest
      that obesity-prevention interventions for children and adult-focused healthy
      lifestyle interventions could have additional impact through a family focus
      targeting both parent and child outcomes.

PMID- 23876451
TI  - Differential mechanisms of opioidergic and dopaminergic systems of the ventral
      hippocampus (CA3) in anxiolytic-like behaviors induced by cholestasis in mice.
AB  - There are several studies carried out to test the effect of cholestasis on memory
      impairment and anxiolytic-like behaviors. Some previous studies have shown that
      cholestasis alters the activity of opioidergic and dopaminergic systems. The aim
      of the present study is however to investigate the role of mu opioid, D1 and D2
      dopamine ventral hippocampal (CA3) receptors upon cholestasis-induced anxiolytic
      like behaviors in hole-board task. Male mice weighing 25-30 g were used.
      Cholestasis was induced by ligation of the main bile duct. Our data indicated
      that cholestasis can induce anxiolytic-like response. Furthermore, the results
      showed that the intra-CA3 injection of naloxone, a mu receptor antagonist at 0.25
      and 0.5 ug/mouse, SCH23390, a D1 dopamine receptor antagonist or sulpiride, as a
      D2 dopamine receptor antagonist, 5 min before testing, reversed the cholestasis
      induced anxiolytic-like behaviors seven days after bile duct ligation (BDL).
      Unlike the higher dose of SCH23390 (0.5 ug/mouse) which induced anxiogenic-like
      behaviors, other doses of the above drugs did not alter the exploratory behaviors
      in examined mice. Based on our findings, co-administration of the subthreshold
      dose of naloxone (0.125 ug/mouse), SCH23390 or sulpiride, and SCH23390 with
      sulpiride, neither altered exploratory behaviors in animals nor reversed the
      cholestasis-induced anxiolytic-like behaviors, seven days post BDL. Current
      results demonstrated firstly, the anxiolytic-like behaviors are evident in
      cholestatic mice seven days post BDL; secondly, there are plausible mechanisms
      governing the involvement of the CA3 opioidergic and dopaminergic systems in this
      phenomenon and thirdly, there seem to be no interaction between these systems.

PMID- 23876452
TI  - Functional profile of the binary brain corticosteroid receptor system: mediating,
      multitasking, coordinating, integrating.
AB  - This contribution is focused on the action of the naturally occurring
      corticosteroids, cortisol and corticosterone, which are secreted from the
      adrenals in hourly pulses and after stress with the goal to maintain resilience
      and health. To achieve this goal the action of the corticosteroids displays an
      impressive diversity, because it is cell-specific and context-dependent in
      coordinating the individual's response to changing environments. These diverse
      actions of corticosterone are mediated by mineralocorticoid- and glucocorticoid
      receptors that operate as a binary system in concert with neurotransmitter and
      neuropeptide signals to activate and inhibit stress reactions, respectively.
      Classically MR and GR are gene transcription factors, but recently these
      receptors appear to mediate also rapid non-genomic actions on excitatory
      neurotransmission suggesting that they integrate functions over time. Hence the
      balance of receptor-mediated actions is crucial for homeostasis. This balanced
      function of mineralo- and glucocorticoid-receptors can be altered epigenetically
      by a history of traumatic (early) life events and the experience of repeated
      stressors as well as by predisposing genetic variants in signaling pathways of
      these receptors. One of these variants, mineralocorticoid receptor haplotype 2,
      is associated with dispositional optimism in appraisal of environmental
      challenges. Imbalance in receptor-mediated corticosterone actions was found to
      leave a genomic signature highlighting the role of master switches such as cAMP
      response element-binding protein and mammalian target of rapamycin to compromise
      health, and to promote vulnerability to disease. Diabetic encephalopathy is a
      pathology of imbalanced corticosterone action, which can be corrected in its pre
      stage by a brief treatment with the antiglucocorticoid mifepristone. 

PMID- 23876453
TI  - Mitochondrial DNA haplotype distribution patterns in Pinus ponderosa (Pinaceae):
      range-wide evolutionary history and implications for conservation.
AB  - PREMISE OF THE STUDY: Ponderosa pine (Pinus ponderosa Douglas ex P. Lawson & C.
      Lawson) exhibits complicated patterns of morphological and genetic variation
      across its range in western North America. This study aims to clarify P.
      ponderosa evolutionary history and phylogeography using a highly polymorphic
      mitochondrial DNA marker, with results offering insights into how geographical
      and climatological processes drove the modern evolutionary structure of tree
      species in the region. METHODS: We amplified the mtDNA nad1 second intron
      minisatellite region for 3,100 trees representing 104 populations, and sequenced
      all length variants. We estimated population-level haplotypic diversity and
      determined diversity partitioning among varieties, races and populations. After
      aligning sequences of minisatellite repeat motifs, we evaluated evolutionary
      relationships among haplotypes. KEY RESULTS: The geographical structuring of the
      10 haplotypes corresponded with division between Pacific and Rocky Mountain
      varieties. Pacific haplotypes clustered with high bootstrap support, and appear
      to have descended from Rocky Mountain haplotypes. A greater proportion of
      diversity was partitioned between Rocky Mountain races than between Pacific
      races. Areas of highest haplotypic diversity were the southern Sierra Nevada
      mountain range in California, northwestern California, and southern Nevada.
      CONCLUSIONS: Pinus ponderosa haplotype distribution patterns suggest a complex
      phylogeographic history not revealed by other genetic and morphological data, or
      by the sparse paleoecological record. The results appear consistent with long
      term divergence between the Pacific and Rocky Mountain varieties, along with more
      recent divergences not well-associated with race. Pleistocene refugia may have
      existed in areas of high haplotypic diversity, as well as the Great Basin,
      Southwestern United States/northern Mexico, and the High Plains.

PMID- 23876454
TI  - The desert moss Pterygoneurum lamellatum (Pottiaceae) exhibits an inducible
      ecological strategy of desiccation tolerance: effects of rate of drying on shoot
      damage and regeneration.
AB  - PREMISE OF THE STUDY: Bryophytes include clades that incorporate constitutive
      desiccation tolerance, especially terrestrial species. Here we test the
      hypothesis that the opposing ecological strategy of desiccation tolerance,
      inducibility, is present in a desert moss, and address this hypothesis by varying
      rates of drying in a laboratory study. Desiccation tolerance is arguably the most
      important evolutionary innovation relevant to the colonization of land by plants;
      increased understanding of the ecological drivers of this trait will eventually
      illuminate the responsible mechanisms and ultimately open doors to the potential
      for the application of this trait in cultivated plants. METHODS: Plants were
      cloned, grown in continuous culture (dehardened) for several months, and
      subjected to rates of drying (drying times) ranging from 30 min to 53 h,
      rehydrated and tested for recovery using chlorophyll fluorescence, leaf damage,
      and regeneration of protonema and shoots. KEY RESULTS: Rate of drying
      significantly affected all recovery responses, with very rapid drying rates
      severely damaging the entire shoot except the shoot apex and resulting in slower
      growth rates, fewer regenerative shoots produced, and a compromised
      photosynthetic system as inferred from fluorescence parameters. CONCLUSIONS: For
      the first time, a desert moss is shown to exhibit an ecological strategy of
      desiccation tolerance that is inducible, challenging the assumption that arid
      land bryophytes rely exclusively on constitutive protection. Results indicate
      that previous considerations defining a slow-dry event in bryophytes need
      reevaluation, and that the ecological strategy of inducible desiccation tolerance
      is probably more common than currently understood among terrestrial bryophytes.

PMID- 23876456
TI  - Aichi virus in sewage and surface water, the Netherlands.
AB  - Detection of Aichi virus in humans was initially reported in Japan in 1989. To
      establish a timeline for the prevalence of Aichi virus infection among humans in
      the Netherlands, we conducted molecular analysis of archival water samples from
      1987-2000 and 2009-2012. Aichi virus RNA was detected in 100% (8/8) of sewage
      samples and 100% (7/7) of surface water samples collected during 1987-2000 and
      100% (8/8) of sewage samples and 71% (5/7) of surface water samples collected
      during 2009-2012. Several genotype A and B Aichi virus lineages were observed
      over the 25-year period studied, but the time course of viral genetic diversity
      showed recent expansion of the genotype B population over genotype A. Our results
      show that Aichi virus has been circulating among the human population in the
      Netherlands since before its initial detection in humans was reported and that
      genotype B now predominates in this country. 

PMID- 23876457
TI  - Glycolytic control of vacuolar-type ATPase activity: a mechanism to regulate
      influenza viral infection.
AB  - As new influenza virus strains emerge, finding new mechanisms to control
      infection is imperative. In this study, we found that we could control influenza
      infection of mammalian cells by altering the level of glucose given to cells.
      Higher glucose concentrations induced a dose-specific increase in influenza
      infection. Linking influenza virus infection with glycolysis, we found that viral
      replication was significantly reduced after cells were treated with glycolytic
      inhibitors. Addition of extracellular ATP after glycolytic inhibition restored
      influenza infection. We also determined that higher levels of glucose promoted
      the assembly of the vacuolar-type ATPase within cells, and increased vacuolar
      type ATPase proton-transport activity. The increase of viral infection via high
      glucose levels could be reversed by inhibition of the proton pump, linking
      glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection.
      Taken together, we propose that altering glucose metabolism may be a potential
      new approach to inhibit influenza viral infection. 

PMID- 23876458
TI  - Analysis of boceprevir resistance associated amino acid variants (RAVs) in two
      phase 3 boceprevir clinical studies.
AB  - BACKGROUND: We investigated the frequency of RAVs among patients failing to
      achieve SVR in two clinical trials. We also investigated the impact of interferon
      responsiveness on RAVs and specific baseline RAVs relationship with boceprevir
      treatment failure. METHODS: Data are from 1020 patients enrolled into either
      SPRINT-2 or RESPOND-2; patients received a 4-week PR lead-in prior to receiving
      boceprevir or placebo. RAVs were analyzed via population-based sequence analysis
      of the NS3 protease gene (success rate of >90% at a virus level of >=
      10,000IU/mL) RESULTS: The high SVR rate in patients who received boceprevir
      resulted in a low rate of RAVs; 7% was detected at baseline in all patients,
      which rose to 15% after treatment. However, RAVs were detected in 53% of patients
      that failed to achieve SVR, which declined to 22.8% 6-14 months following
      cessation of boceprevir therapy. Baseline RAVs alone were not predictive of
      virologic outcome; poor interferon responsiveness was highly predictive of non
      SVR. RAVs were more frequently detected in poor interferon responders.
      CONCLUSIONS: We detected no association between the presence of baseline amino
      acid variants at boceprevir resistance-associated loci and outcome in the context
      of good IFN response.

PMID- 23876455
TI  - Affect regulation training (ART) for alcohol use disorders: development of a
      novel intervention for negative affect drinkers.
AB  - Although negative affect is a common precipitant of alcohol relapse, there are
      few interventions for alcohol dependence that specifically target negative
      affect. In this stage 1a/1b treatment development study, several affect
      regulation strategies (e.g., mindfulness, prolonged exposure, distress tolerance)
      were combined to create a new treatment supplement called affect regulation
      training (ART), which could be added to enhance cognitive-behavioral therapy
      (CBT) for alcohol dependence. A draft therapy manual was given to therapists and
      treatment experts before being administered to several patients who also provided
      input. After two rounds of manual development (stage 1a), a pilot randomized
      clinical trial (N=77) of alcohol-dependent outpatients who reported drinking
      often in negative affect situations was conducted (stage 1b). Participants
      received 12-weekly, 90-minute sessions of either CBT for alcohol dependence plus
      ART (CBT+ART) or CBT plus a healthy lifestyles control condition (CBT+HLS).
      Baseline, end-of-treatment, and 3- and 6-month posttreatment interviews were
      conducted. For both treatment conditions, participant ratings of treatment
      satisfaction were high, with CBT+ART rated significantly higher. Drinking outcome
      results indicated greater reductions in alcohol use for CBT+ART when compared to
      CBT+HLS, with moderate effect sizes for percent days abstinent, drinks per day,
      drinks per drinking day, and percent heavy drinking days. Overall, findings
      support further research on affect regulation interventions for negative affect
      drinkers. 

PMID- 23876459
TI  - The UL24 protein of herpes simplex virus 1 affects the sub-cellular distribution
      of viral glycoproteins involved in fusion.
AB  - Mutations in UL24 of herpes simplex virus type 1 can lead to a syncytial
      phenotype. We hypothesized that UL24 affects the sub-cellular distribution of
      viral glycoproteins involved in fusion. In non-immortalized human foreskin
      fibroblasts (HFFs) we detected viral glycoproteins B (gB), gD, gH and gL present
      in extended blotches throughout the cytoplasm with limited nuclear membrane
      staining; however, in HFFs infected with a UL24-deficient virus (UL24X), staining
      for the viral glycoproteins appeared as long, thin streaks running across the
      cell. Interestingly, there was a decrease in co-localized staining of gB and gD
      with F-actin at late times in UL24X-infected HFFs. Treatment with chemical agents
      that perturbed the actin cytoskeleton hindered the formation of UL24X-induced
      syncytia in these cells. These data support a model whereby the UL24 syncytial
      phenotype results from a mislocalization of viral glycoproteins late in
      infection. 

PMID- 23876460
TI  - Cadmium induces N-cadherin cleavage via ERK-mediated gamma-secretase activation
      in C6 astroglia cells.
AB  - N-cadherin has known to be involved in tumor progression and metastasis. However,
      it is still obscure about the signaling pathway involving in the processing of N
      cadherin. Thus, we examined which signaling pathway plays a major role in the
      processing of N-cadherin in C6 glioma cells following treatment of cadmium (Cd),
      a highly ubiquitous heavy metal. A cleavage product of N-cadherin, N-cad/CTF2 was
      observed by the treatment of Cd to C6 cells in a time and concentration-dependent
      manner. The production of N-cad/CTF2 was inhibited by pretreatment of gamma
      secretase inhibitors or siRNA transfection of nicastrin, indicating that gamma
      secretase is involved in the cleavage. Interestingly, Cd could activate both ERK
      and JNK signaling pathways in C6 cells; however, gamma-secretase-mediated N
      cad/CTF2 production by Cd was completely blocked by MEK1/2 inhibitors PD184352
      and U0126, but not by a JNK inhibitor SP600125, demonstrating that the ERK
      signaling pathway plays a major role in the cleavage. In addition, pretreatment
      of an antioxidant or Ca2+ blocker blocked the production of N-cad/CTF2 by Cd
      together with the inhibition of ERK1/2 phosphorylation. Collectively, these
      results suggest that Cd increases intracellular Ca2+ or ROS, which induces gamma
      secretase-dependent N-cad/CTF2 production via the activation of the ERK signaling
      pathway in C6 glial cells.

PMID- 23876461
TI  - Endothelial function acutely worse after drinking energy beverage.

PMID- 23876462
TI  - Relation of body mass index to bleeding events among patients with percutaneous
      coronary intervention: a meta-analysis.

PMID- 23876463
TI  - Peri-procedural tight glycemic control during early percutaneous coronary
      intervention up-regulates endothelial progenitor cell level and differentiation
      during acute ST-elevation myocardial infarction: effects on myocardial salvage.
AB  - BACKGROUND: We examined the effects of peri-procedural intensive glycemic control
      during early percutaneous coronary intervention (PCI) on the number and
      differentiation of endothelial progenitor cells (EPCs) and myocardial salvage
      (MS) in hyperglycemic patients with first ST-elevation myocardial infarction
      (STEMI). METHODS AND RESULTS: We conducted a randomized, prospective, open label
      study on 194 patients with STEMI undergoing PCI: 88 normoglycemic patients
      (glucose < 140 mg/dl) served as the control group. Hyperglycemic patients
      (glucose >=140 mg/dl) were randomized to intensive glycemic control (IGC) for
      almost 24 h after PCI (n = 54; 80-140 mg/dl) or conventional glycemic control
      (CGC, n = 52; 180-200 mg/dl). EPC number, differentiation, and SIRT1expression
      were assessed immediately before, 24 h, 7, 30 and 180 days after PCI. The primary
      end point of the study was salvage index, measured as the proportion of initial
      perfusion defect (acute technetium-99m sestamibi scintigraphy, performed 5 to 7
      days after STEMI) and myocardium salvaged by therapy (6 months after STEMI).
      Hyperglycemic patients had lower EPC number and differentiation and lower SIRT1
      levels than normoglycemic patients (P < 0.01). After the insulin infusion, mean
      plasma glucose during peri-procedural period was greater in CGC group than in IGC
      group (P < 0.001). The EPC number, their capability to differentiate, and SIRT1
      levels were significantly higher in IGC group than in CGC, peaking after 24 h (P
      < 0.01). In the IGC group, the salvage index was greater than in patients treated
      with CGC (P < 0.001). CONCLUSIONS: Optimal peri-procedural glycemic control, by
      increasing EPC number and their capability to differentiate, may improve the
      myocardial salvage.

PMID- 23876464
TI  - Electroanatomic mapping and catheter ablation of atrial tachycardia originating
      from the tricuspid annulus.

PMID- 23876465
TI  - Regional peak longitudinal-strain by 2D speckle-tracking TTE provides useful
      information to distinguish fibrotic from non-fibrotic lesions in LV myocardium on
      cardiac MR in hypertrophic cardiomyopathy.

PMID- 23876466
TI  - Joveini (Al-Akhawayni) and the early knowledge on circle of Willis.

PMID- 23876468
TI  - Reactive oxygen and nitrogen species in neurodegeneration.

PMID- 23876467
TI  - Rapid rule out of acute myocardial infarction using undetectable levels of high
      sensitivity cardiac troponin.
AB  - BACKGROUND: We examined whether undetectable levels of high-sensitivity cardiac
      Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with
      a single blood draw at presentation to the emergency department (ED). METHODS AND
      RESULTS: In a prospective multicenter study we used 4 different hs-cTn assays (hs
      cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in
      consecutive patients presenting with acute chest pain. The final diagnosis of AMI
      was adjudicated by two independent cardiologists using all available data
      including serial hs-cTnT levels. Mean follow up was 24 months. Among 2072
      consecutive patients with available hs-cTnT levels, 21% had an adjudicated
      diagnosis of AMI. Among AMI patients, 98.2% had initially detectable levels of hs
      cTnT (sensitivity 98.2%, 95%CI 96.3%-99.2%, negative predictive value (NPV)
      98.6%, 95%CI 97.0%-99.3%). Undetectable levels of hs-cTnT ruled out AMI in 26.5%
      of patients at presentation. The NPV was similar with the three hs-cTnI assays:
      among 1180 consecutive patients with available hs-cTnI (Siemens), the NPV was
      98.8%; among 1151 consecutive patients with available hs-cTnI (Beckman Coulter),
      the NPV was 99.2%; among 1567 consecutive patients with available hs-cTnI
      (Abbott), the NPV was 100.0%. The percentage of patients with undetectable levels
      of hs-cTnI was similar among the three hs-cTnI assays and ranged from 11.4% to
      13.9%. CONCLUSIONS: Undetectable levels of hs-cTn at presentation have a very
      high NPV and seem to allow the simple and rapid rule out of AMI. This criteria
      applies to much more patients with hs-TnT as compared to the investigated hs-cTnI
      assays.

PMID- 23876469
TI  - Transcription factor Nrf2 protects renal dopamine D1 receptor function during
      oxidative stress.
AB  - The renal dopaminergic system plays a significant role in controlling sodium
      excretion and blood pressure (BP). Overwhelming evidence shows that oxidative
      stress downregulates renal dopamine receptors (D1R), and antioxidant
      supplementation protects D1R function. However, the mechanisms for benefits of
      antioxidants in protecting D1R function are unknown. We investigated the role of
      nuclear factor E2-related factor 2 (Nrf2), a redox-sensitive transcription
      factor, in reducing oxidative stress, protecting renal D1R function and lowering
      BP in rats. Male Sprague-Dawley rats were treated with L-buthionine-sulfoximine
      (BSO) and sulforaphane for 4 weeks. Rats treated with BSO exhibited significant
      increase in oxidative stress and BP. BSO treatment reduced renal D1R expression
      and abolished SKF38393 (a D1R agonist)-induced Na/K-ATPase and Na/H-exchanger
      (NHE3) inhibition. Also, in these rats, SKF38393 failed to promote sodium
      excretion. BSO caused an increase in nuclear factor-kappaB expression, a modest
      nuclear translocation of Nrf2 and a moderate activation of phase II antioxidant
      enzymes. Treatment of rats with sulforaphane alone induced modest activation of
      Nrf2 and phase II antioxidant enzymes, although having no effect on BP, redox
      status, or D1R function. However, sulforaphane prevented oxidative stress,
      protected D1R function, and abrogated hypertension in BSO-treated rats. In these
      animals, sulforaphane, whereas attenuating nuclear factor-kappaB activation,
      caused a robust stimulation of Nrf2 and phase II antioxidant enzyme pathway. In
      conclusion, oxidative stress via nuclear factor-kappaB activation downregulated
      D1R function causing a decrease in sodium excretion, which contributed to an
      increase in BP. Sulforaphane via activation of Nrf2-phase II antioxidant enzyme
      pathway mitigated oxidative stress and nuclear factor-kappaB activation,
      preserved D1R function, and prevented hypertension. 

PMID- 23876470
TI  - Are observational studies more informative than randomized controlled trials in
      hypertension? Con side of the argument.

PMID- 23876471
TI  - Are observational studies more informative than randomized controlled trials in
      hypertension? Pro side of the argument.

PMID- 23876472
TI  - Is creatine kinase the intrinsic factor of smooth muscle enhancing vascular
      contractility in subjects of african ancestry?

PMID- 23876473
TI  - Maternal obesity: bad for baby's future.

PMID- 23876474
TI  - Complete renin-angiotensin-aldosterone system (RAAS) blockade in high-risk
      patients: recent insights from renin blockade studies.

PMID- 23876476
TI  - Maternal prepregnancy body mass index and their children's blood pressure and
      resting cardiac autonomic balance at age 5 to 6 years.
AB  - Adverse intrauterine conditions can program hypertension. Because one of the
      underlying mechanisms is thought to be cardiac autonomic balance, we investigated
      the association between prepregnancy body mass index (BMI) and blood pressure and
      indicators of the autonomic balance in the child at age 5 to 6 years. Also
      investigated was whether these associations were mediated by standardized birth
      weight and child BMI. Pregnant women (n=3074) participating in the Amsterdam Born
      Children and their Development study completed a questionnaire at gestational
      week 14. At age 5 to 6 years, offspring's sympathetic drive (pre-ejection
      period), parasympathetic drive (respiratory sinus arrhythmia), and heart rate
      were measured by electrocardiography and impedance cardiography at rest. Blood
      pressure was assessed simultaneously. After adjusting for possible
      maternal/offspring confounders, prepregnancy BMI was positively linearly
      associated with diastolic blood pressure (beta=0.11 mm Hg; 95% confidence
      interval, 0.05-0.17), systolic blood pressure (beta=0.14 mm Hg; 95% confidence
      interval, 0.07-0.21), but not with heart rate, sympathetic or parasympathetic
      drive. After adding birth weight and child BMI to the model, the independent
      effect size of prepregnancy body mass index on systolic blood pressure (beta=0.07
      mm Hg; 95% confidence interval, 0.00-0.14) and diastolic blood pressure
      (beta=0.07 mm Hg; 95% confidence interval, 0.01-0.13) decreased by ~50%. Birth
      weight did not mediate these relationships, but was independently and negatively
      associated with blood pressure. Child BMI was positively associated with blood
      pressure and partly mediated the association between prepregnancy BMI and blood
      pressure. In conclusion, higher prepregnancy BMI is associated with higher blood
      pressure in the child (aged 5-6 years) but does not seem to be attributable to
      early alterations in resting cardiac autonomic balance. Child BMI, but not birth
      weight, mediated the association between prepregnancy BMI and blood pressure. 

PMID- 23876475
TI  - Differential influence of distinct components of increased blood pressure on
      cardiovascular outcomes: from the atherosclerosis risk in communities study.
AB  - Elevation in blood pressure (BP) increases risk for all cardiovascular events.
      Nevertheless, the extent to which different indices of BP elevation may be
      associated to varying degrees with different cardiovascular outcomes remains
      unclear. We studied 13340 participants (aged 54 +/- 6 years, 56% women and 27%
      black) of the Atherosclerosis Risk in Communities Study who were free of baseline
      cardiovascular disease. We used Cox proportional hazards models to compare the
      relative contributions of systolic BP, diastolic BP, pulse pressure, and mean
      arterial pressure to risk for coronary heart disease, heart failure, stroke, and
      all-cause mortality. For each multivariable-adjusted model, the largest area
      under the receiver-operating curve (AUC) and smallest -2 log-likelihood values
      were used to identify BP measures with the greatest contribution to risk
      prediction for each outcome. A total of 2095 coronary heart disease events, 1669
      heart failure events, 771 stroke events, and 3016 deaths occurred during 18 +/- 5
      years of follow-up. In multivariable analyses adjusting for traditional
      cardiovascular risk factors, the BP measures with the greatest risk contributions
      were the following: systolic BP for coronary heart disease (AUC=0.74); pulse
      pressure for heart failure (AUC=0.79); systolic BP for stroke (AUC=0.74); and
      pulse pressure for all-cause mortality (AUC=0.74). With few exceptions, results
      were similar in analyses stratified by age, sex, and race. Our data indicate that
      distinct BP components contribute variably to risk for different cardiovascular
      outcomes.

PMID- 23876477
TI  - Biological production of monoethanolamine by engineered Pseudomonas putida S12.
AB  - Pseudomonas putida S12 was engineered for the production of monoethanolamine
      (MEA) from glucose via the decarboxylation of the central metabolite L-serine,
      which is catalyzed by the enzyme L-serine decarboxylase (SDC). The host was first
      evaluated for its tolerance towards MEA as well as its endogenous ability to
      degrade this alkanolamine. Growth inhibition was observed at MEA concentrations
      above 100 mM, but growth was never completely arrested even at 750 mM of MEA. P.
      putida S12 was able to catabolize MEA in the absence of ammonia, but deletion of
      the eutBC genes that encode ethanolamine ammonia-lyase (EAL) enzyme sufficed to
      eliminate this capacity. For the biological production of MEA, the sdc genes from
      Arabidopsis thaliana (full-length and a truncated version) and Volvox carteri
      were expressed in P. putida S12. From 20 mM of glucose, negligible amounts of MEA
      were produced by P. putida S12 DeltaeutBC expressing the sdc genes from A.
      thaliana and V. carteri. However, 0.07 mmol of MEA was obtained per g of cell dry
      weight of P. putida S12 DeltaeutBC expressing the truncated variant of the A.
      thaliana SDC. When the medium was supplemented with L-serine (30 mM), MEA
      production increased to 1.25 mmol MEA g-1 CDW, demonstrating that L-serine
      availability was limiting MEA production.

PMID- 23876479
TI  - Enhanced expression of codon optimized interferon gamma in CHO cells.
AB  - The human interferon-gamma (IFN-gamma) is a potential drug candidate for treating
      various diseases due to its immunomodulatory properties. The efficient production
      of this protein can be achieved through a popular industrial host, Chinese
      hamster ovary (CHO) cells. However, recombinant expression of foreign proteins is
      typically suboptimal possibly due to the usage of non-native codon patterns
      within the coding sequence. Therefore, we demonstrated the application of a
      recently developed codon optimization approach to design synthetic IFN-gamma
      coding sequences for enhanced heterologous expression in CHO cells. For codon
      optimization, earlier studies suggested to establish the target usage
      distribution pattern in terms of selected design parameters such as individual
      codon usage (ICU) and codon context (CC), mainly based on the host's highly
      expressed genes. However, our RNA-Seq based transcriptome profiling indicated
      that the ICU and CC distribution patterns of different gene expression classes in
      CHO cell are relatively similar, unlike other microbial expression hosts,
      Escherichia coli and Saccharomyces cerevisiae. This finding was further
      corroborated through the in vivo expression of various ICU and CC optimized IFN
      gamma in CHO cells. Interestingly, the CC-optimized genes exhibited at least 13
      fold increase in expression level compared to the wild-type IFN-gamma while a
      maximum of 10-fold increase was observed for the ICU-optimized genes. Although
      design criteria based on individual codons, such as ICU, have been widely used
      for gene optimization, our experimental results suggested that codon context is
      relatively more effective parameter for improving recombinant IFN-gamma
      expression in CHO cells. 

PMID- 23876478
TI  - Translatome analysis of CHO cells to identify key growth genes.
AB  - We report the first investigation of translational efficiency on a global scale,
      also known as translatome, of a Chinese hamster ovary (CHO) DG44 cell line
      producing monoclonal antibodies (mAb). The translatome data was generated via
      combined use of high resolution and streamlined polysome profiling technology and
      proprietary Nimblegen microarrays probing for more than 13K annotated CHO
      specific genes. The distribution of ribosome loading during the exponential
      growth phase revealed the translational activity corresponding to the maximal
      growth rate, thus allowing us to identify stably and highly translated genes
      encoding heterogeneous nuclear ribonucleoproteins (Hnrnpc and Hnrnpa2b1), protein
      regulator of cytokinesis 1 (Prc1), glucose-6-phosphate dehydrogenase (G6pdh),
      UTP6 small subunit processome (Utp6) and RuvB-like protein 1 (Ruvbl1) as
      potential key players for cellular growth. Moreover, correlation analysis between
      transcriptome and translatome data sets showed that transcript level and
      translation efficiency were uncoupled for 95% of investigated genes, suggesting
      the implication of translational control mechanisms such as the mTOR pathway.
      Thus, the current translatome analysis platform offers new insights into gene
      expression in CHO cell cultures by bridging the gap between transcriptome and
      proteome data, which will enable researchers of the bioprocessing field to
      prioritize in high-potential candidate genes and to devise optimal strategies for
      cell engineering toward improving culture performance. 

PMID- 23876480
TI  - Hydrophobic properties conferred to Kraft pulp by a laccase-catalysed treatment
      with lauryl gallate.
AB  - Hydrophobic properties were conferred to a high-lignin-content Kraft pulp by a
      laccase-catalysed treatment in the presence of lauryl gallate (LG). The treatment
      resulted in a two-fold increase in contact angle and conferred water absorption
      resistance to the pulp. Kappa number was increased, indicating that some phenolic
      compounds were incorporated in the pulp. A control treatment with LG alone did
      not affect water absorption, demonstrating that laccase was essential to attain
      these new properties. The loss of hydrophobicity after an acetone Soxhlet
      extraction highlighted that adsorbed acetone-soluble compounds played a key role
      in the properties. GC-FID and HPSEC-UV analysis of the acetone extract indicated
      the formation of dodecanol and different phenolic oligomers. SEM images showed
      the treatment-induced changes in the fibre network. Additional experiments with
      various reaction times and reactant concentrations highlighted the role of LG
      oxidation products in the introduction of absorption resistance. 

PMID- 23876481
TI  - The effect of alternating influent carbon source composition on activated sludge
      bioflocculation.
AB  - The impact of alternating influent carbon sources, i.e., glucose and starch, on
      activated sludge bioflocculation was investigated. To this end, four lab-scale
      reactors were operated during a long-term experiment. During this period the
      influent carbon source ratio (glucose/starch) was alternated every 7 or 35 days
      (i.e., a fast and slow switching frequency). Bioflocculation was monitored
      throughout the entire experiment using an extensive set of parameters, including
      macroscopic and microscopic activated sludge characteristics. Sludge
      hydrophobicity remained high (>80%) throughout the experiment indicating good
      bioflocculation. However, sludge settleability decreased for all four reactors
      after a 60 day adaptation period to the applied alternation in influent carbon
      source. During this adaptation period, floc size decreased due to the release of
      microcolonies. The subsequent period was characterized by a decrease in
      settleability, coinciding with a release of primary particles and an increase in
      floc size. The observed phenomena could be linked with the protein concentration
      near the floc surface. This fraction mainly consists of hydrolytic enzymes
      necessary for the degradation of starch and is responsible for a progressive
      deterioration of the EPS matrix. The results of this specific study indicate to
      be independent of the influent carbon source ratio or switching frequency.

PMID- 23876482
TI  - Mathematical model for aldol addition catalyzed by two D-fructose-6-phosphate
      aldolases variants overexpressed in E. coli.
AB  - Two D-fructose-6-phosphate aldolase variants namely, single variant FSA A129S and
      double variant FSA A129S/A165G, were used as catalysts in the aldol addition of
      dihydroxyacetone (DHA) to N-Cbz-3-aminopropanal. Mathematical model for reaction
      catalyzed by both enzymes, consisting of kinetic and mass balance equations, was
      developed. Kinetic parameters were estimated from the experimental data gathered
      by using the initial reaction rate method. The model was validated in the batch
      and continuously operated ultrafiltration membrane reactor (UFMR). The same type
      of kinetic model could be applied for both enzymes. The operational stability of
      the aldolases was assessed by measuring enzyme activity during the experiments.
      FSA A129S/A165G had better operational stability in the batch reactor (half-life
      time 26.7 h) in comparison to FSA A129S (half-life time 5.78 h). Both variants
      were unstable in the continuously operated UFMR in which half-life times were
      1.99 and 3.64 h for FSA A129S and FSA A129S/A165G, respectively.

PMID- 23876484
TI  - The rehabilitation of the multiple sclerosis patient.

PMID- 23876485
TI  - Orthotics and FES for maintenance of walking in patients with MS.

PMID- 23876486
TI  - Integrative therapies for multiple sclerosis.

PMID- 23876483
TI  - Type I interferon and lymphangiogenesis in the HSV-1 infected cornea - are they
      beneficial to the host?
AB  - Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that can
      result in significant human morbidity. Within the cornea, it was thought the
      initial recognition of the pathogen was through Toll-like receptors expressed
      on/in resident cells that then elicit pro-inflammatory cytokine production,
      activation of anti-viral pathways, and recruitment of leukocytes. However, our
      lab has uncovered a novel, TLR-independent innate sensor that supersedes TLR
      induction of anti-viral pathways following HSV-1 infection. In addition, we have
      also found HSV-1 induces the genesis of lymphatic vessels into the cornea proper
      by a mechanism independent of TLRs and unique in the field of neovascularization.
      This review will focus on these two innate immune events during acute HSV-1
      infection of the cornea. 

PMID- 23876487
TI  - Optimization of light use efficiency for biofuel production in algae.
AB  - A major challenge for next decades is development of competitive renewable energy
      sources, highly needed to compensate fossil fuels reserves and reduce greenhouse
      gas emissions. Among different possibilities, which are currently under
      investigation, there is the exploitation of unicellular algae for production of
      biofuels and biodiesel in particular. Some algae species have the ability of
      accumulating large amount of lipids within their cells which can be exploited as
      feedstock for the production of biodiesel. Strong research efforts are however
      still needed to fulfill this potential and optimize cultivation systems and
      biomass harvesting. Light provides the energy supporting algae growth and
      available radiation must be exploited with the highest possible efficiency to
      optimize productivity and make microalgae large scale cultivation energetically
      and economically sustainable. Investigation of the molecular bases influencing
      light use efficiency is thus seminal for the success of this biotechnology. In
      this work factors influencing light use efficiency in algal biomass production
      are reviewed, focusing on how algae genetic engineering and control of light
      environment within photobioreactors can improve the productivity of large scale
      cultivation systems. 

PMID- 23876488
TI  - What planar lipid membranes tell us about the pore-forming activity of
      cholesterol-dependent cytolysins.
AB  - Pore-forming toxins are an important group of natural molecules that damage
      cellular membranes by forming transmembrane pores. They are used by many
      organisms for attack or defense and similar proteins are employed in the immune
      system of vertebrates. Various biophysical approaches have been used to
      understand how these proteins act at the molecular level. One of the most useful,
      in terms of monitoring pore formation in real time, is a method that employs
      planar lipid membranes and involves ionic current measurements. Here we highlight
      the advantages and possibilities that this approach offers and show how it can
      advance understanding of the pore-forming mechanism and pore properties for one
      of the most important families of natural toxins, the cholesterol-dependent
      cytolysins. 

PMID- 23876489
TI  - Asian musk shrew as a reservoir of rat hepatitis E virus, China.

PMID- 23876490
TI  - Diagnostic accuracy of preoperative tests for lymph node status in endometrial
      cancer: a systematic review.
AB  - BACKGROUND: Approximately 72% of endometrial cancers are FIGO stage I at
      diagnosis and about 10% have lymph node metastases. An ideal diagnostic test for
      nodal disease would be able to prevent both overtreatment (i.e. unnecessary
      lymphadenectomy) and undertreatment (i.e. withholding lymphadenectomy or adjuvant
      postoperative treatment to patients with lymph node metastases). OBJECTIVES: In
      this review we compare the accuracy of preoperative tests (computed tomography,
      magnetic resonance imaging, positron emission tomography-computed tomography, CA
      125 serum levels, and ultrasonography) for the detection of lymph node metastases
      in endometrial cancers with the final histopathologic diagnosis after complete
      pelvic and para-aortic lymphadenectomy as the gold standard. METHOD: A systematic
      search in MEDLINE (using PubMed), Embase and The Cochrane Library was performed
      up to 23 July 2012. RESULTS: We found one article that met our inclusion criteria
      for computed tomography, none for magnetic resonance imaging, 2 for positron
      emission tomography/computed tomography), 2 for CA-125 and none for
      ultrasonography. CONCLUSIONS: Due to the lack of high-quality articles on a
      preoperative test for lymph node status in endometrial cancer, no proper
      comparison between these modalities can be made.

PMID- 23876491
TI  - A synthetic connexin 43 mimetic peptide augments corneal wound healing.
AB  - The ability to safely and quickly close wounds and lacerations is an area of need
      in regenerative medicine, with implications toward healing a wide range of
      tissues and wounds. Using an in vivo corneal injury model, our study applied a
      newly developed peptide capable of promotion of wound healing and epithelial
      regeneration. The alpha-carboxy terminus 1 (alphaCT1) peptide is a 25 amino acid
      peptide from the C-terminus of connexin 43 (Cx43), modified to promote cellular
      uptake. Previous studies applying alphaCT1 to excisional skin wounds in porcine
      models produced tissues having an overall reduced level of scar tissue and
      decreased healing time. Rapid metabolism of alphaCT1 in previous work led to the
      investigation of extended release on wound healing rate used in this study. Here
      we delivered alphaCT1 both directly, in a concentrated pluronic solution, and in
      a sustained system, using polymeric alginate-poly-l-ornithine (A-PLO)
      microcapsules. Cell toxicity analysis showed minimal cell-loss with microcapsule
      treatment. Measurement of wound healing using histology and fluorescence
      microscopy indicated significant reduction in healing time of alphaCT1
      microcapsule treated rat corneas compared with controls (88% vs. 38%). RT-PCR
      analysis showed an initial up regulation followed by down regulation of the gene
      keratin-19 (Krt19). Zonula occludens 1 (ZO-1) showed an opposite down regulation
      followed by an up regulation whereas Cx43 showed a biphasic response.
      Inflammatory indexes demonstrated a reduction in the inflammation of corneas
      treated with alphaCT1 microcapsules when compared with pluronic gel vehicle.
      These results suggest alphaCT1, when applied in a sustained release system, acts
      as a beneficial wound healing treatment. 

PMID- 23876492
TI  - Clinical and pharmacogenetic predictors of circulating atorvastatin and
      rosuvastatin concentrations in routine clinical care.
AB  - BACKGROUND: A barrier to statin therapy is myopathy associated with elevated
      systemic drug exposure. Our objective was to examine the association between
      clinical and pharmacogenetic variables and statin concentrations in patients.
      METHODS AND RESULTS: In total, 299 patients taking atorvastatin or rosuvastatin
      were prospectively recruited at an outpatient referral center. The contribution
      of clinical variables and transporter gene polymorphisms to statin concentration
      was assessed using multiple linear regression. We observed 45-fold variation in
      statin concentration among patients taking the same dose. After adjustment for
      sex, age, body mass index, ethnicity, dose, and time from last dose, SLCO1B1
      c.521T>C (P<0.001) and ABCG2 c.421C>A (P<0.01) were important to rosuvastatin
      concentration (adjusted R(2)=0.56 for the final model). Atorvastatin
      concentration was associated with SLCO1B1 c.388A>G (P<0.01) and c.521T>C (P<0.05)
      and 4beta-hydroxycholesterol, a CYP3A activity marker (adjusted R(2)=0.47). A
      second cohort of 579 patients from primary and specialty care databases were
      retrospectively genotyped. In this cohort, genotypes associated with statin
      concentration were not differently distributed among dosing groups, implying
      providers had not yet optimized each patient's risk-benefit ratio. Nearly 50% of
      patients in routine practice taking the highest doses were predicted to have
      statin concentrations greater than the 90th percentile. CONCLUSIONS:
      Interindividual variability in statin exposure in patients is associated with
      uptake and efflux transporter polymorphisms. An algorithm incorporating genomic
      and clinical variables to avoid high atorvastatin and rosuvastatin levels is
      described; further study will determine whether this approach reduces incidence
      of statin myopathy.

PMID- 23876495
TI  - Thecamoebians from Late Permian Gondwana sediments of peninsular India.
AB  - The evolutionary history of thecamoebians (testate amoebae) extends back to the
      Neoproterozoic Era. However, until now, these have had a restricted,
      discontinuous and modest record across the world. The studied sediment of
      Raniganj Formation (Godavari Graben), Andhra Pradesh, India has been assigned as
      Late Permian on the basis of co-occurring age-diagnostic Late Permian
      palynomorphs. About sixteen thecamoebian species and one taxon incertae sedis
      have been recorded here in the palynological slides on the basis of shell
      morphology and morphometry. Out of these, five belong to the family Arcellidae,
      seven to Centropyxidae, two to Trigonopyxidae, one to Difflugiidae, one to
      Plagiopyxidae, and one is regarded incertae sedis. The morphometric
      characteristics of fossil forms resemble their corresponding extant species
      studied from ecologically diverse fresh water wetlands in India. In general, the
      ratio of shell diameter and aperture diameter of Late Permian fossil and extant
      specimens show significant correlation in all the studied species. Except that,
      the ratio of shell length and breadth is the distinguishing feature between
      Centropyxis aerophila and C. aerophila 'sylvatica', rather than the ratio of
      shell length and longest diameter of the shell aperture in both fossil and extant
      forms. The study elucidates the minimal morphological evolution in thecamoebians
      and their survival during mass extinction periods and stressful environmental
      conditions over the geological timescale.

PMID- 23876493
TI  - Association between C677T polymorphism of methylene tetrahydrofolate reductase
      and congenital heart disease: meta-analysis of 7697 cases and 13,125 controls.
AB  - BACKGROUND: Association between the C677T polymorphism of the methylene
      tetrahydrofolate reductase (MTHFR) gene and congenital heart disease (CHD) is
      contentious. METHODS AND RESULTS: We compared genotypes between CHD cases and
      controls and between mothers of CHD cases and controls. We placed our results in
      context by conducting meta-analyses of previously published studies. Among 5814
      cases with primary genotype data and 10 056 controls, there was no evidence of
      association between MTHFR C677T genotype and CHD risk (odds ratio [OR], 0.96 [95%
      confidence interval, 0.87-1.07]). A random-effects meta-analysis of all studies
      (involving 7697 cases and 13 125 controls) suggested the presence of association
      (OR, 1.25 [95% confidence interval, 1.03-1.51]; P=0.022) but with substantial
      heterogeneity among contributing studies (I(2)=64.4%) and evidence of publication
      bias. Meta-analysis of large studies only (defined by a variance of the log OR
      <0.05), which together contributed 83% of all cases, yielded no evidence of
      association (OR, 0.97 [95% confidence interval, 0.91-1.03]) without significant
      heterogeneity (I(2)=0). Moreover, meta-analysis of 1781 mothers of CHD cases (829
      of whom were genotyped in this study) and 19 861 controls revealed no evidence of
      association between maternal C677T genotype and risk of CHD in offspring (OR,
      1.13 [95% confidence interval, 0.87-1.47]). There was no significant association
      between MTHFR genotype and CHD risk in large studies from regions with different
      levels of dietary folate. CONCLUSIONS: The MTHFR C677T polymorphism, which
      directly influences plasma folate levels, is not associated with CHD risk.
      Publication biases appear to substantially contaminate the literature with regard
      to this genetic association.

PMID- 23876494
TI  - Representational geometry: integrating cognition, computation, and the brain.
AB  - The cognitive concept of representation plays a key role in theories of brain
      information processing. However, linking neuronal activity to representational
      content and cognitive theory remains challenging. Recent studies have
      characterized the representational geometry of neural population codes by means
      of representational distance matrices, enabling researchers to compare
      representations across stages of processing and to test cognitive and
      computational theories. Representational geometry provides a useful intermediate
      level of description, capturing both the information represented in a neuronal
      population code and the format in which it is represented. We review recent
      insights gained with this approach in perception, memory, cognition, and action.
      Analyses of representational geometry can compare representations between models
      and the brain, and promise to explain brain computation as transformation of
      representational similarity structure. 

PMID- 23876496
TI  - Measles mortality in high and low burden districts of India: estimates from a
      nationally representative study of over 12,000 child deaths.
AB  - BACKGROUND: Direct estimates of measles mortality in India are unavailable. Our
      objective is, to use a nationally-representative study of mortality to estimate
      the number and distribution of, measles deaths in India with a focus on 264 high
      burden districts. METHODS: We used physician coded verbal autopsy data from the
      Million Death Study which surveyed, over 12,000 deaths in children aged 1 month
      to under 15 years from 1.1 million nationally, representative households in 2001
      2003. RESULTS: We estimate there were 92,000 (99% CI 63,000-137,000) measles
      deaths in children 1-59, months of age in India in 2005, representing a mortality
      rate of 3.3 (99% CI 2.3-5.0) per 1000 live, births and about 6% of all 1-59 month
      deaths. In children under 15 years of age, there were 107,000, (99% CI 74,000
      158,000) measles deaths. The measles mortality rate was nearly 70% greater in
      girls, than in boys, and 60% of the deaths were in three populous states Uttar
      Pradesh, Bihar, and Madhya, Pradesh. The 1-59 month measles mortality rate in
      high burden districts was 4.48 (99% CI 3.94-5.02) compared to 2.40 (99% CI 2.28
      2.52) per 1000 live births in other districts. CONCLUSION: Measles killed over
      100,000 children in India in 2005 and girls were at higher risk than boys. The
      majority of measles deaths occurred in a few states and high burden districts.
      The results of this study highlight the importance of focusing measles
      supplementary immunization activities in high burden districts.

PMID- 23876497
TI  - Preparation and in vitro/in vivo evaluation of fenofibrate nanocrystals.
AB  - The majority of the candidate drug entities exhibit solubility-limiting
      absorption. Nanocrystal suspensions with particle size in the nanometer scale
      (nanonization) can increase aqueous solubility and improve oral bioavailability.
      Regarding the importance of nanosuspension solidification, this study intended to
      study the critical parameters on redispersed particle size of dried nanocrystals
      as pretabletting material during spray drying process, such as supporting agents,
      inlet temperature and feed rate. Fenofibrate with poor water solubility and low
      melting point was used as a model drug. Nanocrystals of fenofibrate were prepared
      by a bead-milling method. Five types of hydrophilic excipients in combination
      with sodium dodecyl sulfate (SDS) were studied as supporting agents during spray
      drying. The resultant products were characterized by particle size analysis,
      scanning electron microscopy imaging, differential scanning calorimetry, X-ray
      powder diffraction and dissolution testing. Spray dried powder with a mean
      redispersed particle size of 699 nm was produced by using mannitol and SDS as
      supporting agent. Weight ratio (RF/m) of fenofibrate:mannitol and inlet
      temperature strongly influenced the particle size of the nanocrystals. The
      optimal inlet temperature and feed rate was optimized as 75  degrees C and 4 mL
      min(-1), respectively. Partially transformation of fenofibrate crystalline to the
      amorphous form was observed. The dissolution profiles of tablets prepared with
      the spray dried powder were similar to the commercial nanocrystal formulation
      LipidilTM ez, and faster than that of the micronized formulation. The relative
      bioavailability of the spray-dried formulation was determined to be 89.6% taking
      LipidilTM ez as the reference. There were no significant statistic differences of
      AUC0-72 and Cmax between the two formulations.

PMID- 23876498
TI  - Sildenafil citrate monohydrate-cyclodextrin nanosuspension complexes for use in
      metered-dose inhalers.
AB  - Sildenafil is a selective phosphodiesterase-5 inhibitor used for the treatment of
      erectile dysfunction and pulmonary hypertension. Sildenafil citrate monohydrate
      was complexed with alpha-, hydroxypropyl-beta- and gamma-cyclodextrin (alpha-CD,
      HP-beta-CD and gamma-CD, respectively) to enhance its water solubility. The
      complexes of sildenafil citrate monohydrate with all types of CDs were
      characterized by phase solubility diagrams, (1)H and (13)C NMR, and dielectric
      constants. Sildenafil citrate monohydrate complexed with CDs was developed as
      nanosuspensions for use in a pressurized metered-dose inhaler (pMDI). Sildenafil
      citrate monohydrate pMDI formulations were prepared by a bottom-up process using
      dried ethanol as a solvent and HFA-134a as an antisolvent and propellant in order
      to form nanosuspensions. A 3*3 factorial design was applied for the contents of
      the dried ethanol and HFA-134a propellant. The phase solubility profiles of the
      sildenafil and cyclodextrins were described as AL type with a mole ratio 1:1. The
      piperazine moiety of sildenafil formed an inclusion in the cavity of the CDs. The
      particle diameters of the sildenafil citrate monohydrate suspensions in pMDIs
      were all within a nanosuspension size range. An assay of the sildenafil content
      showed that the formation of complexes with CDs was close to 100%. In the case of
      the formulations with CDs, the emitted doses varied within 97.4+/-10.8%, the fine
      particle fractions (FPFs) were in a range of 45-81%, the fine particle dose (FPD)
      was 12.6+/-2.0 MUg and the mass median aerodynamic diameters (MMADs) were 1.86+/
      0.41 MUm. In contrast, the formulations without CDs produced a low emitted dose
      of sildenafil (<60%). Therefore, only sildenafil citrate monohydrate pMDI
      formulations containing CDs were suitable for use as aerosols.

PMID- 23876499
TI  - Nebulised siRNA encapsulated crosslinked chitosan nanoparticles for pulmonary
      delivery.
AB  - PURPOSE: To explore the potential of crosslinked chitosan nanoparticles as
      carriers for delivery of siRNA using a jet nebuliser. MATERIALS AND METHODS:
      Nanoparticles encapsulating siRNA were prepared using an ionic crosslinking
      technique at chitosan to siRNA weight/weight ratios of 10:1, 30:1 and 50:1.
      Particles were characterised for their size, charge, morphology, pH stability and
      siRNA encapsulation efficiency. Gel electrophoresis was used to assess the
      association and stability of siRNA with nanoparticles, including after
      aerosolisation using a Pari LC Sprint jet nebuliser. The aerosolisation
      properties of FITC labelled chitosan nanoparticles were investigated using a two
      stage impinger. Cell viability was performed with H-292 cells using a WST-1
      assay. RESULTS: Positively charged spherical nanoparticles were produced with
      mean diameters less than 150 nm, at all chitosan to siRNA ratios. Nanoparticles
      were non-aggregated at the pH of the airways and showed high siRNA encapsulation
      efficiency (>96%). Complete binding of siRNA to chitosan nanoparticles was
      observed when the w/w ratio was 50:1. Nebulisation produced fine particle
      fractions of 54+/-11% and 57.3+/-1.9% for chitosan and chitosan:siRNA (10:1 w/w)
      nanoparticles respectively. The stability of chitosan-encapsulated siRNA was
      maintained after nebulisation. Cell viability was high (>85%) at the highest
      chitosan concentration (83 MUg/ml). CONCLUSION: The results suggest that
      crosslinked chitosan nanoparticles have potential for siRNA delivery to the lungs
      using a jet nebuliser.

PMID- 23876500
TI  - Enhanced solubility and modified release of poorly water-soluble drugs via self
      assembled gelatin-oleic acid nanoparticles.
AB  - Recently, we synthesized novel amphiphilic gelatin-oleic acid (GO) conjugate to
      prepare self-assembled nanoparticles for drug delivery. The aim of this study was
      to investigate pharmaceutical potentialities of self-assembled GO nanoparticles
      for solubility enhancement and modified release of poorly water-soluble drugs.
      Three poorly water-soluble model drugs with different pH-dependent solubility
      (valsartan and aceclofenac, insoluble at pH 1.2; telmisartan, insoluble at pH
      6.8) were chosen to investigate the potential contributions of self-assembled GO
      nanoparticles to solubility enhancement and controlled release. The particle size
      of the drug-loaded nanoparticles was 200-250 nm. Zeta potential was calculated,
      and instrumental analysis such as powder X-ray diffraction (PXRD) and Fourier
      transform infrared (FT-IR) spectroscopy were used to investigate the
      physicochemical properties of the drug-loaded nanoparticles. Compared to the drug
      alone, the drug-loaded nanoparticles showed enhanced solubility. Furthermore, the
      release profiles of the model drugs were modified in a controlled manner. The
      current self-assembled GO nanoparticles can provide a versatile potential in drug
      delivery and tumor targeting.

PMID- 23876501
TI  - Zein-based oral drug delivery system targeting activated macrophages.
AB  - Reactive oxygen species (ROS) play an important role in the pathogenesis of
      rheumatoid arthritis (RA). ROS such as hydrogen peroxide and superoxide are
      overproduced by activated macrophages in RA. As scavengers of ROS, enzymatic
      proteins such as catalase and superoxide dismutase (SOD) have a great therapeutic
      potential; however, in vivo application is limited especially when they are
      orally administered. Although, the oral route is the most convenient for drug
      administration, therapeutic proteins are easily degraded in vivo by the harsh
      conditions of gastrointestinal (GI) tract. Here, we introduce a novel drug
      delivery system composed of zein, a plant storage protein derived from maize. We
      demonstrate that zein nanoparticles can protect therapeutic proteins, catalase
      and SOD, from the harsh conditions of GI tract. Folate-conjugated catalase or SOD
      in zein nanoparticles can target the activated macrophages and scavenge the ROS
      generated by macrophages in vitro. This novel drug delivery system will be
      applicable to other orally administered treatments based on the protective
      property in the harsh conditions of GI tract. 

PMID- 23876502
TI  - Poly(ester amide) blend microspheres for oral insulin delivery.
AB  - This study developed a novel oral insulin formulation centered on microspheres
      consisting of a blend of biodegradable poly(ester amide) (PEA). In the
      formulation, L-lysine-/L-leucine-based PEA with pendant COOH groups (PEA-COOH)
      was used as a pH-responsive material for the protection of insulin from the harsh
      environmental conditions of the stomach. Arginine-based PEA (Arg-PEA) was
      introduced to improve the intestinal absorption of the drug. The influence of
      both the hydrophobicity of PEA-COOH and the content of Arg-PEA was investigated
      in detail on microsphere surface morphology, drug loading, and the in vitro
      release profile of insulin. The PEA-COOH/Arg-PEA blend microspheres protected the
      loaded insulin in simulated gastric fluid and released insulin in a fast and
      sustained manner in simulated intestinal fluid. The in vivo test demonstrated
      that the oral administration of insulin-loaded PEA blend microspheres could
      effectively suppress the blood glucose level in diabetic rats for 10h, and the
      oral bioavailability was improved to 5.89+1.84% in healthy rats. These results
      indicate that the PEA blend microspheres are promising vehicles for the oral
      delivery of insulin.

PMID- 23876504
TI  - Phosphine in paddy fields and the effects of environmental factors.
AB  - Ambient levels of phosphine (PH3) in the air, phosphine emission fluxes from
      paddy fields and rice plants, and the distribution of matrix-bound phosphine
      (MBP) in paddy soils were investigated throughout the growing stages of rice. The
      relationships between MBP and environmental factors were analyzed to identify the
      principal factors determining the distribution of MBP. The phosphine ambient
      levels ranged from 2.368+/-0.6060 ng m(-3) to 24.83+/-6.529 ng m(-3) and averaged
      14.25+/-4.547 ng m(-3). The highest phosphine emission flux was 22.54+/-3.897 ng
      (m(2)h)(-1), the lowest flux was 7.64+/-4.83 ng (m(2)h)(-1), and the average flux
      was 14.17+/-4.977 ng (m(2)h)(-1). Rice plants transport a significant portion of
      the phosphine emitted from the paddy fields. The highest contribution rate of
      rice plants to the phosphine emission fluxes reached 73.73% and the average
      contribution was 43.00%. The average MBP content of 111.6 ng kg(-1)fluctuated
      significantly in different stages of rice growth and initially increased then
      decreased with increasing depth. The peak MBP content in each growth stage
      occurred approximately 10 cm under the surface of paddy soils. Pearson
      correlation analyses and stepwise multiple regression analysis showed that soil
      temperature (Ts), acid phosphatase (ACP) and total phosphorus (TP) were the
      principal environmental factors, with correlative rankings of Ts>ACP>TP.

PMID- 23876503
TI  - Outbreak-associated Salmonella enterica serotypes and food Commodities, United
      States, 1998-2008.
AB  - Salmonella enterica infections are transmitted not only by animal-derived foods
      but also by vegetables, fruits, and other plant products. To clarify links
      between Salmonella serotypes and specific foods, we examined the diversity and
      predominance of food commodities implicated in outbreaks of salmonellosis during
      1998-2008. More than 80% of outbreaks caused by serotypes Enteritidis,
      Heidelberg, and Hadar were attributed to eggs or poultry, whereas >50% of
      outbreaks caused by serotypes Javiana, Litchfield, Mbandaka, Muenchen, Poona, and
      Senftenberg were attributed to plant commodities. Serotypes Typhimurium and
      Newport were associated with a wide variety of food commodities. Knowledge about
      these associations can help guide outbreak investigations and control measures. 

PMID- 23876505
TI  - Hormesis and longevity with tannins: free of charge or cost-intensive?
AB  - Hormetic lifespan extension is, for obvious reasons, beneficial to an individual.
      But is this effect really cost-neutral? To answer this question, four tannic
      polyphenols were tested on the nematode Caenorhabditis elegans. All were able to
      extend the lifespan, but only some in a hormetic fashion. Additional life trait
      variables including stress resistance, reproductive behavior, growth, and
      physical fitness were observed during the exposure to the most life extending
      concentrations. These traits represent the quality of life and the population
      fitness, being the most important parameters of a hormetic treatment besides
      lifespan. Indeed, it emerged that each life-extension is accompanied by a
      constraining effect in at least one other endpoint, for example growth, mobility,
      stress resistance, or reproduction. Thus, in this context, longevity could not be
      considered to be attained for free and therefore it is likely that other hormetic
      benefits may also incur cost-intensive and unpredictable side-effects. 

PMID- 23876506
TI  - Experimental and modeling approaches for food waste composting: a review.
AB  - Composting has been used as a method to dispose food waste (FW) and recycle
      organic matter to improve soil structure and fertility. Considering the
      significance of composting in FW treatment, many researchers have paid their
      attention on how to improve FW composting efficiency, reduce operating cost, and
      mitigate the associated environmental damage. This review focuses on the overall
      studies of FW composting, not only various parameters significantly affecting the
      processes and final results, but also a number of simulation approaches that are
      greatly instrumental in well understanding the process mechanism and/or results
      prediction. Implications of many key ingredients on FW composting performance are
      also discussed. Perspects of effective laboratory experiments and computer-based
      simulation are finally investigated, demonstrating many demanding areas for
      enhanced research efforts, which include the screening of multi-functional
      additives, volatile organiccompound emission control, necessity of modeling and
      post-modeling analysis, and usefulness of developing more conjunctive AI-based
      process control techniques. 

PMID- 23876507
TI  - Two-step catalytic hydrodeoxygenation of fast pyrolysis oil to hydrocarbon liquid
      fuels.
AB  - Two-step catalytic hydrodeoxygenation (HDO) of fast pyrolysis oil was
      investigated for translating pyrolysis oil to transportation grade hydrocarbon
      liquid fuels. At the first mild HDO step, various organic solvents were employed
      to promote HDO of bio-oil to overcome coke formation using noble catalyst (Ru/C)
      under mild conditions (300  degrees C, 10 MPa). At the second deep HDO step,
      conventional hydrogenation setup and catalyst (NiMo/Al2O3) were used under severe
      conditions (400  degrees C, 13 MPa) for obtaining hydrocarbon fuel. Results show
      that the phenomenon of coke formation is effectively eliminated, and the
      properties of products have been significantly improved, such as oxygen content
      decreases from 48 to 0.5 wt% and high heating value increases from 17 to 46 MJ
      kg(-1). GC-MS analysis indicates that the final products include C11-C27
      aliphatic hydrocarbons and aromatic hydrocarbons. In short, the fast pyrolysis
      oils were successfully translated to hydrocarbon liquid fuels using a two-step
      catalytic HDO process.

PMID- 23876508
TI  - miR-320a regulates erythroid differentiation through MAR binding protein SMAR1.
AB  - Erythropoiesis is controlled by a complex interplay of several signaling pathways
      and key transcription factors, as well as microRNAs (miRNAs). MicroRNAs function
      as critical modulators of gene expression for cellular processes. In the present
      study, we found that miR-320a inhibits erythroid differentiation by targeting
      Matrix Attachment Region binding protein SMAR1. miR-320a negatively regulates the
      expression of SMAR1 by directly binding to its 3'UTR. In response to mild DNA
      damage, miR-320a expression is decreased resulting in enhanced expression of
      SMAR1 protein, which in turn, reduces its targets, Bax and Puma inhibiting
      apoptosis. Our data demonstrate that during hemin-induced erythroid
      differentiation, enhanced expression of SMAR1 negatively correlates with miR-320a
      expression. Further analysis reveals that SMAR1 regulates erythroid
      differentiation, by binding to the promoter of miR-221/222, which play a crucial
      role in early erythropoiesis. Overall, our studies provide an insight into the
      regulation of hemin mediated erythroid differentiation of K562 cells through post
      transcriptional regulation of SMAR1. 

PMID- 23876510
TI  - A unique technique for intentional occlusion of an abdominal aortic aneurysm.
AB  - We report the case of a 78-year-old man with coronary artery disease, chronic
      obstructive pulmonary disease, and chronic renal insufficiency with an enlarging
      6.7-cm infrarenal abdominal aortic aneurysm. He also had a 4-cm right common
      iliac artery aneurysm, and right external iliac artery occlusion. The patient had
      a history of an axillobifemoral bypass graft placed 10 years prior for aortoiliac
      occlusive disease. We describe the use of an infrarenal aorto-uni-iliac graft and
      subsequent intentional graft occlusion as an endovascular solution to treat
      aneurysmal disease in this sick patient. He remains asymptomatic after surgery,
      with demonstrated occlusion of his aneurysms. 

PMID- 23876509
TI  - CD34 affinity pheresis attenuates a surge among circulating progenitor cells
      following vascular injury.
AB  - BACKGROUND: Intimal hyperplasia (restenosis) is an exaggerated healing response
      leading to failure of half of vascular interventions. Increasing evidence
      suggests that circulating progenitor cells contribute to intimal pathology, and
      clinical studies have demonstrated a correlation between progenitor cells and the
      incidence of restenosis after cardiovascular interventions. The aims of this
      study were to characterize the temporal response of CD34+ progenitors following
      vascular injury in an ovine model and to evaluate an affinity pheresis approach
      to attenuate this response. METHODS: An ovine model underwent either operative
      vascular injury or a nonvascular surgery (n = 3 per group). Blood was examined
      perioperatively over 2 weeks by flow cytometry. Next, an affinity pheresis
      approach to mediate systemic depletion of CD34 progenitors was designed. Custom
      agarose pheresis matrix with antibody affinity toward CD34 or an isotype control
      was evaluated in vitro. Next, following vascular injury, sheep underwent
      perioperative whole blood volume pheresis toward either the progenitor cell
      marker CD34 (n = 3) or an isotype control (n = 4) for 14 days. Animals were
      monitored by physical exam as well as complete blood counts. Cells recovered by
      pheresis were eluted and examined by flow cytometry. RESULTS: Flow cytometry
      revealed a focal surge of circulating CD34 cells after vascular injury but not
      among surgical controls (P = .05). Toward the goal of an approach to attenuate
      the surge of CD34 progenitors, an evaluation of high-flow affinity matrix
      revealed efficacy in removal of progenitors from ovine blood in vitro. Next, a
      separate group of animals undergoing affinity pheresis after vascular injury was
      evaluated to mediate systemic depletion of CD34+ cells. Again, a surge of CD34+
      cells was observed among isotype pheresis animals following vascular intervention
      but was attenuated over 20-fold by a CD34 pheresis approach (P = .029).
      Furthermore, an average of 77 million CD34-positive cells were eluted from the
      CD34 pheresis matrix. Despite multiple sessions of pheresis, complete blood
      counts remained essentially unchanged over 2 weeks. CONCLUSIONS: Despite evidence
      suggesting a role for CD34+ circulating progenitor cells in restenotic pathology,
      the temporal pattern of CD34 progenitors after vascular injury has not been
      previously defined. We have demonstrated a surge among circulating CD34+ cells
      that appears confined to procedures involving vascular injury and that this event
      seems to occur early after vascular injury. We further conclude that CD34
      affinity pheresis attenuates the surge. This approach for direct depletion of
      progenitors may have important implications for the study of progenitors in
      vascular restenosis.

PMID- 23876511
TI  - Diet-induced obesity drives negative mouse vein graft wall remodeling.
AB  - INTRODUCTION: The heightened inflammatory phenotype associated with obesity has
      been linked to the development of cardiovascular diseases. Short-term high-fat
      feeding induces a proinflammatory state that may impact the blood vessel wall.
      CD11c, a significantly increased dendritic cell biomarker during diet-induced
      obesity (DIO), may have a mechanistic role in this high-fat feeding effect. We
      hypothesized that the proinflammatory effect of short-term DIO accelerates vein
      bypass graft failure via CD11c-dependent mechanisms. METHODS: Male 9-week-old DIO
      mice (n = 13, C57BL/6J recipients; n = 6, CD11c(-/-) recipients) and normal chow
      controls (n = 15, C57BL/6J recipients; n = 6, CD11c(-/-) recipients) underwent
      unilateral carotid interposition vein isografting (inferior vena cava from the
      same diet and genetic background donor), with a midgraft or outflow focal
      stenosis. Vein grafts were harvested at either 1 week (immunohistochemical
      staining for early CD11c expression) or 4 weeks later (morphometric analyses and
      CD11c evaluation). RESULTS: Despite a 40% larger body size, C57BL/6J DIO mice had
      44% smaller poststenosis vein graft lumens (P = .03) than their controls via an
      acceleration of overall negative vein graft wall remodeling in the day-28
      midgraft focal stenosis model but not in the outflow stenosis model. Higher CD11c
      expression occurred in DIO midgraft-stenosis vein graft walls, both at
      postoperative days 7 and 28. In contrast, with in vivo CD11c deficiency, DIO did
      not elicit this poststenotic negative remodeling but attenuated intimal
      hyperplasia. CONCLUSIONS: These findings highlight negative wall remodeling as a
      potential factor leading to vein graft failure and provide direct evidence that
      short-term dietary alterations in the mammalian metabolic milieu can have lasting
      implications related to acute vascular interventions. DIO induces negative mouse
      vein graft wall remodeling via CD11c-depedent pathways.

PMID- 23876513
TI  - A comparative study of covariance selection models for the inference of gene
      regulatory networks.
AB  - MOTIVATION: The inference, or 'reverse-engineering', of gene regulatory networks
      from expression data and the description of the complex dependency structures
      among genes are open issues in modern molecular biology. RESULTS: In this paper
      we compared three regularized methods of covariance selection for the inference
      of gene regulatory networks, developed to circumvent the problems raising when
      the number of observations n is smaller than the number of genes p. The examined
      approaches provided three alternative estimates of the inverse covariance matrix:
      (a) the 'PINV' method is based on the Moore-Penrose pseudoinverse, (b) the 'RCM'
      method performs correlation between regression residuals and (c) 'l(2C)' method
      maximizes a properly regularized log-likelihood function. Our extensive
      simulation studies showed that l(2C) outperformed the other two methods having
      the most predictive partial correlation estimates and the highest values of
      sensitivity to infer conditional dependencies between genes even when a few
      number of observations was available. The application of this method for
      inferring gene networks of the isoprenoid biosynthesis pathways in Arabidopsis
      thaliana allowed to enlighten a negative partial correlation coefficient between
      the two hubs in the two isoprenoid pathways and, more importantly, provided an
      evidence of cross-talk between genes in the plastidial and the cytosolic
      pathways. When applied to gene expression data relative to a signature of HRAS
      oncogene in human cell cultures, the method revealed 9 genes (p-value<0.0005)
      directly interacting with HRAS, sharing the same Ras-responsive binding site for
      the transcription factor RREB1. This result suggests that the transcriptional
      activation of these genes is mediated by a common transcription factor downstream
      of Ras signaling. AVAILABILITY: Software implementing the methods in the form of
      Matlab scripts are available at:
      http://users.ba.cnr.it/issia/iesina18/CovSelModelsCodes.zip.

PMID- 23876512
TI  - Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates:
      a randomized controlled trial.
AB  - INTRODUCTION: Tendon injury is a major cause of lameness and decreased
      performance in athletic equines. Various therapies for tendonitis have been
      described; however, none of these therapies results in complete tissue
      regeneration, and the injury recurrence rate is high even after long recovery
      periods involving rest and physiotherapy. METHODS: A lesion was induced with
      collagenase gel in the superficial digital flexor tendon in the center portion of
      the metacarpal region of eight equines of mixed breed. After two weeks, the
      lesions of the animals in the treated and control groups were treated through the
      intralesional administration of mesenchymal stem cells derived from adipose
      tissue (adMSCs) suspended in platelet concentrate (PC) and with phosphate
      buffered saline (PBS), respectively. Serial ultrasound analyses were performed
      every two weeks. After 16 weeks of therapy, a biopsy was performed for
      histopathological, immunohistochemical and gene expression (type I collagen
      (COL1A1), type III collagen (COL3A1), tenascin-C (TNC), tenomodulin (TNMD), and
      scleraxis (SCX)) analyses. RESULTS: Differences in the ultrasound and
      histopathological analyses were observed between the groups. Improved results
      were reported in the group treated with adMSCs suspended in PC. There was no
      difference in the gene expression levels observed after the different treatments.
      The main results observed from the histopathological evaluation of the treated
      group were as follows: a prevention of the progression of the lesion, a greater
      organization of collagen fibers, and a decreased inflammatory infiltrate. A lack
      of progression of the lesion area and its percentage was observed in the
      ultrasound image, and increased blood flow was measured by Power Doppler.
      CONCLUSIONS: The use of adMSCs combined with PC for the therapy of experimentally
      induced tendonitis prevented the progression of the tendon lesion, as observed in
      the ultrasound examination, and resulted in a greater organization and decreased
      inflammation, as observed in the histopathological evaluation. These data
      demonstrate the therapeutic potential of this therapy for the treatment of equine
      tendonitis.

PMID- 23876514
TI  - Modeling clinically relevant blast parameters based on scaling principles
      produces functional & histological deficits in rats.
AB  - Blast-induced traumatic brain injury represents a leading cause of injury in
      modern warfare with injury pathogenesis poorly understood. Preclinical models of
      blast injury remain poorly standardized across laboratories and the clinical
      relevance unclear based upon pulmonary injury scaling laws. Models capable of
      high peak overpressures and of short duration may better replicate clinical
      exposure when scaling principles are considered. In this work we demonstrate a
      tabletop shock tube model capable of high peak overpressures and of short
      duration. By varying the thickness of the polyester membrane, peak overpressure
      can be controlled. We used membranes with a thickness of 0.003, 0.005, 0.007, and
      0.010 in to generate peak reflected overpressures of 31.47, 50.72, 72.05, and
      90.10 PSI, respectively. Blast exposure was shown to decrease total activity and
      produce neural degeneration as indicated by fluoro-jade B staining. Similarly,
      blast exposure resulted in increased glial activation as indicated by an increase
      in the number of glial fibrillary acidic protein expressing astrocytes compared
      to control within the corpus callosum, the region of greatest apparent injury
      following blast exposure. Similar findings were observed with regard to activated
      microglia, some of which displayed phagocytic-like morphology within the corpus
      callosum following blast exposure, particularly with higher peak overpressures.
      Furthermore, hematoxylin and eosin staining showed the presence of red blood
      cells within the parenchyma and red, swollen neurons following blast injury.
      Exposure to blast with 90.10 PSI peak reflected overpressure resulted in
      immediate mortality associated with extensive intracranial bleeding. This work
      demonstrates one of the first examples of blast-induced brain injury in the
      rodent when exposed to a blast wave scaled from human exposure based on scaling
      principles derived from pulmonary injury lethality curves.

PMID- 23876515
TI  - Prevention of rt-PA induced blood-brain barrier component degradation by the
      poly(ADP-ribose)polymerase inhibitor PJ34 after ischemic stroke in mice.
AB  - Recombinant tissue plasminogen activator (rt-PA) is the only pharmacological
      treatment approved for thrombolysis in patients suffering from ischemic stroke,
      but its administration aggravates the risk of hemorrhagic transformations.
      Experimental data demonstrated that rt-PA increases the activity of poly(ADP
      ribose)polymerase (PARP). The aim of the present study was to investigate whether
      PJ34, a potent (PARP) inhibitor, protects the blood-brain barrier components from
      rt-PA toxicity. In our mouse model of cerebral ischemia, administration of rt-PA
      (10 mg/kg, i.v.) 6h after ischemia aggravated the post-ischemic degradation of ZO
      1, claudin-5 and VE-cadherin, increased the hemorrhagic transformations (assessed
      by brain hemoglobin content and magnetic resonance imaging). Furthermore, rt-PA
      also aggravated ischemia-induced functional deficits. Combining PJ34 with rt-PA
      preserved the expression of ZO-1, claudin-5 and VE-cadherin, reduced the
      hemorrhagic transformations and improved the sensorimotor performances. In vitro
      studies also demonstrated that PJ34 crosses the blood-brain barrier and may thus
      exert its protective effect by acting on endothelial and/or parenchymal cells.
      Thus, co-treatment with a PARP inhibitor seems to be a promising strategy to
      reduce rt-PA-induced vascular toxicity after stroke.

PMID- 23876516
TI  - Repeated immunization of mice with phosphorylated-tau peptides causes
      neuroinflammation.
AB  - The recent studies of others and of us showing robust efficacy of anti-tangle
      immunotherapy, directed against phosphorylated (phos)-tau protein, may pave the
      way to clinical trials of phos-tau immunotherapy in Alzheimer's-disease and other
      tauopathies. At this stage addressing the safety of the phos-tau-immunotherapy is
      highly needed, particularly since we have previously shown the neurotoxic
      potential of tau-immunotherapy, specifically of full-length unphosphorylated-tau
      vaccine under a CNS-proinflammatory milieu [induced by emulsification in complete
      Freund's-adjuvant (CFA) and pertussis-toxin (PT)] in young wild-type (WT)-mice.
      The aim of our current study was to address safety aspects of the phos-tau
      immunotherapy in both neurofibrillary-tangle (NFT)-mice as well as in WT-mice,
      under challenging conditions of repeated immunizations with phos-tau peptides
      under a CNS-proinflammatory milieu. NFT- and WT-mice were repeatedly immunized (7
      injections in adult-, 4 in aged-mice) with phos-tau peptides emulsified in CFA
      PT. A paralytic disease was evident in the phos-tau-immunized adult NFT-mice,
      developing progressively to 26.7% with the number of injections. Interestingly,
      the WT-mice were even more prone to develop neuroinflammation following phos-tau
      immunization, affecting 75% of the immunized mice. Aged mice were less prone to
      neuroinflammatory manifestations. Anti-phos-tau antibodies, detected in the serum
      of immunized mice, partially correlated with the neuroinflammation in WT-mice.
      This points that repeated phos-tau immunizations in the frame of a
      proinflammatory milieu may be encephalitogenic to tangle-mice, and more robustly
      to WT-mice, indicating that - under certain conditions - the safety of phos-tau
      immunotherapy is questionable. 

PMID- 23876517
TI  - No evidence for hepatitis E virus genotype 3 susceptibility in rats.

PMID- 23876518
TI  - Comparison of 2 assays for diagnosing rotavirus and evaluating vaccine
      effectiveness in children with gastroenteritis.
AB  - We compared rotavirus detection rates in children with acute gastroenteritis
      (AGE) and in healthy controls using enzyme immunoassays (EIAs) and
      semiquantitative real-time reverse transcription PCR (qRT-PCR). We calculated
      rotavirus vaccine effectiveness using different laboratory-based case definitions
      to determine which best identified the proportion of disease that was vaccine
      preventable. Of 648 AGE patients, 158 (24%) were EIA positive, and 157 were also
      qRT-PCR positive. An additional 65 (10%) were qRT-PCR positive but EIA negative.
      Of 500 healthy controls, 1 was EIA positive and 24 (5%) were qRT-PCR positive.
      Rotavirus vaccine was highly effective (84% [95% CI 71%-91%]) in EIA-positive
      children but offered no significant protection (14% [95% CI -105% to 64%]) in EIA
      negative children for whom virus was detected by qRT-PCR alone. Children with
      rotavirus detected by qRT-PCR but not by EIA were not protected by vaccination,
      suggesting that rotavirus detected by qRT-PCR alone might not be causally
      associated with AGE in all patients. 

PMID- 23876519
TI  - Healing predictors of stable juvenile osteochondritis dissecans knee lesions
      after 6 and 12 months of nonoperative treatment.
AB  - BACKGROUND: Nonoperative treatment of stable juvenile osteochondritis dissecans
      (JOCD) lesions of the knee fails in up to 50% of cases. Healing predictors are
      needed to identify potential failures and thus determine treatment options.
      PURPOSE: A predictive model for healing potential after 6 and 12 months of
      nonoperative treatment of stable JOCD lesions based on sensitive magnetic
      resonance imagining (MRI) follow-up measurements was developed. STUDY DESIGN:
      Cohort study (diagnosis); Level of evidence, 2. METHODS: A retrospective cross
      sectional study was conducted to analyze 62 white patients (76 stable JOCD
      lesions) who were initially treated by restriction of activity until they were
      free of pain. The primary end point was healing investigated on MRI with follow
      up measurements after 6 and 12 months of nonoperative treatment. Multivariate
      logistic regression was used to determine the influence of age, sex, JOCD lesion
      size, clinical symptoms, and the occurrence of cystlike lesions (CLLs) on healing
      potential. Additionally, optimal prognostic cutoffs were defined to differentiate
      failures from nonfailures. RESULTS: After 6 months of nonoperative treatment, 51
      (67%) of 76 stable JOCD lesions showed no progression toward healing or showed
      signs of instability. Normalized lesion width and area and CLL occurrence
      differed significantly between failures and nonfailures (P < .05). A multivariate
      logistic regression best-predictors model that included age, CLL size, and
      normalized lesion width best predicted healing after 6 months and resulted in an
      area under the curve (AUC) of 0.779 (P < .001). A cutoff at 48% healing
      probability, as predicted by a nomogram based on age, normalized lesion width,
      and CLL size, differentiated failures from nonfailures (sensitivity, 60.0%;
      specificity, 83.7%). After 12 months, 37 lesions (49%) had progressed toward
      healing, and the sole observation of CLL size had the highest predictive validity
      (AUC, 0.766). The optimal cutoff was a healing probability of 61% (lesion size,
      1.3 mm; sensitivity, 70.3%; specificity, 74.1%). CONCLUSION: A 6-month period of
      nonoperative treatment with or without casting might be appropriate if the
      healing potential is >48%. A 12-month period of nonoperative treatment may be
      successful if the CLL is <1.3 mm in length as assessed on MRI.

PMID- 23876520
TI  - Iatrogenic brachial plexus injuries associated with open subpectoral biceps
      tenodesis: a report of 4 cases.

PMID- 23876521
TI  - Does volume perfusion computed tomography enable differentiation of metastatic
      and non-metastatic mediastinal lymph nodes in lung cancer patients? A feasibility
      study.
AB  - OBJECTIVES: To compare the perfusion characteristics of mediastinal lymph node
      metastases with those of non-metastatic nodes in patients with newly diagnosed
      lung cancer using volume perfusion computed tomography (VPCT). MATERIALS AND
      METHODS: Between January 2010 and October 2011, 101 patients with histologically
      confirmed, untreated lung cancer received a 40-s VPCT of the tumor bulk; 32/101
      patients had evident hilar/mediastinal metastatic disease and 17/101 patients had
      proven non-metastasized lymph nodes within the VPCT scan range. Validation or
      exclusion of metastatic node involvement was proven by mediastinoscopy, biopsy,
      positron emission tomography imaging and/or unequivocal volume dynamics on follow
      up computed tomography. A total of 45 metastases and 23 non-metastatic lymph
      nodes were found within the scan range and subsequently evaluated. Blood flow
      (BF), blood volume (BV) and K(trans) were determined. Tumor volume was recorded
      as whole tumor volume. RESULTS: In a comparison between metastatic and non
      metastatic lymph nodes, we controlled for age, lymph node volume, lung tumor
      volume, lung tumor location, and histologic type effects and found no significant
      differences with respect to BF, BV, K(trans) or heterogeneity in nodal perfusion
      (P > 0.05, respectively), even after adjusting lymph node perfusion values to the
      perfusion parameters of the primary tumor (P > 0.05, respectively). Metastatic
      lymph node volume had a significant increasing effect on perfusion heterogeneity
      (P < 0.05, respectively) and BV in the primary was a highly significant factor
      for BV in metastatic disease (P < 0.001). CONCLUSION: Perfusion characteristics
      of mediastinal metastatic and non-metastatic lymph nodes in untreated lung cancer
      show considerable overlap, so that a reliable differentiation via VPCT is not
      possible.

PMID- 23876523
TI  - Cytodifferentiation of hair cells during the development of a basal chordate.
AB  - Tunicates are unique animals for studying the origin and evolution of vertebrates
      because they are considered vertebrates' closest living relatives and share the
      vertebrate body plan and many specific features. Both possess neural placodes,
      transient thickenings of the cranial ectoderm that give rise to various types of
      sensory cells, including axonless secondary mechanoreceptors. In vertebrates,
      these are represented by the hair cells of the inner ear and the lateral line,
      which have an apical apparatus typically bearing cilia and stereovilli. In
      tunicates, they are found in the coronal organ, which is a mechanoreceptor
      located at the base of the oral siphon along the border of the velum and
      tentacles and is formed of cells bearing a row of cilia and short microvilli. The
      coronal organ represents the best candidate homolog for the vertebrate lateral
      line. To further understand the evolution of secondary sensory cells, we analysed
      the development and cytodifferentiation of coronal cells in the tunicate ascidian
      Ciona intestinalis for the first time. Here, coronal sensory cells can be
      identified as early as larval metamorphosis, before tentacles form, as cells with
      short cilia and microvilli. Sensory cells gradually differentiate, acquiring hair
      cell features with microvilli containing actin and myosin VIIa; in the meantime,
      the associated supporting cells develop. The coronal organ grows throughout the
      animal's lifespan, accompanying the growth of the tentacle crown. Anti-phospho
      Histone H3 immunostaining indicates that both hair cells and supporting cells can
      proliferate. This finding contributes to the understanding of the evolution of
      secondary sensory cells, suggesting that both ancestral cell types were able to
      proliferate and that this property was progressively restricted to supporting
      cells in vertebrates and definitively lost in mammals. 

PMID- 23876522
TI  - The efficiency of design-based stereology in estimating spiral ganglion
      populations in mice.
AB  - Accurate quantification of cell populations is essential in assessing and
      evaluating neural survival and degeneration in experimental groups. Estimates
      obtained through traditional two-dimensional counting methods are heavily biased
      by the counting parameters in relation to the size and shape of the neurons to be
      counted, resulting in a large range of inaccurate counts. In contrast, counting
      every cell in a population can be extremely labor-intensive. The present study
      hypothesizes that design-based stereology provides estimates of the total number
      of cochlear spiral ganglion neurons (SGNs) in mice that are comparable to those
      obtained by other accurate cell-counting methods, such as a serial
      reconstruction, while being a more efficient method. SGNs are indispensable for
      relaying auditory information from hair cells to the auditory brainstem, and
      investigating factors affecting their degeneration provides insight into the
      physiological basis for the progression of hearing dysfunction. Stereological
      quantification techniques offer the benefits of efficient sampling that is
      independent of the size and shape of the SGNs. Population estimates of SGNs in
      cochleae from young C57 mice with normal-hearing and C57 mice with age-related
      hearing loss were obtained using the optical fractionator probe and traditional
      two-dimensional counting methods. The average estimated population of SGNs in
      normal-hearing mice was 7009, whereas the average estimated population in mice
      with age-related hearing loss was 5096. The estimated population of SGNs in
      normal-hearing mice fell within the range of values previously reported in the
      literature. The reduction in the SGN population in animals with age-related
      hearing loss was statistically significant. Stereological measurements required
      less time per section compared to two-dimensional methods while optimizing the
      amount of cochlear tissue analyzed. These findings demonstrate that design-based
      stereology provides a practical alternative to other counting methods such as the
      Abercrombie correction method, which has been shown to notably underestimate cell
      populations, and labor-intensive protocols that account for every cell
      individually. 

PMID- 23876524
TI  - Auditory filter width affects response magnitude but not frequency specificity in
      auditory cortex.
AB  - Spectral analysis of acoustic stimuli occurs in the auditory periphery (termed
      frequency selectivity) as well as at the level of auditory cortex (termed
      frequency specificity). Frequency selectivity is commonly investigated using an
      auditory filter model, while frequency specificity is often investigated as
      neural adaptation of the N1 response in electroencephalography (EEG). However,
      the effects of aging on frequency-specific adaptation, and the link between
      peripheral frequency selectivity and neural frequency specificity have not
      received much attention. Here, normal hearing younger (20-31 years) and older
      participants (49-63 years) underwent a psychophysical notched noise experiment to
      estimate individual auditory filters, and an EEG experiment to investigate
      frequency-specific adaptation in auditory cortex. The shape of auditory filters
      was comparable between age groups, and thus shows intact frequency selectivity in
      normal aging. In auditory cortex, both groups showed N1 frequency-specific neural
      adaptation effects that similarly varied with the spectral variance in the
      stimulation, while N1 responses were overall larger for older than younger
      participants. Importantly, the overall N1 amplitude, but not frequency-specific
      neural adaptation was correlated with the pass-band of the auditory filter. Thus,
      the current findings show a dissociation of peripheral frequency selectivity and
      neural frequency specificity, but suggest that widened auditory filters are
      compensated for by a response gain in frequency-specific areas of auditory
      cortex. 

PMID- 23876525
TI  - In urban South Africa, 16 year old adolescents experience greater health equality
      than children.
AB  - Despite the strongly established link between socio-economic status (SES) and
      health across most stages of the life-course, the evidence for a socio-economic
      gradient in adolescent health outcomes is less consistent. This paper examines
      associations between household, school, and neighbourhood SES measures with body
      composition outcomes in 16 year old South African Black urban adolescents from
      the 1990 born Birth to Twenty (Bt20) cohort. Multivariable regression analyses
      were applied to data from a sub-sample of the Bt20 cohort (n=346, 53% male) with
      measures taken at birth and 16 years of age to establish socio-economic,
      biological, and demographic predictors of fat mass, lean mass, and body mass
      index (BMI). Results were compared with earlier published evidence of health
      inequality at ages 9-10 years in Bt20. Consistent predictors of higher fat mass
      and BMI in fully adjusted models were being female, born post term, having a
      mother with post secondary school education, and having an obese mother. Most
      measures of SES were only weakly associated with body composition, with an
      inconsistent direction of association. This is in contrast to earlier findings
      with Bt20 9-10 year olds where SES inequalities in body composition were
      observed. Findings suggest targeting obesity interventions at females in
      households where a mother has a high BMI. 

PMID- 23876526
TI  - Advances in clinical radiobiology.

PMID- 23876527
TI  - Radiosensitising nanoparticles as novel cancer therapeutics--pipe dream or
      realistic prospect?
AB  - The field of high atomic number nanoparticle radiosensitising agents is reviewed.
      After a brief discussion of the new mode of physicochemical action implied by
      irradiation of high atomic number nanoparticles embedded in biological systems, a
      series of exemplars are discussed. Silver-, gadolinium- and gold-based
      nanoparticles are discussed in order of increasing atomic number with
      functionalisation strategies being outlined. In vitro and in vivo evidence for
      radio-enhancement and the mechanisms attributed to the increased biological
      effect are discussed.

PMID- 23876528
TI  - Understanding radiation-induced cardiovascular damage and strategies for
      intervention.
AB  - There is a clear association between therapeutic doses of thoracic irradiation
      and an increased risk of cardiovascular disease (CVD) in cancer survivors,
      although these effects may take decades to become symptomatic. Long-term
      survivors of Hodgkin's lymphoma and childhood cancers have two-fold to more than
      seven-fold increased risks for late cardiac deaths after total tumour doses of 30
      40 Gy, given in 2 Gy fractions, where large volumes of heart were included in the
      field. Increased cardiac mortality is also seen in women irradiated for breast
      cancer. Breast doses are generally 40-50 Gy in 2 Gy fractions, but only a small
      part of the heart is included in the treatment fields and mean heart doses rarely
      exceeded 10-15 Gy, even with older techniques. The relative risks of cardiac
      mortality (1.1-1.4) are consequently lower than for Hodgkin's lymphoma survivors.
      Some epidemiological studies show increased risks of cardiac death after
      accidental or environmental total body exposures to much lower radiation doses.
      The mechanisms whereby these cardiac effects occur are not fully understood and
      different mechanisms are probably involved after high therapeutic doses to the
      heart, or part of the heart, than after low total body exposures. These various
      mechanisms probably result in different cardiac pathologies, e.g. coronary artery
      atherosclerosis leading to myocardial infarct, versus microvascular damage and
      fibrosis leading to congestive heart failure. Experimental studies can help to
      unravel some of these mechanisms and may identify suitable strategies for
      managing or inhibiting CVD. In this overview, the main epidemiological and
      clinical evidence for radiation-induced CVD is summarised. Experimental data
      shedding light on some of the underlying pathologies and possible targets for
      intervention are also discussed.

PMID- 23876529
TI  - Photoswitchable fluorescent proteins: ten years of colorful chemistry and
      exciting applications.
AB  - Reversibly photoswitchable fluorescent proteins (RSFPs) are fluorescent proteins
      whose fluorescence, upon excitation at a certain wavelength, can be switched on
      or off by light in a reversible manner. In the last 10 years, many new RSFPs have
      been developed and novel applications in cell imaging discovered that rely on
      their photoswitching properties. This review will describe research on the
      mechanisms of reversible photoswitching and recent applications using RSFPs.
      While cis-trans isomerization of the chromophore is believed to be the general
      mechanism for most RSFPs, structural studies reveal diversity in the details of
      photoswitching mechanisms, including different effects of protonation,
      chromophore planarity, and pocket flexibility. Applications of RSFPs include new
      types of live-cell superresolution imaging, tracking of protein movements and
      interactions, information storage, and optical control of protein activity. 

PMID- 23876530
TI  - Should embryos developing to blastocysts on day 7 be cryopreserved and
      transferred: an analysis of pregnancy and implantation rates.
AB  - OBJECTIVE: To compare pregnancy rates (PRs) using blastocysts cryopreserved on
      day 7 with those cryopreserved on days 5 and 6. DESIGN: Retrospective
      observational cohort study. SETTING: Infertility center performing IVF.
      PATIENT(S): Eight hundred women with infertility undergoing frozen ET.
      INTERVENTION(S): Blastocysts cryopreserved on days 5, 6, and 7 after retrieval
      were thawed and transferred. MAIN OUTCOME MEASURE(S): Ongoing PRs (pregnancy
      developing appropriately into the second trimester). Thaw survival, implantation
      rates, and clinical PRs were also calculated. RESULT(S): A total of 1,406 embryos
      were thawed with a survival of 90.7% for day 5, 83.7% for day 6, and 78.7% for
      day 7. Implantation rates were 43.3%, 28.9%, and 28.9%, respectively. Ongoing PRs
      were 43.9%, 32.9%, and 26.7%, respectively. CONCLUSION(S): Blastocysts
      cryopreserved on day 7 have a lower, but clinically important potential. Embryos
      that do not achieve blastocyst stage on day 6 should not be universally
      discarded, but should be observed in culture 1 more day as 27% may result in an
      ongoing pregnancy.

PMID- 23876531
TI  - The national epidemic of multiple pregnancy and the contribution of assisted
      reproductive technology.

PMID- 23876532
TI  - Polyethylene glycated leukemia inhibitory factor antagonist inhibits human
      blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT.
AB  - OBJECTIVE: To study the effect of polyethylene glycated leukemia inhibitory
      factor (LIF) antagonist (PEGLA) in the human blastocyst viability and
      implantation process. DESIGN: In vitro study. SETTING: University hospital and
      research laboratory. PATIENT(S): Endometrial biopsy samples from fertile donors
      (n = 20), and surplus, frozen, good-quality human embryos obtained from an in
      vitro fertilization (IVF) clinic that survived thawing (n = 51). INTERVENTION(S):
      Timed human endometrial biopsy on the day of luteinizing hormone peak + 4 days
      (LH + 4). MAIN OUTCOME MEASURE(S): Human embryo attachment rate, embryo quality,
      and expression of AKT and caspase-3. RESULT(S): PEGLA significantly reduced the
      embryo attachment rate to the endometrial construct. It decreased both mRNA and
      protein for LIF in the endometrial construct. Inhibition of embryonic LIF
      triggered apoptosis. Analysis of these blastocysts by immunofluorescence and real
      time polymerase chain reaction showed a down-regulation in AKT activation and an
      increase in caspase-3 activation compared with the control group of blastocysts.
      CONCLUSION(S): The LIF inhibitor PEGLA could be a potential nonsteroidal
      fertility-regulating agent in humans. It acts on endometrial epithelial cells by
      down-regulating endometrial epithelial LIF. Inhibition of blastocyst LIF
      decreased its cell survival factor p-AKT and increased apoptosis (cleaved caspase
      3). This highlights that embryonic LIF is vital for human embryo implantation.

PMID- 23876533
TI  - Sorting of spermatozoa with flow cytometry.

PMID- 23876534
TI  - Management of the first in vitro fertilization cycle for unexplained infertility:
      a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic
      sperm injection.
AB  - OBJECTIVE: To determine the cost-effectiveness of split IVF-intracytoplasmic
      sperm injection (ICSI) for the treatment of couples with unexplained infertility.
      DESIGN: Adaptive decision model. SETTING: Academic infertility clinic.
      PATIENT(S): A total of 154 couples undergoing a split IVF-ICSI cycle and a
      computer-simulated cohort of women <35 years old with unexplained infertility
      undergoing IVF. INTERVENTION(S): Modeling insemination method in the first IVF
      cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on
      fertilization outcomes. MAIN OUTCOME MEASURE(S): Live birth rate, incremental
      cost-effectiveness ratio (ICER). RESULT(S): In a single cycle, all IVF is
      preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify
      the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is
      preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER
      of $29,666. CONCLUSION(S): In a single cycle, all IVF was preferred as the
      increased live birth rate with split IVF-ICSI and all ICSI was not justified by
      the increased cost per live birth. If two IVF cycles are needed, however, split
      IVF/ICSI becomes the preferred approach, as a result of the higher cumulative
      live birth rate compared with all IVF and the lesser cost per live birth compared
      with all ICSI.

PMID- 23876535
TI  - Comparative gene expression profiling of adult mouse ovary-derived oogonial stem
      cells supports a distinct cellular identity.
AB  - OBJECTIVE: Perform gene expression profiling of adult mouse ovary-derived
      oogonial stem cells (OSCs). DESIGN: Experimental animal study. SETTING: Research
      laboratory. ANIMAL(S): Adult C57BL/6 female mice. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Gene expression profiles were compared between freshly
      isolated and cultured OSCs, as well as between OSCs and embryonic stem cells
      (ESCs), fetal primordial germ cells (PGCs), and spermatogonial stem cells (SSCs);
      OSC yield from ovaries versus meiotic gene activation during the estrous cycle
      was determined. RESULT(S): Freshly isolated OSCs, PGCs, and SSCs exhibited
      distinct gene expression profiles. Cultured OSCs maintained their germline gene
      expression pattern but gained expression of pluripotency markers found in PGCs
      and ESCs. Cultured OSCs also expressed the meiotic marker, stimulated by retinoic
      acid gene 8 (Stra8). In vivo, OSC yield was higher from luteal versus follicular
      phase ovaries, and this was inversely related to Stra8 expression. CONCLUSION(S):
      Freshly isolated OSCs exhibit a germline gene expression profile that overlaps
      with, but is distinct from, that of PGCs and SSCs. After in vitro expansion, OSCs
      activate expression of pluripotency genes found in freshly isolated PGCs. In
      vivo, OSC numbers in the ovaries fluctuate during the estrous cycle, with the
      highest numbers noted during the luteal phase. This is followed by activation of
      Stra8 expression during the follicular phase, which may signify a wave of neo
      oogenesis to partially offset follicular loss through atresia and ovulation in
      the prior cycle.

PMID- 23876537
TI  - Progesterone luteal support after ovulation induction and intrauterine
      insemination: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effect of luteal phase P support after ovulation
      induction IUI. DESIGN: A systematic review and meta-analysis. SETTING: Not
      applicable. PATIENT(S): Undergoing ovulation induction IUI. INTERVENTION(S): Any
      form of exogenous P in ovulation induction IUI cycles. MAIN OUTCOME MEASURE(S):
      Clinical pregnancy and live birth. RESULT(S): Five trials were identified that
      met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles.
      Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98)
      and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented
      patients. These findings persisted in analyses evaluating per IUI cycle, per
      patient, and first cycle only data. In subgroup analysis, patients receiving
      gonadotropins for ovulation induction had the most increase in clinical pregnancy
      with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving
      clomiphene citrate (CC) for ovulation induction showed no difference in clinical
      pregnancy with P support (OR 0.89, 95% CI 0.47-1.67). CONCLUSION(S): Progesterone
      luteal phase support may be of benefit to patients undergoing ovulation induction
      with gonadotropins in IUI cycles. Progesterone support did not benefit patients
      undergoing ovulation induction with CC, suggesting a potential difference in
      endogenous luteal phase function depending on the method of ovulation induction.

PMID- 23876536
TI  - Serum antimullerian hormone in response to dietary management and/or physical
      exercise in overweight/obese women with polycystic ovary syndrome: secondary
      analysis of a randomized controlled trial.
AB  - OBJECTIVE: To investigate whether randomized diet and/or physical exercise
      influence serum levels of antimullerian hormone (AMH) in obese women with
      polycystic ovary syndrome (PCOS). DESIGN: Randomized, 4-month trial with three
      interventions. SETTING: Women's health clinical research unit at a university
      hospital. PATIENT(S): Fifty-seven overweight/obese women with PCOS.
      INTERVENTION(S): Diet, physical exercise, or both, using programs individually
      adapted and supervised by a dietician and/or a physiotherapist. MAIN OUTCOME
      MEASURE(S): Serum AMH levels before and after the interventions and correlations
      to reproductive function, body composition, and endocrine and metabolic
      variables. RESULT(S): After intervention, serum levels of AMH were significantly
      decreased only in the diet group, and the levels were significantly lower than in
      the exercise group. The strongest predictor of decreased AMH was a decrease in
      free T, whereas weight loss had no significant influence. Normalized levels of
      AMH were associated with improvements in menstrual cyclicity and hyperandrogenism
      but not in metabolic variables. CONCLUSION(S): This randomized study supports
      that diet reduces serum AMH in association with decreased androgen levels in
      obese women with PCOS. Increased serum AMH may be used as a marker of ovulatory
      dysfunction and hyperandrogenism but not as a marker of insulin resistance.
      CLINICAL TRIAL REGISTRY NUMBER: ISRCTN48342048.

PMID- 23876538
TI  - Parthenolide reduces cell proliferation and prostaglandin E2 [corrected] in human
      endometriotic stromal cells and inhibits development of endometriosis in the
      murine model.
AB  - OBJECTIVE: To evaluate the effects of parthenolide on human endometriotic cells
      and murine endometriotic lesions. DESIGN: Experimental study. SETTING: University
      hospital and laboratory of animal science. PATIENT(S) AND ANIMAL(S): Twenty women
      with ovarian endometrioma and 30 mice. INTERVENTION(S): Ectopic endometrial
      tissue from the endometrioma was collected. MAIN OUTCOME MEASURE(S): Human
      endometriotic stromal cells (ESCs) were pretreated with parthenolide and exposed
      to tumor necrosis factor (TNF)-alpha. Interleukin 8 (IL-8) and COX-2 gene
      expressions were evaluated by real-time reverse transcription-polymerase chain
      reaction. Interleukin-8 protein, prostaglandin E2 (PGE2) level, and intranuclear
      p65 protein concentration were determined by ELISA. Cell proliferation was
      assessed by 5-bromo-2'-deoxyuridine-ELISA. Phosphorylation of signaling pathways
      in ESCs was evaluated by Western blotting. Gene expression and proliferative
      activity in murine endometriosis-like lesions were assessed by real-time reverse
      transcription-polymerase chain reaction and Ki67 staining, respectively.
      RESULT(S): With parthenolide pretreatment, TNF-alpha-induced IL-8 gene and
      protein expression in ESCs were diminished. Tumor necrosis factor alpha-induced
      COX-2 expression and PGE2 synthesis were also inhibited. Adding parthenolide
      repressed TNF-alpha-induced 5-bromo-2'-deoxyuridine incorporation and IkappaB
      phosphorylation in ESCs. As in vivo experiments, administering parthenolide
      reduced the number, surface area, and weight, the level of Vegf, Il-6, Mcp-1, and
      Lif gene expression, and the percentage of Ki67-positive cells in murine
      endometriosis-like lesions. CONCLUSION(S): Parthenolide repressed the development
      of endometriosis by suppressing the inflammatory peritoneal environment through
      the nuclear factor kappaB pathway.

PMID- 23876539
TI  - A trial comparing the use of rectal misoprostol plus perivascular vasopressin
      with perivascular vasopressin alone to decrease myometrial bleeding at the time
      of abdominal myomectomy.
AB  - OBJECTIVE: To compare the efficacy of rectal misoprostol plus perivascular
      vasopressin with perivascular vasopressin alone as hemostatic agents for the
      reduction of blood loss during myomectomies. DESIGN: Prospective, randomized,
      double-blind, controlled study. SETTING: University of the West Indies and
      Andrews Memorial Hospital. PATIENT(S): Fifty women with symptomatic uterine
      fibroids, 25 receiving misoprostol and vasopressin and 25 receiving vasopressin
      alone before myomectomy. INTERVENTION(S): Abdominal myomectomies on patients with
      symptomatic uterine fibroids. MAIN OUTCOME MEASURE(S): Perioperative blood loss
      and febrile morbidity. RESULT(S): There were no statistically significant
      differences in sociodemographic, clinical, or myoma characteristics between the
      two groups at baseline. Postoperatively, there were no statistically significant
      differences in perioperative febrile morbidity or blood pressure between the
      groups. However, the group treated with misoprostol plus vasopressin had
      statistically significantly lower blood loss (geometric mean with 95% confidence
      interval, 334 mL [261 to 428] vs. 623 mL [354 to 1,094], a smaller change in
      hemoglobin (1.6 +/- 1.5 vs. 3.0 +/- 2.0), and a lower requirement for
      transfusion. In addition to treatment, significant determinants of blood loss
      were larger size of fibroids and greater number of fibroids. CONCLUSION(S): We
      conclude that perivascular vasopressin plus misoprostol caused a significant
      reduction in blood loss compared with perivascular vasopressin alone. CLINICAL
      TRIAL REGISTRATION NUMBER: NCT01700478.

PMID- 23876540
TI  - Sensitive ECL immunosensor for detection of retinol-binding protein based on
      double-assisted signal amplification strategy of multiwalled carbon nanotubes and
      Ru(bpy)3(2+) doped mesoporous silica nanospheres.
AB  - A novel electrochemiluminescence (ECL) strategy based on the sandwich-type
      immunosensor for sensitive detection of retinol-binding protein (RBP) was
      developed. The primary antibody anti-RBP was immobilized onto multiwalled carbon
      nanotubes (MWCNTs), which have large surface area and high electrical
      conductivity. The RBP antigen and Ru-Nafion@SiO2-labeled secondary antibody were
      then successively conjugated to form sandwich-type immunocomplexes through the
      specific interaction between antigen and antibody. The ECL signal amplification
      was significantly improved due to the synergistic effect of MWCNTs and mesoporous
      silica nanospheres (mSiO2). The developed ECL immunosensor exhibited high
      sensitivity and specificity for the detection of RBP and responded linearly to
      the clinically-relevant concentration of RBP from 78 to 5000 ng mL(-1). Moreover,
      the MWCNT-based ECL immunosensor displayed excellent stability and
      reproducibility, as well as successfully achieved the detection of RBP in patient
      urine samples with desirable results. The present work provided a promising
      technique for the clinical screening of RBP and point-of-care diagnostics.

PMID- 23876541
TI  - Graphene oxide and dextran capped gold nanoparticles based surface plasmon
      resonance sensor for sensitive detection of concanavalin A.
AB  - Carbohydrate-protein interactions mediate the important physiological and
      pathophysiological processes in living organism. Their study has attracted great
      attention due to its importance in understanding these biological processes and
      in fabricating biosensors for diagnostics and drug development. Here, by using
      concanavalin A (ConA) as a model protein, a novel surface plasmon resonance (SPR)
      sensor was developed for sensitive detection ConA. In this sensing platform,
      dextran (Dex) capped gold nanoparticles (Dex-Au NPs) were initially synthesized
      in one-pot and utilized as amplification reagent. After deposition of graphene
      oxide (GO) on the SPR gold film, phenoxy-derivatized dextran (DexP) was assembled
      onto the GO-modified gold chip surface through pi-pi interaction. The resultant
      GO/DexP sensing interface could specifically capture ConA which could further
      react with Dex-Au NPs through the specific interaction between ConA and Dex,
      forming a sandwich configuration. The morphologies and the electrochemistry of
      the formed sensing surface were investigated by using scanning electron
      microscopy and electrochemical techniques including electrochemical impedance
      spectroscopy and cyclic voltammogram. Owing to the high surface area of GO and
      the excellent amplification of Dex-Au NPs, the developed sandwich SPR sensor
      successfully fulfilled the sensitive detection of ConA in the range of 1.0-20.0
      MUg mL(-1) with a detection limit of 0.39 MUg mL(-1). Compared to the direct
      assay format, the prepared sandwich SPR sensor led to an improvement of 28.7-fold
      in the sensitivity. The results demonstrated that the proposed method might
      provide a new direction in designing high-performance SPR biosensors for
      sensitive and selective detection of a wide spectrum of biomolecules.

PMID- 23876542
TI  - A surface-scanning coil detector for real-time, in-situ detection of bacteria on
      fresh food surfaces.
AB  - Proof-in-principle of a new surface-scanning coil detector has been demonstrated.
      This new coil detector excites and measures the resonant frequency of free
      standing magnetoelastic (ME) biosensors that may now be placed outside the coil
      boundaries. With this coil design, the biosensors are no longer required to be
      placed inside the coil before frequency measurement. Hence, this new coil enables
      bacterial pathogens to be detected on fresh food surfaces in real-time and in
      situ. The new coil measurement technique was demonstrated using an E2 phage
      coated ME biosensor to detect Salmonella typhimurium on tomato surfaces. Real
      time, in-situ detection was achieved with a limit of detection (LOD)
      statistically determined to be lower than 1.5*10(3) CFU/mm(2) with a confidence
      level of difference higher than 95% (p<0.05).

PMID- 23876543
TI  - In vivo monitoring of oxidative burst on aloe under salinity stress using
      hemoglobin and single-walled carbon nanotubes modified carbon fiber
      ultramicroelectrode.
AB  - Single-walled carbon nanotubes (SWCNTs) and hemoglobin (Hb) modified carbon fiber
      ultramicroelectrode (CFUME) were employed to construct a direct electron transfer
      based in vivo H2O2 sensor. At the low working potential of -0.1 V,
      Hb/SWCNTs/CFUME showed a dynamic range up to 0.405 mM with a low detection limit
      of 4 MUM (S/N=3) and a high sensitivity of 1.07 log(A) log(M)(-1) cm(-2). The
      apparent Michaelis-Menten constant (Km, app) was estimated to be as low as 1.35
      mM. Due to the extremely small dimension and low working potential,
      Hb/SWCNTs/CFUME could give directly amperometric in vivo monitoring of H2O2 in
      aloe leaves with salt stress for 19.5h without the requirement of complex data
      processing and extra surface coatings to avoid interferences. The sharp increase
      of H2O2 level in aloe leaves with salt stress was clearly observed using
      Hb/SWCNTs/CFUME from 12.5 h, while in the aloe without salt stress, H2O2 level
      remained stable in the whole measurement. For further confirming the in vivo
      response of Hb/SWCNTs/CFUME, catalase (CAT) was injected into the spot adjacent
      to the sensor and caused rapid current decrease, which suggests the scavenging of
      H2O2. These results indicate that Hb/SWCNTs/CFUME can be a powerful tool for in
      vivo investigation of ROS.

PMID- 23876544
TI  - Distributions and sources of polychlorinated biphenyls in the coastal East China
      Sea sediments.
AB  - The Yangtze River estuary (YRE) and the adjacent East China Sea (ECS) inner shelf
      is an important sink of pollutants originated from mainland China. In this work,
      we studied the spatial and temporal variations and sources of polychlorinated
      biphenyls (PCBs) in sediments from the YRE and the ECS inner shelf. Total
      concentration of 23 PCBs (Sigma23PCB) ranged between 24.3 and 343.3 pg/g (with a
      mean value of 126.7 pg/g), and higher values occurred in the estuarine region.
      The homolog profile was dominated by 3-5Cl CBs, accounting for 76.1% of
      Sigma23PCB. The Cl proportion ranged from 45.1% to 58.8% (with a mean value of
      49.9%); the lowest level appeared in the estuarine region, and it increased with
      distance from the YRE. Lower chlorinated congeners were carried mainly by the YR
      into the ocean, to be finally buried in sediments of the estuary region and
      vicinity. However, higher chlorinated ones were imported mainly via direct
      emission from local sources, to be finally buried in sediments farther away from
      the estuary. Of the PCBs in surface sediments, 40.1% came from the YR, 37.9% from
      the local sources and the rest 22.0% from atmospheric deposition. In a sediment
      core, we found that 81% of PCBs were technically produced and 19% unintentionally
      produced in the last century. Before the 1970s, PCB levels were influenced
      predominantly by the production and consumption of technical PCBs. While in
      recent decades, the effect of human activities on PCB levels has been increasing
      continuously.

PMID- 23876545
TI  - Arsenic-tolerant, arsenite-oxidising bacterial strains in the contaminated soils
      of West Bengal, India.
AB  - As biological agents represent an affordable alternative to costly metal
      decontamination technologies, we isolated arsenic (As) oxidising bacteria from
      the As-contaminated soils of West Bengal, India. These strains were closely
      related to various species of Bacillus and Geobacillus based on their 16S rRNA
      gene sequences. They were found to be hyper-resistant to both As(V) (167-400 mM)
      and As(III) (16-47 mM). Elevated rates of As(III) oxidation (278-1250 MUM h(-1))
      and arsenite oxidase activity (2.1-12.5 nM min(-1) mg(-1) protein) were observed
      in these isolates. Screening identified four strains as superior As-oxidisers.
      Among them, AMO-10 completely (100%) oxidised 30 mM of As(III) within 24 h. The
      presence of the aoxB gene was confirmed in the screened isolates. Phylogenetic
      tree construction based on the aoxB sequence revealed that two strains, AGO-S5
      and AGH-02, clustered with Achromobacter and Variovorax, whereas the other two
      (AMO-10 and ADP-25) remained unclustered. The increased rate of As(III) oxidation
      by these native strains might be exploited for the remediation of As in
      contaminated environments. Notably, this study presents the first correlation
      regarding the presence of the aoxB gene and As(III) oxidation ability in
      Geobacillus stearothermophilus.

PMID- 23876546
TI  - Climate change scenarios for temperature and precipitation in Aragon (Spain).
AB  - By applying a two-step statistical downscaling technique to four climate models
      under different future emission scenarios, we produced future projections of the
      daily precipitation and the maximum and minimum temperatures over the Spanish
      region of Aragon. The reliability of the downscaling technique was assessed by a
      verification process involving the comparison of the downscaled reanalysis data
      with the observed data--the results were very good for the temperature and
      acceptable for the precipitation. To determine the ability of the climate models
      to simulate the real climate, their simulations of the past (the 20C3M output)
      were downscaled and then compared with the observed climate. The results are
      quite robust for temperature and less conclusive for the precipitation. The
      downscaled future projections exhibit a significant increase during the entire
      21st century of the maximum and minimum temperatures for all the considered IPCC
      future emission scenarios (A2, A1B, B1), both for mid-century (increases relative
      to the 1971-2000 averages between 1.5 degrees C and 2.5 degrees C, depending on
      the scenario) and for the end of the century (for the maximum temperature of
      approximately 3.75 degrees C, 3.3 degrees C, and 2.1 degrees C for A2, A1B, and
      B1 scenarios respectively, and for the minimum temperature of 3.1 degrees C, 2.75
      degrees C, and 1.75 degrees C). The precipitation does not follow such a clear
      tendency (and exhibits greater uncertainties), but all the scenarios suggest a
      moderate decrease in rainfall for the mid-century (2-4%) and for the end of the
      century (4.5-5.5%). Due to the clear spatial differences in climate
      characteristics, we divided the studied area into five sub-regions to analyse the
      different changes on these areas; we determined that the high mountains
      (Pyrenees, Mediterranean-Oceanic transitional climate) and the lands of the Ebro
      River Basin (Continental sub-Mediterranean climate) will probably be the most
      affected.

PMID- 23876547
TI  - Burden of diabetes mellitus and prediabetes in tribal population of India: a
      systematic review.
AB  - OBJECTIVE: To estimate the burden of diabetes mellitus and pre-diabetes in tribal
      populations of India. METHODS: The authors reviewed studies from 2000 to 2011
      that documented the prevalence of diabetes mellitus in various tribal populations
      of India. The search was performed using electronic and manual methods. Meta
      analysis of data on point prevalence was performed. RESULTS: A total of seven
      studies were retrieved. The prevalence of diabetes mellitus ranged from 0.7% to
      10.1%. The final estimate of diabetes prevalence obtained after pooling of data
      from individual studies, was 5.9% (95% CI; 3.1-9.5%). The prevalence for impaired
      fasting glucose (IFG) varied from 5.1% to 13.5% and impaired glucose tolerance
      (IGT), from 6.6% to 12.9%. CONCLUSION: Chronic disease research in tribal
      populations is limited. The reported prevalence of IFG/IGT was higher than the
      prevalence of diabetes and this observation could be suggestive of a potential
      increase in diabetes in the coming years. Given that lifestyle changes have
      occurred in the tribal populations, there is a need to synthesize evidence(s)
      relating to diabetes and other chronic diseases in these marginalized populations
      and inform policy makers.

PMID- 23876548
TI  - Association between low SIRT1 expression in visceral and subcutaneous adipose
      tissues and metabolic abnormalities in women with obesity and type 2 diabetes.
AB  - AIMS: To assess the importance of adipose tissue sirtuin 1 (SIRT1) in the
      regulation of whole-body metabolism in humans with obesity and type 2 diabetes.
      METHODS: In total, 19 non-diabetic obese women, 19 type 2 diabetic women
      undergoing gastric bypass surgery, and 27 normal-weight women undergoing
      gynecological surgery (total 65 women) were enrolled. Their anthropometric
      variables, abdominal fat distribution and metabolic parameters, serum adiponectin
      concentrations, and SIRT1 mRNA and protein and adiponectin mRNA expressions in
      visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were
      measured. RESULTS: SIRT1 mRNA levels in VAT and SAT were similar and these levels
      were suppressed in obese and type 2 diabetic women compared to normal-weight
      subjects. These decreases in SIRT1 expression were observed in both adipocytes
      and non-fat cells. There was a strong association between adipose tissue SIRT1
      mRNA and protein levels. Adipose SIRT1 expression correlated inversely with HOMA
      IR and other insulin resistance-related parameters. Adipose SIRT1 and adiponectin
      mRNA expression correlated very strongly and positively. SIRT1 mRNA level in VAT
      correlated inversely with visceral obesity whereas its expression in SAT
      correlated negatively with body mass index. CONCLUSIONS: Adipose tissue SIRT1 may
      play a key role in the regulation of whole body metabolic homeostasis in humans.
      Downregulation of SIRT1 in VAT may contribute to the metabolic abnormalities that
      are associated with visceral obesity.

PMID- 23876549
TI  - Advances in biocompatibility and physico-chemical characterization of
      microspheres for cell encapsulation.
AB  - Cell encapsulation has already shown its high potential and holds the promise for
      future cell therapies to enter the clinics as a large scale treatment option for
      various types of diseases. The advancement in cell biology towards this goal has
      to be complemented with functional biomaterials suitable for cell encapsulation.
      This cannot be achieved without understanding the close correlation between cell
      performance and properties of microspheres. The ongoing challenges in the field
      of cell encapsulation require a critical view on techniques and approaches
      currently utilized to characterize microspheres. This review deals with both
      principal subjects of microspheres characterization in the cell encapsulation
      field: physico-chemical characterization and biocompatibility. The up-to-day
      knowledge is summarized and discussed with the focus to identify missing
      knowledge and uncertainties, and to propose the mandatory next steps in
      characterization of microspheres for cell encapsulation. The primary conclusion
      of this review is that further success in development of microspheres for cell
      therapies cannot be accomplished without careful selection of characterization
      techniques, which are employed in conjunction with biological tests. 

PMID- 23876551
TI  - Peripherally inserted central catheters: use at a tertiary care pediatric center.
AB  - PURPOSE: To examine the use of peripherally inserted central catheters (PICCs) in
      a tertiary care pediatric setting. MATERIALS AND METHODS: An observational study
      of use and referral practices for PICCs in a tertiary care pediatric setting was
      performed with three distinct approaches: (i) in an institutional overview of
      trends, data from 2001 to 2012 were initially analyzed to identify high-level
      trends; (ii) an in-depth analysis of PICC referrals during 1 year was performed
      to determine details of referral patterns and clinical practices; and (iii) an
      electronic survey of the perception and understanding of referring clinical staff
      was conducted. RESULTS: During the past decade, there has been a steady increase
      in the number of PICC insertions and a decrease in median PICC dwell times.
      Discrepancies were identified between the anticipated versus actual dwell times.
      A large proportion of patients was found to have multiple PICC insertions, short
      dwell times, and premature PICC removals, potentially resulting in increasing
      risks of short- and long-term complications. Large percentages of the staff
      respondents valued the role of PICCs and had a good understanding of short-term
      complications, but underestimated the scale of the PICC service (numbers placed,
      resources involved) and several long-term complications associated with PICCs.
      CONCLUSIONS: The number of PICCs inserted in children is increasing while PICC
      dwell times are decreasing. Better postprocedure care is important to minimize
      premature removals and avoid repeat insertions. Associated complications are not
      fully appreciated by the referring pediatricians. Further education and
      guidelines are needed.

PMID- 23876552
TI  - Tunneled peritoneal drainage catheter placement for refractory ascites: single
      center experience in 188 patients.
AB  - PURPOSE: To assess the success and safety of tunneled peritoneal drainage
      catheters for the management of ascites refractory to medical management.
      MATERIALS AND METHODS: A total of 188 consecutive patients (83 male, 105 female;
      average age 59 y) with refractory ascites were treated with tunneled peritoneal
      drainage catheters from January 1, 2006, to August 10, 2012. A combination of
      fluoroscopic and ultrasound guidance was used to insert all catheters. Patient
      history, procedural records, and clinical follow-up documents were
      retrospectively reviewed. Clinical data (malignancy, renal disease, chemotherapy,
      neutropenia, albumin levels) were compared with respect to patency and
      complication rates with the use of odds ratios. Catheter survival curves were
      generated with the Kaplan-Meier method and life-table analysis for the cumulative
      and infection-free survival of primary and secondary catheters. RESULTS: A total
      of 193 catheter placements or interventions were performed in 188 patients with
      refractory ascites: 170 catheters (93%) were placed for malignant etiologies and
      13 (7%) for nonmalignant etiologies. The most common malignancies were ovarian
      (22%), pancreatic (12%), and breast (11%). The most common nonmalignant
      etiologies were end-stage liver disease (n = 7) and heart failure (n = 6). There
      was a 100% technical success rate for catheter insertion; no procedure-related
      deaths or major placement complications were identified. Catheter survival ranged
      from 0 to 796 days (mean, 60 d), with a total of 11,936 cumulative catheter-days.
      Fourteen postplacement complications were identified: five patients experienced
      catheter malfunction, four had leakage of ascites at the incisional site
      requiring suture placement, three had cellulitis of the tunnel tract, and two
      developed peritonitis. The annual complication event rate was 0.43 events per
      year (ie, 0.12 events per 100 catheter-days). Pancreatic malignancy was
      associated with a significantly increased rate of catheter malfunction (ie,
      occlusion). CONCLUSIONS: Radiologic insertion of tunneled peritoneal drainage
      catheters demonstrated a 100% technical success rate for insertion and an
      acceptable complication rate for the management of refractory ascites.

PMID- 23876553
TI  - Radiation protection in interventional radiology: survey results of attitudes and
      use.
AB  - PURPOSE: To assess attitudes of interventional radiologists toward personal
      radiation protection and the use of radiation protection devices. MATERIALS AND
      METHODS: Invitations to an anonymous online survey that comprised eight questions
      focused on operator attitudes toward radiation protection devices were sent via e
      mail to the active membership of the Society of Interventional Radiology (SIR): a
      total of 3,158 e-mail invitations. A single reminder e-mail was sent. RESULTS:
      There were 504 survey responders (16% response rate). Reported radiation safety
      device use included lead apron (99%), thyroid shield (94%), leaded eyeglasses
      (54%), ceiling-suspended leaded shield (44%), rolling leaded shields (12%),
      ceiling-suspended/rolling lead-equivalent apron (4%), radiation-attenuating
      sterile surgical gloves (1%), and sterile lead-equivalent patient-mounted drape
      (4%). Reasons commonly cited for not using certain devices were comfort
      (eyewear), ease of use (mounted shields), and lack of availability
      (rolling/hanging shields and patient-mounted shields). CONCLUSIONS:
      Interventionalists have an array of tools from which to choose for personal
      radiation protection; however, for a variety of reasons related to lack of
      availability or choice, these tools are not universally employed. Further study
      may be of value to clarify why comfort was cited most often as the primary
      barrier to the use of protective eyewear and difficulty of use was cited as the
      primary barrier to use of mounted shields (despite reporting that concern for
      radiation-induced injury to the eye is paramount). It may also be of interest to
      further study why certain devices with demonstrable protection effects are not
      readily available, such as rolling/hanging and patient-mounted shields.

PMID- 23876554
TI  - The Ca(2+) channel inhibitor efonidipine decreases voltage-dependent K(+) channel
      activity in rabbit coronary arterial smooth muscle cells.
AB  - The effect of efonidipine, a commercially available antihypertensive drug and
      Ca(2+) channel inhibitor, on voltage-dependent K(+) (Kv) channels was studied in
      freshly isolated rabbit coronary arterial smooth muscle cells using the whole
      cell patch clamp technique. The amplitude of Kv current was decreased by
      application of efonidipine in a dose-dependent manner, with IC50 of 0.26MUM and a
      Hill coefficient of 0.91, which suggests 1:1 binding stoichiometry. Efonidipine
      did not affect voltage-dependent activation of the Kv channel, but shifted the
      inactivation curve by -8.87mV. The inhibitory effect of efonidipine was not
      significantly changed by depletion of extracellular Ca(2+) or intracellular ATP,
      which indicated no involvement of the Ca(2+) channel or intracellular protein
      kinase-dependent cascades. We conclude that efonidipine dose-dependently inhibits
      Kv current in a phosphorylation- and Ca(2+) channel-independent manner. 

PMID- 23876555
TI  - Letter: Completion lymph node dissection in melanoma patients with positive
      sentinel lymph nodes: Authors' reply.

PMID- 23876556
TI  - Robotic partial nephrectomy: a promising treatment option for T1b and complex
      renal tumors?

PMID- 23876557
TI  - Traditional and complementary approaches to health for children: Modelling the
      parental decision-making process using Andersen's Sociobehavioural Model.
AB  - OBJECTIVES: Traditional and complementary approaches to health (TCA) are common
      for children. Andersen's Sociobehavioural Model (SBM) is often used to explain
      healthcare decision-making. This study aimed to identify the prevalence and
      determinants of traditional and complementary approaches to health (TCA) in a
      multi-ethnic child population, and to explore whether the SBM explained TCA
      health care decision-making in this population. DESIGN: Cross-sectional
      questionnaire survey. NHS ethical approval was given. SETTING: GP waiting rooms,
      Northwest London. MAIN OUTCOME MEASURE AND ANALYSIS: All carers/parents (with
      children under 16), attending GP appointments on specific days, were asked to
      complete a questionnaire about TCA use; primary outcome 12-month child TCA use.
      Forward stepwise logistic regression tested appropriateness of the SBM. RESULTS:
      A total of 394 questionnaires were returned, representing 737 children; a quarter
      White British. Prevalence of 12-month TCA use was 45.4%, mainly food-based
      herbs/spices for minor illnesses which were used prior to GP consultation. Over
      half identified that TCA was part of their ethnic/cultural background. Only 29%
      had discussed TCA with their GP. The strongest predictor of child TCA use in the
      SBM was carer TCA use, itself influenced by carer gender and ethnicity, and GP
      advice. Need factors were not influential. CONCLUSIONS: Child TCA use was common
      in this multi-ethnic community, particularly the use of food-based remedies for
      minor illnesses, and carers' experience and background are central in deciding to
      use TCA for a child. TCA appears practiced as part of cultural background, with
      implications for GPs to be aware of their role in guiding patients to ensure safe
      practice.

PMID- 23876558
TI  - The effectiveness of a comprehensive mind body weight loss intervention for
      overweight and obese adults: a pilot study.
AB  - OBJECTIVES: This pilot study evaluated the effectiveness of a comprehensive mind
      body intervention for weight loss in overweight and obesity and the maintenance
      of weight loss at 6-month follow-up. DESIGN: Thirty-one overweight and obese
      employees (Body Mass Index (BMI) 28.6-47.9 kg/m2) from a large corporation
      participated in a 20-week comprehensive mind body intervention targeting weight
      loss. MAIN OUTCOME MEASURES: Weight, BMI, waist and hip circumference, rate
      pressure product (RPP), blood pressure, fasting blood glucose, cholesterol,
      triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and
      psychological variables were collected at baseline, post-intervention, and 6
      month follow-up. RESULTS: Using linear mixed model analyses, the intervention
      resulted in significant mean weight loss (-4.3 kg, 95% CI -5.8 to -2.8),
      decreases in BMI (-1.51, 95% CI -2.1 to -1.0), hip circumference measurement (
      4.3 cm, 95% CI -6.9 to -1.5), and triglyceride levels (95% CI -33.1 to -4.8). In
      6-month follow-up after intervention, statistically significant improvements in
      weight, BMI and waist measurement were sustained. Participants also showed
      positive changes in self-reported psychological indices: food-related
      disinhibition, and hunger both decreased significantly (p<0.01); general self
      efficacy increased (p<0.05); positive affect increased (p<0.001); physical
      function and self-esteem increased (p<0.01); and measures of health-promoting
      behaviors on 4 subscales (health responsibility, physical activity, nutrition,
      and stress management) also showed statistically significant improvements
      (p<0.001) at post-intervention and 6-month follow-up. CONCLUSIONS: This
      comprehensive mind body intervention showed modest effects on physical,
      laboratory, and psychological outcomes, both immediately following treatment and
      at 6-month follow-up, in overweight and obese individuals.

PMID- 23876559
TI  - Cardiac autonomic response during recovery from a maximal exercise using whole
      body vibration.
AB  - OBJECTIVE: To examine the effect of passive whole-body vibration (WBV) on heart
      rate (HR) variability (HRV) during the recovery from intense exercise. DESIGN:
      Randomized, counterbalanced, crossover design SETTING: Laboratory. INTERVENTIONS:
      Twenty-three healthy male performed a bicycle exercise test to exhaustion
      followed by an active recovery period using WBV (25Hz and peak to peak
      displacement of 4mm) or passive recovery period (noWBV; 0Hz-0mm) on two separate
      days in random order. The recovery protocol consisted of six 1-min sets separated
      by 1-min inter-set rest periods in the seated position with the feet on the
      vibration platform. ECG recordings were made at baseline and during recovery at
      min 2, 4, 6, 8, 10 and 12 in both conditions. Frequency-domain measures of HRV
      were determined via power spectral analysis using fast-Fourier transform. Low
      frequency (LF; 0.04-0.15Hz) and high frequency bandwidths (HF; 0.15-0.4Hz) were
      determined. RESULTS: HR was increased in both groups (P<0.01) throughout the
      recovery. At min 2, HR was lower (P=0.05) after WVB compared to the noWBV trial.
      At min 3, the increase (P<0.05) in total power after WBV was significantly
      different (P<0.01) compared to noWBV. Normalized (nu) LF and LF/HF were increased
      (P<0.01), whereas HF nu was reduced (P<0.001) in both conditions without a
      significant group-by-time interaction (P=0.08). CONCLUSION: Passive WBV reduces
      HR and increases total power during the early recovery of intense exercise,
      despite no effect on power spectral components of HRV.

PMID- 23876560
TI  - Dilemma of integration with Western medicine - views of Traditional Chinese
      Medicine practitioners in a predominant Western medical setting.
AB  - OBJECTIVES: This study aimed to explore the in-depth views of the Traditional
      Chinese Medicine (TCM) practitioners towards Western and Chinese medicine, and
      the possible ways of integration under a predominant Western medical setting.
      DESIGN AND SETTING: Purposive, qualitative design based on focus group interviews
      of TCM practitioners in Hong Kong. PARTICIPANTS: Information-rich participants
      were recruited from a Western medicine training course for TCM practitioners. Two
      focus groups comprising 13 TCM practitioners were held before the course, and two
      others with 10 TCM practitioners after the course. RESULTS: The TCM practitioners
      were adapted to act in a supportive role to Western doctors although they
      recognized their own strengths. They highlighted the prejudice from the Western
      doctors on their diagnostic approach. The TCM practitioners felt that they were
      actually more open-minded than the Western doctors, who often discouraged the
      patients to see them. Regarding integration with Western medicine, they
      considered it as a complicated issue due to the different concepts and forms of
      integration, as well as the balance between the two types of medicine. While
      there was a concern that learning Western medicine might overshadow their TCM
      mindset, they thought that TCM had always welcomed new elements to be added into
      it over the centuries, Western medicine being no exception. CONCLUSIONS: The TCM
      practitioners are adapted to a supportive role to Western doctors under a
      predominant Western medical setting. Despite the uncertainties for collaboration,
      the TCM practitioners tend to support the trend of integration.

PMID- 23876561
TI  - A double blind randomised placebo controlled study of propolis (bee glue)
      effectiveness in the treatment of severe oral mucositis in chemotherapy treated
      children.
AB  - OBJECTIVES: Chemotherapy-induced oral mucositis (OM) is a debilitating side
      effect. In addition to standard therapy, patients often use complementary and
      alternative medicine to treat OM. DESIGN: Double blind randomised placebo
      controlled study assessing propolis (bee glue) efficacy for chemotherapy-induced
      severe OM treatment. SETTING: University Children's Hospital, University Medical
      Centre Ljubljana, Ljubljana, Slovenia. INTERVENTIONS: Paediatric patients
      undergoing chemotherapy were randomly assigned to propolis (n=19) or placebo
      groups (n=21). Patients were introduced to a unified oral care protocol and asked
      to apply propolis or placebo to vestibular mucosa twice daily. Oral mucosa was
      assessed with the Oral Assessment Guide (OAG) twice a week when the patients were
      in hospital. Patients were followed for the period of the chemotherapy or for the
      first 6 months of the chemotherapy. An OAG score of 3 was considered to be severe
      OM and analysed. MAIN OUTCOME MEASUREMENTS: Three dependent variables (a) OM
      episode frequency, (b) mean number of assessment visits, at which an OAG 3 score
      was noted, expressing mean OM duration, (c) mean number of OAG 3 scores
      expressing mean OM severity) were reduced to a single variable using principal
      component analysis. A new variable (FDS) was used as the dependent variable in
      ANCOVA model analysis to show the differences between study groups. RESULTS:
      Severe OM was seen in 42% and 48% of patients in the propolis and placebo group,
      respectively. FDS was not statistically significant between study groups
      (p=0.59). CONCLUSIONS: According to our study results, propolis cannot be
      recommended for severe OM treatment.

PMID- 23876562
TI  - National survey of yoga practitioners: mental and physical health benefits.
AB  - OBJECTIVES: To describe yoga practice and health characteristics of individuals
      who practice yoga, and to explore their beliefs regarding the effects of their
      yoga practice on their health. DESIGN: A cross-sectional design with anonymous
      online surveys. SETTING: 4307 randomly selected individuals from 15 US Iyengar
      yoga studios (n=18,160), representing 41 states; 1087 individuals responded, with
      1045 (24.3%) surveys completed. OUTCOME MEASURES: Freiberg Mindfulness Inventory,
      Mental Health Continuum (subjective well-being), Multi-factor Screener (diet),
      PROMIS sleep disturbance, fatigue, and social support, International Physical
      Activity Questionnaire. RESULTS: Age: 19-87 years (M=51.7 +/- 11.7), 84.2%
      female, 89.2% white, 87.4% well educated (>= bachelor's degree). Mean years of
      yoga practice=11.4 (+/- 7.5). BMI=12.1-49.4 (M=23.1 +/- 3.9). Levels of obesity
      (4.9%), smoking (2%), and fruit and vegetable consumption (M=6.1 +/- 1.1) were
      favorable compared to national norms. 60% reported at least one chronic/serious
      health condition, yet most reported very good (46.3%) or excellent (38.8%)
      general health. Despite high levels of depression (24.8%), nearly all were
      moderately mentally healthy (55.2%) or flourishing (43.8%). Participants agreed
      yoga improved: energy (84.5%), happiness (86.5%), social relationships (67%),
      sleep (68.5%), and weight (57.3%), and beliefs did not differ substantially
      according to race or gender. The more they practiced yoga, whether in years or in
      amount of class or home practice, the higher their odds of believing yoga
      improved their health. CONCLUSIONS: Individuals who practice yoga are not free of
      health concerns, but most believe their health improved because of yoga. Yoga
      might be beneficial for a number of populations including elderly women and those
      with chronic health conditions.

PMID- 23876563
TI  - A checklist to assess the quality of reports on spa therapy and balneotherapy
      trials was developed using the Delphi consensus method: the SPAC checklist.
AB  - OBJECTIVE: The purpose of this study was to develop a checklist of items that
      describes and measures the quality of reports of interventional trials assessing
      spa therapy. METHODS: The Delphi consensus method was used to select the number
      of items in the checklist. A total of eight individuals participated, including
      an epidemiologist, a clinical research methodologist, clinical researchers, a
      medical journalist, and a health fitness programmer. Participants ranked on a 9
      point Likert scale whether an item should be included in the checklist. RESULTS:
      Three rounds of the Delphi method were conducted to achieve consensus. The final
      checklist contained 19 items, with items related to title, place of
      implementation (specificity of spa), care provider influence, and additional
      measures to minimize the potential bias from withdrawals, loss to follow-up, and
      low treatment adherence. CONCLUSION: This checklist is simple and quick to
      complete, and should help clinicians and researchers critically appraise the
      medical and healthcare literature, reviewers assess the quality of reports
      included in systematic reviews, and researchers plan interventional trials of spa
      therapy.

PMID- 23876564
TI  - Food supplement use in the community dwelling population aged 50 and over in the
      Republic of Ireland.
AB  - OBJECTIVE: Use of food supplements in the developed world is increasing in all
      age groups. With older age, the prevalence of multimorbidity and pharmacotherapy
      increases. Aim was to explore the prevalence of food supplement use among
      population aged>=50 years in Ireland and to identify factors associated with food
      supplement use. DESIGN AND SETTING: Cross-sectional analysis of food supplements
      and medicines reported during in-home interviews by 8081 community dwelling
      participants aged>=50 years included in the first wave of the Irish Longitudinal
      Study on Ageing. RESULTS: The prevalence of regular use of food supplements was
      16.6% (95% confidence interval (CI) 15.5-17.7%) and 14.1% (95% CI 13.2-15.1%)
      reported taking food supplements and medicines concomitantly. Associate factors
      for supplement use were being female (odds ratio (OR) 2.65; 95% CI 2.30-3.06),
      retired (OR 1.49; 95% CI 1.23-1.79), a non-smoker (OR 1.47; 1.21-1.77), having
      third level or higher education (OR 1.32; 95% CI 1.10-1.57) and living alone (OR
      1.37; 1.07-1.76). Possession of private health insurance (OR 1.61; 95% CI 1.23
      2.19), reporting three or more chronic conditions (OR 2.56; 95% CI 2.01-3.27) and
      polypharmacy were also associated factors (OR 2.35; 95% CI 1.85-2.98).
      CONCLUSIONS: Food supplement use is significant among the elderly in Ireland and
      increases with age. Its use is associated with having chronic conditions and
      taking (multiple) medicines, so further study is needed to assess the
      appropriateness and risks associated with food supplement use and to examine
      further the factors influencing their differential use by men and women.

PMID- 23876565
TI  - Clinically meaningful differences in pain, disability and quality of life for
      chronic nonspecific neck pain - a reanalysis of 4 randomized controlled trials of
      cupping therapy.
AB  - OBJECTIVES: The assessment of clinically meaningful differences in patients' self
      reported outcomes has become increasingly important when interpreting the results
      of clinical studies. Although these assessments have become quite common there
      are hardly any data for nonspecific neck pain, especially in the context of
      complementary and alternative medicine. The aim of this analysis is the
      determination of minimal clinically important differences (MCID) and substantial
      clinical benefits (SCB) in patients with chronic nonspecific neck pain after
      cupping treatment. METHODS: The data set comprised a total of 200 patients with
      chronic nonspecific neck pain participating in clinical trials on cupping
      therapy. The MCID and SCB for pain intensity (VAS), neck disability index (NDI)
      and the subscale bodily pain (SF-36-BP) as well as physical component summary (SF
      36-PCS) of the SF-36 were determined using receiver operating characteristic
      (ROC) curve analysis with an adapted assessment of change in health status (SF
      36), i.e. a 5-point Likert scale ranging from "much better" to "much worse", as
      anchor. MCID derived from the ROC was the score to distinguish "somewhat better"
      from "about the same", and the SCB was the score to distinguish "much better"
      from "somewhat better". RESULTS: The calculated MCIDs were: -8mm (-21%) for VAS, 
      3 points (-10.2%) for NDI, +10 points (+20.5%) for SF-36-BP and +2.6 points
      (+7.7%) for SF-36-PCS. The SCBs were: -26.5mm (-66.8%) for VAS, -8.4 points (
      29%) for NDI, +15.5 points (+43.1%) for SF-36-BP and +5.1 points (+12.9%) for SF
      36-PCS. Accuracy of the estimations was good for MCID in general and for SCB
      regarding VAS and NDI. CONCLUSIONS: The results support the assumption that
      patients' perceptions of treatment benefits measured by VAS in these trials might
      be comparable to others in conventional therapies. For NDI and SF-36-PCS the
      estimated differences were smaller than in previous reports indicating that
      context factors such as patient characteristics and specific treatment conditions
      might play an important role. Further studies on MCIDS and SCBs for chronic
      nonspecific neck pain seem warranted.

PMID- 23876566
TI  - The Chinese medicine construct "stagnation" in mind-body connection mediates the
      effects of mindfulness training on depression and anxiety.
AB  - OBJECTIVES: Previous studies have identified different, but highly correlated
      variables explaining the effects of mindfulness training. Many of them are
      limited by tautological explanation. Under the framework of the mind-body
      connection, mindfulness training cultivates body awareness and promotes self
      management of illness. Stagnation, a concept from Chinese medicine, may help
      explain the mechanism of change in mindfulness training. METHODS: Individuals
      with depressive and anxiety symptoms (n=82) were randomized to either a
      Compassion-Mindfulness Therapy (C-MT) program or a waitlist control condition.
      The effect of stagnation as a mediator was investigated for dependent variables
      including depression, anxiety, and other physical and mental health variables.
      MAJOR OUTCOME MEASURES: Depression, anxiety, stagnation, physical distress, daily
      functioning, positive affect, negative affect. RESULTS: Compared with the
      participants in the control group, those who completed C-MT demonstrated
      significant decreases in depression, F(1, 78)=15.67, p<.001, anxiety, F(1,
      78)=7.72, p<.001, stagnation, F(1, 78)=4.96, p<.001, and other body-mind-spirit
      well-being measures. After entering the change in stagnation as the mediator, the
      effect of treatment reduced: depression (.35-.22), anxiety (.33-.05), and same
      patterns in other three secondary measures. The Sobel test was administered and
      significant reductions between group and depression (z=2.18, p=.029), anxiety
      (z=2.21, p=.027), and three secondary other measures (p<.05) were indicated.
      CONCLUSION: The study provides initial support for the role of stagnation in
      mediating changes in mindfulness training. It adds evidence to body-mind
      nondualism and offers new possibilities in studying treatment process and change
      mechanism.

PMID- 23876567
TI  - The prevalence of herb and dietary supplement use among children and adolescents
      in the United States: Results from the 2007 National Health Interview Survey.
AB  - OBJECTIVE: The purpose of this study is to examine the national prevalence of
      herb and dietary supplement usage among children and adolescents age 4-17 in the
      United States, and to identify population factors associated with usage. METHODS:
      Weighted population estimates are derived from the 2007 National Health Interview
      Child Complementary and Alternative Medicine Supplement (sample n=9417). Wald chi
      square tests are used to compare factors associated with herb and dietary
      supplement use. RESULTS: An estimated 2.9 million children and adolescents used
      herbs or dietary supplements in 2007. Pediatric herb and supplement use was more
      common among adolescents and non-Hispanic whites, and positively associated with
      parental education and household income. Children with activity limitations due
      to chronic health conditions, long-term prescription use, or relatively heavy use
      of physician services were also more likely to use herbal supplements. Echinacea
      and fish oil were most commonly used herbs and supplements. CONCLUSIONS: Children
      in the US appear to use herbs or dietary supplements at a much lower rate than
      adults. This analysis shows a pattern of moderate and appropriate herb and
      supplement use in the pediatric population.

PMID- 23876568
TI  - Profile of the complementary and alternative medicine workforce across Australia,
      New Zealand, Canada, United States and United Kingdom.
AB  - BACKGROUND: Despite the expressed demand for complementary and alternative
      medicine (CAM) services in developed countries, little is known about the CAM
      workforce in terms of supply and composition. OBJECTIVE: To describe the CAM
      workforce across five developed countries to better inform health workforce and
      health services planning, and perchance, inform debate on future public health
      and primary care policy. METHODS: Data from the Australian, New Zealand,
      Canadian, UK and US Censuses of population were interrogated for information
      pertaining to the size and characteristics of the CAM workforce. This was
      supplemented by other population-level workforce data where available. RESULTS:
      The quality and availability of population-level data on the CAM workforce vary
      substantially across nations. Of the nine CAM disciplines explored, massage
      therapy consistently comprised the largest portion of the CAM workforce, followed
      closely by chiropractic. Disciplines in shortest supply were homoeopathy in
      Australia, traditional Chinese medicine in New Zealand, and naturopathy in the
      US. Across the broader CAM workforce, practitioners were typically female, aged
      >=40 years, worked within a primary care setting, held a vocational or higher
      education level qualification, worked full-time, and earned <$1000 gross per
      week. CONCLUSIONS: This work has helped shape current understandings of the CAM
      workforce. In doing so, it will help to inform the training and continuing
      education needs of the evolving CAM workforce, and further, ensure the provision
      of a competent CAM workforce to service the needs of consumers. Addressing the
      many limitations of existing data sources will assist in meeting these needs.

PMID- 23876569
TI  - Effects of meditation on anxiety, depression, fatigue, and quality of life of
      women undergoing radiation therapy for breast cancer.
AB  - OBJECTIVE: To investigate the effects of meditation on anxiety, depression,
      fatigue, and quality of life in women who are receiving radiation therapy for
      breast cancer. DESIGN: Randomized, non-program controlled, parallel intervention
      clinical trial. SETTING: The ASAN Cancer Center located in Seoul, Korea.
      INTERVENTION: The subjects of this study included 102 female breast cancer
      patients who had undergone breast-conserving surgery; these female patients were
      randomized into equally assigned meditation control groups, with each group
      consisting of 51 patients. The test group received a total of 12 meditation
      therapy sessions during their 6-week radiation therapy period, and the control
      group underwent only a conventional radiation therapy. OUTCOME: The tools used to
      evaluate the effects of meditation were Hospital Anxiety and Depression scale,
      Revised Piper Fatigue scale, and European Organization for Research and Treatment
      of Cancer-Quality of Life Core-30. The results were analyzed based on the
      principles of intention-to-treat analysis, and, as a corollary analysis, per
      protocol analysis was conducted. RESULTS: The breast cancer patients who received
      meditation therapy compared with the non-intervention group saw improvements in
      reduction of anxiety (p=.032), fatigue (p=.030), and improvement in global
      quality of life (p=.028). CONCLUSIONS: Based on the results of this study, an
      affirmation can be made that meditation can be used as a non-invasive
      intervention treatment for improving fatigue, anxiety, quality of life, and
      emotional faculties of women with breast cancer.

PMID- 23876570
TI  - Scientific case research in complementary and alternative medicine-a review.
AB  - The description of individual cases is probably the most important didactic tool
      for teaching in medicine, especially in complementary and alternative medicine
      (CAM). However, only very rarely is the information provided in traditional
      single case reports sufficient to answer scientific questions. These reports
      typically are demonstrations of the solution to a clinical problem. To contribute
      to scientific discussion single-case research must ask critical questions whose
      answers are open. Two fundamental questions are: (1) Is my observation reliable?
      (2) Which factors, other than my treatment, may explain the observed outcome? In
      this review we will give an introduction to single-case research, as well as
      present and explain single-case designs as a tool for research and discuss their
      relevance and applicability for clinical practice in CAM. This review deals
      exclusively with single-case research on treatment effects and covers
      observational single-case studies, progressive and repetitive experimental single
      case designs, n-of-1-RCT, multiple baseline design, best case series and meta
      analysis of single-case studies. 

PMID- 23876571
TI  - A systematic review and meta-analysis of Tai Chi for osteoarthritis of the knee.
AB  - OBJECTIVES: This paper aimed to systematically review and meta-analyze the
      effectiveness of Tai Chi for osteoarthritis of the knee. METHODS: MEDLINE, the
      Cochrane Library, EMBASE, Scopus, PsycInfo and CAMBASE were screened through
      April 2013. Randomized controlled trials (RCTs) comparing Tai Chi to control
      conditions were included. Two authors independently assessed risk of bias using
      the risk of bias tool recommended by the Cochrane Back Review Group. Outcome
      measures included pain, physical functional, joint stiffness, quality of life,
      and safety. For each outcome, standardized mean differences and 95% confidence
      intervals were calculated. RESULTS: 5 RCTs with a total of 252 patients were
      included. Four studies had a low risk of bias. Analysis showed moderate overall
      evidence for short-term effectiveness for pain, physical function, and stiffness.
      Strong evidence was found for short-term improvement of the physical component of
      quality of life. No long-term effects were observed. Tai Chi therapy was not
      associated with serious adverse events. CONCLUSION: This systematic review found
      moderate evidence for short-term improvement of pain, physical function and
      stiffness in patients with osteoarthritis of the knee practicing Tai Chi.
      Assuming that Tai Chi is at least short-term effective and safe it might be
      preliminarily recommended as an adjuvant treatment for patients with
      osteoarthritis of the knee. More high quality RCTs are urgently needed to confirm
      these results.

PMID- 23876572
TI  - Plant extracts with appetite suppressing properties for body weight control: a
      systematic review of double blind randomized controlled clinical trials.
AB  - OVERVIEW: As obesity has reached epidemic proportions, the management of this
      global disease is of clinical importance. The availability and popularity of
      natural dietary supplements for the treatment of obesity has risen dramatically
      in recent years. AIMS: The aim of this paper was to assess the current evidence
      of commonly available natural supplements used to suppress appetite for obesity
      control and management in humans using a systematic search of clinical trials
      meeting an acceptable standard of evidence. METHODS: The electronic databases
      PubMed, Web of Science, Google Scholar, ScienceDirect, and MEDLINE with full text
      (via EBSCOHost) were accessed during late 2012 for randomized controlled clinical
      trials (RCTs) using natural plant extracts as interventions to treat obesity
      through appetite regulation. A quality analysis using a purpose-designed scale
      and an estimation of effect size, where data were available, was also calculated.
      The inclusion criteria included the following: sample participants classified as
      overweight or obese adults (aged 18-65 years), randomized, double blind,
      controlled design, suitable placebo/control intervention, sample size >20,
      duration of intervention >2 weeks, have measurable outcomes on appetite or food
      intake and anthropometry, and full paper in English. RESULTS: There were 14
      studies that met the inclusion criteria. The findings from published double blind
      RCTs revealed mostly inconclusive evidence that plant extracts are effective in
      reducing body weight through appetite suppression. Caralluma fimbriata extract
      and a combination supplement containing Garcinia cambogia plus Gymnema sylvestre
      were the only exceptions. CONCLUSION: According to the findings from this
      systematic review, the evidence is not convincing in demonstrating that most
      dietary supplements used as appetite suppressants for weight loss in the
      treatment of obesity are effective and safe. A balance between conclusive
      findings by double blind RCTs and advertisement is required to avoid safety
      concerns and dissatisfaction from consumers.

PMID- 23876573
TI  - The effect of complementary and alternative medicine on the quality of life of
      cancer survivors: a systematic review and meta-analyses.
AB  - PURPOSE: To assess whether quality of life (QOL) improved in cancer survivors who
      had undertaken a complementary and alternative medicine (CAM) intervention,
      compared to cancer survivors who had not. METHODS: A systematic review of
      randomised controlled trials (RCTs) was undertaken. Electronic databases
      including MEDLINE, Cochrane CENTRAL, CINAHL, PSYCHINFO, EMBASE, and
      ClinicalTrials.gov were searched from 1990 to 2012. Search terms incorporating
      the concepts of cancer survivors, QOL and various types of CAM were used.
      RESULTS: From 1767 records retrieved and screened 13 full text articles were
      included in the review. Nine studies were deemed to have a high risk, one a low
      risk, and three an unclear risk of bias. CAM interventions used incorporated
      yoga, meditation or mindfulness, energy healing, medical qigong, homoeopathy, or
      mistletoe therapy. Ten of the studies used breast cancer survivors, whilst the
      remaining three included other cancer types. The studies had mixed results either
      showing a significantly greater improvement in QOL in the intervention group
      compared to the control group, or no significant difference between groups.
      However, twelve studies were of low to moderate quality, limiting the robustness
      of findings. CONCLUSIONS: This review has identified significant gaps in the
      evidence base for the effectiveness of CAM on QOL in cancer survivors. Further
      work in this field needs to adopt more rigorous methodology to help support
      cancer survivors to actively embrace self-management and effective CAMs, without
      recommending inappropriate interventions which are of no proven benefit.

PMID- 23876574
TI  - The role of mindfulness based interventions in the treatment of obesity and
      eating disorders: an integrative review.
AB  - More than one-third of U.S. adults over the age of 20 years are classified as
      obese and nearly two-thirds are overweight or obese. The prevalence of obesity
      among U.S. children and adolescents has almost tripled since 1980, with 17% of
      all youth and children now considered obese. Nine million children aged 6-19
      years are overweight, making obesity the largest health care threat facing
      today's children. Historically, the arsenal against obesity has been primarily
      focused on interventions that increase physical activity and decrease caloric
      intake. American weight loss strategies that incorporate dietary modifications
      and exercise have proven effective in achieving weight loss, but most of the
      weight is regained over time. Mindfulness based interventions, combined with
      other traditional weight loss strategies, have the potential to offer a long
      term, holistic approach to wellness. However, research reports examining the
      complementary addition of mindfulness based approaches in the treatment obesity
      and eating disorders are relatively scarce in the empirical literature. This
      paper describes what is currently known about the role of mindfulness based
      interventions when used alone, or in combination with, other traditional
      approaches in the treatment of obesity and eating disorders. 

PMID- 23876575
TI  - In vivo effect of single oral dose of artemether against early juvenile stages of
      Schistosoma mansoni Egyptian strain.
AB  - The current treatment and control of schistosomiasis, rely on a single drug,
      praziquantel, although, it has minor activity against juvenile stages of the
      parasite. Studies have shown that artemether (ART) exhibits effects against
      juveniles of Schistosoma mansoni Liberian and Puerto Rican strains, Schistosoma
      japonicum and Schistosoma haematobium. Aiming to assess the in vivo activity of
      single oral dose of ART against early juvenile stages of S. mansoni Egyptian
      strain, this study was established. Mice were treated with ART (400 mg/kg) at two
      time points evenly spaced over the period of larval development (7 and 21 days
      post-infection; pi), and a third treatment point (day 49 pi) was included to
      elucidate when susceptibility decreases. Administration of ART on day 7 pi
      reduced the total worm burden by 85.94%. The greatest reductions were seen when
      treatment was given on day 21 pi, with total and female worm burden reductions of
      91.52% and 90.57%, respectively, and cessation of oviposition. Similar dose given
      on day 49 pi reduced total worm burden by 55.17% and female worm burden by
      66.51%. Moreover, it induced significant reduction in the tissue egg load and
      significant alterations in the oogram pattern with decreased immature eggs and
      increased dead eggs. Antipathological activities were evident in significant
      reductions in granulomata count and diameter. In conclusion, ART exhibits major
      in vivo schistosomicidal effects against the early larval migratory stages of S.
      mansoni Egyptian strain, mainly the 21-day old schistosomula, hence preventing
      disease progression and morbidity.

PMID- 23876576
TI  - Extended-spectrum beta-lactamase- and AmpC-producing enterobacteria in healthy
      broiler chickens, Germany.
AB  - During 2010, we evaluated the presence of extended-spectrum beta-lactamase- and
      AmpC-producing enterobacteria in broiler chickens at slaughter. Samples (70
      carcasses and 51 ceca) from 4 flocks were analyzed by direct plating and after
      enrichment. Extended-spectrum beta-lactamase producers were found in 88.6% and
      72.5% of carcasses and ceca, respectively; AmpC producers were found in 52.9% and
      56.9% of carcasses and ceca, respectively. Most isolates were identified as
      Escherichia coli; Enterobacter cloacae (cecum) and Proteus mirabilis (carcass)
      were found in 2 samples each. Molecular characterization revealed the domination
      of CTX-M genes; plasmidic AmpC was CIT-like. Phylogenetic grouping of E. coli
      showed types A (31.5%), B1 (20.2%), B2 (13.5%), and D (34.8%). These findings
      provide evidence that healthy broilers in Germany are a source for the
      dissemination of transmissible resistance mechanisms in enterobacteria brought
      from the rearing environment into the food chain during slaughtering. 

PMID- 23876577
TI  - Incidence of lower urinary tract symptoms in a population-based study of men and
      women.
AB  - OBJECTIVE: To report the incidence of lower urinary tract symptoms (LUTS) in a
      racially and ethnically and age-diverse U.S. population-based sample of men and
      women. MATERIALS AND METHODS: We conducted a prospective cohort study with 5
      years of follow-up. A stratified 2-stage cluster random sampling method was used
      to recruit 5502 Boston residents aged 30-79 years of black, Hispanic, or white
      race or ethnicity. Of these, 4144 (1610 men and 2534 women) completed the follow
      up protocol. The American Urological Association Symptom Index was used to define
      moderate-to-severe LUTS. RESULTS: Of the 3301 men and women with no or mild LUTS
      at baseline, the 5-year incidence of moderate-to-severe LUTS (American Urological
      Association Symptom Index >=8) was 11.4% overall and was higher for women than
      for men (13.9% vs 8.5%, P = .02). Although the incidence increased with age (P
      <.001), it had a plateau among women aged 50-70 years and then doubled to 35.0%
      among women aged >=70 years. White men had a distinctly lower incidence (7%) than
      all other sex and race subgroups (13%). CONCLUSION: Approximately 1 in 10 adults
      had newly developed LUTS at 5 years follow-up of in our study, with differences
      by sex and race or ethnicity, indicating a greater occurrence of urologic
      problems among black and Hispanic participants and women.

PMID- 23876578
TI  - Long-term oral administration of 5alpha-reductase inhibitor attenuates erectile
      function by inhibiting autophagy and promoting apoptosis of smooth muscle cells
      in corpus cavernosum of aged rats.
AB  - OBJECTIVE: To investigate the effects and mechanisms of long-term treatment of
      5alpha-reductase inhibitors (5ARIs) on erectile organ structure and function in
      aged rats. MATERIALS AND METHODS: Thirty 16-month-old male rats were assigned to
      2 groups: untreated or treated with 5ARIs. After 16 weeks, the erectile function
      was measured after electrical stimulation of the cavernous nerve. The weights and
      histopathologic features of the corpus cavernosum were examined. The levels of
      autophagy, apoptosis, and protein expression were also recorded. RESULTS: In the
      5ARI-treatment group, the plasma and intraprostatic dihydrotestosterone
      concentration was lowered by 52.1% and 57.3%, respectively, and the weight of the
      corpus cavernosum and prostate had decreased by 22.4% and 35.6%, respectively.
      The in vivo erectile response to electrical stimulation of the cavernous nerve
      had decreased significantly in the 5ARI-treatment group (P <.001). Masson's
      staining, immunohistochemistry, and Western blot all demonstrated decreased
      smooth muscle and increased collagen deposition and decreased endothelial nitric
      oxide synthase and LC3-II protein expression in the corpus cavernosum of the 5ARI
      treatment group. Using transmission electron microscopy and terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling, decreased autophagy, aggravated ultrastructural injury of mitochondria,
      and increased apoptosis were observed in the cavernous smooth muscle cells from
      the rats in the 5ARI-treatment group. CONCLUSION: Long-term 5ARI treatment did
      attenuate the erectile function of aged rats. The mechanisms might have been the
      decreased rate of autophagy and an increased rate of apoptosis in the cavernous
      smooth muscle cells, suggesting a new role for androgen in maintaining the
      structural and functional integrity of the erectile organ. Additional studies are
      necessary to demonstrate the mechanisms of dihydrotestosterone in regulating the
      autophagy and apoptosis of the cavernous smooth muscle cells.

PMID- 23876579
TI  - Editorial comment.

PMID- 23876581
TI  - Management of complex anterior urethral strictures with multistage buccal mucosa
      graft reconstruction.
AB  - OBJECTIVE: To describe the indications and outcomes of salvage urethral
      reconstruction using the combination of urethrectomy and buccal graft
      replacement. MATERIALS AND METHODS: We retrospectively identified 91 consecutive
      patients who had undergone multistage urethral reconstruction from 2003 to 2009.
      The demographic and surgical outcomes data, including the need for first stage
      revision, pre- and postoperative urine flow rates, and reconstruction failure was
      collected for all patients. RESULTS: Of the 91 patients, 51 (56%) subsequently
      underwent urethral tubularization, 17 (19%) were pending closure, and 23 (25%)
      had undergone the first stage only, with no plan for completion. The stricture
      etiology included hypospadias in 41 (45.1%), lichen sclerosus in 29 (31.9%), and
      a combination of the 2 in 10 (11%). Of the 91 patients, 54.9% had panurethral
      disease, with the remaining involving varying lengths of the anterior urethra.
      The mean follow-up was 15 months (range 12-69). A total of 17 patients (18.7%)
      required revision of their first stage, with 4 requiring >=2 repairs. Seven
      patients (7.7%) required revision of their second stage, with 2 undergoing
      multiple revisions. The urine flow rates increased on average from 6.7 mL/s
      preoperatively to 21.5 mL/s postoperatively (P <.00001). In 9 patients (9.9%)
      reconstruction failed, and they required scheduled balloon dilation or a chronic
      indwelling catheter to maintain urethral patency. CONCLUSION: Urethrectomy with
      salvage reconstruction using buccal mucosal grafts in a staged fashion is the
      optimal option for complex anterior urethral stricture resolution in these
      challenging patients. Surgical revision of the first or second stage could be
      required in up to 25% of challenging patients. Despite the high complexity and
      severity of the urethral stricture burden, a 90% success rate was achieved.

PMID- 23876582
TI  - Neglected cryptorchidism: delayed recognition of persistent mullerian duct
      syndrome and subsequent malignant degeneration.

PMID- 23876583
TI  - Development of a clinical prediction model for assessment of malignancy risk in
      Bosniak III renal lesions.
AB  - OBJECTIVE: To identify independent predictors of malignancy in Bosniak III (BIII)
      renal lesions and to build a prediction model based on readily identifiable
      clinical variables. METHODS: In this institutional review board-approved, Health
      Insurance Portability and Accountability Act (HIPAA)-compliant retrospective
      study, radiology, and hospital information systems containing data from January
      1, 1994, to August 31, 2009, were queried for adult patients (age >18 years) with
      surgically excised BIII lesions. Clinical variables and results of histopathology
      were noted. Univariate and multiple-variable logistic regression analyses were
      performed to identify potential predictors and to build a prediction model. Cross
      validation was used to assess generalizability of the model's performance, as
      characterized by concordance (c) index. RESULTS: Of the 107 lesions in 101
      patients, 59 were malignant and 48 benign. On univariate analyses, the strongest
      potential predictors of malignancy were African American race (P = .043), history
      of renal cell carcinoma (RCC; P = .026), coexisting BIII lesions (P = .032),
      coexisting Bosniak IV (BIV) lesions (P = .104), body mass index (BMI; P = .078),
      and lesion size (P <.001). A model with lesion size (odds ratio [OR] = 0.69; 95%
      confidence interval [CI] 0.58-0.82), history of RCC (9.02; CI 0.99-82.15), and
      BMI (OR 1.1; 95% CI 0.99-1.19) offered the best performance with a c-index after
      cross-validation of 0.719. Using an estimated probability of malignancy of >80%,
      the positive predictive value of the model is 92% (CI 78%-100%). CONCLUSION:
      Clinical risk factors offer modest but definite predictive ability for malignancy
      in BIII lesions. In particular, a prediction model encompassing lesion size, BMI,
      and history of RCC seems promising. Further refinements with possible inclusion
      of imaging biomarkers and validation on an independent dataset are desirable.

PMID- 23876584
TI  - Perioperative outcomes for laparoscopic and robotic compared with open
      prostatectomy using the National Surgical Quality Improvement Program (NSQIP)
      database.
AB  - OBJECTIVE: To examine contemporary outcomes of minimally invasive radical
      prostatectomy (MIRP) compared with open prostatectomy, using a national,
      prospective perioperative database reflecting diverse practice settings. METHODS:
      The National Surgical Quality Improvement Program database was queried from 2005
      to 2010 for laparoscopic or robotic prostatectomy (Current Procedural Terminology
      code 55866) and open retropubic prostatectomy (Current Procedural Terminology
      codes 55840, 55842, 55845). Perioperative outcomes examined were surgical and
      total operation duration, transfusion rates, length of stay, major morbidity
      (cardiovascular, pulmonary, renal, and infectious), and mortality. RESULTS: The
      study identified 5319 radical prostatectomies: 4036 MIRP and 1283 open. Although
      operative time was significantly longer in the MIRP group, there were
      significantly fewer perioperative blood transfusions and shorter mean length of
      stay. Major postoperative morbidity and mortality were 5% in the MIRP group and
      9% in the open group (P <.001). Age, body mass index, presence of medical
      comorbidities, and open surgical technique were all independently predictive of
      major complications and mortality on multivariate analysis. CONCLUSION: In a
      nationwide database of diverse medical centers, MIRP was associated with longer
      operative time, but a significantly decreased rate of blood transfusions, length
      of stay, perioperative complication rate, and mortality compared with open
      prostatectomy. The minimally invasive surgical approach was independently
      associated with significantly fewer complications and deaths on multivariate
      analysis. Compared with other administrative databases that capture only
      inpatient events, the National Surgical Quality Improvement Program identifies
      complications up to 30 days postoperatively, providing more detailed
      characterization of complications after prostatectomy. These data reflect
      contemporary practice patterns and suggest that MIRP can be performed with low
      perioperative morbidity.

PMID- 23876585
TI  - Editorial comment.

PMID- 23876586
TI  - The effect of antiplatelet and anticoagulant therapy on the clinical outcome of
      patients undergoing ureteroscopy.
AB  - OBJECTIVE: To determine if there is any difference in the clinical outcome for
      patients receiving aspirin, clopidogrel, and warfarin undergoing ureteroscopy and
      laser lithotripsy for urolithiasis compared with patients on no antithrombotic
      medication. METHODS: We retrospectively reviewed patients who underwent
      ureteroscopy for urolithaisis from July 1, 2005 to October 1, 2010. If patients
      continued aspirin, clopidogrel, or warfarin within 48 hours of surgery, they were
      considered to be on antithrombotic therapy. Patients not on these medications or
      those who discontinued the medications atleast 5 days before surgery comprised
      the control group. Six hundred forty-six patients met our inclusion criteria for
      analysis including 137 on aspirin alone, 17 on clopidogrel, 22 on warfarin, and
      470 in the control group. RESULTS: Patients on antiplatelet and anticoagulants
      were older and were more likely to have risk factors for thromboembolism. When
      comparing patients on aspirin, clopidogrel, or warfarin with patients not on
      these medications, there was no difference in bleeding complications or need for
      an unplanned repeat ureteroscopy. There was also no difference in complications
      within 30 days of surgery. CONCLUSION: Among patients undergoing elective
      ureteroscopy and laser lithotripsy on the antithrombotic medications aspirin,
      clopidogrel, and warfarin, the procedure was as successful, and complications
      were not increased, compared with patients on no antithrombotic medications.

PMID- 23876588
TI  - Efficacy and safety of tadalafil 5 mg once daily for lower urinary tract symptoms
      suggestive of benign prostatic hyperplasia: subgroup analyses of pooled data from
      4 multinational, randomized, placebo-controlled clinical studies.
AB  - OBJECTIVE: To assess the efficacy and safety of tadalafil, a phosphodiesterase 5
      (PDE5) inhibitor efficacious for erectile dysfunction and lower urinary tract
      symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), in population
      subgroups, using pooled data from 4 international, randomized, placebo-controlled
      studies in men with LUTS/BPH. METHODS: The safety database included 1500 men
      randomized to tadalafil 5 mg once daily or placebo for 12 weeks. Changes in total
      International Prostate Symptom Score (IPSS), IPSS-quality of life index, and BPH
      impact index were examined overall, and changes in IPSS or adverse events (AEs)
      were examined across subgroups of interest. Treatment-group differences were
      assessed using analysis of covariance. RESULTS: Results of pooled data confirmed
      that tadalafil (N = 752) resulted in significant improvements from baseline vs
      placebo (N = 746) in IPSS (mean difference -2.3; P <.001), and also in BPH impact
      index and IPSS-quality of life index (both P <.001). Subgroup analyses
      demonstrated that IPSS improvements were significant regardless of baseline LUTS
      severity (IPSS <20/>=20), age (<=65/>65 years), recent previous use of alpha
      blockers or PDE5 inhibitors, total testosterone level (<300/>=300 ng/dL), or
      prostate-specific antigen predicted prostate volume (<40/>=40 mL). [corrected]
      Rates of treatment emergent AEs were comparable between subgroups of baseline age
      (<=65/>65 years), previous PDE5 inhibitor use, and the presence or absence of pre
      existing diabetes, hypertension, or cardiovascular disease (including
      hypertension), but somewhat higher for recent previous alpha-blocker use.
      CONCLUSION: In these pooled data analyses, tadalafil 5 mg improved LUTS/BPH
      across subgroups of age, LUTS severity, testosterone levels, and prostate volume.
      Rates of AEs were similar across the subgroups assessed.

PMID- 23876589
TI  - Renal infarction associated with adrenal pheochromocytoma.
AB  - The coexistence of pheochromocytoma and renal artery stenosis had been reported
      occasionally from the possible mechanism of catecholoamine-induced vasospasm and
      extrinsic compression of renal artery in some reported cases. However, renal
      infarction caused by pheochromocytoma is an uncommon phenomenon. Herein, we
      report an interesting case of adrenal pheochromocytoma associated with renal
      artery thrombosis, which should be included in the differential diagnosis of
      pheochromocytoma patients who present with abdominal pain. 

PMID- 23876591
TI  - The use of transscrotal venography to guide treatment of a persistent grade 3
      varicocele after failure of previous microsurgical varicocelectomy and
      embolization.
AB  - Varicoceles affect approximately 15% of male patients, most of whom have
      resolution of symptoms and objective findings with microscopic subinguinal
      varicocelectomy. We present an interesting case of a 16-year-old male patient
      with persistent symptomatic varicocele despite varicocelectomy and gonadal vein
      embolization. 

PMID- 23876592
TI  - Urolithiasis in horseshoe kidney with duplex collecting system.
AB  - Horseshoe kidney is a congenital renal fusion abnormality that can be complicated
      by stones; in rare cases, it has also been associated with a duplex collecting
      system. We present images of a horseshoe kidney with a right partial duplex
      collecting system that was not detected on the preoperative computed tomography
      scan. The use of a prone-split leg position for percutaneous nephrolithotomy
      facilitated the performance of flexible ureterorenoscopy of the lower pole moiety
      and percutaneous nephrolithotomy of the upper pole moiety in 1 setting with
      complete stone clearance. 

PMID- 23876590
TI  - Imidafenacin, an antimuscarinic agent, improves nocturia and reduces nocturnal
      urine volume.
AB  - OBJECTIVE: To evaluate the efficacy of imidafenacin for nocturia and nocturnal
      polyuria in patients with overactive bladder. MATERIALS AND METHODS: A stratified
      analysis was conducted on data from a phase III randomized, double-blind,
      controlled trial of imidafenacin performed at 158 centers in Japan. The subjects
      received imidafenacin (0.1 mg) twice daily (group I) or placebo twice daily
      (group P). The 24-hour urine volume, daytime and nighttime voiding frequency, and
      volume voided/micturition were evaluated from 3-day voiding diaries recorded
      every 4 weeks during the 12-week study period. Longitudinal data analysis was
      performed, with all values expressed as the least squares mean +/- standard
      error. RESULTS: A total of 46 patients (mean age 66.54 +/- 9.38 years, 9 men and
      37 women) with nocturia and nocturnal polyuria (>33% of urine production at
      night) were enrolled. Group I (n = 35) and group P (n = 11) showed no baseline
      differences in the daily voided volume, concomitant diseases, age, or body
      weight. However, the average daily number of micturitions differed (11.22 +/-
      2.17 vs 14.45 +/- 2.85). Therefore, longitudinal data analysis was performed for
      each micturition pattern. After 12 weeks of treatment, nighttime micturition was
      significantly less frequent in group I than in group P (P = .0292), and the
      nocturnal percentage of 24-hour production was significantly smaller (P = .0053).
      The interval to the first nighttime void was significantly longer in group I than
      in group P, but no difference was found in the first nighttime voided volume.
      CONCLUSION: The novel antimuscarinic agent, imidafenacin, decreases the number of
      urinations and reduces nocturnal urine production, thereby improving both
      nocturia and nocturnal polyuria.

PMID- 23876593
TI  - Fascia lata preservation during inguinal lymphadenectomy for penile cancer:
      rationale and outcome.
AB  - OBJECTIVE: To investigate local groin recurrence and morbidity associated with
      fascia lata preservation during inguinal lymphadenectomy (LAD) for penile
      carcinoma. METHODS: Between January 2002 and December 2011, 201 inguinal
      dissections with preservation of the fascia lata were performed in 104 patients
      with clinical disease staged at <=N2. The dissection boundaries were the same as
      those for radical inguinal LAD. All superficial inguinal nodes were removed en
      bloc. The cribriform fascia near the femoral canal was divided, and the deep
      inguinal lymph nodes were dissected. The fascia lata was completely preserved and
      sutured to the subcutaneous tissue. Sartorius muscle transposition was
      eliminated. Survival and morbidity data were retrospectively analyzed, and
      survival probabilities were calculated. RESULTS: The median operative time for
      unilateral inguinal LAD was 45 minutes (range, 40-60 minutes). Median follow-up
      was 36 months (range, 10-130 months). A mean number of 12.5 nodes were removed
      per groin. One patient (1%) had a recurrence outside the borders of the fascia
      lata after 7 months of follow-up. The 3-year disease-free survival rate was 92.1%
      (100% for pN0, 91.3% for pN1, 80% for pN2, and 33.3% for pN3 disease). A total of
      59 complications (29.3%) occurred, including wound infection (2.5%), skin
      necrosis (5.5%), lymphedema (11.8%), seroma formation (1.5%), lymphocele (5%),
      paresthesia (3.5%), and deep venous thrombosis (0.5%). CONCLUSION: Inguinal
      dissections with preservation of the fascia lata for penile carcinoma patients
      without extranodal extension is as effective as the classic dissection technique
      but decreases complications related to groin dissection.

PMID- 23876594
TI  - Effects of inferior mesenteric vein flow in patients with cirrhosis.
AB  - BACKGROUND & AIMS: The inferior mesenteric vein (IMV) is detected in more than
      90% of computed tomography images. Little is known about the hemodynamic features
      of IMV as a collateral vessel in portal hypertension, or its effects in clinical
      presentation and outcome. We investigated the roles of the IMV in portal
      hemodynamics, clinical presentation, and outcomes of patients with cirrhosis.
      METHODS: We performed a prospective study of 467 patients with cirrhosis (274
      men; age, 64.6 +/- 10.9 y). We assessed hemodynamics in the IMV using Doppler
      sonography and compared these data with patients' clinical presentation and
      patient outcome. RESULTS: IMV was detected in 94 patients (20.1%); 51 patients
      had hepatopetal flow, 33 patients had hepatofugal flow, and 10 patients had to
      and-fro flow. Those with hepatofugal flow had a significantly greater number of
      ascites than those with hepatopetal flow, higher Child classification (P = .004),
      and a higher incidence of decompensated liver (51.5% vs 27.5%; P = .015) and
      rectal varices (56.3% vs 13.3%; P = .013). The incidence of gastroesophageal
      varices was lower among those with hepatofugal flow (51.5%; P = .005) or to-and
      fro flow (40%; P = .008) than those with hepatopetal flow (80.4%). IMV had
      similar effects after adjustment for liver function. There were no differences in
      the cumulative rates of survival during the median 17.2 months of follow-up
      evaluation, when the patients with and without IMV were stratified by Child
      classification. CONCLUSIONS: In patients with cirrhosis, hepatofugal flow of the
      IMV appears to increase the risk of ascites and liver decompensation but reduce
      the risk for gastroesophageal varices. Although IMV is associated with reduced
      liver function, it does not affect survival.

PMID- 23876595
TI  - Effect of Chinese herbs on CYP3A4 activity and expression in vitro.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has become
      more popular among cancer patients in the Western world, who often use Chinese
      herbs as adjuvant therapy to reduce the adverse effects of conventional
      chemotherapy. However, pharmacokinetic (PK) interactions between Chinese herbs
      and anticancer drugs can occur and have dramatic consequences for these patients.
      Currently, only a few possible PK interactions between Chinese herbs and
      conventional Western drugs have been documented. AIM OF THE STUDY: Since the drug
      metabolizing enzyme cytochrome P450 3A4 (CYP3A4) contributes to most of the PK
      interactions with (anticancer) drugs, the effect of four Chinese herbs
      (Oldenlandia diffusa, Codonopsis tangshen, Rehmannia glutinosa and Astragalus
      propinquus) on the activity and expression of CYP3A4 was investigated in vitro.
      MATERIALS AND METHODS: Ethanol and water-ethanol extracts of the four Chinese
      herbs were prepared from raw material. CYP3A4 inhibition was assessed by the use
      of SupersomesTM in a fluorescence assay. Furthermore, CYP3A4 induction was
      evaluated in a human pregnane X receptor (hPXR)-mediated CYP3A4 reporter gene
      assay and a quantitative real time PCR assay, both in human colon adenocarcinoma
      derived LS180 cells (LS180). RESULTS: Extracts of Oldenlandia diffusa, Codonopsis
      tangshen, Rehmannia glutinosa and Astragalus propinquus inhibited CYP3A4 in human
      CYP3A4 SupersomesTM (IC50 values: 17-83 ug/mL). Oldenlandia diffusa and Rehmannia
      glutinosa significantly induced PXR-mediated CYP3A4 (p<0.001). Oldenlandia
      diffusa also significantly induced CYP3A4 mRNA levels (p<0.001 at 250 ug/mL).
      CONCLUSIONS: Concomitant use of Oldenlandia diffusa and Rehmannia glutinosa could
      result in induction of CYP3A4, leading to a reduced efficacy of drugs that are
      CYP3A4 substrates and have a narrow therapeutic window. Because of the possible
      enhanced toxicity caused by CYP3A4 inhibition, clinical effects of CYP3A4
      inhibition by Astragalus propinquus and Codonopsis tangshen must also be taken
      into account. In conclusion, herb-drug interactions between Chinese herbs and
      various CYP3A4 substrates can occur. Further research to investigate the clinical
      relevance of the interactions caused by Oldenlandia diffusa, Codonopsis tangshen,
      Rehmannia glutinosa and Astragalus propinquus is required.

PMID- 23876596
TI  - In vitro and in vivo antimalarial activity and cytotoxicity of extracts and
      fractions from the leaves, root-bark and stem-bark of Triclisia gilletii.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: To evaluate the in vitro antiplasmodial activity
      and cytotoxicity, and the in vivo activity of extracts and fractions from the
      leaves, root-bark and stem-bark of Triclisia gilletii (De Wild) Staner
      (Menispermaceae), used in traditional medicine against malaria. MATERIALS AND
      METHODS: The aqueous and 80% MeOH extracts, and a series of fractions and
      subfractions from the leaves, stem and root-bark of Triclisia gilletii were
      tested in vitro for their antiplasmodial activity against a Congolese-sensitive
      strain of Plasmodium falciparum, against the chloroquine and pyrimethamine
      resistant K1 strain of Plasmodium falciparum, for cytotoxicity against MRC-5
      cells, and in vivo in mice infected with Plasmodium berghei berghei. RESULTS:
      Many samples from the three plant parts exhibited pronounced activity against the
      Congolese chloroquine-sensitive strain of Plasmodium falciparum with some IC50
      values <0.02 ug/ml, and against the K1 strain, with some IC50 <0.25; the
      selectivity was higher against the Congolese strain. At oral doses of 200 and
      400mg/kg body weight in infected mice, the aqueous, 80% methanol and total
      alkaloid extracts from the three plant parts produced more than 65% and 75%
      chemosuppression, respectively. The antiplasmodial activity of these three plant
      parts of Triclisia gilletii can at least in part be attributed to
      bisbenzylisoquinoline alkaloids, and supports its use for the treatment of
      uncomplicated malaria in traditional medicine.

PMID- 23876598
TI  - Investigations of peripheral dose for helical tomotherapy.
AB  - PURPOSE: Whenever treating a patient with percutaneous radiotherapy, a certain
      amount of dose is inevitably delivered to healthy tissue. This is mainly due to
      beam's entry and exit in the region of the target volume. In regions distant from
      the target volume, dose is delivered by leakage from the MLC and head scatter
      from the accelerator head and phantom scatter from the target volume (peripheral
      dose). Helical tomotherapy is a form of radiation therapy with a uniquely
      designed machine and delivery pattern which influence the peripheral dose. The
      goal of this work was to investigate peripheral dose in helical tomotherapy. The
      experiments were used to establish a complex characterization of the peripheral
      dose. MATERIALS AND METHODS: A 30*30*60cm(3) slab phantom and TLD-100 (Lithium
      fluoride) were used for the experiments. Treatment procedures were generated with
      the tomotherapy planning system (TPS). Additionally, procedures were created on
      the Operator Station of the tomotherapy system without a calculation of the dose
      distribution. The peripheral dose which was produced by a typical tomotherapy
      treatment plan was measured. Furthermore, these procedures were used to
      differentiate the parts of the peripheral dose in phantom scatter dose and head
      scatter and leakage dose. Additionally, the relation between peripheral dose and
      treatment time and between peripheral dose and delivered dose was investigated.
      Additionally, the peripheral dose was measured in an Alderson phantom. RESULTS:
      Distances of 30cm or more resulted in a decrease of the peripheral dose to less
      than 0.1% of the target dose. The measured doses have an offset of approximately
      1cGy in comparison to the calculated doses from the TPS. The separated head
      scatter and leakage dose was measured in the range of 1cGy for typical
      treatments. Furthermore, the investigations show a linear correlation between
      head scatter leakage dose and treatment time and between scatter dose parts and
      delivered dose. A peripheral dose of 0.28% of the target dose was measured in the
      Alderson phantom at a distance of 17.5cm from the edge of the target volume.
      CONCLUSIONS: The peripheral dose delivered by a tomotherapy treatment is
      clinically unobjectionable. The measurements confirmed a linear correlation
      between head scatter and leakage and treatment time and between scatter dose and
      delivered dose.

PMID- 23876597
TI  - Perinatally administered bisphenol a as a potential mammary gland carcinogen in
      rats.
AB  - BACKGROUND: Environmental exposure to bisphenol A (BPA) affects mammary gland
      development in rodents and primates. Prenatal exposure to environmentally
      relevant doses of BPA increased the number of intraductal hyperplasias and ductal
      carcinomas in situ by 50 days of age in Wistar-Furth rats. OBJECTIVE: We aimed to
      determine whether BPA exposure of dams during gestation only or throughout
      lactation affects the incidence of mammary gland neoplasia in female offspring.
      METHODS: We treated pregnant Sprague-Dawley rats with BPA at 0, 0.25, 2.5, 25, or
      250 MUg BPA/kg BW/day from gestational day (GD) 9 to birth and from GD9 to
      postnatal day (PND) 21. Mammary glands from BPA-exposed offspring were examined
      at four time points for preneoplastic and neoplastic lesions. To assess
      circulating BPA levels, we exposed pregnant rats to vehicle or 250 MUg BPA/kg
      BW/day during gestation only or during gestation/lactation and analyzed sera from
      dams, fetuses, and nursing pups for total and unconjugated BPA. RESULTS: Total
      and unconjugated BPA were detected in sera from 100% of dams and fetuses and 33%
      of pups exposed to 250 MUg BPA/kg BW/day. Unconjugated BPA levels in exposed dams
      and fetuses (gestational) and in exposed dams and pups (gestational/lactational)
      were within levels found in humans. Preneoplastic lesions developed in BPA
      exposed female offspring across all doses as early as PND50. Unexpectedly,
      mammary gland adenocarcinomas developed in BPA-exposed offspring by PND90.
      CONCLUSIONS: Our findings suggest that developmental exposure to environmentally
      relevant levels of BPA during gestation and lactation induces mammary gland
      neoplasms in the absence of any additional carcinogenic treatment. Thus, BPA may
      act as a complete mammary gland carcinogen.

PMID- 23876599
TI  - Xerostomia is associated with old age and poor appetite in patients on chronic
      hemodialysis.
AB  - OBJECTIVE: The objective of this study was to assess variables associated with
      xerostomia in patients on chronic hemodialysis (HD). DESIGN AND METHODS: This was
      a cross-sectional study of 75 HD patients at an outpatient HD service.
      Demographic, clinical (renal disease, HD regimen/duration, Charlson comorbidity
      index, activities of daily living, instrumental activities of daily living
      [IADL], body mass index), and laboratory (hemoglobin, albumin, interleukin-6 [IL
      6], and parathyroid hormone) parameters were recorded. We assessed the appetite
      through the Hemodialysis Study Appetite questionnaire and xerostomia through the
      Xerostomia Inventory (XI). A single question ("How often does your mouth feel
      dry?"; never = Class 1, almost never = Class 2, occasionally = Class 3, often =
      Class 4, very often = Class 5) was also included in the study questionnaire. MAIN
      OUTCOME MEASURE: The main outcome measure was factors correlated with XI.
      RESULTS: The median XI score was 18 (min-max = 11-33). Forty patients had an XI
      score of 18 or less (Group 1) and between 18 and 35 (Group 2). In Group 2, age,
      Charlson comorbidity index score, and number of patients with poor/very poor
      appetite were significantly higher. At the univariate analysis, the score of the
      XI was significantly associated with age, appetite, IADL, Charlson comorbidity
      index, and serum IL-6 levels. Multiple linear regression analysis showed that the
      XI was independently associated with age and appetite. Thirty-one patients were
      in Class 1 to 2, 23 were in Class 3, and 21 were in Class 4 to 5. In Classes 4 to
      5, age and the number of patients with poor/very poor appetite were higher (P =
      .012 and .09, respectively). CONCLUSION: Xerostomia is associated with old age
      and poor appetite in patients on chronic HD.

PMID- 23876601
TI  - Molecular monitoring of chronic myeloid leukemia: international standardization
      of BCR-ABL1 quantitation.
AB  - The BCR-ABL1 translocation is a hallmark of chronic myeloid leukemia. Because
      patients treated with imatinib and other tyrosine kinase inhibitors achieve lower
      levels of detectable disease, quantitation of BCR-ABL1 transcripts with
      quantitative RT-PCR has become an essential tool in chronic myeloid leukemia
      monitoring. The prognostic significance of molecular responses was recently
      established by large-scale clinical trials. Achieving defined levels of BCR-ABL1
      on the International Scale within specific time frames is an important measure
      for assessing patient response and probability for relapse and progression.
      However, extensive variation in quantitative RT-PCR procedures and reporting
      makes it difficult to interpret these results. More important, lack of
      standardization, particularly in the United States, prevents the comparison of
      individual patient results to the data from the clinical trials, which thereby
      prohibits the meaningful use of such results in the direction of patient care. In
      this article, we will present an overview of the clinical trial discoveries that
      drive the need for standardization, review the most updated monitoring guidelines
      by the National Comprehensive Cancer Network, and highlight recommendations for
      laboratory practice regarding internal controls and reference materials. Finally,
      we will provide an update on the recent efforts in the standardization of
      quantitative RT-PCR reporting using the International Scale. 

PMID- 23876600
TI  - Vitamin D deficiency and mortality in patients receiving dialysis: the
      Comprehensive Dialysis Study.
AB  - OBJECTIVE: Although several studies have shown poorer survival among individuals
      with 25-hydroxy (OH) vitamin D deficiency, data on patients receiving dialysis
      are limited. Using data from the Comprehensive Dialysis Study (CDS), we tested
      the hypothesis that patients new to dialysis with low serum concentrations of 25
      OH vitamin D would experience higher mortality and hospitalizations. DESIGN: The
      CDS is a prospective cohort study.We recruited participants from 56 dialysis
      units located throughout the United States. SUBJECTS AND INTERVENTION: We
      obtained data on demographics, comorbidites, and laboratory values from the CDS
      Patient Questionnaire as well as the Medical Evidence Form (CMS form 2728).
      Participants provided baseline serum samples for 25-OH vitamin D measurements.
      MAIN OUTCOME MEASURE: We ascertained time to death and first hospitalization as
      well as number of first-year hospitalizations via the U.S. Renal Data System
      standard analysis files. We used Cox proportional hazards to determine the
      association between 25-OH vitamin D tertiles and survival and hospitalization.
      For number of hospitalizations in the first year, we used negative binomial
      regression. RESULTS: The analytic cohort was composed of 256 patients with
      Patient Questionnaire data and 25-OH vitamin D concentrations. The mean age of
      participants was 62 (+/-14.0) years, and mean follow-up was 3.8 years. Patients
      with 25-OH vitamin D concentrations in the lowest tertile (<10.6 ng/mL) at the
      start of dialysis experienced higher mortality (adjusted hazard ratio 1.75, 95%
      confidence interval [CI] 1.03-2.97) as well as hospitalization (adjusted hazard
      ratio 1.76, 95% CI 1.24-2.49). Patients in the lower 2 tertiles (<15.5 ng/mL)
      experienced a higher rate of hospitalizations in the first year (incidence rate
      ratio 1.70 [95% CI 1.06-2.72] for middle tertile, 1.66 [95% CI 1.10-2.51] for
      lowest tertile). CONCLUSION: We found a sizeable increase in mortality and
      hospitalization for patients on dialysis with severe 25-OH vitamin D deficiency.

PMID- 23876602
TI  - Norovirus GII.4/Sydney/2012 in Italy, winter 2012-2013.

PMID- 23876603
TI  - The interface of hypothalamic-pituitary-adrenocortical axis and circulating brain
      natriuretic peptide in prediction of cardiopulmonary performance during physical
      stress.
AB  - Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of
      hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors.
      However, HPA axis activation in different physical stress models and its
      interface with NT-pro-BNP in the prediction of cardiopulmonary performance is
      unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary
      parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20
      sedentary age-matched subjects (C). Plasma levels of NT-pro-BNP, cortisol and
      adrenocorticotropic hormone (ACTH) were measured using immunoassay sandwich
      technique, radioimmunoassay and radioimmunometric techniques, respectively, 10min
      before test (1), at beginning (2), at maximal effort (3), at 3rdmin of recovery
      (4). In all groups, NT-pro-BNP decreased between 1 and 2; increased from 2 to 3;
      and remained unchanged until 4. ACTH increased from 1 to 4, whereas cortisol
      increased from 1 to 3 and stayed elevated at 4. In all groups together, DeltaNT
      pro-BNP2/1 predicted peak oxygen consumption (B=37.40, r=0.38, p=0.007); cortisol
      at 3 predicted heart rate increase between 2 and 3 (r=-0.38,B=-0.06, p=0.005);
      cortisol at 2 predicted peak carbon-dioxide output (B=2.27, r=0.35, p<0.001);
      DeltaACTH3/2 predicted peak ventilatory equivalent for carbon-dioxide (B=0.03,
      r=0.33, p=0.003). The relation of cortisol at 1 with NT-pro-BNP at 1 and 3 was
      demonstrated using logistic function in all the participants together (for
      1/cortisol at 1 B=63.40, 58.52; r=0.41, 0.34; p=0.003, 0.013, respectively).
      DeltaNT-pro-BNP2/1 linearly correlated with DeltaACTH4/3 in WP and W (r=-0.45, 
      0.48; p=0.04, 0.04, respectively). These results demonstrate for the first time
      that HPA axis and NT-pro-BNP interface in physical stress probably contribute to
      integrative regulation of cardiopulmonary performance. 

PMID- 23876604
TI  - Isolation and identification of antioxidant peptides derived from whey protein
      enzymatic hydrolysate by consecutive chromatography and Q-TOF MS.
AB  - To isolate and identify antioxidant peptides from enzymatically hydrolysed whey
      protein, whey protein isolate was hydrolysed by different protease (trypsin,
      pepsin, alcalase 2.4L, promatex, flavourzyme, protease N). The hydrolysate
      generated by alcalase 2.4L had the highest antioxidant activities on 1,1-diphenyl
      2-picrylhydrazyl (DPPH) radicals, superoxide radicals and in a linoleic acid
      peroxidation system induced by Fe2+. The IC50 values of DPPH and superoxide
      radical scavenging activities of the hydrolysate decreased significantly (6.89
      and 38.88%, respectively) after treatment with macroporous adsorption resin.
      Seven different peptides showing strong antioxidant activities were isolated from
      the hydrolysate using consecutive chromatographic methods including gel
      filtration chromatography and high-performance liquid chromatography. The
      molecular mass and amino acids sequences of the purified peptides were determined
      using a Quadrupole time-of-flight mass spectrometer (Q-TOF MS). One of the
      antioxidative peptides, Trp-Tyr-Ser-Leu, displayed the highest DPPH radical
      scavenging activity (IC50=273.63 MUm) and superoxide radical scavenging activity
      (IC50=558.42 MUm). These results suggest that hydrolysates from whey proteins are
      good potential source of natural antioxidants. 

PMID- 23876605
TI  - Use of whey permeate containing in situ synthesised galacto-oligosaccharides for
      the growth and preservation of Lactobacillus plantarum.
AB  - Galacto-oligosaccharides (GOS) are prebiotics that have a beneficial effect on
      human health by promoting the growth of probiotic bacteria in the gut. GOS are
      commonly produced from lactose in an enzymatic reaction catalysed by beta
      galactosidase, named transglycosylation. Lactose is the main constituent of whey
      permeate (WP), normally wasted output from the cheese industry. Therefore, the
      main goal of this work was to optimise the synthesis of GOS in WP using beta
      galatosidase from Aspergillus oryzaea. WP and whey permeate enzymatically treated
      (WP-GOS) were used as culture media of Lactobacillus plantarum 299v. Lb.
      plantarum 299v attained the stationary phase in approximately 16 h, reaching 3.6
      and 4.1*108 CFU/ml in WP and WP-GOS, respectively. The in situ synthesised GOS
      were not consumed during growth. No significant differences were observed in the
      growth kinetics of microorganisms in both media. After fermentation,
      microorganisms were dehydrated by freeze-drying and spray-drying and stored. The
      recovery of microorganisms after fermentation, dehydration and storage at 4 
      degrees C for at least 120 d was above 108 CFU/g. These studies demonstrated that
      WP is an appropriate substrate for the synthesis of GOS and the obtained product
      is also adequate as culture medium of Lb. plantarum 299v. The coexistence of GOS
      and dehydrated viable probiotic microorganisms, prepared using an effluent as raw
      material, represents the main achievement of this work, with potential impact in
      the development of functional foods. 

PMID- 23876606
TI  - BMC preface.

PMID- 23876607
TI  - Risk of glove perforation with arthroscopic knot tying using different surgical
      gloves and high-tensile strength sutures.
AB  - PURPOSE: To examine the risk of glove tears associated with arthroscopic knot
      tying using 4 commonly used high-tensile strength sutures and 2 different types
      of gloves. METHODS: We analyzed 2 different surgical latex glove types (0.24-mm
      thick powder-free and 0.32-mm-thick powdered) for perforation after arthroscopic
      knot tying with 4 different high-tensile strength sutures: Hi-Fi (ConMed
      Linvatec, Largo, FL), Ultrabraid (Smith & Nephew, Memphis, TN), FiberWire
      (Arthrex, Naples, FL), and Orthocord (DePuy Mitek, Raynham, MA). All knots were
      tied by a double-gloved single surgeon. Twelve trials of 4 knots each were
      performed for every glove-suture combination. All gloves were analyzed for
      perforation by a blinded evaluator using visual inspection, hydro-insufflation,
      and electroconductivity. RESULTS: The overall incidence of glove perforation was
      3.4% and was detectable only by the electroconductivity method; the other 2
      methods did not detect any perforations. There was a statistically significantly
      higher rate (P < .001) of perforations in the 0.32-mm powdered gloves (6.8%)
      compared with the 0.24-mm powder-free gloves (0%). Perforation of the inner glove
      occurred 5.7 times more frequently than perforation of the outer glove. However,
      simultaneous perforation of both the inner and outer gloves did not occur in any
      set. The Hi-Fi suture was involved in 6 perforations compared with 4 for
      FiberWire, 3 for Ultrabraid, and 0 for Orthocord. CONCLUSIONS: Double gloving
      provides an adequate surgical barrier between the surgeon and the patient during
      arthroscopic knot tying with high-tensile strength sutures as indicated by the
      low incidence of glove perforations in our study in an in vitro biomechanical
      evaluation. There were no instances of simultaneous perforation of both the inner
      and outer gloves. All perforations occurred only in the thicker (0.32-mm)
      powdered gloves. CLINICAL RELEVANCE: Glove tears and finger lacerations have been
      reported with the use of high-tensile strength sutures during arthroscopic
      shoulder surgery, thereby raising a concern for safety and disease transmission.
      This study addresses these concerns by evaluating the risk of glove tears during
      arthroscopic knot tying.

PMID- 23876608
TI  - Preliminary results of a novel single-stage cartilage restoration technique:
      particulated juvenile articular cartilage allograft for chondral defects of the
      patella.
AB  - PURPOSE: To evaluate outcomes and magnetic resonance imaging (MRI) findings after
      use of particulated juvenile cartilage for the treatment of focal Outerbridge
      grade 4 articular cartilage defects of the patella. METHODS: From 2007 to 2011,
      16 patients (2 bilateral) underwent a novel single-stage articular cartilage
      restoration procedure using particulated juvenile articular cartilage allograft.
      We enrolled 15 knees (13 patients) in this study. The mean age at surgery was
      26.4 +/- 9.1 years, and the mean postoperative follow-up was 28.8 +/- 10.2
      months. A musculoskeletal radiologist evaluated each knee with postoperative MRI
      for the International Cartilage Repair Society cartilage repair assessment score,
      graft hypertrophy, bony changes around the graft, and percent fill of the defect.
      All patients also completed the Knee Injury and Osteoarthritis Outcome Score,
      International Knee Documentation Committee Subjective Knee Evaluation, and Kujala
      clinical outcome survey (scale, 0 to 100), as well as the Tegner activity scale
      and visual analog pain scale (scale, 0 to 10). RESULTS: The mean International
      Cartilage Repair Society cartilage repair assessment score on MRI was 8.0 +/-
      2.8, a nearly normal assessment. Of 15 knees, 11 (73%) were found to have normal
      or nearly normal cartilage repair. Three patients had mild graft hypertrophy
      whereas 2 had gross graft hypertrophy, 2 of whom required arthroscopic
      debridement because of symptoms. The mean fill of the defect at follow-up was 89%
      +/- 19.6%, with 12 of 15 knees (80%) showing at least 90% defect coverage. The
      mean clinical outcome score at follow-up was 73.3 +/- 17.6 for the International
      Knee Documentation Committee evaluation, and the mean scores for each subdomain
      of the Knee Injury and Osteoarthritis Outcome Score were as follows: 84.2 +/-
      14.2 for pain, 85.0 +/- 12.3 for symptoms and stiffness, 88.9 +/- 12.9 for
      activities of daily living, 62.0 +/- 25.1 for sports and recreation, and 60.8 +/-
      28.6 for quality of life. The median score for the Kujala survey was 79 (range,
      55 to 99). The median score on the Tegner activity scale was 5 (range, 3 to 9),
      and the mean score on the visual analog scale was 1.9 +/- 1.4, indicating minimal
      pain. CONCLUSIONS: Preliminary results suggest that cartilage restoration using
      particulated juvenile articular cartilage allograft offers a viable option for
      patients with focal grade 4 articular cartilage defects of the patella.

PMID- 23876609
TI  - The evolution of suture anchors in arthroscopic rotator cuff repair.
AB  - The advancement of suture anchor design and technology has fostered the
      transition from open to arthroscopic rotator cuff repair. Current suture-bridging
      constructs have greatly surpassed the biomechanical strength parameters of
      transosseous repairs and have shown impressive healing rates after arthroscopic
      rotator cuff repair. This review describes this evolution and discusses the
      important characteristics of suture anchors. 

PMID- 23876610
TI  - Silent, generic and plant kairomone sensitive odorant receptors from the Southern
      house mosquito.
AB  - The Southern house mosquito Culex quinquefasciatus has the largest repertoire of
      odorant receptors (ORs) of all mosquitoes and dipteran species whose genomes have
      been sequenced to date. Previously, we have identified and de-orphanized two ORs
      expressed in female antennae, CquiOR2 and CquiOR10, which are sensitive to
      oviposition attractants. In view of a new nomenclature for the Culex genome
      (VectorBase) we renamed these ORs as CquiOR21 (formerly CquiOR10) and CquiOR121
      (CquiOR2). In addition, we selected ORs from six different phylogenetic groups
      for deorphanization. We cloned four of them by using cDNA from female antennae as
      a template. Attempts to clone CquiOR87 and CquiOR110 were unsuccessful either
      because they are pseudogenes or are not expressed in adult female antennae, the
      main olfactory tissue. By contrast, CquiOR1, CquiOR44, CquiOR73, and CquiOR161
      were highly expressed in female antennae. To de-orphanize these ORs, we employed
      the Xenopus oocyte recording system. CquiORx-CquiOrco-expressed oocytes were
      challenged with a panel of 90 compounds, including known oviposition attractants,
      human and vertebrate host odorants, plant kairomones, and naturally occurring
      repellents. While CquiOR161 did not respond to any test compound in two different
      laboratories, CquiOR1 showed the features of a generic OR, with strong responses
      to 1-octen-3-ol and other ligands. CquiOR44 and CquiOR73 showed preference to
      plant-derived terpenoids and phenolic compounds, respectively. While fenchone was
      the best ligand for the former, 3,5-dimethylphenol elicited the strongest
      responses in the latter. The newly de-orphanized ORs may be involved in reception
      of plant kairomones and/or natural repellents. 

PMID- 23876611
TI  - How life changes itself: the Read-Write (RW) genome.
AB  - The genome has traditionally been treated as a Read-Only Memory (ROM) subject to
      change by copying errors and accidents. In this review, I propose that we need to
      change that perspective and understand the genome as an intricately formatted
      Read-Write (RW) data storage system constantly subject to cellular modifications
      and inscriptions. Cells operate under changing conditions and are continually
      modifying themselves by genome inscriptions. These inscriptions occur over three
      distinct time-scales (cell reproduction, multicellular development and
      evolutionary change) and involve a variety of different processes at each time
      scale (forming nucleoprotein complexes, epigenetic formatting and changes in DNA
      sequence structure). Research dating back to the 1930s has shown that genetic
      change is the result of cell-mediated processes, not simply accidents or damage
      to the DNA. This cell-active view of genome change applies to all scales of DNA
      sequence variation, from point mutations to large-scale genome rearrangements and
      whole genome duplications (WGDs). This conceptual change to active cell
      inscriptions controlling RW genome functions has profound implications for all
      areas of the life sciences. 

PMID- 23876613
TI  - [Benefits and disadvantages of telemedicine].
AB  - Telemedicine is used more and more frequently worldwide. It is increasingly
      popular in North America, Australia, South Africa, as well as the Scandinavian
      countries. However, it is not commonly used in Hungary despite various attempts,
      which is presumably due to earlier dismissive governmental attitude. In this
      paper the authors analyze ethical, legal and financial aspects of telemedicine
      from the viewpoints of physicians and patients, too. The results indicate that it
      cannot be clearly decided whether telemedicine is worth to apply at present.
      Further, introduction of telemedicine should be based on experience gained in
      local application.

PMID- 23876614
TI  - [Orthopaedic relevance of baby carrying].
AB  - Recently, various ways of carrying a baby have become popular again. Different
      methods and options of infant carrying are largely influenced by current fashion
      trends. The term of baby carrying refers to carrying the infant close to the
      caregiver's body with special devices, which aid attachment parenting. The
      authors often face the question in the pediatric orthopedic clinic: what kind of
      carrying method to recommend to the parents. In this article the authors briefly
      present the different means of carrying devices and they review the literature
      regarding orthopedic consequences of baby carrying. For the healthy development
      of a child, position and correct support of the hips and the spine are essential,
      whereas the carrier's spinal protection is also an important aspect. After
      reviewing the literature, the authors conclude that baby carrying with an
      adequate device has advantages from orthopaedic point of view.

PMID- 23876612
TI  - Duration of immunity to norovirus gastroenteritis.
AB  - The duration of immunity to norovirus (NoV) gastroenteritis has been believed to
      be from 6 months to 2 years. However, several observations are inconsistent with
      this short period. To gain better estimates of the duration of immunity to NoV,
      we developed a mathematical model of community NoV transmission. The model was
      parameterized from the literature and also fit to age-specific incidence data
      from England and Wales by using maximum likelihood. We developed several
      scenarios to determine the effect of unknowns regarding transmission and immunity
      on estimates of the duration of immunity. In the various models, duration of
      immunity to NoV gastroenteritis was estimated at 4.1 (95% CI 3.2-5.1) to 8.7 (95%
      CI 6.8-11.3) years. Moreover, we calculated that children (<5 years) are much
      more infectious than older children and adults. If a vaccine can achieve
      protection for duration of natural immunity indicated by our results, its
      potential health and economic benefits could be substantial. 

PMID- 23876615
TI  - [Transmethylation and the redox homeostasis].
AB  - INTRODUCTION: Transmethylation modifies configuration and proceeds via
      formaldehyde. It has a significant role for example in epigenetic regulation. The
      whole methyl-pool can be evaluated by the measurement of bound formaldehyde. AIM:
      The bound formaldehyde was measured in wheat, bean, beetroot, cabbage, broiler-
      and rabbit liver. The relationship between transmethylation and redox
      homeosthasis was studied in the liver of domestic animals, and in the rat model
      of fatty liver. METHOD: The diet of rats was enriched with cholesterol, sunflower
      oil and cholic acid. The bound formaldehyde was determined by overpressured layer
      chromatography. The hydrogen-donating ability was measured with 1.1-diphenyl-2
      picrylhydrazylt free radical using spectrophotometric measurement. RESULTS: Beans
      had the most bound formaldehyde. The liver of broilers possessed significantly
      elevated hydrogen-donating ability and transmethylation ability. Rats with severe
      fatty liver had significantly less bound formaldehyde and the hydrogen-donating
      ability tendentiously decreased. CONCLUSIONS: These results draw attention to the
      diet, especially in obesity and obesity-related diseases.

PMID- 23876616
TI  - [Clostridium difficile infection: epidemiology, disease burden and therapy].
AB  - INTRODUCTION: C. difficile causes 25 percent of the antibiotic associated
      infectious nosocomial diarrhoeas. C. difficile infection is a high-priority
      problem of public health in each country. The available literature of C.
      difficile infection's epidemiology and disease burden is limited. AIM: Review of
      the epidemiology, including seasonality and the risk of recurrences, of the
      disease burden and of the therapy of C. difficile infection. METHOD: Review of
      the international and Hungarian literature in MEDLINE database using PubMed up to
      and including 20th of March, 2012. RESULTS: The incidence of nosocomial C.
      difficile associated diarrhoea is 4.1/10 000 patient day. The seasonality of C.
      difficile infection is unproved. 20 percent of the patients have recurrence after
      metronidazole or vancomycin treatment, and each recurrence increases the chance
      of a further one. The cost of C. difficile infection is between 130 and 500
      thousand HUF (430 ? and 1665 ?) in Hungary. CONCLUSIONS: The importance of C.
      difficile infection in public health and the associated disease burden are
      significant. The available data in Hungary are limited, further studies in
      epidemiology and health economics are required.

PMID- 23876617
TI  - [Hungarian medical history in Kosice/Kassa, a European Capital of Culture].

PMID- 23876618
TI  - [To the Editors: HPV vaccination].

PMID- 23876619
TI  - Understanding lead dysfunction: managing lead failure grief.

PMID- 23876620
TI  - Phylogeny as the basis for naming histones.

PMID- 23876622
TI  - Properties of commonly used calcium phosphate cements in trauma and orthopaedic
      surgery.

PMID- 23876623
TI  - Clavicle and coracoid process drilling technique for truly anatomic
      coracoclavicular ligament reconstruction.
AB  - BACKGROUND: High-grade acromioclavicular (AC) joint separations require surgical
      treatment, as conservative treatment may result in functional decline or
      persistent pain. Although many surgical techniques have been described in the
      literature, there is still no non-controversial gold standard procedure for AC
      joint dislocation. The different orientation of the two components of the
      coracoclavicular (CC) ligaments has been proven to account for different
      functions. However, the majority of the techniques reconstruct the CC ligaments
      with a single structure. The purposes of this study were to assess the
      feasibility of truly anatomic coracoclavicular ligament reconstruction (TACCR)
      and to determine the corresponding drilling parameter. METHODS: We constructed
      virtual three-dimensional (3D) models of 105 shoulders from computed tomography
      (CT) scan data by using SuperImage software. For each model, the attachment sites
      and footprint dimensions of the conoid and trapezoid ligaments were defined and
      adjusted according to previously defined anatomic parameters and individual
      measurement results. Virtual drilling and 3D measurement were carried out in each
      model separately. Guided by the drilling parameter, we performed TACCR on 24
      shoulders from 12 whole cadavers after transecting the AC and CC ligaments.
      RESULTS: The collinear drilling technique was noted to breach the bone cortex of
      the clavicle and/or the coracoid process in 95 of 105 virtual models (90.5%). No
      cortical breach was observed using a non-collinear drilling technique. The
      anteversion angulation of the conoid-coracoid tunnel ranged from 10 degrees  to
      15 degrees  (mean value 12.4 degrees ). The extraversion angulation of the conoid
      coracoid tunnel varied from 5 degrees  to 10 degrees  (mean value 6.8 degrees ).
      The anteversion angulation of the trapezoid-coracoid tunnel ranged from 20
      degrees  to 30 degrees  (mean value 25.2 degrees ). There were no failures when
      performing the non-collinear drilling technique on cadaver models. CONCLUSIONS:
      The collinear drilling technique is not technically feasible for TACCR. For this
      reason, we recommend the non-collinear drilling technique, which provides the
      ability to prepare bony tunnels without any risk of cortical breach. CLINICAL
      RELEVANCE: Based on this computer and cadaver model study, we have devised a
      novel drilling technique to restore the CC ligaments anatomically.

PMID- 23876621
TI  - Telomerase at the intersection of cancer and aging.
AB  - Although cancer and aging have been studied as independent diseases, mounting
      evidence suggests that cancer is an aging-associated disease and that cancer and
      aging share many molecular pathways. In particular, recent studies validated
      telomerase activation as a potential therapeutic target for age-related diseases;
      in addition, abnormal telomerase expression and telomerase mutations have been
      associated with many different types of human tumor. Here, we revisit the
      connection between telomerase and cancer and aging in light of recent findings
      supporting a role for telomerase not only in telomere elongation, but also in
      metabolic fitness and Wnt activation. Understanding the physiological impact of
      telomerase regulation is fundamental given the therapeutic strategies that are
      being developed that involve telomerase modulation. 

PMID- 23876625
TI  - Transosseous suturing of patellar fractures with braided polyester - a
      prospective cohort with a matched historical control study.
AB  - BACKGROUND: Although tension-band wiring is the most widely used technique to fix
      patellar fractures, metal implant-related complications including implant failure
      and postoperative pain are very common and additional procedures are often
      necessary to treat the complications. The purpose of this study is to evaluate a
      totally metal-free technique using a transosseous suturing method and to compare
      it with the traditional fixation technique. METHOD: A total of 25 patients (mean
      age of 59.60 years) with displaced patellar fractures treated by a transosseous
      suturing technique were compared with a 1:1 matched historical control group that
      underwent modified tension-band-wire fixation. Union time, union rate, operation
      time, number of procedures, mean hospitalisation days and complications were
      compared between cases and controls. RESULTS: Union time (8.43 +/- 2.92 vs. 8.64
      +/- 2.82 weeks) and operation time (69.00 +/- 19.31 vs. 64.89 +/- 14.27 min) were
      not different between the two groups. Mean hospitalisation days (4.04 +/- 1.40
      vs. 5.76 +/- 1.50 days; P<0.001), number of procedures and the frequency of
      complications were significantly lower in the transosseous suturing group.
      CONCLUSION: The transosseous suturing technique is safe and effective in the
      transverse or comminuted fractures of the patella. The complication rate is
      significantly lower than with the tension-band-wiring technique.

PMID- 23876624
TI  - A multicentre, prospective, randomised comparison of the sliding hip screw with
      the Medoff sliding screw and side plate for unstable intertrochanteric hip
      fractures.
AB  - OBJECTIVE: This study aimed to compare the dynamic hip screw (DHS) and Medoff
      sliding plate (MSP) for unstable intertrochanteric hip fractures. DESIGN: A
      randomised, prospective trial design was used. SETTING: The study was undertaken
      in two level-1 trauma centres and one community hospital. PATIENTS/PARTICIPANTS:
      A total of 163 patients with unstable intertrochanteric hip fractures
      (Orthopaedic Trauma Association (OTA) 31-A2) were randomised to DHS or MSP.
      Inclusion and exclusion criteria were designed to focus on isolated unstable
      intertrochanteric hip fractures in ambulatory patients. INTERVENTION:
      Randomisation was performed intra-operatively, after placement of a 135 degrees 
      guide wire. Follow-up assessments were performed at regular intervals for a
      minimum of 6 months. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was
      re-operation rate. The secondary outcome was patient function, evaluated using a
      validated outcome measure, the Hip Fracture Functional Recovery Score. Tertiary
      outcomes included: mortality, hospital stay, quality of reduction and malunion
      rate. RESULTS: A total of 86 patients were randomised to DHS and 77 to MSP. The
      groups had similar patient demographics, pre-fracture status and in-hospital
      course. The quality of reduction was the same for each group, but the operative
      time was longer in the MSP group (61.6 vs. 50.1min, P=0.01). The rate of re
      operation was low (3/86 in DHS and 2/77 in MSP) with no statistically significant
      difference. The functional outcomes were the same for both groups, with
      functional recovery scores at 6 months of 51.0% in the DHS arm and 49.7% in the
      MSP arm. CONCLUSIONS: The two techniques produced similar results for the
      clinically important outcomes of the need for further surgery and functional
      status of the patients at 6 months' follow-up.

PMID- 23876626
TI  - Prospects for prevention of HPV-driven oropharynx cancer.
AB  - Prevention of HPV-associated cancers can take two forms-one through prevention of
      infection via prophylactic HPV vaccination, and one through interruption of
      disease progression through early identification (i.e.: screening) and treatment.
      Primary prevention via vaccination seems promising, as a proof-of-principal study
      demonstrated high vaccine efficacy against one-time detection of oral HPV16/18
      infection. In addition to the direct benefit of vaccination, indirect protection
      from reduced genital HPV infection should also reduce oral HPV exposure at the
      individual level. Yet, for the current unvaccinated cohorts who will bear the
      burden of non-cervical HPV-associated cancers for the foreseeable future, no
      secondary prevention opportunities exist, as the field has not yet validated any
      screening methods for non-cervical HPV associated cancers. Serum HPV16 E6
      antibody data suggest that this test might one day be able to detect many of the
      at-risk patients prior to tumor development. For any biomarker that proves valid
      and reliable, transitioning into clinical practice will require additional
      research focused on (1) diagnostics, (2) effective intervention, and (3) observed
      reductions in cancer mortality. 

PMID- 23876628
TI  - Relevance of cancer initiating/stem cells in carcinogenesis and therapy
      resistance in oral cancer.
AB  - Oral squamous cell carcinoma (OSCC) acquires the top most position among the
      other malignancies and patients die with this disease complication within 5years.
      One of the causes behind this scenario is the identified sub-population in
      heterogeneous tumor mass that are purported as cancer stem cells (CSCs) or tumor
      initiating cells (TICs). Oral CSCs populations show upregulation of the stem cell
      related genes Oct-4, Nanog, Nestin, CK19, BMI-1, CD117 (c-kit), CD44 and CD133
      with sunken expression of involucrin and CK13. This small proportion of tumor
      cells can sustain tumor growth, proliferation, invasion and distant metastasis
      playing a pivotal role in relapse of oral cancer. Unanimous risk factors include
      prevalent use of cigarette smoking, tobacco chewing with less explored HPV
      infection play an important role in origin of CSCs. Moreover, highly apoptotic
      resistant oral CSCs show enhanced protective autophagy for survival. Several
      studies report them to be more chemo and radiation resistant than non-stem cell
      population implicating the failure of the present cancer therapy. This resistance
      associated with normal stem cell protective mechanisms including increased
      expression of drug efflux pumps, alteration in program cell death, cell cycle,
      and DNA repair mechanisms. Notably, CSCs appear to play a major role in tumor
      recurrence and metastatic spread, common causes of the high morbidity and
      ultimately the death of the majority of patients with oral cancer. In this review
      we would like to highlight the intricate crosstalk of the cancer initiating/stem
      cells involved in carcinogenesis and potential hurdle to oral cancer therapy. 

PMID- 23876627
TI  - Discussing the diagnosis of HPV-OSCC: common questions and answers.
AB  - Human papillomavirus (HPV) is responsible for a rising proportion of
      oropharyngeal squamous cell cancers (OSCCs). HPV-positive OSCCs (HPV-OSCCs) are
      associated with oral HPV infection and sexual behavior. Patient questions
      regarding risk factors, prognosis and implications for past, present and future
      relationships often arise. This manuscript addresses frequently asked questions
      by patients with HPV-OSCC and their families. A framework for clinicians to
      address these conversations and the limitations of our present knowledge base is
      also presented. 

PMID- 23876629
TI  - Age and nutritional state influence the effects of cholecystokinin on energy
      balance.
AB  - Cholecystokinin (CCK) is anorexic, irrespective whether it is applied
      intraperitoneally (IP) or intracerebroventricularly (ICV) in male Wistar rats.
      The metabolic effects depend on the route of administration: by the IP route it
      elicits hypothermia (presumably by type-1 receptors, CCK1R-s), while ICV
      administration is followed by fever-like hypermetabolism and hyperthermia via
      activation of CCK2R-s, which latter response seems to be most important in the
      postprandial (compensatory) hypermetabolism. The efficacy of the IP injected CCK
      varies with age: it causes strong anorexia in young adult 4 and 6-months old and
      again in old rats (aged 18-24 months), but the middle-aged (12-month old) ones
      seem to be resistant to this effect. Such pattern of effects may contribute to
      the explanation of age-related obesity observed in middle-aged animals as well as
      to the aging anorexia and loss of body weight in old ones. Diet-induced obesity
      accelerates the appearance of CCK-resistance as well as the return of high
      sensitivity to CCK in further aging, while chronic calorie-restriction prevents
      the development of resistance, as if the speed of the age-related regulatory
      changes was altered by the nutritional state. The effects of ICV applied CCK also
      change with age: the characteristic anorexic and hypermetabolic/hyperthermic
      effects can be observed in young adult rats, but the effects gradually and
      monotonically decline with age and disappear by the old age of 24 months. These
      disparate age-related patterns of CCK efficacy upon peripheral or central
      administration routes may indicate that although both peripheral and central CCKR
      s exert anorexic effects, they may have dissimilar roles in the regulation of
      overall energy balance.

PMID- 23876630
TI  - An oversized allograft is associated with improved survival after lung
      transplantation for idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is associated with
      high short-term mortality after bilateral lung transplantation (BLT). Previous
      studies have suggested that oversized allografts are associated with improved
      outcomes and that this association was strongest within the first year after
      transplant. We hypothesized that oversizing the allograft is associated with
      improved survival after BLT for IPAH. METHODS: All adults in the United Network
      of Organ Sharing lung transplant registry who underwent first-time BLT for IPAH
      between October 1989 and April 2010 were studied. Lung size mismatch was assessed
      by calculating the predicted total lung capacity (pTLC) ratio of the donor to the
      recipient. The cohort was divided evenly into "undersized" (pTLC ratio less than
      the median pTLC ratio) and "oversized" (pTLC ratio exceeding the median pTLC
      ratio). Risk of death after BLT was analyzed using Kaplan-Meier survival and Cox
      proportional hazards models. RESULTS: The mean pTLC ratio was 0.93 +/- 0.10 in
      the 302 undersized patients compared with 1.24 +/- 0.14 in the 302 oversized
      patients. Cohorts had comparable baseline characteristics. Median survival was
      831 days longer in the oversized cohort (2,166 vs. 1,335 days, p = 0.006). In a
      multivariate model controlling for sex mismatch, recipient factors, acuity, donor
      factors, and transplant factors, oversizing was associated with decreased hazard
      for death at 5 years (hazard ratio, 0.73; 95% CI 0.56-0.96, p = 0.02).
      CONCLUSION: Oversizing the allograft is associated with improved survival after
      BLT for IPAH. In the setting of donor organ shortages and waiting list mortality,
      it is not practical to intentionally oversize the allograft. However, the pTLC
      ratio could provide further refinement in the peri-transplant risk assessment.

PMID- 23876631
TI  - Neuronal damage and cognitive impairment associated with hypoglycemia: An
      integrated view.
AB  - The aim of the present review is to offer a current perspective about the
      consequences of hypoglycemia and its impact on the diabetic disorder due to the
      increasing incidence of diabetes around the world. The main consequence of
      insulin treatment in type 1 diabetic patients is the occurrence of repetitive
      periods of hypoglycemia and even episodes of severe hypoglycemia leading to coma.
      In the latter, selective neuronal death is observed in brain vulnerable regions
      both in humans and animal models, such as the cortex and the hippocampus.
      Cognitive damage subsequent to hypoglycemic coma has been associated with
      neuronal death in the hippocampus. The mechanisms implicated in selective damage
      are not completely understood but many factors have been identified including
      excitotoxicity, oxidative stress, zinc release, PARP-1 activation and
      mitochondrial dysfunction. Importantly, the diabetic condition aggravates
      neuronal damage and cognitive failure induced by hypoglycemia. In the absence of
      coma prolonged and severe hypoglycemia leads to increased oxidative stress and
      discrete neuronal death mainly in the cerebral cortex. The mechanisms responsible
      for cell damage in this condition are still unknown. Recurrent moderate
      hypoglycemia is far more common in diabetic patients than severe hypoglycemia and
      currently important efforts are being done in order to elucidate the relationship
      between cognitive deficits and recurrent hypoglycemia in diabetics. Human studies
      suggest impaired performance mainly in memory and attention tasks in healthy and
      diabetic individuals under the hypoglycemic condition. Only scarce neuronal death
      has been observed under moderate repetitive hypoglycemia but studies suggest that
      impaired hippocampal synaptic function might be one of the causes of cognitive
      failure. Recent studies have also implicated altered mitochondrial function and
      mitochondrial oxidative stress. 

PMID- 23876632
TI  - Activation of ERK signaling in rostral ventromedial medulla is dependent on
      afferent input from dorsal column pathway and contributes to acetic acid-induced
      visceral nociception.
AB  - Several lines of evidence from both animal and clinical studies have demonstrated
      that dorsal column (DC) pathway plays a critical role in visceral pain
      transmission from the spinal cord to supraspinal center. The descending pain
      modulation pathway from the rostral ventromedial medulla (RVM) area has been
      implicated in visceral nociceptive neurotransmission. Previous studies have
      demonstrated that the multiple protein kinase signaling transduction cascades in
      the RVM area contribute to the descending facilitation of inflammatory pain and
      neuropathic pain. However, whether these signaling transduction pathways in the
      RVM area are triggered by the afferent visceral input from the DC pathway during
      acute visceral pain remains elusive. Here, we have tested the hypothesis that the
      afferent visceral stimuli from the DC pathway might induce the activation of
      extracellular signal-regulated protein kinase (ERK) signaling in the RVM area and
      contribute to the descending facilitation of neurotransmission in a rat model of
      visceral pain. Our results showed that acetic acid-induced visceral nociception
      produced a persistent activation of ERK in the RVM area and a microinjection of a
      mitogen-activated ERK kinase (MEK) inhibitor, U0126, into the RVM area
      significantly inhibited the visceral noxious stimulation-induced behaviors in
      rats. A microinjection of lidocaine into the nucleus gracilis (NG) also inhibited
      the activation of ERK in the RVM area. The current study indicates that activated
      ERK signaling pathway in the RVM area is dependent on afferent input from dorsal
      column pathway and may contribute to acetic acid-induced visceral nociception. 

PMID- 23876633
TI  - Antenatal diagnosis of dacryocystocele.

PMID- 23876634
TI  - Exercise and reproduction.

PMID- 23876635
TI  - Aboriginal maternity care resourcebook.

PMID- 23876636
TI  - Perspectives of family physicians on the care of uninsured pregnant women.
AB  - OBJECTIVE: No official provisions are made for the medically uninsured under
      provincial public health programs in Canada. Studies have shown that uninsured
      pregnant women have inadequate access to prenatal and obstetrical services that
      favour healthy maternal and child outcomes. This qualitative study aimed to
      explore the perspectives of family physicians who provided care to uninsured
      pregnant women. METHODS: Eight family physicians affiliated with two Montreal
      based primary-care clinics and one tertiary care hospital between 2004 and 2007
      were interviewed using a semi-structured interview guide. Data were assessed
      using thematic analysis. RESULTS: Uninsured pregnant patients were characterized
      by physicians as socially vulnerable, with precarious immigration status that
      limited their access to health services. Uninsured patients were thought not to
      benefit from the same standard of perinatal care as their insured counterparts.
      Care of uninsured women was generally thought to be a professional obligation,
      regardless of the woman's ability to pay. Caring for this population was
      considered by family physicians to be challenging, engendering psychological
      stress, increased workload, and occasional tensions with other health care
      providers. CONCLUSION: In the present context, family physicians are left to
      negotiate the health care system in an attempt to provide adequate perinatal care
      for uninsured pregnant patients. This situation has repercussions for physicians,
      for patients and, ultimately, for infants. Leadership is required to ensure that
      all pregnant women in Canada have access to appropriate health care during the
      perinatal period.

PMID- 23876637
TI  - Maternal and perinatal outcomes of extreme obesity in pregnancy.
AB  - OBJECTIVE: To evaluate the effects of extreme obesity (pre-pregnancy BMI >= 50.0
      kg/m2) in pregnancy on maternal and perinatal outcomes. METHODS: We conducted a
      population-based cohort study using the Newfoundland and Labrador Perinatal
      Database to compare obstetric outcomes in women with extreme obesity and those
      with a normal BMI (pre-pregnancy BMI 18.50 to 24.99 kg/m2). We included women
      with singleton gestations who gave birth between January 1, 2002, and December
      31, 2011. Maternal outcomes of interest included gestational hypertension,
      gestational diabetes, Caesarean section, shoulder dystocia, length of hospital
      stay, maternal ICU admission, postpartum hemorrhage, and death. Perinatal
      outcomes included birth weight, preterm birth, Apgar score, neonatal metabolic
      abnormality, NICU admission, stillbirth, and neonatal death. A composite
      morbidity outcome was developed including at least one of Caesarean section,
      gestational hypertension, birth weight >= 4000 g, birth weight < 2500 g, or NICU
      admission. Univariate analyses and multivariate logistic regression analyses
      (controlling for maternal age, parity, smoking, partner status, and gestational
      age) were performed, and adjusted odds ratios (aORs) and 95% confidence intervals
      were calculated. RESULTS: A total of 5788 women were included in the study: 71
      with extreme obesity and 5717 with a normal BMI. Extremely obese women were more
      likely to have gestational hypertension (19.7% vs. 4.8%) (aOR 1.56; 95% CI 1.33
      to 1.82), gestational diabetes (21.1% vs. 1.5%) (aOR 2.04; 95% CI 1.74 to 2.38),
      shoulder dystocia (7.1% vs. 1.4%) (aOR 1.51; 95% CI 1.05 to 2.19), Caesarean
      section (60.6% vs. 25.0%) (aOR 1.46; 95% CI 1.29 to 1.65), length of hospital
      stay more than five days (excluding Caesarean section) (14.3% vs. 4.7%) (aOR
      1.42; 95% CI 1.07 to 1.89), birth weight >= 4000 g (38.0% vs. 11.9%) (aOR 1.58;
      95% CI 1.38 to 1.80), birth weight >= 4500 g (16.9% vs. 2.1%) (aOR 1.87; 95% CI
      1.57 to 2.23), neonatal metabolic abnormality (8.5% vs. 2.0%) (aOR 1.50; 95% CI
      1.20 to 1.86), NICU admission (16.9% vs. 7.8%) (aOR 1.28; 95% CI 1.07 to 1.52),
      stillbirth (1.4% vs. 0.2%) (aOR 1.68; 95% CI 1.00 to 2.82) and composite adverse
      outcome (81.7% vs. 41.5%) (aOR 1.57; 95% CI 1.35 to 1.83). CONCLUSION: Women with
      extreme obesity have increased risks of a variety of adverse maternal and
      perinatal outcomes. As approximately 6 per 1000 women giving birth in our
      population have extreme obesity, it is important to address these risks pre
      conceptually and encourage a healthier BMI before pregnancy.

PMID- 23876638
TI  - Maternal mortality and its correlates: practical implications of data analysis
      across multiple countries.
AB  - OBJECTIVE: Studies of maternal mortality that use data from multiple countries
      often identify statistically significant correlates and interpret them as factors
      relevant to policy. This study was designed to address the fragility of a
      statistical association between the maternal mortality rate and its main
      correlates, and to assess the relevance of multi-country data analysis for policy
      making. METHODS: Patterns of variation in the maternal mortality rate associated
      with the fertility rate, income per capita, primary and secondary school
      enrollment, institutional quality, women's participation in politics, and health
      systems indicators across 111 countries in 2000 and 128 countries in 2005 were
      investigated using a linear multilevel modelling approach. RESULTS: The fertility
      rate and income per capita were the only robust predictors of the maternal
      mortality rate. Health systems indicators and school enrollment, after
      controlling for the effect of the fertility rate, income per capita, and region
      specific contextual factors, were found to be unstable direct predictors of the
      maternal mortality rate. CONCLUSION: Although multi-country comparative studies
      can identify key correlates of the maternal mortality rate, policy
      recommendations to reduce maternal mortality should be based on causal models
      that take contextual factors into account.

PMID- 23876639
TI  - Cervical cancer incidence trends in Canada: a 30-year population-based analysis.
AB  - OBJECTIVES: To use the most recent data to update the trend in cervical cancer
      incidence in Canada over the 30 year period from 1978 to 2009. METHODS:
      Registered cases of cervical cancer and the corresponding person years for the
      Canadian population were retrieved from an online data repository of the
      International Agency on Research on Cancer and from Statistics Canada for the
      period 1978 to 2009. Annual age-standardized rates were estimated for all data
      combined and for each province separately. The ages of cases were aggregated into
      three groups: 25 to 39, 40 to 59, and 60 to 75 years. Joinpoint regression
      analysis was used to describe the trend across age groups and provinces. RESULTS:
      Between 1978 and 2006, the age-adjusted cervical cancer rate in Canada decreased
      from 20.05 to 12.66 per 100 000 females; after 2006 the rate increased. Greater
      reductions were observed in the older age groups. The average annual percentage
      change (AAPC) was -1.1% (95% CI -1.1% to 0.09%), -1.8% (95% CI -2.5% to -1.2%),
      and -2.6% (95% CI -3.9% to -1.4%) for age groups 25 to 39, 40 to 60, and 60 to
      75, respectively. The AAPC varied between provinces, ranging from -0.22% (95% CI 
      1.4% to 0.9%) in Saskatchewan to -3.02% (95% CI -4.5% to -1.5%) in Newfoundland
      and Labrador. In Ontario the incidence of cervical cancer increased annually
      between 2006 and 2009. The trend in British Columbia included a significant
      change of slope in 1984. CONCLUSION: The incidence of cervical cancer decreased
      in Canada and across all provinces between 1978 and 2009. The decrease was
      greater in older women.

PMID- 23876640
TI  - Risk-reducing salpingectomy in Canada: a survey of obstetrician-gynaecologists.
AB  - OBJECTIVE: Performing risk-reducing salpingectomy (RRS) at the time of
      hysterectomy or as a method of tubal ligation has been suggested as a way to
      reduce the incidence of high grade serous carcinoma (HGSC) of the ovary, since
      this type of cancer is hypothesized to originate in the fallopian tube. We
      conducted a survey of Canadian obstetrician-gynaecologists to better understand
      the uptake and knowledge of implementing this procedure, and to identify barriers
      to doing so. METHODS: An anonymous, web-based survey using both quantitative and
      qualitative methods was sent to obstetrician-gynaecologist members of the Society
      of Obstetricians and Gynaecologists of Canada and the Society of Gynecologic
      Oncology of Canada. The survey contained questions about demographics, knowledge
      and beliefs about RRS, and possible barriers to its implementation in women at
      average risk for ovarian cancer. RESULTS: One hundred ninety-two physicians
      responded to the survey, a response rate of 25%. Respondents varied in their
      duration in practice, came from all provinces, and spent a large proportion of
      their time practising gynaecology. Ninety percent of respondents had heard of
      RRS; however, 37% were unaware of the evidence supporting the hypothesis that
      HGSC originates in the fallopian tube, and 38% were unsure whether there would be
      any population benefit from performing RRS at the time of other gynaecologic
      surgery. Multiple barriers to implementation were identified. CONCLUSION: Most
      Canadian obstetrician-gynaecologists responding to our survey were aware of RRS
      as a possible method to prevent ovarian cancer in women at average risk; however,
      barriers still exist to widespread implementation. Further research is needed to
      quantify the population benefit of this procedure.

PMID- 23876641
TI  - Preoperative radiotherapy for inoperable stage II endometrial cancer: insights
      into improving treatment and outcomes.
AB  - OBJECTIVE: To review recurrence patterns and survival outcomes of women receiving
      preoperative radiotherapy for clinical stage II endometrial cancer in British
      Columbia. METHODS: We performed a retrospective population-based cohort study of
      all patients with clinical stage II endometrial cancer who were referred to the
      British Columbia Cancer Agency from 2000 to 2008, deemed ineligible for primary
      surgery, and therefore offered preoperative radiotherapy followed by surgery.
      Patient demographics, uterine risk factors, timing and details of treatments, and
      timing and sites of recurrence were obtained from patient records. Primary
      outcome measures were the sites and rates of recurrence and recurrence-free
      survival. RESULTS: We identified 29 patients with a mean age of 61 years (range
      41 to 83) and median follow-up of 3.1 years (range 0.3 to 5.3). Three-year
      overall survival was 79%, and median recurrence-free survival was 2.5 years.
      Eight patients had recurrence of disease (27.6%), with a median time to
      recurrence of 1.3 years, (range 0.4 to 2.7). Six of these eight women had two or
      more high-risk uterine factors (deep myometrial invasion, grade 3 tumour),
      ovarian involvement, or adverse histological type (carcinosarcoma), compared with
      only one of 21 patients without recurrence. Seven of eight women had recurrence
      outside the radiated volume of tissue. Median survival after recurrence was 1.0
      years (range 0.4 to 2.2). CONCLUSIONS: Women with clinical stage II endometrial
      cancer had a significant risk of recurrence when treated with preoperative
      radiotherapy followed by surgery. They were more likely to have distant
      recurrences, implying the need for an alternate treatment paradigm.

PMID- 23876642
TI  - Managing expectations of surgical training: a national perspective on
      gynaecologic endoscopy practice.
AB  - OBJECTIVE: To determine if the opinion of obstetrics and gynaecology postgraduate
      trainees differs from practising gynaecologists with respect to the expected
      endoscopic surgical skill set of a general gynaecologist upon graduation from
      residency. METHODS: An electronic survey was designed, validated, and pre-tested.
      It was sent to 775 Canadian obstetrics and gynaecology residents, fellows, and
      practising physicians through the Society of Obstetricians and Gynaecologists of
      Canada's electronic mailing list. Survey respondents were asked their opinion on
      the level of training (no extra post-residency training vs. fellowship) required
      to perform various endoscopic procedures. RESULTS: We received 301 responses (39%
      response rate). Obstetrics and gynaecology trainees and practising physicians
      agreed on the training and skill level necessary to perform many endoscopic
      procedures. However, there were significant differences of opinion among trainees
      and practising physicians regarding advanced endoscopic procedures such as
      laparoscopic hysterectomy, cystotomy and enterotomy repair, and appendectomy.
      More trainees felt that a general gynaecologist without additional post-residency
      surgical training should be competent to perform such procedures, while
      practising physicians felt fellowship training was necessary. CONCLUSION: Our
      survey highlights the different expectations of learners versus those in practice
      with regard to skills required to perform certain endoscopic procedures,
      particularly laparoscopic hysterectomy. Trainees who responded believed that
      after graduation from residency any obstetrician-gynaecologist should be able to
      perform more advanced endoscopic procedures, but practising physicians did not
      agree. This discordance between learners and practising colleagues highlights an
      important educational challenge in obstetrics and gynaecology surgical training.
      Greater clarification of what is expected of our training programs would be
      beneficial for both residents and training programs.

PMID- 23876643
TI  - A Canadian survey of postgraduate education in Aboriginal women's health in
      obstetrics and gynaecology.
AB  - OBJECTIVE: To assess Canadian obstetrics and gynaecology residents' knowledge of
      and experience in Indigenous women's health (IWH), including a self-assessment of
      competency, and to assess the ability of residency program directors to provide a
      curriculum in IWH and to assess the resources available to support this
      initiative. METHODS: Surveys for residents and for program directors were
      distributed to all accredited obstetrics and gynaecology residency programs in
      Canada. The resident survey consisted of 20 multiple choice questions in four key
      areas: general knowledge regarding Indigenous peoples in Canada; the impact of
      the residential school system; clinical experience in IWH; and a self-assessment
      of competency in IWH. The program director survey included an assessment of the
      content of the curriculum in IWH and of the resources available to support this
      curriculum. RESULTS: Residents have little background knowledge of IWH and the
      determinants of health, and are aware of their knowledge gap. Residents are
      interested in IWH and recognize the importance of IWH training for their future
      practice. Program directors support the development of an IWH curriculum, but
      they lack the resources to provide a comprehensive IWH curriculum and would
      benefit from having a standardized curriculum available. CONCLUSION: A nationwide
      curriculum initiative may be an effective way to facilitate the provision of
      education in IWH while decreasing the need for resources in individual programs.

PMID- 23876644
TI  - The devil we know: the implications of bill C-38 for assisted human reproduction
      in Canada.
AB  - In June 2012, the Canadian House of Commons passed the so-called omnibus budget
      bill, making several important changes to the governance of assisted reproduction
      in Canada. The bill (Bill C-38) was widely criticized for its unwieldy size and
      rapid passage through Parliament, preventing adequate parliamentary debate and
      public scrutiny. Given the substantive nature of the amendments to the Assisted
      Human Reproduction Act made by Bill C-38, and the lack of relevant discussion
      about these changes both before and following its passage, this commentary is
      intended to identify how Bill C-38 may alter the governance of reproductive
      technologies in Canada. In this commentary, we address some of the more
      significant changes made by Bill C-38 to the regulation of reproductive medicine
      in Canada. We identify the benefits and challenges of closing Assisted Human
      Reproduction Canada, noting that doing so eliminates a much-needed forum for
      stakeholder consultation in this field. Further, we explore the implications of
      moving the regulation of donor semen from the Food and Drugs Act to the Assisted
      Human Reproduction Act; these include increased liability for physicians, and
      opportunities to expand the existing regulations to account for the needs of
      lesbian, gay, bisexual, trans, and queer Canadians using donor gametes and recent
      advances in reproductive technologies. Overall, we argue that although the
      implementation of a policy framework in this field remains highly dependent on
      yet-to-be written regulations, the changes to the Assisted Human Reproduction Act
      enabled by Bill C-38 may significantly alter how Canadians interact with
      reproductive technologies. 

PMID- 23876645
TI  - Exploring colposcopists' attitudes towards use of HPV testing as a primary
      screening tool for cervical cancer in British Columbia.
AB  - OBJECTIVE: To examine colposcopists' attitudes regarding human papillomavirus
      (HPV) DNA testing as a primary screening tool for cervical cancer. METHODS:
      Questionnaires administered in 2010 and 2011 during workshops in British Columbia
      elicited colposcopists' attitudes using a series of five-point Likert-style
      scales (strongly disagree to strongly agree) and binary (yes/no) response
      questions. The frequency of "agree" or "strongly agree" was used to characterize
      attitudes. Regression analyses examined statistically significant changes in
      attitudes after the 2010 workshop. RESULTS: Responses generally indicated
      positive changes in attitudes toward HPV testing. Statistically significant
      changes after the 2010 workshop were observed for the items relating to strong
      agreement that HPV is a necessary cause of cervical cancer (39% increase; P <
      0.001) and the likelihood of openly advocating for HPV testing (19% increase; P <
      0.04). In 2010, 40% of colposcopists stated that four years between HPV tests is
      too long, and in 2011, 53% did so. CONCLUSION: Colposcopists are viewed as
      opinion leaders and will have a critical role in implementing HPV testing in BC;
      our study obtained responses from 73% (2010) and 84% (2011) of BC-registered
      colposcopists. Colposcopists were in favour of HPV testing for primary screening
      for cervical cancer but did not support an extended interval for HPV testing,
      which suggests future knowledge translation workshops are crucial. We found that
      knowledge translation workshops can be an effective approach for translating
      evidence on screening and screening practices.

PMID- 23876648
TI  - [Antithrombotic medications and childhood stroke].
AB  - Each year, 500 to 1000 children experience a stroke in France. Long-term follow
      up demonstrates persistent neurologic deficit in most of them. Despite the lack
      of studies with high level of evidence, paediatric stroke guidelines are
      regularly updated based on observational data, analogy with recommendation for
      adults, and expert opinion. It is reasonable to initiate anticoagulation during
      the acute phase of cerebral sinovenous thrombosis in children; the duration of
      anticoagulation needs to be individually tailored. It is not yet possible to draw
      any conclusions regarding neonates. Intravenous or intra-arterial thrombolysis
      and mechanical devices have the potential to provide instant and safe
      recanalization under optimal circumstances, but no generalization about their
      efficacy in childhood ischemic stroke can be drawn. Aspirin is effective in
      reducing the risk of recurrence in children with arterial ischemic stroke. There
      is a need to develop new studies with easy for use of antithrombotic drugs, such
      as aspirin or oral direct factor Xa inhibitors. A specific approach for rare
      disease population, which follows guidance for the design and conduct of
      paediatric trials, is required. 

PMID- 23876646
TI  - Technical update on pessary use.
AB  - OBJECTIVE: To review the use, care, and fitting of pessaries. OPTIONS: Pessaries
      are an option for women presenting with prolapse and/or urinary incontinence.
      OUTCOMES: Pessaries can be successfully fitted in the majority of women with
      excellent satisfaction rates and minimal complications. EVIDENCE: PubMed and
      Medline were searched for articles published in English to September 2010, using
      the key words pessary, prolapse, incontinence, fitting, and complications.
      Results were restricted to systematic reviews, randomized control
      trials/controlled clinical trials, and observational studies. Searches were
      updated on a regular basis, and articles were incorporated in the guideline to
      May 2012. Grey (unpublished) literature was identified through searching the
      websites 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 quality of
      evidence was rated with use of the criteria described by the Canadian Task Force
      on Preventive Health Care. Recommendations for practice were ranked according to
      the method described by the Task Force (Table 1). BENEFITS, HARMS, AND COSTS:
      Women may choose a pessary for management of their prolapse and/or stress
      incontinence rather than opt for surgery. Major complications have been seen only
      with neglected pessaries. Minor complications such as vaginal discharge, odour,
      and erosions can usually be successfully treated. SUMMARY STATEMENTS AND
      RECOMMENDATION: Summary Statements 1. Most women can be successfully fitted with
      a pessary when they present with prolapse. (II-2) 2. Complications of pessary use
      are usually minor, and vaginal discharge is the most common complaint. (II-3) 3.
      Vaginal erosions can be treated with removal of the pessary and optional vaginal
      estrogen supplementation. (II-2) 4. Satisfaction rates with pessary use are very
      high. (II-2) Recommendation 1. Pessaries should be considered in all women
      presenting with symptomatic prolapse and/or urinary stress incontinence. (II-1A).

PMID- 23876649
TI  - [Relapse of Escherichia coli meningitidis due to sacral meningocele in Marfan
      syndrome, treated only with antibiotherapy].

PMID- 23876650
TI  - [New oral anticoagulant pharmacology].
AB  - All new oral anticoagulants are direct specific reversible inhibitors, either
      direct factor Xa inhibitors or inhibitors of thrombin. The pharmacokinetic of the
      new drugs is mediated by P- glycoprotein (P-gp) and metabolised by liver enzymes
      for some of them, principally cytochrome P450. That explains an important risk of
      drug interactions. The particularity of these new drugs is a priori a
      pharmacokinetic and pharmacodynamic profile more predictable involving no need
      for laboratory monitoring. In some clinical situations (risk of too high or too
      low exposure), a specific dose is proposed. 

PMID- 23876651
TI  - [An atypical polyradiculoneuritis].

PMID- 23876652
TI  - [New oral anticoagulants in the treatment of venous thromboembolism].
AB  - Rivaroxaban (with initial increased dosage) may be used as a stand-alone therapy
      in patients with venous thrombo-embolism. The development of new anticoagulant
      drugs opened several options in the management of venous thrombo-embolism. The
      efficacy and safety of these new oral anticoagulants in specific population as
      elderly and those with renal impairment deserve future research. At that time,
      only rivaroxaban is licensed in France, in the treatment of deep venous
      thrombosis. 

PMID- 23876653
TI  - Comparison of Synechocystis sp. PCC6803 and Nannochloropsis salina for lipid
      production using artificial seawater and nutrients from anaerobic digestion
      effluent.
AB  - The potential use of Synechocystis sp. PCC6803 (Synechocystis sp.) for lipid
      production using artificial seawater (ASW) medium supplemented with anaerobic
      digestion effluent (ADE) was investigated and compared to marine microalgae,
      Nannochloropsis salina (N. salina). Synechocystis sp. showed growth rates 83% and
      20% higher than N. salina at 3% and 6% ADE loading ratios, respectively,
      achieving the highest biomass productivity of 212 mg L(-1) d(-1) in semi
      continuous cultivation. The rapid growth of Synechocystis sp. was offset by its
      low lipid content, resulting in lipid productivities 7-28% lower than N. salina.
      The lipid productivity of Synechocystis sp. may be further improved by decreasing
      the harvesting interval during semi-continuous cultivation. Fatty acid analysis
      showed that lipids extracted from Synechocystis sp. contained higher palmitic
      acid (60.3+/-2.0%) and linoleic acid (20.0+/-1.6%), and had a higher cetane
      number and oxidative stability than those from N. salina.

PMID- 23876654
TI  - Photoautotrophic outdoor two-stage cultivation for oleaginous microalgae
      Scenedesmus obtusus XJ-15.
AB  - In this study, Scenedesmus obtusus XJ-15 was firstly selected from seven strains
      microalgae (Chlorophyta, Scenedesmaceae) and then cultivated using a two-stage
      strategy, which composed of fast cell growth in stage I and followed by lipid
      induction in stage II in 5-L flasks outdoors. In stage I, the biomass
      productivity was increased from 139.4 to 212.1 mg L(-1) d(-1). In stage II, lipid
      content was increased from 26.1% to 47.7% by adding NaCl into the culture. This
      two-stage process was also realized in an 140-L photobioreactor outdoors, with a
      biomass productivity of 86.5 mg L(-1) d(-1) and CO2 fixation rate of 170.0 mg L(
      1) d(-1) in the first stage, and high lipid content of 42.1% in the second stage.
      With such a culture strategy, the overall lipid productivity was improved and
      better biodiesel quality was obtained. These results suggested the
      photoautotrophic two-stage system was not only feasible but also effective.

PMID- 23876655
TI  - Relationship between starch and lipid accumulation induced by nutrient depletion
      and replenishment in the microalga Parachlorella kessleri.
AB  - Photosynthetic carbon partitioning into starch and neutral lipids, as well as the
      influence of nutrient depletion and replenishment on growth, pigments and storage
      compounds, were studied in the microalga, Parachlorella kessleri. Starch was
      utilized as a primary carbon and energy storage compound, but nutrient depletion
      drove the microalgae to channel fixed carbon into lipids as secondary storage
      compounds. Nutrient depletion inhibited both cellular division and growth and
      caused degradation of chlorophyll. Starch content decreased from an initial value
      of 25, to around 10% of dry weight (DW), while storage lipids increased from
      almost 0 to about 29% of DW. After transfer of cells into replenished mineral
      medium, growth, reproductive processes and chlorophyll content recovered within 2
      days, while the content of both starch and lipids decreased markedly to 3 or less
      % of DW; this suggested that they were being used as a source of energy and
      carbon.

PMID- 23876656
TI  - Biological decolorization of malachite green by Deinococcus radiodurans R1.
AB  - Cultures of Deinococcus radiodurans R1 were observed to decolorize malachite
      green (MG) dye. The effects of various factors on decolorization efficiency were
      investigated. The optimal decolorization temperature and pH ranges were 25-50
      degrees C and 6.0-8.0, respectively. With increasing initial MG concentration,
      the decolorization efficiency decreased, and the kinetic parameters, R(MG,max)
      and K(m) were 416.7 mg-MG/g-cell/h and 1033.7 mg/L, respectively. The D.
      radiodurans R1 cells were capable of tolerating and rapidly degrading high
      concentrations of the dye. When MG concentration was 200 mg/L, decolorization
      efficiency was up to 97.2% within 30 min. The intermediate products of MG
      biodegradation were 4-(dimethylamino)phenol and 4-(dimethylamino)benzophenone, as
      identified by gas chromatography/mass spectrometry analysis. Toxicity tests
      indicated that D. radiodurans R1 did not detoxify an MG solution completely, but
      clearly reduced its toxicity. This study demonstrated that this strain was an
      efficient degrader compared to other microorganisms.

PMID- 23876657
TI  - Agrotis segetum midgut putative receptor of Bacillus thuringiensis vegetative
      insecticidal protein Vip3Aa16 differs from that of Cry1Ac toxin.
AB  - Considering the fact that Agrotis segetum is one of the most pathogenic insects
      to vegetables and cereals in the world, particularly in Africa, the mode of
      action of Vip3Aa16 of Bacillus thuringiensis BUPM95 and Cry1Ac of the recombinant
      strain BNS3Cry-(pHTcry1Ac) has been examined in this crop pest. A. segetum
      proteases activated the Vip3Aa16 protoxin (90kDa) yielding three bands of about
      62, 45, 22kDa and the activated form of the toxin was active against this pest
      with an LC50 of about 86ng/cm(2). To be active against A. segetum, Cry1Ac
      protoxin was activated to three close bands of about 60-65kDa. Homologous and
      heterologous competition binding experiments demonstrated that Vip3Aa16 bound
      specifically to brush border membrane vesicles (BBMV) prepared from A. segetum
      midgut and that it does not inhibit the binding of Cry1Ac. Moreover, BBMV protein
      blotting experiments showed that the receptor of Vip3Aa16 toxin in A. segetum
      midgut differs from that of Cry1Ac. In fact, the latter binds to a 120kDa protein
      whereas the Vip3Aa16 binds to a 65kDa putative receptor. The midgut
      histopathology of Vip3Aa16 fed larvae showed vacuolization of the cytoplasm,
      brush border membrane lysis, vesicle formation in the goblet cells and
      disintegration of the apical membrane. The distinct binding properties and the
      unique protein sequence of Vip3Aa16 support its use as a novel insecticidal agent
      to control the crop pest A. segetum. 

PMID- 23876659
TI  - [The "controversy about intellectual property theft"].

PMID- 23876658
TI  - Development of a real-time PCR for detection of the oyster pathogen Nocardia
      crassostreae based on its homogeneous 16S-23S rRNA intergenic spacer region.
AB  - Nocardia crassostreae, the causative agent of Pacific oyster nocardiosis (PON),
      is a Gram-positive actinomycete bacterium associated with Pacific oyster
      (Crassostrea gigas) mortalities. Oysters infected with this bacterium have been
      reported previously from the west coast of North America and Japan. More
      recently, N. crassostreae was reported in oyster culture areas in the
      Netherlands. In this study, a sensitive real-time PCR for specific detection of
      N. crassostreae was developed, and the intra-species divergence of N.
      crassostreae from different geographical locations was studied. The 16S-23S rRNA
      intergenic spacer (ITS) region of N. crassostreae was sequenced for a number of
      infected oysters originating from the Netherlands, Japan and Canada. The sequence
      analyses showed an absence of genetic variation in the ITS region between N.
      crassostreae from different geographical locations. Based on these ITS sequences
      a species-specific and highly sensitive SYBR Green real-time PCR assay was
      developed to facilitate detection of N. crassostreae in oyster tissue. To
      evaluate this new detection tool for N. crassostreae a preliminary validation was
      carried out and real-time PCR results were compared with other detection methods
      (histology, conventional PCR and bacterial isolation) using field samples from
      Lake Grevelingen, the Netherlands. The genetic homogeneity in the ITS region
      between N. crassostreae from different geographical locations might be explained
      by the recent spread of the organism via the international trade in Pacific
      oysters for aquaculture purposes. However, the lack of genetic variation could
      also suggest that N. crassostreae is a genetically monomorphic species. 

PMID- 23876660
TI  - [How parents of adults persons with epilepsy do their best].
AB  - Epilepsy is a common and chronic disease which affects persons at every age. Even
      though medication can prevent seizures, epilepsy has implications for daily
      living. Sorrows, increased depression rates and restrictions in everyday life
      were documented among family caregivers of adult persons with epilpesy. To date,
      no study investigated how parents adapt to the epilepsy of adult children over
      time. The aim of this study was to explore experiences of parents of adult
      patients with epilepsy. Applying an interpretative phenomenological approach,
      narrative interviews with parents were reviewed to investigate parents'
      experiences. All parents described how they did their best to live with their
      situation. However, parents' experiences were distinctive and can be described
      as: "Being on the way together", "walking on a thightrope" and "struggling and
      caring all along". Using paradigm cases to describe what the epilepsy of their
      adult children ment to parents allowed to consider the context of these parents'
      experiences and enhanced understanding. As parents continue to support their
      adult children with epilepsy they should be included in specialist counselling
      and involved in care planning of their adult children. 

PMID- 23876662
TI  - [Timing of dressing removal in the healing of surgical wounds by primary
      intention: a meta-analysis].
AB  - An appropriate postoperative wound management helps to prevent surgical site
      infections. However, ideal timing of dressing removal is an unresolved issue in
      current practice. The objective of this systematic review therefore was to
      provide a comprehensive synthesis of existing evidence concerning the efficacy of
      different periods of postoperative dressing removal in surgical wounds which are
      healing by primary intention. We searched MEDLINE, EMBASE, CINAHL, The Cochrane
      Library (all in August 2011), and hand-searched additional sources. All
      randomised controlled trials that were comparing different periods of leaving
      dressings in place, including not dressing the surgical site at all, and covering
      wounds until suture removal were included. We conducted our systematic review and
      meta-analysis in accordance with the recommendations of the Cochrane
      Collaboration. Eight trials with a total of 2097 participants were included in
      our meta-analysis. All studies were at high or unclear risk of bias. This meta
      analysis did not show a higher rate of wound infections or other wound
      complications associated with an early dressing removal in wounds that are
      healing by primary intention: risk difference (RD) -0.01; 95%-confidence interval
      (CI) -0.03, 0.01. However, conclusions are limited due to bad study quality of
      included studies. Finally more sound research is needed.

PMID- 23876661
TI  - [How do nurses in psychiatric institutions assess suicide risk? A survey in the
      German-speaking part of Switzerland].
AB  - In the interdisciplinary treatment process nurses play an important role,
      assessing suicide risk. To cope with this responsibility, the use of assessment
      instruments is recommended. Although a lot of instruments exist to assess the
      risk of suicide, nurses do not use them consistently. This cross-sectional study
      seeks to answer the following questions: How do nurses assess the suicidality of
      patients of psychiatric hospitals in the German speaking part of Switzerland? Do
      they use assessment instruments and if so, which ones? Ward nurses in every
      psychiatric hospital (n = 32) were asked about the state of the nursing practice
      in assessing the suicide risk by means of an electronic questionnaire. The
      following results emerged: Nurses use instruments to assess suicide risk on about
      half of the wards (n = 119, 50.63%). 13% of the mentioned instruments are
      research-based. Nurses mostly assess suicide endangerment in the case of a
      presumed danger, less often at admission and least often during the discharge
      process. As suicidality is assessed mostly when nurses assume a danger in this
      study, and due to the fact that suicides most frequently occur shortly prior to
      or during the discharge process, an expansion of or the introduction of the
      assessment is recommended before the discharge process.

PMID- 23876663
TI  - [Nursing ethics and the access to nursing care].
AB  - The increasing number of ethical issues highlighted in everyday nursing care
      demonstrates the connectedness between nursing ethics and nursing practice.
      However, what is the role of ethical theories in this context? This question will
      be examined in this article by analysing the contribution made by the ethics of
      care, in particular in understandings of gender roles, asymmetries of power,
      professional knowledge and experience. The adoption and criticism of an emergent
      nursing ethics is discussed and stated from different viewpoints. The actuality
      of the caring approach is affirmed by a new reading of the given situation. This
      article first describes the traditional perception of nurses as marginalised
      actors in the health sector. By making reference to the current and growing
      global scarcity of nursing care, it contends that nursing will no longer be
      marginalised, but instead at the centre of public health attention and
      reputation. Nevertheless, marginalisation will persist by increasingly affecting
      the care receivers, especially those groups that are pushed to the fringes by the
      consequences of the healthcare market, such as persons of extreme old age,
      suffering from multiple morbidities, or with poor health literacy. Whereas the
      "classical" understanding of the ethics of care focuses on the nurse-patient
      relationship and on individual care and understanding of ethics, the new
      understanding confirms the classical, but adds an understanding of social ethics:
      caring for the access to care is seen as a main ethical goal of social justice
      within a nursing ethic. 

PMID- 23876664
TI  - [Qualitative data analysis: coding versus content analysis].

PMID- 23876671
TI  - Accuracy of diagnostic methods and surveillance sensitivity for human
      enterovirus, South Korea, 1999-2011.
AB  - The epidemiology of enteroviral infection in South Korea during 1999-2011
      chronicles nationwide outbreaks and changing detection and subtyping methods used
      over the 13-year period. Of 14,657 patients whose samples were tested, 4,762
      (32.5%) samples were positive for human enterovirus (human EV); as diagnostic
      methods improved, the rate of positive results increased. A seasonal trend of
      outbreaks was documented. Genotypes enterovirus 71, echovirus 30, coxsackievirus
      B5, enterovirus 6, and coxsackievirus B2 were the most common genotypes
      identified. Accurate test results correlated clinical syndromes to enterovirus
      genotypes: aseptic meningitis to echovirus 30, enterovirus 6, and coxsackievirus
      B5; hand, foot and mouth disease to coxsackievirus A16; and hand, foot and mouth
      disease with neurologic complications to enterovirus 71. There are currently no
      treatments specific to human EV infections; surveillance of enterovirus
      infections such as this study provides may assist with evaluating the need to
      research and develop treatments for infections caused by virulent human EV
      genotypes. 

PMID- 23876672
TI  - Incorporating prosocial behavior to promote physical activity in older adults:
      rationale and design of the Program for Active Aging and Community Engagement
      (PACE).
AB  - Despite the benefits of regular physical activity among older adults, physical
      activity rates are low in this population. The Program for Active Aging and
      Community Engagement (PACE) is an ongoing randomized controlled trial designed to
      compare the effects of two interventions on physical activity at 12 months among
      older adults. A total of 300 men and women aged 55 years or older will be
      randomized into either a healthy aging (HA) control intervention (n = 150), which
      is largely based upon educational sessions, or a prosocial behavior physical
      activity (PBPA) intervention (n = 150), which incorporates structured physical
      activity sessions, cognitive-behavioral counseling, and opportunities to earn
      food for donation to a regional food bank based on weekly physical activity and
      volunteering. The PBPA intervention is delivered at a local YMCA, and a regional
      grocery store chain donates the food to the food bank. Data will be collected at
      baseline, 3, 6, and 12 months. The primary outcome is physical activity as
      assessed by the Community Healthy Activities Model Program for Seniors (CHAMPS)
      Questionnaire at 12 months. Secondary outcomes include physical function and
      health-related quality of life. If successful, the PACE study will demonstrate
      that prosocial behavior and volunteerism may be efficaciously incorporated into
      interventions and will provide evidence for a novel motivating factor for
      physical activity.

PMID- 23876673
TI  - The impact of the availability of prevention studies on the desire to undergo
      predictive testing in persons at risk for autosomal dominant Alzheimer's disease.
AB  - Persons at risk for autosomal dominant neurodegenerative diseases provide the
      opportunity to efficiently test preventive interventions. Only a minority of such
      persons, however, choose to undergo revealing genetic testing, presenting a
      challenge to enrollment. Thirty-four preclinical Latinos (n = 26) and non-Latinos
      at risk for familial Alzheimer's disease (FAD) unaware of their genetic status
      were administered a questionnaire exploring their interest in undergoing
      revealing genetic testing at baseline and in the context of eligibility for four
      prevention trials of increasing invasiveness. Forty-four percent of subjects
      expressed a baseline interest in undergoing revealing testing which increased to
      85% in order to be eligible for a study of an oral drug "felt to be very safe."
      If there were a 50% chance of receiving placebo, this number dropped to 62% (p =
      0.02). Among those not interested in a study involving a 50% chance of receiving
      placebo, a range of 5% to 40% chance of receiving placebo was given as
      acceptable. For more invasive studies, living in the United States (as opposed to
      Mexico) positively influenced the likelihood of participating. Our data suggest
      that clinical trial designs in which persons must confront their genetic status
      prior to enrollment are feasible. Study designs to minimize the likelihood of
      being placed on placebo or provide the eventual administration of the drug
      through open-label extensions should be considered.

PMID- 23876674
TI  - Unifying and generalizing the two strands of evo-devo.
AB  - The emergence of evo-devo has had profound effects on how we study evolution.
      However, evo-devo research has tended to involve two general approaches, one
      being mechanistic and typological with a focus on simple, bimodal phenotypes, and
      the other being quantitative and focusing on multidimensional phenotypes without
      an understanding of underlying genetic mechanisms. Here, we suggest that, given
      recent technological advances in genomics, molecular biology, and morphometrics,
      evo-devo is poised for a reconciliation through which the field will realize far
      greater explanatory potential with respect to the patterns and processes that
      underlie adaptive phenotypic divergence. With this in mind, we review the recent
      literature and put forward a generalized evo-devo approach that is suitable for
      studies of quantitative traits in a range of taxa. 

PMID- 23876675
TI  - A direct comparison of early and late outcomes with three approaches to carotid
      revascularization and open heart surgery.
AB  - OBJECTIVES: The aim of this study was a comparison of risk-adjusted outcomes of 3
      approaches to carotid revascularization in the open heart surgery (OHS)
      population. BACKGROUND: Without randomized clinical trials, the best approach to
      managing coexisting severe carotid and coronary disease remains uncertain. Staged
      carotid endarterectomy (CEA) followed by OHS or combined CEA and OHS are commonly
      used. A recent alternative is carotid artery stenting (CAS). METHODS: From 1997
      to 2009, 350 patients underwent carotid revascularization within 90 days before
      OHS at a tertiary center: 45 staged CEA-OHS, 195 combined CEA-OHS, and 110 staged
      CAS-OHS. The primary composite endpoint was all-cause death, stroke, and
      myocardial infarction (MI). Staged CAS-OHS patients had higher prevalence of
      previous stroke (p = 0.03) and underwent more complex OHS. Therefore, the
      propensity score adjusted multiphase hazard function models with modulated
      renewal to account for staging, and competing risks were used. RESULTS: Using
      propensity analysis, staged CAS-OHS and combined CEA-OHS had similar early hazard
      phase composite outcomes, whereas staged CEA-OHS incurred the highest risk driven
      by interstage MI. Subsequently, staged CAS-OHS patients experienced significantly
      fewer late hazard phase events compared with both staged CEA-OHS (adjusted hazard
      ratio: 0.33; 95% confidence interval: 0.15 to 0.77; p = 0.01) and combined CEA
      OHS (adjusted hazard ratio: 0.35; 95% confidence interval: 0.18 to 0.70; p =
      0.003). CONCLUSIONS: Staged CAS-OHS and combined CEA-OHS are associated with a
      similar risk of death, stroke, or MI in the short term, with both being better
      than staged CEA-OHS. However, the outcomes significantly favor staged CAS-OHS
      after the first year.

PMID- 23876676
TI  - ROS signaling loops - production, perception, regulation.
AB  - Reactive oxygen species are recognized as important signaling components in a
      wide range of processes in plants and most other organisms. Reactive oxygen
      species are produced in different subcellular compartments in response to
      specific stimuli and the production is under tight control in order to avoid
      detrimental side-effects. Calcium signaling, protein phosphorylation and other
      signaling pathways are intimately involved in the control and coordination of
      reactive oxygen production. Any signal that should result in a specific response
      must eventually be perceived. Direct redox modification of transcription factors
      and other proteins are critical for the perception of intracellular reactive
      oxygen species; however, sensing of their extracellular counterparts awaits
      elucidation. 

PMID- 23876677
TI  - Submandibular cutaneous fistula.

PMID- 23876678
TI  - Patterns of visceral metastasis in cutaneous melanoma: a descriptive study.
AB  - BACKGROUND AND OBJECTIVES: Some types of cancer tend to spread to certain organs.
      In the case of melanoma, uveal melanoma spreads almost exclusively to the liver,
      while cutaneous melanoma spreads to the liver and other organs. Although
      important advances have been made in our understanding of the molecular
      mechanisms underlying melanoma, few recent studies have focused on the patterns
      of visceral metastasis in cutaneous melanoma. The aim of this study was to
      retrospectively investigate whether clinicopathologic variants of cutaneous
      melanoma and primary tumor site might be associated with pattern and time of
      onset of metastasis to visceral sites, including the central nervous system
      (CNS). MATERIALS AND METHODS: We included patients diagnosed with cutaneous
      melanoma between 1988 and 2009 with at least 2 years' follow-up. RESULTS: Of the
      1083 patients studied, 92 developed visceral metastasis. The CNS was affected in
      21 cases, the lungs in 24, the liver in 17, the digestive tract in 7, and
      multiple organs simultaneously in 23. Metastasis to the lungs, the liver, and the
      digestive tract occurred within 5 years in most cases, while metastasis to the
      CNS and multiple organs occurred later (>5 years in 38% and 43% of cases,
      respectively). CONCLUSIONS: Unlike uveal melanoma, cutaneous melanoma spreads to
      different organs without any particular predilection. We observed no significant
      associations between the site of visceral metastasis and either clinicopathologic
      variant or location of the primary tumor. Metastasis occurred within 5 years of
      diagnosis in most cases, but it can occur after 10 years.

PMID- 23876684
TI  - Gas chromatographic-mass spectrometric analysis of chemical volatiles in buffalo
      (Bubalus bubalis) urine.
AB  - Isolation of active fraction and characterization of chemosignals from urine have
      been attempted in several mammalian species in the recent years. The objective of
      this study was to identify the urinary volatiles across various reproductive
      stages of buffalo cow, namely, estrus, diestrus, and pregnancy, and in bull, by
      chemical extraction followed by gas chromatography-linked mass spectrometry (GC
      MS). Urine samples were collected from six buffalo cows at two different phases
      of estrous cycle, namely, estrus and diestrus. Besides, urinary samples were
      collected from five pregnant buffalo cows (60-75 days after artificial
      insemination (AI)) and six adult bulls. Thin-layer chromatography was performed
      as a preliminary test for qualitative comparison of different compounds extracted
      by organic solvents. Identification of the urinary compounds was carried out in a
      gas chromatograph (Perkin Elmer, Autosystem XL) linked to a mass spectrometer
      (Turbomass). The results of GC-MS analysis indicated the presence of 21 compounds
      with varying molecular weights and retention time, which were further categorized
      as diestrus-specific, pregnancy-specific, and bull-specific urinary compounds. No
      compound, however, could be identified as estrus-specific. We concluded that
      qualitative differences do exist in estrus, diestrus, and pregnant buffalo cow
      urine and in bull urine, as evidenced by GC-MS. 

PMID- 23876683
TI  - Moving beyond HLA: a review of nHLA antibodies in organ transplantation.
AB  - Given the finite graft life expectancy of HLA identical organ transplants and the
      recognition of humoral graft injury in the absence of donor directed anti-HLA
      antibodies, the clinical impact of antibodies against non-HLA (nHLA) antigens in
      transplant injury is being increasingly recognized. The recognition of the impact
      of nHLA antigen discrepancies between donor and recipient on transplant outcomes
      is timely given the advances in rapid and lower cost sequencing methods that can
      soon provide complete maps of all recipient and donor HLA and nHLA mismatch data.
      In this review, we present a summary of recent reports evaluating the role of
      nHLA antibodies and their relevance to the field of organ transplantation.

PMID- 23876685
TI  - [Bodypacking].

PMID- 23876679
TI  - Interplay between immune responses to HLA and non-HLA self-antigens in allograft
      rejection.
AB  - Recent studies strongly suggest an increasing role for immune responses against
      self-antigens (Ags) which are not encoded by the major histocompatibility complex
      in the immunopathogenesis of allograft rejection. Although, improved surgical
      techniques coupled with improved methods to detect and avoid sensitization
      against donor human leukocyte antigen (HLA) have improved the immediate and short
      term function of transplanted organs. However, acute and chronic rejection still
      remains a vexing problem for the long term function of the transplanted organ.
      Immediately following organ transplantation, several factors both immune and non
      immune mechanisms lead to the development of local inflammatory milieu which sets
      the stage for allograft rejection. Traditionally, development of antibodies (Abs)
      against mismatched donor HLA have been implicated in the development of Ab
      mediated rejection. However, recent studies from our laboratory and others have
      demonstrated that development of humoral and cellular immune responses against
      non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There
      are reports demonstrating that immune responses to self-Ags especially Abs to the
      self-Ags as well as cellular immune responses especially through IL17 has
      significant pro-fibrotic properties leading to chronic allograft failure. This
      review summarizes recent studies demonstrating the role for immune responses to
      self-Ags in allograft immunity leading to rejection as well as present recent
      evidence suggesting there is interplay between allo- and autoimmunity leading to
      allograft dysfunction.

PMID- 23876687
TI  - [If it's not only itching or burning: management of sexually transmitted
      infections (part 2].
AB  - In this second part about sexually transmitted infections (STI) we focus on the
      commonest pathogens related with genital ulcer disease, including Herpes simplex
      virus, Treponema pallidum and Chlamydia trachomatis. As most of these pathogens
      can cause long-term sequelae if left untreated it is of upmost importance to be
      familiar with the clinical manifestations and current diagnostic and therapeutic
      management. Most recent published international guidelines are reviewed to
      provide an updated overview. 

PMID- 23876688
TI  - [Cytoreductive surgery and HIPEC: a curative strategy for primary and secondary
      peritoneal tumors].
AB  - In patients with peritoneal carcinomatosis, cytoreductive surgery (CRS) and
      hyperthermic intraperitoneal chemotherapy (HIPEC) offers a chance for long term
      survival in well selected patients. During cytoreductive surgery, all
      macroscopically visible tumors needs to be resected before HIPEC is performed in
      the same procedure. The aim of HIPEC is eradication of microscopic tumor cells
      after radical surgery. Perioperative morbidity and mortality are comparable with
      other major surgical procedures. Patients with peritoneal carcinomatosis from
      tumors of the appendix, the colon or primary peritoneal mesothelioma are
      currently recommended for evaluation of CRS/HIPEC in an interdisciplinary
      setting. 

PMID- 23876689
TI  - [The future of neonatology: possibilities and limitations].
AB  - Neonatology is a form of general medicine which focuses on the beginning of life
      and lays its main emphasis on the conversion from intrauterine to extrauterine
      life. Over the last 50 years, the neonatal mortality in Switzerland dropped from
      25 to 3 per one-thousand liveborns. Today, the greatest challenges are extremely
      preterm infants and infants with complex malformations. Highly specialized
      intensive care enables survival in both high-risk groups but a significant number
      of children surviving with severe sequelae remain. This calls for research aiming
      at better understanding and supporting the adaptational changes and may
      simultaneously lead to ethical dilemmas about the limitation of intensive care.
      Since 1996, the Swiss Neonatal Network & Follow-up Group documents in high-risk
      infants the initial hospitalization at birth as well as the psychomotor
      development and quality of life until school age and beyond. 

PMID- 23876690
TI  - [Diagnosis and management of haemoptysis].
AB  - Haemoptysis is defined as the expectoration of blood or bloody streaking of the
      sputum. The list of possible underlying differential diagnoses is broad, and the
      cause of haemoptysis depends on the origin of the individual patient. Patients
      with minor haemoptysis can often be managed in the outpatient setting. In
      contrast, patients with major haemoptysis require immediate in-hospital
      diagnostic workup and therapy. Patients with major haemoptysis should be managed
      by a multidisciplinary team consisting of Pulmonologists, Critical Care
      Physicians/Anaesthesiologists, Interventional Radiologists, and Thoracic
      Surgeons. In major haemoptysis, airway maintenance, adequate gas exchange, and
      haemodynamic stabilization are mandatory. In this article, the recommended
      diagnostic and therapeutic steps in patients with major haemoptysis (particularly
      computed tomography, laboratory analyses, bronchoscopy, and bronchial artery
      embolization) are presented and discussed. 

PMID- 23876691
TI  - [A deceptive gut feeling].
AB  - We report the case of a 58 year old man with unspecific lower abdominal pain,
      respiratory failure and shock. An acute aortic syndrome and a massive pulmonary
      embolism were excluded, and a coronary angiography for suspected acute myocardial
      infarction was performed, with detection of a high-grade stenosis of the left
      main coronary artery. A percutaneous coronary intervention was needed. We discuss
      the difficulty to distinguish an acute aortic syndrome, an acute coronary
      syndrome, and a massive pulmonary embolism in the emergency situation. In
      addition we discuss the difficulty of detecting a left main coronary artery
      stenosis in the ECG. 

PMID- 23876692
TI  - [Interpretation of arterial blood gas analyses].

PMID- 23876693
TI  - [Colchicine is not just for gout, but is also effective for coronary heart
      disease].

PMID- 23876694
TI  - [New anticoagulants, new emergencies?].

PMID- 23876699
TI  - Expression of Pisum sativum PsAO3 gene, which encodes an aldehyde oxidase
      utilizing abscisic aldehyde, is induced under progressively but not rapidly
      imposed drought stress.
AB  - Aldehyde oxidase (AO; EC 1.2.3.1) catalyzes the final step of abscisic acid (ABA)
      biosynthesis, which is the oxidation of abscisic aldehyde (ABAld) to ABA. Gene
      expression analyses indicate that the stress-induced Pisum sativum PsAOgamma
      isoform, which effectively uses ABAld as a substrate, is encoded by the PsAO3
      gene. PsAO3 was heterologously expressed in Pichia pastoris and the recombinant
      PsAO3 protein revealed substrate preferences highly similar to the native
      PsAOgamma protein present in the pea leaves and roots. Both proteins prefer
      indole-3-aldehyde and naphthaldehyde as substrates, although high activities
      against abscisic aldehyde and citral were also observed. The Km values of PsAO3
      for naphthaldehyde and abscisic aldehyde (4.6 and 5.1 MUM, respectively) were the
      lowest among the substrates tested. PsAO3 activity was almost completely
      inhibited by potassium cyanide, diphenyleneiodonium, and methanol. Rapidly
      imposed drought stress did not increase the level of PsAO3 mRNA or activity of
      any AO isoform, although an enhanced ABA accumulation and induction of PsNCED2
      and -3 (9-cis-epoxycarotenoid dioxygenase; EC 1.13.11.51) expression, both in the
      pea roots and leaves, was observed. During a progressively induced drought, the
      level of PsAO3 transcript and PsAOgamma activity increased significantly in the
      roots and leaves, whereas ABA accumulation occurred only in the leaves where it
      was accompanied by induction of the PsNCED3 expression. Therefore, we suppose
      that next to NCED, also AO (mainly PsAOgamma) might be involved in regulation of
      the drought-induced ABA synthesis. However, while the "constitutive activity" of
      PsAOgamma is sufficient for the fast generation of ABA under rapid drought
      stress, the enhanced PsAOgamma activity is required for the progressive and long
      term ABA accumulation in the leaves under progressive drought stress.

PMID- 23876702
TI  - A review of current agents for anticoagulation for the critical care
      practitioner.
AB  - There has been a tremendous boom in the arena of anticoagulant therapy recently.
      Although the indications for these agents reside in the noncritical care
      environment, over time, the impact of these agents have infiltrated the critical
      care environment particularly due to devastating complications with associated
      use. With so many newer agents on the market or coming down the pipeline, it is
      easy to become overwhelmed. It is important that the critical care practitioner
      does not ignore these agents but becomes familiar with them to better prepare for
      the management of patients on one or more anticoagulant agents in the intensive
      care unit. To equip the critical care practitioners with the knowledge about
      commonly used anticoagulants, we provide an extensive review of the pharmacology,
      indications, and adverse effects related to these agents as well as suggestions
      on preventing or managing complications. 

PMID- 23876701
TI  - Facilitators and barriers to initiating change in medical intensive care unit
      survivors with alcohol use disorders: a qualitative study.
AB  - PURPOSE: Alcohol abuse and dependence are collectively referred to as alcohol use
      disorders (AUD). An AUD is present in up to one third of patients admitted to an
      intensive care unit (ICU). We sought to understand the barriers and facilitators
      to change in ICU survivors with an AUD to provide a foundation upon which to
      tailor alcohol-related interventions. METHODS: We used a qualitative approach
      with a broad constructivist framework, conducting semistructured interviews in
      medical ICU survivors with an AUD. Patients were included if they were admitted
      to 1 of 2 medical ICUs and were excluded if they refused participation, were
      unable to participate, or did not speak English. Digitally recorded and
      professionally transcribed interviews were analyzed using a general inductive
      approach and grouped into themes. RESULTS: Nineteen patients were included, with
      an average age of 51 (interquartile range, 36-51) years and an average Acute
      Physiology and Chronic Health Evaluation II score of 9 (interquartile range, 5
      13); 68% were white, 74% were male, and the most common reason for admission was
      alcohol withdrawal (n=8). We identified 5 facilitators of change: empathy of the
      inpatient health care environment, recognition of accumulating problems,
      religion, pressure from others to stop drinking, and trigger events. We
      identified 3 barriers to change: missed opportunities, psychiatric comorbidity,
      and cognitive dysfunction. Social networks were identified as either a barrier or
      facilitator to change depending on the specific context. CONCLUSIONS: Alcohol
      related interventions to motivate and sustain behavior change could be tailored
      to ICU survivors by accounting for unique barriers and facilitators.

PMID- 23876703
TI  - The current state of fellowship training in pulmonary artery catheter placement
      and data interpretation: a national survey of pulmonary and critical care
      fellowship program directors.
AB  - PURPOSE: Given decreasing use of pulmonary artery (PA) catheterization, we sought
      to evaluate whether current pulmonary and critical care fellows have adequate
      opportunity to obtain proficiency in PA catheter placement and data
      interpretation. METHODS: All US pulmonary and critical care program directors
      were invited to participate in an anonymous online survey regarding current
      training opportunities in PA catheterization. RESULTS: The response rate was 51%
      (69/136). Eighty-three percent reported that the number of PA catheterizations
      performed by fellows within their program has decreased in the past decade. Fifty
      four percent estimated that their fellows currently participate in less than 10
      supervised procedures during fellowship. The most frequently identified barriers
      to training were procedure volume and reluctance to place PA catheters in the
      medical intensive care unit. Forty-three percent of respondents agreed that
      training in PA catheter placement is currently adequate within their program, and
      55% agreed that training in data interpretation is adequate. Only 39% of
      respondents believe that PA catheter placement should continue to be an
      Accreditation Council for Graduate Medical Education training requirement.
      CONCLUSIONS: Many current pulmonary and critical care fellows do not have the
      opportunity to gain proficiency in PA catheterization. Fellowship training
      programs should consider alternate means of training fellows in PA catheter data
      interpretation, such as simulation.

PMID- 23876704
TI  - Evaluation of glucose variability when converting from insulin infusion to basal
      bolus regimen in a surgical-trauma intensive care unit.
AB  - PURPOSE: This study aimed to identify predictive factors resulting in glucose
      values greater than 200 mg/dL in patients with trauma transitioned from an
      insulin infusion to a basal-bolus subcutaneous insulin regimen. MATERIALS AND
      METHODS: Thirty-nine patients with trauma on goal enteral nutrition in the
      intensive care unit receiving an insulin infusion for at least 48 hours and
      transitioned to a basal-bolus regimen were retrospectively identified. RESULTS:
      Ten patients had hyperglycemic events after transition. Hyperglycemia was
      significantly associated with increased age (42 [17] years vs 56 [13] years,
      P=.02), admission glucose (128 [39] mg/dL vs 214 [91] mg/dL, P=.015), and insulin
      drip rate 48 hours before transition (87 [38] units/d vs 127 [49] units/d,
      P=.012). There was no difference between groups with respect to injury severity,
      demographics, or physiologic parameters. Multiple regression analysis revealed
      that increased age (odds ratio [OR], 1.215 [1.000-1.477]; P=.05), increased
      admission blood glucose (OR, 1.053 [1.006-1.101]; P=.025), and higher insulin
      infusion rates 48 hours before transition (OR, 1.061 [1.009-1.116]; P=.020)
      predisposed patients to severe hyperglycemic episodes. CONCLUSIONS: Older
      patients with trauma and patients with higher blood glucose on admission are more
      likely to experience severe hyperglycemia when transitioned to basal-bolus
      glucose control. Higher insulin infusion rates at 48 hours before transition are
      also associated with severe hyperglycemia.

PMID- 23876705
TI  - Low-molecular-weight DNA replication intermediates in Escherichia coli: mechanism
      of formation and strand specificity.
AB  - Chromosomal DNA replication intermediates, revealed in ligase-deficient
      conditions in vivo, are of low molecular weight (LMW) independently of the
      organism, suggesting discontinuous replication of both the leading and the
      lagging DNA strands. Yet, in vitro experiments with purified enzymes replicating
      sigma-structured substrates show continuous synthesis of the leading DNA strand
      in complete absence of ligase, supporting the textbook model of semi
      discontinuous DNA replication. The discrepancy between the in vivo and in vitro
      results is rationalized by proposing that various excision repair events nick
      continuously synthesized leading strands after synthesis, producing the observed
      LMW intermediates. Here, we show that, in an Escherichia coli ligase-deficient
      strain with all known excision repair pathways inactivated, new DNA is still
      synthesized discontinuously. Furthermore, hybridization to strand-specific
      targets demonstrates that the LMW replication intermediates come from both the
      lagging and the leading strands. These results support the model of discontinuous
      leading strand synthesis in E. coli. 

PMID- 23876707
TI  - Progress in detecting genetic alterations and their association with human
      disease.
AB  - The completion of the Human Genome Project provided a reference sequence to which
      researchers could compare sequences from individual patients in the hope of
      identifying disease-causing mutations. However, this still necessitated candidate
      gene testing or a very limited screen of multiple genes using Sanger sequencing.
      With the advent of high-throughput Sanger sequencing, it became possible to
      screen hundreds of patients for alterations in hundreds of genes. This process
      was time consuming and limited to a few locations/institutions that had the space
      to house tens of sequencing equipment. The development of next generation
      sequencing revolutionized the process. It is now feasible to sequence the entire
      exome of multiple individuals in about 10 days. However, this meant that a
      massive amount of data needed to be filtered to identify the relevant alteration.
      This is presently the rate-limiting step in providing a convincing association
      between a genetic alteration and a human disorder. 

PMID- 23876706
TI  - Structural mechanism of replication stalling on a bulky amino-polycyclic aromatic
      hydrocarbon DNA adduct by a y family DNA polymerase.
AB  - Polycyclic aromatic hydrocarbons and their nitro derivatives are culprits of the
      detrimental health effects of environmental pollution. These hydrophobic
      compounds metabolize to reactive species and attach to DNA producing bulky
      lesions, such as N-[deoxyguanosine-8-yl]-1-aminopyrene (APG), in genomic DNA. The
      bulky adducts block DNA replication by high-fidelity polymerases and compromise
      replication fidelities and efficiencies by specialized lesion bypass polymerases.
      Here we present three crystal structures of the DNA polymerase Dpo4, a model
      translesion DNA polymerase of the Y family, in complex with APG-lesion-containing
      DNA in pre-insertion and extension stages. APG is captured in two conformations
      in the pre-insertion complex; one is highly exposed to the solvent, whereas the
      other is harbored in a shallow cleft between the finger and unique Y family
      little finger domain. In contrast, APG is in a single conformation at the
      extension stage, in which the pyrene ring is sandwiched between the little finger
      domain and a base from the turning back single-stranded template strand.
      Strikingly, a nucleotide intercalates the DNA helix to form a quaternary complex
      with Dpo4, DNA, and an incoming nucleotide, which stabilizes the distorted DNA
      structure at the extension stage. The unique APG DNA conformations in Dpo4
      inhibit DNA translocation through the polymerase active site for APG bypass. We
      also modeled an insertion complex that illustrates a solvent-exposed pyrene ring
      contributing to an unstable insertion state. The structural work combined with
      our lesion replication assays provides a novel structural mechanism on bypass of
      DNA adducts containing polycyclic aromatic hydrocarbon moieties. 

PMID- 23876708
TI  - A novel assay for assessing juxtamembrane and transmembrane domain interactions
      important for receptor heterodimerization.
AB  - Understanding the basis of specificity in receptor homodimerization versus
      heterodimerization is essential in determining the role receptor plays in signal
      transduction. Specificity in each of the interfaces formed during signal
      transduction involves cooperative interactions between receptor extracellular,
      transmembrane (TM), and cytoplasmic domains. While methods exist for studying
      receptor heterodimerization in cell membranes, they are limited to either TM
      domains expressed in an inverted orientation or capture only heterodimerization
      in a single assay. To address this limitation, we have developed an assay (DN
      AraTM) that enables simultaneous measurement of homodimerization and
      heterodimerization of type I receptor domains in their native orientation,
      including both soluble and TM domains. Using integrin alphaIIb and RAGE (receptor
      for advanced glycation end products) as model type I receptor systems, we
      demonstrate both specificity and sensitivity of our approach, which will provide
      a novel tool to identify specific domain interactions that are important in
      regulating signal transduction. 

PMID- 23876709
TI  - The interaction of a nanoscale coherent helium-ion probe with a crystal.
AB  - Thickness fringing was recently observed in helium ion microscopy (HIM) when
      imaging magnesium oxide cubes using a 40 keV convergent probe in scanning
      transmission mode. Thickness fringing is also observed in electron microscopy and
      is due to quantum mechanical, coherent, multiple elastic scattering attenuated by
      inelastic phonon excitation (thermal scattering). A quantum mechanical model for
      elastic scattering and phonon excitation correctly models the thickness fringes
      formed by the helium ions. However, unlike the electron case, the signal in the
      diffraction plane is due mainly to the channeling of ions which have first
      undergone inelastic thermal scattering in the first few atomic layers so that the
      origin of the thickness fringes is not due to coherent interference effects. This
      quantum mechanical model affords insight into the interaction of a nanoscale,
      focused coherent ion probe with the specimen and allows us to elucidate precisely
      what is needed to achieve atomic resolution HIM.

PMID- 23876711
TI  - The dynamics of collagen uncrimping and lateral contraction in tendon and the
      effect of ionic concentration.
AB  - Under tensile loading, tendon undergoes a number of unique structural changes
      that govern its mechanical response. For example, stretching a tendon is known to
      induce both the progressive "uncrimping" of wavy collagen fibrils and extensive
      lateral contraction mediated by fluid flow out of the tissue. However, it is not
      known whether these processes are interdependent. Moreover, the rate-dependence
      of collagen uncrimping and its contribution to tendon's viscoelastic mechanical
      properties are unknown. Therefore, the objective of this study was to (a) develop
      a methodology allowing for simultaneous measurement of crimp, stress, axial
      strain and lateral contraction in tendon under dynamic loading; (b) determine the
      interdependence of collagen uncrimping and lateral contraction by testing tendons
      in different swelling conditions; and (c) assess how the process of collagen
      uncrimping depends on loading rate. Murine flexor carpi ulnaris (FCU) tendons in
      varying ionic environments were dynamically stretched to a set strain level and
      imaged through a plane polariscope with the polarizer and analyzer at a fixed
      angle. Analysis of the resulting images allowed for direct measurement of the
      crimp frequency and indirect measurement of the tendon thickness. Our findings
      demonstrate that collagen uncrimping and lateral contraction can occur
      independently and interstitial fluid impacts tendon mechanics directly.
      Furthermore, tensile stress, transverse contraction and degree of collagen
      uncrimping were all rate-dependent, suggesting that collagen uncrimping plays a
      role in tendon's dynamic mechanical response. This study is the first to
      characterize the time-dependence of collagen uncrimping in tendon, and
      establishes structure-function relationships for healthy tendons that can be used
      to better understand and assess changes in tendon mechanics after disease or
      injury. 

PMID- 23876712
TI  - Predicting bone remodeling around tissue- and bone-level dental implants used in
      reduced bone width.
AB  - The objective of this study was to predict time-dependent bone remodeling around
      tissue- and bone-level dental implants used in patients with reduced bone width.
      The remodeling of bone around titanium tissue-level, and titanium and titanium
      zirconium alloy bone-level implants was studied under 100 N oblique load for one
      month by implementing the Stanford theory into three-dimensional finite element
      models. Maximum principal stress, minimum principal stress, and strain energy
      density in peri-implant bone and displacement in x- and y- axes of the implant
      were evaluated. Maximum and minimum principal stresses around tissue-level
      implant were higher than bone-level implants and both bone-level implants
      experienced comparable stresses. Total strain energy density in bone around
      titanium implants slightly decreased during the first two weeks of loading
      followed by a recovery, and the titanium-zirconium implant showed minor changes
      in the axial plane. Total strain energy density changes in the loading and
      contralateral sides were higher in tissue-level implant than other implants in
      the cortical bone at the horizontal plane. The displacement values of the
      implants were almost constant over time. Tissue-level implants were associated
      with higher stresses than bone-level implants. The time-dependent biomechanical
      outcome of titanium-zirconium alloy bone-level implant was comparable to the
      titanium implant.

PMID- 23876713
TI  - Mobile platform for motion capture of locomotion over long distances.
AB  - Motion capture is usually performed on only a few steps of over-ground
      locomotion, limited by the finite sensing volume of most capture systems. This
      makes it difficult to evaluate walking over longer distances, or in a natural
      environment outside the laboratory. Here we show that motion capture may be
      performed relative to a mobile platform, such as a wheeled cart that is moved
      with the walking subject. To determine the person's absolute displacement in
      space, the cart's own motion must be localized. We present three localization
      methods and evaluate their performance. The first detects cart motion solely from
      the relative motion of the subject's feet during walking. The others use sensed
      motion of the cart's wheels to perform odometry, with and without an additional
      gyroscope to enhance sensitivity to turning about the vertical axis. We show that
      such methods are practical to implement, and with present-day sensors can yield
      accuracy of better than 1% over arbitrary distances. 

PMID- 23876714
TI  - A new method to analyze postural stability during a transition task from double
      leg stance to single-leg stance.
AB  - Time to stabilization (TTS) has been introduced as a method to analyze dynamic
      postural stability during jump and landing tasks, but has also been applied
      during the transition task from double-leg stance (DLS) to single-leg stance
      (SLS). However, the application of the originally described TTS technique during
      the latter task has some important limitations. The first goal of this study was
      to present an adapted version of the TTS technique to provide an effective
      alternative method to better analyze postural stability during the transition
      from DLS to SLS. The second goal was to study the influence of pathology and
      different speeds on postural stability outcomes. Fifteen healthy control subjects
      and 15 subjects with chronic ankle instability (CAI) performed the transition
      task on their preferred speed and as fast as possible, with eyes open and with
      eyes closed. Subjects with CAI performed the transition significantly slower when
      moving at their preferred speed with eyes closed. The time subjects needed to
      reach a new stability point was not discriminative between groups and largely
      dependent on movement speed. However, the amount of sway after this new stability
      point was significantly increased in the CAI group and when eyes were closed. The
      results of this study suggest that subjects with CAI have a decreased ability to
      overcome the postural perturbation created by the voluntary movement from DLS to
      SLS. Focusing only on TTS during the transition from DLS to SLS may lead at least
      in some cases to misinterpretations when assessing postural stability. 

PMID- 23876715
TI  - Biomechanical maturation of joint dynamics during early childhood: updated
      conclusions.
AB  - Dynamic parameters have been commonly explored to characterize the biomechanical
      maturation of children's gaits, i.e., age-revealing joint moment and power
      patterns similar to adult patterns. However, the literature revealed a large
      disparity of conclusions about maturation depending on the study, which was most
      likely due to an inappropriate scaling strategy and uncontrolled walking speed.
      With the first years of independent walking, a large growth in height and a large
      variability of dimensionless walking speed are observed. Moreover, the dynamic
      parameters were not well studied during early childhood. In the present study,
      seventy-five healthy children between 1 and 6 years of age were assessed during
      gait trials at a self-selected speed. Four hundred and sixty-two gait trials
      constituting five age groups with comparable dimensionless walking speeds were
      selected. 3D joint moments and the power of the lower limbs were computed and
      expressed using a dimensionless scaling strategy (according to body weight, leg
      length and the acceleration of gravity). Statistical analysis was performed to
      examine inter-group differences. Based on the current results, we concluded the
      biomechanical maturation of joint dynamics occurred around an age of 4 years for
      the ankle and between 6 and 7 years for the knee and the hip. Moreover, age group
      comparisons seemed more appropriate in young children using both the
      dimensionless strategy and a similar walking speed. Future investigations will be
      conducted on an older population (i.e., adding children older than 6 years) to
      clearly define the status of knee and hip biomechanical maturation. 

PMID- 23876716
TI  - Internet liability for gastroenterologists: select issues from social networking
      to doctor rating sites.

PMID- 23876717
TI  - Fungal disease following contaminated steroid injections: Exserohilum is ready
      for its close-up.
AB  - This Commentary highlights the article by Ritter et al. that reported the
      pathology associated with the recent fungal outbreak associated with contaminated
      methylprednisolone acetate injections. 

PMID- 23876718
TI  - Determination of renewable energy yield from mixed waste material from the use of
      novel image analysis methods.
AB  - Two novel techniques are presented in this study which together aim to provide a
      system able to determine the renewable energy potential of mixed waste materials.
      An image analysis tool was applied to two waste samples prepared using known
      quantities of source-segregated recyclable materials. The technique was used to
      determine the composition of the wastes, where through the use of waste component
      properties the biogenic content of the samples was calculated. The percentage
      renewable energy determined by image analysis for each sample was accurate to
      within 5% of the actual values calculated. Microwave-based multiple-point imaging
      (AutoHarvest) was used to demonstrate the ability of such a technique to
      determine the moisture content of mixed samples. This proof-of-concept experiment
      was shown to produce moisture measurement accurate to within 10%. Overall, the
      image analysis tool was able to determine the renewable energy potential of the
      mixed samples, and the AutoHarvest should enable the net calorific value
      calculations through the provision of moisture content measurements. The proposed
      system is suitable for combustion facilities, and enables the operator to
      understand the renewable energy potential of the waste prior to combustion. 

PMID- 23876719
TI  - SciX 2013 presented by FACSS. Sept 29th to Oct 7th, 2013. Milwaukee, WI.

PMID- 23876720
TI  - Methods and applications of Raman microspectroscopy to single-cell analysis.
AB  - Raman spectroscopy is a powerful biochemical analysis technique that allows for
      the dynamic characterization and imaging of living biological cells in the
      absence of fluorescent stains. In this review, we summarize some of the most
      recent developments in the noninvasive biochemical characterization of single
      cells by spontaneous Raman scattering. Different instrumentation strategies
      utilizing confocal detection optics, multispot, and line illumination have been
      developed to improve the speed and sensitivity of the analysis of single cells by
      Raman spectroscopy. To analyze and visualize the large data sets obtained during
      such experiments, sophisticated multivariate statistical analysis tools are
      necessary to reduce the data and extract components of interest. We highlight the
      most recent applications of single cell analysis by Raman spectroscopy and their
      biomedical implications that have enabled the noninvasive characterization of
      specific metabolic states of eukaryotic cells, the identification and
      characterization of stem cells, and the rapid identification of bacterial cells.
      We conclude the article with a brief look into the future of this rapidly
      evolving research area. 

PMID- 23876721
TI  - Sensitivity-enhanced transmission Raman spectroscopy.
AB  - Transmission Raman sensitivity for a representative commercial pharmaceutical
      tablet was increased by a factor of 40 using optics that returned lost laser and
      Raman photons to the tablet surface. A new achromatic one-way mirror is
      introduced that uses the spatial coherence of laser light to nondestructively
      force laser photons through the reflective tablet coating. Transmission Raman
      mapping and spatially offset Raman spectroscopy (SORS) mapping were developed and
      used to better understand the sensitivity-enhancement technology. Fundamental
      limitations of the sensitivity-enhancement approach are described and used to
      guide the design of the optics. The sensitivity-enhancement optics are compatible
      with commercial transmission Raman instruments. 

PMID- 23876722
TI  - Quantitative analysis of sodium carbonate and sodium bicarbonate in solid
      mixtures using Fourier transform infrared spectroscopy (FT-IR).
AB  - An analytical methodology is proposed based on constant ratio and absorbance
      correction methods to quantify sodium carbonate, Na2CO3 (1450 cm-1), and sodium
      bicarbonate, NaHCO3 (1000 cm-1, 1923 cm-1), in solid mixtures using Fourier
      transform infrared (FT-IR) spectroscopy. Potassium ferricyanide, K3Fe(CN)6
      (2117cm-1), was used as an internal standard to get characteristic parameters.
      NaHCO3 was quantified using the constant ratio method. Spectral interference of
      NaHCO3 in Na2CO3 (1450 cm-1) was corrected using the absorbance correction
      method. The corrected absorbance was successfully applied to quantify Na2CO3
      (1450 cm-1) in the mixture using the constant ratio method. The results obtained
      for simulated samples were satisfactory (relative standard deviation less than
      7%) for all samples.

PMID- 23876723
TI  - Human hair in the identification of cocaine abuse with cantilever-enhanced
      photoacoustic spectroscopy and principal component analysis.
AB  - In this study, a novel approach combining different techniques, including Fourier
      transform infrared (FT-IR) spectroscopy, photoacoustic spectroscopy (PAS) with an
      interferometric cantilever microphone, and principal component analysis (PCA)
      along with a proper data preprocessing procedure, have been used in the
      investigation of hair samples for cocaine abuse. Hair fibers from cocaine
      overdose patients have been measured using a simple procedure involving
      cantilever-enhanced photoacoustic Fourier transform infrared spectroscopy. In
      addition, a reference group of hair samples from subjects with no cocaine abuse
      has been measured. We present a first approach to discriminate the cocaine users
      from the reference group with the photoacoustic method and PCA. With proper data
      preprocessing methods, the two groups were successfully separated according to
      their spectra. The results were confirmed with two different classification
      methods independent of the principal component data analysis. 

PMID- 23876724
TI  - Diagnostic of laser-induced plasma using Abel inversion and radiation modeling.
AB  - A method based on matching synthetic and experimental emissivity spectra was
      applied to spatially resolved measurements of a laser-induced plasma ignited in
      argon at atmospheric pressure. The experimental emissivity spectra were obtained
      by Abel inversion of intensity spectra measured from a thin plasma slice
      perpendicular to the plasma axis. The synthetic spectra were iteratively
      calculated from an equilibrium model of plasma radiation that included free-free,
      free-bound, and bound-bound transitions. From both the experimental and synthetic
      emissivity spectra, spatial and temporal distributions of plasma temperature and
      number densities of plasma species (atoms, ions, and electrons) were obtained and
      compared. For the best-fit synthetic spectra, the temperature and number
      densities were read directly from the model; for experimental spectra, these
      parameters were obtained by traditional Boltzmann plot and Stark broadening
      methods. In both cases, the same spectroscopic data were used. Two approaches
      revealed a close agreement in electron number densities, but differences in
      plasma excitation temperatures and atom number densities. The trueness of the two
      methods was tested by the direct Abel transform that reconstructed the original
      intensity spectra for comparing them to the measured spectra. The comparison
      yielded a 9 and 13% difference between the reconstructed and experimental spectra
      for the numerical and traditional methods, respectively. It was thus demonstrated
      that the spectral fit method is capable of providing more accurate plasma
      diagnostics than the Boltzmann plot and Stark broadening methods. 

PMID- 23876725
TI  - Investigation of the photoionization properties of pharmaceutically relevant
      substances by resonance-enhanced multiphoton ionization spectroscopy and single
      photon ionization spectroscopy using synchrotron radiation.
AB  - The photoionization properties of the pharmaceutically relevant substances
      amantadine, diazepam, dimethyltryptamine, etomidate, ketamine, mescaline,
      methadone, and propofol were determined. At beamline U125/2-10m-NIM of the BESSY
      II synchrotron facility (Berlin, Germany) vacuum ultraviolet (VUV)
      photoionization spectra were recorded in the energy range 7.1 to 11.9 eV (174.6
      to 104.2 nm), showing the hitherto unknown ionization energies and fragmentation
      appearance energies of the compounds under investigation. Furthermore, (1+1)
      resonance-enhanced multiphoton ionization (REMPI) spectra of selected compounds
      (amantadine, diazepam, etomidate, ketamine, and propofol) were recorded by a
      continuous scan in the energy range between 3.6 and 5.7 eV (345 to 218 nm) using
      a tunable optical parametric oscillator (spectral resolution: 0.1 nm) laser
      system. The resulting REMPI wavelength spectra of these compounds are discussed
      and put into context with already known UV absorption data. Time-of-flight mass
      spectrometry was used for ion detection in both experiments. Finally, the
      implications of the obtained physical-chemical results for potential analytical
      applications are discussed. In this context, fast detection approaches for the
      considered compounds from breath gas using photoionization mass spectrometry and
      a rapid pre-concentration step (e.g., needle trap device) are of interest. 

PMID- 23876726
TI  - High-throughput, high-resolution Echelle deep-UV Raman spectrometer.
AB  - We constructed an ultrahigh-throughput, high-resolution ultraviolet (UV) Raman
      spectrograph that utilizes a high-efficiency filter-stage monochromator and a
      high-dispersion Echelle spectrograph. The spectrograph utilizes a total of six
      mirrors and two gratings, with an overall efficiency at 229 nm of ~18%. The
      limiting resolution of our spectrometer is 0.6 cm-1 full width half-maximum
      (FWHM), as measured for 229 nm Rayleigh scattering. Use of a 1 mm-wide entrance
      slit gives rise to an approximately 10 cm-1 FWHM resolution at 229 nm. The
      ultrahigh spectrograph throughput enables ultrahigh signal-to-noise ratio, deep
      UV Raman spectra that allow us to monitor <1% changes in peptide bond
      composition. The throughput is measured to be 35-fold greater than conventional
      deep UV Raman spectrometers.

PMID- 23876727
TI  - Host-guest molecular interactions in vanillin/amylose inclusion complexes.
AB  - The interaction of 4-hydroxy-3-methoxybenzaldehyde (vanillin) and Hylon VII due
      to the formation of an inclusion complex is studied using Fourier transform
      infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and
      circular dichroism (CD). The results confirm the close interaction among the
      different functional groups of vanillin and its host. In addition, a second case
      study was carried out with an amylose from a different source (100% amylose [APT
      III]). As a result, remarkable differences were found in the vanillin
      complexation capability of this amylose, which is only shown in solution by
      circular dichroism spectroscopy studies through a clear Cotton effect. This
      finding confirms the value of using CD studies, which shows that, depending on
      the amylose source, inclusion complexes can be found in solution, or both in
      solution and the coexisting precipitates, as shown using other techniques, such
      as X-ray diffraction (XRD) or differential scanning calorimetry (DSC). Moreover,
      solubility assays and complexation of both starches with iodine and subsequent
      absorption spectroscopy studies gives more information regarding the possible
      source of the starch encapsulation capability. Thus, Hylon VII shows higher
      capacity as vanillin encapsulant than APT III, showing the formation of inclusion
      complexes both in solution and solid phase, whereas APT III complexes are only
      perceivable in solution. 

PMID- 23876728
TI  - Optimizing Savitzky-Golay parameters for improving spectral resolution and
      quantification in infrared spectroscopy.
AB  - Calculating derivatives of spectral data by the Savitzky-Golay (SG) numerical
      algorithm is often used as a preliminary preprocessing step to resolve
      overlapping signals, enhance signal properties, and suppress unwanted spectral
      features that arise due to nonideal instrument and sample properties. Addressing
      these issues, a study of the simulated and measured infrared data by partial
      least-squares regression has been conducted. The simulated data sets were modeled
      by considering a range of undesired chemical and physical spectral anomalies and
      variations that can occur in a measured spectrum, such as baseline variations,
      noise, and scattering effects. The study has demonstrated the importance of the
      optimization of the SG parameters during the conversion of spectra into
      derivative form, specifically window size and polynomial order of the fitting
      curve. A specific optimal window size is associated with an exact component of
      the system being estimated, and this window size does not necessarily apply for
      some other component present in the system. Since the optimization procedure can
      be time-consuming, as a rough guideline spectral noise level can be used for
      assessment of window size. Moreover, it has been demonstrated that, when the
      extended multiplicative signal correction (EMSC) is used alongside the SG
      procedure, the derivative treatment of data by the SG algorithm must precede the
      EMSC normalization. 

PMID- 23876729
TI  - Characterization of novel lithium battery cathode materials by spectroscopic
      methods: the Li5+xFeO4 system.
AB  - The novel, lithium-rich oxide-phase Li5FeO4 (LFO) could, in theory, deliver a
      specific capacity >900 mAh/g when deployed as a cathode or cathode precursor in a
      battery with a lithium-based anode. However, research results to date on LFO
      indicate that less than one of the five Li+ cations can be reversibly de
      intercalated/re-intercalated during repetitive charging and discharging cycles.
      In the present research, the system Li5+xFeO4 with x values in the range of 0.0
      2.0 was investigated by a combination of Raman and X-ray absorption spectroscopic
      methods supported by X-ray diffraction (XRD) analysis in order to determine if
      the Li5FeO4 lattice would accommodate additional Li+ ions, with concomitant
      lowering of the valence on the FeIII cations. Both the Raman phonon spectra and
      the XRD patterns were invariant for all values of x, strongly indicating that
      additional Li+ did not enter the Li5FeO4 lattice. Also, Raman spectral results
      and high-resolution synchrotron XRD data revealed the presence of second-phase
      Li2O in all samples with x greater than 0.0. Synchrotron X-ray absorption
      spectroscopy at the Fe kalpha edge performed on the sample with a Li-Fe ratio of
      7.0 (i.e., x = 2.0) showed no evidence for the presence of FeII. This resistance
      to accepting more lithium into the Li5FeO4 structure is attributed to the
      exceedingly stable nature of high-spin FeIII in tetrahedral "FeIIIO4" structural
      units of Li5FeO4. Partial substitution of the FeIII with other cations could
      provide a path toward increasing the reversible Li+ content of Li5xFeO4-type
      phases.

PMID- 23876730
TI  - Quantitative determination of methanol and ethanol with synthetic calibration
      spectra in passive Fourier transform infrared remote sensing measurements.
AB  - A spectral synthesis strategy is introduced to help obtain estimates of path
      integrated concentrations in passive Fourier transform infrared (FT-IR) remote
      sensing measurements conducted during field-monitoring experiments. Obtaining
      quantitative information from passive infrared data is challenging because of the
      joint effects of temperature and concentration on spectral intensities. The
      collection of calibration data for use in modeling spectral intensities for a
      given set of experimental conditions is also costly and labor intensive. In the
      work presented here, a radiance model is defined for use in synthesizing
      calibration spectra that serve as inputs to partial least-squares (PLS) models
      that relate spectral intensities to path-integrated concentrations. The field
      data for which quantitative estimates are desired are used to estimate the
      background temperature associated with a given time and set of experimental
      conditions. Sample temperatures can be obtained through either experimental
      measurement or by estimating one calibration release. Given these temperatures,
      calibration data can be synthesized and the PLS model developed. This methodology
      is tested with stack monitoring data obtained from controlled releases of pure
      and mixture samples of heated ethanol and methanol. Experiments were conducted
      across 6 days with stack temperatures of 150 to 200  degrees C and with path
      integrated concentrations in the range of 10 to 300 parts per million meters.
      Median relative errors in the estimates of path-integrated concentration were
      typically in the range of 20% or less, with the best results observed at the
      higher stack temperatures. 

PMID- 23876731
TI  - Evaluation of local approaches to obtain accurate near-infrared (NIR) equations
      for prediction of ingredient composition of compound feeds.
AB  - This research work investigated new methods to improve the accuracy of intact
      feed calibrations for the near-infrared (NIR) prediction of the ingredient
      composition. When NIR reflection spectroscopy, together with linear models, was
      used for the prediction of the ingredient composition, the results were not
      always acceptable. Therefore, other methods have been investigated. Three
      different local methods (comparison analysis using restructured near-infrared and
      constituent data [CARNAC]), locally weighed regression [LWR], and LOCAL) were
      applied to a large (N = 20 320) and heterogeneous population of non-milled feed
      compounds for the NIR prediction of the inclusion percentage of wheat and
      sunflower meal, as representative of two different classes of ingredients.
      Compared with partial least-squares regression, results showed considerable
      reductions of standard error of prediction values for all methods and
      ingredients: reductions of 59, 47, and 50% with CARNAC, LWR, and LOCAL,
      respectively, for wheat, and reductions of 49, 45, and 43% with CARNAC, LWR, and
      LOCAL, respectively, for sunflower meal. These results are a valuable achievement
      in coping with legislation and manufacture requirements concerning the labeling
      of intact feedstuffs. 

PMID- 23876732
TI  - In situ diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS)
      study of formaldehyde adsorption and reactions on Pd-doped nano-gamma-Fe2O3
      films.
AB  - Palladium-doped nano-gamma-Fe2O3 films were printed on Al2O3 substrates by screen
      printing-injecting hybrid technology. X-ray diffraction and scanning electron
      microscopy techniques were used to characterize the phase structures and
      morphologies of the films, respectively. The sensitivity of the films to 100 ppm
      formaldehyde in air was investigated. The surface adsorption and reaction process
      between Pd-doped nano-gamma-Fe2O3 films and formaldehyde was studied by in situ
      diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) at different
      temperatures. Dioxymethylene, formate ions, polyoxymethylene, and adsorbed
      formaldehyde were detected when the Pd-doped nano-gamma-Fe2O3 films were exposed
      to 100 ppm formaldehyde at different temperatures. A possible mechanism of the
      reaction process is discussed.

PMID- 23876733
TI  - In situ attenuated total reflectance Fourier transform infrared (ATR FT-IR)
      spectroscopy monitoring of 1,2-butylene oxide polymerization reaction by using
      iterative concentration-guided classical least squares.
AB  - There has been rapid growth in the application of in situ optical spectroscopy
      techniques for reaction and process monitoring recently in both academia and
      industry. Vibrational spectroscopies such as mid-infrared, near-infrared
      spectroscopy, and Raman spectroscopy have proven to be versatile and informative.
      Accurate determination of concentrations, based on highly overlapped spectra,
      remains a challenge. As an example, 1,2-butylene oxide (BO) polymerization, an
      important industrial reaction, initiated by propylene glycol (PG) and catalyzed
      by KOH, is studied in this work in a semi-batch fashion by using in situ
      attenuated total reflectance Fourier transform infrared spectroscopy (ATR FT-IR)
      monitoring. The weak BO absorbance, the constantly changing interference from the
      product oligomers throughout the course of the reaction, and the change in BO
      spectral features with system polarity posed challenges for quantitative spectral
      analysis based on conventional methods. An iterative concentration-guided
      classical least-squares (ICG-CLS) method was developed to overcome these
      challenges. Taking advantage of the concentration-domain information, ICG-CLS
      enabled the estimation of the pure oligomer product spectra at different stages
      of the semi-batch process, which in turn was used to construct valid CLS models.
      The ICG-CLS algorithm provides an in situ calibration method that can be broadly
      applied to reactions of known order. Caveats in its applications are also
      discussed. 

PMID- 23876734
TI  - Automated quantitative spectroscopic analysis combining background subtraction,
      cosmic ray removal, and peak fitting.
AB  - An integrated concept for post-acquisition spectrum analysis was developed for in
      line (real-time) and off-line applications that preserves absolute spectral
      quantification; after the initializing parameter setup, only minimal user
      intervention is required. This spectral evaluation suite is composed of a
      sequence of tasks specifically addressing cosmic ray removal, background
      subtraction, and peak analysis and fitting, together with the treatment of two
      dimensional charge-coupled device array data. One may use any of the individual
      steps on their own, or may exclude steps from the chain if so desired. For the
      background treatment, the canonical rolling-circle filter (RCF) algorithm was
      adopted, but it was coupled with a Savitzky-Golay filtering step on the locus
      array generated from a single RCF pass. This novel only-two-parameter procedure
      vastly improves on the RCF's deficiency to overestimate the baseline level in
      spectra with broad peak features. The peak analysis routine developed here is an
      only-two-parameter (amplitude and position) fitting algorithm that relies on
      numerical line shape profiles rather than on analytical functions. The overall
      analysis chain was programmed in National Instrument's LabVIEW; this software
      allows for easy incorporation of this spectrum analysis suite into any LabVIEW
      managed instrument control, data-acquisition environment, or both. The strength
      of the individual tasks and the integrated program sequence are demonstrated for
      the analysis of a wide range of (although not necessarily limited to) Raman
      spectra of varying complexity and exhibiting nonanalytical line profiles. In
      comparison to other analysis algorithms and functions, our new approach for
      background subtraction, peak analysis, and fitting returned vastly improved
      quantitative results, even for "hidden" details in the spectra, in particular,
      for nonanalytical line profiles. All software is available for download. 

PMID- 23876735
TI  - Depth-resolved multilayer pigment identification in paintings: combined use of
      laser-induced breakdown spectroscopy (LIBS) and optical coherence tomography
      (OCT).
AB  - A detailed feasibility study on the combined use of laser-induced breakdown
      spectroscopy with optical coherence tomography (LIBS/OCT), aiming at a realistic
      depth-resolved elemental analysis of multilayer stratigraphies in paintings, is
      presented. Merging a high spectral resolution LIBS system with a high spatial
      resolution spectral OCT instrument significantly enhances the quality and
      accuracy of stratigraphic analysis. First, OCT mapping is employed prior to LIBS
      analysis in order to assist the selection of specific areas of interest on the
      painting surface to be examined in detail. Then, intertwined with LIBS, the OCT
      instrument is used as a precise profilometer for the online determination of the
      depth of the ablation crater formed by individual laser pulses during LIBS depth
      profile analysis. This approach is novel and enables (i) the precise in-depth
      scaling of elemental concentration profiles, and (ii) the recognition of layer
      boundaries by estimating the corresponding differences in material ablation rate.
      Additionally, the latter is supported, within the transparency of the object, by
      analysis of the OCT cross-sectional views. The potential of this method is
      illustrated by presenting results on the detailed analysis of the structure of an
      historic painting on canvas performed to aid planned restoration of the artwork. 

PMID- 23876736
TI  - Sequentially shifted excitation Raman spectroscopy: novel algorithm and
      instrumentation for fluorescence-free Raman spectroscopy in spectral space.
AB  - A novel Raman spectrometer is presented in a handheld format. The spectrometer
      utilizes a temperature-controlled, distributed Bragg reflector diode laser, which
      allows the instrument to operate in a sequentially shifted excitation mode to
      eliminate fluorescence backgrounds, fixed pattern noise, and room lights, while
      keeping the Raman data in true spectral space. The cost-efficient design of the
      instrument allows rapid acquisition of shifted excitation data with a shift time
      penalty of less than 2 s. The Raman data are extracted from the shifted
      excitation spectra using a novel algorithm that is typically three orders of
      magnitude faster than conventional shifted-excitation algorithms operating in
      spectral space. The superiority of the instrument and algorithm in terms of
      background removal and signal-to-noise ratio is demonstrated by comparison to FT
      Raman, standard deviation spectra, shifted excitation Raman difference
      spectroscopy (SERDS), and conventional multiple-shift excitation methods. 

PMID- 23876737
TI  - An important improvement in Ferron-timed spectrophotometry.
AB  - Ferron dosage ([Ferron]) is key to ferron-timed spectrophotometry (ferron assay).
      In order to clarify some important questions, the following studies were
      conducted: (1) The effect of [Ferron] on the sensitivity of total aluminum (AlT)
      determination was experimentally investigated and 27Al nuclear magnetic resonance
      (27Al NMR) spectroscopy was used to verify our developed Ferron assay; (2) the
      chemical equilibrium calculation was employed to analyze the effect of [Ferron]
      on the determination of AlT; and (3) the main reason for insufficient [Ferron]
      was further analyzed. This is the first study to standardize a ferron assay
      operating procedure.

PMID- 23876738
TI  - Thermal stability of intralipid optical phantoms.
AB  - We investigated the stability of light transmission through Intralipid-based
      optical phantoms in the wavelength range of 400-950 nm at temperatures between 35
      and 70  degrees C. Optical phantoms are materials commonly used to simulate the
      light scattering and absorption properties of biological materials. These
      simulations require the phantom to be optically stable. We demonstrate that the
      scattering properties of Intralipid remain stable at higher temperatures, varying
      less than 0.5%. We also present results that show this is not the case for
      absorption below 700 nm at 35 and 70  degrees C, with greater instability at 70 
      degrees C. For example, at 500 nm, the light intensity transmitted through 15 mm
      of Intralipid dropped 39% over 12 h. We demonstrate that oxidation of fatty acids
      in Intralipid could account for this effect and show, by flushing the system
      continuously with nitrogen gas, the instability is reduced. 

PMID- 23876739
TI  - Adipocyte and adipogenesis.
AB  - Adipocytes are the main constituent of adipose tissue and are considered to be a
      corner stone in the homeostatic control of whole body metabolism. Their primary
      function is to control energy balance by storing triacylglycerol in periods of
      energy excess and mobilizing it during energy deprivation. Besides the classical
      function of storing fat, adipocytes secrete numerous lipid and protein factors.
      Collectively they are considered to constitute a major endocrine organ which has
      a profound impact on the metabolism of other tissues, the regulation of appetite,
      insulin sensitivity, immunological responses and vascular disease. Adipogenesis
      is the process during which fibroblast like preadipocytes developed into mature
      adipocytes. Adipogenesis is a well-orchestrated multistep process that requires
      the sequential activation of numerous transcription factors, including the
      CCAAT/enhancer-binding protein (C/EBP) gene family and peroxisome proliferator
      activated receptor-gamma (PPAR-gamma). In order to reach maturity, these cells
      must go through two vital steps: adipocyte determination and adipocyte
      differentiation. Although many of the molecular details of adipogenesis are still
      unknown, several factors involved in this processes have been identified. Some
      stimulators include peroxisome proliferator-activated receptor gamma (PPAR
      gamma), insulin-like growth factor I (IGF-l), macrophage colony stimulating
      factor, fatty acids, prostaglandins and glucocorticoids. Inhibitors include
      glycoproteins, transforming growth factor-beta (TGF-beta), inflammatory cytokines
      and growth hormone. Beside these factors, there are others for example age,
      gender and life style that may affect this process in one way or another. An
      increase in the number and size of adipocytes causes white adipose tissue (WAT)
      to expand and this can lead to obesity. Adipogenesis can lead to central obesity
      if it occurs in the abdominal fat depot and peripheral obesity if it occurs in
      subcutaneous tissue. 

PMID- 23876741
TI  - Ventilation heterogeneity is associated with airway responsiveness in asthma but
      not COPD.
AB  - Airway hyperresponsiveness (AHR) occurs in both asthma and COPD. In older people
      with asthma, AHR is associated with increased acinar ventilation heterogeneity,
      but it is unknown if this association exists in COPD. Thirty one COPD and 19 age
      matched asthmatic subjects had measures of spirometry, lung volumes, exhaled
      nitric oxide, ventilation heterogeneity, and methacholine challenge. Indices of
      acinar (Sacin) and conducting (Scond) airway ventilation heterogeneity were
      calculated from the multiple breath nitrogen washout. Predictors of AHR were then
      determined. In COPD, AHR was predicted by lower Sacin and lower FVC (model
      r(2)=0.35, p=0.001). In asthma, AHR was predicted by higher Sacin and higher
      residual volume (model r(2)=0.62, p<0.001). These findings suggest that airway
      responsiveness in COPD and asthma is determined by underlying disease-specific
      processes, rather than a common pattern of physiological abnormality. 

PMID- 23876740
TI  - Allergen challenge during halothane compared to isoflurane anesthesia induces a
      more potent peripheral lung response.
AB  - Allergen instillation in anaesthetized vs. awake animals results in increased
      distribution of allergen in the lung. Halothane is a more potent bronchodilator
      of the small airways than isoflurane. As small airways contribute to asthma
      pathogenesis, we questioned whether intranasal challenge under halothane vs.
      isoflurane anesthesia would lead to an increase in allergen deposition in the
      lung periphery and, consequently, an enhanced allergic response. C57Bl/6 mice
      were sensitized twice and repeatedly challenged with ovalbumin (OA) under
      halothane or isoflurane anesthesia. After OA-challenge, in vivo lung function was
      measured and BAL performed. Peribronchial and peripheral inflammation, cytokine
      mRNA production and collagen deposition were assessed. Airway
      hyperresponsiveness, BAL eosinophilia, peripheral lung inflammation, IL-5 mRNA
      production and collagen deposition were significantly increased in halothane OA
      challenged compared to isoflurane OA-challenged mice. Airway challenge induced a
      higher level of airway hyperresponsiveness, inflammation and remodeling under
      halothane than isoflurane anesthesia in a murine model of asthma. These
      differences may be due to increased allergen deposition in the small airways. 

PMID- 23876742
TI  - Sleep and breathing. Foreword.

PMID- 23876743
TI  - Preoperative diagnosis of a solid pseudopapillary tumour of the pancreas by
      Endoscopic Ultrasound Fine Needle Biopsy: A retrospective case series.
AB  - BACKGROUND: A solid pseudopapillary tumour of the pancreas (SPTP) is a rare
      neoplasm. AIM: We herein present five cases of SPTP diagnosed using endoscopic
      ultrasound (EUS) guided fine-needle biopsy (FNB) using a needle with side
      fenestration (ProCore-needle). METHODS: From January 2011 to June 2012 in five
      patients with SPTP tissue acquisition was carried out with a 19-gauge (4
      patients) or a 22-gauge (one patient) needle. RESULTS: The mean age of the
      patients was 30.8 years, the mean lesion size was 49mm and the most common
      location was the tail of the pancreas (3 cases). When the samples were evaluated
      macroscopically, small core fragments were observed in all cases. A preoperative
      diagnosis of SPTP was made in all patients on the basis of the histocytological
      and characteristic immunophenotypic patterns and was confirmed at final surgical
      histology. CONCLUSIONS: In our experience, EUS-FNB is an effective and secure
      method for a preoperative diagnosis of SPTP.

PMID- 23876744
TI  - Impact of 2003 state regulation on raw oyster-associated Vibrio vulnificus
      illnesses and deaths, California, USA.
AB  - US vibriosis rates have increased since 1996, and many Vibrio vulnificus
      infections are fatal. In April 2003, California implemented a regulation
      restricting the sale of raw oysters harvested from the Gulf of Mexico during
      April 1-October 31, unless they were processed to reduce V. vulnificus to
      nondetectable levels. We analyzed California cases of V. vulnificus infection
      before and after the regulation's implementation and compared case data with data
      from other states. The annual number of reported V. vulnificus infections and
      deaths in California with patient's sole exposure to raw oysters dropped from 0
      to 6 cases and 0 to 5 deaths per year during 1991-2002, before implementation, to
      0 during 2003-2010, after implementation (p = 0.0005 for both). In other states,
      median annual numbers of similar cases and deaths increased slightly after 2002.
      The data strongly suggest that the 2003 regulation led to a significant reduction
      in reported raw oyster-associated V. vulnificus illnesses and deaths. 

PMID- 23876745
TI  - Prenatal versus postnatal maternal factors in the development of infection
      induced working memory impairments in mice.
AB  - Prenatal maternal infection is an environmental risk factor for
      neurodevelopmental psychiatric illness and disease-associated cognitive
      impairments. Modeling this epidemiological link in animals shows that prenatal
      immune challenge is capable of inducing long-lasting deficits in numerous
      cognitive domains. Here, we combined a neonatal cross-fostering design with a
      mouse model of prenatal immune challenge induced by maternal gestational
      treatment with the viral mimetic poly(I:C) to dissect the relative contribution
      of prenatal and postnatal maternal effects on the offspring. We show that
      offspring prenatally exposed to poly(I:C) display significant impairments in
      spatial matching-to-position working memory and spatial novelty presence
      regardless of whether they are raised by gestationally immune-challenged or non
      challenged control surrogate mothers. Likewise, prenatally immune challenged
      offspring exhibit reduced glutamic acid decarboxylase 65-kDa (GAD65) and 67-kDa
      (GAD67) gene expression in the adult medial prefrontal cortex and dorsal
      hippocampus largely independently of the postnatal rearing conditions. In
      addition, we confirm that being raised by a gestationally immune-challenged
      surrogate mother is sufficient to increase the offspring's locomotor response to
      systemic amphetamine treatment. Our data thus suggest that prenatal infection
      induced deficits in spatial short-term memory are mediated by prenatal maternal
      effects on the offspring. At the same time, our study adds further weight to the
      notion that being reared by a surrogate mother that experienced immune activation
      during pregnancy may constitute a risk factor for specific dopaminergic
      abnormalities. 

PMID- 23876746
TI  - Differential neuroendocrine and immune responses to acute psychosocial stress in
      women with type 1 bipolar disorder.
AB  - Bipolar disorder (BD) has been associated with immune imbalance, including
      lymphocyte activation and increased pro-inflammatory cytokines. Immune activation
      is part of stress response, and psychosocial stress has been implicated in the
      pathogenesis of psychiatric disorders. Here, we investigated the neuroendocrine
      and immune responses to acute psychosocial stress challenge in BD. Thirteen
      euthymic participants with type 1 BD and 15 healthy controls underwent the Trier
      Social Stress Test protocol (TSST). Blood samples were collected before and after
      TSST. Lymphocytes were isolated and stimulated in vitro to assess lymphocyte
      activation profile, lymphocyte sensitivity to dexamethasone, mitogen-activated
      protein kinase (MAPK) and nuclear factor kappa B (NF-kappaB) signaling by flow
      cytometry. Heart rate and salivary cortisol levels were monitored across the
      task. BD participants exhibited blunted stress responses as shown by reduced
      heart rate and salivary cortisol levels in comparison to healthy controls. BD was
      also associated with reduction in the percentage of regulatory T cells, but with
      expansion of activated T cells. When compared to controls, patients showed
      increased lymphocyte MAPK p-ERK and p-NF-kappaB signaling after the stress
      challenge, but exhibited a relative lymphocyte resistance to dexamethasone. In
      conclusion, stress-related neuroendocrine responses are blunted, associated with
      increased immune activation and lower sensitivity to glucocorticoids in BD. An
      inability in reducing NF-kappaB and MAPK signaling following TSST could be
      underlying the immune imbalance observed in BD. 

PMID- 23876748
TI  - Qualification of cardiac troponins for nonclinical use: a regulatory perspective.
AB  - The US Food and Drug Administration (FDA) Biomarker Qualification Review Team
      presents its perspective on the recent qualification of cardiac troponins for use
      in nonclinical safety assessment studies. The goal of this manuscript is to
      provide greater transparency into the qualification process and factors that were
      considered in reaching a regulatory decision. This manuscript includes an
      overview of the data that were submitted and a discussion of the strengths and
      shortcomings of these data supporting the qualification decision. The cardiac
      troponin submission is the first literature-based biomarker application to be
      reviewed by the FDA and insights gained from this experience may aid future
      submissions and help streamline the characterization and qualification of future
      biomarkers. 

PMID- 23876749
TI  - [Pitfalls of laboratory values].

PMID- 23876747
TI  - Depressive symptoms are associated with reduced neutrophil function in hip
      fracture patients.
AB  - Hip fracture is a common trauma in older adults with a high incidence of
      depression, which relates to poorer prognosis including increased risk of
      infection. Ageing is accompanied by reduced immunity, termed immunesenescence,
      resulting in increased susceptibility to infection. We examined whether physical
      trauma (hip fracture) and psychological distress (depressive symptoms) had
      additive effects upon the aged immune system that might contribute to poor
      outcomes after injury. Neutrophil function was assessed in 101 hip fracture
      patients (81 female) 6 weeks and 6 months after injury and 43 healthy age-matched
      controls (28 female). Thirty eight fracture patients had depressive symptoms at 6
      weeks. No difference in neutrophil phagocytosis of Escherichia coli was observed
      between controls and hip fracture patients, but superoxide production was
      significantly reduced in hip fracture patients with depressive symptoms compared
      with patients without symptoms (p=.001) or controls (p=.004) at 6 weeks.
      Superoxide production improved 6 months following fracture to the level seen in
      controls. We detected elevated serum cortisol, reduced dehydroepiandrosterone
      sulphate (DHEAS) and an increased cortisol:DHEAS ratio in fracture patients with
      depressive symptoms compared with patients without depressive symptoms or
      controls at 6 weeks and 6 months after injury. Serum IL6, TNFalpha and IL10 were
      higher among patients with depressive symptoms at 6 weeks. The cortisol:DHEAS
      ratio and IL6 levels related to depressive symptom scores but not to neutrophil
      function. In conclusion, depressive symptoms related to poorer neutrophil
      function after hip fracture, but this was not driven by changes in stress hormone
      or cytokine levels.

PMID- 23876750
TI  - [Pitfall in coagulation tests].
AB  - Coagulation assays are prone to pre-analytical problems and results may be
      influenced by varying clinical and pharmaceutical aspects. Particularly
      anticoagulants interact with coagulation testing in many ways. Thromboplastin
      time will be prolonged dose-dependently in patients taking vitamin K antagonists;
      moreover the new oral anticoagulants have been shown to have variable impact on
      the results of the thromboplastin time as well as on other coagulation tests,
      depending on the mechanism of action of these new drugs as well as on the
      mechanism of the coagulation test. When measuring anti-Xa activity it should be
      realised that all drugs with anti-Xa activity will influence the result, which
      means not only heparins but also the new anti-Xa inhibitors. Respective
      calibration curves are an indispensable condition to provide the clinician with
      valuable results. On the other hand this implies that the laboratory knows which
      anticoagulant is given to the patient. This is an example among others that
      clinical aspects are important to know for proper interpretation of the results
      of coagulation testing. Other examples are e. g. bleeding disorders, actual
      bleeding status or thromboembolic events. Several cases are discussed which
      exemplify possible pitfalls in the interpretation of coagulation testing. 

PMID- 23876751
TI  - [Pitfalls and challenges of the preanalytical phase in hematology].
AB  - In the last few decades we have seen a significant decrease in the rates of
      analytical errors in clinical laboratories. The test performances have improved,
      new parameters have been introduced, as well as internal and external quality
      controls have been used for the monitoring of accuracy. Currently available
      evidence demonstrates that the pre- and post-analytical steps show higher error
      rates (up to 70 % of all errors) than the analytical phase. Recognition of the
      weak points of the preanalytical phase and search for appropriate solutions in
      case of discrepancies will finally help to lead to the correct therapeutic
      strategy. In order to avoid problems in the preanaytical phase in hematology it
      is very important to consider some essential issues. The patients must be
      identified in appropriate form, the blood collection for the requested tests must
      be made using the appropriate tubes in the specified sequence and the samples
      must be transported to the lab at the right temperature and on time to be
      analysed. In case of special tests additional information for the lab is very
      important for the interpretation of the results. In case of unexpected results
      the lab should contact the responsible physician in order to look for an adequate
      explanation for the abnormal findings. With help of several cases of the daily
      haematology routine we want to point out some preanalytical problems. 

PMID- 23876752
TI  - [Pitfalls in the interpretation of laboratory parameters-electrolytes, urea,
      creatinine].
AB  - When it comes to interpret parameters of electrolyte balance and kidney function,
      it is important to keep pathophysiology and the theory on reference intervals in
      mind. Hyponatremia is most often caused by excess water. A low sodium
      concentration in urine should prompt a clinical evaluation of volume status. In
      case of suspected acute kidney failure, fractionated sodium excretion and
      fractionated urea excretion are able to provide insights on prerenal or renal
      origin of the disorder. Disruption in potassium homoeostasis can occur due to
      changes in supply or renal elimination as well as due to changes in the potassium
      balance between the extra- and intracellular compartments. The transtubular
      potassium gradient can help in the differential diagnosis of hyperkalemia.
      Evaluation of kidney function should begin with determination of serum
      creatinine, accompanied by an estimate of the glomerular filtration rate, as
      calculated by the CKD-EPI equation. As a consequence of non-renal determinants of
      serum creatinine, this equation has been shown to overestimate true GFR in
      elderly and hospitalized patients. This can result in overdosing of renally
      cleared drugs. Clearance determinations can be of use in this context. 

PMID- 23876753
TI  - [Evaluation of elevated liver values].
AB  - Blood analysis for the purpose of monitoring liver enzymes in the serum is a
      frequent laboratory examination in everyday clinical practice. Liver values are
      determined not only in the context of specific liver diseases, but often for the
      clarification of an unexplained illness, and sometimes in asymptomatic patients
      as part of a check-up. An evidenced based work-up of abnormal liver values is not
      easy to perform as there are no controlled clinical trials, on which we can rely
      for the rational use of further investigations. In the first introductory section
      of this article we will discuss possible algorithms used for the investigation of
      elevated liver tests, in the second section, four case reports from daily
      practice illustrate possible causes for elevated liver enzymes. 

PMID- 23876754
TI  - [Fallacies in arterial blood gas interpretation].
AB  - The arterial blood gas analysis (ABGA) is a valuable diagnostic tool in daily
      clinical practice. It yields information about oxygenation, ventilation and acid
      base status. ABGAs should always be interpreted within a clinical context. If a
      result is absolutely not compatible with a clinical situation, the probe should
      be repeated or prompt further differential diagnoses. A probe should be free of
      air bubbles and be rapidly proceeded in the laboratory. Body temperature and
      fraction of inspired oxygen are mandatory prerequisites for adequate
      interpretation. With CO-oximetry, not only oxygenated hemoglobin but also
      carboxihemoglobin and met-hemoglobin content can be measured in the case of a
      suspected intoxication. For the assessment of ventilation, PaCO2 must be
      interpreted in the context of PaO2, as already a "normal value" of PaCO2 may
      indicate severe ventilator failure in a patient with hypoxemia. A normal pH does
      not exclude acid-base disorders, PaCO2 and bicarbonate must also be taken into
      account. When FIO2 is changed, steady state conditions must be awaited before a
      next control especially in the case of ventilation-perfusion mismatch, e. g. in
      COPD, pneumonia, pulmonary embolism. In a hypoxic state, immediate application of
      oxygen is warranted, in hypercapnia, ventilation should be increased. In acid
      base disorders, treatment of the underlying disease is most often conducive. 

PMID- 23876755
TI  - [Laboratory investigation of endocrine function - interpretation of results and
      pitfalls].
AB  - Endocrine disorders are common in internal medicine. Diagnosis of endocrine
      diseases are usually based on patient history, clinical assessment and laboratory
      investigations. Thereby, biochemical analyses are used to confirm clinical
      diagnosis, to assess the need for treatment and to monitor disease progression,
      in particular to ascertain treatment efficacy. This article will focus on
      frequently used laboratory investigations for endocrine diseases such as
      diabetes, thyroid dysfunction, male hypogonadism and adrenal insufficiency. In
      particular, pre-analytical and analytical variability of biochemical measures as
      well as its significance in clinical practice will be discussed. 

PMID- 23876756
TI  - [Sense and nonsense of toxicological analyses in the daily clinical routine].
AB  - Screening tests for drugs of abuse are regularly used in the clinical routine.
      These tests identify the targeted substances very differently if tests from
      different manufacturers are used and sometimes also react positive after the
      intake of drugs which are not intended to be detected. Therefore, implausible
      results have to be questioned. A test result can be falsely negative, if a
      patient has taken a compound which is not detected by the antibody used in the
      test system. Chromatographic confirmation and screening assays are more laborious
      to perform and more demanding for the interpretation and are therefore only
      offered by several specialized clinical laboratories. However, their specificity
      is excellent and many different compounds can be detected depending on the number
      of compounds which are part of the mass spectra library used. If the clinical
      evaluation results in the differential diagnosis of an acute intoxication,
      screening tests for drugs of abuse can help to identify a single compound or a
      group of substances. The clinical picture, however, can usually not been
      explained by a qualitative test result. In addition, there are no published data
      demonstrating that these tests meaningfully influence triage, treatment,
      diagnosis or further therapy of a poisoned patient. The quantitative
      determination of specific compounds in the blood allows for example an appraisal
      of the prognosis and helps to indicate a specific therapy after intake of
      acetaminophen or methanol. New designer drugs can not at all be detected by the
      classic screening tests for drugs of abuse. The have to be identified by
      chromatographic methods. 

PMID- 23876757
TI  - In vivo anti-cancer efficacy of magnetite nanocrystal--based system using
      locoregional hyperthermia combined with 5-fluorouracil chemotherapy.
AB  - We present an approach for synchronizing hyperthermia and thermal-responsive
      local drug release. The targeting probe has a magnetite nanocrystal (Fe3O4@PSMA)
      core and a polynucleotide shell that carries 5-fluorouracil (5-FU) and anti-human
      epidermal growth factor receptor 2 (anti-HER2) antibody for cancer cell-specific
      targeting. The targeting nanocrystals play as an important role to relay the
      externally delivered radiofrequency energy for tumor hyperthermia. Locoregional
      heat then triggers a drug release from the oligonucleotide carrier as it directly
      damages tumor cells. Cell viability assays and pathological examinations show
      that this synchronization is significantly more efficacious in both in vitro and
      in vivo models than hyperthermia or chemotherapy alone. Prominent tumor remission
      in vivo was achieved through radiofrequency synchronization of hyperthermia and
      chemotherapy after the nanoparticle had been intravenously injected.

PMID- 23876758
TI  - Albumin-based nanoconjugates for targeted delivery of therapeutic
      oligonucleotides.
AB  - Nanoparticle-based delivery has become an important strategy to advance siRNA and
      antisense oligonucleotides into clinical reality. However, limited
      biodistribution of nanoparticles and the toxicity of some nanocarriers restrict
      the wider application of this strategy. To address these issues we aimed to
      construct oligonucleotide delivery systems which are non-cytotoxic and smaller
      than typical nanoparticles. Thus, a morpholino oligonucleotide was conjugated to
      a tumor-targeting RGD peptide, and then, multiple RGD-oligo conjugates were
      linked to a single molecule of human serum albumin via a reductively responsive
      linkage. The resultant nanoconjugates showed uniform and monodispersed size
      distribution with a diameter of 13 nm. A single nanoconjugate molecule contains
      15 oligonucleotides as well as 15 targeting ligands on the surface of albumin.
      The nanoparticle demonstrated 61-fold enhancement in receptor-specific cellular
      delivery of oligonucleotides in integrin-expressing tumor cells compared to the
      non-targeted control nanoconjugates and were able to robustly enhance functional
      activity of the oligonucleotide at low nanomolar concentrations without causing
      cytotoxicity. Due to their small size, the targeted nanoconjugates could
      penetrate deeply and distribute throughout 3-D tumor spheroids, whereas the
      conventional nanoparticles with sizes over 300 nm could only deliver to the cells
      on the surface of the tumor spheroids. As a result of their greater cellular
      delivery, smaller size, and lack of cytotoxicity compared to conventional
      nanoparticles, the multivalent nanoconjugates may provide an effective tool for
      targeting oligonucleotides to tumors and other diseased tissues.

PMID- 23876759
TI  - Mixed matrix hollow fiber membranes for removal of protein-bound toxins from
      human plasma.
AB  - In end stage renal disease (ESRD) waste solutes accumulate in body fluid. Removal
      of protein bound solutes using conventional renal replacement therapies is
      currently very poor while their accumulation is associated with adverse outcomes
      in ESRD. Here we investigate the application of a hollow fiber mixed matrix
      membrane (MMM) for removal of these toxins. The MMM hollow fiber consists of
      porous macro-void free polymeric inner membrane layer well attached to the
      activated carbon containing outer MMM layer. The new membranes have permeation
      properties in the ultrafiltration range. Under static conditions, they adsorb 57%
      p-cresylsulfate, 82% indoxyl sulfate and 94% of hippuric acid from spiked human
      plasma in 4 h. Under dynamic conditions, they adsorb on average 2.27 mg PCS/g
      membrane and 3.58 mg IS/g membrane in 4 h in diffusion experiments and 2.68 mg/g
      membrane PCS and 12.85 mg/g membrane IS in convection experiments. Based on the
      dynamic experiments we estimate that our membranes would suffice to remove the
      daily production of these protein bound solutes.

PMID- 23876760
TI  - Anti-leukemia activity of PVP-coated silver nanoparticles via generation of
      reactive oxygen species and release of silver ions.
AB  - Silver nanoparticles (AgNPs) have anti-cancer effect. However, whether and how
      these particles could inhibit the growth of acute myeloid leukemia (AML) cells is
      unclear. In the present study, we prepared AgNPs with various sizes and
      investigated their cytotoxic effect on AML cells. We found that AgNPs could
      inhibit the viability of AML cells including the isolates from AML patients.
      AgNPs caused the production of reactive oxygen species (ROS), losses of
      mitochondrial membrane potential (MMP), DNA damage and apoptosis. Both vitamin C
      (Vit C) and N-acetyl-L-cysteine (NAC) could completely reverse the generation of
      ROS upon AgNPs, however only NAC but not Vit C could protect the cells from
      losses of MMP, DNA damage and apoptosis thoroughly. Similar results were obtained
      when cells were treated with silver ions alone. As NAC was not only an
      antioxidant to scavenge ROS but also a silver ion chelator, these data supported
      the model that both generation of ROS and release of silver ions played critical
      roles in the AgNPs-induced cytotoxic effect against AML cells. Taken together,
      this work elucidated the cytotoxic effect of AgNPs on AML cells and their
      underlying mechanism and might have significant impact on AML treatment.

PMID- 23876761
TI  - The combined influence of substrate elasticity and surface-grafted molecules on
      the ex vivo expansion of hematopoietic stem and progenitor cells.
AB  - Umbilical cord blood (UCB) is an attractive source of hematopoietic stem and
      progenitor cells (HSPCs) for transplantation. However, the low number of HSPCs
      from a single UCB donor limits the direct transplantation of UCB to patients.
      Because little is known about the effects of the physical microenvironment on
      HSPC expansion, we investigated the ex vivo expansion of HSPCs cultured on
      biomaterials with different elasticities and grafted with different nanosegments.
      Polyvinylalcohol-co-itaconic acid (PVA-IA)-coated dishes with different
      stiffnesses ranging from a 3.7 kPa to 30.4 kPa storage modulus were used.
      Fibronectin or an oligopeptide (CS1, EILDVPST) was grafted onto the PVA-IA
      substrates. High ex vivo fold expansion of HSPCs was observed in the PVA-IA
      dishes grafted with fibronectin or CS1, which displayed an intermediate stiffness
      ranging from 12.2 kPa to 30.4 kPa. The fold expansion was more than 1.4 times
      higher than that cultured in tissue culture polystyrene dishes (TCPS, 12 GPa).
      Furthermore, HSPCs cultured in fibronectin or CS1-grafted PVA-IA-coated dishes
      with a stiffness of 12.2-30.4 kPa generated more pluripotent colony-forming units
      (CFU-GM and CFU-GEMM) than those in TCPS dishes. This result indicates that both
      the physical and biological properties of biomaterials affect the ex vivo
      expansion of HSPCs.

PMID- 23876762
TI  - Does the neobladder filling modulate soleus H reflex?

PMID- 23876763
TI  - Study of LZ-word distribution and its application for sequence comparison.
AB  - Lempel-Ziv complexity has been widely used for sequence comparison and achieved
      promising results, but until now components' distribution in exhaustive history
      has not been studied. This paper investigated the whole distribution of LZ-words
      and presented a novel statistical method for sequence comparison. With the
      components' length in mind, we revised Lempel-Ziv complexity and obtained various
      sets of LZ-words. Instead of calculating the LZ-words' contents, we defined a
      series of set operations on LZ-word set to compare biological sequences. In order
      to assess the effectiveness of the proposed method, we performed two sets of
      experiments and compared it with alignment-based methods. 

PMID- 23876764
TI  - Local behavioral rules sustain the cell allocation pattern in the combs of honey
      bee colonies (Apis mellifera).
AB  - In the beeswax combs of honey bees, the cells of brood, pollen, and honey have a
      consistent spatial pattern that is sustained throughout the life of a colony.
      This spatial pattern is believed to emerge from simple behavioral rules that
      specify how the queen moves, where foragers deposit honey/pollen and how
      honey/pollen is consumed from cells. Prior work has shown that a set of such
      rules can explain the formation of the allocation pattern starting from an empty
      comb. We show that these rules cannot maintain the pattern once the brood start
      to vacate their cells, and we propose new, biologically realistic rules that
      better sustain the observed allocation pattern. We analyze the three resulting
      models by performing hundreds of simulation runs over many gestational periods
      and a wide range of parameter values. We develop new metrics for pattern
      assessment and employ them in analyzing pattern retention over each simulation
      run. Applied to our simulation results, these metrics show alteration of an
      accepted model for honey/pollen consumption based on local information can
      stabilize the cell allocation pattern over time. We also show that adding global
      information, by biasing the queen's movements towards the center of the comb,
      expands the parameter regime over which pattern retention occurs. 

PMID- 23876765
TI  - Ripped, shucked, and scattered.

PMID- 23876766
TI  - Protein adsorption to poly(ethylenimine)-modified Sepharose FF: I. a critical
      ionic capacity for drastically enhanced capacity and uptake kinetics.
AB  - To explore the details of protein uptake to polymer-grafted ion exchangers,
      Sepharose FF was modified with poly(ethylenimine) (PEI) to prepare anion
      exchanger of 10 different ionic capacities (ICs, 100-1220mmol/L). Adsorption
      equilibria and kinetics of bovine serum albumin (BSA) were then studied. It is
      found that ionic capacity, i.e., the coupling density of PEI, had significant
      effect on both adsorption capacity (qm) and effective protein diffusivity (De).
      With increasing ionic capacity, the qm value increased rapidly at IC<260mmol/L
      and then increased slowly till reaching a plateau at IC=600mmol/L. In the IC
      range of 100-600mmol/L, however, the De values kept at a low level (De/D0<0.07);
      it first decreased from 0.05+/-0.01 at IC=100mmol/L to 0.01+/-0.01 at
      IC=260mmol/L and then increased to 0.06+/-0.01 at IC=600mmol/L. Thereafter, sharp
      increases of the qm and De values [36% (from 201 to 273mg/mL) and 670% (from
      0.06+/-0.01 to 0.49+/-0.04), respectively] were observed in the narrow range of
      IC from 600 to 740mmol/L. Finally, at IC>740mmol/L, the qm value decreased
      significantly while the De value increased moderately with increasing the IC. The
      results indicate that PEI chains played an important role in protein adsorption
      and transport. In brief, there was a critical IC (cIC) or PEI chain density,
      above which protein adsorption and transport behaviors changed drastically. The
      cIC was identified to be about 600mmol/L. Estimation of PEI grafting-layer
      thickness suggests that PEI chains formed an extended three-dimensional grafting
      layer at IC>cIC, which provided high flexibility as well as accessibility of the
      chains for protein binding. Therefore, at IC>cIC, the adjacent PEI chains became
      close and flexible enough, leading to facilitated transport of adsorbed protein
      molecules by the interactions of neighboring chains mediated by the bound
      molecules. It is regarded as "chain delivery" effect. At the same time, improved
      accessibility of binding sites led the significant increase of binding capacity.
      The decrease of qm value at IC>740mmol/L is considered due to the decrease of
      effective porosity. The research has thus provided new insight into protein
      adsorption and transport in polymer-grafted ion-exchange media. 

PMID- 23876767
TI  - Needle-type extraction device for the purge and trap analysis of 23 volatile
      organic compounds in tap water.
AB  - We developed a rapid determination technique for trace volatile organic compounds
      (VOCs) in tap water by introducing a novel needle-type extraction device coupled
      to a purge-and-trap method. To extract a wide range of VOCs, a new extraction
      needle containing particles of divinylbenzene and activated carbon was developed
      in this study. During the active sampling of the headspace gas in a glass vial by
      the extraction needle, pure N2 gas was used for purging the aqueous sample. After
      the optimization of several experimental parameters, such as the addition of the
      salt and conditions of dry purging and desorption, the extraction performance of
      the device and method was evaluated for 23 VOCs that are typically found in tap
      water samples. The quantification limits of the method were 0.6 MUg/L for 1,1
      dichloroethylene and less than 0.5 MUg/L for other VOCs, with good repeatability
      being confirmed for all the target compounds. Taking advantage of the excellent
      recovery of VOCs, the determination of VOCs in real tap water samples was carried
      out successfully. Because the developed method does not require sample heating
      and/or cryogenic focusing, simple and rapid analyses can be performed along with
      satisfactory sensitivity for typical tap water samples.

PMID- 23876768
TI  - Reversed phase ion-pairing chromatography of an oligolysine mixture in different
      mobile phases: effort of searching critical chromatography conditions.
AB  - Our earlier study [J. Chromatogr. A 1218 (2011) 7765] on separation of an
      oligolysine mixture consisting of chains with 2-8 lysine residues (number of
      lysine residues, dp=2-8) by ion-pairing reversed-phase chromatography using
      heptafluorobutyric acid (HFBA) as an ion pairing reagent at fixed mobile phase
      acetonitrile (ACN) content was extended to isocratic elution conditions with
      different ACN percentages. The present work explored how manipulating the mobile
      phase HFBA concentration ([HFBA]) and %-ACN content influences separations of the
      oligolysine mixture. The closed pairing model was used to analyze variation of
      the retention factor as a function of [HFBA]. The partition coefficient of the
      paired peptide decreased with increasing %-ACN. Pairing of HFBA to oligolysine
      was cooperative, and the effect increased when %-ACN in the mobile phase was
      lowered. A plot of the partition coefficient as a function of %-ACN for
      oligolysines varying in dp converged at one ACN content, indicating a critical
      condition in which components of different dp co-elute. 

PMID- 23876769
TI  - Application of statistical experimental design to the optimisation of
      microextraction by packed sorbent for the analysis of nonsteroidal anti
      inflammatory drugs in human urine by ultra-high pressure liquid chromatography.
AB  - A new approach based on microextraction by packed sorbent (MEPS) and a reversed
      phase ultra-high pressure liquid chromatography (UHPLC) method was developed and
      validated for the determination and quantification of nonsteroidal anti
      inflammatory drugs (NSAIDs) (acetylsalicylic acid, ketoprofen, diclofenac,
      naproxen and ibuprofen) in human urine. The important factors that could
      influence the extraction were previously screened using the Plackett-Burman
      design approach. The optimal MEPS extraction conditions were obtained using C18
      phase as a sorbent, small sample volume (20MUL) and a short time period
      (approximately 5min) for the entire sample preparation step. The analytes were
      separated on a core-shell column (Poroshell 120 EC-C18; 100mm*3.0mm; 2.7MUm)
      using a binary mobile phase composed of aqueous 0.1% trifluoroacetic acid and
      acetonitrile in the gradient elution mode (4.5min of analysis time). The
      analytical method was fully validated based on linearity, limits of detection
      (LOD), limits of quantification (LOQ), inter- and intra-day precision and
      accuracy, and extraction yield. Under optimised conditions, excellent linearity
      (R(2)>0.9991), limits of detection (1.07-16.2ngmL(-1)) and precision (0.503-9.15%
      RSD) were observed for the target drugs. The average absolute recoveries of the
      analysed compounds extracted from the urine samples were 89.4-107%. The proposed
      method was also applied to the analysis of NSAIDs in human urine. The new
      approach offers an attractive alternative for the analysis of selected drugs from
      urine samples, providing several advantages including fewer sample preparation
      steps, faster sample throughput and ease of performance compared to traditional
      methodologies. 

PMID- 23876770
TI  - Meta-analysis of randomized controlled trials comparing outcomes for stapled
      hemorrhoidopexy versus LigaSure hemorrhoidectomy for symptomatic hemorrhoids in
      adults.
AB  - This purpose of the meta-analysis was to compare treatment outcomes for adult
      patients with symptomatic hemorrhoids treated by stapled hemorrhoidopexy or
      LigaSure hemorrhoidectomy. A search of public medical databases was made to
      identify randomized controlled trials (RCTs) comparing stapled hemorrhoidopexy
      (SH) with LigaSure hemorrhoidectomy (LH) for the treatment of adult patients with
      symptomatic grade 3 and grade 4 hemorrhoids. Postoperative pain as measured using
      a visual analog scale was the primary outcome, and rate of recurrent prolapse and
      postoperative bleeding were secondary outcome measures. Four RCTs were identified
      that met the inclusion criteria. Data for the pooled outcomes were analyzed using
      odds ratio (OR) analysis. None of the studies in the analysis indicated a
      significant difference between SH and LH for the outcomes VAS pain score,
      recurrence rate, or postoperative bleeding. Pooled analysis revealed a
      significant OR in favor of the SH method for recurrent prolapse (OR = 5.529, P =
      0.016) for up to 2 years after surgery. No significant differences between the
      two methods were identified for VAS pain scores (OR = -1.060, P = 0.149) or
      postoperative bleeding OR = 1.188, P = 0.871). Pooled analysis of RCT results
      comparing SH to LH for symptomatic hemorrhoids revealed a significantly greater
      incidence of recurrent prolapse for SH. The two techniques were associated with
      similar levels of postoperative pain and postoperative bleeding.

PMID- 23876771
TI  - Epigenetics(-omics) takes center stage.

PMID- 23876772
TI  - Epigenetic regulation of serotonin transporter in psychiatric disorders.

PMID- 23876773
TI  - DNA methylation, behavior and early life adversity.
AB  - The impact of early physical and social environments on life-long phenotypes is
      well known. Moreover, we have documented evidence for gene-environment
      interactions where identical gene variants are associated with different
      phenotypes that are dependent on early life adversity. What are the mechanisms
      that embed these early life experiences in the genome? DNA methylation is an
      enzymatically-catalyzed modification of DNA that serves as a mechanism by which
      similar sequences acquire cell type identity during cellular differentiation and
      embryogenesis in the same individual. The hypothesis that will be discussed here
      proposes that the same mechanism confers environmental-exposure specific identity
      upon DNA providing a mechanism for embedding environmental experiences in the
      genome, thus affecting long-term phenotypes. Particularly important is the
      environment early in life including both the prenatal and postnatal social
      environments. 

PMID- 23876774
TI  - The epigenetic switches for neural development and psychiatric disorders.
AB  - The most remarkable feature of the nervous system is that the development and
      functions of the brain are largely reshaped by postnatal experiences, in joint
      with genetic landscapes. The nature vs. nurture argument reminds us that both
      genetic and epigenetic information is indispensable for the normal function of
      the brain. The epigenetic regulatory mechanisms in the central nervous system
      have been revealed over last a decade. Moreover, the mutations of epigenetic
      modulator genes have been shown to be implicated in neuropsychiatric disorders,
      such as autism spectrum disorders. The epigenetic study has initiated in the
      neuroscience field for a relative short period of time. In this review, we will
      summarize recent discoveries about epigenetic regulation on neural development,
      synaptic plasticity, learning and memory, as well as neuropsychiatric disorders.
      Although the comprehensive view of how epigenetic regulation contributes to the
      function of the brain is still not completed, the notion that brain, the most
      complicated organ of organisms, is profoundly shaped by epigenetic switches is
      widely accepted. 

PMID- 23876776
TI  - Histone variants in development and diseases.
AB  - Eukaryotic genomic DNA is highly packaged into chromatin by histones to fit
      inside the nucleus. Other than the bulk packaging role of canonical histones with
      an expression peak at S phase and replication-coupled deposition, different
      histone variants have evolved distinct regulatory mechanisms for their
      expression, deposition and functional implications. The diversity of histone
      variants results in structural plasticity of chromatin and highlights
      functionally distinct chromosomal domain, which plays critical roles in
      development from a fertilized egg into a complex organism, as well as in aging
      and diseases. However, the mechanisms of this fundamental process are poorly
      understood so far. It is of particular interest to investigate how the variants
      are incorporated into chromatin and mark specific chromatin states to regulate
      gene expression, and how they are involved in development and diseases. In this
      review, we focus on recent progress in studies of epigenetic regulation of three
      extensively investigated variants including H2A.Z, macroH2A and H3.3, and their
      functional implications in development and diseases. 

PMID- 23876775
TI  - The class III histone deacetylase sirtuin 1 in immune suppression and its
      therapeutic potential in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic debilitating disease of the joints. Both
      the innate and adaptive immune responses participate in the development and
      progression of RA. While several therapeutic reagents, such as TNF-alpha
      agonists, have been successfully developed for the clinical use in the treatment
      of RA, more than half of the patients do not respond to anti-TNF therapy.
      Therefore, new therapeutic reagents are needed. Recent studies have shown that
      sirtuin 1 (Sirt1), a nicotinamide adenine dinucleotide (NAD)-dependent histone
      deacetylase, is a critical negative regulator of both the innate and adaptive
      immune response in mice, and its altered functions are likely to be involved in
      autoimmune diseases. Small molecules that modulate Sirt1 functions are potential
      therapeutic reagents for autoimmune inflammatory diseases. This review highlights
      the role of Sirt1 in immune regulation and RA. 

PMID- 23876777
TI  - Regulatory roles of metabolites in cell signaling networks.
AB  - Mounting evidence suggests that cellular metabolites, in addition to being
      sources of fuel and macromolecular substrates, are actively involved in signaling
      and epigenetic regulation. Many metabolites, such as cyclic AMP, which regulates
      phosphorylation/dephosphorylation, have been identified to modulate DNA and
      histone methylation and protein stability. Metabolite-driven cellular regulation
      occurs through two distinct mechanisms: proteins allosterically bind or serve as
      substrates for protein signaling pathways, and metabolites covalently modify
      proteins to regulate their functions. Such novel protein metabolites include
      fumarate, succinyl-CoA, propionyl-CoA, butyryl-CoA and crontonyl-CoA. Other
      metabolites, including alpha-ketoglutarate, succinate and fumarate, regulate
      epigenetic processes and cell signaling via protein binding. Here, we summarize
      recent progress in metabolite-derived post-translational protein modification and
      metabolite-binding associated signaling regulation. Uncovering metabolites
      upstream of cell signaling and epigenetic networks permits the linkage of
      metabolic disorders and human diseases, and suggests that metabolite modulation
      may be a strategy for innovative therapeutics and disease prevention techniques. 

PMID- 23876778
TI  - Comparison of treatment outcomes with vancomycin alone versus combination therapy
      in severe Clostridium difficile infection.
AB  - BACKGROUND: The recommended treatment for severe Clostridium difficile infection
      (CDI) is oral vancomycin alone. Combination therapy with metronidazole is only
      recommended in cases complicated by shock, ileus, or toxic megacolon. However,
      patients with severe infection are often treated with combination therapy despite
      a lack of data supporting this practice. AIM: To evaluate differences in outcomes
      for patients with severe CDI treated with oral vancomycin alone versus
      combination therapy. METHODS: Medical records of 78 patients with severe CDI
      receiving either oral vancomycin alone or combination therapy for >= 72h were
      retrospectively reviewed. The primary outcome was time to clinical cure of CDI,
      defined as the first day of resolution of diarrhoea for >= 48h without
      development of a complication. Other endpoints included cure rates, complication
      rates, and recurrence rates. FINDINGS: There was no difference in the incidence
      of clinical cure between monotherapy and combination therapy (57.1% vs 65.1%, P =
      0.49). Median time to clinical cure was 7.0 days for the monotherapy group and
      8.0 days for combination therapy (P = 0.19). After adjustment for potential
      confounders, the hazard ratio of the time to clinical cure for combination
      therapy compared with monotherapy was 0.58 (P = 0.10). There was no difference in
      recurrence rate or rates of individual complications between groups; however,
      there was a significantly higher composite complication rate in the combination
      therapy group. CONCLUSION: These data suggest that there is no difference in
      treatment outcomes between monotherapy and combination therapy for severe CDI.

PMID- 23876779
TI  - Exact analytical results for ADC with oscillating diffusion sensitizing
      gradients.
AB  - The apparent diffusion coefficient (ADC) is analyzed for the case of oscillating
      diffusion sensitizing gradients. Exact analytical expressions are obtained in the
      high-frequency expansion of the ADC for an arbitrary number of oscillations N.
      These expressions are universal and valid for arbitrary system geometry. The
      validity conditions of the high-frequency expansion of ADC are obtained in the
      framework of a simple 1D model of restricted diffusion. These conditions are
      shown to be substantially different for cos- and sin-type gradients: for the cos
      type gradients, the high-frequency expansion is valid when the period of a single
      oscillation is smaller than the characteristic diffusion time, the frequency
      dependence of ADC being practically the same for any N. In contrast, for the sin
      type gradients, the high-frequency regime can be achieved only when the total
      diffusion time is smaller than the characteristic diffusion time, the frequency
      dependence of ADC being different for different N. 

PMID- 23876780
TI  - High-resolution proton CRAMPS NMR using narrowband analog filters and postponed
      data acquisition.
AB  - Proton linewidths decrease with increasing magic-angle spinning (MAS) rates.
      However, without spin dilution by deuteration, even with the fastest MAS rates
      available today, the narrowest proton linewidths are obtained by using the
      combined rotation and multiple pulse spectroscopy (CRAMPS) method. Direct
      observation under windowed CRAMPS typically introduces several tens of times more
      noise, partly because wideband analog filters (e.g. 5 MHz) must be used or
      sometimes even bypassed. Here we report that it is possible to keep using
      narrowband analog filters (about 50 kHz cutoff frequency) in CRAMPS by taking
      advantage of the time delay caused by the filters, which is inversely
      proportional to the cutoff frequency. This delay coincides with typical CRAMPS
      cycle times, enabling acquisition of the data point in the next detection window.
      The noise of such CRAMPS spectra is only about 5 times larger than MAS-only
      spectra. This new method allows CRAMPS to be performed on systems that lack
      wideline hardware (wideband filters and fast ADCs), for example, older
      spectrometers originally intended for solution NMR.

PMID- 23876781
TI  - Development of an eight-channel NMR system using RF detection coils for measuring
      spatial distributions of current density and water content in the PEM of a PEFC.
AB  - The water generation and water transport occurring in a polymer electrolyte fuel
      cell (PEFC) can be estimated from the current density generated in the PEFC, and
      the water content in the polymer electrolyte membrane (PEM). In order to measure
      the spatial distributions and time-dependent changes of current density generated
      in a PEFC and the water content in a PEM, we have developed an eight-channel
      nuclear magnetic resonance (NMR) system. To detect a NMR signal from water in a
      PEM at eight positions, eight small planar RF detection coils of 0.6 mm inside
      diameter were inserted between the PEM and the gas diffusion layer (GDL) in a
      PEFC. The local current density generated at the position of the RF detection
      coil in a PEFC can be calculated from the frequency shift of the obtained NMR
      signal due to an additional magnetic field induced by the local current density.
      In addition, the water content in a PEM at the position of the RF detection coil
      can be calculated by the amplitude of the obtained NMR signal. The time-dependent
      changes in the spatial distributions were measured at 4 s intervals when the PEFC
      was operated with supply gas under conditions of fuel gas utilization of 0.67 and
      relative humidity of the fuel gas of 70%RH. The experimental result showed that
      the spatial distributions of the local current density and the water content in
      the PEM within the PEFC both fluctuated with time.

PMID- 23876782
TI  - Longitudinal associations from neurobehavioral disinhibition to adolescent risky
      sexual behavior in boys: direct and mediated effects through moderate alcohol
      consumption.
AB  - PURPOSE: This longitudinal study tested the hypothesis that neurobehavioral
      disinhibition (ND) in childhood, mediated by alcohol use, portends risky sexual
      behavior (number of sexual partners) in midadolescence. METHODS: Participants
      were 410 adolescent boys. Neurobehavioral disinhibition was assessed at 11.3
      years of age. Frequency and quantity of alcohol use on a typical drinking
      occasion were assessed at 13.4 years of age at first follow-up, and sexual
      behavior at 16.0 years at second follow-up. RESULTS: Quantity of alcohol consumed
      on a typical drinking occasion, but not frequency of alcohol use, mediated the
      relation between ND and number of sexual partners. CONCLUSIONS: These findings
      indicate that number of sexual partners in midadolescence is predicted by
      individual differences in boys' psychological self-regulation during childhood
      and moderate alcohol consumption in early adolescence, and that ND may be a
      potential target for multi-outcome public health interventions.

PMID- 23876783
TI  - YouTube as a potential online source of information in the prevention and
      management of paediatric burn injuries.

PMID- 23876784
TI  - Is the length of time in acute burn surgery associated with poorer outcomes?
AB  - BACKGROUND: Acute wound closure surgery improves outcomes, after burn
      particularly mortality, but also imposes physiological stress on the patient. The
      duration of surgery is associated with adverse outcomes in other populations.
      This study aimed to examine if extended acute burn surgery duration was
      associated with poorer in-hospital outcomes. METHODS: This retrospective cohort
      study included adult burn patients who required a single wound closure surgery at
      Royal Perth Hospital between 2004 and 2011. Multivariable regression analyses
      were used to assess the influence of patient and injury factors on surgery
      duration and length of stay (LOS). RESULTS: Surgery duration independently
      increased LOS (incidence rate ratio [IRR]=1.004, p<0.001). This translates to a
      predicted 13% increase in LOS for a 30min increase in surgery 'knife to skin'
      time. Total body surface area (TBSA) was identified as a significant predictor of
      surgery duration (IRR=1.047, p<0.001), estimating that a 10% TBSA increase
      results in a 59% increase in surgery duration. CONCLUSION: The results show that
      surgery duration is associated with LOS after adjusting for size of burn and
      other factors. The study justifies the need to explore strategies to reduce acute
      burn surgery duration.

PMID- 23876785
TI  - Amikacin population pharmacokinetics among paediatric burn patients.
AB  - INTRODUCTION: The objectives of this study were to (1) determine the
      pharmacokinetics of amikacin among children with severe burn and (2) identify
      influential covariates. METHODS: Population-based pharmacokinetic modelling was
      performed in NONMEM 7.2 for hospitalized children who received amikacin at 10
      20mg/kg divided two, three, or four times per day as part of early empiric
      treatment of presumed burn-related sepsis. RESULTS: The analysis included data
      from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations.
      Amikacin's mean Cmax was 33.2+/-9.4MUg/mL and the mean Cmin was 3.8+/-4.6MUg/mL.
      The final covariate model estimated clearance as 5.98L/h/70kg (4.97-6.99, 95%
      CI), the volume of distribution in the central compartment as 16.7L/70kg (14.0
      19.4, 95% CI), the volume of distribution in the peripheral compartment as
      40.1L/70kg (15.0-80.4, 95% CI), and the inter-compartmental clearance as
      3.38L/h/70kg (2.44-4.32, 95% CI). In multivariate analyses, current weight
      (P<0.001) was a significant covariate, while age, sex, height, serum creatinine,
      C-reactive protein, platelet count, the extent and type of burn, and concomitant
      vancomycin administration did not influence amikacin pharmacokinetics.
      DISCUSSION: Children with burn featured elevated amikacin clearance when compared
      to healthy adult volunteers. However, peak amikacin concentrations are comparable
      to those attained in other critically-ill children, suggesting that elevated
      amikacin clearance may not result in sub-therapeutic antibacterial effects. In
      this study, we found that amikacin displays two-compartment pharmacokinetics,
      with weight exerting a strong effect upon amikacin clearance. Further
      pharmacodynamic studies are needed to establish the optimal dosing regimen for
      amikacin in paediatric burn patients.

PMID- 23876786
TI  - BDNF val66met modulates the association between childhood trauma, cognitive and
      brain abnormalities in psychoses.
AB  - OBJECTIVE: Brain derived neurotrophic factor (BDNF) is important for brain
      development and plasticity, and here we tested if the functional BDNF val66met
      variant modulates the association between high levels of childhood abuse,
      cognitive function, and brain abnormalities in psychoses. METHOD: 249 patients
      with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were
      consecutively recruited to the TOP research study (mean+/-age: 30.7+/-10.9;
      gender: 49% males). History of childhood trauma was obtained using the Childhood
      Trauma Questionnaire. Cognitive function was assessed through a standardized
      neuropsychological test battery. BDNF val66met was genotyped using standardized
      procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia
      spectrum disorder or bipolar disorder (mean+/-age: 32.67+/-10.85; 49% males) had
      data on sMRI. RESULTS: Carriers of the Methionine (met) allele exposed to high
      level of childhood abuse demonstrated significantly poorer cognitive functioning
      compared to homozygotic Valine (val/val) carriers. Taking in consideration
      multiple testing, using a more conservative p value, this was still shown for
      physical abuse and emotional abuse, as well as a trend level for sexual abuse.
      Further, met carriers exposed to high level of childhood sexual abuse showed
      reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left
      lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively).
      Our findings were independent of age, gender, diagnosis and intracranial volume.
      CONCLUSION: Our data demonstrate that in patients with psychoses, met carriers of
      the BDNF val66met with high level of childhood abuse have more cognitive and
      brain abnormalities than all other groups.

PMID- 23876787
TI  - Morphometric brain characterization of refractory obsessive-compulsive disorder:
      diffeomorphic anatomic registration using exponentiated Lie algebra.
AB  - BACKGROUND: Few studies have used neuroimaging to characterize treatment
      refractory obsessive-compulsive disorder (OCD). This study sought to explore gray
      matter structure in patients with treatment-refractory OCD and compare it with
      that of healthy controls. METHODS: A total of 18 subjects with treatment
      refractory OCD and 26 healthy volunteers were analyzed by MRI using a 3.0-T
      scanner and voxel-based morphometry (VBM). Diffeomorphic anatomical registration
      using exponentiated Lie algebra (DARTEL) was used to identify structural changes
      in gray matter associated with treatment-refractory OCD. A partial correlation
      model was used to analyze whether morphometric changes were associated with Yale
      Brown Obsessive-Compulsive Scale scores and illness duration. RESULTS: Gray
      matter volume did not differ significantly between the two groups. Treatment
      refractory OCD patients showed significantly lower gray matter density than
      healthy subjects in the left posterior cingulate cortex (PCC) and mediodorsal
      thalamus (MD) and significantly higher gray matter density in the left dorsal
      striatum (putamen). These changes did not correlate with symptom severity or
      illness duration. CONCLUSIONS: Our findings provide new evidence of deficits in
      gray matter density in treatment-refractory OCD patients. These patients may show
      characteristic density abnormalities in the left PCC, MD and dorsal striatum
      (putamen), which should be verified in longitudinal studies.

PMID- 23876788
TI  - Antidepressant-like effects of curcumin in chronic mild stress of rats:
      involvement of its anti-inflammatory action.
AB  - Mounting evidence suggests that inflammation may contribute to the
      pathophysiology of depression. Curcumin, a polyphenol extracted from the plant
      Curcuma longa, exhibits a number of pharmacological properties, including potent
      anti-inflammatory action. Hence, the current study aimed to explore the
      immunomodulatory effects of curcumin in an animal model of chronic mild stress
      (CMS). Rats were subjected to CMS protocol for a period of 21 days to induce
      depressive-like behavior. The body weight, sucrose preference and locomotor
      activity were evaluated. Both RT-PCR and ELISA were used to determine the
      expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in
      the prefrontal cortex and hippocampus. Modulation of nuclear factor-kappaB (NF
      kappaB) activation was assessed by western blotting. Chronic treatment with
      curcumin significantly reversed the CMS-induced behavioral abnormalities (reduced
      sucrose preference and decreased locomotor activity) in stressed rats.
      Additionally, curcumin effectively inhibited cytokine gene expression at both the
      mRNA and the protein level and reduced the activation of NF-kappaB. The study
      revealed that curcumin exerted antidepressant-like effects in CMS rats, partially
      due to its anti-inflammatory aptitude.

PMID- 23876789
TI  - Reward/punishment sensitivities among internet addicts: Implications for their
      addictive behaviors.
AB  - Internet addiction disorder (IAD) has raised widespread public health concerns.
      In this study, we used a gambling task to simulate extreme win/lose situations to
      find the reward/punishment sensitivities after continuous wins and losses. FMRI
      data were collected from 16 IAD subjects (21.4+/-3.1years) and 15 healthy
      controls (HC, 22.1+/-3.6years). Group comparisons showed higher superior frontal
      gyrus activations after continuous wins for IAD subjects than for HC. The brain
      activities in IAD subjects were not disturbed by their losses. In addition, IAD
      participants showed decreased posterior cingulate activation compared to HC after
      continuous losses. These results indicated that IAD participants showed
      preference to win while neglecting their losses. Therefore they engaged less
      executive endeavor to control their frustration after continuous losses. Taken
      together, we concluded that IAD subjects showed enhanced sensitivity to win and
      decreased sensitivity to lose. This can help us understand why IAD subjects
      continue playing online even after noticing the severe negative consequences of
      their behaviors. 

PMID- 23876790
TI  - Molecular origins of binding affinity: seeking the Archimedean point.
AB  - Connecting three dimensional structure and affinity is analogous to seeking the
      'Archimedean point', a vantage point from where any observer can quantitatively
      perceive the subject of inquiry. Here we review current knowledge and challenges
      that lie ahead of us in the quest for this Archimedean point. We argue that
      current models are limited in reproducing measured data because molecular
      description of binding affinity must expand beyond the interfacial contribution
      and also incorporate effects stemming from conformational changes/dynamics and
      long-range interactions. Fortunately, explicit modeling of various kinetic
      schemes underlying biomolecular recognition and confined systems that reflect in
      vivo interactions are coming within reach. This quest will hopefully lead to an
      accurate biophysical interpretation of binding affinity that would allow
      unprecedented understanding of the molecular basis of life through unraveling the
      why's of interaction networks. 

PMID- 23876791
TI  - Reduction of biological agent dose in rheumatic diseases: descriptive analysis of
      153 patients in clinical practice conditions.
AB  - OBJECTIVE: To analyze the frequency and characteristics of dose reduction of
      biological agents in a cohort of patients with chronic arthritis, in clinical
      practice conditions in a tertiary level hospital. MATERIAL AND METHODS:
      Descriptive, cross-sectional study, which included all patients, followed
      consecutively during 6 months (June 2011-November 2011), by one investigator,
      with patients who at least have received one dose of biological agents in 2011.
      RESULTS: We included 153 patients: Rheumatoid arthritis (RA) (n=82), ankylosing
      spondylitis (n=29), psoriatic arthritis (n=20), and miscellaneous group (n=22).
      Mean disease duration was 14.9+/-7.7 years. At the time of analysis, 70 patients
      (45.7%) were receiving low doses of biological therapy (50% in miscellaneous
      group group, 50% in psoriatic arthritis, 48.2% in ankylosing spondylitis, and
      42.6% in RA). Mean time of dosage reduction was 17.4+/-17.5 months. The most
      common biological agents used in low dose were: etanercept, adalimumab and
      tocilizumab; 57.6%, 54.9% and 40% respectively, in patients with a reduced dose
      of biological therapy. The patients at low dose of biological therapy compared
      with standard dose, had similar mean disease duration, but received significantly
      less DMARDs, glucocorticoids and NSAIDs, and similar biological agent duration.
      RA patients with reduced biological treatment, at the time of analysis, had
      higher remission rates versus patients receiving a standard dose (82.9% vs 34%,
      p<0.0001). The medical decision at the time of analysis was to maintain low
      dosage biological treatment in almost all patients. CONCLUSION: In our clinical
      practice, 45.7% of our chronic arthritis patients receive low dose of biological
      therapy, after achieving remission or low activity at standard doses, maintaining
      a good control of the disease.

PMID- 23876792
TI  - Macrolide resistance of Mycoplasma pneumoniae, South Korea, 2000-2011.
AB  - In Korea, Mycoplasma pneumoniae was detected in 255/2,089 respiratory specimens
      collected during 2000-2011; 80 isolates carried 23S rRNA gene mutations, and
      69/123 culture-positive samples with the mutation were resistant to 5 macrolides.
      During 2000-2011, prevalence of the mutation increased substantially. These
      findings have critical implications for the treatment of children with mycoplasma
      pneumonia. 

PMID- 23876793
TI  - Filopodia as sensors.
AB  - Filopodia are sensors on both excitable and non-excitable cells. The sensing
      function is well documented in neurons and blood vessels of adult animals and is
      obvious during dorsal closure in embryonic development. Nerve cells extend
      neurites in a bidirectional fashion with growth cones at the tips where filopodia
      are concentrated. Their sensing of environmental cues underpins the axon's
      ability to "guide," bypassing non-target cells and moving toward the target to be
      innervated. This review focuses on the role of filopodia structure and dynamics
      in the detection of environmental cues, including both the extracellular matrix
      (ECM) and the surfaces of neighboring cells. Other protrusions including the
      stereocilia of the inner ear and epididymus, the invertebrate Type I
      mechanosensors, and the elongated processes connecting osteocytes, share certain
      principles of organization with the filopodia. Actin bundles, which may be inside
      or outside of the excitable cell, function to transduce stress from physical
      perturbations into ion signals. There are different ways of detecting such
      perturbations. Osteocyte processes contain an actin core and are physically
      anchored on an extracellular structure by integrins. Some Type I mechanosensors
      have bridge proteins that anchor microtubules to the membrane, but bundles of
      actin in accessory cells exert stress on this complex. Hair cells of the inner
      ear rely on attachments between the actin-based protrusions to activate ion
      channels, which then transduce signals to afferent neurons. In adherent
      filopodia, the focal contacts (FCs) integrated with ECM proteins through
      integrins may regulate integrin-coupled ion channels to achieve signal
      transduction. Issues that are not understood include the role of Ca(2+) influx in
      filopodia dynamics and how integrins coordinate or gate signals arising from
      perturbation of channels by environmental cues. 

PMID- 23876794
TI  - Regulation of Btg2(/TIS21/PC3) expression via reactive oxygen species-protein
      kinase C-NuFkappaBeta pathway under stress conditions.
AB  - Human B-cell translocation gene 2 (BTG2), an ortholog of mouse TIS21 (12-O
      tetradecanoyl phorbol-13-acetate inducible sequence 21) and rat PC3
      (Pheochromocytoma Cell 3), is a tumor suppressor gene that belongs to an
      antiproliferative gene family. Btg2 is involved in a variety of biological
      processes including cell growth, development, differentiation, senescence, and
      cell death and its expression is strongly regulated by p53. Recently, we have
      reported transient induction of Btg2 expression in response to oxidative damage;
      however, the regulatory mechanism was not explored. In the present study we
      revealed NuFkappaBeta as the upstream mediator involved in Btg2 transcription in
      response to cell stress challenges such as serum deprivation and oxidative stress
      i.e. H2O2, TPA or doxorubicin treatments in several cell lines. We observed close
      interrelation between generation of reactive oxygen species (ROS), enhanced
      IkappaBalpha degradation, nuclear translocation of NuFkappaBeta (p65/RelA) and
      the significant increase of Btg2 expression independent of p53 status. ChIP
      analysis revealed an enrichment of RelA (p65) bound to the kappaB response
      element on Btg2 promoter in response to the cell stress challenges. Employing
      various inhibitors led to cytoplasmic accumulation of IkappaBalpha, decreased p65
      nuclear translocation along with significant reduction of Btg2 expression.
      Generation of ROS was the common event mediating NuFkappaBeta activation and Btg2
      transcription. Furthermore, PKC activation was also found to be a critical factor
      mediating ROS-mediated signals to NFkappaB pathway that culminate on Btg2
      regulation, and specifically PKC-delta was responsible for this regulation under
      oxidative stress. However, serum deprivation-associated ROS generation bypassed
      PKC activation for induction of Btg2 expression via NFkappaB activation. The
      present data imply that oxidative stress upregulates Btg2 expression via ROS-PKC
      NuFkappaBeta cascade, independent of p53 status that in turn could be involved in
      mediating various biological phenotypes depending on the cellular context. 

PMID- 23876795
TI  - Combined CpG and poly I:C stimulation of monocytes results in unique signaling
      activation not observed with the individual ligands.
AB  - Toll-like receptors (TLRs) bind to components of microbes, activate cellular
      signal transduction pathways and stimulate innate immune responses. Previously,
      we have shown in chicken monocytes that the combination of CpG, the ligand for
      TLR21 (the chicken equivalent of TLR9), and poly I:C, the ligand for TLR3,
      results in a synergistic immune response. In order to further characterize this
      synergy, kinome analysis was performed on chicken monocytes stimulated with
      either unmethylated CpG oligodeoxynucleotides (CpG) and polyinosinic
      polycytidylic acid (poly I:C) individually or in combination for either 1h or 4h.
      The analysis was carried out using chicken species-specific peptide arrays to
      study the kinase activity induced by the two ligands. The arrays are comprised of
      kinase target sequences immobilized on an array surface. Active kinases
      phosphorylate their respective target sequences, and these phosphorylated
      peptides are then visualized and quantified. A significant number of peptides
      exhibited altered phosphorylation when CpG and poly I:C were given together, that
      was not observed when either CpG or poly I:C was given separately. The unique,
      synergistic TLR agonist affected peptides represent protein members of signaling
      pathways including calcium signaling pathway, cytokine-cytokine receptor
      interaction and Endocytosis at the 1h time point. At the 4h time point, TLR
      agonist synergy influenced pathways included Adipocytokine signaling pathway,
      cell cycle, calcium signaling pathway, NOD-like receptor signaling pathway and
      RIG-I-like receptor signaling pathway. Using nitric oxide (NO) production as the
      readout, TLR ligand synergy was also investigated using signaling protein
      inhibitors. A number of inhibitors were able to inhibit NO response in cells
      given CpG alone but not in cells given both CpG and poly I:C, as poly I:C alone
      does not elicit a significant NO response. The unique peptide phosphorylation
      induced by the combination of CpG and poly I:C and the unique signaling protein
      requirements for synergy determined by inhibitor assays both show that
      synergistic signaling is not a simple addition of TLR pathways. A set of
      secondary pathways activated by the ligand combination are proposed, leading to
      the activation of cAMP response element-binding protein (CREB), nuclear factor
      kappaB (NFkappaB) and ultimately of inducible nitric oxide synthase (iNOS). Since
      many microbes can stimulate more than one TLR, this synergistic influence on
      cellular signaling may be an important consideration for the study of immune
      response and what we consider to be the canonical TLR signaling pathways. 

PMID- 23876796
TI  - Scalable decision support at the point of care: a substitutable electronic health
      record app for monitoring medication adherence.
AB  - BACKGROUND: Non-adherence to prescribed medications is a serious health problem
      in the United States, costing an estimated $100 billion per year. While poor
      adherence should be addressable with point of care health information technology,
      integrating new solutions with existing electronic health records (EHR) systems
      require customization within each organization, which is difficult because of the
      monolithic software design of most EHR products. OBJECTIVE: The objective of this
      study was to create a published algorithm for predicting medication adherence
      problems easily accessible at the point of care through a Web application that
      runs on the Substitutable Medical Apps, Reusuable Technologies (SMART) platform.
      The SMART platform is an emerging framework that enables EHR systems to behave as
      "iPhone like platforms" by exhibiting an application programming interface for
      easy addition and deletion of third party apps. The app is presented as a point
      of care solution to monitoring medication adherence as well as a sufficiently
      general, modular application that may serve as an example and template for other
      SMART apps. METHODS: The widely used, open source Django framework was used
      together with the SMART platform to create the interoperable components of this
      app. Django uses Python as its core programming language. This allows statistical
      and mathematical modules to be created from a large array of Python numerical
      libraries and assembled together with the core app to create flexible and
      sophisticated EHR functionality. Algorithms that predict individual adherence are
      derived from a retrospective study of dispensed medication claims from a large
      private insurance plan. Patients' prescription fill information is accessed
      through the SMART framework and the embedded algorithms compute adherence
      information, including predicted adherence one year after the first prescription
      fill. Open source graphing software is used to display patient medication
      information and the results of statistical prediction of future adherence on a
      clinician-facing Web interface. RESULTS: The user interface allows the physician
      to quickly review all medications in a patient record for potential non-adherence
      problems. A gap-check and current medication possession ratio (MPR) threshold
      test are applied to all medications in the record to test for current non
      adherence. Predictions of 1-year non-adherence are made for certain drug classes
      for which external data was available. Information is presented graphically to
      indicate present non-adherence, or predicted non-adherence at one year, based on
      early prescription fulfillment patterns. The MPR Monitor app is installed in the
      SMART reference container as the "MPR Monitor", where it is publically available
      for use and testing. MPR is an acronym for Medication Possession Ratio, a
      commonly used measure of adherence to a prescribed medication regime. This app
      may be used as an example for creating additional functionality by replacing
      statistical and display algorithms with new code in a cycle of rapid prototyping
      and implementation or as a framework for a new SMART app. CONCLUSIONS: The MPR
      Monitor app is a useful pilot project for monitoring medication adherence. It
      also provides an example that integrates several open source software components,
      including the Python-based Django Web framework and python-based graphics, to
      build a SMART app that allows complex decision support methods to be encapsulated
      to enhance EHR functionality.

PMID- 23876797
TI  - Transcriptomic and morphological profiling of Aspergillus fumigatus Af293 in
      response to antifungal activity produced by Lactobacillus plantarum 16.
AB  - The morphological effects of an antifungal activity produced by Lactobacillus
      plantarum 16, a malt-production steep water isolate, on two food-associated fungi
      were examined microscopically. Spore germination was completely inhibited in
      Aspergillus fumigatus and Rhizopus stolonifer upon treatment with concentrated
      cell-free supernatant (cCFS) of strain 16. Furthermore, addition of antifungal
      cCFS to germ tubes and hyphae halted further development compared to untreated
      controls. Transcriptome analysis of A. fumigatus Af293 following exposure to
      antifungal cCFS revealed a number of genes with altered transcription involved in
      a variety of cellular functions, most notably cell metabolism, suggesting a
      global metabolic shutdown and subsequent cell death. Increased transcription of
      the global regulator LaeA was also observed indicating that exposure to the
      antifungal activity caused a cellular stress response. 

PMID- 23876798
TI  - Temporal changes of adiponectin plasma levels in patients with acute ischemic
      stroke.
AB  - Adiponectin, an adipocyte-derived hormone, possesses anti-inflammatory
      properties. Its decreased levels were noted in patients with ischemic stroke
      (IS). Animal studies suggest that the decline of adiponectin levels in the acute
      IS phase is a dynamic process. The aim of the present study was to analyze the
      temporal expression of the adiponectin plasma levels in patients with acute IS.
      Thirty-one consecutive patients with first-ever IS (mean age +/- SD: 69.5 +/-
      12.5 years; 12 women) and 26 control subjects (CS; 72.2 +/- 7.6 years; 18 women)
      were included into the study. Plasma adiponectin levels were measured at three
      time points: within first 24 hours, on Days 2-4, and on Days 5-10 days after the
      onset of IS. Adiponectin levels were significantly lower in IS patients on
      admission comparing with CS (medians: 6.0 MUg/ml vs. 11.3 MUg/ml, respectively; P
      < 0.05) and continued to decline at later time points (P < 0.001).

PMID- 23876799
TI  - Surface association of Pht proteins of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae is a major human pathogen responsible for massive global
      morbidity and mortality. The pneumococcus attaches a variety of proteins to its
      cell surface, many of which contribute to virulence; one such family are the
      polyhistidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE. In this study, we
      have examined the mechanism of Pht surface attachment using PhtD as a model.
      Analysis of deletion and point mutants identified a three-amino-acid region of
      PhtD (Q27-H28-R29) that is critical for the process. The analogous region in PhtE
      was also necessary for its attachment to the cell surface. Furthermore, we show
      that a large proportion of the total amount of each Pht protein is released into
      bacterial culture supernatants. Other surface proteins were also released, albeit
      to lesser extents, and this was not due to pneumococcal autolysis. The extent of
      release of surface proteins was strain dependent and was not affected by the
      capsule. Lastly, we compared the fitness of wild-type and DeltaphtABDE
      pneumococci in vivo in a mouse coinfection model. Release of Pht proteins by the
      wild type did not complement the mutant strain, consistent with surface-attached
      rather than soluble forms of the Pht proteins playing the major role in
      virulence. The significant degree of release of Pht proteins from intact bacteria
      may have implications for the use of these proteins in novel vaccines. 

PMID- 23876800
TI  - Virulent Shigella flexneri affects secretion, expression, and glycosylation of
      gel-forming mucins in mucus-producing cells.
AB  - Mucin glycoproteins are secreted in large amounts by the intestinal epithelium
      and constitute an efficient component of innate immune defenses to promote
      homeostasis and protect against enteric pathogens. In this study, our objective
      was to investigate how the bacterial enteropathogen Shigella flexneri, which
      causes bacillary dysentery, copes with the mucin defense barrier. We report that
      upon in vitro infection of mucin-producing polarized human intestinal epithelial
      cells, virulent S. flexneri manipulates the secretion of gel-forming mucins. This
      phenomenon, which is triggered only by virulent strains, results in accumulation
      of mucins at the cell apical surface, leading to the appearance of a gel-like
      structure that favors access of bacteria to the cell surface and the subsequent
      invasion process. We identify MUC5AC, a gel-forming mucin, as a component of this
      structure. Formation of this gel does not depend on modifications of electrolyte
      concentrations, induction of trefoil factor expression, endoplasmic reticulum
      stress, or response to unfolded proteins. In addition, transcriptional and
      biochemical analyses of infected cells reveal modulations of mucin gene
      expression and modifications of mucin glycosylation patterns, both of which are
      induced by virulent bacteria in a type III secretion system-dependent manner.
      Thus, S. flexneri has developed a dedicated strategy to alter the mucus barrier
      by targeting key elements of the gel-forming capacity of mucins: gene
      transcription, protein glycosylation, and secretion. 

PMID- 23876801
TI  - Heme uptake mediated by LHR1 is essential for Leishmania amazonensis virulence.
AB  - The protozoan parasite Leishmania amazonensis is a heme auxotroph and must
      acquire this essential factor from the environment. Previous studies showed that
      L. amazonensis incorporates heme through the transmembrane protein LHR1
      (Leishmania Heme Response 1). LHR1-null promastigotes were not viable, suggesting
      that the transporter is essential for survival. Here, we compared the growth,
      differentiation, and infectivity for macrophages and mice of wild-type, LHR1
      single-knockout (LHR1/Deltalhr1), and LHR1-complemented (LHR1/Deltalhr1 plus
      LHR1) L. amazonensis strains. LHR1/Deltalhr1 promastigotes replicated poorly in
      heme-deficient media and had lower intracellular heme content than wild-type
      parasites. LHR1/Deltalhr1 promastigotes were also less effective in reducing
      ferric iron to ferrous iron, a reaction mediated by the heme-containing parasite
      enzyme LFR1 (Leishmania Ferric Reductase 1). LHR1/Deltalhr1 parasites
      differentiated normally into aflagellated forms expressing amastigote-specific
      markers but were not able to replicate intracellularly after infecting
      macrophages. Importantly, the intracellular growth of LHR1/Deltalhr1 amastigotes
      was fully restored when macrophages were allowed to phagocytose red blood cells
      prior to infection. LHR1/Deltalhr1 parasites were also severely defective in the
      development of cutaneous lesions in mice. All phenotypes observed in
      LHR1/Deltalhr1 L. amazonensis were rescued by expression of episomal LHR1. Our
      results reveal the importance of efficient heme uptake for L. amazonensis
      replication and vertebrate host infectivity, reinforcing the potential usefulness
      of LHR1 as a target for new antileishmanial drugs. 

PMID- 23876802
TI  - DC-LAMP+ dendritic cells are recruited to gastric lymphoid follicles in
      Helicobacter pylori-infected individuals.
AB  - Infection with Helicobacter pylori is associated with development of ulcer
      disease and gastrointestinal adenocarcinoma. The infection leads to a large
      infiltration of immune cells and the formation of organized lymphoid follicles in
      the human gastric mucosa. Still, the immune system fails to eradicate the
      bacteria, and the substantial regulatory T cell (Treg) response elicited is
      probably a major factor permitting bacterial persistence. Dendritic cells (DCs)
      are professional antigen-presenting cells that can activate naive T cells, and
      maturation of DCs is crucial for the initiation of primary immune responses. The
      aim of this study was to investigate the presence and localization of mature
      human DCs in H. pylori-infected gastric mucosa. Gastric antral biopsy specimens
      were collected from patients with H. pylori-associated gastritis and healthy
      volunteers, and antrum tissue was collected from patients undergoing gastric
      resection. Immunohistochemistry and flow cytometry showed that DCs expressing the
      maturation marker dendritic cell lysosome-associated membrane glycoprotein (DC
      LAMP; CD208) are enriched in the H. pylori-infected gastric mucosa and that these
      DCs are specifically localized within or close to lymphoid follicles. Gastric DC
      LAMP-positive (DC-LAMP(+)) DCs express CD11c and high levels of HLA-DR but little
      CD80, CD83, and CD86. Furthermore, immunofluorescence analyses demonstrated that
      DC-LAMP(+) DCs are in the same location as FoxP3-positive putative Tregs in the
      follicles. In conclusion, we show that DC-LAMP(+) DCs with low costimulatory
      capacity accumulate in the lymphoid follicles in human H. pylori-infected gastric
      tissue, and our results suggest that Treg-DC interactions may promote chronic
      infection by rendering gastric DCs tolerogenic. 

PMID- 23876803
TI  - The mucin Muc2 limits pathogen burdens and epithelial barrier dysfunction during
      Salmonella enterica serovar Typhimurium colitis.
AB  - Salmonella enterica serovar Typhimurium is a model organism used to explore the
      virulence strategies underlying Salmonella pathogenesis. Although intestinal
      mucus is the first line of defense in the intestine, its role in protection
      against Salmonella is still unclear. The intestinal mucus layer is composed
      primarily of the Muc2 mucin, a heavily O-glycosylated glycoprotein. The core 3
      derived O-glycans of Muc2 are synthesized by core 3 beta1,3-N
      acetylglucosaminyltransferase (C3GnT). Mice lacking these glycans still produce
      Muc2 but display a thinner intestinal mucus barrier. We began our investigations
      by comparing Salmonella-induced colitis and mucus dynamics in Muc2-deficient
      (Muc2(-/-)) mice, C3GnT(-/-) mice, and wild-type C57BL/6 (WT) mice. Salmonella
      infection led to increases in luminal Muc2 secretion in WT and C3GnT(-/-) mice.
      When Muc2(-/-) mice were infected with Salmonella, they showed dramatic
      susceptibility to infection, carrying significantly higher cecal and liver
      pathogen burdens, and developing significantly higher barrier disruption and
      higher mortality rates, than WT mice. We found that the exaggerated barrier
      disruption in infected Muc2(-/-) mice was invA dependent. We also tested the
      susceptibility of C3GnT(-/-) mice and found that they carried pathogen burdens
      similar to those of WT mice but developed exaggerated barrier disruption.
      Moreover, we found that Muc2(-/-) mice were impaired in intestinal alkaline
      phosphatase (IAP) expression and lipopolysaccharide (LPS) detoxification activity
      in their ceca, potentially explaining their high mortality rates during
      infection. Our data suggest that the intestinal mucus layer (Muc2) and core 3 O
      glycosylation play critical roles in controlling Salmonella intestinal burdens
      and intestinal epithelial barrier function, respectively. 

PMID- 23876804
TI  - Neisseria prophage repressor implicated in gonococcal pathogenesis.
AB  - Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease
      gonorrhea, can infect and colonize multiple mucosal sites in both men and women.
      The ability to cope with different environmental conditions requires tight
      regulation of gene expression. In this study, we identified and characterized a
      gonococcal transcriptional regulatory protein (Neisseria phage repressor [Npr])
      that was previously annotated as a putative gonococcal phage repressor protein.
      Npr was found to repress transcription of NGNG_00460 to NGNG_00463 (NGNG_00460
      00463), an operon present within the phage locus NgoPhi4. Npr binding sites
      within the NGNG_00460-00463 promoter region were found to overlap the -10 and -35
      promoter motifs. A gonococcal npr mutant demonstrated increased adherence to and
      invasion of human endocervical epithelial cells compared to a wild-type
      gonococcal strain. Likewise, the gonococcal npr mutant exhibited enhanced
      colonization in a gonococcal mouse model of mucosal infection. Analysis of the
      gonococcal npr mutant using RNA sequence (RNA-seq) analysis demonstrated that the
      Npr regulon is limited to the operon present within the phage locus.
      Collectively, our studies have defined a new gonococcal phage repressor protein
      that controls the transcription of genes implicated in gonococcal pathogenesis. 

PMID- 23876806
TI  - The p38 MAPK and JNK pathways protect host cells against Clostridium perfringens
      beta-toxin.
AB  - Clostridium perfringens beta-toxin is an important agent of necrotic enteritis
      and enterotoxemia. Beta-toxin is a pore-forming toxin (PFT) that causes
      cytotoxicity. Two mitogen-activated protein kinase (MAPK) pathways (p38 and c-Jun
      N-terminal kinase [JNK]-like) provide cellular defense against various stresses.
      To investigate the role of the MAPK pathways in the toxic effect of beta-toxin,
      we examined cytotoxicity in five cell lines. Beta-toxin induced cytotoxicity in
      cells in the following order: THP-1 = U937 > HL-60 > BALL-1 = MOLT-4. In THP-1
      cells, beta-toxin formed oligomers on lipid rafts in membranes and induced the
      efflux of K(+) from THP-1 cells in a dose- and time-dependent manner. The
      phosphorylation of p38 MAPK and JNK occurred in response to an attack by beta
      toxin. p38 MAPK (SB203580) and JNK (SP600125) inhibitors enhanced toxin-induced
      cell death. Incubation in K(+)-free medium intensified p38 MAPK activation and
      cell death induced by the toxin, while incubation in K(+)-high medium prevented
      those effects. While streptolysin O (SLO) reportedly activates p38 MAPK via
      reactive oxygen species (ROS), we showed that this pathway did not play a major
      role in p38 phosphorylation in beta-toxin-treated cells. Therefore, we propose
      that beta-toxin induces activation of the MAPK pathway to promote host cell
      survival. 

PMID- 23876805
TI  - Inflammation-induced acid tolerance genes gadAB in luminal commensal Escherichia
      coli attenuate experimental colitis.
AB  - Dysregulated immune responses to commensal intestinal bacteria, including
      Escherichia coli, contribute to the development of inflammatory bowel diseases
      (IBDs) and experimental colitis. Reciprocally, E. coli responds to chronic
      intestinal inflammation by upregulating expression of stress response genes,
      including gadA and gadB. GadAB encode glutamate decarboxylase and protect E. coli
      from the toxic effects of low pH and fermentation acids, factors present in the
      intestinal lumen in patients with active IBDs. We hypothesized that E. coli
      upregulates gadAB during inflammation to enhance its survival and virulence.
      Using real-time PCR, we determined gadAB expression in luminal E. coli from ex
      germfree wild-type (WT) and interleukin-10 (IL-10) knockout (KO) (IL-10(-/-))
      mice selectively colonized with a commensal E. coli isolate (NC101) that causes
      colitis in KO mice in isolation or in combination with 7 other commensal
      intestinal bacterial strains. E. coli survival and host inflammatory responses
      were measured in WT and KO mice colonized with NC101 or a mutant lacking the
      gadAB genes (NC101DeltagadAB). The susceptibility of NC101 and NC101DeltagadAB to
      killing by host antimicrobial peptides and their translocation across intestinal
      epithelial cells were evaluated using bacterial killing assays and transwell
      experiments, respectively. We show that expression of gadAB in luminal E. coli
      increases proportionately with intestinal inflammation in KO mice and enhances
      the susceptibility of NC101 to killing by the host antimicrobial peptide cryptdin
      4 but decreases bacterial transmigration across intestinal epithelial cells,
      colonic inflammation, and mucosal immune responses. Chronic intestinal
      inflammation upregulates acid tolerance pathways in commensal E. coli isolates,
      which, contrary to our original hypothesis, limits their survival and colitogenic
      potential. Further investigation of microbial adaptation to immune-mediated
      inflammation may provide novel insights into the pathogenesis and treatment of
      IBDs. 

PMID- 23876807
TI  - Toxin inhibition of antimicrobial factors induced by Bacillus anthracis
      peptidoglycan in human blood.
AB  - Here, we describe the capacity of Bacillus anthracis peptidoglycan (BaPGN) to
      trigger an antimicrobial response in human white blood cells (WBCs). Analysis of
      freshly isolated human blood cells found that monocytes and neutrophils, but not
      B and T cells, were highly responsive to BaPGN and produced a variety of
      cytokines and chemokines. This BaPGN-induced response was suppressed by anthrax
      lethal toxin (LT) and edema toxin (ET), with the most pronounced effect on human
      monocytes, and this corresponded with the higher levels of anthrax toxin receptor
      1 (ANTXR1) in these cells than in neutrophils. The supernatant from BaPGN-treated
      cells altered the growth of B. anthracis Sterne, and this effect was blocked by
      LT, but not by ET. An FtsX mutant of B. anthracis known to be resistant to the
      antimicrobial effects of interferon-inducible Glu-Leu-Arg (ELR)-negative CXC
      chemokines was not affected by the BaPGN-induced antimicrobial effects.
      Collectively, these findings describe a system in which BaPGN triggers expression
      of antimicrobial factors in human WBCs and reveal a distinctive role, not shared
      with ET, in LT's capacity to suppress this response. 

PMID- 23876808
TI  - Emetic potentials of newly identified staphylococcal enterotoxin-like toxins.
AB  - Staphylococcal enterotoxins (SEs) are a common causative agent of food poisoning.
      Recently, many new SE-like (SEl) toxins have been reported, although the role of
      SEls in food poisoning remains unclear. In this study, the emetic potentials of
      SElK, SElL, SElM, SElN, SElO, SElP, and SElQ were assessed using a monkey-feeding
      assay. All the SEls that were tested induced emetic reactions in monkeys at a
      dose of 100 MUg/kg, although the numbers of affected monkeys were significantly
      smaller than the numbers that were affected after consuming SEA or SEB. This
      result suggests that these new SEs may play some role in staphylococcal food
      poisoning. 

PMID- 23876809
TI  - Impact of selective serotonin reuptake inhibitor therapy on heart valves in
      patients exposed to benfluorex: a multicentre study.
AB  - BACKGROUND: Given the association between valvular heart disease and drugs that
      alter serotonin metabolism, concerns have been raised about the possibility of an
      association between selective serotonin reuptake inhibitor (SSRI) use and drug
      induced valvular disease. In France, SSRI use has been suggested to be an
      important confounding factor in the development of heart valve lesions in
      patients exposed to benfluorex in the context of the 'Mediator scandal'. AIMS: To
      address the relationship between SSRI use and valve regurgitation and morphology
      in a large cohort of patients exposed to benfluorex. METHODS: Overall, 832
      consecutive patients exposed to benfluorex prospectively referred to 10 centres
      underwent complete echocardiography examinations according to a standardized
      protocol. Echocardiograms were independently and blindly read off-line by two
      experts. RESULTS: Ninety patients had been exposed to SSRIs for 3 months or more.
      The proportions of patients with no or trivial, mild, moderate or severe mitral
      regurgitation (MR) or aortic regurgitation (AR) were not different between SSRI
      patients and non-SSRI patients (P=0.63 and 0.58, respectively). The frequencies
      of AR >= mild (20 [22.2%] vs 145 [19.5%]; P=0.55) and MR >= mild (14 [15.6%] vs
      118 [15.9%]; P=0.93) were similar in SSRI patients and non-SSRI patients. The
      frequencies of aortic and mitral valve abnormalities suggestive of drug-induced
      toxicity were also similar in the two patient groups. Multivariable logistic
      regression analysis confirmed the absence of any identifiable relationship
      between AR or MR and morphological abnormalities and SSRI use in the present
      cohort. CONCLUSION: Exposure to SSRIs was not associated with an increased risk
      of heart valve regurgitation or morphological abnormalities suggestive of drug
      induced toxicity in this large cohort of patients exposed to benfluorex.

PMID- 23876810
TI  - Cardiac perforation caused by bone cement embolism.

PMID- 23876811
TI  - Natural history of myocardial scarring after radiofrequency ablation of
      ventricular tachycardia: evaluation with comprehensive cardiac magnetic resonance
      imaging.

PMID- 23876812
TI  - TAVI registries: full disclosure?

PMID- 23876813
TI  - Agreement between a partial coherence interferometer and 2 manual keratometers.
AB  - PURPOSE: To establish repeatability and validity of a partial coherence
      interferometry (PCI) device in patients with astigmatism. SETTING: Industry and
      university. DESIGN: Observational studies. METHODS: A prospective study
      determined the agreement between the IOLMaster 500 PCI device and the Marco 1
      position manual keratometer for measurement of mean corneal power, astigmatic
      power, and axis. Interinstrument and interoperator reproducibility was also
      assessed. A retrospective study determined the agreement between the PCI device
      and the Javal 2-position manual keratometer. Repeatability was also assessed. The
      95% limits of agreement (LoA) were determined for all comparisons. RESULTS:
      Comparing the PCI device and the 1-position manual keratometer, the axis was
      within 5 degrees in 72.1% of eyes; the cylinder power differed by 0.18 diopter
      (D) (95% LoA, +/-0.45 D) and the mean power by 0.33 D (95% LoA, +/-0.25 D).
      Comparing the PCI device and the 2-position manual keratometer, the axis was
      within 5 degrees in 77.1% of eyes. The mean difference in cylinder power between
      the 2 instruments was close to zero (95% LoA, +/-0.37 D); however, the mean power
      differed by 0.34 D (95% LoA, +/-0.25 D). The repeatability of the PCI device was
      better than that of both manual keratometers. CONCLUSIONS: Agreement between the
      PCI device and the 2-position manual keratometer for measures of corneal
      astigmatism and axis was excellent. The 1-position manual keratometer gave
      slightly lower estimates of corneal astigmatism, although the agreement for axis
      was excellent. Thus, the PCI device is an appropriate choice for the calculation
      of toric intraocular lenses. FINANCIAL DISCLOSURE: Dr. Bullimore is a consultant
      to Carl Zeiss Meditec AG and Alcon Surgical, Inc. Drs. Buehren and Bissmann are
      employees of Carl Zeiss Meditec AG.

PMID- 23876814
TI  - Effect of arbuscular mycorrhizal fungi on trace metal uptake by sunflower plants
      grown on cadmium contaminated soil.
AB  - Trace metal (TM) pollution of soil is a worldwide problem that threatens the
      quality of human and environmental health. Phytoremediation using plants and
      their associated microbes has been increasingly used as a green technology for
      cleaning up TM-polluted soils. In this study, we investigated the effect of
      inoculating two arbuscular mycorrhizal fungal isolates, Rhizophagus irregularis
      and Funneliformis mosseae, on trace metal uptake by sunflower plants grown in
      soils contaminated with three different Cd concentrations in a greenhouse trial.
      Root colonization, plant dry mass, and plant tissue cadmium (Cd), zinc (Zn), and
      copper (Cu) concentrations in roots and shoots were determined after sunflower
      harvesting. We found that root mycorrhizal colonization rates were not
      significantly affected by Cd treatments. At low soil Cd concentration, R.
      irregularis-inoculated plants had significantly higher shoot Cd and Zn
      concentrations than plants inoculated with F. mosseae and non-inoculated plants.
      However, at high soil Cd concentrations, F. mosseae-inoculated plants had
      significantly lower shoot Cd and Zn concentrations and biological concentration
      factor (BCF) values than plants inoculated with R. irregularis and non-inoculated
      plants. Cadmium was mainly translocated in shoot tissues of R. irregularis
      inoculated plants and sequestered in the rhizosphere of F. mosseae-inoculated
      plants. The results indicate that these AMF strains mediate different tolerance
      strategies to alleviate TM toxicity in their host plants and that inoculation
      with the R. irregularis strain can be used for Cd phytoextraction, whereas this
      F. mosseae strain can be useful for Cd and Zn phytostabilization of contaminated
      soil.

PMID- 23876815
TI  - Testing for turkeys: a novel nurse-led, faith-based community HIV-testing
      initiative.

PMID- 23876816
TI  - Smoking-cessation interventions in people living with HIV infection: a systematic
      review.
AB  - Tobacco smoking remains a prevalent behavior in people living with HIV infection
      (PLWHs) and is associated with impaired immune functioning, increased
      cardiovascular risk, and decreased response to antiretroviral therapy. This
      review presents a critique and synthesis of evidence on effective smoking
      cessation interventions for PLWHs. A comprehensive search identified nine peer
      reviewed intervention studies published between 1989 and 2012. The highest
      likelihood of smoking cessation (range of odds ratios 4.33-5.6) were in two
      randomized controlled trial interventions using cell phone technology. Clinically
      significant reductions in systolic blood pressure, weight gain, and increased
      CD(4+) T-cell count were reported in participants who ceased smoking in three of
      the nine studies. Overall, multistrategy smoking-cessation interventions,
      delivered over multiple sessions, were effective. However, the most effective
      interventions were tailored to the unique individual needs of PLWHs, including
      assessment of and intervention for polysubstance abuse and mental health issues,
      as well as the inclusion of access-promoting elements. 

PMID- 23876817
TI  - Proficiency in condom use among migrant workers.
AB  - Consistent and correct use of condoms is important to prevent the transmission of
      HIV and other sexually transmitted diseases. We evaluated condom use skills on an
      11-point scale in which participants were observed placing a condom on a penile
      model. Participants were 375 sexually active African American and Hispanic
      migrant workers. For analysis, subjects were divided into skilled and unskilled
      groups by a median split of the condom use skills score. Sexual risk behaviors
      were analyzed between condom use skilled and unskilled groups and level of condom
      use skills between African Americans and Hispanics. African Americans showed
      better skills in using condoms, and participants in the condom-use skilled group
      used condoms more frequently. Finally, a logistic regression was conducted to
      find predictors of condom use skills. Significant predictors were ethnicity,
      language, and assistance-related social support (obtaining advice from people who
      could provide tangible assistance).

PMID- 23876818
TI  - Knowledge, attitudes, and practices of OB/GYN nurses and auxiliary staff in the
      care of pregnant women living with HIV.
AB  - The purpose of this study was to explore the knowledge, attitudes, and practices
      (KAP) of health care workers caring for HIV-infected pregnant women. A KAP survey
      was formulated in order to achieve this goal. Obstetric and gynecological
      (OB/GYN) health care workers (n = 121) in both inpatient and outpatient settings
      in an academic and an affiliated community-based hospital in a large urban
      academic medical center in the northeastern United States were surveyed. Findings
      suggest that KAP requires further improvement among OB/GYN staff, particularly in
      the areas of prevention of HIV and psychosocial care of patients with HIV.
      Further research is needed to determine the best strategies to improve clinical
      practice for pregnant women living with HIV. 

PMID- 23876819
TI  - Evaluation of in vitro cytochrome P450 induction and inhibition activity of
      deoxyelephantopin, a sesquiterpene lactone from Elephantopus scaber L.
AB  - Drug metabolism involving cytochrome P450 (CYP) enzymes is a key determinant of
      significant drug interactions. Deoxyelephantopin was evaluated for its effects on
      the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4, and protein
      expression and resultant enzymatic activity. The mRNA and protein expression of
      cytochrome isoforms were carried out using an optimized multiplex qRT-PCR assay
      and Western blot analysis, respectively. Human CYP3A4 protein expression was
      determined using an optimized hCYP3A4-HepG2 cell-based assay and the enzymatic
      activity was evaluated using P450-GloTM CYP3A4 assay. The molecular interaction
      and possible inhibition of deoxyelephantopin of the CYP3A4 enzyme was determined
      in silico and further validated using substrate-specific CYP3A4 inhibition
      assays. Deoxyelephantopin produced no significant effect on the CYP1A2 and CYP2D6
      mRNA and protein expression. However, it has a weak induction effect on CYP3A4 at
      the transcriptional level. In silico docking simulation showed that
      deoxyelephantopin has a weak interaction with CYP3A4 enzyme and it minimally
      affects the metabolism of CYP3A4 substrates. Deoxyelephantopin is not an in vitro
      CYP1A2 and CYP2D6 inducer. It is both a weak in vitro CYP3A4 inducer and
      inhibitor and is unlikely to elicit a clinically significant effect in human. 

PMID- 23876820
TI  - Passiflora manicata (Juss.) aqueous leaf extract protects against reactive oxygen
      species and protein glycation in vitro and ex vivo models.
AB  - The leaf extracts of many species of genus Passiflora have been extensively
      investigated for their biological activities on several rat tissues, but mainly
      in the central nervous system and liver. They posses anxiolytic-like, sedative
      effects and antioxidant properties. Evidences suggest a key role of C
      glycosylflavonoids in the biological activities of Passiflora extracts. Some
      species (such as P. manicata) of the genus are still poorly investigated for
      their chemical and biological activity. In this work, we aim to investigate both
      antioxidant and antiglycation properties of aqueous extract of P. manicata leaves
      (PMLE) in vitro and ex vivo models. Crude extract showed the C-glycosylflavonoid
      isovitexin as the major compound. Isoorientin and vitexin were also identified.
      In TRAP/TAR assay, PMLE showed a significant antioxidant activity. PMLE at
      concentrations of 10 and 100 MUg mL-1 significantly decreasing LDH leakage in rat
      liver slices. Antioxidant effect also was observed by decreased in oxidative
      damage markers in slices hence hydrogen peroxide was added as oxidative stress
      inductor. PMLE inhibited protein glycation at all concentrations tested. In
      summary, P. manicata aqueous leaf extract possess protective properties against
      reactive oxygen species and also protein glycation, and could be considered a new
      source of natural antioxidants.

PMID- 23876821
TI  - Protective effect of cordycepin-enriched Cordyceps militaris on alcoholic
      hepatotoxicity in Sprague-Dawley rats.
AB  - This study was to investigate the protective effect of cordycepin-enriched
      Cordyceps militaris against alcohol-induced hepatotoxicity in Sprague-Dawley
      rats. Alcohol-feeding rats were fed diets with Paecilomyces japonica as CPJ
      group, C. militaris as CCM group, cordycepin-enriched C. militaris as CCMalpha
      group at the 3% (w/w) level and silymarin at the 0.1% (w/w) level for 4 weeks.
      Alcohol administration resulted in a significant increase in the activities of
      aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl
      transpeptidase (gamma-GTP), alkaline phosphatase (ALP), and lactate dehydrogenase
      (LDH) and the levels of blood alcohol and acetaldehyde in serum. However,
      CCMalpha group markedly prevented from alcohol-induced elevation of these
      parameters in serum. CCMalpha group showed the increased both hepatic activities
      of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Unlike the
      action of alcohol treatment on alcoholic fatty liver, CCMalpha group was also
      attenuated lipid droplet accumulation in the hepatocytes. Present study was also
      confirmed the beneficial roles of silymarin (hepatoprotective agent) against
      alcohol-induced liver injury in rats. Therefore, cordycepin-enriched C. militaris
      can be a promising candidate to prevent from alcohol-induced hepatotoxicity.

PMID- 23876822
TI  - Reduced scytonemin isolated from Nostoc commune induces autophagic cell death in
      human T-lymphoid cell line Jurkat cells.
AB  - Nostoc commune is a terrestrial benthic blue-green alga that often forms an
      extended mucilaginous layer on the soil, accumulates on stones and mud in aquatic
      environments. Reduced-scytonemin (R-scy), isolated from N. commune Vaucher, has
      been shown to suppress the human T-lymphoid Jurkat cell growth. To reveal the
      mechanisms underlying the R-scy-mediated inhibition of Jurkat cell growth, we
      examined cell morphology, DNA fragmentation, and microtubule-associated protein
      light chain 3 (LC3) modification in these cells. We observed multiple vacuoles as
      well as the conversion of LC3-I to LC3-II in R-scy-treated cells. These results
      suggest that the R-scy induced Jurkat cell growth inhibition is attributable to
      the induction of type II programmed cell death (PCD II; autophagic cell death or
      autophagy). We further examined the mechanisms underlying R-scy-induced PCDII.
      The cells treated with R-scy produced large amounts of reactive oxygen species
      (ROS), leading to the induction of mitochondrial dysfunction. However, the
      elimination of R-scy-induced ROS by treatment with N-acetyl-L-cysteine (NAC)
      markedly opposed R-scy-induced PCDII. Based on these results, we conclude that
      ROS formation plays a critical role in R-scy-induced PCDII.

PMID- 23876823
TI  - The effect of polymer coatings on physicochemical properties of spray-dried
      liposomes for nasal delivery of BSA.
AB  - This work describes the development of spray dried polymer coated liposomes
      composed of soy phosphatidylcholine (SPC) and phospholipid dimyristoyl
      phosphatidylglycerol (DMPG) coated with alginate, chitosan or trimethyl chitosan
      (TMC), that are able to penetrate through the nasal mucosa and offer enhanced
      penetration over uncoated liposomes when delivered as a dry powder. All the
      liposome formulations, loaded with BSA as model antigen, were spray-dried to
      obtain powder size and liposome size in a suitable range for nasal delivery.
      Although coating resulted in some reduction in encapsulation efficiency, levels
      were still maintained between 60% and 69% and the structural integrity of the
      entrapped protein and its release characteristics were maintained. Coating with
      TMC gave the best product characteristics in terms of entrapment efficiency,
      glass transition (T(g)) and mucoadhesive strength, while penetration of nasal
      mucosal tissue was very encouraging when these liposomes were administered as
      dispersions although improved results were observed for the dry powders.

PMID- 23876824
TI  - Interaction between oxidized polyaniline and oppositely charged amphiphilic
      assemblies in an aqueous/organic biphasic system.
AB  - Amphiphilic assemblies (AAs) are known to interact with polyelectrolytes in such
      a manner that the dynamic AAs retain their structural features, but the
      polyelectrolytes undergo conformational changes. This article reports that a
      charge bearing, rigid, water insoluble and oxidized conjugated polymer,
      polyaniline, can withstand such conformational changes and at the same time force
      the AAs to disassemble. An interfacial setup, comprising of an aqueous/organic
      interface, was utilized to study the disassembly process and the subsequent phase
      transfer phenomenon of the in situ synthesized polymer. It has further been
      demonstrated that the phase transfer occurred only when the concentration of the
      amphiphile was at and above its critical aggregation concentration. Moreover,
      fine dispersions of polyaniline were obtained initially in the aqueous phase and
      later in the organic phase. These fine dispersions suggest possibilities for
      better processing of this otherwise "difficult to process" polymer. The
      disassembly phenomenon was followed by changes in fluorescence emission and UV
      vis absorption spectra of an entrapped probe molecule, recorded before and after
      the interaction. Changes in particle size upon disassembly were studied by
      dynamic light scattering. Dispersions of the polymer in the two phases were
      realized from transmission electron micrographs and UV-vis absorption spectra of
      the dispersed polymer. 

PMID- 23876825
TI  - Investigation of phosphate adsorption onto ferrihydrite by X-ray photoelectron
      spectroscopy.
AB  - The objective of this study was to characterize phosphate adsorption onto
      synthetic 2-lines ferrihydrite using surface analysis by X-ray Photoelectron
      Spectroscopy and batch experiments. Surface analysis of ferrihydrite samples
      before phosphate sorption gives very reproducible Fe:O surface ratios of (1:3+/
      0.1). Phosphate sorption onto ferrihydrite was investigated by means of pH,
      initial phosphate concentration, and ionic strength effects. Additionally,
      potential background electrolyte influence on phosphate adsorption was also
      determined. Phosphate uptake by ferrihydrite significantly increases with
      decreasing pH, with a maximum uptake of 104.8 mg PO4 g(-1) obtained at pH=4.
      Phosphate removal increases with the enhancement of ionic strength in agreement
      with the formation of inner-sphere complexes. The presence of chloride, nitrate,
      and sulfate showed no competing effect on phosphate removal efficiency. Sorption
      kinetics follow a pseudo-second order model (R(2)>0.99) and the Freundlich
      isotherm model adequately describes sorption (R(2)=0.995). The careful
      examination of high resolution Fe 2p, O 1s, and P 2p spectra before and after
      phosphate sorption allows the characterization of the modifications occurring
      onto the ferrihydrite surface. The binding energy of the P 2p peak agrees well
      with that observed in Fe-PO4 compounds. Additionally, binding energy shifts in
      the Fe 2p spectra combined to variations in the relative intensity of the
      components in the high resolution O 1s spectra illustrate well the formation of
      chemical bonding between iron and phosphate anions at the ferrihydrite surface.

PMID- 23876826
TI  - Targeting hyaluronic acid production for the treatment of leukemia: treatment
      with 4-methylumbelliferone leads to induction of MAPK-mediated apoptosis in K562
      leukemia.
AB  - The current study examined the effect of modulation of hyaluronic acid (HA)
      synthesis on leukemia cell survival using the hyaluronic acid synthesis inhibitor
      4-methylumbelliferone (4-MU). Treatment of CML cells with 4-MU led to caspase
      dependent apoptosis characterized by decreased HA production, PARP cleavage, and
      increased phosphorylation of p38. Addition of exogenous HA, the pan caspase
      inhibitor Z-VAD-FMK or the p38 inhibitor SB203580 to 4-MU treated cells was able
      to protect cells from apoptosis. Treatment of tumor-bearing mice with 4-MU led to
      a significant reduction in tumor load which was mediated through the induction of
      apoptosis. 

PMID- 23876827
TI  - Characterization and comparison of pore landscapes in crystalline porous
      materials.
AB  - Crystalline porous materials have many applications, including catalysis and
      separations. Identifying suitable materials for a given application can be
      achieved by screening material databases. Such a screening requires automated
      high-throughput analysis tools that characterize and represent pore landscapes
      with descriptors, which can be compared using similarity measures in order to
      select, group and classify materials. Here, we discuss algorithms for the
      calculation of two types of pore landscape descriptors: pore size distributions
      and stochastic rays. These descriptors provide histogram representations that
      encode the geometrical properties of pore landscapes. Their calculation involves
      the Voronoi decomposition as a technique to map and characterize accessible void
      space inside porous materials. Moreover, we demonstrate pore landscape
      comparisons for materials from the International Zeolite Association (IZA)
      database of zeolite frameworks, and illustrate how the choice of pore descriptor
      and similarity measure affects the perspective of material similarity exhibiting
      a particular emphasis and sensitivity to certain aspects of structures. 

PMID- 23876828
TI  - Can we safely discharge low-risk patients with febrile neutropenia from the
      emergency department?

PMID- 23876830
TI  - Changes in left atrial functional indexes in ischemic stroke patients.
AB  - BACKGROUND: Increased left atrial (LA) size has been proposed as a predictor of
      multiple adverse cardiovascular events including stroke. LA dysfunction can occur
      in the absence of increased LA size. However, the relationship between stroke and
      changes in LA function is not well known. METHODS: Patients with acute ischemic
      stroke and healthy controls were enrolled prospectively. Stroke patients received
      standard work-ups to determine the etiology of their strokes. Those patients with
      significant cardiac arrhythmia and heart failure were excluded. All participants
      received echocardiography examination. Conventional echocardiographic parameters
      were calculated and cardiac contractile characteristics of the left atrium and
      left ventricle were analyzed using vector velocity imaging (VVI) technique.
      RESULTS: In total, 87 patients with acute ischemic stroke and 20 controls were
      recruited. The mitral inflow E-wave velocities were lower and A-wave velocities
      were higher in stroke patients (0.76 +/- 0.19 vs. 0.84 +/- 0.16, p = 0.048; and
      0.97 +/- 0.20 vs. 0.76 +/- 0.11, p < 0.001 respectively). Stroke patients had a
      higher active emptying percent of total LA emptying (60.5 +/- 19.0%) compared
      with that in controls (33.5 +/- 11.7%, p < 0.001). The minimal LA volume was
      larger in stroke patients (15.0 +/- 10.5 mL) than that in controls (9.9 +/- 4.2
      mL, p = 0.021), whereas there was no difference in maximal LA volume between
      stroke patients (37.3 +/- 16.5 mL) and controls (33.3 +/- 9.9 ml, p = 0.366). The
      diastolic emptying index of the LA was significantly lower in stroke patients
      compared with that in controls (61.4 +/- 14.6% vs. 70.2 +/- 11.0%, p = 0.016).
      The mitral A-wave velocity and active emptying percent of total LA emptying were
      significantly higher in all stroke subtypes than those in controls. CONCLUSION:
      Acute ischemic stroke patients had altered mitral inflow velocities and emptying
      function of the left atrium. VVI is convenient for quantitative assessment of
      left atrial volumes and contractile characteristics. Functional changes of LA may
      occur without significant structural changes. Therefore, the clinical
      implications of LA functional indexes require further study.

PMID- 23876831
TI  - Unusual radiological presentation of sirolimus-associated pneumonitis.
AB  - Sirolimus-associated pneumonitis, a rare but serious drug-induced lung injury,
      has become a great concern clinically, because of the increasing use of sirolimus
      (rapamycin) in patients who have been subjected to solid organ transplantation.
      We report sirolimus-associated pneumonitis in two women who underwent renal
      transplantation. At variance with previous reports, the radiological findings
      shown on chest radiographs and computed tomography scans of the chest in these
      two cases were consolidation lesions mainly with minimal interstitial
      abnormalities. Our reported cases highlight that awareness of various
      radiological findings of sirolimus-associated pneumonitis is pivotal for
      physicians to make early diagnosis of the disorder in patients who have undergone
      solid organ transplantation. 

PMID- 23876832
TI  - Efficacy of standard versus enhanced features in a Web-based commercial weight
      loss program for obese adults, part 2: randomized controlled trial.
AB  - BACKGROUND: Commercial Web-based weight-loss programs are becoming more popular
      and increasingly refined through the addition of enhanced features, yet few
      randomized controlled trials (RCTs) have independently and rigorously evaluated
      the efficacy of these commercial programs or additional features. OBJECTIVE: To
      determine whether overweight and obese adults randomized to an online weight-loss
      program with additional support features (enhanced) experienced a greater
      reduction in body mass index (BMI) and increased usage of program features after
      12 and 24 weeks compared to those randomized to a standard online version
      (basic). METHODS: An assessor-blinded RCT comparing 301 adults (male: n=125,
      41.5%; mean age: 41.9 years, SD 10.2; mean BMI: 32.2 kg/m(2), SD 3.9) who were
      recruited and enrolled offline, and randomly allocated to basic or enhanced
      versions of a commercially available Web-based weight-loss program for 24 weeks.
      RESULTS: Retention at 24 weeks was greater in the enhanced group versus the basic
      group (basic 68.5%, enhanced 81.0%; P=.01). In the intention-to-treat analysis of
      covariance with imputation using last observation carried forward, after 24 weeks
      both intervention groups had reductions in key outcomes with no difference
      between groups: BMI (basic mean -1.1 kg/m(2), SD 1.5; enhanced mean -1.3 kg/m(2),
      SD 2.0; P=.29), weight (basic mean -3.3 kg, SD 4.7; enhanced mean -4.0 kg, SD
      6.2; P=.27), waist circumference (basic mean -3.1 cm, SD 4.6; enhanced mean -4.0
      cm, SD 6.2; P=.15), and waist-to-height ratio (basic mean -0.02, SD 0.03;
      enhanced mean -0.02, SD 0.04, P=.21). The enhanced group logged in more often at
      both 12 and 24 weeks, respectively (enhanced 12-week mean 34.1, SD 28.1 and 24
      week mean 43.1, SD 34.0 vs basic 12-week mean 24.6, SD 25.5 and 24-week mean
      31.8, SD 33.9; P=.002). CONCLUSIONS: The addition of personalized e-feedback in
      the enhanced program provided limited additional benefits compared to a standard
      commercial Web-based weight-loss program. However, it does support greater
      retention in the program and greater usage, which was related to weight loss.
      Further research is required to develop and examine Web-based features that may
      enhance engagement and outcomes and identify optimal usage patterns to enhance
      weight loss using Web-based programs. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry (ANZCTR) trial number: ACTRN12610000197033;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=335159 (Archived
      by WebCite at http://www.webcitation.org/6HoOMGb8j).

PMID- 23876833
TI  - Imatinib discontinuation in chronic phase myeloid leukaemia patients in sustained
      complete molecular response: a randomised trial of the Dutch-Belgian Cooperative
      Trial for Haemato-Oncology (HOVON).
AB  - BACKGROUND: Tyrosine kinase inhibitors treatment in responding chronic myeloid
      leukaemia (CML) patients is generally continued indefinitely. In this randomised
      phase II trial, we investigated whether CML patients in molecular response(4.5)
      (MR(4.5), quantitative reverse-transcription polymerase chain reaction (RQ-PCR))
      after previous combination therapy with imatinib and cytarabine may discontinue
      imatinib treatment safely. PATIENTS AND METHODS: Thirty-three patients from the
      HOVON 51 study with an MR(4.5) for at least 2 years who were still on imatinib
      treatment were randomised between continuation of imatinib (arm A, n=18) or
      discontinuation of imatinib (arm B, n=15). RESULTS: After a median follow up of
      36 months since randomisation, 3 patients (17%) in arm A and 10 patients (67%) in
      arm B had a molecular relapse. All 3 relapsing patients in arm A had also stopped
      imatinib after randomisation. All but one relapsing patient relapsed within 7
      months after discontinuation of imatinib. The molecular relapse rate at 12 and 24
      months after randomisation was 0% and 6% (arm A) and 53% and 67% (arm B)
      respectively. As-treated analysis revealed 56% and 61% relapses at 1 and 2 years
      since cessation in patients who discontinued imatinib, in contrast to 0% of
      patients who continued imatinib. All evaluable patients remained sensitive to
      imatinib after reinitiation and regained a molecular response. CONCLUSION: Our
      data suggest that discontinuation of imatinib is safe in patients with durable
      MR(4.5).

PMID- 23876834
TI  - Feasibility of preemptive biomarker profiling for personalised early clinical
      drug development at a Comprehensive Cancer Center.
AB  - PURPOSE: Multiple investigational drugs are currently explored in cancer patient
      populations defined by specific biomarkers. This demands a new process of patient
      selection for clinical trials. PATIENTS AND METHODS: Starting January 1, 2012,
      preemptive biomarker profiling was offered at the West German Cancer Center to
      all patients with advanced non-small-cell lung (NSCLC) or colorectal cancer
      (CRC), who met generic study inclusion criteria. Tumour specimens were subjected
      to prespecified profiling algorithms to detect 'actionable biomarkers' by
      amplicon sequencing, in situ hybridisation and immunohistochemistry. The clinical
      course was closely monitored to offer trial participation whenever applicable.
      RESULTS: Within 12 months, 267 patients (188 NSCLC, 79 CRC) were profiled.
      Estimated additional cost for biomarker profiling was 219615.51 EUR excluding
      histopathology workup and administration. The most prevalent biomarkers in
      pulmonary adenocarcinoma were KRAS mutations (29%), loss of PTEN expression
      (18%), EGFR mutations (9%), HER2 amplification (5%) and BRAF mutations (3%),
      while the prevalence of ALK translocations and PIK3CA mutations was extremely
      low. In pulmonary squamous cell carcinoma FGFR1 amplifications were found in 15%,
      PTEN expression was lost in 20% and DDR2 was mutated in a single case. KRAS
      mutations (41%) predominated in CRC, followed by loss of PTEN expression (16%),
      PIK3CA (5%) and BRAF (5%) mutations. So far 13 patients (5%) have entered
      biomarker-stratified clinical trials. Therapeutic decisions for approved drugs
      were guided in another 45 patients (17%). CONCLUSION: Preemptive biomarker
      profiling can be implemented into the diagnostic algorithm of a large
      Comprehensive Cancer Center. Substantial investments in diagnostics and
      administration are required.

PMID- 23876835
TI  - Epigallocatechin-3-gallate attenuates head and neck cancer stem cell traits
      through suppression of Notch pathway.
AB  - Most solid cancers including head and neck squamous carcinoma (HNSC) are believed
      to be initiated from and maintained by cancer stem cells (CSCs) that are
      responsible for treatment resistance, resulting in tumour relapse.
      Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, can
      potently inhibit cancer growth and induce apoptosis in various cancers, including
      HNSC. However, its effect on HNSC CSCs is not well elucidated. In this study, we
      examined the anti-tumour effect of EGCG on HNSC CSCs. We demonstrated that EGCG
      inhibits the self-renewal capacity of HNSC CSCs by suppressing their sphere
      forming capacity, and attenuates the expression of stem cell markers, such as
      Oct4, Sox2, Nanog and CD44. EGCG treatment augmented cisplatin-mediated
      chemosensitivity by suppressing ABCC2 and ABCG2 transporter genes, which are
      putative molecules of treatment resistance of CSC. In addition, the combination
      treatment of EGCG and cisplatin inhibited tumour formation and induced apoptosis
      in a xenograft model. As one of mechanisms of suppression of HNSC CSC traits,
      EGCG decreased the transcriptional level of Notch, resulting in the inhibition of
      Notch signalling. Collectively, our data suggest that EGCG in combination with
      cisplatin can be used for the management of HNSC CSCs. 

PMID- 23876836
TI  - Assessment of association between neutrophil-to-lymphocyte ratio and coronary
      artery ectasia.

PMID- 23876837
TI  - Platelet distribution width should not be used alone as a direct indicator of
      thromboembolic disorders.

PMID- 23876838
TI  - Gallium-based anti-infectives: targeting microbial iron-uptake mechanisms.
AB  - Microbes have evolved elaborate iron-acquisition systems to sequester iron from
      the host environment using siderophores and heme uptake systems. Gallium(III) is
      structurally similar to iron(III), except that it cannot be reduced under
      physiological conditions, therefore gallium has the potential to serve as an iron
      analog, and thus an anti-microbial. Because Ga(III) can bind to virtually any
      complex that binds Fe(III), simple gallium salts as well as more complex
      siderophores and hemes are potential carriers to deliver Ga(III) to the microbes.
      These gallium complexes represent a new class of anti-infectives that is
      different in mechanism of action from conventional antibiotics. Simple gallium
      salts such as gallium nitrate, maltolate, and simple gallium siderophore
      complexes such as gallium citrate have shown good antibacterial activities. The
      most studied complex has been gallium citrate, which exhibits broad activity
      against many Gram negative bacteria at ~1-5MUg/ml MICs, strong biofilm activity,
      low drug resistance, and efficacy in vivo. Using the structural features of
      specific siderophore and heme made by pathogenic bacteria and fungi, researchers
      have begun to evaluate new gallium complexes to target key pathogens. This review
      will summarize potential iron-acquisition system targets and recent research on
      gallium-based anti-infectives. 

PMID- 23876839
TI  - Quo vadis quorum quenching?
AB  - With the emergence of microbial pathogens increasingly resistant against commonly
      used antibiotics, new treatment strategies are desperately needed. Bacterial
      quorum sensing has attracted a lot of attention over the last decade as a
      potential new target for antimicrobial therapy. Interference with quorum sensing
      signaling, or quorum quenching, might offer new avenues to prevent and/or treat
      bacterial infections via inhibition of virulence factor expression and biofilm
      formation. While many inhibitors of quorum sensing signaling have been described,
      only few have been evaluated in vivo and none has been clinically developed. This
      review will highlight recent findings and discuss interesting future areas where
      quorum quenching might be a promising strategy. 

PMID- 23876840
TI  - Pharmacology on microfluidics: multimodal analysis for studying cell-cell
      interaction.
AB  - Understanding the mechanisms of cell-cell interaction is a key unanswered
      question in modern pharmacology, given crosstalk defects are at the basis of many
      pathologies. Microfluidics represents a valuable tool for analyzing intercellular
      communication mediated by transmission of soluble signals, as occurring for
      example between neurons and glial cells in neuroinflammation, or between tumor
      and surrounding cells in cancer. However, the use of microfluidics for studying
      cell behavior still encompasses many technical and biological challenges. In this
      review, a state of the art of successes, potentials and limitations of
      microfluidics applied to key biological questions in modern pharmacology is
      analyzed and commented. 

PMID- 23876842
TI  - A meta-analysis of randomized trials for repeat revascularization following off
      pump versus on-pump coronary artery bypass grafting.
AB  - To determine whether repeat revascularization rates are increased following off
      pump coronary artery bypass grafting (CABG), we performed a meta-analysis of
      randomized controlled trials of off-pump vs on-pump CABG. Databases including
      MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were
      searched through March 2013 using web-based search engines (PubMed, OVID).
      Studies considered for inclusion met the following criteria: the design was a
      prospective randomized controlled clinical trial; the study population was
      patients undergoing CABG; patients were randomly assigned to off-pump vs on-pump
      CABG and outcomes included repeat revascularization rates at >=1 year. Our
      exhaustive search identified 12 prospective randomized controlled trials of off
      pump vs on-pump CABG. Pooled analysis demonstrated a statistically significant
      38% increase in repeat revascularization rates with off-pump relative to on-pump
      CABG in the fixed-effects model (odds ratio, 1.38; 95% confidence interval, 1.09
      1.76; P = 0.008). In general, exclusion of any single trial from the analysis did
      not substantively alter the overall result of our analysis. There was no evidence
      of significant publication bias. The results of our analysis suggest that off
      pump CABG may increase repeat revascularization rates by 38% over on-pump CABG. 

PMID- 23876841
TI  - Recombinant coxsackievirus A2 and deaths of children, Hong Kong, 2012.
AB  - A natural recombinant of coxsackievirus A2 was found in 4 children with
      respiratory symptoms in Hong Kong, China, during the summer of 2012. Two of these
      children died. Vigilant monitoring of this emerging recombinant enterovirus is
      needed to prevent its transmission to other regions. 

PMID- 23876843
TI  - On the dynamics of SEIRS epidemic model with transport-related infection.
AB  - Transportation amongst cities is found as one of the main factors which affect
      the outbreak of diseases. To understand the effect of transport-related infection
      on disease spread, an SEIRS (Susceptible, Exposed, Infectious, Recovered)
      epidemic model for two cities is formulated and analyzed. The epidemiological
      threshold, known as the basic reproduction number, of the model is derived. If
      the basic reproduction number is below unity, the disease-free equilibrium is
      locally asymptotically stable. Thus, the disease can be eradicated from the
      community. There exists an endemic equilibrium which is locally asymptotically
      stable if the reproduction number is larger than unity. This means that the
      disease will persist within the community. The results show that transportation
      among regions will change the disease dynamics and break infection out even if
      infectious diseases will go to extinction in each isolated region without
      transport-related infection. In addition, the result shows that transport-related
      infection intensifies the disease spread if infectious diseases break out to
      cause an endemic situation in each region, in the sense of that both the absolute
      and relative size of patients increase. Further, the formulated model is applied
      to the real data of SARS outbreak in 2003 to study the transmission of disease
      during the movement between two regions. The results show that the transport
      related infection is effected to the number of infected individuals and the
      duration of outbreak in such the way that the disease becomes more endemic due to
      the movement between two cities. This study can be helpful in providing the
      information to public health authorities and policy maker to reduce spreading
      disease when its occurs. 

PMID- 23876844
TI  - Hepatosplenic gammadelta T-cell lymphoma: an overview.
AB  - Peripheral T-cell lymphomas are a heterogeneous group of lymphoid malignancies.
      Among these, hepatosplenic gammadelta T-cell lymphoma (HTCL) represents an
      aggressive and treatment-resistant subgroup for which new avenues of treatment
      are critically needed. HTCL is characterized by primary extranodal distribution
      of the malignant cells with typical intrasinusoidal infiltration of the liver,
      spleen, and bone marrow, which results in hepatosplenomegaly and peripheral blood
      cytopenias. Another characteristic feature is the expression of gammadelta T-cell
      receptors. HTCL exhibits a rapid progressive course and an extremely poor
      response to currently known therapeutic strategies, with a 5-year overall
      survival rate of only 7%. In this review, we discuss the clinical, pathologic,
      and molecular characteristics of this disease, along with the challenges that are
      associated with its diagnosis and treatment. 

PMID- 23876845
TI  - Recurrent chromosome abnormalities define nonoverlapping unique subgroups of
      tumors in patients with chronic lymphocytic leukemia and known karyotypic
      abnormalities.
AB  - BACKGROUND: A major conclusion drawn from the accumulated cytogenetic data on
      solid tumors and some hematologic malignancies is that tumors progress by the
      acquisition of chromosomal changes, as reflected by more aggressive tumors
      containing a larger number of chromosomal abnormalities. An additional
      observation is that some chromosomal changes appear early in the disease
      progression, and some others appear late. MATERIAL AND METHODS: On the basis of
      this information, a model for karyotypic evolution in chronic lymphocytic
      leukemia (CLL) is presented. The Mitelman Database of Chromosomes in Cancer was
      searched, and 1749 abnormal karyotypes were assessed. The main clones were
      analyzed, and chromosomal gains and losses were used to design a model of genetic
      acquisition based on the calculation of a variable called time to occurrence
      (TO). RESULTS: Our comprehensive study of genetic abnormalities in a large number
      of CLL karyotypes revealed that most CLL has 2 chromosomal aberrations at
      diagnosis. Moreover, the temporal analysis suggests that trisomy 12 is an early
      event in the biological evolution of CLL. CONCLUSION: These results highlight the
      possibility of targeted therapies affecting the genes located on this chromosome
      (cyclin D, cyclin D2, cyclin-dependent kinase 2, and cyclin-dependent kinase 4).

PMID- 23876851
TI  - Obesity, insulin resistance, NASH and hepatocellular carcinoma.
AB  - Epidemiological and clinical data have clearly demonstrated that non-alcoholic
      steatohepatitis (NASH) predisposes risk to the development of hepatocellular
      carcinoma (HCC). NASH is the liver manifestation of metabolic syndrome, which
      constellates obesity, insulin resistance and dyslipidemia. Although the
      percentage of patients diagnosed annually with NASH-associated HCC is still
      relatively low, this number signifies a large population due to the rapidly
      increasing incidence of obesity and diabetes globally. Fundamental studies on
      lipid storage, regulation of adipose factors, inflammatory cytokine recruitments
      and oxidative stress have provided insights into NASH as well as metabolic
      syndrome. Recent evidence also indicates the significant role of genetic factors
      in contributing to the pathogenesis of NASH and induced hepatic malignancy. In
      this review, we attempt to collate current research on NASH biology that lead to
      our understandings on how metabolic disorders may intersect with cancer
      development. We also discuss study models that have supported discoveries of
      molecular and cellular defects, and offered a perspective on therapeutic
      developments. These studies have collectively increased our knowledge on the
      complex signaling pathways involved in NASH and cancer, and provided the
      foundation for improved clinical management of patients with metabolic diseases. 

PMID- 23876852
TI  - Eradication of gastric cancer is now both possible and practical.
AB  - In 1994, Helicobacter pylori was declared a human carcinogen. Evidence has now
      accumulated to show that at least 95% of gastric cancers are etiologically
      related to H. pylori. An extensive literature regarding atrophic gastritis and
      its effects on acid secretion, gastric microflora, and its tight association with
      gastric cancer has been rediscovered, confirmed, and expanded. Methods to
      stratify cancer risk based on endoscopic and histologic findings or serologic
      testing of pepsinogen levels and H. pylori testing have been developed producing
      practical primary and secondary gastric cancer prevention strategies. H. pylori
      eradication halts progressive mucosal damage. Cure of the infection in those with
      non-atrophic gastritis will essentially prevent subsequent development of gastric
      cancer. For all, the age-related progression in cancer risk is halted and likely
      reduced as eradication reduces or eliminates mucosal inflammation and reverses or
      reduces H. pylori-associated molecular events such aberrant activation-induced
      cytidine deaminase expression, double strand DNA breaks, impaired DNA mismatch
      repair and aberrant DNA methylation. Those who have developed atrophic
      gastritis/gastric atrophy however retain some residual risk for gastric cancer
      which is proportional to the extent and severity of atrophic gastritis. Primary
      and secondary cancer prevention starts with H. pylori eradication and cancer risk
      stratification to identify those at higher risk who should also be considered for
      secondary cancer prevention programs. Japan has embarked on population-wide H.
      pylori eradication coupled with surveillance targeted to those with significant
      remaining risk. We anticipate that countries with high gastric cancer burdens
      will follow their lead. We provide specific recommendations on instituting
      practical primary and secondary gastric cancer prevention programs as well
      identifying research needed to make elimination of gastric cancer both efficient
      and cost effective. 

PMID- 23876854
TI  - Towards laparoscopic tissue aspiration.
AB  - The soft tissue aspiration experiment has been further developed for application
      during laparoscopic surgery. The new setup has been tested and validated under
      lab-conditions and came then to in vivo operation. It is to our knowledge the
      first time ever a mechanical experiment has been performed under laparoscopic
      conditions on the human, which enables determining corresponding constitutive
      model equations. As most important results, the feasibility of laparoscopic
      tissue aspiration has been demonstrated and, based on an ad hoc parameter for the
      tissue stiffness, the liver and the stomach gave significantly different
      responses. Furthermore, the determined constitutive behavior for one healthy
      human liver was in line with results obtained from tissue aspiration during open
      surgery. Eventually, laparoscopic tissue aspiration might qualify as minimally
      invasive testing method for tactile feedback systems. The presented results are
      preliminary and more research is required. 

PMID- 23876853
TI  - The effects of birth timing and ambient temperature on the hypothalamic-pituitary
      adrenal axis in 3-4 month old rhesus monkeys.
AB  - Birth timing, a relative measure of the timing of births within a season, has
      been shown to be related to the ways mothers and infant interact as well as to
      infant behavior and physiology. Although effects of birth timing on the
      hypothalamic-pituitary-adrenal (HPA) axis have previously been associated with
      variation in social relationships, these effects could also be related to
      seasonal variation in climate conditions when the birth season is long. The
      current study examines the effects of birth timing and ambient temperature on the
      activity and regulation of the HPA axis in 3-4 month old rhesus monkeys (N=338).
      Subjects were part of a BioBehavioral Assessment in which infants were separated
      from their mothers and relocated to a novel testing environment for a period of
      25h. Four blood samples were collected and assayed for cortisol concentrations
      and reflected HPA response to (1) 2h maternal separation and relocation, (2) 7h
      maternal separation and relocation (sustained challenge), (3) dexamethasone
      suppression, and (4) ACTH challenge. Nonlinear mixed modeling was used to examine
      the independent effects of birth timing and temperature on HPA axis activity and
      regulation over the study period. Results indicated that birth timing and ambient
      temperature both had significant, but opposing effects on the cortisol response
      to sustained challenge. Chronic exposure to low ambient temperatures was
      associated with higher cortisol levels. After controlling for the effect of
      ambient temperature, birth timing was positively associated with cortisol such
      that late-born infants exhibited higher cortisol concentrations than did early
      born infants. These results highlight the fact that climate conditions, even
      mild, subtropical conditions, can have potentially important influences on the
      activity and development of the HPA axis. 

PMID- 23876855
TI  - Cytotoxicity and gene expression changes induced by inorganic and organic
      trivalent arsenicals in human cells.
AB  - Inorganic arsenic (iAs) is a human urinary bladder, skin and lung carcinogen. iAs
      is metabolized to methylated arsenicals, with trivalent arsenicals more cytotoxic
      than pentavalent forms in vitro. In this study, cytotoxicity and gene expression
      changes for arsenite (iAs(III)), monomethylarsonous acid (MMA(III)) and
      dimethylarsinous acid (DMA(III)) were evaluated in three human cell types,
      urothelial (1T1), keratinocyte (HEK001) and bronchial epithelial (HBE) cells,
      corresponding to target organs for iAs-induced cancer. Cells were exposed to
      arsenicals to determine cytotoxicity and to study gene expression changes.
      Affymetrix chips were used to determine differentially expressed genes (DEGs) by
      statistical analysis. Lethal concentrations (LC50) for trivalent arsenicals in
      all cells ranged from 1.6 to 10MUM. MMA(III) and DMA(III) had 4-12-fold greater
      potency compared to iAs. Increasing concentrations of iAs(III) induced more genes
      and additional signaling pathways in HBE cells. At equivalent cytotoxic
      concentrations, greater numbers of DEGs were induced in 1T1 cells compared to the
      other cells. Each arsenical altered slightly different signaling pathways within
      and between cell types, but when altered pathways from all three arsenicals were
      combined, they were similar between cell types. The major signaling pathways
      altered included NRF2-mediated stress response, interferon, p53, cell cycle
      regulation and lipid peroxidation. These results show a similar process
      qualitatively and quantitatively for all three cell types, and support a mode of
      action involving cytotoxicity and regenerative proliferation. 

PMID- 23876856
TI  - Dose-response of diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] in the
      urothelial mucosa of Wistar rats.
AB  - Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a herbicide that induced
      urothelial tumors in the urinary bladder of Wistar rats fed 2500ppm during a long
      term study. The currently suggested non-genotoxic mode of action (MOA) of diuron
      encompasses in succession urothelial necrosis induced by direct cytotoxicity,
      regenerative cell proliferation and sustained urothelial hyperplasia that
      increases the likelihood of neoplasia development. This study evaluated the dose
      response profile of urothelial histological and ultrastructural lesions induced
      by diuron. Sixty male Wistar rats were fed ad libitum diuron mixed in the diet at
      0, 60, 125, 500, 1250, or 2500ppm for 20 weeks. The incidences of urothelial
      simple hyperplasia and the cell proliferation index were significantly increased
      in the diuron-fed 1250 and 2500ppm groups. By scanning electron microscopy, the
      incidences and severity of lesions were significantly increased in the 500 and
      1250ppm groups. The incidences of urothelial hyperplasia in the kidney pelvis
      were significantly increased in the 500, 1250 and 2500ppm groups. The present
      study documents the dose-response influence of diuron on the rat urothelium, with
      a no observed effect level (NOEL) at 125ppm; 1250ppm was as effective as 2500ppm
      at inducing urothelial lesions. 

PMID- 23876857
TI  - PopGen: A virtual human population generator.
AB  - The risk assessment of environmental chemicals and drugs is moving towards a
      paradigm shift in approach which seeks the full replacement animal testing with
      high throughput, mechanistic, in vitro systems. This new vision will be reliant
      on the measurement in vitro, of concentration-dependent responses where prolonged
      excessive perturbations of specific biochemical pathways are likely to lead to
      adverse health effects in an intact organism. Such an approach requires a
      framework, into which disparate data generated using in vitro, in silico and in
      chemico systems, can be integrated and utilised for quantitative in vitro-to-in
      vivo extrapolation (QIVIVE), ultimately to the human population level.
      Physiologically based pharmacokinetic (PBPK) models are ideally suited for this
      and are obligatory in order to translate in vitro concentration-response
      relationships to an exposure or dose, route and duration regime in people. In
      this report we describe PopGen, a virtual human population generator which is a
      user friendly, open access web-based application for the prediction of realistic
      anatomical, physiological and phase 1 metabolic variation in a wide range of
      healthy human populations. We demonstrate how PopGen can be used for QIVIVE by
      providing input to a PBPK model, at an appropriate level of detail, to
      reconstruct exposure from human biomonitoring data. We discuss how the process of
      exposure reconstruction from blood biomarkers, in general, is analogous to
      exposure or dose reconstruction from concentration-response measurements made in
      proposed in vitro cell based systems which are assumed to be surrogates for
      target organs.

PMID- 23876858
TI  - Proteomic profile of keratins in cancer of the gingivo buccal complex:
      consolidating insights for clinical applications.
AB  - Keratins play a major role in several cellular functions. Each tissue type
      expresses a specific set of keratins. The immense potential of keratins as
      diagnostic and prognostic markers for different cancers is emerging. Oral cancer
      is the fifteenth most common cancer worldwide. However, comprehensive information
      on the profile of keratins in the oral cavity is not available. Several
      independent reports have identified keratins using antibody based techniques
      which have pitfalls due to the cross reactivity of the antibodies to this set of
      very homologous proteins. A few recent proteomic studies have reported the
      identification of keratins in head and neck cancer. Majority of the studies have
      used tissues from the head and neck region without specifying subsites. This
      study reports the analysis of enriched preparations of keratins from cancer of
      the gingivo buccal complex (GBC) using MS, 2DE, WB, silver staining of 2DE gels
      and IHC. Our study reveals the absence of K4 and K13 and presence of K14, K16,
      and K17, in cancers of the GBC and combination of these expression patterns in
      the cut margins. This report also shows that K13 is glycosylated. This well
      characterized profile of keratins may have potential to be used in clinics.
      BIOLOGICAL SIGNIFICANCE: In recent years the immense potential of keratins as
      diagnostic and prognostic markers for different cancers is emerging. However,
      comprehensive information on the profile of keratins in the oral cavity is not
      available. Several independent reports have identified keratins using only
      antibody based techniques which have pitfalls due to the cross reactivity of the
      antibodies to this set of very homologous proteins. This study reports the
      analysis of enriched preparations of keratins from a subsite of the oral cavity,
      the gingivo buccal complex (GBC) using mass spectrometry, 2DE, western blotting,
      silver staining of 2DE gels and IHC. The proteomic analysis shows the absence of
      K4 and K13 and presence of K14, K16, and K17 in cancers of the GBC and
      combination of these expression patterns in the cut margins. This well
      characterized profile of keratins from the gingivo buccal complex provides
      defined markers which may have potential to be used in the clinics.

PMID- 23876859
TI  - Alcohol use and HIV risk taking among Chinese MSM in Beijing.
AB  - BACKGROUND: Few studies have used standardized alcohol use measures among men who
      have sex with men in China. METHODS: A cross-sectional study was conducted among
      MSM in Beijing. A computer-assisted self-administered questionnaire was used to
      collect demographics, risk behaviors the Alcohol Use Disorders Identification
      Test (AUDIT). AUDIT uses a cutoff score of >= 8 while AUDIT C uses a score of >=
      4 to classify respondents as problem drinkers. Both include a binge drinking
      measure. RESULTS: A total of 500 participants were recruited using respondent
      driven sampling. HIV and prevalence is estimated to be 6.1% (95% CI 3.7, 9.2).
      Almost half of MSM (42.1%, 95% CI 35.8, 49.0) never had a drink containing
      alcohol in the past year. 5.0% (95% CI 3.1, 7.0) and 8.8% (95% CI 6.1, 11.6) had
      AUDIT score >= 8 and AUDIT-C score >= 4, respectively. Binge drinking was at
      11.8% (95% CI 7.9, 16.0). In multivariate models all measures were associated
      with alcohol during sex, while AUDIT was associated with high level of attitudes
      and perceptions on safe sex (AOR 0.9, 95% CI 0.9,1.0), AUDIT-C with being older
      (AOR 3.5, 95%CI 1.4, 8.8), and HIV status (AOR 2.2, 95% CI 1.4, 10.9), and binge
      drinking with number of male partners (AOR 2.0, 95% CI 1.0, 3.9) and ever having
      had an HIV test (AOR 1.0, 95%CI 0.9, 1.0). Compared to AUDIT >= 8, AUDIT-C >= 4
      and binge drinking were more suitable in identifying HIV risks related to problem
      drinking. CONCLUSIONS: Findings suggest AUDIT is appropriate for use among MSM in
      China and reinforces the need for incorporating problem drinking as part of
      approaches to prevent HIV infection among Chinese MSM.

PMID- 23876861
TI  - Fatal child neglect: characteristics, causation, and strategies for prevention.
AB  - Research in child fatalities because of abuse and neglect has continued to
      increase, yet the mechanisms of the death incident and risk factors for these
      deaths remain unclear. The purpose of this study was to systematically examine
      the types of neglect that resulted in children's deaths as determined by child
      welfare and a child death review board. This case review study reviewed 22 years
      of data (n=372) of child fatalities attributed solely to neglect taken from a
      larger sample (N=754) of abuse and neglect death cases spanning the years 1987
      2008. The file information reviewed was provided by the Oklahoma Child Death
      Review Board (CDRB) and the Oklahoma Department of Human Services (DHS) Division
      of Children and Family Services. Variables of interest were child age, ethnicity,
      and birth order; parental age and ethnicity; cause of death as determined by
      child protective services (CPS); and involvement with DHS at the time of the
      fatal event. Three categories of fatal neglect--supervisory neglect, deprivation
      of needs, and medical neglect--were identified and analyzed. Results found an
      overwhelming presence of supervisory neglect in child neglect fatalities and
      indicated no significant differences between children living in rural and urban
      settings. Young children and male children comprised the majority of fatalities,
      and African American and Native American children were over-represented in the
      sample when compared to the state population. This study underscores the critical
      need for prevention and educational programming related to appropriate adult
      supervision and adequate safety measures to prevent a child's death because of
      neglect.

PMID- 23876860
TI  - Potential role of cardiac calsequestrin in the lethal arrhythmic effects of
      cocaine.
AB  - BACKGROUND: Cocaine-related deaths are continuously rising and its overdose is
      often associated with lethal cardiotoxic effects. METHODS AND RESULTS: Our
      approach, employing isothermal titration calorimetry (ITC) and light scattering
      in parallel, has confirmed the significant affinity of human cardiac
      calsequestrin (CASQ2) for cocaine. Calsequestrin (CASQ) is a major Ca(2+)-storage
      protein within the sarcoplasmic reticulum (SR) of both cardiac and skeletal
      muscles. CASQ acts as a Ca(2+) buffer and Ca(2+)-channel regulator through its
      unique Ca(2+)-dependent oligomerization. Equilibrium dialysis and atomic
      absorption spectroscopy experiments illustrated the perturbational effect of
      cocaine on CASQ2 polymerization, resulting in substantial reduction of its Ca(2+)
      binding capacity. We also confirmed the accumulation of cocaine in rat heart
      tissue and the substantial effects cocaine has on cultured C2C12 cells. The same
      experiments were performed with methamphetamine as a control, which displayed
      neither affinity for CASQ2 nor any significant effects on its function. Since
      cocaine did not have any direct effect on the Ca(2+)-release channel judging from
      our single channel recordings, these studies provide new insights into how
      cocaine may interfere with the normal E-C coupling mechanism with lethal
      arrhythmogenic consequences. CONCLUSION: We propose that cocaine accumulates in
      SR through its affinity for CASQ2 and affects both SR Ca(2+) storage and release
      by altering the normal CASQ2 Ca(2+)-dependent polymerization. By this mechanism,
      cocaine use could produce serious cardiac problems, especially in people who have
      genetically-impaired CASQ2, defects in other E-C coupling components, or
      compromised cocaine metabolism and clearance.

PMID- 23876863
TI  - Surgical results of a muscle transposition procedure for abducens palsy without
      tenotomy and muscle splitting.
AB  - PURPOSE: To report a simple muscle transposition procedure without tenotomy or
      muscle splitting to treat abducens palsy. DESIGN: Retrospective, interventional,
      consecutive case series. METHODS: Nine patients with esotropia resulting from
      abducens palsy whose eyes could not abduct beyond the midline underwent this
      muscle transposition procedure, in which a suture was inserted through the
      temporal margin of each vertical rectus muscle. The same monofilament suture also
      was inserted into each inferotemporal or superotemporal sclera. The lateral
      margin of each vertical rectus muscle was transposed superotemporally or
      inferotemporally and was sutured onto the sclera. All 9 patients underwent
      unilateral muscle transposition, and 6 of the 9 underwent a medial rectus muscle
      recession combined with muscle transposition in the same eye. RESULTS: The
      surgical correction by muscle transposition alone ranged from 24 to 36 prism
      diopters, and that by muscle transposition and recession of the medial rectus
      muscle ranged from 50 to 62 prism diopters. The mean correction was 46.3 +/- 13.1
      prism diopters per eye. All paretic eyes could abduct beyond the midline. No
      major vertical ductional disturbances developed. Anterior segment ischemia did
      not occur in any patients. CONCLUSIONS: This procedure, which achieved the same
      corrective results as other popular procedures, is simple to perform because it
      requires only a suture from the muscle to sclera. Tenotomy or splitting of the
      transposed muscles is unnecessary.

PMID- 23876862
TI  - Adverse childhood experiences, health perception, and the role of shared familial
      factors in adult twins.
AB  - To examine the relationship between adverse childhood experiences (ACE) and
      health perception in adulthood, and to explore the contribution of shared
      familial factors to these associations. Data were collected from 180 female twins
      (90 pairs) from the community-based University of Washington Twin Registry.
      Participants completed questionnaires including the modified ACE Questionnaire,
      Traumatic Life Events Questionnaire, McGill Pain Questionnaire-Short Form, and
      the SF-36. Mixed effects linear regression modeling investigated the effects of
      ACE on indices of health perception controlling for correlated twin data.
      Additional models examined the associations while controlling for the experience
      of physical and/or sexual abuse in childhood; within-twin pair models that
      inherently adjust for familial factors explored shared familial influences. After
      controlling for relevant demographic variables, more ACE was associated with
      worse perceptions of general health (p=.01) and vitality (p=.05) on the SF-36.
      After controlling for childhood physical and/or sexual abuse, the relationship
      between ACE and general health remained significant (p=.01) while vitality was no
      longer significant. None of the associations remained significant after
      accounting for the influence of familial factors. These results support previous
      findings on the negative link between ACE and perceived health in adulthood. The
      detrimental effects of ACE on vitality may be accounted for by the experience of
      childhood physical and/or sexual abuse. Shared familial factors might play a
      partial role in the relationship between ACE and health perception. Future
      research should further investigate the genetic and environmental mechanisms that
      may explain this relationship. 

PMID- 23876864
TI  - Incidence of pineal gland cyst and pineoblastoma in children with retinoblastoma
      during the chemoreduction era.
AB  - PURPOSE: To report on the frequency of cysts and tumors of the pineal gland in
      patients with retinoblastoma. DESIGN: Observational retrospective case control
      study. METHODS:  SETTING: Institutional. study population: Four hundred eight
      patients treated for retinoblastoma from January 2000 to January 2012 at Wills
      Eye Institute, Philadelphia, Pennsylvania, USA. OBSERVATION PROCEDURE: Magnetic
      resonance imaging (MRI) features of the pineal gland were evaluated in all
      patients with retinoblastoma. Characteristics of patients with pineal cysts and
      pineoblastoma were reviewed. MAIN OUTCOME MEASURES: Comparison of frequency of
      pineal gland cyst and pineoblastoma in children managed with systemic
      chemoreduction vs other methods. RESULTS: Of 408 patients, treatment included
      systemic chemoreduction in 252 (62%) and nonchemoreduction methods in 156 (38%).
      Overall, 34 patients (8%) manifested pineal gland cyst and 4 (1%) showed
      pineoblastoma. Of all 408 patients, comparison (chemoreduction vs
      nonchemoreduction) revealed pineal cyst (20/252 vs 14/156, P = .7) and
      pineoblastoma (1/252 vs 3/156, P = .1). The pineal cyst (n = 34) (mean diameter 4
      mm) was asymptomatic (n = 34), followed conservatively (n = 34), and with minimal
      enlargement (n = 2, 9%) but without progression to pineoblastoma. The cyst was
      found in 22 germline and 12 nongermline patients (P = .15). Among the 4 patients
      with pineoblastoma, all had germline mutation and 2 had family history of
      retinoblastoma. Among all patients with family history of retinoblastoma (n =
      45), 2 (4%) developed pineoblastoma. The pineoblastoma was asymptomatic in 2
      patients and symptomatic with vomiting and headache in 2 patients. The mean
      interval from date of retinoblastoma detection to pineal cyst was 2 months
      (median 2, range 0-8 months) and to pineoblastoma was 27 months (median 28, range
      7-46 months). Management included aggressive chemotherapy and radiotherapy, with
      2 survivors. CONCLUSIONS: Pineal gland cyst was incidentally detected in 8% of
      retinoblastoma patients, causing no symptoms, and without progression to
      pineoblastoma. Pineoblastoma was detected in 1% of patients and fewer patients
      who received systemic chemotherapy developed pineoblastoma, possibly indicating a
      systemic protective effect.

PMID- 23876865
TI  - Cost comparison of scleral buckle versus vitrectomy for rhegmatogenous retinal
      detachment repair.
AB  - PURPOSE: To estimate and compare the costs of scleral buckle (SB) and pars plana
      vitrectomy (PPV) for treatment of rhegmatogenous retinal detachment (RRD).
      DESIGN: Cost analysis based on published prospective data comparing SB and PPV
      for RRD repair. METHODS: The costs of initial surgery, postoperative retina
      affecting procedures, and eventual cataract extraction resulting from SB and PPV
      for RRD repair were estimated for both phakic and pseudophakic or aphakic
      patients and then were compared. A univariate sensitivity analysis also was
      performed to examine the sensitivity of our estimations. RESULTS: When
      considering all costs, SB was 10.7% less expensive than PPV for RRD repair in
      phakic patients, whereas PPV was 12% less expensive than SB for RRD repair in
      pseudophakic or aphakic patients. These conclusions were robust in the
      sensitivity analysis. CONCLUSIONS: SB seems to offer a modest cost savings over
      PPV for repair of RRD in phakic patients. However, in pseudophakic and aphakic
      patients, PPV seems to be less expensive than SB.

PMID- 23876866
TI  - Potential causes of incomplete visual rehabilitation at 6 months postoperative
      after descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To determine the various causes of unexpected incomplete visual
      rehabilitation at 6 months postoperative after Descemet membrane endothelial
      keratoplasty (DMEK). DESIGN: Retrospective study of prospectively collected data
      at a tertiary referral center. METHODS: From a larger group of 400 consecutive
      DMEK surgeries, the last 200 consecutive eyes were reviewed for visual discomfort
      despite a best-corrected visual acuity (BCVA) of >=20/25 (>=0.8) or unexpected
      subnormal BCVA (<=20/28; <=0.7) at 6 months after DMEK. Biomicroscopy,
      funduscopy, Pentacam imaging, noncontact specular microscopy, anterior segment
      optical coherence tomography, and surgical videos were used to determine the
      causes of incomplete visual rehabilitation. RESULTS: A total of 69 eyes out of
      178 eyes that were included in the analysis (38.8%) presented with incomplete
      visual rehabilitation after DMEK, further categorized as "primarily patient
      related" in 40 of 178 (22.5%), "primarily graft-related" in 21 of 178 (11.8%),
      and a combination of "patient-/graft-related" in 8 of 178 cases (4.5%).
      Unrecognized pre-existing ocular pathology and/or posterior segment disease in 19
      of 178 eyes (10.7%), clinically significant corneal irregularities and/or central
      corneal scarring often secondary to long-standing preoperative corneal edema in
      14 of 178 eyes (7.9%), or (partial) graft detachment in 20 of 178 eyes (11.2%)
      were the main causes of unexpected incomplete visual rehabilitation. Transient or
      persistent monocular ghost images or diplopia occurred in 10 of 178 eyes (5.6%),
      sometimes requiring contact lens fitting. CONCLUSIONS: In contrast to earlier
      endothelial keratoplasty techniques that may frequently be associated with
      undefined transplant-related subnormal visual outcomes, incomplete visual
      rehabilitation after DMEK may virtually always be explained by concomitant ocular
      pathology or evident graft failure.

PMID- 23876867
TI  - Comparison of the effect of ranibizumab and verteporfin for polypoidal choroidal
      vasculopathy: 12-month LAPTOP study results.
AB  - PURPOSE: To compare the effect of photodynamic therapy (PDT) and intravitreal
      ranibizumab in patients with polypoidal choroidal vasculopathy (PCV). DESIGN:
      Randomized clinical trial. METHODS:  SETTING: Multicenter. STUDY POPULATION:
      Total of 93 patients with treatment-naive PCV. INTERVENTION: Patients were
      randomized to 2 arms. Patients in the PDT arm underwent a single session of PDT
      with verteporfin, and patients in the ranibizumab arm received 3 monthly
      ranibizumab injections at baseline. Additional treatment was performed as needed
      in each arm. MAIN OUTCOME MEASURES: Primary outcome measurement was the
      proportion of patients gaining or losing more than 0.2 logarithm of minimal angle
      of resolution (logMAR) units from baseline. Mean change of logMAR and central
      retinal thickness (CRT) were also evaluated. RESULTS: In the PDT arm (n = 47),
      17.0% achieved visual acuity gain, 55.3% had no change, and 27.7% experienced
      visual acuity loss. The results were 30.4%, 60.9%, and 8.7%, respectively, in the
      ranibizumab arm (n = 46), significantly better than the PDT arm (P = .039). In
      the PDT arm, mean CRT improved (366.8 +/- 113.6 MUm to 289.1 +/- 202.3 MUm, P <
      .001), but logMAR was unchanged (0.57 +/- 0.31 to 0.62 +/- 0.40). The ranibizumab
      arm demonstrated improvement in both CRT (418.9 +/- 168.6 MUm to 311.2 +/- 146.9
      MUm, P < .001) and logMAR (0.48 +/- 0.27 to 0.39 +/- 0.26, P = .003). Mean change
      of logMAR was also greater in the ranibizumab arm (P = .011). CONCLUSION:
      Intravitreal injection of ranibizumab is more effective than PDT for treatment
      naive PCV.

PMID- 23876868
TI  - Age- and hypertension-dependent changes in retinal vessel diameter and wall
      thickness: an optical coherence tomography study.
AB  - PURPOSE: To validate and evaluate the reliability of retinal vessel diameter
      measurements by optical coherence tomography (OCT). The effects of age and
      hypertension on vessel diameter were also examined. DESIGN: Prospective, cross
      sectional study. METHODS: Two hundred thirty-eight eyes (238 subjects) with no
      ocular disease were included. Hypertension was present in 106 subjects and absent
      in 132 subjects. Spectralis HRA+OCT was used to scan a circular region around the
      optic disc. Outer and inner diameters of the 4 largest retinal arteries and veins
      were measured using OCT vascular wall reflections, and vessel wall thickness was
      calculated. RESULTS: Intervisit, interexaminer, and interevaluator intraclass
      correlation coefficients of randomly selected vessel measurements were all
      greater than 0.90. Mean inner arterial and venous diameters were 87.8 +/- 9.4 MUm
      and 113.7 +/- 12.5 MUm, respectively. The OCT-measured mean inner arterial and
      venous diameters were significantly correlated to fundus photography caliber
      measurements (P = .005 and P = .001, respectively). Arterial and venous wall
      thicknesses were 17.4 +/- 2.4 MUm and 13.7 +/- 2.1 MUm, respectively, both of
      which were highly correlated with subject age (arterial: r = 0.612, P < .001,
      venous: r = 0.455, P < .001). Additionally, both mean arterial and venous wall
      thicknesses were significantly greater in subjects with hypertension than in age
      matched subjects without hypertension (P = .020 and P = .015, respectively).
      CONCLUSIONS: Retinal vessel diameter measurements obtained with OCT were highly
      reproducible and vessel wall thicknesses, calculated using outer and inner
      diameter measurements, were significantly thickened by both aging and systemic
      hypertension.

PMID- 23876869
TI  - Spectral-domain optical coherence tomography versus ultrasound biomicroscopy for
      imaging of nonpigmented iris tumors.
AB  - PURPOSE: To evaluate the use of spectral-domain optical coherence tomography
      (SDOCT) for imaging of nonpigmented iris tumors, through its comparison with
      ultrasound biomicroscopy (UBM). DESIGN: Retrospective observational case series.
      METHODS: Consecutive patients with non-pigmented iris tumors, not extending to
      the ciliary body, who were concurrently evaluated with SD-OCT and UBM were
      included. Demographics, anterior segment clinical photographs, images obtained
      with SD-OCT (Cirrus HD-OCT, Zeiss Meditec, Dublin, California, USA) with 5.1.1
      anterior segment software upgrade, and UBM (Humphrey Instruments, San Leandro,
      California, USA) were reviewed. The images produced were compared regarding the
      degree of anterior and posterior tumor surface resolution, internal structures,
      tumor thickness measurement, image artefacts, and overall tumor visualization.
      RESULTS: Thirty-seven patients with nonpigmented iris tumors were included.
      Comparing SDOCT to UBM, the image definitions of anterior tumor surface and
      internal tumor heterogeneity were equivalent. Posterior tumor surface was well
      defined in 54% of SDOCT vs 100% in UBM images. Full tumor thickness measurement
      was possible in 86% of SDOCT vs 100% with UBM. The maximum measurable tumor
      thickness with SDOCT was 1.34 mm. SDOCT images showed optical aberrations such as
      shadowing and ghost images in 22 tumors (59%), which encroached on the tumor
      image in 8 patients (22%). The overall tumor visualization with SDOCT was
      possible in 65% of the iris tumors. CONCLUSIONS: UBM generally provides superior
      imaging quality and reproducible measurements of nonpigmented iris tumors.
      Nevertheless, SDOCT, being a noncontact technique, can be a reliable alternative
      in imaging and following some selected nonpigmented iris tumors.

PMID- 23876870
TI  - Intraocular pressure after implantation of the Visian Implantable Collamer Lens
      With CentraFLOW without iridotomy.
AB  - PURPOSE: To compare the intraocular pressure (IOP) values during a 3-month period
      after implantation of the new Visian Implantable Collamer Lens (ICL; STAAR
      Surgical Company, Nidau, Switzerland) V4c design with CentraFLOW technology
      without iridotomy using a standard procedure followed by implantation of the
      conventional ICL V4b model. DESIGN: Retrospective cohort study. METHODS: This
      study included 17 eyes implanted with the ICL V4b model and 18 eyes implanted
      with the ICL V4c model. The mean preoperative spherical equivalent refractions
      were -7.48 +/- 5.00 diopters and -8.66 +/- 4.2 diopters, respectively. We
      compared the best-corrected distance visual acuity before surgery with the
      uncorrected distance visual acuity after surgery. The intraocular pressure (IOP)
      was measured 1 week, 1 month, and 3 months after surgery. The central vault at 3
      months was measured using optical coherence tomography. RESULTS: Three months
      after surgery, the mean uncorrected distance visual acuities were -0.09 +/- 0.12
      logarithm of the minimal angle of resolution units with the V4b and -0.07 +/-
      0.11 logarithm of the minimal angle of resolution units with the V4c. The mean
      distances between the ICL and the anterior crystalline lens surface were 557 +/-
      224 MUm and 528 +/- 268 MUm for the V4b and V4c, respectively (P = .73). After 1
      week and 1 month, the mean IOPs were 13.7 and 13.3 mm Hg and 14.7 and 15.1 mm Hg,
      respectively. There were no significant differences in IOP within or between
      groups during the follow-up period (P > .05, for all comparisons). CONCLUSIONS:
      The new ICL with the CentraFLOW design seems to provide similar results as its
      predecessors for the correction of moderate to high myopia and maintenance of
      safe IOP levels without iridotomy.

PMID- 23876871
TI  - Iron-sulphur clusters, their biosynthesis, and biological functions in protozoan
      parasites.
AB  - Fe-S clusters are ensembles of sulphide-linked di-, tri-, and tetra-iron centres
      of a variety of metalloproteins that play important roles in reduction and
      oxidation of mitochondrial electron transport, energy metabolism, regulation of
      gene expression, cell survival, nitrogen fixation, and numerous other metabolic
      pathways. The Fe-S clusters are assembled by one of four distinct systems: NIF,
      SUF, ISC, and CIA machineries. The ISC machinery is a house-keeping system
      conserved widely from prokaryotes to higher eukaryotes, while the other systems
      are present in a limited range of organisms and play supplementary roles under
      certain conditions such as stress. Fe-S cluster-containing proteins and the
      components required for Fe-S cluster biosynthesis are modulated under stress
      conditions, drug resistance, and developmental stages. It is also known that a
      defect in Fe-S proteins and Fe-S cluster biogenesis leads to many genetic
      disorders in humans, which indicates the importance of the systems. In this
      review, we describe the biological and physiological significance of Fe-S cluster
      containing proteins and their biosynthesis in parasitic protozoa including
      Plasmodium, Trypanosoma, Leishmania, Giardia, Trichomonas, Entamoeba,
      Cryptosporidium, Blastocystis, and microsporidia. We also discuss the roles of Fe
      S cluster biosynthesis in proliferation, differentiation, and stress response in
      protozoan parasites. The heterogeneity of the systems and the
      compartmentalization of Fe-S cluster biogenesis in the protozoan parasites likely
      reflect divergent evolution under highly diverse environmental niches, and
      influence their parasitic lifestyle and pathogenesis. Finally, both Fe-S cluster
      containing proteins and their biosynthetic machinery in protozoan parasites are
      remarkably different from those in their mammalian hosts. Thus, they represent a
      rational target for the development of novel chemotherapeutic and prophylactic
      agents against protozoan infections. 

PMID- 23876872
TI  - A selective review of advances in coccidiosis research.
AB  - Coccidiosis is a widespread and economically significant disease of livestock
      caused by protozoan parasites of the genus Eimeria. This disease is worldwide in
      occurrence and costs the animal agricultural industry many millions of dollars to
      control. In recent years, the modern tools of molecular biology, biochemistry,
      cell biology and immunology have been used to expand greatly our knowledge of
      these parasites and the disease they cause. Such studies are essential if we are
      to develop new means for the control of coccidiosis. In this chapter, selective
      aspects of the biology of these organisms, with emphasis on recent research in
      poultry, are reviewed. Topics considered include taxonomy, systematics, genetics,
      genomics, transcriptomics, proteomics, transfection, oocyst biogenesis, host cell
      invasion, immunobiology, diagnostics and control. 

PMID- 23876873
TI  - The distribution and bionomics of anopheles malaria vector mosquitoes in
      Indonesia.
AB  - Malaria remains one of the greatest human health burdens in Indonesia. Although
      Indonesia has a long and renowned history in the early research and discoveries
      of malaria and subsequently in the successful use of environmental control
      methods to combat the vector, much remains unknown about many of these mosquito
      species. There are also significant gaps in the existing knowledge on the
      transmission epidemiology of malaria, most notably in the highly malarious
      eastern half of the archipelago. These compound the difficulty of developing
      targeted and effective control measures. The sheer complexity and number of
      malaria vectors in the country are daunting. The difficult task of summarizing
      the available information for each species and/or species complex is compounded
      by the patchiness of the data: while relatively plentiful in one area or region,
      it can also be completely lacking in others. Compared to many other countries in
      the Oriental and Australasian biogeographical regions, only scant information on
      vector bionomics and response to chemical measures is available in Indonesia.
      That information is often either decades old, geographically patchy or completely
      lacking. Additionally, a large number of information sources are published in
      Dutch or Indonesian language and therefore less accessible. This review aims to
      present an updated overview of the known distribution and bionomics of the 20
      confirmed malaria vector species or species complexes regarded as either primary
      or secondary (incidental) malaria vectors within Indonesia. This chapter is not
      an exhaustive review of each of these species. No attempt is made to specifically
      discuss or resolve the taxonomic record of listed species in this document, while
      recognizing the ever evolving revisions in the systematics of species groups and
      complexes. A review of past and current status of insecticide susceptibility of
      eight vector species of malaria is also provided. 

PMID- 23876874
TI  - Next-generation molecular-diagnostic tools for gastrointestinal nematodes of
      livestock, with an emphasis on small ruminants: a turning point?
AB  - Parasitic nematodes of livestock have major economic impact worldwide. Despite
      the diseases caused by these nematodes, some advances towards the development of
      new therapeutic agents and attempts to develop effective vaccines against some of
      them, there has been limited progress in the development of practical diagnostic
      methods. The specific and sensitive diagnosis of parasitic nematode infections of
      livestock underpins effective disease control, which is now particularly
      important given the problems associated with anthelmintic resistance in parasite
      populations. Traditional diagnostic methods have major limitations, in terms of
      sensitivity and specificity. This chapter provides an account of the significance
      of parasitic nematodes (order Strongylida), reviews conventional diagnostic
      techniques that are presently used routinely and describes advances in polymerase
      chain reaction (PCR)-based methods for the specific diagnosis of nematode
      infections. A particular emphasis is placed on the recent development of a
      robotic PCR-based platform for high-throughput diagnosis, and its significance
      and implications for epidemiological investigations and for use in control
      programmes. 

PMID- 23876875
TI  - Fluoxetine and citalopram decrease microglial release of glutamate and D-serine
      to promote cortical neuronal viability following ischemic insult.
AB  - Depression is one of the most common disorders appearing following a stroke, and
      is also a major factor limiting recovery and rehabilitation in stroke patients.
      Antidepressants are the most common prescribed treatment for depression and have
      shown to have anti-inflammatory properties within the central nervous system
      (CNS). The major source of pro-inflammatory factors within the CNS is from
      activated microglia, the innate immune cells of the CNS. Antidepressants have
      been shown to promote midbrain and hippocampal neuronal survival following an
      ischemic insult and this survival is mediated through the anti-inflammatory
      effects on microglia, but the effects on cortical neuronal survival after this
      insult have yet to be investigated. The present study aimed to test and compare
      antidepressants from three distinct classes (tricyclics, monoamine oxidase
      inhibitors, and selective serotonin-reuptake inhibitors [SSRIs]) on the release
      of inflammatory factors and amino acids from activated microglia and whether
      altering this release could affect cortical neuronal viability after an ischemic
      insult. Primary microglia were treated with 1 MUg/ml LPS and/or 10 MUM
      antidepressants, and the various factors released into medium were assayed. Co
      cultures consisting of microglia and primary cortical neurons were used to assess
      the effects of antidepressant-treated activated microglia on the viability of
      ischemic injured neurons. Of the antidepressants tested, most decreased the
      release of the proinflammatory factors nitric oxide, tumor necrosis factor-alpha,
      and interleukin 1-beta from activated microglia. Fluoxetine and citalopram, the
      SSRIs, decreased the release of the amino acids glutamate and d-serine from LPS
      activated microglia. oxygen-glucose deprived (OGD) cortical neurons cocultured
      with LPS-activated microglia pre-treated with fluoxetine and citalopram showed
      greater survival compared to injured neurons co-cultured with untreated activated
      microglia. Microglial release of glutamate and d-serine was shown to be the most
      important factor mediating neuronal survival following antagonism studies. To our
      knowledge, our results demonstrate for the first time that fluoxetine and
      citalopram decrease the release of glutamate and d-serine from LPS-activated
      microglia and this causes an increase in the survival of OGD-injured cortical
      neurons after co-culture.

PMID- 23876876
TI  - Biochemical biomarker responses of green-lipped mussel, Perna canaliculus, to
      acute and subchronic waterborne cadmium toxicity.
AB  - The biochemical responses of the green-lipped mussel, Perna canaliculus, to
      waterborne cadmium (Cd) were investigated in order to delineate toxic mechanisms,
      and the impacts of exposure dose and duration, of this important toxicant in a
      potential sentinel species. Mussels were exposed for either 96 h (acute: 0, 2000,
      4000 MUgL(-1) Cd) or for 28 d (subchronic: 0, 200, 2000 MUgL(-1) Cd), and the
      digestive gland, gill and haemolymph were examined for impacts. Biochemical
      responses measured included those associated with metal detoxification
      (metallothionein-like protein; MTLP), oxidative stress (catalase, lipid
      peroxidation), cellular homeostasis (alkaline phosphatase, Na(+), K(+)-ATPase;
      NKA), and energy utilisation (glycogen, haemolymph protein). Following acute
      exposure, digestive gland glycogen and gill NKA activity were significantly
      altered by Cd exposure relative to levels in mussels exposed to Cd-free seawater.
      Subchronic Cd exposure resulted in a significant increase in MTLP levels in both
      the gill and the digestive gland. This increase was correlated strongly with the
      levels of Cd accumulation measured in these tissues (R=0.957 for gill, 0.964 for
      digestive gland). Catalase activity followed a similar pattern, although the
      correlation with tissue Cd accumulation was not as strong (R=0.907 for gill,
      0.708 for digestive gland) as that for MTLP. Lipid peroxidation increased in the
      digestive gland at Days 7 and 14 at both subchronic Cd levels tested, but this
      effect had largely dissipated by Days 21 and 28 (with the exception of the 2,000
      MUgL(-1) group at Day 28). Alkaline phosphatase activity decreased significantly
      with Cd exposure in both tissues. This effect was observed at both tested
      concentrations in the gill, but only at the highest concentration for digestive
      gland. A decrease in digestive gland glycogen levels was observed in Cd-exposed
      mussels (Days 14 and 21 at 2,000 MUgL(-1)), while haemolymph protein levels
      increased as a result of subchronic Cd exposure. These findings indicated that
      biochemical responses in Cd-exposed mussels were tissue-specific, dose- and time
      dependent, with duration of exposure being the predominant effect. This study
      shows that biochemical changes in Cd-exposed green-lipped mussels can be linked
      to tissue metal accumulation and are consistent with previously reported
      physiological effects. It also suggests that green-lipped mussels are amenable to
      a multiple biomarker approach and may be of use as a bioindicator species for
      monitoring coastal metal pollution.

PMID- 23876877
TI  - Understanding the role of gender in body image research settings: participant
      gender preferences for researchers and co-participants in interviews, focus
      groups and interventions.
AB  - Participant gender preferences for body image researchers, interventionists and
      focus group and intervention co-participants have been largely ignored, despite
      recognition that such characteristics can influence the nature and quality of
      data collected and intervention effects. To address this, Australian women
      (n=505) and men (n=220) completed a questionnaire about their preferences for
      interviewers and focus group facilitators, for teachers delivering school-based
      interventions, and for co-participants in these settings. Women predominantly
      preferred female interviewers and teachers, and mixed-sex co-participants, but
      most had no preference for focus group facilitators. Body dissatisfied women were
      more likely to prefer female researchers and single-sex co-participants. Most men
      did not have specific preferences, however, body dissatisfied men were more
      likely to report a gender preference for interviewers and teachers. Professional
      capabilities, personal qualities and appearance were regarded as important
      researcher characteristics. These findings have important implications for body
      image research, particularly among high-risk groups. 

PMID- 23876878
TI  - Y's Girl: increasing body satisfaction among primary school girls.
AB  - To date, effective body image interventions for preadolescent school girls are
      lacking. The present study sought to evaluate the effectiveness of Y's Girl, a
      published body image curriculum specifically tailored for preadolescent school
      girls. A sample of 60 Grade 6 girls with a mean age of 11.25 (range of 11-12)
      years were allocated either to an intervention or control group and completed
      baseline and posttest measures of body image, thin-ideal internalization, body
      comparison, self-esteem, peer factors, and disordered eating. Findings revealed
      that, compared to the control group, girls receiving the intervention reported
      improved body image, thin-ideal internalization, body comparisons, and self
      esteem at posttest 1 week after the intervention ended. Furthermore, changes in
      body satisfaction were moderated by initial levels of risk-factors. These
      findings provide initial support for Y's Girl as an effective, affordable body
      image intervention for preadolescent girls which can be implemented by teachers. 

PMID- 23876879
TI  - Strategies of catheter ablation of persistent atrial fibrillation.

PMID- 23876880
TI  - Early-phase changes of P-wave characteristics after circumferential pulmonary
      vein isolation.
AB  - BACKGROUND: Circumferential pulmonary vein isolation (CPVI), as the basal
      ablation strategy for treating atrial fibrillation (AF), not only isolates the
      connection between the left atrium (LA) and the pulmonary veins (PVs), but also
      induces extensive atrial endocardia damage. This could have an effect on the
      sinus pulse conduction in the LA and subsequently result in changes of P-wave
      characteristics of surface electrocardiogram (ECG). METHODS: Fifty consecutive
      patients underwent CPVI for symptomatic drug-refractory paroxysmal AF. The 12
      lead ECGs were recorded one day before CPVI and seven days after CPVI at sinus
      rhythm by a standard resting ECG device. Measured characteristics of the P-wave
      consisted of P-wave duration (PWD), P-wave amplitude (PWA), P-wave polarity
      (PWP), P-wave notch, P-wave dispersion and P-wave index. RESULTS: After CPVI, a
      prevalent decrease of PWD, PWA, and P-wave dispersion was observed; a transition
      of P-wave polarity was observed in the leads of III, aVL and aVF. The rate of P
      wave notch decreased significantly in all leads, especially in the leads of II,
      III, aVF and V3. Patients with sinus rhythm had a shorter P-wave dispersion and P
      wave index and had a lower rate of P-wave notch compared with the patients with
      recurrent atrial tachyarrhythmia. CONCLUSION: Observations from using the surface
      ECG showed that CPVI has instant effects on the electrical conduction in the LA,
      and several changes of P-wave characteristics associated with development of AF
      are improved by CPVI.

PMID- 23876881
TI  - Deciding optimal pacing site: utility of cardiac magnetic resonance imaging.

PMID- 23876882
TI  - Pulmonary vein antrum isolation of pre-excited atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein antrum isolation (PVAI) of pre-excited atrial
      fibrillation (AF) is controversial. This study aimed to observe the therapeutic
      effects of PVAI on pre-excited AF. METHODS: Twenty-nine patients with pre-excited
      AF were prospectively divided into a PVAI group (group I, 19 cases) and a control
      group (group II, 10 cases). To each case in group I, PVAI was performed, and then
      electroanatomical mapping of accessory pathways (AP) and ablation were
      constructed on a three-dimensional (3D) map of the valve annulus. Only AP
      ablation was performed in each case of group II. RESULTS: Of the 29 cases, three
      were found to have dual APs, two had intermittent APs, and the remaining 24 had
      single APs. All APs were successfully ablated after the procedure. There were no
      significant statistical differences in the AP procedure duration ((77.4 +/- 21.3)
      minutes vs. (85.3 +/- 13.1) minutes), the AP ablation time ((204 +/- 34) seconds
      vs. (223 +/- 62) seconds) and the AP X-ray exposure time ((18.6 +/- 4.4) minutes
      vs. (19.1 +/- 4.5) minutes) respectively between groups I and II. As compared
      with the control group (5 of 10 cases, 50%), the PVAI group had a significantly
      lower AF recurrence rate (2 of 19 cases, 11%; P < 0.05) during follow-up of (20.5
      +/- 10.0) months. All seven patients who recurred were successfully abolished by
      a second ablation. CONCLUSIONS: In patients with pre-excited AF, PVAI is an
      effective therapeutic approach with a low AF recurrence rate. 3D
      electroanatomical maps of AP contributed to the high success rate of ablation
      without significantly prolonging of operational duration and X-ray exposure time.

PMID- 23876883
TI  - Left ventricular 12 segmental strain imaging predicts response to cardiac
      resynchronization therapy.
AB  - BACKGROUND: The number of non-responders to cardiac resynchronization therapy
      (CRT) exposes the need for better patient selection criteria for CRT. This study
      aimed to identify echocardiographic parameters that would predict the response to
      CRT. METHODS: Forty-five consecutive patients receiving CRT-D implantation for
      heart failure (HF) were included in this prospective study. New York Heart
      Association (NYHA) class, 6-minute walk distance, electrograph character, and
      multi echocardiographic parameters, especially in strain patterns, were measured
      and compared before and six months after CRT in the responder and non-responder
      groups. Response to CRT was defined as a decrease in left ventricular endsystolic
      volume (LVESV) of 15% or more at 6-month follow up. RESULTS: Twenty-two (48.9%)
      patients demonstrated a response to CRT at 6-month follow-up. Significant
      improvement in NYHA class (P < 0.01), left ventricular end-diastolic volume
      (LVEDV) (P < 0.01), and 6-minute walk distance (P < 0.01) was shown in this
      group. Although there was an interventricular mechanical delay determined by the
      difference between left and right ventricular pre-ejection intervals ((42.87 +/-
      19.64) ms vs. (29.43 +/- 18.19) ms, P = 0.02), the standard deviation of time to
      peak myocardial strain among 12 basal, mid and apical segments (Tepsilon-SD)
      ((119.97 +/- 43.32) ms vs. (86.62 +/- 36.86) ms, P = 0.01) and the non-ischemic
      etiology (P = 0.03) were significantly higher in responders than non-responders,
      only the Tepsilon-SD (OR = 1.02, 95% CI = 1.01 - 1.04, P = 0.02) proved to be a
      favorable predictor of CRT response after multivariate Logistic regression
      analysis. CONCLUSION: The left ventricular 12 segmental strain imaging is a
      promising echocardiographic parameter for predicting CRT response.

PMID- 23876885
TI  - Factors influencing outcomes of intra-aortic balloon counterpulsation in elderly
      patients.
AB  - BACKGROUND: Intra-aortic balloon counterpulsation (IABP) is a mechanical cardiac
      assist device that is used for cardiac support. There are no published reports
      about the use of IABP in elderly Chinese patients, especially for those over 80
      years old. The aim of this study was to describe the clinical outcomes,
      influencing factors, and complications in patients >=80 years old and requiring
      IABP. METHODS: We performed a retrospective study of 134 consecutive patients who
      received IABP therapy. Based on age, we defined two groups; those >=80 years old
      and those <80 years old. RESULTS: The overall mortality was 41.8%. Patients >=80
      years old had higher mortality rates than those <80 years old (47.9% vs. 30.2%).
      Patients >=80 years old had fewer successful revascularizations (45.8%) and more
      pulmonary infections (47.9%) than patients <80 years old (60.3% and 30.2%,
      respectively); these differences were statistically significant. The most common
      non-cardiac complication was pulmonary infection. Cardiogenic shock and pulmonary
      infection were risk factors for all-cause, in-hospital mortality, whereas
      revascularization success was a negative risk factor for the >=80 years old
      patients. CONCLUSIONS: IABP may be successfully and safely employed in patients
      >=80 years old, having severe heart disease, with few complications. Patients
      >=80 years old who need IABP therapy are less likely to have a successful
      revascularization and are more likely to develop pulmonary infections than
      patients <80 years old.

PMID- 23876884
TI  - Performance measures for management of chronic heart failure patients with acute
      coronary syndrome in China: results from the Bridging the Gap on Coronary Heart
      Disease Secondary Prevention in China (BRIG) Project.
AB  - BACKGROUND: Chronic heart failure (CHF) is a severe clinical syndrome associated
      with high morbidity and mortality, and with high health care expenditures. No
      nationwide data are currently available regarding the quality of clinical
      management of CHF patients in China. The aim of this study was to assess the
      quality of care of CHF inpatients in China. METHODS: The American College of
      Cardiology/American Heart Association Clinical Performance Measures for Adults
      with Chronic Heart Failure (Inpatient Measurement Set) with slight modifications
      was used to measure the performance status in 612 CHF patients with acute
      coronary syndrome (ACS) from 65 hospitals across all regions of China. RESULTS:
      The implementation rates of guideline recommended strategies for CHF management
      were low. Only 57.5% of the CHF patients received complete discharge
      instructions, 53.6% of the patients received evaluation of left ventricular
      systolic function, 62.8% received an angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker at discharge, and 52.7% received a beta
      blocker at discharge, 56.3% of the smokers received smoking cessation counseling.
      The rate of warfarin utilization was only 9.7% in CHF patients with atrial
      fibrillation. Most patients (81.4%) did not receive all the first four
      treatments. There were marked differences in the quality of CHF management among
      patients with different characteristics. CONCLUSIONS: Performance measures
      provide a standardized method of assessing quality of care, and can thus
      highlight problems in disease management in clinical practice. The quality of
      care for CHF patients with ACS in China needs to be improved.

PMID- 23876886
TI  - Kruppel-like factor 2 might mediate the rapamycin-induced arterial thrombosis in
      vivo: implications for stent thrombosis in patients.
AB  - BACKGROUND: Stent thrombosis is one of severe complications after sirolimus
      eluting stent implantation. Rapamycin (sirolimus) promotes arterial thrombosis in
      in vivo studies. However, the underlying molecular and transcriptional mechanisms
      of this adverse effect have not been thoroughly investigated. This study was
      designed to examine the effects of rapamycin on the expression of the gene,
      Kruppel-like factor 2 (KLF2), and its transcriptional targets in mice. METHODS:
      Mice were randomly divided into four groups: the control group (intraperitoneal
      injection with 2.5% of dimethyl sulfoxide (DMSO) only), rapamycin group
      (intraperitoneal injection with 2 mg/kg of rapamycin only), Ad-LacZ + rapamycin
      group (carotid arterial incubation with Ad-LacZ plus intraperitoneal injection
      with 2 mg/kg of rapamycin 10 days later), and Ad-KLF2 + rapamycin group (carotid
      arterial incubation with Ad-KLF2 plus intraperitoneal injection with 2 mg/kg
      rapamycin 10 days later). The carotid arterial thrombosis formation was induced
      by FeCl3 and the time of arterial thrombosis was determined. Finally, the RNA and
      protein of carotid arteries were extracted for KLF2, tissue factor (TF),
      plasminogen activator inhibitor-1 (PAI-1), endothelial nitric oxide synthase
      (eNOS), thrombomodulin (TM) mRNA and protein analysis. RESULTS: Compared with
      controls, treatment with rapamycin inhibited KLF2, eNOS and TM mRNA and protein
      expression, and enhanced TF and PAI-1 mRNA and protein expression, and shortened
      time to thrombotic occlusion from (1282 +/- 347) seconds to (715 +/- 120) seconds
      (P < 0.01) in vivo. Overexpression of KLF2 strongly reversed rapamycin-induced
      effects on KLF2, eNOS, TM, TF and PAI-1 expression. KLF2 overexpression increased
      the time to thrombotic occlusion to control levels in vivo. CONCLUSIONS:
      Rapamycin induced an inhibition of KLF2 expression and an imbalance of anti- and
      pro-thrombotic gene expression, which promoted arterial thrombosis in vivo.
      Overexpression of KLF2 increased KLF2 expression and reversed time to thrombosis
      in vivo.

PMID- 23876887
TI  - Clinical and pathological features and imaging manifestations of bronchial
      anthracofibrosis: the findings in 15 patients.
AB  - BACKGROUND: Bronchial anthracofibrosis (BAF) has been defined as a luminal
      narrowing associated with anthracotic pigmentation on bronchoscopy without a
      relevant history of pneumoconiosis or smoking. The aim of the study is to study
      the clinical features and imaging manifestations of BAF, and to promote the
      awareness of this disease. METHOD: Between October 2006 and January 2012, 15
      patients were diagnosed at our department as BAF that showed a narrowing or
      obliteration of lobar or segmental bronchi with anthracotic pigmentation in the
      overlying mucosa on bronchoscopy. The medical records including clinical
      features, imaging manifestations, electronic bronchoscopic findings, and
      pathological features were analysed, and the literature was reviewed. RESULTS: A
      total of 15 patients were analyzed; 13 were female (86.7%) and two were male
      (13.3%) and the age range was from 62 to 86 years with a mean age of 74.5 years.
      Three cases (20.0%) had a history of tuberculosis. The most common clinical
      symptoms of BAF were cough (100%), expectoration (73.3%), dyspnea (60.0%), and
      fever (46.7%). Twelve cases displayed mild to moderate obstructive ventilatory
      dysfunction. In the electronic bronchoscopic evaluation, the most common findings
      were black bronchial mucosal pigmentation, bronchial stenosis, bronchial
      occlusion, and bronchial mucosal folds. Pathological evaluation revealed chronic
      inflammation of the bronchial mucosa, submucosal carbon particle deposition, and
      mucosal or submucosal fibrosis. Chest CT scans showed that 15 patients had
      bronchial stenosis or obstruction (direct signs) with the right middle lobe being
      the most common site (11 cases, 73.3%). The indirect sign was mainly the presence
      of bronchial obstructive diseases (including secondary infection), represented by
      11 cases of pulmonary consolidation (73.3%), seven cases of atelectasis (46.7%),
      and five cases of nodules (33.3%). The CT mediastinal window showed bronchial
      lymph node lesions, mediastinal lymph node calcification (12 cases, 80.0%), and
      enlargement of multiple mediastinal lymph nodes. CONCLUSIONS: The diagnosis of
      BAF was mainly based on bronchoscopic evaluation. Its pathogenesis is currently
      unclear, although it may be related to tuberculosis or bio-fuel inhalation. The
      diagnosis of BAF has important clinical significance, and improved awareness of
      this disease will contribute to prevention of unnecessary thoracotomies.

PMID- 23876888
TI  - Huge clear cell squamous cell carcinoma of the head.

PMID- 23876889
TI  - Penetration of erythromycin through Staphylococcus epidermidis biofilm.
AB  - BACKGROUND: The catheter related infection caused by Staphylococcus epidermidis
      biofilm is increasing and difficult to treat by antimicrobial chemotherapy. The
      properties of biofilms that give rise to antibiotic resistance are only partially
      understood. This study aimed to elucidate the penetration of erythromycin through
      Staphylococcus epidermidis biofilm. METHODS: The penetration ratio of
      erythromycin through Staphylococcus epidermidis biofilms of 1457, 1457-msrA, and
      wild isolate S68 was detected by biofilm penetration model at different time
      points according to the standard regression curve. The RNA/DNA ratio and the cell
      density within the biofilms were observed by confocal laser microscope and
      transmission electromicroscope, respectively. RESULTS: The penetration ratios of
      erythromycin through the biofilms of 1457, 1457-msrA, and S68 after cultivation
      for 36 hours were 0.93, 0.55 and 0.4, respectively. The erythromycin penetration
      ratio through 1457 biofilm (0.58 after 8 hours) was higher than that through the
      other two (0.499 and 0.31 after 24 hours). Lower growth rate of the cells in
      biofilm was shown, with reduction of RNA/DNA proportion observed by confocal
      laser microscope through acridine orange stain. Compared with the control group
      observed by transmission electrmicroscope, the cell density of biofilm air face
      was lower than that of agar face, with more cell debris. CONCLUSIONS:
      Erythromycin could penetrate to the Staphylococcus epidermidis biofilm, but could
      not kill the cells thoroughly. The lower growth rate of the cells within biofilm
      could help decreasing the erythromycin susceptibility.

PMID- 23876890
TI  - HLA-G expression in the peripheral blood of live kidney transplant recipients.
AB  - BACKGROUND: The human leukocyte antigen-G (HLA-G) has been considered to be an
      important tolerogeneic molecule playing an essential role in maternal-fetal
      tolerance, upregulated in the context of transplantation, malignancy, and
      inflammation, and has been correlated with various clinical outcomes. The aim of
      this study was to investigate the clinical relevance of the expression of
      membrane HLA-G (mHLA-G), intracellular HLA-G (iHLA-G), and soluble HLA-G (sHLA-G)
      in the peripheral blood of live kidney transplant recipients. METHODS: We
      compared the expression of the three HLA-G isoforms in three groups, healthy
      donors (n=20), recipients with acute rejection (n=19), and functioning
      transplants (n=30). Flow cytometry was used to detect the expression of mHLA-G
      and iHLA-G in the T lymphocytes of peripheral blood from subjects in the three
      groups. Enzyme-linked immunosorbent assays were used to detect sHLA-G in the
      plasma from the three groups. RESULTS: There were no significant differences in
      mHLA-G and intracellular HLA-G among the three groups, but the sHLA-G plasma
      level was higher in the functioning group than in the acute rejection or healthy
      group. We found a subset of CD4(+)HLA-G(+) and CD8(+)HLA-G(+) T lymphocytes with
      low rates of mHLA-G expression in the peripheral blood of kidney transplantation
      recipients. Intracellular expression of HLA-G was detected in T lymphocytes.
      However, there was no correlation between acute rejection and the mHLA-G or
      intracellular HLA-G expression. CONCLUSION: sHLA-G was the major isoform in the
      peripheral blood of live kidney transplant recipients and high sHLA-G levels were
      associated with allograft acceptance.

PMID- 23876891
TI  - Schwannomatosis: a new member of neurofibromatosis family.
AB  - BACKGROUND: Schwannomatosis is a recently recognized peripheral nerve
      polyneoplasm with clinical characteristics and a genetic background that differ
      from those of neurofibromatosis 2 (NF2). The diagnostic and treatment criteria of
      this rare disorder are herein discussed. METHODS: The data of 180 patients who
      underwent operations for benign schwannomas from 2003 to 2012 in our center were
      reviewed. Eight of them were classified as schwannomatosis according to the
      diagnostic criteria suggested by MacCollin. The demographic characteristics were
      documented and compared between the two groups of patients. The patients'
      clinical presentations, imaging characteristics, histological features, and
      treatment results were retrospectively investigated and summarized. RESULTS: Of
      the 180 cases of benign schwannomas we reviewed this time, eight patients
      presented with schwannomatosis (4.44%). The mean age of the two groups was not
      significantly different (40.0 vs. 44.7 years, t = 0.88, P = 0.378). However,
      schwannnomatosis seems to more generally occur in females (75% vs. 48% were
      females, P = 0.162), although the difference was not statistically significant.
      The initial main symptom was pain. The neurological examination was otherwise
      normal. Magnetic resonance imaging (MRI) revealed multiple discrete, well-defined
      round, or oval lesions distributed along the course of the peripheral nerves in
      the extremities with low-to-intermediate signal intensity on T1-weighted images
      and high-signal intensity on T2-weighted images. Vestibular schwannomas were
      excluded in four patients by cranial MRI. The lesions in all patients were
      resected and were pathologically proven to be schwannomas. The average follow-up
      period was 26 months. Six individuals obtained a good result without symptoms or
      function loss. CONCLUSIONS: Schwannomatosis is characterized by the development
      of multiple schwannomas without evidence of the vestibular tumors that are
      diagnostic for NF2. It commonly occurs in middle-aged females. It has similar
      demographic features to solitary benign schwannoma. Surgical resection always
      results in a good outcome.

PMID- 23876892
TI  - Effect of angiotensin II type I receptor blocker losartan on bone deterioration
      in orchiectomized male hypertensive and normotensive rats.
AB  - BACKGROUND: Epidemiological study showed that the use of angiotensin-converting
      enzyme inhibitors was associated with higher bone mineral density (BMD) in older
      people, especially male subjects, which suggested that angiotensin II may have a
      detrimental effect on bone. Therefore, blocking its effect may have a beneficial
      effect on bone health. METHODS: Six-month-old male spontaneously hypertensive
      rats (SHR) and normotensive Wistar Kyoto rats (WKY) were used. Animals of each
      model were randomly assigned to the following four groups: Group 1, SHAM
      operated+vehicle; Group 2, orchidectomy (ORX)+vehicle; Group 3, ORX+low-dose
      losartan (10 mg*kg(-1)*d(-1)); and Group 4, ORX+high-dose losartan (25 mg*kg(
      1)*d(-1)). Blood pressure was recorded weekly. SHAM and ORX operations were
      performed, followed by daily losartan and vehicle treatment from day 4 after
      operation for 16 weeks. Serum and 24-hour urine samples were collected for
      measurement of bone turnover markers before euthanasia and then the left femur
      was collected for measurements of BMD and microarchitecture before mechanical
      test. RESULTS: Urine deoxypyridinoline/urine creatinine (DPD/Cr) ratio was
      significantly higher in SHR than in WKY. BMD and microarchitecture parameters
      also showed bone deterioration in SHR. After ORX, serum osteocalcin concentration
      decreased and urine DPD/Cr ratio increased significantly accompanied by a
      significant decrease in cortical and trabecular BMD and cortical bone thickness
      in both WKY and SHR. High-dose losartan significantly increased DPD in urine in
      both SHR and WKY. Apart from marginal favorable changes in bone architecture in
      WKY treated with high-dose losartan, losartan did not show significant effect on
      BMD, bone area, bone microarchitecture, and mechanical properties in both SHR and
      WKY. CONCLUSION: Angiotensin II type I receptor blocker losartan was not able to
      demonstrate significant effect on ORX-induced bone deterioration in both
      hypertensive and normotensive rats.

PMID- 23876893
TI  - Efficacy of mouth opening exercises in treating trismus after maxillectomy.
AB  - BACKGROUND: Patients with maxillary tumor often suffer from trismus after
      maxillectomy, which could turn out to be a permanent sequela without proper
      intervention. In this study, the efficacy of mouth opening exercises in
      preventing and treating trismus was observed in patients with maxillary tumor
      early after their operations. At the same time, radiotherapy as an influencing
      factor for the mouth opening exercises was evaluated. METHODS: In this study, 22
      patients with maxillary oncology began their mouth opening exercises at an early
      stage (1-2 weeks) after maxillectomy. They were divided into two groups based on
      the principle of voluntariness: 11 patients in group 1 chose TheraBites as their
      instruments of mouth opening exercises, and the other 11 in group 2 chose stacked
      tongue depressors to help their exercises. All participants were trained to
      exercise 3-5 times a day, 30-40 oscillations at one time, with a 2-second pause
      at their maximum possible mouth open position. The maximal interincisor distances
      (MID) of patients were measured and recorded by a single investigator every week
      after the beginning of the mouth opening exercises. Medical information and the
      responses of patients were also recorded. Initial and final MIDs were calculated
      by SPSS 13.0. RESULTS: The changes of the mouth aperture every week during
      exercises in both groups were described in figures, and there were statistical
      increases in the final MIDs compared with the initial ones. However, no
      significant differences were achieved between groups 1 and 2 (P > 0.05).
      Radiotherapy seemed to have no negative impact on the mouth opening results
      during the exercises. CONCLUSION: Physical mouth opening exercises should be
      executed early after maxillectomy for the prevention and treatment of trismus,
      especially for those who had radiotherapy as part of antitumor treatments.

PMID- 23876894
TI  - Antimicrobial activity of linezolid combined with minocycline against vancomycin
      resistant Enterococci.
AB  - BACKGROUND: Vancomycin-resistant Enterococci (VRE) cause serious infections that
      are difficult to treat. We carried out this study to determine the mutant
      prevention concentration (MPC) of linezolid when combined with minocycline
      against VRE strains, to determine the mechanism of drug resistance in vitro, and
      to provide a theoretical basis for the rational use of drugs against VRE.
      METHODS: The minimum inhibitory concentrations (MICs) of linezolid and
      minocycline against 30 Enterococci (E.) isolates (including 20 VRE strains) were
      determined by the broth microdilution method. Drug interactions were assessed by
      the checkerboard microdilution tests and confirmed by time-kill studies. Two
      vancomycin-susceptible strains N27 and N40 (linezolid MIC, 2 g/ml; minocycline
      MIC, 4 ug/ml) and control strains E. faecalis ATCC 29212 and ATCC 51299 were also
      tested. The MPCs of linezolid and minocycline (alone and combined) were
      determined using the agar dilution method. Strains showing stable resistance were
      analyzed by polymerase chain reaction (PCR) amplification of domain V of the 23S
      rRNA gene. RESULTS: Checkerboard titration studies revealed synergistic effects
      of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed.
      The G2576U mutation was detected in stable linezolid-resistant strains of ATCC
      29212, N40, and N27 before and after resistance screening, and MIC values
      increased with the number of G2576U mutations. The MPC of linezolid against E.
      decreased dramatically when combined with minocycline, and vice versa.
      CONCLUSION: Linezolid or minocycline alone produce resistant strains; however,
      their joint use may reduce the MPC of each agent against VRE, thereby decreasing
      resistant mutants and bacterial infections.

PMID- 23876895
TI  - MiRNA-365 and miRNA-520c-3p respond to risperidone treatment in first-episode
      schizophrenia after a 1 year remission.
AB  - BACKGROUND: MicroRNAs (miRNAs) control gene expression by destabilizing target
      transcripts and inhibiting their translation. Aberrant expression of miRNAs has
      been described in many human diseases, including schizophrenia. However, the
      effects on miRNA expression in response to antipsychotic treatment in peripheral
      circulation have not been thoroughly examined. METHODS: Using quantitative real
      time PCR (qRT-PCR), We quantified the expression of seven candidate miRNAs in
      plasma samples of 40 first-episode schizophrenics before and after antipsychotic
      treatment. The patients were all treated with risperidone and achieved remission
      in 1 year. RESULTS: Compared with the baseline, the expression levels of miR-365
      and miR-520c-3p were significantly down-regulated after 1 year of risperidone
      treatment (P < 0.001). There were no significant correlations between the
      clinical symptoms and the expression levels of these two miRNAs (P > 0.05).
      CONCLUSIONS: This study analyzed possible circulating miRNAs in response to
      antipsychotic monotherapy for schizophrenia, the further mechanism need to be
      confirmed.

PMID- 23876896
TI  - Clinicopathological significance of altered metallothionein 2A expression in
      gastric cancer according to Lauren's classification.
AB  - BACKGROUND: Dysregulated metallothionein 2A (MT2A) has been implicated in
      carcinogenesis. The purpose of this study was to investigate the expression of
      MT2A in gastric cancer (GC) and its correlation with prognosis. METHODS: Reverse
      transcription-polymerase chain reaction and real-time polymerase chain reaction
      were used to detect the mRNA expression of MT2A in 12 GC cell lines, normal
      gastric epithelial GES-1 cells, and 36 GC and adjacent normal tissues. MT2A
      protein expression was determined in 258 GC tissues and 171 adjacent normal
      tissues by immunohistochemistry. RESULTS: MT2A mRNA expression was lower in GC
      cells and primary tumors than in GES-1 cells and adjacent normal tissues,
      respectively. High protein expression of MT2A was present in 130 of 171 normal
      tissues (76.0%) and in 56 of 258 GC tissues (21.7%; P < 0.001). MT2A protein
      expression was higher in well/moderately differentiated GC (22/54; 40.7%) than in
      poorly differentiated GC (34/204; 16.7%; P < 0.001). Moreover, the protein
      expression of MT2A was lower in diffuse-type GC (6/82; 7.3%) than in intestinal
      type GC (50/176; 28.4%; P = 0.0001). Importantly, MT2A expression was an
      independent prognostic factor for GC, and decreased MT2A expression was
      associated with poor clinical outcome (P < 0.001). The expression status of MT2A
      could predict prognosis in intestinal and diffuse-type GCs. CONCLUSION:
      Expression status of MT2A might be a useful prognostic biomarker for GC,
      especially when used in combination with Lauren's classification.

PMID- 23876897
TI  - Experience of segmentectomy from 36 Chinese patients with non-small cell lung
      cancer at stage I.
AB  - BACKGROUND: Although video-assisted radical operation for lung cancer has been
      widely accepted for treatment of nonsmall cell lung cancer (NSCLC), the debate
      over video-assisted thoracic surgery (VATS) segmentectomy still remains. This
      study analyzed the clinical outcomes using VATS segmentectomy for stage I NSCLC
      patients to explore the safety and efficacy of VATS segmentectomy for Ia NSCLC.
      METHODS: Retrospective review was conducted of patients who underwent VATS
      segmentectomy for clinical stage I NSCLC at Shanghai Chest Hospital between
      November 2009 and May 2012. VATS segmentectomy was performed on 36 patients.
      Analyses of the patient group were performed on patient demographics and clinical
      characteristics, intraoperative parameters, complications, and postoperative
      survival. RESULTS: Thirty-five of thirty-six patients underwent VATS
      segmentectomy with only one conversion to open thoracic surgery. There was one
      peri-operative mortality from the segmentectomy group and all other patients are
      alive with a median follow up of 327 days. The mean volume of chest tube drainage
      after operation for segmentectomy was 1021.4 ml. Among other parameters, the mean
      blood loss was 162.5 ml (50.0 - 1600.0 ml), the mean operation time 124.8 minutes
      (75.0 - 271.0 minutes), chest tube duration 4.1 days (2 - 8 days), and the mean
      length of hospital stay 6.2 days (4 - 11 days). There was one (2.8%) locoregional
      recurrence after segmentectomy. Two patients successfully underwent bilateral
      segmentectomies and are still disease free. CONCLUSION: For patients with stage I
      NSCLC, VATS segmentectomy offers a safe and equally effective option and can be
      applied to complicated operations such as bilateral segmentectomy.

PMID- 23876898
TI  - Effect of cAMP on short-circuit current in isolated human ciliary body.
AB  - BACKGROUND: Cyclic adenosine monophosphate (cAMP) could activate chloride
      channels in bovine ciliary body and trigger an increase in the ionic current
      (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of
      this study was to investigate how cAMP modulates Isc in isolated human ciliary
      processes and the possible involvement of chloride transport across the tissue in
      cAMP-induced Isc change. METHODS: In an Ussing-type chamber system, the Isc
      changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase
      activator forskolin in isolated human ciliary processes were assessed. The
      involvement of Cl(-) component in the bath solution was investigated. The effect
      of Cl(-) channel (10 umol/L niflumic acid and 1 mmol/L 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L
      tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L
      amiloride) on 8-bromo-cAMP-induced Isc change was also studied. RESULTS: Dose
      dependently, 8-bromo-cAMP (10 nmol/L-30 umol/L) or forskolin (10 nmol/L-3 umol/L)
      increased Isc across the ciliary processes with an increase in negative potential
      difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase
      induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE
      side than on the pigmented epithelium side. When the tissue was bathed in low Cl(
      ) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid
      and DIDS, but not TEA or amiloride, significantly prevented the Isc increase
      induced by 8-bromo-cAMP. CONCLUSIONS: cAMP stimulates stroma-to-aqueous anionic
      transport in isolated human ciliary processes. Chloride is likely to be among the
      ions, the transportation of which across the tissue is triggered by cAMP,
      suggesting the potential role of cAMP in the process of aqueous humor formation
      in human eyes.

PMID- 23876899
TI  - Long-term outcome of operative management of delayed acetabular fractures.
AB  - BACKGROUND: Surgical treatment of acetabular fracture has long been a challenging
      area in the field of orthopedic trauma. The aim of this research was to
      investigate the operative methods for delayed acetabular fractures and to assess
      the operation results. METHODS: The operative approaches, procedures, results,
      and complications of the delayed acetabular fractures between 1995 and 2005 were
      retrospectively evaluated at Beijing Jishuitan Hospital. Quality of life was
      assessed for each patient with the Merle d'Aubingne and Postel fracture function
      rating scale and the radiological result was assessed using the Matta
      radiological score. RESULTS: Sixty-eight cases (70 hips) were followed up with a
      minimal duration of five years (average of 5.8 years). Excellent functional
      results were observed in 10 hip joints, good results in 40, fair results in 11,
      and poor results in nine. The risks of poor prognosis include impact fracture or
      osteochondral fracture of femoral head, a time beyond 42 days from injury to
      operative management, and dislocation of femoral head during the injury. Some of
      the problems, which were observed included postoperative infection in two hips,
      iatrogenic sciatic nerve injury in eight hips, traumatic arthritis in 15 hips,
      heterotopic ossification in 17 hips, and necrosis of the femoral head in six
      hips. CONCLUSION: A careful selection of operative indications for delayed
      acetabular fractures in combination with a proper operative approach and
      appropriate reduction and fixation could guarantee relatively good results.

PMID- 23876900
TI  - Effect of c-Met inhibitor SU11274 on human colon cancer cell growth.
AB  - BACKGROUND: Colon cancer is one of the major malignancies worldwide and it still
      remains resistant to much of the currently available chemotherapy. Downregulation
      of HGF/c-Met signaling pathway is an emerging therapy for cancer treatment.
      METHODS: In this study, the inhibitory effects of c-Met phosphorylation were
      observed with SU11274 on different colon cancer cell lines in vitro. RESULTS: The
      results revealed the significant inhibitory effects of SU11274 on cell
      proliferation and cell survival, in a time and dose-dependent manner.
      Furthermore, the inhibitory effects of SU11274 on different subgroups of colon
      cancer cells via the HGF/c-Met signaling pathway were implicated in this study.
      CONCLUSION: The results suggested the possible selective therapeutic effects of c
      Met inhibitor on colon cancer.

PMID- 23876901
TI  - Reference intervals for common thyroid function tests, during different stages of
      pregnancy in Chinese women.
AB  - BACKGROUND: The importance of diagnosis of thyroid dysfunction during pregnancy
      has been widely recognized. Our study was designed to compare two different
      detection reagents between Abbott and Roche and to establish the gestational
      related reference intervals for thyroid function tests (TFT) in Chinese women and
      to assay the reference ranges with the American Thyroid Association recommended
      standard. METHODS: Serum samples were collected from 693 normal pregnant Chinese
      women and divided into five groups according to their gestational age: 9-13, 16
      20, 24-28, 32-34 and 37-40 weeks. Thyroid stimulating hormone (TSH) and free
      thyroxine (FT4) levels were determined by two different detection reagents:
      Abbott Architect I 2000 and Roche Cobas Elecsys 600. The reference ranges of the
      TFT indexes were calculated according to the National Academy of Clinical
      Biochemistry (NACB). The 2.5th and 97.5th percentiles of each stage were
      calculated, and the results were analyzed by one-way analysis of variances, t
      test, and Spearman correlation analysis. RESULTS: Thyroid hormone levels varied
      greatly among different gestational stages. TSH levels, as assessed via two
      different TSH ELISA kits showed consistent changing pattern during pregnancy and
      displayed linear correlation (P < 0.001). In 9-13 gestational weeks, TSH levels
      were significantly lower than that of other groups; and in 37-40 gestational
      weeks, it was higher than that of other groups (all P < 0.001). TSH reference
      ranges determined by Roche detection reagent in each group were higher than those
      by Abbott detection reagent (P < 0.01 respectively). FT4 levels were higher in 9
      13 gestational weeks than that of other groups (P < 0.001). FT4 levels determined
      by Roche reagent were higher than Abbott reagent in 9-13 weeks, (P < 0.001), and
      lower in 24-28 and 37-40 weeks (P < 0.001 and P = 0.016, respectively). The TSH
      level was correlated with FT4 levels in 9-13 gestational weeks by detection
      reagents (for Abbott reagent, r=-0.319 for FT4 P < 0.001; for Roche reagent, r=
      0.352 for FT4, P <0.001). CONCLUSION: Accurate evaluation of TFT in pregnant
      women should be based on the gestational-related reference intervals in Chinese
      population, and different detection reagents should also establish their own
      reference intervals.

PMID- 23876902
TI  - Factors influencing postoperative mortality one year after surgery for hip
      fracture in Chinese elderly population.
AB  - BACKGROUND: Disability and death following hip fracture is becoming more common
      as the population ages. Previous reports have focused on the selection of
      internal fixation methods and the analysis of the perioperative therapeutic
      results in the Chinese population. Few studies have focused on factors
      influencing medium and long term survival after surgery for hip fracture. We
      conducted a retrospective study on the factors influencing survival one year
      after hip fracture surgery in our elderly Chinese population to provide a
      reference for improved treatment and to enhance efficacy. METHODS: Records from
      patients undergoing treatment for hip fracture at our hospital from October 2009
      through June 2011 were retrospectively reviewed. Through telephone follow-up, the
      health condition of each patient was surveyed, and the 1-year postoperative
      mortality was analyzed. The patients' age, gender, fracture type, pre-injury
      health condition, mobility, complications, surgical timing, surgical types,
      methods of anesthesia, and postoperative complications were analyzed. Univariate
      and multivariate regression analysis was performed on relevant influencing
      factors. RESULTS: A total of 184 patients had complete data and were followed-up
      for 12-23 months (average, 16.5 months). There were 30 deaths (16.3%) at one
      year. Univariate analysis revealed that factors such as age, gender, fracture
      type, number of co-existing diseases, complications such as chronic obstructive
      pulmonary disease or sequelae of stroke, American society of Anesthesiology (ASA)
      scores, anesthesia methods, pre-injury activity, and post-operative complications
      were significantly different between survival versus mortality groups (P < 0.05).
      Multivariate regression analysis revealed that age, ASA score, pre-injury
      mobility and combined chronic obstructive pulmonary disease were independent risk
      factors for death. CONCLUSION: Full consideration of medium-/long-term risk
      factors in the treatment of hip fracture in the elderly, selection of appropriate
      anesthesia and treatment methods, and improved pre-surgical health conditions
      would reduce postoperative mortality and enhance surgical efficacy.

PMID- 23876903
TI  - Initial study of magnetic resonance diffusion tensor imaging in brain white
      matter of early AIDS patients.
AB  - BACKGROUND: HIV is a neurotropic virus which can cause brain white matter
      demyelination, gliosis, and other pathological changes that appear as HIV
      encephalitis or AIDS dementia. The purpose of this study was to investigate the
      change of the diffused condition of water molecules in brain white matter in
      early acquired immune deficiency syndrome (AIDS) patients using MR diffusion
      tensor imaging (DTI). METHODS: DTI examinations were performed on a Siemens 3.0T
      MR scanner in 23 AIDS patients with normal brain appearance by conventional MRI
      and 20 healthy volunteers as the control group. Fractional anisotropy (FA) and
      apparent diffusion coefficient (ADC) values were measured in nine regions; corpus
      callosum (CC) knee, CC body, CC splenium, periventricular white matter, frontal
      lobe white matter, parietal lobe white matter, occipital lobe white matter, and
      the anterior and posterior limbs of the internal capsule. The mean FA and ADC
      values from each region were compared in three groups: the symptomatic,
      asymptomatic and the control. RESULTS: The mean FA values were significantly
      lower and the mean ADC values were significantly higher in all nine regions in
      patients in the symptomatic group than in the asymptomatic and control group
      patients. In the asymptomatic group, the mean FA values were significantly lower
      and the mean ADC values were significantly higher at the CC knee, CC body, CC
      splenium, periventricular white matter, frontal lobe white matter and parietal
      lobe white matter, than in the control group. There were no significant
      differences at other regions between the two groups. CONCLUSIONS: The diffused
      changes of water molecules in brain white matter in AIDS patients are related to
      brain white matter regions. DTI examination can detect the brain white matter
      lesions early in AIDS patients.

PMID- 23876904
TI  - Significance of low serum vitamin D for infection risk, disease severity and
      mortality in critically ill patients.
AB  - BACKGROUND: Hospitalized patients often have higher rate of vitamin D deficiency
      than healthy people. Vitamin D levels below normal are associated with hospital
      stay, increased incidence of adverse prognosis and increased mortality of a
      number of diseases. Whether there is a relationship between vitamin D levels and
      infection or sepsis in the critically ill is still unclear. This study will
      explore the relationship between vitamin D levels and risk of infection,
      assessment for disease severity, and predictor of mortality. METHODS: To evaluate
      the value of vitamin D in intensive care unit (ICU) cases to sepsis, severity and
      prognosis assessment, high performance liquid chromatography and tandem mass
      spectrometry were used to measure the concentrations of vitamin D in sera of
      critically ill patients. The serum samples were drawn within the first 24 hours
      of ICU admission. RESULTS: The study included 206 people, 50 healthy controls, 51
      ICU control patients and 105 ICU diagnosed with sepsis. Critically ill ICU
      patients (ICU sepsis and ICU control group) had lower vitamin D concentration
      than normal people, but septic patients showed no significant reduction of
      vitamin D concentration when compared with critically ill patients with no
      positive etiological evidence. For assessment of disease severity, there were
      very low negative correlations between APACHE II, SAPS II and SOFA scores and
      vitamin D level. Additionally, patients of different 25-(OH)D levels showed no
      difference whether in terms of 28-day survival (X(2) = 1.78, P = 0.776) or 90-day
      survival (X(2) = 4.12, P = 0.389). Multivariate Logistic regression demonstrated
      that APECHE II and SAPS II scores were independent risk factors to deaths caused
      by sepsis. CONCLUSION: Clinically, serum concentration of vitamin D is not an
      indicator for diagnosis and assessment in critically ill patients
      (ClinicalTrial.gov identifier NCT01636232).

PMID- 23876905
TI  - Direct contact with bone marrow stromal cells promotes the invasions of SHI-1
      leukemia cells.
AB  - BACKGROUND: Interactions of tumor cells with the microenvironment were deemed to
      promote the tumor invasion and metastasis. CXC chemokine receptor 4 (CXCR4) and
      extracellular matrix metalloproteinase inducer (EMMPRIN) had reported to
      participate in this process. However the roles of bone marrow microenvironment in
      leukemic infiltration were not well investigated. METHODS: A co-culture system
      between SHI-1 cells and bone marrow stromal cells (BMSCs) is used to simulate the
      interactions of leukemic cells with their microenvironment. The trans-matrigel
      invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and
      SHI-1 cells were mixed in a ratio of 1:10 and added to the millicell chamber
      coated with matrigel. Either the co-culture supernatant or the functional
      blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion
      system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT
      PCR. The changes of the expression of matrix metalloproteinase-2, 9 (MMP-2, MMP
      9), tissue inhibitor of metalloproteinase 2 (TIMP-2), and CXCR4 mRNA in SHI-1
      cells were determined by real-time PCR. The concentration of stromal cell derived
      factor 1 (SDF-1) in serum free supernatant was measured by ELISA. RESULTS: Both
      SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the
      matrigel membrane; the coculture supernatant did not induce the invasion of SHI-1
      cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower
      chamber of millicell were significantly increased. The functional blocking
      peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered
      by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and
      TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a
      significantly higher level of SDF-1 in the co-cultured serum-free supernatant.
      CONCLUSION: The interactions of leukemic cells and BMSCs play important roles in
      leukemic cell infiltration.

PMID- 23876906
TI  - Neonatal pulse oximetry screening improves detecting of critical congenital heart
      disease.
AB  - OBJECTIVE: Life-threatening critical congenital heart disease (cCHD) is often not
      detected in the neonatal period. Unrecognized cCHD results in high morbidity and
      mortality rates. As a non-invasive, convenient, quick and accurate measuring
      method, pulse oximetry is considered to be a promising strategy to screen for
      cCHD in neonates. This article is a review on the neonatal pulse oximetry
      screening for cCHD. DATA SOURCES: Articles on neonatal pulse oximetry screening
      for cCHD were accessed from PubMed, using keywords including congenital heart
      defects, neonatal screening and oximetry. STUDY SELECTION: Original articles and
      critical reviews selected were relevant to the review's theme. RESULTS: The
      factors in the course of implementation, including threshold for positive pulse
      oximetry screening results, the pulse oximeters used, timing of the screening,
      and the measuring position, influence the accuracy of the screening. It is
      recommended that the screening is completed on the second day of life, before
      hospital discharge. Motion-tolerant pulse oximeters, which can also be applied to
      measure the saturation in low-perfusion conditions, should be used. The probe
      should be put on both the right hand and on one foot. Thresholds of < 95% in
      either limb or a difference of > 3% between the limbs as a positive result may be
      appropriate. It should be emphasized that pulse-oximetry screening cannot be used
      as the only way to detect cCHD, clinical examination is also important in this
      situation. Cost-benefit analysis in the United Kingdom revealed it was plausible
      to use pulse oximetry as an adjunct to clinical examination. However, it is still
      controversial as to whether pulse oximetry can be used as a routine screening
      method for cCHD in neonates. CONCLUSIONS: Neonatal pulse oximetry screening
      improves detection of cCHD. Further studies should be carried out before it
      becomes one of the routine newborn screening programs.

PMID- 23876907
TI  - Nuclear medical molecular imaging of tumor angiogenesis: current status and
      future prospects.
AB  - OBJECTIVE: To review the current status and progress on nuclear medical molecular
      imaging of angiogenesis. DATA SOURCES: A literature search was performed in
      Medline and PubMed published in English up to May 31, 2012. The search terms were
      molecular imaging, nuclear medicine and angiogenesis. STUDY SELECTION: Articles
      studying molecular imaging of angiogenesis using radionuclide were selected and
      reviewed. RESULTS: Molecular imaging has been used for studying angiogenesis by
      targeting integrin alphaVbeta3, VEGF/VEGFR, and matrix metalloproteinases (MMPs)
      with radionuclide-labeled tracers. The technology has been shown to be able to
      assess the angiogenesis status and/or predict the efficacy of anti-angiogenic
      therapy. Future directions of the research on the molecular imaging of
      angiogenesis include development of new tracers with better tumor targeting
      efficacy, desirable pharmacokinetics, and easy translation to clinical
      applications. CONCLUSION: Advances in molecular imaging of angiogenesis using
      radioculcide will make the technology a valuable tool for personalized anti
      angiogenesis treatment.

PMID- 23876908
TI  - Atrial fibrillation in Europe.

PMID- 23876909
TI  - Catheter ablation of atrial fibrillation.

PMID- 23876910
TI  - Current concepts and management of atrial fibrillation: the American perspective.

PMID- 23876911
TI  - A new medical safety factor for critical patients: emergency department
      overcrowding.

PMID- 23876912
TI  - Historical perspective of syphilis in the past 60 years in China: eliminated,
      forgotten, on the return.

PMID- 23876913
TI  - Enlightenment of German social health insurance system reform on China.

PMID- 23876914
TI  - Comparisons between diabetic and non-diabetic patients diagnosed with prostate
      cancer in China: a retrospective study.

PMID- 23876915
TI  - Assisted semen collection using two phosphodiesterase type 5 inhibitors
      (Tadalafil and Sildenafil) in infertile men with mild erectile dysfunction.

PMID- 23876916
TI  - Multi-detector computed tomography evaluation of tracheobronchial anomaly in
      pediatric patients with left pulmonary artery sling.

PMID- 23876917
TI  - Occult anomalous origin of the left coronary artery from the pulmonary artery
      with atrial septal defect initially visualized by transthoracic echocardiography.

PMID- 23876918
TI  - Aplasia cutis congenital: a case of large scalp and skull defects treated with
      conservative approach.

PMID- 23876919
TI  - Clinical features and surgical procedures of intradural-epidural and epidural
      cervical dumbbell tumors.

PMID- 23876920
TI  - Crohn's disease masked by median arcuate ligament syndrome.

PMID- 23876921
TI  - Successful pregnancy after amniotic fluid embolism.

PMID- 23876922
TI  - Transradial access should be preferred in all patients with acute coronary
      syndrome? The game is not yet over.

PMID- 23876923
TI  - Functional neuroimaging of the interference between working memory and the
      control of periodic ankle movement timing.
AB  - BACKGROUND: Limited information processing capacity in the brain necessitates
      task prioritisation and subsequent adaptive behavioural strategies for the dual
      task coordination of locomotion with severe concurrent cognitive loading.
      Commonly observed strategies include prioritisation of gait at the cost of
      reduced performance in the cognitive task. Alternatively alterations of gait
      parameters such as gait velocity have been reported presumably to free processing
      capacity for the benefit of performance in the cognitive task. The aim of this
      study was to describe the neuroanatomical correlates of adaptive behavioural
      strategies in cognitive-motor dual-tasking when the competition for information
      processing capacity is severe and may exceed individuals' capacity limitations.
      METHODS: During an fMRI experiment, 12 young adults performed slow continuous,
      auditorily paced bilateral anti-phase ankle dorsi-plantarflexion movements as an
      element of normal gait at .5 Hz in single and dual task modes. The secondary task
      involved a visual, alphabetic N-back task with presentation rate jittered around
      .7 Hz. The N-back task, which randomly occurred in 0-back or 2-back form, was
      modified into a silent counting task to avoid confounding motor responses at the
      cost of slightly increasing the task's general coordinative complexity.
      Participants' ankle movements were recorded using an optoelectronic motion
      capture system to derive kinematic parameters representing the stability of the
      movement timing and synchronization. Participants were instructed to perform both
      tasks as accurately as possible. RESULTS: Increased processing complexity in the
      dual-task 2-back condition led to significant changes in movement parameters such
      as the average inter-response interval, the coefficient of variation of absolute
      asynchrony and the standard deviation of peak angular velocity. A regions-of
      interest analysis indicated correlations between these parameters and local
      activations within the left inferior frontal gyrus (IFG) such that lower IFG
      activations coincided with performance decrements. CONCLUSIONS: Dual-task
      interference effects show that the production of periodically timed ankle
      movements, taken as modelling elements of the normal gait cycle, draws on higher
      level cognitive resources involved in working memory. The interference effect
      predominantly concerns the timing accuracy of the ankle movements. Reduced
      activations within regions of the left IFG, and in some respect also within the
      superior parietal lobule, were identified as one factor affecting the timing of
      periodic ankle movements resulting in involuntary 'hastening' during severe dual
      task working memory load. This 'hastening' phenomenon may be an expression of re
      automated locomotor control when higher-order cognitive processing capacity can
      no longer be allocated to the movements due to the demands of the cognitive task.
      The results of our study also propose the left IFG as a target region to improve
      performance during dual-task walking by techniques for non-invasive brain
      stimulation.

PMID- 23876924
TI  - Norovirus surveillance among callers to foodborne illness complaint hotline,
      Minnesota, USA, 2011-2013.
AB  - Norovirus is the leading cause of foodborne disease in the United States. During
      October 2011-January 2013, we conducted surveillance for norovirus infection in
      Minnesota among callers to a complaint-based foodborne illness hotline who
      reported diarrhea or vomiting. Of 241 complainants tested, 127 (52.7%) were
      positive for norovirus. 

PMID- 23876926
TI  - Between the idea and the reality: GP liaison in a rural setting.
AB  - OBJECTIVES: To describe the organisational, clinical and pragmatic features of a
      GP liaison service established by the Division of Mental Health in the Darling
      Downs Hospital and Health Service catchment to facilitate the care of rural
      patients and improve communication between primary and specialist care.
      CONCLUSIONS: The GP liaison service was created using funding from the
      Commonwealth STP initiative to provide weekly registrar clinics to primary care
      providers in the Darling Downs. The service was eagerly accepted by providers who
      saw patient benefits outweighing financial considerations. Expectations of a
      greater level of care than the assessment and advice provided reflects the large
      unmet need for mental health services in rural areas. GPs expressed enthusiasm
      for true collaborative care, such as case management overseen by the public
      mental health service but based at GP offices.

PMID- 23876925
TI  - A molecular mechanism for glaucoma: endoplasmic reticulum stress and the unfolded
      protein response.
AB  - Primary open angle glaucoma (POAG) is a common late-onset neurodegenerative
      disease. Ocular hypertension represents a major risk factor, but POAG etiology
      remains poorly understood. Some cases of early-onset congenital glaucoma and
      adult POAG are linked to mutations in myocilin, a secreted protein of poorly
      defined function. Transgenic overexpression of myocilin in Drosophila and
      experiments in mice and human populations implicate the unfolded protein response
      (UPR) in the pathogenesis of glaucoma. We postulate that compromised ability of
      the UPR to eliminate misfolded mutant or damaged proteins, including myocilin,
      causes endoplasmic reticulum stress, resulting in functional impairment of
      trabecular meshwork cells that regulate intraocular pressure. This mechanism of
      POAG is reminiscent of other age-dependent neurodegenerative diseases that
      involve accumulation of protein aggregates. 

PMID- 23876927
TI  - Micro-Raman spectroscopy and chemometrical analysis for the distinction of copper
      phthalocyanine polymorphs in paint layers.
AB  - In art analysis, copper phthalocyanine (CuPc) is often identified as an important
      pigment (PB15) in 20th century artworks. Raman spectroscopy is a very valuable
      technique for the detection of this pigment in paint systems. However, PB15 is
      used in different polymorphic forms and identification of the polymorph could
      retrieve information on the production process of the pigment at the moment.
      Raman spectroscopy, being a molecular spectroscopic method of analysis, is able
      to discriminate between polymorphs of crystals. However, in the case of PB15,
      spectral interpretation is not straightforward, and Raman data treatment requires
      some improvements concerning the PB15 polymorphic discrimination in paints. Here,
      Raman spectroscopy is combined with chemometrical analysis in order to develop a
      procedure allowing us to identify the PB15 crystalline structure in painted
      layers and in artworks. The results obtained by Linear Discriminant Analysis
      (LDA), using intensity ratios as variables, demonstrate the ability of this
      procedure to predict the crystalline structure of a PB15 pigment in unknown paint
      samples. 

PMID- 23876928
TI  - Some new [(thione)2Au(diamine)]Cl3 complexes: synthesis, spectroscopic
      characterization, computational and in vitro cytotoxic studies.
AB  - Recent advances in oncology are focused on developing new complexes of gold(III)
      with various ligands that show augmented anti-proliferative potential and reduced
      toxicity as compared to cis-platin. In this study, new Au(III) complexes of the
      type [(thione)2Au(diamine)]Cl3 are reported, where thione=1,3-imidazolidine-2
      thione (Imt), 1,3-Diazinane-2-thione (Diaz) and diamine=1,2-diaminoethane (en),
      1,3-diaminopropane (pn) or 1,4-diaminobutane (bn). The solid state IR as well as
      (13)C and (15)N NMR data indicate that Au(III) center is bonded via sulfur of
      thiocarbonyl SC site of the thiones and also chelated by the diamines from the
      trans side of coordinated thiones. Spectroscopic data are evaluated by
      comparisons with calculated data from the built and optimized structure by
      GAUSSIAN 09 at the RB3LYP level with LanL2DZ bases set. These new Au(III)
      complexes based on mixed thione and diamine ligands are very similar to the
      square planar structure of tetracoordinate [Au(en)2]Cl3complex. In this study,
      cytotoxicity data for these gold(III) complexes against C6 glioma cell lines are
      also reported, and the results indicate some complexes have cytotoxicity
      comparable to cis-platin. 

PMID- 23876929
TI  - Transcranial magnetic stimulation for refractory focal status epilepticus in the
      intensive care unit.
AB  - PURPOSE: To examine the efficacy and safety profile of antiepileptic repetitive
      transcranial magnetic stimulation (rTMS) for refractory status epilepticus (RSE)
      in the intensive care unit (ICU) setting. In addition, hypothetical concerns
      about electrical interference of rTMS with ICU equipment have been previously
      raised. METHODS: We describe two cases of RSE treated with rTMS in the ICU.
      RESULTS: In one case, rTMS contributed to decreased seizure frequency; in the
      second case, rTMS transiently decreased seizure frequency. In both cases, rTMS
      was safe and did not interfere with the functioning of the ICU equipment.
      CONCLUSION: rTMS is a potential therapy for RSE when conventional therapies have
      failed. Future studies should investigate the efficacy of various rTMS
      stimulation parameters, safety issues, and bioengineering considerations in the
      ICU setting.

PMID- 23876931
TI  - Isolation, identification, and phylogenetic analysis of two avian leukosis virus
      subgroup J strains associated with hemangioma and myeloid leukosis.
AB  - Cases of myeloid leukosis and hemangioma associated with avian leukosis virus
      subgroup J (ALV-J) are becoming more frequent in China in commercial layer
      chickens and breeders of egg-type chickens. In this study, two strains of ALV-J
      (SCAU11-H and SCAU11-XG) associated with hemangioma and myelocytoma were isolated
      from commercial broiler breeder animals in 2011. Their full-length proviral
      sequences were analyzed, revealing several unique genetic differences between the
      two isolates, and suggesting that the two viruses were derived from two distinct
      lineages. Strain SCAU11-H showed high sequence homology to early Chinese isolates
      associated with hemangioma, while strain SCAU11-XG was genetically closer to the
      prototype strain, HPRS-103. The complete genomic nucleotide sequences of SCAU11-H
      and SCAU11-XG were 7471 bp and 7727 bp in length, respectively. They shared 94.8%
      identity with each other, and had 94.0-96.8% nucleotide identity to ALV-J
      reference isolates. Homology analysis of the env, pol, and gag genes of the two
      isolates and other references strains showed that the gag and pol genes of the
      two viruses were more conserved than the env gene. In addition, the two isolates
      had significant deletions and substitutions in their 3'-UTR regions, compared to
      HPRS-103. These results suggest that the env gene and the 3'-UTR regions in these
      ALV-J isolates have evolved rapidly, and might be involved in the oncogenic
      spectrum of ALV-J. The results of this study contribute to our further study of
      the relationship between ALV integration patterns and multi-pathotypes associated
      with ALV-J.

PMID- 23876930
TI  - Time-kill behaviour against eight bacterial species and cytotoxicity of
      antibacterial monomers.
AB  - OBJECTIVES: The objectives of this study were to investigate: (1) the
      antibacterial activity of two antibacterial monomers, dimethylaminododecyl
      methacrylate (DMADDM) and dimethylammoniumethyl dimethacrylate (DMAEDM), against
      eight different species of oral pathogens for the first time; (2) the
      cytotoxicity of DMAEDM and DMADDM. METHODS: DMAEDM and DMADDM were synthesized by
      reacting a tertiary amine group with an organo-halide. Minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) against eight
      species of bacteria were tested. Time-kill determinations were performed to
      examine the bactericidal kinetics. Cytotoxicity of monomers on human gingival
      fibroblasts (HGF) was assessed using a methyl thiazolyltetrazolium assay and
      live/dead viability assay. RESULTS: DMADDM showed strong bactericidal activity
      against all bacteria, with MIC of 1.2-9.8MUg/mL. DMAEDM had MIC of 20-80mg/mL.
      Time-kill determinations indicated that DMADDM and DMAEDM had rapid killing
      effects against eight species of bacteria, and eliminated all bacteria in 30min
      at the concentration of 4-fold MBC. Median lethal concentration for DMADDM and
      DMAEDM was between 20 and 40MUg/mL, which was 20-fold higher than 1-2MUg/mL for
      BisGMA control. CONCLUSIONS: DMAEDM and DMADDM were tested in time-kill assay
      against eight species of oral bacteria for the first time. Both were effective in
      bacteria-inhibition, but DMADDM had a higher potency than DMAEDM. Different
      killing efficacy was found against different bacteria species. DMAEDM and DMADDM
      had much lower cytotoxicity than BisGMA. Therefore, DMADDM and DMAEDM are
      promising for use in bonding agents and other restorative/preventive materials to
      combat a variety of oral pathogens.

PMID- 23876932
TI  - Experimental infection of white-tailed deer (Odocoileus virginianus) with
      Northern European bluetongue virus serotype 8.
AB  - Bluetongue (BT) is an insect-transmitted, economically important disease of
      domestic and wild ruminants. Although only five of the 26 reported bluetongue
      virus (BTV) serotypes are considered endemic to the USA, 10 exotic serotypes have
      been isolated primarily in the southeastern region of the country since 1999. For
      an exotic BTV serotype to become endemic there must be susceptible animal species
      and competent vectors. In the USA, sheep and white-tailed deer (WTD) are the
      primary sentinel livestock and wildlife species, respectively. In 2006, BTV-8 was
      introduced into Northern Europe and subsequently overwintered, causing
      unprecedented livestock disease and mortality during the 2006-2007 vector
      seasons. To assess the risk of the European strain of BTV-8 to North American
      WTD, and understand the role they could play after a similar introduction, eight
      bluetongue-seronegative WTD were inoculated with BTV-8. Body temperatures and
      clinical signs were recorded daily. Blood samples were analyzed for BTV RNA with
      quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR),
      serum analyzed for BTV antibodies by cELISA, and tissues taken for histopathology
      and qRT-PCR. All eight deer became infected and developed moderate to severe
      clinical disease from days 8 to 15. Peak viremia was from day 7 to 10 with
      detectable titers through the end of the study (28 days) in most deer. Serum
      antibody was detected by day 6, peaked by day 10 and continued through day 28. We
      conclude that North American WTD are highly susceptible to BTV-8 and would act as
      clinical disease sentinels and amplifying hosts during an outbreak. 

PMID- 23876934
TI  - Reliability, validity, and sensitivity to change of the lower extremity
      functional scale in individuals affected by stroke.
AB  - OBJECTIVE: To investigate reliability, validity, and sensitivity to change of the
      Lower Extremity Functional Scale (LEFS) in individuals affected by stroke. The
      secondary objective was to test the validity and sensitivity of a single-item
      linear analog scale (LAS) of function. DESIGN: Prospective cohort reliability and
      validation study. SETTING: A single rehabilitation department in an academic
      medical center. PATIENTS: Forty-three individuals receiving neurorehabilitation
      for lower extremity dysfunction after stroke were studied. Their ages ranged from
      32 to 95 years, with a mean of 70 years; 77% were men. METHODS: Test-retest
      reliability was assessed by calculating the classical intraclass correlation
      coefficient, and the Bland-Altman limits of agreement. Validity was assessed by
      calculating the Pearson correlation coefficient between the instruments.
      Sensitivity to change was assessed by comparing baseline scores with end of
      treatment scores. Measurements were taken at baseline, after 1-3 days, and at 4
      and 8 weeks. MAIN OUTCOME MEASUREMENTS: The LEFS, Short-Form-36 Physical Function
      Scale, Berg Balance Scale, Six-Minute Walk Test, Five-Meter Walk Test, Timed Up
      and-Go test, and the LAS of function were used. RESULTS: The test-retest
      reliability of the LEFS was found to be excellent (ICC = 0.96). Correlated with
      the 6 other measures of function studied, the validity of the LEFS was found to
      be moderate to high (r = 0.40-0.71). Regarding the sensitivity to change, the
      mean LEFS scores from baseline to study end increased 1.2 SD and for LAS 1.1 SD.
      CONCLUSION: LEFS exhibits good reliability, validity, and sensitivity to change
      in patients with lower extremity impairments secondary to stroke. Therefore, the
      LEFS can be a clinically efficient outcome measure in the rehabilitation of
      patients with subacute stroke. The LAS is shown to be a time-saving and
      reasonable option to track changes in a patient's functional status.

PMID- 23876935
TI  - Autologous platelet-rich plasma versus dextrose prolotherapy for the treatment of
      chronic recalcitrant plantar fasciitis.
AB  - OBJECTIVE: To determine the efficacy of autologous platelet-rich plasma (PRP)
      compared with dextrose prolotherapy (DP) in patients with chronic recalcitrant
      plantar fasciitis (PF) DESIGN: A single-blinded, randomized, controlled study.
      SETTING: Department of Physical Medicine and Rehabilitation of a university
      hospital. PARTICIPANTS: Twenty-one patients with a clinical diagnosis of chronic
      PF confirmed by diagnostic ultrasound (plantar fascia thickness >4 mm) were
      randomly assigned to the PRP group (n = 10) or the DP group (n = 11).
      INTERVENTIONS: Each patient received 2 injections into the plantar fascia through
      a peppering technique under ultrasound guidance at an interval of 2 weeks, either
      with 2 mL of autologous PRP or 2 mL of 15% dextrose/lidocaine solution. MAIN
      OUTCOME MEASUREMENTS: The outcome measures included the pain, disability, and
      activity limitation subscales, measured by means of the Foot Functional Index.
      Data were collected before the first injection, at 2 weeks (before the second
      injection), and at the 2- and 6-month follow-ups. RESULTS: All patients completed
      the follow-ups, with the exception of 1 patient in the PRP group. The mean Foot
      Functional Index total and subcategory score improvements were greater in the PRP
      group compared with the DP group (improvement with PRP vs DP, total: 30.4% vs
      15.1%, pain: 29.7% vs 17.1%, disability: 26.6% vs 14.5%, activity limitation:
      28.0% vs 12.4%). However, no statistically significant difference was noted at
      any follow-up. In the pain and disability subcategories, both groups showed
      significant improvements at the last re-evaluation. The PRP group also showed
      significant improvements in the disability and activity limitation subscales at
      the second re-evaluation. CONCLUSIONS: Each treatment seems to be effective for
      chronic recalcitrant PF, expanding the treatment options for patients in whom
      conservative care has failed. PRP treatment also may lead to a better initial
      improvement in function compared with DP treatment.

PMID- 23876933
TI  - Characterization of Streptococcus suis serotype 2 isolates from China.
AB  - Streptococcus suis (S. suis) is a major pathogen in the pig industry and an
      important zoonotic agent that causes severe invasive diseases in humans. Previous
      studies based on multilocus sequence typing (MLST) and the associations between
      sequence types and genotypes or virulence suggested that North American S. suis
      serotype 2 isolates are composed of multiple populations. This study investigated
      the population structure of S. suis serotype 2 isolates in China. We constructed
      a phylogenetic tree for S. suis serotype 2 isolates based on 16S rRNA gene typing
      and MLST, studied associations between clades and sources, analyzed the genotype
      distributions of virulence markers [muramidase-released protein (MRP),
      extracellular protein factor (EF), and suilysin (SLY)] in different clades,
      computed the selection pressures for these virulence marker genes, and verified
      the associations between clades and virulence. There were two primary clades
      (populations) in the phylogenetic tree of S. suis serotype 2. The two populations
      were associated with different tissue tropisms. The genotypic distributions and
      selection pressures of MRP, EF, and SLY were different between the two
      populations, which suggested that they had different evolutionary paths. The two
      populations also displayed differences in virulence in experimentally infected
      mice. The results provide insights into the population structure of S. suis
      serotype 2 isolates in China and suggest that S. suis serotype 2 clade 1 is an
      overlooked population that deserves further evaluation. 

PMID- 23876936
TI  - A parallel G-quadruplex-selective luminescent probe for the detection of
      nanomolar calcium(II) ion.
AB  - A parallel G-quadruplex-selective iridium(III) complex has been synthesized and
      employed as a luminescent probe in a label-free G-quadruplex-based detection
      assay for Ca(2+) ions in aqueous solution. In this assay, a guanine-rich
      oligonucleotide (G4, 5'-G4T4G4-3') initially exists in an antiparallel G
      quadruplex conformation, resulting in a low luminescence signal. Upon incubation
      with Ca(2+) ions, the antiparallel G-quadruplex is induced into a parallel G
      quadruplex conformation, which greatly enhances the luminescence emission of the
      iridium(III) probe. This method was highly sensitive for Ca(2+) ions with a limit
      of detection in the nanomolar range, and was selective for Ca(2+) over other
      metal ions. 

PMID- 23876938
TI  - Study of biochemical biomarkers in freshwater prawn Macrobrachium borellii
      (Crustacea: Palaemonidae) exposed to organophosphate fenitrothion.
AB  - Several agrochemicals like organophosphates are extensively used to control pests
      in agricultural practices but they also adversely affect non-target fauna. The
      effect of organophosphorous fenitrothion on the prawn Macrobrachium borellii was
      evaluated. The 96-h LC50 was determined. Activity of superoxide dismutase,
      catalase, glutathione-S-transferase and lipid oxidation levels, were evaluated in
      the hepatopancreas from adults exposed to sublethal fenitrothion concentrations
      for 1, 2, 4 and 7 days. In addition, superoxide dismutase mRNA expression,
      acetylcholinesterase inhibition and haemocyte DNA damage were determined. The 96
      h LC50 was 4.24MUg/l of fenitrothion. Prawn exposed to sublethal FS
      concentrations showed an increase of both catalase and superoxide dismutase
      activities, mainly after 2 and 4 days exposure and an increase of glutathione-S
      transferase activity from day 2 to day 7 while lipid oxidation levels increased
      mainly on day 1. Superoxide dismutase transcripts were significantly higher in
      fenitrothion -treated prawns, indicating an induction mechanism. Hemolymph
      analysis showed that while acetylcholinesterase activity decreased after 2 days,
      haemocytes displayed most DNA damage after 7-day exposure to fenitrothion. These
      results indicate that prawn enzymes are highly sensitive to fenitrothion
      exposure, and these biological responses in M. borellii could be valuable
      biomarkers to monitor organophosphorous contamination in estuarine environments. 

PMID- 23876939
TI  - Analogy instruction and speech performance under psychological stress.
AB  - To examine the efficacy of explicit and implicit forms of instruction for speech
      motor performance under conditions of psychological stress. In experiment 1, 20
      participants were asked to deliver a formal presentation to validate the modified
      Trier Social Stress Test (TSST). In experiment 2, 40 participants were instructed
      explicitly by verbal explanation or implicitly by analogy to speak with minimum
      pitch variation and were subjected to psychological stress using the modified
      TSST. Acoustic correlates of pitch height (mean fundamental frequency) and pitch
      variation (standard deviation of fundamental frequency) significantly increased
      in experiment 1 when participants delivered a speech under modified TSST
      condition. In experiment 2, explicitly instructed participants were unable to
      maintain minimum pitch variation under psychological pressure caused by the
      modified TSST, whereas analogy-instructed participants maintained minimal pitch
      variation. The findings are consistent with existing evidence that analogy
      instructions may result in characteristics of implicit motor learning, such as
      greater stability of performance under pressure. Analogy instructions may
      therefore benefit speech motor performance and might provide a useful clinical
      tool for treatment of speech-disordered populations. 

PMID- 23876937
TI  - An HPLC-tandem mass spectrometry method for simultaneous detection of alkylated
      base excision repair products.
AB  - DNA glycosylases excise a broad spectrum of alkylated, oxidized, and deaminated
      nucleobases from DNA as the initial step in base excision repair. Substrate
      specificity and base excision activity are typically characterized by monitoring
      the release of modified nucleobases either from a genomic DNA substrate that has
      been treated with a modifying agent or from a synthetic oligonucleotide
      containing a defined lesion of interest. Detection of nucleobases from genomic
      DNA has traditionally involved HPLC separation and scintillation detection of
      radiolabeled nucleobases, which in the case of alkylation adducts can be
      laborious and costly. Here, we describe a mass spectrometry method to
      simultaneously detect and quantify multiple alkylpurine adducts released from
      genomic DNA that has been treated with N-methyl-N-nitrosourea (MNU). We
      illustrate the utility of this method by monitoring the excision of N3
      methyladenine (3 mA) and N7-methylguanine (7 mG) by a panel of previously
      characterized prokaryotic and eukaryotic alkylpurine DNA glycosylases, enabling a
      comparison of substrate specificity and enzyme activity by various methods.
      Detailed protocols for these methods, along with preparation of genomic and
      oligonucleotide alkyl-DNA substrates, are also described.

PMID- 23876940
TI  - Voice problems of group fitness instructors: diagnosis, treatment, perceived and
      experienced attitudes and expectations of the industry.
AB  - OBJECTIVES: To determine the anatomical and physiological nature of voice
      problems and their treatment in those group fitness instructors (GFIs) who have
      sought a medical diagnosis; the impact of voice disorders on quality of life and
      their contribution to activity limitations and participation restrictions; and
      the perceived attitudes and level of support from the industry at large in
      response to instructor's voice disorders and need for treatment. STUDY DESIGN:
      Prospective self-completion questionnaire design. METHODS: Thirty-eight
      individuals (3 males and 35 females) currently active in the Australian fitness
      industry who had been diagnosed with a voice disorder completed an online self
      completion questionnaire administered via SurveyMonkey. RESULTS: Laryngeal
      pathology included vocal fold nodules (N = 24), vocal fold cysts (N = 2), vocal
      fold hemorrhage (N = 1), and recurrent chronic laryngitis (N = 3). Eight
      individuals reported vocal strain and muscle tension dysphonia without concurrent
      vocal fold pathology. Treatment methods were variable, with 73.68% (N = 28)
      receiving voice therapy alone, 7.89% (N = 3) having voice therapy in combination
      with surgery, and 10.53% (N = 4) having voice therapy in conjunction with
      medication. Three individuals (7.89%) received no treatment for their voice
      disorder. During treatment, 82% of the cohort altered their teaching practices.
      Half of the cohort reported that their voice problems led to social withdrawal,
      decreased job satisfaction, and emotional distress. Greater than 65% also
      reported being dissatisfied with the level of industry and coworker support
      during the period of voice recovery. CONCLUSIONS: This study identifies that GFIs
      are susceptible to a number of voice disorders that impact their social and
      professional lives, and there is a need for more proactive training and advice on
      voice care for instructors, as well as those in management positions within the
      industry to address mixed approaches and opinions regarding the importance of
      voice care.

PMID- 23876941
TI  - Pitch and pitch variation in lesbian women.
AB  - OBJECTIVES: The purpose of this study was to investigate to what extent lesbian
      women demonstrate pitch and pitch variation that is different from that of
      heterosexual women. STUDY DESIGN: Static group comparison. METHODS: The average
      pitch and pitch variation of a group of 34 self-identified lesbian women and an
      age-matched group of 68 heterosexual women were compared. The speech sample
      consisted of read speech. Acoustic analysis was performed by means of PRAAT.
      RESULTS: Mean fundamental frequency in the group of lesbian women was
      significantly lower than that of the group of heterosexual women. The lesbian
      woman also showed significantly less pitch variation. CONCLUSIONS: Lesbian women
      tend to demonstrate a lower average pitch and less pitch variation than
      heterosexual women, but this does not mean a confirmation of the popular
      stereotype that lesbian women are masculine women. In their assessment of clients
      with voice disorders, clinicians should reckon with the sociophonetic variation
      that is associated with sexual orientation.

PMID- 23876942
TI  - Student training to perceptually assess severity of dysphonia using the dysphonic
      severity percentage scale.
AB  - OBJECTIVES/HYPOTHESIS: The goal of the present study was to determine if students
      can be trained to reliably perceive dysphonia using the Dysphonic Severity
      Percentage (DSP) scale, a perceptual measure shown to have high interrater
      reliability when used by speech-language pathologists experienced with voice
      disorders. Because the DSP scale was found to be useful as a research tool in the
      measurement of dysphonia, using it to train students to recognize dysphonia can
      enhance their education as future clinicians and researchers. METHODS: This
      method involved having five inexperienced speech-language pathology students
      listen to voice samples in two conditions (spontaneous speech and paragraph
      reading) of 10 clients with moderate to severe dysphonia (phonotrauma); the
      students simultaneously tallied the nondysphonic syllables on written content of
      the samples to obtain a DSP for both conditions. Because the clients' dysphonias
      were moderate to severe, and there were many dysphonic syllables, it was more
      efficient and advantageous for the students' perception and training to tally the
      nondysphonic syllables, leaving the dysphonic syllables to calculate the DSP. By
      tallying the nondysphonic syllables, the students were still recognizing which
      syllables were dysphonic by not choosing them, thus increasing their perception
      of both normal and disordered syllables. RESULTS AND CONCLUSION: Statistical
      analysis using the intraclass correlation coefficient revealed high interrater
      reliability and high correlations among the trained students for both spontaneous
      speech and paragraph reading, thus indicating similar training experiences and
      perceptions. This method appeared to be a more quantitative measure of perceptual
      ratings than current scales, which use general gradations of dysphonic severity.
      Moreover, the DSPs were similar between the newly trained students and
      experienced raters for spontaneous speech, indicating that the students could be
      trained in the direction experienced by voice clinicians. There was, however, a
      significant difference between the two groups for paragraph reading, which will
      be discussed. It was concluded that the DSP method was an effective technique to
      train students to recognize dysphonia.

PMID- 23876946
TI  - In adults: 47.2% have periodontitis! How about in orthodontic patients?
AB  - The occurrence of chronic inflammatory periodontal disease due to dental plaque
      in adults over 30 years of age was noticed in 47.2% of the 3,742 subjects
      studied, representing a 64.7 million people population in the 50 states of the
      U.S. and the District of Columbia. The methods used by the authors were uniquely
      precise and the results brought us to great insight on the correlation between
      orthodontic treatment and periodontal health, which is described below. 

PMID- 23876947
TI  - Angle Class II correction with MARA appliance.
AB  - OBJECTIVE: To assess the effects produced by the MARA appliance in the treatment
      of Angle's Class II, division 1 malocclusion. METHODS: The sample consisted of 44
      young patients divided into two groups: The MARA Group, with initial mean age of
      11.99 years, treated with the MARA appliance for an average period of 1.11 years,
      and the Control Group, with initial mean age of 11.63 years, monitored for a mean
      period of 1.18 years with no treatment. Lateral cephalograms were used to compare
      the groups using cephalometric variables in the initial and final phases. For
      these comparisons, Student's t test was employed. RESULTS: MARA appliance
      produced the following effects: Maxillary growth restriction, no change in
      mandibular development, improvement in maxillomandibular relationship, increased
      lower anterior facial height and counterclockwise rotation of the functional
      occlusal plane. In the upper arch, the incisors moved lingually and retruded,
      while the molars moved distally and tipped distally. In the lower arch, the
      incisors proclined and protruded, whereas the molars mesialized and tipped
      mesially. Finally, there was a significant reduction in overbite and overjet,
      with an obvious improvement in molar relationship. CONCLUSIONS: It was concluded
      that the MARA appliance proved effective in correcting Angle's Class II, division
      1 malocclusion while inducing skeletal changes and particularly dental changes.

PMID- 23876943
TI  - Protein C zymogen in adults with severe sepsis or septic shock.
AB  - INTRODUCTION: Activated protein C is associated with a risk of bleeding and its
      effects on survival in septic shock patients are questionable. Protein C zymogen
      has no risk of bleeding and improves the outcome of patients with septic shock.
      We hereby describe the largest published case series of adult patients receiving
      protein C zymogen. DESIGN, SETTING AND PARTICIPANTS: A prospective study on 23
      adult patients with severe sepsis or septic shock, two or more organ failures and
      at high risk for bleeding, treated with protein C zymogen (50IU/kg bolus followed
      by continuous infusion of 3IU/kg/h for 72h). RESULTS: The Z-test evidenced a
      significant reduction between the expected mortality (53%) and the observed
      mortality 30% (Z value=1.99, p=0.046) in our sample population. Protein C levels
      increased from 34+/-18% to 66+/-22% at 6h after PC bolus (p<0.001), and kept on
      increasing during 72h of administration (p<0.001 to baseline). Sequential Organ
      Failure Assessment (SOFA), score of organ dysfunction, decreased from baseline to
      7 days after administration of protein C from 14+/-2 to 7+/-4 (p<0.001). No
      adverse event drug related was noted. CONCLUSION: Protein C zymogen
      administration is safe and its use in septic patients should be investigated
      through a randomized controlled trial.

PMID- 23876948
TI  - Miniscrew-supported coil spring for molar uprighting: description.
AB  - INTRODUCTION: Since the beginning of miniscrews as orthodontic anchorage, many
      applications have been described in the literature. Among these, one is the
      uprighting of mesially inclined molars. In regard to the mechanical aspects,
      however, there is little information about the application of orthodontic forces
      using such devices. OBJECTIVE: The objective of this study was to describe a
      miniscrew supported spring for uprighting of mesially inclined molars. With this
      device, one can achieve the correct use of orthodontic biomechanics, thus
      favoring more predictable tooth movements and preventing unwanted movements from
      occurring.

PMID- 23876949
TI  - Correlation between transverse and vertical measurements in Brazilian growing
      patients, evaluated by Ricketts-Faltin frontal analysis.
AB  - INTRODUCTION: Currently in orthodontic diagnosis, besides the lateral
      cephalometric analysis which evaluates the anteroposterior and vertical
      direction, the frontal analysis may be added, leading us to another important
      dimension in space: the transverse dimension. OBJECTIVE: Few longitudinal samples
      with the frontal radiograph were published, so this cephalometric study was
      designed to correlate the transversal and vertical measures by Ricketts-Faltin
      frontal analysis into two radiographic times. METHODS: The sample consisted of 45
      Brazilian children, 25 girls and 20 boys, all presenting mixed dentition, with
      balanced facial aesthetics and no previous orthodontic/orthopedic treatment. The
      initial average age (T1) was 7.7 years and the final (T2) 13.3 years. The
      measurements evaluated were: FTD, MxTD, NTD, LITD, MdTD (transversal), OVD and
      TVD (vertical). RESULTS: All transversal measures were positively correlated with
      a medium or high correlation with each other and the vertical measurements; only
      LITD presented a low correlation with these measurements. CONCLUSIONS: It was
      concluded that the face has interdependent regions and that this feature remains
      with growth.

PMID- 23876950
TI  - In vitro evaluation of force degradation of elastomeric chains used in
      orthodontics.
AB  - OBJECTIVE: To analyze the in vitro force degradation of four different brands of
      elastomeric chains: American Orthodontics, Morelli, Ormco and TP Orthodontics.
      METHODS: The sample consisted of 80 gray elastomeric chains that were divided
      into four groups according to their respective manufacturers. Chain stretching
      was standardized at 21 mm with initial force release ranging from 300 g to 370 g.
      The samples were kept in artificial saliva at a constant temperature of 37
      degrees C and the degradation force was recorded at the following time intervals:
      initial, 1, 3, 5, 7 and 9 hours, and 1, 7, 14, 21, 28, and 35 days. RESULTS:
      There was a statistically significant difference between the groups regarding the
      force degradation, mainly within the first day, as a force loss of 50-55% was
      observed during that time in relation to the initial force. The force delivered
      at 35 days ranged from 122 g to 148 g. CONCLUSIONS: All groups showed force
      degradation over time, regardless of their trademarks, a force loss of 59-69% was
      observed in the first hour compared to baseline. However, because the variation
      in force degradation depends on the trademark, studies such as the present one
      are important for guiding the clinical use of these materials.

PMID- 23876951
TI  - Effect of saliva contamination on bond strength with a hydrophilic composite
      resin.
AB  - OBJECTIVE: To evaluate the influence of saliva contamination on the bond strength
      of metallic brackets bonded to enamel with hydrophilic resin composite. METHODS:
      Eighty premolars were randomly divided into 4 groups (n = 20) according to
      bonding material and contamination: G1) bonded with Transbond XT with no saliva
      contamination, G2) bonded with Transbond XT with saliva contamination, G3) bonded
      with Transbond Plus Color Change with no saliva contamination and G4) bonded with
      Transbond Plus Color Change with saliva contamination. The results were
      statistically analyzed (ANOVA/Tukey). RESULTS: The means and standard deviations
      (MPa) were: G1) 10.15 +/- 3.75; G2) 6.8 +/- 2.54; G3) 9.3 +/- 3.36; G4) 8.3 +/-
      2.95. The adhesive remnant index (ARI) ranged between 0 and 1 in G1 and G4. In G2
      there was a prevalence of score 0 and similar ARI distribution in G3.
      CONCLUSIONS: Saliva contamination reduced bond strength when Transbond XT
      hydrophobic resin composite was used. However, the hydrophilic resin Transbond
      Plus Color Change was not affected by the contamination.

PMID- 23876952
TI  - Comparative analysis of the anterior and posterior length and deflection angle of
      the cranial base, in individuals with facial Pattern I, II and III.
AB  - OBJECTIVE: This study evaluated the variations in the anterior cranial base (S
      N), posterior cranial base (S-Ba) and deflection of the cranial base (SNBa) among
      three different facial patterns (Pattern I, II and III). METHOD: A sample of 60
      lateral cephalometric radiographs of Brazilian Caucasian patients, both genders,
      between 8 and 17 years of age was selected. The sample was divided into 3 groups
      (Pattern I, II and III) of 20 individuals each. The inclusion criteria for each
      group were the ANB angle, Wits appraisal and the facial profile angle
      (G'.Sn.Pg'). To compare the mean values obtained from (SNBa, S-N, S-Ba) each
      group measures, the ANOVA test and Scheffe's Post-Hoc test were applied. RESULTS
      AND CONCLUSIONS: There was no statistically significant difference for the
      deflection angle of the cranial base among the different facial patterns
      (Patterns I, II and III). There was no significant difference for the measures of
      the anterior and posterior cranial base between the facial Patterns I and II. The
      mean values for S-Ba were lower in facial Pattern III with statistically
      significant difference. The mean values of S-N in the facial Pattern III were
      also reduced, but without showing statistically significant difference. This
      trend of lower values in the cranial base measurements would explain the
      maxillary deficiency and/or mandibular prognathism features that characterize the
      facial Pattern III.

PMID- 23876953
TI  - Periodontal evaluation of different toothbrushing techniques in patients with
      fixed orthodontic appliances.
AB  - INTRODUCTION: Plaque control is the major consensus during orthodontic treatment
      to prevent the occurrence of cavities and periodontal inflammation. The mechanic
      resource of greater effectiveness and frequent use in this control is the oral
      hygiene. The tooth brushing techniques most used in orthodontic patients are:
      Ramfjord's method, Modified Stillman technique and Bass method. OBJECTIVE: Since
      control studies evaluating the effectiveness of usual tooth brushing techniques
      do not show clear advantage, the objective of this study was to evaluate the
      effectiveness of three brushing methods, through periodontal clinical parameters
      of patients with fixed orthodontic appliances. METHODS: Thirty patients were
      selected, with ages between 14 and 22 years old, with fixed orthodontic
      appliances. After basic periodontal treatment the following factors were
      evaluated: 1--Plaque index and 2--Gingival index and each patient was randomly
      included in one of the three selected groups according to the brushing technique:
      Group 1--Scrubbing technique; Group 2--Modified Stillman technique and Group 3-
      Bass technique. Patients were evaluated for 9 months. RESULTS: The results showed
      a significant reduction of clinical parameters by the end of this period, however
      there was a very significant reduction of Gingival index on group 3 (13.6%) when
      compared to the other groups. CONCLUSION: Thus, it can be suggested that the Bass
      technique can be effective on the reduction of periodontal clinical parameters of
      Plaque index and Gingival index in patients with fixed orthodontic appliances.

PMID- 23876954
TI  - Does self-ligating brackets type influence the hysteresis, activation and
      deactivation forces of superelastic NiTi archwires?
AB  - OBJECTIVE: To compare hysteresis, activation and deactivation forces produced by
      first-order deformation of Contour 0.014-in NiTi wire (Aditek, Brazil) in four
      brands of self-ligating brackets: Damon MX, Easy Clip, Smart Clip and In-Ovation.
      METHODS: Activation and deactivation forces were measured in an Instron universal
      tensile machine at 3 mm/minute speed to a total displacement of 4 mm. Tests were
      repeated eight times for each bracket/wire combination. Statistical analysis
      comprised ANOVA and Tukey's multiple comparisons test. RESULTS: Using a 4-mm
      deformation, mean activation forces increased in the following order: Damon = 222
      gf, Easy Clip = 228 gf, In-Ovation = 240 gf and Smart Clip = 306 gf. The same
      order was observed for mean hysteresis values, i.e., 128 gf, 140 gf, 150 gf and
      206 gf, respectively. The respective values of deactivation forces for the Damon,
      Easy Clip, In-Ovation and Smart Clip brackets were 94 gf, 88 gf, 90 gf and 100
      gf. CONCLUSIONS: Brackets with higher activation forces were accompanied by
      higher hysteresis values, which resulted in clinically similar deactivation
      forces, regardless of the type of self-ligating brackets used.

PMID- 23876955
TI  - Evaluation of ionic degradation and slot corrosion of metallic brackets by the
      action of different dentifrices.
AB  - OBJECTIVE: To evaluate the in vitro ionic degradation and slot base corrosion of
      metallic brackets subjected to brushing with dentifrices, through analysis of
      chemical composition by Energy Dispersive Spectroscopy (EDS) and qualitative
      analysis by Scanning Electron Microscopy (SEM). METHODS: Thirty eight brackets
      were selected and randomly divided into four experimental groups (n = 7). Two
      groups (n = 5) worked as positive and negative controls. Simulated orthodontic
      braces were assembled using 0.019 x 0.025-in stainless steel wires and
      elastomeric rings. The groups were divided according to surface treatment: G1
      (Maxima Protecao Anticaries(r)); G2 (Total 12(r)); G3 (Sensitive(r)); G4
      (Branqueador(r)); Positive control (artificial saliva) and Negative control (no
      treatment). Twenty eight brushing cycles were performed and evaluations were made
      before (T0) and after (T1) experiment. RESULTS: The Wilcoxon test showed no
      difference in ionic concentrations of titanium (Ti), chromium (Cr), iron (Fe) and
      nickel (Ni) between groups. G2 presented significant reduction (p < 0.05) in the
      concentration of aluminium ion (Al). Groups G3 and G4 presented significant
      increase (p < 0.05) in the concentration of aluminium ion. The SEM analysis
      showed increased characteristics indicative of corrosion on groups G2, G3 and G4.
      CONCLUSION: The EDS analysis revealed that control groups and G1 did not suffer
      alterations on the chemical composition. G2 presented degradation in the amount
      of Al ion. G3 and G4 suffered increase in the concentration of Al. The immersion
      in artificial saliva and the dentifrice Maxima Protecao Anticaries(r) did not
      alter the surface polishing. The dentifrices Total 12(r), Sensitive(r) and
      Branqueador(r) altered the surface polishing.

PMID- 23876956
TI  - Influence of intentional ankylosis of deciduous canines to reinforce the
      anchorage for maxillary protraction.
AB  - INTRODUCTION: This retrospective cephalometric study analyzed the influence of
      intentional ankylosis of deciduous canines in patients with Class III
      malocclusion and anterior crossbite, in the deciduous and early mixed dentition
      stages, treated by orthopedic maxillary expansion followed by maxillary
      protraction. METHODS: Lateral cephalograms of 40 patients were used, divided in 2
      groups paired for age and gender. The Ankylosis Group was composed of 20 patients
      (10 boys and 10 girls) treated with induced ankylosis and presenting initial and
      final mean ages of 7 years 4 months and 8 years 3 months, respectively, with a
      mean period of maxillary protraction of 11 months. The Control Group comprised 20
      patients (10 boys and 10 girls) treated without induced ankylosis, with initial
      and final mean ages of 7 years 8 months and 8 years 7 months, respectively, with
      a mean period of maxillary protraction of 11 months. Two-way analysis of variance
      and covariance analysis were applied to compare the initial and final
      cephalometric variables and the treatment changes between groups. RESULTS:
      According to the results, the variables evidencing the significant treatment
      changes between groups confirmed that the intentional ankylosis enhanced the
      sagittal response of the apical bases (Pg-NPerp) and increased the facial
      convexity angles (NAP and ANB). CONCLUSIONS: The protocol involving intentional
      ankylosis of deciduous canines enhanced the sagittal response of the apical
      bases.

PMID- 23876957
TI  - Orthodontic treatment need for Brazilian schoolchildren: a study using the Dental
      Aesthetic Index.
AB  - OBJECTIVE: To determine the normative orthodontic treatment need among 12-year
      old Brazilian schoolchildren, in the municipality of Juiz de Fora, Minas Gerais,
      Brazil, and compare with the need as perceived by the children themselves and
      their parents or caregivers, assessing putative associated sociodemographic
      factors. METHODS: Four hundred and fifty one children without a previous history
      of orthodontic treatment were randomly selected from a population of 7,993
      schoolchildren regularly attending the public and private educational sectors of
      the municipality of Juiz de Fora, Minas Gerais, Brazil. RESULTS: The prevalence
      of normative orthodontic treatment need in 12-year-old children, assessed with
      the Dental Aesthetic Index (DAI) was 65.6% (n = 155). The need perceived by the
      caregivers was 85.6%, and by the children was 83.8%. Only the perception by the
      caregivers maintained a significant correlation with the normative need of
      treatment when adjusted to the parents' schooling and economical level (p =
      0.023). CONCLUSIONS: There is a high prevalence (65.6%) of malocclusion requiring
      orthodontic treatment in 12-year-old Brazilian schoolchildren. The most prevalent
      malocclusions in the study were: Crowding, Class II molar relationship and
      increased overjet. There was no significant correlation between the Index of
      Orthodontic Treatment Need - Aesthetic Component (IOTN-AC) related to dental
      aesthetic perception and the normative treatment need assessed with the DAI.

PMID- 23876958
TI  - Predisposing factors to severe external root resorption associated to orthodontic
      treatment.
AB  - OBJECTIVE: The aim of this study was to evaluate predisposing factors among
      patients who developed moderate or severe external root resorption (Malmgren's
      grades 3 and 4), on the maxillary incisors, during fixed orthodontic treatment in
      the permanent dentition. METHODS: Ninety-nine patients who underwent orthodontic
      treatment with fixed edgewise appliances were selected. Patients were divided
      into two groups: G1 - 50 patients with no root resorption or presenting only
      apical irregularities (Malmgren's grades 0 and 1) at the end of the treatment,
      with mean initial age of 16.79 years and mean treatment time of 3.21 years; G2 -
      49 patients presenting moderate or severe root resorption (Malmgren's grades 3
      and 4) at the end of treatment on the maxillary incisors, with mean initial age
      of 19.92 years and mean treatment time of 3.98 years. Periapical radiographs and
      lateral cephalograms were evaluated. Factors that could influence the occurrence
      of severe root resorption were also recorded. Statistical analysis included chi
      square tests, Fisher's exact test and independent t tests. RESULTS: The results
      demonstrated significant difference between the groups for the variables:
      Extractions, initial degree of root resorption, root length and crown/root ratio
      at the beginning, and cortical thickness of the alveolar bone. CONCLUSION: It can
      be concluded that: Presence of root resorption before the beginning of treatment,
      extractions, reduced root length, decreased crown/root ratio and thin alveolar
      bone represent risk factors for severe root resorption in maxillary incisors
      during orthodontic treatment.

PMID- 23876959
TI  - Evaluation of the friction force generated by monocristalyne and policristalyne
      ceramic brackets in sliding mechanics.
AB  - OBJECTIVE: To evaluate and compare "in vitro" the maximum friction force
      generated by three types of esthetic brackets, two types of polycrystalline
      conventional ceramic brackets (20/40 and InVu) and one type of sapphire
      monocrystalline bracket (Radiance) in dry and artificial saliva wet settings.
      Also, to evaluate the influence exerted by artificial saliva on the friction
      forces of those brackets. METHODS: Tests were performed in dry and artificial
      saliva wet setting (Oral Balance) by using an EMIC DL 10000 testing machine,
      simulating a 2 mm slide of 0.019 x 0.025-in rectangular stainless steel wires
      over the pre-angulated and pre-torqued (right superior canine, Roth prescription,
      slot 0.022 x 0.030-in) brackets (n = 18 for each bracket). In order to compare
      groups in dry and wet settings, the ANOVA was used. For comparisons related to
      the dry versus wet setting, the student t test was used for each group. RESULTS:
      The results showed that in the absence of saliva the Radiance monocrystalline
      brackets showed the highest friction coefficients, followed by the 20/40 and the
      InVu polycrystalline brackets. In tests with artificial saliva, the Radiance and
      the 20/40 brackets had statistically similar friction coefficients and both were
      greater than that presented by the InVu brackets. The artificial saliva did not
      change the maximum friction force of the Radiance brackets, but, for the others
      (20/40 and InVu), an increase of friction was observed in its presence.
      CONCLUSION: The InVu brackets showed, in the absence and in the presence of
      saliva, the lowest friction coefficient.

PMID- 23876960
TI  - Comparison of space analysis performed on plaster vs. digital dental casts
      applying Tanaka and Johnston's equation.
AB  - OBJECTIVE: The purpose of this study was to compare dental size measurements,
      their reproducibility and the application of Tanaka and Johnston regression
      equation in predicting the size of canines and premolars on plaster and digital
      dental casts. METHODS: Thirty plaster casts were scanned and digitized.
      Mesiodistal measurements of the teeth were then performed with a digital caliper
      on the plaster and digital casts using O3d software system (Widialabs(c)).The sum
      of the sizes of the lower incisors was used to obtain predictive values of the
      sizes of the premolars and canines using the regression equation, and these
      values were compared with the actual sizes of the teeth. The data were
      statistically analyzed by applying to the results Pearson's correlation test,
      Dahlberg's formula, paired t-test and analysis of variance (p < 0.05). RESULTS:
      Excellent intraexaminer agreement was observed in the measurements performed on
      both dental casts. No random error was present in the measurements obtained with
      the caliper and systematic error (bias) was more frequent in the digital casts.
      Space prediction obtained by applying the regression equation was greater than
      the sum of the canines and premolars on the plaster and digital casts.
      CONCLUSIONS: Despite an adequate reproducibility of the measurements performed on
      both casts, most measurements on the digital casts were higher than those on the
      plaster casts. The predicted space was overestimated in both models and
      significantly higher in the digital casts.

PMID- 23876961
TI  - Mini-implants: mechanical resource for molars uprighting.
AB  - INTRODUCTION: The early orthodontic treatment allows correction of skeletal
      discrepancies by growth control, and the elimination of deleterious habits, which
      are risk factors for the development of malocclusions, favoring for the
      correction of tooth positioning later in a second treatment stage. During
      development of teeth and occlusion, the mandibular second molars commonly erupt
      in the oral cavity after all other teeth of the anterior region. In their
      eruptive process there may be a condition known as tooth impaction, which
      precludes its complete eruption and requires proper uprighting treatment. The
      temporary anchorage devices allow disimpaction and movement of these teeth
      directly to their final position, without the need of patient compliance or
      reaction movements in other parts of the arch. OBJECTIVE: This paper aims at
      describing a case report of the treatment of a patient with Angle Class II
      malocclusion, performed in two phases, in which mini-implants were used for
      uprighting the impacted mandibular second molars.

PMID- 23876962
TI  - Surgical treatment of dental and skeletal Class III malocclusion.
AB  - Orthodontic preparation for surgical treatment of skeletal Class III malocclusion
      involves joint planning with an oral and maxillofacial surgeon to address the
      functional and esthetic needs of the patient. In order to allow surgical
      manipulation of the jaws in the preoperative phase, the need to achieve a
      negative overjet through incisor decompensation often leads the orthodontist to
      extract the upper first premolars. This report illustrates an orthodontic
      preparation case where due to specific factors inherent in the patient's
      psychological makeup retroclination of the upper incisors and proclination of the
      mandibular incisors was achieved without removing any teeth. This case was
      presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO) in
      partial fulfillment of the requirements for obtaining the BBO Diploma. 

PMID- 23876963
TI  - Relationship between temporomandibular disorders and orthodontic treatment: a
      literature review.
AB  - OBJECTIVE: The objective of this study was to review the most recent studies from
      the last 15 years, in search of clinical studies that report the relationship
      between TMD and orthodontic treatment and/or malocclusion. Our intention was to
      determine whether orthodontic treatment would increase the incidence of signs and
      symptoms of TMD, and whether orthodontic treatment would be recommended for
      treating or preventing signs and symptoms of TMD. METHODS: Literature reviews,
      editorials, letters to the editor, experimental studies in animals and short
      communications were excluded from this review. Were included only prospective,
      longitudinal, case-control or retrospective studies with a large sample and
      significant statistical analysis. Studies that dealt with craniofacial
      deformities and syndromes or orthognathic surgery treatment were also excluded,
      as well as those that reported only the association between malocclusion and TMD.
      RESULTS: There were 20 articles relating orthodontics to TMD according to the
      inclusion criteria. The studies that associated signs and symptoms of TMD to
      orthodontic treatment showed discrepant results. Some have found positive effects
      of orthodontic treatment on signs and symptoms of TMD, however, none showed a
      statistically significant difference. CONCLUSIONS: All studies cited in this
      literature review reported that orthodontic treatment did not provide risk to the
      development of signs and symptoms of TMD, regardless of the technique used for
      treatment, the extraction or non-extraction of premolars and the type of
      malocclusion previously presented by the patient. Some studies with long-term
      follow-up concluded that orthodontic treatment would not be preventive or a
      treatment option for TMD.

PMID- 23876964
TI  - Association of breastfeeding, pacifier use, breathing pattern and malocclusions
      in preschoolers.
AB  - OBJECTIVE: To evaluate the association of breastfeeding duration, pacifier use
      and nasal air flow with occlusal disorders among children. METHODS: This cross
      sectional observational study included 138 children aged 4 and 5 years selected
      in all the daycare centers of the city of Campo Limpo Paulista, Brazil.
      Questionnaires were applied to mothers to identify total duration of exclusive
      breastfeeding and non-nutritive sucking. The independent variables were: Sucking
      (pacifier, bottle, finger), breastfeeding duration and nasal air flow. The
      dependent variables were: Open bite, crossbite, overjet, overbite, diastema and
      maxillary deficiency. Frequency distribution calculations were performed, a chi
      square test, the Fisher exact test and, after that, stepwise logistic regression
      were used for statistical analysis, and the level of significance was set at 5%.
      RESULTS: The use of a pacifier was the most deleterious factor and increased
      chances of having open bite in 33.3 times, marked overjet in 2.77 times and
      posterior crossbite in 5.26 times. CONCLUSION: There was a significant
      association between non-nutritive sucking, particularly the use of a pacifier,
      and occlusal disorders. These findings are important to plan the treatment of
      preschoolers.

PMID- 23876965
TI  - Halogen light versus LED for bracket bonding: shear bond strength.
AB  - INTRODUCTION: LED light-curing devices seek to provide a cold light activator
      which allows protocols of material polymerization with shorter duration.
      OBJECTIVE: The present study aimed to evaluate the shear bond strength of bracket
      bonding using three types of light-curing devices: One with halogen light
      (Optilight Plus - Gnatus) and two with LEDs (Optilight CL - Gnatus and Elipar
      Freelight - 3M/ESPE). RESULTS: Comparing the results by analysis of variance, the
      Gnatus LED device showed an inferior statistical behavior in relation to other
      light sources, when activated by a short time. But, when it was used for 40
      seconds, the polymerization results were consistent with the other evaluated
      sources. The device with the best average performance was the halogen light,
      followed by the 3M/ESPE LED. CONCLUSION: It was concluded that the LEDs may be
      indicated in orthodontic practice, as long as a protocol is used for the
      application of light with the activation time of 40 seconds.

PMID- 23876966
TI  - Profile of the orthodontist practicing in the State of Sao Paulo--part 2.
AB  - INTRODUCTION: The choice of brackets, bands and wires is a very important aspect
      of orthodontic treatment. Stainless steel prevailed for a long time, but new
      alloys and resources have emerged to diversify the orthodontic wire mechanics.
      OBJECTIVE: This study aimed to investigate the profile and materials used by
      orthodontists practicing in the State of Sao Paulo, Brazil. METHODS: A
      questionnaire was sent to 2,414 specialists in Orthodontics and Dentofacial
      Orthopedics registered with the Regional Board of Dentistry of Sao Paulo State
      (CRO-SP). To assess the association between qualitative variables, the Chi-square
      association test was employed at 5% significance level. RESULTS: Five hundred and
      ninety-three (24.65%) questionnaires were completed and sent back. Efficiency was
      the key reason given by the professionals for choosing a particular material. The
      majority showed a preference for metal brackets (98%), followed by ceramics (32%)
      and polycarbonate (7.8%). The most widely used brackets had 0.022 x 0.028-in
      slots (73.2%). Regarding orthodontic wires, 88.2% employed round steel wires and
      conventional round NiTi wires, while 52.6% used round heat-activated NiTi and
      46.5% rectangular TMA wires. Elastics (92.9%) were the most widely used method to
      tie the orthodontic archwire to the bracket. CONCLUSIONS: In this survey, the
      orthodontists claimed that efficiency was the major motivator for choosing
      orthodontic materials. Conventional brackets tied with conventional elastic
      ligatures are still the most used by the professionals. Among steel and
      conventional Nitinol wires, round wires ranked first. The use of resources
      recently available to Brazilian orthodontists, such as self-ligating brackets and
      mini-implants, was not significant.

PMID- 23876967
TI  - Evaluation of two protocols for low-level laser application in patients submitted
      to orthodontic treatment.
AB  - INTRODUCTION: Different low-level laser (LLL) irradiation protocols have been
      tested to accelerate orthodontic tooth movement (OTM). Nevertheless, divergent
      results have been obtained. It was suggested that the stimulatory action of low
      level laser irradiation occurs during the proliferation and differentiation
      stages of bone cellular precursors, but not during later stages. OBJECTIVE: The
      purpose of this study was to determine the effect of two protocols of LLL
      irradiation on experimental tooth movement: One with daily irradiations and
      another with irradiations during the early stages. METHODS: Thirty-six rats were
      divided into control groups (CG1, CG2, CG3) and irradiated groups (IrG1, IrG2,
      IrG3) according to the presence of: experimental tooth movement, laser
      irradiation, type of laser irradiation protocol and date of euthanasia (3th or
      8th day of experiment). At the end of experimental periods, a quantitative
      evaluation of the amount of OTM was made and the reactions of the periodontium
      were analyzed by describing cellular and tissue reactions and by counting blood
      vessels. RESULTS: The amount of OTM revealed no significant differences between
      groups in the same experimental period (p < 0.05). Qualitative analysis revealed
      the strongest resorption activity in irradiated groups after seven days,
      especially when using the daily irradiation protocol. There was a higher number
      of blood vessels in irradiated animals than in animals without orthodontic
      devices and without laser irradiation (p < 0.05). CONCLUSION: Moreover,
      angiogenesis was verified in some of the irradiated groups. The irradiation
      protocols tested were not able to accelerate OTM and root resorption was observed
      while they were applied.

PMID- 23876968
TI  - Occlusal characteristics and orthodontic treatment need in black adolescents in
      Salvador/BA (Brazil): an epidemiologic study using the Dental Aesthetics Index.
AB  - OBJECTIVE: The objective of this article is to evaluate the need of orthodontic
      treatment, prevalence and severity of the malocclusions in individuals of black
      ethnicity in a representative sample of schoolchildren of the city of
      Salvador/Brazil, as well as to verify if the malocclusion was affected by socio
      demographic conditions such as age and gender. METHODS: The reference population
      was constituted of schoolchildren with age between 12 and 15 years, enrolled in
      public and private schools. The malocclusion was evaluated in 486 students of
      black ethnicity, with ages varying from 12 to 15 years, selected in random sample
      in multiple stages. The adopted significance level was 1% and the power of the
      test was 90%. A questionnaire registering demographic characteristics was filled
      out by each individual. The Dental Aesthetics Index (DAI) was used by previously
      calibrated examiners (kappa 0.89), according to criteria of the World Health
      Organization. RESULTS: It was verified that most of the individuals (76%) had
      little or any need for orthodontic treatment. About 24% showed a condition of
      severe malocclusion, culminating in a vital need for orthodontic treatment. The
      main occlusal characteristics found in the group with high need of orthodontic
      treatment were dental crowding and accentuated overjet. The age was positively
      related to the improvement of the maxillary overjet and to the presence of
      crowding. CONCLUSION: The development of public politics that aim the insertion
      of orthodontic treatment among the procedures of health programs, with the
      implementation and development of specialized centers, is fundamental.

PMID- 23876969
TI  - An epidermal equivalent assay for identification and ranking potency of contact
      sensitizers.
AB  - The purpose of this study was to explore the possibility of combining the
      epidermal equivalent (EE) potency assay with the assay which assesses release of
      interleukin-18 (IL-18) to provide a single test for identification and
      classification of skin sensitizing chemicals, including chemicals of low water
      solubility or stability. A protocol was developed using different 3D-epidermal
      models including in house VUMC model, epiCS(r) (previously EST1000TM), MatTek
      EpiDermTM and SkinEthicTM RHE and also the impact of different vehicles
      (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following
      topical exposure for 24h to 17 contact allergens and 13 non-sensitizers a robust
      increase in IL-18 release was observed only after exposure to contact allergens.
      A putative prediction model is proposed from data obtained from two laboratories
      yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which
      assesses the chemical concentration which results in 50% cytotoxicity (EE-EC50)
      with human and animal data showed a superior correlation with human DSA05
      (MUg/cm(2)) data (Spearman r=0.8500; P value (two-tailed)=0.0061) compared to
      LLNA data (Spearman r=0.5968; P value (two-tailed)=0.0542). DSA05=induction dose
      per skin area that produces a positive response in 5% of the tested population
      Also a good correlation was observed for release of IL-18 (SI-2) into culture
      supernatants with human DSA05 data (Spearman r=0.8333; P value (two
      tailed)=0.0154). This easily transferable human in vitro assay appears to be very
      promising, but additional testing of a larger chemical set with the different EE
      models is required to fully evaluate the utility of this assay and to establish a
      definitive prediction model. 

PMID- 23876970
TI  - FT-IR/ATR univariate and multivariate calibration models for in situ monitoring
      of sugars in complex microalgal culture media.
AB  - The objective of this work is to develop a quick and simple method for the in
      situ monitoring of sugars in biological cultures. A new technology based on
      Attenuated Total Reflectance-Fourier Transform Infrared (FT-IR/ATR) spectroscopy
      in combination with an external light guiding fiber probe was tested, first to
      build predictive models from solutions of pure sugars, and secondly to use those
      models to monitor the sugars in the complex culture medium of mixotrophic
      microalgae. Quantification results from the univariate model were correlated with
      the total dissolved solids content (R(2)=0.74). A vector normalized multivariate
      model was used to proportionally quantify the different sugars present in the
      complex culture medium and showed a predictive accuracy of >90% for sugars
      representing >20% of the total. This method offers an alternative to conventional
      sugar monitoring assays and could be used at-line or on-line in commercial scale
      production systems. 

PMID- 23876971
TI  - Effectiveness of indometacin to prevent ovulation in modified natural-cycle IVF:
      a randomized controlled trial.
AB  - Modified natural-cycle IVF has a lower pregnancy rate per started cycle as
      compared with IVF with ovarian stimulation due to, for example, premature
      ovulation. Indometacin administered before ovulation prevents follicle rupture.
      Therefore, addition of indometacin may improve the effectiveness of modified
      natural-cycle IVF. This double-blind, randomized, placebo-controlled trial with
      indometacin or placebo in 120 women aged 27-36 years compared the number of
      patients without premature ovulation as compared with the number of patients with
      one or more ovulations in a maximum of six cycles. Indometacin had no significant
      influence on the probability of a premature ovulation in patients during the six
      cycles (OR 2.38, 95% CI 0.94-6.04). A subgroup analysis showed a significant
      influence of indometacin in decreasing the probability of a premature ovulation
      in cycles without LH surge at the day of human chorionic gonadotrophin
      administration (OR 8.29, 95% CI 1.63-42.3, P=0.009). Although this study could
      not detect a significantly lower ovulation rate in the indometacin group versus
      the placebo group, the data suggest that a subgroup of patients without LH surge
      prior to oocyte retrieval might benefit from indometacin in modified natural
      cycle IVF.

PMID- 23876972
TI  - Replication study of RAD54B and GREB1 polymorphisms and risk of PCOS in Han
      Chinese.
AB  - A previous genome-wide association study (GWAS) of polycystic ovary syndrome
      (PCOS) identified several susceptibility loci, with P-values about 10-5. In the
      present study, an independent cohort was used for a replication study to evaluate
      the association of RAD54B and GREB1 with polycystic ovary syndrome (PCOS) in the
      Han Chinese population. Four single-nucleotide polymorphisms (SNP), rs2930961
      (RAD54B), rs12470971, rs11686574 and rs6740248 (GREB1), were genotyped in 1124
      PCOS patients and 1067 healthy controls from the Han Chinese population. Real
      time quantitative PCR by TaqMan-MGB probe assay was applied for genotyping. The
      allele and genotype frequencies of these four SNP were not significantly
      different in the replication cohort. However, the minor allele frequency of
      rs2930961 was significantly different in hyperandrogenism of PCOS. After meta
      analysis by combining the results of these two studies, there was a non
      significant trend for the association of rs2930961 (RAD54B) with PCOS. RAD54B and
      GREB1 gene polymorphisms may not be associated with PCOS in the Han Chinese
      population. Nevertheless, RAD54B may contribute to hyperandrogenism in PCOS
      patients.

PMID- 23876973
TI  - FSH receptor genotype does not predict metaphase-II oocyte output or
      fertilization rates in ICSI patients.
AB  - The objective of this study was to assess the role of the variant p.Asn680Ser in
      the FSH receptor gene (FSHR) in determining oocyte maturity. It also assessed the
      relationship between this FSHR variant with metaphase-II oocyte output rate (MOR)
      and the fertilization rate. This was a prospective observational study based at a
      tertiary referral centre for reproductive medicine. Women (n=212) undergoing
      their first cycle of ovarian stimulation for IVF with intracytoplasmic sperm
      injection (ICSI) were included in the study. Baseline pelvic ultrasound and blood
      tests were taken on day 2 or 3 of the cycle for assessment of baseline hormones
      and for DNA extraction. Genotypes for FSHR p.Asn680Ser was determined using
      TaqMan allelic discrimination assay. The outcome measures were the total dose of
      exogenous gonadotrophins used, antral follicle count (AFC), number of mature
      (metaphase-II) oocytes retrieved, MOR and fertilization rate. No statistically
      significant differences were found between the number of mature oocytes
      retrieved, MOR or fertilization rates among the patients with different
      p.Asn680Ser FSHR genotypes. No significant difference was noted in the clinical
      pregnancy rates per transfer. There is no evidence that the p.Asn680Ser FSHR
      genotype predicts oocyte maturity.

PMID- 23876974
TI  - (Male) infertility: what does it mean to men? New evidence from quantitative and
      qualitative studies.
AB  - Scientific knowledge of the emotional repercussions of infertility on men remains
      limited and has only recently become the focus of social science research.
      Firstly, the current developments in research on the psychosocial impact of
      infertility on men through a search of the literature over the last 10 years are
      outlined in this paper. In the second section, issues raised in pretreatment
      counselling for men and their partner who consider donor insemination are
      described as this treatment typically raises many emotional issues. The results
      of more recent studies with sophisticated methodological design show that the
      emotional impact of infertility may be nearly balanced, suggesting that men do
      suffer as well and that they have to be addressed in infertility counselling too.
      The emotional and clinical aspects of donor insemination support the hypothesis
      that the emotional repercussions of infertility affect both sexes. In general,
      male factor infertility seems to be more stigmatized than other infertility
      diagnoses. Forthcoming studies have to differentiate between the psychological
      impact of infertility on women and men and their respective abilities to
      communicate easily about this distress. More studies on infertile men in non
      Western societies need to be conducted in order to understand the cultural impact
      on infertility.

PMID- 23876975
TI  - [Infections caused by Clostridium difficile. Addendum].

PMID- 23876976
TI  - Single-nucleotide polymorphism array-based characterization of ring chromosome
      18.
AB  - OBJECTIVE: To study genotype-phenotype correlation of ring chromosome 18 [r(18)]
      in 9 patients with 46,XN karyotype. STUDY DESIGN: In 9 patients with a de novo
      46,XN,r(18) karyotype (7 females, 2 males), we performed high-resolution single
      nucleotide polymorphism array analysis (Illumina Human Omni1-QuadV1 array in 6
      patients, Affymetrix 6.0 array in 3 patients), investigation of parental origin,
      and genotype-phenotype correlation. RESULTS: No breakpoint was recurrent. Single
      metaphases with loss of the ring, double rings, or secondarily rearranged rings
      were found in some cases, but true mosaicism was present in none of these cases.
      In 3 patients, additional duplications in 18p (of 1.4 Mb, 2 Mb, and 5.8 Mb) were
      detected. In 1 patient, an additional deletion of 472 kb in Xp22.33, including
      the SHOX gene, was found. Parental origin of r(18) was maternal in 2 patients and
      paternal in 4 patients, and formation was most likely meiotic. Karyotype was
      normal in all investigated parents (n = 15). At birth, mean maternal age was 30
      years (n = 9) and mean paternal age was 34.4 years (n = 9). CONCLUSION: Genotype
      phenotype correlation revealed extensive clinical variability but no
      characteristic r(18) phenotype. Severity of clinical signs were generally
      correlated with the size of the deletion. Patients with large deletions in 18p
      and small deletions in 18q exhibited mainly symptoms related to 18p-, whereas
      those with large deletions in 18q and small deletions in 18p had symptoms of 18q
      .

PMID- 23876978
TI  - Targeted conformational search with map-restrained self-guided Langevin dynamics:
      application to flexible fitting into electron microscopic density maps.
AB  - We present a map-restrained self-guided Langevin dynamics (MapSGLD) simulation
      method for efficient targeted conformational search. The targeted conformational
      search represents simulations under restraints defined by experimental
      observations and/or by user specified structural requirements. Through map
      restraints, this method provides an efficient way to maintain substructures and
      to set structure targets during conformational searching. With an enhanced
      conformational searching ability of self-guided Langevin dynamics, this approach
      is suitable for simulating large-scale conformational changes, such as the
      formation of macromolecular assemblies and transitions between different
      conformational states. Using several examples, we illustrate the application of
      this method in flexible fitting of atomic structures into density maps derived
      from cryo-electron microscopy. 

PMID- 23876977
TI  - Travel-associated diseases, Indian Ocean Islands, 1997-2010.
AB  - Data collected by the GeoSentinel Surveillance Network for 1,415 ill travelers
      returning from Indian Ocean islands during 1997-2010 were analyzed. Malaria (from
      Comoros and Madagascar), acute nonparasitic diarrhea, and parasitoses were the
      most frequently diagnosed infectious diseases. An increase in arboviral diseases
      reflected the 2005 outbreak of chikungunya fever. 

PMID- 23876980
TI  - Modifying bone scaffold architecture in vivo with permanent magnets to facilitate
      fixation of magnetic scaffolds.
AB  - The fundamental elements of tissue regeneration are cells, biochemical signals
      and the three-dimensional microenvironment. In the described approach,
      biomineralized-collagen biomaterial functions as a scaffold and provides
      biochemical stimuli for tissue regeneration. In addition superparamagnetic
      nanoparticles were used to magnetize the biomaterials with direct nucleation on
      collagen fibres or impregnation techniques. Minimally invasive surgery was
      performed on 12 rabbits to implant cylindrical NdFeB magnets in close proximity
      to magnetic scaffolds within the lateral condyles of the distal femoral
      epiphyses. Under this static magnetic field we demonstrated, for the first time
      in vivo, that the ability to modify the scaffold architecture could influence
      tissue regeneration obtaining a well-ordered tissue. Moreover, the association
      between NdFeB magnet and magnetic scaffolds represents a potential technique to
      ensure scaffold fixation avoiding micromotion at the tissue/biomaterial
      interface. 

PMID- 23876979
TI  - Effect of chronic kidney disease on the healing of titanium implants.
AB  - Chronic kidney disease (CKD) has become a worldwide public health problem.
      However, its effect on osseointegration of dental implants is largely unknown.
      The aim of this study is to investigate whether CKD impairs the quality of the
      osseointegration of titanium implants. Uremia was induced by 5/6 nephrectomy in
      mice, and serum levels of BUN, FGF23, PTH and ALP were significantly increased.
      For in vitro tests, bone marrow mesenchymal stem cells (BMMSCs) were obtained and
      cultured on titanium discs. There was no significant difference in term of
      expression of osteogenic marker genes including Osx, Col-1, Ocn, and Opn, as
      quantified by qPCR. Moreover, Alizarin Red S staining showed comparable
      mineralized nodules formation. Histomorphometrical analysis of experimental
      implants inserted in the femurs of CKD mice revealed a trend of decreased BIC
      ratio at 2-week healing. The strength of bone-implant integration, as measured by
      a push-in method, was significantly lower for the CKD group at 2 weeks, although
      a comparable level was reached at 4 weeks. These results demonstrated that CKD
      only negatively affects the osseointegration of titanium implants at the early
      stage. 

PMID- 23876981
TI  - Sternal wall pressure comparable to leaning during CPR impacts intrathoracic
      pressure and haemodynamics in anaesthetized children during cardiac
      catheterization.
AB  - AIM: Force due to leaning during cardiopulmonary resuscitation (CPR) negatively
      affects haemodynamics and intrathoracic airway pressures (ITP) in animal models
      and adults, but has not been studied in children. We sought to characterize the
      effects of sternal force (SF) comparable to leaning force on haemodynamics and
      ITP in anaesthetized children. METHODS: Children (6 months to 8yrs) presenting
      for routine haemodynamic cardiac catheterization with anaesthesia and mechanical
      ventilation >6 months after cardiac transplant were studied. Haemodynamics and
      ITP were measured before and during incremental increases in SF of 10% and 20%
      body weight. RESULTS: 20 subjects (5.4+/-1.7yrs of age and 18.3+/-3.3kg) were
      studied. Mean right atrial pressure (6.5+/-2.6 at baseline vs. 7.7+/-2.6 at 10%
      SF vs. 8.6+/-2.7mmHg at 20% SF), mean pulmonary capillary wedge pressure (10.2+/
      2.9 at baseline vs. 11+/-3.3 at 10% SF vs. 11.8+/-3.4mmHg at 20% SF) and ITP
      (16.3+/-3.2 at baseline vs. 17.9+/-3.9 at 10% SF vs. 19.5+/-4cm H2O) all
      increased significantly with incremental SF (p<0.001 for all). Aortic systolic
      pressure (85+/-10mmHg at baseline vs. 83+/-10mmHg at 10% SF vs. 82+/-10mmHg at
      20% SF, p=0.014) and coronary perfusion pressure (42+/-7mmHg at baseline vs. 39+/
      7mmHg at 10% SF vs. 38+/-7mmHg at 20% SF, p<0.001) both decreased significantly
      with incremental SF. CONCLUSIONS: In asymptomatic, anaesthetized children after
      cardiac transplantation, sternal forces comparable to leaning previously reported
      to occur during CPR elevate ITP and right atrial pressure and decrease coronary
      perfusion pressure. These haemodynamic effects may be clinically important during
      CPR and warrant further study.

PMID- 23876982
TI  - Single-shock defibrillation success in adult cardiac arrest: a systematic review.
AB  - OBJECTIVE: Current resuscitation guidelines advise a single biphasic shock
      followed by chest compressions; however, it is unclear if this applies to all
      waveforms and energy levels. We conducted a systematic review of the literature
      to determine the comparative success rates for single-shock defibrillation across
      waveforms evaluated in out-of-hospital cardiac arrest patients. METHODS: EMBASE,
      MEDLINE, EBM Reviews, dissertation abstract databases, and clinicaltrials.gov
      were searched. Two investigators independently reviewed titles, abstracts and
      full texts in a hierarchical manner for study eligibility with a quadratic kappa
      score at each level. Two authors abstracted data independently and the quality of
      the articles was assessed using the five-point Jadad scale. Outcomes were
      termination of ventricular fibrillation (VF)/ventricular tachycardia (VT) at 5s
      post shock (TOF), return of organized rhythm (ROOR) and return of spontaneous
      circulation (ROSC). RESULTS: A total of 3281 potentially relevant citations were
      identified and, of these, eight papers were selected with Kappa values of 0.53
      for titles, 0.71 for abstracts, and 0.94 for articles. Quality scores varied from
      0 to 4/5. Biphasic first-shock success for all three outcomes of interest was
      similar regardless of energy levels, and uniformly superior to monophasic first
      shock success. Median time to first shock varied across trials based on level of
      randomization (first responders versus advanced life support tiered response) and
      may contribute to observed differences. Lack of variability across two waveforms
      precluded a meta-analytical approach. CONCLUSIONS: This systematic review
      suggests that evaluated biphasic waveforms have similar first-shock success as
      measured by the three outcomes of interest and all are superior to monophasic
      shocks.

PMID- 23876983
TI  - Bone propeller flap: a staged procedure.
AB  - The ideal reconstruction technique for complex defects of the lower limb consists
      of replacing tissue with similar tissue in an attempt to achieve a good
      functional result. A 23-year-old white male sustained a crush injury with a grade
      IIIB open ankle dislocation. After open reduction and fixation, the patient
      developed severe osteomyelitis at the tibiotalar joint requiring a staged and
      radical debridement with a substantial combined soft tissue and bony defect over
      the distal tibia, fibula, and talus area. The reconstructive approach consisted
      of a modified model of the propeller flap, implementing the spare part concept in
      a 2-stage procedure using a prefabricated and vascularized "double-barrel"
      fibular graft. At 17 months postoperatively, a plain radiograph showed bony union
      with complete and stable coverage of the soft tissue defect. The patient was
      fully weightbearing. In conclusion, there is evidence to suggest that the
      established concept of a soft tissue propeller flap can be implemented on bone.

PMID- 23876984
TI  - FMSTM scores and low-back loading during lifting--whole-body movement screening
      as an ergonomic tool?
AB  - BACKGROUND: Previous research suggests that a general whole-body movement screen
      could be used to identify personal movement attributes that promote potentially
      injurious low-back loading patterns at work. The purpose of this study was to
      examine the relationship between Functional Movement ScreenTM (FMS) composite
      scores and the low-back loading response to lifting. METHODS: Fifteen men who
      scored greater than 14 on the FMS (high-scorers) and 15 height- and weight
      matched low-scorers (FMS < 14) performed sagittally symmetric and asymmetric
      laboratory-based lifting tasks. A three-dimensional dynamic biomechanical model
      was used to calculate peak low-back loading levels, and the angle of the lumbar
      spine was captured at the instant when the peak compressive force was applied.
      RESULTS: Regardless of the lifting task performed, there were no differences in
      peak low-back compression (p >= 0.4157), anterior/posterior reaction shear (p >=
      0.5645), or medial/lateral reaction shear (p >= 0.2581) forces between the high-
      and low-scorers. At the instant when peak compressive forces were applied,
      differences in the lumbar spine angle between high- and low-scores were not
      statistically significant about the lateral bend (p >= 0.4215), axial twist (p >=
      0.2734), or flexion/extension (p >= 0.1354) axes, but there was a tendency for
      the lumbar spine to be more deviated in the low-scorers. CONCLUSIONS: Using the
      previously established injury prediction threshold value of 14, the composite FMS
      score was not related to the peak low-back loading magnitudes in lifting. Though
      not statistically significant, the tendency for the lumbar spines of low-scorers
      to be more deviated when the peak low-back compression force was imposed could be
      biomechanically meaningful because spinal load tolerance varies with posture.
      Future attempts to modify or reinterpret FMS scoring are warranted given that
      several previous studies have revealed links between composite FMS scores and
      musculoskeletal complaints.

PMID- 23876985
TI  - Is workplace satisfaction associated with self-reported quad bike loss of control
      events among farm workers in New Zealand?
AB  - This study investigated whether rural workers who have higher workplace
      satisfaction are less likely to report quad bike loss of control events (LCEs).
      Two independent samples of farmers completed a survey regarding LCEs and
      workplace satisfaction. In the first sample (n = 130) analysis revealed no
      relationship (p = 0.74) between workplace satisfaction and LCEs but lower rates
      of LCEs were reported by employees (IRR 0.52, 95%CI 0.31-0.86) compared to self
      employed participants. In the second sample (n = 112), workplace satisfaction was
      weakly related to LCEs (IRR 1.04, 95%CI 1.00, to 1.09) with participants who
      found their job more psychologically demanding more likely to have had an LCE
      (IRR 1.14, 95%CI 1.05-1.23). Exploring the role of psychological demands on
      safety behaviour with respect to quad bike use, may help to address this
      important safety issue. 

PMID- 23876986
TI  - Reprint of: environmental information for military planning.
AB  - A study was conducted to consider the implications of presenting Environmental
      Information (EI; information on current environmental features including weather,
      topography and visibility maps) for military planning to the growing audience of
      non-technical users; to provide guidance for ensuring usability and for
      development of a suitable EI interface, and to produce an EI concept interface
      mock-up to demonstrate initial design ideas. Knowledge was elicited from current
      EI users and providers regarding anticipated use of EI by non-specialists. This
      was combined with human factors and cognition expertise to produce guidance for
      data usability and development of an EI interface. A simple mock-up of an EI
      concept interface was developed. Recommendations for further development were
      made including application of the guidance derived, identification of a user test
      bed and development of business processes. 

PMID- 23876987
TI  - Synthesis and SAR of 4-aminocyclopentapyrrolidines as orally active N-type
      calcium channel inhibitors for inflammatory and neuropathic pain.
AB  - A novel series of N-type calcium channel inhibitors have been discovered.
      Optimization of potency and HT-ADME properties provides 4
      aminocyclopentapyrrolidines with analgesic efficacy after oral dosing. 

PMID- 23876988
TI  - Synthesis and binary QSAR study of antitubercular quinolylhydrazides.
AB  - In continuation with our previous work in anti-TB research area, in the present
      study we have demonstrated the structural diversity of quinolylhydrazides as
      potent anti-tuberculars. The compound library was synthesized by molecular
      hybridization approach and tested in vitro against Mycobacterium tuberculosis
      H37Rv strains. Among the designed conjugates, the most promising molecules were
      found to exhibit 100% Growth Inhibition (GI) at MIC <6.25 MUg/mL. Moreover,
      several analogs in the designed series were also turned out as excellent anti
      tuberculars. To probe the structural characteristics influencing on the SAR, the
      classification model was generated using a binary QSAR approach termed recursive
      partitioning (RP) analysis. The significant features outlined by the RP model act
      as a guide in order to design the 'lead' compound.

PMID- 23876989
TI  - Search for a novel SIRT1 activator: structural modification of SRT1720 and
      biological evaluation.
AB  - Syntheses and biological evaluation of novel SRT1720 derivatives are described in
      search for new candidates of SIRT1 activator. Several parts of the SRT1720
      structure, including piperazine moiety, quinoxaline ring on the amide group, and
      position of the amide function, were modified, and the assay results indicated
      that transfer of the ortho amide-substituent regarding to the imidazo[1,2
      b]thiazole core onto the meta position resulted in improvement of SIRT1
      activation ability. Modeling analyses of SRT1720 and the most potent derivative
      bound to model complex of SIRT1 with peptide substrate were also performed. 

PMID- 23876990
TI  - Family influence and psychiatric care: physical treatments in Devon mental
      hospitals, c. 1920 to the 1970s.
AB  - 'What is it that appears to make the mentally ill so vulnerable to therapeutic
      experimentation?'(1) One commentator wrote in the 1990s, regarding mental
      hospitals as repressive, coercive and custodial institutions where medical staff
      subjected patients to orgies of experimentation. A careful study of surviving
      documents of the Devon County Lunatic Asylum (DCLA), however, paints a different
      picture. Rather than medical staff, patients' relatives and the wider community
      exercised a considerable influence over a patient's hospital admission and
      discharge, rendering the therapeutic regime in the middle of the 20th century the
      result of intense negotiations between the hospital and third parties.

PMID- 23876991
TI  - Needs, concerns, strategies, and advice of daily home hemodialysis caregivers.
AB  - Improved patient outcomes have led to increased international interest in daily
      home hemodialysis as a kidney replacement therapy. Daily home hemodialysis often
      requires the assistance of a caregiver during and between treatments.
      Understanding the needs and concerns of caregivers of persons on daily home
      hemodialysis will inform the design of supportive interventions to improve
      caregiver retention and maintain their health and well-being. Using a descriptive
      qualitative design, the purpose of this study was to identify and describe the
      needs, concerns, strategies, and advice of family caregivers. Twenty-one
      caregivers were interviewed; five of these individuals were former caregivers of
      patients who had returned to outpatient hemodialysis. Data were collected via
      audio-recorded telephone interviews following a semistructured interview guide
      with five open-ended questions. A content analysis approach was used to code and
      analyze the data. Caregivers described needs, concerns, and strategies and
      offered advice in five predetermined major categories. Major findings included a
      need for respite services and a need for interventions to manage the emotional
      responses to caregiving. This study provides valuable information about relevant
      areas to consider when developing an intervention program for daily home
      hemodialysis caregivers. 

PMID- 23876993
TI  - Accounting for the phase, spatial frequency and orientation demands of the task
      improves metrics based on the visual Strehl ratio.
AB  - Advances in ophthalmic instrumentation have allowed high order aberrations to be
      measured in vivo. These measurements describe the distortions to a plane
      wavefront entering the eye, but not the effect they have on visual performance.
      One metric for predicting visual performance from a wavefront measurement uses
      the visual Strehl ratio, calculated in the optical transfer function (OTF) domain
      (VSOTF) (Thibos et al., 2004). We considered how well such a metric captures
      empirical measurements of the effects of defocus, coma and secondary astigmatism
      on letter identification and on reading. We show that predictions using the
      visual Strehl ratio can be significantly improved by weighting the OTF by the
      spatial frequency band that mediates letter identification and further improved
      by considering the orientation of phase and contrast changes imposed by the
      aberration. We additionally showed that these altered metrics compare well to a
      cross-correlation-based metric. We suggest a version of the visual Strehl ratio,
      VScombined, that incorporates primarily those phase disruptions and contrast
      changes that have been shown independently to affect object recognition
      processes. This metric compared well to VSOTF for letter identification and was
      the best predictor of reading performance, having a higher correlation with the
      data than either the VSOTF or cross-correlation-based metric. 

PMID- 23876994
TI  - Right ventricular mechanical dyssynchrony and asymmetric contraction in
      hypoplastic heart syndrome are associated with tricuspid regurgitation.
AB  - BACKGROUND: Right ventricular (RV) dysfunction and tricuspid regurgitation (TR)
      are associated with adverse outcome in hypoplastic left heart syndrome (HLHS) but
      remain poorly understood. The aim of this study was to assess RV longitudinal
      strain and mechanical dyssynchrony in HLHS in relation to TR. The hypothesis was
      that inhomogeneous RV contraction and mechanical dyssynchrony around the
      tricuspid valve apparatus may be associated with TR in some patients with HLHS.
      METHODS: Echocardiograms of children aged 0 to 2 years with HLHS at all stages of
      surgical palliation were retrospectively reviewed for anatomic subtype and
      severity of TR. RV peak strain and dyssynchrony were assessed by vector velocity
      imaging. RESULTS: Sixty echocardiograms of patients with a median age of 0.54
      years (interquartile range, 0.04-1.63 years) and a median weight 6.40 kg
      (interquartile range, 3.70-10.45 kg) demonstrated TR, which was absent or trivial
      in 25 (42%), mild in 20 (33%), moderate in five (8%), and severe in 10 (17%). The
      difference in peak longitudinal strain between the RV free wall and the septum or
      left-sided RV wall was significantly higher in patients with moderate or severe
      TR compared with no, trivial, or mild TR (2.93 +/- 6.03% vs 0.16 +/- 6.6%, P =
      .04). The difference in time to peak longitudinal strain between walls was
      significantly longer in moderate or severe TR compared with no, trivial, or mild
      TR (57.4 +/- 145.1 vs 15.8 +/- 75.9 msec, P = .04). There was a significant
      difference in anatomic subtype between patients with the most difference in peak
      strain compared with those with the least. CONCLUSIONS: RV mechanical
      dyssynchrony and inhomogeneous contraction are worse in patients with clinically
      important TR and HLHS.

PMID- 23876995
TI  - Calcification of the mitral valve and annulus: systematic evaluation of effects
      on valve anatomy and function.
AB  - BACKGROUND: Mitral annular calcification (MAC) is common in chronic kidney
      disease. It is associated with cardiovascular events and can cause valvular
      dysfunction, but it has not been systematically characterized. The aim of this
      prospective study was to assess the prevalence and distribution of MAC, its
      effects on leaflet motion, and its association with mitral stenosis and mitral
      regurgitation (MR) in a hemodialysis population. METHODS: Echocardiograms were
      obtained in 75 consecutive hemodialysis outpatients. MAC extent and distribution
      were graded semiquantitatively using two-dimensional and three-dimensional
      echocardiography. Associations with the presence and severity of mitral stenosis
      and MR were explored. RESULTS: The mean age was 60 +/- 14 years; 60% were men,
      and 87% were African American. MAC was present in 64% (moderate to severe in
      48%). Calcium extended more than halfway onto the leaflet in 37% and beyond the
      annulus in 40%. Leaflet motion was restricted in 37%. Mitral stenosis was present
      in 28%, and the extent of calcification was associated with mean mitral valve
      gradient (P < .0001). MR was prevalent (present in 81%) but was severe in none.
      The severity of MAC was greater in patients with moderate MR than in those with
      no or mild MR (P = .04). Three-dimensional analysis suggested an uneven
      distribution of annular calcium; the middle and lateral anterior segments were
      less often calcified than the anterior-medial or posterior segments.
      Calcification in any annular segment was highly associated with restricted motion
      of the attached leaflet segment. CONCLUSIONS: MAC is common and often extensive
      in hemodialysis patients. Calcium may be unevenly distributed among the annular
      segments. When present, annular calcification reduces the angle of leaflet
      opening and can cause valvular dysfunction.

PMID- 23876996
TI  - Velocity vector imaging in the measurement of left ventricular myocardial
      mechanics on cardiac magnetic resonance imaging: correlations with
      echocardiographically derived strain values.
AB  - BACKGROUND: Regional and global function can be measured by echocardiography
      using speckle-tracking, a technique that has previously been validated against
      crystal sonomicrometry. However, the application of Velocity Vector Imaging (VVI)
      to images obtained from cardiac magnetic resonance (CMR) imaging has never been
      validated against those values derived from VVI applied to two-dimensional
      echocardiographic images in the same patient group. The aim of this study was to
      validate for the first time the application of VVI to retrospectively acquired
      CMR data sets for the assessment of left ventricular strain and rotation, using
      echocardiographic strain assessment by VVI as the reference technique. METHODS:
      Cine steady-state free precession CMR data sets and two-dimensional
      echocardiographic images obtained on the same day in 36 adult patients with
      hypertrophic cardiomyopathy were analyzed retrospectively using VVI to quantify
      global longitudinal and circumferential strain and rotation parameters. RESULTS:
      The absolute differences in longitudinal strain between the two imaging
      modalities were -1.1 +/- 3.3% (endocardial) and -2.2 +/- 3.6% (full thickness).
      The absolute differences in circumferential strain were -4.7 +/- 5.3%
      (endocardial) and -3.4 +/- 3.8% (full thickness). CMR consistently resulted in
      higher strain values than echocardiography. The absolute differences in twist
      were -0.2 +/- 5.6% (endocardial) and 0.1 +/- 5.8% (full thickness). CONCLUSIONS:
      The application of VVI to CMR data sets allows a feasible and reproducible method
      for strain analysis in HCM, demonstrating excellent agreement with two
      dimensional echocardiography-derived values. Given the superior image quality
      obtained with CMR in a significant proportion of patients, this technique
      provides a method for strain assessment without the need for dedicated CMR
      acquisition and analytic techniques.

PMID- 23876997
TI  - Assessing co-regulation of directly linked genes in biological networks using
      microarray time series analysis.
AB  - Differential expression of genes detected with the analysis of high throughput
      genomic experiments is a commonly used intermediate step for the identification
      of signaling pathways involved in the response to different biological
      conditions. The impact analysis was the first approach for the analysis of
      signaling pathways involved in a certain biological process that was able to take
      into account not only the magnitude of the expression change of the genes but
      also the topology of signaling pathways including the type of each interactions
      between the genes. In the impact analysis, signaling pathways are represented as
      weighted directed graphs with genes as nodes and the interactions between genes
      as edges. Edges weights are represented by a beta factor, the regulatory
      efficiency, which is assumed to be equal to 1 in inductive interactions between
      genes and equal to -1 in repressive interactions. This study presents a
      similarity analysis between gene expression time series aimed to find
      correspondences with the regulatory efficiency, i.e. the beta factor as found in
      a widely used pathway database. Here, we focused on correlations among genes
      directly connected in signaling pathways, assuming that the expression variations
      of upstream genes impact immediately downstream genes in a short time interval
      and without significant influences by the interactions with other genes. Time
      series were processed using three different similarity metrics. The first metric
      is based on the bit string matching; the second one is a specific application of
      the Dynamic Time Warping to detect similarities even in presence of stretching
      and delays; the third one is a quantitative comparative analysis resulting by an
      evaluation of frequency domain representation of time series: the similarity
      metric is the correlation between dominant spectral components. These three
      approaches are tested on real data and pathways, and a comparison is performed
      using Information Retrieval benchmark tools, indicating the frequency approach as
      the best similarity metric among the three, for its ability to detect the
      correlation based on the correspondence of the most significant frequency
      components. 

PMID- 23876998
TI  - The integration of high-throughput testing of blood donors for cardiovascular
      disease risk assessment and prevention.
AB  - BACKGROUND AND OBJECTIVES: Some blood centers provide health screening as a
      public health measure and to encourage donation. The goal of the current study
      was to provide cardiovascular disease (CVD) screening to donors using high
      throughput testing and web-based communications. MATERIALS AND METHODS: CVD risk
      screening was offered to donors at selected mobile drives in a large metropolitan
      area. Risk factors were determined by donor questionnaire, laboratory testing
      (total cholesterol, HDL levels and hemoglobin A1c), and blood pressure
      measurement. Results were reported to participants via mail and website. A 60-day
      follow up web-based survey was sent to participants via email to assess the
      impact of the program on donor's behavior. RESULTS: 9435 donors, 17-75 years old
      participated with the following risk factors: 61.3% BMIs>25, 28.8% high total
      cholesterol, and 31.4% lower than recommended HDL levels. 25.3% of donors that
      responded to the follow up survey went to see their health care provider based on
      screening results and 9% of these received new or modified treatment. CONCLUSION:
      In our sample, blood donors are healthier than the general population, but many
      still have CVD risk factors, particularly obesity. CVD screening can be
      successfully used to make donors aware of this important health information and
      some donors act on this information.

PMID- 23876999
TI  - Cloning and molecular characterization of complement component 1 inhibitor
      (C1INH) and complement component 8beta (C8beta) in Nile tilapia (Oreochromis
      niloticus).
AB  - Nile tilapia (Oreochromis niloticus), one of the most important groups of food
      fishes in the world, has frequently suffered from serious challenge from
      pathogens in recent years. Immune responses of Nile tilapia should be understood
      to protect the aquaculture industry of this fish. The complement system has an
      important function in recognizing bacteria, opsonizing these pathogens by
      phagocytes, or killing them by direct lysis. In this study, two Nile tilapia
      complement component genes, complement component 1 inhibitor (C1INH) and
      complement component 8beta subunit (C8beta), were cloned and their expression
      characteristics were analyzed. C1INH cDNA was found containing a 1791 bp open
      reading frame (ORF) encoding a putative protein with 597 amino acids, a 101 bp 5'
      untranslated region (UTR) and a 236 bp 3'-UTR. The predicted protein structure
      for this gene consisted of two Ig-like domains and glycosyl hydrolase family-9
      active site signature 2. The C8beta cDNA consisted of a 1761 bp ORF encoding 587
      amino acids, a 15 bp 5'-UTR and a 170 bp 3'-UTR. The predicted protein of C8beta
      contained three motifs, thrombospondin type-1 repeat, membrane attack
      complex/perforin domain, and LDL-receptor class A. Expression analysis revealed
      that these two complement genes were highly expressed in the liver, however, were
      weakly expressed in the gill, heart, brain, kidney, intestine, spleen and dorsal
      muscle tissues. The present study provided insights into the complement system
      and immune functions of Nile tilapia.

PMID- 23877000
TI  - Cloning and expression analysis of a HSP70 gene from Korean rockfish (Sebastes
      schlegeli).
AB  - The gene encoding HSP70 was isolated from Korean rockfish Sebastes schlegeli by
      homologous cloning and rapid amplification of cDNA ends (RACE). The full-length
      of HSP70 cDNA was composed of 2259 bp and encoded a polypeptide of 639 amino
      acids. BLAST analysis showed that HSP70 of S. schlegeli shared high identities
      with those of the Lates calcarifer, Oreochromis niloticus, Seriola quinqueradiata
      HSP70s (88-89%). Our current study also revealed that HSP70 of Korean rockfish
      was expressed in many tissues by RT-PCR under unstressed condition. Quantitative
      real-time PCR showed that the expression patterns of Korean rockfish HSP70 were
      developmental stage-dependency. The expression of HSP70 was measured by
      quantitative real-time PCR after different oxygen treatments. The results showed
      that expression of HSP70 increased significantly after exposure to hypoxia for 30
      min in gill and ovary, and then decreased for 60 min, and the level in spleen and
      liver gradually increased and reached the highest at 60 min. In addition, in
      gill, spleen and liver, the HSP70 mRNA level reached the maximum in hypoxia group
      after one hour different oxygen concentration stress. Increased amounts of serum
      thyroxine (T4), and triiodothyronine (T3) were also found during 30 min hypoxia
      treatment and 60 min normoxia group in our study. All of the results provide
      information to further study the mechanism of physiology and immune function
      under stress conditions of ovoviviparous teleosts. 

PMID- 23877001
TI  - Deciduous and evergreen trees differ in juvenile biomass allometries because of
      differences in allocation to root storage.
AB  - BACKGROUND AND AIMS: Biomass partitioning for resource conservation might affect
      plant allometry, accounting for a substantial amount of unexplained variation in
      existing plant allometry models. One means of resource conservation is through
      direct allocation to storage in particular organs. In this study, storage
      allocation and biomass allometry of deciduous and evergreen tree species from
      seasonal environments were considered. It was expected that deciduous species
      would have greater allocation to storage in roots to support leaf regrowth in
      subsequent growing seasons, and consequently have lower scaling exponents for
      leaf to root and stem to root partitioning, than evergreen species. It was
      further expected that changes to root carbohydrate storage and biomass allometry
      under different soil nutrient supply conditions would be greater for deciduous
      species than for evergreen species. METHODS: Root carbohydrate storage and organ
      biomass allometries were compared for juveniles of 20 savanna tree species of
      different leaf habit (nine evergreen, 11 deciduous) grown in two nutrient
      treatments for periods of 5 and 20 weeks (total dry mass of individual plants
      ranged from 0.003 to 258.724 g). KEY RESULTS: Deciduous species had greater root
      non-structural carbohydrate than evergreen species, and lower scaling exponents
      for leaf to root and stem to root partitioning than evergreen species. Across
      species, leaf to stem scaling was positively related, and stem to root scaling
      was negatively related to root carbohydrate concentration. Under lower nutrient
      supply, trees displayed increased partitioning to non-structural carbohydrate,
      and to roots and leaves over stems with increasing plant size, but this change
      did not differ between leaf habits. CONCLUSIONS: Substantial unexplained
      variation in biomass allometry of woody species may be related to selection for
      resource conservation against environmental stresses, such as resource
      seasonality. Further differences in plant allometry could arise due to selection
      for different types of biomass allocation in response to different environmental
      stressors (e.g. fire vs. herbivory).

PMID- 23877003
TI  - Oxygen deficient centers in silica: optical properties within many-body
      perturbation theory.
AB  - The electronic and optical properties of neutral oxygen vacancies, also called
      oxygen deficient centers (ODC(I)s), have been investigated in pure and germanium
      doped silica (both amorphous and alpha-quartz) through first-principles
      calculations. By means of density functional theory and many-body perturbation
      theory (GW approximation and the solution of the Bethe-Salpeter equation), we
      obtain the atomic and electronic structures as well as the optical absorption
      spectra of pure and Ge-doped silica in the presence of ODCs (SiODC(I)s and
      GeODC(I)s); our study allows us to interpret and explain the very nature of the
      optical features in experimental absorption spectra. The theoretical optical
      absorption signatures of these defects show excellent agreement with experiments
      for the SiODC(I)s, i.e. two absorption bands arise around 7.6 eV due to
      transitions between the defect levels. Our theoretical results also explain the
      experimental difficulty in measuring the GeODC(I) absorption band in Ge-doped
      silica, which was in fact tentatively assigned to a broad and very weak
      absorption signature, located between 7.5 and 8.5 eV. The influence of Ge-doping
      induced disorder on the nature of the defect-related optical transitions is
      discussed. We find that even if the atomic and electronic structures of SiODC(I)
      and GeODC(I) defects are relatively similar, the slight network distortion
      induced by the presence of the Ge atom, together with the increase in the Ge-Si
      bond asymmetry, completely changes the nature of the optical absorption edge. 

PMID- 23877004
TI  - Understanding on-road practices of electric bike riders: an observational study
      in a developed city of China.
AB  - Although millions of electric bikes (E-bikes) operate in China and many
      associated deaths and injuries have been reported, E-bikers' on-road practices
      are poorly characterized and few direct observational studies have been
      performed. This study aims to describe riding behaviors among E-bikers and to
      investigate factors influencing these practices to inform injury prevention. In
      March 2012, a cross-sectional observational study was conducted at 14 randomly
      selected intersections in Suzhou during a 7-day period. A pro-forma observation
      checklist was used to collect data on road riding practice. Adjusted Odds Ratios
      (OR) and 95% Confidence Intervals (CI) to assess the likelihood of specific
      riding practices among E-bikers were evaluated using mixed-effects logistic
      regression. Among 18,150 E-bikers observed, 37.6% rode E-bikes with cycling
      pedals, 86.0% of E-bikes were registered, 26.6% did not comply with the road
      rules, and 41.1% wore at least one safety item. The overall prevalence of
      carrying passengers, riding in a motor vehicle lane, running red lights, riding
      in opposite directions (i.e., facing oncoming traffic), mobile phone use, and
      helmet use were 12.4% (95%CI: 11.9-12.9%), 1.9% (95%CI: 1.7-2.1%), 4.8% (95%CI:
      4.5-5.1%), 3.4% (95%CI: 3.1-3.7%), 0.4% (95%CI: 0.3-0.5%), and 9.0% (95%CI: 8.5
      9.4%), respectively. Male E-bikers was associated with increased helmet use and
      riding in motor vehicle lanes, whereas riding a registered E-bike was associated
      with reduced likelihood of carrying passengers. This study demonstrates common
      road rule violations and low helmet use among E-bikers and supports the urgent
      need to develop additional regulations and behavioral interventions to improve
      safety practice among E-bikers in China. 

PMID- 23877005
TI  - Whole genome sequencing of an unusual serotype of Shiga toxin-producing
      Escherichia coli.
AB  - Shiga toxin-producing Escherichia coli serotype O117:K1:H7 is a cause of
      persistent diarrhea in travelers to tropical locations. Whole genome sequencing
      identified genetic mechanisms involved in the pathoadaptive phenotype. Sequencing
      also identified toxin and putative adherence genes flanked by sequences
      indicating horizontal gene transfer from Shigella dysenteriae and Salmonella
      spp., respectively. 

PMID- 23877006
TI  - Pseudo-hypertriglyceridaemia or hyperglycerolemia?
AB  - Hyperglycerolemia is a very rare genetic disorder caused by glycerol kinase
      deficiency. Although usually is presented unexpectedly in routine checks, there
      are severe forms, especially in children. In general, glycerol and glycerol
      kinase activity analyses are not included in routine laboratory determination.
      Glycerol presents positive interferences with some biochemical analytic
      techniques, e.g. in serum triglycerides and plasma ethylene glycol levels assays.
      Here, we report a Spanish patient with a pseudo-hypertriglyceridaemia, a falsely
      elevated triglycerides concentration that was not corrected with lipid-lowering
      therapy for 3 years. 

PMID- 23877007
TI  - Two-dimensional analysis of glycated hemoglobin heterogeneity in pediatric type 1
      diabetes patients.
AB  - Interindividual and ethnic variation in glycated hemoglobin levels, unrelated to
      blood glucose variation, complicates the clinical use of glycated hemoglobin
      assays for the diagnosis and management of diabetes. Assessing the types and
      amounts of glycated hemoglobins present in erythrocytes could provide insight
      into the mechanism. Blood samples and self-monitored mean blood glucose (MBG)
      levels were obtained from 85 pediatric type 1 diabetes patients. Glycated
      hemoglobin levels were measured using three primary assays (boronate-affinity
      chromatography, capillary isoelectric focusing (CIEF), and standardized DCA2000+
      immunoassay) and a two-dimensional (2D) analytical system consisting of boronate
      affinity chromatography followed by CIEF. The 2D system separated hemoglobin into
      five subfractions, four of which contained glycated hemoglobins. Glycated
      hemoglobin measurements were compared in patients with low, moderate, or high
      hemoglobin glycation index (HGI), a measure of glycated hemoglobin controlled for
      blood glucose variation. MBG was not significantly different between HGI groups.
      Glycated hemoglobin levels measured by all three primary assays and in all four
      glycated 2D subfractions were significantly different between HGI groups and
      highest in high HGI patients. These results show that interindividual variation
      in glycated hemoglobin levels was evident in diabetes patients with similar blood
      glucose levels regardless of which glycated hemoglobins were measured. 

PMID- 23877008
TI  - Continuous enzyme-coupled assay for microbial transglutaminase activity.
AB  - Transglutaminases (protein-glutamine:amine gamma-glutamyltransferase, EC
      2.3.2.13) are a family of calcium-dependent enzymes that catalyze an acyl
      transfer between glutamine residues and a wide variety of primary amines. When a
      lysine residue acts as the acyl-acceptor substrate, a gamma-glutamyl-epsilon
      lysine isopeptide bond is formed. This isopeptide bond formation represents
      protein cross-linking, which is critical to several biological processes.
      Microbial transglutaminase (mTG) is a bacterial variant of the transglutaminase
      family, distinct by virtue of its calcium-independent catalysis of the
      isopeptidic bond formation. Furthermore, mTG's promiscuity in acyl-acceptor
      substrate preference highlights its biocatalytic potential. The acyl-donor
      substrate, however, is limited in its scope; the amino acid sequences flanking
      glutamine residues dramatically affect substrate specificity and activity. Here,
      we have developed and optimized a modified glutamate dehydrogenase assay with the
      intention of analyzing potential high-affinity peptides. This direct continuous
      assay presents significant advantages over the commonly used hydroxamate assay,
      including generality, sensitivity, and ease of manipulation. Furthermore, we
      identified 7M48 (WALQRPH), a high-affinity peptide that shows greater affinity
      with mTG (K(M)=3 mM) than the commonly used Cbz-Gln-Gly (K(M)=58 mM), attesting
      to its potential for application in biocatalysis and bioconjugation.

PMID- 23877009
TI  - Sorafenib/regorafenib and phosphatidyl inositol 3 kinase/thymoma viral proto
      oncogene inhibition interact to kill tumor cells.
AB  - The present studies were undertaken to determine whether the multikinase
      inhibitors sorafenib/regorafenib cooperated with clinically relevant ,
      phosphatidyl inositol 3 kinase (PI3K)-thymoma viral proto-oncogene (AKT)
      inhibitors to kill tumor cells. In liver, colorectal, lung, breast, kidney, and
      brain cancer cells, at clinically achievable doses, sorafenib/regorafenib and the
      PI3K inhibitor acetic acid (1S,4E,10R,11R,13S,14R)-[4-diallylaminomethylene-6
      hydroxy-1-methoxymethyl-10,13-dimethyl-3,7,17-trioxo
      1,3,4,7,10,11,12,13,14,15,16,17-dodecahydro-2-oxa-cyclopenta[a]phenanthren-11-yl
      ester (PX-866) cooperated in a greater than additive fashion to kill tumor cells.
      Cells lacking phosphatase and tensin homolog were as sensitive to the drug
      combination as cells expressing the protein. Similar data were obtained using the
      AKT inhibitors perifosine and 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-1,2,4
      triazolo[3,4-f] [1,6]naphthyridin-3(2H)-one hydrochloride (MK2206). PX-866
      treatment abolished AKT/glycogen synthase kinase 3 (GSK3) phosphorylation, and
      cell killing correlated with reduced activity of AKT and mammalian target of
      rapamycin (mTOR). Expression of activated AKT and to a lesser extent activated
      mTOR reduced drug combination lethality. Expression of B-cell lymphoma-extra
      large or dominant negative caspase 9, but not cellular FLICE (FADD-like IL-1b
      converting enzyme)-inhibitory protein short, protected cells from the drug
      combination. Treatment of cells with PX-866 increased protein levels of p62,
      lysosome-associated membrane protein 2 (LAMP2), and microtubule-associated
      protein light chain (LC) 3 and LC3II that correlated with a large increase in LC3
      green fluorescent protein (GFP) vesicle numbers. Exposure of PX-866 treated cells
      to sorafenib reduced p62 and LAMP2 levels, decreased the ratio of LC3 to LC3II,
      and reduced LC3-GFP vesicle levels. Knockdown of Beclin1 or autophagy-related 5
      suppressed drug toxicity by ~40%. In vivo, sorafenib and PX-866 or regorafenib
      and MK2206 cooperated to suppress the growth of established HuH7 and HCT116
      tumors, respectively. Collectively our data demonstrate that the combination of
      sorafenib family kinase inhibitors with inhibitors of the PI3K/AKT pathway kills
      tumor cells in vitro and in vivo. 

PMID- 23877010
TI  - Multiple binding sites for small-molecule antagonists at the CC chemokine
      receptor 2.
AB  - The chemokine receptor CCR2 is a G protein-coupled receptor that is activated
      primarily by the endogenous CC chemokine ligand 2 (CCL2). Many different small
      molecule antagonists have been developed to inhibit this receptor, as it is
      involved in a variety of diseases characterized by chronic inflammation.
      Unfortunately, all these antagonists lack clinical efficacy, and therefore a
      better understanding of their mechanism of action is warranted. In this study, we
      examined the pharmacological properties of small-molecule CCR2 antagonists in
      radioligand binding and functional assays. Six structurally different antagonists
      were selected for this study, all of which displaced the endogenous agonist
      (125)I-CCL2 from CCR2 with nanomolar affinity. Two of these antagonists, INCB3344
      [N-(2-(((3S,4S)-1-((1r,4S)-4-(benzo[d][1,3]dioxol-5-yl)-4-hydroxycyclohexyl)-4
      ethoxypyrrolidin-3-yl)amino)-2-oxoethyl)-3-(trifluoromethyl)benzamide] and CCR2
      RA, were radiolabeled to study the binding site in greater detail. We discovered
      that [(3)H]INCB3344 and [(3)H]CCR2-RA bind to distinct binding sites at CCR2, the
      latter being the first allosteric radioligand for CCR2. Besides the binding
      properties of the antagonists, we examined CCR2 inhibition in multiple functional
      assays, including a novel label-free whole-cell assay. INCB3344 competitively
      inhibited CCL2-induced G protein activation, whereas CCR2-RA showed a
      noncompetitive or allosteric mode of inhibition. These findings demonstrated that
      the CCR2 antagonists examined in this study can be classified into two groups
      with different binding sites and thereby different modes of inhibition. We have
      provided further insights in CCR2 antagonism, and these insights are important
      for the development of novel CCR2 inhibitors. 

PMID- 23877011
TI  - Teamwork in microtubule motors.
AB  - Diverse cellular processes are driven by the collective force from multiple motor
      proteins. Disease-causing mutations cause aberrant function of motors, but the
      impact is observed at a cellular level and beyond, therefore necessitating an
      understanding of cell mechanics at the level of motor molecules. One way to do
      this is by measuring the force generated by ensembles of motors in vivo at single
      motor resolution. This has been possible for microtubule motor teams that
      transport intracellular organelles, revealing unexpected differences between
      collective and single-molecule function. Here we review how the biophysical
      properties of single motors, and differences therein, may translate into
      collective motor function during organelle transport and perhaps in other
      processes outside transport. 

PMID- 23877012
TI  - Perifosine, an AKT inhibitor, modulates ovarian cancer cell line sensitivity to
      cisplatin-induced growth arrest.
AB  - OBJECTIVES: AKT, a key regulator of diverse tumor signaling, is associated with
      progression of many cancers. Here, we investigated 1) the influence of AKT on
      survival from ovarian cancer (OVCA), 2) the activity of the AKT inhibitor
      perifosine +/- cisplatin, and 3) the molecular determinants of perifosine
      response. Phospho-AKT expression values and Affymetrix U133a expression data were
      downloaded from The Cancer Genome Atlas. METHODS: Pearson correlation was used to
      determine associations between overall survival from OVCA and therapy response.
      Genes and represented signaling pathways associated with perifosine-response were
      explored in OVCA cells (n=10) and the NCI60 cancer cell panel. Pathway
      expressions, modeled by PCA, were evaluated for influences on survival using
      publically available clinico-genomic datasets. RESULTS: Phospho-AKT (serine473)
      expression correlated with survival from OVCA (P<0.05) and platinum-response
      (P=0.004). In vitro, perifosine showed anti-proliferative effects against OVCA
      cells and potentiated cisplatin-induced growth arrest. Perifosine-response was
      associated with the expression (FDR<0.05) of 7 signaling pathways in OVCA cells
      and 64 signaling pathways in the NCI60 cell panel. Three pathways were found in
      common: 1) Cytoskeleton remodeling/cytoskeleton remodeling (cyto), 2) cell
      adhesion/chemokines and adhesion (chemokines), and 3) cytoskeleton remodeling/TGF
      WNT (TGF-WNT). The TGF-WNT was associated with survival from OVCA (P=0.0055).
      CONCLUSIONS: AKT signaling is an important determinant of OVCA response to
      chemotherapy and overall patient survival. Our data provide insight into the
      molecular basis to perifosine activity and identifies pathways associated with
      perifosine sensitivity and patient clinical outcome.

PMID- 23877013
TI  - The time interval from surgery to start of chemotherapy significantly impacts
      prognosis in patients with advanced serous ovarian carcinoma - analysis of
      patient data in the prospective OVCAD study.
AB  - OBJECTIVE: Cytoreductive surgery and platinum-based systemic therapy constitute
      the standard treatment of patients with advanced ovarian cancer. The aim of the
      present study was to evaluate whether the time interval from surgery to start of
      chemotherapy has an impact on clinical outcome. METHODS: Data of 191 patients
      with advanced serous (FIGO III-IV) ovarian cancer from the prospective
      multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients
      underwent primary surgery followed by platinum-based chemotherapy. RESULTS: The
      25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy
      were 22, 28, and 38 days, respectively (range, 4-158 days). Preoperative
      performance status (P<0.001), extent of surgery (P<0.001), and perioperative
      complications (P<0.001) correlated with intervals from surgery to initiation of
      chemotherapy. Timing of cytotoxic treatment [<= 28 days versus >28 days; hazard
      ratio (HR) 1.73 (95% confidence interval 1.08-2.78), P=0.022], residual disease
      [HR 2.95 (95% confidence interval 1.87-4.67), P<0.001], and FIGO stage [HR 2.26
      (95% confidence interval 1.41-3.64), P=0.001] were significant prognostic factors
      for overall survival in multivariate analysis. While the interval from surgery to
      start of chemotherapy did not possess prognostic significance in patients without
      postoperative residual disease (n=121), it significantly correlated with overall
      survival in patients with postoperative residual disease [n=70, HR 2.24 (95%
      confidence interval 1.08-4.66), P=0.031]. CONCLUSION: Our findings suggest that
      delayed initiation of chemotherapy might compromise overall survival in patients
      with advanced serous ovarian cancer, especially when suboptimally debulked.

PMID- 23877014
TI  - Radiation therapy for pelvic lymph node metastasis from uterine cervical cancer.
AB  - OBJECTIVES: This study aimed to evaluate the efficacy of radiation therapy for
      pelvic lymph node metastasis from uterine cervical cancer and identify an optimal
      radiation regimen. METHODS: A total of 111 metastatic pelvic lymph nodes, ranging
      from 11 to 56 mm (median, 25 mm) on CT/MRI, in 62 patients with uterine cervical
      cancer were treated initially with curative radiation therapy, with 46 patients
      receiving concurrent chemotherapy. Total radiation doses ranged from 45 to 61.2
      Gy (median, 50.4 Gy) in 1.8-2 Gy (median, 1.8 Gy) fractions. RESULTS: At a median
      follow-up of 33 months, 46 of the 62 patients survived. Only 2 irradiated lymph
      nodes, 24 and 28 mm in diameter, in 1 patient progressed after irradiation alone
      with 50.4 Gy in 1.8 Gy fractions. All 33 metastatic lymph nodes >= 30 mm in
      diameter were controlled by irradiation at a median dose of 55.8 Gy. The 3-year
      lymph node-progression free rates were 98.2% in all 62 patients and 98.0% in all
      111 metastatic lymph nodes. Except for transient hematologic reactions, 2
      patients developed grade >= 3 therapy-related toxicities, 1 with an ulcer and the
      other with perforation of the sigmoid colon. In addition, 2 patients experienced
      ileus after irradiation. CONCLUSIONS: Radiation therapy effectively controlled
      pelvic lymph node metastases in patients with uterine cervical cancer, with most
      nodes <24 mm in diameter controlled by total doses of 50.4 Gy in 1.8 Gy fractions
      and larger nodes controlled by 55.8 Gy, particularly with concurrent
      chemotherapy. Higher doses to metastatic lymph nodes may increase intestinal
      toxicities.

PMID- 23877015
TI  - Clinical outcome and prognostic markers for patients with gynecologic
      malignancies in phase 1 clinical trials: a single institution experience from
      1999 to 2010.
AB  - OBJECTIVES: There is a scarcity of outcome data regarding phase 1 trials for
      patients with gynecologic malignancy. The objective of this study was to assess
      toxicity, clinical benefit and prognosticators in gynecologic oncology patients
      participating in phase 1 trials. METHODS: All phase 1 oncology trials conducted
      at Albert Einstein Cancer Center from 1999 to 2010 were reviewed and extracted
      for relevant demographic and clinical data concerning patients with gynecologic
      malignancy. Cox-proportional and logistic regression modeling were used for
      multivariate analysis. RESULTS: 120 distinct patients with gynecologic malignancy
      participated in 41 trials, constituting 30.6% of all phase 1 patients enrolled in
      the same time period. The median age is 59 years. Out of the 184 patients
      enrolled, 160 individual responses were evaluable. Seventeen DLT events (9.2%)
      occurred, including 1 (0.5%) treatment-related mortality. There were 27.2%>=
      grade 3 hematologic and 24.4% non-hematologic toxicity. Eighty patients had
      stable disease (SD, 50%), including 21.9% with SD >= 4 months, 11 (6.3%) with
      partial response (PR), and 3 (1.9%) achieving complete response (CR). The
      clinical benefit rate (CBR=SD+CR+PR) was 58.1%. Albumin (Alb)<= 3.5 g/dL and
      abnormal ANC were independent negative prognosticators of survival. We also found
      a continuous correlation between changes in Albumin (p=0.02) and LDH (p=0.02) and
      odds of achieving CBR>=4month. CONCLUSIONS: Our clinical outcome and safety data
      suggested that phase 1 trials may be a reasonable option for patients with
      advanced and recurrent gynecologic cancer. The potential prognosticators
      identified should be further validated in larger trials.

PMID- 23877016
TI  - Pioglitazone does not affect the risk of ovarian cancer: analysis of a nationwide
      reimbursement database in Taiwan.
AB  - BACKGROUND: The association between pioglitazone and ovarian cancer has not been
      studied. METHODS: The reimbursement databases of all Taiwanese patients with a
      diagnosis of diabetes and under oral anti-diabetic agents or insulin from 1996 to
      2009 were retrieved from the National Health Insurance. An entry date was set at
      1 January 2006 and a total of 546,632 female patients with type 2 diabetes were
      followed up for ovarian cancer incidence until the end of 2009. Incidences for
      ever-users, never-users and subgroups of pioglitazone exposure [using cutoffs of
      the Kaiser Permanente Northern California study and tertile cutoffs derived from
      the databases] were calculated and the hazard ratios were estimated by Cox
      regression in unadjusted, age-adjusted and fully adjusted models. RESULTS: There
      were 30,783 ever-users and 515,849 never-users, with respective numbers of
      incident ovarian cancer of 49 (0.16%) and 946 (0.18%), and respective incidence
      of 43.08 and 51.47 per 100,000 person-years. The overall hazard ratios (95%
      confidence intervals) in unadjusted, age-adjusted and fully adjusted models were
      0.822 (0.616-1.095), 0.823 (0.617-1.097) and 0.968 (0.718-1.305), respectively.
      In the dose-response analyses, none of the categories showed a significant hazard
      ratio, and all P-trends were >0.05 without statistical significance. CONCLUSIONS:
      This study does not support a positive or negative association between
      pioglitazone use and ovarian cancer in female patients with type 2 diabetes.

PMID- 23877018
TI  - Antitumor activity of (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino)
      thiazolidin-4-one, a novel microtubule-depolymerizing agent, in U87MG human
      glioblastoma cells and corresponding mouse xenograft model.
AB  - Glioblastoma is the most lethal brain cancer. In spite of intensive therapy, the
      prognosis of patients with glioblastoma is very poor. To discover novel
      therapeutic agents, we screened a combinatorial compound library containing 372
      thiazolidinone compounds using U87MG human glioblastoma cells. (2E,5Z)-5-(2
      hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one (HBPT) was
      identified as the most potent anti-glioblastoma compound. HBPT inhibits U87MG
      human glioblastoma cell proliferation with an IC50 of 20 MUM, which is almost 5
      fold more potent than temozolomide (a widely used drug for treating malignant
      glioma in the clinic). Mechanistic investigation demonstrated that HBPT is a
      novel microtubule-depolymerizing agent, which arrests cancer cells at the G2/M
      phase of the cell cycle and induces cell apoptosis. In the mouse U87MG xenograft
      model, HBPT elicits a robust tumor inhibitory effect. More importantly, no
      obvious toxicity was observed for HBPT therapy in animal experiments. These
      findings indicate that HBPT has the potential to be developed as a novel agent
      for the treatment of glioblastoma. [Supplementary Tables: available only at
      http://dx.doi.org/10.1254/jphs.13064FP].

PMID- 23877017
TI  - Reaction of proton pump inhibitors with model peptides results in novel products.
AB  - The proposed mechanism for proton pump inhibitors (PPIs) is that PPIs are
      activated at low pH to the sulfenamide form, which reacts with the sulfhydryl
      group of cysteine(s) at the active site of the proton pump, to produce reducible
      disulfide-bonded PPI-proton pump conjugates. However, this mechanism cannot
      explain the observations that some PPI-protein conjugates are irreducible. This
      study was designed to investigate the chemistry of the irreducible conjugates by
      mass spectrometry, using three PPIs and 17 cysteine-containing peptides. While
      some peptides favored the formation of reducible PPI-peptide adduct, the other
      peptides mainly produced irreducible adducts. Characterization of the irreducible
      adduct revealed that the irreducible bonding required the participation of both a
      sulfhydryl group and a nearby primary amino group. High resolution mass
      spectrometry suggested a molecular structure of the irreducible adduct. These
      results suggested a reaction mechanism in which the PPI pyridone form reacted
      with an amino group and a sulfhydryl group to form an irreducible adduct. The
      irreducible adduct becomes the dominant product over time because of the
      irreversible nature of the pyridone-mediated reaction. These findings may explain
      the irreducible inhibition of H/K-ATPase by PPIs and their relatively slow
      biological turnover in vivo. [Supplementary materials: available only at
      http://dx.doi.org/10.1254/jphs.13058FP].

PMID- 23877019
TI  - Use of discrete event simulation to improve a mental health clinic.
AB  - OBJECTIVE: To improve clinic design, trial-and-error is commonly used to discover
      strategies that lead to improvement. Our goal was to predict the effects of
      various changes before undertaking them. METHOD: Systems engineers collaborated
      with staff at an integrated primary care-mental health care clinic to create a
      computer simulation that mirrored how the clinic currently operates. We then
      simulated hypothetical changes to the staffing to understand their effects on
      percentage of patients seen outside scheduled clinic hours and service completion
      time. RESULTS: We found that, out of the change options being considered by the
      clinic, extending daily clinic hours by two and including an additional
      psychiatrist are likely to result in the greatest incremental decreases in
      patients seen outside clinic hours and in service time. CONCLUSION: Simulation in
      partnership with engineers can be an attractive tool for improving mental health
      clinics, particularly when changes are costly and thus trial-and-error is not
      desirable.

PMID- 23877020
TI  - Comparison of osteoprotegerin and vascular endothelial growth factor in
      normoalbuminuric Type 1 diabetic and control subjects.
AB  - BACKGROUND: The aim of the current study was to evaluate the association of
      osteoprotegerin and vascular endothelial growth factor (VEGF) with glycemic
      indices and diabetes status. METHODS: A total of 44 normoalbuminuric Type 1
      diabetic patients and 44 healthy control subjects, matched for age, body mass
      index, sex ratio, and lipid measures were enrolled. Univariate and multivariate
      logistic regression analyses were used to determine the association of
      osteoprotegerin and VEGF with diabetes status. Further, linear regression
      analysis was performed to investigate the roles of osteoprotegerin and VEGF as
      determinants of glycated hemoglobin (HbA1c). RESULTS: Osteoprotegerin and VEGF
      were significantly elevated in diabetic subjects (2.76+/-0.85 vs 2.26+/-0.75
      pmol/l and 187.1+/-92.7 vs 125.9+/-52.3 pg/ml, respectively, p<0.01) and were
      positively correlated with glycemic indices (i.e. fasting plasma glucose and
      HbA1c, p<0.001). After controlling for possible confounding factors, odds ratios
      (confidence interval) of osteoprotegerin and VEGF for diabetes were 2.532 (1.003
      6.392) and 1.021 (1.002-1.041), respectively (p<0.05). Further, linear regression
      analysis revealed that the association of osteoprotegerin with HbA1c is
      independent of VEGF and vice versa (p<0.001). CONCLUSION: Osteoprotegerin and
      VEGF are elevated in normoalbuminuric Type 1 diabetic subjects and are
      independently associated with glycemic indices and diabetes status.

PMID- 23877021
TI  - Endocrinology and art. Cubist portrait of acromegalic woman.

PMID- 23877022
TI  - Lamotrigine for intractable migraine-like headaches in Sturge-Weber syndrome.
AB  - We herein report that naratriptan remarkably improved intractable migraine-like
      headaches in a patient with Sturge-Weber syndrome (SWS) despite his past history
      of cerebral infarction. In addition, lamotrigine had a prophylactic effect on his
      visual aura and headaches. An 18-year-old male patient with SWS had intractable
      migraine-like headaches every several months from the age of 3years. His migraine
      like headaches were characterized by pulsating attacks preceded by left
      homonymous hemianopsia, which persisted after headache disappearance. In
      addition, after 14years of age, the pulsating headaches were preceded by
      photophobia without homonymous hemianopsia and occurred almost daily. Headache
      pains were not improved by acetaminophen or loxoprofen sodium hydrate.
      Furthermore, various prophylactic drugs were ineffective. After obtaining
      informed consent, naratriptan was administered. The pain severity was reduced and
      the duration of headache with homonymous hemianopsia was shortened from several
      days to several hours. Interestingly, naratriptan also shortened the duration of
      homonymous hemianopsia to several hours. We confirmed that his headache attacks
      were not epileptic seizures by ictal electroencephalography. However, 25mg/day of
      lamotrigine had a prophylactic effect on the frequency of headache. Moreover,
      lamotrigine led to complete remission of his headache without homonymous
      hemianopsia. Lamotrigine may have an advantage in terms of reducing the risk of
      cerebrovascular disease caused by migraine-like headaches and the use of
      triptans. The most effective management for migraine-like headaches in patients
      with SWS has not been established. Lamotrigine is a potentially effective option
      for patients with SWS with migraine-like headaches. 

PMID- 23877023
TI  - Cyclooxygenase-2 mediates induction of the renal stanniocalcin-1 gene by arginine
      vasopressin.
AB  - In rats and mice, the renal stanniocalcin-1 (STC-1) gene is expressed in most
      nephron segments, but is differentially induced in response to dehydration. In
      cortical segments STC-1 mRNA levels are upregulated by the hypertonicity of
      dehydration, while hypovolemia causes gene induction in the inner medulla
      (papilla). In both cases induction is mediated by arginine vasopressin (AVP)
      acting via the V2 receptor (V2R). The intent of STC-1 gene upregulation during
      dehydration has yet to be established. Therefore, to narrow down the range of
      possible actions, we mapped out the pathway by which V2R occupancy upregulates
      the gene. V2R occupancy activates two different renal pathways in response to
      dehydration. The first is antidiuretic in nature and is mediated by direct V2R
      occupancy. The second pathway is indirect and counter-regulates AVP-mediated
      antidiuresis. It involves COX-2 (cyclooxygenase-2) and the prostanoids, and is
      activated by the V2R-mediated rise in medullary interstitial osmolality. The
      resulting prostanoids counter-regulate AVP-mediated antidiuresis. They also
      upregulate renal cytoprotective mechanisms. The present studies employed models
      of COX inhibition and COX gene deletion to address the possible involvement of
      the COX pathway. The results showed that both general and specific inhibitors of
      COX-2 blocked STC-1 gene induction in response to dehydration. Gene induction in
      response to dehydration was also abolished in COX-2 null mice (cortex and
      papilla), but not in COX-1 null mice. STC-1 gene induction in response to V2R
      occupancy was also uniquely abolished in COX-2 nulls (both regions). These
      findings therefore collectively suggest that AVP-mediated elevations in STC-1
      gene expression are wholly dependent on functional COX-2 activity. As such, a
      permissive role for STC-1 in AVP-mediated antidiuresis can be ruled out, and its
      range of possible actions has been narrowed down to AVP counter-regulation and
      renal cytoprotection. 

PMID- 23877024
TI  - A review of inpatient urology consultations in an Irish tertiary referral centre.
AB  - INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad
      medical and surgical subspecialty services. We retrospectively audited the
      pattern of inpatient consultations from all specialities within our institution
      to the urology department over a 1-year period. METHODS: All consultations to the
      urology service were identified from our computerised inpatient consultation
      system from July 2010 to June 2011. Follow up data on investigations,
      interventions and subsequent outpatient appointments were also identified by
      review of individual patient discharge letters. RESULTS: Seven hundred and twenty
      five inpatient consultations were received over the period. The male to female
      ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent
      of referrals were from medical sub-specialities, most commonly nephrology (17%),
      gastroenterology (11%) and respiratory medicine (9%). The remainder were from
      general surgery (16%) and other surgical sub specialities (11%). Interns (66%)
      and senior house officers (SHO) (28%) communicated the majority of consults. Male
      lower urinary tract/benign prostate related issues resulted in 25% of all
      consultations. Less than half of consults (47%) resulted in interventions
      initiated by urology, most commonly of which were catheter insertions (48%) and
      endoscopic procedures (35%). Only 43% of consultations were followed up in the
      outpatients setting. CONCLUSIONS: Inpatient consultations constitute a
      significant workload for urology services. The majority of these referrals did
      not require any urological intervention and could have been seen routinely in the
      outpatient setting. Providing structured referral guidelines and achieving better
      communication with referring teams may help to optimise this service.

PMID- 23877025
TI  - ED50 of sevoflurane for LMA Supreme insertion: reliability!

PMID- 23877026
TI  - Secondary metabolites of a mangrove endophytic fungus Aspergillus terreus (No.
      GX7-3B) from the South China Sea.
AB  - The mangrove endophytic fungus Aspergillus terreus (No. GX7-3B) was cultivated in
      potato dextrose liquid medium, and one rare thiophene compound (1), together with
      anhydrojavanicin (2), 8-O-methylbostrycoidin (3), 8-O-methyljavanicin (4),
      botryosphaerone D (5), 6-ethyl-5-hydroxy-3,7-dimethoxynaphthoquinone (6),
      3beta,5alpha-dihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (7),
      3beta,5alpha,14alpha-trihydroxy-(22E,24R)-ergosta-7, 22-dien-6-one (8), NGA0187
      (9) and beauvericin (10), were isolated. Their structures were elucidated by
      analysis of spectroscopic data. This is the first report of a natural origin for
      compound 6. Moreover, compounds 3, 4, 5, 7, 8 and 10 were obtained from marine
      microorganism for the first time. In the bioactive assays in vitro, compounds 2,
      3, 9 and 10 displayed remarkable inhibiting actions against alpha
      acetylcholinesterase (AChE) with IC50 values 2.01, 6.71, 1.89, and 3.09 MUM,
      respectively. Furthermore, in the cytotoxicity assays, compounds 7 and 10
      exhibited strong or moderate cytotoxic activities against MCF-7, A549, Hela and
      KB cell lines with IC50 values 4.98 and 2.02 (MCF-7), 1.95 and 0.82 (A549), 0.68
      and 1.14 (Hela), and 1.50 and 1.10 MUM (KB), respectively; compound 8 had weak
      inhibitory activities against these tumor cell lines; compounds 1, 2, 3, 4, 5, 6
      and 9 exhibited no inhibitory activities against them. 

PMID- 23877028
TI  - Shoulder kinematics is not influenced by external load during elevation in the
      scapular plane.
AB  - The current study aimed to compare the shoulder kinematics (3D scapular
      orientation, scapular angular displacement and scapulohumeral rhythm) of
      asymptomatic participants under unloaded and loaded conditions during unilateral
      shoulder elevation in the scapular plane. We used a repeated-measures design with
      a convenience sample. Eleven male participants with an age range of 21-28 years
      with no recent history of shoulder injury participated in the study. The
      participants performed isometric shoulder elevation from a neutral position to
      approximately 150 degrees of elevation in the scapular plane in intervals of
      approximately 30 degrees during unloaded and loaded conditions. Shoulder
      kinematic data were obtained with videogrammetry. During shoulder elevation, the
      scapula rotated upwardly and externally, and tilted posteriorly. The addition of
      an external load did not affect 3D scapular orientation, scapular angular
      displacement, or scapulohumeral rhythm throughout shoulder elevation (P > .05).
      In clinical practice, clinicians should expect to observe upward and external
      rotation and posterior tilt of the scapula during their assessments of shoulder
      elevation. Such behavior was not influenced by an external load normalized to 5%
      of body weight when performed in an asymptomatic population. 

PMID- 23877027
TI  - Fish oil slows prostate cancer xenograft growth relative to other dietary fats
      and is associated with decreased mitochondrial and insulin pathway gene
      expression.
AB  - BACKGROUND: Previous mouse studies suggest that decreasing dietary fat content
      can slow prostate cancer (PCa) growth. To our knowledge, no study has yet
      compared the effect of multiple different fats on PCa progression. We sought to
      systematically compare the effect of fish oil, olive oil, corn oil and animal fat
      on PCa progression. METHODS: A total of 96 male severe combined immunodeficient
      mice were injected with LAPC-4 human PCa cells. Two weeks following injection,
      mice were randomized to a Western diet based on fish oil, olive oil, corn oil or
      animal fat (35% kilocalories from fat). Animals were euthanized when tumor
      volumes reached 1000 mm(3). Serum was collected at death and assayed for PSA,
      insulin, insulin-like growth factor-1 (IGF-1), IGF-1-binding protein-3 and
      prostaglandin E-2 (PGE-2) levels. Tumors were also assayed for PGE-2 and
      cyclooxygenase-2 levels, and global gene expression was analyzed using Affymetrix
      microarrays. RESULTS: Mice weights and tumor volumes were equivalent across
      groups at randomization. Overall, fish oil consumption was associated with
      improved survival relative to other dietary groups (P=0.014). On gene expression
      analyses, the fish oil group had decreased signal in pathways related to
      mitochondrial physiology and insulin synthesis/secretion. CONCLUSIONS: In this
      xenograft model, we found that consuming a diet in which fish oil was the only
      fat source slowed tumor growth and improved survival compared with that in mice
      consuming diets composed of olive oil, corn oil or animal fat. Although prior
      studies showed that the amount of fat is important for PCa growth, this study
      suggests that the type of dietary fat consumed may also be important.

PMID- 23877029
TI  - A new ladder-type benzodi(cyclopentadithiophene)-based donor-acceptor polymer and
      a modified hole-collecting PEDOT:PSS layer to achieve tandem solar cells with an
      open-circuit voltage of 1.62 V.
AB  - We have developed a new ladder-type conjugated polymer and a robust
      interconnecting layer (ICL) integrating a hole-collecting m-PEDOT:PSS layer with
      an electron-collecting ZnO layer. The inverted device using exhibited a high
      power conversion efficiency (PCE) of 5.76% with a Voc of 0.81 V, a Jsc of 12.82
      mA cm(-2), and a FF of 55.5%. The inverted tandem device incorporating the and
      ICL achieves a Voc of 1.62 V leading to a PCE of 7.08%.

PMID- 23877031
TI  - Nanosized transition metals in controlled environments of phyllosilicate
      mesoporous silica composites as highly thermostable and active catalysts.
AB  - Stabilization of transition metals in nano-phyllosilicate phases generated by
      digestion of mesoporous silica is reported as an efficient route for the
      formation of highly dispersed metallic nanoparticles with outstanding catalytic
      activity. 

PMID- 23877030
TI  - DNA electroporation in rabbits as a method for generation of high-titer
      neutralizing antisera: examples of the botulinum toxins types A, B, and E.
AB  - Raising high titer antibodies in animals is usually performed by protein
      immunization, which requires the long and sometimes difficult step of production
      of the recombinant protein. DNA immunization is an alternative to recombinant
      proteins, only requiring the building of an eukaryotic expression plasmid. Thanks
      to efficient DNA delivery techniques such as in vivo electroporation, DNA
      vaccination has proven useful the last few years. In this work, we have shown
      that it is possible to raise very high antibody titers in rabbit by DNA
      electroporation of an antigen encoding plasmid in the skeletal muscle with the
      right set of electrodes and rabbit strain. In a model of botulinum toxins types A
      and E, the neutralizing titers obtained after three treatments were high enough
      to fit the European Pharmacopeia, while it did not for type B toxin. Furthermore,
      the raised antibodies have high avidity and are suitable for in vitro and in vivo
      immunodetection of proteins. 

PMID- 23877032
TI  - Relationship between asymmetry of quiet standing balance control and walking post
      stroke.
AB  - Spatial and temporal gait asymmetry is common after stroke. Such asymmetric gait
      is inefficient, can contribute to instability and may lead to musculoskeletal
      injury. However, understanding of the determinants of such gait asymmetry remains
      incomplete. The current study is focused on revealing if there is a link between
      asymmetry during the control of standing balance and asymmetry during walking.
      This study involved review of data from 94 individuals with stroke referred to a
      gait and balance clinic. Participants completed three tests: (1) walking at their
      usual pace; (2) quiet standing; and (3) standing with maximal loading of the
      paretic side. A pressure sensitive mat recorded placement and timing of each
      footfall during walking. Standing tests were completed on two force plates to
      evaluate symmetry of weight bearing and contribution of each limb to balance
      control. Multiple regression was conducted to determine the relationships between
      symmetry during standing and swing time, stance time, and step length symmetry
      during walking. Symmetry of antero-posterior balance control and weight bearing
      were related to swing time and step length symmetry during walking. Weight
      bearing symmetry, weight-bearing capacity, and symmetry of antero-posterior
      balance control were related to stance time symmetry. These associations were
      independent of underlying lower limb impairment. The results support the
      hypothesis that impaired ability of the paretic limb to control balance may
      contribute to gait asymmetry post-stroke. Such work suggests that rehabilitation
      strategies that increase the contribution of the paretic limb to standing balance
      control may increase symmetry of walking post-stroke.

PMID- 23877033
TI  - Short-term differential training decreases postural sway.
AB  - Differential training has been shown to enhance motor learning in sports skills.
      In the present study differential training was applied to the minimization of
      postural sway. A differential training group performed 15 one minute practice
      trials, each with different postural movement instructions. A repetitive practice
      group performed 15 trials standing as still as possible for one minute. Pre- and
      post-tests were performed standing as still as possible in 1 and 2-leg stance.
      Accelerometry data were collected approximately at the level of the center of
      mass (COM) and at the head. The root mean square jerk (RMSJ) of movement at the
      COM and head was estimated for the anteroposterior and mediolateral axes of
      motion. A significant Group * Test interaction revealed that the differential
      training led to lower anteroposterior RMSJ on the post-test than on the Pre-test
      in both the 1 and 2-leg stance tasks. A significant Group * Effector * Test
      interaction revealed that the decrease in anteroposterior RMSJ with differential
      training occurred in the RMSJ of the head but not the COM. The repetitive
      practice did not lead to a significant change in anteroposterior RMSJ at either
      the COM or the head. Neither form of training led to a significant change in
      mediolateral RMSJ. The results indicated that differential training can enhance
      motor learning not only in complex sports skills but in relatively simple motor
      tasks such as maintaining quiet stance.

PMID- 23877034
TI  - A model of postural coordination dynamics.
AB  - Prior research has shown that voluntary postural movement is characterized by
      stable in-phase and antiphase hip-ankle coordination modes. Prior modeling of
      coordination dynamics does not capture the stable fixed-points, phase transitions
      and hysteresis found in hip-ankle coordination. In this article a model was
      created to capture the dynamics of hip-ankle postural coordination. The present
      model follows the synergetic approach and uses two nonlinear oscillators to
      capture the dynamics of hip-ankle coordination. Terms for symmetry breaking and
      additive stochastic noise are included in the model. The model captures phase
      transitions from in-phase to antiphase coordination as movement frequency is
      scaled up and from antiphase to in-phase coordination as movement frequency is
      scaled down. The model also exhibits hysteresis, with phase transitions occurring
      at different movement frequencies as the control parameter is scaled up and down.

PMID- 23877035
TI  - Pediatric resident perceptions of public health education: learner-based insights
      into curriculum design and implementation.
AB  - OBJECTIVE: The purpose of this research was to evaluate a public health
      curriculum for pediatric residents from the learners' perspective, exploring
      resident attitudes, insights, and recommendations as to the most effective and
      learner-centric approaches to curriculum design and implementation in the context
      of graduate medical education. METHODS: Forty-five of 59 Children's Hospital of
      The Kings' Daughters (CHKD) residents participated in focus groups and individual
      interviews. All sessions took place between June and July 2012 and were
      audiorecorded, transcribed, and coded for major themes using NVivo software.
      RESULTS: The 5 major themes identified by this study included: 1) perceptions of
      public health relevance and impact, 2) time and competing priorities, 3) speaker
      audience harmonization, 4) the need for practical solutions, and 5) individual
      tailoring. Study results paint a distinctive picture of residents' ideal public
      health curriculum-a less structured, more individualized educational opportunity
      that prioritizes small group discussions, maximizes speaker-audience
      interactions, and details a wide array of specific community-based programs and
      resources available to pediatricians and their patients. CONCLUSIONS: The learner
      needs identified through this research suggest that effective public health
      training for residents would include protected time for public health
      instruction, faculty development workshops, linkages with appropriate local
      organizations, and opportunities for each resident to pursue his or her own
      projects. Residencies that wish to address learner preferences in the development
      and realization of public health training would benefit from considering these
      characteristics in designing their curriculum.

PMID- 23877036
TI  - Disruption of TAB1/p38alpha interaction using a cell-permeable peptide limits
      myocardial ischemia/reperfusion injury.
AB  - Targeting the adaptor protein (transforming growth factor-beta (TGF-beta)
      activated protein kinase 1 (TAK1)-binding protein 1) (TAB1)-mediated non
      canonical activation of p38alpha to limit ischemia/reperfusion (I/R) injury after
      an acute myocardial infarction seems to be attractive since TAB1/p38alpha
      interaction occurs specifically in very limited circumstances and possesses
      unique structural basis. However, so far no TAB1/p38alpha interaction inhibitor
      has been reported due to the limited knowledge about the interfaces. In this
      study, we sought to identify key amino acids essential for the unique mode of
      interaction with computer-guided molecular simulations and molecular docking.
      After validation of the predicted three-dimensional (3-D) structure of
      TAB1/p38alpha complex, we designed several peptides and evaluated whether they
      could block TAB1/p38alpha interaction with selectivity. We found that a cell
      permeable peptide worked as a selective TAB1/p38alpha interaction inhibitor and
      decreased myocardial I/R injury. To our knowledge, this is the first
      TAB1/p38alpha interaction inhibitor.

PMID- 23877038
TI  - Phytotoxicity and oxidative stress effect of 1-octyl-3-methylimidazolium chloride
      ionic liquid on rice seedlings.
AB  - The effects of the ionic liquid 1-octyl-3-methylimidazolium chloride ([OMIM]Cl)
      was studied in hydroponically grown rice seedlings. Observed effects included
      increased root length and weight at concentrations of 0.1 mg/L [OMIM]Cl, however,
      as concentrations increased a reversed response was observed where roots and
      stems grew shorter and the weight decreased. The inhibitory concentration 50
      (IC50,5d) values for root length and stem length were 0.59 mg/L and 0.70 mg/L,
      respectively. The Hill reaction activity and root system activity in [OMIM]Cl
      treated rice seedlings were observed to be lower than the controls, however, root
      membrane permeability increased. The antioxidant enzyme activity in roots
      decreased, while in leaves there was an initial stimulation followed by a
      decrease. Malondialdehyde (MDA) content was found to be greater in seedlings
      subjected to [OMIM]Cl treatment. The cellular structures, such as chloroplasts,
      mitochondria and rough endoplasmic reticulum in rice root and leaf cells were
      affected at concentrations of 0.6 mg/L [OMIM]Cl.

PMID- 23877039
TI  - An SPE LC-MS/MS method for the analysis of human and veterinary chemical markers
      within surface waters: an environmental forensics application.
AB  - In this study, the use of co-occurring discriminators of sewage and manure was
      assessed as a potential way to disentangle sewage and manure sources. A suite of
      human and veterinary derived chemical markers, which includes pharmaceuticals and
      compound such as food additives, has been identified for this purpose. The suite
      was selected in such a manner as to provide additional source characterisation,
      e.g. differentiating raw versus treated sewage inputs. An SPE-LC-MS/MS method was
      developed and validated for the determined suite of chemical markers with a
      detection limit of up to 50 pg L(-1). This represents one of the lowest limits of
      detection for pharmaceuticals reported in literature. To illustrate the
      suitability of the proposed method to differentiate sewage and manure inputs to
      surface water bodies, results from surface water samples collected at monitoring
      sites corresponding to specific land use types within Ireland are discussed.

PMID- 23877040
TI  - Baseline concentrations of strontium and 90Sr in seawater from the northern Gulf.
AB  - Baseline concentration of strontium and Sr-90 in Gulf is presented. The strontium
      concentration is much higher than reported for other oceanic waters, while the Sr
      90 concentration is low at 0.7-1.0 mBq l(-1), that represents the background
      level following nuclear tests and can be used as an effective tracer in case of
      any radioactive release in the region. The strontium concentration is primarily
      related to the increasing salinity off the Gulf coast.

PMID- 23877041
TI  - Editorial: dental education--are we losing track? The need to revisit disease
      control-based therapy understanding.

PMID- 23877043
TI  - Topological phase transition induced by spin-orbit coupling in bilayer graphene.
AB  - We study the topological phase transition in biased bilayer graphene in the
      presence of intrinsic and Rashba spin-orbit couplings. The system exhibits a
      complicated topological phase transition depending on the given parameters. The
      topological phase transition between these phases is always accompanied by the
      bulk gap closing and reopening, and can be realized by tuning the bias voltage.
      The stability of these topological phases are also investigated. We find that the
      weak (strong) topological insulator phase remains stable under a finite exchange
      field provided that the effect of intrinsic (Rashba) spin-orbit coupling is
      dominant, and this also holds for the quantum valley Hall phase if the spatial
      inversion symmetry breaking overcomes the time-reversal symmetry breaking. 

PMID- 23877042
TI  - CIMT 2013: advancing targeted therapies--report on the 11th Annual Meeting of the
      Association for Cancer Immunotherapy, May 14-16 2013, Mainz, Germany.
AB  - The 11th Annual Meeting of Association for Cancer Immunotherapy (CIMT) welcomed
      more than 700 scientists around the world to Mainz, Germany and continued to be
      the largest immunotherapy meeting in Europe. Renowned speakers from various
      fields of cancer immunotherapy gave lectures under CIMT2013's tag: "Advancing
      targeted therapies" the highlights of which are summarized in this meeting
      report. 

PMID- 23877045
TI  - Acute injury risk and severity in indoor climbing-a prospective analysis of
      515,337 indoor climbing wall visits in 5 years.
AB  - OBJECTIVE: Rock climbing's popularity continues to rise, with people of all ages
      regularly participating in the sport. Climbing literature suggests climbers get
      injured mostly in their upper extremities. Most studies on climbing injury
      analysis are conducted retrospectively, with all the inherent problems of a
      retrospective setup (no exact time collection, biased injury perception, etc).
      Prospective data are still missing. METHODS: We prospectively evaluated all
      attendees of a major German indoor climbing gym in Stuttgart, Germany, with
      bouldering and lead climbing facilities. Attendee's age, sex, and time spent
      climbing were electronically recorded on each visit. All acute injuries were
      graded using the Medical Commission of the Union Internationale des Associations
      d'Alpinisme Score. Injury cause, belayers' and climbers' experience, and outcome
      were additionally analyzed. RESULTS: During a 5-year period (2007-2011), 515,337
      visits to the climbing wall were registered, of which 63.6% were by male
      visitors, 36.4% female, within an age of 8-80 years (median, 34 years). The
      average time of climbing was 2 hours 47 minutes. Thirty climbing injuries were
      recorded, 22 were in male and 8 in female climbers with a total mean age of 27.5
      +/- 10.6 years. Acute injuries happened in 6 cases while bouldering, in 16 cases
      while lead climbing, in 7 cases while top roping, and in 1 case as a third person
      (not climbing or belaying) while watching another climber. Bouldering injuries
      were mostly the result of falls onto the mat, whereas in lead and top rope
      climbing various scenarios happened. Fifteen (50%) injuries were Medical
      Commission of the Union Internationale des Associations d'Alpinisme grade 2, 13
      (43%) were grade 3, and 2 (7%) were grade 4, with no fatalities. The overall
      injury rate was 0.02 injuries per 1000 hours of climbing activities. CONCLUSIONS:
      This was the first study to accurately record time spent indoor climbing
      digitally and evaluate the acute injuries prospectively in a large cohort. There
      were few injuries sustained, suggesting indoor climbing has a low risk of acute
      injury per 1000 hours of participation. The injuries were of minor to moderate
      injury severity, and no fatalities occurred. Several injuries could have been
      avoided, and further injury-prevention concepts should be developed.

PMID- 23877046
TI  - A Zn(2+)-responsive highly sensitive fluorescent probe and 1D coordination
      polymer based on a coumarin platform.
AB  - A coumarin-based Schiff base (receptor 1) exhibited fluorescence enhancement
      selectively with Zn(2+) at a nanomolar level in near-aqueous medium (EtOH-H2O;
      1:1, v/v). The response was instantaneous with a detection limit of 3.26 * 10(-9)
      M. The sensing event is supposed to incorporate a combinational effect of
      intramolecular charge transfer (ICT), chelation-enhanced fluorescence (CHEF) and
      C[double bond, length as m-dash]N isomerization mechanisms. Various spectroscopic
      methods, viz. IR, UV-visible, fluorescence and NMR in association with single
      crystal XRD studies, were used for thorough investigation of the structure of
      receptor 1 as well as of the sensing event. The Zn(2+) complex of receptor 1
      exhibited a very nice 1D chain coordination polymeric framework in its single
      crystal XRD.

PMID- 23877048
TI  - Synthesis and biological evaluation of a new acyclic pyrimidine derivative as a
      probe for imaging herpes simplex virus type 1 thymidine kinase gene expression.
AB  - With the idea of finding a more selective radiotracer for imaging herpes simplex
      virus type 1 thymidine kinase (HSV1-tk) gene expression by means of positron
      emission tomography (PET), a novel [18F]fluorine radiolabeled pyrimidine with 4
      hydroxy-3-(hydroxymethyl)butyl side chain at N-1 (HHB-5-[18F]FEP) was prepared
      and evaluated as a potential PET probe. Unlabeled reference compound, HHB-5-FEP,
      was synthesized via a five-step reaction sequence starting from 5-(2
      acetoxyethyl)-4-methoxypyrimidin-2-one. The radiosynthesis of HHB-[18F]-FEP was
      accomplished by nucleophilic radiofluorination of a tosylate precursor using
      [18F]fluoride-cryptate complex in 45% +/- 4 (n = 4) radiochemical yields and high
      purity (>99%). The biological evaluation indicated the feasibility of using HHB-5
      [18F]FEP as a PET radiotracer for monitoring HSV1-tk expression in vivo.

PMID- 23877047
TI  - Changes in traffic exposure and the risk of incident myocardial infarction and
      all-cause mortality.
AB  - BACKGROUND: Traffic-related exposures, such as air pollution and noise, have been
      associated with increased cardiovascular morbidity and mortality. Few studies,
      however, have been able to examine the effects of changes in exposure on changes
      in risk. Our objective was to explore the associations of changes in traffic
      exposure with changes in risk between 1990 and 2008 in the Nurses' Health Study.
      METHODS: Incident myocardial infarction (MI) and all-cause mortality were
      prospectively identified. As a proxy for traffic exposure, we calculated
      residential distance to roads at all residential addresses 1986-2006 and
      considered addresses to be "close" or "far" based on distance and road type. To
      examine the effect of changes in exposure, each consecutive pair of addresses was
      categorized as: (1) consistently close, (2) consistently far, (3) change from
      close to far, and (4) change from far to close. We also examined the change in
      NO2 levels between address pairs. RESULTS: In time-varying Cox proportional
      hazards models adjusted for a variety of risk factors, women living at residences
      consistently close to traffic were at a higher risk of an incident MI (hazard
      ratio [HR] = 1.11; 95% confidence interval [CI] = 1.01-1.22) and a higher risk of
      all-cause mortality (1.05; 1.00-1.10), compared with those consistently far. The
      highest risks were seen among women who moved from being far from traffic to
      close (incident MI: HR = 1.50 [95% CI = 1.11-2.03]; all-cause mortality: HR =
      1.17 [95% CI = 1.00-1.37]). Each 1 ppb increase in NO2 compared with the previous
      address was associated with a HR = 1.22 for incident MI (95% CI = 0.99-1.50) and
      1.03 for all-cause mortality (95% CI = 0.92-1.15). CONCLUSIONS: Our results
      suggest that changes in traffic exposure (measured as roadway proximity or change
      in NO2 levels) are associated with changes in risk of MI and all-cause mortality.

PMID- 23877049
TI  - Synthesis and bioassay of a new class of furanyl-1,3,4-oxadiazole derivatives.
AB  - Tyrosinase enzyme is a monophenol monoxygenase enzyme, which plays an important
      role in human as a rate limiting step enzyme for different specific metabolic
      pathways, as well as its useful application in industry and agriculture. So this
      study was carried out to test the effect of newly prepared compounds containing
      1,3,4-oxadiazoles with different substituted groups on tyrosinase enzyme
      activity, hoping to use them in the treatment of some diseases arising from
      tyrosinase activity disorders such as Parkinson's disease, schizophrenia, autism,
      attention deficit, hyperactivity disorder, and cancer. 

PMID- 23877050
TI  - Elaboration of stable and antibody functionalized positively charged colloids by
      polyelectrolyte complexation between chitosan and hyaluronic acid.
AB  - In this study, we describe the elaboration of multifunctional positively charged
      polyelectrolyte complex (PEC) nanoparticles, designed to be stable at
      physiological salt concentration and pH, for effective targeted delivery. These
      nanoparticles were obtained by charge neutralization between chitosan (CS) as
      polycation and hyaluronic acid (HA) as polyanion. We showed that the course of
      the complexation process and the physico-chemical properties of the resulting
      colloids were impacted by (i) internal parameters such as the Degree of
      Acetylation (DA, i.e., the molar ration of acetyl glucosamine residues) and molar
      mass of CS, the HA molar mass and (ii) external parameters like the charge mixing
      ratio and the polymer concentrations. As a result, nonstoichiometric colloidal
      PECs were obtained in water or PBS (pH 7.4) and remained stable over one month.
      The polymer interactions were characterized by thermal analysis (DSC and TGA) and
      the morphology was studied by scanning electron microscopy. A model antibody,
      anti-ovalbumine (OVA) immunoglobulin A (IgA) was sorbed on the particle surface
      in water and PBS quantitatively in 4 h. The CS-HA/IgA nanoparticles average size
      was between 425-665 nm with a positive zeta potential. These results pointed out
      that CS-HA can be effective carriers for use in targeted drug delivery. 

PMID- 23877051
TI  - A novel surgery-like strategy for droplet coalescence in microchannels.
AB  - We report an innovative and efficient surgery-like strategy for achieving the
      coalescence of surfactant-stabilized droplets in microchannels. As pairs of
      preformed droplets flow across a micro-lancet, with a suitable surface
      wettability, in a converging microchannel simultaneously, their surfaces are
      scratched by the micro-lancet, which causes temporarily local scattering of
      surfactants, and thus induces their coalescence by joining up their scratched
      wounds. Our approach shows highly controllable flexibility and stability. We
      demonstrate this by controlling the coalescence of emulsion droplets with
      different numbers and complex structures. This surgery-like strategy is totally
      passive and has great potential in myriad applications including micro-reaction,
      high-throughput injection, and multiple emulsion formation, etc. 

PMID- 23877053
TI  - Perceived access and actual intake of healthy diets among households in
      vulnerable Salvadoran communities.
AB  - OBJECTIVE: This study aimed to examine the dietary intake of Salvadoran
      households according to perceived access to healthy meals (PAHD), and to identify
      household characteristics associated with diet quality and PAHD. METHODS:
      Secondary data analysis with a sample of 139 Salvadoran households from resource
      poor communities in El Salvador. Chi-square tests and ANOVA were used to assess
      differences in dietary intake across households classified according to PAHD.
      RESULTS: High-PAHD households had higher women's education, household food
      security levels, overall diet quality, and variety, and higher intakes of animal
      products, fats, cholesterol, vitamin C, and sodium (P < .05). Diet quality was
      not associated with the household characteristics studied. CONCLUSIONS AND
      IMPLICATIONS: Overall diet quality was associated with higher levels of PAHD, but
      some differences in intakes were not as expected, such as higher intakes in foods
      and nutrients associated with low-quality diets, among high PAHD households.

PMID- 23877052
TI  - Making compromises: a qualitative study of sugar consumption behaviors during
      pregnancy.
AB  - OBJECTIVE: To explore influences on women's sugar consumption behaviors during
      pregnancy. DESIGN: Focused ethnography guided this qualitative study. Contrasting
      experiences between women with varying sugar intakes were investigated using semi
      structured interviews. SETTING: Metropolitan area, Canada. PARTICIPANTS: Fifteen
      women with varying intakes of added sugar, who were in the third trimester of
      their first pregnancy, participated in this study. PHENOMENON OF INTEREST: Sugar
      consumption behaviors during pregnancy. ANALYSIS: Interviews were audio-recorded,
      transcribed, and analyzed using qualitative content analysis to inductively
      derive themes. RESULTS: Pregnant women increased their intake of sugars in an
      effort to achieve a compromise between meeting nutrition recommendations,
      lifestyle adjustments, physical symptoms, and cultural norms. Physical symptoms,
      lack of nutritional guidance, and social pressures were identified as barriers to
      achieving a diet low in sugars, whereas implementing dietary strategies guided by
      nutritional knowledge was a facilitator. CONCLUSIONS AND IMPLICATIONS: This
      research provides insights that may be used to design effective interventions to
      improve maternal health. Strategies to help pregnant women achieve a healthy diet
      and limit sugar intake should be guided by nutritional knowledge, dietary
      awareness, and internal motivations to engage in healthy dietary changes.

PMID- 23877054
TI  - Soft drink consumption patterns among Western Australians.
AB  - OBJECTIVE: To examine soft drink consumption across age, gender, socioeconomic,
      and body weight status groups within an adolescent and adult population. DESIGN:
      Cross-sectional telephone survey. PARTICIPANTS: Western Australian residents (n =
      1,015) aged 16-65 years, selected through random dialing. VARIABLES MEASURED:
      Frequency and quantity of sugar-sweetened and diet soft drinks consumption,
      sociodemographic characteristics. ANALYSIS: The Kruskal-Wallis test of
      association for non-parametric data was used to explore differences in quantity
      of soft drinks consumed. Logistic regression models used to explore type of soft
      drinks consumed by sociodemographic factors and weight status. RESULTS: A greater
      proportion of females consumed no soft drinks (29.2%) or diet soft drinks only
      (20.9%), compared with males (21.7% and 14.0%, respectively) (P < .05). The
      youngest (16-24 years) consumers of sugar-sweetened soft drinks consumed twice
      (median, 3 cups/wk) as much as the eldest (55-65 years) (1.5 cups/wk) (P < .05).
      Respondents classified as overweight or obese were 1.7 times more likely to drink
      both sugar-sweetened and diet soft drinks compared with other respondents (P =
      .02). CONCLUSIONS AND IMPLICATIONS: This study identified a high prevalence of
      soft drink consumption within the population (74.5%). These results identify
      young people (16-24 years of age), as well as males, as population groups to
      target through public health interventions to reduce soft drink consumption.

PMID- 23877055
TI  - The development and evaluation of an Internet-based intervention to increase
      awareness about food portion sizes: a randomized, controlled trial.
AB  - OBJECTIVE: To develop a Web-based tool (PortionSize@warenessTool) and to evaluate
      its effectiveness in increasing awareness of reference serving sizes and factors
      that may contribute to overeating in response to large portion sizes. METHODS: A
      randomized, controlled trial (intervention, n = 167; control, n = 143) was
      conducted. The authors measured awareness of reference serving size and
      overeating triggers from larger portions by an online questionnaire, assessed at
      baseline and 1 week later. Exposure dose reflected online activity (eg, number of
      Web pages viewed). Process evaluation data were collected within the intervention
      group. RESULTS: The intervention group demonstrated significantly higher
      awareness of reference serving sizes (eta(2) = .062; P < .001) and overeating
      triggers from larger portions (eta(2) = .061; P < .001) at posttest. Also, the
      authors observed a dose-dependent effect that led to improved awareness.
      CONCLUSIONS AND IMPLICATIONS: The PortionSize@warenessTool constitutes a
      promising tool to improve portion size awareness.

PMID- 23877056
TI  - Low bone mineral density is associated with dyslipidemia in South Korean men: the
      2008-2010 Korean National Health and Nutrition Examination Survey.
AB  - This study examined the relationship between bone mineral density (BMD) and
      dyslipidemia in South Korean men. Data from 6,300 men who participated in the
      Korean National Health and Nutrition Examination Survey from 2008 to 2010 were
      analyzed, including serum levels of total cholesterol (TC), high-density
      lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and
      triglyceride (TG) after 8 hours of fasting and mean BMD measured at the lumbar
      spine (LS), total hip (TH), and femoral neck (FN). Dyslipidemia was defined
      according to the criteria of the National Cholesterol Education Program Adult
      Treatment Panel III. Other parameters of dyslipidemia were also calculated, such
      as TG/HDL-C, TC/HDL-C, non-HDL-C (NHDL-C), and LDL-C/HDL-C. Men with dyslipidemia
      and high levels of TG, TG/HDL-C, TC/HDL-C, NHDL-C, and LDL-C/HDL-C had lower BMD
      than men without dyslipidemia at the LS, TH, and FN after adjustment for age and
      body mass index (all p<0.01). On multivariable regression analysis, all odds
      ratios for high levels of TG, TG/HDL-C, TC/HDL-C, NHDL-C, and LDL-C/HDL-C with an
      increase in BMD (per standard deviation) were <1 at all 3 sites after adjustment
      for age and body mass index (model 1). After adjustment for all covariates, only
      odds ratios for high levels of TG, TG/HDL-C, TC/HDL-C, and NHDL-C were <1 at all
      3 sites (model 2), but an increase in BMD was not associated with high LDL-C
      levels in models 1 and 2. In conclusion, BMD was inversely correlated with
      parameters of atherogenic dyslipidemia in South Korean men. 

PMID- 23877057
TI  - Correction of joint angles from Kinect for balance exercising and assessment.
AB  - The new generation of videogame interfaces such as Microsoft's Kinect opens the
      possibility of implementing exercise programs for physical training, and of
      evaluating and reducing the risks of elderly people falling. However,
      applications such as these might require measurements of joint kinematics that
      are more robust and accurate than the standard output given by the available
      middleware. This article presents a method based on particle filters for
      calculating joint angles from the positions of the anatomical points detected by
      PrimeSense's NITE software. The application of this method to the measurement of
      lower limb kinematics reduced the error by one order of magnitude, to less than
      10 degrees , except for hip axial rotation, and it was advantageous over inverse
      kinematic analysis, in ensuring a robust and smooth solution without
      singularities, when the limbs are out-stretched and anatomical landmarks are
      aligned. 

PMID- 23877058
TI  - UV-B radiation induces Mu element somatic transposition in maize.

PMID- 23877059
TI  - Frequency and characteristics of isolated psychiatric episodes in anti-N-methyl-d
      aspartate receptor encephalitis.
AB  - IMPORTANCE: Patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis
      often develop prominent psychiatric manifestations. The frequency and type of
      isolated psychiatric episodes (pure psychiatric symptoms without neurological
      involvement) either as initial presentation of the disease or as relapse are
      unknown. OBJECTIVE: To determine the frequency, symptoms, and outcome of isolated
      psychiatric episodes in a cohort of patients with anti-NMDAR encephalitis.
      DESIGN, SETTING, AND PARTICIPANTS: Observational cohort of patients diagnosed
      during a5-year period (median follow-up, 2 years). A total of 571 patients with
      IgG antibodies against the NR1 subunit of the NMDAR were included in the study.
      Antibody studies were performed at the University of Pennsylvania and the
      University of Barcelona, and clinical information was obtained by us or referring
      physicians. MAIN OUTCOMES AND MEASURES: Frequency, type of symptoms, and outcome
      of patients with anti-NMDAR encephalitis and isolated psychiatric manifestations.
      RESULTS: Of 571 patients, 23 (4%) developed isolated psychiatric episodes, 5 at
      disease onset and 18 during relapse. For all 23 patients, age (median, 20 years),
      sex (91%female), and tumor association (43%; ovarian teratoma in all cases) were
      similar to the population at large.Predominant symptoms included delusional
      thinking (74%), mood disturbances (70%,usually manic), and aggression (57%).
      Brain magnetic resonance imaging findings were abnormal in 10 of 22 patients
      (45%) and cerebrospinal fluid analysis showed pleocytosis in 17 of 22 patients
      (77%). Eighty-three percent of the patients had full or substantial recovery
      after immunotherapy and tumor resection when appropriate. After relapse, 17 of 18
      patients(94%) returned to a similar or better prerelapse functional level.
      CONCLUSIONS AND RELEVANCE: Isolated psychiatric episodes are rare but can occur
      as initial onset or relapse of anti-NMDAR encephalitis. Recognition of these
      episodes is important because they respond to immunotherapy. In patients with new
      onset psychosis, having a history of encephalitis, subtle neurological symptoms,
      and/or abnormal results on ancillary tests should prompt screening for NMDAR
      antibodies.

PMID- 23877060
TI  - Prospective study of breakfast eating and incident coronary heart disease in a
      cohort of male US health professionals.
AB  - BACKGROUND: Among adults, skipping meals is associated with excess body weight,
      hypertension, insulin resistance, and elevated fasting lipid concentrations.
      However, it remains unknown whether specific eating habits regardless of dietary
      composition influence coronary heart disease (CHD) risk. The objective of this
      study was to prospectively examine eating habits and risk of CHD. METHODS AND
      RESULTS: Eating habits, including breakfast eating, were assessed in 1992 in 26
      902 American men 45 to 82 years of age from the Health Professionals Follow-up
      Study who were free of cardiovascular disease and cancer. During 16 years of
      follow-up, 1527 incident CHD cases were diagnosed. Cox proportional hazards
      models were used to estimate relative risks and 95% confidence intervals for CHD,
      adjusted for demographic, diet, lifestyle, and other CHD risk factors. Men who
      skipped breakfast had a 27% higher risk of CHD compared with men who did not
      (relative risk, 1.27; 95% confidence interval, 1.06-1.53). Compared with men who
      did not eat late at night, those who ate late at night had a 55% higher CHD risk
      (relative risk, 1.55; 95% confidence interval, 1.05-2.29). These associations
      were mediated by body mass index, hypertension, hypercholesterolemia, and
      diabetes mellitus. No association was observed between eating frequency (times
      per day) and risk of CHD. CONCLUSIONS: Eating breakfast was associated with
      significantly lower CHD risk in this cohort of male health professionals.

PMID- 23877062
TI  - Obesity begets atrial fibrillation: a contemporary summary.

PMID- 23877063
TI  - Should off-pump coronary artery bypass grafting be abandoned?

PMID- 23877064
TI  - ECG response: July 23, 2013.

PMID- 23877061
TI  - Pathological ventricular remodeling: mechanisms: part 1 of 2.
AB  - Despite declines in heart failure morbidity and mortality with current therapies,
      rehospitalization rates remain distressingly high, substantially affecting
      individuals, society, and the economy. As a result, the need for new therapeutic
      advances and novel medical devices is urgent. Disease-related left ventricular
      remodeling is a complex process involving cardiac myocyte growth and death,
      vascular rarefaction, fibrosis, inflammation, and electrophysiological
      remodeling. Because these events are highly interrelated, targeting a single
      molecule or process may not be sufficient. Here, we review molecular and cellular
      mechanisms governing pathological ventricular remodeling. 

PMID- 23877065
TI  - Circumferential hyperechogenecity as an ultrasound sign of infected abdominal
      aortic aneurysm.

PMID- 23877066
TI  - Multiple thrombi in the ascending aorta: usefulness of contrast transesophageal
      echocardiography in a case of Horton's aortitis.

PMID- 23877068
TI  - Letter by Kagawa et al regarding article, "hypothermia in comatose survivors from
      out-of-hospital cardiac arrest: pilot trial comparing 2 levels of target
      temperature".

PMID- 23877070
TI  - Characterization of metabolites of 20(S)-protopanaxadiol in rats using ultra
      performance liquid chromatography/quadrupole-time-of-flight mass spectrometry.
AB  - In this study, ultra-performance liquid chromatography (UPLC)/quadrupole-time-of
      flight mass spectrometry (QTOF-MS) was applied to the rapid analysis of 20(S)
      protopanaxadiol (PPD) metabolites in rats after oral administration, enabling the
      structural characterization of 23 metabolites in plasma, bile, urine, and feces.
      16 of these, including M1-M5, M9, and M11-M15, have not been previously reported.
      The results also indicated that demethylation, dehydration, dehydrogenation,
      oxidation, deoxidation, and glucuronidation were the major metabolic reactions of
      PPD in vivo. This study provides important information about the metabolism of
      PPD which will be helpful for fully understanding its mechanism of action.
      Furthermore, structural modification of PPD in vivo may aid in obtaining new
      chemical derivatives for pharmacological screening. 

PMID- 23877069
TI  - Optical control of mammalian endogenous transcription and epigenetic states.
AB  - The dynamic nature of gene expression enables cellular programming, homeostasis
      and environmental adaptation in living systems. Dissection of causal gene
      functions in cellular and organismal processes therefore necessitates approaches
      that enable spatially and temporally precise modulation of gene expression.
      Recently, a variety of microbial and plant-derived light-sensitive proteins have
      been engineered as optogenetic actuators, enabling high-precision spatiotemporal
      control of many cellular functions. However, versatile and robust technologies
      that enable optical modulation of transcription in the mammalian endogenous
      genome remain elusive. Here we describe the development of light-inducible
      transcriptional effectors (LITEs), an optogenetic two-hybrid system integrating
      the customizable TALE DNA-binding domain with the light-sensitive cryptochrome 2
      protein and its interacting partner CIB1 from Arabidopsis thaliana. LITEs do not
      require additional exogenous chemical cofactors, are easily customized to target
      many endogenous genomic loci, and can be activated within minutes with
      reversibility. LITEs can be packaged into viral vectors and genetically targeted
      to probe specific cell populations. We have applied this system in primary mouse
      neurons, as well as in the brain of freely behaving mice in vivo to mediate
      reversible modulation of mammalian endogenous gene expression as well as targeted
      epigenetic chromatin modifications. The LITE system establishes a novel mode of
      optogenetic control of endogenous cellular processes and enables direct testing
      of the causal roles of genetic and epigenetic regulation in normal biological
      processes and disease states. 

PMID- 23877071
TI  - Maternal inflammation promotes fetal microglial activation and increased
      cholinergic expression in the fetal basal forebrain: role of interleukin-6.
AB  - BACKGROUND: Perinatal exposure to infectious agents with associated maternal
      immune activation (MIA) leads to neuroanatomical and behavioral dysregulation
      reminiscent of autism spectrum disorders. Persistent microglial activation as
      well as increased choline acetyltransferase (ChAT) activity in the basal
      forebrain (BF) are characteristic of autistic subjects. Previous studies have
      shown that medium from activated microglia promotes cholinergic differentiation
      of precursors in the BF. We sought to determine whether MIA in vivo would lead to
      a similar effect on developing BF neurons. METHODS: Pregnant mice were treated
      with the viral mimic polyinosinic-polycytidylic acid (poly(I:C)) or saline.
      RESULTS: Poly(I:C) treatment resulted in increased production of cytokines and
      chemokines in fetal microglia and increased ChAT activity and cholinergic cell
      number in the perinatal BF. Whether microglial activation causes these changes is
      unclear. Examination of fetal brains from mice lacking interleukin-6 (IL-6 KOs)
      revealed an elevation in non-microglial-derived cytokines and chemokines over
      wild-type controls. Moreover, IL-6 KO offspring showed an elevation of ChAT
      activity even in the absence of poly(I:C) administration. CONCLUSION: These data
      suggest that elevations in cytokines and/or chemokines caused either by maternal
      poly(I:C) administration or by the absence of IL-6 are associated with
      alterations in cholinergic development in the BF.

PMID- 23877073
TI  - Measuring femoral and rotational alignment: EOS system versus computed
      tomography.
AB  - INTRODUCTION: Computed tomography (CT) is currently the reference standard for
      measuring femoral and tibial rotational alignment. The EOS System is a new
      biplanar low-dose radiographic device that allows 3-dimensional lower-limb
      modelling with automated measurements of femoral and tibial rotational alignment
      (torsion). HYPOTHESIS: Femoral and tibial torsion measurements provided by the
      EOS System are equivalent to those obtained using CT. MATERIALS AND METHODS: In a
      retrospective analysis of 43 lower limbs in 30 patients, three senior
      radiologists measured femoral and tibial torsion on both CT and EOS images.
      Agreement between CT and EOS values was assessed by computing Pearson's
      correlation coefficient and interobserver reproducibility by computing the
      intraclass correlation coefficient (ICC). RESULTS: Femoral torsion was 13.4
      degrees  by EOS vs. 13.7 degrees  by CT (P=0.5) and tibial torsion was 30.8
      degrees  by EOS vs. 30.3 degrees  by CT (P=0.4). Strong associations were found
      between EOS and CT values for both femoral torsion (P=0.93) and tibial torsion
      (P=0.89). With EOS, the ICC was 0.93 for femoral torsion and 0.86 for tibial
      torsion; corresponding values with CT were 0.90 and 0.92. DISCUSSION: The EOS
      system is a valid alternative to CT for lower-limb torsion measurement. EOS
      imaging allows a comprehensive evaluation in all three planes while substantially
      decreasing patient radiation exposure. LEVEL OF EVIDENCE: Level III, case
      control.

PMID- 23877074
TI  - Flooding tolerance in interspecific introgression lines containing chromosome
      segments from teosinte (Zea nicaraguensis) in maize (Zea mays subsp. mays).
AB  - BACKGROUND AND AIMS: Nicaraguan teosinte (Zea nicaraguensis), a species found in
      frequently flooded areas, provides useful germplasm for breeding flooding
      tolerant maize (Z. mays subsp. mays). The objective of this study was to select
      flooding-tolerant lines using a library of introgression lines (ILs), each
      containing a chromosome segment from Z. nicaraguensis in the maize inbred line
      Mi29. METHODS: To produce the ILs, a single F1 plant derived from a cross between
      maize Mi29 and Z. nicaraguensis was backcrossed to Mi29 three times, self
      pollinated four times and genotyped using simple sequence repeat markers.
      Flooding tolerance was evaluated at the seedling stage under reducing soil
      conditions. KEY RESULTS: By backcrossing and selfing, a series of 45 ILs were
      developed covering nearly the entire maize genome. Five flooding-tolerant lines
      were identified from among the ILs by evaluating leaf injury. Among these, line
      IL#18, containing a Z. nicaraguensis chromosome segment on the long arm of
      chromosome 4, showed the greatest tolerance to flooding, suggesting the presence
      of a major quantitative trait locus (QTL) in that region. The presence of the QTL
      was verified by examining flooding tolerance in a population segregating for the
      candidate region of chromosome 4. There was no significant relationship between
      the capacity to form constitutive aerenchyma and flooding tolerance in the ILs,
      indicating the presence of other factors related to flooding tolerance under
      reducing soil conditions. CONCLUSIONS: A flooding-tolerant genotype, IL#18, was
      identified; this genotype should be useful for maize breeding. In addition,
      because the chromosome segments of Z. nicaraguensis in the ILs cover nearly the
      entire genome and Z. nicaraguensis possesses several unique traits related to
      flooding tolerance, the ILs should be valuable material for additional QTL
      detection and the development of flooding-tolerant maize lines.

PMID- 23877075
TI  - Programmed cell death promotes male sterility in the functional dioecious Opuntia
      stenopetala (Cactaceae).
AB  - BACKGROUND AND AIMS: The sexual separation in dioecious species has interested
      biologists for decades; however, the cellular mechanism leading to unisexuality
      has been poorly understood. In this study, the cellular changes that lead to male
      sterility in the functionally dioecious cactus, Opuntia stenopetala, are
      described. METHODS: The spatial and temporal patterns of programmed cell death
      (PCD) were determined in the anthers of male and female flowers using scanning
      electron microscopy analysis and histological observations, focusing attention on
      the transition from bisexual to unisexual development. In addition, terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling assays were used as
      an indicator of DNA fragmentation to corroborate PCD. KEY RESULTS: PCD was
      detected in anthers of both female and male flowers, but their patterns differed
      in time and space. Functionally male individuals developed viable pollen, and
      normal development involved PCD on each layer of the anther wall, which occurred
      progressively from the inner (tapetum) to the outer layer (epidermis).
      Conversely, functional female individuals aborted anthers by premature and
      displaced PCD. In anthers of female flowers, the first signs of PCD, such as a
      nucleus with irregular shape, fragmented and condensed chromatin, high
      vacuolization and condensed cytoplasm, occurred at the microspore mother cell
      stage. Later these features were observed simultaneously in all anther wall
      layers, connective tissue and filament. Neither pollen formation nor anther
      dehiscence was detected in female flowers of O. stenopetala due to total anther
      disruption. CONCLUSIONS: Temporal and spatial changes in the patterns of PCD are
      responsible for male sterility of female flowers in O. stenopetala. Male
      fertility requires the co-ordination of different events, which, when altered,
      can lead to male sterility and to functionally unisexual individuals. PCD could
      be a widespread mechanism in the determination of functionally dioecious species.

PMID- 23877076
TI  - Population structure of Cynara cardunculus complex and the origin of the
      conspecific crops artichoke and cardoon.
AB  - BACKGROUND AND AIMS: Globe artichoke and leafy cardoon, two crops within the same
      species Cynara cardunculus, are traditionally cultivated in the Mediterranean
      region and play a significant role in the agricultural economy of this area. The
      two cultigens have different reproductive systems: artichoke is generally
      vegetatively propagated, while leafy cardoon is seed propagated. The
      domestication events underlying the origin of both artichoke and cultivated
      cardoon from their wild relative and the area of occurrence are not yet fully
      understood. The aim of this study was to investigate population structure in wild
      cardoon, globe artichoke and leafy cardoon material and infer domestication
      events. METHODS: Thirty-five microsatellite (simple sequence repeat) markers,
      distributed in the C. cardunculus genome, and a large geographical and numerical
      sampling in southern Europe and North Africa were used to assess population
      structure and diversity. KEY RESULTS: The results suggest the presence of two
      distinct domestication events for artichoke and leafy cardoon, and also suggest a
      new possible scenario, with western wild cardoon having originated from
      cultivated cardoon escaped from cultivation. Evidence was found for a demographic
      bottleneck in the past history of globe artichoke. CONCLUSIONS: The results shed
      new light on the relationships between the three taxa of C. cardunculus and
      highlight relevant aspects on the evolution of domestication of two crops with a
      different reproductive system within the same species. It is proposed that the
      probable centre of origin of artichoke is located in southern Italy, probably
      Sicily.

PMID- 23877080
TI  - Failure of an Internet-based health care intervention for colonoscopy
      preparation: a caveat for investigators.

PMID- 23877079
TI  - Statins and musculoskeletal conditions, arthropathies, and injuries.
AB  - IMPORTANCE: Statin use may be associated with increased musculoskeletal adverse
      events, especially in physically active individuals. OBJECTIVE: To determine
      whether statin use is associated with musculoskeletal conditions, including
      arthropathy and injury, in a military health care system. DESIGN: A retrospective
      cohort study with propensity score matching. SETTING: San Antonio Military Multi
      Market. PARTICIPANTS: Tricare Prime/Plus beneficiaries evaluated from October 1,
      2003, to March 1, 2010. INTERVENTIONS: Statin use during fiscal year 2005. On the
      basis of medication fills, patients were divided into 2 groups: statin users
      (received a statin for at least 90 days) and nonusers (never received a statin
      throughout the study period). MAIN OUTCOMES AND MEASURES: Using patients'
      baseline characteristics, we generated a propensity score that was used to match
      statin users and nonusers; odds ratios (ORs) were determined for each outcome
      measure. Secondary analyses determined adjusted ORs for all patients who met
      study criteria and a subgroup of patients with no comorbidities identified using
      the Charlson Comorbidity Index. Sensitivity analysis further determined adjusted
      ORs for a subgroup of patients with no musculoskeletal diseases at baseline and a
      subgroup of patients who continued statin therapy for 2 years or more. The
      occurrence of musculoskeletal conditions was determined using prespecified groups
      of International Classification of Diseases, Ninth Revision, ClinicalModification
      codes: Msk1, all musculoskeletal diseases; Msk1a, arthropathies and related
      diseases; Msk1b, injury-related diseases (dislocation, sprain, strain); and Msk2,
      drug-associated musculoskeletal pain. RESULTS: A total of 46 249 individuals met
      study criteria (13 626 statin users and 32 623 nonusers). Of these, we propensity
      score-matched 6967 statin users with 6967 nonusers. Among matched pairs, statin
      users had a higher OR for Msk1 (OR, 1.19; 95% CI, 1.08-1.30), Msk1b (1.13; 1.05
      1.21), and Msk2 (1.09; 1.02-1.18); the OR for Msk1a was 1.07 (0.99-1.16; P =
      .07). Secondary and sensitivity analyses revealed higher adjusted ORs for statin
      users in all outcome groups. CONCLUSIONS AND RELEVANCE: Musculoskeletal
      conditions, arthropathies, injuries, and pain are more common among statin users
      than among similar nonusers. The full spectrum of statins' musculoskeletal
      adverse events may not be fully explored, and further studies are warranted,
      especially in physically active individuals.

PMID- 23877081
TI  - Management of antimicrobial allergies by infectious diseases physicians.

PMID- 23877082
TI  - Patient education: one size does not fit all.

PMID- 23877083
TI  - Sources of discomfort in persons with dementia.

PMID- 23877084
TI  - Ascorbic acid supplements and kidney stone risk.

PMID- 23877086
TI  - Identification of microRNAs in blood and urine as tumour markers for the
      detection of urinary bladder cancer.
AB  - Since differential expression of microRNAs (miRNAs) has been found to be highly
      associated with several types of cancer, the goal of the present study was to
      identify an miRNA fingerprint as a non-invasive diagnostic tool to detect urinary
      bladder cancer using the easily accessible samples of whole blood and urine.
      Blood and urine samples from 4 controls and from patients suffering from
      superficial and invasive bladder cancer were analyzed using miRNA microarray
      consisting of 754 human miRNAs from the Sanger database v14. Using RT-qPCR
      technique, 6 of the differentially expressed miRNAs were validated in the
      controls (20 blood, 19 urine samples) and patients with superficial (18 blood, 16
      urine samples) or invasive (20 blood and urine samples each) tumours. Three blood
      miRNAs (miR-26b-5p, miR-144-5p, miR-374-5p) were found to be significantly
      upregulated in invasive bladder tumour patients (P<0.05) when compared to the
      control group. The expression of 2 miRNAs (miR-618, miR-1255b-5p) in the urine of
      patients with invasive tumours was significantly (P<0.05) increased in comparison
      to the control group. Blood miR-26b-5p detected the presence of invasive bladder
      tumours with 94% specificity and 65% sensitivity. The urine miR-1255b-5p reached
      68% specificity and 85% sensitivity in the diagnosis of invasive tumours. This
      pilot study represents the first characterization of an miRNA profile for urinary
      bladder tumours in whole blood samples. In addition, it was shown that invasive
      bladder tumours could be identified by differentially expressed urine miRNAs.
      Further studies are needed to test the clinical usefulness for bladder cancer
      detection and surveillance.

PMID- 23877085
TI  - Ascorbic acid supplements and kidney stone risk--reply.

PMID- 23877087
TI  - Common features of low-temperature spin-charge separation and superlattice
      formation in multiferroic manganites and antiferromagnetic cuprates.
AB  - The paper reports on new results obtained for tetragonal quasi-2D
      antiferromagnetic Eu2CuO4 at temperatures below 30-40 K. A set of ferromagnetic
      resonance lines similar to ones obtained earlier for a number of multiferroic
      manganites (Sanina et al 2012 J. Phys.: Condens. Matter 24 346002), with similar
      electric polarization and local conductivity, were measured, i.e., a multiferroic
      behavior was revealed in Eu2CuO4 at low temperatures. We attribute these
      observations to the 1D superlattices that are formed due to phase separation and
      self-organization of charge carriers and occupy a small crystal volume, as in the
      multiferroic manganites studied earlier. Characteristic features of these
      superlattices include a spin-charge separation and conductivity in their
      ferromagnetic layers. It is supposed that superlattices are domain walls
      separating the volume antiferromagnetic domains. A similarity between the
      superlattices in a number of crystals having different symmetries and bulk
      properties suggests that a topological order similar to that of the topological
      insulator exists in them at low temperatures. 

PMID- 23877088
TI  - The sphere-to-rod transition of squaraine-embedded micelles: a self-assembly
      platform displays a distinct response to cysteine and homocysteine.
AB  - A simple self-assembly platform based on squaraine-embedded CTAB micelles can
      readily discriminate between Cys and Hcy with different absorption and
      fluorescence signals. The recognition mechanism is attributed to the fact that
      analyte adducts trigger the CTAB micelles to undergo sphere-to-rod transition. 

PMID- 23877089
TI  - Comparison of a full food-frequency questionnaire with the three-day unweighted
      food records in young Polish adult women: implications for dietary assessment.
AB  - The food frequency questionnaire (FFQ) and the food record (FR) are among the
      most common methods used in dietary research. It is important to know that is it
      possible to use both methods simultaneously in dietary assessment and prepare a
      single, comprehensive interpretation. The aim of this study was to compare the
      energy and nutritional value of diets, determined by the FFQ and by the three-day
      food records of young women. The study involved 84 female students aged 21-26
      years (mean of 22.2 +/- 0.8 years). Completing the FFQ was preceded by obtaining
      unweighted food records covering three consecutive days. Energy and nutritional
      value of diets was assessed for both methods (FFQ-crude, FR-crude). Data obtained
      for FFQ-crude were adjusted with beta-coefficient equaling 0.5915 (FFQ-adjusted)
      and regression analysis (FFQ-regressive). The FFQ-adjusted was calculated as FR
      crude/FFQ-crude ratio of mean daily energy intake. FFQ-regressive was calculated
      for energy and each nutrient separately using regression equation, including FFQ
      crude and FR-crude as covariates. For FR-crude and FFQ-crude the energy value of
      diets was standardized to 2000 kcal (FR-standardized, FFQ-standardized). Methods
      of statistical comparison included a dependent samples t-test, a chi-square test,
      and the Bland-Altman method. The mean energy intake in FFQ-crude was
      significantly higher than FR-crude (2740.5 kcal vs. 1621.0 kcal, respectively).
      For FR-standardized and FFQ-standardized, significance differences were found in
      the mean intake of 18 out of 31 nutrients, for FR-crude and FFQ-adjusted in 13
      out of 31 nutrients and FR-crude and FFQ-regressive in 11 out of 31 nutrients.
      The Bland-Altman method showed an overestimation of energy and nutrient intake by
      FFQ-crude in comparison to FR-crude, e.g., total protein was overestimated by
      34.7 g/day (95% Confidence Interval, CI: -29.6, 99.0 g/day) and fat by 48.6 g/day
      (95% CI: -36.4, 133.6 g/day). After regressive transformation of FFQ, the
      absolute difference between FFQ-regressive and FR-crude equaled 0.0 g/day and 95%
      CI were much better (e.g., for total protein 95% CI: -32.7, 32.7 g/day, for fat
      95% CI: -49.6, 49.6 g/day). In conclusion, differences in nutritional value of
      diets resulted from overestimating energy intake by the FFQ in comparison to the
      three-day unweighted food records. Adjustment of energy and nutrient intake
      applied for the FFQ using various methods, particularly regression equations,
      significantly improved the agreement between results obtained by both methods and
      dietary assessment. To obtain the most accurate results in future studies using
      this FFQ, energy and nutrient intake should be adjusted by the regression
      equations presented in this paper. 

PMID- 23877090
TI  - The relationship of docosahexaenoic acid (DHA) with learning and behavior in
      healthy children: a review.
AB  - Childhood is a period of brain growth and maturation. The long chain omega-3
      fatty acid, docosahexaenoic acid (DHA), is a major lipid in the brain recognized
      as essential for normal brain function. In animals, low brain DHA results in
      impaired learning and behavior. In infants, DHA is important for optimal visual
      and cognitive development. The usual intake of DHA among toddlers and children is
      low and some studies show improvements in cognition and behavior as the result of
      supplementation with polyunsaturated fatty acids including DHA. The purpose of
      this review was to identify and evaluate current knowledge regarding the
      relationship of DHA with measures of learning and behavior in healthy school-age
      children. A systematic search of the literature identified 15 relevant
      publications for review. The search found studies which were diverse in purpose
      and design and without consistent conclusions regarding the treatment effect of
      DHA intake or biomarker status on specific cognitive tests. However, studies of
      brain activity reported benefits of DHA supplementation and over half of the
      studies reported a favorable role for DHA or long chain omega-3 fatty acids in at
      least one area of cognition or behavior. Studies also suggested an important role
      for DHA in school performance. 

PMID- 23877092
TI  - Diverse accumulation and distribution of nutrient elements in developing wheat
      grain studied by laser ablation inductively coupled plasma mass spectrometry
      imaging.
AB  - The present study focused on the elemental distribution in the developing wheat
      grain by using the laser ablation inductively coupled plasma mass spectrometry
      (LA-ICP-MS) imaging technique. Our studies show that the embryo accumulated high
      concentrations of nutrient elements, such as Fe, K, Cu, and Zn, while Ca was
      accumulated in the bran of the wheat grain which might be attributed to its
      function of structural maintenance. In the endosperm the majority of the
      nutrients were located in the aleurone layer. Within the grain, the embryo could
      be considered as a nutrient pool for macro- and micro-elements essential for the
      development of the seedling. Elemental images showed that considerable amounts of
      nutrients were stored in the scutellum of the embryo, which might be related to
      the high gene expression of element transporters in the scutellum. Root primordia
      and leaf primordia were enriched in particular elements, such as Mn and Zn
      respectively. In total 34 cross sections were analyzed and used for generation of
      a sequence of elemental distribution images to demonstrate elemental changes
      along the perpendicular axis of the wheat grain embryo. Further development of
      three-dimensional modeling will be combined with physiological studies to better
      understand the mechanisms of elemental distribution and storage in the wheat
      grain. These studies will provide fundamental knowledge on improving the
      nutritional value and agronomic practices. 

PMID- 23877093
TI  - Uranyl-halide complexation in N,N-dimethylformamide: halide coordination trend
      manifests hardness of [UO2]2+.
AB  - Complexation of [UO2](2+) with Cl(-), Br(-), and I(-) in N,N-dimethylformamide
      (DMF) was studied by UV-vis absorption spectroscopy and extended X-ray absorption
      fine structure (EXAFS) to clearly differentiate halide coordination strengths to
      [UO2](2+). In the Cl(-) system, it was clarified that the Cl(-) coordination to
      [UO2](2+) in DMF proceeds almost quantitatively. The coordination number of Cl(-)
      almost quantitatively increases up to 4, i.e., the limiting complex is [UO2Cl4](2
      ). Logarithmic gross stability constants of [UO2Cl(x)](2-x) (x = 1-4) were
      evaluated as log beta1 = 9.67, log beta2 = 15.49, log beta3 = 19.89, and log
      beta4 = 24.63 from UV-vis titration experiments. The EXAFS results well
      demonstrated not only the Cl(-) coordination, but also the DMF solvation in the
      equatorial plane of [UO2](2+). The interaction of Br(-) and I(-) with [UO2](2+)
      in DMF was also investigated. As a result, the Br(-) coordination to [UO2](2+)
      stops at the second step, i.e., only [UO2Br](+) and UO2Br2 were observed. The
      molecular structure of each occurring species was confirmed by EXAFS. The
      evaluated log betax values of [UO2Br(x)](2-x) (x = 1, 2) are 3.45 and 5.42,
      respectively. The much smaller log betax than those of [UO2Cl(x)](2-x) indicates
      that Br(-) is a much weaker ligand to [UO2](2+) than Cl(-). The EXAFS experiments
      revealed that the presence of I(-) in the test solution does not modify any
      coordination structure around [UO2](2+). Thus, I(-) does not form any stable
      [UO2](2+) complexes in DMF. Consequently, the stability of the halido complexes
      of [UO2](2+) in DMF is exactly in line with the hardness order of halides.

PMID- 23877091
TI  - Peculiarities of one-carbon metabolism in the strict carnivorous cat and the role
      in feline hepatic lipidosis.
AB  - Research in various species has indicated that diets deficient in labile methyl
      groups (methionine, choline, betaine, folate) produce fatty liver and links to
      steatosis and metabolic syndrome, but also provides evidence of the importance of
      labile methyl group balance to maintain normal liver function. Cats, being
      obligate carnivores, rely on nutrients in animal tissues and have, due to
      evolutionary pressure, developed several physiological and metabolic adaptations,
      including a number of peculiarities in protein and fat metabolism. This has led
      to specific and unique nutritional requirements. Adult cats require more dietary
      protein than omnivorous species, maintain a consistently high rate of protein
      oxidation and gluconeogenesis and are unable to adapt to reduced protein intake.
      Furthermore, cats have a higher requirement for essential amino acids and
      essential fatty acids. Hastened use coupled with an inability to conserve certain
      amino acids, including methionine, cysteine, taurine and arginine, necessitates a
      higher dietary intake for cats compared to most other species. Cats also
      seemingly require higher amounts of several B-vitamins compared to other species
      and are predisposed to depletion during prolonged inappetance. This carnivorous
      uniqueness makes cats more susceptible to hepatic lipidosis. 

PMID- 23877094
TI  - Making vaccines "on demand": a potential solution for emerging pathogens and
      biodefense?
AB  - The integrated US Public Health Emergency Medical Countermeasures Enterprise
      (PHEMCE) has made great strides in strategic preparedness and response
      capabilities. There have been numerous advances in planning, biothreat
      countermeasure development, licensure, manufacturing, stockpiling and deployment.
      Increased biodefense surveillance capability has dramatically improved, while new
      tools and increased awareness have fostered rapid identification of new potential
      public health pathogens. Unfortunately, structural delays in vaccine design,
      development, manufacture, clinical testing and licensure processes remain
      significant obstacles to an effective national biodefense rapid response
      capability. This is particularly true for the very real threat of "novel
      pathogens" such as the avian-origin influenzas H7N9 and H5N1, and new
      coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development,
      production, clinical testing and licensure are incompatible with the prompt
      deployment needed for an effective public health response. An alternative
      approach, proposed here, is to apply computational vaccine design tools and rapid
      production technologies that now make it possible to engineer vaccines for novel
      emerging pathogen and WMD biowarfare agent countermeasures in record time. These
      new tools have the potential to significantly reduce the time needed to design
      string-of-epitope vaccines for previously unknown pathogens. The design process
      from genome to gene sequence, ready to insert in a DNA plasmid-can now be
      accomplished in less than 24 h. While these vaccines are by no means "standard,"
      the need for innovation in the vaccine design and production process is great.
      Should such vaccines be developed, their 60-d start-to-finish timeline would
      represent a 2-fold faster response than the current standard. 

PMID- 23877096
TI  - [Global health and the burden of chronic non-communicable diseases].

PMID- 23877095
TI  - Make caffeine visible: a fluorescent caffeine "traffic light" detector.
AB  - Caffeine has attracted abundant attention due to its extensive existence in
      beverages and medicines. However, to detect it sensitively and conveniently
      remains a challenge, especially in resource-limited regions. Here we report a
      novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which
      exhibits 250-fold fluorescence enhancement upon caffeine activation and high
      selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform
      infrared spectroscopy indicate that pi-stacking and hydrogen-bonding contribute
      to their interactions while dynamic light scattering and transmission electron
      microscopy experiments demonstrate the change of Caffeine Orange ambient
      environment induces its fluorescence emission. To utilize this probe in real
      life, we developed a non-toxic caffeine detection kit and tested it for caffeine
      quantification in various beverages. Naked-eye sensing of various caffeine
      concentrations was possible based on color changes upon irradiation with a laser
      pointer. Lastly, we performed the whole system on a microfluidic device to make
      caffeine detection quick, sensitive and automated. 

PMID- 23877097
TI  - [Nodular skin lesions in a patient with rheumatoid arthritis under therapy with
      anti-tumor necrosis factor-alpha].

PMID- 23877098
TI  - [Severe corneal infection by Colletotrichum gloeosporioides in a farmer].

PMID- 23877099
TI  - [Renal sympathetic denervation in resistant hypertension].

PMID- 23877100
TI  - [Reply].

PMID- 23877101
TI  - Cation size effects in mixed-ion metaphosphate glasses: structural
      characterization by multinuclear solid state NMR spectroscopy.
AB  - Metaphosphate glasses with two monovalent species A(1-x)B(x)PO3 (0 <=x<= 1) show
      mixed-ion effects (MIE) in the dc conductivities and glass transition
      temperatures, which are strongly dependent on the cation size mismatch between
      the two mobile species. In the present contribution, mixed-ion metaphosphate
      glasses based on the cation combinations Cs-Li, Rb-Li, and Cs-Ag, exhibiting
      particularly large size mismatches, are analyzed by (31)P, (87)Rb, (109)Ag and
      (133)Cs NMR to determine possible correlations between this mismatch and some of
      the structural properties critical to the development of the MIE: the local
      environments around the mobile species and their spatial distribution relative to
      each other. The results are compared with those obtained in the Na-Ag
      metaphosphate series, which serves as a reference system, with minimized cation
      mismatch MIE. The local coordination environments of the Ag(+), Rb(+) and Cs(+)
      ions follow analogous compositional trends as previously observed in Na-based
      mixed-ion metaphosphate glasses: for a given cation species A, the average A-O
      distance shows an expansion/compression when this cation is replaced by a second
      species B with smaller/bigger ionic radius, respectively. This compositional
      differentiation of the structural sites for the mobile species may contribute to
      the MIE. Concerning the relative spatial distribution of the mobile ions, results
      from (7)Li-(133)Cs (SEDOR) experiments indicate a random mixture of Cs and Li in
      Cs-Li metaphosphate glasses. While this result is in agreement with one of the
      fundamental hypotheses of the models proposed to describe the MIE, it is at
      variance with the observation of various partial cation segregation phenomena
      observed in Na-based mixed alkali glasses. This result suggests that cation size
      mismatch is not the decisive parameter in determining segregation or non
      statistical mixing of cations in the glass. In the Cs-Ag and Na-Ag glasses,
      (109)Ag spin-echo NMR reveals a progressive slowing down of the Ag(+) diffusion
      dynamics as this species is replaced by Cs(+) or Na(+). The substitution by the
      bigger Cs(+) ion causes a strong reduction in Ag(+) mobility suggesting the
      existence of separated diffusion pathways for these cations. In contrast,
      substitution by the similarly-sized Na(+) causes a much weaker mobility reduction
      consistent with the existence of Ag-Na cooperative hopping.

PMID- 23877102
TI  - Identification of the tri-Al tricitrate complex in Plantago almogravensis by
      hydrophilic interaction LC with parallel ICP-MS and electrospray Orbitrap MS/MS
      detection.
AB  - The identification of the ligands binding Al is essential to understand the
      mechanisms by which plants detoxify Al internally. However, studies concerning
      the speciation of Al have been frustrated by its complex chemistry. This work
      describes the identification of the tri-Al tricitrate (Al3cit3) complex in
      Plantago almogravensis, encompassing an integrated mass spectrometry approach
      based on hydrophilic interaction liquid chromatography (HILIC) and parallel
      detection by ICP-MS and ESI-MS/MS. This work also reports that both Al and Fe are
      bound by tricitrate, sometimes simultaneously, and the consequences of this
      finding are discussed. Of the complexes separated by size exclusion
      chromatography, Al3cit3 is the most stable occurring in P. almogravensis as it
      was the only one recovered after HILIC. This approach provided new information on
      the mechanism of Al detoxification in P. almogravensis, namely that Al is bound
      by the organic acid citrate and that the relative concentration of the detected
      complexes is affected by the organ type and internal Al concentration, and has
      potential for studying the speciation of Al in less tolerant plants. 

PMID- 23877103
TI  - Epidermal growth factor-like domain 8 inhibits the survival and proliferation of
      mouse thymocytes.
AB  - Thymic epithelial cells (TECs) play a critical role in T-cell development through
      their intercellular interactions and by producing various soluble proteins, such
      as growth factors, cytokines and chemokines. In this study, we report a new role
      for epidermal growth factor-like domain 8 (EGFL8) in the regulation of the
      survival and proliferation of mouse thymocytes. Mouse recombinant EGFL8 (rEGFL8)
      protein was produced using an E. coli system and its biological role in mouse
      thymocytes was determined. The injection of rEGFL8 in mice in vivo resulted in a
      decrease in the weight of the thymus, as well as in the number of total
      thymocytes; rEGFL8 also inhibited thymocyte proliferation and induced thymocyte
      apoptosis. Furthermore, rEGFL8 suppressed the expression of the Notch downstream
      targets, Hes1 and Hey1, in mouse thymocytes and TECs, indicating that EGFL8
      negatively regulates the Notch signaling pathway in these cells. The
      identification of the role of EGFL8 in thymocytes may aid in the determination of
      the fate of thymocytes during T-cell development.

PMID- 23877104
TI  - Functional expression of organic cation/carnitine transporter 2 (OCTN2/SLC22A5)
      in human brain capillary endothelial cell line hCMEC/D3, a human blood-brain
      barrier model.
AB  - The aim of this study was to examine whether organic cation/carnitine
      transporter 2 (OCTN2/SLC22A5) plays a role in the human blood-brain barrier (BBB)
      by evaluating its functional activity in human brain endothelial cells
      (hCMEC/D3), which are considered to be a model of the BBB. The uptake of [(3)H]L
      carnitine by hCMEC/D3 cells was time-, extracellular sodium- and concentration
      dependent, with a Km value of 15.7 uM. These results are consistent with the
      properties of OCTN2-mediated L-carnitine transport. hCMEC/D3 cells showed
      relatively high expression of OCTN2 mRNA, and this expression was effectively
      decreased at 24-72 h after lipofection of cells with OCTN2 siRNA under optimized
      conditions. [(3)H]L-Carnitine uptake was dramatically suppressed by silencing of
      the OCTN2 gene. The inhibitory effect of OCTN2 gene silencing was similar to that
      of an excess amount of unlabeled L-carnitine. These results indicate that OCTN2
      is involved in L-carnitine transport at the human BBB. 

PMID- 23877105
TI  - More relevant prediction for in vivo drug interaction of candesartan cilexetil on
      hepatic bile acid transporter BSEP using sandwich-cultured hepatocytes.
AB  - Bile salt export pump (BSEP) plays a major role in biliary secretion of bile
      salts; therefore, drug-induced cholestasis could occur because of BSEP inhibition
      by drugs. Drug interaction on hepatic bile canalicular transporters such as BSEP
      with prodrugs that are rapidly metabolized has not been evaluated well. In the
      present study, candesartan cilexetil (CIL) was used as a model compound and its
      inhibitory potential against BSEP was determined in sandwich-cultured human
      hepatocytes (hSCH) as well as in BSEP-expressing membrane vesicles. CIL exhibited
      potent BSEP inhibition with an IC50 value of 6.2 uM in the transport assay using
      membrane vesicles. In contrast, BSEP inhibition by CIL was not observed in hSCH
      after 120 min exposure. This discordance is possibly explained by metabolic
      elimination of CIL in hSCH because BSEP inhibition became reversely pronounced
      under the conditions where CIL metabolism was suppressed by diisopropyl
      fluorophosphates. The results observed in hSCH are consistent with the fact that
      liver dysfunction or jaundice occurs with low frequency in clinical use of CIL,
      which may not be obtained by membrane vesicle study on the effect of CIL on BSEP.

PMID- 23877106
TI  - Development of an integrated population pharmacokinetic model for oral
      levetiracetam in populations of various ages and ethnicities.
AB  - Levetiracetam [E Keppra((r))] is a second generation antiepileptic drug for
      different types of epilepsy in adults and children >=1 month. The objective is to
      develop a population pharmacokinetic model to describe the pharmacokinetics of
      levetiracetam in Japanese children and adults as well as North American children,
      the purpose being to explore potential dosing recommendations in Japanese
      children. Levetiracetam plasma concentration-time data were obtained from
      Japanese adult and pediatric clinical studies. The data were analyzed through non
      linear mixed effects modelling. The model was used to perform simulations and
      compare the exposure in Japanese children and adults. It was subsequently
      extended to North American children through an external validation. A one
      compartment model with first-order absorption and first-order elimination
      adequately described the data. The exposure parameters determined based on the
      simulations in children were well within the adult range. The external validation
      against historical data from North American children was successful. The
      integrated population pharmacokinetic model provided a good description of the
      data, confirming the similarity of levetiracetam pharmacokinetics in these
      various populations. In Japanese children, a target dose of 10 to 30 mg/kg twice
      daily ensures the same exposure as the recommended dose in Japanese adults of 500
      to 1,500 mg twice daily. 

PMID- 23877107
TI  - Genetic variations in UDP-glucuronosyltransferase 2B15 in a Korean population.
AB  - UDP-glucuronosyltransferase 2B15 (UGT2B15) is involved in the glucoronidation
      of steroid hormones as well as many drugs. Genetic variations in UGT2B15 have
      been shown to affect enzyme function and suggested to have a role in human
      diseases, such as breast and prostate cancers. In the present study, we sequenced
      genomic DNA from 50 normal Korean subjects to identify single nucleotide
      polymorphisms (SNPs) in UGT2B15. A total of thirteen genetic variations were
      found: two in exons, two in introns, seven in the 5'-untranslated region (UTR),
      and two in the 3'-UTR. The order and frequency distribution of UGT2B15 variations
      was: -1139T>C (rs9994887), -508G>A (rs1120265), -506T>A (rs1580083), 253T>G
      (rs1902023) (42%), 23687A>T (rs4148271) (31%), 2635A>T (rs2045100) (28%), -497C>T
      (14%), -378C>T (14%), 23669C>T (12%), and 23476A>C (rs4148269) (11%), with other
      minor alleles with a frequency of <10%. Thirteen variations were used to
      characterize linkage disequilibrium structures at the UGT2B15 locus. Five tag
      SNPs were identified, and the observed allelic frequencies were compared to those
      of other ethnic populations. This information describing genetic polymorphisms in
      UGT2B15 could serve as an important resource for studying individual variations
      in drug and hormone metabolism in Korean as well as other ethnic populations. 

PMID- 23877108
TI  - Inducing alignment of cyclic peptide nanotubes through the use of structured
      ionic liquids.
AB  - We describe a convenient route to the alignment of cyclic peptide nanotubes
      (CPNs). The key lies in the use of nanostructured ionic liquids. An ionic liquid
      supported membrane with orientated domains is demonstrated, leading to aligned
      CPNs within a solid membrane. 

PMID- 23877109
TI  - Cervical arthroplasty with Discover prosthesis: clinical outcomes and analysis of
      factors that may influence postoperative range of motion.
AB  - PURPOSE: The aim of this current study was to analyze the clinical outcomes after
      Discover cervical disc replacement and its effects on maintaining cervical
      lordosis and range of motion (ROM). The possible factors influencing
      postoperative ROM were analyzed. METHOD: 27 men and 28 women with a mean age of
      46.4 +/- 8.7 years were prospectively followed up for 2 years. Clinical outcomes
      were assessed using Japanese Orthopedic Association (JOA), Neck Disability Index
      (NDI), visual analog scale (VAS) and Odom's criteria. Radiographic information
      including segment and overall alignment, functional spinal unit (FSU) and overall
      ROM, and disc heights were prospectively collected during the follow-up. The
      correlations between the postoperative FSU ROM at last follow-up and influencing
      factors were analyzed. RESULTS: Mean NDI, JOA and VAS scores showed statistical
      improvements at last follow-up. Anterior migration of the prosthesis was detected
      in six cases. Heterotopic ossification was observed in ten patients. Mean FSU
      angle, endplate angle of the treated level and mean overall cervical alignment
      were all improved significantly at last follow-up (P < 0.001). However, mean FSU
      ROM of the treated segment significantly decreased postoperatively (P = 0.008),
      while mean overall ROM showed no significant differences. A significant
      correlation was found between preoperative FSU ROM and postoperative FSU ROM by
      the Pearson correlation coefficient (r = 0.325, P = 0.034). Multiple linear
      regression analysis confirmed that preoperative FSU ROM contributed independently
      to a model with a coefficient of determination of 0.37 (P = 0.034). CONCLUSIONS:
      In the 2 years follow-up, the Discover cervical disc arthroplasty has provided
      satisfactory clinical outcomes. It was able to substantially restore segment and
      overall cervical alignment while partially maintaining segment and overall
      cervical ROM. Additionally, we found that postoperative FSU ROM positively
      correlated with preoperative FSU ROM.

PMID- 23877110
TI  - Ultrasound-guided versus computed tomography-controlled periradicular injections
      in the middle and lower cervical spine: a prospective randomized clinical trial.
AB  - PURPOSE: We conducted this study to evaluate accuracy, time saving, radiation
      doses, safety, and pain relief of ultrasound (US)-guided periradicular injections
      versus computed tomography (CT)-controlled interventions in the cervical spine in
      a prospective randomized clinical trial. METHODS: Forty adult patients were
      consecutively enrolled and randomly assigned to either a US or a CT group. US
      guided periradicular injections were performed on a standard ultrasound device
      using a broadband linear array transducer. By basically following the osseous
      landmarks for level definition in "in-plane techniques", a spinal needle was
      advanced as near as possible to the intended, US-depicted nerve root. The
      respective needle tip positioning was then verified by CT. The control group
      underwent CT-guided injections, which were performed under standardized
      procedures using the CT-positioning laser function. RESULTS: The accuracy of US
      guided interventions was 100%. The mean time to final needle placement in the US
      group was 02:21 +/- 01:43 min:s versus 10:33 +/- 02:30 min:s in the CT group. The
      mean dose-length product radiation dose, including CT confirmation for study
      purposes only, was 25.1 +/- 16.8 mGy cm for the US group and 132.5 +/- 78.4 mGy
      cm for the CT group. Both groups showed the same significant visual analog scale
      decay (p < 0.05) without "inter-methodic" differences of pain relief (p > 0.05).
      CONCLUSIONS: US-guided periradicular injections are accurate, result in a
      significant reduction of procedure expenditure under the avoidance of radiation
      and show the same therapeutic effect as CT-guided periradicular injections.

PMID- 23877111
TI  - A semi-automated vascular access system for preclinical models.
AB  - Murine models are used extensively in biological and translational research. For
      many of these studies it is necessary to access the vasculature for the injection
      of biologically active agents. Among the possible methods for accessing the mouse
      vasculature, tail vein injections are a routine but critical step for many
      experimental protocols. To perform successful tail vein injections, a high skill
      set and experience is required, leaving most scientists ill-suited to perform
      this task. This can lead to a high variability between injections, which can
      impact experimental results. To allow more scientists to perform tail vein
      injections and to decrease the variability between injections, a vascular access
      system (VAS) that semi-automatically inserts a needle into the tail vein of a
      mouse was developed. The VAS uses near infrared light, image processing
      techniques, computer controlled motors, and a pressure feedback system to insert
      the needle and to validate its proper placement within the vein. The VAS was
      tested by injecting a commonly used radiolabeled probe (FDG) into the tail veins
      of five mice. These mice were then imaged using micro-positron emission
      tomography to measure the percentage of the injected probe remaining in the tail.
      These studies showed that, on average, the VAS leaves 3.4% of the injected probe
      in the tail. With these preliminary results, the VAS system demonstrates the
      potential for improving the accuracy of tail vein injections in mice. 

PMID- 23877112
TI  - Functionalized single-walled carbon nanotube-based fuel cell benchmarked against
      US DOE 2017 technical targets.
AB  - Chemically modified single-walled carbon nanotubes (SWNTs) with varying degrees
      of functionalization were utilized for the fabrication of SWNT thin film catalyst
      support layers (CSLs) in polymer electrolyte membrane fuel cells (PEMFCs), which
      were suitable for benchmarking against the US DOE 2017 targets. Use of the
      optimum level of SWNT -COOH functionality allowed the construction of a prototype
      SWNT-based PEMFC with total Pt loading of 0.06 mg(Pt)/cm2--well below the value
      of 0.125 mg(Pt)/cm2 set as the US DOE 2017 technical target for total Pt group
      metals (PGM) loading. This prototype PEMFC also approaches the technical target
      for the total Pt content per kW of power (<0.125 g(PGM)/kW) at cell potential
      0.65 V: a value of 0.15 g(Pt)/kW was achieved at 80 degrees C/22 psig testing
      conditions, which was further reduced to 0.12 g(Pt)/kW at 35 psig back pressure.

PMID- 23877117
TI  - Metagenome-wide analysis of antibiotic resistance genes in a large cohort of
      human gut microbiota.
AB  - The human gut microbiota is a reservoir of antibiotic resistance genes, but
      little is known about their diversity and richness within the gut. Here we
      analyse the antibiotic resistance genes of gut microbiota from 162 individuals.
      We identify a total of 1,093 antibiotic resistance genes and find that Chinese
      individuals harbour the highest number and abundance of antibiotic resistance
      genes, followed by Danish and Spanish individuals. Single-nucleotide polymorphism
      based analysis indicates that antibiotic resistance genes from the two European
      populations are more closely related while the Chinese ones are clustered
      separately. We also confirm high abundance of tetracycline resistance genes with
      this large cohort study. Our study provides a broad view of antibiotic resistance
      genes in the human gut microbiota. 

PMID- 23877119
TI  - A new sensor for detection of CH3CN and ClCH2CN vapors based on vapoluminescent
      platinum(II) complex.
AB  - The planar platinum(II) complex [Pt(Me3SiC=CbpyC=CSiMe3)(C=CC6H4Et-4)2] (1) with
      5,5-bis(trimethylsilylethynyl)-2,2'-bipyridine was prepared and characterized.
      Solid-state 1 exhibits unusual, selective and reversible luminescence
      vapochromism to CH3CN and ClCH2CN vapors, which is useful for the detection of
      these hazardous vapors. A vapochromic cycle was monitored by dynamic variations
      in emission spectra and X-ray diffraction (XRD) patterns. Both X-ray
      crystallographic and density functional theory studies suggest that the
      vapochromic and vapoluminescent behavior of 1 are induced by the variation in the
      intermolecular Pt-Pt interactions.

PMID- 23877118
TI  - Neuronal surface and glutamic acid decarboxylase autoantibodies in
      Nonparaneoplastic stiff person syndrome.
AB  - IMPORTANCE: High titers of autoantibodies to glutamic acid decarboxylase (GAD)
      are well documented in association with stiff person syndrome (SPS). Glutamic
      acid decarboxylase is the rate-limiting enzyme in the synthesis of gamma
      aminobutyric acid (GABA), and impaired function of GABAergic neurons has been
      implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the
      causative agent or a disease marker. OBJECTIVE: To investigate the
      characteristics and potential pathogenicity of GAD autoantibodies in patients
      with SPS and related disorders. DESIGN: Retrospective cohort study and laboratory
      investigation. SETTING: Weatherall Institute of Molecular Medicine, University of
      Oxford. PARTICIPANTS: Twenty-five patients with SPS and related conditions
      identified from the Neuroimmunology Service. EXPOSURES: Neurological examination,
      serological characterization and experimental studies. MAIN OUTCOMES AND
      MEASURES: Characterization of serum GAD antibodies from patients with SPS and
      evidence for potential pathogenicity. RESULTS: We detected GAD autoantibodies at
      a very high titer (median, 7500 U/mL) in 19 patients (76%), including all 12
      patients with classic SPS. The GAD autoantibodies were high affinity (antibody
      dissociation constant, 0.06-0.78 nmol) and predominantly IgG1 subclass. The
      patients' autoantibodies co-localized with GAD on immunohistochemistry and in
      permeabilized cultured cerebellar GABAergic neurons, as expected, but they also
      bound to the cell surface of unpermeabilized GABAergic neurons. Adsorption of the
      highest titer (700 000 U/mL) serum with recombinant GAD indicated that these
      neuronal surface antibodies were not directed against GAD itself. Although
      intraperitoneal injection of IgG purified from the 2 available GAD autoantibody
      ositive purified IgG preparations did not produce clinical or pathological
      evidence of disease, SPS and control IgG were detected in specific regions of the
      mouse central nervous system, particularly around the lateral and fourth
      ventricles. CONCLUSIONS AND RELEVANCE: Autoantibodies to GAD are associated with
      antibodies that bind to the surface of GABAergic neurons and that could be
      pathogenic. Moreover, in mice, human IgG from the periphery gained access to
      relevant areas in the hippocampus and brainstem. Identification of the target of
      the non-GAD antibodies and peripheral and intrathecal transfer protocols,
      combined with adsorption studies, should be used to demonstrate the role of the
      non-GAD IgG in SPS.

PMID- 23877120
TI  - Darbepoetin inhibits proliferation of hepatic cancer cells in the presence of TGF
      beta.
AB  - Darbepoetin (DPO), an erythropoietin (EPO) derivative, was licensed in 2002 to
      treat patients with solid tumors suffering from chemotherapy-dependent anemia,
      although various tumors express EPO to improve vascularization, thus favoring
      tumor growth and spreading. Therefore, we wanted to investigate direct effects of
      DPO on the liver tumor cell lines HepG2, SkHep1, Huh-7, AKN1, HCC-T and HCC-M, as
      well as on primary human hepatocytes (hHeps). DPO (0-40 ng/ml) did not affect
      viability of hHeps, HepG2, SkHep1, AKN1, HCC-T and HCC-M cells, as determined by
      Resazurin conversion. However, Huh-7 cells' viability dose-dependently decreased
      from 5 ng/ml DPO on. Lack of LDH release into culture medium and negative DNA
      laddering excluded apoptosis or necrosis as the cause for the reduced Resazurin
      conversion. In Huh-7 cells, DPO increased the expression of p53. Interestingly,
      Huh-7 cells showed the highest basal TGF-beta1 expression as compared to the
      other cell lines. Upon inhibition of TGF-beta1 signaling, DPO no longer reduced
      viability in Huh-7 cells. On the contrary, co-incubation with TGF-beta1 made the
      other cell lines responsive to DPO. Summarizing our data, we show that DPO
      reduces the growth of Huh-7 cells by up-regulation of the tumor-suppressor gene
      p53. This mechanism seems to be dependent on a strong TGF-beta expression and
      corresponding signaling in these cells, as other cell lines became responsive to
      DPO with TGF-beta1 supplementation. The knowledge of this mechanism offers great
      perspectives for the understanding and treatment of solid liver tumors. 

PMID- 23877121
TI  - Suppression of erythropoietin induction by diethylstilbestrol in rats.
AB  - Diethylstilbestrol is an estrogenic endocrine disrupter that has diverse health
      effects in humans. Bisphenol A is another estrogen-like chemical with possible
      similar effects to diethylstilbestrol, which has been increasingly used for
      industry to lead to globally widespread human exposure to it. Hematopoiesis is
      another of their possible targets, since estrogen suppresses erythropoietin
      induction to induce anemia. The aim of this study was to clarify the effects of
      diethylstilbestrol and bisphenol A on erythropoietin induction in rats. We
      observed the effects of one-shot subcutaneous injection of diethylstilbestrol or
      bisphenol A on hypoxia-, bleeding-, and cobalt-stimulated erythropoietin
      induction within 24 h and the hematological outcomes after repeated subcutaneous
      injection of diethylstilbestrol three times a week for 1 month in rats.
      Diethylstilbestrol at 10-1,000 MUg/kg suppressed stimulus-elevated levels of
      plasma erythropoietin and its renal mRNA induction. In contrast, bisphenol A at
      1,000 MUg/kg did not suppress plasma erythropoietin elevated by any stimuli.
      Repeated injection of diethylstilbestrol at 1,000 MUg/kg to rats for 1 month
      induced an anemic trend due to decelerated erythropoiesis through the
      insufficient production of erythropoietin, mimicking the effects of estradiol. In
      conclusion, diethylstilbestrol has a suppressive effect on erythropoietin
      induction, leading to deceleration of erythropoiesis and the development of
      anemia. 

PMID- 23877122
TI  - Effects of N-acetyl-L-cysteine on target sites of hydroxylated fullerene-induced
      cytotoxicity in isolated rat hepatocytes.
AB  - The effects of N-acetyl-L-cysteine (NAC) on cytotoxicity caused by a hydroxylated
      fullerene [C60(OH)24], which is known a nanomaterial and/or a water-soluble
      fullerene derivative, were studied in freshly isolated rat hepatocytes. The
      exposure of hepatocytes to C60(OH)24 at a concentration of 0.1 mM caused time (0
      3 h)-dependent cell death accompanied by the formation of cell blebs, loss of
      cellular ATP, and reduced glutathione (GSH) and protein thiol levels, as well as
      the accumulation of glutathione disulfide and malondialdehyde (MDA), indicating
      lipid peroxidation. Despite this, C60(OH)24-induced cytotoxicity was effectively
      prevented by NAC pretreatment ranging in concentrations from 1 to 5 mM. Further,
      the loss of mitochondrial membrane potential (MMP) and generation of oxygen
      radical species in hepatocytes incubated with C60(OH)24 were inhibited by
      pretreatment with NAC, which caused increases in cellular and/or mitochondrial
      levels of GSH, accompanied by increased levels of cysteine via enzymatic
      deacetylation of NAC. On the other hand, severe depletion of cellular GSH levels
      caused by diethyl maleate at a concentration of 1.25 mM led to the enhancement of
      C60(OH)24-induced cell death accompanied by a rapid loss of ATP. Taken
      collectively, these results indicate that pretreatment with NAC ameliorates (a)
      mitochondrial dysfunction linked to the depletion of ATP, MMP, and mitochondrial
      GSH level and (b) induction of oxidative stress assessed by reactive oxygen
      species generation, losses of intracellular GSH and protein thiol levels, and MDA
      formation caused by C60(OH)24, suggesting that the onset of toxic effects is at
      least partially attributable to a thiol redox-state imbalance as well as
      mitochondrial dysfunction related to oxidative phosphorylation. 

PMID- 23877124
TI  - The impact of pharyngeal fat tissue on the pathogenesis of obstructive sleep
      apnea.
AB  - PURPOSE: Obesity is the most important risk factor for obstructive sleep apnea
      (OSA); however, the exact underlying mechanisms are still not fully understood.
      The aim of this study was to examine the morphology of upper airways in
      overweight habitual snorers and in mild OSA patients. Furthermore, the
      associations between weight loss, parapharyngeal fat pad area and OSA were
      assessed in a 1-year randomised, controlled follow-up study originally conducted
      to determine the effects of lifestyle changes with weight reduction as a
      treatment of OSA. METHODS: Thirty-six overweight adult patients with mild OSA
      [apnea-hypopnea index (AHI) 5-15 events/h] and 24 weight-matched habitual snorers
      (AHI < 5 events/h) were included in the study. All patients underwent nocturnal
      cardiorespiratory recordings and multislice computed tomography (CT) of
      parapharyngeal fat pad area, the smallest diameter and area in naso-, oro- and
      hypopharynx, the smallest diameter and area of the whole pharyngeal airway, the
      distance from the hyoid bone to the mandibular plane and to cervical tangent as
      well as the distance between mandibular symphysis and cervical spine. In
      addition, OSA patients were further randomised to receive either an active 1-year
      lifestyle intervention with an early weight loss programme or routine lifestyle
      counselling. After 1 year, the cardiorespiratory recordings and CT scans were
      repeated. RESULTS: The pharyngeal fat pad area was significantly larger, and the
      distance from the hyoid bone to cervical spine was longer in patients with OSA
      than in habitual snorers (p = 0.002 and p = 0.018, respectively). The multiple
      regression analysis showed that besides a large pharyngeal fat pad area and a
      long distance from the cervical spine to hyoid bone, also a short distance from
      the mandibular symphysis to cervical tangent increased a risk to OSA. During the
      1-year follow-up in OSA patients, the pharyngeal fat pad area and AHI decreased
      significantly in the intervention group (p = 0.003 and p < 0.001, respectively).
      CONCLUSIONS: In the early stages of OSA, the pharyngeal fat pad seems to play an
      important role in the development of disease in overweight patients. Furthermore,
      weight reduction by lifestyle intervention-based programme reduces both central
      obesity and pharyngeal fat pads, resulting in an improvement of OSA.

PMID- 23877125
TI  - An approach for characterizing and comparing hyperspectral microscopy systems.
AB  - Hyperspectral imaging and analysis approaches offer accurate detection and
      quantification of fluorescently-labeled proteins and cells in highly
      autofluorescent tissues. However, selecting optimum acquisition settings for
      hyperspectral imaging is often a daunting task. In this study, we compared two
      hyperspectral systems-a widefield system with acoustic optical tunable filter
      (AOTF) and charge coupled device (CCD) camera, and a confocal system with
      diffraction gratings and photomultiplier tube (PMT) array. We measured the
      effects of system parameters on hyperspectral image quality and linear unmixing
      results. Parameters that were assessed for the confocal system included pinhole
      diameter, laser power, PMT gain and for the widefield system included arc lamp
      intensity, and camera gain. The signal-to-noise ratio (SNR) and the root-mean
      square error (RMS error) were measured to assess system performance.
      Photobleaching dynamics were studied. Finally, theoretical sensitivity studies
      were performed to estimate the incremental response (sensitivity) and false
      positive detection rates (specificity). Results indicate that hyperspectral
      imaging assays are highly dependent on system parameters and experimental
      conditions. For detection of green fluorescent protein (GFP)-expressing cells in
      fixed lung tissues, a confocal pinhole of five airy disk units, high excitation
      intensity and low detector gain were optimal. The theoretical sensitivity studies
      revealed that widefield hyperspectral microscopy was able to detect GFP with
      fewer false positive occurrences than confocal microscopy, even though confocal
      microscopy offered improved signal and noise characteristics. These studies
      provide a framework for optimization that can be applied to a variety of
      hyperspectral imaging systems. 

PMID- 23877127
TI  - Investigation of tree spectral reflectance characteristics using a mobile
      terrestrial line spectrometer and laser scanner.
AB  - In mobile terrestrial hyperspectral imaging, individual trees often present large
      variations in spectral reflectance that may impact the relevant applications, but
      the related studies have been seldom reported. To fill this gap, this study was
      dedicated to investigating the spectral reflectance characteristics of individual
      trees with a Sensei mobile mapping system, which comprises a Specim line
      spectrometer and an Ibeo Lux laser scanner. The addition of the latter unit
      facilitates recording the structural characteristics of the target trees
      synchronously, and this is beneficial for revealing the characteristics of the
      spatial distributions of tree spectral reflectance with variations at different
      levels. Then, the parts of trees with relatively low-level variations can be
      extracted. At the same time, since it is difficult to manipulate the whole
      spectrum, the traditional concept of vegetation indices (VI) based on some
      particular spectral bands was taken into account here. Whether the assumed VIs
      capable of behaving consistently for the whole crown of each tree was also
      checked. The specific analyses were deployed based on four deciduous tree species
      and six kinds of VIs. The test showed that with the help of the laser scanner
      data, the parts of individual trees with relatively low-level variations can be
      located. Based on these parts, the relatively stable spectral reflectance
      characteristics for different tree species can be learnt. 

PMID- 23877126
TI  - Fabrication of an SPR sensor surface with antifouling properties for highly
      sensitive detection of 2,4,6-trinitrotoluene using surface-initiated atom
      transfer polymerization.
AB  - In this study, we modified a surface plasmon resonance immunosensor chip with a
      polymer using surface-initiated atom transfer polymerization (SI-ATRP) for the
      highly sensitive detection of 2,4,6-trinitrotoluene (TNT). To immobilize a TNT
      analogue on the polymer, mono-2-(methacryloyloxy)ethylsuccinate (MES), which has
      a carboxyl group, was used in this study. However, the anti-TNT antibody may
      adsorb non-specifically on the polymer surface by an electrostatic interaction
      because MES is negatively charged. Therefore, a mixed monomer with MES and
      diethylaminoethylmethacrylate (DEAEM), which has a tertiary amino group and is
      positively charged, was prepared to obtain electroneutrality for suppressing the
      nonspecific adsorption. The detection of TNT was performed by inhibition assay
      using the polymer surface. To ensure high sensitivity to TNT, the affinity
      between the surface and the antibody was optimized by controlling the density of
      the initiator for ATRP by mixing two types of self-assembled monolayer reagents.
      As a result, a limit of detection of 5.7 pg/mL (ppt) for TNT was achieved using
      the optimized surface. 

PMID- 23877128
TI  - Three dimensional gait analysis using wearable acceleration and gyro sensors
      based on quaternion calculations.
AB  - This paper proposes a method for three dimensional gait analysis using wearable
      sensors and quaternion calculations. Seven sensor units consisting of a tri-axial
      acceleration and gyro sensors, were fixed to the lower limbs. The acceleration
      and angular velocity data of each sensor unit were measured during level walking.
      The initial orientations of the sensor units were estimated using acceleration
      data during upright standing position and the angular displacements were
      estimated afterwards using angular velocity data during gait. Here, an algorithm
      based on quaternion calculation was implemented for orientation estimation of the
      sensor units. The orientations of the sensor units were converted to the
      orientations of the body segments by a rotation matrix obtained from a
      calibration trial. Body segment orientations were then used for constructing a
      three dimensional wire frame animation of the volunteers during the gait. Gait
      analysis was conducted on five volunteers, and results were compared with those
      from a camera-based motion analysis system. Comparisons were made for the joint
      trajectory in the horizontal and sagittal plane. The average RMSE and correlation
      coefficient (CC) were 10.14 deg and 0.98, 7.88 deg and 0.97, 9.75 deg and 0.78
      for the hip, knee and ankle flexion angles, respectively. 

PMID- 23877129
TI  - Sensors and sensory processing for airborne vibrations in silk moths and
      honeybees.
AB  - Insects use airborne vibrations caused by their own movements to control their
      behaviors and produce airborne vibrations to communicate with conspecific mates.
      In this review, I use two examples to introduce how insects use airborne
      vibrations to accurately control behavior or for communication. The first example
      is vibration-sensitive sensilla along the wing margin that stabilize wingbeat
      frequency. There are two specialized sensors along the wing margin for detecting
      the airborne vibration caused by wingbeats. The response properties of these
      sensors suggest that each sensor plays a different role in the control of
      wingbeats. The second example is Johnston's organ that contributes to regulating
      flying speed and perceiving vector information about food sources to hive-mates.
      There are parallel vibration processing pathways in the central nervous system
      related with these behaviors, flight and communication. Both examples indicate
      that the frequency of airborne vibration are filtered on the sensory level and
      that on the central nervous system level, the extracted vibration signals are
      integrated with other sensory signals for executing quick adaptive motor
      response. 

PMID- 23877130
TI  - ARC is highly expressed in nasopharyngeal carcinoma and confers X-radiation and
      cisplatin resistance.
AB  - Apoptosis repressor with caspase recruitment domain (ARC), an inhibitor of
      apoptosis, is primarily expressed in terminally differentiated tissues. Recent
      studies have revealed that ARC is highly expressed in a variety of human cancer
      cell lines and epithelial-derived cancers, which suggests that ARC plays an
      important role in the process of carcinogenesis. However, whether ARC is involved
      in the development of nasopharyngeal carcinoma (NPC) and the various roles it
      plays in NPC remain unclear. In the present study, we examined the expression of
      ARC in NPC cell lines and NPC tissues and the relationship between its
      subcellular expression and clinicopathological grade; moreover, we explored the
      effect of this protein on radiation resistance and chemoresistance in NPC cells.
      We found that cytoplasmic ARC was expressed at high levels in NPC tissues, at
      moderate levels in severe atypical hyperplasia and at low levels in benign
      nasopharyngeal tissues. High expression of cytoplasmic and nuclear ARC was
      correlated with advanced local invasion. However, only a small amount of nuclear
      ARC was expressed in NPC in contrast to cytoplasmic ARC. We also found that
      attenuation of ARC expression by miRNA resulted in decreased X-radiation and
      cisplatin resistance in NPC CNE-2 cells. In contrast, overexpression of ARC
      resulted in increased X-radiation and cisplatin resistance in NPC 6-10B cells.
      Furthermore, we demonstrated that ARC appears to be critical for blocking the
      activation of casapse-8 and casapse-2 in NPC cells subjected to X-radiation or
      cisplatin. These results suggest that high expression of ARC plays an important
      role in the pathogenesis of NPC and leads to X-radiation and cisplatin resistance
      in NPC. 

PMID- 23877131
TI  - Sintering-resistant Ni-based reforming catalysts obtained via the nanoconfinement
      effect.
AB  - This communication describes the design and synthesis of anti-sintering and -coke
      nickel phyllosilicate (PS) nanotubes (Ni/PSn) for hydrogen production via
      reforming reactions. The introduction of nickel particles in PS nanotubes could
      effectively maintain the Ni size and increase the resistance of metal particles
      for carbon deposition. 

PMID- 23877132
TI  - Gene patents: a broken incentives system.
AB  - The proliferation of patents on human genes has raised important ethical
      questions centered on the conflict of patient rights and intellectual property
      rights. With the Supreme Court's June 2013 decision that altered the patent
      eligibility of genetic material, it is important to reexamine the ethical
      implications of gene patents as a concept. Such patents suggest an ownership of
      genetic material that may hinder access to healthcare and inhibit medical
      progress. The application of the current patent system to genetic material thus
      violates patients' rights without fulfilling the system's goal of promoting
      innovation, suggesting a need for a revised incentives infrastructure. 

PMID- 23877133
TI  - GSTM1 and GSTT1 null polymorphisms and male infertility risk: an updated meta
      analysis encompassing 6934 subjects.
AB  - Published data on the association between the GST genes polymorphisms and male
      infertility risk are inconclusive. We investigated GST genes polymorphisms in a
      large sample size case-control study, and conducted a literature-based meta
      analysis of 6934 individuals. Our case-control study showed the GSTM1 null
      genotype was significantly associated with idiopathic oligozoospermia, while the
      null genotype of GSTT1 was significantly associated with normozoospermia and
      azoospermia. Additionally, significantly elevated GSTT1 expression levels were
      observed in present genotype compared with null genotype. In the meta-analysis,
      the null genotype of GSTM1 was associated with a significantly increased risk of
      male infertility. Furthermore, a stratification analysis showed that the risk of
      GSTM1 polymorphism was associated with male infertility in both Asian and
      Caucasian groups. Further studies of GSTM1 and GSTT1 with their biological
      functions are needed to understand the role of these genes in the development of
      male infertility. 

PMID- 23877134
TI  - What do we know about one-to-one peer support for adults with a burn injury? A
      scoping review.
AB  - The purpose of this study was to conduct a broad examination of the central
      themes and concepts associated with one-to-one peer support for adult patients
      with a burn injury. The aim of the synthesis was to examine 1) what is reported
      in the literature regarding the impact of peer support for patients or peers and
      2) what methods or elements were considered important with regard to the program
      design and structure. The synthesis undertaken for this study followed scoping
      review methodology. A systematic search of the literature was undertaken to
      identify articles of relevance. Four databases were searched: MEDLINE (medicine),
      Embase (medicine), PsychINFO (psychology), and SWAbstracts (social work).
      Information pertaining to program design and structure, recruitment and screening
      requirements, and perceived benefits and risks associated with peer support were
      extracted from the included articles. Nine key themes pertaining to program
      design and structure, and 10 key themes relating to the impact of peer support
      for patients or peers were identified and discussed. One-to-one peer support for
      adults with burns trauma has the potential to be a unique support option with
      earnest attributes. The preliminary data representing the effects of peer support
      for adults with a burn injury as presented in this literature review shows an
      emerging pattern of benefit for givers and receivers of peer support. Further
      work is needed in this field and recommendations are made for future studies. 

PMID- 23877135
TI  - Disaster planning: the basics of creating a burn mass casualty disaster plan for
      a burn center.
AB  - In 2005, the American Burn Association published burn disaster guidelines. This
      work recognized that local and state assets are the most important resources in
      the initial 24- to 48-hour management of a burn disaster. Historical experiences
      suggest there is ample opportunity to improve local and state preparedness for a
      major burn disaster. This review will focus on the basics of developing a burn
      surge disaster plan for a mass casualty event. In the event of a disaster, burn
      centers must recognize their place in the context of local and state disaster
      plan activation. Planning for a burn center takes on three forms;
      institutional/intrafacility, interfacility/intrastate, and interstate/regional.
      Priorities for a burn disaster plan include: coordination, communication, triage,
      plan activation (trigger point), surge, and regional capacity. Capacity and
      capability of the plan should be modeled and exercised to determine limitations
      and identify breaking points. When there is more than one burn center in a given
      state or jurisdiction, close coordination and communication between the burn
      centers are essential for a successful response. Burn surge mass casualty
      planning at the facility and specialty planning levels, including a state burn
      surge disaster plan, must have interface points with governmental plans. Local,
      state, and federal governmental agencies have key roles and responsibilities in a
      burn mass casualty disaster. This work will include a framework and critical
      concepts any burn disaster planning effort should consider when developing future
      plans. 

PMID- 23877136
TI  - PNU-282987 improves the hemodynamic parameters by alleviating vasopermeability
      and tissue edema in dogs subjected to a lethal burns shock.
AB  - Excessive inflammation and high vasopermeability can lead to blood volume loss
      and tissue edema, which can affect the resuscitation and prognosis for serious
      burn patients. In this experiment, we investigated the effect of PNU-282987, an
      alpha7 nicotine cholinergic receptor agonist on the hemodynamic parameters and
      survival rate by inhibiting vasopermeability and tissue edema during the fluid
      resuscitation for lethal burn shock. Forty Beagle dogs with intubation of the
      carotid artery and jugular vein 24 hours before the injury were subjected to 50%
      TBSA full-thickness burns, and were randomly divided into following four groups:
      no resuscitation group (group NR), venous fluid resuscitation group (group R),
      PNU-282987 treatment group (group P), and fluid resuscitation group plus PNU
      282987 group (group RP), with 10 dogs in each group. Hemodynamic variables and
      biochemical parameters were determined with animals in a conscious and
      cooperative state. The plasma volume and the vasopermeability were determined by
      indocyanine green and fluorescein isothiocyanate-dextran, respectively. The level
      of tumor necrosis factor-alpha and interleukin-1beta in plasma, and the water
      content of different organs were also determined. The mean arterial pressure,
      cardiac output, and plasma volume of all dogs decreased significantly, and the
      lung extravascular water index and pulmonary vascular permeability index
      increased remarkably after burn. The hemodynamic parameters deteriorated
      continually in group N dogs, and then anuria, hyperlactacidemia, and multiple
      organ dysfunctions developed. The mean arterial pressure and cardiac output of
      dogs in group R and group RP returned to preinjury levels at 48 hours postburn.
      The lung extravascular water index and pulmonary vascular permeability in group R
      were higher than those before preinjury. The dogs in group RP were found to have
      a significant increase in plasma volume and urine output, and a remarkable
      decrease in the levels of tumor necrosis factor-alpha, interleukin-1alpha, lactic
      acid, and organ functions compared with those of group R (P <.05). The survival
      rate of RP group (100%; 10/10) was significantly higher than that of group N (0;
      0/10), group P (20%; 2/10), and group R (60%; 6/10). PNU-282987 combined with
      intravenous fluid resuscitation significantly improved hemodynamics and the
      survival rate in the early period after this lethal burn shock. The mechanism may
      be attributable to the lowering of the level of proinflammatory mediators,
      amelioration of vasopermeability-induced visceral edema, less of blood volume
      loss, and protection of vital organs through activation of cholinergic anti
      inflammatory pathway. 

PMID- 23877137
TI  - Young children's perceptions of fire-safety messages: do framing and parental
      mediation matter?
AB  - Media can deliver health and safety messages promoting child health and injury
      prevention. This study examined the effects of message framing and parental
      mediation on children's perceptions of fire-safety messages. Using a 2 * 3
      randomized experimental design, this study considered both message framing (gain
      or loss) and parental mediation (no mediation/control, unscripted, or scripted)
      with 320 children who were 4 and 5 years of age. Children saw two messages (burn
      and smoke inhalation) embedded in a cartoon. Afterward, researchers assessed
      children's recall, understanding, and perceptions of self-efficacy and social
      norms. Children were more likely to recall the safety messages if they were older
      (burn: adjusted odds ration [AOR] = 2.74 and smoke: AOR = 2.58), and could recall
      the smoke inhalation message if they had unscripted mediation (AOR = 3.16).
      Message understanding was poor, with only about 50% of children choosing a
      correct behavior in a similar scenario. For the burn message, correct
      understanding was associated with gain-framing and scripted mediation (AOR = 3.22
      and 5.77, respectively). Only the scripted mediation group was significantly
      associated with an increase in perceived social norms (burn: coefficient =.37 and
      smoke: coefficient =.55; P <.001. Gain-framing was associated with increased odds
      of self-efficacy for both behaviors (burn: AOR = 1.77 and smoke: AOR = 1.77).
      Messages that show positive outcomes combined with scripted parental mediation
      appear most effective in communicating safety behaviors, but the overall
      effectiveness of video-based messages to teach children safety behaviors needs to
      be enhanced. 

PMID- 23877138
TI  - Alkali-related ocular burns: a case series and review.
AB  - Alkali burns are known to possess high pathological potential because of their
      inherent ability to lyse cell membranes and penetrate intraocular structures with
      devastating results. The authors aimed to evaluate the most common cause of this
      presentation, the current treatment approaches to injury, and eventual outcome as
      related to severity. The authors performed a retrospective review of all patients
      who sustained chemical-related ocular injuries seen at the Concord Hospital Burns
      Unit, Australia between January 2005 and March 2012. Management was based on
      cooperation between ophthalmic staff and the burns unit, with emphasis on early
      aggressive intervention and rigorous follow-up. The records of 39 patients who
      presented with chemical-related injury were assessed, 12 of whom had confirmed
      alkali burns involving the cornea. The most commonly implicated agent was sodium
      hydroxide, usually in the context of otherwise trivial domestic accidents. Acute
      medical management included copious irrigation and the use of analgesics,
      cycloplegics, and topical antibiotics. In half the cases, steroid drops and oral
      vitamin C were also used. Ten of the 12 patients (83%) had return to premorbid
      visual acuity. Complications included cicatrical ectropion (n = 1),
      pseudoexfoliative syndrome (n = 1), and symblepharon (n = 1). Surgical correction
      was needed in the one patient with cicatrical ectropion. This case series shows
      that appropriate acute management minimizes the potentially devastating sequelae
      of ocular alkali burns. Emphasis should be placed on prevention of domestic and
      workplace injuries when using alkaline products. 

PMID- 23877139
TI  - Prevalence and impact of late defecation in the critically ill, thermally injured
      adult patient.
AB  - The aim of this study was to determine the prevalence of late defecation (absence
      of laxation for more than 6 days after admission) as an indicator of lower
      gastrointestinal (GI) tract dysfunction in burn patients. In addition, the
      authors wanted to determine whether the addition of polyethylene glycol 3350 to
      the standard bowel regimen led to improvement in markers of lower-GI function and
      outcomes. The authors conducted a retrospective chart review of patients admitted
      to the burn intensive care unit during a 26-month period. Inclusion criteria were
      20% or more TBSA burn, requirement for mechanical ventilation, and age over 18
      years. Of 83 patients included, the prevalence of late defecation was 36.1% (n =
      30). There was no association between late defecation and mortality. Patients
      with late defecation had more frequent episodes of constipation after first
      defecation (P =.03), of feeding intolerance (P =.007), and received total
      parenteral nutrition more frequently (P =.005). The addition of polyethylene
      glycol to the standard bowel regimen did not affect markers of lower-GI function.
      Late defecation occurs in more than one third of critically ill burn patients.
      Late defecation was associated with ongoing lower-GI dysfunction, feeding
      intolerance, and the use of total parenteral nutrition. The causal relationship
      between these problems has not been determined. A prospective study at the
      authors' institution is currently planned to attempt to validate late defecation
      as a marker of lower-GI tract dysfunction, determine its relationship to various
      outcomes, and determine risk factors for its development. 

PMID- 23877141
TI  - Challenging the dogma: relationship between time to healing and formation of
      hypertrophic scars after burn injuries.
AB  - Hypertrophic scarring (HTS) is defined as a scar, which is raised above the skin
      level and remains within the confines of the original lesion. The authors
      hypothesize that small surface area burns can be left to heal beyond 21 days
      without an increase in the incidence of HTS formation, within the confines of a
      carefully selected patient population. The authors have documented the number of
      days to healing in all patients conservatively managed in their outpatient burns
      clinic. All patients who took longer than 21 days to heal receive a follow-up
      telephone call. A multivariate regression analysis is used to confirm significant
      factors that impede healing time. This study included 181 conservatively managed
      burns with a male:female ratio of 1.63:1 and average age of 24.7 +/- 21.69 years
      (range, 1 month to 85 years). In total, 32 patients (18%) took more than 21 days
      to heal (range, 22-88 days), of which five patients presented with HTS (days to
      healing range, 23-47; one mixed depth and four deep dermal). One patient did not
      attend for follow-up, two patients settled with silicone gel alone whereas one
      settled with pressure garments. One patient is still being seen. The only
      significant factor in predicting time to healing in the ANOVA model in this study
      was depth of burn (P = .01; confidence interval, 1.18-6.07). Advances in wound
      care and better understanding of the physiological processes involved in healing
      may now enable the management of smaller burns with dressings, delaying the need
      for early surgical debridement and skin grafting in certain individuals.

PMID- 23877140
TI  - Wound coverage technologies in burn care: novel techniques.
AB  - Improvements in burn wound care have vastly decreased morbidity and mortality in
      severely burned patients. Development of new therapeutic approaches to increase
      wound repair has the potential to reduce infection, graft rejection, and
      hypertrophic scarring. The incorporation of tissue-engineering techniques, along
      with the use of exogenous proteins, genes, or stem cells to enhance wound
      healing, heralds new treatment regimens based on the modification of already
      existing biological activity. Refinements to surgical techniques have enabled the
      creation of protocols for full facial transplantation. With new technologies and
      advances such as these, care of the severely burned will undergo massive changes
      over the next decade. This review centers on new developments that have recently
      shown great promise in the investigational arena. 

PMID- 23877142
TI  - Evaluation of an oxygen-diffusion dressing for accelerated healing of donor-site
      wounds.
AB  - Accelerating the healing process and reducing pain during healing are beneficial
      for the following reasons: faster return to work, lower risk of wound infection,
      improved quality of life, and possibly reduced need for analgesia. This clinical
      study assessed the effectiveness of a new oxygen-diffusion dressing (OxyBand;
      Oxyband Technologies, St. Louis, MO) compared with standard Xeroform gauze
      dressings (Convidien, Mansfield, MA), in the care of skin-graft donor sites in
      burn patients. Time to healing was the primary endpoint, and pain scores and
      cosmetic outcome were also assessed. This was a prospective, randomized,
      controlled study of burn patients undergoing harvesting of two donor sites.
      Patients were followed at predetermined time points for 30 to 45 days to
      determine the time to reepithelialization, cosmetic appearance, and pain.
      Subjects were adult burn patients with less than 30% TBSA burns admitted to the
      burn center, who required excision and grafting. Twenty patients were enrolled,
      of whom 17 completed the study. Average age was 35 years. Average burn size was
      9.2% TBSA. Patients underwent harvesting of split-thickness skin grafts with one
      donor wound dressed with OxyBand and the other dressed in Xeroform gauze. Wounds
      were inspected and photographed on postoperative days 4 and 8, and then every 2
      days until the donor wounds were healed. Pain scores at each site were also
      collected at these visits (rated by patients on a scale from 0 to 10). Mean time
      to wound healing for OxyBand was 9.3 +/- 1.7 days; for Xeroform, 12.4 +/- 2.7
      days (P < .001). Pain scores were lower (P < .01) at the OxyBand site compared
      with the Xeroform site at all time points during postoperative days 4 to 12.
      There was no difference in the cosmetic outcome of the wounds at 30 to 45 days
      postoperatively. This study revealed a decrease in the time to healing and in
      pain at donor sites dressed with an oxygen-diffusion dressing. 

PMID- 23877143
TI  - Characterizing demographics, injury severity, and intubation status for patients
      transported by air or ground ambulance to a rural burn center.
AB  - Our study was designed to characterize intubation status among patients
      transported by air or ground ambulance to a rural burn center. A retrospective
      chart review of patients arriving at our burn center from January 1, 2005 to
      December 31, 2009 was completed. Descriptive and multivariate analyses were
      performed. During the study period, 259 air and 590 ground ambulance patients met
      inclusion criteria. Air ambulance patients were older and had higher total body
      surface area burned, lower Glasgow Coma scores, longer lengths of stay, and more
      frequent inhalation injuries. Approximately 10% of patients arriving by air were
      intubated after burn center admission, and 49% of intubated patients were
      extubated within 24 hours of admission. These values were 2% and 40%,
      respectively, for patients transported by ground. Increasing age and air
      ambulance transport increased the overall likelihood of change in intubation
      status. The likelihood of intubation by burn center providers increased with age,
      with suspicion of inhalation injury, and for patients transported by air. The
      likelihood of extubation within 24 hours of burn center admission increased with
      age, decreased with suspected inhalation injury, and was independent of transport
      mode. Among our patient population, more severely injured patients were being
      transported by air ambulance. However, age, suspicion of inhalation injury, and
      mode of transport showed a complex pattern of associations with changes in
      intubation status, and illustrate the need to develop better prehospital
      guidelines for intubation in burn patients. 

PMID- 23877145
TI  - Proposing "the burns suite" as a novel simulation tool for advancing the delivery
      of burns education.
AB  - Educational theory highlights the importance of contextualized simulation for
      effective learning. We explored this concept in a burns scenario in a novel, low
      cost, high-fidelity, portable, immersive simulation environment (referred to as
      distributed simulation). This contextualized simulation/distributed simulation
      combination was named "The Burns Suite" (TBS). A pediatric burn resuscitation
      scenario was selected after high trainee demand. It was designed on Advanced
      Trauma and Life Support and Emergency Management of Severe Burns principles and
      refined using expert opinion through cognitive task analysis. TBS contained
      "realism" props, briefed nurses, and a simulated patient. Novices and experts
      were recruited. Five-point Likert-type questionnaires were developed for face and
      content validity. Cronbach's alpha was calculated for scale reliability.
      Semistructured interviews captured responses for qualitative thematic analysis
      allowing for data triangulation. Twelve participants completed TBS scenario. Mean
      face and content validity ratings were high (4.6 and 4.5, respectively; range, 4
      5). The internal consistency of questions was high. Qualitative data analysis
      revealed that participants felt 1) the experience was "real" and they were "able
      to behave as if in a real resuscitation environment," and 2) TBS "addressed what
      Advanced Trauma and Life Support and Emergency Management of Severe Burns didn't"
      (including the efficacy of incorporating nontechnical skills). TBS provides a
      novel, effective simulation tool to significantly advance the delivery of burns
      education. Recreating clinical challenge is crucial to optimize simulation
      training. This low-cost approach also has major implications for surgical
      education, particularly during increasing financial austerity. Alternative
      scenarios and/or procedures can be recreated within TBS, providing a diverse
      educational immersive simulation experience. 

PMID- 23877144
TI  - Adenosine triphosphate hydrolysis reduces neutrophil infiltration and necrosis in
      partial-thickness scald burns in mice.
AB  - Extracellular adenosine triphosphate (ATP), present in thermally injured tissue,
      modulates the inflammatory response and causes significant tissue damage. The
      authors hypothesize that neutrophil infiltration and ensuing tissue necrosis
      would be mitigated by removing ATP-dependent signaling at the burn site. Mice
      were subjected to 30% TBSA partial-thickness scald burn by dorsal skin immersion
      in a water bath at 60 or 20 degrees C (nonburn controls). In the treatment arm,
      an ATP hydrolyzing enzyme, apyrase, was applied directly to the site immediately
      after injury. Skin was harvested after 24 hours and 5 days for hematoxylin and
      eosin stain, elastase, and Ki-67 staining. Tumor necrosis factor (TNF)-alpha and
      interferon (IFN)-beta expression were measured through quantitative real-time
      polymerase chain reaction. At 24 hours, the amount of neutrophil infiltration was
      different between the burn and burn + apyrase groups (P < .001). Necrosis was
      less extensive in the apyrase group when compared with the burn group at 24 hours
      and 5 days. TNF-alpha and IFN-beta expression at 24 hours in the apyrase group
      was lower than in the burn group (P < .05). However, Ki-67 signaling was not
      significantly different among the groups. The results of this study support the
      role of extracellular ATP in neutrophil activity. The authors demonstrate that
      ATP hydrolysis at the burn site allays the neutrophil response to thermal injury
      and reduces tissue necrosis. This decrease in inflammation and tissue necrosis is
      at least partially because of TNF-alpha and IFN-beta signaling. Apyrase could be
      used as topical inflammatory regulators to quell the injury caused by
      inflammation. 

PMID- 23877146
TI  - Use of cyanide antidotes in burn patients with suspected inhalation injuries in
      North America: a cross-sectional survey.
AB  - This study aimed to assess the use of cyanide antidotes and the determine the
      opinion on empiric administration of hydroxocobalamin in North American burn
      patients with suspected smoke inhalation injuries. An online cross-sectional
      survey was sent to directors of 90 major burn centers in North America, which
      were listed on the American Burn Association Web site. A multiple-choice format
      was used to determine the percentage of patients tested for cyanide poisoning on
      admission, the current administration of a cyanide antidote based solely on
      clinical suspicion of poisoning, and the antidote used. To ascertain views on
      immediate administration of hydroxocobalamin before confirmation of cyanide
      poisoning an option was included to expand the response in written format. Twenty
      nine of 90 burn directors (32%) completed the survey. For the population of
      interest, the majority of burn centers (59%) do not test for cyanide poisoning on
      admission and do not administer an antidote based solely on clinical suspicion of
      cyanide poisoning (58%). The most commonly available antidote is hydroxocobalamin
      (50%), followed by the cyanide antidote kit (29%). The opinion regarding instant
      administration of hydroxocobalamin when inhalation injury is suspected is mixed:
      31% support its empiric use, 17% do not, and the remaining 52% have varying
      degrees of confidence in its utility. In North America, most patients burnt in
      closed-space fires with inhalation injuries are neither tested for cyanide
      poisoning in a timely manner nor empirically treated with a cyanide antidote.
      Although studies have shown the safety and efficacy of empiric and immediate
      administration of hydroxocobalamin, most centers are not willing to do so.

PMID- 23877147
TI  - Use of methylnaltrexone to induce laxation in acutely injured patients with burns
      and necrotizing soft-tissue infections.
AB  - The routine use of high-dose opioids for analgesia in patients with acute burns
      and soft-tissue injuries often leads to the development of opioid-induced
      constipation. The opioid antagonist methylnaltrexone (MLTX) reverses narcotic
      related ileus without affecting systemic pain treatment. The authors' burn center
      developed a bowel protocol that included administration of MLTX for relief of
      opioid-induced constipation after other methods failed. The authors performed a
      retrospective review of patients with acute burns or necrotizing soft-tissue
      infections, who had been given subcutaneous MLTX to induce laxation. All patients
      who received MLTX were included and all administrations of the drug were included
      in the analysis. The primary outcome examined was time to laxation from drug
      administration. Forty-eight patients received MLTX a total of 112 times. Six
      patients were admitted with soft-tissue injuries and the rest suffered burns with
      an average TBSA of 17%. The median patient age was 41 years and the majority
      (75%) were men. Administration of a single dose of MLTX resulted in laxation
      within 4 hours in 38% of cases, and within 24 hours in 68%. Patients given MLTX
      received an average of 174 mg morphine equivalents daily for pain control. MLTX
      was given after an average of 52 hours since the last bowel movement. As this
      experience has evolved, it has been incorporated into an organized bowel
      protocol, which includes MLTX administration after other laxatives have failed.
      MLTX is an effective laxation agent in patients with burn and soft-tissue
      injuries, who have failed conventional agents.

PMID- 23877148
TI  - Electrodiagnostic study of peripheral nerves in high-voltage electrical injury.
AB  - It is well known that peripheral nerves are very vulnerable to electricity.
      However, only a small portion of individuals who have had high-voltage electrical
      injury exhibit peripheral nerve damage. The aim of this study was to investigate
      peripheral nerve damage in high-voltage electrical injury, which often occurs in
      the industrial field. The authors reviewed the medical records of patients who
      were admitted to their hospital from January 2009 to December 2011, because of
      electrical injuries. The results of nerve conduction studies (NCSs) were reviewed
      retrospectively. NCS data of the injured site were compared with those of the
      opposite noninjured site and follow-up data. Thirty-seven extremities were
      reviewed. The authors found that 18 of 33 median nerves (48.6%) showed
      abnormalities in at least one parameter and 15 of 36 ulnar nerves (41.7%)
      exhibited abnormalities. There was no evidence of demyelination. Eight patients
      had undergone NCS on the opposite normal extremities. The compound muscle action
      potential and nerve conduction velocity were higher at the normal site. Follow-up
      NCS were performed in 14 patients: the compound muscle action potential and nerve
      conduction velocity values of all patients were improved. High-voltage
      electricity damaged peripheral nerves by causing axonal injury rather than
      demyelinating injury. Hence, even if NCSs yield normal findings, peripheral
      nerves may be damaged. F/U studies and opposite examinations are required for the
      exact evaluation of peripheral nerve damage. 

PMID- 23877151
TI  - In situ template generation via N-alkylation in the syntheses of open-framework
      zinc phosphites and phosphate.
AB  - In methanol-aqueous solutions, three novel structure-directing agents (SDAs) were
      generated in situ and presented. These in situ reactions feature N-methylation
      transformations between CH3OH solvent and organic cyclic aliphatic and aromatic
      amines, i.e. 2-methylpiperazine, 1,4-diazabicyclo[2,2,2]octane (dabco) and 3
      (aminomethyl)pyridine. Distinct from conventional Eschweiler-Clarke methylation
      containing excess formic acid and formaldehyde, such a direct methylation
      transformation from methanol molecules is unique. In the presence of new SDAs,
      three organically templated zinc phosphites/phosphates, [pmpip][Zn3(HPO3)4] I
      (pmpip = N,N,N',N'-tetramethyl-2-methylpiperazinium), [dmdabco][Zn3(HPO3)4] II
      (dmdabco = N,N'-dimethyl-1,4-diazabicyclo[2,2,2]octane) and [Hmampy][Zn2(HPO4)3]
      III (mampy = N-methyl-3-(aminomethyl)pyridine), have been prepared and
      structurally characterized by elemental analysis, IR, thermogravimetric analysis,
      powder and single-crystal X-ray diffraction. Compound I exhibits a 2D layer with
      eight-membered apertures, compounds II and III possess a 3D interrupted framework
      with intersecting 8-, 10- and 12-ring channels (for II), and 8-, 10-ring channels
      (for III), respectively. 

PMID- 23877149
TI  - Nilotinib-induced interstitial lung disease.
AB  - Nilotinib is a second-generation tyrosine kinase inhibitor active in patients
      with chronic myeloid leukemia (CML) resistant to imatinib, and has been recently
      approved for newly diagnosed patients. We present a case of nilotinib-induced
      interstitial lung disease (ILD). A 67-year-old female patient was initially
      treated with imatinib for chronic-phase Philadelphia chromosome-positive (Ph(+))
      CML. Imatinib was replaced by nilotinib because of hematological toxicity. The
      patient had received nilotinib for about 3 years without significant adverse
      effects. She visited the clinic due to chronic cough; chest X-ray revealed
      consolidations in both lung fields. Nilotinib-induced ILD was diagnosed based on
      intensive workup, including lung biopsy. She responded dramatically to
      corticosteroid therapy. To our knowledge, this is the first reported case of
      nilotinib-induced ILD in a patient with Ph(+) CML. We emphasize that if
      unexplained lung abnormalities progress in patients receiving nilotinib,
      physicians should consider this potentially fatal complication in their
      differential diagnoses. 

PMID- 23877150
TI  - Combination of high-dose melphalan and bortezomib as conditioning regimen for
      autologous peripheral blood stem cell transplantation in multiple myeloma.
AB  - Bortezomib and melphalan have synergistic effects against multiple myeloma (MM)
      cells. We conducted a pilot study on the combination of bortezomib and high-dose
      melphalan (Bor-HDM) as a conditioning regimen followed by autologous stem cell
      transplant (ASCT) in 17 Japanese patients with newly diagnosed MM, in comparison
      with a historical control of patients who received high-dose melphalan (HDM) only
      followed by ASCT. Nine patients received a single dose of bortezomib 1.3 mg/m(2)
      on day -1 in combination with melphalan 100 mg/m(2) on days -3 and -2 (Bor1-HDM),
      and eight received two doses of bortezomib 1.3 mg/m(2) on days -4 and -1 (Bor2
      HDM) in combination with HDM. Engraftment of autologous peripheral blood stem
      cells and regimen-related toxicities (RRT) were comparable among the HDM and Bor
      HDM groups. Probability of upgrading from a less than very good partial response
      (VGPR) to VGPR after ASCT was approximately two times higher in the Bor-HDM group
      than in the HDM group. However, we observed no significant differences in
      engraftment, RRT, and response rates between the Bor1-HDM and Bor2-HDM groups.
      The present study showed that concurrent administration of at least two doses of
      bortezomib in combination with HDM can be safe in Japanese patients. Additional
      large prospective randomized trials are required to address the optimal dosages
      and schedules of bortezomib administration, as well as the efficacy of the Bor
      HDM conditioning regimen for ASCT. 

PMID- 23877153
TI  - [Dose distribution from kV-cone beam computed tomography in image-guided
      radiotherapy].
AB  - Image-guided radiotherapy (IGRT) is an increasingly commonly adopted technique.
      As a result, however, total patient dose is increasing rapidly, especially when
      kV-cone beam computed tomography (CBCT) is applied. This study investigated the
      dosimetry of kV-CBCT using a Farmer ionization chamber with a (60)Co absorbed
      dose calibration factor. The absorbed-dose measurements were performed using an
      I'mRT phantom (RW3, IBA) which is employed for dose verification of intensity
      modulated radiotherapy (IMRT). The I'mRT phantom was used as a substitute for
      head and pelvis phantoms. The kV-CBCT absorbed dose was evaluated from a beam
      quality conversion factor of kV to (60)Co and the ionization ratio of the I'mRT
      phantom and water, calculated using the Monte Carlo method. The dose distribution
      in the I'mRT phantom was also measured using a radiophotoluminescent glass
      dosimeter (RGD). The absorbed doses for the pelvis phantom (full scan) ranged
      from 2.5-4 cGy for kV-CBCT and 4-8 cGy for MV-CBCT. TomoTherapy resulted in a
      lower dose of approximately 1.3 cGy due to fan-beam. For the head phantom (half
      scan), the doses ranged from 0.1-0.7 cGy for kV-CBCT and 3-5 cGy for MVCBCT. The
      results for RGD were similar to ion chamber measurements. It is necessary to
      decrease the absorbed dose of the organs at risk every time IGRT is applied. 

PMID- 23877152
TI  - Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial
      cells harboring mutated H-ras by inhibiting MMP-2 expression.
AB  - Metastasis is one of the most threatening features of the oncogenic process and
      the main cause of cancer-related mortality. Several studies have demonstrated
      that matrix metalloproteinases (MMPs) are critical for tumor invasion and
      metastasis. Resveratrol (3,5,4'-trihydroxystilbene), a phenolic compound of red
      wine, has been reported to be a natural chemopreventive agent. However, the
      cancer preventive effects of piceatannol (3,5,3',4'-tetrahydroxystilbene), a
      metabolite of resveratrol and the underlying molecular mechanisms have not yet
      been fully elucidated. In this study, we report that piceatannol inhi-bits H-ras
      induced MMP-2 activity and the invasive phenotype of MCF10A human breast
      epithelial cells harboring mutated H-ras (H-ras MCF10A cells) more effectively
      than resveratrol. Piceatannol attenuated the H-ras-induced phosphorylation of Akt
      in a time- and dose-dependent manner, whereas resveratrol, at the same
      concentrations, did not exert an inhibitory effect. In vitro kinase assays
      demonstrated that piceatannol significantly inhibited phosphatidylinositol 3
      kinase (PI3K) activity and suppressed phospha-tidylinositol (3,4,5)-trisphosphate
      (PIP3) expression in the H-ras MCF10A cells. Ex vivo pull-down assays revealed
      that piceatannol directly bound to PI3K, inhibiting PI3K activity. Data from
      molecular docking suggested that piceatannol is a more tight-binding inhibitor
      than resveratrol due to the additional hydrogen bond between the hydroxyl group
      and the backbone amide group of Val882 in the ATP-binding pocket of PI3K.

PMID- 23877154
TI  - [A comparison of four commercial radiation treatment planning systems for
      prostate intensity modulated radiation therapy].
AB  - At present, every manufacturer of intensity modulated radiation therapy (IMRT)
      equipment uses multi-leaf collimators (MLCs); however, each company's intensity
      modulation methods and dose calculation algorithms differ. This study used four
      typical radiation treatment planning systems (RTPSs) employed domestically for
      prostate IMRT plans to carry out 15 case studies by one planner based on the dose
      limits at this clinic. The results were used to compare the differences, if any,
      in RTPS treatment plans. With prostate IMRT plans, an overlap area exists between
      the PTV and the rectum. For this reason, while observing dose limits of 60-75 Gy
      (within the dose tolerated by the rectum), securing uniformity and concentration
      of dose is essential to create the most appropriate treatment plan for the PTV
      and other targets. Although each RTPS uses different planning methods, it was
      generally possible to observe this clinic's dose limits by adjusting the
      parameter values. When identical beam data is used, it is possible to create
      similar treatment plans. 

PMID- 23877155
TI  - [Design and study of parallel computing environment of Monte Carlo simulation for
      particle therapy planning using a public cloud-computing infrastructure].
AB  - This report was aimed at structuring the design of architectures and studying
      performance measurement of a parallel computing environment using a Monte Carlo
      simulation for particle therapy using a high performance computing (HPC) instance
      within a public cloud-computing infrastructure. Performance measurements showed
      an approximately 28 times faster speed than seen with single-thread architecture,
      combined with improved stability. A study of methods of optimizing the system
      operations also indicated lower cost. 

PMID- 23877156
TI  - [Physical characterizations for an integrated 160-leaf multi-leaf collimator with
      a new concept design].
AB  - In this article, we present a physical characterization of the agility(TM)
      (Elekta). agility(TM) is composed of 160 interdigitating multileaf collimators
      (MLCs) with a width of 5 mm at the isocenter. The physical characterizations that
      include leaf position accuracy, leakage, field penumbra and the tongue-and-groove
      (T&G) effect were evaluated using well-commissioned 4, 6 and 10-MV photon beams.
      The leaf position accuracy was within 0.5 mm for all gantry angles and each MLC.
      The leakage was 0.44% on average and reached 0.47% at 10 MV: remarkably low due
      to a new design with tilted leaves. However, the T&G effect occurred due to tilt.
      It was approximately 20.8% on average and reached 22.3% at 6 MV. The penumbra
      width increased up to 8.5 mm at a field size of 20*20 cm at 4 MV. High position
      designed MLCs create a wider penumbra but show lower leakage and large head
      clearance. Head clearance is an important factor in stereotactic radiotherapy
      with multiple non-coplanar beams. 

PMID- 23877157
TI  - [Assessment of left ventricular function using (201)Tl electrocardiogram-gated
      myocardial single photon emission computed tomography].
AB  - PURPOSE: Advances in computed tomography (CT) technology make it possible to
      obtain left ventricular wall motion using 3D reconstruction. In this study, we
      compared the images obtained from CT and (201)Tl electrocardiogram (ECG) gated
      single photon emission computed tomography (SPECT). METHODS: In 20 patients with
      ischemic heart disease, we performed (201)Tl ECG gated SPECT (GE Healthcare
      Millennium VG) and ECG gated CT (Philips Medical Systems Brilliance iCT) to
      evaluate of left ventricular wall motion during the resting phase. In SPECT, left
      ventricular images were reconstructed using quantitative gated SPECT (QGS)
      software. In CT, the images were reconstructed using Virtual Place (AZE
      Software). The left ventricle was classified into five regions (anterior,
      lateral, inferior, septal, and apical). The amplitude of the wall motion was
      classified into five grades according to AHA classification. The values of the
      wall motion were separately checked by two radiographers. RESULTS: Assessment of
      left ventricular function myocardial wall movement using the three-dimensional
      movie display with ECG gated myocardial SPECT data was in agreement with the
      evaluation by cardiac CT inspection, and corresponded with wall motion in 88 of
      all 100 segments. CONCLUSIONS: SPECT analysis has the same quantity as that of
      obtained from CT for evaluation of left ventricular wall motion.

PMID- 23877158
TI  - [Effect of Kiken-Yochi training (KYT) induction on patient safety at the
      department of radiological technology].
AB  - PURPOSE: In this report, we evaluated whether radiological technologists' (RTs')
      awareness of patient safety would improve and what kind of effects would be seen
      at the department of radiological technology by introducing KYT [K: kiken
      (hazard), Y: yochi (prediction), T: (training)]. METHODS: KYT was carried out by
      ten RTs based on a KYT sheet for the department of radiological technology. To
      evaluate the effects of KYT, we asked nine questions each to ten participants
      before and after KYT enforcement with regard to their attitude to patient safety
      and to operating procedures for working safely. RESULTS: Significant improvements
      after KYT enforcement were obtained in two items concerning medical safety: It is
      important for any risk to be considered by more than one person; The interest in
      preventive measures against medical accident degree conducted now) and one
      concerning operating procedures (It is necessary to have a nurse assist during
      testing with the mobile X-ray apparatus) (p<0.05). CONCLUSIONS: Performing KYT
      resulted in improved awareness of the importance of patient safety. KYT also
      enabled medical staffers to evaluate objectively whether the medical safety
      measures currently performed would be effective for patients.

PMID- 23877159
TI  - Exposure dose and personal dosimeter.

PMID- 23877160
TI  - [Comparing multiple groups with continuous data--two-way Analysis of Variance].

PMID- 23877161
TI  - [The three-dimensional computer graphics in radiotherapy].

PMID- 23877162
TI  - [Diagnosis of ischemic heart disease. (1) Electrocardiogram (ECG)].

PMID- 23877163
TI  - [Report on controlling "medical" software].

PMID- 23877165
TI  - Interactions of iron-oxide filled carbon nanotubes with gas molecules.
AB  - This work presents a study on iron-oxide filled carbon nanotubes (CNTs) and their
      interaction with the surrounding atmosphere. Theoretical and experimental methods
      were employed to determine the interaction mechanism between the CNTs and some
      gases, such as O2 and N2. The electrical behavior of these CNTs under different
      atmospheric conditions was studied through resistance measurements, and for
      comparison, similar studies were conducted on non-filled carbon nanotubes. The
      iron-oxide filled CNTs were found to be more sensitive to the presence of O2 than
      the non-filled carbon nanotubes. This behavior was confirmed by the first
      principles simulations based on density functional theory with local spin density
      approximations for CNTs filled with hematite and magnetite iron-oxides. The
      theoretical study on the interactions of iron-oxide filled CNTs with gas
      molecules demonstrated a physisorption regime between the nanotube and the
      surrounding atmosphere, resulting in modifications of the electronic properties
      of this material. 

PMID- 23877166
TI  - Conversion from dose-to-graphite to dose-to-water in an 80 MeV/A carbon ion beam.
AB  - Based on experiments and numerical simulations, a study is carried out pertaining
      to the conversion of dose-to-graphite to dose-to-water in a carbon ion beam. This
      conversion is needed to establish graphite calorimeters as primary standards of
      absorbed dose in these beams. It is governed by the water-to-graphite mass
      collision stopping power ratio and fluence correction factors, which depend on
      the particle fluence distributions in each of the two media. The paper focuses on
      the experimental and numerical determination of this fluence correction factor
      for an 80 MeV/A carbon ion beam. Measurements have been performed in the nuclear
      physics laboratory INFN-LNS in Catania (Sicily, Italy). The numerical simulations
      have been made with a Geant4 Monte Carlo code through the GATE simulation
      platform. The experimental data are in good agreement with the simulated results
      for the fluence correction factors and are found to be close to unity. The
      experimental values increase with depth reaching 1.010 before the Bragg peak
      region. They have been determined with an uncertainty of 0.25%. Different
      numerical results are obtained depending on the level of approximation made in
      calculating the fluence correction factors. When considering carbon ions only,
      the difference between measured and calculated values is maximal just before the
      Bragg peak, but its value is less than 1.005. The numerical value is close to
      unity at the surface and increases to 1.005 near the Bragg peak. When the fluence
      of all charged particles is considered, the fluence correction factors are lower
      than unity at the surface and increase with depth up to 1.025 before the Bragg
      peak. Besides carbon ions, secondary particles created due to nuclear
      interactions have to be included in the analysis: boron ions ((10)B and (11)B),
      beryllium ions ((7)Be), alpha particles and protons. At the conclusion of this
      work, we have the conversion of dose-to-graphite to dose-to-water to apply to the
      response of a graphite calorimeter in an 80 MeV/A carbon ion beam. This
      conversion consists of the product of two contributions: the water-to-graphite
      electronic mass collision stopping power ratio, which is equal to 1.115, and the
      fluence correction factor which varies linearly with depth, as k(fl, all) =
      0.9995 + 0.0048(zw-eq). The latter has been determined on the basis of
      experiments and numerical simulations.

PMID- 23877167
TI  - We cannot cure ataxia,we can only eradicate it.

PMID- 23877168
TI  - In-situ ultra-sensitive infrared absorption spectroscopy of biomolecule
      interactions in real time with plasmonic nanoantennas.
AB  - Infrared absorption spectroscopy is a powerful biochemical analysis tool as it
      extracts detailed molecular structural information in a label-free fashion. Its
      molecular specificity renders the technique sensitive to the subtle
      conformational changes exhibited by proteins in response to a variety of stimuli.
      Yet, sensitivity limitations and the extremely strong absorption bands of liquid
      water severely limit infrared spectroscopy in performing kinetic measurements in
      biomolecules' native, aqueous environments. Here we demonstrate a plasmonic chip
      based technology that overcomes these challenges, enabling the in-situ monitoring
      of protein and nanoparticle interactions at high sensitivity in real time, even
      allowing the observation of minute volumes of water displacement during binding
      events. Our approach leverages the plasmonic enhancement of absorption bands in
      conjunction with a non-classical form of internal reflection. These features not
      only expand the reach of infrared spectroscopy to a new class of biological
      interactions but also additionally enable a unique chip-based technology. 

PMID- 23877169
TI  - Plasmonic enhancement of visible-light water splitting with Au-TiO2 composite
      aerogels.
AB  - We demonstrate plasmonic enhancement of visible-light-driven splitting of water
      at three-dimensionally (3D) networked gold-titania (Au-TiO2) aerogels. The sol
      gel-derived ultraporous composite nanoarchitecture, which contains 1 to 8.5 wt%
      Au nanoparticles and titania in the anatase form, retains the high surface area
      and mesoporosity of unmodified TiO2 aerogels and maintains stable dispersion of
      the ~5 nm Au guests. A broad surface plasmon resonance (SPR) feature centered at
      ~550 nm is present for the Au-TiO2 aerogels, but not Au-free TiO2 aerogels, and
      spans a wide range of the visible spectrum. Gold-derived SPR in Au-TiO2 aerogels
      cast as films on transparent electrodes drives photoelectrochemical oxidation of
      aqueous hydroxide and extends the photocatalytic activity of TiO2 from the
      ultraviolet region to visible wavelengths exceeding 700 nm. Films of Au-TiO2
      aerogels in which Au nanoparticles are deposited on pre-formed TiO2 aerogels by a
      deposition-precipitation method (DP Au/TiO2) also photoelectrochemically oxidize
      aqueous hydroxide, but less efficiently than 3D Au-TiO2, despite having an
      essentially identical Au nanoparticle weight fraction and size distribution. For
      example, 3D Au-TiO2 containing 1 wt% Au is as active as DP Au/TiO2 with 4 wt% Au.
      The higher photocatalytic activity of 3D Au-TiO2 derives only in part from its
      ability to retain the surface area and porosity of unmodified TiO2 aerogel. The
      magnitude of improvement indicates that in the 3D arrangement either a more
      accessible photoelectrochemical reaction interphase (three-phase boundary) exists
      or more efficient conversion of excited surface plasmons into charge carriers
      occurs, thereby amplifying reactivity over DP Au/TiO2. The difference in
      photocatalytic efficiency between the two forms of Au-TiO2 demonstrates the
      importance of defining the structure of Au[parallel]TiO2 interfaces within
      catalytic Au-TiO2 nanoarchitectures.

PMID- 23877170
TI  - Short-term functional outcomes of first metatarsophalangeal total joint
      replacement for hallux rigidus.
AB  - BACKGROUND: Although metatarsophalangeal (MTP) arthrodesis has been advocated by
      many authors, implant arthroplasty appears to be successful option in advanced
      hallux rigidus (HR). The aim of our study was to evaluate the early results of
      the ToeFit-Plus prosthesis for the treatment of HR. METHODS: Between December
      2007 and January 2011, a total of 26 toes of 24 patients with MTP arthritis of
      the great toe were treated with ToeFit-Plus implant. The average follow-up time
      was 29.9 (range: 25 to 62) months. All patients were evaluated clinically and
      radiographically. Postoperative satisfaction and function were scored according
      to the American Orthopaedic Foot and Ankle Society (AOFAS) score. Pain was
      assessed with the use of a visual analogue scale. RESULTS: Mean preoperative
      AOFAS score improved from 42.7 (range: 36 to 59) to 88.5 (range: 59 to 98) at the
      final follow-up (P < .01). Preoperative average visual analogue scale pain scores
      improved from 7.4 preoperatively to 1.9 at the final follow-up (P < .01). The
      average MTP joint range of motion improved from 25.9 degrees preoperatively to
      53.8 degrees at the final follow-up. No radiologic loosening was found, but
      radiolucency was observed in 2 patients with this implant. No revision was
      required for any of the patients during the follow-up period. CONCLUSIONS: This
      total first MTP joint prosthesis yielded good functional outcome and high patient
      satisfaction level with low early complication rate. Preservation of joint
      movement and good pain relief with early mobilization were the advantages of this
      procedure. Salvage arthrodesis remains an option if future revisions are
      indicated. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 23877172
TI  - Profiling and sequence analysis of gangliosides in human astrocytoma by high
      resolution mass spectrometry.
AB  - In this preliminary investigation, a low-grade astrocytoma (AcT) is investigated
      by high-resolution (HR) mass spectrometry (MS) aiming at characterization of
      gangliosides with potential biomarker value. The research was conducted towards a
      comparative mapping of ganglioside expression in AcT, its surrounding tissue (ST)
      and a normal control brain tissue (NT). HR MS was conducted in the negative ion
      mode nanoelectrospray ionization (nanoESI). Fragmentation analysis was carried
      out by collision-induced dissociation (CID) MS(2)-MS(4.) Due to the high
      resolving power and mass accuracy, by comparative mapping of the ganglioside
      extracts from AcT, ST and NT, under identical conditions, 37 different species in
      AcT, 40 in ST and 56 in NT were identified. AcT and ST were found to contain 18
      identical ganglioside components. Among all three specimens, ST extract presented
      the highest levels of sialylation, fucosylation and acetylation, a feature which
      might be correlated to the tumor expansion in the adjacent brain area. MS mapping
      indicated also that AcT, ST and NT share one doubly deprotonated molecule at m/z
      1063.31, attributable to GT1(d18:1/18:0) or GT1(d18:0/18:1). CID MS(2)-MS(4) on
      these particular ions detected in AcT and ST provided data supporting GT1c isomer
      in the investigated astrocytoma tissue. Our results show that HR MS has a
      remarkable potential in brain cancer research for the determination of tumor
      associated markers and for their structural determination. 

PMID- 23877173
TI  - High-resolution atmospheric pressure infrared laser desorption/ionization mass
      spectrometry imaging of biological tissue.
AB  - An atmospheric pressure laser desorption/ionization mass spectrometry imaging ion
      source has been developed that combines high spatial resolution and high mass
      resolution for the in situ analysis of biological tissue. The system is based on
      an infrared laser system working at 2.94 to 3.10 MUm wavelength, employing a
      Nd:YAG laser-pumped optical parametrical oscillator. A Raman-shifted Nd:YAG laser
      system was also tested as an alternative irradiation source. A dedicated optical
      setup was used to focus the laser beam, coaxially with the ion optical axis and
      normal to the sample surface, to a spot size of 30 MUm in diameter. No additional
      matrix was needed for laser desorption/ionization. A cooling stage was developed
      to reduce evaporation of physiological cell water. Ions were formed under
      atmospheric pressure and transferred by an extended heated capillary into the
      atmospheric pressure inlet of an orbital trapping mass spectrometer. Various
      phospholipid compounds were detected, identified, and imaged at a pixel
      resolution of up to 25 MUm from mouse brain tissue sections. Mass accuracies of
      better than 2 ppm and a mass resolution of 30,000 at m/z = 400 were achieved for
      these measurements.

PMID- 23877174
TI  - GC-MS analysis of cuticular lipids in recent and older scavenger insect puparia.
      An approach to estimate the postmortem interval (PMI).
AB  - An analytical method was developed to characterize puparia cuticular lipids
      (hydrocarbons, waxes) and to compare the molecular distribution patterns in the
      extracts from either recent or older puparia. Acid-catalyzed transesterification
      and solvent extraction and purification, followed by combined gas chromatography
      coupled to mass spectrometry, were optimized for the determination of
      hydrocarbons and fatty acid ethyl esters from transesterified waxes, extracted
      from a single species of a fly scavenger (Hydrotaea aenescens Wiedemann, 1830).
      Comparison between recent (2012) or older (1997) puparia contents has highlighted
      significant composition differences, in particular, a general decrease of the
      chain length in the n-alkane distribution pattern and, on the contrary, an
      increase of the ester chain length. Both extracts contain traces of three hopane
      hydrocarbon congeners. Preliminary results evidence the change in puparia lipid
      composition over time, thus potentially providing new indices for estimating
      postmortem interval. 

PMID- 23877171
TI  - Thymus and aging: morphological, radiological, and functional overview.
AB  - Aging is a continuous process that induces many alterations in the
      cytoarchitecture of different organs and systems both in humans and animals.
      Moreover, it is associated with increased susceptibility to infectious,
      autoimmune, and neoplastic processes. The thymus is a primary lymphoid organ
      responsible for the production of immunocompetent T cells and, with aging, it
      atrophies and declines in functions. Universality of thymic involution in all
      species possessing thymus, including human, indicates it as a long-standing
      evolutionary event. Although it is accepted that many factors contribute to age
      associated thymic involution, little is known about the mechanisms involved in
      the process. The exact time point of the initiation is not well defined. To
      address the issue, we report the exact age of thymus throughout the review so
      that readers can have a nicely pictured synoptic view of the process. Focusing
      our attention on the different stages of the development of the thymus gland
      (natal, postnatal, adult, and old), we describe chronologically the morphological
      changes of the gland. We report that the thymic morphology and cell types are
      evolutionarily preserved in several vertebrate species. This finding is important
      in understanding the similar problems caused by senescence and other diseases.
      Another point that we considered very important is to indicate the assessment of
      the thymus through radiological images to highlight its variability in shape,
      size, and anatomical conformation. 

PMID- 23877176
TI  - Rapid and sensitive HILIC-MS/MS analysis of carnitine and acetylcarnitine in
      biological fluids.
AB  - Monitoring carnitine and acetylcarnitine levels in biological fluids is a
      powerful tool for diagnostic studies. Research has recently shown that the
      analysis of carnitine and related compounds in clinical samples can be
      accomplished by different analytical approaches. Because of the polar and ionic
      nature of the analytes and matrix complexity, accurate quantitation is a highly
      challenging task. Thus, sample processing factors, preparation/cleanup
      procedures, and chromatographic/ionization/detection parameters were evaluated.
      On the basis of the results obtained, a rapid, selective, sensitive method based
      on hydrophilic interaction liquid chromatography-tandem mass spectrometry for the
      analysis of carnitine and acetylcarnitine in serum and urine samples is proposed.
      The matrix effect was assessed. The proposed approach was validated, the limits
      of detection were in the nanomolar range, and carnitine and acetylcarnitine
      levels were found within the micromolar range in both types of sample. 

PMID- 23877175
TI  - Differences in the hippocampal frequency of creatine inclusions between the acute
      and latent phases of pilocarpine model defined using synchrotron radiation-based
      FTIR microspectroscopy.
AB  - Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. Of
      the animal models developed to investigate the pathogenesis of TLE, the one with
      pilocarpine-induced seizures is most often used. After pilocarpine administration
      in animals, three distinct periods--acute, latent, and chronic--can be
      distinguished according to their behavior. The present paper is the continuation
      of our previous study which has shown an increased occurrence of creatine
      inclusions in rat hippocampal formations from the acute phase of pilocarpine
      induced status epilepticus (SE) and positive correlation between their quantity
      and the total time of seizure activity within the observation period. In this
      paper, we tried to verify if anomalies in hippocampal creatine accumulation were
      the temporary or permanent effect of pilocarpine-evoked seizures. To realize this
      purpose, male Wistar rats in the latent phase (3 days after pilocarpine
      administration) were examined. The results obtained for the period when
      stabilization of animal behavior and EEG occurs were afterwards compared with
      ones obtained for the acute phase of pilocarpine-induced SE and for naive
      controls. To investigate the frequency of creatine inclusions within the
      hippocampal formation as well as in its selected areas (sectors 1-3 of Ammon's
      horn (CA1-CA3), dentate gyrus (DG), and hilus of DG) and cellular layers
      (pyramidal, molecular, multiform, and granular cell layers), synchrotron
      radiation-based Fourier-transform infrared microspectroscopy was used. The
      applied technique, being a combination of light microscopy and infrared
      spectroscopy, allowed us to localize microscopic details in the analyzed samples
      and provided information concerning their chemical composition. Moreover, the use
      of a synchrotron source of IR radiation allowed us to carry out the research at
      the diffraction-limited spatial resolution which, because of the typical size of
      creatine inclusions (from a few to dozens of micrometers), was necessary for our
      study. The comparison of epileptic animals in the latent phase with controls
      showed statistically significant increase in the number of creatine inclusions
      for most of the analyzed hippocampal regions, all examined cellular layers, as
      well as the whole hippocampal formation. Moreover, for the hilus of the DG and
      CA3 area, the number of creatine deposits was higher in the latent than in the
      acute phase after pilocarpine injection. In light of the obtained results, an
      anomaly in the hippocampal accumulation of creatine is the long-term effect of
      pilocarpine-evoked seizures, and the intensity of this phenomenon may increase
      with time passing from the primary injury.

PMID- 23877177
TI  - Widespread occurrence of polyhalogenated compounds in fat from kitchen hoods.
AB  - Food and contaminated indoor environments are the most relevant sources of human
      exposure to polyhalogenated chemicals. This study analyzed for the first time fat
      residues in kitchen hoods for contaminations with polyhalogenated compounds. A
      wide range of contaminants was detected in all kitchen hoods (n = 15) and most of
      them could be quantified. Between 0.2 and 18 MUg polyhalogenated chemicals/g fat
      were detected, with chlorinated paraffins being the most relevant contaminant
      group. Aside from the chlorinated paraffins, each kitchen hood fat sample showed
      a distinct fingerprint. A wide range of old and current-use brominated flame
      retardants were also detected in the samples. In addition to these contaminants
      originating from their use in indoor equipment, residues of organochlorine
      pesticides and semi-volatile halogenated natural products verified that cooking
      of food, accompanied with the release of contaminants from the heated food, was
      another relevant source of contamination. Re-analyses of two samples after 3
      months only resulted in small variations in contaminant pattern and
      concentrations. Therefore, fat from kitchen hoods is proposed as an easily
      accessible matrix to assess contamination of these hazardous polyhalogenated
      chemicals. 

PMID- 23877179
TI  - Temperature-dependent size exclusion chromatography for the in situ investigation
      of dynamic bonding/debonding reactions.
AB  - Polymers capable of dynamic bonding/debonding reactions are of great interest in
      modern day research. Potential applications can be found in the fields of self
      healing materials or printable networks. Since temperature is often used as a
      stimulus for triggering reversible bonding reactions, an analysis operating at
      elevated temperatures is very useful for the in situ investigation of the
      reaction mechanism, as unwanted side effects can be minimized when performing the
      analyses at the same temperature at which the reactions occur. A temperature
      dependent size exclusion chromatographic system (TD SEC) has been optimized for
      investigating the kinetics of retro Diels-Alder-based depolymerization of Diels
      Alder polymers. The changing molecular weight distribution of the analyzed
      polymers during depolymerization gives valuable quantitative information on the
      kinetics of the reactions. Adequate data interpretation methods were developed
      for the correct evaluation of the chromatograms. The results are confirmed by
      high-temperature dynamic light scattering, thermogravimetric analysis, and time
      resolved nuclear magnetic resonance spectroscopy at high temperatures. In
      addition, the SEC system and column material stability under application
      conditions were assessed using thermoanalysis methods, infrared spectroscopy,
      nitrogen physisorption, and scanning electron microscopy. The findings
      demonstrate that the system is stable and, thus, we can reliably characterize
      such dynamically bonding/debonding systems with TD SEC. 

PMID- 23877178
TI  - Quantification of moxifloxacin in urine using surface-enhanced Raman spectroscopy
      (SERS) and multivariate curve resolution on a nanostructured gold surface.
AB  - A simple procedure is proposed for the determination of the antibiotic
      moxifloxacin in urine using nanostructured gold as surface-enhanced Raman
      scattering signal enhancer. The standard addition method in conjunction to
      multivariate curve resolution-alternating least squares was applied to eliminate
      the matrix effect and to isolate the spectral contribution of the analyte. Even
      in the presence of unexpected interferences in the urinary media, it was possible
      to extract and quantify the analyte response, reaching, in this way, the so
      called second-order advantage from first-order data. Moreover, although a
      saturation phenomenon of the metallic surface was observed, the results of the
      proposed methodology presented important advantages such as high sensitivity and
      simpler experimental procedures. The moxifloxacin was determined at levels of
      0.70 and 1.50 MUg mL(-1) in urine diluted to 1.0% (corresponding to 70.0 and 150
      MUg mL(-1) in the original samples) with relative errors of 4.23 and 8.70%,
      respectively. The limit of detection (0.085 MUg mL(-1)) and limit of
      quantification (0.26 MUg mL(-1)) values indicated that the quantification can be
      accomplished in urine up to 24 h after the administration of a single 400-mg
      dose.

PMID- 23877180
TI  - Catalytic DNA-based fluorescence polarization chiral sensing platform for L
      histidine detection at trace level.
AB  - This paper reports a novel fluorescence polarization (FP) chiral sensor approach
      based on a catalytic DNA. This platform involves an enzyme module (E), which was
      able to trigger the L-histidine-dependent cleavage of an RNA phosphoester bond of
      a substrate domain (S), whereas it did not accept the D-enantiomer as cofactor.
      Two assay formats were proposed, based on bi- and unimolecular strategies. The
      bimolecular design was related to the use of separate E and fluorescently
      labelled S* sequences. The two oligonucleotide strands were pre-assembled via
      complementary regions at their extremities. As the result of the large molecular
      volume of the formed assembly, the S* probe displayed a high fluorescence
      anisotropy signal. Upon addition of the L-histidine, the DNAzyme cleaved the
      phosphoester bond of the S* component, leading to the loss of stem stability and
      the release of single-stranded products of lower size. This was accompanied by a
      significant decrease in the fluorescence anisotropy response. As a simpler
      alternative, the unimolecular design, where E and S sequences are linked together
      through a loop to form a single fluorescent probe E-S*, was also investigated. It
      was found that the unimolecular approach provided an improved FP response
      relative to the bimolecular one. Under optimized operating conditions, such a
      chiral sensing platform allowed the detection of as low as 0.05% of the L
      histidine enantiomer in a non-racemic mixture.

PMID- 23877182
TI  - Ambient desorption/ionization mass spectrometry using a liquid sampling
      atmospheric glow discharge (LS-APGD) ionization source.
AB  - A novel approach to ambient desorption/ionization mass spectrometry (ADI-MS) is
      described, based on a recently developed liquid sampling-atmospheric pressure
      glow discharge (LS-APGD) ionization source. The device is essentially unmodified
      relative to its implementation in elemental mass spectrometry, where the
      operational space is characterized by low operation power (<10 W) and low
      solution delivery rates (<50 MUL min(-1)). In this implementation, the plasma is
      produced between a Ni anode and an electrolytic liquid (1 M HNO3) cathode flowing
      through a glass capillary that is angled towards the sample surface, at a
      distance of ~2 mm away. Analyte species can be desorbed/ionized from neat
      solution residues and complex solid samples. The ADI-LS-APGD source is mounted
      onto the source interface of a Thermo Finnigan LCQ Advantage Max quadrupole ion
      trap mass spectrometer without modifications to the instrument faceplate or ion
      optics. Described here is the initial evaluation of the roles of source geometry
      and working parameters, including electrolytic solution composition and plasma
      current, on the response of caffeine residues, with preliminary limits of
      detection based on the relative standard deviation of the spectral background
      suggested to be on the 10-pg level. Demonstrative spectra are presented for green
      tea extracts and raw leaves, coffee beans, a dried (raw) tobacco leaf, an
      analgesic tablet, and paper currency. Versatility is further revealed through the
      determination of components in common cigarette smoke. In each case, the spectra
      are characterized by (M + H)(+) species of the expected constituents. The
      capacity for a single source to perform both in solution and particulate
      elemental analysis (as shown previously) and ADI of molecular species is unique
      in the realm of mass spectrometry.

PMID- 23877183
TI  - Synthesis, characterization, and detection of new oxandrolone metabolites as long
      term markers in sports drug testing.
AB  - The discovery and implementation of the long-term metabolite of metandienone,
      namely 17beta-hydroxymethyl-17alpha-methyl-18-norandrost-1,4,13-trien-3-one, to
      doping control resulted in hundreds of positive metandienone findings worldwide
      and impressively demonstrated that prolonged detection periods significantly
      increase the effectiveness of sports drug testing. For oxandrolone and other 17
      methyl steroids, analogs of this metabolite have already been described, but
      comprehensive characterization and pharmacokinetic data are still missing. In
      this report, the synthesis of the two epimeric oxandrolone metabolites-17beta
      hydroxymethyl-17alpha-methyl-18-nor-2-oxa-5alpha-androsta-13-en-3-one and 17alpha
      hydroxymethyl-17beta-methyl-18-nor-2-oxa-5alpha-androsta-13-en-3-one-using a
      fungus (Cunninghamella elegans) based protocol is presented. The reference
      material was fully characterized by liquid chromatography nuclear magnetic
      resonance spectroscopy and high resolution/high accuracy mass spectrometry. To
      ensure a specific and sensitive detection in athlete's urine, different
      analytical approaches were followed, such as liquid chromatography-tandem mass
      spectrometry (QqQ and Q-Orbitrap) and gas chromatography-tandem mass
      spectrometry, in order to detect and identify the new target analytes. The
      applied methods have demonstrated good specificity and no significant matrix
      interferences. Linearity (R(2) > 0.99) was tested, and precise results were
      obtained for the detection of the analytes (coefficient of variation <20%).
      Limits of detection (S/N) for confirmatory and screening analysis were estimated
      at 1 and 2 ng/mL of urine, respectively. The assay was applied to oxandrolone
      post-administration samples to obtain data on the excretion of the different
      oxandrolone metabolites. The studied specimens demonstrated significantly longer
      detection periods (up to 18 days) for the new oxandrolone metabolites compared to
      commonly targeted metabolites such as epioxandrolone or 18-nor-oxandrolone,
      presenting a promising approach to improve the fight against doping.

PMID- 23877184
TI  - Rapid detection in food and feed.

PMID- 23877189
TI  - Guest responsivity of a two-dimensional coordination polymer incorporating a
      cholesterol-based co-ligand.
AB  - To implement specific guest responsivity, a hydrophobic cholesterol-based co
      ligand, cholest-5-en-3-yl-4-isonicotinate (Cholpy), was incorporated into a two
      dimensional Hofmann-type Co(II)Ni(II) coordination polymer. The chemically
      programmed structure successfully demonstrated the unique guest response with
      remarkable chromatic changes.

PMID- 23877190
TI  - Functionalized heterocyclic scaffolds derived from Morita-Baylis-Hillman
      Acetates.
AB  - Five series of heterocycles with extraordinary structural diversity have been
      regiospecifically synthesized from the same Morita-Baylis-Hillman Acetates
      (MBHAs). All four potential electrophilic sites (alpha, beta, gamma, delta) of
      MBHAs are proved to be reactive.

PMID- 23877191
TI  - A novel TaqI polymorphism in the coding region of the ovine TNXB gene in the MHC
      class III region: morphostructural and physiological influences.
AB  - The tenascin-XB (TNXB) gene has antiadhesive effects, functions in matrix
      maturation in connective tissues, and localizes to the major histocompatibility
      complex class III region. We hypothesized that it may influence adaptive
      physiological response through an effect on blood vessel function. We identified
      a novel g.1324 A->G polymorphism at a TaqI recognition site in a 454 bp fragment
      of ovine TNXB and genotyped it in 150 Nigerian sheep using PCR-RFLP. The missense
      mutation changes glutamic acid (GAA) to glycine (GGA). Among SNP genotypes,
      significant differences (P < 0.05) were observed in body weight and fore cannon
      bone length. Interaction effects of breed, SNP genotype, and geographic location
      had a significant effect (P < 0.05) on chest girth. The SNP genotype was
      significantly (P < 0.05) associated with physiological traits of pulse rate and
      skin temperature. The observed effect of this novel polymorphism may be mediated
      through its role in connective tissue biology, requiring further association and
      functional studies. 

PMID- 23877192
TI  - Detection of new point mutations of BRCA1 and BRCA2 in breast cancer patients.
AB  - This study included 20 selected female patients with breast cancer, 30 of their
      female relatives (sisters and daughters), and 10 healthy females as a control
      group. Genomic DNA was extracted from peripheral blood lymphocytes of all the
      subjects, and the polymerase chain reaction was carried out using specific
      primers for BRCA1 (exons 2 and 8) and BRCA2 (exons 9, 11, and 21). The mutations
      were detected using a single-strand conformation polymorphism assay and
      heteroduplex analysis. Finally, the sample variants and their controls were
      sequenced. Mutations were detected in 44% of the study population, with 18% found
      in the BRCA1 gene and 26% attributed to BRCA2. Five sequence variants were
      identified, including two frameshift mutations, one nonsense mutation, and two
      missense mutations. Therefore, we conclude that germline mutations in two major
      genes, BRCA1 and BRCA2, may have an important influence on the predisposition and
      development of familial breast cancer. 

PMID- 23877193
TI  - Genetic profiles and prediction of the success of young athletes' transition from
      middle- to long-distance runs: an exploratory study.
AB  - The aim of the study was to assess whether an aerobic-favoring genetic profile
      can predict the success of a shift from middle- to long-distance running.
      Thirteen elite middle-distance runners were divided into successful and
      nonsuccessful groups in their shift toward long-distance runs. All the runners
      began their training program at the age of 14-15, and after 6-7 years, changed
      focus and adjusted their training program to fit longer running distances. The
      participants' personal records in the longer events were set at the age of 25-27,
      about 3-5 years after the training readjustment took place. The endurance genetic
      score based on 9 polymorphisms was computed as the endurance genetic distance
      score (EGDS9). The power genetic distance score (PGDS5) was computed based on 5
      power-related genetic polymorphisms. The mean EGDS9 was significantly higher
      among the successful group than the nonsuccessful group (37.1 and 23.3,
      respectively, p < .005, effect size 0.75), while the mean PGDS5 was not
      statistically different between the 2 groups (p = .13). Our findings suggest the
      possible use of genetic profiles as an added tool for determining appropriate
      competitive transition and specialization in young athletes involved in early
      phases of talent development. 

PMID- 23877194
TI  - Trajectories of Mexican American and mainstream cultural values among Mexican
      American adolescents.
AB  - Mexican Americans are one of the largest and fastest growing ethnic groups in the
      United States, yet we have limited knowledge regarding changes (i.e.,
      developmental trajectories) in cultural orientation based upon their exposure to
      the Mexican American and mainstream cultures. We examined the parallel
      trajectories of Mexican American and mainstream cultural values in a sample of
      749 Mexican American adolescents (49 % female) across assessments during the
      fifth grade (approximately 11 years of age), the seventh grade (approximately 13
      years of age) and the tenth grade (approximately 16 years of age). We expected
      that these values would change over this developmental period and this
      longitudinal approach is more appropriate than the often used median split
      classification to identify distinct types of acculturation. We found four
      distinct acculturation trajectory groups: two trajectory groups that were
      increasing slightly with age in the endorsement of mainstream cultural values,
      one of which was relatively stable in Mexican American cultural values while the
      other was declining in their endorsement of these values; and two trajectory
      groups that were declining substantially with age in their endorsement of
      mainstream cultural values, one of which was also declining in Mexican American
      cultural values and the other which was stable in these values. These four
      trajectory groups differed in expected ways on a number of theoretically related
      cultural variables, but were not highly consistent with the median split
      classifications. The findings highlight the need to utilize longitudinal data to
      examine the developmental changes of Mexican American individual's adaptation to
      the ethnic and mainstream culture in order to understand more fully the processes
      of acculturation and enculturation. 

PMID- 23877195
TI  - Differences in the regulation of ochratoxin A by the HOG pathway in Penicillium
      and Aspergillus in response to high osmolar environments.
AB  - Penicillium verrucosum, P. nordicum and Aspergillus carbonarius are three
      important ochratoxin A producing species. P. verrucosum is in addition able to
      produce citrinin. It has been shown earlier that P. nordicum is adapted to NaCl
      rich environments like salt rich dry cured foods or even salines. In this
      organism, the biosynthesis of ochratoxin A plays an adaptive role in this
      habitat. P. verrucosum generally can be found on cereals, but occasionally also
      on salt rich dry cured foods. In contrast A. carbonarius usually cannot be found
      in NaCl rich environments, but it occurs in another environment with high
      concentration of solutes, e.g., in sugar rich substrates like grapes and grape
      juices. Usually osmotic challenging conditions activate the HOG MAP kinase signal
      cascade, which in turn activates various osmo-regulated genes. In the current
      analysis, it could be demonstrated that in case of P. nordicum and P. verrucosum
      the NaCl induced production of ochratoxin A is correlated to the phosphorylation
      status of the HOG MAP kinase. Just the opposite was true for A. carbonarius. In
      this case, also higher amounts of NaCl in the medium lead to an increased
      phosphorylation status of HOG, but no increase in ochratoxin biosynthesis was
      observed. In contrast to the Penicillia, higher NaCl concentrations lead to a
      rapid cessation of growth by A. carbonarius. High glucose concentrations have
      much less impact on growth and the phosphorylation of HOG. 

PMID- 23877196
TI  - Development and evaluation of monoclonal antibodies for the glucoside of T-2
      toxin (t2-glc).
AB  - The interactions between fungi and plants can yield metabolites that are toxic in
      animal systems. Certain fungi are known to produce sesquiterpenoid
      trichothecenes, such as T-2 toxin, that are biotransformed by several mechanisms
      including glucosylation. The glucosylated forms have been found in grain and are
      of interest as potential reservoirs of T-2 toxin that are not detected by many
      analytical methods. Hence the glucosides of trichothecenes are often termed
      "masked" mycotoxins. The glucoside of T-2 toxin (T2-Glc) was linked to keyhole
      limpet hemocyanin and used to produce antibodies in mice. Ten monoclonal antibody
      (Mab)-producing hybridoma cell lines were developed. The Mabs were used in
      immunoassays to detect T2-Glc and T-2 toxin, with midpoints of inhibition curves
      (IC50s) in the low ng/mL range. Most of the Mabs demonstrated good cross
      reactivity to T-2 toxin, with lower recognition of HT-2 toxin. One of the clones
      (2-13) was further characterized with in-depth cross-reactivity and solvent
      tolerance studies. Results suggest Mab 2-13 will be useful for the simultaneous
      detection of T-2 toxin and T2-Glc. 

PMID- 23877197
TI  - Tailoring electronic states of a single molecule using adamantane-based molecular
      tripods.
AB  - Adsorption structures and electronic states of molecular tripods, having a Br
      atom (BATT) and a ferrocene derivative (Ferrocene-ATT) at the head part of the
      adamantane-based trithiolate, adsorbed on Au(111) have been investigated using
      low temperature scanning tunneling microscopy (STM) and scanning tunneling
      spectroscopy (STS). We found that BATT and Ferrocene-ATT form self-assembled
      monolayers (SAMs), and their orderings are identical to one another, which
      suggests that the adsorption structure of adamantane-based molecular tripods is
      independent of the type of functional substituent attached to the head part. The
      electronic states originated from the ferrocene group were confirmed in the STS
      spectrum of Ferrocene-ATT whereas those are absent in the BATT spectrum. We note
      that the ferrocene part has few interactions with the Au substrate owing not only
      to the upright geometry of Ferrocene-ATT but also to the insulative properties of
      the adamantane base. The STS mapping revealed the spatial distribution of the
      electronic state of Ferrocene-ATT. 

PMID- 23877198
TI  - Selegiline rescues gait deficits and the loss of dopaminergic neurons in a
      subacute MPTP mouse model of Parkinson's disease.
AB  - The monoamine oxidase type-B (MAO-B) inhibitor, selegiline, is often recommended
      as a first-line treatment for Parkinson's disease (PD) and has been shwon to
      possess neuroprotective effects. The aim of the present study was to determine
      whether selegiline increases the levels of the neurotrophic factors (NTFs), glial
      cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic
      factor (BDNF), and whether it rescues motor dysfunction and the loss of
      dopaminergic neurons in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP)-induced lesions. We found that the oral administration of selegiline (1.0
      mg/kg/day for 14 days) successfully suppressed the MPTP-induced reduction of
      nigral dopaminergic neurons and striatal fibers (192.68 and 162.76% of MPTP
      exposed animals, respectively; both P<0.001). Moreover, improvements in gait
      dysfunction were observed after 7 and 14 days of a low dose of selegiline that is
      reported not to inhibit MAO-B. Furthermore, there was a significant increase in
      GDNF and BDNF mRNA (2.10 and 2.75-fold) and protein levels (143.53 and 157.05%)
      in the selegiline-treated mice compared with the saline-treated MPTP-exposed
      mice. In addition, the Bax/Bcl-2 gene and protein expression ratios were
      significantly increased in the MPTP-exposed mice, and this effect was reversed by
      selegiline. Correlation analysis revealed that gait measurement and GDNF/BDNF
      levels positively correlated with the number of dopaminergic neurons. These
      findings demonstrate that selegiline has neurorescue effects that are possibly
      associated with the induction of NTFs and anti-apoptotic genes.

PMID- 23877199
TI  - Myeloid leukemia with t(7;21)(p22;q22) and 5q deletion.
AB  - The rare but recurrent RUNX1-USP42 fusion gene is the result of a
      t(7;21)(p22;q22) chromosomal translocation and has been described in 6 cases of
      acute myeloid leukemia (AML) and one case of refractory anemia with excess of
      blast. In the present study, we present the molecular genetic analysis and the
      clinical features of a t(7;21)(p22;q22)-positive AML case. PCR amplified two
      RUNX1-USP42 cDNA fragments but no reciprocal USP42-RUNX1 fragment indicating that
      the RUNX1-USP42 is the leukemogenic fusion gene. Sequencing of the two amplified
      fragments showed that exon 6 or exon 7 of RUNX1 (accession number NM_001754
      version 3) was fused to exon 3 of USP42 (accession number NM_032172 version 2).
      The predicted RUNX1-USP42 fusion protein would contain the Runt homology domain
      (RHD), which is responsible for heterodimerization with CBFB and for DNA binding,
      and the catalytic UCH (ubiquitin carboxyl terminal hydroxylase) domain of the
      USP42 protein. The bone marrow cells in the present case also had a 5q deletion,
      and it was revealed that 5 out of the 8 reported cases (including the present
      case) with t(7;21)(p22;q22)/RUNX1-USP42 also had cytogenetic abnormalities of 5q.
      The fact that t(7;21) and 5q- occur together much more often than chance would
      allow seems to be unquestionable, although the pathogenetic connection between
      the two aberrations remains unknown.

PMID- 23877200
TI  - Direct nitrogen fixation at the edges of graphene nanoplatelets as efficient
      electrocatalysts for energy conversion.
AB  - Nitrogen fixation is essential for the synthesis of many important chemicals
      (e.g., fertilizers, explosives) and basic building blocks for all forms of life
      (e.g., nucleotides for DNA and RNA, amino acids for proteins). However, direct
      nitrogen fixation is challenging as nitrogen (N2) does not easily react with
      other chemicals. By dry ball-milling graphite with N2, we have discovered a
      simple, but versatile, scalable and eco-friendly, approach to direct fixation of
      N2 at the edges of graphene nanoplatelets (GnPs). The mechanochemical cracking of
      graphitic C--C bonds generated active carbon species that react directly with N2
      to form five- and six-membered aromatic rings at the broken edges, leading to
      solution-processable edge-nitrogenated graphene nanoplatelets (NGnPs) with superb
      catalytic performance in both dye-sensitized solar cells and fuel cells to
      replace conventional Pt-based catalysts for energy conversion.

PMID- 23877201
TI  - Retail-based clinics: Public preferences and professional choices.

PMID- 23877203
TI  - Aortic valve replacement after previous coronary artery bypass grafting: a case
      report.
AB  - We experienced a case of aortic valve replacement after previous coronary artery
      bypass grafting with patent bypass grafts. Based on the retrosternal anatomy
      assessed by preoperative angiography and thoracic computed tomography, aortic
      valve replacement was performed through a median resternotomy. After careful
      dissection of the right side of the heart and the ascending aorta,
      cardiopulmonary bypass was established with cannulation of the ascending aorta
      and bicaval venous cannulation. The patent bypass grafts were dissected only as
      required for clamping and were clamped during cardiac arrest. After aortic valve
      replacement, the patient was uneventfully weaned from cardiopulmonary bypass and
      had a good postoperative recovery. It is important that surgeons have a
      meticulous strategy for reducing the risks associated with operating on patients
      with patent bypass grafts. We report on the surgical management of patients
      undergoing aortic valve replacement after previous coronary artery bypass
      grafting, including careful planning during the first operation. 

PMID- 23877202
TI  - Coronary flow reserve from mouse to man--from mechanistic understanding to future
      interventions.
AB  - Myocardial ischemia is recognized as an important mechanism increasing the risk
      for cardiovascular events in both symptomatic and asymptomatic patients. In
      addition to obstructive coronary diseases, systemic inflammation, macro- and
      microvascular function are additional important mechanisms contributing to the
      ischemic myocardium. Accumulating evidence indicates that coronary flow reserve
      (CFR) is a quantitative measurement of ischemia including integrated information
      on structure and function of the coronary artery at all levels. Not surprisingly,
      CFR has been shown to confer strong prognostic value for hard cardiovascular (CV)
      events in a number of relevant patient cohorts. Using high-resolution imaging, it
      is now possible to study coronary arteries from mouse to man. Therefore, CFR may
      be an important translational tool to risk-stratify patients and to perform both
      preclinical and clinical proof-of-concept studies before investing in large-scale
      outcome trials, thus improving the translational value for novel CV targets. 

PMID- 23877204
TI  - Voxel2MCNP: a framework for modeling, simulation and evaluation of radiation
      transport scenarios for Monte Carlo codes.
AB  - The basic idea of Voxel2MCNP is to provide a framework supporting users in
      modeling radiation transport scenarios using voxel phantoms and other geometric
      models, generating corresponding input for the Monte Carlo code MCNPX, and
      evaluating simulation output. Applications at Karlsruhe Institute of Technology
      are primarily whole and partial body counter calibration and calculation of dose
      conversion coefficients. A new generic data model describing data related to
      radiation transport, including phantom and detector geometries and their
      properties, sources, tallies and materials, has been developed. It is modular and
      generally independent of the targeted Monte Carlo code. The data model has been
      implemented as an XML-based file format to facilitate data exchange, and
      integrated with Voxel2MCNP to provide a common interface for modeling,
      visualization, and evaluation of data. Also, extensions to allow compatibility
      with several file formats, such as ENSDF for nuclear structure properties and
      radioactive decay data, SimpleGeo for solid geometry modeling, ImageJ for voxel
      lattices, and MCNPX's MCTAL for simulation results have been added. The framework
      is presented and discussed in this paper and example workflows for body counter
      calibration and calculation of dose conversion coefficients is given to
      illustrate its application. 

PMID- 23877205
TI  - Minimally invasive direct coronary artery bypass in the era of percutaneous
      coronary intervention.
AB  - AIM: Minimally invasive coronary artery bypass (MIDCAB) allows revascularization
      of the left anterior descending coronary (LAD) artery through a less traumatic
      surgical approach. However, the procedure is technically challenging and concern
      still exists, mainly based on graft patency. The purpose of this study is to
      critically evaluate short and long-term benefits of this surgical treatment.
      METHODS: Between June 1997 and July 2012, 306 patients underwent MIDCAB on LAD.
      The mean age was 62 +/- 10 years (range, 32-87 years) and 264 patients (86.3%)
      were men. Mean ejection fraction was 54%. Eighty-nine procedures (29.1%) were
      performed using a hybrid approach by means of MIDCAB and postoperative (60
      patients, 67.4%) or preoperative (29 patients, 32.6%) percutaneous interventions
      on non-LAD vessels. A EuroScore more than 6 was found in 43 (14%) patients. The
      average follow-up time was 9.5 +/- 3.2 years and was 89% complete. RESULTS: Six
      patients (1.9%) required intraoperative conversion to sternotomy, whereas
      cardiopulmonary bypass institution after the sternotomy was necessary in one.
      Postoperative acute myocardial infarction occurring nine patients (2.9%), low
      output syndrome in four (1.3%). Postoperative mortality was 1.6% (n = 5), and
      perioperative stroke rate 0.6% (n = 2). Five and 10-year survival were 94.1 and
      86.9%, respectively. Freedom from death due to cardiac events and major cardiac
      and cerebral events at 10 years was, respectively, 97.1 and 92.1%. CONCLUSIONS:
      The results confirm the favorable short and long-term results of the MIDCAB
      procedure. MIDCAB, in experienced centers, can represent an alternative treatment
      option for LAD disease.

PMID- 23877206
TI  - Oxidized low-density lipoprotein antibodies in myocardial infarction patients
      without classical risk factors.
AB  - AIM: To determine whether circulating antibodies against oxidized low-density
      lipoprotein (LDL; OLAB) levels are associated with acute myocardial infarction
      (AMI) in individuals without classical cardiovascular risk factors. METHODS: A
      case-control study including 34 first AMI patients without classical risk factors
      (smoking, dyslipidemia, hypertension or diabetes) and 45 population-based healthy
      controls. RESULTS: There were no differences in anthropometric variables between
      cases and controls. Oxidized LDL levels were similar in both groups. Total
      cholesterol, LDL cholesterol, apolipoprotein B and physical activity were lower
      in cases than in controls. OLAB levels were also lower in cases than controls
      (128 versus 447 U/l, P < 0.001). After adjusting for age, oxidized LDL and
      physical activity, participants with OLAB levels of 165 U/l or less had a higher
      risk of AMI (odds ratio, OR = 7.48, 95% confidence interval: 1.57-35.66). When
      the model was fitted with OLAB as a continuous variable, the natural logarithm
      (LnOLAB) levels were independently associated with AMI with an OR of 0.40 (95%
      confidence interval: 0.19-0.86). After adjusting the model by Framingham-risk
      adapted score and oxidized LDL, the LnOLAB levels maintained their independent
      association (OR of 0.43, 95% confidence interval: 0.23-0.79). CONCLUSION: First
      AMI patients without classical risk factors had lower levels of OLAB compared
      with healthy controls. It is likely that the immunological reaction due to
      oxidized LDL participates as a preventive factor in the physiopathology of
      atherosclerosis.

PMID- 23877207
TI  - Inaccuracy of available surgical risk scores to predict outcomes after
      transcatheter aortic valve replacement.
AB  - INTRODUCTION: Despite encouraging short-term and mid-term results, transcatheter
      aortic valve implantation (TAVI) interventions are still burdened from high rates
      of adverse events, stressing the need for accurate predictive risk instruments.
      We compared available surgical risk scores to describe unfavorable outcomes after
      TAVI. METHODS: The Age, Creatinine, and Ejection fraction (ACEF) score, the
      logistic Euroscore, and the Society of Thoracic Surgeons Mortality score (STS)
      were appraised for their independent power of prediction and for their accuracy
      (C-index) to predict 30-day and medium-term mortality, according to the Valve
      Academic Research Consortium. RESULTS: Nine hundred and sixty-two patients were
      included. All the scores demonstrated a moderate positive correlation. The
      closest correlation was observed between the STS score and Euroscore. After
      logistic regression analysis, STS score and Logistic Euroscore provided
      independent prediction for short-term all-cause mortality [P = 0.02, odds ratio
      (OR) 1.1; 95% confidence interval (CI) 1.06-1.31 and P = 0.027, OR 1.03; 95% CI
      1.01-1.405]. For in-hospital complications, only STS score performed
      significantly (P = 0.005, OR 1.05; 95% CI 1.01-1.06). ACEF, Euroscore, and STS
      score showed low accuracy for 30-day all-cause mortality (area under the curve
      0.6, 0.44-0.75; vs. 0.53, 0.42-0.61; vs. 0.62, 0.52-0.71, respectively), whereas
      STS score performed better for in-hospital complications (0.59, 0.55-0.64).
      Moreover, after Cox-multivariate adjustments, only ACEF score was near to
      significance to predict all-cause mortality at mid-term (OR 1.7; 0.8-2.9; P =
      0.058), showing the highest accuracy (0.63, 0.55-0.71). CONCLUSION: In TAVI
      patients, ACEF score, STS score and Logistic Euroscore provided only a moderate
      correlation and a low accuracy both for 30-day and medium-term outcomes.
      Dedicated scores are needed to properly tailor time and kind of approach.

PMID- 23877208
TI  - Persistent left superior vena cava associated with patent forame ovale: the value
      of an accidental diagnosis.

PMID- 23877209
TI  - [Role of 18F 2-fluoro-2-deoxyglucose positron emission tomography in upper
      gastrointestinal malignancies].
AB  - The 18F 2-fluoro-2-deoxyglucose (FDG) PET/CT scan is an imaging modality used in
      the management of patients with various types of malignancies. 18F-FDG PET/CT has
      demonstrated significant efficacy in the staging and detection of metastatic
      disease in malignancies of the gastrointestinal tract. The assessment of the
      metabolic response to chemotherapy and improvements of overall survivals in
      malignancies of esophagus and stomach has been demonstrated in several studies.
      This review focuses on the role of 18F-FDG PET/CT scan in staging, metastasis,
      predict of recurrence and assessment of metabolic response in malignancies of the
      upper gastrointestinal tract.

PMID- 23877210
TI  - Effect of Helicobacter pylori eradication on subsequent dysplasia development
      after endoscopic resection of gastric dysplasia.
AB  - BACKGROUND/AIMS: Eradication of Helicobacter pylori reduces the incidence of
      gastric cancer, and may inhibit gastric dysplasia progression into gastric
      cancer. The aim of this study was to investigate the effect of eradication of
      Helicobacter on the incidence of subsequent gastric dysplasia development after
      endoscopic resection. METHODS: Medical records of patients who underwent
      endoscopic resection for gastric dysplasia were retrospectively reviewed.
      Presence of H. pylori was assessed by the Campylobacter-like organism test and
      histology. The rate of subsequent dysplasia development after endoscopic
      resection between the eradication group and non-eradication group was compared.
      RESULTS: Total of 129 patients positive for H. pylori infection were included for
      analysis. Of these, 85 patients received successful eradication therapy and 44
      patients did not receive eradication therapy or failed to achieve successful
      eradication. Sex, mean age and pathologic grade of dysplasia did not differ
      between the two groups. In univariate analysis, the grade of intestinal
      metaplasia (p=0.013) significantly differed between metachronous dysplasia group
      and non-metachrounous dysplasia group. In multivariate analysis, eradication of
      H. pylori (p=0.014) was related to reduced incidence of subsequent gastric
      dysplasia development after endoscopic resection. CONCLUSIONS: Eradication of H.
      pylori likely has a beneficial effect in preventing the development of subsequent
      gastric dysplasia, a premalignant lesion of gastric cancer, after endoscopic
      resection.

PMID- 23877211
TI  - [The association between the therapeutic agent and the compliance of the patients
      with inflammatory bowel diseases].
AB  - BACKGROUND/AIMS: Adherence of the patients with inflammatory bowel diseases is
      important to maintain the remission. However, the patients do not always keep
      their appointments for treatment. The aim of this study was to investigate the
      clinical factors associated with adherence of patients in terms of appointment
      keeping. METHODS: A total of 73 subjects were retrospectively investigated from
      September 2005 to January 2012 at Dongguk University Ilsan Hospital (Goyang,
      Korea). We reviewed medical records including the age, sex, residence,
      medications, the disease activity, and the rate of keeping the date. A punctual
      visit was defined as outpatient visit on the scheduled date +/-7 days. Punctual
      patients for the visit were defined as their punctual visit rates exceed 90%.
      RESULTS: Male to female ratio was 2.4:1. Mean age was 41.5+/-15.4 years (range,
      20 to 78 years). Ulcerative colitis was 53 cases (72.6%) and Crohn's disease was
      20 cases (27.4%). Mean duration of disease was 42.0+/-41.6 months (range, 4 to
      226 months). Mean puntual visit rate was 86.7+/-16.0% (range, 27 to 100). Thirty
      eight patients (52.1%) were punctual patients for the visit. Azathioprine/6
      mercaptopurine treatment was associated with punctual patients for the visit (odd
      ratio, 3.19; 95% confidence interval, 1.12 to 9.09; p=0.03). However, other
      clinical factors did not influence the punctual visit rates. CONCLUSIONS: Our
      study demonstrated that the use of azathioprine/6-mercaptopurine was associated
      with keeping the appointment for meeting the doctor. Further prospective study
      would be necessary.

PMID- 23877212
TI  - [Is it useful to perform additional colonoscopy to detect unmatched lesion
      between positron emission tomography/computed tomography and colonoscopy?].
AB  - BACKGROUND/AIMS: Incidentally detected focal 18F-fluorodeoxyglucose (FDG) uptake
      was compared with colonoscopy. We investigated the characteristics of colon
      adenomas which were revealed on PET/CT. Then we identified whether additional
      colonoscopy was necessary in patients with lesions which were revealed on PET/CT
      but had no matched lesions on colonoscopy. METHODS: We retrospectively reviewed
      95 patients who underwent colonoscopy within a 6 month interval after they had
      focal FDG uptake from January 2010 to May 2012 at National Police Hospital in
      Korea. Also, we analyzed 30 patients who underwent additional colonoscopy within
      2 years after they had no matched lesions on primary colonoscopy. RESULTS: PET/CT
      depicted 54.6% (41/75) of adenomas and adenocarcinomas. The PET visibility of
      colon adenoma was significantly associated with degree of dysplasia (p=0.027),
      histologic type (p=0.040), and the size (p=0.038). The positivity rate was
      increased with higher degree of dysplasia (low-grade dysplasia, 47%; high-grade
      dysplasia, 78%; adenocarcinoma, 100%) and villous patterns of histologic type
      (tubular, 46.8%; tubulovillous, 87.5%; villous, 100%). Patients with adenomas
      larger than 10 mm (87.5%) had higher detection rate compared to those with
      adenomas smaller than 10 mm (49.0%). Among the 30 patients who underwent
      additional colonoscopy, only one patient had a 6 mm sized tubular adenoma (low
      grade dysplasia). CONCLUSIONS: Incidental focal colonic uptake may indicate
      advanced adenoma or adenocarcinoma. Thus, it justifies performing colonoscopy for
      identifying the presence of colon neoplasms. However, in case of unmatched
      lesions between PET/CT and colonoscopy, there was little evidence that additional
      colonoscopy would yield benefits.

PMID- 23877213
TI  - [A comparative study on serum immunoglobulin and tumor marker levels in the
      patients with autoimmune pancreatitis and pancreatobiliary malignancies].
AB  - BACKGROUND/AIMS: Autoimmune pancreatitis (AIP) often occurs with obstructive
      jaundice in old age in cases of weight loss, mimicking pancreatobiliary cancer.
      This study aimed to determine the sensitivity and specificity serum IgG, IgG4 and
      CEA, CA 19-9 levels for the diagnosis of AIP and their ability to distinguish AIP
      from pancreatobiliary cancer. METHODS: The level of serums IgG, IgG4 and CEA, CA
      19-9 were measured in 413 patients including 125 with AIP, 201 with pancreatic
      cancer, and 87 with cholangiocarcinoma. RESULTS: Among AIP patients, 43.2%
      (54/125) showed elevated IgG levels (>=1,800 mg/dL) and 52% (65/125) showed
      elevated IgG4 levels (>=135 mg/dL). Sensitivity and specificity of elevated serum
      IgG for diagnosis AIP were 43% and 88% respectively, and 52% and 97%,
      respectively for elevated serum IgG4. When the cut-off value of serum IgG4 was
      raised to 270 mg/dL (twice the upper limit of normal), the specificity improved
      to 100%. About 25% of the AIP patients showed an increased level of CA 19-9 at
      >37 U/mL and about 12.2% of them showed an increased level of CA 19-9 at >100
      U/mL. On the contrary, only 1.8% of the AIP patients showed an increased level of
      CEA at >6.0 ng/mL. CONCLUSIONS: To avoid unnecessary surgeries resulting from a
      misdiagnosed pancreatobiliary cancer as opposed to AIP, it is necessary to
      consider both serum immunoglobulin and tumor marker. In particular, because high
      level of IgG4 (>=270 mg/dL) and CA19-9 (>100 U/mL) are relatively rare in
      pancreatobiliary cancer and AIP, respectively, they will be helpful in
      differential diagnosis.

PMID- 23877214
TI  - A case of Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1 with
      urolithiasis as the initial presentation.
AB  - Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma and resultant
      hypergastrinemia, which leads to recurrent peptic ulcers. Because gastrinoma is
      the most common pancreatic endocrine tumor seen in multiple endocrine neoplasia
      type I (MEN 1), the possibility of gastrinoma should be investigated carefully
      when patients exhibit symptoms associated with hormonal changes. Ureteral stones
      associated with hyperparathyroidism in the early course of MEN 1 are known to be
      its most common clinical manifestation; appropriate evaluation and close follow
      up of patients with hypercalcemic urolithiasis can lead to an early diagnosis of
      gastrinoma. We report a patient with ZES associated with MEN 1, and urolithiasis
      as the presenting entity. A 51-year-old man visited the emergency department with
      recurrent epigastric pain. He had a history of calcium urinary stone 3 years ago,
      and 2 years later he had 2 operations for multiple jejunal ulcer perforations;
      these surgeries were 9 months apart. He was taking intermittent courses of
      antiulcer medication. Multiple peripancreatic nodular masses, a hepatic
      metastasis, parathyroid hyperplasia, and a pituitary microadenoma were confirmed
      by multimodal imaging studies. We diagnosed ZES with MEN 1 and performed
      sequential surgical excision of the gastrinomas and the parathyroid adenoma. The
      patient received octreotide injection therapy and close follow-up.

PMID- 23877215
TI  - [A case of celiac disease].
AB  - Celiac disease is a chronic absorptive disorder of the small intestine caused by
      gluten. The prevalence rate of celiac disease is 1% in Western countries. But, it
      is rare in Asian countries, and there is no celiac disease reported in Korea.
      Here, we report a case of celiac disease. An 36-years-old woman complained non
      specific abdominal pain and diarrhea. She had anemia and was taking medication
      for osteoporosis. Colonoscopy showed no abnormality except shallow ulcer at the
      terminal ileum. Gastroduodenoscopy showed micronodularity at the duodenum 2nd and
      3rd portion. Capsule endoscopy and enteroscopy showed villous atrophy and
      blunting of villi from the duodenum. Small intestinal pathology showed villous
      atrophy with lymphocyte infiltration. After gluten free diet, diarrhea, abdominal
      pain, anemia and osteoporosis were improved. And, she felt well-being sensation.
      This is a first case of celiac disease in Korea.

PMID- 23877216
TI  - [A case of primary aortoenteric fistula mimicking ulcer bleeding].
AB  - Primary aortoenteric fistula (PAEF) is a rare disease with a high mortality rate
      due to massive hemorrhaging and diagnostic difficulties. Although hemorrhagic
      regions can be identified by endoscopy, it is difficult to diagnose PAEF by this
      method. If PAEF is suspected, endoscopic procedure should be terminated and
      abdominal CT should be performed. Overlooking the herald bleeding of PAEF can
      lead to massive bleeding and death. An 85-year-old previously healthy male
      presented with a complaint of melena. Gastrointestinal endoscopy identified a
      hemorrhagic site in the third portion of the duodenum and endoscopic hemostasis
      was performed. However, during the procedure, it became apparent that the
      hemorrhage was probably not the result of a simple duodenal ulceration and
      abdominal CT was performed immediately. An aortic aneurysm connected to the
      duodenum was identified, confirming the diagnosis of PAEF. However, the patient
      died of massive hemorrhaging before an operation could be performed.

PMID- 23877217
TI  - [A case of pneumatosis intestinalis associated with sunitinib treatment for renal
      cell carcinoma].
AB  - Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor
      agents, approved by the United States Food and Drug Administration to use treat
      gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is
      known to commonly induce adverse reactions such as fatigue, nausea, diarrhea,
      stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output
      of left ventricle, and hypothyroidism. However, it has been reported to rarely
      induce adverse reactions such as nephrotic syndrome and irreversible reduction in
      renal functions, and cases of intestinal perforation or pneumatosis interstinalis
      as such reactions have been consistently reported. In this report, a 66-year old
      man showing abdominal pain had renal cell carcinoma and history of sunitinib at a
      dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the
      third cycle he was referred to the hospital because of abdominal pain. Computed
      tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his
      small bowel. The patient underwent surgical exploration that confirmed the
      pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare
      case of intestinal perforation with pneumatosis intestinalis after administration
      of sunitinib to a patient with metastatic renal cell carcinoma.

PMID- 23877218
TI  - Analytical probabilistic modeling for radiation therapy treatment planning.
AB  - This paper introduces the concept of analytical probabilistic modeling (APM) to
      quantify uncertainties in quality indicators of radiation therapy treatment
      plans. Assuming Gaussian probability densities over the input parameters of the
      treatment plan quality indicators, APM enables the calculation of the moments of
      the induced probability density over the treatment plan quality indicators by
      analytical integration. This paper focuses on analytical probabilistic dose
      calculation algorithms and the implications of APM regarding treatment planning.
      We derive closed-form expressions for the expectation value and the (co)variance
      of (1) intensity-modulated photon and proton dose distributions based on a pencil
      beam algorithm and (2) the standard quadratic objective function used in inverse
      planning. Complex correlation models of high dimensional uncertain input
      parameters and the different nature of random and systematic uncertainties in
      fractionated radiation therapy are explicitly incorporated into APM. APM variance
      calculations on phantom data sets show that the correlation assumptions and the
      difference of random and systematic uncertainties of the input parameters have a
      crucial impact on the uncertainty of the resulting dose. The derivations
      regarding the quadratic objective function show that APM has the potential to
      enable robust planning at almost the same computational cost like conventional
      inverse planning after a single probabilistic dose calculation. Beneficial
      applications of APM in the context of radiation therapy treatment planning are
      feasible. 

PMID- 23877219
TI  - A cationic and ferromagnetic hexametallic Mn(III) single-molecule magnet based on
      the salicylamidoxime ligand.
AB  - The salicylamidoxime-based complex [Mn6(MU3-O)2(H2N
      sao)6(py)6(EtOH)2](ClO4)2.4EtOH (1.4EtOH) constitutes the first example of a
      cationic and ferromagnetic member of the oxime-based family of [Mn(III)6] single
      molecule magnets. 

PMID- 23877220
TI  - Oximate metal complexes breaking the limiting esterolytic reactivity of oximate
      anions.
AB  - Zinc(II) and cadmium(II) complexes of a tridentate oximate ligand cleave 4
      nitrophenyl acetate with rate constants surpassing by two orders of magnitude
      those reported as the maximum possible level for highly basic free oximate anions
      as a result of removal of the "solvational imbalance" of the nucleophile by metal
      coordination.

PMID- 23877222
TI  - Multifunctional superparamagnetic iron oxide nanoparticles: design, synthesis and
      biomedical photonic applications.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) have shown great promise in
      biomedical applications. In this review, we summarize the recent advances in the
      design and fabrication of core-shell and hetero-structured SPIONs and further
      outline some exciting developments and progresses of these multifunctional SPIONs
      for diagnosis, multimodality imaging, therapy, and biophotonics. 

PMID- 23877221
TI  - Genome sequence and functional genomic analysis of the oil-degrading bacterium
      Oleispira antarctica.
AB  - Ubiquitous bacteria from the genus Oleispira drive oil degradation in the largest
      environment on Earth, the cold and deep sea. Here we report the genome sequence
      of Oleispira antarctica and show that compared with Alcanivorax borkumensis--the
      paradigm of mesophilic hydrocarbonoclastic bacteria--O. antarctica has a larger
      genome that has witnessed massive gene-transfer events. We identify an array of
      alkane monooxygenases, osmoprotectants, siderophores and micronutrient-scavenging
      pathways. We also show that at low temperatures, the main protein-folding machine
      Cpn60 functions as a single heptameric barrel that uses larger proteins as
      substrates compared with the classical double-barrel structure observed at higher
      temperatures. With 11 protein crystal structures, we further report the largest
      set of structures from one psychrotolerant organism. The most common structural
      feature is an increased content of surface-exposed negatively charged residues
      compared to their mesophilic counterparts. Our findings are relevant in the
      context of microbial cold-adaptation mechanisms and the development of strategies
      for oil-spill mitigation in cold environments.

PMID- 23877223
TI  - Characterization of a multidrug-resistant chronic myeloid leukemia cell line
      presenting multiple resistance mechanisms.
AB  - The multidrug-resistant (MDR) phenotype is multifactorial, and cell lines
      presenting multiple resistance mechanisms might be good models to understand the
      importance of the various pathways involved. The present work characterized a MDR
      chronic myeloid leukemia cell line, derived from K562 through a selective process
      using daunorubicin. This MDR cell line was shown to be resistant to vincristine,
      daunorubicin, and partially resistant to imatinib. It showed a slower duplication
      rate. Overexpression of ABCB1 and ABCC1 was observed at the protein and
      functional levels and the expression of CD95, a molecule related to cell death,
      was reduced in the MDR cell line. Conversely, no differences were observed
      related to the anti-apoptotic molecule Bcl-2 or p53 expression. The activation
      antigen CD69 was reduced in the MDR cell line and treatment with imatinib further
      decreased the expressed levels. Furthermore, secretion of IL-8 was diminished in
      the MDR cell line. When daunorubicin-selected cells were compared to another MDR
      cell line, Lucena 1, derived from the same parental line K562, and selected with
      vincristine, a different profile was observed in relation to most aspects
      studied. When both cell lines were silenced for ABCB1, differences in CD69 and
      CD95 were maintained, despite resistance reversal. These results reinforce the
      idea that cell lines selected in vitro may display multiple resistance strategies
      that may vary with the selective agent used as well as during different steps of
      the selection process.

PMID- 23877224
TI  - Genetic isolation of stem cell-derived pacemaker-nodal cardiac myocytes.
AB  - Dysfunction of the cardiac pacemaker tissues due to genetic defects, acquired
      diseases, or aging results in arrhythmias. When arrhythmias occur, artificial
      pacemaker implants are used for treatment. However, the numerous limitations of
      electronic implants have prompted studies of biological pacemakers that can
      integrate into the myocardium providing a permanent cure. Embryonic stem (ES)
      cells cultured as three-dimensional (3D) spheroid aggregates termed embryoid
      bodies possess the ability to generate all cardiac myocyte subtypes. Here, we
      report the use of a SHOX2 promoter and a Cx30.2 enhancer to genetically identify
      and isolate ES cell-derived sinoatrial node (SAN) and atrioventricular node (AVN)
      cells, respectively. The ES cell-derived Shox2 and Cx30.2 cardiac myocytes
      exhibit a spider cell morphology and high intracellular calcium loading
      characteristic of pacemaker-nodal myocytes. These cells express abundant levels
      of pacemaker genes such as endogenous HCN4, Cx45, Cx30.2, Tbx2, and Tbx3. These
      cells were passaged, frozen, and thawed multiple times while maintaining their
      pacemaker-nodal phenotype. When cultured as 3D aggregates in an attempt to create
      a critical mass that simulates in vivo architecture, these cell lines exhibited
      an increase in the expression level of key regulators of cardiovascular
      development, such as GATA4 and GATA6 transcription factors. In addition, the
      aggregate culture system resulted in an increase in the expression level of
      several ion channels that play a major role in the spontaneous diastolic
      depolarization characteristic of pacemaker cells. We have isolated pure
      populations of SAN and AVN cells that will be useful tools for generating
      biological pacemakers.

PMID- 23877225
TI  - The overexpression of P21-activated kinase 5 (PAK5) promotes paclitaxel
      chemoresistance of epithelial ovarian cancer.
AB  - P21-activated kinase 5 (PAK5) is the recently identified member of the group II
      p21-activated kinases (PAKs) family, which is characterized by a highly conserved
      amino-terminal Cdc42/Rac interactive binding domain and a carboxyl terminal
      kinase domain. However, the role of PAK5 in gynecological cancers has not been
      evaluated so far. It is remarkable that we found PAK5 was overexpressed in
      epithelial ovarian cancer (EOC), which is faced with an obstacle of paclitaxel
      resistance. Therefore, in this study, we aim to examine the PAK5 expression
      during EOC progression, the role of PAK5 in malignant progression of EOC and the
      probable relationship between PAK5 and EOC paclitaxel resistance. By
      immunohistochemistry, our results showed that PAK5 expression was increased with
      EOC progression through the adenoma to carcinoma sequence, with the highest
      expression level in invasive and metastatic EOCs. Furthermore, the expression
      level of PAK5 was also found to increase in accordance with the development of
      EOC Federation International of Gynecology and Obstetrics stages (P = 0.038) and
      differentiation grades (P = 0.008). Remarkably, those patients who recurred
      within 6 months after accepting tumor reductive surgery and the following
      carboplatin + paclitaxel chemotherapy had the highest PAK5 expression (P =
      0.015). Moreover, in in vitro studies, we found that SK-OV-3 cell growth was
      decreased while paclitaxel chemosensitivity was correspondingly increased with
      the down-regulation of PAK5. Taken together, our study demonstrated that PAK5 is
      correlated to human EOC and increased PAK5 expression promotes EOC progression,
      and PAK5 regulates EOC cell paclitaxel chemoresistance.

PMID- 23877226
TI  - Feasibility, validity and reliability of the plank isometric hold as a field
      based assessment of torso muscular endurance for children 8-12 years of age.
AB  - This project examined the feasibility, validity, and reliability of the plank
      isometric hold for children 8-12 years of age. 1502 children (52.5% female)
      performed partial curl-up and/or plank protocols to assess plank feasibility (n =
      823, 52.1% girls), validity (n = 641, 54.1% girls) and reliability (n = 111,
      47.8% girls). 12% (n = 52/431) of children could not perform a partial curl-up,
      but virtually all children (n = 1066/1084) could attain a nonzero score for the
      plank. Plank performance without time limit was influenced by small effects with
      age (beta = 6.86; p < .001, eta(2) = 0.03), flexibility (beta = 0.79; p < .001,
      eta(2) = 0.03), and medium effects with cardiovascular endurance (beta = 1.07; p
      < .001, eta(2) = 0.08), and waist circumference (beta = -0.92; p < .001, eta(2) =
      0.06). Interrater (ICC = 0.62; CI = 0.50, 0.75), intra-rater (ICC = 0.83; CI =
      0.73, 0.90) and test-retest (ICC = 0.63; CI = 0.46, 0.75) reliability were
      acceptable for the plank without time limit. These data suggest the plank without
      time limit is a feasible, valid and reliable assessment of torso muscular
      endurance for children 8-12 years of age.

PMID- 23877228
TI  - Cardiovascular adaptation in people with multiple sclerosis following a twelve
      week exercise programme suggest deconditioning rather than autonomic dysfunction
      caused by the disease. Results from a randomized controlled trial.
AB  - BACKGROUND: Guidelines for optimal exercise doses in people with multiple
      sclerosis (MS) have to be established. We need to ascertain the basic
      physiological and perceptual response and adaptation to different exercise doses
      in this clinical population. AIM: The aim of this paper was to explore the
      response during maximal and sub-maximal exercise in people with MS prior to and
      following two different twelve week exercise programmes. DESIGN: Sub-analysis of
      per protocol exercise data of a two group, single blinded, randomised control
      trial. SETTING: Multicentre (community leisure and rehabilitation centres).
      POPULATION: Participants with MS assigned to a continuous (N.=12; mean+/-SE
      age=52.3+/-2.08; Barthel index median & range=19&13-20) or interval (N.=9; mean+/
      SE age=49.3+/-3.5; Barthel index median & range=19&18-20) exercise programme.
      METHODS: Cardiovascular, respiratory and perceptual exercise response and
      adaption was measured at maximal and sub-maximal levels of physical exercise
      prior to and following a twelve week exercise programme, delivered at different
      intensities. RESULTS: Irrespective of the type of exercise programme followed,
      there was a significant increase in peak power (z=-1.98; P=0.05) and normalised
      oxygen uptake during unloaded cycling (z =-2.00; P=0.05). At discharge from the
      exercise programmes, the cardiovascular response to sub-maximal exercise had
      significantly changed (t(360) =-4.62; p<0.01). CONCLUSION: The response in people
      with MS at maximal and sub-maximal levels of physical exercise following a twelve
      week programme is analogous to non-diseased adults. CLINICAL REHABILITATION
      IMPACT: Cardiovascular adaptation in people with MS following a twelve week
      exercise programme suggests deconditioning rather than autonomic dysfunction
      caused by the disease.

PMID- 23877227
TI  - Modulation of corticospinal excitability dependent upon imagined force level.
AB  - Motor imagery is defined as the mental execution of a movement without any muscle
      activity. In the present study, corticospinal excitability was assessed by motor
      evoked potentials (MEPs) when the subjects imagined isometric elbow flexion at
      various force levels. Electromyography was recorded from the right
      brachioradialis, the biceps brachii and the triceps brachii muscles. First, the
      maximum voluntary contraction (MVC) of elbow flexion was recorded in each
      subject. Subjects practiced performing 10, 30 and 60 % MVC using visual feedback.
      After the practice, MEPs were recorded during the imagery of elbow flexion with
      the forces of 10, 30 and 60 % MVC without any feedback. After the MEPs recording,
      we assigned subjects to reproduce the actual elbow flexion force at 10, 30 and 60
      % MVC. The MEPs amplitudes in the brachioradialis and biceps brachii in the 60 %
      MVC condition were significantly greater than those in the 10 % MVC condition (p
      < 0.05). These findings suggest that the enhancement of corticospinal
      excitability during motor imagery is associated with an increase in imagined
      force level.

PMID- 23877230
TI  - In vivo characterization of protein uptake by yeast cell envelope: single cell
      AFM imaging and MU-tip-enhanced Raman scattering study.
AB  - Direct detection of biological transformations of single living cells in vivo has
      been performed by the advanced combination of local topographic imaging by Atomic
      Force Microscopy (AFM) and label-free sub-surface chemical characterization using
      new MU-Tip-Enhanced Raman Spectroscopy (MU-TERS). The enhancing mechanism for MU
      TERS tips with micrometre range radius differs significantly to that of the
      conventional tapered structures terminated by a sharp apex and conditioned by the
      effects of propagating instead of localizing surface plasmon resonance phenomena.
      Sub-wavelength light confinement in the form of a nonradiative evanescent wave
      near the tip surface with penetration depth in the sub-micrometre range opens the
      way for monitoring of subsurface processes near or within the cell wall,
      inaccessible by other methods. The efficiency of the approach has been
      demonstrated by the analysis of the cell envelope of genetically modified (by
      glucose dehydrogenase (GDH) gene bearing Kluyveromyces lactis toxin signal
      sequence) yeast cells enriched by GDH protein. The presence of trans-membrane
      fragments in GDH together with the tendency to form active dimers and tetramers
      causes the accumulation of the proteins within the periplasmic space. These
      results demonstrate that the advanced combination of AFM imaging and subsurface
      chemical characterization by the novel MU-TERS technique provides a new
      analytical tool for the investigation of single living cells in vivo. 

PMID- 23877229
TI  - Training meals on wheels volunteers as health literacy coaches for older adults.
AB  - Homebound older adults constitute a "hardly reached" population with respect to
      health communication. Older adults also typically suffer from health literacy
      challenges, which put them at increased risk of adverse health outcomes.
      Suboptimal interactions with providers are one such challenge. Interventions to
      improve interactive health literacy focus on training consumers/patients in
      question preparation and asking. Meals on Wheels volunteers are uniquely suited
      to coach their clients in such interaction strategies. Seventy-three Meals on
      Wheels volunteers participated in workshops to train as health literacy coaches.
      The 3- to 4-hour workshops included units on communicating with older adults, on
      the nature of health literacy, and on the process of interactive health literacy
      coaching. Participants viewed and discussed videos that modeled the targeted
      communication behaviors for older adult patients interacting with physicians.
      They role-played the coaching process. After 9 months, coaches participated in a
      "booster" session that included videos of ideal coaching practices. Evaluation
      questionnaires revealed that participants had favorable reactions to the
      workshops with respect to utility and interest. They especially appreciated
      learning communication skills and seeing realistic videos. A measure of knowledge
      about the workshop material revealed a significant increment at posttest.
      Fidelity of coaching practices with respect to workshop curriculum was confirmed.
      This training in interactive health literacy for community-based lay volunteers
      constitutes one way to implement the National Action Plan to Improve Health
      Literacy for one "hardly reached" population. An online tool kit containing all
      workshop materials is available. 

PMID- 23877231
TI  - Limitations and high pressure behavior of MOF-5 for CO2 capture.
AB  - Porous network structures (e.g. metal-organic frameworks, MOFs) show considerable
      potential in dethroning monoethanol amine (MEA) from being the dominant scrubber
      for CO2 at the fossil-fuel-burning power generators. In contrast to their
      promise, structural stability and high-pressure behavior of MOFs are not well
      documented. We herein report moisture stability, mechanical properties and high
      pressure compression on a model MOF structure, MOF-5. Our results show that MOF-5
      can endure all tested pressures (0-225 bar) without losing its structural
      integrity, however, its moist air stability points at a 3.5 hour safety window
      (at 21.6  degrees C and 49% humidity) for an efficient CO2 capture. Isosteric
      heats of CO2 adsorption at high pressures show moderate interaction energy
      between CO2 molecules and the MOF-5 sorbent, which combined with the large
      sorption ability of MOF-5 in the studied pressure-temperature ranges show the
      viability of this sorbent for CO2 capturing purposes. The combination of the
      physicochemical methods we used suggests a generalized analytical standard for
      measuring viability in CO2 capture operations. 

PMID- 23877232
TI  - Centromere and cytoplasmic staining pattern recognition: a local approach.
AB  - Autoimmune diseases are very serious and also invalidating illnesses. The
      benchmark procedure for their diagnosis is the indirect immunofluorescence (IIF)
      assay performed on the HEp-2 substrate. Medical doctors first determine the
      fluorescence intensity exhibited by HEp-2 wells and then report the staining
      pattern. Despite its pivotal role, IIF is affected by inter- and intra-laboratory
      variabilities demanding for the development of computer-aided-diagnosis tools
      supporting medical doctor decisions. With reference to staining pattern
      recognition, state-of-the-art approaches recognize five main patterns
      characterized by well-defined cell edges. These approaches are based on cell
      segmentation, a task that recent work suggests to be harder than the
      classification itself. In this paper, we extend the panel of detectable HEp-2
      staining patterns, introducing the recognition of centromere and cytoplasmic
      patterns, which have a high specific match with certain autoimmune diseases, from
      other stainings. Since image segmentation algorithms fail on these samples, we
      developed a classification system integrating local descriptors and the bag of
      visual word approach, which represents image contents without the burden of
      segmentation. We tested our approach on a large dataset of HEp-2 images with high
      variability in both fluorescence intensity and staining patterns correctly
      recognizing the 97.12 % of samples. The system has also been validated in a daily
      routine fashion on 108 consecutive IIF analyses of hospital outpatients and
      inpatients, achieving an accuracy rate of 97.22 %. 

PMID- 23877233
TI  - Facial nerve preservation with preoperative identification and intraoperative
      monitoring in large vestibular schwannoma surgery.
AB  - BACKGROUND: Microsurgery is an option of choice for large vestibular schwannomas
      (VSs). Anatomical and functional preservation of facial nerve (FN) is still a
      challenge in these surgeries. FNs are often displaced and morphologically changed
      by large VSs. Preoperative identification of FN with magnetic resonance (MR)
      diffusion tensor tracking (DTT) and intraoperative identification with facial
      electromyography (EMG) may be desirable for improving functional results of FN.
      METHOD: In this retrospective study, eight consecutive cases with large VS (>=30
      mm in maximal extrameatal diameter) were retrospectively studied. FN DTT was
      performed in each case preoperatively. All the cases underwent microsurgical
      resection of the tumor with intraoperative FN EMG monitoring. Correctness of
      prediction for FN location by DTT was verified by the surgeon's inspection.
      Postoperative FN function of each patient was followed up. RESULTS: Preoperative
      identification of FN was possible in 7 of 8 (87.5 %) cases. FN location predicted
      by preoperative DTT agreed to surgical finding in all the 7 cases. FN EMG was
      helpful to locate and protect the FN. Total resection was achieved in 7 of 8
      (87.5 %). All FNs were anatomically preserved. All cases had excellent facial
      nerve function (House-Brackmann Grade I-II). CONCLUSIONS: FN DTT is a powerful
      technique in preoperatively identification of FN in large VS cases. Continuous
      intraoperative FN EMG monitoring is contributive to locating and protecting FNs.
      Radical resection of large VSs as well as favorable postoperative FN outcome is
      available with application of these techniques.

PMID- 23877234
TI  - Different regulatory pathways are involved in the proliferative inhibition of two
      types of leukemia cell lines induced by paclitaxel.
AB  - Paclitaxel, one of the broadest-spectrum anticancer agents, is currently being
      used in the treatment of patients with solid tumors. In the present study, we
      compared the effect of paclitaxel on two types of leukemia cells. Our results
      showed that paclitaxel could inhibit the proliferation of MEL and K562 cells in a
      dose- and time-dependent manner. The mechanism of proliferative inhibition in
      K562 cells treated by paclitaxel was related to the cell cycle arrest in the G2/M
      phase, as well as the induction of apoptosis. By contrast, MEL cells treated by
      paclitaxel showed significant characteristics of necrosis, which indicated that
      the mode of cell death induced by paclitaxel in these two types of leukemia cells
      differed. Advances in research of the cell cycle, apoptosis and necrosis will
      extend our understanding of the mechanisms of paclitaxel-induced cell death,
      particularly in leukemia cells. Further elucidation of the mechanisms of necrosis
      in MEL cells may expedite the development of improved paclitaxel-based regimens
      for cancer therapy. 

PMID- 23877235
TI  - The HDAC inhibitor, panobinostat, induces apoptosis by suppressing the
      expresssion of specificity protein 1 in oral squamous cell carcinoma.
AB  - Inhibitors of histone deacetylases (HDACs) represent a novel class of therapeutic
      anticancer agents. Panobinostat (LBH589) induces apoptosis through the regulation
      of specificity protein 1 (Sp1) in the oral squamous cell carcinoma (OSCC) cell
      lines, HN22 and HSC4. In this study, we analyzed the underlying signaling
      pathways and the mechanisms involved in this process by 3-(4,5-dimethylthiazol-2
      yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, 4',6
      diamidino-2-phenylindole (DAPI) staining, immunocytochemistry and western blot
      analysis. LBH589 significantly reduced cell growth and the sub-G1 cell population
      and induced apoptosis. Sp1 protein expression was significantly reduced following
      treatment with LBH589 in a concentration-dependent manner. Furthermore, LBH589
      upregulated the expression of p27 and p21 and downregulated the expression of
      cyclin D1, myeloid cell leukemia-1 (Mcl-1) and survivin; this led to the
      activation of apoptotic signaling pathways through the increase of Bax expression
      and the decrease of Bid and Bcl-xL expression. Treatment with LBH589 also induced
      the cleavage of caspase-3 and PARP in the HN22 and HSC4 cells. Taken together,
      our data demonstrate that LBH589 induces the apoptosis of OSCC cells by
      suppressing Sp1 expression, indicating that LBH589 may be a promising
      chemotherapeutic agent for the treatment of OSCC.

PMID- 23877236
TI  - Parents' experiences with pediatric care at retail clinics.
AB  - IMPORTANCE: Little is known about the use of retail clinics (RCs) for pediatric
      care. OBJECTIVE: To describe the rationale and experiences of families with a
      pediatrician who also use RCs for pediatric care. DESIGN AND SETTING: Cross
      sectional study with 19 pediatric practices in a Midwestern practice-based
      research network. PARTICIPANTS: Parents attending the pediatrician's office. MAIN
      OUTCOMES AND MEASURES: Parents' experience with RC care for their children.
      RESULTS: In total, 1484 parents (91.9% response rate) completed the self
      administered paper survey. Parents (23.2%) who used the RC for pediatric care
      were more likely to report RC care for themselves (odds ratio, 7.79; 95% CI, 5.13
      11.84), have more than 1 child (2.16; 1.55-3.02), and be older (1.05; 1.03-1.08).
      Seventy-four percent first considered going to the pediatrician but reported
      choosing the RC because the RC had more convenient hours (36.6%), no office
      appointment was available (25.2%), they did not want to bother the pediatrician
      after hours (15.4%), or they thought the problem was not serious enough (13.0%).
      Forty-seven percent of RC visits occurred between 8 am and 4 pm on weekdays or 8
      am and noon on the weekend. Most commonly, visits were reportedly for acute upper
      respiratory tract illnesses (sore throat, 34.3%; ear infection, 26.2%; and colds
      or flu, 19.2%) and for physicals (13.1%). While 7.3% recalled the RC indicating
      it would inform the pediatrician of the visit, only 41.8% informed the
      pediatrician themselves. CONCLUSIONS AND RELEVANCE: Parents with established
      relationships with a pediatrician most often took their children to RCs for care
      because access was convenient. Almost half the visits occurred when the
      pediatricians' offices were likely open.

PMID- 23877237
TI  - Quantitative determination and pattern recognition analyses of bioactive marker
      compounds from Dipsaci Radix by HPLC.
AB  - In this study, quantitative and pattern recognition analyses were developed using
      HPLC/UV for the quality evaluation of Dipsaci Radix. For quantitative analysis,
      five major bioactive compounds were assessed. The separation conditions employed
      for HPLC/UV were optimized using ODS C18 column (250 * 4.6 mm, 5 MUm) with a
      gradient of acetonitrile and water as the mobile phase at a flow rate of 1.0
      mL/min and a detection wavelength of 212 nm. These methods were fully validated
      with respect to linearity, accuracy, precision, recovery, and robustness. The
      HPLC/UV method was applied successfully to the quantification of five major
      compounds in the extract of Dipsaci Radix. The HPLC analytical method for pattern
      recognition analysis was validated by repeated analysis of 17 Dipsaci Radix and
      four Phlomidis Radix samples. The results indicate that the established HPLC/UV
      method is suitable for quantitative analysis.

PMID- 23877238
TI  - Cytotoxic and anti-tumor activities of lignans from the seeds of Vietnamese
      nutmeg Myristica fragrans.
AB  - Four lignans, meso-dihydroguaiaretic acid (DHGA), macelignan, fragransin A2 and
      nectandrin B, were isolated from the seeds of Myristica fragrans (Vietnamese
      nutmeg) and investigated for their cytotoxic activity against eight cancer cell
      lines. Of these, DHGA exhibited potent cytotoxicity against H358 with IC50 value
      of 10.1 MUM. In addition, DHGA showed antitumor activity in allogeneic tumor
      bearing mice model.

PMID- 23877239
TI  - A model to describe the performance of the UASB reactor.
AB  - A dynamic model to describe the performance of the Upflow Anaerobic Sludge
      Blanket (UASB) reactor was developed. It includes dispersion, advection, and
      reaction terms, as well as the resistances through which the substrate passes
      before its biotransformation. The UASB reactor is viewed as several continuous
      stirred tank reactors connected in series. The good agreement between
      experimental and simulated results shows that the model is able to predict the
      performance of the UASB reactor (i.e. substrate concentration, biomass
      concentration, granule size, and height of the sludge bed). 

PMID- 23877240
TI  - Three-dimensional image registration as a tool for forensic odontology: a
      preliminary investigation.
AB  - Frequently, human dentition is utilized for victim identification. This report
      introduces a new human identification technique based on the principle of 3
      dimensional (3D) image registration of the dentition. With the aid of a dry human
      skull, postmortem (PM) and antemortem (AM) scenarios were assumed. The skull in
      its initial state composed the PM scenario. Virtual 3D PM images were
      reconstructed from medical CT images. The AM scenario was achieved by
      reconstructing the missing hard and soft tissues of the skull by dental waxes.
      Virtual 3D AM images were obtained by laser surface scanning. The virtual PM and
      AM images were registered at 2 levels: arch level and tooth level. At arch level,
      the deviation between the 2 images was 0.147 mm for the maxilla and 0.166 mm for
      the mandible. At tooth level, the deviation average ranged from 0.077 to 0.237
      mm. Qualitatively, even image fit was observed for the arches, intact teeth, and
      teeth with minimal deficiencies. As the tooth defect increased, the alignment
      discrepancy increased. It is concluded that 3D image registration ensured an
      accurate superimposition of the 3D images and can be used as a robust tool for
      forensic identification. 

PMID- 23877241
TI  - Sulfide solid electrolyte with favorable mechanical property for all-solid-state
      lithium battery.
AB  - All-solid-state secondary batteries that employ inorganic solid electrolytes are
      desirable because they are potentially safer than conventional batteries. The
      ionic conductivities of solid electrolytes are currently attracting great
      attention. In addition to the conductivity, the mechanical properties of solid
      electrolytes are important for improving the energy density and cycle
      performance. However, the mechanical properties of sulfide electrolytes have not
      been clarified in detail. Here, we demonstrate the unique mechanical properties
      of sulfide electrolytes. Sulfide electrolytes show room temperature pressure
      sintering. Ionic materials with low bond energies and a highly covalent
      character, which is promising for achieving a high ionic conductivity, tend to be
      suitable for room-temperature processing. The Young's moduli of sulfide
      electrolytes were measured to be about 20 GPa, which is an intermediate value
      between those of typical oxides and organic polymers. 

PMID- 23877242
TI  - Global identification of conserved post-transcriptional regulatory programs in
      trypanosomatids.
AB  - While regulatory programs are extensively studied at the level of transcription,
      elements that are involved in regulation of post-transcriptional processes are
      largely unknown, and methods for systematic identification of these elements are
      in early stages. Here, using a novel computational framework, we have integrated
      sequence information with several functional genomics data sets to characterize
      conserved regulatory programs of trypanosomatids, a group of eukaryotes that
      almost entirely rely on post-transcriptional processes for regulation of mRNA
      abundance. This analysis revealed a complex network of linear and structural RNA
      elements that potentially govern mRNA abundance across different life stages and
      environmental conditions. Furthermore, we show that the conserved regulatory
      network that we have identified is responsive to chemical perturbation of several
      biological functions in trypanosomatids. We have further characterized one of the
      most abundant regulatory RNA elements that we discovered, an AU-rich element
      (ARE) that can be found in 3' untranslated region of many trypanosomatid genes.
      Using bioinformatics approaches as well as in vitro and in vivo experiments, we
      have identified three ELAV-like homologs, including the developmentally critical
      protein TbRBP6, which regulate abundance of a large number of trypanosomatid ARE
      containing transcripts. Together, these studies lay out a roadmap for
      characterization of mechanisms that modulate development and metabolic pathways
      in trypanosomatids. 

PMID- 23877243
TI  - An efficient strategy for TALEN-mediated genome engineering in Drosophila.
AB  - In reverse genetics, a gene's function is elucidated through targeted
      modifications in the coding region or associated DNA cis-regulatory elements. To
      this purpose, recently developed customizable transcription activator-like
      effector nucleases (TALENs) have proven an invaluable tool, allowing introduction
      of double-strand breaks at predetermined sites in the genome. Here we describe a
      practical and efficient method for the targeted genome engineering in Drosophila.
      We demonstrate TALEN-mediated targeted gene integration and efficient
      identification of mutant flies using a traceable marker phenotype. Furthermore,
      we developed an easy TALEN assembly (easyT) method relying on simultaneous
      reactions of DNA Bae I digestion and ligation, enabling construction of complete
      TALENs from a monomer unit library in a single day. Taken together, our strategy
      with easyT and TALEN-plasmid microinjection simplifies mutant generation and
      enables isolation of desired mutant fly lines in the F1 generation. 

PMID- 23877244
TI  - The PRP6-like splicing factor STA1 is involved in RNA-directed DNA methylation by
      facilitating the production of Pol V-dependent scaffold RNAs.
AB  - DNA methylation is a conserved epigenetic marker in plants and animals. In
      Arabidopsis, DNA methylation can be established through an RNA-directed DNA
      methylation (RdDM) pathway. By screening for suppressors of ros1, we identified
      STA1, a PRP6-like splicing factor, as a new RdDM regulator. Whole-genome
      bisulfite sequencing suggested that STA1 and the RdDM pathway share a large
      number of common targets in the Arabidopsis genome. Small RNA deep sequencing
      demonstrated that STA1 is predominantly involved in the accumulation of the
      siRNAs that depend on both Pol IV and Pol V. Moreover, the sta1 mutation
      partially reduces the levels of Pol V-dependent RNA transcripts.
      Immunolocalization assay indicated that STA1 signals are exclusively present in
      the Cajal body and overlap with AGO4 in most nuclei. STA1 signals are also
      partially overlap with NRPE1. Localization of STA1 to AGO4 and NRPE1 signals is
      probably related to the function of STA1 in the RdDM pathway. Based on these
      results, we propose that STA1 acts downstream of siRNA biogenesis and facilitates
      the production of Pol V-dependent RNA transcripts in the RdDM pathway. 

PMID- 23877245
TI  - Target recognition, RNA methylation activity and transcriptional regulation of
      the Dictyostelium discoideum Dnmt2-homologue (DnmA).
AB  - Although the DNA methyltransferase 2 family is highly conserved during evolution
      and recent reports suggested a dual specificity with stronger activity on
      transfer RNA (tRNA) than DNA substrates, the biological function is still
      obscure. We show that the Dictyostelium discoideum Dnmt2-homologue DnmA is an
      active tRNA methyltransferase that modifies C38 in tRNA(Asp(GUC)) in vitro and in
      vivo. By an ultraviolet-crosslinking and immunoprecipitation approach, we
      identified further DnmA targets. This revealed specific tRNA fragments bound by
      the enzyme and identified tRNA(Glu(CUC/UUC)) and tRNA(Gly(GCC)) as new but weaker
      substrates for both human Dnmt2 and DnmA in vitro but apparently not in vivo.
      Dnmt2 enzymes form transient covalent complexes with their substrates. The
      dynamics of complex formation and complex resolution reflect methylation
      efficiency in vitro. Quantitative PCR analyses revealed alterations in dnmA
      expression during development, cell cycle and in response to temperature stress.
      However, dnmA expression only partially correlated with tRNA methylation in vivo.
      Strikingly, dnmA expression in the laboratory strain AX2 was significantly lower
      than in the NC4 parent strain. As expression levels and binding of DnmA to a
      target in vivo are apparently not necessarily accompanied by methylation, we
      propose an additional biological function of DnmA apart from methylation. 

PMID- 23877247
TI  - A shape-persistent alleno-acetylenic macrocycle with a modifiable periphery:
      synthesis, chiroptical properties and H-bond-driven self-assembly into a
      homochiral columnar structure.
AB  - A shape-persistent alleno-acetylenic macrocycle, peripherally decorated with
      eight phenolic rings, has been synthesized in enantiomerically pure form. Its
      electronic circular dichroism spectrum features a strong chiroptical response. In
      the solid state, the macrocycle stacks in pillars to form channels and the stacks
      undergo further self-assembly into a three-dimensional porous architecture
      through lateral intermolecular hydrogen-bonding. 

PMID- 23877246
TI  - Graph-based modeling of tandem repeats improves global multiple sequence
      alignment.
AB  - Tandem repeats (TRs) are often present in proteins with crucial functions,
      responsible for resistance, pathogenicity and associated with infectious or
      neurodegenerative diseases. This motivates numerous studies of TRs and their
      evolution, requiring accurate multiple sequence alignment. TRs may be lost or
      inserted at any position of a TR region by replication slippage or recombination,
      but current methods assume fixed unit boundaries, and yet are of high complexity.
      We present a new global graph-based alignment method that does not restrict TR
      unit indels by unit boundaries. TR indels are modeled separately and penalized
      using the phylogeny-aware alignment algorithm. This ensures enhanced accuracy of
      reconstructed alignments, disentangling TRs and measuring indel events and rates
      in a biologically meaningful way. Our method detects not only duplication events
      but also all changes in TR regions owing to recombination, strand slippage and
      other events inserting or deleting TR units. We evaluate our method by simulation
      incorporating TR evolution, by either sampling TRs from a profile hidden Markov
      model or by mimicking strand slippage with duplications. The new method is
      illustrated on a family of type III effectors, a pathogenicity determinant in
      agriculturally important bacteria Ralstonia solanacearum. We show that TR indel
      rate variation contributes to the diversification of this protein family. 

PMID- 23877249
TI  - CADASIL: intracytoplasmic granular osmiophilic material deposits are
      pseudoinclusions.

PMID- 23877250
TI  - Authors' reply.

PMID- 23877251
TI  - Crystal structure and magnetic properties of a new layered sodium nickel
      hydroxide phosphate, Na2Ni3(OH)2(PO4)2.
AB  - Mixed sodium nickel hydroxide phosphate, Na2Ni3(OH)2(PO4)2, has been synthesized
      hydrothermally from the system NiCO3-Na4P2O7-NaCl-H2O. Its monoclinic crystal
      structure has been determined by single crystal X-ray diffraction: a = 14.259(5),
      b = 5.695(2), c = 4.933(1) A, beta = 104.28(3) degrees , space group C2/m, Z = 2,
      rhoc = 3.816 g cm(-3), R = 0.026. The underlying spin model has been
      characterized in terms of first-principles electronic structure calculations. The
      compound is formed by alternating layers of [NiO6] octahedra and [NaO7]
      polyhedra, combined in the [100] direction with tetrahedral [PO4] oxocomplexes
      and hydrogen bonds. The novel phase is treated as an isostructural variant of the
      two-dimensional potassium manganese hydroxide vanadate, K2Mn3(OH)2(VO4)2, which
      can be formally obtained by morphotropic substitutions of all positions in the
      cationic sublattice. The stripe arrangement of Ni(2+) ions (S = 1) within
      [NiO4(OH)2] layers of Na2Ni3(OH)2(PO4)2 is unique in the sense that its magnetic
      topology places it in between widely discussed honeycomb and kagome lattices. The
      Na2Ni3(OH)2(PO4)2 is a low-dimensional magnet, which reaches the short-range
      correlation regime at Tmax = 38.4 K and orders antiferromagnetically at TN = 33.4
      K. 

PMID- 23877253
TI  - Biological waste treatment.

PMID- 23877252
TI  - Pharmacoepidemiological characterisation of zolpidem and zopiclone usage.
AB  - PURPOSE: Zolpidem and zopiclone are two widely used non-benzodiazepine hypnotics
      whose usage seems to be associated to pharmacodependence. However, to our
      knowledge, there has as yet been no published epidemiological study which has
      compared their abuse or dependence potential. We used a pharmacoepidemiological
      approach to identify and characterise zolpidem and zopiclone users in real life
      situations. METHODS: Regular users of zolpidem or zopiclone were identified in
      the database of a French regional health insurance organisation. A latent class
      analysis (LCA) was used to identify different subgroups of users of these two
      hypnotics. RESULTS: The study cohort comprised 25,168 patients who regularly used
      zolpidem and 21,860 who regularly used zopiclone. The results of the latent class
      analysis, which enables subgroups with similar patterns of response to be
      identified, revealed four clinical subtypes of users of zolpidem: non-problematic
      users, users with associations with hypnotics/anxiolytics or with associated
      mental disorders, and problematic users. Only three subgroups were identified for
      zopiclone, and LCA did not discriminate a special class of problematic users for
      this drug. CONCLUSION: Our analysis indicates that there is a subclass of
      zolpidem user suggestive of abuse; this was not the case for zopiclone. This
      methodology is very interesting because it allows analysis of databases and
      determination of a specific signature of drugs potentially leading to abuse or
      dependence.

PMID- 23877254
TI  - Use of organic waste for the production of added-value holocellulases with
      Cellulomonas flavigena PR-22 and Trichoderma reesei MCG 80.
AB  - We evaluated the production of holocellulases from the cellulolytic
      microorganisms Cellulomonas flavigena PR-22 and Trichoderma reesei MCG 80 using
      as substrates the organic fraction of municipal solid waste (OFMSW) and
      digestates from a hydrogenogenic-methanogenic bioenergy production process. The
      first set of experiments (E1) used the mutant actinobacteria C. flavigena PR-22
      whereas another set (E2) used the mutant filamentous fungi T. reesei MCG 80. In
      E1 with OFMSW as substrate, xylanolytic activities ranged from 1800 to 3900
      international units g(holocellulose)(-1) (IU g(hol)(-1)), whereas the
      cellulolytic activities ranged from 220 to 420 IU g(hol)(-1). The variation of
      agitation speed did not have a significant effect on enzyme activity, whereas the
      increase of substrate concentration had a significant negative effect on both
      xylanolytic and cellulolytic activities on a holocellulose feed basis. Regarding
      E2, the OFMSW was evaluated at 1, 2 and 3 % volatile solids (VS). At 2 % VS the
      best filter paper activities were 1200 filter paper units (FPU) l(-1); however,
      in a holocellulase basis the best result was 67 FPU g(hol)(-1), corresponding to
      1 % VS. Next, OFMSW was compared with OFMSW supplemented with lactose, digested
      solids from hydrogenogenic fermentation (D1) and digested solids from a two-stage
      process (D2). Against expectations, no positive effect was found in OFMSW due to
      lactose. The best enzymatic titres were in the order D1 > OFMSW ~ OFMSW + lactose
      > D2. The use of digestates from hydrogenogenic fermentation for enzyme
      production holds promise for waste management. It promotes energy and added-value
      bioproduct generation-a green alternative to common practice of management and
      disposal of organic wastes.

PMID- 23877255
TI  - Domestic organic waste treatment through vermitechnology.

PMID- 23877256
TI  - Expansion of invasive cardiac services in the United States.
AB  - BACKGROUND: The number of hospitals offering invasive cardiac services
      (diagnostic angiography, percutaneous coronary intervention, and coronary artery
      bypass grafting) has expanded, yet national patterns of service diffusion and
      their effect on geographic access to care are unknown. METHODS AND RESULTS: This
      is a retrospective cohort study of all hospitals in fee-for-service Medicare,
      1996 to 2008. Logistic regression identified the relationship between cardiac
      service adoption and the proportion of neighboring hospitals within 40 miles
      already offering the service. From 1996 to 2008, 397 hospitals began offering
      diagnostic angiography, 387 percutaneous coronary intervention, and 298 coronary
      artery bypass grafting (increasing the proportion with services by 3%, 11%, and
      4%, respectively). This capacity increase led to little new geographic access to
      care; the population increase in geographic access to diagnostic angiography was
      1 percentage point; percutaneous coronary intervention 5 percentage points, and
      coronary artery bypass grafting 4 percentage points. Controlling for hospital and
      market characteristics, a 10 percentage point increase in the proportion of
      nearby hospitals already offering the service increased the odds by 10% that a
      hospital would add diagnostic angiography (odds ratio, 1.102; 95% confidence
      interval, 1.018-1.193), increased the odds by 79% that it would add percutaneous
      coronary intervention (odds ratio, 1.794; 95% confidence interval, 1.288-2.498),
      and had no significant effect on adding coronary artery bypass grafting (odds
      ratio, 0.929; 95% confidence interval, 0.608-1.420). CONCLUSIONS: Hospitals are
      most likely to introduce new invasive cardiac services when neighboring hospitals
      already offer such services. Increases in the number of hospitals offering
      invasive cardiac services have not led to corresponding increases in geographic
      access.

PMID- 23877257
TI  - Rightsizing invasive cardiac services in the United States.

PMID- 23877258
TI  - A tale of two leaks.

PMID- 23877259
TI  - Ca2+/calmodulin-dependent protein kinase II and protein kinase A differentially
      regulate sarcoplasmic reticulum Ca2+ leak in human cardiac pathology.
AB  - BACKGROUND: Sarcoplasmic reticulum (SR) Ca(2+) leak through ryanodine receptor
      type 2 (RyR2) dysfunction is of major pathophysiological relevance in human heart
      failure (HF); however, mechanisms underlying progressive RyR2 dysregulation from
      cardiac hypertrophy to HF are still controversial. METHODS AND RESULTS: We
      investigated healthy control myocardium (n=5) and myocardium from patients with
      compensated hypertrophy (n=25) and HF (n=32). In hypertrophy, Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII) and protein kinase A (PKA) both
      phosphorylated RyR2 at levels that were not different from healthy myocardium.
      Accordingly, inhibitors of these kinases reduced the SR Ca(2+) leak. In HF,
      however, the SR Ca(2+) leak was nearly doubled compared with hypertrophy, which
      led to reduced systolic Ca(2+) transients, a depletion of SR Ca(2+) storage and
      elevated diastolic Ca(2+) levels. This was accompanied by a significantly
      increased CaMKII-dependent phosphorylation of RyR2. In contrast, PKA-dependent
      RyR2 phosphorylation was not increased in HF and was independent of previous beta
      blocker treatment. In HF, CaMKII inhibition but not inhibition of PKA yielded a
      reduction of the SR Ca(2+) leak. Moreover, PKA inhibition further reduced SR
      Ca(2+) load and systolic Ca(2+) transients. CONCLUSIONS: In human hypertrophy,
      both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca(2+) leak. In
      the transition from hypertrophy to HF, the diastolic Ca(2+) leak increases and
      disturbed Ca(2+) cycling occurs. This is associated with an increase in CaMKII-
      but not PKA-dependent RyR2 phosphorylation. CaMKII inhibition may thus reflect a
      promising therapeutic target for the treatment of arrhythmias and contractile
      dysfunction.

PMID- 23877260
TI  - Exercise standards for testing and training: a scientific statement from the
      American Heart Association.

PMID- 23877262
TI  - Li+ ion doping: an approach for improving the crystallinity and upconversion
      emissions of NaYF4:Yb3+, Tm3+ nanoparticles.
AB  - The application of upconversion nanoparticles (UCNPs), especially in vivo, has so
      far been hampered by their relatively low upconversion efficiency. In this work,
      a strategy of Li(+) doping was revisited with the aim of enhancing UV to blue UC
      luminescence of NaYF4:Yb(3+), Tm(3+) nanocrystals. We have demonstrated that the
      short wavelength UC emission bands were indeed significantly enhanced. Compared
      to lithium-free NaYF4:Yb(3+), Tm(3+), the UC emission intensities of 452 nm and
      479 nm of the NPs co-doped with 7 mol% Li(+) ions were increased by 8 and 5
      times, respectively. The mechanism of the enhancement was discussed and the
      improvement of the nanoparticles' crystallinity and the distortion of the local
      symmetry around the Tm(3+) ions, when the Li(+) ions were introduced, were
      confirmed to be the origin of the improvement. 

PMID- 23877261
TI  - Targeting cancer stem cells in glioblastoma multiforme using mTOR inhibitors and
      the differentiating agent all-trans retinoic acid.
AB  - Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, portends
      a poor prognosis despite current treatment modalities. Recurrence of tumor growth
      is attributed to the presence of treatment-resistant cancer stem cells (CSCs).
      The targeting of these CSCs is therefore essential in the treatment of this
      disease. Mechanistic target of rapamycin (mTOR) forms two multiprotein complexes,
      mTORC1 and mTORC2, which regulate proliferation and migration, respectively.
      Aberrant function of mTOR has been shown to be present in GBM CSCs. All-trans
      retinoic acid (ATRA), a derivative of retinol, causes differentiation of CSCs as
      well as normal neural progenitor cells. The purpose of this investigation was to
      delineate the role of mTOR in CSC maintenance, and to establish the mechanism of
      targeting GBM CSCs using differentiating agents along with inhibitors of the mTOR
      pathways. The results demonstrated that ATRA caused differentiation of CSCs, as
      demonstrated by the loss of the stem cell marker Nestin. These observations were
      confirmed by western blotting, which demonstrated a time-dependent decrease in
      Nestin expression following ATRA treatment. This effect occurred despite
      combination with mTOR (rapamycin), PI3K (LY294002) and MEK1/2 (U0126) inhibitors.
      Expression of activated extracellular signal-regulated kinase 1/2 (pERK1/2) was
      enhanced following treatment with ATRA, independent of mTOR pathway inhibitors.
      Proliferation of CSCs, determined by neurosphere diameter, was decreased
      following treatment with ATRA alone and in combination with rapamycin. The
      motility of GBM cells was mitigated by treatment with ATRA, rapamycin and LY29002
      alone. However, combination treatment augmented the inhibitory effect on
      migration suggesting synergism. These findings indicate that ATRA-induced
      differentiation is mediated via the ERK1/2 pathway, and underscores the
      significance of including differentiating agents along with inhibitors of mTOR
      pathways in the treatment of GBM.

PMID- 23877264
TI  - In vivo lymph node mapping and pattern of metastasis spread in locally advanced
      mid/low rectal cancer after neoadjuvant chemoradiotherapy.
AB  - PURPOSE: The lymph node status is one of the strongest prognostic determinants in
      rectal cancers. After chemoradiotherapy (CRT), lymph nodes are difficult to
      detect. This study aims to evaluate the feasibility of lymph node mapping in the
      mesorectum after CRT to analyze the pattern of metastasis spread and to assess
      the reliability of blue dye injection in sentinel lymph node detection. METHOD:
      Ten patients with cN+ mid/low RCs after CRT were prospectively enrolled. The
      protocol scheduled intraoperative blue dye injection, surgery, and specimen
      examination with fat clearance technique. The mesorectum was divided into three
      equal "levels" (upper, middle, and lower); each level was divided into three
      equal "sectors" (right anterolateral, posterior, and left anterolateral). Lymph
      nodes were defined "small" if <=5 mm. RESULTS: Two hundred seventy-six lymph
      nodes were retrieved in ten patients; 76.5 % were small lymph nodes. Six patients
      were pN+ (33 metastatic lymph nodes, 76 % small); small lymph node analysis
      upstaged one patient from N0 to N1 and four patients from N1 to N2. Metastasis
      distribution across sectors was continuous, without "skip sectors." The blue dye
      detected the sentinel lymph node in all patients; in half of the cases, it was
      out of the tumor sector. Blue dye identified 69.7 % of metastatic lymph nodes;
      its sensitivity decreased together with the metastatic deposit size (84 %
      macrometastases, 28.6 % micrometastases, 0 % occult tumor cells; p = 0.004).
      CONCLUSION: The fat clearance technique should be the standard pathological
      examination in patients with RCs after CRT; N staging was improved by small lymph
      node identification. Lymph node metastases have a continuous spread through
      mesorectal sectors. Blue dye injection is effective in sentinel lymph node
      detection.

PMID- 23877265
TI  - Minimally invasive approaches for thoracic decompression from discectomy to
      corpectomy.
AB  - Surgical approaches to the thoracic spine have evolved in recent decades with the
      development of advanced instrumentation techniques and an increased emphasis on
      reducing surgical morbidity. Multiple methods to access this area have been
      described, from a conventional open to a more minimally invasive approach, such
      as anterior-based, via supra- or transmanubrium, via thoracoscopy, lateral-based
      approach, extreme lateral mini-thoracotomy, and dorsolateral approaches,
      transpedicular, costotransversectomy and the lateral extracavitary access. The
      technique used is often determined by the affected spinal level, pathological
      process, and surgeon preference. Each of these approaches requires expertise in
      the specific technique, and has its own complication profile. Over time, these
      techniques have undergone improvement to limit approach-related morbidity and
      minimize soft tissue dissection, resulting in better patient outcomes. These
      different approaches present distinct advantages and disadvantages for which a
      thorough understanding of the regional anatomy is required to avoid approach
      related complications. For these reasons, surgeon experience and confidence in
      the various techniques are major factors in the decision-making process and
      patient outcomes. 

PMID- 23877266
TI  - The role of minimally invasive techniques in the management of spinal neoplastic
      disease: a review.
AB  - This review article provides a general overview of the role of minimal access
      spine surgery (MASS) in the context of spinal neoplastic disease. Illustrative
      cases included outline advances in new techniques with a focus on improved
      patient outcome. The article challenges the traditional indication for surgical
      decompression by considering the objective of better local control of tumor. MASS
      can be used to improve focused environments in which the delivery of a higher and
      safer dose of radiation can be accomplished. This combination of treatment has
      the purpose of better overall survival for some cancer patients by positively
      influencing local control. The role of surgical intervention in the context of
      managing cancer patients is continuously being redefined for this challenging
      population. The modern surgeon must stay abreast of all advances in their field
      in order to provide the best care for their patients. 

PMID- 23877267
TI  - Minimally invasive spine surgery in chronic low back pain patients.
AB  - Low back pain (LBP) is a common disorder with a lifetime prevalence of 85%. The
      pathophysiology of LBP can be various depending on the underlying problem. Only
      in about 10% of the patients specific underlying disease processes can be
      identified. Patients with scoliosis, spondylolisthesis, herniated discs, adjacent
      disc disease, disc degeneration, failed back surgery syndrome or pseudoartrosis
      all have symptoms of LBP in different ways. Chronic low back pain patients are
      advised to stay active, however, there is no strong evidence that exercise
      therapy is significantly different than other nonsurgical therapies. Not every
      patient with symptoms of LBP is an appropriate candidate for surgery. Even with
      thorough systematic reviews, no proof can be found for the benefit of surgery in
      patients with low back pain, without serious neurologic deficit. And subjects
      like psychologic and socio-demographic factors also seem to be influencing a
      patients perception of back pain, expectations of treatment, and outcomes of
      treatment. Open lumbar fusion procedures are typically lengthy procedures and
      require a long exposure, which may result in ischemic necrosis of the paraspinal
      musculature, atrophy, and prolonged back pain. Minimally invasive spine surgery
      needed to take care of a decrease in muscle injuries due to retraction and
      avoidance of disruption of the osseotendineous complex of the paraspinal muscles,
      especially the multifidus attachment to the spinous process and superior
      articular process. Therefore, effort has been made to develop percutaneous
      fusion, as well as fixation methods, which avoid the negative effects of open
      surgery. Several minimally invasive fusion strategies have been described, like
      anterior lumbar interbody fusion (ALIF), posterior lumbar interbody fusion
      (PLIF), transforaminal lumbar interbody fusion (TLIF) and two lateral approaches
      (XLIF and DLIF), all with pro's and con's compared to open surgery and each
      other. The effect of MIS of all type is that patients have less blood loss,
      faster postoperative ambulation, lower use of opioids, and shorter in hospital
      stay, which is nearly always significantly better than an open procedure. And
      most of the studies show a significant improvement of VAS leg-and back pain,
      Oswestry Disability Index and a high fusion rate, but most of the times not
      significantly different than the open counterpart. When it comes to cost
      effectiveness there is a trend in favor of MIS, but to when we want to
      differentiate MIS from open surgery, comorbidities and complications
      significantly affect general and disease-specific outcome measures. In our
      opinion, the actual better outcome of minimal invasive surgery comes down to
      obtain a good cost-effectiveness study, provided that minimally invasive surgery
      has an equal or better clinical and radiologic outcome, given that socio
      economic, demographic and psychological influencers are equal for both types of
      surgery. There are no studies done on the subject MIS and low back pain solely.
      Deriving answers from the difference in VAS back pain in MIS studies reveal a
      100% improvement of back pain after surgery. But that does not imply that this
      procedure, which is still in its childhood, will be the solution to all low back
      pain patients. 

PMID- 23877263
TI  - Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated
      autophagy during metabolic stress.
AB  - The Ser/Thr Rho kinase 1 (ROCK1) is known to have major roles in a wide range of
      cellular activities, including those involved in tumour metastasis and apoptosis.
      Here we identify an indispensable function of ROCK1 in metabolic stress-induced
      autophagy. Applying a proteomics approach, we characterize Beclin1, a proximal
      component of the phosphoinositide 3-kinase class III lipid-kinase complex that
      induces autophagy, as an interacting partner of ROCK1. Upon nutrient deprivation,
      activated ROCK1 promotes autophagy by binding and phosphorylating Beclin1 at
      Thr119. This results in the specific dissociation of the Beclin1-Bcl-2 complex
      without affecting the Beclin1-UVRAG interaction. Conversely, inhibition of ROCK1
      activity increases Beclin1-Bcl-2 association, thus reducing nutritional stress
      mediated autophagy. Genetic knockout of ROCK1 function in mice also leads to
      impaired autophagy as evidenced by reduced autophagosome formation. These results
      show that ROCK1 acts as a prominent upstream regulator of Beclin1-mediated
      autophagy and maintains a homeostatic balance between apoptosis and autophagy. 

PMID- 23877268
TI  - Management of upper cervical spine injuries: a review.
AB  - Upper cervical spine injuries are commonly associated with trauma and require
      significant forces to produce. When these injuries occur they can have
      devastating functional consequences. The distinctive anatomy of the upper
      cervical spine leads injuries to occur in predictable patterns. Injuries can
      occur to the unique osseus structures or ligamentous connections. Common injuries
      include occipital condylar fractures, atlanto-occipital dislocation, fractures of
      the ring of C1, ligamentous injuries involving the ring of C1, and the three
      types of fractures of C2, pars fractures, odontoid fractures and C2 body
      fractures. We present these common injuries found in the occipital-atlantoaxial
      complex and their management based on the current and historical literature. 

PMID- 23877270
TI  - Effect of preconditioning with hyperbaric oxygen on neural cell apoptosis after
      spinal cord injury in rats.
AB  - AIM: The aim of this study was to study the effect of preconditioning with
      hyperbaric oxygen on neural cell apoptosis after spinal cord injury in rats at
      different times, and to study the mechanism of neuroprotection with hyperbaric
      oxygen preconditioning after spinal cord injury. METHODS: Fifty-five adult
      Sprague-Dawley rats were randomly divided into 3 groups, a hyperbaric oxygen
      preconditioning group (Hoping, N.=25), a normal injury group (NI, N.=25) and a
      control group (CON, N.=5). The acute spinal cord injury rat models were
      established using Allen's method, the spinal cord injury selections were obtained
      separately after injury day 1, 5, 7, 10 and 14, the neural cell apoptosis after
      the spinal cord injury in the rat was detected by the HE staining and TUNEL
      method. RESULTS: The TUNEL-positive apoptotic cells were found in both the
      hyperbaric oxygen preconditional group and in the normal injury group. However,
      There was a statistically significant difference between each group (P<0.05). In
      the hyperbaric oxygen preconditioning group, the number of apoptotic cells
      decreased, while the neurofunction of the spinal cord was improved compared with
      the other two groups. CONCLUSION: HBO preconditioning can reduce the number of
      apoptotic cells and promote the nerve functional recovery in rats after spinal
      cord injury, which provide some experimental basis for currently clinical
      hyperbaric oxygen therapy.

PMID- 23877269
TI  - Controversies in the management of cervical spondylotic myelopathy.
AB  - AIM: Cervical spondylotic myelopathy (CSM) is a common clinical entity that can
      be a significant cause of disability in the adult population. Although our CSM
      knowledge has markedly grown in recent years, a variety of controversies exist
      regarding the optimal treatment strategies. The goal of this paper is to review
      and discuss current areas of controversy in the management of CSM patients.
      METHODS: Topics addressed in this manuscript include: operative versus
      nonoperative management for patients with mild CSM, optimal surgical approaches
      for CSM, the utility of intraoperative monitoring, and radiographical prognostic
      indicators for outcome following surgery for CSM. RESULTS: A current review
      reveals several areas where Class I evidence exists regarding these
      controversies. However, many other studies consist contain Class III or weaker
      data, thereby making it difficult to draw any definitive conclusions. Despite the
      lack of a consensus in some areas, it appears that CSM patients can often achieve
      satisfactory treatment through a variety of different options. CONCLUSION: CSM
      remains a challenging clinical problem where several areas of controversy still
      exist. Large, multi-center, randomized prospective trials will be required to
      help resolve some of the controversies.

PMID- 23877271
TI  - Cognitive deficits in patients with low and high grade gliomas.
AB  - AIM: Studies in the literature with specific information concerning the
      neuropsychological alterations in patients with high and low grade gliomas are
      poor. The aim of the present study was to investigate and compare the cognitive
      functioning in patients with high and low-grade glioma pre- and postoperatively.
      METHODS: Between January 2009 and January 2011 27 patients with high-grade glioma
      (HG group) and 15 patients with low-grade glioma (LG group) were
      neuropsychologically assessed in the preoperative time, as well as 6 months and 1
      year after surgery. During the examination, memory, visuo-constructive abilities,
      language and executive functions were tested. In addition in the preoperative
      time, the effect on cognition of lateralization, size and edema was analyzed for
      each group. RESULTS: Both in the HG and LG group statistical comparisons of the
      pre- and postoperative assessments of cognitive abilities showed a postoperative
      improvement in memory functions and in processing speed (P<0.05). In particular
      the analysis of the significance of clinical factors in the postoperative outcome
      of patients with glioma showed that lesion size, edema and lateralization affect
      cognitive functioning in varying degree. CONCLUSION: These findings demonstrated
      different levels of impairments in executive and memory domains and in processing
      speed in patients with low and high grade gliomas. These deficits may have a
      strong impact on quality of life. Psychiatric interventions may be useful for
      patients and their families; in particular for helping the patient to become
      aware of the illness, in bolstering coping strategies, and for facilitating their
      support at home.

PMID- 23877272
TI  - Clinical features and analysis in 1385 Chinese patients with pituitary adenomas.
AB  - AIM: The prevalence of pituitary adenomas (PAs) is increasing as the development
      of imaging techniques. Few studies systematically documented the profile of these
      tumors in Chinese population. Our study is aimed to investigate the clinical
      features of PAs including the clinicopathologies, manifestations, and tumor
      recurrence. METHODS: A retrospective analysis of clinic records of patients
      (median age, 39 years) with PAs was performed. A total of 1385 patients diagnosed
      and treated surgically at Tongji hospital, Hubei Province, China during the years
      1987 through 2009 were identified that met our inclusion criteria and formed the
      study group. RESULTS: The distribution of each PA subtype was nonfunctioning
      pituitary adenomas (NFPA) occupying 40.0% of the total subjects, pure prolactin
      secreting (PRL+) adenomas 18.6%, mixed adenomas 14.4%, growth hormone-secreting
      (GH+) adenomas 6.0%, follicle-stimulating hormone/luteinizing hormone-secreting
      (FSH/LH+) adenomas 5.9%, adrenocorticotropic hormone-secreting (ACTH+) adenomas
      4.6%, and thyroid-stimulating hormone-secreting (TSH+) adenomas 0.6%. The most
      common initial symptoms were visual disturbances (N.=664), endocrine disturbances
      (N.=645), and headaches (N.=532). Patients who complained of endocrine
      disturbances mostly presented menstrual dysfunction in females whereas acromegaly
      in males. A total of 45 cases developed to recurrence, most of which occurred
      within 3 years after surgery. PRL+ adenoma showed the lowest frequency of
      recurrence (0.8%). CONCLUSION: Most adenomas were secretory PAs, with
      prolactinomas being the most common subtype. Visual defects, endocrine disorders,
      and headaches were the most common symptoms. Patients with PRL+ adenoma had the
      lowest chance to undertake recurrence. More clinical care and research activities
      are needed to improve the outcome of these patients.

PMID- 23877273
TI  - Analysis of presurgery time as a prognostic factor in traumatic acute subdural
      hematoma.
AB  - AIM: Head trauma is the most commonly seen trauma mechanism which has the highest
      mortality rate in traffic accident. More than 1000 cases are registered every
      year in our institution. The mechanical forces applied to the head can create
      simple wound, skull fracture, and intracranial bleeding. Many factors affect the
      outcome. Mortality rate of acute traumatic subdural hematoma (ASDH) can reach 40
      90%. Despite the principle of "golden hour" for ASDH patients, there is niehter
      no evidence to support it nor any surgeon management to duplicate. The purpose of
      this study was to analyze the presurgery time, i.e., the time elapsed from the
      accident to the definitive treatment, as a prognostic factor that might influence
      the mortality rate of traumatic acute subdural hematoma. METHODS: Consecutive
      patients who underwent surgical intervention for traumatic ASDH between April
      2009 and April 2011 were enrolled in the study. Their data were collected and
      classified into variables. Statistical measure using multivariate logistic
      regression was applied to search any relationship between presurgery time and
      patients' outcome. RESULTS: The study enrolled 93 patients, mostly male (75.3%).
      There were 6 cases of mild head injury, 28 of moderate and 58 of severe injury.
      Time passed between accident and operation, in overall, was 19.6 hours, with a
      range between 4-54 hours. CONCLUSION: Many factors affect the outcome of ASDH.
      Rapid transport to hospital with neurosurgery facility was associated with better
      outcomes. Being retrospective, this study has its own limitation. Future studies
      should recruit a larger number of patients.

PMID- 23877274
TI  - A theoretically exact reconstruction algorithm for helical cone-beam differential
      phase-contrast computed tomography.
AB  - Differential phase-contrast computed tomography (DPC-CT) reconstruction problems
      are usually solved by using parallel-, fan- or cone-beam algorithms. For rod
      shaped objects, the x-ray beams cannot recover all the slices of the sample at
      the same time. Thus, if a rod-shaped sample is required to be reconstructed by
      the above algorithms, one should alternately perform translation and rotation on
      this sample, which leads to lower efficiency. The helical cone-beam CT may
      significantly improve scanning efficiency for rod-shaped objects over other
      algorithms. In this paper, we propose a theoretically exact filter-backprojection
      algorithm for helical cone-beam DPC-CT, which can be applied to reconstruct the
      refractive index decrement distribution of the samples directly from two
      dimensional differential phase-contrast images. Numerical simulations are
      conducted to verify the proposed algorithm. Our work provides a potential
      solution for inspecting the rod-shaped samples using DPC-CT, which may be
      applicable with the evolution of DPC-CT equipments. 

PMID- 23877275
TI  - ASNC model coverage policy: Cardiac positron emission tomographic imaging.

PMID- 23877276
TI  - Different behavior of water in confined solutions of high and low solute
      concentrations.
AB  - Water-glycerol solutions confined in 21 A pores of the silica matrix MCM-41 C10
      have been studied using differential scanning calorimetry (DSC) and broadband
      dielectric spectroscopy (BDS). The results suggest a micro-phase separation
      caused by the confinement. Likely the water molecules coordinate to the hydroxyl
      surface groups of the pores, leaving most of the glycerol molecules in the centre
      of the pores. This makes the dynamics of glycerol almost concentration
      independent up to water concentrations of about 85 wt%. However, at higher water
      concentrations no substantial clustering of glycerol molecules should occur and
      the glass transition related dynamics exhibit an anomalous behaviour. Instead of
      a common plasticization effect of water, as for the corresponding bulk solutions
      (when no ice is formed), it is evident that water acts as an anti-plasticizer in
      the confinement at high water concentrations. We propose that the increased water
      concentration slows down the glass transition related dynamics in the deeply
      supercooled regime due to that a rigid hydrogen bonded network structure of water
      molecules is formed at low temperatures and low glycerol concentrations. This is
      in contrast to the situation in a homogenously mixed bulk solution of a high
      solute concentration where the water molecules will be less hydrogen bonded, and
      therefore are typically more mobile than the surrounding solute molecules. An
      almost complete hydrogen bonded network of water molecules may, even in
      confinements, be sufficiently rigid to slow down the relaxation of embedded
      solute molecules. It can also be expressed the other way around, i.e. small
      amounts of glycerol act as a plasticizer for water, due to its breaking up of the
      nearly tetrahedral network structure. From the here observed concentration
      dependent behaviour of the deeply supercooled bulk and confined solutions it
      seems, furthermore, evident that the Tg value of bulk water cannot be estimated
      from extrapolations of aqueous solutions. 

PMID- 23877277
TI  - A combinatorial approach to the structure elucidation of a pyoverdine siderophore
      produced by a Pseudomonas putida isolate and the use of pyoverdine as a taxonomic
      marker for typing P. putida subspecies.
AB  - The structure of a pyoverdine produced by Pseudomonas putida, W15Oct28, was
      elucidated by combining mass spectrometric methods and bioinformatics by the
      analysis of non-ribosomal peptide synthetase genes present in the newly sequenced
      genome. The only form of pyoverdine produced by P. putida W15Oct28 is
      characterized to contain alpha-ketoglutaric acid as acyl side chain, a
      dihydropyoverdine chromophore, and a 12 amino acid peptide chain. The peptide
      chain is unique among all pyoverdines produced by Pseudomonas subspecies strains.
      It was characterized as -L-Asp-L-Ala-D-AOHOrn-L-Thr-Gly-c[L-Thr(O-)-L-Hse-D-Hya-L
      Ser-L-Orn-L-Hse-L-Ser-O-]. The chemical formula and the detected and calculated
      molecular weight of this pyoverdine are: C65H93N17O32, detected mass 1624.6404
      Da, calculated mass 1624.6245. Additionally, pyoverdine structures from both
      literature reports and bioinformatics prediction of the genome sequenced P.
      putida strains are summarized allowing us to propose a scheme based on
      pyoverdines structures as tool for the phylogeny of P. putida. This study shows
      the strength of the combination of in silico analysis together with analytical
      data and literature mining in determining the structure of secondary metabolites
      such as peptidic siderophores. 

PMID- 23877278
TI  - Ghrelin attenuates intestinal ischemia/reperfusion injury in mice by activating
      the mTOR signaling pathway.
AB  - Intestinal ischemia/reperfusion (I/R) injury is a serious condition in intensive
      care patients, resulting in severe inflammation and remote organ damage. The
      activation of the mammalian target of rapamycin (mTOR)/p70 ribosomal S6 kinase
      (p70S6K) signaling pathway exerts protective effect against ischemia/reperfusion
      injury. Ghrelin, an orexigenic hormone, inhibits the release of pro-inflammatory
      cytokines, such as interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-6.
      In this study, we investigated the effects of ghrelin on gut I/R injury and the
      regulation of the mTOR/p70S6K signaling pathway following gut I/R injury in mice.
      C57BL/6 mice underwent superior mesenteric artery occlusion for 45 min, followed
      by reperfusion for 4 h. Ghrelin was administered at the onset of reperfusion. We
      assessed survival, organ injury variables, pro-inflammatory cytokine expression
      and observed the histological changes of the small intestine and lungs. Our
      results revealed that the administration of ghrelin inhibited the release of
      certain pro-inflammatory cytokines, reduced neutrophil infiltration, attenuated
      organ injury and improved survival following gut I/R injury. The administration
      of D-Lys-GHRP6, a specific ghrelin receptor antagonist, to a certain extent,
      counteracted the protective effects of ghrelin in gut I/R-induced organ injury
      and mortality. To determine whether the beneficial effects of ghrelin following
      gut I/R injury are associated with the mTOR/p70S6K signaling pathway, the
      phosphorylation levels of mTOR and p70S6K were detected by western blot analysis.
      Our results revealed that mTOR and p70S6K phosphorylation increased in the tissue
      from the small intestine and pulmonary tissue in the animals treated with
      ghrelin. These findings suggest that ghrelin attenuates organ injury following
      gut I/R by promoting the activation of the mTOR/p70S6K signaling pathway.

PMID- 23877279
TI  - Statistical shape model of a liver for autopsy imaging.
AB  - PURPOSE: Modeling the postmortem liver for autopsy imaging is a challenging
      problem owing to the variation in organ deformation found in cadavers and limited
      availability of postmortem liver CT scans. An algorithm was developed to
      construct a statistical shape model (SSM) for the adult postmortem liver in
      autopsy imaging. METHODS: First, we investigated the relationship between SSMs
      obtained from in vivo liver CT scans and those from postmortem cases. Liver
      shapes were embedded in level set functions and statistically modeled using a
      spatially weighted principal components analysis. The performance of the SSMs was
      evaluated in terms of generalization and specificity. Several algorithms for the
      transformation from in vivo livers to postmortem livers were proposed to enhance
      the performance of an SSM for a postmortem liver, followed by a comparative study
      on SSMs. Specifically, five SSMs for a postmortem liver were constructed and
      evaluated using 32 postmortem liver labels, and postmortem liver labels
      synthesized from 144 in vivo liver labels were constructed using the proposed
      transformation algorithms. We also compared the proposed SSMs with three
      conventional SSMs trained from postmortem liver labels and/or in vivo liver
      labels. RESULTS: The investigation showed that the performance of an SSM
      constructed using in vivo liver labels suffered when describing postmortem liver
      shapes. Two of the five proposed SSMs trained using synthesized postmortem livers
      showed the best performance with no significant differences between them, and
      they statistically outperformed all conventional SSMs tested. CONCLUSIONS: The
      performance of conventional SSMs can be improved by using both postmortem liver
      shape labels and artificial shape labels synthesized from in vivo liver shape
      labels.

PMID- 23877280
TI  - Automated aorta segmentation in low-dose chest CT images.
AB  - PURPOSE: Abnormalities of aortic surface and aortic diameter can be related to
      cardiovascular disease and aortic aneurysm. Computer-based aortic segmentation
      and measurement may aid physicians in related disease diagnosis. This paper
      presents a fully automated algorithm for aorta segmentation in low-dose non
      contrast CT images. METHODS: The original non-contrast CT scan images as well as
      their pre-computed anatomy label maps are used to locate the aorta and identify
      its surface. First a seed point is located inside the aortic lumen. Then, a
      cylindrical model is progressively fitted to the 3D image space to track the
      aorta centerline. Finally, the aortic surface is located based on image intensity
      information. This algorithm has been trained and tested on 359 low-dose non
      contrast CT images from VIA-ELCAP and LIDC public image databases. Twenty images
      were used for training to obtain the optimal set of parameters, while the
      remaining images were used for testing. The segmentation result has been
      evaluated both qualitatively and quantitatively. Sixty representative testing
      images were used to establish a partial ground truth by manual marking on several
      axial image slices. RESULTS: Compared to ground truth marking, the segmentation
      result had a mean Dice Similarity Coefficient of 0.933 (maximum 0.963 and minimum
      0.907). The average boundary distance between manual segmentation and automatic
      segmentation was 1.39 mm with a maximum of 1.79 mm and a minimum of 0.83 mm.
      CONCLUSION: Both qualitative and quantitative evaluations have shown that the
      presented algorithm is able to accurately segment the aorta in low-dose non
      contrast CT images.

PMID- 23877281
TI  - Local noise estimation in low-dose chest CT images.
AB  - PURPOSE: Image noise in computed tomography (CT) images may have significant
      local variation due to tissue properties, dose, and location of the X-ray source.
      We developed and tested an automated tissue-based estimator method for estimating
      local noise in CT images. METHOD: An automated TBE method for estimating the
      local noise in CT image in 3 steps was developed: (1) Partition the image into
      homogeneous and transition regions, (2) For each pixel in the homogeneous
      regions, compute the standard deviation in a 15 x 15 x 1 voxel local region using
      only pixels from the same homogeneous region, and (3) Interpolate the noise
      estimate from the homogeneous regions in the transition regions. Noise-aware fat
      segmentation was implemented. Experiments were conducted on the anthropomorphic
      phantom and in vivo low-dose chest CT scans to validate the TBE, characterize the
      magnitude of local noise variation, and determine the sensitivity of noise
      estimates to the size of the region in which noise is computed. The TBE was
      tested on all scans from the Early Lung Cancer Action Program public database.
      The TBE was evaluated quantitatively on the phantom data and qualitatively on the
      in vivo data. RESULTS: The results show that noise can vary locally by over 200
      Hounsfield units on low-dose in vivo chest CT scans and that the TBE can
      characterize these noise variations within 5 %. The new fat segmentation
      algorithm successfully improved segmentation on all 50 scans tested. CONCLUSION:
      The TBE provides a means to estimate noise for image quality monitoring,
      optimization of denoising algorithms, and improvement of segmentation algorithms.
      The TBE was shown to accurately characterize the large local noise variations
      that occur due to changes in material, dose, and X-ray source location.

PMID- 23877282
TI  - The DSM-5 and the art of medicine: certainly uncertain.

PMID- 23877283
TI  - Proteomics applied to the authentication of fish glue: application to a 17th
      century artwork sample.
AB  - This work provides the first identification of fish glue from a few micrograms of
      a 17(th) century artwork sample using an adapted proteomics approach. Fish glue
      has been widely used as a binder in various art objects such as paintings,
      manuscripts or polychrome objects however its authentication remains particularly
      challenging. The lack of information on fish species in genomic and proteomic
      databases represents a major drawback. A supplementary difficulty is provided by
      the historical sample features, i.e. a few micrograms of a 17(th) century
      polychrome object with a multilayered structure. SYPRO(r) Ruby staining was used
      as a screening technique to probe the presence of proteins in the sample cross
      section. Results revealed the presence of several layers containing proteins
      among which a thin proteinaceous layer located between the silver leaf and the
      glaze. This thin layer is described as fish glue coating by historical sources
      but its composition has not been identified yet. The optimized methodology, based
      on high resolution mass spectrometry and adapted bioinformatic tools, was
      successfully applied to 50 MUg of a polychromy sample and resulted in the
      identification of several collagen proteins. Extensive interpretation of data
      generated by tandem mass spectrometry allowed the identification of proteins from
      different biological origins. In particular, seven peptides specific to fish
      collagen proteins were identified for the first time proving the presence of fish
      glue in the sample and corroborating information found in historical texts
      dealing with the polychromy technique. 

PMID- 23877284
TI  - Wave modes of collective vortex gyration in dipolar-coupled-dot-array magnonic
      crystals.
AB  - Lattice vibration modes are collective excitations in periodic arrays of atoms or
      molecules. These modes determine novel transport properties in solid crystals.
      Analogously, in periodical arrangements of magnetic vortex-state disks,
      collective vortex motions have been predicted. Here, we experimentally observe
      wave modes of collective vortex gyration in one-dimensional (1D) periodic arrays
      of magnetic disks using time-resolved scanning transmission x-ray microscopy. The
      observed modes are interpreted based on micromagnetic simulation and numerical
      calculation of coupled Thiele equations. Dispersion of the modes is found to be
      strongly affected by both vortex polarization and chirality ordering, as revealed
      by the explicit analytical form of 1D infinite arrays. A thorough understanding
      thereof is fundamental both for lattice vibrations and vortex dynamics, which we
      demonstrate for 1D magnonic crystals. Such magnetic disk arrays with vortex-state
      ordering, referred to as magnetic metastructure, offer potential implementation
      into information processing devices. 

PMID- 23877286
TI  - What do I do now?: clinical decision making by new graduates.
AB  - Newly graduated nurses (NGNs) are thrust into roles that some purport they are
      inadequately prepared to handle. This study investigated the experience of NGNs
      as they made clinical judgments in the critical care setting. Three themes
      emerged: developing confidence in practice, seeking assistance, and decision
      making. Nursing professional development educators can use the results to
      coordinate an education plan that extends beyond formal orientation and provides
      support for NGNs throughout the first year of practice. 

PMID- 23877285
TI  - Novel insulin receptor substrate 1 and 2 variants in breast and colorectal
      cancer.
AB  - The insulin/insulin-like growth factor pathway is involved in breast and
      colorectal cancer (CRC) development. In the present study, we analyzed the coding
      region and short intron-exon borders of the insulin receptor substrate 1 and 2
      (IRS-1 and IRS-2) genes in 12 cell lines derived from breast cancer (BC), 14 cell
      lines derived from CRC and 33 primary CRCs. The nucleotide variants identified in
      BC were 3 in IRS-1, 1 of which (p.Arg267Cys) was novel and with a pathogenic
      potential as predicted by in silico analysis and 6 in IRS-2. Twenty-one variants
      in IRS-1 and 18 in IRS-2 were identified in the CRC samples. These included 11
      novel IRS-1 variants detected exclusively in CRCs, which included 5 missense
      (p.Pro559Leu, p.Gln655His, p.Asp1014Gly, p.Asp1181His and pPro1203Ser) with a
      pathogenic potential as predicted by in silico analysis, 2 frameshifts predicted
      to generate a truncated protein, 1 splice-site mutation and 3 silent variants. In
      the CRC samples we also identified 7 novel IRS-2 variants, including 4 missense
      variants, which included 2 (p.Asp782Asn and p.Gly1230Ser) with a pathogenic
      potential as predicted by in silico analysis, 2 frame insertion mutations and 1
      silent variant. Most of the novel IRS-1 and IRS-2 variants may be involved in the
      modulation of IRS-1 or IRS-2 functions and could be relevant to breast and
      colorectal tumorigenesis.

PMID- 23877287
TI  - Promoting nurses' knowledge in evidence-based practice: do educational methods
      matter?
AB  - Evidence-based practice (EBP) is a mandate for nursing practice. Education on EBP
      has occurred in academic settings, but not all nurses have received this
      training. The authors describe a randomized controlled pretest/posttest design
      testing the differences in effectiveness of two educational methods to improve
      nurses' knowledge, attitudes, and practice of EBP. Results indicated both methods
      improved self-reported practice. On the basis of the study findings, staff
      development educators can select the teaching method that best complements their
      organizational environment. 

PMID- 23877288
TI  - Nursing portfolio study: the use in annual performance reviews.
AB  - Professional portfolios allow staff to document their participation in areas of
      education, certification, shared governance councils, national nursing
      organizations, and community outreach. In this study, nurses tracked their
      professional development in a virtual electronic portfolio. A
      preperception/postperception questionnaire for both staff and unit directors
      revealed that nursing portfolios proved to be a valuable tool during annual
      performance reviews to acknowledge accomplishments and encourage continued
      professional growth of individual direct-care staff nurses. 

PMID- 23877289
TI  - Evaluation of the effectiveness of simulation for preceptor preparation.
AB  - This quality improvement project focused on addressing perceived gaps in
      preceptor preparation. In addition to realigning course goals with organizational
      priorities, the authors explored the effectiveness of incorporating simulation
      based education into an initial preceptor workshop through measures of
      participant satisfaction, knowledge gain, and follow-up surveys of preceptor
      behaviors. The results obtained from this project support the use of simulation
      based education in preceptor preparation. 

PMID- 23877290
TI  - The helpfulness and timing of transition program education.
AB  - The purpose of this study was to examine relationships between transition program
      education and new graduate nurse transition. Although new graduates preferred
      hands-on learning, the helpfulness of workshops was associated with better
      transition. New graduates, many of whom were from the Millennial Generation,
      liked a variety of educational modalities. Access to support was better for nurse
      graduates who received education delivered throughout the first year of
      transition. 

PMID- 23877291
TI  - Simulation to the rescue! Caring for a pediatric patient in the rural setting.
AB  - Rural nurses are expected to be competent and confident caregivers for patients
      of all ages and disease states. Rural nurse educators are challenged with
      creating appropriate learning environments to assess and maintain nursing
      competencies in resource-limited areas. This project describes and evaluates the
      utilization of a simulation manikin from a local community college to provide a
      hands-on learning environment for rural nurses working with pediatric patients in
      respiratory distress. 

PMID- 23877292
TI  - Successful implementation of evidence-based nursing practice: the indispensable
      role of staff development.
AB  - The professional development department members are instrumental in leading
      nursing research and quality improvement projects. Rarely do academic nurse
      researchers know the staff, culture, and capabilities of an organization like the
      members of the staff development department. Developing a collaborative program
      using the talents of the professional development department members and the
      nurse researcher is a win-win situation and, in this article, describes how it
      successfully assisted the healthcare organization to be awarded the Magnet
      Recognition. 

PMID- 23877293
TI  - Five generations in the nursing workforce: implications for nursing professional
      development.
AB  - Positive patient outcomes require effective teamwork, communication, and
      technological literacy. These skills vary among the unprecedented five
      generations in the nursing workforce, spanning the "Silent Generation" nurses
      deferring retirement to the newest "iGeneration." Nursing professional
      development educators must understand generational differences; address
      communication, information technology, and team-building competencies across
      generations; and promote integration of learner-centered strategies into
      professional development activities. 

PMID- 23877294
TI  - Simulation programs versus simulation centers in the hospital/workplace setting:
      it's not about the space.

PMID- 23877295
TI  - Striving to meet the needs of ANPD membership.

PMID- 23877297
TI  - Letter to the editor.

PMID- 23877298
TI  - The author responds.

PMID- 23877300
TI  - Epitaxial growth and lithium ion conductivity of lithium-oxide garnet for an all
      solid-state battery electrolyte.
AB  - Epitaxial thin films of Al-doped Li7La3Zr2O12 (LLZO) with a cubic garnet-type
      structure were successfully synthesized using pulsed laser deposition to
      investigate the lithium ion conduction in grains. Two orientations of the films
      were obtained depending on the Gd3Ga5O12 (GGG) substrate orientation,
      LLZO(001)/GGG(001) and LLZO(111)/GGG(111). The ionic conductivities in the grains
      of the (001) and (111) films were 2.5 * 10(-6) and 1.0 * 10(-5) S cm(-1) at 298
      K, respectively, which were lower than those of polycrystalline LLZO of over 10(
      4) S cm(-1). X-ray reflectometry and inductively coupled plasma mass spectrometry
      revealed a large amount of Al(3+) of over 0.6 moles substituted for Li(+). These
      results indicate that the Al(3+) substitution in the LLZO lattice decreases the
      number of movable lithium ions and blocks the three-dimensional lithium migration
      pathway. The lattice mismatch between the film and the substrate induced the
      lattice distortion of the LLZO, resulting in different conductivities between the
      (001) and (111) films. The epitaxial-film model system directly clarified a
      substantial impact of the Al substitution and the lattice distortion on the
      lithium ion conductivity in the LLZO. 

PMID- 23877302
TI  - DNA unmethylome profiling by covalent capture of CpG sites.
AB  - Dynamic patterns of cytosine-5 methylation and successive hydroxylation are part
      of epigenetic regulation in eukaryotes, including humans, which contributes to
      normal phenotypic variation and disease risk. Here we present an approach for the
      mapping of unmodified regions of the genome, which we call the unmethylome. Our
      technique is based on DNA methyltransferase-directed transfer of activated groups
      and covalent biotin tagging of unmodified CpG sites followed by affinity
      enrichment and interrogation on tiling microarrays or next generation sequencing.
      Control experiments and pilot studies of human genomic DNA from cultured cells
      and tissues demonstrate that, along with providing a unique cross-section through
      the chemical landscape of the epigenome, the methyltransferase-directed transfer
      of activated groups-based approach offers high precision and robustness as
      compared with existing affinity-based techniques. 

PMID- 23877301
TI  - The revised EuroSCORE II for the prediction of mortality in patients undergoing
      transcatheter aortic valve implantation.
AB  - BACKGROUND: The assessment of procedural risk is crucial in patients with severe
      symptomatic aortic stenosis. Logistic EuroSCORE and STS score are currently used
      to estimate procedural risk and mortality for surgical and transcatheter aortic
      valve implantation (TAVI). The recently published EuroSCORE II might provide a
      helpful tool. METHODS: The new EuroSCORE II was calculated in 206 patients
      undergoing transfemoral TAVI and compared to the established logistic EuroSCORE
      and STS mortality score. Discriminative power and calibration of each test was
      statistically evaluated. RESULTS: 30-day and 1-year mortality rates were 6.8 %
      (14/206) and 27.2 % (56/206). In-hospital mortality rate was 29.2 +/- 17.8 % with
      logistic EuroSCORE, 9.5 +/- 6.8 % with STS score, and 9.22 +/- 7.12 % with
      EuroSCORE II: Logistic EuroSCORE and EuroSCORE II were significantly increased in
      non-survivors compared to survivors at 30 days and at 1 year. EuroSCORE II and
      STS score (r = 0.49, p < 0.001) showed moderate correlation, whereas strong
      correlation was found between EuroSCORE II and logistic EuroSCORE (r = 0.71, p <
      0.001). ROC curve analyses for the prediction of 30-day mortality (AUC 0.79 vs.
      0.69 vs. 0.71) and 1-year mortality (AUC 0.72 vs. 0.70 vs. 0.70) were performed.
      Statistical comparison revealed no difference between the AUCs (p > 0.05).
      CONCLUSION: In percutaneous TAVI patients, 30-day mortality was best approximated
      by the new EuroSCORE II, whereas the logistic EuroSCORE best reflected 1-year
      mortality. However, EuroSCORE II does not provide additional prognostic
      information beyond the established logistic EuroSCORE. For more exact risk
      prediction in TAVI, a distinct TAVI risk score would be desirable.

PMID- 23877303
TI  - Biochemical and thermodynamic characteristics of thermo-alkali-stable xylanase
      from a novel polyextremophilic Bacillus halodurans TSEV1.
AB  - The purified extracellular xylanase of polyextremophilic Bacillus halodurans
      TSEV1 has been visualized as a single band on SDS-PAGE and eluted as single peak
      by gel filtration, with a molecular mass of 40 kDa. The peptide finger print and
      cloned xylanase gene sequence analyses indicate that this enzyme belongs to GH
      family 10. The active site carboxyl residues are mainly involved in catalysis,
      while tryptophan residues are involved in substrate binding. The enzyme is
      optimally active at 80  degrees C and pH 9.0, and stable in the pH range of 7.0
      12.0 with T 1/2 of 35 min at 80  degrees C (pH 9.0). Activation energy for birch
      wood xylan hydrolysis is 30.51 kJ mol(-1). The K m, V max and k cat (birchwood
      xylan) are 2.05 mg ml(-1), 333.33 MUmol mg(-1 )min(-1) and 3.33 * 10(4) min(-1),
      respectively. The pKa1 and pKa2 of ionizable groups of the active site that
      influence V max are 8.51 and 11.0. The analysis of thermodynamic parameters for
      xylan hydrolysis suggests this as a spontaneous process. The enzyme is resistant
      to chemical denaturants like urea and guanidinium-HCl. The site-directed
      mutagenesis of catalytic glutamic acid residues (E196 and E301) resulted in a
      complete loss of activity. The birch wood xylan hydrolyzate contained xylobiose
      and xylotriose as the main products without any trace of xylose, and the enzyme
      hydrolyzes xylotetraose and xylopentaose rapidly to xylobiose. Thermo-alkali
      stability, resistance to various chemical denaturants and mode of action make it
      a useful biocatalyst for generating xylo-oligosaccharides from agro-residues and
      bleaching of pulp in paper industries.

PMID- 23877304
TI  - Co3O4-carbon nanotube heterostructures with bead-on-string architecture for
      enhanced lithium storage performance.
AB  - In this report, alkylcarboxyl group-decorated carbon nanotubes (CNTs) with
      clustered functionalization patterns are achieved based on a modified Birch
      reduction in liquid ammonia. By using these functional CNTs (f-CNTs), a new type
      of Co3O4-CNT heterostructure is prepared via a simple hydrothermal method. SEM
      and TEM analyses reveal that the as-synthesized Co3O4-CNT heterostructures
      exhibit bead-on-string architecture, in which the Co3O4 spheres are threaded with
      CNTs. A possible growth mechanism is proposed to explain the formation of these
      Co3O4-CNT heterostructures. The electrochemical properties of the Co3O4-CNT
      heterostructures as anode materials for lithium ion batteries are investigated.
      The Co3O4-CNT heterostructures display high electrochemical activity, good cycle
      stability and improved rate performance. Such a large improvement of the
      electrochemical performance can be related to the robust necklace-like
      architectures which possess properties such as high mechanical stability,
      excellent electric conductivity and good strain accommodation. 

PMID- 23877306
TI  - Comparison of sublingual midazolam and dexmedetomidine for premedication in
      children.
AB  - BACKGROUND: Premedication in children scheduled for surgery reduces preoperative
      anxiety and facilitates a smooth induction of anesthesia. Midazolam is a commonly
      used premedication in children but, because of its undesirable effects such as
      postoperative behavior changes and cognitive impairment, it is not an ideal
      premedicant. Dexmedetomidine, a highly specific a2-adrenergic receptor agonist,
      produces sedation which mimics natural stage 2 non-rapid eye movement sleep and
      helps in early postoperative recovery. The objective of our study was to evaluate
      the effectiveness of sublingual dexmedetomidine in comparison to sublingual
      midazolam as premedicant in children METHODS: This prospective, randomized,
      double-blind study enrolled 100 children aged 1 to 12 years belonging to ASA
      physical status I or II scheduled to undergo inguinal hernia repair, orchidopexy
      or circumcision, under general anesthesia. The children were randomly allocated
      into two groups of 50 each. Children in group I were premedicated with sublingual
      midazolam 0.25 mg/kg, while those in group II with sublingual dexmedetomidine 1.5
      ug/kg. Sedation was assessed using a 6-point sedation score. Behavior at
      induction, wake-up behavior and mask acceptance was evaluated using a 4-point
      scoring system. RESULTS: The median sedation score at parental separation was 6
      in group I as compared to 3.5 in group II (P<0.001). The behavior score at
      induction was comparable in both the groups. The median mask acceptance score
      (P<0.001) and wake-up behavior score (P=0.001) in preschool children was 2 in
      group I as compared to 1 in group II. However, in school-aged children both the
      scores were comparable. CONCLUSION: Sublingual dexmedetomidine provides more
      effective preoperative sedation as compared to sublingual midazolam across all
      the age groups and allows a smooth anesthesia induction and awakening especially
      in the preschool children.

PMID- 23877305
TI  - Supplemental single shot femoral nerve block for total hip arthroplasty: impact
      on early postoperative care, pain management and lung function.
AB  - BACKGROUND AND AIM: Peripheral regional anesthesia is beneficial in the
      management of postoperative pain in hip surgery, and can also reduce post
      operative care unit (PACU) stay. Its opioid-sparing actions may also be
      beneficial for respiratory mechanics and pulmonary function. The aim of our pilot
      study was to evaluate the effect of a supplemental single shot femoral block for
      elective total hip arthroplasty on early respiratory function and postoperative
      management within the first 24 postoperative hours. METHODS: We prospectively
      studied 80 patients undergoing total hip arthroplasty. Written informed consent
      was obtained after ethics committee approval. Forty patients were randomLy
      assigned to receive single shot femoral nerve block (FNB) using 15mL bupivacaine
      0.25% and 20 mg clonidine while the remainder received standard treatment without
      nerve block (STN). Premedication and general anesthesia were standardized. Pulse
      oximetry saturation and spirometric lung function were measured preoperatively
      (baseline) and at 0.5 h, 2 h, 6 h and 24 h, after extubation breathing room air.
      PACU surveillance and postoperative pain therapy was standardized. RESULTS:
      Oxygen saturation and spirometry results were significantly better within the FNB
      group during the first six postoperative hours. Although VAS scores during the
      PACU stay did not significantly differ between the study groups, PACU discharge
      criteria were met earlier in the FNB group (116+/-40 min [mean+/-SD] vs. 152+/-47
      min in the STN group). The FNB group exhibited significantly lower VAS scores at
      6 and 24 hours. CONCLUSION: Supplemental single shot femoral nerve block for
      total hip arthroplasty resulted in earlier PACU discharge capability, improved
      lung function during the first six hours and better pain control within the first
      24 postoperative hours.

PMID- 23877307
TI  - Duration of mechanical ventilation after craniosynostosis repair reduces over
      time.
AB  - BACKGROUND: Pediatric craniosynostosis repair (CR) involves wide scalp
      dissections with multiple osteotomies and has been associated with significant
      morbidity. The aim of this study was to document the impact of perioperative
      complications on prolonged mechanical ventilation after CR. METHODS: Data were
      collected from the anesthesia records, Pediatric Intensive Care Unit (PICU)
      progress notes and discharge summaries. All the patients were transferred from
      the operating room sedated and on mechanical ventilation to the PICU. To
      highlight the determinants of prolonged mechanical ventilation we performed a
      logistic regression analysis.. RESULTS: Fifty-five patients underwent CR, but 6
      were excluded due to incomplete records. The main intraoperative complications
      were: metabolic acidosis (32%), hypotension (20%), dural tears laceration (22%)
      and altered coagulation (18%). Metabolic acidosis (46%) and relative polycythemia
      (24%) were detected on arrival to the PICU. All children received intraoperative
      blood products and 23 (46%) were transfused in the postoperative period too. No
      infective complications were detected. The only determinant associated
      significantly with a prolonged mechanical ventilation was to have surgery in the
      first 5 years of the program (P=0.05) (95% CI 0.358-0.996). CONCLUSION: All life
      threatening complications were intraoperative whereas only milder ones, such as
      hypercloremic and lactic acidosis were noticed in PICU. All children are alive
      without any neurological deficit. Even though we deal on a daily basis with
      complex surgical cases, only time, hence experience, showed an impact on
      prolonged mechanical ventilation.

PMID- 23877309
TI  - Impact of PEEP during laparoscopic surgery on early postoperative ventilation
      distribution visualized by electrical impedance tomography.
AB  - BACKGROUND: General anesthesia, mechanical ventilation and pneumoperitoneum
      affect ventilation distribution at different extent. It should be clarified if an
      intraoperative positive end-expiratory pressure (PEEP) level of 10 cmH2O
      influences early postoperative ventilation. Electrical impedance tomography (EIT)
      was used to assess changes in regional ventilation. METHODS: Thirty-two patients
      (ASA physical status I/II) scheduled to undergo elective laparoscopic
      cholecystectomy were enrolled. The patients were randomly assigned to PEEP (10
      cmH2O) or ZEEP group (0 cmH2O). EIT was performed before induction of anesthesia
      (T0) and after admission to the recovery room (T1-4). Ventral/dorsal and
      right/left lung impedance ratio (IR) and the center-of-ventilation index (COV)
      were calculated to investigate the differences in homogeneity of ventilation.
      RESULTS: Compared to preoperative data a significant increase in PaCO2 and
      reduction of pH values could be found in both groups. Significant decrease of
      postoperative tidal impedance change (?Z) as well as a general postoperative
      ventral shift of the ventilation indicated by changes of IR and COV could be
      found in both groups. In ZEEP group IR and COV differed significantly from
      baseline (T0). In PEEP group there was just significant difference in COV at T2
      T4 compared to T0. In the early postoperative period (T1) there was no difference
      in ventilation distribution in PEEP patients. CONCLUSION: Changes of
      postoperative ventilation can be imaged by EIT. Intraoperative PEEP ventilation
      has a positive effect on early postoperative ventilation distribution, even
      though not all PEEP patients benefit from mechanical PEEP ventilation the same
      way. Intraoperative PEEP results in a more homogeneous ventilation distribution
      by trend.

PMID- 23877310
TI  - Update on anesthetic complications of robotic thoracic surgery.
AB  - In the last decade, there has been increasing use of the da Vinci(r) robot
      surgical system to perform minimally invasive thoracic surgery. The robotic
      technology can be applied for surgery of the lungs, mediastinum, and esophagus. A
      number of case reports have been shown steep learning curve, and promising
      surgical outcome with this new technology. However, anesthesia management of the
      robotic thoracic surgery can be complex and requires further education. For
      example, most of the cases require sufficient lung collapse in order to provide
      adequate surgical field. In addition, a unique operative setting, such as patient
      positioning and capnothorax can make anesthesia management further challenging.
      Hence, anesthesiologists should have better awareness of adverse events or
      complications related to the robotic surgery to accomplish successful anesthesia
      management. This review will focus on the potential complications of robotic
      thoracic surgery involving the lungs, mediastinum and esophagus. 

PMID- 23877311
TI  - Weaning from mechanical ventilation and central venous saturation (ScvO2) in
      tracheostomized patients. A fleeting factor for making decisions?

PMID- 23877312
TI  - Gut overgrowth is bad news for the critically ill.

PMID- 23877314
TI  - The effects of NaNbO3 particle size on the photocatalytic activity for 2-propanol
      photodegradation.
AB  - The effects of NaNbO3 particle size on the photocatalytic activity were
      investigated by taking gaseous 2-propanol photodegradation as a model reaction.
      By varying the loading amount of precursors onto mesoporous SBA-15,
      nanocrystalline NaNbO3 samples with particle sizes ranging from 3 to 50 nm were
      successfully synthesized. The particle size and surface area value of templated
      NaNbO3 change systematically with the change in loading amount of the precursors.
      The physicochemical characteristics of the samples were examined by techniques
      such as XRD, SEM, TEM, Raman spectroscopy, and UV-visible diffuse reflectance
      spectroscopy. The optimum NaNbO3 particle size for the highest photocatalytic
      activity was found to be 30 nm. The current study also revealed that the NaNbO3
      photocatalyst is structure sensitive for 2-propanol photodegradation. The density
      of active sites on the sample surface decreases as the particle size decreases.
      Competing effects of factors such as the surface area, changes in electronic
      structure, defect density, and concentration of reaction active sites determine
      the optimum particle size of NaNbO3. 

PMID- 23877313
TI  - What is called symptom?
AB  - There is one concept in medicine which is prominent, the symptom. The
      omnipresence of the symptom seems, however, not to be reflected by an equally
      prominent curiosity aimed at investigating this concept as a phenomenon. In
      classic, traditional or conventional medical diagnostics and treatment, the lack
      of distinction with respect to the symptom represents a minor problem. Faced with
      enigmatic conditions and their accompanying labels such as chronic fatigue
      syndrome, fibromyalgia, medically unexplained symptoms, and functional somatic
      syndromes, the contestation of the symptom and its origin is immediate and
      obvious and calls for further exploration. Based on a description of the
      diagnostic framework encompassing medically unexplained conditions and a brief
      introduction to how such symptoms are managed both within and outside of the
      medical clinic, we argue on one hand how unexplained conditions invite us to
      reconsider and re-think the concept we call a "symptom" and on the other hand how
      the concept "symptom" is no longer an adequate and necessary fulcrum and must be
      enriched by socio-cultural, phenomenological and existential dimensions.
      Consequently, our main aim is to expand both our interpretative horizon and the
      linguistic repertoire in the face of those appearances we label medically
      unexplained symptoms. 

PMID- 23877315
TI  - Declining mortality in neurocritical care patients: a cohort study in Southern
      Alberta over eleven years.
AB  - PURPOSE: Few interventions have been proven to improve outcomes in neurocritical
      care patients. It is unknown whether outcomes in Canada have changed over time.
      We performed a cohort study in Southern Alberta to determine whether survival and
      discharge disposition have improved. METHODS: Using prospectively collected data,
      we identified patients admitted to regional intensive care units (ICUs) over a
      more than 11-year period with traumatic brain injury (TBI), subarachnoid
      hemorrhage (SAH), intracerebral hemorrhage, anoxic encephalopathy, central
      nervous system infection, or status epilepticus. Four sequential time periods of
      2.8 years were compared, as were periods before and after various practice
      modifications were introduced. Logistic regression was used to adjust for patient
      age, Glasgow Coma Scale score, and case mix. RESULTS: A total of 4,097 patients
      were assessed. The odds of death were lowest in the most recent time quartile
      (odds ratio [OR] 0.70, 95% confidence interval [CI] 0.56 to 0.88, P < 0.01). The
      odds of being discharged home without the need for support services increased
      over time (OR 1.45, 95% CI 1.38 to 1.85, P = 0.003). Improvements were not the
      same for all diagnostic subgroups. They were statistically significant for
      patients with TBI and SAH. Neurocritical care consultative services, evidence
      based protocols, and clustering of patients within a multidisciplinary ICU were
      associated with improved outcomes. Length of stay in an ICU increased among
      hospital survivors (4.6 vs 3.8 days, P < 0.01). CONCLUSIONS: Mortality and
      discharge disposition of neurocritical care patients in Southern Alberta have
      improved over time. Practice modifications in the region were associated with
      positive outcome trends. Longer ICU length of stay may imply that intensivists
      are increasingly delaying decisions about withdrawing life-sustaining
      interventions.

PMID- 23877316
TI  - Erlotinib resistance in EGFR-amplified glioblastoma cells is associated with
      upregulation of EGFRvIII and PI3Kp110delta.
AB  - BACKGROUND: The treatment efficacy of epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors like erlotinib has not met expectations for
      glioblastoma therapy, even for EGFR-overexpressing tumors. We determined possible
      mechanisms of therapy resistance using the unique BS153 glioblastoma cell line,
      which has retained amplification of the egfr gene and expression of EGFR variant
      (v)III. METHODS: Functional effects of erlotinib, gefitinib, and cetuximab on
      BS153 proliferation, migration, and EGFR-dependent signal transduction were
      systematically compared in vitro. The tumor-initiating capacity of parental and
      treatment-resistant BS153 was studied in Naval Medical Research
      Institute/Foxn1(nu) mice. Potential mediators of resistance were knocked down
      using small interfering (si)RNA. RESULTS: Erlotinib and gefitinib inhibited
      proliferation and migration of BS153 in a dose-dependent manner, whereas
      cetuximab had no effect. BS153 developed resistance to erlotinib (BS153(resE))
      but not to gefitinib. Resistance was associated with strong upregulation of
      EGFRvIII and subsequent activation of the phosphatidylinositol-3-OH kinase (PI3K)
      pathway in BS153(resE) and an increased expression of the regulatory 110-kDa
      delta subunit of PI3K (p110delta). Knockdown of EGFRvIII in BS153(resE) largely
      restored sensitivity to erlotinib. Targeting PI3K pharmacologically caused a
      significant decrease in cell viability, and specifically targeting p110delta by
      siRNA partially restored erlotinib sensitivity in BS153(resE). In vivo, BS153
      formed highly invasive tumors with an unusual growth pattern, displaying numerous
      satellites distant from the initial injection site. Erlotinib resistance led to
      delayed onset of tumor growth as well as prolonged overall survival of mice
      without changing tumor morphology. CONCLUSIONS: EGFRvIII can mediate resistance
      to erlotinib in EGFR-amplified glioblastoma via an increase in PI3Kp110delta.
      Interfering with PI3Kp110delta can restore sensitivity toward the tyrosine kinase
      inhibitor.

PMID- 23877317
TI  - TGM2 inhibition attenuates ID1 expression in CD44-high glioma-initiating cells.
AB  - BACKGROUND: CD44 is a molecular marker associated with cancer stem cell
      populations and treatment resistance in glioma. More effective therapies will
      result from approaches aimed at targeting glioma cells high in CD44. METHODS:
      Glioma-initiating cell lines were derived from fresh surgical glioblastoma
      samples. Expression of tissue transglutaminase 2 (TGM2) was attenuated through
      lentivirus-mediated short hairpin RNA knockdown. MTT assay [(3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was used to evaluate the
      growth inhibition induced by TGM2 inhibitor. Terminal deoxynucleotidyl
      transferase deoxyuridine triphosphate nick end labeling was used to evaluate cell
      apoptosis following TGM2 inhibition. CD44(+) glioma stem cells were sorted by
      flow cytometry. A nude mice orthotopic xenograft model was used to evaluate the
      in vivo effect of TGM2 inhibitor. RESULTS: TGM2 was highly expressed in CD44-high
      glioblastoma tissues and tumor-derived glioma-initiating cell lines. TGM2
      knockdown impaired cell proliferation and induced apoptosis in CD44-high glioma
      initiating cell lines. Further studies indicated that expression of inhibitor of
      DNA binding 1 protein (ID1) is regulated by TGM2 and might be an important
      mediator for TGM2-regulated cell proliferation in CD44-high glioma-initiating
      cell lines. TGM2 inhibitor reduces ID1 expression, suppresses cell proliferation,
      and induces apoptosis in CD44-high glioma-initiating cell lines. Furthermore,
      TGM2 is highly expressed in CD44(+) glioma stem cells, while pharmacological
      inhibition of TGM2 activity preferentially eliminates CD44(+) glioma stem cells.
      Consistently, TGM2 inhibitor treatment reduced ID1 expression and induced
      apoptosis in our orthotopic mice xenograft model, which can be translated into
      prolonged median survival in tumor-bearing mice. CONCLUSIONS: TGM2 regulates ID1
      expression in glioma-initiating cell lines high in CD44. Targeting TGM2 could be
      an effective strategy to treat gliomas with high CD44 expression.

PMID- 23877319
TI  - Liraglutide ameliorates glycometabolism and insulin resistance through the
      upregulation of GLUT4 in diabetic KKAy mice.
AB  - Liraglutide, a long-lasting glucagon-like peptide-1 analogue, has been used for
      the treatment of patients with type 2 diabetes mellitus since 2009. In this
      study, we investigated the anti-diabetic effects and mechanisms of action of
      liraglutide in a spontaneous diabetic animal model, using KK/Upj-Ay/J (KKAy)
      mice. The KKAy mice were divided into 2 groups, the liraglutide group (mice were
      treated with 250 ug/kg/day liraglutide) and the model group (treated with an
      equivalent amount of normal saline). C57BL/6J mice were used as the controls
      (treated with an equivalent amount of normal saline). The treatment period lasted
      6 weeks. During this treatment period, fasting blood glucose (FBG) levels and the
      body weight of the mice were measured on a weekly basis. Our results revealed
      that liraglutide significantly decreased FBG levels, the area under the curve
      following a oral glucose tolerance test and insulin tolerance test, increased
      serum insulin levels, reduced homeostasis model assessment of insulin resistance
      and increased the insulin sensitivity index. Furthermore, liraglutide ameliorated
      glycometabolism dysfunction by increasing glycolysis via hexokinase and
      glycogenesis via pyruvate kinase activation. An ultrastructural examination of
      the pancreas revealed that liraglutide improved the damaged state of islet beta
      cells and increased the number of insulin secretory granules. The real-time PCR
      results revealed that the gene expression of glucose transporter 4 (GLUT4)
      increased following treatment with liraglutide. Liraglutide also upregulated the
      protein expression of GLUT4 in liver tissue and skeletal muscle. Our results
      suggest that liraglutide ameliorates glycometabolism and insulin resistance in
      diabetic KKAy mice by stimulating insulin secretion, increasing glycogenesis and
      glycolysis and upregulating the expression of GLUT4.

PMID- 23877320
TI  - Medical staff extremity dosimetry in CT fluoroscopy: an anthropomorphic hand
      voxel phantom study.
AB  - This work aims to contribute to the study of the radiation dose distribution
      delivered to the hands of medical staff members during a general computed
      tomographic (CT) fluoroscopic guided procedure. In this study, both Monte Carlo
      simulations and measurements were performed. For free-in-air and computed
      tomography dose index (CTDI) body phantom measurements, a standard pencil
      ionization chamber (IC) 100 mm long was used. The CT scanner model was
      implemented using MCNPX (Monte Carlo N-Particle eXtended) and was successfully
      validated by comparing the simulated results with measurements. Subsequently, CT
      images of a hand, together with an anthropomorphic phantom, were voxelized and
      used with the MCNPX code for dose calculations. The hand dose distribution study
      was performed both by using thermo-luminescent detector measurements and Monte
      Carlo simulations. The validated simulation tool provides a new perspective for
      detailed investigations of CT-irradiation scenarios. Simulations show that there
      is a strong dose gradient, namely the even zones of the hand that are in precise
      vicinity to the x-ray beam only receive about 4% of the maximum dose delivered to
      adjacent areas which are directly exposed to the primary x-ray beam. Finally, the
      scatter contribution of the patient was also studied through MC simulations. The
      results show that for directly exposed parts of the hand surface, the dose is
      reduced by the body of the patient (due to the shielding), whereas the dose is
      increased by scattered radiation from the patient for parts of the skin that
      receive scattered radiation only.

PMID- 23877318
TI  - IDH1/2 mutations target a key hallmark of cancer by deregulating cellular
      metabolism in glioma.
AB  - Isocitrate dehydrogenase (IDH) enzymes have recently become a focal point for
      research aimed at understanding the biology of glioma. IDH1 and IDH2 are mutated
      in 50%-80% of astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary
      glioblastomas but are seldom mutated in primary glioblastomas. Gliomas with
      IDH1/2 mutations always harbor other molecular aberrations, such as TP53 mutation
      or 1p/19q loss. IDH1 and IDH2 mutations may serve as prognostic factors because
      patients with an IDH-mutated glioma survive significantly longer than those with
      an IDH-wild-type tumor. However, the molecular pathogenic role of IDH1/2
      mutations in the development of gliomas is unclear. The production of 2
      hydroxyglutarate and enhanced NADP+ levels in tumor cells with mutant IDH1/2
      suggest mechanisms through which these mutations contribute to tumorigenesis.
      Elucidating the pathogenesis of IDH mutations will improve understanding of the
      molecular mechanisms of gliomagenesis and may lead to development of a new
      molecular classification system and novel therapies. 

PMID- 23877321
TI  - Aptamer-linked biosensor for thrombin based on AuNPs/thionine-graphene
      nanocomposite.
AB  - A novel protocol of electrochemical thrombin aptasensor based on a
      goldnanoparticles/thionine-graphene (AuNPs/Th-G) nanocomposite modified glassy
      carbon electrode was presented. Graphene was non-covalently functionalized by
      thionine viapi-stacking interaction, and then AuNPs were electrodeposited onto
      the Th-G surface. The morphology and conductivity of the AuNPs/Th-G nanocomposite
      were characterized by scanning electron microscopy, cyclic voltammetry and
      electrochemical impedance spectroscopy. The ethanethiol-substituted
      oligonucleotide probe was immobilized onto the surface of the AuNPs/Th-G
      nanocomposite to prepare an electrochemical biosensing platform. The aptamer
      thrombin reaction was monitored by differential pulse voltammetry. Under optimum
      conditions, the proposed biosensor exhibits high sensitivity and a low detection
      limit for thrombin determination. The thrombin could be quantified in a wide
      range of 0.5 to 40 nM and with a low detection limit of 0.093 nM (S/N = 3). 

PMID- 23877323
TI  - Orthopaedic Traumatology: more than a "surgicalist": modified with permission
      from American Academy of Orthopaedic Surgeons. AAOS Now 2013, volume 7, number 6.

PMID- 23877322
TI  - Inhibition of the transcription factor Sp1 suppresses colon cancer stem cell
      growth and induces apoptosis in vitro and in nude mouse xenografts.
AB  - The transcription factor specificity protein 1 (Sp1) plays a role in the
      development and progression of various types of human cancers, while cancer stem
      cells (CSCs) are important in cancer cell self-renewal, resistance to
      chemotherapy and metastatic potential. This study investigated the role of Sp1 in
      colon CSC growth and apoptosis. Colon CSCs were successfully enriched using
      special culture medium and identified by typical CSC gene expression. In a
      quiescent state, these CSCs formed spheres with slow proliferation; overexpressed
      Sp1, CD44, CD166 and CD133 proteins; upregulated mesenchymal markers; and a
      downregulated epithelial marker were noted. In ex vivo experiments, the Sp1
      protein was expressed in 74.8% of colon cancer tissues, whereas it was expressed
      only in 42.2% of the distant normal colon mucosae. Furthermore, inhibition of SP1
      expression using Sp1 siRNA or mithramycin A (MIT) led to marked suppression of
      CSC growth and induced apoptosis. In addition, the percentage of CD44+/CD166+
      cells was significantly downregulated both in vivo and in vitro following Sp1
      inhibition. In conclusion, Sp1 suppression attenuated the characteristics of
      colon CSCs. Thus, Sp1 inhibition may be potentially useful for the future
      development of a novel therapeutic strategy to control colon cancer.

PMID- 23877324
TI  - Mean-field theory of random close packings of axisymmetric particles.
AB  - Finding the optimal random packing of non-spherical particles is an open problem
      with great significance in a broad range of scientific and engineering fields. So
      far, this search has been performed only empirically on a case-by-case basis, in
      particular, for shapes like dimers, spherocylinders and ellipsoids of revolution.
      Here we present a mean-field formalism to estimate the packing density of
      axisymmetric non-spherical particles. We derive an analytic continuation from the
      sphere that provides a phase diagram predicting that, for the same coordination
      number, the density of monodisperse random packings follows the sequence of
      increasing packing fractions: spheres <oblate ellipsoids <prolate ellipsoids
      <dimers <spherocylinders. We find the maximal packing densities of 73.1% for
      spherocylinders and 70.7% for dimers, in good agreement with the largest
      densities found in simulations. Moreover, we find a packing density of 73.6% for
      lens-shaped particles, representing the densest random packing of the
      axisymmetric objects studied so far. 

PMID- 23877325
TI  - Tracking of accelerometer-measured physical activity in early childhood.
AB  - Establishing and maintaining healthy physical activity (PA) levels is important
      throughout life. The purpose of this study was to determine the extent of PA
      tracking between ages 3 and 7 y. Objective measures of PA (RT3, triaxial
      accelerometer) were collected every 4 mo from ages 3-7; data from 234 children
      with PA measures available during each year of age were analyzed. Mean PA (total,
      moderate/vigorous (MV), and inactivity [IA]) was calculated for each year of age
      and adjusted for wear time. Correlations with age 3 PA were moderate at age 4 (r
      = .42-.45) but declined by age 7 (r = .19-.25). After classification into sex
      specific tertiles of PA at age 3, boys in the high age 3 MVPA tertile maintained
      significantly higher PA at all subsequent ages, while girls in the high age 3
      MVPA tertile were not significantly higher at age 6 and 7. Boys and girls in the
      high age 3 IA tertile had significantly higher IA at multiple subsequent years of
      age (p < .05 at ages 5 and 6). In conclusion, boys who were relatively more
      active at age 3 remained more active for several subsequent years. These findings
      highlight early-childhood differences in physical activity patterns between boys
      and girls. 

PMID- 23877326
TI  - Diagnostic value of abdominal free air detection on a plain chest radiograph in
      the early postoperative period: a prospective study in 648 consecutive patients
      who have undergone abdominal surgery.
AB  - BACKGROUND: To the best of our knowledge, this is the first study to evaluate the
      predictive value of free air (on a plain radiograph) for bowel perforation in a
      large prospective cohort of surgical patients. METHODS: All consecutive patients
      undergoing abdominal surgery between January 2011 and June 2012 were screened for
      this study. We performed an upright chest radiograph on the second and third
      postoperative day. Thereafter, additional radiographic evaluations were performed
      every 2 days until the disappearance of abdominal free air. RESULTS: Of the 648
      subjects enrolled in our study, free abdominal air was found in 65 subjects on
      the first radiographic evaluation (2 days after surgery), 51 on the second (3
      days after surgery), three on the third (5 days after surgery), and none on the
      fourth (7 days after surgery). The presence of free abdominal air was associated
      with an increased risk of gastrointestinal perforation. The presence of free air
      was associated with a hazard ratio (HR) of 21.54 (95% CI 9.66-48.01, p<0.001) and
      a HR of 23.87 (95% CI 10.68-53.34, p<0.001) at 2 and 3 days after surgery,
      respectively. Sensitivity, specificity, positive predictive value, and negative
      predictive value were 70, 93, 33, and 98%, respectively, at 2 days after surgery,
      and similar results were confirmed at 3 days after surgery. CONCLUSION: We
      believe that the presence of free air at 3 days after surgery should not be
      considered a common finding. Here, we demonstrate that the detection of free air
      has a remarkable predictive value for gastrointestinal perforation, which has
      been overestimated in previous experience.

PMID- 23877327
TI  - Primary hepatic Ewing's sarcoma with cytogenetic confirmation.
AB  - INTRODUCTION: Extraskeletal Ewing's sarcoma is reported in the medical
      literature, but none has been described as presenting with a resectable liver
      mass. METHODS: A case of a 29-year-old male patient who presented with a large
      symptomatic mass in the right lobe of the liver which, following resection,
      demonstrated the characteristic histopathology and fusion protein (EWSR1-Fli1)
      found in Ewing's sarcoma was reported. DISCUSSION: Complete surgical resection
      offers the best long-term outlook. Cure rates with appropriate surgical and
      chemotherapeutic management range between 30 and 60 %.

PMID- 23877329
TI  - Mesoporous hybrid material composed of Mn3O4 nanoparticles on nitrogen-doped
      graphene for highly efficient oxygen reduction reaction.
AB  - The hybrid material composed of Mn3O4 nanoparticles on nitrogen-doped graphene
      was prepared via a solvothermal process and investigated for the first time as a
      catalyst for oxygen reduction reaction (ORR). Its high ORR activity, excellent
      durability and tolerance to methanol make this hybrid material a promising
      candidate for highly efficient ORR in fuel cells and metal-air batteries. 

PMID- 23877330
TI  - An unusual wide complex ECG.

PMID- 23877328
TI  - Dendritic cell-based immunotherapy targeting synthesized peptides for advanced
      biliary tract cancer.
AB  - BACKGROUND: The aim of this retrospective study was to clarify the safety and
      efficacy of dendritic cell (DC)-based immunotherapy targeting synthesized
      peptides, Wilms tumor 1 (WT1) and Mucin 1, cell surface associated (MUC1) for
      biliary tract cancers (BTCs). METHODS: Sixty-five patients who had nonresectable,
      recurrent, or metastatic BTCs and received the DC-based immunotherapy were
      selected for the study. DCs were pulsed with WT1 and/or MUC1. The adverse events
      (AEs) and clinical responses were examined. RESULTS: No serious treatment-related
      AEs were observed. Median survival time (MST) from diagnosis and from the first
      vaccination was 18.5 and 7.2 months, respectively. By multivariate Cox
      proportional hazard analysis, the significant independent factors were found to
      be (1) combined chemotherapy, (2) albumin level >=4.0 g/dL before vaccination,
      (3) C-reactive protein level <0.5 mg/dL before vaccination, and (4) fever after
      vaccination. The MST from the first vaccination with or without chemotherapy was
      8.2 and 5.3 months, respectively (P = 0.016), and MST for the patients with
      prognostic nutritional index >=40 and <40 was 8.1 and 5.0 months, respectively (P
      = 0.023). CONCLUSIONS: Although a small uncontrolled nonrandomized study, DC
      based immunotherapy for BTCs was safe and produced a clinical response for the
      patients who underwent chemotherapy and maintained a good nutrition status.

PMID- 23877331
TI  - In-situ formation of cobalt-phosphate oxygen-evolving complex-anchored reduced
      graphene oxide nanosheets for oxygen reduction reaction.
AB  - Oxygen conversion process between O2 and H2O by means of electrochemistry or
      photochemistry has lately received a great deal of attention. Cobalt-phosphate
      (Co-Pi) catalyst is a new type of cost-effective artificial oxygen-evolving
      complex (OEC) with amorphous features during photosynthesis. However, can such Co
      Pi OEC also act as oxygen reduction reaction (ORR) catalyst in electrochemical
      processes? The question remains unanswered. Here for the first time we
      demonstrate that Co-Pi OEC does be rather active for the ORR. Particularly, Co-Pi
      OEC anchoring on reduced graphite oxide (rGO) nanosheet is shown to possess
      dramatically improved electrocatalytic activities. Differing from the generally
      accepted role of rGO as an "electron reservoir", we suggest that rGO serves as
      "peroxide cleaner" in enhancing the electrocatalytic behaviors. The present study
      may bridge the gap between photochemistry and electrochemistry towards oxygen
      conversion.

PMID- 23877332
TI  - 14N solid-state NMR: a sensitive probe of the local order in zeolites.
AB  - Local order in as-synthesised zeolites templated by tetraalkylammonium cations is
      proven from solid-state (14)N NMR and related quadrupolar parameters, opening new
      perspectives in the study of porous materials. 

PMID- 23877333
TI  - Traffic of leukocytes and cytokine up-regulation in the central nervous system in
      a murine model of neuroparacoccidioidomycosis.
AB  - BACKGROUND: Paracoccidioidomycosis is the most important systemic mycosis in
      South America. In the last decades, it was observed that central nervous system
      involvement is frequent, occurring in 12.5 % of the cases. The aim of this study
      was to report the early inflammatory changes associated with an experimental
      model of neuroparacoccidioidomycosis (NPCM). METHODS: C57BL/6 mice were infected
      by intracranial route with 10(6) yeast cells of PB18 strain of Paracoccidioides
      brasiliensis. Leukocyte-endothelium interactions were assessed by intravital
      microscopy 1, 2, 4, and 8 weeks post-infection (p.i.). Chemokine/cytokine levels
      in the brain and histopathological changes were assessed 4 and 8 weeks p.i..
      RESULTS: Intravital microscopy analysis revealed a progressive increase in
      leukocyte recruitment in the vessels of pia mater with a peak 4 weeks p.i. The
      chemokine CXCL9 was increased at 4 and 8 weeks p.i., while CCL2, CCL3, and CCL5
      were increased at 8 weeks p.i. Histopathological analysis revealed the
      infiltration of inflammatory cells and the development of progressive
      granulomatous meningoencephalitis. CCL3 levels correlated with clinical
      manifestations of disease, as measured by the SHIRPA battery. CONCLUSIONS: The
      experimental model of NPCM showed increased leukocyte recruitment associated with
      increased expression of chemokines and nervous tissue inflammation which
      correlated with clinical manifestations of disease.

PMID- 23877334
TI  - More equal societies have less mental illness: what should therapists do on
      Monday morning?
AB  - BACKGROUND: Therapists seeing poor clients may ask if countries with greater
      income equality have less mental illness. If so, how should therapists respond?
      MATERIAL: A review of epidemiological studies, theories of inequality and
      democratic reform movements in psychiatry and psychology leads to four arguments.
      DISCUSSION: (1) Increasing income equality improves the health of societies. (2)
      An elite opposes greater equality, partly by persuading the majority to consent
      to the existing order. (3) Therapists may inadvertently help in this persuasive
      effort. (4) However, therapists in democratic traditions create systems of care
      that support movements for greater income equality.

PMID- 23877335
TI  - Being bullied in childhood, and pain and pain perception in adulthood.
AB  - BACKGROUND AND AIMS: While a number of negative health outcomes have been
      associated with bullying in childhood, we are not aware of any studies examining
      relationships between bullying in childhood, and pain symptoms and pain
      perception in adulthood - the focus of the present study. METHODS: Using a cross
      sectional consecutive sample and a self-report survey methodology, we examined
      among 243 primary-care outpatients a history of being bullied in childhood
      (yes/no) in relationship to three pain ratings (now, past month, past year) and
      catastrophic thoughts and feelings about pain as assessed by the Pain
      Catastrophizing Scale (PCS). RESULTS: Being bullied in childhood was
      statistically significantly associated with present pain ratings (p < .001) as
      well as pain ratings over the past month and the past year (p < .01), and with
      the total score on the PCS as well as each of its sub-scales (i.e. rumination,
      magnification, helplessness) (p < .001). CONCLUSIONS: Being bullied in childhood
      is associated with higher reported levels of pain at various time points as well
      as greater levels of self-reported catastrophic thoughts and feelings about pain.
      Importantly, the methodology of this study does not allow for the examination of
      a causal relationship.

PMID- 23877336
TI  - Challenges in assessing depressive symptoms in Fiji: A psychometric evaluation of
      the CES-D.
AB  - BACKGROUND AND AIM: The CES-D is a commonly used self-report assessment for
      depressive symptomatology. However, its psychometric properties have not been
      evaluated in Fiji. This study aims to evaluate the reliability and validity of
      English language and Fijian vernacular versions in ethnic Fijian adolescent
      schoolgirls. METHODS: As part of the HEALTHY Fiji study, ethnic Fijian female
      adolescents (N = 523) completed the CES-D. Participants selected to respond in
      English or the local vernacular. Reliability (internal consistency, item-total
      score correlation, and test-retest estimates), validity (associations with other
      proxies for depression) and factor structure were assessed. Evaluations
      considered differences between language versions. RESULTS: In this sample, the
      CES-D had a Cronbach's alpha of 0.81 and item-total score correlation
      coefficients ranged between 0.2 and 0.63. One week test-retest reliability
      (ICC(2)) was 0.57. CES-D scores were higher among individuals who endorsed
      feelings of depression and suicidality compared to those who did not. ROC
      analyses of the CES-D versus binary depression and suicidality variables produced
      AUCs around 0.70 and did not support a discrete cut-off for significant
      disturbance. Findings were similar across the two language groups. CONCLUSIONS:
      The CES-D has acceptable reliability and validity among ethnic Fijian female
      adolescents in English and in the Fijian vernacular language. Findings support
      its utility as a dimensional measure for depressive symptomatology in this study
      population. Further examination of its clinical utility for case finding for
      depression in Fijian school-based and community populations is warranted.

PMID- 23877337
TI  - Health service utilization by patients with common mental disorder identified by
      the Self-Reporting Questionnaire in a primary care setting in Zomba, Malawi: a
      descriptive study.
AB  - BACKGROUND: There has been no study carried out to assess health service
      utilization by people with common mental disorder (CMD) in Malawi. AIM: The aim
      of the study was to evaluate health service utilization patterns of patients with
      CMD in primary health care (PHC) clinics. METHODS: The study was conducted in two
      PHC clinics in one of the 28 districts in Malawi. Face-to-face interviews with
      the Self-Reporting Questionnaire (SRQ-20) were conducted in a sample of 323 PHC
      attendees aged 18 years and older who attended the PHC clinics for any reason.
      RESULTS: The prevalence of probable CMD in the sample was 20.1%. People with
      probable CMD had a higher mean number of health facility visits in the previous
      three months compared to those without probable CMD (1.6 vs 1.19, p = .02).
      CONCLUSION: The study reveals high utilization of health services for people with
      CMD in the PHC setting. There is a need for PHC workers to improve skills in
      diagnosing patients with CMD to make PHC services more effective by reducing re
      attendance and improving patient outcomes.

PMID- 23877338
TI  - Systematic review of radioguided versus wire-guided localization in the treatment
      of non-palpable breast cancers.
AB  - One-third of breast cancers present as non-palpable lesions. The current gold
      standard treatment for these cancers is localized wide local excision using wire
      guided localization (WGL). WGL has drawbacks including technical and scheduling
      issues resulting in the development of alternative radioguided techniques (RGL).
      A systematic review was performed to identify studies comparing RGL and WGL. The
      outcomes of surgical margin status, re-operation rates, surgical operative time,
      volume and excised specimen weight and successful sentinel lymph node biopsy
      (SLNB) rates were evaluated. Pooled odds ratios (ORs) and 95 % confidence
      intervals were estimated using fixed-effects analyses and random-effects analyses
      in case of statistically significant heterogeneity (p < 0.05). Seven randomized
      controlled trials (RCTs) matching the inclusion criteria were identified. The
      pooled ORs for involved surgical margin status were 0.78 (95 % CI, 0.52-1.17);
      for re-operations 0.74 (95 % CI, 0.49-1.11) and for successful SLNB 1.29 (95 %
      CI, 0.66-2.53). There was a significant difference in surgical operating time in
      favour of RGL (mean difference (MD), -2.95; 95 % CI, -4.43, -1.47) and a
      significant difference in excised specimen volume, favouring WGL (MD, 6.79; 95 %
      CI, 0.03, 13.56). The MD for a specimen weight of -3.00 (95 % CI, -15.15, 9.15)
      showed no significant difference between RGL and WGL. RGL has a reduced operating
      time, but larger volume excisions compared to WGL. There is insufficient evidence
      to support the uptake of RGL over WGL, and larger, adequately powered, multi
      centre RCTs are required. 

PMID- 23877339
TI  - Eribulin mesylate versus ixabepilone in patients with metastatic breast cancer: a
      randomized Phase II study comparing the incidence of peripheral neuropathy.
AB  - Peripheral neuropathy is a common toxicity associated with tubulin-targeted
      chemotherapeutic agents. This Phase II study compares the incidence and severity
      of neuropathy associated with eribulin mesylate or ixabepilone in metastatic
      breast cancer (MBC). The primary objective was to assess the incidence of
      neuropathy; the study was designed to detect a difference in neuropathy rate of
      35 % for eribulin versus 63 % for ixabepilone (odds ratio 0.316, 80 % power, 0.05
      two-sided significance level). Eligibility criteria included: MBC; prior taxane
      therapy; at least one chemotherapy for advanced disease; no or minimal pre
      existing neuropathy (Grade 0 or 1). The intent-to-treat population comprised 104
      patients randomized (1:1) to eribulin mesylate (1.4 mg/m(2), 2-5 min intravenous
      on days 1 and 8) or ixabepilone (40 mg/m(2), 3 h intravenous on day 1) on a 21
      day cycle. 101 patients in the safety population received a median of 5.0
      eribulin and 3.5 ixabepilone cycles. Incidence of neuropathy (any grade) was 33.3
      and 48.0 %, and peripheral neuropathy was 31.4 and 44.0 % for eribulin and
      ixabepilone, respectively. After controlling for pre-existing neuropathy and
      number of prior chemotherapies, these differences were not significant. Compared
      with ixabepilone, fewer patients receiving eribulin discontinued treatment due to
      neuropathy (3.9 vs. 18.0 %) or adverse events (AEs) in general (11.8 vs. 32.0 %).
      Time to onset of neuropathy was 35.9 weeks for eribulin and 11.6 weeks for
      ixabepilone, and time to resolution was 48 versus 10 weeks, respectively; other
      AEs were comparable. Objective responses were 15.4 versus 5.8 % and clinical
      benefit rates were 26.9 versus 19.2 %. In conclusion, after controlling for pre
      existing neuropathy and number of prior chemotherapies, the differences in the
      incidence of neuropathy with eribulin and ixabepilone were not statistically
      significant. Onset of neuropathy tended to occur later with eribulin and resolve
      later. 

PMID- 23877340
TI  - Intra-operative ultrasound versus wire-guided localization in the surgical
      management of non-palpable breast cancers: systematic review and meta-analysis.
AB  - INTRODUCTION: The current standard of treatment for non-palpable breast cancers
      is wire-guided localization (WGL). WGL has its drawbacks and alternatives such as
      radio-guided surgery (RGL) and intra-operative ultrasound (IOUS) have been
      developed. The clinical effectiveness of all forms of RGL has been assessed
      against WGL in previous systematic reviews and meta-analyses. We performed the
      first systematic review and meta-analysis of IOUS in the management of non
      palpable breast cancers. METHODS: Studies were considered eligible for inclusion
      in this systematic review if they (1) assessed the role of surgeon-performed IOUS
      for the treatment of non-palpable breast cancers and ductal carcinoma in situ
      (DCIS) and (2) specified surgical margin excision status. Those studies, which
      were randomized controlled trials (RCTs) or cohort studies with comparison WGL
      groups were included in the meta-analysis. For those studies included in the meta
      analysis, pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were
      estimated using fixed-effects analyses and random-effects analyses in case of
      statistically significant heterogeneity (p < 0.05). RESULTS: Eighteen studies
      reported data on IOUS in 1,328 patients with non-palpable breast cancer and DCIS.
      Nine cohort studies with control WGL groups and one RCT were included in the meta
      analysis. Successful localization rates varied between 95 and 100 % in all
      studies and there was a statistically significant difference in the rates of
      involved surgical margins in favour of IOUS with pooled OR 0.52 (95 % CI 0.38
      0.71). CONCLUSION: Compared with WGL, IOUS reduces involved surgical margin
      rates. Adequately powered RCTs are required to validate these findings.

PMID- 23877341
TI  - Objective assessment of cosmetic outcome after targeted intraoperative
      radiotherapy in breast cancer: results from a randomised controlled trial.
AB  - The international randomised targeted intraoperative radiotherapy (TARGIT) trial
      has demonstrated evidence of non-inferiority between the novel technique of
      TARGIT (intra-operative radiotherapy with Intrabeam((r))) and conventional
      external beam radiotherapy (EBRT) in women with early breast cancer in terms of
      the primary outcome measure of risk of local relapse within the treated breast.
      Cosmesis is an increasingly important outcome of breast conserving treatment with
      both surgery and radiotherapy contributing to this. It was unknown if the single
      high dose of TARGIT may lead to damaging fibrosis and thus impair cosmesis
      further, so we objectively evaluated the aesthetic outcome of patients within the
      TARGIT randomised controlled trial. We have used an objective assessment tool for
      evaluation of cosmetic outcome. Frontal digital photographs were taken at
      baseline (before TARGIT or EBRT) and yearly thereafter for up to 5 years. The
      photographs were analysed by BCCT.core, a validated software which produces a
      composite score based on symmetry, colour and scar. 342 patients were assessed,
      median age at baseline 64 years (IQR 59-68). The scores were dichotomised into
      Excellent and Good (EG), and Fair and Poor (FP). There were statistically
      significant increases in the odds of having an outcome of EG for patients in the
      TARGIT group relative to the EBRT group at year 1 (OR 2.07, 95 % CI 1.12-3.85, p
      = 0.021) and year 2 (OR 2.11, 95 % CI 1.0-4.45, p = 0.05). Following a totally
      objective assessment in a randomised setting, the aesthetic outcome of patients
      demonstrates that those treated with TARGIT have a superior cosmetic result to
      those patients who received conventional external beam radiotherapy. 

PMID- 23877342
TI  - A realistic model under which the genetic code is optimal.
AB  - The genetic code has a high level of error robustness. Using values of
      hydrophobicity scales as a proxy for amino acid character, and the mean square
      measure as a function quantifying error robustness, a value can be obtained for a
      genetic code which reflects the error robustness of that code. By comparing this
      value with a distribution of values belonging to codes generated by random
      permutations of amino acid assignments, the level of error robustness of a
      genetic code can be quantified. We present a calculation in which the standard
      genetic code is shown to be optimal. We obtain this result by (1) using recently
      updated values of polar requirement as input; (2) fixing seven assignments (Ile,
      Trp, His, Phe, Tyr, Arg, and Leu) based on aptamer considerations; and (3) using
      known biosynthetic relations of the 20 amino acids. This last point is reflected
      in an approach of subdivision (restricting the random reallocation of assignments
      to amino acid subgroups, the set of 20 being divided in four such subgroups). The
      three approaches to explain robustness of the code (specific selection for
      robustness, amino acid-RNA interactions leading to assignments, or a slow growth
      process of assignment patterns) are reexamined in light of our findings. We offer
      a comprehensive hypothesis, stressing the importance of biosynthetic relations,
      with the code evolving from an early stage with just glycine and alanine, via
      intermediate stages, towards 64 codons carrying todays meaning. 

PMID- 23877343
TI  - Biological intuition in alignment-free methods: response to Posada.
AB  - A recent editorial in Journal of Molecular Evolution highlights opportunities and
      challenges facing molecular evolution in the era of next-generation sequencing.
      Abundant sequence data should allow more-complex models to be fit at higher
      confidence, making phylogenetic inference more reliable and improving our
      understanding of evolution at the molecular level. However, concern that
      approaches based on multiple sequence alignment may be computationally infeasible
      for large datasets is driving the development of so-called alignment-free methods
      for sequence comparison and phylogenetic inference. The recent editorial
      characterized these approaches as model-free, not based on the concept of
      homology, and lacking in biological intuition. We argue here that alignment-free
      methods have not abandoned models or homology, and can be biologically intuitive.

PMID- 23877344
TI  - Characteristics of MHC class I genes in house sparrows Passer domesticus as
      revealed by long cDNA transcripts and amplicon sequencing.
AB  - In birds the major histocompatibility complex (MHC) organization differs both
      among and within orders; chickens Gallus gallus of the order Galliformes have a
      simple arrangement, while many songbirds of the order Passeriformes have a more
      complex arrangement with larger numbers of MHC class I and II genes. Chicken MHC
      genes are found at two independent loci, classical MHC-B and non-classical MHC-Y,
      whereas non-classical MHC genes are yet to be verified in passerines. Here we
      characterize MHC class I transcripts (alpha1 to alpha3 domain) and perform
      amplicon sequencing using a next-generation sequencing technique on exon 3 from
      house sparrow Passer domesticus (a passerine) families. Then we use phylogenetic,
      selection, and segregation analyses to gain a better understanding of the MHC
      class I organization. Trees based on the alpha1 and alpha2 domain revealed a
      distinct cluster with short terminal branches for transcripts with a 6-bp
      deletion. Interestingly, this cluster was not seen in the tree based on the
      alpha3 domain. 21 exon 3 sequences were verified in a single individual and the
      average numbers within an individual were nine and five for sequences with and
      without a 6-bp deletion, respectively. All individuals had exon 3 sequences with
      and without a 6-bp deletion. The sequences with a 6-bp deletion have many
      characteristics in common with non-classical MHC, e.g., highly conserved amino
      acid positions were substituted compared with the other alleles, low nucleotide
      diversity and just a single site was subject to positive selection. However,
      these alleles also have characteristics that suggest they could be classical,
      e.g., complete linkage and absence of a distinct cluster in a tree based on the
      alpha3 domain. Thus, we cannot determine for certain whether or not the alleles
      with a 6-bp deletion are non-classical based on our present data. Further
      analyses on segregation patterns of these alleles in combination with dating the
      6-bp deletion through MHC characterization across the genus Passer may solve this
      matter in the future.

PMID- 23877345
TI  - From AR to c-Met: androgen deprivation leads to a signaling pathway switch in
      prostate cancer cells.
AB  - Elucidating the role of androgen deprivation in the transition from androgen
      dependence to independence may enable the development of more specific
      therapeutic strategies against prostate cancer. Our previous in vitro model was
      employed to further assess the effects of continuous androgen-deprivation on
      prostate cancer cells (LNCaP) with respect to both androgen receptor (AR) and c
      Met expression. The results indicated that long-term androgen deprivation
      resulted in a signaling pathway switch from AR to c-Met in androgen-sensitive
      cells, which was confirmed by immunofluorescence imaging and western blot
      analysis. This signaling pathway switch may be predictive of a more aggressive
      disease state following androgen deprivation therapy. 

PMID- 23877346
TI  - Cu(II)-catalyzed domino reaction of 2H-azirines with diazotetramic and
      diazotetronic acids. Synthesis of 2-substituted 2H-1,2,3-triazoles.
AB  - The Cu(II)-catalyzed addition of two molecules of a 3-aryl-2H-azirine to
      diazotetramic or diazotetronic acids proceeds as a domino reaction with the
      formation of 1,2,3-triazole derivatives with ortho-fused (pyrrolo[3,4-b]pyrrol or
      furo[3,4-b]pyrrol) and spiro-cyclic (1-oxa-4,7-diazaspiro[4.4]nonane or 1,7-dioxa
      4-azaspiro[4.4]nonane) substituents at the N2 position. The disclosed reaction is
      a new type of formation of a 1,2,3-triazole ring from (N-N) and (C-C-N) building
      blocks.

PMID- 23877347
TI  - Chronic pain and quality of life after transinguinal preperitoneal (TIPP)
      inguinal hernia repair: a few tips on TIPP.

PMID- 23877348
TI  - A randomized, double-blind, controlled trial comparing rifaximin plus lactulose
      with lactulose alone in treatment of overt hepatic encephalopathy.
AB  - OBJECTIVES: Hepatic encephalopathy (HE) is associated with poor prognosis in
      cirrhosis. Drugs used in the treatment of HE are primarily directed at the
      reduction of the blood ammonia levels. Rifaximin and lactulose have shown to be
      effective in HE. We evaluated the efficacy and safety of rifaximin plus lactulose
      vs. lactulose alone for treatment of overt HE. METHODS: In this prospective
      double-blind randomized controlled trial, 120 patients with overt HE were
      randomized into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63)
      and group B (lactulose (n=57) plus placebo). The primary end point was complete
      reversal of HE and the secondary end points were mortality and hospital stay.
      RESULTS: A total of 120 patients (mean age 39.4+/-9.6 years; male/female ratio
      89:31) were included in the study. 37 (30.8%) patients were in Child-Turcotte
      Pugh (CTP) class B and 83 (69.2%) were in CTP class C. Mean CTP score was 9.7+/
      2.8 and the MELD (model for end-stage liver disease) score was 24.6+/-4.2. At the
      time of admission, 22 patients (18.3%) had grade 2, 40 (33.3%) had grade 3, and
      58 (48.3%) had grade 4 HE. Of the patients, 48 (76%) in group A compared with 29
      (50.8%) in group B had complete reversal of HE (P<0.004). There was a significant
      decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose
      and placebo (23.8% vs. 49.1%, P<0.05). There were significantly more deaths in
      group B because of sepsis (group A vs. group B: 7:17, P=0.01), whereas there were
      no differences because of gastrointestinal bleed (group A vs. group B: 4:4,
      P=nonsignificant (NS)) and hepatorenal syndrome (group A vs. group B: 4:7, P=NS).
      Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8+/
      3.4 vs. 8.2+/-4.6 days, P=0.001). CONCLUSION: Combination of lactulose plus
      rifaximin is more effective than lactulose alone in the treatment of overt HE.

PMID- 23877349
TI  - Intraprocedural quality in endoscopic retrograde cholangiopancreatography: a meta
      analysis.
AB  - OBJECTIVES: In 2006, the American College of Gastroenterology (ACG)/the American
      Society for Gastrointestinal Endoscopy (ASGE) Taskforce on Quality in Endoscopy
      published quality indicators for the major gastrointestinal procedures. Our
      primary aim was to use the published literature to assess current endoscopic
      retrograde cholangiopancreatography (ERCP) intraprocedural performance and
      compare it to the targets set by the ACG/ASGE taskforce. Our secondary aim was to
      determine whether performance varies across different health-care settings
      (academic and community), study designs (prospective and retrospective), and
      trainee participation. METHODS: A PubMed and EMBASE literature search from
      1/1/2006 to 2/1/2013 was conducted. Articles were selected based on title,
      abstract, full text, and reporting of success rates for the intraprocedural
      quality indicators. Success rates, represented as numerical proportions, were
      collected from each study. For each success rate, a standard error and a 95%
      confidence interval (CI) was calculated. A random-effects meta-analysis model was
      used to weight each study, and a cumulative, weighted success rate (or effect
      size) for each indicator was determined. Random-effects meta-regression was then
      used to examine the impact of study setting, design, and trainee involvement on
      each quality indicator. RESULTS: A total of 8,005 articles were initially
      retrieved. Following the application of predefined criteria, 52 articles
      remained. The cumulative, weighted bile duct cannulation success rate was 89.3%
      (95% CI 0.866-0.919); pancreatic duct cannulation was 85.0% (95% CI 0.813-0.886);
      precut utilization rate was 10.5% (95% CI 0.087-0.123); common bile duct stone
      extraction rate was 88.3% (95% CI 0.825-0.941); and the rate of successful
      biliary stenting below the common bile duct bifurcation was 97.5% (95% CI 0.967
      0.984). Subgroup analysis with meta-regression showed no statistically
      significant differences between academic and community settings, prospective and
      retrospective study designs, and trainee participation on success across bile
      duct cannulation, precut utilization, and common bile duct stone extraction
      (insufficient observations/variance for pancreatic duct cannulation and biliary
      stent placement). CONCLUSIONS: ERCP intraprocedural quality is in good standing.
      On the basis of this analysis, the two targets that could be potentially revised
      are precut utilization and biliary stenting. This analysis was confined to the
      published literature and therefore, in general, reflects the ERCP performance of
      institutions, primarily academic, that are conducting clinical research. Thus, it
      is difficult to generalize this performance assessment to the broader ERCP
      community as a whole.

PMID- 23877350
TI  - The 22/11 risk prediction model: a validated model for predicting 30-day
      mortality in patients with cirrhosis and spontaneous bacterial peritonitis.
AB  - OBJECTIVES: Clinicians do not have a validated tool for estimating the short-term
      mortality associated with spontaneous bacterial peritonitis (SBP). Accurate
      prognosis assessment is important for risk stratification and for individualizing
      therapy. We aimed therefore to develop and validate a model for the prediction of
      30-day mortality in SBP patients receiving standard medical treatment
      (antibiotics and if indicated by guidelines, intravenous albumin therapy).
      METHODS: We retrospectively identified SBP patients treated at a tertiary care
      center between 2003 and 2011 (training set). Multivariate regression modeling and
      receiver operating characteristic (ROC) curves were utilized for statistical
      analysis. An external data set of 109 SBP patients was utilized for validation.
      RESULTS: Of the 184 patients in the training set, 66% were men with a median age
      of 55 years, a median MELD (Model for End-Stage Liver Disease) score of 20, and a
      30-day mortality of 27%. Peripheral blood leukocyte count >=11*109 cells/l (odds
      ratio (OR) 2.5; 95% confidence interval CI: 1.2-5.2) and MELD score >=22 (OR 4.6;
      95% CI: 2.3-9.6) were independent predictors of 30-day mortality. Patients with
      neither, one, or both variables had 30-day mortality rates of 8%, 32%, and 52%,
      respectively. The findings in the validation set mirrored the training set.
      CONCLUSIONS: In cirrhotic patients with SBP receiving standard therapy, MELD
      score >=22 and peripheral blood leukocyte count >=11*109 cells/l are validated
      independent predictors of mortality. The mortality in a patient without either
      poor prognostic variable is <=10% and with both variables is >=50%. Trials aiming
      to reduce mortality should target patients in the moderate-risk to high-risk
      groups.

PMID- 23877351
TI  - ACG clinical guideline: diagnosis and management of achalasia.
AB  - Achalasia is a primary motor disorder of the esophagus characterized by
      insufficient lower esophageal sphincter relaxation and loss of esophageal
      peristalsis. This results in patients' complaints of dysphagia to solids and
      liquids, regurgitation, and occasional chest pain with or without weight loss.
      Endoscopic finding of retained saliva with puckered gastroesophageal junction or
      barium swallow showing dilated esophagus with birds beaking in a symptomatic
      patient should prompt appropriate diagnostic and therapeutic strategies. In this
      ACG guideline the authors present an evidence-based approach in patients with
      achalasia based on a comprehensive review of the pertinent evidence and
      examination of relevant published data. 

PMID- 23877352
TI  - Large-scale survey of gut microbiota associated with MHE Via 16S rRNA-based
      pyrosequencing.
AB  - OBJECTIVES: Elucidating the minimal hepatic encephalopathy (MHE)-associated gut
      microbiome may help in predicting and lowering the high risk for MHE in patients
      with cirrhosis. METHODS: Twenty-six MHE patients were recruited and screened from
      among those with liver cirrhosis without overt hepatic encephalopathy as defined
      by abnormality seen on two test modalities: number connection test part A and the
      digit symbol test. Using 26 MHE-matched normal relatives and 25 cirrhotic
      patients without MHE as controls, by means of 16S ribosomal RNA (rRNA)-based
      pyrosequencing, we examined and analyzed 241,622 bacterial 16S rDNA gene
      sequences from feces of 77 subjects. RESULTS: Using multiple comparative
      analyses, our results found the continuous overrepresentation of two bacterial
      families, Streptococcaceae and Veillonellaceae, in cirrhotic patients with and
      without MHE, compared with normal individuals. In addition, we also discovered an
      MHE-unique interplay pattern of gut microbiota largely influenced by the members
      of those two families. Following these findings, we further revealed that gut
      urease-containing bacteria Streptococcus salivarius was absent in the normal
      group but was present in cirrhotic patients with and without MHE. The abundance
      of S. salivarius was significantly higher in cirrhotic patients with MHE than in
      those without (P=0.030), and the change in the amount of this bacteria was
      positively correlated with ammonia accumulation (R=0.58, P=0.003) in cirrhotic
      patients with MHE but not in those without. CONCLUSIONS: Gut microbiota dysbiosis
      may be associated with the presence of MHE in cirrhotic patients, in particular
      with ammonia-increasing phenotype in MHE. Gut ammonia-increasing bacteria S.
      salivarius might be expected to be a potential biomarker of ammonia-lowering
      therapies in cirrhotic patients with MHE.

PMID- 23877353
TI  - First total synthesis of (-)-sinularianin B.
AB  - The first enantioselective total synthesis of (-)-sinularianin B, a structurally
      unique sesquiterpenoid isolated from the Formosan soft coral Sinularia sp., has
      been accomplished in 16 steps with 39.5% overall yield. Key transformations
      include formation of a cyclopentane possessing a tertiary hydroxy group via a
      tandem intermolecular-intramolecular alkylation involving a 5-endo cyclization.

PMID- 23877354
TI  - Absorbed fractions for alpha particles in ellipsoidal volumes.
AB  - Internal dosimetry of alpha particles is gaining attention due to the increasing
      applications in cancer treatment and also for the assessment of environmental
      contamination from radionuclides. We developed a Monte Carlo simulation in GEANT4
      in order to calculate the absorbed fractions for monoenergetic alpha particles in
      the energy interval between 0.1 and 10 MeV, uniformly distributed in ellipsoids
      made of soft tissue. For each volume, we simulated a spherical shape, three
      oblate and three prolate ellipsoids, and one scalene shape. For each energy and
      for every geometrical configuration, an analytical relationship between the
      absorbed fraction and a 'generalized radius' was found; and the dependence of the
      fit parameters on the alpha energy is discussed and fitted by parametric
      functions. With the proposed formulation, the absorbed fraction for alpha
      particles in the energy range explored can be calculated for volumes and for
      ellipsoidal shapes of practical interest. This method can be applied to the
      evaluation of absorbed fraction from alpha-emitting radionuclides. The
      contribution to the deposited energy coming from electron and photon emissions
      can be accounted for exploiting the specific formulations previously introduced.
      As an example of application, the dosimetry of (213)Bi and its decay chain in
      ellipsoids is reported. 

PMID- 23877356
TI  - Appropriate use guidelines in echocardiography and beyond.

PMID- 23877357
TI  - Children's objective physical activity by location: why the neighborhood matters.
AB  - Knowledge of where children are active may lead to more informed policies about
      how and where to intervene and improve physical activity. This study examined
      where children aged 6-11 were physically active using time-stamped accelerometer
      data and parent-reported place logs and assessed the association of physical
      activity location variation with demographic factors. Children spent most time
      and did most physical activity at home and school. Although neighborhood time was
      limited, this time was more proportionally active than time in other locations
      (e.g., active 42.1% of time in neighborhood vs. 18.1% of time at home). Children
      with any neighborhood-based physical activity had higher average total physical
      activity. Policies and environments that encourage children to spend time
      outdoors in their neighborhoods could result in higher overall physical activity.

PMID- 23877358
TI  - Regulation of homocysteine metabolism by Mycobacterium tuberculosis S
      adenosylhomocysteine hydrolase.
AB  - Mycobacterium tuberculosis modulates expression of various metabolism-related
      genes to adapt in the adverse host environment. The gene coding for M.
      tuberculosis S-adenosylhomocysteine hydrolase (Mtb-SahH) is essential for optimal
      growth and the protein product is involved in intermediary metabolism. However,
      the relevance of SahH in mycobacterial physiology is unknown. In this study, we
      analyze the role of Mtb-SahH in regulating homocysteine concentration in
      surrogate host Mycobacterium smegmatis. Mtb-SahH catalyzes reversible hydrolysis
      of S-adenosylhomocysteine to homocysteine and adenosine and we demonstrate that
      the conserved His363 residue is critical for bi-directional catalysis. Mtb-SahH
      is regulated by serine/threonine phosphorylation of multiple residues by M.
      tuberculosis PknB. Major phosphorylation events occur at contiguous residues
      Thr219, Thr220 and Thr221, which make pivotal contacts with cofactor NAD+.
      Consequently, phosphorylation negatively modulates affinity of enzyme towards
      NAD+ as well as SAH-synthesis. Thr219, Thr220 and Thr221 are essential for enzyme
      activity, and therefore, responsible for SahH-mediated regulation of
      homocysteine.

PMID- 23877359
TI  - One hundred fold increase in current carrying capacity in a carbon nanotube
      copper composite.
AB  - Increased portability, versatility and ubiquity of electronics devices are a
      result of their progressive miniaturization, requiring current flow through
      narrow channels. Present-day devices operate close to the maximum current
      carrying-capacity (that is, ampacity) of conductors (such as copper and gold),
      leading to decreased lifetime and performance, creating demand for new conductors
      with higher ampacity. Ampacity represents the maximum current-carrying capacity
      of the object that depends both on the structure and material. Here we report a
      carbon nanotube-copper composite exhibiting similar conductivity (2.3-4.7 * 10(5)
      S cm(-1)) as copper (5.8 * 10(5) S cm(-1)), but with a 100-times higher ampacity
      (6 * 10(8) A cm(-2)). Vacuum experiments demonstrate that carbon nanotubes
      suppress the primary failure pathways in copper as observed by the increased
      copper diffusion activation energy (~2.0 eV) in carbon nanotube-copper composite,
      explaining its higher ampacity. This is the only material with both high
      conductivity and high ampacity, making it uniquely suited for applications in
      microscale electronics and inverters.

PMID- 23877355
TI  - The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory
      myopathies.
AB  - The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune
      diseases characterized by skeletal muscle weakness, characteristic rashes, and
      other systemic features. In follow-up to our study defining the major clinical
      subgroup phenotypes of JIIM, we compared demographics, clinical features,
      laboratory measures, and outcomes among myositis-specific autoantibody (MSA)
      subgroups, as well as with published data on adult idiopathic inflammatory
      myopathy patients enrolled in a separate natural history study. In the present
      study, of 430 patients enrolled in a nationwide registry study who had serum
      tested for myositis autoantibodies, 374 had either a single specific MSA (n =
      253) or no identified MSA (n = 121) and were the subject of the present report.
      Following univariate analysis, we used random forest classification and exact
      logistic regression modeling to compare autoantibody subgroups. Anti-p155/140
      autoantibodies were the most frequent subgroup, present in 32% of patients with
      juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ
      autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other
      MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti
      Mi-2, were present in only 10% of JIIM patients. Features that characterized the
      anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, "shawl
      sign" rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK)
      levels, and a predominantly chronic illness course. The features that differed
      for patients with anti-MJ antibodies included muscle cramps, dysphonia,
      intermediate CK levels, a high frequency of hospitalization, and a monocyclic
      disease course. Patients with anti-synthetase antibodies had higher frequencies
      of interstitial lung disease, arthralgia, and "mechanic's hands," and had an
      older age at diagnosis. The anti-SRP group, which had exclusively juvenile
      polymyositis, was characterized by high frequencies of black race, severe onset,
      distal weakness, falling episodes, Raynaud phenomenon, cardiac involvement, high
      CK levels, chronic disease course, frequent hospitalization, and wheelchair use.
      Characteristic features of the anti-Mi-2 subgroup included Hispanic ethnicity,
      classic dermatomyositis and malar rashes, high CK levels, and very low mortality.
      Finally, the most common features of patients without any currently defined MSA
      or myositis-associated autoantibodies included linear extensor erythema,
      arthralgia, and a monocyclic disease course. Several demographic and clinical
      features were shared between juvenile and adult idiopathic inflammatory myopathy
      subgroups, but with several important differences. We conclude that juvenile
      myositis is a heterogeneous group of illnesses with distinct autoantibody
      phenotypes defined by varying clinical and demographic characteristics,
      laboratory features, and outcomes. 

PMID- 23877360
TI  - Apoptosis induced by PGC-1beta in breast cancer cells is mediated by the mTOR
      pathway.
AB  - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) coactivator
      1beta (PGC-1beta) is a well-established regulator of mitochondrial biogenesis.
      However, the underlying mechanism of PGC-1beta action remains elusive. This study
      reveals that knockdown of endogenous PGC-1beta by short-hairpin RNA (shRNA) leads
      to a decrease in the expression of mammalian target of rapamycin (mTOR) pathway
      related genes in MDA-MB-231 cells. After knockdown of PGC-1beta, phosphorylation
      of AMP-activated protein kinase (AMPK), phosphorylation of Rictor on Thr1135,
      Raptor and S6 protein was inhibited. However, Akt phosphorylation on Ser473 was
      upregulated and cell apoptosis occurred. In particular, we demonstrate that the
      levels of PGC-1beta and mTOR correlated with overall mitochondrial activity.
      These results provide new evidence that cell apoptosis is orchestrated by the
      balance between several signaling pathways, and that PGC-1beta takes part in
      these events in breast cancer cells mediated by the mTOR signaling pathway. 

PMID- 23877361
TI  - Management of recurrent medulloblastoma in adult patients: a systematic review
      and recommendations.
AB  - Medulloblastoma accounts for almost one-third of pediatric central nervous system
      (CNS) cancers, but is very rare in the adult population. As a result, adult
      patients with medulloblastoma are often treated according to therapies developed
      for children with similarly staged disease at diagnosis, based on the assumption
      that adult and pediatric tumors have similar properties. The purpose of this
      review was to summarize the evidence and to make recommendations for the
      management of recurrent disease in adult patients with medulloblastoma. We
      conducted a systematic literature search to find publications addressing
      treatment of recurrent medulloblastoma in adults. Current treatment strategies
      for adult patients with relapsed medulloblastoma are based on the results of
      retrospective case series and published consensus recommendations, and include
      maximal safe re-resection where possible, combined with chemotherapy and/or re
      irradiation. We describe the results of 13 publications involving 66 adult
      patients treated with high-dose chemotherapy (HDCT) plus stem cell
      transplantation for recurrent medulloblastoma. HDCT with stem cell
      transplantation may be a treatment option for a small proportion of adult
      patients who are unlikely to benefit from conventional chemotherapy and who are
      fit and have their disease recurrence contained within the CNS. Potential cases
      in which stem cell transplantation is being considered should be discussed at a
      multidisciplinary tumor board which includes involvement by hematologic
      oncologists and transplant specialists. 

PMID- 23877362
TI  - Evaluation of mast cells and hypoxia inducible factor-1 expression in meningiomas
      of various grades in correlation with peritumoral brain edema.
AB  - Meningiomas are common primary brain tumors. However, they are often complicated
      by significant peritumoral brain edema, which leads to surgery difficulties and
      prolonged hospitalization. The aim of this study was to evaluate the presence of
      mast cells and expression of hypoxia inducible factor-1 (HIF-1) in correlation
      with the grade of meningioma and presence of peritumoral brain edema.
      Immunohistochemistry was performed with specific antibodies against tryptase
      (mast cells) and HIF-1 in low grade meningiomas (estimated as G1) and high grade
      meningiomas (estimated as G2 or G3). Peritumoral brain edema observed in MRI was
      graded using Steinhoff classification. Tryptase expression was observed in 40.4 %
      low grade meningiomas and in 90 % high grade cases; HIF-1 in 55.7 % low grade and
      in 84 % high grade meningiomas. There was a statistically significant correlation
      between HIF-1 and tryptase expression in both groups (p = 0.003). Presence of
      peritumoral brain edema statistically correlated with tryptase (p = 0.001) and
      HIF-1 expression (p = 0.004). Mast cells as well as hypoxia are involved in
      meningioma progression, and may be associated with the formation of peritumoral
      brain edema leading to surgery complication and recovery. Therefore, they may be
      useful markers in predicting the clinical course of meningioma cases. 

PMID- 23877363
TI  - Detection of EGFRvIII mutant DNA in the peripheral blood of brain tumor patients.
AB  - Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults and
      remains incurable despite multimodal intensive treatment regimens including
      surgical resection, radiation and chemotherapy. EGFRvIII is a truncated
      extracellular mutant of the EGF receptor (EGFR) found in about a third of GBMs.
      It confers enhanced tumorigenic behavior and is associated with chemo- and radio
      resistance. GBM patients testing positive for EGFRvIII have a bleaker prognosis
      than those who do not. Targeting EGFRvIII positive tumors via vaccines or
      antibody-drug-conjugates represents a new challenging therapeutic avenue with
      potential great clinical benefits. In this study, we developed a strategy to
      detect EGFRvIII deletion in the circulating tumor DNA. The overall goal is to
      identify a simple and robust biomarker in the peripheral blood of patients
      diagnosed with GBM in order to follow their disease status while on treatment.
      Thirteen patients were included in this study, three of which were found to carry
      the EGFRvIII deletion. The circulating DNA status for EGFRvIII correlates with
      the analysis performed on the respective tumor samples, and its level seems to
      correlate with the extent of the tumor resection. This semi-quantitative blood
      biomarker may represent a strategy to (1) screen patients for an anti-EGFRvIII
      therapy and (2) monitor the patients' response to treatment. 

PMID- 23877365
TI  - Development and characterization of a new cell line CF from caudal fin of
      knifefish, Chitala chitala (Hamilton-Buchanan).
AB  - A new cell line was successfully obtained from caudal fin tissue of the
      economically important freshwater fish Chitala chitala. The cell line was
      optimally maintained at 28 degrees C in Leibovitz's L-15 supplemented with 20%
      fetal bovine serum (FBS). The effects of temperature and concentration of FBS on
      the growth of CF cells were examined. The CF cell line consisted predominantly of
      fibroblastic-like cells. Moderately low plating efficiencies 8%, 11%, and 17%
      were observed, with CF cell line in L-15 Medium with 20% FBS. Chromosomal
      analysis of the cell line revealed a diploid number of 42 chromosomes in C.
      chitala. Molecular characterization of mitochondrial 16S rRNA and cytochrome
      oxidase subunit I confirmed the origin of the cell line. The cells were
      successfully cryopreserved in liquid nitrogen (-196 degrees C) for 6 mo, and more
      than 85-90% of CF cells were revived.

PMID- 23877364
TI  - Lipopolysaccharide regulates biosynthesis of cystathionine gamma-lyase and
      hydrogen sulfide through Toll-like receptor-4/p38 and Toll-like receptor-4/NF
      kappaB pathways in macrophages.
AB  - Hydrogen sulfide (H2S), formed mainly by the enzyme cystathionine gamma-lyase
      (CSE) in macrophages, is emerging as a novel regulator in inflammation. Although
      elevated production of H2S has been shown in inflammatory processes, the
      underlying molecular mechanism remains to be further elucidated. In this study,
      we compared parallel TLR4 knockout (TLR4(-/-)) mice with their wild-type
      counterparts following lipopolysaccharide (LPS) treatment. It showed that LPS
      increased the expressions of CSE and biosynthesis of H2S in C57BL/6 mice both in
      vivo and in vitro. However, the effects of LPS were not present in TLR4(-/-)
      mice, indicating the crucial role of TLR4 in LPS-induced expression of CSE and
      biosynthesis of H2S. We subsequently used JNK inhibitor, P38 inhibitor, and ERK
      inhibitor to block the downstream MAPK pathways of TLR4 in macrophages, and found
      that LPS-induced CSE expression and H2S synthesizing activity were inhibited by
      pretreatment with the p38 inhibitor. Similarly, the NF-kappaB inhibitor (BAY 11
      7082) reversed the effects of LPS. These results suggest that LPS increases the
      biosynthesis of CSE and H2S in macrophages mainly in a TLR4-p38-dependent and TLR
      4-NF-kappaB-dependent manner. These findings expand our knowledge of H2S
      biosynthesis during inflammation and provide a foundation for the development of
      novel H2S-based therapies. 

PMID- 23877366
TI  - Reply to letter: "The balance of risk score for allocation in liver
      transplantation".

PMID- 23877369
TI  - A computer study and photoelectric property analysis of potassium-doped lithium
      niobate single crystals.
AB  - First-principles theory was used to design a potassium-doped lithium niobate
      single crystal. The structural, electronic, optical and ferroelectric properties
      of the potassium-doped LiNbO3 single crystal model have been investigated using a
      generalized gradient approximation within density functional theory. It was found
      that substitution with potassium drastically changed the optical and electronic
      nature of the crystal and that the band gap slightly decreases. A series of
      LiNbO3 single crystals doped with x mol% K (x = 0, 3, 6, 9, 12 mol%) were
      successfully grown using the Czochralski method. The crystals were characterized
      using powder X-ray diffraction, UV-vis-infrared absorption spectroscopy and a
      ferroelectric property test. The experimental test results were consistent with
      the calculated predictions. 

PMID- 23877368
TI  - Exercise capacity and ventilatory response during exercise in COPD patients with
      and without beta blockade.
AB  - BACKGROUND: Although beta blockade (BB) in patients with chronic obstructive
      pulmonary disease (COPD) does not show signs of worsening pulmonary function or
      respiratory symptoms, the effects on cardiopulmonary exercise testing (CPET)
      remain unclear. The aim of this study was to determine whether BB affects
      exercise capacity, gas exchange, and hemodynamic responses in patients with COPD.
      METHODS: Twenty-four COPD subjects on BB were matched to 24 COPD subjects without
      BB according to age, gender, body mass index, and severity of COPD. All subjects
      underwent resting pulmonary function and symptom-limited CPET. RESULTS: Comparing
      COPD patients with and without BB revealed that percent peak oxygen consumption
      and VE/VCO2 nadir were not significantly different (45 +/- 16 vs. 51 +/- 23 %, p
      = 0.30, and 35.1 +/- 8.5 vs. 36.2 +/- 11.6 %, p = 0.69). Systolic blood pressure
      and heart rate at peak exercise were significantly decreased in COPD patients
      with BB (168 +/- 16 vs. 185 +/- 20 mmHg, and 109 +/- 16 vs. 122 +/- 14 bpm,
      respectively, p < 0.05). CONCLUSION: Exercise capacity and gas exchange remain
      unaffected in patients with COPD in the presence of BB, although heart rate and
      blood pressure are lower. These findings imply that BB does not adversely affect
      functional capacity in patients with COPD.

PMID- 23877367
TI  - Mild obesity is protective after severe burn injury.
AB  - OBJECTIVE: To assess the impact of obesity on morbidity and mortality in severely
      burned patients. BACKGROUND: Despite the increasing number of people with
      obesity, little is known about the impact of obesity on postburn outcomes.
      METHODS: A total of 405 patients were prospectively enrolled as part of the
      multicenter trial Inflammation and the Host Response to Injury Glue Grant with
      the following inclusion criteria: 0 to 89 years of age, admitted within 96 hours
      after injury, and more than 20% total body surface area burn requiring at least 1
      surgical intervention. Body mass index was used in adult patients to stratify
      according to World Health Organization definitions: less than 18.5 (underweight),
      18.5 to 29.9 (normal weight), 30 to 34.9 (obese I), 35 to 39.9 (obese II), and
      body mass index more than 40 (obese III). Pediatric patients (2 to <=18 years of
      age) were stratified by using the Centers for Disease Control and Prevention and
      World Health Organization body mass index-for-age growth charts to obtain a
      percentile ranking and then grouped as underweight (<5th percentile), normal
      weight (5th percentile to <95th percentile), and obese (>=95th percentile). The
      primary outcome was mortality and secondary outcomes were clinical markers of
      patient recovery, for example, multiorgan function, infections, sepsis, and
      length of stay. RESULTS: A total of 273 patients had normal weight, 116 were
      obese, and 16 were underweight; underweight patients were excluded from the
      analyses because of insufficient patient numbers. There were no differences in
      primary and secondary outcomes when normal weight patients were compared with
      obese patients. Further stratification in pediatric and adult patients showed
      similar results. However, when adult patients were stratified in obesity
      categories, log-rank analysis showed improved survival in the obese I group and
      higher mortality in the obese III group compared with obese I group (P < 0.05).
      CONCLUSIONS: Overall, obesity was not associated with increased morbidity and
      mortality. Subgroup analysis revealed that patients with mild obesity have the
      best survival, whereas morbidly obese patients have the highest mortality.
      (NCT00257244).

PMID- 23877370
TI  - Competence, risk, and resilience in military families: conceptual commentary.
AB  - This commentary highlights conceptual themes in the opening section of this
      special issue on military families in relation to a new synthesis of
      developmental systems theory that emerged from developmental, ecological, and
      family systems theory, as well as developmental psychopathology and
      risk/resilience frameworks. Articles in this special issue draw on these concepts
      to characterize and guide the burgeoning research on military families. This
      perspective emphasizes that multiple dynamic systems interact across levels to
      shape individual development, as well as the function of families and military
      units. Developmental timing is important for understanding how challenges of
      military life may impact individuals and families. Cascade effects are noted,
      where stress experienced by one family or service member can influence the
      function of other individuals or larger systems. Capacity for resilience is
      distributed across systems, including families and cultures, as well as resources
      or supports provided by military organizations to foster adaptive responses or
      recovery. These systems include schools and educational programs that play key
      roles in fostering and supporting resilience for children. Overall, developmental
      system concepts have considerable utility for guiding research with military
      families, particularly in regard to promoting resilience. Moreover, lessons
      learned from military families and programs may have much broader implications
      for many other nonmilitary children, families, and organizations that share
      similar goals and challenges. 

PMID- 23877373
TI  - Quality assurance of electron beams using a Varian electronic portal imaging
      device.
AB  - The feasibility of utilizing an electronic portal imaging device (EPID) for the
      quality assurance of electron beams was investigated. This work was conducted on
      a Varian 2100iX machine equipped with an amorphous silicon (aS1000) portal
      imager. The linearity of the imager pixel response as a function of exposed dose
      was first confirmed. The short-term reproducibility of the EPID response to
      electron beams was verified. Low (6 MeV), medium (12 MeV) and high (20 MeV)
      energies were tested, each along with small (6 * 6 cm(2)), medium (10 * 10 cm(2))
      and large (20 * 20 cm(2)) applicators. Acquired EPID images were analyzed using
      an in-house MATLAB code for radiation field size, penumbra, symmetry and
      flatness. Field sizes and penumbra values agreed with those from film dosimetry
      to within 1 mm. Field symmetry and flatness constancies were measured over a
      period of three weeks. The results indicate that EPID can be used for routine
      quality assurance of electron beams.

PMID- 23877372
TI  - MicroRNA-126 inhibits osteosarcoma cells proliferation by targeting Sirt1.
AB  - Numerous studies have recently suggested that miRNAs contribute to the
      development of various types of human cancer as well as to their proliferation
      and metastasis. The aim of this study was to investigate the functional
      significance of miR-126 and to identify its possible target genes in osteosarcoma
      (OS) cells. Here, we found that expression level of miR-126 was reduced in
      osteosarcoma cells in comparison with the adjacent normal tissues. The enforced
      expression of miR-126 was able to inhibit cell proliferation in U2OS and MG63
      cells, while miR-126 antisense oligonucleotides (antisense miR-126) promoted cell
      proliferation. At the molecular level, our results further revealed that
      expression of Sirt1, a member of histone deacetylase, was negatively regulated by
      miR-126. Therefore, the data reported here demonstrate that miR-126 is an
      important regulator in osteosarcoma, which will contribute to better
      understanding of the important misregulated miRNAs in osteosarcoma cells.

PMID- 23877374
TI  - Back pain in tennis players: a link with lumbar serve kinematics and range of
      motion.
AB  - PURPOSE: This study compared regional lumbar (upper and lower), pelvis, trunk,
      and lower limb kinematics between elite male adolescent players with and without
      a history of low back pain (LBP) during the kick and flat serves as well as
      regional lumbar mobility and serving kinematics relative to the end of range.
      METHODS: Seven players with a history of LBP and confirmed L4/L5 injury and 13
      controls matched for age, height, mass, and performance underwent a three
      dimensional motion analysis during serving trials and lumbar mobility
      assessments. Regional lumbar, pelvis, trunk, and lower limb kinematics were
      compared between pain/no pain and kick/flat serves using a series of 2 * 2 mixed
      model ANOVA, with independent samples t-tests used to compare regional lumbar
      mobility between pain/no pain. RESULTS: The pain group had significantly reduced
      lower lumbar mobility in every plane of motion than the no pain group. The pain
      group demonstrated less right lower lumbar and pelvis/shoulder rotation, greater
      right pelvic tilt, earlier peak right knee extension velocity during the drive
      phase of the tennis serves, and greater lower lumbar and pelvis left rotation,
      upper lumbar left lateral flexion, and anterior pelvis tilt during the forward
      swing phase. All players approached their lumbar end of range during the serve.
      CONCLUSIONS: The results of this investigation suggest that a multidimensional
      LBP management and prevention strategy is required, including the assessment of
      regional spinal mobility, the lower limb and upper limb and spinal kinematics,
      and the integrated work between clinicians and coaches to adapt adverse
      technique.

PMID- 23877371
TI  - Downregulation of microRNA-182 inhibits cell growth and invasion by targeting
      programmed cell death 4 in human lung adenocarcinoma cells.
AB  - Lung cancer is a major cause of cancer death worldwide. Programmed cell death 4
      (PDCD4), an important tumor suppressor, influences transcription and translation
      of multiple genes and modulates different signal transduction pathways. However,
      the upstream regulation of this gene is largely unknown. In our study, we found
      that microRNA-182 (miR-182) was upregulated, whereas PDCD4 was downregulated in
      lung cancer cell lines. We performed methyl thiazolyl tetrazolium and colony
      formation assays to study the influence of miR-182 on proliferation of the lung
      cancer cell lines A549 and SPC-A-1. We also carried out Transwell and wound
      healing assays to investigate the effect of miR-182 on invasion and migration of
      A549 and SPC-A-1. Finally, using the luciferase reporter assay and restore assay,
      we demonstrated that PDCD4 is a direct target of miR-182. These results suggest
      that in lung adenocarcinoma cells, miR-182 plays an oncogenic role as a direct
      negative regulator of PDCD4. 

PMID- 23877375
TI  - CMV amplifies T-cell redeployment to acute exercise independently of HSV-1
      serostatus.
AB  - PURPOSE: Latent cytomegalovirus (CMV) infection has been shown to alter the
      lymphocyte response to acute aerobic exercise, likely due to the corresponding
      increase in exercise-responsive memory CD8(+) T cells. It is unknown if latent
      infection with another herpesvirus, herpes simplex virus 1 (HSV-1), also plays a
      role in shaping the lymphocyte response to exercise. METHODS: Thirty-two men
      (ages 39.3 +/- 14.7 yr) counterbalanced by CMV and HSV-1 serostatus
      (positive/negative) cycled for 30 min at ~80% peak power. Blood sampled before,
      immediately after, and 1 h after exercise was analyzed by flow cytometry for T
      cell subset enumeration. RESULTS: In resting blood, HSV-1(+) had fewer
      lymphocytes, CD4(+) T cells, KLRG1(-) CD28(+) CD4(+) T cells, and CD45RA(
      )CCR7(+)CD4(+) T cells than HSV-1(-), whereas CMV(+) had increased numbers of
      lymphocytes, CD8(+) T cells, KLRG1(+)CD28(-)CD4(+) and CD8(+) T cells, and
      CD45RA(+)CCR7(-)CD8(+) T cells and a lower CD4:CD8 T-cell ratio than CMV(-).
      After exercise, CMV(+) had a greater mobilization of CD8(+) T cells, KLRG1+CD28(
      )CD4+ and CD8(+) T cells, and CD45RA+CCR7(-)CD8+ T cells independently of HSV-1
      serostatus, as well as a greater egress of these subsets 1 h after exercise. HSV
      serostatus did not influence total CD8(+) T-cell response to exercise.
      CONCLUSIONS: The impact of latent CMV infection on the redeployment of T-cell
      subsets with exercise is independent of HSV-1 infection. This is most likely due
      to the unique ability of CMV to alter the composition of the memory T-cell pool
      in favor of exercise-responsive T-cell subsets.

PMID- 23877376
TI  - A submaximal test for the assessment of knee extensor endurance capacity.
AB  - PURPOSE: We aimed to develop an undemanding test for endurance capacity of the
      knee extensor muscles, which can also be applied to frail participants. We
      hypothesized 1) that the first objective indications for peripheral fatigue
      during incremental unilateral repetitive isometric knee extensor contractions
      could be used to assess a fatigue threshold (FT), 2) that torque at FT would
      depend on training status, and 3) that this torque could easily be sustained for
      30 min. METHODS: Five trained and five untrained participants performed 5-min
      bouts of 60 repetitive contractions (3-s on and 2-s off). Torque, set at 25%
      maximal voluntary contraction (MVC), was increased by 5% MVC in subsequent bouts.
      The highest torque for which rectified surface EMG remained stable during the
      bout was defined as the FT. On separate occasions, 30-min bouts were performed at
      and above the FT to assess sustainable torque. Changes in gas exchange
      parameters, HR, and RPE were monitored to corroborate FT. RESULTS: At FT (RPE =
      5.7 +/- 1.7), torque was higher (P < 0.05) in trained (41.4% +/- 5.8% MVC) than
      in untrained participants (30.5% +/- 1.8% MVC). Sustainable torque was ~4% higher
      than (P < 0.05) and significantly related to FT (r(2) = 0.79). When torque was
      increased by 5% MVC, significant increases in rectified surface EMG and VO2 were
      found. CONCLUSIONS: During incremental knee extensor contractions, FT could be
      assessed at a submaximal exercise intensity. FT was higher in trained than in
      untrained participants and was related to exercise sustainability. With the use
      of FT, changes in endurance capacity of single muscle groups can potentially also
      be determined in frail participants for whom exercise performed until exhaustion
      is unwarranted.

PMID- 23877377
TI  - Exercise energy expenditure and postprandial lipemia in girls.
AB  - PURPOSE: This study aimed to examine the effect of 30 and 60 min of moderate
      intensity treadmill walking on postprandial triacylglycerol concentrations
      ([TAG]) in healthy girls. METHODS: Eighteen 10- to 14-yr-old girls (mean +/- SD;
      body mass = 48 +/- 11 kg, body fat = 19.0 +/- 4.6%, peak oxygen uptake [VO2] = 47
      +/- 6 mL.kg.min) completed three 2-d trials in a counterbalanced crossover
      design, each separated by 14 d. On day 1, they rested (CON) or completed 30 min
      (EX30) or 60 min (EX60) of intermittent treadmill exercise at 56% peak VO2,
      inducing energy expenditures of 777 and 1536 kJ (186 and 367 kcal), respectively.
      On day 2, after a 12-h fast, a capillary blood sample was taken for fasting [TAG]
      before a high-fat milkshake (80 kJ.kg(-1) body mass) was consumed. Further blood
      samples were taken hourly over a 6-h postprandial rest period for [TAG]. ANOVA
      and Student's t-tests were used to analyze the data. RESULTS: Fasting [TAG] was
      lower in EX60 than CON (95% confidence interval [CI] = -0.36 to 0.04, effect size
      (ES) = 0.41) and EX30 (95% CI = -0.47 to 0.04, ES = 0.46); all group mean
      concentrations were low (<= 0.90 mmol.L(-1)). The main effect for condition
      revealed differences in postprandial [TAG] over time (ES = 0.36). The EX60 total
      area under the [TAG] versus time curve was lower than CON (95% CI = -2.66 to 
      0.04, ES 0.40) and EX30 (95% CI = -2.11 to 0.15, ES = 0.30); CON and EX30 were
      similar (95% CI = -1.44 to 0.71, ES = 0.10). CONCLUSION: This study demonstrates
      that 60 min but not 30 min of moderate treadmill exercise, with a gross energy
      expenditure of 1536 kJ (367 kcal), attenuated postprandial [TAG] in girls.

PMID- 23877378
TI  - Kinematic and kinetic comparison of running in standard and minimalist shoes.
AB  - PURPOSE: The purpose of this study was to determine whether running in a
      minimalist shoe results in a reduction in ground reaction forces and alters
      kinematics over standard shoe running. The secondary purpose of this study was to
      determine whether within-session accommodation to a novel minimalist shoe occurs.
      METHODS: Subjects were 14 male, rearfoot striking runners who had never run in a
      minimalist shoe. Subjects were tested while running 3.35 m.s(-1) for 10 min on an
      instrumented treadmill in a minimalist and a standard shoe as three-dimensional
      lower extremity kinematics and kinetics were evaluated. Data were collected at
      minute 1 and then again after 10 min of running in both shoe conditions to
      evaluate accommodation to the shoe conditions. RESULTS: Shoe-time interactions
      were not found for any of the variables of interest. Minimalist shoe running
      resulted in no changes in step length (P = 0.967) or in step rate (P = 0.230). At
      footstrike, greater knee flexion (P = 0.001) and greater dorsiflexion angle (P =
      0.025) were noted in the minimalist shoe. Vertical impact peak (P = 0.017) and
      average vertical loading rate (P < 0.000) were greater during minimalist shoe
      running. There were main effects of time as dorsiflexion angle decreased (P =
      0.035), foot inclination at footstrike decreased (P = 0.048), and knee flexion at
      footstrike increased (P = 0.002), yet the vertical impact peak (P = 0.002) and
      average vertical loading rate (P < 0.000) increased. CONCLUSIONS: Running in a
      minimalist shoe appears to, at least in the short term, increase loading of the
      lower extremity over standard shoe running. The accommodation period resulted in
      less favorable landing mechanics in both shoes. These findings bring into
      question whether minimal shoes will provide enough feedback to induce an
      alteration that is similar to barefoot running.

PMID- 23877379
TI  - Reporting hemoglobin A1c: do the units matter?

PMID- 23877380
TI  - Moral distress: an innovative and important subject to study in Brazil :
      commentary on "A reflection on moral distress in nursing together with a current
      application of the concept" by Andrew Jameton.
AB  - There have been recurrent reports of fragilities in the Brazilian health system,
      especially in public institutions. In this commentary, I argue that moral
      distress in nursing in Brazil can still be considered an innovative and important
      subject of study. I also highlight the relevance of engaging educational
      institutions in the development of policies about environmental sustainability.
      It is relevant to continue studying moral distress in nursing and in health care
      generally in order to contribute to the transformation of reality by confronting
      the multiple common situations in the work environment that are recognized by
      many as morally problematic because they infringe upon the rights of people,
      patients, and health care professionals and are an affront to environmental
      health. 

PMID- 23877381
TI  - Laparoscopic pyelolithotomy versus percutaneous nephrolithotomy for a solitary
      renal pelvis stone larger than 3 cm: a prospective cohort study.
AB  - To prospectively compare the outcome of laparoscopic pyelolithotomy (LP) versus
      percutaneous nephrolithotomy (PCNL) in patients with a solitary renal pelvis
      stone larger than 30 mm. We analyzed demographic and perioperative parameters and
      intermediate outcome in 30 adults who underwent transperitoneal LP for solitary
      renal pelvis stone larger than 30 mm (Group I) and compared the results with 30
      patients who underwent PCNL (Group II). The two groups were matched for age, sex
      and stone size (Group I 35.3 +/- 7.33 mm, Group II 36.6 +/- 7.0 mm; P = 0.47).
      Mean operative time was significantly longer in LP group (120.5 +/- 39.94 min
      versus 98.1 +/- 23.28 min; P = 0.01, 95 % CI 5.43-39.23). Stone-free rate after
      LP was significantly higher than after PCNL (100 % versus 76.7 %; P = 0.01). On
      the discharge day, no residual stone was found in LP group, and significant
      residual stone (mean size 9.8 mm, range 7-15 mm) was found in seven patients
      (23.3 %) in PCNL group. After the ancillary procedures, the stone-free rates were
      100 % in LP and 96.6 % in PCNL group at the end of follow-up. The average overall
      treatment cost was significantly lower in LP (683.9 USD versus 815.9 USD; P <
      0.001). Mean postoperative decreases in hemoglobin was similar in both groups.
      Given adequate laparoscopic experience, for patients with a solitary renal pelvis
      stone larger than 3 cm, LP can be considered as an appropriate second choice to
      PCNL. It can be a potentially cost-effective treatment option in terms of one
      session stone-free rate and postoperative complications. However, the potential
      benefits of LP need to be weighed against the more invasive nature of this
      procedure. 

PMID- 23877382
TI  - Effect of the body mass index on outcomes of flexible ureterorenoscopy.
AB  - The aim of the study to compare outcomes of flexible ureterorenoscopy in patients
      with different body mass index (BMI) scores and to explore whether the BMI has an
      effect on outcomes of RIRS. Five hundred and two patients who underwent flexible
      URS in 3 centers between 2008 and 2012 for the management of single upper urinary
      tract calculi were retrospectively reviewed. Patients were categorized as normal
      weight BMI 18.5 to 24.99 kg/m(2), overweight 25 to 29.99 kg/m(2), obese 30 to
      39.99 kg/m(2) and morbid obese >40 kg/m(2).The groups were assessed in terms of
      demographic parameters including age, gender, stone size, intraoperative and
      postoperative variables. The mean patient age was 41.3 +/- 15.51 (18-81) years
      and with an average BMI 26.68 +/- 5.2 kg/m(2) (16.64-55.15 kg/m2). Of the
      patients, 43.2 % had normal weight (NW), 32.2 % were overweight (OW), 21.9 % were
      obese (O) and 2.5 % were morbidly obese (MO). Stone-free rates after single
      procedure in NW, OW, O, MO groups were 60.8, 61.7, 73.6, 61.5 %, respectively (p
      = 0.079). Overall targeted stone-free rates were also similar in four groups
      (88.9, 90.1, 93.6, 90.4 %, p = 0.586). There were no statistically significant
      differences in the frequency of complications and mean hospitalization time among
      the groups (p > 0.05). In conclusion, this study demonstrated that flexible URS
      is a valuable option for the treatment of kidney stone in both obese and non
      obese patients. BMI did not influence the postoperative outcomes. 

PMID- 23877383
TI  - The presence and distribution of alpha adrenergic receptors in human renal pelvis
      and calyces.
AB  - In this study, we aimed to demonstrate the presence of Alpha (alpha) 1 receptors
      and subtypes in human pelvis and calyces, because an agent to facilitate kidney
      stone movement and help decrease pain may be an alpha 1 adrenergic blocker, as
      used in ureteral stones. Twenty patients who applied to our clinic for renal cell
      carcinoma were enrolled to the study. All patients underwent radical nephrectomy.
      After the specimens were removed, excisional biopsies were performed on healthy
      pelvises and calyces. Mean alpha-receptor stain rates in renal pelvis were 2.65
      +/- 0.74, 1.35 +/- 0.81 and 2.9 +/- 0.30 for alpha 1A, 1B and 1D, respectively.
      For calyces, the rates are 2.40 +/- 0.82, 1.50 +/- 0.76 and 2.75 +/- 0.44 for
      alpha 1A, 1B and 1D, respectively (Fig. 1). When the staining patterns were
      compared, alpha 1A and 1D were expressed more in both pelvis and calyces than
      alpha 1B (p < 0.05). After the demonstration of alpha-adrenergic receptors in
      pelvis and calyces of human kidney, it may be helpful in coming up with new
      alternative treatments for patients suffering from kidney stones.

PMID- 23877384
TI  - Regioselective silylation of pyranosides using a boronic acid/Lewis base co
      catalyst system.
AB  - The combination of a boronic acid and a Lewis base, both employed in
      substoichiometric amounts, enables the regioselective silylation of cis-diol
      groups in alkylpyranoside substrates. The proposed mode of activation involves
      the formation of a tetracoordinate adduct that displays enhanced nucleophilicity
      at the boron-bound alkoxide groups. 

PMID- 23877386
TI  - The road ahead for research in Greece.

PMID- 23877385
TI  - Endurance, explosive power, and muscle strength in relation to body mass index
      and physical fitness in greek children aged 7-10 years.
AB  - We aimed to model endurance, explosive power, and muscle strength in relation to
      body mass index (BMI) and physical-fitness tests in Greek children aged 7-10
      years old. In the present large epidemiological study, anthropometric
      measurements and physical-fitness tests (i.e., multistage shuttle run, vertical
      jump, standing long jump, small ball throw and 30-m sprint) from 141,169 children
      were analyzed. Age- and sex-specific normative values for physical fitness tests
      were expressed as tabulated percentiles using the LMS statistical method. The
      correlation coefficients between BMI and performances were negative and
      significant for both sexes (p < .01) in all physical-fitness tests. The only
      exception was a positive correlation between ball throw and BMI (p < .01). Only
      2.9% and 4.0% of boys and girls respectively, passed the upper quartiles in all
      tests. The performance in speed may serve as a predictive factor explaining, at
      least in part, the performance in aerobic endurance and explosive power in
      children aged 7-10 years. The presented population-based data for physical
      fitness tests revealed that only a small percentage of these children are in the
      upper quartiles in all tests. Furthermore, the data suggests that speed
      performance can be used to predict physical fitness. 

PMID- 23877387
TI  - Greece in crisis.

PMID- 23877388
TI  - Tough times for Greek science. Interview by Kosmas Tsakmakidis.

PMID- 23877394
TI  - Nanotwinned metals: It's all about imperfections.

PMID- 23877395
TI  - Valleytronics: Electrons dance in diamond.

PMID- 23877396
TI  - Quasicrystals: Model structures.

PMID- 23877397
TI  - Macromolecular mixing: Entropic templating.

PMID- 23877398
TI  - Nanoparticle self-assembly: Bonding them all.

PMID- 23877399
TI  - Material witness: Colloids get active.

PMID- 23877400
TI  - Huge suppression of charge recombination in P3HT-ZnO organic-inorganic hybrid
      solar cells by locating dyes at the ZnO/P3HT interfaces.
AB  - The charge separation and charge recombination dynamics in P3HT-ZnO and P3HT-dye
      ZnO bulk heterojunction organic-inorganic hybrid solar cells (OIHSCs) prepared by
      a one-pot method were studied using a transient absorption (TA) method, both for
      optical absorption of P3HT in the visible region and for optical absorption of
      SQ36 in the NIR region. In the case of P3HT-ZnO, the charge separation was very
      fast, occurring within 1 ps. On the other hand, high charge recombination between
      electrons in the surface states and/or the conduction band of ZnO and holes in
      P3HT was observed. In the case of P3HT-dye-ZnO, we found that the charge
      recombination could be greatly suppressed by locating the dye at the P3HT/ZnO
      interfaces while maintaining a fast charge separation rate (a few ps to 10 ps).
      Our findings provide one methodology for the design of OIHSCs for improving their
      conversion efficiency, which is to position the dye at the appropriate BHJ
      interfaces. 

PMID- 23877401
TI  - A truncating mutation in B3GNT1 causes severe Walker-Warburg syndrome.
AB  - Walker-Warburg syndrome (WWS) is a genetically heterogeneous form of congenital
      muscular dystrophy with significant brain and ocular involvement. In a multiplex
      consanguineous family with severe WWS phenotype, autozygome-guided sequencing of
      previously reported WWS genes was negative. Exome sequencing followed by
      autozygome filtration revealed a homozygous two-base pair insertion in B3GNT1
      (NM_006876.2:c.821_822insTT), leading to premature truncation of the protein
      (p.Glu274Aspfs*94). Recently, two missense mutations in this gene have been
      reported as probably causal in a family with WWS. This report describes the first
      truncating mutation in B3GNT1 and confirms that this gene, which plays a role in
      alphaDG glycosylation, is a bona fide disease gene in WWS. 

PMID- 23877402
TI  - Anticancer effects of Ac-Phe-Lys-PABC-doxorubicin via mitochondria-centered
      apoptosis involving reactive oxidative stress and the ERK1/2 signaling pathway in
      MGC-803 cells.
AB  - Ac-Phe-Lys-PABC-DOX (PDOX) is a smart doxorubicin (DOX) prodrug designed to
      decrease toxicities while maintaining the potent anticancer effects of DOX. The
      present study aimed to elucidate the molecular mechanisms of action of PDOX using
      MGC-803 gastric cancer cells as a model. The cells were treated with both PDOX
      and DOX, and cytotoxicities, cell cycle analysis, reactive oxygen species (ROS)
      generation, mitochondrial damage and ERK1/2 signaling pathway alterations were
      studied. Abundant cathepsin B expression was observed in the MGC-803 cells, and
      treatment with PDOX and DOX triggered dose-dependent cytotoxicity and resulted in
      a significant reduction in cell viability. IC50 of PDOX and DOX was 14.9 and 4.9
      uM, respectively. Both PDOX and DOX significantly decreased p-ERK1/2, increased
      ROS generation, reduced mitochondrial membrane potential, caused mitochondrial
      swelling and arrested the cell cycle at the G2/S phase, and these effects were
      more pronounced for PDOX than for DOX. PDOX and DOX have different mechanisms of
      action, particularly the mitochondria-centered intrinsic apoptosis involving
      reactive oxidative stress and the ERK1/2 signaling pathway.

PMID- 23877403
TI  - Plasma endothelial protein C receptor influences innate immune response in
      ovarian cancer by decreasing the population of natural killer and TH17 helper
      cells.
AB  - In spite of the growing importance of endothelial protein C receptor/active
      protein C (EPCR/aPC) in tumor biology, their impact on immunological homeostasis
      remains largely unexplored. The objective of this study was to assess whether
      soluble plasma endothelial protein C receptor (sEPCR), which is a regulator of
      circulating aPC, is involved in innate immune response in cancer patients. In the
      Ovcar-3 ovarian cancer line, the role of aPC in secretion of cytokines was
      analyzed. In parallel, in 33 patients, with a diagnosis of ovarian epithelial
      cancer, sEPCR was quantified, blood immune cell phenotypes were determined by
      flow cytometry and plasma cytokines were evaluated using a protein array.
      Spearman's rank correlation coefficients (r) and coefficient significance was
      determined by a statistical hypothesis test (alpha=0.05). Our results show that
      i) aPC induced the secretion of several cytokines in Ovcar-3 cells; ii) 61% of
      patients exhibited a concentration of plasma sEPCR well above the baseline
      (normal plasma level, 100 +/- 28 ng/ml); iii) comparing immune cell phenotypes in
      patients having a normal level of sEPCR with those having a high level of sEPCR,
      it was found that sEPCR levels were correlated with high intensity of cells
      expressing CD45ra, CD3, CD8, CD25 and low intensity of cells expressing CD56 (NK
      cells), CD294 (TH2 cells), IL-2, IL-10, IL-17a (TH17 cells), IL-21 (TH21 cells)
      and CD29 markers (r >= 0.60); and iv) high levels of sEPCR correlate with high
      levels of plasma bioactive proteins such as insulin-like growth factor-2 (IGFII),
      IL-13ralpha, macrophage inflammatory protein (MIP1alpha) and matrix
      metalloproteinase-7 (MMP-7) that have already been proposed as biomarkers for
      ovarian cancer and particularly those with poor prognosis. In conclusion, sEPCR
      produced by ovarian cancer cells, by modulating circulating aPC, influences the
      secretory behavior of tumor cells (cytokines and interleukins). Consequently,
      sEPCR in turn acts on the innate immune response by decreasing effector cells
      such as natural killer and T helper cells (TH2, TH17 and TH21).

PMID- 23877404
TI  - Neurochemical and behavioral characteristics of toxic milk mice: an animal model
      of Wilson's disease.
AB  - Toxic milk mice have an inherited defect of copper metabolism. Hepatic phenotype
      of the toxic milk mice is similar to clinical findings in humans suffering from
      Wilson's disease (WND). In the present study, neurotransmitter system and
      locomotor performance in toxic milk mice was examined to verify the feasibility
      of this animal model for studying neuropathology of WND. Mice aged 2 and 12
      months were used in the experiment. The mice were tested according to rotarod and
      footprint protocols. Monoamine content in brain structures was measured by high
      performance liquid chromatography. In order to detect neuronal loss, expression
      of enzymes specific for dopaminergic [tyrosine hydroxylase (TH)], noradrenergic
      (dopamine beta-hydroxylase) and serotoninergic [tryptophan hydroxylase (TPH)]
      neurons was analyzed by Western blot. The 12-month-old toxic milk mice
      demonstrated impaired locomotor performance in behavioral tests. Motor deficits
      were accompanied by increased copper and serotonin content in different brain
      regions and slight decrease in dopamine concentration in the striatum. The
      expression of TH, dopamine beta-hydroxylase and TPH in the various brain
      structures did not differ between toxic milk mice and control animals. Despite
      differences in brain pathology between humans and rodents, further exploration of
      neuronal injury in toxic milk mice is warranted to broaden the understanding of
      neuropathology in WND.

PMID- 23877407
TI  - eRNAs reach the heart of transcription.
AB  - Recently, various studies shed light on the functional significance of enhancer
      RNAs. Two recent studies published in Nature by Li et al. and Lam et al.
      highlight the importance of these newly characterized RNA molecules and their key
      role in controlling transcriptional programs. 

PMID- 23877406
TI  - New hope for therapy in neurodegenerative diseases.
AB  - The use of genetic screens to define cellular pathways that regulate
      neurodegenerative disease proteins has emerged as a powerful strategy to identify
      potential therapeutic targets for these disorders. Using cross-species genetic
      screens, Park et al. recently identified RAS-MAPK-MSK1 as a cellular pathway that
      modulates levels of the polyglutamine-containing protein ATXN1 and its subsequent
      toxicity in SCA1. 

PMID- 23877408
TI  - Osteoarthritis and osteoporosis: correlations between two clinical entities.

PMID- 23877405
TI  - Viral degradasome hijacks mitochondria to suppress innate immunity.
AB  - The balance between the innate immunity of the host and the ability of a pathogen
      to evade it strongly influences pathogenesis and virulence. The two nonstructural
      (NS) proteins, NS1 and NS2, of respiratory syncytial virus (RSV) are critically
      required for RSV virulence. Together, they strongly suppress the type I
      interferon (IFN)-mediated innate immunity of the host cells by degrading or
      inhibiting multiple cellular factors required for either IFN induction or
      response pathways, including RIG-I, IRF3, IRF7, TBK1 and STAT2. Here, we provide
      evidence for the existence of a large and heterogeneous degradative complex
      assembled by the NS proteins, which we named "NS-degradasome" (NSD). The NSD is
      roughly ~300-750 kD in size, and its degradative activity was enhanced by the
      addition of purified mitochondria in vitro. Inside the cell, the majority of the
      NS proteins and the substrates of the NSD translocated to the mitochondria upon
      RSV infection. Genetic and pharmacological evidence shows that optimal
      suppression of innate immunity requires mitochondrial MAVS and mitochondrial
      motility. Together, we propose a novel paradigm in which the mitochondria, known
      to be important for the innate immune activation of the host, are also important
      for viral suppression of the innate immunity.

PMID- 23877409
TI  - Childhood versus adulthood-onset autoinflammatory disorders: myths and truths
      intertwined.
AB  - Autoinflammatory disorders are characterized by spontaneous episodes of systemic
      inflammation deriving from inherited defects of the innate immune system.
      Childhood is usually the lifetime involved in most inherited autoinflammatory
      disorders, but a moderate number of patients may experience disease onset during
      adulthood. Herein we report our experience in the clinical and genetic approach
      to the diagnosis of autoinflammatory disorders in regard of the first 500
      pediatric and adult patients evaluated during the period 2007-2012 in our Center,
      due to histories of periodically-recurring inflammatory attacks, giving emphasis
      to the differences observed according to patients'age and to the most relevant
      data differentiating child and adult-onset autoinflammatory disorders in the
      medical literature. 

PMID- 23877410
TI  - Manual therapy and therapeutic exercise in the treatment of osteoarthritis of the
      hip: a systematic review.
AB  - This systematic review aimed at investigating the role of therapeutic exercise
      and/or manual therapy in the treatment of hip osteoarthritis (OA). Two
      independent reviewers (AR, CV) searched PubMed, Cinahl, Cochrane Library, PEDro
      and Scopus databases and a third one (SP) was consulted in case of disagreement.
      The research criteria were publication period (from May 2007 to April 2012) and
      publication language (English or Italian). Ten randomized controlled trials
      matched inclusion criteria, eight of which concerning therapeutic exercise and
      two manual therapy. Few good quality studies were found. At mid- and long-term
      follow-up land-based exercises showed insufficient evidence of effectiveness with
      respect to pain and quality of life, but positive results were found for physical
      function. Water exercises significantly reduced fall risk when combined with
      functional exercises. Programs containing progressive and gradual exposure of
      difficult activities, education and exercises promoted better outcomes, higher
      adherence to home program and increased amount of physical activity, especially
      walking. Manual therapy seemed to reduce pain and decrease disability at short
      term. Less use of nonsteroidal anti-inflammatory drugs was statistically
      significant at long-term follow-up in patients treated with manual therapy. The
      relationship between clinical results and radiological grade of OA was not
      investigated. Encouraging results were found in recent literature for manual
      therapy and functional training. Further research is needed to elucidate this
      issue through high-quality trials, especially addressing the aspects that have
      not been thoroughly explored yet, for instance type, amount and scheduling of
      conservative treatment. 

PMID- 23877412
TI  - Bosentan and sildenafil: successful treatment in a sclerodermic patient with
      refractory ulcers.
AB  - Systemic sclerosis is an inflammatory disease of the connective tissue
      characterized by vasculopathy and accumulation of collagen and other components
      of the connective matrix, affecting the skin and internal organs. The appearance
      of skin ulcers as a result of vascular damage is very common in the history of
      the disease. Skin ulcers, painful and slow healing due to atrophy and local
      ischemia, get worse the quality of life of patients. Often, the use of
      conventional therapies (such as calcium channel blockers and prostanoids) does
      not cause the complete healing of the lesions. We report the case of a patient in
      whom therapeutic association between endothelin antagonist (bosentan) and
      phosphodiesterase-V inhibitor (sildenafil) resulted in complete healing of old
      ulcers both to upper and lower limbs and allowed the interruption of intravenous
      therapies. 

PMID- 23877411
TI  - Achievement of sustained deep remission with adalimumab in a patient with both
      refractory ulcerative colitis and seronegative erosive rheumatoid arthritis.
AB  - Inflammatory bowel disease (IBD) is commonly associated with peripheral
      inflammatory arthritis, and it has been estimated that as many as 12% of IBD
      patients report these manifestations. However, rheumatoid arthritis (RA) is
      rarely associated with ulcerative colitis (UC). Among all the biological agents
      available, nine have been currently approved for the treatment of RA. Conversely,
      only Infliximab and recently Adalimumab have been approved for UC. In particular,
      the efficacy of Adalimumab in UC has been demonstrated by both recent randomized
      controlled trials and real-life studies. Moreover, Adalimumab is a well
      established treatment for RA. Herein, we describe a patient with RA and UC
      treated successfully with ADA. 

PMID- 23877413
TI  - Arthroscopic synovectomy and radiosynoviorthesis: a treatment option for
      recurrent arthritis symptoms in patients with pachydermoperiostosis.
AB  - Pachydermoperiostosis as the primary form of hypertrophic osteoarthropathy is a
      rare hereditary disorder with a number of characteristic findings, e.g.
      periosteal hypertrophy, digital clubbing and pachydermia. Further typical
      symptoms include arthritic manifestations in all major joints. Literature review
      showed that therapeutical approaches usually focus on medical therapy alleviating
      chronic polyarthritis by controlling inflammation. In the case presented in this
      report anti-inflammatory therapy appeared to have been insufficient since knee
      arthritis persisted. Arthroscopic synovectomy and radiosynoviorthesis were
      performed consecutively. Postoperative and follow-up examinations indicate that
      this combined therapy reduces pain, increases range of motion and improves
      overall mobility, and is thus of lasting benefit to the patient. 

PMID- 23877414
TI  - Seronegative spondyloarthritis and Darier's disease: more than a casual
      association?
AB  - A 46-year old man, affected by Darier's disease (DD), was seen because of right
      hand pain, later extended to shoulders and ankles. Physical examination showed
      swelling and tenderness of the wrist, metacarpophalangeal and metatarsophalangeal
      joints, of the right Achilles tendon's enthesis and of the left knee, with
      psoriatic-like lesions of the scalp. A diagnosis of seronegative
      spondyloarthritis, supported by HLA-B27 positivity and by the magnetic resonance
      imaging finding of hand synovitis and unilateral sacro-iliitis, was made. The
      correlation between DD, spondyloarthritis and psoriasis has been already
      anecdotally reported. Further observations may clarify if this association is
      more than casual.

PMID- 23877415
TI  - Granulomatosis polyangiitis associated with meningeal involvement: response to
      rituximab therapy after failure of cyclophosphamide.
AB  - Wegener's granulomatosis or granulomatosis polyangiitis associated (GPA) is a
      granulomatous inflammation of the upper and lower respiratory tracts associated
      with necrotising vasculitis of small and medium-sized blood vessels and,
      frequently, necrotising glomerulonephritis. We describe the case of a 37 year old
      female patient presenting with upper respiratory tract involvement, chronic
      rhinosinusitis with green secretions, and bilateral hypoacusia. Ten months later,
      she suffered occipital headache and two episodes of lipothymia associated with
      nausea, photophobia, faintness with visual blurring. Magnetic resonance imaging
      (MRI) revealed aseptic meningitis. The patient was treated with steroids and
      cyclophosphamide without any effect on the neurological symptoms which, however,
      greatly improved after subsequent treatment with rituximab as confirmed by means
      of cerebral MRI. Rituximab is an optimal means of treating cyclophosphamide
      resistant patients with GPA associated with meningeal involvement. 

PMID- 23877416
TI  - Carotid intima media thickness in patients with lupus nephritis: some appraisals.

PMID- 23877417
TI  - The flood pulse as the underlying driver of vegetation in the largest wetland and
      fishery of the Mekong Basin.
AB  - The Tonle Sap is the largest wetland in Southeast Asia and one of the world's
      most productive inland fisheries. The Mekong River inundates the Tonle Sap every
      year, shaping a mosaic of natural and agricultural habitats. Ongoing hydropower
      development, however, will dampen the flood pulse that maintains the Tonle Sap.
      This study established the current underlying relationship among hydrology,
      vegetation, and human use. We found that vegetation is strongly influenced by
      flood duration; however, this relationship was heavily distorted by fire,
      grazing, and rice cultivation. The expected flood pulse alteration will result in
      higher water levels during the dry season, permanently inundating existing
      forests. The reduction of the maximum flood extent will facilitate agricultural
      expansion into natural habitats. This study is the most comprehensive field
      survey of the Tonle Sap to date, and it provides fundamental knowledge needed to
      understand the underlying processes that maintain this important wetland. 

PMID- 23877418
TI  - Appropriate vs clinically useful diagnostic tests.

PMID- 23877419
TI  - An affinity capture involved enzymatic assay for thrombin by using peptide
      aptamers as affinity ligands on magnetic beads.
AB  - Here we present a sensitive and specific assay for thrombin through the affinity
      capture of thrombin with mRNA display generated peptide aptamers on magnetic
      beads and the subsequent thrombin-involved enzymatic reaction. Thrombin at 50 fM
      can be detected. 

PMID- 23877420
TI  - Oxidative atomized spray deposition of electrically conductive poly(3,4
      ethylenedioxythiophene).
AB  - Atomized spray deposition of 3,4-ethylenedioxythiophene monomer in the presence
      of triflic anhydride vapour yields electrically conducting poly(3,4
      ethylenedioxythiophene) layers. 

PMID- 23877421
TI  - Mannose-functionalized dendritic oligothiophenes: synthesis, characterizations
      and studies on their interaction with Concanavalin A.
AB  - We have synthesized and characterized a series of dendritic oligothiophenes
      comprising peripheral mannose functionalities by copper-mediated 1,3-dipolar
      cycloaddition reaction. The hybrids were accessible either by attachment of
      acetyl-protected mannosides at the dendritic oligothiophene or by the direct
      synthesis of the deprotected mannose-oligothiophene conjugates by applying
      heterogeneous reaction conditions. The specific interaction of the functional
      dendritic hybrids with lectin protein Concanavalin A was investigated by
      absorption and fluorescence spectroscopic measurements. An enhancement of
      turbidity was observed due to the specific interaction of the mannosidic
      dendrimer with Con A. The specific interaction was further confirmed by
      fluorescence quenching upon addition of the mannosidic hybrid to Con A. 

PMID- 23877422
TI  - The use of stem cells for pancreatic regeneration in diabetes mellitus.
AB  - The endocrine pancreas represents an interesting arena for regenerative medicine
      and cell therapeutics. One of the major pancreatic diseases, diabetes mellitus is
      a metabolic disorder caused by having an insufficient number of insulin-producing
      beta cells. Replenishment of beta cells by cell transplantation can restore
      normal metabolic control. The shortage in donor pancreata has meant that the
      demand for transplantable beta cells has outstripped the supply, which could be
      met by using alternative sources of stem cells. This situation has opened up new
      areas of research, such as cellular reprogramming and in vivo beta-cell
      regeneration. Pluripotent stem cells seem to be the best option for clinical
      applications of beta-cell regeneration in the near future, as these cells have
      been demonstrated to represent an unlimited source of functional beta cells.
      Although compelling evidence shows that the adult pancreas retains regenerative
      capacity, it remains unclear whether this organ contains stem cells.
      Alternatively, specialized cell types within or outside the pancreas retain
      plasticity in proliferation and differentiation. Cellular reprogramming or
      transdifferentiation of exocrine cells or other types of endocrine cells in the
      pancreas could provide a long-term solution. 

PMID- 23877424
TI  - Epidemiology: Ethnicity, vitamin D and CHD.

PMID- 23877423
TI  - Osteopetrosis: genetics, treatment and new insights into osteoclast function.
AB  - Osteopetrosis is a genetic condition of increased bone mass, which is caused by
      defects in osteoclast formation and function. Both autosomal recessive and
      autosomal dominant forms exist, but this Review focuses on autosomal recessive
      osteopetrosis (ARO), also known as malignant infantile osteopetrosis. The genetic
      basis of this disease is now largely uncovered: mutations in TCIRG1, CLCN7,
      OSTM1, SNX10 and PLEKHM1 lead to osteoclast-rich ARO (in which osteoclasts are
      abundant but have severely impaired resorptive function), whereas mutations in
      TNFSF11 and TNFRSF11A lead to osteoclast-poor ARO. In osteoclast-rich ARO,
      impaired endosomal and lysosomal vesicle trafficking results in defective
      osteoclast ruffled-border formation and, hence, the inability to resorb bone and
      mineralized cartilage. ARO presents soon after birth and can be fatal if left
      untreated. However, the disease is heterogeneous in clinical presentation and
      often misdiagnosed. This article describes the genetics of ARO and discusses the
      diagnostic role of next-generation sequencing methods. The management of affected
      patients, including guidelines for the indication of haematopoietic stem cell
      transplantation (which can provide a cure for many types of ARO), are outlined.
      Finally, novel treatments, including preclinical data on in utero stem cell
      treatment, RANKL replacement therapy and denosumab therapy for hypercalcaemia are
      also discussed.

PMID- 23877426
TI  - Nutrition: Red meat and T2DM---the difficult path to a proof of causality.

PMID- 23877425
TI  - The endocrinology of food intake.
AB  - Many questions must be considered with regard to consuming food, including when
      to eat, what to eat and how much to eat. Although eating is often thought to be a
      homeostatic behaviour, little evidence exists to suggest that eating is an
      automatic response to an acute shortage of energy. Instead, food intake can be
      considered as an integrated response over a prolonged period of time that
      maintains the levels of energy stored in adipocytes. When we eat is generally
      determined by habit, convenience or opportunity rather than need, and meals are
      preceded by a neurally-controlled coordinated secretion of numerous hormones that
      prime the digestive system for the anticipated caloric load. How much we eat is
      determined by satiation hormones that are secreted in response to ingested
      nutrients, and these signals are in turn modified by adiposity hormones that
      indicate the fat content of the body. In addition, many nonhomeostatic factors,
      including stress, learning, palatability and social influences, interact with
      other controllers of food intake. If a choice of food is available, what we eat
      is based on pleasure and past experience. This article reviews the hormones that
      mediate and influence these processes. 

PMID- 23877427
TI  - Myocardial protection in cardiac surgery: a historical review from the beginning
      to the current topics.
AB  - Myocardial protection has become an essential adjunctive measure in cardiac
      surgery for a couple of decades, because since the 1950s, the methods of
      cardioprotection (cardioplegic solutions and related procedures) have been
      improved by the mechanism of myocardial ischemia/reperfusion-induced damage being
      unveiled through the untiring efforts of researchers and clinicians. The concept
      of myocardial protection in cardiac surgery was proposed along with introduction
      of hypothermic crystalloid potassium cardioplegia in the beginning and has been
      diversified by pharmacological additives, blood cardioplegia, temperature
      modulation (warm; tepid), retrograde cardioplegia, controlled reperfusion,
      integrated cardioplegia, and pre-and postconditioning. This historical review
      summarized experimental and clinical studies dealing with the methods and results
      of myocardial protection in cardiac surgery, introducing the newly developed
      concepts for the last decade and the current topics. 

PMID- 23877428
TI  - Interaction of smoothened with integrin-linked kinase in primary cilia mediates
      Hedgehog signalling.
AB  - Here we report that ILK localizes in the mouse primary cilium, a sensory
      organelle required for signalling by the Hedgehog (Hh) pathway. Genetic or
      pharmacological inhibition of ILK blocks ciliary accumulation of the Hh pathway
      effector smoothened (Smo) and suppresses the induction of Gli transcription
      factor mRNAs by SHh. Conditional deletion of ILK or Smo also inhibits SHh-driven
      activation of Gli2 in the embryonic mouse cerebellum. ILK regulation of Hh
      signalling probably requires the physical interaction of ILK and Smo in the
      cilium, and we also show selective cilia-associated interaction of ILK with beta
      arrestin, a known mediator of Smo-dependent signalling. 

PMID- 23877429
TI  - The ribosome triggers the stringent response by RelA via a highly distorted tRNA.
AB  - The bacterial stringent response links nutrient starvation with the
      transcriptional control of genes. This process is initiated by the stringent
      factor RelA, which senses the presence of deacylated tRNA in the ribosome as a
      symptom of amino-acid starvation to synthesize the alarmone (p)ppGpp. Here we
      report a cryo-EM study of RelA bound to ribosomes bearing cognate, deacylated
      tRNA in the A-site. The data show that RelA on the ribosome stabilizes an unusual
      distorted form of the tRNA, with the acceptor arm making contact with RelA and
      far from its normal location in the peptidyl transferase centre. 

PMID- 23877430
TI  - Mapping protein signal pathway interaction in sarcoma bone metastasis: linkage
      between rank, metalloproteinases turnover and growth factor signaling pathways.
AB  - We applied reverse phase protein microarrays technology to map signal pathway
      interactions in a discovery set of 34 soft tissue sarcoma (STS) bone metastases
      compared to healthy bone. Proteins associated with matrix remodeling (MMP),
      adhesion (FAK Y576/577, Syndecan-1), and growth/survival (IGF1R Y1135/1136, PI3K,
      EGFR) were elevated in metastasis compared to normal bone. Linkage between
      Syndecan-1, FAK Y576/577, Shc Y317, and EGFR, IGF Y1135/1136, PI3K/AKT was a
      prominent feature of STS bone metastasis. Elevated linkage between RANKL and
      4EBP1 T37/46, EGFR, IGF1R Y1135/1136, Src Y41, Shc Y317, PI3Kp110gamma was
      associated with short survival. Finally, we tested the hypothesis that signal
      pathway proteins augmented in the STS bone metastasis may provide clues to
      understand the subset of primary STS that metastasize. The most representative
      molecules identified in the discovery set were validated on an independent series
      of 82 primary STS by immunohistochemistry applied to a tissue microarray. The
      goal was to correlate the molecular profile in the primary tumors with a higher
      likelihood of metastasis. Elevation of activated kinase substrate endpoints IRS1
      S612, 4EBP1 T37/46, FAK Y576/577 and loss of Fibronectin, were associated with a
      higher likelihood of metastases. These data indicate that the linkage between
      matrix remodeling, adhesion, and growth signaling may drive STS metastasis and
      can be the basis for prognostic and therapeutic strategies. 

PMID- 23877431
TI  - Sildenafil weaning after discharge in infants with congenital diaphragmatic
      hernia.
AB  - Sildenafil is used to treat pulmonary hypertension (PAH) in infants with
      congenital diaphragmatic hernia (CDH). However, data to guide sildenafil dosing
      and weaning are limited. This is concerning in light of a recent report
      describing increased risk associated with high-dose sildenafil regimens in non
      CDH PAH. A retrospective cohort study of sildenafil usage, dosing, and weaning in
      infants with CDH was conducted at the authors' institution. The findings show
      that 17 % (19/122) of infants were discharged receiving sildenafil at a median
      dose of 8 mg/kg/day (range 2.91-5.78 mg/kg/day). The weaning rate was 0.1
      mg/kg/week (range 0.01-0.5 mg/kg/week). The infants ceased therapy after a median
      of 343 days. At the age of 1 year, 29 % were receiving sildenafil at a dose
      higher than 1.5 mg/kg/day. One infant died of severe PAH. Sildenafil therapy at
      discharge is common in severe CDH. Variation in dosing and weaning rates
      highlights the need for standardized assessment and treatment of PAH after
      discharge to optimize the benefits and minimize the adverse effects of
      sildenafil.

PMID- 23877432
TI  - Physical activity problem-solving inventory for adolescents: development and
      initial validation.
AB  - Youth encounter physical activity barriers, often called problems. The purpose of
      problem solving is to generate solutions to overcome the barriers. Enhancing
      problem-solving ability may enable youth to be more physically active. Therefore,
      a method for reliably assessing physical activity problem-solving ability is
      needed. The purpose of this research was to report the development and initial
      validation of the physical activity problem-solving inventory for adolescents
      (PAPSIA). Qualitative and quantitative procedures were used. The social problem
      solving inventory for adolescents guided the development of the PAPSIA scale.
      Youth (14- to 17-year-olds) were recruited using standard procedures, such as
      distributing flyers in the community and to organizations likely to be attended
      by adolescents. Cognitive interviews were conducted in person. Adolescents
      completed pen and paper versions of the questionnaire and/or scales assessing
      social desirability, self-reported physical activity, and physical activity self
      efficacy. An expert panel review, cognitive interviews, and a pilot study (n =
      129) established content validity. Construct, concurrent, and predictive validity
      were also established (n = 520 youth). PAPSIA is a promising measure for
      assessing youth physical activity problem-solving ability. Future research will
      assess its validity with objectively measured physical activity. 

PMID- 23877433
TI  - Penetrating cardiac injuries. Two case reports.
AB  - INTRODUCTION: Penetrating cardiac injuries is still a diagnostic problem at this
      time. Their management requires immediate surgical intervention and excellent
      surgical critical care postoperatively. PRESENTATION OF CASES: A 15-year old male
      patient was stabbed with a knife to the right chest. The chest radiograph showed
      an haemothorax and the angiography showed an intercostals artery and a right
      auricle injury. After an emergency operation the patient was released home in
      good condition after the toracotomy had healed. A 19-year old male patient was
      stabbed with a knife to the chest more than once. By a left toracotomy we sutured
      the lesion of the left ventricle with multiple single stitch in non-absorbable
      suture, we covered the suture with a sealant. The patient released home in 24
      days. DISCUSSION: Penetrating cardiac injuries is one of the leading cause of
      death from urban violence. To evaluate a thoracic trauma with cardiac injury it's
      clear the use of thorax X-ray and multislice angio-Tc scan. Echocardiography has
      clearly emerged for the diagnosis in patients haemodynamically stable. When the
      patient is haemodynamically unstable the emergency thoracotomy is mandatory.
      CONCLUSION: Despite the high mortality of penetrating cardiac injuries new
      surgical and radiological tecniques may help surgeon to save this patients.

PMID- 23877434
TI  - Giuseppe Moruzzi (1910-1986).

PMID- 23877435
TI  - Alpha2-macroglobulin as a promising biomarker for cerebral small vessel disease
      in acute ischemic stroke patients.
AB  - Alpha2-macroglobulin is a protease inhibitor that enhances procoagulant
      properties via the neutralization of plasmin, plasminogen activators and
      metalloproteinases. Additionally, alpha2-macroglobulin is thought to be involved
      in inflammatory reactions as a carrier protein for interleukin-6 (IL-6). The
      objective of this study was to evaluate the usefulness of alpha2-macroglobulin as
      a biomarker for cerebrovascular diseases. Patients with acute ischemic stroke (n
      = 159; 93 male and 66 female, 71.6 +/- 10.3 years) and patients with no previous
      history of stroke (n = 77; 38 male and 39 female, 70.7 +/- 9.5 years) were
      consecutively enrolled in this study. White matter lesions were assessed via the
      fluid-attenuated inversion recovery image of magnetic resonance images using the
      Fazekas classification. The serum alpha2-macroglobulin levels were measured by
      nephelometry. The serum alpha2-macroglobulin levels at admission in patients with
      acute ischemic stroke were higher than those in the control patients (230.2 +/-
      73.7 vs. 205.0 +/- 55.8 mg/dl, p = 0.009). The serum alpha2-macroglobulin levels
      were positively correlated with age and the severity of the white matter lesions
      (R (2) = 0.048, p < 0.001 and R (2) = 0.058, p < 0.001, respectively), although
      there was no significant association between serum alpha2-macroglobulin levels
      and IL-6 levels. In addition, multivariate analysis showed that increased serum
      alpha2-macroglobulin levels were independently associated with the severity of
      white matter lesions [standardized partial regression coefficient (beta) 0.102, p
      = 0.026]. Increased serum alpha2-macroglobulin levels might be involved in the
      pathophysiology of acute ischemic stroke. Furthermore, serum alpha2-macroglobulin
      levels, which were associated with high-grade white matter lesions, may reflect
      the chronic pathophysiological condition of cerebral small vessel disease.

PMID- 23877437
TI  - Echoing the appropriate use criteria: the role of echocardiography for
      cardiovascular risk assessment of the asymptomatic individual.

PMID- 23877436
TI  - Cerebrospinal fluid biomarkers in Alzheimer's disease, vascular dementia and
      ischemic stroke patients: a critical analysis.
AB  - Vascular factors are thought to contribute to the development of disease
      pathology in neurodegenerative dementia such as Alzheimer's disease (AD). Another
      entity, called vascular dementia (VaD), comprises a less defined group of
      dementia patients having various vascular diseases that especially emerge in the
      elderly population and require valid options for examination and differential
      diagnosis. In the context of a retrospective study, we analyzed the cerebrospinal
      fluid (CSF) biomarkers t-tau, p-tau and Abeta42 of a total of 131 patients with
      AD (n = 47), mild cognitive impairment (MCI) (n = 22), VaD (n = 44) and stroke (n
      = 18). We found a remarkable alteration in CSF biomarker profile in AD, VaD and
      in acute ischemic events. CSF profile in AD patients was altered in a very
      similar way as in stroke patients, without statistical differences. In stroke,
      increase depend largely on size and duration after the initial event. Total tau
      levels were useful to differ between VaD and stroke. Abeta42 decreased in a
      similar way in AD, VaD and stroke and had a trend to lower levels in MCI but not
      in controls. 

PMID- 23877439
TI  - A Na3V2(PO4)3 cathode material for use in hybrid lithium ion batteries.
AB  - A NASICON-structure Na3V2(PO4)3 cathode material prepared by carbothermal
      reduction method is employed in a hybrid-ion battery with Li-involved electrolyte
      and anode. The ion-transportation mechanism is firstly investigated in this
      complicated system for an open three-dimensional framework Na3V2(PO4)3. Ion
      exchange is greatly influenced by the standing time, for example, the 1 hour
      battery presents a specific capacity of 128 mA h g(-1) while the 24 hour battery
      exhibits a value of 148 mA h g(-1) with improved rate and cycling performances
      over existing literature reported Li-ion batteries. In the hybrid-ion system, an
      ion-exchange process likely takes place between the two Na(2) sites in the
      rhombohedral structure. NaLi2V2(PO4)3 could be produced by ion-transportation
      since the Na(+) in the Na(1) site is stationary and the three Na(2) sites could
      be used to accommodate the incoming alkali ions; Li(x)Na(y)V2(PO4)3 would come
      out when the vacant site in Na(2) was occupied depending on the applied voltage
      range. The reported methodology and power characteristics are greater than those
      previously reported.

PMID- 23877438
TI  - CD74-ROS1 fusion transcripts in resected non-small cell lung carcinoma.
AB  - The recent discovery of fusion oncokinases in a subset of non-small cell lung
      carcinomas (NSCLCs) is of considerable clinical interest, since NSCLCs that
      express such fusion oncokinases are reportedly sensitive to kinase inhibitors. To
      better understand the role of recently identified ROS1 and RET fusion oncokinases
      in pulmonary carcinogenesis, we examined 114 NSCLCs for SLC34A2-ROS1, EZR-ROS1,
      CD74-ROS1 and KIF5B-RET fusion transcripts using RT-polymerase chain reaction and
      subsequent sequencing analyses. Although the expression of SLC34A2-ROS1, EZR
      ROS1, or KIF5B-RET fusion transcripts was not detected in any of the cases, the
      expression of CD74-ROS1 fusion transcripts was detected in one (0.9%) of the 114
      NSCLCs. The fusion occurred between exon 6 of CD74 and exon 34 of ROS1 and was an
      in-frame alteration. The mutation was detected in a woman without a history of
      smoking. Histologically, the carcinoma was an adenocarcinoma with a predominant
      acinar pattern; notably, a mucinous cribriform pattern and a solid signet-ring
      cell pattern were also observed in part of the adenocarcinoma. ROS1 protein
      overexpression was immunohistochemically detected in a cancer-specific manner in
      both the primary cancer and the lymph node metastatic cancer. No somatic
      mutations were detected in the mutation cluster regions of the KRAS, EGFR, BRAF
      and PIK3CA genes and the entire coding region of p53 in the carcinoma, and the
      expression of ALK fusion was negative. The above results suggest that CD74-ROS1
      fusion is involved in the carcinogenesis of a subset of NSCLCs and may contribute
      to the elucidation of the characteristics of ROS1 fusion-positive NSCLC in the
      future.

PMID- 23877440
TI  - Hydrogen cyanide production due to mid-size impacts in a redox-neutral N2-rich
      atmosphere.
AB  - Cyanide compounds are amongst the most important molecules of the origin of life.
      Here, we demonstrate the importance of mid-size (0.1-1 km in diameter) hence
      frequent meteoritic impacts to the cyanide inventory on the early Earth.
      Subsequent aerodynamic ablation and chemical reactions with the ambient
      atmosphere after oblique impacts were investigated by both impact and laser
      experiments. A polycarbonate projectile and graphite were used as laboratory
      analogs of meteoritic organic matter. Spectroscopic observations of impact
      generated ablation vapors show that laser irradiation to graphite within an N2
      rich gas can produce a thermodynamic environment similar to that produced by
      oblique impacts. Thus, laser ablation was used to investigate the final chemical
      products after this aerodynamic process. We found that a significant fraction
      (>0.1 mol%) of the vaporized carbon is converted to HCN and cyanide condensates,
      even when the ambient gas contains as much as a few hundred mbar of CO2. As such,
      the column density of cyanides after carbon-rich meteoritic impacts with
      diameters of 600 m would reach ~10 mol/m(2) over ~10(2) km(2) under early Earth
      conditions. Such a temporally and spatially concentrated supply of cyanides may
      have played an important role in the origin of life. 

PMID- 23877441
TI  - The iron-catalyzed construction of 2-aminopyrimidines from alkynenitriles and
      cyanamides.
AB  - Several cycloaddition catalysts and reagents were surveyed for their
      effectiveness toward cyclizing alkynenitriles with cyanamides. Catalytic amounts
      of FeI2, (iPr)PDAI and Zn were found to effectively catalyze the [2+2+2]
      cycloaddition of a variety of cyanamides and alkynenitriles to afford bicyclic 2
      aminopyrimidines. 

PMID- 23877442
TI  - Cytosine containing dipyrimidine sites can be hotspots of cyclobutane pyrimidine
      dimer formation after UVB exposure.
AB  - Exposure to the UV component of sunlight is the principal factor leading to skin
      cancer development. Cyclobutane pyrimidine dimers (CPD) are considered to be the
      most important pre-mutagenic type of DNA damage involved in skin carcinogenesis.
      To better understand the biological mechanisms of UV carcinogenesis, it is
      critical to understand the CPD distribution between the four types of
      dipyrimidine sites. Most of our knowledge regarding CPD distribution comes from
      in vitro studies or from investigations using UVC, even though we are not
      naturally exposed to these UV wavelengths. We exposed normal human fibroblasts
      and purified DNA to UVB. Using ligation-mediated PCR, we quantified the CPD
      formation at 952 dipyrimidine sites among the PGK1 (phosphoglycerate kinase 1),
      JUN, HRAS, KRAS, NRAS and TP53 genes. In cellulo, we found a CPD distribution of
      27 : 27 : 25 : 21 for TT : CC : TC : CT. This distribution is similar to that
      observed in vitro. In the analysed genes, we observed some extremely frequently
      damaged dipyrimidine sites and many of these occurred at potentially frequently
      mutated sites, i.e. at dipyrimidine sites containing cytosine. Also, most of the
      frequently damaged dipyrimidine sites in cellulo that are not frequently damaged
      in vitro are found on TP53 and NRAS. This indicates that many of the frequently
      damaged dipyrimidine sites in cellulo are on genes frequently mutated in skin
      cancer. All these results support the view that CPD are the main UVB-induced
      mutagenic photoproducts and provide evidence of the importance of CPD formation
      at sites containing cytosine.

PMID- 23877443
TI  - Gate effects in a hexagonal zinc-imidazolate-4-amide-5-imidate framework with
      flexible methoxy substituents and CO2 selectivity.
AB  - A new imidazolate-4-amide-5-imidate based MOF, IFP-7, is generated, having
      flexible methoxy groups, which act as molecular gates for guest molecules. This
      allows highly selective CO2 sorption over N2 and CH4 gases. 

PMID- 23877445
TI  - A systematic review and meta-analysis of randomized controlled trials of
      unilateral versus bilateral kyphoplasty for osteoporotic vertebral compression
      fractures.
AB  - BACKGROUND: Kyphoplasty reduces the pain caused by osteoporotic vertebral
      compression fracture (OVCF). Although the procedure is typically carried out
      using a bilateral approach, it is now increasingly performed using a unilateral
      approach because of the concern for long-term adverse effects. However, little
      evidence is available to demonstrate superior safety of the unilateral approach.
      OBJECTIVE: The purpose of this study was to compare the short- and long-term
      safety and efficacy of unilateral vs. bilateral kyphoplasty. STUDY DESIGN: A
      systematic review and meta-analysis of randomized controlled trials. SETTINGS:
      MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and abstracts
      published in the related orthopedic journals were systematically searched up to
      September 2012, using "unilateral kyphoplasty" and "osteoporotic vertebral
      compression fractures" as key words. METHODS: Two investigators independently
      searched and identified relevant reports and abstracts using the PRISMA statement
      criteria. Relevant studies cited by the identified papers were also included. The
      level of evidence was classified as good, fair, and limited (or poor) based on
      the quality of evidence developed by the U.S. Preventive Services Task Force
      (USPSTF). RESULTS: Four randomized controlled trials (RCTs) of 159 cases were
      enrolled. The methodological quality of the articles was determined as moderate.
      We did not find any significant difference between unilateral and bilateral
      kyphoplasty on pain relief, in either short-term or long-term follow-up (P = 0.65
      and P = 0.69, respectively). The rate of adjacent vertebral fracture was not
      statistically different with a P value of 0.88 and 95% CI (confidence intervals)
      of 0.25-3.26. Cement leakage was comparable between unilateral and bilateral
      kyphoplasty (P = 0.56, 95% CI = 0.46-4.26). The loss of vertebral height in long
      term follow-up was not different (P = 0.10, 95% CI = -0.39-4.54). Operation time
      and cement dosage were considerably less for unilateral kyphoplasty (P < 0.01 and
      P < 0.05, respectively). LIMITATIONS: Only 4 RCTs and 159 patients were included
      in this systematic review. Publication bias also existed among the studies
      included. CONCLUSIONS: Both unilateral and bilateral kyphoplasty are effective in
      alleviating the back pain caused by OVCF. Two approaches have the same degree of
      safety. More RCTs are needed to examine the efficacy and adverse reactions of the
      2 approaches.

PMID- 23877444
TI  - Understanding the loss-of-function in a triple missense mutant of DNA polymerase
      beta found in prostate cancer.
AB  - Human DNA polymerase (pol) beta is essential for base excision repair. We
      previously reported a triple somatic mutant of pol beta (p.P261L/T292A/I298T)
      found in an early onset prostate tumor. This mutation abolishes polymerase
      activity, and the wild-type allele was not present in the tumor, indicating a
      complete deficiency in pol beta function. The effect on polymerase activity is
      unexpected because the point mutations that comprise the triple mutant are not
      part of the active site. Herein, we demonstrate the mechanism of this loss-of
      function. In order to understand the effect of the individual point mutations we
      biochemically analyzed all single and double mutants that comprise the triple
      mutant. We found that the p.I298T mutation is responsible for a marked
      instability of the triple mutant protein at 37C. At room temperature the triple
      mutant's low efficiency is also due to a decrease in the apparent binding
      affinity for the dNTP substrate, which is due to the p.T292A mutation.
      Furthermore, the triple mutant displays lower fidelity for transversions in
      vitro, due to the p.T292A mutation. We conclude that distinct mutations of the
      triple pol beta mutant are responsible for the loss of activity, lower fidelity,
      and instability observed in vitro.

PMID- 23877446
TI  - Central sensitization in urogynecological chronic pelvic pain: a systematic
      literature review.
AB  - BACKGROUND: Chronic pelvic pain (CPP) is a complex pain syndrome. Since its
      pathogenesis is still poorly understood and structural alterations in pain
      related brain regions may be present, there is a greater acceptance that
      sensitization of the central nervous system (CNS) plays an important role in the
      development and maintenance of chronicity. OBJECTIVE: The purpose of this study
      is to systematically review the scientific evidence regarding central
      sensitization (CS) in female patients with urogynecological CPP. STUDY DESIGN:
      Systematic review of the literature. METHODS: A systematic literature search was
      conducted in PubMed and Web of Science using different keyword combinations
      related to urogynecological CPP and central sensitization. Full text clinical
      reports addressing CS in adult women with urogynecological CPP were included and
      assessed for methodological quality by 2 independent reviewers. RESULTS: After
      screening for the eligibility, a total of 29 full-text articles with low to good
      methodological quality were retained. All studies were observational, 27 of which
      were case-control and 2 of which were cohorts. Sensitivity of the CNS was
      investigated by using a variety of methods. Although different central mechanisms
      seem to be involved in pain processing, the present evidence suggests
      hyperexcitability of the CNS in patients with urogynecological CPP. Altered brain
      morphology and function, generalized hyperalgesia to different type of stimuli,
      overactive bottom-up nociceptive mechanisms, and autonomic dysregulation were
      established in patients with urogynecological CPP. Nevertheless, diffuse noxious
      inhibitory control seemed normal, and therefore the contribution of an impaired
      endogenous pain inhibition mechanism to CPP requires further study. The same goes
      for the contribution of psychological factors. LIMITATIONS: The level of evidence
      of retained studies is low due to the observational study designs and a wide
      range of diagnoses and assessment methods. CONCLUSION: Although the majority of
      the literature provides evidence for the presence of CS in urogynecological CPP
      with changes in brain morphology/function and sensory function, it is unclear
      whether these changes in central pain processing are secondary or primary to CPP,
      especially since evidence regarding the function of endogenous pain inhibition
      and the role of psychosocial pain facilitation is scarce. Further studies with
      good methodological quality are needed in order to clarify exact mechanisms.

PMID- 23877447
TI  - Vertebral augmentation: update on safety, efficacy, cost effectiveness and
      increased survival?
AB  - Although over 300 articles have been published annually on vertebral augmentation
      in the last 5 years, there remains much debate about a fundamental question - is
      vertebral augmentation a safe and effective treatment to achieve analgesia,
      reduce disability, and improve quality of life in patients with a vertebral
      fracture? In this modern era of evidence-based clinical practice and public
      health care policy and funding, an evidentiary basis is needed to continue to
      perform vertebral augmentation. The aim of this narrative review is to summarize
      the latest and highest quality evidence for efficacy, safety, cost effectiveness,
      and potential survival benefit after vertebroplasty and kyphoplasty. The design,
      major inclusion criteria, primary outcome measures, relevant primary baseline
      characteristics, primary outcomes, relevant secondary outcomes, and limitations
      of prospective multicenter randomized sham-controlled and conservative management
      controlled trials are summarized. Recently published meta-analyses or systematic
      reviews of efficacy that include these recent prospective studies of vertebral
      augmentation are examined. The highest quality procedural safety data relating to
      medical complications, cement leaks, and subsequent vertebral fracture are
      reviewed. Publications from national databases analyzing potential reduction in
      length of hospital stay and reduction in mortality after vertebral augmentation
      are presented. Finally, emerging literature assessing the potential cost
      effectiveness of vertebral augmentation is considered. This narrative review will
      provide interventional pain physicians a summary of the latest and highest
      quality data published on vertebral augmentation. This will allow integration of
      the best available evidence with clinical expertise and patient wishes to make
      the most appropriate evidence-based clinical decisions for patients with
      symptomatic vertebral fracture. 

PMID- 23877448
TI  - Needle position analysis in cases of paralysis from transforaminal epidurals:
      consider alternative approaches to traditional technique.
AB  - BACKGROUND: Transforaminal technique for epidural steroid injections, unlike
      other approaches, is uniquely associated with permanent, bilateral, lower
      extremity paralysis. OBJECTIVE: To review the literature and analyze the reported
      cases of paralysis from lumbar transforaminal epidural steroid injections to
      possibly establish a cause and to prevent this complication. STUDY DESIGN:
      Eighteen cases of paralysis from transforaminal epidural injection have been
      reported. We could analyze the position of the needle within the neural foramen
      based on the available images and/or description among 10 of these 18 cases. Five
      cases were performed with computed tomography guidance and 12 cases were
      performed with fluoroscopic guidance [unknown in one case]. Additionally, other
      variables associated with the procedure, including the technique, were also
      examined. METHODS: Analysis of the needle position in the neural foramen in cases
      of paralysis from transforaminal epidural steroid injections. This analysis is
      based on images and/or description provided in published reports. RESULTS:
      Paralysis in these cases seems to be associated with a well performed traditional
      safe triangle approach with good epidural contrast spreads. Analyzed data shows
      that 77.7% of the time, the needle was in the superior part of the foramen. In
      71.4% of the cases, the needle was in the anterior part of the foramen. This
      coincides with the location of the radicular artery in the foramen. In 22.2%, the
      needle was in the midzone (neither in the superior nor inferior zone). No level
      was spared as this event occurred at every foramen from T12 to S1. Ten of these
      events happened during a left-sided procedure and 8 during a right-sided
      procedure. No relation to this complication was noted when other variables like
      type and size of the needles, side of the injection, local anesthetic, contrast,
      or volume of injectate were taken into consideration. LIMITATIONS: Only 18 cases
      of paralysis from transforaminal epidurals have been reported. Out of these, only
      10 cases included images or descriptions which could be evaluated for our study.
      CONCLUSION: In light of the anatomical and radiological evidence in the
      literature that radicular arteries dwell in the superior part of the foramen and
      along with our needle position analysis, we suggest that the traditional
      technique of placing the needle in the superior and anterior part of the foramen
      must be reexamined. Alternative, safer techniques must be considered, one of
      which is described.

PMID- 23877449
TI  - The current state of endoscopic disc surgery: review of controlled studies
      comparing full-endoscopic procedures for disc herniations to standard procedures.
AB  - BACKGROUND: Neuropathic pain originating from spinal disc herniations is a very
      common problem. The majority of disc surgeries are performed to alleviate this
      pain once conservative measures and targeted injections have failed. Endoscopic
      spinal surgery is increasingly popular because it minimizes access trauma and
      hastens recovery from the intervention. This clinically oriented review evaluates
      controlled studies that investigate the clinical results and the complications of
      full-endoscopic lumbar and cervical procedures for symptomatic disc herniations
      in comparison to a microsurgical standard procedure. This review focuses
      exclusively on modern, full-endoscopic disc surgery irrespective of the specific
      access technique (e.g., interlaminar vs. transforaminal) and irrespective of the
      spinal region. STUDY DESIGN: Comprehensive review of the literature. OBJECTIVE:
      To assess the clinical outcomes and complication rates of full-endoscopic disc
      surgery compared to the microsurgical standard procedures. METHODS: A PubMed and
      Embase search was performed, considering entries up to January 2013. All 504
      results were screened and categorized. Only 4 randomized controlled trials (RCTs)
      and one controlled studies (CS) could finally be considered for evaluation. All 5
      manuscripts were meticulously analyzed with regards to randomization mode,
      inclusion/exclusion criteria, clinical results, and complication rates. RESULTS:
      Overall, the endoscopic techniques had shorter operating times, less blood loss,
      less operative site pain, and faster postoperative rehabilitation/shorter
      hospital stay/faster return to work than the microsurgical techniques. There were
      no significant differences in the main clinical outcome criteria between the
      endoscopic and the microsurgical techniques in any of the trials. All 5 studies
      had fewer complications with the endoscopic technique and this was statistically
      significant in 2 of the studies. One study showed a lower rate of revision
      surgeries requiring arthrodesis with the endoscopic technique. LIMITATIONS: All 5
      studies that could be considered originate from experienced investigators and all
      4 RCTs came from one group. This limits the transferability of their results to
      surgeons less experienced in endoscopic disc surgery. CONCLUSIONS: The studies
      show that full-endoscopic disc surgery can achieve the same clinical results in
      symptomatic cervical and lumbar disc herniations as the microsurgical standard
      techniques. This does not appear to come at the price of higher complication
      rates.

PMID- 23877450
TI  - The effect of lumbar sympathetic ganglion block on gynecologic cancer-related
      lymphedema.
AB  - BACKGROUND: Eighteen to 25% of patients after gynecological cancer treatment
      suffer from lower limb lymphedema (LLL) that decreases the quality of life of
      gynecological cancer survivors. Lumbar sympathetic ganglion block (LSGB) is
      widely used in practice for the evaluation and management of sympathetically
      mediated pain in the lower limbs. Several articles have suggested that
      sympathetic ganglion block could be an effective treatment for lymphedema.
      OBJECTIVES: To investigate the effect of LSGB on patients with secondary
      lymphedema related to the treatment of gynecologic cancer, who do not respond to
      a conservative treatment. STUDY DESIGN: Prospective clinical study. SETTING: A
      single academic medical center, outpatient setting. METHODS: Eighteen patients
      with stage II lower limb lymphedema who did not response to the conservative
      treatment were recruited. The patients underwent fluoroscopy-guided LSGB 3 times
      at 2-week intervals. The circumference of the thigh and calf was measured in the
      upright position at the first visit and 2 weeks after each session of LSGB. The
      pain score of the lower limb was checked at the same time by a numeric rating
      scale (NRS) from 0 to 10. The patients were asked about their satisfaction with
      the procedure at the last follow-up visit. The Wilcoxon signed rank test was used
      for data analysis. Significance was accepted at a P-value less than 0.05/3.
      RESULTS: The circumferences of affected thighs and calves decreased from 56.38 +/
      4.77 and 35.33 +/- 3.51 cm to 54.42 +/- 5.27 and 34.41 +/- 3.35 cm,
      respectively, in a significant manner after 3 consecutive LSGBs (P < 0.05/3). The
      maximal decrease after the third LSGB was 4 cm in the thigh and 2 cm in the calf.
      The pain score also showed a significant decrease after 3 consecutive LSGBs from
      2.17 to 1.28. The tightness and heaviness of the affected limb decreased after
      the first LSGB in 15 patients (83.3%) and after the second LSGB in 2 patients
      (11.1%). Five of 18 patients (27.8%) answered that the result of the LSGB met
      their expectations, 10 (55.6%) answered they would undergo the same treatment for
      the same outcome, 2 (11.1%) answered they did not improve as much as they had
      hoped, and they would not undergo the same treatment for the same outcome, and
      only one patient (5.6%) answered the LSGB showed no effect. LIMITATIONS: This
      study lacks a placebo control group and has only 18 patients. We did not evaluate
      the quality of life of the patients. CONCLUSION: We suggest that LSGB can be one
      of the treatment options for patients suffering from LLL after gynecologic cancer
      treatment. Our result could provide a basis for a randomized controlled trial in
      future investigations. The pain physicians can play an important role as one of
      the multidisciplinary team for a comprehensive treatment of LLL.

PMID- 23877451
TI  - Preliminary results of the clinical effectiveness of percutaneous adhesiolysis
      using a Racz catheter in the management of chronic pain due to cervical central
      stenosis.
AB  - BACKGROUND: Cervical central stenosis (CCS) is a narrowing of the spinal canal
      that can cause mechanical compression of the spinal nerve and roots, leading to
      neck pain and/or radicular pain. Cervical epidural steroid injections are
      commonly used in the treatment of CCS. After failure of epidural steroid
      injections, the next sequential step is percutaneous adhesiolysis with a targeted
      drug delivery. OBJECTIVE: The aim of our study is to evaluate the effectiveness
      of percutaneous cervical epidural adhesiolysis in patients with chronic posterior
      neck pain and upper extremity pain due to CCS. STUDY DESIGN: This was a
      preliminary, prospective study. METHODS: Thirty-nine patients with CCS were
      enrolled and all subjects underwent cervical spine magnetic resonance imaging.
      All patients received percutaneous adhesiolysis and appropriate placement of a
      Racz catheter, followed by an injection of 5 mL of 0.2 % preservative-free
      ropivacaine containing 1,500 units of hyaluronidase and 4 mg of dexamethasone. In
      the recovery room, each patient also received 6 mL of 10% hypertonic sodium
      chloride solution, after which the catheter was removed. Outcome measures were
      obtained using a 5-point patient's satisfaction scale at 2 weeks and at 6 months
      post-treatment. To evaluate treatment effectiveness, we divided the patients into
      2 groups according to their treatment response. LIMITATIONS: Secondary outcomes
      were not measured. The study did not include a long-term follow-up period or
      control group. RESULTS: Improvement designated as reports of moderate pain,
      little pain, and no pain was observed in 30 patients (77.0 %) at 2 weeks and 28
      patients (71.8 %) at 6 months after the procedure. There was no statistically
      significant correlation between pain relief and the severity of CCS. CONCLUSION:
      Percutaneous adhesiolysis utilizing local anesthetic steroids and hypertonic
      sodium chloride solution may be an effective management strategy in patients with
      chronic posterior neck and upper extremity pain due to cervical central spinal
      stenosis, although there is no correlation between therapeutic response and the
      grade of CCS.

PMID- 23877452
TI  - Comparative assessment of different percutaneous endoscopic interlaminar lumbar
      discectomy (PEID) techniques.
AB  - BACKGROUND: Percutaneous endoscopic lumbar discectomy is a common surgical
      treatment for lumbar disc herniation, and percutaneous endoscopic interlaminar
      lumbar discectomy (PEID) is commonly used for direct decompression of L5-S1. Like
      microdiscectomy, recurrence of herniation after endoscopic discectomy is an
      important problem. In this study, we aimed to decrease the recurrence after PEID
      using a new surgical technique. OBJECTIVES: We propose a new surgical technique
      for reducing the recurrence after PEID for lumbar disc herniation. The new
      technique uses annular sealing after fragmentectomy. We compared clinical results
      and recurrent lumbar disc herniation (had radiculopathy and confirmed by MRI)
      between patients who underwent surgery with and without annular sealing during
      PEID. STUDY DESIGN: Retrospective cohort study of patients undergoing PEID.
      METHODS: A total of 224 patients with radiculopathy due to L5-S1 disc herniation
      who were treated by PEID with (91 patients) or without annular sealing (133) were
      included in this study. We compared the demographic characteristics (age, sex,
      height, weight, BMI, smoking status, and occupation), clinical results, and
      recurrence rates between the 2 groups. We classified recurrence according to time
      period (early recurrence <= 6 months, late recurrence > 6 months). RESULTS: The
      study groups were demographically similar, and substantial improvement in
      clinical results was noted. There were 5 recurrences (5.5%) (2 early, 3 late
      recurrences) in the group with annular sealing, and 18 (13.5%) (13 early, 5 late
      recurrences) in the group without annular sealing. Early recurrence rates were
      significantly higher in the group without sealing (2 vs. 13, P = 0.029).
      Increasing age was associated with overall recurrence (P = 0.004) and late
      recurrence (P = 0.008), while operative technique correlated with early
      recurrence (P = 0.026). LIMITATIONS: First, this study incorporates a
      retrospective design. Second, the operations were performed by 2 surgeons.
      Additionally, this is relatively a short-term follow-up study (mean 19.5 +/- 5.0
      months). CONCLUSIONS: Though a learning curve is needed in order to become
      familiar with PEID, recurrence after PEID was associated with advanced age, and
      PEID with annular sealing resulted in lower early recurrence rates than without
      annular sealing. Thus, PEID with annular sealing may be a useful technique for
      reducing early recurrence.

PMID- 23877453
TI  - Computed tomography guidance for spinal intervention: basics of technique,
      pearls, and avoiding pitfalls.
AB  - The utilization of spinal interventional pain techniques has grown rapidly over
      the last decade. However, practitioners use widely different techniques in these
      procedures, particularly in the use of image guidance. The importance of image
      guidance was highlighted by the fact that in recent systematic reviews on
      therapeutic effectiveness of epidural steroid injections and facet joint
      interventions, only studies that used image guidance were included. The choice of
      image guidance remains a matter of physician preference with conventional
      fluoroscopic or Computed Tomography (CT) guidance most common. There are many
      advantages to CT guidance for certain spinal interventional pain procedures,
      mainly due to increased needle tip positioning accuracy. CT guidance provides
      greater anatomical detail that facilitates accurate needle trajectory planning,
      monitoring and final placement. Unlike conventional fluoroscopy that may be
      hindered by tissue overlap and lack of surrounding anatomical detail CT guidance
      offers direct visualization of the entire needle trajectory and the surrounding
      soft tissue and bone structures. Large osteophytes and adjacent vascular
      structures can be identified and safely avoided. The goals of this narrative
      review are to provide a basic overview of CT techniques available for spinal
      interventional pain procedures, to discuss the potential advantages and
      disadvantages of CT guidance, to provide a simple step-by-step approach to use of
      CT guidance, to share technical pearls, and to discuss methods to avoid potential
      pitfalls. This review will provide interventional pain physicians with knowledge
      of relevant CT image acquisition techniques and appropriate radiation dose
      reduction strategies. This will contribute to increased technical success rates
      while reducing radiation dose to the patient and staff. 

PMID- 23877454
TI  - Pain and its interference with daily activities in medical oncology outpatients.
AB  - BACKGROUND: Pain prevalence at various stages of cancer ranges from 27% to 60%
      for outpatients. Yet, how pain is managed in this patient group is poorly
      understood. OBJECTIVES: The primary objective was to assess pain prevalence and
      intensity, and its interference with daily activities, in medical oncology
      outpatients. The secondary objectives were the adequacy of analgesic pain
      treatment and to identify independent predictors for moderate to severe pain.
      STUDY DESIGN: A cross-sectional study. SETTING: Oncology outpatient clinics of 7
      Dutch regional hospitals. METHODS: Four hundred twenty-eight medical oncology
      outpatients were assigned to the study. Pain prevalence and interference of pain
      with daily activities were assessed using the Brief Pain Inventory. Adequacy of
      analgesic treatment was determined by calculating the Pain Management Index
      (PMI). Descriptive statistics, non-parametric tests, and logistic regression
      analysis were conducted. RESULTS: More than one third of all participants
      reported pain (39%). Eighty-three patients (20%) had moderate to severe pain (NRS
      5-10). Analgesic treatment was inadequate in more than half of the patients with
      pain (62%). Interference of pain with daily activities increased with increased
      intensity, yet even 10%-33% of patients suffering mild pain reported high
      interference with daily activities. High current pain intensity and high
      interference with general daily activities predicted moderate to severe pain.
      LIMITATIONS: No characteristics of nonparticipants were available. CONCLUSION:
      Pain remains a significant problem in medical oncology outpatients, and often
      pain is insufficiently managed. Patients with a high pain intensity were more at
      risk to experience pain related interference with daily activities, but even some
      patients suffering mild pain experienced this. As adequate pain relief for up to
      86% of the patients with cancer should be feasible, pain in medical oncology
      outpatients is still undertreated. Taking into account the interference of pain
      with daily activities and predictors of pain will facilitate cancer pain
      management. The study has been approved by the Medical Ethics Committee (CMO) in
      all 7 hospitals (METC protocol number 2011/020) and has been registered by the
      Dutch Trial register (NTR): NTR2739.

PMID- 23877455
TI  - Permanent lesion of the lateral femoral cutaneous nerve after low-volume ethanol
      96%application on the lumbar sympathetic chain.
AB  - Lumbar sympathetic blocks and chemical sympathectomies are used for the pain
      treatment of peripheral arterial occlusive disease or sympathetically maintained
      pain syndrome after nerve injury or complex regional pain syndrome (CRPS). A 30
      year-old patient was referred to the pain department with all the clinical signs
      and symptoms of a CRPS of the right foot one and a half years after being
      surgically treated for rupture of the achilles tendon. An inpatient admission was
      necessary due to insufficient pain reduction upon the current treatment, strong
      allodynia in the medial distal right lower leg and decreased load-bearing
      capacity of the right foot. A computed tomography (CT)-guided lumbar sympathetic
      block at the right L3 (Bupivacaine 0.5%, 4 mL) led to a skin temperature increase
      from 21 degrees  C before block to > 34 degrees  C for about 5 hours after the
      intervention. The patient experienced significant pain relief, indicating
      sympathetically maintained pain. Thus, we performed a CT-guided lumbar
      sympathetic neurolysis at the same level (ethanol 96%, 2 mL) 5 days later,
      achieving again a significant skin temperature increase of the right foot and a
      slight reduction of his pain intensity from numeric rating scale (NRS) 7 prior to
      the intervention to NRS 4 after 8 hours (NRS, 0 = no pain, 10 = strongest pain
      imaginable). Eight months later a repeated inpatient admission was necessary due
      to considerable pain relapse and decreased load-bearing capacity of his right
      foot. A CT-guided lumbar sympathetic neurolysis was repeated at the L4 level on
      the right side and was successful, inducing a significant skin temperature
      increase. Despite a temporary irritation of the genitofemoral nerve 8 hours after
      the intervention, a delayed irritation of the lateral femoral cutaneous nerve
      occurred. This was a long-lasting lesion of the lateral femoral cutaneous nerve
      following a CT-guided chemical sympathectomy with a low-volume ethanol 96%
      application - a complication which has not been described in literature until
      now. This is probably caused by broad dissemination of the neurolytic agent along
      the psoas muscle despite a correct needle position and spread of contrast agent.
      The development of this nerve injury even after injection of a small volume of
      ethanol (2 mL) may be delayed. 

PMID- 23877456
TI  - Intracranial hypotension headache caused by a massive cerebrospinal fluid leak
      successfully treated with a targeted c2 epidural blood patch: a case report.
AB  - Cervical epidural steroid injections, administered either interlaminarly or
      transforaminally, are common injection therapies used in many interventional pain
      management practices to treat cervicalgia or cervicobrachial pain secondary to
      spondylosis or intervertebral disc displacement of the cervical spine. Among the
      risks associated with these procedures are the risk for inadvertent dural
      puncture and the development of positional headache from intracranial
      hypotension. We report the case of a 31-year-old woman with a history of migraine
      and cervicalgia from cervical spine spondylosis and cervical disc degenerative
      disease that developed an intractable orthostatic headache accompanied by nausea
      and vomiting after a therapeutic high cervical intralaminar epidural steroid
      injection was administered directly to the C1-C2 spinal level. Although the
      initial magnetic resonance imaging of the brain was unremarkable, a computed
      tomography myelogram study revealed a massive cerebrospinal fluid (CSF) leak from
      the cervical spine.  Repeated cervical epidural blood patches using a catheter
      targeted to the high cervical spine (C2) to inject 15 mL of autologous blood was
      required to totally alleviate her symptoms after she failed conservative therapy.
      Determining the optimal location or approach to administer an epidural blood
      patch can be a challenge depending on the location of the CSF leak. Our case
      demonstrates that targeted cervical epidural blood patch placement using an
      easily manipulated catheter under fluoroscopic guidance is a safe and effective
      approach to treat a massive CSF leak in the high cervical spine region caused by
      prior therapeutic cervical spine epidural steroid injection. 

PMID- 23877457
TI  - Spinal cord stimulation inhibits cortical somatosensory evoked potentials
      significantly stronger than transcutaneous electrical nerve stimulation.
AB  - BACKGROUND: Despite the good clinical results elicited by spinal cord stimulation
      (SCS), the physiological basis of action of SCS is widely unknown. Inhibition of
      somatosensory evoked potential (SEP) amplitudes by SCS has been described, but it
      is unclear whether this displays dose dependency. Moreover, it is unknown whether
      the pain-relieving effect elicited by SCS correlates with the inhibition of SEPs.
      Finally, this study aimed to answer the question whether there is a difference in
      the effect on SEPs between SCS and transcutaneous electrical nerve stimulation
      (TENS), thus between central nervous system stimulation and peripheral nervous
      system stimulation. METHODS: Ten patients (4 men and 6 women, age range 40-77
      years) with neuropathic lower limb pain were included in the study. All patients
      had implanted SCS systems with percutaneous type electrodes. Cortical SEPs under
      SCS and TENS were measured without stimulation, under stimulation at perception
      threshold (PT), and at maximal threshold (MT) in a crossover design. RESULTS:
      Cortical SEP amplitudes were significantly inhibited by SCS. Stimulation at PT
      and at MT both led to a statistically significant inhibition of the SEP
      amplitude. The difference between amplitude reduction at PT and MT showed a
      tendency towards significance. The degree of SEP amplitude inhibition did not
      correlate with pain relief. Inhibition of SEP amplitudes by TENS was weaker than
      that elicited by SCS. The average percentage of amplitude reduction at MT was
      twice as high under SCS as it was under TENS. No effects on SEP latencies were
      seen. CONCLUSIONS: SCS exerts a significantly stronger inhibition of SEP
      amplitudes than TENS. The data hint at a dose dependency of SCS-induced SEP
      amplitude inhibition. No correlation between SEP amplitude inhibition and pain
      relief was found.

PMID- 23877458
TI  - The effects of randomized controlled trials on vertebroplasty and kyphoplasty: a
      square PEG in a round hole.

PMID- 23877459
TI  - Assessment of the growth of epidural injections in the medicare population from
      2000 to 2011.
AB  - BACKGROUND: Among the many diagnostic and therapeutic interventions available for
      the management of chronic pain, epidural steroid injections are one of the most
      commonly used modalities. The explosive growth of this technique is relevant in
      light of the high cost of health care in the United States and abroad, the
      previous literature assessing the effectiveness of epidural injections has been
      sparse with highly variable outcomes based on technique, outcome measures,
      patient selection, and methodology. However, the recent assessment of
      fluoroscopically directed epidural injections has shown improved evidence with
      proper inclusion criteria, methodology, and outcome measures. The exponential
      growth of epidural injections is illustrated in multiple reports. The present
      report is an update of the analysis of the growth of epidural injections in the
      Medicare population from 2000 to 2011 in the United States. STUDY DESIGN:
      Analysis of utilization patterns of epidural procedures in the Medicare
      population in the United States from 2000 to 2011. OBJECTIVES: The primary
      purpose of this assessment was to evaluate the use of all types of epidural
      injections (i.e., caudal, interlaminar, and transforaminal in the lumbar,
      cervical, and thoracic regions) with an assessment of specialty and regional
      characteristics. METHODS: This assessment was performed utilizing the Centers for
      Medicare and Medicaid Services (CMS) Physician/Supplier Procedure Summary (PSPS)
      Master data from 2000 to 2011. RESULTS: Epidural injections in Medicare
      beneficiaries increased significantly from 2000 to 2011. Overall, epidural
      injections increased 130% per 100,000 Medicare beneficiaries with an annual
      increase of 7.5%. The increases per 100,000 Medicare recipients were 123% for
      cervical/thoracic interlaminar epidural injections; 25% for lumbar/sacral
      interlaminar, or caudal epidural injections; 142% for cervical/thoracic
      transforaminal epidural injections; and 665% for lumbar/sacral transforaminal
      epidural injections. The use of epidurals increased 224% in the radiologic
      specialties (interventional radiology and diagnostic radiology) and 145% in
      psychiatric settings, whereas and physical medicine and rehabilitation
      physicians' use of epidurals increased 520%. LIMITATIONS: Study limitatations
      include lack of inclusion of Medicare Advantage patients. In addition, the
      statewide data is based on claims which may include the contiguous or other
      states. CONCLUSIONS: Epidural injections in Medicare recipients increased
      significantly. The growth was significant for some specialties (radiology,
      physical medicine and rehabilitation, and psychiatry) and for certain procedures
      (lumbosacral transforaminal epidural injections).

PMID- 23877460
TI  - Assessment of the escalating growth of facet joint interventions in the medicare
      population in the United States from 2000 to 2011.
AB  - BACKGROUND: Both the Office of Inspector General (OIG) and reports from studies
      of the utilization of facet joint interventions have expressed that explosive
      increases in facet joint interventions provided to spinal pain patients are a
      major concern. STUDY DESIGN: The study is designed to assess the growth of facet
      joint interventions in managing spinal chronic pain in Medicare beneficiaries
      from 2000 to 2011. OBJECTIVE: To assess the use of facet joint interventions in
      chronic pain management. METHODS: The study was performed utilizing the Centers
      for Medicare and Medicaid Services (CMS) physician supplier procedure summary
      master data from 2000 to 2011. RESULTS: The utilization of all types of facet
      joint interventions increased enormously from 2000 to 2011, with an overall
      increase of 308% per 100,000 Medicare beneficiaries and a 13.6% average annual
      increase. In addition, the highest increases were seen for cervical/thoracic
      radiofrequency neurotomy with 836%, followed by an increase of 662% for
      lumbar/sacral radiofrequency neurotomy, a 359% increase in cervical/thoracic
      facet joint injections, and 228% increase in lumbosacral facet joint injections.
      In reference to the number of procedures performed, however, the highest numbers
      were in the lumbosacral region with 990,449 total procedures of lumbar facet
      joint blocks and 406,378 lumbosacral radiofreqency neurotomies in 2011. Cervical
      and thoracic facet joint nerve blocks were 317,220, whereas cervical and thoracic
      radiofrequency neurotomies were 97,526 in 2011. The data also showed that there
      were enormous increases in the proportion of procedures performed by the
      specialty of physical medicine and rehabilitation, with an increase of 781% and
      an annual increase of 21.9% excluding physicians of physical medicine and
      rehabilitation enrolled as interventional pain management or pain management.
      Even though the numbers were very low for nurse anesthetists, nurse
      practitioners, and physician assistants, the increases were from 143 in 2000 to
      21,263 in 2011, providing an annual increase of 55.2%, an overall increase of
      12,460%. LIMITATIONS: The limitations of this study included a lack of inclusion
      of Medicare participants in Medicare Advantage plans, as well as potential
      documentation, coding, and billing errors. Furthermore, the data provided for
      state utilizations is based on claims data for that state which also may include
      patients from contiguous or other states receiving services in those states.
      CONCLUSIONS: The explosive increase in the number of lumbar facet joint
      interventions performed began to wane in 2008. From 2008 to 2010, the utilization
      of facet joint interventions declined by 6%.

PMID- 23877461
TI  - Utilization and growth patterns of sacroiliac joint injections from 2000 to 2011
      in the medicare population.
AB  - BACKGROUND:   The high prevalence of persistent low back pain and growing number
      of diagnostic and therapeutic modalities employed to manage chronic low back pain
      and the subsequent impact on society and the economy continue to hold sway over
      health care policy. Among the multiple causes responsible for chronic low back
      pain, the contributions of the sacroiliac joint have been a subject of debate
      albeit a paucity of research. At present, there are no definitive conservative,
      interventional or surgical management options for managing sacroiliac joint pain.
      It has been shown that the increases were highest for facet joint interventions
      and sacroiliac joint blocks with an increase of 310% per 100,000 Medicare
      beneficiaries from 2000 to 2011. There has not been a systematic assessment of
      the utilization and growth patterns of sacroiliac joint injections. STUDY DESIGN:
      Analysis of the growth patterns of sacroiliac joint injections in Medicare
      beneficiaries from 2000 to 2011. OBJECTIVES: To evaluate the utilization and
      growth patterns of sacroiliac joint injections. METHODS: This assessment was
      performed utilizing Centers for Medicare and Medicaid Services (CMS)
      Physician/Supplier Procedure Summary (PSPS) Master data from 2000 to 2011.
      RESULTS: The findings of this assessment in Medicare beneficiaries from 2000 to
      2011 showed a 331% increase per 100,000 Medicare beneficiaries with an annual
      increase of 14.2%, compared to an increase in the Medicare population of 23% or
      annual increase of 1.9%. The number of procedures increased from 49,554 in 2000
      to 252,654 in 2011, or a rate of 125 to 539 per 100,000 Medicare beneficiaries.
      Among the various specialists performing sacroiliac joint injections, physicians
      specializing in physical medicine and rehabilitation have shown the most
      increase, followed by neurology with 1,568% and 698%, even though many physicians
      from both specialties have been enrolling in interventional pain management and
      pain management. Even though the numbers were small for nonphysician providers
      including certified registered nurse anesthetists, nurse practitioners, and
      physician assistants, these numbers increased substantially at a rate of 4,526%
      per 100,000 Medicare beneficiaries with 21 procedures performed in 2000
      increasing to 4,953 procedures in 2011. The, majority of sacroiliac joint
      injections were performed in an office setting. The utilization of sacroiliac
      joint injections by state from 2008 to 2010 showed increases of more than 20% in
      New Hampshire, Alabama, Minnesota, Vermont, Oregon, Utah, Massachusetts, Kansas,
      and Maine. Similarly, some states showed significant decreases of 20% or more,
      including Oklahoma, Louisiana, Maryland, Arkansas, New York, and Hawaii. Overall,
      there was a 1% increase per 100,000 Medicare population from 2008 to 2010.
      However, 2011 showed significant increases from 2010. LIMITATIONS: The
      limitations of this study included a lack of inclusion of Medicare participants
      in Medicare Advantage plans, the availability of an identifiable code for only
      sacroiliac joint injections, and the possibility that state claims data may
      include claims from other states. . CONCLUSIONS: This study illustrates the
      explosive growth of sacroiliac joint injections even more than facet joint
      interventions. Furthermore, certain groups of providers showed substantial
      increases. Overall, increases from 2008 to 2010 were nominal with 1%, but some
      states showed over 20% increases whereas some others showed over 20% decreases.

PMID- 23877462
TI  - The use of advanced imaging and representation of workers compensation in
      vertebral augmentation: a single-center comparison with the INVEST Trial.
AB  - BACKGROUND: Vertebral augmentation (VA) techniques have changed the paradigm of
      treatment during the past decade and involve injection of polymethylmethacrylate
      (PMMA) cement directly into a compressed vertebral body. During the summer of
      2009, the INVEST trial was one of 2 randomized controlled studies that reported
      equivalence between vertebroplasty and a control procedure.  OBJECTIVE: In this
      analysis, we sought to compare the subset of patients studied in the INVEST trial
      to a tertiary academic institution with respect to 2 variables: Workers
      compensation status and presence of advanced imaging prior to the procedure.
      STUDY DESIGN: Retrospective review of 634 procedures. METHODS: We performed a
      retrospective review of 634 vertebral augmentation procedures at our institution
      between June 2004 and August 2008, overlapping with the dataset of the INVEST
      trial. The primary comparison was whether patients received Workers compensation
      and/or advanced imaging prior to the procedure. The study was IRB approved, and
      in accordance with HIPAA guidelines. RESULTS: There were 409 patients who
      underwent 634 procedures between June 2004 and August 2008. Among 634 procedures,
      only 3 included Workers compensation. Therefore, the majority of patients (> 99%)
      did not receive Workers compensation compared to the INVEST trial (11 - 13%).
      Similarly, in 629 out of 634 procedures (99.2%), patients underwent advanced
      imaging comprised of magnetic resonance imaging (MRI), computed tomography (CT)
      or bone scan. LIMITATIONS: We simply looked at 2 elements of the patient
      demographic in a time-matched fashion and compared it to the U.S. based INVEST
      trial. It is possible that despite our diligent efforts to review the data set,
      we have inadvertently excluded some patients, the incorporation of whom might
      have changed the statistics. CONCLUSION: We reviewed our time-matched database in
      terms of 2 variables we thought curious in the INVEST trial.  In comparison to
      our practice, where advanced imaging is essentially required and Workers
      compensation largely not seen, these aspects of the INVEST trial's population
      stood out.

PMID- 23877463
TI  - Percutaneous vertebral augmentation assisted by PEEK implant in painful
      osteolytic vertebral metastasis involving the vertebral wall: experience on 40
      patients.
AB  - BACKGROUND: Vertebral metastases are associated with significant pain,
      disability, and morbidity. Open surgery for fracture stabilization is often
      inappropriate in this cancer population due to a poor risk-benefit profile,
      particularly if life expectancy is short. Vertebroplasty and kyphoplasty are
      appealing adjunctive procedures in patients with malignancy for alleviation of
      intractable pain. However, these patients have a higher risk of serious
      complications, notably cement extravasation. STUDY DESIGN: We prospectively
      evaluated clinical results of polyetheretherketone (PEEK) implant (Kiva) assisted
      vertebroplasty performed in malignant painful osteolytic lesions at risk for
      cement extravasation due to vertebral wall involvement. SETTING: Department of
      Interventional Radiology, Institute for Cancer Research and Treatment, Candiolo,
      Turin, Italy METHODS: Forty patients (22 women; mean age 66.8 +/- 12.4),
      suffering from a painful spine malignancy with vertebral wall involvement not
      responding to conventional therapies and without surgical indications, underwent
      vertebral augmentation with Kiva intravertebral implant for pain palliation. The
      procedure was performed with moderate sedation and local anesthesia under
      combined digital fluoroscopy and computed tomography guidance. After the coil
      shaped PEEK implant was deployed within the vertebral lesion, bone cement was
      injected under continuous digital fluoroscopic control. Patients were discharged
      from the hospital the next procedural day. The Visual Analog Scale (VAS) for
      pain, Oswestry Disability Index (ODI), analgesic requirement, and use of external
      brace support were evaluated to determine efficacy. The primary end-point was
      safety and efficacy at one month after the procedure. However, all the patients
      were scheduled to be followed-up at month 3, 6, and every 6 months thereafter.
      Follow-up was prospectively evaluated in all patients after Kiva with clinical
      interviews. The Institution's Internal Review Board approved this study. RESULTS:
      Median pre-treatment VAS of 10 (range 6 - 10) significantly (P < 0.001) dropped
      to one (range 0 - 3), with all patients achieving a clinically relevant benefit
      on pain at one month. Differences in pre- and post-treatment analgesic therapy
      were significant (P < 0.001). All patients no longer use an external brace after
      Kiva. In 7 out of 43 (16.3%) treated vertebrae a bone cement leakage was
      detected. LIMITATIONS: This is a not randomized study. Participants were limited
      to 40 patients. CONCLUSION: The Kiva System potentially represents a novel and
      effective minimally invasive treatment option for patients suffering from severe
      pain due to osteolytic vertebral metastases.

PMID- 23877464
TI  - Vertebroplasty for the compression of the dorsal root ganglion due to spinal
      metastasis.
AB  - BACKGROUND: Radicular pain has been considered to be a relative contraindication
      to vertebroplasty. It was reported by some authors in the literature that
      percutaneous vertebroplasty (PV) in these conditions were performed without
      complications. OBJECTIVE: We describe a patient with radicular pain related to
      compression of the dorsal root ganglion by malignant tumor which was relieved
      after PV. STUDY DESIGN: Case report. SETTING: Pain management clinic. CASE
      REPORT:  A 52-year-old man with spine metastasis involving the dorsal root
      ganglion of the left L4 nerve was admitted to the pain clinic with a tingling
      sensation and pain in both legs for 6 months. He was not able to lie on his back
      with his left leg extended or stand without weakness. The transforaminal epidural
      block had only a transient effect. The patient planned to undergo PV. He
      complained of severe radicular pain in his left leg approximately 5 minutes after
      the vertebroplasty. A left L4/5 transforaminal epidural block was performed. The
      next day, the patient's pain was relieved without any complications. He underwent
      palliative radiation therapy for multiple metastases of the thoracolumbar spine.
      At 5 months follow-up, he could lie on his back without recurrence of radicular
      pain. LIMITATIONS: This report describes a single case report. CONCLUSION: We
      suggest that carefully performed PV is an option for terminally ill patients with
      epidural and dorsal root ganglion involvement who do not respond to conservative
      treatment or cannot undergo radiation therapy and surgery. PV is minimally
      invasive compared to open surgery and may merit serious consideration in patients
      with limited physiologic reserves.

PMID- 23877465
TI  - Clinical measurement of intravertebral pressure during vertebroplasty and
      kyphoplasty.
AB  - BACKGROUND: Vertebroplasty (VP) and kyphoplasty (KP) are emerging procedures for
      almost immediate pain relief when treating osteoporotic or osteolytic fractures.
      The main reported complication is polymethylmethacrylate (PMMA) leakage, which
      may lead to compression of neural structures or embolism. Different authors have
      proposed that intravertebral pressure (IP) is an important factor determining the
      risk for leakage, although so far only limited information has been gathered from
      clinical and experimental studies. There is also a lack of understanding of the
      IP during conventional interventions in VP and KP in the clinic. OBJECTIVE: (1)
      To compare the intravertebral pressures of compressed vertebrae and adjacent
      normal vertebrae. (2) To measure the IP of compressed vertebrae during VP and KP.
      SETTING: An interventional pain management practice, a medical center, major
      metropolitan city, in the People's Republic of China. METHODS: Thirty-five
      patients (with 40 compressed vertebrae and 35 adjacent normal vertebrae) were
      randomly allocated for intravertebral pressure measurements. Cannulas were placed
      bipedicularly into the posterior third of each vertebral body. Either PMMA or a
      balloon was injected into the vertebral body through the right cannula. A
      manometer was connected to the cannula in the left pedicle, and heparin was
      injected to verify the pressure measurement system. RESULTS: The range (minimum
      maximum), average IP, and the standard deviation of the compressed vertebrae were
      0-39 mm Hg and 24.5 +/-11.3 mm Hg; and that of adjacent normal vertebrae were 3
      16 mm Hg, 7.3 +/- 4.2 mm Hg. Furthermore, the average IP for Phase 1 (before PMMA
      injection) for VP was 23 +/-11.9 mm Hg; the maximum IP recorded during injection
      was 169 +/- 46.8 mm Hg and the IP for 10 minutes after injection was 33 +/-9.4 mm
      Hg. Meanwhile, the highest IP recorded for KP patients was 142 +/-39.6 mm Hg. The
      average IP for Phase 1 (before balloon inflation) was 24 +/-12.7 mmHg; Phase 2
      (peak IP during the balloon inflation) was 63 +/- 25.8 mm Hg; and Phase 3 (after
      balloon inflation/before PMMA injection) was , and 18 +/- 10.8 mm Hg. The IP for
      10 minutes after injection in KP patients was 36 +/- 8.5 mm Hg. LIMITATIONS: The
      flow rate was manually controlled, which is in line with clinical routine, and
      was kept at approximately 0.1 mL/s. Because the speed of injection was controlled
      by hand, an exact injection rate could not be assured, leading to some inaccuracy
      when comparing the IP of VP and KP patients. Each patient was injected with a
      different PMMA volume. Because PMMA injection was performed to a satisfactory
      vertebral body filling and limited by any signs of extravasation, it was
      difficult to maintain a constant injection volume, unlike in vitro studies. Other
      factors such as the damage to the vertebral shell or the degree of osteoporosis
      might also have affected the intravertebral pressure. CONCLUSION: This study
      showed that the IP of compressed vertebrae was significantly higher than that of
      adjacent normal vertebrae. There was a significant increase in IP during the PMMA
      filling in VP and KP; the IP of compressed vertebrae was not significantly
      reduced by the balloon inflation in KP, and no statistically significant
      differences in IP were found during all common stages of PMMA filling in VP and
      KP.

PMID- 23877466
TI  - Symptomatic cervical vertebral hemangioma treated by percutaneous vertebroplasty.
AB  - BACKGROUND: Vertebral hemangioma (VH) is considered to be a benign lesion of bone
      with a rich vasculature. Most incidentally discovered hemangiomas are
      asymptomatic. Percutaneous vertebroplasty (PVP) has demonstrated efficacy in the
      treatment of symptomatic thoracic and lumbar VHs. To our knowledge, the reports
      concerning PVP on symptomatic cervical VHs are quite rare. OBJECTIVE: Our intent
      was to assess PVP as treatment for symptomatic cervical hemangiomas. STUDY
      DESIGN: Prospective evaluation. SETTING: An inteventional pain management
      practice, single medical center. METHODS: Eight patients with symptomatic
      cervical VHs were enrolled between December 2008 and February 2012, all of whom
      underwent magnetic resonance imaging (MRI) of the cervical spine. The patients
      with 8 vertebral bodies of VHs were treated by using PVP. The clinical and
      radiological data were collected and analyzed. Postoperative outcomes were
      determined using a visual analog scale. RESULTS: Surgical levels include C3 (2
      patients), C4 (3 patients), C5 (2 patients), and C6 (one patient). The average
      follow-up period was 27.4 months, with a minimum of 12 months. Mean operative
      time and x-ray exposure time were respectively 35 +/- 7.1 minutes and 25 +/- 7.7
      seconds. The visual analogue scale for neck pain decreased significantly from 6.9
      +/- 0.6 preoperatively to 1.3 +/- 0.5 (P < 0.01) on the second day after surgery,
      with a final score of 1.2 +/- 0.5 (P < 0.01). Cement distribution was always
      diffuse and homogeneous. No cement leakage was observed in all cases except for 2
      patients. There were no other major complications at the time of last follow-up
      evaluation. LIMITATIONS: An observational clinical trial with a relatively small
      sample size. CONCLUSION: Short-term results indicate that PVP appears to be an
      effective and safe treatment for symptomatic cervical VHs.

PMID- 23877467
TI  - Vertebroplasty for treatment of osteolytic metastases at C2 using an
      anterolateral approach.
AB  - BACKGROUND: The clinical management of osteolytic metastases involving C2 is
      unique, because it is challenging to approach these lesions. Symptoms may vary
      from local pain to progressive neurological deficit. Surgery or radiotherapy have
      been the treatments of choice for several years; however, surgery may not bean
      option for patients with multiple metastases and poor general medical status, and
      radiotherapy carries the risk of vertebral collapse and consequent neural
      compression due to delayed bone reconstruction. Through different approaches,
      vertebroplasty has been introduced into clinical practice as an alternative to
      traditional surgical and radiotherapy treatments of osteolytic metastases at C2.
      OBJECTIVE: This study aimed to evaluate the safety and efficacy of vertebroplasty
      with an anterolateral approach for osteolytic metastases at C2 under fluoroscopic
      guidance. STUDY DESIGN: Vertebroplasty in 13 patients with osteolytic metastases
      at C2 and its clinical effects were evaluated. SETTING: This study was conducted
      in an interventional therapy group at a medical center in a major Chinese city.
      METHODS: Thirteen consecutive patients were treated with vertebroplasty via an
      anterolateral approach. The researchers followed up with the patients for 3 to 12
      months, with an average of 9.2 months. The clinical effects were evaluated with
      the visual analog scale (VAS) pre-operatively and at 3 days, one month, 3 months,
      6 months, and 12 months post-operatively. RESULTS: Thirteen consecutive patients
      were successfully treated with a satisfying resolution of painful symptoms.
      Extraosseous cement leakages were found in 5 cases without any clinical
      complications. VAS scores decreased from 7.6 +/- 0.9 pre-operatively to 2.1 +/-
      1.9 by the 3-day post-operative time point, and were 1.8 +/- 1.7 at one month,
      1.7 +/- 1.8 at 3 months, 0.9 +/- 0.8 at 6 months, and 0.6 +/- 0.5 at 12 months
      after the procedure. There was a significant difference between the mean pre
      operative baseline score and the mean score at all of the post-operative follow
      up points (P < 0.001). LIMITATIONS: This was an observational study with a
      relatively small sample size. CONCLUSIONS: Vertebroplasty via an anterolateral
      approach is an effective technique to treat osteolytic metastases involving C2.
      It is a valuable, minimally invasive, and efficient method that allows quick and
      lasting resolution of painful symptoms.

PMID- 23877468
TI  - Intradiscal pulsed radiofrequency for chronic lumbar discogenic low back pain: a
      one year prospective outcome study using discoblock for diagnosis.
AB  - BACKGROUND: Discogenic pain is an important cause of low back pain (LBP). We have
      developed a pulsed radiofrequency (PRF) technique, using Diskit II needles
      (NeuroTherm, Middleton, MA, USA) placed centrally in the disk, for applying
      radiofrequency current in the disc (Intradiscal PRF method). OBJECTIVE: The
      purpose of this study was to investigate the effect of this intradiscal pulsed
      radiofrequency method in patients with chronic discogenic LBP diagnosed by
      discoblock, in terms of pain relief and reduction of disability. STUDY DESIGN:
      Prospective case series clinical outcome study. METHODS: The participants
      consisted of 23 patients with a mean age of 35.3 +/- 9.86 years with chronic
      discogenic LBP that was not responsive to aggressive nonoperative care. A Diskit
      II needle (15-cm length, 20G needle with a 20-mm active tip) was placed centrally
      in the disc. PRF was applied for 15 minutes at a setting 5x5 ms/s and 60 V.
      Outcome measures included the pain intensity score on a 0-10 numeric rating scale
      (NRS) and the Roland-Morris Disability Questionnaire (RMDQ) at pre-treatment,
      one, 3, 6, and 12 months post-treatment. RESULTS: The mean pain severity scores
      (NRS) improved significantly from 7.47 +/- 0.85 pre-treatment to 3.13 +/- 2.58 at
      the 12 month follow-up (P < 0.01). The RMDQ showed significant (P < 0.01)
      improvement from 11.4 +/- 1.57 pre-treatment to 2.90 +/- 2.97 at the 12 month
      follow-up (P < 0.01). Nineteen of 23 (82.6%) of the patients demonstrated NRS
      improvements of greater than 2, and 15 of 23 (65.2%) had > 50% pain reduction, 12
      months after treatment. LIMITATIONS: The number of patients was relatively low
      and secondary outcomes such as medication requirement or psychological effects
      were not addressed. CONCLUSIONS: This intradiscal PRF method with consecutive PRF
      5/5/60V, 15 min (with Diskit needle) appears to be a safe, minimally invasive
      treatment option for patients with chronic discogenic LBP.

PMID- 23877469
TI  - Pulsed radiofrequency for chronic abdominal pain.

PMID- 23877470
TI  - Neuromuscular ultrasound in carpal tunnel syndrome: a tool for cutting a gordian
      knot.

PMID- 23877471
TI  - Preoperative ultrasound of the MN-UA may help to identify patients at risk for
      iatrogenic lesion: in response.

PMID- 23877472
TI  - The role of interleukin 10 in the associations between migraine and Helicobacter
      pylori infection.

PMID- 23877476
TI  - Jim Morrison, Friend and Colleague.
AB  - Our long-time association with Jim Morrison and the work that came from it is the
      result of a series of fortunate coincidences. We are pleased to be able to share
      recollections here of our interactions with Jim and how his life and work have
      influenced us and the field of mass spectrometry. 

PMID- 23877475
TI  - Osteoporosis and cancer.
AB  - Cancer is a major risk factor for bone loss and fractures. This is due both to
      direct effects of cancer cells on the skeleton and to deleterious effects of
      cancer-specific therapies on bone cells. Marked improvements in survival for many
      cancers mean that strategies to limit bone loss and reduce fracture risk must be
      incorporated into the care plans for nearly all patients with cancer. The vast
      majority of effort thus far has focused on bone loss in patients with breast and
      prostate cancers, with comparatively few studies in other malignancies.
      Antiresorptive therapies have proven nearly universally effective for limiting
      bone loss in cancer patients, although few studies have been powered sufficiently
      to include fractures as primary endpoints, and patients are frequently neither
      identified nor treated according to published guidelines. Nonpharmacologic
      approaches to limit falls, particularly in elderly patients, are also likely
      important adjunctive measures for most cancer patients.

PMID- 23877477
TI  - Deep sedation without intubation for ERCP is appropriate in healthier, non-obese
      patients.
AB  - BACKGROUND: Providing the appropriate anesthesia for endoscopic retrograde
      cholangiopancreatography (ERCP) cases is challenging. AIM: The aim of our study
      was to prospectively assess the safety of anesthesia directed deep sedation
      (ADDS) in non-intubated patients compared to general endotracheal anesthesia
      (GET) during an ERCP. METHODS: We conducted a prospective observational study in
      patients undergoing an ERCP. The choice of anesthetic-ADDS or GET-was made by the
      anesthesiologist. The pre-anesthesia assessment, intraoperative vital signs, and
      medications administered were collected. A standardized study instrument was used
      to record the number of procedure interruptions, intraprocedure and recovery room
      adverse events (AE). RESULTS: A total of 393 (89.7 %) patients received ADDS (no
      intubation) and 45 (10.2 %) received a GET. Age and comorbidities were similar in
      ADDS and GET groups. BMI was higher in the GET (32.6 +/- 9.5) versus in the ADDS
      (27.3 +/- 6.1) group; p < 0.001. The number of ASA 2 patients was higher in the
      ADDS versus the GET group (38.7 versus 22.2 %; p < 0.04); the number of ASA 4
      patients was 15.6 % of GET versus 6.6 % of the ADDS cases (p = 0.05). During the
      procedure 16 (3.7 %) ADDS patients were intubated and converted to a GET
      anesthetic; 4 (25 %) of the converted ADDS cases were ASA 4 versus 6.4 % of ADDS
      patients (p = 0.006). Intraprocedure events occurred in 35.6 % of GET and 25.7 %
      of ADDS cases, without significant complications. CONCLUSION: Our data suggest
      that the administration of anesthesia without intubation for prone ERCP cases is
      feasible especially in non-obese, healthier patients.

PMID- 23877478
TI  - Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.
AB  - Noonan syndrome is a common autosomal dominant neurodevelopmental disorder caused
      by gain-of-function germline mutations affecting components of the Ras-MAPK
      pathway. The authors present the case of a 6-year-old male with Noonan syndrome,
      Chiari malformation type I, shunted benign external hydrocephalus in infancy, and
      unique cerebrovascular changes. A de novo heterozygous change in the RAF1 gene
      was identified. The patient underwent brain magnetic resonance imaging, computed
      tomography angiography, and magnetic resonance angiography to further clarify the
      nature of his abnormal brain vasculature. The authors compared his findings to
      the few cases of Noonan syndrome reported with cerebrovascular pathology. 

PMID- 23877479
TI  - A novel c.1135_1138delCTGT mutation in CLN3 leads to juvenile neuronal ceroid
      lipofuscinosis.
AB  - Neuronal ceroid lipofuscinosis is the most common childhood neurodegenerative
      disorder in the world, with an incidence of 1 in 100,000 live births. More than
      400 mutations in at least 14 different genes are linked to multiple clinical
      variants. These progressive genetic disorders primarily manifest in the central
      nervous system due to an extensive loss of neurons, primarily in the cerebral and
      cerebellar cortices. Juvenile neuronal ceroid lipofuscinosis is the most common
      form and is primarily due to mutations in CLN3, which encodes a protein of
      unknown function. The most common such mutation in CLN3 is a 1.02-kb deletion
      that results in a frameshift and subsequent premature termination codon. Here we
      describe a patient with juvenile neuronal ceroid lipofuscinosis who has a novel
      c.1135_1138delCTGT mutation in CLN3. This deletion induces a frameshift and
      premature termination codon in CLN3 messenger ribonucleic acid that is likely
      recognized by nonsense-mediated decay and degraded, subsequently leading to
      decreased CLN3 protein abundance.

PMID- 23877480
TI  - Executive function and cerebrovascular reactivity in pediatric hypertension.
AB  - Primary hypertension is associated with decreased performance on neurocognitive
      testing and a blunted cerebrovascular reactivity to hypercapnia. Parents of 14
      children with hypertension and prehypertension completed the Behavior Rating
      Inventory of Executive Functions. Children underwent 24-hour ambulatory blood
      pressure monitoring and transcranial Doppler with reactivity measurement using
      time-averaged maximum mean velocity and end-tidal carbon dioxide during
      hypercapnia-rebreathing test. Comparing the reactivity slope for the patients to
      historical controls showed a statistically significant difference (t = -5.19, df
      = 13, P < .001), with lower slopes. Pearson correlations of the Behavior Rating
      Inventory of Executive Functions scores with the reactivity slopes showed a
      statistically significant inverse relationship with Behavioral Regulation Index
      (r = -.60, P = .02), Metacognition Index (r = -.40, P = .05), and the Global
      Executive Component (r = -.53, P = .05). Children with hypertension have
      decreased executive function, and this correlates to low transcranial Doppler
      reactivity slopes, suggesting that the brain is a target organ in hypertensive
      children.

PMID- 23877481
TI  - Rationale for the design of an oncology trial using a generic targeted therapy
      multi-drug regimen for NSCLC patients without treatment options (Review).
AB  - Despite more than 70 years of research concerning medication for cancer
      treatment, the disease still remains one of the leading causes of mortality
      worldwide. Many cancer types lead to death within a period of months to years.
      The original class of chemotherapeutics is not selective for tumor cells and
      often has limited efficacy, while treated patients suffer from adverse side
      effects. To date, the concept of tumor-specific targeted therapy drugs has not
      fulfilled its expectation to provide a key for a cure. Today, many oncology
      trials are designed using a combination of chemotherapeutics with targeted
      therapy drugs. However, these approaches have limited outcomes in most cancer
      indications. This perspective review provides a rationale to combine targeted
      therapy drugs for cancer treatment based on observations of evolutionary
      principles of tumor development and HIV infections. In both diseases, the
      mechanisms of immune evasion and drug resistance can be compared to some extent.
      However, only for HIV is a breakthrough treatment available, which is the highly
      active antiretroviral therapy (HAART). The principles of HAART and recent
      findings from cancer research were employed to construct a hypothetical model for
      cancer treatment with a multi-drug regimen of targeted therapy drugs. As an
      example of this hypothesis, it is proposed to combine already marketed targeted
      therapy drugs against VEGFRs, EGFR, CXCR4 and COX2 in an oncology trial for non
      small cell lung cancer patients without further treatment options.

PMID- 23877483
TI  - Appropriate use criteria in echocardiography: is no change the same as no
      benefit?

PMID- 23877482
TI  - Exploring the genome of the salt-marsh Spartina maritima (Poaceae, Chloridoideae)
      through BAC end sequence analysis.
AB  - Spartina species play an important ecological role on salt marshes. Spartina
      maritima is an Old-World species distributed along the European and North-African
      Atlantic coasts. This hexaploid species (2n = 6x = 60, 2C = 3,700 Mb) hybridized
      with different Spartina species introduced from the American coasts, which
      resulted in the formation of new invasive hybrids and allopolyploids. Thus, S.
      maritima raises evolutionary and ecological interests. However, genomic
      information is dramatically lacking in this genus. In an effort to develop
      genomic resources, we analysed 40,641 high-quality bacterial artificial
      chromosome-end sequences (BESs), representing 26.7 Mb of the S. maritima genome.
      BESs were searched for sequence homology against known databases. A fraction of
      16.91% of the BESs represents known repeats including a majority of long terminal
      repeat (LTR) retrotransposons (13.67%). Non-LTR retrotransposons represent 0.75%,
      DNA transposons 0.99%, whereas small RNA, simple repeats and low-complexity
      sequences account for 1.38% of the analysed BESs. In addition, 4,285 simple
      sequence repeats were detected. Using the coding sequence database of Sorghum
      bicolor, 6,809 BESs found homology accounting for 17.1% of all BESs. Comparative
      genomics with related genera reveals that the microsynteny is better conserved
      with S. bicolor compared to other sequenced Poaceae, where 37.6% of the paired
      matching BESs are correctly orientated on the chromosomes. We did not observe
      large macrosyntenic rearrangements using the mapping strategy employed. However,
      some regions appeared to have experienced rearrangements when comparing Spartina
      to Sorghum and to Oryza. This work represents the first overview of S. maritima
      genome regarding the respective coding and repetitive components. The syntenic
      relationships with other grass genomes examined here help clarifying evolution in
      Poaceae, S. maritima being a part of the poorly-known Chloridoideae sub-family.

PMID- 23877484
TI  - Influence of individual energy cost on running capacity in warm, humid
      environments.
AB  - PURPOSE: Challenging environmental conditions including heat and humidity are
      associated with particular risks to the health of runners and triathletes during
      prolonged events. The heat production of a runner is the product of its energy
      cost of running (C r) by its velocity. Since C r varies greatly among humans,
      those individuals with high C r are more exposed to heat stress in warm and humid
      conditions. Although risk factor awareness is crucial to the prevention of heat
      stroke and potential fatalities associated therewith, how C r affects the highest
      sustainable velocity (V) at which maximal heat loss matches heat production has
      not been quantified to date. METHODS: Here, we computed in virtual runners
      weighting 45-75 kg, the influence of C r variability from 3.8 to 4.4 J.m(-1).kg(
      1) on V. Heat loss by radiation, convection, and conduction was assessed from
      known equations including body dimensions, running velocity (3.4-6.2 m.s(-1)),
      air temperature (T a, 10-35  degrees C) and relative humidity (r h, 50, 70 and 90
      %). RESULTS: We demonstrated a marked and almost linear influence of C r on V in
      hot and humid conditions: +0.1 J.kg(-1).m(-1) in C r corresponded to -4 % in V.
      For instance, in conditions 25  degrees C r h 70 %, 65-kg runners with low C r
      could sustain a running speed of 5.7 m.s(-1) as compared to only 4.3 m.s(-1) in
      runners with high C r, which is huge. CONCLUSION: We conclude that prior
      knowledge of individual C r in athletes exposed to somewhat warm and humid
      environments during prolonged running is one obvious recommendation for
      minimizing heat illness risk.

PMID- 23877485
TI  - The great mimicker: IgG4-related disease.
AB  - IgG4-related disease is defined as a multi-organ systemic disorder with
      pathological findings affecting a wide range of organ systems. The condition
      unifies a large number of clinical diagnoses previously considered as being
      confined to single organ systems. At present, several issues related to its
      pathophysiology remained controversial, including the natural history of the
      disease, the pathogenic role of IgG4, and its use as a biomarker. Glucocorticoids
      are considered the treatment of choice for remission induction of IgG4-related
      disease manifestations; however, concerns regarding duration of therapy and
      management of refractory disease remained to be elucidated. 

PMID- 23877486
TI  - The effectiveness of tofacitinib, a novel Janus kinase inhibitor, in the
      treatment of rheumatoid arthritis: a systematic review and meta-analysis.
AB  - The aim of the present study was to conduct a meta-analysis of the effectiveness
      of tofacitinib, a novel oral Janus kinase inhibitor, recently approved for the
      treatment of active rheumatoid arthritis in patients who have failed previous
      treatment with methotrexate (MTX) or other disease-modifying antirheumatic drugs
      (DMARDs). A systematic literature search was conducted in PubMed, EMBASE,
      Cochrane Library, and other databases till 3 May 2013. All included studies were
      analyzed with the use of the Review Manager 5.1.0. software according to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      Statement protocol. Nine randomized controlled trials (RCTs) comparing
      tofacitinib with placebo were identified. Two of them additionally provided the
      comparison with adalimumab. However, only eight RCTs met the inclusion criteria
      for the meta-analysis. The overall results of the meta-analysis showed that
      tofacitinib provided a statistically significant improvement according to the
      response criteria (ACR20/50/70) after 12 weeks of treatment when compared to
      placebo (p < 0.00001). Moreover, it was demonstrated that tofacitinib was
      significantly superior to adalimumab in achieving the ACR50 response criteria at
      week 12 (p = 0.003). For the safety analysis, there were no statistically
      significant differences between tofacitinib-, adalimumab-, and placebo-treated
      patients in respect to the risk of serious adverse events or treatment
      discontinuation due to adverse reactions (p > 0.05). The findings of this
      systematic review with meta-analysis indicate that tofacitinib monotherapy or
      with background methotrexate provides early statistically significant and
      clinically important improvement in rheumatoid arthritis symptoms and has an
      acceptable safety profile comparable to that of placebo. The results of the
      present meta-analysis show that the frequency of serious adverse events was not
      increased after tofacitinib treatment. In addition, tofacitinib might provide an
      effective treatment option compared to intravenous or subcutaneous biological
      DMARDs, as suggested by the result of the comparison made regarding tofacitinib
      vs. adalimumab ACR50 response rate.

PMID- 23877487
TI  - Cost per responder of TNF-alpha therapies in Germany.
AB  - Tumor necrosis factor alpha (TNF-alpha) inhibitors ranked highest in German
      pharmaceutical expenditure in 2011. Their most important application is the
      treatment of rheumatoid arthritis (RA). Our objective is to analyze cost per
      responder of TNF-alpha inhibitors for RA from the German Statutory Health
      Insurance funds' perspective. We aim to conduct the analysis based on randomized
      comparative effectiveness studies of the relevant treatments for the German
      setting. For inclusion of effectiveness studies, we require results in terms of
      response rates as defined by European League Against Rheumatism (EULAR) or
      American College of Rheumatology (ACR) criteria. We identify conventional triple
      therapy as the relevant comparator. We calculate cost per responder based on
      German direct medical costs. Direct clinical comparisons could be identified for
      both etanercept and infliximab compared to triple therapy. For infliximab, cost
      per responder was 216,392 euros for ACR50 and 432,784 euros for ACR70 responses.
      For etanercept, cost per ACR70 responder was 321,527 euros. Cost was lower for
      response defined by EULAR criteria, but data was only available for infliximab.
      Cost per responder is overestimated by 40% due to inclusion of taxes and
      mandatory rebates in German drugs' list prices. Our analysis shows specific
      requirements for cost-effectiveness analysis in Germany. Cost per responder for
      TNF-alpha treatment in the German setting is more than double the cost estimated
      in a similar analysis for the USA, which measured against placebo. The difference
      in results shows the critical role of the correct comparator for a specific
      setting.

PMID- 23877488
TI  - Profile of inflammatory mediators in tonsils of patients with periodic fever,
      aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.
AB  - The purpose of this study was to analyze the levels of white blood cells and
      profile of proinflammatory Th1, Th2, Th17, and T regulatory tissue cytokines in
      the tonsils of periodic fever, aphthous stomatitis, pharyngitis, and cervical
      adenitis (PFAPA) patients to contribute to the pathophysiological understanding
      of the PFAPA syndrome. A cohort of PFAPA patients who had tonsillectomy during
      2010 and 2011 was included and compared to control patients who had tonsillectomy
      for tonsillar hypertrophy. White blood cell counts were measured during flares in
      PFAPA patients and before tonsillectomy in the control group. Cytokine gene
      expression was analyzed in removed tonsils by real-time PCR. Nine PFAPA patients
      with a median age of 5.3 years (1.7-8 years) and 17 hypertrophic tonsils of
      patients with a median age of 4.8 years (2.3-8.4 years) participated in this
      study. Tonsillectomy was performed during afebrile period between PFAPA flares.
      Three of the nine patients had recurrent episodes of aphthous stomatitis without
      fever after tonsillectomy. Leukocyte and neutrophil counts were higher in PFAPA
      patients compared to controls (p < 0.05). Eosinophil counts were lower in PFAPA
      patients during flares (p = 0.006). IL-1beta, TNF-alpha, TGF-beta, IL-17, and IFN
      gamma levels were similar in the tonsils of patients and controls. IL-4 gene
      expression in the tonsils was lower in PFAPA patients compared to those of the
      controls (p = 0.04). Proinflammatory, effector, and regulatory cytokine gene
      expression in tonsil tissue of PFAPA children removed in a noninflammatory
      asymptomatic interval and in control patients were similar. However, IL-4
      cytokine gene expression in the tonsils and peripheral blood eosinophils were
      lower in the PFAPA patients suggesting a potential pathogenesis pathway based on
      an inhibition of Th2 responses.

PMID- 23877489
TI  - Interleukin-27 as a potential therapeutic target for rheumatoid arthritis: has
      the time come?
AB  - Interleukin (IL)-27 is a novel member of the IL-6/IL-12 family of cytokines with
      a broad range of pro- and anti-inflammatory properties. Recently, accumulating
      evidence has shown that IL-27 can play either a pathogenic or a protective role
      in animal models of inflammatory arthritis, depending upon the model and
      underlying pathogenic mechanisms. As to human system, elevated expression of IL
      27 has clearly been detected in the synovial membranes and fluid from patients
      with rheumatoid arthritis (RA). Moreover, stimulation of IL-27 receptor with IL
      27 of fibroblast-like synoviocytes from RA had a suppressive effect on the
      production of proinflammatory cytokines in vitro. All these findings suggest that
      IL-27 may have promise as a potential therapeutic target for RA. In this review,
      we will discuss the biological features of IL-27 and summarize recent advances on
      both pathogenic and protective roles of IL-27 in RA. 

PMID- 23877491
TI  - Acceptance of human papillomavirus (HPV) vaccination among young women in a
      country with a high prevalence of HPV infection.
AB  - Cervical cancer is the second most common cancer among women in Argentina and the
      mortality has remained unchanged for the last 30 years. The 2011 national
      implementation of human papillomavirus (HPV) vaccination will be a key component
      of future cervical cancer prevention. Vaccination of young adult women is not
      included in the program, although these women could also benefit from the
      vaccine, especially in underserved areas with a high prevalence of HPV. However,
      research on acceptance of HPV vaccination within this group is scarce. The aim of
      this study was to investigate acceptance of HPV vaccination, the correlation
      between acceptance and cost, as well as other factors and perceptions of HPV
      vaccination among young adult women in Argentina. In total, 174 young women aged
      18-30 years were included in this quantitative cross-sectional hospital-based
      study in a low resource area of the Mendoza Province, conducted through
      structured questionnaire-based interviews. Multinomial logistic regression models
      were used to investigate correlates of acceptance. Acceptance of HPV vaccination
      was high if it was free (95%) and even if it was not (75%). A significant
      positive association was found between acceptance and belief in vaccine safety
      (p=0.01) and between acceptance and not being a welfare recipient (p=0.00).
      Nearly half the participants incorrectly believed that they would be fully
      protected against cervical cancer after vaccination. Our findings suggest that
      acceptance of HPV vaccination is high among young women in a high-risk,
      relatively underserved area, even if vaccination is not free. Extensive
      misconceptions about the vaccine, however, highlight the need for further
      education about HPV vaccination.

PMID- 23877490
TI  - Eligibility criteria in knee osteoarthritis clinical trials: systematic review.
AB  - There is an increasing concern over generalizability of trial results. We
      investigated eligibility criteria of knee osteoarthritis clinical trials.
      Eligible trials were randomized, placebo-controlled trials that were identified
      by searches in MEDLINE, SCOPUS, and the Cochrane Central Register of Controlled
      Trials. We then attempted to extract data on the eligibility criteria by
      employing predetermined criteria. From 355 randomized knee osteoarthritis trials,
      we reviewed data categorized by non-osteoarthritis-related and osteoarthritis
      related factors. A variety of items were used in the eligibility criteria.
      Regarding the non-osteoarthritis-related factors, ethical considerations, such as
      inability to give an informed consent (79.4 %) or medical conditions potential
      for risks by test treatments (56.0 %) or by participation in a trial (57.2 %),
      were the common reasons for excluding patients from a trial. Concerning the
      osteoarthritis-related factors, most of the trials did not specify age and
      symptom severity. When trials specifying these items were investigated, patients
      with 40 to 80 years in age and grade 2 in the Kellgren-Lawrence scale were mostly
      included into a trial. For the pain intensity, patients with >=20-40 in the 100
      mm visual analog scale and >=6-8 in the WOMAC pain subscale were commonly
      enrolled into a trial. These findings warrant further investigation on the
      generalizability of trial results.

PMID- 23877492
TI  - [Causes and causation: notes of epidemiology for research and daily activity].

PMID- 23877493
TI  - [Assessment of non-traumatic chest pain in emergency room: comparison between
      heart score and triage assessment of an Italian hospital].
AB  - INTRODUCTION: Triage for non-traumatic chest pain is a difficult issue for nurses
      in Emergency Department. AIM: To compare sensibility and specificity of usual
      triage and HEART score. METHODS: A retrospective cohort study was conducted in
      the Emergency Room of Citta della Salute e della Scienza - Molinette Hospital of
      Turin (Italy). Data about triage of patients with non-traumatic chest pain were
      retrieved and HEART score was calculated by a nurse blind to the triage
      assessment. RESULTS: Data on 428 patients were collected. The assessment with the
      HEART score showed a significantly higher sensitivity and specificity, respect to
      usual triage (p-value for comparison: 0.01 and 0.0001, respectively). Moreover
      the HEART score better identified patients with delayed risk. CONCLUSIONS: HEART
      score can be considered a more effective tool for the assessment of patients with
      non-traumatic chest pain.

PMID- 23877494
TI  - [Nurses' decisions in the care of advanced dementia patients: a survey].
AB  - INTRODUCTION: The aim of treatment for most dementia patients should be comfort,
      symptoms control and withholding of futile or invasive treatments. AIM: To
      describe the decision of Nursing Home (NH) nurses towards some critical
      situations for advanced dementia patients. METHODS: A questionnaire with 7
      clinical cases was administered to the nurses of 7 Italian NHs. The cases
      described a common or exemplar situation in an advanced dementia patient (FAST
      stage >7a) and limited life expectation. For each case the 4 closed ended
      questions described a behavior oriented to comfort (one answer) or aggressive
      treatment (3 answers). RESULTS: Sixty-three/92 nurses (68.5%) answered the
      questionnaire. The majority (39, 61.9%) would feed the patient until death; 53
      (84.1%) would favor hospital admission or resuscitation attempts while 55 (87.3%)
      would administer antibiotics for pneumonia even without distressing symptoms.
      With an expected survival <15 days 34 (54%) would favor a terminal sedation with
      refractory symptoms and 35 (55.6%) would stop unnecessary treatments (only 4
      would prefer subcutaneous route). Thirty-two nurses (50.8%) would assess pain
      while 28 (44.4%) would contain an agitated patient. Continuing education is
      associated to cestrain behaviors, specifically for sedation (p 0.01) and revision
      of drug regimens (p 0.05). CONCLUSIONS: Nurses are not fully competent in
      providing palliative care. Due to the impact of education, courses should be
      developed to improve the care of the dying and make nurses aware of the natural
      course of dementia.

PMID- 23877495
TI  - [Phosphate containing enemas: one undervalued risky practice? The management of
      an adverse event].
AB  - INTRODUCTION: The phosphate-containing enemas are widely used, both to manage
      constipation and as a preparation for endoscopic procedures and surgery in adults
      and children. Many studies report that the use of these laxatives can be
      dangerous. OBJECTIVE: To identify possible prevention strategies starting from a
      severe adverse reaction due to repeated administrations of phosphate enemas.
      METHODS: A working group was started, the literature was reviewed and
      recommendations for an appropriate use of enemas were discussed and implemented,
      to improve patients' safety. RESULTS: Phosphate-containing enemas were replaced
      with 125 ml water enemas; recommendations were spread to strongly limit the use
      of phosphate containing enemas and the use of laxative in the first and second
      semester of 2012, were confronted showing a change in habits and a reduction in
      the use of phosphate containing enemas. CONCLUSIONS: The implementation of
      several strategies, originated from an adverse event, succeeded in modifying the
      use of laxatives and phosphate-containing enemas.

PMID- 23877496
TI  - [Risk and causalty in environmental disasters].
AB  - A Dossier dedicated to environmental issues is a rare but important event in the
      history of AI&R. Environmental issues (and even more specific health related
      risks and severe events with morbidity-mortality outcomes) are hardly, or at best
      marginally part of the basic training of the medical and nursing professionals. A
      clear indicator of the otherness of these problems, with respect to the culture
      and competences which guide routine practice, is the very difficult, and
      therefore rare, possibility of the use of medical records for the production of
      timely and/or periodical scientific-epidemiological reports. The Dossier (to be
      closely linked and integrated with the Editorial, is principally based on two
      major disasters which have even occupied the national and international
      chronicles over at least the last few years: the thousands of workers and
      community victims of asbestos in Casale Monferrato; the area-wide and decades
      long exposure to chemical industrial pollution of the workers and population of
      Taranto. The cases are presented with a combination of narrative testimonies of
      professionals and lay witness of the two scenarios, and essential epidemiological
      data, which refer to the original, abundant documents and publications. Because
      of its critical and specific importance and controversial character, the issue of
      juridical criminal responsibility is discussed, technically but didactically by
      an expert who has been directly involved with the cases. Two apparently atypical
      but, in fact, strictly complementary contributions conclude the Dossier,
      recalling the need of extending the meaning of environmental variables, on one
      side to the broader socioeconomic context, on the other to the highly personal
      (professional and human) experiences met in crossing one of the most described
      but substantially ignored faces of the diseased cultural and physical environment
      in the South.

PMID- 23877498
TI  - Orthogonal interactions between nitryl derivatives and electron donors: pnictogen
      bonds.
AB  - Pnictogen complexes between nitryl derivatives (NO2X, X = CN, F, Cl, Br, NO2, OH,
      CCH, and C2H3) and molecules acting as Lewis bases (H2O, H3N, CO, HCN, HNC and
      HCCH) have been obtained at the MP2/aug-cc-pVTZ computational level. A total of
      53 minima have been located. Their energy, geometry, DFT-SAPT energy terms,
      electronic properties (NBO, AIM, ELF, and NCI) and NMR shieldings have been
      calculated and analyzed. Finally, a search in the CSD database has been carried
      out, showing a large number of similar interactions in crystallographic
      structures. 

PMID- 23877499
TI  - Stem cells: Signalling to DNA methylation.

PMID- 23877500
TI  - Genome stability: Specialist responses at telomeres.

PMID- 23877501
TI  - Osteogenesis imperfecta--a human temporal bone case study.

PMID- 23877502
TI  - Pre- and postnatal imaging of early cerebral damage in Sturge-Weber syndrome.
AB  - A case of prenatal diagnosis of Sturge-Weber syndrome associated with
      polymicrogyria is reported. The diagnosis was based on a unique association with
      unilateral hemispheric gyriform calcification, focal hemispheric atrophy and
      white matter changes on prenatal imaging including ultrasound and MRI.
      Polymicrogyria, which is exceptionally associated with Sturge-Weber syndrome, is
      suggestive of and reinforces the hypothesis of early impairment of the cerebral
      microvasculature related to leptomeningeal angioma, which may lead to abnormal
      cerebral development as early as the second trimester of pregnancy. 

PMID- 23877503
TI  - Ganglion cysts in the paediatric wrist: magnetic resonance imaging findings.
AB  - BACKGROUND: The majority of published literature on ganglion cysts in children
      has been from a surgical perspective, with no dedicated radiologic study yet
      performed. OBJECTIVE: Our aim was to assess the magnetic resonance (MR) imaging
      appearance of ganglion cysts in a series of paediatric MR wrist examinations.
      MATERIALS AND METHODS: Ninety-seven consecutive paediatric MR wrist examinations
      were retrospectively reviewed for the presence of ganglion cysts. Only those
      studies with wrist ganglia were included. Cysts were assessed for location, size,
      internal characteristics and secondary effect(s). RESULTS: Forty-one ganglion
      cysts (2-32 mm in size) were seen in 35/97 (36%) patients (24 female, 11 male),
      mean age: 13 years 11 months (range: 6 years 3 months-18 years). The majority
      were palmar (63.4%) with the remainder dorsal. Of the cysts, 43.9% were related
      to a wrist ligament(s), 36.6% to a joint and 17.1% to the triangular
      fibrocartilage complex. Of the patients, 91.4% had wrist symptoms: pain (n=29,
      82.9%), swelling (n=7, 20%) and/or palpable mass (n=4, 11.4%); 71.4% patients had
      significant additional wrist abnormalities. CONCLUSION: Ganglion cysts were
      frequently found in children referred for wrist MRI.

PMID- 23877504
TI  - Driving down daily step counts: the impact of being driven to school on physical
      activity and sedentary behavior.
AB  - This study investigated whether being driven to school was associated with lower
      weekday and weekend step counts, less active out-of-school leisure pursuits, and
      more sedentary behavior. Boys aged 10-13 years (n = 384) and girls aged 9-13
      years (n = 500) attending 25 Australian primary schools wore a pedometer and
      completed a travel diary for one week. Parents and children completed surveys
      capturing leisure activity, screen time, and sociodemographics. Commute distance
      was objectively measured. Car travel was the most frequent mode of school
      transportation (boys: 51%, girls: 58%). After adjustment (sociodemographics,
      commute distance, and school clustering) children who were driven recorded fewer
      weekday steps than those who walked (girls: -1,393 steps p < .001, boys: -1,569
      steps, p = .009) and participated in fewer active leisure activities (girls only:
      p = .043). There were no differences in weekend steps or screen time. Being
      driven to and from school is associated with less weekday pedometer-determined
      physical activity in 9- to 13-year-old elementary-school children. Encouraging
      children, especially girls, to walk to and from school (even for part of the way
      for those living further distances) could protect the health and well-being of
      those children who are insufficiently active. 

PMID- 23877506
TI  - Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy
      or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid:
      a pilot comparison.
AB  - PURPOSE OF THE REPORT: The standard thyroid functional imaging method, 99mTc
      pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing
      its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking
      these disadvantages and allowing simultaneous CT, may have greater sensitivity
      for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT)
      versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT
      single-photon emission CT (SPECT), in characterizing the thyroid gland with
      benign disease. PATIENTS AND METHODS: Twenty-one consecutive adults with goiter
      underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT
      planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of "hot
      spots" with/without central photopenia and "cold spots" detected, the proportion
      of these lesions with morphological correlates, the mean volume and diameter of
      visualized nodules, and the number of cases of lobus pyramidalis or retrosternal
      thyroid tissue identified. RESULTS: 124I-PET detected significantly more "hot
      spots" with/without central photopenia (P < 0.001), significantly more nodules (P
      < 0.001), and more "cold spots" than did 99mTc-PT planar scintigraphy or 99mTc-PT
      SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic
      correlates were found for all nodules visualized on all 3 modalities and 92.5% of
      nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had
      significantly smaller mean volume or diameter (P < 0.001) than did those
      visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT)
      identified significantly more patients with a lobus pyramidalis (P < 0.001) or
      retrosternal thyroid tissue (P < 0.05). CONCLUSIONS: 124I-PET(/CT) may provide
      superior imaging of benign thyroid disease compared to planar or cross-sectional
      99mTc-PT scintigraphy.

PMID- 23877505
TI  - Chronic peripheral administration of kappa-opioid receptor antagonist advances
      puberty onset associated with acceleration of pulsatile luteinizing hormone
      secretion in female rats.
AB  - Puberty in mammals is timed by an increase in gonadotropin-releasing hormone
      (GnRH) secretion. Previous studies have shown involvement of the two
      neuropeptides, kisspeptin and neurokinin B (NKB), in controlling puberty onset.
      Little is known about the role of the other key neuropeptide, dynorphin, in
      controlling puberty onset, although these three neuropeptides colocalize in the
      arcuate kisspeptin neurons. The arcuate kisspeptin neuron, which is also referred
      to as the KNDy neuron, has recently been considered to play a role as an
      intrinsic source of the GnRH pulse generator. The present study aimed to
      determine if attenuation of inhibitory dynorphin-kappa-opioid receptor (KOR)
      signaling triggers the initiation of puberty in normal developing female rats.
      The present study also determined if stimulatory NKB-neurokinin 3 receptor (NK3R)
      signaling advances puberty onset. Female Wistar-Imamichi rats were weaned and
      intraperitoneally implanted with osmotic minipumps filled with nor
      binaltorphimine (nor-BNI), a KOR antagonist, or senktide, a NK3R agonist, at 20
      days of age. Fourteen days of intraperitoneal infusion of nor-BNI or senktide
      advanced puberty onset, manifested as vaginal opening and the first vaginal
      estrus in female rats. Frequent blood sampling showed that nor-BNI significantly
      increased luteinizing hormone (LH) pulse frequency at 29 days of age compared
      with vehicle-treated controls. Senktide tended to increase this frequency, but
      its effect was not statistically significant. The present results suggest that
      the inhibitory input of dynorphin-KOR signaling plays a role in the prepubertal
      restraint of GnRH/LH secretion in normal developing female rats and that
      attenuation of dynorphin-KOR signaling and increase in NKB-NK3R signaling trigger
      the onset of puberty in female rats. 

PMID- 23877507
TI  - Extraskeletal intraspinal mesenchymal chondrosarcoma; 18F-FDG PET/CT finding.
AB  - Mesenchymal chondrosarcoma is a rare and aggressive form of chondrosarcoma. The
      extraskeletal intraspinal type is even rare among the mesenchymal chondrosarcoma
      cases. We presented a case of a 17-year-old boy pathologically diagnosed with
      intraspinal mesenchymal chondrosarcoma. MRI showed multiple intradural
      extramedullary masses with contrast enhancement, without the evidence of brain
      lesion. On F-FDG PET/CT, hypermetabolism was observed in the lesions matched with
      enhancement on spine MRI. The lesions were well differentiated from spinal cord.
      In the case of hypermetabolic lesion in intradural and extramedullary lesion of
      the spinal cord, mesenchymal chondrosarcoma should be considered for the
      differential diagnosis. 

PMID- 23877508
TI  - The incidental suggestive meningioma presenting as high 18F FP-CIT uptake on
      PET/CT study.
AB  - A 76-year-old woman with about a 13-month history of bradykinesia, gait
      disturbance and resting tremor of right upper extremity was referred to Nuclear
      Medicine Department. A PET-CT with 229 MBq of F FP-CIT was performed to diagnose
      suspected early Parkinson's disease (PD). The PET-CT showed a mass lesion with
      highly intense focal dopamine transporter uptake in the right frontal lobe. A
      subsequent brain magnetic resonance image also showed a mass in the right frontal
      lobe demonstrating homogeneous enhancement and extensive surrounding edema,
      highly suggestive of a brain tumor. 

PMID- 23877509
TI  - Increased FDG uptake of heterotopic pancreatitis in the stomach.
AB  - Heterotopic pancreas is the presence of pancreatic tissue lying outside of its
      normal location and lacking anatomic or vascular connections with the pancreas.
      Heterotopic pancreas can undergo inflammatory changes similar to the normal
      pancreatic gland. We present 2 rare cases showing increased (18)F-FDG uptake in
      the heterotopic pancreatitis of the stomachs. To our knowledge, heterotopic
      pancreatitis with increased tracer accumulation on FDG PET/CT has not been
      reported before. Heterotopic pancreas should be included in the differential
      diagnosis of abnormal gastric FDG accumulation along with tumor and infectious
      processes.

PMID- 23877510
TI  - Unexpected detection of brain metastases by 18F-NaF PET/CT in a patient with lung
      cancer.
AB  - In recent years, the inconsistent supply of (99m)Tc and the increasingly
      widespread use of PET/CT have led to a renewed interest in PET/CT bone scans
      using (18)F-NaF. Recently, a 64-year-old man with biopsy-proven lung cancer
      underwent an (18)F-NaF PET/CT bone scan due to a shortage of (99m)Tc.
      Unexpectedly, multiple nodular foci of increased tracer uptake were present in
      the brain, whereas there were no definitive bone metastases detected.
      Subsequently, brain MRI confirmed the presence of brain metastases.

PMID- 23877511
TI  - Fused 99mTc-HDP SPECT/MR imaging of reverse Hill-Sachs deformity.
AB  - Reverse Hill-Sachs deformity is a term for a linear impression fracture of the
      anteromedial humeral head caused by a posterior shoulder dislocation, which is an
      extremely rare subtype of shoulder dislocations and caused by an epileptic
      seizure, an electric shock or trauma. Herein, we illustrate the findings of bone
      pinhole study, MRI and fused SPECT/MR imaging of reverse Hill-Sachs deformity
      caused by posterior shoulder dislocation after motor cycle accident in a 41-year
      old man. 

PMID- 23877512
TI  - False-positive 123I-FP-CIT scintigraphy and suggested dopamine transporter
      upregulation due to chronic modafinil treatment.
AB  - A 76-year-old man with movement disorder had a I-FP-CIT (DaTSCAN) SPECT exam
      demonstrating universally decreased striatal uptake. It was later determined that
      he had taken modafinil, and the scintigraphy was interpreted as false positive.
      Because of progressive symptoms, DaTSCAN was repeated 43 months later, with
      modafinil withheld for 7 days. Striatal uptake values were nearly doubled
      compared with the modafinil state and were now above normal upper limit. This
      suggests pharmacological upregulation of dopamine transport capacity by chronic
      modafinil treatment. In this setting, I-FP-CIT striatal uptake values should be
      interpreted with caution. 

PMID- 23877513
TI  - 18F-FDG PET/CT and MRI of necrobiotic xanthogranuloma.
AB  - Necrobiotic xanthogranuloma is a non-Langerhans histiocytic disorder
      characterized by chronic and progressively enlarging cutaneous plaques and
      nodules predominantly at the head and facial regions. These lesions exhibit
      increased F-FDG uptake because of their inflammatory and granulomatous nature.
      The author presents the F-FDG PET/CT and MRI features of such an uncommon disease
      in a patient with associated monoclonal gammopathy. 

PMID- 23877514
TI  - Imaging of intravenous lobular capillary hemangioma of azygos vein.
AB  - Intraluminal masses of the azygos vein are of rare occurrence. The differential
      diagnosis includes bland thrombus, tumor thrombus, epithelioid
      hemangioendothelioma, and leiomyosarcoma. To this list, the authors add an
      uncommon case of intravenous lobular capillary hemangioma, also known as
      intravenous pyogenic granuloma, of the azygos vein, inducing a recurrent large
      right pleural effusion. CT, MR, and PET/CT features of this lesion are presented.

PMID- 23877516
TI  - FDG PET/CT in peripheral primitive neuroectodermal tumor of the retroperitoneum.
AB  - Peripheral primitive neuroectodermal tumor (pPNET) is a very aggressive neoplasm
      that predominantly affects children and adolescents with a poor prognosis. A 35
      year-old woman presented with right upper abdominal pain for 2 weeks. Abdominal
      enhanced CT showed a large cystic-solid tumor in the left retroperitoneum, with
      progressive enhanced papillary projections of the wall. FDG PET/CT showed strong
      FDG uptake of the cystic wall with SUVmax of 17.2. The patient underwent
      completed resection of the tumor. pPNET was confirmed by pathology. The high FDG
      uptake of the tumor may be related to its high proliferative index revealed by Ki
      67. 

PMID- 23877515
TI  - Bone marrow metastases in an otherwise operable gall bladder cancer: rare site of
      distant metastases detected on FDG PET/CT.
AB  - Primary carcinoma of gall bladder is a highly aggressive malignancy, most often
      detected in late stage in majority of the affected patients. It commonly spreads
      to the adjacent liver parenchyma and, via lymphatics, to mesenteric nodes. Extra
      abdominal metastatic sites are extremely rare, with lung being the commonest
      site. We report a rare occurrence of isolated asymptomatic bone marrow metastases
      from gall bladder cancer, in the absence of locoregional adenopathy, detected on
      whole-body F-FDG PET/CT at initial staging. 

PMID- 23877517
TI  - Fireworks-induced chest wall granulomatous disease: 18F-FDG PET/CT imaging.
AB  - The authors present a case of 18F-FDG-avid granulomatous reaction induced by
      fireworks injury of the chest wall in a patient with esophageal adenocarcinoma.
      This hypermetabolic lesion, involving the right pectoralis muscles, appeared
      slightly more prominent on restaging PET/CT imaging following chemotherapy and
      radiation therapy. Excisional biopsy of the lesion established the diagnosis of
      foreign-body granulomatous-type inflammation with surrounding foci of non
      polarizable black foreign material and ruled out malignancy. The patient recalled
      accidentally shooting himself in the chest with a Roman candle at the age of 3.

PMID- 23877518
TI  - Acute gangrenous cholecystitis diagnosed on gallium scan.
AB  - A 72-year-old male patient was hospitalized with diffused abdominal pain with
      worsening renal insufficiency, intermittent vomiting, and a spiking fever.
      Initial CT scan and sonography showed a dilated gallbladder with a polyp, but no
      calculi. A gallium scan with SPECT/CT revealed intense gallbladder uptake with a
      cold central area. Acute gangrenous cholecystitis was suspected as the likely
      diagnosis and cause of his discomfort and fever. Subsequent cholecystectomy
      confirmed the diagnosis. 

PMID- 23877519
TI  - A rare case of synchronous fetal type adenocarcinoma and mucinous adenocarcinoma
      of the lung evaluated by 18F-FDG PET/CT.
AB  - A 71-year-old man underwent F-FDG PET/CT for metabolic characterization of
      pulmonary nodules. F-FDG PET/CT showed increased tracer uptake in a 3.5-cm left
      upper lobe mass. A second lesion (1.5 cm) characterized by poor F-FDG uptake was
      described in the same lobe. Based on these findings, the patient underwent upper
      left lobectomy. Histology demonstrated 2 synchronous tumors. The F-FDG-avid
      lesion was a rare moderately differentiated fetal type adenocarcinoma, whereas
      the second lesion with low F-FDG uptake was a moderately differentiated mucinous
      adenocarcinoma. In our case, F-FDG PET/CT has been useful in metabolic
      characterization and staging of these synchronous rare pulmonary tumors. 

PMID- 23877520
TI  - Role of SPECT/CT in sentinel lymph node detection in patients with breast cancer.
AB  - AIM: The purpose of this study was to conduct a systematic review of the
      published literature to assess the role (indications, advantages, and
      limitations) of SPECT/CT for the detection of sentinel lymph node (SLN) in breast
      cancer. METHODS: The authors searched PubMed for published literature in English
      addressing this topic. RESULTS: Eleven studies, published since 2006, focused on
      the role and value of SPECT/CT for SLN detection (SLND). They showed that
      SPECT/CT improved sentinel node detection and anatomical localization. One study
      suggested that SPECT/CT may provide a more accurate staging. Limitations for SLND
      with SPECT/CT include extra time and inconvenience for the patient and additional
      radiation dose. CONCLUSIONS: SPECT/CT is a valuable tool for SLND, especially in
      difficult cases, when planar lymphoscintigraphy shows no SLN or unexpected
      lymphatic drainage.

PMID- 23877521
TI  - Squamous cell carcinoma of the prostate with strong FDG uptake on PET/CT.
AB  - Primary squamous cell carcinoma (SCC) of the prostate is a rare aggressive
      neoplasm with a poor prognosis. A 60-year-old man presented with urinary
      frequency and interrupted urination for 4 months. Serum prostate-specific antigen
      and SCC antigen were elevated. T2-weighted MR images showed a hyperintense lesion
      in the central area of the prostate. FDG PET/CT showed strong FDG uptake of the
      lesion with SUVmax of 15.5. Prostate biopsy revealed moderate differentiated SCC.
      This case indicates SCC of the prostate should be considered in the differential
      diagnosis of abnormal prostate FDG accumulation (especially with elevated SCC
      antigen level). 

PMID- 23877522
TI  - 68Ga-DOTANOC PET/CT imaging in glomus laryngicum.
AB  - Glomus laryngicum (laryngeal paraganglioma) are extremely rare neoplasm of the
      larynx. We here present the 68Ga-DOTANOC PET/CT images of a 40-year-old male
      patient with glomus laryngicum. In this report, we have highlighted the potential
      utility and limitations of 68Ga-DOTANOC PET/CT imaging in patients with glomus
      laryngicum.

PMID- 23877523
TI  - Increased FDG uptake of the bone marrow mimicking malignancy in a patient of
      eosinophilia secondary to Sparganum mansoni infection.
AB  - Secondary eosinophilia is usually associated with parasitosis in Third World
      countries. We present a case of eosinophilia secondary to Sparganum mansoni
      infection showing multifocal FDG uptake in the axial bones mimicking malignancy.
      Bone marrow aspirations and biopsy revealed remarkable proliferation of
      eosinophils which may be related to the increased FDG uptake. This case indicates
      that secondary eosinophilia associated with parasitosis may be one cause of
      diffuse FDG uptake in the bone marrow. 

PMID- 23877524
TI  - Focal fat sparing of the liver: a nonmalignant cause of focal FDG uptake on FDG
      PET/CT.
AB  - Fat spared area of liver can appear as focal areas of elevated FDG uptake on a
      PET scan. This may mimic metastases. PET scan performed for metastatic workup in
      a 35-year-old female patient, a case of exocrine tumor of the pancreas, showed
      focal areas of increased FDG uptake. Contrast-enhanced CT performed as a part of
      the PET/CT study showed enlarged fatty liver with focal hyperdense areas
      suggesting fat sparing. Sulfur colloid scan showed physiological colloid uptake
      in the suspicious areas indicating preserved Kupffer cell function. The patient
      is on close follow-up without any evidence of metastatic disease. 

PMID- 23877525
TI  - Asymmetric (99m)Tc-MDP uptake in mineralized tendons might mimic bone lesions:
      heterotopic tendon mineralization on a (99m)Tc-MDP bone scan and a (18)F-FDG
      PET/CT scan.
AB  - A 55-year-old man was a hepatocellular carcinoma patient, diagnosed by sonography
      and a biopsy. Because of his musculoskeletal tenderness, a bone scan was
      performed to exclude skeletal metastasis. A subsequent F-FDG PET/CT scan revealed
      that the unilateral abnormal uptake seen on the bone scan was actually a
      mineralized tendon. A mineralized tendon is easily detectable using Tc-MDP;
      therefore, it is imperative to differentiate between bone lesions and mineralized
      tendons. In addition, few studies have reported F-FDG uptake in a calcified
      tendon. 

PMID- 23877526
TI  - Tips for a physician in getting the right job part III: Networking and social
      media, references, and recruiters.
AB  - It is important that physicians are appropriately aggressive in obtaining the
      best possible job, and not sitting back passively and expecting employers to come
      hunting for them. Networking is very important to learn of new job opportunities
      and in some cases to be introduced to prospective employers. Social media sites
      may be useful for networking and for researching job opportunities and the people
      in certain organizations. Recruiters can be helpful for many physicians in
      finding the right job. However, some recruiters can be bothersome and be more
      interested in making a commission than in obtaining the best match between the
      employer and employee. Having stellar references who will give an enthusiastic
      recommendation for the job seeker, both in writing and on the phone, is very
      important. 

PMID- 23877527
TI  - Chemotherapy-related gallbladder visualization in a 99mTc-HMDP SPECT/CT bone
      scan.
AB  - Nonosseous uptakes are occasionally found on bone scintigraphy. Most of them are
      easily explained by current pathophysiological mechanisms (metastatic
      calcifications, metabolic process, or extravascular accumulation of
      radiopharmaceutical) or current artifacts. Other unusual findings are still
      unexplained. We report 1 didactic case of incidental gallbladder uptake on bone
      scan. Additional single-photon emission computed tomography-computed tomography
      (SPECT/CT) imaging was performed to better characterize abnormal location. The
      significance of this serendipitous uptake is not clearly established. This
      finding could be due to altered distribution induced by the chemotherapy regimen
      and is not the result of intrinsic gallbladder disease. 

PMID- 23877528
TI  - Increased 177Lu-DOTATATE uptake in Paget disease.
AB  - A 45-year-old female patient was referred for peptide receptor radionuclide
      therapy of liver metastases of neuroendocrine origin; the patient had undergone 2
      years earlier surgical resection of a grade 2 neuroendocrine neoplasm of ampulla
      of Vater infiltrating the duodenal submucosa and muscular layers and the
      neighboring pancreatic tissue. Post-therapy whole-body scan performed to evaluate
      in vivo radiopharmaceutical distribution confirmed high accumulation in liver
      lesions and revealed increased uptake in the hip bone. Bone scan and
      corresponding CT images demonstrated changes of Paget disease in the same
      district. 

PMID- 23877529
TI  - Evaluation of rare choroid plexus metastasis from papillary thyroid carcinoma
      with multimodality imaging.
AB  - Papillary thyroid carcinoma (PTC) is the most common malignancy of thyroid gland.
      Though it metastasizes primarily through lymphatics, hematogenous spread is not
      infrequent. We report the case of a 62-year-old male patient with
      intraventricular choroid plexus metastasis from PTC, incidentally detected on
      post-high-dose radioiodine therapy whole-body I scan, which is an extremely rare
      presentation. Only 3 cases of choroid plexus metastasis from thyroid carcinoma
      have been reported. Further multimodality radiological investigations confirmed
      diagnosis and helped in assessing treatment response. The patient received gamma
      knife stereotactic radiosurgery, and follow-up radiological imaging suggested
      improvement of intracranial metastasis. 

PMID- 23877530
TI  - "Due" for a scan: examining the utility of monitoring densitometry.

PMID- 23877531
TI  - Gut microbiota: Selecting Clostridia strains that induce TREG cells from gut
      microbiota.

PMID- 23877532
TI  - Liver disease: Kupffer cells regulate the progression of ALD and NAFLD.

PMID- 23877533
TI  - Linking ecosystem services and human health: the Eco-Health Relationship Browser.
AB  - OBJECTIVES: Ecosystems provide multiple services, many of which are linked to
      positive health outcomes. Review objectives were to identify the set of
      literature related to this research topic, and to design an interactive, web
      based tool highlighting the weight of evidence, thus making the information more
      accessible. METHODS: A systematic review was conducted to create the Eco-Health
      Relationship Browser (
      http://www.epa.gov/research/healthscience/browser/introduction.html ). The search
      was conducted in four stages utilizing Google Scholar, PubMed and Science Direct,
      targeted journals, and targeted keywords; search results were limited to peer
      reviewed journal articles published in English from 1 January 1990 to 31 December
      2012. RESULTS: The review identified 344 relevant articles; a subset of 169
      articles was included in the Browser. Articles retrieved during the search
      focused on the buffering and health-promotional aspects of ecosystem services.
      Landscape and Urban Planning, Urban Forestry and Urban Greening, and Health and
      Place yielded the most articles relevant to this search. CONCLUSIONS: Results
      from the systematic review were used to populate the Browser, which organizes the
      diverse literature and allows users to visualize the numerous connections between
      ecosystem services and human health.

PMID- 23877534
TI  - Systematic review of reducing population meat consumption to reduce greenhouse
      gas emissions and obtain health benefits: effectiveness and models assessments.
AB  - OBJECTIVES: This review evaluates existing co-benefit models for emission and
      health outcomes of counterfactual scenarios of reduced meat consumption at a
      population level. METHODS: A novel assessment process was developed, combining
      selected measures from the Cochrane Review quality assessment tools, from the
      PRISMA checklist, and model quality measures identified by the authors during the
      preliminary phases of the review process. RESULTS: Four emission models and three
      health outcome models have been identified which show great variation in model
      characteristics and qualities. The estimated counterfactual scenario emission
      effects presented in the included studies ranged from a reduction of <3-30 % and
      reduction in the burden of disease ranged from 1 to 16 %. Meta-analysis could not
      be conducted due to high heterogeneity of model characteristics. CONCLUSIONS: All
      co-benefit studies estimated that reducing population meat consumption could
      reduce greenhouse gas emissions and the burden of disease. However, important
      attention must be paid to nutrition balance and a systematic approach in input
      and output attribute parameters is recommended for better model quality.

PMID- 23877535
TI  - Environmental cadmium exposure and osteoporosis: a review.
AB  - OBJECTIVES: To review the published literature investigating the association
      between cadmium exposure and osteoporosis. METHODS: A review of published peer
      reviewed literature based on a priori criteria was completed. Odds ratios (OR)
      were abstracted or estimated from observational studies to calculate a pooled OR
      using inverse variance weighted random effects models. RESULTS: The review
      identified seven studies with a pooled OR of OR = 2.22 (95 % CI: 1.16, 4.28) [I
      (2) = 54.8 % (p < 0.05)] (comparing highest urine cadmium category to lowest). In
      women over the age of 50 years, the pooled OR was 1.82 (95 % CI: 1.63, 2.02) [I
      (2) = 73.1 % (p < 0.05)]. A dose response evaluation (six studies) suggested
      increasing odds for osteoporosis with increasing urine cadmium levels.
      CONCLUSIONS: This review detected an association between cadmium exposure and the
      occurrence of osteoporosis in a small number of cross-sectional studies which
      requires confirmation in using prospective study design.

PMID- 23877536
TI  - Can 8-hydroxy-2'-deoxyguanosine be used to assess oxidative stress caused by
      particulate matter air pollution in the general population?
AB  - OBJECTIVES: Assess the association between 8-hydroxy-2'-deoxyguanosine (8OHdG)
      levels and particulate matter air pollution in non-occupational exposure groups
      from peer-reviewed literature. METHODS: Ovid Medline and PubMed were used to
      search for all peer-reviewed articles published between 1946 and May 2013.
      Keywords included particulate matter, air pollution, deoxyguanosine, 8-hydroxy-2'
      deoxyguanosine, and known abbreviations. Seven English, non-occupational
      exposure, human subject studies were evaluated. RESULTS: Of the two studies
      involving children one found significant positive associations between exposure
      to particulate matter air pollution and 8OHdG. Investigations into non
      occupationally exposed adults were mixed. The lone double-blind crossover study
      found no relationship between diesel exhaust exposure and 8OHdG. Two out of three
      panel studies and one cohort study found significant associations between 8OHdG
      and classes of particles and for various lags. CONCLUSIONS: Analyses accounting
      for particle composition and lags between exposure and physiological responses
      had the strongest significant associations. Results are not conclusive due to the
      inconsistency in study designs, small sample sizes, and differences in exposure
      assessment techniques. Consistent methodology with representative populations
      including women and other non-occupationally exposed groups are recommended.

PMID- 23877537
TI  - How to exploit twitter for public health monitoring?
AB  - OBJECTIVES: Detecting hints to public health threats as early as possible is
      crucial to prevent harm from the population. However, many disease surveillance
      strategies rely upon data whose collection requires explicit reporting (data
      transmitted from hospitals, laboratories or physicians). Collecting reports takes
      time so that the reaction time grows. Moreover, context information on individual
      cases is often lost in the collection process. This paper describes a system that
      tries to address these limitations by processing social media for identifying
      information on public health threats. The primary objective is to study the
      usefulness of the approach for supporting the monitoring of a population's health
      status. METHODS: The developed system works in three main steps: Data from
      Twitter, blogs, and forums as well as from TV and radio channels are continuously
      collected and filtered by means of keyword lists. Sentences of relevant texts are
      classified relevant or irrelevant using a binary classifier based on support
      vector machines. By means of statistical methods known from biosurveillance, the
      relevant sentences are further analyzed and signals are generated automatically
      when unexpected behavior is detected. From the generated signals a subset is
      selected for presentation to a user by matching with user queries or profiles. In
      a set of evaluation experiments, public health experts assessed the generated
      signals with respect to correctness and relevancy. In particular, it was assessed
      how many relevant and irrelevant signals are generated during a specific time
      period. RESULTS: The experiments show that the system provides information on
      health events identified in social media. Signals are mainly generated from
      Twitter messages posted by news agencies. Personal tweets, i.e. tweets from
      persons observing some symptoms, only play a minor role for signal generation
      given a limited volume of relevant messages. Relevant signals referring to real
      world outbreaks were generated by the system and monitored by epidemiologists for
      example during the European football championship. But, the number of relevant
      signals among generated signals is still very small: The different experiments
      yielded a proportion between 5 and 20% of signals regarded as "relevant" by the
      users. Vaccination or education campaigns communicated via Twitter as well as use
      of medical terms in other contexts than for outbreak reporting led to the
      generation of irrelevant signals. CONCLUSIONS: The aggregation of information
      into signals results in a reduction of monitoring effort compared to other
      existing systems. Against expectations, only few messages are of personal nature,
      reporting on personal symptoms. Instead, media reports are distributed over
      social media channels. Despite the high percentage of irrelevant signals
      generated by the system, the users reported that the effort in monitoring
      aggregated information in form of signals is less demanding than monitoring huge
      social-media data streams manually. It remains for the future to develop
      strategies for reducing false alarms.

PMID- 23877538
TI  - Fast detection of oxygen by the naked eye using a stable metal-organic framework
      containing methyl viologen cations.
AB  - A stable porous metal-organic framework (MOF) containing methyl viologen cations
      exhibits reversible photochromic, thermochromic and fluorescence changes via host
      guest interactions, and can be used for fast and selective detection of oxygen by
      naked eye recognition of color change within five seconds. 

PMID- 23877539
TI  - Individuals with congenital amusia imitate pitches more accurately in singing
      than in speaking: implications for music and language processing.
AB  - In this study, we investigated the impact of congenital amusia, a disorder of
      musical processing, on speech and song imitation in speakers of a tone language,
      Mandarin. A group of 13 Mandarin-speaking individuals with congenital amusia and
      13 matched controls were recorded while imitating a set of speech and two sets of
      song stimuli with varying pitch and rhythm patterns. The results indicated that
      individuals with congenital amusia were worse than controls in both speech and
      song imitation, in terms of both pitch matching (absolute and relative) and
      rhythm matching (relative time and number of time errors). Like the controls,
      individuals with congenital amusia achieved better absolute and relative pitch
      matching and made fewer pitch interval and contour errors in song than in speech
      imitation. These findings point toward domain-general pitch (and time) production
      deficits in congenital amusia, suggesting the presence of shared pitch production
      mechanisms but distinct requirements for pitch-matching accuracy in language and
      music processing. 

PMID- 23877540
TI  - Inhibition of return is at the midpoint of simultaneous cues.
AB  - When multiple cues are presented simultaneously, Klein, Christie, and Morris
      (Psychonomic Bulletin & Review 12:295-300, 2005) found a gradient of inhibition
      (of return, IOR), with the slowest simple manual detection responses occurring to
      targets in the direction of the center of gravity of the cues. Here, we explored
      the possibility of extending this finding to the saccade response modality, using
      methods of data analysis that allowed us to consider the relative contributions
      of the distance from the target to the center of gravity of the array of cues and
      the nearest element in the cue array. We discovered that the bulk of the IOR
      effect with multiple cues, in both the previous and present studies, can be
      explained by the distance between the target and the center of gravity of the cue
      array. The present results are consistent with the proposal advanced by Klein et
      al., (2005) suggesting that this IOR effect is due to population coding in the
      oculomotor pathways (e.g., the superior colliculus) driving the eye movement
      system toward the center of gravity of the cued array. 

PMID- 23877541
TI  - Short-term effects on substance use of the keepin' it real pilot prevention
      program: linguistically adapted for youth in Jalisco, Mexico.
AB  - This article presents the short-term effects of a pilot study of keepin'it REAL
      (Mantente REAL) conducted in central Mexico by a binational team of
      investigators. This middle school-based model program for preventing substance
      use was adapted for Mexico linguistically but not culturally. Two Guadalajara
      public middle schools were recruited and randomly assigned to either implement
      the prevention program or serve as a control site. The program was implemented in
      the treatment site by the students' regular teachers, who were trained by the
      research team. Seventh graders in ten classrooms in the treatment and control
      schools (N = 432) completed a pretest and posttest survey in Spanish similar to
      the survey utilized in the original efficacy trial of keepin'it REAL in the US. T
      tests and OLS regressions were conducted to determine the effects of the
      intervention on substance use outcomes. Differences between treatment and control
      groups in frequency of use of alcohol and tobacco, the two substances of choice
      in this sample, were significant and in the desired direction. Differences in
      amount of use were also in the preferred direction but were not significant for
      alcohol and only marginally significant for tobacco. When the sample was split by
      gender, statistically significant treatment effects remained for females but were
      not observed among males. Effects of the linguistically adapted version of
      keepin'it REAL appears to be driven by the change in female use; however, the
      difference in male and female outcomes was not statistically significant.
      Implications for cultural adaptation and prevention in Mexico are discussed from
      a communication competency perspective. The promising results of the pilot study
      suggest that the linguistic adaptation was effective, but that a comprehensive
      cultural adaptation of keepin'it REAL in partnership with Mexican investigators
      and communities may be warranted. 

PMID- 23877542
TI  - Novel methylsulfonyl chalcones as potential antiproliferative drugs for human
      prostate cancer: involvement of the intrinsic pathway of apoptosis.
AB  - Limited success has been achieved in extending the survival of patients with
      metastatic and hormone-refractory prostate cancer (HRPC). There is a strong need
      for novel agents in the treatment and prevention of HRPC. In the present study,
      the apoptotic mechanism of action of RG003 (2'-hydroxy-4-methylsulfonylchalcone)
      and RG005 (4'-chloro-2'-hydroxy-4-methylsulfonylchalcone) in association with
      intracellular signalling pathways was investigated in the hormone-independent
      prostate carcinoma cells PC-3 and DU145. We showed that these compounds induced
      apoptosis through the intrinsic pathway but not through the extrinsic one. We
      showed that synthetic chalcones induced an activation of caspase-9 but not
      caspase-8 in PC-3 cells. Even if both chalcones induced apoptosis in PC-3 cells,
      a dominant effect of RG003 treatment was observed resulting in a disruption of
      ?psim, caspase-9 and caspase-3 activation, PARP cleavage and DNA fragmentation.
      Furthermore, in regard to our results, it is clear that the simultaneous
      inhibition of Akt and NF-kappaB signalling can significantly contribute to the
      anticancer effects of RG003 and RG005 in PC-3 prostate cancer cells. NF-kappaB
      inhibition was correlated with the reduction of COX-2 expression and induction of
      apoptosis. Our results clearly indicate for the first time that RG003 and RG005
      exert their potent anti-proliferative and pro-apoptotic effects through the
      modulation of Akt/NF-kappaB/COX-2 signal transduction pathways in PC-3 prostate
      cancer cells with a dominant effect for RG003. 

PMID- 23877544
TI  - Balloon dilatation of anastomotic strictures secondary to surgical repair of
      oesophageal atresia: a systematic review.
AB  - Surgical repair of oesophageal atresia may result in anastomotic strictures.
      These strictures are often treated by balloon dilatation (BD) and currently
      balloon dilatation (fluoroscopic or endoscopic) is the preferred primary
      treatment method. Here we review the current evidence of the outcomes of balloon
      dilatation of anastomotic strictures secondary to surgical repair of oesophageal
      atresia. We searched the standard databases (January, 1960-May, 2012) to identify
      all studies that reported outcomes of balloon dilatation of anastomotic
      strictures secondary to surgical repair of oesophageal atresia in children. Data,
      reported as median (range), were analysed and compared. Outcomes were success of
      BD, number of BD sessions, number of oesophageal perforations, need for other
      surgical interventions and mortality. Five studies were found to be relevant (n =
      139; 81 [58%] male children). The total number of dilatation sessions was 401
      (2.9 dilatations per child patient). General anaesthesia was used in two (40%)
      studies; sedation in a further two (40%) studies and one (20%) study used a
      combination of both. The size of balloon catheter ranged from 4 mm to 22 mm.
      Seven perforations were reported (1.8% per dilatation session), of which only one
      (14%) required surgery. No deaths were recorded. Balloon dilatation for
      anastomotic strictures post-EA repair is safe, and associated with a low
      perforation and mortality rates. Most perforations are amenable to conservative
      management.

PMID- 23877546
TI  - [The Freedom study].

PMID- 23877547
TI  - [Cardiovascular proteomics: challenges and opportunities for cardiologists of the
      future].
AB  - Proteomics is the study of the "proteome", that is the entire protein complement
      of a genome. However, it is well recognized that the proteome is far more complex
      than previously suggested by the "one-gene, one-protein" central dogma of
      biology. The proteome encompasses all proteins of a cell or organism at a given
      time, including not only those translated directly from genetic information but
      also the array of modified proteins arising from alternative splicing of
      transcripts and post-translational processing, resulting in modifications that
      have the potential to alter protein structure or biological function. As proteins
      are involved in virtually every cellular function, control every regulatory
      mechanism, and are modified in disease states, the proteome dictates the
      phenotype of the cell and, consequently, the tissue or organ that the cells
      comprise. This results in a dynamic, ongoing process of protein expression and
      modifications. The proteome thus consists of information from protein expression,
      post-translational modifications, processing and turnover, localization and time.
      Proteomics is aimed at identifying and characterizing these protein changes and,
      if applied to the field of cardiovascular sciences, it has the potential to
      reveal those proteins that are associated with pathogenesis and could be
      potentially used as predictive or prognostic markers. Cardioproteomic is still in
      its infancy and relatively few cardiovascular diseases have been investigated.
      However, it has enormously increased our knowledge of the complexity of the
      myocardium in terms of protein composition at cellular and organelle levels. The
      cardiac proteome is further complicated by protein post-translational
      modifications, which may regulate organelle function in physiological and
      pathological conditions. Therefore, the incorporation of proteomics into
      cardiovascular research will provide a means of exploring the mechanisms of
      disease onset and progression. This will in turn ultimately lead to increased
      efficiency of diagnosis and/or monitoring of treatment, which could dramatically
      increase the ability of the clinician to recognize cardiovascular disease states
      at a relatively early stage, and to improve the therapeutic approach. 

PMID- 23877548
TI  - [Controversial issues and working practice in myocarditis: from scientific data
      to clinical grounds].
AB  - Although the cause of myocarditis often remains unknown, a large variety of
      infections, systemic diseases, drugs and toxins have been associated with this
      disease. In most cases, myocarditis is induced by cardiotropic viruses and often
      evolves silently without discernible prognostic impact. However, in some
      patients, the lack of complete viral clearance and/or the association of a heart
      specific inflammation can cause persistent myocyte damage, ultimately leading to
      progressive myocardial dilation and dysfunction or life-threatening arrhythmias.
      Spontaneous improvement of left ventricular function is described for 40-50% of
      patients. The diagnostic work-up and prognostic assessment of myocarditis should
      be multiparametric and all available resources should be employed, i.e.
      biomarkers of myocardial damage and ventricular dysfunction (troponin I, brain
      natriuretic peptide), advanced echocardiography, cardiac magnetic resonance and,
      in selected cases, endomyocardial biopsy (with histopathologic,
      immunohistochemical and virological analyses). These are the necessary
      prerequisites for an evidence-based and personalized management of myocarditis,
      which may require in some cases specific immunoactive treatments. However,
      controversial issues regarding diagnosis (such as role and timing of cardiac
      magnetic resonance imaging, role of endomyocardial biopsy) and therapy of
      myocarditis still remain unsolved. The purpose of this review is to analyze these
      crucial features in order to provide useful instructions for clinical practice. 

PMID- 23877549
TI  - [Cardiovascular risk in systemic inflammatory diseases].
AB  - Systemic inflammatory diseases are associated with increased cardiovascular
      morbidity and mortality. The link between inflammatory and cardiovascular
      diseases can be attributed to the coexistence of classical risk factors and
      inflammatory mechanisms activated during systemic inflammatory diseases involving
      the immune system. Unfavorable metabolic effects of anti-inflammatory drugs can
      also contribute to increase cardiovascular risk. Yet, clinical implications of
      these findings are not entirely clear, and deeper knowledge and awareness of
      cardiac involvement in inflammatory diseases are necessary. The aim of this
      review is to summarize cardiac involvement in systemic inflammatory diseases and
      to identify aspects where evidence is currently lacking that would deserve
      further investigation in the future. 

PMID- 23877550
TI  - [Ischemic heart disease and depression: an underestimated clinical association].
AB  - Patients with acute or chronic ischemic heart disease have a high incidence of
      depression, and a variable proportion of patients (ranging from 14% to 47%)
      suffer from major or subclinical depression. In addition, chronic depression has
      been shown to be associated with the development or progression of coronary
      atherosclerosis. Besides a poor quality of life, depressive symptoms in patients
      with ischemic heart disease result in a poor prognosis, as cardiovascular event
      rates are 2-2.5 times higher than in their counterparts without depressive
      symptoms. A variety of pathogenetic mechanisms may play a role, including
      pathophysiological (dysfunction of the autonomic nervous system or hypothalamic
      pituitary-adrenal axis, platelet hyperaggregability, inflammation, endothelial
      dysfunction and genetic predisposition) and behavioral mechanisms (inadequate
      therapy adherence, obesity, smoking, sedentary lifestyle). However, in patients
      with ischemic heart disease, depression often goes undiagnosed or untreated.
      Several screening procedures including questionnaires for patients with heart
      disease, along with the help of a psychiatrist, may facilitate not only the
      diagnosis of depressive symptoms but also the pharmacological and/or
      physiotherapeutic management. The use of tricyclic antidepressant agents should
      be avoided in patients with heart disease, whereas selective serotonin reuptake
      inhibitors have been shown to be safe in this patient population. However, no
      evidence is available to support that use of these drugs is associated with a
      reduced risk of cardiovascular events at follow-up. Psychotherapy proved to be
      effective in reducing depressive symptoms but ineffective in improving prognosis.
      In this review, epidemiology and pathophysiology of depression in patients with
      ischemic heart disease are described, with a focus on stratification of
      depressive symptoms and potential therapeutic strategies. 

PMID- 23877551
TI  - [Aortic disease in Marfan syndrome: current role of surgery and thoracic
      endovascular aortic repair].
AB  - Aortic disease is the most life-threatening complication of Marfan syndrome. Over
      the last decades, improved medical management and surgical results of
      prophylactic aortic interventions on the aortic root have dramatically increased
      expectancy of life in Marfan syndrome patients. As a result, the number of Marfan
      syndrome patients requiring secondary interventions on the thoracic or thoraco
      abdominal aorta due to development of aortic disease or new type B dissection,
      has substantially increased. In this setting, open surgical interventions
      represent the treatment of choice. Nevertheless, the available literature,
      although restricted to small case series, indicates that endovascular repair is a
      feasible treatment option leading to satisfactory short-term results and may
      provide a bridging role to definitive open reconstruction. The aim of this paper
      was to review surgical and endovascular outcomes of aortic disease in Marfan
      syndrome. 

PMID- 23877552
TI  - [ The new 2010 Ghent criteria for the indication to surgical treatment of
      patients affected by Marfan syndrome. Experience of a single cardiac surgery
      center].
AB  - BACKGROUND: The diagnosis and surgical treatment of patients with Marfan syndrome
      remain controversial. It is of utmost importance to identify patients at risk for
      acute aortic events to establish the correct surgical timing and the appropriate
      surgical treatment. METHODS: From May 2008 to December 2012, 500 patients were
      screened at the Marfan Presidium of the Tor Vergata University Hospital of Rome
      (Italy). Patients were evaluated by a cardiac surgeon, including
      echocardiographic, orthopedic, ophthalmologic and dental examinations. All
      patients received genetic counseling, and genetic sampling was performed if
      appropriate. RESULTS: The diagnosis of Marfan syndrome was confirmed in 146
      patients (29.2%). Fifty-four patients (37%) underwent cardiac surgery on the
      aortic root, 4 patients had surgery on the mitral valve, 13 patients had combined
      surgery; 11 cases were emergent surgery for acute aortic dissection. Twenty-eight
      patients (52%) were operated on at our Division: 13 underwent valve-sparing
      aortic root replacement (David procedure), 1 underwent Yacoub remodeling
      procedure and 14 underwent Bentall procedure. Following the establishment of the
      Marfan Center, the David aortic valve-sparing operation was the most frequently
      performed procedure compared to the previous period of surgical activity (63 vs
      22%, p<0.0001). CONCLUSIONS: Regular follow-up twice a year may allow to identify
      patients at risk for acute aortic syndromes. Early surgical treatment is
      recommended in these patients to achieve optimal results of valve-sparing
      procedures and life-saving management, especially for patients who live far away
      from a cardiac surgery center.

PMID- 23877553
TI  - [Right heart failure in a patient with unexplained tricuspid regurgitation and a
      rare congenital heart disease].
AB  - We report the case of a 63-year-old woman admitted to the intensive care unit
      because of acute decompensated right heart failure. Transthoracic and
      transesophageal echocardiography revealed severe right ventricular dysfunction
      with severe tricuspid regurgitation of unknown origin and a large membrane
      running from the inferior vena cava to the interatrial septum with significant
      diastolic transmembrane gradient, consistent with the diagnosis of cor
      triatriatum dexter. The clinical interest of our findings relies on the
      coexistence of multiple diseases, which actually contributed in a different but
      synergistic manner to right heart failure. 

PMID- 23877555
TI  - "Nebs no more after 24": a pilot program to improve the use of appropriate
      respiratory therapies.

PMID- 23877556
TI  - Coronal limb alignment and indications for high tibial osteotomy in patients
      undergoing revision ACL reconstruction.
AB  - BACKGROUND: Failed ACL reconstruction frequently is accompanied by irreparable
      medial meniscal tear and/or visible osteoarthritis (OA) in the medial
      tibiofemoral joint. Thus, assessment for the presence of varus malalignment is
      important in caring for patients in whom revision ACL reconstruction is
      considered. QUESTIONS/PURPOSES: We determined whether patients undergoing
      revision ACL reconstruction (1) have more frequent varus malalignment coupled
      with more severe degrees of medial meniscal injury and/or medial tibiofemoral OA,
      and (2) would meet potential indications for high tibial osteotomy more
      frequently than patients undergoing primary ACL reconstruction. METHODS: We
      compared 58 patients undergoing revision ACL reconstruction and 116 patients
      undergoing primary ACL reconstruction. The mechanical tibiofemoral angle and the
      weight loading line (%) of the knee were measured. Additionally, radiographic
      degrees of OA in the tibiofemoral joints, and meniscal conditions were assessed.
      Then, proportions of potential candidates for high tibial osteotomy between the
      two groups were compared based on the following indications: (1) weight loading
      line less than 5%, (2) weight loading line less than 25% and medial tibiofemoral
      OA Kellgren-Lawrence Grade 3 or greater, or (3) weight loading line less than 25%
      and Kellgren-Lawrence Grade 2 medial tibiofemoral OA plus subtotal or total
      medial meniscectomy status. RESULTS: The revision ACL reconstruction group had
      more frequent varus malalignment in terms of proportion of knees with more varus
      mechanical tibiofemoral angle than varus 5 degrees  (19% versus 8%, p = 0.029)
      and knees with weight loading line less than 25% (22% versus 9%, p = 0.011). This
      group also had more frequent high-grade injury of the medial meniscus (34% versus
      16%, p = 0.007) and tended to have more frequent higher-grade radiographic OA at
      the medial tibiofemoral joint (19% versus 9%, p = 0.076). The percentage of
      patients meeting potential indications for high tibial osteotomy was greater in
      this group (14% versus 2%, p = 0.003). CONCLUSIONS: We found that many patients
      undergoing revision ACL surgery may be reasonable candidates for concurrent high
      tibial osteotomy to address concomitant alignment and OA issues in the medial
      compartment. However, whether that additional intervention is offset by added
      risk and morbidity should be the focus of a future study, as it cannot be
      answered by a study of this design.

PMID- 23877557
TI  - Cytoskeleton: Building actin networks on vesicles.

PMID- 23877565
TI  - Association of passive smoking with cognitive impairment in nonsmoking older
      adults: a systematic literature review and a new study of Chinese cohort.
AB  - Association of passive smoking with cognitive impairment in older adults is
      unclear. We carried out a systematic literature review and a new study to
      determine the association. There were 3 cross-sectional studies published,
      showing a significant association of passive smoking with cognitive impairment (a
      relative risk (RR) of about 1.30-1.90). In the new cohort study, we interviewed
      1081 never-smoking participants aged >= 65 years in China using a standard method
      of the Geriatric Mental State-Automated Geriatric Examination for Computer
      Assisted Taxonomy and found a significant association with dose response;
      multivariate adjusted RR was 1.02 (95% confidence interval 0.67-1.55) in > 0 to
      49 exposure level years of passive smoking, 1.57 (1.00-2.47) in 50 to 99, and
      2.12 (1.24-3.63) in >= 100, trend P = .008. The relationship seems not to be a
      reverse causality of the effect. Passive smoking could be considered an important
      risk factor for cognitive impairment in older adults. Avoiding exposure to
      passive smoking would help to preserve cognitive decline in later life.

PMID- 23877566
TI  - Tandem thia-Fries rearrangement--cyclisation of 2-(trimethylsilyl)phenyl
      trifluoromethanesulfonate benzyne precursors.
AB  - A novel transformation of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate
      aryne precursors is described. 

PMID- 23877564
TI  - Control of cell cycle transcription during G1 and S phases.
AB  - The accurate transition from G1 phase of the cell cycle to S phase is crucial for
      the control of eukaryotic cell proliferation, and its misregulation promotes
      oncogenesis. During G1 phase, growth-dependent cyclin-dependent kinase (CDK)
      activity promotes DNA replication and initiates G1-to-S phase transition. CDK
      activation initiates a positive feedback loop that further increases CDK
      activity, and this commits the cell to division by inducing genome-wide
      transcriptional changes. G1-S transcripts encode proteins that regulate
      downstream cell cycle events. Recent work is beginning to reveal the complex
      molecular mechanisms that control the temporal order of transcriptional
      activation and inactivation, determine distinct functional subgroups of genes and
      link cell cycle-dependent transcription to DNA replication stress in yeast and
      mammals. 

PMID- 23877567
TI  - Cardiac computed tomography and computed tomography angiography in the evaluation
      of patients prior to transcatheter aortic valve implantation.
AB  - PURPOSE OF REVIEW: Advancements in the use of multidetector computed tomography
      (CT) in transcatheter aortic valve implantation/transcatheter aortic valve
      replacement (TAVI/TAVR) over the last year reaffirm its role in the evaluation of
      preprocedural planning and procedural guidance. The purpose of this review is to
      provide an up-to-date review of recently published data, with a particular focus
      on annular sizing and transcatheter heart valve selection to help reduce
      paravalvular regurgitation. RECENT FINDINGS: Recent data have confirmed that
      multidetector computed tomography (MDCT) measures of the annulus are highly
      reproducible across multiple readers and workstation platforms. MDCT has also
      been shown to have a strong discriminatory ability to predict and reduce
      postprocedural paravalvular regurgitation (PAR), as well as presenting the
      current data for integrating CT measures of the annulus into sizing. SUMMARY:
      Over the last year, MDCT has solidified itself as an essential tool for the
      evaluation of the aortic root and annulus prior to TAVI. MDCT annular
      measurements are highly reproducible and now form the basis for transcatheter
      heart valve selection, with early data suggesting that CT integration can reduce
      paravalvular regurgitation.

PMID- 23877568
TI  - Dermatopontin regulates fibrin formation and its biological activity.
AB  - Dermatopontin (DP) is a small extracellular matrix component in the dermis.
      Fibrin is a major component of a provisional matrix that is formed just after
      wounding. Previously, we found that DP was present in the provisional matrix, and
      it interacted with fibrin. Here, we examined the role of DP on fibrin function.
      DP interacted with both the fibrin monomer and fibrils, and was incorporated into
      the fibrils during fibrin formation. A DP sequence, PHGQVVVAVRS, was identified
      as a fibrin-binding site, and a globular D domain of fibrin was the binding site
      for DP. DP accelerated fibrin fibril formation into structurally modified
      fibrils. Fibrin fibrils formed in the presence of DP enhanced both endothelial
      cell attachment and cell spreading. The attached cells developed a more organized
      cytoskeleton when compared with those that attached to fibrin fibrils only. The
      main receptor for cell adhesion was identified as alphavbeta3 integrin, and a
      cooperating receptor was a beta1-containing integrin species, probably
      alpha5beta1 integrin. These results indicate that DP can modify certain
      biological functions of fibrin, and thus a another function of this extracellular
      matrix protein was revealed. In addition, the fibrin-DP complex might become
      useful for developing an improved artificial matrix for improving wound healing. 

PMID- 23877569
TI  - Non-melanoma skin cancer incidence and impact of skin cancer screening on
      incidence.
AB  - Non-melanoma skin cancer (NMSC) is the most common malignancy, whose public
      health significance is often unrecognized. This analysis has two objectives:
      first, to provide up-to-date incidence estimates by sex, age group, histological
      type, and body site; and second, to study the impact of skin cancer screening.
      The impact of screening on NMSC incidence in Schleswig-Holstein, Germany, is
      analyzed by comparing four time periods of different screening settings (no
      screening (1998-2000), pilot project (Skin Cancer Research to Provide Evidence
      for Effectiveness of Screening in Northern Germany, SCREEN, 2003-2004), after
      SCREEN (2004-2008), and nation-wide skin cancer screening (2008-2010)) to a
      reference region (Saarland, Germany). Age-standardized (Europe) NMSC incidence
      was 119/100,000 for women and 145/100,000 for men in the most recent screening
      period in Schleswig-Holstein (2008-2010). During implementation of SCREEN (2003
      2004), incidence increased from 81.5/100,000 to 111.5/100,000 (1998-2000) by 47%
      for women and 34% for men. All age groups in women were affected by the increase,
      but increases for men were mostly limited to the older age groups. Incidence in
      Saarland first increased slowly, but increased steeply with the introduction of
      the nation-wide skin cancer screening in 2008 (+47% for women and +40% for men,
      reference 2004-2008). Observed changes are most likely attributed to screening
      activities. 

PMID- 23877570
TI  - Kynurenine increases matrix metalloproteinase-1 and -3 expression in cultured
      dermal fibroblasts and improves scarring in vivo.
AB  - We previously demonstrated that the formation of hypertrophic scarring on the
      wounds of a rabbit ear fibrotic model was significantly reduced by grafting a
      bilayer skin substitute expressing indoleamine 2,3-dioxygenase (IDO). Here, we
      hypothesize that the improved healing quality is due to extracellular matrix
      modulatory effect of IDO-mediated tryptophan metabolites. To test this
      hypothesis, a series of in vitro and in vivo experiments were conducted and the
      findings revealed a significant increase in the expression of matrix
      metalloproteinase 1 (MMP-1) in fibroblasts either transduced with human IDO gene
      or cultured with conditioned media obtained from IDO-expressing cells. Consistent
      with this finding, kynurenine (Kyn) treatment markedly increased the levels of
      MMP-1 and MMP-3 expression through activation of the MEK (mitogen-activated
      protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase)-ERK1/2
      MAPK signaling pathway. On the other hand, Kyn significantly suppressed the
      expression of type I collagen in fibroblasts as compared with that of control. To
      test the anti-fibrogenic effect of Kyn in an in vivo model, rabbit ear fibrotic
      wounds were topically treated with cream containing 50 MUg Kyn per l00 MUl of
      cream per wound. The result showed a marked improvement in scar formation
      relative to the controls. These findings collectively suggest that Kyn can
      potentially be used as an anti-fibrogenic agent for treating hypertrophic
      scarring. 

PMID- 23877572
TI  - Derivation of no-effect and reference-level sediment quality values for
      application at Saskatchewan uranium operations.
AB  - To date, the majority of empirical approaches used to derive sediment quality
      values (SQVs) have focused on metal concentrations in sediment associated with
      adverse effects on benthic invertebrate communities. Here, we propose the no
      effect (NE) approach. This SQV derivation methodology uses metal concentrations
      in sediment associated with unaffected benthic communities (i.e., from reference
      sites and lightly contaminated no-effect sites) and accounts for local benthic
      invertebrate tolerance and potential chemical interactions at no-effect exposure
      sites. This NE approach was used to propose alternative regional SQVs for uranium
      operations in northern Saskatchewan. Three different sets of NE values were
      derived using different combinations of benthic invertebrate community effects
      criteria (abundance, richness, evenness, Bray-Curtis index). Additionally,
      reference values were derived based solely on sediment metal concentrations from
      reference sites. In general, NE values derived using abundance, richness, and
      evenness (NE1 and NE2 values) were found to be higher than the NE values derived
      using all four metrics (NE3 values). Derived NE values for Cr, Cu, Pb, and V did
      not change with the incorporation of additional effects criteria due to a lack of
      influence from the uranium operations on the concentrations of these metals in
      sediment. However, a gradient of exposure concentrations was apparent for As, Mo,
      Ni, Se, and U in sediment which allowed for tolerable exposure levels of these
      metals in sediment to be defined. The findings from this assessment have
      suggested a range of new, alternate metal SQVs for use at uranium operations in
      northern Saskatchewan. 

PMID- 23877571
TI  - Antibiotics-related adverse events in the infectious diseases department of a
      French teaching hospital: a prospective study.
AB  - Antibiotics are a significant cause of adverse events (AE), but few studies have
      focused on prescriptions in hospitalized patients. In infectious diseases
      departments, the high frequency and diversity of antibiotics prescribed makes AE
      post-marketing monitoring easier. The aim of our study was to assess the
      incidence and type of AE in the infectious diseases department of a French
      teaching tertiary-care hospital. The main characteristics of each
      hospitalization, including all antibiotics prescribed and any significant AE were
      recorded prospectively in the medical dashboard of the department. We included
      all patients having suffered an AE due to systemic antibiotics between January
      2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an
      antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were
      gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16
      (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood
      disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading
      causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and
      38% were continued (including 11% with a dose modification). Patients suffering
      from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data
      could help choosing the safest antibiotic when several options are possible.

PMID- 23877573
TI  - The levels and composition of persistent organic pollutants in alluvial
      agriculture soils affected by flooding.
AB  - The concentrations and composition of persistent organic pollutants (POPs) were
      determined in alluvial soils subjected to heavy flooding in a rural region of
      Poland. Soil samples (n = 30) were collected from the upper soil layer from a 70
      km(2) area. Chemical determinations included basic physicochemical properties and
      the contents of polychlorinated biphenyls (PCBs), hexachlorocyclohexanes (HCHs),
      dichlorodiphenyltrichloroethanes (DDTs) and polycyclic aromatic hydrocarbons
      (PAHs, 16 compounds). The median concentrations of Sigma7PCB (PCB28 + PCB52 +
      PCB101 + PCB118 + PCB138 + PCB153 + PCB180), Sigma3HCH (alpha-HCH + beta-HCH +
      gamma-HCH) and Sigma3pp'(DDT + DDE + DDD) were 1.60 +/- 1.03, 0.22 +/- 0.13 and
      25.18 +/- 82.70 MUg kg(-1), respectively. The median concentrations of the most
      abundant PAHs, phenanthrene, fluoranthene, pyrene, benzo[b]fluoranthene and
      benzo[a]pyrene were 50 +/- 37, 38 +/- 27, 29 +/- 30, 45 +/- 36 and 24 +/- 22 MUg
      kg(-1), respectively. Compared with elsewhere in the world, the overall level of
      contamination with POPs was low and similar to the levels in agricultural soils
      from neighbouring countries, except for benzo[a]pyrene and DDT. There was no
      evidence that flooding affected the levels of POPs in the studied soils. The
      patterns observed for PAHs and PCBs indicate that atmospheric deposition is the
      most important long-term source of these contaminants. DDTs were the dominant
      organochlorine pesticides (up to 99%), and the contribution of the parent pp'
      isomer was up to 50 % of the SigmaDDT, which indicates the advantage of aged
      contamination. A high pp'DDE/pp'DDD ratio suggests the prevalence of aerobic
      transformations of parent DDT. Dominance of the gamma isomer in the HCHs implies
      historical use of lindane in the area. The effect of soil properties on the POP
      concentrations was rather weak, although statistically significant links with the
      content of the <0.02-mm fraction, Ctotal or Ntotal were observed for some
      individual compounds in the PCB group.

PMID- 23877574
TI  - Chemical constraints on new man-made lakes.
AB  - The formation of reservoirs often affects water quality strongly, with the
      changes in the physicochemical properties being ascribed to decomposition of
      remaining organic matter arising from leaching and (biological and chemical)
      breakdown processes. In this study, experiments under laboratory conditions were
      performed to show that the nature of the course particulate organic matter (CPOM;
      i.e., leaves, branches, barks, and litter) determines the decomposition kinetics
      in new reservoirs. Effects on the water quality can be of short-, mid-, and long
      term duration for all types of CPOM, as indicated in the mathematical modeling of
      the decomposition kinetics. Leaves and litter displayed the shortest half-life
      times (51 and 40 days, respectively) and the highest potential of
      leaching/oxidation of labile compounds (19 and 21%, respectively). On the other
      hand, decomposition of branches and barks generated the lowest oxygen consumption
      (74 and 44 mg oxygen/g dry mass (DM), respectively). During formation of the
      reservoir, the incorporation and decomposition of organic matter prevailed over
      material exportation. Therefore, in addition to a decrease in oxygen availability
      the concentration of biochemical oxygen demand (BOD) and nutrients increased.
      After the filling stage, there was significant loss of organic matter via
      oxidation, sedimentation, biological assimilation, and export, thus causing the
      BOD concentration and the fertility of the water to decrease.

PMID- 23877575
TI  - Uptake of arsenic by alkaline soils near alkaline coal fly ash disposal
      facilities.
AB  - The attenuation of arsenic in groundwater near alkaline coal fly ash disposal
      facilities was evaluated by determining the uptake of arsenic from ash leachates
      by surrounding alkaline soils. Ten different alkaline soils near a retired coal
      fly ash impoundment were used in this study with pH ranging from 7.6 to 9.0,
      while representative coal fly ash samples from two different locations in the
      coal fly ash impoundment were used to produce two alkaline ash leachates with pH
      7.4 and 8.2. The arsenic found in the ash leachates was present as arsenate
      [As(V)]. Adsorption isotherm experiments were carried out to determine the
      adsorption parameters required for predicting the uptake of arsenic from the ash
      leachates. For all soils and leachates, the adsorption of arsenic followed the
      Langmuir and Freundlich equations, indicative of the favorable adsorption of
      arsenic from leachates onto all soils. The uptake of arsenic was evaluated as a
      function of ash leachate characteristics and the soil components. The uptake of
      arsenic from alkaline ash leachates, which occurred mainly as calcium hydrogen
      arsenate, increased with increasing clay fraction of soil and with increasing
      soil organic matter of the alkaline soils. Appreciable uptake of arsenic from
      alkaline ash leachates with different pH and arsenic concentration was observed
      for the alkaline soils, thus attenuating the contamination of groundwater
      downstream of the retired coal fly ash impoundment.

PMID- 23877577
TI  - Assessing changes in the Presque Isle Bay watershed fish community using a
      modified index of biotic integrity: before and after the elimination of combined
      sewer overflows.
AB  - An index of biotic integrity and species richness were used to assess changes in
      the Presque Isle Bay watershed fish community before and after the elimination of
      combined sewer overflows (CSOs). The fish community was sampled with a backpack
      electrofisher in 2011 at 12 stream locations on 4 tributaries of Presque Isle
      Bay, Erie County, Pennsylvania. All sites were previously sampled in 2001.
      Significant increases in species richness and index of biotic integrity (IBI)
      scores were observed in 2011 compared to 2001. The significant increases in
      species richness and IBI scores occurred following the elimination of 10 CSOs to
      Garrison Run, 7 CSOs to Cascade Creek, and 37 CSOs to Mill Creek. Despite the
      increased richness and IBI scores, the fish community remains in poor condition,
      which may be related to the highly urbanized land use of the watershed. Urban
      land uses comprise 77% of the Presque Isle Bay watershed, and in both 2011 and
      2001, the watershed as a whole did not meet warm-water habitat criteria. It is
      unlikely that the fish community will continue to recover without addressing
      urbanization throughout the watershed.

PMID- 23877576
TI  - Noninvasive heavy metal pollution assessment by means of Iberian wolf (Canis
      lupus signatus) hair from Galicia (NW Spain): a comparison with invasive samples.
AB  - The current study represents the first investigation of the suitability of wolf
      hair as indicator tissue for metal exposure and accumulation within NW Spanish
      ecosystems. Dead animals, which were not specifically killed for these purposes,
      were necropsied, and further toxicological analyses were performed in order to
      establish the heavy metal content (Pb, Cd, and Zn) in liver, kidney, and hair, by
      means of inductively coupled plasma optical emission spectrometry. Two different
      factors, gender and age, were considered in order to determine their influence on
      heavy metal accumulation. Mean liver, kidney and hair concentrations of both
      toxic element, Cd (0.528, 2.692, and 0.026 ppm) and Pb (4.108, 0.031, and 0.196
      ppm) considered on a dry weight basis, were situated below the established as
      acute toxicity levels for mammals. The highest concentrations were quantified for
      Zn, with means ranging from a maximum in hair samples (150.9 ppm) to a minimum in
      kidney samples (25.81 ppm). When the variable of gender and age were considered,
      female and adult wolves had higher concentrations of Cd in all the considered
      organs, although differences were only statistically significant for kidney.
      Neither the sex nor the age had a significant effect on Pb and Zn concentrations.
      A significant positive correlation (p < 0.05) was identified between hair and
      liver Pb concentrations, as well as between hair and kidney Cd concentrations,
      thus suggesting the interest of the noninvasive sample for future
      ecotoxicological biomonitoring studies.

PMID- 23877578
TI  - Pooled analysis of case-control studies on acoustic neuroma diagnosed 1997-2003
      and 2007-2009 and use of mobile and cordless phones.
AB  - We previously conducted a case-control study of acoustic neuroma. Subjects of
      both genders aged 20-80 years, diagnosed during 1997-2003 in parts of Sweden,
      were included, and the results were published. We have since made a further study
      for the time period 2007-2009 including both men and women aged 18-75 years
      selected from throughout the country. These new results for acoustic neuroma have
      not been published to date. Similar methods were used for both study periods. In
      each, one population-based control, matched on gender and age (within five
      years), was identified from the Swedish Population Registry. Exposures were
      assessed by a self-administered questionnaire supplemented by a phone interview.
      Since the number of acoustic neuroma cases in the new study was low we now
      present pooled results from both study periods based on 316 participating cases
      and 3,530 controls. Unconditional logistic regression analysis was performed,
      adjusting for age, gender, year of diagnosis and socio-economic index (SEI). Use
      of mobile phones of the analogue type gave odds ratio (OR) = 2.9, 95% confidence
      interval (CI) = 2.0-4.3, increasing with >20 years latency (time since first
      exposure) to OR = 7.7, 95% CI = 2.8-21. Digital 2G mobile phone use gave OR =
      1.5, 95% CI = 1.1-2.1, increasing with latency >15 years to an OR = 1.8, 95% CI =
      0.8-4.2. The results for cordless phone use were OR = 1.5, 95% CI = 1.1-2.1, and,
      for latency of >20 years, OR = 6.5, 95% CI = 1.7-26. Digital type wireless phones
      (2G and 3G mobile phones and cordless phones) gave OR = 1.5, 95% CI = 1.1-2.0
      increasing to OR = 8.1, 95% CI = 2.0-32 with latency >20 years. For total
      wireless phone use, the highest risk was calculated for the longest latency time
      >20 years: OR = 4.4, 95% CI = 2.2-9.0. Several of the calculations in the long
      latency category were based on low numbers of exposed cases. Ipsilateral use
      resulted in a higher risk than contralateral for both mobile and cordless phones.
      OR increased per 100 h cumulative use and per year of latency for mobile phones
      and cordless phones, though the increase was not statistically significant for
      cordless phones. The percentage tumour volume increased per year of latency and
      per 100 h of cumulative use, statistically significant for analogue phones. This
      study confirmed previous results demonstrating an association between mobile and
      cordless phone use and acoustic neuroma.

PMID- 23877579
TI  - Suitability of customer relationship management systems for the management of
      study participants in biomedical research.
AB  - BACKGROUND: Longitudinal biomedical research projects study patients or
      participants over a course of time. No IT solution is known that can manage study
      participants, enhance quality of data, support re-contacting of participants,
      plan study visits, and keep track of informed consent procedures and recruitments
      that may be subject to change over time. In business settings management of
      personal is one of the major aspects of customer relationship management systems
      (CRMS). OBJECTIVES: To evaluate whether CRMS are suitable IT solutions for study
      participant management in biomedical research. METHODS: Three boards of experts
      in the field of biomedical research were consulted to get an insight into recent
      IT developments regarding study participant management systems (SPMS).
      Subsequently, a requirements analysis was performed with stakeholders of a major
      biomedical research project. The successive suitability evaluation was based on
      the comparison of the identified requirements with the features of six CRMS.
      RESULTS: Independently of each other, the interviewed expert boards confirmed
      that there is no generic IT solution for the management of participants. Sixty
      four requirements were identified and prioritized in a requirements analysis. The
      best CRMS was able to fulfill forty-two of these requirements. The non-fulfilled
      requirements demand an adaption of the CRMS, consuming time and resources,
      reducing the update compatibility, the system's suitability, and the security of
      the CRMS. CONCLUSIONS: A specific solution for the SPMS is favored instead of a
      generic and commercially-oriented CRMS. Therefore, the development of a small and
      specific SPMS solution was commenced and is currently on the way to completion.

PMID- 23877580
TI  - Progress in bioleaching: part B: applications of microbial processes by the
      minerals industries.
AB  - This review presents developments and applications in bioleaching and mineral
      biooxidation since publication of a previous mini review in 2003 (Olson et al.
      Appl Microbiol Biotechnol 63:249-257, 2003). There have been discoveries of newly
      identified acidophilic microorganisms that have unique characteristics for
      effective bioleaching of sulfidic ores and concentrates. Progress has been made
      in understanding and developing bioleaching of copper from primary copper sulfide
      minerals, chalcopyrite, covellite, and enargite. These developments point to low
      oxidation-reduction potential in concert with thermophilic bacteria and archaea
      as a potential key to the leaching of these minerals. On the commercial front,
      heap bioleaching of nickel has been commissioned, and the mineral biooxidation
      pretreatment of sulfidic-refractory gold concentrates is increasingly used on a
      global scale to enhance precious metal recovery. New and larger stirred-tank
      reactors have been constructed since the 2003 review article. One biooxidation
      heap process for pretreatment of sulfidic-refractory gold ores was also
      commercialized. A novel reductive approach to bioleaching nickel laterite
      minerals has been proposed. 

PMID- 23877581
TI  - Molecular diversity and tools for deciphering the methanogen community structure
      and diversity in freshwater sediments.
AB  - Methanogenic archaeal communities existing in freshwater sediments are
      responsible for approximately 50 % of the total global emission of methane. This
      process contributes significantly to global warming and, hence, necessitates
      interventional control measures to limit its emission. Unfortunately, the
      diversity and functional interactions of methanogenic populations occurring in
      these habitats are yet to be fully characterized. Considering several
      disadvantages of conventional culture-based methodologies, in recent years,
      impetus is given to molecular biology approaches to determine the community
      structure of freshwater sedimentary methanogenic archaea. 16S rRNA and methyl
      coenzyme M reductase (mcrA) gene-based cloning techniques are the first choice
      for this purpose. In addition, electrophoresis-based (denaturing gradient gel
      electrophoresis, temperature gradient gel electrophoresis, and terminal
      restriction fragment length polymorphism) and quantitative real-time polymerase
      chain reaction techniques have also found extensive applications. These
      techniques are highly sensitive, rapid, and reliable as compared to traditional
      culture-dependent approaches. Molecular diversity studies revealed the dominance
      of the orders Methanomicrobiales and Methanosarcinales of methanogens in
      freshwater sediments. The present review discusses in detail the status of the
      diversity of methanogens and the molecular approaches applied in this area of
      research. 

PMID- 23877583
TI  - Assessing nanoparticle toxicity in cell-based assays: influence of cell culture
      parameters and optimized models for bridging the in vitro-in vivo gap.
AB  - The number of newly engineered nanomaterials is vastly increasing along with
      their applications. Despite the fact that there is a lot of interest and effort
      is being put into the development of nano-based biomedical applications, the
      level of translational clinical output remains limited due to uncertainty in the
      toxicological profiles of the nanoparticles (NPs). As NPs used in biomedicines
      are likely to directly interact with cells and biomolecules, it is imperative to
      rule out any adverse effect before they can be safely applied. The initial
      screening for nanotoxicity is preferably performed in vitro, but extrapolation to
      the in vivo outcome remains very challenging. In addition, generated in vitro and
      in vivo data are often conflicting, which consolidates the in vitro-in vivo gap
      and impedes the formulation of unambiguous conclusions on NP toxicity.
      Consequently, more consistent and relevant in vitro and in vivo data need to be
      acquired in order to bridge this gap. This is in turn in conflict with the
      efforts to reduce the number of animals used for in vivo toxicity testing.
      Therefore the need for more reliable in vitro models with a higher predictive
      power, mimicking the in vivo environment more closely, becomes more prominent. In
      this review we will discuss the current paradigm and routine methods for
      nanotoxicity evaluation, and give an overview of adjustments that can be made to
      the cultivation systems in order to optimise current in vitro models. We will
      also describe various novel model systems and highlight future prospects. 

PMID- 23877582
TI  - Asymmetry of automatic change detection shown by the visual mismatch negativity:
      an additional feature is identified faster than missing features.
AB  - In two experiments, we demonstrated that an asymmetric effect of the brain
      electric activity that is elicited by nonattended visual stimuli is similar to
      the one found in responses observed in the performance of visual search tasks.
      The automatic detection of violated sequential regularities was investigated by
      measuring the visual mismatch negativity (vMMN) component of event-related brain
      potentials (ERPs). In Experiment 1, within a sequence of stimulus displays with O
      characters, infrequently presented Q characters elicited an earlier vMMN than did
      infrequent O characters within a sequence of Q characters. In Experiment 2,
      similar asymmetric results emerged if only 16% of the characters were different
      within an infrequent display. In both experiments, these stimuli were irrelevant;
      during the stimulus sequences, participants performed a demanding videogame. We
      suggest that the underlying match/mismatch and decision processes are similar in
      the vMMN and in the attention-related visual search paradigm, at least in the
      case of the stimuli in the present experiments.

PMID- 23877584
TI  - A comparison of physical abilities and match performance characteristics among
      elite and subelite under-14 soccer players.
AB  - This study aimed to identify characteristics of match performance and physical
      ability that discriminate between elite and subelite under-14 soccer players.
      Players were assessed for closed performance and movement, physiological
      responses, and technical actions during matches. Elite players covered more total
      m.min-1 (115.7 +/- 6.6 cf. 105.4 +/- 7.7 m.min-1) and high-intensity m.min-1
      (elite = 14.5 +/- 2.3 cf. 11.5 +/- 3.7 m.min-1) compared with subelite players.
      Elite players also attempted more successful (0.41 +/- 0.11 cf. 0.18 +/- 0.02)
      and unsuccessful ball retentions.min-1 (0.14 +/- 0.04 cf. 0.06 +/- 0.02) compared
      with subelite players. Elite players were faster over 10 m (1.9 +/- 0.1 cf. 2.3
      +/- 0.2 s) and faster dribblers (16.4 +/- 1.4 cf. 18.2 +/- 1.1 s) compared with
      subelite players. Speed (10 m) and successful ball retention.min-1 contributed to
      a predictive model, explaining 96.8% of the between-group variance. The analysis
      of match performance provides a more thorough understanding of the factors
      underlying talent among youth soccer players. 

PMID- 23877586
TI  - Lipase-catalyzed acidolysis of palm mid fraction oil with palmitic and stearic
      Fatty Acid mixture for production of cocoa butter equivalent.
AB  - Cocoa butter equivalent (CBE) was prepared by enzymatic acidolysis reaction of
      substrate consisting of refined palm mid fraction oil and palmitic-stearic fatty
      acid mixture. The reactions were performed in a batch reactor at a temperature of
      60  degrees C in an orbital shaker operated at 160 RPM. Different mass ratios of
      substrates were explored, and the composition of the five major triacylglycerols
      (TAGs) of the structured lipids was identified and quantified using cocoa butter
      certified reference material IRMM-801. The reaction resulted in production of
      cocoa butter equivalent with the TAGs' composition (1,3-dipalmitoyl-2-oleoyl
      glycerol 30.7%, 1-palmitoyl-2-oleoyl-3-stearoyl-rac-glycerol 40.1%, 1-palmitoy
      2,3- dioleoyl glycerol 9.0%, 1,3-distearoyl-2-oleoyl-glycerol 14.5 %, and 1
      stearoyl-2,3-dioleoyl glycerol 5.7%) and with onset melting temperature of 31.6 
      degrees C and peak temperature of 40.4  degrees C which are close to those of
      cocoa butter. The proposed kinetics model for the acidolysis reaction presented
      the experimental data very well. The results of this research showed that palm
      mid fraction oil TAGs could be restructured to produce value added product such
      as CBE.

PMID- 23877585
TI  - Difference in method of administration did not significantly impact item
      response: an IRT-based analysis from the Patient-Reported Outcomes Measurement
      Information System (PROMIS) initiative.
AB  - PURPOSE: To test the impact of method of administration (MOA) on the measurement
      characteristics of items developed in the Patient-Reported Outcomes Measurement
      Information System (PROMIS). METHODS: Two non-overlapping parallel 8-item forms
      from each of three PROMIS domains (physical function, fatigue, and depression)
      were completed by 923 adults (age 18-89) with chronic obstructive pulmonary
      disease, depression, or rheumatoid arthritis. In a randomized cross-over design,
      subjects answered one form by interactive voice response (IVR) technology, paper
      questionnaire (PQ), personal digital assistant (PDA), or personal computer (PC)
      on the Internet, and a second form by PC, in the same administration. Structural
      invariance, equivalence of item responses, and measurement precision were
      evaluated using confirmatory factor analysis and item response theory methods.
      RESULTS: Multigroup confirmatory factor analysis supported equivalence of factor
      structure across MOA. Analyses by item response theory found no differences in
      item location parameters and strongly supported the equivalence of scores across
      MOA. CONCLUSIONS: We found no statistically or clinically significant differences
      in score levels in IVR, PQ, or PDA administration as compared to PC. Availability
      of large item response theory-calibrated PROMIS item banks allowed for
      innovations in study design and analysis.

PMID- 23877587
TI  - Nephrology in china.
AB  - China has a large population and a high prevalence of chronic kidney disease
      (CKD). The increasing incidence of obesity and type 2 diabetes mellitus, coupled
      with an ageing population, will exacerbate the burden of CKD unless effective
      control and prevention strategies are implemented. The unmet challenges of
      managing the growing number of patients with end-stage renal disease (ESRD) in
      China are reflected by the lower rate of patients receiving dialysis relative to
      many Western countries, owing to a lack of financial and clinical resources, and
      inequalities in access to health care across regions and populations. The
      feasibility of expanding peritoneal dialysis is being examined, and ongoing
      health-care reforms provide an invaluable opportunity to improve the status and
      quality of dialysis for patients with ESRD in China. The Chinese Society of
      Nephrology (CSN) advocates for efforts focused on preventing CKD coupled with
      early detection, treatment, and adequate follow-up to reduce mortality and the
      long-term burden of CKD. In addition, rapid advances in nephrology research, from
      basic science to clinical epidemiology, as well as broad communication and
      collaboration between the CSN and other international nephrology societies, will
      promote the development of nephrology in China. 

PMID- 23877589
TI  - Acute coronary syndromes: management of acute coronary syndrome-renal outcomes.

PMID- 23877590
TI  - Fibrosis: the source of myofibroblasts in kidney fibrosis.

PMID- 23877588
TI  - FGF-23 and secondary hyperparathyroidism in chronic kidney disease.
AB  - The metabolic changes that occur in patients with chronic kidney disease (CKD)
      have a profound influence on mineral and bone metabolism. CKD results in altered
      levels of serum phosphate, vitamin D, calcium, parathyroid hormone (PTH) and
      fibroblast growth factor 23 (FGF-23); the increased levels of serum phosphate,
      PTH and FGF-23 contribute to the increased cardiovascular mortality in affected
      patients. FGF-23 is produced by osteocytes and osteoblasts and acts
      physiologically in the kidney to induce phosphaturia and inhibit the synthesis of
      1,25-dihydroxyvitamin D3. PTH acts directly on osteocytes to increase FGF-23
      expression. In addition, the high levels of PTH associated with CKD contribute to
      changes in bone remodelling that result in decreased levels of dentin matrix
      protein 1 and the release of low-molecular-weight fibroblast growth factors from
      the bone matrix, which stimulate FGF-23 transcription. A prolonged oral
      phosphorus load increases FGF-23 expression by a mechanism that includes local
      changes in the ratio of inorganic phosphate to pyrophosphate in bone. Other
      factors such as dietary vitamin D compounds, calcium, and metabolic acidosis all
      increase FGF-23 levels. This Review discusses the mechanisms by which secondary
      hyperparathyroidism associated with CKD stimulates bone cells to overexpress FGF
      23 levels. 

PMID- 23877598
TI  - Science imitates life.

PMID- 23877591
TI  - Echocardiographic screening of the general population and long-term survival: a
      randomized clinical study.
AB  - IMPORTANCE: Identification of structural heart disease in asymptomatic
      individuals could allow early disease-modifying treatment. OBJECTIVE: To examine
      whether echocardiographic screening in the general population improves long-term
      survival or reduces the risk of cardiovascular disease. DESIGN, SETTING, AND
      PARTICIPANTS: We studied 6861 middle-aged participants from the population-based
      Tromso Study in Norway. INTERVENTION: Participants were randomly allocated to an
      echocardiographic screening group (n = 3272) or a control group (n = 3589). MAIN
      OUTCOMES AND MEASURES: Using the as-treated approach, the data were analyzed for
      mortality and incidence of fatal and nonfatal myocardial infarction and stroke.
      RESULTS: During 15 follow-up years, 880 persons (26.9%) in the screening group
      and 989 persons (27.6%) in the control group died (hazard ratio, 0.97; 95% CI,
      0.89-1.06). No significant differences between the groups were observed in the
      secondary outcome measures (sudden death, mortality from any heart disease, or
      incidence of fatal and nonfatal myocardial infarction and stroke). CONCLUSIONS
      AND RELEVANCE: Echocardiographic screening for structural and valvular heart
      disease in the general population provided no benefit for mortality or for the
      risk of myocardial infarction or stroke.

PMID- 23877600
TI  - 2013 Tribranch Symposium. 3-5 June 2013. Safety: make it first, make it last.

PMID- 23877601
TI  - Catching up with cotton-top tamarins.

PMID- 23877602
TI  - Close the loop.

PMID- 23877603
TI  - Managing a group of qualified veterinary technicians.

PMID- 23877604
TI  - Document IACUC review.

PMID- 23877605
TI  - A word from USDA.

PMID- 23877606
TI  - One extra step.

PMID- 23877608
TI  - Urinary abnormalities in a mini rex rabbit (Oryctolagus cuniculus).

PMID- 23877609
TI  - Using anesthetics and analgesics in experimental traumatic brain injury.
AB  - Valid modeling of traumatic brain injury (TBI) requires accurate replication of
      both the mechanical forces that cause the primary injury and the conditions that
      lead to secondary injuries observed in human patients. The use of animals in TBI
      research is justified by the lack of in vitro or computer models that can
      sufficiently replicate the complex pathological processes involved. Measures to
      reduce nociception and distress must be implemented, but the administration of
      anesthetics and analgesics can influence TBI outcomes, threatening the validity
      of the research. In this review, the authors present evidence for the
      interference of anesthetics and analgesics in the natural course of brain injury
      in animal models of TBI. They suggest that drugs should be selected for or
      excluded from experimental TBI protocols on the basis of IACUC-approved
      experimental objectives in order to protect animal welfare and preserve the
      validity of TBI models. 

PMID- 23877610
TI  - Expression and treatment of pain-related behavioral depression.
AB  - Pain is often associated with clinically relevant depression of behavior and
      mood, and relief of pain-related depression is a common goal of treatment in both
      human and veterinary medicine. In the development of pharmacological compounds to
      treat pain and related depression, preclinical studies may be used to evaluate
      the analgesic potential of new drugs. Such studies require reliable, accurate
      assays of pain-related behavioral depression in animals. Intracranial self
      stimulation (ICSS) is a type of operant conditioning procedure that produces
      stable baseline behavioral response rates. The author reviews recent research on
      the use of ICSS to evaluate the expression and pharmacological modulation of pain
      related behavioral depression in rats. Results suggest that assays of pain
      depressed behavior using ICSS may serve as a useful new tool to improve the
      translation of preclinical findings to clinical results in analgesic drug
      development. 

PMID- 23877611
TI  - 'Sweatless' inspections: qualifications and proof.

PMID- 23877612
TI  - And that's the way it is. Global buzz--not press releases--generates earned media
      coverage.

PMID- 23877613
TI  - A part of something bigger.
AB  - Mr. Shannon talks about his job as a husbandry supervisor and his passion for
      playing a role in the advancement of science.

PMID- 23877614
TI  - Cognitive control in number magnitude processing: evidence from eye-tracking.
AB  - The unit-decade compatibility effect describes longer response times and higher
      error rates for incompatible (e.g., 37_52) than compatible (e.g., 42_57) number
      comparisons. Recent research indicated that the effect depends on the percentage
      of same-decade filler items. In the present study, we further examined this
      relationship by recording participants' eye-fixation behaviour. In four
      conditions, participants had to compare item sets with different filler item
      types (i.e., same-decade and same-unit filler items) and different numbers of
      same-decade filler items (i.e., 25, 50, and 75%). We found a weaker unit-decade
      compatibility effect with most fixations on tens in the condition with same-unit
      filler items. Moreover, the compatibility effect increased with the percentage of
      same-decade filler items which was accompanied by less fixations on tens and more
      fixations on units. Thus, our study provides first eye-tracking evidence for the
      influence of cognitive control in number processing.

PMID- 23877615
TI  - Anti-inflammatory and antioxidative effects of a methanol extract from bulbs of
      Scilla scilloides.
AB  - The extract from bulbs of Scilla scilloides exhibited inhibitory effects in
      lipoxygenase and hyaluronidase assays and various oxidation models in vitro.
      Incubating the cells in the presence of this extract ameliorated t-butyl
      hydroperoxide-induced cytotoxicity from 27% to 57% in a macrophage model. The
      results may indicate the potential role of S. scilloides for its anti
      inflammatory and antioxidative effects. 

PMID- 23877616
TI  - The vagotomy alleviates the anorectic effect of an excess amount of dietary
      leucine on rats fed a low-protein diet.
AB  - It is well known that large dose of leucine reduces the food intake and causes
      growth retardation in experimental animals when leucine is given with a low
      protein diet. However, the mechanism for the anorectic effect of leucine has not
      yet been clarified. We demonstrate here that the anorectic effect of leucine was
      significantly reduced in a vagotomized rat. 

PMID- 23877617
TI  - Location tests for biomarker studies: a comparison using simulations for the two
      sample case.
AB  - BACKGROUND: Gene, protein, or metabolite expression levels are often non-normally
      distributed, heavy tailed and contain outliers. Standard statistical approaches
      may fail as location tests in this situation. OBJECTIVES: In three Monte-Carlo
      simulation studies, we aimed at comparing the type I error levels and empirical
      power of standard location tests and three adaptive tests [O'Gorman, Can J Stat
      1997; 25: 269 -279; Keselman et al., Brit J Math Stat Psychol 2007; 60: 267- 293;
      Szymczak et al., Stat Med 2013; 32: 524 - 537] for a wide range of distributions.
      METHODS: We simulated two-sample scenarios using the g-and-k-distribution family
      to systematically vary tail length and skewness with identical and varying
      variability between groups. RESULTS: All tests kept the type I error level when
      groups did not vary in their variability. The standard non-parametric U-test
      performed well in all simulated scenarios. It was outperformed by the two non
      parametric adaptive methods in case of heavy tails or large skewness. Most tests
      did not keep the type I error level for skewed data in the case of heterogeneous
      variances. CONCLUSIONS: The standard U-test was a powerful and robust location
      test for most of the simulated scenarios except for very heavy tailed or heavy
      skewed data, and it is thus to be recommended except for these cases. The non
      parametric adaptive tests were powerful for both normal and non-normal
      distributions under sample variance homogeneity. But when sample variances
      differed, they did not keep the type I error level. The parametric adaptive test
      lacks power for skewed and heavy tailed distributions.

PMID- 23877618
TI  - DNA methylation is crucial for the early development in the Oyster C. gigas.
AB  - In vertebrates, epigenetic modifications influence gene transcription, and an
      appropriate DNA methylation is critical in development. Indeed, a precise
      temporal and spatial pattern of early gene expression is mandatory for a normal
      embryogenesis. However, such a regulation and its underlying mechanisms remain
      poorly understood in more distant organisms such as Lophotrochozoa. Thus, despite
      DNA in the oyster genome being methylated, the role of DNA methylation in
      development is unknown. To clarify this point, oyster genomic DNA was examined
      during early embryogenesis and found differentially methylated. Reverse
      transcriptase quantitative polymerase chain reaction indicated stage-specific
      levels of transcripts encoding DNA-methyltransferase (DNMT) and methyl-binding
      domain proteins. In addition, as highlighted by electronic microscopy and
      immunohistochemistry, the DNMT inhibitor 5-aza-cytidine induced alterations in
      the quantity and the localisation of methylated DNA and severe dose-dependent
      development alterations and was lethal after zygotic genome reinitiation.
      Furthermore, methyl-DNA-immunoprecipitation-quantitative polymerase chain
      reaction revealed that the transcription level of most of the homeobox gene
      orthologues examined, but not of the other early genes investigated, was
      inversely correlated with their specific DNA methylation. Altogether, our results
      demonstrate that DNA methylation influences gene expression in Crassostrea gigas
      and is critical for oyster development, possibly by specifically controlling the
      transcription level of homeobox orthologues. These findings provide evidence for
      the importance of epigenetic regulation of development in Lophotrochozoans and
      bring new insights into the early life of C. gigas, one of the most important
      aquaculture resources worldwide. 

PMID- 23877619
TI  - Identification and characterization of microRNAs in pearl oyster Pinctada
      martensii by Solexa deep sequencing.
AB  - MicroRNAs (miRNAs) are short-nucleotide RNA molecules that function as negative
      regulators of gene expression in various organisms. However, miRNAs of Pinctada
      martensii have not been reported yet. P. martensii is one of the main species
      cultured for marine pearl production in China and Japan. In order to obtain the
      repertoire of miRNAs in P. martensii, we constructed and sequenced small RNA
      libraries prepared from P. martensii by Solexa deep sequencing technology and got
      a total of 27,479,838 reads representing 3,176,630 distinct sequences. After
      removing tRNAs, rRNAs, snRNAs, and snoRNAs, 10,596,306 miRNA reads representing
      18,050 distinct miRNA reads were obtained. Based on sequence similarity and
      hairpin structure prediction, 258 P. martensii miRNAs (pm-miRNA) were identified.
      Among these pm-miRNAs, 205 were conserved across the species, whereas 53 were
      specific for P. martensii. The 3' end sequence of U6 snRNA was obtained from P.
      martensii by 3' rapid amplification of cDNA end PCR reaction and sequence
      directed cloning. Eight conserved pm-miRNAs and two novel pm-miRNAs were
      validated by stem-loop quantitative real-time PCR with U6 snRNA as an internal
      reference gene. pm-miRNAs and the reported biomineralization-related genes were
      subjected to target analysis by using target prediction tools. Some of the pm
      miRNAs, such as miR-2305 and miR-0046, were predicted to participate in
      biomineralization by regulating the biomineralization-related genes. Thus, this
      study demonstrated a large-scale characterization of pm-miRNAs and their
      potential function in biomineralization, providing a foundation to understand
      shell formation. 

PMID- 23877620
TI  - Crosstalk between p38 and Smad3 through TGF-beta1 in JEG-3 choriocarcinoma cells.
AB  - Choriocarcinoma is a highly malignant trophoblastic tumor related to pregnancy
      that often occurs with a complete hydatidiform mole. It grows quickly and can
      also widely metastasize to other organs or tissues through both the venous and
      lymphatic systems. The transforming growth factor-beta1 (TGF-beta1) belongs to a
      growth factor superfamily and has been suggested to play a critical role in
      regulating the genesis and development of choriocarcinoma through a variety of
      Smad-independent pathways, including the p38 MAPK pathway. Previous studies
      indicated that TGF-beta can activate the p38 MAPK pathway. In this study, we
      investigated Smad and p38 MAPK signaling in JEG-3 choriocarcinoma cells using p38
      MAPK inhibitor and TGF-beta receptor inhibitor. Immunofluorescence and western
      blot assays were used to detect the proteins in Smad and p38 MAPK pathways. Our
      data demonstrated that TGF-beta can activate Smad3 and induce Smad3 translocation
      into the nucleus in JEG-3 cells. Blockade of the TGF-beta pathway significantly
      reduced the expression levels of p38 and phospho-p38. p38 MAPK inhibitors (SB
      203580) can attenuate TGF-beta1-induced Smad3 expression and suppress the
      activation of smad3. These findings indicate crosstalk between p38 and smad3
      through TGF-beta1 in choriocarcinoma cells. 

PMID- 23877621
TI  - Cluster randomized controlled trial of a simple warfarin maintenance dosing
      algorithm versus usual care among primary care practices.
AB  - Many patients using warfarin are being managed in primary care and typically
      achieve a lower time in therapeutic range (TTR) for the international normalized
      ratio (INR) than patients in specialized care. A simple warfarin maintenance
      dosing tool could assist primary care physicians with improving TTR. We tested
      whether a simple warfarin maintenance dosing algorithm can improve TTR compared
      with usual care among Canadian primary care physicians. Primary care practices
      managing warfarin therapy without an anticoagulation clinic, computer decision
      support system or patient self-management tools enrolled 10-30 patients with
      target INR range 2-3. Practices were randomized to manage warfarin maintenance
      with the algorithm, or as usual in 2009-2010. Primary outcome was the mean
      individual patient TTR, and was compared between groups with adjustment for
      clustering within practices. There were 13 practices randomized to the Algorithm
      and 15 practices to Control, enrolling 240 and 297 patients respectively, with a
      mean follow-up of 280 days. Mean (standard deviation; SD) TTR before the study
      was comparable between groups [68 % (SD 26) for usual care vs. 70 % (SD 27) for
      the algorithm; p = 0.49]. Dosing decisions during the study in the algorithm
      group were more often in agreement with the algorithm's recommendations than with
      usual care (81 vs. 91 %; p < 0.0001). Mean study TTR of the algorithm group was
      not superior to usual care: [72.1 (SE 1.7) vs. 71.4 % (SE 1.5) respectively; p =
      0.73]. The simple warfarin maintenance dosing algorithm did not improve TTR
      compared with usual care among Canadian primary care practices. 

PMID- 23877622
TI  - Evaluation of the effects induced by dietary diphenyl diselenide on common carp
      Cyprinus carpio.
AB  - Several diets employed in aquaculture are enriched with selenium (Se), as it is a
      fundamental element to aquatic vertebrates. Diphenyl diselenide [(PhSe)2], which
      is a synthetic organoselenium compound, has been considered a potential
      antioxidant agent in different experimental models. Thus, the aim of this study
      was to evaluate the effects of dietary diphenyl diselenide at concentrations of
      1.5, 3.0, and 5.0 mg/kg for 60 days and to determine its optimal supplemental
      level for carp, Cyprinus carpio. Neither growth retardation nor hepatoxicity was
      induced by the inclusion of diphenyl diselenide at concentrations ranging from
      1.5 to 5.0 mg/kg. In addition, the inclusion of 3.0 mg/kg of diphenyl diselenide
      stimulated the weight and length of the carp. The supplementation with 1.5 and
      3.0 mg/kg of diphenyl diselenide did not produce oxidative damage in the tissues,
      verified by peroxidation lipid and protein carbonyl assays. However, at 5.0
      mg/kg, it caused an increase of the lipid peroxidation in the liver, brain, and
      muscle, and inhibited the cerebral acetylcholinesterase activity. An increase of
      the hepatic superoxide dismutase activity and non-protein thiols content in all
      tissues and ascorbic acid in the liver, gills, and brain was verified in carp fed
      with the diet containing 3.0 mg/kg of diphenyl diselenide. This diet had
      advantageous effects for the fish used in experiments. Therefore, this compound
      could be considered a beneficial dietary supplement for carp nutrition.

PMID- 23877623
TI  - Recurrent community-associated Staphylococcus aureus infections in children
      presenting to Texas Children's Hospital in Houston, Texas.
AB  - BACKGROUND: There are limited data characterizing recurrent staphylococcal
      disease in children. We sought to define the clinical features and laboratory
      findings of children with recurrent community-associated Staphylococcus aureus
      infections presenting to Texas Children's Hospital in Houston, TX. METHODS:
      Medical records of children with recurrent, culture-proven community-associated
      S. aureus infections at Texas Children's Hospital from 8/1/2001 to 7/29/2009 were
      reviewed, and antibiotic susceptibility patterns were obtained for all S. aureus
      isolates. RESULTS: Six hundred ninety-four otherwise healthy patients presented
      to Texas Children's Hospital with 2-7 episodes of community-associated S. aureus
      infection, accounting for 1495 encounters, 823 hospitalizations and 3337
      inpatient days. In 90% of patients with <=12 months separating their initial and
      recurrent infections, the methicillin susceptibility of the initial and recurrent
      isolates was the same, compared with 79% of patients with > 12 months separating
      their infections. The overall antibiotic susceptibility pattern did not change
      between isolates in 71% of otherwise healthy children compared with only 33% of
      children with eczema. Ninety-two percent of otherwise healthy children had only
      recurrent skin and soft tissue infections; 8% had >=1 non-skin and soft tissue
      infections. The location of skin and soft tissue infections varied by age, with
      children<=36 months of age being more likely to have >=1 S. aureus infection
      located in the diaper area. CONCLUSIONS: Our study demonstrates that recurrent
      staphylococcal disease requiring emergency center or inpatient care is common,
      accounting for significant utilization of hospital resources. Children with
      recurrent staphylococcal infections are likely to have repeated infections from
      the same staphylococcal strain (by antibiotic susceptibility pattern), indicating
      that persistent colonization, frequent exposure to others who are chronically
      colonized, or environmental contamination is playing a role in recurrent disease.
      Finally, our study emphasizes the need for repeat cultures in children with
      recurrent disease, as 29% of healthy children and 67% of children with a
      predisposing risk factor (such as eczema) have a change in the antibiotic
      susceptibility pattern between S. aureus isolates.

PMID- 23877624
TI  - Concentration, origin and health hazard from fine particle-bound PAH at three
      characteristic sites in Southern Poland.
AB  - Suspended particles with the aerodynamic diameters not greater than 2.5 MUm
      (PM2.5) and 1 MUm (PM1, sub-fraction of PM2.5) were sampled at three sites: an
      urban background site, rural background site, and urban traffic site in southern
      Poland. In total, there were 240 samples taken within 02.08.2009-27.12.2010.
      Fifteen polycyclic aromatic hydrocarbons (PAH) were determined in each dust
      fraction. The averages of the concentration of total PAH (SigmaPAH) and of
      particular PAH, as well as the share of carcinogenic PAH in total PAH
      (SigmaPAHcarc/SigmaPAH), carcinogenic equivalent, mutagenic equivalent, and TCDD
      toxic equivalent appeared high compared to other areas in the world. Their high
      values express the significance of health hazard from PM and PM-bound PAH in
      southern Poland. The diagnostic ratios suggest that PM-bound PAH originate from
      municipal (PM1-2.5) and vehicular (PM1) combustion.

PMID- 23877625
TI  - Assessment of in vivo estrogenic response and identification of environmental
      estrogens in influent and effluent from a sewage treatment plant.
AB  - The in vivo estrogenic response and estrogenic contents of the influent and
      effluent collected from a sewage treatment plant located in Jiaozuo were
      assessed. The bioassay showed significant serum vitellogenin (VTG) induction in
      all the treated male goldfish (Carassius auratus) and significant gonad atrophies
      were only observed in the fish induced the most VTG expressions. Six target
      estrogens (estrone, 17beta-estradiol, 17alpha-ethynylestradiol, 4-n-octylphenol,
      4-n-nonylphenol and bisphenol A) were detected in different polar fractions, with
      the exception of the 25 % and 50 % methanol fractions extracted from the influent
      and the 25 %, 50 %, 95 % and 100 % methanol fractions extracted from the
      effluent. For both the influent and effluent, natural and synthetic steroidal
      estrogens were detected in those extracted fractions induced the most abundant
      VTG expressions.

PMID- 23877626
TI  - Anaerobic treatability of wastewater contaminated with propylene glycol.
AB  - The purpose of this study was to investigate the biodegradability of propylene
      glycol in anaerobic conditions by using methanogenic culture. A master reactor
      was set up to develop a culture that would be acclimated to propylene glycol.
      After reaching steady-state, culture was transferred to serum bottles. Three
      reactors with same initial conditions were run for consistency. Propylene glycol
      was completely biodegradable under anaerobic methanogenic conditions. Semi
      continuous reactors operated at a temperature of 35 degrees C had consistently
      achieved a propylene glycol removal of higher than 95 % based on chemical oxygen
      demand (COD). It was found that in semi-continuous reactors, anaerobic treatment
      of propylene glycol at concentrations higher than 1,500 mg COD m(-3) day(-1) was
      not convenient due to instable effluent COD.

PMID- 23877627
TI  - Effect of two lipid emulsions on reversing high-dose levobupivacaine-induced
      reduced vasoconstriction in the rat aortas.
AB  - The goals of this study were to determine which lipid emulsion (Intralipid((r))
      and Lipofundin MCT/LCT((r))) is more effective in reversing high-dose
      levobupivacaine-induced reduced vasoconstriction in isolated rat aortas and to
      examine the associated cellular mechanisms with a particular focus on the
      endothelium. Two lipid emulsion concentration-response curves were generated
      using high-dose levobupivacaine-induced reduced vasoconstriction and vasodilation
      of isolated aortas pretreated with or without 60 mM KCl. Endothelial nitric oxide
      synthase (eNOS) and caveolin-1 phosphorylation were measured in rat aortic tissue
      treated with levobupivacaine in the presence or absence of lipid emulsion.
      Dichlorofluorescein oxidation, a measure of reactive oxygen species production,
      was measured in lipid emulsion-treated human umbilical vein endothelial cells. In
      levobupivacaine (0.3 mM)-induced reduced vasoconstriction of isolated aorta, the
      magnitude of the Intralipid((r))- and Lipofundin MCT/LCT((r))-mediated reversal
      was not significantly different. Lipid emulsion reversal of levobupivacaine
      induced reduced vasoconstriction was greater in endothelium-intact aortas than in
      endothelium-denuded aortas. The two lipid emulsions similarly inhibited
      levobupivacaine-induced eNOS phosphorylation in aortic tissue. Pretreatment with
      both lipid emulsions increased dichlorofluorescein oxidation. Both
      Intralipid((r)) and Lipofundin MCT/LCT((r)) are equally effective for vascular
      tone recovery from high-dose levobupivacaine-induced reduced vasoconstriction.
      This reversal is mediated partially by decreasing nitric oxide bioavailability. 

PMID- 23877628
TI  - Interaction between AT1 receptor and NF-kappaB in hypothalamic paraventricular
      nucleus contributes to oxidative stress and sympathoexcitation by modulating
      neurotransmitters in heart failure.
AB  - Angiotensin II type 1 receptor (AT1-R) and nuclear factor-kappaB (NF-kappaB) in
      the paraventricular nucleus (PVN) play important roles in heart failure (HF);
      however, the central mechanisms by which AT1-R and NF-kappaB contribute to
      sympathoexcitation in HF are yet unclear. In this study, we determined whether
      interaction between AT1-R and NF-kappaB in the PVN modulates neurotransmitters
      and contributes to NAD(P)H oxidase-dependent oxidative stress and
      sympathoexcitation in HF. Rats were implanted with bilateral PVN cannulae and
      subjected to coronary artery ligation or sham surgery (SHAM). Subsequently,
      animals were treated for 4 weeks through bilateral PVN infusion with either
      vehicle or losartan (LOS, 10 MUg/h), an AT1-R antagonist; or pyrrolidine
      dithiocarbamate (PDTC, 5 MUg/h), a NF-kappaB inhibitor via osmotic minipump.
      Myocardial infarction (MI) rats had higher levels of glutamate (Glu),
      norepinephrine (NE) and NF-kappaB p65 activity, lower levels of gamma
      aminobutyric acid (GABA), and more positive neurons for phosphorylated IKKbeta
      and gp91(phox) (a subunit of NAD(P)H oxidase) in the PVN when compared to SHAM
      rats. MI rats also had higher levels of renal sympathetic nerve activity (RSNA)
      and plasma proinflammatory cytokines (PICs), NE and epinephrine. PVN infusions of
      LOS or PDTC attenuated the decreases in GABA and the increases in gp91(phox), NF
      kappaB activity, Glu and NE, in the PVN of HF rats. PVN infusions of LOS or PDTC
      also attenuated the increases in RSNA and plasma PICs, NE and epinephrine in MI
      rats. These findings suggest that interaction between AT1 receptor and NF-kappaB
      in the PVN contributes to oxidative stress and sympathoexcitation by modulating
      neurotransmitters in heart failure. 

PMID- 23877629
TI  - Novel preparation of chiral alpha-amino acids using the Mitsunobu-Tsunoda
      reaction.
AB  - An efficient synthesis of racemic or optically active alpha-amino acids by
      modified-Mitsunobu alkylation of a racemic or chiral glycine template from
      alcohols was developed. Libraries of amino acids were prepared in moderate to
      good yield with good to high enantioselectivity. This simple method widens the
      scope for preparation of structurally diverse amino acids. 

PMID- 23877630
TI  - Appropriate use and clinical impact of transthoracic echocardiography.
AB  - IMPORTANCE: Transthoracic echocardiography (TTE) accounts for almost half of all
      cardiac imaging services and is a widely available and versatile tool.
      Appropriate use criteria (AUC) for echocardiography were developed to improve
      patient care and health outcomes. Prior studies have shown that most TTEs are
      appropriate by AUC. However, the associations among TTE, AUC, and their clinical
      impact have not been well explored. OBJECTIVES: To describe the proportion of
      TTEs that affect clinical care in an academic medical center overall and in
      subgroups defined as appropriate and inappropriate by AUC. DESIGN AND SETTING:
      Retrospective review of medical records from 535 consecutive TTEs at an academic
      medical center was performed. The TTEs were classified according to 2011 AUC by 2
      cardiologists blinded to clinical impact and were assessed for clinical impact by
      2 cardiologists blinded to AUC. Clinical impact was assigned to 1 of the
      following 3 categories: (1) active change in care, (2) continuation of current
      care, or (3) no change in care. PARTICIPANTS: Five hundred thirty-five patients
      undergoing TTE. EXPOSURE: Transthoracic echocardiography. MAIN OUTCOMES AND
      MEASURES Prevalence of appropriate, inappropriate, and uncertain TTEs and
      prevalence of clinical impact subcategories. RESULTS: Overall, 31.8% of TTEs
      resulted in an active change in care; 46.9%, continuation of current care; and
      21.3%, no change in care. By 2011 AUC, 91.8% of TTEs were appropriate; 4.3%,
      inappropriate; and 3.9%, uncertain. We detected no statistically significant
      difference between appropriate and inappropriate TTEs in the proportion of TTEs
      that led to active change in care (32.2% vs 21.7%; P= .29). CONCLUSIONS AND
      RELEVANCE: Although 9 in 10 TTEs were appropriate by 2011 AUC, fewer than 1 in 3
      TTEs resulted in an active change in care, nearly half resulted in continuation
      of current care, and slightly more than 1 in 5 resulted in no change in care. The
      low rate of active change in care (31.8%) among TTEs mostly classified as
      appropriate (91.8%) highlights the need for a better method to optimize TTE
      utilization to use limited health care resources efficiently while providing high
      quality care.

PMID- 23877631
TI  - Biodistribution and radiation dosimetry in healthy volunteers of a novel tumour
      specific probe for PET/CT imaging: BAY 85-8050.
AB  - PURPOSE: Novel tracers for the diagnosis of malignant disease with PET and PET/CT
      are being developed as the most commonly used (18)F deoxyglucose (FDG) tracer
      shows certain limitations. Employing radioactively labelled glutamate derivatives
      for specific imaging of the truncated citrate cycle potentially allows more
      specific tumour imaging. Radiation dosimetry of the novel tracer BAY 85-8050, a
      glutamate derivative, was calculated and the effective dose (ED) was compared
      with that of FDG. METHODS: Five healthy volunteers were included in the study.
      Attenuation-corrected whole-body PET/CT scans were performed from 0 to 90 min, at
      120 and at 240 min after injection of 305.0 +/- 17.6 MBq of BAY 85-8050. Organs
      with moderate to high uptake at any of the imaging time points were used as
      source organs. Total activity in each organ at each time point was measured. Time
      activity curves (TAC) were determined for the whole body and all source organs.
      The resulting TACs were fitted to exponential equations and accumulated
      activities were determined. OLINDA/EXM software was used to calculate individual
      organ doses and the whole-body ED from the acquired data. RESULTS: Uptake of the
      tracer was highest in the kidneys due to renal excretion of the tracer, followed
      by the pancreas, heart wall and osteogenic cells. The mean organ doses were:
      kidneys 38.4 +/- 11.2 MUSv/MBq, pancreas 23.2 +/- 3.8 MUSv/MBq, heart wall 17.4
      +/- 4.1 MUSv/MBq, and osteogenic cells 13.6 +/- 3.5 MUSv/MBq. The calculated ED
      was 8.9 +/- 1.5 MUSv/MBq. CONCLUSION: Based on the distribution and dose
      estimates, the calculated radiation dose of BAY 85-8050 is 2.67 +/- 0.45 mSv at a
      patient dose of 300 MBq, which compares favourably with the radiation dose of FDG
      (5.7 mSv).

PMID- 23877632
TI  - Hypocalcaemia after treatment with [177Lu-DOTA 0,Tyr3]octreotate.
AB  - PURPOSE: The aim of this study was to explore the possible mechanisms involved in
      an observed decline in serum calcium levels in patients with a neuroendocrine
      tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu
      octreotate). METHODS: In 47 patients with NET who were normocalcaemic at
      baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma
      glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were
      prospectively analysed at baseline and up to 6 months after treatment.
      Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal
      propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal
      crosslinking telopeptide of bone collagen, collagen type I crosslinked N
      telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at
      baseline and at 3 and 6 months. Another 153 patients with NET were included in a
      retrospective study to estimate the occurrence of hypocalcaemia in a larger
      patient group. RESULTS: In the prospectively included patients, the mean serum
      calcium level decreased significantly after treatment (2.31 +/- 0.01 to 2.26 +/-
      0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum
      calcium levels with a nadir of <= 2.10 mmol/l. In five patients (11%), calcium
      substitution therapy was prescribed. PTH increased significantly (5.9 +/- 0.6 to
      6.7 +/- 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum
      calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine
      levels increased significantly (73 +/- 3 to 77 +/- 3 MUmol/l, p = 0.01), but not
      enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the
      retrospectively analysed patients, the mean serum calcium level decreased
      significantly from 2.33 +/- 0.01 at baseline to a nadir of 2.24 +/- 0.01 mmol/l
      at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a
      serum calcium nadir of <= 2.10 mmol/l, and 11 (7%) received calcium substitution
      therapy. CONCLUSION: The mean serum calcium level decreased significantly after
      treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20%
      of patients. We excluded several potential causes of this hypocalcaemia, so the
      cause remains unknown. Serum calcium levels should be monitored after peptide
      receptor radionuclide therapy, and calcium substitution therapy should be
      initiated if appropriate.

PMID- 23877633
TI  - (18)F-FDG PET/CT predicts survival in patients with inflammatory breast cancer
      undergoing neoadjuvant chemotherapy.
AB  - PURPOSE: The objective of this study was to evaluate the role of (18)F-FDG PET/CT
      in predicting overall survival in inflammatory breast cancer patients undergoing
      neoadjuvant chemotherapy. METHODS: Included in this retrospective study were 53
      patients with inflammatory breast cancer who had at least two PET/CT studies
      including a baseline study before the start of neoadjuvant chemotherapy.
      Univariate and multivariate analyses were performed to assess the effects on
      survival of the following factors: tumor maximum standardized uptake value
      (SUVmax) at baseline, preoperatively and at follow-up, decrease in tumor SUVmax,
      histological tumor type, grade, estrogen, progesterone, HER2/neu receptor status,
      and extent of disease at presentation including axillary nodal and distant
      metastases. RESULTS: By univariate analysis, survival was significantly
      associated with decrease in tumor SUVmax and tumor receptor status. Patients with
      decrease in tumor SUVmax had better survival (P = 0.02). Patients with a triple
      negative tumor (P = 0.0006), a Her2/neu-negative tumor (P = 0.038) or an ER
      negative tumor (P = 0.039) had worse survival. Multivariate analysis confirmed
      decrease in tumor SUVmax and triple-negative receptor status as significant
      predictors of survival. Every 10% decrease in tumor SUVmax from baseline
      translated to a 15% lower probability of death, and complete resolution of tumor
      FDG uptake translated to 80% lower probability of death (P = 0.014). Patients
      with a triple-negative tumor had 4.11 times higher probability of death (P =
      0.004). CONCLUSION: Decrease in tumor SUVmax is an independent predictor of
      survival in patients with inflammatory breast cancer undergoing neoadjuvant
      chemotherapy. Further investigation with prospective studies is warranted to
      clarify its role in assessing response and altering therapy.

PMID- 23877634
TI  - 18F-Fluoride PET/CT in the detection of bone metastases in clear cell renal cell
      carcinoma: discordance with bone scintigraphy.

PMID- 23877635
TI  - Multiple skeletal lesions on FDG PET in severe primary hyperparathyroidism.

PMID- 23877636
TI  - Heme oxygenase-1 gene variants and hyperbilirubinemia risk in North Indian
      newborns.
AB  - Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in bilirubin metabolism, and
      its genetic variant may modulate hyperbilirubinemia risk in neonates. The aim of
      the present study was to assess the association between heme oxygenase-1 gene
      variants and hyperbilirubinemia risk in Indian newborns. In a prospective case
      control study, we analyzed (GT)n repeats and g.-413A>T variant of HO-1 gene and
      UGT1A1 gene variants in 100 case newborns with total serum bilirubin (TSB) levels
      exceeding 95th percentile and 100 control newborns with TSB levels below 75th
      percentile on the hour-specific bilirubin nomogram of the American Academy of
      Pediatrics. Study population consisted of term (37-41 weeks) and late preterm (34
      36 weeks) newborns during the first 2 weeks of age. In our analysis, the (GT)n
      allele was highly polymorphic, ranging in number from 15 to 40. The incidence of
      short (GT)n allele (<= 20) was significantly higher in neonates with
      hyperbilirubinemia than in controls. Although g.-413A>T variant was widely
      prevalent in the study population, no difference was noted in its prevalence
      between cases and controls. Short (GT)n repeats of HO-1 gene, c.211G>A variant of
      UGT1A1 gene, and excessive weight loss were independent risk factors for neonatal
      hyperbilirubinemia. In the presence of two or more risk factors, the odds of
      developing neonatal hyperbilirubinemia were high. Shorter (GT)n genotype in the
      promoter region of HO-1 gene is significantly associated with hyperbilirubinemia
      risk in Indian newborns. This genotype may interact with other genetic and
      clinical risk factors to further potentiate hyperbilirubinemia risk in newborns.

PMID- 23877637
TI  - Use of analgesic and sedative drugs in VLBW infants in German NICUs from 2003
      2010.
AB  - Very low birth weight (VLBW) infants frequently receive analgesia and/or sedation
      for painful procedures and mechanical ventilation to avoid negative stress. Yet,
      concerns remain regarding potential adverse long-term effects of these drugs on
      VLBW infants' neurocognitive outcome. Recent studies have shown that less
      invasive surfactant application (LISA) and early nasal CPAP treatment reduce the
      need for mechanical ventilation and painful procedures. Therefore, these measures
      might also reduce the application of analgesic and/or sedative drugs in VLBW
      infants. To evaluate this hypothesis and to identify potential changes in
      analgesic treatment concepts in recent years, we retrospectively analyzed data on
      analgesia and sedation, respiratory support, and the method of surfactant
      application in VLBW infants enrolled in the German Neonatal Network (GNN) trial
      between 2003 and 2009 (period 1) and compared it with data from infants
      participating in GNN in 2010 (period 2). In both periods, about one third of all
      infants were treated with analgesic and/or sedative drugs using a wide variety of
      substances. The administration of novel drugs such as propofol, sufentanil, or
      intravenous paracetamol was higher in 2010 (6.7 vs. 12.2 %). Infants who were
      treated with CPAP only received significantly less analgesic/sedative medication
      than infants who were mechanically ventilated (12 vs. 65 %, p=<0.001). Similarly,
      infants treated with LISA received less analgesic or sedative drugs as compared
      to infants who received surfactant via endotracheal intubation (36 vs. 63 %,
      p=0.001). CONCLUSION: Although both avoidances of mechanical ventilation and less
      invasive surfactant application are associated with reduced analgesic or sedative
      treatment, the percentage of VLBW infants who received analgesia and/or sedation
      remained unchanged in Germany in recent years.

PMID- 23877638
TI  - A possible mechanism for 2,3',4,4',5'-pentachlorobiphenyl-mediated decrease in
      serum thyroxine level in mice.
AB  - The effect of 2,3',4,4',5'-pentachlorobiphenyl (CB118) on serum total thyroxine
      (T4) level was comparatively examined between C57BL/6 and DBA/2 mice, which are
      sensitive and insensitive, respectively, to aryl hydrocarbon receptor-mediated
      biological changes. After 5 d of CB118 administration (50 mg/kg,
      intraperitoneally (i.p.)), the serum total T4 levels in both strains of mice were
      markedly decreased. However, significant decreases in serum thyroid-stimulating
      hormone levels were observed in DBA/2 mice, but not in C57BL/6 mice. In contrast,
      significant increases in the level and activity of hepatic T4-uridine 5'
      diphosphate (UDP)-glucuronosyltransferase by CB118 treatment were observed only
      in C57BL/6 mice. Likewise, significant increases in the amounts of biliary
      [(125)I]T4 and [(125)I]T4-glucuronide after injection of [(125)I]T4 were observed
      only in the CB118-pretreated C57BL/6 mice. The CB118-mediated changes in the
      levels of [(125)I]T4 bound to transthyretin (TTR), albumin, and thyroxine binding
      globulin (TBG) were also observed in C57BL/6 mice, but not in DBA/2 mice. Despite
      such strain differences, significant increases in the liver-selective
      accumulation of [(125)I]T4 by CB118-pretreatment was observed in both C57BL/6 and
      DBA/2 mice. The present findings indicate that CB118-mediated decreases in levels
      of serum T4 in C57BL/6 and DBA/2 mice occur mainly through enhanced accumulation
      of hepatic T4.

PMID- 23877643
TI  - Movement disorders: novel FUS gene variants linked to essential tremor.

PMID- 23877644
TI  - Neurodegenerative disease: defective mitochondrial dynamics in the hot seat-a
      therapeutic target common to many neurological disorders?

PMID- 23877645
TI  - Dementia: Mild cognitive impairment--amyloid and beyond.

PMID- 23877646
TI  - Developing and Trialling an independent, scalable and repeatable IT-benchmarking
      procedure for healthcare organisations.
AB  - BACKGROUND: Continuous improvements of IT-performance in healthcare organisations
      require actionable performance indicators, regularly conducted, independent
      measurements and meaningful and scalable reference groups. Existing IT
      benchmarking initiatives have focussed on the development of reliable and valid
      indicators, but less on the questions about how to implement an environment for
      conducting easily repeatable and scalable IT-benchmarks. OBJECTIVES: This study
      aims at developing and trialling a procedure that meets the afore-mentioned
      requirements. METHODS: We chose a well established, regularly conducted (inter-)
      national IT-survey of healthcare organisations (IT-Report Healthcare) as the
      environment and offered the participants of the 2011 survey (CIOs of hospitals)
      to enter a benchmark. The 61 structural and functional performance indicators
      covered among others the implementation status and integration of IT-systems and
      functions, global user satisfaction and the resources of the IT-department.
      Healthcare organisations were grouped by size and ownership. The benchmark
      results were made available electronically and feedback on the use of these
      results was requested after several months. RESULTS: Fifty-ninehospitals
      participated in the benchmarking. Reference groups consisted of up to 141 members
      depending on the number of beds (size) and the ownership (public vs. private). A
      total of 122 charts showing single indicator frequency views were sent to each
      participant. The evaluation showed that 94.1% of the CIOs who participated in the
      evaluation considered this benchmarking beneficial and reported that they would
      enter again. Based on the feedback of the participants we developed two
      additional views that provide a more consolidated picture. CONCLUSION: The
      results demonstrate that establishing an independent, easily repeatable and
      scalable IT-benchmarking procedure is possible and was deemed desirable. Based on
      these encouraging results a new benchmarking round which includes process
      indicators is currently conducted.

PMID- 23877647
TI  - The diversity of BVDV subgenotypes in a vaccinated dairy cattle herd in Brazil.
AB  - Bovine viral diarrhoea virus (BVDV) is an important pathogen of cattle that
      occurs worldwide with substantial economic impact on beef and dairy industries.
      The aim of this study was to describe the diversity of BVDV subgenotypes in
      persistently infected (PI) animals identified in a highly productive, regularly
      vaccinated, dairy cattle herd presenting with reproductive failure. Serum samples
      were collected from all animals within the herd (n = 692) and used to detect the
      presence of BVDV RNA. Using reverse transcription polymerase chain reaction
      assay, 29 cows were identified as transiently infected, three animals (two cows
      and one calf) as persistently infected, and one calf as putative BVDV PI animal.
      The sequences of 5'UTR and/or N(pro) gene of BVDV used in phylogenetic analyses
      revealed that the three PI animals were infected by three different BVDV
      subgenotypes (BVDV-1a, BVDV-1b, and BVDV-1d). These results demonstrated that in
      an open dairy cattle herd, regular vaccination against BVDV by itself is not able
      to prevent viral circulation in the herd. Furthermore, depending on the frequency
      of the acquisition of heifers and/or cows for replacement, several BVDV
      subgenotypes may co-exist simultaneously in the same herd. 

PMID- 23877648
TI  - Expression and characterization of the first snail-derived UDP-N-acetyl-alpha-D
      galactosamine:polypeptide N-acetylgalactosaminyltransferase.
AB  - UDP-GalNAc:polypeptide GalNAc transferase (ppGalNAcT; EC 2.4.1.41) catalyzes the
      first step in mucin-type O-glycosylation. To date, several members of this large
      enzyme family have been analyzed in detail. In this study we present cloning,
      expression and characterization of the first representative of this type of
      glycosyltransferase from mollusk origin, namely from Biomphalaria glabrata. The
      full length sequence of the respective gene was obtained by screening of a cDNA
      library using homology-based PCR. The entire gene codes for a protein consisting
      of 600 amino acids comprising the features of a typical type II membrane protein
      containing a cytoplasmic tail at the N-terminus, a transmembrane and a catalytic
      domain as well as a ricin-like motif at the C-terminus. Sequence comparison with
      ppGalNAcTs from various species revealed high similarities in terms of structural
      architecture. The enzyme is O-glycosylated but does not have any putative N
      glycosylation sites. All four tested acceptor peptides were functional
      substrates, with Muc2 being the best one. Further biochemical parameters tested,
      confirmed a close relationship to the family of yet known ppGalNAcTs.

PMID- 23877649
TI  - An anti-sulfatide antibody O4 immunoprecipitates sulfatide rafts including Fyn,
      Lyn and the G protein alpha subunit in rat primary immature oligodendrocytes.
AB  - The association of sulfatide with specific proteins in oligodendrocytes was
      examined by co-immunoprecipitation with an anti-sulfatide antibody. Protein
      kinase activity was detected in precipitates with a monoclonal antibody to
      sulfatide (O4) from the rat primary immature oligodendrocytes. We conducted in
      vitro kinase assay of tyrosine phosphorylated proteins of 80, 59, 56, 53 and 40
      kDa by gel electrophoresis. Of these proteins, the proteins of 59 kDa and 53/56
      kDa were identified as the Src family tyrosine kinases Fyn and Lyn on the basis
      of their sequential immunoprecipitation with anti-Fyn and anti-Lyn antibodies,
      respectively. The 40 kDa protein was identified as the alpha subunit of the
      heterotrimeric G protein. These observations suggest that O4 immunoprecipitates
      sulfatide rafts including Fyn, Lyn and the alpha subunit of the heterotrimeric G
      protein.

PMID- 23877650
TI  - Morphological and functional changes in a new animal model of Meniere's disease.
AB  - The purpose of this study was to clarify the underlying mechanism of vertiginous
      attacks in Meniere's disease (MD) while obtaining insight into water homeostasis
      in the inner ear using a new animal model. We conducted both histopathological
      and functional assessment of the vestibular system in the guinea-pig. In the
      first experiment, all animals were maintained 1 or 4 weeks after
      electrocauterization of the endolymphatic sac of the left ear and were given
      either saline or desmopressin (vasopressin type 2 receptor agonist). The temporal
      bones from both ears were harvested and the extent of endolymphatic hydrops was
      quantitatively assessed. In the second experiment, either 1 or 4 weeks after
      surgery, animals were assessed for balance disorders and nystagmus after the
      administration of saline or desmopressin. In the first experiment, the proportion
      of endolymphatic space in the cochlea and the saccule was significantly greater
      in ears that survived for 4 weeks after surgery and were given desmopressin
      compared with other groups. In the second experiment, all animals that underwent
      surgery and were given desmopressin showed spontaneous nystagmus and balance
      disorder, whereas all animals that had surgery but without desmopressin
      administration were asymptomatic. Our animal model induced severe endolymphatic
      hydrops in the cochlea and the saccule, and showed episodes of balance disorder
      along with spontaneous nystagmus. These findings suggest that administration of
      desmopressin can exacerbate endolymphatic hydrops because of acute V2
      (vasopressin type 2 receptor)-mediated effects, and, when combined with
      endolymphathic sac dysfunction, can cause temporary vestibular abnormalities that
      are similar to the vertiginous attacks in patients with MD.

PMID- 23877651
TI  - Substrate specificity of an oxygen dependent sulfoxide synthase in ovothiol
      biosynthesis.
AB  - OvoA is an iron(II) dependent sulfoxide synthase which catalyzes the first step
      in ovothiol A biosynthesis. This enzyme sulphurizes the C5 position of the
      imidazole side chain of L-histidine. We report the substrate specificity profile
      of this catalyst and present data which indicate that OvoA catalysis follows an
      thiol-ene type mechanism.

PMID- 23877652
TI  - Strontium-89 (Sr-89) chloride in the treatment of various cancer patients with
      multiple bone metastases.
AB  - BACKGROUND: Although the use of Sr-89 chloride in the treatment of patients with
      prostate and breast cancer has been widely reported, little information is
      available about its use for other malignancies. Here, we retrospectively analyzed
      the clinical profile of Sr-89 chloride in various patients with painful bone
      metastases. METHODS: Entry criteria were a pathologically proven malignancy,
      clinically diagnosed multiple bone metastases, and adequate organ function. Sr-89
      chloride (Metastron) was given by single intravenous infusion at 2 MBq/kg over 2
      min. Self-reported outcome measures were used as a response index, including pain
      diary data on a 0-10 numeric rating scale (NRS). RESULTS: Fifty-four consecutive
      patients with painful bone metastases were treated with Sr-89 chloride at the
      National Cancer Center Hospital East between March 2009 and July 2011, consisting
      of 26 with breast/prostate cancer and 28 with other malignancies (lung 8, head
      and neck 6, colorectal 6, others 8). Thirteen (24 %) patients experienced a
      transient increase in pain, which was categorized as a flare-up response. Grade 3
      4 anemia was observed in 6 patients, 3 of whom required blood transfusion.
      Regarding efficacy, response rates and complete response rates were 71.2 % and
      34.6 %, respectively, and time to response from the initiation of treatment was
      36 days (range, 13-217). No significant difference in response rates was seen
      between patients with breast/prostate cancer and other cancers (breast/prostate
      69.2 %, other 73.1 %; p = 0.76). CONCLUSIONS: As in patients with breast and
      prostate cancer, Sr-89 chloride is a promising agent for the treatment of painful
      bone metastases in patients with various other malignancies.

PMID- 23877656
TI  - Quantitative understanding of thermal stability of alpha''-Fe16N2.
AB  - The thermal stability of alpha''-Fe16N2, which attracts much interest because of
      its superior magnetic properties featuring a large magnetocrystalline anisotropy
      (Ku ~ 1 * 10(7) erg cm(-3)) and a large saturation magnetization (Ms ~ 234 emu g(
      1)), though unfortunately thermally unstable, has been quantitatively studied.

PMID- 23877653
TI  - Assessment of (18)F-fluorodeoxyglucose positron emission tomography combined with
      computed tomography in the preoperative management of patients with gastric
      cancer.
AB  - BACKGROUND: The significance of (18)F-2-deoxy-2-fluoro-glucose positron emission
      tomography combined with computed tomography imaging (FDG-PET/CT) in the
      diagnosis of gastric cancer remains controversial. This study aimed to evaluate
      the efficacy of preoperative FDG-PET/CT in staging of gastric cancer. METHODS:
      FDG-PET/CT results for 90 patients with gastric cancer were retrospectively
      examined. For quantitative PET analysis, FDG uptake was assessed based on the
      maximum standardized uptake values (SUVmax). RESULTS: FDG-PET/CT detected the
      primary gastric cancer in 71 of the 90 patients (sensitivity 78.9 %). The median
      SUVmax was significantly higher in patients with T3/T4 disease than in those with
      T1/T2 (9.0 vs. 3.8; P < 0.001), in patients with distant metastasis than in those
      with no metastasis (9.5 vs. 7.7; P = 0.018), and with stage III/IV tumors than in
      those with stage I/II (9.0 vs. 4.7; P = 0.017). The SUVmax of the primary tumor
      was significantly correlated with tumor size (r = 0.461, P < 0.001). The
      sensitivity, specificity, and accuracy of FDG-PET/CT in assessing metastasis to
      regional lymph nodes were 64.5, 85.7, and 71.1 %, respectively. CONCLUSIONS: FDG
      PET/CT results are significantly associated with tumor progression in gastric
      cancer, and such findings can reliably identify cancer cell populations.

PMID- 23877655
TI  - Enhanced immunotherapeutic effect of modified HPV16 E7-pulsed dendritic cell
      vaccine by an adeno-shRNA-SOCS1 virus.
AB  - Cervical cancer is the second most common cause of cancer-related deaths among
      women worldwide. However, no efficient therapy exists against cervical cancer and
      current treatments have several disadvantages. One possible novel approach is to
      develop immune-based strategies using tumor antigen-loaded dendritic cells (DCs)
      for the induction of cellular antitumor immunity. In this study, we created a
      modified HPV16 E7, HPV16mE7, to reduce its transformation activity and to enhance
      its antigenicity. The siRNA delivery technique was used to silence the suppressor
      of cytokine signaling 1 (SOCS1) gene in DCs. BM-derived DCs infected by ad-shRNA
      SOCS1 were pulsed with the HPV16mE7 protein and then were transfused into mouse
      models bearing TC-1 tumor cells expressing HPV16 E6/E7. IFN-gamma, cytokine (TNF
      alpha, IL-12, IL-6) expression, anti-E7 antibody and cytotoxic T lymphocyte (CTL)
      levels were measured. The survival rate, survival days and the tumor volume of
      the mouse models from the different treatment groups were monitored. The data
      showed that the mE7-pulsed DC vaccine enhanced by adenovirus-mediated SOCS1
      silencing exhibited better immunotherapeutic effect on the allografted tumor
      mouse models. The method by silencing SOCS1 in HPV16mE7 protein-pulsed DCs may
      provide a new strategy for the development of safe and effective immunotherapy
      for cervical cancer. 

PMID- 23877657
TI  - Perturbation of proteasome function by bortezomib leading to ER stress-induced
      apoptotic cell death in cholangiocarcinoma.
AB  - PURPOSE: Cholangiocarcinoma (CCA) or cancer of the biliary tract is
      heterogeneous; however, chronic inflammatory-related features are unique in CCA.
      Moreover, the genes involved in proteasome functions are evidently increased in
      CCA. Hence, CCA might be vulnerable to endoplasmic reticulum (ER) stressors,
      particularly a proteasome inhibitor. Therefore, bortezomib (BTZ), a specific 26S
      proteasome inhibitor, was selected, and its antitumor effects against CCA were
      investigated. METHODS: Liver fluke-associated CCA cell lines were used. Cell
      proliferation and apoptosis detection were determined by a tetrazolium-based
      assay, caspase detection and annexin V binding assay. The accumulations of
      proteasome substrates, the inductions of ER stress and unfolded protein response
      (UPR) proteins were demonstrated by western blot and reporter systems. The in
      vivo anti-proliferative effect was accessed in a subcutaneous transplantation
      mouse model. RESULTS: BTZ inhibited CCA proliferation and induced caspase
      dependent apoptosis, independently of the NF-kappaB pathway. Inhibition of
      protein degradation by BTZ led to the induction of UPR; induction of XBP1
      splicing, ATF6 proteolysis and nuclear ATF4 as well as BiP and CHOP expressions
      were evident. Nevertheless, ER stress-induced UPR was overwhelming, leading to
      the activation of apoptosis demonstrated by proteolytic cleavages of ER-related
      caspase 4 and 12 as well as classical caspase 8, 9 and 3. The growth inhibitory
      effect of BTZ was supported by an in vivo model. CONCLUSION: BTZ treatment could
      be a promising therapeutic approach for CCA treatment.

PMID- 23877658
TI  - Efficient ROSA26-based conditional and/or inducible transgenesis using RMCE
      compatible F1 hybrid mouse embryonic stem cells.
AB  - The conditional Cre/loxP system and/or the doxycycline (Dox) inducible Tet-on/off
      system are widely used in mouse transgenesis but often require time consuming,
      inefficient cloning/screening steps and extensive mouse breeding strategies. We
      have therefore developed a highly efficient Gateway- and recombinase-mediated
      cassette exchange (RMCE)-compatible system to target conditional and/or inducible
      constructs to the ROSA26 locus of F1 hybrid Bl6/129 ESCs, called G4 ROSALUC ESCs.
      By combining the Cre/loxP system with or without the inducible Tet-on system
      using Gateway cloning, we can rapidly generate spatial and/or temporal
      controllable gain-of-function constructs that can be targeted to the RMCE
      compatible ROSA26 locus of the G4 ROSALUC ESCs with efficiencies close to 100 %.
      These novel ESC-based technologies allow for the creation of multiple gain-of
      function conditional and/or inducible transgenic ESC clones and mouse lines in a
      highly efficient and locus specific manner. Importantly, incorporating insulator
      sequences into the Dox-inducible vector system resulted in robust, stable
      transgene expression in undifferentiated ESCs but could not fully overcome
      transgene mosaicism in the differentiated state.

PMID- 23877659
TI  - Vaccination of castration-resistant prostate cancer patients with TroVax (MVA
      5T4) in combination with docetaxel: a randomized phase II trial.
AB  - The attenuated vaccinia virus, modified vaccinia Ankara, has been engineered to
      deliver the tumor antigen 5T4 (TroVax(r)). Here, we report results from a
      randomized open-label phase II trial in castration-resistant prostate cancer
      patients in which TroVax was administered in combination with docetaxel and
      compared against docetaxel alone. The aim was to recruit 80 patients (40 per
      arm), but the study was terminated early due to recruitment challenges.
      Therefore, this paper reports the comparative safety and immunological and
      clinical efficacy in 25 patients, 12 of whom were treated with TroVax plus
      docetaxel and 13 with docetaxel alone. 5T4-specific immune responses were
      monitored throughout the study. Clinical responses were assessed by measuring
      changes in tumor burden by CT and bone scan and by quantifying PSA
      concentrations. TroVax was well tolerated in all patients. Of 10 immunologically
      evaluable patients, 6 mounted 5T4-specific antibody responses. Patients treated
      with TroVax plus docetaxel showed a greater median progression-free survival of
      9.67 months compared with 5.10 months for patients on the docetaxel alone arm (P
      = 0.097; HR = 0.31; 95% CI 0.08-1.24). Importantly, a pre-treatment biomarker
      previously demonstrated to predict 5T4 immune response and treatment benefit
      showed a strong association with 5T4 antibody response and a statistically
      significant association with progression-free survival in patients treated with
      TroVax plus docetaxel, but not docetaxel alone.

PMID- 23877661
TI  - Reply to the comments of Sudhir Khanna to the article: Holmium laser division of
      the suture causing entrapment of a drainage tube after laparoscopic nephrectomy.

PMID- 23877660
TI  - [In vitro analysis of the impact of metal ions on human lymphocyte cultures].
AB  - The use of metal implants has become increasingly more frequent in all fields of
      medicine throughout the past decades. Numerous studies have demonstrated that
      metal ions released from these implants can be detected in body fluids remote
      from the implants. Although diseases directly linked to the release of these ions
      seem to be rare, the general public is unsettled. In this study we aimed to
      analyze the impact of molybdenum(V), cobalt(II), chromium(III) and nickel(II)
      ions on cell surface markers (CD25, CD38, CD69, CD95) and viability (7
      AAD/AnnexinV) of human CD4+ T-lymphocytes in vitro. Cobalt(II) ions at a
      concentration of 1000 MUg/l led to a significant suppression of lymphocyte
      activation markers while nickel(II), chromium(III) and molybdenum(V) did not show
      any significant impact on these lymphocyte activation markers. Cell viability was
      significantly reduced by all metal ions, whereas cobalt(II) led to the highest
      increase of apoptotic cells and was the only metal ion to significantly increase
      the necrosis rate. While the pathophysiological significance of these findings
      remains unclear, they are in favour of further research in this field. 

PMID- 23877662
TI  - Urinary protein patterns in patients with Balkan endemic nephropathy.
AB  - PURPOSE: Urinary excretion of beta2-microglobulin (beta2-MG), albumin,
      immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic
      nephropathy (BEN), glomerulonephritis (GN) and healthy controls. METHODS: The
      proteins were measured in morning urine samples from 74 patients with BEN, 50
      healthy persons and 22 patients with GN. RESULTS: In BEN patients, median values
      for albumin, beta2-MG and protein were above upper normal limits, but median IgG
      was inside normal range. All patients with GN had microalbuminuria (MAU) and half
      of them had increased urinary beta2-MG, which was also found in eleven patients
      with increased urinary IgG. In BEN patients, there were significant negative
      correlations between eGFR and all measured urinary proteins, the composition of
      which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73
      m(2) isolated beta2-MG was the most frequent finding (10/12 patients), but MAU
      was present in 4/12 patients. In BEN patients with eGFR between 30 and 59
      ml/min/1.73 m(2), beta2-MG appeared as often as the combination of beta2-MG and
      albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m(2)
      15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or
      albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30
      ml/min/1.73 m(2) only 1/25 had isolated beta2-MG but increased urinary IgG with
      increased beta2-MG, and albumin was the most frequent. CONCLUSION: Although low
      molecular weight proteinuria was the most frequent urinary finding in BEN
      patients, MAU was frequently detected in advanced stages of BEN but also in some
      patients with eGFR > 60 ml/min/1.73 m(2). IgG was increasingly found as eGFR
      decreased.

PMID- 23877664
TI  - A single institutional experience of conversion of non-tunneled to tunneled
      hemodialysis catheters: a comparison to de novo placement.
AB  - PURPOSE: To compare the outcomes of conversion of non-tunneled to tunneled
      hemodialysis catheters with de novo placement of tunneled catheters and to
      determine the effect of time to conversion of non-tunneled to tunneled catheters
      on the incidence of complications. MATERIALS AND METHODS: A retrospective data
      analyses was performed on 1,154 patients who had de novo placement of tunneled
      hemodialysis catheters (control group) and 254 patients who underwent conversion
      of non-tunneled to tunneled catheters (study group). The outcomes including
      technical complications, infection, and catheter dysfunction were compared
      between the two groups. RESULTS: The technical success rate was 100 % in both the
      groups with no complications recorded at the time of procedure or within 24 h of
      insertion. The most common complication encountered in both the groups was
      catheter dysfunction (15.6 % in controls and 18.1 % in study). Infection
      rates/100 catheter days for the control and study groups were 0.17 and 0.19,
      respectively. Infection-free survival was not statistically different between the
      two groups. The time spent with non-tunneled catheter prior to conversion did not
      significantly alter the rates of catheter dysfunction and infection in the study
      group. CONCLUSION: The efficacy and safety of conversion of non-tunneled to
      tunneled hemodialysis catheters are similar to de novo placement with no
      difference in the rates of technical success, catheter dysfunction, or infection.
      However, the exchange of non-tunneled to tunneled catheter can help in
      preservation of veins for future vascular access, which is of vital importance in
      patients with chronic renal disease.

PMID- 23877665
TI  - Limiting "evergreening" for a better balance of drug innovation incentives.

PMID- 23877663
TI  - Validation of the prognostic value of lymph node ratio in patients with penile
      squamous cell carcinoma: a population-based study.
AB  - PURPOSE: The aim of this study was to validate the prognostic value of lymph node
      ratio (LNR), the proportion of metastatic among removed lymph nodes, for patients
      with penile squamous cell carcinoma in a population-based database. METHODS: A
      total of 210 eligible patients with node-positive disease were identified from
      the surveillance epidemiology end results database. Cancer-specific survival
      (CSS) was the clinical outcome of interest. The prognostic ability of LNR was
      assessed by Cox regression analyses. Logrank test was used to compare CSS between
      low-risk and high-risk groups stratified by cutoff points of LNR. RESULTS: The
      median number of LNs removed was 16, and the median value of LNR was 0.20. First,
      LNR was a significant prognostic factor of CSS in univariate analysis (HR =
      4.08). Second, LNR retained independent predictive ability (HR = 6.74) in the
      multivariate model including demographic data, disease characteristics and number
      based LN variables. Addition of LNR remarkably improved the predictive accuracy
      and clinical usefulness of the survival model. Third, maximum stratification of
      CSS can be achieved at the cutoff point of 0.33. CONCLUSION: In the population
      based study, LNR outperformed number-based LN variables for predicting CSS of
      node-positive penile cancer. The ratio-based prognostic factor stresses the
      important role of adequate LND and identification of metastatic LNs in the
      community setting.

PMID- 23877666
TI  - Chair of Wi-Fi safety panel steps down.

PMID- 23877667
TI  - Nearly 1.3 billion have health insurance in China, but poor still neglected.

PMID- 23877668
TI  - Taking care of sick patients.

PMID- 23877670
TI  - Drug could stop PTSD before it starts.

PMID- 23877669
TI  - Characteristics of primary care practices associated with high quality of care.
AB  - BACKGROUND: No primary practice care model has been shown to be superior in
      achieving high-quality primary care. We aimed to identify the organizational
      characteristics of primary care practices that provide high-quality primary care.
      METHODS: We performed a cross-sectional observational study involving a
      stratified random sample of 37 primary care practices from 3 regions of Quebec.
      We recruited 1457 patients who had 1 of 2 chronic care conditions or 1 of 6
      episodic care conditions. The main outcome was the overall technical quality
      score. We measured organizational characteristics by use of a validated
      questionnaire and the Team Climate Inventory. Statistical analyses were based on
      multilevel regression modelling. RESULTS: The following characteristics were
      strongly associated with overall technical quality of care score: physician
      remuneration method (27.0; 95% confidence interval [CI] 19.0-35.0), extent of
      sharing of administrative resources (7.6; 95% CI 0.8-14.4), presence of allied
      health professionals (15.3; 95% CI 5.4-25.2) and/or specialist physicians (19.6;
      95% CI 8.3-30.9), the presence of mechanisms for maintaining or evaluating
      competence (7.7; 95% CI 3.0-12.4) and average organizational access to the
      practice (4.9; 95% CI 2.6-7.2). The number of physicians (1.2; 95% CI 0.6-1.8)
      and the average Team Climate Inventory score (1.3; 95% CI 0.1-2.5) were modestly
      associated with high-quality care. INTERPRETATION: We identified a common set of
      organizational characteristics associated with high-quality primary care. Many of
      these characteristics are amenable to change through practice-level
      organizational changes.

PMID- 23877671
TI  - Concussion.

PMID- 23877672
TI  - Concussions and their consequences: current diagnosis, management and prevention.

PMID- 23877673
TI  - Reporting of joint-replacement outcomes lacking.

PMID- 23877674
TI  - Teenage health scientists honoured.

PMID- 23877675
TI  - Antimicrobial activity of high-mobility-group box 2: a new function to a well
      known protein.
AB  - The human intestinal tract is highly colonized by a vast number of
      microorganisms. Despite this permanent challenge, infections remain rare, due to
      a very effective barrier defense system. Essential effectors of this system are
      antimicrobial peptides and proteins (AMPs), which are secreted by intestinal
      epithelial and lymphoid cells, balance the gut microbial community, and prevent
      the translocation of microorganisms. Several antimicrobial proteins have already
      been identified in the gut. Nonetheless, we hypothesized that additional AMPs are
      yet to be discovered in this setting. Using biological screening based on
      antimicrobial function, here we identified competent antibacterial activity of
      high-mobility-group box 2 (HMGB2) against Escherichia coli. By recombinant
      expression, we confirmed this biologically new antimicrobial activity against
      different commensal and pathogenic bacteria. In addition, we demonstrated that
      the two DNA-binding domains (HMG boxes A and B) are crucial for the antibiotic
      function. We detected HMGB2 in several gastrointestinal tissues by mRNA analysis
      and immunohistochemical staining. In addition to the nuclei, we also observed
      HMGB2 in the cytoplasm of intestinal epithelial cells. Furthermore, HMGB2 was
      detectable in vitro in the supernatants of two different cell types, supporting
      an extracellular function. HMGB2 expression was not changed in inflammatory bowel
      disease but was detected in certain stool samples of patients, whereas it was
      absent from control individuals. Taken together, we characterized HMGB2 as an
      antimicrobial protein in intestinal tissue, complementing the diverse repertoire
      of gut mucosal defense molecules. 

PMID- 23877676
TI  - Candida tropicalis antifungal cross-resistance is related to different azole
      target (Erg11p) modifications.
AB  - Candida tropicalis ranks between third and fourth among Candida species most
      commonly isolated from clinical specimens. Invasive candidiasis and candidemia
      are treated with amphotericin B or echinocandins as first-line therapy, with
      extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is
      usually susceptible to all antifungal agents, although several azole drug
      resistant clinical isolates are being reported. However, C. tropicalis resistant
      to amphotericin B is uncommon, and only a few strains have reliably demonstrated
      a high level of resistance to this agent. The resistance mechanisms operating in
      C. tropicalis strains isolated from clinical samples showing resistance to azole
      drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal
      drug resistance was related to mutations of the azole target (Erg11p) with or
      without alterations of the ergosterol biosynthesis pathway. The antifungal drug
      resistance shown in vitro correlated very well with the results obtained in vivo
      using the model host Galleria mellonella. Using this panel of strains, the G.
      mellonella model system was validated as a simple, nonmammalian minihost model
      that can be used to study in vitro-in vivo correlation of antifungals in C.
      tropicalis. The development in C. tropicalis of antifungal drug resistance with
      different mechanisms during antifungal treatment has potential clinical impact
      and deserves specific prospective studies. 

PMID- 23877677
TI  - Structures of the class D Carbapenemases OXA-23 and OXA-146: mechanistic basis of
      activity against carbapenems, extended-spectrum cephalosporins, and aztreonam.
AB  - Class D beta-lactamases that hydrolyze carbapenems such as imipenem and doripenem
      are a recognized danger to the efficacy of these "last-resort" beta-lactam
      antibiotics. Like all known class D carbapenemases, OXA-23 cannot hydrolyze the
      expanded-spectrum cephalosporin ceftazidime. OXA-146 is an OXA-23 subfamily
      clinical variant that differs from the parent enzyme by a single alanine (A220)
      inserted in the loop connecting beta-strands beta5 and beta6. We discovered that
      this insertion enables OXA-146 to bind and hydrolyze ceftazidime with an
      efficiency comparable to those of other extended-spectrum class D beta
      lactamases. OXA-146 also binds and hydrolyzes aztreonam, cefotaxime, ceftriaxone,
      and ampicillin with higher efficiency than OXA-23 and preserves activity against
      doripenem. In this study, we report the X-ray crystal structures of both the OXA
      23 and OXA-146 enzymes at 1.6-A and 1.2-A resolution. A comparison of the two
      structures shows that the extra alanine moves a methionine (M221) out of its
      normal position, where it forms a bridge over the top of the active site. This
      single amino acid insertion also lengthens the beta5-beta6 loop, moving the
      entire backbone of this region further away from the active site. A model of
      ceftazidime bound in the active site reveals that these two structural
      alterations are both likely to relieve steric clashes between the bulky R1 side
      chain of ceftazidime and OXA-23. With activity against all four classes of beta
      lactam antibiotics, OXA-146 represents an alarming new threat to the treatment of
      infections caused by Acinetobacter spp. 

PMID- 23877678
TI  - Effect of pulmonary surfactant on antimicrobial activity in vitro.
AB  - Time-kill curve experiments were performed with linezolid, doripenem,
      tigecycline, moxifloxacin, and daptomycin against Staphylococcus aureus and with
      colistin, moxifloxacin, and doripenem against Pseudomonas aeruginosa to evaluate
      the effect of porcine pulmonary surfactant on antimicrobial activity. Pulmonary
      surfactant significantly impaired the activities of moxifloxacin and colistin.
      When antibiotics are being developed for respiratory tract infections, the method
      described here might be used to preliminarily quantify the effect of pulmonary
      surfactant on antimicrobial activity. 

PMID- 23877679
TI  - Improvement of the pharmacokinetics and in vivo antibacterial efficacy of a novel
      type IIa topoisomerase inhibitor by formulation in liposomes.
AB  - Several useful properties of liposome-based formulations of various existing
      antibacterial drugs have been reported. These properties include lower MICs,
      improved pharmacokinetics, lower toxicity, selective distribution to infected
      tissues, and enhanced in vivo efficacy. Here we report in vivo studies of a
      liposomal formulation of a member of a novel class of antibacterial type II
      topoisomerase inhibitors, others of which have progressed to early phases of
      clinical trials. The free (i.e., nonliposomal) compound has broad-spectrum MICs
      but suboptimal pharmacokinetics in rats and mice, characterized by a high volume
      of distribution and rapid clearance. The liposomal formulation of the compound
      had essentially unchanged MICs but greatly reduced volume of distribution and
      clearance in rats and mice. In an in vivo mouse model of Staphylococcus aureus
      infection of one thigh, the liposomal compound localized preferentially to the
      infected thigh, whereas the free compound showed no preference for the infected
      versus the uninfected thigh. Most importantly, the liposomal compound had
      enhanced efficacy at clearing the infection compared with the free compound.
      Delivery of this class of compounds as liposomal formulations may offer clinical
      advantages compared with free compounds. 

PMID- 23877680
TI  - Synchrotron X-ray fluorescence microscopy of gallium in bladder tissue following
      gallium maltolate administration during urinary tract infection.
AB  - A mouse model of cystitis caused by uropathogenic Escherichia coli was used to
      study the distribution of gallium in bladder tissue following oral administration
      of gallium maltolate during urinary tract infection. The median concentration of
      gallium in homogenized bladder tissue from infected mice was 1.93 MUg/g after
      daily administration of gallium maltolate for 5 days. Synchrotron X-ray
      fluorescence imaging and X-ray absorption spectroscopy of bladder sections
      confirmed that gallium arrived at the transitional epithelium, a potential site
      of uropathogenic E. coli infection. Gallium and iron were similarly but not
      identically distributed in the tissues, suggesting that at least some
      distribution mechanisms are not common between the two elements. The results of
      this study indicate that gallium maltolate may be a suitable candidate for
      further development as a novel antimicrobial therapy for urinary tract infections
      caused by uropathogenic E. coli. 

PMID- 23877681
TI  - Adjunctive N-acetyl-L-cysteine in treatment of murine pneumococcal meningitis.
AB  - Despite antibiotic therapy, acute and long-term complications are still frequent
      in pneumococcal meningitis. One important trigger of these complications is
      oxidative stress, and adjunctive antioxidant treatment with N-acetyl-l-cysteine
      was suggested to be protective in experimental pneumococcal meningitis. However,
      studies of effects on neurological long-term sequelae are limited. Here, we
      investigated the impact of adjunctive N-acetyl-l-cysteine on long-term
      neurological deficits in a mouse model of meningitis. C57BL/6 mice were
      intracisternally infected with Streptococcus pneumoniae. Eighteen hours after
      infection, mice were treated with a combination of ceftriaxone and placebo or
      ceftriaxone and N-acetyl-l-cysteine, respectively. Two weeks after infection,
      neurologic deficits were assessed using a clinical score, an open field test
      (explorative activity), a t-maze test (memory function), and auditory brain stem
      responses (hearing loss). Furthermore, cochlear histomorphological correlates of
      hearing loss were assessed. Adjunctive N-acetyl-l-cysteine reduced hearing loss
      after pneumococcal meningitis, but the effect was minor. There was no significant
      benefit of adjunctive N-acetyl-l-cysteine treatment in regard to other long-term
      complications of pneumococcal meningitis. Cochlear morphological correlates of
      meningitis-associated hearing loss were not reduced by adjunctive N-acetyl-l
      cysteine. In conclusion, adjunctive therapy with N-acetyl-l-cysteine at a dosage
      of 300 mg/kg of body weight intraperitoneally for 4 days reduced hearing loss but
      not other neurologic deficits after pneumococcal meningitis in mice. These
      results make a clinical therapeutic benefit of N-acetyl-l-cysteine in the
      treatment of patients with pneumococcal meningitis questionable. 

PMID- 23877682
TI  - Effect of nitroxides on swarming motility and biofilm formation, multicellular
      behaviors in Pseudomonas aeruginosa.
AB  - The ability of nitric oxide (NO) to induce biofilm dispersion has been well
      established. Here, we investigated the effect of nitroxides (sterically hindered
      nitric oxide analogues) on biofilm formation and swarming motility in Pseudomonas
      aeruginosa. A transposon mutant unable to produce nitric oxide endogenously
      (nirS) was deficient in swarming motility relative to the wild type and the
      complemented strain. Moreover, expression of the nirS gene was upregulated by
      9.65-fold in wild-type swarming cells compared to planktonic cells. Wild-type
      swarming levels were substantially restored upon the exogenous addition of
      nitroxide containing compounds, a finding consistent with the hypothesis that NO
      is necessary for swarming motility. Here, we showed that nitroxides not only
      mimicked the dispersal activity of NO but also prevented biofilms from forming in
      flow cell chambers. In addition, a nirS transposon mutant was deficient in
      biofilm formation relative to the wild type and the complemented strain, thus
      implicating NO in the formation of biofilms. Intriguingly, despite its stand
      alone action in inhibiting biofilm formation and promoting dispersal, a nitroxide
      partially restored the ability of a nirS mutant to form biofilms. 

PMID- 23877683
TI  - Head-to-head comparison of inhibitory and fungicidal activities of fluconazole,
      itraconazole, voriconazole, posaconazole, and isavuconazole against clinical
      isolates of Trichosporon asahii.
AB  - Treatment of disseminated Trichosporon infections still remains difficult.
      Amphotericin B frequently displays inadequate fungicidal activity and
      echinocandins have no meaningful antifungal effect against this genus. Triazoles
      are currently the drugs of choice for the treatment of Trichosporon infections.
      This study evaluates the inhibitory and fungicidal activities of five triazoles
      against 90 clinical isolates of Trichosporon asahii. MICs (MUg/ml) were
      determined according to Clinical and Laboratory Standards Institute microdilution
      method M27-A3 at 24 and 48 h using two endpoints, MIC-2 and MIC-0 (the lowest
      concentrations that inhibited ~50 and 100% of growth, respectively). Minimum
      fungicidal concentrations (MFCs; MUg/ml) were determined by seeding 100 MUl of
      all clear MIC wells (using an inoculum of 10(4) CFU/ml) onto Sabouraud dextrose
      agar. Time-kill curves were assayed against four clinical T. asahii isolates and
      the T. asahii ATCC 201110 strain. The MIC-2 (~50% reduction in turbidity compared
      to the growth control well)/MIC-0 (complete inhibition of growth)/MFC values that
      inhibited 90% of isolates at 48 h were, respectively, 8/32/64 MUg/ml for
      fluconazole, 1/2/8 MUg/ml for itraconazole, 0.12/0.5/2 MUg/ml for voriconazole,
      0.5/2/4 MUg/ml for posaconazole, and 0.25/1/4 MUg/ml for isavuconazole. The MIC-0
      endpoints yielded more consistent MIC results, which remained mostly unchanged
      when extending the incubation to 48 h (98 to 100% agreement with 24-h values) and
      are easier to interpret. Based on the time-kill experiments, none of the drugs
      reached the fungicidal endpoint (99.9% killing), killing activity being shown but
      at concentrations not reached in serum. Statistical analysis revealed that
      killing rates are dose and antifungal dependent. The lowest concentration at
      which killing activity begins was for voriconazole, and the highest was for
      fluconazole. These results suggest that azoles display fungistatic activity and
      lack fungicidal effect against T. asahii. By rank order, the most active triazole
      is voriconazole, followed by itraconazole ~ posaconazole ~ isavuconazole >
      fluconazole. 

PMID- 23877684
TI  - A cointegrate-like plasmid that facilitates dissemination by conjugation of the
      extended-spectrum beta-lactamase CTX-M-17.

PMID- 23877685
TI  - Combination of pantothenamides with vanin inhibitors as a novel antibiotic
      strategy against gram-positive bacteria.
AB  - The emergence of resistance against current antibiotics calls for the development
      of new compounds to treat infectious diseases. Synthetic pantothenamides are
      pantothenate analogs that possess broad-spectrum antibacterial activity in vitro
      in minimal media. Pantothenamides were shown to be substrates of the bacterial
      coenzyme A (CoA) biosynthetic pathway, causing cellular CoA depletion and
      interference with fatty acid synthesis. In spite of their potential use and
      selectivity for bacterial metabolic routes, these compounds have never made it to
      the clinic. In the present study, we show that pantothenamides are not active as
      antibiotics in the presence of serum, and we found that they were hydrolyzed by
      ubiquitous pantetheinases of the vanin family. To address this further, we
      synthesized a series of pantetheinase inhibitors based on a pantothenate scaffold
      that inhibited serum pantetheinase activity in the nanomolar range. Mass
      spectrometric analysis showed that addition of these pantetheinase inhibitors
      prevented hydrolysis of pantothenamides by serum. We found that combinations of
      these novel pantetheinase inhibitors and prototypic pantothenamides like N5-Pan
      and N7-Pan exerted antimicrobial activity in vitro, particularly against Gram
      positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis,
      Streptococcus pneumoniae, and Streptococcus pyogenes) even in the presence of
      serum. These results indicate that pantothenamides, when protected against
      degradation by host pantetheinases, are potentially useful antimicrobial agents. 

PMID- 23877686
TI  - Unique structural modifications are present in the lipopolysaccharide from
      colistin-resistant strains of Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a nosocomial opportunistic pathogen that can cause
      severe infections, including hospital-acquired pneumonia, wound infections, and
      sepsis. Multidrug-resistant (MDR) strains are prevalent, further complicating
      patient treatment. Due to the increase in MDR strains, the cationic antimicrobial
      peptide colistin has been used to treat A. baumannii infections. Colistin
      resistant strains of A. baumannii with alterations to the lipid A component of
      lipopolysaccharide (LPS) have been reported; specifically, the lipid A structure
      was shown to be hepta-acylated with a phosphoethanolamine (pEtN) modification
      present on one of the terminal phosphate residues. Using a tandem mass
      spectrometry platform, we provide definitive evidence that the lipid A isolated
      from colistin-resistant A. baumannii MAC204 LPS contains a novel structure
      corresponding to a diphosphoryl hepta-acylated lipid A structure with both pEtN
      and galactosamine (GalN) modifications. To correlate our structural studies with
      clinically relevant samples, we characterized colistin-susceptible and -resistant
      isolates obtained from patients. These results demonstrated that the clinical
      colistin-resistant isolate had the same pEtN and GalN modifications as those seen
      in the laboratory-adapted A. baumannii strain MAC204. In summary, this work has
      shown complete structure characterization including the accurate assignment of
      acylation, phosphorylation, and glycosylation of lipid A from A. baumannii, which
      are important for resistance to colistin. 

PMID- 23877687
TI  - Appearance of macrolide-resistant Bordetella pertussis strains in China.

PMID- 23877688
TI  - Population pharmacokinetics study of recommended zidovudine doses in HIV-1
      infected children.
AB  - The aims of this study were to describe the pharmacokinetics of zidovudine (ZDV)
      and its biotransformation to its metabolite, 3*-azido-3*-deoxy-5*
      glucuronylthymidine (G-ZDV), in HIV-infected children, to identify factors that
      influence the pharmacokinetics of ZDV, and to compare and evaluate the doses
      recommended by the World Health Organization (WHO) and the Food and Drug
      Administration (FDA). ZDV concentrations in 782 samples and G-ZDV concentrations
      in 554 samples from 247 children ranging in age from 0.5 to 18 years were
      retrospectively measured. A population pharmacokinetic model was developed with
      NONMEM software (version 6.2), and the pharmacokinetics of ZDV were best
      described by a one-compartment model with first-order absorption and elimination.
      The effect of body weight on the apparent elimination clearance and volume of
      distribution was significant. The mean population parameter estimates were as
      follows: absorption rate, 2.86 h(-1); apparent elimination clearance, 89.7 liters
      . h(-1) (between-subject variability, 0.701 liters . h(-1)); apparent volume of
      distribution, 229 liters (between-subject variability, 0.807 liters); metabolic
      formation rate constant, 12.6 h(-1) (between-subject variability, 0.352 h(-1));
      and elimination rate constant of G-ZDV, 2.27 h(-1). On the basis of simulations
      with FDA and WHO dosing recommendations, the probabilities of observing efficient
      exposures (doses resulting in exposures of between 3 and 5 mg/liter . h) with
      less adverse events (doses resulting in exposures below 8.4 mg/liter . h) were
      higher when the FDA recommendations than when the WHO recommendations were
      followed. In order to improve the FDA recommendations, ZDV doses should be
      reconsidered for the weight band (WB) of 20 to 40 kg. The most appropriate doses
      should be decreased from 9 to 8 mg/kg of body weight twice a day (BID) for the WB
      from 20 to 29.9 kg and from 300 to 250 mg BID for the WB from 30 to 39.9 kg. The
      highest dose, 300 mg BID, should be started from body weights of 40 kg. 

PMID- 23877689
TI  - Pharmacokinetics and absorption of paromomycin and gentamicin from topical creams
      used to treat cutaneous leishmaniasis.
AB  - This study evaluated the pharmacokinetics of topical creams containing 15%
      paromomycin ("paromomycin alone") and 15% paromomycin plus 0.5% gentamicin (WR
      279,396) in patients with cutaneous leishmaniasis. The investigational creams
      were applied topically to all lesions once daily for 20 days. Plasma samples were
      analyzed for simultaneous quantitation of paromomycin and gentamicin isomers and
      total gentamicin. Pharmacokinetic parameters for gentamicin could not be
      calculated because detectable levels were rarely evident. After one application,
      the paromomycin area under the concentration-time curve from 0 to 24 h (AUC0-24)
      was 2,180 +/- 2,621 ng . h/ml (mean +/- standard deviation [SD]) for the
      paromomycin-alone group and 975.6 +/- 1,078 ng . h/ml for the WR 279,396 group.
      After 20 days of application, the paromomycin AUC0-24 and maximum concentration
      of drug (Cmax) were 5 to 6 times greater than those on day 1 for both treatment
      groups. For the paromomycin-alone group, the AUC0-24 was 8,575 +/- 7,268 ng .
      h/ml and the Cmax was 1,000 +/- 750 ng/ml, compared with 6,037 +/- 3,956 ng .
      h/ml and 660 +/- 486 ng/ml for the WR 279,396 group, respectively. Possibly due
      to large intersubject variability, no differences (P >= 0.05) in the AUC0-24 or
      Cmax were noted between treatment or between sites on day 1 or 20. The percentage
      of dose absorbed on day 20 was 12.0% +/- 6.26% and 9.68% +/- 6.05% for
      paromomycin alone and WR 279,396, respectively. Paromomycin concentrations in
      plasma after 20 days of application were 5 to 9% of those after intramuscular
      administration of 15 mg/kg of body weight/day to adults for the systemic
      treatment of visceral leishmaniasis. Effective topical treatment of cutaneous
      leishmaniasis appears to be possible with limited paromomycin and gentamicin
      systemic absorption, thus avoiding drug accumulation and toxicity. (The work
      described here has been registered at ClinicalTrials.gov under registration no.
      NCT01032382 and NCT01083576.).

PMID- 23877690
TI  - Modulation of biotransformation systems and ABC transporters by benznidazole in
      rats.
AB  - The effect of antichagasic benznidazole (BZL; 100 mg/kg body weight/day, 3
      consecutive days, intraperitoneally) on biotransformation systems and ABC
      transporters was evaluated in rats. Expression of cytochrome P-450 (CYP3A), UDP
      glucuronosyltransferase (UGT1A), glutathione S-transferases (alpha glutathione S
      transferase [GST-alpha], GST-MU, and GST-pi), multidrug-resistance-associated
      protein 2 (Mrp2), and P glycoprotein (P-gp) in liver, small intestine, and kidney
      was estimated by Western blotting. Increases in hepatic CYP3A (30%) and GST-MU
      (40%) and in intestinal GST-alpha (72% in jejunum and 136% in ileum) were
      detected. Significant increases in Mrp2 (300%) and P-gp (500%) proteins in liver
      from BZL-treated rats were observed without changes in kidney. P-gp and Mrp2 were
      also increased by BZL in jejunum (170% and 120%, respectively). In ileum, only P
      gp was increased by BZL (50%). The activities of GST, P-gp, and Mrp2 correlated
      well with the upregulation of proteins in liver and jejunum. Plasma decay of a
      test dose of BZL (5 mg/kg body weight) administered intraduodenally was faster
      (295%) and the area under the concentration-time curve (AUC) was lower (41%) for
      BZL-pretreated rats than for controls. The biliary excretion of BZL was higher
      (60%) in the BZL group, and urinary excretion of BZL did not show differences
      between groups. The amount of absorbed BZL in intestinal sacs was lower (25%) in
      pretreated rats than in controls. In conclusion, induction of biotransformation
      enzymes and/or transporters by BZL could increase the clearance and/or decrease
      the intestinal absorption of coadministered drugs that are substrates of these
      systems, including BZL itself. 

PMID- 23877691
TI  - Characterization of Hepatitis C virus resistance from a multiple-dose clinical
      trial of the novel NS5A inhibitor GS-5885.
AB  - GS-5885 is a novel hepatitis C virus (HCV) NS5A inhibitor. In a 3-day monotherapy
      study in treatment-naive genotype 1a (GT1a) and GT1b HCV-infected subjects,
      median viral load reductions ranged from 2.3 to 3.3 log10 HCV RNA IU/ml across
      dosing cohorts (1, 3, 10, 30, or 90 mg once daily). Here, we report viral
      sequencing and phenotypic analysis of clinical isolates from this study.
      Detection of baseline NS5A amino acid substitutions at positions 28, 30, 31, or
      93 in GT1a was associated with a reduced treatment response. In the GT1b cohort,
      Y93H was detected in 100% of subjects at day 4 or 14. In the Gt1a cohort,
      population sequencing detected NS5A resistance-associated mutations at day 4 or
      14 for 3/10 subjects at the 1-mg dose and for all subjects dosed at >=3 mg. A
      subset of mutants that confer a low level of reduced susceptibility to GS-5885
      was not detected by population sequencing at the 30- and 90-mg doses. Subject
      derived M28T, Q30R, L31M, and Y93C mutations all conferred >30-fold reductions in
      GS-5885 and daclatasvir susceptibilities in vitro. Site-directed NS5A mutants
      also showed reduced susceptibility to GS-5885. However, all NS5A mutants tested
      remained fully susceptible to other classes of direct-acting antivirals (DAAs),
      interferon alpha, and ribavirin. Importantly, the nonoverlapping resistance
      profile and high potency of GS-5885 support its further development with other
      direct-acting antivirals for the treatment of chronic HCV. (This study has been
      registered at ClinicalTrials.gov under registration number NCT01193478.). 

PMID- 23877692
TI  - Characterization of the new AmpC beta-lactamase FOX-8 reveals a single mutation,
      Phe313Leu, located in the R2 loop that affects ceftazidime hydrolysis.
AB  - A novel class C beta-lactamase (FOX-8) was isolated from a clinical strain of
      Escherichia coli. The FOX-8 enzyme possessed a unique substitution (Phe313Leu)
      compared to FOX-3. Isogenic E. coli strains carrying FOX-8 showed an 8-fold
      reduction in resistance to ceftazidime relative to FOX-3. In a kinetic analysis,
      FOX-8 displayed a 33-fold reduction in kcat/Km for ceftazidime compared to FOX-3.
      In the FOX family of beta-lactamases, the Phe313 residue located in the R2 loop
      affects ceftazidime hydrolysis and alters the phenotype of E. coli strains
      carrying this variant. 

PMID- 23877693
TI  - Mutation of RNA polymerase beta-subunit gene promotes heterogeneous-to
      homogeneous conversion of beta-lactam resistance in methicillin-resistant
      Staphylococcus aureus.
AB  - Three types of phenotypic expression of beta-lactam resistance have been reported
      in methicillin-resistant Staphylococcus aureus (MRSA): heterogeneous,
      homogeneous, and Eagle-type resistance. Heterogeneous-to-homogeneous conversion
      of beta-lactam resistance is postulated to be caused by a chromosomal mutation
      (chr*) in addition to the expression of the mecA gene. Eagle-type resistance is a
      unique phenotype of chr* occurring in pre-MRSA strain N315 whose mecA gene
      expression is strongly repressed by an intact mecI gene. We here report that
      certain mutations of the rpoB gene, encoding the RNA polymerase beta subunit,
      belong to chr*. We studied homogeneous MRSA (homo-MRSA) strain N315DeltaIP-H5
      (abbreviated as DeltaIP-H5), which was obtained from hetero-MRSA strain
      N315DeltaIP by selection with 8 mg/liter imipenem. Whole-genome sequencing of
      DeltaIP-H5 revealed the presence of a unique mutation in the rpoB gene,
      rpoB(N967I), causing the amino acid replacement of Asn by Ile at position 967 of
      RpoB. The effect of the rpoB(N967I) mutation was confirmed by constructing a
      revertant H5 rpoB(I967N) strain as well as an N315-derived mutant, N315
      rpoB(N967I). H5 rpoB(I967N) regained the hetero-resistance phenotype, and the
      N315 rpoB(N967I) strain showed an Eagle-type phenotype similar to that of the
      typical Eagle-type MRSA strain N315h4. Furthermore, subsequent whole-genome
      sequencing revealed that N315h4 also had a missense mutation of rpoB(R644H).
      Introduction of the rpoB(N967I) mutation was accompanied by decreased autolysis,
      prolonged doubling time, and tolerance to bactericidal concentrations of
      methicillin. We consider that rpoB mutations are the major cause for
      heterogeneous-to-homogeneous phenotypic conversion of beta-lactam resistance in
      MRSA strain N315 and its derived strains. 

PMID- 23877694
TI  - Globally expanding carbapenemase finally appears in Spain: nosocomial outbreak of
      acinetobacter baumannii producing plasmid-encoded OXA-23 in Barcelona, Spain.
AB  - Resistance of Acinetobacter baumannii clinical isolates to carbapenems is on the
      rise worldwide mainly in association with the production of OXA-23. Until
      recently, however, OXA-23 was absent in Spain. In this work, we report the
      molecular characterization of a hospital outbreak of OXA-23-producing A.
      baumannii in Barcelona caused by a multidrug-resistant (MDR) clone belonging to
      international clone IC-II/sequence type ST85 between October 2010 and May 2011.
      blaOXA-23 was carried in a plasmid of 90 kb and located within the composite
      transposon Tn2006. 

PMID- 23877695
TI  - Susceptibility to alternative oral antimicrobial agents in relation to sequence
      type ST131 status and Coresistance phenotype among recent Escherichia coli
      isolates from U.S. veterans.
AB  - The rising prevalence of resistance to first-line antimicrobial agents in
      Escherichia coli, which has paralleled the emergence of E. coli sequence type
      ST131, has created a need for alternative oral options for use in treating
      outpatients with infections such as cystitis and chronic prostatitis.
      Accordingly, we determined susceptibility to six alternative oral agents
      (azithromycin, chloramphenicol, doxycycline, fosfomycin, minocycline, and
      rifampin) by Etest or disk diffusion for 120 recently obtained E. coli clinical
      isolates from Veterans Affairs Medical Centers across the United States. Isolates
      were randomly selected in three subgroups of 40 isolates each based on
      coresistance to fluoroquinolones with and without extended-spectrum
      cephalosporins (ESCs). Results were stratified according to trimethoprim
      sulfamethoxazole (TMP-SMZ) phenotype. Overall, the prevalence of susceptible (or
      susceptible plus intermediate) isolates varied by agent, with rifampin being
      lowest (0%), fosfomycin highest (98 to 99%), and others in the mid-range (37 to
      88%). Substantial proportions of isolates (15 to 27%) yielded intermediate
      results for azithromycin, chloramphenicol, doxycycline, and minocycline. Among
      isolates resistant (versus susceptible) to fluoroquinolones with or without ESCs,
      susceptibility to the above four agents declined significantly among non-ST131
      isolates but not ST131 isolates. In contrast, in the presence of resistance to
      TMP-SMZ, susceptibility to azithromycin, doxycycline, and minocycline was
      significantly reduced among both ST131 and non-ST131 isolates. These findings
      identify potential alternative oral agents for use with E. coli isolates
      resistant to fluoroquinolones, ESCs, and/or TMP-SMZ and suggest that
      determination of ST131 status could help guide initial antimicrobial selection,
      pending susceptibility results. 

PMID- 23877696
TI  - Genetic characterization and emergence of the metallo-beta-lactamase GIM-1 in
      Pseudomonas spp. and Enterobacteriaceae during a long-term outbreak.
AB  - Since the first isolation in 2002, the metallo-beta-lactamase GIM-1 has not been
      detected outside Germany. The data presented here, for 50 clinical blaGIM-1
      positive isolates, including Pseudomonas spp. and Enterobacteriaceae
      (Enterobacter cloacae, Klebsiella oxytoca, Serratia marcescens, Escherichia coli,
      and Citrobacter freundii), collected between 2007 and 2012 at the original site
      in an ongoing outbreak, demonstrate a diverse genetic background and
      dissemination of the gene conferring resistance to enteric bacteria. 

PMID- 23877698
TI  - Genomic characterization of ciprofloxacin resistance in a laboratory-derived
      mutant and a clinical isolate of Streptococcus pneumoniae.
AB  - The broad-spectrum fluoroquinolone ciprofloxacin is a bactericidal antibiotic
      targeting DNA topoisomerase IV and DNA gyrase encoded by the parC and gyrA genes.
      Resistance to ciprofloxacin in Streptococcus pneumoniae mainly occurs through the
      acquisition of mutations in the quinolone resistance-determining region (QRDR) of
      the ParC and GyrA targets. A role in low-level ciprofloxacin resistance has also
      been attributed to efflux systems. To look into ciprofloxacin resistance at a
      genome-wide scale and to discover additional mutations implicated in resistance,
      we performed whole-genome sequencing of an S. pneumoniae isolate selected for
      resistance to ciprofloxacin in vitro (128 MUg/ml) and of a clinical isolate
      displaying low-level ciprofloxacin resistance (2 MUg/ml). Gene disruption and DNA
      transformation experiments with PCR fragments harboring the mutations identified
      in the in vitro S. pneumoniae mutant revealed that resistance is mainly due to
      QRDR mutations in parC and gyrA and to the overexpression of the ABC transporters
      PatA and PatB. In contrast, no QRDR mutations were identified in the genome of
      the S. pneumoniae clinical isolate with low-level resistance to ciprofloxacin.
      Assays performed in the presence of the efflux pump inhibitor reserpine suggested
      that resistance is likely mediated by efflux. Interestingly, the genome sequence
      of this clinical isolate also revealed mutations in the coding region of patA and
      patB that we implicated in resistance. Finally, a mutation in the NAD(P)H
      dependent glycerol-3-phosphate dehydrogenase identified in the S. pneumoniae
      clinical strain was shown to protect against ciprofloxacin-mediated reactive
      oxygen species. 

PMID- 23877699
TI  - Identification of extended-spectrum-beta-lactamase-positive Klebsiella pneumoniae
      urinary tract isolates harboring KPC and CTX-M beta-lactamases in nonhospitalized
      patients.
AB  - Forty-seven extended-spectrum-beta-lactamase-positive Klebsiella pneumoniae
      urinary tract isolates from nonhospitalized patients were identified, and 79%
      harbored KPC and/or CTX-M beta-lactamases. Approximately 90% of the isolates were
      resistant to trimethoprim-sulfamethoxazole and levofloxacin, and 40% were
      resistant to a carbapenem, while 92% were susceptible to polymyxin B, 87% were
      susceptible to tigecycline, and 79% were susceptible to fosfomycin. Increased use
      of broader-spectrum antibiotics may help to prevent their dissemination and
      reduce the risk of progression to invasive disease. 

PMID- 23877697
TI  - Cyclic AMP effectors in African trypanosomes revealed by genome-scale RNA
      interference library screening for resistance to the phosphodiesterase inhibitor
      CpdA.
AB  - One of the most promising new targets for trypanocidal drugs to emerge in recent
      years is the cyclic AMP (cAMP) phosphodiesterase (PDE) activity encoded by
      TbrPDEB1 and TbrPDEB2. These genes were genetically confirmed as essential, and a
      high-affinity inhibitor, CpdA, displays potent antitrypanosomal activity. To
      identify effectors of the elevated cAMP levels resulting from CpdA action and,
      consequently, potential sites for adaptations giving resistance to PDE
      inhibitors, resistance to the drug was induced. Selection of mutagenized
      trypanosomes resulted in resistance to CpdA as well as cross-resistance to
      membrane-permeable cAMP analogues but not to currently used trypanocidal drugs.
      Resistance was not due to changes in cAMP levels or in PDEB genes. A second
      approach, a genome-wide RNA interference (RNAi) library screen, returned four
      genes giving resistance to CpdA upon knockdown. Validation by independent RNAi
      strategies confirmed resistance to CpdA and suggested a role for the identified
      cAMP Response Proteins (CARPs) in cAMP action. CARP1 is unique to kinetoplastid
      parasites and has predicted cyclic nucleotide binding-like domains, and RNAi
      repression resulted in >100-fold resistance. CARP2 and CARP4 are hypothetical
      conserved proteins associated with the eukaryotic flagellar proteome or with
      flagellar function, with an orthologue of CARP4 implicated in human disease.
      CARP3 is a hypothetical protein, unique to Trypanosoma. CARP1 to CARP4 likely
      represent components of a novel cAMP signaling pathway in the parasite. As cAMP
      metabolism is validated as a drug target in Trypanosoma brucei, cAMP effectors
      highly divergent from the mammalian host, such as CARP1, lend themselves to
      further pharmacological development. 

PMID- 23877700
TI  - Comparative in vitro activities of SMT19969, a new antimicrobial agent, against
      Clostridium difficile and 350 gram-positive and gram-negative aerobic and
      anaerobic intestinal flora isolates.
AB  - The comparative in vitro activity of SMT19969, a novel, narrow-spectrum,
      nonabsorbable agent, was studied against 50 ribotype-defined Clostridium
      difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes,
      and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C.
      difficile isolates (MIC range, 0.125 to 0.5 MUg/ml; MIC90, 0.25 MUg/ml),
      including ribotype 027 strains, than fidaxomicin (range, 0.06 to 1 MUg/ml; MIC90,
      0.5 MUg/ml) and two to six dilutions lower than either vancomycin or
      metronidazole. SMT19969 and fidaxomicin were generally less active against Gram
      negative anaerobes, especially the Bacteroides fragilis group species, than
      vancomycin and metronidazole, suggesting that SMT19969 has a lesser impact on the
      normal intestinal microbiota that maintain colonization resistance. SMT19969
      showed limited activity against other Gram-positive anaerobes, including
      Bifidobacteria species, Eggerthella lenta, Finegoldia magna, and
      Peptostreptococcus anaerobius, with MIC90s of >512, >512, 64, and 64 MUg/ml,
      respectively. Clostridium species showed various levels of susceptibility, with
      C. innocuum being susceptible (MIC90, 1 MUg/ml) and C. ramosum and C. perfringens
      being nonsusceptible (MIC90, >512 MUg/ml). Activity against Lactobacillus spp.
      (range, 0.06 to >512 MUg/ml; MIC90, >512 MUg/ml) was comparable to that of
      fidaxomicin and varied by species and strain. Gram-positive aerobic cocci
      (Staphylococcus aureus, Enterococcus faecalis, E. faecium, and streptococci)
      showed high SMT19969 MIC90 values (128 to >512 MUg/ml). 

PMID- 23877701
TI  - Inhibition of hepatitis C virus infection by DNA aptamer against envelope
      protein.
AB  - Hepatitis C virus (HCV) envelope protein (E1E2) is essential for virus binding to
      host cells. Aptamers have been demonstrated to have strong promising applications
      in drug development. In the current study, a cDNA fragment encoding the entire
      E1E2 gene of HCV was cloned. E1E2 protein was expressed and purified. Aptamers
      for E1E2 were selected by the method of selective evolution of ligands by
      exponential enrichment (SELEX), and the antiviral actions of the aptamers were
      examined. The mechanism of their antiviral activity was investigated. The data
      show that selected aptamers for E1E2 specifically recognize the recombinant E1E2
      protein and E1E2 protein from HCV-infected cells. CD81 protein blocks the binding
      of aptamer E1E2-6 to E1E2 protein. Aptamers against E1E2 inhibit HCV infection in
      an infectious cell culture system although they have no effect on HCV replication
      in a replicon cell line. Beta interferon (IFN-beta) and IFN-stimulated genes
      (ISGs) are not induced in virus-infected hepatocytes with aptamer treatment,
      suggesting that E1E2-specific aptamers do not induce innate immunity. E2 protein
      is essential for the inhibition of HCV infection by aptamer E1E2-6, and the
      aptamer binding sites are located in E2. Q412R within E1E2 is the major
      resistance substitution identified. The data indicate that an aptamer against
      E1E2 exerts its antiviral effects through inhibition of virus binding to host
      cells. Aptamers against E1E2 can be used with envelope protein to understand the
      mechanisms of HCV entry and fusion. The aptamers may hold promise for development
      as therapeutic drugs for hepatitis C patients. 

PMID- 23877702
TI  - Interaction of silver nanoparticles with serum proteins affects their
      antimicrobial activity in vivo.
AB  - The emergence of multidrug-resistant bacteria is a global threat for human
      society. There exist recorded data that silver was used as an antimicrobial agent
      by the ancient Greeks and Romans during the 8th century. Silver nanoparticles
      (AgNPs) are of potential interest because of their effective antibacterial and
      antiviral activities, with minimal cytotoxic effects on the cells. However, very
      few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In
      this study, we deciphered the importance of the chosen methods for synthesis and
      capping of AgNPs for their improved activity in vivo. The interaction of AgNPs
      with serum albumin has a significant effect on their antibacterial activity. It
      was observed that uncapped AgNPs exhibited no antibacterial activity in the
      presence of serum proteins, due to the interaction with bovine serum albumin
      (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs [with
      citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to
      minimized interactions with serum proteins. The damage in the bacterial membrane
      was assessed by flow cytometry, which also showed that only capped AgNPs
      exhibited antibacterial properties, even in the presence of BSA. In order to
      understand the in vivo relevance of the antibacterial activities of different
      AgNPs, a murine salmonellosis model was used. It was conclusively proved that
      AgNPs capped with citrate or PVP exhibited significant antibacterial activities
      in vivo against Salmonella infection compared to uncapped AgNPs. These results
      clearly demonstrate the importance of capping agents and the synthesis method for
      AgNPs in their use as antimicrobial agents for therapeutic purposes. 

PMID- 23877703
TI  - P2' benzene carboxylic acid moiety is associated with decrease in cellular
      uptake: evaluation of novel nonpeptidic HIV-1 protease inhibitors containing P2
      bis-tetrahydrofuran moiety.
AB  - GRL007 and GRL008, two structurally related nonpeptidic human immunodeficiency
      virus type 1 (HIV-1) protease inhibitors (PIs) containing 3(R),3a(S),6a(R)-bis
      tetrahydrofuranylurethane (bis-THF) as the P2 moiety and a sulfonamide isostere
      consisting of benzene carboxylic acid and benzene carboxamide as the P2' moiety,
      respectively, were evaluated for their antiviral activity and interactions with
      wild-type protease (PR(WT)). Both GRL007 (Ki of 12.7 pM with PR(WT)) and GRL008
      (Ki of 8.9 pM) inhibited PR(WT) with high potency in vitro. X-ray
      crystallographic analysis of PR(WT) in complex with GRL007 or GRL008 showed that
      the bis-THF moiety of both compounds has three direct polar contacts with the
      backbone amide nitrogen atoms of Asp29 and Asp30 of PR(WT). The P2' moiety of
      both compounds showed one direct contact with the backbone of Asp30' and a
      bridging polar contact with Gly48' through a water molecule. Cell-based antiviral
      assays showed that GRL007 was inactive (50% effective concentration [EC50] of >1
      MUM) while GRL008 was highly active (EC50 of 0.04 MUM) against wild-type HIV-1.
      High-performance liquid chromatography (HPLC)/mass spectrometry-based cellular
      uptake assays showed 8.1- and 84-fold higher intracellular concentrations of
      GRL008 than GRL007 in human MT-2 and MT-4 cell extracts, respectively. Thus,
      GRL007, in spite of its favorable enzyme-inhibitory activity and protease binding
      profile, exhibited a lack of antiviral activity in cell-based assays, most likely
      due to its compromised cellular uptake associated with its P2' benzene carboxylic
      acid moiety. The anti-HIV-1 potency, favorable toxicity, and binding profile of
      GRL008 suggest that further optimization of the P2' moiety may improve its
      antiretroviral features. 

PMID- 23877704
TI  - First report of an Enterobacter ludwigii isolate coharboring NDM-1 and OXA-48
      carbapenemases.

PMID- 23877705
TI  - Field-based flow cytometry for ex vivo characterization of Plasmodium vivax and
      P. falciparum antimalarial sensitivity.
AB  - Ex vivo antimalarial sensitivity testing in human malaria parasites has largely
      depended on microscopic determination of schizont maturation. While this
      microscopic method is sensitive, it suffers from poor precision and is laborious.
      The recent development of portable, low-cost cytometers has allowed us to develop
      and validate a simple, field-optimized protocol using SYBR green and
      dihydroethidium for the accurate and objective determination of antimalarial drug
      sensitivity in freshly isolated Plasmodium vivax and Plasmodium falciparum. 

PMID- 23877706
TI  - Viral resistance in hepatitis C virus genotype 1-infected patients receiving the
      NS3 protease inhibitor Faldaprevir (BI 201335) in a phase 1b multiple-rising-dose
      study.
AB  - Faldaprevir (BI 201335) is a selective NS3/4A protease inhibitor under
      development for the treatment of chronic hepatitis C virus (HCV) infection.
      NS3/4A genotyping and NS3 protease phenotyping analyses were performed to monitor
      the emergence of resistance in patients with HCV genotype 1 infection receiving
      faldaprevir alone or combined with pegylated interferon alfa 2a and ribavirin
      (PegIFN-RBV) during a phase 1b study. Among all baseline variants, a maximum 7
      fold reduction in in vitro sensitivity to faldaprevir was observed for a rare NS3
      (V/I)170T polymorphism. During faldaprevir monotherapy in treatment-naive
      patients, virologic breakthrough was common (77%, 20/26) and was associated with
      the emergence of resistance mutations predominantly carrying NS3 substitutions
      R155K in GT1a and D168V in GT1b. D168V conferred a greater reduction in
      faldaprevir sensitivity (1,800-fold) than R155K (330-fold); however, D168V was
      generally less fit than R155K in the absence of selective drug pressure.
      Treatment-experienced patients treated with faldaprevir-PegIFN-RBV triple therapy
      showed higher viral load reductions, lower rates of breakthrough (8%, 5/62), and
      less frequent emergence of resistance-associated variants compared with
      faldaprevir monotherapy. (This study has been registered at ClinicalTrials.gov
      under registration no. NCT00793793.). 

PMID- 23877707
TI  - A high risk of hospitalization following release from correctional facilities in
      Medicare beneficiaries: a retrospective matched cohort study, 2002 to 2010.
AB  - IMPORTANCE: Little is known about the risk of individuals who are released from
      correctional facilities, a time when there may be discontinuity in care.
      OBJECTIVE: To study the risk for hospitalizations among former inmates soon after
      their release from correctional facilities. DESIGN: Retrospective cohort study.
      PARTICIPANTS: Data from Medicare administrative claims for 110,419 fee-for
      service beneficiaries who were released from a correctional facility from 2002
      through 2010 and controls matched by age, sex, race, Medicare status, and
      residential zip code. MAIN OUTCOMES AND MEASURES: Hospitalization rates and
      specifically those for ambulatory care-sensitive conditions 7, 30, and 90 days
      after release. RESULTS: Of 110,419 released inmates, 1559 individuals (1.4%) were
      hospitalized within 7 days after release; 4285 individuals (3.9%) within 30 days;
      and 9196 (8.3%) within 90 days. The odds of hospitalization was higher for
      released inmates compared with those of matched controls (within 7 days: odds
      ratio [OR], 2.5 [95% CI, 2.3-2.8]; within 30 days: OR, 2.1 [95% CI, 2.0-2.2]; and
      within 90 days: OR, 1.8 [95% CI, 1.7-1.9]). Compared with matched controls,
      former inmates were more likely to be hospitalized for ambulatory care-sensitive
      conditions (within 7 days: OR, 1.7 [95% CI, 1.4-2.1]; within 30 days: OR, 1.6
      [95% CI, 1.5-1.8]; and within 90 days: OR, 1.6 [95% CI, 1.5-1.7]). CONCLUSIONS
      AND RELEVANCE: About 1 in 70 former inmates are hospitalized for an acute
      condition within 7 days of release, and 1 in 12 by 90 days, a rate much higher
      than in the general population.

PMID- 23877708
TI  - Detection of high-risk atherosclerotic plaques by magnetic resonance imaging.
AB  - The goal of coronary plaque burden assessment is to detect vulnerable or high
      risk atherosclerotic plaques that are prone to rupture and to stabilize them
      through pharmacologic and other types of interventions before the development of
      acute coronary syndrome. In this regard, a reliable, reproducible, and less
      invasive imaging modality capable of identifying plaque characteristics
      associated with plaque vulnerability would be immensely useful for evaluating
      plaque status and predicting future cardiovascular events. Recently, magnetic
      resonance imaging (MRI) has emerged as a novel modality for atherosclerotic
      plaque detection and characterization. This review will cover the developments in
      MRI for characterizing atherosclerosis in carotid and coronary arteries and its
      use in clinical diagnoses and longitudinal studies to understand the
      pathophysiology of atherosclerosis.

PMID- 23877709
TI  - Ischemic mitral regurgitation.
AB  - Chronic ischemic mitral regurgitation (IMR) is still a significant clinical
      problem. It is present in 10-20% of patients with coronary artery disease and is
      associated with a worse prognosis after myocardial infarction and subsequent
      revascularization. Currently, coronary artery bypass grafting combined with
      restrictive annuloplasty is the most commonly performed surgical procedure,
      although novel approaches have been used in limited numbers with varying degrees
      of success. The purpose of this review is to clarify the rationale for the
      surgical techniques applicable to IMR. In order to do so, the condition will be
      defined and the evolution of classic or traditional surgical approaches to
      repairing or replacing the mitral valve in the setting of IMR will be described.
      Finally, novel approaches to the repair of the ischemic mitral valve will be
      considered. 

PMID- 23877710
TI  - Lower serum albumin level is associated with higher fractional excretion of
      creatinine.
AB  - BACKGROUND: Creatinine clearance (Ccr) overestimates glomerular filtration rate
      (GFR) due to the tubular secretion of creatinine. It is known that fractional
      excretion of creatinine (FE-Cr) increases with decreasing GFR. Association of
      serum albumin level with the tubular secretion of creatinine was also reported
      previously. Alteration of FE-Cr may affect the performance of GFR estimating
      equations based on serum creatinine. Therefore, we analyzed the factors
      influencing FE-Cr and compared the performance of GFR equations in subjects
      stratified by serum albumin levels. METHODS: Seven hundred and fifty-seven
      Japanese subjects were included. GFR was measured by inulin renal clearance. GFR
      and Ccr were measured simultaneously. FE-Cr was calculated as the ratio of Ccr to
      GFR. Multivariate analysis was performed to evaluate the factors influencing FE
      Cr. Age, gender, GFR, body mass index (BMI), body weight, height and serum
      albumin level were analyzed as the parameters. Estimated GFR was calculated by
      Japanese GFR equations based on serum creatinine (Eq-cr), serum cystatin C (Eq
      cys) and 5 variables including serum albumin (Eq-5var). RESULTS: FE-Cr in
      subjects with serum albumin <3.0, 3.0-3.9 and >=4.0 g/dl were 1.63 +/- 0.48, 1.53
      +/- 0.55, and 1.40 +/- 0.36, respectively. FE-Cr in subjects with serum albumin
      <3.0 or 3.0-3.9 g/dl were significantly higher than the value in subjects with
      serum albumin >=4.0 g/dl. Multivariate analysis showed that GFR (p < 0.0001) and
      serum albumin level (p = 0.004) were independent parameters affecting FE-Cr.
      Biases of Eq-cr, Eq-cys and Eq-5var in subjects with serum albumin <3.0 g/dl were
      -9.5 +/- 17.5, -0.7 +/- 17.1 and -0.6 +/- 14.8 ml/min/1.73 m(2), respectively. Eq
      cr significantly overestimated GFR compared with Eq-cys or Eq-5var. Biases in
      subjects with serum albumin >=4.0 g/dl were 6.4 +/- 18.8, 2.0 +/- 18.1 and 3.0 +/
      18.3 ml/min/1.73 m(2), respectively. Eq-cr significantly underestimated GFR
      compared with Eq-cys or Eq-5var. CONCLUSION: GFR and serum albumin level were
      independent parameters affecting FE-Cr. Alteration of FE-Cr according to the
      serum albumin levels may be one of the reasons of the bias of GFR equation based
      on serum creatinine.

PMID- 23877711
TI  - Anti-proliferative effect of honokiol in oral squamous cancer through the
      regulation of specificity protein 1.
AB  - Honokiol (HK), a novel plant-derived natural product, is a physiologically
      activated compound with polyphenolic structure, and has been identified to
      function as an anticancer agent. It has been widely used in several diseases as a
      traditional medicine for a long time. We investigated whether HK could show
      anticancer effects on two oral squamous cell lines (OSCCs), HN-22 and HSC-4. We
      demonstrated that HK-treated cells showed dramatic reduction in cell growth and
      apoptotic cell morphologies. Intriguingly, the transcription factor specificity
      protein 1 (Sp1) was significantly inhibited by HK in a dose-dependent manner.
      Furthermore, we checked changes in cell cycle regulatory proteins and anti
      apoptotic proteins at the molecular level, which are known as Sp1 target genes.
      The important key regulators in the cell cycle such as p27 and p21 were up
      regulated by HK-mediated down-regulation of Sp1, whereas anti-apoptotic proteins
      including Mcl-1 and survivin were decreased, resulting in caspase-dependent
      apoptosis. Taken together, results from this study suggest that HK could modulate
      Sp1 transactivation and induce apoptotic cell death through the regulation of
      cell cycle and suppression of anti-apoptotic proteins. In addition, HK may be
      used in cancer prevention and therapies to improve the clinical outcome as an
      anticancer drug.

PMID- 23877712
TI  - Anti-Proteus activity of some South African medicinal plants: their potential for
      the prevention of rheumatoid arthritis.
AB  - A wide variety of herbal remedies are used in traditional African medicine to
      treat rheumatoid arthritis (RA) and inflammation. Thirty-four extracts from 13
      South African plant species with a history of ethnobotanical usage in the
      treatment of inflammation were investigated for their ability to control two
      microbial triggers for RA (Proteus mirabilis and Proteus vulgaris). Twenty-nine
      of the extracts (85.3 %) inhibited the growth of P. mirabilis and 23 of them
      tested (67.7 %) inhibited the growth of P. vulgaris. Methanol and water extracts
      of Carpobrotus edulis, Lippia javanica, Pelargonium viridflorum, Ptaeroxylon
      obliquum, Syzygium cordatum leaf and bark, Terminalia pruinoides, Terminalia
      sericea, Warburgia salutaris bark and an aqueous extract of W. salutaris leaf
      were effective Proteus inhibitors, with MIC values <2,000 MUg/ml. The most potent
      extracts were examined by Reverse phase high performance liquid chromatography
      and UV-Vis spectroscopy for the presence of resveratrol. Only extracts from T.
      pruinoides and T. sericea contained resveratrol, indicating that it was not
      responsible for the anti-Proteus properties reported here. All extracts with
      Proteus inhibitory activity were also either non-toxic, or of low toxicity in the
      Artemia nauplii bioassay. The low toxicity of these extracts and their inhibitory
      bioactivity against Proteus spp. indicate their potential for blocking the onset
      of rheumatoid arthritis. 

PMID- 23877713
TI  - Tracking the first two seconds: three stages of visual information processing?
AB  - We compared visual priming and comparison tasks to assess information processing
      of a stimulus during the first 2 s after its onset. In both tasks, a 13-ms prime
      was followed at varying SOAs by a 40-ms probe. In the priming task, observers
      identified the probe as rapidly and accurately as possible; in the comparison
      task, observers determined as rapidly and accurately as possible whether or not
      the probe and prime were identical. Priming effects attained a maximum at an SOA
      of 133 ms and then declined monotonically to zero by 700 ms, indicating reliance
      on relatively brief visuosensory (iconic) memory. In contrast, the comparison
      effects yielded a multiphasic function, showing a maximum at 0 ms followed by a
      minimum at 133 ms, followed in turn by a maximum at 240 ms and another minimum at
      720 ms, and finally a third maximum at 1,200 ms before declining thereafter. The
      results indicate three stages of prime processing that we take to correspond to
      iconic visible persistence, iconic informational persistence, and visual working
      memory, with the first two used in the priming task and all three in the
      comparison task. These stages are related to stages presumed to underlie stimulus
      processing in other tasks, such as those giving rise to the attentional blink. 

PMID- 23877715
TI  - Biochemical investigation of kraft lignin degradation by Pandoraea sp. B-6
      isolated from bamboo slips.
AB  - Kraft lignin (KL) is the major pollutant in black liquor. The bacterial strain
      Pandoraea sp. B-6 was able to degrade KL without any co-substrate under high
      alkaline conditions. At least 38.2 % of chemical oxygen demand and 41.6 % of
      color were removed in 7 days at concentrations from 1 to 6 g L(-1). The optimum
      pH for KL degradation was 10 and the optimum temperature was 30  degrees C. The
      greatest activities of 2,249.2 U L(-1) for manganese peroxidase and 1,120.6 U L(
      1) for laccase were detected on the third and fifth day at pH 10, respectively.
      Many small molecules, such as cinnamic acid, ferulic acid, 2-hydroxy benzyl
      alcohol, and vanillyl methyl ketone, were formed during the period of KL
      degradation based on GC-MS analysis. These results indicate that this strain has
      great potential for biotreatment of black liquor.

PMID- 23877716
TI  - Comment on Jugun et al.: The safety and efficacy of high-dose daptomycin combined
      with rifampicin for the treatment of Gram-positive osteoarticular infections.

PMID- 23877717
TI  - Influence of intra-operative parameters on postoperative early recovery of active
      knee flexion in posterior-stabilized total knee arthroplasty.
AB  - PURPOSE: Active knee flexion is more important for daily activities than passive
      knee flexion. The hypothesis is that the intra-operative parameters such as
      osteotomized bone thickness and soft tissue balance affect the postoperative
      active flexion angle in total knee arthroplasty (TKA). Therefore, we evaluate the
      influence of intra-operative parameters on postoperative early recovery of active
      flexion after posterior-stabilized (PS) TKA. METHODS: The subjects were 45
      osteoarthritic knees undergoing primary PS TKA with anterior-reference technique.
      Intra-operative soft tissue balance was measured using an offset type tensor, and
      each osteotomized bone thickness was also measured. Pre- and postoperative active
      knee flexion angles were measured using lateral radiographs. Liner regression
      analysis was used to determine the influence of these intra-operative parameters
      on postoperative active flexion angles or recovery of active flexion angles.
      RESULTS: Pre-operative flexion angle was positively correlated with postoperative
      flexion angle (R = 0.52, P = 0.0002). Postoperative flexion angle was negatively
      correlated with the osteotomized bone thickness of femoral medial posterior
      condyle (R = -0.37, P = 0.012), and femoral lateral posterior condyle (R = -0.36,
      P = 0.015). Recovery of flexion angle was slightly negatively correlated with gap
      difference calculated by subtracting joint gap at extension from that at flexion
      between osteotomized surfaces (R = -0.30, P = 0.046). CONCLUSIONS: The
      osteotomized bone thickness of the femoral posterior condyle is a significant
      independent factor of postoperative flexion angles. This indicates that the
      restoration of the posterior condyle offset may lead to larger postoperative
      active flexion angles in PS TKA.

PMID- 23877718
TI  - Expression of immunoglobulin receptors with distinctive features indicating
      antigen selection by marginal zone B cells from human spleen.
AB  - Marginal zone (MZ) B cells, identified as surface (s)IgM(high)sIgD(low)CD23(low/
      )CD21(+)CD38(-) B cells, were purified from human spleens, and the features of
      their V(D)J gene rearrangements were investigated and compared with those of
      germinal center (GC), follicular mantle (FM) and switched memory (SM) B cells.
      Most MZ B cells were CD27(+) and exhibited somatic hypermutations (SHM), although
      to a lower extent than SM B cells. Moreover, among MZ B-cell rearrangements,
      recurrent sequences were observed, some of which displayed intraclonal
      diversification. The same diversifying sequences were detected in very low
      numbers in GC and FM B cells and only when a highly sensitive, gene-specific
      polymerase chain reaction was used. This result indicates that MZ B cells could
      expand and diversify in situ and also suggested the presence of a number of
      activation-induced cytidine deaminase (AID)-expressing B cells in the MZ. The
      notion of antigen-driven expansion/selection in situ is further supported by the
      VH CDR3 features of MZ B cells with highly conserved amino acids at specific
      positions and by the finding of shared ("stereotyped") sequences in two different
      spleens. Collectively, the data are consistent with the notion that MZ B cells
      are a special subset selected by in situ antigenic stimuli. 

PMID- 23877719
TI  - Construction and characterization of an infectious cDNA clone of enterovirus type
      71 subgenotype C4.
AB  - Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth
      disease and induces fatal neurological complications. In recent years, this virus
      has become a major threat to public health in the Asia-Pacific region, while no
      effective antiviral therapies and vaccines are currently available. In this
      study, we constructed and characterized for the first time an infectious full
      length EV71 cDNA clone derived from the SHZH98 strain, which was the first
      subgenotype C4 strain isolated in China. Our data demonstrate that the rescued
      EV71 viruses exhibited growth kinetics in vitro and morphologies similar to those
      of the BrCr-TR strain and reached a maximum titer of 10(7.5) TCID50/ml. Although
      the rescued viruses were able to infect suckling mice, no typical symptoms of
      EV71 infection were observed for up to 18 days post-inoculation. Taken together
      our research provides an important tool to study the epidemic strains of EV71 in
      the Asia-Pacific region and promote the development of vaccines. 

PMID- 23877720
TI  - Characterization of an insect-specific flavivirus (OCFVPT) co-isolated from
      Ochlerotatus caspius collected in southern Portugal along with a putative new
      Negev-like virus.
AB  - We describe the isolation and characterization of an insect-specific flavivirus
      (ISF) from Ochlerotatus caspius (Pallas, 1771) mosquitoes collected in southern
      Portugal. The RNA genome of this virus, tentatively designated OCFVPT, for O.
      caspius flavivirus from Portugal, encodes a polyprotein showing all the features
      expected for a flavivirus. As frequently observed for ISF, the viral genomes
      seems to encode a putative Fairly Interesting Flavivirus ORF (FIFO)-like product,
      the synthesis of which would occur as a result of a -1 translation frameshift
      event. OCFVPT was isolated in the C6/36 Stegomyia albopicta (= Aedes albopictus)
      cell line where it replicates rapidly, but failed to replicate in Vero cells in
      common with other ISFs. Unlike some of the latter, however, the OCFVPT genome
      does not seem to be integrated in the mosquito cells we tested. Phylogenetic
      analyses based on partial ISF NS5 nucleotide sequences placed OCFVPT among
      recently published viral strains documented from mosquitoes collected in the
      Iberian Peninsula, while analyses of ORF/E/NS3/or NS5 amino acid sequences
      cluster OCFVPT with HANKV (Hanko virus), an ISF recently isolated from O. caspius
      mosquitoes collected in Finland. Taking into account the genetic relatedness with
      this virus, OCFVPT is not expected to be overtly cytopathic to C6/36 cells. The
      cytopathic effects associated with its presence in culture supernatants are
      postulated to be the result of the replication of a co-isolated putative new
      Negev-like virus. 

PMID- 23877721
TI  - Infection: Potential protective role of raised PSA in recurrent UTI.

PMID- 23877723
TI  - Transplantation: Urinary RNA test to predict kidney graft rejection.

PMID- 23877722
TI  - Management of combat-related urological trauma in the modern era.
AB  - Complex genitourinary injuries--associated with lower-extremity amputation as
      well as pelvic and abdominal wounding--have emerged as common occurrences in
      current military combat operations. The nature of combat injuries of the
      genitourinary tract is varied, as are the strategies used in their management.
      For example, 5% of all combat injuries include wounds of the urinary system or
      genitalia. For injuries that are predominantly penetrating in nature, immediate
      care requires the judicious preservation of viable tissue. Once the patient is
      stable, urethral, corporal and testicular lacerations are closed primarily,
      whereas soft tissue injuries are re-approximated in a delayed fashion. Negative
      pressure dressings have been a useful aid in wound management; wound coverage is
      most commonly completed with split-thickness skin grafts and local flaps. Complex
      penile and urethral reconstructions are often delayed so orthopaedic injuries can
      heal and the patient can manage activities of daily living. Final reconstruction
      requires a urologist with a full understanding of reconstructive techniques.

PMID- 23877724
TI  - Historical perspectives in the diagnosis and treatment of primary immune
      deficiencies.
AB  - The field of Primary Immune Deficiency Disorders (PIDD) has advanced rapidly over
      the past several years with over 200 different gene mutations defined. With the
      recent institution of newborn screening for T cell deficiencies in many states
      and earlier recognition of the signs and symptoms of patients with immune
      deficiency, it is now apparent that PIDD is not as "rare" as was originally
      thought several decades ago. With the earlier recognition of patients with
      recurrent infections and various immune perturbations, advancements in the
      treatment of these immune deficiency disorders have led to enhanced survival and
      quality of life. In this issue, the diagnosis of PIDD through laboratory testing
      and skin manifestations is reviewed. The more recently described cellular immune
      deficiencies, selective immune deficiencies, and advances in the use of bone
      marrow transplantation in the correction of some of these immune deficiencies are
      discussed. 

PMID- 23877725
TI  - Knee temperatures measured in vivo after arthroscopic ACL reconstruction followed
      by cryotherapy with gel-packs or computer controlled heat extraction.
AB  - PURPOSE: To obtain in vivo data about intra- and extra-articular knee
      temperatures to assess the effectiveness of two cryotherapeutic methods
      conventional cooling with gel-packs and computer controlled cryotherapy following
      anterior cruciate ligament (ACL) reconstructive surgery. METHODS: Twenty patients
      were arbitrarily assigned for cryotherapy after ACL reconstruction: 8 patients
      with frozen gel-packs and 12 patients with computer controlled cryotherapy with
      constant temperatures of the cooling liquid in the knee pads. The treatment was
      performed for 12 h. Temperatures were measured with two thermo sensors in
      catheters placed intraarticularly and subcutaneously, four sensors on the skin
      and one sensor under protective bandage, every second for 16 h after surgery.
      RESULTS: In the first 2 h of treatment, there were no significant differences
      (n.s.) between the groups in temperatures in the intracondylar notch. After 4 h
      of cryotherapy, the temperatures were significantly lower on the skin (24.6 +/-
      2.8 and 31.4 +/- 1.3  degrees C, p < 0.01) and in the subcutaneous tissue (28.6
      +/- 5.7 and 34.6 +/- 1.4  degrees C, p = 0.01), and the difference between the
      temperature in the intracondylar notch and the subcutaneous tissue was
      significantly greater (4.0 +/- 3.0 and 0.8 +/- 0.6  degrees C, p = 0.01) in the
      computer controlled cryotherapy group compared to the gel-pack group.
      CONCLUSIONS: The cooling effect of the arthroscopy irrigation fluid on the knee
      temperature is evident in the first 2 h of treatment. The energy extraction is
      significantly more effective and controllable by computer controlled cryotherapy
      than with frozen gel-packs. LEVEL OF EVIDENCE: Prospective comparative study,
      Level II.

PMID- 23877726
TI  - Cast immobilization does not confer additional functional benefits over immediate
      mobilization after trapeziectomy.

PMID- 23877727
TI  - The connective tissue and ligaments of the distal interphalangeal joint: a review
      and investigation using ultra-high field 16.4 Tesla magnetic resonance imaging.
AB  - This study reviews the literature on the anatomy of the connective tissues
      surrounding the distal interphalangeal joint and further characterizes the three
      dimensional relationships of these structures with ultra-high field magnetic
      resonance imaging. Ten cadaver fingers, fixed in a solution of 5% agar and 4%
      formalin, were imaged utilising an ultrashield 16.4 Tesla ultra-high field
      magnetic resonance imaging, yielding a total of 4000 images. Images were analysed
      using OsirixTM (version 5.5.1 32 bit edition) for three-dimensional
      reconstruction. We found numerous conflicting descriptions of the connective
      tissue structures around the distal interphalangeal joint. Based upon our
      literature review and imaging studies we have defined precisely Cleland's
      ligaments, the oblique proximal septum, Grayson's ligaments, the dorsal plate,
      and the interosseous ligaments of the distal interphalangeal joint. 

PMID- 23877728
TI  - Long-term function after pseudo-pollicization of the little finger.
AB  - This article presents a technique for facilitating use of pinch between the ring
      and little fingers for use in rare cases of congenital absence, or severe
      hypoplasia, of the thumb in which pollicization of the index finger is
      impossible, or not advised because the child is already pinching by scissor
      action between the ring and little fingers. The technique avoids drawing
      attention to the hand, as is the case after true pollicization of the little
      finger. The technique was used in five hands in five children. Three of the
      patients could only be followed for under 2 years. Two patients were available
      for longer follow-up of 6 years and 2 months and 3 years after surgery. The
      surgery was shown to facilitate opening of the web and pinch between the little
      and ring finger tips, and continues to be of functional value to the children as
      they grow. 

PMID- 23877729
TI  - Carpal tunnel syndrome due to palmaris profundus tendon.

PMID- 23877730
TI  - Cubital tunnel syndrome: a comparison of an endoscopic technique with a minimal
      invasive open technique.
AB  - Both open and endoscopic methods for ulnar nerve decompression have been
      described. The purpose of this study is to compare the 6-month results of a
      minimal invasive open technique with an endoscopic technique. We treated 60
      patients with unilateral ulnar neuropathy at the elbow, employing both
      techniques. Six months postoperative we found no differences in treatment effect
      on pain and disability scores between both groups, but both techniques resulted
      in an early postoperative relief of symptoms and good patient satisfaction. 

PMID- 23877731
TI  - Right ventricular and tricuspid valve remodeling after bidirectional
      cavopulmonary anastomosis.
AB  - BACKGROUND: There are few investigations of the changes in tricuspid valve (TV)
      and right ventricular (RV) morphology following bidirectional cavopulmonary
      anastomosis (BCPA). METHODS AND RESULTS: The 2-D echocardiograms of 35 children
      (male, n=23; female, n=12; median age, 6 months; range, 3-10 months) with
      hypoplastic left heart syndrome, 1 month before and after BCPA performed between
      2005 and 2011, were retrospectively reviewed. Patients who underwent TV repair at
      BCPA were excluded. From the 4-chamber view, the coaptation length, vena
      contracta width and RV end-diastolic area before and after BCPA were measured and
      indexed to surface area. The severity of tricuspid regurgitation was graded
      qualitatively. After BCPA, RV end-diastolic area decreased from 2,951 +/- 584 to
      2,580 +/- 591 mm(2)/m(2) (P<0.001). The coaptation length of the anterior leaflet
      (8.8 +/- 5.8 vs. 11.0 +/- 6.2 mm/m(2), P=0.0014) and of the septal leaflet (13.5
      +/- 5.3 vs. 15.8 +/- 5.4mm/m(2), P=0.0072) increased after BCPA. The vena
      contracta width decreased (5.8 +/- 4.9 vs. 4.3 +/- 4.2 mm/m(2), P=0.035),
      although there was no change in tricuspid regurgitation grade after BCPC (1.4 +/-
      0.7 vs. 1.4 +/- 0.9, P=0.234). CONCLUSIONS: In children with hypoplastic left
      heart syndrome after BCPA, the coaptation length of the anterior and septal
      leaflets of the TV improved concomitantly with vena contracta width and RV end
      diastolic area despite unchanged tricuspid regurgitation grade. This suggests
      that favorable RV and TV remodeling accompanies the reduction in RV volume load
      following BCPA. 

PMID- 23877732
TI  - Implantable loop recorder allows an etiologic diagnosis in one-third of patients.
      Results of the Spanish reveal registry.
AB  - BACKGROUND: The implantable loop recorder (ILR) is a useful tool for diagnosing
      paroxysmal conditions potentially related to arrhythmias. Most investigations
      have focused on selected clinical studies or high-volume centers. The aim of this
      study was to evaluate the indications and outcomes of the ILR in real clinical
      practice. METHODS AND RESULTS: This was a prospective, multicenter registry of
      patients undergoing ILR implantation for clinical indications (April 2006
      December 2008). Clinical characteristics (symptoms, arrhythmias, treatments) were
      recorded in a database. Follow-up data at 1 year or after the occurrence of the
      first episode were also recorded. Total enrollment: 743 patients (male, 413,
      55.6%; 64.9 +/- 16 years); 228 (30.7%) had structural heart disease (SHD), and
      183 (24.6%), bundle branch block (BBB). Recurrent syncope (76.4%) was the most
      common indication for implantation. Complete follow-up was obtained for 680
      patients (91.5%). Three hundred and twenty-five patients (48%) presented 414
      events, with a final diagnosis in 230 patients (70.8% of patients with events;
      33.1% of patients with follow-up). Syncope secondary to bradyarrhythmia was the
      most frequent diagnosis. Similar rates of final diagnoses were noted in subgroups
      of SHD, BBB and normal heart. Regarding the cause of implantation, higher event
      rates were registered among patients with recurrent syncope. CONCLUSIONS: One
      third of patients obtained a final diagnosis with the ILR, independent of the
      baseline characteristics. Only the cause of implantation provided different rates
      of final diagnosis. 

PMID- 23877733
TI  - Optimal strength and number of shocks at upper limit of vulnerability testing
      required to predict high defibrillation threshold without inducing ventricular
      fibrillation.
AB  - BACKGROUND: The upper limit of vulnerability (ULV) closely correlates with the
      defibrillation threshold (DFT). The aim of this study was to establish the
      optimal protocol for using the ULV test to predict high DFT (>20 J) without
      inducing ventricular fibrillation (VF). METHODS AND RESULTS: The 10-J and 15-J
      ULV test with 3 coupling intervals (-20, 0, and +20 ms to the peak of T-wave) and
      the DFT test were performed in 96 patients receiving implantable cardioverter
      defibrillator. ULV <= 10 J was confirmed in 47 (49%). ULV <= 15 J was confirmed
      in 70 (77%) of 91 patients (15-J ULV test could not be done in 5). The
      sensitivity and negative predictive value of both ULV >10 J and >15 J for
      predicting high DFT were 100%. The specificity and positive predictive value of
      ULV >15 J were higher than those for ULV >10 J (85% vs. 55%, 43% vs. 22%,
      respectively). The rate of VF inducibility for confirming ULV <= 15 J was lower
      than that for ULV <= 10 J (23% vs. 51%, P<0.0001). On analysis of single 15-J ULV
      test only at the peak of T-wave, VF was not induced in 79 of 91 patients, but 4
      of these had high DFT. CONCLUSIONS: The 15-J ULV test with 3 coupling intervals
      could correctly identify high-DFT patients and reduce the necessity for VF
      induction at defibrillator implantation. 

PMID- 23877734
TI  - Hwanggeumchal sorghum extract enhances BMP7 and GH signaling through the
      activation of Jak2/STAT5B in MC3T3-E1 osteoblastic cells.
AB  - Sorghum is a principal cereal food in a number of parts of the world and is
      critical in folk medicine in Asia and Africa. However, its effects on bone are
      unknown. Growth hormone (GH) is a regulator of bone growth and bone metabolism.
      GH activates several signaling pathways, including the Janus kinase (Jak)/signal
      transducer and activator of transcription (STAT) pathways, thereby regulating
      expression of genes, including insulin-like growth factor (IGF)-1. Bone
      morphogenetic proteins (BMPs) induce the differentiation of cells of the
      osteoblastic lineage, increasing the pool of IGF-1 target cells, the mature
      osteoblasts. In the present study, the effects of Hwanggeumchal sorghum extracts
      (HSE) on GH signaling via the Jak/STAT pathway in osteoblasts were investigated.
      HSE was not observed to be toxic to osteoblastic cells and increased the
      expression of BMP7 and GH-related proteins, including STAT5B, p-STAT5B, IGF-1
      receptor (IGF-1R), growth receptor hormone (GHR) and Jak2 in MC3T3-E1 cells. In
      addition, HSE increased BMP7 and GHR mRNA expression in MC3T3-E1 cells. The
      expression of HSE-induced BMP7 and GHR was inhibited by AG490, a Jak2 kinase
      inhibitor. The observations indicate that HSE-induced signaling is similar to GH
      signaling via the GHR-Jak2 signaling axis. Using small interference RNA (siRNA)
      analysis, STAT5B was found to play an essential role in HSE-induced BMP7 and GH
      signaling in MC3T3-E1 cells. Results of the current study indicate that HSE
      promotes bone growth through activation of STAT5B. 

PMID- 23877738
TI  - Navigating time and uncertainty in health technology appraisal: would a map help?
AB  - Healthcare systems are increasingly under pressure to provide funding for
      innovative technologies. These technologies tend to be characterized by their
      potential to make valued contributions to patient health in areas of relative
      unmet need, and have high acquisition costs and uncertainty within the evidence
      base on their actual impact on health. Decision makers are increasingly
      interested in linking reimbursement strategies to the degree of uncertainty in
      the evidence base and, as a result, reimbursement for innovative technologies is
      frequently linked to some form of patient access or risk-sharing scheme. As the
      dominant methods of economic evaluation report final outcomes only at the time
      horizon of the analysis, they present only aggregated information. This omits
      much of the information available on how net benefit is distributed within the
      time horizon. In this article, we introduce the Net Benefit Probability Map
      (NBPM), which maps net health benefit versus time to identify how certain
      decision makers can be about the benefit of technologies at multiple time points.
      Using an illustrative example, we show how the NBPM can inform decision makers
      about how long it will take for innovative technologies to 'pay off', how
      methodological choices on discount rates affect results and how alternative
      payment mechanisms can reduce the risk for decision makers facing innovative
      technologies. 

PMID- 23877740
TI  - Responses of state Medicaid programs to buprenorphine diversion: doing more harm
      than good?

PMID- 23877741
TI  - Antioxidant micronutrients and cardiovascular risk in patients with diabetes: a
      systematic review.
AB  - BACKGROUND: Inverse associations between micronutrient intake and cardiovascular
      outcomes have been previously shown, but did not focus on diabetic patients.
      OBJECTIVE: To systematically review the role of micronutrients in the
      development/presence of cardiovascular outcomes in patients with diabetes.
      METHODS: We searched Medline, Embase, and Scopus (January/1949-March/2012) for
      observational studies that evaluated micronutrients and cardiovascular outcomes
      in patients with diabetes, and then selected and extracted the data (two
      independent reviewers). RESULTS: From the 15 658 studies identified, five were
      included, comprising three case-control and two cohorts, with a follow-up of 7-15
      years. A meta-analysis was not performed due to the different antioxidant
      micronutrients (types and measurement methods) and outcomes evaluated. The
      micronutrients assessed were vitamin C intake in diet and/or supplementation,
      chromium and selenium in toenail samples, and alpha-tocopherol and zinc in serum
      levels. Intake of >300 mg of vitamin C through supplementation was associated
      with increased risk of cardiovascular disease, coronary artery disease (CAD), and
      stroke (RR 1.69-2.37). High levels of alpha-tocopherol in serum were associated
      with 30% lower CAD risk in another study (HR 0.71; 95%CI 0.53-0.94). Among
      minerals (zinc, selenium, and chromium), an inverse association between zinc and
      CAD was observed; levels lower than 14.1 umol/L were associated with an increased
      risk for CAD (RR 1.70; 95%CI 1.21-2.38). CONCLUSION: The information available on
      this issue is scarce. Further prospective studies are needed to elucidate the
      role of these nutrients in the cardiovascular risk of patients with diabetes.

PMID- 23877742
TI  - Catheter ablation of arrhythmias exclusively using electroanatomic mapping: a
      series of cases.
AB  - BACKGROUND: Catheter ablation is a treatment that can cure various cardiac
      arrhythmias. Fluoroscopy is used to locate and direct catheters to areas that
      cause arrhythmias. However, fluoroscopy has several risks. Electroanatomic
      mapping (EAM) facilitates three-dimensional imaging without X-rays, which reduces
      risks associated with fluoroscopy. OBJECTIVE: We describe a series of patient
      cases wherein cardiac arrhythmia ablation was exclusively performed using EAM.
      METHODS: Patients who presented with cardiac arrhythmias that were unresponsive
      to pharmacological therapy were prospectively selected between March 2011 and
      March 2012 for arrhythmia ablation exclusively through EAM. Patients with
      indications for a diagnostic electrophysiology study and ablation of atrial
      fibrillation, left atrial tachyarrhythmias as well as hemodynamically unstable
      ventricular arrhythmia were excluded. We documented the procedure time, success
      rate and complications as well as whether fluoroscopy was necessary during the
      procedure. RESULTS: In total, 11 patients were enrolled in the study, including
      seven female patients (63%). The mean age of the patients was 50 years (SD +/-
      16.5). Indications for the investigated procedures included four cases (35%) of
      atrial flutter, three cases (27%) of pre-excitation syndrome, two cases (19%) of
      paroxysmal supraventricular tachycardia and two cases (19%) of ventricular
      extrasystoles. The mean procedure duration was 86.6 min (SD +/- 26 min).
      Immediate success (at discharge) of the procedure was evident for nine patients
      (81%). There were no complications during the procedures. CONCLUSION: This study
      demonstrates the feasibility of performing an arrhythmia ablation exclusively
      using EAM with satisfactory results.

PMID- 23877743
TI  - Correlation between the intima-media thickness of the proximal and distal common
      carotids.
AB  - BACKGROUND: Increased IMT (intima-media thickness) in carotids is used as an
      early atherosclerosis marker and to evaluate the risk of cardiovascular problems.
      Ultrasound is used in the evaluation because it is accessible and low cost.
      Measurements for different carotid regions are described. OBJECTIVE: To compare
      the proximal and distal region IMTs for the bilateral common carotid and guide
      its use in clinical practice. METHODS: The IMT was measured in the proximal and
      distal common carotid arteries of 798 individuals (35-74 years old) of both
      genders using high-resolution ultrasound. Pearson's correlation coefficient was
      used to establish associations. The analyses were initially performed for the
      entire sample as well as subgroups with IMT < 0.90 mm (49% of the sample) and >=
      0.90 mm for at least one measurement site. The statistical significance was p <
      0.05. RESULTS: The correlations investigated were significant. In the group with
      an IMT < 0.90 mm, the correlations were between 0.44 and 0.62. In the subgroup
      with an IMT >= 0.90 mm, the correlations were significantly reduced to between
      0.20 and 0.40. CONCLUSION: The data suggest that the IMT is more uniform along
      the carotid during early development and tends develop focally as it progresses.
      Therefore, in clinical evaluations of patients, the common carotid length should
      be investigated bilaterally to better use the available software and discern the
      IMT.

PMID- 23877744
TI  - Etanercept induces low QRS voltage and autonomic dysfunction in mice with
      experimental Chagas disease.
AB  - BACKGROUND: Chagas disease is a tropical parasitic disease caused by the
      flagellate protozoan Trypanosoma cruzi. Chagasic cardiomyopathy is characterized
      by disorders of autonomic regulation and action potential conduction in the acute
      and chronic phases of infection. Although tumor necrosis factor alpha (TNF-alpha)
      has been linked to cardiomyopathy in experimental models and in patients with
      Chagas disease, other reports suggest that TNF-alpha may exert anti-parasitic
      actions during the acute phase of infection. OBJECTIVES: This study aimed to
      determine the effects of a soluble TNF-alpha agonist, etanercept, on
      electrocardiographic parameters in the acute phase of experimental infection with
      Trypanosoma cruzi. METHODS: Electrocardiograms were obtained from untreated
      infected mice and infected mice who were treated with etanercept 7 days after
      infection. ECG wave and heart rate variability parameters were determined using
      Chart for Windows. RESULTS: Etanercept treatment resulted in a low QRS voltage
      and decreased heart rate variability compared with no treatment. However, the
      treated mice exhibited a delay in the fall of the survival curve during the acute
      phase. CONCLUSION: The results of this study suggest that although etanercept
      treatment promotes survival in mice infected with a virulent T. cruzi strain, TNF
      alpha blockade generates a low voltage complex and autonomic dysfunction during
      the acute phase of infection. These findings indicate that mortality during the
      acute phase can be attributed to a systemic inflammatory response rather than
      cardiac dysfunction.

PMID- 23877745
TI  - Assessment of the adherence of cardiologists to guidelines for the treatment of
      atrial fibrillation.
AB  - BACKGROUND: No local studies evaluating the knowledge of cardiologists on the
      management of atrial fibrillation (AF) and their adherence to these guidelines
      are available. OBJECTIVE: To evaluate the knowledge of cardiologists on the
      guidelines and clinical practices for the treatment of AF, correlating it to the
      time since medical graduation. METHODS: Cross-sectional study randomly including
      cardiologists affiliated to the Society of Cardiology of the State of Rio Grande
      do Sul (Sociedade de Cardiologia do Estado do Rio Grande do Sul - SOCERGS). The
      physicians were divided into two groups, according to time since graduation:
      those graduated for more (G1) or less (G2) than 25 years. RESULTS: Of the 859
      SOCERGS members, 150 were interviewed, and six refused to participate in the
      study. G1 comprised 71 physicians, and G2, 73. Differences were observed in
      regard to the following variables: use of betablockers as the first-choice drug
      for the control of AF response in 59.2% (G1) vs 91.8% (G2) (p<0.0001); use of
      digoxin as the preferred drug for the control of AF response in 19.7% (G1) vs 0%
      (G2) (p< 0.0001); warfarin as the preferred anticoagulant in 71.8% (G1) vs 93.2%
      (G2) (p=0.009); application of a risk score for anticoagulation in 73.2% (G1) vs
      87.7% (G2) (p=0.02). In questions regarding the knowledge about the Brazilian
      Society of Cardiology's guideline for AF, the overall percentage of right answers
      was 82.3%. CONCLUSION: Most of the clinical measures regarding the management of
      AF comply with the guidelines, and the clinical practice differs according with
      the time since graduation.

PMID- 23877747
TI  - Lycium barbarum polysaccharides protect rat liver from non-alcoholic
      steatohepatitis-induced injury.
AB  - BACKGROUND: Lycium barbarum polysaccharides (LBPs) are antioxidant and
      neuroprotective derivative from Wolfberry. However, whether LBP has a protective
      effect in non-alcoholic steatohepatitis (NASH)-induced hepatic injury is still
      unknown. OBJECTIVE: We aimed to study the possible hepatoprotective effects and
      mechanisms of LBP on a diet-induced NASH rat model. METHODS AND DESIGN: In this
      study, female rats were fed a high-fat diet to induce NASH with or without an
      oral 1 mg kg(-1) LBP feeding daily for 8 weeks. After 8 weeks, blood serum and
      liver samples from each rat were subjected to histological analysis, biochemical
      and molecular measurements. RESULTS: Compared with control rats, NASH rats showed
      typical NASH features including an increase in liver injury, lipid content,
      fibrosis, oxidative stress, inflammation and apoptosis. In contrast, NASH+LBP-co
      treated rats showed (1) improved histology and free fatty acid levels; (2) re
      balance of lipid metabolism; (3) reduction in profibrogenic factors through the
      TGF-beta/SMAD pathway; (4) improved oxidative stress through cytochrome P450 2E1
      dependent pathway; (5) reduction in hepatic pro-inflammatory mediators and
      chemokines production; and (6) amelioration of hepatic apoptosis through the p53
      dependent intrinsic and extrinsic pathways. The preventive effects of LBP were
      partly modulated through the PI3K/Akt/FoxO1, LKB1/AMPK, JNK/c-Jun and MEK/ERK
      pathways and the downregulation of transcription factors in the liver, such as
      nuclear factor-kappaB and activator protein-1. CONCLUSION: LBP is a novel
      hepatoprotective agent against NASH caused by abnormal liver metabolic functions.

PMID- 23877748
TI  - Cloning and characterization of two allelic glyceraldehyde-3-phosphate
      dehydrogenase genes in Auricularia auricula-judae.
AB  - Two allelic variants of the gpd gene, Gpd(a) and Gpd(b), were isolated based on a
      putative glyceraldehyde-3-phosphate dehydrogenase encoding sequence from the
      transcriptome of Auricularia auricula-judae strain Au916. The two alleles were
      found to have a 73 bp length discrepancy and 39 SNP variations. Both of the
      genomic DNA sequences of two alleles were interrupted by five introns, and
      encoded a same 340 aa protein. Intron positions analysis showed that the first
      intron was absent, but the last unique intron was gained in A. auricula-judae.
      Allele-specific expression analysis showed that the Gpd(a) and Gpd(b) were
      expressed with no significant difference in dikaryotic mycelia of A. auricula
      judae. To the best of our knowledge, this is the first report about the detection
      of two allelic gpd genes in A. auricula-judae, as well as the application of
      allele-specific primers in gene expression analysis for this edible fungus.

PMID- 23877749
TI  - Gaze response to dyadic bids at 2 years related to outcomes at 3 years in autism
      spectrum disorders: a subtyping analysis.
AB  - Variability in attention towards direct gaze and child-directed speech may
      contribute to heterogeneity of clinical presentation in toddlers with autism
      spectrum disorders (ASD). To evaluate this hypothesis, we clustered sixty-five 20
      month-old toddlers with ASD based on their visual responses to dyadic cues for
      engagement, identifying three subgroups. Subsequently, we compared social,
      language, and adaptive functioning of these subgroups at 3 years of age. The
      cluster displaying limited attention to social scenes in general exhibited poor
      outcome at 3 years; the cluster displaying good attention to the scene and to the
      speaker's mouth was verbal and high functioning at 3 years. Analysis of visual
      responses to dyadic cues may provide a clinically meaningful approach to
      identifying early predictors of outcome. 

PMID- 23877750
TI  - The personal impact of pelvic floor symptoms and their relationship to age.
AB  - INTRODUCTION AND HYPOTHESIS: The aim was to evaluate the relationship between age
      and the impact of pelvic floor disorders (PFD) using a multi-dimensional pelvic
      floor questionnaire METHODS: Questionnaire data on 4,311 women attending
      urogynaecology clinics with PFD were stratified by age into four groups: <=35, 36
      50, 51-65 and >65 years. The symptom frequency (ranging from 0 to 100) was
      divided in to mild (0-33), moderate (34-67), and severe (68-100) symptoms. Impact
      scores for equivalent levels of symptom frequency (mild, moderate and severe
      symptoms) were compared in women of different ages. RESULTS: Overall, bowel
      continence was associated with the greatest bother and constipation the least.
      Older women were significantly less bothered by mild to moderate urinary, bowel
      and vaginal symptoms (except IBS and vaginal capacity) than younger women. There
      was no difference in the impact of severe symptoms in different ages. In
      contrast, for sexual symptoms, there was a significant difference in the impact
      in older women for all grades of severity. CONCLUSIONS: Women's views and
      attitudes towards symptoms are variable and age is a significant factor. In women
      attending urogynaecology clinics with pelvic floor symptoms the impact of most
      symptoms (particularly sexual dysfunction) become less bothersome with age.

PMID- 23877752
TI  - Relationship between severity of footpad dermatitis and carcass performance in
      broiler chickens.
AB  - The relationship between the severity of footpad dermatitis (FPD) and growth
      performance parameters (live weight, condemnation rate, leg meat yield and breast
      meat yield) was investigated in a total of 63 million broiler chickens that were
      processed over a period of 1,053 days between 2008 and 2012 at a full-scale
      processing plant in Kagoshima Prefecture, Japan. FPD scores and carcass data were
      summarized daily and analyzed to determine their correlations. It was found that
      FPD severity was positively correlated with the condemnation rate and negatively
      correlated with the live weight and leg meat yield. These results indicate that
      controlling FPD may play an important role in reducing condemnations while
      improving live weight and leg meat yields. 

PMID- 23877751
TI  - Human proangiogenic circulating hematopoietic stem and progenitor cells promote
      tumor growth in an orthotopic melanoma xenograft model.
AB  - We previously identified a distinct population of human circulating hematopoietic
      stem and progenitor cells (CHSPCs; CD14(-)glyA(-)CD34(+)AC133(+/
      )CD45(dim)CD31(+) cells) in the peripheral blood (PB) and bone marrow, and their
      frequency in the PB can correlate with disease state. The proangiogenic subset
      (pCHSPC) play a role in regulating tumor progression, for we previously
      demonstrated a statistically significant increase in C32 melanoma growth in
      NOD.Cg-Prkdc (scid) (NOD/SCID) injected with human pCHSPCs (p < 0.001). We now
      provide further evidence that pCHSPCs possess proangiogenic properties. In vitro
      bio-plex cytokine analyses and tube forming assays indicate that pCHSPCs secrete
      a proangiogenic profile and promote vessel formation respectively. We also
      developed a humanized bone marrow-melanoma orthotopic model to explore in vivo
      the biological significance of the pCHSPC population. Growth of melanoma
      xenografts increased more rapidly at 3-4 weeks post-tumor implantation in mice
      previously transplanted with human CD34(+) cells compared to control mice.
      Increases in pCHSPCs in PB correlated with increases in tumor growth.
      Additionally, to determine if we could prevent the appearance of pCHSPCs in the
      PB, mice with humanized bone marrow-melanoma xenografts were administered
      Interferon alpha-2b, which is used clinically for treatment of melanoma. The
      mobilization of the pCHSPCs was decreased in the mice with the humanized bone
      marrow-melanoma xenografts. Taken together, these data indicate that pCHSPCs play
      a functional role in tumor growth. The novel in vivo model described here can be
      utilized to further validate pCHSPCs as a biomarker of tumor progression. The
      model can also be used to screen and optimize anticancer/anti-angiogenic
      therapies in a humanized system.

PMID- 23877753
TI  - Coverage of skin defects without skin grafts using adipose-derived stem cells.
AB  - A satisfying result is difficult to achieve in the repair of a full-thickness
      skin defect in the facial area, including the subunits of the nose. A full
      thickness skin graft, nasolabial flap, or forehead flap as a major treatment
      still is used despite its relative potential for secondary contracture, unmatched
      skin color, hypertrophic scars, and donor-site morbidity. Another option, with
      good wound-healing power and soft tissue regeneration without skin grafts would
      be helpful for initiating treatment. Adult stem cells are a useful material in
      tissue engineering. Adipose-derived stem cells (ADSCs), an abundant population of
      pluripotent cells found in the stroma of adipose tissues, have been shown to
      differentiate in vitro into various cell lineages. As a robust source of
      bioactive growth factors, ADSCs contribute to recovery from ischemic damage, and
      they can promote the wound-healing process as well as soft tissue regeneration.
      The authors have experienced several cases of facial skin defect repair using
      ADSCs without skin grafts. In these cases, they observed rapid coverage of the
      wound with the patient's own regenerated tissue. During the treatment period,
      ADSC treatment showed an excellent wound-healing process in terms of quantity and
      quality.

PMID- 23877754
TI  - Endoscopic reconstruction of partial mastectomy defects using latissimus dorsi
      muscle flap without causing scars on the back.
AB  - BACKGROUND: Results obtained with breast-conserving therapy are not always
      satisfactory. Reconstruction with a pure latissimus dorsi muscle flap is a useful
      option. The techniques described for endoscopic dissection of the flap create
      several scars on the back. As a result, they do not improve on the open approach,
      which causes a horizontal scar at the level of the bra strap. The authors'
      technique avoids all scars on the back using a single incision in the highest
      folds of the axilla, which also is used for the sentinel node biopsy or
      lymphadectomy and quadrantectomy. METHODS: The study was performed with 23
      patients. The tumor was extracted via a clockwise downward periareolar incision
      and via another incision in a fold of the axilla. Through this axillary incision,
      the sentinel lymph node biopsy or lymphadectomy was performed, and the external
      part of the latissimus dorsi muscle was harvested endoscopically for the
      reconstruction. RESULTS: Both the medical team and the patients reported high
      satisfaction with the aesthetic and functional results due to the preservation of
      the breast shape and the absence of any scarring on the back. CONCLUSION:
      Endoscopy-assisted techniques make either three small scars on the back or one
      long scar, with the muscle sectioned distally, or a vertical incision in the
      midaxillary line, which may form a hypertrophic or keloid scar. The authors'
      approach avoids the creation of these scars on the back because the endoscopy and
      the distal sectioning of the muscle flap are performed through the single
      axillary incision.

PMID- 23877755
TI  - Silencing of desmoplakin decreases connexin43/Nav1.5 expression and sodium
      current in HL-1 cardiomyocytes.
AB  - Desmosomes and gap junctions are situated in the intercalated disks of cardiac
      muscle and maintain the integrity of mechanical coupling and electrical impulse
      conduction between cells. The desmosomal plakin protein, desmoplakin (DSP), also
      plays a crucial role in the stability of these interconnected components as well
      as gap junction connexin proteins. In addition to cell-to-cell junctions, other
      molecules, including voltage-gated sodium channels (Nav1.5) are present in the
      intercalated disk and support the contraction of cardiac muscle. Mutations in
      genes encoding desmosome proteins may result in fatal arrhythmias, including
      arrhythmogenic right ventricular cardiomyopathy (ARVC). Therefore, the aim of the
      present study was to determine whether the presence of DSP is necessary for the
      normal function and localization of gap junction protein connexin43 (Cx43) and
      Nav1.5. To examine this hypothesis, RNA interference was utilized to knock down
      the expression of DSP in HL-1 cells and the content, distribution and function of
      Cx43 and Nav1.5 was assessed. Western blotting and flow cytometry experiments
      revealed that Cx43 and Nav1.5 expression decreased following DSP silencing. In
      addition, immunofluorescence studies demonstrated that a loss of DSP expression
      led to an abnormal distribution of Cx43 and Nav1.5, while scrape-loading
      dye/transfer revealed a decrease in dye transfer in DSP siRNA-treated cells. The
      sodium current was also recorded by the whole-cell patch clamp technique. The
      results indicated that DSP suppression decreased sodium current and slowed
      conduction velocity in cultured cells. The present study indicates that impaired
      mechanical coupling largely affects electrical synchrony, further uncovering the
      pathogenesis of ARVC.

PMID- 23877758
TI  - Clinical value of surveillance pouchoscopy in asymptomatic ileal pouch patients
      with underlying inflammatory bowel disease.
AB  - BACKGROUND: There is no consensus on the need for and the interval of
      surveillance pouchoscopy in asymptomatic ileal pouch patients with underlying
      ulcerative colitis (UC). The purpose of this study was to evaluate the likelihood
      of finding dysplasia or incidental ileal pouch disorders in asymptomatic patients
      undergoing surveillance pouchoscopy. METHODS: This study included all eligible
      consecutive asymptomatic UC patients undergoing surveillance pouchoscopy to our
      subspecialty Pouchitis Clinic from 2002 to 2011. Univariable and multivariable
      analyses were performed. RESULTS: A total of 138 patients met the inclusion
      criteria, with 72 (52.2 %) being male. The mean age at pouch construction was
      45.4 +/- 15.0 years, and the mean interval from ileostomy closure to the
      inception of first surveillance pouchoscopy was 89.4 +/- 78.8 months. One patient
      was found to have indefinite for dysplasia on pouch body mucosal biopsy (0.7 %),
      and two patients had non-caseating granulomas, suggesting Crohn's disease (CD) of
      the pouch. Of the 138 patients, 69 (50 %) had abnormal endoscopic findings, 102
      (73.9 %) had acute and/or chronic inflammation on histology, and 62 (44.9 %) had
      both abnormal endoscopy and histology. The abnormal endoscopic findings included
      isolated pouch ulcer (n = 29, 21 %), active pouchitis (n = 31, 22.5 %),
      inflammatory polyps (n = 10, 7.2 %), strictures at the anastomosis (n = 5, 3.6
      %), inlet (n = 10, 7.2 %) or outlet (n = 2, 1.4 %). Thirteen patients (13/17,
      76.5 %) with pouch strictures underwent endoscopic balloon dilatation therapy and
      nine had (9/10, 90 %) endoscopic polypectomy. Multivariable analysis showed that
      patients with a preoperative diagnosis of CD and concomitant extraintestinal
      manifestations had a higher risk for abnormal pouch endoscopic findings with odds
      ratios of 2.552 (95 % confidence interval [CI] 1.108-16.545, p = 0.035) and 4.281
      (95 % CI 1.204-5.409, p = 0.014), respectively. CONCLUSIONS: Dysplasia was rare
      in asymptomatic patients with restorative proctocolectomy who underwent
      surveillance pouchoscopy in this cross-sectional study. However, "incidental"
      abnormal endoscopic and/or histologic findings were common, which often needed
      endoscopic therapeutic intervention.

PMID- 23877759
TI  - Laparoscopic repair of hiatal hernias: new classification supported by long-term
      results.
AB  - BACKGROUND: Mesh repair may decrease the recurrence rate but bears risk of
      esophageal complications. This study aimed to analyze the long-term results of
      laparoscopic hiatal repair depending on hiatal surface area (HSA). METHODS: The
      results from 658 procedures were analyzed. Group 1 had 343 patients with HSA
      smaller than 10 cm(2) (small hernias), for whom primary crural repair was
      performed. Group 2 had 261 patients with HSA size 10-20 cm(2) (large hernias),
      for whom primary crural repair (subgroup A) or mesh repair (subgroup B) was
      performed. Group 3 had 54 patients with HSA larger than 20 cm(2) (giant hernias),
      for whom only mesh repair was performed. RESULTS: The mean follow-up period was
      28.6 months (range, 10-48 months). Primary repair results in a higher recurrence
      rate for large hernias (11.9 %) than for small hernias (3.5 %) (p = 0.0016). For
      large hernias, the original method of sub-lay lightweight partially absorbable
      mesh repair provides a lower recurrence rate than primary repair (4.9 % vs 11.9
      %; p = 0.0488) and a comparable dysphagia rate (2.1 % vs 2.2 %; p = 0.6533). For
      giant hernias, mesh repair results in a higher recurrence rate than for large
      hernias (20 % vs 4.9 %; p = 0.0028). The analysis of variance (ANOVA) HSA
      recurrence ratio confirmed the correctness of the chosen threshold levels (10 and
      20 cm(2)) for subdividing hernias into three classes according to the new
      classification. CONCLUSIONS: The authors advise routine measurement of HSA and
      use of relative classification, primary suturing as the optimal repair for small
      hernias, the original technique of sub-lay lightweight partially absorbable mesh
      repair as the apparent best treatment for large hernias, and the original
      technique for giant hernias, which provides results corresponding to those
      reported in the literature, although these results require improvement.

PMID- 23877760
TI  - The impact of old age on surgical outcomes of totally laparoscopic gastrectomy
      for gastric cancer.
AB  - BACKGROUND: Old age is regarded as the risk factor of major abdominal surgery due
      to the lack of functional reserve and the increased presence of comorbidities.
      This study aimed to evaluate the impact of old age on the surgical outcomes of
      totally laparoscopic gastrectomy for gastric cancer. METHODS: This study enrolled
      389 gastric cancer patients who underwent totally laparoscopic gastrectomy at
      Hanyang University Guri Hospital and ASAN Medical Center. The patients were
      classified into two groups according to age as those older than 70 years and
      those younger than 70 years. Early surgical outcomes such as operation time,
      postoperative complications, time to first flatus, days until soft diet began,
      and hospital stay were evaluated. RESULTS: No patient was converted to open
      surgery. The two groups differed significantly in terms of overall postoperative
      complication rate, time to first flatus, days until soft diet began, and hospital
      stay. The patients who underwent Roux-en-Y gastrojejunostomy differed in
      incidence of postoperative ileus but not in severe postoperative complication
      rate. CONCLUSIONS: The results of this study demonstrated that old age can have
      an effect on the surgical outcomes of totally laparoscopic gastrectomy. This
      study especially showed that elderly patients are affected by the return of bowel
      movement after totally laparoscopic gastrectomy. On the other hand, however, it
      is presumed that old age has not had a serious impact on surgical outcomes in
      totally laparoscopic gastrectomy because no difference in the severe
      postoperative complication rate was observed.

PMID- 23877761
TI  - Routine histopathology for carcinoma in cholecystectomy specimens not evidence
      based: a systematic review.
AB  - BACKGROUND: Routine histopathological examination of gallbladder specimens is
      mainly performed to identify unexpected gallbladder carcinoma (GBC). This
      systematic review assesses the prevalence and characteristics of GBC in
      cholecystectomy specimens. METHODS: PubMed, EMBASE, Web of Science, and the
      Cochrane Library were searched for all articles reporting on the finding of GBC
      in cholecystectomy specimens. RESULTS: Of the 30 articles included, 20 were from
      Europe and the United States, and 10 were of Asian origin. In the Western
      studies, 276 cases of GBC were found in 61,542 specimens (median prevalence 0.4%,
      95% confidence interval [CI] 0.3-0.6). Of these, 65% were expected pre- or
      intraoperatively. In the Asian studies, 344 cases of GBC were found in 37,365
      specimens (median prevalence 1.2%, 95% CI 0.8-1.7). Of these, 45% were expected
      pre- or intraoperatively. In a subgroup analysis, identification of previously
      unexpected GBC affected treatment in only a minority of patients. In total, 72%
      of the patients received no further treatment and 32 patients (22%) received
      secondary surgery, of whom 15 patients survived at least 1 year. CONCLUSIONS: The
      histopathological finding of GBC after cholecystectomy appears to be a rare
      event. The prevalence of unexpected GBC was higher in Asian studies than in
      Western studies. The pre- and intraoperative sensitivity for this carcinoma is
      low. Moreover, the diagnosis of GBC at the time of histopathology is usually
      inconsequential. The results of this systematic review do not support routine
      histopathology of cholecystectomy specimens in clinical practice.

PMID- 23877762
TI  - Optimizing cost and short-term outcomes for elderly patients in laparoscopic
      colonic surgery.
AB  - BACKGROUND: Elderly patients often are regarded as high-risk for major abdominal
      surgery because of a lack of functional reserve and associated medical
      comorbidities. The goal of this study was to compare the cost of care and short
      term outcomes of elderly and nonelderly patients undergoing laparoscopic
      colectomy. Our hypothesis was that elderly patients managed with laparoscopic
      colorectal surgery and an enhanced recovery protocol (ERP) can realize the same
      benefits of lower hospital length of stay (LOS) without increasing hospital costs
      or readmission rates. METHODS: Review of a prospective database identified all
      patients that underwent an elective laparoscopic colectomy from 2009 to 2012.
      Patients were stratified into elderly (>=70 years old) and nonelderly (<70 years
      old) cohorts. The main outcome measures were discharge disposition, hospital
      costs, hospital LOS, and 30-day readmission rates between the laparoscopic and
      open groups. RESULTS: A total of 302 nonelderly (66%) and 153 elderly (34%)
      patients were included in the analysis. The elderly cohort had significantly
      higher comorbidities than the nonelderly group. There were no mortalities.
      Operative variables (procedure time, blood loss, and intraoperative
      complications) were similar. At discharge, significantly more elderly patients
      required temporary nursing or home care. There were no significant differences in
      short-term outcomes of LOS, 30-day readmission rates, or costs for the episode of
      care between the two groups. CONCLUSIONS: Combining laparoscopic colectomy with
      an ERP is cost-effective and results in similar short-term outcomes for the
      elderly and nonelderly patients. Despite higher comorbidities, elderly patients
      realized the same benefits of shorter LOS with similar hospital costs and
      readmission rates.

PMID- 23877763
TI  - Effectiveness and safety of minilaparoscopy-guided spleen biopsy: a retrospective
      series of 57 cases.

PMID- 23877764
TI  - Totally extraperitoneal inguinal hernia repair in patients previously having
      prostatectomy is feasible, safe, and effective.
AB  - BACKGROUND: The laparoscopic approach to repair of inguinal hernia has proven
      advantages over open repair. Repair of more technically challenging hernias, such
      as patients previously receiving prostatectomy, has been less studied and may not
      have these advantages. We aimed to compare safety, feasibility, and clinical
      outcomes for repairs in patients who previously underwent prostatectomy to
      control subjects. METHODS: We undertook a case-control study using a
      prospectively collected database. From 2004, all patients were routinely offered
      totally extraperitoneal laparoscopic repair. All patients who had a history of
      previous prostatectomy were identified and compared to a matched control group.
      Both operative and follow-up data were analyzed. RESULTS: Of 987 patients
      undergoing surgery during this time period, 52 prostatectomy patients were
      identified (44% open, 44% robotic, 3% laparoscopic) and matched to 102 control
      subjects. Accounting for bilateral repairs, 203 hernia repairs had been
      performed. Patients were well matched for age and American Society of
      Anesthesiologists score. Operative time was longer for prostatectomy patients
      (mean, 70 vs. 52 min, p < 0.0001); however, this reduced over time when comparing
      the first and second half prostatectomy patients (77 vs. 63 min, p = 0.144).
      Overall, there were no intraoperative or major postoperative complications and
      only one conversion (prostatectomy group). No significant differences were found
      for rates of minor postoperative complications, length of stay, or recurrence (n
      = 1, control group). No difference was observed for chronic pain, and all
      patients in each group reported satisfaction with surgery at contemporary follow
      up. CONCLUSIONS: In experienced hands, totally extraperitoneal inguinal hernia
      repair for patients previously having undergone prostatectomy is safe and has
      equivalent outcomes to patients not having undergone prostatectomy, and is an
      option to open repair. Understandably, slightly longer operative times may be
      justified, given the benefits of early discharge and less postoperative pain
      after laparoscopic surgery.

PMID- 23877765
TI  - Critical appraisal of learning curve for single incision laparoscopic right
      colectomy.
AB  - BACKGROUND: Single-incision laparoscopic colectomy (SILC) has emerged as a viable
      minimally invasive surgical approach with benefits and limitations yet to be
      fully elucidated. Although shown to be safe and feasible, characterization of the
      learning curve has not been addressed. Our aim was to identify a learning curve
      for SILC right hemicolectomy and to determine the incidence of operative failure
      and complication rates during this phase. METHODS: Over a 2-year period, data
      from 54 consecutive SILC cases performed by the same surgeon were tabulated in an
      institutional review board-approved database. A learning curve was generated
      utilizing cumulative sum (CUSUM) methodology to assess changes in total operative
      time (OT) across the case sequence. A separate learning curve was generated
      utilizing risk-adjusted CUSUM analysis, taking into account patient risk factors
      (i.e., age, American Society of Anesthesiologists score, body mass index, prior
      abdominal surgeries, and tumor size for malignant cases) and operative failure
      (i.e., prolonged OT, conversion to open surgery, intraoperative and 30-day
      postoperative complications, prolonged length of stay, reoperation, readmission,
      and mortality). RESULTS: Patients had a mean age of 63.6 +/- 11.5 years, mean
      body mass index of 27.3 +/- 3.9 kg/m(2), and median American Society of
      Anesthesiologists score of 2. Mean OT and length of stay were 123.5 +/- 28.9 min
      and 3.9 +/- 2.4 days, respectively. There were no conversions or oncologic
      failures. Six patients developed 30-day postoperative complications. CUSUM
      analysis of OT identified achievement of the learning phase after 30 cases. When
      taking into account both analyses, the rate of operative failure was not
      statistically different between the initial 30 and the final 24 cases.
      CONCLUSIONS: In our experience, the learning curve is achieved between 30 to 36
      cases. Offering this minimally invasive surgical approach does not result in
      increased complications or harmful results even in the early phases of the
      learning curve.

PMID- 23877766
TI  - Combined vascular and biliary fluorescence imaging in laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Bile duct injury in patients undergoing laparoscopic cholecystectomy
      is a rare but serious complication. Concomitant vascular injury worsens the
      outcome of bile duct injury repair. Near-infrared fluorescence imaging using
      indocyanine green (ICG) is a promising, innovative, and noninvasive method for
      the intraoperative identification of biliary and vascular anatomy during
      cholecystectomy. This study assessed the practical application of combined
      vascular and biliary fluorescence imaging in laparoscopic gallbladder surgery for
      early biliary tract delineation and arterial anatomy confirmation. METHODS:
      Patients undergoing elective laparoscopic cholecystectomy were enrolled in this
      prospective, single-institutional study. To delineate the major bile ducts and
      arteries, a dedicated laparoscope, offering both conventional and fluorescence
      imaging, was used. ICG (2.5 mg) was administered intravenously immediately after
      induction of anesthesia and in half of the patients repeated at establishment of
      critical view of safety for concomitant arterial imaging. During dissection of
      the base of the gallbladder and the cystic duct, the extrahepatic bile ducts were
      visualized. Intraoperative recognition of the biliary structures was registered
      at set time points, as well as visualization of the cystic artery after repeat
      ICG administration. RESULTS: Thirty patients were included. ICG was visible in
      the liver and bile ducts within 20 minutes after injection and remained up to
      approximately 2 h, using the ICG-filter of the laparoscope. In most cases, the
      common bile duct (83%) and cystic duct (97%) could be identified significantly
      earlier than with conventional camera mode. In 13 of 15 patients (87%),
      confirmation of the cystic artery was obtained successfully after repeat ICG
      injection. No per- or postoperative complications occurred as a consequence of
      ICG use. CONCLUSION: Biliary and vascular fluorescence imaging in laparoscopic
      cholecystectomy is easily applicable in clinical practice, can be helpful for
      earlier visualization of the biliary tree, and is useful for the confirmation of
      the arterial anatomy.

PMID- 23877767
TI  - The role of aerosolized intraperitoneal heparin and hyaluronic acid in the
      prevention of postoperative abdominal adhesions.
AB  - INTRODUCTION: Intraperitoneal adhesions are a common and serious problem
      following abdominal surgery. Significant research has been performed to
      investigate the mechanisms involved; however, this has not influenced the
      incidence; it is still the leading cause of intestinal obstruction, pelvic pain,
      and infertility in women. The purpose of this study was to evaluate the ability
      of aerosolized heparin and hyaluronic acid for the prevention of postoperative
      adhesions. MATERIALS AND METHODS: A survival pig model was employed (N = 40). The
      pigs underwent laparoscopic insertion of polypropylene mesh to create
      intraperitoneal adhesions. The animals were randomized into four groups: control
      (n = 10), aerosolized heparin (n = 10), aerosolized hyaluronic acid (n = 10), and
      aerosolized mixture of both agents (n = 10). After a 2-week recovery period, the
      animals were killed and intraperitoneal adhesions were assessed. RESULTS: All of
      the animals in the control group suffered postoperative adhesions (10/10)
      compared with three in the heparin group, two in the hyaluronic group, and one in
      the mixed group. The number of adhesions per animal and the severity was higher
      in the control group compared with the therapeutic groups. The mean number of
      adhesions in the affected pigs also was higher in the control group compared with
      the therapeutic groups: 3.3 versus 0.4 in heparin group (range 0-2) versus 0.3 in
      hyaluronic acid group versus 0.1 in the mixed group (p = 0.002). CONCLUSIONS:
      This study has shown that aerosolised heparin and hyaluronic acid is an effective
      method to prevent postoperative adhesions whether they were used independently or
      in synergism. However, the best result was when both agents mixed together
      compared with the control. A human-based study will be the next step to confirm
      the success of these agents.

PMID- 23877768
TI  - Impact of obesity on maternal and neonatal outcomes in insulin-resistant
      pregnancy.
AB  - OBJECTIVE: To determine the impact of obesity on pregnancies complicated by
      insulin resistance. STUDY DESIGN: Secondary analysis of prospective cohort of
      women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM).
      The exclusion criteria were type 1 DM, multiple gestation, fetal anomalies,
      unknown prepregnancy, and body mass index (BMI). Primary maternal outcome was a
      composite of any of the following: severe preeclampsia, eclampsia, third- to
      fourth-degree laceration, readmission, wound infection, or antepartum
      hospitalization. Primary neonatal outcome was a composite of any of the
      following: hypoglycemia, preterm delivery, admission to level 3 nursery, oxygen
      requirement > 6 hours after birth, shoulder dystocia, 5-minute Apgar <=3, cord pH
      < 7.0, and cord base excess < -12 mmol/L. Obese women (BMI >=30.0 kg/m(2)) were
      compared with nonobese women (BMI < 30.0 kg/m(2)). RESULTS: Of 356 subjects with
      DM, 233 (66%) were obese. Obese women were not at further increased risk of the
      composite maternal outcome (adjusted odds ratio [AOR] = 0.68, 95% confidence
      interval [CI] = 0.43-1.09), the composite neonatal outcome (AOR = 0.76, 95% CI =
      0.48-1.21), or cesarean (58.8 vs. 52.9%, p = 0.28, AOR = 1.47, 95% CI = 0.91
      2.39). CONCLUSION: We did not find evidence that obesity worsened pregnancy
      outcomes in women with GDM and type 2 DM, suggesting that obese women may not
      require more stringent antepartum treatment strategies.

PMID- 23877769
TI  - Assessing decoding ability: the role of speed and accuracy and a new composite
      indicator to measure decoding skill in elementary grades.
AB  - Tools for assessing decoding skill in students attending elementary grades are of
      fundamental importance for guaranteeing an early identification of reading
      disabled students and reducing both the primary negative effects (on learning)
      and the secondary negative effects (on the development of the personality) of
      this disability. This article presents results obtained by administering existing
      standardized tests of reading and a new screening procedure to about 1,500
      students in the elementary grades in Italy. It is found that variables measuring
      speed and accuracy in all administered reading tests are not Gaussian, and
      therefore the threshold values used for classifying a student as a normal decoder
      or as an impaired decoder must be estimated on the basis of the empirical
      distribution of these variables rather than by using the percentiles of the
      normal distribution. It is also found that the decoding speed and the decoding
      accuracy can be measured in either a 1-minute procedure or in much longer
      standardized tests. The screening procedure and the tests administered are found
      to be equivalent insofar as they carry the same information. Finally, it is found
      that speed and accuracy act as complementary effects in the measurement of
      decoding ability. On the basis of this last finding, the study introduces a new
      composite indicator aimed at determining the student's performance, which
      combines speed and accuracy in the measurement of decoding ability. 

PMID- 23877770
TI  - Educational differences in smoking among adolescents in Germany: what is the role
      of parental and adolescent education levels and intergenerational educational
      mobility?
AB  - BACKGROUND: Adolescence is the period in which smoking onset usually occurs and
      the course for future socioeconomic status (SES) is set. However, because of the
      transitional nature of adolescence, it is questionable whether health
      inequalities are best measured by indicators of parental SES or rather by
      indicators of the adolescents' own developing SES. We examine the independent
      effects of parental and adolescent education and intergenerational educational
      mobility on adolescent smoking behaviour while controlling for differences in
      parental and close friends' smoking behaviour. METHODS: The study is based on
      data from a subsample (12-17 years, n = 5,053) of the nationally representative
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS). Participants reported their education level as well as their personal
      and close friends' smoking behaviour. Information on parental education and
      smoking behaviour was obtained via parent interviews. Adolescent and parental
      education data were dichotomized (low/high), leading to four categories of
      intergenerational educational mobility: stable high, potentially upwardly mobile,
      potentially downwardly mobile, and stable low. RESULTS: After adjustment for
      parental and close friends' smoking behaviour, adolescent smoking habits were
      strongly related to their personal education level, but not that of their
      parents. Among boys, both stable low and downwardly mobile adolescents had a 2.7
      fold increased risk of being a smoker compared with peers with a stable high
      education. Among girls, only those with a stable low education had a 2.2-fold
      increased risk of smoking. Among both genders, educational upward mobility was
      associated with significantly lower smoking rates compared with peers with a
      stable low education (boys: OR 0.32; 95% CI 0.20-0.53; girls: OR 0.52; 95% CI
      0.37-0.73). CONCLUSIONS: Our results show that the risk of an adolescent smoking
      is influenced by their own education level rather than that of their parents.
      Educational upward mobility seems to be protective against becoming a smoker in
      youth. Boys who experience downward mobility tend to have a significantly higher
      inclination to smoke than their peers with a stable high education. These
      findings illustrate the potential public health benefits of investments in
      education and help identify high-risk groups for smoking onset.

PMID- 23877771
TI  - Assessment of interfacial defects at composite restorations by swept source
      optical coherence tomography.
AB  - ABSTRACT. In clinical dental practice, it is often difficult or even impossible
      to detect and assess interfacial adhesive defects at adhesive restorations by
      means of visual inspection or other established diagnostic methods. However,
      nondestructive optical coherence tomography (OCT) may provide a better picture in
      this diagnostic scenario. The aim of this study was to evaluate the suitability
      of swept source OCT (SS-OCT) for the nondestructive assessment of interfacial
      deficiencies at composite restorations and the evaluation of cohesive defects
      within composite material. Ten class V composite restorations that were not
      adhesively luted were taken as validation objects and examined for frequency of
      interfacial gaps, air entrapments, and defects between composite layers using SS
      OCT with a 1325-nm center wavelength. Light microscopy was used to inspect for
      inherent structures. SS-OCT detected 79.5%+/-1.8% of the total gap lengths at the
      enamel interface and 70.9%+/-0.4% at the dentin interface. Additionally,
      defective structures in composite restorations were displayed. It was shown that
      OCT imaging has the potential to nondestructively assess the interfacial
      adaptation of composite restorations and to detect internal defects in the
      layered composite material. 

PMID- 23877773
TI  - The Tactical Combat Casualty Care Casualty Card TCCC Guidelines ? Proposed Change
      1301.
AB  - Optimizing trauma care delivery is paramount to saving lives on the battlefield.
      During the past decade of conflict, trauma care performance improvement at combat
      support hospitals and forward surgical teams in Afghanistan and Iraq has
      increased through Joint Trauma System and DoD Trauma Registry data collection,
      analysis, and rapid evidence-based adjustments to clinical practice guidelines.
      Although casualties have benefitted greatly from a trauma system and registry
      that improves hospital care, still lacking is a comprehensive and integrated
      system for data collection and analysis to improve performance at the prehospital
      level of care. Tactical Combat Casualty Care (TCCC) based casualty cards, TCCC
      after action reports, and unit-based prehospital trauma registries need to be
      implemented globally and linked to the DoD Trauma Registry in a seamless manner
      that will optimize prehospital trauma care delivery. 

PMID- 23877772
TI  - In vivo photoacoustic lifetime imaging of tumor hypoxia in small animals.
AB  - Tumor hypoxia is an important factor in assessment of both cancer progression and
      cancer treatment efficacy. This has driven a substantial effort toward
      development of imaging modalities that can directly measure oxygen distribution
      and therefore hypoxia in tissue. Although several approaches to measure hypoxia
      exist, direct measurement of tissue oxygen through an imaging approach is still
      an unmet need. To address this, we present a new approach based on in vivo
      application of photoacoustic lifetime imaging (PALI) to map the distribution of
      oxygen partial pressure (pO2) in tissue. This method utilizes methylene blue, a
      dye widely used in clinical applications, as an oxygen-sensitive imaging agent.
      PALI measurement of oxygen relies upon pO2-dependent excitation lifetime of the
      dye. A multimodal imaging system was designed and built to achieve ultrasound
      (US), photoacoustic, and PALI imaging within the same system. Nude mice bearing
      LNCaP xenograft hindlimb tumors were used as the target tissue. Hypoxic regions
      were identified within the tumor in a combined US/PALI image. Finally, the
      statistical distributions of pO2 in tumor, normal, and control tissues were
      compared with measurements by a needle-mounted oxygen probe. A statistically
      significant drop in mean pO2 was consistently detected by both methods in tumors.

PMID- 23877774
TI  - [Presence of Bordetella holmesii in an outbreak of pertussis in Chile].
AB  - The incidence of whooping cough in Chile ranges from 4.1 and 7.5 per hundred
      thousand inhabitants. B. pertussis detection is performed by Real Time PCR (Q
      PCR) directed to the insertion sequence IS481. However, this sequence is also
      found in the genome of B. bronchiseptica and B. holmesii. The latter is also a
      respiratory pathogen whose clinical features are similar to B. pertussis.
      However, it is important to differentiate between these species because in
      immunosuppressed patients B. holmesii is more likely to cause bacteremia and is
      less susceptible to erythromycin. The goal of this work is to measure
      prospectively and retrospectively the presence of B. holmesii in samples reported
      positive for B. pertussis in the period 2010-2011. During this period, 1994
      nasopharyngeal specimens entered the laboratory for Bordetella sp. PCR, of which
      224 were positive. The analysis by Q-PCR directed to the recA gene of B. holmesii
      of all 224 positive samples determined a prevalence of B. holmesii of 0.6%
      (12/1994). Because of its more aggressive behavior in immunosupressed patients
      and its different resistance pattern, routine screening of B. pertussis and B.
      holmesii is currently performed for all samples in which Bordetella sp PCR is
      initially detected. 

PMID- 23877775
TI  - [Species distribution and susceptibility pattern of Candida spp.: the importance
      to survey also strains isolated from the community].
AB  - BACKGROUND: The most of the surveillance studies has been conducted in
      hospitalized patients with invasive infections. Recently, new clinical
      breakpoints (CBPs) have been proposed for antifungal susceptibility testing and
      epidemiological cutoffs (ECVs). AIM: To evaluate species distribution and
      susceptibility pattern of Candida spp. obtained from in and outpatients in a
      period of 6 months. MATERIAL AND METHODS: The isolates (n=223) came from vaginal
      discharge (51.6%), lower respiratory tract (24.7%), urine (20.2%), wounds (1.8%),
      blood (0.9%), peritoneal fluid (0.4%) and nails (0.4%). RESULTS: The species
      distribution was C. albicans 84.8% (n: 189), C. glabrata 7.6% (n: 17), C.
      tropicalis 2.7% (n: 6), C. parapsilosis 2.2% (n: 5), C. kefyr 0.9% (n: 2) and
      others 1.8% (C. krusei, C. lusitanie, C. guilliermondii, C. intermedia) (n: 4).
      The susceptibility dose dependence (SDD) and resistance were 3.2% for fluconazole
      and 2.2% for voriconazole. The most of SDD and resistant strains were isolated
      from ambulatory patients. Also, a higher percentage of MICs over the new CBPs and
      ECVs were found in strains from ambulatory patients and especially in C. glabrata
      isolates to caspofungin. CONCLUSION: Taking into consideration that most of the
      invasive infections are caused by strains from the endogenous microbiota, and
      that there is a resistant population of Candida spp. in the community, should be
      important to include in surveillance studies strains isolated from ambulatory
      patients.

PMID- 23877776
TI  - [Prevalence of leptospirosis in vague dogs captured in Temuco City, 2011].
AB  - BACKGROUND: Leptospirosis, a bacterial disease of worldwide distribution, affects
      various animals and is considered a zoonosis. It can be transmitted directly or
      indirectly, mainly through contact with the carrier's urine and entering the body
      through mucous membranes or skin. In the city of Temuco, there are no
      epidemiological studies of canine leptospirosis and the country data are scarce.
      OBJECTIVE: To determine the prevalence of leptospirosis in stray dogs of the city
      of Temuco. MATERIAL AND METHODS: In a cross- sectional study, 400 dogs admitted
      to Temuco Kennel during the year 2011 were sampled. Blood samples were analyzed
      using a modified commercial ELISA kit. RESULTS: The prevalence of leptospirosis
      was 21.3%. Positive cases were concentrated in dogs 5 to 8 years of age,
      independent of gender. DISCUSSION: The high prevalence found demonstrates the
      need for further studies to better understand the epidemiology of the disease and
      to establish prevention and control measures.

PMID- 23877777
TI  - [Combined norms for the prevention of vertical transmission of HIV and syphillis
      infection].

PMID- 23877778
TI  - [Syphilis and gonorrhea surveillance].

PMID- 23877779
TI  - [Histoplasma capsulatum var. capsulatum Darling].

PMID- 23877780
TI  - [Exanthematic typhus epidemic in Chile (1932-1939)].
AB  - After the great epidemic of the exanthematic typhus of 1918-1919 in Chile, there
      was a gradual decrease in the number of cases , until it became endemic around
      1926. Starting in 1932 and until 1939 a new epidemic outbreak occured that
      prompted researchers to its study supported by the new clinical and technological
      advances of this period. Subsequently, two important events occured: the
      erradication of the vector ( human louse) by means of effective insecticides and
      the discovery of an effective antibiotic treatment.

PMID- 23877781
TI  - [Allergic rhinosinusitis by Curvularia inaequalis (Shear) Boedijn].
AB  - Curvularia inaequalis (Shear) Boedijn is a fungus dematiaceo, saprophyte and
      plant pathogen found mainly in tropical and subtropical areas, associated with
      various organic substrates. Rarely been identified in systemic infections, skin
      and there is only one report of allergic rhinosinusitis described above. A case
      of allergic fungal rhinosinusitis by Curvularia inaequalis (Shear) Boedijn in
      which diagnosis was considered the signs and symptoms, sinus CT and cultivation
      of mucin.The patient was treated with endoscopic surgical toilet, plus use of
      inhaled steroids and itraconazole systemic. With good clinical response, is
      asymptomatic at one year. 

PMID- 23877782
TI  - [Report of case of subcutaneous cysticercosis].
AB  - Infection of the larval form (cysticerco) of Taenia in any tissue or organ is
      known as the disease cysticercosis. Many sites of infection have been documented
      but the central nervous system has been the most common. It present a case report
      of a 19 years old patient with a subcutaneous cysticercosis confirmed with
      biopsy. 

PMID- 23877783
TI  - [Treatment failure due to acquisition of antibiotic resistance: report of two
      clinical cases].
AB  - OBJECTIVE: We describe two cases of treatment failure due to intra-treatment
      acquisition of antibiotic resistant microorganisms with the aim of highlighting
      the possible molecular mechanisms by which treatment failure occurred. PATIENTS
      AND METHODS: We analyzed the clinical histories and the isolates obtained from 2
      patients, one with a urinary tract infection (UTI) by E. coli, initially treated
      with cefuroxim (to which the isolate was susceptible), and another with
      osteoarthritis (OA) treated initially with meropenem plus vancomycin, developing
      K. pneumoniae susceptible to meropenem. During treatment, in both patients,
      resistant microorganisms were isolated, and empirical therapy was modified,
      initially with ceftriaxone and afterwards meropenem in case 1, and adding
      amikacin in case 2. Both strains (per patient) were compared by PFGE and
      resistance genes were sought by PCR. RESULTS: Regarding the UTI, the initial
      strain acquired an IncFIB SHV-5-producing plasmid. In the OA case, the initial
      susceptible strain was substituted by a CTX-M-9 and AadB-AadA2-Aac(6')Ib
      producing K. pneumoniae.

PMID- 23877784
TI  - [Bacteremia and pneumonia due to Alcaligenes xylosoxidans in a immunocompetent
      patient].

PMID- 23877785
TI  - [Cost-effectiveness of screening for latent tuberculosis in healthcare workers].

PMID- 23877786
TI  - Does prepubertal testicular tissue vitrification influence spermatogonial stem
      cells (SSCs) viability?
AB  - PURPOSE: Testicular cryopreservation prior to chemotherapy or radiotherapy in
      children with cancer is one of the ways to preserve fertility. However,
      cryopreservation may cause damage to the testicular parenchyma cells. The
      objective of this study was to investigate effects of vitrification on the
      intracellular LDH leakage, cell cycle/apoptotic responses and apoptosis-related
      gene expression patterns in the spermatogonial stem cells (SSCs) obtained from
      the vitrified testis. METHODS: The testes of the mice pups (6-day-old, BALB/c)
      both vitrified and fresh groups were digested with enzymes (collagenase,
      DNaseIota, trypsin-EDTA) to disperse the cells. The SSCs, type A, were isolated
      from the rest of testicular cells by MACS. The amount of damage to the SSCs
      immediately was evaluated by Cytotoxicity assay, Flow cytometry assay and Real
      time PCR. RESULTS: The intracellular LDH leakage in the SSCs,harvested from the
      vitrified testes, was less reported compared with the fresh ones. Moreover, the
      percentage of apoptotic and necrotic SSCs obtained from the vitrified testes was
      lower than that of yielded from the fresh samples. Also, the apoptosis-related
      genes of the SSCs,collected from the vitrified testes, changed their expression
      profile as increasing P53 and BCL-2 expression levels and decreasing Bax and Fas
      expression levels. CONCLUSIONS: The study indicates that vitrification of
      prepubertal testicular tissue does not increase the expression profile of
      apoptosis-related genes such as Bax and Fas in the testicular SSCs consistent
      with diminished cell apoptotic/necrotic responses and no increasing intracellular
      LDH leakage.

PMID- 23877787
TI  - MicroRNA-29a regulates the benzo[a]pyrene dihydrodiol epoxide-induced DNA damage
      response through Cdc7 kinase in lung cancer cells.
AB  - Cdc7 kinase is a key regulator of DNA replication and has an important role in
      the cellular DNA damage response by controlling checkpoint signaling and cell
      survival. Yet, how the activity of Cdc7 kinase is regulated is poorly understood.
      In silico analysis identified microRNA-29 (miR-29)-binding sites in the 3'
      untranslated region (UTR) of both Cdc7 and its activating subunit Dbf4. We show
      that miR-29a binds to Cdc7 and Dbf4 3'-UTRs and regulates kinase levels. We find
      that in response to DNA damage, upregulation of Cdc7 kinase correlates with a
      downregulation in miR-29a. Enforced miR-29a expression prevents the accumulation
      of Cdc7 in response to the environmental genotoxin, benzo[a]pyrene dihydrodiol
      epoxide (BPDE) present in cigarette smoke, resulting in aberrant checkpoint
      signaling and increased cell lethality. As BPDE sensitivity was rescued by
      overexpression of miRNA-resistant Cdc7/Dbf4, we propose that Cdc7 kinase is an
      important target of miR-29a in determining cell survival from genotoxic stress
      caused by this environmental toxin. 

PMID- 23877789
TI  - Synthesis and in vitro evaluation of a multifunctional and surface-switchable
      nanoemulsion platform.
AB  - We present a multifunctional nanoparticle platform that has targeting moieties
      shielded by a matrix metalloproteinase-2 (MMP2) cleavable PEG coating. Upon
      incubation with MMP2 this surface-switchable coating is removed and the targeting
      ligands become available for binding. The concept was evaluated in vitro using
      biotin and alphavbeta3-integrin-specific RGD-peptide functionalized
      nanoparticles. 

PMID- 23877788
TI  - Block of P2X7 receptors could partly reverse the delayed neuronal death in area
      CA1 of the hippocampus after transient global cerebral ischemia.
AB  - Transient global ischemia (which closely resembles clinical situations such as
      cardiac arrest, near drowning or severe systemic hypotension during surgical
      procedures), often induces delayed neuronal death in the brain, especially in the
      hippocampal CA1 region. The mechanism of ischemia/reperfusion (I/R) injury is not
      fully understood. In this study, we have shown that the P2X7 receptor antagonist,
      BBG, reduced delayed neuronal death in the hippocampal CA1 region after I/R
      injury; P2X7 receptor expression levels increased before delayed neuronal death
      after I/R injury; inhibition of the P2X7 receptor reduced I/R-induced microglial
      microvesicle-like components, IL-1beta expression, P38 phosphorylation, and glial
      activation in hippocampal CA1 region after I/R injury. These results indicate
      that antagonism of the P2X7 receptor and signaling pathways of microglial MV
      shedding, such as src-protein tyrosine kinase, P38 MAP kinase and A-SMase, might
      be a promising therapeutic strategy for clinical treatment of transient global
      cerebral I/R injury. 

PMID- 23877790
TI  - HIV prevalence and related risk behaviors in men who have sex with men, Yemen
      2011.
AB  - Men who have sex with men (MSM) are at growing risk of HIV infection in many
      parts of the world; however, the epidemic has not been well explored among this
      population in most Arab countries. To estimate the prevalence of HIV and related
      risk behaviors among MSM in Yemen, we recruited 261 adult MSM from the port
      cities of Aden and Al-Hudaydah through venue- and facility-based sampling.
      Behavioral data were collected with a face-to-face questionnaire, and HIV status
      was determined by serological testing. HIV prevalence was 5.9 % (95 % CI 4.8
      7.3). One-fourth (25.8 %, 95 % CI 20.7-31.5) had tested for HIV in the last year
      and received results; 27.8 % (95 % CI 22.5-33.7) had comprehensive knowledge
      about HIV; 20.0 % (95 % CI 15.8-25.0) reported condom use at last anal sex; and
      31.4 % (95 % CI 25.9-37.3) reported that they or their sexual partner had a
      sexually transmitted disease symptom. Injecting drugs in the last year was
      reported by 0.8 % (95 % CI 0.1-9.2). Multiple risk behaviors, low HIV knowledge,
      few preventive behaviors, and HIV prevalence greater than 5 % denote a
      concentrated and potentially expanding HIV epidemic among MSM in Yemen. No time
      should be lost in intervening to prevent further expansion of the epidemic to
      levels already seen among MSM outside the Middle East. 

PMID- 23877791
TI  - Adherence to post-exposure prophylaxis for non-forcible sexual exposure to HIV: a
      systematic review and meta-analysis.
AB  - To characterize adherence to post-exposure prophylaxis after non-forcible sexual
      exposure to HIV, we conducted a review of the literature and meta-analysis.
      Articles were considered if they contained primary adherence data following non
      forcible sexual exposure. Random-effects meta-analysis was used to create pooled
      point estimates for adherence. Of 1,257 abstracts identified through our search
      algorithm, 17 were eligible for inclusion in this review, representing 3,634
      patients enrolled in 3 randomized controlled trials (RCTs), 9 prospective and 5
      retrospective observational studies. Pooled adherence, primarily assessed by self
      report, was 77 % [95 % confidence interval (CI) 68-87] in prospective
      observational studies, 81 % (95 % CI 65-96) in retrospective studies, 78 % (95 %
      CI 65-91) in RCTs, and 78 % (95 % CI 72-85) overall. Overall adherence was
      moderately high, with high variability between studies. Assessment of adherence
      could be enhanced by the use of objective measurements. 

PMID- 23877792
TI  - Improvement of superovulatory response and pregnancy rate after transfer of
      embryos recovered from Japanese Black cows fed rumen bypass polyunsaturated fatty
      acids.
AB  - Feeding rumen bypass polyunsaturated fatty acids (PUFA) affects to Japanese Black
      cows affects their reproduction, though its influence on superovulatory response
      in donor cows and conception in recipient cattle has not been well studied. Here,
      we investigated the effects of feeding PUFA to Japanese Black cows on blood
      biochemistry, the numbers of ova and embryos or transferable embryos and
      pregnancy rate following embryo transfer (ET) to recipient Holstein heifers. PUFA
      (40% linoleic acid) was fed at 300 g/day in the experimental group from the last
      day of estrus until the day of artificial insemination for superovulatory
      treatment. Blood was collected on the first day of follicle-stimulating hormone
      administration. Total cholesterol level was significantly higher in the 15- to 19
      day feeding group (117.4 mg/dl) than in the control group (95.0 mg/dl). The
      numbers of ova and embryos or transferable embryos were significantly higher in
      the 15- to 19-day feeding group than in the control group. The numbers of
      transferable embryos in the 15- to 19-day feeding group were significantly higher
      than in the 10- to 14-day feeding group. The pregnancy rate at day 60 was
      significantly higher in the experimental group (66.7 and 57.1%) than in the
      control group (51.1 and 44.0%) after transfer of fresh and frozen-thawed embryos,
      respectively. In conclusion, the numbers of ova and embryos or transferable
      embryos after superovulatory treatment increased, and the pregnancy rate after ET
      was higher in Japanese Black cows fed PUFA than in the control group. 

PMID- 23877793
TI  - K-ras gene mutation as a predictor of cancer cell responsiveness to metformin.
AB  - An increasing number of studies support the use of metformin, a common
      antidiabetic drug, as a novel anticancer therapeutic. However, its mechanism of
      action has yet to be identified. In the current study, metformin was observed to
      effectively inhibit the growth of the K-ras mutant but not wild-type tumors in
      vivo. The antitumor effects of metformin were mediated by the induction of
      apoptosis and inhibition of proliferation in vivo. In addition, metformin induced
      apoptosis in the K-ras mutant tumors, A549 and PANC-1, but not in the K-ras wild
      type tumor, A431, in vitro. Similarly, at lower concentrations, metformin
      inhibited cell proliferation in the K-ras mutant, but not in the K-ras wild-type
      tumor cells in vitro. These observations indicate that tumors with K-ras
      mutations are sensitive to metformin therapy. In addition, metformin
      significantly arrested K-ras mutant and wild-type tumor cells in G1 phase in
      vitro and metformin downregulated two important downstream effectors of the Ras
      signaling pathway in K-ras mutant tumors. Metformin was concluded to function as
      a potential K-ras-targeting agent that has potential for cancer therapy.

PMID- 23877794
TI  - Role of cysteine 288 in nucleophosmin cytoplasmic mutations: sensitization to
      toxicity induced by arsenic trioxide and bortezomib.
AB  - Mutations in exon 12 of the nucleophosmin (NPM1) gene (NPMc+ (NPM1 COOH terminal
      mutations)) define a distinct subset of acute myelogenous leukemias (AMLs), in
      which the NPMc+ protein localizes aberrantly to the leukemic cell cytoplasm. We
      have found that introduction of the most common NPMc+ variant into K562 and 32D
      cells sensitizes these cells to apoptosis induced by drugs such as bortezomib and
      arsenic trioxide (ATO) that induce reactive oxygen species (ROS) formation, and
      that cytotoxicity is prevented in the presence of N-acetyl-L-cysteine (NAC), an
      ROS scavenger. The substitution of tryptophan 288 (W288) by cysteine occurs in
      the great majority of NPM1c+ mutations. Mutagenesis of cysteine 288 to alanine re
      localizes NPMc+ from the cytoplasm to the nucleolus and attenuates the
      sensitivity of cells expressing this mutation to bortezomib and ATO. Primary AML
      cells expressing NPMc+ are also significantly more sensitive than other AML cells
      to apoptosis induced by both drugs at pharmacologically achievable doses. We
      conclude that the presence of a cysteine moiety at position 288 results in the
      cytoplasmic localization of NPM1c+ and the increased sensitivity to bortezomib
      and ATO. These data suggest that bortezomib and ATO may have increased
      therapeutic efficacy in NPM1c+ leukemias. 

PMID- 23877795
TI  - Neurology and international organizations.
AB  - A growing number of international stakeholders are engaged with neurologic
      diseases. This article provides a brief overview of important international
      stakeholders in the practice of neurology, including global disease-specific
      programs, United Nations agencies, governmental agencies with international
      influence, nongovernmental organizations, international professional
      organizations, large private donors, private-public partnerships, commercial
      interests, armed forces, and universities and colleges. The continued engagement
      of neurologists is essential for the growing number of international
      organizations that can and should incorporate neurologic disease into their
      global agendas. 

PMID- 23877796
TI  - De novo arteriovenous malformation after brain radiotherapy for medulloblastoma
      in a child.

PMID- 23877797
TI  - Clinical reasoning: a 39-year-old woman with progressive proximal weakness.

PMID- 23877798
TI  - Re: Tumefactive multiple sclerosis lesions under fingolimod treatment.

PMID- 23877799
TI  - Re: Stroke in sub-Saharan Africa: an urgent call for prevention.

PMID- 23877800
TI  - Teaching NeuroImages: spontaneous thalamic hemorrhage causing convergence excess.

PMID- 23877801
TI  - Teaching NeuroImages: perfusion imaging of cerebral hyperperfusion syndrome
      following revascularization.
AB  - A 69-year-old man developed acute-onset confusion and hypertension with systolic
      pressures in the 160s 1 day after carotid endarterectomy for right facial droop
      from left hemispheric lacunar infarcts. CT perfusion (figure, A-D) demonstrated
      findings consistent with cerebral hyperperfusion syndrome (CHS) following
      revascularization. CHS is caused by loss of autoregulation, hypertension, and
      ischemia-reperfusion injury resulting in increased regional blood flow and
      vascular congestion.(1) CHS following revascularization may present as
      ipsilateral headache, focal seizure, or neurologic deficit. Nonperfusion imaging
      may show intraparenchymal hemorrhage or edema. Labetalol and clonidine are used
      for aggressive blood pressure control until cerebral autoregulation is
      restored.(2.) 

PMID- 23877803
TI  - Developing a universal framework for communication during intraoperative crises:
      lessons learned from aviation.

PMID- 23877802
TI  - Carvacrol attenuates diabetes-associated cognitive deficits in rats.
AB  - Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been
      demonstrated to possess various biological actions. The present study was
      designed to investigate the neuroprotective effect of CAR on diabetes-associated
      cognitive deficit (DACD) in a rat model of diabetes and exploring its potential
      molecular mechanism. Diabetic rats were treated with CAR by the doses of 25, 50,
      and 100 mg/kg for 7 weeks. Morris water maze was used for behavioral evaluation
      of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus
      were prepared for the quantification of oxidative stress (MDA, SOD, and GSH), NF
      kappaB p65 unit, TNF-alpha, IL-1beta, and caspase-3. After 7 weeks of
      streptozotocin injection, the rats produced remarkable increase in escape
      latency, coupled with increased oxidative stress (increased MDA level and
      decreased SOD as well as reduced GSH), NF-kappaB p65 unit, TNF-alpha, IL-1beta,
      and caspase-3 in different regions of diabetic rat brain. Interestingly,
      coadministration of CAR significantly and dose-dependently prevented behavioral,
      biochemical, and molecular changes associated with diabetes. In summary, our
      findings provide the first evidence that CAR can remarkably attenuate DACD and
      suggest the involvement of oxidative stress, inflammation, and apoptotic cascades
      in the development of cognitive impairment caused by diabetes. The
      pharmacological effect of CAR suggests that it may be used as a promising agent
      for the treatment of conventional antihyperglycemic regiments as well as DACD.

PMID- 23877804
TI  - Clinical significance of Delphian lymph node metastasis in papillary thyroid
      carcinoma.
AB  - BACKGROUND: Delphian lymph node (DLN) metastasis has long been considered a
      prognostic marker of head and neck malignancy. These days, the significance of
      DLN in thyroid cancer has come to the fore. The objective of the present study
      was to evaluate the clinical significance of DLN metastasis in patients with
      papillary thyroid cancer (PTC). PATIENTS AND METHODS: The study was carried out
      between July 2009 and December 2011, and DLN was detected in 245 of 898 PTC
      patients who underwent total thyroidectomy and bilateral central compartment neck
      dissection. In those 245 patients DLN status was correlated with clinical and
      pathologic factors, including age, gender, tumor size, extrathyroidal extension
      (ETE), lymphovascular invasion (LVI), and central and lateral nodal metastasis.
      RESULTS: DLN metastasis was found in 20 % of the patients studied (49 of 245),
      and DLN metastasis was correlated with tumor size, multicentricity, bilaterality,
      and LVI excluding ETE (all p < 0.05). The proportion of male patients was higher
      in the DLN metastasis positive group than in the DLN metastasis negative group
      (34.7 vs. 13.3 %; p < 0.05). Most of the patients (95.9 %) with DLN metastasis
      had other central neck node metastasis, and the metastatic central lymph node
      ratio was higher (0.38 +/- 0.23 versus 0.09 +/- 0.16; p < 0.001) and lateral neck
      node metastasis was more common (2.6 vs. 32.7 % <0.001) than in patients without
      DLN metastasis. For central and lateral compartment nodal metastasis, DLN status
      had sensitivity, specificity, positive and negative predictive values of 100,
      37.4, 58.1, and 100 %, and 85.3, 76.2, 97.4, and 32.7 %, respectively.
      Multivariate analysis showed that the factors affecting DLN involvement were
      tumor size and LVI. Patients with positive DLN were ~1.6 times more likely to
      have further central compartment disease and 3.6 times more likely to have
      lateral compartment disease. CONCLUSIONS: DLN metastasis in patients with PTC is
      related to a number of poor prognostic factors. Furthermore DLN involvement
      implies that the patients are predicted to have heavy burden of central neck node
      metastasis and are more likely to have further lateral neck node metastasis. It
      is recommended that DLN is evaluated and dissected in all patients with thyroid
      cancer. If DLN metastasis is suspected, the surgeon should thoroughly dissect the
      central neck compartment and pay particular attention to the lateral lymph node
      compartments.

PMID- 23877805
TI  - [Teachers and pillars of the institute].

PMID- 23877806
TI  - [Risk factors for the development of thrombotic complication in patients with
      lupus erythematosus and lupus nephropatic].
AB  - INTRODUCTION: Thrombotic events constitute a frequent complication in patients
      with systemic lupus erythematosus (SLE) and are associated with increased
      morbidity and mortality of these patients. OBJECTIVE: To identify clinical and
      laboratorial factors associated with the development of arterial or venous
      thrombosis in patients with SLE and lupus nephritis (LN). MATERIAL AND METHODS:
      We reviewed 200 files of patients with SLE and LN to determine if any patients
      had presented a symptomatic episode of thrombosis confirmed by an image study. We
      collected demographic, clinical and laboratory data. Logistic regression was used
      to determine clinical and laboratorial factors associated with thrombotic
      complications. RESULTS: There were 25 thrombotic events in 23 patients, of which
      68% (n = 17) occurred in the venous bed. The overall incidence rate of thrombotic
      events was 29.1 per 1,000 patient-years. The class IV was the most frequent class
      of LN with 40.8% of cases. There were no differences in the distribution of the
      different classes of NL, eGFR, magnitude of proteinuria and markers of lupus
      activity among patients with and without thrombotic complications. In
      multivariate analysis, previous diagnosis of antiphospholipid-antibody syndrome
      (APS) (OR = 126; IC95% 11.3-1419; p < 0.001), serositis (OR = 5; IC95% 0.95-26.9;
      p = 0.05) and history of arterial thrombosis (OR = 24; IC95% 1.8-314; p = 0.01)
      were associated with thrombotic complications and the use of ACE inhibitors
      showed a protective effect (RM = 0.19; IC95% 0.03-0, 98; p = 0.04). CONCLUSIONS:
      Thrombotic complications were frequent in our population. Risk factors related
      with thrombotic complications were a personal history of arterial thrombosis,
      serositis and previous diagnosis of APS. Interestingly, the use of ACE inhibitors
      was associated with reduced risk. We found no greater or lesser risk of
      thrombosis with renal factors such as proteinuria, histological type of LN and
      eGFR.

PMID- 23877807
TI  - Association between depression and higher glucose levels in middle-aged Mexican
      patients with diabetes.
AB  - OBJECTIVE: We report an association between depression and glycemic control in
      patients with type 2 diabetes mellitus (DM-2). MATERIAL AND METHODS: Sixty-five
      diabetic patients (26 men and 39 women) aged 40-60 years were studied within 5
      years of the diagnosis. The patients were assessed using the depression scale
      validated in Spanish, and serum glucose and glycated hemoglobin (HbA1c) levels
      were measured. Pearson's correlation was used to identify associations between
      depression and DM-2 and glycemic control; p < 0.05 was accepted as significant.
      RESULTS: Sex, age, anthropometric measures, and time since the diagnosis of DM-2
      did not differ between patients with and without depression. CONCLUSIONS:
      Patients with depression had higher fasting glucose and HbA1c levels, and these
      levels correlated significantly with the depression score.

PMID- 23877808
TI  - [Phyllodes tumor of the breast: clinicopathologic analysis of 22 cases].
AB  - INTRODUCTION: Phyllodes tumors of the breast are uncommon fibroepithelial
      neoplasms that have potential for recurrence. They are classified as benign,
      borderline, and malignant, based on a constellation of histologic characteristics
      that includes the degree of stromal hypercellularity, cytologic atypia and
      mitotic activity. OBJECTIVE: To analyze the clinical and pathological features of
      22 women treated at a referral center in Mexico City. MATERIAL AND METHODS: We
      performed a retrospective analysis of women with phyllodes tumors of the breast
      treated at our institution between 1998 and 2011. Age, tumor size, surgical
      method, stromal cellular atypia, mitotic activity, stromal overgrowth,
      histological classification and surgical margin status were analyzed to determine
      their possible association with tumor recurrence. RESULTS: Mean patient age at
      presentation was 42 years. Ten of them (43.5%) had late menarche. Six patients
      (27.27%) used hormones. Twenty patients (91%) had tumor detected by self
      examination. Mean size of the lesion was 7.4 cm. Most lesions were located in the
      upper outer quadrant (77.3%) and in the left breast (59.1%). Fourteen patients
      (63.6%) were treated with conservative surgery. Three patients (13.6%) presented
      local recurrence, two as benign tumors and one patient with two recurrences,
      first as benign tumor thereafter as malignant phyllodes tumor at 72 and 108
      months respectively. CONCLUSIONS: . In our study, surgical positive margin status
      is the main prognostic factor for recurrence.

PMID- 23877809
TI  - Morbidity of breast cancer and cervico-uterine cancer in women from the
      occidental region of Mexico.
AB  - BACKGROUND: The incidences of breast cancer (BC) and cervico-uterine cancer (CC)
      vary widely from country to country. In Mexico, BC mortality has doubled in the
      last 20 years to become the second leading cause of death for women aged 30 to 54
      years. CC is the most common cause of death from neoplasia in women over 25 years
      old. In 2006, the state of Nayarit had one of the highest mortality rates for
      these types of cancers in Mexico. OBJECTIVE: To analyze and characterize the
      current demographics and morbidities associated with BC and CC in the state of
      Nayarit. MATERIAL AND METHODS: In this retrospective study, the clinical
      histories of patients who were diagnosed with BC or CC at the State Cancer Center
      from January 2006 to December 2010 were analyzed. RESULTS: A total of 406
      patients with BC and 328 patients with CC were registered. The most common
      clinical stage for both cancer types was IIB. The municipalities of San Pedro
      Lagunillas and El Nayar presented the highest prevalences of BC and CC,
      respectively. CONCLUISION: Our results suggest that women living in poorer and
      more marginalized regions have a higher possibility of developing BC and CC.
      Because BC and CC are preventable and treatable in their early stages,
      demographic information from population records for these cancers is helpful in
      determining the incidence rates and patterns and improving decision-making
      processes.

PMID- 23877810
TI  - [Experience, prevalence and severity of dental caries and its association with
      nutritional status in Mexican infants 17-47 months].
AB  - OBJECTIVE: To determine the experience, prevalence and severity of dental caries
      and its relationship with nutritional status in nursery infants 17 to 47 months
      of age. MATERIAL AND METHODS: A cross-sectional study in 152 infants 17 to 47
      months of age attending one of five day care centers of the city of Pachuca,
      Hidalgo was performed. Clinical examinations were performed using the methods
      recommended by the World Health Organization for epidemiologic studies on dental
      caries. We calculated the caries index (dmft), the significant caries index (SiC)
      as well as the treatment needs index (TNI) and the care index (CI). Nutritional
      status was determined using the weight and height for age, in Federico Gomez's
      scale. In the statistical analysis nonparametric tests were used. RESULTS: Mean
      age was 2.52 +/- 0.76 years; 51.3% were boys. With regard to nutritional status,
      19.1% were classified as malnourished and 19.1% were overweight/obese. The dmft
      index was 1.53 +/- 2.52. The SiC index was 4.14, the TNI 86.3% and the CI 13.7%.
      Caries prevalence was 48.0%. It was observed that 33.5% of children had 1 to 3
      teeth with caries experience and 14.5% had 4 or more teeth affected.
      Statistically significant differences for tooth decay were identified (p < 0.05)
      by age, height and weight but not (p> 0.05) by sex and nutritional status.
      CONCLUSIONS: This study shows that nearly half of children examined had caries
      experience. High treatment needs for dental caries were observed. A correlation
      was found between dmft index and age, weight and height. No association was
      identified between experience, prevalence and severity of dental caries and
      nutritional status of infants. It appears necessary to improve oral health
      preventive measures in these infants.

PMID- 23877811
TI  - [Dental fluorosis prevalence in Mexican localities of 27 states and the D.F.: six
      years after the publication of the Salt Fluoridation Mexican Official
      Regulation].
AB  - OBJECTIVE: To identify the prevalence and severity of dental fluorosis in
      communities located in 28 states of Mexico. MATERIALS AND METHODS: The National
      Dental Caries Survey 2001 (NDCS2001) data base was analyzed. The information of
      26,893 students, ages 12 and 15 years old, of 27 states and the Federal District
      was examined. Dean's dental fluorosis index was applied by standardized
      examiners. The fluorosis prevalence and the Community Fluorosis Index (FCI) were
      calculated. RESULTS: The fluorosis prevalence was 27.9% (95% CI 24.4, 28.5). A
      statistical significance difference in the fluorosis prevalence was observed
      among the states studied (p < 0.0001). The lowest prevalence was detected in
      Morelos (3.2%) and the highest in Durango (88.8%). In 18 (64.3%) of the states
      included more than 90% of the participants showed very mild or lower levels of
      the dental fluorosis index. A low level of the FCI was found in the localities
      belonging to 19 (67.9%) of the states studied (FCI < 0.4). The lowest FCI was
      found in Colima, Yucatan and Morelos. The highest FCI were found in Durango,
      Zacatecas, Aguascalientes and San Luis Potosi (1 <= ICF). This information
      indicates that in these states dental fluorosis is a public health problem.
      CONCLUSIONS: Two-thirds of the states had localities with low prevalence of
      dental fluorosis; however, approximately, one-third of the states investigated
      the fluorosis levels showed the need of a reduction in fluoride exposure among
      the young population.

PMID- 23877812
TI  - Association between selected structural defects and chromosomal abnormalities.
AB  - OBJECTIVE: To determine the association between some major structural
      abnormalities detected prenatally by ultrasound and chromosomal abnormalities.
      MATERIAL AND METHODS: The present study was a retrolective, transversal study. We
      analyzed case records of patients during the fetal follow-up at the Department of
      Maternal Fetal Medicine from January 1994 to May 2010 to identify fetal patients
      with a diagnosis of holoprosencephaly, diaphragmatic hernia, omphalocele, cystic
      hygroma, hydrops and cardiac defects. We analyzed patients who had a prenatal
      invasive diagnosis procedure to obtain the odds ratio (OR) for some major
      isolated anomalies and their different combinations with respect to chromosomal
      abnormalities. RESULTS: We examined 280 patients with ultrasonographic markers
      for chromosomal alteration, 197 met inclusion criteria, from which 88 had
      chromosomal abnormalities. The most frequent diagnosis was trisomy 18 (31.8%),
      which was followed by trisomy 21 (21.6%), trisomy 13 (21.6%), Turner syndrome
      (monosomy X) (14.8%) and other chromosomal abnormalities (10.2%). Among the
      fetuses with nonisolated holoprosencephaly, we obtained an OR of 4.9 95% CI (0.99
      24.2) for aneuploidy. Associated omphalocele had an OR of 7.63 95% CI (2.07
      46.75), p < 0.01. Interestingly, 62% of aneuploidy cases had associated cardiac
      defects [OR = 7.7 95% CI (1.4-41.7)]. In addition, associated cystic hygroma had
      an OR of 2.5 95% CI (0.59-10.91). Heart defects were the most common defects in
      fetuses with trisomy 18 (57.1%), when they were associated with facial cleft, we
      had an OR of 11.08 95% CI (2.99-41.11), p < 0.0001. Statistical potency was
      calculated for each analyzed defect and it was over 80% for all of them but
      diaphragmatic hernia. CONCLUSIONS: The association of 2 or more structural
      defects increased the probability of a fetus to be a carrier of a chromosomal
      disorder; however this was not statistically significative except for associated
      omphalocele. Heart defects showed the greatest association with all chromosomal
      abnormalities. The most important association was among heart defect, facial
      cleft and trisomy 13.

PMID- 23877813
TI  - [Extensively drug-resistant tuberculosis (XDR-TB): successful therapies used in
      the clinic to the disease].
AB  - Mycobacterial species have practically evolved along humankind, sometimes
      provoking serious diseases. Among them, tuberculosis (TB), produced by M.
      tuberculosiscomplex bacteria, is historically the single most devastating
      infectious agent. Like many other microorganisms, M. tuberculosis resistant to
      antibiotics have risen as a consequence of selective pressure for mutants able to
      persist despite being attacked with drugs that would otherwise erradicate them
      from the infected person. Given the current long-term (6-9 months) therapy with
      multiple antibiotics, many people abandon their treatments, therefore promoting
      that bacteria that were not eliminated during therapy get exposed to suboptimal
      antibiotic concentrations, probably leading to mutations and drug resistance. In
      this scenario, extremely-drug resistant (XDR) TB was recognized not more than a
      decade ago, prompting concerns for a more complicated drug regimen with few
      available molecules. In recent years, either old antibiotics have been
      rediscovered as good measures to control XDR-TB, or new ones have emerged as
      alternatives to cure patients of this type of infection. In this work we aim to
      provide the medical community in Mexico with information of such drug regimens
      that have succesfully worked, in order to get their consideration for use in our
      country. 

PMID- 23877814
TI  - [Clinical forum: hypertension in patients with peripheral arterial disease].

PMID- 23877815
TI  - [Strategic planning models at the Instituto Nacional de Ciencias Medicas y
      Nutricion Salvador Zubiran].
AB  - The Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Spanish
      acronym INCMNSZ) is a third tier healthcare facility operated by the Mexican
      Ministry of Health, ando ver the years various strategic planning models have
      been used in its development. This paper present a brief overview of some of
      those strategic planning models and their application and concludes with a
      discussion of the lessons learned and challenges than remain. 

PMID- 23877816
TI  - Challenges in predicting climate change impacts on pome fruit phenology.
AB  - Climate projection data were applied to two commonly used pome fruit flowering
      models to investigate potential differences in predicted full bloom timing. The
      two methods, fixed thermal time and sequential chill-growth, produced different
      results for seven apple and pear varieties at two Australian locations. The fixed
      thermal time model predicted incremental advancement of full bloom, while results
      were mixed from the sequential chill-growth model. To further investigate how the
      sequential chill-growth model reacts under climate perturbed conditions, four
      simulations were created to represent a wider range of species physiological
      requirements. These were applied to five Australian locations covering varied
      climates. Lengthening of the chill period and contraction of the growth period
      was common to most results. The relative dominance of the chill or growth
      component tended to predict whether full bloom advanced, remained similar or was
      delayed with climate warming. The simplistic structure of the fixed thermal time
      model and the exclusion of winter chill conditions in this method indicate it is
      unlikely to be suitable for projection analyses. The sequential chill-growth
      model includes greater complexity; however, reservations in using this model for
      impact analyses remain. The results demonstrate that appropriate representation
      of physiological processes is essential to adequately predict changes to full
      bloom under climate perturbed conditions with greater model development needed. 

PMID- 23877819
TI  - [Editorial].

PMID- 23877820
TI  - [Different cell types in a unilateral multifocal intraocular melanoma].

PMID- 23877821
TI  - [A thirty-four-year-old woman with primary orbital melanoma].

PMID- 23877822
TI  - [Orbital metastasis as primary finding of a typical pulmonary carcinoid].

PMID- 23877823
TI  - [Uveal melanoma: current insights into clinical relevance of genetic testing].
AB  - Uveal melanoma is the most common primary intraocular tumour in Caucasians. There
      are approximately 500 new cases of uveal melanoma in Germany per year and the
      incidence rate peaks at the age of 70 years. Half of all uveal melanoma patients
      develop metastatic disease, which can be observed even many years after
      successful treatment of the primary tumour. In most cases the liver is the
      location of first manifestation. Based on the chromosome 3 status uveal melanomas
      can be divided into two major classes that differ in their metastatic potential.
      Tumours with a high risk to metastasise usually show monosomy 3, whereas tumours
      showing disomy 3 rarely metastasise. If a patient wishes to know about his
      individual risk, prognostic testing of the primary tumour tissue can be performed
      after obtaining tumour material via transscleral or transretinal biopsy, or by
      enucleation. To date results of prognostic testing do not influence therapeutic
      strategies. Recently, major key genes involved in uveal melanoma development,
      GNAQ, GNA11, BAP1, SF3B1 and EIF1AX, have been identified. Mutation profiling, in
      addition to chromosomal 3 analysis, will further refine the classification or
      subclassification of uveal melanomas and will hopefully influence diagnostic or
      therapeutic concepts. Hereditary mutations in tumour suppressor gene BAP1 are
      associated with an increased risk for different tumour entities. Detection of
      germ line mutations in this tumour suppressor gene should implicate further
      general screening examinations of the patient to be able to detect these tumour
      entities. Moreover relatives of these patients should be offered a screening for
      BAP1 mutation. 

PMID- 23877824
TI  - [How is ophthalmic undersupply demonstrated in socially disadvantaged people?
      Cross-sectional pilot investigation on the parametrisation of endpoints for
      patient-centred care research].
AB  - BACKGROUND: Many people depend on additional help to maintain their daily needs.
      In these circumstances preventive medical check-ups are frequently not attended,
      so that disease development may remain undetected until advanced stages or
      correctable disorders may not be treated. A fully anonymised cross-sectional
      study was set up to assess feasibility of parametrisation and to quantify
      sensitive indicators for screening for possible ophthalmic undersupply in
      socially disadvantaged people. METHODS: In 2011 a free, voluntary and anonymous
      ophthalmic examination was offered to attendees of the "Oberhausener Tafel"
      social project. The visual acuity was checked with adjustment of the objective
      refractional error via autorefractor, without or with glasses (if available). In
      addition, an examination of the anterior and posterior segments of the eye was
      done in miosis. As primary endpoint a corrected visual acuity of > 0.5 combined
      with a presenting visual acuity <= 0.5 on the same eye in at least one eye was
      considered. A key secondary endpoint was defined as the absolute deviation of at
      least 1 D in at least one eye between the spherical equivalent measurement of the
      corrective values of the glasses and the autorefractor readings. The primary
      intention of this pilot investigation was to assess the feasibility of this
      endpoint parametrisation and to quantify the corresponding endpoint prevalences.
      RESULTS: Data of 37 participants could be evaluated, 28 of whom brought their
      glasses. The best available visual acuity ranged from 0.12 to 1.3 with a median
      per eye of 0.63. In comparison, the corrected visual acuity per eye was 0.8
      (range 0.32-1.0). In 54 % the presenting visual acuity was one- or both-eyed <=
      0.5, but could be reduced to 30 % (one- or both-eyed) after correction of the
      objective refractional error. In summary, presenting visual acuity in comparison
      to corrected visual acuity showed potential for an at least one-eyed improvement
      for at least two lines in 46 % of the participants. Furthermore, 19 participants
      showed disorders concerning the anterior or posterior eye segment. CONCLUSION: In
      the examined population the visual acuity could be improved by two lines in
      merely 50 % of the participants by adjusting refractive errors. The results
      indicate the need for discussion on how to lower the threshold for attending
      preventive ophthalmic examinations.

PMID- 23877825
TI  - [Poppers-associated maculopathy].
AB  - BACKGROUND: Poppers are a common drug belonging to the alkyl nitrite group and in
      use for several decades. They can be legally purchased for air freshening, but
      are illegal to buy for inhalation. Abuse is associated with maculopathy and
      visual loss as a rare side effect. METHOD: A case series of 27 male, homosexual
      patients with poppers abuse presenting to a single eye clinic in Berlin, Germany,
      is described. Four patients with visual impairment and maculopathy associated
      with the inhalation of poppers were found. RESULTS: Four patients experienced
      subacute visual loss over 2-6 months, one patient can no longer read without a
      magnifying glass. The median age is 40.25 years (28-45 years). Three patients are
      HIV-positive (known since 10-22 years, HAART), a patient is also hepatitis C
      positive. No other ocular and systemic diseases are known. Poppers have been
      inhaled for about 1.5, 12, 15 and 25 years (3-4 */week); all patients have a
      mixed use with the brands Jungle Juice, Rush and Amsterdam. Three patients
      noticed a simultaneous change in colour and shade. Clinical signs on fundoscopy
      ranged from normal foveal appearance to yellowish, dull macula. Optical coherence
      tomography (HD-OCT) showed varying degrees of disruption of the presumed inner
      segment/outer segment (IS/OS) junction; 3 cases bilaterally symmetrical.
      DISCUSSION: Although poppers have been in use for several decades, in 2007 in
      England, the popper composition was changed by law from isobutyl nitrite to
      isopropyl nitrite. It is hard to distinguish whether a specific nitrite group
      triggers the maculopathy or whether it is the dose level, thus suggesting the
      existence of a cumulative dose-response relationship. We postulate that a major
      factor of the manifestation of maculopathy is the individual limit of
      vulnerability. Despite decades of use, the majority of our series does not
      present any pathology. Limits of our patient population represents the HIV
      disease: three maculopathies of our series are HIV-associated and controlled by
      antiretroviral therapy, so that a clear distinction to the disease is absent.
      Poppers were earlier regarded to cause an AIDS-defining disease of viral
      aetiology: Kaposi sarcoma. We are well aware of that association and postulate
      that the observed maculopathies are not causally related to HIV disease and
      antiretroviral therapy. Considering the cultural background of our patients
      (multiple partners, frequent sex) and the disinhibiting effect of poppers, an
      increased risk of HIV disease is found. Since this disease is a rare disorder,
      patients should be asked specifically about poppers abuse. Further study of the
      effect of poppers on maculopathy is needed.

PMID- 23877826
TI  - [The Ophthalmological Organisation of Baden-Wurttemberg--formerly
      Ophthalmological Organisation of Wurttemberg].

PMID- 23877827
TI  - [Leonardo da Vinci and vision].

PMID- 23877828
TI  - [August Gottlieb Richter--reformer of ophthalmology].

PMID- 23877829
TI  - [Basic concepts of optics].

PMID- 23877830
TI  - In silico molecular docking analysis of the human Argonaute 2 PAZ domain reveals
      insights into RNA interference.
AB  - RNA interference (RNAi) is a critical cellular pathway activated by double
      stranded RNA and regulates the gene expression of target mRNA. During RNAi, the
      3' end of siRNA binds with the PAZ domain, followed by release and rebinding in a
      cyclic manner, which deemed essential for proper gene silencing. Recently, we
      provided the forces underlying the recognition of small interfering RNA by PAZ in
      a computational study based on the structure of Drosophila Argonaute 2 (Ago2) PAZ
      domain. We have now reanalyzed these data within the view of the new available
      structures from human Argonauts. While the parameters of weak binding are
      correlated with higher (RNAi) in the Drosophila model, a different profile is
      predicted with the human Ago2 PAZ domain. On the basis of the human Ago2 PAZ
      models, the indicators of stronger binding as the total binding energy and the
      free energy were associated with better RNAi efficacy. This discrepancy might be
      attributable to differences in the binding site topology and the difference in
      the conformation of the bound nucleotides. 

PMID- 23877831
TI  - Extra-pair paternity confirmed in wild white-handed gibbons.
AB  - Knowledge of the genetic mating system of animal species is essential for our
      understanding of the evolution of social systems and individual reproductive
      strategies. In recent years, genetic methods have uncovered an unexpected
      diversity of paternal genetic contributions across diverse animal social mating
      systems, but particularly in pair-living species. In most pair-living birds, for
      example, genetic and behavioral observations have confirmed a previously unknown
      significance of extra-pair copulations (EPCs) and extra-pair paternity. Among
      mammals, white-handed gibbons (Hylobates lar) are also known to live in pairs and
      are traditionally believed to be single-male single-female breeders. However, at
      Khao Yai National Park, Thailand, behavioral observations have confirmed the
      occurrence of both EPCs and functional multi-male grouping, but knowledge about
      the genetic mating system is still unavailable. In this study, we genotyped 89
      white-handed gibbons of the Khao Yai population based on fecal samplings and were
      able to determine paternity for 41 offspring through short tandem repeat
      analysis. We found that females' stable social partners sired the majority
      (90.5%) of offspring (N = 38), while only a few (7.1%) offspring (n = 2 confirmed
      cases; n = 1 inferred case) were conceived with extra-pair partners. The
      paternity of one offspring remained inconclusive (2.4%), because the offspring's
      genotype did not mismatch with the genotypes of two potential sires. Like other
      predominantly pair-living species, gibbons appear to follow a mixed-reproductive
      strategy. The genetic mating system of wild white-handed gibbons is best
      described as flexible, primarily monogamous and opportunistically promiscuous.
      Inc.

PMID- 23877832
TI  - Polymer nitrile N-oxides directed toward catalyst- and solvent-free click
      grafting.
AB  - A general method for the one-pot synthesis of stable polymer nitrile N-oxides was
      developed by a combination of 1,1-diphenylnitroethene with a living anionic
      polymer. The polymer nitrile N-oxide served as a facile and effective grafting
      tool for use with polymers containing unsaturated bonds in a catalyst-free and
      solvent-free [2+3] cycloaddition. 

PMID- 23877833
TI  - Subcortical biophysical abnormalities in patients with mood disorders.
AB  - Cortical-subcortical circuits have been implicated in the pathophysiology of mood
      disorders. Structural and biochemical abnormalities have been identified in
      patients diagnosed with mood disorders using magnetic resonance imaging-related
      approaches. In this study, we used magnetization transfer (MT), an innovative
      magnetic resonance approach, to study biophysical changes in both gray and white
      matter regions in cortical-subcortical circuits implicated in emotional
      regulation and behavior. Our study samples comprised 28 patients clinically
      diagnosed with major depressive disorder (MDD) and 31 non-depressed subjects of
      comparable age and gender. MT ratio (MTR), representing the biophysical integrity
      of macromolecular proteins within key components of cortical-subcortical circuits
      the caudate, thalamic, striatal, orbitofrontal, anterior cingulate and
      dorsolateral regions-was the primary outcome measure. In our study, the MTR in
      the head of the right caudate nucleus was significantly lower in the MDD group
      when compared with the comparison group. MTR values showed an inverse
      relationship with age in both groups, with more widespread relationships observed
      in the MDD group. These data indicate that focal biophysical abnormalities in the
      caudate nucleus may be central to the pathophysiology of depression and critical
      to the cortical-subcortical abnormalities that underlie mood disorders.
      Depression may also accentuate age-related changes in the biophysical properties
      of cortical and subcortical regions. These observations have broad implications
      for the neuronal circuitry underlying mood disorders across the lifespan. 

PMID- 23877834
TI  - Decreased hippocampal volume and increased anxiety in a transgenic mouse model
      expressing the human CYP2C19 gene.
AB  - Selective serotonin reuptake inhibitors, tricyclic antidepressants, various
      psychoactive drugs, as well as endogenous steroids and cannabinoid-like compounds
      are metabolized by the polymorphic cytochrome P450 2C19 (CYP2C19). Absence of
      this enzyme has been recently shown to associate with lower levels of depressive
      symptoms in human subjects. To investigate endogenous functions of CYP2C19 and
      its potential role in brain function, we have used a transgenic mouse model
      carrying the human CYP2C19 gene. Here, CYP2C19 was expressed in the developing
      fetal, but not adult brain and was associated with altered fetal brain
      morphology, where mice homozygous for the CYP2C19 transgenic insert had severely
      underdeveloped hippocampus and complete callosal agenesis and high neonatal
      lethality. CYP2C19 expression was also found in human fetal brain. In adult
      hemizygous mice we observed besides decreased hippocampal volume, an altered
      neuronal composition in the hippocampal dentate gyrus. Reduced hippocampal
      volumes have been reported in several psychiatric disorders, supporting the
      relevance of this model. Here we found that adult hemizygous CYP2C19 transgenic
      mice demonstrate behavior indicative of increased stress and anxiety based on
      four different tests. We hypothesize that expression of the CYP2C19 enzyme
      prenatally may affect brain development by metabolizing endogenous compounds
      influencing this development. Furthermore, CYP2C19 polymorphism may have a role
      in interindividual susceptibility for psychiatric disorders. 

PMID- 23877835
TI  - Ketamine: synaptogenesis, immunomodulation and glycogen synthase kinase-3 as
      underlying mechanisms of its antidepressant properties.
AB  - Major depressive disorder is an extremely debilitating condition affecting
      millions of people worldwide. Nevertheless, currently available antidepressant
      medications still have important limitations, such as a low response rate and a
      time lag for treatment response that represent a significant problem when dealing
      with individuals who are vulnerable and prone to self-harm. Recent clinical
      trials have shown that the N-methyl-D-aspartate receptor antagonist, ketamine,
      can induce an antidepressant response within hours, which lasts up to 2 weeks,
      and is effective even in treatment-resistant patients. Nonetheless, its use is
      limited due to its psychotomimetic and addictive properties. Understanding the
      molecular pathways through which ketamine exerts its antidepressant effects would
      help in the developing of novel antidepressant agents that do not evoke the same
      negative side effects of this drug. This review focuses specifically on the
      effects of ketamine on three molecular mechanisms that are relevant to
      depression: synaptogenesis, immunomodulation and regulation of glycogen synthase
      kinase-3 activity. 

PMID- 23877838
TI  - Electronic and interfacial behavior of gemini metallosurfactants with
      copper(II)/pseudohalide cascade cores.
AB  - In this paper we discuss the newly synthesized binuclear species
      [Cu2(L(PY18))2(MU1,1-N3)2(N3)2] (1) and [Cu2(L(PY18))2(MU1,3-SCN)2(NCS)2] (2), as
      obtained from the monometallic precursor [Cu(L(PY18))Br2]. These gemini
      metallosurfactants incorporate metal/anion cascade cores and are investigated by
      experimental and theoretical methods. Diagnostic IR stretches support the
      presence of MU1,1-bridged (end-on, 2075 cm(-1)) azide groups in 1 and MU1,3
      bridged (end-to-end, 2117 cm(-1)) thiocyanate groups in 2. Anion-to-copper LMCT
      electronic processes at 390 and 440 nm for 1 and at 415 nm for 2 reinforce the
      nature of the metal/anion cascade cores. Both species are redox-active,
      magnetically uncoupled due to poor orbital overlap, and robust in the presence of
      strongly coordinating solvents. At the air-water interface, 1 and 2 yield
      Langmuir films with high collapse pressures of ca. 60 mN m(-1). Domain formation
      is considerably less extensive than that observed for the related monometallic
      precursor and the average molecular areas are in good agreement with their
      modeled molecular size. The resulting Langmuir-Blodgett films are isolated on
      silica substrates and investigated using IR-reflectance/absorbance spectroscopy.

PMID- 23877836
TI  - Targeted silencing of MART-1 gene expression by RNA interference enhances the
      migration ability of uveal melanoma cells.
AB  - Uveal melanoma (UM) is the most common primary intraocular malignancy and the
      leading potentially fatal primary intraocular disease in adults. Melanoma antigen
      recognized by T-cells (MART-1) has been studied extensively as a clinically
      important diagnostic marker for melanoma, however, its biological function
      remains unclear. In the present study, the UM cell line SP6.5, which showed a
      high level of MART-1 expression, was subjected to small interfering RNA-mediated
      silencing of MART-1. Silencing of MART-1 expression increased the migration
      ability of SP6.5 cells and down-regulated the expression of the metastasis
      suppressor NM23. Our results suggest that MART-1 is a candidate target for the
      development of therapeutic strategies for UM and in particular for the
      suppression of metastasis associated with this malignancy. 

PMID- 23877839
TI  - Who owns human genes?: Is DNA patentable?

PMID- 23877837
TI  - Chlamydia pneumoniae infection in atherosclerotic lesion development through
      oxidative stress: a brief overview.
AB  - Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading
      cause of respiratory tract infections and, in the last two decades, has been
      widely associated with atherosclerosis by seroepidemiological studies, and direct
      detection of the microorganism within atheroma. C. pneumoniae is presumed to play
      a role in atherosclerosis for its ability to disseminate via peripheral blood
      mononuclear cells, to replicate and persist within vascular cells, and for its
      pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C.
      pneumoniae infection has been shown to induce the production of reactive oxygen
      species in all the cells involved in atherosclerotic process such as macrophages,
      platelets, endothelial cells, and vascular smooth muscle cells, leading to
      oxidative stress. The aim of this review is to summarize the data linking C.
      pneumoniae-induced oxidative stress to atherosclerotic lesion development. 

PMID- 23877840
TI  - Community psychology and transformative policy change in the neo-liberal era.
AB  - I present ideas about how community psychologists, as researcher-activists, can
      influence public policy. I begin by describing the current neo-liberal era,
      noting the immense obstacles it poses to progressive policy change. Next I
      contrast two approaches to understanding policy formation, evidence-based policy
      and discursive policy analysis, and argue that transformative policy change can
      benefit from both approaches. I then propose three types of policy outcomes that
      community psychology research and activism should aim to promote: (a) shaping
      problem definition, (b) controlling channels for debate and participation, and
      (c) allocating resources. I use examples from community psychologists'
      involvement in policy, mostly in Canada, to illustrate how such policy change can
      be both achieved and constrained. I conclude by discussing implications for
      theory and practice related to policy change.

PMID- 23877841
TI  - Ossification of the petrosphenoidal ligament: unusual variation with the
      potential for abducens nerve entrapment in Dorello's canal at the skull base.
AB  - Variable bony anatomy at the skull base may result in compression or entrapment
      of exiting cranial nerves. The authors present an unusual variation of bilateral
      ossification of the roof of Dorello's canal and review the germane literature.
      Clinicians might consider ossification of the petrosphenoidal ligament (also
      called Gruber's ligament) in patients with unexplained cases of abducens nerve
      palsy.

PMID- 23877842
TI  - Factors influencing measurement of serum iron concentration in dogs: diurnal
      variation and hyperferritinemia.
AB  - We evaluated diurnal variation and hyperferritinemia as factors that influence
      the values of serum iron concentration in dogs, using the International Committee
      for Standardization in Hematology (ICSH) colorimetric method. Serum iron levels
      were significantly higher in the morning than in the evening in 6 clinically
      healthy beagle dogs, and the maximum decrease in serum iron concentration was
      47.3%. Moreover, the change in serum iron concentrations in 22 clinical canine
      cases with various serum ferritin levels was evaluated by immunoprecipitation of
      ferritin. The rate of decline in the serum iron concentrations positively
      correlated with serum ferritin levels (r=0.48, P=0.024). These results show that
      it is necessary to consider the sampling time and serum ferritin level for
      accurate interpretation of serum iron concentrations in dogs. 

PMID- 23877843
TI  - Role of p38 Mapk in development of acute hepatic injury in Long-Evans Cinnamon
      (LEC) rats, an animal model of human Wilson's disease.
AB  - The Long-Evans Cinnamon (LEC) rat, an animal model of human Wilson's disease,
      spontaneously develops fulminant hepatitis associated with severe jaundice at
      about 4 months of age. In this study, we examined the changes in gene expression
      during progression of acute hepatic injury. When levels of gene expression in the
      liver of LEC rats at 13 weeks of age were compared to those in rats at 4 weeks of
      age using oligonucleotide arrays, 1,620 genes out of 7,700 genes analyzed showed
      more than 2-fold differences. Expression levels of 11 of 29 genes related to
      stress-activating protein kinase (SAPK) changed by more than 2-fold in the liver
      of LEC rats, but none of the SAPK-related genes showed changes in expression
      levels in the liver of control rats. Activity of p38 mapk in the liver of LEC
      rats at 13 weeks of age was about 8.1-fold higher than that in rats at 4 weeks of
      age. When LEC rats were administered SB203580, a p38 mapk-specific inhibitor, by
      s.c. injection twice a week from 10 to 13 weeks of age, activities of p38 mapk in
      the liver, activities of AST and ALT and concentrations of bilirubin in sera of
      rats administered SB203580 significantly decreased compared to those in rats not
      administered. These results showed that the increase in activities of p38 mapk
      was related to the occurrence of acute hepatic injury in LEC rats. 

PMID- 23877844
TI  - 15N NMR spectra and reactivity of 2,4,6-triazidopyridines, 2,4,6
      triazidopyrimidine and 2,4,6-triazido-s-triazine.
AB  - 2,4,6-Triazido-s-triazine, 2,4,6-triazidopyrimidine and six different 2,4,6
      triazidopyridines were studied by (15)N NMR spectroscopy. The assignment of
      signals in the spectra was performed using the gauge-independent atomic orbital
      (GIAO)-Tao-Perdew-Staroverov-Scuseria exchange-correlation functional (TPSS)h/6
      311+G(d,p) calculations on the M06-2X/6-311+G(d,p) optimized molecular
      geometries. The Truhlar and coworkers' continuum solvation model called SMD was
      applied to treat solvent effects. With this approach, the root mean square error
      in estimations of the (15)N chemical shifts for the azido groups was just 1.9
      ppm. It was shown that the different reactivity of the alpha- and gamma-azido
      groups in pyridines correlates well with the chemical shifts of the Nalpha
      signals of these groups. Of two nonequivalent azido groups of azines, the azido
      group with the most shielded Nalpha signal is the most electron-deficient and
      reactive toward electron-rich reagents. By contrast, the azido group of azines
      with the most deshielded Nalpha signal is the most reactive toward electron-poor
      reagents.

PMID- 23877845
TI  - Could torasemide be a prophylactic agent of contrast induced acute kidney injury?
      A review about this field.
AB  - Contrast Induced Acute Kidney Injury (CI-AKI), due to the use of contrast media
      in radiographic procedures, is the leading cause of acute renal failure in
      hospitalized patients, and is associated with prolonged in-hospital stay and
      increased morbidity, mortality, and costs. However only peri-procedural hydration
      is now used universally as its preventive strategy. Some studies indicates that
      renin-angiotensin-aldosterone system (RAAS) is possibly responsible for the
      development of contrast-induced nephrotoxicity through mediating abnormalities of
      renal perfusion and other mechanisms. And torasemide, known as loop diuretics,
      could inhibit RAAS through its anti-aldosteronergic function. Therefore,
      speculation about torasemide's prevention of CI-AKI could be firmly made.
      Intravenously administrated torasemide would be promising as a future
      prophylactic agent, possibly in combination with other strategies such as
      adequate peri-procedural hydration and other renal protective agents, in the
      prevention of CI-AKI. In this context, we review the background and the role of
      RAAS on the development of CI-AKI, and discuss the pharmacologic individuality of
      torasemide on RAAS and torasemide's preventive effect on CI-AKI. 

PMID- 23877846
TI  - Investigation of the effects of Enoxaparin, Fondaparinux, and Rivaroxaban used in
      thromboembolism prophylaxis on fracture healing in rats.
AB  - BACKGROUND: Today, there is a small number of studies on the effects of
      Enoxaparin and Fondaparinux used commonly in the prevention of venous
      thromboembolism on healing of fracture cases. AIM: The aim of this study was to
      investigate clinically, radiologically and histopathologically, the effects of
      Enoxaparin, Fondaparinux and Rivaroxaban used in thromboembolism prophylaxis on
      fracture healing in a rat model of femur fracture. MATERIALS AND METHODS: Thirty
      two male Sprague Dawley rats were randomized into four groups (n=8): the control
      group (Group 1), the Enoxaparin group (Group 2), the Fondaparinux group (Group
      3), and Rivaroxaban group (Group 4). Under general anesthesia, a standard closed
      fracture was created in the left femur of each rat using an osteotome. Group 1
      was given saline solution (1 cc/day, sc), Group 2 Enoxaparin (100 anti Xa
      IU/kg/day, sc), Group 3 Fondaparinux (0.2 mg/kg/day, sc), and Group 4 Rivaroxaban
      (3 mg/kg/day, po) for 21 days. After all rats were sacrificed at the end of day
      21, their left femurs were disarticulated at the level of the hip and knee. The
      bony union was radiologically, clinically, and histopathologically evaluated.
      RESULTS: No differences were found between the groups in terms of clinical,
      radiological, and histopathological findings in fracture healing (p = 0.849, p =
      0.731, and p = 0.395, respectively). CONCLUSIONS: Enoxaparin, Fondaparinux and
      Rivaroxaban used in thromboembolism prophylaxis cause no significant changes in
      fracture healing with short term follow up. Thus, they can be safely used in
      cases of fractures.

PMID- 23877847
TI  - Role of adenosine receptors in the anti-nociceptive effects of allopurinol in
      mice.
AB  - BACKGROUND: Inhibition of xanthine oxidase by allopurinol increases hypoxanthine
      and xanthine, which are converted to purines, including the inhibitory
      neuromodulator adenosine. AIM: We aimed to investigate the antinociceptive
      effects of allopurinol in thermal and chemical pain models in mice and to
      evaluate its possible antinociceptive mechanism by using selective adenosine
      receptors A1, A2A antagonists in mice. MATERIALS AND METHODS: Sixty four adult
      male mice were used. Mice received an intraperitoneal injection of vehicle or
      allopurinol (50-200 mg/kg). Assessment of antinociceptive effects and locomotor
      activity were performed in three models of acute pain; a thermal model and two
      chemical model. RESULTS: Allopurinol presented dose-dependent antinociceptive
      effects in all models with no obvious motor deficits. The opioid antagonist
      naloxone did not reverse these effects. The selective A1 antagonist, DPCPX, and
      the selective A2A antagonist, ZM241385, completely prevented allopurinol-induced
      antinociception. CONCLUSIONS: Allopurinol-induced antinociception may be related
      to adenosine accumulation. Allopurinol seems to be well tolerated with no
      locomotor side effects at high doses and it may be useful to treat pain
      syndromes.

PMID- 23877848
TI  - HS N-sulfation and iduronic acids play an important role in the infection of
      respiratory syncytial virus in vitro.
AB  - BACKGROUND: As a member of Glycosaminoglycans (GAGs), heparan sulfate (HS) are
      sulfated to varying extents and used by a large number of viruses to initiate
      infection, including respiratory syncytial virus (RSV). Heparinases I, II, III
      can remove N-sulfation and iduronic acids units of HS, and low-molecular-weight
      heparin (LMWH) has a very similar structure to that of HS. AIM: The tropism of
      RSV for different cell lines and the efficiency of Heparinases and LMWH in
      inhibiting RSV infection were estimated in this study. MATERIALS AND METHODS:
      Hela, Hep-2, HEK293 and Lo2 cell lines were pretreated with heparinases I, II,
      III and LMWH, and the cells were infected by RSV in vitro. RSV infectivity was
      determined by flow cytometry and western-blot. RESULTS: All cells were
      susceptible to RSV except Lo2. Heparinases I, II, III and LMWH treatments reduced
      the susceptibility of Hep-2 cells to RSV infection. For HEK-293 heparinase II and
      III treatment could reduce RSV infection. All enzymes could not change the
      susceptibility of Hela cells to RSV infection. CONCLUSIONS: These findings
      suggest that the heterogeneity of HS especially for rich N-sulfation and iduronic
      acids may play an important role in RSV infection in some mammalian cells.

PMID- 23877849
TI  - Effects of estrogen, estrogen/progesteron combination and genistein treatments on
      oxidant/antioxidant status in the brain of ovariectomized rats.
AB  - INTRODUCTION: The aim of this study was to investigate the antioxidative effects
      of estradiol (E), E plus progesteron (P) combination (E/P) and genistein (G)
      treatment in the brain of ovariectomized (OVX) rats. MATERIALS AND METHODS: Adult
      female Sprague-Dawley rats were divided into five groups, with each group
      including ten rats. Rats were anesthetized and bilateral ovariectomy was
      performed under general anaesthesia in all groups except for the sham operation
      group. Groups included: Sham-operated, control (OVX), estrogen treated group
      (OVX+ E), E/P combination group (OVX+E/P) and G treated group (OVX+G). Treatments
      were applied for 8 weeks. The total anti-oxidant status (TAS), total oxidant
      status (TOS), nitric oxide level (NO), glutathione peroxidase activity (GSH-Px)
      and oxidative stress index (OSI) were analysed in the brain tissue of rats from
      each treatment category. RESULTS: Ovariectomy lead to an increase in brain TOS
      and OSI levels compared to the sham group (p < 0.05). Also, ovariectomy resulted
      in a decrease in brain TAS levels compared to the sham group that approached
      statistical significance (p = 0.078). Significant decreases in TOS, OSI, GSH-Px
      and a significant increases in TAS and NO levels were observed in the E-treatment
      group compared to the control group (p < 0.001). The E/P combination group
      exhibited a significantly decreased TOS and OSI and significantly increased TAS
      and NO levels relative to the control group (p < 0.05). Genistein treatment
      resulted in a significant decrease in TOS and OSI compared to the control group
      (p < 0.05). CONCLUSIONS: Oxidative stress markers increase in the brain tissue of
      OVX rats. Conversely, estradiol, E/P and G supplementation decreases oxidative
      stress markers and increases antioxidant activity. Using G may prevent neural
      pathologies result in menopause-related oxidative stress.

PMID- 23877850
TI  - Tissue-specific modification of clock methylation in aging mice.
AB  - BACKGROUND: Circadian rhythms tend to change as animals age; however, the
      molecular mechanisms underlying these are not yet fully understood. OBJECTIVE: To
      investigate whether the DNA methylation of clock genes changes with age and
      contributes to circadian dysfunction in aged animals. METHODS: We examined the
      methylation of clock promoters in the stomach, kidney, striatum, and spleen by
      using a methylation-specific polymerase chain reaction (MSP) assay. RESULTS: Our
      results show that different tissues exhibit specific patterns of clock
      methylation. Additionally, methylation frequency decreased significantly in older
      mice at the Per1 promoter in the stomach, but it was significantly increased in
      older mice at the Cry1, Bmal2, and Npas2 promoters in the spleen. CONCLUSION: The
      findings from our study suggest that DNA methylation contribute to age-related
      changes in circadian rhythms in certain slave oscillators.

PMID- 23877851
TI  - Antihemolytic activity and mineral contents of Juglans regia L. flowers.
AB  - OBJECTIVES: Juglans (J.) regia L. is known to possess many biological properties.
      In this study, antihemolytic activity of methanol extract of Juglans regia L.
      flower were investigated. MATERIALS AND METHODS: Antihemolytic activities of
      Juglans regia L. flowers were evaluated by various in vitro assays. In addition,
      scavenging of hydrogen peroxide and mineral contents of flowers were determined
      using atomic absorption spectroscopy. RESULTS: Extract showed good antihemolytic
      activity against H2O2 and CuOOH induced hemolysis in comparison with control.
      Extract was capable of scavenging H2O2 in a concentration dependent manner. IC50
      for H2O2 scavenging activity was 311+/-12.8 ug ml-1. The amount of eight elements
      was determined and was in the order: Mn > Cu > Fe > Zn. CONCLUSIONS: Our study
      indicate that J. regia flower has remarkable antihemolytic activity, which maybe
      result of its high phenol and flavonoid contents, especially quercetin.

PMID- 23877852
TI  - Predictors of hypertension control in Turkey: the MELEN study.
AB  - BACKGROUND: Hypertension is one of the most common causes of atherosclerosis,
      morbidity and mortality in adults. A total of 11 million hypertensive patients
      were estimated in Turkey. AIM: The aim of this study was to investigate the
      prevalence, awareness and control of hypertension in Duzce and compare the
      current data with the literature. MATERIALS AND METHODS: The visits were carried
      out in May and June, 2010 in Yigilca town health centre on 2298 participants
      (1471 female, 827 male with a mean age of 50). Data were obtained by a simple
      form, physical examination and sampling of blood. Hypertension was defined as a
      blood pressure 140 mmHg and/or 90 mmHg, and/or use of antihypertensive
      medication. The data of patients under control were compared with the patients
      who were not under control. RESULTS: Hypertension was detected in 964
      participants. General prevalence was 42%. Hypertension awareness ratio was 70%,
      use of antihypertensive medication was 39% and the ratio of patients under
      control was 28%. Antihypertensive drug use, age and awareness were lower in the
      uncontrolled group. Logistic regression analysis revealed that only
      antihypertensive drug use and BMI < 30 were the independent predictors of
      hypertension under control [Odd's ratio (OR) = 3.43; 95% confidence interval (CI)
      = 2.54-4.64, p < 0.001 and OR = 1.69; 95% CI = 1.23- 2.32, p = 0.01;
      respectively]. CONCLUSIONS: Hypertension is one of the most important public
      health problems in Turkey. According to the literature data the awareness of
      hypertension was increased significantly in the last five years. On the other
      hand, control ratio was increased very little compared with the previous studies.

PMID- 23877853
TI  - The HUGE formula (hematocrit, urea and gender): association with cardiovascular
      risk.
AB  - OBJECTIVES: To evaluate the relationship between chronic renal failure (CFR)
      defined through HUGE (hematocrit, urea and gender) formula score and the
      patient's cardiovascular risk measured through cardiovascular disease antecedents
      such as ischemic cardiopathy, cerebrovascular disease and peripheral arterial
      disease. DESIGN AND METHODS: The sample consisted of 2,831 subjects. Mean age was
      51.2+/-14.7 years and 53.5% were female. Serum creatinine, urea, hematocrit and
      24h proteinuria were analyzed. HUGE score was calculated from gender, urea and
      hematocrit. GFR was estimated from uncalibrated serum creatinine using the
      abbreviated Modification of Diet in Renal Disease equation (MDRD-4). UAE was
      measured in first morning urine sample. RESULTS: Using HUGE formula 2.2% (n = 61)
      of subjects had CRF. Of them, 12 (19.7%) had cardiovascular disease history.
      Among patients without CRF (n = 2770), 194 subjects had history of previous
      cardiovascular diseases (0.07%; p < 0.001 Square Chi test). Using the MDRD-4
      formula 4.0% of subjects (n = 113) had a GFR < 60 ml/min. Of them, 18 (15.9%) had
      cardiovascular disease history. Among patients without CRF (n = 2718), 188
      subjects had history of previous cardiovascular diseases (0.07%; p < 0.001 Square
      Chi test). Odd's ratio for cardiovascular diseases using HUGE definition of CRF
      was 3.25 (p = 0.001, Mantel-Haenszel test). CFR was associated to higher pulse
      pressure (PP) and increased urinary albumin excretion. CONCLUSIONS: A significant
      cardiovascular risk was associated to the diagnosis of CRF through HUGE formula.
      This relation was closer than the obtained using MDRD estimated GFR in spite of a
      bigger sample. HUGE formula seems to be a useful tool for diagnosing CRF and
      evaluate the cardiovascular risk of these patients.

PMID- 23877854
TI  - Early postoperative hemodynamic performances of stented versus stentless aortic
      xenografts in aortic valve replacement in elderly patients: a comparative study.
AB  - BACKGROUND AND AIM: Surgical valve replacement is the most commonly performed for
      aortic stenosis. Randomized trials comparing stentless to stented bioprostheses
      for aortic valve replacement in elderly are scarce. The aim of our study was
      comparing and evaluating the early hemodynamic performances of HancockTM stented
      and FreeStyleTM stentless xenograft aortic valves in aortic valve replacement in
      elderly patients. PATIENTS AND METHODS: The study involved 40 patients (27
      females and 13 males) older than 75 years old. The study was done during the
      postoperative period. Aortic valve replacements of stented and stentless
      xenografts were performed to the patients in Group I and Group II, respectively.
      Investigations for the echocardiographic results were completed on the
      postoperative 8-10th days. Parameters for the evaluation of hemodynamics were
      peak pressure gradient, mean pressure gradient and effective orifice area. The
      parameters were calculated with Doppler echocardiography by using specific
      formulas. RESULTS: Peak pressure gradients in patients with stented valves were
      significantly higher than in stentless valves [Stented valve group 32.45 +/- 7.58
      vs Stentless valve group 21.50 +/- 4.77 mmHg] (p < 0.05). Mean pressure gradients
      were found to be significantly higher in stented group compared with stented
      group [Stented valve group 11.050 +/- 3.2521 vs Stentless valve group 19.350 +/-
      6.6036 mmHg] (p < 0.05). The effective orifice area index of implanted valve was
      significantly greater in the stentless group, as well [Stentless valve group
      2.5050 +/- 0.6022 vs Stented valve group 1.3050 +/- 0.3316 cm2] (p < 0.05).
      CONCLUSIONS: In early postoperative period, effective orifice areas and pressure
      gradients were found higher in stentless valve group.

PMID- 23877855
TI  - The predictors of poor outcomes in patients with femoral artery injuries.
AB  - PURPOSE: This study investigated the predictors of poor outcomes, including limb
      loss and death, in patients with femoral artery injuries. PATIENTS AND METHODS:
      The study included 158 patients aged 2-82 (mean age 28.4 +/- 16.5) with femoral
      arterial injury (common, deep, and superficial femoral artery) that were treated
      surgically between 2000 and 2010. Isolated venous injuries were excluded.
      Demographic and clinical data of the patients, including age, gender, admission
      time, pulse rate and blood pressure, hematocrit value, reason of injury,
      associated injury, and Mangled Extremity Severity Score (MESS) were recorded.
      RESULTS: Of the 158 patients, the death and amputation rates were 5.7% (9) and
      5.1% (8), respectively. In logistic regression analysis, four variables (pulse
      rate, MESS, hematocrit, and bone trauma) were found to be independent predictors
      for poor outcomes. The Odd's ratios and confidence interval values of these
      variables were as follows: 7.24 (1.94-26.92), 21.75 (5.41-87.48), 5.93 (3.04
      11.54) and 7.46 (2.09-9.56), respectively. CONCLUSIONS: The MESS value, presence
      of bone fracture, hematocrit, and pulse rate on admission are predictive risk
      factors for poor outcomes in patients with femoral artery injury. Therefore, in
      these patients, prompt intervention by experienced surgeons is crucial for limb
      salvage and decreased mortality.

PMID- 23877856
TI  - Pathway analysis detect potential mechanism for familial combined hyperlipidemia.
AB  - BACKGROUND: Familial combined hyperlipidemia (FCHL) is the most commonly
      inherited hyperlipidemia in men. It constitutes a substantial risk factor for
      atherosclerosis patients. AIM: To delineating the potential mechanism of FCHL by
      bioinformatics tools. MATERIALS AND METHODS: In this study, Protein-Protein
      Interaction (PPI) network was constructed to identify the potential functional
      proteins and their interactive relationships in familial combined hyperlipidemia.
      RESULTS: Our results showed that androgen receptor (AR) might play an important
      role in familial combined hyperlipidemia by interaction with TGIF1, NR3C1, KLK2,
      etc. Some pathways were also identified, such as Hedgehog signaling pathway,
      Phosphatidylinositol signaling system, and Long-term depression, which were all
      demonstrated participating in lipid metabolism in previous experiments.
      CONCLUSIONS: Although lack of direct evidence, by PPI network construction it
      proved AR is a key factor in FCHL, and also demonstrated that PPI network
      construction is an alternative avenue for FCHL analysis.

PMID- 23877857
TI  - Evaluation of insulin resistance, tumor necrosis factor alpha, and total
      antioxidant status in obese patients smoking cigarettes.
AB  - INTRODUCTION AND BACKGROUND: Obesity and smoking are leading causes of morbidity
      and mortality worldwide. Cross-sectional studies indicate that heavy smoking may
      be associated with a greater risk of obesity. While there are important
      unresolved issues in relation to the effect of smoking on body weight, there is
      increasing evidence that smoking is conducive to a greater accumulation of
      visceral fat and greater insulin resistance. AIM: of this study was to determine
      the potential influences of obesity and smoking on tumor necrosis factor alpha
      (TNF-alpha), total antioxidant status (TAS), and insulin resistance. SUBJECTS AND
      METHODS: 30 obese nonsmokers, 30 obese smokers, 30 normal-weight smokers, and 30
      healthy volunteers (the control) were studied. In all subjects, assessments of
      TNF-alpha, TAS, and insulin were made. Insulin resistance was evaluated according
      to the homeostasis model assessment-insulin resistance (HOMA-IR) protocol.
      RESULTS: TNF-alpha concentrations, as well as insulin resistance levels, in obese
      patients significantly exceeded those observed in the control. Compared to the
      control, obese patients presented significantly lower TAS levels. In the group of
      obese patients who actively smoked cigarettes, further increases in TNF-alpha and
      insulin resistance, as well as decreases in TAS level, were noticed. TNF-alpha
      concentration and insulin resistance levels were significantly higher, while TAS
      was lower in normal-weight smoking subjects, compared to the control. A positive
      correlation between TNF-alpha and HOMA-IR was found in the overall population.
      CONCLUSIONS: Obesity may evoke inflammatory processes, oxidative stress, and
      insulin resistance, all of which are aggravated by cigarette smoking. TNF-alpha
      should be considered in the complex pathogenesis of insulin resistance in obese
      patients who actively smoke.

PMID- 23877858
TI  - Integration microarray and regulation datasets for Chronic Obstructive Pulmonary
      Disease.
AB  - BACKGROUND: Pulmonary disease has become one of the major health problems. AIM:
      To investigate the regulation mechanism of Chronic Obstructive Pulmonary Disease
      (COPD) on gene expression and pathway level. MATERIALS AND METHODS: We mapped the
      differentially expressed genes to a regulation network and pathways, using
      transcriptome profiles and regulation data. We constructed a TF-target gene
      regulation network, TF-pathway regulation network, and pathway crosstalk network.
      RESULTS: STAT1, NFKB1, SMAD4, and STAT3 played an important role in COPD through
      participating in a number of pathways. Although these related pathways all have
      been demonstrated associated with COPD in previous reports, the detail mechanism
      may be not very clear. CONCLUSIONS: Our results may help to further understanding
      the mechanism of COPD. And Identified multiple pathways will also provide novel
      avenues in the treatment of COPD.

PMID- 23877859
TI  - Glucose and arterial blood pressure variability in Obstructive Sleep Apnea
      Syndrome.
AB  - INTRODUCTION: Current evidence supports an association between Obstructive Sleep
      Apnea Syndrome (OSAS), insulin resistance, type 2 diabetes mellitus (DM) and
      cardiovascular disorders. The relationship is complex and still remains poorly
      understood. AIM: The aim of this study was to examine the potential correlation
      of sleep characteristics with glucose and arterial pressure values variability in
      non - diabetic, non-hypertensive patients with OSAS. SUBJECTS AND METHODS: We
      examined 22 subjects, 11 men and 11 women (mean age 54 +/- 14,5 years), recently
      diagnosed with OSAS (Apnea - Hypopnea Index (AHI) >= 5 apneas/hypopneas per hour
      of sleep) by full night polysomnography (PSG). Fasting and postprandial after a 2
      hour oral glucose tolerance test (OGTT) glucose and insulin levels were measured,
      and homeostatic model assessment of insulin resistance (HOMA(IR)) index profile
      as well as Matsuda insulin sensitivity index (ISI) were calculated. A 24 hour
      glucose monitoring with subcutaneous measurements every 5 minutes and a 24-hour
      arterial blood pressure (ABP) monitoring (Holter monitoring) were evaluated.
      RESULTS: AHI, a widely accepted marker of the severity of OSAS, was correlated
      with HOMA and Matsuda index (p = 0.016 and p = 0.022, respectively), Standard
      Deviation (SD) of glucose measurements (p = 0.05) and mean diastolic blood
      pressure (p = 0.007). Percentage of sleep time with saturation of hemoglobin with
      oxygen, as measured by pulse oximetry, (SpO2) < 90% was also correlated with HOMA
      and Matsuda index (p = 0.014 and p = 0.012, respectively), coefficient of
      variation (CV) of glucose measurements (p = 0.009) and SD of 24-hour systolic
      blood pressure. Moreover, minimum SpO2 was correlated with glucose levels (p =
      0.018), Matsuda index (p = 0.30) and SD of 24-hour diastolic and systolic blood
      pressure (p = 0.005 and p = 0.022, respectively). CONCLUSIONS: Glucose and
      arterial pressure variability were associated with markers of OSAS severity (AHI,
      % sleep time with SpO2 < 90%, min SpO2), among nondiabetic patients. Thus,
      glucose and arterial pressure variability in OSAS may be an additional marker of
      cardiovascular risk as well as of future diabetes in these subjects.
      Nevertheless, the clinical significance of our observations remains to be
      confirmed by prospective studies.

PMID- 23877860
TI  - LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression
      leading to vitamin D consumption and hypovitaminosis D in HIV-infected
      individuals.
AB  - AIM: Vitamin D deficiency is very common among HIV-infected subjects. We cross
      sectionally evaluated the prevalence and risk factors for hypovitaminosis D in 91
      HIV-infected Italian patients. PATIENTS AND METHODS: We studied in a cohort of 91
      HIV-infected Italian patients the metabolism of Vitamin D by evaluating the in
      vitro expression of CYP27B1, CYP24A1 and vitamin D receptor (VDR) by monocytes
      and macrophages stimulated with the viral envelope protein gp120 or
      lipopolysaccharide (LPS). RESULTS: The prevalence of vitamin D deficiency (25OHD
      < 10 ng/ml) and vitamin D insufficiency (25OHD 10-30 ng/ml) was 31% and 57%,
      respectively. In univariate analysis, female sex (p = 0.01), increasing age (p =
      0.05), higher highly sensitive-C reactive protein (p = 0.025), higher parathyroid
      hormone (PTH) (p = 0.043) and lower BMI (p = 0.04) were associated with vitamin D
      deficiency. In multivariate analysis, the association was still significant only
      for PTH (p = 0.03) and female sex (p = 0.03). Monocyte stimulation with LPS (100
      ng/ml) or gp120 (1 ug/ml) significantly upregulated CYP27B1 mRNA expression.
      Moreover, gp120 significantly increased VDR mRNA levels. On the contrary, neither
      LPS nor gp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100
      ng/ml) significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When
      monocytes were cultured in the presence of 25OHD (40 ng/ml) and stimulated with
      LPS we detected significantly lower levels of 25OHD in the supernatant.
      CONCLUSIONS: Vitamin D deficiency was very common in our cohort of HIV-infected
      patients. Chronic inflammation, including residual viral replication, may
      contribute to hypovitaminosis D, by modulating vitamin D metabolism and
      catabolism. Systematic screening may help identifying subjects requiring
      supplementation.

PMID- 23877861
TI  - Anatomical reconstruction of donor site after large iliac crest graft harvest
      with equivalent iliac crest allograft. A prospective controlled study.
AB  - BACKGROUND: Iliac bone graft harvesting is a common procedure in spinal surgery
      and trauma center for spinal fusion and nonunion of the extremities. AIM,
      PATIENTS AND METHODS: To compare the pain and cosmetic outcomes of patients
      undergoing iliac crest anatomical reconstruction using equivalent iliac crest
      allograft (R group) with those of patients without reconstruction of the iliac
      crest defect (NR group), a prospective nonrandomized controlled study was
      conducted. RESULTS: In R group, the intensity and prevalence of pain were
      significantly lower than those in NR group. Cosmetic outcome and satisfaction
      score were also significantly improved in R group. One patient of R group
      suffered from lipolysis and superficial infection which healed by regular
      dressing change for two weeks. There were no cases of allograft displacement,
      implant loosening, internal fixation breakage or immunological rejection. Seven
      patients in NR group had significant pain related to the tenting of skin over the
      defect. Radiologic incorporation of pelvis was documented in all patients except
      four having partial re-sorption of the allograft. Early fibrous healing and the
      late creeping substitution were noted in all patients of R group. CONCLUSIONS:
      Equivalent iliac crest allograft provides an effective alternative for iliac
      crest anatomical reconstruction, leading to reduced donor site pain and better
      cosmesis.

PMID- 23877862
TI  - Influence of PRF in the healing of bone and gingival tissues. Clinical and
      histological evaluations.
AB  - INTRODUCTION: The healing of bone tissues around dental implants is based
      primarily on a correct osseointegration. BACKGROUND: Typically, implants
      stability and peri-implant tissues health are anticipated to decrease during the
      early weeks of healing; this is followed by an increase in stability. AIM: The
      aim of the present study is to assess a predictable protocol in order to increase
      the peri-implant tissues maintenance around post-extractive dental implants,
      thanks to the use of Platelet-Rich Fibrin (PRF) membrane. MATERIALS AND METHODS:
      This is a retrospective observational study of 127 tapered dental implants placed
      in the immediate post-extraction sites of maxillary bone of 59 patients.
      Atraumatic dental extraction and flapless implant surgery was performed in all
      reported cases. The cortical bone position relative to the implant reference
      point was evaluated at implant placement and 10 to 24 months following
      implantology. The gap between bone tissue and the implant surface was measured up
      to a maximum of 3 mm. After placing implants we have filled the surgical site
      with a PRF gel, so as to fill the gap between bone tissue and the implant
      surface, and then we have covered the surgical site with a PRF membrane, so as to
      coat the gap between the alveolar crest and the implant. RESULTS: In all cases,
      we observed the complete covering of the dental implants, with newly formed soft
      tissue of variable thickness between 1 and 3 mm. Cortical bone adaptation from
      the time of implant placement up to 30 months following prosthetic restoration
      ranged from 0.4 mm to 1.7 mm. CONCLUSIONS: Our study showed a series of
      successful rehabilitations, with post-extraction implantology technique, in 99.8
      percent of cases, despite the success rates in the medium and long-term post
      extraction implantology reported in the literature range between 92.7 percent and
      98.0 percent. Long-term maintenance of crestal bone and the rapid healing of soft
      tissue dimension with maintenance of peri-implant papilla were observed as
      outcomes after post-extractive implants insertion.

PMID- 23877863
TI  - Tongue musculomucosal flap for soft palate reconstruction in patients with OSAHS 
      clinical experience in technical strategy.
AB  - BACKGROUND: With the idea of "replacing lost tissure with similar tissure in
      kind", vessel-pedicled palate mucosal flap, pedicled buccal musculomucosal flap
      and adjacent tongue musculomucosal flap could be the ideal approaches to soft
      palate reconstruction. AIM: To assess the adjacent tongue musculomucosal flap for
      soft palate reconstruction. PATIENTS AND METHODS: From August 2010 to July 2011,
      we applied tongue musculomucosal flap for soft palate reconstruction in three
      patients with Obstructive Sleep Apnoea/Hypopnoes Syndrome (OSAHS) in order to
      release OSAHS symptom by glossal volume reduction. RESULTS: All patients
      recovered from intraoral operations with good objective as subjective speech and
      swallowing. Suffice it to say that OSAHS symptom was released for these patients.
      CONCLUSIONS: Here we provide a case to deal with problems related to OSAHS
      symptom when one works on oral surgery or reconstructing oral structure.

PMID- 23877864
TI  - Remifentanil without muscle relaxants for intubation in microlaryngoscopy: a
      double blind randomised clinical trial.
AB  - OBJECTIVES: We aimed to compare the effect of remifentanil without muscle
      relaxant with succinylcholine for intubation in microlaryngoscopy. PATIENTS AND
      METHODS: Eighty patients were randomly divided into two groups: Group R (n=40)
      and S (n=40) received remifentanil 4 ug/kg intravenously or 1 ug/kg respectively.
      Anesthesia was induced with 2 mg/kg propofol in both groups. Intubation was
      performed after bolus administration of 10 ml saline as a placebo or 1 mg/kg of
      succinylcholine in Group R and S respectively. Remifentanil infusion was
      initiated at 0.025 MUg/kg in each groups. RESULTS: Intubation conditions were
      similar in both groups. The mean arterial pressure (MAP) values at post-induction
      period were significantly lower in the Group S than in the Group R (p = 0.001).
      The requirement for ephedrine in Group R was found to be significantly lower than
      Group S (p = 0.023). Recovery times were significantly shorter (p = 0.001) and
      recovery scores were significantly higher (p = 0.021) in Group R. Time to patient
      could respond to commands was significantly longer in the Group S (p = 0.001).
      The surgeon's satisfaction score was significantly higher in Group R (p = 0.001).
      CONCLUSIONS: It was concluded that remifentanil without muscle relaxants provides
      similar intubating conditions as that provided by succinylcholine, and
      remifentanil is superior to succinylcholine with regard to haemodynamic stability
      and recovery duration.

PMID- 23877865
TI  - Anesthetic management of totally robotic right lobe living-donor hepatectomy: new
      tools ask for perioperative care.
AB  - Living donor transplantation is an accepted clinical practice in select
      transplant centers in Western countries to increase the availability of organs,
      while is standard practice in East Asian transplant programs. Living-donor right
      hepatic lobe resection is a particularly risky operation, with two mandatory
      outcomes: no serious complications for the donor, and an optimal graft-recipient
      body weight ratio. The use of robotic surgery has increased worldwide thanks to
      its minimally invasive approach, and is now becoming suitable for living donor
      procurement. From the anesthetic point of view, robotic surgery reveals itself to
      be extremely challenging, and requires diverse capacities in teamwork and
      planning of anesthetic management. We report what we believe is the first case of
      anesthetic management of a totally robotic right lobe resection in a living
      donor, and describe the steps taken by the anesthetists, in concert with the
      surgical team, to ensure delivery of the safest patient care. 

PMID- 23877866
TI  - Respiratory failure and pharyngeal hematoma as presenting signs of Moschcowitz's
      syndrome: a case report and literature review.
AB  - Moschcowitz's syndrome or thrombotic thrombocytopenic purpura is a quite rare
      pathology in childhood, being, as a matter of fact, more frequent among adult
      people. Often it is hard to distinguish from other pathologies in children both
      for its rare incidence and for the presence of clinical forms that are very
      heterogeneous and difficult to be classified. We report on a 13 year-old girl
      suffering from Moschcowitz's syndrome, in whom respiratory failure and pharyngeal
      hematoma were the first sign of the disease follone by jaundice, hematoma of the
      arm and limbs. The girl was treated with plasmapheresis with an improvement of
      her general condition. Since then we have followed up the girl for two years
      without any reappearance of the symptomatology. To our knowledge this is the
      first report of this peculiar presentation in children. 

PMID- 23877867
TI  - Potential advantages of simvastatin as a novel anti-vitiligo arsenal.

PMID- 23877868
TI  - Application of POLARICTM fluorophores in an in vivo tumor model.
AB  - Fluorescent and luminescent tools are commonly used to study the dynamics of
      cancer progression and metastases in real-time. Fluorophores have become
      essential tools to study biological events. However, few can sustain fluorescence
      long enough during long-term studies. In the present study, we focused on a
      series of new amphiphilic fluorophores known as POLARICTM, which emit strong
      fluorescence in lipid bilayers and can be readily modified using the Suzuki
      Miyaura cross-coupling reaction. Appropriate chemical modifications of
      substituent groups can improve target-site specificity, reduce cytotoxicity and
      prolong emission. Therefore, in contrast to conventional fluorescent probes,
      these fluorophores show promise for long-term monitoring of biological processes.
      In the present study, we conducted long-term observations of tumor growth and
      metastasis using a POLARIC derivative as a novel fluorescent probe. For this
      purpose, we studied the metastatic melanoma cell line A375-SM, which proliferates
      at a high rate. We compared the characteristics of the POLARIC probe with the
      commercially available fluorescent dye PKH26 and fluorescent protein mRFP1. A375
      SM cells were labeled with these fluorescent probes and orthotopically implanted
      into nude mice. The fluorescence emitted by POLARIC was detected more than five
      weeks after implantation without causing detectable harmful effects on tumor
      growth. By contrast, fluorescence of cells labeled with PKH26 could not be
      detected at this same time. Furthermore, POLARIC-, but not PKH26-labeled cells,
      were also detected in lung metastases. These results indicate that labeling cells
      with POLARIC fluorophores can significantly extend the time course of in vivo
      studies on tumor cell growth.

PMID- 23877870
TI  - Reference intervals of bone turnover markers determined by using their curve
      fitting valley for adult females in China.
AB  - SUMMARY: The reference values for bone turnover markers (BTMs) have a significant
      role in the diagnosis, monitoring, and treatment of metabolic bone disease. This
      study proposes that the peak value of bone mineral density and the trough value
      for the BTM curve can be used to determine the reference range of BTM.
      INTRODUCTION: The aim of this study is to determine the reference intervals of
      BTMs for adult females in China with an attempt to reference the peak bone
      mineral density (BMD) with the corresponding BTM valley. METHODS: This study
      included 546 premenopausal and 394 postmenopausal women. The levels of several
      BTMs were determined, and the BMD was measured using a dual-energy X-ray
      absorptiometry. RESULTS: The BTMs of postmenopausal women were 17-96 % higher
      than premenopausal women. The change of BTM with age presented an optimal
      goodness-of-fit according to the cubic regression model (R (2) = 0.074-0.346, all
      P = 0.000). All kinds of BTM levels were positively correlated with age in
      premenopausal women aged 27-56 years old (r = 0.167-0.502, P = 0.023-0.000).
      Except for uCTX, the BTM reference value determined using a curve-fitting valley
      was significantly lower than the reference values for premenopausal women. The
      BTM reference values determined in this study were also significantly different
      from the reference values given by the manufacturers of the reagents used.
      CONCLUSIONS: This study found that the changes of level with age of BTMs in
      Chinese women present an optimal goodness-of-fit according to the cubic
      regression model. The fitting valley corresponds to the BMD fitting peak and may
      possibly be an effective means of determining the BTM reference intervals.

PMID- 23877869
TI  - Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in
      an orthotopic pancreatic cancer xenograft.
AB  - PURPOSE: Adenocarcinoma of the pancreas remains one of the most lethal human
      cancers. The high mortality rates associated with this form of cancer are
      subsequent to late-stage clinical presentation and diagnosis, when surgery is
      rarely possible and of modest chemotherapeutic impact. Survival rates following
      diagnosis with advanced pancreatic cancer are very low; typical mortality rates
      of 50% are expected within 3 months of diagnosis. However, adjuvant chemotherapy
      improves the prognosis of patients even after palliative surgery, and successful
      newer neoadjuvant chemotherapeutical modalities have recently been reported. For
      patients whose tumours appear unresectable, chemotherapy remains the only option.
      During the past two decades, the nucleoside analogue gemcitabine has become the
      first-line chemotherapy for pancreatic adenocarcinoma. In this study, we aim to
      increase the delivery of gemcitabine to pancreatic tumours by exploring the
      effect of sonoporation for localised drug delivery of gemcitabine in an
      orthotopic xenograft mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: An
      orthotopic xenograft mouse model of luciferase expressing MIA PaCa-2 cells was
      developed, exhibiting disease development similar to human pancreatic
      adenocarcinoma. Subsequently, two groups of mice were treated with gemcitabine
      alone and gemcitabine combined with sonoporation; saline-treated mice were used
      as a control group. A custom-made focused ultrasound transducer using clinically
      safe acoustic conditions in combination with SonoVue(r) ultrasound contrast agent
      was used to induce sonoporation in the localised region of the primary tumour
      only. Whole-body disease development was measured using bioluminescence imaging,
      and primary tumour development was measured using 3D ultrasound. RESULTS:
      Following just two treatments combining sonoporation and gemcitabine, primary
      tumour volumes were significantly lower than control groups. Additional therapy
      dramatically inhibited primary tumour growth throughout the course of the
      disease, with median survival increases of up to 10% demonstrated in comparison
      to the control groups. CONCLUSION: Combined sonoporation and gemcitabine therapy
      significantly impedes primary tumour development in an orthotopic xenograft model
      of human pancreatic cancer, suggesting additional clinical benefits for patients
      treated with gemcitabine in combination with sonoporation.

PMID- 23877871
TI  - Time dependency of bone density estimation from computed tomography with
      intravenous contrast agent administration.
AB  - Our study has demonstrated that in contrast-enhanced multi-detector computed
      tomography (MDCT)-based bone density measurements, the scan delay time after
      contrast agent administration is a statistically significant variable for the
      derivation of quantitative computed tomography (QCT)-equivalent bone mineral
      density (BMD) values. INTRODUCTION: Earlier investigators have proposed to derive
      QCT-equivalent BMD values from contrast-enhanced MDCT scans by using a merely
      density-based conversion equation. The purpose of this study was to investigate
      whether the scan delay after intravenous (IV) contrast agent administration might
      affect BMD values derived in this way. METHODS: A retrospective data analysis was
      performed on 198 subjects who underwent standardized biphasic MDCT. Average
      densities values (in Hounsfield units) of lumbar vertebral bodies 1 to 3 (L1-L3)
      were compared between phases I and II of the biphasic MDCT scan. Furthermore, QCT
      equivalent BMD (BMDQCT) values were calculated using a previously published
      conversion equation. RESULTS: Paired t-test analysis revealed that IV contrast
      agent administration leads to a statistically significant increase (8.6 %; p <
      0.0001) in overall density of L1-L3 from phases I to II. Moreover, comparison of
      BMDQCT values between phases I and II reveals a change from osteoporotic to
      osteopenic in 4.5 % of the study population and from osteopenic to normal for
      11.1 % of the subjects. Furthermore, it was revealed that the density increase
      from phases I to II shows a weak, yet statistically significant (p < 0.001) age
      dependency. CONCLUSIONS: Our study demonstrates that the use of a mere density
      based conversion equation for deriving BMDQCT from MDCT scans ignores time
      dependency as an important variable. Furthermore, our results indicate that the
      actual age-dependent BMD itself might be another relevant variable that needs to
      be included in a MDCT-to-QCT conversion equation.

PMID- 23877872
TI  - Comparison of two different adjuvant treatment modalities for pN3 gastric cancer
      patients after D2 lymph node dissection: can we avoid radiotherapy in a subgroup
      of patients?
AB  - Adjuvant chemoradiotherapy (CRT) is the standard of care for gastric cancer
      patients in the USA. However, in countries where D2 lymph node dissection is
      performed, the effect of radiotherapy on locoregional recurrence is
      controversial. The aim of this study is to compare the outcomes in pN3 gastric
      cancer patients following two adjuvant treatment modalities: chemotherapy (CT)
      and CRT after D2 lymph node dissection. Between 2005 and 2009, 71 gastric cancer
      patients who underwent D2 lymph node dissection and had pTanyN3M0 stage
      (according to AJCC 6th edition) were identified. Fifty-three patients were
      treated with CT and 18 patients received CRT. CRT consisted of bolus fluorouracil
      (FU) 425 mg/m(2) and leucovorin 20 mg/m(2) before, after, and during
      radiotherapy. For the CT arm, treatment protocols consisted of combination
      therapies involving FU and cisplatin as the backbone. Median overall survival
      (OS) and disease-free survival (DFS) rates for all patients were 26.3 months (15
      37.7 months) and 12.5 months (8-17.1 months). Median OS in CT arm was 26.8 months
      and it was 34.2 months for CRT arm (p = 0.74). DFS rates did not differ
      statistically either (p = 0.56, 12.5 and 15.2 months for CT and CRT,
      respectively). Locoregional recurrence rates were also similar (p = 0.63). Only
      metastatic/dissected lymph node ratio (>=0.75) was identified as a prognostic
      factor in both univariate and multivariate analyses for DFS. Comparison of CT
      versus CRT for N3 stage gastric cancer patients with D2 lymph node dissection did
      not reveal any statistically significant difference in survival rates and
      locoregional recurrence.

PMID- 23877873
TI  - The basic helix-loop-helix (bHLH) proteins in breast cancer progression.

PMID- 23877874
TI  - 'Focus on feet'--the effects of systemic lupus erythematosus: a narrative review
      of the literature.
AB  - BACKGROUND: The manifestations of systemic lupus erythematosus (SLE) vary between
      individuals, from the severe and life-threatening renal and central nervous
      system involvement, to the involvement of skin, musculoskeletal and vascular
      system, and the complications of infection influencing the quality of life.
      However, as specific manifestations affecting the lower limb are perceived as
      receiving little focus, the purpose of this narrative literature review is to
      identify the specific factors associated with SLE that may have implications for
      lower limb and foot morbidity. METHOD: A structured search of databases was
      conducted. The inclusion was restricted to publications in the English language,
      those that specifically investigate the feet as affected with SLE. No restriction
      on year of publication was imposed to reduce publication bias and to capture as
      many publication in relation to feet. RESULTS: Eleven papers fulfilled the
      inclusion criteria. There were seven additional papers that made observations
      related to the articular or vascular complications of the feet. This narrative
      review provides some information on how SLE affects the lower limb and foot in
      relation to the musculoskeletal and vascular systems. However, there is a lack of
      literature that specifically focuses on all the manifestations of SLE and the
      complications associated with its management. DISCUSSION: There are indications
      that SLE affects lower limb and foot morbidity but the scale of these problems is
      unclear and this is partly because of the absence of research and the lack of a
      'gold standard' framework for the assessment of the lower limb and foot. In
      addition to clinical foot health assessment, ultrasonography may be a useful
      alternative to plain film radiography or magnetic resonance imaging (MRI) in
      capturing the extent of articular and extra-articular manifestations. Further,
      the Ankle Brachial Pressure Index (ABPI) may be useful in identifying those with
      atherosclerosis and ischaemia. CONCLUSION: There are indications that SLE affects
      lower limb and foot morbidity but the scale of these problems and effective
      management of them is unclear. Therefore, further research is warranted in order
      to better understand the impact of SLE on the foot and lower limb and its impact
      on quality of life.

PMID- 23877875
TI  - A superior catalyst with dual redox cycles for the selective reduction of NO(x)
      by ammonia.
AB  - An environmentally benign Cu-Ce-Ti oxide catalyst exhibited excellent NH3-SCR
      activity, high N2 selectivity and strong resistance against H2O and SO2 with a
      broad operation temperature window. The dual redox cycles (Cu(2+) + Ce(3+) <->
      Cu(+) + Ce(4+), Cu(2+) + Ti(3+) <-> Cu(+) + Ti(4+)) play key roles for the
      superior catalytic deNOx performance.

PMID- 23877876
TI  - Cutaneous involvement by post-polycythemia vera myelofibrosis.

PMID- 23877877
TI  - Sorghum extracellular leucine-rich repeat protein SbLRR2 mediates lead tolerance
      in transgenic Arabidopsis.
AB  - A sorghum pathogen-inducible gene predicted to encode a simple extracellular
      leucine-rich repeat (LRR) protein SbLRR2 was previously isolated. LRR was the
      only domain identified in SbLRR2 and its homologous sequences. Phylogenetic
      analysis revealed that they are distinct from the simple extracellular LRR
      proteins reported previously. Agrobacterium-mediated transient expression in
      tobacco leaf cells demonstrated that the SbLRR2-EYFP (enhanced yellow fluorescent
      protein) fusion protein was targeted to the extracellular space. Transgenic
      analysis of SbLRR2 revealed its role in enhancing lead [Pb(II)] tolerance in
      Arabidopsis. Consequently, SbLRR2-overexpressing lines were found to show
      alleviated Pb(II)-induced root inhibition, lower levels of Pb(II) accumulation
      and enhanced transcription of AtPDR12 which encodes a plasma membrane ATP-bind
      cassette (ABC)-type transporter formerly shown to contribute to Pb(II)
      detoxification. However, all the Pb(II) tolerance responses were abolished when
      SbLRR2 was overexpressed in an atpdr12 T-DNA insertion line. The extracellular
      localization of SbLRR2 was also shown to be essential for the Pb(II) phenotypes
      and AtPDR12 up-regulation. Taken together, SbLRR2 appears to mediate Pb(II)
      tolerance through the elevation of AtPDR12 expression in transgenic Arabidopsis,
      thus activating a glutathione-independent mechanism for detoxification. Further
      investigations revealed the Pb(II)-induced transcriptional activation of SbLRR2
      and several highly conserved AtPDR12 homologs in sorghum seedlings, suggesting
      the possibility of a common molecular mechanism for Pb(II) tolerance in diverse
      plant species.

PMID- 23877878
TI  - [Improvement of power and illumination source of the indirect binocular
      ophthalmoscope designed by Foerster].
AB  - BACKGROUND: Since 1982, the indirect binocular ophthalmoscope designed by
      Foerster has been in use in ophthalmology. The option to implement a new
      illumination technique using a light-emitting diode (LED) and a new power source
      should be evaluated in terms of technical feasibility and patient safety.
      METHODS: The cooling element was redesigned to accommodate the new LED
      electronics and their components, including an option for a variable brightness
      control. A more compact rechargeable battery was utilized with variable fixation
      at the headband or elsewhere. Photometric measurements of light intensity and the
      operating time were planned. Furthermore, a review of the new lighting technology
      in terms of EN ISO 15004-2 and EN ISO 10943 was necessary. RESULTS: Technical
      adjustments to accommodate the LED inside the cooling element could be realised.
      The power source was a modern rechargeable lithium-ion battery with variable
      fixation. The luminous intensity of the LED is superior to that of the halogen
      lamp and the operating time was increased to 520 minutes. The required limits
      according to DIN EN ISO 15004-2 for ophthalmic devices were met by our
      measurements. CONCLUSION: The optimisation of the indirect binocular
      ophthalmoscope brings improvements in illumination intensity and operating time.
      A conversion for models already in use is possible. A certified appraisal for
      compliance with the appropriate standards is the next step.

PMID- 23877879
TI  - Recent advances in synthesis, characterization of hydroxyapatite/polyurethane
      composites and study of their biocompatible properties.
AB  - The development of engineered biomaterials that mimic bone tissues is a promising
      research area that benefits from a growing interest. Polymers and polymer-ceramic
      composites are the principle materials investigated for the development of
      synthetic bone scaffolds thanks to their proven biocompatibility and
      biostability. Several polymers have been combined with calcium phosphates (mainly
      hydroxyapatite) to prepare nanocomposites with improved biocompatible and
      mechanical properties. Here, we report the hydrothermal synthesis in high
      pressure conditions of nanostructured composites based on hydroxyapatite and
      polyurethane functionalized with carboxyl and thiol groups. Cell-material
      interactions were investigated for potential applications of these new types of
      composites as coating for orthopedic implants. Physical-chemical and
      morphological characteristics of hydroxyapatite/polyurethane composites were
      evaluated for different compositions, showing their dependence on synthesis
      parameters (pressure, temperature). In vitro experiments, performed to verify if
      these composites are biocompatible cell culture substrates, showed that they are
      not toxic and do not affect cell viability. 

PMID- 23877880
TI  - Vascular complications of fungal meningitis attributed to injections of
      contaminated methylprednisolone acetate.
AB  - IMPORTANCE: Fungal meningitis due to injections of contaminated
      methylprednisolone acetate can present with vascular sequelae in immunocompetent
      individuals. This is particularly germane to neurologists because better
      recognition of the clinical characteristics of patients with fungal meningitis
      and ischemic stroke will provide more timely and efficient care. OBSERVATIONS: In
      a case series, 3 patients presented to Vanderbilt University Medical Center in
      Nashville, Tennessee, with acute ischemic stroke and later received a diagnosis
      of fungal meningitis attributed to epidural injections of contaminated
      methylprednisolone. Of these 3 patients, 2 were women, and the mean age for all 3
      was 75.3 years. Their medical records and imaging scans were reviewed. All 3
      patients presented with acute ischemic strokes and had a history of epidural
      spinal injections of methylprednisolone for low back pain. All 3 patients had 1
      or more traditional risk factors for stroke. There were differing vascular
      patterns of presentation: 2 patients presented with small-vessel (lacunar)
      infarctions, whereas 1 patient presented with a large-vessel infarct. Of these 3
      patients, 2 died and underwent an autopsy, which revealed Exserohilum rostratum
      as the presumed cause of death. For 2 cases, fever and meningeal signs were
      absent at presentation. CONCLUSIONS AND RELEVANCE: Patients with fungal
      meningitis may present with ischemic stroke detected on initial imaging scans. A
      definitive diagnosis should not delay early antifungal treatment.

PMID- 23877881
TI  - Our new venture into Eco-Paediatrics.

PMID- 23877882
TI  - Systematic reviews of bruising in relation to child abuse-what have we learnt: an
      overview of review updates.
AB  - BACKGROUND: Dogma has long prevailed regarding the ageing of bruises, and whether
      certain patterns of bruising are suggestive or diagnostic of child abuse.
      OBJECTIVES: We conducted the first Systematic Reviews addressing these two
      issues, to determine the scientific basis for current clinical practice. There
      have been seven updates since 2004. METHODS: An all language literature search
      was performed across 13 databases, 1951-2004, using >60 key words, supplemented
      by 'snowballing' techniques. Quality standards included a novel confirmation of
      abuse scale. Updates used expanded key words, and a higher standard for
      confirmation of abuse. RESULTS: Of 1495 potential studies, only three met the
      inclusion criteria for ageing of bruises in 2004, confirming that it is
      inaccurate to do so with the naked eye. This was roundly rejected when first
      reported, generating a wave of new studies attempting to determine a
      scientifically valid method to age bruises, none of which are applicable in
      children yet. Regarding patterns of bruising that may be suggestive or diagnostic
      of abuse, we included 23 of 167 studies reviewed in 2004, although only 2 were
      comparative studies. Included studies noted that unintentional bruises occur
      predominantly on the front of the body, over bony prominences and their presence
      is directly correlated to the child's level of independent mobility. Bruising
      patterns in abused children, differed in location (most common site being face,
      neck, ear, head, trunk, buttocks, arms), and tended to be larger. Updates have
      included a further 14 studies, including bruising in disabled children, defining
      distinguishing patterns in severely injured abused and non-abused children, and
      importance of petechiae. CONCLUSIONS: Systematic Reviews of bruising challenged
      accepted wisdom regarding ageing of bruises, which had no scientific basis;
      stimulated higher quality research on patterns of bruises distinguishing abusive
      and non-abusive bruising patterns, and highlighted the benefits of regular
      updates of these reviews.

PMID- 23877883
TI  - Antihistamines or decongestants for otitis media with effusion-do they work?:
      ...reducing waste in child health one intervention at a time.
AB  - Eco-paediatrics is an occasional feature in Evidence-Based Child Health: A
      Cochrane Review Journal. Our goal is to contribute to the worldwide discussion on
      reducing waste in health care. In each instalment, we will select a recent
      Cochrane review highlighting a practice, still in use, which the available
      evidence tells us should be discontinued. 

PMID- 23877884
TI  - Cochrane review: social skills groups for people aged 6 to 21 with autism
      spectrum disorders (ASD).
AB  - BACKGROUND: Since autism was first described, major difficulties in social
      interaction have been a defining feature of individuals with autism spectrum
      disorders (ASD). Social skills groups are a common intervention for individuals
      with ASD. Although a frequently recommended practice, the few studies that have
      addressed the efficacy of social skills groups have shown mixed results.
      OBJECTIVES: To determine the effectiveness of social skills groups for improving
      social competence, social communication, and quality of life for people with ASD
      who are six to 21 years of age. SEARCH METHODS: We searched the following
      databases in December 2011: CENTRAL (2011 Issue 4), MEDLINE (1948 to November
      Week 3, 2011), EMBASE (1980 to Week 50, 2011), PsycINFO (1887 to December Week 2,
      2011), CINAHL (1937 to current), ERIC (1966 to current), Sociological Abstracts
      (1952 to current), OCLC WorldCat (12 December 2011), Social Science Citation
      Index (1970 to 16 December 2011), and the metaRegister of Controlled Trials (20
      December 2011). We also searched the reference lists of published papers.
      SELECTION CRITERIA: Randomized control trials (RCTs) comparing treatment (social
      skills groups) with a control group who were not receiving the treatment for
      participants aged six to 21 years with ASD. The control group could be no
      intervention, wait list, or treatment as usual. Outcomes sought were standardized
      measures of social competence, social communication, quality of life, emotion
      recognition, and any other specific behaviors. DATA COLLECTION AND ANALYSIS: Two
      review authors independently selected and appraised studies for inclusion and
      assessed the risk of bias in each included study. All outcome data were
      continuous and standardized mean difference effect sizes (ES) with small sample
      correction were calculated. We conducted random-effects meta-analysis where
      possible. MAIN RESULTS: We included five RCTs evaluating the effects of social
      skills groups in 196 participants with ASD aged 6 to 21 years old. The results
      show there is some evidence that social skills groups improve overall social
      competence (ES = 0.47, 95% confidence interval (CI) 0.16 to 0.78, P = 0.003) and
      friendship quality (ES = 0.41, 95% CI 0.02 to 0.81, P = 0.04) for this
      population. No differences were found between treatment and control groups in
      relation to emotional recognition (ES = 0.34, 95% CI -0.20 to 0.88, P = 0.21)
      assessed in two studies or social communication as related to the understanding
      of idioms (ES = 0.05, 95% CI -0.63 to 0.72, P = 0.89), which was assessed in only
      one study. Two additional quality of life outcomes were evaluated, with results
      of single studies suggesting decreases in loneliness (ES = -0.66, 95% CI -1.15 to
      -0.17) but no effect on child or parental depression. No adverse events were
      reported. Given the nature of the intervention and the selected outcome measures,
      the risk of performance and detection bias are high. There is limited
      generalizability from the studies as they were all conducted in the US; they
      focused mainly on children aged 7 to 12, and the participants were all of average
      or above average intelligence. AUTHORS' CONCLUSIONS: There is some evidence that
      social skills groups can improve social competence for some children and
      adolescents with ASD. More research is needed to draw more robust conclusions,
      especially with respect to improvements in quality of life.

PMID- 23877885
TI  - Commentary on 'Social skills groups for people aged 6 to 21 with autism spectrum
      disorders (ASD)'.
AB  - This is a commentary on a Cochrane review, published in this issue of EBCH, first
      published as: Reichow B, Steiner AM, Volkmar F. Social skills groups for people
      aged 6 to 21 with autism spectrum disorders (ASD). Cochrane Database of
      Systematic Reviews 2012, Issue 7. Art. No.: CD008511. DOI:
      10.1002/14651858.CD008511.pub2. Further information for this Cochrane review is
      available in this issue of EBCH in the accompanying Summary article. 

PMID- 23877886
TI  - Cochrane review: behavioural and cognitive-behavioural group-based parenting
      programmes for early-onset conduct problems in children aged 3 to 12 years
      (Review).
AB  - BACKGROUND: Early-onset child conduct problems are common and costly. A large
      number of studies and some previous reviews have focused on behavioural and
      cognitive-behavioural group-based parenting interventions, but methodological
      limitations are commonplace and evidence for the effectiveness and cost
      effectiveness of these programmes has been unclear. OBJECTIVES: To assess the
      effectiveness and cost-effectiveness of behavioural and cognitive-behavioural
      group-based parenting programmes for improving child conduct problems, parental
      mental health and parenting skills. SEARCH METHODS: We searched the following
      databases between 23 and 31 January 2011: CENTRAL (2011, Issue 1), MEDLINE (1950
      to current), EMBASE (1980 to current), CINAHL (1982 to current), PsycINFO (1872
      to current), Social Science Citation Index (1956 to current), ASSIA (1987 to
      current), ERIC (1966 to current), Sociological Abstracts (1963 to current),
      Academic Search Premier (1970 to current), Econlit (1969 to current), PEDE (1980
      to current), Dissertations and Theses Abstracts (1980 to present), NHS EED
      (searched 31 January 2011), HEED (searched 31 January 2011), DARE (searched 31
      January 2011), HTA (searched 31 January 2011), mRCT (searched 29 January 2011).
      We searched the following parent training websites on 31 January 2011: Triple P
      Library, Incredible Years Library and Parent Management Training. We also
      searched the reference lists of studies and reviews. SELECTION CRITERIA: We
      included studies if: (1) they involved randomised controlled trials (RCTs) or
      quasi-randomised controlled trials of behavioural and cognitive-behavioural group
      based parenting interventions for parents of children aged 3 to 12 years with
      conduct problems, and (2) incorporated an intervention group versus a waiting
      list, no treatment or standard treatment control group. We only included studies
      that used at least one standardised instrument to measure child conduct problems.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias
      in the trials and the methodological quality of health economic studies. Two
      authors also independently extracted data. We contacted study authors for
      additional information. MAIN RESULTS: This review includes 13 trials (10 RCTs and
      three quasi-randomised trials), as well as two economic evaluations based on two
      of the trials. Overall, there were 1078 participants (646 in the intervention
      group; 432 in the control group). The results indicate that parent training
      produced a statistically significant reduction in child conduct problems, whether
      assessed by parents (standardised mean difference (SMD) -0.53; 95% confidence
      interval (CI) -0.72 to -0.34) or independently assessed (SMD -0.44; 95% CI -0.77
      to -0.11). The intervention led to statistically significant improvements in
      parental mental health (SMD -0.36; 95% CI -0.52 to -0.20) and positive parenting
      skills, based on both parent reports (SMD -0.53; 95% CI -0.90 to -0.16) and
      independent reports (SMD -0.47; 95% CI -0.65 to -0.29). Parent training also
      produced a statistically significant reduction in negative or harsh parenting
      practices according to both parent reports (SMD -0.77; 95% CI -0.96 to -0.59) and
      independent assessments (SMD -0.42; 95% CI -0.67 to -0.16). Moreover, the
      intervention demonstrated evidence of cost-effectiveness. When compared to a
      waiting list control group, there was a cost of approximately $2500 (GBP 1712;
      EUR 2217) per family to bring the average child with clinical levels of conduct
      problems into the non-clinical range. These costs of programme delivery are
      modest when compared with the long-term health, social, educational and legal
      costs associated with childhood conduct problems. AUTHORS' CONCLUSIONS:
      Behavioural and cognitive-behavioural group-based parenting interventions are
      effective and cost-effective for improving child conduct problems, parental
      mental health and parenting skills in the short term. The cost of programme
      delivery was modest when compared with the long-term health, social, educational
      and legal costs associated with childhood conduct problems. Further research is
      needed on the long-term assessment of outcomes.

PMID- 23877887
TI  - Commentary on 'Behavioural and cognitive-behavioural group-based parenting
      programmes for early-onset conduct problems in children aged 3 to 12 years'.
AB  - This is a commentary on a Cochrane review, published in this issue of EBCH, first
      published as: Furlong M, McGilloway S, Bywater T, Hutchings J, Smith SM, Donnelly
      M. Behavioural and cognitive-behavioural group-based parenting programmes for
      early-onset conduct problems in children aged 3 to 12 years. Cochrane Database of
      Systematic Reviews 2012, Issue 2. Art. No.: CD008225. DoI:
      10.1002/14651858.CD008225.pub2. 

PMID- 23877888
TI  - Commentary on 'Interventions for restoring patency of central venous catheter
      lumens'.
AB  - This is a commentary on a Cochrane review, published in this issue of EBCH, first
      published as: van Miert C, Hill R, Jones L. Interventions for restoring patency
      of occluded central venous catheter lumens. Cochrane Database of Systematic
      Reviews 2012, Issue 4. Art. No.: CD007119. DoI: 10.1002/14651858.CD007119.pub2.
      Further information for this Cochrane review is available in this issue of EBCH
      in the accompanying Summary article. 

PMID- 23877889
TI  - Poly([1,4]Dithiino[2,3-c]Furan): the synthesis, electrochemistry, and
      optoelectronic properties of a furan-containing polymer.
AB  - The chemical synthesis of a novel polyfuran, poly(2,3-bis(hexylthio)
      [1,4]dithiino[2,3-c]furan) (PBDF), substituted at the 2,3-positions with an S
      alkylated dithiin unit, is reported. The new polymer has been characterized in
      terms of its electronic absorption, electrochemical, and thermal properties.
      Employment of the dithiin moiety provides intrinsic additional electroactivity,
      as well as a functional handle for substitution with alkyl groups, enhancing the
      processability of the polymer. The new polymer is compared with the closely
      related and well-established literature compounds PEDOT and PEDTT as well
      studied, highly chalcogenated polythiophenes. 

PMID- 23877890
TI  - Regeneration-on-a-chip? The perspectives on use of microfluidics in regenerative
      medicine.
AB  - The aim of regenerative medicine is to restore or establish normal function of
      damaged tissues or organs. Tremendous efforts are placed into development of
      novel regenerative strategies, involving (stem) cells, soluble factors,
      biomaterials or combinations thereof, as a result of the growing need caused by
      continuous population aging. To satisfy this need, fast and reliable assessment
      of (biological) performance is sought, not only to select the potentially
      interesting candidates, but also to rule out poor ones at an early stage of
      development. Microfluidics may provide a new avenue to accelerate research and
      development in the field of regenerative medicine as it has proven its maturity
      for the realization of high-throughput screening platforms. In addition,
      microfluidic systems offer other advantages such as the possibility to create in
      vivo-like microenvironments. Besides the complexity of organs or tissues that
      need to be regenerated, regenerative medicine brings additional challenges of
      complex regeneration processes and strategies. The question therefore arises
      whether so much complexity can be integrated into microfluidic systems without
      compromising reliability and throughput of assays. With this review, we aim to
      investigate whether microfluidics can become widely applied in regenerative
      medicine research and/or strategies. 

PMID- 23877891
TI  - Analysis of supraglottic activity during vocalization in healthy singers.
AB  - OBJECTIVES/HYPOTHESIS: The present study aims to evaluate the degree of anterior
      posterior and medial supraglottic laryngeal compression in healthy singers of
      different voice classifications while singing different pitches, loudness, and
      phonatory tasks. STUDY DESIGN: Prospective study. METHODS: Thirty-six classically
      trained singers (11 sopranos, 11 mezzo-sopranos, six tenors, and eight baritones)
      with at least 5 years of voice training and absence of any voice pathology within
      the past year were included. Flexible endoscopic voice evaluations were recorded
      and edited to include samples of different pitches, levels of loudness, and
      phonatory tasks. Sound was removed from the video samples. Two blinded
      laryngologists were asked to assess medial and anterior-posterior supraglottic
      compression using a visual analog scale for each sample. RESULTS: Medial
      compression was significantly greater in male subjects and specifically tenors
      during loud phonation, during high pitch, and while phonating the vowel /a/.
      Anterior-posterior compression was also significantly greater in males and
      specifically baritones during loud voice production and with phonation of the
      vowel /a/. No difference was noted in relation to pitch. Correlation between
      anterior-posterior and medial compression was demonstrated. Medial compression
      was less severe than anterior-posterior compression. CONCLUSIONS: Supraglottic
      hyperfunction is present in healthy singers. Recognizing factors that might
      affect supraglottic hyperfunction in the healthy voice may help us to understand
      when hyperfunction is truly contributing to a patient's vocal pathology. LEVEL OF
      EVIDENCE: 4.

PMID- 23877892
TI  - Pseudozyma vetiver sp. nov., a novel anamorphic ustilaginomycetous yeast species
      isolated from the phylloplane in Thailand.
AB  - Three strains representing one novel yeast species were isolated from the
      phylloplanes of the vetiver grasses (DMKU-LV90 and DMKU-LV99(T)) and sugarcane
      (DMKU-SP260) collected in Thailand by leaf washing followed by a plating
      technique. On the basis of morphological, biochemical, physiological and
      chemotaxonomic characteristics and the sequence analysis of the D1/D2 region of
      the large subunit (LSU) rRNA gene and the internal transcribed spacer region
      (ITS), the three strains were found to represent a single novel anamorphic
      ustilaginomycetous yeast species in the genus Pseudozyma. The name Pseudozyma
      vetiver sp. nov. is proposed for this novel species. The type strain is DMKU
      LV99(T) (BCC 61021 = CBS 12824). The novel species showed phylogenetic
      relationships to the other members of the genus Pseudozyma and to teleomorphic
      fungal genera, namely Ustilago, Sporisorium and Anomalomyces in Ustilaginaceae,
      Ustilaginales. The three strains showed identical sequences both in the D1/D2 and
      ITS regions. The Pseudozyma species closest to the novel species in terms of
      pairwise sequence similarity in the D1/D2 region was Pseudozyma pruni but with
      2.3 % nucleotide substitutions (14 nucleotide substitutions and no gaps out of
      606 nt). The novel species and P. pruni differed by 10.9 % nucleotide
      substitutions (75 nucleotide substitutions and 31 gaps out of 691 nt) in the ITS
      region. The phylogenetic analysis based on the combined sequences of the ITS
      region and the D1/D2 region of the LSU rRNA gene showed that the novel species
      was found to be most closely related to Pseudozyma fusiformata but with 2.9 %
      nucleotide substitutions in the D1/D2 region and 7.4 % nucleotide substitutions
      in the ITS region. 

PMID- 23877893
TI  - Halomonas zhaodongensis sp. nov., a slightly halophilic bacterium isolated from
      saline-alkaline soils in Zhaodong, China.
AB  - A slightly halophilic bacterium (strain NEAU-ST10-25(T)) was isolated from saline
      alkaline soils in Zhaodong City, Heilongjiang Province, China. The strain is a
      Gram-negative, aerobic motile rod. It accumulates poly-beta-hydroxyalkanoate and
      produces exopolysaccharide. It produces beige-yellow colonies. Growth occurs at
      NaCl concentrations (w/v) of 0-15 % (optimum 3 %), at temperatures of 4-60 
      degrees C (optimum 35  degrees C) and at pH 6-12 (optimum pH 9). Its G+C content
      is 53.8 mol%. Phylogenetic analyses based on the separate 16S rRNA gene and
      concatenation of the 16S rRNA, gyrB and rpoD genes indicate that it belongs to
      the genus Halomonas in the class Gammaproteobacteria. The most phylogenetically
      related species is Halomonas alkaliphila DSM 16354(T), with which strain NEAU
      ST10-25(T) showed 16S rRNA, gyrB and rpoD gene sequence similarities of 99.2,
      82.3 and 88.2 %, respectively. The results of DNA-DNA hybridization assays showed
      60.47 +/- 0.69 % DNA relatedness between strain NEAU-ST10-25(T) and H.
      alkaliphila DSM 16354(T), 42.43 +/- 0.37 % between strain NEAU-ST10-25(T) and
      Halomonas venusta DSM 4743(T) and 30.62 +/- 0.43 % between strain NEAU-ST10-25(T)
      and Halomonas hydrothermalis DSM 15725(T). The major fatty acids are C18:1
      omega7c (62.3 %), C16:0 (17.6 %), C16:1 omega7c/C16:1 omega6c (7.7 %), C14:0 (2.9
      %), C12:0 3-OH (2.8 %), C10:0 (2.1 %) and C18:1 omega9c (1.6 %) and the
      predominant respiratory quinone is ubiquinone 9 (Q-9). The proposed name is
      Halomonas zhaodongensis, NEAU-ST10-25(T) (=CGMCC 1.12286(T) = DSM 25869(T)) being
      the type strain. 

PMID- 23877895
TI  - Guidelines for general anaesthesia in the elderly of the Committee on Quality and
      Safety in Anaesthesia, Polish Society of Anaesthesiology and Intensive Therapy.

PMID- 23877894
TI  - Protection of mice against lethal rabies virus challenge using short interfering
      RNAs (siRNAs) delivered through lentiviral vector.
AB  - The antiviral potential of small interfering RNAs (siRNAs) targeting rabies virus
      (RV) polymerase (L) and nucleoprotein (N) genes delivered through lentiviral
      vector was investigated. For in vitro evaluation, siRNAs expressing BHK-21 cell
      lines (BHK-L and BHK-N) were developed using transduction with Lenti-L and Lenti
      N lentiviruses encoding siRNAs against RV-L and N genes, respectively. When these
      cell lines were challenged in vitro with RV Pasteur virus-11 (PV-11) strain,
      there was reduction in number of RV-specific foci and target gene transcripts
      indicating inhibitory effect on RV multiplication. For in vivo evaluation, mice
      were treated intracerebrally with lentiviruses and challenged with 20 LD50 of RV
      challenge virus standard-11 (CVS-11) strain by intramuscular route in masseter
      muscle. Five out of eight mice treated with Lenti-N survived indicating 62.5 %
      protection. The control and Lenti-L-treated mice died within 7-10 days indicating
      lethal nature of challenge virus and no protection. These results demonstrated
      that siRNA targeting RV-N could not only inhibit RV multiplication, but also
      conferred protection in mice against lethal RV challenge. These findings have
      implication on therapeutic use of siRNA targeting RV-N against RV infection.

PMID- 23877896
TI  - Health-care associated infection in the newly-opened intensive care unit.
AB  - BACKGROUND: Health-care associated infections (HAI) are common complications in
      ICU patients as an effect of high invasive device utilization rate. The aim of
      the study was to analyze the epidemiology of ventilator - associated pneumonia
      (VAP), blood stream infections (BSI), urinary tract infections (UTI) and surgical
      site infections (SSI) in newly opened medical-surgical intensive care unit.
      METHODS: VAP, BSI, UTI and SSI were detected and registered by hospital Infection
      Control Team according to CDC criteria during first 12 months following opening
      of new ICU. RESULTS: During 12-month period HAI was diagnosed in 44 out of 168
      patients (26%). The ventilator utilization rate was 72%. The incidence density of
      VAP was 15.5/1000 ventilator days. The central line utilization was 100%. The BSI
      rate was 5/1000 catheter days. The urinary catheter utilization was 95%. The UTI
      rate was 1.9/1000 catheterization days. In 8 out of 60 surgical patients SSI
      occurred (13%). The most common isolates were Gram negative bacteria.
      CONCLUSIONS: The incidence of VAP was higher than the mean values reported for
      USA, western Europe and similar to the mean value reported for developing
      countries. BSI and UTI rate was comparable to those given in NNIS and HELICS
      reports. Effective prevention strategies should be introduced in order to reduce
      high VAP rates

PMID- 23877897
TI  - Comparison of in vitro efficacy of ertapenem, imipenem and meropenem in the
      infections caused by the Enterobacteriaceae strains family.
AB  - BACKGROUND: The members of the bacterial Enterobacteriaceae family play an
      important role in the aetiology of many hospital infections. Some of them are
      able to produce beta-lactamase, an enzyme which induces the resistance of those
      bacteria to penicillins, cephalosporins and, in severe infections, to penicillins
      with beta-lactamase inhibitors. In this situation, the carbapenems become the
      drugs of choice. The objective of this study was to analyse the in vitro efficacy
      of three carbapenems: ertapenem, imipenem and meropenem against bacterial species
      of the Enterobacteriaceae family. METHODS: A total of 99 bacterial species
      (including ten bacterial species producing the ESBL mechanism), isolated between
      September 2011 and March 2012 from diagnostic material collected from patients of
      surgical clinics in the department of motoskeletal system infections and the
      critical care unit, hospitalised in the Military Institute of Medicine in Warsaw,
      were analysed. The values of MIC 50 and MIC 90 were recorded. RESULTS: All
      isolated bacterial species were susceptible to meropenem. One strain of
      Morganella morganii was resistant to imipenem, while one strain of Enterobacter
      cloaceae and one strain of Klebsiella pneumoniae were resistant to ertapenem. In
      the Enterobacteriaceae ESBL(-) group, the values of MIC 50 were 0.006 MUg mL-1
      for ertapenem, 0.19 MUg mL-1 for imipenem, and 0.032 MUg mL-1 for meropenem, and
      the MIC 90 values were: 0.25 MUg mL-1, 0.5 MUg mL-1 and 0.125 MUg mL-1,
      respectively. In the Enterobacteriaceae ESBL(+) group, the values of MIC 50 were
      0.38 MUg mL-1, 0.25 MUg mL-1, 0.064 MUg mL-1, and the values of MIC 90 were 0.5
      MUg mL-1, 0.25 MUg mL-1 and 0.125 MUg mL-1, respectively. CONCLUSIONS: All
      analysed carbapenems had high in vitro efficacy against both Enterobacteriaceae
      ESBL(-) and Enterobacteriaceae ESBL(+) bacterial species.

PMID- 23877898
TI  - Knowledge of newborn resuscitation among emergency medical personnel.
AB  - BACKGROUND: Immediately after birth, approximately 10% of newborns need
      interventions to facilitate lung recruitment and begin spontaneous respiration. A
      full resuscitation procedure is required by < 1% of newborns. Because you can't
      always predict the need to perform CPR, at every birth someone trained to conduct
      such operations should be in attendance. The aim of this study was to investigate
      the understanding of neonatal resuscitation at birth among emergency medical
      personnel. METHODS: This study was conducted in 2012 among a group of 270 people
      (doctors, nurses and paramedics) working in teams of emergency medical services
      in Poland. The study involved the issue of a questionnaire, checking knowledge of
      neonatal resuscitation. Results. 79% of respondents knew the time limits for the
      use of the term 'newborn'. All respondents had knowledge of the order of
      proceedings in CPR (76-100%) and the ratio of compressions to ventilation during
      neonatal resuscitation (76-100%). The group of nurses, compared to doctors and
      paramedics, knew very little about the following topics: energy shock (44% vs.
      100% vs. 100%), tidal volume (24% vs. 92% vs. 78%), and the dose of sodium
      bicarbonate (32% vs. 96% vs. 87%). CONCLUSIONS: The best prepared professional
      groups regarding newborn resuscitation are doctors and paramedics. The incomplete
      knowledge found in nurses should lead to intensified training in this
      occupational group.

PMID- 23877899
TI  - Residual neuromuscular block in elderly patients after surgical procedures under
      general anaesthesia with rocuronium.
AB  - BACKGROUND: Incomplete recovery of neuromuscular function following the
      administration of medium-acting, non- -depolarising agents is one of the most
      feared complications in anaesthesia. We assessed the incidence of postoperative
      residual curarisation (PORC) after general anaesthesia with rocuronium in elderly
      and young patients, and we evaluated possible complications of postoperative
      residual curarisation. METHODS: This observational study included 415 patients
      (ASA physical status I-III) who were undergoing different surgical procedures:
      184 patients were aged >= 65 (range: 65-89) years, and 231 patients were aged 19
      57 years. No patients had renal or hepatic disorders. Patients received
      rocuronium for relaxation. Neuromuscular monitoring was not used
      intraoperatively. Neuromuscular function recovery was spontaneous. Patients were
      transferred to the post-anaesthesia care unit (PACU) after anaesthesia. During
      the first ten minutes in the post-anaesthesia care unit, the presence of
      postoperative residual curarisation was assessed by acceleromyography and train
      of-four (TOF) stimulation. Patient well-being was monitored continuously. During
      hospitalisation, patient medical documentation was assessed for postoperative
      residual curarisation-related complications. RESULTS: TOF ratios were < 0.7 in
      31% of all patients, whereas the block was clinically completely recovered in all
      patients. Postoperative residual curarisation was more frequent in elderly (44%)
      than younger patients (20%) (P < 0.05). Only 73 patients (21 elderly, 52 younger
      patients) had TOF ratios >= 0.9. Hypoxia was more frequent in elderly patients in
      the PACU: 17.9% vs. 8.2% (P < 0.05). Postoperative residual curarisation-related
      pneumonia was observed in one elderly patient. CONCLUSION: Residual paralysis
      remains a major problem in geriatric clinical anaesthesia. Neuromuscular function
      monitoring is obligatory, and pharmacological reversal of relaxation should be
      advised in geriatric patients after using relaxants for general anaesthesia.

PMID- 23877900
TI  - Management of myasthenic crisis in a child.
AB  - Myasthenia gravis is an autoimmune disorder of peripheral nervous system, leading
      to fluctuating muscle weakness. It is caused by circulating antibodies that block
      acetylcholine nicotinic postsynaptic receptors at the postsynaptic neuromuscular
      junction. Myasthenic crisis is a life-threatening complication, which is defined
      as weakness from acquired myasthenia gravis. In this paper we described a 15-year
      old boy who was admitted to the Paediatric Intensive Care Unit due to myasthenic
      crisis. He had suffered not only from myasthenia gravis but also hypothyroidism,
      cerebral palsy and epilepsy. The patient required mechanical ventilation and was
      successfully treated with both plasmapheresis and intravenous immunoglobulins. He
      recovered from the crisis and then thymectomy was performed. Perioperative period
      and anaesthesia passed uncomplicated. Discharged home from the hospital after 2.5
      month-treatment, for the last 4 years, he has only come on scheduled outpatient
      medical appointments. This case reveals that myasthenic crisis, albeit rare, may
      occur in male adolescents. In such cases multidisciplinary care followed by
      surgery becomes a procedure of choice. Concomitant medical problems, if well
      controlled, do not affect the results of outcome of the underlying disease. 

PMID- 23877901
TI  - Anaesthesia in children with osteogenesis imperfecta - report of 14 general
      anaesthetics in three children.
AB  - Osteogenesis imperfecta is a rare, genetically inherited syndrome involving
      connective tissue. It results in extremely fragile bones and disorders of other
      organs and body systems. Children with osteogenesis imperfecta are susceptible to
      bone fractures and often require surgery and anaesthesia. We describe a series of
      14 general anaesthetics in three patients suffering from this disease. In one of
      these cases, perioperative hyperthermia was observed. Anaesthetic management of
      osteogenesis imperfecta and a possible relationship between this syndrome and
      malignant and non-malignant hyperthermia are discussed. 

PMID- 23877902
TI  - Hemothorax as a complication of subclavian vein cannulation with haemodialysis
      catheter - case report.
AB  - We present the case of a 39 year-old male patient admitted to ICU with symptoms
      of acute metabolic acidosis. He was investigated for the presence of methanol and
      glycol. Conservative treatment was initially started, followed by haemodialysis.
      During insertion of a temporary haemodialysis catheter in a location of
      Haapaniemi and Slatis, the patient was conscious but restless; therefore sedation
      was required to continue the procedure. After three hours of haemodialysis, the
      patient's general condition suddenly deteriorated. Hypovolemic shock and acute
      respiratory distress led to hypothesis of right haemothorax, which was rapidly
      confirmed by angio-CT examination. Trachea was intubated, drainage of right
      pleura was performed and aggressive fluid treatment begun. The patient was
      admitted to the operating theatre, and thoracotomy with reconstruction of damaged
      right venous angle was carried out. After the operation, the patient was
      transferred to ICU. He was mechanically ventilated and remained haemodynamically
      unstable. Although fluids and blood-made concentrates were transfused and
      catecholamines continuously administered, his clinical condition deteriorated and
      finally the patient died. We found two independent causes of this fatality:
      hypovolemic shock and acute extrinsic metabolic acidosis. However, this paper
      focuses on the problem of the iatrogenic complication, which was haemothorax. In
      the literature there are described examples of such cases. Authors emphasise the
      most traumatic moment of cannulation as being insertion of the guidewire and
      dilator to perform a tunnel for the catheter. Puncture by needle and localisation
      of the central vein results in fewer complications. Furthermore, we strongly
      recommend monitoring patients after central veins cannulation. All sudden
      deteriorations in clinical condition should be followed by meticulous diagnosis
      for the presence of this life-threatening complication. 

PMID- 23877903
TI  - Systemic effects of epidural steroid injections.
AB  - The aim of this study was to review all the published articles in the English
      language literature regarding the systemic effects of epidural corticosteroid
      injections (ESIs) in humans. ESIs are among the procedures that are most commonly
      used to manage chronic back pain. However, there has been no conclusive review on
      the systemic effects of this popular procedure. Reports were searched for in
      MEDLINE and EMBASE using the terms 'epidural' and 'steroids', 'corticosteroids'
      or 'glucocorticosteroids' up to and including the year 2012. Reports were also
      located by examining the references in the identified articles. We concluded that
      even if epidural steroid injection is one of the most widely- -used techniques to
      treat radicular pain, it must be administered cautiously, with careful monitoring
      for systemic side effects. At the very least, a standardised protocol is
      necessary. 

PMID- 23877904
TI  - Theorethical principles of fluid managment according to physicochemical Stewart
      approach.
AB  - Interpreting acid base disturbances according to the physicochemical Stewart
      approach allows the cause of such abnormalities to be discovered. This method is
      based on three independent variables: SID (strong ion difference), mainly sodium
      and chloride; weak acids concentration - Atot, mainly albumins and phosphate; and
      carbon dioxide tension - pCO2. These three independent variables are responsible
      for the change of water dissociation and for the change in H+ concentration and,
      consequently, the change in serum pH value. The SID value of the fluids
      administered to a patient is responsible for the change of serum SID value and
      therefore causes a change in the patient's acid base status. During the infusion
      of a given fluid, the SID value of the serum becomes closer to the SID value of
      that fluid; on the other hand, the infusion causes a decrease in Atot
      concentration. In order to avoid acid base disturbances connected with fluid
      administration, the SID value of fluids being administered should be greater than
      0 and lower then the serum SID. It has been suggested that fluids should be given
      of which the SID value is as close as possible to the actual serum HCO3
      concentration. Knowing the SID value of the fluid administered, and the serum
      HCO3 concentration, one can expect a change of serum pH after a fluid infusion.
      Administering a fluid with a SID greater than the HCO3 concentration causes a pH
      increase towards alkalosis. Likewise, administering a a fluid with a SID lower
      than the HCO3 concentration causes a pH decrease towards acidosis. It seems that
      knowledge of the electrolyte concentration and the SID value of an administered
      fluid is an important factor regarding acid base disturbances. 

PMID- 23877905
TI  - Sugammadex - indications and clinical use.
AB  - Neuromuscular blocking agents are a substantial element of anaesthesia in almost
      every surgical field. Nevertheless, their use has been associated with rises in
      mortality and morbidity. Of importance are: the general health state of the
      patient, liver and renal function, metabolism and excretion, active metabolites,
      side effects of muscle relaxants and, above all, residual paralysis. Prophylaxis
      of insufficient block reversal consists of neuromuscular transmission monitoring
      using acceleromyography and pharmacologic reversal of blockade. An ideal
      antagonistic agent should be characterised by rapid and complete reversal of
      blockade, disregarding its depth and total dose of muscle relaxant, lack of side
      effects and 100% excretion. These criteria are met by cyclodextrine gamma -
      sugammadex. In contrast to anticholinergic agents, which enhance the
      acetylcholine amount in the postsynaptic part of the neuromuscular junction,
      sugammadex encapsulates myorelaxing agent removing it from the junction.
      Sugammadex binds specifically only muscle relaxants of aminosteroid structure. In
      this paper, we present the current understanding of the characteristics, dosing,
      indications and side effects of sugammadex. 

PMID- 23877906
TI  - Positive end-expiratory pressure during mechanical ventilation and noninvasive
      respiratory support in newborns and children.
AB  - Positive end-expiratory pressure (PEEP) is used during non-invasive and invasive
      ventilation of newborns, infants and children. PEEP improves gas exchange by
      increasing the functional residual capacity, reduces the respiratory effort,
      lowers requirements for respiratory mixture oxygen, and enables to decrease the
      peak inspiratory pressure (PIP) without decreasing the mean airway pressure. Its
      effects on the cardiovascular system appear to be insignificant, particularly in
      patients with severe respiratory failure that is not accompanied by circulatory
      insufficiency. The value of PEEP enabling to provide the optimal conditions for
      improvement of gas exchange should be tailored individually for each patient
      under control of blood gas analysis, PIP and FiO2. This strategy minimises
      ventilator-induced lung injury and prevents the development of circulatory
      failure associated with ventilation. Nasal continuous positive airway pressure
      (NCPAP) used with various PEEP values is a recognised treatment method of
      respiratory failure in newborns, especially in preterm infants. 

PMID- 23877907
TI  - An ounce of prevention....

PMID- 23877908
TI  - Clinical answers: are nonpharmacological interventions for migraine effective in
      children and adolescents?

PMID- 23877909
TI  - Antimicrobials for non-typhoidal Salmonella infection-does it work?: ...reducing
      waste in child health one intervention at a time.
AB  - Eco-paediatrics is an occasional feature in Evidence-Based Child Health: A
      Cochrane Review Journal. Our goal is to contribute to the worldwide discussion on
      reducing waste in health care. In each instalment, we will select a recent
      Cochrane review highlighting a practice, still in use, which the available
      evidence tells us should be discontinued. 

PMID- 23877910
TI  - Home safety education and provision of safety equipment for injury prevention
      (Review).
AB  - BACKGROUND: In industrialised countries injuries (including burns, poisoning or
      drowning) are the leading cause of childhood death and steep social gradients
      exist in child injury mortality and morbidity. The majority of injuries in pre
      school children occur at home but there is little meta-analytic evidence that
      child home safety interventions reduce injury rates or improve a range of safety
      practices, and little evidence on their effect by social group. OBJECTIVES: We
      evaluated the effectiveness of home safety education, with or without the
      provision of low cost, discounted or free equipment (hereafter referred to as
      home safety interventions), in reducing child injury rates or increasing home
      safety practices and whether the effect varied by social group. SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2009,
      Issue 2) in The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid),
      ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of
      Science: Social Sciences Citation Index (SSCI), ISI Web of Science: Conference
      Proceedings Citation Index- Science (CPCI-S), CINAHL (EBSCO) and DARE (2009,
      Issue 2) in The Cochrane Library. We also searched websites and conference
      proceedings and searched the bibliographies of relevant studies and previously
      published reviews. We contacted authors of included studies as well as relevant
      organisations. The most recent search for trials was May 2009. SELECTION
      CRITERIA: Randomised controlled trials (RCTs), non-randomised controlled trials
      and controlled before and after (CBA) studies where home safety education with or
      without the provision of safety equipment was provided to those aged 19 years and
      under, and which reported injury, safety practices or possession of safety
      equipment. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study
      quality and extracted data. We attempted to obtain individual participant level
      data (IPD) for all included studies and summary data and IPD were simultaneously
      combined in meta-regressions by social and demographic variables. Pooled
      incidence rate ratios (IRR) were calculated for injuries which occurred during
      the studies, and pooled odds ratios were calculated for the uptake of safety
      equipment or safety practices, with 95% confidence intervals. MAIN RESULTS:
      Ninety-eight studies, involving 2,605,044 people, are included in this review.
      Fifty-four studies involving 812,705 people were comparable enough to be included
      in at least one meta-analysis. Thirty-five (65%) studies were RCTs. Nineteen
      (35%) of the studies included in the meta-analysis provided IPD. There was a lack
      of evidence that home safety interventions reduced rates of thermal injuries or
      poisoning. There was some evidence that interventions may reduce injury rates
      after adjusting CBA studies for baseline injury rates (IRR 0.89, 95% CI 0.78 to
      1.01). Greater reductions in injury rates were found for interventions delivered
      in the home (IRR 0.75, 95% CI 0.62 to 0.91), and for those interventions not
      providing safety equipment (IRR 0.78, 95% CI 0.66 to 0.92). Home safety
      interventions were effective in increasing the proportion of families with safe
      hot tap water temperatures (OR 1.41, 95% CI 1.07 to 1.86), functional smoke
      alarms (OR 1.81, 95% CI 1.30 to 2.52), a fire escape plan (OR 2.01, 95% CI 1.45
      to 2.77), storing medicines (OR 1.53, 95% CI 1.27 to 1.84) and cleaning products
      (OR 1.55, 95% CI 1.22 to 1.96) out of reach, having syrup of ipecac (OR 3.34, 95%
      CI 1.50 to 7.44) or poison control centre numbers accessible (OR 3.30, 95% CI
      1.70 to 6.39), having fitted stair gates (OR 1.61, 95% CI 1.19 to 2.17), and
      having socket covers on unused sockets (OR 2.69, 95% CI 1.46 to 4.96).
      Interventions providing free, low cost or discounted safety equipment appeared to
      be more effective in improving some safety practices than those interventions not
      doing so. There was no consistent evidence that interventions were less effective
      in families whose children were at greater risk of injury. AUTHORS' CONCLUSIONS:
      Home safety interventions most commonly provided as one-to-one, face-to-face
      education, especially with the provision of safety equipment, are effective in
      increasing a range of safety practices. There is some evidence that such
      interventions may reduce injury rates, particularly where interventions are
      provided at home. Conflicting findings regarding interventions providing safety
      equipment on safety practices and injury outcomes are likely to be explained by
      two large studies; one clinic-based study provided equipment but did not reduce
      injury rates and one school-based study did not provide equipment but did
      demonstrate a significant reduction in injury rates. There was no consistent
      evidence that home safety education, with or without the provision of safety
      equipment, was less effective in those participants at greater risk of injury.
      Further studies are still required to confirm these findings with respect to
      injury rates.

PMID- 23877911
TI  - Commentaries on 'Home safety education and provision of safety equipment for
      injury prevention'.

PMID- 23877912
TI  - Remediating buildings damaged by dampness and mould for preventing or reducing
      respiratory tract symptoms, infections and asthma (Review).
AB  - BACKGROUND: Dampness and mould in buildings have been associated with adverse
      respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture
      damage is a very common problem in private houses, workplaces and public
      buildings such as schools. OBJECTIVES: To determine the effectiveness of
      remediating buildings damaged by dampness and mould in order to reduce or prevent
      respiratory tract symptoms, infections and symptoms of asthma. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2011, Issue 2), which contains the Cochrane Acute Respiratory
      Infections Group's Specialised Register, MEDLINE (1951 to June week 1, 2011),
      EMBASE (1974 to June 2011), CINAHL (1982 to June 2011), Science Citation Index
      (1973 to June 2011), Biosis Previews (1989 to June 2011), NIOSHTIC (1930 to
      November 2010) and CISDOC (1974 to November 2010). SELECTION CRITERIA: Randomised
      controlled trials (RCTs), cluster-RCTs (cRCTs), interrupted time series studies
      and controlled before-after (CBA) studies of the effects of remediating dampness
      and mould in a building on respiratory symptoms, infections and asthma. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      the risk of bias in the included studies. MAIN RESULTS: We included eight studies
      (6538 participants); two RCTs (294 participants), one cRCT (4407 participants)
      and five CBA studies (1837 participants). The interventions varied from thorough
      renovation to cleaning only. We found moderate-quality evidence in adults that
      repairing houses decreased asthma-related symptoms (among others, wheezing (odds
      ratio (OR) 0.64; 95% confidence interval (CI) 0.55 to 0.75) and respiratory
      infections (among others, rhinitis (OR 0.57; 95% CI 0.49 to 0.66)). For children,
      we found moderate-quality evidence that the number of acute care visits (among
      others mean difference (MD) -0.45; 95% CI -0.76 to -0.14)) decreased in the group
      receiving thorough remediation. One CBA study showed very low-quality evidence
      that after repairing a mould-damaged office building, asthma-related and other
      respiratory symptoms decreased. For children and staff in schools, there was very
      low-quality evidence that asthma-related and other respiratory symptoms in mould
      damaged schools were similar to those of children and staff in non-damaged
      schools, both before and after intervention. For children, respiratory infections
      might have decreased after the intervention. AUTHORS' CONCLUSIONS: We found
      moderate to very low-quality evidence that repairing mould-damaged houses and
      offices decreases asthma-related symptoms and respiratory infections compared to
      no intervention in adults. There is very low-quality evidence that although
      repairing schools did not significantly change respiratory symptoms in staff or
      children, pupils' visits to physicians due to a common cold were less frequent
      after remediation of the school. Better research, preferably with a cRCT design
      and with more validated outcome measures, is needed.

PMID- 23877913
TI  - Commentaries on 'Remediating buildings damaged by dampness and mould for
      preventing or reducing respiratory tract symptoms, infections and asthma'.

PMID- 23877914
TI  - Psychological therapies for the treatment of post-traumatic stress disorder in
      children and adolescents (Review).
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is highly prevalent in children
      and adolescents who have experienced trauma and has high personal and health
      costs. Although a wide range of psychological therapies have been used in the
      treatment of PTSD there are no systematic reviews of these therapies in children
      and adolescents. OBJECTIVES: To examine the effectiveness of psychological
      therapies in treating children and adolescents who have been diagnosed with PTSD.
      SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review
      Group's Specialised Register (CCDANCTR) to December 2011. The CCDANCTR includes
      relevant randomised controlled trials from the following bibliographic databases:
      CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE
      (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We also checked reference lists
      of relevant studies and reviews. We applied no date or language restrictions.
      SELECTION CRITERIA: All randomised controlled trials of psychological therapies
      compared to a control, pharmacological therapy or other treatments in children or
      adolescents exposed to a traumatic event or diagnosed with PTSD. DATA COLLECTION
      AND ANALYSIS: Two members of the review group independently extracted data. If
      differences were identified, they were resolved by consensus, or referral to the
      review team. We calculated the odds ratio (OR) for binary outcomes, the
      standardised mean difference (SMD) for continuous outcomes, and 95% confidence
      intervals (CI) for both, using a fixed-effect model. If heterogeneity was found
      we used a random-effects model. MAIN RESULTS: Fourteen studies including 758
      participants were included in this review. The types of trauma participants had
      been exposed to included sexual abuse, civil violence, natural disaster, domestic
      violence and motor vehicle accidents. Most participants were clients of a trauma
      related support service. The psychological therapies used in these studies were
      cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative,
      supportive counselling, and eye movement desensitisation and reprocessing (EMDR).
      Most compared a psychological therapy to a control group. No study compared
      psychological therapies to pharmacological therapies alone or as an adjunct to a
      psychological therapy. Across all psychological therapies, improvement was
      significantly better (three studies, n = 80, OR 4.21, 95% CI 1.12 to 15.85) and
      symptoms of PTSD (seven studies, n = 271, SMD -0.90, 95% CI -1.24 to -0.42),
      anxiety (three studies, n = 91, SMD -0.57, 95% CI -1.00 to -0.13) and depression
      (five studies, n = 156, SMD -0.74, 95% CI -1.11 to -0.36) were significantly
      lower within a month of completing psychological therapy compared to a control
      group. The psychological therapy for which there was the best evidence of
      effectiveness was CBT. Improvement was significantly better for up to a year
      following treatment (up to one month: two studies, n = 49, OR 8.64, 95% CI 2.01
      to 37.14; up to one year: one study, n = 25, OR 8.00, 95% CI 1.21 to 52.69). PTSD
      symptom scores were also significantly lower for up to one year (up to one month:
      three studies, n = 98, SMD -1.34, 95% CI -1.79 to -0.89; up to one year: one
      study, n = 36, SMD -0.73, 95% CI -1.44 to -0.01), and depression scores were
      lower for up to a month (three studies, n = 98, SMD -0.80, 95% CI -1.47 to -0.13)
      in the CBT group compared to a control. No adverse effects were identified. No
      study was rated as a high risk for selection or detection bias but a minority
      were rated as a high risk for attrition, reporting and other bias. Most included
      studies were rated as an unclear risk for selection, detection and attrition
      bias. AUTHORS' CONCLUSIONS: There is evidence for the effectiveness of
      psychological therapies, particularly CBT, for treating PTSD in children and
      adolescents for up to a month following treatment. At this stage, there is no
      clear evidence for the effectiveness of one psychological therapy compared to
      others. There is also not enough evidence to conclude that children and
      adolescents with particular types of trauma are more or less likely to respond to
      psychological therapies than others. The findings of this review are limited by
      the potential for methodological biases, and the small number and generally small
      size of identified studies. In addition, there was evidence of substantial
      heterogeneity in some analyses which could not be explained by subgroup or
      sensitivity analyses. More evidence is required for the effectiveness of all
      psychological therapies more than one month after treatment. Much more evidence
      is needed to demonstrate the relative effectiveness of different psychological
      therapies or the effectiveness of psychological therapies compared to other
      treatments. More details are required in future trials in regards to the types of
      trauma that preceded the diagnosis of PTSD and whether the traumas are single
      event or ongoing. Future studies should also aim to identify the most valid and
      reliable measures of PTSD symptoms and ensure that all scores, total and sub
      scores, are consistently reported.

PMID- 23877915
TI  - Commentary on 'Psychological therapies for the treatment of post-traumatic stress
      disorder in children and adolescents'.

PMID- 23877916
TI  - Cardenolides and bufadienolide glycosides from Kalanchoe tubiflora and evaluation
      of cytotoxicity.
AB  - Two new cardenolides, kalantubolide A (1) and kalantubolide B (2), and two
      bufadienolide glycosides, kalantuboside A (3) and kalantuboside B (4), as well as
      eleven known compounds were isolated and characterized from the EtOH extract of
      Kalanchoe tubiflora. The structures of compounds were assigned based on 1D and 2D
      NMR spectroscopic analyses including HMQC, HMBC, and NOESY. Biological evaluation
      indicated that cardenolides (1-2) and bufadienolide glycosides (3-7) showed
      strong cytotoxicity against four human tumor cell lines (A549, Cal-27, A2058, and
      HL-60) with IC50 values ranging from 0.01 uM to 10.66 uM. Cardenolides (1-2) also
      displayed significant cytotoxicity toward HL-60 tumor cell line. In addition,
      compounds 3, 4, 5, 6, and 7 blocked the cell cycle in the G2/M-phase and induced
      apoptosis in HL-60 cells. 

PMID- 23877918
TI  - Mechanism of the antihypertensive and vasorelaxant effects of the flavonoid
      tiliroside in resistance arteries.
AB  - Hypertension is a leading cause of death and disability globally, and its
      prevalence continues to accelerate. The cardiovascular effects of the flavonoid
      tiliroside have never been reported. In this work, using complementary in vivo
      and in vitro approaches, we describe the antihypertensive effect of tiliroside
      and the underlying mechanisms involved in the reduction of blood pressure.
      Tiliroside (1, 5 or 10 mg/kg) induced a dose-dependent long-lasting decrease in
      blood pressure in conscious DOCA-salt hypertensive rats that was accompanied by
      an increased heart rate. Tiliroside also induced a concentration-dependent
      vasodilation of mesenteric resistance arteries precontracted with phenylephrine.
      Removal of the endothelium or pretreatment of the preparation with L-NAME or
      indomethacin did not modify the vasodilator response for tiliroside. When vessels
      were precontracted with a high K+ (50 mM) solution, tiliroside exhibited a
      vasodilator effect similar to that observed in vessels precontracted with
      phenylephrine. Experiments carried out in nominally Ca2+-free solution showed
      that tiliroside antagonized CaCl2-induced contractions. Moreover, tiliroside
      reduced the rise in intracellular Ca2+ concentration induced by membrane
      depolarization in vascular smooth muscle cells. Finally, tiliroside decreased the
      voltage-activated peak amplitude of the L-type Ca2+ channel current in freshly
      dissociated vascular smooth muscle cells from mesenteric arteries. Altogether,
      our results point to an antihypertensive effect of tiliroside due to a reduction
      in peripheral resistance through blockage of voltage-activated peak amplitude of
      the L-type Ca2+ channel in smooth muscle cells.

PMID- 23877917
TI  - Echinocystic acid isolated from Eclipta prostrata suppresses lipopolysaccharide
      induced iNOS, TNF-alpha, and IL-6 expressions via NF-kappaB inactivation in RAW
      264.7 macrophages.
AB  - In this study, we aimed to identify the compounds in Eclipta prostrata
      responsible for its anti-inflammatory effects using an in vitro bioassay. Three
      triterpenoids, eclalbasaponin I, eclalbasaponin II, and echinocystic acid, were
      isolated from an EtOAc fraction of the 70 % EtOH extract of E. prostrata by
      activity-guided fractionation based on the inhibition of nitric oxide release
      from lipopolysaccharide-induced RAW 264.7 macrophages. Of these three
      triterpenoids, echinocystic acid inhibited lipopolysaccharide-induced production
      of nitric oxide and cytokines such as tumor necrosis factor-alpha and interleukin
      6. Consistent with these observations, echinocystic acid concentration
      dependently inhibited lipopolysaccharide-induced inducible nitric oxide synthase
      expression at the protein level and inducible nitric oxide synthase, tumor
      necrosis factor-alpha, and interleukin-6 expression at the mRNA level, and
      inhibited lipopolysaccharide-induced iNOS promoter binding activity. In addition,
      echinocystic acid suppressed the lipopolysaccharide-induced transcriptional
      activity of nuclear factor-kappaB by blocking the nuclear translocation of p65. 

PMID- 23877919
TI  - Eupatilin, a major flavonoid of Artemisia, attenuates aortic smooth muscle cell
      proliferation and migration by inhibiting PI3K, MKK3/6, and MKK4 activities.
AB  - Eupatilin, a major flavonoid of plants in the genus Artemisia, has been shown to
      exhibit anti-inflammatory, anti-oxidative, and anti-tumor effects. However, the
      potential anti-atherogenic effects of eupatilin and any underlying mechanisms
      have not been investigated. In the present study, we sought to determine the
      effects of eupatilin on phenotypes induced by the growth factor PDGF-BB in human
      aortic smooth muscle cells. Here we show that aortic sprouting as well as PDGF-BB
      induced proliferation and migration of human aortic smooth muscle cells were
      significantly inhibited by eupatilin. We found that eupatilin inhibited PI3K
      activity, causing a direct effect on phosphorylation of the downstream kinases
      Akt and p70S6K. In parallel, eupatilin also inhibited the phosphorylation of
      MKK3/6-p38 MAPK and the MKK4-JNK pathway. Moreover we found that eupatilin
      exhibited stronger inhibition effects on PDGF-BB-induced proliferation and
      migration of human aortic smooth muscle cells than PI3K, p38 MAPK, and JNK
      pathway inhibitors. Taken together, our results indicate that eupatilin is a
      potent anti-atherogenic agent that inhibits PDGF-BB-induced proliferation and
      migration in HASMCs as well as aortic sprouting, which is likely mediated through
      the attenuation of PI3K, MKK3/6, and MKK4 activation. 

PMID- 23877920
TI  - Targeted and untargeted phytochemistry of Ligusticum canbyi: indoleamines,
      phthalides, antioxidant potential, and use of metabolomics as a hypothesis
      generating technique for compound discovery.
AB  - Ligusticum canbyi (J.M. Coult & Rose) is a medicinal understory forest species
      used in traditional rituals and ceremonies for spiritual enlightenment and
      improved mental health. Very little is known about the phytochemical complexity
      or diversity of L. canbyi tissues or extracts. The current study was undertaken
      to determine whether Ligusticum tissues and extracts contain specifically
      targeted biologically active phytochemicals such as: melatonin, serotonin, Z
      ligustilide, E-3-butylidenephthalide, and ferulic acid and to investigate the
      untargeted phytochemical complexity of the entire L. canbyi metabolome. The
      results of these studies identified melatonin and serotonin in roots and shoots
      of L. canbyi and L. porteri. Z-ligustilide, E-butylidenephthalide, and ferulic
      acid were quantified in roots and shoots of L. canbyi. Metabolomic analysis
      detected approximately 34,000 compounds in each L. canbyi extract, and predictive
      analysis suggests the presence of more than 70 putative phthalide metabolites.
      The relative contribution of the known metabolites and the unknown markers to the
      antioxidant potential of root and shoot tissues were compared, and it was
      determined that the majority of the antioxidant capacity could be attributed to
      ferulic acid in the tissues. These data provide new understandings of the
      phytomedicinal composition and potential mechanisms of activity of L. canbyi
      extracts and tissues. 

PMID- 23877921
TI  - Screening of medicinal plants for PPARalpha and PPARgamma activation and
      evaluation of their effects on glucose uptake and 3T3-L1 adipogenesis.
AB  - Medicinal plants are a rich source of ligands for nuclear receptors. The present
      study was aimed to screen a collection of plant extracts for PPARalpha/gamma
      activating properties and identify the active extract that can stimulate cellular
      glucose uptake without enhancing the adipogenesis. A reporter gene assay was
      performed to screen ethanolic extracts of 263 plant species, belonging to 94
      families, for activation of PPARalpha and PPARgamma. Eight extracts showed
      activation of PPARgamma, while 22 extracts showed activation of PPARalpha. The
      extracts of five plants (Daphne gnidium, Illicium anisatum, Juniperus virginiana,
      Terminalia chebula, and Thymelaea hirsuta) showed activation of both PPARalpha
      and PPARgamma and out of them, D. gnidium and T. hirsuta markedly increased
      PPARalpha/gamma protein expression. All five extracts showed an increase in
      cellular glucose uptake. Of the five dual agonists, T. chebula and T. hirsuta did
      not show any increase in differentiation of 3T3-L1 preadipocytes, but I. anisatum
      caused an increase in adipogenesis, while D. gnidium and J. virginiana were toxic
      to adipocytes. The adipogenic effect of rosiglitazone was antagonized by T.
      chebula and T. hirsuta. It was concluded that T. hirsuta and T. chebula retain
      the property of elevating glucose uptake as PPARalpha/gamma dual agonists without
      the undesired side effect of adipogenesis. This is the first report to reveal the
      PPARalpha/gamma dual agonistic action and glucose uptake enhancing property of T.
      hirsuta and T. chebula. 

PMID- 23877922
TI  - In vitro BACE1 inhibitory activity of geraniin and corilagin from Geranium
      thunbergii.
AB  - Generation of amyloid beta peptide through the proteolytic process of amyloid
      precursor protein by beta-secretase and gamma-secretase is a main casual factor
      of Alzheimer's disease, since amyloid beta peptide is a major and crucial
      component of senile plaques in Alzheimer's disease brains. In the process of
      searching for beta-secretase inhibitors from natural resources, the EtOAc soluble
      fraction of Geranium thunbergii exhibited significant beta-secretase inhibitory
      activity. Two compounds, geraniin and corilagin, isolated from the most active
      EtOAc fraction of G. thunbergii, exhibited predominant inhibition against beta
      secretase with IC50 values of 4.0 * 10-6 M and 3.4 * 10-5 M, respectively. Dixon
      plot of geraniin and corilagin demonstrated that the beta-secretase inhibition
      was noncompetitive with the substrate, thus clearly suggesting that these
      compounds might bind either to the beta-secretase subsites or to another
      regulatory domain with Ki values of 2.8 * 10-6 M and 7.9 * 10-5 M, respectively.
      Both compounds exhibited no significant inhibition against alpha-secretase and
      other serine proteases including trypsin and chymotrypsin, showing that they were
      relatively specific and selective inhibitors of beta-secretase. These novel
      findings suggest that geraniin and corilagin from G. thunbergii may be effective
      therapeutic agents for further drug development in Alzheimer's disease.

PMID- 23877923
TI  - 6-C-methyl flavonoids isolated from Pinus densata inhibit the proliferation and
      promote the apoptosis of the HL-60 human promyelocytic leukaemia cell line.
AB  - Three structurally related 6-C-methyl flavonoids isolated from Pinus densata,
      including 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (PD1), 5,7,4'
      trihydroxy-3,8-dimethoxy-6-C-methylflavone (PD2), and 5,7,4'-trihydroxy-3-methoxy
      6-C-methylflavone (PD3), were tested for their ability to inhibit the
      proliferation and promote the apoptosis of the HL-60 human leukaemia cell line.
      Cytotoxicity assays in the HL-60 human cancer cell line demonstrated that 5,4'
      dihydroxy-3,7,8-trimethoxy-6-C-methylflavone exhibited the most potent
      cytotoxicity of the three structurally related 6-C-methyl flavonoids. 5,4'
      Dihydroxy-3,7,8-trimethoxy-6-C-methylflavone inhibited the proliferation of HL-60
      cells in a dose-dependent manner with an IC50 of 7.91 uM (48 h treatment).
      Furthermore, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-induced apoptosis
      was associated with mitochondrial membrane disruption and cytochome c release.
      Flow cytometry analyses revealed an increase in the hypodiploid population in
      5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-treated HL-60 cells. Treatment
      with a concentration of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone that
      induced apoptosis activated caspase-3 but did not activate caspase-1. A caspase-3
      inhibitor (Ac-DEVD-CHO), but not a caspase-1 inhibitor (Ac-YVAD-CHO), reversed
      the cytotoxic effects of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone in HL
      60 cells. These data demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C
      methylflavone effectively induced the apoptosis of HL-60 cells and exhibited
      significant anticancer activity via the mitochondrial caspase-3-dependent
      apoptosis pathway.

PMID- 23877924
TI  - Sesquiterpenes from the roots of Illicium jiadifengpi.
AB  - Two new sesquiterpenes (1, 2) and two new sesquiterpene glycosides (3, 4) with a
      seco-prezizaane skeleton, three new allo-cedrane sesquiterpene glycosides (5-7),
      and a new acorane sesquiterpene (8) as well as 15 known analogues were isolated
      from the roots of Illicium jiadifengpi used for the treatment of rheumatoid
      arthritis. The structures of these compounds were elucidated by extensive
      spectroscopic analysis and chemical methods. The absolute configurations of
      compounds 5-7 were confirmed by CD experiments. The configuration of compound 8
      was assigned by single-crystal X-ray crystallographic analysis and CD
      experiments. Compounds 4, 6, 7, 14, and 23 showed moderate antiviral activities
      against Coxsackie virus B3, and all compounds were inactive when evaluated for
      their cytotoxic activities against five human tumor cell lines and
      neuroprotection. 

PMID- 23877925
TI  - Flexoelectric spectroscopy.
AB  - Flexoelectricity is an increasingly popular subject because it can be extremely
      large in thin films and permits switching of devices in nonpolar (non
      piezoelectric) crystals via application of inhomogeneous stresses. However,
      recent work has been limited to macroscopic measurement of voltage or strain.
      Here, we discuss the vibrational spectroscopy of flexoelectricity as a
      recommended new tool for thin-film characterization, with special emphasis upon
      incommensurate crystals. 

PMID- 23877926
TI  - Clofarabine, idarubicin, and cytarabine (CIA) as frontline therapy for patients
      <=60 years with newly diagnosed acute myeloid leukemia.
AB  - Clofarabine is a second generation nucleoside analogue with activity in adults
      with acute myeloid leukemia (AML). A phase I trial of clofarabine, idarubicin,
      and cytarabine (CIA) in relapsed and refractory AML had shown an overall response
      rate (ORR) of 48%. To explore this combination further, we conducted a phase II
      study of (CIA) in patients with newly diagnosed AML <=60 years. Patients >=18-60
      years with AML and adequate organ function were enrolled. Induction therapy
      consisted of clofarabine (C) 20 mg m-2 IV daily (days 1-5), idarubicin (I) 10 mg
      m-2 IV daily (days 1-3), and cytarabine (A) 1 g m-2 IV daily (days 1-5). Patients
      in remission received up to six consolidation cycles (C 15 mg m-2 * 3, I 8 mg m-2
      * 2, and A 0.75 g m-2 * 3). Fifty-seven patients were evaluable. ORR was 79%.
      With a median follow up of 10.9 months, the median overall survival (OS) was not
      reached, the median event-free survival (EFS) was 13.5 months. Most toxicities
      were <=grade 2. Four week mortality was 2%. In subgroup analysis, patients <=40
      years had better OS (P = 0.04) and EFS (P = 0.04) compared to patients >40 years.
      Compared to historical patients treated with idarubicin and cyarabine (IA), the
      OS and EFS were significantly longer for CIA treated patients. In multivariate
      analysis, CIA retained its favorable impact on OS compared to IA. Thus, CIA is an
      effective and safe therapy for patients <=60 years with newly diagnosed AML.

PMID- 23877927
TI  - Use of glucose solution for the alleviation of gemcitabine-induced vascular pain:
      a double-blind randomized crossover study.
AB  - PURPOSE: Gemcitabine is widely used for chemotherapy in many types of cancers.
      However, vascular pain frequently occurs during its infusion, which can be
      serious enough to cause treatment discontinuation. This study was conducted to
      determine whether dissolution with 5 % glucose solution would relieve vascular
      pain compared with the approved use of saline as the diluent. METHODS: Patients
      with cancer who were treated with weekly gemcitabine were eligible. Vascular pain
      was assessed during two consecutive administrations in a double-blind, randomized
      crossover study. One group was scheduled to receive gemcitabine dissolved in
      saline followed by gemcitabine in 5 % glucose solution. In the other group, 5 %
      glucose solution was followed by saline. The primary endpoint was frequency of
      vascular pain for the total infusions of each solvent and the secondary endpoints
      were intensity, as assessed on a visual analogue scale and duration of vascular
      pain. RESULTS: Eighty-seven patients were randomly assigned to each treatment
      schedule. Frequency of vascular pain was significantly lower with 5 % glucose
      solution compared with saline (40 versus 63 %; p < 0.001). The intensity of
      vascular pain was also reduced with 5 % glucose solution compared with saline
      (mean, 1.3 versus 2.7 points; p < 0.001). There was no significant statistical
      difference in duration of vascular pain between the 5 % glucose solution and
      saline solution groups (mean, 21 versus 18 min; p = 0.420). CONCLUSIONS: The use
      of 5 % glucose solution to dissolve gemcitabine significantly reduced the
      frequency and the intensity of vascular pain compared with the use of saline.

PMID- 23877930
TI  - Green polymer chemistry VIII: synthesis of halo-ester-functionalized
      poly(ethylene glycol)s via enzymatic catalysis.
AB  - Halo-ester-functionalized poly(ethylene glycol)s (PEGs) are successfully prepared
      by the transesterification of alkyl halo-esters with PEGs using Candida
      antarctica lipase B (CALB) as a biocatalyst under the solventless conditions.
      Transesterifications of chlorine, bromine, and iodine esters with tetraethylene
      glycol monobenzyl ether (BzTEG) are quantitative in less than 2.5 h. The
      transesterification of halo-esters with PEGs are complete in 4 h. (1) H and (13)
      C NMR spectroscopy with MALDI-ToF and ESI mass spectrometry confirm the structure
      and purity of the products. This method provides a convenient and "green" process
      to effectively produce halo-ester PEGs. 

PMID- 23877929
TI  - Efficient protocol for backbone and side-chain assignments of large,
      intrinsically disordered proteins: transient secondary structure analysis of 49.2
      kDa microtubule associated protein 2c.
AB  - Microtubule-associated proteins (MAPs) are abundantly present in axons and
      dendrites, and have been shown to play crucial role during the neuronal
      morphogenesis. The period of main dendritic outgrowth and synaptogenesis
      coincides with high expression levels of one of MAPs, the MAP2c, in rats. The
      MAP2c is a 49.2 kDa intrinsically disordered protein. To achieve an atomic
      resolution characterization of such a large protein, we have developed a protocol
      based on the acquisition of two five-dimensional (13)C-directly detected NMR
      experiments. Our previously published 5D CACONCACO experiment (Novacek et al. in
      J Biomol NMR 50(1):1-11, 2011) provides the sequential assignment of the backbone
      resonances, which is not interrupted by the presence of the proline residues in
      the amino acid sequence. A novel 5D HC(CC-TOCSY)CACON experiment facilitates the
      assignment of the aliphatic side chain resonances. To streamline the data
      analysis, we have developed a semi-automated procedure for signal assignments.
      The obtained data provides the first atomic resolution insight into the
      conformational state of MAP2c and constitutes a model for further functional
      studies of MAPs.

PMID- 23877931
TI  - Crystal structure and luminescent properties of a novel high efficiency blue
      orange emitting NaCa2LuSi2O7F2:Ce3+,Mn2+ phosphor for ultraviolet light-emitting
      diodes.
AB  - A series of NaCa2LuSi2O7F2:xCe(3+),yMn(2+) phosphors are firstly prepared by a
      high-temperature solid-state reaction technique. The Rietveld refinement analysis
      confirmed that the obtained phosphors have a pure crystalline phase with
      cuspidine-group structure. NaCa2LuSi2O7F2:xCe(3+),yMn(2+) phosphors can be
      efficiently excited by UV light and have two emission bands at about 410 and 600
      nm. The luminescent properties of the singly-doped samples reveal that the Ce(3+)
      ions occupy two different Lu(3+) sites in the host lattice. We observed an
      efficient energy transfer from the Ce(3+) to Mn(2+) ions. The investigation
      revealed that the mechanism of the energy transfer was a resonant type via a
      nonradiative dipole-quadrupole interaction. The hues can be adjusted and white
      light can be obtained by tuning the concentration of Mn(2+) ions in the codoped
      phosphors through the energy transfer from the Ce(3+) to Mn(2+) ions, hinting a
      promising application of NaCa2LuSi2O7F2:xCe(3+),yMn(2+) as a single-component
      phosphor that can produce white light from UV-based LEDs.

PMID- 23877928
TI  - An overview of tools for the validation of protein NMR structures.
AB  - Biomolecular structures at atomic resolution present a valuable resource for the
      understanding of biology. NMR spectroscopy accounts for 11% of all structures in
      the PDB repository. In response to serious problems with the accuracy of some of
      the NMR-derived structures and in order to facilitate proper analysis of the
      experimental models, a number of program suites are available. We discuss nine of
      these tools in this review: PROCHECK-NMR, PSVS, GLM-RMSD, CING, Molprobity,
      Vivaldi, ResProx, NMR constraints analyzer and QMEAN. We evaluate these programs
      for their ability to assess the structural quality, restraints and their
      violations, chemical shifts, peaks and the handling of multi-model NMR ensembles.
      We document both the input required by the programs and output they generate. To
      discuss their relative merits we have applied the tools to two representative
      examples from the PDB: a small, globular monomeric protein (Staphylococcal
      nuclease from S. aureus, PDB entry 2kq3) and a small, symmetric homodimeric
      protein (a region of human myosin-X, PDB entry 2lw9).

PMID- 23877932
TI  - Effects of beta-lapachone, a new anticancer candidate, on cytochrome P450
      mediated drug metabolism.
AB  - PURPOSE: This study aimed to assess the potential inhibitory effects of beta
      lapachone, a new anticancer candidate, on the activities of the cytochrome P450
      (CYP450) enzymes in vitro. METHODS: Different concentrations of beta-lapachone
      were incubated with human liver microsomes in the presence of CYP isozyme
      specific substrates and NADPH, and the formation of the marker metabolites was
      measured using liquid chromatography-tandem mass spectrometry. In addition, time
      dependent inhibition was examined to characterize the mode of the inhibition.
      RESULTS: beta-Lapachone showed concentration-dependent inhibitory effects on all
      CYP isozymes tested (CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYPC19, CYP2D6, and CYP3A4),
      and its half-maximal inhibitory concentration (IC50) values ranged from 2.6 to
      9.7 MUM. However, beta-lapachone did not appear to modulate CYP450 activities as
      a mechanism-based inactivator. CONCLUSIONS: These results suggest that
      pharmacological drug-drug interactions might occur between beta-lapachone and
      drugs co-administered with it, which are extensively metabolized by CYP450
      enzymes, and thus, careful observation is required in clinical pharmacokinetic
      studies.

PMID- 23877933
TI  - Lateral pharyngoplasty reduces nocturnal blood pressure in patients with
      obstructive sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: To compare the values of 24-hour ambulatory blood pressure
      monitoring (ABPM) in patients with obstructive sleep apnea (OSA), before and
      after lateral pharyngoplasty, and to investigate the influence of pre- and post
      treatment polysomnographic and anthropometric variations on changes in ABPM.
      STUDY DESIGN: Prospective study. METHODS: Arterial blood pressure with 24-hour
      ABPM and nocturnal polysomnography were measured before and 6 months after
      surgery in 18 consecutively evaluated adults with OSA at a tertiary center.
      RESULTS: A total of 83.3% were normotensive patients. Nocturnal measurements
      showed a decrease of 5.3 mmHg in mean arterial pressure (MAP; P = .01), 7.4 mmHg
      in mean arterial systolic pressure (SP; P = .006), and 4.2 mmHg in mean arterial
      diastolic pressure (DP; P = .03), leading to significant reductions in all 24
      hour measurements: 3.6 mmHg in MAP, 4.8 mmHg in SP, and 2.9 mmHg in DP. There
      were also significant mean reductions in the apnea-hypopnea index (AHI), from
      33.5 to 20.9 (P = .02), arousal index, from 31.6 to 16.7 (P = .005), and
      percentage of total sleep time with oxyhemoglobin saturation < 90%, from 10.6% to
      0.9% (P = .008). No correlations were noted between the measurements of arterial
      blood pressure and polysomnographic or anthropometric variations. CONCLUSIONS: In
      this small case series, lateral pharyngoplasty reduced the values obtained in the
      24-hour ABPM due to a significant reduction of blood pressures during sleep in
      patients with OSA 6 months after surgery. Although the patients presented with
      reductions in AHI, arousals, and desaturation time, this was not correlated with
      the improvement in arterial blood pressure.

PMID- 23877936
TI  - Transport in semiconductor nanowire superlattices described by coupled quantum
      mechanical and kinetic models.
AB  - In this paper we develop a kinetic model for the analysis of semiconductor
      superlattices, accounting for quantum effects. The model consists of a Boltzmann
      Poisson type system of equations with simplified Bhatnagar-Gross-Krook
      collisions, obtained from the general time-dependent Schrodinger-Poisson model
      using Wigner functions. This system for superlattice transport is supplemented by
      the quantum mechanical part of the model based on the Ben-Daniel-Duke form of the
      Schrodinger equation for a cylindrical superlattice of finite radius. The
      resulting energy spectrum is used to characterize the Fermi-Dirac distribution
      that appears in the Bhatnagar-Gross-Krook collision, thereby coupling the quantum
      mechanical and kinetic parts of the model. The kinetic model uses the dispersion
      relation obtained by the generalized Kronig-Penney method, and allows us to
      estimate radii of quantum wire superlattices that have the same miniband widths
      as in experiments. It also allows us to determine more accurately the time
      dependent characteristics of superlattices, in particular their current density.
      Results, for several experimentally grown superlattices, are discussed in the
      context of self-sustained coherent oscillations of the current density which are
      important in an increasing range of current and potential applications. 

PMID- 23877937
TI  - More research is needed.

PMID- 23877934
TI  - Voxel-based diffusion tensor imaging of an APP/PS1 mouse model of Alzheimer's
      disease.
AB  - Increasing evidence has demonstrated that white matter (WM) disruptions, due to
      the injury of the axon and myelin, play an important role in the pathogenesis of
      Alzheimer's disease (AD). Diffusion tensor imaging (DTI) is a sensitive modality
      to evaluate the WM integrity in both AD patients and animal models. In this
      study, an advanced DTI modality, employing a 7.0-T magnetic resonance imaging
      system, was used to analyze WM changes across the whole brain of an amyloid
      precursor protein/presenilin 1 (APP/PS1) mouse model. A voxel-based analysis was
      used to compare the quantitative DTI parameters automatically in both APP/PS1
      mice (n = 9) and wild-type (WT) controls (n = 9). After DTI examination, the
      ultrastructure analysis was compared with DTI findings. Compared with WT
      controls, gray matter (GM) areas in APP/PS1 mice such as the cingulate cortex and
      the striatum showed significant fractional anisotropy (FA) and axial diffusivity
      (DA) increase, while the thalamus only showed a significant FA increase (p <
      0.01). Similarly, a significant mean diffusivity, DA, and radial diffusivity
      increase was observed in the bilateral neocortex (p < 0.01). The left hippocampus
      only showed significant FA increase in APP/PS1 mice (p < 0.01). The changes in WM
      regions were detected in the forceps minor of the corpus callosum, the anterior
      part of the anterior commissure, and the internal capsule, with a significant FA
      or DA increase (p < 0.01). Abnormalities derived from diffusion measurements were
      in-line with the ultrastructure findings, including extensive pathological damage
      of the neurons, neutrophils, and vessels. In conclusion, voxel-based diffusion
      tensor imaging can detect diffusion alterations not only in GM but also in WM
      areas in AD models, reflecting the extensive pathological changes of AD.

PMID- 23877938
TI  - Treatment of acute gastroenteritis in children: an overview of systematic reviews
      of interventions commonly used in developed countries.
AB  - BACKGROUND: Acute gastroenteritis (AGE) is an extremely common paediatric
      condition, which results in significant morbidity in children and is a financial
      burden to the society. OBJECTIVE: The purpose of this overview is to critically
      evaluate the evidence currently available in the Cochrane Database of Systematic
      Reviews (CDSR) regarding the efficacy and safety of commonly considered treatment
      options in children with AGE. METHODS: All Cochrane reviews evaluating the
      following treatments in children with AGE were eligible for inclusion: oral
      rehydration therapy, anti-emetics and probiotics. We excluded those focusing on
      the treatment of antibiotic associated or nosocomial diarrhoea, persistent
      (chronic) diarrhoea and the prevention of gastroenteritis. We focused on the
      following outcomes that were selected a priori as clinically important: rate of
      admission to the hospital; length of stay in hospital; rate of return visits;
      administration of intravenous (IV) therapy owing to failure of oral rehydration
      therapy; adverse events and dysnatremia. MAIN RESULTS: Children who received oral
      rehydration therapy had a shorter length of stay in hospital compared with
      children who received IV therapy [mean difference, MD = -1.20 days (-2.38, 
      0.02)]; however, the result was no longer significant when an outlying study was
      removed. Children who received IV therapy were at increased risk of developing
      phlebitis [risk difference, RD= - 0.02 (-0.04, -0.01)], while paralytic ileus was
      more common in children receiving ORT [RD = 0.03 (confidence interval, CI 0.01
      0.05)]. Children who received oral ondansetron had lower hospital admission rates
      to the emergency department (ED) and lower rates of IV rehydration during their
      ED stay compared with children receiving placebo [risk ration, RR = 0.40 (CI 0.19
      0.83) and RR = 0.41 (CI 0.29-0.59), respectively]. Children receiving IV
      ondansetron had lower hospital admission rates to the ED than patients receiving
      placebo [RR = 0.21 (0.05, 0.93)]. Probiotic use amongst children hospitalized
      following AGE reduced the mean duration of hospitalization by 1.12 days (CI 
      1.16, -0.38). CONCLUSIONS: Given that oral rehydration is less invasive than IV
      rehydration with no evidence of important clinical differences, it is the first
      choice for rehydration in children with AGE and mild-to-moderate dehydration. As
      the vast majority of children with AGE do not require IV rehydration, oral
      ondansetron administration to children with significant vomiting should be
      performed to reduce the use of IV rehydration and the need for hospital
      admission. In children deemed too unwell to receive oral rehydration therapy, IV
      ondansetron administration is an option, as its use is associated with lower
      hospital admission rates. Although probiotics appear to be an effective option
      for the treatment of AGE amongst hospitalized children, outpatient data is
      lacking and more studies are urgently needed to determine the optimal organism,
      dosing and duration of treatment.

PMID- 23877939
TI  - Inhaled corticosteroids for cystic fibrosis-are they worth the risk?

PMID- 23877940
TI  - Interventions for promoting reintegration and reducing harmful behaviour and
      lifestyles in street-connected children and young people.
AB  - BACKGROUND: Numbers of street-connected children and young people run into many
      millions worldwide and include children and young people who live or work in
      street environments. Whether or not they remain connected to their families of
      origin, and despite many strengths and resiliencies, they are vulnerable to a
      range of risks and are excluded from mainstream social structures and
      opportunities. OBJECTIVES: To summarise the effectiveness of interventions for
      street-connected children and young people that promote inclusion and
      reintegration and reduce harms. To explore the processes of successful
      intervention and models of change in this area, and to understand how
      intervention effectiveness may vary in different contexts. SEARCH METHODS: We
      searched the following bibliographic databases, from inception to 2012, and
      various relevant non-governmental and organisational websites: Cochrane Central
      Register of Controlled Trials (CENTRAL); MEDLINE and PreMEDLINE; EMBASE and
      EMBASE Classic; CINAHL; PsycINFO; ERIC; Sociological Abstracts; Social Services
      Abstracts; Social Work Abstracts; Healthstar; LILACS; System for Grey literature
      in Europe (OpenGrey); ProQuest Dissertations and Theses; EconLit; IDEAS Economics
      and Finance Research; JOLIS Library Catalog of the holdings of the World Bank
      Group and IMF Libraries; BLDS (British Library for Development Studies); Google,
      Google Scholar. SELECTION CRITERIA: The review included data from harm reduction
      or reintegration promotion intervention studies that used a comparison group
      study design and were all randomised or quasi-randomised studies. Studies were
      included if they evaluated interventions aimed to benefit street-connected
      children and young people, aged 0 to 24 years, in all contexts. DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted data and assessed the
      risk of bias of included studies. Data were extracted on intervention delivery,
      context, process factors, equity and outcomes. Outcome measures were grouped
      according to whether they measured psychosocial outcomes, risky sexual behaviours
      or substance use. A meta-analysis was conducted for some outcomes though it was
      not possible for all due to differences in measurements between studies. Other
      outcomes were evaluated narratively. MAIN RESULTS: We included 11 studies
      evaluating 12 interventions from high income countries. We did not find any
      sufficiently robust evaluations conducted in low and middle income countries
      (LMICs) despite the existence of many relevant programmes. Study quality overall
      was low to moderate and there was great variation in the measurement used by
      studies, making comparison difficult. Participants were drop-in and shelter
      based. We found no consistent results on a range of relevant outcomes within
      domains of psychosocial health, substance misuse and sexual risky behaviours
      despite the many measurements collected in the studies. The interventions being
      evaluated consisted of time limited therapeutically based programmes which did
      not prove more effective than standard shelter or drop-in services for most
      outcomes and in most studies. There were favourable changes from baseline in
      outcomes for most particpants in therapy interventions and also in standard
      services. There was considerable heterogeneity between studies and equity data
      were inconsistently reported. No study measured the primary outcome of
      reintegration or reported on adverse effects. The review discussion section
      included consideration of the relevance of the findings for LMIC settings.
      AUTHORS' CONCLUSIONS: Analysis across the included studies found no consistently
      significant benefit for the 'new' interventions compared to standard services for
      street-connected children and young people. These latter interventions, however,
      have not been rigorously evaluated, especially in the context of LMICs. Robustly
      evaluating the interventions would enable better recommendations to be made for
      service delivery. There is a need for future research in LMICs that includes
      children who are on the streets due to urbanisation, war or migration and who may
      be vulnerable to risks such as trafficking.

PMID- 23877941
TI  - Commentary on 'interventions for promoting re-integration and reducing harmful
      behaviour and lifestyles in street-connected children and young people' with a
      response from the review authors.
AB  - This is a commentary on a Cochrane review, published in the issue of EBCH, first
      published as: Coren E, Hossain R, Pardo Pardo J, Veras MMS, Chakraborty K, Harris
      H, Martin AJ. Interventions for promoting re-integration and reducing harmful
      behaviour and lifestyles in street-connected children and young people. Cochrane
      Database of Systematic Reviews 2013, Issue 2. Art. No.: CD009823. DOI:
      10.1002/14651858.CD009823.pub2.

PMID- 23877942
TI  - Glucocorticoids for the treatment of anaphylaxis.
AB  - BACKGROUND: Anaphylaxis is a serious hypersensitivity reaction that is rapid in
      onset and may result in death. Anaphylaxis guidelines recommend glucocorticoids
      for the treatment of people experiencing anaphylaxis. OBJECTIVES: We sought to
      assess the benefits and harms of glucocorticoid treatment during episodes of
      anaphylaxis. SEARCH METHODS: In our previous version we searched the literature
      until September 2009. In this version we searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE
      (Ovid) (1956 to September 2011), EMBASE (Ovid) (1982 to September 2011), CINAHL
      (EBSCOhost) (to September 2011). We also searched the UK National Research
      Register and websites listing ongoing trials, and contacted international experts
      in anaphylaxis in an attempt to locate unpublished material. SELECTION CRITERIA:
      We planned to include randomized and quasi-randomized controlled trials comparing
      glucocorticoids with any control (either placebo, adrenaline (epinephrine), an
      antihistamine, or any combination of these). DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed articles for inclusion. MAIN RESULTS: We found no
      studies that satisfied the inclusion criteria. AUTHORS' CONCLUSIONS: We are,
      based on this review, unable to make any recommendations for the use of
      glucocorticoids in the treatment of anaphylaxis.

PMID- 23877943
TI  - Commentary on 'glucocorticoids for the treatment of anaphylaxis'.
AB  - This is a commentary on a Cochrane review, published in the issue of EBCH, first
      published as: Choo KJL, Simons FER, Sheikh A. Glucocorticoids for the treatment
      of anaphylaxis. Cochrane Database of Systematic Reviews 2012, Issue 4. Art. No.:
      CD007596. DOI: 10.1002/14651858.CD007596.pub3. 

PMID- 23877944
TI  - Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract
      infections.
AB  - BACKGROUND: Acute respiratory infections (ARIs) comprise a large and
      heterogeneous group of infections including bacterial, viral and other
      aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has
      emerged as a promising marker for the diagnosis of bacterial infections and for
      improving decisions about antibiotic therapy. Several randomised controlled
      trials (RCTs) have demonstrated the feasibility of using procalcitonin for
      starting and stopping antibiotics in different patient populations with acute
      respiratory infections and different settings ranging from primary care to
      emergency departments (EDs), hospital wards and intensive care units (ICUs).
      OBJECTIVES: The aim of this systematic review based on individual patient data
      was to assess the safety and efficacy of using procalcitonin for starting or
      stopping antibiotics over a large range of patients with varying severity of ARIs
      and from different clinical settings. SEARCH METHODS: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the
      Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May
      2011) and EMBASE (1974 to May 2011) to identify suitable trials. SELECTION
      CRITERIA: We included RCTs of adult participants with ARIs who received an
      antibiotic treatment either based on a procalcitonin algorithm or usual
      care/guidelines. Trials were excluded if they exclusively focused on paediatric
      patients or if they used procalcitonin for another purpose than to guide
      initiation and duration of antibiotic treatment. DATA COLLECTION AND ANALYSIS:
      Two teams of review authors independently evaluated the methodology and extracted
      data from primary studies. The primary endpoints were all-cause mortality and
      treatment failure at 30 days. For the primary care setting, treatment failure was
      defined as death, hospitalisation, ARI-specific complications, recurrent or
      worsening infection, and patients reporting any symptoms of an ongoing
      respiratory infection at follow-up. For the ED setting, treatment failure was
      defined as death, ICU admission, re-hospitalisation after index hospital
      discharge, ARI-associated complications, and recurrent or worsening infection
      within 30 days of follow-up. For the ICU setting, treatment failure was defined
      as death within 30 days of follow-up. Secondary endpoints were antibiotic use
      (initiation of antibiotics, duration of antibiotics and total exposure to
      antibiotics (total amount of antibiotic days divided by total number of
      patients)), length of hospital stay for hospitalised patients, length of ICU stay
      for critically ill patients, and number of days with restricted activities within
      14 days after randomisation for primary care patients. For the two co-primary
      endpoints of all-cause mortality and treatment failure, we calculated odds ratios
      (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical
      logistic regression. The hierarchical regression model was adjusted for age and
      clinical diagnosis as fixed-effect. The different trials were added as random
      effects into the model. We fitted corresponding linear regression models for
      antibiotic use. We conducted sensitivity analyses stratified by clinical setting
      and ARI diagnosis to assess the consistency of our results. MAIN RESULTS: We
      included 14 trials with 4221 participants. There were 118 deaths in 2085 patients
      (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control
      patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure
      occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients
      (21.9%). Procalcitonin guidance was not associated with increased mortality or
      treatment failure in any clinical setting, or ARI diagnosis. These results proved
      robust in various sensitivity analyses. Total antibiotic exposure was
      significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4
      (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and
      across all the different clinical settings and diagnoses. AUTHORS' CONCLUSIONS:
      Use of procalcitonin to guide initiation and duration of antibiotic treatment in
      patients with ARI was not associated with higher mortality rates or treatment
      failure. Antibiotic consumption was significantly reduced across different
      clinical settings and ARI diagnoses. Further high-quality research is needed to
      confirm the safety of this approach for non-European countries and patients in
      intensive care. Moreover, future studies should also establish cost-effectiveness
      by considering country-specific costs of procalcitonin measurement and potential
      savings in consumption of antibiotics and other healthcare resources, as well as
      secondary cost savings due to lower risk of side effects and reduced
      antimicrobial resistance.

PMID- 23877945
TI  - Commentaries on 'procalcitonin to initiate or discontinue antibiotics in acute
      respiratory tract infections' with a response from the review authors.
AB  - These are commentaries on a Cochrane review, published in this issue of EBCH,
      first published as: Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma
      L, Luyt CE, Wolff M, Chastre J, Tubach F, Kristoffersen KB, Burkhardt O, Welte T,
      Schroeder S, Nobre V, Wei L, Bhatnagar N, Bucher HC, Briel M. Procalcitonin to
      initiate or discontinue antibiotics in acute respiratory tract infections.
      Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD007498. DOI:
      10.1002/14651858.CD007498.pub2. 

PMID- 23877946
TI  - Prophylactic drug management for febrile seizures in children (Review).
AB  - BACKGROUND: Febrile seizures occurring in a child older than one month during an
      episode of fever affect 2% to 4% of children in Great Britain and the United
      States and recur in 30%. Rapid-acting antiepileptics and antipyretics given
      during subsequent fever episodes have been used to avoid the adverse effects of
      continuous antiepileptic drugs. OBJECTIVES: To evaluate the effectiveness and
      safety of antiepileptic and antipyretic drugs used prophylactically to treat
      children with febrile seizures. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011. Issue 3);
      MEDLINE (1966 to May 2011); EMBASE (1966 to May 2011); Database of Abstracts of
      Reviews of Effectiveness (DARE) (May 2011). No language restrictions were
      imposed. We also contacted researchers in the field to identify continuing or
      unpublished studies. SELECTION CRITERIA: Trials using randomised or quasi
      randomised patient allocation that compared the use of antiepileptic or
      antipyretic agents with each other, placebo or no treatment. DATA COLLECTION AND
      ANALYSIS: Two review authors (RN and MO) independently applied pre-defined
      criteria to select trials for inclusion and extracted the pre-defined relevant
      data, recording methods for randomisation, blinding and exclusions. Outcomes
      assessed were seizure recurrence at 6, 12, 18, 24, 36 months and at age 5 to 6
      years in the intervention and non-intervention groups, and adverse medication
      effects. The presence of publication bias was assessed using funnel plots. MAIN
      RESULTS: Thirty-six articles describing 26 randomised trials with 2740 randomised
      participants were included. Thirteen interventions of continuous or intermittent
      prophylaxis and their control treatments were analysed. Methodological quality
      was moderate to poor in most studies. We could not do a meta-analysis for eight
      of the 13 comparisons due to insufficient numbers of trials. No significant
      benefit for valproate, pyridoxine, intermittent phenobarbitone or ibuprofen
      versus placebo or no treatment was found; nor for diclofenac versus placebo
      followed by ibuprofen, acetominophen or placebo; nor for intermittent rectal
      diazepam versus intermittent valproate, nor phenobarbitone versus intermittent
      rectal diazepam. There was a significant reduction of recurrent febrile seizures
      with intermittent oral diazepam versus placebo with a relative risk (RR) of 0.67
      (95% confidence interval (CI) 0.48 to 0.94) at 24 months), RR of 0.61 (95% CI
      0.15 to 0.89) at 48 months, with no benefit at 6, 12 or 72 months. Phenobarbitone
      versus placebo or no treatment reduced seizures at 6, 12 and 24 months but not at
      18 or 72 month follow up (RR 0.60, 95% CI 0.42 to 0.84 at 6 months; RR 0.59, 95%
      CI 0.46 to 0.75 at 12 months; and RR 0.65, 95% CI 0.49 to 0.88 at 24 months).
      Intermittent rectal diazepam versus no treatment or placebo also reduced seizures
      (RR 0.60, 95% CI 0.41 to 0.86 at 6 months; RR 0.65, 95% CI 0.49 to 0.87 at 12
      months; RR 0.2, 95% CI 0.1 to 0.39 at 18 months; RR 0.36, 95% CI 0.18 to 0.71 at
      36 months), with no benefit at 24 months. Intermittent clobazam compared to
      placebo at 6 months resulted in a RR of 0.09 (95% CI 0.02 to 0.30), an effect
      found against an extremely high (83.3%) recurrence rate in the controls and which
      is a result that needs replication. The recording of adverse effects was
      variable. Lower comprehension scores in phenobarbitone treated children were
      found in two studies. In general, adverse effects were recorded in up to some 30%
      of children in the phenobarbitone treated group and in up to 36% in
      benzodiazepine treated groups. Evidence of publication bias was found in the meta
      analyses of comparisons for phenobarbitone versus placebo (8 studies) at 12
      months but not at 6 months (6 studies); and valproate versus placebo (4 studies)
      at 12 months; with too few studies to identify publication bias for the other
      comparisons. AUTHORS' CONCLUSIONS: No clinically important benefits for children
      with febrile seizures were found for intermittent oral diazepam, phenytoin,
      phenobarbitone, intermittent rectal diazepam, valproate, pyridoxine, intermittent
      phenobarbitone or intermittent ibuprofen, nor for diclofenac versus placebo
      followed by ibuprofen, acetominophen or placebo. Adverse effects were reported in
      up to 30% of children. Apparent benefit for clobazam treatment in one recent
      trial needs to be replicated to be judged reliable. Given the benign nature of
      recurrent febrile seizures, and the high prevalence of adverse effects of these
      drugs, parents and families should be supported with adequate contact details of
      medical services and information on recurrence, first aid management and, most
      importantly, the benign nature of the phenomenon.

PMID- 23877947
TI  - Commentary on 'prophylactic drug management for febrile seizures in children'.
AB  - This is a commentary on a Cochrane review, published in this issue of EBCH, first
      published as: Offringa M, Newton R. Prophylactic drug management for febrile
      seizures in children. Cochrane Database of Systematic Reviews 2012, Issue 4. Art.
      No.: CD003031. DOI: 10.1002/14651858.CD003031.pub2. 

PMID- 23877948
TI  - Propofol versus thiopental sodium for the treatment of refractory status
      epilepticus (Review).
AB  - BACKGROUND: Failure to respond to antiepileptic drugs in uncontrolled seizure
      activity such as refractory status epilepticus (RSE) has led to the use of
      anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete
      control of seizure activity. Thiopental sodium and propofol are popularly used
      for this purpose. Both agents have been found to be effective. However, there is
      substantial lack of evidence as to which of the two drugs is better in terms of
      clinical outcome. OBJECTIVES: To compare the efficacy, adverse effects, and short
      and long-term outcomes of RSE treated with one of the two anaesthetic agents,
      thiopental sodium or propofol. SEARCH METHODS: We searched the Cochrane Epilepsy
      Group Specialized Register (10 May 2012), the Cochrane Central Register of
      Controlled Trials (CENTRAL Issue 4 of 12, The Cochrane Library 2012), and MEDLINE
      (1946 to May week 1, 2012). We also searched (10 May 2012) ClinicalTrials.gov,
      The South Asian Database of Controlled Clinical Trials, and IndMED (a
      bibliographic database of Indian Medical Journals). SELECTION CRITERIA: All
      randomised or quasi-randomised controlled studies (regardless of blinding) of
      control of RSE using either thiopental sodium or propofol. DATA COLLECTION AND
      ANALYSIS: Two review authors screened the search results and reviewed abstracts
      of relevant and eligible trials before retrieving the full text publications.
      MAIN RESULTS: One study was available for review. This study was a small, single
      blind, multicentre trial studying adults with RSE and receiving either propofol
      or thiopental sodium for the control of seizure activity (Rossetti 2011). This
      study showed a wide confidence interval suggesting that the drugs may differ in
      efficacy up to more than two-fold. There was no evidence of a difference between
      the drugs with respect to the outcome measures such as control of seizure
      activity and functional outcome at three months. AUTHORS' CONCLUSIONS: There is
      lack of robust and randomised controlled evidence that can clarify the efficacy
      of propofol and thiopental sodium over each other in the treatment of RSE. There
      is a need for large, randomised controlled trials for this serious condition.

PMID- 23877949
TI  - Electroactive polymers: developments of and perspectives for dielectric
      elastomers.
AB  - We present the development and applications of dielectric elastomers. For the
      last 10 years the significance of this class of polymers has risen as more
      applications seem possible and first products have been commercialized.

PMID- 23877950
TI  - Development of takotsubo cardiomyopathy with severe pulmonary edema before a
      cesarean section.
AB  - Takotsubo cardiomyopathy is an acute syndrome involving apical ballooning and
      consequent dysfunction of the left ventricle. Most cases of left ventricular
      dysfunction resolve within 1 month. We present the case of a 40-year-old woman
      who developed severe heart failure caused by takotsubo cardiomyopathy with severe
      left ventricular dysfunction during the perinatal period. Because of the presence
      of multiple myomas, she was scheduled to undergo a cesarean section under general
      anesthesia. However, after induction of general anesthesia, she had to be
      awakened because of the presence of a difficult airway. Because she exhibited
      insufficient oxygenation, she was transferred to the emergency center. Upon
      hospital admission, she expectorated large amounts of pink sputum, indicating
      severe pulmonary edema. Cesarean section was performed immediately.
      Echocardiography revealed severe left ventricular dysfunction. Full recovery of
      cardiac function required almost 1 month, after which she was discharged from the
      hospital without further complications. This is the first reported case of
      takotsubo cardiomyopathy induced by a failed intubation during a scheduled
      cesarean section. Takotsubo cardiomyopathy usually shows a good prognosis, but if
      this myopathy develops during the perinatal period, it can worsen because of
      excessive preload following the termination of fetoplacental circulation.

PMID- 23877951
TI  - Glycosciences Special Issue of Biopolymers.

PMID- 23877953
TI  - Assessment of Tdap administration rates from 2009 to 2012 at a large urban
      nonteaching hospital.
AB  - Due to the significant rise in pertussis cases reported in 2012, these authors
      investigated the tetanus toxoid, reduced diphtheria toxoid, and acellular
      pertussis (Tdap) vaccine administration at our institution from 2009 to 2012 to
      determine if changes in prescribing practices reflected published updates from
      the Advisory Committee on Immunization Practices (ACIP). A single large, urban,
      private, non-teaching hospital. Documented Tdap vaccines administered from
      January 2009 through December 2012 were retrieved using an electronic data pull.
      The incidence of Tdap vaccine administration was reported as number of events per
      1,000 patient visits. This data pull served to provide the longitudinal context
      to prescribing pattern changes at our facility, which were then compared to ACIP
      vaccination recommendation changes. Tdap administrations increased from 1,365
      vaccinations in 2009 to 3,048 vaccinations in 2012. Tdap vaccine administration
      increased significantly each successive year from 2009 to 2012 from 23.96 +/-
      1.25 to 47.15 +/- 1.63 vaccines per 1,000 patient visits to the facility.
      Confidence intervals did not overlap for consecutive years representing
      statistically significant differences between vaccination rates from year to
      year. Review of Tdap administrations demonstrates a clear and significant
      increase over consecutive years from 2009 to 2012. Over this time period there
      were no institutional initiatives aimed at increasing appropriate Tdap use at our
      institution. This study suggests a correlation between ACIP vaccination
      recommendations and provider prescribing of Tdap, although no definitive
      association can be made. 

PMID- 23877954
TI  - Synthesis of a donor-acceptor diblock copolymer via two mechanistically distinct,
      sequential polymerizations using a single catalyst.
AB  - Treatment of a Ni-terminated poly(3-hexylthiophene) (P3HT), generated in situ
      from 5-chloromagnesio-2-bromo-3-hexylthiophene and Ni(1,3
      bis(diphenylphosphino)propane)Cl2, with a perylene diimide-functionalized
      arylisocyanide monomer effects a chain-extension polymerization to afford a donor
      acceptor diblock copolymer using a single catalyst and in a single reaction
      vessel. The two mechanistically distinct polymerizations proceed in a controlled,
      chain growth fashion, allowing the molecular weight of both the P3HT and
      poly(isocyanide) blocks to be tuned by adjusting the initial monomer-to-catalyst
      ratios. The resulting materials are found to self-assemble into crystalline,
      lamellar stacks of donor and acceptor components in the solid state, and also
      exhibit fluorescence quenching in thin films, properties which poise these
      materials for use in organic photovoltaic applications.

PMID- 23877955
TI  - The multiple causal pathways between performance measures' use and effects.
AB  - In recent decades, there has been a growing interest in the design and
      implementation of systems using public reporting of performance measures to
      improve performance. In their simplest form, such interventions rest on the
      market-based logic of consumers using publicly released information to modify
      their behavior, thereby penalizing poor performers. However, evidence from large
      scale efforts to use public reporting of performance measures as an instrumental
      performance improvement tool suggests that the causal mechanisms involved are
      much more complex. This article offers a typology of four different plausible
      causal pathways linking public reporting of performance measures and performance
      improvement. This typology rests on a variety of conceptual models and a review
      of available empirical evidence. We then use this typology to discuss the core
      elements that need to be taken into account in efforts to use public reporting of
      performance measures as a performance improvement tool. 

PMID- 23877956
TI  - The importance of clinical severity in the measurement of hospital readmission
      rates for Medicare beneficiaries, 1997-2007.
AB  - In the coming years, assessing the impact of efforts to reduce hospital
      readmissions will be important to policy makers and hospitals. To inform such
      assessments, we sought to define preexisting trends in readmission rates for
      patients by level of clinical severity using a difference-in-differences analysis
      of Medicare inpatient claims data from 1997, 2002, and 2007 for patients with
      acute myocardial infarction and congestive heart failure. We also examined trends
      in length of stay, in-hospital mortality, and postdischarge mortality by severity
      level to provide additional context for interpreting readmission rate trends.
      From 1997 to 2007, the difference in readmission rates between the highest and
      lowest severity quartiles increased. Length of stay and in-hospital mortality
      decreased for all patients; however, postdischarge mortality increased for the
      highest-severity patients and decreased for the lowest-severity patients.
      Assessments of recent policy reforms and quality improvement programs should
      account for underlying differential trends in readmission rates based on patient
      severity. 

PMID- 23877957
TI  - Motivators and barriers to using patient experience reports for performance
      improvement.
AB  - Increasingly, patient experience surveys are available to provide performance
      feedback to physician groups. However, limited published literature addresses
      factors influencing use of these reports for performance improvement. To address
      this gap, we conducted semistructured interviews with leaders of Massachusetts
      physician groups. We asked about factors influencing groups' use of performance
      data and report characteristics. Motivating characteristics included having group
      leaders who emphasized a positive patient experience and prioritized patient
      retention; public reporting was not an important motivator for most groups. Full
      physician panels were perceived as a barrier to use of reports. Performance
      reports from a statewide public reporting collaborative were not sufficient for
      the majority of groups, with many seeking external reports. As policy makers
      create financial incentives to support performance improvement, assisting leaders
      to articulate the professional case for patient experience and enhancing the
      content and timing of performance reports may be important. 

PMID- 23877958
TI  - Conservation caring: measuring the influence of zoo visitors' connection to
      wildlife on pro-conservation behaviors.
AB  - Zoos in the 21st century are striving to make effective contributions to
      conservation. Although zoos are extremely popular and host over 600 million
      visitors worldwide, one challenge zoos face is how to effectively engage visitors
      and raise awareness and action for conservation. To this end, zoos commonly rely
      on charismatic megafauna, which have been shown to elicit a connection with zoo
      visitors. However, little is known about how to measure a connection to a species
      or how this connection may influence conservation behaviors. This study had two
      sequential objectives. The first was to develop a scale to measure visitors'
      connection to a species (Conservation Caring). The second was to investigate the
      relationship of Conservation Caring to pro-conservation behaviors, following a
      zoo experience. Pre- (n = 411) and post-visit (n = 452) responses were collected
      from three sites in order to assess the reliability and validity of a scale to
      measure Conservation Caring. Structural equation modeling was used to explore the
      relationship between Conservation Caring and pro-conservation behaviors.
      Conservation Caring was deemed a valid and reliable scale and was a strong
      predictor of species oriented behaviors (beta = 0.62), for example, "adopting" an
      animal, but a weak predictor for biodiversity oriented behaviors (beta = 0.07),
      for example, supporting sustainability policies. Results support the role zoos
      can play in fostering a connection to wildlife and stimulating pro-conservation
      behaviors. Additionally, visitors connected to a wide array of animals. On the
      basis of these results, zoos may recruit a wider assemblage of species as
      potential flagships.

PMID- 23877959
TI  - Advancing universal coverage of healthcare in China: translating political will
      into policy and practice.
AB  - China launched its new health system reform plan in 2009 to advance its universal
      coverage of healthcare, after more than 4 years' consultations and discussions
      with various stakeholders including the public. This paper aims to introduce and
      discuss the context and process of China's current health system reform and
      analyse how political will in China has been translated into policy practice over
      the past decade. The paper also shares the insights of World Health
      Organization's contribution to China's health system reform, as the authors
      advised the Chinese government on the reform options and process. Furthermore,
      the paper describes and discusses key challenges in the implementation of the
      reform plan over the past 3 years and draws lessons for other countries.

PMID- 23877960
TI  - Surgical outcomes of early congenital cholesteatoma: minimally invasive
      transcanal approach.
AB  - OBJECTIVES/HYPOTHESIS: To introduce a simple and alternative surgical technique,
      minimally invasive transcanal myringotomy (MITM), for early stage congenital
      cholesteatoma in children and to evaluate the feasibility and results of MITM for
      management of early stage congenital cholesteatoma with respect to its
      effectiveness and safety. STUDY DESIGN: Retrospective review. METHODS: Between
      August 2008 and September 2012, a total of 36 patients with congenital
      cholesteatoma met the inclusion criteria and were analyzed. Patient medical
      records, including demographic characteristics, intraoperative findings, and
      follow-up records, were reviewed. RESULTS: Subjects consisted of 23 males (64%)
      and 13 females (36%), and the age at operation ranged from 12 months to 6 years
      (mean age = 3 years and 6 months). The number of congenital cholesteatoma was as
      follows: 26 patients at stage I and 10 patients at stage II. The follow-up
      duration was between 12 and 56 months, with an average of 30 months. There were
      no postoperative complications such as tympanic membrane perforation, dizziness,
      or secondary middle ear infection. Among 36 patients who had undergone the MITM
      approach for the treatment of congenital cholesteatoma, five (13.8%) showed
      recurrence and underwent a second-look operation. CONCLUSIONS: On the basis of
      our data, the MITM approach is a useful surgical technique for early stage
      congenital cholesteatoma in children. It has many advantages, in that there is no
      external wound and it is a simple surgical technique that involves easy
      postoperative care, a short operation time and hospitalization period, avoidance
      of serious complications, and easy repeatability for recurrence.

PMID- 23877961
TI  - Stability, elastic properties and fracture toughness of Al0.75X0.75B14 (X=Sc, Ti,
      V, Cr, Y, Zr, Nb, Mo) investigated using ab initio calculations.
AB  - The effect of the transition metal valence electron concentration on the energy
      of formation, effective charge of B icosahedra, elastic properties, surface
      energy and fracture toughness was calculated using density functional theory for
      icosahedral transition metal borides of AlXB14 (X=Sc, Ti, V, Cr, Y, Zr, Nb, Mo).
      Consistent with previous work on AlYB14 (Kolpin et al 2009 J. Phys.: Condens.
      Matter 21 355006) it is shown that phase stability is generally dependent on the
      effective charge of the icosahedral transition metal borides. Also, ionization
      potential and electronegativity are identified as parameters affecting the
      effective charge of B icosahedra suitable for use in predicting the phase
      stability. Al0.75Y0.75B14, Al0.75Sc0.75B14 and Al0.75Zr0.75B14 have been
      identified as promising phases for application as protective coatings as they
      exhibit high phase stability and stiffness combined with a comparatively high
      fracture toughness. 

PMID- 23877962
TI  - Design and activity of novel lactoferrampin analogues against O157:H7
      enterohemorrhagic Escherichia coli.
AB  - Lactoferrampin 265-284 (LFampin 265-284) is a peptide consisting of residues 265
      284 of N1-domain of bovine Lactoferrin (LF). This peptide has several cationic
      groups in the C-terminal lobe, exhibiting an antibacterial activity against a
      wide range of microorganisms. However, LFampin 265-284 exhibits low antimicrobial
      activity against the O157:H7 enterohaemorrhagic Escherichia coli (EHEC O157:H7)
      when compared with Lactoferrin chimera and Lactoferricin. Here, we have designed
      three analogues of LFampin 265-284 based on the distribution of cationic groups,
      hydrophobicity, size, and sequence. Analogues were synthesized by solid phase
      chemistry using Fmoc methodology obtaining peptides with 95% purity. All peptides
      maintain the ability to adopt helical conformations (checked by circular
      dichroism spectra and molecular simulations). Some of these analogues exhibited a
      significant increase in antimicrobial activity by counting colony forming units
      against EHEC O157:H7 compared to native LFampin 265-284, with MIC of 10 and 40 uM
      for 264G-D265K and 264G-D265K/S272R, respectively. The incorporation of a GKLI
      sequence in the N-terminal lobe increased dramatically its antibacterial
      activity, an effect which has been attributed to the addition of cationic groups
      in the N-terminal side that may stabilize the helical conformation of the new
      designed peptides.

PMID- 23877963
TI  - Bimetallic aerogels: high-performance electrocatalysts for the oxygen reduction
      reaction.

PMID- 23877964
TI  - Acyclic diene metathesis polymerization and heck polymer-polymer conjugation for
      the synthesis of star-shaped block copolymers.
AB  - Three- and four-arm star shaped polymers, as well as diblock copolymers, are
      synthesized via acyclic diene metathesis (ADMET) polymerization. This is
      accomplished by using an asymmetric alpha,omega-diene containing a terminal
      double bond and an acrylate, which is polymerized in the presence of
      multifunctional acrylates as selective and irreversible chain transfer agents
      using Hoveyda-Grubbs second generation catalyst. High cross-metathesis
      selectivities are achieved at low temperatures enabling good control over
      molecular weights. Furthermore, additional polyethyleneglycol (PEG) blocks are
      attached to these polymers via Heck coupling of the acrylate end-groups of these
      polymers with aryl iodide functionalized PEG, obtaining three- and four-arm star
      shaped di- and triblock copolymers with molecular weights up to 31 kDa.

PMID- 23877965
TI  - Standing balance tests for screening people with vestibular impairments.
AB  - OBJECTIVES/HYPOTHESIS: To improve the test standards for a version of the Romberg
      test and to determine whether measuring kinematic variables improved its utility
      for screening. STUDY DESIGN: Healthy controls and patients with benign paroxysmal
      positional vertigo, postoperative acoustic neuroma resection, and chronic
      peripheral unilateral weakness were compared. METHODS: Subjects wore Bluetooth
      enabled inertial motion units while standing on the floor or medium-density,
      compliant foam, with eyes open or closed, with head still or moving in pitch or
      yaw. Dependent measures were time to perform each test condition, number of head
      movements made, and kinematic variables. RESULTS: Patients and controls did not
      differ significantly with eyes open or with eyes closed while on the floor. With
      eyes closed, on foam, some significant differences were found between patients
      and controls, especially for subjects older than 59 years. Head movement
      conditions were more challenging than with the head still. Significantly fewer
      patients than controls could make enough head movements to obtain kinematic
      measures. Kinematics indicated that lateral balance control is significantly
      reduced in these patients compared to controls. Receiver operator characteristics
      and sensitivity/specificity analyses showed moderately good differences with
      older subjects. CONCLUSIONS: Tests on foam with eyes closed, with head still or
      moving, may be useful as part of a screening battery for vestibular impairments,
      especially for older people. LEVEL OF EVIDENCE: 3b.

PMID- 23877966
TI  - Behavioral responses of Magellanic Penguins (Spheniscus magellanicus) (Foster) to
      saltwater versus freshwater.
AB  - The most common penguin species found along the coast of Brazil is the Magellanic
      Penguin (Spheniscus magellanicus). These penguins spend most of their time
      foraging for food in the oceans. This information is vital to the maintenance of
      this species in captivity. The goal of this study was to evaluate the behavioral
      response of a group of Magellanic Penguins (S. magellanicus) in two different
      conditions of water--fresh and salt. The work was divided into two phases. First,
      animals were kept in enclosures with access to freshwater. Then they were housed
      with access to saltwater. Behaviors were recorded by scan sampling per interval
      of time, totaling 7,200 records for each animal. The results show that the use of
      saltwater for this group of animals kept in captivity was more effective for
      increasing the time the animals spent in the water, increasing foraging behavior,
      stimulating swimming, and providing display of typical behaviors of the species,
      showing that access to a saltwater environment is an important tool in trying to
      provide well-being for this species in captivity.

PMID- 23877968
TI  - Copper-catalyzed dehydrogenative coupling of arenes with alcohols.

PMID- 23877967
TI  - ATP-driven molecular chaperone machines.
AB  - This review is focused on the mechanisms by which ATP binding and hydrolysis
      drive chaperone machines assisting protein folding and unfolding. A survey of the
      key, general chaperone systems Hsp70 and Hsp90, and the unfoldase Hsp100 is
      followed by a focus on the Hsp60 chaperonin machine which is understood in most
      detail. Cryo-electron microscopy analysis of the E. coli Hsp60 GroEL reveals
      intermediate conformations in the ATPase cycle and in substrate folding. These
      structures suggest a mechanism by which GroEL can forcefully unfold and then
      encapsulate substrates for subsequent folding in isolation from all other binding
      surfaces.

PMID- 23877969
TI  - Anti-Mullerian hormone (AMH), inhibin-alpha, growth differentiation factor 9
      (GDF9), and bone morphogenic protein-15 (BMP15) mRNA and protein are influenced
      by photoperiod-induced ovarian regression and recrudescence in Siberian hamster
      ovaries.
AB  - Exposure of Siberian hamsters to short photoperiod (SD) inhibits ovarian
      function, including folliculogenesis, whereas function is restored with their
      transfer to long photoperiods (LD). To investigate the mechanism of photo
      stimulated recrudescence, we assessed key folliculogenic factors-anti-Mullerian
      hormone (AMH), inhibin-alpha, growth differentiation factor-9 (GDF9), and bone
      morphogenic protein-15 (BMP15)-across the estrus cycle and in photo-regressed and
      recrudescing ovaries. Adult hamsters were exposed to either LD or SD for 14
      weeks, which respectively represent functional and regressed ovaries. Select
      regressed hamsters were transferred back to LD for 2 (post-transfer week 2; PTw2)
      or 8 weeks (PTw8). Ovaries were collected and fixed in formalin for
      immunohistochemistry or frozen in liquid nitrogen for real-time PCR. AMH, inhibin
      alpha, GDF9, and BMP15 mRNA and protein were detected in all stages of the estrus
      cycle. Fourteen weeks of SD exposure increased (P < 0.05) ovarian AMH, GDF9, and
      BMP15, but not inhibin-alpha mRNA levels as compared to LD. Transfer of regressed
      hamsters to stimulatory long photoperiod for 8 weeks returned AMH and GDF9 mRNA
      levels to LD-treated levels, and further increased mRNA levels for inhibin-alpha
      and BMP15. Immunostaining for AMH, inhibin-alpha, GDF9, and BMP15 proteins was
      most intense in preantral/antral follicles and oocytes. The overall
      immunostaining extent for AMH and inhibin-alpha generally mirrored the mRNA data,
      though no changes were observed for GDF9 or BMP15 immunostaining. Shifts in mRNA
      and protein levels across photoperiod conditions suggest possible syncretic roles
      for these folliculogenic factors in photo-stimulated recrudescence via potential
      regulation of follicle recruitment, preservation, and development.

PMID- 23877970
TI  - Performance on the Green Word Memory Test following Operation Enduring
      Freedom/Operation Iraqi Freedom-era military service: Test failure is related to
      evaluation context.
AB  - This study investigates prior reports of high neuropsychological symptom validity
      test (SVT) failure rates in post-deployed Operation Enduring Freedom/Operation
      Iraqi Freedom (OEF/OIF) active and veteran military personnel, using a large,
      multi-site sample (N = 214) drawn from three levels of the Department of
      Defense/Department of Veterans Affairs (VA) Polytrauma System of Care. The sample
      failure rate and its relationship to research versus dual research/clinical
      context of evaluation were examined, in addition to secondary variables explored
      in prior studies. Results yielded an overall failure rate of 25%, lower than
      prior reports describing OEF/OIF active-duty and veteran military personnel.
      Findings also supported the hypothesis that SVT failure rates would differ by
      context (dual > research). Participants with traumatic brain injury (TBI) failed
      more frequently than those without TBI in the dual context but not in the
      research context. Secondary analyses revealed that failure rates increased in the
      presence of depression, posttraumatic stress disorder, and male sex but were
      unrelated to active versus veteran military status, service connection (SC) or
      percentage of SC, age, education, or ethnicity. Further research is required to
      elucidate the underpinnings of these findings in light of the limited literature
      and variability between OEF/OIF-related SVT studies, as well as the substantial
      diagnostic and treatment implications for VA.

PMID- 23877971
TI  - Relevance of hypointense brain MRI lesions for long-term worsening of clinical
      disability in relapsing multiple sclerosis.
AB  - BACKGROUND: The accrual of brain focal pathology is considered a good substrate
      of disability in relapsing-remitting multiple sclerosis (RRMS). However,
      knowledge on long-term lesion evolution and its relationship with disability
      progression is poor. OBJECTIVE: The objective of this paper is to evaluate in
      RRMS the long-term clinical relevance of brain lesion evolution. METHODS: In 58
      RRMS patients we acquired, using the same scanner and protocol, brain magnetic
      resonance imaging (MRI) at baseline and 10+/-0.5 years later. MRI data were
      correlated with disability changes as measured by the Expanded Disability Status
      Scale (EDSS). RESULTS: The annualized 10-year lesion volume (LV) growth was
      +0.25+/-0.5 cm(3) (+6.7+/-8.7%) for T2-weighted (T2-W) lesions and +0.20+/-0.31
      cm(3) (+11.5+/-12.3%) for T1-weighted (T1-W) lesions. The univariate analysis
      showed moderate correlations between baseline MRI measures and EDSS at 10 years
      (p < 0.001). Also, 10-year EDSS worsening correlated with LV growth and the
      number of new/enlarging lesions measured over the same period (p < 0.005). In the
      stepwise multiple regression analysis, EDSS worsening over 10 years was best
      correlated with the combination of baseline T1-W lesion count and increasing T1-W
      LV (R = 0.61, p < 0.001). CONCLUSION: In RRMS patients, long-term brain lesion
      accrual is associated with worsening in clinical disability. This is particularly
      true for hypointense, destructive lesions.

PMID- 23877972
TI  - Natalizumab inhibits the expression of human endogenous retroviruses of the W
      family in multiple sclerosis patients: a longitudinal cohort study.
AB  - BACKGROUND: Several viruses were reported as co-factors triggering the
      pathogenesis of multiple sclerosis (MS), including the endogenous retroviruses of
      the HERV-W family, that were also proposed as biomarkers of disease progression
      and therapy outcome. OBJECTIVE: The objective of this article is to clarify
      whether in MS patients treatment with natalizumab has effects on MSRV/syncytin
      1/HERV-W expression and the possible relationship with disease outcome. METHODS:
      Peripheral blood mononuclear cells were collected from 22 patients with relapsing
      remitting disease, at entry and after three, six and 12 months of treatment with
      natalizumab. The cell subpopulations and the expression of MSRVenv/syncytin
      1/HERV-Wenv were analyzed by flow cytometry and by discriminatory env-specific RT
      PCR assays. RESULTS: By flow cytometry the relative amounts of T, NK and monocyte
      subpopulations were shown to remain fairly constant. A relative increase of B
      lymphocytes was observed at three to six months (p = 0.033). The MSRVenv and
      syncitin-1 transcripts were reduced at six to 12 months of therapy (p = 0.0001).
      Accordingly, at month 12, the plasma-membrane levels of the HERV-Wenv protein
      were reduced (p = 0.0001). B cells, NK and monocytes but not T cells expressed
      the HERV-Wenv protein. None of the patients relapsed during therapy. CONCLUSION:
      Effective therapy with natalizumab downregulates MSRV/syncytin-1/HERV-W
      expression.

PMID- 23877973
TI  - Vascular risk factors, depression, and cognitive change among African American
      older adults.
AB  - OBJECTIVE: Vascular burden has been linked to future depression and cognitive
      change in predominately European American samples. This study investigated these
      relationships in older African Americans. METHODS: To examine the connection
      between vascular risk factors, depression, and cognitive change, this study
      utilized data from 435 older African Americans. Specifically, the study examined
      the link between vascular risk at baseline with depression and cognitive
      functioning at a 2.5-year follow-up visit. RESULTS: High baseline vascular risk
      was associated with increased odds of future depression while controlling for age
      and current depression. A series of path analyses demonstrated links between
      baseline vascular risk, increases in depression, and decreases in processing
      speed. CONCLUSIONS: These findings suggest that African Americans with greater
      vascular burden are at greater risk for depression and cognitive change.

PMID- 23877974
TI  - 18-FDG-PET in the initial staging of sinonasal malignancy.
AB  - OBJECTIVES/HYPOTHESIS: The utility of fluorine-18 fluorodeoxyglucose-positron
      emission tomography (PET) has been gradually defined for most head and neck
      cancers, However, its utility in the initial diagnosis of sinonasal malignancy
      has not been extensively studied. The aim of this study was to determine if PET
      scanning accurately diagnoses and stages malignant sinonasal lesions and if
      maximum standard uptake value (SUV max) correlates with clinically advanced
      disease. STUDY DESIGN: Retrospective chart review. METHODS: There were 51
      patients with sinonasal malignancy who underwent diagnostic whole body PET or PET
      computed tomography scans that were analyzed for patient and disease
      characteristics, SUV max, and staging. RESULTS: Of the 51 patients, 48 scans were
      positive at the primary site, with a sensitivity of 94%. Four patients were found
      to have intensely avid uptake, in which the numerical SUV max was not documented,
      and three patients did not have any uptake in the region of their tumor. Mean SUV
      max at the primary site was 16.1 (range, 3.1-59). Metastasis was detected in 31%
      (16/51) of the patients. There was a potential positive correlation between SUV
      max at the primary site and detection of metastasis on univariate analysis (r =
      0.19, P = .09), but on multivariate analysis, SUV max was not found to correlate
      with T staging or metastasis. CONCLUSIONS: For diagnosis of sinonasal malignancy,
      PET scans have a high sensitivity, although false negatives occurred in 6% of
      cases. PET scanning detected metastasis in 31% of patients, but SUV max did not
      function as a marker for clinically advanced disease. The role of diagnostic PET
      for sinonasal malignancy is currently limited to cases with a high suspicion of
      metastatic disease.

PMID- 23877978
TI  - Sex-specific associations of gestational glucose tolerance with childhood body
      composition.
AB  - OBJECTIVE: To examine the associations of maternal gestational glucose tolerance
      with offspring body composition in late childhood. RESEARCH DESIGN AND METHODS:
      Among 958 women in the prebirth cohort Project Viva, glucose tolerance was
      assessed in the second trimester by nonfasting 50-g 1-h glucose challenge test
      (GCT), followed if abnormal by fasting 100-g 3-h oral glucose tolerance test
      (OGTT). We categorized women as normoglycemic (83.3%) if GCT was <=140 mg/dL,
      isolated hyperglycemia (9.1%) if GCT was abnormal but OGTT normal, intermediate
      glucose intolerance (IGI) (3.3%) if there was one abnormal value on OGTT, or
      gestational diabetes mellitus (GDM) (4.5%) if there were two or more abnormal
      OGTT values. Using multivariable linear regression, we examined adjusted
      associations of glucose tolerance with offspring overall (N=958) and central
      (N=760) adiposity and body composition using dual X-ray absorptiometry (DXA)
      measured at the school-age visit (95+/-10 months). RESULTS: Compared with that in
      the male offspring of normoglycemic mothers, DXA fat mass was higher in male
      offspring of GDM mothers (1.89 kg [95% CI 0.33-3.45]) but not in male offspring
      of mothers with IGI (0.06 kg [-1.45 to 1.57]). DXA trunk-to-peripheral fat mass,
      a measure of central adiposity, was also somewhat higher in male offspring of GDM
      mothers (0.04 [-0.01 to 0.09]). In girls, DXA fat mass was higher in offspring of
      mothers with IGI (2.23 kg [0.12-4.34]) but not GDM (-1.25 kg [-3.13 to 0.63]). We
      showed no association of gestational glucose tolerance with DXA lean mass.
      CONCLUSIONS: In this study, only male offspring of GDM mothers manifested
      increased adiposity, whereas only female offspring of mothers with IGI did so.
      Sex differences in glycemic sensitivity may explain these findings.

PMID- 23877979
TI  - Categorical analysis of the impact of aerobic and resistance exercise training,
      alone and in combination, on cardiorespiratory fitness levels in patients with
      type 2 diabetes: results from the HART-D study.
AB  - OBJECTIVE: Low cardiorespiratory fitness (CRF) is an independent risk factor for
      cardiovascular disease (CVD), especially in individuals with type 2 diabetes. Age
      predicted, sex-stratified, and maximal MET cut points have been developed to
      determine the risk of CVD events and mortality in low CRF categories. We examined
      the proportion of Health Benefits of Aerobic and Resistance Training in
      Individuals With Type 2 Diabetes (HART-D) participants above these cut points
      before and after 9 months of aerobic training (AT), resistance training (RT), or
      a combination of both (ATRT). RESEARCH DESIGN AND METHODS: Participants from the
      HART-D study (n=196) who were randomly assigned to exercise training (AT, RT, or
      ATRT) or to a nonexercise control group between April 2007 and August 2009 were
      used in this ancillary study. Cut points were previously established for age
      predicted METs (>100% and >85%, mean and increased CVD risk, respectively), age-
      and sex-stratified METs (Aerobic Center Longitudinal Study), and clinically
      discernible METs (men>8.0, women>6.5). RESULTS: Baseline prevalence of
      participants above these cut points was similar for all intervention groups
      (P>0.50) and ranged from 11.9% (>100% age predicted) to 55.1% (>85% age
      predicted). Baseline prevalence and age-, sex-, and race/ethnic group-adjusted
      percentage of participants above each cut point increased significantly after AT
      and ATRT (P<0.05 for all). CONCLUSIONS: Structured exercise training, especially
      the AT component, was associated with a greater number of participants moving
      above established cut points indicative of low CRF. These results have public
      health and clinical implications for the growing number of patients with type 2
      diabetes at high risk for CVD.

PMID- 23877980
TI  - Challenges to healthy eating for people with diabetes in a low-income, minority
      neighborhood.
AB  - OBJECTIVE: This study used qualitative interviews with black and Latino
      participants with diabetes to further understanding about types of foods eaten,
      food preparation, sources of foods and meals, communication with providers, and
      effects of race and ethnicity on eating in this population. RESEARCH DESIGN AND
      METHODS: Researchers recruited black and Latino adults from East Harlem, New
      York, to participate in four English and Spanish focus groups. Discussions were
      transcribed, coded, and analyzed to uncover prevalent themes, which were
      interpreted with the Common Sense Model of Self-Regulation. RESULTS: Thirty-seven
      adults with diabetes participated in four focus groups. The following four major
      themes emerged from the analyses: 1) The food environment limited participants'
      access to healthy foods; 2) understanding of diabetes and communication with
      clinicians about healthy eating was limited and abstract; 3) the short-term,
      negative consequences of healthy eating outweighed the benefits; and 4) stress,
      in large part from poverty and discrimination, was seen as a causal factor for
      both poor eating and diabetes. CONCLUSIONS: Participants' responses indicated
      that using healthy eating to control diabetes does not provide immediate,
      tangible results. Thus, these participants followed their own common sense to
      guide their diabetes management and improve their health. Clinicians may be
      better able to help patients eat healthfully if they consider these factors
      during medical visits.

PMID- 23877981
TI  - Risk of a recurrent cardiovascular event in individuals with type 2 diabetes or
      intermediate hyperglycemia: the Hoorn Study.
AB  - OBJECTIVE: To investigate risk of a recurrent cardiovascular event and its
      predictors in a population-based cohort. RESEARCH DESIGN AND METHODS:
      Participants of the Hoorn Study who had experienced a first cardiovascular event
      after baseline (n = 336) were followed with respect to a recurrent event.
      Absolute risk of a recurrent event was calculated for individuals with normal
      glucose metabolism, intermediate hyperglycemia, and type 2 diabetes. Cox
      regression models were used to investigate which variables, measured before the
      first vascular event, predicted a recurrent event using the stepwise backward
      procedure. RESULTS: During a median follow-up of 4.1 years, 44% (n = 148) of the
      population developed a recurrent vascular event. The rate of recurrent events per
      100 person-years was 7.2 (95% CI 5.8-8.7) in individuals with normal glucose
      metabolism, compared with 9.8 (6.6-14.0) in individuals with intermediate
      hyperglycemia and 12.5 (8.5-17.6) in individuals with type 2 diabetes. Higher age
      (hazard ratio 1.02 [95% CI 1.00-1.04]), male sex (1.56 [1.08-2.25]), waist
      circumference (1.02 [1.02-1.03]), higher systolic blood pressure (1.01 [1.01
      1.02]), higher HbA1c (%, 1.13 [0.97-1.31]/ mmol/mol, 1.01 [1.00-1.03]), and
      family history of myocardial infarction (1.38 [0.96-2.00]) predicted a recurrent
      cardiovascular event. CONCLUSIONS: Individuals with type 2 diabetes, but not
      individuals with intermediate hyperglycemia, are at increased risk for a
      recurrent vascular event compared with individuals with normal glucose
      metabolism. In people with a history of cardiovascular disease, people at
      increased risk of a recurrent event can be identified based on the patient's risk
      profile before the first event.

PMID- 23877982
TI  - Clinical inertia in people with type 2 diabetes: a retrospective cohort study of
      more than 80,000 people.
AB  - OBJECTIVE: To determine time to treatment intensification in people with type 2
      diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and
      associated levels of glycemic control. RESEARCH DESIGN AND METHODS: This was a
      retrospective cohort study based on 81,573 people with type 2 diabetes in the
      U.K. Clinical Practice Research Datalink between January 2004 and December 2006,
      with follow-up until April 2011. RESULTS: In people with HbA1c >=7.0, >=7.5, or
      >=8.0% (>=53, >=58, or >=64 mmol/mol), median time from above HbA1c cutoff to
      intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively,
      for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two
      OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years
      for those taking one, two, or three OADs. Mean HbA1c at intensification with an
      OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%.
      In patients taking one, two, or three OADs, median time from treatment initiation
      to intensification with an OAD or insulin exceeded the maximum follow-up time of
      7.2 years. The probability of patients with poor glycemic control taking one,
      two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1-43.6%
      and with insulin 5.1-12.0%. CONCLUSIONS: There are delays in treatment
      intensification in people with type 2 diabetes despite suboptimal glycemic
      control. A substantial proportion of people remain in poor glycemic control for
      several years before intensification with OADs and insulin.

PMID- 23877983
TI  - Corneal nerve loss detected with corneal confocal microscopy is symmetrical and
      related to the severity of diabetic polyneuropathy.
AB  - OBJECTIVE: To establish if corneal nerve loss, detected using in vivo corneal
      confocal microscopy (IVCCM), is symmetrical between right and left eyes and
      relates to the severity of diabetic neuropathy. RESEARCH DESIGN AND METHODS:
      Patients (n = 111) with type 1 and type 2 diabetes and 47 age-matched healthy
      control subjects underwent detailed assessment and stratification into no (n =
      50), mild (n = 26), moderate (n = 17), and severe (n = 18) neuropathy. IVCCM was
      performed in both eyes and corneal nerve fiber density (CNFD), branch density
      (CNBD), and fiber length (CNFL) and the tortuosity coefficient were quantified.
      RESULTS: All corneal nerve parameters differed significantly between diabetic
      patients and control subjects and progressively worsened with increasing severity
      of neuropathy. The reduction in CNFD, CNBD, and CNFL was symmetrical in all
      groups except in patients with severe neuropathy. CONCLUSIONS: IVCCM
      noninvasively detects corneal nerve loss, which relates to the severity of
      neuropathy, and is symmetrical, except in those with severe diabetic neuropathy.

PMID- 23877984
TI  - Subarachnoid hemorrhage in type 1 diabetes: a prospective cohort study of 4,083
      patients with diabetes.
AB  - OBJECTIVE: To estimate for the first time the incidence of subarachnoid
      hemorrhage (SAH) in type 1 diabetes. RESEARCH DESIGN AND METHODS: Using the
      nationwide Finnish Diabetic Nephropathy (FinnDiane) Study cohort of 4,083
      patients with type 1 diabetes (mean age of 37.4 +/- 11.8 years at enrollment), we
      analyzed the incidence of first-ever SAH events. RESULTS: During the follow-up
      time of 36,680 person-years (median 9.4 years), 15 patients with type 1 diabetes
      experienced an aneurysmal or nonaneurysmal SAH, and thus the crude incidence of
      SAH was 40.9 (95% CI 22.9-67.4) per 100,000 person-years. One patient had a
      verified aneurysmal SAH, and four patients died suddenly of an SAH, which was
      most likely caused by an aneurysm. SAHs in 10 out of 15 patients were classified
      as nonaneurysmal SAH, and thus the crude incidence of nonaneurysmal SAH was 27.3
      (13.1-50.1) per 100,000 person-years. None of the nonaneurysmal SAHs were fatal.
      In univariate analysis, current smokers had a hazard ratio of 4.82 (95% CI 1.31
      17.81) for nonaneurysmal SAH. CONCLUSIONS: The incidence of nonaneurysmal SAH is
      high among patients with type 1 diabetes. Our findings suggest that nonaneurysmal
      SAH is a distinct new microvascular complication in type 1 diabetes.

PMID- 23877985
TI  - New-onset diabetes in elderly subjects: association between HbA1c levels,
      mortality, and coronary revascularization.
AB  - OBJECTIVE: New-onset diabetes mellitus (DM) in elderly patients is associated
      with increased risk of diabetes complications and mortality. It is unknown
      whether glycemic control in this population influences the mortality risk.
      RESEARCH DESIGN AND METHODS: The current study was conducted using the
      computerized database of the Sharon-Shomron District of Clalit Health Services in
      Israel. Included in the study were subjects 65 years of age and above with new
      onset DM. The primary outcome measures were all-cause mortality and coronary
      revascularization procedures with either percutaneous coronary intervention or
      coronary artery bypass grafting. RESULTS: Participants (n = 2,994) were
      stratified into four groups according to their mean HbA1c levels during the
      follow-up period (<6.5% [48 mmol/mol], 6.5-6.99% [48-52 mmol/mol], 7-7.49% [53-57
      mmol/mol], and >=7.5% [58 mmol/mol]). During a mean follow-up of 5.54 +/- 2.1
      years, 1,173 (39.17%) participants died and 285 (9.51%) underwent coronary
      revascularization. An HbA1c level >7.5% (58 mmol/mol) was associated with a
      significantly increased all-cause mortality rate (hazard ratio [HR] 1.74 [95% CI
      1.2-1.8], P < 0.0001). This difference remained statistically significant after a
      multivariate model adjusted for the conventional cardiovascular risk factors and
      for the use of hypoglycemic agents and statins. Kaplan-Meier survival plots
      revealed lower survival rates in this group of patients. Coronary
      revascularization rates were highest among subjects with HbA1c 6.5-6.99% (48-52
      mmol/mol) (HR 1.6 [1.01-2.4], P < 0.05) and lowest in patients with HbA1c >=7.5%
      (58 mmol/mol). CONCLUSIONS: An HbA1c level >7.5% (58 mmol/mol) is associated with
      increased risk for all-cause mortality and with a lower revascularization rate in
      elderly patients with new-onset DM.

PMID- 23877986
TI  - Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic
      patients.
AB  - OBJECTIVE: To investigate the relationship of circulating matrix Gla protein
      (MGP) species with incident cardiovascular disease (CVD) or coronary heart
      disease (CHD) in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: EPIC-NL
      is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993
      1997), 518 participants were known to have type 2 diabetes. MGP levels were
      measured by ELISA techniques in baseline plasma samples. The incidence of fatal
      and nonfatal CVD and CVD subtypes-CHD, peripheral arterial disease (PAD), heart
      failure, and stroke-were obtained by linkage to national registers. Cox
      proportional hazard models were used to calculate hazard ratios (HRs), adjusted
      for sex, waist-to-hip ratio, physical activity, and history of CVD. RESULTS:
      During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher
      circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly
      associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95% CI 1.06
      1.38), PAD (HRSD 1.32 [95% CI 1.07-1.65]), and heart failure (HRSD 1.75 [95% CI
      1.42-2.17]) after adjustment. Higher circulating dp-ucMGP levels were not related
      to risk of CHD (HRSD 1.12 [95% CI 0.94-1.34]) or stroke (HRSD 1.05 [95% CI 0.73
      1.49]). Circulating desphospho-carboxylated MGP and circulating total
      uncarboxylated MGP levels were not associated with CVD or CVD subtypes.
      CONCLUSIONS: High dp-ucMGP levels were associated with increased CVD risk among
      type 2 diabetic patients, especially with the subtypes PAD and heart failure,
      while other MGP species were not related to CVD risk. These results suggest that
      a poor vitamin K status is associated with increased CVD risk.

PMID- 23877987
TI  - Prognostic impact of aortic stiffness in high-risk type 2 diabetic patients: the
      Rio deJaneiro Type 2 Diabetes Cohort Study.
AB  - OBJECTIVE: The prognostic importance of carotid-femoral pulse wave velocity
      (PWV), the gold standard measure of aortic stiffness, has been scarcely
      investigated in type 2 diabetes and never after full adjustment for potential
      confounders. The aim was to evaluate the prognostic impact of carotid-femoral PWV
      for cardiovascular morbidity and all-cause mortality in a cohort of 565 high-risk
      type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Clinical, laboratory,
      ambulatory blood pressure (BP) monitoring, and carotid-femoral PWV data were
      obtained at baseline. The primary end points were a composite of fatal and
      nonfatal cardiovascular events and all-cause mortality. Multiple Cox survival
      analysis was used to assess the associations between carotid-femoral PWV, as a
      continuous variable and categorized at 10 m/s, and the end points. RESULTS: After
      a median follow-up of 5.75 years, 88 total cardiovascular events and 72 all-cause
      deaths occurred. After adjustments for potential cardiovascular risk factors,
      including micro- and macrovascular complications, ambulatory BP, and metabolic
      control, carotid-femoral PWV was predictive of the composite end point but not of
      all-cause mortality both as a continuous variable (hazard ratio 1.13 [95% CI 1.03
      1.23], P = 0.009 for increments of 1 m/s) and as categorized at 10 m/s (1.92
      [1.16-3.18], P = 0.012). On sensitivity analysis, carotid-femoral PWV was a
      better predictor of cardiovascular events in younger patients (<65 years), in
      those with microvascular complications, and in those with poorer glycemic control
      (HbA1c >=7.5% [58.5 mmol/mol]). CONCLUSIONS: Carotid-femoral PWV provides
      cardiovascular risk prediction independent of standard risk factors, glycemic
      control, and ambulatory BPs and improves cardiovascular risk stratification in
      high-risk type 2 diabetes.

PMID- 23877988
TI  - Safety and efficacy of sitagliptin therapy for the inpatient management of
      general medicine and surgery patients with type 2 diabetes: a pilot, randomized,
      controlled study.
AB  - OBJECTIVE: This study investigated the safety and efficacy of sitagliptin
      (Januvia) for the inpatient management of type 2 diabetes (T2D) in general
      medicine and surgery patients. RESEARCH DESIGN AND METHODS: In this pilot,
      multicenter, open-label, randomized study, patients (n = 90) with a known history
      of T2D treated with diet, oral antidiabetic agents, or low total daily dose of
      insulin (<=0.4 units/kg/day) were randomized to receive sitagliptin alone or in
      combination with glargine insulin (glargine) or to a basal bolus insulin regimen
      (glargine and lispro) plus supplemental (correction) doses of lispro. Major study
      outcomes included differences in daily blood glucose (BG), frequency of treatment
      failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG
      >240 mg/dL), and hypoglycemia between groups. RESULTS: Glycemic control improved
      similarly in all treatment groups. There were no differences in the mean daily BG
      after the 1st day of treatment (P = 0.23), number of readings within a BG target
      of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and
      number of treatment failures (P > 0.99). The total daily insulin dose and number
      of insulin injections were significantly less in the sitagliptin groups compared
      with the basal bolus group (both P < 0.001). There were no differences in length
      of hospital stay (P = 0.78) or in the number of hypoglycemic events between
      groups (P = 0.86). CONCLUSIONS: Results of this pilot indicate that treatment
      with sitagliptin alone or in combination with basal insulin is safe and effective
      for the management of hyperglycemia in general medicine and surgery patients with
      T2D.

PMID- 23877989
TI  - HbA1c and the risks for all-cause and cardiovascular mortality in the general
      Japanese population: NIPPON DATA90.
AB  - OBJECTIVE: Associations between HbA1c and cardiovascular diseases (CVD) have been
      reported mainly in Western countries. It is not clear whether HbA1c measurements
      are useful for assessing CVD mortality risk in East Asian populations. RESEARCH
      DESIGN AND METHODS: The risk for cardiovascular death was evaluated in a large
      cohort of participants selected randomly from the overall Japanese population. A
      total of 7,120 participants (2,962 men and 4,158 women; mean age 52.3 years) free
      of previous CVD were followed for 15 years. Adjusted hazard ratios (HRs) and 95%
      CIs among categories of HbA1c (<5.0%, 5.0-5.4%, 5.5-5.9%, 6.0-6.4%, and >=6.5%)
      for participants without treatment for diabetes and HRs for participants with
      diabetes were calculated using a Cox proportional hazards model. RESULTS: During
      the study, there were 1,104 deaths, including 304 from CVD, 61 from coronary
      heart disease, and 127 from stroke (78 from cerebral infarction, 25 from cerebral
      hemorrhage, and 24 from unclassified stroke). Relations to HbA1c with all-cause
      mortality and CVD death were graded and continuous, and multivariate-adjusted HRs
      for CVD death in participants with HbA1c 6.0-6.4% and >=6.5% were 2.18 (95% CI
      1.22-3.87) and 2.75 (1.43-5.28), respectively, compared with participants with
      HbA1c <5.0%. Similar associations were observed between HbA1c and death from
      coronary heart disease and death from cerebral infarction. CONCLUSIONS: High
      HbA1c levels were associated with increased risk for all-cause mortality and
      death from CVD, coronary heart disease, and cerebral infarction in general East
      Asian populations, as in Western populations.

PMID- 23877990
TI  - Impact of specific glucose-control strategies on microvascular and macrovascular
      outcomes in 58,000 adults with type 2 diabetes.
AB  - OBJECTIVE: Comparative effectiveness research methods are used to compare the
      effect of four distinct glucose-control strategies on subsequent myocardial
      infarction and nephropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS: A
      total of 58,000 adults with type 2 diabetes and A1C <7% (53 mmol/mol) while
      taking two or more oral agents or basal insulin had subsequent A1C >=7% (53
      mmol/mol) to 8.5% (69 mmol/mol). Follow-up started on date of first A1C >=7% and
      ended on date of a specific clinical event, death, disenrollment, or study end.
      Glucose-control strategies were defined as first intensification of glucose
      lowering therapy at A1C >=7, >=7.5, >=8, or >=8.5% with subsequent control for
      treatment adherence. Logistic marginal structural models were fitted to assess
      the discrete-time hazards for each dynamic glucose-control strategy, adjusting
      for baseline and time-dependent confounding and selection bias through inverse
      probability weighting. RESULTS: After adjustment for age, sex, race/ethnicity,
      comorbidities, blood pressure, lipids, BMI, and other covariates, progressively
      more aggressive glucose-control strategies were associated with reduced onset or
      progression of albuminuria but not associated with significant reduction in
      occurrence of myocardial infarction or preserved renal function based on
      estimated glomerular filtration rate over 4 years of follow-up. CONCLUSIONS: In a
      large representative cohort of adults with type 2 diabetes, more aggressive
      glucose-control strategies have mixed short-term effects on microvascular
      complications and do not reduce the myocardial infarction rate over 4 years of
      follow-up. These findings are consistent with the results of recent clinical
      trials, but confirmation over longer periods of observation is needed.

PMID- 23877991
TI  - Cancer incidence among those initiating insulin therapy with glargine versus
      human NPH insulin.
AB  - OBJECTIVE: To add to the evidence on comparative long-term effects of insulin
      analog glargine versus human NPH insulin on the risk for cancer. RESEARCH DESIGN
      AND METHODS: We identified cohorts of initiators of glargine and human NPH
      without an insulin prescription during the prior 19 months among patients covered
      by the Inovalon Medical Outcomes Research for Effectiveness and Economics
      Registry (MORE2 Registry) between January 2003 and December 2010. Patients were
      required to have a second prescription of the same insulin within 180 days and to
      be free of cancer. We balanced cohorts on risk factors for cancer outcomes based
      on comorbidities, comedication, and health care use during the prior 12 months
      using inverse probability of treatment weighting. Incident cancer was defined as
      having two claims for cancer (any cancer) or the same cancer (breast, prostate,
      colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95%
      CI using weighted Cox models censoring for stopping, switching, or augmenting
      insulin treatment, end of enrollment, and mortality. RESULTS: More patients
      initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were
      followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178)
      developed cancer. The overall HR was 1.12 (95% CI 0.95-1.32). Results were
      consistent for breast cancer, prostate cancer, and colon cancer; various
      durations of treatment; and sensitivity analyses. CONCLUSIONS: Patients
      initiating insulin glargine rather than NPH do not seem to be at an increased
      risk for cancer. While our study contributes significantly to our evidence base
      for long-term effects, this evidence is very limited mainly based on actual
      dynamics in insulin prescribing.

PMID- 23877992
TI  - The role of culture and language in avoiding misinformation: pilot findings.
AB  - In two pilot studies, we investigate the possibility that patterns in our
      linguistic environment affect the likelihood of accepting misinformation.
      Turkish, which marks its verbs for the source of a speaker's evidence (first-hand
      perception vs. hearsay), was contrasted with English which does not mark its
      verbs but which, to signal strength of evidence, must employ optional lexical
      marking. In the first pilot study, Turkish adults were shown to be affected by
      that language's obligatory evidential markings: their free recall for details of
      the events changed as a function of the type of the tense-aspect marker in use,
      and strong evidential markers led to increased levels of suggestibility when
      employed with misleading questions. In the second pilot study, Turkish- and
      English-speaking children were shown to be differentially suggestible depending
      on combinations of evidential markers in the story presented and the evidential
      marker employed in the misinformation subsequently provided. Together, these two
      pilot studies show promise in this area of research, which has been ignored by
      the forensic community and yet would seem to be relevant when interviewing,
      taking statements, and giving testimony in cross-linguistic settings.

PMID- 23877993
TI  - Expression dynamics of pluripotency genes in chicken primordial germ cells before
      and after colonization of the genital ridges.
AB  - Mammalian species utilize an inductive mechanism of germ cell specification,
      diverting the fate of some of somatic cells toward pluripotency and germ-cell
      totipotency. It is not known if avian species utilize a similar mechanism nor if,
      analogous to mammalian primordial germ cells (PGCs), pluripotency genes are
      continuously upregulated in migrating and genital ridge-colonizing avian PGCs.
      Thus, this study was conducted to quantify and to analyze the expression profile
      of pluripotency genes at different stages of chicken PGCs development at
      Hamburger and Hamilton (HH) stage 14, when the majority of PGCs have entered into
      the bloodstream; at HH stage 18, when PGCs have resided for 8-12 hr in the
      bloodstream; and at HH stage 28, when the majority of PGCs are found in the
      genital ridge. The transcription for Oct4, Sox2, and Nanog continuously decreased
      from HH stage 14 to HH stage 28. In addition, equal amounts of total RNA could be
      isolated from chicken PGCs at each stage of development, indicating that the
      observed drop of transcription of pluripotency genes is not a consequence of
      transcriptional repression in general. Decreased expression for all three
      proteins was also observed at HH stage 28. Furthermore, in comparison to blood
      PGCs, those residing in the gonad have lost their full capacity for colony
      formation. Our results indicate that, in contrast to mammalian PGCs, chicken PGCs
      continuously downregulate the expression of pluripotency genes and show a
      progressive loss of pluripotency-associated features during different stages of
      germ-line migration.

PMID- 23877994
TI  - Orientational fluctuations near the smectic A to smectic C phase transition in
      two "de Vries"-type liquid crystals.
AB  - On the basis of thorough analysis of 2D X-ray diffraction patterns from smectic
      monodomains, we examine the influence of orientational fluctuations on the weakly
      first-order smectic A (SmA) to smectic C (SmC) transitions in two nonchiral
      organosiloxane "de Vries"-type liquid crystals. We find that these materials
      exhibit very large molecular tilt fluctuations with magnitudes of up to 35
      degrees --thus larger than the average tilt itself. This is essential to
      understand the underlying molecular mechanism behind the practical absence of
      smectic layer contraction in these materials: in the SmA phase, the nematic order
      parameter is very low (molecular fluctuations correspondingly high), and the
      expected layer shrinkage at the SmA to SmC transition is almost fully compensated
      by the increase in orientational order, as the fluctuations diminish with
      decreasing temperature. In addition to the general tilt fluctuations, we observe
      intrinsic soft-mode fluctuations. They have a lambda-shaped temperature
      dependence that peaks at the SmA-SmC transition with a maximum amplitude of about
      2 degrees .

PMID- 23877995
TI  - Multidose drug dispensing and optimising drug use in older people.

PMID- 23877996
TI  - Beyond the nasoseptal flap: outcomes and pearls with secondary flaps in
      endoscopic endonasal skull base reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: Endoscopic endonasal skull base surgery defects require
      effective reconstruction. Although the nasoseptal flap (NSF) has become our
      institution's workhorse for large skull base defects with cerebrospinal fluid
      (CSF) leaks, situations where it is unavailable require secondary flaps. Clinical
      outcomes, pearls and pitfalls, and an algorithm will be presented for these
      secondary flaps. STUDY DESIGN: Clinical case series. METHODS: Medical records of
      all endoscopic endonasal skull base surgeries at a tertiary care academic medical
      center were reviewed for skull base defect type, reconstruction method, CSF leak
      rate, and flap necrosis rate. RESULTS: Of 330 flaps for reconstructing endoscopic
      endonasal skull base defects, secondary flaps were used in 34 cases (10%). These
      included 16 endoscopic-assisted pericranial flaps, seven tunneled temporoparietal
      fascia flaps, three inferior turbinate flaps, two middle turbinate flaps, two
      anterior lateral nasal wall flaps, two palatal flaps, one occipital flap, and one
      facial artery buccinator flap. There were 19 anterior cranial fossa defects, 10
      clival defects, three sellar defects, and one frontal and one lateral
      orbit/middle fossa defect. Twenty-five of the 34 cases (73.5%) had either prior
      or postoperative radiation therapy. The most common pathology was sinonasal
      cancer, with 16 cases (47.1%). The postoperative CSF leak rate was 3.6% due to
      one middle turbinate flap necrosis. CONCLUSIONS: Secondary flaps for skull base
      reconstruction can be harvested with minimally invasive techniques and
      demonstrate excellent success rates (97%) that are comparable to that of the NSF
      (>95%). Multiple flaps for complex skull base defects should be in the
      armamentarium of comprehensive skull base surgery centers. LEVEL OF EVIDENCE: 4.

PMID- 23877997
TI  - Local administration of alendronate reduced peri-tunnel bone loss and promoted
      graft-bone tunnel healing with minimal systemic effect on bone in contralateral
      knee.
AB  - Continued systemic administration of alendronate was reported to reduce peri
      tunnel bone resorption and promoted graft-bone tunnel healing at the early stage
      post-anterior cruciate ligament (ACL) reconstruction. However, systemic increase
      in bone mineral density (BMD) in the contralateral intact knee was observed. We
      tested if single local administration of alendronate into the bone tunnel during
      ACL reconstruction could achieve similar benefits yet without the systemic effect
      on bone. Seventy-two rats with unilateral ACL reconstruction were divided into
      three groups: saline, low-dose (6 MUg/kg) and mid-dose (60 MUg/kg) alendronate.
      For local administration, alendronate was applied to the bone tunnels for 2 min
      before graft insertion and repair. At weeks 2 and 6, the reconstructed complex
      was harvested for high-resolution computed tomography (vivaCT) imaging followed
      by biomechanical test or histology. Our results showed that local administration
      of low-dose alendronate showed comparable benefits on the reduction of peri
      tunnel bone loss, enhancement of bone tunnel mineralization, tunnel graft
      integrity, graft osteointegration and mechanical strength of the reconstructed
      complex at early stage post-reconstruction, yet with minimal systemic effect on
      mineralized tissue at the contralateral intact knee. A single local
      administration of alendronate at the low-dose therefore might be used to promote
      early tunnel graft healing post-reconstruction.

PMID- 23877998
TI  - A new tridentate sulfur receptor as a highly sensitive and selective fluorescent
      sensor for Cu2+ ions.
AB  - The introduction of Lawesson's reagent into a bis-rhodamine spirolactam system
      afforded a new fluorescent sensor for Cu(2+) ions, SRR, which contained a new
      tridentate sulfur ligand. SRR showed excellent specificity for Cu(2+) ions over
      other cations (including Cu(+), Hg(2+), and Fe(3+)), very high sensitivity (10
      nM), and a rapid response time (3 min). The detection mechanism was investigated
      by (1)H NMR, (13)C NMR, (31)P NMR, and ESR spectroscopy, MS, and Gaussian
      calculations. Coordination of a Cu(2+) ion to the tridentate sulfur ligand, which
      promotes ring-opening of the rhodamine groups, followed by a spontaneous
      reduction reaction (Cu(2+) into Cu(+)), has been proposed as the sensing
      mechanism.

PMID- 23877999
TI  - MicroRNAs as Neuronal Fate Determinants.
AB  - Since the discovery of short, regulatory microRNAs (miRNA) 20 years ago, the
      understanding of their impact on gene regulation has dramatically increased.
      Differentiation of cells requires comprehensive changes in regulatory networks at
      all levels of gene expression. Posttranscriptional regulation by miRNA leads to
      rapid modifications in the protein level of large gene networks, and it is
      therefore not surprising that miRNAs have been found to influence the fate of
      differentiating cells. Several recent studies have shown that overexpression of a
      single miRNA in different cellular contexts results in forced differentiation of
      nerve cells. Loss of this miRNA constrains neurogenesis and promotes gliogenesis.
      This miRNA, miR-124, is probably the most well-documented example of a miRNA that
      controls nerve cell fate determination. In this review we summarize the recent
      findings on miR-124, potential molecular mechanisms used by miR-124 to drive
      neuronal differentiation, and outline future directions. 

PMID- 23878000
TI  - Male mice express spermatogenic cell-specific triosephosphate isomerase isozymes.
AB  - Triosephosphate isomerase 1 (TPI1) is a member of the glycolytic pathway, which
      is a critical source of energy for motility in mouse sperm. By immunoblotting, we
      detected two male, germ line-specific TPI1 bands (Mr 33,400 and 30,800) as well
      as the somatic-type band (Mr 27,700). Although all three bands were observed in
      spermatogenic cells, somatic-type TPI1 disappeared from sperm during epididymal
      maturation. In vitro dephosphorylation analysis suggested that the two male, germ
      line-specific TPI1 bands were not the result of phosphorylation of the 27,700 Mr
      TPI1 band. The Mr 33,400; 30,800; and 27,700 TPI1 bands corresponded to the
      respective sizes of the proteins predicted to use the first, second, and third
      possible initiation codons of the Tpi1 cDNA. We performed immunofluorescence on
      epididymal sperm and determined that TPI1 specifically localized in the principal
      piece. The antibody staining was stronger in cauda epididymal sperm than in caput
      epididymal sperm, a finding consistent with the identification of TPI1 as a cauda
      epididymal sperm-enriched protein. Immunofluorescence with sodium dodecyl sulfate
      (SDS)-insoluble flagellar accessory structures showed a strong TPI1 signal only
      in the principal piece, indicating that TPI1 is a component of the fibrous
      sheath. Northern blot hybridization detected longer Tpi1 transcripts (1.56 kb) in
      mouse testis, whereas somatic tissues had shorter transcripts (1.32 kb). As there
      is only one triosephosphate isomerase gene in the mouse genome, we conclude that
      the three variants we see in sperm result from the use of alternative translation
      start codons in spermatogenic cells.

PMID- 23878001
TI  - Ultrafast NMR T1 relaxation measurements: probing molecular properties in real
      time.
AB  - The longitudinal relaxation properties of NMR active nuclei carry useful
      information about the site-specific chemical environments and about the mobility
      of molecular fragments. Molecular mobility is in turn a key parameter reporting
      both on stable properties, such as size, as well as on dynamic ones, such as
      transient interactions and irreversible aggregation. In order to fully
      investigate the latter, a fast sampling of the relaxation parameters of
      transiently formed molecular species may be needed. Nevertheless, the acquisition
      of longitudinal relaxation data is typically slow, being limited by the
      requirement that the time for which the nucleus relaxes be varied incrementally
      until a complete build-up curve is generated. Recently, a number of single-shot
      inversion-recovery methods have been developed capable of alleviating this need;
      still, these may be challenged by either spectral resolution restrictions or when
      coping with very fast relaxing nuclei. Here, we present a new experiment to
      measure the T1s of multiple nuclear spins that experience fast longitudinal
      relaxation, while retaining full high-resolution chemical shift information. Good
      agreement is observed between T1s measured with conventional means and T1s
      measured using the new technique. The method is applied to the real-time
      investigation of the reaction between D-xylose and sodium borate, which is in
      turn elucidated with the aid of ancillary ultrafast and conventional 2D TOCSY
      measurements.

PMID- 23878002
TI  - Tumor-induced myeloid-derived suppressor cell subsets exert either inhibitory or
      stimulatory effects on distinct CD8+ T-cell activation events.
AB  - Tumor growth coincides with an accumulation of myeloid-derived suppressor cells
      (MDSCs), which exert immune suppression and which consist of two main
      subpopulations, known as monocytic (MO) CD11b(+) CD115(+) Ly6G(-) Ly6C(high)
      MDSCs and granulocytic CD11b(+) CD115(-) Ly6G(+) Ly6C(int) polymorphonuclear
      (PMN)-MDSCs. However, whether these distinct MDSC subsets hamper all aspects of
      early CD8(+) T-cell activation--including cytokine production, surface marker
      expression, survival, and cytotoxicity--is currently unclear. Here, employing an
      in vitro coculture system, we demonstrate that splenic MDSC subsets suppress
      antigen-driven CD8(+) T-cell proliferation, but differ in their dependency on IFN
      gamma, STAT-1, IRF-1, and NO to do so. Moreover, MO-MDSC and PMN-MDSCs diminish
      IL-2 levels, but only MO-MDSCs affect IL-2Ralpha (CD25) expression and STAT-5
      signaling. Unexpectedly, however, both MDSC populations stimulate IFN-gamma
      production by CD8(+) T cells on a per cell basis, illustrating that some T-cell
      activation characteristics are actually stimulated by MDSCs. Conversely, MO-MDSCs
      counteract the activation-induced change in CD44, CD62L, CD162, and granzyme B
      expression, while promoting CD69 and Fas upregulation. Together, these effects
      result in an altered CD8(+) T-cell adhesiveness to the extracellular matrix and
      selectins, sensitivity to FasL-mediated apoptosis, and cytotoxicity. Hence, MDSCs
      intricately influence different CD8(+) T-cell activation events in vitro, whereby
      some parameters are suppressed while others are stimulated.

PMID- 23878003
TI  - Stenting of the eustachian tube to prevent otitis media with effusion after
      maxillary swing approach nasopharyngectomy.
AB  - OBJECTIVES/HYPOTHESIS: Our previous report recommended that the management of
      ipsilateral otitis media with effusion (OME) after maxillary swing
      nasopharyngectomy was observation. The idea of introducing a stent into the
      eustachian tube (ET) at the nasopharyngeal side after nasopharyngectomy may
      prevent postoperative OME. The purpose of this study was to examine the
      feasibility of intraoperative ET stenting and the efficacy of preventing
      ipsilateral OME formation. STUDY DESIGN: Prospective cohort study. METHODS: From
      2009 to 2011, 28 patients with nasopharyngectomy via the maxillary swing approach
      were recruited. Patients with curative resection were recruited (n = 21). ET
      stenting was performed intraoperatively using a 16-gauge Angiocath (BD Medical
      Systems, Franklin Lakes, NJ) with dimensions of 1.7 mm * 30 mm. The stent stays
      inplace indefinitely. The otologic status was evaluated using otoscopy, pure-tone
      audiogram, and tympanogram at 3 months, 6 months, and 1 year after the surgery.
      The outcomes were analyzed and compared with historical control. RESULTS: There
      were 9 (43%) patients with no OME at 6 months after surgery, and 15 (71%)
      patients had no OME at 1 year postoperatively. The results were statistically
      significant (P < .0001) when compared with our historical control of no ET
      stenting. There was no incidence of adverse effects of the stenting, such as
      acute otitis media, dislodgement of the stent, otalgia, and nasal pain.
      CONCLUSIONS: ET stenting was feasible after nasopharyngectomy. ET stenting
      prevented a significant number of patients from suffering from ipsilateral OME
      and alleviated the symptoms of unilateral aural fullness and unilateral
      conductive hearing impairment up to at least 1 year after the surgery. ET
      stenting is recommended in all patients after maxillary swing nasopharyngectomy.

PMID- 23878004
TI  - Hyperbaric oxygen therapy suppresses osteoclast formation and bone resorption.
AB  - The cellular and molecular mechanism through which hyperbaric oxygen therapy
      (HBO) improves osteonecrosis (ON) is unclear. The present study therefore
      examined the effect of HBO, pressure and hyperoxia on RANKL-induced osteoclast
      formation in RAW 264.7 cells and human peripheral blood monocytes (PBMC). Daily
      exposure to HBO (2.4 ATA, 97% O2 , 90 min), hyperbaric pressure (2.4 ATA, 8.8% O2
      , 90 min) or normobaric hyperoxia (1 ATA, 95% O2 , 90 min) significantly
      decreased RANKL-induced osteoclast formation and bone resorption in normoxic
      conditions. HBO had a more pronounced anti-osteoclastic effect than hyperoxia or
      pressure alone and also directly inhibited osteoclast formation and resorption in
      hypoxic conditions a hallmark of many osteolytic skeletal disorders. The
      suppressive action of HBO was at least in part mediated through a reduction in
      RANK, NFATc1, and Dc-STAMP expression and inhibition of hypoxia-induced HIF
      1alpha mRNA and protein expression. This data provides mechanistic evidence
      supporting the use of HBO as an adjunctive therapy to prevent osteoclast
      formation and bone loss associated with low oxygen partial pressure.

PMID- 23878006
TI  - Substituent and solvent effects on the electrochemical properties and
      intervalence transfer in asymmetric mixed-valent complexes consisting of
      cyclometalated ruthenium and ferrocene.
AB  - Four heterodimetallic complexes [Ru(Fcdpb)(L)](PF6) (Fcdpb=2-deprotonated form of
      1,3-di(2-pyridyl)-5-ferrocenylbenzene; L=2,6-bis-(N-methylbenzimidazolyl)
      pyridine (Mebip), 2,2':6',2''-terpyridine (tpy), 4-nitro-2,2':6',2''-terpyridine
      (NO2tpy), and trimethyl-4,4',4''-tricarboxylate-2,2':6',2''-terpyridine
      (Me3tctpy)) have been prepared. The electrochemical and spectroelectrochemical
      properties of these complexes have been examined in CH2Cl2, CH3NO2, CH3CN, and
      acetone. These complexes display two consecutive redox couples owing to the
      stepwise oxidation of the ferrocene (Fc) and ruthenium units, respectively. The
      potential difference, DeltaE(1/2)(E(1/2)(Ru(II/III))-E(1/2)(Fc(0/+))), decreased
      slightly with increasing solvent donocity. The mixed-valent states of these
      complexes have been generated by electrolysis and the resulting intervalence
      charge-transfer (IVCT) bands have been analyzed by Hush theory. Good linear
      relationships exist between the energy of the IVCT band, E(op), and DeltaE(1/2)
      of four mixed-valent complexes in a given solvent.

PMID- 23878005
TI  - Magnesium sulfate potentiates effect of DigiFab on marinobufagenin-induced Na/K
      ATPase inhibition.
AB  - BACKGROUND: Immunoneutralization of elevated circulating levels of endogenous
      digitalis-like Na/K-ATPase inhibitors (i.e. cardiotonic steroids (CTS))
      represents a novel approach in the treatment of preeclampsia (PE). Recently we
      demonstrated that DigiFab (Fab fragments of affinity-purified ovine digoxin
      antibody) restores PE-induced inhibition of Na/K-ATPase in erythrocytes ex vivo.
      Previously magnesium ions were shown to antagonize digitalis-induced toxicity,
      which is mediated by Na/K-ATPase inhibition. We hypothesized that magnesium
      sulfate would potentiate the effect of DigiFab in the reversal of CTS-induced
      Na/K-ATPase inhibition. METHODS: To test this hypothesis, we studied the ex vivo
      effect of DigiFab on Na/K-ATPase activity in erythrocytes from patients with PE
      in the absence and in the presence of 3 mmol/L magnesium sulfate. RESULTS:
      Compared with 11 normotensive pregnant subjects (29 +/- 1 years; gestational age
      = 39.0 +/- 0.2 weeks; blood pressure = 111 +/- 2/73 +/- 2 mm Hg), the 12 patients
      with PE (30 +/- 1 years; gestational age = 37.9 +/- 0.3 weeks; blood pressure =
      159 +/- 5/99 +/- 3 mm Hg) had plasma levels of marino-bufagenin increased 3-fold
      (1.38 +/- 0.40 vs. 0.38 +/- 0.10 nmol/L; P < 0.01) and activity of Na/K-ATPase in
      erythrocytes was inhibited (1.16 +/- 0.11 vs. 2.80 +/- 0.20 MUmol Pi/ml/h; P <
      0.01). Ex vivo, DigiFab (1 ug/ml) restored erythrocyte Na/K-ATPase activity (1.72
      +/- 0.13 umol Pi/ml/h; P < 0.01), and 3 mmol magnesium sulfate potentiated the
      effect of DigiFab (2.30 +/- 0.20 umol Pi/ml/h; P < 0.01). CONCLUSIONS: Magnesium
      is capable of increasing the efficacy of immunoneutralization of marinobufagenin
      induced Na/K-ATPase inhibition.

PMID- 23878007
TI  - Nasal tip support: a finite element analysis of the role of the caudal septum
      during tip depression.
AB  - OBJECTIVES/HYPOTHESIS: Although minor and major tip support mechanisms have been
      described in detail, no quantitative models exist to provide support for the
      relative contributions of the structural properties of the major alar cartilage,
      the fibrous attachments to surrounding structures, and the rigid support
      structures in an objective manner. STUDY DESIGN: The finite element method was
      used to compute the stress distribution in the nose during simple tip
      compression, and then identify the specific anatomic structures that resist
      deformation and thus contribute to tip support. Additionally, the impact of
      caudal septal resection on nasal tip support was examined. METHODS: The computer
      models consisted of three tissue components with anatomically correct geometries
      for skin and bone derived from computed tomographic data. Septum, upper lateral
      cartilages, and major alar cartilages were fitted within the model using three
      dimensional computer-aided design software. Five-millimeter nasal tip compression
      was performed on the models with caudal septal resection (3 and 5 mm) and without
      resection to simulate palpation, then the resulting spatial distribution of
      stress and displacement was calculated. RESULTS: The von Mises stress in the
      normal model was primarily concentrated along the medial crural angle. As caudal
      septum length was reduced, stress was redistributed to adjacent soft tissue and
      bone, resulting in less force acting on the septum. In all models, displacement
      was greatest near the intermediate crura. CONCLUSIONS: These models are the first
      step in the comprehensive mechanical analysis of nasal tip dynamics. Our model
      supports the concept of the caudal septum and major alar cartilage providing the
      majority of critical load-bearing support.

PMID- 23878008
TI  - Highly polarized Th17 cells induce EAE via a T-bet independent mechanism.
AB  - In the MOG35-55 induced EAE model, autoreactive Th17 cells that accumulate in the
      central nervous system acquire Th1 characteristics via a T-bet dependent
      mechanism. It remains to be determined whether Th17 plasticity and
      encephalitogenicity are causally related to each other. Here, we show that IL-23
      polarized T-bet(-/-) Th17 cells are unimpaired in either activation or
      proliferation, and induce higher quantities of the chemokines RANTES and CXCL2
      than WT Th17 cells. Unlike their WT counterparts, T-bet(-/-) Th17 cells retain an
      IL-17(hi) IFN-gamma(neg-lo) cytokine profile following adoptive transfer into
      syngeneic hosts. This population of highly polarized Th17 effectors is capable of
      mediating EAE, albeit with a milder clinical course. It has previously been
      reported that the signature Th1 and Th17 effector cytokines, IFN-gamma and IL-17,
      are dispensable for the development of autoimmune demyelinating disease. The
      current study demonstrates that the "master regulator" transcription factor, T
      bet, is also not universally required for encephalitogenicity. Our results
      contribute to a growing body of data showing heterogeneity of myelin-reactive T
      cells and the independent mechanisms they employ to inflict damage to central
      nervous system tissues, complicating the search for therapeutic targets relevant
      across the spectrum of individuals with multiple sclerosis. 

PMID- 23878009
TI  - Implant-associated localized osteitis in murine femur fracture by biofilm forming
      Staphylococcus aureus: a novel experimental model.
AB  - Staphylococcus aureus (SA) is the most common causative agent for implant
      associated osteitis. The present study characterizes a novel model of a low grade
      acute SA osteitis with bone defect in the femur which is stabilized by a titanium
      locking plate. Wild-type Balb/c mice were osteotomized, fixed by a locking plate
      and infected with SA. Mice underwent debridement 7 and 14 days later and were
      sacrificed at Day 28. At Days 7, 14, and 28 after inoculation local and systemic
      cell populations and IL-6 were analyzed. Fracture healing was quantified by
      radiography. The control group underwent the same procedure without infection.
      The bacterial load of implant-associated osteitis with biofilm formation was
      quantified by counting CFU and real-time PCR. Fracture healing determined by
      radiography was delayed in infected compared to non-infected mice. Throughout the
      investigation period CFU and leukocyte counts, as well as IL-6 levels were found
      to be significantly elevated in infected mice at the infection site but not
      systemically. Our murine model allows the detailed investigation of implant
      associated localized osteitis with biofilm producing SA and its influence on
      fracture healing. The model provides a tool to analyze therapeutic or
      prophylactic approaches to the problem of biofilm-associated osteitis.

PMID- 23878010
TI  - Supramolecular host-inhibited excited-state proton transfer and fluorescence
      switching of the anti-cancer drug, topotecan.
AB  - The effect of cucurbit[7]uril (CB[7]) nano-caging on the photophysical
      properties, particularly excited-state proton transfer (ESPT) reaction, of an
      eminent anti-cancer drug, topotecan (TPT), is demonstrated through steady-state
      and time-resolved fluorescence measurements. TPT in water (pH 6) exists
      exclusively as the cationic form (C) in the ground state. However, the drug
      emission mainly comes from the excited-state zwitterionic form (Z*) of TPT, and
      is attributed to water-assisted ESPT between the 10-hydroxyl group and water,
      which leads to the transformation of C* to Z* of TPT. In the presence of CB[7],
      it is found that selective encapsulation of the C form of TPT results in the
      formation of a 1:1 inclusion complex (CB[7]:TPT), and the ESPT process is
      inhibited by this encapsulation process. As a result, C* becomes the dominant
      emitting species in the presence of CB[7] rather than Z*, and fluorescence
      switching takes place from green to blue. Time-resolved studies also support the
      existence of CB[7]-encapsulated cationic species as the major emitting species in
      the presence of the macrocyclic host. Semi-empirical quantum chemical
      calculations are employed to gain insight into the molecular picture of
      orientation of TPT in the inclusion complex. It is clearly seen from the
      optimised structure of 1:1 CB[7]:TPT inclusion complex that both 10-hydroxyl and
      9-dimethylaminomethylene groups of TPT lie partly inside the cavity, and thereby
      inhibit the excited-state transformation of C* to Z* by the ESPT process.
      Finally, controlled release of the drug is achieved by means of fluorescence
      switching by introducing NaCl, which is rich in cells, as an external stimulus. 

PMID- 23878011
TI  - Effects of intraoperative external head cooling on short-term cognitive function
      in patients after coronary artery bypass graft surgery.
AB  - The aim of study was to assess the effects of an intraoperative external head
      cooling technique on cognitive dysfunction in the early postoperative period (at
      the 10th day) in patients after coronary artery bypass graft (CABG) surgery.
      Patients in Group H (n=25) were cooled with CPB and the intraoperative, external
      head-cooling technique, patients in Group C (n=25) were cooled only with
      cardiopulmonary bypass (CPB) to achieve mild hypothermia (33 - 34  degrees C).
      Cognitive function was analyzed before the operation and after the surgery using
      the Mini Mental State Examination (MMSE), the Modified Visual Reproduction Test
      from the Wechsler Memory Scale, Trail Making (A/B), WAIS--Digit Span (WDS) and
      WAIS Digit Symbol Substitution Test (WDSST). The incidence of cognitive
      impairment at the 10th day after the surgery was 36% (n=9) in Group H and 64%
      (n=16) in Group C (p=0.048). The temperature during the aortic cross-clamp period
      was associated with a lower rate of cognitive dysfunction (p=0.05, r(2)=0.09).
      The intraoperative, external head-cooling technique during the aortic cross-clamp
      period has a neuroprotective effect and leads to less short-term cognitive
      function impairment after CABG surgery.

PMID- 23878012
TI  - Hippocampal long-term depression in freely behaving mice requires the activation
      of beta-adrenergic receptors.
AB  - In the intact mouse hippocampus patterned afferent stimulation does not lead to
      long-term depression (LTD) at Schaffer collateral (Sc)-CA1 synapses, but the same
      synapses express robust LTD (<24 h) if test-pulse or patterned afferent
      experience is coupled with novel spatial learning. This suggests that the failure
      of sole afferent stimulation to elicit LTD relates to the absence of
      neuromodulatory input related to increased arousal or novelty during learning.
      Locus coeruleus (LC) firing increases during novel experience, and in rats
      patterned stimulation of the LC together with test-pulse stimulation of Sc-CA1
      synapses leads to robust LTD in vivo. This effect is mediated by beta-adrenergic
      receptors. Here, we explored if activation of beta-adrenergic receptors supports
      the expression of LTD in freely behaving mice. We also explored if beta
      adrenergic receptors contribute to endogenous LTD that is expressed following
      spatial learning. Patterned stimulation of Sc-CA1 synapses at 3 Hz (200 pulses)
      resulted in short-term depression (STD). Pretreatment with isoproterenol, an
      agonist of beta-adrenergic receptors, resulted in robust LTD (<24 h). Test-pulse
      stimulation under control conditions elicited field potentials that were stable
      for the 24-h monitoring period. Coupling of test-pulses with a novel spatial
      object recognition task resulted in robust endogenous LTD (<24 h). Pretreatment
      with propranolol, a beta-adrenergic receptor antagonist, completely prevented
      endogenous LTD that was enabled by learning and prevented object recognition
      learning itself. These data indicate that the absence of LTD in freely behaving
      mice, under standard recording conditions, does not reflect an inability of mice
      to express LTD, rather it is due to the absence of a noradrenalin tonus. Our data
      also support that spatial object recognition requires beta-adrenergic receptor
      activation. Furthermore, LTD that is enabled by novel spatial learning critically
      depends on activation of beta-adrenergic receptors that are presumably activated
      by noradrenalin released by the LC in response to the novel experience.

PMID- 23878013
TI  - Multivariable confounding adjustment in distributed data networks without sharing
      of patient-level data.
AB  - PURPOSE: It is increasingly necessary to analyze data from multiple sources when
      conducting public health safety surveillance or comparative effectiveness
      research. However, security, privacy, proprietary, and legal concerns often
      reduce data holders' willingness to share highly granular information. We
      describe and compare two approaches that do not require sharing of patient-level
      information to adjust for confounding in multi-site studies. METHODS: We
      estimated the risks of angioedema associated with angiotensin-converting enzyme
      inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and aliskiren in
      comparison with beta-blockers within Mini-Sentinel, which has created a
      distributed data system of 18 health plans. To obtain the adjusted hazard ratios
      (HRs) and 95% confidence intervals (CIs), we performed (i) a propensity score
      stratified case-centered logistic regression analysis, a method identical to a
      stratified Cox regression analysis but needing only aggregated risk set data, and
      (ii) an inverse variance-weighted meta-analysis, which requires only the site
      specific HR and variance. We also performed simulations to further compare the
      two methods. RESULTS: Compared with beta-blockers, the adjusted HR was 3.04 (95%
      CI: 2.81, 3.27) for ACEIs, 1.16 (1.00, 1.34) for ARBs, and 2.85 (1.34, 6.04) for
      aliskiren in the case-centered analysis. The corresponding HRs were 2.98 (2.76,
      3.21), 1.15 (1.00, 1.33), and 2.86 (1.35, 6.04) in the meta-analysis. Simulations
      suggested that the two methods may produce different results under certain
      analytic scenarios. CONCLUSION: The case-centered analysis and the meta-analysis
      produced similar results without the need to share patient-level data across
      sites in our empirical study, but may provide different results in other study
      settings.

PMID- 23878014
TI  - Including a range of outcome targets offers a broader view of fibromyalgia
      treatment outcome: results from a retrospective review of multidisciplinary
      treatment.
AB  - BACKGROUND: Fibromyalgia is associated with substantial functional disability.
      Current drug and non-drug treatments result in statistically significant but
      numerically small improvements in typical numeric measures of pain severity and
      fibromyalgia impact. OBJECTIVE: The aim of the present study was to evaluate
      additional measures of pain severity and functional outcome that might be
      affected by fibromyalgia treatment. METHODS: This retrospective review evaluated
      outcomes from 274 adults with fibromyalgia who participated in a six-week,
      multidisciplinary treatment programme. Pain and function were evaluated on the
      first and final treatment visit. Pain was evaluated using an 11-point numerical
      scale to determine clinically meaningful pain reduction (decrease >= 2 points)
      and from a pain drawing. Function was evaluated by measuring active range of
      motion (ROM), walking distance and speed, upper extremity exercise repetitions,
      and self-reports of daily activities. RESULTS: Numerical rating scores for pain
      decreased by 10-13% (p < 0.01) and Fibromyalgia Impact Questionnaire (FIQ) scores
      decreased by 20% (p < 0.001). More substantial improvements were noted when using
      alternative measures. Clinically meaningful pain relief was achieved by 37% of
      patients, and the body area affected by pain decreased by 31%. ROM showed
      significant improvements in straight leg raise and cervical motion, without
      improvements in lumbar ROM. Daily walking distance increased fourfold and arm
      exercise repetitions doubled. CONCLUSION: Despite modest albeit statistically
      significant improvements in standard measures of pain severity and the FIQ, more
      substantial pain improvement was noted when utilizing alternative measures of
      pain and functional improvement. Alternative symptom assessment measures might be
      important outcome measures to include in drug and non-drug studies to better
      understand fibromyalgia treatment effectiveness.

PMID- 23878015
TI  - Corticosteroids directly reduce Staphylococcus aureus biofilm growth: an in vitro
      study.
AB  - OBJECTIVES/HYPOTHESIS: Clinical improvement in patients with chronic
      rhinosinusitis (CRS) treated with steroids alone has previously been ascribed to
      the steroids' anti-inflammatory properties rather than any direct effect on the
      bacteria. The aim of this study was to determine if commonly used intranasal
      steroids directly reduce bacterial biofilm production in vitro. STUDY DESIGN: In
      vitro comparative controlled trial. METHODS: Staphylococcus aureus biofilms were
      grown on minimum biofilm eradication concentration device pegs and treated with
      the commonly prescribed CRS topical steroids fluticasone, mometasone, or
      budesonide. These were dissolved in vehicle solvents and added to cerebrospinal
      fluid (CSF) broth. Concentrations (including therapeutic doses) tested for
      fluticasone and mometasone ranged from 25 MUg/200 MUL to 400 MUg/200 MUL, and
      from 16 MUg/200 MUL to 2000 MUg/200 MUL for budesonide. Control pegs were exposed
      to equivalent volumes of the appropriate solvent/CSF broth. Confocal scanning
      laser microscopy and COMSTAT software were used to quantify biofilms at 24 hours
      after treatment. RESULTS: Significant differences from control were found for
      fluticasone at 400 MUg/200 MUL (difference = -0.3065 MUm(3)/MUm(2), P = .007),
      mometasone at 300 MUg/200 MUL and 400 MUg/200 MUL (difference = -0.15
      MUm(3)/MUm(2), P = .006, and difference = -0.9193 MUm(3)/MUm(2), P = .034,
      respectively), and budesonide at 750 MUg/200 MUL, 1000 MUg/200 MUL and 2000
      MUg/200 MUL (difference = -1.0137 MUm(3)/MUm(2), P = .038, difference = -0.6164,
      P = .009, and difference = -0.1906 MUm(3)/MUm(2), P = .029, respectively).
      CONCLUSIONS: The concentrations of 400 MUg/200 MUL of fluticasone, 300 MUg and
      400 MUg/200 MUL of mometasone, and 750 MUg, 1,000 MUg, and 2,000 MUg/200 MUL of
      budesonide directly reduce biofilm production in vitro, outside of the
      inflammatory milieu.

PMID- 23878016
TI  - Neuron-specific enolase serum levels predict severe neuronal injury after
      extracorporeal life support in resuscitation.
AB  - OBJECTIVES: Extracorporeal life support (ECLS) is a rescue option in critically
      ill patients. Since fast available and appropriate for respiratory and
      circulatory failure, it is frequently applied in resuscitation scenarios.
      Neurological injury is a complication common in ECLS patients limiting outcome,
      particularly after resuscitation. In this study, the institutional ECLS database
      was used to correlate neuron-specific enolase (NSE) serum peak values with
      outcome of patients supported with venoarterial (VA) ECLS during cardiopulmonary
      resuscitation (CPR). METHODS: From January 2011 to August 2012, 31 patients were
      provided with a VA ECLS during CPR (external cardiac massage). Serum NSE peaks
      were monitored and correlated with neurological outcome and hospital mortality.
      Patients were divided into two groups with mild-to-moderate and high NSE levels
      (cut-off value 100 MUg/l). RESULTS: High NSE levels were seen in 7 patients (mean
      218 +/- 155 MUg/l) and mild-to-moderate levels in 24 patients (50 +/- 23 MUg/l, P
      = 0.0001). Duration of extracoporeal support was comparable in both groups (6.3
      +/- 7.5 vs 5.0 +/- 4.5 days, P = n.s.). Patients with mild-to-moderate NSE levels
      were significantly older than those with high NSE levels (58 +/- 16 vs 44 +/- 15
      years, P = 0.02). Six patients with high NSE levels (86%) developed severe
      neurological complications. Though 4 patients could be weaned from extracorporeal
      support, hospital mortality was 86% (6 patients). In contrast, patients with mild
      to-moderate NSE levels had a hospital mortality of 46% (11 patients). Eighteen
      patients (75%) could be weaned from the device, and incidence of major
      neurological events was 29% (6 patients) only. Serum pH and lactate levels before
      ECLS implantation were significantly lower in patients with mild-to-moderate NSE
      values (pH: 7.23 +/- 0.04 vs 6.93 +/- 0.12, P = 0.039; lactate: 106 +/- 11 vs 161
      +/- 16 mg/l, P = 0.023). CONCLUSIONS: High NSE serum levels after ECLS correspond
      to poor neurological outcome and considerable mortality. Therefore, early
      neuroimaging is reasonable for determining therapeutic strategies in patients
      with high NSE peaks after resuscitation and extracorporeal support.

PMID- 23878017
TI  - Isolated Roux-en-Y anastomosis of the pancreatic stump in a duct-to-mucosa
      fashion in patients with distal pancreatectomy with en-bloc celiac axis
      resection.
AB  - BACKGROUND: A pancreatic fistula is one of the most serious complications in
      distal pancreatectomy with en bloc celiac axis resection (DP-CAR), because the
      pancreatic transection is performed on the right side of the portal vein, which
      results in a large cross-section surface, and because post-pancreatectomy
      hemorrhage is hard to treat by interventional radiology. Therefore, a procedure
      to decrease the incidence of postoperative pancreatic fistula is urgently needed.
      METHODS: Twenty-six consecutive patients who underwent DP-CAR between April 2008
      and August 2012 were reviewed retrospectively. The first 13 consecutive patients
      underwent DP-CAR with no anastomosis, and the subsequent 13 consecutive patients
      were treated with Roux-en-Y pancreaticojejunostomy (PJ) in a duct-to-mucosa
      fashion. RESULTS: Extremely high amylase levels (>4000 IU/l) of all drainage
      fluid specimens on postoperative day (POD) 1, 3 and 4 were detected more
      frequently in cases with no anastomosis (n = 7) compared to those with PJ (n = 1)
      (P = 0.056). CONCLUSION: The incidence of grade B/C pancreatic fistulas was 15.4%
      in cases with isolated Roux-en-Y anastomosis of the pancreatic stump performed in
      a duct-to-mucosa fashion, and we are currently examining whether this anastomosis
      method reduces the pancreatic fistula rate in a multicenter, randomized
      controlled trial for distal pancreatectomy patients (ClinicalTrials.gov
      NCT01384617).

PMID- 23878018
TI  - Connexin 43 is a potential regulator in fluid shear stress-induced signal
      transduction in osteocytes.
AB  - Connexin 43 (Cx43), a gap junctional protein, regulates osteocyte viability, and
      modulates mechanical stimulation-induced bone remodeling. However, the underlying
      mechanisms of its action remain unclear. In the current study, osteocyte-like MLO
      Y4 cells were exposed to fluid shear stress (FSS) of 16 (physiological) or 30
      (high) dyne/cm(2) for the indicated time points. Cx43 gene (Gja1) was silenced
      using siRNA or the protein was blocked chemically. The signaling molecules
      related to osteocyte apoptosis, osteogenesis, or osteoclastogenesis were detected
      at mRNA or protein levels. The results showed that physiological FSS
      significantly upregulated Cx43, which further inhibited apoptosis pathways (e.g.,
      caspase-3) and osteoclastogenesis signaling (e.g., RANKL), but activated
      osteogenesis signaling (Sost/sclerostin). Suppressing Cx43 gene (Gja1) by siRNA
      or chemically blocking gap junction communication enhanced caspase-3, RANKL, and
      Sost/sclerostin, which could be restored with physiological FSS over 8 h. In
      addition, high FSS decreased Cx43 expression and adversely affected signaling
      molecules compared with physiological FSS. The findings indicate the involvement
      of Cx43 in mechanotransduction of FSS and in the modulation of mechanical loading
      related apoptosis, osteogenesis, and osteoclastogenesis of osteocytes. This may
      provide a cellular and molecular basis for interpreting the biomechanical
      mechanism of bone absorption and remodeling.

PMID- 23878020
TI  - Non-operative management of blunt liver injury: a new protocol for selected
      hemodynamically unstable patients under hypotensive resuscitation.
AB  - BACKGROUND: The objective of this study was to evaluate our new protocol for
      performing non-operative management for selected unstable patients under
      hypotensive resuscitation using improved diagnostic imaging techniques. METHODS:
      This retrospective study included 77 consecutive patients with blunt liver
      injury. They were divided into two groups: those treated before and those treated
      after the revision. Under the new protocol, we attempted to manage the patients
      non-operatively, usually with angioembolization, including those whose shock
      improved with fluid resuscitation and continuous loading, permitting the
      maintenance of a target systolic blood pressure of 80 mmHg. The outcomes of the
      two groups were evaluated and compared. RESULTS: While comparing the groups,
      although there was no change in the liver-related morbidity and mortality rates,
      the urgent and overall laparotomy rates and transfusion requirements in 24 h
      significantly decreased after the protocol revision. While comparing the
      subgroups of high-grade injury (AAST Grades 3-5), the overall laparotomy rates
      and transfusion requirements in 24 h significantly decreased after the protocol
      revision. CONCLUSIONS: All the selected unstable patients were successfully
      managed non-operatively after the protocol revision. The decrease in laparotomy
      rates and transfusion requirements confirmed the feasibility of our new protocol
      for these selected patients.

PMID- 23878019
TI  - T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune
      disease.
AB  - T cells that produce both IL-17 and IFN-gamma, and co-express ROR-gammat and T
      bet, are often found at sites of autoimmune inflammation. However, it is unknown
      whether this co-expression of T-bet with ROR-gammat is a prerequisite for
      immunopathology. We show here that T-bet is not required for the development of
      Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not
      impaired in T-bet(-/-) mice and was associated with low IFN-gamma production and
      elevated IL-17 production among central nervous system (CNS) infiltrating CD4(+)
      T cells. T-bet(-/-) Th17 cells generated in the presence of IL-6/TGF-beta/IL-1
      and IL-23 produced GM-CSF and high levels of IL-17 and induced disease upon
      transfer to naive mice. Unlike their WT counterparts, these T-bet(-/-) Th17 cells
      did not exhibit an IL-17->IFN-gamma switch upon reencounter with antigen in the
      CNS, indicating that this functional change is not critical to disease
      development. In contrast, T-bet was absolutely required for the pathogenicity of
      myelin-responsive Th1 cells. T-bet-deficient Th1 cells failed to accumulate in
      the CNS upon transfer, despite being able to produce GM-CSF. Therefore, T-bet is
      essential for establishing Th1-mediated inflammation but is not required to drive
      IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation. 

PMID- 23878021
TI  - Intentional harms are worse, even when they're not.
AB  - People and societies seek to combat harmful events. However, because resources
      are limited, every wrong righted leaves another wrong left unchecked. Responses
      must therefore be calibrated to the magnitude of the harm. One underappreciated
      factor that affects this calibration may be people's oversensitivity to intent.
      Across a series of studies, people saw intended harms as worse than unintended
      harms, even though the two harms were identical. This harm-magnification effect
      occurred for both subjective and monetary estimates of harm, and it remained when
      participants were given incentives to be accurate. The effect was fully mediated
      by blame motivation. People may therefore focus on intentional harms to the
      neglect of unintentional (but equally damaging) harms. 

PMID- 23878022
TI  - Designing and delivering an educational package to meet the needs of primary care
      health professionals in the diagnosis and management of those with complex
      regional pain syndrome.

PMID- 23878023
TI  - Quantitative (31)P HR-MAS MR spectroscopy for detection of response to PI3K/mTOR
      inhibition in breast cancer xenografts.
AB  - PURPOSE: Phospholipid metabolites are of importance in cancer studies, and have
      been suggested as candidate metabolic biomarkers for response to targeted
      anticancer drugs. The purpose of this study was to develop a phosphorus ((31) P)
      high resolution magic angle spinning magnetic resonance spectroscopy protocol for
      quantification of phosphorylated metabolites in intact cancer tissue. METHODS:
      (31) P spectra were acquired on a 14.1 T spectrometer with a triplet (1) H/(13)
      C/(31) P MAS probe. Quantification of metabolites was performed using the PULCON
      principle. Basal-like and luminal-like breast cancer xenografts were treated with
      the dual PI3K/mTOR inhibitor BEZ235, and the impact of treatment on the
      concentration of phosphocholine, glycerophosphocholine, phosphoethanolamine and
      glycerophosphoethanolamine was evaluated. RESULTS: In basal-like xenografts,
      BEZ235 treatment induced a significant decrease in phosphoethanolamine (-25.6%, P
      = 0.01) whilst phosphocholine (16.5%, P = 0.02) and glycerophosphocholine (37.3%,
      P < 0.001) were significantly increased. The metabolic changes could partially be
      explained by increased levels of phospholipase A2 group 4A (PLA2G4A). CONCLUSION:
      (31) P high resolution magic angle spinning magnetic resonance spectroscopy is a
      useful method for quantitative assessment of metabolic responses to PI3K
      inhibition. Using the PULCON principle for quantification, the levels of
      phosphocholine, glycerophosphocholine, phosphoethanolamine, and
      glycerophosphoethanolamine could be evaluated with high precision and accuracy.

PMID- 23878024
TI  - A modified grapefruit juice eliminates two compound classes as major mediators of
      the grapefruit juice-fexofenadine interaction: an in vitro-in vivo "connect".
AB  - The grapefruit juice (GFJ)-fexofenadine interaction involves inhibition of
      intestinal organic anion transporting polypeptide (OATP)-mediated uptake. Only
      naringin has been shown clinically to inhibit intestinal OATP; other constituents
      have not been evaluated. The effects of a modified GFJ devoid of furanocoumarins
      (~99%) and polymethoxyflavones (~90%) on fexofenadine disposition were compared
      to effects of the original juice. Extracts of both juices inhibited estrone 3
      sulfate and fexofenadine uptake by similar extents in OATP-transfected cells
      (~50% and ~25%, respectively). Healthy volunteers (n = 18) were administered
      fexofenadine (120 mg) with water, GFJ, or modified GFJ (240 mL) by randomized,
      three-way crossover design. Compared to water, both juices decreased fexofenadine
      geometric mean AUC and C(max) by ~25% (P <= .008 and P <= .011, respectively),
      with no effect on terminal half-life (P = .11). Similar effects by both juices on
      fexofenadine pharmacokinetics indicate furanocoumarins and polymethoxyflavones
      are not major mediators of the GFJ-fexofenadine interaction.

PMID- 23878026
TI  - Endarteritis complicating aortic dissection.

PMID- 23878025
TI  - NKp46 regulates allergic responses.
AB  - Natural killer (NK) cells are cytotoxic cells that are able to rapidly kill
      viruses, tumor cells, parasites, bacteria, and even cells considered "self". The
      activity of NK cells is controlled by a fine balance of inhibitory and activating
      signals mediated by a complex set of different receptors. However, the function
      of NK cells is not restricted only to the killing of target cells, NK cells also
      possess other properties such as the secretion of proangiogenic factors during
      pregnancy. Here, we demonstrate another unique NK-cell activity, namely the
      regulation of T-cell mediated allergic responses, which is dependent on the NK
      cell specific receptor NKp46 (Ncr1 in mice). Using mice in which the Ncr1 gene
      has been replaced with a green fluorescent protein, we demonstrate reduced
      delayed-type hypersensitivity and airway hypersensitivity. Interestingly, we show
      that this reduction in airway hypersensitivity is due to differences in the
      stimulation of T cells resulting in an altered cytokine profile. 

PMID- 23878028
TI  - AICT - APSIC official scientific meeting.

PMID- 23878027
TI  - Validation of quantitative bound- and pore-water imaging in cortical bone.
AB  - PURPOSE: To implement and validate a previously proposed ultra-short echo time
      method for measuring collagen-bound- and pore-water concentrations in bone based
      on their T2 differences. METHODS: Clinically compatible ultra-short echo time
      image sequences for quantitative T2 -based bound and pore-water imaging in bone
      were implemented and validated on a 3T human scanner and a 4.7T small bore
      system. Bound- and pore-water images were generating using T2 -selective
      adiabatic pulses. In both cases, the magnetization preparation was integrated
      into a three-dimensional ultra-short echo time acquisition, with 16 radial spokes
      acquired per preparation. Images were acquired from human cadaveric femoral mid
      shafts from which isolated bone samples were subsequently extracted for
      nonimaging analysis using T2 spectroscopic measurements. RESULTS: A strong
      correlation was found between imaging-derived concentrations of bound and pore
      water and those determined from the isolated bone samples. CONCLUSIONS: These
      studies demonstrate the translation of the previously developed approaches for
      distinguishing bound and pore water from human cortical bone using practical
      human MRI constraints of gradient performance and radiofrequency power
      deposition.

PMID- 23878029
TI  - Glycoprotein inhibitors: not dead yet.

PMID- 23878030
TI  - MASTER trial: In search of the optimal PCI approach to STEMI.

PMID- 23878031
TI  - ST-segment elevation myocardial infarction related to stent thrombosis and grafts
      vein thrombosis: separating apples from oranges.

PMID- 23878032
TI  - Is no-no-reflow following PCI in AMI due to distal embolization of plaque and
      thrombus?

PMID- 23878033
TI  - Risky business: when patient preferences seem irrational.

PMID- 23878034
TI  - The need for emergency preparedness in the Cardiac Cath Lab.

PMID- 23878035
TI  - A new renal stent in the denervation era.

PMID- 23878036
TI  - Non-pharmacologic stroke prevention in atrial fibrillation: an issue without
      closure.

PMID- 23878037
TI  - In transcatheter aortic valve replacement: to balloon or not to balloon, that is
      the question.

PMID- 23878038
TI  - Fixing that vexing paravalvar leak.

PMID- 23878039
TI  - Left atrial appendage closure: does "leak" matter?

PMID- 23878040
TI  - Routine screening for suicidal intention in patients with cancer.
AB  - OBJECTIVES: Suicide rates are elevated in individuals with cancer, although
      suicidal intention is not typically assessed in cancer centers. We evaluated in a
      large comprehensive cancer center the utility of an electronic Distress
      Assessment and Response Tool (DART), in which suicidal intention is assessed with
      a single item. METHODS: Patients attending cancer clinics completed DART as part
      of routine care. DART includes measures of physical symptoms, depression,
      anxiety, social difficulties, and practical concerns. Medical variables were
      obtained from the Princess Margaret Cancer Registry, the data warehouse of cancer
      patient statistics. A Generalized Estimating Equation (GEE) model was used to
      assess factors associated with suicidal intention. RESULTS: Between September
      2009 and March 2012, 4822/5461 patients (88.3%) who completed DART consented to
      the use of their data for research. Amongst the latter, 280 (5.9%) of the 4775
      patients who answered the question reported suicidal ideation, which was related
      to physical and psychological distress, and social difficulties (ps < 0.0001).
      Amongst those with ideation who responded to the intention question, 20/186
      (10.8%) reported suicidal intention. Of respondents with more severe suicidal
      ideation, 12/49 (24.5%) reported suicidal intention. Using a GEE model, suicidal
      intention in those with ideation was significantly associated with male sex,
      difficulty making treatment decisions, and with everyday living concerns.
      CONCLUSIONS: Suicidal ideation is reported on an electronic distress screening
      tool (DART) by almost 6% of cancer patients, of whom almost 11% report suicidal
      intention and 33% decline to indicate intention. DART demonstrated utility in
      identifying patients who may be at highest risk of completed suicide and who
      require urgent clinical assessment.

PMID- 23878041
TI  - General movements in very preterm children and neurodevelopment at 2 and 4 years.
AB  - OBJECTIVE: Although ~50% of very preterm (VP) children have neurodevelopmental
      impairments, early prediction of infants who will experience problems later in
      life remains a challenge. This study evaluated the predictive value of general
      movements (GM; spontaneous and endogenous movements) at 1 and 3 months' corrected
      age for neurodevelopment at 2 and 4 years of age in VP children. METHODS: At 1
      and 3 months' corrected age, infants born <30 weeks' gestation had GM assessed as
      normal or abnormal. Motor, cognitive, and language development at 2 years was
      assessed by using the Bayley Scales of Infant and Toddler Development, Third
      Edition. At 4 years, cognitive and language outcomes were assessed by using the
      Differential Ability Scale-Second Edition and motor outcomes with the Movement
      Assessment Battery for Children-Second Edition; a diagnosis of cerebral palsy was
      documented. RESULTS: Ninety-nine VP infants were recruited, with 97% and 88% of
      survivors followed up at age 2 and 4 years, respectively. Abnormal GM at 1 month
      were associated with worse motor outcomes at 2 and 4 years but not language or
      cognitive outcomes. Abnormal GM at 3 months were associated with worse motor,
      cognitive, and language outcomes at both 2 and 4 years. Overall, GM at 1 month
      demonstrated better sensitivity to impairments at 2 and 4 years, whereas GM at 3
      months had better specificity and were more accurate overall at distinguishing
      between children with and without impairment. CONCLUSIONS: Abnormal GM in VP
      infants, particularly at 3 months postterm, are predictive of worse
      neurodevelopment at ages 2 and 4 years.

PMID- 23878042
TI  - Variation in pediatric care at US hospitals.

PMID- 23878043
TI  - Respiratory syncytial virus-associated hospitalizations among children less than
      24 months of age.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection is a leading cause of
      hospitalization among infants. However, estimates of the RSV hospitalization
      burden have varied, and precision has been limited by the use of age strata
      grouped in blocks of 6 to >= 12 months. METHODS: We analyzed data from a 5-year,
      prospective, population-based surveillance for young children who were
      hospitalized with laboratory-confirmed (reverse-transcriptase polymerase chain
      reaction) RSV acute respiratory illness (ARI) during October through March 2000
      2005. The total population at risk was stratified by month of age by birth
      certificate information to yield hospitalization rates. RESULTS: There were 559
      (26%) RSV-infected children among the 2149 enrolled children hospitalized with
      ARI (85% of all eligible children with ARI). The average RSV hospitalization rate
      was 5.2 per 1000 children <24 months old. The highest age-specific rate was in
      infants 1 month old (25.9 per 1000 children). Infants <= 2 months of age, who
      comprised 44% of RSV-hospitalized children, had a hospitalization rate of 17.9
      per 1000 children. Most children (79%) were previously healthy. Very preterm
      infants (<30 weeks' gestation) accounted for only 3% of RSV cases but had RSV
      hospitalization rates 3 times that of term infants. CONCLUSIONS: Young infants,
      especially those who were 1 month old, were at greatest risk of RSV
      hospitalization. Four-fifths of RSV-hospitalized infants were previously healthy.
      To substantially reduce the burden of RSV hospitalizations, effective general
      preventive strategies will be required for all young infants, not just those with
      risk factors.

PMID- 23878044
TI  - Variation in resource use and readmission for diabetic ketoacidosis in children's
      hospitals.
AB  - OBJECTIVE: We sought to characterize variation in hospital resource utilization
      and readmission for diabetic ketoacidosis (DKA) across US children's hospitals.
      METHODS: The study sample included a retrospective cohort of children aged 2 to
      18 years with a diagnosis of DKA at 38 children's hospitals between 2004 and
      2009. The main outcomes were resource utilization as determined by total
      standardized cost per hospitalization, overall and non-ICU length of stay (LOS),
      and readmission for DKA within 30 and 365 days. RESULTS: There were 24,890 DKA
      admissions, and 20.3% of these were readmissions within 1 year. The mean hospital
      level total standardized cost was $7142 (range $4125-$11,916). The mean hospital
      level LOS was 2.5 days (1.5-3.7), and the non-ICU portion was 1.9 days (0.7-2.7).
      The mean hospital-level readmission within 365 days was 18.7% (6.5%-41.1%) and
      within 30 days was 2.5% (0.0%-7.1%). Hospital bed days overall, and in particular
      the non-ICU portion, accounted for the majority of the total standardized cost
      per hospitalization (overall 57%; non-ICU 36%) and explained most of the
      variation in resource use. Even after adjusting for difference in patient
      characteristics across hospitals, widespread differences existed across hospitals
      in total standardized cost, LOS, and readmission rates (P < .001). CONCLUSIONS:
      Readmission for DKA within a year of hospitalization is common. US children's
      hospitals vary widely in resource use, hospital LOS, and readmission rates for
      patients with DKA. Our study highlights the need for additional research to
      understand these differences and to identify the most cost-effective strategies
      for managing diabetes across the continuum of care.

PMID- 23878045
TI  - Variation and trends in ED use of radiographs for asthma, bronchiolitis, and
      croup in children.
AB  - OBJECTIVES: The objectives were (1) to determine trends in radiograph use in
      emergency department (ED) care of children with asthma, bronchiolitis, and croup;
      and (2) to examine the association of patient and hospital factors with variation
      in radiograph use. METHODS: A retrospective, cross-sectional study of National
      Hospital Ambulatory Medical Care Survey data between 1995 and 2009 on radiograph
      use at ED visits in children aged 2 to 18 years with asthma, aged 3 months to 1
      year with bronchiolitis, and aged 3 months to 6 years with croup. Odds ratios
      (ORs) were calculated and adjusted for all factors studied. RESULTS: The use of
      radiographs for asthma increased significantly over time (OR: 1.06; 95%
      confidence interval [CI]: 1.03-1.09; P < .001 for trend) but were unchanged for
      bronchiolitis and croup. Pediatric-focused EDs had lower use for asthma (OR:
      0.44; 95% CI: 0.29-0.68), bronchiolitis (OR: 0.37; 95% CI: 0.23-0.59), and croup
      (OR: 0.34; 95% CI: 0.17-0.68). Compared with the Northeast region, the Midwest
      and South had statistically higher use of radiographs for all 3 conditions. The
      Western region had higher use only for asthma (OR: 1.67; 95% CI: 1.07-2.60), and
      bronchiolitis (OR: 2.94; 95% CI: 1.48-5.87). No associations were seen for
      metropolitan statistical area or hospital ownership status. CONCLUSIONS: The ED
      use of radiographs for children with asthma increased significantly from 1995 to
      2009. Reversing this trend could result in substantial cost savings and reduced
      radiation. Pediatric-focused EDs used significantly fewer radiographs for asthma,
      bronchiolitis, and croup. The translation of practices from pediatric-focused EDs
      to all EDs could improve performance.

PMID- 23878046
TI  - Use of ecallantide in pediatric hereditary angioedema.
AB  - OBJECTIVE: Hereditary angioedema (HAE) due to C1-inhibitor deficiency is a rare
      autosomal dominant disease that manifests as sudden unpredictable attacks of
      subcutaneous or submucosal edema affecting the skin, intestine, and upper airway.
      Ecallantide is a plasma kallikrein inhibitor indicated for treatment of HAE
      attacks in patients aged 16 years and older. This analysis examines safety and
      efficacy of ecallantide for treatment of HAE attacks in patients <18 years of
      age. METHODS: Data for patients aged 9 to 17 years treated subcutaneously with 30
      mg ecallantide or placebo were pooled from 4 clinical studies (2 double-blind,
      placebo-controlled and 2 open-label). Efficacy end points included 2 HAE-specific
      patient-reported outcome measures: mean symptom complex severity (MSCS) score and
      treatment outcome score (TOS). Times to initial improvement, sustained
      improvement, and complete or near-complete symptom resolution were calculated.
      Treatment-emergent adverse events were examined. RESULTS: Overall, 29 pediatric
      patients were included; 25 of them received ecallantide for 62 total HAE attacks,
      and 10 received placebo for 10 total attacks. Ecallantide-treated attacks
      revealed clinically relevant reduction in symptom severity at 4 hours postdosing
      based on mean change in MSCS score (-1.4 +/- 0.9 ecallantide versus -0.9 +/- 0.6
      placebo) and TOS (73.9 +/- 35.50 ecallantide versus 45.0 +/- 43.78 placebo).
      Patients treated with ecallantide showed rapid improvement in symptoms (median
      time to complete or near-complete symptom resolution: 181 minutes). No serious
      adverse events related to treatment were observed. CONCLUSIONS: Ecallantide
      appears effective for HAE attacks in adolescents, with rapid symptom improvement.
      No unexpected safety issues were identified.

PMID- 23878047
TI  - Television-related injuries to children in the United States, 1990-2011.
AB  - OBJECTIVE: To investigate the epidemiology of television (TV)-related injuries to
      children in the United States. METHODS: Using data from the National Electronic
      Injury Surveillance System, children aged <18 years treated in United States
      hospital emergency departments for an injury associated with a TV from 1990
      through 2011 were investigated. RESULTS: An estimated 380,885 patients aged <18
      years were treated in emergency departments for a TV-related injury during the 22
      year study period, which equals an annual average of 17,313 children. The median
      age of patients was 3 years; children <5 years represented 64.3% of patients, and
      boys comprised 60.8%. The average annual injury rate was 2.43 (95% confidence
      interval [CI]: 2.07-2.80) injuries per 10,000 children aged <18 years, with a
      range of 2.15 (95% CI: 1.64-2.66) to 2.90 (95% CI: 2.31-3.49). Although the
      overall injury rate was steady, the number and rate of injuries associated with
      falling TVs increased significantly by 125.5% and 95.3%, respectively, during the
      study period. In addition, there was a significant 344.1% increase in the number
      of injuries associated with a TV falling from a dresser/bureau/chest of
      drawers/armoire during 1995-2011. CONCLUSIONS: The rate of pediatric injuries
      caused by falling TVs is increasing, which underscores the need for increased
      prevention efforts. Prevention strategies include public education, provision of
      TV anchoring devices at the point of sale of TVs, TV anchoring device
      distribution programs, strengthening of standards for TV stability, and redesign
      of TVs to improve stability.

PMID- 23878048
TI  - Acute kernicterus in a neonate with O/B blood group incompatibility and a
      mutation in SLC4A1.
AB  - We cared for a term female newborn, who at 108 hours of age, with a total serum
      bilirubin of 15.4 mg/dL, was discharged from the hospital on home phototherapy.
      At a return appointment 44 hours later, her total serum bilirubin was 41.7 mg/dL
      and signs of acute kernicterus were present. Maternal/fetal blood group O/B
      incompatibility was identified, with a negative direct antiglobulin test, which
      was positive on retesting. She had abundant spherocytes on blood smear, and these
      persisted at follow-up, but neither parent had spherocytes identified. A
      heterozygous SLC4A1(E508K) mutation (gene encoding erythrocyte membrane protein
      band 3) was found, and in silico predicted to result in damaged erythrocyte
      cytoskeletal protein function. No mutations were identified in other red cell
      cytoskeleton genes (ANK1, SPTA1, SPTB, EPB41, EPB42) and the UGT1A1 promoter
      region was normal. Neurologic follow-up at 2 and 4 months showed developmental
      delays consistent with mild kernicterus. 

PMID- 23878049
TI  - Variation in emergency department diagnostic testing and disposition outcomes in
      pneumonia.
AB  - OBJECTIVE: To describe the variability across hospitals in diagnostic test
      utilization for children diagnosed with community-acquired pneumonia (CAP) during
      emergency department (ED) evaluation and to determine if test utilization is
      associated with hospitalization and ED revisits. METHODS: We conducted a
      retrospective cohort study of children aged 2 months to 18 years with ED visits
      resulting in CAP diagnoses from 2007 to 2010 who were seen at 36 hospitals
      contributing data to the Pediatric Health Information System. Children with
      complex chronic conditions, recent hospitalization, trauma, aspiration, or
      perinatal infection were excluded. Primary outcomes included diagnostic testing,
      hospitalization, and 3-day ED revisit rates across hospitals. We examined
      variation in diagnostic testing among hospitals by using multivariable mixed
      effects logistic regression. RESULTS: A total of 100,615 ED visits were analyzed.
      Complete blood count (median: 28.7%), blood culture (27.9%), and chest radiograph
      (75.7%) were the most commonly ordered ED diagnostic tests. After adjustment for
      patient characteristics, significant variation (P < .001) was found for each test
      examined across hospitals. High test-utilizing hospitals had increased odds of
      hospitalization compared with low-utilizing hospitals (odds ratio: 1.86 [95%
      confidence interval: 1.17-2.94]; P = .008). However, differences in the odds of
      ED revisit between the low- and high-utilizing hospitals were not significant
      (odds ratio: 1.21 [95% confidence interval: 0.97-1.51]; P = .09). CONCLUSIONS:
      Emergency departments that use more testing in diagnosing CAP have higher
      hospitalization rates than lower-utilizing EDs. However, ED revisit rates were
      not significantly different between high- and low-utilizing EDs. These results
      suggest an opportunity to reduce diagnostic testing for CAP without negatively
      affecting outcomes.

PMID- 23878050
TI  - The internet, adolescent males, and homemade blowgun darts: a recipe for foreign
      body aspiration.
AB  - We describe our experience with blowgun dart aspiration via an illustrative case
      series and review the resources available to teach children how to construct
      these objects. A 15-year-old boy presented with cough, wheeze, and eventually
      admitted to aspiration of a homemade blowgun dart. This instance heightened the
      awareness of our experience with blowgun dart aspiration as 3 cases presented
      within a 3-month period. Patients uniformly presented with cough and reported
      aspiration, and wheezing was noted in 2 of the 3. Although all ultimately
      admitted their behavior, 2 were initially reluctant to admit aspirating the
      blowgun dart. Radiographic findings of a needle-shaped metallic airway foreign
      body were consistent in all patients. Each admitted to finding instructions for
      blowgun dart construction on the Internet. Emergent rigid bronchoscopy with
      blowgun dart removal resulted in symptom resolution in all without complication.
      This represents the largest series of blowgun dart aspiration to date. During
      deep inhalation, when preparing to propel a blowgun dart, the vocal folds
      maximally abduct, leading to increased risk for aspiration. Twenty websites were
      identified providing instructions for the construction of homemade blowgun darts.
      With the accessibility of the Internet and number of instructional websites, this
      clinical entity may become more common in the future. Unfortunately, only a few
      of the websites provide any safety warnings. Certainly, prompt treatment can
      result in good outcomes; however, serious potential complications, including
      death, could occur especially given the hesitance our patients showed in
      divulging the truth of the inciting event. 

PMID- 23878051
TI  - Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants.
AB  - OBJECTIVE: To determine whether neonatal infections are associated with a higher
      risk of adverse neurodevelopment at 5 years of age in a population-based cohort
      of very preterm children. METHODS: We included all live births between 22 and 32
      weeks of gestation, from 9 regions in France, in 1997 (EPIPAGE study). Of the
      2665 live births, 2277 were eligible for a follow-up evaluation at 5 years of
      age: 1769 had a medical examination and 1495 underwent cognitive assessment.
      Cerebral palsy and cognitive impairment were studied as a function of early-onset
      sepsis (EOS) and late-onset sepsis (LOS), after adjustment for potential
      confounding factors, in multivariate logistic regression models. RESULTS: A total
      of 139 (5%) of the 2665 live births included in the study presented with EOS
      alone (without associated LOS), 752 (28%) had LOS alone (without associated EOS),
      and 64 (2%) displayed both EOS and LOS. At 5 years of age, the frequency of
      cerebral palsy was 9% (157 of 1769) and that of cognitive impairment was 12% (177
      of 1495). The frequency of cerebral palsy was higher in infants with isolated EOS
      (odds ratio [OR]: 1.70 [95% confidence interval (CI): 0.84-3.45]) or isolated LOS
      (OR: 1.71 [95% CI: 1.14-2.56]) than in uninfected infants, and this risk was even
      higher in cases of combined EOS and LOS (OR: 2.33 [95% CI: 1.02-5.33]). There was
      no association between neonatal infection and cognitive impairment. CONCLUSIONS:
      Neonatal infections in these very preterm infants were associated with a higher
      risk of cerebral palsy at the age of 5 years, particularly in infants presenting
      with both EOS and LOS.

PMID- 23878052
TI  - Patterns of retinal hemorrhage associated with increased intracranial pressure in
      children.
AB  - OBJECTIVE: Raised intracranial pressure (ICP) has been proposed as an isolated
      cause of retinal hemorrhages (RHs) in children with suspected traumatic head
      injury. We examined the incidence and patterns of RHs associated with increased
      ICP in children without trauma, measured by lumbar puncture (LP). METHODS:
      Children undergoing LP as part of their routine clinical care were studied
      prospectively at the Children's Hospital of Philadelphia and retrospectively at
      Nationwide Children's Hospital. Inclusion criteria were absence of trauma, LP
      opening pressure (OP) >= 20 cm of water (cm H2O), and a dilated fundus
      examination by an ophthalmologist or neuro-ophthalmologist. RESULTS: One hundred
      children were studied (mean age: 12 years; range: 3-17 years). Mean OP was 35 cm
      H2O (range: 20-56 cm H2O); 68 (68%) children had OP >28 cm H2O. The most frequent
      etiology was idiopathic intracranial hypertension (70%). Seventy-four children
      had papilledema. Sixteen children had RH: 8 had superficial intraretinal
      peripapillary RH adjacent to a swollen optic disc, and 8 had only splinter
      hemorrhages directly on a swollen disc. All had significantly elevated OP (mean:
      42 cm H2O). CONCLUSIONS: Only a small proportion of children with nontraumatic
      elevated ICP have RHs. When present, RHs are associated with markedly elevated
      OP, intraretinal, and invariably located adjacent to a swollen optic disc. This
      peripapillary pattern is distinct from the multilayered, widespread pattern of RH
      in abusive head trauma. When RHs are numerous, multilayered, or not near a
      swollen optic disc (eg, elsewhere in the posterior pole or in the retinal
      periphery), increased ICP alone is unlikely to be the cause.

PMID- 23878054
TI  - Low-voltage switching of crease patterns on hydrogel surfaces.
AB  - We report electrically driven creasing of polyelectrolye hydrogel surfaces with
      low switching voltages (2-4 V). Deep creases (up to 70% of the swelled film
      thickness) can be reversibly formed and eliminated on time-scales of a few
      seconds, with control of crease locations by micro-patterning of underlying
      electrodes. 

PMID- 23878055
TI  - Utilizing pharmacokinetics/pharmacodynamics modeling to simultaneously examine
      free CCL2, total CCL2 and carlumab (CNTO 888) concentration time data.
AB  - The chemokine ligand 2 (CCL2) promotes angiogenesis, tumor proliferation,
      migration, and metastasis. Carlumab is a human IgG1kappa monoclonal antibody with
      high CCL2 binding affinity. Pharmacokinetic/pharmacodynamic data from 21 cancer
      patients with refractory tumors were analyzed. The PK/PD model characterized the
      temporal relationships between serum concentrations of carlumab, free CCL2, and
      the carlumab-CCL2 complex. Dose-dependent increases in total CCL2 concentrations
      were observed and were consistent with shifting free CCL2. Free CCL2 declined
      rapidly after the initial carlumab infusion, returned to baseline within 7 days,
      and increased to levels greater than baseline following subsequent doses. Mean
      predicted half-lives of carlumab and carlumab-CCL2 complex were approximately 2.4
      days and approximately 1 hour for free CCL2. The mean dissociation constant (KD
      ), 2.4 nM, was substantially higher than predicted by in vitro experiments, and
      model-based simulation revealed this was the major factor hindering the
      suppression of free CCL2 at clinically viable doses. 

PMID- 23878053
TI  - Incidental findings in children with blunt head trauma evaluated with cranial CT
      scans.
AB  - OBJECTIVE: Cranial computed tomography (CT) scans are frequently obtained in the
      evaluation of blunt head trauma in children. These scans may detect unexpected
      incidental findings. The objectives of this study were to determine the
      prevalence and significance of incidental findings on cranial CT scans in
      children evaluated for blunt head trauma. METHODS: This was a secondary analysis
      of a multicenter study of pediatric blunt head trauma. Patients <18 years of age
      with blunt head trauma were eligible, with those undergoing cranial CT scan
      included in this substudy. Patients with coagulopathies, ventricular shunts,
      known previous brain surgery or abnormalities were excluded. We abstracted
      radiology reports for nontraumatic findings. We reviewed and categorized findings
      by their clinical urgency. RESULTS: Of the 43,904 head-injured children enrolled
      in the parent study, 15,831 underwent CT scans, and these latter patients serve
      as the study cohort. On 670 of these scans, nontraumatic findings were
      identified, with 16 excluded due to previously known abnormalities or surgeries.
      The remaining 654 represent a 4% prevalence of incidental findings. Of these, 195
      (30%), representing 1% of the overall sample, warranted immediate intervention or
      outpatient follow-up. CONCLUSIONS: A small but important number of children
      evaluated with CT scans after blunt head trauma had incidental findings.
      Physicians who order cranial CTs must be prepared to interpret incidental
      findings, communicate with families, and ensure appropriate follow-up. There are
      ethical implications and potential health impacts of informing patients about
      incidental findings.

PMID- 23878056
TI  - Development of a novel smart scaffold for human skeletal muscle regeneration.
AB  - Skeletal muscle defects are notoriously difficult to manage and the current
      methods used are associated with many limitations. Engineered skeletal muscle
      tissue has the potential to provide a solution that circumvents these
      disadvantages. Our previous work has identified a novel three-dimensionally
      aligned degradable phosphate glass fibre scaffold that can support myoblast
      differentiation and maturation. This current study has further developed the
      scaffold by encasing the fibres within a collagen gel to produce a smart
      composite scaffold that provides key biomimetic cues and supports the formation
      of a tissue that may be implanted in vivo. The constructs formed were
      approximately 30 mm long and microscopic examination confirmed favourable
      unidirectional cell alignment. There was good cell survival, and gene expression
      studies demonstrated upregulation of the myogenic regulatory factors and
      developmental and adult myosin heavy chain isoforms indicating myofibre formation
      and maturation respectively. Compared with the three-dimensional glass fibre
      scaffolds, the composite scaffolds had later gene upregulation, however, the use
      of collagen gels reinforced with degradable aligned glass fibres offers the
      opportunity to create a tissue analogue that can be easily manipulated.
      Furthermore, the glass fibre ends could support tendon/bone formation, and the
      channels formed as the fibres degrade could allow for vascular ingrowth.

PMID- 23878057
TI  - Dynamic metabolic imaging of hyperpolarized [2-(13) C]pyruvate using spiral
      chemical shift imaging with alternating spectral band excitation.
AB  - PURPOSE: In contrast to [1-(13) C]pyruvate, hyperpolarized [2-(13) C]pyruvate
      permits the ability to follow the (13) C label beyond flux through pyruvate
      dehydrogenase complex and investigate the incorporation of acetyl-coenzyme A into
      different metabolic pathways. However, chemical shift imaging (CSI) with [2-(13)
      C]pyruvate is challenging owing to the large spectral dispersion of the
      resonances, which also leads to severe chemical shift displacement artifacts for
      slice-selective acquisitions. METHODS: This study introduces a sequence for three
      dimensional CSI of [2-(13) C]pyruvate using spectrally selective excitation of
      limited frequency bands containing a subset of metabolites. Dynamic CSI data were
      acquired alternately from multiple frequency bands in phantoms for sequence
      testing and in vivo in rat heart. RESULTS: Phantom experiments verified the
      radiofrequency pulse design and demonstrated that the signal behavior of each
      group of resonances was unaffected by excitation of the other frequency bands.
      Dynamic three-dimensional (13) C CSI data demonstrated the sequence capability to
      image pyruvate, lactate, acetylcarnitine, glutamate, and acetoacetate, enabling
      the analysis of organ-specific spectra and metabolite time courses. CONCLUSIONS:
      The presented method allows CSI of widely separated resonances without chemical
      shift displacement artifact, acquiring multiple frequency bands alternately to
      obtain dynamic time-course information. This approach enables robust imaging of
      downstream metabolic products of acetyl-coenzyme A with hyperpolarized [2-(13)
      C]pyruvate.

PMID- 23878058
TI  - The effect of participating in a trauma- and stressful event-focused study.
AB  - OBJECTIVE: Researchers have increasingly examined whether participants who have
      experienced a traumatic event should be considered vulnerable research
      populations. Studies have typically asked participants in trauma-focused research
      whether they were upset by the study or perceived any benefit from it. The
      current study extends such research by measuring mood and exploring potential
      moderators of the impact of study participation. METHOD: Participants were 107
      women who experienced a traumatic or stressful event and completed an event
      focused research protocol. Negative affect was measured, using the Positive and
      Negative Affect Schedule, at the time of the study and 1 week later. RESULTS:
      Participants reported significantly lower levels of negative affect in the week
      after the study than before it. Decreases in negative affect were greatest for
      those with highest levels of depression at the time of interview. CONCLUSIONS:
      Participation in a trauma- or stressful-event-focused study is not harmful and
      may even be beneficial, especially among depressed participants.

PMID- 23878059
TI  - LHRH-PE40 fusion protein tethered silica nanorattles for imaging-guided tumor
      specific drug delivery and bimodal therapy.
AB  - Docyanine green (ICG) and LHRH-PE40 fusion protein are tethered onto drug
      carriers of silica nanorattles for imaging-guided tumor-specific drug delivery
      and bimodal therapy. The synergistic therapeutic effect of toxin PE40 and the
      chemotherapeutic drug docetaxel (Dtxl), specifically directed by LHRH to cancer,
      improves cancer treatment. Simultaneously, ICG enables real-time monitoring of
      the silica nanocomposites and therapeutic response. 

PMID- 23878060
TI  - Sonographic diagnosis of subungual intraosseous epidermoid cyst.
AB  - Intraosseous epidermoid cyst is an uncommon subungual mass. We report the
      sonographic findings in a case of intraosseous epidermoid cyst, which showed the
      characteristic whorled pattern of layers, previously described in other locations
      and unequivocally clinched the diagnosis in favor of this benign etiology and
      guided the management to phalangeal-sparing surgery.

PMID- 23878061
TI  - SND1 affects proliferation of hepatocellular carcinoma cell line SMMC-7721 by
      regulating IGFBP3 expression.
AB  - Staphylococcal nuclease domain containing 1 (SND1) is a ubiquitously expressed
      multifunctional protein involved in transcriptional regulation, RNA splicing and
      RNA metabolism. Ectopic expression of SND1 has been observed in various tumors
      including colon cancer, breast cancer, prostate cancer and hepatocellular
      carcinoma (HCC), indicating a positive role of SND1 in tumor initiation and
      progression. However, the exact role of SND1 in cancers has not been thoroughly
      investigated. In the present study, we investigated the role of SND1 in HCC.
      Immunohistochemistry analysis revealed that the expression level of SND1 was
      higher in HCC tissues than in adjacent nontumor tissues. Stable knock-down of
      SND1, performed on the HCC cell line SMMC-7721 using shRNA lentiviral expression
      system, led to reduced cell proliferation, clone formation and tumor formation in
      nude mice. The insulin-like growth factor (IGF) signaling pathway was frequently
      dysregulated in HCC, which could facilitate tumor progression. Screening of gene
      expression levels of the IGF pathway, using real-time PCR, revealed that a
      decrease in SND1 expression could increase the expression of IGF-binding protein
      3 (IGFBP3), which can negatively regulate activation of the IGF pathway by
      restricting interactions between IGF and IGF receptors. Results from previous
      studies showed that the downregulation of IGFBP3 expression is a common feature
      in HCC, and the upregulation of IGFBP3 expression could suppress HCC cells
      proliferation. We further confirmed that stable knock-down of IGFBP3 could
      promote SMMC-7721 cells proliferation. Therefore, we concluded that SND1 could
      affect SMMC-7721 cells proliferation by regulating IGFBP3 expression and IGF
      signaling pathway.

PMID- 23878062
TI  - Validation of planning-free vessel-encoded pseudo-continuous arterial spin
      labeling MR imaging as territorial-ASL strategy by comparison to super-selective
      p-CASL MRI.
AB  - PURPOSE: Vessel-encoded (VE) pseudo-continuous arterial spin labeling (p-CASL) is
      a territorial ASL (T-ASL) technique to identify the perfusion territories of
      cerebral arteries. The aim of this study was to validate the output of three
      Vessel-encoded p-CASL image processing methods, k-means clustering with and
      without subsequent linear analysis and a Bayesian framework, by comparison with
      the perfusion maps acquired with super-selective p-CASL. METHODS: The comparison
      was done quantitatively using the Hausdorff distance and Dice similarity
      coefficient in the territories of the right and left internal carotid arteries,
      the basilar artery, and the right and left vertebral arteries. A qualitative
      comparison was done in the areas of the anterior and posterior circulation, and
      the deep gray matter. RESULTS: The overall agreement between the Vessel-encoded p
      CASL image processing methods and super-selective p-CASL was good; with the
      difference that the linear analysis and the Bayesian framework were able to
      detect mixed perfusion. CONCLUSION: Planning-free Vessel-encoded p-CASL with k
      means clustering appears suitable as a general purpose T-ASL strategy, but to
      determine mixed perfusion a combination with linear analysis, or the Bayesian
      framework is preferable, which are superior in this regard. To accurately
      determine the perfusion territory of a single vessel, super-selective p-CASL is
      still recommended.

PMID- 23878063
TI  - Search and rescue helicopter-assisted transfer of ST-elevation myocardial
      infarction patients from an island in the Baltic Sea: results from over 100
      rescue missions.
AB  - BACKGROUND: Since 2005, ST-elevation myocardial infarction (STEMI) patients from
      the island of Bornholm in the Baltic Sea have been transferred for primary
      percutaneous coronary intervention (pPCI) by an airborne service. We describe the
      result of pPCI as part of the Danish national reperfusion strategy offered to a
      remote island population. METHODS: In this observational study, patients from
      Bornholm (n=101) were compared with patients from the mainland (Zealand)
      (n=2495), who were grouped according to time intervals (<120, 121-180, >180 min).
      The primary endpoint was all-cause 30-day mortality. Individual-level data from
      the Central Population Registry provided outcome that was linked to our
      inhospital PCI database. RESULTS: Treatment delay was longer in patients from
      Bornholm (349 min (IQR 267-446)) vs Zealand (211 (IQR 150-315)) (p<0.001). In
      patients from Zealand, 30-day mortality did not increase with time intervals
      (p=0.176), whereas, long-term mortality did (~3 years) (p=0.007). Thirty-day
      mortality was similar for Bornholm and the overall Zealand group (5.9% vs 6.2%
      p=0.955). Early presenters (<180 min) from Zealand (37%) had similar 30-day (5.3%
      vs 5.9% p=0.789), but numerically reduced long-term mortality compared with
      Bornholm (12.8% vs 15.8% p=0.387). Age, female gender, diabetes, Killipclass >2
      and preprocedural thrombolysis in myocardial infarction (TIMI) flow 0/1
      independently predicted 30-day mortality, however, treatment delay did not.
      Postprocedural TIMI flow 3 predicted improved survival. CONCLUSIONS: In this
      small population of STEMI patients from a remote island, airborne transfer
      appears feasible and safe, and their 30-day mortality after pPCI comparable with
      that of the mainland population despite inherent reperfusion delay exceeding
      guidelines.

PMID- 23878064
TI  - Regional analgesia in the emergency department for hip fractures: survey of
      current UK practice and its impact on services in a teaching hospital.
AB  - INTRODUCTION: While the benefits of regional analgesia (RA) for preoperative pain
      relief in hip fracture (HF) in elderly patients are well recognised, this service
      is yet to be established in many UK emergency departments (EDs). We set out to
      discover how widely RA is adopted in the UK EDs. METHODS: In April-July 2010, we
      conducted a postal survey of 218 UK EDs, followed up with fax reminders for non
      respondents. RESULTS: A total of 147/218 (67%) EDs completed the survey. Sixty
      five (44%) respondents reported use of RA blocks for HF. The commonest stated
      reasons for not using RA were lack of trained staff (36%) or appropriate
      equipment (22%). RA users practiced femoral nerve block most widely (60% of EDs)
      followed by fascia iliaca compartment block (FICB) (22%). DISCUSSION: It is more
      a lack of trained staff and suitable equipment that prevents RA blocks being
      widely adopted in the UK. We advocate FICB in HF patients, which is an easy
      landmark-based block that can be safely performed by ED doctors. Our survey
      initiated multidisciplinary consultation and development of a protocol for
      preoperative FICB in HFs in our teaching hospital ED. CONCLUSIONS: RA for HFs is
      not widely used in UK EDs, proving that there is room for improvement .The
      finding that RA blocks are performed by the ED medical staff in 84% of the
      responding EDs practising RA was reassuring for developing the service in our
      hospital. FICB should be considered as an alternative to parenteral analgesia in
      adult patients with HF.

PMID- 23878065
TI  - Identification of a recurrent transforming UBR5-ZNF423 fusion gene in EBV
      associated nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer which
      is prevalent in southern China, south-east Asia and northern Africa. The
      development and stepwise progression of NPC involves accumulation of multiple
      gross genetic changes during the clonal expansion of Epstein-Barr virus (EBV)
      infected nasopharyngeal epithelial cell population. Here, using paired-end whole
      transcriptome sequencing, we discovered a number of chimeric fusion transcripts
      in a panel of EBV-positive tumour lines. Among these transcripts, a novel fusion
      of ubiquitin protein ligase E3 component n-recognin 5 (UBR5) on 8q22.3 and zinc
      finger protein 423 (ZNF423) on 16q12.1, identified from the NPC cell line C666-1,
      was recurrently detected in 12/144 (8.3%) of primary tumours. The fusion gene
      contains exon 1 of UBR5 and exons 7-9 of ZNF423 and produces a 94 amino acid
      chimeric protein including the original C-terminal EBF binding domain (ZF29-30)
      of ZNF423. Notably, the growth of NPC cells with UBR5-ZNF423 rearrangement is
      dependent on expression of this fusion protein. Knock-down of UBR5-ZNF423 by
      fusion-specific siRNA significantly inhibited the cell proliferation and colony
      forming ability of C666-1 cells. The transforming ability of UBR5-ZNF423 fusion
      was also confirmed in NIH3T3 fibroblasts. Constitutive expression of UBR5-ZNF423
      in NIH3T3 fibroblasts significantly enhanced its anchorage-independent growth in
      soft agar and induced tumour formation in a nude mouse model. These findings
      suggest that expression of UBR5-ZNF423 protein might contribute to the
      transformation of a subset of NPCs, possibly by altering the activity of EBFs
      (early B cell factors). Identification of the oncogenic UBR5-ZNF423 provides new
      potential opportunities for therapeutic intervention in NPC.

PMID- 23878066
TI  - Repeated immobilization stress increases expression of beta3 -adrenoceptor in the
      left ventricle and atrium of the rat heart.
AB  - Stress is a contributor of many cardiovascular diseases. Positive inotropic and
      chronotropic effects of catecholamines are regulated via beta-adrenergic
      receptors (ARs). Many reports exist concerning changes of cardiac beta1 - and
      beta2 -ARs in stress, but only a few deal with modulation of cardiac beta3 -AR.
      Our aim was to analyze the expression and binding sites of beta1 -, beta2 - and
      beta3 -ARs and adenylyl cyclase activity in the left ventricle, and beta3 -AR
      expression and binding in the left atrium of rats exposed to acute and chronic
      immobilization stress (IMO). The concentration of noradrenaline in the ventricle
      decreased, while adrenaline increased, especially after repeated IMO. The mRNA
      and protein levels, and binding sites of beta3 -subtype significantly rose
      following chronic IMO, while all parameters for beta2 -AR dropped after single
      and repeated exposure. Similarly, the mRNA levels and binding sites for beta3 
      subtype increased in the left atrium as a consequence of chronic IMO. The rise in
      beta3 -subtypes and a drop in beta2 -subtypes resulted in inhibition of adenylyl
      cyclase activity within the left ventricle. Taken together, among other factors,
      up-regulation of beta3 -AR could represent an adaptation mechanism, which might
      be related to altered physiological function of the left ventricle and atrium
      during prolonged emotional stress and might serve cardioprotective function
      during catecholamine overload.

PMID- 23878067
TI  - 3D soft metamaterials with negative Poisson's ratio.
AB  - Buckling is exploited to design a new class of three-dimensional metamaterials
      with negative Poisson's ratio. A library of auxetic building blocks is identified
      and procedures are defined to guide their selection and assembly. The auxetic
      properties of these materials are demonstrated both through experiments and
      finite element simulations and exhibit excellent qualitative and quantitative
      agreement. 

PMID- 23878068
TI  - The voodoo doll task: Introducing and validating a novel method for studying
      aggressive inclinations.
AB  - Aggression pervades modern life. To understand the root causes of aggression,
      researchers have developed several methods to assess aggressive inclinations. The
      current article introduces a new behavioral method-the voodoo doll task (VDT)
      that offers a reliable and valid trait and state measure of aggressive
      inclinations across settings and relationship contexts. Drawing on theory and
      research on the law of similarity and magical beliefs (Rozin, Millman, & Nemeroff
      [1986], Journal of Personality and Social Psychology, 50, 703-712), we propose
      that people transfer characteristics of a person onto a voodoo doll representing
      that person. As a result, causing harm to a voodoo doll by stabbing it with pins
      may have important psychological similarities to causing actual harm to the
      person the voodoo doll represents. Nine methodologically diverse studies (total N
      = 1,376) showed that the VDT had strong reliability, construct validity, and
      convergent validity. Discussion centers on the importance of magical beliefs in
      understanding the causes of aggressive inclinations.

PMID- 23878069
TI  - Medical student attitudes to the autopsy and its utility in medical education: a
      brief qualitative study at one UK medical school.
AB  - Attending postmortems enables students to learn anatomy and pathology within a
      clinical context, provides insights into effects of treatment and introduces the
      reality that patients die. Rates of clinical autopsies have declined and medical
      schools have cut obligatory autopsy sessions from their curricula making it
      difficult to assess medical student perceptions of, and attitudes towards, the
      educational value of autopsy. Our aim was to investigate these perceptions by
      designing a brief qualitative study comprising nominal technique and focus group
      discussions with Cambridge Graduate Course students, all of whom had attended
      autopsies. Three general themes emerged from the focus group discussions: the
      value of autopsy as a teaching tool and ways the experience could be improved,
      the initial impact of the mortuary and the autopsy itself, and the "emerging
      patient"-an emotional continuum running from cadaver to autopsy subject and
      living patient. Educational benefits of autopsy-based teaching included greater
      understanding of anatomy and physiology, greater appreciation of the role of
      other health care professionals and an enhanced appreciation of psycho-social
      aspects of medical practice. Students suggested improvements for ameliorating the
      difficult emotional consequences of attendance. We conclude that autopsy-based
      teaching represents a low-cost teaching technique which is highly valued by
      students and has application to many diverse medical specialties and skills.
      However, careful preparation and organization of sessions is required to maximize
      potential educational benefits and reduce any negative emotional impact.

PMID- 23878070
TI  - Dynamic contrast enhanced MRI parameters and tumor cellularity in a rat model of
      cerebral glioma at 7 T.
AB  - PURPOSE: To test the hypothesis that a noninvasive dynamic contrast enhanced MRI
      (DCE-MRI) derived interstitial volume fraction (ve ) and/or distribution volume
      (VD ) were correlated with tumor cellularity in cerebral tumor. METHODS: T1 
      weighted DCE-MRI studies were performed in 18 athymic rats implanted with U251
      xenografts. After DCE-MRI, sectioned brain tissues were stained with Hematoxylin
      and Eosin for cell counting. Using a Standard Model analysis and Logan graphical
      plot, DCE-MRI image sets during and after the injection of a gadolinium contrast
      agent were used to estimate the parameters plasma volume (vp ), forward transfer
      constant (K(trans) ), ve , and VD . RESULTS: Parameter values in regions where
      the standard model was selected as the best model were: (mean +/- S.D.): vp =
      (0.81 +/- 0.40)%, K(trans) = (2.09 +/- 0.65) * 10(-2) min(-1) , ve = (6.65 +/-
      1.86)%, and VD = (7.21 +/- 1.98)%. The Logan-estimated VD was strongly correlated
      with the standard model's vp + ve (r = 0.91, P < 0.001). The parameters, ve
      and/or VD , were significantly correlated with tumor cellularity (r >= -0.75, P <
      0.001 for both). CONCLUSION: These data suggest that tumor cellularity can be
      estimated noninvasively by DCE-MRI, thus supporting its utility in assessing
      tumor pathophysiology.

PMID- 23878071
TI  - Stress-reduction interventions in an Australian university: a case study.
AB  - We examined the effects of awareness of stress-reduction interventions on
      employee well-being and work attitudes using a mixed methods design. Cross
      sectional data are presented from 247 employees who completed questionnaires in
      2004 at one Australian university. Analyses indicated that employees, who
      reported that interventions had been undertaken, scored higher on job
      satisfaction, affective organizational commitment, perceived procedural justice
      and trust in senior management than those who were not aware of the measures,
      although they did not differ in psychological strain. Details of the stress
      reduction interventions implemented by the Occupational Health and Safety
      department at the university are also reported. Thematic analyses of the
      perceived causes of both decreases and increases in stress for employees showed
      that staff reported workload and staffing pressures as key sources of increases
      in stress. On the other hand, new supervisors and/or management were identified
      as sources of decreased stress. Areas for consideration in future efforts to
      develop and refine stress interventions are also discussed.

PMID- 23878072
TI  - Clinical and biological significance of hepatoma-derived growth factor in Ewing's
      sarcoma.
AB  - We sought to investigate the clinicopathological significance and biological
      function of hepatoma-derived growth factor (HDGF) in Ewing's sarcoma. Our results
      showed that HDGF expression is up-regulated in Ewing's sarcoma. Nuclear HDGF
      expression is significantly associated with tumour volume (p < 0.001), metastases
      at diagnosis (p < 0.001), low overall survival rate (p < 0.001) and low disease
      free survival rate (p < 0.001). HDGF knock-down results in significant reduction
      of Ewing's sarcoma cell growth, proliferation and enhances tumourigenesis, both
      in vitro and in vivo. Meanwhile, HDGF knock-down causes cell cycle arrest and
      enhanced sensitization to serum starvation-induced apoptosis. Furthermore,
      recombinant HDGF promotes proliferation and colony formation of Ewing's sarcoma
      cells. Ninety-eight candidate HDGF downstream genes were identified in Ewing's
      sarcoma cells using cDNA microarray analysis. In addition, we found that HDGF
      knock-down inhibited FLI1 expression in Ewing's sarcoma cells at the mRNA and
      protein levels. Our findings suggest that HDGF exhibits oncogenic properties and
      may be a novel prognostic factor in Ewing's sarcoma. Targeting HDGF might be a
      potential therapeutic strategy for Ewing's sarcoma.

PMID- 23878073
TI  - A Study of 5-(1,2,4-Triazol-C-yl)tetrazol-1-ols: Combining the Benefits of
      Different Heterocycles for the Design of Energetic Materials.
AB  - The synthesis and full structural and spectroscopic characterization of three 5
      (1,2,4-triazol-C-yl)tetrazol-1-ol compounds with selected energetic moieties
      including nitrimino (5), nitro (6) and azido (7) groups are reported. The
      influence of those energetic moieties as well as the C-C connection of a tetrazol
      1-ol and a 1,2,4-triazole on structural and energetic properties has been
      investigated. All compounds were well characterized by various means, including
      IR and multinuclear NMR spectroscopy, mass spectrometry, and DSC. The molecular
      structures of 5-8 were determined in the solid state by single-crystal X-ray
      diffraction. The standard heats of formation were calculated on the CBS-4M level
      of theory utilizing the atomization energy method, revealing highly positive
      values for all compounds. The detonation parameters were calculated with the
      EXPLO5 program and compared to the common secondary explosive RDX. Additionally,
      sensitivities towards impact, friction and electrostatic discharge were
      determined.

PMID- 23878074
TI  - MicroRNAs in the tumour microenvironment: big role for small players.
AB  - MicroRNAs (miRNAs) represent a class of small non-coding RNAs with an important
      regulatory role in various physiological processes as well as in several
      pathologies including cancers. It is noteworthy that recent evidence suggests
      that the regulatory role of miRNAs during carcinogenesis is not limited to the
      cancer cells but they are also implicated in the activation of tumour stroma and
      its transition into a cancer-associated state. Results from experimental studies
      involving cells cultured in vitro and mice bearing experimental tumours,
      corroborated by profiling of clinical cancers for miRNA expression, underline
      this role and identify miRNAs as a potent regulator of the crosstalk between
      cancer and stroma cells. Considering the fundamental role of the tumour
      microenvironment in determining both the clinical characteristics of the disease
      and the efficacy of anticancer therapy, miRNAs emerge as an attractive target
      bearing important prognostic and therapeutic significance during carcinogenesis.
      In this article, we will review the available results that underline the role of
      miRNAs in tumour stroma biology and emphasise their potential value as tools for
      the management of the disease.

PMID- 23878076
TI  - Anatomy adventure: a board game for enhancing understanding of anatomy.
AB  - Certain negative factors such as fear, loss of concentration and interest in the
      course, lack of confidence, and undue stress have been associated with the study
      of anatomy. These are factors most often provoked by the unusually large
      curriculum, nature of the course, and the psychosocial impact of dissection. As a
      palliative measure, Anatomy Adventure, a board game on anatomy was designed to
      reduce some of these pressures, emphasize student centered and collaborative
      learning styles, and add fun to the process of learning while promoting
      understanding and retention of the subject. To assess these objectives, 95 out of
      over 150 medical and dental students who expressed willingness to be part of the
      study were recruited and divided into a Game group and a Non-game group. A
      pretest written examination was given to both groups, participants in the Game
      group were allowed to play the game for ten days, after which a post-test
      examination was also given. A 20-item questionnaire rated on a three-point scale
      to access student's perception of the game was given to the game group. The post
      test scores of the game group were significantly higher (P < 0.05) than those of
      the non-game counterparts. Also the post-test score of the game based group was
      significantly better (P < 0.05) than their pretest. The students in their
      feedback noted in very high proportions that the game was interesting, highly
      informative, encouraged team work, improved their attitude, and perception to
      gross anatomy.

PMID- 23878077
TI  - Testing predictions from the male control theory of men's partner violence.
AB  - The aim of this study was to test predictions from the male control theory of
      intimate partner violence (IPV) and Johnson's [Johnson, M. P. (1995). Journal of
      Marriage and the Family, 57, 282-294] typology. A student sample (N = 1,104)
      reported on their use of physical aggression and controlling behavior, to
      partners and to same-sex non-intimates. Contrary to the male control theory,
      women were found to be more physically aggressive to their partners than men
      were, and the reverse pattern was found for aggression to same-sex non-intimates.
      Furthermore, there were no substantial sex differences in controlling behavior,
      which significantly predicted physical aggression in both sexes. IPV was found to
      be associated with physical aggression to same-sex non-intimates, thereby
      demonstrating a link with aggression outside the family. Using Johnson's
      typology, women were more likely than men to be classed as "intimate terrorists,"
      which was counter to earlier findings. Overall, these results do not support the
      male control theory of IPV. Instead, they fit the view that IPV does not have a
      special etiology, and is better studied within the context of other forms of
      aggression.

PMID- 23878075
TI  - Three-dimensional Fourier encoding of simultaneously excited slices: generalized
      acquisition and reconstruction framework.
AB  - PURPOSE: Simultaneous multislice (SMS) acquisitions have recently received much
      attention as a means of increasing single-shot imaging speed. SMS acquisitions
      combine the advantages of single-shot sampling and acceleration along the slice
      dimension which was previously limited to three-dimensional (3D) volumetric
      acquisitions. A two-dimensional description of SMS sampling and reconstruction
      has become established in the literature. Here, we present a more general 3D
      Fourier encoding and reconstruction formalism for SMS acquisitions that can
      easily be applied to non-Cartesian SMS acquisitions. THEORY AND METHODS: An "SMS
      3D" k-space is defined in which the field of view along the slice select
      direction is equal to the number of excited slices times their separation. In
      this picture, SMS acceleration can be viewed as an undersampling of SMS 3D k
      space that can be freely distributed between the in-plane and slice directions as
      both are effective phase-encoding directions. RESULTS: Use of the SMS 3D k-space
      picture is demonstrated in phantom and in vivo brain acquisitions including data
      obtained with blipped-controlled aliasing in parallel imaging sampling. SMS
      sensitivity encoding reconstruction is demonstrated as well as non-Cartesian SMS
      imaging using blipped spiral trajectories. CONCLUSIONS: The full framework of
      reconstruction methods can be applied to SMS acquisitions by employing a 3D k
      space approach. The blipped-controlled aliasing in parallel imaging method can be
      viewed as a special case of undersampling an SMS 3D k-space. The extension of SMS
      methods to non-Cartesian 3D sampling and reconstruction is straightforward.

PMID- 23878078
TI  - Histone deacetylase AtHDA7 is required for female gametophyte and embryo
      development in Arabidopsis.
AB  - Histone modifications are involved in the regulation of many processes in
      eukaryotic development. In this work, we provide evidence that AtHDA7, a HISTONE
      DEACETYLASE (HDAC) of the Reduced Potassium Dependency3 (RPD3) superfamily, is
      crucial for female gametophyte development and embryogenesis in Arabidopsis
      (Arabidopsis thaliana). Silencing of AtHDA7 causes degeneration of micropylar
      nuclei at the stage of four-nucleate embryo sac and delay in the progression of
      embryo development, thereby bringing the seed set down in the Athda7-2 mutant.
      Furthermore, AtHDA7 down- and up-regulation lead to a delay of growth in
      postgermination and later developmental stages. The Athda7-2 mutation that
      induces histone hyperacetylation significantly increases the transcription of
      other HDACs (AtHDA6 and AtHDA9). Moreover, silencing of AtHDA7 affects the
      expression of ARABIDOPSIS HOMOLOG OF SEPARASE (AtAESP), previously demonstrated
      to be involved in female gametophyte and embryo development. However, chromatin
      immunoprecipitation analysis with acetylated H3 antibody provided evidence that
      the acetylation levels of H3 at AtAESP and HDACs does not change in the mutant.
      Further investigations are essential to ascertain the mechanism by which AtHDA7
      affects female gametophyte and embryo development. 

PMID- 23878079
TI  - Cryptogein-induced transcriptional reprogramming in tobacco is light dependent.
AB  - The fungal elicitor cryptogein triggers a light-dependent hypersensitive response
      in tobacco (Nicotiana tabacum). To assess the effect of light on this nonhost
      resistance in more detail, we studied various aspects of the response under dark
      and light conditions using the tobacco-cryptogein experimental system. Here, we
      show that light drastically alters the plant's transcriptional response to
      cryptogein, notably by dampening the induction of genes involved in multiple
      processes, such as ethylene biosynthesis, secondary metabolism, and glutathione
      turnover. Furthermore, chlorophyll fluorescence measurements demonstrated that
      quantum yield and functioning of the light-harvesting antennae decreased
      simultaneously, indicating that photoinhibition underlies the observed decreased
      photosynthesis and that photooxidative damage might be involved in the
      establishment of the altered response. Analysis of the isomer distribution of
      hydroxy fatty acids illustrated that, in the light, lipid peroxidation was
      predominantly due to the production of singlet oxygen. Differences in (reduced)
      glutathione concentrations and the rapid development of symptoms in the light
      when cryptogein was coinfiltrated with glutathione biosynthesis inhibitors
      suggest that glutathione might become a limiting factor during the cryptogein
      induced hypersensitive response in the dark and that this response might be
      modified by an increased antioxidant availability in the light. 

PMID- 23878080
TI  - RNA interference suppression of genes in glycosyl transferase families 43 and 47
      in wheat starchy endosperm causes large decreases in arabinoxylan content.
AB  - The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by
      arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes
      within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and
      IRX14) and GT47 (IRX10), have previously been shown to be involved in the
      synthesis of the xylan backbone in Arabidopsis, and close homologs of these have
      been implicated in the synthesis of xylan in other species. Here, homologs of
      IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy
      endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by
      a starchy endosperm-specific promoter. The total amount of AX was decreased by
      40% to 50% and the degree of arabinosylation was increased by 25% to 30% in
      transgenic lines carrying either of the transgenes. The cell walls of starchy
      endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed
      decreased immunolabeling for xylan and arabinoxylan epitopes and approximately
      50% decreased cell wall thickness compared with controls. The proportion of AX
      that was water soluble was not significantly affected, but average AX polymer
      chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics.
      However, the long AX chains seen in controls were absent in TaGT43_2 RNAi
      transgenics but still present in TaGT47_2 RNAi transgenics. The results support
      an emerging picture of IRX9-like and IRX10-like proteins acting as key components
      in the xylan synthesis machinery in both dicots and grasses. Since AX is the main
      component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of
      major importance to human nutrition. 

PMID- 23878081
TI  - Issue editors' notes.

PMID- 23878083
TI  - Social capital: its constructs and survey development.
AB  - This article reports on experiences and methods of adapting a valid adult social
      capital assessment to youth audiences in order to measure social capital and
      sense of place. The authors outline the process of adapting, revising,
      prepiloting, piloting, and administering a youth survey exploring young people's
      sense of community, involvement in the community, and the development of social
      capital. They then discuss the trade-offs of defining the often amorphous
      concepts included in social capital as they select measurement scales. The
      constructs used in the survey are agency, belonging, engagement, and trust for
      bonding, bridging, and linking forms of social capital. 

PMID- 23878084
TI  - Measuring social capital change using ripple mapping.
AB  - This article provides a detailed description of how to implement a ripple mapping
      activity to assess youth program effects on community capital and concludes with
      examples from Maine and Kansas. The maps lead to group reflection on project
      outcomes and further research and evaluation questions for group members. The
      results from five Maine communities showed that youth in schools and community
      clubs promoted intentional, mutually beneficial relationships with community
      groups and businesses and increased shared action on community projects.
      Likewise, youth in five small Kansas towns implemented and evaluated health
      promotion projects and found through mapping that youth built social capital in
      addition to awareness, knowledge, and skills in community health promotion.
      Ripple mapping helped to demonstrate that actions of youth-adult partnerships in
      both states improved the built, human, and social capital in small towns. 

PMID- 23878085
TI  - Social capital and youth development: toward a typology of program practices.
AB  - As part of our inquiry into how youth development and 4-H programming can affect
      the development of social capital for youth and for the community, we engaged
      youth in ripple mapping. Based on this information, we provide a typology of
      participation structures in youth development activities and the expected
      bridging and bonding social capital outcomes for each type. This article outlines
      the key factors underlying the typology and discusses strategies for using the
      typology to expand the impact of youth development and 4-H programming on young
      people and communities. It also outlines potential implications for increasing
      opportunities for fostering social capital leading to a spiraling-up effect for
      youth, volunteers, and the community. 

PMID- 23878086
TI  - Using multiple youth programming delivery modes to drive the development of
      social capital in 4-H participants.
AB  - This article focuses on how 4-H youth participants are building social capital,
      or connections among individuals and community members, through their 4-H
      experiences. These experiences can be seen through the lens of such 4-H delivery
      modes as the traditional 4-H club, after-school programs, and school enrichment
      programs. In addition, other experiences such as leadership camps and conferences
      or activities in the local community afford youth the opportunity to build the
      relationships, trust, and respect reflective of social capital. Examples are
      derived from 4-H program participants-urban, suburban and rural youth-in Camden
      County, New Jersey. 

PMID- 23878087
TI  - A community development approach to service-learning: building social capital
      between rural youth and adults.
AB  - Using 4-H and FFA case study findings, this article explores how community
      service-learning supports the building of social capital between rural youth and
      adults and the positive effects on community viability. Key elements of practice
      form a community development approach to service-learning, which opens up
      doorways for youth to partner with adult leaders and decision makers, gain
      credibility as resources and problem solvers, address community issues, and raise
      awareness of the value of school- and community-based youth programs. Case study
      evidence suggests that rural 4-H and FFA youth and adults benefit from the
      bonding relationships they form through working together to solve community
      issues over time. Positive community outcomes are noted as well, including
      increased community capacity and community recognition. By focusing on social
      capital as a key outcome of community service-learning, 4-H youth and community
      development extension professionals, educators, and other practitioners have
      contributed to the viability of rural communities. 

PMID- 23878088
TI  - Social capital and vulnerability from the family, neighborhood, school, and
      community perspectives.
AB  - This article reviews research and offers program examples for developing social
      capital in youth with a range of vulnerabilities: emotional, physical, social,
      and developmental. Protective factors provided by developing social capital at
      the individual level include access to support networks, transition to
      employment, and community connectedness. The authors feature approaches from the
      cooperative extension system, which links university and community resources, and
      identify exemplary programs that support social capital development by
      intervening with families, schools, neighborhoods, and communities. 

PMID- 23878089
TI  - Engaging underrepresented youth populations in community youth development:
      tapping social capital as a critical resource.
AB  - For youth who are the most vulnerable to challenging community conditions, more
      limited opportunities, and poor health, educational and economic trajectories
      derive especially strong benefits from engagement in community youth development
      efforts. Although communities can benefit in powerful ways from the knowledge and
      insight of these youth populations, the experiences of vulnerable youth are often
      underrepresented in planning and decision making. This article draws on lessons
      learned from two communities that successfully engaged such youth in a community
      change initiative over four years. Key elements in creating the types of safe,
      supportive, and meaningful settings that promote young people's ongoing
      participation and leadership were intentionality and commitment; local knowledge
      of vulnerable populations; adult allies with key capacities; meaningful focus;
      resources for intensive outreach, relationship building, and youth support; and
      continuity of key adults. Each of these elements is described, identifying the
      ways they build on often underrecognized forms of social capital and offering
      lessons learned about engaging underserved youth populations in community youth
      development. 

PMID- 23878090
TI  - Engaging young people as a community development strategy in the Wisconsin
      Northwoods.
AB  - This chapter focuses on two remote rural communities that engaged young people in
      meaningful community development efforts to build social capital. One community
      connected youth to the assets of the community and created opportunities for
      young adults to strengthen social networks. The other created partnerships and
      networks to build intergenerational trust. Both communities intentionally engaged
      young people in these efforts in order to sustain their communities' economic
      vitality. 

PMID- 23878092
TI  - Optimization of the straightness measurements on rough surfaces by Monte Carlo
      simulation.
AB  - The straightness error of a coordinate measuring machine (CMM) is determined by
      measuring a rule standard. Thanks to a reversal technique, the straightness
      uncertainty of the CMM is theoretically dissociated from the straightness
      uncertainty of the rule. However, stochastic variations of the whole measurement
      system involve uncertainties of the CMM straightness error. To quantify these
      uncertainties, different sources of stochastic variations are listed with their
      associated probability density functions. Then Monte Carlo methods are performed
      first to quantify error and secondly to optimize measurement protocol. It is
      shown that a 5-measurement distance from 0.1 mm to each measurement coordinate
      allows a double reduction of uncertainties, principally due to the rule roughness
      amplitude (R(a) = 0.35 um) and because this optimal distance of 0.1 mm is equal
      to the autocorrelation length of the rule roughness. With this optimal
      configuration, the final uncertainly on the straightness error of the CMM studied
      is less than 1 um on the whole evaluated length of the rule (1 m). An algorithm,
      including Probe Tip Radius of the CMM and surface roughness of the piece, is
      finally proposed to increase CMM reliability by minimizing error measurements due
      to surface roughness of the measured piece.

PMID- 23878091
TI  - beta-Thalassemia due to intronic LINE-1 insertion in the beta-globin gene (HBB):
      molecular mechanisms underlying reduced transcript levels of the beta-globin(L1)
      allele.
AB  - We describe the molecular etiology of beta(+)-thalassemia that is caused by the
      insertion of the full-length transposable element LINE-1 (L1) into the intron-2
      of the beta-globin gene (HBB). The transcript level of the affected beta-globin
      gene was severely reduced. The remaining transcripts consisted of full-length,
      correctly processed beta-globin mRNA and a minute amount of three aberrantly
      spliced transcripts with a decreased half-life due to activation of the nonsense
      mediated decay pathway. The lower steady-state amount of mRNA produced by the
      beta-globin(L1) allele also resulted from a reduced rate of transcription and
      decreased production of full-length beta-globin primary transcripts. The promoter
      and enhancer sequences of the beta-globin(L1) allele were hypermethylated;
      however, treatment with a demethylating agent did not restore the impaired
      transcription. A histone deacetylase inhibitor partially reactivated the beta
      globin(L1) transcription despite permanent beta-globin(L1) promoter CpG
      methylation. This result indicates that the decreased rate of transcription from
      the beta-globin(L1) allele is associated with an altered chromatin structure.
      Therefore, the molecular defect caused by intronic L1 insertion in the beta
      globin gene represents a novel etiology of beta-thalassemia.

PMID- 23878093
TI  - Ruthenium-Arene-beta-Carboline Complexes as Potent Inhibitors of Cyclin-Dependent
      Kinase 1: Synthesis, Characterization and Anticancer Mechanism Studies.
AB  - A series of Ru(II)-arene complexes (1-6) of the general formula [(eta(6)
      arene)Ru(L)Cl]PF6 (arene=benzene or p-cymene; L=bidentate beta-carboline
      derivative, an indole alkaloid with potential cyclin-dependent kinases (CDKs)
      inhibitory activities) is reported. All the complexes were fully characterized by
      classical analytical methods, and three were characterized by X-ray
      crystallography. Hydrolytic studies show that beta-carboline ligands play a vital
      role in their aqueous behaviour. These complexes are highly active in vitro, with
      the most active complex 6 displaying a 3- to 12-fold higher anticancer activity
      than cisplatin against several cancer cell lines. Interestingly, the complexes
      are able to overcome cross-resistance to cisplatin, and show much lower
      cytotoxicity against normal cells. Complexes 1-6 may directly target CDK1,
      because they can block cells in the G2M phase, down-regulate the expression of
      CDK1 and cyclin B1, and inhibit CDK1/cyclin B in vitro. Further mechanism studies
      show that the complexes can effectively induce apoptosis through mitochondrial
      related pathways and intracellular reactive oxygen species (ROS) elevation.

PMID- 23878094
TI  - Accurate T(1) mapping for oxygen-enhanced MRI in the mouse lung using a segmented
      inversion-recovery ultrashort echo-time sequence.
AB  - PURPOSE: A segmented inversion-recovery module combined with the 2D ultrashort
      echo time radial technique is proposed that allows accurate pixel level T(1)
      mapping of mouse lung in vivo. METHODS: Numerical simulations were performed to
      estimate T(1) measurement accuracy and precision versus flip angle and signal-to
      noise ratio. Phantom measurements were used for protocol validation, where the
      segmented inversion-recovery ultrashort echo-time sequence was compared with the
      reference technique (inversion-recovery rapid acquisition with refocused echoes).
      The in vivo experiments were carried out on free-breathing C57 mice (n = 10),
      breathing first air and then oxygen. RESULTS: The simulations demonstrated the
      high potential of the technique for accurate and precise T(1) assessment. Phantom
      experiments showed good agreement for T(1) values measured with segmented
      inversion-recovery ultrashort echo-time and the reference technique. The in vivo
      experiment demonstrated the utility of the technique in oxygen-enhanced
      assessment, where small T(1) changes were detected with high precision.
      CONCLUSION: Segmented inversion-recovery ultrashort echo-time provides accurate,
      high resolution T(1) mapping of the lung parenchyma.

PMID- 23878095
TI  - Variability of areal surface topography parameters due to the change in surface
      orientation to measurement direction.
AB  - Several random surface topographies were analyzed. They were measured by optical
      (Talysurf CCI Lite) method. They represent one- and two-process anisotropic and
      isotropic surfaces. These surfaces were rotated of +/- 1 degrees  and +/- 2
      degrees  by two methods: on the plane table (before measurement) and virtually
      (after measurement) using the software TalyMap Gold. After each measurement or
      surface rotation, each surface was levelled. Then, the forms were removed using
      polynomial of the 3rd degree. Areal surface topography parameters from standard
      ISO 25178 were calculated. The relative deviations of parameters were determined.
      The tendency of surface topography changes characteristic to various surface
      types were analyzed. It was found that change in orientation to the measurement
      direction of both isotropic and anisotropic surfaces could be substantial source
      of the measurement uncertainty. Functional parameter Smr and also feature
      parameters Sda, Sha, Sdv, Shv, and Spd are the mostly sensitive on measurement
      orientation. Statistical amplitude parameters Sa and Sq are more stable than
      parameters describing maximum surface height, like Sz, Sp, and Sv. The effect of
      surface orientation to measurement direction on values of functional parameters
      from V group was small. It was shown that changes of Sdq, Sdr, and Spc parameters
      describing hybrid properties due to surface rotation before measurement were
      smaller than those caused by change in surface orientation after measurement.

PMID- 23878097
TI  - Evaluation of a nanoemulsion formulation strategy for oral bioavailability
      enhancement of danazol in rats and dogs.
AB  - The objective of this study was to determine whether nanoemulsion formulations
      constitute a viable strategy to improve the oral bioavailability of danazol, a
      compound whose poor aqueous solubility limits its oral bioavailability. Danazol
      containing oil-in-water nanoemulsions (NE) with and without cosurfactants
      stearylamine (SA) and deoxycholic acid (DCA) were prepared and characterized.
      Nanoemulsion droplets size ranging from 238 to 344 nm and with surface charges of
      -24.8 mV (NE), -26.5 mV (NE-DCA), and +27.8 mV (NE-SA) were reproducibly
      obtained. Oral bioavailability of danazol in nanoemulsions was compared with
      other vehicles such as PEG400, 1% methylcellulose (MC) in water (1% MC),
      Labrafil, and a Labrafil/Tween 80 (9:1) mixture, after intragastric
      administration to rats and after oral administration of NE-SA, a Labrafil
      solution, or a Danocrine(r) tablet to dogs. The absolute bioavailability of
      danazol was 0.6% (PEG400), 1.2% (1% MC), 6.0% (Labrafil), 7.5%
      (Labrafil/Tween80), 8.1% (NE-DCA), 14.8% (NE), and 17.4% (NE-SA) in rats, and
      0.24% (Danocrine), 6.2% (Labrafil), and 58.7% (NE-SA) in dogs. Overall, danazol
      bioavailability in any nanoemulsion was higher than any other formulation.
      Danazol bioavailability from NE and NE-SA was 1.8- to 2.2-fold higher than NE-DCA
      nanoemulsion and could be due to significant difference in droplet size.

PMID- 23878096
TI  - Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia
      and motor, language, and cognitive delays.
AB  - We describe the molecular and clinical characterization of nine individuals with
      recurrent, 3.4-Mb, de novo deletions of 3q13.2-q13.31 detected by chromosomal
      microarray analysis. All individuals have hypotonia and language and motor
      delays; they variably express mild to moderate cognitive delays (8/9), abnormal
      behavior (7/9), and autism spectrum disorders (3/9). Common facial features
      include downslanting palpebral fissures with epicanthal folds, a slightly bulbous
      nose, and relative macrocephaly. Twenty-eight genes map to the deleted region,
      including four strong candidate genes, DRD3, ZBTB20, GAP43, and BOC, with
      important roles in neural and/or muscular development. Analysis of the breakpoint
      regions based on array data revealed directly oriented human endogenous
      retrovirus (HERV-H) elements of ~5 kb in size and of >95% DNA sequence identity
      flanking the deletion. Subsequent DNA sequencing revealed different deletion
      breakpoints and suggested nonallelic homologous recombination (NAHR) between HERV
      H elements as a mechanism of deletion formation, analogous to HERV-I-flanked and
      NAHR-mediated AZFa deletions. We propose that similar HERV elements may also
      mediate other recurrent deletion and duplication events on a genome-wide scale.
      Observation of rare recurrent chromosomal events such as these deletions helps to
      further the understanding of mechanisms behind naturally occurring variation in
      the human genome and its contribution to genetic disease.

PMID- 23878098
TI  - Whole brain perfusion measurements using arterial spin labeling with multiband
      acquisition.
AB  - PURPOSE: The multiband (MB) excitation and reconstruction technique was both
      developed and evaluated for accelerated data acquisition of arterial spin
      labeling (ASL) to cover whole brain perfusion maps. THEORY AND METHODS: MB
      excitation was incorporated into a pulsed ASL (PASL) technique and compared with
      conventional single-band excitation PASL from healthy subjects, using a 32
      channel head receiver coil at 3 T. The MB de-aliasing performance and
      effectiveness in perfusion measurement were measured with varying MB acceleration
      factors and gaps between MB excitations. RESULTS: The MB PASL perfusion maps were
      in good agreement with the conventional single-band PASL maps at matched slices.
      The imaging coverage could be effectively extended with the MB technique by a
      factor up to 5. A gap as small as 3 cm between MB excitations resulted in a
      comparable ASL signal loss and temporal-signal-to-noise ratio with single-band
      PASL. CONCLUSION: The MB ASL technique is an effective method to evaluate whole
      brain perfusion because it minimizes the temporal spread of labeled spins across
      slices, resulting in more accurate perfusion measurements.

PMID- 23878099
TI  - Copper-catalyzed oxidative amination and allylic amination of alkenes.
AB  - Enamines and enamides are useful synthetic intermediates and common components of
      bioactive compounds. A new protocol for their direct synthesis by a net alkene C
      H amination and allylic amination by using catalytic Cu(II) in the presence of
      MnO2 is reported. Reactions between N-aryl sulfonamides and vinyl arenes furnish
      enamides, allylic amines, indoles, benzothiazine dioxides, and dibenzazepines
      directly and efficiently. Control experiments further showed that MnO2 alone can
      promote the reaction in the absence of a copper salt, albeit with lower
      efficiency. Mechanistic probes support the involvement of nitrogen-radical
      intermediates. This method is ideal for the synthesis of enamides from 1,1
      disubstituted vinyl arenes, which are uncommon substrates in existing oxidative
      amination protocols.

PMID- 23878100
TI  - Bond detectors for molecular dynamics simulations, Part I: Hydrogen bonds.
AB  - Charge sensitivity analysis in AMBER force-field resolution has been used in
      quest for detectors of hydrogen bonds (HBs). The process of HB formation was
      investigated on ab initio classical trajectories (B3LYP/6-31G*) of different
      nucleobase pairs. Several charge sensitivities, namely: electronegativity,
      hardness, Fukui function (FF), and polarization matrix, were analyzed. The global
      and constrained equilibria were considered. It was demonstrated that FF indices
      and polarization matrix elements are good detectors of HB formation.

PMID- 23878101
TI  - Novel mutations in SCO1 as a cause of fatal infantile encephalopathy and lactic
      acidosis.
AB  - Isolated cytochrome c oxidase (COX) deficiency is a common cause of mitochondrial
      disease, yet its genetic basis remains unresolved in many patients. Here, we
      identified novel compound heterozygous mutations in SCO1 (p.M294V, p.Val93*) in
      one such patient with fatal encephalopathy. The patient lacked the severe
      hepatopathy (p.P174L) or hypertrophic cardiomyopathy (p.G132S) observed in
      previously reported SCO1 cases, so we investigated whether allele-specific
      defects in SCO1 function might underlie the genotype-phenotype relationships.
      Fibroblasts expressing p.M294V had a relatively modest decrease in COX activity
      compared with those expressing p.P174L, whereas both SCO1 lines had marked copper
      deficiencies. Overexpression of known pathogenic variants in SCO1 fibroblasts
      showed that p.G132S exacerbated the COX deficiency, whereas COX activity was
      partially or fully restored by p.P174L and p.M294V, respectively. These data
      suggest that the clinical phenotypes in SCO1 patients might reflect the residual
      capacity of the pathogenic alleles to perform one or both functions of SCO1. 

PMID- 23878102
TI  - Nanoparticle systems as tools to improve drug delivery and therapeutic efficacy.
AB  - Nanoparticle-based drug delivery systems are appealing because, among other
      properties, they are easily manufactured and have the capacity to encapsulate a
      wide variety of drugs, many of which are not directly miscible with water. This
      review classifies nanoparticles into three broad categories based upon material
      composition: bio-inspired systems, synthetic systems, and inorganic systems. Each
      has distinct properties suitable for drug delivery applications, including their
      structure, composition, and pharmacokinetics (including clearance and uptake
      mechanisms), making each uniquely suitable for certain types of drugs.
      Furthermore, nanoparticles can be customized, making them ideal for a variety of
      applications. Advantages and disadvantages of the different systems are
      discussed. Strategies for improving nanoparticle efficacy include adding
      targeting agents on the nanoparticle surface, altering the degradation profile to
      control drug release, or PEGylating the surface to increase circulation times and
      reduce immediate clearance by the kidneys. The future of nanoparticle systems
      seems to be focused on further improving overall patient outcome by increasing
      delivery accuracy to the target area.

PMID- 23878103
TI  - Three-dimensional heart locator for whole-heart coronary magnetic resonance
      angiography.
AB  - PURPOSE: Coronary magnetic resonance angiography (MRA) is commonly performed with
      diaphragmatic navigator (NAV) gating to compensate for respiratory motion, but
      this approach is inefficient as data must be reacquired when it is outside the
      acceptance window. We therefore developed and validated a motion compensation
      technique based on three-dimensional (3D) spatial registration in which data are
      accepted throughout the respiratory cycle. METHODS: A novel respiratory motion
      compensation method was implemented that acquires a low-resolution 3D-image of
      the heart (3D-LOC) just prior to coronary MRA data acquisition. 3D-LOC volumes
      were registered to the first 3D-LOC to estimate the respiratory-induced heart
      motion and to modify the coronary MRA data and reconstruct motion-corrected
      images. Whole-heart coronary MRA datasets were acquired from nine healthy
      subjects using a diaphragmatic NAV and using 3D-LOC. RESULTS: There was no
      significant difference between the subjective image score of NAV and 3D-LOC in
      three main coronary branches. The vessel sharpness of 3D-LOC was higher than NAV
      in the right (0.44 +/- 0.08 vs. 0.49 +/- 0.08; P = 0.055) and left circumflex
      arteries (0.49 +/- 0.05 vs. 0.52 +/- 0.04; P = 0.039). Scan time for 3D-LOC was
      significantly shorter than NAV (4.3 +/- 0.6 vs. 8.3 +/- 2.3 min; P = 0.004).
      CONCLUSION: Compared to NAV gating, 3D-LOC for coronary MRA reduces scan time by
      nearly 50% without compromising image quality.

PMID- 23878105
TI  - Effects of hypoxia on pluripotency in murine iPS cells.
AB  - Retroviral transduction of four transcription factors (Oct4, Sox2, Klf4 and c
      Myc) or three factors, excluding c-Myc, has been shown to initiate a
      reprogramming process that results in the transformation of murine fibroblasts to
      induced pluripotent stem (iPS) cells, and there has been a rapid increase in the
      number of iPS cell-based preclinical trials. In this study, the effects of these
      transcription factors were evaluated regarding the growth and differentiation of
      murine iPS cells under hypoxia. Based on the results of RT-PCR and alizarin red S
      staining, there were no statistical differences in the growth and differentiation
      of iPS cells or the induction of iPS cells to osteoblasts under hypoxia between
      the transcription factor groups. Furthermore, the function of hypoxia inducible
      factors (HIFs) in murine iPS cells under hypoxia was investigated in relation to
      the morphology and expression of transcription factors using RT-PCR and Western
      blotting. The HIF-2alpha knockdown group exhibited a decrease in the colony size
      of the iPS cells. The HIF-2alpha or -3alpha knockdown group demonstrated a
      statistically significant decrease in the transcription factor expression
      compared to that observed in the control group. These results demonstrate that
      HIF-2alpha among HIFs is the most influential candidate for the maintenance of
      the pluripotency of murine iPS cells.

PMID- 23878104
TI  - An algorithm for evaluating potential tissue drug distribution in toxicology
      studies from readily available pharmacokinetic parameters.
AB  - Having an understanding of drug tissue accumulation can be informative in the
      assessment of target organ toxicities; however, obtaining tissue drug levels from
      toxicology studies by bioanalytical methods is labor-intensive and infrequently
      performed. Additionally, there are no described methods for predicting tissue
      drug distribution for the experimental conditions in toxicology studies, which
      typically include non-steady-state conditions and very high exposures that may
      saturate several processes. The aim was the development of an algorithm to
      provide semiquantitative and quantitative estimates of tissue-to-plasma
      concentration ratios (Kp ) for several tissues from readily available parameters
      of pharmacokinetics (PK) such as volume of distribution (Vd ) and clearance of
      each drug, without performing tissue measurement in vivo. The computational
      approach is specific for the oral route of administration and non-steady-state
      conditions and was applied for a dataset of 29 Genentech small molecules such as
      neutral compounds as well as weak and strong organic bases. The maximum success
      rate in predicting Kp values within 2.5-fold error of observed Kp values was 82%
      at low doses (<100 mg/kg) in preclinical species. Prediction accuracy was
      relatively lower with saturation at high doses (>=100 mg/kg); however, an
      approach to perform low-to-high dose extrapolations of Kp values was presented
      and applied successfully in most cases. An approach for the interspecies scaling
      was also applied successfully. Finally, the proposed algorithm was used in a case
      study and successfully predicted differential tissue distribution of two small
      molecule MET kinase inhibitors, which had different toxicity profiles in mice.
      This newly developed algorithm can be used to predict the partition coefficients
      Kp for small molecules in toxicology studies, which can be leveraged to optimize
      the PK drivers of tissue distribution in an attempt to decrease drug tissue
      level, and improve safety margins.

PMID- 23878107
TI  - RAZER: a pulse sequence for whole-brain bolus tracking at high frame rates.
AB  - PURPOSE: To introduce a pulse sequence that obtains whole-brain perfusion
      measurements at 1.7 mm isotropic voxel resolution by dynamic susceptibility
      contrast MRI bolus tracking despite using a temporal resolution of 10.3 s: RAdial
      kZ-blipped 3D GRE-echo-planar imaging (GRE-EPI) for whole-brain pERfusion
      (RAZER). METHODS: In RAZER, in-plane radial and through-plane 3D GRE-EPI
      Cartesian sampling was used to produce a 3D stack-of-stars k-space. In vivo scans
      on one healthy volunteer and one patient with Moyamoya disease were performed
      using RAZER and a typical 2D GRE-EPI pulse sequence as a reference standard.
      Agreement in perfusion metrics was reported using linear regression analysis and
      Bland-Altman plots. RESULTS: Sliding window reconstruction recovered dynamic
      information lost in the large temporal acquisition window of RAZER. Inline phase
      correction scans corrected N/2 ghosting artifacts and view-dependent phase
      variations. Whole-brain images of cerebral blood volume, cerebral blood flow, and
      mean transit time were calculated with RAZER at 1.7 mm isotropic voxel resolution
      and good reference standard agreement in both subjects when sliding window
      reconstruction was used (r(2) > 0.7, mean bias in mean transit time measurements
      < 0.5 s). CONCLUSIONS: Despite using a temporal resolution of 10.3 s, in vivo
      data indicates that RAZER is able to obtain whole-brain perfusion measurements at
      1.7 mm isotropic voxel resolution and good reference standard agreement.

PMID- 23878108
TI  - Flash rate discrimination in rats: rate bisection and generalization peak shift.
AB  - Two experiments were conducted to determine whether responding by albino rats can
      be brought under the stimulus control of different flash rates. In the first
      experiment, a conditional discrimination procedure was employed whereby two
      different flash rates (fast or slow) signaled the availability of reinforcement
      on one of two levers (left or right). Stimulus control emerged rapidly and
      improved with continued training. When intermediate flash rates were presented
      during probe sessions, the bisection point of the fast and slow flash rates was
      near their geometric mean, consistent with research employing other stimulus
      types. In the second experiment, a successive discrimination procedure was
      employed whereby responding in the presence of one flash rate (S(+) ) was
      reinforced while responding in the presence of another flash rate (S(-) ) was not
      reinforced. Again, stimulus control emerged quickly and improved with continued
      training. Test sessions in which many different flash rates were presented for
      brief periods in extinction revealed the peak shift phenomenon, in which peak
      response rates are shifted from the S(+) in a direction away from the S(-) .
      Flash rate is endorsed as a continuous stimulus dimension that is useful for
      differentially signaling schedule components. 

PMID- 23878109
TI  - American Skullcap (Scutellaria lateriflora): a randomised, double-blind placebo
      controlled crossover study of its effects on mood in healthy volunteers.
AB  - Scutellaria lateriflora, a traditional herbal remedy for stress and anxiety, was
      tested on human volunteers for its effects on mood. In a placebo-controlled,
      double-blind, crossover study, 43 healthy participants were randomised to a
      sequence of three times daily S. lateriflora (350 mg) or placebo, each over two
      weeks. In this relatively non-anxious population (81% were mildly anxious or
      less, i.e. Beck Anxiety Inventory (BAI) scores <= 15), there was no significant
      difference between skullcap and placebo with BAI (p = 0.191). However, there was
      a significant group effect (p = 0.049), suggesting a carryover effect of
      skullcap. For Total Mood Disturbance measured by the Profile of Mood States,
      there was a highly significant (p = <0.001) decrease from pre-test scores with
      skullcap but not placebo (p = 0.072). The limitations of carryover effect,
      generally low anxiety scores and differences in anxiety levels between groups at
      baseline (p = 0.022), may have reduced the chances of statistical significance in
      this study. However, as S. lateriflora significantly enhanced global mood without
      a reduction in energy or cognition, further study assessing its putative
      anxiolytic effects in notably anxious subjects with co-morbid depression is
      warranted.

PMID- 23878110
TI  - Memories of shame experiences with others and depression symptoms: the mediating
      role of experiential avoidance.
AB  - BACKGROUND: Shame experiences have been suggested to be related with
      psychopathological symptoms and with self-relevant beliefs. Recent studies also
      suggest that avoidant-focused strategies (e.g., rumination, thought suppression
      and dissociation) mediate the impact of shame memories and depression symptoms.
      However, experiential avoidance has been found to mediate the relation between
      early experience of abuse and psychopathological symptoms. Our goal was to test
      the mediating effect of experiential avoidance in the relation between both the
      nature of shame experiences at the hands of caregivers and the centrality of
      shame memories with others, and depression symptoms. METHOD: Using structural
      equation modelling, we assessed the frequency and nature of recalled shame
      experiences at the hands of caregivers, the centrality of shame experiences with
      others throughout childhood and adolescence, experiential avoidance and
      depression symptomatology in 161 participants from general population. RESULTS:
      Experiential avoidance mediates the impact of shame experiences with caregivers
      and depression symptoms. Experiential avoidance also mediated the association
      between the centrality of shame experiences with others and depression symptoms.
      CONCLUSION: Our results suggest that shame memories with others do not per se
      impact on depression symptoms, but rather the unwillingness to experience them
      and the attempts to control them. Hence, our results emphasize the importance of
      addressing affect regulation processes such as avoidance when dealing with shame
      memories, particularly with patients who experience depression symptoms. KEY
      PRACTITIONER MESSAGE: The recall of shame experiences with caregivers is
      associated with the experience of depression symptoms, even when these
      experiences are not perceived as central points to one's life identity and story.
      This seems to suggest a necessity to explore these experiences in a therapeutic
      setting. Our findings suggest that experiential avoidance is a key process
      through which these memories of shame experiences impact on depression
      symptomatology. Hence, it seems to be of great importance to reduce experiential
      avoidance and help people change the way they relate with these memories.

PMID- 23878111
TI  - A raw deal.

PMID- 23878112
TI  - Determinants of resident competence in mastoidectomy: role of interest and
      deliberate practice.
AB  - OBJECTIVES/HYPOTHESIS: This study explores the influence of selected factors on
      achievement of competency in mastoid surgery. STUDY DESIGN: A prospective study
      of surgical performance and a retrospective survey of learner and training
      factors. METHODS: The longitudinal performance of 15 residents was evaluated
      using the mastoidectomy task-based checklist (TBC). The influence of surgical
      experience, resident interest, and training factors (course attendance, voluntary
      use of simulation laboratory) was also examined and compared for the acquisition
      of distinct levels of technical skill difficulty (cortical mastoidectomy vs.
      facial recess). RESULTS: Ninety-six observations made during the first otology
      rotation were analyzed. Cortical mastoidectomy tasks showed positive associations
      with cumulated case numbers (OR 1.13, CI 1.04-1.23, P = .003) and interest in
      otology (OR 3.86, CI 1.21-12.27, P = .022). Facial recess tasks showed a larger
      positive association with interest in otology (OR 10.38, CI 2.25-47.94, P =
      .003), and negative association with extra time spent in laboratory practice (OR
      .05, CI 0.011-0.23, P = .000). CONCLUSIONS: Learning trajectory for cortical
      mastoidectomy and facial recess may be influenced by different factors. Interest
      in otology, in particular, may have a moderating effect on the acquisition of
      more complex skills in mastoid surgery. A negative association between self
      directed laboratory simulation and performance may reflect the impact of
      assessment-guided feedback in promoting deliberate practice. Further
      investigations are suggested to explore the interactions between individual
      trainee differences, educational models, and learning outcomes.

PMID- 23878113
TI  - Personalised cancer management: closer, but not here yet.

PMID- 23878114
TI  - Bringing precision medicine to the clinic: from genomic profiling to the power of
      clinical observation.

PMID- 23878115
TI  - Optimally tolerated dose of lapatinib in combination with docetaxel plus
      trastuzumab in first-line treatment of HER2-positive metastatic breast cancer.
AB  - BACKGROUND: This phase IB, open-label, dose-escalation study evaluated the
      safety, tolerability, and optimally tolerated regimen (OTR) of lapatinib in
      combination with docetaxel and trastuzumab in patients with previously untreated
      stage IV metastatic breast cancer (MBC) tumors overexpressing human epidermal
      growth factor receptor 2 (HER2). PATIENTS AND METHODS: Evaluated dose regimens
      included lapatinib (500-1500 mg/day), docetaxel (triweekly; 60-100 mg/m&sup2;),
      and trastuzumab (weekly; 2 mg/kg fixed dose); prophylactic granulocyte colony
      stimulating factor was included with regimens with >=750 mg/day lapatinib. End
      points included OTR and safety/tolerability (primary), overall response rate
      (ORR), and pharmacokinetics (secondary). RESULTS: None of the patients (N = 53)
      experienced dose-limiting toxic effects (DLTs) at the highest dose level; thus,
      the OTR of lapatinib with 100 mg/m(2) docetaxel was not determined. Common
      adverse events included diarrhea, nausea, alopecia, fatigue, and rash; grade 3/4
      (>=2 patients) were neutropenia, diarrhea, leukopenia, peripheral neuropathy, and
      rash. Seven patients had DLTs (cycle 1). In 45 patients with measurable disease
      confirmed by bone scan, investigator-assessed ORR was 31%; without bone scan,
      confirmation was 64%; 8 patients without measurable disease were evaluated as
      stable. Lapatinib/docetaxel plasma concentrations were positively associated with
      complete response. CONCLUSIONS: Lapatinib/docetaxel/trastuzumab is a feasible and
      well-tolerated treatment of untreated HER2-positive stage IV MBC. Two
      lapatinib/docetaxel OTR doses were recommended (1250 mg/75 mg/m&sup2;; 1000
      mg/100 mg/m&sup2;). CLINICAL TRIAL NUMBER: NCT00251433.

PMID- 23878116
TI  - Is intraductal papillary mucinous neoplasm associated with extrapancreatic
      malignancies? Which is the true, prevalence or incidence?

PMID- 23878117
TI  - Concern on quality-of-life analysis in the OPTIMAL study.

PMID- 23878118
TI  - Reply to 'Concern on quality-of-life analysis in the OPTIMAL study' by Couraud et
      al.

PMID- 23878120
TI  - A milestone.

PMID- 23878121
TI  - Overview of reviews in child health: evidence synthesis and the knowledge base
      for a specific population.
AB  - BACKGROUND: Overviews of reviews are an evolving form of evidence synthesis. The
      Cochrane Child Health Field has been producing overviews since 2006, during which
      time the methods that have been used have changed, both due to the development of
      guidance within The Cochrane Collaboration and to the decisions made by
      individual author teams. This paper studies the first 29 overviews published in
      EBCH. OBJECTIVES: To describe some aspects of the approaches taken in EBCH
      overviews to producing evidence syntheses relevant to the healthcare needs of
      children; to highlight the contribution that overviews can make to the knowledge
      base for treatment for a particular population. METHODS: Data was extracted on:
      whether the overview included systematic review (SR) data only, or also data from
      individual trials not present in the included SRs; name(s) of the Cochrane Review
      Group (CRG) that prepared the included SRs; topics of the overviews as compared
      to the topics of the included reviews; age-subgroup analyses presented in the
      overviews. RESULTS: In 23 overviews, all published in 2012, the authors included
      trial data as well as SR data; two overviews addressed conditions not explicitly
      addressed by the included reviews; three overviews included pre-specified age
      subgroup analyses. DISCUSSION: The aim of clinical relevance has been achieved by
      means such as: drawing from reviews produced by multiple CRGs; using SR evidence
      to explore clinically relevant topics that may not match exactly with the topics
      covered by the SRs; ensuring that the evidence in overviews is as up to date as
      possible by redoing searches and including trials not incorporated in the
      included SRs; and, where permitted by the data, using age-subgroup analyses to
      present the data in a way which matches the stages of childhood development.
      CONCLUSION: Overview authors are dependent on the nature of the data and methods
      reported in the included SRs. This suggests a need for further study about how
      SRs could be conducted in order to facilitate the conduct of overviews.

PMID- 23878122
TI  - Cochrane Review: Screening programmes for developmental dysplasia of the hip in
      newborn infants.
AB  - BACKGROUND: Uncorrected developmental dysplasia of the hip (DDH) is associated
      with long-term morbidity such as gait abnormalities, chronic pain and
      degenerative arthritis. OBJECTIVES: To determine the effect of different
      screening programmes for DDH on the incidence of late presentation of congenital
      hip dislocation. SEARCH METHODS: Searches were performed in CENTRAL (The Cochrane
      Library), MEDLINE and EMBASE (January 2011) supplemented by searches of clinical
      trial registries, conference proceedings, cross references and contacting expert
      informants. SELECTION CRITERIA: Randomised, quasi-randomised or cluster trials
      comparing the effectiveness of screening programmes for DDH. DATA COLLECTION AND
      ANALYSIS: Three independent review authors assessed study eligibility and
      quality, and extracted data. MAIN RESULTS: No study examined the effect of
      screening (clinical and/or ultrasound) and early treatment versus not screening
      and later treatment. One study reported universal ultrasound compared to clinical
      examination alone did not result in a significant reduction in late diagnosed DDH
      or surgery but was associated with a significant increase in treatment. One study
      reported targeted ultrasound compared to clinical examination alone did not
      result in a significant reduction in late diagnosed DDH or surgery, with no
      significant difference in rate of treatment. Meta-analysis of two studies found
      universal ultrasound compared to targeted ultrasound did not result in a
      significant reduction in late diagnosed DDH or surgery. There was heterogeneity
      between studies reporting the effect on treatment rate. Meta-analysis of two
      studies found delayed ultrasound and targeted splinting compared to immediate
      splinting of infants with unstable (but not dislocated) hips resulted in no
      significant difference in the rate of late diagnosed DDH. Both studies reported a
      significant reduction in treatment with use of delayed ultrasound and targeted
      splinting. One study reported delayed ultrasound and targeted splinting compared
      to immediate splinting of infants with mild hip dysplasia on ultrasound resulted
      in no significant difference in late diagnosed DDH but a significant reduction in
      treatment. No infants in either group received surgery. AUTHORS' CONCLUSIONS:
      There is insufficient evidence to give clear recommendations for practice. There
      is inconsistent evidence that universal ultrasound results in a significant
      increase in treatment compared to the use of targeted ultrasound or clinical
      examination alone. Neither of the ultrasound strategies have been demonstrated to
      improve clinical outcomes including late diagnosed DDH and surgery. The studies
      are substantially underpowered to detect significant differences in the uncommon
      event of late detected DDH or surgery. For infants with unstable hips or mildly
      dysplastic hips, use of delayed ultrasound and targeted splinting reduces
      treatment without significantly increasing the rate of late diagnosed DDH or
      surgery. PLAIN LANGUAGE SUMMARY: Screening methods for dislocated or improperly
      formed hips in newborn infants The hip joint is a ball and socket joint. Newborns
      may have hips that are not in their socket (dislocated) or hips that are
      improperly formed (dysplasia). Risk factors for hip dysplasia include a family
      history of a similar problem and female infants delivered in the breech position.
      The hips of most newborns will be examined clinically after birth and during
      infancy to determine whether they are stable, unstable or dislocated. Screening
      for hip dysplasia may prevent the need for late treatment, which is associated
      with long term hip deformity, gait disturbance and arthritis. However, early
      screening leads to increased treatment. Treatment may be complicated by damage to
      the hip due to impairment of the blood supply (avascular necrosis). This review
      found no studies that compared the benefits and costs of early screening versus
      not screening for hip problems. Studies that compared the addition of ultrasound
      to clinical examination reported that when ultrasound was performed on all
      infants, the rate of treatment increased with no significant difference in rate
      of late detected dysplasia or surgery. Targeted ultrasound to infants at high
      risk of hip dysplasia did not significantly increase the rate of treatment but
      also did not significantly reduce the rate of late detected dysplasia or surgery.
      It is not possible to give clear recommendations for hip screening of newborn
      infants from the available evidence. Where infants are clinically detected as
      having unstable but not dislocated hips, or are detected on ultrasound to have
      mild hip dysplasia, there is evidence that delaying treatment by two to eight
      weeks reduces the need for treatment without a significant increase in late
      diagnosed dysplasia or surgery.

PMID- 23878123
TI  - Commentary on 'Screening programmes for developmental dysplasia of the hip in
      newborn infants' with response from review authors.

PMID- 23878124
TI  - Cochrane Review: Osmotic and stimulant laxatives for the management of childhood
      constipation (Review).
AB  - BACKGROUND: Constipation within childhood is an extremely common problem. Despite
      the widespread use of osmotic and stimulant laxatives by health professionals to
      manage constipation in children, there has been a long standing paucity of high
      quality evidence to support this practice. OBJECTIVES: We set out to evaluate the
      efficacy and safety of osmotic and stimulant laxatives used to treat functional
      childhood constipation. SEARCH METHODS: The search (inception to May 7, 2012) was
      standardised and not limited by language and included electronic searching
      (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane
      Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized
      Trials Register), reference searching of all included studies, personal contacts
      and drug companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) which
      compared osmotic or stimulant laxatives with either placebo or another
      intervention, with patients aged 0 to 18 years old were considered for inclusion.
      The primary outcome was frequency of defecation. Secondary endpoints included
      faecal incontinence, disimpaction, need for additional therapies and adverse
      events. DATA COLLECTION AND ANALYSIS: Relevant papers were identified and the
      authors independently assessed the eligibility of trials. Methodological quality
      was assessed using the Cochrane risk of bias tool.The Cochrane RevMan software
      was used for analyses. Patients with final missing outcomes were assumed to have
      relapsed. For continuous outcomes we calculated a mean difference (MD) and 95%
      confidence interval (CI) using a fixed-effect model. For dichotomous outcomes we
      calculated an odds ratio (OR) and 95% confidence intervals (95% CI) using a fixed
      effect model. The chi square and I(2) statistics were used to assess statistical
      heterogeneity. A random-effects model was used in situations of unexplained
      heterogeneity MAIN RESULTS: Eighteen RCTs (1643 patients) were included in the
      review. Nine studies were judged to be at high risk of bias due to lack of
      blinding, incomplete outcome data and selective reporting. Meta-analysis of two
      studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a
      significantly increased number of stools per week with PEG (MD 2.61 stools per
      week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled
      studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Meta
      analysis of 4 studies with 338 participants comparing PEG with lactulose showed
      significantly greater stools per week with PEG (MD 0.95 stools per week, 95% CI
      0.46 to 1.44), although follow up was short. Patients who received PEG were
      significantly less likely to require additional laxative therapies. Eighteen per
      cent of PEG patients required additional therapies compared to 30% of lactulose
      patients (OR 0.49, 95% CI 0.27 to 0.89). No serious adverse events were reported
      with either agent. Common adverse events in these studies included diarrhoea,
      abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies
      with 211 participants comparing PEG with milk of magnesia showed that the
      stools/wk was significantly greater with PEG (MD 0.69 stools per week, 95% CI
      0.48 to 0.89). However, the magnitude of this difference is quite small and may
      not be clinically significant. One child was noted to be allergic to PEG, but
      there were no other serious adverse events reported. Meta-analysis of 2 studies
      with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed
      a relatively large statistically significant difference in the number of stools
      per week favouring paraffin (MD 4.94 stools per week, 95% CI 4.28 to 5.61). No
      serious adverse events were reported. Adverse events included abdominal pain,
      distention and watery stools. No statistically significant differences in the
      number of stools per week were found between PEG and enemas (1 study, 90
      patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1
      study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P >
      0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to
      1.03), and PEG and liquid paraffin (1 study, 158 patients, MD 0.70, 95% CI -0.38
      to 1.78). AUTHORS' CONCLUSIONS: The pooled analyses suggest that PEG preparations
      may be superior to placebo, lactulose and milk of magnesia for childhood
      constipation. GRADE analyses indicated that the overall quality of the evidence
      for the primary outcome (number of stools per week) was low or very low due to
      sparse data, inconsistency (heterogeneity), and high risk of bias in the studies
      in the pooled analyses. Thus, the results of the pooled analyses should be
      interpreted with caution because of quality and methodological concerns, as well
      as clinical heterogeneity, and short follow up. However, PEG appears safe and
      well tolerated. There is also evidence suggesting the efficacy of liquid paraffin
      (mineral oil), which was also well tolerated.There is no evidence to demonstrate
      the superiority of lactulose when compared to the other agents studied, although
      there is a lack of placebo controlled studies. Further research is needed to
      investigate the long-term use of PEG for childhood constipation, as well as the
      role of liquid paraffin. PLAIN LANGUAGE SUMMARY: Laxatives for the management of
      childhood constipation Constipation within childhood is an extremely common
      problem. Despite the widespread use of laxatives by health professionals to
      manage constipation in children, there has been a long standing lack of evidence
      to support this practice. This review included eighteen studies with a total of
      1643 patients that compared nine different agents to either placebo (inactive
      medications) or each other. The results of this review suggest that polyethylene
      glycol preparations may increase the frequency of bowel motions in constipated
      children. Polyethylene glycol was generally safe, with lower rates of minor side
      effects compared to other agents. Common side effects included flatulence,
      abdominal pain, nausea, diarrhoea and headache. There was also some evidence that
      liquid paraffin (mineral oil) increased the frequency of bowel motions in
      constipated children and was also safe. Common side effects with liquid paraffin
      included abdominal pain, distention and watery stools. There was no evidence to
      suggest that lactulose is superior to the other agents studied, although there
      were no trials comparing it to placebo. The results of the review should be
      interpreted with caution due to methodological quality and statistical issues in
      the included studies. In addition, these studies were relatively short in
      duration and so it is difficult to assess the long-term effectiveness of these
      agents for the treatment of childhood constipation. Long-term effectiveness is
      important, given the often chronic nature of this problem in children.

PMID- 23878125
TI  - Commentary on 'Osmotic and stimulant laxatives for the management of childhood
      constipation'.

PMID- 23878126
TI  - Home fortification of foods with multiple micronutrient powders for health and
      nutrition in children under two years of age (Review).
AB  - BACKGROUND: Vitamin and mineral deficiencies, particularly those of iron, vitamin
      A and zinc, affect more than two billion people worldwide. Young children are
      highly vulnerable because of rapid growth and inadequate dietary practices.
      Micronutrient powders (MNP) are single-dose packets containing multiple vitamins
      and minerals in powder form that can be sprinkled onto any semi-solid food.The
      use of MNP for home or point-of-use fortification of complementary foods has been
      proposed as an intervention for improving micronutrient intake in children under
      two years of age. OBJECTIVES: To assess the effects and safety of home (point-of
      use) fortification of foods with multiple micronutrient powders on nutritional,
      health and developmental outcomes in children under two years of age. SEARCH
      METHODS: We searched the following databases in February 2011: Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (1948 to
      week 2 February 2011), EMBASE (1980 to Week 6 2011), CINAHL (1937 to current),
      CPCI-S (1990 to 19 February 2011), Science Citation Index (1970 to 19 February
      2011), African Index Medicus (searched 23 February 2011), POPLINE (searched 21
      February 2011), ClinicalTrials.gov (searched 23 February 2011), mRCT (searched 23
      February 2011), and World Health Organization International Clinical Trials
      Registry Platform (ICTRP) (searched 23 February 2011). We also contacted relevant
      organisations (25 January 2011) for the identification of ongoing and unpublished
      studies. SELECTION CRITERIA: We included randomised and quasi-randomised trials
      with either individual or cluster randomisation. Participants were children under
      the age of two years at the time of intervention, with no specific health
      problems. The intervention was consumption of food fortified at the point of use
      with multiple micronutrient powders formulated with at least iron, zinc and
      vitamin A compared with placebo, no intervention or the use of iron containing
      supplements, which is the standard practice. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed the eligibility of studies against the
      inclusion criteria, extracted data from included studies and assessed the risk of
      bias of the included studies. MAIN RESULTS: We included eight trials (3748
      participants) conducted in low income countries in Asia, Africa and the
      Caribbean, where anaemia is a public health problem. The interventions lasted
      between two and 12 months and the powder formulations contained between five and
      15 nutrients. Six trials compared the use of MNP versus no intervention or a
      placebo and the other two compared the use of MNP versus daily iron drops. Most
      of the included trials were assessed as at low risk of bias. Home fortification
      with MNP reduced anaemia by 31% (six trials, RR 0.69; 95% CI 0.60 to 0.78) and
      iron deficiency by 51% (four trials, RR 0.49; 95% CI 0.35 to 0.67) in infants and
      young children when compared with no intervention or placebo, but we did not find
      an effect on growth. In comparison with daily iron supplementation, the use of
      MNP produced similar results on anaemia (one trial, RR 0.89; 95% CI 0.58 to 1.39)
      and haemoglobin concentrations (two trials, MD -2.36 g/L; 95% CI -10.30 to 5.58);
      however, given the limited amount of data these results should be interpreted
      cautiously. No deaths were reported in the trials and information on side effects
      and morbidity, including malaria, was scarce. It seems that the use of MNP is
      efficacious among infants and young children six to 23 months of age living in
      settings with different prevalences of anaemia and malaria endemicity, regardless
      of whether the intervention lasts two, six or 12 months or whether recipients are
      male or female. AUTHORS' CONCLUSIONS: Home fortification of foods with multiple
      micronutrient powders is an effective intervention to reduce anaemia and iron
      deficiency in children six months to 23 months of age. The provision of MNP is
      better than no intervention or placebo and possibly comparable to commonly used
      daily iron supplementation. The benefits of this intervention as a child survival
      strategy or on developmental outcomes are unclear. Data on effects on malaria
      outcomes are lacking and further investigation of morbidity outcomes is needed.
      The micronutrient powders containing multiple nutrients are well accepted but
      adherence is variable and in some cases comparable to that achieved in infants
      and young children receiving standard iron supplements as drops or syrups.

PMID- 23878127
TI  - Commentary on 'Home fortification of foods with multiple micronutrient powders
      for health and nutrition in children under two years of age'.

PMID- 23878129
TI  - Commentary on 'Prophylactic phototherapy for preventing jaundice in preterm or
      low birth weight infants'.

PMID- 23878128
TI  - Cochrane Review: Prophylactic phototherapy for preventing jaundice in preterm or
      low birth weight infants.
AB  - BACKGROUND: Low birth weight and premature infants are at major risk for
      exaggerated hyperbilirubinaemia and jaundice that can lead to bilirubin
      encephalopathy. Phototherapy is the most common treatment for neonatal
      hyperbilirubinaemia and could be most effective in preventing the sequelae of
      hyperbilirubinaemia if initiated prophylactically. OBJECTIVES: To evaluate the
      efficacy and safety of prophylactic phototherapy for preterm (< 37 weeks
      gestational age) or low birth weight infants (birth weight < 2500 g). SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL,
      The Cochrane Library, Issue 3) on 31 March 2011, MEDLINE (1950 to 31 March 2011),
      EMBASE (1980 to 31 March 2011) and CINAHL (1982 to 31 March 2011). SELECTION
      CRITERIA: Randomised controlled trials or quasi-randomised controlled studies
      evaluating the effects of prophylactic phototherapy for preterm or low birth
      weight infants. DATA COLLECTION AND ANALYSIS: Two authors independently obtained
      data from published articles. We performed fixed-effect meta-analysis for the
      outcomes: rate of exchange transfusion, cerebral palsy or other
      neurodevelopmental impairment, peak serum bilirubin level and all-cause
      mortality. MAIN RESULTS: Nine studies of 3449 participants were included. The
      rate of exchange transfusion was reduced in one study with liberal transfusion
      criteria (risk ratio (RR) 0.20; 95% confidence interval (CI) 0.13 to 0.31) but
      not in the other two more recent studies with stringent criteria (typical RR
      0.66; 95% CI 0.19 to 2.28). There was no statistically significant difference in
      the rate of cerebral palsy (typical RR 0.96; 95% CI 0.50 to 1.85; two studies,
      756 participants). However, one large study that reported on neurodevelopmental
      impairment (a composite outcome including cerebral palsy) found a slightly lower
      rate of neurodevelopmental impairment with prophylactic phototherapy (RR 0.85;
      95% CI 0.74 to 0.99; 1804 participants). The prophylactic phototherapy group had
      lower peak bilirubin levels (mean difference (MD) -2.73; 95% CI -2.89 to -2.57;
      six studies, 2319 participants) and had fewer neonates with peak unconjugated
      serum bilirubin levels > 10 mg/dl (typical RR 0.27; 95% CI 0.22 to 0.33; three
      studies, 1090 participants) or peak unconjugated serum bilirubin levels > 15
      mg/dl (typical RR 0.13; 95% CI 0.07 to 0.23; four studies, 1116 participants).
      There was no statistically significant difference in the rate of all-cause
      mortality between the two groups (typical RR 1.08; 95% CI 0.93 to 1.26; four
      studies, 3044 participants). AUTHORS' CONCLUSIONS: Prophylactic phototherapy
      helps to maintain a lower serum bilirubin concentration and may have an effect on
      the rate of exchange transfusion and the risk of neurodevelopmental impairment.
      However, further well-designed studies are needed to determine the efficacy and
      safety of prophylactic phototherapy on long-term outcomes including
      neurodevelopmental outcomes.

PMID- 23878130
TI  - Prostate cancer invasion and metastasis: insights from mining genomic data.
AB  - Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men in
      the Western world and the second leading cause of cancer-related deaths among men
      worldwide. Although most cancers have the potential to metastasize under
      appropriate conditions, PCa favors the skeleton as a primary site of metastasis,
      suggesting that the bone microenvironment is conducive to its growth. PCa
      metastasis proceeds through a complex series of molecular events that include
      angiogenesis at the site of the original tumor, local migration within the
      primary site, intravasation into the blood stream, survival within the
      circulation, extravasation of the tumor cells to the target organ and
      colonization of those cells within the new site. In turn, each one of these steps
      involves a complicated chain of events that utilize multiple protein-protein
      interactions, protein signaling cascades and transcriptional changes. Despite the
      urgent need to improve current biomarkers for diagnosis, prognosis and drug
      resistance, advances have been slow. Global gene expression methods such as gene
      microarrays and RNA sequencing enable the study of thousands of genes
      simultaneously and allow scientists to examine molecular pathways of cancer
      pathogenesis. In this review, we summarize the current literature that explored
      high-throughput transcriptome analysis toward the advancement of biomarker
      discovery for PCa. Novel biomarkers are strongly needed to enable more accurate
      detection of PCa, improve prediction of tumor aggressiveness and facilitate the
      discovery of new therapeutic targets for tailored medicine. Promising molecular
      markers identified from gene expression profiling studies include HPN, CLU1, WT1,
      WNT5A, AURKA and SPARC. 

PMID- 23878132
TI  - Long-term outcome of scleral-fixated intraocular lens implantation.
AB  - PURPOSE: Implantation of a scleral-fixated intraocular lens (SFIOL) for the
      surgical management of aphakia in the absence of capsular support is a safe
      procedure with a low risk of complications in the early postoperative period.
      However, data on long-term functional outcome are limited. The purpose of this
      study is to assess the long-term outcome and complication profile of SFIOL
      implantation in a cohort of Chinese patients. METHODS: All patients who had
      undergone primary or secondary SFIOL implantation between 1997 and 2008 were
      retrospectively reviewed for visual outcomes and complications. Patients'
      demographic data and information on baseline preoperative visual acuity,
      indication for surgery, postoperative complications, latest postoperative visual
      acuity and indication for any subsequent surgical procedures were collected and
      analysed. RESULTS: 104 eyes of 99 patients (51 males and 48 females) were
      identified. Mean age at surgery was 67.1 +/- 13 years (range 32-88 years), with a
      mean follow-up of 73.4 +/- 43 months (range 12-180 months). 72% of patients had
      unchanged or improved final postoperative visual acuity. 25 of 104 eyes (24.0%)
      had postoperative complications, with suture-related complications being the most
      common. 13 eyes (12.5%) required further procedures for postoperative
      complications. Suture breakage leading to lens subluxation occurred in two eyes
      (1.9%). CONCLUSIONS: SFIOL implantation is valuable for the management of aphakia
      in the absence of capsular support, and our visual outcomes and complication
      rates are comparable to other case series. The long-term outcomes and safety
      profile are favourable, but potential long-term suture-related problems should be
      discussed with the patients before surgery.

PMID- 23878131
TI  - Transcription factor interplay in T helper cell differentiation.
AB  - The differentiation of CD4 helper T cells into specialized effector lineages has
      provided a powerful model for understanding immune cell differentiation. Distinct
      lineages have been defined by differential expression of signature cytokines and
      the lineage-specifying transcription factors necessary and sufficient for their
      production. The traditional paradigm of differentiation towards Th1 and Th2
      subtypes driven by T-bet and GATA3, respectively, has been extended to
      incorporate additional T cell lineages and transcriptional regulators.
      Technological advances have expanded our view of these lineage-specifying
      transcription factors to the whole genome and revealed unexpected interplay
      between them. From these data, it is becoming clear that lineage specification is
      more complex and plastic than previous models might have suggested. Here, we
      present an overview of the different forms of transcription factor interplay that
      have been identified and how T cell phenotypes arise as a product of this
      interplay within complex regulatory networks. We also suggest experimental
      strategies that will provide further insight into the mechanisms that underlie T
      cell lineage specification and plasticity. 

PMID- 23878133
TI  - Clinical characteristics and treatment of 22 eyes of morning glory syndrome
      associated with persistent hyperplastic primary vitreous.
AB  - PURPOSE: To describe the clinical manifestations and treatment outcomes in a
      retrospective case series of morning glory syndrome (MGS) associated with
      persistent hyperplastic primary vitreous (PHPV). METHODS: The medical records of
      85 eyes/74 patients referred for ophthalmology consultation diagnosed as MGS in
      our clinic were reviewed retrospectively. All patients underwent thorough
      ophthalmological examinations. 22 eyes of 19 patients diagnosed as having MGS
      associated with PHPV were included, accounting for 25.88% of all the MGS eyes.
      Clinical manifestations and management of these patients were documented.
      RESULTS: 15 patients (78.95%) were younger than 1 year old at the first
      diagnosis. Six eyes were associated with microphthalmia. 19 of 22 eyes (86.36%)
      had complications, including cataract (10 eyes), secondary glaucoma (8 eyes),
      corneal leucoma or oedema (8 eyes), retinal detachment (8 eyes), strabismus (3
      eyes) and nystagmus (2 eyes). Treatment methods varied depending on the severity
      of the complications. Nine eyes with secondary glaucoma or cataract got
      lensectomy; three eyes underwent combined vitrectomy and lensectomy. Eight
      patients underwent cranial MRI/MR angiography or CT examination. Widened cerebral
      fissures of bilateral temporal lobes, abnormal dilated branch of middle cerebral
      artery in the left hemisphere and abnormal signal in the grey matter of frontal
      and occipital lobes were revealed respectively in three patients. CONCLUSIONS:
      Our study revealed the coexistence of PHPV in a significant percentage of
      patients with MGS, suggesting a potential common genetic link. Compared with MGS
      and PHPV alone, the combination of the two conditions manifested with higher
      incidence and more severe complications in younger patients. Close follow-up was
      recommended. Lensectomy and vitrectomy were beneficial in the management of the
      complications.

PMID- 23878134
TI  - Acanthamoeba keratitis: study of the 5-year incidence in Israel.
AB  - BACKGROUND: Acanthamoeba keratitis (AK) is not a notifiable disease in Israel, so
      there are no accurate incidence rates for this condition in Israel. The aim of
      this study was to estimate the incidence of AK in Israel for the years 2008-2012.
      METHODS: We distributed a survey questionnaire to laboratory managers in Israel.
      The laboratories were affiliated to medical institutes that either provided
      ophthalmology services or served community ophthalmology clinics. Our
      questionnaire requested survey respondents to provide information regarding the
      methods used to diagnose AK, and the number of positive and negative cultures for
      Acanthamoebae species performed for each of the years from 2008 to 2012. RESULTS:
      Six laboratories used non-nutrient agar with Escherichia coli as the culture
      medium, one used calcofluor-white staining with fluorescent microscopy, and two
      used PCR for diagnosing AK. Twenty-three AK cases were identified, to give an
      estimated incidence of 1/1 668 552. CONCLUSIONS: AK is mostly attributable to the
      use of contact lenses. As contact lenses are popular in Israel, we expected a
      higher incidence rate. A lower than expected incidence rate may indicate
      insufficient awareness of AK in Israel.

PMID- 23878135
TI  - Cytokine profiling reveals decreased serum levels of CCL2 in active ocular
      toxoplasmosis.
AB  - BACKGROUND: Toxoplasma gondii infection is an important cause of ocular disease.
      Although parasite-mediated host cell lysis is probably the principal cause of
      tissue destruction in immunodeficiency states, hypersensitivity and inflammatory
      responses may underlie severe disease in otherwise immunocompetent individuals.
      The purpose of the current investigation was to study the cytokine profiles in
      serum from patients with ocular toxoplasmosis and to compare them with those
      obtained from healthy control subjects. METHODS: Using a multiplex assay, we
      determined the serum concentration of granulocyte colony-stimulating factor
      (GCSF), interferon gamma (IFNgamma), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL
      10, chemokine (C-C motif) ligand 2 (CCL2) and tumour necrosis factor alpha
      (TNFalpha) in patients with inactive ocular toxoplasmosis (n=48), active ocular
      toxoplasmosis (n=21), and an age-matched and sex-matched healthy control group
      (n=25). In a subgroup of 17 patients with active disease, a second serum sample
      was obtained when the disease was inactive. Cytokine profiles were correlated
      with disease activity, severity and visual outcome. RESULTS: Levels of CCL2 were
      significantly reduced in patients with active ocular toxoplasmosis compared to
      the control group (564 +/- 42 pg/mL vs 455 +/- 35 pg/mL, p<0.05). Moreover, CCL2
      levels were significantly lower during active ocular toxoplasmosis compared to
      inactive disease (569 +/- 32 pg/mL vs 433 +/- 32 pg/mL, p<0.01). GCSF and
      TNFalpha were elevated in patients with toxoplasmosis with poor visual outcome.
      No significant correlations were found with specific cytokine profiles and
      disease severity. CONCLUSIONS: Decreased serum levels of CCL2 may be associated
      with active ocular toxoplasmosis and could therefore serve as a marker of disease
      activity.

PMID- 23878139
TI  - A novel role for C3 in antibody-induced red blood cell clearance and antigen
      modulation.
AB  - Hemolytic transfusion reactions (HTRs) due to incompatible red blood cell (RBC)
      transfusions are a leading cause of transfusion associated death. Although many
      transfused incompatible RBCs are cleared, some remain in circulation despite the
      presence of RBC-specific antibodies, potentially due to "antigen modulation."
      With a goal of better understanding incompatible RBC clearance, we generated a
      murine model with RBC-specific expression of a clinically significant human
      antigen (KEL2) known to be involved in antigen modulation as well as in HTRs.
      Wild-type (WT) recipients transfused with transgenic KEL2 RBCs generated anti-KEL
      glycoprotein alloantibodies, which fixed complement, led to intravascular
      hemolysis, and resulted in decreased levels of KEL2 antigen detectable on cells
      remaining in circulation. Antigen modulation did not appear to solely reflect
      removal of RBCs with higher antigen expression, because cells continued to
      display antigen modulation in the absence of significant clearance. Recipients
      genetically lacking complement exhibited lesser degrees of incompatible RBC
      clearance and antigen modulation in comparison with WT or FcgammaR knock-out (KO)
      animals, suggesting a role for complement in RBC clearance. In summary, this HTR
      model may serve as a platform to test strategies to downmodulate antigen and
      inhibit incompatible RBC clearance, thus potentially mitigating transfusion
      dangers.

PMID- 23878140
TI  - Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor
      leukemia.
AB  - The t(8;21) and inv(16)/t(16;16) rearrangements affecting the core-binding
      factors RUNX1 and CBFB, respectively, are found in 15% to 20% of adult de novo
      acute myeloid leukemia (AML) cases and are associated with a favorable prognosis.
      Since the expression of the fusion genes CBFB/MYH11 or RUNX1/RUNX1T1 alone is not
      sufficient to cause leukemia, we performed exome sequencing of an AML sample with
      an inv(16) to identify mutations, which may collaborate with the CBFB/MYH11
      fusion during leukemogenesis. We discovered an N676K mutation in the adenosine
      triphosphate (ATP)-binding domain (tyrosine kinase domain 1 [TKD1]) of the fms
      related tyrosine kinase 3 (FLT3) gene. In a cohort of 84 de novo AML patients
      with a CBFB/MYH11 rearrangement and in 36 patients with a RUNX1/RUNX1T1
      rearrangement, the FLT3 N676K mutation was identified in 5 and 1 patients,
      respectively (5 [6%] of 84; 1 [3%] of 36). The FLT3-N676K mutant alone leads to
      factor-independent growth in Ba/F3 cells and, together with a concurrent FLT3-ITD
      (internal tandem duplication), confers resistance to the FLT3 protein tyrosine
      kinase inhibitors (PTKIs) PKC412 and AC220. Gene expression analysis of AML
      patients with CBFB/MYH11 rearrangement and FLT3 N676K mutation showed a trend
      toward a specific expression profile. Ours is the first report of recurring FLT3
      N676 mutations in core-binding factor (CBF) leukemias and suggests a defined
      subgroup of CBF leukemias.

PMID- 23878141
TI  - Treatment of acquired von Willebrand syndrome in childhood.
AB  - A 3-1/2-year-old male with no personal or family history of bleeding disorders
      presented with abdominal distension, epistaxis, and anemia (hemoglobin 8.2 g/dL).
      A magnetic resonance imaging scan of the abdomen demonstrated a mass arising from
      the left kidney. Preoperative laboratory studies revealed a prolonged activated
      partial thromboplastin time of 49.2 seconds, a normal prothrombin time of 12.4
      seconds, and a platelet count of 230, 000/MUL. Further testing revealed factor
      VIII (FVIII) activity of 16%, factor IX (FIX) activity of 74%, von Willebrand
      factor (VWF) activity of 12%, VWF antigen activity of 31%, and decreased high
      molecular-weight VWF multimers consistent with acquired von Willebrand syndrome
      (AVWS). What is the best treatment for this child?

PMID- 23878142
TI  - C3a modulates IL-1beta secretion in human monocytes by regulating ATP efflux and
      subsequent NLRP3 inflammasome activation.
AB  - Interleukin-1beta (IL-1beta) is a proinflammatory cytokine and a therapeutic
      target in several chronic autoimmune states. Monocytes and macrophages are the
      major sources of IL-1beta. IL-1beta production by these cells requires Toll-like
      receptor (TLR) and adenosine triphosphate (ATP)-mediated P2X purinoceptor 7
      (P2X7) signals, which together activate the inflammasome. However, how TLR
      signals and ATP availability are regulated during monocyte activation is unclear
      and the involvement of another danger signal system has been proposed. Here, we
      demonstrate that both lipopolysaccharide (LPS) and the anaphylatoxin C3a are
      needed for IL-1beta production in human macrophages and dendritic cells, while in
      monocytes, C3a enhanced the secretion of LPS-induced IL-1beta. C3a and LPS
      stimulated monocytes increased T helper 17 (Th17) cell induction in vitro, and
      human rejecting, but not nonrejecting, kidney transplant biopsies were
      characterized by local generation of C3a and monocyte and Th17 cell infiltration.
      Mechanistically, C3a drives IL-1beta production in monocytes by controlling the
      release of intracellular ATP into the extracellular space via regulation of as
      yet unidentified ATP-releasing channels in an extracellular signal-regulated
      kinase 1/2-dependent fashion. These data define a novel function for complement
      in inflammasome activation in monocytes and suggest that C3aR-mediated signaling
      is a vital component of the IL-1beta-Th17 axis. 

PMID- 23878144
TI  - Bridging intimate partner violence and the human brain: a literature review.
AB  - Past studies mainly focused on the physical and structural brain injuries in
      women survivors with a history of intimate partner violence (IPV), but little
      attention has been given to the biological impact and cognitive dysfunction
      resulting from such psychological stress. In this article, we aim to establish
      the connection between IPV and the brain by reviewing current literature
      examining (1) the biological mechanisms linking IPV, stress, and the brain; (2)
      the functional and anatomical considerations of the brain in abused women; and
      (3) the abused women's behavioral responses to IPV, including fear, pain, and
      emotion regulation, by utilizing functional neuroimaging. The major significance
      of this study is in highlighting the need to advance beyond self-reports and to
      obtain scientific evidence of the neurological impact and cognitive dysfunction
      in abused women with a history of IPV, an area in which current literature
      remains at a descriptive level. 

PMID- 23878143
TI  - The major histocompatibility complex: a model for understanding graft-versus-host
      disease.
AB  - Acute graft-versus-host disease (GVHD) afflicts as much as 80% of all patients
      who receive an unrelated donor hematopoietic cell transplant (HCT) for the
      treatment of blood disorders, even with optimal donor HLA matching and use of
      prophylactic immunosuppressive agents. Of patients who develop acute GVHD, many
      are at risk for chronic GVHD and bear the burden of considerable morbidity and
      lowered quality of life years after transplantation. The immunogenetic basis of
      GVHD has been the subject of intensive investigation, with the classic HLA
      genetic loci being the best-characterized determinants. Recent information on the
      major histocompatibility complex (MHC) region of chromosome 6 as an important
      source of untyped genetic variation has shed light on novel GVHD determinants.
      These data open new paradigms for understanding the genetic basis of GVHD. 

PMID- 23878145
TI  - The role of trauma symptoms in nonsuicidal self-injury.
AB  - Reports of traumatic events by individuals who engage in nonsuicidal self-injury
      (NSSI) are common; yet, evidence for the relation between traumatic events and
      NSSI is inconclusive. This review explores the thesis that trauma symptoms,
      rather than the experience of a traumatic event per se, underlie this relation,
      specifically suggesting that trauma symptoms might serve as a mediator. The
      literature indicates that self-injury plays an important functional role in
      coping with trauma symptoms such that self-injury can provide an escape from
      intrusive thoughts and aversive emotional states, as well as end dissociation and
      periods of numbness through the generation of feelings. Additionally, trauma
      symptoms have been shown to mediate the relation between the occurrence of
      traumatic events and NSSI. Taken together, trauma symptoms may play an important
      role in the development and maintenance of NSSI. The review concludes with
      treatment implications and future directions for research. 

PMID- 23878147
TI  - Academy on Violence and Abuse: highlights of proceedings from the 2011
      conference, "toward a new understanding".
AB  - In April 2011, the Academy on Violence Abuse (http://www.avahealth.org/) convened
      a network of experts for its second annual conference, "Developing the Science of
      Violence and Abuse: Toward a New Understanding." The conference served as a forum
      for highlighting the growing body of research regarding the biological
      consequences and adverse health consequences of abuse. In doing so, it
      underscored an important scientific premise: By evaluating the impact of violence
      and abuse from birth to death, one can better evaluate the social, behavioral,
      psychological, and biological context and pathways that result in the morbidity,
      mortality, and quality of life of all affected individuals and communities. In
      this article, we summarize content presented by the conference's keynote speakers
      and provide citations that speakers have submitted to support their statements. 

PMID- 23878146
TI  - Intimate partner violence victimization and cigarette smoking: a meta-analytic
      review.
AB  - The current meta-analytic review represents the first comprehensive empirical
      evaluation of the strength of the relationship between intimate partner violence
      (IPV) victimization and cigarette smoking. Thirty-nine effect sizes, drawn from
      31 peer-reviewed publications, determined the existence of a small to medium
      composite effect size for the victimization-smoking relationship (d = .41, 95%
      confidence interval = [.35, .47]). Results indicate that victims of IPV are at
      greater smoking risk than nonvictims. Subsequent moderator analyses indicated
      that the association between victimization and smoking is moderately stronger
      among pregnant compared to nonpregnant victims. The strength of the victimization
      smoking relationship did not differ by relationship type or ethnicity. More
      research is needed on the smoking behavior of male victims, victims of
      psychological violence, and victims who identify as Latino/Latina. It would be
      useful for professionals working with IPV victims to assess for smoking and
      incorporate smoking prevention and cessation skills in intervention settings. 

PMID- 23878148
TI  - A review on the prevalence and measurement of elder abuse in the community.
AB  - OBJECTIVES: Aging is a rising phenomenon globally and elder abuse is becoming
      increasingly recognized as a health and social problem. This review aimed to
      identify the prevalence of elder abuse in community settings, and discuss issues
      regarding measurement tools and strategies to measure elderly abuse by
      systematically reviewing all community-based studies conducted worldwide. METHOD:
      Articles on elder abuse from 1990 to 2011 were reviewed. A total of 1,832
      articles referring to elders residing at home either in their own or at
      relatives' houses were searched via CINAHL and MEDLINE electronic databases, in
      addition to a hand search of the latest articles in geriatric textbooks and
      screening references, choosing a total of 26 articles for review. RESULTS:
      Highest prevalence was reported in developed countries, with Spain having 44.6%
      overall prevalence of suspicion of abuse and developing countries exhibiting
      lower estimates, from 13.5% to 28.8%. Physical abuse was among the least
      encountered, with psychological abuse and financial exploitation being the most
      common types of maltreatment reported. To date, there is no single gold standard
      test to ascertain abuse, with numerous tools and different methods employed in
      various studies, coupled with varying definitions of thresholds for age.
      CONCLUSION: Current evidences show that elder abuse is a common problem in both
      developed and developing countries. It is important that social, health care, and
      legal systems take these findings into consideration in screening for abuse or
      reforming existing services to protect the health and welfare of the elderly.

PMID- 23878150
TI  - Current practice for diagnosis and management of silent atrial fibrillation:
      results of the European Heart Rhythm Association survey.
AB  - Although it is well known that silent atrial fibrillation (AF) is associated with
      morbidity and mortality rates similar to those of symptomatic AF, no specific
      strategy for screening and management of this form of AF has been advocated. The
      purpose of this survey was to identify current practices for the diagnosis and
      management of silent AF. This survey is based on an electronic questionnaire sent
      to the European Heart Rhythm Association Research Network partners. Responses
      were received from 33 centres in 16 countries. The preferred screening methods
      for silent AF in patients with rhythm control by pharmacological therapy was 12
      lead electrocardiogram (ECG) at outpatient visits (31.3%) and periodical 24 h
      Holter ECG recordings (34.4%), while after pulmonary vein isolation the
      corresponding figures were 6.3 and 65.6%, respectively. No consensus has been
      reached concerning the therapeutic approach for such patients. Most responders
      preferred rate control over rhythm control in patients with silent AF, although
      some favoured pulmonary vein isolation in young patients. However, oral
      anticoagulant therapy in patients at high thromboembolic risk was considered
      mandatory by most, provided that at least one episode of silent AF was
      documented, without recommending further investigations. The results of this
      survey have confirmed that there is currently no consensus regarding the
      screening and management of patients with silent AF and that clinical practice is
      not always consistent with the few existing evidence-based recommendations. 

PMID- 23878151
TI  - Investigating stable chest pain of suspected cardiac origin.

PMID- 23878152
TI  - High sensitivity cardiac troponin in patients with chest pain.

PMID- 23878153
TI  - Consumer demand drives boom in urgent care centers, study finds.

PMID- 23878154
TI  - Plain packaging seems to increase thoughts about quitting smoking.

PMID- 23878155
TI  - Dependence of high deficit hospitals on bailouts is unsustainable, audit office
      finds.

PMID- 23878156
TI  - Honey bee protein atlas at organ-level resolution.
AB  - Genome sequencing has provided us with gene lists but cannot tell us where and
      how their encoded products work together to support life. Complex organisms rely
      on differential expression of subsets of genes/proteins in organs and tissues,
      and, in concert, evolved to their present state as they function together to
      improve an organism's overall reproductive fitness. Proteomics studies of
      individual organs help us understand their basic functions, but this reductionist
      approach misses the larger context of the whole organism. This problem could be
      circumvented if all the organs in an organism were comprehensively studied by the
      same methodology and analyzed together. Using honey bees (Apis mellifera L.) as a
      model system, we report here an initial whole proteome of a complex organism,
      measuring 29 different organ/tissue types among the three honey bee castes:
      queen, drone, and worker. The data reveal that, e.g., workers have a heightened
      capacity to deal with environmental toxins and queens have a far more robust
      pheromone detection system than their nestmates. The data also suggest that
      workers altruistically sacrifice not only their own reproductive capacity but
      also their immune potential in favor of their queen. Finally, organ-level
      resolution of protein expression offers a systematic insight into how organs may
      have developed. 

PMID- 23878159
TI  - National BTS bronchiectasis audit 2012: is the quality standard being adhered to
      in adult secondary care?
AB  - A significant step towards improving care of patients with non-cystic fibrosis
      bronchiectasis was the creation of the British Thoracic Society (BTS) national
      guidelines and the quality standard. A BTS bronchiectasis audit was conducted
      between 1 October and 30 November 2012, in adult patients with bronchiectasis
      attending secondary care, against the BTS quality standard. Ninety-eight
      institutions took part, submitting a total of 3147 patient records. The audit
      highlighted the variable adoption of the quality standard. It will allow the host
      institutions to benchmark against UK figures and drive quality improvement
      programmes to promote the quality standard and improve patient care. 

PMID- 23878158
TI  - Directed shotgun proteomics guided by saturated RNA-seq identifies a complete
      expressed prokaryotic proteome.
AB  - Prokaryotes, due to their moderate complexity, are particularly amenable to the
      comprehensive identification of the protein repertoire expressed under different
      conditions. We applied a generic strategy to identify a complete expressed
      prokaryotic proteome, which is based on the analysis of RNA and proteins
      extracted from matched samples. Saturated transcriptome profiling by RNA-seq
      provided an endpoint estimate of the protein-coding genes expressed under two
      conditions which mimic the interaction of Bartonella henselae with its mammalian
      host. Directed shotgun proteomics experiments were carried out on four
      subcellular fractions. By specifically targeting proteins which are short, basic,
      low abundant, and membrane localized, we could eliminate their initial
      underrepresentation compared to the estimated endpoint. A total of 1250 proteins
      were identified with an estimated false discovery rate below 1%. This represents
      85% of all distinct annotated proteins and ~90% of the expressed protein-coding
      genes. Genes that were detected at the transcript but not protein level, were
      found to be highly enriched in several genomic islands. Furthermore, genes that
      lacked an ortholog and a functional annotation were not detected at the protein
      level; these may represent examples of overprediction in genome annotations. A
      dramatic membrane proteome reorganization was observed, including differential
      regulation of autotransporters, adhesins, and hemin binding proteins.
      Particularly noteworthy was the complete membrane proteome coverage, which
      included expression of all members of the VirB/D4 type IV secretion system, a key
      virulence factor. 

PMID- 23878160
TI  - On-treatment platelet reactivity in patients with chronic obstructive pulmonary
      disease undergoing percutaneous coronary intervention.
AB  - Patients with chronic obstructive pulmonary disease (COPD) show a poor prognosis
      after myocardial infarction (MI) and percutaneous coronary intervention (PCI). We
      evaluated on-treatment platelet reactivity (PR) and several gene polymorphisms
      related to PR in 130 patients undergoing PCI with and without COPD. Those with
      concomitant COPD showed higher on-treatment PR values both at the time of PCI and
      1 month after. This finding may contribute to explain the poor prognosis of COPD
      patients after MI and PCI. 

PMID- 23878162
TI  - Two CDC reports look at regional, racial, and sex disparities in US health.

PMID- 23878163
TI  - Junior doctor's conviction for involuntary manslaughter raises concern over
      medical training.

PMID- 23878161
TI  - The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133
      expression in early stage non-small cell lung cancer.
AB  - BACKGROUND: Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been
      functionally associated with a stem cell phenotype in normal and malignant cells.
      The prevalence of such cells in solid tumours should therefore correlate with
      recurrence and/or metastasis following definitive surgical resection. The aim of
      this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in
      surgically resected, early stage non-small cell lung cancer (NSCLC). METHODS: A
      retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with
      pathologic stage I NSCLC was performed using immunohistochemistry. The
      association between the expression of both markers and survival was determined.
      RESULTS: We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A
      and 61 stage 1B patients, analysed at a median of 5-years follow-up.
      Overexpression of ALDH1A1 and CD133, detected in 68.7% and 50.7% of primary
      tumours, respectively, was an independent prognostic indicator for overall
      survival by multivariable Cox proportional hazard model (p=0.017 and 0.039,
      respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor
      recurrence-free survival (p=0.025). When categorised into three groups according
      to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and
      CD133 belonged to the group with the shortest recurrence-free and overall
      survival (p=0.015 and 0.017, respectively). CONCLUSIONS: Expression of ALDH1A1
      and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with
      poor survival in early-stage NSCLC following surgical resection. These data are
      consistent with the hypothesis that expression of stem cell markers correlates
      with recurrence as an indirect measure of self-renewal capacity.

PMID- 23878164
TI  - Drive to boost health checks in England is criticised.

PMID- 23878157
TI  - Coelacanth genomes reveal signatures for evolutionary transition from water to
      land.
AB  - Coelacanths are known as "living fossils," as they show remarkable morphological
      resemblance to the fossil record and belong to the most primitive lineage of
      living Sarcopterygii (lobe-finned fishes and tetrapods). Coelacanths may be key
      to elucidating the tempo and mode of evolution from fish to tetrapods. Here, we
      report the genome sequences of five coelacanths, including four Latimeria
      chalumnae individuals (three specimens from Tanzania and one from Comoros) and
      one L. menadoensis individual from Indonesia. These sequences cover two African
      breeding populations and two known extant coelacanth species. The genome is ~2.74
      Gbp and contains a high proportion (~60%) of repetitive elements. The genetic
      diversity among the individuals was extremely low, suggesting a small population
      size and/or a slow rate of evolution. We found a substantial number of genes that
      encode olfactory and pheromone receptors with features characteristic of tetrapod
      receptors for the detection of airborne ligands. We also found that limb
      enhancers of bmp7 and gli3, both of which are essential for limb formation, are
      conserved between coelacanth and tetrapods, but not ray-finned fishes. We expect
      that some tetrapod-like genes may have existed early in the evolution of
      primitive Sarcopterygii and were later co-opted to adapt to terrestrial
      environments. These coelacanth genomes will provide a cornerstone for studies to
      elucidate how ancestral aquatic vertebrates evolved into terrestrial animals. 

PMID- 23878165
TI  - Functional bowel symptoms in quiescent inflammatory bowel diseases: role of
      epithelial barrier disruption and low-grade inflammation.
AB  - OBJECTIVE: To determine the role of colonic barrier defects and low-grade
      inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent
      inflammatory bowel disease (IBD). DESIGN: Caecal biopsies were collected from 51
      IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC))
      patients and 27 controls. IBS was assessed using the Rome III criteria and the
      IBS severity score. Epithelial barrier integrity was evaluated by determining the
      paracellular permeability of biopsies mounted in Ussing chambers and the mRNA
      expression of tight junction proteins (ZO-1, alpha-catenin and occludin). Low
      grade inflammation was evaluated by counting cells, including intraepithelial
      lymphocytes (IELs), eosinophils and mast cells, and by determining the mRNA and
      protein expression of tumour necrosis factor (TNF)-alpha in biopsies and culture
      supernatants. RESULTS: IBS-like symptoms were present in 35.4 and 38% of CD and
      UC patients, respectively. Paracellular permeability was significantly increased
      in both quiescent IBD with IBS-like symptoms and IBS compared with quiescent IBD
      without IBS-like symptoms (p<0.01, respectively) or controls (p<0.01,
      respectively). Significantly lower expression of ZO-1 and alpha-catenin was
      detected in IBS and quiescent IBD with IBS-like symptoms. IELs and TNF-alpha were
      significantly increased in quiescent IBD with IBS-like symptoms, but not in IBS.
      CONCLUSIONS: In quiescent IBD, IBS-like symptoms related to persistent
      subclinical inflammation associated with increased colonic paracellular
      permeability. A persistent increase in TNF-alpha in colonic mucosa may contribute
      to the epithelial barrier defects associated with abdominal pain in quiescent
      IBD, but not in IBS. Optimisation of anti-inflammatory therapy may be considered
      in quiescent IBD with IBS-like symptoms.

PMID- 23878166
TI  - Editing liver tumours.

PMID- 23878167
TI  - Individualised therapy is more cost-effective than dose intensification in
      patients with Crohn's disease who lose response to anti-TNF treatment: a
      randomised, controlled trial.
AB  - OBJECTIVE: Although the reasons for secondary loss of response to infliximab
      (IFX) maintenance therapy in Crohn's disease vary, dose intensification is
      usually recommended. This study investigated the cost-effectiveness of
      interventions defined by an algorithm designed to identify specific reasons for
      therapeutic failure. DESIGN: Randomised, controlled, single-blind, multicentre
      study. 69 patients with secondary IFX failure were randomised to IFX dose
      intensification (5 mg/kg every 4 weeks) (n=36) or interventions based on serum
      IFX and IFX antibody levels using the proposed algorithm (n=33). Predefined co
      primary end points at week 12 were proportion of patients responding (Crohn's
      Disease Activity Index (CDAI) decrease >= 70, or >= 50% reduction in active
      fistulas) and accumulated costs related to treatment of Crohn's disease,
      expressed as mean cost per patient, based on the Danish National Patient Registry
      for all hospitalisation and outpatient costs in the Danish healthcare sector.
      RESULTS: Costs for intention-to-treat patients were substantially lower (34%) for
      those treated in accordance with the algorithm than by IFX dose intensification:
      ? 6038 vs ? 9178, p<0.001. However, disease control, as judged by response rates,
      was similar: 58% and 53%, respectively, p=0.81; difference 5% (-19% to 28%). For
      per-protocol patients, treatment costs were even lower (56%) in the algorithm
      treated group (? 4062 vs ? 9178, p<0.001) and with similar response rates (47% vs
      53%, p=0.78; difference -5% (-33% to 22%)). CONCLUSIONS: Treatment of secondary
      IFX failure using an algorithm based on combined IFX and IFX antibody
      measurements significantly reduces average treatment costs per patient compared
      with routine IFX dose escalation and without any apparent negative effect on
      clinical efficacy. TRIAL REGISTRATION NO: NCT00851565.

PMID- 23878168
TI  - Which smoking cessation aids are proven effective according to smokers who want
      to quit smoking? A report from the Netherlands.

PMID- 23878169
TI  - Growth of mature boreal Norway spruce was not affected by elevated [CO(2)] and/or
      air temperature unless nutrient availability was improved.
AB  - The growth responses of mature Norway spruce (Picea abies (L.) Karst.) trees
      exposed to elevated [CO(2)] (CE; 670-700 ppm) and long-term optimized nutrient
      availability or elevated air temperature (TE; +/-3.9  degrees C) were studied in
      situ in northern Sweden in two 3 year field experiments using 12 whole-tree
      chambers in ca. 40-year-old forest. The first experiment (Exp. I) studied the
      interactions between CE and nutrient availability and the second (Exp. II)
      between CE and TE. It should be noted that only air temperature was elevated in
      Exp. II, while soil temperature was maintained close to ambient. In Exp. I, CE
      significantly increased the mean annual height increment, stem volume and biomass
      increment during the treatment period (25, 28, and 22%, respectively) when
      nutrients were supplied. There was, however, no significant positive CE effect
      found at the low natural nutrient availability. In Exp. II, which was conducted
      at the natural site fertility, neither CE nor TE significantly affected height or
      stem increment. It is concluded that the low nutrient availability (mainly
      nitrogen) in the boreal forests is likely to restrict their response to the
      continuous rise in [CO(2)] and/or TE.

PMID- 23878170
TI  - Predicting thresholds of drought-induced mortality in woody plant species.

PMID- 23878171
TI  - Association between childhood adversities and adulthood depressive symptoms in
      South Korea: results from a nationally representative longitudinal study.
AB  - OBJECTIVE: To examine how childhood adversity (ie, parental death, parental
      divorce, suspension of school education due to financial strain or being raised
      in a relative's house due to financial strain) is associated with prevalence and
      incidence of adulthood depressive symptoms and whether this association differs
      by gender and by age in South Korea. DESIGN: Prospective cohort design. SETTING:
      Nationally representative longitudinal survey in South Korea. PARTICIPANTS: 11
      526 participants in South Korea. OUTCOME MEASURE: Prevalence and incidence of
      adulthood depressive symptoms were assessed as a dichotomous variable using the
      Centers for Epidemiologic Studies Depression (CES-D) Scale in 2006 and 2007.
      RESULTS: In the prevalence analysis, each of the four childhood adversities was
      significantly associated with a higher prevalence of adulthood depressive
      symptoms. The higher incidence of depressive symptoms was associated with
      suspension of school education (OR 1.55, 95% CI 1.32 to 1.82) and parental
      divorce (OR 1.65, 95% CI 1.00 to 2.71). In the age-stratified analyses,
      prevalence of depressive symptoms was associated with all CAs across different
      adulthoods, except for parental divorce and late adulthood depressive symptoms.
      After being stratified by gender, the association was significant for parental
      divorce (OR 3.76, 95% CI 2.34 to 6.03) in the prevalence analysis and for being
      raised in a relative's house (OR 1.89, 95% CI 1.21 to 2.94) in the incidence
      analysis only among women. CONCLUSIONS: This study suggests that childhood
      adversity may increase prevalence and incidence of adulthood depressive symptoms,
      and the impact of parental divorce or being raised in a relative's house due to
      financial strain on adulthood depressive symptoms may differ by gender.

PMID- 23878172
TI  - The effectiveness of schemes that refine referrals between primary and secondary
      care--the UK experience with glaucoma referrals: the Health Innovation &
      Education Cluster (HIEC) Glaucoma Pathways Project.
AB  - OBJECTIVES: A comparison of glaucoma referral refinement schemes (GRRS) in the UK
      during a time period of considerable change in national policy and guidance.
      DESIGN: Retrospective multisite review. SETTING: The outcomes of clinical
      examinations by optometrists with a specialist interest in glaucoma (OSIs) were
      compared with optometrists with no specialist interest in glaucoma (non-OSIs).
      Data from Huntingdon and Nottingham assessed non-OSI findings, while Manchester
      and Gloucestershire reviewed OSI findings. PARTICIPANTS: 1086 patients. 434
      patients were from Huntingdon, 179 from Manchester, 204 from Gloucestershire and
      269 from Nottingham. RESULTS: The first-visit discharge rate (FVDR) for all time
      periods for OSIs was 14.1% compared with 36.1% from non-OSIs (difference 22%, CI
      16.9% to 26.7%; p<0.001). The FVDR increased after the April 2009 National
      Institute for Health and Clinical Excellence (NICE) glaucoma guidelines compared
      with pre-NICE, which was particularly evident when pre-NICE was compared with the
      current practice time period (OSIs 6.2-17.2%, difference 11%, CI -24.7% to 4.3%;
      p=0.18, non-OSIs 29.2-43.9%, difference 14.7%, CI -27.8% to -0.30%; p=0.03).
      Elevated intraocular pressure (IOP) was the commonest reason for referral for
      OSIs and non-OSIs, 28.7% and 36.1%, respectively, of total referrals. The
      proportion of referrals for elevated IOP increased from 10.9% pre-NICE to 28.0%
      post-NICE for OSIs, and from 19% to 45.1% for non-OSIs. CONCLUSIONS: In terms of
      'demand management', OSIs can reduce FVDR of patients reviewed in secondary care;
      however, in terms of 'patient safety' this study also shows that overemphasis on
      IOP as a criterion for referral is having an adverse effect on both the non-OSIs
      and indeed the OSIs ability to detect glaucomatous optic nerve features. It is
      recommended that referral letters from non-OSIs be stratified for risk, directing
      high-risk patients straight to secondary care, and low-risk patients to OSIs.

PMID- 23878173
TI  - Methods used to conduct and report Bayesian mixed treatment comparisons published
      in the medical literature: a systematic review.
AB  - OBJECTIVES: To identify published closed-loop Bayesian mixed treatment
      comparisons (MTCs) and to summarise characteristics regarding their conduct and
      reporting. DESIGN: Systematic review. METHODS: We searched multiple bibliographic
      databases (January 2006-31 July 2011) for full-text, English language
      publications of Bayesian MTCs comparing the effectiveness or safety of >=3
      interventions based on randomised controlled trials and having at least one
      closed loop. Methodological and reporting characteristics of MTCs were extracted
      in duplicate and summarised descriptively. RESULTS: We identified 34 Bayesian
      MTCs spanning 13 clinical areas. Publication of MTCs increased over the 5-year
      period; with 76.5% published during or after 2009. MTCs included a mean (+/-SD)
      of 35.9+/-30.1 trials (n=33 459+/-71 233 participants) and 8.5+/-4.3
      interventions (85.7% pharmacological). Non-informative and informative prior
      distributions were reported to be used in 44.1% and 8.8% of MTCs, respectively,
      with the remainder failing to specify the prior used. A random-effects model was
      used to analyse the networks of trials in 58.5% of MTCs, all using WinBUGS;
      however, code was infrequently provided (20.6%). More than two-thirds of MTCs
      (76.5%) also conducted traditional meta-analysis. Methods used to evaluate
      convergence, heterogeneity and inconsistency were infrequently reported, but from
      those providing detail, methods appeared varied. MTCs most often used a binary
      effect measure (85.3%) and ranking of interventions based on probability was
      common (61.8%), although rarely displayed in a figure (8.8% of MTCs). MTCs were
      published in 24 different journals with a mean impact factor of 9.20+/-8.71.
      While 70.8% of journals imposed limits on word counts and 45.8% limits on the
      number of tables/figures, online supplements/appendices were allowed in 79.2% of
      journals. Publication of closed-loop Bayesian MTCs is increasing in frequency,
      but details regarding their methodology are often poorly described. Efforts in
      clarifying the appropriate methods and reporting of Bayesian MTCs should be of
      priority.

PMID- 23878174
TI  - Introduction effects of the Australian plain packaging policy on adult smokers: a
      cross-sectional study.
AB  - OBJECTIVE: To determine whether smokers smoking from packs required under
      Australia's plain packaging law had different smoking beliefs and quitting
      thoughts, compared with those still smoking from branded packs. DESIGN: Cross
      sectional survey during the roll-out phase of the law, analysed by timing of
      survey. SETTING: Australian state of Victoria, November 2012. PARTICIPANTS: 536
      cigarette smokers with a usual brand, of whom 72.3% were smoking from a plain
      pack and 27.7% were smoking from a branded pack. PRIMARY OUTCOME MEASURES:
      Perceived quality and satisfaction of cigarettes compared with 1 year ago,
      frequency of thoughts of smoking harm, perceived exaggeration of harms, frequency
      of thoughts of quitting, quitting priority in life, intention to quit, approval
      of large graphic health warnings and plain packaging. RESULTS: Compared with
      branded pack smokers, those smoking from plain packs perceived their cigarettes
      to be lower in quality (adjusted OR (AdjOR)=1.66, p=0.045), tended to perceive
      their cigarettes as less satisfying than a year ago (AdjOR=1.70, p=0.052), were
      more likely to have thought about quitting at least once a day in the past week
      (AdjOR=1.81, p=0.013) and to rate quitting as a higher priority in their lives
      (F=13.11, df=1, p<0.001). Plain pack smokers were more likely to support the
      policy than branded pack smokers (AdjOR=1.51, p=0.049). Branded and plain pack
      smokers did not differ on measures of less immediate smoking intentions,
      frequency of thoughts about harms or perceived exaggeration of harms. Appeal
      outcomes, but not other outcomes, were sensitive to the extent of roll-out, with
      responses from branded pack smokers approaching those of plain pack smokers, once
      80% of survey respondents were smoking from plain packs 1-2 weeks before the
      December implementation date. CONCLUSIONS: The early indication is that plain
      packaging is associated with lower smoking appeal, more support for the policy
      and more urgency to quit among adult smokers.

PMID- 23878176
TI  - Widening clinical applications of the SYNTAX Score.
AB  - The SYNTAX Score (http://www.syntaxscore.com) has established itself as an
      anatomical based tool for objectively determining the complexity of coronary
      artery disease and guiding decision-making between coronary artery bypass graft
      (CABG) surgery and percutaneous coronary intervention (PCI). Since the landmark
      SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) Trial comparing CABG
      with PCI in patients with complex coronary artery disease (unprotected left main
      or de novo three vessel disease), numerous validation studies have confirmed the
      clinical validity of the SYNTAX Score for identifying higher-risk subjects and
      aiding decision-making between CABG and PCI in a broad range of patient types.
      The SYNTAX Score is now advocated in both the European and US revascularisation
      guidelines for decision-making between CABG and PCI as part of a SYNTAX-pioneered
      heart team approach. Since establishment of the SYNTAX Score, widening clinical
      applications of this clinical tool have emerged. The purpose of this review is to
      systematically examine the widening applications of tools based on the SYNTAX
      Score: (1) by improving the diagnostic accuracy of the SYNTAX Score by adding a
      functional assessment of lesions; (2) through amalgamation of the anatomical
      SYNTAX Score with clinical variables to enhance decision-making between CABG and
      PCI, culminating in the development and validation of the SYNTAX Score II, in
      which objective and tailored decisions can be made for the individual patient;
      (3) through assessment of completeness of revascularisation using the residual
      and post-CABG SYNTAX Scores for PCI and CABG patients, respectively. Finally, the
      future direction of the SYNTAX Score is covered through discussion of the ongoing
      development of a non-invasive, functional SYNTAX Score and review of current and
      planned clinical trials.

PMID- 23878177
TI  - Orthostatic hypotension and mortality risk: a meta-analysis of cohort studies.
AB  - CONTEXT: Orthostatic hypotension (OH) has been found to be related to increased
      risk of mortality, although results of previous cohort studies were not always
      consistent. OBJECTIVE: The aim of this meta-analysis was to investigate the
      association between OH and mortality risk. DATA SOURCE: Medline, Embase and
      references cited in related reviews and studies. STUDY SELECTION: Cohort studies
      evaluating the association between OH and mortality risk were identified. DATA
      EXTRACTION: Two investigators read all papers and extracted all relevant
      information. RESULTS: A total of 56 125 subjects with 11 580 mortality cases from
      nine cohorts were included in the meta-analysis. Pooled results indicated that
      the presence of OH at baseline was significantly associated with an increased
      risk of all-cause mortality (adjusted risk ratio (RR) = 1.40, p<0.001). Subgroup
      analysis suggested that the association between OH and all-cause mortality was
      less strong for the studies in which classic risk factors were adequately
      adjusted compared with those in which they were not adequately controlled. In
      addition, although our meta-analysis failed to reveal a significant association
      between OH and cardiovascular (CV) mortality (RR=1.20, p=0.47), we did find that
      subjects with OH had an increased risk of non-CV mortality (RR=1.18, p=0.05).
      CONCLUSIONS: The presence of OH is associated with a significantly increased risk
      of all-cause mortality, which may partially be mediated by classic risk factors.
      Further research is needed to determine whether the association between OH and
      mortality risk is causal.

PMID- 23878175
TI  - Safety and efficacy of dabigatran versus warfarin in patients undergoing catheter
      ablation of atrial fibrillation: a systematic review and meta-analysis.
AB  - BACKGROUND: Dabigatran etexilate, a new thrombin inhibitor, has been shown to be
      comparable to warfarin in patients with atrial fibrillation (AF). However, there
      is a limited body of evidence on the efficacy and safety of using dabigatran
      among patients undergoing AF catheter ablation. OBJECTIVE: A random effects meta
      analysis was performed of controlled trials comparing dabigatran and warfarin in
      paroxysmal/persistent AF patients undergoing catheter ablation. METHODS: Data
      sources included Medline, Embase, and Cochrane (from inception to April 2013).
      Three independent reviewers selected studies comparing warfarin to dabigatran.
      Descriptive and quantitative information was extracted from each selected study,
      regarding periprocedural all cause mortality, thromboembolic events and major
      bleeding, as well as modalities of periprocedural anticoagulation bridging.
      RESULTS: After a detailed screening of 228 search results, 14 studies were
      identified enrolling a total of 4782 patients (1823 treated with dabigatran and
      2959 with warfarin). No deaths were reported. No significant differences were
      found between patients treated with dabigatran and warfarin as regards
      thromboembolic events (0.55% dabigatran vs 0.17% warfarin; risk ratios (RR)=1.78,
      95% CI 0.66 to 4.80; p=0.26) and major bleeding (1.48% dabigatran vs 1.35%
      warfarin; RR=1.07, 95% CI 0.51 to 2.26; p=0.86). No difference was found between
      the 110 mg twice daily and 150 mg twice daily dabigatran dosages concerning major
      bleeding (0% vs 1.62%, respectively; RR=0.19, 95% CI 0.01 to 3.18; p=0.25) and
      thromboembolism (0% vs 0.40%, respectively; RR=0.72, 95% CI 0.04 to 12.98;
      p=0.82). CONCLUSIONS: In the specific setting of AF catheter ablation, this first
      pooled analysis suggests that patients treated with dabigatran have a similar
      incidence of thromboembolic events and major bleeding compared to warfarin, with
      low event rates overall.

PMID- 23878178
TI  - Starting statins for primary prevention of cardiovascular disease.

PMID- 23878179
TI  - An evaluation of novel, lower-cost molecular screening tests for human
      papillomavirus in rural China.
AB  - New, lower-cost tests that target high-risk human papillomavirus (HR-HPV) have
      been developed for cervical cancer screening in lower-resource settings but
      large, population-based screening studies are lacking. Women ages 25 to 65 years
      and living in rural China (n = 7,543) self-collected a cervicovaginal specimen,
      had 2 cervical specimens collected by a clinician, and underwent visual
      inspection after acetic acid (VIA). The self- and one clinician-collected
      specimens underwent HR-HPV DNA testing by careHPV (QIAGEN) and Hybrid Capture 2
      (HC2; QIAGEN) and the other clinician-collected specimen was tested for HPV16,
      18, and 45 E6 using OncoE6 (Arbor Vita Corporation). Women who screened positive
      for any test and a random sample of those negative on all tests underwent
      colposcopic evaluation. The percent test positive was 1.8% for HPV E6
      oncoprotein, between 14% and 18% for HR-HPV DNA testing, and 7.3% for VIA. The
      sensitivity for cervical intraepithelial neoplasia grade 3 or more severe
      (CIN3(+); n = 99) was 53.5% for OncoE6, 97.0% for both careHPV and HC2 testing of
      the clinician-collected specimen, 83.8% for careHPV testing and 90.9% for HC2
      testing of the self-collected specimen, and 50.5% for VIA. OncoE6 had the
      greatest positive predictive value (PPV), at 40.8% for CIN3(+), compared with the
      other tests, which had a PPV of less than 10%. OncoE6 tested 70.3% positive for
      HPV16, 18, or 45-positive CIN3(+) and tested negative for all HPV16-, 18-, or 45
      negative CIN3(+) (P < 0.0001). HPV E6 oncoprotein detection is useful for
      identifying women who have cervical precancer and cancer.

PMID- 23878180
TI  - Catastrophic payment for assisted reproduction techniques with conventional
      ovarian stimulation in the public health sector of South Africa: frequency and
      coping strategies.
AB  - STUDY QUESTION: How often does out-of-pocket payment (OPP) for assisted
      reproduction techniques (ART) with conventional ovarian stimulation result in
      catastrophic expenditure for households? SUMMARY ANSWER: Catastrophic cost was a
      frequent event affecting 51% of the poorest study participants and one in five
      couples in total. WHAT IS KNOWN ALREADY: There is increasing concern about
      catastrophic spending on health by households in low resource settings, but to
      date no study has evaluated OPP for ART. STUDY DESIGN, SIZE, DURATION: We
      conducted a prospective observational study comprising 135 couples undergoing ART
      between March 2009 and June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The
      study was set at an urban, level 3 referral hospital in the public and academic
      health sector of South Africa. At this institution ART is subsidized but requires
      co-payment by patients. Couples undergoing ART with conventional ovarian
      stimulation using GnRH analogs were recruited. A questionnaire capturing
      information on socioeconomic status, monthly household expenditure, OPP for the
      index ART cycle and financial coping strategies was administered. Households were
      categorized into tertiles according to socio-economic status. In addition to
      descriptive statistics, annualized OPP for ART services as a percentage of annual
      non-food household expenditure was calculated to estimate catastrophic health
      care expenditure. The Pearson chi(2) test and a logistic regression were used to
      identify factors related to incurring catastrophic spending. MAIN RESULTS AND THE
      ROLE OF CHANCE: In total, one in five couples (22%) incurred catastrophic
      expenditure (P < 0.01), defined as an OPP of >= 40% of annual non-food
      expenditure. Households used a range of coping strategies including reduced
      expenditure on items such as clothing and food, use of savings, borrowing money
      and taking on extra work. Differences were observed between the socio-economic
      tertiles: in the poorest tertile, 51% of households faced catastrophic costs
      compared with only 2% of the richest tertile (P < 0.01). Participants in the
      poorest tertile were more likely to be black (P < 0.01), and less likely to have
      health insurance (P < 0.01) or female full-time employment (P < 0.01). Longer
      duration of infertility was an additional risk factor for catastrophic payment (P
      < 0.05). LIMITATIONS, REASONS FOR CAUTION: No attempt was made to obtain proof of
      any payment or expenditure, and all information collected relied on participants'
      verbal account. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to
      document the frequency of catastrophic expenditure for ART using conventional
      ovarian stimulation in a low resource setting. Our results show that not all
      couples unable to afford treatment forfeit infertility care; instead poor couples
      are willing to suffer catastrophic financial hardship in order to pay. ART
      counselling therefore needs to include financial risk counselling in the short
      term. Long-term interventions comprise cost-reducing strategies as well as health
      systems strategies that reduce or eliminate the need for OPP for ART wherever
      possible. Robust evidence on mild versus conventional stimulation for ART in low
      resource settings is also required in the form of local RCTs which address the
      many clinical and health economic variables and exclude bias. Our data cannot be
      extrapolated to patients undergoing ART elsewhere or to patients undergoing ART
      with mild ovarian stimulation. STUDY FUNDING/COMPETING INTEREST(S): This study
      was funded by the Medical Research Council of South Africa and the University of
      Cape Town (University Research Committee and Faculty of Health Sciences Research
      Committee). The authors had no competing interests. TRIAL REGISTRATION NUMBER:
      not applicable.

PMID- 23878181
TI  - Patients routinely report more symptoms to experienced field enumerators than
      physicians in rural Cote d'Ivoire.
AB  - Medical history-taking is among the most powerful diagnostic tools for healthcare
      professionals. However, its accuracy and reliability are underexplored areas. The
      present post-hoc study compares medical histories from 463 people in a rural part
      of Cote d'Ivoire. The medical histories of the same individuals were taken by
      physicians and experienced field enumerators who were blinded to the results of
      the others. Kappa (kappa) statistics for 14 symptoms revealed only poor-to
      moderate agreement between physicians and field enumerators (kappa = 0.01-0.54).
      Participants reported consistently more symptoms to field enumerators than
      physicians. Only 33 (7.1%) participants gave no discordant statement at all. The
      average number of discordant statements per participant was 3.7. Poisson
      regression revealed no significant association between the number of discordant
      statements and participants' age, sex, educational attainment, occupation, or
      socioeconomic status. Operational research should further explore best practices
      to obtain reliable medical histories in resource-constrained settings.

PMID- 23878182
TI  - Zika virus infection acquired during brief travel to Indonesia.
AB  - Zika virus infection closely resembles dengue fever. It is possible that many
      cases are misdiagnosed or missed. We report a case of Zika virus infection in an
      Australian traveler who returned from Indonesia with fever and rash. Further case
      identification is required to determine the evolving epidemiology of this
      disease.

PMID- 23878183
TI  - Molecular detection of Rickettsia felis in different flea species from Caldas,
      Colombia.
AB  - Rickettsioses caused by Rickettsia felis are an emergent global threat.
      Historically, the northern region of the province of Caldas in Colombia has
      reported murine typhus cases, and recently, serological studies confirmed high
      seroprevalence for both R. felis and R. typhi. In the present study, fleas from
      seven municipalities were collected from dogs, cats, and mice. DNA was extracted
      and amplified by polymerase chain reaction (PCR) to identify gltA, ompB, and 17kD
      genes. Positive samples were sequenced to identify the species of Rickettsia. Of
      1,341 fleas, Ctenocephalides felis was the most prevalent (76.7%). Positive PCR
      results in the three genes were evidenced in C. felis (minimum infection rates;
      5.3%), C. canis (9.2%), and Pulex irritans (10.0%). Basic Local Alignment Search
      Tool (BLAST) analyses of sequences showed high identity values (> 98%) with R.
      felis, and all were highly related by phylogenetic analyses. This work shows the
      first detection of R. felis in fleas collected from animals in Colombia.

PMID- 23878184
TI  - Entomologic inoculation rates of Anopheles arabiensis in southwestern Ethiopia.
AB  - We collected anophelines every second week for one year from randomly selected
      houses in southwestern Ethiopia by using Centers for Disease Control (CDC) light
      traps, pyrethrum spray catches, and artificial pit shelter constructions to
      detect circumsporozoite proteins and estimate entomologic inoculation rates
      (EIRs). Of 3,678 Anopheles arabiensis tested for circumsporozoite proteins, 11
      were positive for Plasmodium falciparum and three for P. vivax. The estimated
      annual P. falciparum EIR of An. arabiensis was 17.1 infectious bites per person
      per year (95% confidence interval = 7.03-34.6) based on CDC light traps and 0.1
      infectious bites per person per year based on pyrethrum spray catches. The P.
      falciparum EIRs from CDC light traps varied from 0 infectious bites per person
      per year (in 60% of houses) to 73.2 infectious bites per person per year in the
      house nearest the breeding sites. Risk of exposure to infectious bites was higher
      in wet months than dry months, with a peak in April (9.6 infectious bites per
      person per month), the period of highest mosquito density.

PMID- 23878185
TI  - Changes in tuberculin skin test positivity over 20 years in periurban shantytowns
      in Lima, Peru.
AB  - A cross-sectional, community-based study was performed in 2012 with 428 residents
      of periurban shantytowns in Lima, Peru to study risk factors for and changes in
      latent tuberculosis infection in age-stratified groups compared with our data
      from the same region in 1990 (N = 219) and 2005 (N = 103). Tuberculin skin test
      positivity in these communities was highly prevalent at 52% overall, increased
      with age (P < 0.01) and was similar to 2005 (53%) and 1990 (48%). From 1990 to
      2012, the prevalence of tuberculin positivity decreased in 5-14 and 15-24 year
      old groups (to 17% and 34%, respectively, both P < 0.05). However, this may be
      explained by cessation of Bacille Calmette-Guerin revaccination during this
      period, because Bacille Calmette-Guerin revaccination doubled tuberculin
      positivity. Over the same 22-year period, tuberculin positivity in the >= 25 year
      old group remained high (71%, P = 0.3), suggesting that prevalent latent
      tuberculosis infection persists in the adult population despite improving medical
      care and socioeconomic development in this region.

PMID- 23878186
TI  - First detection of heartland virus (Bunyaviridae: Phlebovirus) from field
      collected arthropods.
AB  - Heartland virus (HRTV), the first pathogenic Phlebovirus (Family: Bunyaviridae)
      discovered in the United States, was recently described from two Missouri
      farmers. In 2012, we collected 56,428 ticks representing three species at 12
      sites including both patients' farms. Amblyomma americanum and Dermacentor
      variabilis accounted for nearly all ticks collected. Ten pools composed of
      deplete nymphs of A. americanum collected at a patient farm and a nearby
      conservation area were reverse transcription-polymerase chain reaction positive,
      and eight pools yielded viable viruses. Sequence data from the nonstructural
      protein of the Small segment indicates that tick strains and human strains are
      very similar, >= 97.6% sequence identity. This is the first study to isolate HRTV
      from field-collected arthropods and to implicate ticks as potential vectors.
      Amblyomma americanum likely becomes infected by feeding on viremic hosts during
      the larval stage, and transmission to humans occurs during the spring and early
      summer when nymphs are abundant and actively host seeking.

PMID- 23878187
TI  - Sociocultural determinants of anticipated vaccine acceptance for acute watery
      diarrhea in early childhood in Katanga Province, Democratic Republic of Congo.
AB  - Rotavirus and oral cholera vaccines have the potential to reduce diarrhea-related
      child mortality in low-income settings and are recommended by the World Health
      Organization. Uptake of vaccination depends on community support, and is based on
      local priorities. This study investigates local perceptions of acute watery
      diarrhea in childhood and anticipated vaccine acceptance in two sites in the
      Democratic Republic of Congo. In 2010, 360 randomly selected non-affected adults
      were interviewed by using a semi-structured questionnaire. Witchcraft and
      breastfeeding were perceived as potential cause of acute watery diarrhea by 51%
      and 48% of respondents. Despite misperceptions, anticipated vaccine acceptance at
      no cost was 99%. The strongest predictor of anticipated vaccine acceptance if
      costs were assumed was the educational level of the respondents. Results suggest
      that the introduction of vaccines is a local priority and local (mis)perceptions
      of illness do not compromise vaccine acceptability if the vaccine is affordable.

PMID- 23878188
TI  - Redox imbalance and biochemical changes in cancer.
AB  - For this article, we explore a hypothesis involving the possible role of
      reduction/oxidation (redox) state in cancer. We hypothesize that many
      modifications in cellular macromolecules, observed in cancer progression, may be
      caused by redox imbalance. Recent biochemical data suggest that human prostate
      cancer cell lines show a redox imbalance (oxidizing) compared with benign primary
      prostate epithelial cells; the degree of oxidation varied with aggressive
      behavior of each cell line. Our recent data suggest that human breast cancer
      tissues show a redox imbalance (reducing) compared with benign adjacent breast
      tissues. Accumulating data summarized in this article suggest that redox
      imbalance may regulate gene expression and alter protein stability by
      posttranslational modifications, in turn modulating existing cellular programs.
      Despite significant improvements in cancer therapeutics, resistance occurs, and
      redox imbalance may play a role in this process. Studies show that some cancer
      therapeutic agents increase generation of reactive oxygen/nitrogen species and
      antioxidant enzymes, which may alter total antioxidant capacity, cause cellular
      adaptation, and result in reduced effectiveness of treatment modalities.
      Approaches involving modulations of intra- and extracellular redox states, in
      combination with other therapies, may lead to new treatment options, especially
      for patients who are resistant to standard treatments.

PMID- 23878189
TI  - Interferon-alpha suppresses cAMP to disarm human regulatory T cells.
AB  - IFN-alpha is an antineoplastic agent in the treatment of several solid and
      hematologic malignancies that exerts strong immune- and autoimmune-stimulating
      activity. However, the mechanisms of immune activation by IFN-alpha remain
      incompletely understood, particularly with regard to CD4(+)CD25(high)Foxp(+)
      regulatory T cells (Treg). Here, we show that IFN-alpha deactivates the
      suppressive function of human Treg by downregulating their intracellular cAMP
      level. IFN-alpha-mediated Treg inactivation increased CD4(+) effector T-cell
      activation and natural killer cell tumor cytotoxicity. Mechanistically,
      repression of cAMP in Treg was caused by IFN-alpha-induced MAP-ERK kinase
      (MEK)/extracellular signal-regulated kinase (ERK)-mediated phosphodiesterase 4
      (PDE4) activation and accompanied by downregulation of IFN receptor (IFNAR)-2 and
      negative regulation of T-cell receptor signaling. IFN-alpha did not affect the
      anergic state, cytokine production, Foxp3 expression, or methylation state of the
      Treg-specific demethylated region (TSDR) within the FOXP3 locus associated with a
      stable imprinted phenotype of human Treg. Abrogated protection by IFN-alpha
      treated Treg in a humanized mouse model of xenogeneic graft-versus-host disease
      confirmed IFN-alpha-dependent regulation of Treg activity in vivo. Collectively,
      the present study unravels Treg inactivation as a novel IFN-alpha activity that
      provides a conceivable explanation for the immune-promoting effect and induction
      of autoimmunity by IFN-alpha treatment in patients with cancer and suggests IFN
      alpha for concomitant Treg blockade in the context of therapeutic vaccination
      against tumor antigens.

PMID- 23878190
TI  - Infiltrating macrophages promote prostate tumorigenesis via modulating androgen
      receptor-mediated CCL4-STAT3 signaling.
AB  - Infiltrating macrophages are a key component of inflammation during
      tumorigenesis, but the direct evidence of such linkage remains unclear. We report
      here that persistent coculturing of immortalized prostate epithelial cells with
      macrophages, without adding any carcinogens, induces prostate tumorigenesis and
      that induction involves the alteration of signaling of macrophage androgen
      receptor (AR)-inflammatory chemokine CCL4-STAT3 activation as well as epithelial
      to-mesenchymal transition and downregulation of p53/PTEN tumor suppressors. In
      vivo studies further showed that PTEN(+/-) mice lacking macrophage AR developed
      far fewer prostatic intraepithelial neoplasia (PIN) lesions, supporting an in
      vivo role for macrophage AR during prostate tumorigenesis. CCL4-neutralizing
      antibody effectively blocked macrophage-induced prostate tumorigenic signaling
      and targeting AR via an AR-degradation enhancer, ASC-J9, reduced CCL4 expression,
      and xenografted tumor growth in vivo. Importantly, CCL4 upregulation was
      associated with increased Snail expression and downregulation of p53/PTEN in high
      grade PIN and prostate cancer. Together, our results identify the AR-CCL4-STAT3
      axis as key regulators during prostate tumor initiation and highlight the
      important roles of infiltrating macrophages and inflammatory cytokines for the
      prostate tumorigenesis.

PMID- 23878191
TI  - Retroperitoneal epidermoid cyst in a dog.

PMID- 23878192
TI  - Comparison of the mechanical hypoalgesic effects of five alpha2-adrenoceptor
      agonists in donkeys.
AB  - Pharmacological pain management is necessary under many clinical situations, but
      in donkeys little information on analgesic drugs is available. This controlled,
      randomised, crossover, Latin-square, operator-blinded study aimed to assess and
      compare the hypoalgesic effects of intravenously administered saline and five
      alpha2-adrenoceptor agonists on mechanical nociceptive thresholds (MNT) in
      donkeys. Areas under the threshold change versus time curve values for 0-30, 30
      60, 60-90 and 90-120 minutes postdrug administration were used to compare the
      effect of treatment. As compared with saline, which did not increase MNT, the
      overall degree of mechanical hypoalgesia induced by xylazine (1.1 mg/kg),
      detomidine (20 MUg/kg), medetomidine (5 MUg/kg) and dexmedetomidine (3.5 MUg/kg)
      was limited to 0-60 minutes, and that of romifidine (100 MUg/kg) to 0-120
      minutes. Although there were no significant differences between the five alpha2
      adrenoceptor agonists during the first 30 minutes postadministration, hypoalgesia
      induced by xylazine and dexmedetomidine was significantly less intense than that
      achieved by detomidine and/or romifidine from 30 to 60 minutes. Differences in
      the overall degree of hypoalgesia induced by each of the alpha2-adrenoceptor
      agonists may influence veterinary surgeons towards choosing a particular drug
      over others for a particular donkey patient. 

PMID- 23878194
TI  - Elongator protein 3 (Elp3) lysine acetyltransferase is a tail-anchored
      mitochondrial protein in Toxoplasma gondii.
AB  - Lysine acetylation has recently emerged as an important, widespread post
      translational modification occurring on proteins that reside in multiple cellular
      compartments, including the mitochondria. However, no lysine acetyltransferase
      (KAT) has been definitively localized to this organelle to date. Here we describe
      the identification of an unusual homologue of Elp3 in early-branching protozoa in
      the phylum Apicomplexa. Elp3 is the catalytic subunit of the well-conserved
      transcription Elongator complex; however, Apicomplexa lack all other Elongator
      subunits, suggesting that the Elp3 in these organisms plays a role independent of
      transcription. Surprisingly, Elp3 in the parasites of this phylum, including
      Toxoplasma gondii (TgElp3), possesses a unique C-terminal transmembrane domain
      (TMD) that localizes the protein to the mitochondrion. As TgElp3 is devoid of
      known mitochondrial targeting signals, we used selective permeabilization studies
      to reveal that this KAT is oriented with its catalytic components facing the
      cytosol and its C-terminal TMD inserted into the outer mitochondrial membrane,
      consistent with a tail-anchored membrane protein. Elp3 trafficking to
      mitochondria is not exclusive to Toxoplasma as we also present evidence that a
      form of Elp3 localizes to these organelles in mammalian cells, supporting the
      idea that Elp3 performs novel functions across eukaryotes that are independent of
      transcriptional elongation. Importantly, we also present genetic studies that
      suggest TgElp3 is essential in Toxoplasma and must be positioned at the
      mitochondrial surface for parasite viability. 

PMID- 23878193
TI  - The concept of allosteric interaction and its consequences for the chemistry of
      the brain.
AB  - Throughout this Reflections article, I have tried to follow up on the genesis in
      the 1960s and subsequent evolution of the concept of allosteric interaction and
      to examine its consequences within the past decades, essentially in the field of
      the neuroscience. The main conclusion is that allosteric mechanisms built on
      similar structural principles operate in bacterial regulatory enzymes, gene
      repressors (and the related nuclear receptors), rhodopsin, G-protein-coupled
      receptors, neurotransmitter receptors, ion channels, and so on from prokaryotes
      up to the human brain yet with important features of their own. Thus, future
      research on these basic cybernetic sensors is expected to develop in two major
      directions: at the elementary level, toward the atomic structure and molecular
      dynamics of the conformational changes involved in signal recognition and
      transduction, but also at a higher level of organization, the contribution of
      allosteric mechanisms to the modulation of brain functions. 

PMID- 23878195
TI  - Interaction of transportin-SR2 with Ras-related nuclear protein (Ran) GTPase.
AB  - The human immunodeficiency virus type 1 (HIV-1) and other lentiviruses are
      capable of infecting non-dividing cells and, therefore, need to be imported into
      the nucleus before integration into the host cell chromatin. Transportin-SR2 (TRN
      SR2, Transportin-3, TNPO3) is a cellular karyopherin implicated in nuclear import
      of HIV-1. A model in which TRN-SR2 imports the viral preintegration complex into
      the nucleus is supported by direct interaction between TRN-SR2 and HIV-1
      integrase (IN). Residues in the C-terminal domain of HIV-1 IN that mediate
      binding to TRN-SR2 were recently delineated. As for most nuclear import cargoes,
      the driving force behind HIV-1 preintegration complex import is likely a gradient
      of the GDP- and GTP-bound forms of Ran, a small GTPase. In this study we offer
      biochemical and structural characterization of the interaction between TRN-SR2
      and Ran. By size exclusion chromatography we demonstrate stable complex formation
      of TRN-SR2 and RanGTP in solution. Consistent with the behavior of normal nuclear
      import cargoes, HIV-1 IN is released from the complex with TRN-SR2 by RanGTP.
      Although in concentrated solutions TRN-SR2 by itself was predominantly present as
      a dimer, the TRN-SR2-RanGTP complex was significantly more compact. Further
      analysis supported a model wherein one monomer of TRN-SR2 is bound to one monomer
      of RanGTP. Finally, we present a homology model of the TRN-SR2-RanGTP complex
      that is in excellent agreement with the experimental small angle x-ray scattering
      data. 

PMID- 23878196
TI  - Immobilized heavy chain-hyaluronic acid polarizes lipopolysaccharide-activated
      macrophages toward M2 phenotype.
AB  - Despite the known anti-inflammatory effect of amniotic membrane, its action
      mechanism remains largely unknown. HC-HA complex (HC-HA) purified from human
      amniotic membrane consists of high molecular weight hyaluronic acid (HA)
      covalently linked to the heavy chain (HC) 1 of inter-alpha-trypsin inhibitor. In
      this study, we show that soluble HC-HA also contained pentraxin 3 and induced the
      apoptosis of both formyl-Met-Leu-Phe or LPS-activated neutrophils and LPS
      activated macrophages while not affecting the resting cells. This enhanced
      apoptosis was caused by the inhibition of cell adhesion, spreading, and
      proliferation caused by HC-HA binding of LPS-activated macrophages and preventing
      adhesion to the plastic surface. Preferentially, soluble HC-HA promoted
      phagocytosis of apoptotic neutrophils in resting macrophages, whereas immobilized
      HC-HA promoted phagocytosis in LPS-activated macrophages. Upon concomitant LPS
      stimulation, immobilized HC-HA but not HA polarized macrophages toward the M2
      phenotype by down-regulating IRF5 protein and preventing its nuclear localization
      and by down-regulating IL-12, TNF-alpha, and NO synthase 2. Additionally, IL-10,
      TGF-beta1, peroxisome proliferator-activated receptor gamma, LIGHT (TNF
      superfamily 14), and sphingosine kinase-1 were up-regulated, and such M2
      polarization was dependent on TLR ligation. Collectively, these data suggest that
      HC-HA is a unique matrix component different from HA and uses multiple mechanisms
      to suppress M1 while promoting M2 phenotype. This anti-inflammatory action of HC
      HA is highly desirable to promote wound healing in diseases heightened by
      unsuccessful transition from M1 to M2 phenotypes. 

PMID- 23878197
TI  - The novel orally active proteasome inhibitor K-7174 exerts anti-myeloma activity
      in vitro and in vivo by down-regulating the expression of class I histone
      deacetylases.
AB  - Bortezomib therapy is now indispensable for multiple myeloma, but is associated
      with patient inconvenience due to intravenous injection and emerging drug
      resistance. The development of orally active proteasome inhibitors with distinct
      mechanisms of action is therefore eagerly awaited. Previously, we identified
      homopiperazine derivatives as a novel class of proteasome inhibitors with a
      different mode of proteasome binding from bortezomib. In this study, we show that
      K-7174, one of proteasome inhibitory homopiperazine derivatives, exhibits a
      therapeutic effect, which is stronger when administered orally than
      intravenously, without obvious side effects in a murine myeloma model. Moreover,
      K-7174 kills bortezomib-resistant myeloma cells carrying a beta5-subunit mutation
      in vivo and primary cells from a patient resistant to bortezomib. K-7174 induces
      transcriptional repression of class I histone deacetylases (HDAC1, -2, and -3)
      via caspase-8-dependent degradation of Sp1, the most potent transactivator of
      class I HDAC genes. HDAC1 overexpression ameliorates the cytotoxic effect of K
      7174 and abrogates histone hyperacetylation without affecting the accumulation of
      ubiquitinated proteins in K-7174-treated myeloma cells. Conversely, HDAC
      inhibitors enhance the activity of K-7174 with an increase in histone
      acetylation. These results suggest that class I HDACs are critical targets of K
      7174-induced cytotoxicity. It is highly anticipated that K-7174 increases the
      tolerability and convenience of patients by oral administration and has the
      clinical utility in overcoming bortezomib resistance as a single agent or in
      combination with HDAC inhibitors. 

PMID- 23878200
TI  - How can the R.E.N.A.L. nephrometry scoring system aid management of a solid renal
      mass?
AB  - OBJECTIVES. To investigate use of the R.E.N.A.L. nephrometry score in relation to
      the choice of treatment and postoperative complications for renal masses. DESIGN.
      Case series. SETTING. A tertiary referral hospital in Hong Kong. PATIENTS. Data
      of patients undergoing nephrectomy were collected retrospectively from a clinical
      database and analysed. A R.E.N.A.L. nephrometry score was allocated to each renal
      tumour by a blinded qualified radiologist, utilising computerised imaging
      systems. Patient demographics, choice of surgery (radical vs partial), and
      approaches (open vs minimally invasive) were analysed with respect to their
      R.E.N.A.L. score. RESULTS. In all, 74 patients were included during the study
      period, of which 38 underwent partial nephrectomy and 36 underwent radical
      nephrectomy. No differences between the groups were found with respect to patient
      demographics. There were significant differences between the partial and radical
      nephrectomy groups in terms of their mean nephrometry score (6.9 vs 9.3,
      P<0.001). The mean nephrometry sum was also significantly different in the open
      approach versus the minimally invasive approach in patients having partial
      nephrectomy (7.8 vs 6.0, P=0.001). There was no difference in the postoperative
      90-day morbidity and mortality in the partial nephrectomy and radical nephrectomy
      groups. CONCLUSIONS. The R.E.N.A.L. nephrometry score of a renal mass correlated
      significantly with our choice of surgery (partial vs radical) and our approach to
      surgery (open vs minimally invasive surgery), particularly in the partial
      nephrectomy group. It does not, however, correlate with postoperative
      complications. The nephrometry score provides a useful tool for objectively
      describing renal mass characteristics and enhancing better communication for the
      operative planning directed at renal masses. 

PMID- 23878198
TI  - Modulation of nitro-fatty acid signaling: prostaglandin reductase-1 is a
      nitroalkene reductase.
AB  - Inflammation, characterized by the activation of both resident and infiltrated
      immune cells, is accompanied by increased production of oxidizing and nitrating
      species. Nitrogen dioxide, the proximal nitrating species formed under these
      conditions, reacts with unsaturated fatty acids to yield nitroalkene derivatives.
      These electrophilic products modulate protein function via post-translational
      modification of susceptible nucleophilic amino acids. Nitroalkenes react with
      Keap1 to instigate Nrf2 signaling, activate heat shock response gene expression,
      and inhibit NF-kappaB-mediated signaling, inducing net anti-inflammatory and
      tissue-protective metabolic responses. We report the purification and
      characterization of a NADPH-dependent liver enzyme that reduces the nitroalkene
      moiety of nitro-oleic acid, yielding the inactive product nitro-stearic acid.
      Prostaglandin reductase-1 (PtGR-1) was identified as a nitroalkene reductase by
      protein purification and proteomic studies. Kinetic measurements, inhibition
      studies, immunological and molecular biology approaches as well as clinical
      analyses confirmed this identification. Overexpression of PtGR-1 in HEK293T cells
      promoted nitroalkene metabolism to inactive nitroalkanes, an effect that
      abrogated the Nrf2-dependent induction of heme oxygenase-1 expression by nitro
      oleic acid. These results situate PtGR-1 as a critical modulator of both the
      steady state levels and signaling activities of fatty acid nitroalkenes in vivo. 

PMID- 23878199
TI  - Identification, structure, and function of a novel type VI secretion
      peptidoglycan glycoside hydrolase effector-immunity pair.
AB  - Bacteria employ type VI secretion systems (T6SSs) to facilitate interactions with
      prokaryotic and eukaryotic cells. Despite the widespread identification of T6SSs
      among Gram-negative bacteria, the number of experimentally validated substrate
      effector proteins mediating these interactions remains small. Here, employing an
      informatics approach, we define novel families of T6S peptidoglycan glycoside
      hydrolase effectors. Consistent with the known intercellular self-intoxication
      exhibited by the T6S pathway, we observe that each effector gene is located
      adjacent to a hypothetical open reading frame encoding a putative periplasmically
      localized immunity determinant. To validate our sequence-based approach, we
      functionally investigate a representative family member from the soil-dwelling
      bacterium Pseudomonas protegens. We demonstrate that this protein is secreted in
      a T6SS-dependent manner and that it confers a fitness advantage in growth
      competition assays with Pseudomonas putida. In addition, we determined the 1.4 A
      x-ray crystal structure of this effector in complex with its cognate immunity
      protein. The structure reveals the effector shares highest overall structural
      similarity to a glycoside hydrolase family associated with peptidoglycan N
      acetylglucosaminidase activity, suggesting that T6S peptidoglycan glycoside
      hydrolase effector families may comprise significant enzymatic diversity. Our
      structural analyses also demonstrate that self-intoxication is prevented by the
      immunity protein through direct occlusion of the effector active site. This work
      significantly expands our current understanding of T6S effector diversity. 

PMID- 23878201
TI  - Efficacy of birth ball exercises on labour pain management.
AB  - OBJECTIVES: To evaluate the efficacy of a birth ball exercise programme conducted
      by physiotherapists on pain relief, psychological care, and facilitation of the
      labour process at a labour ward in a regional hospital. DESIGN: Case series with
      before-after comparisons. SETTING: Kwong Wah Hospital, Hong Kong. PARTICIPANTS:
      Chinese women admitted to the labour ward for spontaneous vaginal delivery
      between April and August 2012 were recruited. Physiotherapists taught birth ball
      exercises in groups or individually for 30 minutes. Labour pain intensity, back
      pain intensity, frequency of labour pain, stress and anxiety levels, and
      subjective pressure level over the lower abdomen were captured before and after
      birth ball exercises. Most of the parameters were measured using self-reported
      visual analogue scales. After the exercise session, physiotherapists measured the
      women's satisfaction level. Midwives recorded pethidine usage. RESULTS: A total
      of 203 pregnant women participated in this programme; 181 were in the latent
      phase group, whereas 22 were categorised into the no-labour-pain group. In both
      groups, there were statistically and clinically significant differences in back
      pain level, stress and anxiety levels, as well as pressure level over the lower
      abdomen before and after the exercise (P<0.05). In the latent phase group,
      significant decreases in labour pain and frequency of labour pain were
      demonstrated. Mean satisfaction scores were high, with visual analogue scale
      scores higher than 8.2 in both groups. Pethidine usage showed a further
      decreasing trend (6.4%) compared with the past 2 years. CONCLUSION: Birth ball
      exercise could be an alternative means of relieving back pain and labour pain in
      the labour ward, and could decrease pethidine consumption in labouring women.

PMID- 23878202
TI  - Benchtop study of leakages across the Portex, TaperGuard, and Microcuff
      endotracheal tubes under simulated clinical conditions.
AB  - OBJECTIVES. To compare three endotracheal tubes for leakage across the cuff
      (microaspiration) under a comprehensive set of simulated clinical situations.
      These were the Mallinckrodt TaperGuard (Covidien, US) with a tapered polyvinyl
      chloride cuff; the KimVent Microcuff (Kimberly-Clark Health Care, US) with a
      cylindrical polyurethane cuff; and a conventional Portex (Smiths Medical
      International Ltd, UK) with a globular polyvinyl chloride cuff. DESIGN. A
      benchtop experimental study. SETTING AND MATERIALS. A silicone cylinder serving
      as the model trachea was intubated with each of the three endotracheal tubes, one
      at a time. A total of 20 mL of water were added above the cuff and leakage
      measured every minute for 20 minutes under five simulated mechanical ventilation
      scenarios, including different positive end-expiratory pressure levels, and
      disconnection with and without spontaneous breathing efforts. Each scenario was
      studied under three cuff pressures of 10, 20 and 30 cm H2O, and then repeated
      with the application of a continuous suction force of 200 cm H2O, and leakage
      measured every minute for 3 minutes. RESULTS. The outcome of interest was the
      cumulative amount of leakage. The Microcuff endotracheal tubes with an ultrathin
      polyurethane cuff consistently provided the best protection against
      microaspiration under all simulated clinical situations, followed by TaperGuard
      with a tapered cuff, and lastly Portex with a globular polyvinyl chloride cuff.
      Clinical scenarios associated with the greatest leakage were mechanical
      ventilation with zero positive end-expiratory pressure, circuit disconnection
      with spontaneous breathing efforts, application of suction, and a low cuff
      pressure. CONCLUSIONS. Microcuff endotracheal tubes outperformed TaperGuard and
      Portex endotracheal tubes in preventing microaspiration, which is one of the
      major mechanisms for ventilator-associated pneumonia. 

PMID- 23878203
TI  - Ultrasound-guided plugged percutaneous biopsy of solid organs in patients with
      bleeding tendencies.
AB  - OBJECTIVE: To establish and verify the utility of plugging biopsy tracts, using a
      combination of Gelfoam slurry and torpedo in the prevention of post-biopsy
      bleeding in patients at high risk of post-procedure haemorrhage following
      ultrasound-guided percutaneous biopsy of solid organs. DESIGN: Case series.
      SETTING: Radiology Department of a regional hospital in Hong Kong. PATIENTS: In
      our unit, all patients considered to be at high risk of post-biopsy haemorrhage
      of a solid organ underwent ultrasound-guided plugged percutaneous biopsy from
      year 2005 to 2012. INTERVENTIONS: All the included patients had undergone real
      time ultrasound-guided biopsy of solid organs (liver in 10 and spleen in one
      patient). In all cases, a combination of a coaxial introducer needle and Temno
      needle were used. After adequate specimens were obtained, Gelfoam slurry (for
      distal embolisation) followed by Gelfoam torpedo (for proximal embolisation) were
      used to plug the biopsy tract. MAIN OUTCOME MEASURES: Technical success, any post
      biopsy haemorrhage treated by transfusion or other intervention, and plugging
      related complications were reviewed for each patient. RESULTS: Technical success
      was achieved in all patients and none experienced post-biopsy haemorrhage treated
      by blood transfusion or any other intervention. CONCLUSION: Plugging of the
      biopsy tract with Gelfoam slurry followed by Gelfoam torpedo is a direct and
      simple procedure that can safely and effectively prevent haemorrhage in patients
      at high risk of post-biopsy haemorrhage.

PMID- 23878204
TI  - Intrarater test-retest reliability of static and dynamic stability indexes
      measurement using the Biodex Stability System during unilateral stance.
AB  - The measurements of postural balance often involve measurement error, which
      affects the analysis and interpretation of the outcomes. In most of the existing
      clinical rehabilitation research, the ability to produce reliable measures is a
      prerequisite for an accurate assessment of an intervention after a period of
      time. Although clinical balance assessment has been performed in previous study,
      none has determined the intrarater test-retest reliability of static and dynamic
      stability indexes during dominant single stance. In this study, one rater
      examined 20 healthy university students (female=12, male=8) in two sessions
      separated by 7 day intervals. Three stability indexes--the overall stability
      index (OSI), anterior/posterior stability index (APSI), and medial/ lateral
      stability index (MLSI) in static and dynamic conditions--were measured during
      single dominant stance. Intraclass correlation coefficient (ICC), standard error
      measurement (SEM) and 95% confidence interval (95% CI) were calculated. Test
      retest ICCs for OSI, APSI, and MLSI were 0.85, 0.78, and 0.84 during static
      condition and were 0.77, 0.77, and 0.65 during dynamic condition, respectively.
      We concluded that the postural stability assessment using Biodex stability system
      demonstrates good-to-excellent test-retest reliability over a 1 week time
      interval.

PMID- 23878205
TI  - A kinetic and kinematic analysis of the effect of stochastic resonance electrical
      stimulation and knee sleeve during gait in osteoarthritis of the knee.
AB  - Extended use of knee sleeves in populations at risk for knee osteoarthritis
      progression has shown functional and quality of life benefits; however,
      additional comprehensive kinematic and kinetic analyses are needed to determine
      possible physical mechanisms of these benefits which may be due to the sleeve's
      ability to enhance knee proprioception. A novel means of extending these
      enhancements may be through stochastic resonance stimulation. Our goal was to
      determine whether the use of a knee sleeve alone or combined with stochastic
      resonance electrical stimulation improves knee mechanics in knee osteoarthritis.
      Gait kinetics and kinematics were assessed in subjects with medial knee
      osteoarthritis when presented with four conditions: control1, no electrical
      stimulation/sleeve, 75% threshold stimulation/sleeve, and control2. An increase
      in knee flexion angle throughout stance and a decrease in flexion moment
      occurring immediately after initial contact were seen in the stimulation/sleeve
      and sleeve alone conditions; however, these treatment conditions did not affect
      the knee adduction angle and internal knee abduction moment during weight
      acceptance. No differences were found between the sleeve alone and the stochastic
      resonance with sleeve conditions. A knee sleeve can improve sagittal-plane knee
      kinematics and kinetics, although adding the current configuration of stochastic
      resonance did not enhance these effects. 

PMID- 23878206
TI  - Frontal plane knee and hip kinematics during sit-to-stand and proximal lower
      extremity strength in persons with patellofemoral osteoarthritis: a pilot study.
AB  - Increased joint stress and malalignment are etiologic factors in osteoarthritis.
      Static tibiofemoral frontal plane malalignment is associated with patellofemoral
      osteoarthritis (PFOA). Patellofemoral joint stress is increased by activities
      such as sit-to-stand (STS); this stress may be even greater if dynamic frontal
      plane tibiofemoral malalignment occurs. If hip muscle or quadriceps weakness is
      present in persons with PFOA, aberrant tibiofemoral frontal plane movement may
      occur, with increased patellofemoral stress. No studies have investigated frontal
      plane tibiofemoral and hip kinematics during STS in persons with PFOA or the
      relationship of hip muscle and quadriceps strength to these motions. Eight PFOA
      and seven control subjects performed STS from a stool during three-dimensional
      motion capture. Hip muscle and quadriceps strength were measured as peak
      isometric force. The PFOA group demonstrated increased peak tibial abduction
      angles during STS, and decreased hip abductor, hip extensor, and quadriceps peak
      force versus controls. A moderate inverse relationship between peak tibial
      abduction angle and peak hip abductor force was present. No difference between
      groups was found for peak hip adduction angle or peak hip external rotator force.
      Dynamic tibiofemoral malalignment and proximal lower extremity weakness may cause
      increased patellofemoral stress and may contribute to PFOA incidence or
      progression. 

PMID- 23878207
TI  - Kinetics of badminton lunges in four directions.
AB  - The lunge is the most fundamental skill in badminton competitions. Fifteen
      university-level male badminton players performed lunge maneuvers in four
      directions, namely, right-forward, left-forward, right-backward, and left
      backward, while wearing two different brands of badminton shoes. The test
      compared the kinetics of badminton shoes in performing typical lunge maneuvers. A
      force plate and an insole measurement system measured the ground reaction forces
      and plantar pressures. These measurements were compared across all lunge
      maneuvers. The left-forward lunge generated significantly higher first vertical
      impact force (2.34 +/- 0.52 BW) than that of the right-backward (2.06 +/- 0.60
      BW) and left-backward lunges (1.78 +/- 0.44 BW); higher second vertical impact
      force (2.44 +/- 0.51 BW) than that of the left-backward lunge (2.07 +/- 0.38 BW);
      and higher maximum anterior-posterior shear force (1.48 +/- 0.36 BW) than that of
      the left-backward lunge (1.18 +/- 0.38 BW). Compared with other lunge directions,
      the left-forward lunge showed higher mean maximum vertical impact anterior
      posterior shear forces and their respective maximum loading rates, and the
      plantar pressure at the total foot and heel regions. Therefore, the left-forward
      lunge is a critical maneuver for badminton biomechanics and related footwear
      research because of the high loading magnitude generated during heel impact. 

PMID- 23878208
TI  - Do qualitative changes in interlimb coordination lead to effectiveness of aquatic
      locomotion rather than efficiency?
AB  - This study compared interlimb coordination and indicators of swim efficiency and
      effectiveness between expert and recreational breaststroke swimmers. Arm-leg
      coordination of 8 expert and 10 recreational swimmers at two different paces,
      slow and sprint, were compared using relative phase between elbow and knee. For
      each participant, knee and elbow angles were assessed using a 3-dimensional video
      analysis system with four below and two above cameras. During each phase of the
      cycle, indicators of swim efficiency (intracyclic velocity variations) and
      effectiveness (horizontal distance, velocity peaks, acceleration peaks) were
      calculated. Two coordination patterns emerged between expert and recreational
      swimmers, with significant differences in the relative phase at the beginning of
      a cycle (-172.4 degrees  for experts and -106.6 degrees  for recreational
      swimmers) and the maximum value of relative phase (9.1 degrees  for experts and
      45.9 degrees  for recreational swimmers; all P<.05). Experts' coordination was
      associated with higher swim effectiveness (higher acceleration peak: 2.4 m/s2 for
      experts and 1.6 m/s2 for recreational swimmers) and higher distance covered by
      the center of mass during each phase of the cycle (all P<.05). This study
      emphasized how experts coordinate arms and legs to achieve effective behavior,
      therefore exhibiting flexibility, mainly in the timing of the glide phase, to
      adapt to different speed.

PMID- 23878210
TI  - Agent-based Bayesian approach to monitoring the progress of invasive species
      eradication programs.
AB  - Eradication of an invasive species can provide significant environmental,
      economic, and social benefits, but eradication programs often fail. Constant and
      careful monitoring improves the chance of success, but an invasion may seem to be
      in decline even when it is expanding in abundance or spatial extent. Determining
      whether an invasion is in decline is a challenging inference problem for two
      reasons. First, it is typically infeasible to regularly survey the entire
      infested region owing to high cost. Second, surveillance methods are imperfect
      and fail to detect some individuals. These two factors also make it difficult to
      determine why an eradication program is failing. Agent-based methods enable
      inferences to be made about the locations of undiscovered individuals over time
      to identify trends in invader abundance and spatial extent. We develop an agent
      based Bayesian method and apply it to Australia's largest eradication program:
      the campaign to eradicate the red imported fire ant (Solenopsis invicta) from
      Brisbane. The invasion was deemed to be almost eradicated in 2004 but our
      analyses indicate that its geographic range continued to expand despite a sharp
      decline in number of nests. We also show that eradication would probably have
      been achieved with a relatively small increase in the area searched and treated.
      Our results demonstrate the importance of inferring temporal and spatial trends
      in ongoing invasions. The method can handle incomplete observations and takes
      into account the effects of human intervention. It has the potential to transform
      eradication practices. 

PMID- 23878209
TI  - Stimulus-dependent variability and noise correlations in cortical MT neurons.
AB  - Population codes assume that neural systems represent sensory inputs through the
      firing rates of populations of differently tuned neurons. However, trial-by-trial
      variability and noise correlations are known to affect the information capacity
      of neural codes. Although recent studies have shown that stimulus presentation
      reduces both variability and rate correlations with respect to their spontaneous
      level, possibly improving the encoding accuracy, whether these second order
      statistics are tuned is unknown. If so, second-order statistics could themselves
      carry information, rather than being invariably detrimental. Here we show that
      rate variability and noise correlation vary systematically with stimulus
      direction in directionally selective middle temporal (MT) neurons, leading to
      characteristic tuning curves. We show that such tuning emerges in a stochastic
      recurrent network, for a set of connectivity parameters that overlaps with a
      single-state scenario and multistability. Information theoretic analysis shows
      that second-order statistics carry information that can improve the accuracy of
      the population code. 

PMID- 23878211
TI  - HLA targeting efficiency correlates with human T-cell response magnitude and with
      mortality from influenza A infection.
AB  - Experimental and computational evidence suggests that HLAs preferentially bind
      conserved regions of viral proteins, a concept we term "targeting efficiency,"
      and that this preference may provide improved clearance of infection in several
      viral systems. To test this hypothesis, T-cell responses to A/H1N1 (2009) were
      measured from peripheral blood mononuclear cells obtained from a household cohort
      study performed during the 2009-2010 influenza season. We found that HLA
      targeting efficiency scores significantly correlated with IFN-gamma enzyme-linked
      immunosorbent spot responses (P = 0.042, multiple regression). A further
      population-based analysis found that the carriage frequencies of the alleles with
      the lowest targeting efficiencies, A*24, were associated with pH1N1 mortality (r
      = 0.37, P = 0.031) and are common in certain indigenous populations in which
      increased pH1N1 morbidity has been reported. HLA efficiency scores and HLA use
      are associated with CD8 T-cell magnitude in humans after influenza infection. The
      computational tools used in this study may be useful predictors of potential
      morbidity and identify immunologic differences of new variant influenza strains
      more accurately than evolutionary sequence comparisons. Population-based studies
      of the relative frequency of these alleles in severe vs. mild influenza cases
      might advance clinical practices for severe H1N1 infections among genetically
      susceptible populations. 

PMID- 23878212
TI  - Advertisements impact the physiological efficacy of a branded drug.
AB  - We conducted randomized clinical trials to examine the impact of direct-to
      consumer advertisements on the efficacy of a branded drug. We compared the
      objectively measured, physiological effect of Claritin (Merck & Co.), a leading
      antihistamine medication, across subjects randomized to watch a movie spliced
      with advertisements for Claritin or advertisements for Zyrtec (McNeil), a
      competitor antihistamine. Among subjects who test negative for common allergies,
      exposure to Claritin advertisements rather than Zyrtec advertisements increases
      the efficacy of Claritin. We conclude that branded drugs can interact with
      exposure to television advertisements. 

PMID- 23878214
TI  - Universal collapse of stress and wrinkle-to-scar transition in spherically
      confined crystalline sheets.
AB  - Imposing curvature on crystalline sheets, such as 2D packings of colloids or
      proteins, or covalently bonded graphene leads to distinct types of structural
      instabilities. The first type involves the proliferation of localized defects
      that disrupt the crystalline order without affecting the imposed shape, whereas
      the second type consists of elastic modes, such as wrinkles and crumples, which
      deform the shape and also are common in amorphous polymer sheets. Here, we
      propose a profound link between these types of patterns, encapsulated in a
      universal, compression-free stress field, which is determined solely by the
      macroscale confining conditions. This "stress universality" principle and a few
      of its immediate consequences are borne out by studying a circular crystalline
      patch bound to a deformable spherical substrate, in which the two distinct
      patterns become, respectively, radial chains of dislocations (called "scars") and
      radial wrinkles. The simplicity of this set-up allows us to characterize the
      morphologies and evaluate the energies of both patterns, from which we construct
      a phase diagram that predicts a wrinkle-scar transition in confined crystalline
      sheets at a critical value of the substrate stiffness. The construction of a
      unified theoretical framework that bridges inelastic crystalline defects and
      elastic deformations opens unique research directions. Beyond the potential use
      of this concept for finding energy-optimizing packings in curved topographies,
      the possibility of transforming defects into shape deformations that retain the
      crystalline structure may be valuable for a broad range of material applications,
      such as manipulations of graphene's electronic structure. 

PMID- 23878213
TI  - Intrinsic gray-matter connectivity of the brain in adults with autism spectrum
      disorder.
AB  - Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that
      are accompanied by atypical brain connectivity. So far, in vivo evidence for
      atypical structural brain connectivity in ASD has mainly been based on
      neuroimaging studies of cortical white matter. However, genetic studies suggest
      that abnormal connectivity in ASD may also affect neural connections within the
      cortical gray matter. Such intrinsic gray-matter connections are inherently more
      difficult to describe in vivo but may be inferred from a variety of surface-based
      geometric features that can be measured using magnetic resonance imaging. Here,
      we present a neuroimaging study that examines the intrinsic cortico-cortical
      connectivity of the brain in ASD using measures of "cortical separation
      distances" to assess the global and local intrinsic "wiring costs" of the cortex
      (i.e., estimated length of horizontal connections required to wire the cortex
      within the cortical sheet). In a sample of 68 adults with ASD and matched
      controls, we observed significantly reduced intrinsic wiring costs of cortex in
      ASD, both globally and locally. Differences in global and local wiring cost were
      predominantly observed in fronto-temporal regions and also significantly
      predicted the severity of social and repetitive symptoms (respectively). Our
      study confirms that atypical cortico-cortical "connectivity" in ASD is not
      restricted to the development of white-matter connections but may also affect the
      intrinsic gray-matter architecture (and connectivity) within the cortical sheet.
      Thus, the atypical connectivity of the brain in ASD is complex, affecting both
      gray and white matter, and forms part of the core neural substrates underlying
      autistic symptoms. 

PMID- 23878216
TI  - Single pollinator species losses reduce floral fidelity and plant reproductive
      function.
AB  - Understanding the functional impacts of pollinator species losses on plant
      populations is critical given ongoing pollinator declines. Simulation models of
      pollination networks suggest that plant communities will be resilient to losing
      many or even most of the pollinator species in an ecosystem. These predictions,
      however, have not been tested empirically and implicitly assume that pollination
      efficacy is unaffected by interactions with interspecific competitors. By
      contrast, ecological theory and data from a wide range of ecosystems show that
      interspecific competition can drive variation in ecological specialization over
      short timescales via behavioral or morphological plasticity, although the
      potential implications of such changes in specialization for ecosystem
      functioning remain unexplored. We conducted manipulative field experiments in
      which we temporarily removed single pollinator species from study plots in
      subalpine meadows, to test the hypothesis that interactions between pollinator
      species can shape individual species' functional roles via changes in foraging
      specialization. We show that loss of a single pollinator species reduces floral
      fidelity (short-term specialization) in the remaining pollinators, with
      significant implications for ecosystem functioning in terms of reduced plant
      reproduction, even when potentially effective pollinators remained in the system.
      Our results suggest that ongoing pollinator declines may have more serious
      negative implications for plant communities than is currently assumed. More
      broadly, we show that the individual functional contributions of species can be
      dynamic and shaped by the community of interspecific competitors, thereby
      documenting a distinct mechanism for how biodiversity can drive ecosystem
      functioning, with potential relevance to a wide range of taxa and systems. 

PMID- 23878215
TI  - Synthesizing cognition in neuromorphic electronic systems.
AB  - The quest to implement intelligent processing in electronic neuromorphic systems
      lacks methods for achieving reliable behavioral dynamics on substrates of
      inherently imprecise and noisy neurons. Here we report a solution to this problem
      that involves first mapping an unreliable hardware layer of spiking silicon
      neurons into an abstract computational layer composed of generic reliable
      subnetworks of model neurons and then composing the target behavioral dynamics as
      a "soft state machine" running on these reliable subnets. In the first step, the
      neural networks of the abstract layer are realized on the hardware substrate by
      mapping the neuron circuit bias voltages to the model parameters. This mapping is
      obtained by an automatic method in which the electronic circuit biases are
      calibrated against the model parameters by a series of population activity
      measurements. The abstract computational layer is formed by configuring neural
      networks as generic soft winner-take-all subnetworks that provide reliable
      processing by virtue of their active gain, signal restoration, and
      multistability. The necessary states and transitions of the desired high-level
      behavior are then easily embedded in the computational layer by introducing only
      sparse connections between some neurons of the various subnets. We demonstrate
      this synthesis method for a neuromorphic sensory agent that performs real-time
      context-dependent classification of motion patterns observed by a silicon retina.

PMID- 23878217
TI  - Bottlenose dolphins can use learned vocal labels to address each other.
AB  - In animal communication research, vocal labeling refers to incidents in which an
      animal consistently uses a specific acoustic signal when presented with a
      specific object or class of objects. Labeling with learned signals is a
      foundation of human language but is notably rare in nonhuman communication
      systems. In natural animal systems, labeling often occurs with signals that are
      not influenced by learning, such as in alarm and food calling. There is a
      suggestion, however, that some species use learned signals to label conspecific
      individuals in their own communication system when mimicking individually
      distinctive calls. Bottlenose dolphins (Tursiops truncatus) are a promising
      animal for exploration in this area because they are capable of vocal production
      learning and can learn to use arbitrary signals to report the presence or absence
      of objects. Bottlenose dolphins develop their own unique identity signal, the
      signature whistle. This whistle encodes individual identity independently of
      voice features. The copying of signature whistles may therefore allow animals to
      label or address one another. Here, we show that wild bottlenose dolphins respond
      to hearing a copy of their own signature whistle by calling back. Animals did not
      respond to whistles that were not their own signature. This study provides
      compelling evidence that a dolphin's learned identity signal is used as a label
      when addressing conspecifics. Bottlenose dolphins therefore appear to be unique
      as nonhuman mammals to use learned signals as individually specific labels for
      different social companions in their own natural communication system. 

PMID- 23878218
TI  - Dietary gluten triggers concomitant activation of CD4+ and CD8+ alphabeta T cells
      and gammadelta T cells in celiac disease.
AB  - Celiac disease is an intestinal autoimmune disease driven by dietary gluten and
      gluten-specific CD4(+) T-cell responses. In celiac patients on a gluten-free
      diet, exposure to gluten induces the appearance of gluten-specific CD4(+) T cells
      with gut-homing potential in the peripheral blood. Here we show that gluten
      exposure also induces the appearance of activated, gut-homing CD8(+) alphabeta
      and gammadelta T cells in the peripheral blood. Single-cell T-cell receptor
      sequence analysis indicates that both of these cell populations have highly
      focused T-cell receptor repertoires, indicating that their induction is antigen
      driven. These results reveal a previously unappreciated role of antigen in the
      induction of CD8(+) alphabeta and gammadelta T cells in celiac disease and
      demonstrate a coordinated response by all three of the major types of T cells.
      More broadly, these responses may parallel adaptive immune responses to viral
      pathogens and other systemic autoimmune diseases. 

PMID- 23878219
TI  - Six-rowed spike4 (Vrs4) controls spikelet determinacy and row-type in barley.
AB  - Inflorescence architecture of barley (Hordeum vulgare L.) is common among the
      Triticeae species, which bear one to three single-flowered spikelets at each
      rachis internode. Triple spikelet meristem is one of the unique features of
      barley spikes, in which three spikelets (one central and two lateral spikelets)
      are produced at each rachis internode. Fertility of the lateral spikelets at
      triple spikelet meristem gives row-type identity to barley spikes. Six-rowed
      spikes show fertile lateral spikelets and produce increased grain yield per
      spike, compared with two-rowed spikes with sterile lateral spikelets. Thus, far,
      two loci governing the row-type phenotype were isolated in barley that include
      Six-rowed spike1 (Vrs1) and Intermedium-C. In the present study, we isolated Six
      rowed spike4 (Vrs4), a barley ortholog of the maize (Zea mays L.) inflorescence
      architecture gene RAMOSA2 (RA2). Eighteen coding mutations in barley RA2 (HvRA2)
      were specifically associated with lateral spikelet fertility and loss of spikelet
      determinacy. Expression analyses through mRNA in situ hybridization and
      microarray showed that Vrs4 (HvRA2) controls the row-type pathway through Vrs1
      (HvHox1), a negative regulator of lateral spikelet fertility in barley. Moreover,
      Vrs4 may also regulate transcripts of barley SISTER OF RAMOSA3 (HvSRA), a
      putative trehalose-6-phosphate phosphatase involved in trehalose-6-phosphate
      homeostasis implicated to control spikelet determinacy. Our expression data
      illustrated that, although RA2 is conserved among different grass species, its
      down-stream target genes appear to be modified in barley and possibly other
      species of tribe Triticeae. 

PMID- 23878220
TI  - Homologous 2',5'-phosphodiesterases from disparate RNA viruses antagonize
      antiviral innate immunity.
AB  - Efficient and productive virus infection often requires viral countermeasures
      that block innate immunity. The IFN-inducible 2',5'-oligoadenylate (2-5A)
      synthetases (OASs) and ribonuclease (RNase) L are components of a potent host
      antiviral pathway. We previously showed that murine coronavirus (MHV) accessory
      protein ns2, a 2H phosphoesterase superfamily member, is a phosphodiesterase
      (PDE) that cleaves 2-5A, thereby preventing activation of RNase L. The PDE
      activity of ns2 is required for MHV replication in macrophages and for hepatitis.
      Here, we show that group A rotavirus (RVA), an important cause of acute
      gastroenteritis in children worldwide, encodes a similar PDE. The RVA PDE forms
      the carboxy-terminal domain of the minor core protein VP3 (VP3-CTD) and shares
      sequence and predicted structural homology with ns2, including two catalytic
      HxT/S motifs. Bacterially expressed VP3-CTD exhibited 2',5'-PDE activity, which
      cleaved 2-5A in vitro. In addition, VP3-CTD expressed transiently in mammalian
      cells depleted 2-5A levels induced by OAS activation with poly(rI):poly(rC),
      preventing RNase L activation. In the context of recombinant chimeric MHV
      expressing inactive ns2, VP3-CTD restored the ability of the virus to replicate
      efficiently in macrophages or in the livers of infected mice, whereas mutant
      viruses expressing inactive VP3-CTD (H718A or H798R) were attenuated. In
      addition, chimeric viruses expressing either active ns2 or VP3-CTD, but not
      nonfunctional equivalents, were able to protect ribosomal RNA from RNase L
      mediated degradation. Thus, VP3-CTD is a 2',5'-PDE able to functionally
      substitute for ns2 in MHV infection. Remarkably, therefore, two disparate RNA
      viruses encode proteins with homologous 2',5'-PDEs that antagonize activation of
      innate immunity. 

PMID- 23878221
TI  - Inflammatory monocytes are potent antitumor effectors controlled by regulatory
      CD4+ T cells.
AB  - The present study evaluates the impact of immune cell populations on metastatic
      development in a model of spontaneous melanoma [mice expressing the human RET
      oncogene under the control of the metallothionein promoter (MT/ret mice)]. In
      this model, cancer cells disseminate early but remain dormant for several weeks.
      Then, MT/ret mice develop cutaneous metastases and, finally, distant metastases.
      A total of 35% of MT/ret mice develop a vitiligo, a skin depigmentation
      attributable to the lysis of normal melanocytes, associated with a delay in tumor
      progression. Here, we find that regulatory CD4(+) T cells accumulate in the skin,
      the spleen, and tumor-draining lymph nodes of MT/ret mice not developing
      vitiligo. Regulatory T-cell depletion and IL-10 neutralization led to increased
      occurrence of vitiligo that correlated with a decreased incidence of melanoma
      metastases. In contrast, inflammatory monocytes/dendritic cells accumulate in the
      skin of MT/ret mice with active vitiligo. Moreover, they inhibit tumor cell
      proliferation in vitro through a reactive oxygen species-dependent mechanism, and
      both their depletion and reactive oxygen species neutralization in vivo increased
      tumor cell dissemination. Altogether, our data suggest that regulatory CD4(+) T
      cells favor tumor progression, in part, by inhibiting recruitment and/or
      differentiation of inflammatory monocytes in the skin. 

PMID- 23878222
TI  - Nucleosome maps of the human cytomegalovirus genome reveal a temporal switch in
      chromatin organization linked to a major IE protein.
AB  - Human CMV (hCMV) establishes lifelong infections in most of us, causing
      developmental defects in human embryos and life-threatening disease in
      immunocompromised individuals. During productive infection, the viral >230,000-bp
      dsDNA genome is expressed widely and in a temporal cascade. The hCMV genome does
      not carry histones when encapsidated but has been proposed to form nucleosomes
      after release into the host cell nucleus. Here, we present hCMV genome-wide
      nucleosome occupancy and nascent transcript maps during infection of permissive
      human primary cells. We show that nucleosomes occupy nuclear viral DNA in a
      nonrandom and highly predictable fashion. At early times of infection,
      nucleosomes associate with the hCMV genome largely according to their intrinsic
      DNA sequence preferences, indicating that initial nucleosome formation is
      genetically encoded in the virus. However, as infection proceeds to the late
      phase, nucleosomes redistribute extensively to establish patterns mostly
      determined by nongenetic factors. We propose that these factors include key
      regulators of viral gene expression encoded at the hCMV major immediate-early
      (IE) locus. Indeed, mutant virus genomes deficient for IE1 expression exhibit
      globally increased nucleosome loads and reduced nucleosome dynamics compared with
      WT genomes. The temporal nucleosome occupancy differences between IE1-deficient
      and WT viruses correlate inversely with changes in the pattern of viral nascent
      and total transcript accumulation. These results provide a framework of spatial
      and temporal nucleosome organization across the genome of a major human pathogen
      and suggest that an hCMV major IE protein governs overall viral chromatin
      structure and function. 

PMID- 23878223
TI  - Experimental and computational analysis of the transition state for ribonuclease
      A-catalyzed RNA 2'-O-transphosphorylation.
AB  - Enzymes function by stabilizing reaction transition states; therefore, comparison
      of the transition states of enzymatic and nonenzymatic model reactions can
      provide insight into biological catalysis. Catalysis of RNA 2'-O
      transphosphorylation by ribonuclease A is proposed to involve electrostatic
      stabilization and acid/base catalysis, although the structure of the rate
      limiting transition state is uncertain. Here, we describe coordinated kinetic
      isotope effect (KIE) analyses, molecular dynamics simulations, and quantum
      mechanical calculations to model the transition state and mechanism of RNase A.
      Comparison of the (18)O KIEs on the 2'O nucleophile, 5'O leaving group, and
      nonbridging phosphoryl oxygens for RNase A to values observed for hydronium- or
      hydroxide-catalyzed reactions indicate a late anionic transition state. Molecular
      dynamics simulations using an anionic phosphorane transition state mimic suggest
      that H-bonding by protonated His12 and Lys41 stabilizes the transition state by
      neutralizing the negative charge on the nonbridging phosphoryl oxygens. Quantum
      mechanical calculations consistent with the experimental KIEs indicate that
      expulsion of the 5'O remains an integral feature of the rate-limiting step both
      on and off the enzyme. Electrostatic interactions with positively charged amino
      acid site chains (His12/Lys41), together with proton transfer from His119, render
      departure of the 5'O less advanced compared with the solution reaction and
      stabilize charge buildup in the transition state. The ability to obtain a
      chemically detailed description of 2'-O-transphosphorylation transition states
      provides an opportunity to advance our understanding of biological catalysis
      significantly by determining how the catalytic modes and active site environments
      of phosphoryl transferases influence transition state structure. 

PMID- 23878224
TI  - Paradoxical role of the proto-oncogene Axl and Mer receptor tyrosine kinases in
      colon cancer.
AB  - The receptor tyrosine kinases Axl and Mer, belonging to the Tyro3, Axl and Mer
      (TAM) receptor family, are expressed in a number of tumor cells and have well
      characterized oncogenic roles. The therapeutic targeting of these kinases is
      considered an anticancer strategy, and various inhibitors are currently under
      development. At the same time, Axl and Mer are expressed in dendritic cells and
      macrophages and have an essential function in limiting inflammation. Inflammation
      is an enabling characteristic of multiple cancer hallmarks. These contrasting
      oncogenic and anti-inflammatory functions of Axl and Mer posit a potential
      paradox in terms of anticancer therapy. Here we demonstrate that azoxymethane
      (AOM) and dextran sulfate sodium (DSS)-induced inflammation-associated cancer is
      exacerbated in mice lacking Axl and Mer. Ablation of Axl and Mer signaling is
      associated with increased production of proinflammatory cytokines and failure to
      clear apoptotic neutrophils in the intestinal lamina propria, thereby favoring a
      tumor-promoting environment. Interestingly, loss of these genes in the
      hematopoietic compartment is not associated with increased colitis. Axl and Mer
      are expressed in radioresistant intestinal macrophages, and the loss of these
      genes is associated with an increased inflammatory signature in this compartment.
      Our results raise the possibility of potential adverse effects of systemic
      anticancer therapies with Axl and Mer inhibitors, and underscore the importance
      of understanding their tissue and cell type-specific functions in cancer. 

PMID- 23878225
TI  - Interphase cytofission maintains genomic integrity of human cells after failed
      cytokinesis.
AB  - In cell division, cytokinesis is tightly coupled with mitosis to maintain genomic
      integrity. Failed cytokinesis in humans can result in tetraploid cells that can
      become aneuploid and promote cancer. However, the likelihood of aneuploidy and
      cancer after a failed cytokinesis event is unknown. Here we evaluated cell fate
      after failed cytokinesis. We interrupted cytokinesis by brief chemical treatments
      in cell populations of human epithelial lines. Surprisingly, up to 50% of the
      resulting binucleate cells generated colonies. In RPE1 cells, 90% of colonies
      obtained from binucleate founders had a karyotype that matched the parental cell
      type. Time-lapse videomicroscopy demonstrated that binucleate cells are delayed
      in the first growth phase of the cell cycle (G1) and undergo interphase cellular
      fission (cytofission) that distributes nuclei into separate daughters. The
      fission is not compatible with delayed cytokinesis because events occur in the
      absence of polymerized microtubules and without canonical components of the
      cytokinetic machinery. However, the cytofission can be interrupted by inhibiting
      function of actin or myosin II. Fission events occur in both two- and three
      dimensional culture. Our data demonstrate that cytofission can preserve genomic
      integrity after failed cytokinesis. Thus, traction-mediated cytofission,
      originally observed in Dictyostelium, is relevant to human biology--where it
      seems to be an evolutionarily conserved mechanism that can preserve genomic
      integrity.

PMID- 23878226
TI  - Structural and functional insight into an unexpectedly selective N
      methyltransferase involved in plantazolicin biosynthesis.
AB  - Plantazolicin (PZN), a polyheterocyclic, N(alpha),N(alpha)-dimethylarginine
      containing antibiotic, harbors remarkably specific bactericidal activity toward
      strains of Bacillus anthracis, the causative agent of anthrax. Previous studies
      demonstrated that genetic deletion of the S-adenosyl-L-methionine-dependent
      methyltransferase from the PZN biosynthetic gene cluster results in the formation
      of desmethylPZN, which is devoid of antibiotic activity. Here we describe the in
      vitro reconstitution, mutational analysis, and X-ray crystallographic structure
      of the PZN methyltransferase. Unlike all other known small molecule
      methyltransferases, which act upon diverse substrates in vitro, the PZN
      methyltransferase is uncharacteristically limited in substrate scope and
      functions only on desmethylPZN and close derivatives. The crystal structures of
      two related PZN methyltransferases, solved to 1.75 A (Bacillus amyloliquefaciens)
      and 2.0 A (Bacillus pumilus), reveal a deep, narrow cavity, putatively
      functioning as the binding site for desmethylPZN. The narrowness of this cavity
      provides a framework for understanding the molecular basis of the extreme
      substrate selectivity. Analysis of a panel of point mutations to the
      methyltransferase from B. amyloliquefaciens allowed the identification of
      residues of structural and catalytic importance. These findings further our
      understanding of one set of orthologous enzymes involved in thiazole/oxazole
      modified microcin biosynthesis, a rapidly growing sector of natural products
      research.

PMID- 23878227
TI  - Regulation of adipose tissue T cell subsets by Stat3 is crucial for diet-induced
      obesity and insulin resistance.
AB  - Dysregulated inflammation in adipose tissue, marked by increased proinflammatory
      T-cell accumulation and reduced regulatory T cells (Tregs), contributes to
      obesity-associated insulin resistance. The molecular mechanisms underlying T-cell
      mediated inflammation in adipose tissue remain largely unknown, however. Here we
      show a crucial role for signal transducer and activator of transcription 3
      (Stat3) in T cells in skewing adaptive immunity in visceral adipose tissue (VAT),
      thereby contributing to diet-induced obesity (DIO) and insulin resistance. Stat3
      activity is elevated in obese VAT and in VAT-resident T cells. Functional
      ablation of Stat3 in T cells reduces DIO, improves insulin sensitivity and
      glucose tolerance, and suppresses VAT inflammation. Importantly, Stat3 ablation
      reverses the high Th1/Treg ratio in VAT of DIO mice that is likely secondary to
      elevated IL-6 production, leading in turn to suppression of Tregs. In addition,
      Stat3 in T cells in DIO mice affects adipose tissue macrophage accumulation and
      M2 phenotype. Our study identifies Stat3 in VAT-resident T cells as an important
      mediator and direct target for regulating adipose tissue inflammation, DIO, and
      its associated metabolic dysfunctions. 

PMID- 23878228
TI  - Pattern reorganization occurs independently of cell division during Drosophila
      wing disc regeneration in situ.
AB  - One of the most intriguing problems in developmental biology is how an organism
      can replace missing organs or portions of its body after injury. This capacity,
      known as regeneration, is conserved across different phyla. The imaginal discs of
      Drosophila melanogaster provide a particularly well-characterized model for
      analyzing regeneration. We have developed a unique method to study organ
      regeneration under physiological conditions using the imaginal discs of
      Drosophila. Using this method, we revisited different aspects of organ
      regeneration. The results presented in this report suggest that during the
      initial stages of regeneration, different processes occur, including wound
      healing, a temporary loss of markers of cell-fate commitment, and pattern
      reorganization. We present evidence indicating that all of these processes occur
      even when cell division has been arrested. Our data also suggested that Wingless
      is not required during the early stages of disc regeneration. 

PMID- 23878229
TI  - Convergence of auxin and gibberellin signaling on the regulation of the GATA
      transcription factors GNC and GNL in Arabidopsis thaliana.
AB  - Plant growth is regulated by a complex network of signaling events. Points of
      convergence for the signaling cross-talk between the phytohormones auxin and
      gibberellin (GA), which partly control overlapping processes during plant
      development, are largely unknown. At the cellular level, auxin responses are
      controlled by members of the AUXIN RESPONSE FACTOR (ARF) family of transcription
      factors as well as AUXIN/INDOLE-3-ACETIC ACID INDUCIBLE (AUX/IAA) proteins that
      repress the activity of at least a subset of ARFs. Here, we show that the two
      paralogous GATA transcription factors GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM
      INVOLVED (GNC) and GNC-LIKE (GNL)/CYTOKININ-RESPONSIVE GATA FACTOR1 (CGA1) are
      direct and critical transcription targets downstream from ARF2 in the control of
      greening, flowering time, and senescence. Mutants deficient in the synthesis or
      signaling of the phytohormone GA are also impaired in greening, flowering, and
      senescence, and interestingly, GNC and GNL were previously identified as
      important transcription targets of the GA signaling pathway. In line with a
      critical regulatory role for GNC and GNL downstream from both auxin and GA
      signaling, we show here that the constitutive activation of GA signaling is
      sufficient to suppress arf2 mutant phenotypes through repression of GNC and GNL.
      In addition, we show that GA promotes ARF2 protein abundance through a
      translation-dependent mechanism that could serve to override the autoinhibitory
      negative feedback regulation of ARF2 on its own transcription and thereby further
      promote GA signaling. 

PMID- 23878230
TI  - Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5
      cells.
AB  - Recent evidence indicates there is a role for small membrane vesicles, including
      exosomes, as vehicles for intercellular communication. Exosomes secreted by most
      cell types can mediate transfer of proteins, mRNAs, and microRNAs, but their role
      in the transmission of infectious agents is less established. Recent studies have
      shown that hepatocyte-derived exosomes containing hepatitis C virus (HCV) RNA can
      activate innate immune cells, but the role of exosomes in the transmission of HCV
      between hepatocytes remains unknown. In this study, we investigated whether
      exosomes transfer HCV in the presence of neutralizing antibodies. Purified
      exosomes isolated from HCV-infected human hepatoma Huh7.5.1 cells were shown to
      contain full-length viral RNA, viral protein, and particles, as determined by RT
      PCR, mass spectrometry, and transmission electron microscopy. Exosomes from HCV
      infected cells were capable of transmitting infection to naive human hepatoma
      Huh7.5.1 cells and establishing a productive infection. Even with subgenomic
      replicons, lacking structural viral proteins, exosome-mediated transmission of
      HCV RNA was observed. Treatment with patient-derived IgGs showed a variable
      degree of neutralization of exosome-mediated infection compared with free virus.
      In conclusion, this study showed that hepatic exosomes can transmit productive
      HCV infection in vitro and are partially resistant to antibody neutralization.
      This discovery sheds light on neutralizing antibodies resistant to HCV
      transmission by exosomes as a potential immune evasion mechanism. 

PMID- 23878231
TI  - Bispecific antibodies directed to CD4 domain 2 and HIV envelope exhibit
      exceptional breadth and picomolar potency against HIV-1.
AB  - In the absence of an effective HIV-1 vaccine, passive immunization using broadly
      neutralizing Abs or Ab-like molecules could provide an alternative to the daily
      administration of oral antiretroviral agents that has recently shown promise as
      preexposure prophylaxis. Currently, no single broadly neutralizing Ab (bNAb) or
      combination of bNAbs neutralizes all HIV-1 strains at practically achievable
      concentrations in vivo. To address this problem, we created bispecific Abs that
      combine the HIV-1 inhibitory activity of ibalizumab (iMab), a humanized mAb
      directed to domain 2 of human CD4, with that of anti-gp120 bNAbs. These
      bispecific bNAbs (BibNAbs) exploit iMab's potent anti-HIV-1 activity and
      demonstrated clinical efficacy and safety to anchor and thereby concentrate a
      second broadly neutralizing agent at the site of viral entry. Two BibNabs, PG9
      iMab and PG16-iMab, exhibit exceptional breadth and potency, neutralizing 100% of
      the 118 viruses tested at low picomolar concentrations, including viruses
      resistant to both parental mAbs. The enhanced potency of these BibNAbs was
      entirely dependent on CD4 anchoring, not on membrane anchoring per se, and
      required optimal Ab geometry and linker length. We propose that iMab-based
      BibNAbs, such as PG9-iMab and PG16-iMab, are promising candidates for passive
      immunization to prevent HIV-1 infection. 

PMID- 23878232
TI  - Large Pt anomaly in the Greenland ice core points to a cataclysm at the onset of
      Younger Dryas.
AB  - One explanation of the abrupt cooling episode known as the Younger Dryas (YD) is
      a cosmic impact or airburst at the YD boundary (YDB) that triggered cooling and
      resulted in other calamities, including the disappearance of the Clovis culture
      and the extinction of many large mammal species. We tested the YDB impact
      hypothesis by analyzing ice samples from the Greenland Ice Sheet Project 2
      (GISP2) ice core across the Bolling-Allerod/YD boundary for major and trace
      elements. We found a large Pt anomaly at the YDB, not accompanied by a prominent
      Ir anomaly, with the Pt/Ir ratios at the Pt peak exceeding those in known
      terrestrial and extraterrestrial materials. Whereas the highly fractionated Pt/Ir
      ratio rules out mantle or chondritic sources of the Pt anomaly, it does not allow
      positive identification of the source. Circumstantial evidence such as very high,
      superchondritic Pt/Al ratios associated with the Pt anomaly and its timing,
      different from other major events recorded on the GISP2 ice core such as well
      understood sulfate spikes caused by volcanic activity and the ammonium and
      nitrate spike due to the biomass destruction, hints for an extraterrestrial
      source of Pt. Such a source could have been a highly differentiated object like
      an Ir-poor iron meteorite that is unlikely to result in an airburst or trigger
      wide wildfires proposed by the YDB impact hypothesis. 

PMID- 23878233
TI  - Unique insights into maternal mitochondrial inheritance in mice.
AB  - In animals, mtDNA is always transmitted through the female and this is termed
      "maternal inheritance." Recently, autophagy was reported to be involved in
      maternal inheritance by elimination of paternal mitochondria and mtDNA in
      Caenorhabditis elegans; moreover, by immunofluorescence, P62 and LC3 proteins
      were also found to colocalize to sperm mitochondria after fertilization in mice.
      Thus, it has been speculated that autophagy may be an evolutionary conserved
      mechanism for paternal mitochondrial elimination. However, by using two
      transgenic mouse strains, one bearing GFP-labeled autophagosomes and the other
      bearing red fluorescent protein-labeled mitochondria, we demonstrated that
      autophagy did not participate in the postfertilization elimination of sperm
      mitochondria in mice. Although P62 and LC3 proteins congregated to sperm
      mitochondria immediately after fertilization, sperm mitochondria were not
      engulfed and ultimately degraded in lysosomes until P62 and LC3 proteins
      disengaged from sperm mitochondria. Instead, sperm mitochondria unevenly
      distributed in blastomeres during cleavage and persisted in several cells until
      the morula stages. Furthermore, by using single sperm mtDNA PCR, we observed that
      most motile sperm that had reached the oviduct for fertilization had eliminated
      their mtDNA, leaving only vacuolar mitochondria. However, if sperm with remaining
      mtDNA entered the zygote, mtDNA was not eliminated and could be detected in
      newborn mice. Based on these results, we conclude that, in mice, maternal
      inheritance of mtDNA is not an active process of sperm mitochondrial and mtDNA
      elimination achieved through autophagy in early embryos, but may be a passive
      process as a result of prefertilization sperm mtDNA elimination and uneven
      mitochondrial distribution in embryos. 

PMID- 23878234
TI  - Inverse Gillespie for inferring stochastic reaction mechanisms from intermittent
      samples.
AB  - Gillespie stochastic simulation is used extensively to investigate stochastic
      phenomena in many fields, ranging from chemistry to biology to ecology. The
      inverse problem, however, has remained largely unsolved: How to reconstruct the
      underlying reactions de novo from sparse observations. A key challenge is that
      often only aggregate concentrations, proportional to the population numbers, are
      observable intermittently. We discovered that under specific assumptions, the set
      of relative population updates in phase space forms a convex polytope whose
      vertices are indicative of the dominant underlying reactions. We demonstrate the
      validity of this simple principle by reconstructing stochastic models (reaction
      structure plus propensities) from a variety of simulated and experimental
      systems, where hundreds and even thousands of reactions may be occurring in
      between observations. In some cases, the inferred models provide mechanistic
      insight. This principle can lead to the understanding of a broad range of
      phenomena, from molecular biology to population ecology. 

PMID- 23878235
TI  - Ca2+ release-activated Ca2+ channel blockade as a potential tool in
      antipancreatitis therapy.
AB  - Alcohol-related acute pancreatitis can be mediated by a combination of alcohol
      and fatty acids (fatty acid ethyl esters) and is initiated by a sustained
      elevation of the Ca(2+) concentration inside pancreatic acinar cells ([Ca(2+)]i),
      due to excessive release of Ca(2+) stored inside the cells followed by Ca(2+)
      entry from the interstitial fluid. The sustained [Ca(2+)]i elevation activates
      intracellular digestive proenzymes resulting in necrosis and inflammation. We
      tested the hypothesis that pharmacological blockade of store-operated or Ca(2+)
      release-activated Ca(2+) channels (CRAC) would prevent sustained elevation of
      [Ca(2+)]i and therefore protease activation and necrosis. In isolated mouse
      pancreatic acinar cells, CRAC channels were activated by blocking Ca(2+) ATPase
      pumps in the endoplasmic reticulum with thapsigargin in the absence of external
      Ca(2+). Ca(2+) entry then occurred upon admission of Ca(2+) to the extracellular
      solution. The CRAC channel blocker developed by GlaxoSmithKline, GSK-7975A,
      inhibited store-operated Ca(2+) entry in a concentration-dependent manner within
      the range of 1 to 50 MUM (IC50 = 3.4 MUM), but had little or no effect on the
      physiological Ca(2+) spiking evoked by acetylcholine or cholecystokinin.
      Palmitoleic acid ethyl ester (100 MUM), an important mediator of alcohol-related
      pancreatitis, evoked a sustained elevation of [Ca(2+)]i, which was markedly
      reduced by CRAC blockade. Importantly, the palmitoleic acid ethyl ester-induced
      trypsin and protease activity as well as necrosis were almost abolished by
      blocking CRAC channels. There is currently no specific treatment of pancreatitis,
      but our data show that pharmacological CRAC blockade is highly effective against
      toxic [Ca(2+)]i elevation, necrosis, and trypsin/protease activity and therefore
      has potential to effectively treat pancreatitis. 

PMID- 23878236
TI  - Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity.
AB  - Sick sinus syndrome and atrioventricular block are common clinical problems,
      often necessitating permanent pacemaker placement, yet the pathophysiology of
      these conditions remains poorly understood. Here we show that Transient Receptor
      Potential Melastatin 7 (TRPM7), a divalent-permeant channel-kinase of unknown
      function, is highly expressed in embryonic myocardium and sinoatrial node (SAN)
      and is required for cardiac automaticity in these specialized tissues. TRPM7
      disruption in vitro, in cultured embryonic cardiomyocytes, significantly reduces
      spontaneous Ca(2+) transient firing rates and is associated with robust down
      regulation of Hcn4, Cav3.1, and SERCA2a mRNA. TRPM7 knockdown in zebrafish,
      global murine cardiac Trpm7 deletion (KO(alphaMHC-Cre)), and tamoxifen-inducible
      SAN restricted Trpm7 deletion (KO(HCN4-CreERT2)) disrupts cardiac automaticity in
      vivo. Telemetered and sedated KO(alphaMHC-Cre) and KO(HCN4-CreERT2) mice show
      episodes of sinus pauses and atrioventricular block. Isolated SAN from
      KO(alphaMHC-Cre) mice exhibit diminished Ca(2+) transient firing rates with a
      blunted diastolic increase in Ca(2+). Action potential firing rates are
      diminished owing to slower diastolic depolarization. Accordingly, Hcn4 mRNA and
      the pacemaker current, I(f), are diminished in SAN from both KO(alphaMHC-Cre) and
      KO(HCN4-CreERT2) mice. Moreover, heart rates of KO(alphaMHC-Cre) mice are less
      sensitive to the selective I(f) blocker ivabradine, and acute application of the
      recently identified TRPM7 blocker FTY720 has no effect on action potential firing
      rates of wild-type SAN cells. We conclude that TRPM7 influences diastolic
      membrane depolarization and automaticity in SAN indirectly via regulation of Hcn4
      expression.

PMID- 23878237
TI  - Capturing the mutational landscape of the beta-lactamase TEM-1.
AB  - Adaptation proceeds through the selection of mutations. The distribution of
      mutant fitness effect and the forces shaping this distribution are therefore keys
      to predict the evolutionary fate of organisms and their constituents such as
      enzymes. Here, by producing and sequencing a comprehensive collection of 10,000
      mutants, we explore the mutational landscape of one enzyme involved in the spread
      of antibiotic resistance, the beta-lactamase TEM-1. We measured mutation impact
      on the enzyme activity through the estimation of amoxicillin minimum inhibitory
      concentration on a subset of 990 mutants carrying a unique missense mutation,
      representing 64% of possible amino acid changes in that protein reachable by
      point mutation. We established that mutation type, solvent accessibility of
      residues, and the predicted effect of mutations on protein stability primarily
      determined alone or in combination changes in minimum inhibitory concentration of
      mutants. Moreover, we were able to capture the drastic modification of the
      mutational landscape induced by a single stabilizing point mutation (M182T) by a
      simple model of protein stability. This work thereby provides an integrated
      framework to study mutation effects and a tool to understand/define better the
      epistatic interactions. 

PMID- 23878238
TI  - Role of methyl-induced polarization in ion binding.
AB  - The chemical property of methyl groups that renders them indispensable to
      biomolecules is their hydrophobicity. Quantum mechanical studies undertaken here
      to understand the effect of point substitutions on potassium (K-) channels
      illustrate quantitatively how methyl-induced polarization also contributes to
      biomolecular function. K- channels regulate transmembrane salt concentration
      gradients by transporting K(+) ions selectively. One of the K(+) binding sites in
      the channel's selectivity filter, the S4 site, also binds Ba(2+) ions, which
      blocks K(+) transport. This inhibitory property of Ba(2+) ions has been vital in
      understanding K-channel mechanism. In most K-channels, the S4 site is composed of
      four threonine amino acids. The K channels that carry serine instead of threonine
      are significantly less susceptible to Ba(2+) block and have reduced stabilities.
      We find that these differences can be explained by the lower polarizability of
      serine compared with threonine, because serine carries one less branched methyl
      group than threonine. A T->S substitution in the S4 site reduces its
      polarizability, which, in turn, reduces ion binding by several kilocalories per
      mole. Although the loss in binding affinity is high for Ba(2+), the loss in K(+)
      binding affinity is also significant thermodynamically, which reduces channel
      stability. These results highlight, in general, how biomolecular function can
      rely on the polarization induced by methyl groups, especially those that are
      proximal to charged moieties, including ions, titratable amino acids, sulfates,
      phosphates, and nucleotides. 

PMID- 23878239
TI  - Impaired complex IV activity in response to loss of LRPPRC function can be
      compensated by mitochondrial hyperfusion.
AB  - Mitochondrial morphology changes in response to various stimuli but the
      significance of this is unclear. In a screen for mutants with abnormal
      mitochondrial morphology, we identified MMA-1, the Caenorhabditis elegans homolog
      of the French Canadian Leigh Syndrome protein LRPPRC (leucine-rich
      pentatricopeptide repeat containing). We demonstrate that reducing mma-1 or
      LRPPRC function causes mitochondrial hyperfusion. Reducing mma-1/LRPPRC function
      also decreases the activity of complex IV of the electron transport chain,
      however without affecting cellular ATP levels. Preventing mitochondrial
      hyperfusion in mma-1 animals causes larval arrest and embryonic lethality.
      Furthermore, prolonged LRPPRC knock-down in mammalian cells leads to
      mitochondrial fragmentation and decreased levels of ATP. These findings indicate
      that in a mma-1/LRPPRC-deficient background, hyperfusion allows mitochondria to
      maintain their functions despite a reduction in complex IV activity. Our data
      reveal an evolutionary conserved mechanism that is triggered by reduced complex
      IV function and that induces mitochondrial hyperfusion to transiently compensate
      for a drop in the activity of the electron transport chain. 

PMID- 23878240
TI  - Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of
      39 residues.
AB  - Nociceptive information is modulated by a large number of endogenous signaling
      agents that change over the course of recovery from injury. This plasticity makes
      understanding regulatory mechanisms involved in descending inhibition of pain
      scientifically and clinically important. Neurons that synthesize the neuropeptide
      TIP39 project to many areas that modulate nociceptive information. These areas
      are enriched in its receptor, the parathyroid hormone 2 receptor (PTH2R). We
      previously found that TIP39 affects several acute nociceptive responses, leading
      us to now investigate its potential role in chronic pain. Following nerve injury,
      both PTH2R and TIP39 knockout mice developed less tactile and thermal
      hypersensitivity than controls and returned to baseline sensory thresholds
      faster. Effects of hindpaw inflammatory injury were similarly decreased in
      knockout mice. Blockade of alpha-2 adrenergic receptors increased the tactile and
      thermal sensitivity of apparently recovered knockout mice, returning it to levels
      of neuropathic controls. Mice with locus coeruleus (LC) area injection of
      lentivirus encoding a secreted PTH2R antagonist had a rapid, alpha-2 reversible,
      apparent recovery from neuropathic injury similar to the knockout mice. Ablation
      of LC area glutamatergic neurons led to local PTH2R-ir loss, and barley lectin
      was transferred from local glutamatergic neurons to GABA interneurons that
      surround the LC. These results suggest that TIP39 signaling modulates sensory
      thresholds via effects on glutamatergic transmission to brainstem GABAergic
      interneurons that innervate noradrenergic neurons. TIP39's normal role may be to
      inhibit release of hypoalgesic amounts of norepinephrine during chronic pain. The
      neuropeptide may help maintain central sensitization, which could serve to
      enhance guarding behavior. 

PMID- 23878241
TI  - Higd-1a interacts with Opa1 and is required for the morphological and functional
      integrity of mitochondria.
AB  - The activity and morphology of mitochondria are maintained by dynamic fusion and
      fission processes regulated by a group of proteins residing in, or attached to,
      their inner and outer membranes. Hypoxia-induced gene domain protein-1a (Higd
      1a)/HIMP1-a/HIG1, a mitochondrial inner membrane protein, plays a role in cell
      survival under hypoxic conditions. In the present study, we showed that Higd-1a
      depletion resulted in mitochondrial fission, depletion of mtDNA, disorganization
      of cristae, and growth retardation. We demonstrated that Higd-1a functions by
      specifically binding to Optic atrophy 1 (Opa1), a key element in fusion of the
      inner membrane. In the absence of Higd-1a, Opa1 was cleaved, resulting in the
      loss of its long isoforms and accumulation of small soluble forms. The small
      forms of Opa1 do not interact with Higd-1a, suggesting that a part of Opa1 in or
      proximal to the membrane is required for that interaction. Opa1 cleavage,
      mitochondrial fission, and cell death induced by dissipation of the mitochondrial
      membrane potential were significantly inhibited by ectopic expression of Higd-1a.
      Furthermore, growth inhibition due to Higd-1a depletion could be overcome by
      overexpression of a noncleavable form of Opa1. Collectively, our observations
      demonstrate that Higd-1a inhibits Opa1 cleavage and is required for mitochondrial
      fusion by virtue of its interaction with Opa1. 

PMID- 23878242
TI  - The case for distributed irrigation as a development priority in sub-Saharan
      Africa.
AB  - Distributed irrigation systems are those in which the water access (via pump or
      human power), distribution (via furrow, watering can, sprinkler, drip lines,
      etc.), and use all occur at or near the same location. Distributed systems are
      typically privately owned and managed by individuals or groups, in contrast to
      centralized irrigation systems, which tend to be publicly operated and involve
      large water extractions and distribution over significant distances for use by
      scores of farmers. Here we draw on a growing body of evidence on smallholder
      farmers, distributed irrigation systems, and land and water resource availability
      across sub-Saharan Africa (SSA) to show how investments in distributed
      smallholder irrigation technologies might be used to (i) use the water sources of
      SSA more productively, (ii) improve nutritional outcomes and rural development
      throughout SSA, and (iii) narrow the income disparities that permit widespread
      hunger to persist despite aggregate economic advancement. 

PMID- 23878243
TI  - Testing the diffusing boundary model for the helix-coil transition in peptides.
AB  - The dynamics of peptide alpha-helices have been studied extensively for many
      years, and the kinetic mechanism of the helix-coil dynamics has been discussed
      controversially. Recent experimental results have suggested that equilibrium
      helix-coil dynamics are governed by movement of the helix/coil boundary along the
      peptide chain, which leads to slower unfolding kinetics in the helix center
      compared with the helix ends and position-independent helix formation kinetics.
      We tested this diffusion of boundary model in helical peptides of different
      lengths by triplet-triplet energy transfer measurements and compared the data
      with simulations based on a kinetic linear Ising model. The results show that
      boundary diffusion in helical peptides can be described by a classical, Einstein
      type, 1D diffusion process with a diffusion coefficient of 2.7?10(7) (amino
      acids)(2)/s or 6.1?10(-9) cm(2)/s. In helices with a length longer than about 40
      aa, helix unfolding by coil nucleation in a helical region occurs frequently in
      addition to boundary diffusion. Boundary diffusion is slowed down by helix
      stabilizing capping motifs at the helix ends in agreement with predictions from
      the kinetic linear Ising model. We further tested local and nonlocal effects of
      amino acid replacements on helix-coil dynamics. Single amino acid replacements
      locally affect folding and unfolding dynamics with a phif-value of 0.35, which
      shows that interactions leading to different helix propensities for different
      amino acids are already partially present in the transition state for helix
      formation. Nonlocal effects of amino acid replacements only influence helix
      unfolding (phif = 0) in agreement with a diffusing boundary mechanism.

PMID- 23878246
TI  - QnAs with Lynn M. Riddiford. Interview by Sujata Gupta.

PMID- 23878245
TI  - Reactive nitrogen species regulate autophagy through ATM-AMPK-TSC2-mediated
      suppression of mTORC1.
AB  - Reactive intermediates such as reactive nitrogen species play essential roles in
      the cell as signaling molecules but, in excess, constitute a major source of
      cellular damage. We found that nitrosative stress induced by steady-state nitric
      oxide (NO) caused rapid activation of an ATM damage-response pathway leading to
      downstream signaling by this stress kinase to LKB1 and AMPK kinases, and
      activation of the TSC tumor suppressor. As a result, in an ATM-, LKB1-, TSC
      dependent fashion, mTORC1 was repressed, as evidenced by decreased
      phosphorylation of S6K, 4E-BP1, and ULK1, direct targets of the mTORC1 kinase.
      Decreased ULK1 phosphorylation by mTORC1 at S757 and activation of AMPK to
      phosphorylate ULK1 at S317 in response to nitrosative stress resulted in
      increased autophagy: the LC3-II/LC3-I ratio increased as did GFP-LC3 puncta and
      acidic vesicles; p62 levels decreased in a lysosome-dependent manner, confirming
      an NO-induced increase in autophagic flux. Induction of autophagy by NO
      correlated with loss of cell viability, suggesting that, in this setting,
      autophagy was functioning primarily as a cytotoxic response to excess nitrosative
      stress. These data identify a nitrosative-stress signaling pathway that engages
      ATM and the LKB1 and TSC2 tumor suppressors to repress mTORC1 and regulate
      autophagy. As cancer cells are particularly sensitive to nitrosative stress,
      these data open another path for therapies capitalizing on the ability of
      reactive nitrogen species to induce autophagy-mediated cell death. 

PMID- 23878244
TI  - Rapid and robust signaling in the CsrA cascade via RNA-protein interactions and
      feedback regulation.
AB  - Bacterial survival requires the rapid propagation of signals through gene
      networks during stress, but how this is achieved is not well understood. This
      study systematically characterizes the signaling dynamics of a cascade of RNA
      protein interactions in the CsrA system, which regulates stress responses and
      biofilm formation in Escherichia coli. Noncoding RNAs are at the center of the
      CsrA system; target mRNAs are bound by CsrA proteins that inhibit their
      translation, CsrA proteins are sequestered by CsrB noncoding RNAs, and the
      degradation of CsrB RNAs is increased by CsrD proteins. Here, we show using in
      vivo experiments and quantitative modeling that the CsrA system integrates three
      strategies to achieve rapid and robust signaling. These strategies include: (i)
      the sequestration of stable proteins by noncoding RNAs, which rapidly inactivates
      protein activity; (ii) the degradation of stable noncoding RNAs, which enables
      their rapid removal; and (iii) a negative-feedback loop created by CsrA
      repression of CsrD production, which reduces the time for the system to achieve
      steady state. We also demonstrate that sequestration in the CsrA system results
      in signaling that is robust to growth rates because it does not rely on the slow
      dilution of molecules via cell division; therefore, signaling can occur even
      during growth arrest induced by starvation or antibiotic treatment. 

PMID- 23878247
TI  - Context-dependent hierarchies in pigeons.
AB  - Hierarchical organization is widespread in the societies of humans and other
      animals, both in social structure and in decision-making contexts. In the case of
      collective motion, the majority of case studies report that dominant individuals
      lead group movements, in agreement with the common conflation of the terms
      "dominance" and "leadership." From a theoretical perspective, if social
      relationships influence interactions during collective motion, then social
      structure could also affect leadership in large, swarm-like groups, such as fish
      shoals and bird flocks. Here we use computer-vision-based methods and miniature
      GPS tracking to study, respectively, social dominance and in-flight leader
      follower relations in pigeons. In both types of behavior we find hierarchically
      structured networks of directed interactions. However, instead of being
      conflated, dominance and leadership hierarchies are completely independent of
      each other. Although dominance is an important aspect of variation among pigeons,
      correlated with aggression and access to food, our results imply that the stable
      leadership hierarchies in the air must be based on a different set of individual
      competences. In addition to confirming the existence of independent and context
      specific hierarchies in pigeons, we succeed in setting out a robust, scalable
      method for the automated analysis of dominance relationships, and thus of social
      structure, applicable to many species. Our results, as well as our methods, will
      help to incorporate the broader context of animal social organization into the
      study of collective behavior. 

PMID- 23878248
TI  - Pds5 promotes and protects cohesin acetylation.
AB  - Cohesin's Smc1 and Smc3 subunits form V-shaped heterodimers, the nucleotide
      binding domains (NBDs) of which bind the C- and N-terminal domains, respectively,
      of the alpha-kleisin subunit, forming a large tripartite ring within in which
      sister DNAs are entrapped, and thereby held together (sister chromatid cohesion).
      During replication, establishment of stable cohesion is dependent on Eco1
      mediated acetylation of Smc3's NBD, which is thought to prevent dissociation of
      alpha-kleisin from Smc3, thereby locking shut a "DNA exit gate." How Scc3 and
      Pds5, regulatory subunits bound to alpha-kleisin, regulate cohesion establishment
      and maintenance is poorly understood. We show here that by binding to alpha
      kleisin adjacent to its Smc3 nucleotide binding N-terminal domain, Pds5 not only
      promotes cohesin's release from chromatin but also mediates de novo acetylation
      of Smc3 by Eco1 during S phase and subsequently prevents de-acetylation by the
      deacetylase Hos1/HDAC8. By first promoting cohesin's release from chromosomes and
      subsequently creating and guarding the chemical modification responsible for
      blocking release, Pds5 enables chromosomal cohesin to switch during S phase from
      a state of high turnover to one capable of tenaciously holding sister chromatids
      together for extended periods of time, a duality that has hitherto complicated
      analysis of this versatile cohesin subunit. 

PMID- 23878249
TI  - Adult pallium transcriptomes surprise in not reflecting predicted homologies
      across diverse chicken and mouse pallial sectors.
AB  - The thorniest problem in comparative neurobiology is the identification of the
      particular brain region of birds and reptiles that corresponds to the mammalian
      neocortex [Butler AB, Reiner A, Karten HJ (2011) Ann N Y Acad Sci 1225:14-27;
      Wang Y, Brzozowska-Prechtl A, Karten HJ (2010) Proc Natl Acad Sci USA
      107(28):12676-12681]. We explored which genes are actively transcribed in the
      regions of controversial ancestry in a representative bird (chicken) and mammal
      (mouse) at adult stages. We conducted four analyses comparing the expression
      patterns of their 5,130 most highly expressed one-to-one orthologous genes that
      considered global patterns of expression specificity, strong gene markers, and
      coexpression networks. Our study demonstrates transcriptomic divergence,
      plausible convergence, and, in two exceptional cases, conservation between
      specialized avian and mammalian telencephalic regions. This large-scale study
      potentially resolves the complex relationship between developmental homology and
      functional characteristics on the molecular level and settles long-standing
      evolutionary debates. 

PMID- 23878250
TI  - Sulfatase-activated fluorophores for rapid discrimination of mycobacterial
      species and strains.
AB  - Most current diagnostic tests for tuberculosis do not reveal the species or
      strain of pathogen causing pulmonary infection, which can lead to inappropriate
      treatment regimens and the spread of disease. Here, we report an assay for
      mycobacterial strain assignment based on genetically conserved mycobacterial
      sulfatases. We developed a sulfatase-activated probe, 7-hydroxy-9H-(1,3-dichloro
      9,9-dimethylacridin-2-one)-sulfate, that detects enzyme activity in native
      protein gels, allowing the rapid detection of sulfatases in mycobacterial
      lysates. This assay revealed that mycobacterial strains have distinct sulfatase
      fingerprints that can be used to judge both the species and lineage. Our results
      demonstrate the potential of enzyme-activated probes for rapid pathogen
      discrimination for infectious diseases. 

PMID- 23878251
TI  - Oscillatory activity in the monkey hippocampus during visual exploration and
      memory formation.
AB  - Primates explore the visual world through the use of saccadic eye movements.
      Neuronal activity in the hippocampus, a structure known to be essential for
      memory, is modulated by this saccadic activity, but the relationship between
      visual exploration through saccades and memory formation is not well understood.
      Here, we identify a link between theta-band (3-12 Hz) oscillatory activity in the
      hippocampus and saccadic activity in monkeys performing a recognition memory
      task. As monkeys freely explored novel images, saccades produced a theta-band
      phase reset, and the reliability of this phase reset was predictive of subsequent
      recognition. In addition, enhanced theta-band power before stimulus onset
      predicted stronger stimulus encoding. Together, these data suggest that
      hippocampal theta-band oscillations act in concert with active exploration in the
      primate and possibly serve to establish the optimal conditions for stimulus
      encoding. 

PMID- 23878257
TI  - Resilience of river flow regimes.
AB  - Landscape and climate alterations foreshadow global-scale shifts of river flow
      regimes. However, a theory that identifies the range of foreseen impacts on
      streamflows resulting from inhomogeneous forcings and sensitivity gradients
      across diverse regimes is lacking. Here, we derive a measurable index embedding
      climate and landscape attributes (the ratio of the mean interarrival of
      streamflow-producing rainfall events and the mean catchment response time) that
      discriminates erratic regimes with enhanced intraseasonal streamflow variability
      from persistent regimes endowed with regular flow patterns. Theoretical and
      empirical data show that erratic hydrological regimes typical of rivers with low
      mean discharges are resilient in that they hold a reduced sensitivity to climate
      fluctuations. The distinction between erratic and persistent regimes provides a
      robust framework for characterizing the hydrology of freshwater ecosystems and
      improving water management strategies in times of global change. 

PMID- 23878253
TI  - A riboswitch-regulated antisense RNA in Listeria monocytogenes.
AB  - Riboswitches are ligand-binding elements located in 5' untranslated regions of
      messenger RNAs, which regulate expression of downstream genes. In Listeria
      monocytogenes, a vitamin B12-binding (B12) riboswitch was identified, not
      upstream of a gene but downstream, and antisense to the adjacent gene, pocR,
      suggesting it might regulate pocR in a nonclassical manner. In Salmonella
      enterica, PocR is a transcription factor that is activated by 1,2-propanediol,
      and subsequently activates expression of the pdu genes. The pdu genes mediate
      propanediol catabolism and are implicated in pathogenesis. As enzymes involved in
      propanediol catabolism require B12 as a cofactor, we hypothesized that the
      Listeria B12 riboswitch might be involved in pocR regulation. Here we demonstrate
      that the B12 riboswitch is transcribed as part of a noncoding antisense RNA,
      herein named AspocR. In the presence of B12, the riboswitch induces
      transcriptional termination, causing aspocR to be transcribed as a short
      transcript. In contrast, in the absence of B12, aspocR is transcribed as a long
      antisense RNA, which inhibits pocR expression. Regulation by AspocR ensures that
      pocR, and consequently the pdu genes, are maximally expressed only when both
      propanediol and B12 are present. Strikingly, AspocR can inhibit pocR expression
      in trans, suggesting it acts through a direct interaction with pocR mRNA.
      Together, this study demonstrates how pocR and the pdu genes can be regulated by
      B12 in bacteria and extends the classical definition of riboswitches from
      elements governing solely the expression of mRNAs to a wider role in controlling
      transcription of noncoding RNAs. 

PMID- 23878254
TI  - Ultradian metabolic rhythm in the diazotrophic cyanobacterium Cyanothece sp. ATCC
      51142.
AB  - The unicellular cyanobacterium Cyanothece sp. American Type Culture Collection
      (ATCC) 51142 is capable of performing oxygenic photosynthesis during the day and
      microoxic nitrogen fixation at night. These mutually exclusive processes are
      possible only by temporal separation by circadian clock or another cellular
      program. We report identification of a temperature-dependent ultradian metabolic
      rhythm that controls the alternating oxygenic and microoxic processes of
      Cyanothece sp. ATCC 51142 under continuous high irradiance and in high CO2
      concentration. During the oxygenic photosynthesis phase, nitrate deficiency
      limited protein synthesis and CO2 assimilation was directed toward glycogen
      synthesis. The carbohydrate accumulation reduced overexcitation of the
      photosynthetic reactions until a respiration burst initiated a transition to
      microoxic N2 fixation. In contrast to the circadian clock, this ultradian period
      is strongly temperature-dependent: 17 h at 27  degrees C, which continuously
      decreased to 10 h at 39  degrees C. The cycle was expressed by an oscillatory
      modulation of net O2 evolution, CO2 uptake, pH, fluorescence emission, glycogen
      content, cell division, and culture optical density. The corresponding ultradian
      modulation was also observed in the transcription of nitrogenase-related nifB and
      nifH genes and in nitrogenase activities. We propose that the control by the
      newly identified metabolic cycle adds another rhythmic component to the circadian
      clock that reflects the true metabolic state depending on the actual temperature,
      irradiance, and CO2 availability. 

PMID- 23878258
TI  - Recent burning of boreal forests exceeds fire regime limits of the past 10,000
      years.
AB  - Wildfire activity in boreal forests is anticipated to increase dramatically, with
      far-reaching ecological and socioeconomic consequences. Paleorecords are
      indispensible for elucidating boreal fire regime dynamics under changing climate,
      because fire return intervals and successional cycles in these ecosystems occur
      over decadal to centennial timescales. We present charcoal records from 14 lakes
      in the Yukon Flats of interior Alaska, one of the most flammable ecoregions of
      the boreal forest biome, to infer causes and consequences of fire regime change
      over the past 10,000 y. Strong correspondence between charcoal-inferred and
      observational fire records shows the fidelity of sedimentary charcoal records as
      archives of past fire regimes. Fire frequency and area burned increased ~6,000
      3,000 y ago, probably as a result of elevated landscape flammability associated
      with increased Picea mariana in the regional vegetation. During the Medieval
      Climate Anomaly (MCA; ~1,000-500 cal B.P.), the period most similar to recent
      decades, warm and dry climatic conditions resulted in peak biomass burning, but
      severe fires favored less-flammable deciduous vegetation, such that fire
      frequency remained relatively stationary. These results suggest that boreal
      forests can sustain high-severity fire regimes for centuries under warm and dry
      conditions, with vegetation feedbacks modulating climate-fire linkages. The
      apparent limit to MCA burning has been surpassed by the regional fire regime of
      recent decades, which is characterized by exceptionally high fire frequency and
      biomass burning. This extreme combination suggests a transition to a unique
      regime of unprecedented fire activity. However, vegetation dynamics similar to
      feedbacks that occurred during the MCA may stabilize the fire regime, despite
      additional warming. 

PMID- 23878260
TI  - Structural and mechanistic insights into VEGF receptor 3 ligand binding and
      activation.
AB  - Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are key
      drivers of blood and lymph vessel formation in development, but also in several
      pathological processes. VEGF-C signaling through VEGFR-3 promotes
      lymphangiogenesis, which is a clinically relevant target for treating lymphatic
      insufficiency and for blocking tumor angiogenesis and metastasis. The
      extracellular domain of VEGFRs consists of seven Ig homology domains; domains 1-3
      (D1-3) are responsible for ligand binding, and the membrane-proximal domains 4-7
      (D4-7) are involved in structural rearrangements essential for receptor
      dimerization and activation. Here we analyzed the crystal structures of VEGF-C in
      complex with VEGFR-3 domains D1-2 and of the VEGFR-3 D4-5 homodimer. The
      structures revealed a conserved ligand-binding interface in D2 and a unique
      mechanism for VEGFR dimerization and activation, with homotypic interactions in
      D5. Mutation of the conserved residues mediating the D5 interaction (Thr446 and
      Lys516) and the D7 interaction (Arg737) compromised VEGF-C induced VEGFR-3
      activation. A thermodynamic analysis of VEGFR-3 deletion mutants showed that D3,
      D4-5, and D6-7 all contribute to ligand binding. A structural model of the VEGF
      C/VEGFR-3 D1-7 complex derived from small-angle X-ray scattering data is
      consistent with the homotypic interactions in D5 and D7. Taken together, our data
      show that ligand-dependent homotypic interactions in D5 and D7 are essential for
      VEGFR activation, opening promising possibilities for the design of VEGFR
      specific drugs. 

PMID- 23878262
TI  - In vivo synaptic recovery following optogenetic hyperstimulation.
AB  - Local recycling of synaptic vesicles (SVs) allows neurons to sustain transmitter
      release. Extreme activity (e.g., during seizure) may exhaust synaptic
      transmission and, in vitro, induces bulk endocytosis to recover SV membrane and
      proteins; how this occurs in animals is unknown. Following optogenetic
      hyperstimulation of Caenorhabditis elegans motoneurons, we analyzed synaptic
      recovery by time-resolved behavioral, electrophysiological, and ultrastructural
      assays. Recovery of docked SVs and of evoked-release amplitudes (indicating
      readily-releasable pool refilling) occurred within ~8-20 s (tau = 9.2 s and tau =
      11.9 s), whereas locomotion recovered only after ~60 s (tau = 20 s). During ~11-s
      stimulation, 50- to 200-nm noncoated vesicles ("100nm vesicles") formed, which
      disappeared ~8 s poststimulation, likely representing endocytic intermediates
      from which SVs may regenerate. In endophilin, synaptojanin, and dynamin mutants,
      affecting endocytosis and vesicle scission, resolving 100nm vesicles was delayed
      (>20 s). In dynamin mutants, 100nm vesicles were abundant and persistent,
      sometimes continuous with the plasma membrane; incomplete budding of smaller
      vesicles from 100nm vesicles further implicates dynamin in regenerating SVs from
      bulk-endocytosed vesicles. Synaptic recovery after exhaustive activity is slow,
      and different time scales of recovery at ultrastructural, physiological, and
      behavioral levels indicate multiple contributing processes. Similar processes may
      jointly account for slow recovery from acute seizures also in higher animals. 

PMID- 23878263
TI  - Shear stress activation of nuclear receptor PXR in endothelial detoxification.
AB  - Endothelial cells (ECs) are constantly exposed to xenobiotics and endobiotics or
      their metabolites, which perturb EC function, as well as to shear stress, which
      plays a crucial role in vascular homeostasis. Pregnane X receptor (PXR) is a
      nuclear receptor and a key regulator of the detoxification of xeno- and
      endobiotics. Here we show that laminar shear stress (LSS), the atheroprotective
      flow, activates PXR in ECs, whereas oscillatory shear stress, the atheroprone
      flow, suppresses PXR. LSS activation of PXR in cultured ECs led to the increased
      expression of a PXR target gene, multidrug resistance 1 (MDR1). An in vivo study
      using rats showed that the expression of MDR1 was significantly higher in the
      endothelium from the descending thoracic aorta, where flow is mostly laminar,
      than from the inner curvature of aortic arch, where flow is disturbed.
      Functionally, LSS-activated PXR protects ECs from apoptosis triggered by
      doxorubicin via the induction of MDR1 and other detoxification genes. PXR also
      suppressed the expression of proinflammatory adhesion molecules and monocyte
      adhesion in response to TNF-alpha and lipopolysaccharide. Overexpression of a
      constitutively active PXR in rat carotid arteries potently attenuated
      proinflammatory responses. In addition, cDNA microarray revealed a large number
      of the PXR-activated endothelial genes whose products are responsible for major
      steps of detoxification, including phase I and II metabolizing enzymes and
      transporters. These detoxification genes in ECs are induced by LSS in ECs in a
      PXR-dependent manner. In conclusion, our results indicate that PXR represents a
      flow-activated detoxification system to protect ECs against damage by xeno- and
      endobiotics. 

PMID- 23878265
TI  - Changes in the preferred transition speed with added mass to the foot.
AB  - This study was conducted to investigate whether adding mass to subjects' feet
      affects the preferred transition speed (PTS), and to ascertain whether selected
      swing phase variables (maximum ankle dorsiflexion angular velocity, angular
      acceleration, joint moment, and joint power) are determinants of the PTS, based
      upon four previously established criteria. After the PTS of 24 healthy active
      male subjects was found, using an incremental protocol in loaded (2 kg mass added
      to each shoe) and unloaded (shoes only) conditions, subjects walked at three
      speeds (60%, 80%, and 100% of PTS) and ran at one speed (100% of PTS) on a motor
      driven treadmill while relevant data were collected. The PTS of the unloaded
      condition (2.03 +/- 0.12 m/s) was significantly greater (P < .05) than the PTS of
      the loaded condition (1.94 +/- 0.13 m/s). Within both load conditions, all
      dependent variables increased significantly with walking speed, decreased
      significantly when gait changed to a run, and were assumed to provide the
      necessary input to signal a gait transition, fulfilling the requirements of the
      first three criteria, but only ankle angular velocity reached a critical level
      before the transition, satisfying all four criteria to be considered a
      determinant of the PTS. 

PMID- 23878264
TI  - The effects of walking speed on tibiofemoral loading estimated via
      musculoskeletal modeling.
AB  - Net muscle moments (NMMs) have been used as proxy measures of joint loading, but
      musculoskeletal models can estimate contact forces within joints. The purpose of
      this study was to use a musculoskeletal model to estimate tibiofemoral forces and
      to examine the relationship between NMMs and tibiofemoral forces across walking
      speeds. We collected kinematic, kinetic, and electromyographic data as ten adult
      participants walked on a dual-belt force-measuring treadmill at 0.75, 1.25, and
      1.50 m/s. We scaled a musculoskeletal model to each participant and used OpenSim
      to calculate the NMMs and muscle forces through inverse dynamics and weighted
      static optimization, respectively. We determined tibiofemoral forces from the
      vector sum of intersegmental and muscle forces crossing the knee. Estimated
      tibiofemoral forces increased with walking speed. Peak early-stance compressive
      tibiofemoral forces increased 52% as walking speed increased from 0.75 to 1.50
      m/s, whereas peak knee extension NMMs increased by 168%. During late stance, peak
      compressive tibiofemoral forces increased by 18% as speed increased. Although
      compressive loads at the knee did not increase in direct proportion to NMMs,
      faster walking resulted in greater compressive forces during weight acceptance
      and increased compressive and anterior/posterior tibiofemoral loading rates in
      addition to a greater abduction NMM. 

PMID- 23878269
TI  - Relationship between tibial acceleration and proximal anterior tibia shear force
      across increasing jump distance.
AB  - Proximal anterior tibia shear force is a direct loading mechanism of the anterior
      cruciate ligament (ACL) and is a contributor to ACL strain during injury.
      Measurement of this force during competition may provide insight into risk
      factors for ACL injury. Accelerometers may be capable of measuring tibial
      acceleration during competition. The purpose of this study was to examine the
      relationship between acceleration measured by a tibia-mounted accelerometer and
      proximal anterior tibia shear force as measured through inverse dynamics and peak
      posterior ground reaction forces during two leg stop-jump tasks. Nineteen healthy
      male subjects performed stop-jump tasks across increasing jump distances.
      Correlation coefficients were calculated to determine if a relationship exists
      between accelerometer data and proximal anterior tibia shear force and peak
      posterior ground reaction force. An analysis of variance was performed to compare
      these variables across jump distance. Significant correlations were observed
      between accelerometer data and peak posterior ground reaction force, but none
      between accelerometer data and proximal anterior tibia shear force. All variables
      except peak proximal anterior tibia shear force increased significantly as jump
      distance increased. Overall, results of this study provide initial, positive
      support for the use of accelerometers as a useful tool for future injury
      prevention research. 

PMID- 23878270
TI  - Suzanne Eaton: the beautiful logic of development.

PMID- 23878271
TI  - Timing it right: precise ON/OFF switches for Rho1 and Cdc42 GTPases in
      cytokinesis.
AB  - In many eukaryotes, cytokinesis requires an actomyosin contractile ring that is
      crucial for cell constriction and new membrane organization. Two studies in this
      issue (Onishi et al. 2013. J. Cell Biol. http://dx.doi.org.10.1083/jcb.201302001
      and Atkins et al. 2013. J. Cell Biol. http://dx.doi.org.10.1083/jcb.201301090)
      establish that precise activation and/or inactivation of Rho1 and Cdc42 GTPases
      is important for the correct order and successful completion of events downstream
      of actomyosin ring constriction in budding yeast. 

PMID- 23878272
TI  - Review series: Rab GTPases and membrane identity: causal or inconsequential?
AB  - Rab GTPases are highly conserved components of vesicle trafficking pathways that
      help to ensure the fusion of a vesicle with a specific target organelle membrane.
      Specific regulatory pathways promote kinetic proofreading of membrane surfaces by
      Rab GTPases, and permit accumulation of active Rabs only at the required sites.
      Emerging evidence indicates that Rab activation and inactivation are under
      complex feedback control, suggesting that ultrasensitivity and bistability,
      principles established for other cellular regulatory networks, may also apply to
      Rab regulation. Such systems can promote the rapid membrane accumulation and
      removal of Rabs to create time-limited membrane domains with a unique
      composition, and can explain how Rabs define the identity of vesicle and
      organelle membranes. 

PMID- 23878273
TI  - Systematic characterization of the conformation and dynamics of budding yeast
      chromosome XII.
AB  - Chromosomes architecture is viewed as a key component of gene regulation, but
      principles of chromosomal folding remain elusive. Here we used high-throughput
      live cell microscopy to characterize the conformation and dynamics of the longest
      chromosome of Saccharomyces cerevisiae (XII). Chromosome XII carries the
      ribosomal DNA (rDNA) that defines the nucleolus, a major hallmark of nuclear
      organization. We determined intranuclear positions of 15 loci distributed every
      ~100 kb along the chromosome, and investigated their motion over broad time
      scales (0.2-400 s). Loci positions and motions, except for the rDNA, were
      consistent with a computational model of chromosomes based on tethered polymers
      and with the Rouse model from polymer physics, respectively. Furthermore,
      rapamycin-dependent transcriptional reprogramming of the genome only marginally
      affected the chromosome XII internal large-scale organization. Our comprehensive
      investigation of chromosome XII is thus in agreement with recent studies and
      models in which long-range architecture is largely determined by the physical
      principles of tethered polymers and volume exclusion.

PMID- 23878274
TI  - Inhibition of Cdc42 during mitotic exit is required for cytokinesis.
AB  - The role of Cdc42 and its regulation during cytokinesis is not well understood.
      Using biochemical and imaging approaches in budding yeast, we demonstrate that
      Cdc42 activation peaks during the G1/S transition and during anaphase but drops
      during mitotic exit and cytokinesis. Cdc5/Polo kinase is an important upstream
      cell cycle regulator that suppresses Cdc42 activity. Failure to down-regulate
      Cdc42 during mitotic exit impairs the normal localization of key cytokinesis
      regulators-Iqg1 and Inn1-at the division site, and results in an abnormal septum.
      The effects of Cdc42 hyperactivation are largely mediated by the Cdc42 effector
      p21-activated kinase Ste20. Inhibition of Cdc42 and related Rho guanosine
      triphosphatases may be a general feature of cytokinesis in eukaryotes. 

PMID- 23878275
TI  - Chromatin insulator bodies are nuclear structures that form in response to
      osmotic stress and cell death.
AB  - Chromatin insulators assist in the formation of higher-order chromatin structures
      by mediating long-range contacts between distant genomic sites. It has been
      suggested that insulators accomplish this task by forming dense nuclear foci
      termed insulator bodies that result from the coalescence of multiple protein
      bound insulators. However, these structures remain poorly understood,
      particularly the mechanisms triggering body formation and their role in nuclear
      function. In this paper, we show that insulator proteins undergo a dramatic and
      dynamic spatial reorganization into insulator bodies during osmostress and cell
      death in a high osmolarity glycerol-p38 mitogen-activated protein kinase
      independent manner, leading to a large reduction in DNA-bound insulator proteins
      that rapidly repopulate chromatin as the bodies disassemble upon return to
      isotonicity. These bodies occupy distinct nuclear territories and contain a
      defined structural arrangement of insulator proteins. Our findings suggest
      insulator bodies are novel nuclear stress foci that can be used as a proxy to
      monitor the chromatin-bound state of insulator proteins and provide new insights
      into the effects of osmostress on nuclear and genome organization. 

PMID- 23878276
TI  - Loss of BubR1 acetylation causes defects in spindle assembly checkpoint signaling
      and promotes tumor formation.
AB  - BubR1 acetylation is essential in mitosis. Mice heterozygous for the acetylation
      deficient BubR1 allele (K243R/+) spontaneously developed tumors with massive
      chromosome missegregations. K243R/+ mouse embryonic fibroblasts (MEFs) exhibited
      a weakened spindle assembly checkpoint (SAC) with shortened mitotic timing. The
      generation of the SAC signal was intact, as Mad2 localization to the unattached
      kinetochore (KT) was unaltered; however, because of the premature degradation of
      K243R-BubR1, the mitotic checkpoint complex disassociated prematurely in the
      nocodazole-treated condition, suggesting that maintenance of the SAC is
      compromised. BubR1 acetylation was also required to counteract excessive Aurora B
      activity at the KT for stable chromosome-spindle attachments. The association of
      acetylation-deficient BubR1 with PP2A-B56alpha phosphatase was reduced, and the
      phosphorylated Ndc80 at the KT was elevated in K243R/+ MEFs. In relation, there
      was a marked increase of micronuclei and p53 mutation was frequently detected in
      primary tumors of K243R/+ mice. Collectively, the combined effects of failure in
      chromosome-spindle attachment and weakened SAC cause genetic instability and
      cancer in K243R/+ mice. 

PMID- 23878278
TI  - Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation.
AB  - The membrane remodeling events required for autophagosome biogenesis are still
      poorly understood. Because PX domain proteins mediate membrane remodeling and
      trafficking, we conducted an imaging-based siRNA screen for autophagosome
      formation targeting human PX proteins. The PX-BAR protein SNX18 was identified as
      a positive regulator of autophagosome formation, and its Drosophila melanogaster
      homologue SH3PX1 was found to be required for efficient autophagosome formation
      in the larval fat body. We show that SNX18 is required for recruitment of Atg16L1
      positive recycling endosomes to a perinuclear area and for delivery of Atg16L1-
      and LC3-positive membranes to autophagosome precursors. We identify a direct
      interaction of SNX18 with LC3 and show that the pro-autophagic activity of SNX18
      depends on its membrane binding and tubulation capacity. We also show that the
      function of SNX18 in membrane tubulation and autophagy is negatively regulated by
      phosphorylation of S233. We conclude that SNX18 promotes autophagosome formation
      by virtue of its ability to remodel membranes and provide membrane to forming
      autophagosomes. 

PMID- 23878280
TI  - And the beat goes on...the beat goes on: organization and quasi-periodicity in
      ventricular fibrillation.

PMID- 23878277
TI  - Distinct roles of Rho1, Cdc42, and Cyk3 in septum formation and abscission during
      yeast cytokinesis.
AB  - In yeast and animal cytokinesis, the small guanosine triphosphatase (GTPase)
      Rho1/RhoA has an established role in formation of the contractile actomyosin
      ring, but its role, if any, during cleavage-furrow ingression and abscission is
      poorly understood. Through genetic screens in yeast, we found that either
      activation of Rho1 or inactivation of another small GTPase, Cdc42, promoted
      secondary septum (SS) formation, which appeared to be responsible for abscission.
      Consistent with this hypothesis, a dominant-negative Rho1 inhibited SS formation
      but not cleavage-furrow ingression or the concomitant actomyosin ring
      constriction. Moreover, Rho1 is temporarily inactivated during cleavage-furrow
      ingression; this inactivation requires the protein Cyk3, which binds Rho1
      guanosine diphosphate via its catalytically inactive transglutaminase-like
      domain. Thus, unlike the active transglutaminases that activate RhoA, the
      multidomain protein Cyk3 appears to inhibit activation of Rho1 (and thus SS
      formation), while simultaneously promoting cleavage-furrow ingression through
      primary septum formation. This work suggests a general role for the catalytically
      inactive transglutaminases of fungi and animals, some of which have previously
      been implicated in cytokinesis. 

PMID- 23878279
TI  - Coordinated waves of actomyosin flow and apical cell constriction immediately
      after wounding.
AB  - Epithelial wound healing relies on tissue movements and cell shape changes. Our
      work shows that, immediately after wounding, there was a dramatic cytoskeleton
      remodeling consisting of a pulse of actomyosin filaments that assembled in cells
      around the wound edge and flowed from cell to cell toward the margin of the
      wound. We show that this actomyosin flow was regulated by Diaphanous and ROCK and
      that it elicited a wave of apical cell constriction that culminated in the
      formation of the leading edge actomyosin cable, a structure that is essential for
      wound closure. Calcium signaling played an important role in this process, as its
      intracellular concentration increased dramatically immediately after wounding,
      and down-regulation of transient receptor potential channel M, a stress-activated
      calcium channel, also impaired the actomyosin flow. Lowering the activity of
      Gelsolin, a known calcium-activated actin filament-severing protein, also
      impaired the wound response, indicating that cleaving the existing actin filament
      network is an important part of the cytoskeleton remodeling process. 

PMID- 23878281
TI  - Liver fibrosis: histopathologic and biochemical influences on diagnostic efficacy
      of hepatobiliary contrast-enhanced MR imaging in staging.
AB  - PURPOSE: To evaluate the diagnostic performance of gadoxetic acid-enhanced
      magnetic resonance (MR) imaging in the staging of liver fibrosis in patients with
      diffuse chronic liver diseases (CLDs) and to investigate the factors that may
      influence the results. MATERIALS AND METHODS: With the approval of the Hospital
      Ethics Committee and waiver of the informed consent requirement, data in 102
      patients with histologically proven liver fibrosis (classified according to the
      METAVIR system) of various underlying causes were retrospectively analyzed.
      Patients underwent 3.0-T MR imaging with gadoxetic acid. The signal intensity of
      the liver was defined by using region of interest measurements before contrast
      material injection and in the hepatobiliary phase (20 minutes after contrast
      material administration), and relative enhancement was calculated. Univariate and
      multivariate regression analyses were applied to identify variables associated
      with relative enhancement measurements, and the performance of relative
      enhancement measurements in the staging of liver fibrosis was assessed by using
      area under the receiver operating characteristic curve (AUC) analysis. RESULTS:
      At analysis of the relationship between enhancement measurements and histologic
      parameters, the relative enhancement values correlated strongly with liver
      fibrosis stage (r = -0.65, P < .0001) and moderately with necroinflammatory
      activity grades (r = -0.41, P = .002) and the presence of iron load (r = -0.21, P
      = .05). In multivariate analysis, only liver fibrosis stage independently
      influenced relative enhancement values (P < .001). The measurements performed
      well in the staging of liver fibrosis, with an AUC of 0.81 for stages of F1 or
      greater, 0.82 for stages of F2 or greater, 0.85 for stages of F3 or greater, and
      0.83 for stage F4. Increased aspartate aminotransferase, gammaglutamyl
      transpeptidase, and alkaline phosphatase levels were independent predictors of
      false-negative results. CONCLUSION: The presence of hepatic fibrosis can be
      assessed with good discrimination by using gadoxetic acid-enhanced MR imaging,
      but assessment can be confounded in the setting of abnormal aspartate
      aminotransferase, gammaglutamyl transpeptidase, and alkaline phosphatase levels.

PMID- 23878282
TI  - Measurement of myocardial extracellular volume fraction by using equilibrium
      contrast-enhanced CT: validation against histologic findings.
AB  - PURPOSE: To develop and validate equilibrium contrast material-enhanced computed
      tomography (CT) to measure myocardial extracellular volume (ECV) fraction by
      using a histologic reference standard and to compare equilibrium CT with
      equilibrium contrast-enhanced magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: A local ethics committee approved the study, and all subjects gave fully
      informed written consent. An equilibrium CT protocol was developed using iohexol
      at 300 mg of iodine per milliliter (bolus of 1 mg per kilogram of body weight
      administered at a rate of 3 mL/sec, followed immediately by an infusion of 1.88
      mL/kg per hour with CT imaging before and at 25 minutes after injection of bolus
      of contrast agent) and ECV within the myocardial septum measured using both
      equilibrium CT and equilibrium MR imaging in patients with severe aortic
      stenosis. Biopsy samples of the myocardial septum collected during valve
      replacement surgery were used for histologic quantification of extracellular
      fibrosis with picrosirius red staining. Equilibrium CT- and equilibrium MR
      imaging-derived ECV measurements were compared with histologically quantified
      fibrosis by using Pearson correlation. Agreement between equilibrium CT and
      equilibrium MR imaging was assessed by using Bland-Altman comparison. RESULTS:
      Twenty-three patients (16 male, seven female; mean age, 70.8 years; standard
      deviation, 8.3) were recruited. The mean percentage of histologic fibrosis was
      18% (intersubject range, 5%-40%). There was a significant correlation between
      both equilibrium CT- and equilibrium MR imaging-derived ECV and percentage of
      histologic fibrosis (r = 0.71 [P < .001] and r = 0.84 [P < .0001], respectively).
      Equilibrium CT-derived ECV was significantly correlated to equilibrium MR imaging
      derived ECV (r = 0.73). CONCLUSION: ECV measured by using equilibrium CT in
      patients with aortic stenosis correlates with histologic quantification of
      myocardial fibrosis and with ECV derived by using equilibrium MR imaging.

PMID- 23878283
TI  - Triple-negative and non-triple-negative invasive breast cancer: association
      between MR and fluorine 18 fluorodeoxyglucose PET imaging.
AB  - PURPOSE: To assess the relationship between parameters measured on dynamic
      contrast material-enhanced (DCE) magnetic resonance (MR) imaging and fluorine 18
      fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography
      (CT) in primary invasive breast cancer. MATERIALS AND METHODS: This HIPAA
      compliant study was a retrospective review of medical records and therefore
      approved by the institutional review board without the requirement for informed
      consent. Patients with a diagnosis of invasive breast cancer from January 2005
      through December 2009 who underwent both DCE MR imaging and FDG PET/CT before
      treatment initiation were retrospectively identified. Fractional volumes were
      measured for ranges of signal enhancement ratio (SER) values from DCE MR imaging
      data and compared with maximum standardized uptake values (SUVmax) from FDG
      PET/CT data. Linear regression analysis was performed to clarify the relationship
      between SER and SUVmax, adjusting for tumor size, pathologic grade, and receptor
      status. RESULTS: Analyzed were 117 invasive breast cancers in 117 patients.
      Overall, a higher percentage of high washout kinetics was positively associated
      with SUVmax (1.57% increase in SUVmax per 1% increase in high washout; P = .020),
      and a higher percentage of low plateau kinetics was negatively associated with
      SUVmax (1.19% decrease in SUVmax per 1% increase in low plateau; P = .003). These
      relationships were strongest among triple-negative (TN) tumors (4.34% increase in
      SUVmax per 1% increase in high washout and 2.65% decrease in SUVmax per 1%
      increase in low plateau; P = .018 and .004, respectively). CONCLUSION: In
      invasive breast carcinoma, there is a positive relationship between the
      percentage of high washout and SUVmax and a negative relationship between the
      percentage of low plateau and SUVmax. These results are stronger in TN tumors.
      SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130058/-/DC1.

PMID- 23878284
TI  - Transition zone prostate cancer: incremental value of diffusion-weighted
      endorectal MR imaging in tumor detection and assessment of aggressiveness.
AB  - PURPOSE: To evaluate the incremental value of using diffusion-weighted magnetic
      resonance (MR) imaging in addition to T2-weighted imaging for the detection of
      prostate cancer in the transition zone and the assessment of tumor
      aggressiveness. MATERIALS AND METHODS: This retrospective HIPAA-compliant
      institutional review board-approved study included 156 consecutive patients
      (median age, 59.2 years) who underwent MR imaging before radical prostatectomy.
      Two readers who were blinded to patient data independently recorded their levels
      of suspicion on a five-point scale of the presence of transition zone tumors on
      the basis of T2-weighted imaging alone and then, 4 weeks later, diffusion
      weighted imaging and T2-weighted imaging together. Apparent diffusion
      coefficients (ADCs) were measured in transition zone cancers and glandular and
      stromal benign prostatic hyperplasia. Areas under the receiver operating
      characteristic curves were used to evaluate detection accuracy, and generalized
      linear models were used to test ADC differences between benign and malignant
      prostate regions. Whole-mount step-section histopathologic examination was the
      reference standard. RESULTS: In overall tumor detection, addition of diffusion
      weighted imaging to T2-weighted imaging improved the areas under the receiver
      operating characteristic curves for readers 1 and 2 from 0.60 and 0.60 to 0.75
      and 0.71, respectively, at the patient level (P = .004 for reader 1 and P = .027
      for reader 2) and from 0.64 and 0.63 to 0.73 and 0.68, respectively, at the
      sextant level (P = .001 for reader 1 and P = .100 for reader 2). Least squares
      mean ADCs (* 10(-3) mm(2)/sec) in glandular and stromal benign prostatic
      hyperplasia were 1.44 and 1.09, respectively. Mean ADCs were inversely associated
      with tumor Gleason scores (1.10, 0.98, 0.87, and 0.75 for Gleason scores of 3 +
      3, 3 + 4, 4 + 3, and >= 4 + 4, respectively). CONCLUSION: Use of diffusion
      weighted imaging in addition to T2-weighted imaging improved detection of
      prostate cancer in the transition zone, and tumor ADCs were inversely associated
      with tumor Gleason scores in the transition zone.

PMID- 23878285
TI  - In vivo 39K MR imaging of human muscle and brain.
AB  - PURPOSE: To implement potassium 39 ((39)K) magnetic resonance (MR) imaging with a
      7-T MR imaging system and to evaluate its feasibility for in vivo imaging of
      human muscle and brain. MATERIALS AND METHODS: Three healthy volunteers were
      examined with approval of the ethical review board of Heidelberg University.
      Written informed consent was obtained from all volunteers. Because the available
      7-T MR imaging system did not support (39)K, a frequency conversion scheme was
      developed and connected to the imaging unit. The standard X-nucleus frequency of
      lithium 7 (115 MHz) was converted to the frequency of (39)K at 7 T (14 MHz).
      Relaxation times of healthy thigh muscle and brain tissue were estimated by using
      multiple-echo and inversion-recovery sequences. Data analysis was conducted with
      a nonlinear least squares curve fitting tool. In vivo (39)K MR imaging of healthy
      human thigh muscle and brain was performed. RESULTS: With use of the custom-built
      frequency conversion scheme, (39)K MR imaging is feasible with a commercially
      available 7-T MR imaging system. Nominal spatial resolutions of 8 * 8 * 16 mm(3)
      and 9.5 * 9.5 * 9.5 mm(3) were achieved for human thigh muscle and brain,
      respectively. Acquisition time was 30 minutes for both muscle and brain tissue.
      The measured potassium concentration (uncorrected for fat fraction) of thigh
      muscle tissue (112-124 mmol/L) lies within the expected range. CONCLUSION: In
      vivo (39)K MR imaging in humans can be performed in clinically feasible
      measurement times (approximately 30 minutes) with voxel sizes of approximately 1
      mL.

PMID- 23878287
TI  - Chilaiditi syndrome: a case of missed diagnosis.

PMID- 23878286
TI  - Recurrent glioblastoma: optimum area under the curve method derived from dynamic
      contrast-enhanced T1-weighted perfusion MR imaging.
AB  - PURPOSE: To determine whether the ratio of the initial area under the time-signal
      intensity curve (AUC) (IAUC) to the final AUC--or AUCR--derived from dynamic
      contrast material-enhanced magnetic resonance (MR) imaging can be an imaging
      biomarker for distinguishing recurrent glioblastoma multiforme (GBM) from
      radiation necrosis and to compare the diagnostic accuracy of the AUCR with
      commonly used model-free dynamic contrast-enhanced MR imaging parameters.
      MATERIALS AND METHODS: The institutional review board approved this retrospective
      study and waived the informed consent requirement. Fifty-seven consecutive
      patients with pathologically confirmed recurrent GBM (n = 32) or radiation
      necrosis (n = 25) underwent dynamic contrast-enhanced MR imaging. Histogram
      parameters of the IAUC at 30, 60, and 120 seconds and the AUCR, which included
      the mean value at the higher curve of the bimodal histogram (mAUCR(H)), as well
      as 90th percentile cumulative histogram cutoffs, were calculated and were
      correlated with final pathologic findings. The best predictor for differentiating
      recurrent GBM from radiation necrosis was determined by means of receiver
      operating characteristic (ROC) curve analysis. RESULTS: The demographic data were
      not significantly different between the two patient groups. There were
      statistically significant differences in all of the IAUC and AUCR parameters
      between the recurrent GBM and the radiation necrosis patient groups (P < .05 for
      each). ROC curve analyses showed mAUCR(H) to be the best single predictor of
      recurrent GBM (mAUCR(H) for recurrent GBM = 0.35 +/- 0.11 [standard deviation],
      vs 0.19 +/- 0.17 for radiation necrosis; P < .0001; optimum cutoff, 0.23), with a
      sensitivity of 93.8% and a specificity of 88.0%. CONCLUSION: A bimodal histogram
      analysis of AUCR derived from dynamic contrast-enhanced MR imaging can be a
      potential noninvasive imaging biomarker for differentiating recurrent GBM from
      radiation necrosis. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130016/-/DC1.

PMID- 23878288
TI  - Central giant cell granuloma: a case report.
AB  - Central giant cell granuloma (CGCG) is a relatively uncommon benign bony lesion
      of a variably aggressive nature. Thought to represent a reparative response to
      intrabony haemorrhage and inflammation, CGCG was once regarded as a reactive
      lesion. It is actually an asymptomatic lesion which becomes evident during
      routine radiographic examination or as a result of painless but visible expansion
      of the affected jaw. This paper presents the case of a 4-year-old boy with  CGCG
      in the right mandibular region. 

PMID- 23878289
TI  - A surprise behind a case of winter vomiting virus.
AB  - A 79-year-old man was admitted through the medical take with norovirus gastritis.
      Routine plain chest radiography demonstrated a right coin lesion. CT and
      subsequent positron emission tomography showed a right upper lobe mass consistent
      with primary bronchial carcinoma. The lesion was resected and histology revealed
      a granulomatous necrotising mass without evidence of dysplasia. Meticulous
      investigations for infectious and non-infectious causes of necrotising
      granulomatous diseases were repeatedly negative. His postoperative recovery was
      complicated by a hospital-acquired pneumonia and a pulmonary embolism. CT
      pulmonary angiography showed progression of the previously resected mass and
      repeat biopsy was similar to the initial. A clinical diagnosis of antineutrophil
      cytoplasmic antibody-negative vasculitis without extrapulmonary manifestations
      was made and immunosuppressive therapy was initiated with rapid clinical
      response. 

PMID- 23878290
TI  - Keratinous inclusion cyst of oesophagus: unusual finding.
AB  - Cysts of the oesophagus are unusual findings and they are classified according to
      the embryological site of origin. It may represent inclusion cysts, retention
      cysts and developmental cysts. We present a case of keratinous inclusion cyst of
      the lower oesophagus in a 71-year-old Malay woman who presented with dyspepsia
      and severe epigastric pain. An oesophago-gastro-duodenoscopy demonstrated a
      sliding hiatus hernia with whitish ulcer-like lesion at the lower oesophagus.
      Biopsy from the lesion revealed a keratinous inclusion cyst. The patient was
      given pantoprazole and put on regular follow-up for monitoring any other
      development. 

PMID- 23878291
TI  - Disorder of sex development as a diagnostic clue in the first Spanish known
      newborn with P450 oxidoreductase deficiency.
AB  - We report the first known case of p450 oxidoreductase deficiency (PORD) in a
      Spanish boy who presented ambiguous genitalia at birth as a unique feature. He
      had palpable gonads in the inguinal canal and a normal 46,XY karyotype. Blood
      tests showed increased lanosterol and androgen precursors (17-OH-pregnenolone and
      17-OH-progesterone) and low adrenal androgens (dehydroepiandrosterone and its
      sulfate). Blood pressure and serum electrolytes were normal. As he had low
      testosterone response to human chorionic gonadotropin stimulation but responded
      to exogenous testosterone with phallic growth, male sex was assigned.
      Testosterone/dihydrotestosterone ratio and inhibin B were normal. Adrenal
      insufficiency was detected by corticotropin test. Hydrocortisone replacement
      treatment was administered. Congenital adrenal hyperplasia was ruled out and
      molecular analysis of POR gene showed the missense mutation p.Gly539Arg in
      compound heterozygosity located at splice acceptor site of intron 2 and the
      coding variant p.Gly80Arg. Surgery for cryptorchidism and hypospadias was
      performed. 

PMID- 23878292
TI  - Tracheobronchopathia osteochondroplastica: innocuous but distressing.

PMID- 23878293
TI  - Acute respiratory failure in a rapidly enlarging benign cervical goitre.
AB  - Benign goitres have the potential to reach massive sizes if neglected, but most
      have a protracted course that may or may not present with compressive symptoms.
      We report the case of a 57-year-old man who presented with a rapidly enlarging
      nodular goitre resulting in acute respiratory failure. Endotracheal intubation
      and emergency total thyroidectomy were performed, revealing massive thyroid
      nodules with minimal intrathoracic extension and tracheal erosion. Despite a
      course and clinical findings suggestive of malignant disease, histopathology was
      consistent with a benign multinodular goitre. Several cases of benign goitres
      necessitating endotracheal intubation have been reported. Airway compromise was
      attributed to a significant intrathoracic component, or inciting events such as
      thyroid haemorrhage, pregnancy, radioiodine uptake or major surgery. Obstructive
      symptoms may not correlate well with objective measures of upper airway
      obstruction such as radiographs or flow volume loops. 

PMID- 23878294
TI  - ACE inhibitor-induced intestinal angio-oedema: rare adverse effect of a common
      drug.
AB  - ACE inhibitors are the leading cause of drug-induced angio-oedema in the USA. ACE
      inhibitor-induced intestinal angio-oedema, a much rarer complication of this
      medication, has been reported. The author reports a patient presenting with a 1
      day history of severe abdominal pain. The patient was started on lisinopril 2
      days prior to this presentation. Computer axial tomography (CAT) scan of the
      abdomen demonstrated extensive and marked thickening, and oedema involving the
      duodenum and proximal jejunum associated with significant mesenteric oedema.
      Concerns for visceral angio-oedema and a possible association with lisinopril
      according to the Naranjo algorithm were raised. Lisinopril was discontinued and
      the patient was treated with antihistamines. The patient improved clinically in
      the next 24 h and discharged home with education and documentation of this
      serious allergy. ACE inhibitor-induced visceral angio-oedema is under-reported
      and most often missed resulting in waste of hospital resources towards working up
      this clinical diagnosis. 

PMID- 23878296
TI  - Finishing the picture: problems with public reporting of clinical trials.

PMID- 23878295
TI  - Utility of progranulin and serum leukocyte protease inhibitor as diagnostic and
      prognostic biomarkers in ovarian cancer.
AB  - BACKGROUND: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer
      related death in females and leading gynecologic cause of cancer-related death.
      Despite the identification of a number of serum biomarkers, methods to identify
      early-stage disease and predict prognosis remain scarce. We have evaluated two
      biologically connected serum biomarkers, serum leukocyte protease inhibitor
      (SLPI) and progranulin (PGRN). METHODS: Two-hundred frozen plasma samples were
      acquired from the Mayo Clinic Biospecimen Repository for Ovarian Cancer Research.
      Samples were obtained from 50 patients with benign conditions, 50 with American
      Joint Committee on Cancer (AJCC) stage I and II EOC, and 100 with AJCC stage III
      and IV EOC. Samples were obtained before surgical resection of a mass and were
      analyzed for absolute levels of SLPI and PGRN using ELISA assays. Receiver
      operator characteristic curves were generated for SLPI and PGRN. Median follow-up
      was 48 months. RESULTS: Absolute levels of SLPI were significantly elevated in
      patients with EOC compared with benign disease and predicted the presence of EOC
      (AUC of 0.812; P = 0.04); SLPI remained elevated in the subset of patients with
      normal CA-125. PGRN levels were not significantly increased in patients with
      early-stage or late-stage EOC as a whole, but an increase in PGRN levels was
      associated with decreased overall survival in advanced EOC. CONCLUSIONS: SLPI
      levels are elevated in EOC, and SLPI shows promise as a diagnostic biomarker for
      patients with both elevated and normal CA-125 levels. An increase in PGRN is
      associated with decreased overall survival. IMPACT: SLPI is elevated in EOC and
      warrants investigation in a screening study in women at risk for EOC.

PMID- 23878297
TI  - Time to define high-quality palliative care in oncology.

PMID- 23878298
TI  - Public availability of results of trials assessing cancer drugs in the United
      States.
AB  - PURPOSE: To evaluate to what extent results of completed trials of cancer drugs
      conducted in the United States are publicly available at ClinicalTrials.gov, as
      required by the Food and Drug Administration Amendments Act (FDAAA), or are
      published in journals. METHODS: We searched ClinicalTrials.gov for cancer trials
      governed by the FDAAA: phase II to IV trials assessing drugs in the United States
      with a primary completion date between December 26, 2007, and May 31, 2010. For
      each trial, we also searched PubMed to identify the publication of results. We
      assessed the cumulative percentages of posted or published results over time by
      using the Kaplan-Meier method. RESULTS: We identified 646 trials, including 209
      randomized controlled trials (RCTs). At 12 months after completion of the trials,
      the cumulative percentages of trials with results posted at ClinicalTrials.gov,
      published in journals, and available either at ClinicalTrials.gov or in journals
      were 9% (95% CI, 7% to 11%), 12% (95% CI, 10% to 15%), and 20% (95% CI, 17% to
      23%), respectively, and for RCTs, the percentages were 12% (95% CI, 8% to 16%),
      5% (95% CI, 2% to 8%), and 17% (95% CI, 12% to 22%), respectively. At 36 months,
      these percentages were 31% (95% CI, 28% to 35%), 35% (95% CI, 31% to 39%), and
      55% (95% CI, 51% to 59%), respectively, and for RCTs, they were 38% (95% CI, 31%
      to 45%), 32% (95% CI, 25% to 39%), and 56% (95% CI, 48% to 62%), respectively.
      Public availability of phase III trials was 15% (95% CI, 7% to 23%) at 12 months,
      39% (95% CI, 27% to 49%) at 24 months, and 64% (95% CI, 50% to 73%) at 36 months.
      CONCLUSION: Despite the FDAAA, results for nearly half the trials of cancer drugs
      in the United States were not publicly available 3 years after completion of the
      trials.

PMID- 23878299
TI  - Emil Frei's contributions.

PMID- 23878300
TI  - Re-examining racial disparities in prostate cancer outcomes.

PMID- 23878301
TI  - Respiratory care. Editor's commentary.

PMID- 23878302
TI  - Behind a mask: tricks, pitfalls, and prejudices for noninvasive ventilation.
AB  - It is difficult to exactly date the beginning of mechanical ventilation, but
      there are no doubts that noninvasive ventilation (NIV) was the first method of
      ventilatory support in clinical practice. The technique had a sudden increase in
      popularity, so that it is now considered, according to criteria of evidence-based
      medicine, the first-line treatment for an episode of acute respiratory failure in
      4 pathologies (the Fabulous Four): COPD exacerbation, cardiogenic pulmonary
      edema, pulmonary infiltrates in immunocompromised patients, and in the weaning of
      extubated COPD patients. The so-called emerging applications are those for which
      the evidence has not achieved level A, mainly because the number or sample size
      of the published studies does not allow conclusive meta-analysis. These emerging
      applications are the post-surgical period, palliation of dyspnea, asthma attack,
      obesity hypoventilation syndrome, and to prevent extubation failure. Potentially
      "risky business" uses include for respiratory failure from pandemic diseases and
      ARDS, where probably the "secret" for success is early use. Healthcare is rich in
      evidence-based innovations, yet even when such innovations are implemented
      successfully in one location, they often disseminate slowly, if at all, so their
      clinical use remains limited and heterogeneous. The low rate of NIV use in some
      hospitals relates to lack of knowledge about or experience with NIV, insufficient
      confidence in the technique, lack of NIV equipment, and inadequate funding. But
      NIV use has been increasing around the world, thanks partly to improved
      technologies. The skill and confidence of clinicians in NIV have improved with
      time and experience, but NIV is and should remain a team effort, rather than the
      property of a single local "champion," because, overall, NIV is beautiful! 

PMID- 23878303
TI  - Thinking outside the box: moving the respiratory care profession beyond the
      hospital walls.
AB  - For centuries, hospitals have served as the cornerstone of the United States
      healthcare system. Just like the majority of the general population, the
      respiratory care profession was born inside the hospital walls, just over 6
      decades ago. While the knowledge, skills, and attributes of the respiratory
      therapist are critically necessary in acute care settings, the profession must
      move itself to a stronger position across the entire continuum of care of
      patients with acute and chronic cardiopulmonary diseases within the next several
      years to stay ahead of the curve of healthcare reform. In this paper, based on
      the 28th annual Philip Kittredge Memorial Lecture, I will examine the necessary
      strategies and values that the profession of respiratory care will need to
      successfully embrace to "think outside the box" and move the profession beyond
      the hospital walls for patient- and outcomes-focused, sustainable impact in the
      future healthcare delivery system. 

PMID- 23878304
TI  - What's to be learned from 10 patients in one pediatric ICU?

PMID- 23878305
TI  - A step up for extracorporeal membrane oxygenation: active rehabilitation.

PMID- 23878306
TI  - Has the opportunity gone up in smoke?

PMID- 23878307
TI  - CD28-inducible transcription factor DEC1 is required for efficient autoreactive
      CD4+ T cell response.
AB  - During the initial hours after activation, CD4(+) T cells experience profound
      changes in gene expression. Co-stimulation via the CD28 receptor is required for
      efficient activation of naive T cells. However, the transcriptional consequences
      of CD28 co-stimulation are not completely understood. We performed expression
      microarray analysis to elucidate the effects of CD28 signals on the transcriptome
      of activated T cells. We show that the transcription factor DEC1 is highly
      induced in a CD28-dependent manner upon T cell activation, is involved in
      essential CD4(+) effector T cell functions, and participates in the
      transcriptional regulation of several T cell activation pathways, including a
      large group of CD28-regulated genes. Antigen-specific, DEC1-deficient CD4(+) T
      cells have cell-intrinsic defects in survival and proliferation. Furthermore, we
      found that DEC1 is required for the development of experimental autoimmune
      encephalomyelitis because of its critical role in the production of the
      proinflammatory cytokines GM-CSF, IFN-gamma, and IL-2. Thus, we identify DEC1 as
      a critical transcriptional mediator in the activation of naive CD4(+) T cells
      that is required for the development of a T cell-mediated autoimmune disease. 

PMID- 23878308
TI  - MK5 activates Rag transcription via Foxo1 in developing B cells.
AB  - Foxo1 is a critical, direct regulator of Rag (recombination activating gene)
      transcription during B cell development and is thus essential for the generation
      of a diverse repertoire of antigen receptors. Although Foxo1 regulation has been
      widely studied in many cell types, pathways regulating Foxo1 in B cells have not
      been fully elucidated. By screening a panel of Foxo1 mutants, we identified
      serine 215 on Foxo1 as a novel phosphorylation site that is essential for the
      activation of Rag transcription. Mutation of S215 strongly attenuated
      transactivation of Rag but did not affect most other Foxo1 target genes. We show
      that MK5, a MAPK-activated protein kinase, is a previously unidentified upstream
      regulator of Foxo1. MK5 was necessary and sufficient to activate Rag
      transcription in transformed and primary pro-B cells. Together, our experiments
      show that MK5 positively regulates Rag transcription via phosphorylation of Foxo1
      in developing B cells. 

PMID- 23878310
TI  - Biosimilars in rheumatology: perspective and concerns.

PMID- 23878311
TI  - Osteoarthritis: a progressive disease with changing phenotypes.

PMID- 23878309
TI  - Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by
      lymph node lymphatic sinuses.
AB  - Lymphatic vessels are thought to contribute to metastasis primarily by serving as
      a transportation system. It is widely believed that tumor cells enter lymph nodes
      passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses
      control tumor cell entry into the lymph node, which requires active tumor cell
      migration. In human and mouse tissues, CCL1 protein is detected in lymph node
      lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for
      CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to
      lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or
      CCL1, and recombinant CCL1 promotes migration of CCR8(+) tumor cells. The
      proinflammatory mediators TNF, IL-1beta, and LPS increase CCL1 production by LECs
      and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the
      soluble antagonist or knockdown with shRNA significantly decreased lymph node
      metastasis. Notably, inhibition of CCR8 led to the arrest of tumor cells in the
      collecting lymphatic vessels at the junction with the lymph node subcapsular
      sinus. These data identify a novel function for CCL1-CCR8 in metastasis and lymph
      node LECs as a critical checkpoint for the entry of metastases into the lymph
      nodes. 

PMID- 23878312
TI  - Remission in ankylosing spondylitis treated with anti-TNF-alpha drugs: a national
      multicentre study.
AB  - OBJECTIVE: The primary objective of this retrospective study was to investigate
      the possibility of achieving partial remission (PR) in AS patients treated with
      anti-TNF-alpha antagonists, such as adalimumab (ADA), etanercept (ETA) and
      infliximab (INF), in a real clinical practice setting. Predictors of PR were also
      evaluated. METHODS: A retrospective study was conducted in patients with AS
      treated with ADA, ETA and INF from 2000 to 2012. Kaplan-Meier survival curves
      were plotted to determine the rates of PR during the treatment with anti-TNF
      alpha drugs. RESULTS: A total of 283 patients with AS were treated with ADA
      (18.7%), ETA (26.8%) and INF (54.4%) as first anti-TNF-alpha drugs, with a PR
      rate of 57.6%. The probability of obtaining PR with ADA, ETA or INF was not
      significantly different among all anti-TNF-alpha patients. AS patients treated
      with a second anti-TNF-alpha drug had a PR rate of 40.5%, but after switching for
      lack of response, the probability of obtaining PR with a second anti-TNF-alpha
      drug was significantly lower from that of the first anti-TNF-alpha drug (P =
      0.0039). The probability of obtaining PR in patients with enthesitis (P = 0.04)
      or psoriasis (P = 0.0016) or low levels of CRP (P = 0.0225) was significantly
      lower compared with that of patients without these manifestations at baseline.
      CONCLUSION: Our real-life study on PR confirmed the effectiveness of ADA, ETA or
      INF as first or second anti-TNF-alpha drugs. The presence at baseline of
      enthesitis or psoriasis or low CRP values yielded a lower probability of
      obtaining PR.

PMID- 23878313
TI  - Essential role of the p38 mitogen-activated protein kinase pathway in tissue
      factor gene expression mediated by the phosphatidylserine-dependent
      antiprothrombin antibody.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of
      phosphatidylserine-dependent antiprothrombin antibody (aPS/PT) on the expression
      of tissue factor (TF) and the signal transduction pathway in procoagulant cells.
      METHODS: Peripheral blood mononuclear cells (PBMCs) from a healthy donor, murine
      monocyte RAW264.7 cells and human umbilical vein endothelial cells (HUVECs) were
      treated with either IgG fractions obtained from APS patients who were positive
      for aPS/PT or a murine monoclonal aPS/PT antibody, 231D, in the presence of
      prothrombin. The levels of TF mRNA were measured using real-time PCR. TF
      function, as measured by procoagulant activity, was determined with a clotting
      assay. 231D binding on the surface of treated cells was determined by flow
      cytometric analysis. Screening for phosphorylation of intracellular signalling
      proteins was conducted using an array assay. Phosphorylation of p38 MAPK was
      quantitatively analysed with ELISA, and SB203580 was used as a specific inhibitor
      of p38 MAPK. Specific siRNA for p38 MAPK was used for the knockdown assay.
      RESULTS: The IgG fractions from APS patients and 231D induced TF mRNA
      overexpression and shortening of coagulation time in cells in the presence of
      prothrombin. The 231D moiety induced phosphorylation of p38 MAPK after binding to
      the cell surface of RAW264.7 cells. SB203580 or p38 siRNA significantly hampered
      TF overexpression. CONCLUSION: Expression of TF in procoagulant cells was induced
      by aPS/PT via p38MAPK phosphorylation. This phenomenon may be correlated with the
      thrombogenicity of APS.

PMID- 23878314
TI  - CCL22-producing CD8alpha- myeloid dendritic cells mediate regulatory T cell
      recruitment in response to G-CSF treatment.
AB  - G-CSF prevents type 1 diabetes in the NOD mouse by promoting the local
      recruitment of T regulatory cells (Tregs). This is an indirect effect because
      adoptive transfer of G-CSF-induced tolerogenic dendritic cells (DCs) promotes
      Treg accumulation. However, the identity of the particular DC subset and the
      molecule(s) mediating this effect remain unknown. We demonstrate in this study
      that the adoptive transfer of CD11c(high)CD8alpha(-) DCs isolated from pegylated
      G-CSF (pegG-CSF) recipients, but not that of other DC subtypes, enhanced the
      pancreatic recruitment of CD4(+)CD25(+)Foxp3(+) Tregs, which generated increased
      amounts of TGF-beta. Likewise, only CD11c(high)CD8alpha(-) DCs from pegG-CSF
      recipients secreted the chemokine CCL22 at levels that effectively attracted
      Tregs. PegG-CSF was more efficient at enhancing the synthesis of CCL22 by
      CD11c(high)CD8alpha(-) DCs from the pancreatic lymph nodes compared with those
      from the spleen. Accordingly, CD11c(high)CD8alpha(-) DCs from the pancreatic
      lymph nodes of pegG-CSF recipients were more efficient than their splenic
      counterparts in the recruitment of Tregs upon adoptive transfer. Predictably,
      CD11c(high)CD8alpha(-) DCs failed to recruit these Tregs both in vivo and in
      vitro following intracellular neutralization of CCL22. These data assign a key
      role to CD8alpha(-) DCs and CCL22 in Treg recruitment in the protection of NOD
      mice against type 1 diabetes following the treatment with G-CSF. 

PMID- 23878315
TI  - Protein kinase C inhibitor generates stable human tolerogenic dendritic cells.
AB  - Tolerogenic dendritic cells (DCs) are a promising tool for a specific form of
      cellular therapy whereby immunological tolerance can be induced in the context of
      transplantation and autoimmunity. From libraries of bioactive lipids, nuclear
      receptor ligands, and kinase inhibitors, we screened conventional protein kinase
      C inhibitors (PKCIs) bisindolylmaleimide I, Go6983, and Ro32-0432 with strong
      tolerogenic potential. PKCI-treated human DCs were generated by subjecting them
      to a maturation process after differentiation of immature DCs. The PKCI-treated
      DCs had a semimature phenotype, showing high production of IL-10, and efficiently
      induced IL-10-producing T cells and functional Foxp3(+) regulatory T cells from
      naive CD4(+) T cells, thus eliciting a strong immunosuppressive function. They
      also showed CCR7 expression and sufficient capacity for migration toward CCR7
      ligands. Additionally, PKCI-treated DCs were highly stable when exposed to
      inflammatory stimuli such as proinflammatory cytokines or LPS. Conventional PKCIs
      inhibited NF-kappaB activation of both the canonical and noncanonical pathways of
      DC maturation, thus suppressing the expression of costimulatory molecules and IL
      12 production. High production of IL-10 in PKCI-treated DCs was due to not only
      an increase of intracellular cAMP, but also a synergistic effect of increased
      cAMP and NF-kappaB inhibition. Moreover, PKCI-treated mouse DCs that had
      properties similar to PKCI-treated human DCs prevented graft-versus-host disease
      in a murine model of acute graft-versus-host disease. Conventional PKCI-treated
      DCs may be useful for tolerance-inducing therapy, as they satisfy the required
      functional characteristics for clinical-grade tolerogenic DCs. 

PMID- 23878316
TI  - Complement activation associated with ADAMTS13 deficiency in human and murine
      thrombotic microangiopathy.
AB  - This study addressed the contribution of ADAMTS13 deficiency to complement
      activation in thrombotic thrombocytopenic purpura (TTP). Renal tissue and blood
      samples were available from 12 TTP patients. C3 and C5b-9 deposition were
      demonstrated in the renal cortex of two TTP patients, by immunofluorescence and
      immunohistochemistry, respectively. C3 was also demonstrated in the glomeruli of
      Shiga toxin-2-treated Adamts13(-/-) mice (n = 6 of 7), but less in mice that were
      not Shiga toxin-2 treated (n = 1 of 8, p < 0.05) or wild-type mice (n = 0 of 7).
      TTP patient plasma (n = 9) contained significantly higher levels of complement
      coated endothelial microparticles than control plasma (n = 13), as detected by
      flow cytometry. Exposure of histamine-stimulated primary glomerular endothelial
      cells to platelet-rich plasma from patients, or patient platelet-poor plasma
      combined with normal platelets, in a perfusion system, under shear, induced C3
      deposition on von Willebrand factor-platelet strings (on both von Willebrand
      factor and platelets) and on endothelial cells. Complement activation occurred
      via the alternative pathway. No C3 was detected when cells were exposed to TTP
      plasma that was preincubated with EDTA or heat-inactivated, or to control plasma.
      In the perfusion system, patient plasma induced more release of C3- and C9-coated
      endothelial microparticles compared with control plasma. The results indicate
      that the microvascular process induced by ADAMTS13 deficiency triggers complement
      activation on platelets and the endothelium, which may contribute to formation of
      thrombotic microangiopathy. 

PMID- 23878317
TI  - Broadening the repertoire of functional herpes simplex virus type 1-specific CD8+
      T cells reduces viral reactivation from latency in sensory ganglia.
AB  - A large proportion of the world population harbors HSV type 1 (HSV-1) in a latent
      state in their trigeminal ganglia (TG). TG-resident CD8(+) T cells appear
      important for preventing HSV-1 reactivation from latency and recurrent herpetic
      disease. In C57BL/6J mice, half of these cells are specific for an immunodominant
      epitope on HSV-1 glycoprotein B, whereas the other half are specific for 18
      subdominant epitopes. In this study, we show that the CD8(+) T cell dominance
      hierarchy in the TG established during acute infection is maintained during
      latency. However, CD8(+) T cells specific for subdominant epitopes lose
      functionality, whereas those specific for the immunodominant epitope exhibit
      increased functionality in latently infected TG. Furthermore, we show that IL-10
      produced by 16.4 +/- 2.8% of TG-resident CD4(+) T cells maintains the
      immunodominance hierarchy in part through selective inhibition of subdominant
      CD8(+) T cell proliferation. Upon systemic anti-IL-10R Ab treatment, we observed
      a significant expansion of functional subdominant CD8(+) T cells, resulting in
      significantly improved protection from viral reactivation. In fact, systemic anti
      IL-10R Ab treatment prevented viral reactivation in up to 50% of treated mice.
      Our results not only demonstrate that HSV-1 reactivation from latency can be
      prevented by expanding the repertoire of functional TG-resident CD8(+) T cells,
      but also that IL-10R blockade might have therapeutic potential to reduce or
      eliminate recurrent herpetic disease. 

PMID- 23878318
TI  - Allergens as immunomodulatory proteins: the cat dander protein Fel d 1 enhances
      TLR activation by lipid ligands.
AB  - Allergic responses can be triggered by structurally diverse allergens. Most
      allergens are proteins, yet extensive research has not revealed how they initiate
      the allergic response and why the myriad of other inhaled proteins do not. Among
      these allergens, the cat secretoglobulin protein Fel d 1 is a major allergen and
      is responsible for severe allergic responses. In this study, we show that similar
      to the mite dust allergen Der p 2, Fel d 1 substantially enhances signaling
      through the innate receptors TLR4 and TLR2. In contrast to Der p 2, however, Fel
      d 1 does not act by mimicking the TLR4 coreceptor MD2 and is not able to bind
      stably to the TLR4/MD2 complex in vitro. Fel d 1 does, however, bind to the TLR4
      agonist LPS, suggesting that a lipid transfer mechanism may be involved in the
      Fel d 1 enhancement of TLR signaling. We also show that the dog allergen Can f 6,
      a member of a distinct class of lipocalin allergens, has very similar properties
      to Fel d 1. We propose that Fel d 1 and Can f 6 belong to a group of allergen
      immunomodulatory proteins that enhance innate immune signaling and promote airway
      hypersensitivity reactions in diseases such as asthma. 

PMID- 23878320
TI  - Adipose tissue and immune function: a review of evidence relevant to HIV
      infection.
AB  - Human immunodeficiency virus type 1 (HIV) infection and antiretroviral therapy
      (ART) have long been associated with abnormalities in adipose tissue distribution
      and metabolism. More-recent evidence demonstrates that adipocytes and adipose
      resident immune cells have a role in the response to HIV. Clinical and laboratory
      studies indicate that viral proteins and antiretroviral medications alter
      adipocyte biology to enhance the persistent, systemic inflammatory state
      characteristic of untreated and treated HIV infection. Relationships between body
      composition and lymphocyte populations, cellular immune activation, and immune
      reconstitution in HIV-infected individuals receiving ART suggest that adipose
      tissue may also affect cellular immune function. This is further supported by in
      vitro studies demonstrating the effect of adipocytes and adipokines on lymphocyte
      proliferation, differentiation, and activation. Synthesis of the literature on
      adipose tissue biology and immune function in uninfected individuals may shed
      light on major outstanding research questions in the HIV field. 

PMID- 23878322
TI  - Correlating cell line studies with tissue distribution of DPP4/TMPRSS2 and human
      biological samples may better define the viral tropism of MERS-CoV.

PMID- 23878319
TI  - Vaccine-induced gag-specific T cells are associated with reduced viremia after
      HIV-1 infection.
AB  - The contribution of host T-cell immunity and HLA class I alleles to the control
      of human immunodeficiency virus (HIV-1) replication in natural infection is
      widely recognized. We assessed whether vaccine-induced T-cell immunity, or
      expression of certain HLA alleles, impacted HIV-1 control after infection in the
      Step MRKAd5/HIV-1 gag/pol/nef study. Vaccine-induced T cells were associated with
      reduced plasma viremia, with subjects targeting >=3 gag peptides presenting with
      half-log lower mean viral loads than subjects without Gag responses. This effect
      was stronger in participants infected proximal to vaccination and was independent
      of our observed association of HLA-B*27, -B*57 and -B*58:01 alleles with lower
      HIV-1 viremia. These findings support the ability of vaccine-induced T-cell
      responses to influence postinfection outcome and provide a rationale for the
      generation of T-cell responses by vaccination to reduce viremia if protection
      from acquisition is not achieved. Clinical trials identifier: NCT00095576. 

PMID- 23878321
TI  - Toxoplasma serotype is associated with development of ocular toxoplasmosis.
AB  - BACKGROUND: Worldwide, ocular toxoplasmosis (OT) is the principal cause of
      posterior uveitis, a severe, life-altering disease. A Toxoplasma gondii enzyme
      linked immunoassay that detects strain-specific antibodies present in serum was
      used to correlate serotype with disease. METHODS: Toxoplasma serotypes in
      consecutive serum samples from German uveitis patients with OT were compared with
      non-OT seropositive patients with noninfectious autoimmune posterior uveitis. OT
      patients were tested for association of parasite serotype with age, gender,
      location, clinical onset, size, visual acuity, or number of lesions (mean follow
      up, 3.8 years) to determine association with recurrences. RESULTS: A novel,
      nonreactive (NR) serotype was detected more frequently in serum samples of OT
      patients (50/114, 44%) than in non-OT patients (4/56, 7%) (odds ratio, 10.0; 95%
      confidence interval 3.4-40.8; P < .0001). Non-OT patients were predominantly
      infected with Type II strains (39/56; 70%), consistent with expected frequencies
      in Central Europe. Among OT patients, those with NR serotypes experienced more
      frequent recurrences (P = .037). Polymerase chain reaction detected parasite DNA
      in 8/60 OT aqueous humor specimens but failed to identify Type II strain alleles.
      CONCLUSIONS: Toxoplasma NR and Type II serotypes predominate in German OT
      patients. The NR serotype is associated with OT recurrences, underscoring the
      value of screening for management of disease.

PMID- 23878323
TI  - Reply to Leow.

PMID- 23878324
TI  - A novel calcium-dependent protein kinase inhibitor as a lead compound for
      treating cryptosporidiosis.
AB  - Cryptosporidium parasites infect intestinal cells, causing cryptosporidiosis.
      Despite its high morbidity and association with stunting in the developing world,
      current therapies for cryptosporidiosis have limited efficacy. Calcium-dependent
      protein kinases (CDPKs) are essential enzymes in the biology of protozoan
      parasites. CDPK1 was cloned from the genome of Cryptosporidium parvum, and potent
      and specific inhibitors have been developed based on structural studies. In this
      study, we evaluated the anti-Cryptosporidium activity of a novel CDPK1 inhibitor,
      1294, and demonstrated that 1294 significantly reduces parasite infection in
      vitro, with a half maximal effective concentration of 100 nM. Pharmacokinetic
      studies revealed that 1294 is well absorbed, with a half-life supporting daily
      administration. Oral therapy with 1294 eliminated Cryptosporidium parasites from
      6 of 7 infected severe combined immunodeficiency-beige mice, and the parasites
      did not recur in these immunosuppressed mice. Mice treated with 1294 had less
      epithelial damage, corresponding to less apoptosis. Thus, 1294 is an important
      lead for the development of drugs for treatment of cryptosporidiosis. 

PMID- 23878325
TI  - The nasal mucosa contains a large spectrum of human papillomavirus types from the
      Betapapillomavirus and Gammapapillomavirus genera.
AB  - BACKGROUND:  Human papillomavirus (HPV) types from the Betapapillomavirus and
      Gammapapillomavirus genera are common at cutaneous sites. The aim of this study
      was to analyze the prevalence of these HPV types in oral and nasal samples.
      METHODS:  Nasal samples and oral samples were obtained from 312 volunteer Danish
      healthcare staff (240 women and 72 men), among whom the mean age was 42 years. A
      total of 311 oral samples and 304 nasal samples were eligible for HPV DNA
      analysis. HPV types were detected by use of polymerase chain reactions with
      modified general primers (MGP) and Forslund-Antonsson primers (FAP) and
      identified by Luminex (for types detected by MGP PCR) or direct sequencing or
      cloning before sequencing (for types detected by FAP PCR). RESULTS:  HPV DNA was
      detected in 6% of the oral samples and 50% of the nasal samples. Seventy-five
      diverse HPV types or putative HPV types were identified. HPV types within the
      Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus genera were
      detected in 3%, 31%, and 23% of the nasal samples, respectively. A putative
      subtype of HPV76, originally isolated from a feline oral squamous cell carcinoma,
      was detected in 7 nasal samples. CONCLUSION:  A large spectrum of HPV types from
      Betapapillomavirus and Gammapapillomavirus have tropism for the nasal mucosa. The
      implication of the relatively high prevalence of these viruses in the nasal
      mucosa is unknown.

PMID- 23878326
TI  - The past, present and future of Africa's rainforests.

PMID- 23878328
TI  - Congo Basin rainfall climatology: can we believe the climate models?
AB  - The Congo Basin is one of three key convective regions on the planet which,
      during the transition seasons, dominates global tropical rainfall. There is
      little agreement as to the distribution and quantity of rainfall across the basin
      with datasets differing by an order of magnitude in some seasons. The location of
      maximum rainfall is in the far eastern sector of the basin in some datasets but
      the far western edge of the basin in others during March to May. There is no
      consistent pattern to this rainfall distribution in satellite or model datasets.
      Resolving these differences is difficult without ground-based data. Moisture flux
      nevertheless emerges as a useful variable with which to study these differences.
      Climate models with weak (strong) or even divergent moisture flux over the basin
      are dry (wet). The paper suggests an approach, via a targeted field campaign, for
      generating useful climate information with which to confront rainfall products
      and climate models. 

PMID- 23878329
TI  - Implications of global warming for the climate of African rainforests.
AB  - African rainforests are likely to be vulnerable to changes in temperature and
      precipitation, yet there has been relatively little research to suggest how the
      regional climate might respond to global warming. This study presents projections
      of temperature and precipitation indices of relevance to African rainforests,
      using global climate model experiments to identify local change as a function of
      global temperature increase. A multi-model ensemble and two perturbed physics
      ensembles are used, one with over 100 members. In the east of the Congo Basin,
      most models (92%) show a wet signal, whereas in west equatorial Africa, the
      majority (73%) project an increase in dry season water deficits. This drying is
      amplified as global temperature increases, and in over half of coupled models by
      greater than 3% per  degrees C of global warming. Analysis of atmospheric
      dynamics in a subset of models suggests that this could be partly because of a
      rearrangement of zonal circulation, with enhanced convection in the Indian Ocean
      and anomalous subsidence over west equatorial Africa, the Atlantic Ocean and, in
      some seasons, the Amazon Basin. Further research to assess the plausibility of
      this and other mechanisms is important, given the potential implications of
      drying in these rainforest regions. 

PMID- 23878327
TI  - Above-ground biomass and structure of 260 African tropical forests.
AB  - We report above-ground biomass (AGB), basal area, stem density and wood mass
      density estimates from 260 sample plots (mean size: 1.2 ha) in intact closed
      canopy tropical forests across 12 African countries. Mean AGB is 395.7 Mg dry
      mass ha-1 (95% CI: 14.3), substantially higher than Amazonian values, with the
      Congo Basin and contiguous forest region attaining AGB values (429 Mg ha-1)
      similar to those of Bornean forests, and significantly greater than East or West
      African forests. AGB therefore appears generally higher in palaeo- compared with
      neotropical forests. However, mean stem density is low (426 +/- 11 stems ha-1
      greater than or equal to 100 mm diameter) compared with both Amazonian and
      Bornean forests (cf. approx. 600) and is the signature structural feature of
      African tropical forests. While spatial autocorrelation complicates analyses, AGB
      shows a positive relationship with rainfall in the driest nine months of the
      year, and an opposite association with the wettest three months of the year; a
      negative relationship with temperature; positive relationship with clay-rich
      soils; and negative relationships with C : N ratio (suggesting a positive soil
      phosphorus-AGB relationship), and soil fertility computed as the sum of base
      cations. The results indicate that AGB is mediated by both climate and soils, and
      suggest that the AGB of African closed-canopy tropical forests may be
      particularly sensitive to future precipitation and temperature changes.

PMID- 23878330
TI  - Attribution of changes in precipitation patterns in African rainforests.
AB  - Tropical rainforests in Africa are one of the most under-researched regions in
      the world, but research in the Amazonian rainforest suggests potential
      vulnerability to climate change. Using the large ensemble of Atmosphere-only
      general circulation model (AGCM) simulations within the weather@home project,
      statistics of precipitation in the dry season of the Congo Basin rainforest are
      analysed. By validating the model simulation against observations, we could
      identify a good model performance for the June, July, August (JJA) dry season,
      but this result does need to be taken with caution as observed data are of poor
      quality. Additional validation methods have been used to investigate the
      applicability of probabilistic event attribution analysis from large model
      ensembles to a tropical region, in this case the Congo Basin. These methods
      corroborate the confidence in the model, leading us to believe the attribution
      result to be robust. That is, that there are no significant changes in the risk
      of low precipitation extremes during this dry season (JJA) precipitation in the
      Congo Basin. Results for the December, January, February dry season are less
      clear. The study highlights that attribution analysis has the potential to
      provide valuable scientific evidence of recent or anticipated climatological
      changes, especially in regions with sparse observational data and unclear
      projections of future changes. However, the strong influence of sea surface
      temperature teleconnection patterns on tropical precipitation provides more
      challenges in the set up of attribution studies than midlatitude rainfall. 

PMID- 23878331
TI  - State and evolution of the African rainforests between 1990 and 2010.
AB  - This paper presents a map of Africa's rainforests for 2005. Derived from moderate
      resolution imaging spectroradiometer data at a spatial resolution of 250 m and
      with an overall accuracy of 84%, this map provides new levels of spatial and
      thematic detail. The map is accompanied by measurements of deforestation between
      1990, 2000 and 2010 for West Africa, Central Africa and Madagascar derived from a
      systematic sample of Landsat images-imagery from equivalent platforms is used to
      fill gaps in the Landsat record. Net deforestation is estimated at 0.28% yr(-1)
      for the period 1990-2000 and 0.14% yr(-1) for the period 2000-2010. West Africa
      and Madagascar exhibit a much higher deforestation rate than the Congo Basin, for
      example, three times higher for West Africa and nine times higher for Madagascar.
      Analysis of variance over the Congo Basin is then used to show that expanding
      agriculture and increasing fuelwood demands are key drivers of deforestation in
      the region, whereas well-controlled timber exploitation programmes have little or
      no direct influence on forest-cover reduction at present. Rural and urban
      population concentrations and fluxes are also identified as strong underlying
      causes of deforestation in this study. 

PMID- 23878332
TI  - Tropical forest recovery from logging: a 24 year silvicultural experiment from
      Central Africa.
AB  - Large areas of African moist forests are being logged in the context of
      supposedly sustainable management plans. It remains however controversial whether
      harvesting a few trees per hectare can be maintained in the long term while
      preserving other forest services as well. We used a unique 24 year silvicultural
      experiment, encompassing 10 4 ha plots established in the Central African
      Republic, to assess the effect of disturbance linked to logging (two to nine
      trees ha-1 greater than or equal to 80 cm DBH) and thinning (11-41 trees ha-1
      greater than or equal to 50 cm DBH) on the structure and dynamics of the forest.
      Before silvicultural treatments, above-ground biomass (AGB) and timber stock
      (i.e. the volume of commercial trees greater than or equal to 80 cm DBH) in the
      plots amounted 374.5 +/- 58.2 Mg ha-1 and 79.7 +/- 45.9 m3 ha-1, respectively. We
      found that (i) natural control forest was increasing in AGB (2.58 +/- 1.73 Mg dry
      mass ha-1 yr-1) and decreasing in timber stock (-0.33 +/- 1.57 m3 ha-1 yr-1);
      (ii) the AGB recovered very quickly after logging and thinning, at a rate
      proportional to the disturbance intensity (mean recovery after 24 years: 144%).
      Compared with controls, the gain almost doubled in the logged plots (4.82 +/-
      1.22 Mg ha-1 yr-1) and tripled in the logged + thinned plots (8.03 +/- 1.41 Mg ha
      1 yr-1); (iii) the timber stock recovered slowly (mean recovery after 24 years:
      41%), at a rate of 0.75 +/- 0.51 m3 ha-1 yr-1 in the logged plots, and 0.81 +/-
      0.74 m3 ha-1 yr-1 in the logged + thinned plots. Although thinning significantly
      increased the gain in biomass, it had no effect on the gain in timber stock.
      However, thinning did foster the growth and survival of small- and medium-sized
      timber trees and should have a positive effect over the next felling cycle.

PMID- 23878333
TI  - Extent and ecological consequences of hunting in Central African rainforests in
      the twenty-first century.
AB  - Humans have hunted wildlife in Central Africa for millennia. Today, however, many
      species are being rapidly extirpated and sanctuaries for wildlife are dwindling.
      Almost all Central Africa's forests are now accessible to hunters. Drastic
      declines of large mammals have been caused in the past 20 years by the commercial
      trade for meat or ivory. We review a growing body of empirical data which shows
      that trophic webs are significantly disrupted in the region, with knock-on
      effects for other ecological functions, including seed dispersal and forest
      regeneration. Plausible scenarios for land-use change indicate that increasing
      extraction pressure on Central African forests is likely to usher in new worker
      populations and to intensify the hunting impacts and trophic cascade disruption
      already in progress, unless serious efforts are made for hunting regulation. The
      profound ecological changes initiated by hunting will not mitigate and may even
      exacerbate the predicted effects of climate change for the region. We hypothesize
      that, in the near future, the trophic changes brought about by hunting will have
      a larger and more rapid impact on Central African rainforest structure and
      function than the direct impacts of climate change on the vegetation. Immediate
      hunting regulation is vital for the survival of the Central African rainforest
      ecosystem. 

PMID- 23878334
TI  - Climatic and cultural changes in the west Congo Basin forests over the past 5000
      years.
AB  - Central Africa includes the world's second largest rainforest block. The ecology
      of the region remains poorly understood, as does its vegetation and
      archaeological history. However, over the past 20 years, multidisciplinary
      scientific programmes have enhanced knowledge of old human presence and
      palaeoenvironments in the forestry block of Central Africa. This first regional
      synthesis documents significant cultural changes over the past five millennia and
      describes how they are linked to climate. It is now well documented that climatic
      conditions in the African tropics underwent significant changes throughout this
      period and here we demonstrate that corresponding shifts in human demography have
      had a strong influence on the forests. The most influential event was the decline
      of the strong African monsoon in the Late Holocene, resulting in serious
      disturbance of the forest block around 3500 BP. During the same period,
      populations from the north settled in the forest zone; they mastered new
      technologies such as pottery and fabrication of polished stone tools, and seem to
      have practised agriculture. The opening up of forests from 2500 BP favoured the
      arrival of metallurgist populations that impacted the forest. During this long
      period (2500-1400 BP), a remarkable increase of archaeological sites is an
      indication of a demographic explosion of metallurgist populations. Paradoxically,
      we have found evidence of pearl millet (Pennisetum glaucum) cultivation in the
      forest around 2200 BP, implying a more arid context. While Early Iron Age sites
      (prior to 1400 BP) and recent pre-colonial sites (two to eight centuries BP) are
      abundant, the period between 1600 and 1000 BP is characterized by a sharp
      decrease in human settlements, with a population crash between 1300 and 1000 BP
      over a large part of Central Africa. It is only in the eleventh century that new
      populations of metallurgists settled into the forest block. In this paper, we
      analyse the spatial and temporal distribution of 328 archaeological sites that
      have been reliably radiocarbon dated. The results allow us to piece together
      changes in the relationships between human populations and the environments in
      which they lived. On this basis, we discuss interactions between humans, climate
      and vegetation during the past five millennia and the implications of the absence
      of people from the landscape over three centuries. We go on to discuss modern
      vegetation patterns and African forest conservation in the light of these events.

PMID- 23878335
TI  - Response of African humid tropical forests to recent rainfall anomalies.
AB  - During the last decade, strong negative rainfall anomalies resulting from
      increased sea surface temperature in the tropical Atlantic have caused extensive
      droughts in rainforests of western Amazonia, exerting persistent effects on the
      forest canopy. In contrast, there have been no significant impacts on rainforests
      of West and Central Africa during the same period, despite large-scale droughts
      and rainfall anomalies during the same period. Using a combination of rainfall
      observations from meteorological stations from the Climate Research Unit (CRU;
      1950-2009) and satellite observations of the Tropical Rainfall Measuring Mission
      (TRMM; 1998-2010), we show that West and Central Africa experienced strong
      negative water deficit (WD) anomalies over the last decade, particularly in 2005,
      2006 and 2007. These anomalies were a continuation of an increasing drying trend
      in the region that started in the 1970s. We monitored the response of forests to
      extreme rainfall anomalies of the past decade by analysing the microwave
      scatterometer data from QuickSCAT (1999-2009) sensitive to variations in canopy
      water content and structure. Unlike in Amazonia, we found no significant impacts
      of extreme WD events on forests of Central Africa, suggesting potential
      adaptability of these forests to short-term severe droughts. Only forests near
      the savanna boundary in West Africa and in fragmented landscapes of the northern
      Congo Basin responded to extreme droughts with widespread canopy disturbance that
      lasted only during the period of WD. Time-series analyses of CRU and TRMM data
      show most regions in Central and West Africa experience seasonal or decadal
      extreme WDs (less than -600 mm). We hypothesize that the long-term historical
      extreme WDs with gradual drying trends in the 1970s have increased the
      adaptability of humid tropical forests in Africa to droughts. 

PMID- 23878336
TI  - Vegetation structure and greenness in Central Africa from Modis multi-temporal
      data.
AB  - African forests within the Congo Basin are generally mapped at a regional scale
      as broad-leaved evergreen forests, with the main distinction being between terra
      firme and swamp forest types. At the same time, commercial forest inventories, as
      well as national maps, have highlighted a strong spatial heterogeneity of forest
      types. A detailed vegetation map generated using consistent methods is needed to
      inform decision makers about spatial forest organization and their relationships
      with environmental drivers in the context of global change. We propose a multi
      temporal remotely sensed data approach to characterize vegetation types using
      vegetation index annual profiles. The classifications identified 22 vegetation
      types (six savannas, two swamp forests, 14 forest types) improving existing
      vegetation maps. Among forest types, we showed strong variations in stand
      structure and deciduousness, identifying (i) two blocks of dense evergreen
      forests located in the western part of the study area and in the central part on
      sandy soils; (ii) semi-deciduous forests are located in the Sangha River interval
      which has experienced past fragmentation and human activities. For all vegetation
      types enhanced vegetation index profiles were highly seasonal and strongly
      correlated to rainfall and to a lesser extent, to light regimes. These results
      are of importance to predict spatial variations of carbon stocks and fluxes,
      because evergreen/deciduous forests (i) have contrasted annual dynamics of
      photosynthetic activity and foliar water content and (ii) differ in community
      dynamics and ecosystem processes. 

PMID- 23878337
TI  - Financing and current capacity for REDD+ readiness and monitoring, measurement,
      reporting and verification in the Congo Basin.
AB  - This paper provides the first critical analysis of the financing and current
      capacity for REDD+ readiness in the Congo Basin, with a particular focus on the
      REDD+ component of national forest monitoring and measurement, reporting and
      verification (M&MRV). We focus on three areas of analysis: (i) general financing
      for REDD+ readiness especially M&MRV; (ii) capacity and information for REDD+
      implementation and M&MRV; (iii) prospects and challenges for REDD+ and M&MRV
      readiness in terms of financing and capacity. For the first area of analysis, a
      REDD+ and M&MRV readiness financing database was created based on the information
      from the REDD+ voluntary database and Internet searches. For the second area of
      analysis, a qualitative approach to data collection was adopted (semi-structured
      interviews with key stakeholders, surveys and observations). All 10 countries
      were visited between 2010 and 2012. We find that: (i) a significant amount of
      REDD+ financing flows into the Congo Basin (+/-US$550 million or almost half of
      the REDD+ financing for the African continent); (ii) across countries, there is
      an important disequilibrium in terms of REDD+ and M&MRV readiness financing,
      political engagement, comprehension and capacity, which also appears to be a key
      barrier to countries receiving equal resources; (iii) most financing appears to
      go to smaller scale (subnational) REDD+ projects; (iv) four distinct country
      groups in terms of REDD+ readiness and M&MRV status are identified; and (v) the
      Congo Basin has a distinct opportunity to have a specific REDD+ financing window
      for large-scale and more targeted national REDD+ programmes through a specific
      fund for the region. 

PMID- 23878338
TI  - The community resource management area mechanism: a strategy to manage African
      forest resources for REDD+.
AB  - Climate change poses a significant threat to Africa, and deforestation rates have
      increased in recent years. Mitigation initiatives such as REDD+ are widely
      considered as potentially efficient ways to generate emission reductions (or
      removals), conserve or sustainably manage forests, and bring benefits to
      communities, but effective implementation models are lacking. This paper presents
      the case of Ghana's Community Resource Management Area (CREMA) mechanism, an
      innovative natural resource governance and landscape-level planning tool that
      authorizes communities to manage their natural resources for economic and
      livelihood benefits. This paper argues that while the CREMA was originally
      developed to facilitate community-based wildlife management and habitat
      protection, it offers a promising community-based structure and process for
      managing African forest resources for REDD+. At a theoretical level, it conforms
      to the ecological, socio-cultural and economic factors that drive resource-users'
      decision process and practices. And from a practical mitigation standpoint, the
      CREMA has the potential to help solve many of the key challenges for REDD+ in
      Africa, including definition of boundaries, smallholder aggregation, free prior
      and informed consent, ensuring permanence, preventing leakage, clarifying land
      tenure and carbon rights, as well as enabling equitable benefit-sharing
      arrangements. Ultimately, CREMA's potential as a forest management and climate
      change mitigation strategy that generates livelihood benefits for smallholder
      farmers and forest users will depend upon the willingness of African governments
      to support the mechanism and give it full legislative backing, and the motivation
      of communities to adopt the CREMA and integrate democratic decision-making and
      planning with their traditional values and natural resource management systems. 

PMID- 23878339
TI  - African rainforests: past, present and future.
AB  - The rainforests are the great green heart of Africa, and present a unique
      combination of ecological, climatic and human interactions. In this synthesis
      paper, we review the past and present state processes of change in African
      rainforests, and explore the challenges and opportunities for maintaining a
      viable future for these biomes. We draw in particular on the insights and new
      analyses emerging from the Theme Issue on 'African rainforests: past, present and
      future' of Philosophical Transactions of the Royal Society B. A combination of
      features characterize the African rainforest biome, including a history of
      climate variation; forest expansion and retreat; a long history of human
      interaction with the biome; a relatively low plant species diversity but large
      tree biomass; a historically exceptionally high animal biomass that is now being
      severely hunted down; the dominance of selective logging; small-scale farming and
      bushmeat hunting as the major forms of direct human pressure; and, in Central
      Africa, the particular context of mineral- and oil-driven economies that have
      resulted in unusually low rates of deforestation and agricultural activity. We
      conclude by discussing how this combination of factors influences the prospects
      for African forests in the twenty-first century. 

PMID- 23878340
TI  - African tropical rainforest net carbon dioxide fluxes in the twentieth century.
AB  - The African humid tropical biome constitutes the second largest rainforest
      region, significantly impacts global carbon cycling and climate, and has
      undergone major changes in functioning owing to climate and land-use change over
      the past century. We assess changes and trends in CO2 fluxes from 1901 to 2010
      using nine land surface models forced with common driving data, and depict the
      inter-model variability as the uncertainty in fluxes. The biome is estimated to
      be a natural (no disturbance) net carbon sink (-0.02 kg C m-2 yr-1 or -0.04 Pg C
      yr-1, p < 0.05) with increasing strength fourfold in the second half of the
      century. The models were in close agreement on net CO2 flux at the beginning of
      the century (sigma1901 = 0.02 kg C m-2 yr-1), but diverged exponentially
      throughout the century (sigma2010 = 0.03 kg C m-2 yr-1). The increasing
      uncertainty is due to differences in sensitivity to increasing atmospheric CO2,
      but not increasing water stress, despite a decrease in precipitation and increase
      in air temperature. However, the largest uncertainties were associated with the
      most extreme drought events of the century. These results highlight the need to
      constrain modelled CO2 fluxes with increasing atmospheric CO2 concentrations and
      extreme climatic events, as the uncertainties will only amplify in the next
      century.

PMID- 23878341
TI  - The national determinants of deforestation in sub-Saharan Africa.
AB  - For decades, the dynamics of tropical deforestation in sub-Saharan Africa (SSA)
      have defied easy explanation. The rates of deforestation have been lower than
      elsewhere in the tropics, and the driving forces evident in other places,
      government new land settlement schemes and industrialized agriculture, have
      largely been absent in SSA. The context and causes for African deforestation
      become clearer through an analysis of new, national-level data on forest cover
      change for SSA countries for the 2000-2005 period. The recent dynamic in SSA
      varies from dry to wet biomes. Deforestation occurred at faster rates in nations
      with predominantly dry forests. The wetter Congo basin countries had lower rates
      of deforestation, in part because tax receipts from oil and mineral industries in
      this region spurred rural to urban migration, declines in agriculture and
      increased imports of cereals from abroad. In this respect, the Congo basin
      countries may be experiencing an oil and mineral fuelled forest transition. Small
      farmers play a more important role in African deforestation than they do in
      southeast Asia and Latin America, in part because small-scale agriculture remains
      one of the few livelihoods open to rural peoples. 

PMID- 23878342
TI  - Woody encroachment and forest degradation in sub-Saharan Africa's woodlands and
      savannas 1982-2006.
AB  - We review the literature and find 16 studies from across Africa's savannas and
      woodlands where woody encroachment dominates. These small-scale studies are
      supplemented by an analysis of long-term continent-wide satellite data,
      specifically the Normalized Difference Vegetation Index (NDVI) time series from
      the Global Inventory Modeling and Mapping Studies (GIMMS) dataset. Using dry
      season data to separate the tree and grass signals, we find 4.0% of non
      rainforest woody vegetation in sub-Saharan Africa (excluding West Africa)
      significantly increased in NDVI from 1982 to 2006, whereas 3.52% decreased. The
      increases in NDVI were found predominantly to the north of the Congo Basin, with
      decreases concentrated in the Miombo woodland belt. We hypothesize that areas of
      increasing dry-season NDVI are undergoing woody encroachment, but the coarse
      resolution of the study and uncertain relationship between NDVI and woody cover
      mean that the results should be interpreted with caution; certainly, these
      results do not contradict studies finding widespread deforestation throughout the
      continent. However, woody encroachment could be widespread, and warrants further
      investigation as it has important consequences for the global carbon cycle and
      land-climate interactions. 

PMID- 23878343
TI  - Determining the response of African biota to climate change: using the past to
      model the future.
AB  - Prediction of biotic responses to future climate change in tropical Africa tends
      to be based on two modelling approaches: bioclimatic species envelope models and
      dynamic vegetation models. Another complementary but underused approach is to
      examine biotic responses to similar climatic changes in the past as evidenced in
      fossil and historical records. This paper reviews these records and highlights
      the information that they provide in terms of understanding the local- and
      regional-scale responses of African vegetation to future climate change. A key
      point that emerges is that a move to warmer and wetter conditions in the past
      resulted in a large increase in biomass and a range distribution of woody plants
      up to 400-500 km north of its present location, the so-called greening of the
      Sahara. By contrast, a transition to warmer and drier conditions resulted in a
      reduction in woody vegetation in many regions and an increase in grass/savanna
      dominated landscapes. The rapid rate of climate warming coming into the current
      interglacial resulted in a dramatic increase in community turnover, but there is
      little evidence for widespread extinctions. However, huge variation in biotic
      response in both space and time is apparent with, in some cases, totally
      different responses to the same climatic driver. This highlights the importance
      of local features such as soils, topography and also internal biotic factors in
      determining responses and resilience of the African biota to climate change,
      information that is difficult to obtain from modelling but is abundant in
      palaeoecological records. 

PMID- 23878344
TI  - Fish consumption and colorectal cancer risk: an evaluation based on a systematic
      review of epidemiologic evidence among the Japanese population.
AB  - OBJECTIVE: The association between fish consumption and colorectal cancer risk
      remains inconclusive. The present study systematically reviewed and meta-analyzed
      epidemiologic data on the association between fish consumption and colorectal
      cancer risk among Japanese. METHODS: Original data were obtained from MEDLINE
      searched using PubMed or from searches of the Ichushi database, complemented with
      manual searches. The associations were evaluated based on the strength of
      evidence, the magnitude of association and biologic plausibility. Meta-analysis
      was conducted according to the study design. RESULTS: Five cohort studies and 12
      case-control studies were identified. Fish consumption was not significantly
      associated with colorectal, colon or rectal cancer risks. One cohort study showed
      a weak positive association with colorectal cancer, and another showed a weak
      inverse association with colon cancer in men and a moderate and weak inverse
      association with colon and rectal cancers in women. As regards case-control
      studies, four studies reported a weak inverse association, whereas one showed a
      weak positive association with colon cancer. Regarding rectal cancer, four case
      control studies showed a weak inverse association, but two reported a weak-to
      moderate positive association. The pooled relative risk/odds ratio (95%
      confidence interval) of colorectal cancer for the highest versus lowest category
      of fish consumption was 1.03 (0.89-1.18) and 0.84 (0.75-0.94) for cohort and case
      control studies, respectively. CONCLUSIONS: There was insufficient evidence to
      support an association between fish consumption and the risk of colorectal cancer
      among Japanese.

PMID- 23878345
TI  - A retrospective study of 5-year outcomes of radiotherapy for gastric mucosa
      associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication
      therapy.
AB  - BACKGROUND: The favorable response rate of radiotherapy for localized gastric
      mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori
      eradication has been demonstrated. However, there are limited data available on
      the long-term outcomes. The aim of this retrospective study was to evaluate the
      long-term outcomes of radiotherapy for localized gastric mucosa-associated
      lymphoid tissue lymphoma refractory to Helicobacter pylori eradication. METHODS:
      Thirty-four consecutive patients with localized gastric mucosa-associated
      lymphoid tissue lymphoma that were refractory to eradication were treated with
      radiotherapy (a total dose of 30 Gy). The response and adverse events of
      radiotherapy were retrospectively analyzed as short-term outcomes, and recurrence
      free, overall and disease-specific survival rates were calculated as long-term
      outcomes. RESULTS: Thirty-three (97.1%) patients achieved complete remission and
      radiotherapy was well tolerated. One patient underwent emergency gastrectomy due
      to severe hematemesis. Of the 34 patients during the median follow-up period of
      7.5 (1.2-13.0) years, one patient had local recurrence after 8.8 years, one
      patient underwent surgery for bowel obstruction secondary to small bowel
      metastasis after 5.1 years and one patient had pulmonary metastasis after 10.9
      years. Pathologically, all three recurrences revealed mucosa-associated lymphoid
      tissue lymphoma without any transformation to high-grade lymphoma. None died of
      gastric mucosa-associated lymphoid tissue lymphoma. The 5-year recurrence-free
      survival rate was 97.0%. The 5-year overall survival rates and disease-specific
      survival rates were 97.0 and 100%, respectively. CONCLUSIONS: Radiotherapy in
      patients with localized gastric mucosa-associated lymphoid tissue lymphoma
      refractory to Helicobacter pylori eradication can achieve excellent overall
      survival. However, long-term surveillance is necessary to identify late
      recurrences.

PMID- 23878346
TI  - The measurement accuracy of passive radon instruments.
AB  - This paper analyses the data having been gathered from interlaboratory
      comparisons of passive radon instruments over 10 y with respect to the
      measurement accuracy. The measurement accuracy is discussed in terms of the
      systematic and the random measurement error. The analysis shows that the
      systematic measurement error of the most instruments issued by professional
      laboratory services can be within a range of +/-10 % from the true value. A
      single radon measurement has an additional random measurement error, which is in
      the range of up to +/-15 % for high exposures to radon (>2000 kBq h m(-3)). The
      random measurement error increases for lower exposures. The analysis especially
      applies to instruments with solid-state nuclear track detectors and results in
      proposing criteria for testing the measurement accuracy. Instruments with
      electrets and charcoal have also been considered, but the low stock of data
      enables only a qualitative discussion. 

PMID- 23878347
TI  - Clinical equipoise: actual or hypothetical disagreement?
AB  - In his influential 1987 essay, "Equipoise and The Ethics of Randomized Clinical
      Research," Benjamin Freedman argued that Charles Fried's theoretical equipoise
      requirement threatened clinical research because it was overwhelmingly fragile
      and rendered unethical too many randomized clinical trials. Freedman, therefore,
      proposed an alternative requirement, the clinical equipoise requirement, which is
      now considered to be the fundamental or guiding principle concerning the ethics
      of enrolling patients in randomized clinical trials. In this essay I argue that
      Freedman's clinical equipoise requirement is ambiguous and can be interpreted in
      (at least) two different ways. I furthermore claim that, ironically, the best
      interpretation of the clinical equipoise requirement opens Freedman to the same
      objection that he leveled against Fried twenty-five years ago; namely, that it
      (Freedman's clinical equipoise requirement) renders unethical too many randomized
      clinical trials. 

PMID- 23878348
TI  - Pragmatism, metaphysics, and bioethics: beyond a theory of moral deliberation.
AB  - Pragmatism has been understood by bioethicists as yet another rival in the
      "methods wars," as yet another theory of moral deliberation. This has led to
      criticism of pragmatic bioethics as both theoretically and practically
      inadequate. Pragmatists' responses to these objections have focused mainly on
      misunderstandings of pragmatism's epistemology. These responses are insufficient.
      Pragmatism's commitment to radical empiricism gives it theoretical resources
      unappreciated by critics and defenders alike. Radical empiricism, unlike its more
      traditional ancestors, undercuts the gaps between theory and practice, and
      subjective and objective accounts of experience, and in so doing provides the
      metaphysical and epistemological basis for a thoroughgoing empirical naturalism
      in ethics. Pragmatism's strength as an approach to moral problems thus emerges as
      a result of a much wider array of resources than contemporary interpreters have
      acknowledged, which makes it a richer, deeper framework for understanding moral
      deliberation in general and bioethical decision making in particular. 

PMID- 23878349
TI  - Maturity onset diabetes of the young: identification and diagnosis.
AB  - Maturity-onset diabetes of the young (MODY) is a monogenic disorder that results
      in a familial, young-onset non-insulin dependent form of diabetes, typically
      presenting in lean young adults before 25 years. Approximately 1% of diabetes has
      a monogenic cause but this is frequently misdiagnosed as Type 1 or Type 2
      diabetes. A correct genetic diagnosis is important as it often leads to improved
      treatment for those affected with diabetes and enables predictive genetic testing
      for their asymptomatic relatives. An early diagnosis together with appropriate
      treatment is essential for reducing the risk of diabetic complications in later
      life. Mutations in the GCK and HNF1A/4 A genes account for up to 80% of all MODY
      cases. Mutations in the GCK gene cause a mild, asymptomatic and non-progressive
      fasting hyperglycaemia from birth usually requiring no treatment. In contrast,
      mutations in the genes encoding the transcription factors HNF1A and HNF4A cause a
      progressive insulin secretory defect and hyperglycaemia that can lead to vascular
      complications. The diabetes in these patients is usually well controlled with
      sulphonylurea tablets although insulin treatment may be required in later life.
      In this review, we outline the key clinical and laboratory characteristics of the
      common and rarer causes of MODY with the aim of raising awareness of this
      condition amongst health-care scientists. 

PMID- 23878351
TI  - BRAF mutation and microsatellite instability status in colonic and rectal
      carcinoma: context really does matter.

PMID- 23878350
TI  - Cancer incidence trends among Asian American populations in the United States,
      1990-2008.
AB  - BACKGROUND: National cancer incidence trends are presented for eight Asian
      American groups: Asian Indians/Pakistanis, Chinese, Filipinos, Japanese,
      Kampucheans, Koreans, Laotians, and Vietnamese. METHODS: Cancer incidence data
      from 1990 through 2008 were obtained from 13 Surveillance, Epidemiology, End
      Results (SEER) registries. Incidence rates from 1990 through 2008 and average
      percentage change were computed using SEER*Stat and Joinpoint software. The
      annual percentage change (APC) in incidence rates was estimated with 95%
      confidence intervals (95% CIs) calculated for both the rate and APC estimates.
      Rates for non-Hispanic whites are presented for comparison. RESULTS: Prostate
      cancer was the most common malignancy among most groups, followed by lung,
      colorectal, liver, and stomach cancers. Breast cancer was generally the most
      common cancer in women, followed by colorectal and lung cancers; liver, cervix,
      thyroid, and stomach cancers also ranked highly. Among men, increasing trends
      were observed for prostate (Asian Indians and Pakistanis: APC 1990-2003 = 2.2,
      95% CI = 0.3 to 4.1; Filipinos: APC 1990-1994 = 19.0, 95% CI = 4.5 to 35.4;
      Koreans: APC 1990-2008 = 2.9, 95% CI = 1.8 to 4.0), colorectal (Koreans: APC 1990
      2008 = 2.2, 95% CI = 0.9 to 3.5), and liver cancers (Filipinos: APC 1990-2008 =
      1.6, 95% CI = 0.4 to 2.7; Koreans: APC 1990-2006 = 2.1, 95% CI = 0.4 to 3.7;
      Vietnamese: APC 1990-2008 = 1.6, 95% CI = 0.3 to 2.8), whereas lung and stomach
      cancers generally remained stable or decreased. Among women, increases were
      observed for uterine cancer (Asian Indians: APC 1990-2008 = 3.0, 95% CI = 0.3 to
      5.8; Chinese: APC 2004-2008 = 7.0, 95% CI = 1.4 to 12.9; Filipina: APC 1990-2008
      = 3.0, 95% CI = 2.4 to 3.7; Japanese: APC 1990-2008 = 1.1, 95% CI = 0.1 to 2.0),
      colorectal cancer (Koreans: APC 1990-2008 = 2.8, 95% CI = 1.7 to 3.9; Laotians:
      APC: 1990-2008 = 5.9, 95% CI = 4.0 to 7.7), lung cancer (Filipinas: APC 1990-2008
      = 2.1, 95% CI = 1.4 to 2.8; Koreans: APC 1990-2008 = 2.1, 95% CI = 0.6 to 3.6),
      thyroid cancer (Filipinas: APC 1990-2008 = 2.5, 95% CI = 1.7 to 3.3), and breast
      cancer in most groups (APC 1990-2008 from 1.2 among Vietnamese and Chinese to 4.7
      among Koreans). Decreases were observed for stomach (Chinese and Japanese),
      colorectal (Chinese), and cervical cancers (Laotians and Vietnamese).
      CONCLUSIONS: These data fill a critical knowledge gap concerning the cancer
      experience of Asian American groups and highlight where increased preventive,
      screening, and surveillance efforts are needed-in particular, lung cancer among
      Filipina and Korean women and Asian Indian/Pakistani men, breast cancer among all
      women, and liver cancer among Vietnamese, Laotian, and Kampuchean women and
      Filipino, Kampuchean, and Vietnamese men.

PMID- 23878352
TI  - Microsatellite instability and BRAF mutation testing in colorectal cancer
      prognostication.
AB  - BRAF mutation in colorectal cancer is associated with microsatellite instability
      (MSI) through its relationship with high-level CpG island methylator phenotype
      (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are
      routinely used for familial cancer risk assessment. To clarify clinical outcome
      associations of combined MSI/BRAF subgroups, we investigated survival in 1253
      rectal and colon cancer patients within the Nurses' Health Study and Health
      Professionals Follow-up Study with available data on clinical and other molecular
      features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations.
      Compared with the majority subtype of microsatellite stable (MSS)/BRAF-wild-type,
      MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF-wild-type subtypes
      showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60
      (95% confidence interval [CI] =1.12 to 2.28; P = .009), 0.48 (95% CI = 0.27 to
      0.87; P = .02), and 0.25 (95% CI = 0.12 to 0.52; P < .001), respectively. No
      evidence existed for a differential prognostic role of BRAF mutation by MSI
      status (P(interaction) > .50). Combined BRAF/MSI status in colorectal cancer is a
      tumor molecular biomarker for prognosic risk stratification.

PMID- 23878353
TI  - Cancer incidence among specific Asian and Pacific Islander populations in the
      Unites States.

PMID- 23878355
TI  - Advanced prostate cancer risk in relation to toenail selenium levels.
AB  - BACKGROUND: Selenium may prevent advanced prostate cancer (PCa), but most studies
      on this topic were conducted in populations with moderate to high selenium
      status. We investigated the association of toenail selenium, reflecting long-term
      selenium exposure, and advanced PCa risk in a population from the Netherlands
      where low selenium status is widespread. METHODS: The analysis was conducted in
      the prospective Netherlands Cohort Study, which included 58 279 men aged 55 to 69
      years at baseline in 1986. All cohort members completed a baseline questionnaire,
      and approximately 79% of participants provided toenail clippings, which were used
      for toenail selenium measurements using instrumental neutron activation analysis.
      Incident advanced PCa case subjects from the entire cohort were identified during
      17.3 years of follow-up. The study employed a case-cohort design for which a
      random subcohort was sampled at baseline. Hazard ratios and 95% confidence
      intervals (CIs) were estimated using Cox proportional hazards regression models.
      All tests were two-sided. RESULTS: Complete toenail selenium data were available
      for 898 advanced (International Union Against Cancer stage III/IV) PCa case
      subjects and 1176 subcohort members. The average toenail selenium concentration
      of subcohort members was 0.550 ug/g. Toenail selenium was associated with a
      reduced risk of advanced PCa; adjusted hazard ratio for the highest vs lowest
      quintile was 0.37 (95% CI = 0.27 to 0.51; P trend < .001). For stage IV PCa, men
      in the highest vs lowest quintile of toenail selenium had an adjusted hazard
      ratio of 0.30 (95% CI = 0.21 to 0.45; P trend < .001). CONCLUSIONS: Toenail
      selenium was associated with a substantial decrease in risk of advanced PCa.

PMID- 23878354
TI  - Cancer incidence trends among native Hawaiians and other Pacific Islanders in the
      United States, 1990-2008.
AB  - BACKGROUND: Lack of annual population estimates for disaggregated Native Hawaiian
      and Other Pacific Islander (NHOPI) populations limits the ability to examine
      cancer incidence rates and trends to understand the cancer burdens among NHOPIs.
      METHODS: Utilizing 1990 and 2000 population census data, we estimated the annual
      populations by age and sex for Native Hawaiians, Samoans, and
      Guamanians/Chamorros for 1990-2008 in regions covered by 13 of the National
      Cancer Institute's SEER registries. Cancer diagnoses during 1990-2008 from these
      registries were used to calculate the age-adjusted (2000 US Standard) incidence
      rates by sex, calendar year/period, and cancer type for each population. The
      annual percentage change (APC) in incidence rates was estimated with the 95%
      confidence intervals (95% CIs) calculated for both the rate and APC estimates.
      RESULTS: Statistically significant declining trends were found in Native
      Hawaiians, in men for lung and stomach cancers (APC = -2.3%; 95% CI = -3.3 to 
      1.3; and APC = -3.8%; 95% CI = -6.0 to -1.6, respectively), and in women for
      breast cancer (APC = -4.1%; 95% CI = -5.7 to -2.5) since 1998 and lung cancer
      (APC = -6.4%; 95% CI = -10.7 to -1.8) since 2001. Rising incidence trends were
      experienced by Samoans, especially by Samoan women for breast (APC = 2.7%; 95% CI
      = 0.9 to 4.5) and uterus (APC = 7.3%; 95% CI = 6.2 to 8.4) cancers. With limited
      data, Guamanians/Chamorros demonstrated lower, but increasing, incidence rates
      than other NHOPIs. CONCLUSIONS: Population-based cancer incidence rates for
      disaggregated NHOPI populations help identify disparities in cancer burden and
      provide valuable information to improve cancer control efforts among NHOPIs.

PMID- 23878356
TI  - Volumetric breast composition analysis: reproducibility of breast percent density
      and fibroglandular tissue volume measurements in serial mammograms.
AB  - BACKGROUND: Volumetric breast composition analysis represents a useful tool for
      assessing changes in breast composition over time. However, no data exist on the
      reproducibility of this method in serial mammograms. PURPOSE: To assess the
      reproducibility of two volumetric breast composition parameters, breast percent
      density (PD) and fibroglandular tissue volume (FTV), in consecutive mammograms.
      MATERIAL AND METHODS: Volumetric breast composition analysis to determine PD and
      FTV was performed in two consecutive unilateral mammograms of 211 patients. All
      mammograms were obtained on the same digital mammography unit within a maximum
      interval of 24 months. Volumetric data for analysis for both examinations were
      available for 174 patients. Thirty-two patients had successful volumetric
      analysis of additional consecutive examinations on a second digital mammography
      unit. Inter-examination correlation of measurements and absolute differences were
      analyzed. Bland-Altman analysis was performed to compare readings from different
      mammography units. RESULTS: Mean FTV remained constant over the study period. A
      reduction in PD of 0.5% and a mean increase in breast volume (BV) of 3% were
      observed. FTV measurements obtained on the same mammography unit were
      significantly more reproducible than PD measurements (Pearson correlation
      coefficients of 0.947 and 0.920, respectively; P < 0.05). A 15% difference
      between mean absolute volume measurements (FTV and BV) obtained on different
      mammography units was observed (P <= 0.001), while mean PD was close to the
      expected value. CONCLUSION: Volumetric breast composition analysis is highly
      reproducible in serial mammograms in normal women. FTV is a more reproducible
      parameter than PD, indicating that absolute quantification of breast parenchyma
      may be preferable to the measurement of relative parameters such as PD. However,
      a disadvantage of using FTV is that it is susceptible to systematic differences
      when measurements are obtained on different imaging platforms.

PMID- 23878357
TI  - The prevalence of osteoarthritis of the atlanto-odontoid joint in adults using
      multidetector computed tomography.
AB  - BACKGROUND: The prevalence of osteoarthritis of the atlanto-odontoid joint has
      been reported by radiology, autopsy, and conventional computed tomography (CT),
      but the prevalence has not yet been assessed by multidetector computed tomography
      (MDCT). PURPOSE: To reveal the prevalence of osteoarthritis of the atlanto
      odontoid joint and to analyze the inter-relationships among gender, age, and
      osteoarthritis with MDCT in adults. MATERIAL AND METHODS: First, a series of 700
      selected domestic patients aged >18 years undergoing an upper cervical MDCT scan
      were divided equally into seven age groups. Second, using the postprocessing
      technique of multiplanar reconstruction, osteoarthritis of the atlanto-odontoid
      joint was viewed from any direction and classified into four grades, which were
      normal, mild, moderate, and severe. Lastly, the incidence of the different grades
      of osteoarthritis was assessed, and the reproducibility was tested. RESULTS:
      There was no significant difference between gender and osteoarthritis of atlanto
      odontoid joint (P > 0.05). The rate of osteoarthritis was 16% in the age group 18
      25 years, 23% in the age group 25-30 years, 33% in the age group 30-40 years, 54%
      in the age group 40-50 years, 70% in the age group 50-60 years, 87% in the age
      group 60-70 years, and 93% in the age group >70 years. Mild osteoarthritis
      appeared at the earliest at age 19.6 years, moderate osteoarthritis in at
      earliest at age 24.2 years, and severe osteoarthritis at the earliest at age 48.5
      years. The inter-observer reliability was excellent (k = 0.86). CONCLUSION:
      Osteoarthritis of the atlanto-odontoid joint could be detected by MDCT in a young
      adult. It increased rapidly with increasing age on MDCT.

PMID- 23878358
TI  - Diffusion-weighted magnetic resonance imaging combined with T2-weighted images in
      the detection of small breast cancer: a single-center multi-observer study.
AB  - BACKGROUND: Breast cancer is the most common cancer in women worldwide. However,
      it remains a difficult diagnosis problem to differentiate between benign and
      malignant breast lesions, especially in small early breast lesions. PURPOSE: To
      assess the diagnostic value of diffusion-weighted imaging (DWI) combined with T2
      weighted imaging (T2WI) for small breast cancer characterization. MATERIAL AND
      METHODS: Fifty-eight patients (65 lesions) with a lesion <2 cm in diameter
      underwent 3.0 Tesla breast magnetic resonance imaging (MRI) including DWI and
      histological analysis. Three observers with varying experience levels reviewed
      MRI. The probability of breast cancer in each lesion on MR images was recorded
      with a 5-point scale. Areas under the receiver-operating characteristic curve
      (AUCs) were compared by using the Z test; sensitivity and specificity were
      determined with the Z test after adjusting for data clustering. RESULTS: AUC of
      T2WI and DWI (Observer 1, 0.95; Observer 2, 0.91; Observer 3, 0.83) was greater
      than that of T2WI (Observer 1, 0.80; Observer 2, 0.74; Observer 3, 0.70) for all
      observers (P < 0.0001 in all comparisons). Sensitivity of T2WI and DWI (Observer
      1, 90%; Observer 2, 93%; and Observer 3, 86%) was greater than that of T2WI alone
      (Observer 1, 76%; Observer 2, 83%; Observer 3, 79%) for all observers (P < 0.0001
      in all comparisons). Specificity of T2WI and DWI was greater than that of T2WI
      alone for observer 1 (89% vs. 72%, P < 0.01) and observer 2 (94% vs. 78%, P <
      0.001). CONCLUSION: DWI combined with T2WI can improve the diagnostic performance
      of MRI in small breast cancer characterization. It should be considered
      selectively in the preoperative evaluation of patients with small lesions of the
      breast.

PMID- 23878359
TI  - Discriminative analysis of early-stage Alzheimer's disease and normal aging with
      automatic segmentation technique in subcortical gray matter structures: a
      multicenter in vivo MRI volumetric and DTI study.
AB  - BACKGROUND: Previous studies have revealed that amyloid depositions exist in not
      only the hippocampus but in other subcortical gray matter structures as well.
      Diffusion-tensor imaging (DTI) parameters might be more sensitive measures of
      early degeneration in Alzheimer's disease (AD) than conventional magnetic
      resonance imaging (MRI) techniques. PURPOSE: To evaluate the significance of the
      volumes and the mean diffusivity (MD) values of subcortical gray matter
      structures in discrimination between early-stage AD and normal subjects using the
      Integrated Registration and Segmentation Tool in FMRIB's Software Library.
      MATERIAL AND METHODS: Fifty-three cases of early-stage AD and 30 normal aging
      volunteers from two hospitals were scanned with 3D-FSPGRIR and SSSE-EPI sequences
      using two similar 1.5T MR systems. The mean relative volumes and mean MD values
      of subcortical gray matter structures were compared between early-stage AD and
      control groups. Binary logistic regression analysis and receiver-operating
      characteristic (ROC) curves were applied to assess the diagnostic significance of
      every structure's relative volume, MD value, and combination of both. RESULTS:
      The relative volumes of the left hippocampus, right amygdala, bilateral thalamus,
      right caudate, left putamen, and bilateral pallidum were significantly lower in
      the early-stage AD group than in the control group (P < 0.05). The MD values of
      the bilateral hippocampus and pallidum, and of the right thalamus and caudate
      were significantly elevated in the early-stage AD group (P < 0.05). In binary
      logistic regression analysis, the relative volume of left hippocampus and age
      entered the final model of volumetric analysis. The MD values of bilateral
      hippocampi and pallidums entered the final model of MD analysis. The MD values of
      bilateral hippocampi and pallidums, and the relative volume of left pallidum,
      entered the final model of combination analysis. The accuracy of three models was
      84.7%, 88.9%, and 93.1%, respectively. CONCLUSION: Pathological changes takes
      place in the hippocampus and other subcortical gray matter structures in early
      stage AD. Diffusive imaging has great diagnostic significance in early-stage AD.
      The combination of both imaging modalities can lead to better discrimination
      between early-stage AD and normal aging.

PMID- 23878360
TI  - 3-T in-bore MR-guided prostate biopsy based on a scoring system for target
      lesions characterization.
AB  - BACKGROUND: To estimate potential malignant lesions within the prostate gland,
      the usage of a scoring system has recently been proposed by a European consensus
      meeting. PURPOSE: To prospectively investigate a scoring system for functional
      prostate magnetic resonance imaging (MRI) using in-bore MR-guided prostate biopsy
      at 3-T. MATERIAL AND METHODS: Prostate MRI examinations of 59 patients (between
      February 2011 and May 2012) with no known prostate cancer, elevated prostate
      specific antigen (PSA) level, and unsuspicious digital rectal examination were
      included in the study. In each patient up to three lesions were defined and
      scored using a 5-point scoring system for each MR sequence (T2-weighted images,
      diffusion-weighted imaging, dynamic contrast-enhanced imaging). Following MRI
      guided in-bore biopsy these lesions were correlated to the histopathological
      findings. RESULTS: A total number of 144 lesions were defined in 59 patients. In
      28 patients (51 lesions) MR-guided in-bore biopsy was positive for tumor (Gleason
      grade 6 or higher). A cut-off limit of 10 or more points in summation of the
      individual scores of all three sequences was used, leading to a 90% sensitivity,
      63% specificity, 58% positive predictive value, and 92% negative predictive
      value. CONCLUSION: A simple 5-point scoring system of functional prostate MRI
      achieves excellent sensitivity and moderate specificity for directing 3-T-guided
      prostate biopsy relative to the histopathological findings.

PMID- 23878361
TI  - Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive
      lipase in skeletal muscle.
AB  - In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be
      the principal enzyme responsible for lipolysis of intramyocellular
      triacylglycerol (IMTG) during contractions. However, this notion is based on in
      vitro lipase activity data, which may not reflect the in vivo lipolytic activity.
      We investigated lipolysis of IMTG in soleus muscles electrically stimulated to
      contract ex vivo during acute pharmacological inhibition of HSL in rat muscles
      and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are
      complicated by the presence of adipocytes located between the muscle fibres. To
      circumvent the problem with this contamination we analysed intramyocellular lipid
      droplet content histochemically. At maximal inhibition of HSL in rat muscles,
      contraction-induced breakdown of IMTG was identical to that seen in control
      muscles (P < 0.001). In response to contractions IMTG staining decreased
      significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase
      activity data revealed that adipose triglyceride lipase (ATGL) and HSL
      collectively account for ~98% of the TG hydrolase activity in mouse skeletal
      muscle, other TG lipases accordingly being of negligible importance for lipolysis
      of IMTG. The present study is the first to demonstrate that contraction-induced
      lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal
      muscle. Furthermore, the results suggest that ATGL is activated and plays a major
      role in lipolysis of IMTG during muscle contractions.

PMID- 23878362
TI  - Does epithelial sodium channel hyperactivity contribute to cystic fibrosis lung
      disease?
AB  - Airway epithelia absorb Na+ through the epithelial Na+ channel (ENaC) and
      secrete Cl- through the cystic fibrosis transmembrane conductance regulator
      (CFTR) anion channel. This balance maintains sufficient airway surface liquid
      hydration to permit efficient mucus clearance, which is needed to maintain
      sterility of the lung. Cystic fibrosis (CF) is a common autosomal recessive
      inherited disease caused by mutations in the CFTR gene that lead to the reduction
      or elimination of the CFTR protein. CF is a multi-organ disease that affects
      epithelia lining the intestines, lungs, pancreas, sweat ducts and vas deferens,
      among others. CF lungs are characterized by viscous, dehydrated mucus, persistent
      neutrophilia and chronic infections. ENaC is negatively regulated by CFTR and, in
      patients with CF, the absence of CFTR results in a double hit of reduced Cl-/HCO3
      and H2O secretion as well as ENaC hyperactivity and increased Na+ and H2O
      absorption. Together, these effects are hypothesized to trigger mucus
      dehydration, resulting in a failure to clear mucus. Rehydrating CF mucus has
      become a recent clinical focus and yields important end-points for clinical
      trials. However, while ENaC hyperactivity in CF airways has been detected in vivo
      and in vitro, recent data have brought the role of ENaC in CF lung disease
      pathogenesis into question. This review will focus on our current understanding
      of the contribution of ENaC to CF pathogenesis.

PMID- 23878363
TI  - Myths and realities of the cardiac vagus.
AB  - There is continuing belief that cardiac parasympathetic postganglionic fibres are
      sparse or absent from the ventricles. This review of the literature shows that
      the supposition is a myth. Early studies considered that fine silver-stained
      fibres coursing amongst ventricle myocardial cells were most likely cardiac
      parasympathetic postganglionic fibres. The conclusions were later supported by
      acetyl cholinesterase staining using a method that appeared not to be associated
      with noradrenaline nerve fibres. The conclusion is critically examined in the
      light of several recent histological studies using the acetyl cholinesterase
      method and also a more definitive technique (CHAT), that suggest a widespread
      location of parasympathetic ganglia and a relatively dense parasympathetic
      innervation of ventricular muscle in a range of mammals including man. The many
      studies demonstrating acetylcholine release in the ventricle on vagal nerve
      stimulation and a high density of acetylcholine M2 receptors is in accord with
      this as are tests of ventricular performance from many physiological studies.
      Selective control of cardiac functions by anatomically segregated parasympathetic
      ganglia is discussed. It is argued that the influence of vagal stimulation on
      ventricular myocardial action potential refractory period, duration, force and
      rhythm is evidence that vagal fibres have close apposition to myocardial fibres.
      This is supported by clear evidence of accentuated antagonism between sympathetic
      activity and vagal activity in the ventricle and also by direct effects of vagal
      activity independent of sympathetic activity. The idea of differential control of
      atrial and ventricular physiology by vagal C and vagal B preganglionic fibres is
      examined as well as differences in chemical phenotypes and their function. The
      latter is reflected in medullary and supramedullary control. Reference is made to
      the importance of this knowledge to understanding the normal physiology of
      cardiac autonomic control and significance to pathology.

PMID- 23878364
TI  - Intrauterine inflammation alters fetal cardiopulmonary and cerebral haemodynamics
      in sheep.
AB  - Intrauterine inflammation impairs fetal pulmonary vascular development and
      increases cerebral metabolic rate in fetal sheep. We hypothesized that these
      structural and metabolic effects of intrauterine inflammation would be
      accompanied by reduced fetal pulmonary blood flow and increased cerebral
      perfusion. Fetal sheep were instrumented at 112 days of gestation (term is 147
      days) for measurement of cardiopulmonary and cerebral haemodynamics. At 118 days
      ewes were randomly assigned to receive intra-amniotic lipopolysaccharide (LPS, 20
      mg from Escherichia coli; n = 7) or saline (control, 4 ml; n = 6). Fetal
      haemodynamic data were recorded continually from 1 h before intra-amniotic LPS or
      saline, until 144 h after. Fetal arterial blood was sampled before, and
      periodically after, intra-amniotic LPS or saline. End-diastolic and mean
      pulmonary blood flows were significantly lower than control from 48 and 96 h
      after LPS exposure, respectively, until the end of the experiment. Carotid blood
      flow was transiently increased at 96 and 120 h after LPS exposure. Carotid
      arterial oxygen content was lower than control from 48 h after intra-amniotic
      LPS. Fetal arterial lactate concentration was higher than control between 4 and
      12 h after intra-amniotic LPS. Experimental intrauterine inflammation reduces
      pulmonary blood flow in fetal sheep, over a time course consistent with impaired
      pulmonary vascular development. Increased carotid blood flow after LPS
      administration may reflect an inflammation-induced increase in cerebral metabolic
      demand.

PMID- 23878365
TI  - Activity and distribution of intracellular carbonic anhydrase II and their
      effects on the transport activity of anion exchanger AE1/SLC4A1.
AB  - We have investigated the previously published 'metabolon hypothesis' postulating
      that a close association of the anion exchanger 1 (AE1) and cytosolic carbonic
      anhydrase II (CAII) exists that greatly increases the transport activity of AE1.
      We study whether there is a physical association of and direct functional
      interaction between CAII and AE1 in the native human red cell and in tsA201 cells
      coexpressing heterologous fluorescent fusion proteins CAII-CyPet and YPet-AE1. In
      these doubly transfected tsA201 cells, YPet-AE1 is clearly associated with the
      cell membrane, whereas CAII-CyPet is homogeneously distributed throughout the
      cell in a cytoplasmic pattern. Forster resonance energy transfer measurements
      fail to detect close proximity of YPet-AE1 and CAII-CyPet. The absence of an
      association of AE1 and CAII is supported by immunoprecipitation experiments using
      Flag-antibody against Flag-tagged AE1 expressed in tsA201 cells, which does not
      co-precipitate native CAII but co-precipitates coexpressed ankyrin. Both the CAII
      and the AE1 fusion proteins are fully functional in tsA201 cells as judged by CA
      activity and by cellular HCO3(-) permeability (P(HCO3(-))) sensitive to
      inhibition by 4,4-Diisothiocyano-2,2-stilbenedisulfonic acid. Expression of the
      non-catalytic CAII mutant V143Y leads to a drastic reduction of endogenous CAII
      and to a corresponding reduction of total intracellular CA activity.
      Overexpression of an N-terminally truncated CAII lacking the proposed site of
      interaction with the C-terminal cytoplasmic tail of AE1 substantially increases
      intracellular CA activity, as does overexpression of wild-type CAII. These
      variously co-transfected tsA201 cells exhibit a positive correlation between
      cellular P(HCO3(-)) and intracellular CA activity. The relationship reflects that
      expected from changes in cytoplasmic CA activity improving substrate supply to or
      removal from AE1, without requirement for a CAII-AE1 metabolon involving physical
      interaction. A functional contribution of the hypothesized CAII-AE1 metabolon to
      erythroid AE1-mediated HCO3(-) transport was further tested in normal red cells
      and red cells from CAII-deficient patients that retain substantial CA activity
      associated with the erythroid CAI protein lacking the proposed AE1-binding
      sequence. Erythroid P(HCO3(-)) was indistinguishable in these two cell types,
      providing no support for the proposed functional importance of the physical
      interaction of CAII and AE1. A theoretical model predicts that homogeneous
      cytoplasmic distribution of CAII is more favourable for cellular transport of
      HCO3(-) and CO2 than is association of CAII with the cytoplasmic surface of the
      plasma membrane. This is due to the fact that the relatively slow intracellular
      transport of H(+) makes it most efficient to place the CA in the vicinity of the
      haemoglobin molecules, which are homogeneously distributed over the cytoplasm.

PMID- 23878366
TI  - Neuronal major histocompatibility complex class I molecules are implicated in the
      generation of asymmetries in hippocampal circuitry.
AB  - Left-right asymmetry is a fundamental feature of higher-order brain function;
      however, the molecular basis of brain asymmetry has remained unclear. We have
      recently demonstrated asymmetries in hippocampal circuitry resulting from the
      asymmetrical allocation of NMDA receptor (NMDAR) subunit GluR2 (NR2B) in
      pyramidal cell synapses. This asymmetrical allocation of 2 subunits affects the
      properties of NMDARs and generates two populations of synapses, '2-dominant' and
      '2-non-dominant' synapses, according to the hemispheric origin of presynaptic
      inputs and cell polarity of the postsynaptic neurone. To identify key regulators
      for generating asymmetries, we analysed the hippocampus of beta2-microglobulin
      (beta2m)-deficient mice lacking cell surface expression of major
      histocompatibility complex class I (MHCI). Although MHCI proteins are well known
      in the immune system, accumulating evidence indicates that MHCI proteins are
      expressed in the brain and are required for activity-dependent refinement of
      neuronal connections and normal synaptic plasticity. We found that beta2m
      proteins were localised in hippocampal synapses in wild-type mice. NMDA EPSCs in
      beta2m-deficient hippocampal synapses receiving inputs from both hemispheres
      showed similar sensitivity to Ro 25-6981, an 2 subunit-selective antagonist, with
      those in '2-dominant' synapses for both the apical and basal synapses of
      pyramidal neurones. The structural features of the beta2m-deficient synapse in
      addition to the relationship between the stimulation frequency and synaptic
      plasticity were also comparable to those of '2-dominant' synapses. These
      observations indicate that the beta2m-deficient hippocampus lacks '2-non
      dominant' synapses and circuit asymmetries. Our findings provide evidence
      supporting a critical role of MHCI molecules for generating asymmetries in
      hippocampal circuitry.

PMID- 23878367
TI  - A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of
      glucocorticoids in mammalian skeletal muscle fibres.
AB  - Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in
      response to stress. They are also some of the most potent anti-inflammatory and
      immunosuppressive drugs currently in clinical use. They exert most of their
      physiological and pharmacological actions through the classical/genomic pathway.
      However, they also have rapid/non-genomic actions whose physiological and
      pharmacological functions are still poorly understood. Therefore, the primary aim
      of this study was to investigate the rapid/non-genomic effects of two widely
      prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone
      acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle
      fibre bundles. The results show that the effects of both GCs on maximum isometric
      force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch
      fibre bundles without significantly affecting that of the fast-twitch fibre
      bundles. The increase in Po occurred within 10 min and was insensitive to the
      transcriptional inhibitor actinomycin D. Also, it was maximal at ~250 nM and was
      blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal
      anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle
      fibre types expressed a cytosolic GCR. However, a mGCR was present only in the
      slow-twitch fibres. The receptor was more abundant in oxidative than in
      glycolytic fibres and was confined mainly to the periphery of the fibres where it
      co-localised with laminin. From these findings we conclude that the rapid/non
      genomic actions of GCs are mediated by a mGCR and that they are
      physiologically/therapeutically beneficial, especially in slow-twitch muscle
      fibres.

PMID- 23878368
TI  - Resveratrol blunts the positive effects of exercise training on cardiovascular
      health in aged men.
AB  - Ageing is thought to be associated with decreased vascular function partly due to
      oxidative stress. Resveratrol is a polyphenol, which in animal studies has been
      shown to decrease atherosclerosis, and improve cardiovascular health and physical
      capacity, in part through its effects on Sirtuin 1 signalling and through an
      improved antioxidant capacity. We tested the hypothesis that resveratrol
      supplementation enhances training-induced improvements in cardiovascular health
      parameters in aged men. Twenty-seven healthy physically inactive aged men (age:
      65 +/- 1 years; body mass index: 25.4 +/- 0.7 kg m(-2); mean arterial pressure
      (MAP): 95.8 +/- 2.2 mmHg; maximal oxygen uptake: 2488 +/- 72 ml O2 min(-1)) were
      randomized into 8 weeks of either daily intake of either 250 mg trans-resveratrol
      (n = 14) or of placebo (n = 13) concomitant with high-intensity exercise
      training. Exercise training led to a 45% greater (P < 0.05) increase in maximal
      oxygen uptake in the placebo group than in the resveratrol group and to a
      decrease in MAP in the placebo group only (-4.8 +/- 1.7 mmHg; P < 0.05). The
      interstitial level of vasodilator prostacyclin was lower in the resveratrol than
      in the placebo group after training (980 +/- 90 vs. 1174 +/- 121 pg ml(-1); P <
      0.02) and muscle thromboxane synthase was higher in the resveratrol group after
      training (P < 0.05). Resveratrol administration also abolished the positive
      effects of exercise on low-density lipoprotein, total cholesterol/high-density
      lipoprotein ratio and triglyceride concentrations in blood (P < 0.05).
      Resveratrol did not alter the effect of exercise training on the atherosclerosis
      marker vascular cell adhesion molecule 1 (VCAM-1). Sirtuin 1 protein levels were
      not affected by resveratrol supplementation. These findings indicate that,
      whereas exercise training effectively improves several cardiovascular health
      parameters in aged men, concomitant resveratrol supplementation can blunt these
      effects.

PMID- 23878369
TI  - Temporal response of positive and negative regulators in response to acute and
      chronic exercise training in mice.
AB  - Angiogenesis is controlled by a balance between positive and negative angiogenic
      factors, but temporal protein expression of many key angiogenic regulators in
      response to exercise are still poorly defined. In C57BL/6 mice, we evaluated the
      temporal protein expression of several pro-angiogenic and anti-angiogenic factors
      in response to (1) a single acute bout of exercise and (2) chronic exercise
      training resulting from 3, 5, 7, 14 and 28 days of voluntary wheel running.
      Following acute exercise, protein levels of vascular endothelial growth factor-A
      (VEGF), endostatin and nucleolin were increased at 2-4 h (P < 0.05), whereas
      matrix metalloproteinase (MMP)-2 was elevated within a 12-24 h window (P < 0.05).
      Training increased muscle capillarity 11%, 15% and 22% starting with 7, 14 and 28
      days of training, respectively (P < 0.01). Basal VEGF and MMP-2 were increased by
      31% and 22%, respectively, compared to controls (P < 0.05) after 7 days (7d)
      training, but decreased to back to baseline after 14d training. After 28d
      training VEGF fell 49% below baseline control (P < 0.01). Basal muscle expression
      of thrombospondin 1 (TSP-1) was ~900% greater in 14d- and 28d-trained mice
      compared to either 5d- and 7d-trained mice (P < 0.05), and tended to increase by
      ~180-258% compared to basal control levels (P < 0.10). The acute responsiveness
      of VEGF to exercise in untrained mice (i.e. 161% increase, P < 0.001) was lost
      with capillary adaptation occurring after 7, 14 and 28d training. Taken together,
      these data support the notion that skeletal muscle angiogenesis is controlled by
      a balance between positive and negative mitogens, and reveals a complex, highly
      coordinated, temporal scheme whereby these factors can differentially influence
      capillary growth in response to acute versus chronic exercise.

PMID- 23878370
TI  - Spinal TNF is necessary for inactivity-induced phrenic motor facilitation.
AB  - A prolonged reduction in central neural respiratory activity elicits a form of
      plasticity known as inactivity-induced phrenic motor facilitation (iPMF), a
      'rebound' increase in phrenic burst amplitude apparent once respiratory neural
      activity is restored. iPMF requires atypical protein kinase C (aPKC) activity
      within spinal segments containing the phrenic motor nucleus to stabilize an early
      transient increase in phrenic burst amplitude and to form long-lasting iPMF
      following reduced respiratory neural activity. Upstream signal(s) leading to
      spinal aPKC activation are unknown. We tested the hypothesis that spinal tumour
      necrosis factor-alpha (TNFalpha) is necessary for iPMF via an aPKC-dependent
      mechanism. Anaesthetized, ventilated rats were exposed to a 30 min neural apnoea;
      upon resumption of respiratory neural activity, a prolonged increase in phrenic
      burst amplitude (42 +/- 9% baseline; P < 0.05) was apparent, indicating long
      lasting iPMF. Pretreatment with recombinant human soluble TNF receptor 1 (sTNFR1)
      in the intrathecal space at the level of the phrenic motor nucleus prior to
      neural apnoea blocked long-lasting iPMF (2 +/- 8% baseline; P > 0.05).
      Intrathecal TNFalpha without neural apnoea was sufficient to elicit long-lasting
      phrenic motor facilitation (pMF; 62 +/- 7% baseline; P < 0.05). Similar to iPMF,
      TNFalpha-induced pMF required spinal aPKC activity, as intrathecal delivery of a
      zeta-pseudosubstrate inhibitory peptide (PKCzeta-PS) 35 min following intrathecal
      TNFalpha arrested TNFalpha-induced pMF (28 +/- 8% baseline; P < 0.05). These data
      demonstrate that: (1) spinal TNFalpha is necessary for iPMF; and (2) spinal
      TNFalpha is sufficient to elicit pMF via a similar aPKC-dependent mechanism.
      These data are consistent with the hypothesis that reduced respiratory neural
      activity elicits iPMF via a TNFalpha-dependent increase in spinal aPKC activity.

PMID- 23878371
TI  - Aldosterone increases cardiac vagal tone via G protein-coupled oestrogen receptor
      activation.
AB  - In addition to acting on mineralocorticoid receptors, aldosterone has been
      recently shown to activate the G protein-coupled oestrogen receptor (GPER) in
      vascular cells. In light of the newly identified role for GPER in vagal cardiac
      control, we examined whether or not aldosterone activates GPER in rat nucleus
      ambiguus. Aldosterone produced a dose-dependent increase in cytosolic Ca(2+)
      concentration in retrogradely labelled cardiac vagal neurons of nucleus ambiguus;
      the response was abolished by pretreatment with the GPER antagonist G-36, but was
      not affected by the mineralocorticoid receptor antagonists, spironolactone and
      eplerenone. In Ca(2+)-free saline, the response to aldosterone was insensitive to
      blockade of the Ca(2+) release from lysosomes, while it was reduced by blocking
      the Ca(2+) release via ryanodine receptors and abolished by blocking the IP3
      receptors. Aldosterone induced Ca(2+) influx via P/Q-type Ca(2+) channels, but
      not via L-type and N-type Ca(2+) channels. Aldosterone induced depolarization of
      cardiac vagal neurons of nucleus ambiguus that was sensitive to antagonism of
      GPER but not of mineralocorticoid receptor. in vivo studies, using telemetric
      measurement of heart rate, indicate that microinjection of aldosterone into the
      nucleus ambiguus produced a dose-dependent bradycardia in conscious, freely
      moving rats. Aldosterone-induced bradycardia was blocked by the GPER antagonist,
      but not by the mineralocorticoid receptor antagonists. In summary, we report for
      the first time that aldosterone decreases heart rate by activating GPER in
      cardiac vagal neurons of nucleus ambiguus.

PMID- 23878372
TI  - Mechanisms of retroaxonal barrage firing in hippocampal interneurons.
AB  - We recently described a new form of neural integration and firing in a subset of
      interneurons, in which evoking hundreds of action potentials over tens of seconds
      to minutes produces a sudden barrage of action potentials lasting about a minute
      beyond the inciting stimulation. During this persistent firing, action potentials
      are generated in the distal axon and propagate retrogradely to the soma. To
      distinguish this from other forms of persistent firing, we refer to it here as
      'retroaxonal barrage firing', or 'barrage firing' for short. Its induction is
      blocked by chemical inhibitors of gap junctions and curiously, stimulation of one
      interneuron in some cases triggers barrage firing in a nearby, unstimulated
      interneuron. Beyond these clues, the mechanisms of barrage firing are unknown.
      Here we report new results related to these mechanisms. Induction of barrage
      firing was blocked by lowering extracellular calcium, as long as normal action
      potential threshold was maintained, and it was inhibited by blocking L-type
      voltage-gated calcium channels. Despite its calcium dependence, barrage firing
      was not prevented by inhibiting chemical synaptic transmission. Furthermore,
      loading the stimulated/recorded interneuron with BAPTA did not block barrage
      firing, suggesting that the required calcium entry occurs in other cells.
      Finally, barrage firing was normal in mice with deletion of the primary gene for
      neuronal gap junctions (connexin36), suggesting that non-neuronal gap junctions
      may be involved. Together, these findings suggest that barrage firing is probably
      triggered by a multicellular mechanism involving calcium signalling and gap
      junctions, but operating independently of chemical synaptic transmission.

PMID- 23878373
TI  - Kv2 channels regulate firing rate in pyramidal neurons from rat sensorimotor
      cortex.
AB  - The largest outward potassium current in the soma of neocortical pyramidal
      neurons is due to channels containing Kv2.1 alpha subunits. These channels have
      been implicated in cellular responses to seizures and ischaemia, mechanisms for
      intrinsic plasticity and cell death, and responsiveness to anaesthetic agents.
      Despite their abundance, knowledge of the function of these delayed rectifier
      channels has been limited by the lack of specific pharmacological agents. To test
      for functional roles of Kv2 channels in pyramidal cells from somatosensory or
      motor cortex of rats (layers 2/3 or 5), we transfected cortical neurons with DNA
      for a Kv2.1 pore mutant (Kv2.1W365C/Y380T: Kv2.1 DN) in an organotypic culture
      model to manipulate channel expression. Slices were obtained from rats at
      postnatal days (P7-P14) and maintained in organotypic culture. We used biolistic
      methods to transfect neurons with gold 'bullets' coated with DNA for the Kv2.1 DN
      and green fluorescent protein (GFP), GFP alone, or wild type (WT) Kv2.1 plus GFP.
      Cells that fluoresced green, contained a bullet and responded to positive or
      negative pressure from the recording pipette were considered to be transfected
      cells. In each slice, we recorded from a transfected cell and a control non
      transfected cell from the same layer and area. Whole-cell voltage-clamp
      recordings obtained after 3-7 days in culture showed that cells transfected with
      the Kv2.1 DN had a significant reduction in outward current (~45% decrease in the
      total current density measured 200 ms after onset of a voltage step from -78 to 
      2 mV). Transfection with GFP alone did not affect current amplitude and
      overexpression of the Kv2.1 WT resulted in greatly increased currents. Current
      clamp experiments were used to assess the functional consequences of manipulation
      of Kv2.1 expression. The results suggest roles for Kv2 channels in controlling
      membrane potential during the interspike interval (ISI), firing rate, spike
      frequency adaptation (SFA) and the steady-state gain of firing. Specifically,
      firing rate and gain were reduced in the Kv2.1 DN cells. The most parsimonious
      explanation for the effects on firing is that in the absence of Kv2 channels, the
      membrane remains depolarized during the ISIs, preventing recovery of Na(+)
      channels from inactivation. Depolarization and the number of inactivated Na(+)
      channels would build with successive spikes, resulting in slower firing and
      enhanced spike frequency adaptation in the Kv2.1 DN cells.

PMID- 23878374
TI  - The working stroke of the myosin II motor in muscle is not tightly coupled to
      release of orthophosphate from its active site.
AB  - Skeletal muscle shortens faster against a lower load. This force-velocity
      relationship is the fundamental determinant of muscle performance in vivo and is
      due to ATP-driven working strokes of myosin II motors, during their cyclic
      interactions with the actin filament in each half-sarcomere. Crystallographic
      studies suggest that the working stroke is associated with the release of
      phosphate (Pi) and consists of 70 deg tilting of a light-chain domain that
      connects the catalytic domain of the myosin motor to the myosin tail and
      filament. However, the coupling of the working stroke with Pi release is still an
      unsolved question. Using nanometre-microsecond mechanics on skinned muscle
      fibres, we impose stepwise drops in force on an otherwise isometric contraction
      and record the isotonic velocity transient, to measure the mechanical
      manifestation of the working stroke of myosin motors and the rate of its
      regeneration in relation to the half-sarcomere load and [Pi]. We show that the
      rate constant of the working stroke is unaffected by [Pi], while the subsequent
      transition to steady velocity shortening is accelerated. We propose a new chemo
      mechanical model that reproduces the transient and steady state responses by
      assuming that: (i) the release of Pi from the catalytic site of a myosin motor
      can occur at any stage of the working stroke, and (ii) a myosin motor, in an
      intermediate state of the working stroke, can slip to the next actin monomer
      during filament sliding. This model explains the efficient action of muscle
      molecular motors working as an ensemble in the half-sarcomere.

PMID- 23878376
TI  - How LeuT shapes our understanding of the mechanisms of sodium-coupled
      neurotransmitter transporters.
AB  - Neurotransmitter transporters are ion-coupled symporters that drive the uptake of
      neurotransmitters from neural synapses. In the past decade, the structure of a
      bacterial amino acid transporter, leucine transporter (LeuT), has given valuable
      insights into the understanding of architecture and mechanism of mammalian
      neurotransmitter transporters. Different conformations of LeuT, including a
      substrate-free state, inward-open state, and competitive and non-competitive
      inhibitor-bound states, have revealed a mechanistic framework for the transport
      and transport inhibition of neurotransmitters. The current review integrates our
      understanding of the mechanistic and pharmacological properties of eukaryotic
      neurotransmitter transporters obtained through structural snapshots of LeuT. 

PMID- 23878378
TI  - Stress at the second metatarsal bone after correction of hammertoe and claw toe
      deformity: a finite element analysis using an anatomical model.
AB  - BACKGROUND: We used finite element analysis to evaluate three techniques for the
      correction of hammertoe and claw toe deformities: flexor digitorum longus tendon
      transfer (FDLT), flexor digitorum brevis tendon transfer (FDBT), and proximal
      interphalangeal joint arthrodesis (PIPJA). METHODS: We performed a finite element
      analysis of FDLT and FDBT compared with PIPJA of the second toe using multislice
      computed tomography and 93 tomographic images of the foot obtained in a healthy
      36-year-old man. RESULTS: The PIPJA showed a significantly higher increase in
      traction and compressive stresses and strain at the medial aspect of the shaft of
      the second metatarsal bone compared with FDLT or FDBT (P < .01). Mean +/- SD
      compressive stresses increased to -4.35 +/- 7.05 MPa compared with the
      nonsurgical foot (-3.10 +/- 4.90 MPa). It can, therefore, be hypothesized that if
      PIPJA is used to correct the hammertoe and claw toe deformities, it could also
      increase traction and compressive stresses and strain in the metatarsals during
      running and other vigorous activities. CONCLUSIONS: There is a biomechanical
      advantage to performing FDLT or FDBT instead of PIPJA to surgically treat a
      hammertoe or claw toe deformity. In addition, tensile strain at the dorsal aspect
      of the second metatarsal bone when performing PIPJA increases the risk of
      metatarsalgia or stress fracture in patients at risk.

PMID- 23878377
TI  - Ionic mechanisms limiting cardiac repolarization reserve in humans compared to
      dogs.
AB  - The species-specific determinants of repolarization are poorly understood. This
      study compared the contribution of various currents to cardiac repolarization in
      canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp,
      molecular biological and mathematical modelling techniques were used. Selective
      IKr block (50-100 nmol l(-1) dofetilide) lengthened AP duration at 90% of
      repolarization (APD90) >3-fold more in human than dog, suggesting smaller
      repolarization reserve in humans. Selective IK1 block (10 MUmol l(-1) BaCl2) and
      IKs block (1 MUmol l(-1) HMR-1556) increased APD90 more in canine than human
      right ventricular papillary muscle. Ion current measurements in isolated
      cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in
      dogs than humans, respectively. IKr density and kinetics were similar in human
      versus dog. ICa and Ito were respectively ~30% larger and ~29% smaller in human,
      and Na(+)-Ca(2+) exchange current was comparable. Cardiac mRNA levels for the
      main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were
      significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKs alpha
      subunits) were not significantly different, in human versus dog. Immunostaining
      suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human
      versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging
      effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and
      16%), indicating that both currents contribute to increased repolarization
      reserve in the dog. A mathematical model incorporating observed human-canine ion
      current differences confirmed the role of IK1 and IKs in repolarization reserve
      differences. Thus, humans show greater repolarization-delaying effects of IKr
      block than dogs, because of lower repolarization reserve contributions from IK1
      and IKs, emphasizing species-specific determinants of repolarization and the
      limitations of animal models for human disease.

PMID- 23878375
TI  - Regulation of membrane trafficking by signalling on endosomal and lysosomal
      membranes.
AB  - Endosomal and lysosomal membrane trafficking requires the coordination of
      multiple signalling events to control cargo sorting and processing, and endosome
      maturation. The initiation and termination of signalling events in endosomes and
      lysosomes is not well understood, but several key regulators have been
      identified, which include small GTPases, phosphoinositides, and Ca2+. Small
      GTPases act as master regulators and molecular switches in a GTP-dependent
      manner, initiating signalling cascades to regulate the direction and specificity
      of endosomal trafficking. Phosphoinositides are membrane-bound lipids that
      indicate vesicular identities for recruiting specific cytoplasmic proteins to
      endosomal membranes, thus allowing specificity of membrane fusion, fission, and
      cargo sorting to occur within and between specific vesicle compartments. In
      addition, phosphoinositides regulate the function of membrane proteins such as
      ion channels and transporters in a compartment-specific manner to mediate
      transport and signalling. Finally, Ca2+, a locally acting second messenger
      released from intracellular ion channels, may provide precise spatiotemporal
      regulation of endosomal signalling and trafficking events. Small GTPase
      signalling can regulate phosphoinositide conversion during endosome maturation,
      and electrophysiological studies on isolated endosomes have shown that endosomal
      and lysosomal Ca2+ channels are directly modulated by endosomal lipids. Thus
      trafficking and maturation of endosomes and lysosomes can be precisely regulated
      by dynamic changes in GTPases and membrane lipids, as well as Ca2+ signalling.
      Importantly, impaired phosphoinositide and Ca2+ signalling can cause endosomal
      and lysosomal trafficking defects at the cellular level, and a spectrum of
      lysosome storage diseases.

PMID- 23878379
TI  - Ease of use, safety, and efficacy of integra bilayer wound matrix in the
      treatment of diabetic foot ulcers in an outpatient clinical setting: a
      prospective pilot study.
AB  - BACKGROUND: Integra bilayer wound matrix (IBWM) is a bilayer skin replacement
      system composed of a dermal regeneration layer and a temporary epidermal layer.
      It is used to treat various types of deep, large wounds via an inpatient
      procedure in an operating room. We sought to determine ease of use and
      effectiveness of IBWM in an outpatient clinical setting when treating diabetic
      foot ulcers. In addition, no epidermal autografting was performed in conjunction
      with the IBWM after silicone release, as is common in the inpatient setting.
      METHODS: This 12-week, single-arm, prospective pilot study was conducted in three
      outpatient clinics. Weekly evaluations included monitoring the wound for signs of
      infection during the 12-week follow-up phase. RESULTS: Eleven patients with
      diabetic foot ulcers who met the inclusion and exclusion criteria were enrolled.
      One patient was discontinued from the study owing to noncompliance leading to a
      serious adverse event. Therefore, ten patients who received the study
      intervention were included in the per-protocol population reported herein. The
      mean patient age was 60.6 years, with an average 11-year history of diabetes
      mellitus. Each ulcer was located on the plantar aspect of the foot. No infection
      was reported during the study. Patients treated with IBWM showed progressive
      wound healing over time: the greatest mean wound reduction was approximately 95%
      in week 12. Seven of ten patients (70%) achieved complete wound closure by week
      12. No recurrent ulcers were reported during follow-up. CONCLUSIONS: These
      results are consistent with the hypothesis that IBWM is easy to use, safe, and
      effective when used on diabetic foot ulcers in an outpatient clinical setting
      without the secondary procedure of autografting for closure.

PMID- 23878380
TI  - How effective is orthotic treatment in patients with recurrent diabetic foot
      ulcers?
AB  - BACKGROUND: We assessed the efficacy of customized foot orthotic therapy by
      comparing reulceration rates, minor amputation rates, and work and daily living
      activities before and after therapy. Peak plantar pressures and peak plantar
      impulses were compared with the patients not wearing and wearing their prescribed
      footwear. METHODS: One hundred seventeen patients with diabetes were prescribed
      therapeutic insoles and footwear based on the results of a detailed biomechanical
      study and were followed for 2 years. All of the patients had a history of foot
      ulcers, but none had undergone previous orthotic therapy. RESULTS: Before
      treatment, the reulceration rate was 79% and the amputation rate was 54%. Two
      years after the start of orthotic therapy, the reulceration rate was 15% and the
      amputation rate was 6%. Orthotic therapy reduced peak plantar pressures in
      patients with reulcerations and in those without (P < .05), although a
      significant decrease in peak plantar impulses was achieved only in patients not
      experiencing reulceration. Sick leave was reduced from 100% to 26%. CONCLUSIONS:
      Personalized orthotic therapy targeted at reducing plantar pressures by off
      loading protects high-risk patients against reulceration. Treatment reduced the
      reulceration rate and peak plantar pressures, leading to patients' return to work
      or other activities.

PMID- 23878381
TI  - Can Taekwondo footwear affect postural stability in young adults?
AB  - BACKGROUND: This study aims to investigate the effect of taekwondo footwear on
      unilateral stance stability and use of postural control strategies and to
      determine whether taekwondo footwear influences the somatosensory inputs for
      postural stability and postural strategies in young adults. METHODS: A quasi
      randomized crossover trial was conducted on 33 healthy young adults at a
      university research laboratory. Independent variables, including shoe conditions
      (shoes on and shoes off) and visual conditions (eyes open and eyes closed), were
      taken into account. The center of gravity (COG) sway velocity in unilateral
      stance and the strategy scores in the sensory organization test were measured. No
      intervention was given to the participants. RESULTS: There was no significant
      interaction between the two factors (the shoe and visual conditions) for COG sway
      velocities (P = .447) and strategy scores (P = .320). The shoe condition was not
      significant in either COG sway velocity (P = .484) or strategy score (P = .126).
      The visual condition was significant for COG sway velocity (P < .001) but not for
      strategy score (P = .573). The mean +/- SD COG sway velocity with eyes open was
      0.7 degrees  +/- 0.2 degrees /sec and with eyes closed was 1.7 degrees  +/- 0.6
      degrees /sec (P < .001). CONCLUSIONS: Taekwondo footwear is unlikely to affect
      somatosensory inputs and balance performance in young adults.

PMID- 23878382
TI  - Effect of shoe flexibility on plantar loading in children learning to walk.
AB  - BACKGROUND: In a previous pilot study of "cruisers" (nonindependent ambulation),
      "early walkers" (independent ambulation for 0-5 months), and "experienced
      walkers" (independent ambulation for 6-12 months), developmental age
      significantly affected the children's stability when walking and performing
      functional activities. We sought to examine how shoe structural characteristics
      affect plantar pressure distribution in early walkers. METHODS: Torsional
      flexibility was evaluated in four shoe designs (UltraFlex, MedFlex, LowFlex, and
      Stiff based on decreasing relative flexibility) with a structural testing
      machine. Plantar pressures were recorded in 25 early walkers while barefoot and
      shod at self-selected walking speeds. Peak pressure was calculated over ten
      masked regions for the barefoot and shod conditions. RESULTS: Torsional
      flexibility, the angular rotation divided by the applied moment about the long
      axis of the shoe, was different across the four shoe designs. As expected,
      UltraFlex was the most flexible and Stiff was the least flexible. As applied
      moment increased, torsional flexibility decreased in all footwear. When
      evaluating early walkers during gait, peak pressure was significantly different
      across shoe conditions for all of the masked regions. The stiffest shoe had the
      lowest peak pressures and the most flexible shoe had the highest. CONCLUSIONS: It
      is likely that increased shoe flexibility promoted greater plantar loading.
      Plantar pressures while wearing the most flexible shoe are similar to those while
      barefoot. This mechanical feedback may enhance proprioception, which is a
      desirable attribute for children learning to walk.

PMID- 23878383
TI  - Alterations in the plantar pressure patterns of overweight and obese
      schoolchildren due to backpack carriage.
AB  - BACKGROUND: Among other adverse consequences, childhood obesity is known to
      influence foot structure and functionality. Yet little information is available
      regarding how the physiologic foot-ground interaction is altered when a localized
      load is carried, as occurs in the case of schoolbags. We investigated plantar
      contact area and pressure modifications induced by backpack carriage under actual
      conditions. We hypothesized that a localized load acting on the body would
      further increase the already excessive plantar pressure that exists with
      overweight and obese status. METHODS: Seventy overweight and obese schoolchildren
      aged 6 to 11 years underwent two 30-sec trials on a pressure platform during a
      regular school day, with and without a backpack. Total and subregion contact
      areas along with peak plantar pressures were obtained, and results were compared
      with those of an equal-numbered group of normal-weight schoolchildren. RESULTS:
      Overweight and obese children generally had larger contact areas and higher peak
      plantar pressures compared with their normal-weight peers. In overweight and
      normal-weight participants, the backpack induced a similar generalized increase
      in contact area and pressures. However, the largest changes were observed in the
      forefoot, suggesting that load action tends to modify the physiologic pressure
      patterns. CONCLUSIONS: Backpack carriage raises the already elevated peak plantar
      pressures in overweight children during upright stance and modifies the
      physiologic pressure patterns. Further investigations are needed to clarify the
      features of such phenomenon when dynamic activities are performed and to verify
      the existence of fatigue and overexertion on the foot as well as other possible
      negative long-term effects.

PMID- 23878384
TI  - Anthropometric foot changes during pregnancy: a pilot study.
AB  - BACKGROUND: Women's feet change during pregnancy owing to hormonal and anatomical
      changes, thus having a strong influence on the decrease in their quality of life
      during pregnancy. This preliminary study aimed to value the anthropometric and
      positional changes that affect their feet. METHODS: Ten pregnant women were
      measured during their gestational period to analyze the anthropometric changes in
      their feet from the 12th week of pregnancy. We examined the changes that occured
      in foot length, forefoot width, arch of the foot height, and the fixed position
      of the foot by using the Foot Posture Index, and we analyzed three intervals
      corresponding to pregnancy weeks 12, 24, and 34. RESULTS: The most significant
      finding, with a reliability rate of 95%, is the decrease in internal arch height,
      which descends 0.65 mm (0.0394 inches) on average at the final stage of the
      pregnancy period. This change happened in 18 of the feet analyzed, tending toward
      pronation according to the measure provided by the Foot Posture Index, with a
      change of 3.78 points on this scale. CONCLUSIONS: The foot of the pregnant woman
      tends to flatten during gestational weeks 12 to 34, taking a more pronated
      posture, and the anthropometric changes in late pregnancy result in increases in
      foot length and forefoot width, changes that seem to be moderate.

PMID- 23878385
TI  - Plantar pressures, plantar forces, and their influence on the pathogenesis of
      diabetic foot ulcers: a review.
AB  - BACKGROUND: Clinical recommendations for the prevention and healing of diabetic
      foot ulcers (DFUs) are somewhat clear. However, assessment and quantification of
      the mechanical stress responsible for DFU remain complex. Different pressure
      variables have been described in the literature to better understand plantar
      tissue stress exposure. This article reviews the role of pressure and shear
      forces in the pathogenesis of plantar DFU. METHODS: We performed systematic
      searches of the PubMed and Embase databases, completed by a manual search of the
      selected studies. From 535 potentially relevant references, 70 studies were
      included in the full-text review. RESULTS: Variables of plantar mechanical stress
      relate to vertical pressure, shear stress, and temporality of loading. At this
      time, in-shoe peak plantar pressure (PPP) is the only reliable variable that can
      be used to prevent DFU. Although it is a poor predictor of in-shoe PPP, barefoot
      PPP seems complementary and may be more suitable when evaluating patients with
      diabetes mellitus and peripheral neuropathy who seem noncompliant with footwear.
      An in-shoe PPP threshold value of 200 kPa has been suggested to prevent DFU.
      Other variables, such as peak pressure gradient and peak maximal subsurface shear
      stress and its depth, seem to be of additional utility. CONCLUSIONS: To better
      assess the at-risk foot and to prevent ulceration, the practitioner should
      integrate quantitative models of dynamic foot plantar pressures, such as in-shoe
      and barefoot PPPs, with the regular clinical screening examination. Prospective
      studies are needed to evaluate causality between other variables of mechanical
      stress and DFUs.

PMID- 23878386
TI  - Malignant eccrine hidradenoma.
AB  - Hidradenomas are adenomatous tumors of sweat gland origin that are usually benign
      and can occur in any cutaneous skin surface. When malignant, the tumors have high
      recurrence rates and are often fatal. Because of their infrequency and clinical
      ambiguity, hidradenomas are often misdiagnosed as other soft-tissue masses.
      Radiation and chemotherapy have not shown to be of benefit; therefore, wide
      aggressive excision and lymphadenectomy are currently the treatments of choice.
      We present the case of a patient with a malignant hidradenoma presenting in her
      medial heel. After excisional biopsy identified the tumor, the patient was
      successfully treated with wide excision and delayed closure via vacuum-assisted
      closure. 

PMID- 23878387
TI  - Stress fracture of the lateral cuneiform bone: a case report.
AB  - Stress fractures are common overuse injuries of the bone that are most often seen
      in athletes and military personnel. These types of injuries seem to be commonly
      missed or delayed in diagnosis. Physicians should consider the possibility of
      such an injury while determining the diagnosis of a long-lasting foot pain. The
      aim of this paper was to report an isolated stress fracture of the lateral
      cuneiform bone. A review of the literature failed to find a similar case. 

PMID- 23878388
TI  - Metastatic bone cancer of the foot: a case report.
AB  - Metastasis to the foot is rarely presented in the literature. We describe a 56
      year-old woman with nonspecific pain in the left foot, ankle, and knee for 3
      months. The patient was diagnosed as having urothelial carcinoma with metastasis
      to the left lower extremity, including the foot. This diagnosis was reached
      through the combined efforts of radiologic techniques and biopsies. This case
      discusses the importance of paying close attention to the details of the history
      and physical examination, performing appropriate tests, and obtaining suitable
      referrals. 

PMID- 23878389
TI  - Does prevention always equal remission in diabetic foot care? more than
      semantics.

PMID- 23878390
TI  - MicroRNA 329 suppresses angiogenesis by targeting CD146.
AB  - CD146, an endothelial biomarker, has been shown to be aberrantly upregulated
      during pathological angiogenesis and functions as a coreceptor for vascular
      endothelial growth factor receptor 2 (VEGFR-2) to promote disease progression.
      However, the regulatory mechanisms of CD146 expression during angiogenesis remain
      unclear. Using a microRNA screening approach, we identified a novel negative
      regulator of angiogenesis, microRNA 329 (miR-329), that directly targeted CD146
      and inhibited CD146-mediated angiogenesis in vitro and in vivo. Endogenous miR
      329 expression was downregulated by VEGF and tumor necrosis factor alpha (TNF
      alpha), resulting in the elevation of CD146 in endothelial cells. Upregulation of
      CD146 facilitated an endothelial response to VEGF-induced SRC kinase family
      (SKF)/p38 mitogen-activated protein kinase (MAPK)/NF-kappaB activation and
      consequently promoted endothelial cell migration and tube formation. Our animal
      experiments showed that treatment with miR-329 repressed excessive CD146
      expression on blood vessels and significantly attenuated neovascularization in a
      mouse model of pathological angiogenesis. Our findings provide the first evidence
      that CD146 expression in angiogenesis is regulated by miR-329 and suggest that
      miR-329 could present a potential therapeutic tool for the treatment of
      angiogenic diseases. 

PMID- 23878391
TI  - Brain-derived neurotrophic factor signaling rewrites the glucocorticoid
      transcriptome via glucocorticoid receptor phosphorylation.
AB  - Abnormal glucocorticoid and neurotrophin signaling has been implicated in
      numerous psychiatric disorders. However, the impact of neurotrophic signaling on
      glucocorticoid receptor (GR)-dependent gene expression is not understood. We
      therefore examined the impact of brain-derived neurotrophic factor (BDNF)
      signaling on GR transcriptional regulatory function by gene expression profiling
      in primary rat cortical neurons stimulated with the selective GR agonist
      dexamethasone (Dex) and BDNF, alone or in combination. Simultaneous treatment
      with BDNF and Dex elicited a unique set of GR-responsive genes associated with
      neuronal growth and differentiation and also enhanced the induction of a large
      number of Dex-sensitive genes. BDNF via its receptor TrkB enhanced the
      transcriptional activity of a synthetic GR reporter, suggesting a direct effect
      of BDNF signaling on GR function. Indeed, BDNF treatment induces the
      phosphorylation of GR at serine 155 (S155) and serine 287 (S287). Expression of a
      nonphosphorylatable mutant (GR S155A/S287A) impaired the induction of a subset of
      BDNF- and Dex-regulated genes. Mechanistically, BDNF-induced GR phosphorylation
      increased GR occupancy and cofactor recruitment at the promoter of a BDNF
      enhanced gene. GR phosphorylation in vivo is sensitive to changes in the levels
      of BDNF and TrkB as well as stress. Therefore, BDNF signaling specifies and
      amplifies the GR transcriptome through a coordinated GR phosphorylation-dependent
      detection mechanism. 

PMID- 23878392
TI  - Mechanisms of STIM1 activation of store-independent leukotriene C4-regulated Ca2+
      channels.
AB  - We recently showed, in primary vascular smooth muscle cells (VSMCs), that the
      platelet-derived growth factor activates canonical store-operated Ca(2+) entry
      and Ca(2+) release-activated Ca(2+) currents encoded by Orai1 and STIM1 genes.
      However, thrombin activates store-independent Ca(2+) selective channels
      contributed by both Orai3 and Orai1. These store-independent Orai3/Orai1 channels
      are gated by cytosolic leukotriene C4 (LTC4) and require STIM1 downstream LTC4
      action. However, the source of LTC4 and the signaling mechanisms of STIM1 in the
      activation of this LTC4-regulated Ca(2+) (LRC) channel are unknown. Here, we show
      that upon thrombin stimulation, LTC4 is produced through the sequential
      activities of phospholipase C, diacylglycerol lipase, 5-lipo-oxygenease, and
      leukotriene C4 synthase. We show that the endoplasmic reticulum-resident STIM1 is
      necessary and sufficient for LRC channel activation by thrombin. STIM1 does not
      form sustained puncta and does not colocalize with Orai1 either under basal
      conditions or in response to thrombin. However, STIM1 is precoupled to Orai3 and
      Orai3/Orai1 channels under basal conditions as shown using Forster resonance
      energy transfer (FRET) imaging. The second coiled-coil domain of STIM1 is
      required for coupling to either Orai3 or Orai3/Orai1 channels and for LRC channel
      activation. We conclude that STIM1 employs distinct mechanisms in the activation
      of store-dependent and store-independent Ca(2+) entry pathways. 

PMID- 23878393
TI  - Role of membrane association and Atg14-dependent phosphorylation in beclin-1
      mediated autophagy.
AB  - During autophagy, a double membrane envelops cellular material for trafficking to
      the lysosome. Human beclin-1 and its yeast homologue, Atg6/Vps30, are scaffold
      proteins bound in a lipid kinase complex with multiple cellular functions,
      including autophagy. Several different Atg6 complexes exist, with an autophagy
      specific form containing Atg14. However, the roles of Atg14 and beclin-1 in the
      activation of this complex remain unclear. We here addressed the mechanism of
      beclin-1 complex activation and reveal two critical steps in this pathway. First,
      we identified a unique domain in beclin-1, conserved in the yeast homologue Atg6,
      which is involved in membrane association and, unexpectedly, controls
      autophagosome size and number in yeast. Second, we demonstrated that human Atg14
      is critical in controlling an autophagy-dependent phosphorylation of beclin-1. We
      map these novel phosphorylation sites to serines 90 and 93 and demonstrate that
      phosphorylation at these sites is necessary for maximal autophagy. These results
      help clarify the mechanism of beclin-1 and Atg14 during autophagy. 

PMID- 23878394
TI  - Phosphorylation regulates FOXC2-mediated transcription in lymphatic endothelial
      cells.
AB  - One of the key mechanisms linking cell signaling and control of gene expression
      is reversible phosphorylation of transcription factors. FOXC2 is a forkhead
      transcription factor that is mutated in the human vascular disease lymphedema
      distichiasis and plays an essential role in lymphatic vascular development.
      However, the mechanisms regulating FOXC2 transcriptional activity are not well
      understood. We report here that FOXC2 is phosphorylated on eight evolutionarily
      conserved proline-directed serine/threonine residues. Loss of phosphorylation at
      these sites triggers substantial changes in the FOXC2 transcriptional program.
      Through genome-wide location analysis in lymphatic endothelial cells, we
      demonstrate that the changes are due to selective inhibition of FOXC2 recruitment
      to chromatin. The extent of the inhibition varied between individual binding
      sites, suggesting a novel rheostat-like mechanism by which expression of specific
      genes can be differentially regulated by FOXC2 phosphorylation. Furthermore,
      unlike the wild-type protein, the phosphorylation-deficient mutant of FOXC2
      failed to induce vascular remodeling in vivo. Collectively, our results point to
      the pivotal role of phosphorylation in the regulation of FOXC2-mediated
      transcription in lymphatic endothelial cells and underscore the importance of
      FOXC2 phosphorylation in vascular development. 

PMID- 23878395
TI  - Induction of p38delta expression plays an essential role in oncogenic ras-induced
      senescence.
AB  - Oncogene-induced senescence is a stable proliferative arrest that serves as a
      tumor-suppressing defense mechanism. p38 mitogen-activated protein kinase (MAPK)
      has been implicated in oncogene-induced senescence and tumor suppression.
      However, the specific role of each of the four p38 isoforms in oncogene-induced
      senescence is not fully understood. Here, we demonstrate that p38delta mediates
      oncogene-induced senescence through a p53- and p16(INK4A)-independent mechanism.
      Instead, evidence suggests a link between p38delta and the DNA damage pathways.
      Moreover, we have discovered a novel mechanism that enhances the expression of
      p38delta during senescence. In this mechanism, oncogenic ras induces the Raf-1
      MEK-extracellular signal-regulated kinase (ERK) pathway, which, in turn,
      activates the AP-1 and Ets transcription factors that are bound to the p38delta
      promoter, leading to increased transcription of p38delta. These findings indicate
      that induction of the prosenescent function of p38delta by oncogenic ras is
      achieved through 2 mechanisms, transcriptional activation by the Raf-1-MEK-ERK-AP
      1/Ets pathway, which increases the cellular concentration of the p38delta
      protein, and posttranslational modification by MKK3/6, which stimulates the
      enzymatic activity of p38delta. In addition, these studies identify the AP-1 and
      Ets transcription factors as novel signaling components in the senescence
      inducing pathway. 

PMID- 23878396
TI  - The yeast Snt2 protein coordinates the transcriptional response to hydrogen
      peroxide-mediated oxidative stress.
AB  - Regulation of gene expression is a vital part of the cellular stress response,
      yet the full set of proteins that orchestrate this regulation remains unknown.
      Snt2 is a Saccharomyces cerevisiae protein whose function has not been well
      characterized that was recently shown to associate with Ecm5 and the Rpd3
      deacetylase. Here, we confirm that Snt2, Ecm5, and Rpd3 physically associate. We
      then demonstrate that cells lacking Rpd3 or Snt2 are resistant to hydrogen
      peroxide (H2O2)-mediated oxidative stress and use chromatin immunoprecipitation
      followed by high-throughput sequencing (ChIP-seq) to show that Snt2 and Ecm5
      recruit Rpd3 to a small number of promoters and in response to H2O2, colocalize
      independently of Rpd3 to the promoters of stress response genes. By integrating
      ChIP-seq and expression analyses, we identify target genes that require Snt2 for
      proper expression after H2O2. Finally, we show that cells lacking Snt2 are also
      resistant to nutrient stress imparted by the TOR (target of rapamycin) pathway
      inhibitor rapamycin and identify a common set of genes targeted by Snt2 and Ecm5
      in response to both H2O2 and rapamycin. Our results establish a function for Snt2
      in regulating transcription in response to oxidative stress and suggest Snt2 may
      also function in multiple stress pathways. 

PMID- 23878397
TI  - Platelet-derived growth factor/vascular endothelial growth factor receptor
      inactivation by sunitinib results in Tsc1/Tsc2-dependent inhibition of TORC1.
AB  - Vascular endothelial growth factor (VEGF) and platelet-derived growth factor
      (PDGF) receptors are implicated in development and tumorigenesis and dual
      inhibitors like sunitinib are prescribed for cancer treatment. While mammalian
      VEGF and PDGF receptors are present in multiple isoforms and heterodimers,
      Drosophila encodes one ancestral PDGF/VEGF receptor, PVR. We identified PVR in an
      unbiased cell-based RNA interference (RNAi) screen of all Drosophila kinases and
      phosphatases for novel regulators of TORC1. PVR is essential to sustain target of
      rapamycin complex 1 (TORC1) and extracellular signal-regulated kinase (ERK)
      activity in cultured insect cells and for maximal stimulation by insulin. CG32406
      (henceforth, PVRAP, for PVR adaptor protein), an Src homology 2 (SH2) domain
      containing protein, binds PVR and is required for TORC1 activation. TORC1
      activation by PVR involves Tsc1/Tsc2 and, in a cell-type-dependent manner, Lobe
      (ortholog of PRAS40). PVR is required for cell survival in vitro, and both PVR
      and TORC1 are necessary for hemocyte expansion in vivo. Constitutive PVR
      activation induces tumor-like structures that exhibit high TORC1 activity. Like
      its mammalian orthologs, PVR is inhibited by sunitinib, and sunitinib treatment
      phenocopies PVR loss in hemocytes. Sunitinib inhibits TORC1 in insect cells, and
      sunitinib-mediated TORC1 inhibition requires an intact Tsc1/Tsc2 complex.
      Sunitinib similarly inhibited TORC1 in human endothelial cells in a Tsc1/Tsc2
      dependent manner. Our findings provide insight into the mechanism of action of
      PVR and may have implications for understanding sunitinib sensitivity and
      resistance in tumors. 

PMID- 23878398
TI  - Cap completion and C-terminal repeat domain kinase recruitment underlie the
      initiation-elongation transition of RNA polymerase II.
AB  - After transcription initiation, RNA polymerase (Pol) II escapes from the promoter
      and recruits elongation factors. The molecular basis for the initiation
      elongation factor exchange during this transition remains poorly understood.
      Here, we used chromatin immunoprecipitation (ChIP) to elucidate the initiation
      elongation transition of Pol II in the budding yeast Saccharomyces cerevisiae. We
      show that the early Pol II elongation factor Spt5 contributes to stable
      recruitment of the mRNA capping enzymes Cet1, Ceg1, and Abd1. Genome-wide
      occupancy for Cet1 and Ceg1 is restricted to the transcription start site (TSS),
      whereas occupancy for Abd1 peaks at ~110 nucleotides downstream, and occupancy
      for the cap-binding complex (CBC) rises subsequently. Abd1 and CBC are important
      for recruitment of the kinases Ctk1 and Bur1, which promote elongation and
      capping enzyme release. These results suggest that cap completion stimulates
      productive Pol II elongation.

PMID- 23878399
TI  - Id2 complexes with the SNAG domain of Snai1 inhibiting Snai1-mediated repression
      of integrin beta4.
AB  - The epithelial-mesenchymal transition (EMT) is a fundamental process that
      underlies development and cancer. Although the EMT involves alterations in the
      expression of specific integrins that mediate stable adhesion to the basement
      membrane, such as alpha6beta4, the mechanisms involved are poorly understood.
      Here, we report that Snai1 inhibits beta4 transcription by increasing repressive
      histone modification (trimethylation of histone H3 at K27 [H3K27Me3]).
      Surprisingly, Snai1 is expressed and localized in the nucleus in epithelial
      cells, but it does not repress beta4. We resolved this paradox by discovering
      that Id2 complexes with the SNAG domain of Snai1 on the beta4 promoter and
      constrains the repressive function of Snai1. Disruption of the complex by
      depleting Id2 resulted in Snai1-mediated beta4 repression with a concomitant
      increase in H3K27Me3 modification on the beta4 promoter. These findings establish
      a novel function for Id2 in regulating Snai1 that has significant implications
      for the regulation of epithelial gene expression. 

PMID- 23878400
TI  - The human RVB complex is required for efficient transcription of type I
      interferon-stimulated genes.
AB  - Type I interferons (IFNs) stimulate transcription through a latent heterotrimeric
      transcription factor composed of tyrosine-phosphorylated STAT1 and STAT2 and the
      DNA binding partner IRF9, with STAT2 contributing a critical transactivation
      domain. Human RVB1 and RVB2, which are highly conserved AAA(+) ATP binding
      proteins contained in chromatin-remodeling complexes such as Ino80, SNF2-related
      CBP activator protein (SRCAP), and Tip60/NuA4, interacted with the
      transactivation domain of STAT2 in the nuclei of IFN-stimulated cells. RNA
      interference (RNAi) experiments demonstrated that RVB proteins were required for
      robust activation of IFN-alpha-stimulated genes (ISGs). The requirement for RVB
      proteins was specific to IFN-alpha/STAT2 signaling; transcription of tumor
      necrosis factor alpha (TNF-alpha)- and IFN-gamma-driven genes was not affected by
      RVB1 depletion. Using RNAi-based depletion, we assessed the involvement of
      catalytic subunits of the RVB-containing Tip60, BRD8, Ino80, SRCAP, and URI
      complexes. No component other than RVB1/2 was uniquely required for ISG
      induction, suggesting that RVB1/2 functions as part of an as yet unidentified
      complex. Chromatin immunoprecipitation assays indicated that RVB1/2 was required
      for recruitment of RNA polymerase II (Pol II) to ISG promoters but was
      dispensable for STAT2 recruitment to chromatin. We hypothesize that an RVB1/2
      chromatin-remodeling complex is required for efficient Pol II recruitment and
      initiation at ISG promoters and is recruited through interaction with the STAT2
      transactivation domain. 

PMID- 23878401
TI  - Investigations on aberrant glycosylation of glycosphingolipids in colorectal
      cancer tissues using liquid chromatography and matrix-assisted laser desorption
      time-of-flight mass spectrometry (MALDI-TOF-MS).
AB  - Cancer is a leading cause of death and alterations of glycosylation are
      characteristic features of malignant cells. Colorectal cancer is one of the most
      common cancers and its exact causes and biology are not yet well understood.
      Here, we compared glycosylation profiles of colorectal tumor tissues and
      corresponding control tissues of 13 colorectal cancer patients to contribute to
      the understanding of this cancer. Using MALDI-TOF(/TOF)-MS and 2-dimensional LC
      MS/MS we characterized enzymatically released and 2-aminobenzoic acid labeled
      glycans from glycosphingolipids. Multivariate data analysis revealed significant
      differences between tumor and corresponding control tissues. Main discriminators
      were obtained, which represent the overall alteration in glycosylation of
      glycosphingolipids during colorectal cancer progression, and these were found to
      be characterized by (1) increased fucosylation, (2) decreased acetylation, (3)
      decreased sulfation, (4) reduced expression of globo-type glycans, as well as (5)
      disialyl gangliosides. The findings of our current research confirm former
      reports, and in addition expand the knowledge of glycosphingolipid glycosylation
      in colorectal cancer by revealing new glycans with discriminative power and
      characteristic, cancer-associated glycosylation alterations. The obtained
      discriminating glycans can contribute to progress the discovery of biomarkers to
      improve diagnostics and patient treatment. 

PMID- 23878402
TI  - Rapid and deep human proteome analysis by single-dimension shotgun proteomics.
AB  - Multiparameter optimization of an LC-MS/MS shotgun proteomics experiment was
      performed without any hardware or software modification of the commercial
      instrument. Under the optimized experimental conditions, with a 50-cm-long
      separation column and a 4-h LC-MS run (including a 3-h optimized gradient), 4,825
      protein groups and 37,550 peptides were identified in a single run and 5,354
      protein groups and 56,390 peptides in a triplicate analysis of the A375 human
      cell line, for approximately 50% coverage of the expressed proteome. The major
      steps enabling such performance included optimization of the cell lysis and
      protein extraction, digestion of even insoluble cell debris, tailoring the LC
      gradient profile, and choosing the optimal dynamic exclusion window in data
      dependent MS/MS, as well as the optimal m/z scan window. 

PMID- 23878403
TI  - Tsunami-tendenko and morality in disasters.

PMID- 23878404
TI  - Pre-emptive suicide, precedent autonomy and preclinical Alzheimer disease.

PMID- 23878405
TI  - Measuring Maternal Nonstandard Work in Survey Data.
AB  - Surveys differ in the measurement of nonstandard work, such that some surveys
      require respondents to indicate whether they work either a standard or a
      nonstandard schedule, whereas others allow respondents to indicate that they work
      both types of schedules. We test whether these measurement decisions influence
      the estimated prevalence of maternal nonstandard work, using data from two
      sources: the Current Population Survey (N = 1,430) and the Fragile Families and
      Child Wellbeing Study (N = 2,524). Using propensity score techniques, we find
      that giving respondents the option of reporting work at more than one type of
      schedule doubles the prevalence of nonstandard work, compared to allowing
      respondents to indicate only one type of schedule. Our results suggest that many
      mothers of young children regularly work at both standard and nonstandard times
      and that mutually exclusive conceptualizations of standard and nonstandard work
      schedules do not fully capture their experiences.

PMID- 23878406
TI  - GRGDS-Functionalized Poly(lactide)-graft-poly(ethylene glycol) Copolymers:
      Combining Thiol-Ene Chemistry with Staudinger Ligation.
AB  - A tri(ethylene glycol)-containing lactide analogue was synthesized via thiol-ene
      chemistry between a bi-functional triethylene glycol and allyl lactide.
      Subsequent tin-octoate-catalyzed ring-opening polymerization yielded well-defined
      poly(lactide)-graft-poly(ethylene glycol) copolymers with molecular weights of
      6000 g/mol and polydispersity indices of 1.6. The tri(ethylene glycol) chains
      along the copolymers contain azide termini that are capable of 'click'-type
      postpolymerization functionalization. The utility of this strategy was
      demonstrated via successful Staudinger ligation to install the Gly-Arg-Gly-Asp
      Ser (GRGDS) peptide.

PMID- 23878407
TI  - Analysis of High-Dimensional Structure-Activity Screening Datasets Using the
      Optimal Bit String Tree.
AB  - A new classification method called the Optimal Bit String Tree is proposed to
      identify quantitative structure-activity relationships (QSARs). The method
      introduces the concept of a chromosome to describe the presence/absence context
      of a combination of descriptors. A descriptor set and its optimal chromosome form
      the splitting variable. A new stochastic searching scheme that contains a
      weighted sampling scheme, simulated annealing, and a trimming procedure optimizes
      the choice of splitting variable. Simulation studies and an application to
      screening monoamine oxidase (MAO) inhibitors show that OBSTree is advantageous in
      accurately and effectively identifying QSAR rules and finding different classes
      of active compounds. Details of the algorithm, SAS code, and simulated and real
      datasets are available online as supplementary materials.

PMID- 23878408
TI  - Total syntheses of the squalene-derived halogenated polyethers ent
      dioxepandehydrothyrsiferol and armatol A via bromonium- and Lewis acid-initiated
      epoxide-opening cascades.
AB  - Herein we describe in full our investigations leading to the first total
      syntheses of ent-dioxepandehydrothyrsiferol and armatol A. Discovery of a
      bromonium-initiated epoxide-opening cascade enabled novel tactics for
      constructing key fragments found in both natural products and have led us to
      revise the proposed biogeneses. Other common features found in the routes include
      convergent fragment coupling strategies to assemble the natural products'
      backbones and the use of epoxide-opening cascades for rapid constructions of the
      fused polyether subunits. Through de novo synthesis of armatol A, we elucidate
      the absolute and relative configuration of this natural product.

PMID- 23878409
TI  - BUILDING A RESEARCH-COMMUNITY COLLABORATIVE TO IMPROVE COMMUNITY CARE FOR INFANTS
      AND TODDLERS AT-RISK FOR AUTISM SPECTRUM DISORDERS.
AB  - This article describes the formation and initial outcomes of a research-community
      collaborative group that was developed based on community-based participatory
      research principles. The group includes a transdisciplinary team of
      practitioners, funding agency representatives, researchers, and families of
      children with autism spectrum disorders, who partnered to improve community-based
      care for infants and toddlers at risk for autism through the implementation of
      evidence-based practices. Data from this group provide support for the
      feasibility of developing and sustaining a highly synergistic and productive
      research-community collaborative group who shares common goals to improve
      community care.

PMID- 23878410
TI  - Conceptualizing the Step-Down for Foster Youth Approaching Adulthood: Perceptions
      of Service Providers, Caseworkers, and Foster Parents.
AB  - Studies find considerable movement between residential treatment and less
      restrictive foster home settings, with approximately half of foster youth who are
      stepped down eventually returning to a higher level of care. Very little is known
      about the step down for foster youth who are approaching adulthood in locked
      residential facilities. A qualitative study of stepping down a small sample of
      foster youth, as perceived by team members delivering a model of treatment foster
      care, is presented. These findings reveal the dimensions of stepping down foster
      youth at the onset of adulthood, and highlight the importance of providing foster
      youth with developmental opportunities to engage in the social roles and tasks of
      late adolescence and/or early adulthood. Implications for further refining the
      concept of stepping down from a developmental perspective are discussed.

PMID- 23878411
TI  - Sulfide Oxidation by O2: Synthesis, Structure and Reactivity of Novel Sulfide
      Incorporated Fe(II) Bis(imino)pyridine Complexes.
AB  - The unsymmetrical iron(II) bis(imino)pyridine complexes
      [FeII(LN3SMe)(H2O)3](OTf)2 (1), and [FeII(LN3SMe)Cl2] (2) were synthesized and
      their reactivity with O2 was examined. Complexes 1 and 2 were characterized by
      single crystal X-ray crystallography, LDI-MS, 1H-NMR and elemental analysis. The
      LN3SMe ligand was designed to incorporate a single sulfide donor and relies on
      the bis(imino)pyridine scaffold. This scaffold was selected for its ease of
      synthesis and its well-precedented ability to stabilize Fe(II) ions. Complexes 1
      and 2 ware prepared via a metal-assisted template reaction from the unsymmetrical
      pyridyl ketone precursor 2-(O=CMe)-6-(2,6-(iPr2-C6H3N=CMe)-C5H3N. Reaction of 1
      with O2 was shown to afford the S-oxygenated sulfoxide complex
      [Fe(LN3S(O)Me)(OTf)]2+(3), whereas compound 2, under the same reaction
      conditions, afforded the corresponding sulfone complex [Fe(LN3S(O2)Me)Cl]2+ (4).

PMID- 23878412
TI  - Random errors in egocentric networks.
AB  - The systematic errors that are induced by a combination of human memory
      limitations and common survey design and implementation have long been studied in
      the context of egocentric networks. Despite this, little if any work exists in
      the area of random error analysis on these same networks; this paper offers a
      perspective on the effects of random errors on egonet analysis, as well as the
      effects of using egonet measures as independent predictors in linear models. We
      explore the effects of false-positive and false-negative error in egocentric
      networks on both standard network measures and on linear models through
      simulation analysis on a ground truth egocentric network sample based on facebook
      friendships. Results show that 5-20% error rates, which are consistent with error
      rates known to occur in ego network data, can cause serious misestimation of
      network properties and regression parameters.

PMID- 23878413
TI  - Individual Differences in Numeracy and Cognitive Reflection, with Implications
      for Biases and Fallacies in Probability Judgment.
AB  - Despite evidence that individual differences in numeracy affect judgment and
      decision making, the precise mechanisms underlying how such differences produce
      biases and fallacies remain unclear. Numeracy scales have been developed without
      sufficient theoretical grounding, and their relation to other cognitive tasks
      that assess numerical reasoning, such as the Cognitive Reflection Test (CRT), has
      been debated. In studies conducted in Brazil and in the USA, we administered an
      objective Numeracy Scale (NS), Subjective Numeracy Scale (SNS), and the CRT to
      assess whether they measured similar constructs. The Rational-Experiential
      Inventory, inhibition (go/no-go task), and intelligence were also investigated.
      By examining factor solutions along with frequent errors for questions that
      loaded on each factor, we characterized different types of processing captured by
      different items on these scales. We also tested the predictive power of these
      factors to account for biases and fallacies in probability judgments. In the
      first study, 259 Brazilian undergraduates were tested on the conjunction and
      disjunction fallacies. In the second study, 190 American undergraduates responded
      to a ratio-bias task. Across the different samples, the results were remarkably
      similar. The results indicated that the CRT is not just another numeracy scale,
      that objective and subjective numeracy scales do not measure an identical
      construct, and that different aspects of numeracy predict different biases and
      fallacies. Dimensions of numeracy included computational skills such as
      multiplying, proportional reasoning, mindless or verbatim matching, metacognitive
      monitoring, and understanding the gist of relative magnitude, consistent with
      dual-process theories such as fuzzy-trace theory.

PMID- 23878414
TI  - Do polymorphisms in chemosensory genes matter for human ingestive behavior?
AB  - In the last decade, basic research in chemoreceptor genetics and neurobiology
      have revolutionized our understanding of individual differences in
      chemosensation. From an evolutionary perspective, chemosensory variations appear
      to have arisen in response to different living environments, generally in the
      avoidance of toxins and to better detect vital food sources. Today, it is often
      assumed that these differences may drive variable food preferences and choices,
      with downstream effects on health and wellness. A growing body of evidence
      indicates chemosensory variation is far more complex than previously believed.
      However, just because a genetic polymorphism results in altered receptor function
      in cultured cells or even behavioral phenotypes in the laboratory, this variation
      may not be sufficient to influence food choice in free living humans. Still,
      there is ample evidence to indicate allelic variation in TAS2R38 predicts
      variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and
      natural plant compounds (e.g., goitrin), and this variation associates with
      differential intake of alcohol and vegetables. Further, this is only one of 25
      unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests
      other TAS2Rs may also contain polymorphisms that a functional with respect to
      ingestive behavior. For example, TAS2R16 polymorphisms are linked to the
      bitterness of naturally occurring plant compounds and alcoholic beverage intake,
      a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit
      bitterness and liking, and TAS2R31 polymorphisms associate with differential
      bitterness of plant compounds like aristolochic acid and the sulfonyl amide
      sweeteners saccharin and acesulfame-K. More critically with respect to food
      choices, these polymorphisms may vary independently from each other within and
      across individuals, meaning a monolithic one-size-fits-all approach to bitterness
      needs to be abandoned. Nor are genetic differences restricted to bitterness.
      Perceptual variation has also been associated with polymorphisms in genes
      involved in odors associated with meat defects (boar taint), green/grassy notes,
      and cilantro, as well as umami and sweet tastes (TAS1R1/2/3). Here, a short
      primer on receptor genetics is provided, followed by a summary of current
      knowledge, and implications for human ingestive behavior are discussed.

PMID- 23878416
TI  - Vaccines, Social Mobilization, or any Other Game changer: Polio Eradication is an
      Unfinished Narrative.

PMID- 23878415
TI  - Activation of TRPV1 prevents OxLDL-induced lipid accumulation and TNF-alpha
      induced inflammation in macrophages: role of liver X receptor alpha.
AB  - The transient receptor potential vanilloid type 1 (TRPV1) is crucial in the
      pathogenesis of atherosclerosis; yet its role and underlying mechanism in the
      formation of macrophage foam cells remain unclear. Here, we show increased TRPV1
      expression in the area of foamy macrophages in atherosclerotic aortas of
      apolipoprotein E-deficient mice. Exposure of mouse bone-marrow-derived
      macrophages to oxidized low-density lipoprotein (oxLDL) upregulated the
      expression of TRPV1. In addition, oxLDL activated TRPV1 and elicited calcium
      (Ca(2+)) influx, which were abrogated by the pharmacological TRPV1 antagonist
      capsazepine. Furthermore, oxLDL-induced lipid accumulation in macrophages was
      ameliorated by TRPV1 agonists but exacerbated by TRPV1 antagonist. Treatment with
      TRPV1 agonists did not affect the internalization of oxLDL but promoted
      cholesterol efflux by upregulating the efflux ATP-binding cassette (ABC)
      transporters ABCA1 and ABCG1. Moreover, the upregulation of ABC transporters was
      mainly through liver X receptor alpha-(LXRalpha-) dependent regulation of
      transcription. Moreover, the TNF-alpha-induced inflammatory response was
      alleviated by TRPV1 agonists but aggravated by the TRPV1 antagonist and LXR alpha
      siRNA in macrophages. Our data suggest that LXR alpha plays a pivotal role in
      TRPV1-activation-conferred protection against oxLDL-induced lipid accumulation
      and TNF-alpha-induced inflammation in macrophages.

PMID- 23878417
TI  - Universal health coverage for India by 2022: a utopia or reality?
AB  - It is the obligation of the state to provide free and universal access to quality
      health-care services to its citizens. India continues to be among the countries
      of the world that have a high burden of diseases. The various health program and
      policies in the past have not been able to achieve the desired goals and
      objectives. 65(th) World Health Assembly in Geneva identified universal health
      coverage (UHC) as the key imperative for all countries to consolidate the public
      health advances. Accordingly, Planning Commission of India constituted a high
      level expert group (HLEG) on UHC in October 2010. HLEG submitted its report in
      Nov 2011 to Planning Commission on UHC for India by 2022. The recommendations for
      the provision of UHC pertain to the critical areas such as health financing,
      health infrastructure, health services norms, skilled human resources, access to
      medicines and vaccines, management and institutional reforms, and community
      participation. India faces enormous challenges to achieve UHC by 2022 such as
      high disease prevalence, issues of gender equality, unregulated and fragmented
      health-care delivery system, non-availability of adequate skilled human resource,
      vast social determinants of health, inadequate finances, lack of inter-sectoral
      co-ordination and various political pull and push of different forces, and
      interests. These challenges can be met by a paradigm shift in health policies and
      programs in favor of vulnerable population groups, restructuring of public health
      cadres, reorientation of undergraduate medical education, more emphasis on public
      health research, and extensive education campaigns. There are still areas of
      concern in fulfilling the objectives of achieving UHC by 2022 regarding financing
      model for health-care delivery, entitlement package, cost of health-care
      interventions and declining state budgets. However, the Government's commitment
      to provide adequate finances, recent bold social policy initiatives and
      enactments such as food security bill, enhanced participation by civil society in
      all health matters, major initiative by some states such as Tamil Nadu to improve
      health, water, and sanitation services are good enough reasons for hope that UHC
      can be achieved by 2022. However, in the absence of sustained financial support,
      strong political will and leadership, dedicated involvement of all stakeholders
      and community participation, attainment of UHC by 2022 will remain a Utopia. 

PMID- 23878418
TI  - Adherence to antiretroviral therapy in India: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To assess the adherence to antiretroviral therapy (ART) in the human
      immunodeficiency virus (HIV)-infected population in India. DESIGN: Systematic
      review and meta-analysis. MATERIALS AND METHODS: The Medline and Cochrane library
      database were searched. Any prospective or retrospective study enrolling a
      minimum of 10 subjects with a primary objective of assessing ART adherence in the
      HIV population in India was included. Data were extracted on adherence
      definition, adherence estimates, study design, study population characteristics,
      recall period and assessment method. For metaanalysis, the pooled proportion was
      calculated as a back-transform of the weighted mean of the transformed
      proportions (calculated according to the Freeman-Tukey variant of the arcsine
      square root) using the random effects model. RESULTS: There were seven cross
      sectional studies and one retrospective study enrolling 1666 participants.
      Publication bias was significant (P = 0.003). Pooled results showed an ART
      adherence rate of 70% (95% confidence interval: 59-81%, I(2) = 96.3%).
      Sensitivity analyses based on study design, adherence assessment method and study
      region did not influence adherence estimates. Fifty percent (4/8) of the studies
      reported cost of medication as the most common obstacle for ART adherence. Twenty
      five percent (2/8) reported lack of access to medication as the reason for non
      adherence and 12% (1/8) cited adverse events as the most prevalent reason for non
      adherence. The overall methodological quality of the included studies was poor.
      CONCLUSION: Pooled results show that overall ART adherence in India is below the
      required levels to have an optimal treatment effect. The quality of studies is
      poor and cannot be used to guide policies to improve ART adherence.

PMID- 23878419
TI  - Is myopia a public health problem in India?
AB  - Myopia, a form of refractive error is a leading cause of visual disability
      throughout the world. In India uncorrected refractive errors are the most common
      cause of visual impairment and second major cause of avoidable blindness. Due to
      this the public health and economic impact of myopia is enormous. Although school
      vision screening programme is very successful in many states, still a significant
      number of school going children remain unidentified and the unmet need for
      correcting refractive errors in children appears to be significant. 

PMID- 23878420
TI  - Hepatitis C Virus Infection in HIV Positive Attendees of Shiraz Behavioral
      Diseases Consultation Center in Southern Iran.
AB  - OBJECTIVE: To determine the prevalence of HCV co-infection and its correlation
      with demographic and risk factors among human immunodeficiency virus (HIV)
      infected individuals attending Shiraz behavioral diseases consultation (SBDC)
      Center in southern Iran. MATERIALS AND METHODS: In a cross-sectional study, 226
      consecutive HIV-positive patients who referred to SBDC Center from April 2006 to
      March 2007 were interviewed face-to-face to record demographic data and risk
      factors of HIV transmission. A 10ml sample of venous blood was drawn from every
      subject and tested for HCV-antibodies by third generation enzyme linked
      immunosorbant (ELISA) and recombinant immunoblot assays (RIBA). All samples were
      also analyzed by qualitative reverse transcriptase polymerase chain reaction (RT
      PCR) for detection of HCV-RNA. RESULTS: The study population consisted of 214 men
      (94.7%) and 12 women (5.3%) with a mean age of 35.6 +/- 7.9 years. The most
      prevalent risk factor was imprisonment (88.9%) followed by injecting drug use
      (79.2%). The prevalence of HCV infection was 88.5% by ELISA and 86.7% by RIBA,
      while HCV viremia was detected in 26.1% of the patients. HCV-antibody positivity
      was significantly associated with gender, age, marital status, occupation,
      injecting drug use, and history of imprisonment. It was inversely related to
      having an infected or high risk sexual partner. In the logistic regression model,
      the predictors of HCV-positivity were injecting drug use (OR = 24.9, P = 0.004)
      and imprisonment (OR = 21.4, P < 0.001). CONCLUSIONS: Prevalence of HCV infection
      among HIV-positive individuals in our region is very high and there is a need for
      stricter preventive actions against transmission of HCV among this group of
      patients.

PMID- 23878421
TI  - Awareness about Human Papilloma Virus and its Vaccine Among Medical Students.
AB  - BACKGROUND: Cancer of the uterine cervix is the most common malignancy amongst
      women in India. Identification of its pre-cancerous lesions and prevention by HPV
      vaccine may go a long way in decreasing the incidence. AIM: The aim was to study
      the awareness about the various aspects of the HPV infection and vaccine among
      medical students. SETTINGS AND DESIGN: It was a cross-sectional study conducted
      in a tertiary care hospital of Delhi. MATERIALS AND METHODS: 150 medical students
      aged between 18-25 years were requested to complete a 35 point questionnaire
      regarding cervical malignancy, HPV infection, HPV vaccine and the answers were
      then analyzed. RESULTS: None of the students knew the correct incidence of
      cervical cancer in India and 18% of them did not know that the HPV vaccination
      prevents cervical cancer and 50% thought that vaccination induces false sense of
      security. Fifty percent were unaware of HPV infection and its association with
      other STD's and cervical cancer. The information regarding the mechanism of
      action, dosage, schedule and cost of the HPV vaccine was lacking in majority of
      them. The limitation of this study is that it does not reflect the knowledge or
      awareness of a layman or full-fledged medical doctor. CONCLUSIONS: To conclude
      gaps in knowledge regarding HPV infection and vaccination existed amongst the
      medical students and a more integrated teaching regarding HPV carcinogenesis,
      vaccination and cervical cancer needs to be introduced.

PMID- 23878422
TI  - A study on risk factors of breast cancer among patients attending the tertiary
      care hospital, in udupi district.
AB  - BACKGROUND: Cancer has become one of the ten leading causes of death in India.
      Breast cancer is the most common diagnosed malignancy in India, it ranks second
      to cervical cancer. An increasing trend in incidence is reported from various
      registries of national cancer registry project and now India is a country with
      largest estimated number of breast cancer deaths worldwide. AIM: To study the
      factors associated with breast cancer. OBJECTIVES: To study the association
      between breast cancer and selected exposure variables and to identify risk
      factors for breast cancer. MATERIALS AND METHODS: A hospital based Case control
      study was conducted at Shirdi Sai Baba Cancer Hospital and Research Center,
      Manipal, Udupi District. RESULTS: Total 188 participants were included in the
      study, 94 cases and 94 controls. All the study participants were between 25 to 69
      years of age group. The cases and controls were matched by +/- 2 years age range.
      Non vegetarian diet was one of the important risk factors (OR 2.80, CI 1.15
      6.81). More than 7 to 12 years of education (OR 4.84 CI 1.51-15.46) had 4.84
      times risk of breast cancer as compared with illiterate women. CONCLUSION: The
      study suggests that non vegetarian diet is the important risk factor for Breast
      Cancer and the risk of Breast Cancer is more in educated women as compared with
      the illiterate women. LIMITATION: This is a Hospital based study so
      generalisability of the findings could be limited.

PMID- 23878423
TI  - Road traffic accident: an emerging public health problem in assam.
AB  - BACKGROUND: In the northern states, there is hardly any scientific study except
      road traffic accidents (RTAs) statistics obtained by the Ministry of Home whereas
      the main way of transportation is by road. There is the increasing load of motor
      vehicles on the already dilapidated roadways which has resulted in the increasing
      trend of RTAs in Assam. OBJECTIVES: To find out the prevalence, probable
      epidemiological factors and morbidity and mortality pattern due to RTAs in
      Dibrugarh district. MATERIALS AND METHODS: Descriptive study was carried out in
      Dibrugarh district from September 1998 to August 1999 under the department of
      Community Medicine. The information was collected from Assam Medical College and
      Hospital and cross checked with the police report. A medical investigation
      including interview, clinical and radiological investigation was carried out; in
      case of fatality, post-mortem examination was examined in details. An on the spot
      investigation was carried out in accessible RTAs to collect the probable
      epidemiological factors. RESULTS: RTAs affected mainly the people of productive
      age group which were predominantly male. Majority of the RTAs were single vehicle
      accidents and half of the victims were passengers. Accident rate was maximum in
      twilight and winter season demanding high morbidity and mortality. Head and neck,
      U.limb and L.limb were commonly involved. CONCLUSION: RTAs is a major public
      health problem in Assam which needs more scientific study.

PMID- 23878424
TI  - Impact of short term yoga intervention on mental well being of medical students
      posted in community medicine: a pilot study.
AB  - BACKGROUND: High level of stress, anxiety and depression is seen among medical
      students. AIMS: To assess the impact of brief structured yoga intervention on
      mental well being of MBBS students. MATERIALS AND METHODS: The participants
      consisted of 82 MBBS students of 3(rd) semester in the age group of 18-23 years.
      The students were assessed at baseline and at the end of one month of specific
      yoga intervention by using General Health Questionnaire-28 (GHQ-28). RESULTS: The
      students reported improvement in general and mental well being following the
      intervention and difference was found to be highly significant. CONCLUSION: A
      short term specific yoga intervention may be effective in improving general and
      mental well being in MBBS students. It is feasible and practical to include yoga
      practice in block postings of community medicine.

PMID- 23878425
TI  - Magnitude, types and sex differentials of aggressive behaviour among school
      children in a rural area of West Bengal.
AB  - BACKGROUND: Aggression affects academic learning and emotional development, can
      damage school climate and if not controlled early and may precipitate extreme
      violence in the future. OBJECTIVES: (1) To determine the magnitude and types of
      aggressive behavior in school children. (2) To identify the influence of age and
      sex on aggressive behavior. MATERIALS AND METHODS: A cross-sectional study was
      conducted in Anandanagar High School, Singur village, West Bengal. Participants
      were 161 boys and 177 girls of classes VII to IX. The students were asked to
      complete a self-administered questionnaire indicating the types of aggressive
      behavior by them in the previous month and to assess themselves with reference to
      statements indicating verbal/physical aggression. RESULTS: Overall, 66.5% of the
      children were physically aggressive in the previous month: Boys 75.8%, girls
      58.2% (P = 0.001); 56.8% were verbally aggressive: Boys 55.2%, girls 61% (P =
      0.97). Verbal indirect passive aggression was more common among girls (55.3%)
      than among boys (22.3%) (P = 0.000 [1.17E(-09)]). Boys were more liable to
      physical aggression, viz. 60.2% of the boys would hit on provocation compared
      with only 9% of the girls (P = 0.000 [6.6E(-23)]). Regarding attributes
      indicating verbal aggression, girls were more argumentative (63.8%) than boys
      (55.2%) (P = 0.134) and disagreeing (41.8%) compared with boys (33.5%) (P =
      0.145). With increasing age/class, physical direct active aggression decreased
      while physical indirect passive and verbal indirect passive aggression increased.
      No classes had been taken on anger control/management by school the authorities.
      CONCLUSIONS: Aggressive behavior was common both among boys and girls. Life
      skills education/counseling/classroom management strategies are recommended.

PMID- 23878426
TI  - Comparative assessment of satisfaction among outpatient department patients
      visiting secondary and tertiary level government hospitals of a district in
      delhi.

PMID- 23878427
TI  - Effect of maternity schemes on place of delivery in a tribal block of gujarat.

PMID- 23878428
TI  - Insulin resistance and cardio metabolic abnormalities among overweight South
      Indian children: chennai slim and fit programme.

PMID- 23878429
TI  - Why Children are Taking Up the Job?

PMID- 23878430
TI  - Critical incident reporting: Why should we bother?

PMID- 23878431
TI  - Maximum working hours and minimum monitoring standards-need for both to be
      mandatory.

PMID- 23878433
TI  - Logical empiricism in anesthesia: A step forward in modern day clinical practice.

PMID- 23878432
TI  - The fatigued anesthesiologist: A threat to patient safety?
AB  - Universally, anesthesiologists are expected to be knowledgeable, astutely
      responding to clinical challenges while maintaining a prolonged vigilance for
      administration of safe anesthesia and critical care. A fatigued anesthesiologist
      is the consequence of cumulative acuity, manifesting as decreased motor and
      cognitive powers. This results in impaired judgement, late and inadequate
      responses to clinical changes, poor communication and inadequate record keeping.
      With rising expectations and increased medico-legal claims, anesthesiologists
      work round the clock to provide efficient and timely services, but are the "sleep
      provider" in a sleep debt them self? Is it the right time to promptly address
      these issues so that we prevent silent perpetuation of problems pertinent to
      anesthesiologist's health and the profession. The implications of sleep debt on
      patient safety are profound and preventive strategies are quintessential.
      Anesthesiology governing bodies must ensure requisite laws to prevent the adverse
      outcomes of sleep debt before patient care is compromised. 

PMID- 23878434
TI  - A double blind, randomized, controlled trial to study the effect of
      dexmedetomidine on hemodynamic and recovery responses during tracheal extubation.
AB  - BACKGROUND: The alpha2-adrenoreceptor agonist, dexmedetomidine, provides
      excellent sedation with minimal cardiovascular instability or respiratory
      depression and may be a useful adjunct to facilitate smooth tracheal extubation.
      MATERIALS AND METHODS: Fifty American Society of Anesthesiologists grade I-II
      patients, aged 20-45 years, scheduled for elective general surgical, urological
      and gynecological surgeries were studied after randomization into two groups.
      Group A and B, received an intravenous infusion of dexmedetomidine 0.75 mcg/kg or
      placebo respectively, over 15 minutes before anticipated time of end of surgery,
      in a double blind manner. Anesthesia techniques were standardized. Heart rate,
      systolic, diastolic, mean arterial pressures were recorded while starting
      injection, at 1, 3, 5, 10, 15 minutes after starting injection, during
      extubation, at 1, 3, 5 minutes after extubation, and thereafter every 5 minutes
      for 30 minutes. Quality of extubation was evaluated on a 5 point scale and
      postoperative sedation on a 6 point scale. Any event of laryngospasm,
      bronchospasm, desaturation, respiratory depression, vomiting, hypotension, undue
      sedation was noted. RESULTS: Heart rate, systolic, diastolic, mean arterial
      pressures were significantly higher in group B (P < 0.05). Extubation quality
      score of majority of patients was 2 in group A and 3 in group B. Sedation score
      of most patients was 3 in group A and 2 in group B. Bradycardia and hypotension
      incidences were higher in group A. One patient in group A, two patients in group
      B had vomiting. No patient had any other side effects. CONCLUSION:
      Dexmedetomidine 0.75 mcg/kg administered 15 minutes before extubation, stabilizes
      hemodynamics and facilitates smooth extubation.

PMID- 23878435
TI  - Comparison of the effect of lignocaine instilled through the endotracheal tube
      and intravenous lignocaine on the extubation response in patients undergoing
      craniotomy with skull pins: A randomized double blind clinical trial.
AB  - BACKGROUND: A desirable combination of smooth extubation and an awake patient
      after neurosurgical procedures is difficult to achieve in patients with skull
      pins. Lignocaine instilled into endotracheal tube has been reported to suppress
      cough by a local mucosal anesthetizing effect. We aimed to evaluate if this
      effect will last till extubation, if given before pin removal. MATERIALS AND
      METHODS: A total of 114 patients undergoing elective craniotomy were divided into
      three groups and were given 1 mg/kg of intravenous (IV), 2% lignocaine (Group 1),
      placebo (Group 2) and 1 mg/kg of 2% lignocaine sprayed down the endotracheal tube
      (Group 3) before skull pin removal. The effectiveness of each to blunt extubation
      response was compared. Plasma levels of lignocaine were measured 10 min after
      administration of the study drug and at extubation. Sedation scores were noted,
      immediately after extubation and 10 min later. RESULTS: Two percent of lignocaine
      instilled through endotracheal route was not superior to the IV route or placebo
      in attenuating cough or hemodynamic response at extubation when given 20-30 min
      before extubation. The plasma levels of lignocaine (0.8 MUg/ml) were not high
      enough even at the end of 10 min to have a suppressive effect on cough if given
      IV or intratracheally (IT). Lignocaine did not delay awakening in these groups.
      CONCLUSION: IT lignocaine in the dose of 1 mg/kg does not prevent cough at
      extubation if given 20-30 min before extubation. If the action is by a local
      mucosal anesthetizing effect, it does not last for 20-30 min to cover the period
      from pin removal to extubation.

PMID- 23878436
TI  - A prospective randomized double-blind study comparing dexmedetomidine vs.
      combination of midazolam-fentanyl for tympanoplasty surgery under monitored
      anesthesia care.
AB  - BACKGROUND: Analgesia and sedation are usually required for the comfort of the
      patient and surgeon during tympanoplasty surgery done under local anesthesia. In
      this study, satisfaction scores and effectiveness of sedation and analgesia with
      dexmedetomidine were compared with a combination of midazolam-fentanyl. MATERIALS
      AND METHODS: Ninety patients undergoing tympanoplasty under local anesthesia
      randomly received either IV dexmedetomidine 1 MUg kg(-1) over 10 min followed by
      0.2 MUg kg(-1)h(-1) infusion (Group D) or IV midazolam 0.06 mg kg(-1) plus IV
      fentanyl 1 MUg kg(-1) over 10 min (Group MF) followed by normal saline infusion
      at 0.2 ml kg(-1)h(-1). Sedation was titrated to Ramsay sedation score (RSS) of
      three. Vital parameters, rescue analgesics (fentanyl 1 MUg kg(-1)) and sedatives
      (midazolam 0.01 mg kg(-1)), patient and surgeon satisfaction scores were
      recorded. RESULTS: Patient and surgeon satisfaction score was better in Group D
      than Group MF (median interquartile range (IQR) 9 (8-10) vs. 8 (6.5-9.5) and 9
      (8.5-9.5) vs. 8 (6.75-9.25), P = 0.0001 for both). Intraoperative heart rate and
      mean arterial pressure in Group D were lower than the baseline values and the
      corresponding values in Group MF (P < 0.05). Percentage of patients requiring
      rescue fentanyl was higher in Group MF than Group D (40% vs. 11.1%, P = 0.01).
      One patient in Group D while four in Group MF (8.8%) required rescue sedation
      with midazolam (P > 0.17). Seven patients in Group D had dry mouth vs. none in
      Group MF (P = 0.006). One patient in Group D had bradycardia with hypotension
      which was effectively treated. CONCLUSION: Dexmedetomidine is comparable to
      midazolam-fentanyl for sedation and analgesia in tympanoplasty with better
      surgeon and patient satisfaction. Hemodynamics need to be closely monitored.

PMID- 23878437
TI  - A comparative study to evaluate the effect of intranasal dexmedetomidine versus
      oral alprazolam as a premedication agent in morbidly obese patients undergoing
      bariatric surgery.
AB  - BACKGROUND: Morbidly obese patients with obstructive sleep apnea are extremely
      sensitive to sedative premedication. Intranasal dexmedetomidine is painless and
      quick acting. Intranasal dexmedetomidine can be used for premedication as it
      produces adequate sedation and also obtund hemodynamic response to laryngoscopy
      and tracheal intubation. MATERIALS AND METHODS: Forty morbidly obese patients
      with BMI > 35 were chosen and divided into two groups. Group DEX received
      intranasal dexmedetomidine 1 mcg/kg (ideal body weight) while other group (AZ)
      received oral alprazolam 0.5 mg. Sedation scale, heart rate and the mean arterial
      pressure was assessed in both the groups at 0 hour, 45 minutes, during
      laryngoscopy and tracheal intubation. RESULTS: The demographic profile, baseline
      heart rate, means arterial pressure, oxygen saturation and sedation scale was
      comparable between the two groups. The sedation scores, after 45 min, were
      statistically significant between the two groups i.e., 2.40 +/- 1.09 in the AZ
      group as compared to 3.20 +/- 1.79 in DEX group P value 0.034. The heart rate,
      mean arterial pressure and oxygen saturation were statistically similar between
      the two groups, after 45 min. The heart rate was significantly lower in the DEX
      group as compared to the AZ group. There was no statistical difference in the
      mean arterial pressure between the two groups either during laryngoscopy or
      tracheal intubation. CONCLUSION: Intranasal dexmedetomidine is a better
      premedication agent in morbidly obese patients than oral alprazolam.

PMID- 23878438
TI  - The prediction of difficult intubation in obese patients using mirror indirect
      laryngoscopy: A prospective pilot study.
AB  - BACKGROUND: The incidence of difficult laryngoscopy and intubation in obese
      patients is higher than in the general population. Classical predictors of
      difficult laryngoscopy and intubation have been shown to be unreliable. We
      prospectively evaluated indirect mirror laryngoscopy as a predictor of difficult
      laryngoscopy in obese patients. MATERIALS AND METHODS: 60 patients with a body
      mass index (BMI) greater than 30, scheduled to undergo general anesthesia, were
      enrolled. Indirect mirror laryngoscopy was performed and was graded 1-4 according
      to Cormack and Lehane. A view of grade 3-4 was classified as predicting difficult
      laryngoscopy. Additional assessments for comparison were the Samsoon and Young
      modification of the Mallampati airway classification, Wilson Risk Sum Score, neck
      circumference, and BMI. The view obtained upon direct laryngoscopy after
      induction of general anesthesia was classified according to Cormack and Lehane as
      grade 1-4. RESULTS: Sixty patients met the inclusion criteria; however, 8 (13.3%)
      patients had an excessive gag reflex, and examination of the larynx was not
      possible. 15.4% of patients who underwent direct laryngoscopy had a Cormack and
      Lehane grade 3 or 4 view and were classified as difficult. Mirror laryngoscopy
      had a tendency toward statistical significance in predicting difficult
      laryngoscopy in these patients. CONCLUSIONS: This study is consistent with
      previous studies, which have demonstrated that no one individual traditional test
      has proven to be adequate in predicting difficult airways in the obese
      population. However, the new application of an old test - indirect mirror
      laryngoscopy - could be a useful additional test to predict difficult
      laryngoscopy in obese patients.

PMID- 23878439
TI  - Predicting difficult laryngoscopy in acromegalic patients undergoing surgery for
      excision of pituitary tumors: A comparison of extended Mallampati score with
      modified Mallampati classification.
AB  - BACKGROUND: There are numerous reports of difficult laryngoscopy and intubation
      in patients with acromegaly. To date, no study has assessed the application of
      extended Mallampati score (EMS) for predicting difficult intubation in
      acromegalics. The primary aim of this study was to compare EMS with modified
      Mallampati classification (MMP) in predicting difficult laryngoscopy in
      acromegalic patients. We hypothesized that since EMS has been reported to be more
      specific and better predictor than MMP, it may be superior to the MMP to predict
      difficult laryngoscopy in acromegalic patients. MATERIALS AND METHODS: For this
      prospective cohort study with matched controls, acromegalic patients scheduled to
      undergo pituitary surgery over a period of 3 years (January 2008-December 2010)
      were enrolled. Preoperative airway assessment was performed by experienced
      anesthesiologists and involved a MMP and the EMS. Under anesthesia, laryngoscopic
      view was assessed using Cormack-Lehane (CL) grading. MMP and CL grades of I and
      II were defined "easy" and III and IV as "difficult". EMS grade of I and II were
      defined "easy" and III as "difficult". Data were used to determine the
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of MMP and EMS in predicting difficult laryngoscopy. RESULTS:
      Seventy eight patients participated in the study (39 patients in each group).
      Both MMP and EMS failed to detect difficult laryngoscopy in seven patients. Only
      one laryngoscopy was predicted to be difficult by both tests which was in fact,
      difficult. CONCLUSION: We found that addition of neck extension did not improve
      the predictive value of MMP.

PMID- 23878440
TI  - Predictive value of upper lip bite test and ratio of height to thyromental
      distance compared to other multivariate airway assessment tests for difficult
      laryngoscopy in apparently normal patients.
AB  - BACKGROUND: Various anatomical measurements and non-invasive clinical tests,
      singly or in various combinations can be performed to predict difficult
      intubation. Recently introduced "Upper lip bite test" (ULBT) and "Ratio of height
      to Thyromental distance" (RHTMD) are claimed to have high predictability. We
      conducted a study to compare the Predictive Value of ULBT and RHTMD with Mouth
      opening (Inter-Incisor gap) (IIG), Modified Mallampatti Test (MMT), Head and neck
      movement (HNM) and Thyromental Distance (TMD) for Difficult Laryngoscopy.
      MATERIALS AND METHODS: In this prospective, single blinded observational study,
      480 adult patients of either sex, ASA grade I and II were assessed and graded for
      ULBT, RHTMD, TMD, MMT, IIG, and HNM according to standard methods and correlated
      with the Cormack and Lehane grade. RESULTS: ULBT and RHTMD had highest
      sensitivity, specificity, positive predictive value, negative predictive value,
      likelihood ratio, i.e., 74.63%, 91.53%, 58.82%, 95.7%, 31.765 and 71.64%, 92.01%,
      59.26%, 95.24%, 8.96 respectively, compared to TMD, MMT, IIG and HNM.
      CONCLUSIONS: ULBT is the best predictive test for difficult laryngoscopy in
      apparently normal patients but RHTMD can also be used as an acceptable
      alternative.

PMID- 23878441
TI  - Comparison of hemodynamic response to tracheal intubation with Macintosh and
      McCoy laryngoscopes.
AB  - BACKGROUND: Use of McCoy blade laryngoscope avoids the lifting force in the
      vallecula and theoretically should lead to a lower hemodynamic response related
      to laryngoscopy and tracheal intubation. The available literature on the topic is
      conflicting. MATERIALS AND METHODS: We studied the hemodynamic response to
      laryngoscopy and tracheal intubation in 60 ASA 1 AND 2 adult patients using
      either Macintosh or McCoy laryngoscopes. The change in systolic, diastolic, mean
      arterial pressure, and heart rate (HR) was observed for 10 min post intubation.
      Arrhythmias and ST changes were also observed. RESULTS: The maximum change in HR
      was 18.7% in the Macintosh and 7.7% in the McCoy group, and in systolic arterial
      pressure was 22.9% in the Macintosh and 10.3% in the McCoy group. This difference
      between groups was significant (P < 0.0001). The change lasted for a lesser
      duration in the McCoy group. No arrhythmias or ST changes were observed in either
      group. CONCLUSION: Hemodynamic changes with use of McCoy laryngoscope were lesser
      in magnitude and of shorter duration.

PMID- 23878442
TI  - Post-operative pulmonary complications in patients undergoing transoral
      odontoidectomy and posterior fixation for craniovertebral junction anomalies.
AB  - BACKGROUND: In patients with craniovertebral junction (CVJ) anomalies, the
      respiratory system is adversely affected in many ways. The sub-clinical
      manifestations may get aggravated in the postoperative period owing to anesthetic
      or surgical reasons. However, there is limited data on the incidence of
      postoperative pulmonary complications (PPCs) and associated risk factors in such
      patients, who undergo transoral odontoidectomy (TOO) and posterior fixation (PF)
      in the same sitting. MATERIALS AND METHODS: Five years data of 178 patients with
      CVJ anomaly who underwent TOO and PF in the same sitting were analyzed
      retrospectively. Preoperative status, intraoperative variables, and PPCs were
      recorded. Patients were divided into two groups depending on the presence or
      absence of PPCs. Bivariate analysis was done to find out association between
      various risk factors and PPCs. Multivariate analysis was done to detect relative
      contribution of the factors shown to be significant in bivariate analysis. P <
      0.05 was considered as significant. RESULTS: The incidence of PPCs was found to
      be 15.7%. Factors significantly associated with PPCs were American Society of
      Anesthesiologists grade higher than II, preoperative lower cranial nerves palsy
      and respiratory involvement, duration of surgery, and intraoperative blood
      transfusion. In multivariate analysis, blood transfusion was found to be the sole
      contributing factor. The patients who developed PPCs had significantly prolonged
      stay in ICU and hospital. CONCLUSION: Patients with CVJ anomaly are at increased
      risk of developing PPCs. There is a strong association between intraoperative
      blood transfusion and PPCs. Patients with PPCs stay in the ICU and hospital for a
      longer period of time.

PMID- 23878443
TI  - Betahistine as an add-on: The magic bullet for postoperative nausea, vomiting and
      dizziness after middle ear surgery?
AB  - PURPOSE: Patients undergoing middle ear surgery experience variable degrees of
      postoperative nausea and vomiting (PONV) despite prophylaxis and treatment with
      ondansetron or other 5HT3 receptor antagonists. Furthermore vertigo or dizziness
      are not well controlled perioperatively. Role of betahistine was tested as an add
      on to ondansetron in control of PONV and vertigo in middle ear surgery cases.
      MATERIALS AND METHODS: We conducted a prospective, randomized, double-blind,
      placebo controlled study, enrolling one hundred patients undergoing middle ear
      surgery under local anesthesia into two groups consisting of fifty (n = 50)
      patients each. Group A patients were given betahistine 16 mg plus ondansetron 8
      mg and placebo plus ondansetron 8 mg were given to group B or placebo group,
      orally 3 hours before starting operation. The incidence of nausea, vomiting, and
      dizziness was noted during the intraoperative and postoperative 24 hours period.
      Chi-square test, unpaired 't' test, and Fisher's exact tests were performed for
      statistical analysis using SPSS version 16 and Open Epi version 2.3.1 softwares.
      RESULTS: Complete response was obtained in 90% patients in the betahistine group
      as compared to 66% in the placebo group. Vomiting in the intraoperative and
      postoperative period was noted in 4% and 8% cases, respectively, in the
      betahistine group as compared to 18% and 26%, respectively, in the placebo group.
      Overall, vertigo was 10% versus 32% in betahistine group and placebo group,
      respectively. CONCLUSION: Betahistine as an add-on to ondansetron can
      significantly attenuate PONV and perioperative vertigo, following middle ear
      surgeries.

PMID- 23878444
TI  - Perioperative anesthetic documentation: Adherence to current Australian
      guidelines.
AB  - PURPOSE: The lack of adequate perioperative documentation has legal implications
      and can potentially affect the quality and safety of patient care. Despite the
      presence of guidelines, the adequacy of perioperative documentation in
      Australasia has not been adequately assessed. The aim of this study is to assess
      the adequacy of anesthetic documentation on the pre and intraoperative encounters
      and to test the hypotheses that documentation is incomplete in the settings of
      emergency vs. elective procedures, regional vs. general anesthesia, and manual
      vs. electronic documentation. MATERIALS AND METHODS: The study was an
      observational retrospective study in the setting of a 250-bed teaching hospital
      in metropolitan Adelaide, Australia. The perioperative records of 850 patients
      were analyzed. A scoring system was designed, based on a policy statement from
      the Australian and New Zealand College of Anesthetists and a survey of the
      hospital anesthetists. Scored and categorical data was analyzed using Chi-square
      test. Numerical data was analyzed using student t-test. The null hypothesis was
      accepted or rejected at 0.05 significance. RESULTS: There were significant
      deficiencies in the adequacy of preanesthetic and intraoperative records. This
      has been shown to be true in all cases. Documentation was found to be poorer in
      the emergency setting when compared to elective cases (median scores 15 vs. 21 P
      = 0.03) as well as documentation of airway assessment for cases done solely under
      regional anesthesia (42 vs. 85%, P = 0.05). There were no significant differences
      in the adequacy of electronic vs. manual records (P = 0.92). CONCLUSION: There
      are significant deficiencies in the adequacy of perioperative records. This has
      been shown to be true in all cases, but is especially so in emergency cases and
      for patients having only regional anesthesia.

PMID- 23878445
TI  - Presentation of research in anesthesia: Culmination into publication?
AB  - BACKGROUND: To assess the quality of research presentations made in conferences,
      its success or failure to be published in a peer-reviewed journal is a well
      accepted marker. However, there is no data regarding the publication of research
      presentations made in Indian conferences of anesthesiology. OBJECTIVE: The
      primary objective was to determine publication rate of research presented at the
      largest and best attended national conference in anesthesiology, the Indian
      Society of Anaesthesiologists' Conference (ISACON), and also compare it with the
      rate from an international conference American Society of Anesthesiologists (ASA
      annual meeting) held in the same year. MATERIALS AND METHODS: All 363 abstracts
      presented as poster or podium presentations at the ISACON, and an equal number of
      randomly selected abstracts presented at ASA annual meeting were searched on
      Pubmed and Google Scholar for their full-text publications in peer-reviewed
      journals using a standardized search strategy. As secondary observations,
      abstracts were assessed for completeness by noting certain components central to
      research methodology. Also, changes between abstract of the presentation and
      published paper were noted with respect to certain components. RESULTS: The
      publication rate of presentations at ISACON and ASA meetings was 5% and 22%,
      respectively. The abstracts from ISACON lacked central components of research
      such as methods and statistical tests. The commonest change in the full-text
      publications as compared with the original abstract from both conferences was a
      change in authorship. CONCLUSION: Steps are required to augment full-text
      publication of Indian research, including a more rigorous peer review of
      abstracts submitted to ISACON to ensure their completeness.

PMID- 23878446
TI  - Firstborn offspring sex ratio is skewed towards female offspring in anesthesia
      care providers: A questionnaire-based nationwide study from United States.
AB  - BACKGROUND: A parental occupation such as anesthesia care provider can involve
      exposure of the parent to various chemicals in the work environment and has been
      correlated to skewed offspring sex ratios. OBJECTIVES: The objective was to
      conduct a nation-wide survey to observe (a) whether firstborn offspring sex ratio
      (OSR) in anesthesia providers is skewed towards increased female offspring, and
      (b) to identify potential factors influencing firstborn OSR, particularly those
      relating to the peri-conceptional practice of inhalational anesthesia induction
      among anesthesia providers. MATERIALS AND METHODS: After institutional review
      board approval, a questionnaire was uploaded on SurveyMonkey and sent to
      anesthesia providers through their program coordinators in United States (US) to
      complete the survey. RESULTS: The current US national total-population sex ratio
      is 0.97 male (s)/female with an at-birth sex ratio of 1.05 male (s)/female;
      comparatively, the results from anesthesia providers' survey respondents (n =
      314) were a total OSR of 0.93 male (s)/female (P = 0.61) with firstborn OSR 0.82
      male (s)/female (a 6% increase in female offspring; P = 0.03), respectively. The
      only significant peri-conceptional factor related to anesthesia providers'
      firstborn OSR's skew was inhalational induction practice by anesthesia care
      provider favoring female offspring (P < 0.01). CONCLUSION: Based on the results
      of this limited survey, it can be concluded that anesthesia care providers who
      practice inhalation induction of anesthesia during the peri-conceptional period
      are significantly more likely to have firstborn female offspring.

PMID- 23878447
TI  - Rural perspective about anesthesia and anesthesiologist: A cross-sectional study.
AB  - BACKGROUND: More than 3/4(th) of Indian population resides in rural areas. The
      public awareness towards "Anesthesia and Anesthesiologist" is limited even in
      urban population. There is no data available from rural India on this
      perspective. Our cross-sectional analysis highlights this lack of public
      awareness and discusses possible remedies to overcome these limitations.
      MATERIALS AND METHODS: Surgical outpatient department of Comprehensive Rural
      Health Center (CRHC) Ballabgarh, Haryana (model CRHC for Indian health schemes)
      was screened for 6 months period. A questionnaire divided into 3 parts (Awareness
      about Anesthesiologist, Consent, Present surgical experience) was filled out for
      each patient. The patients on the basis of their answers were classified as
      "aware or unaware", also source of patient information was analyzed. RESULTS:
      Even with an extremely low threshold, only 36.44% of population could be
      classified as aware, and commonest source of their information was not
      anesthesiologist but surgeon (64.32%). 83.6% patients were not aware of contents
      of pre-operative consent they had signed and further, only 3.4% were aware of
      anesthesia-related issues. Pain was reported as the most common pre-operative
      fear and post-operative patient concern. 47.17% patients due to lack of pre
      operative counseling were not able to recognize the type of anesthesia and
      thought they had received both general anesthesia and spinal anesthesia. At the
      end, after explaining the role of anesthesia for surgery, 99.06% patients
      presented desire to meet the anesthesiologist beforehand if they were to be
      operated in future. CONCLUSION: The rural awareness about anesthesia is extremely
      low likely because of low literacy rates and lack of pre-operative counseling by
      anesthesiologist. Both patient and anesthesiologist must understand the
      importance of consent, as it is not only a legal binding but can eliminate pre
      operative factitious fears of patients and can improve patient satisfaction
      towards surgery.

PMID- 23878448
TI  - Novel use of laryngeal mask airway classic excelTM for bronchoscopy and tracheal
      intubation.
AB  - The usage frequency and scope of supraglottic airway devices in anesthesia has
      expanded since the original laryngeal mask airway (LMA) prototype was invented by
      Dr Archie Brain in the early 1980s. Today, anesthesiologists are spoilt-for
      choice with more than thirty options. The LMA Classic ExcelTM was introduced to
      anesthesia practice in 2009; designed with an epiglottic elevating bar and a
      removable airway connector to facilitate tracheal intubation using the LMA as a
      conduit. We present a case report of a women diagnosed with papillary carcinoma
      of thyroid, who underwent bronchoscopic assessment of the trachea and subsequent
      intubation for an en-bloc dissection and removal of thyroid gland through the LMA
      Classic ExcelTM. 

PMID- 23878449
TI  - Tracheal extubation under deep sevoflurane anesthesia: A novel strategy for
      weaning difficulties in intensive care.
AB  - Various criteria for weaning patients from ventilators in intensive care have
      been widely published. These criteria are increasingly incorporated into
      guidelines, protocols, and more recently, care pathways. We present a case where
      a patient's lungs were ventilated for 4 days with an infective exacerbation of
      chronic obstructive pulmonary disease (COPD). We successfully weaned off
      mechanical ventilation and rapidly extubated the patient's trachea utilizing deep
      sevoflurane anesthesia. Published weaning indices suggest that this would have
      been an inappropriate course of action at the time. However, our patient clearly
      benefited and avoided the need for tracheostomy and prolonged ventilation. 

PMID- 23878450
TI  - Severe autonomic dysreflexia induced cardiac arrest under isoflurane anesthesia
      in a patient with lower thoracic spine injury.
AB  - We present a case of severe autonomic dysreflexia (AD) progressing to cardiac
      arrest and death under isoflurane anesthesia. Though AD in chronic cervical spine
      injury is a common entity, occurrence of such an event in the stage of flaccid
      paralysis in lower dorsal spinal cord injury is rare, especially under general
      anesthesia. Manipulation of urinary bladder catheter under light plane of
      isoflurane anesthesia might be the precipitating factor. Increasing concentration
      of isoflurane failed to abort the episode or might have aggravated it. High level
      of suspicion and vigilance is necessary to prevent, diagnose and treat such a
      condition. 

PMID- 23878452
TI  - Aortic valve replacement in a patient with systemic lupus erythematosus.
AB  - Valvular heart disease in systemic lupus erythematosus (SLE) is associated with
      substantial morbidity and mortality. Current therapy includes symptomatic
      measures and valve replacement. SLE can present major challenges because of
      accrued organ damage, coagulation defects and complex management regimes. The
      peri-operative goals are to maintain strict asepsis, avoid use of nephrotoxic
      drugs and thereby renal insult, and to promote early ambulation post-operatively.

PMID- 23878451
TI  - A surgeon's assessment of inadequate neuromuscular antagonism in a case of
      prolonged neuromuscular blockade.
AB  - Evaluation of the degree of neuromuscular blockade by the surgeon using clinical
      criteria alone is unreliable. We report a case of prolonged neuromuscular
      blockade lasting 5.5 h, where an additional intra-operative dose of neuromuscular
      relaxant was given at the request of the surgical team. Possible causes of
      prolonged neuromuscular antagonism are discussed, as is the importance of
      neuromuscular assessment prior to the administration of additional neuromuscular
      blocking agents when receiving a surgeon request for additional
      neuromuscularblockade. 

PMID- 23878453
TI  - Anesthetic management of an infant for aortopexy.
AB  - Tracheomalacia is a rare condition characterized by weakness of tracheobronchial
      cartilaginous bridges. Severe weakness results in tracheal collapse during
      inspiration, obstructing normal airflow. Tracheomalacia may also be associated
      with esophageal atresia, tracheoesophageal fistula, and gastroesophageal reflux.
      Aortopexy is an established surgical procedure for treatment of severe
      tracheomalacia. A 2-month-old boy was scheduled for aortopexy. He had already
      undergone repair of tracheoesophageal fistula and had failed multiple attempts at
      extubation. Intraoperative flexible fiberoptic bronchoscopy was performed to
      guide the amount and direction of aortopexy for assuring the most effective
      tracheal decompression. Since tracheomalacia is best assessed in a spontaneously
      breathing patient, it was an anesthetic challenge to maintain an adequate depth
      of anesthesia while allowing the patient to breathe spontaneously. Throughout the
      intraoperative period, SpO2 remained >=96%. Following the procedure, the trachea
      was extubated and patient was able to breathe normally. 

PMID- 23878455
TI  - Severe aortic stenosis and subarachnoid hemorrhage: Anesthetic management of
      lethal combination.
AB  - Despite advances in various modalities of management, subarachnoid hemorrhage
      (SAH) continues to be associated with high mortality, which is further increased
      by associated comorbidities. Aortic stenosis (AS) is one such disease which can
      further complicate the course of SAH. We recently managed a known patient of
      severe AS, who presented with aneurysmal SAH. Patient was planned for
      eurovascular intervention. With proper assessment and planning, patient was
      managed with favorable outcome despite the restrictions faced in the
      neurovascular intervention laboratory. 

PMID- 23878456
TI  - Safe intubation in Morquio-Brailsford syndrome: A challenge for the
      anesthesiologist.
AB  - Morquio-Brailsford syndrome is a type of mucopolysaccharidoses. It is a rare
      disease with features of short stature, atlantoaxial instability with risk of
      cord damage, odontoid hypoplasia, pectus carinatum, spine deformities,
      hepatomegaly, and restrictive lung disease. Neck movements during intubation are
      associated with the risk of quadriparesis due to cervical instability. This,
      along with the distortion of the airway anatomy due to deposition of
      mucopolysaccharides makes airway management arduous. We present our experience in
      management of difficult airway in a 3-year-old girl with Morquio-Brailsford
      syndrome posted for magnetic resonance imaging and computerized tomography scan
      of a suspected unstable cervical spine. As utmost sagacity during intubation is
      required, the child was intubated inside operation theatre in the presence of
      experienced anesthesiologists and then shifted to the peripheral location.
      Intubation was done with an endotracheal tube railroaded over a pediatric
      fibreoptic bronchoscope passed through the lumen of a classic laryngeal mask
      airway, keeping head in neutral position. 

PMID- 23878457
TI  - Massive lingual swelling following cleft palate repair.
AB  - We report two cases of massive tongue edema in routine palatoplasty. All patients
      had uneventful recovery. We postulated that the macroglossia was secondary to
      ischemia and venous congestion after prolonged use of Killner Dott mouth gag with
      slotted tongue blade exaggerated by hyperextension of neck and Trendelenberg
      position. 

PMID- 23878458
TI  - A rare complication of mandibular surgery: Something to chew on!

PMID- 23878459
TI  - Intra-operative Tako-tsubo cardiomyopathy during carotid body tumor excision: An
      indication for therapeutic use of Levosimendan.

PMID- 23878460
TI  - Non conventional way of securing endotracheal tube in a case of facial burns.

PMID- 23878461
TI  - In response to: Midazolam-induced acute dystonia reversed by diazepam.

PMID- 23878462
TI  - Authors' reply.

PMID- 23878463
TI  - Eosinophilia in pre-anesthetic assessment: A guide to diagnosis of DRESS
      syndrome.

PMID- 23878464
TI  - Anesthetic management of difficult airway in a patient with massive neurofibroma
      of face: Utility of Rendell Baker Soucek mask and left molar approach for
      ventilation and intubation.

PMID- 23878465
TI  - Post-operative unmasked bilateral vocal cord palsy attributed to pre-operative
      radiotherapy.

PMID- 23878466
TI  - Incidental internal jugular vein thrombosis in a patient with intracranial
      aneurysm: Implications for the anesthesiologists.

PMID- 23878467
TI  - Anesthetic management of a rare presentation of pediatric blunt chest trauma.

PMID- 23878468
TI  - Paratracheal cyst rupture: A false alarm for tracheal rupture.

PMID- 23878469
TI  - Peculiar breathing in Rett syndrome: Anesthesiologist's nightmare.

PMID- 23878470
TI  - Anesthesia for percutaneous nephrolithotomy in a case of Kartagener's syndrome.

PMID- 23878471
TI  - Chest tube and air travel "Patient worsening and improving spontaneously".

PMID- 23878472
TI  - Video laryngoscopy added fiberoptic intubation in a patient with difficult
      airway.

PMID- 23878473
TI  - Bronchospasm: Not always the cause for tight bag.

PMID- 23878474
TI  - Malfunction of heat and moisture exchanger filters: Causality or unresolved
      problem?

PMID- 23878475
TI  - Failed ventilation due to heat and moisture exchange filter malfunction: A
      difficult diagnostic scenario.

PMID- 23878476
TI  - Airway obstruction following intubation using a bonfils rigid intubating
      fiberscope and polyvinylchloride tracheal tube.

PMID- 23878477
TI  - Triple negative breast cancer: A continuing challenge.

PMID- 23878478
TI  - A clinical survey of laryngectomy patients to detect presence of the false
      perception of an intact larynx or the "phantom larynx" phenomenon.
AB  - HYPOTHESIS: The Phantom larynx phenomenon (the false perception on an intact
      larynx in a laryngectomee) exists and is an important issue in the post
      laryngectomy rehabilitation of such patients. OBJECTIVES: The phantom limb
      phenomenon has been described after amputation of a limb or other parts of the
      body. Amputation or removal of any part is usually associated with a global
      feeling that the missing part is still present. We undertook this study to
      identify whether a phantom larynx phenomenon actually exists in laryngectomees.
      We also aimed to elicit its association with the duration following surgery.
      PATIENTS AND METHODS: We did a clinical survey of 66 post-laryngectomy patients
      (30-80 years of age). Twenty-two of these patients were assessed within 6 months
      following surgery, whereas 44 patients were assessed at least 6 months later. A
      questionnaire containing 11 questions was served to these laryngectomees
      pertaining to false perception of persistent laryngeal functions and adaptation
      to the post-laryngectomy status. RESULTS: All patients showed an evidence of a
      phantom larynx phenomenon. In the majority of these patients, it persisted even
      after 6 months following surgery. There was no significant difference in the two
      groups (less than or more than 6 months) except for one question pertaining to
      occlusion of stoma for speech (77% vs. 29%). False perception of nasal breathing
      (59% and 43%) and olfactory sensation (63% in both groups) were the most common.
      CONCLUSION: Phantom larynx phenomenon following laryngectomy exists and may cause
      anxiety and poor rehabilitation among patients. Education and rehabilitation with
      regards to such a phenomenon is therefore needed in all patients.

PMID- 23878479
TI  - Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy
      among children for whom radiotherapy and chemotherapy are used for treatment.
      When hypothalamus-pituitary axis is exposed to radiotherapy, children's hormone
      level and quality of life are influenced. The aim of this study is to determine
      late effects of radiotherapy on hormonal level in these patients. MATERIALS AND
      METHODS: In this study 27 children with ALL, who have been referred to Shahid
      Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole
      brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These
      patient's basic weight, height and hormonal levels were measured before
      radiotherapy and also after different periods of time. RESULTS: GHD (growth
      hormone deficiency) after clonidine stimulation test was observed in 44% (n=12)
      and that in 50% of them (n=6), less than 1 year, had been passed from their
      radiation therapy. None of these patients demonstrated hormone deficiency in
      other axes. CONCLUSIONS: This study showed that even application of a 18-24 Gy
      radiation dose might influence growth hormone levels; therefore, we recommend
      reduction of radiotherapy dose in such patients whenever possible.

PMID- 23878480
TI  - Palliative chemotherapy in head and neck squamous cell cancer - What is best in
      Indian population? A time without symptoms, treatment toxicity score based study.
AB  - BACKGROUND: Patients with recurrent and metastatic head and neck Squamous Cell
      Cancer (HNSCC) have poor prognosis with limited treatment options. In view of
      decimal prognosis, the treatment decision should include quality of life (QOL)
      issues, cost-effectiveness besides the response rates and survival. AIM: Present
      retrospective analysis was conducted to evaluate efficacy (disease-free
      survival), pharmacoeconomics, and toxicity profile of four (4) different
      regimens, viz. gefitinib alone, gefitinib with methotrexate, methotrexate alone,
      or 5-FU with cisplatin. MATERIALS AND METHODS: Case records between 2007
      September and 2008 September were analyzed, 68 patients were found suitable for
      analysis. Patients received gefitinib (250 mg/day), methotrexate as 50 mg
      intramuscular weekly or a combination of the same or 5-FU 750 mg/m(2)/day for 4
      days along with cisplatin 75 mg/m(2)/day on day 1 in 21-day cycle. RESULTS: A
      total of 68 patients received therapy. Fifty-one patients have clinically
      meaningful response (stable disease + complete + partial responses) (75%) and had
      symptomatic improvement. The median progression-free survival was significantly
      superior in responders (those who achieved partial or complete response) (8.4
      months vs. 3.1 months, P=0.001). Methotrexate with gefitinib had maximum median
      survival and better overall QOL compared to the other treatment regimens. Weekly
      methotrexate is relatively cost-effective followed by methotrexate with gefitinib
      and gefitinib alone. 5-FU with cisplatin in our experience does not appear so
      attractive in view of high complication rates (when given in full doses) and
      prolonged hospital stay. CONCLUSION: Based on the results of this retrospective
      analysis, methotrexate weekly as single agent or in combination with gefitinib
      appears as an attractive alternative regimen for patients with metastatic HNSCC
      including those having poor performance status. A prospective study was planned
      and submitted to the local ethics committee based on above results to validate
      these results and compare methotrexate and gefitinib arm with 5-FU + cisplatin.

PMID- 23878481
TI  - Deferasirox in Indian children with thalassemia major: 3 years experience.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the oral iron chelator
      deferasirox in treating transfusional hemosiderosis in a cohort of Indian
      children with thalassemia major with high iron load. MATERIALS AND METHODS: The
      first 50 children (age 2-18 yrs) with thalassemia major to commence deferasirox
      at our center were enrolled and followed up for a period of 36 months between
      April 2008 and March 2011. The dose of deferasirox was determined by their
      baseline serum ferritin and was adjusted to a maximum of 40 mg/kg/day depending
      on response. Ferritin levels, SGOT, SGPT, serum creatinine and urine albumin were
      regularly monitored. RESULTS: Of the 50 patients, 76% documented a significant
      decline in serum ferritin (P<0.05). Seven (14%) patients had a stable ferritin
      whilst 5 patients (10%) documented an increase over the study period. The mean
      serum ferritin at baseline, 12, 24 and 36 months was 4354, 3260, 3290 and 3042,
      respectively (P<0.05). The median serum ferritin at the same time points was
      3555, 2810, 2079 and 2271, respectively (P<0.05). No severe toxicity was seen.
      CONCLUSIONS: Deferasirox, when given in doses >=30 mg/kg, was found to be an
      effective and safe drug in reducing transfusional hemosiderosis. Thirty five
      (70%) needed dose escalation upto 40 mg/kg/day. Fifteen (30%), however did not
      achieve a negative iron balance despite maximally permissible doses.

PMID- 23878482
TI  - Collision tumor of kidney: A case of renal cell carcinoma with metastases of
      prostatic adenocarcinoma.
AB  - Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is
      well documented in the literature. However, metastatic prostatic adenocarcinoma
      in a kidney harboring a renal cell carcinoma (RCC) is quite rare. Although renal
      cell carcinoma is the most common tumor that can harbor metastasis, metastatic
      prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are
      four cases in the literature showing metastasis of prostatic adenocarcinoma to
      RCC. However, as per our knowledge, this is the first case of a collision between
      RCC and metastatic prostatic adenocarcinoma. 

PMID- 23878483
TI  - Resistant metastatic penile carcinoma and response to biochemotherapy with
      paclitaxel and epidermal growth factor receptor monoclonal antibody, nimotuzumab.
AB  - Carcinoma penis is one of the common malignancies in developing world especially
      among rural population. Multimodality treatment with surgery, radiation and
      chemotherapy for advanced penile carcinoma with groin nodal metastasis is crucial
      to optimise the outcome. Cisplatin, fluorouracil, methotrexate, vinorelbine,
      bleomycin and paclitaxel are the common chemotherapeutic agents used along with
      local therapy. Paucity of data to show superiority of one chemotherapeutic regime
      over another and only modest response to any combination chemotherapy.
      Progression of disease after surgery, radiation and chemotherapy is associated
      with poor outcome and quality of life. Nimotuzumab, Anti EGFR monoclonal
      antibody, along with paclitaxel in our case of resistant metastatic penile
      carcinoma has shown good symptomatic palliation and clinical response. 

PMID- 23878484
TI  - Candida albicans endocarditis in a child with acute lymphoblastic leukemia: A
      dreaded complication of intensive chemotherapy.
AB  - Candida endocarditis is a rare entity during febrile neutropenia due to early
      introduction of empirical antifungal therapy. Early surgical intervention has
      diagnostic and therapeutic importance in Candida endocarditis. We report a case
      of Candida albicans endocarditis in a child with acute lymphoblastic leukemia on
      chemotherapy. The role of surgical intervention is discussed. 

PMID- 23878485
TI  - Adrenal metastases in a post-radiation malignant fibrous histiocytoma after low
      dose radiation for a benign condition.
AB  - A 29-year-old male presented with an aggressive malignant fibrous histiocytoma of
      his leg 14 years after he had received low-dose radiation to the area for a
      benign indication. The other unusual feature of this case was the large
      unilateral adrenal metastasis. We describe this very rare presentation of sarcoma
      and briefly review the relevant literature. 

PMID- 23878486
TI  - Case of childhood laryngeal papillomatosis with metastatic carcinoma esophagus in
      adulthood.
AB  - A young male patient was diagnosed to have laryngeal papillomas at the age of 3
      years for which he underwent permanent tracheostomy and also multiple surgical
      and laser excision procedures. Then, later in life, the patient had progressive
      breathlessness and dysphagia. On examination, he had supraclavicular
      lymphadenopathy showing squamous carcinoma pathology. Since laryngeal papillomas
      have a high propensity to transform into laryngeal squamous cell carcinoma, he
      was first evaluated for laryngeal carcinoma which was negative. Esophagoscopy
      showed a growth in the esophagus, the biopsy of which was positive for squamous
      malignant cells. Patient was then started on palliative chemotherapy with
      combination of paclitaxel and carboplatin, and at progression with weekly nanoxel
      with stable disease. This is a rare case of childhood laryngeal papillomatosis
      progressing to metastatic esophageal carcinoma. This case has been presented to
      highlight the fact that patients with laryngeal papillomas are not only at high
      risk of progressing to laryngeal carcinoma but can also have other malignancies
      of the upper aerodigestive tract and lung. Most of them have been correlated to
      human papilloma virus (HPV), but in our patient HPV DNA was negative. 

PMID- 23878487
TI  - Primary pulmonary rhabdomyosarcoma in children: Report of three cases with review
      of literature.
AB  - Primary pulmonary rhabdomyosarcoma in children is rare. Three children aged
      three, nine and three years were evaluated for abnormal shadows on radiological
      examination with pneumothorax in two cases. Resection and histopathological
      examination revealed embryonal rhabdomyosarcoma in all and cystic malformation in
      first case. All the three children were treated with surgery and first two
      received adjuvant chemotherapy. The disease free duration was 160 months, 19
      months and seven months respectively. The literature on primary pulmonary
      rhabdomyosarcoma in children was reviewed. 

PMID- 23878488
TI  - Cutaneous metastasis in esophageal squamous cell carcinoma.
AB  - Cutaneous metastasis from internal malignancies are common in breast cancer,
      pulmonary malignancies and melanomas. The primary site of metastases has been
      reported to the chest and abdomen. We are hereby reporting rare case of cutaneous
      metastasis in esophageal cancer. 

PMID- 23878489
TI  - Ovarian stromal tumor with minor sex cord elements with coexistent endometrial
      carcinoma.
AB  - Ovarian stromal tumor with minor sex cord elements is a rare tumor. It is
      composed of predominantly fibrothecomatous tumor with scattered minor sex cord
      elements in less than 10% of the tumor area. These tumors may be hormonally
      active and predispose to carcinoma endometrium. A case of ovarian fibroma-thecoma
      with minor sex cord elements in which coexistent endometrial carcinoma was also
      discovered is being reported. Though thecoma may be a predisposing factor for
      endometrial cancer, meticulous histopathological examination of the ovary may
      reveal additional sources of estrogen like granulosa cell aggregates as in our
      patient. Such patients would require long-term follow-up to detect any recurrence
      of granulosa cell tumor. 

PMID- 23878490
TI  - Microfilariasis of the breast mimicking malignancy.
AB  - We report a 65-year-old female who presented with a 3.5*3 cm retro-areolar lump
      of the right breast with associated right axillary lymphadenopathy, mimicking
      breast cancer. Mammography showed a well-defined mass in the central quadrant of
      the right breast. Fine needle aspiration cytology from the breast lump
      demonstrated many microfilariae of Wuchereria bancrofti. 

PMID- 23878491
TI  - Pattern and determinants of central nervous system relapse in childhood acute
      lymphoblastic leukemia in a resource-limited setting.

PMID- 23878492
TI  - Unsectable cholangiocarcinoma: Additional therapy to chemoradiotherapy.

PMID- 23878493
TI  - Regarding the study testing the addition of gemcitabine to concurrent
      chemoradiotherapy in cervical carcinoma: Clarity needed.

PMID- 23878494
TI  - L-asparaginase-induced cortical vein thrombosis in a child with leukemia: Can we
      rechallenge?

PMID- 23878495
TI  - Antenatal diagnosis of renal tumor: An opportunity lost.

PMID- 23878496
TI  - Docetaxel-induced syndrome of inappropriate antidiuretic hormone secretion.

PMID- 23878498
TI  - Lacrimal gland enlargement in acute myeloid leukemia.

PMID- 23878497
TI  - Is antenatal detection of Wilms tumor a bad prognostic marker.

PMID- 23878499
TI  - Research Challenges and Bioethics Responsibilities in the Aftermath of the
      Presidential Apology to the Survivors of the U. S. Public Health Services
      Syphilis Study at Tuskegee.
AB  - In 1997 President William Clinton issued an apology to the living male survivors
      of the U.S. Public Health Syphilis Study at Tuskegee. While the apology became
      the focus for many, little attention has been paid going forward to two very
      important recommendations by President Clinton that accompanied the apology.
      President Clinton pointed out that it is through the remembering of the shameful
      past of the Syphilis Study at Tuskegee that we can build a better present and a
      better future for the nation. Second, President Clinton directed the Secretary of
      Health and Human Services to work in partnership with higher education to prepare
      training materials for medical researchers as well as postgraduate fellowships to
      train bioethicists to build on core ethical principles of respect for
      individuals, justice, and informed consent, and how to use these principles
      effectively in racial/ethnic minority populations, especially African Americans.
      This article examines bioethical research challenges left in the wake of the U.S.
      Public Health Syphilis Study at Tuskegee and the presidential apology. This
      manuscript raises for consideration the inclusion of these issues in health care
      reform and the implementation of the Affordable Care Act. It asks: What is the
      right or good thing to do? What are our obligations to one another? Two
      challenges are examined: 1) Conducting research with African Americans without
      knowledge of bioethics specific to this population; and 2) The ethical dilemma of
      conducting research that does not adequately take into account the diversity
      within the Black population that is a contributing factor in health disparities.
      Training and policy recommendations responsive to President Clinton's Apology are
      presented.

PMID- 23878500
TI  - Conjunctival HLA-DR and CD8 expression detected by impression cytology in ocular
      graft versus host disease.
AB  - PURPOSE: To assess the expression of human leucocyte antigen (HLA)-DR in
      epithelial cells and cluster of differentiation (CD8)-positive lymphocytes as
      possible markers of chronic ocular graft versus host disease (cGvHD) after
      hematological stem cell transplantation (HSCT). METHODS: Twenty-seven consecutive
      patients with dry-eye symptoms following HSCT (24 [89%] with peripheral blood
      stem cell transplantation and 3 [11%] with bone marrow transplants; 17 [63%]
      familiar allogenic grafts) and 19 age-matched controls were included.
      Conjunctival impression cytology specimens were stained for HLA-DR, cytokeratin
      19, and CD8. Oxford grading scale, blinking frequency, Schirmer test, tear film
      break-up time (TBUT), and Ocular Surface Disease Index (OSDI) were also recorded.
      Wilcoxon nonparametric testing was used to compare controls and HSCT recipients
      and to assess HSCT recipient subgroups with and without clinical cGVHD. RESULTS:
      Eighteen patients showed clinical signs of ocular cGVHD. TBUT and Schirmer test
      scores were significantly lower in patients, while Oxford grades and OSDI were
      significantly higher than in controls. Epithelial HLA-DR expression was generally
      higher in HSCT recipients than in controls, but it did not correlate with ocular
      cGVHD status. CD8-positive lymphocytes were identified in five patients with
      ocular cGvHD and one control. CONCLUSIONS: A strong HLA-DR expression as detected
      by impression cytology appears to indicate a general HSCT response and fails to
      predict ocular cGVHD. However, the detection of CD8-positive lymphocytes using
      impression cytology was frequently associated with ocular cGvHD. Our data warrant
      further evaluation of CD8 expression in impression cytology, along with
      comparison to conjunctival biopsies and brush cytology, as impression cytology
      may offer a less invasive strategy for assessing cGVHD status.

PMID- 23878501
TI  - Lithium chloride promotes host resistance against Pseudomonas aeruginosa
      keratitis.
AB  - PURPOSE: To explore the role of lithium chloride (LiCl) in Pseudomonas aeruginosa
      (PA) keratitis. METHODS: B6 mice were subconjunctivally injected with LiCl in
      contrast to appropriate control sodium chloride (NaCl), and then routinely
      infected with PA. Clinical score, slit-lamp photography, hematoxylin and eosin
      (H&E) staining, and bacterial plate counts were used to determine the role of
      LiCl in PA keratitis. Messenger ribonucleic acid and protein levels of
      inflammatory cytokines in PA-challenged mouse corneas and in vitro cultured
      macrophages and neutrophils were measured with real-time PCR and enzyme-linked
      immunosorbent assay (ELISA), respectively. Apoptosis of the infiltrating
      inflammatory cells in the PA-infected murine corneas was assessed using terminal
      deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end
      labeling staining and propidium iodide staining associated with flow cytometry.
      In cultured murine macrophages and neutrophils, cell apoptosis was determined
      with annexin V/propidium iodide double staining associated with flow cytometry
      and western blot analysis for cleaved caspase-3 and cleaved poly(ADP-ribose)
      polymerase. RESULTS: Treatment with LiCl reduced the severity of corneal disease
      by reducing corneal inflammatory response and bacterial burden. Moreover, LiCl
      increased anti-inflammatory cytokine interleukin-10 levels, decreased
      proinflammatory cytokine tumor necrosis factor-alpha levels, and enhanced
      apoptosis of infiltrating macrophages and neutrophils in the PA-infected mouse
      corneas. In vitro studies further confirmed that LiCl elevated anti-inflammatory
      cytokine expression but reduced proinflammatory cytokine production, as well as
      promoted cell apoptosis in murine macrophages and neutrophils. CONCLUSIONS: This
      study demonstrates a protective role of LiCl in PA keratitis. LiCl promotes host
      resistance against PA infection by suppressing inflammatory responses, enhancing
      inflammatory cell apoptosis, and promoting bacterial clearance.

PMID- 23878502
TI  - Anti-allergic effects of mapracorat, a novel selective glucocorticoid receptor
      agonist, in human conjunctival fibroblasts and epithelial cells.
AB  - PURPOSE: To determine the ocular anti-allergic effects of mapracorat, a novel
      selective glucocorticoid receptor agonist (SEGRA) in primary human conjunctival
      fibroblasts and epithelial cells. METHODS: Two primary human conjunctival cell
      types, human conjunctival epithelial cells (HConEpiC) and human conjunctival
      fibroblasts (HConF), were challenged with interleukin-4 (IL-4) or IL-13 plus
      tumor necrosis factor-alpha (TNF-alpha). Luminex technology was used to profile
      the resulting inflammatory response. The effects of mapracorat on the release of
      eotaxin and regulated on activation, normal T cell expressed and secreted
      (RANTES), two allergy-related chemokines, as well as proinflammatory cytokines
      and intercellular adhesion molecule 1 (ICAM-1) were then determined. Small
      interfering RNA was used to determine whether the effects of mapracorat were
      mediated via the glucocorticoid receptor (GR). Dexamethasone was used as the
      control. RESULTS: IL-13 or IL-4 plus TNF-alpha in the HConF or HConEpiC
      significantly increased eotaxin-1 (HConF only), eotaxin-3, RANTES, multiple
      proinflammatory cytokines, and ICAM-1. Synergistic effects of IL-13 or IL-4 plus
      TNF-alpha were observed in the HConEpiC for RANTES and monocyte chemoattractant
      protein-1, and in the HConF for eotaxin-1, eotaxin-3, and RANTES. Mapracorat
      significantly reduced IL-4 or IL-13 plus TNF-alpha-induced cytokine release and
      ICAM-1 protein in a dose-dependent manner in both cell types, with comparable
      efficacy to dexamethasone. These effects were mediated through the glucocorticoid
      receptor (GR), as demonstrated by the reversal of inhibitory effects after
      silencing of glucocorticoid receptor expression. CONCLUSIONS: Data from these in
      vitro models indicate that mapracorat is efficacious and potent in reducing IL-4
      or IL-13 plus TNF-alpha-induced release of allergy-related and proinflammatory
      cytokines from the HConF and the HConEpiC, supporting clinical evaluation of the
      compound in reducing allergic and inflammatory reactions in allergic
      conjunctivitis.

PMID- 23878503
TI  - Keratoconus corneal architecture after riboflavin/ultraviolet A cross-linking:
      ultrastructural studies.
AB  - PURPOSE: Study to investigate the effects of collagen cross-linking on the
      ultrastructural organization of the corneal stroma in the human keratoconus
      cornea (KC). METHODS: Three normal, three keratoconus (KC1, KC2, KC3), and three
      cross-linked keratoconus (CXL1, CXL2, CXL3) corneas were analyzed. The KC corneas
      were treated with a riboflavin-ultraviolet A (UVA) treatment (CXL) method
      described by Wollensak et al. Penetrating keratoplasty (PKP) was performed 6
      months after treatment. All samples were processed for electron microscopy.
      RESULTS: The riboflavin-UVA-treated CXL corneal stroma showed interlacing
      lamellae in the anterior stroma followed by well-organized parallel running
      lamellae. The lamellae contained uniformly distributed collagen fibrils (CFs)
      decorated with normal proteoglycans (PGs). The CF diameter and interfibrillar
      spacing in the CXL cornea were significantly increased compared to those in the
      KC cornea. The PG area in the CXL corneas were significantly smaller than the PGs
      in the KC cornea. The epithelium and Bowman's layer were also normal. On rare
      occasions, a thick basement membrane and collagenous pannus were also observed.
      CONCLUSIONS: Corneal cross-linking leads to modifications of the cornea stroma.
      The KC corneal structure showed a modification in the CF diameter, interfibrillar
      spacing, and PG area. This resulted in a more uniform distribution of collagen
      fibrils, a key feature for corneal transparency.

PMID- 23878506
TI  - Systematics of Old World Odontacolus Kieffer s.l. (Hymenoptera, Platygastridae
      s.l.): parasitoids of spider eggs.
AB  - The genera Odontacolus Kieffer and Cyphacolus Priesner are among the most
      distinctive platygastroid wasps because of their laterally compressed metasomal
      horn; however, their generic status has remained unclear. We present a
      morphological phylogenetic analysis comprising all 38 Old World and four
      Neotropical Odontacolus species and 13 Cyphacolus species, which demonstrates
      that the latter is monophyletic but nested within a somewhat poorly resolved
      Odontacolus. Based on these results Cyphacolus syn. n. is placed as a junior
      synonym of Odontacolus which is here redefined. The taxonomy of Old World
      Odontacolus s.str. is revised; the previously known species Odontacolus longiceps
      Kieffer (Seychelles), Odontacolus markadicus Veenakumari (India), Odontacolus
      spinosus (Dodd) (Australia) and Odontacolus hackeri (Dodd) (Australia) are re
      described, and 32 new species are described: Odontacolus africanus Valerio &
      Austin sp. n. (Congo, Guinea, Kenya, Madagascar, Mozambique, South Africa,
      Uganda, Zimbabwe), Odontacolus aldrovandii Valerio & Austin sp. n. (Nepal),
      Odontacolus anningae Valerio & Austin sp. n. (Cameroon), Odontacolus
      australiensis Valerio & Austin sp. n. (Australia), Odontacolus baeri Valerio &
      Austin sp. n. (Australia), Odontacolus berryae Valerio & Austin sp. n.
      (Australia, New Zealand, Norfolk Island), Odontacolus bosei Valerio & Austin sp.
      n. (India, Malaysia, Sri Lanka), Odontacolus cardaleae Valerio & Austin sp. n.
      (Australia), Odontacolus darwini Valerio & Austin sp. n. (Thailand), Odontacolus
      dayi Valerio & Austin sp. n. (Indonesia), Odontacolus gallowayi Valerio & Austin
      sp. n. (Australia), Odontacolus gentingensis Valerio & Austin sp. n. (Malaysia),
      Odontacolus guineensis Valerio & Austin sp. n. (Guinea), Odontacolus harveyi
      Valerio & Austin sp. n. (Australia), Odontacolus heratyi Valerio & Austin sp. n.
      (Fiji), Odontacolus heydoni Valerio & Austin sp. n. (Malaysia, Thailand),
      Odontacolus irwini Valerio & Austin sp. n. (Fiji), Odontacolus jacksonae Valerio
      & Austin sp. n. (Cameroon, Guinea, Madagascar), Odontacolus kiau Valerio & Austin
      sp. n. (Papua New Guinea), Odontacolus lamarcki Valerio & Austin sp. n.
      (Thailand), Odontacolus madagascarensis Valerio & Austin sp. n. (Madagascar),
      Odontacolus mayri Valerio & Austin sp. n. (Indonesia, Thailand), Odontacolus mot
      Valerio & Austin sp. n. (India), Odontacolus noyesi Valerio & Austin sp. n.
      (India, Indonesia), Odontacolus pintoi Valerio & Austin sp. n. (Australia, New
      Zealand, Norfolk Island), Odontacolus schlingeri Valerio & Austin sp. n. (Fiji),
      Odontacolus sharkeyi Valerio & Austin sp. n. (Thailand), Odontacolus veroae
      Valerio & Austin sp. n. (Fiji), Odontacolus wallacei Valerio & Austin sp. n.
      (Australia, Indonesia, Malawi, Papua New Guinea), Odontacolus whitfieldi Valerio
      & Austin sp. n. (China, India, Indonesia, Sulawesi, Malaysia, Thailand, Vietnam),
      Odontacolus zborowskii Valerio & Austin sp. n. (Australia), and Odontacolus zimi
      Valerio & Austin sp. n. (Madagascar). In addition, all species of Cyphacolus are
      here transferred to Odontacolus: Odontacolus asheri (Valerio, Masner & Austin)
      comb. n. (Sri Lanka), Odontacolus axfordi (Valerio, Masner & Austin) comb. n.
      (Australia), Odontacolus bhowaliensis (Mani & Mukerjee) comb. n. (India),
      Odontacolus bouceki (Austin & Iqbal) comb. n. (Australia), Odontacolus copelandi
      (Valerio, Masner & Austin) comb. n. (Kenya, Nigeria, Zimbabwe, Thailand),
      Odontacolus diazae (Valerio, Masner & Austin) comb. n. (Kenya), Odontacolus
      harteni (Valerio, Masner & Austin) comb. n. (Yemen, Ivory Coast, Paskistan),
      Odontacolus jenningsi (Valerio, Masner & Austin) comb. n. (Australia),
      Odontacolus leblanci (Valerio, Masner & Austin) comb. n. (Guinea), Odontacolus
      lucianae (Valerio, Masner & Austin) comb. n. (Ivory Coast, Madagascar, South
      Africa, Swaziland, Zimbabwe), Odontacolus normani (Valerio, Masner & Austin)
      comb. n. (India, United Arab Emirates), Odontacolus sallyae (Valerio, Masner &
      Austin) comb. n. (Australia), Odontacolus tessae (Valerio, Masner & Austin) comb.
      n. (Australia), Odontacolus tullyae (Valerio, Masner & Austin) comb. n.
      (Australia), Odontacolus veniprivus (Priesner) comb. n. (Egypt), and Odontacolus
      watshami (Valerio, Masner & Austin) comb. n. (Africa, Madagascar). Two species of
      Odontacolus are transferred to the genus Idris Forster: Idris longispinosus
      (Girault) comb. n. and Idris amoenus (Kononova) comb. n., and Odontacolus doddi
      Austin syn. n. is placed as a junior synonym of Odontacolus spinosus (Dodd).
      Odontacolus markadicus, previously only known from India, is here recorded from
      Brunei, Malaysia, Sri Lanka, Thailand and Vietnam. The relationships,
      distribution and biology of Odontacolus are discussed, and a key is provided to
      identify all species. 

PMID- 23878505
TI  - Novel mutations in RPE65 identified in consanguineous Pakistani families with
      retinal dystrophy.
AB  - PURPOSE: To identify pathogenic mutations responsible for retinal dystrophy in
      three consanguineous Pakistani families. METHODS: A thorough ophthalmic
      examination including fundus examination and electroretinography was performed,
      and blood samples were collected from all participating members. Genomic DNA was
      extracted, and genome-wide linkage and/or exclusion analyses were completed with
      fluorescently labeled short tandem repeat microsatellite markers. Two-point Lod
      scores were calculated, and coding exons along with exon-intron boundaries of
      RPE65 gene were sequenced, bidirectionally. RESULTS: Ophthalmic examinations of
      the patients affected in all three families suggested retinal dystrophy with an
      early, most probably congenital, onset. Genome-wide linkage and/or exclusion
      analyses localized the critical interval in all three families to chromosome 1p31
      harboring RPE65. Bidirectional sequencing of RPE65 identified a splice acceptor
      site variation in intron 2: c.95-1G>A, a single base substitution in exon 3:
      c.179T>C, and a single base deletion in exon 5: c.361delT in the three families,
      respectively. All three variations segregated with the disease phenotype in their
      respective families and were absent from ethnically matched control chromosomes.
      CONCLUSIONS: These results strongly suggest that causal mutations in RPE65 are
      responsible for retinal dystrophy in the affected individuals of these
      consanguineous Pakistani families.

PMID- 23878504
TI  - Diabetes changes expression of genes related to glutamate neurotransmission and
      transport in the Long-Evans rat retina.
AB  - PURPOSE: This study investigated changes in the transcript levels of genes
      related to glutamate neurotransmission and transport as diabetes progresses in
      the Long-Evans rat retina. Transcript levels of vascular endothelial growth
      factor (VEGF), erythropoietin, and insulin-like growth factor binding protein 3
      (IGFBP3) were also measured due to their protective effects on the retinal
      vasculature and neurons. METHODS: Diabetes was induced in Long-Evans rats with a
      single intraperitoneal (IP) injection of streptozotocin (STZ; 65 mg/kg) in sodium
      citrate buffer. Rats with blood glucose >300 mg/dl were deemed diabetic. Age
      matched controls received a single IP injection of sodium citrate buffer only.
      The retinas were dissected at 4 and 12 weeks after induction of diabetes, and
      mRNA and protein were extracted from the left and right retinas of each rat,
      respectively. Gene expression was analyzed using quantitative real-time reverse
      transcription PCR. Enzyme-linked immunosorbent assay was used to quantify the
      concentration of VEGF protein in each retina. Statistical significance was
      determined using 2*2 analysis of variance followed by post-hoc analysis using
      Fisher's protected least squares difference. RESULTS: Transcript levels of two
      ionotropic glutamate receptor subunits and one glutamate transporter increased
      after 4 weeks of diabetes. In contrast, 12 weeks of diabetes decreased the
      transcript levels of several genes, including two glutamate transporters, four
      out of five N-methyl-D-aspartate (NMDA) receptor subunits, and all five kainate
      receptor subunits. Diabetes had a greater effect on gene expression of NMDA and
      kainate receptor subunits than on the alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA) receptor subunits, for which only GRIA4 significantly decreased
      after 12 weeks. VEGF protein levels were significantly increased in 4-week
      diabetic rats compared to age-matched control rats whereas the increase was not
      significant after 12 weeks. Transcript levels of VEGF and VEGF receptors were
      unchanged with diabetes. Erythropoietin and IGFBP3 mRNA levels significantly
      increased at both time points, and IGFBP2 mRNA levels increased after 12 weeks.
      CONCLUSIONS: Diabetes caused significant changes in the transcriptional
      expression of genes related to ionotropic glutamate neurotransmission, especially
      after 12 weeks. Most genes with decreased transcript levels after 12 weeks were
      expressed by retinal ganglion cells, which include glutamate transporters and
      ionotropic glutamate receptors. Two genes expressed by retinal ganglion cells but
      unrelated to glutamate neurotransmission, gamma-synuclein (SNCG) and adenosine A1
      receptor (ADORA1), also had decreased mRNA expression after 12 weeks. These
      findings may indicate ganglion cells were lost as diabetes progressed in the
      retina. Decreased expression of the glutamate transporter SLC1A3 would lead to
      decreased removal of glutamate from the extracellular space, suggesting that
      diabetes impairs this function of Muller cells. These findings suggest that
      ganglion cells were lost due to glutamate excitotoxicity. The changes at 12 weeks
      occurred without significant changes in retinal VEGF protein or mRNA, although
      higher VEGF protein levels at 4 weeks may be an early protective response.
      Increased transcript levels of erythropoietin and IGFBP3 may also be a protective
      response.

PMID- 23878507
TI  - The Collothecidae (Rotifera, Collothecacea) of Thailand, with the description of
      a new species and an illustrated key to the Southeast Asian fauna.
AB  - Following previous reports indicating a remarkable high diversity of sessile
      rotifers in Southeast Asian freshwaters, we report on an extensive study of the
      diversity of Collothecidae rotifers from fifteen freshwater habitats in Thailand.
      A total of 13 species, including two additional infraspecific variants, of
      Collothecidae are recorded, one of which is described as a new species of
      Collotheca. We further add taxonomic remarks on some of the taxa on record and
      illustrate the uncinate trophi of several representatives by scanning electron
      microscopic images. Finally, we provide illustrated identification keys to the
      Collothecidae recorded to date from Southeast Asia. 

PMID- 23878508
TI  - Western Hemisphere Zuphiini: descriptions of Coarazuphium whiteheadi, new
      species, and Zuphioides, new genus, and classification of the genera (Coleoptera,
      Carabidae).
AB  - Based on small samples (exemplars) analyzed with morphological methods, including
      detailed descriptions and illustrations, this study treats primarily the Zuphium
      genus-group in the Western Hemisphere, which comprises two precinctive genera:
      Coarazuphium Gnaspini, Vanin & Godoy, 1998 (type species Parazuphium tessai Godoy
      & Vanin, 1990) and Zuphioides gen. n. (type species Zuphium mexicanum Chaudoir,
      1863). The genus Coarazuphium includes six troglobitic species from Brazilian
      caves, and one probably hypogaeic (troglophilic) species from the mountains of
      Oaxaca, in Mexico (Coarazuphium whiteheadi, sp. n., type locality, ridge top, in
      western Oaxaca, Mexico, at 2164 m, 35 km north of San Pedro Juchatengo, 16.462N,
      97.010W). The epigaeic genus Zuphioides includes 23 species, with its
      geographical range extended from Neotropical temperate Argentina in southern
      South America, northward through the tropics to north temperate southeastern
      Canada, in the Nearctic Region. Keys are provided to the species of Coarazuphium
      and to thegenera of Western Hemisphere Zuphiini. 

PMID- 23878509
TI  - Circumpolar dataset of sequenced specimens of Promachocrinus kerguelensis
      (Echinodermata, Crinoidea).
AB  - This circumpolar dataset of the comatulid (Echinodermata: Crinoidea)
      Promachocrinus kerguelensis (Carpenter, 1888) from the Southern Ocean, documents
      biodiversity associated with the specimens sequenced in Hemery et al. (2012). The
      aim of Hemery et al. (2012) paper was to use phylogeographic and phylogenetic
      tools to assess the genetic diversity, demographic history and evolutionary
      relationships of this very common and abundant comatulid, in the context of the
      glacial history of the Antarctic and Sub-Antarctic shelves (Thatje et al. 2005,
      2008). Over one thousand three hundred specimens (1307) used in this study were
      collected during seventeen cruises from 1996 to 2010, in eight regions of the
      Southern Ocean: Kerguelen Plateau, Davis Sea, Dumont d'Urville Sea, Ross Sea,
      Amundsen Sea, West Antarctic Peninsula, East Weddell Sea and Scotia Arc including
      the tip of the Antarctic Peninsula and the Bransfield Strait. We give here the
      metadata of this dataset, which lists sampling sources (cruise ID, ship name,
      sampling date, sampling gear), sampling sites (station, geographic coordinates,
      depth) and genetic data (phylogroup, haplotype, sequence ID) for each of the 1307
      specimens. The identification of the specimens was controlled by an expert
      taxonomist specialist of crinoids (Marc Eleaume, Museum national d'Histoire
      naturelle, Paris) and all the COI sequences were matched against those available
      on the Barcode of Life Data System (BOLD:
      http://www.boldsystems.org/index.php/IDS_OpenIdEngine). This dataset can be used
      by studies dealing with, among other interests, Antarctic and/or crinoid
      diversity (species richness, distribution patterns), biogeography or habitat /
      ecological niche modeling. This dataset is accessible through the GBIF network at
      http://ipt.biodiversity.aq/resource.do?r=proke. 

PMID- 23878510
TI  - Pareiorhina hyptiorhachis, a new catfish species from Rio Paraiba do Sul basin,
      southeastern Brazil (Siluriformes, Loricariidae).
AB  - Pareiorhina hyptiorhachis is described from Ribeirao Fernandes and Rio Pomba, Rio
      Paraiba do Sul basin, Brazil. The new species is distinguished from its congeners
      (Pareiorhina brachyrhyncha, Pareiorhina carrancas, Pareiorhina cepta, and
      Pareiorhina rudolphi) by the presence of a conspicuous ridge on the trunk
      posterior to the dorsal fin (postdorsal ridge), simple teeth, a completely naked
      abdomen, a round dorsal profile of the head, greater suborbital depth and greater
      head width. We discuss the distributional pattern of the new species and its
      congeners and hypothesize that headwater capture is responsible for the
      distribution of Pareiorhina species across different watersheds in southeastern
      of Brazil. 

PMID- 23878511
TI  - Neogosseidae (Gastrotricha, Chaetonotida) from the iSimangaliso Wetland Park,
      KwaZulu-Natal, South Africa.
AB  - Among the mostly benthic gastrotrichs, the Neogosseidae (Gastrotricha,
      Chaetonotida) are particularly interesting from an evolutionary point of view in
      virtue of their planktonic lifestyle; yet, they are poorly known and
      uncertainties concerning morphological traits hamper accurate in-group
      systematics. During a recent survey of meiofauna in the iSimangaliso Wetland
      Park, South Africa, two species of Neogosseidae were found in a freshwater pond
      near Charter's Creek on the Western Shores of Lake St Lucia. Based on
      morphological traits, one species has been identified as Neogossea acanthocolla,
      originally described from Brazil, while the other, affiliated to the genus
      Kijanebalola, is proposed as new to science. Using a combination of differential
      interference contrast and scanning electron microscopy, fine anatomical details
      were observed and are here discussed in a larger taxonomic framework, especially
      regarding Kijanebalola devestiva sp. n. Results have also provided reasons for a
      revision of the diagnostic traits of Kijanebalola, Neogossea and the whole Family
      Neogosseidae. Besides expanding awareness about the biodiversity hosted by South
      Africa's first UNESCO World Heritage Site, our study will be beneficial to future
      phylogenetic studies of the Gastrotricha based on morphology, by allowing the
      selection and/or a more precise character coding of traits of phylogenetic
      relevance. 

PMID- 23878512
TI  - History of tachinid classification (Diptera, Tachinidae).
AB  - The history of the classification of the Tachinidae (Diptera) is traced from
      Meigen to the present. The contributions of Robineau-Desvoidy, Townsend,
      Villeneuve, Mesnil, Herting, Wood and many others are discussed within a
      chronological, taxonomic, and geographic context. The gradual development of the
      Tachinidae into its modern concept as a family of the Oestroidea and the
      emergence of the classificatory scheme of tribes and subfamilies in use today are
      reviewed. Certain taxa that have in the past been difficult to place, or continue
      to be of uncertain affinity, are considered and some are given in a table to show
      their varied historical treatments. The more significant systematic works
      published on the Tachinidae in recent decades are enumerated chronologically. 

PMID- 23878513
TI  - Description of Caurinus tlagu, new species, from Prince of Wales Island, Alaska
      (Mecoptera, Boreidae, Caurininae).
AB  - A new species of the cryptic, minute, wingless, and enigmatic taxon Caurinus, and
      the second for the subfamily Caurininae,is described from Prince of Wales Island
      in the Alexander Archipelago, Alaska. It is distinguished from its only congener,
      Caurinus dectes Russell, 1979b, which occurs 1,059 km southeast in Oregon and
      Washington, based on external morphology and sequences of the mitochondrial gene
      cytochrome oxidase II. These two species are probably evolutionary relicts - the
      only known members of a clade dating to the Late Jurassic or older. 

PMID- 23878514
TI  - A tropical Atlantic species of Melibe Rang, 1829 (Mollusca, Nudibranchia,
      Tethyiidae).
AB  - A new species of Melibe is described based on two specimens collected in Florida.
      This new species is well differentiated morphologically and genetically from
      other species of Melibe studied to date. The four residue deletions in the
      cytochrome c oxidase subunit 1 protein found in all previously sequenced tropical
      species of Melibe sequenced (and Melibe rosea) are also present in this new
      species. These deletions do not appear to affect important structural components
      of this protein but might have fitness implications. This paper provides the
      first confirmed record of Melibe in the tropical western Atlantic Ocean. 

PMID- 23878515
TI  - Where's Waldo? A new commensal species, Waldo arthuri (Mollusca, Bivalvia,
      Galeommatidae), from the Northeastern Pacific Ocean.
AB  - A galeommatid bivalve mollusk, representing a new species, is described from off
      the coasts of California and Vancouver Island, British Columbia. The new bivalve
      has a commensal relationship with the heart urchin, Brisaster latifrons. It has
      been observed crawling between the oral spines of this urchin, frequently near
      the peristome. The bivalve has been recorded from 80 (Vancouver Island) to 444
      (southern California) meters depth, in muddy sediments. In common with other
      galeommatoideans, the new species broods its young; however it differs from the
      large majority of commensal members in lacking planktotrophic larval development.
      Waldo arthuri, new species, has multiple morphological, ecological and
      developmental similarities to other members of the genus Waldo Nicol, 1966, from
      the southern Atlantic and Antarctic Oceans. This is most pronounced for the
      Argentine species, Waldo paucitentaculatus Zelaya & Ituarte, 2013, Waldo
      arthuri's sister speciesin nuclear and mitochondrial gene trees. Despite this
      close relationship, Waldo arthuri is phylogentically distinct and possesses
      several hinge, shell sculpture, foot, and mantle tentacle characteristics that
      merit its description as new. 

PMID- 23878516
TI  - New species of Brachystomellidae and characterization of Micronella porcus
      (Denis, 1933) from Brazil.
AB  - Three new species of Brachystomellidae from high altitude fields of southeast
      Brazil are described and illustrated and additions made to the description of
      Micronella porcus (Denis, 1933). The new species are Neorganella rotundatae sp.
      n., the second for the genus, Micronella itacaman sp. n. and Micronella
      longisensilla sp. n. Diagnosis of the genera have been extended. An
      identification key to the genus Micronella Arle, 1959 is provided. 

PMID- 23878517
TI  - Characterization of Lesion Formation and Bubble Activities during High Intensity
      Focused Ultrasound Ablation using Temperature-Derived Parameters.
AB  - Successful high-intensity focused ultrasound (HIFU) thermal tissue ablation
      relies on accurate information of the tissue temperature and tissue status. Often
      temperature measurements are used to predict and monitor the ablation process. In
      this study, we conducted HIFU ablation experiments with ex vivo porcine
      myocardium tissue specimens to identify changes in temperature associated with
      tissue coagulation and bubble/cavity formation. Using infrared (IR) thermography
      and synchronized bright-field imaging with HIFU applied near the tissue surface,
      parameters derived from the spatiotemporal evolution of temperature were
      correlated with HIFU-induced lesion formation and overheating, of which the
      latter typically results in cavity generation and/or tissue dehydration.
      Emissivity of porcine myocardium was first measured to be 0.857 +/- 0.006 (n =
      3). HIFU outcomes were classified into non-ablative, normal lesion, and
      overheated lesion. A marked increase in the rate of temperature change during
      HIFU application was observed with lesion formation. A criterion using the
      maximum normalized second time derivative of temperature change provided 99.1%
      accuracy for lesion identification with a 0.05 s-1 threshold. Asymmetric
      temperature distribution on the tissue surface was observed to correlate with
      overheating and/or bubble generation. A criterion using the maximum displacement
      of the spatial location of the peak temperature provided 90.9% accuracy to
      identify overheated lesion with a 0.16 mm threshold. Spatiotemporal evolution of
      temperature obtained using IR imaging allowed determination of the cumulative
      equivalent minutes at 43  degrees C (CEM43) for lesion formation to be 170 min.
      Similar temperature characteristics indicative of lesion formation and
      overheating were identified for subsurface HIFU ablation. These results suggest
      that parameters derived from temperature changes during HIFU application are
      associated with irreversible changes in tissue and may provide useful information
      for monitoring HIFU treatment.

PMID- 23878519
TI  - Self Views of African American Youth are Related to the Gender Stereotypes and
      Academic Attributions of Their Mothers.
AB  - We examined relations among African American mothers' (N = 392) stereotypes about
      gender differences in mathematics, science, and reading performance, parents'
      attributions about their children's academic successes and failures, and their
      seventh and eighth grade children's academic self-views (domain-specific ability
      attributions and self-concept). Parents' stereotypes about gender differences in
      abilities were related to their ability attributions for their children's
      successes and failures within academic domains. Mothers' attributions, in turn,
      were related to children's attributions, particularly among girls. Mothers'
      attributions of their children's successes to domain-specific ability were
      related to the self-concepts of daughters, and failure attributions were related
      to domain-specific self-concepts of sons. The influences of parents' beliefs on
      young adolescents' identity beliefs are discussed.

PMID- 23878518
TI  - Violence risk: re-defining variables from the first-person perspective.
AB  - Over the past 25 years, there have been notable advances in violence risk
      assessment of mentally ill individuals using actuarial methods to define high
      versus low risk groups. A focus on readily observable risk factors, however, has
      led to a relative neglect of how the offender's subjective states may be valuable
      to consider in research on the ongoing assessment and prevention of violence. We
      argue for the relevance of considering idiographic features of subjective
      experience in the development of structured assessment methods. We then identify
      three heuristic groups of existing constructs related to aggressive and illegal
      behavior that may capture modifiable, time-varying aspects of mental functioning
      leading up to involvement in an act of violence. These hypothesized domains are:
      (i) construal of intent and cause; (ii) normative reference points; and (iii)
      emotion recognition and regulation. We suggest that risk state for violence can
      be studied in a parsimonious and direct manner through systematic research on
      coded speech samples. The coding method for such an assessment procedure would be
      almost identical to existing structured clinical judgment instruments with the
      difference that variables be defined from a first-person point of view. Some
      implications of this approach for the tertiary prevention of violence in high
      risk individuals are described.

PMID- 23878520
TI  - Personalized lifestyle medicine: relevance for nutrition and lifestyle
      recommendations.
AB  - Public health recommendations for lifestyle modification, including diet and
      physical activity, have been widely disseminated for the prevention and treatment
      of disease. These guidelines are intended for the overall population without
      significant consideration for the individual with respect to one's genes and
      environment. Personalized lifestyle medicine is a newly developed term that
      refers to an approach to medicine in which an individual's health metrics from
      point-of-care diagnostics are used to develop lifestyle medicine-oriented
      therapeutic strategies for improving individual health outcomes in managing
      chronic disease. Examples of the application of personalized lifestyle medicine
      to patient care include the identification of genetic variants through laboratory
      tests and/or functional biomarkers for the purpose of designing patient-specific
      prescriptions for diet, exercise, stress, and environment. Personalized lifestyle
      medicine can provide solutions to chronic health problems by harnessing
      innovative and evolving technologies based on recent discoveries in genomics,
      epigenetics, systems biology, life and behavioral sciences, and diagnostics and
      clinical medicine. A comprehensive, personalized approach to medicine is required
      to promote the safety of therapeutics and reduce the cost of chronic disease.
      Personalized lifestyle medicine may provide a novel means of addressing a
      patient's health by empowering them with information they need to regain control
      of their health. 

PMID- 23878521
TI  - A case study on stratified settlement and rebound characteristics due to
      dewatering in Shanghai subway station.
AB  - Based on the Yishan Metro Station Project of Shanghai Metro Line number 9, a
      centrifugal model test was conducted to investigate the behavior of stratified
      settlement and rebound (SSR) of Shanghai soft clay caused by dewatering in deep
      subway station pit. The soil model was composed of three layers, and the
      dewatering process was simulated by self-invention of decompressing devise. The
      results indicate that SSR occurs when the decompression was carried out, and only
      negative rebound was found in sandy clay, but both positive and negative rebound
      occurred in the silty clay, and the absolute value of rebound in sandy clay was
      larger than in silty clay, and the mechanism of SSR was discussed with mechanical
      sandwich model, and it was found that the load and cohesive force of different
      soils was the main source of different responses when decompressed. 

PMID- 23878524
TI  - Estimation of recurrence interval of large earthquakes on the central Longmen
      Shan fault zone based on seismic moment accumulation/release model.
AB  - Recurrence interval of large earthquake on an active fault zone is an important
      parameter in assessing seismic hazard. The 2008 Wenchuan earthquake (Mw 7.9)
      occurred on the central Longmen Shan fault zone and ruptured the Yingxiu-Beichuan
      fault (YBF) and the Guanxian-Jiangyou fault (GJF). However, there is a
      considerable discrepancy among recurrence intervals of large earthquake in
      preseismic and postseismic estimates based on slip rate and paleoseismologic
      results. Post-seismic trenches showed that the central Longmen Shan fault zone
      probably undertakes an event similar to the 2008 quake, suggesting a
      characteristic earthquake model. In this paper, we use the published seismogenic
      model of the 2008 earthquake based on Global Positioning System (GPS) and
      Interferometric Synthetic Aperture Radar (InSAR) data and construct a
      characteristic seismic moment accumulation/release model to estimate recurrence
      interval of large earthquakes on the central Longmen Shan fault zone. Our results
      show that the seismogenic zone accommodates a moment rate of (2.7 +/- 0.3) * 1017
      N m/yr, and a recurrence interval of 3900 +/- 400 yrs is necessary for
      accumulation of strain energy equivalent to the 2008 earthquake. This study
      provides a preferred interval estimation of large earthquakes for seismic hazard
      analysis in the Longmen Shan region.

PMID- 23878523
TI  - Chrysanthemum cutting productivity and rooting ability are improved by grafting.
AB  - Chrysanthemum has been commercially propagated by rooting of cuttings, whereas
      the quality will decline over multiple collections from a single plant.
      Therefore, we compared the vigour, rooting ability, and some physiological
      parameters between cuttings harvested from nongrafted "Jinba" (non-grafted
      cuttings) with those collected from grafted "Jinba" plants onto Artemisia
      scoparia as a rootstock (grafted cuttings). The yield, length, node number, stem
      diameter, fresh weight, and dry weight of the grafted cuttings were superior to
      the non-grafted cuttings. Also grafted cuttings "Jinba" rooted 1 day earlier, but
      showing enhanced rooting quality including number, length, diameter, and dry
      weight of roots, where compared to the non-grafted. The physiological parameters
      that indicated contents of soluble protein, peroxidase activity, soluble sugar,
      and starch, ratios of soluble sugar/nitrogen ratio, and carbohydrate/nitrogen
      (C/N), as well as contents of indole-3-acetic acid (IAA) and abscisic acid (ABA),
      and IAA/ABA ratio were significantly increased in the grafted cuttings. This
      suggested their important parts in mediating rooting ability. Results from this
      study showed that grafting improved productivity and rooting ability related to
      an altered physiology, which provide a means to meet the increasing demand. 

PMID- 23878522
TI  - Natural antisense transcripts in plants: a review and identification in soybean
      infected with Phakopsora pachyrhizi SuperSAGE library.
AB  - Natural antisense ranscripts (NAT) are RNA molecules complementary to other
      endogenous RNAs. They are capable of regulating the expression of target genes at
      different levels (transcription, mRNA stability, translation, etc.). Such a
      property makes them ideal for interventions in organisms' metabolism. The present
      study reviewed plant NAT aspects, including features, availability and genesis,
      conservation and distribution, coding capacity, NAT pair expression, and
      functions. Besides, an in silico identification of NATs pairs was presented,
      using deepSuperSAGE libraries of soybean infected or not with Phakopsora
      pachyrhizi. Results showed that around 1/3 of the 77,903 predicted trans-NATs (by
      PlantsNATsDB database) detected had unitags mapped in both sequences of each
      pair. The same 1/3 of the 436 foreseen cis-NATs showed unitags anchored in both
      sequences of the related pairs. For those unitags mapped in NAT pairs, a
      modulation expression was assigned as upregulated, downregulated, or
      constitutive, based on the statistical analysis (P < 0.05). As a result, the
      infected treatment promoted the expression of 2,313 trans-NATs pairs comprising
      unitags exclusively from that library (1,326 pairs had unitags only found in the
      mock library). To understand the regulation of these NAT pairs could be a key
      aspect in the ASR plant response. 

PMID- 23878525
TI  - Determination of interesting toxicological elements in PM2.5 by neutron and
      photon activation analysis.
AB  - Human activities introduce compounds increasing levels of many dangerous species
      for environment and population. In this way, trace elements in airborne
      particulate have a preeminent position due to toxic element presence affecting
      the biological systems. The main problem is the analytical determination of such
      species at ultratrace levels: a very specific methodology is necessary with
      regard to the accuracy and precision and contamination problems. Instrumental
      Neutron Activation Analysis and Instrumental Photon Activation Analysis assure
      these requirements. A retrospective element analysis in airborne particulate
      collected in the last 4 decades has been carried out for studying their trend.
      The samples were collected in urban location in order to determine only effects
      due to global aerosol circulation; semiannual samples have been used to
      characterize the summer/winter behavior of natural and artificial origin. The
      levels of natural origin element are higher than those in other countries owing
      to geological and meteorological factors peculiar to Central Italy. The levels of
      artificial elements are sometimes less than those in other countries, suggesting
      a less polluted general situation for Central Italy. However, for a few elements
      (e.g., Pb) the levels measured are only slight lower than those proposed as air
      ambient standard.

PMID- 23878526
TI  - Sample training based wildfire segmentation by 2D histogram theta-division with
      minimum error.
AB  - A novel wildfire segmentation algorithm is proposed with the help of sample
      training based 2D histogram theta-division and minimum error. Based on minimum
      error principle and 2D color histogram, the theta-division methods were presented
      recently, but application of prior knowledge on them has not been explored. For
      the specific problem of wildfire segmentation, we collect sample images with
      manually labeled fire pixels. Then we define the probability function of error
      division to evaluate theta-division segmentations, and the optimal angle theta is
      determined by sample training. Performances in different color channels are
      compared, and the suitable channel is selected. To further improve the accuracy,
      the combination approach is presented with both theta-division and other
      segmentation methods such as GMM. Our approach is tested on real images, and the
      experiments prove its efficiency for wildfire segmentation. 

PMID- 23878527
TI  - Small obstacle avoidance sensor.
AB  - This paper describes a laser ranging sensor that is suitable for applications
      like small unmanned aerial vehicles. The hardware consists of a diode emitter
      array and line-scan charge coupled devices. A structured-light technique measures
      ranges up to 30 meters for 64 field angles in a 90 degree field of view.
      Operation is eye safe, and the laser wavelength is not visible to night vision
      goggles. This paper describes a specific sensor design in order to illustrate
      performance for a given package size. 

PMID- 23878528
TI  - Effects of thermal mass, window size, and night-time ventilation on peak indoor
      air temperature in the warm-humid climate of Ghana.
AB  - Most office buildings in the warm-humid sub-Saharan countries experience high
      cooling load because of the predominant use of sandcrete blocks which are of low
      thermal mass in construction and extensive use of glazing. Relatively, low night
      time temperatures are not harnessed in cooling buildings because office openings
      remain closed after work hours. An optimization was performed through a
      sensitivity analysis-based simulation, using the Energy Plus (E+) simulation
      software to assess the effects of thermal mass, window size, and night
      ventilation on peak indoor air temperature (PIAT). An experimental system was
      designed based on the features of the most promising simulation model,
      constructed and monitored, and the experimental data used to validate the
      simulation model. The results show that an optimization of thermal mass and
      window size coupled with activation of night-time ventilation provides a
      synergistic effect to obtain reduced peak indoor air temperature. An expression
      that predicts, indoor maximum temperature has been derived for models of various
      thermal masses. 

PMID- 23878529
TI  - Transverse carpal ligament and forearm fascia release for the treatment of carpal
      tunnel syndrome change the entrance angle of flexor tendons to the A1 pulley: the
      relationship between carpal tunnel surgery and trigger finger occurrence.
AB  - PURPOSE: The appearance of trigger finger after decompression of the carpal
      tunnel without a preexisting symptom has been reported in a few articles.
      Although, the cause is not clear yet, the loss of pulley action of the transverse
      carpal ligament has been accused mostly. In this study, we planned a
      biomechanical approach to fresh cadavers. METHODS: The study was performed on 10
      fresh amputees of the arm. The angles were measured with (1) the transverse
      carpal ligament and the distal forearm fascia intact, (2) only the transverse
      carpal ligament incised, (3) the distal forearm fascia incised to the point 3 cm
      proximal from the most proximal part of the transverse carpal ligament in
      addition to the transverse carpal ligament. The changes between the angles
      produced at all three conditions were compared to each other. RESULTS: We saw
      that the entrance angle increased in all of five fingers in an increasing manner
      from procedure 1 to 3, and it was seen that the maximal increase is detected in
      the middle finger from procedure 1 to procedure 2 and the minimal increase is
      detected in little finger. DISCUSSION: Our results support that transverse carpal
      ligament and forearm fascia release may be a predisposing factor for the
      development of trigger finger by the effect of changing the enterance angle to
      the A1 pulley and consequently increase the friction in this anatomic area.
      CLINICAL RELEVANCE: This study is a cadaveric study which is directly
      investigating the effect of a transverse carpal ligament release on the enterance
      angle of flexor tendons to A1 pulleys in the hand.

PMID- 23878530
TI  - Phase stability and site preference of Tb-Fe-Co-V compounds.
AB  - The effect of cobalt on the structural properties of intermetallic Tb3Fe(27.4
      x)Co(x)V1.6 with Nd3(Fe,Ti)29 structure has been studied by using interatomic
      pair potentials obtained through the lattice inversion method. Calculated results
      show that the preferential occupation site of the V atom is found to be the
      4i(Fe3) site, and Fe atoms are substituted for Co atoms with a strong preference
      for the 8j(Fe8) site. The calculated lattice constants coincide quite well with
      experimental values. The calculated crystal structure can recover after either an
      overall wide-range macrodeformation or atomic random motion, demonstrating that
      this system has the stable structure of Nd3(Fe,Ti)29. All these prove the
      effectiveness of interatomic pair potentials obtained through the lattice
      inversion method in the description of rare-earth materials.

PMID- 23878531
TI  - Transapical approach for mitral valve repair during insertion of a left
      ventricular assist device.
AB  - BACKGROUND: Severe mitral regurgitation (MR) is common in patients who are
      undergoing insertion of a left ventricular assist device (LVAD). This study
      analyzes the outcomes of a transapical approach for edge-to-edge repair of the
      mitral valve during insertion of a left ventricular assist device in 19 patients
      with MR. METHODS: This retrospective study includes 19 patients who were
      implanted between March 21, 2011, and August 31, 2011, at the University of
      Chicago. Clinical data include preoperative ejection fraction, post- and
      preoperative pulmonary arterial pressures, cardiopulmonary bypass time, post- and
      preoperative mitral regurgitation severity, endotracheal CO2, and LVAD pulse
      index. RESULTS: All of the 19 patients had a reduction in mitral regurgitation.
      Fourteen of the 19 patients had at least a three-point reduction in MR severity.
      The average postoperative pulmonary arterial pressure (PAP) decreased after the
      surgical procedure from 44/22 +/- 14/5 mmHg to 57/28 +/- 9/5 mmHg. Average CPB
      time was 128 +/- 27 minutes. Average length-of-stay (LOS) was 21 +/- 10 days.
      CONCLUSIONS: Concomitant MV repair using a transapical approach is advantageous
      for this small cohort of patients. The surgical procedure is less complex and has
      a shorter CPB time and LOS, and all of the patients demonstrated significant
      improvement in postoperative MR and moderate improvement in PAP.

PMID- 23878532
TI  - Novel imaging enhancements in capsule endoscopy.
AB  - Video capsule endoscopy that was launched 10 years ago has become a first-line
      procedure for examining the small bowel. The most common indications for capsule
      endoscopy are obscure gastrointestinal bleeding, Crohn's disease, polyposis
      syndromes, and evaluation of patients with complicated celiac disease. The ideal
      capsule should improve the quality of the image and have a faster frame rate than
      the currently available one. There should be a therapeutic capsule capable of
      performing a biopsy, aspirating fluid, delivering drugs, and measuring the
      motility of the small bowel wall. Another major leap forward would be the
      capability of remote control of capsule's movement in order to navigate it to
      reach designated anatomical areas for carrying out a variety of therapeutic
      options. Technology for improving the capability of the future generation
      capsules almost within grasp and it would not be surprising to witness the
      realization of these giant steps within the coming decade. In this review we will
      focus on the current clinical applications of capsule endoscopy for imaging of
      the small bowel and colon and will additionally give an outlook on future
      concepts and developments of capsule endoscopy. 

PMID- 23878535
TI  - Does the site of anterior tracheal puncture affect the success rate of retrograde
      intubation? A prospective, manikin-based study.
AB  - Background. Retrograde intubation is useful for obtaining endotracheal access
      when direct laryngoscopy proves difficult. The technique is a practical option in
      the "cannot intubate / can ventilate" scenario. However, it is equally useful as
      an elective technique in awake patients with anticipated difficult airways. Many
      practitioners report difficulty successfully advancing the endotracheal tube due
      to anatomical obstructions and the acute angle of the anterograde guide. The
      purpose of this study was to test whether a more caudal tracheal puncture would
      increase the success rate. Methods. Twenty-four anesthesiology residents were
      randomly assigned to either a cricothyroid or a cricotracheal puncture group.
      Each was instructed how to perform the technique and then attempted it on a
      manikin at their assigned site. Data collection included whether the trachea was
      intubated, the number of attempts required, and the total time. Results. Both
      groups displayed a high degree of success. While the group assigned to the
      cricotracheal site required significantly more time to perform the procedure,
      they accomplished it in fewer attempts than the cricothyroid group. Conclusion.
      Retrograde intubation performed via a cricotracheal puncture site, while more
      time consuming, resulted in fewer attempts to advance the endotracheal tube and
      may reduce in vivo laryngeal trauma. 

PMID- 23878533
TI  - Pharmacological therapy of gastroesophageal reflux in preterm infants.
AB  - Although gastroesophageal reflux (GER) is a very common phenomenon among preterm
      infants, its therapeutic management is still an issue of debate among
      neonatologists. A step-wise approach should be advisable, firstly promoting
      nonpharmacological interventions and limiting drugs to selected infants
      unresponsive to the conservative measures or who are suffering from severe GER
      with clinical complications. Despite of this, a concerning pharmacological
      overtreatment has been increasingly reported. Most of the antireflux drugs,
      however, have not been specifically assessed in preterm infants; moreover,
      serious adverse effects have been noticed in association to their administration.
      This review mainly aims to draw the state of the art regarding the
      pharmacological management of GER in preterm infants, analyzing the best piecies
      of evidence currently available on the most prescribed anti-reflux drugs.
      Although further trials are required, sodium alginate-based formulations might be
      considered promising; however, data regarding their safety are still limited. Few
      piecies of evidence on the efficacy of histamine-2 receptor blockers and proton
      pump inhibitors in preterm infants with GER are currently available.
      Nevertheless, a significantly increased risk of necrotizing enterocolitis and
      infections has been largely reported in association with their use, thereby
      leading to an unfavorable risk-benefit ratio. The efficacy of metoclopramide in
      GER's improvement still needs to be clarified. Other prokinetic agents, such as
      domperidone and erythromycin, have been reported to be ineffective, whereas
      cisapride has been withdrawn due to its remarkable cardiac adverse effects. 

PMID- 23878536
TI  - Factors influencing quality of life for disabled and nondisabled elderly
      population: the results of a multiple correspondence analysis.
AB  - Objectives. The aim of our study is to examine the role of some factors
      (sociodemographic patterns, social relationship support, and trust in healthcare
      actors) on structure of quality of life among the Italian elderly population, by
      stratifying according to presence or absence of disability. Methods. Using data
      of the Italian National Institute of Statistics (ISTAT) survey, we obtained a
      sample of 25,183 Italian people aged 65+ years. Multiple Correspondence Analysis
      (MCA) was used to test such a relationship. Results. By applying the MCA between
      disabled and nondisabled elderly population, we identified three dimensions:
      "demographic structure and social contacts," "social relationships," "trust in
      the Italian National Health Services (INHS)." Furthermore, the difference in
      trust on the INHS and its actors was seen among disabled and non-disabled elderly
      population. Conclusions. Knowledge on the concept of quality of life and its
      application to the elderly population either with or without disability should
      make a difference in both people's life and policies and practices affecting
      life. New domains, such as information and trusting relationships both within and
      towards the care network's nodes, are likely to play an important role in this
      relationship. 

PMID- 23878534
TI  - Current pharmacological management of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD), a common disorder with troublesome
      symptoms caused by reflux of gastric contents into the esophagus, has adverse
      impact on quality of life. A variety of medications have been used in GERD
      treatment, and acid suppression therapy is the mainstay of treatment for GERD.
      Although proton pump inhibitor is the most potent acid suppressant and provides
      good efficacy in esophagitis healing and symptom relief, about one-third of
      patients with GERD still have persistent symptoms with poor response to standard
      dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and
      prokinetic agents are usually used as add-on therapy to PPI in clinical practice.
      Development of novel therapeutic agents has focused on the underlying mechanisms
      of GERD, such as transient lower esophageal sphincter relaxation, motility
      disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations
      of PPI with faster and longer duration of action and potassium-competitive acid
      blocker, a newer acid suppressant, have also been investigated in clinical
      trials. In this review, we summarize the current and developing therapeutic
      agents for GERD treatment. 

PMID- 23878537
TI  - B-flow twinkling sign in preoperative evaluation of cervical lymph nodes in
      patients with papillary thyroid carcinoma.
AB  - Papillary thyroid cancer (PTC) is the most common histologic type of
      differentiated thyroid cancer. The first site of metastasis is the cervical lymph
      nodes (LNs). The ultrasonography (US) is the best diagnostic method for the
      detection of cervical metastatic LNs. We use a new technique, B-flow imaging
      (BFI), recently used for evaluation of thyroid nodules, to estimate the presence
      of BFI twinkling signs (BFI-TS), within metastatic LNs in patients with PTC. Two
      hundred and fifty-two patients with known PTC were examined for preoperative
      evaluation with conventional US and BFI. Only 83 with at least one metastatic LN
      were included. All patients included underwent surgery; the final diagnosis was
      based on the results of histology. The following LN characteristics were
      evaluated: shape, abnormal echogenicity, absent hilum, calcifications, cystic
      appearance, peripheral vascularization, and BFI-TS. A total of 604 LNs were
      analyzed. Of these, 298 were metastatic, according to histopathology. The BFI-TS
      showed high values of specificity (99.7%) and sensitivity (80.9%). The
      combination of each conventional US sign with the BF-TS increases the
      specificity. Our findings suggest that BFI can be helpful in the selection of
      suspicious neck LNs that should be examined at cytologic examination for accurate
      preoperative staging and individual therapy selection. 

PMID- 23878538
TI  - Inflammatory Markers: C-Reactive Protein, Erythrocyte Sedimentation Rate, and
      Leukocyte Count in Vitamin D Deficient Patients with and without Chronic Kidney
      Disease.
AB  - Although some studies revealed a positive relationship between vitamin D3
      deficiency and inflammatory markers, there have been also many studies that
      failed to find this relationship. The aim of this large scaled study is to
      determine the association between the level of plasma 25 hydroxy vitamin D3 [25
      (OH) D3] and inflammatory markers in the general population without chronic
      kidney disease (CKD) and in patients with CKD. Participants with simultaneously
      measured inflammatory markers and 25-(OH) D3 levels were retrospectively analyzed
      (n = 1897). The incidence of all-cause inflammation infection, hospitalization,
      chronic renal failure, and vitamin B12 deficiency was evaluated. The medians of
      serum creatinine levels in subjects without renal failure were lower in 25-(OH)
      D3 deficient group. Patients with CKD were more likely to have vitamin D3
      deficiency compared with normal GFR. 25-(OH) D3 levels were associated with a
      greater incidence of all-cause hospitalization, hypoalbuminemia, and vitamin B12
      deficiency. However, there was no relationship between inflammatory markers and
      vitamin D3 levels. In 25-(OH) D3 deficient patients, inflammatory markers can be
      related to other inflammatory and infectious status such as malnutrition and
      cachexia. We believed that there must be a relationship between vitamin
      deficiency and inflammatory markers due to other causes than low 25-(OH) D3
      status. 

PMID- 23878539
TI  - Determinants of microbial load in infected diabetic foot ulcers: a pilot study.
AB  - We examined the determinants of microbial load in infected diabetic foot ulcers
      in 62 patients (38 men and 24 women, mean age: 65.63 +/- 12.71 years) with
      clinically infected diabetic foot ulcers. Tissue cultures were taken from ulcers
      by 4 mm punches. Ulcer grade (University of Texas classification), neuropathy
      disability score (NDS), neuropathy symptom score (NSS), ankle-brachial index
      (ABI), perfusion, extent, depth, infection, and sensation (PEDIS) grade of
      diabetic foot infection, and laboratory parameters were evaluated in all
      patients. Total microbial load was positively correlated with the number of
      isolates on tissue cultures (r s = 0.544, P < 0.001), white blood cell count
      (WBC) (r s = 0.273, P = 0.032), and platelet count (PLT) (r s = 0.306, P =
      0.015). It also exhibited a borderline insignificant positive correlation with
      PEDIS infection grade (r s = 0.246, P = 0.053). In stepwise linear regression
      analysis, the number of isolates on tissue cultures and WBC were identified as
      the only two significant parameters accounting for 38% of the variation in the
      log of total microbial load (adjusted R (2) = 0.380, P < 0.001). In conclusion,
      patients with infected diabetic foot ulcer exhibit a positive correlation of
      total microbial load with the number of isolates on tissue cultures, WBC and PLT.

PMID- 23878540
TI  - Antibacterial Effect of Juglans Regia Bark against Oral Pathologic Bacteria.
AB  - Background. In this study antimicrobial effect of ethanolic and aqueous extracts
      of Juglans regia bark in Iran was evaluated on four different oral bacteria,
      Streptococcus mutans, Streptococcus salivarius, Streptococcus sanguis, and
      Staphylococcus aureus. Methods. Aqueous and ethanol extracts of Juglans regia
      bark were prepared by using disk diffusion technique and Minimal Inhibitory
      Concentration (MIC) methods. Tetracycline 30  MU g and Erythromycin 15  MU g were
      used as positive control and water as negative control in disk diffusion and MIC
      methods. Data were analyzed by ANOVA test. Results. The results showed that S.
      sanguis and S. mutans were the most sensitive and the most resistant bacteria
      against ethanolic and aqueous extracts, respectively. Ethanolic extract had
      significant antibacterial effect against all tested bacteria. Aqueous extract did
      not show antibacterial effect on S. mutans, in contrast to ethanolic extract.
      Aqueous extract had significantly antibacterial effect against Staphylococcus
      aureus, S. salivarius, and S. sanguis compared to control (P < 0.0001), but it
      did not show effect on S. mutans when compared with Erythromycin. According to
      the obtained MIC values, ethanol extract of Juglans regia bark had the lowest
      rate. Conclusion. The results may provide the basis for using natural
      antimicrobial substance for oral hygiene prophylaxis purposes. 

PMID- 23878542
TI  - Abiotic and Biotic Factors Affecting Resting Spore Formation in the Mite Pathogen
      Neozygites floridana.
AB  - Neozygites floridana is an obligate mite pathogenic fungus in the
      Entomophthoromycota. It has been suggested that resting spores of this fungus are
      produced as a strategy to survive adverse conditions. In the present study,
      possible mechanisms involved in the regulation of resting spore formation were
      investigated in the hosts Tetranychus urticae and Tetranychus evansi. Abiotic and
      biotic factors mimicking conditions that we, based on earlier field studies,
      thought might induce resting spores in temperate and tropical regions were tested
      with isolates from Norway and Brazil. A total of 42 combinations of conditions
      were tested, but only one induced the formation of a high number of resting
      spores in only one isolate. The Brazilian isolate ESALQ1420 produced a large
      number of resting spores (51.5%) in T. urticae at a temperature of 11 degrees C,
      photoperiod of 10L:14D, and light intensity of 42-46 ( MU mol m(-2) s(-1)) on
      nonsenescent plants (nondiapausing females). Resting spores of the Brazilian N.
      floridana isolate ESALQ1421 were found at very low levels (up to 1.0%). Small
      percentages of T. urticae with resting spores (0-5.0%) were found for the
      Norwegian isolate NCRI271/04 under the conditions tested. The percentages of
      resting spores found for the Norwegian isolate in our laboratory studies are
      similar to the prevalence reported in earlier field studies. 

PMID- 23878543
TI  - Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease.
AB  - Immunoglobulin free light chains are produced in excess during normal antibody
      synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy.
      In polyclonal hypergammaglobulinemia related to the Sjogren syndrome or systemic
      lupus, erythematosus serum free light chain levels are increased and could
      correlate with disease activity. We show here that the kappa (P < 0.0001) and
      lambda (P = 0.0003) free light chains and the kappa  :  lambda ratio (P = 0.0049)
      are increased in sixteen patients with IgG4-related disease when compared to
      healthy controls. The increase of kappa and lambda free light chains probably
      reflects the marked polyclonal B cell activation of the disease. We could not
      assess in this small cohort of patients a significative correlation of serum free
      light chain levels and disease activity or extension. 

PMID- 23878541
TI  - Application of calcium phosphate materials in dentistry.
AB  - Calcium phosphate materials are similar to bone in composition and in having
      bioactive and osteoconductive properties. Calcium phosphate materials in
      different forms, as cements, composites, and coatings, are used in many medical
      and dental applications. This paper reviews the applications of these materials
      in dentistry. It presents a brief history, dental applications, and methods for
      improving their mechanical properties. Notable research is highlighted regarding
      (1) application of calcium phosphate into various fields in dentistry; (2)
      improving mechanical properties of calcium phosphate; (3) biomimetic process and
      functionally graded materials. This paper deals with most common types of the
      calcium phosphate materials such as hydroxyapatite and tricalcium phosphate which
      are currently used in dental and medical fields. 

PMID- 23878544
TI  - The obstetric consequences of female genital mutilation/cutting: a systematic
      review and meta-analysis.
AB  - Various forms of female genital mutilation/cutting (FGM/C) have been performed
      for millennia and continue to be prevalent in parts of Africa. Although the
      health consequences following FGM/C have been broadly investigated, divergent
      study results have called into question whether FGM/C is associated with
      obstetric consequences. To clarify the present state of empirical research, we
      conducted a systematic review of the scientific literature and quantitative meta
      analyses of the obstetric consequences of FGM/C. We included 44 primary studies,
      of which 28 were comparative, involving almost 3 million participants. The
      methodological study quality was generally low, but several studies reported the
      same outcome and were sufficiently similar to warrant pooling of effect sizes in
      meta-analyses. The meta-analyses results showed that prolonged labor, obstetric
      lacerations, instrumental delivery, obstetric hemorrhage, and difficult delivery
      are markedly associated with FGM/C, indicating that FGM/C is a factor in their
      occurrence and significantly increases the risk of delivery complications. There
      was no significant difference in risk with respect to cesarean section and
      episiotomy. These results can make up the background documentation for health
      promotion and health care decisions that inform work to reduce the prevalence of
      FGM/C and improve the quality of services related to the consequences of FGM/C. 

PMID- 23878545
TI  - Management of early stage, high-risk endometrial carcinoma: preoperative and
      surgical considerations.
AB  - Endometrial cancer is the most common gynecologic malignancy in the developed
      world. Most cases are diagnosed at an early stage and have low-grade histology,
      portending an overall excellent prognosis. There exists a subgroup of patients
      with early, high-risk disease, whose management remains controversial, as current
      data is clouded by inclusion of early stage tumors with different high-risk
      features for recurrence, unstandardized protocols for surgical staging, and an
      evolving staging system by which we are grouping these patients. Here, we present
      preoperative and intraoperative considerations that should be taken into account
      when planning surgical management for this population of patients. 

PMID- 23878546
TI  - Plantar erythrodysesthesia caused by antiretroviral treatment: a case report and
      review of the literature.
AB  - Palmoplantar erythrodysesthesia is an uncommon localised cutaneous reaction to
      certain chemotherapeutic agents and characterized by painful palmoplantar
      erythema and dysesthesia. To the best of our knowledge, we report the first case
      of plantar erythrodysesthesia in a 40-year-old male patient receiving an
      antiretroviral combination therapy for HIV. 

PMID- 23878547
TI  - Amyloid Beta peptides differentially affect hippocampal theta rhythms in vitro.
AB  - Soluble amyloid beta peptide (A beta ) is responsible for the early cognitive
      dysfunction observed in Alzheimer's disease. Both cholinergically and
      glutamatergically induced hippocampal theta rhythms are related to learning and
      memory, spatial navigation, and spatial memory. However, these two types of theta
      rhythms are not identical; they are associated with different behaviors and can
      be differentially modulated by diverse experimental conditions. Therefore, in
      this study, we aimed to investigate whether or not application of soluble A beta
      alters the two types of theta frequency oscillatory network activity generated in
      rat hippocampal slices by application of the cholinergic and glutamatergic
      agonists carbachol or DHPG, respectively. Due to previous evidence that
      oscillatory activity can be differentially affected by different A beta peptides,
      we also compared Abeta 25-35 and Abeta 1-42 for their effects on theta rhythms in
      vitro at similar concentrations (0.5 to 1.0  MU M). We found that Abeta 25-35
      reduces, with less potency than Abeta 1-42, carbachol-induced population theta
      oscillatory activity. In contrast, DHPG-induced oscillatory activity was not
      affected by a high concentration of Abeta 25-35 but was reduced by Abeta 1-42.
      Our results support the idea that different amyloid peptides might alter specific
      cellular mechanisms related to the generation of specific neuronal network
      activities, instead of exerting a generalized inhibitory effect on neuronal
      network function. 

PMID- 23878548
TI  - The asthma phenotype in the obese: distinct or otherwise?
AB  - Asthma is a heterogenous disorder that can be classified into several different
      phenotypes. Recent cluster analyses have identified an "obese-asthma" phenotype
      which is characterized by late onset, female predominance and lack of atopy. In
      addition, obesity among early-onset asthmatics clearly exists and heightens the
      clinical presentation. Observational studies have demonstrated that asthma among
      the obese has a clinical presentation that is more severe, harder to control, and
      is not as responsive to standard controller therapies. While weight loss studies
      have demonstrated improvement in asthma outcomes, further studies need to be
      performed. The current knowledge of the existence of two obesity-asthma
      phenotypes (early- versus late-onset asthma) should encourage investigators to
      study these entities separately since just as they have distinct presentations,
      their course, response to therapies, and weight loss strategies may be different
      as well. 

PMID- 23878549
TI  - Prospective multi-center dosimetry study of low-dose Iodine-125 prostate
      brachytherapy performed after transurethral resection.
AB  - PURPOSE: To evaluate in a multicenter setting the ability of centers to perform
      pre-implant permanent prostate brachytherapy planning, fulfilling dosimetric
      goals and constraints based on the Groupe de Curietherapie-European Society for
      Radiotherapy and Oncology guidelines in the setting of implantation after prior
      prostate transurethral resection (TURP). MATERIAL AND METHODS: A reference
      transrectal ultrasound image set of the prostate gland from a patient who had
      undergone TURP was used. Contouring of the prostate, clinical target volume and
      organs at risk was performed by the coordinating center. Goals and constraints
      regarding the dosimetry were defined. RESULTS: Seventeen of twenty-five centers
      invited to participate were able to import the Digital Imaging and Communications
      in Medicine-images into their planning computer and plan the implant using the
      defined guidelines. All centers were able to plan treatment, and achieve the
      recommended objectives and constraints. However, sector analysis has shown a risk
      of under-dosage in the anterior part of the prostate. CONCLUSIONS: Correct pre
      implantation planning with adherence to protocol guidelines and in compliance
      with defined dosimetric constraints seems feasible in a post-TURP setting, at
      least on a theoretical basis. A prospective study evaluating the outcome of
      prostate brachytherapy performed after TURP can therefore be undertaken with an
      expectation of a correct dosimetry in the multicenter setting.

PMID- 23878550
TI  - High-dose-rate interstitial brachytherapy for liver metastases: first study from
      India.
AB  - PURPOSE: To study the safety and efficacy of high-dose-rate interstitial
      brachytherapy (HDRIBT) in patients with liver metastases (LM). MATERIAL AND
      METHODS: Between 2009 and 2011, 10 patients with 12 metastatic lesions in the
      liver were enrolled in this prospective trial. All patients had either refused
      surgery or found ineligible for surgery due to various factors. Under CT
      guidance, 16 gauze blind end stainless steel or rigid plastic brachytherapy
      needle was inserted in the center of lesion through the percutaneous route.
      Generally, a single interstitial brachytherapy (IBT) needle for lesions up to 3
      cm and multiple needles for lesions more than 3 cm in diameter were inserted.
      Treatment was delivered with a single high-dose-rate (HDR) dose of 20 Gy
      prescribed to the target. The needles were removed immediately after the
      treatment. The endpoints of study were acute complications and local control of
      the disease. RESULTS: The median size of the lesion was 3.8 cm (2.7-7.0 cm). The
      average time for the entire IBT procedure was 65 minutes (50-105 minutes). Median
      follow up was 9 months (3-17 months). None of the patients had fatal
      complications. Minor complications like pain, nausea/vomiting, and asymptomatic
      pleural effusion were observed in 3, 2 and 1 patients, respectively. Local
      control rate at 12 months was 75%. The 1-year local progression free survival
      (LPFS) was 33%. CONCLUSION: Although limited by small sample size, the results of
      our first study from India suggest that HDRIBT is a safe and effective non
      surgical option for LM.

PMID- 23878551
TI  - Adjuvant and definitive radiation therapy for primary carcinoma of the vagina
      using brachytherapy and external beam radiation therapy.
AB  - PURPOSE: To report the outcomes of patients receiving vaginal brachytherapy
      and/or external beam radiation therapy (EBRT) for primary vaginal cancer.
      MATERIAL AND METHODS: Between 1983 and 2009, 63 patients received brachytherapy
      and/or EBRT for primary tumors of the vagina at a single tertiary center. Patient
      data was collected via chart review. The Kaplan-Meier method was used to
      calculate actuarial pelvic local control (LC), disease-free survival (DFS),
      overall survival (OS), and severe late toxicity rates. Acute and late toxicities
      were scored according to the Common Terminology Criteria for Adverse Events
      version 3 (CTCAE v3.0). RESULTS: Median follow up was 44.2 months. Patients with
      early stage disease (stages I and II) had significantly improved 5-year OS when
      compared to patients with locally advanced disease (stages III and IVA) (73.3 vs.
      34.4%, p = 0.032). Patients with greater than 1/3 vaginal involvement had
      significantly worse prognosis than patients with tumors involving 1/3 or less of
      the vagina, with the later having superior DFS (84.0 vs. 52.4%, p = 0.007) and LC
      (86.9 vs. 60.4%, p = 0.018) at 5-years. Age, histology, and brachytherapy
      technique did not impact treatment outcomes. The 5-year actuarial grade 3 or
      higher toxicity rate was 23.1% (95% CI: 10.6-35.6%). Concurrent chemotherapy had
      no impact on outcomes or toxicity in this analysis. CONCLUSIONS: Success of
      treatment for vaginal cancer depends primarily on disease stage, but other
      contributing factors such as extent of vaginal involvement and tumor location
      significantly impact outcomes. Treatment of vaginal cancer with primary
      radiotherapy yields acceptable results with reasonable toxicity rates. Management
      of this rare malignancy requires a multidisciplinary approach to appropriately
      optimize therapy.

PMID- 23878552
TI  - Malignant obstructive jaundice - brachytherapy as a tool for palliation.
AB  - PURPOSE: Malignant obstructive jaundice (MOJ) is relieved by stenting via
      endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous
      transhepatic cholangiography and biliary drainage (PTCD). Stent occlusion rates
      of 30-45% have been reported in literature due to tumor ingrowth or overgrowth.
      We prospectively evaluated the feasibility and the role of intraluminal
      brachytherapy (ILBT) in preventing stent blockage in patients with MOJ after PTCD
      and stenting. MATERIAL AND METHODS: Twelve patients with MOJ who underwent PTCD
      followed by self expanding metallic stent (SEMS) placement were prospectively
      enrolled in this study. Written informed consent was obtained. Intraluminal
      brachytherapy was done once patient was stable and serum bilirubin was less than
      2 mg% or 50% of baseline value. On the day of ILBT, 6 French brachytherapy
      catheters were placed across malignant stricture under fluoroscopic guidance with
      placement of the tip 1 cm distal to stricture. A dose of 10 to 14 Gy was
      delivered at 1 cm from central axis of the source. Suitable patients also
      received external beam radiotherapy (EBRT) with weekly concurrent chemotherapy.
      RESULTS: All patients tolerated the procedure well with minimal acute and late
      toxicities. Duodenal ulceration was observed in 1 patient. At a mean follow up of
      10.25 months (5-24 months), stents were patent in 10/12 subjects and stent
      patency duration of 9.8 months (5-22) was reported. CONCLUSIONS: Intraluminal
      brachytherapy post PTCD is feasible and effective in preventing stent occlusion
      with minimal acute and late toxicities.

PMID- 23878553
TI  - The phylogeny of permanent prostate brachytherapy.
AB  - Permanent prostate brachytherapy has been practiced for more than a century. This
      review examines the influence of earlier procedures on the modern transperineal
      ultrasound-directed technique. A literature review was conducted to examine the
      origin of current clinical practice. The dimensions of the modern brachytherapy
      seed, the prescription dose, and implant/teletherapy sequencing are vestigial
      features, which may be suboptimal in the current era of low-energy photon
      emitting radionuclides and computerized dose calculations. Although the modern
      transperineal permanent prostate implant procedure has proven to be safe and
      effective, it should undergo continuous re-evaluation and evolution to ensure
      that its potential is maximized. 

PMID- 23878554
TI  - Feasibility study and optimum loading pattern of a multi-ring inflatable
      intravaginal applicator.
AB  - PURPOSE: A cylinder applicator is the standard treatment device for intravaginal
      brachytherapy. However, they are limited in their ability to simultaneously spare
      the organs at risk (OAR), and reduce the hot spot in the vaginal mucosa, while
      achieving adequate dose conformality. This study aims to compare the dosimetric
      characteristics of single and multi-channel cylinders, and utilizes volume point
      dose optimizations to investigate the feasibility and optimum loading method for
      a multi-ring inflatable intravaginal applicator. MATERIAL AND METHODS: STUDIES
      WERE DESIGNED TO: (1) test the feasibility of multi-ring applicators, (2) compare
      dose distributions between different multi-channel applicators and loading
      patterns, (3) test non-uniform prescription depths around the multi-ring
      cylinder. RESULTS: Compared to a cylinder with a single central channel, a
      cylinder with 6 lumina arranged around the periphery, providing the lumina had
      adequate distance to the cylinder surface, could reduce dose beyond the
      prescription depth. However, when the number of outer lumina increased from 6 to
      12, no further dose reduction could be achieved and the high dose volume close to
      the surface of the cylinder increased. Moreover, an additional ring, with lumina
      further away from the surface, provided increased dose shaping capabilities,
      allowing for individualized dose distributions. CONCLUSIONS: Dose could be
      reduced to normal tissue and the inner mucosa, and better conformity was seen to
      unique anatomical shapes. A modified peripheral loading pattern provided the
      optimum dose distribution, yielding good conformity, dose sparing at adjacent
      organs, and dose reduction in the high dose region of the vaginal mucosa.

PMID- 23878555
TI  - High resolution (3 Tesla) MRI-guided conformal brachytherapy for cervical cancer:
      consequences of different high-risk CTV sizes.
AB  - PURPOSE: To evaluate conventional brachytherapy (BT) plans using dose-volume
      parameters and high resolution (3 Tesla) MRI datasets, and to quantify dosimetric
      benefits and limitations when MRI-guided, conformal BT (MRIG-CBT) plans are
      generated. MATERIAL AND METHODS: Fifty-five clinical high-dose-rate BT plans from
      14 cervical cancer patients were retrospectively studied. All conventional plans
      were created using MRI with titanium tandem-and-ovoid applicator (T&O) for
      delivery. For each conventional plan, a MRIG-CBT plan was retrospectively
      generated using hybrid inverse optimization. Three categories of high risk (HR)
      CTV were considered based on volume: non-bulky (< 20 cc), low-bulky (> 20 cc and
      < 40 cc) and bulky (>= 40 cc). Dose-volume metrics of D90 of HR-CTV and D2cc and
      D0.1cc of rectum, bladder, and sigmoid colon were analyzed. RESULTS: Tumor
      coverage (HR-CTV D90) of the conventional plans was considerably affected by the
      HR-CTV size. Sixteen percent of the plans covered HR-CTV D90 with the
      prescription dose within 5%. At least one OAR had D2cc values over the GEC-ESTRO
      recommended limits in 52.7% of the conventional plans. MRIG-CBT plans showed
      improved target coverage for HR-CTV D90 of 98 and 97% of the prescribed dose for
      non-bulky and low-bulky tumors, respectively. No MRIG-CBT plans surpassed the
      D2cc limits of any OAR. Only small improvements (D90 of 80%) were found for large
      targets (> 40 cc) when using T&O applicator approach. CONCLUSIONS: MRIG-CBT plans
      displayed considerable improvement for tumor coverage and OAR sparing over
      conventional treatment. When the HR-CTV volume exceeded 40 cc, its improvements
      were diminished when using a conventional intracavitary applicator.

PMID- 23878556
TI  - Tooth auto-transplantation as an alternative treatment option: A literature
      review.
AB  - Rapidly evolving implantation and alveolar ridge reconstruction techniques
      created a new area in modern dentistry where tooth loss is no longer a problem.
      Endless variations of implant's length, diameter, surface, and design along with
      autogenous, alogenous, aloplastic, or xenogenous bone substitutes made it
      possible to recreate physiological occlusion, esthetic and masticatory function.
      However, none of nowadays technologies in implant dentistry have the potential to
      adapt to a growth and development changes of a child's jaw. Therefore, patient's
      young age is a restriction for implantation and a particular challenge for a
      dentist willing to restore missing tooth. Thus, tooth auto-transplantation can be
      a good choice for treatment. The objective of this review is to underline the
      biologic principles required for successful auto-transplantation of teeth.
      Limits, indications, technique, and prognosis will be analyzed. 

PMID- 23878557
TI  - Peri-implant esthetics assessment and management.
AB  - Providing an esthetic restoration in the anterior region of the mouth has been
      the basis of peri-implant esthetics. To achieve optimal esthetics, in implant
      supported restorations, various patient and tooth related factors have to be
      taken into consideration. Peri-implant plastic surgery has been adopted to
      improve the soft tissue and hard tissue profiles, during and after implant
      placement. The various factors and the procedures related to enhancement of peri
      implant esthetics have been discussed in this review article. 

PMID- 23878558
TI  - A comparative study of accuracy of linear measurements using cone beam and multi
      slice computed tomographies for evaluation of mandibular canal location in dry
      mandibles.
AB  - BACKGROUND: Cross- sectional tomograms have been used for optimal pre-operative
      planning of dental implant placement. The aim of the present study was to assess
      the accuracy of Cone Beam Computed Tomography (CBCT) measurements of specific
      distances around the mandibular canal by comparing them to those obtained from
      Multi-Slice Computed Tomography (MSCT) images. MATERIALS AND METHODS: Ten hemi
      mandible specimens were examined using CBCT and MSCT. Before imaging, wires were
      placed at 7 locations between the anterior margin of the third molar and the
      anterior margin of the second premolar as reference points. Following distances
      were measured by two observers on each cross-sectional CBCT and MSCT image:
      Mandibular Width (W), Length (L), Upper Distance (UD), Lower Distance (LD),
      Buccal Distance (BD), and Lingual Distance (LID). The obtained data were
      evaluated using SPSS software, applying paired t-test and intra-class correlation
      coefficient (ICC). RESULTS: There was a significant difference between the values
      obtained by MSCT and CBCT measurement for all areas such as H, W, UD, LD, BD, and
      LID, (P < 0.001), with a difference less than 1 mm. The ICC for all distances by
      both techniques, measured by a single observer with a one week interval and
      between 2 observers was 99% and 98%, respectively. Comparing the obtained data of
      both techniques indicates that the difference between two techniques is 2.17%
      relative to MSCT. CONCLUSION: The results of this study showed that there is
      significant difference between measurements obtained by CBCT and MSCT. However,
      the difference is not clinically significant.

PMID- 23878559
TI  - Health literacy among Indian adults seeking dental care.
AB  - BACKGROUND: Poor literacy can impede one's ability not only to seek out needed
      health information but also to process, understand and use it to make appropriate
      health care decisions. The objective of the study was to assess the health
      literacy among adult patients seeking oral health care at in a private dental
      hospital in Bangalore, Karnataka, India. MATERIALS AND METHODS: A cross sectional
      questionnaire survey was carried out on 500 subjects. The questionnaire designed
      by Chew and colleagues (2004) was modified and used as the survey instrument. To
      be eligible to participate in the study, the participants had to be aged above 18
      years and able to read or write English/Kannada (local language). Analysis of
      variance (ANOVA) and Student's t-test (two tailed, independent) was used to find
      the significance of study parameters at 95% confidence interval. RESULTS: About
      60.4% of the subjects had low health literacy level, 29.4% average and only 10.2%
      had high health literacy levels. Age and educational qualification had a
      suggestive significant difference with the mean health literacy scores while
      gender did not have any significant difference. Subjects who had completed post
      graduation (57.8%) too had low health literacy levels. CONCLUSION: A large number
      of patients have low levels of health literacy that may interfere with their
      ability to process and understand basic health information.

PMID- 23878560
TI  - Infection control practices in dental school: A patient perspective from Saudi
      Arabia.
AB  - BACKGROUND: Routine use of gloves, masks and spectacles are important in
      infection control. Aim of this study was to assess the knowledge and attitudes of
      infection control measures among the patients attending clinics of Riyadh
      Colleges of Dentistry and Pharmacy (RCsDP) in Saudi Arabia. MATERIAL AND METHODS:
      It was a cross-sectional descriptive study of a convenient sample of dental
      patients attending dental clinics of RCsDP. A structured, close ended, self
      administered questionnaire was distributed to 350 patients and a response rate of
      86% was obtained. Questionnaireconsisted of series of queries related to
      knowledge and attitudes of patients towards infection control measures. Data
      analysis included frequency distribution tables, Mann-Whitney and Kruskal-Wallis
      tests. Level of significance was set at P < 0.05. RESULTS: Final study sample
      included 301 patients (147 males and 154 females). Almost 99%, 93.7% and 82.7% of
      the patients agreed that dentist should wear gloves, face mask and spectacles
      while providing treatment. However, 60.1%, 30% of the patients said that HIV and
      hepatitis-B infections can spread in dental clinics. Half of the patients felt
      that they were likely to contract AIDS and 77.7% refused to attend clinics if
      they knew that AIDS and Hepatitis-B patients treated there. Only 25.2% said that
      autoclave is the best method of sterilization. A significantly higher knowledge
      of infection control was observed among the previous dental visitors compared to
      the first time visitors to the dental clinics (P < 0.05). CONCLUSIONS: Patients
      revealed adequate knowledge towards the use of gloves, face mask and spectacles
      by dentist. However, their knowledge regarding the spread of Hepatitis-B, HIV
      infection and use of autoclave was poor. Previous visitor of dental clinics
      showed higher knowledge of infection control as compared to the first time
      visitors. Many patients expressed their negative attitudes towards dental care
      due to AIDS and Hepatitis-B concerns.

PMID- 23878561
TI  - Analysis of the immunoexpression of Ki-67 and Bcl-2 in the pericoronal tissues of
      impacted teeth, dentigerous cysts and gingiva using software image analysis.
AB  - BACKGROUND: Pericoronal tissue is the soft tissue located between the bony crypt
      and the impacted tooth, which is histologically composed of fibrous connective
      tissue and is usually lined by the reduced enamel epithelium. Increased
      epithelial cell proliferation in the pericoronal tissue is associated with
      pathological changes such as development of an odontogenic cyst or an epithelial
      odontogenic tumor. This study is an attempt to evaluate and compare the
      proliferative index in the epithelium surrounding the impacted third molar teeth,
      dentigerous cysts, and gingiva. MATERIALS AND METHODS: A case control study on
      pericoronal tissues and dentigerous cysts was carried out using immunomarkers.
      Forty pericoronal tissues were obtained from asymptomatic impacted third molars
      with pericoronal radiolucency less than 2.5 mm. Samples of 20 dentigerous cysts
      and normal gingiva were also included. Routine hematoxylin and eosin and
      immunostaining for Ki-67, a cell proliferation marker and Bcl-2, an anti
      apoptotic protein were performed on sections of pericoronal tissues, dentigerous
      cysts, and gingival tissues. The percentage of Ki-67-positive cells and Bcl-2
      positive areas was found using the DigiProTM version 4.0 Image analysis software.
      Bcl-2 immunopositivity and Ki-67-Li were analyzed using the Chi-square test and
      paired t-test. P- values of less than .05 were considered to indicate statistical
      significance. RESULTS: The immunohistochemical analysis revealed overexpression
      of Bcl-2 in the pericoronal tissues with squamous metaplasia, which was
      comparable to the dentigerous cyst. Ki-67 Li of the pericoronal tissue with
      squamous metaplasia was equal to the proliferative index of the dentigerous cyst.
      The expression of Ki-67 Li and inflammatory cells were highly significant (P <
      0.0001). CONCLUSIONS: The results of this study indicate that the pericoronal
      tissues of asymptomatic impacted third molars may be actively proliferating and
      normal pericoronal radiolucency cannot serve as an indicator for the
      differentiation potential.

PMID- 23878562
TI  - Connective tissue graft vs. emdogain: A new approach to compare the outcomes.
AB  - BACKGROUND: The aim of this clinical trial study was to clinically evaluate the
      use of enamel matrix protein derivative combined with the coronally positioned
      flap to treat gingival recession compared to the subepithelial connective tissue
      graft by a new method to obtain denuded root surface area. MATERIALS AND METHODS:
      Thirteen patients, each with two or more similar bilateral Miller class I or II
      gingival recession (40 recessions) were randomly assigned to the test (enamel
      matrix protein derivative + coronally positioned flap) or control group
      (subepithelial connective tissue graft). Recession depth, width, probing depth,
      keratinized gingival, and plaque index were recorded at baseline and at one,
      three, and six months after treatment. A stent was used to measure the denuded
      root surface area at each examination session. Results were analyzed using
      Kolmogorov-Smirnov, Wilcoxon, Friedman, paired-sample t test. RESULTS: The
      average percentages of root coverage for control and test groups were 63.3% and
      55%, respectively. Both groups showed significant keratinized gingival increase
      (P < 0.05). Recession depth decreased significantly in both groups. Root surface
      area was improved significantly from baseline with no significant difference
      between the two study groups (P > 0.05). The results of Friedman test were
      significant for clinical indices (P < 0.05), except for probing depth in control
      group (P = 0.166). CONCLUSION: Enamel matrix protein derivative showed the same
      results as subepithelial connective tissue graft with relatively easy procedure
      to perform and low patient morbidity.

PMID- 23878563
TI  - Root-end filling with cement-based materials: An in vitro analysis of bacterial
      and dye microleakage.
AB  - BACKGROUND: One ideal property of a root-end filling material is its apical
      sealing ability. The aim of this in vitro study was to assess bacterial and dye
      microleakage of white and gray mineral trioxide aggregate (WMTA and GMTA),
      Portland cement and calcium-enriched mixture (CEM) cement used as root-end
      filling material, and to assess the agreement between these two test methods.
      MATERIALS AND METHODS: Fifty-four single-rooted teeth were used. The roots were
      randomly divided into four study and two control groups. After decoronation, root
      canals were instrumented and filled with gutta-percha and AH26 sealer. Root-ends
      were resected 3 mm above the root-end and 3 mm deep cavities were prepared. Root
      end cavities were filled with each material. Enterococcus faecalis and methylene
      blue dye were used for determination of bacterial and dye leakage respectively.
      Data were analyzed using Fisher's Exact Test, one-way ANOVA, Kaplan-Meier
      analysis, and Cohen's Kappa. RESULTS: There was 100% bacterial leakage in
      Portland cement and CEM cement, 58.3% in GMTA, and 91.7% in WMTA. GMTA showed
      significantly less bacterial leakage than Portland cement and CEM cement (P <
      0.05). In those samples with leakage occurrence, times of observation of leakage
      were not significantly different; however, by survival analysis, the results of
      the GMTA group were significantly different from those of the CEM cement and
      Portland groups. The difference in complete dye leakage was not significant.
      There was poor agreement between dye and bacterial leakage methods. CONCLUSION:
      CEM cement provides leakage results comparable to other commonly used root-end
      filling materials such as WMTA.

PMID- 23878565
TI  - Fracture resistance of overtly flaring root canals filled with resin-based
      obturation material.
AB  - BACKGROUND: Reinforcement of root canals obturated with Resilon was reported by
      several investigators, but no studies reported the reinforcement of overtly
      flared root canals obturated with Resilon material. The aim of this study was to
      investigate the fracture resistance of overtly flared root canals filled with
      Resilon as compared to similar root canals filled with gutta-percha (GP).
      MATERIALS AND METHODS: Sixty single-rooted premolars were divided randomly into
      six groups. Group 1 served as control group. The control group was sub-divided
      into two groups, a negative group and a positive group. The negative group
      consisted of root canals that were only cleaned from residual pulpal tissues,
      however, the positive group had prepared and overtly flared root canals without
      obturation. Groups 2 and 4 were shaped using 0.04 taper rotary files, while
      groups 3 and 5 were shaped using 0.06 taper rotary files. Before obturation, the
      last four groups were further flared coronally with a reverse cone diamond bur.
      Groups 2 and 3 were obturated with GP and a resin-based sealer, while groups 4
      and 5 were obturated with Resilon and Epiphany self-etching primer and Epiphany
      sealer. Roots were then fixed into a universal testing machine and vertically
      loaded until fracture. SPSS software (Release 9.0 for Windows, SPSS, Chicago,
      USA) was used to perform the statistical analysis. RESULTS: Fracture resistance
      measurements showed that there were differences in resistance to fracture among
      the experimental groups (ANOVA, P < 0.0001). Mean values of the loading force
      applied to the negative control group were the highest at 1.81 KN, whereas the
      mean values for the Resilon groups (Groups 4 and 5) at 1.13 KN and 1.54 KN were
      found to be higher than the GP groups (Groups 2 and 3) at 0.45 KN and 0.88 KN,
      respectively. Tukey's post hoc test showed that there was no statistical
      difference between the mean values of the negative control group and Group 5 (P =
      0.69). CONCLUSION: Obturation of overtly flared roots with Resilon material
      increased the resistance of these teeth to vertical root fracture.

PMID- 23878566
TI  - Evaluation of properties of irreversible hydrocolloid impression materials mixed
      with disinfectant liquids.
AB  - BACKGROUND: Addition of disinfectant to irreversible hydrocolloid impression
      materials can eliminate the disinfection step to avoid dimensional changes
      associated with it. The aim of the present study was to evaluate the effect of
      various disinfectant mixing liquids on the properties of commercially available
      irreversible hydrocolloid impression materials. MATERIALS AND METHODS: Four
      commercially available irreversible hydrocolloid impression materials (Zelgan,
      Vignette, Tropicalgin, and Algitex) were mixed with disinfectant liquid
      containing chlorhexidine (0.1 and 0.2%) and sodium hypochlorite (0.1 and 0.5%).
      After mixing with disinfectant liquids, materials were evaluated for pH changes
      during gelation, gelation time, flow, gel strength, permanent deformation and
      detail reproduction. RESULTS: Significant changes in gelation time were observed
      in irreversible hydrocolloid impression materials upon mixing with disinfectant
      liquids. In general, chlorhexidine increased the gelation time, whereas sodium
      hypochlorite reduced it. However, no significant changes in the flow were
      observed both with chlorhexidine and sodium hypochlorite. Gel strength was found
      to decrease when mixed with chlorhexidine, whereas an increase in gel strength
      was observed upon mixing with sodium hypochlorite. Permanent deformation of the
      most irreversible hydrocolloid impression materials was below the specification
      limit even after mixing with disinfectant liquids. Sodium hypochlorite
      significantly reduced the surface detail reproduction, whereas no change in
      detail reproduction was observed with chlorhexidine. CONCLUSION: Chlorhexidine
      solution can be used to mix irreversible hydrocolloid impression materials in
      regular dental practice as it did not significantly alter the properties. This
      may ensure effective disinfection of impressions.

PMID- 23878564
TI  - Proliferative and inductive effects of Cyclosporine a on gingival fibroblast of
      child and adult.
AB  - BACKGROUND: Gingival overgrowth is a serious side-effect that accompanies the use
      of Cyclosporin A (CsA). Up to 97% of the transplant recipient children, who were
      submitted to CsA therapy, have been reported to suffer from this side-effect.
      Several conflicting theories have been proposed to explain the fibroblast's
      function in CsA-induced gingival overgrowth. The aim of this study is to assess
      the proliferation of gingival fibroblasts and levels of released cytokines after
      being exposed to CsA, in both adults and pediatric groups, and to make a
      comparison between the results of the two groups. MATERIALS AND METHODS: The
      adult fibroblast samples were derived from four healthy adults, aged 35 to 42
      years and pediatric samples were obtained from four healthy children, age between
      four and eleven years. Tissue samples were plated in Dulbecco's Modified Eagle
      Medium (DMEM) containing 10% fetal bovine serum (FBS), Streptomycin and
      Penicillin. The samples were cultured in 25 cm(2) plates containing 5% CO2, and
      incubated at 37 degrees C. The cells used for all the experiments were at the
      fourth passage. The concentration of PGE2, IL-1beta, IL-6, IL-8, TNF-alpha, and
      TGF-beta1 was determined by the enzyme-linked immunosorbent assay (ELISA) and the
      proliferation rate was assessed by the MTT assay. Alpha error levels were set as
      0.05. RESULTS: CsA stimulated significantly higher levels of IL-6, IL-8 and TGF
      beta1 in adult gingival fibroblasts than it did in the control group; whereas,
      the expression of IL-1beta and PGE2 in the fibroblasts exposed to CsA was
      significantly weaker (P < 0.05). The fibroblasts in the two groups did not reveal
      any noticeable difference in the production of TNF-alpha. Furthermore, cell
      proliferation in the CsA group was not significantly higher than that in the
      control group. No significant differences in cytokines TNF-alpha and IL-1beta
      were noted between the two groups. The results indicated that CsA stimulated cell
      proliferation in the pediatric fibroblast cell line. Comparison between the
      results in the adult and pediatric groups demonstrated that the levels of IL
      1beta, IL-6, IL-8, and PGE2 were significantly higher in the pediatric group than
      in the adult group; however, statistics showed no significant difference in the
      levels of TNF-alpha and TGF-beta1 and CsA-induced proliferation between these two
      groups. CONCLUSIONS: The mechanism of a CsA-induced fibroblast overgrowth may
      converge on the steps involving fibroblast proliferation and cytokine network
      including IL-6, IL-8, IL-1beta, TGF-beta1, and PGE2, in both adults and
      pediatrics. As the prevalence and intensity of drug-induced gingival overgrowth
      is more serious in the pediatrics. As group than in adults, we suggest that more
      studies be conducted on the pediatric group.

PMID- 23878567
TI  - Incidence and risk factors of functional upper airway complications of primary
      esthetic closed rhinoplasty in two residency programs: A 6-month preliminary
      prospective cohort study.
AB  - BACKGROUND: Although esthetic rhinoplasty has many advantages, it might lead to
      some complications as well. The literature includes scarce and severely
      controversial studies on these issues, and there is no research on complications
      of cosmetic closed rhinoplasty. In addition, some complications are not assessed
      after any rhinoplasty types. Besides, there is no investigation on the outcome of
      rhinoplasty carried out by graduate students. The purpose of this study was to
      determine these. MATERIALS AND METHODS: In this preliminary prospective cohort
      study, 96 healthy patients underwent closed esthetic rhinoplasty by senior
      residents of otolaryngology and maxillofacial surgery at Taleghani Hospital
      (Tehran, 2004-2006). Afterward, at 11 follow-up sessions (the 1(st), 2(nd),
      3(rd), 4(th), 6(th), 8(th), 10(th), 12(th), 16(th), 20(th), and 24(th)
      postoperative weeks), five functional complications (hyposmia/anosmia, nasal
      obstruction, unpleasant voice changes, recurrent colds, and synechiae) were
      questioned/examined. The presence of a symptom during at least four subsequent
      sessions (without elimination until the sixth postoperative month) and the
      appearance of synechiae in any session were regarded as positive. The data were
      assessed using Spearman's correlation coefficient (alpha = 0.05). RESULTS: The
      incidence rates of synechiae, nasal obstruction, unpleasant voice changes,
      hyposmia/anosmia, and recurrent colds were 56.25%, 37.5%, 0%, 1.04%, and 29.17%,
      respectively. No statistically significant relationship was found between the
      complications with age, gender, or the surgeon's specialty (P > 0.05), but the
      correlation with home care compliance was significant (rho = -0.29, P = 0.01).
      CONCLUSIONS: High complication rates were observed in both residency programs.
      Failure to follow home care instructions might prevent/delay recovery. Further in
      depth studies are needed to assess this.

PMID- 23878568
TI  - Shear bond strength of orthodontic buccal tubes to porcelain.
AB  - BACKGROUND: Bonding of molar tubes is becoming more popular in orthodontics.
      Occasionally, these bonding are done on posterior porcelain crowns or bridges.
      The purpose of this study was to evaluate the shear bond strength of buccal tubes
      on feldspathic porcelain crowns with two different methods. MATERIALS AND
      METHODS: Forty porcelain right molar crowns were fabricated for this study. The
      crowns were randomly divided into two groups. In group 1, the crowns were etched
      with 9.6% hydrofluoric acid, silane coupling agent applied, coated with bonding
      primer and bonded with Transbond XT (3M Unitek, Monrovia, Calif). In group 2, the
      crowns were etched with phosphoric acid 37%, silane coupling agent applied,
      coated with bonding primer and bonded with Transbond XT. All the crowns were
      stored for 24 hours at 37 degrees C and thermo-cycled before the shear bond test.
      The analysis of variance (ANOVA) was used to determine whether significant
      difference were present between the groups. RESULTS: The results of the analysis
      of variance (F = 0.23) indicated the shear bond strength of group 1 (3.57 +/-
      0.87 MPa) was not significantly different (P > 0.05) from group 2 (3.46 +/- 0.65
      Mpa). Fisher's exact test for the adhesive remnant index (ARI) revealed
      significant difference between both groups (P < 0.05). Eighty percent of group 1
      buccal tubes failed at buccal tube/resin interface and eighty percent of group 2
      mostly failed at porcelain/resin interface. CONCLUSION: Etching with phosphoric
      acid with the use of silane coupling agent would be safer and should make it
      easier for clinicians to clean the adhesive on the porcelain surface after
      debonding.

PMID- 23878569
TI  - Evaluation of the influence of blood glucose level on oral candidal colonization
      in complete denture wearers with Type-II Diabetes Mellitus: An in vivo Study.
AB  - BACKGROUND: Candidal colonization in complete denture wearers is a commonly
      encountered condition that worsens in the presence of untreated Diabetes
      Mellitus. The aim of this study was to evaluate the correlation between oral
      candidiasis in denture-bearing mucosa and elevated blood glucose levels in
      complete denture wearers and to evaluate the effect of oral hypoglycemic drug
      therapy in controlling oral candidal colonization in denture-bearing mucosa of
      complete denture wearers with Type II Diabetes Mellitus. MATERIALS AND METHODS:
      This prospective observational study involved the participation of 15 complete
      denture wearers with Type II Diabetes Mellitus. The sample collection was made
      prior and after oral hypoglycaemic drug intervention, by swabbing the rugal
      surfaces of palatal mucosa, cultured and the density of the candidal colony
      formed was analyzed and interpreted as colony forming units (CFU) per mL. The
      candidal samples CFU and corresponding pre- and post-prandial blood glucose
      levels were estimated, analyzed and compared using Karl Pearson correlation
      analysis and paired t-test (alpha = 0.05). RESULTS: The Karl Pearson correlation
      analysis showed that there was a positive correlation between the blood glucose
      levels (PPS and FBS) and the candidal colonization (CFU) (P < 0.05). The mean
      values of all the variables were analyzed using the paired t-test. There was
      significant reduction in the mean values of blood glucose levels (P < 0.001) and
      the mean values of the CFU (P < 0.001) following oral hypoglycemic drug therapy.
      CONCLUSION: Positive correlation was observed between oral candidiasis in
      complete denture-bearing mucosa and elevated blood glucose levels and oral
      hypoglycemic drug therapy has a positive effect in controlling oral candidal
      colonization in complete denture wearers with Type II Diabetes Mellitus.

PMID- 23878570
TI  - Sialolipoma of salivary glands: Two case reports and review of the literature.
AB  - Sialolipoma is a rare neoplasm of salivary glands, described as a distinct entity
      by Nagao et al. in 2001. Thirty-six cases of sialolipoma in minor and major
      salivary glands have been reported thus far in addition to the two new cases of
      sialolipoma arising in the major salivary glands in this study. Thirty-six cases
      of sialolipoma published in English language reports were analyzed considering
      gender, age, location, size, duration of symptoms, treatment mode, follow-up, and
      histologic findings. Congenital sialolipomas were considered in this study. The
      first case occurred in a 45-year-old female and presented as a localized swelling
      in right parotid area. The second case occurred in an 18-year-old female as a
      swelling in the left parotid region. On histopathological examination, these
      lesions were diagnosed as sialolipoma. 

PMID- 23878571
TI  - Minimal guided bone regeneration procedure for immediate implant placement in the
      esthetic zone.
AB  - The anterior maxilla presents a challenging milieu interior for ideal placement
      of implants because of the compromised bone quality. With the advent of intraoral
      bone harvesting and augmentation techniques, immediate implant placement into
      fresh extraction sockets have become more predictable. Immediate implant
      placement has numerous advantages compared to the delayed procedure including
      superior esthetic and functional outcomes, maintenance of soft and hard tissue
      integrity and increased patient compliance. This case report exhibits immediate
      implant placement in the maxillary esthetic zone by combining a minimal invasive
      autogenous block bone graft harvest technique for ensuring successful
      osseointegration of the implant at the extraction site. 

PMID- 23878572
TI  - Dentinoameloblastoma with ghost cells: A rare case report with emphasis on its
      biological behavior.
AB  - Ameloblastomas are regarded as a homogeneous group of neoplasms with locally
      invasive character. They generally do not show induction of dental hard tissue
      formation except in few cases. Biological behavior and histogenesis of these
      tumors is still unexplored as there is lack of relevant studies and long follow
      up of these patients. So, we aimed to report this rare case of
      dentinoameloblastoma with unique presence of ghost cells in middle-aged female
      involving maxilla with emphasis on its biological behavior. We conclude that
      although histogenesis of this tumor is not clear but biological potential is
      similar to conventional ameloblastoma requiring wider excision. 

PMID- 23878573
TI  - Progressive hemifacial atrophy.
AB  - Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an
      uncommon degenerative and poorly understood condition. It is characterized by a
      slow and progressive but self-limited atrophy affecting one side of the face. The
      incidence and the cause of this alteration are unknown. A cerebral disturbance of
      fat metabolism has been proposed as a primary cause. Possible factors that are
      involved in the pathogenesis include trauma, viral infections, heredity,
      endocrine disturbances and auto-immunity. The most common complications that
      appear in association to this disorder are: trigeminal neuralgia, facial
      paresthesia, severe headache and epilepsy. Characteristically, the atrophy
      progresses slowly for several years and, it becomes stable. The objective of this
      work is, through the presentation of a clinical case, to accomplish a literature
      review concerning general characteristics, etiology, physiopathology and
      treatment of progressive hemifacial atrophy. 

PMID- 23878574
TI  - Ameloblastic fibrosarcoma of the upper jaw: Report of a rare case with long-term
      follow-up.
AB  - Ameloblastic fibrosarcoma (AFS) is a rare malignant mixed odontogenic tumor which
      is usually considered as the malignant counterpart of ameloblastic fibroma. Only
      mesenchymal component represents sarcomatous alterations and ameloblast-like
      epithelial nest remains bland in AFS. Here, we report a case of AFS in a 26-year
      old man in the maxilla, which was regarded as an uncommon location for this
      tumor. After 2 years follow up, no evidence of recurrence was noted. We also
      emphasize on comprehensive clinical, radiographic, and histopathologic evaluation
      of such patients rather than immunohistochemical staining to make an accurate
      diagnosis. 

PMID- 23878575
TI  - Snus (nass) and oral cancer: A case series report.
AB  - Snus (nass) is a form of snuff used in a similar manner to American dipping
      tobacco, but it does not typically result in a need for spitting. Possible
      hazards associated with this material include malignant and premalignant lesions
      in the oral cavity and gastrointestinal tract. The use of smokeless tobacco has
      increased in the Middle East in recent decades, particularly among teenagers and
      young adults. Therefore, practitioners must be able to recognize malignant and
      premalignant lesions. Although, an estimated 10-25% of the world's population
      uses smokeless tobacco, this practice is virtually unknown in Iran. The aim of
      this study is to report a series of cases of squamous cell carcinoma and
      verrucous carcinoma occurring in the users of snus, who referred to the
      Department of Oral Medicine in Kerman Dental School. 

PMID- 23878576
TI  - Central cementifying fibroma of maxilla.
AB  - Central cementifying fibroma is a bony tumor, which is believed to be derived
      from the cells of the periodontal ligament. Central cemento-ossifying fibroma
      behaves like, a benign bone neoplasm. This bone tumor consists of highly
      cellular, fibrous tissue that contains varying amounts of calcified tissue
      resembling bone, cementum, or both. Central cemento-ossifying fibromas of the
      mandible are common; however, they are rare in the maxilla region. This tumor is
      most frequent between 35 and 40 years of ages. In this report we have described a
      37-year-old male with cemento-ossifying fibroma of the maxilla region with the
      mass that had been appeared 2-3 months prior to his first referral. Radiologic
      imaging such as intra-oral, panoramic, and Cone Beam CT had been performed.
      Histological analysis was done and finally diagnosis of central cementifying
      fibroma was made. The postoperative follow up at 12 months revealed no
      recurrence. 

PMID- 23878577
TI  - All-ceramic prosthetic rehabilitation of a worn dentition: Use of a distal
      cantilever. Two-year follow-up.
AB  - The rehabilitation of heavily abraded occlusion in patients with parafunctional
      habits is a restorative challenge to the dentist. Use of all-ceramic systems in
      such cases is widely considered, but uncertainty over their resistance hinders
      their broad use. The authors would like to illustrate a possible approach by
      mixing two all-ceramic systems based on zirconium dioxide and lithium disilicate.
      A 48-year-old female patient attended with reduced vertical dimension in a full
      dentition. She suffered from craniomandibular (CMD) pain and desired an esthetic
      rehabilitation. Prosthodontic treatment was started in a pain-free condition,
      after correction of the vertical dimension with an occlusal splint, over four
      months. Determination of the treatment was based on the clinical findings: IPS
      e.max((r)) ZirCAD frameworks veneered with IPS e.max((r)) Ceram were used for
      discolored retainers or subgingival finishing lines. All the rest received IPS
      e.max((r)) Press crowns. A zirconia-based, single-tooth-retained distal
      cantilever reconstruction was used to replace a missing second molar. No
      technical or biological complication was observed 24 months after treatment. The
      patient was highly satisfied and pain-free. 

PMID- 23878578
TI  - C-shaped root canal.

PMID- 23878579
TI  - Status of Oro-Dental health problems and treatment needs among urban population
      of South-West Delhi.

PMID- 23878581
TI  - Collagen XVII: a shared antigen in neurodermatological interactions?
AB  - Collagen XVII is a nonfibril-forming transmembrane collagen, which functions as
      both a matrix protein and a cell-surface receptor. It is particularly copious in
      the skin, where it is known to be a structural component of hemidesmosomes. In
      addition, collagen XVII has been found to be present in the central nervous
      system, thus offering an explanation for the statistical association between
      bullous pemphigoid, in which autoimmunity is directed against dermal collagen
      XVII, and neurological diseases. In support of the hypothesis that collagen XVII
      serves as a shared antigen mediating an immune response between skin and brain,
      research on animal and human tissue, as well as numerous epidemiological and case
      studies, is presented. 

PMID- 23878583
TI  - Human monoclonal antibody-based therapy in the treatment of invasive candidiasis.
AB  - Invasive candidiasis (IC) represents the leading fungal infection of humans
      causing life-threatening disease in immunosuppressed and neutropenic individuals
      including also the intensive care unit patients. Despite progress in recent years
      in drugs development for the treatment of IC, morbidity and mortality rates still
      remain very high. Historically, cell-mediated immunity and innate immunity are
      considered to be the most important lines of defense against candidiasis.
      Nevertheless recent evidence demonstrates that antibodies with defined
      specificities could act with different degrees showing protection against
      systemic and mucosal candidiasis. Mycograb is a human recombinant monoclonal
      antibody against heat shock protein 90 (Hsp90) that was revealed to have synergy
      when combined with fluconazole, caspofungin, and amphotericin B against a broad
      spectrum of Candida species. Furthermore, recent studies have established an
      important role for Hsp90 in mediating Candida resistance to echinocandins, giving
      to this antibody molecule even more attractive biological properties. In response
      to the failure of marketing authorization by the CHMP (Committee for Medicinal
      Products for Human Use) a new formulation of Mycograb, named Mycograb C28Y
      variant, with an amino acid substitution was developed in recent years. First
      data on Mycograb C28Y variant indicate that this monoclonal antibody lacked
      efficacy in a murine candidiasis model. 

PMID- 23878582
TI  - The leech nervous system: a valuable model to study the microglia involvement in
      regenerative processes.
AB  - Microglia are intrinsic components of the central nervous system (CNS). During
      pathologies in mammals, inflammatory processes implicate the resident microglia
      and the infiltration of blood cells including macrophages. Functions of microglia
      appear to be complex as they exhibit both neuroprotective and neurotoxic effects
      during neuropathological conditions in vivo and in vitro. The medicinal leech
      Hirudo medicinalis is a well-known model in neurobiology due to its ability to
      naturally repair its CNS following injury. Considering the low infiltration of
      blood cells in this process, the leech CNS is studied to specify the activation
      mechanisms of only resident microglial cells. The microglia recruitment is known
      to be essential for the usual sprouting of injured axons and does not require any
      other glial cells. The present review will describe the questions which are
      addressed to understand the nerve repair. They will discuss the implication of
      leech factors in the microglial accumulation, the identification of nerve cells
      producing these molecules, and the study of different microglial subsets. Those
      questions aim to better understand the mechanisms of microglial cell recruitment
      and their crosstalk with damaged neurons. The study of this dialog is necessary
      to elucidate the balance of the inflammation leading to the leech CNS repair. 

PMID- 23878586
TI  - Increased risk of RSV infection in children with Down's syndrome: clinical
      implementation of prophylaxis in the European Union.
AB  - Prospective cohort studies show that Down's syndrome (DS) is an independent risk
      factor for hospitalization for RSV bronchiolitis. It is unknown whether this
      observation has been translated into specific management for DS children. The
      primary goal was to assess the knowledge of healthcare providers in the European
      Union about RSV infection in DS children and to determine whether it influenced
      the implementation of prophylaxis. DS caregivers were surveyed using a
      standardized questionnaire, and country-specific guidelines were obtained. Fifty
      three caregivers participated. Thirty-nine (86.7%) had knowledge of the increased
      risk of severe RSV infection in DS children, and 30 (71.4%) graded that it was
      important to have a statement on the use of RSV prophylaxis in existing
      guidelines. Twenty-eight participants had a local DS guideline; hard copies of
      twelve unique guidelines were obtained. Only one (8.3%) contained a statement on
      RSV prophylaxis for DS, and five considered such a statement for the next
      version. Conclusion. Most pediatricians had knowledge that DS children have an
      increased risk of severe RSV infection. Despite the lack of a specific RSV
      prophylaxis trial in DS, they felt that a statement on RSV prophylaxis in DS
      guidelines was important, but this was rarely present in current guidelines. 

PMID- 23878584
TI  - Peptide-based vaccinology: experimental and computational approaches to target
      hypervariable viruses through the fine characterization of protective epitopes
      recognized by monoclonal antibodies and the identification of T-cell-activating
      peptides.
AB  - Defining immunogenic domains of viral proteins capable of eliciting a protective
      immune response is crucial in the development of novel epitope-based prophylactic
      strategies. This is particularly important for the selective targeting of
      conserved regions shared among hypervariable viruses. Studying postinfection and
      postimmunization sera, as well as cloning and characterization of monoclonal
      antibodies (mAbs), still represents the best approach to identify protective
      epitopes. In particular, a protective mAb directed against conserved regions can
      play a key role in immunogen design and in human therapy as well. Experimental
      approaches aiming to characterize protective mAb epitopes or to identify T-cell
      activating peptides are often burdened by technical limitations and can require
      long time to be correctly addressed. Thus, in the last decade many epitope
      predictive algorithms have been developed. These algorithms are continually
      evolving, and their use to address the empirical research is widely increasing.
      Here, we review several strategies based on experimental techniques alone or
      addressed by in silico analysis that are frequently used to predict immunogens to
      be included in novel epitope-based vaccine approaches. We will list the main
      strategies aiming to design a new vaccine preparation conferring the protection
      of a neutralizing mAb combined with an effective cell-mediated response. 

PMID- 23878587
TI  - JC polyomavirus (JCV) and monoclonal antibodies: friends or potential foes?
AB  - Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of
      the central nervous system (CNS), observed in immunodeficient patients and caused
      by JC virus ((JCV), also called JC polyomavirus (JCPyV)). After the HIV pandemic
      and the introduction of immunomodulatory therapy, the PML incidence significantly
      increased. The correlation between the use of natalizumab, a drug used in
      multiple sclerosis (MS), and the PML development of particular relevance. The
      high incidence of PML in natalizumab-treated patients has highlighted the
      importance of two factors: the need of PML risk stratification among natalizumab
      treated patients and the need of effective therapeutic options. In this review,
      we discuss these two needs under the light of the major viral models of PML
      etiopathogenesis. 

PMID- 23878588
TI  - Obesity, cancer, and acetyl-CoA metabolism.
AB  - As rates of obesity soar in the Unites States and around the world, cancer
      attributed to obesity has emerged as major threat to public health. The link
      between obesity and cancer can be attributed in part to the state of chronic
      inflammation that develops in obesity. Acetyl-CoA production and protein
      acetylation patterns are highly sensitive to metabolic state and are
      significantly altered in obesity. In this article, we explore the potential role
      of nutrient-sensitive lysine acetylation in regulating inflammatory processes in
      obesity-linked cancer.

PMID- 23878589
TI  - Baicalin's Therapeutic Time Window of Neuroprotection during Transient Focal
      Cerebral Ischemia and Its Antioxidative Effects In Vitro and In Vivo.
AB  - We investigated the effects of baicalin on an ischemia-reperfusion-induced brain
      injury model in rats and its antioxidative activities in vitro and in vivo. An
      ischemia-reperfusion injury of the brain via a middle cerebral artery occlusion
      (MCAO) was induced in rats. Baicalin was injected at different time points (0, 2,
      4, and 6 h) after the MCAO was induced. Baicalin can improve neurological
      function and significantly decrease brain infarction within a time window of 4 h.
      Moreover, baicalin was able to reduce cell apoptosis and had the strong
      antioxidative effect of reducing reactive oxygen species production and
      malondialdehyde generation. In contrast, baicalin interfered with superoxide
      dismutase and nicotinamide adenine dinucleotide 2'-phosphate oxidase activities.
      Moreover, baicalin also exhibited strong neuroprotective effects against H2O2
      mediated injury and improved the SOD activity of neurons. Furthermore, baicalin
      demonstrated good scavenging of hydroxyl radicals, superoxide anions, and DPPH
      radicals and exerted an additional effect of inhibiting xanthine oxidase.
      Baicalin showed beneficial effects against MCAO-induced injury within a 4 h time
      window, and its antioxidative effects both in vitro and in vivo may partly
      elucidate its mechanism of action. 

PMID- 23878590
TI  - Flavonoids induce the synthesis and secretion of neurotrophic factors in cultured
      rat astrocytes: a signaling response mediated by estrogen receptor.
AB  - Neurotrophic factors are playing vital roles in survival, growth, and function of
      neurons. Regulation of neurotrophic factors in the brain has been considered as
      one of the targets in developing drug or therapy against neuronal disorders.
      Flavonoids, a family of multifunctional natural compounds, are well known for
      their neuronal beneficial effects. Here, the effects of flavonoids on regulating
      neurotrophic factors were analyzed in cultured rat astrocytes. Astrocyte is a
      major secreting source of neurotrophic factors in the brain. Thirty-three
      flavonoids were screened in the cultures, and calycosin, isorhamnetin, luteolin,
      and genistein were identified to be highly active in inducing the synthesis and
      secretion of neurotrophic factors, including nerve growth factor (NGF), glial
      derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF).
      The inductions were in time- and dose-dependent manners. In cultured astrocytes,
      the phosphorylation of estrogen receptor was triggered by application of
      flavonoids. The phosphorylation was blocked by an inhibitor of estrogen receptor,
      which in parallel reduced the flavonoid-induced expression of neurotrophic
      factors. The results proposed the role of flavonoids in protecting brain
      diseases, and therefore these flavonoids could be developed for health food
      supplement for patients suffering from neurodegenerative diseases. 

PMID- 23878591
TI  - Study on the dynamic compound structure composed of mast cells, blood vessels,
      and nerves in rat acupoint.
AB  - Background. Circulation system, immunity system, and nervous system have a close
      relationship with meridian phenomen. However, there is still lack of the results
      of dynamic changes of these structures in acupoint. The aim of this study is to
      explore the interrelationship by composite staining techniques.
      Methodology/Principal Findings. Twenty rats were separated into
      electroacupuncture group (EA) and control group (Con) randomly. In EA group, the
      Zusanli and Weishu were stimulated with the 0.1 mA for 25 min. The tissue of
      these acupoints was double-stained with acetylcholinesterase and Toluidine blue.
      The compound structure of mast cells, nervous fibers, and mast cells in the
      acupoint was observed. Conclusions/Significance. The blood vessels, mast cells
      and acetylcholinesterase responded nerves were clearly observed in acupoint
      tissues. EA can result in the mast cell recruitment and migration along the blood
      vessels and nervous bundle, which conformed the dynamic compound structure and
      played important roles in acupuncture. 

PMID- 23878592
TI  - BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell
      Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells.
AB  - For many malignancies, radiation therapy remains the second option only to
      surgery in terms of its curative potential. However, radiation-induced tumor cell
      death is limited by a number of factors, including the adverse response of the
      tumor microenvironment to the treatment and either intrinsic or acquired
      mechanisms of evasive resistance, and the existence of cancer stem cells (CSCs).
      In this study, we demonstrated that using different doses of irradiation led to
      the enrichment of CD133(+) Mahlavu cells using flow cytometric method.
      Subsequently, CD133(+) Mahlavu cells enriched by irradiation were characterized
      for their stemness gene expression, self-renewal, migration/invasion abilities,
      and radiation resistance. Having established irradiation-enriched CD133(+)
      Mahlavu cells with CSC properties, we evaluated a phytochemical, pterostilbene
      (PT), found abundantly in blueberries, against irradiation-enriched CSCs. It was
      shown that PT treatment dose-dependently reduced the enrichment of CD133(+)
      Mahlavu cells upon irradiation; PT treatment also prevented tumor sphere
      formation, reduced stemness gene expression, and suppressed invasion and
      migration abilities as well as increasing apoptosis of CD133(+) Mahlavu CSCs.
      Based on our experimental data, pterostilbene could be used to prevent the
      enrichment of CD133(+) hepatoma CSCs and should be considered for future clinical
      testing as a combined agent for HCC patients. 

PMID- 23878593
TI  - Chinese herbal medicine qi ju di huang wan for the treatment of essential
      hypertension: a systematic review of randomized controlled trials.
AB  - Background. Chinese herbs are potentially effective for hypertension. Qi Ju Di
      Huang Wan (QJDHW) is a commonly used Chinese herbal medicine as a monotherapy or
      in combination with other antihypertensive agents for the treatment of essential
      hypertension (EH). However, there is no critically appraised evidence such as
      systematic reviews or meta-analyses on the effectiveness and safety of QJDHW for
      EH. Methods and Findings. CENTRAL, PubMed, CBM, CNKI, VIP, and online clinical
      trial registry websites were searched for published and unpublished randomized
      controlled trials (RCTs) of QJDHW for essential hypertension up to January 2013
      with no language restrictions. A total of 10 randomized trials involving 1024
      patients were included. Meta-analysis showed that QJDHW combined with
      antihypertensive drugs was more effective in lowering blood pressure and
      improving TCM syndrome for the treatment of essential hypertension than
      antihypertensive drugs used alone. No trials reported severe adverse events
      related to QJDHW. Conclusions. Our review suggests that QJDHW combined with
      antihypertensive drugs might be an effective treatment for lowering blood
      pressure and improving symptoms in patients with essential hypertension. However,
      the finding should be interpreted with caution because of the poor methodological
      quality of included trials. There is an urgent need for well-designed, long-term
      studies to assess the effectiveness of QJDHW in the treatment of essential
      hypertension. 

PMID- 23878595
TI  - Which approach is more effective in the selection of plants with antimicrobial
      activity?
AB  - The development of the present study was based on selections using random, direct
      ethnopharmacological, and indirect ethnopharmacological approaches, aiming to
      evaluate which method is the best for bioprospecting new antimicrobial plant
      drugs. A crude extract of 53 species of herbaceous plants collected in the
      semiarid region of Northeast Brazil was tested against 11 microorganisms. Well
      agar diffusion and minimum inhibitory concentration (MIC) techniques were used.
      Ten extracts from direct, six from random, and three from indirect
      ethnopharmacological selections exhibited activities that ranged from weak to
      very active against the organisms tested. The strain most susceptible to the
      evaluated extracts was Staphylococcus aureus. The MIC analysis revealed the best
      result for the direct ethnopharmacological approach, considering that some
      species yielded extracts classified as active or moderately active (MICs between
      250 and 1000 ug/mL). Furthermore, one species from this approach inhibited the
      growth of the three Candida strains. Thus, it was concluded that the direct
      ethnopharmacological approach is the most effective when selecting species for
      bioprospecting new plant drugs with antimicrobial activities. 

PMID- 23878594
TI  - Trends in the treatment of hypertension from the perspective of traditional
      chinese medicine.
AB  - Hypertension is a major public-health issue. Much consensus has been reached in
      the treatment, and considerable progress has been made in the field of
      antihypertensive drugs. However, the standard-reaching rate of blood pressure is
      far from satisfaction. Considering these data and the seriousness of the effects
      of hypertension on the individual and society as a whole, both economically and
      socially, physicians must look for more effective and alternative ways to achieve
      the target blood pressure. Could treatment of hypertension be improved by
      insights from traditional Chinese medicine? As one of the most important parts in
      complementary and alternative therapies, TCM is regularly advocated for lowering
      elevated blood pressure. Due to the different understanding of the pathogenesis
      of hypertension between ancient and modern times, new understanding and treatment
      of hypertension need to be reexplored. Aiming to improve the efficacy of Chinese
      herbal medicine in treating hypertension, the basis of treatment is explored
      through systematically analyzing the literature available in both English and
      Chinese search engines. This paper systematically reviews the trends in emerging
      therapeutic strategies for hypertension from the perspective of traditional
      Chinese medicine. 

PMID- 23878597
TI  - The Expression of CD14(+)CD16(+) Monocyte Subpopulation in Coronary Heart Disease
      Patients with Blood Stasis Syndrome.
AB  - Blood stasis syndrome (BSS), a comprehensive pathological state, is one of the
      traditional Chinese medicine syndromes of coronary heart disease (CHD). In our
      previous study, we investigated that Fc gamma RIIIA (also called CD14(+)CD16(+)
      monocyte subpopulation) is one of the differentially expressed genes related to
      CHD patients and its possible role in the atherosclerotic formation and plaque
      rupture. However, whether or not the deregulation of CD14(+)CD16(+) monocyte
      subpopulation expression is implicated in the pathogenesis of CHD patients with
      BSS has not yet been elucidated. In this study, we found that there was no
      significant difference between CHD patients with BSS and non-BSS in
      CD14(+)CD16(+) monocyte subpopulation at gene level. Moreover, the protein level
      of CD14(+)CD16(+) monocyte subpopulation in CHD patients with BSS was increased
      significantly when compared to the CHD patients with non-BSS. Additionally, the
      level of inflammatory cytokines downstream of CD14(+)CD16(+) monocyte
      subpopulation such as TNF- alpha and IL-1 in sera was much higher in CHD patients
      with BSS than that in CHD patients with non-BSS. Taken together, these results
      indicated that CD14(+)CD16(+) monocyte subpopulation was implicated in the
      pathogenesis of CHD patients with BSS, which may be one of the bases of the
      essence of BSS investigation. 

PMID- 23878596
TI  - Electroacupuncture Attenuates 5'-Guanidinonaltrindole-Evoked Scratching and
      Spinal c-Fos Expression in the Mouse.
AB  - The present study was undertaken to investigate the influence of
      electroacupuncture (EA) on compulsive scratching in mice and c-Fos expression
      elicited by subcutaneous (s.c.) administration of a known puritogen, 5'
      guanidinonaltrindole (GNTI) to the neck. Application of EA to Hegu (LI4) and
      Quchi (LI11) acupoints at 2 Hz, but not 100 Hz, attenuated GNTI-evoked
      scratching. In mice pretreated with the u opioid receptor antagonist naloxone, EA
      2 Hz did not attenuate GNTI-evoked scratching, whereas EA at 2 Hz did attenuate
      GNTI-evoked scratching in mice pretreated with the kappa opioid receptor
      antagonist nor-binaltorphimine. Moreover, intradermal (i.d.) administration of
      the selective u opioid receptor agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin
      acetate (DAMGO) attenuated GNTI-evoked scratching behavior, while s.c.
      administration of DAMGO was ineffective. GNTI provoked c-Fos expression on the
      lateral side of the superficial layer of the dorsal horn of the cervical spinal
      cord. Application of 2 Hz EA to LI4 and LI11 decreased the number of c-Fos
      positive nuclei induced by GNTI. It may be concluded that application of 2 Hz EA
      to LI4 and LI11 attenuates scratching behavior induced by GNTI in mice and that
      the peripheral u opioid system is involved, at least in part, in the anti
      pruritic effects of EA. 

PMID- 23878598
TI  - Timosaponin AIII Suppresses Hepatocyte Growth Factor-Induced Invasive Activity
      through Sustained ERK Activation in Breast Cancer MDA-MB-231 Cells.
AB  - Background. The aim of this study was to investigate the mechanisms by which
      Timosaponin AIII (TAIII) is able to inhibit HGF-induced invasion activity in the
      triple negative breast cancer cell line MDA-MB-231. Methods. After pretreatment
      with different concentrations (10(-6)~10(-8) M) of TAIII, the cells were treated
      with hepatocyte growth factor (HGF, 15 ng/mL). At different time intervals after
      coincubation, various parameters, including the expression of c-Met, ERK, COX2,
      and MMP-9, which were assessed by Western blotting or by real-time PCR, were
      analyzed. In addition, invasive activity was also monitored. Results. HGF was
      found to induce c-MET activation and ERK activation, together with increased COX2
      protein expression; these changes were followed by a subsequent increase in
      invasive activity. TAIII was found to suppress HGF-induced invasive activity and
      COX2 gene expression in a concentration-dependent manner (10(-6)~10(-8) M) in
      parallel with increases in the phosphoforms of c-Met and ERK after TAIII
      treatment. The mechanisms by which TAIII suppresses HGF-induced invasive activity
      were demonstrated to include sustained cytoplasmic and nuclear ERK activation;
      these led to a suppression of nuclear ATF2 activation, which was followed by
      downregulation of COX2 and MMP-9 transcription. Conclusion. TAIII suppresses HGF
      induced invasive activity in MDA-MB-231 cells via sustained ERK activation. 

PMID- 23878599
TI  - Chinese herbal medicine for the treatment of prehypertension.
AB  - Objectives. To assess the current clinical evidence of Chinese herbal medicine
      (CHM) for prehypertension. Search Strategy. Electronic databases were searched
      until May, 2013. Inclusion Criteria. We included randomized clinical trials
      testing CHM against life style intervention and no treatment, or combined with
      life style intervention against life style intervention. Data Extraction and
      Analyses. Study selection, data extraction, quality assessment, and data analyses
      were conducted according to Cochrane standards. Results. Five trials were
      included. Methodological quality of the trials was evaluated as generally low.
      Only 1 trial reported allocation sequence. No trial reported the allocation
      concealment, double blinding, placebo control, presample size estimation,
      intention to treat analysis, and drop-out. All the included trials were not
      multicenter and large scale. Although meta-analysis showed that CHM is superior
      to either life style intervention group or no treatment group in decreasing blood
      pressure, we are unable to draw a definite conclusion on the effect of CHM due to
      the poor research methods used in the reviewed trials. The safety of CHM is still
      uncertain. Conclusions. There is no evidence to show that CHM is effective and
      safe for prehypertension due to serious methodological flaw of the reviewed
      trials. Rigorously designed trials are warranted to confirm these results. 

PMID- 23878600
TI  - Hu-Lu-Ba-Wan Attenuates Diabetic Nephropathy in Type 2 Diabetic Rats through PKC-
      alpha /NADPH Oxidase Signaling Pathway.
AB  - Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney
      deficiency. The aim of this study was to explore the effect and mechanism of HLBW
      on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was
      established by being fed a high-fat diet and intravenous injection of
      streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose
      level, lipid profile, renal function, 24-hour total urinary protein, and albumin
      content were examined. Renal morphology and superoxide anion levels were
      evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH)
      and protein kinase C-alpha (PKC- alpha ) related genes expression in renal tissue
      were also determined. Our data demonstrated that HLBW significantly improved
      hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with
      those of control group. HLBW also alleviated glomerular expansion and fibrosis,
      extracellular matrix accumulation and effacement of the foot processes.
      Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the
      protein and mRNA expressions of p47(phox), and the protein expression of
      phosphorylated PKC- alpha in renal tissue. These results suggest that HLBW is
      effective in the treatment of DN in rats. The underlying mechanism may be related
      to the attenuation of renal oxidative stress via PKC- alpha /NADPH oxidase
      signaling pathway. 

PMID- 23878601
TI  - Regulation of DDAH1 as a Potential Therapeutic Target for Treating Cardiovascular
      Diseases.
AB  - Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase
      inhibitor that blocks nitric oxide production, while congestive heart failure is
      associated with increased plasma and tissue ADMA content. Increased plasma ADMA
      is a strong and independent predictor of all-cause mortality in the community and
      the strongest predictor of mortality in patients after myocardial infarction.
      Recent studies demonstrated that dimethylarginine dimethylaminohydrolase-1
      (DDAH1) is the critical enzyme for ADMA degradation and thereby plays an
      important role in maintaining cardiovascular nitric oxide bioavailability.
      Interestingly, activation of the farnesoid X receptor (FXR) through the bile acid
      ursodeoxycholic acid (UDCA) or synthetic FXR agonists, such as GW4064, can
      increase DDAH1 expression. Thus, modulating DDAH1 activity through FXR receptor
      agonists such as UDCA could be a therapeutic target for treating reduced nitric
      oxide bioavailability in congestive heart failure and other cardiovascular
      diseases. 

PMID- 23878602
TI  - Antitussive Activity of the Water-Extracted Carbohydrate Polymer from Terminalia
      chebula on Citric Acid-Induced Cough.
AB  - Terminalia chebula, a medicinal plant, is widely used in the management of
      various diseases. As the water extract of its dried ripe fruit is a frequently
      used preparation, we decided to look for bioactive polysaccharide in this
      extract. We demonstrate that the obtained polysaccharide fraction, CP, contained
      a highly branched arabinogalactan protein having a (1 -> 3)-, (1 -> 6)- and (1 ->
      3, 6)-linked beta -D-Galp together with (1 -> 5)- and (1 -> 3)-linked alpha -L
      Araf and nonreducing end units of alpha -L-Araf. This polymer possesses strong
      antitussive property. Our results showed that the number of citric acid-induced
      cough efforts decreased significantly after the oral application of
      polysaccharide fraction in a dose of 50 mg kg(-1) body weight. Its antitussive
      efficacy was higher than cough suppressive effect of standard drug codeine.
      Therefore, traditional aqueous extraction method provides a major polysaccharide,
      which induces a pharmacological effect: this could represent an attractive
      approach in phytotherapeutic managements. 

PMID- 23878603
TI  - A Review on Antihyperglycemic and Antihepatoprotective Activity of Eco-Friendly
      Punica granatum Peel Waste.
AB  - Over the past decade, pomegranate (Punica granatum) is entitled as a wonder fruit
      because of its voluminous pharmacological properties. In 1830, P. granatum fruit
      was first recognized in United States Pharmacopeia; the Philadelphia edition
      introduced the rind of the fruit, the New York edition the bark of the root and
      further 1890 edition the stem bark was introduced. There are significant efforts
      and progress made in establishing the pharmacological mechanisms of peel
      (pericarp or rind) and the individual constituents responsible for them. This
      review provides an insight on the phytochemical components that contribute too
      antihyperglycemic, hepatoprotective, antihyperlipidemic effect, and numerous
      other effects of wonderful, economic, and eco-friendly pomegranate peel extract
      (PP). 

PMID- 23878605
TI  - Study on the Formation of Novel Threadlike Structure through Intravenous
      Injection of Heparin in Rats and Refined Observation in Minipigs.
AB  - Objective. To study if the novel threadlike structure (NTS) was caused by
      coagulation during injecting urethane intraperitoneally and the source of NTS.
      Methods. Twenty-two SD rats were anaesthetized by urethane injected
      intraperitoneally. Heparin was injected at 5 minutes before the anaesthesia from
      femoral vein in 11 rats, and saline was given in the other 11 rats randomly. Six
      Chinese minipigs were carried to look for NTS. One sample was taken to be stained
      by DAPI/Phalloidin and observed by a laser scanning confocal microscope. Results.
      In the group of heparin, 10 rats were found to have NTS with appearance rate of
      90.9%, and 9 rats were found to have NTS with the appearance rate of 80.1%. Both
      groups have 1.81 average numbers of NTS in each rat without significant
      difference (P > 0.05). In the observation of pigs, the NTS was found to prolong
      from the serous membranes of abdominal wall and organ surface. Histological
      observation showed elongated nuclei and alignment which is similar to the
      characteristics of PVS. Conclusion. There is no strong evidence to say that the
      NTS on organ surface was caused by coagulation of blood. The source of NTS might
      be a prolonged structure from serous membrane in abdominal cavity during the
      development and more or less retained after birth. 

PMID- 23878604
TI  - Comparing Once- versus Twice-Weekly Yoga Classes for Chronic Low Back Pain in
      Predominantly Low Income Minorities: A Randomized Dosing Trial.
AB  - Background. Previous studies have demonstrated that once-weekly yoga classes are
      effective for chronic low back pain (cLBP) in white adults with high
      socioeconomic status. The comparative effectiveness of twice-weekly classes and
      generalizability to racially diverse low income populations are unknown. Methods.
      We conducted a 12-week randomized, parallel-group, dosing trial for 95 adults
      recruited from an urban safety-net hospital and five community health centers
      comparing once-weekly (n = 49) versus twice-weekly (n = 46) standardized yoga
      classes supplemented by home practice. Primary outcomes were change from baseline
      to 12 weeks in pain (11-point scale) and back-related function (23-point modified
      Roland-Morris Disability Questionnaire). Results. 82% of participants were
      nonwhite; 77% had annual household incomes <$40,000. The sample's baseline mean
      pain intensity [6.9 (SD 1.6)] and function [13.7 (SD 5.0)] reflected moderate to
      severe back pain and impairment. Pain and back-related function improved within
      both groups (P < 0.001). However, there were no differences between once-weekly
      and twice-weekly groups for pain reduction [-2.1 (95% CI -2.9, -1.3) versus -2.4
      (95% CI -3.1, -1.8), P = 0.62] or back-related function [-5.1 (95% CI -7.0, -3.2)
      versus -4.9 (95% CI -6.5, -3.3), P = 0.83]. Conclusions. Twelve weeks of once
      weekly or twice-weekly yoga classes were similarly effective for predominantly
      low income minority adults with moderate to severe chronic low back pain. This
      trial is registered with ClinicalTrials.gov NCT01761617. 

PMID- 23878606
TI  - Anti-Inflammatory, Anticholinesterase, and Antioxidant Potential of Scopoletin
      Isolated from Canarium patentinervium Miq. (Burseraceae Kunth).
AB  - Bioassay guided fractionation of an ethanol extract of leaves of Canarium
      patentinervium Miq. (Burseraceae Kunth.) led to the isolation of scopoletin. The
      structure of this coumarin was elucidated based on spectroscopic methods
      including nuclear magnetic resonance (NMR-1D and 2D) and mass spectrometry.
      Scopoletin inhibited the enzymatic activity of 5-lipoxygenase and acetyl
      cholinesterase with an IC50 equal to 1.76 +/- 0.01  MU M and 0.27 +/- 0.02 mM,
      respectively, and confronted oxidation in the ABTS, DPPH, FRAP, and beta 
      carotene bleaching assay with EC50 values equal to 5.62 +/- 0.03  MU M, 0.19 +/-
      0.01 mM, 0.25 +/- 0.03 mM and 0.65 +/- 0.07 mM, respectively. Given the
      aforementioned evidence, it is tempting to speculate that scopoletin represents
      an exciting scaffold from which to develop leads for treatment of
      neurodegenerative diseases. 

PMID- 23878607
TI  - Efficacy and safety of acupuncture in preterm and term infants.
AB  - The aim of the paper was to review the literature about safety and efficiency of
      acupuncture therapy in term and preterm infants. We searched Medline, EMBASE, and
      Cochrane Central Register of Controlled Trials using a predefined algorithm,
      reviewed abstracts from the Pediatric Academic Society annual meetings (2000
      2012), and performed a manual search of references in narrative and systematic
      reviews. A total of 26 studies identified met our search criteria. Only 6 of
      these studies met our inclusion criteria; however, two studies had to be excluded
      because the manuscripts were published in Chinese. Hence, only four studies were
      included in our analysis. Three of the four studies evaluated the effects of
      acupuncture on infantile colic, and one assessed pain reduction during minor
      painful procedures in preterm babies. The limited data available suggests that
      acupuncture could be a safe nonpharmacologic treatment option for pain reduction
      in term and preterm infants and could also be a non-pharmacologic treatment
      option to treat infantile colic. Currently acupuncture in infants should be
      limited to clinical trials and studies evaluating short- and long-term effects
      and should be performed only by practitioners with adequate training and
      experience in neonatal/pediatric acupuncture. 

PMID- 23878608
TI  - Apoptosis Induced by Tanshinone IIA and Cryptotanshinone Is Mediated by Distinct
      JAK/STAT3/5 and SHP1/2 Signaling in Chronic Myeloid Leukemia K562 Cells.
AB  - Though tanshinone IIA and cryptotanshinone possess a variety of biological
      effects such as anti-inflammatory, antioxidative, antimetabolic, and anticancer
      effects, the precise molecular targets or pathways responsible for anticancer
      activities of tanshinone IIA and cryptotanshinone in chronic myeloid leukemia
      (CML) still remain unclear. In the present study, we investigated the effect of
      tanshinone IIA and cryptotanshinone on the Janus activated kinase (JAK)/signal
      transducer and activator of transcription (STAT) signaling during apoptotic
      process. We found that both tanshinone IIA and cryptotanshinone induced apoptosis
      by activation of caspase-9/3 and Sub-G1 accumulation in K562 cells. However, they
      have the distinct JAK/STAT pathway, in which tanshinone IIA inhibits JAK2/STAT5
      signaling, whereas cryptotanshinone targets the JAK2/STAT3. In addition,
      tanshinone IIA enhanced the expression of both SHP-1 and -2, while
      cryptotanshinone regulated the expression of only SHP-1. Both tanshinone IIA and
      cryptotanshinone attenuated the expression of bcl-xL, survivin, and cyclin D1.
      Furthermore, tanshinone IIA augmented synergy with imatinib, a CML
      chemotherapeutic drug, better than cryptotanshinone in K562 cells. Overall, our
      findings suggest that the anticancer activity of tanshinone IIA and
      cryptotanshinone is mediated by the distinct the JAK/STAT3/5 and SHP1/2
      signaling, and tanshinone IIA has the potential for combination therapy with
      imatinib in K562 CML cells. 

PMID- 23878609
TI  - Inhibitory Effects of PC-SPESII Herbal Extract on Human Breast Cancer Metastasis.
AB  - Cancer metastasis is refractory to most forms of chemotherapy. Conventional and
      alternative drugs, such as Chinese herbal remedies, have been developed to target
      metastatic cancer cells. In this study, we investigated the effects of PC-SPESII,
      an herbal formulation, on the migration, invasion, and metastasis of an
      experimental human breast cancer cell line in vivo and in vitro. PC-SPESII
      suppressed pulmonary metastasis and tumor growth of MDA-MB-231 human breast
      cancer xenografts without affecting body weight, liver function, and kidney
      function. PC-SPESII also inhibited MDA-MB-231 cell migration and invasion in
      vitro in a dose-dependent manner. Based on ELISA analysis, secretion of MMP-2 and
      MMP-9, proteins associated with extracellular matrix degradation, was reduced in
      response to PC-SPESII treatment. Western blot analysis of whole-cell extracts
      revealed that the levels of proteolytic proteins associated with matrix and base
      membrane degradation (MMP-2, MMP-9, and uPA) were decreased and the levels of
      their endogenous inhibitors (TIMP1 and TIMP2) were increased. Moreover, the
      p38MAPK and SAPK/JNK signaling pathway, which stimulates proteolytic enzymes and
      matrix degradation, was inhibited by PC-PSESII. Remarkably, cotreatment with PC
      PSESII and p38MAPK or SAPK/JNK inhibitors magnified the antimetastatic phenotype.
      Our results indicate that PC-PSESII impairs human breast cancer metastasis by
      regulating proteolytic enzymes and matrix dynamics through the p38MAPK and
      SAPK/JNK pathway. 

PMID- 23878610
TI  - Evaluation of the Genotoxic Potential against H2O2-Radical-Mediated DNA Damage
      and Acute Oral Toxicity of Standardized Extract of Polyalthia longifolia Leaf.
AB  - Medicinal plants have been used in medicoculturally diverse countries around the
      world, where it is a part of a time-honoured tradition that is respected even
      today. Polyalthia longifolia leaf extract has been previously reported as an
      efficient antioxidant in vitro. Hence, the genotoxic effects of P. longifolia
      leaf were investigated by using plasmid relation, comet, and Allium cepa assay.
      In the presence of   (?) OH radicals, the DNA in supercoil was start nicked into
      open circular form, which is the product of the single-stranded cleavage of
      supercoil DNA and quantified as fragmented separate bands on agarose gel in
      plasmid relation assay. In the plasmid relation and comet assay, the P.
      longifolia leaf extract exhibited strong inhibitory effects against H2O2-mediated
      DNA damage. A dose-dependent increase of chromosome aberrations was also observed
      in the Allium cepa assay. The abnormalities scored were stickiness, c-mitosis,
      bridges, and vagrant chromosomes. Micronucleated cells were also observed at the
      interphase. The results of Allium cepa assay confirmed that the methanol extracts
      of P. longifolia exerted no significant genotoxic or mitodepressive effects at
      100  MU g/mL. Thus, this study demonstrated that P. longifolia leaf extract has a
      beneficial effect against oxidative DNA damage. This experiment is the first
      report for the protective effect of P. longifolia on DNA damage-induced by
      hydroxyl radicals. Additionally in acute oral toxicity study, female rats were
      treated at 5000 mg/kg body weight of P. longifolia leaf extract and observed for
      signs of toxicity for 14 days. P. longifolia leaf extract did not produce any
      treatment-related toxic effects in rats. 

PMID- 23878611
TI  - How Mental Illness is Perceived by Iranian Medical Students: A Preliminary Study.
AB  - The study aimed to assess medical students' attitudes toward mental illness
      following a 4-week psychiatry clerkship. All fifth-year medical students from
      three academic centers in Tehran were asked to participate in the study. They
      completed the questionnaire on the last day of their 4-week psychiatry clerkship.
      A self-administered questionnaire was used to examine participants' Attitudes
      Toward Mental Illness (ATMI). One hundred and sixty eight students completed the
      questionnaires (88.9% response rate). In general, the students had favorable
      attitudes toward mental illness at the end of their clerkship, with mean (+/- SD)
      ATMI total score of 78.6 (+/- 8.1) (neutral score, 66.0). The students showed the
      most favorable opinion (95.2%) about Category 5 (stereotypic attitude toward
      people with mental illness) whilst they revealed the least favorable opinion
      (64.3%) regarding Category 1 (social relations with people affected by mental
      illness). In addition, the students thought that movies were on the top of
      influential media on shaping the attitudes toward mental illness. Overall, most
      of Iranian medical students had generally favorable attitudes toward people with
      mental illness at the end of their clerkship. Therefore, it may be expected next
      generation of medical doctors show more favorable attitude toward mental illness.

PMID- 23878612
TI  - Alexithymia affects pre-hospital delay of patients with acute myocardial
      infarction: meta-analysis of existing studies.
AB  - BACKGROUND: The time between the onset of symptoms and reperfusion is a critical
      determinant of the clinical course of patients with acute myocardial infarction
      (AMI). Any delay in seeking help will affect patient's outcome. Alexithymia can
      influence the information processing but also the skills to detect the signal of
      an ongoing AMI. METHOD: Systematic review and meta-analysis of studies
      investigating the role of alexithymia in pre-hospital delay after AMI.
      Pubmed/Medline and PsychINFO/Ovid search from 1990 until 2012. RESULTS: Out of 29
      studies investigating the role of psychological factors in pre-hospital delay
      after AMI, 3 studies specifically assessed alexithymia, involving 258 patients.
      All studies used the Toronto Alexithymia Scale to group patients into clusters by
      time to presentation after AMI. Meta-analysis of data showed that the patients
      with higher emotional awareness (i.e., low alexithymia) had shorter time to
      presentation after AMI. CONCLUSIONS: Preliminary evidence indicates that
      alexithymia may have a role in seeking help delay after AMI. Further studies are
      necessary to better appreciate how alexithymia influence help-seeking in patients
      with an evolving AMI and in what extent their ineffective behavior can be
      changed.

PMID- 23878613
TI  - Epidemiology of early-onset dementia: a review of the literature.
AB  - Presenile Dementia or Early Onset Dementia (EOD) is a public health problem, it
      differs from Senile Dementia, and encloses a significant number of cases;
      nevertheless, it is still poorly understood and underdiagnosed. This study aims
      to review the prevalence and etiology of EOD, comparing EOD with Senile Dementia,
      as well as to show the main causes of EOD and their prevalence in population and
      non-population based studies. The computer-supported search used the following
      databases: Pubmed/Medline, ISI Web of Knowledge and Scielo. The search terms were
      alcohol-associated dementia, Alzheimer's disease, dementia, Creutzfeldt-jakob
      disease, dementia with lewy bodies, early onset dementia, frontotemporal lobar
      degeneration, Huntington's disease, mixed dementia, neurodegenerative disorders,
      Parkinson's disease dementia, presenile dementia, traumatic brain injury,
      vascular dementia. Only papers published in English and conducted from 1985 up to
      2012 were preferentially reviewed. Neurodegenerative diseases are the most common
      etiologies seen in EOD. Among the general population, the prevalence of EOD was
      found to range between 0 to 700 per 100.000 habitants in groups of 25-64 years
      old, with an increasing incidence with age. The progression of EOD was found to
      range between 8.3 to 22.8 new cases per 100.000 in those aged under 65 years.
      Alzheimer's disease (AD) is the major etiology, followed by Vascular Dementia
      (VaD) and Frontotemporal Lobar Degeneration (FTLD). A larger number of
      epidemiological studies to elucidate how environmental issues contribute to EOD
      are necessary, thus, we can collaborate in the planning and prevention of
      services toward dementia patients. 

PMID- 23878614
TI  - Self-esteem evaluation in children and adolescents suffering from ADHD.
AB  - BACKGROUND: Several recent studies investigated the relationship between self
      esteem and ADHD, however, the results are still controversial. In the present
      study we analyze the characteristics of self-esteem in a sample of children and
      adolescents suffering from ADHD, with a particular focus on the relationship
      between ADHD symptoms severity and treatment strategies. METHODS: A total of 85
      patients with ADHD (44 drug-free and 41 drug-treated, 23 of which atomoxetine
      treated and 18 Methylphenidate-treated) and 26 healthy controls were enrolled in
      the study in order to evaluate self-esteem using the Self-esteem Multidimensional
      Test (TMA). RESULTS: ADHD subjects revealed lower scores on all self-esteem
      domains compared to controls. Both ADHD drug-free (47.1%) and ADHD drug-treated
      (44.1%) groups showed significantly higher rates of subjects in the pathological
      range as compared to normal control group (8.8%) (p <.001) with a higher
      percentage of subjects in the pathological range. Among ADHD drug-treated
      subjects, the methylphenidate group showed higher self-esteem scores as compared
      to the atomoxetine group. CONCLUSION: A lower self-esteem profile is more common
      in subjects suffering from ADHD than in healthy controls, suggesting the
      importance of an early detection of psychological well-being in these children in
      order to reduce the ADHD symptoms long-term impacts.

PMID- 23878615
TI  - Social change and increasing of bipolar disorders: an evolutionary model.
AB  - INTRODUCTION: The objective of this paper is to see if behaviours defined as
      pathological and maladjusted in certain contexts may produce adaptive effects in
      other contexts, especially if they occur in attenuated form. Interactions between
      environment and behaviour are studied from an evolutionary standpoint in an
      attempt to understand how new attitudes emerge in an evolving context.
      METHODOLOGY: Narrative review. Following an historical examination of how the
      description of depression in Western society has changed, we examine a series of
      studies performed in areas where great changes have taken place as well as
      research on emigration from Sardinia in the 1960s and 70s and immigration to
      Sardinia in the 1990s. RESULTS AND CONCLUSIONS: If we postulate that mood
      disorders are on the increase and that the epidemic began in the 17th century
      with the "English malady", we must suppose that at least the "light" forms have
      an adaptive advantage, otherwise the expansion of the disorder would have been
      self-limiting. "Compulsive hyper-responsabilization", as well as explorative
      behaviours, may represent a base for adaptation in certain conditions of social
      change. The social emphasis in individualism and responsibility may have changed
      not only the frequency, but also the phenomenology of mood disorders particularly
      the increases in bipolar disorders. From the sociobiological standpoint the
      conditions that may favour "subthreshold" bipolar or depressive features are to
      be considered in relation to the contextual role of gender and the different
      risks of the two disorders in males and females.

PMID- 23878617
TI  - Statistical texture modeling for medical volume using linear tensor coding.
AB  - We introduced a compact representation method named Linear Tensor Coding (LTC)
      for medical volume. With LTC, medical volumes can be represented by a linear
      combination of bases which are mutually independent. Furthermore, it is possible
      to choose the distinctive basis for classification. Before classification,
      correlations between category labels and the coefficients of LTC basis are used
      to choose the basis. Then we use the selected basis for classification. The
      classification accuracy can be significantly improved by the use of selected
      distinctive basis. 

PMID- 23878616
TI  - Application of design of experiment for floating drug delivery of tapentadol
      hydrochloride.
AB  - The aim of the present study was to apply design of experiment (DOE) to optimize
      floating drug delivery of tapentadol hydrochloride. Tapentadol hydrochloride is a
      synthetic opioid used as a centrally acting analgesic and effective in both
      experimental and clinical pain. The half-life of the drug is about 4 hours and
      oral dose is 50 to 250 mg twice a day. For optimization 3(2) full factorial
      design was employed for formulation of tapentadol hydrochloride tablets. Sodium
      bicarbonate was incorporated as a gas-generating agent. Combination of polymers
      Xanthan gum and Locust bean gum was used to achieve controlled release effect.
      The concentration of polymers was considered as the independent variables and
      dependent variables were floating lag time and swelling index of the tablets.
      From the factorial batches, it was observed that formulation containing
      combination of 20% sodium bicarbonate and 10% citric acid shows optimum floating
      ability whereas the formulation containing 20% Xanthan gum and 28% Locust bean
      gum shows optimum sustained drug release pattern with adequate floating. 

PMID- 23878619
TI  - Diltiazem: a reversible cause of atrioventricular block - until proven otherwise.

PMID- 23878618
TI  - Whole apple extracts increase lifespan, healthspan and resistance to stress in
      Caenorhabditis elegans.
AB  - Regular consumption of fruits and vegetables is associated with reduced risk of
      age-related functional decline and chronic diseases such as cancer and
      cardiovascular disease. These effects are primarily attributed to phytochemicals,
      plant compounds with a wide range of biological activities and health benefits.
      Apples, the top contributor of fruit phenolics in American diets, have high
      antioxidant, antiproliferative and chemopreventive activity in vitro and in vivo.
      However, little is known about their effects on aging. The objectives of this
      study were to determine the effects of whole apple phytochemical extracts on
      lifespan, healthspan and resistance to various stresses in vivo using C. elegans
      as a model. The mean and maximum lifespan of animals treated with 2.5, 5 and 10
      mg/ml whole apple extracts increased significantly in a dose-dependent manner by
      up to 39 and 25%, respectively. Healthspan also significantly improved as
      indicated by improved motility and reduced lipofuscin accumulation. Animals pre
      treated with whole apple extracts were more resistant to stresses such as heat,
      UV radiation, paraquat-induced oxidative stress, and pathogenic infection,
      suggesting that cellular defense and immune system functions also improved. Our
      findings indicate that, in C. elegans, whole apple extracts slow aging, extend
      lifespan, improve healthspan, and enhance resistance to stress.

PMID- 23878620
TI  - Risk assessment in mental health: introducing a traffic light system in a
      community mental health team.
AB  - AIMS: To reports a study in which action research approach was utilised to
      introduce a new system of risk assessment, based on traffic lights, into a
      community mental health team. BACKGROUND: Risk management is a serious concern in
      community mental healthcare where there is less direct, real-time supervision of
      clients than in other settings, and because inadequate management of risk can
      have fatal consequences when service users are a risk to themselves and/or
      others. DESIGN: An action research design was undertaken, using three phases of
      Look, Think and Act. METHODS: Data were collected between January and March of
      2012. In the action research phases, qualitative data were collected in focus
      groups with the team's multi-disciplinary mental health professionals. Data were
      transcribed verbatim and analysed thematically, which involved agreement of
      themes and interpretations by two researchers. The Look, Think and Act phases
      guided the development of the project; team members worked collaboratively on the
      traffic light system, implemented and evaluated it. FINDINGS: Themes were
      constructed that were discussed across the focus groups. These themes were: Ease
      of use; Risk identification and management; Legal status; Different teams' views
      of risk; Post-implementation evaluation. CONCLUSION: Action research has been
      used to implement change in mental health risk management. Others internationally
      would benefit from considering a Traffic Light System, and in using action
      research to implement it.

PMID- 23878622
TI  - Timescales of Coherent Dynamics in the Light Harvesting Complex 2 (LH2) of
      Rhodobacter sphaeroides.
AB  - The initial dynamics of energy transfer in the light harvesting complex 2 from
      Rhodobacter sphaeroides were investigated with polarization controlled two
      dimensional spectroscopy. This method allows only the coherent electronic motions
      to be observed revealing the timescale of dephasing among the excited states. We
      observe persistent coherence among all states and assign ensemble dephasing rates
      for the various coherences. A simple model is utilized to connect the
      spectroscopic transitions to the molecular structure, allowing us to distinguish
      coherences between the two rings of chromophores and coherences within the rings.
      We also compare dephasing rates between excited states to dephasing rates between
      the ground and excited states, revealing that the coherences between excited
      states dephase on a slower timescale than coherences between the ground and
      excited states.

PMID- 23878623
TI  - Does the upgrading of the radio communications network in health facilities
      reduce the delay in the referral of obstetric emergencies in Southern Malawi?
AB  - SETTING: Mwanza, Phalombe and Zomba districts in the Southern Region of Malawi.
      BACKGROUND: Radios have been installed in many health centers in the Southern
      Region of Malawi but communication is often indirect. Messages get re-channeled
      from one health center to another before reaching district hospitals. In an
      attempt to strengthen the obstetric referral system, the Safe Motherhood Project
      installed a repeater-based VHF radio communication system in three pilot
      districts. The overall goal of the new network was to enable the health centers
      to communicate directly to their district health offices (DHOs) for an ambulance
      when they have an emergency obstetric complication for referral to the hospital.
      AIM: This study aimed to determine whether or not improving the radio
      communications system reduces the delay in referral of obstetric emergencies from
      health center to hospital. MATERIALS AND METHODS: Data collection was conducted
      between 2001 and 2003 using a range of data collection methods. Radio
      communications register books were placed at each participating health center to
      record information on all women with emergency obstetric complications referred
      to the hospital for further management. An obstetric referral form was completed
      on each woman referred to the hospital. And using the same referral form, the
      referral hospital was required to give feedback to the health centers on
      discharge of the patient. Existing maternity registers or HMIS registers were
      reviewed to obtain additional information not captured in radio communication
      registers. Interviews with health center staff were conducted to obtain their
      communication experiences before and after the new network was installed.
      RESULTS: The average number of obstetric admissions per month and the proportion
      of referrals in the participating health centers significantly increased during
      the post-intervention period. Significantly more emergency obstetric referrals
      were collected under 1 hour between decision to refer by the midwife at the
      health center and arrival of transport from the DHO or base station in the post
      intervention period than pre-intervention period (p<0.02). However, some patients
      still waited for more than 13 hours for transportation in the post-intervention
      period. The median time interval between decision to refer and arrival of
      transport was 3 h. versus 2 h. 3 min. in the pre- and post-intervention periods
      respectively. CONCLUSION: This study has demonstrated that the new VHF radio
      network system has, without doubt, improved the radio communication system in the
      three pilot districts. However, although the time interval between the decision
      to refer and arrival of transport significantly improved after the intervention,
      the majority of transportation still took too long, particularly for someone with
      postpartum hemorrhage. It is very important to improve the management/control of
      obstetric ambulances at district level so as to complement efforts of an improved
      radio communication system in reducing delays in the referral of obstetric
      emergencies.

PMID- 23878621
TI  - The role of the Keap1/Nrf2 pathway in the cellular response to methylmercury.
AB  - Methylmercury (MeHg) is an environmental electrophile that covalently modifies
      cellular proteins with reactive thiols, resulting in the formation of protein
      adducts. While such protein modifications, referred to as S-mercuration, are
      thought to be associated with the enzyme dysfunction and cellular damage caused
      by MeHg exposure, the current consensus is that (1) there is a cellular response
      to MeHg through the activation of NF-E2-related factor 2 (Nrf2) coupled to S
      mercuration of its negative regulator, Kelch-like ECH-associated protein 1
      (Keap1), and (2) the Keap1/Nrf2 pathway protects against MeHg toxicity. In this
      review, we introduce our findings and discuss the observations of other workers
      concerning the S-mercuration of cellular proteins by MeHg and the importance of
      the Keap1/Nrf2 pathway in protection against MeHg toxicity in cultured cells and
      mice. 

PMID- 23878624
TI  - The obstinate maternal mortality ratio for Malawi: an Insult beyond the
      obstetrician! 'A Cri de Coeur'.

PMID- 23878626
TI  - Health related baseline millennium development goals indicators for local
      authorities in Malawi.
AB  - The Malawi Social Action Fund (MASAF) is implementing a 12 year programme to
      close service gaps in rural communities. These service gaps are primarily those
      in health, education, household food security, water and sanitation, transport
      and communications. The impact indicators of the Project are selected Millennium
      Development Goal indicators. MASAF conducted a baseline study of the MDG
      indicators for all districts in Malawi. This paper presents available health
      related MDG baseline indicators for all districts in Malawi. Other stakeholders
      implementing health interventions could use these baseline indicators for
      planning purposes. 

PMID- 23878625
TI  - In-vivo parasitological response to sulfadoxine-pyrimethamine in pregnant women
      in southern Malawi.
AB  - BACKGROUND: Malaria in pregnancy is a significant cause of maternal and infant
      morbidity and mortality. Malawi adopted intermittent preventive treatment with
      sulfadoxinepyrimethamine (SP) for the control of malaria in pregnancy in 1993.
      However there is little information on the in-vivo SP efficacy in pregnant women.
      This study was conducted to determine: prevalence of malaria and anaemia at the
      first antenatal visit and rate of parasitological failure to SP in pregnancy.
      METHODS: A cross-sectional followed by a prospective cohort study was conducted
      in women attending antenatal care clinic at Montfort Hospital in Lower Shire
      Valley from June 2004 to February 2005. Women were screened for malaria and
      anaemia at the first antenatal visit. After taking SP under direct observation,
      women with malaria parasitaemia were followed up to day 14 to determine
      parasitological response. RESULTS: Of 961 women screened, 9% had malaria, 77% had
      anaemia (HB<11.0g/dl), 24% had moderate anaemia (HB 7.0-8.9g/dl) and 6% had
      severe anaemia (HB<7.0g/dl). Malaria was significantly more frequent in
      primigravidae, the second trimester and in the post- rainy season (all p <0.05).
      Moderate anaemia (Hb < 9.0g/dl) was significantly more common in adolescents and
      primigravidae (both p <0.05). In the14-day follow up study, loss to follow up was
      13%. Of the 74 women who completed the follow up, 89% cleared malaria parasites
      successfully and 11% had parasitological failure. Parasitological failures were
      all of the R1 type except for one with R2 failure. CONCLUSION: Anaemia prevalence
      was high at first antenatal visit in this population. Rate of parasitological
      failure to SP in pregnancy increased from 5% in 1996 to 11% in 2004.

PMID- 23878627
TI  - Framework for monitoring equity in access and health systems issues in
      antiretroviral therapy Programmes in southern Africa.
AB  - Universal provision of antiretroviral therapy (ART), while feasible, is
      expensive. In light of this limitation, the World Health Organisation (WHO) has
      launched the 3 * 5 initiative, to provide ART to 3 million people by the end of
      the year 2005. In Southern Africa, large-scale provision of ART will likely be
      achieved through fragile public health systems. ART programmes should therefore
      be developed and expanded in ways that will not aggravate inequities or result in
      the inappropriate withdrawal of resources from other health interventions or from
      other parts of the health system. This paper, proposes a framework for monitoring
      equity in access and health systems issues in ART programmes in Southern Africa.
      It proposes that an equity monitoring system should comprise seven thematic
      areas. These thematic areas encompass a national monitoring system which extends
      beyond one agency or single data collection method. Together with monitoring of
      targets in terms of numbers treated, there should also be monitoring of health
      systems impacts and issues in ART expansion, with reporting both nationally and
      to a regional body. 

PMID- 23878628
TI  - Epidemiology and bacterial colonization of burn injuries in Blantyre.
AB  - Forty-nine patients from the Burns Unit at the QECH had swabs taken from various
      sites in order to determine the bacterial profile and antibiotic susceptibilities
      in burn wounds colonized by bacteria. The mean age was 16 years (range 1-70
      years); 27 (55 %) of the study population were female and 22 (45%) were male.
      Twenty-four (49%) patients were epileptic. Open fire (41%) was the most common
      cause of burn injuries among epileptics while hot water burns (29%) were
      commonest among non-epileptics. Burn injury and percentage total burn surface
      area (% TBSA) injuries decreased with age, and the upper and lower limbs, trunk,
      head and neck were the most commonly affected sites. Staphylococcus aureus was
      the commonest isolate (23%), followed by Proteus mirabilis (22.7%), Streptococci
      spp (15.9%), Pseudomonas aeruginosa (4.5%) and 3.4% for Escherichia coli,
      Salmonella and Klebsiella spp. There was a significant trend of bacterial growth
      with increasing % TBSA (p<0.001). Bacterial growth was significantly more common
      in more recent burns of less than 20 days compared to burns of longer duration
      (OR 4.1 [95% CI 1.58-10.99]). Broad-spectrum antibiotics are required as first
      line therapy for burns-related sepsis but there is need for surveillance of
      antibiotic susceptibility to help determine appropriate therapy. 

PMID- 23878629
TI  - Surgical facilities available at district hospitals in Malawi.

PMID- 23878630
TI  - A review of the role of modifying factors in health education programmes.

PMID- 23878631
TI  - Maternal and newborn health in Malawi.

PMID- 23878632
TI  - A case of late recurrence of Burkitt's Lymphoma presenting with abdominal masses
      and haematemesis.

PMID- 23878633
TI  - Averting maternal deaths.

PMID- 23878635
TI  - A tribute to Dr. Steve Graham.

PMID- 23878634
TI  - Is sulphadoxine-pyrimethamine (SP) still useful as the first-line antimalarial
      drug in Malawi or it must be quickly withdrawn from the antimalarial repertoire?

PMID- 23878636
TI  - The making of a doctor.

PMID- 23878637
TI  - 1. A Qualitative Study of Medical Student Socialization in Malawi's College of
      Medicine: Preclinical Training and Identity.

PMID- 23878638
TI  - 2. A Qualitative Study of Medical Student Socialization in Malawi's College of
      Medicine: Clinical Crisis and Beyond.

PMID- 23878639
TI  - Cigarette smoking among school-going adolescents in Kafue, Zambia.
AB  - INTRODUCTION: Cigarette smoking is a leading cause of global morbidity and
      mortality. Interest in developing countries smoking prevalence has been growing
      since 1999. OBJECTIVES: To estimate the prevalence of current cigarette smoking
      and associated factors among school-age adolescents in Kafue, Zambia. METHODS: A
      cross sectional study was conducted using standard Global Youth Tobacco Survey
      (GYTS) methodology. Frequencies and odds ratios were obtained to assess the
      association between selected factors and current cigarette smoking. RESULTS: Data
      on current smoking were available for 1872 adolescents, of whom 891 (47.6%) were
      males and 981 females. Overall 154 (8.2%) adolescents were current cigarette
      smokers, while 93 (10.4%) males and 61 (6.2%) females were current smokers (p
      <0.001). The majority of the smokers usually smoked at their own home or at a
      friend's house. Having some pocket money, having friends or parents who are
      smokers, and being exposed to pro-tobacco advertisements at social gatherings
      were associated with being a current cigarette smoker. CONCLUSIONS: The
      traditional factors associated with smoking among adolescents elsewhere are also
      associated with smoking among adolescents in Kafue, Zambia. Public health
      interventions aimed to reduce adolescent smoking should be designed with these
      identified associations in mind.

PMID- 23878640
TI  - Determinants of vaccination coverage in Malawi: evidence from the demographic and
      health surveys.
AB  - The purpose of this paper is to identify groups of children in Malawi who are
      less or not reached by vaccination services by using data from the Demographic
      and Health Surveys conducted in Malawi in 1992, 1996, 2000 and 2004. These
      surveys have shown that the proportion of children aged 12-23 months who were
      fully vaccinated by 12 months of age has been decreasing: it was 67% in 1992,
      then 55%, 54% and 51% in 1996, 2000 and 2004, respectively. The review has also
      shown that birth order of the child, residence (rural/urban) and mother's
      education are major determinants of the immunization status of the child. 

PMID- 23878641
TI  - Guidance for National Tuberculosis Programmes on the management of tuberculosis
      in children - an update.
AB  - About one million children develop tuberculosis (TB) annually worldwide.
      Childhood TB is common in Malawi accounting for about 12% of all TB cases.
      Childhood TB differs from TB in adults in ways that have important implications
      for the prevention, diagnosis and treatment of TB in children. Young children
      living in close contact with a case of smear-positive pulmonary TB are at
      particular risk of infection and TB disease. Screening of the household contacts
      of an infectious source case is therefore recommended to identify children with
      TB and enable their prompt treatment, and to provide children who do not have TB
      with isoniazid preventive treatment. It is recognised that there is a need to
      improve the diagnosis and management of children with TB, the prevention of TB in
      children and to ensure their inclusion under the implementation of the Stop TB
      strategy by National TB Programmes. A subgroup of the WHO DOTS Expansion Working
      Group called the Stop TB Partnership Childhood TB Subgroup published guidelines
      for the management of child TB in 2006. The guidelines are designed to complement
      current national and international guidelines on the implementation of the Stop
      TB Strategy and existing guidelines, but also to fill existing gaps to ensure
      that children with M. tuberculosis infection and TB disease are identified early
      and managed effectively. This paper summarises some of the most important
      information and recommendations put forward in those guidelines. 

PMID- 23878642
TI  - Ward round: A patient with blurred vision and leg weakness.

PMID- 23878643
TI  - Ward round: Chronic respiratory symptoms with no response to tuberculosis
      treatment in a 35 year old HIV positive man.

PMID- 23878644
TI  - The role of medical and social history in addressing relative contraindications
      to antiretroviral medications.

PMID- 23878646
TI  - The Village Man who became a Doctor.

PMID- 23878645
TI  - Human bite and HIV transmission.

PMID- 23878647
TI  - Anthem of appreciation.

PMID- 23878648
TI  - 2nd Annual HIV and AIDS and Nutrition Research Dissemination Conference:
      Abstracts from symposiom held at College of Medicine in January 2007.

PMID- 23878649
TI  - Editorial - the role of carers.

PMID- 23878650
TI  - Providing An audit of how patients get on to antiretroviral therapy in Malawi,
      and the weight gain they experience in the first six months.
AB  - An operational study was conducted in 6 public sector health facilities in the
      Southern Region of Malawi to determine a) drop-out rates during the referral
      process of patients to antiretroviral therapy (ART) and b) weight gained during
      the first 6 months in patients who were alive and on ART at that time. There were
      738 adult HIV-infected eligible patients booked for group counseling, of whom 550
      (74.5%) attended individual counseling and started ART. 16% of patients dropped
      out between booking and group counseling and 9.5% between group counseling and
      start of ART. In patients who were alive and on ART 6 months after starting,
      there was a gradual increase in weight with a mean gain of 6.0 kg in men and 5.0
      kg in women. There was a slight increase in weight gain in patients in WHO
      Clinical Stage 3 and 4 compared with those in Stage 1&2, although this was only
      significant at 6-months between women in Stage 4 compared with women in Stage 1&2
      (p <0.05). More information is needed on why patients drop out of the counseling
      process before starting ART, and whether weight gain is a marker for survival in
      the early months of ART. 

PMID- 23878651
TI  - Prevalence of HIV, HepBsAg and Hep C antibodies among inmates in Chichiri prison,
      Blantyre, Malawi.
AB  - OBJECTIVE: To determine HIV, HepatitisBsAg and Hepatitis C antibodies including
      knowledge, attitudes, practices and risk factors that may facilitate the spread
      of HIV among inmates at Chichiri Prison, Blantyre, Malawi. DESIGN: This was a
      cross sectional study. Informed consent was sought from each of the participants
      before interviewer-administered questionnaires were used to collect socio
      demographic data. Blood specimens were collected for HIV and hepatitis B and C
      serology. SETTING: Chichiri Prison in Blantyre which is one of the largest prison
      facilities in Malawi. Adult males and female inmates participated while juveniles
      were excluded. RESULTS: A total of 164 prison inmates comprising 142 males
      (86.6%) and 22 females (13.4%) participated in the study. The age range was 18-65
      years with mean age at 28.6 years. Overall HIV prevalence rate was 36.6%; among
      male inmates it was 29.9%, and among the 22 female inmates tested, 11(50%) were
      reactive. Five males (3.5%) tested positive for HepBsAg with one of them dually
      infected with HIV. All participants were hepatitis C negative. 141 (86%) inmates
      acknowledged that they knew that man to man sex occured in the prison, 55(33.5%)
      believed that mosquito bites could spread HIV; 33(20.1%) said that sex was the
      only way HIV could be spread, 8(4.9%) thought that HIV/AIDS could be spread
      through food sharing. 20 (12.2%) believed that HIV couldn't be spread from mother
      to child and 135 (82.3%) acknowledged that tattooing was practiced among the
      inmates. 130(79.3%) acknowledged knowledge of use of cannabis in prison; 3 (2.1%)
      male inmates actually accepted being homosexuals. None of the inmates reported
      knowledge of use of injectable drugs within the prison. CONCLUSIONS: HIV
      prevalence rate (36.6 %) at the Chichiri Prison is higher than the national
      average of 14%, while female infection rates were higher than males. There are
      gaps in the inmates' knowledge of the epidemiology of HIV which need to be
      bridged through awareness programmes. Homosexuality and injecting drug use may
      not be a major factor in HIV transmission within prisons in Malawi. The low
      prevalence of Hepatitis BsAg (3.5%) and the inability to detect Hepatitis C
      antibodies deserve further study.

PMID- 23878653
TI  - The worth of malawian women: a review of the current status of safe motherhood in
      Malawi.

PMID- 23878652
TI  - Providing insecticide treated bed nets in antiretroviral treatment clinics in
      Malawi: a pilot study.
AB  - HIV infection and malaria, two of the most common and important health problems
      in sub-Saharan Africa, have been demonstrated to have interactive pathology. In
      Malawi, where malaria is endemic, and antiretroviral therapy (ART) delivery is
      scaling up, we piloted integration of long-lasting insecticide-treated bednets
      (ITN) provision in three ART clinics. In July 2006, 1,910 ITNs were delivered to
      pilot sites, and ART clinic staff personnel were briefed on ITN provision and use
      of a monitoring system. Sites were assessed using a structured questionnaire in
      December 2006. During the pilot period, 1,282 ITNs were distributed to patients.
      A large proportion (70%) of ART patients at these sites received pilot study
      ITNs. Site adherence to the monitoring system was variable. Seventeen patients
      were interviewed, 14 of whom were ART patients who had received ITNs; 11 of these
      (79%) had slept under the net the previous night. This pilot demonstrates the
      feasibility of ITN distribution to patients attending ART clinics in Malawi.
      Programmatic and policy considerations for national roll-out include the need to:
      1) adopt a standardized monitoring system, 2) develop information, education, and
      communication materials, 3) develop in-service training for ART clinicians, and
      4) identify systems for forecasting, procuring and distributing ITNs. 

PMID- 23878654
TI  - Advocating for the Improvement of Adolescent VCT Services in Malawi.

PMID- 23878655
TI  - A case series of brain abscesses in Malawian children.
AB  - We report three cases of brain abscess in children admitted to QECH in 2006. All
      children were HIV-uninfected. One case was associated with staphylococcal
      empyema, another with chronic suppurative otitis media and mastoiditis, and the
      third case had no identified extracranial focus of infection. These cases
      illustrate the difficulties of diagnosis and management of brain abscesses in the
      resource-poor setting where other causes of infection of the central nervous
      system are common. The typical clinical presentation of brain abscess of altered
      mental state and seizures is also characteristic of cerebral malaria and
      meningitis and it is likely that many cases of brain abscess in Malawian children
      are not diagnosed. The value of cranial CT scan, ideally with contrast, for
      diagnosis and management of brain abscess is highlighted by these cases. 

PMID- 23878656
TI  - Ward Round: a jaundiced 43 year old man with cavitary lessions on chest
      radiograph.

PMID- 23878657
TI  - What is the role of a Grandmother in a Malawian society and how can we as health
      care workers support her?

PMID- 23878658
TI  - Retiring gracefully.

PMID- 23878659
TI  - AIDS and food insecurity: 'new variant famine' in Malawi?

PMID- 23878660
TI  - Who is accessing antiretroviral therapy in Malawi? A study in the Southern Region
      on the occupation category "other".
AB  - As part of quarterly national reports on the scale up of antiretroviral therapy
      (ART), demographic and clinical characteristics are recorded including data on
      occupation. The largest occupational category is that of "other". As there is no
      information on the composition of the different occupations of patients placed in
      this category, a formal study was therefore conducted in 6 representative public
      sector facilities in the Southeastern Region of Malawi. Between January to June
      2006, there were 126 adult patients recorded as "other" in the occupation column.
      A great variety of different occupations was recorded including no employment
      30%, administration jobs 24%, general labourers 11%, builders 10%, tailors 9% and
      drivers 7%. A wide range of people with different jobs are accessing ART, and
      this should help in improving the economy of the patients as well as the country
      at large. 

PMID- 23878661
TI  - Presentation of trypanosomiasis in nkhotakota.
AB  - In 2002, we identified 28 people in Nkhotakota District who were suffering from
      Human African Trypanosomiasis (HAT). Sixteen of these were identified when they
      presented to the District Hospital with a febrile illness. The remaining twelve
      were identified through a rural cross-sectional survey, in which 500 people were
      visited in their homes, persons found to be febrile, were examined by blood film
      microscopy. Of the 28 people, 50% (14) presented within a month of the onset of
      symptoms. Sixteen (57%) had splenomegaly, and 24 were anaemic ([Hb] <12 g/dl).
      Four patients died (14%), of which two were in the late stage of the disease.
      None of the patients recall having a chancre that could be attributed to the bite
      of tsetse flies. 9 out of 28 (32%) reported illness longer than 90 days. Of the 9
      patients 6 (66%) of them remained in the early stage after reporting illness of
      180 days. This study reports on the prevalence and clinical features of
      Trypansoma brucei rhodesiense infection in a endemic district in Malawi. 

PMID- 23878663
TI  - Maternal anthropometry and weight gain as risk factors for poor pregnancy
      outcomes in a rural area of southern Malawi.

PMID- 23878662
TI  - Challenges of Childhood TB/HIV Management in Malawi.
AB  - The diagnosis and management of childhood tuberculosis (TB) are major challenges
      in countries such as Malawi with high incidence of TB and human immunodeficiency
      virus (HIV) infection. Diagnosis of TB in children often relies only on clinical
      features but clinical overlap with the presentation of HIV and other HIV-related
      lung disease is common. The tuberculin skin test (TST), the standard marker of M.
      tuberculosis infection in immune competent children, has poor sensitivity in HIV
      infected children and is not usually available in Malawi. HIV test should be
      routine in children with suspected TB as it improves clinical management. HIV
      infected children are at increased risk of developing active disease following TB
      exposure which justifies the use of isoniazid preventive therapy (IPT) once
      active disease has been excluded but this is difficult to implement and
      appropriate duration of IPT is unknown. HIV-infected children with active TB
      experience higher mortality and relapse rates on standard TB treatment compared
      to HIV-uninfected children, highlighting the need for further research to define
      optimal treatment regimens. HIV-infected children should also receive appropriate
      supportive care including cotrimoxazole prophylaxis and anti-retroviral treatment
      (ART) if indicated. There are concerns about concurrent use of some anti-TB drugs
      such as rifampicin with some ARTs. 

PMID- 23878664
TI  - Trends in life expectancy and the macroeconomy in Malawi.
AB  - This paper studies the trends in life expectancy in Malawi since independence and
      offers possible explanations regarding inter-temporal variations. Descriptive
      analysis reveals that the life expectancy in Malawi has trailed below the Sub
      Saharan African average. From the 1960s through to the early 1980s life
      expectancy improved driven mainly by rising incomes and the absence of HIV/AIDS.
      In the mid 1980s life expectancy declined tremendously and never improved due to
      the spread of HIV/AIDS, the economic slump that followed the World Bank's
      Structural Adjustment programmes (SAP) and widespread corruption and poor
      governance in the era of democracy. At the turn of the new millennium, Malawians
      were no healthier than their ancestors at the dawn of independence though this
      improved after 2004. If Malawi is to meet its health Millennium Development Goals
      by 2015, good governance, improved agricultural performance and an increase in
      health expenditure should be at the heart of its development policies. 

PMID- 23878665
TI  - Always wanting to change things for the better.

PMID- 23878666
TI  - Malawi health news.

PMID- 23878667
TI  - Report on the workshop "Enhancing Clinical Trial Oversight in Malawi".

PMID- 23878668
TI  - Report on medical association of Malawi annual general meeting - april 2008.

PMID- 23878681
TI  - Microbiological hazard analysis of ready-to-eat meats processed at a food plant
      in Trinidad, West Indies.
AB  - BACKGROUND: A bacteriological assessment of the environment and food products at
      different stages of processing was conducted during the manufacture of ready-to
      eat (RTE) chicken franks, chicken bologna and bacon at a large meat processing
      plant in Trinidad, West Indies. METHODS: Samples of air, surfaces (swabs), raw
      materials, and in-process and finished food products were collected during two
      separate visits for each product type and subjected to qualitative or
      quantitative analysis for bacterial zoonotic pathogens and fecal indicator
      organisms. RESULTS: Staphylococcus aureus was the most common pathogen detected
      in pre-cooked products (mean counts = 0.66, 1.98, and 1.95 log10CFU/g for franks,
      bologna, and bacon, respectively). This pathogen was also found in unacceptable
      levels in 4 (16.7%) of 24 post-cooked samples. Fifty percent (10 of 20) of pre
      cooked mixtures of bacon and bologna were contaminated with Listeria spp.,
      including four with L. monocytogenes. Pre-cooked mixtures of franks and bologna
      also contained E. coli (35 and 0.72 log10 CFU/g, respectively) while 5 (12.5%) of
      40 pre-cooked mixtures of chicken franks had Salmonella spp. Aerobic bacteria
      exceeded acceptable international standards in 46 (82.1%) of 56 pre-cooked and 6
      (16.7%) of 36 post-cooked samples. Both pre-and post-cooking air and surfaces had
      relatively high levels of aerobic bacteria, Staphylococcus aureus and coliforms,
      including equipment and gloves of employees. A drastic decrease in aerobic counts
      and Staphylococcus aureus levels following heat treatment and subsequent increase
      in counts of these bacteria are suggestive of post-cooking contamination.
      CONCLUSION: A relatively high level of risk exists for microbial contamination of
      RTE meats at the food plant investigated and there is a need for enhancing the
      quality assurance programs to ensure the safety of consumers of products
      manufactured at this plant.

PMID- 23878682
TI  - Divorcing diagnosis from treatment: contemporary management of low-risk prostate
      cancer.
AB  - Today, the majority of men with newly diagnosed prostate cancer will present with
      low-risk features of the disease. Because prostate cancer often takes an
      insidious course, it is debated whether the majority of these men require radical
      treatment and the accompanying derangement of quality of life domains imposed by
      surgery, radiation, and hormonal therapy. Investigators have identified various
      selection criteria for "insignificant disease," or that which can be monitored
      for disease progression while safely delaying radical treatment. In addition to
      the ideal definition of low risk, a lack of randomized trials comparing the
      various options for treatment in this group of men poses a great challenge for
      urologists. Early outcomes from active surveillance cohorts support its use in
      carefully selected men with low-risk disease features, but frequent monitoring is
      required. Patient selection and disease monitoring methods will require
      refinement that will likely be accomplished through the increased use of
      biomarkers and specialized imaging techniques. 

PMID- 23878683
TI  - Endoscopic management of upper urinary tract urothelial carcinoma.
AB  - Upper urinary tract urothelial carcinoma (UTUC) is relatively uncommon. Radical
      nephroureterectomy with an ipsilateral bladder cuff excision has been the gold
      standard treatment for UTUC. However, recent advances in technology have made
      possible the increased use of endoscopic management for the treatment of UTUC.
      The definitive goal of endoscopic management of UTUC is cancer control while
      maintaining renal function and the integrity of the urinary tract. Endoscopic
      management includes both the retrograde ureteroscopic and antegrade percutaneous
      approaches. The endoscopic management of UTUC is a reasonable alternative for
      patients with renal insufficiency or a solitary functional kidney, bilateral
      disease, or a significant comorbidity that precludes radical surgery. Select
      patients with a functional contralateral kidney who have low-grade, low-stage
      tumors may also be candidates for endoscopic management. The careful selection of
      patients is the most important point for the successful endoscopic management of
      UTUC. It is crucial that patients are compliant and motivated, because a lifetime
      protocol of strict surveillance is necessary. Adjuvant topical therapy with
      Bacillus Calmette-Guerin or mitomycin C can be used after endoscopic management
      of UTUC in an attempt to reduce recurrence. In this article, we review current
      endoscopic techniques, indications for endoscopic treatment, clinical outcomes of
      endoscopic management, adjuvant topical therapy, and surveillance in patients
      with UTUC. 

PMID- 23878684
TI  - External validation of the cancer of the prostate risk assessment-s score in
      koreans undergoing radical prostatectomy.
AB  - PURPOSE: To evaluate the validity of the University of California San Francisco
      Cancer of the Prostate Risk Assessment-S score (CAPRA-S score), a biochemical
      indicator of recurrent prostate cancer that uses histopathologic data, in Korean
      prostate cancer patients. MATERIALS AND METHODS: A total of 203 prostate cancer
      patients who underwent radical prostatectomy between February 1997 and November
      2010 were observed for longer than 6 months. The CAPRA-S score of 134 patients
      for whom records were available for preoperative prostate-specific antigen (PSA),
      pathologic specimen Gleason score, surgical margin, seminal vesicle invasion,
      extracapsular extension, and lymph node invasion were calculated. Biochemical
      recurrence was defined as repetitive measurement of PSA >=0.2 ng/mL at least 6
      months after surgery with at least a 4-week interval. The Cox proportional hazard
      model and Kaplan-Meier analysis were used for the statistical testing. RESULTS:
      The CAPRA-S scores were divided into nine groups. The 5-year disease-free
      survival rate was reduced as the CAPRA-S score increased compared with the group
      with a CAPRA-S score of 0-1. The CAPRA-S score in this study was more sensitive
      to biochemical recurrence than was the CAPRA score conducted at this institution
      (CAPRA-S concordance index, 0.776; CAPRA concordance index, 0.728). CONCLUSIONS:
      The CAPRA-S score is judged to be a useful tool for predicting the disease-free
      survival rate of Korean prostate cancer patients and is thought to assist in
      establishing postoperative management.

PMID- 23878685
TI  - Efficacy of using three-tesla magnetic resonance imaging diagnosis of capsule
      invasion for decision-making about neurovascular bundle preservation in robotic
      assisted radical prostatectomy.
AB  - PURPOSE: To evaluate the efficacy of using 3-tesla (T) magnetic resonance imaging
      (MRI) diagnosis of extracapsular extension (ECE) for decision-making about
      neurovascular bundle (NVB) preservation in robot-assisted radical prostatectomy
      (RARP) for prostate cancer (PC). MATERIALS AND METHODS: We prospectively
      collected data on PC patients (n=67) who underwent preoperative 3-T MRI before
      RARP. The choice between nerve sparing or resection was based on 3-T MRI findings
      of ECE. We compared the MRI findings with the pathological data on surgical
      margins. Our clinical staging in this study was defined only by MRI. RESULTS:
      When the data were divided by prostate lobe (right lobe or left lobe, n=134), 3-T
      MRI showed 28 positive cases of ECE in 134 prostate lobes, allowing NVB
      preservation in 42 cases (31.3%). Nerve-sparing surgery was achieved in 38.7% of
      cases in which clinical T2 staging by MRI was reported. The pathological data
      revealed that 10 of 134 prostate lobes had positive ECE. The overall sensitivity,
      specificity, positive predictive value, and negative predictive value for
      predicting stage T3 (positive ECE) by side were 60.0% (12 of 20 sides), 86.0% (98
      of 114 sides), 42.9% (12 of 28 sides), and 92.5% (98 of 106 sides), respectively.
      CONCLUSIONS: Three-T MRI prior to RARP enables the use of ECE diagnosis to guide
      decision-making about NVB preservation, with comparatively high specificity and
      negative predictive value. Further prospective studies are underway to reach more
      definitive conclusions.

PMID- 23878686
TI  - Surgical Outcome of Excision and End-to-End Anastomosis for Bulbar Urethral
      Stricture.
AB  - PURPOSE: Although direct-vision internal urethrotomy can be performed for the
      management of short, bulbar urethral strictures, excision and end-to-end
      anastomosis remains the best procedure to guarantee a high success rate. We
      performed a retrospective evaluation of patients who underwent bulbar end-to-end
      anastomosis to assess the factors affecting surgical outcome. MATERIALS AND
      METHODS: We reviewed 33 patients with an average age of 55 years who underwent
      bulbar end-to-end anastomosis. Stricture etiology was blunt perineal trauma
      (54.6%), iatrogenic (24.2%), idiopathic (12.1%), and infection (9.1%). A total of
      21 patients (63.6%) underwent urethrotomy, dilation, or multiple treatments
      before referral to our center. Clinical outcome was considered a treatment
      failure when any postoperative instrumentation was needed. RESULTS: Mean
      operation time was 151 minutes (range, 100 to 215 minutes) and mean excised
      stricture length was 1.5 cm (range, 0.8 to 2.3 cm). At a mean follow-up of 42.6
      months (range, 8 to 96 months), 29 patients (87.9%) were symptom-free and
      required no further procedure. Strictures recurred in 4 patients (12.1%) within 5
      months after surgery. Of four recurrences, one patient was managed successfully
      by urethrotomy, whereas the remaining three did not respond to urethrotomy or
      dilation and required additional urethroplasty. The recurrence rate was
      significantly higher in the patients with nontraumatic causes (iatrogenic in
      three, infection in one patient) than in the patients with traumatic etiology.
      CONCLUSIONS: Excision and end-to-end anastomosis for short, bulbar urethral
      stricture has an acceptable success rate of 87.9%. However, careful consideration
      is needed to decide on the surgical procedure if the stricture etiology is
      nontraumatic.

PMID- 23878687
TI  - Predictive factors for bleeding during percutaneous nephrolithotomy.
AB  - PURPOSE: Although percutaneous nephrolithotomy (PCNL) has been accepted as a
      standard method for the management of large renal stones, the incidence of renal
      hemorrhage is relatively high. This study investigated the variables that affect
      bleeding during PCNL. MATERIALS AND METHODS: The medical records of 370 patients
      who underwent PCNL by a single surgeon from January 2005 to December 2010 were
      reviewed retrospectively. All patients were divided into two groups according to
      median blood loss (lesser bleeding group and higher bleeding group). Various
      clinical and perioperative factors including age, sex, stone size and position,
      degree of hydronephrosis, operative time, underlying disease, history of
      anticoagulant medication, presence of previous nephrostomy catheter, stone
      composition, and thickness of the renal cortex were assessed. For statistical
      assessment, univariate and multivariate logistic regression analyses were used.
      RESULTS: The mean patient age was 48.8 years (range, 22 to 75 years). Forty-three
      patients (11.6%) received a transfusion and 9 patients (2.4%) underwent
      angioembolization after surgery. The mean blood loss was 511.8+/-341.3 mL. Body
      mass index (BMI), stone size, stone position, operation time, and degree of
      preoperative hydronephrosis were predictive factors for severe bleeding during
      PCNL. CONCLUSIONS: On the basis of the results achieved by a single surgeon,
      staghorn stones, high BMI, large stones, prolonged operation time, and absence of
      hydronephrosis were significantly associated with the risk of severe bleeding
      during PCNL.

PMID- 23878688
TI  - Stone attenuation value and cross-sectional area on computed tomography predict
      the success of shock wave lithotripsy.
AB  - PURPOSE: To identify the parameters on noncontrast computed tomography (NCCT)
      that best predict the success of shock wave lithotripsy (SWL). MATERIALS AND
      METHODS: We reviewed the records of 75 patients who underwent SWL for urinary
      calculi measuring 5 to 20 mm. Using NCCT images, we estimated the largest stone
      cross-sectional area and contoured the inner edge of the stone. Clinical outcome
      was classified as successful (stone-free or <4 mm in diameter) or failed (stone
      fragments, >=4 mm). The impact of preoperative parameters was evaluated by
      univariate and multivariate analysis. RESULTS: The overall success rate was
      73.3%. Average stone attenuation value, stone length, and stone cross-sectional
      area in the success and failure groups were 627.4+/-166.5 HU (Hounsfield unit)
      vs. 788.1+/-233.9 HU (p=0.002), 11.7+/-3.8 mm vs. 14.2+/-3.6 mm (p=0.015), and
      0.31+/-0.17 cm(2) vs. 0.57+/-0.41 cm(2) (p<0.001), respectively. In the
      multivariate analysis, stone attenuation value was the only independent predictor
      of SWL success (p=0.023), although stone cross-sectional area had a tendency to
      be associated with SWL success (p=0.053). Patients were then classified into four
      groups by using cutoff values of 780 HU for stone attenuation value and 0.4 cm(2)
      for cross-sectional area. By use of these cutoff values, the group with a low
      stone attenuation value and a low cross-sectional area was more than 11.6 times
      as likely to have a successful result on SWL as were all other groups (odds
      ratio, 11.6; 95% confidence interval, 3.9 to 54.7; p<0.001). CONCLUSIONS: Stone
      attenuation value and stone cross-sectional area are good predictors of
      extracorporeal SWL outcome.

PMID- 23878689
TI  - Factors affecting the outcome of extracorporeal shock wave lithotripsy for
      unilateral urinary stones in children: a 17-year single-institute experience.
AB  - PURPOSE: Extracorporeal shock wave lithotripsy (ESWL) is a first-line treatment
      for pediatric urinary stone disease. We aimed to determine the factors affecting
      the outcome of ESWL for unilateral urinary stones in children. MATERIALS AND
      METHODS: A total of 81 pediatric patients aged 0 to 16 years with urinary stones
      treated by ESWL from January 1995 through May 2012 were retrospectively reviewed.
      All patients were required to have unilateral urinary stone disease. Children who
      underwent other surgical procedures before ESWL were excluded. Outcomes evaluated
      after ESWL were the stone-free rate at 3 months after ESWL, success within a
      single session, and success within three sessions. Factors affecting the success
      within three sessions were also analyzed. RESULTS: The final analysis was for 42
      boys and 22 girls (mean age, 9.2+/-5.2 years). Of these 64 patients, 58 (90.6%)
      were treated by ESWL without other surgical procedures and 54 (84.4%) were
      successfully treated within three ESWL sessions. In the multivariate analysis,
      multiplicity (odds ratio [OR], 0.080; 95% confidence interval [CI], 0.012 to
      0.534; p=0.009) and large stone size (>10 mm; OR, 0.112; 95% CI, 0.018 to 0.707;
      p=0.020) were significant factors that decreased the success rate within three
      ESWL sessions. CONCLUSIONS: Most of the pediatric urinary stone patients in our
      study (90.6%) were successfully treated by ESWL alone without additional
      procedures. If a child has a large urinary stone (>10 mm) or multiplicity,
      clinicians should consider that several ESWL sessions might be needed for
      successful stone fragmentation.

PMID- 23878690
TI  - How Serious Is Erectile Dysfunction in Men's Lives? Comparative Data From Korean
      Adults.
AB  - PURPOSE: Whereas sexual function has long been assumed to be an important
      component of adult men's lives, the impact of sexual dysfunction has not been
      estimated in parallel to other modern disease entities. We compared the
      seriousness of erectile dysfunction (ED) with that of other diseases by use of
      self-administered questionnaires. MATERIALS AND METHODS: Between January 2012 and
      July 2012, 434 healthy male volunteers (group 1) and 263 ED patients (group 2)
      were enrolled. The questionnaire consisted of the following: "If you must undergo
      only one disease in all your life, which disease could you select among these
      items or ED?" The comparative disease entities included hypertension, diabetes
      mellitus (oral hypoglycemic agent/insulin injection), hemodialysis, myocardial
      infarction, herpes zoster, chronic sinusitis, chronic otitis media, gastric
      cancer (early/late), lung cancer (early/late), liver cancer (early/late), and
      dementia. RESULTS: Group 1 recognized ED as being a more serious disease than
      hypertension, diabetes mellitus (oral hypoglycemic agent), herpes zoster, chronic
      sinusitis, and chronic otitis media. In comparison, group 2 recognized ED as
      being a more serious condition than diabetes mellitus (insulin injection) and
      dementia (p<0.001 and p<0.001, respectively). In particular, ED was deemed to be
      more serious than hemodialysis, gastric cancer (early), lung cancer (early), and
      liver cancer (early) by men in group 2 in their 30s to 40s, and these results
      were statistically significant compared with the same age subgroups in group 1
      (p<0.001, p<0.007, p<0.02, and p<0.007, respectively). CONCLUSIONS: In contrast
      with their healthy counterparts, Korean men with ED recognized ED as being as
      serious as hemodialysis, dementia, and early stage cancer, which reflects the
      severe bother of ED in Korean patients.

PMID- 23878691
TI  - Long-term Treatment Outcomes Between Surgical Correction and Conservative
      Management for Penile Fracture: Retrospective Analysis.
AB  - PURPOSE: Early surgical management is the standard of care for penile fracture.
      Conservative treatment is an option with recent reports revealing lower success
      rates. We reviewed the data and long-term outcomes of patients with penile injury
      submitted to surgical or conservative treatment. MATERIALS AND METHODS: Between
      January 2004 and February 2012, 42 patients with penile blunt trauma on an erect
      penis were admitted to our center. We analyzed the following variables: age,
      etiology, symptoms and signs, diagnostic tests, treatment used, complications and
      erectile function during the follow-up. One patient was excluded due to missing
      information. Thirty-five patients underwent surgical repair and 6 patients were
      submitted to conservative management. RESULTS: Mean follow-up was 19.2 months
      (range, 7 days to 72 months). The mean elapsed time from trauma to surgery was
      21.3+/-12.5 hours. Trauma during sexual relationship was the main cause (80.9%)
      of penile fracture. Urethral injury was present in five patients submitted to
      surgery. Dorsal vein injury occurred in three patients with false penile fracture
      and concomitant spongious corpus lesion was present in three patients. During
      follow-up, 31 cases (88.6%) of the surgical group and four cases (66.7%) of the
      conservative group reported sufficient erections for intercourse, with no voiding
      dysfunction and no penile curvature. However, the remaining two patients (33.3%)
      from the conservative group developed erectile dysfunction and three patients
      (50%) developed penile deviation. CONCLUSIONS: Surgical approach provides
      excellent functional outcomes and lower complications. Early surgical management
      of penile fracture provides superior results and conservative approach should be
      avoided.

PMID- 23878692
TI  - Antimicrobial Resistance Pattern in Enterococcus faecalis Strains Isolated From
      Expressed Prostatic Secretions of Patients With Chronic Bacterial Prostatitis.
AB  - PURPOSE: Enterococcus faecalis is one of the most common pathogens linked to
      chronic bacterial prostatitis (CBP). Owing to a limited number of previous
      studies addressing this topic, we aimed to determine the drug resistance patterns
      of E. faecalis strains isolated from CBP patients. MATERIALS AND METHODS: One
      thousand twenty-one patients visited a single hospital owing to chronic
      prostatitis for 5 years. Culture specimens were obtained by use of a modified
      Meares-Stamey method. The minimal inhibitory concentrations of the antimicrobials
      were assessed by use of the Vitek II microbial identification system as suggested
      by the Clinical and Laboratory Standards Institute. RESULTS: Forty-one samples
      from 41 patients who had significant E. faecalis loads for defining CBP were
      included in this study. The E. faecalis strains in our study were resistant to
      penicillin (9.7%), ampicillin (0%), ampicillin/sulbactam (0%), nitrofurantoin
      (0%), imipenem (0%), vancomycin (0%), teicoplanin (0%), quinupristin/dalfopristin
      (100%), ciprofloxacin (9.7%), levofloxacin (4.8%), norfloxacin (26.8%),
      erythromycin (95%), gentamicin (46.3%), tetracycline (97.5%), and
      trimethoprim/sulfamethoxazole (31.5%), respectively. CONCLUSIONS:
      Fluoroquinolones have been the preferred antibiotics for treating CBP. Because of
      their low rate of drug resistance, fluoroquinolones are suitable therapeutic
      agents for E. faecalis strains causing CBP in Korea. Even though tetracycline,
      erythromycin, and trimethoprim/sulfamethoxazole have been prescribed as an
      empirical antimicrobial therapy for chronic prostatitis, we cannot recommend
      these drugs for treatment of E. faecalis isolates because of the high rates of
      drug resistance.

PMID- 23878693
TI  - Bilateral single ectopic ureters draining into a grossly dilated vagina in an
      adolescent female.
AB  - A 16-year-old female presented with dribbling of urine along with voluntary
      voiding since birth. Renal imaging revealed hydroureteronephrosis on the right
      side; the uterus and ovary were normal. A radionuclide scan showed a left
      nonfunctional kidney. On cystovaginoscopy, the urethra was shown to be normal and
      the urinary bladder was tubular with small capacity and an absent trigone.
      Although the vagina was capacious, no ureteric orifices were found. Computed
      tomography corroborated the diagnosis of bilateral, single ectopic ureters
      draining into a grossly dilated vagina. This case is unique because it is a
      bilateral single-system ureteral ectopia in a completely differentiated female
      genital tract that presented late in adolescence. To the best of our knowledge,
      this is the second such ureteral abnormality reported in the literature so far.
      The patient underwent ileocystoplasty with right ureteric reimplantation and
      nephroureterectomy for the left nonfunctional kidney, which histopathology showed
      to be tuberculosis. The patient is continent with cystometric capacity of more
      than 300 mL. 

PMID- 23878694
TI  - Prostate metastasis of malignant melanoma.
AB  - Metastatic malignant melanoma of the prostate is extremely rare in clinical
      practice, and only one case has been reported in the English literature in the
      past 30 years. We report a case of malignant melanoma that metastasized to the
      prostate and review the current literature. A 50-year-old man with a history of
      malignant melanoma metastasis to the left axilla, which was excised 3 years ago,
      presented with lower urinary tract symptoms and gross hematuria. He underwent
      cystoscopy and transurethral resection of the prostate. The pathological
      examination showed metastatic malignant melanoma of the prostate gland. The
      patient died 6 months after the transurethral resection. 

PMID- 23878695
TI  - Microbial aetiologic agents associated with pneumonia in immunocompromised hosts.
AB  - Pulmonary infections are a major cause of morbidity and mortality in the
      immunosuppressed patients. The aim of this study was to determine the etiologic
      agents and predisposing factors associated with pneumonia infections in
      immunocompromised patients. Cross-sectional survey of 100 immunocompromised
      patients due to HIV and Mycobacterium tuberculosis infections were enlisted for
      the study. The patients completed a structured questionnaire to abstract
      information on demographic features and risk factors. Sputum samples were
      collected from the patients with clinical suspicion of having pneumonia and the
      sputa examined by cultural methods. The tuberculosis patients had the highest
      number of isolates, 119 (70%) while those with co-infections of HIV/AIDS and
      tuberculosis had 41(24.1%) and those with only HIV infection were 10 (5.9%). The
      distribution of isolates were as follows, Staphylococcus aureus 63 (37.9%),
      Streptococcus pyogenes 44 (25.9%), Streptococcus pneumoniae 27 (15.9%), Candida
      albicans 24 (14.1%), Klebsiella pneumoniae 7 (4.1%), Proteus mirabilis 4 (2.4%)
      and Escherichia coli 1 (0.5%). Those with previous history of alcoholism and
      tobacco smoking had relatively high isolates. This study demonstrated that
      secondary infections are prevalent in the immunocompromised patients due to
      HIV/AIDS and TB or co-infection with TB/HIV-AIDS. This may lead to drug
      resistance, DOTS or HAART programme, thereby leading to high mortality and
      morbidity. 

PMID- 23878696
TI  - A Systematic Review of the Epidemiology of Mansonelliasis.

PMID- 23878697
TI  - Artesunate Plus Amodiaquine (AS+AQ) Versus Artemether -Lumefantrine (AL) for the
      Treatment of Uncomplicated Plasmodium Falciparum Malaria in Sub-Saharan Africa-A
      Meta-Analysis.
AB  - The purpose of this study is to summarize the available data on the efficacy of
      Artesunate plus Amodiaquine (AS+AQ) versus Artemether -Lumefantrine (AL) for the
      treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa
      using uncorrected parasitaemia as a clinically relevant endpoint. Studies and
      conference abstracts identified through Pubmed, Medline, Embase, Ansinet, AJOL,
      Bioline, Cochrane Infectious Diseases Group trials register, The Cochrane
      Controlled Trials Register, Science Citation Index, Lilacs, African Index
      Medicus, Clusty, Google, Yahoo and Microsoft search engines. Randomized
      controlled clinical trials comparing Artesunate-Amodiaquine versus Artemether
      Lumefantrine, in Sub-Saharan Africa from January 2004 to June 2009, and which had
      at least 30 patients per study arm. The authors independently applied the
      inclusion criteria, assessed methodological quality and extracted data into a
      predesigned form. The outcome of interest was uncorrected day 28 parasitological
      failure. Data were then checked for agreement and double entered into RevMan
      version 5 for further analyses. Fifteen trials (4265 participants) met the
      inclusion criteria. Day 28 parasitological failure was lower for AL (286 of 2201
      participants or 13.0 % failures) when compared with AS+AQ (446 of 2424
      participants or 18.4% failures). The relative risk of parasitological failure
      with AS+AQ was higher when compared with AL (RR 1.65, 95% CI, 1.18-2.32). There
      were significant heterogeneity and inconsistencies in the studies. AL appears
      more effective at avoiding parasitological failure at days 28 than AS+AQ. 

PMID- 23878698
TI  - Is chloroquine better than artemisinin combination therapy as first line
      treatment in adult nigerians with uncomplicated malaria?-A cost effectiveness
      analysis.
AB  - The current case management and drug policy of malaria in Nigeria recommended by
      the Federal ministry of health may not be appropriate for all age categories.
      This suspicion was tested by running a cost effectiveness analysis of two
      possible and alternative strategies: Artemisinin Combination Therapy (ACT) or
      Chloroquine and ACT only if CQ fails (CANACT), in adult non pregnant Nigerians
      aged 20-45yrs. The result confirms that ACT is indeed more effective but also
      more costly with an incremental cost effectiveness ratio (ICER) of #2,546,527.00
      per QALY that is much higher than the estimated upper limit of #25,000.00 that
      either patients or provider may be willing to pay. The CANACT strategy may be the
      most cost effective strategy in this subgroup of Nigerian patients and also
      provides better value for money. 

PMID- 23878699
TI  - Evaluation of schistosoma mansoni morbidity one year after praziquantel treatment
      in rhino cAMP and obongi in west nile, Uganda.
AB  - An evaluation study on reversibility of Schistosoma mansoni induced periportal
      fibrosis (PF) morbidity following treatment with praziquantel, 40mg/kg body
      weight after one year, was carried out in Rhino Camp and Obongi all are West Nile
      districts in northern Uganda. To assess the reversibility of Schistosoma (S)
      mansoni induced PFs morbidity following treatment with praziquantel, 40mg/kg body
      weight after one year. The design was a Prospective cohorts study; and the
      setting was a busy canoe landing sites along Albert Nile in Schistosoma (S)
      mansoni hyperendemic areas of Rhino Camp and Obongi fishing village were selected
      for the study. Previously in 2005, 1562 people including fishermen and women,
      school pupils, teachers, and civil servants were studied in both fishing villages
      for S. mansoni using Kato/Katz stool smear method. Abdominal ultrasonography and
      sonomorphological abnormalities of periportal fibrosis were performed with Aloka
      portable ultrasound machine (Hellige, Freiburg, Germany) fitted with a convex
      probe of 3.5 mega Hertz was also performed in the field clinic on all patients
      who had S. mansoni eggs in their faeces. The sonomorphological abnormalities of
      periportal fibrosis were categorised and organomorphometry of liver and spleen
      was done. One thousand two hundred and seventy three 1273 (81.5%) patients in
      Rhino Camp and Obongi fishing villages were found to be excreting from 100 to >=
      500 eggs per gram (epg) of faeces of S. mansoni eggs. Two hundred and eighty nine
      (18.5%) did not have eggs of S.mansoni in their faeces. All the 1273 patients
      secreting eggs of S.mansoni in their stool in Rhino Camp and Obongi fishing
      villages had abdominal ultrasonography and sonomorphological abnormalities of
      periportal fibrosis. Eight hundred and forty 840 (66%) although excreted S.
      mansoni eggs in their stool had Pf (0); Pf grade (I), n=259 (20.3%); Pf grade
      (II) n =147 (11.5%); and Pf grade (III) n=27 (2.1%) were observed. 

PMID- 23878700
TI  - [Not Available].

PMID- 23878701
TI  - Sensitivity of microscopy compared to molecular diagnosis of p. Falciparum:
      implications on malaria treatment in epidemic areas in kenya.
AB  - Detection of Plasmodium species by microscopy has been the gold standard for
      diagnosis of malaria for more than a century. Despite the fact that there is a
      significant decline in the number of positive cases reported from microscopy,
      antimalarial drugs prescriptions are on continuous increase as patients present
      with symptoms of malaria. This makes it difficult to establish accuracy,
      sensitivity and specificity of light microscopy in diagnosis of malaria in
      epidemic areas. This study was designed to compare microscopy with polymerase
      chain reaction as diagnostic methods for malaria in three epidemic areas in
      Kenya. A total of 356 patients presenting with malaria symptoms were diagnosed by
      microscopy and dried blood filter paper spots were collected from patient in
      Kisii, West Pokot and Narok districts. Plasmodium falciparum DNA was extracted
      from the dried blood filter samples. Primers specific for the Plasmodium Species
      were designed and used in a two step amplification of the Pfmdr gene. The PCR
      products were analyzed in ethidium bromide stained 1.5% agarose gel. It was found
      that 72 out of 350 specimens diagnosed as negative were positive for P.
      falciparum by nested PCR, while 6 which were microscopy positive were confirmed
      so by nested PCR. This study demonstrates that there is a high level of
      misdiagnosis which may either lead to denial for deserved treatment or undeserved
      treatment. Nested PCR detection of malaria parasites is a very useful complement
      to microscopy although it is expensive and takes long time. Additionally, smear
      negative patients suspected to have malaria should be subjected to PCR diagnosis
      to improve rational drug use. The economic burden of misdiagnosis and
      mistreatment of malaria outweighs that of PCR diagnosis, hence this diagnostic
      mode could be tenable in the long run even in rural areas. 

PMID- 23878702
TI  - Isolated ovarian tuberculosis mimicking ovarian carcinoma: case report and
      literature review.
AB  - Although genitourinary tuberculosis is common, reports of isolated ovarian
      tuberculosis are rare. However, its presentation can mimick that of an ovarian
      tumour, leading to diagnostic difficulties. A woman of 17 years presented with
      chronic pelvic pain, weight loss, a right ovarian mass on ultrasound, and a
      significantly elevated CA-125 level. A diagnosis of ovarian carcinoma was made,
      and laparotomy was performed with resection of the right ovary. Postoperative
      histological examination, however, revealed classic tuberculoid appearances, with
      no signs of malignancy. Antituberculosis treatment was commenced, with full
      resolution of her symptoms and a decrease in CA-125 level. Isolated ovarian
      tuberculosis is most common in young women living in endemic zones. CA-125 can be
      raised in both conditions, and imaging is rarely conclusive. Intraoperative
      frozen section of tissue specimens can be helpful if available. Early diagnosis
      of ovarian tuberculosis is vital as untreated disease can lead to infertility. 

PMID- 23878703
TI  - An analysis of auditory manifestations in a group of adults with AIDS prior to
      antiretroviral therapy.
AB  - The chief objective of the current study was to investigate the auditory status
      in a group of adults with AIDS before commencing antiretroviral therapy (ART) in
      a hospital outpatient clinic in Gauteng, South Africa. A total sample of 150
      participants, aged between 20 and 46 years, was assessed following a prospective
      qualitative research design. All participants underwent case history interviews
      and medical record reviews, otoscopy and tympanometry, as well as conventional
      pure tone audiometry testing. Descriptive statistics was used to analyse data
      obtained. Prevalence, type, degree, configuration, and symmetry of the auditory
      manifestations; as well as type of onset of hearing loss and the possible causes
      of the auditory manifestations were analysed. Findings indicated that auditory
      manifestations in adults with AIDS are varied in nature and are possibly due to a
      number of causes. Manifestations including hearing loss, tinnitus and vertigo (in
      varied combinations) were found; with the types of hearing loss being mainly
      sensorineural in nature. The severity of hearing loss ranged from mild to severe,
      occurred either unilaterally or bilaterally; with the type of onset being mainly
      gradual and progressive in nature. The varied causes of hearing loss included HIV
      infection or AIDS illness as a primary cause, opportunistic infections, and
      various ototoxic therapies that the patients had undergone. Implications for
      future research as well as future assessment and management of patients with AIDS
      are raised. 

PMID- 23878704
TI  - Spectrum of Clinical Presentations in Human Immunodeficiency Virus (HIV) Infected
      Patients with Renal Disease.
AB  - HIV infection is a multiorgan disease with the kidney not spared. A variety of
      renal syndromes with varying clinical presentations has been reported amongst HIV
      infected patients. This study aims to highlight the spectrum of clinical
      presentations in HIV infected patients with renal disease. HIV infected patients
      presenting at University of Benin Teaching Hospital (UBTH) Benin City were the
      study population. A total of 383 patients were studied. Their biodata, clinical
      presentations and laboratory investigations including serum urea, creatinine and
      albumin, urine protein and creatinine were assessed. Their glomerular filtration
      rate (GFR) and protein urine excretion were calculated using six equations of
      modification of diet in renal disease (MDRD) and protein: creatinine ratio
      respectively. Patients were stratified according to their renal functions into
      normal, mild, moderate and severe renal function impairment. The data was
      analysed using statistical software program SPSS Vs 15.0. 53.3% of 383 patients
      screened had renal function impairment, 40.2% mild, 37.7% moderate and 22.2%
      severe impairment. Mean age was 35.6+/-8.3, 36.0+/-9.9 and 36.3+/-8.3 years for
      mild, moderate and severe renal function impairment (RFI) respectively. Easy
      fatigability was the commonest symptoms occurring in 47.5%, 30.0%, 37.5% and
      22.5% of control, mild RFI, moderate RFI and severe RFI subjects respectively (p
      = 0.568). Oliguria, facial and body swelling occurred more in patients with RFI
      especially in patients with severe renal impairment. The difference is
      statistically significant (p = 0.046, 0.041, and 0.033 respectively). Pallor was
      the commonest clinical sign occurring in 32.5%, 50.0%, 35.0% and 62.5% of control
      and patients with mild, moderate, and severe RFI respectively; the difference was
      not statistically significant (p = 0.459). Ascites, facial puffiness and pedal
      oedema were commoner in patients with RFI especially those with severe RFI. The
      differences were statistically significant. (p = 0.048, 0.019, and 0.008
      respectively). In conclusion spectrum of clinical presentations in HIV patients
      with renal impairment are many but few are specific to these patients. 

PMID- 23878705
TI  - Evidence of long term benefit of morbidity reduction due to praziquantel
      treatment against schistosoma mansoni in kigungu fishing village in entebbe,
      Uganda.
AB  - Praziquantel (PZQ) is efficacious against Schistosoma mansoni. This was
      prospective cohort study. This study was carried out at Kigungu fishing village,
      Entebbe, Uganda. The goal of the study was to establish cost effective regiment
      for mass drug administration (MDA) of Praziquentel in the morbidity reduction of
      S.mansoni infection. In January 2004, nine hundred and forty five (945)
      participants were registered in this study. Our analysis was based on examining
      microscopically three slides prepared from each of 945 stool specimens delivered
      by each of the participant using modified Kato/Katz method. These included male
      and female, children and adults living in Kigungu fishing village in Entebbe
      Uganda. In total 901, cohorts were re-examined for infections clearance six
      months later in July 2004 and 18 months later in June 2005, 625 cohorts were
      again re-evaluated for S.mansoni infections after the baseline study. At
      baseline, (448) of 945 (47.5%) cohorts were S. mansoni positive. All these
      participants were treatment with a single oral dose of praziquantel at 40mg/kg.
      At the same time, 495 (52.5%) were S. mansoni negative. Of the 625 (66.3%)
      cohorts who came back for final review, 80 (12.8%) were still positive for S.
      mansoni while 210 (33.6%) remained negative after the base line treatment with
      praziquantel. On the other hand 103 (16.3%) of cohorts who were initially
      negative at the base line became S.mansoni positive after 18 months and
      213(34.1%) remained negative for S.mansoni. The force of re-infection after six
      months was significant {(P=0.0001), (OR 0.47) CI at 95% (0.31-0.71)}.
      Nevertheless the force of reinfection was not significant after 18 months
      {(P=0.766), (OR 0.95) CI at 95% (0.68-1.34)}.The geometric mean eggs excretion of
      the 80 cohorts who were S.mansoni positive at 18 months was 151.967.This did not
      reach the geometric mean egg excreted by the same cohorts at baseline which was
      285.05. The egg excretion was reduced by 46.8%. Similarly there was marked
      decrease in clinical symptoms amongst the cohorts. Our study suggests evidence of
      long-term benefit of praziquantel in Kigungu and that a yearly administration of
      praziquantel to the community could be a regiment for mass drug administration
      (MAD) for this community to control schistosomiasis morbidity. 

PMID- 23878706
TI  - Prevalence of hospital-acquired enterococci infections in two primary-care
      hospitals in osogbo, southwestern Nigeria.
AB  - Enterococci are opportunistic bacteria that become pathogenic when they colonize
      niches where they are not normally found. Of recent, they have become major cause
      of nosocomial infections, especially of the bloodstream, urinary tract and
      surgical sites. The aim of this study is to determine the point-prevalence rate
      of human enterococci infections among hospitalized patients in Osogbo, Nigeria.
      The study was conducted between January and June 2009 in two primary-care
      hospitals in Osogbo and involved a total of 118 patients who developed clinical
      evidence of infection at least 48 hours after hospital admission. Appropriate
      clinical samples were collected from the patients after an informed consent and
      cultured for isolation/biochemical identification of Enterococcus species at the
      Bacteriology Laboratory of Ladoke Akintola University of Technology, Osogbo using
      standard microbiological methods. There were 525 hospital admissions within the
      time frame of the study of which 118 (22.5%) developed hospital acquired
      infection (HAI); 58 (49.2%) of which cultured positive for bacterial pathogens.
      Enterococci were isolated from infective focus in 7 patients, giving a prevalence
      rate of hospital-acquired enterococci infection of 5.9%. Two species of
      Enterococcus were identified; Enterococcus faecalis from urinary tract infection
      (UTI) and surgical site infection (SSI) of 6 (85.7%) patients and Enterococcus
      faecium from UTI in 1 (14.3%) patient. Other bacteria recovered from other
      infective foci were Klebsiella spp 31.0%, Pseudomonas spp 20.7%, Staphylococcus
      aureus 17.2%, Escherichia coli 12.1%, Staphylococcus epidermidis 3.4%,
      Streptococcus pneumoniae 1.7% and Serratia spp 1.7%. All the enterococci isolates
      were multiply antibiotic resistant, and 42.9% were vancomycin-resistant
      enterococci (VRE) with the VRE strains showing resistance to wider range of
      antibiotics than the vancomycin-sensitive strains. Other Gram-positive and Gram
      negative bacterial isolates also demonstrated multiple resistance to all commonly
      available antibiotics in this community except E. coli and Pseudomonas spp which
      were relatively sensitive to ciprofloxacin and ceftazidime. This limited study
      demonstrated a high prevalence rate of multiple antibiotic resistant enterococci
      infections among hospitalized patients in this environment. There is need for
      systematic surveillance of hospitals for enterococci infections; prudent use and
      rational prescription of antibiotics and stringent measures to reduce the
      prevalence rate by health education on infection control measures such as
      isolation, cleaning, disinfection and sterilization. 

PMID- 23878707
TI  - Clinical epidemiology of lymphatic filariasis and community practices and
      perceptions amongst the ado people of benue state, Nigeria.
AB  - As part of efforts to initiate lymphatic filariasis elimination activities in
      Benue State, this study employed the use of lymphatic filariasis-related clinical
      signs as rapid diagnostic features, immunochromatographic card test (ICT) to
      detect circulating filarial antigen (CFA) and questionnaire to investigate
      community perceptions and beliefs. 81 (32.6%) out of the 248 persons were
      positive for circulating filarial antigen (CFA). Infection rates denoted by CFA
      ranged from 41 (46.1%) in Uffia to 1(6.6%) in Ijigbam districts. Distribution of
      community ICT prevalence showed a significant variation (X(2), P < 0.05). The
      prevalence of clinical signs and/or symptoms in the communities also showed
      significant variations (X(2), P < 0.05). Community hydrocoele prevalence ranged
      from 8 (9.0%) in Uffia to 1(6.6%) in Ijigbam. The overall hydrocoele prevalence
      was 21 (8.5%), while the overall lymphoedema prevalence was 16 (6.4%) and women
      accounted for 14 (87.5%) of persons with swollen limbs. Only about 14 (15.9%) of
      unaffected respondents knew that lymphatic filariasis is transmitted through
      mosquito bites, this differ significantly from affected respondents 10 (66.6%)
      (X(2), P < 0.05). The communities' capacity to protect themselves is hindered by
      a lack of understanding of the true cause, symptoms, transmission route and
      prevention of the disease. Our study demonstrates the need for the development of
      health education programmes that will enable people to protect themselves against
      mosquito bites. As Nigeria commence her lymphatic filariasis elimination
      programmes, there is an urgent need to develop morbidity management activities
      that will alleviate the burden of patients. 

PMID- 23878708
TI  - Astrovirus infection in children in lagos, Nigeria.
AB  - A preliminary investigation was conducted to screen for astrovirus in Lagos. Two
      hundred and fifteen (215) faecal samples collected from children under 5 years
      old with diarrhoea (161) and without diarrhoea (54) admitted at paediatric
      clinics in Lagos State were studied. The stool specimens were examined for the
      presence of human astrovirus antigen using a monoclonal antibody-based ELISA
      (Astrovirus RIDASCREEN((r)) r-Biopharm, Germany) technique. Astrovirus was
      detected in 40.4 percent (65/161) of the diarrhoeal stools compared to 11.1
      percent (6/54) of the control specimens. Astrovirus was found to infect younger
      children and about three quarter of the children infected was under 12 months of
      age. The prevalence of infection decreases with age group and was statistically
      significant (P = 0.0470). Although, prevalence of infection is more in males than
      females but this is not significant. This study shows that astrovirus is an
      important agent of acute gastroenteritis among children in Lagos state. 

PMID- 23878709
TI  - Leprosy Elimination: Progress and Challenges in Nigeria; Kaduna State TB and
      Leprosy Control Programme as a Case Study.
AB  - The study aims at describing the achievements and challenges of Leprosy control
      in Kaduna State using appropriate indicators. The study was a five year (2004
      2008) retrospective review of the Leprosy records and annual reports of all the
      twenty three LGAs in Kaduna State. Various Leprosy indicators were calculated and
      presented in different graphic presentations. Focus group discussions were
      organised with the aim of identifying current challenges of Leprosy control in
      the State. There was a decline in the new Leprosy cases detected annually from
      226 cases in 2004 to 140 cases in 2008. The prevalence rate ranged between 0.3
      0.4 per 10,000 population within the five year period. The proportion of children
      among new cases dropped from 12% in 2004 to 5% in 2007 and increased to 9% in
      2008. Grade 2 disability among new cases was very high (between 21%-27%) within
      the same period. Leprosy elimination target has been achieved in Kaduna State,
      but new cases with high proportion of children and WHO grade 2 disability were
      still been reported. 

PMID- 23878710
TI  - Quality of medical laboratory services in resource-limited settings.
AB  - This report endorses the author's own views on the subject after taking up a
      laboratory adviser mission in Africa. Taking the example of laboratory services
      practice in sub-Saharan countries, it is shown that diagnosis of diseases which
      require the use of laboratory suffer from lapses in the quality of case-detection
      and case-reporting. These services lack management and an information system that
      limits the set up of a laboratory network at national level. An efficient health
      program set in resource deprived countries would then yield improvements on
      systems and infrastructure. 

PMID- 23878711
TI  - HIV/AIDS Stigmatization, the Reason for Poor Access to HIV Counseling and Testing
      (HCT) Among the Youths in Gulu (Uganda).
AB  - HIV/AIDS-related stigma still exists in many communities in Uganda. Stigma
      perpetuates discrimination and this may be a key contributor to the spread of
      HIV/AIDS in this country. Right from the beginning, HIV/AIDS epidemic has been
      accompanied with fear, ignorance and denial, leading to stigmatization and
      discrimination against people living with HIV/AIDS and their families. A study
      conducted by Uganda AIDS Commission (UAC) in Uganda indicated that 64% of the
      people who tested for HIV/AIDS did not disclose status to their partners due to
      fear of stigmatization. A cross-sectional study was conducted in Gulu District,
      Pece sub County among the youths 15 to 35 years old. A structured questionnaire
      was administered to 86 consented youths who were consecutively selected. Ethical
      approval was obtained from Gulu Hospital. Most youths (90%) practiced
      stigmatization, (93.1%) respondents had adequate knowledge on HIV counseling and
      testing (HCT). However, only (36.1%) had undertaken HCT and the majority did not
      do because of fear of stigmatization. There is sufficient knowledge, a positive
      attitude but a poor practice to HCT. There is high level of HIV/AIDS
      stigmatization among the youths. 

PMID- 23878712
TI  - Community participation in malaria control in olorunda local government area,
      osun state, southwestern Nigeria.
AB  - Malaria is a major health burden in developing countries and needs multiple
      strategies for its control. Community participation as one of the strategies for
      malaria control promotes self-awareness and confidence, causes the people to
      examine the problems and to think positively about the solutions. The study was
      aimed at assessing the level of community participation in malaria control in
      Olorunda local government area of Osogbo, Osun state, Nigeria. The study employed
      a cross-sectional descriptive design. Multi-staged sampling technique was used to
      choose 550 respondents. An interviewer-administered semi-structured questionnaire
      was used to elicit information from the respondents. Most of the respondents
      (65.0%) fell between the age ranges 20-39 years, with a mean age of 32.85 +/- 12
      years. Almost all (98.4%) respondents had knowledge of malaria with most of them
      (88.0%) correctly aware that mosquito bite could lead to malaria fever.
      Respondents stated that stagnant pool (92.6%) and refuse dump (89.0%) could
      predispose to malaria. About two-thirds (60.6%) of the respondents participated
      in the control of the breeding sites of mosquitoes on specific days for
      environmental sanitation. The association between community participation in
      health talk and community participation in malaria control was statistically
      significant (p<0.000). Although only 23.0% use ITN to protect themselves from
      mosquito bites, there was statistical significant association between awareness
      of respondents about ITN and its usage (p=0.003). Knowledge of respondents about
      malaria was high with majority participating in malaria control measures.
      However, the use of insecticide treated nets (ITN) was low. Therefore, it is
      recommended that continuous awareness creation on the use of ITN, and continued
      efforts aimed at elimination of breeding sites of mosquitoes should be adopted to
      achieve long term control of malaria. 

PMID- 23878713
TI  - Advances in the Diagnosis, Treatment and Control of HIV Associated Tuberculosis.
AB  - There has been an increase in the number of published tuberculosis/HIV (TB/HIV)
      research findings in recent times. The potential impact of these findings on
      routine care has informed this review which aims at discussing current concepts
      and practices underpinning TB/HIV care and control. Any HIV infected person with
      a cough of any duration is currently considered a TB suspect. Preliminary results
      also show that the diagnostic yield of same day sputum samples (front loading) is
      comparable to two-day samples. Laboratory diagnosis is shifting from Ziehl
      Neelsen (ZN) smear microscopy and solid culture to fluorescent microscopy,
      molecular tests and liquid culture. Concomitant TB/HIV therapy improves survival
      and WHO has recommended ART for all TB/HIV patients. Unless CD4 cell counts are
      less than 50 cells/ul, ART can be deferred until end of intensive phase. Evidence
      of survival benefit at high CD4 cell counts is still lacking. New TB drugs and
      treatment shortening studies are underway but so far no new TB drugs has been
      added to the current arsenal and treatment duration still remains six months or
      more. WHO has recommended the 31s (intensified TB case finding, isoniazid
      prophylaxis and infection control) for TB/HIV control in addition to effective
      therapy, Antiretroviral therapy and TB vaccines. There has been immense progress
      in TB/HIV research, however optimal management of HIV-Infected TB patients, will
      require further research and appropriate translation of emerging evidence to
      policy and practice. 

PMID- 23878714
TI  - The Expression of Interleukin-1b and miRNA-146a in the Cerebral Cortex of Acute
      Escherichia Coli Meningitis Immature Rat Model.
AB  - The main limitation to advances in treatment of bacterial meningitis and its
      complications is the incomplete knowledge of the pathogenesis and pathophysiology
      of this disease. The aim of this research is to detect the expression of
      interleukin (IL)-1beta as pro-inflammatory cytokine and miRNA (miR)-146a as post
      transcriptional inflammation associated microRNA (miRNA) in the cerebral cortex
      of acute Escherichia coli (E. coli) meningitis immature rat model. Immature rats
      in the post natal day 11 (PN11) were used to construct a model of acute E. coli
      meningitis and served as controls. The expression of IL-1beta and miR-146a were
      detected in the cerebral cortex by reverse transcription polymerase chain
      reaction (RT-PCR) and real-time quantitative PCR (qPCR) analysis respectively, 24
      hours after bacterial inoculation. In the cerebral cortical tissue of acute E.
      coli meningitis immature rat model the IL-1beta expression was significantly
      upregulated while the miR-146a expression was significantly downregulated. This
      study tried to add a new insight on the molecular basis of the E. coli meningitis
      pathogenesis at its very early stage through detecting the expression of IL-1beta
      and miR-146a in the cerebral cortex of the infected immature rats. Consequently,
      modulation of the IL-1beta- miR-146a axis may be a new target for treatment of
      acute E. coli meningitis. 

PMID- 23878715
TI  - Association of HIV-Induced Immunosuppression and Clinical Malaria in Nigerian
      Adults.
AB  - Despite the growing body of evidence on the interaction between HIV and malaria
      in sub-Saharan Africa, there is a dearth of data on clinical malaria in HIV
      infected patients in Nigeria. We determined the burden of clinical malaria in HIV
      infected adult Nigerians and further investigated the association between their
      immunological status and the rates of clinical malaria. Ninety seven
      antiretroviral treatment-naive HIV-infected adults were enrolled in a cross
      sectional study from August to December, 2009. The participants had a complete
      clinical evaluation, thick and thin blood films for malaria parasites and CD4
      cell count quantification. Clinical malaria was defined as having fever
      (temperature >= 37.5 degrees C or history of fever within 48 hours) and a malaria
      parasite density above the median value obtained for subjects with co-existing
      fever and parasitaemia. Clinical malaria was diagnosed in 10 out of 97 patients
      (10.3%). Lower CD4 cell counts were associated with increasing rates of clinical
      malaria which was 0% at CD4 cell count of >= 500, 2.6% at 200-499 and 30% at <200
      cells/uL (chi(2) = 18.3, p = 0.0001). This association remained significant after
      controlling for other factors in a multivariate analysis (AOR=22.98, 95% C.I:
      2.62-20.14, p = 0.005). An inverse relationship between CD4 cell count and
      parasite density was demonstrated (regression co-efficient = - 0.001, p =
      0.0002). More aggressive malaria control measures are highly needed in severely
      immunosuppressed HIV-infected patients. 

PMID- 23878716
TI  - A chemical synthesis of 11-methoxy mitragynine pseudoindoxyl featuring the
      interrupted Ugi reaction.
AB  - A synthesis of 11-methoxy mitragynine pseudoindoxyl, a new member of the
      mitragynine class of opioid agonists, from a derivative of the Geissman-Waiss
      lactone is described. An internal attack of an electron-rich aromatic ring on an
      electrophilic nitrilium ion and a late-stage construction of the functionalized
      piperidine ring by the method of reductive cyclization are the pivotal
      transformations; both ring annulations proceed in a highly diastereoselective
      fashion. The construction of substituted indoxyl frameworks by the interrupted
      Ugi method offers an attractive alternative to the strategy of oxidatively
      rearranging indoles.

PMID- 23878717
TI  - Carbene-Stabilized Main Group Radicals and Radical Ions.
AB  - Shortly after their discovery at the end of the 80s, stable singlet carbenes have
      been recognized as excellent ligands for transition metal based catalysts, and as
      organo-catalysts in their own right. At the end of the 2000s, it has been shown
      that they can coordinate main group elements in their zero oxidation state, and
      even activate small molecules. This review covers examples in the literature
      dealing with the most recent application of stable singlet carbenes, namely their
      use to stabilize radicals and radical ions that are otherwise unstable.

PMID- 23878718
TI  - Peptide-based Targeting of Fluorescent Zinc Sensors to the Plasma Membrane of
      Live Cells.
AB  - Combining fluorescent zinc sensors with the facile syntheses and biological
      targeting capabilities of peptides, we created green- and blue-emitting probes
      that, (i) are readily prepared on the solid-phase, (ii) retain the photophysical
      and zinc-binding properties of the parent sensor, and (iii) can be directed to
      the extracellular side of plasma membranes in live cells for detection of mobile
      zinc.

PMID- 23878719
TI  - DNA-polyfluorophore Chemosensors for Environmental Remediation: Vapor-phase
      Identification of Petroleum Products in Contaminated Soil.
AB  - Contamination of soil and groundwater by petroleum-based products is an extremely
      widespread and important environmental problem. Here we have tested a simple
      optical approach for detecting and identifying such industrial contaminants in
      soil samples, using a set of fluorescent DNA-based chemosensors in pattern-based
      sensing. We used a set of diverse industrial volatile chemicals to screen and
      identify a set of five short oligomeric DNA fluorophores on PEG-polystyrene
      microbeads that could differentiate the entire set after exposure to their vapors
      in air. We then tested this set of five fluorescent chemosensor compounds for
      their ability to respond with fluorescence changes when exposed to headgas over
      soil samples contaminated with one of ten different samples of crude oil,
      petroleum distillates, fuels, lubricants and additives. Statistical analysis of
      the quantitative fluorescence change data (as Delta(R,G,B) emission intensities)
      revealed that these five chemosensors on beads could differentiate all ten
      product mixtures at 1000 ppm in soil within 30 minutes. Tests of sensitivity with
      three of the contaminant mixtures showed that they could be detected and
      differentiated in amounts at least as low as one part per million in soil. The
      results establish that DNA-polyfluorophores may have practical utility in
      monitoring the extent and identity of environmental spills and leaks, while they
      occur and during their remediation.

PMID- 23878720
TI  - Concise Total Synthesis of (+)-Bionectins A and C.
AB  - The concise and efficient total synthesis of (+)-bionectins A and C is described.
      Our approach to these natural products features a new and scalable method for
      erythro-beta-hydroxytryptophan amino acid synthesis, an intramolecular Friedel
      Crafts reaction of a silyl-tethered indole, and a new mercaptan reagent for
      epipolythiodiketopiperazine (ETP) synthesis that can be unravelled under very
      mild conditions. In evaluating the impact of C12-hydroxylation, we have
      identified a unique need for an intramolecular variant of our Friedel-Crafts
      indolylation chemistry. Several key discoveries including the first example of
      permanganate-mediated stereoinvertive hydroxylation of the alpha-stereocenters of
      diketopiperazines as well as the first example of a direct triketopiperazine
      synthesis from a parent cyclo-dipeptide are discussed. Finally, the synthesis of
      (+)-bionectin A and its unambiguous structural assignment through X-ray analysis
      provides motivation for the reevaluation of its original characterization data
      and assignment.

PMID- 23878721
TI  - Integrative genomic analysis of the human immune response to influenza
      vaccination.
AB  - Identification of the host genetic factors that contribute to variation in
      vaccine responsiveness may uncover important mechanisms affecting vaccine
      efficacy. We carried out an integrative, longitudinal study combining genetic,
      transcriptional, and immunologic data in humans given seasonal influenza vaccine.
      We identified 20 genes exhibiting a transcriptional response to vaccination,
      significant genotype effects on gene expression, and correlation between the
      transcriptional and antibody responses. The results show that variation at the
      level of genes involved in membrane trafficking and antigen processing
      significantly influences the human response to influenza vaccination. More
      broadly, we demonstrate that an integrative study design is an efficient
      alternative to existing methods for the identification of genes involved in
      complex traits. DOI:http://dx.doi.org/10.7554/eLife.00299.001. 

PMID- 23878722
TI  - The insulin receptor cellular IRES confers resistance to eIF4A inhibition.
AB  - Under conditions of stress, such as limited growth factor signaling, translation
      is inhibited by the action of 4E-BP and PDCD4. These proteins, through inhibition
      of eIF4E and eIF4A, respectively, impair cap-dependent translation. Under stress
      conditions FOXO transcription factors activate 4E-BP expression amplifying the
      repression. Here we show that Drosophila FOXO binds the PDCD4 promoter and
      stimulates the transcription of PDCD4 in response to stress. We have shown
      previously that the 5' UTR of the Drosophila insulin-like receptor (dINR)
      supports cap-independent translation that is resistant to 4E-BP. Using
      hippuristanol, an eIF4A inhibitor, we find that translation of dINR UTR
      containing transcripts are also resistant to eIF4A inhibition. In addition, the
      murine insulin receptor and insulin-like growth factor receptor 5' UTRs support
      cap-independent translation and have a similar resistance to hippuristanol. This
      resistance to inhibition of eIF4E and eIF4A indicates a conserved strategy to
      allow translation of growth factor receptors under stress conditions.
      DOI:http://dx.doi.org/10.7554/eLife.00542.001. 

PMID- 23878723
TI  - Her2 activation mechanism reflects evolutionary preservation of asymmetric
      ectodomain dimers in the human EGFR family.
AB  - The receptor tyrosine kinase Her2, an intensely pursued drug target, differs from
      other members of the EGFR family in that it does not bind EGF-like ligands,
      relying instead on heterodimerization with other (ligand-bound) EGFR-family
      receptors for activation. The structural basis for Her2 heterodimerization,
      however, remains poorly understood. The unexpected recent finding of asymmetric
      ectodomain dimer structures of Drosophila EGFR (dEGFR) suggests a possible
      structural basis for Her2 heterodimerization, but all available structures for
      dimers of human EGFR family ectodomains are symmetric. Here, we report results
      from long-timescale molecular dynamics simulations indicating that a single
      ligand is necessary and sufficient to stabilize the ectodomain interface of Her2
      heterodimers, which assume an asymmetric conformation similar to that of dEGFR
      dimers. This structural parallelism suggests a dimerization mechanism that has
      been conserved in the evolution of the EGFR family from Drosophila to human.
      DOI:http://dx.doi.org/10.7554/eLife.00708.001. 

PMID- 23878724
TI  - An essential and NSF independent role for alpha-SNAP in store-operated calcium
      entry.
AB  - Store-operated calcium entry (SOCE) by calcium release activated calcium (CRAC)
      channels constitutes a primary route of calcium entry in most cells. Orai1 forms
      the pore subunit of CRAC channels and Stim1 is the endoplasmic reticulum (ER)
      resident Ca(2+) sensor. Upon store-depletion, Stim1 translocates to domains of ER
      adjacent to the plasma membrane where it interacts with and clusters Orai1
      hexamers to form the CRAC channel complex. Molecular steps enabling activation of
      SOCE via CRAC channel clusters remain incompletely defined. Here we identify an
      essential role of alpha-SNAP in mediating functional coupling of Stim1 and Orai1
      molecules to activate SOCE. This role for alpha-SNAP is direct and independent of
      its known activity in NSF dependent SNARE complex disassembly. Importantly, Stim1
      Orai1 clustering still occurs in the absence of alpha-SNAP but its inability to
      support SOCE reveals that a previously unsuspected molecular re-arrangement
      within CRAC channel clusters is necessary for SOCE.
      DOI:http://dx.doi.org/10.7554/eLife.00802.001. 

PMID- 23878725
TI  - MYBL2 is a sub-haploinsufficient tumor suppressor gene in myeloid malignancy.
AB  - A common deleted region (CDR) in both myelodysplastic syndromes (MDS) and
      myeloproliferative neoplasms (MPN) affects the long arm of chromosome 20 and has
      been predicted to harbor a tumor suppressor gene. Here we show that MYBL2, a gene
      within the 20q CDR, is expressed at sharply reduced levels in CD34+ cells from
      most MDS cases (65%; n = 26), whether or not they harbor 20q abnormalities. In a
      murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of
      normal levels in multipotent hematopoietic progenitors resulted in clonal
      dominance of these 'sub-haploinsufficient' cells, which was reflected in all
      blood cell lineages. By 6 months post-transplantation, the reconstituted mice had
      developed a clonal myeloproliferative/myelodysplastic disorder originating from
      the cells with aberrantly reduced Mybl2 expression. We conclude that
      downregulation of MYBL2 activity below levels predicted by classical
      haploinsufficiency underlies the clonal expansion of hematopoietic progenitors in
      a large fraction of human myeloid malignancies.
      DOI:http://dx.doi.org/10.7554/eLife.00825.001. 

PMID- 23878726
TI  - Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity
      of amyloid beta.
AB  - Amyloid protein aggregates are associated with dozens of devastating diseases
      including Alzheimer's, Parkinson's, ALS, and diabetes type 2. While structure
      based discovery of compounds has been effective in combating numerous infectious
      and metabolic diseases, ignorance of amyloid structure has hindered similar
      approaches to amyloid disease. Here we show that knowledge of the atomic
      structure of one of the adhesive, steric-zipper segments of the amyloid-beta
      (Abeta) protein of Alzheimer's disease, when coupled with computational methods,
      identifies eight diverse but mainly flat compounds and three compound derivatives
      that reduce Abeta cytotoxicity against mammalian cells by up to 90%. Although
      these compounds bind to Abeta fibers, they do not reduce fiber formation of
      Abeta. Structure-activity relationship studies of the fiber-binding compounds and
      their derivatives suggest that compound binding increases fiber stability and
      decreases fiber toxicity, perhaps by shifting the equilibrium of Abeta from
      oligomers to fibers. DOI:http://dx.doi.org/10.7554/eLife.00857.001. 

PMID- 23878727
TI  - Immune response is a personal matter.
AB  - Changes in gene expression could be used to predict whether individuals will
      respond successfully to the influenza vaccine. 

PMID- 23878728
TI  - Lifting the veil on amyloid drug design.
AB  - High resolution structures and computational methods have been used to identify
      compounds that prevent amyloid fibrils associated with Alzheimer's disease from
      dissociating into toxic species. 

PMID- 23878729
TI  - A recipe for mediocrity and disaster, in five axioms.
AB  - Biomedical research in the US will become unsustainable unless scientists and
      research institutions start to question certain assumptions they have long taken
      for granted. 

PMID- 23878730
TI  - Therapeutic hypothermia, still "too cool to be true?".
AB  - Therapeutic hypothermia, an intervention reducing core body temperature below 35
      degrees Celsius, has gained popularity in the management of acute brain injury
      after a series of small clinical trials in patients following cardiac arrest,
      stroke and traumatic brain injury. This article reviews the evidence relating to
      therapeutic hypothermia as an intervention in acute injury. 

PMID- 23878731
TI  - An amino acids mixture improves the hepatotoxicity induced by acetaminophen in
      mice.
AB  - Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high
      dose it leads to undesirable side effects, such as hepatotoxicity and
      nephrotoxicity. The aim of this study was to evaluate the protective role of DDM
      GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2 :
      1 : 1, in comparison to N-acetylcysteine (NAC), against acetaminophen- (APAP-)
      induced hepatotoxicity in mice. Toxicity was induced in mice by the
      intraperitoneal (ip) administration of low dose (2 mmol/kg) or high dose (8
      mmol/kg) of APAP. DDM-GSH (0.4 to 1.6 mmol/kg) was given ip to mice 1 h before
      the APAP administration. The same was done with NAC (0.9 to 3.6 mmol/kg), the
      standard antidote of APAP toxicity. Mice were sacrificed 8 h after the APAP
      injection to determine liver weight, serum alanine aminotransferase (ALT), and
      total glutathione (GSH) depletion and malondialdehyde (MDA) accumulation in liver
      tissues. DDM-GSH improved mouse survival rates better than NAC against a high
      dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner
      not only APAP-induced increases of ALT but also APAP-induced hepatic GSH
      depletion and MDA accumulation. Our results suggest that DDM-GSH may be more
      potent than NAC in protecting the liver from APAP-induced liver injury. 

PMID- 23878732
TI  - Psychometric Properties of the Attitudes toward Self-Revised in Italian Young
      Adults.
AB  - Objectives and Methods. Several researchers have provided support for the
      critical role of cognitive vulnerabilities in the development of depression. The
      Attitudes toward Self-Revised (ATS-R) was designed to assess three potential self
      regulatory vulnerabilities to depression: High Standards (HS), Self-Criticism
      (SC), and Negative Generalization (NG). The aim of the study was to assess the
      psychometric properties of the ATS-R in the Italian young adult population. The
      ATS-R, the Beck Depression Inventory-II (BDI-II), the Beck Hopelessness Scale
      (BHS), and the Teate Depression Inventory (TDI) were administered to 857 (320 men
      and 537 women) young adults. Results. The best-fitting solution for the ATS-R was
      a 2-factor model, which obtained satisfactory homogeneity of content (HS/SC:
      Cronbach alpha = 0.81; mean interitem correlation = 0.46. NG: Cronbach alpha =
      0.75; mean interitem correlation = 0.43) and significant correlation with the BDI
      II (NG: Pearson r = 0.29, P < 0.01), the TDI (HS/SC: Pearson r = -0.26, P <
      0.01), and the BHS (HS/SC: Pearson r = -0.29, P < 0.01; NG: Pearson r = 0.22, P <
      0.01). Conclusions. The Italian version of the ATS-R seems to be a valid
      instrument for the study of the role of cognitive tendencies as potential
      vulnerability for depression. 

PMID- 23878733
TI  - A Time Off Incentive Was Not Associated with Influenza Vaccination Acceptance
      among Healthcare Workers.
AB  - Objectives. The national influenza vaccination rate among healthcare workers
      (HCWs) remains low despite clear benefits to patients, coworkers, and families.
      We sought to evaluate formally the effect of a one-hour time off incentive on
      attitudes towards influenza vaccination during the 2011-2012 influenza season.
      Methods. All HCWs at the Philadelphia Veterans Affairs (VA) Medical Center were
      invited to complete an anonymous web-based survey. We described respondents'
      characteristics and attitudes toward influenza vaccination and determined the
      relationship of specific attitudes with respondents' acceptance of influenza
      vaccination, using a 5-point Likert scale. Results. We analyzed survey responses
      from 154 HCWs employed at the Philadelphia VA Medical Center, with a response
      rate of 8%. Among 121 respondents who reported receiving influenza vaccination,
      34 (28%, 95% CI 20-37%) reported agreement with the statement that the time off
      incentive made a difference in their decision to accept influenza vaccination.
      Conclusions. Our study provides evidence that modest incentives such as one-hour
      paid time off will be unlikely to promote influenza vaccination rates within
      medical facilities. More potent interventions that include mandatory vaccination
      combined with penalties for noncompliance will likely provide the only means to
      achieve near-universal influenza vaccination among HCWs. 

PMID- 23878734
TI  - Neonatal intensive care and child psychiatry inpatient care: do different working
      conditions influence stress levels?
AB  - Introduction. Nurses often experience work-related stress. High stress can
      negatively affect job satisfaction and lead to emotional exhaustion with risk of
      burnout. Aim. To analyse possible differences in biological stress markers,
      psychosocial working conditions, health, and well-being between nurses working in
      two different departments. Methods. Stress was evaluated in nurses working in a
      neonatal intensive care unit (NICU) (n = 33) and nurses working in a child and
      adolescent psychiatry inpatient ward (CAP) (n = 14) using salivary cortisol and
      HbA1c. Salivary cortisol was measured three times a day on two consecutive days
      during two one-week periods, seven weeks apart (= 12 samples/person).
      Psychosocial working conditions, health, and well-being were measured once.
      Results. NICU nurses had better social support and more self-determination. CAP
      nurses had a lower salivary cortisol quotient, poorer general health, and higher
      client-related burnout scores. Conclusion. When comparing these nurses with
      existing norm data for Sweden, as a group their scores reflect less work-related
      stress than Swedes overall. However, the comparison between NICU and CAP nurses
      indicates a less healthy work situation for CAP nurses. Relevance to Clinical
      Practice. Healthcare managers need to acknowledge the less healthy work situation
      CAP nurses experience in order to provide optimal support and promote good
      health. 

PMID- 23878735
TI  - Nitric oxide in cerebral vasospasm: theories, measurement, and treatment.
AB  - In recent decades, a large body of research has focused on the role of nitric
      oxide (NO) in the development of cerebral vasospasm (CV) following subarachnoid
      hemorrhage (SAH). Literature searches were therefore conducted regarding the role
      of NO in cerebral vasospasm, specifically focusing on NO donors, reactive
      nitrogen species, and peroxynitrite in manifestation of vasospasm. Based off the
      assessment of available evidence, two competing theories are reviewed regarding
      the role of NO in vasospasm. One school of thought describes a deficiency in NO
      due to scavenging by hemoglobin in the cisternal space, leading to an NO
      signaling deficit and vasospastic collapse. A second hypothesis focuses on the
      dysfunction of nitric oxide synthase, an enzyme that synthesizes NO, and
      subsequent generation of reactive nitrogen species. Both theories have strong
      experimental evidence behind them and hold promise for translation into clinical
      practice. Furthermore, NO donors show definitive promise for preventing vasospasm
      at the angiographic and clinical level. However, NO augmentation may also cause
      systemic hypotension and worsen vasospasm due to oxidative distress. Recent
      evidence indicates that targeting NOS dysfunction, for example, through
      erythropoietin or statin administration, also shows promise at preventing
      vasospasm and neurotoxicity. Ultimately, the role of NO in neurovascular disease
      is complex. Neither of these theories is mutually exclusive, and both should be
      considered for future research directions and treatment strategies. 

PMID- 23878736
TI  - Gray Matter Pathology in MS: Neuroimaging and Clinical Correlations.
AB  - It is abundantly clear that there is extensive gray matter pathology occurring in
      multiple sclerosis. While attention to gray matter pathology was initially
      limited to studies of autopsy specimens and biopsies, the development of new MRI
      techniques has allowed assessment of gray matter pathology in vivo. Current MRI
      techniques allow the direct visualization of gray matter demyelinating lesions,
      the quantification of diffuse damage to normal appearing gray matter, and the
      direct measurement of gray matter atrophy. Gray matter demyelination (both focal
      and diffuse) and gray matter atrophy are found in the very earliest stages of
      multiple sclerosis and are progressive over time. Accumulation of gray matter
      damage has substantial impact on the lives of multiple sclerosis patients; a
      growing body of the literature demonstrates correlations between gray matter
      pathology and various measures of both clinical disability and cognitive
      impairment. The effect of disease modifying therapies on the rate accumulation of
      gray matter pathology in MS has been investigated. This review focuses on the
      neuroimaging of gray matter pathology in MS, the effect of the accumulation of
      gray matter pathology on clinical and cognitive disability, and the effect of
      disease-modifying agents on various measures of gray matter damage. 

PMID- 23878738
TI  - Vascular Reactivity Concerning Orthosiphon stamineus Benth-Mediated
      Antihypertensive in Aortic Rings of Spontaneously Hypertensive Rats.
AB  - Orthosiphon stamineus Benth has been traditionally used to treat hypertension.
      The study aimed to investigate the vascular reactivity of water extract (WOS) and
      water : methanolic (1 : 1) extract (WMOS) of Orthosiphon stamineus Benth and AT1
      receptors blocker in the mechanisms of antihypertensive mediated by alpha 1
      adrenergic receptor and EDNO and PGI2 releases in the SHR aortic rings. SHR (230
      280 g) were divided into four groups: control, WOS, WMOS, and losartan. After
      being fed orally for 14 days, the aorta was harvested and subjected to PE (10(-9)
      to 10(-5) M) and ACh (10(-9) to 10(-5) M) with and without L-NAME (100 uM) and
      indomethacin (10 uM), respectively. WOS, WMOS, and losartan significantly reduced
      the contractile responses to PE intact suggesting the importance of endothelium
      in vasorelaxation. Losartan significantly enhanced the ACh-induced
      vasorelaxation. L-NAME significantly inhibited the ACh-induced relaxation in all
      groups. Indomethacin enhanced ACh-induced vasorelaxation in WMOS. Collectively,
      Orthosiphon stamineus leaves extract reduced vasoconstriction responses by the
      alteration of alpha 1-adrenergic and AT1 receptors activities. The involvement of
      EDNO releases was clearly observed in this plant. In WOS, PGI2 releases might not
      participate in the ACh-induced vasorelaxation. However, in WMOS, enhancement of
      vasorelaxation possibly due to continuous release of PGI2. 

PMID- 23878737
TI  - "Near miss" obstetric events and maternal deaths in a tertiary care hospital: an
      audit.
AB  - OBJECTIVES: (1) To determine the frequency of maternal near miss, maternal near
      miss incidence ratio (MNMR), maternal near miss to mortality ratio and mortality
      index. (2) To compare the nature of near miss events with that of maternal
      mortality. (3) To see the trend of near miss events. DESIGN: Audit. SETTING:
      Kasturba Hospital, Manipal University, Manipal, India. POPULATION: Near miss
      cases & maternal deaths. METHODS: Cases were defined based on WHO criteria 2009.
      MAIN OUTCOME MEASURES: Severe acute maternal morbidity and maternal deaths.
      RESULTS: There were 7390 deliveries and 131 "near miss" cases during the study
      period. The Maternal near miss incidence ratio was 17.8/1000 live births,
      maternal near miss to mortality ratio was 5.6 : 1, and mortality index was 14.9%.
      A total of 126 cases were referred, while 5 cases were booked at our hospital.
      Hemorrhage was the leading cause (44.2%), followed by hypertensive disorders
      (23.6%) and sepsis (16.3%). Maternal mortality ratio (MMR) was 313/100000 live
      births. CONCLUSION: Hemorrhage and hypertensive disorders are the leading causes
      of near miss events. New-onset viral infections have emerged as the leading cause
      of maternal mortality. As near miss analysis indicates the quality of health
      care, it is worth presenting in national indices.

PMID- 23878739
TI  - Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small
      biopsies and clinicopathological correlation.
AB  - Squamous cell carcinoma (SCC) is a common and important primary cutaneous
      malignancy. On skin biopsies, SCC is characterized by significant squamous cell
      atypia, abnormal keratinization, and invasive features. Diagnostic challenges may
      occasionally arise, especially in the setting of small punch biopsies or
      superficial shave biopsies, where only part of the lesion may be assessable by
      the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia,
      eccrine squamous syringometaplasia, inverted follicular keratosis, and
      keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma,
      melanoma, and metastatic carcinoma. The careful application of time-honored
      diagnostic criteria, close clinicopathological correlation and a selective
      request for a further, deeper, or wider biopsy remain the most useful strategies
      to clinch the correct diagnosis. This review aims to present the key differential
      diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to
      deal with diagnostically challenging cases. 

PMID- 23878740
TI  - Management of bleeding in extrahepatic portal venous obstruction.
AB  - Extrahepatic portal venous obstruction, although rare in the western world, is a
      common cause of major and life threatening upper gastrointestinal bleeding among
      the poor in developing countries. Patients have large spleens and stunted growth.
      The diagnosis is easily confirmed by Doppler ultrasonography. Endoscopy
      sclerotherapy is the best option for the control of acute variceal bleeding. For
      secondary prophylaxis of bleeding, the choice lies between repeated sclerotherapy
      and a portosystemic shunt. We believe that due consideration should be given to
      performing a splenectomy and a lienorenal shunt. Performed by experienced
      surgeons, it carries a low operative mortality of 1%, a rebleeding rate of about
      10%, removes the large spleen, reverses hypersplenism, and is not followed by
      portosystemic encephalopathy. Most importantly, it is a onetime procedure
      particularly suited to those who have little access to blood transfusion and
      sophisticated medical facilities. 

PMID- 23878741
TI  - Vacuum Assisted Closure Therapy versus Standard Wound Therapy for Open
      Musculoskeletal Injuries.
AB  - Background. This study was performed to evaluate the results of vacuum assisted
      wound therapy in patients with open musculoskeletal injuries. Study Design and
      Setting. Prospective, randomized, and interventional at tertiary care hospital,
      from 2011 to 2012. Materials and Methods. 30 patients of open musculoskeletal
      injuries underwent randomized trial of vacuum assisted closure therapy versus
      standard wound therapy around the upper limb and lower limb. Mean patient age was
      39 +/- 18 years (range, 18 to 76 years). Necrotic tissues were debrided before
      applying VAC therapy. Dressings were changed every 3 or 4 days. For standard
      wound therapy, debridement followed by daily dressings was done. Data Management
      and Statistical Analysis. The results obtained were subjected to statistical
      analysis. Results. The size of soft tissue defects reduced more than 5 mm to 25
      mm after VAC (mean decrease of 26.66%), whereas in standard wound therapy,
      reduction in wound size was less than 5 mm. A free flap was needed to cover
      exposed bone and tendon in one case in standard wound therapy group. No major
      complication occurred that was directly attributable to treatment. Conclusion.
      Vacuum assisted wound therapy was found to facilitate the rapid formation of
      healthy granulation tissue on open wounds in the upper limb and lower limb, thus
      to shorten healing time and minimize secondary soft tissue defect coverage
      procedures. 

PMID- 23878742
TI  - Assessment of Gingival Health Status among 5- and 12-Year-Old Children in Yemen:
      A Cross-Sectional Study.
AB  - Purpose. There are limited data about the gingival health status in Yemeni
      children. The aim, therefore, was to assess oral hygiene status and prevalence
      and severity of gingivitis among Yemeni preschool and school children. Materials
      and Methods. A total of 5396 children were included from 5 representative Yemeni
      governorates: Sana'a, Hajjah, Hodeida, Hadramaut, and Taiz. Five-year olds (1292)
      were recruited from private kindergartens while 12-year olds (4104) were selected
      from public primary schools. Gingival health status was assessed using the plaque
      index (PI), calculus index (CAI), and gingival index (GI) on the 6 Ramfjord
      teeth. The latter index was used to categorize gingivitis severity at the subject
      level. Data were analyzed using simple hypothesis testing, as well as ordinal
      regression. Results. The 12-year old children had significantly much higher mean
      PI, CAI, and GI (P < 0.001) with 78.6% presenting with gingivitis and 47.8% with
      moderate gingivitis. In contrast, the figures were 27.2% and 3.1% in the younger
      group (P < 0.001). There were significant variations according to gender, area of
      residence, and governorate. Regression analysis revealed that mean PI (OR = 35),
      mean CAI (OR = 7.7), male gender (OR = 1.6), living in rural areas (OR = 1.4),
      and being from Hajjah or Sana'a were independent risk factors of gingivitis
      severity in the older group. For the 5-year olds, the determinants were mean PI
      (OR = 122), male gender (OR = 1.4), and living in Sana'a or Taiz. Conclusions.
      Bad oral hygiene and moderate gingivitis are highly prevalent among Yemeni
      preschool and school children. Geographical location appeared as important
      independent risk factors of gingival inflammation. 

PMID- 23878743
TI  - Relationship between Conformation Traits and Lifetime Production Efficiency of
      Cows.
AB  - Analysis was made of the relationship between conformation traits and lifetime
      production efficiency of the cows that first calved in 2000 and represented the
      active population in the Pomorze and Kujawy regions of Poland. The CORR Pearson
      procedures of SAS package were used in the statistical calculations. It was found
      that there is a statistically significant relationship, weak or low on the
      Guilford scale, between conformation traits and lifetime production efficiency of
      the cows, which is slightly higher for milk yield than for longevity. The type
      and conformation traits appear to be more suitable than the detailed traits for
      predicting the lifetime production efficiency of cows. Lifetime performance was
      most strongly related to the overall score and udder score (r = 0.22), followed
      by the scores for type and conformation and legs and feet (r = 0.13), and
      detailed traits such as udder width and dairy character (r = 0.14). The highest
      positive effect on longevity was exerted by udder score and legs and feet (r =
      0.11) and among detailed traits by udder placement (r = 0.14) and fore udder
      attachment (r = 0.10). 

PMID- 23878744
TI  - The epidermal growth factor receptor increases cytokine production and cutaneous
      inflammation in response to ultraviolet irradiation.
AB  - The epidermal growth factor receptor (EGFR) is activated in cutaneous
      keratinocytes upon ultraviolet (UV) exposure and has been implicated in
      ultraviolet-(UV-)induced inflammation and skin tumorigenesis. Egfr mutant mice
      and EGFR inhibitors were used to investigate the hypothesis that EGFR activation
      augments inflammation following UV irradiation. Topical treatment of mouse skin
      with the EGFR inhibitor AG1478 before UV exposure suppressed UV-induced erythema,
      edema, mast cell infiltration, and neutrophil infiltration. Genetic ablation of
      Egfr and EGFR inhibition by AG1478 also suppressed the increase in the
      proinflammatory cytokines tumor necrosis factor alpha (TNF- alpha ), interleukin
      1 alpha , KC (murine IL-8), and cyclooxygenase-2 (COX-2) after UV exposure of
      cultured keratinocytes. Finally, genetic ablation of inhibition of EGFR in
      cultured keratinocytes decreased p38 activation after UV, while inhibition of p38
      kinase reduced COX-2 expression after UV. These data demonstrate that EGFR
      regulates multiple aspects of UV-induced inflammation and suggest activation of
      p38 kinase leading to increased COX-2 and cytokine expression as one mechanism
      through which it acts. 

PMID- 23878746
TI  - Quantifying gait impairment using an instrumented treadmill in people with
      multiple sclerosis.
AB  - Background and Objective. Treadmill gait analysis has been proposed as an
      attractive alternative for overground walking measuring systems. The purpose of
      this study was twofold: first to determine spatiotemporal parameters of treadmill
      gait in patients with multiple sclerosis (MS) and second to examine whether these
      parameters are associated with specific functional impairments in this cohort.
      Method. Eighty-seven relapsing-remitting patients diagnosed with MS, 50 women and
      37 men, aged 40.9 +/- 11.9 with an expanded disability status scale (EDSS) score
      of 2.7 +/- 1.6, participated in this study. Twenty-five apparently healthy
      subjects, 14 women and 11 men, aged 38.5 +/- 9.4, served as controls.
      Spatiotemporal gait parameters were obtained using the Zebris FDM-T Treadmill
      (Zebris Medical GmbH, Germany). People with MS demonstrated significantly shorter
      steps, extended stride time, wider base of support, longer step time, reduced
      single support phase, and a prolonged double support phase compared to the
      healthy controls. The EDSS score was significantly correlated with all
      spatiotemporal gait parameters. Conclusion. The instrumented treadmill may be an
      effective tool in assessing ambulation capabilities of people with MS. 

PMID- 23878745
TI  - Autoimmune thyroid disorders.
AB  - Purpose of Review. Studies have been published in the field of autoimmune thyroid
      diseases since January 2005. The review is organized into areas of etiology,
      autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell
      responses, and T-cell responses. Also it reviews the diagnosis and the
      relationship between autoimmune thyroid disease, neoplasm, and kidney disorders.
      Recent Findings. Autoimmune thyroid diseases have been reported in people living
      in different parts of the world including North America, Europe, Baalkans, Asia,
      Middle East, South America, and Africa though the reported figures do not fully
      reflect the number of people infected per year. Cases are unrecognized due to
      inaccurate diagnosis and hence are treated as other diseases. However, the most
      recent studies have shown that the human autoimmune thyroid diseases (AITDs)
      affect up to 5% of the general population and are seen mostly in women between 30
      and 50 years. Summary. Autoimmune thyroid disease is the result of a complex
      interaction between genetic and environmental factors. Overall, this review has
      expanded our understanding of the mechanism involved in pathogenesis of AITD and
      the relationship between autoimmune thyroid disease, neoplasm, and kidney
      disease. It has opened new lines of investigations that will ultimately result in
      a better clinical practice. 

PMID- 23878747
TI  - Incidental radiographic discovery of a screw in a primary molar: an unusual case
      report in a 6 year old child.
AB  - Dentists often find foreign bodies in the primary dentition of children who
      habitually place objects in their mouths. The objects are frequently embedded in
      exposures that result from carious or traumatic lesions or from endodontic
      procedures that have been left open for drainage. Such bodies are often detected
      on routine radiographs and, less frequently, during clinical examination. We
      report a case of a 6-year-old boy who had inadvertently embedded a screw in his
      mandibular right first primary molar and had forgotten about it until it became
      symptomatic. The screw was impacted in the exposed pulp chamber due to a large
      carious lesion in the affected molar. This case report considers the possible
      medical and dental consequences of placing foreign bodies in the mouth. 

PMID- 23878748
TI  - Peripheral ossifying fibroma.
AB  - Intraoral ossifying fibromas have been described in the literature since the late
      1940s. Peripheral ossifying fibroma (POF) is usually a fibroma of the gingival
      which shows areas of calcification or ossification. It is a nonneoplastic
      enlargement of gingiva. Due to its clinical and histopathological similarities,
      some POFs are believed to develop initially as a pyogenic granuloma that
      undergoes fibrous maturation and subsequent calcification. It has been suggested
      that POF represents a separate clinical entity rather than a transitional form of
      pyogenic granuloma or irritation fibroma. This paper describes a case report of a
      60-year-old female patient reported with growth on gingiva in the upper left
      front region of mouth three years ago. 

PMID- 23878749
TI  - Peritoneal tuberculosis in an immunocompetent, unknown risk patient.
AB  - A 36-year-old man with no significant past medical history presented with two
      month abdominal distention, night sweats, and weight loss of 15 Ib. He had no
      known exposure to tuberculosis. PPD test was negative prior to the hospital
      admission. Physical examination was notable for new onset ascites, but no
      superficial lymphadenopathy or stigmata of chronic liver disease was found. CT
      scan demonstrated enlarged mesenteric lymph nodes, and prominent retroperitoneal
      lymph nodes along with moderate ascites and omental infiltration. Diagnostic
      paracentesis yielded WBC of 295/mm(3), lymphocytic predominance (70%), and serum
      ascitic albumin gradient of 0.1, consistent with exudate. Both the ascitic
      culture and AFB smear were negative, and ascitic cytology revealed nonmalignant
      cells. Exploratory laparoscopy for excisional biopsy of mesenteric lymph nodes
      was performed. Pathologic findings revealed caseous granulomas with scattered
      multinucleated giant cells. Mesenteric lymph node tissue culture subsequently
      grew Mycobacterium tuberculosis complex and the diagnosis of peritoneal
      tuberculosis was confirmed. The patient was started on quadruple therapy. A
      couple of days after the antibiotics were started, the small bowel obstruction
      started to resolve with resumption of bowel movements and tolerance of oral
      intake. A week later, ascites stopped accumulating and fever was no longer noted.
      He has been well and continues to be under observation. 

PMID- 23878750
TI  - Ovarian hyperstimulation syndrome as an etiology of obstructive uropathy.
AB  - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of
      controlled ovarian hyperstimulation (COH) protocols performed in women undergoing
      assisted reproductive technologies. Overstimulation of the ovaries results in the
      overproduction of vasoactive cytokines and mediators by the ovaries, thereby
      causing a generalized capillary leak and acute shift of protein-rich fluid from
      the intravascular compartment into the third space. This may lead to the
      development of ascites, pleural effusions, pericardial effusion, anasarca,
      intravascular volume depletion, hemoconcentration, oliguria, hypoalbuminemia and
      hypoproteinemia, electrolyte imbalances, acute renal failure, abdominal
      compartment syndrome, thromboembolic events, and adult respiratory distress
      syndrome. The only effective treatment available is prevention of the syndrome
      from developing by individualizing the stimulation protocol, especially in high
      risk patients. Once the syndrome develops, the management is mainly supportive.
      Oliguria and some degree of acute renal failure commonly develop in patients with
      moderate to severe OHSS and are usually due to prerenal causes. Acute renal
      failure (ARF) secondary to obstructive uropathy is rare. Here we report a case of
      severe, life-threatening OHSS resulting in ARF secondary to obstructive uropathy.

PMID- 23878751
TI  - Primary small cell carcinoma of the vagina.
AB  - The primary small cell carcinoma of the vagina is rare, and it is a highly
      aggressive malignancy with no consensus regarding the treatment of this tumor.
      The survival rate for patients treated in the early stages is around two years.
      We related the case report of a patient of 41 years with a vegetative and
      necrotic lesion in left vaginal wall, in middle and upper third, and involvement
      of parametrium in its proximal third and medium third. A biopsy showed a small
      cell undifferentiated carcinoma composed of epithelial cells with round nuclei,
      oval or elongated, hyperchromatic nuclei, with little distinct nucleoli, and
      scarce cytoplasm. Immunohistochemistry showed positivity for AE1/AE3, CD57, and
      chromogranin A. The patient received 6 cycles of chemotherapy with cisplatin and
      etoposide and radiotherapy, achieving complete response, with complete regression
      of the lesion. The patient had no sign of tumor recurrence and locoregional or
      distant metastases after 5 months of followup. 

PMID- 23878752
TI  - Poorly differentiated ovarian sertoli-leydig cell tumor in a 16-year-old single
      woman: a case report and literature review.
AB  - Sertoli-Leydig cell tumor (SLCT) of ovary is an exceedingly unusual neoplasm that
      belongs to a group of sex cord-stromal tumors of ovary and accounts for less than
      0.5% of all primary ovarian neoplasms. Very few case reports have been documented
      in the literature so far. Herein, we report a case of primary poorly
      differentiated ovarian Sertoli-Leydig cell tumor (SLCT) involving the left ovary
      in a 16-year-old single woman who presented with a 3-month history of a
      pelviabdominal mass, acne, hirsutism, and menstrual irregularities. In addition,
      a literature review on ovarian SLCTs is provided. 

PMID- 23878753
TI  - Metastases of renal cell carcinoma to the thyroid gland with synchronous benign
      and malignant follicular cell-derived neoplasms.
AB  - Clear cell renal cell carcinoma (CCRCC) is the most common origin for metastasis
      in the thyroid. A 51-year-old woman was referred to our hospital for a subcarinal
      lesion. Ten years before, the patient had undergone a nephrectomy for CCRCC.
      Whole-body fluorodeoxyglucose positron emission tomography revealed elevated
      values in the thyroid gland, while the mediastinum was normal. An endoscopic
      ultrasonography-guided fine-needle aspiration biopsy of the mediastinal mass was
      consistent with CCRCC, and this was confirmed after resection. The thyroidectomy
      specimen also revealed lymphocytic thyroiditis, nodular hyperplasia, one
      follicular adenoma, two papillary microcarcinomas, and six foci of metastatic
      CCRCC involving both thyroid lobes. Curiously two of the six metastatic foci were
      located inside two adenomatoid nodules (tumor-in-tumor). The metastatic cells
      were positive for cytokeratins, CD10, epidermal growth factor receptor, and
      vascular endothelial growth factor receptor 2. No BRAF gene mutations were found
      in any of the primary and metastatic lesions. The patient was treated with
      sunitinib and finally died due to CCRCC distant metastases 6 years after the
      thyroidectomy. In CCRCC patients, a particularly prolonged survival rate may be
      achieved with the appropriate therapy, in contrast to the ominous prognosis
      typically found in patients with thyroid metastases from other origins. 

PMID- 23878754
TI  - Total hip arthroplasty after treatment of pseudojoint infection in a patient with
      a highly dislocated hip.
AB  - Infection at the pseudoacetabulum in a patient with a high hip dislocation has
      not been reported previously in the English literature. We report a case of total
      hip arthroplasty in a 28-year-old female who presented to us with hip pain
      following debridement of the infected pseudojoint in a case of neglected
      developmental dysplasia of the hip. The infection was treated with thorough
      debridement and drainage. However, even after achieving complete infection
      control, this patient complained of disabling right hip joint pain. Total hip
      arthroplasty with subtrochanteric osteotomy was performed to relieve the pain and
      improve gait. After surgery, the patient's symptoms were relieved. We consider
      that in this case of acute pseudojoint infection simple arthrotomy and
      debridement combined with irrigation and drainage provide effective treatment.
      But muscle weakness and more increased joint laxity can cause hip pain even after
      infection control. So total hip arthroplasty is likely to be necessary after the
      infection has been controlled in a patient with a highly dislocated hip. 

PMID- 23878755
TI  - Customized tracheostomy cannula as a therapeutic adjunct in tracheal stenosis.
AB  - Tracheotomy is often successfully used to manage tracheal stenosis, as a
      temporizing measure prior to definitive treatment or a long-term remedy. In some
      patients, where a sizeable portion trachea is stenotic, the fixed arm of an
      ordinary tracheotomy tube may not be of sufficient length to satisfactorily
      maintain the distal tracheal lumen, and commercially available adjustable tubes
      may not be at hand in certain clinical settings. Herein, we describe a simple
      method of constructing a temporary tracheotomy tube with an adjustable distal
      arm, allowing custom fit at the patient bedside. 

PMID- 23878756
TI  - An unusual cause of small bowel obstruction in a child: ingested rhubarb.
AB  - Small bowel obstruction is rarely caused by bezoars concretions formed from
      undigested foreign material in the gastrointestinal tract. An important cause of
      bezoars is phytobezoars, formed from vegetables or fruits. A four-year-old boy
      presented to our emergency department with symptoms of acute intestinal
      obstruction. Upright plain abdominal radiography revealed multiple air fluid
      levels. Ultrasound showed no abnormalities, and because of worsening symptoms
      computed tomography of abdomen was performed. It showed intraluminal obstruction
      of the terminal ileum. Exploratory laparotomy revealed a phytobezoar consisting
      of undigested rhubarb. The mass was milked through the large bowel and out the
      anus. Although rare in humans, bezoars are a well-documented cause of small bowel
      obstruction and should be considered when intraluminal bowel obstruction occurs.
      Bezoars causing small bowel obstruction may require surgical treatment. 

PMID- 23878757
TI  - Usefulness of infrared thermal imaging camera for screening of postoperative
      surgical site infection after the nuss procedure.
AB  - Introduction and Objective. The Nuss procedure is widely used in the treatment of
      pectus excavatum worldwide. Postoperative pectus bar infection is one of the most
      serious complications associated with this procedure. Therefore, early detection
      of signs of implant infection is very important. However, this is difficult, and
      effective methods have yet to be established. Methods. We use a handheld infrared
      thermal imaging camera to screen patients for postoperative infection following
      the Nuss procedure. Here, we report a 28-year-old man with recurrent
      postoperative (Ravitch procedure) pectus excavatum. Results. Infrared
      thermography camera clearly indicated slight cellulitis in the right chest.
      Conclusion. Our technique may assist in preventing postoperative bar infection
      and removal caused by severe bar infection. Furthermore, this camera is
      potentially suitable for many situations in infection monitoring following
      subcutaneous implant surgery. 

PMID- 23878758
TI  - Rare case of renal cell carcinoma with mandibular swelling as primary
      presentation.
AB  - Introduction. Renal cell carcinoma accounts for approximately 3% of adult
      malignancies and 90-95% of neoplasms arising from the kidney. This disease is
      characterized by a lack of early warning signs, diverse clinical manifestations,
      and resistance to radiation and chemotherapy. Approximately one-third of patients
      with renal cell carcinoma have metastatic disease at initial presentation.
      Fifteen percent of patients with renal cell carcinoma are said to present with
      metastases in the head and neck region. Most of the metastases from RCC to the
      head and neck involve the thyroid gland. The head and neck are unusual sites for
      metastases, but skin, skeletal muscle, thyroid gland, nasal cavity and paranasal
      sinus metastases have been reported. Case Report. The following report describes
      a rare case where the patient presented with mandibular swelling of short
      duration as the primary complaint without any symptom or sign pertaining to
      urinary tract and was found to have renal cell carcinoma on further workup.
      Conclusion. Metastatic renal cell carcinoma is a diagnostic dilemma especially
      when there is no pointer historically towards renal cell carcinoma as was in our
      case. An unusual vascular osteolytic lesion in head and neck in a middle-aged
      person should be dealt with high index of suspicion with renal cell carcinoma at
      the back of the mind. 

PMID- 23878759
TI  - Serum dickkopf-1 level in postmenopausal females: correlation with bone mineral
      density and serum biochemical markers.
AB  - Objective. To assess serum level of Dickkopf-1 in postmenopausal females and its
      correlation with bone mineral density and serum biochemical markers. Methods.
      Bone densitometry, serum Dickkopf-1, calcium, phosphorus, and alkaline
      phosphatase were done in sixty postmenopausal females. Patients were divided
      according to T score into osteoporosis (group I), osteopenia (group II), and
      normal bone mineral density that served as controls. Results. There was highly
      significant increase in serum Dickkopf-1 levels in postmenopausal females with
      abnormal T score versus controls (P < 0.001). Serum DKK-1 levels correlated
      negatively with both lumbar T score (r = -0.69, P < 0.001) and femur T score (r =
      -0.64, P < 0.001) and correlated positively with duration of menopause (r = 0.61,
      P < 0.001), while there was no significant correlation between serum levels of
      either calcium, phosphorus or alkaline phosphatase, and both serum Dickkopf-1
      levels and the level of bone mineral density (P > 0.05). Conclusion.
      Postmenopausal females may suffer from osteoporosis as evidenced by bone
      densitometry. Postmenopausal women with significantly increased serum Dickkopf-1
      had more significant osteoporosis. Prolonged duration of menopause and increased
      serum Dickkopf-1 are important risk factors for the development and severity of
      osteoporosis. 

PMID- 23878761
TI  - Simultaneous Determination of Gallic Acid, Ellagic Acid, and Eugenol in Syzygium
      aromaticum and Verification of Chemical Antagonistic Effect by the Combination
      with Curcuma aromatica Using Regression Analysis.
AB  - This study was designed to perform simultaneous determination of three reference
      compounds in Syzygium aromaticum (SA), gallic acid, ellagic acid, and eugenol,
      and to investigate the chemical antagonistic effect when combining Curcuma
      aromatica (CA) with SA, based on chromatographic analysis. The values of LODs and
      LOQs were 0.01-0.11  MU g/mL and 0.03-0.36  MU g/mL, respectively. The intraday
      and interday precisions were <3.0 of RSD values, and the recovery was in the
      range of 92.19-103.24%, with RSD values <3.0%. Repeatability and stability were
      0.38-0.73% and 0.49-2.24%, respectively. Compared with the content of reference
      and relative peaks in SA and SA combined with CA (SAC), the amounts of gallic
      acid and eugenol were increased, while that of ellagic acid was decreased in SAC
      (compared with SA), and most of peak areas in SA were reduced in SAC. Regression
      analysis of the relative peak areas between SA and SAC showed r (2) values >0.87,
      indicating a linear relationship between SA and SAC. These results demonstrate
      that the components contained in CA could affect the extraction of components of
      SA mainly in a decreasing manner. The antagonistic effect of CA on SA was
      verified by chemical analysis. 

PMID- 23878762
TI  - A water marker monitored by satellites to predict seasonal endemic cholera.
AB  - The ability to predict an occurrence of cholera, a water-related disease, offers
      a significant public health advantage. Satellite based estimates of chlorophyll,
      a surrogate for plankton abundance, have been linked to cholera incidence.
      However, cholera bacteria can survive under a variety of coastal ecological
      conditions, thus constraining the predictive ability of the chlorophyll, since it
      provides only an estimate of greenness of seawater. Here, a new remote sensing
      based index is proposed: Satellite Water Marker (SWM), which estimates condition
      of coastal water, based on observed variability in the difference between blue
      (412 nm) and green (555 nm) wavelengths that can be related to seasonal cholera
      incidence. The index is bounded between physically separable wavelengths for
      relatively clear (blue) and turbid (green) water. Using SWM, prediction of
      cholera with reasonable accuracy, with at least two month in advance, can
      potentially be achieved in the endemic coastal regions.

PMID- 23878760
TI  - Aneurysmal subarachnoid hemorrhage models: do they need a fix?
AB  - The discovery of tissue plasminogen activator to treat acute stroke is a success
      story of research on preventing brain injury following transient cerebral
      ischemia (TGI). That this discovery depended upon development of embolic animal
      model reiterates that proper stroke modeling is the key to develop new
      treatments. In contrast to TGI, despite extensive research, prevention or
      treatment of brain injury following aneurysmal subarachnoid hemorrhage (aSAH) has
      not been achieved. A lack of adequate aSAH disease model may have contributed to
      this failure. TGI is an important component of aSAH and shares mechanism of
      injury with it. We hypothesized that modifying aSAH model using experience
      acquired from TGI modeling may facilitate development of treatment for aSAH and
      its complications. This review focuses on similarities and dissimilarities
      between TGI and aSAH, discusses the existing TGI and aSAH animal models, and
      presents a modified aSAH model which effectively mimics the disease and has a
      potential of becoming a better resource for studying the brain injury mechanisms
      and developing a treatment. 

PMID- 23878763
TI  - Comparison of operating field sterility in open versus minimally invasive
      microdiscectomies of the lumbar spine.
AB  - BACKGROUND: Postoperative wound infection is a preventable risk that can lead to
      significant adverse outcomes and increased cost of care. Minimally invasive
      surgeries (MIS) have been found to have lower rates of postoperative infection
      compared with the traditional approach. To assess if the reported difference is
      related to intraoperative contamination or to other factors, we assessed the
      surgical field for sterility. METHODS: We compared 10 MIS versus 10 traditional
      microdiscectomies. Swabs of the operating field were obtained before and after
      the procedure from multiple sites in the operating room. Positive and negative
      controls were taken of the skin immediately before and after preparation of the
      incision site. All swabs were plated out on Columbia blood agar plates and grown
      for 48 hours. Colony counting was performed to determine growth. RESULTS: There
      was no statistically significant difference in the colony counts of swab sites in
      traditional microdiscectomies compared with MIS microdiscectomies. There was no
      significant contamination of the operating field using either approach.
      CONCLUSIONS: In this prospective study, we found that there was no significant
      difference in bacterial counts in swabs of operative sites in either traditional
      or MIS microdiscectomies, suggesting that the decreased rate of postoperative
      infection in the reported literature for MIS cases may be related to other
      factors, such as patient selection and/or postoperative care.

PMID- 23878764
TI  - When does a spinal surgeon need a plastic surgeon?

PMID- 23878765
TI  - Clinical approach to fever in the neurosurgical intensive care unit: Focus on
      drug fever.
AB  - As fever is one of the cardinal signs of infection, the presence of fever in a
      patient in the neurosurgical intensive care unit (NSICU) raises the question of
      whether it is infectious in etiology. Infectious and noninfectious causes of
      fever in the NSICU may be determined based upon assessment of clinical signs and
      symptoms, the degree of temperature elevation, the relationship of the pulse to
      the fever (e.g., an infectious process resulting in hyperpyrexia and
      bradycardia), and when the fever occurs (e.g., related to the length of stay in
      the NSICU). There are many noninfectious disorders which contribute to
      temperatures >102 degrees F in the NSICU; these include drug fevers, deep vein
      thrombosis, phlebitis/pulmonary embolism, acute myocardial infarction,
      atelectasis, dehydration, acute gout flare, malignancy, acute pancreatitis,
      transfusion associated hepatitis, and hemorrhage. Infectious rather than
      noninfectious disorders, however, are more typically associated with high-grade
      fevers (>102 degrees F.) in the NSICU, and nosocomial pneumonia, (synonymous with
      ventilator-associated pneumonia [VAP]), is the leading culprit, followed by
      nosocomial infections and Clostridium difficile. 

PMID- 23878766
TI  - The role of magnetic resonance imaging and positron emission tomography-computed
      tomography combined in differentiating benign from malignant lesions contributing
      to vertebral compression fractures.
AB  - BACKGROUND: Obtaining tissue confirmation of the underlying pathology is the gold
      standard for establishing the etiology of nontraumatic vertebral compression
      fractures. However, newer investigative modalities such as the magnetic resonance
      imaging (MRI) and positron emission tomography-computed tomography (PET-CT)
      combined potentially offer the ability to distinguish between benign and
      malignant lesions, thereby circumventing the need for invasive tissue
      diagnostic/biopsy procedures. METHODS: Twenty-four patients with nontraumatic,
      spontaneous vertebral compression fractures were prospectively studied. After
      clinical evaluation, all patients underwent MRI (with/without contrast) focusing
      on the spinal lesion, followed by whole-body PET-CT. This was followed by fine
      needle aspiration cytology (FNAC) of the lesion to confirm the diagnosis. The
      sensitivity and specificity of MRI and PET-CT studies were calculated for benign
      vs. malignant lesions. RESULTS: The sensitivity/specificity of MRI for benign
      lesions were 78.57%/90%, while the sensitivity/specificity values of PET-CT for
      benign disease were 92.8%/90% respectively. Alternatively, the
      sensitivity/specificity of MRI for malignant lesions were 90%/78.57%, while the
      sensitivity/specificity of PET-CT for malignant disease were 90%/92.8%,
      respectively. Furthermore, the sensitivity for diagnosing malignant lesions
      utilizing both studies together was 100%, but the algorithm was not specific.
      Additionally, the specificity for MRI and PET-CT combined was 100% for benign
      lesions. PET-CT also helped in monitoring responses to empirical antitubercular
      treatment (ATT) therapy. Of interest, FNAC was inconclusive in four cases in
      which PET-CT findings helped further in either obtaining a tissue diagnosis from
      another location or institution of empirical therapy in suspected cases of
      tuberculosis. CONCLUSIONS: The specificity for MRI and PET-CT combined was 100%
      for benign lesions. Unfortunately, the specificity for MRI and PET-CT combined
      was not 100% for malignant vertebral lesions, though it was sensitive. The PET-CT
      scan was an extremely useful tool when FNAC from the affected site proved
      inconclusive. It gave additional information regarding the overall extent of
      disease, while identifying other locations amenable to FNAC. Furthermore, in
      countries where tuberculosis is endemic, the empirical response to ATT therapy
      could be monitored utilizing PET-CT.

PMID- 23878767
TI  - Medicolegal corner: Quadriplegia following chiropractic manipulation.
AB  - A 45 year old male with multiple comorbidities presented to his internist with a
      2 week history of right sided neck pain and tenderness, accompanied by tingling
      in the hand. The internists' neurological examination was normal, except for
      decreased range of motion of the right arm. He referred the patient to a
      chiropractor; he performed plain X rays which revealed mild spasm, but never
      ordered a magnetic resonance imaging study. The chiropractor manipulated the
      patient's neck on two successive days. By the morning of the third visit, the
      patient reported extreme pain and difficulty walking. Without performing a new
      neurological examination or obtaining an MR scan, the chiropractor again
      manipulated the patient's neck. He immediately became quadriplegic. Despite
      undergoing an emergency C5 C6 anterior cervical diskectomy/fusion to address a
      massive disc found on the MR scan (CT was negative), the patient remained
      quadriplegic (e.g., C4 sensory, C6 motor levels). A major point of negligence in
      this case was the failure of both the referring internist and chiropractor to
      order an MR of the cervical spine prior to the chiropractic manipulation. The
      internist claimed that there was no known report of permanent quadriplegia
      resulting from neck manipulation in any medical journal, article or book, or in
      any literature of any kind or on the internet and that the risk of this injury
      must be vanishingly small given the large numbers of manipulations performed
      annually. The total amount of the verdict was $14,596,000.00 the internist's
      liability was 5% ($759,181.65). 

PMID- 23878768
TI  - "When the pain won't wane it's mainly in the brain".
AB  - Chronic pain syndromes either have no underlying organic explanation, or include
      patients whose chronic pain complaints (without focal deficits or significant
      radiographic findings) were not alleviated by surgery (in 80% of cases). Patients
      with chronic pain typically "turn off" members of the medical community; they are
      often "written off" as malingerers or psychiatric cases. The Minnesota
      Multiphasic Personality Inventory often shows elevations on the hysteria and
      hypochondriasis scales; together these constitute somatization defined as
      patients converting emotional distress into bodily complaints. Depression,
      anxiety, and borderline personality disorders are also often encountered.
      Secondary gain also plays a critical role in patients with chronic pain syndromes
      (e.g., includes avoiding onerous tasks/work, or rewards opioid-seeking
      behaviors). Tertiary gain pertains to the physicians' financial rewards for
      administering ineffective and repeated treatment of these patients, while
      validating for the patient that there is truly something organically wrong with
      them. Self-mutilation (part of Munchausen Syndrome/Fictitious Disorders) also
      brings these chronic pain patients to the attention of the medical community.
      They are also often involved in the legal system (e.g., workmen's compensation or
      tort action) that in the United States, unfortunately financially rewards "pain
      and suffering." The main purpose of this commentary is to reeducate spinal
      surgeons about the pitfalls of operating on patients with chronic pain syndromes
      in the absence of significant neurological deficits or radiographic findings, as
      such "last ditch surgery" invariably fails. 

PMID- 23878769
TI  - Complications due to the use of BMP/INFUSE in spine surgery: The evidence
      continues to mount.
AB  - Increasingly, adverse events (AE) attributed to utilizing BMP/INFUSE (Bone
      Morphogenetic Protein, Medtronic, Memphis, TN, USA) "off-label" in spine surgery
      are being reported. In 2008, the Food and Drug Administration (FDA) issued a
      warning that in anterior cervical spine surgery, the "off-label" use of
      BMP/INFUSE contributed to marked dysphagia, hematoma, seroma, swelling, and/or
      the need for intubation/tracheostomy. Subsequent studies have cited the following
      AE; heterotopic ossification (HO), osteolysis, infection, arachnoiditis,
      increased neurological deficits, retrograde ejaculation, and cancer. Furthermore,
      in 2011, Carragee et al. noted that 13 of the original industry-sponsored
      BMP/INFUSE spinal surgery studies failed to acknowledge multiple AE.
      Additionally, in 2012, Comer et al. observed that the frequency of retrograde
      ejaculation reported for BMP/INFUSE used "on-label" to perform Anterior Lumbar
      Interbody Fusion/Lumbar Tapered Fusion-Cage Device (ALIF/LT-Cage) was also
      largely "under-reported." To summarize, there is mounting evidence in the spinal
      literature that utilizing BMP/INFUSE in spinal fusions contributes to major
      perioperative and postoperative morbidity. 

PMID- 23878770
TI  - Imaging in the diagnosis of juvenile nasopharyngeal angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma (JNA) is a rare, benign, highly vascular,
      and locally aggressive tumor that predominantly occurs in adolescent males.
      Usually, the presenting symptom is a painless nasal obstruction or epistaxis;
      however, other symptoms may develop depending on the size and extent of the tumor
      mass. Owing to the vascularity of the tumor, incisional biopsy is not attempted.
      The diagnosis is dependent on multiplanar imaging modalities like Computed
      Tomography (CT), Magnetic Resonance Imaging (MRI), and Angiography. These imaging
      modalities help in assessing the tumor mass, pre-operative embolization of the
      feeder vessel, and treatment planning. Usually, patients with JNA are diagnosed
      by otorhinolaryngologists, but here, we present a rare case of JNA reporting to
      the dental hospital due to a tender palatal swelling. 

PMID- 23878771
TI  - Non-syndromic non-familial agenesis of major salivary glands: a report of two
      cases with review of literature.
AB  - Agenesis of the major salivary glands is a rare and unusual condition, with only
      a few cases documented in the literature. The anomaly can be total or partial,
      unilateral or bilateral, and involve the parotid, submandibular, and sublingual
      glands. The resultant xerostomia leads to extensive dental demineralization. The
      authors report two cases with decreased saliva volume, impaired dental condition
      with extensive loss of tooth structure, and an astonishing pattern of dental
      destruction most notable on the facial and lingual surfaces of incisors and
      canines that can be best described as "chipping." After detailed review of
      patient history, clinical examination, ultrasonography, contrast enhanced
      computed tomography, and magnetic resonance imaging a diagnosis of congenital
      absence of major salivary glands in both the patients was made. Dentists should
      be aware that salivary gland aplasia is an uncommon cause of dental
      deterioration. It may manifest itself not by extensive caries but as dental
      chipping effect. Early recognition and a therapeutic strategy can prevent further
      dental damage. 

PMID- 23878772
TI  - Salivary Duct Cyst: Histo-pathologic Correlation.
AB  - Non-neoplastic cysts of the salivary glands are uncommon and represent 2-5% of
      all salivary gland lesions. They are mainly mucoceles or salivary duct cysts.
      Unlike a mucocele, which is surrounded by granulation tissue, the salivary duct
      cyst is lined by epithelium. Salivary duct cysts are more common in the oral
      minor salivary glands and rarely occur in the major salivary glands, show a
      marked predilection for the superficial lobe of the parotid, and represent 10% of
      all salivary gland cysts. Neoplastic differentiation of the lining of the
      salivary duct cyst has been reported. We report a case of a salivary duct cyst of
      the left parotid gland, with a review of radiographic and histopathologic
      features. 

PMID- 23878773
TI  - Basal cell adenocarcinoma of the minor salivary glands involving palate and
      maxillary sinus.
AB  - Basal cell adenocarcinoma (BCAC) is a rare neoplasm accounting for only 2.9% of
      all salivary gland neoplasms. BCAC involving palatal minor salivary glands are
      exceedingly rare, and only 10 cases have been reported in the literature. The
      treatment of choice is surgical excision. Here, we report a case of a 55-year-old
      male patient with massive BCAC of palatal minor salivary gland extending into the
      maxillary sinus. This is the first case of BCAC treated by radiotherapy followed
      by chemotherapy. A follow-up check conducted after 14-months showed good
      prognosis. 

PMID- 23878774
TI  - Trochanteric area pain, the result of a quartet of bursal inflammation.
AB  - Bursitis is quite responsive to therapeutic intervention, once the afflicted area
      is accurately identified. This is especially notable for some hip complaints.
      Patients' use of the term "hip" can relate to anything from the low back to groin
      to lateral thigh pain. Trochanteric area surface localization of "hip" pain may
      afford an opportunity for immediate cure. Effectiveness of therapeutic
      intervention is predicated upon injection of not one or two, but all four peri
      trochanteric bursa with a depot (minimally water-soluble) corticosteroid. The
      term trochanteric bursitis suggests that the inflammation is more focal than what
      is clinically observed. While easier to express, perhaps it is time to refer to
      inflammation in this area, naming all four affected bursae. 

PMID- 23878775
TI  - Mechanical solution for a mechanical problem: Tennis elbow.
AB  - Lateral epicondylitis is a relatively common clinical problem, easily recognized
      on palpation of the lateral protuberance on the elbow. Despite the "itis" suffix,
      it is not an inflammatory process. Therapeutic approaches with topical non
      steroidal anti-inflammatory drugs, corticosteroids and anesthetics have limited
      benefit, as would be expected if inflammation is not involved. Other approaches
      have included provision of healing cytokines from blood products or stem cells,
      based on the recognition that this repetitive effort-derived disorder represents
      injury. Noting calcification/ossification of tendon attachments to the lateral
      epicondyle (enthesitis), dry needling, radiofrequency, shock wave treatments and
      surgical approaches have also been pursued. Physiologic approaches, including
      manipulation, therapeutic ultrasound, phonophoresis, iontophoresis, acupuncture
      and exposure of the area to low level laser light, has also had limited success.
      This contrasts with the benefit of a simple mechanical intervention, reducing the
      stress on the attachment area. This is based on displacement of the stress by use
      of a thin (3/4-1 inch) band applied just distal to the epicondyle. Thin bands are
      required, as thick bands (e.g., 2-3 inch wide) simply reduce muscle strength,
      without significantly reducing stress. This approach appears to be associated
      with a failure rate less than 1%, assuming the afflicted individual modifies the
      activity that repeatedly stresses the epicondylar attachments. 

PMID- 23878776
TI  - Use of intercostal nerves for different target neurotization in brachial plexus
      reconstruction.
AB  - Intercostal nerve transfer is a valuable procedure in devastating plexopathies.
      Intercostal nerves are a very good choice for elbow flexion or extension and
      shoulder abduction when the intraplexus donor nerves are not available. The best
      results are obtained in obstetric brachial plexus palsy patients, when direct
      nerve transfer is performed within six months from the injury. Unlike the adult
      posttraumatic patients after median and ulnar nerve neurotization with
      intercostal nerves, almost all obstetric brachial plexus palsy patients achieve
      protective sensation in the hand and some of them achieve active wrist and finger
      flexion. Use in combination with proper muscles, intercostal nerve transfer can
      yield adequate power to the paretic upper limb. Reinnervation of native muscles
      (i.e., latissimus dorsi) should always be sought as they can successfully be
      transferred later on for further functional restoration. 

PMID- 23878777
TI  - Cervical adjacent segment pathology following fusion: Is it due to fusion?
AB  - Adjacent segment pathology affects 25% of patients within ten years of anterior
      cervical diskectomy and fusion (ACDF). Laboratory studies demonstrate fused
      segments increase adjacent level stress including elevated intradiscal pressure
      and increased range of motion. Radiographic adjacent segment pathology (RASP) has
      been associated to ACDF in multiple statistically significant studies. Randomized
      controlled trials (RCTs) comparing anterior cervical discectomy and arthroplasty
      (ACDA) and ACDF have confirmed ACDF accelerates RASP. The question of greatest
      clinical interest is whether ACDA, artificial disc surgery, results in fewer
      adjacent level surgeries than ACDF. Current RCT follow up results reveal only non
      statistically significant trends favoring ACDA yet the post operative periods are
      only two to four years. Statistically significant increased RASP in ACDF patients
      however is already documented. The RCT patients' average ages are in the mid
      forties with an expected longevity of up to forty more years. Early statistically
      significant increased RASP in the ACDF patients supports our prediction that
      given sufficient follow up of ten or more years, fusion will lead to
      statistically significant higher rate of adjacent level surgery compared to
      artificial disc surgery. 

PMID- 23878778
TI  - Orthopaedic perspective on bone metastasis.
AB  - The incidence of cancer is increasing worldwide, with the advent of a myriad of
      new treatment options, so is the overall survival of these patients. However,
      from an orthopaedic perspective, there comes the challenge of treating more
      patients with a variety of metastatic bone lesions. The consequences of such
      lesions can be significant to the patient, from pain and abnormal blood results,
      including hypercalcemia, to pathological fracture. Given the multiple options
      available, the treatment of bone metastasis should be based on a patient-by
      patient manner, as is the case with primary bone lesions. It is imperative, given
      the various lesion types and locations, treatment of bone metastasis should be
      performed in an individualised manner. We should consider the nature of the
      lesion, the effect of treatment on the patient and the overall outcome of our
      decisions. The dissemination of primary lesions to distant sites is a complex
      pathway involving numerous cytokines within the tumour itself and the surrounding
      microenvironment. To date, it is not fully understood and we still base a large
      section of our knowledge on Pagets historic "seed and soil" theory. As we gain
      further understanding of this pathway it will allow us develop more medical based
      treatments. The treatment of primary cancers has long been provided in a multi
      disciplinary setting to achieve the best patient outcomes. This should also be
      true for the treatment of bone metastases. Orthopaedic surgeons should be
      involved in the multidisciplinary treatment of such patients given that there are
      a variety of both surgical fixation methods and non-operative methods at our
      disposal. 

PMID- 23878779
TI  - Errors in visual estimation of flexion contractures during total knee
      arthroplasty.
AB  - AIM: To quantify and reduce the errors in visual estimation of knee flexion
      contractures during total knee arthroplasty (TKA). METHODS: This study was
      divided into two parts: Quantification of error and reduction of error. To
      quantify error, 3 orthopedic surgeons visually estimated preoperative knee
      flexion contractures from lateral digital images of 23 patients prior to and
      after surgical draping. A repeated-measure analysis of variance was used to
      compare the estimated angles prior to and following the placement of the surgical
      drapes with the true knee angle measured with a long-arm goniometer. In an effort
      to reduce the error of visual estimation, a dual set of inclinometers was
      developed to improve intra-operative measurement of knee flexion contracture
      during TKA. A single surgeon performed 6 knee extension measurements with the
      device during 146 consecutive TKA cases. Three measurements were taken with the
      desired tibial liner trial thickness, and 3 were taken with a trial that was 2 mm
      thicker. An intraclass correlation coefficient (ICC) was calculated to assess the
      test-retest reliability for the 3 measurements taken with the desired liner
      thickness, and a paired t test was used to determine if the knee extension
      measurements differed when a thicker tibial trial liner was placed. RESULTS: The
      surgeons significantly overestimated flexion contractures in 23 TKAs prior to
      draping and significantly underestimated the contractures after draping (actual
      knee angle = 6.1 degrees  +/- 6.4 degrees , pre-drape estimate = 6.9 degrees  +/-
      6.8 degrees , post-drape estimate = 4.3 degrees  +/- 6.1 degrees , P = 0.003).
      Following the development and application of the measurement devices, the
      measurements were highly reliable (ICC = 0.98), and the device indicated that 2.7
      degrees  +/- 2.2 degrees  of knee extension was lost with the insertion of a 2 mm
      thicker tibial liner. The device failed to detect a difference in knee extension
      angle with the insertion of the 2 mm thicker liner in 9/146 cases (6.2%).
      CONCLUSION: We determined the amount of error associated with visual estimation
      of knee flexion contractures, and developed a simple, reliable device and method
      to improve feedback related to sagittal alignment during TKA.

PMID- 23878780
TI  - Biomechanical characteristics of bone in streptozotocin-induced diabetic rats: An
      in-vivo randomized controlled experimental study.
AB  - AIM: To investigate the in vivo effects of type I diabetes on the mechanical
      strength of tibial bone in a rodent model. METHODS: The biomechanical effect of
      diabetes on the structural integrity of the tibia in streptozotocin induced
      diabetic Wistar rats was analysed. Induction of diabetes was achieved by an intra
      peritoneal injection and confirmed by measuring serial blood glucose levels (>
      150 mg/dL). After 8 wk the tibiae were harvested and compared to a control group.
      Biomechanical analysis of harvested tibiae was performed using a three-point
      bending technique on a servo hydraulic MTS 858 MiniBionix frame. Maximum force
      applied to failure (N), stiffness (N * mm) and energy absorbed (N/mm) were
      recorded and plotted on load displacement curves. A displacement control loading
      mode of 1 mm/min was selected to simulate quasi-static loading conditions.
      Measurements from load-displacement curves were directly compared between groups.
      RESULTS: Fourteen streptozotocin induced diabetic Wistar rats were compared
      against nineteen non-diabetic controls. An average increase of 155.2 g in body
      weight was observed in the control group compared with only 5 g in the diabetic
      group during the experimental study period. Levels of blood glucose increased to
      440.25 mg/dL in the diabetic group compared to 116.62 mg/dL in the control
      group.The biomechanical results demonstrate a highly significant reduction in the
      maximum load to failure from 69.5 N to 58 N in diabetic group compared to control
      (P = 0.011). Energy absorption to fracture was reduced from 28.2 N in the control
      group to 23.5 N in the diabetic group (P = 0.082). No significant differences
      were observed between the groups for bending stiffness. CONCLUSION:
      Streptozotocin-induced diabetes in rodents reduces the maximum force and energy
      absorption to failure of bone, suggesting a predisposition for fracture risk.

PMID- 23878781
TI  - Olecranon anatomy: Use of a novel proximal interlocking screw for intramedullary
      nailing, a cadaver study.
AB  - AIM: To define the optimum safe angle of use for an eccentrically aligned
      proximal interlocking screw (PIS) for intramedullary nailing (IMN). METHODS:
      Thirty-six dry cadaver ulnas were split into two equal pieces sagitally. The
      following points were identified for each ulna: the deepest point of the incisura
      olecrani (A), the point where perpendicular lines from A and the ideal IMN entry
      point (D) are intersected (C) and a point at 3.5 mm (2 mm safety distance from
      articular surface + 1.5 mm radius of PIS) posterior from point A (B). We
      calculated the angle of screws inserted from point D through to point B in
      relation to D-C and B-C. In addition, an eccentrically aligned screw was inserted
      at a standard 20 degrees  through the anterior cortex of the ulna in each bone
      and the articular surface was observed macroscopically for any damage. RESULTS:
      The mean A-C distance was 9.6 mm (mean +/- SD, 9.600 +/- 0.763 mm), A-B distance
      was 3.5 mm, C-D distance was 12.500 mm (12.500 +/- 1.371 mm) and the mean angle
      was 25.9 degrees  (25.9 degrees  +/- 2.0 degrees ). Lack of articular damage was
      confirmed macroscopically in all bones after the 20.0 degrees  eccentrically
      aligned screws were inserted. Intramedullary nail fixation systems have well
      known biological and biomechanical advantages for osteosynthesis. However, as
      well as these well-known advantages, IMN fixation of the ulna has some
      limitations. Some important limitations are related to the proximal interlocking
      of the ulna nail. The location of the PIS itself limits the indications for which
      intramedullary systems can be selected as an implant for the ulna. The new PIS
      design, where the PIS is aligned 20 degrees eccentrically to the nail body,
      allows fixing of fractures even at the level of the olecranon without disturbing
      the joint. It also allows the eccentrically aligned screw to be inserted in any
      direction except through the proximal radio-ulnar joint. Taking into
      consideration our results, we now use a 20 degrees  eccentrically aligned PIS for
      all ulnas. In our results, the angle required to insert the PIS was less than 20
      degrees  for only one bone. However, 0.7 degrees  difference corresponds to
      placement of the screw only 0.2 mm closer to the articular surface. As we assume
      2.0 mm to be a safe distance, a placement of the screw 0.2 mm closer to the
      articular surface may not produce any clinical symptoms. CONCLUSION: The new PIS
      may give us the opportunity to interlock IMN without articular damage and
      confirmation by fluoroscopy if the nail is manufactured with a PIS aligned at a
      20.0 degrees  fixed angle in relation to the IMN.

PMID- 23878782
TI  - Comparison of straight median sternotomy and interlocking sternotomy with respect
      to biomechanical stability.
AB  - AIM: To increase the stability of sternotomy and so decrease the complications
      because of instability. METHODS: Tests were performed on 20 fresh sheep sterna
      which were isolated from the sterno-costal joints of the ribs. Median straight
      and interlocking sternotomies were performed on 10 sterna each, set as groups 1
      and 2, respectively. Both sternotomies were performed with an oscillating saw and
      closed at three points with a No. 5 straight stainless-steel wiring. Fatigue
      testing was performed in cranio-caudal, anterio-posterior (AP) and lateral
      directions by a computerized materials-testing machine cycling between loads of 0
      to 400 N per 5 s (0.2 Hz). The amount of displacement in AP, lateral and cranio
      caudal directions were measured and also the opposing bone surface at the
      osteotomy areas were calculated at the two halves of sternum. RESULTS: The mean
      displacement in cranio-caudal direction was 9.66 +/- 3.34 mm for median
      sternotomy and was 1.26 +/- 0.97 mm for interlocking sternotomy, P < 0.001. The
      mean displacement in AP direction was 9.12 +/- 2.74 mm for median sternotomy and
      was 1.20 +/- 0.55 mm for interlocking sternotomy, P < 0.001. The mean
      displacement in lateral direction was 8.95 +/- 3.86 mm for median sternotomy and
      was 7.24 +/- 2.43 mm for interlocking sternotomy, P > 0.001. The mean surface
      area was 10.40 +/- 0.49 cm2 for median sternotomy and was 16.8 +/- 0.78 cm2 for
      interlocking sternotomy, P < 0.001. The displacement in AP and cranio-caudal
      directions is less in group 2 and it is statistically significant. Displacement
      in lateral direction in group 2 is less but it is statistically not significant.
      Surface area in group 2 is significantly wider than group 1. CONCLUSION: Our test
      results demonstrated improved primary stability and wider opposing bone surfaces
      in interlocking sternotomy compared to median sternotomy. This method may provide
      better healing and less complication rates in clinical setting, further studies
      are necessary for its clinical implications.

PMID- 23878783
TI  - Relationship of knowledge about osteoporosis with education level and life
      habits.
AB  - AIM: To assess possible relationships of knowledge and related factors with
      educational level and osteoporosis-related life habits. METHODS: This was a cross
      sectional study conducted on 268 women (>= 35 years old) from June 2011 to August
      2011. The sample collection was done in outpatient clinics in three university
      hospitals in Isfahan, Iran. We used a demographic questionnaire containing
      questions that evaluated osteoporosis-related life habits, including exercise,
      smoking, intake of calcium and vitamin D supplements and so on. We also used the
      Osteoporosis Knowledge Assessment Tool to measure osteoporosis knowledge of
      women. RESULTS: The mean level of knowledge about awareness of osteoporosis, its
      risk factors and preventive factors were 56, 55 and 22, respectively. The
      relationship of education level and awareness of osteoporosis, its risk factors
      and preventive factors was significant, with R = 0.76, R = 0.73 and R = 0.83,
      respectively (P < 0.001). The relationship of education level and osteoporosis
      related life habits was not significant (R = 0.03 and P = 0.56). The relationship
      of osteoporosis-related life habits and awareness of osteoporosis and its risk
      factors was significant, with R = 16%, P = 0.006 and R = 16%, P = 0.008,
      respectively, but the relationship of osteoporosis-related life habits and
      preventive factors was not significant (R = 0, P = 0.99). CONCLUSION: Iranian
      women with a higher education level have significantly better knowledge about
      osteoporosis than women with a lower educational level but they do not use this
      knowledge in their life.

PMID- 23878785
TI  - Profunda femoris artery pseudoaneurysm following revision for femoral shaft
      fracture nonunion.
AB  - Femoral artery pseudoaneurysms (FAPs) have been described following internal
      fixation of intertrocantheric, subtrocantheric and intracapsular femoral neck
      fractures as well as core decompression of the femoral head. The diagnosis of FAP
      is usually delayed because of non-specific clinical features like pain,
      haematoma, swelling, occasional fever and unexplained anaemia. Because of the
      insidious onset and of the possible delayed presentation of pseudoaneurysms,
      orthopaedic and trauma surgeons should be aware of this complication. We report a
      case of Profunda Femoris arterial branch pseudoaneurysm, diagnosed in a 40-year
      old male 4 wk after revision with Kuntscher intramedullary nail of a femoral
      shaft nonunion. The diagnosis was achieved by computed tomography angiography and
      the lesion was effectively managed by endovascular repair. The specific
      literature and suggestions for treatment are discussed in the paper. 

PMID- 23878784
TI  - Ponseti method compared with soft-tissue release for the management of clubfoot:
      A meta-analysis study.
AB  - AIM: To compare the functional outcomes of patients who underwent open surgery vs
      Ponseti method for the management of idiopathic clubfoot and to determine whether
      correlations exist between functional outcome and radiographic measurements.
      METHODS: A meta-analysis of the literature was conducted for studies concerning
      primary treatment of patients with idiopathic clubfoot. We searched PubMed
      Medline, EMBASE, and the Cochrane Library databases from January 1950 to October
      2011. Meta-analyses were performed on outcomes from 12 studies. Pooled means,
      SDs, and sample sizes were either identified in the results or calculated based
      on the results of each study. RESULTS: Overall, 835 treated idiopathic clubfeet
      in 516 patients were reviewed. The average follow-up was 15.7 years. Patients
      managed with Ponseti method did have a higher rate of excellent or good outcome
      than patients treated with open surgery (0.76 and 0.62, respectively), but not
      quite to the point of statistical significance (Q = 3.73, P = 0.053). Age at
      surgery was not correlated with the functional outcome for the surgically treated
      patients (r = -0.32, P = 0.68). A larger anteroposterior talocalcaneal angle was
      correlated with a higher rate of excellent or good outcomes (r = 0.80, P =
      0.006). There were no other significant correlations between the functional and
      radiographic outcomes. CONCLUSION: The Ponseti method should be considered the
      initial treatment of idiopathic clubfeet, and open surgery should be reserved for
      clubfeet that cannot be completely corrected.

PMID- 23878786
TI  - Solid fusion after lumbosacral arthroplasty.
AB  - A 55-year-old female was diagnosed with L5-S1 degenerative disc disease (DDD).
      Initial scores by the visual analogue scale (VAS) were 5 (back) and 9 (leg) and
      the Oswestry disability index (ODI) was 32. Arthroplasty was performed. Clinical
      and radiographic monitoring took place thereafter at one month, three months, six
      months and annually. At one month, VAS scores were 2 (back) and 3 (leg), ODI was
      12 and ROM was 2.1 degrees  by radiographs. At two years, VAS scores were 1
      (back) and 2 (leg), ODI was 6 and ROM was approaching 0. Five years after
      surgery, the entire operated segment (L5-S1) was solidly fused. A malpositioned
      disc implant may impair normal spinal movement, culminating in heterotopic
      ossification or complete fusion of the operated segment. 

PMID- 23878787
TI  - Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy.
AB  - It seems solid tumors are developing smart organs with specialized cells creating
      specified bio-territory, the so called "tumor microenvironment (TME)", in which
      there is reciprocal crosstalk among cancer cells, immune system cells and stromal
      cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that
      can resist against chemotherapies. In solid tumors, metabolism and
      vascularization appears to be aberrant and tumor interstitial fluid (TIF)
      functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene
      therapy often fail to provide cogent clinical outcomes. It looms that it is the
      time to accept the fact that initiation of cancer could be generation of another
      form of life that involves a cluster of thousands of genes, while we have failed
      to observe all aspects of it. Hence, the current treatment modalities need to be
      re-visited to cover all key aspects of disease using combination therapy based on
      the condition of patients. Perhaps personalized cluster of genes need to be
      simultaneously targeted. 

PMID- 23878789
TI  - Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D
      Breast Cancer Cell Line.
AB  - Introduction : Nowadays, using drug delivery is an essential method to improve
      cancer therapy through decreasing drug toxicity and increasing efficiency of
      treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from
      the milk thistle plant, has various applications in cancer therapy but it has
      hydrophobic structure with low water solubility and bioavailability. To increase
      the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to
      determine the inhibitory effect of this nanodrug on Telomerase gene expression.
      Methods : The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then,
      the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl
      Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene
      expression was indicated through Real-time PCR. Results : Data analysis from MTT
      assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic
      effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG
      Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the
      level of telomerase gene expression more efficiently decreased with silibinin
      loaded PLGA-PEG-Fe3O4 than with free silibinin alone. Conclusion : The present
      study indicates that this nanodrug causes down-regulation of Telomerase gene
      expression in cancer cells. Therefore, PLGA-PEG-Fe3O4 could be an appropriate
      carrier for hydrophobic agents such as silibinin to improve their action in
      cancer therapy. 

PMID- 23878788
TI  - Nanomaterials as Non-viral siRNA Delivery Agents for Cancer Therapy.
AB  - Gene therapy has been recently shown as a promising tool for cancer treatment as
      nanotechnology-based safe and effective delivery methods are developed.
      Generally, genes are wrapped up in extremely tiny nanoparticles which could be
      taken up easily by cancer cells, not to their healthy neighboring cells. Several
      nanoparticle systems have been investigated primarily to address the problems
      involved in other methods of gene delivery and observed improved anticancer
      efficacy suggesting that nanomedicine provides novel opportunities to safely
      deliver genes, thus treat cancer. In this review, various nanoparticle types and
      related strategies, used in gene delivery for cancer treatment, have been
      discussed. 

PMID- 23878790
TI  - Application of response surface methodology in development of sirolimus liposomes
      prepared by thin film hydration technique.
AB  - Introduction : The present investigation was aimed to optimize the formulating
      process of sirolimus liposomes by thin film hydration method. Methods : In this
      study, a 3(2) factorial design method was used to investigate the influence of
      two independent variables in the preparation of sirolimus liposomes. The
      dipalmitoylphosphatidylcholine (DPPC) /Cholesterol (Chol) and dioleoyl
      phosphoethanolamine(DOPE) /DPPC molar ratios were selected as the independent
      variables. Particle size (PS) and Encapsulation Efficiency (EE %) were selected
      as the dependent variables. To separate the un-encapsulated drug, dialysis method
      was used. Drug analysis was performed with a validated RP-HPLC method. Results :
      Using response surface methodology and based on the coefficient values obtained
      for independent variables in the regression equations, it was clear that the
      DPPC/Chol molar ratio was the major contributing variable in particle size and EE
      %. The use of a statistical approach allowed us to see individual and/or
      interaction effects of influencing parameters in order to obtain liposomes with
      desired properties and to determine the optimum experimental conditions that lead
      to the enhancement of characteristics. In the prediction of PS and EE % values,
      the average percent errors are found to be as 3.59 and 4.09%. This value is
      sufficiently low to confirm the high predictive power of model. Conclusion :
      Experimental results show that the observed responses were in close agreement
      with the predicted values and this demonstrates the reliability of the
      optimization procedure in prediction of PS and EE % in sirolimus liposomes
      preparation. 

PMID- 23878792
TI  - A prospective study of inpatients to determine microbial etiology and therapeutic
      outcome of antibiotics for community-acquired pneumonia in pakistan.
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) is among the common diseases
      that causes illness and death world-wide. Limited data is available for the
      treatment of patients with CAP and/or medical outcome of CAP patients in
      Pakistan. This cross-sectional and prospective study was done to determine
      etiology of CAP patients and to evaluate the therapeutic effects of antibiotics
      commonly used in treating CAP patients in two different inner-city hospitals,
      Pakistan. METHODS: The study was conducted on 200 hospitalized patients
      presenting clinical and radiographic evidences of CAP. The patients were assessed
      for the causative pathogen and their prescriptions were analyzed for the
      management and treatment of CAP and associated symptoms of pneumonia. Finally the
      medical outcomes were evaluated. RESULTS: On establishing the microbial etiology
      of pneumonia among different CAP causing pathogens, K. pneumoniae was found to be
      the most identified causative agent (30%) followed by S. pneumoniae (23%).
      Majority of the patients received cephalosporin antibiotics (80%) followed by
      aminoglycosides (65%) and penicillins (50%) either as monotherapy or combination
      treatment. Therapeutic success was observed to occur in majority of the patients.
      The recovery of CAP patients occurred probably because they received antibiotics
      which are recommended by WHO and American Thoracic Society. Another reason for
      successful therapeutic outcome was found to be the significant patient compliance
      for treatment. CONCLUSION: There is a great need for such types of
      investigational studies to be conducted in developing countries which may guide
      the empirical therapy and help in defining proper treatment guidelines.

PMID- 23878791
TI  - Epicardial and subcutaneous adipose tissue Fatty acids profiles in diabetic and
      non-diabetic patients candidate for coronary artery bypass graft.
AB  - INTRODUCTION: We have recently shown that in high cholesterol-fed rabbits, the
      sensitivity of epicardial adipose tissue to changes in dietary fat is higher than
      that of subcutaneous adipose tissue. Although the effects of diabetes on
      epicardial adipose tissue thickness have been studied, the influence of diabetes
      on profile of epicardial free fatty acids (FFAs) has not been studied. The aim of
      this study is to investigate the effect of diabetes on the FFAs composition in
      serum and in the subcutaneous and epicardial adipose tissues in patients
      undergoing coronary artery bypass graft (CABG). METHODS: Forty non-diabetic and
      twenty eight diabetic patients candidate for CABG with >75% stenosis participated
      in this study. Fasting blood sugar (FBS) and lipid profiles were assayed by auto
      analyzer. Phospholipids and non-estrified FFA of serum and the fatty acids
      profile of epicardial and subcutaneous adipose tissues were determined using gas
      chromatography method. RESULTS: In the phospholipid fraction of diabetic
      patients' serum, the percentage of 16:0, 18:3n-9, 18:2n-6 and monounsaturated
      fatty acids (MUFAs) was lower than the corresponding values of the non-diabetics;
      whereas, 18:0 value was higher. A 100% increase in the amount of 18:0 and 35%
      decrease in the level of 18:1n-11 was observed in the diabetic patients'
      subcutaneous adipose tissue. In epicardial adipose tissue, the increase of 18:0
      and conjugated linolenic acid (CLA) and decrease of 18:1n-11, w3 (20:5n-3) and
      22:6n-3 were significant; but, the contents of arachidonic acid and its precursor
      linoleic acid were not affected by diabetes. CONCLUSION: The fatty acids' profile
      of epicardial and subcutaneous adipose tissues is not equally affected by
      diabetes. The significant decrease of 16:0 and w3 fatty acids and increase of
      trans and conjugated fatty acids in epicardial adipose tissue in the diabetic
      patients may worsen the formation of atheroma in the related arteries.

PMID- 23878793
TI  - Assessment of palmitoyl and sulphate conjugated glycol chitosan for development
      of polymeric micelles.
AB  - INTRODUCTION: Amphiphilic copolymers are capable of forming core shell-like
      structures at the critical micellar concentration (CMC); hence, they can serve as
      drug carriers. Thus, in the present work, polymeric micelles based on novel
      chitosan derivative were synthesized. METHODS: Block copolymer of palmitoyl
      glycol chitosan sulfate (PGCS) was prepared by grafting palmitoyl and sulfate
      groups serving as hydrophobic and hydrophilic fractions, respectively. Then,
      fourier transform infrared spectra (FTIR) and spectral changes in iodine/iodide
      mixture were carried out. RESULTS: FTIR studies confirmed the formation of
      palmitoyl glycol chitosan sulfate (PGCS) and spectral changes in iodine/iodide
      mixture indicated CMC which lies in the range of 0.003-0.2 mg/ml. CONCLUSION:
      Therefore, our study indicated that polymeric micelles based on palmitoyl glycol
      chitosan sulphate could be used as a prospective carrier for water insoluble
      drugs.

PMID- 23878794
TI  - Effect of HEMADO on Level of CK-MB and LDH Enzymes after Ischemia/Reperfusion
      Injury in Isolated Rat Heart.
AB  - INTRODUCTION: Ischemia/Reperfusion (IR) injury mainly causes the increase of
      enzymes involved in myocytes injury including CK-MB (creatine kinase-MB)
      isoenzyme and LDH (lactate dehydrogenase). Leakage of CK-MB isoenzyme and LDH
      from myocardial tissues to blood is indicator of acute myocardial infarction. The
      aim of this study was to assess the effect of HEMADO on IR injury and its
      relationship with mitochondrial ATP-sensitive K+ channels (mitoKATP) in rat
      heart. METHODS: Twenty eight male Wistar rats (250-300g) were divided into four
      groups (seven members in each group): control (without ischemia), I/R (with
      ischemia+without HEMADO), ischemia received HEMADO (HEMADO), ischemia received
      HEMADO and 5-HD (5-hydroxydecanoate, specific mitoKATP channel blocker) (HEMADO+5
      HD). The animals were anesthetized and the hearts were quickly removed and
      mounted on Langendorff apparatus and perfused by Krebs-Henseleit solution under
      constant pressure and temperature of 37oC. After 20 minutes of stabilization,
      ischemic groups were exposed to 40 minutes of global ischemia and consecutive 90
      minutes of reperfusion. RESULTS: IR injury increased the level of LDH and CK-MB
      in the collected coronary flow during 5 minutes since start of reperfusion.
      HEMADO reduced the enzymes' levels and using 5-HD abolished the effect of HEMADO.
      CONCLUSION: Our findings indicated that HEMADO could protect the heart against
      ischemia-reperfusion injury by decreasing the CK-MB and LDH levels. The
      cardioprotective effect of HEMADO may be mediated in part by mitoKATP.

PMID- 23878795
TI  - Correlation between phylogroups and intracellular proteomes of Propionibacterium
      acnes and differences in the protein expression profiles between anaerobically
      and aerobically grown cells.
AB  - Propionibacterium acnes is one of the dominant commensals on the human skin and
      also an opportunistic pathogen in relation to acne, sarcoidosis, prostate cancer,
      and various infections. Recent investigations using housekeeping and virulence
      genes have revealed that the species consists of three major evolutionary clades
      (types I, II, and III). In order to investigate protein expression differences
      between these phylogroups, proteomic profiles of 21 strains of P. acnes were
      investigated. The proteins extracted from cells cultured under anaerobic and
      aerobic conditions were analysed using a SELDI-TOF mass spectrometer, high
      resolution capillary gel electrophoresis, and LC-MS/ MS. The SELDI spectral
      profiles were visualised as a heat map and a dendrogram, which resulted in four
      proteomic groups. Strains belonging to type I were represented in the proteome
      Group A, while Group B contained type III strains. Groups C and D contained
      mixtures of types I and II. Each of these groups was not influenced by
      differences in culture conditions. Under anoxic growth conditions, a type IB
      strain yielded high expressions of some proteins, such as methylmalonyl-CoA
      epimerase and the Christie-Atkins-Munch-Petersen (CAMP) factor. The present study
      revealed good congruence between genomic and proteomic data suggesting that the
      microenvironment of each subtype may influence protein expression. 

PMID- 23878796
TI  - Genetic variation between Biomphalaria alexandrina snails susceptible and
      resistant to Schistosoma mansoni infection.
AB  - Much effort has been made to control schistosomiasis infection in Egypt. However,
      enduring effects from such strategies have not yet been achieved. In this study,
      we sought to determine the genetic variability related to the interaction between
      Biomphalaria alexandrina snails and Schistosoma mansoni. Using RAPD-PCR with
      eight (10 mers) random primers, we were able to determine the polymorphic markers
      that differed between snails susceptible and resistant to Schistosoma mansoni
      infection using five primers out of the eight. Our results suggest that the RAPD
      PCR technique is an efficient means by which to compare genomes and to detect
      genetic variations between schistosomiasis intermediate hosts. The RAPD technique
      with the above-noted primers can identify genomic markers that are specifically
      related to the Biomphalaria alexandrina/Schistosoma mansoni relationship in the
      absence of specific nucleotide sequence information. This approach could be used
      in epidemiologic surveys to investigate genetic diversity among Biomphalaria
      alexandrina snails. The ability to determine resistant markers in Biomphalaria
      alexandrina snails could potentially lead to further studies that use refractory
      snails as agents to control the spread of schistosomiasis.

PMID- 23878797
TI  - Role of dopaminergic receptors in glaucomatous disease modulation.
AB  - Both studies on animals and humans suggest the presence of dopamine (DA)
      receptors in the anterior segment of the eye. Their role in the dynamics of
      intraocular pressure (IOP) is not yet clear. DA2 and DA3 receptors are mainly
      located on postganglionic sympathetic nerve endings. Their stimulation reduces
      the release of norepinephrine and suppresses the production of aqueous humor. DA1
      receptors seem to be more expressed by the ciliary body and the outflow pathway
      of aqueous humor. The administration of DA1-selective agonists stimulates the
      production of aqueous humor, increasing IOP, whereas DA2- and DA3-selective
      agonists could reduce IOP and, therefore, the risk to develop a glaucoma (GL). GL
      is a broad spectrum of eye diseases which have in common the damage to the optic
      nerve and the progressive loss of the visual field. Further studies are desirable
      to clarify the role of the dopaminergic system and the usefulness of DA2 and DA3
      agonists in reducing IOP. 

PMID- 23878798
TI  - Candida infections, causes, targets, and resistance mechanisms: traditional and
      alternative antifungal agents.
AB  - The genus Candida includes about 200 different species, but only a few species
      are human opportunistic pathogens and cause infections when the host becomes
      debilitated or immunocompromised. Candida infections can be superficial or
      invasive. Superficial infections often affect the skin or mucous membranes and
      can be treated successfully with topical antifungal drugs. However, invasive
      fungal infections are often life-threatening, probably due to inefficient
      diagnostic methods and inappropriate initial antifungal therapies. Here, we
      briefly review our current knowledge of pathogenic species of the genus Candida
      and yeast infection causes and then focus on current antifungal drugs and
      resistance mechanisms. An overview of new therapeutic alternatives for the
      treatment of Candida infections is also provided. 

PMID- 23878799
TI  - Metabolomic analysis of differential changes in metabolites during ATP
      oscillations in chondrogenesis.
AB  - Prechondrogenic condensation is a critical step for skeletal pattern formation.
      Recent studies reported that ATP oscillations play an essential role in
      prechondrogenic condensation. However, the molecular mechanism to underlie ATP
      oscillations remains poorly understood. In the present study, it was investigated
      how changes in metabolites are implicated in ATP oscillations during
      chondrogenesis by using capillary electrophoresis time-of-flight mass
      spectrometry (CE-TOF-MS). CE-TOF-MS detected 93 cationic and 109 anionic
      compounds derived from known metabolic pathways. 15 cationic and 18 anionic
      compounds revealed significant change between peak and trough of ATP
      oscillations. These results implicate that glycolysis, mitochondrial respiration
      and uronic acid pathway oscillate in phase with ATP oscillations, while PPRP and
      nucleotides synthesis pathways oscillate in antiphase with ATP oscillations. This
      suggests that the ATP-producing glycolysis and mitochondrial respiration
      oscillate in antiphase with the ATP-consuming PPRP/nucleotide synthesis pathway
      during chondrogenesis. 

PMID- 23878800
TI  - Meta-analysis of microarray data identifies GAS6 expression as an independent
      predictor of poor survival in ovarian cancer.
AB  - Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause
      of death from all cancers in women and the leading cause of death from
      gynaecological malignancies, we performed a meta-analysis of three independent
      studies and compared the results in regard to clinicopathological parameters.
      This analysis revealed that GAS6 was highly expressed in ovarian cancer and
      therefore was selected as our candidate of choice. GAS6 encodes a secreted
      protein involved in physiological processes including cell proliferation,
      chemotaxis, and cell survival. We performed immunohistochemistry on various
      ovarian cancer tissues and found that GAS6 expression was elevated in tumour
      tissue samples compared to healthy control samples (P < 0.0001). In addition,
      GAS6 expression was also higher in tumours from patients with residual disease
      compared to those without. Our data propose GAS6 as an independent predictor of
      poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a
      potential biomarker for ovarian cancer. In clinical practice, the staining of a
      tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor
      disease progression. 

PMID- 23878801
TI  - Protein coexpression using FMDV 2A: effect of "linker" residues.
AB  - Many biomedical applications absolutely require, or are substantially enhanced
      by, coexpression of multiple proteins from a single vector. Foot-and-mouth
      disease virus 2A (F2A) and "2A-like" sequences (e.g., Thosea asigna virus 2A;
      T2A) are used widely for this purpose since multiple proteins can be coexpressed
      by linking open reading frames (ORFs) to form a single cistron. The activity of
      F2A "cleavage" may, however, be compromised by both the use of shorter versions
      of F2A and the sequences (derived from multiple-purpose cloning sites) used to
      link F2A to the upstream protein. To characterise these effects, different
      lengths of F2A and T2A were inserted between green and cherry fluorescent
      proteins. Mutations were introduced in the linker region immediately upstream of
      both F2A- and T2A-based constructs and activities determined using both cell-free
      translation systems and transfected cells. In shorter versions of F2A, activity
      may be affected by both the C-terminal sequence of the protein upstream and,
      equally strikingly, the residues immediately upstream introduced during cloning.
      Mutations significantly improved activity for shorter versions of F2A but could
      decrease activity in the case of T2A. These data will aid the design of cloning
      strategies for the co-expression of multiple proteins in
      biomedical/biotechnological applications. 

PMID- 23878803
TI  - Comparative study of various delivery methods for the supply of alpha
      ketoglutarate to the neural cells for tissue engineering.
AB  - Delivery of growth factors or bioactive molecules plays an important role in
      tissue engineering, as the duration to which these are supplied can modulate the
      cell fate. Thus, the delivery method plays an important role, and the same is
      presented in this work wherein the exogenous supply of alpha-ketoglutarate (
      alpha -KG) gave better results for fast proliferating cells as compared to
      delivery by microspheres or microspheres incorporated scaffolds which can be used
      while culturing slow growing cells. All these studies were performed in two
      dimensional (2D) and three dimensional (3D) setups in which chitosan-gelatin
      polypyrrole has been used as 3-D scaffolds. Chitosan and gelatin microspheres
      alone as well as incorporated in the cryogels were characterized. MTT assay done
      using neuro-2a cell line showed approximately 42% and 70% increment in cellular
      proliferation when gelatin and chitosan microspheres were added in a 3-D setup,
      respectively, as compared to the control. Biochemical analysis of ammonia showed
      6-fold reductions in ammonia level in a 3-D setup compared to the control. We
      also studied the synthesis of a neurotransmitter-like glutamate and found that
      its concentration increased up to 0.25 mg/ml when the microspheres were added
      exogenously in a 3-D system.

PMID- 23878802
TI  - MicroRNAs: new insights into chronic childhood diseases.
AB  - Chronic diseases are the major cause of morbidity and mortality worldwide and
      have shown increasing incidence rates among children in the last decades. Chronic
      illnesses in the pediatric population, even if well managed, affect social,
      psychological, and physical development and often limit education and active
      participation and increase the risk for health complications. The significant
      pediatric morbidity and mortality rates caused by chronic illnesses call for
      serious efforts toward better understanding of the pathogenesis of these
      disorders. Recent studies have shown the involvement of microRNAs (miRNAs) in
      various aspects of major pediatric chronic non-neoplastic diseases. This review
      focuses on the role of miRNAs in four major pediatric chronic diseases including
      bronchial asthma, diabetes mellitus, epilepsy and cystic fibrosis. We intend to
      emphasize the importance of miRNA-based research in combating these major
      disorders, as we believe this approach will result in novel therapies to aid
      securing normal development and to prevent disabilities in the pediatric
      population. 

PMID- 23878804
TI  - Echocardiography in the era of multimodality cardiovascular imaging.
AB  - Echocardiography remains the most frequently performed cardiac imaging
      investigation and is an invaluable tool for detailed and accurate evaluation of
      cardiac structure and function. Echocardiography, nuclear cardiology, cardiac
      magnetic resonance imaging, and cardiovascular-computed tomography comprise the
      subspeciality of cardiovascular imaging, and these techniques are often used
      together for a multimodality, comprehensive assessment of a number of cardiac
      diseases. This paper provides the general cardiologist and physician with an
      overview of state-of-the-art modern echocardiography, summarising established
      indications as well as highlighting advances in stress echocardiography, three
      dimensional echocardiography, deformation imaging, and contrast echocardiography.
      Strengths and limitations of echocardiography are discussed as well as the
      growing role of real-time three-dimensional echocardiography in the guidance of
      structural heart interventions in the cardiac catheter laboratory. 

PMID- 23878805
TI  - The effect of chlorpyrifos on isolated thoracic aorta in rats.
AB  - This study investigated the effect of chlorpyrifos on thoracic aorta and on the
      level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in
      organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups
      with 15 rats each: control group 1 received distilled water, control group 2 was
      given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in
      corn oil every other day for 8 weeks orally. Chlorpyrifos (10(-10) M-10(-5) M)
      showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased,
      while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group
      compared to control groups. Plasma NO level was increased in chlorpyrifos group
      compared to control groups. iNOS expression was present in all groups in the
      cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to
      semiquantitative histomorphological analysis, iNOS immunopositive reactions were
      seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups.
      eNOS immunopositive reactions were observed in the endothelial cell cytoplasm,
      rarely in the subintimal layer, and the smooth muscle cells of aorta. There were
      no differences among the groups in terms of eNOS immunostaining. In conclusion,
      chlorpyrifos induced NO production in aorta following an increase in NOS
      expression.

PMID- 23878806
TI  - Expression and in Silico analysis of the recombinant bovine papillomavirus E6
      protein as a model for viral oncoproteins studies.
AB  - Bovine papillomaviruses (BPVs) are recognized as the causal agents of economical
      relevant diseases in cattle, associated with the development of tumors in skin
      and mucosa. The oncogenesis process is mainly associated with different viral
      oncoprotein expressions, which are involved in cell transformation. The
      expression and characterization of recombinant viral oncoproteins represent an
      attractive strategy to obtain biotechnological products as antibodies and
      potential vaccines, Thus, the aim of this work was to clone and express the BPV-1
      and BPV-2 E6 recombinant proteins and perform in silico analysis in order to
      develop a strategy for the systematic study of other papillomaviruses
      oncoproteins. The results demonstrated that BPV-1 and BPV-2 E6 recombinant
      proteins were expressed and purified from bacterial system as well as its in
      silico analysis was performed in order to explore and predict biological
      characteristics of these proteins. 

PMID- 23878807
TI  - Natural Killer Dendritic Cells Enhance Immune Responses Elicited by alpha 
      Galactosylceramide-Stimulated Natural Killer T Cells.
AB  - Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but
      the cellular effect of NKDC interactions with other innate immune cells is
      unclear. In this study, we demonstrate that the interaction of NKDCs and natural
      killer T (NKT) cells is required for the anti-tumor immune responses that are
      elicited by alpha -galactosylceramide ( alpha -GC) in mice. The rapid and strong
      expression of interferon- gamma by NKDCs after alpha -GC stimulation was
      dependent on NKT cells. Various NK and DC molecular markers and cytotoxic
      molecules were up-regulated following alpha -GC administration. This up
      regulation could improve NKDC presentation of tumor antigens and increase
      cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs,
      NK cells, and NKT cells. The strong anti-tumor immune responses elicited by alpha
      -GC may be due to the down-regulation of regulatory T cells. Furthermore, the
      depletion of NKDCs dampened the tumor clearance mediated by alpha -GC-stimulated
      NKT cells in vivo. Taken together, these results indicate that complex
      interactions of innate immune cells might be required to achieve optimal anti
      tumor immune responses during the early stages of tumorigenesis. 

PMID- 23878808
TI  - Whole blood platelet aggregation and release reaction testing in uremic patients.
AB  - BACKGROUND: Platelet function analysis utilizing platelet-rich plasma and optical
      density based aggregometry fails to identify patients at risk for uremia
      associated complications. METHODS: We employed whole blood platelet aggregation
      analysis based on impedance as well as determination of ATP release from platelet
      granules detected by a chemiluminescence method. Ten chronic kidney disease (CKD)
      stage 4 or 5 predialysis patients underwent platelet evaluation. Our study aims
      to evaluate this platform in this patient population to determine if
      abnormalities could be detected. RESULTS: Analysis revealed normal aggregation
      and ATP release to collagen, ADP, and high-dose ristocetin. ATP release had a low
      response to arachidonic acid (0.37 +/- 0.26 nmoles, reference range: 0.6-1.4
      nmoles). Platelet aggregation to low-dose ristocetin revealed an exaggerated
      response (20.9 +/- 18.7 ohms, reference range: 0-5 ohms). CONCLUSIONS: Whole
      blood platelet analysis detected platelet dysfunction which may be associated
      with bleeding and thrombotic risks in uremia. Diminished ATP release to
      arachidonic acid (an aspirin-like defect) in uremic patients may result in
      platelet associated bleeding. An increased aggregation response to low-dose
      ristocetin (a type IIb von Willebrand disease-like defect) is associated with
      thrombus formation. This platelet hyperreactivity may be associated with a
      thrombotic diathesis as seen in some uremic patients.

PMID- 23878809
TI  - Khat chewing among students of higher education in Jazan region, Saudi Arabia:
      prevalence, pattern, and related factors.
AB  - OBJECTIVES: (1) To estimate the prevalence and behavioral patterns of Khat
      chewing and (2) to investigate factors that influenced the pattern of Khat use
      among undergraduate students in different higher education institutions in Jazan
      region, Saudi Arabia. MATERIALS AND METHODS: A cross-sectional study using a
      pretested structured self-administered quantitative questionnaire was used to
      collect data. SPSS version 17 software program was used for data analysis.
      RESULTS: The overall current Khat chewing prevalence among higher education
      students was found to be 23.1%, significantly higher among males at 38.5% than
      among females at 2.1% (P < 0.001). Lifetime Khat chewer students were 24.8% for
      males at 40.5%, significantly higher compared with females at 3.7% (P < 0.001).
      Univariate analysis revealed that the gender of student, smoking status of
      student, a friend's smoking, and Khat chewing were associated with a significant
      high risk of Khat chewing (P < 0.001   for all). CONCLUSIONS: The use of Khat
      trend is increasing among higher education students in Jazan region. A
      multilevel, value based, comprehensive, and strategic long-term intervention plan
      is needed. The comprehensive plan may include social interventions geared by
      creating recreations alternatives and opportunities for youth and a critical
      review for current authorities' interventions and services.

PMID- 23878810
TI  - Plant growth promotion potential is equally represented in diverse grapevine root
      associated bacterial communities from different biopedoclimatic environments.
AB  - Plant-associated bacteria provide important services to host plants.
      Environmental factors such as cultivar type and pedoclimatic conditions
      contribute to shape their diversity. However, whether these environmental factors
      may influence the plant growth promoting (PGP) potential of the root-associated
      bacteria is not widely understood. To address this issue, the diversity and PGP
      potential of the bacterial assemblage associated with the grapevine root system
      of different cultivars in three Mediterranean environments along a macrotransect
      identifying an aridity gradient were assessed by culture-dependent and
      independent approaches. According to 16S rRNA gene PCR-DGGE, the structure of
      endosphere and rhizosphere bacterial communities was highly diverse (P = 0.03)
      and was associated with a cultivar/latitudinal/climatic effect. Despite being
      diverse, the bacterial communities associated with Egyptian grapevines shared a
      higher similarity with the Tunisian grapevines than those cultivated in North
      Italy. A similar distribution, according to the cultivar/latitude/aridity
      gradients, was observed for the cultivable bacteria. Many isolates (23%)
      presented in vitro multiple stress resistance capabilities and PGP activities,
      the most frequent being auxin synthesis (82%), insoluble phosphate solubilisation
      (61%), and ammonia production (70%). The comparable numbers and types of
      potential PGP traits among the three different environmental settings indicate a
      strong functional homeostasis of beneficial bacteria associated with grape root. 

PMID- 23878811
TI  - Factors associated within 28 days in-hospital mortality of patients with acute
      respiratory distress syndrome.
AB  - OBJECTIVE: To determine the factors leading to in-hospital mortality within 28
      days in hospitalized patients with ARDS. It was a prospective observational
      cohort study conducted in Intensive Care Unit of Aga Khan University Hospital
      Karachi from March to August 2011. METHODOLOGY: Data was collected from patients
      admitted in the intensive care unit on the basis of inclusion and exclusion
      criteria. The patients were followed daily for 28 days to record any in-hospital
      complications and the outcome of patients. RESULTS: Total of 46 patients were
      included during this period out of which 56% (26) were males and 43% (20) were
      females. Mean age was 44 +/- 19 years. There were 11 (23.9%) patients with age
      >65 and 35 (76%) had age <65 years. There were 21 (45.6%) patients with pulmonary
      ARDS and 25 (54.3%) had extrapulmonary ARDS. APACHE II score of >20 was present
      in 23 (50%) patients while the rest had score of <20. Regarding in-hospital
      complications, 23 (50%) patients developed sepsis, 31 (67.4%) had multiorgan
      failure, 14 (30%) had refractory shock, and 15 (32.6%) developed refractory
      hypoxemia. Out of 46 patients, 26 (56.5%) died within 28 days. On univariate
      analysis, high APACHE score, multiorgan failure, refractory shock, and refractory
      hypoxemia were main causes of death. CONCLUSION: ARDS is a syndrome of high
      mortality with mortality rate of 56.5% in this study. High APACHE, sepsis,
      multiorgan failure, refractory shock, and refractory hypoxemia are the leading
      causes of death in our patients.

PMID- 23878814
TI  - Application of improved three-dimensional kernel approach to prediction of
      protein structural class.
AB  - Kernel methods, such as kernel PCA, kernel PLS, and support vector machines, are
      widely known machine learning techniques in biology, medicine, chemistry, and
      material science. Based on nonlinear mapping and Coulomb function, two 3D kernel
      approaches were improved and applied to predictions of the four protein tertiary
      structural classes of domains (all- alpha , all- beta , alpha / beta , and alpha 
      +  beta ) and five membrane protein types with satisfactory results. In a
      benchmark test, the performances of improved 3D kernel approach were compared
      with those of neural networks, support vector machines, and ensemble algorithm.
      Demonstration through leave-one-out cross-validation on working datasets
      constructed by investigators indicated that new kernel approaches outperformed
      other predictors. It has not escaped our notice that 3D kernel approaches may
      hold a high potential for improving the quality in predicting the other protein
      features as well. Or at the very least, it will play a complementary role to many
      of the existing algorithms in this regard. 

PMID- 23878813
TI  - Evaluating phylogenetic informativeness as a predictor of phylogenetic signal for
      metazoan, fungal, and mammalian phylogenomic data sets.
AB  - Phylogenetic research is often stymied by selection of a marker that leads to
      poor phylogenetic resolution despite considerable cost and effort. Profiles of
      phylogenetic informativeness provide a quantitative measure for prioritizing gene
      sampling to resolve branching order in a particular epoch. To evaluate the
      utility of these profiles, we analyzed phylogenomic data sets from metazoans,
      fungi, and mammals, thus encompassing diverse time scales and taxonomic groups.
      We also evaluated the utility of profiles created based on simulated data sets.
      We found that genes selected via their informativeness dramatically outperformed
      haphazard sampling of markers. Furthermore, our analyses demonstrate that the
      original phylogenetic informativeness method can be extended to trees with more
      than four taxa. Thus, although the method currently predicts phylogenetic signal
      without specifically accounting for the misleading effects of stochastic noise,
      it is robust to the effects of homoplasy. The phylogenetic informativeness
      rankings obtained will allow other researchers to select advantageous genes for
      future studies within these clades, maximizing return on effort and investment.
      Genes identified might also yield efficient experimental designs for phylogenetic
      inference for many sister clades and outgroup taxa that are closely related to
      the diverse groups of organisms analyzed. 

PMID- 23878812
TI  - Molecular functions of thyroid hormones and their clinical significance in liver
      related diseases.
AB  - Thyroid hormones (THs) are potent mediators of several physiological processes,
      including embryonic development, cellular differentiation, metabolism, and cell
      growth. Triiodothyronine (T3) is the most biologically active TH form. Thyroid
      hormone receptors (TRs) belong to the nuclear receptor superfamily and mediate
      the biological functions of T3 via transcriptional regulation. TRs generally form
      heterodimers with the retinoid X receptor (RXR) and regulate target genes upon T3
      stimulation. Research over the past few decades has revealed that disruption of
      cellular TH signaling triggers chronic liver diseases, including alcoholic or
      nonalcoholic fatty liver disease and hepatocellular carcinoma (HCC). Animal model
      experiments and epidemiologic studies to date imply close associations between
      high TH levels and prevention of liver disease. Moreover, several investigations
      spanning four decades have reported the therapeutic potential of T3 analogs in
      lowering lipids, preventing chronic liver disease, and as anticancer agents.
      Thus, elucidating downstream genes/signaling pathways and molecular mechanisms of
      TH actions is critical for the treatment of significant public health issues.
      Here, we have reviewed recent studies focusing on the roles of THs and TRs in
      several disorders, in particular, liver diseases. We also discuss the potential
      therapeutic applications of THs and underlying molecular mechanisms. 

PMID- 23878815
TI  - Persistent organic pollutants induced protein expression and
      immunocrossreactivity by Stenotrophomonas maltophilia PM102: a prospective
      bioremediating candidate.
AB  - A novel bacterium capable of growth on trichloroethylene as the sole carbon
      source was identified as Stenotrophomonas maltophilia PM102 by 16S rDNA
      sequencing (accession number of NCBI GenBank: JQ797560). In this paper, we report
      the growth pattern, TCE degradation, and total proteome of this bacterium in
      presence of various other carbon sources: toluene, phenol, glucose, chloroform,
      and benzene. TCE degradation was comparatively enhanced in presence of benzene.
      Densitometric analysis of the intracellular protein profile revealed four
      proteins of 78.6, 35.14, 26.2, and 20.47 kDa while the extracellular protein
      profile revealed two distinct bands at 14 kDa and 11 kDa that were induced by
      TCE, benzene, toluene, and chloroform but absent in the glucose lane. A rabbit
      was immunised with the total protein extracted from the bacteria grown in 0.2%
      TCE + 0.2% peptone. Antibody preadsorbed on proteins from peptone grown PM102
      cells reacted with a single protein of 35.14 kDa (analysed by MALDI-TOF-mass
      spectrometry) from TCE, benzene, toluene, or chloroform grown cells. No reaction
      was seen for proteins of PM102 grown with glucose. The PM102 strain was
      immobilised in calcium alginate beads, and TCE degradation by immobilised cells
      was almost double of that by free cells. The beads could be reused 8 times.

PMID- 23878816
TI  - Therapeutic application of cardiac stem cells and other cell types.
AB  - Various researches on regenerative medicine were carried out experimentally, and
      selected modalities have been introduced to the clinical arena. Meanwhile, the
      presence of resident stem cells in the heart and their role in physiological cell
      turnover were demonstrated. So far skeletal myoblasts, bone marrow-derived cells,
      mesenchymal stromal cells, and resident cardiac cells have been applied for
      therapeutic myocardial regeneration. Among them, autologous transplantation of c
      kit-positive cardiac stem cells in congestive heart failure patients resulted in
      an outstanding outcome, with long-lasting beneficial effects without major
      adverse events. By reviewing these clinical trials, an endeavor was made to seek
      for an ideal cellular therapy for cardiovascular diseases. 

PMID- 23878817
TI  - Digestibility and IgE-binding of glycosylated codfish parvalbumin.
AB  - Food-processing conditions may alter the allergenicity of food proteins by
      different means. In this study, the effect of the glycosylation as a result of
      thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is
      investigated. Native and glycosylated parvalbumins were digested with pepsin at
      various conditions relevant for the gastrointestinal tract. Intact proteins and
      peptides were analysed for apparent molecular weight and IgE-binding.
      Glycosylation did not substantially affect the digestion. Although the peptides
      resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was
      strongly diminished. However, the glycosylated parvalbumin had a strong
      propensity to form dimers and tetramers, and these multimers bound IgE intensely,
      suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that
      glycosylation of codfish parvalbumin does not affect the digestibility of
      parvalbumin and that the peptides resulting from this digestion show low IgE
      binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the
      formation of higher order structures that are more potent IgE binders than
      native, monomeric parvalbumin. Therefore, food-processing conditions applied to
      fish allergen can potentially lead to increased allergenicity, even while the
      protein's digestibility is not affected by such processing.

PMID- 23878818
TI  - Hepatoprotective and antioxidant effects of saponarin, isolated from Gypsophila
      trichotoma Wend. on paracetamol-induced liver damage in rats.
AB  - The hepatoprotective potential of saponarin, isolated from Gypsophila trichotoma,
      was evaluated in vitro/in vivo using a hepatotoxicity model of paracetamol
      induced liver injury. In freshly isolated rat hepatocytes, paracetamol (100 MU
      mol) led to a significant decrease in cell viability, increased LDH leakage,
      decreased levels of cellular GSH, and elevated MDA quantity. Saponarin (60-0.006
      MU g/mL) preincubation, however, significantly ameliorated paracetamol-induced
      hepatotoxicity in a concentration-dependent manner. The beneficial effect of
      saponarin was also observed in vivo. Rats were challenged with paracetamol alone
      (600 mg/kg, i.p.) and after 7-day pretreatment with saponarin (80 mg/kg, oral
      gavage). Paracetamol toxicity was evidenced by increase in MDA quantity and
      decrease in cell GSH levels and antioxidant defence system. No changes in phase I
      enzyme activities of AH and EMND and cytochrome P 450 quantity were detected.
      Saponarin pretreatment resulted in significant increase in cell antioxidant
      defence system and GSH levels and decrease in lipid peroxidation. The biochemical
      changes are in good correlation with the histopathological data. Protective
      activity of saponarin was similar to the activity of positive control silymarin.
      On the basis of these results, it can be concluded that saponarin exerts
      antioxidant and hepatoprotective activity against paracetamol liver injury in
      vitro/in vivo.

PMID- 23878819
TI  - Natural treatment systems as sustainable ecotechnologies for the developing
      countries.
AB  - The purpose of natural treatment systems is the re-establishment of disturbed
      ecosystems and their sustainability for benefits to human and nature. The working
      of natural treatment systems on ecological principles and their sustainability in
      terms of low cost, low energy consumption, and low mechanical technology is
      highly desirable. The current review presents pros and cons of the natural
      treatment systems, their performance, and recent developments to use them in the
      treatment of various types of wastewaters. Fast population growth and economic
      pressure in some developing countries compel the implementation of principles of
      natural treatment to protect natural environment. The employment of these
      principles for waste treatment not only helps in environmental cleanup but also
      conserves biological communities. The systems particularly suit developing
      countries of the world. We reviewed information on constructed wetlands,
      vermicomposting, role of mangroves, land treatment systems, soil-aquifer
      treatment, and finally aquatic systems for waste treatment. Economic cost and
      energy requirements to operate various kinds of natural treatment systems were
      also reviewed. 

PMID- 23878820
TI  - Factors affecting graft survival among patients receiving kidneys from live
      donors: a single-center experience.
AB  - INTRODUCTION: The aim of this report is to study the graft and patient survival
      in a large cohort of recipients with an analysis of factors that may affect the
      final outcomes. METHODS: Between March 1976 and March 2008, 1967 consecutive live
      donor renal transplants were carried out. Various variables that may have an
      impact on patients and/or graft survival were studied in two steps. Initially, a
      univariate analysis was carried out. Thereafter, significant variables were
      embedded in a stepwise regression analysis. RESULTS: The overall graft survival
      was 86.7% and 65.5%, at 5 and 10 years, respectively. The projected half-life for
      grafts was 17.5 years and for patients was 22 years. Five factors had an
      independent negative impact on graft survival: donor's age, genetic
      considerations, the type of primary immunosuppression, number of acute rejection
      episodes, and total steroid dose during the first 3 months after transplantation.
      CONCLUSIONS: Despite refinements in tissue matching techniques and improvements
      in immunosuppression protocols, an important proportion of grafts is still lost
      following living donor kidney transplantation, presumably due to chronic
      allograft nephropathy.

PMID- 23878821
TI  - Animal models of diabetes and metabolic disease.

PMID- 23878823
TI  - Chronic vascular complications in diabetes.

PMID- 23878822
TI  - Mild diabetes models and their maternal-fetal repercussions.
AB  - The presence of diabetes in pregnancy leads to hormonal and metabolic changes
      making inappropriate intrauterine environment, favoring the onset of maternal and
      fetal complications. Human studies that explore mechanisms responsible for
      changes caused by diabetes are limited not only for ethical reasons but also by
      the many uncontrollable variables. Thus, there is a need to develop appropriate
      experimental models. The diabetes induced in laboratory animals can be performed
      by different methods depending on dose, route of administration, and the strain
      and age of animal used. Many of these studies are carried out in neonatal period
      or during pregnancy, but the results presented are controversial. So this paper,
      addresses the review about the different models of mild diabetes induction using
      streptozotocin in pregnant rats and their repercussions on the maternal and fetal
      organisms to propose an adequate model for each approached issue. 

PMID- 23878824
TI  - Saliva and wound healing.
AB  - Wounds in the oral cavity heal faster and with less scarring than wounds in other
      parts of the body. One of the factors implicated in this phenomenon is the
      presence of saliva, which promotes the healing of oral wounds in several ways.
      Saliva creates a humid environment, which improves the survival and functioning
      of inflammatory cells that are crucial for wound healing. Furthermore, saliva
      contains a variety of proteins that play a role in the various stages of the
      intraoral wound healing. Tissue factor, present in salivary exosomes, accelerates
      the clotting of blood dramatically. The subsequent proliferation of epithelial
      cells is promoted by growth factors in saliva, especially epidermal growth
      factor. The importance of secretory leucocyte protease inhibitor is demonstrated
      by the observation that in the absence of this salivary protein, oral wound
      healing is considerably delayed. Members of the salivary histatin family promote
      wound closure in vitro by enhancing cell spreading and cell migration. Cell
      proliferation is not enhanced by histatin. Cyclization of histatin increased its
      biological activity approximately 1,000-fold compared to linear histatin. These
      studies suggest that histatins could potentially be used for the development of
      new wound healing medications. 

PMID- 23878825
TI  - Tight junctions and paracellular fluid and ion transport in salivary glands.
AB  - Primary saliva is formed by salivary epithelial endpieces through two pathways,
      the transcellular and the paracellular pathways. While the mechanisms of ion
      transport through the transcellular pathway have been well studied, our
      understanding of fluid and electrolyte transport through the paracellular pathway
      remains rudimentary. Increasing evidence indicates that the tight junction (TJ)
      proteins form and regulate the paracellular pathway, although other intercellular
      junctions are probably involved. The structure of the TJ is complex and has not
      been well characterised. A functioning TJ is formed by multiple proteins,
      including membrane, cytoplasmic scaffolding, and signalling proteins.
      Paracellular fluid and electrolyte flow is mediated by high-capacity, charge- and
      size-restrictive small pores with a radius of 4 to 6 A, whereas macromolecules
      pass through low-capacity, nonrestrictive large pores. Although the
      characteristics of these pores need to be further delineated, it is clear that
      they are under the regulation of the autonomic nervous system, endocrine,
      paracrine and autocrine systems, and various pathological factors. To date, the
      majority of the evidence for paracellular fluid and ion transport is accumulated
      from the studies using various epithelia other than salivary glands. Further
      investigations to explore the structure, function, and regulation of the
      paracellular pathway in salivary epithelia are needed to better understand the
      mechanism of saliva secretion. 

PMID- 23878826
TI  - Apical and root canal space sealing abilities of resin and glass ionomer-based
      root canal obturation systems.
AB  - OBJECTIVE: To investigate the apical sealing ability of glass ionomer and resin
      based root canal obturation systems in comparison to a conventional vertical
      compaction of warm guttapercha. METHODS: Forty-five extracted human teeth were
      randomly assigned into 3 groups of 15 each: a resin-based (EndoRez), a glass
      ionomer-based (Activ GP), and a conventional gutta-percha plus pulp sealer
      obturation system (GP/EWT). Apical and root canal space sealing abilities were
      assessed on five cross-sections 1.0 mm apart starting from the apex. Cross
      section images were analysed using a focus-variation 3D scanning microscope and
      unsealed space was calculated as the percentage of total root canal space
      occupied by voids and debris. RESULTS: EndoRez had significantly higher rate of
      apical leakage and deeper dye penetration as compared to GP/EWT and Activ GP.
      EndoRez group had also more voids and debris (22.5%) in the root canal spaces as
      compared to GP/EWT (10.5%) and Activ GP (10.8%). Apical leakages occurred not
      only along the root canal walls, but also along the gutta-percha cones with
      EndoRez as a result of significant polymerisation shrinkage of the resin sealer.
      CONCLUSION: Resin-based EndoRez did not form an adequate apical seal of filled
      root canals. Glass ionomer-based Activ GP was comparable to a vertical compaction
      of warm guttapercha plus EWT sealer in sealing root canal spaces.

PMID- 23878827
TI  - Relation between handling characteristics and application time of four photo
      polymerized resin composites.
AB  - OBJECTIVE: To investigate the relation between handling characteristics and
      application time of four composite materials with subjectively different
      viscosities. METHODS: Eight experienced faculty members placed one Class II and
      one Class IV restoration in a random sequence into pre-prepared plastic teeth
      mounted on a typodont model, each using 4 types of composites (Herculite Precis
      (M1), Kerr; Tertic N-Ceram (M2), Ivoclar Vivadent; Filtek Z350 (M3), 3M-ESPE;
      Charisma Opal (M4), HareausKulzer), resulting in a total of 64 restorations. The
      application process was filmed with a high definition video camera. Two
      evaluators watched the recordings in a random sequence as well, timed the
      composite application and wrote down their observations, which were dichotimised
      into positive and negative ones. Application times were analysed with a two-way
      Kruskal Wallis test (time x dentist) and the observation data were analysed with
      a chi-square test (P < 0.05). RESULTS: Materials did not differ in their
      application time (P > 0.05). The mean application time was 12 1/4 minutes for the
      Class II and 9 3/4 minutes for Class IV restorations. However, there were
      statistically significant differences between the dentists in terms of
      application time. The observation data showed no significant difference between
      Class II and Class IV restorations but there were significant material
      differences (P < 0.05). M2 yielded 6% negative observations, while the other
      materials were between 35% and 38%. CONCLUSION: There was no association between
      the handling characteristics of the tested composite resins and the speed of
      application. However, one of the tested materials (M2) showed significantly less
      problems in the application process.

PMID- 23878829
TI  - Ghost cell differentiation and calcification in ameloblastic fibroma.
AB  - Ghost cell differentiation within an ameloblastic fibroma is extremely rare. The
      ghost cells found in an ameloblastic fibroma in previously reported cases were
      all associated with a typical calcifying odontogenic cyst. Here, we report a case
      of an ameloblastic fibroma with focal ghost cells and calcifications in some
      neoplastic epithelial islands, but without other histologic manifestations
      consistent with a calcifying odontogenic cyst. The patient was a 13-year-old
      Chinese boy who presented with a bony-hard swelling in the posterior mandibular
      region over a 6-month period. Radiographs showed a well-defined multilocular
      radiolucency associated with an unerupted tooth. The lesion was mostly cystic
      solid and comprised of odontogenic epithelial strands, islands and myxoid
      ectomesenchymal component microscopically. Small groups of ghost cells and
      calcification were noted in the epithelial islands. 

PMID- 23878828
TI  - Genotypic diversity and virulence traits of streptococcus sobrinus isolated from
      caries-free children and children suffering severe early childhood caries.
AB  - OBJECTIVE: To evaluate the genotypic diversity and some virulence traits of
      Streptococcus sobrinus (S. sobrinus) isolated from caries-free children and
      children suffering severe early childhood caries (SECC). METHODS: S. sobrinus
      isolated from stimulated whole saliva samples of 91 caries-free children and 87
      SECC children were subcultured, identified by polymerase chain reaction and
      genotyped by arbitrarily primed polymerase chain reaction. Polysaccharide
      synthesis ability, acidogenicity, aciduricity and the adherence ability of these
      S. sobrinus isolates were measured. RESULTS: The frequency of S. sobrinus
      detection was 18.39% (16/87) in SECC children, which was significantly higher
      than that (3.30%, 3/91) in caries-free children. One to three different genotypes
      of S. sobrinus were detected in each SECC child. Only one genotype was colonised
      in each caries-free child. In SECC children, the production of water-insoluble
      glucan (WIG) was positively correlated with the ability of S. sobrinus adhering
      to a glass surface. CONCLUSION: The presence of S. sobrinus could be a risk
      factor for high caries activity in severe early childhood caries. The multi
      genotypes could be related to different caries suceptibility. Water-insoluble
      glucan plays an important role in the adherence and accumulation of S. sobrinus
      on tooth surfaces.

PMID- 23878830
TI  - Endodontic treatments of mandibular first molar with middle mesial canal: two
      case reports.
AB  - The mandibular first molars mostly have two mesial canals. In this report, two
      cases of mandibular first molars with three mesial canals are presented. The
      middle mesial canal was detected under endodontic microscope and further
      confirmed by cone-beam computed tomography and angled radiography, respectively.
      The purpose of this paper was to highlight the possibility of an aberrant root
      canal in a mandibular first molar and to help reduce the failure rates of the
      dental pulp treatment of the mandibular first molar. 

PMID- 23878831
TI  - Platelet-rich fibrin in treatment of periapical lesions: a novel therapeutic
      option.
AB  - In the present case of a 35-year old patient, platelet-rich fibrin, which is an
      autologous platelet concentrate, was used to fill the osseous defect following
      surgery. The case was assessed both clinically and radiographically for a period
      of 9 months. 

PMID- 23878832
TI  - Does rinsing following particle deposition methods have a negative effect on
      adhesion to titanium?
AB  - PURPOSE: This study evaluated whether air blasting or rinsing particle remnants
      with water would impair adhesion of resin composite to metal. MATERIALS AND
      METHODS: Commercially pure titanium plates (1 mm x 25 mm x 50 mm) were wet
      polished down to 1200-grit silicone carbide abrasive and ultrasonically cleaned.
      They were then embedded in auto-polymerizing acrylic with the bonding surfaces
      exposed. Specimens were randomly assigned to one of the following particle
      deposition protocols (N = 60, n = 10 per group): group 1: particle deposition
      with aluminum trioxide (50 um Al2O3) (AL) + air blasting + silane (ESPE-Sil);
      group 2: particle deposition with 30 um SiO2 (CoJet) (CSC) + air blasting +
      silane; group 3: particle deposition with Rocatec Pre 110 um Al2O3+Rocatec Plus
      110 um SiO2 (LSC) + air blasting + silane. In groups 4 (AL-W), 5 (CSC-W) and 6
      (LSC-W), the same protocols were used, but instead of air blasting only, particle
      deposited specimen surfaces were rinsed with water and air blasted. Adhesive
      resin (VisioBond) was applied and resin composite (Quadrant Posterior, Cavex) was
      bonded using polyethylene molds and photopolymerized. The specimens were then
      submitted to thermocycling (6000 cycles, 5 degrees C-55 degrees C, dwell time: 30
      s, transfer time: 5 s). Pre-test failures during thermocycling were assigned a
      value of 0 MPa. Failure modes were identified using an optical microscope. SEM
      images of particles were obtained. Bond strength data (MPa) were statistically
      analyzed using two-way ANOVA and Tukey's post-hoc tests (a = 0.05). RESULTS:
      Particle type significantly affected the bond results (p < 0.001). AL groups
      presented significantly lower results (air blasting: 4.3 +/- 3.3, rinsing: 11.8
      +/- 6.5) compared to those of CSC (air blasting: 27.7 +/- 6.6, rinsing: 30.4 +/-
      9.3) and LSC (air blasting: 31.4 +/- 8.7, rinsing: 28.7 +/- 7.0). AL groups
      presented 5 spontaneous debondings during thermocycling in the air-blasted group.
      Rinsing with water as opposed to air blasting only did not decrease the results
      with any of the particle types (p > 0.05). While AL groups showed exclusively
      adhesive failure between the resin composite and the substrate, the incidence of
      cohesive failures in the composite was more frequent in groups CSC and LSC after
      either air blasting or rinsing. SEM images of particles showed sharp morphology
      of the particles in AL compared to CSC and LSC. CONCLUSION: Rinsing and air
      blasting following particle deposition methods did not impair adhesion of resin
      composite to titanium. Particle deposition with silica particles provided better
      adhesion of resin composite to this substrate compared to the use of alumina
      particles.

PMID- 23878833
TI  - Microshear bond strength and finite element analysis of resin composite adhesion
      to press-on-metal ceramic for repair actions after various conditioning methods.
AB  - PURPOSE: This study evaluated the repair bond strength of differently surface
      conditioned press-on-metal ceramic to repair composites and determined the
      location of the accumulated stresses by finite element analysis. MATERIALS AND
      METHODS: Press-on-metal ceramic disks (IPS InLine PoM, Ivoclar Vivadent) (N = 45,
      diameter: 3 mm, height: 2 mm) were randomly divided into 3 groups (n = 15 per
      group) and conditioned with one of the following methods: 9.5% hydrofluoric acid
      (HF) (Porcelain etch), tribochemical silica coating (TS) (CoJet), and an
      unconditioned group acted as the control (C). Each group was divided into three
      subgroups depending on the repair composite resins: a) Arabesk Top (V, a
      microhybrid; VOCO), b) Filtek Z250 (F, a hybrid;3M ESPE); c) Tetric EvoCeram (T,
      a nanohybrid; Ivoclar Vivadent) (n = 5 per subgroup). Repair composites disks
      (diameter: 1 mm, height: 1 mm) were photopolymerized on each ceramic block.
      Microshear bond strength (MSB) tests were performed (1 mm/min) and the obtained
      data were statistically analyzed using 2-way ANOVA and Tukey's post-hoc test
      (alpha = 0.05). Failure types were analyzed under SEM. Vickers indentation
      hardness, Young's modulus, and finite element analysis (FEA) were performed
      complementary to MSB tests to determine stress accumulation areas. RESULTS: MSB
      results were significantly affected by the surface conditioning methods (p =
      0.0001), whereas the repair composite types did not show a significant effect (p
      = 0.108). The interaction terms between the repair composite and surface
      conditioning method were also statistically significant (p = 0.0001). The lowest
      MSB values (MPa +/- SD) were obtained in the control group (V = 4 +/- 0.8; F =
      3.9 +/- 0.7; T = 4.1 +/- 0.7) (p < 0.05). While the group treated with T
      composite resulted in significantly lower MSB values for the HF group (T= 4.1 +/-
      0.8) compared to those of other composites (V = 8.1 +/- 2.6; F = 7.6 +/- 2.2) (p
      < 0.05), there were no significant differences when TS was used as a conditioning
      method (V = 5 +/- 1.7; F = 4.7 +/- 1; T = 6.2 +/- 0.8) (p > 0.05). The control
      group presented exclusively adhesive failures. Cohesive failures in composite
      followed by mixed failure types were more common in HF and TS conditioned groups.
      Elasticity modulus of the composites were 22.9, 12.09, and 10.41 GPa for F, T,
      and V, respectively. Vickers hardness of the composites were 223, 232, and 375 HV
      for V, T, and F, respectively. Von Mises stresses in the FEA analysis for the V
      and T composites spread over a large area due to the low elastic modulus of the
      composite, whereas the F composite material accumulated more stresses at the
      bonded interface. CONCLUSION: Press-on-metal ceramic could best be repaired using
      tribochemical silica coating followed by silanization, regardless of the repair
      composite type in combination with their corresponding adhesive resins, providing
      that no cohesive ceramic failure was observed.

PMID- 23878834
TI  - Perception and attitude about systemic health and periodontal disease among
      dentistry undergraduates.
AB  - PURPOSE: To evaluate the perceptions held by dentistry undergraduates about the
      relationship between general health and periodontal disease. In addition, student
      knowledge about treatment of patients with systemic disorders was also examined.
      MATERIALS AND METHODS: Participants were all undergraduates in the last year of
      dental school from three different universities (N = 253). Inclusion criteria
      were students enrolled in their last year of the dental curriculum and who agreed
      to participate in the research. After the participants filled out a structured
      questionnaire, the results were analysed using Epi Info 3.5.1 software and the
      chi-square, Friedman and Wilcoxon tests. RESULTS: The majority of participants
      recognised the relationship between periodontal and cardiac disease and diabetes
      mellitus. However, only half of the participants were aware of the relationship
      between periodontal disease and stroke (50.5%). In relation to caring for
      patients with systemic diseases, 61.4% of students surveyed did not know the
      blood glucose level that characterises a hypoglycemic status. The majority of
      participants (61.8%) stated the importance of evaluating vital signs prior to
      dental treatment. However, only 13.3% of the participants included temperature
      and respiratory rate as vital signs. CONCLUSION: The perception and attitude of
      undergraduates about the items on the questionnaire were deficient. Thus, a more
      holistic view of the patient is warranted within dental education, promoting
      health and quality of life.

PMID- 23878835
TI  - Validation of a Romanian version of the short form of the oral health impact
      profile (OHIP-14) for use in an urban adult population.
AB  - PURPOSE: To obtain a valid Romanian version of the OHIP-14 for use among Romanian
      adults, either in Romania or abroad. MATERIALS AND METHODS: The Romanian version
      of the OHIP-14 was obtained through the back translation technique and pre-tested
      in a pilot study. Subsequently, it was self-administered to 187 adults who also
      underwent a clinical examination. Cronbach alpha was used to check the internal
      consistency and reliability analysis and validity tests were used to determine
      the psychometric properties of the questionnaire. RESULTS: The Cronbach alpha
      coefficient obtained was 0.88. Inter-item correlation coefficients were between
      0.01 and 0.74; item-total correlation values ranged between 0.25 and 0.77. There
      were statistically significant associations (p <= 0.001) between the respondents'
      self-perceived oral health (r = 0.41), the dental treatment need (r = 0.35) and
      the mean of the OHIP-14 total scores. Similar statistically significant
      associations (p <= 0.001) existed between the OHIP-14 total scores mean and the
      clinical data - the number of decayed (D) and of missing (M) teeth and the
      prosthetic treatment need - proving the construct validity of the questionnaire.
      The subscales 'physical pain' and 'psychological disability' have the most
      important impact on the overall OHIP-14 score. The subscales 'social disability'
      and 'handicap' seem to make the least contribution to the overall OHIP-14 score.
      CONCLUSION: The Romanian version of the OHIP-14 is a valid and reliable
      questionnaire that can be used in future studies.

PMID- 23878836
TI  - Association of periodontal disease with self-reported systemic disorders in
      Greece.
AB  - PURPOSE: The aim of this retrospective investigation was to examine the
      occurrence of periodontal disease in patients referred to a specialist clinic for
      neurosurgery and to explore possible associations between common systemic
      disorders and periodontal disease in an adult population in Greece. MATERIALS AND
      METHODS: The study sample consisted of 1,652 individuals, 760 males and 892
      females, aged 40 to 68 years, with a mean age of 57.3 +/- 4.7 years. Data were
      collected by means of an oral clinical examination and a self-administered
      questionnaire. Statistical analysis of questionnaire items was performed by using
      a multiple linear regression analysis model in order to estimate correlations
      between systemic disorders as independent variables, and the relative frequency
      of periodontal pockets of 5 mm or more and the frequency of clinical attachment
      loss of 6 mm or more as dependent variables. RESULTS: The relative frequencies of
      periodontal pockets >= 5.0 mm and clinical attachment loss >= 6.0 mm as expressed
      in terms of mean values were 76% and 70.2%, respectively, for individuals who
      suffer from cardiovascular disease and 62.3% and 52.9% respectively, for those
      who suffer from respiratory disease. The depth of periodontal pockets was
      significantly and positively correlated to the presence of respiratory diseases
      (P = 0.0001) and diabetes mellitus (P = 0.0001) after adjustment for age, gender
      and smoking, whereas clinical attachment loss was significantly and positively
      correlated to the presence of diabetes mellitus (P = 0.0001) and cardiovascular
      diseases (P = 0.037). CONCLUSION: Based on the clinical criteria for established
      periodontitis, the current study supports associations between periodontal
      disease and systemic disorders such as diabetes mellitus, cardiovascular and
      respiratory diseases.

PMID- 23878837
TI  - Comparison of normative methods and the sociodental approach to assessing
      orthodontic treatment needs in 12-year-old schoolchildren.
AB  - PURPOSE: To compare normative methods of orthodontic treatment need with the
      sociodental approach in 12-year-old students and correlate the normative measures
      of malocclusion with the impact of oral health on daily activities. MATERIALS AND
      METHODS: A cross-sectional study of 201 12-year-old students was conducted in the
      city of Manaus, Brazil. The normative orthodontic treatment need was determined
      by oral clinical examination using two occlusal indices, the Index of Orthodontic
      Treatment Need (IOTN), comprising the Dental Health Component (DHC) and Aesthetic
      Component (AC ), and the Dental Aesthetic Index (DAI). The sociodental approach
      combined normative measures (IOTN and DAI), the impact of malocclusion on daily
      activities (Child-Oral Impacts on Daily Performances index, Child-OIDP) and
      propensity- related orthodontic treatment assessment. The normative method and
      the sociodental approach of orthodontic treatment needs assessment were compared
      using the McNemar test. The association between the impact of malocclusion on
      daily activities and normative orthodontic need was tested using chi2 and Kruskal
      Wallis tests. RESULTS: The frequency of individuals with normative need according
      to IOTN/DHC (24.9%) and DAI (42.3%) was statistically higher when compared with
      the sociodental approach (<= 4.5%) (P < 0.001). The sociodental approach provided
      different results using IOTN/DHC (1.5%) and DAI (4.5%) (P < 0.001). The magnitude
      of normative need was associated with the impact of malocclusion on children's
      daily activities. CONCLUSION: Substantial reductions in normative need estimates
      for orthodontic treatment were observed using the sociodental approach. The
      sociodental approach for orthodontic treatment needs can optimise the use of
      resources in oral health services.

PMID- 23878838
TI  - Salivary thiocyanate: a biochemical indicator of cigarette smoking in
      adolescents.
AB  - PURPOSE: Saliva is considered to be critical for the maintenance of healthy oral
      mucosa, and oral fluids provide an easily available, non-invasive medium for the
      diagnosis of a wide range of diseases and clinical situations. The purpose of
      this study was to estimate the thiocyanate (SCN) level in saliva of cigarette
      smokers and compare it with that of nonsmokers. MATERIALS AND METHODS: The
      present study comprised 100 subjects, of which 50 had a habit of tobacco smoking.
      The other 50 neither smoked nor chewed tobacco and comprised the healthy control
      group. The age and sex (all males) of both groups of subjects were matched. All
      the patients were in the age group of 25 to 40 years. The group of smokers was
      divided into subgroups according to duration and frequency of smoking. Duration
      group 1: smoking for a period of 4-7 years; duration group 2: smoking for a
      period of 8-15 years; duration group 3: chronic smokers, smoking for a period of
      more than 15 years. Frequency group 1: patients smoked half pack of cigarettes,
      i.e. 4-6 per day; frequency group 2: patients smoked one pack of cigarettes, i.e.
      7-11 per day; frequency group 3: patients smoked more than one pack, i.e. >11,
      per day. Saliva was collected by the spitting method. Unstimulated whole saliva
      was refrigerated at 4 degrees C and processed within 24 h. The estimation of
      thiocyanate in saliva was done according to Densen et al (1967). RESULTS: The
      present study clearly indicates a significant increase in salivary thiocyanate
      level in tobacco smokers as compared to nonsmokers (P < 0.0001). Comparing
      salivary SCN in different duration groups, the salivary SCN level was
      significantly lower in group 1 vs groups 2 and 3, with P < 0.0001. In terms of
      smoking frequency, the salivary SCN level was significantly lower in group 1 vs
      group 3, P < 0.0001. It is also evident that there was an increase in salivary
      thiocyanate levels with increased duration and frequency, thus showing a positive
      correlation between them. CONCLUSION: The findings of this study suggest that
      salivary thiocyanate can be used as a safe and acceptable prevalence measurement
      for cigarette smoking behaviour.

PMID- 23878839
TI  - Remineralisation of carious lesions and fluoride uptake by enamel exposed to
      various fluoride dentifrices in vitro.
AB  - PURPOSE: To evaluate the relative performance of fluoride (F) dentifrices to
      promote remineralisation and enamel F acquisition using an in vitro pH-cycling
      model. Enamel surface morphology was investigated. MATERIALS AND METHODS: Thirty
      six white spot lesions and 36 sound enamel sections from extracted premolars and
      molars were randomly assigned to 8 experimental groups and a placebo group. Eight
      commercially available brands of Fdentifrices were used: A. 0.8%
      monofluorophospate (MFP)-silica; B. 0.8% MFP-calcium carbonate and calcium
      phosphate; C. 0.8% MFP-calcium carbonate and calcium phosphate; D. 0.76% MFP
      aluminium hydroxide; E. 0.24% sodium fluoride (NaF)-silica and sodium
      pyrophosphate; F. 0.24% NaF-silica and sodium pyrophosphate; G. 0.76% MFP and
      0.10% NaF-dicalcium phosphate and sodium pyrophosphate (1450 ppm F); H. 0.76% MFP
      and 0.33% NaF-silica (2500 ppm F). The placebo (I) contained non-fluoridated
      silica. The cycling regimen comprised the following: three 2-min and one 4-min
      daily treatments with dentifrice slurries, rinsed with water and stored in fresh
      whole saliva at 37 degrees C until the next experimental day, when specimens were
      activated in acid buffer solutions prior to each dentifrice treatment. This pH
      cycling continued for 21 consecutive days. Lesion depths and size were measured
      using a polarising microscope and enamel F uptake was determined using the acid
      etch biopsy technique. The morphology of enamel surfaces was examined using
      scanning electron microscopy. The data were statistically analysed using
      Student's t-test, analysis of variance (ANOVA) and Pearson's correlation
      coefficient (r). RESULTS: All tested fluoride dentifrices significantly enhanced
      remineralisation by reducing the lesion depths from 6.4 to 17.1 um and lesion
      sizes by 10% to 34% relative to the pre-cycling measurements. Overall, the degree
      of remineralisation was as follows: NaF-silica-pyrophosphate dentifrices (1000
      ppm F) averaged 41%; NaF/MFP-silica (1500/1000 ppm F) 38%; MFP/NaF-dicalcium
      phosphate (1000/450 ppm F) 30%; MFP dentifrices (1000 ppm F) ranged from 15 to
      23%. Enamel F uptake by NaF and NaF/MFP was significantly greater than MFP
      dentifrices (P < 0.05 to P < 0.001), with the area under the depth curve being
      2.4 and 2.2 times greater, respectively. At all enamel depths, fluoride
      dentifrices significantly increased F concentrations relative to the control (P <
      0.001). A strong correlation was found between ionic F levels in dentifrices and
      their efficacy. Dentifrices produced different enamel surface morphologies.
      CONCLUSIONS: The present study demonstrates that commercially available
      dentifrices vary in their degree of effectiveness and mode of action depending on
      formulations.

PMID- 23878840
TI  - Current status and trends in oral health in community dwelling older adults: a
      global perspective.
AB  - PURPOSE: To record the available current national and regional data on the oral
      health of community-dwelling (living in their own homes, not institutionalised)
      older people globally and discuss the future trends considering existing dangers
      and opportunities. MATERIALS AND METHODS: A literature search on tooth loss,
      dental decay and periodontal disease in the elderly was performed using available
      databases and electronic sources. RESULTS: The findings revealed that the updated
      national data are scarce in many parts of the world, particularly in Africa, Asia
      and South America, and direct comparisons are not always possible due to
      methodological variations. The available information may indicate that dental
      disease in older adults worldwide is more prevalent compared to younger age
      groups, with significant variation between countries and regions. Tooth loss is
      currently more common in the developed countries, while dental decay and
      periodontal disease are more widespread globally. There are important threats for
      further deterioration of the oral status among older adults in many developed and
      less developed areas due to existing sociodemographic and economic risk factors.
      CONCLUSION: National studies should be undertaken to record the specific oral
      problems of the elderly in each area. It is also necessary to develop
      gerodontology study programmes globally at the undergraduate, postgraduate and
      continuing education levels which will enhance dentists' knowledge, skills and
      attitudes towards oral care in the older population, and will promote
      opportunities for further research and development of relevant policies.

PMID- 23878841
TI  - Salivary and serum B-cell activating factor (BAFF) levels after
      hydroxychloroquine treatment in primary Sjogren's syndrome.
AB  - PURPOSE: Some evidence implicates a role of hydroxychloroquine (HQ) in the
      management of Sjogren's syndrome. This study evaluated the effect of HQ on saliva
      B-cell activating factor (BAFF) levels as well as health related quality of life
      (QoL) in patients with primary Sjogren's syndrome (pSS). MATERIALS AND METHODS:
      Ten pSS patients who had been treated with HQ for at least 2 years and 15 healthy
      controls (HC) were included in the study. First, HQ was withdrawn for 12 weeks,
      then baseline evaluation was performed. Subsequently, HQ was restarted and
      further evaluations were carried out after 12 and 24 weeks of HQ treatment. Oral
      infection foci were eliminated by dental and periodontal treatments in both
      groups before enrollment. BAFF levels were evaluated with ELISA in serum and
      unstimulated mixed saliva. Salivary flow rates of patients and the control group
      were measured as well. Oral health quality of life (QoL) was evaluated by an oral
      health impact profile-14 (OHIP-14) questionnaire. RESULTS: Salivary BAFF levels
      (median: 12.39 ng/ml) were significantly decreased by using HQ both at 12 (2.78
      ng/ml, P = 0.008) and 24 weeks (0.54 ng/ml, P = 0.011). Similarly, decreases in
      serum BAFF levels (5.23 ng/ml) were seen at 12 and 24 weeks after HQ treatment
      (2.18 ng/ml, P = 0.008 and 0.0 ng/ml, P = 0.012, respectively). Serum and
      salivary BAFF levels were significantly lower in healthy controls (0.37 ng/ml and
      0.0 ng/ml, resp.) compared to those of pSS before HQ therapy (P = 0.006 and P =
      0.001, resp.). Unstimulated salivary flows were similar in patients treated with
      HQ after 12 (0.38 ml/min) and 24 weeks (0.50 ml/min) (P = 0.51) but higher than
      the patients' rate at baseline (0.04 ml/min) (P = 0.008). CONCLUSION: Salivary
      and serum BAFF levels were lowered in patients with pSS when treated with HQ. In
      addition, decreased disease activity and increased salivary flows can be achieved
      with HQ in pSS patients.

PMID- 23878842
TI  - Validation of a Hebrew version of the child-OIDP index, an oral health-related
      quality of life measure for children.
AB  - PURPOSE: Sociodental indicators assess to what extent oral conditions interfere
      with normal social functions and alter behaviour such as attending work or
      school, parenting or home chores. The child OIDP (oral impact on daily
      performance), a sociodental indicator developed by Adulyan and Sheiham, is easy
      to apply and has a scoring system that quantifies the effect both by extent and
      frequency. The purpose of this study was to adapt the child OIDP into Hebrew and
      evaluate its validity and reliability. MATERIALS AND METHODS: The questionnaire
      was translated from English into Hebrew and back again. After receiving
      permission from parents and from the children attending the consultation clinic
      of the Department of Children's Dentistry at the Hebrew University-Hadassah
      Dental School, we examined their dental condition and asked them to answer the
      questions. According to the results, we analysed the reliability and the validity
      of the questionnaire. RESULTS: 179 children aged 6-11 years answered the
      questions. 88.8% of the children that attended the dental clinic experienced an
      oral or dental problem and 52.5% of them experienced interference in at least one
      of 8 everyday activities because of oral or dental problems in the 3 months prior
      to the interview. The OIDP was found valid in the aspects of Face, Content and
      Construct validity and with good internal reliability. CONCLUSIONS: The validity
      and the reliability of the Hebrew child OIDP found in the present study enables
      its use in future studies to assess the impact of oral health on children's
      quality of life.

PMID- 23878843
TI  - Barriers to restorative care as perceived by dentists in Nigeria.
AB  - PURPOSE: To identify the barriers to restorative care as perceived by dentists
      working in urban and semi-urban dental hospitals in Nigeria. MATERIALS AND
      METHODS: The study was cross sectional and the sample consisted of 189 of 280
      dentists who consented to, filled out and returned the questionnaire mailed to
      them. The questionnaire consisted of fifteen itemed statements and the
      respondents were asked to what extent they agreed or disagreed with each item on
      a four-point Likert scale; 'not at all', 'slight extent', 'some extent' and
      'great extent'. Five barrier factors were extracted from the questionnaire. These
      were 'beliefs of patients', 'knowledge of patients', 'equipment/materials',
      'attitude' and 'motivation of practitioner'. Two questions were not grouped with
      the barrier factors: 'dentistry is being looked down on by administration' and
      'patients prefer extraction to filling'. RESULTS: The barrier factor 'attitude of
      patients' had the highest score (mean = 3.73), followed by the 'knowledge of
      patients' (mean = 3.27). The barrier factor 'belief of patients' had the lowest
      score (mean = 2.43). CONCLUSION: Within the limitations of the study, the barrier
      factor 'attitude of patients' was the most important barrier to restorative care
      as perceived by dentists working in urban and semi-urban regions of Nigeria.

PMID- 23878844
TI  - Localized periodontal defect associated with unusual furcation involvement on a
      mandibular incisor.
AB  - A localized periodontal defect associated with an unusual furcation on a
      mandibular central incisor and its treatment sequences are presented. A 54-year
      old woman presented with a persistent localized periodontal defect, which was not
      responsive to nonsurgical periodontal therapy. An exploratory surgery revealed
      complete through and through furcation involvement on the right mandibular
      central incisor, resulting in a three-walled infrabony defect. Following thorough
      mechanical debridement and root planing, the infrabony aspect of the defect was
      grafted with freeze-dried bone allograft combined with the recombinant human
      platelet-derived growth factor-BB. The flaps were positioned to enable patient's
      home care and professional dental cleaning. Follow-up examination revealed
      uneventful healing and resolution of the infrabony periodontal defect. Clinicians
      should be aware of this unusual condition and consider it as a potential etiology
      when dealing with a persistent localized periodontal defect in the mandibular
      anterior sextant, which may not respond to the conventional nonsurgical
      periodontal therapy. Eliminating the active disease as well as enabling careful
      maintenance and oral hygiene may prevent further deterioration and result in a
      stable long-term outcome preserving the compromised tooth. 

PMID- 23878845
TI  - Randomized clinical evaluation of the effect of chlorhexidine on postoperative
      sensitivity of posterior composite resin restorations.
AB  - OBJECTIVES: Evaluation of postoperative sensitivity in posterior teeth restored
      with etchand- rinse adhesive and composite resin after application of 2%
      chlorhexidine solution. METHOD AND MATERIALS: Thirty participants with similar
      dental caries on both sides of the jaws were selected. After cavity preparation,
      each tooth was randomized to one of the following restoration methods. Teeth in
      the control group were restored using etch-and-rinse resin adhesive (Single Bond,
      3M ESPE) and universal microhybrid composite resin (Filtek Z250, 3M ESPE).
      Restoration of teeth in the experimental group was similar to the control group
      except that 2% chlorhexidine solution (Concepsis, Ultradent) was applied on the
      etched dentin for 60 seconds. Subjects were recalled for evaluation of
      postoperative sensitivity at 1 day, 1 week, 1 month, and 6 months. Data were
      analyzed by Fisher exact test (alpha = .05). RESULTS: The experimental group
      showed significantly less postoperative sensitivity (8 teeth) compared with the
      control group (20 teeth) at the 1-day recall (P < .05; Fisher exact test).
      Conventional restorations were comparable to teeth treated with chlorhexidine at
      other recall times (P > .05). CONCLUSION: Chlorhexidine significantly decreased
      immediate postoperative sensitivity of posterior teeth restored by composite
      resin.

PMID- 23878846
TI  - Arginine-containing toothpastes for dentin hypersensitivity: systematic review
      and meta-analysis.
AB  - OBJECTIVE: Arginine-containing toothpastes are a promising new treatment for
      dentin hypersensitivity (DH), which afflicts a considerable number of patients.
      However, there have to date been only individual studies. We aim to present an
      overview of the clinical evidence in order to determine trends and establish
      firmer conclusions regarding the use of arginine-containing toothpastes for
      management of DH. METHOD AND MATERIALS: A protocol was developed based on the
      Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0),
      including: search strategy, selection criteria, data extraction, and risk of bias
      assessment. We searched electronic databases (up to October 2012) without
      language limitation, and reference lists of relevant papers for randomized
      controlled trials that assessed the efficacy of arginine-containing toothpastes
      for DH treatment. Data extraction and domain-based risk of bias assessment were
      independently performed by two reviewers. The meta-analysis was performed in
      STATA (version 12.0). The GRADE analysis was conducted in GRADE profiler (version
      3.6). RESULTS: Fourteen randomized controlled studies with different risk of bias
      were included in the meta-analysis, all evaluated by tactile and air blast
      assessment. The mean differences and standard deviations for each treatment group
      were pooled for analysis using a random-effect model. We found that arginine
      containing toothpastes had better overall effects in comparison with placebo
      toothpastes (P < .05), potassium salt-containing toothpastes (P < .05), and
      strontium-containing toothpastes (P < .05). The GRADE analysis showed that
      quality of the evidence was moderate when arginine-containing toothpastes were
      compared to placebo and potassium salt-containing toothpastes, and quality of the
      evidence was low with comparison to strontium-containing toothpastes. CONCLUSION:
      Current available clinical evidence suggests that arginine-containing toothpastes
      are associated with the reduction of DH compared to both placebo and positive
      control toothpastes. However, there are limitations to the current studies, and
      more well-designed trials are needed to confirm the efficacy.

PMID- 23878847
TI  - Maintaining space in localized ridge augmentation using guided bone regeneration
      with tenting screw technology.
AB  - Prosthetic guided implant surgery requires adequate ridge dimensions for proper
      implant placement. Various surgical procedures can be used to augment deficient
      alveolar ridges. Studies have examined new bone formation on deficient ridges,
      utilizing numerous surgical techniques and biomaterials. The goal is to develop
      time efficient techniques, which have low morbidity. A crucial factor for
      successful bone grafting procedures is space maintenance. The article discusses
      space maintenance tenting screws, used in conjunction with bone allografts and
      resorbable barrier membranes, to ensure uneventful guided bone regeneration (GBR)
      enabling optimal implant positioning. The technique utilized has been described
      in the literature to treat severely resorbed alveolar ridges and additionally can
      be considered in restoring the vertical and horizontal component of deficient
      extraction sites. Three cases are presented to illustrate the utilization and
      effectiveness of tenting screw technology in the treatment of atrophic extraction
      sockets and for deficient ridges.

PMID- 23878848
TI  - Effect of post diameter and cement thickness on bond strength of fiber posts.
AB  - OBJECTIVE: This study evaluated the effects of different post diameter and
      oversized post spaces on the push-out bond strength of a fiber post to dentin.
      METHOD AND MATERIALS: Fifty extracted human maxillary central incisors and
      canines were divided into five groups and submitted to the push-out test (0.5 mm
      min-1). Groups 1, 2, and 3 were restored using a fiber post size that was
      identical to the drill size (sizes 1, 2, and 3, respectively), and groups 4 and 5
      were both prepared with drill size 3, and restored using the size 2 and 1 fiber
      post, respectively. The fiber posts were cemented using self-adhesive dual
      polymerized resin cement (RelyX Unicem). The data were analyzed using a one-way
      analysis of variance (ANOVA) and the Tukey test. RESULTS: There were no
      significant differences in the mean values for push-out bond strength between
      groups with different post diameters (P > .05). However, the push-out bond
      strengths were significantly different between groups with different cement
      thicknesses, and group 4 yielded the highest bond strength (11.7 +/- 0.4 MPa).
      For all groups, the apical third had the lowest bond strength value (P < .05).
      CONCLUSION: The highest push-out bond strength values were obtained when one
      incremental oversized post space was used. Clinically, fiber post space has to
      provide an optimum cement thickness (around 120 um) for adequate cementation.

PMID- 23878849
TI  - Household laundry detergent as a possible cause of oral lichenoid lesions.
AB  - Oral lichenoid lesions (OLLs) are a diverse group of disorders that may be
      attributed to an autoimmune etiology, underlying systemic disease, or in
      association with an identifiable causative agent, such as a medication, food
      product, or dental material. OLLs commonly present with striae, erythema, and/or
      ulceration on affected oral mucosa and can be symptomatic. The aim of this report
      is to describe a case of OLLs that were believed to be attributed to use of
      household laundry detergent to clean an oral occlusal appliance. 

PMID- 23878850
TI  - Atypical odontalgia: quo vadis?

PMID- 23878852
TI  - Wellcome Trust scheme boosts sustainable health research.

PMID- 23878853
TI  - Glycopeptide targeting of vaccine antigens to dendritic cells.

PMID- 23878854
TI  - India's new food bill sparks debate.

PMID- 23878855
TI  - Targeting poly-d,l-lactide-co-glycolide-based vaccines to skin dendritic cells.

PMID- 23878856
TI  - What's causing England's A&E crisis?

PMID- 23878857
TI  - Conference marks 100 years of Albert Schweitzer's hospital.

PMID- 23878858
TI  - Lipid nanoparticle-based delivery of RNA.

PMID- 23878859
TI  - The shift to personalised and population medicine.

PMID- 23878860
TI  - The benefits of brain mapping.

PMID- 23878861
TI  - Active protection.

PMID- 23878862
TI  - Light show.

PMID- 23878863
TI  - Online learning: how to make a MOOC.

PMID- 23878865
TI  - New features: teaching case studies and mobile journal app.

PMID- 23878864
TI  - Author response.

PMID- 23878866
TI  - Patients and price. HFMA looks at costs, transparency.

PMID- 23878867
TI  - A framework for service learning in physician assistant education that fosters
      cultural competency.

PMID- 23878868
TI  - [Generous regional melanoma metastasis].

PMID- 23878869
TI  - [Effect of transfection of microRNA-146a on expression of tumor necrosis factor-a
      in alveolar macrophages].
AB  - OBJECTIVE: To observe the effect of transfected microRNA-146a (miR-146a) on
      expression of tumor necrosis factor-alpha ( TNF-alpha ) in alveolar macrophages,
      and to analyze its regulatory mechanism in the inflammatory response of alveolar
      macrophages. METHODS: Cy.11113 labeled with 25, 50, 100 nmol/L of Pre-miR",
      respectively, were transfected into rat alveolar macrophages NR8383 cultured in
      vitro. The highest transfection efficiency was selected to he the experimental
      concentration. NR8383 cells were divided into two groups: transfected group was
      tranfected with 50 nmol/L Pre-miR1111 miR-146a precursor, and control group with
      SO nmol/L Cym3 labeled Pre-miR1" as the negative control. The mRNA expression of
      miR-146a of cells was detected hy real-time quantitative reverse transcription
      polymerase chain reaction (RT-qPCR). Then cells were stimulated with
      lipopolysaccharide (LPS, 1 mg/L) for 6 hours. The production of TNF-alpha protein
      in the supernatant of cells was assayed by enzyme-linked immunosorhent assay
      (ELISA) , and the expression of TNF-alpha mRNA of cells was detected hy RT-qPCR.
      RESULTS: Transfection rate was highest in the 50 nmol/L Cy11113 labeled Pre-miR"'
      cells, and it reached 80%. Compared with control group (set at 1), the expression
      of miR-146a increased by (24.55 +/-6.14) folds in transfected alveolar
      marrophages (P<0.01). After the cells were stimulated with LPS, the production of
      TNF-alpha protein (ng/L) in the supernatant of cell was decreased from 616.6 +/-
      42.3 to 211.5 +/- 30.4 (P<0.01), and the expression of TNF-alpha mRNA was
      decreased by (47 +/- 6) % (P<0.05) in transfected alveolar macrophages when
      compared with that of the control. CONCLUSIONS: Transfection alveolar macrophages
      with miR-146a precursors could down-regulate the expression of TNF-alpha. It is
      therefore suggests that up-regulation of miR-146a can inhibit inflammatory
      responses as induced hy LPS, in alveolar macrophages.

PMID- 23878870
TI  - Irrational model. Healthcare economist reveals connection between behavior, care.
      An interview with Douglas Hough. Interview by Jason Saffron.

PMID- 23878871
TI  - A sticky situation: fibrinogen and coronary artery disease.

PMID- 23878872
TI  - Clot Disruption: the role of the D-dimer in testing for deep vein thrombosis.

PMID- 23878873
TI  - [What is our professional identity in nursing?].

PMID- 23878874
TI  - [Endocrine disruptors and metabolic diseases - prevention is essential].

PMID- 23878875
TI  - [A new system for blood glucose self measurement].

PMID- 23878876
TI  - [Application for marketing authorization accepted for the the treatment of adult
      diabetes].

PMID- 23878877
TI  - [Diagnosis and treatment of chronic wound infections].
AB  - The treatment of chronic wounds is slow and difficult and the presence of an
      infection can further delay the healing. Diagnosis of this infection is clinical.
      It must be accompanied by targeted sampling carried out in accordance with a
      specific technique in order to adapt the treatment as best as possible.

PMID- 23878878
TI  - [Body image disturbance, nursing objectives and interventions].
AB  - Faced with a changed body, several nursing care interventions are possible in
      order to restore self-esteem. Relational and personal care techniques or other
      forms of body mediation are all tools which can be used in order to reposition
      the patients at the centre of the care.

PMID- 23878879
TI  - [Breast cancer. Personalized care throughout the illness].

PMID- 23878880
TI  - [Epidemiology and risk factors of breast cancer].
AB  - A major public health issue, breast cancer affects 53000 women each year in
      France. The leading cause of cancer deaths in women, its risk factors are
      numerous and include age, early puberty and/or late menopause, later age at first
      pregnancy as well as a family history of the disease.

PMID- 23878881
TI  - [Physiopathology, diagnosis and treatment of breast cancer].
AB  - The organised screening of breast cancer, the identification of the type of
      lesion and the staging determine the treatment plan for this disease. The most
      common cancer to affect women in France and in Europe, it represents 1/3 of
      cancers in women and 1/4 of all cancers.

PMID- 23878882
TI  - [Family and genetic risk of breast cancer].
AB  - Screening for breast cancer should concern all women at some point in their life.
      In cases of a family history of breast cancer, an oncogenetic consultation may be
      offered. The identification of a genetic predisposition enables specific
      management strategies for the woman to be drawn up.

PMID- 23878883
TI  - [Breast cancer, patients at the heart of the care plan].
AB  - In the Centre region of France, breast cancer is one of the three most common and
      most fatal forms of the disease. Chartres hospitals offer complete care provision
      on a single site and assess the time taken for the appropriate care to be put in
      place. The nurse coordinator plays an essential role in the process.

PMID- 23878884
TI  - [Interactive information tools for women facing a mastectomy].
AB  - Around 20 to 30% of women treated for breast cancer undergo a mastectomy in
      France. Of these patients, 70% do not have reconstructive surgery. It would seem
      that information surrounding reconstructive procedures is insufficient. Tools
      created in partnership with caregivers and patients are necessary to help women
      understand the choices they have.

PMID- 23878885
TI  - [Lymphedema after breast cancer surgery and research in physiotherapy].
AB  - The incidence of lymphoedema after breast cancer surgery with axillary dissection
      varies according to different studies, from 15 to 47%. The risk is 60% higher in
      cases of axillary radiotherapy. A rehabilitation service was undertaken as part
      of a research project aiming to show the benefit of the early treatment of
      lymphoedema of the arm.

PMID- 23878886
TI  - [A patient education program after breast cancer surgery].
AB  - In France, one woman in eight is treated for breast cancer before the age of 75.
      The 2009-2013 cancer plan recommends providing support for women after cancer. A
      therapeutic education programme helps them reintegrate into their daily life.

PMID- 23878887
TI  - [The nurse hypnotherapist in oncology].
AB  - Hypnosis is a non-medication based approach used increasingly in hospitals. In
      oncology, practised by a trained nurse hypnotherapist, it represents a
      complementary medicine.

PMID- 23878888
TI  - [Breast cancer and body image].
AB  - The treatment of breast cancer generates changes to the body and a person's self
      image. The caregivers' support focuses on the woman's grief for her old body and
      the acceptance of a changed intimacy. Listening to each woman is essential for
      acknowledging her fears in the face of this mutated body, her desires and her
      questions, in order to favour the psychological healing.

PMID- 23878889
TI  - [Night work, a probable risk factor for breast cancer].

PMID- 23878890
TI  - [Bibliography. Breast cancer].

PMID- 23878891
TI  - [Q-methodology, an innovative technique for nursing research].
AB  - Q-Methodology offers an alternative to traditional methodological approaches. It
      is similar to qualitative methods while at the same time guaranteeing a
      statistical data analysis. It can be particularly interesting for the development
      of nursing sciences.

PMID- 23878892
TI  - [Critical pathways. Management planning approach to quality improvement].

PMID- 23878893
TI  - [History, present situation and perspectives of forensic age diagnostics of
      living persons].
AB  - Although age estimations of living persons have been carried out for a long time
      already, the importance of forensic age diagnostics has increased considerably
      since the beginning of the 1980s. The Study Group on Forensic Age Diagnostics of
      the German Society of Legal Medicine founded under the chairmanship of Prof. Dr.
      Gunther Geserick in March 2000 has published recommendations for age assessments
      in criminal proceedings, in pension matters as well as in civil and asylum
      proceedings. Based on regular meetings and proficiency tests, this study group
      makes an important contribution to quality assurance in age assessment. The
      introduction of radiation-free imaging procedures in age estimation practice is
      to be expected in the near future.

PMID- 23878894
TI  - [Sonographic examination on the time frame of ossification of the distal fibula
      epiphysis].
AB  - In order to increase the reliability of forensic age estimations in living
      adolescents and young adults without justification for X-ray examinations, the
      establishment of radiation-free imaging procedures is desirable. In this study,
      the ossification stage of the right-hand distal fibula epiphysis was
      sonographically determined prospectively in 309 male and 307 female healthy
      volunteers. For this purpose a four-stage classification system was used. A
      sonographically determined ossification stage 3 permits the proof of completion
      of age 13 in boys and the proof of completion of age 12 in girls. In case of an
      ossification stage 4 the completion of age 14 in boys and the completion of age
      13 in girls can be certified. In order to increase the level of reliability of
      age estimates, findings should be collected by at least two independent examiners
      who are experienced in the sonography of skeletons, followed by consensus
      building.

PMID- 23878895
TI  - [About the Geserick sign--a literature study].
AB  - Fractures of the medial and basal orbital wall as well as the petrous part of the
      temporal bone were described first in 1980 by a Berlin-based study group led by
      Geserick as new cranium findings resulting from a contrecoup mechanism.
      Experimental and comparative examinations revealed that indirect fractures of the
      orbital walls are caused by a coup action of the eyeballs, whereas the
      mechanogenesis of the petrous bone fractures continues to be unclear. The
      frequently combined occurrence with the orbital sign nonetheless permits an
      allocation to the contrecoup mechanism. Both signs are important criteria for
      forensic and clinical assessment of craniocerebral injuries.

PMID- 23878896
TI  - [Postmortem detection of accidental methadone intoxication in a 10-year-old
      girl].
AB  - Intoxications in children still account for a large part of the cases reported to
      poison control centres. Among drug intoxications, substitution drugs have gained
      in importance lately. Careless storage of take-home medications puts children
      living in the same household at risk. The authors report on a fatal case of a 10
      year-old girl who died from intoxication with methadone belonging to a carer. The
      accidental intoxication had not been diagnosed at the hospital where the girl was
      treated for suspected meningitis. The question of medical malpractice is
      discussed.

PMID- 23878897
TI  - [Medicolegal aspects of a survived suicide attempt by hanging].
AB  - Report on the clinical and medicolegal findings in a survived suicide attempt by
      hanging. A 39-year-old woman was found unconscious in a crouching position on the
      balcony of her flat. The hanging device was an electric cable running around her
      neck in a single loop and attached to the balcony wall. After removing the noose,
      resuscitation measures were started immediately. For 5 hours, the victim was at
      first in a comatose and then in a somnolent state. The period of amnesia covered
      also the preparations for the suicidal act. The forensic examination performed on
      the same day showed a reddish, streak-like hanging mark, pronounced signs of
      blood congestion with dense petechial haemorrhages in the facial skin, confluent
      haemorrhages in the conjunctivae as well as bleeding from the left external
      auditory canal. BAC was 2.2 per mil. On the basis of the findings and the
      clinical course, criminalistic and pathophysiological aspects of near-hanging are
      discussed.

PMID- 23878898
TI  - [Suicide under the influence of "magic mushrooms"].
AB  - Psilocybin/psilocin from so-called psychoactive mushrooms causes hallucinogenic
      effects. Especially for people with mental or psychiatric disorders ingestion of
      magic mushrooms may result in horror trips combined with the intention of self
      destruction and suicidal thoughts. Automutilation after consumption of
      hallucinogenic mushrooms has already been described. Our case report demonstrates
      the suicide of a man by self-inflicted cut and stab injuries. A causal connection
      between suicidal behaviour and previous ingestion of psychoactive mushrooms is
      discussed.

PMID- 23878899
TI  - High hurdles for HHS: needs new ways to lure first-time insured.

PMID- 23878900
TI  - Still a work in progress: providers skeptical of accuracy of CMS' physician
      compare website.

PMID- 23878901
TI  - Already feeling the heat: Docs rethinking payments as Sunshine Act looms.

PMID- 23878902
TI  - A change in status: same-sex couples eligible for benefits, tax breaks.

PMID- 23878903
TI  - Climate health: advocates of Obama plan predict fewer illnesses.

PMID- 23878904
TI  - Low risk, high cost: advanced prostate treatment not always beneficial.

PMID- 23878905
TI  - ECHO institute to expand doc 'telementoring'.

PMID- 23878906
TI  - Is doc-specific data next?: Ruling could pave way for release of physicians'
      Medicare claims information.

PMID- 23878907
TI  - Striking a balance: OIG's chief counsel talks kickbacks, EHR upcoding and ACO
      waivers. Interviewed by Joe Carlson.

PMID- 23878908
TI  - End the medical arms race: systems should put focus on best outcomes, not high
      tech equipment.

PMID- 23878909
TI  - Wellness now, value later: workplace programs have benefits, though not in the
      short run.

PMID- 23878910
TI  - States of awareness: grass-roots efforts aim to educate public on Affordable Care
      Act, clarify enrollment process for insurance exchanges.

PMID- 23878911
TI  - Going private: employers see benefits in choice of insurance exchanges.

PMID- 23878912
TI  - Time to comparison-SHOP.

PMID- 23878913
TI  - Largest not-for-profit hospital systems: ranked by total net revenue.

PMID- 23878914
TI  - Test limits meet resistance: CMS seeks to restrict new PET scans for Alzheimer's.

PMID- 23878916
TI  - Pioneers no more? A number of ACOs are still weighing whether to switch to
      another model.

PMID- 23878915
TI  - Perils ahead: employers cheer mandate's delay, but move leaves ACA open to new
      attacks.
AB  - When the Obama administration announced it was delaying enforcement of the
      employer mandate in the ACA for one year, employer groups celebrated. But others
      had some troubling questions. "One has to hope, however, that the administration
      has thought through the ramifications of this delay for the other provisions,"
      says Tim Jost, left, a law professor at Washington & Lee University.

PMID- 23878917
TI  - Targeting adverse events: effort aims to ensure health IT causing no harm.

PMID- 23878918
TI  - Under scrutiny: cardiologists feeling pressure over 70% criterion.

PMID- 23878919
TI  - Unresolved cases: more hospitals expected in kyphoplasty case.

PMID- 23878920
TI  - Always on the move: aging boomers, primary-care doc shortage keep traveling
      nurses in demand.

PMID- 23878921
TI  - Ethics of mental enhancement: do adults taking ADHD medication have an unfair
      advantage?

PMID- 23878922
TI  - The importance of basics: seventeen essential questions for outpatient oncology
      clinics.

PMID- 23878923
TI  - Across the board: Affordable Care Act prompting hospital trustees to pay closer
      attention to policies on patient billing, collection and bad debt.

PMID- 23878924
TI  - Repositioning reprocessing: hospitals see big potential for savings, but safety
      remains an issue for some.

PMID- 23878925
TI  - Hospital ceo turnover by state: ranked by chief executive turnover percentage in
      2012.

PMID- 23878926
TI  - Mono-ADP-ribosyltransferase as a potential pharmacological drug target in the GLP
      1 based therapy of obesity and diabetes mellitus type 2.
AB  - Glucagon-like peptide-1 (GLP-1) based therapy is well established for treating
      diabetes mellitus type 2. Moreover, GLP-1 receptor agonists influence weight
      loss, and have potential for treating obesity. GLP-1 receptor agonists should be
      administered in low doses, together with drugs that potentiate insulin release,
      to avoid some minor side effects. We have focused on incretin hormones,
      especially GLP-1 and its analogues. Here we discuss the effect of the third
      intracellular loop-derived peptide of GLP-1 receptor on intracellular mono-ADP
      ribosyltransferase and its role in regulating the receptor. We suggest that this
      intracellular mono-ADP-ribosyltransferase could constitute a possible novel
      pharmacological target in the treatment of diabetes mellitus type 2 and obesity.

PMID- 23878927
TI  - Microbial community analyses in biogas reactors by molecular methods.
AB  - Successful biogas production is based on stable or adaptable microbial community
      structure and activity which depends on type of substrate used and several
      physico-chemical conditions in the bioreactor. Monitoring those and the dynamics
      of microbiota is important for planning and optimizing the biogas process,
      avoiding critical points and reaching the maximum methane yield. Methanogens are
      extremely difficult to study with culture-based methods. Molecular methods for
      microbial community structure analysis in biogas reactors, which offer
      qualitative and quantitative information on bacterial and archaeal species and
      their microbial community changes, and causes for process instability are
      surveyed in this review. For comparative studies semi-quantitative, rapid and
      cheap techniques like T-RFLP, DGGE and TGGE are used. More laborious and
      expensive techniques with high-throughput like semi-quantitative FISH and DNA
      microarrays and also quantitative techniques like qPCR and sequencing are used
      for phylogenetic analysis. Technique type adequacy for certain study depends on
      what information is needed and on several advantages and disadvantages every
      technique possesses.

PMID- 23878928
TI  - Ion selective phosphotungestate and beta-cyclodextrin based membrane electrodes
      for stability-indicating determination of midodrine hydrochloride.
AB  - This paper reports the construction and evaluation of two ion selective
      electrodes for the determination midodrine hydrochloride (MD) by direct
      potentiometry in pure drug substance and in tablet formulations. Precipitation
      based technique was used for fabrication of the first membrane sensor (sensor 1)
      using phosphotungestate (PT) and dioctylphthalate (DOP) as cation exchanger and
      solvent mediator, respectively. beta-cyclodextrin (beta-CD)-based technique with
      PT as a fixed anionic site in PVC matrix was used for fabrication of the second
      membrane sensor (sensor 2). The proposed sensors showed fast, stable Nernstian
      responses of 54 and 56 mV/decade for sensors 1 and 2, respectively, across a
      relatively wide MD concentration range (1x 10(-4) to 1 x 10(-1) mol/L and 5 x 10(
      5) to 1 x 10(-1) mol/L for sensor 1 and 2, respectively) in the pH range of 5-7.
      Sensor I and sensor 2 can be used for three and two weeks, respectively without
      any measurable change in sensitivity. The suggested electrodes succeeded to
      determine intact MD in the presence of up to 10% of its degradation product and
      displayed good selectivity in presence of common inorganic and organic species.

PMID- 23878929
TI  - Cadmium (II) ions removal from aqueous solutions Using Romanian untreated fir
      tree sawdust a green biosorbent.
AB  - Biosorption of cadmium ions from synthetic aqueous solution using popular
      Romanian fir tree sawdust (Abies Alba) as biosorbent, was investigated in this
      work. Prior to its utilization the considered biomass was washed, dried and
      sieved without further chemical treatments. The biosorbent was characterized
      using humidity, density and elemental analysis determinations and FTIR. FTIR
      analysis indicated that, on the biomass surface hydroxyl and carboxyl groups are
      presented. The effect of different biosorption parameters was studied. Higher
      biomass quantity, neutral pH, slightly elevated temperature and high cadmium ions
      concentration are all favouring the biosorption process. Equilibrium (Langmuir
      and Freundlich isotherm), kinetics and thermodynamics of the considered
      biosorption process were discussed in details. Equilibrium was best described by
      the Langmuir isotherm, while the kinetic of the process was best described by the
      pseudo-second-order model, suggesting monolayer coverage and a chemisorption
      process. Thermodynamic parameters showed that cadmium biosorption process on fir
      tree sawdust is an endothermic process.

PMID- 23878930
TI  - Characterization of Slovenian wines using Multidimensional data analysis from
      simple enological descriptors.
AB  - Determination of the product's origin is one of the primary requirements when
      certifying a wine's authenticity. Significant research has described the
      possibilities of predicting a wine's origin using efficient methods of wine
      components' analyses connected with multivariate data analysis. The main goal of
      this study was to examine the discrimination ability of simple enological
      descriptors for the classification of Slovenian red and white wine samples
      according to their varieties and geographical origins. Another task was to
      investigate the inter-relations available among descriptors such as relative
      density, content of total acids, non-volatile acids and volatile acids, ash,
      reducing sugars, sugar-free extract, SO2, ethanol, pH, and an important
      additional variable - the sensorial quality of the wine, using correlation
      analysis, principal component analysis (PCA), and cluster analysis (CLU). 739 red
      and white wine samples were scanned on a Wine Scan FT 120, from wave numbers 926
      cm(-1) to 5012 cm(-1). The applied methods of linear discriminant analysis (LDA),
      general discriminant analysis (GDA), and artificial neural networks (ANN),
      demonstrated their power for authentication purposes.

PMID- 23878931
TI  - Application of carrier element free coprecipitation (CEFC) method for
      determination of Co(II), Cu(II) and Ni(II) ions in food and water samples.
AB  - A simple and highly sensitive separation and preconcentration procedure, which
      has minimal impact on the environment, has been developed. The procedure is based
      on the carrier element free coprecipitation (CEFC) of Co(II), Cu(II), and Ni(II)
      ions by using 2-{4-[2-(1H-indol-3-yl)ethyl]-3-(4-methylbenzyl)-5-oxo-4,5-dihydro-
      1H-1,2,4-triazol-l-yl}-N'-(pyridin-2-yl methylidene)acetohydrazide (IMOTPA), as
      an organic coprecipitant. The levels of analyte ions were determined by flame
      atomic absorption spectrometry (FAAS). The detection limits for Co(II), Cu(II)
      and Ni(II) ions were found to be 0.40, 0.16 and 0.17 microg L(-1), respectively,
      and the relative standard deviations for the analyte ions were lower than 3.0%.
      Spike tests and certified reference material analyses were performed to validate
      the method. The method was successfully applied for the determination of Co(II),
      Cu(II) and Ni(II) ions levels in sea and stream water as liquid samples and red
      pepper, black pepper, and peppermint as solid samples.

PMID- 23878932
TI  - Biochemical characterization of MurF from Streptococcus pneumoniae and the
      identification of a new MurF inhibitor through ligand-based virtual screening.
AB  - MurF is an essential bacterial enzyme that is involved in the last intracellular
      stage of peptidoglycan biosynthesis, and therefore it has the potential to be
      exploited as a target for the development of new antibacterials. Here, we report
      on the expression, purification and biochemical characterization of MurF from an
      important pathogen, Streptococcus pneumoniae. Additionally, ligand-based virtual
      screening was successfully used and a new hit compound with micromolar inhibitory
      activities against MurF enzymes from S. pneumoniae and Escherichia coli was
      identified.

PMID- 23878933
TI  - Synthesis, characterization, crystal structure, and biological studies of two new
      Cd (II) complexes with 4'-(4-chlorophenyl)-2,2' :6',2"-terpyridine (Clphtpy).
AB  - Two new Cd(II) complexes, with the ligand 4'-(4-chlorophenyl)-2,2':6',2"
      terpyridine (Clphtpy) formulated as: [Cd(Clphtpy)(NO3)2H2O] (1), and
      [Cd(Clphtpy)(N3)2]2 (2), have been synthesized and characterized by CHN elemental
      analysis as well as FT-IR, 1H NMR, absorption and emission spectroscopy, thermal
      analysis and analyzed structurally by X-ray single-crystal diffraction. The
      single crystal X-ray analysis showed that the coordination number in complex 1
      and 2 were seven and six with N3O4 and N6 coordination sphere, respectively. The
      antibacterial activities of the synthesized complexes were tested against four
      gram-positive and four gram-negative bacteria. A biological study of the
      complexes indicated that the complex 1 exhibited very good activity against most
      of the tested bacteria and its activity was better than gentamicin as a standard
      antibiotic.

PMID- 23878934
TI  - The design, synthesis, and antioxidant activity of amphiphilic oximes and
      amidoximes.
AB  - New amphiphilic benzamidoxime, benzoxime, and aliphatic oxime derivatives of
      glycolipid mimetics were synthesized. The total antioxidant capacity of these
      amphiphilic derivatives was evaluated using DPPH assay. The observed antioxidant
      activity was the highest for benzamidoxime derivatives and glycolipid mimetics
      with two oxime functionalities, followed by benzoxime derivatives, glycolipid
      mimetics with one oxime group, and dimers of oxime. Due to their amphiphilic
      structure, which was a guidance for compound design and synthesis, these novel
      amphiphilic compounds can be proposed as potential antioxidants for tackling
      oxidative processes in two-phase systems, either biological (cell membranes) or
      artificial (emulsions).

PMID- 23878935
TI  - Anthracene derivative covalently immobilized on sensing membrane as a fluorescent
      carrier for water assay.
AB  - This article describes an optical chemical sensor based on a fluorescent dye 1
      allyloxy-4-hydroxyanthracene-9, 10-dione (AHD) with terminal double bond, which
      is covalently bonded to quartz glass plate surface treated with a silanizing
      agent to prevent its leakage. The purpose of this work was to characterize and
      optimize the sensor for determining the water content in the acetone organic
      solvent. The sensor is resistant to swelling; the membrane possesses relatively
      long lifetime, short response and recovering time. The reversibility and
      reproducibility of the sensor are adequate for practical measurements.

PMID- 23878936
TI  - Cd(II) and Zn(II) coordination polymers assembled from benzoyltrifluoroacetone
      and 1,2-bis(4-pyridyl)ethane ancillary ligands.
AB  - Two novel cadmium(II) and zinc(II) metal-organic coordination polymers with a
      beta-diketone and N-donor ancillary ligands, [Cd(bpe)(btfa)2]n (1) and
      [Zn(bpe)(btfa)2]n (2), (Hbtfa = benzoyltrifluoroacetone and bpe = 1,2-bis(4
      pyridyl)ethane), have been prepared and characterized by elemental analysis, IR
      and 'H NMR spectroscopy, and studied by thermal gravimetric analysis as well as
      single crystal X-ray diffraction. The crystal and molecular structures of 1 and 2
      have been solved by X-ray diffraction and they turned out to be one-dimensional
      polymers with zigzag (1) and linear (2) dispositions of the metal atoms. These
      one-dimensional polymers are further connected to form a 3D supramolecular
      network by C-H--O and C-H--F interactions. Thermal stabilities of these polymeric
      complexes have also been investigated.

PMID- 23878937
TI  - First-order derivative UV spectrophotometric method for simultaneous measurement
      of delapril and manidipine in tablets.
AB  - A first-order derivative spectrophotometric (1D-UV) method was developed and
      validated for simultaneous determination of delapril (DEL) and manidipine (MAN)
      in tablets. The 1D-UV spectra were obtained using change lambda = 4.0 nm and
      wavelength set at 228 nm for DEL and 246 nm for MAN. The method was validated in
      accordance with the ICH requirements, involving the specificity, linearity,
      precision, accuracy, robustness and limits of detection and quantitation. The
      method showed high specificity in the presence of two drugs and formulation
      excipients and was linear over the concentration range of 18-54 microg mL(-1) (r2
      = 0.9994) for DEL and 6-18 microg mL(-1) (r2 = 0.9981) for MAN with adequate
      results for the precision (< or = 1.47%) and accuracy (98.98% for DEL and 100.50%
      for MAN). Moreover, the method proved to be robust by a Plackett-Burman
      experimental design evaluation. The proposed 'D-UV method was successfully
      applied for simultaneous analysis of DEL and MAN in tablets and can be used as
      alternative green method to separation techniques. The results were compared with
      the validated liquid chromatography, capillary electrophoresis and liquid
      chromatography-tandem mass spectrometry methods, showing non-significant
      difference.

PMID- 23878938
TI  - Preparation, characterization and gas permeation investigation of resorcinol
      formaldehyde polymer or carbon xerogels/tubular ceramic composites.
AB  - New very stable composites prepared by deposition of resorcinol-formaldehyde
      polymer (RF-) or carbon (C-) xerogels into walls of commercial porous tubular
      ceramics (TiO2-ZrO2 and alphaAl2O3-gammaAl203) were obtained by a sol-gel process
      followed by a drying and a pyrolytic (only for C-xerogel/ceramic composites)
      step. They were characterized by nitrogen adsorption-desorption, SEM and XRD, and
      tested for gas (H2, CH4, CO2 and CO) separation applications. Additional morpho
      structural information about the open-interconnected ultramicropore structure of
      composites was found by gas permeation investigation. Interesting results for H2
      permeance was obtained especially for RF-polymer/ceramic composites respecting
      Knudsen diffusion mechanism of gas permeance: H2 > CH4 > CO > CO2. The
      coexistence of Knudsen and surface diffusion mechanisms were confirmed.

PMID- 23878939
TI  - Study of the provenance and technology of Asian kris daggers by application of X
      ray analytical techniques and hardness testing.
AB  - Museum objects, such as the daggers presented in this study, contain a wealth of
      information regarding their role in certain historic periods, their potential
      users, the art of manufacture, the type of material used etc. Utilization of
      various modern instrumental techniques facilitates compositional information
      about the unknown artifact under investigation. In this study, a set of
      traditional Asian daggers called kris or keris, with scarce information about
      their entry into museum collections, their origin, the type of material used, the
      date of production, etc., were analysed by Energy Dispersive X-ray Fluorescence
      spectrometry (EDXRF), Proton Induced X-ray Emission (PIXE) and hardness
      measurements. In this way, the traditional procedure of historian inspection was
      supplemented by the scientific approach to obtain information about the
      artifacts.

PMID- 23878940
TI  - Nano magnetic solid phase extraction for preconcentration of lead ions in
      environmental samples by a newly synthesized reagent.
AB  - In this study, magnetite nanoparticles with particle size lower than 47 nm were
      synthesized and were applied for preconcentration of Pb2+ ions from aqueous
      solutions. To preconcentrate the Pb2+ ions, the surface of the synthesized nano
      particles was modified with sodium dodecyl sulfate (SDS) as an anionic
      surfactant. A new chelating agent (2-((E)-2-amino-4,5
      dinitrophenylimino)methyl)phenol) was synthesized and used to form a very stable
      complex with Pb2+ ions. The lead ions formed complexes and were quantitatively
      extracted with SDS-coated magnetite nanoparticles. After magnetic separation of
      adsorbent, the adsorbent was eluted with 0.5% (v/v) HC1 in dimethyl sulfoxide
      (DMSO) prior to analysis by flame atomic absorption spectrometry (FAAS).
      Orthogonal array design (OAD) was used to study and optimize the different
      experimental parameters. Under the optimum conditions, enhancement factor up to
      63.5 was achieved for extraction from only 10 mL of sample solution and the
      relative standard deviation (RSD %) of the method was lower than 2.8%. The
      obtained calibration curve was linear in the range of 1-300 pg L-' with
      reasonable linearity (r2 > 0.998). The limit of detection (LOD) based on S/N = 3
      was 0.04 microg L(-1) for 10 mL sample volumes. Finally, applicability of the
      proposed method was successfully confirmed by preconcentration and determination
      of trace amounts of lead ions in environmental samples and satisfactory results
      were obtained.

PMID- 23878941
TI  - Design and evaluation of biological activity of diazenecarboxamide-extended
      cisplatin and carboplatin analogues.
AB  - Construction of a library of structurally diverse diazenecarboxamide-extended cis
      [Pt(2-picolyl-1,2,3-triazole)Cl2,] and cis-[Pt(propan-1,3-diamine)CBDCA] (CBDCA =
      1,1 -cyclobutanedicarboxylate) complexes 1-4 is described. These compounds retain
      oxidative properties of parent diazenecarboxamides against glutathione as
      demonstrated by NMR spectroscopy and high resolution mass spectrometry
      experiments. Cytotoxic activity of 1-4 was investigated against human cervical
      carcinoma HeLa cells. Four library members were found to possess moderate
      cytotoxic activity. Some model compounds were also examined, returning [PtCl2L2]
      (L = 1-(2-picolyl)-4-phenyl-1H-1,2,3-triazole) as the most potent under this
      investigation with IC50 of 19.05 microM, comparable to that of cisplatin (IC50 =
      16.3 microM).

PMID- 23878942
TI  - Multivariate analysis and chemometric characterisation of textile wastewater
      streams.
AB  - The aim of this work was to design a quick and reliable method for the evaluation
      and classification of wastewater streams into treatable and non-treatable
      effluents for reuse/recycling. Different chemometric methods were used for this
      purpose handling the enormous amount of data, and additionally to find any hidden
      information, which would increase our knowledge and improve the classification.
      The data obtained from the processes description, together with the analytical
      results of measured parameters' characterising the wastewater of a particular
      process, enabled us to build a fast-decision model for separating different
      textile wastewater outlets. Altogether 49 wastewater samples from the textile
      finishing company were analysed, and 19 different physical chemical measurements
      were performed for each of them. The resulting classification model was aimed at
      an automated decision about the choice of treatment technologies or a prediction
      about the reusability of wastewaters within any textile finishing or other
      company having similar characteristics of wastewater streams.

PMID- 23878943
TI  - Conventional and ultrasound-assisted extraction of anthocyanins from blackberry
      and sweet cherry cultivars.
AB  - Blackberry and sweet cherry are important plant foods rich in anthocyanins well
      known for their pharmacological and antioxidant effects. The aim of the present
      paper was to comparatively investigate conventional and ultrasound-assisted
      extraction procedures in order to isolate an enriched crude anthocyanin extract
      from blackberry (Thornfree cultivar) and sweet cherry (Black Gold cultivar).
      Hydroethanolic solution and acidified ethanol were used to conventionally extract
      anthocyanins by a discontinuous process at 4 degreeC for 2/ 24 hours. Added
      hydrochloric acid in ethanol of different concentrations proved to be more
      efficient in both type of samples. In the ultrasound-assisted extraction, the
      highest recovered anthocyanin content in blackberry (107.81 mg 100 g(-1) FM) was
      obtained with a 10/1 solvent/solid ratio (v/w) at 30 degreeC for 5 minutes, while
      a 15/1 solvent/solid ratio (v/w) at 30 degreeC for 20 minutes lead to an
      increased antioxidant capacity as determined by ferric reducing antioxidant power
      in the extract using 0.1% HCI in 80% ethanol. The optimum conditions obtained for
      ultrasound-assisted extraction from sweet cherry in 0.1% HCI in 60% ethanol at 30
      degree C include a 15/1 solid/solvent ratio (w/v) and 5 minutes for the maximum
      yield (36.05 mg 100(-1) FM). The final crude anthocyanin extracts may find useful
      application as dietary supplements, or may be further purified for application as
      food ingredients.

PMID- 23878944
TI  - Ion-association complexes of gallium(III)-4-(2-pyridylazo)-resorcinol anionic
      chelates and dicationic tetrazolium reagents.
AB  - The formation and liquid-liquid extraction of ion-association complexes between
      gallium(III)-4-(2-pyridylazo)resorcinol (PAR) anionic chelates and cations of
      four ditetrazolium chlorides (DT2+) were studied: Neotetrazolium chloride (NTC),
      Blue Tetrazolium chloride (BTC), Nitro Blue Tetrazolium chloride (NBT) and
      Tetranitro Blue Tetrazolium chloride (TNBT). The optimum extraction
      spectrophotometric conditions, composition of the extracted species {1:2:1 and/or
      1:2:2 (Ga:PAR:DT)}, some equilibrium constants {constants of association (beta),
      constants of distribution (KD and constants of extraction (Kex)} and analytical
      characteristics {molar absorptivity (epsilon), Sandell's sensitivity, intervals
      of adherence to Beer's law, etc.} were found. Relationships involving the number
      of nitro groups in DT2+ (Nnitro; DT2+ = BT2+, NBT2+ and TNBT2+) or molecular mass
      of DT2+ (MM; DT2+ = NT2+ and BT2+) were discussed: Log beta =f(Nnitro), Log KD
      =f(Nnitro), Log Kepsilon=f(Nnitro), Log epsilon =f(Nnitro) and Log beta = f(Log
      MM).

PMID- 23878945
TI  - Synthesis, characterization and X-ray structure of the adducts of bis(O
      butyldithiocarbonato)nickel(II) with substituted pyridines.
AB  - Some mixed ligand complexes of Ni(II) with O-butyldithiocarbonate as a primary
      ligand and substituted pyridines as secondary ligands have been isolated and
      characterized on the basis of analytical data, molar conductance, magnetic
      susceptibility, electronic and infrared spectral studies. The molar conductance
      studies show their non-electrolytic behavior. Magnetic and electronic spectral
      studies suggest octahedral stereochemistry around Ni(II) ions. Infrared spectral
      studies suggest bidentate chelating behavior of O-butyldithiocarbonate monoanion
      while other ligands show unidentate behavior in their complexes. One of the
      adduct bis(O-butyldithiocarbonato)bis(3,5-dimethylpyridine)nickel(II)
      crystallizes in the monoclinic space group P21/c with unit cell parameters. The
      crystal structure has been solved by direct methods and refined by full matrix
      least-squares procedures to a final R-value of 0.0379 for 2460 observed
      reflections. The Ni2+ ion is in a octahedral coordination environment formed by
      an N2S4 donor set, defined by two chelating dithiocarbonate anions as well as two
      3,5-dimethylpyridine ligands with the Ni2+ ion located at the inversion centre.
      The packing of layers of molecules is stabilized by weak pi-pi and C-H---pi
      interactions.

PMID- 23878946
TI  - A novel method for the one-pot five-component synthesis of highly functionalized
      pyranopyrazoles catalyzed by CuI nanoparticles.
AB  - A novel one-pot, five-component reaction for the synthesis of highly
      functionalized pyranopyrazoles from acid chlorides, Meldrum's acid, hydrazine
      hydrate, aromatic aldehydes and malononitrile in the presence of catalytic amount
      of CuI nanoparticles in aqueous media is reported. This method provides several
      benefits such as in situ preparation of beta-ketoester, mild reaction conditions,
      and environmentally friendly, waste-free and simple work-up procedure with
      excellent yields. The catalyst could be recovered and reused for several times
      with almost consistent catalytic activity.

PMID- 23878947
TI  - Robust optimization of psychotropic drug mixture separation in hydrophilic
      interaction liquid chromatography.
AB  - This paper presents multiobjective optimization of complex mixtures separation in
      hydrophilic interaction liquid chromatography (HILIC). The selected model mixture
      consisted of five psychotropic drugs: clozapine, thioridazine, sulpiride,
      pheniramine and lamotrigine. Three factors related to the mobile phase
      composition (acetonitrile content, pH of the water phase and concentration of
      ammonium acetate) were optimized in order to achieve the following goals: maximal
      separation quality, minimal total analysis duration and robustness of an optimum.
      The consideration of robustness in early phases of the method development
      provides reliable methods with low risk for failure in validation phase. The
      simultaneous optimization of all goals was achieved by multiple threshold
      approach combined with grid point search. The identified optimal separation
      conditions (acetonitrile content 83%, pH of the water phase 3.5 and ammonium
      acetate content in water phase 14 mM) were experimentally verified.

PMID- 23878948
TI  - Theoretical study on the protonation of cucurbit[7]uril.
AB  - By using quantum mechanical DFT calculations, the most probable structures of the
      cucurbit[7]urilH3O+ and cucur-bit[7]uril'(H3O+)2 cationic complex species were
      derived. In these two complexes having a plane symmetry, each of the considered
      H3O+ cations is bound by relatively strong hydrogen bonds to the corresponding
      carbonyl oxygens of the parent cucurbit[7]uril macrocycle.

PMID- 23878949
TI  - Quantitative structure-retention relationship analysis of some xylofuranose
      derivatives by linear multivariate method.
AB  - The relationship between retention behavior of eight 1,2-O-cyclohexylidene
      xylofuranose derivatives and their molecular characteristics was studied using
      chemometric Quantitative Structure-Retention Relationships (QSRR) approach. QSRR
      analysis was carried out on the retention parameter RM0, obtained by normal-phase
      thin-layer chromatography, by using molecular descriptors, as well as partition
      coefficient for n-octanol/water bi-phase system (logP). Molecular descriptors
      were calculated from the optimized structures. Principal component analysis (PCA)
      followed by hierarchical cluster analysis (HCA) and multiple linear regression
      (MLR) was performed in order to select molecular descriptors that best describe
      the retention behavior of the compounds investigated, and to determine the
      similarities between molecules. MLR equations, that represent the retention
      measure RMo as a function of the in silico molecular descriptors were
      established. The statistical quality of the generated mathematical models was
      determined by standard statistical measures and cross-validation parameters.
      Obtained results indicate that previously mentioned mathematical models are
      statistically significant and can successfully predict retention behavior of
      examined xylofuranose derivatives.

PMID- 23878950
TI  - Computing fourth atom-bond connectivity index of v-phenylenic nanotubes and
      nanotori.
AB  - Among topological descriptors connectivity topological indices are very important
      and they have a prominent role in chemistry. One of them is atom-bond
      connectivity (ABC) index defined as ABC(G)= [formula:see text], in which degree
      of vertex v denoted by dv . Recently, a new version of atom-bond connectivity
      (ABC4) index was introduced by M. Ghorbani et.al in 2010 and is defined as
      ABC4(G)= [formula: see text], where Su = [formula: see text] and NG(u)=[formula:
      see text]. In this paper we compute this new topological index for v-phenylenic
      nanotube and nanotori.

PMID- 23878951
TI  - Online system for knowledge assessment enhances students' results on school
      knowledge test.
AB  - Variety of online tools were built to help assessing students' performance in
      school. Many teachers changed their methods of assessment from paper-and-pencil
      (P&P) to online systems. In this study we analyse the influence that using an
      online system for knowledge assessment has on students' knowledge. Based on both
      a literature study and our own research we designed and built an online system
      for knowledge assessment. The system is evaluated using two groups of primary
      school teachers and students (N = 686) in Slovenia: an experimental and a control
      group. Students solved P&P exams on several occasions. The experimental group was
      allowed to access the system either at school or at home for a limited period
      during the presentation of a selected school topic. Students in the experimental
      group were able to solve tasks and compare their own achievements with those of
      their coevals. A comparison of the P&P school exams results achieved by both
      groups revealed a positive effect on subject topic comprehension for those with
      access to the online self-assessment system.

PMID- 23878952
TI  - Evaluation of the uncertainty budget for 226Ra analysis in water samples.
AB  - An alpha spectrometric method for the rapid determination of 226Ra isotope in
      water samples is presented. The method is based on the co-precipitation of
      (Ba)(Ra)SO4 for source preparation. The parameters contributing to the
      uncertainty budget are investigated. Geometry factor (solid angle / 4pi) was used
      instead of 226Ra standard disc for the determination of detector efficiency. The
      analytical method has been successfully applied to the determination of 226Ra for
      water samples in proficiency tests organized by International Atomic Energy
      Agency (IAEA) and National Physical Laboratory (NPL). The proposed method also
      showed high reproducibility.

PMID- 23878953
TI  - Ring Opening Metathesis Polymerisation (ROMP) as a tool for polyHIPes with
      extraordinary mechanical properties.
AB  - PolyHIPE materials have been prepared by Ring Opening Metathesis Polymerisation
      (ROMP) of dicyclopentadiene. Two characteristic features for successful
      stabilization of high internal phase emulsions (HIPEs) were tuned in order to
      achieve improvements regarding mechanical properties of polyHIPEs. Mechanical
      properties of the new materials were related to variations of the surfactant
      concentration and the volume ratio of the internal phase in HIPEs. Values for
      Young's moduli were about a hundred times higher than in standard polyHIPE
      materials with the same level of porosity, which represents a major improvement
      for highly porous cellular polymeric materials. Moreover, fully interconnected
      macroporous morphology was found for polyHIPEs, where respective HIPEs were
      stabilized with only 0.25 v% of surfactant.

PMID- 23878954
TI  - [70 years of Nikola Tesla studies].
AB  - Nikola Tesla's studies of chemistry are described including his not very
      scholarly affair in Maribor. After almost a century and half of hypothesis at
      least usable scenario of Tesla's life and "work" in Maribor is provided. The
      chemistry achievements of Tesla's most influential professors Martin Sekulic and
      Tesla's Graz professors are put into the limelight. The fact that Tesla in Graz
      studied on the technological chemistry Faculty of Polytechnic is focused.

PMID- 23878955
TI  - [Reports from the Slovenia Chemical Society on matters in 2012].

PMID- 23878956
TI  - Development of high-throughput quantum dot biosensor against Polymyxa species.
AB  - The plasmodiophoromycete Polymyxa betae and P. graminis are eukaryotic biotrophic
      parasites residing in the roots of chenopodiacae and gramineae plants. They are
      natural transmitting agents of several important plant viruses such as are beet
      necrotic yellow vein virus (BNYW), beet soil borne mosaic virus (BSBMV), wheat
      soil-borne mosaic virus (WSBMV). Developing advanced high-throughput diagnostic
      methods capable of accurate detection of these pathogens could assist with the
      screening programs and consequently with the development of disease-resistant
      germplasms. In the present study, a previously developed quantum dots (QDs) FRET
      based nano-biosensor was upgraded to a high-throughput version. QDs were
      functionalized with a specific antibody against the P. betae's specific
      glutathione-S-transferase (GST) protein. On the other hand, GST was conjugated to
      Rhodamine dye. Ninety six-well polystyrene plates were used as the detection
      platform. The mutual affinity of the antigen and the antibody brought the CdTe
      QDs and rhodamine together close enough to allow the resonance dipole-dipole
      coupling required for fluorescence resonance energy transfer (FRET) to occur. The
      immunosensor constructed showed a high sensitivity and specificity of 100%, and
      was successfully used for high-throughput screening of 96 real samples with
      consistent results within the course of less than 30 minutes.

PMID- 23878957
TI  - Use of Arabidopsis thaliana to study mechanisms of control of Verticillium wilt
      by Pseudomonas fluorescens PICF7.
AB  - Verticillium wilt (VW), caused by Verticillium dahliae Kleb., is an important
      disease in many crops and its effective management has proven difficult. Among
      the various disease control measures to be implemented, the use of microbial
      antagonists (biological control agents, BCAs) constitutes an environmentally
      friendly approach fitting criteria of modern sustainable agriculture. Pseudomonas
      fluorescens PICF7 was isolated from root tissues of nursery--propagated olive
      plants. Selection of this strain was based on in vitro growth inhibition of V.
      dahliae, colonizing ability of olive roots, endophytic lifestyle, and control of
      the highly-virulent defoliating (D) pathotype of V. dahliae in olive planting
      stocks. The mode of action by which PICF7 controls VW in olive is as yet unknown;
      moreover, to uncover potential biocontrol mechanisms poses additional
      difficulties in this pathosystem because the target is a tree. Therefore we used
      the model plant Arabidopsis thaliana to study: i) if PICF7 colonizes the
      rhizosphere of A. thaliana; ii) disease symptoms caused by V. dahliae in A.
      thaliana; iii) control of VW by PICF7 in different accessions and mutants of A.
      thaliana; and iv) if motility, antibiosis and/or siderophores are involved in
      control of V. dahliae by PICF7. Diverse bioassays were conducted and in all of
      them both the BCA and the pathogen were introduced in the rhizosphere of A.
      thaliana. Both D and non-defoliating isolates of V. dahliae caused disease
      symptoms in A. thaliana. PICF7 colonized and persisted in the rhizosphere of
      different Arabidopsis accessions and could control the D pathotype in some of
      them. PICF7 mutants affected in antibiosis significantly lost their ability to
      control VW in A. thaliana. We conclude that the model plant A. thaliana is useful
      to unravel interactions between this BCA and V. dahliae.

PMID- 23878958
TI  - Growth biostimulation of quorum-quenching bacteria by gammagamma-heptalactone
      treatment in the hydroponic rhizosphere of Solanum tuberosum.
AB  - Several bacterial plant pathogens, including Pectobacterium, use a cell-to-cell
      communication system called quorum sensing (QS) to synchronize and regulate
      expression of the virulence factors. In this study, the biomolecule gamma
      heptalactone (GHL) was introduced in hydroponic culture of Solanum tuberosum to
      stimulate growth of the native rhizospheric bacteria which are able to degrade
      the QS signal, hence potentially quench the QS-regulated virulence of
      Pectobacterium. During two annual campaigns, GHL-treatment efficiently stimulated
      the growth of QS-degrading bacterial population of Rhodococcus erythropolis in
      the rhizosphere of potato plants. Analytical chemistry showed that GHL rapidly
      disappeared because it could be assimilated as a carbon source by R.
      erythropolis. Moreover, pyrosequencing of the rrs-amplicons revealed a strong
      modification of the structure and diversity of bacterial populations, when GHL
      treated and untreated conditions were compared. This work highlighted a potential
      innovative strategy for stimulating the growth and root colonization of QS
      degrading bacteria, which would act as biocontrol agents against plant QS
      pathogens.

PMID- 23878960
TI  - Biocontrol of Fusarium wilt disease in cucumber with improvement of growth and
      mineral uptake using some antagonistic formulations.
AB  - Fusarium wilt disease in Cucumber (Cucumis sativus L.) is widespread, responsible
      for serious economic losses. Amongst totally 15 isolates of Fusarium spp.,
      obtained from different localities of Sohag governorate, Egypt, only the
      identified isolates as F. oxysporum were pathogenic on cucumber Denmark Beta
      Alpha cv. and caused wilt symptoms. Totally 22 isolates of Trichoderma spp., B.
      subtilis and Pseudomonas spp., were obtained from rhizosphere of cucumber and
      some available commercial formulations and then tested for antagonistic activity
      against F. oxysporum (FO5) in vitro. The highest inhibitory effect on growth of
      FO5 was observed by isolate Trichodex of T. harzianum (89.29%) followed by Th4 of
      T. harzianum, Serenade and MBI 600 of B. subtilis, PS3 of Pseudomonas spp., and
      Treico and Tv2 of T. viride. Pot experiments were performed to investigate the
      effects of formulated antagonists as seed treatment on Fusarium wilt incidence,
      growth and mineral uptake of cucumber. Results showed that all tested
      formulations significantly reduced percent of wilted plants and disease severity,
      and improved plant growth by increasing length of shoot and root, fresh and dry
      weight of shoot and root system, and number of leaves and flowers per plant
      compared with untreated control. They also significantly increased nutrient
      contents of plant shoot including N, P, K, Ca, Fe, Mn, Cu, and Zn. Magnesium
      content in shoot slightly not significantly increased. Formulation of Trichodex
      was the most effective ones followed by Serenade, Th4 and PS3.

PMID- 23878959
TI  - Induction of resistance in wheat against powdery mildew by bacterial cyclic
      lipopeptides.
AB  - In conventional agricultural practices, fungicides are extensively used to
      control the development of many fungal plant pathogens. However, the reduction of
      pesticide applications in the field, which is recommended by authorities and
      approved by public opinion, may lead to a re-emergence of diseases. Alternative
      strategies have therefore to be developed in order to control fungal infection;
      one of them is based on plants natural resistance reinforcement caused by
      elicitors. Our project aims at characterizing mycosubtilin, surfactin and
      fengycin, three bacterial cyclic non-ribosomal lipopeptides produced by the
      rhizobacterium Bacillus subtilis, for their ability to induce resistance in wheat
      against powdery mildew (Blumeria graminis f.sp. tritici). RT-qPCR approach was
      used to investigate effect of lipopeptides on expression pattern of defence
      related genes, such as PR protein-encoding genes or genes involved in plant
      defence pathways (reactive oxygen species (ROS) metabolism, lipid peroxidation,
      phenylpropanoid and octadecanoid pathways) in response to fungus and revealed
      that expression of LOX and PR1 was strongly induced by surfactin at 24h and 18h
      after inoculation, respectively. Mycosubtilin seemed to be more efficace to
      induce expression of OXO and Ltp. Surfactin could also induce expression of
      chitinase encoding genes but neither surfactin nor mycosubtilin could induce the
      expression of GSTphi and PAL genes in response to the fungus.

PMID- 23878961
TI  - Efficacy of Trichoderma asperellum oil formulations on the control of cocoa black
      pod disease (Phytophthora megakarya).
AB  - The objective of this study was therefore to develop a formulation of conidia of
      T. asperellum with the aim of improving its efficacy. The formulations developed
      were oily dispersions. It was a combination of solvents consisting of groundnut
      oil or palm oil with structural agents and emulsifying-dispersing agents.
      Emulsification tests were carried out and the stability of the emulsions
      evaluated. The evaluation of the effect of co-formulants on the growth of conidia
      of T. asperellum was done by reading the optical densities of the formulated
      samples on multi-plates using a plate reader. The test on detached cocoa pods was
      done by treating the cocoa pods with selected formulations at 1.10(7) conidia/ml
      and inoculation of the treated cocoa pods was done 24 hours later with zoospores
      of P. megakarya at 1.10(5) zoospores/ml. The growth of necrosis on the fruits was
      measured daily. The screening of co-formulants and emulsification tests ended up
      with the selection of two formulations. The first composed of conidia of T.
      asperellum, groundnut oil, Tensiofix NTM and Tensiofix 869. The second differed
      from the first by utilisation of palm oil as the solvent. These formulations
      proved stable when diluted in water with 1% and 0.5% of sedimentation
      respectively after 24 hours. The viability test of the conidia indicated that the
      different formulations selected did not have a fungitoxic effect. The test on
      detached cocoa pods showed an improved efficacy of T. asperellum to control the
      disease. The growth rates of necrosis were 6.29 mm/day, 7.25 mm/day and 31.6
      mm/day for treatment with formulation 1, pure conidia and control treated with
      water respectively.

PMID- 23878962
TI  - Effects of silicates from scaps of photovoltaic industries on powdery mildew of
      zucchini.
AB  - Silicon is the second most abundant element on earth's surface and its use can
      stimulate natural defense mechanisms in plants. The effect of silicate from
      scraps of photovoltaic industries against powdery mildew on zucchini (Cucurbita
      pepo) was evaluated under greenhouse conditions. Potted plants were inoculated
      with a spore suspension containing 1 x 10(5) cfu/ml. The following treatments
      have been carried out, 3 and 10 days after pathogen inoculation: chemical
      fungicide (propiconazole, TILT 25 EC, Syngenta); Bacillus subtilis (250 g/hl,
      Serenade, Intrachem); 1% and 0.1% sodium silicate (r = 1); 1% and 0.1% sodium
      silicate (r = 2); tap water as control. Disease incidence and severity were
      assessed 7, 14 and 21days after pathogen inoculation. Results showed that the
      application of 1% sodium silicate (r = 1) significantly reduced the powdery
      mildew to a level similar to chemical control. The other treatments, including
      Bacillus subtilis, reduced disease severity compared to water control, but were
      less efficient. The use of silicates from photovoltaic industries is a valid
      alternative for the control of powdery mildew on zucchini, in particular in
      organic farming. However, silicates might not be sufficient at higher disease
      incidence levels, and their use is more suitable within an integrated disease
      control strategy.

PMID- 23878963
TI  - Survival of Alternaria alternata during anaerobic digestion of biomass in stirred
      tank reactors.
AB  - The survival of Alternaria alternate during anaerobic digestion was investigated
      in context of a joint research project. The aim of this project was to estimate
      the phytosanitary risk of dissemination of pathogens by returning treated biomass
      as organic fertilizer to arable land. The studies were carried out in lab-scale
      stirred tank reactors under mesophilic conditions. After insertion of infected
      plant material into the reactors the influence on the viability of the fungal
      pathogen was studied concerning exposure time, pretreatment and storage of the
      digestates for four weeks or six months. The results clearly showed that
      anaerobic digestion leads to a complete inactivation of A. alternate already
      after an exposure time of six hours.

PMID- 23878964
TI  - Evolution of Mycosphaerella graminicola resistance to epoxiconazole and pyrifenox
      in northern France.
AB  - DMIs have been for many years the most used antifungal compounds against Septoria
      tritici blotch caused by Mycosphaerella graminicola, the most important foliar
      disease on winter wheat worldwide. Their use leads to a development and
      widespread of isolates with reduced sensitivity in several populations around
      Europe, especially in France. Here, we investigated the resistance level to
      epoxiconazole and pyrifenox of 48 M. graminicola isolates (24 from 2009 and 24
      from 2011) sampled in Nord-Pas de Calais (France) from two untreated plots
      naturally infected by the fungus. The resistance levels were determined by
      microplate assays at 10 different concentrations for each fungicide (geometric
      progression x 3.5). Overall, IC50 (half maximal inhibitory concentration) values
      were slightly higher in the 2011-isolates compared to the 2009-isolates. For the
      2009-isolates, IC50 values ranged from 0.14 mg/L to 2.25 mg/L and from 0.10 mg/L
      to 2.19 mg/L for epoxiconazole and pyrifenox, respectively, while IC50 values for
      2011-isolates ranged from 0.10 mg/L to 22.13 mg/L and from 0.07 mg/L to 11.63
      mg/L for epoxiconazole and pyrifenox, respectively. The determination of
      resistant factors (IC50 resistant isolate/IC50 sensitive isolate) revealed an
      increase of rates of isolates showing a resistant factor higher than 100 from 21%
      to 62 % for epoxiconazole and from 8% to 42% for pyrifenox between 2009 and 2011.
      Furthermore, statistical analyses revealed a positive correlation between
      resistances to epoxiconazole and pyrifenox in both years, indicating that most of
      isolates resistant for epoxiconazole are also resistant for pyrifenox. This study
      shows a shift in sensitivity to epoxiconazole and pyrifenox in northern France
      between 2009 and 2011 and suggests a relationship between resistance to
      epoxiconazole and pyrifenox in M. graminicola.

PMID- 23878965
TI  - Evaluation of plant resistance inducers on different winter soft wheat cultivars
      against Septoria leaf blotch.
AB  - Septoria tritici blotch (STB) caused by Mycosphaerella graminicola (anamorph:
      Zymoseptoria tritici) is one of the most devastating foliar diseases on bread
      wheat (Triticum aestivum L.). Because of the emergence of fungal strains highly
      resistant to mainly used fungicides and the deleterious impacts of these
      fungicides on the environment, development of alternative control strategies to
      protect wheat crops against STB is needed. The induction of plant resistance by
      elicitors is likely to be a helpful alternative. Our study aims at characterizing
      the efficiency of potential resistance inducers towards STB in three bread wheat
      cultivars differing in their resistance levels to the pathogen: Alixan
      (susceptible), Premio (moderately resistant) and Altigo (resistant). These
      cultivars were inoculated under controlled and semi-controlled conditions with
      the pathogenic M. graminicolo strain T01193 in order to assess the protective
      effect of three potential resistance inducers against the disease. Moreover, the
      direct antifungal effect bf these products was evaluated in vitro at different
      concentrations in order to verify their potential biocide activity. Furthermore,
      cytological analyses were performed in order to determine the effects of these
      products on the fungal infection process and to compare these effects among the
      three wheat cultivars. Finally, reactive oxygen species metabolism was
      investigated in the three cultivars during their interaction with T01193 by
      measuring peroxidase activity.

PMID- 23878966
TI  - Effect of a fungal infection on the profile of volatile organic compounds emitted
      by plant roots.
AB  - It is known since few years that the aerial and underground parts of the plants
      emit volatile organic compounds (VOCs) that can interact with other organisms of
      the environment. They are involved in the attraction of seed dispersers and
      pollinators, the repellence of enemies via direct or indirect mechanisms and the
      induction of defence systems in other parts of the same plant or in other plants
      in the vicinity (Dudareva et al., 2006). It has been shown previously that the
      VOCs spectrum emitted by plants hardly depends on their physiological state (Kant
      et al., 2009). However those phenomenons were poorly studied at the edaphic
      level. Thus, the Rhizovol project, a multidisciplinary project in Gembloux Agro
      Bio Tech was set up to study the emissions of VOCs by plant roots and their
      interactions with other organisms of the rhizosphere. As a partner of this
      project, the Plant Pathology Unit of Gembloux Agro-Bio Tech chose to study the
      effect of a fungal infection on the profile of VOCs emitted by plant roots, based
      on three model organisms, barley (Hordeum vulgare L.), since it is a major crop
      in Belgium that can suffer a large range of aggressions, and two pathogenic
      fungi, Cochliobolus sativus and Fusarium culmorum, responsible for root and foot
      rots and seedling blight on cereals (Wiese, 1977). Later in the development, C.
      sativus produces elongate brown-black lesions (spot blotch) and F. culmorum
      induces head blight and produces mycotoxins that make the grain unsuitable for
      consumption (Nielsen et al., 2011). The objective of this work was to identify
      the VOCs emitted during the dual interactions between barley roots and a
      pathogenic fungus. The study was performed in two steps; first, the independent
      analyses of the VOCs emitted by each of the partners (C. sativus, F. culmorum and
      healthy barley roots), then the analyses of the VOCs spectrum emitted during dual
      interactions.

PMID- 23878967
TI  - Aggressiveness study on Sclerotinia isolates from red clover crops.
AB  - Sclerotinia trifoliorum Erikks. causes clover rot (clover cancer, Sclerotinia
      crown and root rot) in red clover crops (Trifolium pratense L.), an important
      disease in Europe. Little is known about the aggressiveness of Scierotinia
      isolates and aggressiveness studies were never conducted on a European scale. In
      this study we compared the aggressiveness of 30 Sclerotinia isolates isolated
      from red clover crops in 25 locations in 12 European countries using a plant
      based bio-test. Plants from 6 red clover cultivars with different resistance
      levels were spray inoculated at the age of 12 weeks with 1 to 1.5 ml mycelium
      fragment suspension per plant. After 10 days incubation, plants were scored on a
      scale from 1 (healthy plant) to 5 (dead plant) and the disease index was
      calculated. The experiment was repeated 3 times and all repetitions were highly
      correlated. Average disease indices ranged from 52.6% to 82.7%. Significant
      differences were detected between isolates and between cultivars, but there was
      no isolate--cultivar interaction. Based on these results, the most aggressive
      isolates can be selected for resistance breeding. Future work should investigate
      whether the differences in aggressiveness are due to a higher growth speed or due
      to a higher secretion of cell-wall degrading components and pathogenicity
      factors.

PMID- 23878968
TI  - Isolation, cloning and large scale expression of glutathione-S-transferase (GST)
      protein of Polymyxa betae.
AB  - The plasmodiophoromycete Polymyxa betae, an obligate parasite of sugar-beet
      roots, is a natural vector of Beet necrotic yellow vein virus (BNYVV). To develop
      protein based diagnosis for any pathogenic agents including P. betae, a specific
      immunogenic protein has to be prepared. The glutathione-S-transferase (GST) is
      expressed in all the morphologically different stages of the pathogen's life
      cycle, and then it is a good candidate as an immunogenic agent for developing of
      specific antibodies and diagnostic purposes. The present study describes
      isolation, cloning and large scale expression and purification of P. betae GST
      protein. For this aim, total RNA was initially isolated from infected plants and
      corresponding cDNA was constructed by using reverse transcriptase and oligo-dT
      primer as well as mRNA as a template. The gene encoding GST was isolated and PCR
      amplified from the synthesized cDNA by using specific primers. The amplified
      fragments were preliminary cloned into pTZ57R/T cloning vector. Intact clone
      containing right sequence was selected after digestion, PCR amplification and
      subsequent sequencing analysis. Next, GST encoding region having right sequence
      was recovered and sub-cloned into pET28a bacterial expression vector. Large scale
      expression of recombinant protein was performed in BL21-de3 strain of E. coli and
      purification was carried out under native situation through Immobolized metal ion
      affinity chromatography (IMAC) in column containing Ni-NTA agarose beads.
      Successful expression and purification steps were confirmed by SDS-PAGE followed
      by western blotting analysis. These results confirmed the high purity and
      integrity of GST protein which was around 21 kDa. Generally, the total yield of
      the purified protein in the culture medium was estimated at around 3.5 mg/mL.
      After purification, a major part of the purified proteins was precipitated
      identified as excess GST. To improve the solubility, the final concentration of
      purified protein was reduced to 0.5 mg/mL.

PMID- 23878969
TI  - Effects of different fungicide treatments on grape, must and wine quality.
AB  - The aim of this study was to evaluate the effectiveness of natural products and
      low-rate copper formulations against grapevine downy mildew, in order to reduce
      or replace copper use in organic farming, and to assess the effects on the
      qualitative parameters of grape, must and wine of the different treatments. The
      trial was carried out in an organic vineyard in accordance with the EPPO/OEPP
      guidelines. Plots were prepared, each containing 12 vine-plants and repeated four
      times in randomized blocks. At harvest, representative grape samples were picked
      off from the plots treated with the different products: for each treatment, a
      random sub-sample was kept for analyses, the remaining part was processed to
      produce wine. Grapes, musts and wines were characterized for their food quality
      indices, as well as for their nutraceutical profiles and antioxidant activity. On
      must and wine, sugars, acidity and pH were determined according to official
      methods. On grape and wine, total polyphenol, flavonoid and hydroxycinnamic acid
      contents were determined by spectrophotometric analysis, as well as antioxidant
      activity tests. Organic acids and single polyphenols were also determined by
      HPLC. The results of the trial, characterized by moderate infection pressure,
      indicate that all tested products guaranteed a satisfactory control of Plasmopara
      viticola although the alternatives to copper were not as effective as copper.
      Data evidence that grape quality and its oenological potential were not
      significantly influenced by applied treatments and that they did not
      significantly differ in comparison with the untreated control, only with an
      interesting significant negative correlation between proanthocyanidins level and
      the severity of disease on ripe berries. The uniformity of data seems to evidence
      a general adaptation of plants to different treatment stresses, probably due both
      to low input of active ingredients and to moderate downy mildew infection.

PMID- 23878970
TI  - Natural resistance against pre- and post-harvest pathogens in Sardinian pears
      germoplasm.
AB  - Natural resistance against Venturia pirina and Botrytis cinerea was investigated
      within the Sardinian pears germplasm. The natural occurrence of V. pirina was
      monitored at the orchard level for 5 years, while resistance against B. cinerea
      was evaluated by a bioassay using methanolic extracts of the fruit rind or by
      artificially inoculation. Methanolic extracts of the leaves were employed for the
      Cladosporium bioassay on TLC plates. Among the accessions, 8 resulted sensitive
      to V. pirina, vegetation and fruit are severely affected every year. Seven showed
      an intermediate behaviour and the sole vegetation was affected slightly in two
      out of the 5 years. Two inhibition spots, in the methanolic extract of the
      leaves, were clearly evidenced in 55 accessions and a positive correlation was
      found between the presence of these antifungal compounds in the leaves and the
      resistance to V. pirina in the field. The artificial inoculation of fruit with B.
      cinerea evidenced a great variability in resistance, with about 12 accessions
      that could be considered having a good resistance. The fruit rind methanolic
      extracts evidenced several inhibition spots in most accessions, but no
      correlation could be found with fruit resistance to B. cinerea. In addition, the
      activity of the polygalacturonase inhibiting protein (PGIP), determined with an
      agarose diffusion bioassay, indicate a positive correlation between the PGIP
      activity evidenced in the core tissue and the infection degree by B. cinerea.

PMID- 23878971
TI  - Aggressiveness of Cephalosporium maydis causing late wilt of maize in Spain.
AB  - Late wilt of maize, caused by the vascular and soilborne pathogen Cephalosporium
      maydis, was identified in the Iberian Peninsula in 2008. During the last years
      the incidence and economical impact of the disease has importantly increased both
      in Portugal and Spain. Varieties of maize displaying tolerance to the pathogen
      are available, but the effectiveness can be dependent on the virulence of the
      fungus (i.e. ability to cause disease on a specific genotype). On the other hand,
      strains of crop pathogens from different geographic origins can differ with
      regard to the degree of disease caused on a specific genotype (i.e.
      aggressiveness). Our working hypothesis was that isolates of C. maydis from
      different maize growing areas may differ in aggressiveness towards maize plants.
      Seven fungal strains were isolated in 2009 from diseased plants collected in the
      most important maize growing regions of Spain and used to inoculate two
      susceptible maize varieties grown in shadehouse from March to July 2010. The
      experimental unit consisted of two 4-day-old seedlings planted in an 8-liter pot
      filled with sand/silt previously infested with 200 g of wheat grains colonized by
      the fungi. Non colonized wheat grains were used for the control treatments. Six
      replications (pots) were established for each variety/isolate combination
      according to a complete randomized 2 x 8 factorial design. The percentage of
      necrotic and dry aboveground tissues was recorded 14 weeks after inoculation and
      thereafter weekly until physiological senescence of the control plants. At the
      end of the experiment, weights of roots and aboveground parts of the plants were
      recorded. Initial occurrence of symptoms in the plants was significantly
      dependent on the isolate of C. maydis and on the maize variety. However, final
      severity of aboveground symptoms (leaf necroses and drying up) was only dependent
      on the fungal isolate. All the isolates significantly reduced the root weight of
      both varieties of maize. The highest root weight reductions were also associated
      to a significant low weight of above-ground parts. Considering all the symptoms
      analysed and their progression in the maize plants, our results reveal that a
      diversity of aggressiveness exists among isolates of C. maydis. The need for a
      characterization of maize genotypes by their reaction against highly aggressive
      isolates of the fungus in the Iberian Peninsula is suggested. This study is a
      first step towards a recommendation of crop varieties that are tolerant to C.
      maydis in different areas of the Iberian Peninsula. Future research aims at
      studying the relationship between aggressiveness levels, molecular
      characteristics and geographical origin whithin C. maydis.

PMID- 23878972
TI  - Import risk analysis of fruit from Spain to Italy.
AB  - The International trade has to ensure food security and preserve both human
      health and the diffusion of animal and plant diseases among different countries.
      While organic horticultural production and trade are regulated by global
      guidelines, no specific restrictions relay to conventional commodities and almost
      free import-export occurs among UE countries. Consequently, the safety
      characteristics of imported fresh crops have become an important issue. On the
      basis of these considerations, the aim of the present study is to monitor the
      epiphytic microflora (particularly yeasts and fungi) carried by fresh fruit,
      imported from Spain to Italy. Particular attention was given to pathogenic
      microrganisms and to natural antagonists. In addition, the resistance to a few
      postharvest fungicides was determined for the isolated strains and compared to
      the local ones. Apples, Citrus fruits, stone fruits, and persimmon fruit were
      sampled at arrival of the container from Spain at the wholesale market in Sassari
      (Italy), this to prevent fruit contamination by local strains of microrganisms.
      The isolation was performed by rinsing and shaking (30 min at 100 rpm) the fruit
      in a beaker with 500 mL of sterile water. After concentration (7.5 mL), 100
      microl of the rinse water was plated on potato dextrose agar (PDA). Isolation of
      pure colonies was performed by multiple streaking on plates, until unicellular
      cultures were obtained. Fifty three microrganisms, mainly fungi and yeasts, have
      been isolated and assayed in vitro and in vivo. Pathogenic behavior of isolated
      fungi was tested on fruits artificially wounded and only 7 strains out of 18
      isolates caused decay. The resistance to different concentrations of imazalil
      (IMZ), tiabendazolo and azoxystrobin were tested in vitro for the pathogenic
      isolates. All isolates were completely inhibited with 1000 ppm IMZ evidencing
      that no resistant strains were present on the imported fruit. Since the baseline
      resistance, found for all isolates, was similar to the indigenous strains, we may
      conclude from this risk analysis that the import of the studied fruits produced
      in the 4 geographical areas of Spain does not increase the local baseline
      resistance.

PMID- 23878973
TI  - Morphological and molecular characterisation of fungal populations possibly
      involved in the biological alteration of stones in historical buildings.
AB  - The deterioration process of historical building is progressive and irreversible,
      and the timing and mode of impact are different depending on the characteristics
      of building materials used, local microclimate, air pollution, presence of
      specific flora and fauna. The chemical and microbiological characterisation of
      building materials is mandatory in preventing and eventually recovering
      degradation effects. Ideally, the analysis of structural stones should be
      complete, efficient, rapid, and non destructive when dealing with a precious or
      unique construction. The investigation has been performed on a private historical
      building made using calcarenite stones and sited between the archaeological site
      of Lavello, a little town located in the Basilicata Region (South Italy), and the
      industrial area surrounding this town. To study in progress the degradation of
      stone materials, a new building sample (ca. 1 m3) was constructed by using the
      same stones (33 x 15cm), collected from a local quarry. The intact calcarenite
      stone was characterised by using different methods of surface analysis (XRD, XPS,
      SEM), and exposed to outdoor conditions. The analyses of the stone material were
      repeated after three and six months to early evaluate the progression of
      alterations and the forward modifications of calcarenite structure. After only
      three months of the new building sample exposure, the adopted analytical methods
      were able to provide a series of data, which allowed the assessment of the
      incipient modification of the stone surfaces. The degradation appeared worsened
      performing the same observations on sixth month replicates, suggesting that
      environmental conditions modified the structure and the compactness of stones and
      favoured the biological colonization of surfaces especially in the South-East
      direction of prevailing winds. For this reason the presence of fungi on the
      stones' surface was investigated and a morphological and molecular
      characterization of sampled fungi was performed. Several genera and species of
      fungi, possibly, involved in degradation were found. The most frequent colonies
      belonged to Alternaria (A. infectoria, A. citri and Alternaria sp.), Coprinopsis
      sp., Penicillium piceum, Fusatrium equiseti and Scytalidium termophilus.

PMID- 23878974
TI  - Pre-harvest treatments with fungicides and post-harvest dips in sodium
      bicarbonate to control postharvest decay in stone fruit.
AB  - The objective of this study was to evaluate the effectiveness of different
      commercial formulations of fungicides containing one or more active ingredients
      in controlling postharvest decay of Thyrinthos and Boccuccia apricots, Red top
      peaches and Caldesi nectarines. Field treatments consisted of two sprays with
      cupric compounds, at the end of leaf fall and before bud swelling, one with
      sulfur compound, at fruit about half final size stage, and one with one of the
      following commercial formulations at the label suggested rates, one week before
      harvest: Teldor (fenexamid 50%; Bayer Crop Protection), Folicur (Tebuconazole
      4.35%; Bayer Crop Protection), Signum (boscalid 26.7%, pyraclostrobin 6.7%; Basf
      Crop Protection), Score (difenoconazole 23.23%, Syngenta Crop Protection) and
      Switch (cyprodinil 37.5%, fludioxonil 25%, Syngenta Crop Protection). After
      harvest the fruit were stored for 1 week at 6 degrees C and 90% RH followed by 1
      week at 20 degrees C and 60% RH to simulate retail conditions, or placed directly
      at 20 degrees C. All formulations significantly reduced decay in all cultivars.
      Switch, Signum and Folicur were the most active, while Score was slightly less
      effective. Teldor activity was low, especially in Thyrintos apricots, where the
      percentage of rotten fruit was slightly lower than in control fruit. Brown rot
      was the most representative disease, but in apricots a high percentage of fruit
      was affected by blue mold and grey mold. Rhizopus rot generally developed as a
      secondary disease on fruit previously affected by other pathogens and was more
      frequent in control and Teldor treated fruit. Preharvest sprays with Signum 3
      days before harvest reduced postharvest decay after 1 week storage at 20 degrees
      C in Glo haven peaches and Venus nectarine harvested at advanced stage of
      maturity. Combining pre-harvest sprays with Signum and a 2-min postharvest dip in
      2% sodium bicarbonate at 20 degrees C further reduced decay. In Sothern regions
      of Italy, the use of synthetic fungicides only immediately before harvest in
      years when the weather conditions are not favorable to brown rot and other
      pathogens inducing postharvest decay, combined with a postharvest treatment with
      sodium bicarbonate could be a feasible integrated approach to reduce the risk of
      selection of resistant strains of fungi to synthetic fungicides while controlling
      effectively postharvest decay.

PMID- 23878975
TI  - Individual and combined effects of postharvest dip treatments with water at 50
      degrees C, soy lecithin and sodium carbonate on cold stored cactus pear fruits.
AB  - Objective of this study was to evaluate the effect of prestorage dip treatments
      at 20 degrees C or 50 degrees C alone or with sodium carbonate (SC) and soy
      lecithin (LEC), either individually or in combination, on weight losses, peel
      disorders, overall appearance and decay of cactus pears. Fruits were subjected to
      a simulated Mediterranean fruit fly (medfly) disinfestation by cold quarantine at
      2 degrees C for 21 days followed by one week of shelf-life at 20 degrees C. Hot
      water alone was very effective in reducing peel disorders and decay both during
      cold storage and shelf-life. SC applied at 20 degrees C showed a weak control of
      decay and chilling injury, while its effectiveness significantly increased when
      the solution temperature was set to 50 degrees C. LEC was more effective in
      preserving freshness during cold storage, but after shelf-life decay incidence in
      fruit dipped in LEC at 20 degrees C or 50 degrees C was higher than in those
      dipped in water at 20 degrees C or 50 degrees C, respectively. Significant but
      moderate differences were detected among treatments in weight loss. After shelf
      life, fruit dipped in the heated mixture of SC and LEC showed the lowest
      incidence of peel disorders and the highest percentage of marketable fruit,
      although decay incidence was slightly higher than in fruit treated with SC at 50
      degrees C. SC and LEC used in combination at 50 degrees C improved fruit
      tolerance to chilling injury and reduced decay.

PMID- 23878976
TI  - Effect of acetic acid repeated treatments on post-harvest quality of "Taloppo"
      table grape.
AB  - The most important pathogen for table grapes is Botrytis cinerea which causes a
      rapid deterioration of fruit. Postharvest losses are controlled with SO2
      fumigations carried out every 7 or 10 days, but the use of this gas is becoming
      more difficult to justify because of undesirable effects on the fruit and the
      increasing concern for human health. Acetic acid, classified as a GRAS compound,
      can be employed with no restriction as preservative and represents a possible
      substitute to sulphur dioxide. The aims of the present work were: (1) to evaluate
      if repeated treatments with AAC during storage preserve table grapes fruit
      quality; (2) to verify the effectiveness of 3 different concentrations and time
      intervals between each treatment and compare the effects with SO2 treatment; The
      amounts of AAC used in each fumigation, performed for 15 minutes, were 30, 50 and
      75 microL/L, and treatments were carried out 5, 3 and 2 times respectively during
      storage, in order to have the same final concentration (150 microL/L). Table
      grapes were also fumigated with SO2. Fruit was stored for 8 weeks at 5 degrees C
      and 95% of RH, followed by 4 days of a simulated shelf-life (SSL) at 20 degrees C
      and 85% RH. At the end of experiment decay, weight loss and visual assessment
      were evaluated. After eight weeks of storage the incidence of grey mould, with
      respect to untreated fruit, was reduced in all treatments. The comparison among
      the different treatments did not show significant differences between the
      fumigations performed 3 and 2 times, with 24.9% and 27.2% of rots respectively. A
      better decay control was achieved with 5 fumigations carried out every 2 weeks,
      (18.1% of rots), while decay in fruit treated with SO2 was 26.2%. During the SSL
      period no particular differences were observed among all treatments. None of the
      treatments affected weight loss, as well as no differences were found in the
      score attributed for the external quality (rachis browning and berries
      appearance). The results showed that a good control of grey mould could be
      achieved on table grapes by repeated fumigations during storage. AAC could be a
      promising compound to be used as alternative to SO2 in keeping fruit quality.

PMID- 23878977
TI  - Isolation and partial characterization of culturable endophytic Arthrobacter spp.
      from leaves of maize (Zea mays L.).
AB  - The presence and diversity of the endophytic Arthrobacter species are relatively
      uninvestigated. We determined the genotypic and physiological diversity of the
      endophytic Arthrobacter spp. isolated from the interior leaf tissues of four out
      of six maize cultivars tested, all of which were collected under field
      conditions. Strains A7 and A9 isolated from Krol cultivar and strain A23 isolated
      from KB1902 cultivar were identified as A. nicotinovorans. Strains A18, A22 and
      A34 identified as A. nitroguajacolicus were isolated from KB1903, KB1902 and
      Cyrkon cultivars respectively. Isolated strains tolerate the presence of o
      coumaric, p-coumaric, chlorogenic, and ferulic acids in a concentration of at
      least two times higher than naturally occurring in maize tissue. The presence of
      the nitrogenase reductase gene nifH, a marker of biological nitrogen fixation,
      was determined in only two strains of A. nitroguajacolicus A18 and A34. None of
      the tested strains released compounds inhibiting in vitro the growth of the fungi
      Fusarium moniliforme and F. graminearum, pathogenic to maize. Seed inoculations
      with the A. nicotinovorans strain A7 suppressed the development of seedlings of
      four maize cultivars, which were not colonized by this species of bacteria, but
      stimulated the development of seedlings of the host-cultivar Krol. Also, the A.
      nitroguajacolicus strain A18, which was applied as seed treatment, suppressed the
      development of seedlings of three maize cultivars, which were not colonized by
      this species of bacteria. The occurrence of endophytic A. nicotinovorans and A.
      nitroguajacolicus inhabiting interior tissues of maize leaves of specific maize
      cultivars is a first report in literature.

PMID- 23878978
TI  - Compost suppressiveness against Phytophthora spp. on Skimmia japonica and azalea.
AB  - Suppression of soil-borne plant diseases with composts has been widely studied.
      Composts have been found to be suppressive against several soil-borne pathogens
      in various cropping systems. Ornamental plants are generally cultivated in pots,
      allowing the use of suppressive substrates to control zoospore-producing
      pathogens, like Phytophthora sp. The objective of the present work was to assess
      compost suppressiveness against Phytophthora cinnamomi on Rhododendron spp., and
      against Phytophthora nicotianae, an emerging pathogen on Skimmia japonica. A
      municipal compost that showed a good suppressive activity in previous trials on
      vegetable crops was used. Compost was mixed at 10, 20 e 40% (v/v) with a
      commercial peat substrate, used as control. Substrates have been inoculated at
      1g/l dosage of wheat and hemp kernels of Phytophthora spp. and after one week 15
      20 plants were transplanted for each treatment in 2 liters volume pots and placed
      in greenhouse at 20 degrees C. A chemical control (Metalaxil-M) was also used.
      Diseased plants were assessed weekly after transplanting and above-ground biomass
      of plants was assessed at the end of the trials. Results showed a significant
      disease control when compost was used at 20-40% on S. japonica, without showing
      any phytotoxic effect. Disease suppression was shown at 40% on azalea, but
      compost was slightly phytotoxic on plants. The use of compost based substrates
      can be a suitable strategy for controlling soil-borne diseases on ornamentals,
      but results depend also on alkalinity tolerance of plants.

PMID- 23878979
TI  - Effect of climate change on Alternaria leaf spot of rocket salad and black spot
      of basil under controlled environment.
AB  - Plant responses to elevated CO2 and temperature have been much studied in recent
      years, but effects of climate change on pathological responses are still largely
      unknown. The pathosystems rocket (Eruca vesicaria subsp. sativa)--Alternaria leaf
      spot (Alternaria japonica) and basil (Ocimum basilicum)--black spot
      (Colletotrichum gloeosporioides) were chosen as models to assess the potential
      impact of increased CO2 and temperature on disease incidence and severity under
      controlled environment. Potted plants were grown in phytotrons under 4 different
      simulated climatic conditions: (1) standard temperature (ranging from 18 degrees
      to 22 degrees C) and standard CO2 concentration (400 ppm); (2) standard
      temperature and elevated CO2 concentration (800 ppm); (3) elevated temperature
      (ranging from 22 degrees to 26 degrees C, 4 degrees C higher than standard) and
      standard CO2 concentration; (4) elevated temperature and CO2 concentration. Each
      plant was inoculated with a spore suspension containing 1 x 10(5) cfu/ml of the
      pathogen. Disease incidence and severity were assessed 14 days after inoculation.
      Increasing CO2 to 800 ppm showed a clear increment in the percentage of
      Alternaria leaf spot on rocket leaves compared to standard conditions. Basil
      plants grown at 800 ppm of CO2 showed increased black spot symptoms compared to
      400 ppm. Disease incidence and severity were always influenced by the combination
      of rising CO2 and increased temperature, compared to standard conditions (400 ppm
      of CO2 - 22 degrees C). Considering the rising concentrations of CO2 and global
      temperature, we can assume that this could increase the severity of Alternaria
      japonica on rocket and Colletotrichum gloeosporioides on basil.

PMID- 23878980
TI  - Endophytic fungi isolated from wheat (Triticum durum Desf.): evaluation of their
      antimicrobial activity, antioxidant activity and host growth promotion.
AB  - The emergence of antibiotic-resistant micro-organisms calls for inventive
      research and development strategies. The screening for antimicrobial compounds
      from endophytes is a promising way to meet the increasing threat of drug
      resistant strains of human and plant pathogens. Endophytes may be defined as
      "microbes that colonize living, internal tissues of plants without causing any
      immediate, overt negative effects". Endophytes are relatively unstudied as
      potential sources of novel natural products for exploitation in medicine,
      agriculture, and industry. The purpose of this study was to evaluate several
      isolated fungi from wheat (Triticum durum Desf.) Mohamed Ben Bachir variety and
      to select endophytic fungi for further evaluation of its antimicrobial,
      antioxidant activities and host growth promotion. A total of 20 endophytic fungi
      have been isolated. Antimicrobial activity was evaluated for crude ethyl acetate
      extracts using an agar diffusion assay. All extracts showed inhibitory activity
      on at least one or more pathogenic microorganism, with an average zone of
      inhibition varied between 7 mm to 25 mm, a large zone of 23 and 25mm against
      candida albicans and Escherichia coli respectively. The antioxidant capacity of
      the extracts was evaluated by beta-carotene/linoleic acid assay. Results showed
      that 70% of these extracts have antioxidant activity, exhibiting 50, 57% to 78,
      96% inhibitions. While 30% from them, their inhibitory activity for oxidation of
      linoleic acid Were less than 50%. Growth promotion ability of these endophytes
      was tested on seed germination among ten isolates tested, two isolates showed
      significant growth promotion effects on wheat seeds. From the present work we can
      conclude that these microorganisms could be promising source of bioactive
      compounds, growth promotion and warrant further study.

PMID- 23878981
TI  - Streptomycetes and micromycetes as perspective antagonists of fungal
      phytopathogens.
AB  - Among natural factors that permanently influence on the plants, the soil
      microorganisms play a special role for the growing of plants as habitants of
      their rhizosphere. Mainly they are the representatives of actinomycetes genus
      Streptomyces and fungal genus Penicillium and their metabolic products stimulate
      plant growth and inhibit the growth of pathogenic fungi and bacteria. The aim of
      our study was to determine the antagonism of actinomycetes and micromycetes
      isolated from soils of R. Moldova against the fungal pathogens of agricultural
      plants. The strains were isolated from 5 types of chernozem (black soil) from
      central zone of R. Moldova, with different concentration of humus. Most of
      micromycetes and streptomycetes were isolated from soil sample 1 (monoculture of
      maize) and soil sample 2 (Poltava road border) with similar humus content (2.4
      2.6%). The antifungal activity of micromycetes strains was occurring mostly
      against Fusarium solani and Thelaviopsis basicola, at streptomycetes against
      Alternaria alternata and Botrytis cinerea. It was revealed the strains completely
      inhibit the growth of Alt. alternata (streptomycetes strains 23, 33, 37), B.
      cinerea (Streptomyces sp. 17), and F. solani (Penicillium sp. 104). Our results
      allow to consider the actinomycetes Streptomyces sp.9, Streptomyces sp. 12,
      Streptomyces sp. 17, Streptomyces sp. 37 Streptomyces sp. 66 and micromycetes
      Penicillium sp. 5, Penicillium sp. 65, Penicillium sp. 104 isolated from soils of
      R. Moldova, as prospective strains-antagonists against the phytopathogenic
      fungus, the causative agents of agricultural plants deseasis.

PMID- 23878982
TI  - The antagonism activity of bacteria isolated from potato cultivated soil.
AB  - Soil-borne fungal and bacterial root pathogens can cause serious losses to
      agricultural crops. Resistant plant varieties are not available for several soil
      borne pathogens and chemical control is often insufficiently effective in soil.
      The enhancement of disease suppressive properties of soils will limit disease
      development, thus, being of great importance for sustainable agriculture as well
      as organic farming systems. The aim of this research is to find and identify
      suppressive soils in the Setif's areas (potato field located in different regions
      of Setif); this allows the selection of the indigenous soil bacteria that are
      able to develop several mechanisms of action related to biocontrol of
      phytopathogenic fungi affecting potato crops. Among 50 bacterial strains only 14
      showed a wide range of antifungal action against the tested phytopathogenic
      fungi. With a range of inhibition percent from 0 to 92.30% especially Fusarium
      oxysporum f. sp. albedinis with 92% inhibition.

PMID- 23878983
TI  - Prevalence of Erwinia soft rot affecting cut foliage, Dracaena sanderiana
      ornamental industry and solution towards its management.
AB  - The study was carried out under net house conditions at Green Farms Ltd, Marawila
      to determine the occurrence and severity of Erwinia soft rot disease in Dracaena
      sanderiana plants and to formulate the possible control measures. Field
      experiment was carried out to manage the soft rot disease in D. sanderiana
      plants. Three different soil treatments with vermicompost, cow dung and poultry
      manure were tested to manage the disease and plots without application were kept
      as control. Percent disease incidence, disease reduction and growth parameters
      were recorded and data were statistically analyzed. Higher percentage of disease
      reduction was observed in vermicompost (80%) treated plots than those with cow
      dung (60%) and poultry manure treated. Sprinkler application of water was found
      favorable to spread soft rot disease and watering through horse pope had lessened
      the disease incidence significantly. Moreover plant height, shoot and root
      biomass, number of leaves per plant, leaf length and leaf width were
      significantly high in vermicompost media. Weeding, removal of diseased leaves and
      plants, and avoiding sprinkler irrigation were helpful to reduce the disease
      spread from plant to plant. Vermicompost is the best substrate for suppression of
      the disease and promoting the growth of plant. Among the different water
      management practices tested to reduce the disease severity of Erwinia soft rot
      disease in D. sanderiana plants, water irrigated through the horse pipe was
      effective compare to sprinkler application. In-vitro experiment conducted to
      manage the Erwinia soft rot disease by using bio-agent, Pseudomonas fluorescens
      was found effective to reduce the growth of Erwinia under in-vitro conditions.

PMID- 23878984
TI  - Introduction of some important antagonistic bacteria affecting on damping-off of
      canola.
AB  - Three hundred ninety five bacterial isolates were collected from canola Root and
      Rhizosphere in Golestan, Mazandaran, Guilan and Tehran provinces. At first,
      antagonistic effect of bacterial isolates on Rhizoctonia solani was studied using
      dual culture test assay. The results showed that 60 isolates had the ability to
      inhibit the growth of fungi on PDA medium. On the basis of the biochemical,
      physiological and morphological tests, isolates Pf41, Pf51, Pf411 and Pf412 were
      identified as Pseudomonas fluorescens, isolate Bu1 as Burkholderia cepacia, the
      isolates B1, B2, Bs44 and B6 were as Bacillus subtilis and S44, str45 as
      Streptomyces sp. Results of the studies on biocontrol mechanism showed that
      Isolates produced antibiotics and volatile metabolites that prevented the
      mycelial growth of the fungus. Also the isolates produced some of antimicrobial
      metabolites including hydrogen cyanide, protease and siderophore. Isolates effect
      inhibition of in vitro growth of the fungus. The effect of isolates on disease
      reduction in compare with control have significantly differentiated. None of the
      isolates were able completely to prevent disease occurrence. Isolates applied as
      soil treatment had a significantly higher disease control as compared to seed
      treatment. Isolates had considerable effect on reduction disease under the
      greenhouse conditions.

PMID- 23878985
TI  - Wheat Mycosphaerella graminicola interactions in Morocco.
AB  - Mycosphaerella graminicola is nowadays one of the most important foliar pathogens
      on wheat crops worldwide and more specifically in Morocco. The interactions of
      eight monoconidial isolates of this fungus, sampled in different regions of
      Morocco, with 3 Moroccan wheat cultivars (Massira, Amal and Arrihan) differing in
      their resistance level to the pathogen, were studied using artificial
      inoculations in the greenhouse. Disease notations (percentage of third leaf areas
      covered by lesions bearing pycnidia) at 21 days post inoculation revealed
      significant differences among the different isolate-cultivar combinations. Most
      isolates expressed pathogenicity profiles in accordance with the resistance
      levels of the cultivars studied. However, T01701 showed a similar pathogenicity
      level on the three cultivars and T01718 induced more disease on the moderately
      resistant cv. Amal compared to the susceptible cv. Massira and the resistant cv.
      Arrihan, respectively. Furthermore, the infection process of the isolate T01757
      was investigated at 4, 8, 12, 16 and 21 days post-inoculation. This isolate
      exhibited a disease gradient (65%, 24% and 5%) which negatively correlated with
      the resistance levels of the cultivars. No significant differences were obtained
      regarding the rates of spore germination and leaf penetration events. However,
      rates of mesophyll colonization positively correlated with the disease levels
      scored on the cultivars. This study supports the presence of strain-cultivar
      interactions between wheat and M. graminicola in Morocco and confirms the
      importance of mesophyll colonization in disease establishment and extension.

PMID- 23878986
TI  - The peculiarities of winter wheat eyespot management under Lithuanian conditions.
AB  - Research evidence suggests that in Lithuania eyespot incidence in winter wheat
      crops was from 33 to 60% annually. Climatic conditions are the most important
      factor influencing the infection of winter wheat by eyespot. The variation of the
      climatic conditions (rainfall and number of rainy days) in the autumn and spring,
      the incidence and disease severity index (DSI%) of eyespot in winter wheat were
      mathematically described by a linear regression. The amount of rainfall during
      the autumn and spring periods until winter wheat second node stage (15 May) and
      eyespot incidence at soft dough stage showed a strong statistically significant
      liner correlation R = 0.789 (P < or = 0.01). During the summer period the amount
      of rainfall showed a moderate statistically significant liner correlation with
      disease severity index (DSI%) R = 0.550 (P < or = 0.05). To ascertain the
      necessity of fungicide use for eyespot control in winter wheat crops under
      Lithuanian conditions, field experiments were conducted over the 2008-2011
      period. A significant reduction in the disease incidence and severity resulting
      from fungicide application was established only in 2010, when eyespot infection
      level was the highest. This was determined by one third higher precipitation in
      the autumn and spring of that year and significantly higher number of rainy days
      compared with other years.

PMID- 23878987
TI  - Cultural characteristics of Sporisorium sorghi and detection of the pathogen in
      plant tissue by microscopy and PCR.
AB  - Despite the economic importance of covered kernel smut of sorghum (Sporisorium
      sorghi) in many African states and other parts of the world, only limited
      information is available on laboratory cultivation methods for this fungus and
      techniques for its diagnosis in plant tissue. When in the present study spores of
      S. sorghi were kept as intact sori at 5 degrees C, 80% of the spores germinated
      even after 24 months of storage. Spore germination on agar medium and production
      of mycelial dry weight in still culture were highest between 20 and 35 degrees C,
      with a peak at 30 degrees C. Both showed a steady increase from pH 4.5 to pH 7.5,
      followed by a decline at pH 8.5 and 9.5. In shake culture in different broth
      media the addition of 0.3% peptone from soybean caused an increase in fungal
      growth compared to the media alone. Of the media tested, mycelial production was
      highest in malt dextrose broth supplemented with peptone. When cultivated on
      different agar media, the morphology of single spore isolates differed both among
      isolates and depending on the agar medium. In greenhouse experiments, five short
      heighted, early maturing sorghum breeding accessions proved to be partially or
      fully resistant to covered kernel smut. Among the plant material tested, cv.
      'Dorado' appeared to be the one best suited for greenhouse experiments with
      covered kernel smut. By microscopy of hand-cut sections stained with trypan-blue,
      hyphae of S. sorghi were seen in apical buds and in nodes of young sorghum
      plants. Diagnostic PCR amplified a 903 bp element comprising the internal region
      of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) encoding gene and enabled
      the detection of S. sorghi in both nodes and apical buds of infected sorghum
      seedlings. Both techniques, i.e. microscopy and diagnostic PCR have the potential
      to be used in studies for the identification of effective sorghum seed treatments
      already at the seedling stage.

PMID- 23878988
TI  - The origin of metamitron resistant Chenopodium album populations in sugar beet.
AB  - Chenopodium album L. is a major weed in spring-planted crops in the temperate
      regions of the world. Since 2000, farmers have reported an unsatisfactory control
      of this weed in sugar beet fields in Belgium, France and The Netherlands.
      Frequently, the surviving C. album plants are resistant to metamitron, a key
      herbicide in this crop. Metamitron resistance in C. album is caused by a Ser264
      to Gly mutation in the psbA gene on the chloroplast genome, which prevents
      binding of metamitron to its target site. This mutation causes also resistance to
      other herbicides with a similar mode of action, like metribuzin -applied in
      potato- and atrazine in particular. Atrazine has been applied very frequently in
      maize in the 1970s and the 1980s, but is now banned in Europe due to
      environmental reasons. The persistent use of atrazine in maize confronted Belgian
      and other European farmers in the early 1980s with atrazine resistant C. album
      with the same Ser264 to Gly mutation. The problems with atrazine resistant C.
      album disappeared when other herbicides were applied in maize. Unfortunately,
      this is not the case for metamitron resistant C. album in sugar beet, because no
      replacement herbicide is readily available. The history of atrazine use in maize
      brought up a question concerning the origin of the current metamitron resistant
      C. album populations. Have these populations been selected locally by regular use
      of metamitron in sugar beet or did the selection occur earlier by atrazine use
      when maize was grown in the same fields? This would have serious implications
      regarding the reversibility of herbicide resistance. Therefore, soil samples were
      collected on 16 fields with different histories: five fields with an organic
      management over 25 years, two fields with a history of atrazine resistant C.
      album, five fields with metamitron resistant C. album in sugar beet and four
      fields which were under permanent grassland for 10 years, preceded by a regular
      rotation in which sugar beet was a key crop. The seeds of C. album were extracted
      from the soil and germinated on a germination table. Germinated seeds were
      allowed to grow in a growth chamber. Metamitron resistance was determined by a
      chlorophyll fluorescence test and leaf material was sampled for AFLP-analysis.
      For all fields, estimations were made of the size of the seed bank (i.e. an
      indirect estimate of population size), the frequency of resistant plants and the
      genetic diversity of resistant and susceptible populations. The results indicate
      that herbicide-resistant C. album populations are persistent and maintain their
      adaptive capacity, challenging future management of metamitron resistant C.
      album.

PMID- 23878989
TI  - Maleic hydrazide: sprout suppression of potatoes in the field.
AB  - In 2005, the active substance maleic hydrazide was released on the Belgian
      market. Maleic hydrazide is authorized in potatoes as foliar treatment for
      instore sprout suppression and control of volunteers. The mode of action is based
      on blocking cell division whilst cell elongation is not affected. The product
      must be applied at once during the growing season, only after at least 80% of the
      tubers have reached 25 mm diameter and not later than 3 weeks before haulm
      killing. The first 24 h after application, no meaningful precipitation should
      occur to insure sufficiently uptake of the product by the crop. Field trials were
      set up for 4 years (2005-2008) and 4 locations per year with application of
      maleic hydrazide in four different cultivars (Bintje, Fontane, Asterix and
      Cilena). After application, the cultivar Asterix showed almost every year a
      temporarily phytotoxicity (bronze discoloration). On the first place yield was
      determined. When maleic hydrazide was applied too early (80% tubers % 25mm
      diameter) yield was negatively affected (3 years on 4) except for the cultivar
      Cilena (fresh market). Internal quality (dry matter and fry quality) was not
      influenced by the application of maleic hydrazide. Only Fontane had a slightly
      lower dry matter content. Maleic hydrazide also influenced appearance of
      secondary growth. However, the results were very variable depending on cultivar,
      location and time of application. After harvest, the tubers were kept in storage
      and assessed monthly on germination. Potatoes treated late in the growing season,
      showed a shorter dormancy period. A part of the tubers was replanted the
      following spring to verify volunteer control. Additional trials were set up by
      the Flemish government for two years (2010-2011). The results of previous trials
      were confirmed. Additional, the influence of maleic hydrazide on internal
      germination during storage was examined on the cultivar Innovator. The tests
      clearly showed a positive effect for this parameter.

PMID- 23878990
TI  - Sensitivity of locally naturalized Panicum species to HPPD- and ALS-inhibiting
      herbicides in maize.
AB  - Until recently the Panicum species Panicum schinzii Hack. (Transvaal millet),
      Panicum dichotomiflorum Michx. (Fall panicum) and Panicum capillare L.
      (Witchgrass) were completely overlooked in Belgium. Since 1970, these species
      have gradually spread and are now locally naturalized and abundant in and along
      maize fields. One of the possible raisons for their expansion in maize fields
      might be a lower sensitivity to postemergence herbicides acting against panicoid
      grasses, in particular those inhibiting 4-hydroxyphenyl pyruvate dioxygenase
      (HPPD) and acetolactate synthase (ALS). A dose-response pot experiment was
      conducted in the greenhouse to evaluate the effectiveness of five HPPD-inhibiting
      herbicides (sulcotrione, mesotrione, isoxaflutole, topramezone, tembotrione) and
      two ALS-inhibiting herbicides (nicosulfuron, foramsulfuron) for controlling
      Belgian populations of P. schinzii, P. dichotomiflorum and P. capillare. Shortly
      after sowing, half of all pots were covered with a film of activated charcoal to
      evaluate foliar activity of the applied herbicides. In another dose-response pot
      experiment, sensitivity of five local P. dichotomiflorum populations to HPPD
      inhibitors and nicosulfuron was investigated. Finally, the influence of leaf
      stage at time of herbicide application on efficacy of topramezone and
      nicosulfuron for Panicum control was evaluated. Large interspecific differences
      in sensitivity to HPPD-inhibiting herbicides were observed. Panicum schinzii was
      sensitive (i.e., required a dose lower than the maximum authorized field dose to
      achieve 90% reduction in biomass) to tembotrione but moderately sensitive (i.e.
      required maximum field dose) to topramezone and poorly sensitive (i.e. required
      three-fold higher dose than maximum field dose) to mesotrione and sulcotrione.
      However, P. dichotomiflorum, a species that morphologically closely resembles P.
      schinzii, was sensitive to mesotrione and topramezone but moderately sensitive to
      tembotrione. All Panicum species were sensitive to low doses of nicosulfuron and
      foramsulfuron. The relative contribution from soil activity to weed control
      resulting from postemergence applications was important for isoxaflutole,
      sulcotrione, tembotrione and mesotrione but not for topramezone, nicosulfuron and
      foramsulfuron. Naturalized Panicum dichotomiflorum populations exhibited
      differential herbicide sensitivity profiles. Panicum schinzii, P. capillare and
      P.dichotomiflorum showed a progressive decrease in sensitivity to topramezone and
      nicosulfuron during seedling development. A satisfactory postemergence control of
      Panicum species in the field will require appropriate choice of herbicide and
      dose, as well as a more timely application (i.e. before weeds reach the four
      leaves stage).

PMID- 23878991
TI  - Effect of mechanical weeding on wild chamomile (Matricaria chamomilla L.)
      populations in winter wheat crop (Triticum aestivum L.).
AB  - Currently, economic, agronomic and environmental concerns lead to reduce the use
      of herbicides. Mechanical weeding can help to reach this objective. Dynamics and
      biology of wild chamomile (Matricaria chamomilla L.) populations were assessed as
      well as dynamic of winter wheat (Triticum aestivum L.) for four level of
      application of a weeder-harrow (0, 1, 2, 3 treatment(s)). After each treatment,
      an effect of mechanical weeding on wild chamomile density was observed. Density
      of wild chamomile decreased significantly with intensification of mechanical
      weeding. A third treatment allowed eliminating late emerged plants.

PMID- 23878992
TI  - Changes in dicot-weeds species composition in spring barley in Latvia during the
      past 20 years.
AB  - Dicot weed populations were assessed in spring barley trials carried out in four
      three-years periods at 5-year intervals: 1990-1992, 1995-1997; 2001-2003 and 2006
      2008. The overall aim of this research was to evaluate the changes in dicot-weed
      infestations in spring barley in fields of one region (Riga) of Latvia in sod
      podzolic loamy sand soil. The results of the trials showed that Galeopsis spp,
      Stellaoria media, Viola orvensis and Chenopodium album were among the most
      frequent weed species in the periods of 1990-1992 and 1995-1997. The occurrence
      of C. album and V. arvensis increased during the periods of 2001-2003 and 2006
      2008.

PMID- 23878994
TI  - Finance: trusts risk unwanted legacy with short-term approach to savings.

PMID- 23878993
TI  - Low-impact chemical weed control techniques in UNESCO World Heritage Sites of
      Cuba.
AB  - Dichrostachys cinerea is a thorny, acacia-like, fast-growing woody bush which
      invades fields, wasteland, road sides and other disturbed areas. This gregarious
      species has become a very aggressive invasive weed in Cuba, where no native
      predators or pathogens are found. It often encroaches in fallows, overgrazed
      areas and mismanaged veld. D. cinerea is a very difficult weed to eliminate
      because of its active suckering, and is liable to produce dense thickets which
      are quite impenetrable on account of the density and abundance of its long,
      stiff, sharp thorns. In the Valle de los Ingenios area (Cuba Central), the tree
      is unchecked and forms veritable forests in areas on which cane growing has been
      discontinued. Physical management by cutting and burning the plants is not a very
      efficient control method, since the seeds survive in the soil, and they grow very
      fast. Therefore, chemical methods via the use of herbicides are often necessary
      to eradicate this weed. A preliminary study using glyphosate and auxin-like
      herbicides (2,4-D + picloram, MCPA, and MCPA + 2,4-D) plus adjuvants has been
      carried out in order to elucidate the best mixtures rendering maximum weed
      control with minimum herbicide rate and environmental stress. None of the
      herbicides used except glyphosate and 2,4-D + picloram showed acceptable
      mortality rates (75-80%) at the recommended doses tested. In the failed herbicide
      treatments, only the use of double herbicide rates succeeded in controlling
      marabou. The herbicide mixture of 2,4-D + picloram formulated with either a non
      ionic surfactant or a mixture of fatty acid esters was the best option to control
      D. cinerea in terms of maximum effectiveness and minimum environmental stress, as
      the reduction in active ingredients applied to the environment was x3 in these
      two adjuvant-amended formulations compared to 2,4-D + picloram alone.

PMID- 23878995
TI  - Trusts shyfrom pay savings, analysis shows.

PMID- 23878996
TI  - Changing the culture of the NHS: enough words, we need more action.

PMID- 23878997
TI  - Staff wellbeing is vital.

PMID- 23878998
TI  - Duty of candour: it's a mistake to legislate for a culture of openness.

PMID- 23878999
TI  - Exporting innovation: part 1 of 2 take NHS expertise east.

PMID- 23879000
TI  - Commissioning: growing public engagement.

PMID- 23879001
TI  - Community services: Why death should be brought into the open.

PMID- 23879002
TI  - [Comparison of the prevalence frequency of infectious skin changes in dialyzed
      patients and after kidney transplantation].
AB  - Due to graft preserving immunosuppressive therapy, renal transplant recipients
      are predisposed to the development of a variety of skin infections and skin
      cancers. The aim of the study was to compare prevalence frequency of infective
      skin changes among patients after kidney transplantation and the dialyzed
      population. Clinical dermatological examination was performed in 486 patients
      after renal transplantation. The group consisted of 296 men (60.9%) and 190 women
      (30.1%), of mean age 46.1+/-13.1 (18-74 years) with median time after
      transplantation of 74.3+/-52.1 months. Most of the patients (80.7%) before
      transplantation were treated by maintenance hemodialysis. The most frequent
      immunosuppression regiments were combination of cyclosporine A (CsA) with
      mycofenolate mofetil (MMF) and steroids (GKS)-207 patients (42.5%); tacrolimus
      (TAC) with MMF and GKS-102 (20.9%) and CsA with azathiopine and GKS-53 patients
      (10.9%). The group of 112 dialyzed patients consisted of: 57 males (50.9%) and 55
      females (49.1%), aged 57.4+/-15.4 years without history of immunosuppressive
      therapy and were on maintenance dialysis for 63.2+/-74.0 months. Most of this
      group (77.7%) was on maintenance hemodialysis, while the remaining 22.3% on
      peritoneal dialysis. The obtained results were analyzed based on t-Student's,
      Mann-Whitney's, chi-square and Fisher tests. It was shown that infective skin
      changes were significantly more frequent in the group of patients after kidney
      transplantation as compared with the dialyzed population. They were observed in
      53.9% and 9.8% of the studied populations, respectively (p<0.0001). In the
      studied group after kidney transplantation the most frequent were viral changes
      (38.9%). Fungal infection was observed in 25.9% of these patients, while
      bacterial in 1.2% of this study group. In the dialyzed population fungal
      infections were diagnosed in 8.9%, while viral in 3.6% of patients. No bacterial
      changes were observed in this group. Acne was observed in 16.5% of patients after
      kidney transplantation. CONCLUSIONS: 1. In the group of patients after kidney
      transplantation receiving immunosuppressive therapy viral, fungal and bacterial
      infective skin changes were significantly more frequent as compared with the
      dialyzed patients. 2. The most frequent skin changes observed in patients after
      kidney transplantation were viral warts.

PMID- 23879003
TI  - [Involvement of endogenous tachykinins in the development of jejunal mucosa
      injury induced by on-steroidal anti-inflammatory drugs].
AB  - Previous studies have shown that tachykinins, the largest family of
      neuropeptides, affect the development of mucosal damage in the stomach and colon.
      The aim of the study was to assess the influence of tachykinins receptors
      antagonists on the development of the mucosa injury in the proximal and distal
      jejunum. MATERIAL AND METHODS: Mucosal damage was induced by administration of
      non-steroidal anti inflammatory drugs (NSAIDs), indomethacin, celecoxib or
      combination of indomethacin plus celecoxib given intragastrically. NK-1 receptor
      antagonist (SR 140333), NK-2 receptor antagonist (SR 48968) and NK-3 receptor
      antagonist (SR 142801) were administered intraperitoneally twice, 30 min before
      treatment with NSAID and again 24 h later, 30 min before the end of the
      experiment. RESULTS: Administration of indomethacin, a relatively selective
      inhibitor for cyclooxygenase-1 (COX-1), induced mucosal lesions in the jejunum.
      Lesions area in the distal jejunum was 8-fold bigger than in the proximal
      jejunum. This effect was associated with a significant reduction in mucosal blood
      flow and an increase in mucosal concentration of pro-inflammatory interleukin
      1beta (IL-1beta). Celecoxib, selective inhibitor for COX-2 failed to induce
      mucosal lesions and did not affect the mucosal blood flow and IL-1beta
      concentration in the proximal and distal jejunum. In rats treated with a
      combination of indomethacin plus celecoxib, ulcers reached maximal area. This
      effect was associated with the highest concentration of mucosal IL-1beta and
      maximal reduction in mucosal blood flow. Administration of NK-1 receptor
      antagonist, SR 140333 reduced jejunal damage induced by indomethacin given alone
      or in combination with celecoxib. This effect was associated with significant
      reduction in mucosal concentration of IL-1beta. Effect of SR 140333 on mucosal
      blood flow was statistically insignificant. Neither NK-2 nor NK-3 receptor
      inhibitor affected mucosal blood flow, IL-1beta concentration area of NSAIDs
      induced mucosal damage in the jejunum. CONCLUSIONS: Blockade of NK-1 receptor
      protects the jejunum against NSAIDs-induced mucosal injury and reduces local
      inflammation. This observation indicates the involvement of endogenous
      tachykinins in deleterious effects of NSAID.

PMID- 23879004
TI  - [Staging of thyroid cancer--comparison of cases diagnosed preoperatively versus
      incidentally after surgery for benign goiter].
AB  - INTRODUCTION: The aim of this study was to compare staging of incidentally
      diagnosed thyroid cancer (TC) to staging of preoperatively suspected TC. METHODS:
      This was a retrospective study of 224 patients who underwent surgery for primary
      TC between 2009 and 2011. Clinical and pathological data included in the TNM and
      AJCC staging system (7th edition, 2010) were analysed. Staging of incidentally
      diagnosed TC was compared to staging of preoperatively suspected TC. RESULTS:
      Suspicion of TC was made before surgery in 57.6% patients, and in 42.4% patients
      TC was diagnosed postoperatively. Papillary TC was predominant and followed by
      follicular TC, which were suspected in 88.4% and 4.7% of patients before surgery,
      and were diagnosed in 77.9% and 16.8% of patients postoperatively (p=0.035 and
      p<0.001, respectively). Preoperatively diagnosed TC was predominant in patients
      below 45 years of age (64.3% vs. 25.3%; p<0.001), was at lower stage at the
      diagnosis (according to AJCC in stage I : 42.6% vs. 67.4%; p<0.001; in stage II:
      6.2% vs. 12.6%; p=0.095; in stage III: 38.0% vs. 16.8%; p<0.001; in stage IV:
      13.2% vs. 3.2%; p=0.009, respectively), and it was more common multicentric
      (29.5% vs. 9.5%; p<0.001) than incidental TC. CONCLUSIONS: Approximately 40% of
      cases of TC is diagnosed incidentally based on postoperative pathology report.
      Incidental TC is predominant below age 45 years, is revealed with early-stage
      more common than TC diagnosed preoperatively, and occurs multicentric less
      frequently.

PMID- 23879005
TI  - [Prevention of atherosclerosis in children--the role of statins and aspirin].
AB  - Cardiovascular diseases remain the leading cause of death in Poland and in
      Europe. Children rarely suffer from them, although most of the risk factors which
      accelerate progression of atherosclerosis commence in childhood, including:
      dyslipidemias, hypertension, diabetes, and obesity. Moreover during last few
      years the incidence of some of risk factors in children, such as obesity,
      diabetes and dyslipidemia has increased significantly. It is known from the
      autopsy studies that atherosclerosis can be identified at very young age in
      healthy children. In adult population medications such as HMG-CoA reductase
      inhibitors (statins) and acetylsalicylic acid (ASA, aspirin) have strong position
      confirmed by many multicenter clinical trials. They significantly reduce
      cardiovascular risk and increase life expectancy. Latest recommendations on
      management of hyperlipidemias in children expand indications for screening of
      lipid level imbalances and indicate statins as main pharmacotherapy after failure
      of life style changes. On the other hand acetylsalicylic acid is not used so
      broadly. Only children at high risk of thrombosis may benefit from its
      antiplatelet property. This review presents the latest recommendations and the
      therapeutic role of these medications in pediatric population.

PMID- 23879006
TI  - [Halitosis--diagnosis and treatment].
AB  - Halitosis (bad breath) applies to according to various authors--even 25-50% of
      the population. Volatile sulfur compounds are frequently encountered in the
      exhaled air. The article presents the most common causes of halitosis. It is
      believed that approximately 80-90% of the causes of halitosis are located in the
      head area (mouth, ear, nose, throat), whereas the remaining cases correspond to
      systemic illness, such as of the stomach and lung, certain medications or food.
      This paper describes different means to assess halitosis, which can be helpful in
      determining the diagnosis. The article describes ways to treat the symptoms and
      causes of halitosis associated with oral cavity. In patients who have had another
      source of halitosis, additional diagnostic procedures and appropriate treatment
      must be performed. Given the prevalence of the problem of the malodour and its
      impact on the quality of everyday life, halitosis is a phenomenon that should not
      be underestimated. The causes need to be detected and an appropriate therapy must
      be performed. Patients with diagnosed halitophobia should be directed to
      appropriate specialists.

PMID- 23879007
TI  - [Hypoaldosteronism].
AB  - Hypoaldosteronism is a clinical condition characterized by a deficiency of
      aldosterone or its impaired action at the tissue level. The disorder may result
      from disturbances in renal renin production and secretion, conversion of
      angiotensin I to angiotensin II, adrenal aldosterone synthesis and secretion, or
      from abnormal responsiveness of the target tissues to aldosterone.
      Hypoaldosteronism has a wide spectrum of clinical manifestations, ranging from
      asymptomatic hyperkalemia to life-threatening depletion of fluid volumes.
      Although the disease, if unrecognized and untreated, seems to be associated with
      increased morbidity and mortality compared to the normal population, it was
      surprisingly rarely reviewed in the literature. The aim of this paper is to
      summarize the present state of knowledge on the etiology, clinical presentation,
      diagnosis and treatment of various forms of hypoaldosteronism.

PMID- 23879008
TI  - [Endocrine abnormalities in HIV-infected patients].
AB  - HIV infection is associated with a number of adverse consequences, including
      endocrine disorders. The endocrine changes associated with HIV infection have
      been studied in depth and, as the results of so far carried out studies suggest,
      their aetiology is usually multifactoral. Their pathogenesis includes direct
      infection of endocrine glands by HIV or opportunistic organisms, infiltration by
      neoplasms and adverse effects of drugs. Endocrine problems that most frequently
      affect this group of patients include: hypogonadism, adrenal insufficiency,
      thyroid disorders, impaired growth hormone release, lipodystrophy and bone loss.
      They may develop in both the early as well as late stages of the infection,
      ranging from subclinical disturbances to overt endocrine symptoms. The purpose of
      this paper is to review the aetiology, clinical manifestations, diagnosis and
      treatment of HIV-associated endocrine disturbances with a special emphasis on the
      most recent literature.

PMID- 23879009
TI  - [Metformin--new treatment strategies for gynecologic neoplasms].
AB  - Metformin, a drug from the biguanide class, is now one of the most widely used
      drugs in the treatment of type 2 diabetes. This drug was also used in the
      treatment of polycystic ovarian syndrome and recent reports indicate the
      possibility of using this drug in oncology. Latest findings show that metformin
      has an anticancer effect. Influencing the transduction mechanisms primarily
      through activation of protein kinase activated by 5'AMP (AMPK) regulates the
      activity of the AMPK/mTOR signaling pathway. MTOR pathway dysregulation may be a
      factor in the pathogenesis of various human diseases, especially cancers.
      Overactivation of mTOR is observed in malignant cells and is associated with
      their resistance to treatment. It can therefore be concluded that metformin as an
      inhibitor of mTOR may be a factor that suppresses tumor development. There are
      also studies showing that metformin prevents the formation of metastases,
      reducing tumor vasculature and improves the effectiveness of anticancer drugs.
      The anticancer effect of metformin has been proven in the treatment of colorectal
      and breast cancer. The current studies reports the positive effects in the
      treatment of gynecological cancers such as ovarian, endometrial and cervical
      cancer. Incidence for these tumors in 2009 in Poland was: for ovarian cancer
      11.01100000; for endometrial cancer 15.0/100000; for cervical cancer 10.5/100000.
      Metformin has antitumor activity in monotherapy and also synergistically with
      other anticancer agents. Metformin has antiproliferative properties; reduces the
      VEGF levels, causing a reduction in tumor vasculature; causes an increase in
      progesterone receptor, which increases the response to hormonal therapy; inhibits
      the expression of glyoxalase I, mediating resistance to chemotherapy; decreases
      in the concentration of human telomerase; reduces the activity of Akt and Erk
      kinases, key regulators of metabolism and progression of tumors and also inhibits
      the formation of metastases.

PMID- 23879010
TI  - [The biological function of L-carnitine and its content in the particular food
      examples].
AB  - The aim of this article is to provide information about L-carnitine, its
      physiological role in the human body and its content in some foods. This chemical
      compound is mainly synthesized in the liver, kidney and brain and is composed of
      two aminoacids, lyzine and metionine. L-carnitine regulates the level of acylo
      CoA and CoA in the mitochondium and cytozolum, and it provides acetyl moieties
      for the biosythesis of acetocholine. L-carnitine plays a vital function in the
      metabolism of lipids and it carries long-chain fatty acids into mitochondria for
      beta-oxidation. An increase of the amount of L-carnitine in the human body may
      lead to reduction and inhibition of production of fatty tissue. Despite the fact
      that human body can synthesise L-carnitine, about 80% of this chemical compound
      is delivered by food. It is crucial, especially for people who are on a slimming
      diet, to choose products rich in L-carnitine because this compound may
      potentially reduce the body weight. Animal by-products contain the highest amount
      of L-carnitine, and these are, e.g , kangaroo meat (637 mg), horse meat (423mg),
      beef (139 mg per 100 g of dry weight). The amount of L-carnitine in milk products
      may range from 1,4 to 42,8 mg per 100 g of dry matter. Vegetables and fruits are
      products which contain less than 5 mg of L-carnitine per 100 g of dry matter.
      Lipids are also very low in L-carnitine, e.g sunflower oil is free from this
      compound. It is worth mentioning that mushrooms are richer in L-carnitine than
      plants. The amount of L-carnitine (53 mg/100 g dry matter) in pleureotus
      ostreatus equals approximately 100 g of minced pork.

PMID- 23879011
TI  - History of Polish Society of Forensic Medicine and Criminology, 1938-2013.

PMID- 23879012
TI  - [Validity of post-mortem computed tomography angiography (PMCTA) in medico-legal
      diagnostic management of stab and incised wounds].
AB  - The report presents an analysis of results of multi-phase post-mortem computed
      tomography angiography (MPMCTA) scans performed at the Chair of Forensic
      Medicine, Jagiellonian University Medical College, in cases of stab wounds and
      incised wounds, as confronted with the results of conventional medico-legal
      autopsies. The analysis of the material points to a validity of PMCTA scans as
      supplementing post-mortem medico-legal examinations and being capable of
      providing significant data that affect final conclusions and adding new quality
      to recording post-mortem observations.

PMID- 23879013
TI  - Sudden death due to malignant hyperthermia during general anesthesia.
AB  - The authors present a case of malignant hyperthermia. The article discusses the
      death of a 4-year old boy who appeared to be perfectly healthy and underwent
      dental treatment under general anesthesia. The procedure went well at the
      beginning, but suddenly complications developed, such as cardiac rhythm disorders
      and increased body temperature, subsequently, muscle rigidity appeared. Such
      symptoms are characteristic for an inherited disease called malignant
      hyperthermia. Despite professionally performed resuscitation and help of an
      emergency unit, the patient died.

PMID- 23879014
TI  - [An unusual case of suicidal carbon monoxide poisoning committed using a portable
      barbecue grill].
AB  - Fatal carbon monoxide poisoning is relatively often encountered in medico-legal
      practice. Although we usually deal with events of an accidental nature, cases of
      suicidal character are also quite common, both in Poland and in other European
      countries. The source of a poisonous gas that is used by a suicide to take his
      life are usually exhaust fumes from cars and home gas water-heaters that are
      released in closed spaces. In the present report, the authors present an atypical
      case--the only such instance in the history of the Krakow Department--where a
      high carbon monoxide concentration level was achieved by burning briquetted coal
      in a typical portable barbecue grill. A 65-year old male lit the grill in a room
      locked from inside, where he had previously sealed all cracks and vents; he left
      a written message by the entrance where he warned his flatmates about the
      presence of gas. The investigation determined that the predominant underlying
      reason of his committing suicide were health problems. As it follows from the
      analysis of literature on the subject, despite extensively available materials,
      such a suicide method is exceptionally rare in the European or American culture,
      where isolated cases only are presented. On the other hand, the authors emphasize
      the fact that within the last score of years, using barbecue grills in suicidal
      poisoning has become exceedingly common in the Far East countries. The present
      report points to certain historical and cultural determinants that may affect
      such a distinct geographical polarization of the discussed method being used in
      some Asian countries and refers to a widely discussed by specialists significant
      role of mass media in popularization of such a suicide method.

PMID- 23879015
TI  - [Top-hat keratoplasty in surgical treatment of bullous keratopathy].
AB  - Outcomes of different modifications of top-hat keratoplasty were assessed in 48
      patients (48 eyes) with bullous keratopathy. In the 1st group manual top-hat
      keratoplasty was performed in 7 patients. 30 patients of the 2nd group underwent
      manual half-top-hat keratoplasty. In the 3rd group femtosecond laser-assisted top
      hat keratoplasty was performed in 11 patients. All keratoplasty techniques used
      in the study provide high rate of clear graft retention. Manual half-top-hat
      keratoplasty is technically easier compared to manual top-hat keratoplasty though
      having similar outcomes and does not require the use of any additional equipment.
      Femtosecond laser-assisted top-hat keratoplasty allows to achieve superior
      optical results, trephination is performed promptly and with minimal tissue
      trauma. This new keratoplasty technique is a promising procedure and requires
      further detailed investigations.

PMID- 23879016
TI  - [Some features of phakoemulsification in lens subluxation].
AB  - A study was performed to compare three techniques of phakoemulsification (PE)
      (use of iris retractors, capsular ring and their combination) in 315 patients
      (407 eyes) with cataract and lens subluxation of different degree. A PE technique
      was proposed and studied in clinic using developed method of extracapsular
      fragmentation of two nuclear halves. Proposed and clinically approved surgical
      techniques (10 years follow-up) as well as differentiated approach for choosing
      surgical method in patients with lens subluxation let perform surgery less
      traumatically with minimal complication rate, get excellent and stable results
      during long-term follow-up.

PMID- 23879017
TI  - [Estimation of age-related features of acoustic density and biometric relations
      of lens based on combined ultrasound scanning].
AB  - Results of combined ultrasound scanning for estimation of acoustic lens density
      and biometric relations of lens and other eye structures are presented. A group
      of 124 patients (189 eyes) was studied; they were subdivided depending on age and
      length of anteroposterior axis of the eye. Examination algorithm was developed
      that allows selective estimation of acoustic density of different lens zones and
      biometric measurements including volumetric. Age-related increase of acoustic
      density of different lens zones was revealed that indirectly shows method
      efficiency. Biometric studies showed almost concurring volumetric lens
      measurements in "normal" and "short" eyes in spite of significantly thicker
      central zone of the latter. Significantly lower correlation between anterior
      chamber volume and width of its angle was revealed in "short" eyes and "normal"
      and "long" eyes (correlation coefficients 0.37, 0.68 and 0.63 respectively).

PMID- 23879018
TI  - [Clinical course and results of treatment of zone I retinopathy of prematurity].
AB  - 23 infants (46 eyes) with zone I retinopathy of prematurity (ROP) were examined.
      Zone I ROP is characterized with distinctive clinical presentation, course,
      prognosis and treatment results. Coagulation of retina in active I zone ROP
      showed efficacy in 70%: in posterior ROP - 56,3%, in anterior ROP - 79%. Surgery
      was performed in 12 eyes with stage 4a-5 ROP. Lens-sparing vitrectomy at
      gestational age of 44-45 weeks resulted in partial or total reattachment of
      retina that was achieved in 5 eyes with 4a-4b stage ROP. In the other cases the
      surgery played an eye preserving role. Late functional results are indicative of
      multifactorial pathogenesis of visual function impairment in infants with I zone
      ROP.

PMID- 23879019
TI  - [Silicone oil tamponade as a risk factor of complications].
AB  - Morphological study was performed in enucleated eyes with chronic uveitis and
      phthisis bulbi in patients after vitrectomy with silicone oil tamponade. Silicone
      oil as a foreign substance was showed to aggravate chronic inflammation that
      results in intraocular sclerotic processes.

PMID- 23879020
TI  - [Spectral domain optical coherence tomography for evaluation of transpupillary
      thermotherapy efficacy in early uveal melanoma].
AB  - Prognostic significant signs of early uveal melanoma were revealed in 51 patients
      before and 3 months after a single transpupillary thermotherapy session using
      spectral domain optical coherence tomography with enhanced depth imaging, that
      allows planning of appropriate eye-preserving treatment.

PMID- 23879021
TI  - [Intraocular electrochemical lysis at the stage of endoresection of uveal
      melanoma (clinical experimental study)].
AB  - Introduction of novel techniques of tumor destruction allows endoresection to be
      a perspective eye-preserving method of uveal melanoma treatment. Further
      investigations are essential to assess endoresection efficacy.

PMID- 23879022
TI  - [Changes of retinal neurons and Muller glial cells in patients with type II
      diabetes in treatment of diabetic retinopathy with angiotensin-converting enzyme
      inhibitor].
AB  - Flicker-ERG (FERG) amplitude and glial indices Cg were measured to estimate
      angiotensin- converting enzyme (ACE) inhibitor Perindopril effect on retinal
      glial-neuronal interactions in patients with type II diabetes and diabetic
      retinopathy (DR). Intake of 5 mg Perindopril daily during 2 months improved
      photoreceptor and bipolar cells function in all stages of DR with the most
      significant effect in preproliferative DR (PPDR). After treatment course
      initially supernormal FERG scotopic glial indices reduced by 8,3-12 Hz (25-33%)
      in nonproliferative DR and PPDR and by 10% in proliferative DR. In photopic
      conditions moderate decrease of index was revealed in FERG by 30Hz only in PPDR.
      Obtained results show Perindopril to cause significant improvement of retinal
      glial-neuronal interactions in dark adaptation and poor positive dynamics in
      photopic conditions.

PMID- 23879023
TI  - [A novel model of artificial iris-lens diaphragm for reconstruction of extensive
      iris defects (experimental rationale)].
AB  - Experimental rationale is presented for novel model of artificial iris-lens
      diaphragm (ILD) that provides a better adaptation of diaphragm to anterior
      segment structures variable in size and reduction of pressure on ciliary body due
      to modifications in design of supporting elements. Presented model is good in
      self-centration, allows sutureless fixation in lens capsule or the other
      supporting structures in aniridia.

PMID- 23879024
TI  - [Pathogenic features and treatment options of different diabetic retinopathy
      stages].
AB  - An operative classification and up-to-date options of diabetic retinopathy
      management are presented in the article.

PMID- 23879025
TI  - [Incidence, structure and features of eye diseases in steelworkers].
AB  - Incidence and structure of eye diseases was studied in workers of Novokouznetsk
      Steelworks who have occupational hazards. High incidence of inflammatory and
      dystrophic diseases of eyelids and conjunctiva as well as cataract was revealed
      in steelworkers. The incidence of eye diseases was showed to rise with the
      increase of work period in hazardous environment.

PMID- 23879026
TI  - [Silent sinus syndrome (clinical case). New potential for enophthalmos
      correction].
AB  - Silent sinus syndrome (SSS) is a rare condition presenting with spontaneous
      enophthalmos and hypoglobus caused by volume reduction of maxillary sinus due to
      centripetal collapse of its walls. A case of SSS manifested during pregnancy in
      43 years old patient is presented. In 16 months after manifestation of symptoms
      endoscopic sinus surgery was performed with no postoperative improvement of
      ocular symptoms. Intraorbital injection of stabilized hyaluronic acid gel was
      performed for correction of globe position. In control ultrasound examination
      color Doppler mapping revealed improvement of regional blood flow on the side of
      injection.

PMID- 23879027
TI  - [Efficacy of physiotherapy and hygienic procedures in treatment of adults and
      children with chronic blepharitis and dry eye syndrome].
AB  - 110 patients aged from 3 to 42 years old were examined to estimate the efficacy
      of chronic blepharitis treatment: 50 patients with chronic blepharitis and dry
      eye syndrome (DES), 28 with DES due to computer vision syndrome and 32 with
      isolated chronic blepharitis. All patients received eyelid massage. If the
      secretion was too thick and difficult to evacuate from meibomian glands then duct
      probing was performed. In addition a complex of hygienic procedures was performed
      using phytoproducts ("Geltec-Medika", Russia): blepharoshampoo, blepharolotion,
      blepharogel 1 and 2. Moist warm pads (with blepharolotion and calendula
      extraction) were applied on the eyelids in 25 patients. Massage and probing of
      meibomian gland ducts and hygienic procedures were showed to be effective in
      management of clinical signs of chronic blepharitis including coexisting DES.
      Moist warm pads improve efficacy of background therapy in patients with meibomian
      gland hypofunction and have no effect in blepharitis with excessive meibomian
      gland secretion. Eyelid hygiene was showed to be effective in adults and children
      as well including infants.

PMID- 23879028
TI  - [Changes of intraocular cytokine level in patients with vascular and neovascular
      retinal pathology depending on pathologic process activity].
AB  - Cytokine and growth factors levels were estimated in anterior chamber humor of
      patients with different diseases manifesting with vascular and neovascular
      retinal changes and various pathologic process activity. 40 patients with macula
      edema, retinal and choroid neovascularization were examined. Process activity was
      determined based on data obtained using high-resolution optical coherence
      tomography and fluorescent angiography. Quantitative concentration of
      interleukine 6, 8, vascular endothelium growth factor and monocyte
      chemoattractive protein-1 in anterior chamber aqueous humor was measured using
      enzyme immunoassay. Increased level of cytokines studied was found in all forms
      of the diseases.

PMID- 23879029
TI  - [Functional tear production indices in thyroid eye disease].
AB  - Analysis of functional tear production indices in patients with Grave's disease
      and thyroid eye disease confirmed lacrimal gland involvement in inflammatory
      autoimmune process. Close direct correlation was found between tear production
      and main disease characteristics - severity and activity.

PMID- 23879030
TI  - [Proliferative potential of human corneal endothelium].
AB  - Despite of common opinion that mitotic processes in adult human corneal
      endothelium are absent the accumulated data show potential of these cells for
      proliferation. Mechanisms inhibiting endothelial corneal cells mitosis are
      illustrated. The data on possible ways of proliferation activation and cell
      division in vitro and in vivo is provided. A brief review of cell technologies
      applied in contemporary ophthalmology is given including method of personalized
      cell therapy, a way of effective medical impact on damaged corneal endothelium in
      early postoperative bullous keratopathy.

PMID- 23879031
TI  - [On some pathogenic features of diabetic retinopathy in type II diabetes mellitus
      and the role of antioxidants and ginkgo biloba].
AB  - Diabetic retinopathy is a microvascular complication of diabetes and has complex
      and multifactorial pathogenesis. Cascade of biochemical changes characteristic to
      other diabetes vascular complications leads to structural changes of retinal
      capillaries some of which are unique. As a result of all processes at different
      pathogenesis levels there is an increase of free radicals concentration and
      decrease of antioxidant protection thus provoking an oxidative stress in retina
      and endothelial dysfunction with subsequent hypoxia and activation of growth
      factors and promotion of neovascularization leading to loss of vision in patients
      with type II diabetes mellitus. Consideration of oxidative stress reduction and
      restoration of retinal antioxidant system using exogenous antioxidants is a
      promising issue for further research.

PMID- 23879032
TI  - [Experimental models of human retinal degenerations: induced models].
AB  - Existing approaches in experimental animal modeling of human retinal
      degenerations are reviewed, in particular models, in which pathological processes
      in animals were induced by chemical, biological and physical exposure.

PMID- 23879033
TI  - [Current methods of anti-angiogenic influence on newly formed corneal vessels].
AB  - Russian and foreign literature data on current methods of anti-angiogenic
      influence on newly formed corneal vessels in experiment and clinic was analyzed.
      Their advantages and negative effects are highlighted and the information about
      their combined use is provided. The conclusion about the need of further studies
      is made.

PMID- 23879034
TI  - [Radiodiagnosis in the planning of surgical treatment for extensive jaw cysts].
AB  - OBJECTIVE: To make an algorithm for the optimal planning of a surgical procedure
      in patients with jaw cysts. MATERIAL AND METHODS: Sixty-six patients were
      operated on using cystotomy. The planning stage used radiation examination,
      including 7 survey radiographies, 62 orthopantomographies, and 33 computed
      tomographies (CT). The informative indicators of the most commonly used radiation
      techniques for this abnormality were compared. High technology radiation
      techniques (CT) showed the highest informative and diagnostic values. CONCLUSION:
      The investigation indicated the relationship of a surgical technique and the
      anatomic and topographic relations of a pathological process. The findings make
      it possible to prevent complications and recurrences during this treatment
      modality and to create favorable conditions for bone regeneration.

PMID- 23879035
TI  - [Bolus contrast-enhanced multislice spiral computed tomography of the chest: new
      possibilities in the diagnosis of lung diseases].
AB  - OBJECTIVE: To elaborate optimal programs for bolus contrast-enhanced multislice
      spiral computed tomography (MSCT) of the chest for different types of tomographic
      scanners and in some lung diseases. MATERIAL AND METHODS: Contrast-enhanced MSCT
      findings were analyzed in 637 patients, 536 of whom presented with a focal
      pathological process in the lung and 101 had pulmonary emphysema. RESULTS: There
      is evidence proving the expedience of using the contrast medium iopromide that
      has an optimal balance between the high concentration of iodine and its excellent
      tolerance due to low osmolarity and low viscosity. CONCLUSION: Intravenous bolus
      contrast-enhancement using an automated injector can visualize chest organs in
      different phases of contrast enhancement, by significantly improving the quality
      of diagnosis and achieving 100% disease diagnosis comparable with its
      morphological diagnosis.

PMID- 23879036
TI  - [Efficiency of endobronchial ultrasonography in the diagnosis of peripheral lung
      masses].
AB  - OBJECTIVE: To evaluate the efficiency of endobronchial ultrasonography (EBUS) in
      the diagnosis of peripheral lung masses. MATERIAL AND METHODS: The investigation
      enrolled 38 patients, including 34 males; their mean age was 63.8+/-15.8 years.
      Bronchoscopy was carried out under local anesthesia in all the patients in their
      sitting position, by using a flexible endoscope, along with transbronchial lung
      biopsy (TBLB). During the study, a 20 mHz radial scanning ultrasonic miniprobe
      was successively introduced into the working channel of a bronchoscope through
      the ostium into the preselected bronchi. If the peripheral mass could be located
      by EBUS, after withdrawing the probe, TBLB was performed using biopsy forceps.
      RESULTS: EBUS could locate a pathological mass and perform TBLB in 34 (89.5%) of
      the 38 cases. The cumulative efficiency of TBLB was seen in 63.2% (24/38)
      patients: there was adenocarcinoma in 16 (42.1%) cases, squamous cell carcinoma
      in 6 (15.8%), hamarthoma in 1 (2.6%), and tuberculoma in 1 (2.6%). The predictors
      of biopsy efficiency were tumor sizes above 20 mm; bronchial drainage as shown by
      computed tomography; the central position of a miniprobe about the mass, the
      proximal position of a mass about the bronchial ostium; a less than one-and-a
      half-minute study; smoking index. CONCLUSION: Endobronchial ultrasonography is an
      effective and safe method for controlling endoscopic lung biopsy in peripheral
      lung masses.

PMID- 23879037
TI  - [Role of multislice spiral computed tomography in the evaluation of changes in
      upper airway volume during surgical treatment in patients with dentomaxillary
      abnormalities].
AB  - OBJECTIVE: To assess the role of multislice spiral computed tomography in the
      calculation of upper airway volume and its change in patients with different
      types of dentomaxillary abnormalities after orthognathic surgery. MATERIAL AND
      METHODS: Twenty-five patients with dentomaxillary abnormalities (19 and 6
      patients with Classes III and II dentomaxillary abnormalities, respectively) were
      examined. All the patients underwent two-jaw operations. Facial skeleton computed
      tomography was performed before treatment initiation and 6 months after surgery.
      The DICOM data were loaded in Dolphin Imaging 11.5 and a special program package
      was applied to calculate the volume of air space in the upper airway. The hard
      tissue and soft tissue points used to construct the planes setting the detection
      limits of air space in the upper airway were determined. RESULTS: After surgery,
      the patients with Class II dentomaxillary abnormalities display unilateral
      changes in our measured upper airway values (by increasing or reducing the air
      space); the majority of cases exhibiting higher values. Half of the patients with
      Class III had unilateral hanges, the increase or reduction in air space values
      varying in approximately equal proportions. CONCLUSION: Computed tomography
      permits the calculation of upper airway volumes before and after orthognathic
      treatment in patients with dentomaxillary abnormalities, which is in its turn of
      significant scientific and practical interest.

PMID- 23879038
TI  - [Use of dual-energy computed tomographic angiopulmonography in patients with
      chronic thromboembolic pulmonary hypertension before and after pulmonary artery
      thromboendarterectomy].
AB  - OBJECTIVE: To estimate the contribution of dual-energy computed tomographic (CT
      angiopulmonography t o a diagnostic algorithm in patients with chronic
      thromboembolic pulmonary hypertension (CTEPH) and its role in the evaluation of
      postoperative changes. MATERIAL AND METHODS: CT angiopulmonography was performed
      on the 64-slice Discovery HD 750 system (GE Healthcare) using the dual-energy
      scanning mode (140 and 80 kV). The examination results in patients with CTEPH
      were analyzed. RESULTS: All the patients were found to have typical CT signs of
      CTEPH: abnormal contrast enhancement of the pulmonary arteries, their dilatation
      and tortuosity; signs of right cardiac overload: right ventricular dilatation
      and/or hypertrophy, bronchial artery dilatation, decreased peripheral vascular
      pattern, mosaic pulmonary perfusion, and wedge-shaped perfusion defects on the
      iodine maps. Mosaic pulmonary perfusion areas were also found in all the
      patients. Perfusion defects were more clearly visualized when dual-energy CT by
      constructing iodine perfusion maps was used. Analyzing the perfusion maps in 6
      patients operated on revealed a 20-50% reduction in perfusion deficit.
      CONCLUSION: Information on the vascular bed and pulmonary perfusion may be
      obtained in patients with CTEPH within one investigation, which is important to
      plan surgical treatment. Construction of iodine pulmonary perfusion maps allows
      evaluation of perfusion recovery after artery thromboendarterectomy.

PMID- 23879039
TI  - [The first clinical experience with a new type of stents -scaffolds, under
      optical coherence tomography guidance].
AB  - OBJECTIVE: To analyze the first clinical experience with new types of stents,
      absorbable carcasses (scaffolds), under guidance of intravascular imaging
      techniques. MATERIAL AND METHODS: The paper gives the authors' experience in
      implanting eight Absorb BVS scaffolds in three patients during one operating
      session. All operations were performed under intravascular imaging guidance:
      three patients underwent 8 examinations of four vessels, by using optical
      coherence tomography (OCT) and 2 did using intravascular ultrasound study
      (IVUSS). RESULTS: The investigation demonstrated the possibility of implanting
      two devices partially applied to cover longer lesion lengths, the use of
      scaffolds after occlusion recanalization, and that of rather high pressure values
      to adapt a carcass if predilation was adequately performed. In one of the cases,
      control OCT could reveal timely the signs of extensive prolapse and early
      thrombosis, which had been unrecorded by angiography and IVUSS. To correct of the
      occurring problem, implantation of the second absorbable carcass into the first
      one was first successfully used by optimally adapting the girders and completely
      correcting the prolapse. CONCLUSION: The absorbable scaffolds may potentially
      signify a new stage in the development of interventional cardiology. However,
      their use requires the careful adherence of implantation specifications and
      primarily the accurate estimation of vessel sizes and accordingly a device that
      may be needed. The application of absorbable carcasses makes higher standards for
      the equipment and experience of interventional laboratories that plan their use.
      The possibility of using intravascular imaging is one the priorities in this
      series.

PMID- 23879040
TI  - [Individual approach to choosing the exposure time during myocardial perfusion
      single-photon emission computed tomography].
AB  - OBJECTIVE: To assess whether the quality of the results of myocardial perfusion
      single-photon emission computed tomography (SPECT) may be improved by applying an
      individual approach to choosing the exposure time of a study. MATERIAL AND
      METHODS: The results of myocardial perfusion SPECT with the radiotracer (RT)
      Technetril upon 25-sec (short) and 60-sec (long) exposures in 22 patients with
      valvular heart disease (VHD) and coronary heart disease (CHD) were
      retrospectively analyzed. The basis for the comparative assessment of the study
      results was the number of myocardial impulses (NMI). The reference informative
      value was taken as a NMI equal to 21,000-77,000. All the patients were divided
      into two groups: 1) those with a NMI of below 21,000 and 2) those with a NMI of
      above 21,000. The raw counts of RT and lesion extent were compared in each group
      during two exposure modes. RESULTS: No statistically significant differences were
      found between the raw counts of RT in the left ventricular segments upon short
      and long exposure regardless of NMI. Evaluation of lesion extent revealed
      differences in sizes and/or location in 14 (63,6%) patient upon various
      exposures, most (10 patients) of them were from Group I and only 4 patients were
      from Group 2, these patients having marked myocardial hypertrophy. CONCLUSION: To
      enhance the informative value of myocardial perfusion SPECT, it is expedient to
      individually choose exposure time for each patient, being oriented to the time
      taken to achieve a NMI of at least 21,000, which can be determined by making one
      planar scintigram in the left anterior oblique projection (LAO 45 degrees).

PMID- 23879041
TI  - [Potentialities of ultrasound study in the evaluation of developing chronic
      placental insufficiency].
AB  - The paper clarifies the ultrasound semiotics of the normal echographic pattern of
      the placenta in physiological pregnancy. It gives and systematizes the possible
      variants of the atypical placental structure in placental insufficiency in
      patients with spontaneous pregnancy and in women undergoing in vitro
      fertilization.

PMID- 23879042
TI  - [Experience in noninvasively quantifying hydrogen magnetic resonance imaging
      spectroscopic hepatic fat concentrations in patients with fatty hepatosis before
      and after treatment with Eslidin].
AB  - OBJECTIVE: To define the role of liver magnetic resonance (MR) spectroscopy in
      the evaluation of therapy for fatty hepatosis. MATERIAL AND METHODS: Spectra were
      studied in 49 patients (30 men and 19 women) whose mean age was 54+/-11 years. A
      study group consisted: 1) healthy volunteers (n = 10) and 2) patients with fatty
      hepatosis (n = 39) identified by clinical data. The patient group had two points:
      before and 6 months after treatment with Eslidin (based on polyunsaturated fatty
      acids). The lipid-to-water content ratio in the liver parenchyma was calculated
      for each patient. If its value was over 6.5%, the diagnosis of fatty hepatosis
      was considered verified. RESULTS: The findings showed that the ratio was not more
      than 3.2% in the group of healthy volunteers, which completely excluded hepatic
      fatty infiltration. In the patient group, the ratio was 15, 10, and 8.5% in 15,
      20, and 4 cases, respectively. Reexamination revealed a reduction in fat
      concentrations to normal values (56,4%) in 22 patients and a more than twice
      (31%) decrease in 12 patients. No reduction in fat content was found in 5 (12,8%)
      patients. CONCLUSION: Proton MR spectroscopy is a reproducible procedure that may
      be used to evaluate the efficiency of treatment for fatty hepatosis. H1
      spectroscopy can be used to evaluate the efficacy of some drugs for the treatment
      of this pathology.

PMID- 23879043
TI  - [The morphology, rate, and risk factors of restenosis during different
      endovascular treatment options].

PMID- 23879044
TI  - [Radiodiagnostic methods in the assessment of human body composition].

PMID- 23879045
TI  - [Rokitansky's theory of humoral pathology, virchow's theory of cellular
      pathology, and new phylogenetic theory of diseases. Etiology and pathogenesis of
      "metabolic pandemics"].
AB  - Virchow's theory of cellular pathology contains indirect indications that a)
      there are in vivo structural and functional units between the cell and the organ
      and b) common mechanisms operate in health and disease. It is proposed to use the
      phylogenetic theory to obtain an insight into the unified pathogenetic mechanism
      of atherosclerosis, diabetes mellitus, metabolic syndrome. and obesity. It
      includes 1) consideration of in vivo physiological and pathological processes in
      the context of biological functions and reactions, 2) phylogenesis of metabolic
      regulation at three levels: a) cellular (autocrine), b) paracrine cell
      communities (structural and functional units of each organ), c) organismic.
      Biological functions are trophologic, homeostatic, endoecological ("cleanliness"
      of intercellular medium), adaptive, locomotor reproductive and cognitive. 3)
      consideration of the successive three-step development of biological functions
      and reactions of pathological process in phylogenesis. Technical tools in
      phylogenesis include a) continuity, of formation of biological functions and
      reactions, b) biological subordination (later formed humoral mediators can not
      reverse effect of the phylogenetically earlier ones). Inconsistency of humoral
      regulation at different phylogenetic levels (autocrine, paracrine, organismic)
      constitutes the basis for common pathogenesis of all metabolic pandemics
      inclutding essential AH and insulin resistance.

PMID- 23879046
TI  - [Coronary calcinosis. State-of-the-art].
AB  - Atherosclerosis and coronary heart disease are the main causes of disablement and
      mortality in most developed countries. Clinical studies showed the relationship
      between coronary calcinosis and atherosclerotic lesions, the calcinosis area
      accounting for roughly 1/5 of the atherosclerotic plaque area. Calcinosis is
      quantitatively characterized by the calcium score determined by multispiral and
      electron-beam computed tomography. High calcium score suggests an increased risk
      of cardiovascular complications. Their treatment awaits further assessment since
      a number of studies revealed differential effect of various medicines on coronary
      calcification.

PMID- 23879047
TI  - [The influence of amlodipine on transcapillary metabolism of oxygen during
      coronary heart disease with insulin resistance].
AB  - This three-week open uncontrolled study included 34 men (mean age 53.14+-1.19 yr)
      with coronary heart disease (CHD) and insulin resistance (HOMA >2. 77); it was
      designed to estimate effect of amlodipine on transcapillary oxygen metabolism
      (TCOM). Multivascular stenosing coronary atherosclerosis was managed by
      aortocoronary bypass surgery. Traditional methods applied in specialized
      cardiological clinics were supplemented by TCOM measurement using a PA-2
      polarograph (Czech Rep.). Polarography revealed deterioration of TCOM parameters
      including permeability of hemocapillaries, adaptive reserves of the
      microcirculatory bed, and oxygen supply to the tissues. Amlodipine therapy
      demonstrated high antianginal potency of this drug and its ability to improve
      TCOM

PMID- 23879048
TI  - [S24-hour arterial pressure monitoring in patients with chronic cardiac failure
      and the state of renal function].
AB  - The 24-hr AP profiles were obtained in 194 patients with chronic cardiac failure
      (CCF) depending on the glomerular filtration rate (GFR). It was shown that 24
      hour arterial pressure monitoring markedly improves detection of potentially
      dangerous changes of AP The target AP was achieved in 42.9 and 18.4% of the
      patients with GFR < or = 45.1 and > or = 69.8 ml/min/1.73 m2 respectively.
      Episodes of systolic arterial hypotony were diagnosed in 51.0 and 26.5% of the
      patients with GFR < or = 45.1 and 69.8 ml/min/1.73 m' respectively; episodes of
      diastolic arterial hypotony in 71.4 and 61.2% of the patients with GFR < or =
      45.1 and > or = 69.8 ml/min/1.73 m2 respectively. Duration of systolic and
      diastolic arterial hypotony during 24 hr correlated with the level of glycemia
      and the age of the patients respectively.

PMID- 23879049
TI  - [The incidence and significance of chronic obstructive pulmonary disease in
      patients with myocardial infarction and elevated st segment].
AB  - The aim of this work was to study the clinical picture and outcome of myocardial
      infarction in patients w'ith elevated STsegment and concomitant COPD. It involved
      529 patients. Group I included 65 (12.3%) patients with previously diagnosed
      COPD. Group 2 was comprised of 464 (87.7%) patients without COPD. The study
      lasted 1 year. The patients of group 1 were older and smoked more heavily than in
      group 2. They had a higher clinical class of cardiac failure and more frequently
      showed reduced (by 40%) left ventricular ejection friction. Also, they required
      significantly longer hospital treatment, developed more complications, and showed
      higher inpatient mortality rate. The annual prognosis for them was less
      favourable than in group 2.

PMID- 23879050
TI  - [The predictors of progression of myocardial dysfunction in patients with
      essential hypertension and heart valve calcification].
AB  - The article presents the results of a study to identify predictors of progression
      of myocardial dysfunction in patients with essential hypertension (EH) and
      calcification of the heart valves (CCS) using regression analysis, with this
      purpose examnined 245 patients. In patients with essential hypertension and HVC
      as the most informative predictors of progression of myocardial dysfunction were
      presents of combined valvular damage, severity of aortic stenosis and its
      progression in dynamics.

PMID- 23879051
TI  - [The total content and oligomeric transformations of surfactant protein d in
      bronchoalveolar lavage fluid in bronchial asthma and gastroesophageal reflux
      disease: the role in deterioration of the immune response].
AB  - The study of pathogenesis of bronchial asthma (BA) and gastroesophageal reflux
      disease (GERD) or their combination showed that the intensity of inflammation and
      the choice between Thl and Th2 immune responses are determined by macrophages
      (elements of congenital immunity). Lung surfactant protein D (SP-D) existing in
      various oligomneric forms (as monomer trimer, dodecamer, multimer) plays an
      important role in the mechanism of transformation ofalveolar macrophage
      phenotype. Patients with BA+GERD have higher SP-D level in the bronchoalveolar
      lavage fluid than those with GERD alone but lower than patients with BA. SP-D
      dodecamers were found only in BA patients given basaLtherapy with inhaled
      glucocorticoids (IGC). It suggests that the presence of dodecamers in the lavage
      fluid may result firom anti-inflammatory action of IGC. They are absent in
      patients with BA+GERD treated with IGC probably because GERD enhances
      inflammatoly changes in the lungs of BA patients despite basal therapy These data
      together with results of experimental acidification of lavage fluid from BA
      patients give reason to hypothesize that microaspiration of acidic gastric
      contents frequently associated with GERD is a cause of local decrease of pH in
      different segments of the bronchial tree triggering two pathogenetic mechanisms:
      (I) programming proinflammatory MI phenotype of alveolar macrophages, increased
      production of nitric oxide, nitrosation of SP-D and destruction of its anti
      inflammatory multimers ; (b) direct destruction ofSP-D oligomers in the acid
      medium. Both mechanisms reduce the level of anti-inflammatory SP-D multimers and
      increase the level ofproinflammatory monomers. Thus, decreased pH in lower
      airways is a real pathogenetic factor of anti-inflammatory shift in the
      oligomeric SP-D composition accounting for the inflammatory reaction of lungs in
      GERD.

PMID- 23879052
TI  - [Systemic manifestations of primary sclerosing cholangitis].
AB  - Primary sclerosing cholangitis (PSC) is a chronic slowly developing cholestatic
      diseases of liver characterized by non-purulent destructive inflammation and
      fibrosis of bile ducts leading to secondary biliary cirrhosis. PSC etiology
      remains unknown and the disease is regarded as an autoimmune pathology. In 60-80%
      of the patients PSC combines with other autoimmune diseases (over 40 nosological
      forms). This paper deals with the diversity and prevalence of systemic
      manifestations of PSC in a group of 93 patients admitted to Tareev Nephrology
      Clinic. Autoimmune diseases were diagnosed in 79.6% of the patients. PSC was most
      frequently associated with ulcerative colitis (49.5%), Crohn's disease (17.2%),
      hemorrhagic vasculitis (8.6%) and autoimmune thyroiditis (7.59%). Nervous system,
      kidneys, lungs and eyes were affected less frequently. 20.3% of the patients had
      more than one (2-5) manifestations of PSC in different combinations. It is
      concluded that the knowledge of extrahepatic PSC symptoms will promote its early
      diagnosis in patients with cholestasis of uncertain origin.

PMID- 23879053
TI  - [Comparative estimation of diagnostic tests for helicobacter pylori and the
      spectrum of gastric mucosal microflora in gastritis and ulcer disease].
AB  - We estimated specificity and sensitivity of diagnostic tests for H. pylori (HP)
      infection in patients with gastroduodenal problems and studied species
      composition of gastric mucosal microflora in gastritis and ulcer disease. The
      following characteristics have been determined as the most informative signs of
      HP infection: HP fecal antigen, plasma total antibodies (IgG, IgA, IgM) against
      CagA, histological (cytological) findings confirming the presence of HP antigens
      in biopsies, rapid urease test, the presence of bent rods morphologically
      resembling HP in gastric mucosa biopsies cultured in the glycol medium for
      sterility control. The use of these signs (at least three) in combination ensures
      efficacious diagnostics of HP infection for the substantiation of its traditional
      therapy. The study of the spectrum and occurrence of gastric mucosal microflora
      revealed the predominance of Streptococcus, Staphylococcus, Candida fungi, and HP
      in patients with gastritis and Streptococcus, HP and Candida in those with ulcer
      disease at a mean concentration of microbial cells 3.41 and 2.71 CF/gg
      respectively. Significant differences were documented only in the occurrence of
      HP and Candida.

PMID- 23879054
TI  - [Postoperative control sanitation laparoscopy of omental SAC in the treatment of
      pancreonecrosis complicated by abdominal sepsis].
AB  - The study including 26 patients with pancreatonecrosis (PN) was aimed at
      estimating the efficiency ofprogrammed control sanitation laparoscopy (CSL) of
      the omental bursa in the postoperative period. The decrease ofpostoperative
      complications from 49,8% to 26.6% (p<0 ,05),fatal outcomes from 20,5% to 15,4%
      (p<0, 05) in comparison with 44 control patients who underwent traditional open
      sanitation of the omental bursa was documented It was proved by the method of
      cardiointervalography that laparoscopic sanitation decreases the severity of
      intraoperative lesions, prevents the overtension of the adaptative mechanism and
      suppression of reserve compensatory potential of the patients 'organism in
      comparison with open sanitative surgery

PMID- 23879055
TI  - [The state of oral cavity in patients with hepatitis A].
AB  - The aim of the study was to estimate oral cavity condition in 42 patients aged 25
      58 years with hepatitis A. Forty patients without hepatic pathology served as
      controls. Hepatitis A is known to be associated with inflammation of oral mucosa
      with stomatitis occurring in 78.5% of the patients, glossitis in 71.4%, cheilitis
      in 64.3%, marginal periodontal inflammation in 85.7%. Oral mucosal lesions
      confound the clinical picture of hepatitis. The prevalence of caries and its
      complications in patients with hepatitis A amounts to 95.2%. Results of our
      studies confirm the necessity of early stomatological examination of such
      patients.

PMID- 23879056
TI  - [Serum phospholipids in differential diagnostics of acute alcohol and salmonella
      gastroenteritis].
AB  - The aim of the study was to estimate the possibility of using the serum
      phospholipid spectrum for differential diagnostics of acute alcoholic and
      salmonella gastroenteritis. It included 50 patients and 50 healthy subjects. The
      following fractions were measured: total lipophospholipids (LPL), sphyngomyelin
      (SM), phosphatitylcholine, (PC) and phosphatidylethanolamine (PE). The serum
      phospholipid composition in patients of the two groups was significantly
      different. Salmonella gastroenteritis was characterized by reduced LPL and
      increased PC levels. Acute alcohol gastroenteritis was associated with elevated
      LPL, PE levels and reduced PC level. Relative LPL, PE levels in salmonella
      gastroenteritis were significantly higher and PC levels lower than in alcohol
      gastroenteritis. In the latter the LPL level was twice that in salmonella
      gastroenteritis whereas PC level was 1.5 times lower

PMID- 23879057
TI  - [Endothelial dysfunction in rheumatic patients].
AB  - Aim - to investigate the relationship between indicators of endothelium
      activation and markers of inflammatory activity, in rheumatic patients. The
      study, involved 112 patients including 34 with systemic lupus erythematosus (SLE)
      and 78 with rheunmatoid arthritis (RA) aged from 19 to 62 years. The markers of
      endothelium activation, indices of inflammatory activity and correlation between
      them were investigated Patients with RA and SLE exhibited disturbed endothelial
      fimction, increased level of soluble vascular cell adhesion molecule-1 (sVCAM-1)
      and von Wlllebrand factor antigen (Ag:vW), desquamated endotheliocytes (DE) in
      comparison with control (p<0, 1). Interleukin-8 (IL-8) levels in RA and SLE were
      significantly higher than in a control: 412,8 pg/ml, 331,1 pg/ml, 208 pg/ml
      respectively (p < 0,01). Significant positive correlation between RA and SLE
      activity scores (estimated from DAS28 and SLAM/SLEDAI respectively) and market's
      of endothelial dysfimction (sVCAM-I, Ag:vW DE) was documented Correlation co
      efficients were R = 0, 82, 0,80 and 0,85 respectively, p < 0, 01 for RA patients;
      R = 0,64, 0, 69 and 0, 61, p < 0, 01 for SLE patients (SLAM); Spirmnen s
      coefficients 0,64, 0,53 and 0,81, p < 0,01 Jbr SLE patients (SLEDAI). Levels of
      endothelial dysfunction markers in RA and SLE patients increased with increasing
      indices of inflammatomy activity. Increased levels oflL-8, sVCAM-1, Ag:vW DE in
      patients with RA and SLE lead to the damage of endothelium.

PMID- 23879058
TI  - [Lipoid necrobiosis in the practical work of a therapist and dermatologist].
AB  - This paper deals with the main aspects of etiology and pathogensis, clinical
      picture and therapy of lipoid necrobiosis. A case of successful treatment of the
      disease that developed long before clinical and laboratory manifestations of
      disturbed carbohydrate metabolism is reported.

PMID- 23879059
TI  - [Peculiarities of clinical picture and differential diagnostics of lupus
      erythematosus tumidus].
AB  - This review is devoted to differential diagnostics and treatment of lupus
      erythematosus tumidus, a rare form of lupus erythematosus, the data on which are
      practically absent in the Russian-language literature. The overview of foreign
      literature is supplemented by personal observations of the authors. Clinical
      cases are illustrated by photographs and the description of the
      pathomorphological picture of the disease. Special attention is given to its
      differential diagnostics bearing in mind the variety of its manifestations. This
      information is intended for therapists, rheumatologists, and dermatologists.

PMID- 23879060
TI  - [Myocardial infarction in colon cancer].
AB  - Paraneoplastic syndromes have a variety of clinical manifestations most
      frequently resembling systemic diseases and phlebothrombosis. Also,
      hypercoagulative paraneoplasic syndrome may have some clinical features of
      myocardial infarction which makes difficult nosological diagnostics.

PMID- 23879061
TI  - [The cultural, economic and social context of Ramazzini's Diatriba in the second
      half of the 17th century--in memory of Pericle Di Pietro on occasion of the third
      centenary of the publication of the final edition of the Diatriba (Padua, 1713)].
AB  - The paper aims at analyzing the development of Ramazzini's train of thought in
      Diatriba within the cultural, economic and social context of the Duchy of Modena
      in the second half of the seventeenth century. The period was characterized by a
      deep recession affecting every aspect of life in the territory: culture was
      mostly at the service of the court's image, the economy, mainly based on
      agriculture, was in crisis and many crafts depended on the demands of the
      nobility. The culture of the Este court had, however, little influence on
      Ramazzini's ideas, whereas social and economic aspects were the stimulus to his
      experimentalism via observation. In this context, Ramazzini was an illuminated
      nonconformist, who analysed the vulnerability of the population with an
      anthropological approach that embraced individuals, environment, social and
      economic status.

PMID- 23879062
TI  - [Mortality and morbidity among municipal waste workers in Rome: a cohort study].
AB  - INTRODUCTION: The adverse health effects associated with waste treatment
      processes are of great concern as large population groups and workers may be
      exposed to refuse-derived toxic substances. The main effects are respiratory and
      gastrointestinal infections, reduced lung function, irritations, allergic
      reactions, and injuries. OBJECTIVE: To evaluate morbidity and mortality among a
      cohort of municipal waste workers in Rome. METHODS: All 6839 workers (18.6%
      women) involved in waste collection, transportation and landfill disposal
      employed since 01/01/1994, with a minimum period of employment of five years were
      enrolled and with follow-up until 31/12/2009. The assessment of vital status was
      carried out through linkages with information systems (municipality records,
      mortality and hospital information systems), and through contacts with
      municipalities of residence. Gender specific standardized mortality (SMR) and
      hospitalization (SHR) ratios were calculated, using regional population mortality
      (and hospitalization) rates. RESULTS: Overall, in this cohort workers had the
      same mortality as the population of the Region. Hospitalizations for natural
      causes were significantly higher than expected among workers involved in
      transportation (SHR = 1.25, 95% CI = 1.13-1.38) and in waste collection (SHR(men)
      = 1.14, 95% CI = 1.07-1.22; SHR(women) = 1.65, 95% CI = 1.47-1.84). Among women
      there was an excess of hospitalizations for respiratory diseases (SHR = 1.95, 95%
      CI = 1.33-2.77), for digestive system disorders (SHR = 1.37, 95% CI = 1.03-1.79)
      and for injuries and intoxications (SHR = 2.28, 95% CI = 1.69-2. 99).
      CONCLUSIONS: The study did not find any increased mortality among the workers of
      either sexes. Female workers deserve further surveillance mainly due to an
      increased risk of trauma and respiratory and gastrointestinal disorders.

PMID- 23879063
TI  - Pleural mesothelioma: epidemiological and public health issues. Report from the
      Second Italian Consensus Conference on Pleural Mesothelioma.
AB  - Malignant mesothelioma is closely connected to asbestos exposure, with
      epidemiological patterns closely reshaping the geography and history of asbestos
      exposure. Mechanisms of causation and of interaction of asbestos fibres with
      pleura are complex and currently not yet completely understood. Curative efforts
      so far provided little results. Italy shows one of the highest incidence of MM
      and developed a network of specialized cancer registries in order to monitor
      disease occurrence and describe its epidemiology in details. The second Italian
      Consensus Conference on Pleural Mesothelioma convened in Torino on November 24th
      25th, 2011. Besides the main consensus report summarizing the contribution of the
      different expertises, that was published elsewhere, the participants in 'Public
      Health and Epidemiology' section decided to report in major details the evidence
      and the conclusions regarding epidemiology, causative mechanisms and the public
      health impact of the disease.

PMID- 23879064
TI  - [Ergonomics and productivity: an example applied to a manufacturing industry].
AB  - BACKGROUND: The survival of manufacturing in the western world also depends on
      the ability to increase productivity. To achieve this goal, it is necessary to
      recover the efficiency of all workers suffering from upper limb biomechanical
      overload disease. Ergonomic methods can be a valuable tool in solving this
      apparent conflict: operatives'productivity and health. METHODS: After carrying
      out an ergonomic education and training programme for all company employees and
      risk assessment for upper limb biomechanical overload through the OCRA checklist
      method, a programme of improvements on a production line was planned and tested,
      mainly based on international and European standards. RESULTS: Within
      approximately 2 years, thanks to changes in workplace layout and organization, a
      significant reduction of 22.7% in risk level was achieved and, at the same time,
      a 16% increase in productivity. DISCUSSION: An ergonomic approach based on
      global, interdisciplinary and participatory principles in the case considered
      showed that it is possible to match increased productivity with decreased risk.
      In this specific case application of ergonomic principles during product design
      was rather poor, which is typical of companies working for third party customers.

PMID- 23879065
TI  - [Measurement of real personal noise attenuation using earplugs with the E-A-Rfit
      system].
AB  - BACKGROUND: The assessment of efficiency of hearing protection devices (HPDs),
      conducted above statutory limits, must be made using a standardized method while
      devices are worn; however, standardized and suitable laboratory conditions are
      difficult to encounter at the workplace. To overcome this problem, there are
      methods of measurement at the workplace such as "field-microphone-in-real-ear" (F
      MIRE). OBJECTIVES: The study was concerned with the measurement of real noise
      attenuation using earplugs and a new evaluation system: we checked the difference
      between "real" attenuation (at workplace) and "theorical" attenuation (reproduced
      in the laboratory) as stated by the manufacturer. METHODS: We used the E-A-Rfit
      computerized method, which measures the loss of attenuation of earplugs in the
      ear, calculating the difference of sound pressure between an "outside" microphone
      and an "inside" one, in relation to the same earplug. The measurements at the
      workplace were carried out on eight subjects with good hearing levels (aged
      between 20 and 25 years), who were trained to wear the devices correctly. After
      the tests carried out with the E-A-Rfit system, which does not require a
      subjective answer, we obtained graphs and tables showing real noise attenuation.
      RESULTS/CONCLUSIONS: We propose a comparison between hearing threshold for
      frequency, personal attenuation rating (PAR) and single number rating (SNR,
      provided by manufacturer): a difference of 10 dB (PAR 27 db vs. SNR 37 dB) was
      clearly evident although dissimilar methods were used to obtain such values. The
      instrument is rapid, simple and objective to use and also allows personalized
      information and training for every worker.

PMID- 23879066
TI  - [Looking for "lost occupational cancers": a systematic evaluation of occupational
      exposure in a case series of cutaneous squamous cell carcinomas in Italy].
AB  - BACKGROUND: Cutaneous carcinomas are tumors with a potential occupational
      etiology due to exposure to established carcinogens such as polycyclic aromatic
      hydrocarbons (PAH), ionizing radiation, ultraviolet (UV) radiation and arsenic.
      The occupational origin of such neoplasms is hugely underestimated in Italy.
      OBJECTIVES: To asses the proportion of Squamous Cell Carcinomas (SCC) cases with
      a previous occupational exposure to carcinogens. METHODS: We systematically
      evaluated occupational exposure in a series of consecutive cases, discharged in
      the period 2010-11 from the Dermatology Unit of Varese Hospital, Italy, with a
      histological diagnosis of SCC. Through a structured telephone interview we
      identified patients with a potential exposure to skin carcinogens. As a second
      level step, an extensive evaluation by an occupational physician was performed to
      assess the occupational etiology in those selected cases. RESULTS: 105 patients
      were identified (65 men). 15 male cases out of a total of 85 patients who did the
      telephone interview, revealed a potential occupational exposure; 7 cases were
      confirmed as occupational cancers after second-level evaluation (proportion of
      male occupational cases = 13.2%). UV radiation and PAH were recognized as major
      causal agents. Applying those results to the national incidence data, we
      estimated a number of 700 annual occupational cases, 100-fold more than the cases
      currently evaluated by the Italian National Workers Compensation Authority.
      CONCLUSIONS: Our results revealed that occupational SCC is still at present a
      substantially "lost disease" in Italy. Greater attention and enhanced
      collaboration between specialists is thus needed to overcome this tendency.

PMID- 23879067
TI  - [Symptoms and upper limb work-related musculo-skeletal disorders among 173
      supermarket cashiers].
AB  - BACKGROUND: Cashiers in supermarket chains have long been considered at risk for
      the development of work related musculo-skeletal disorders of the upper limbs (UL
      WMSDs). The aim of this study was to assess the prevalence of UL-WMSDs among
      workers operating supermarket cash tills and, after clinical tests, their
      frequency. METHODS: A standardized questionnaire was given to a random group of
      173 workers in order to collect information regarding symptoms in the upper limbs
      (pain and parasthesia). Among the 111 workers who reached a "positive clinical
      history threshold" we selected a random sample of subjects to undergo clinical
      tests (professional medical care, ultrasound examination, electro-neurographic
      examination). RESULTS: 64% of the workers had a positive clinical history for UL
      WMSDs. The most frequently reported disorder was pain, especially in the
      shoulder, while 37% of workers suffered from one or more disorders of the upper
      limbs. Clinical tests were performed on 51 workers (47 women) whose average
      length of service was 20 years and 2/3 were part-time workers; a total of 43 UL
      WMSDs (59%) were diagnosed in 30 workers, including 13 (30.2%) cases of
      compressive neuropathies, 13 cases of hand/elbow tendinitis (30.2%) and 17 cases
      of shoulder tendinitis (39.5%). The average age of these 30 subjects was 47
      years, with a length of service of 23 years, mostly part-time workers.
      CONCLUSIONS: We found a high prevalence of general disorders and cases of UL
      WMSDs among the workers investigated, including part-time workers and workers who
      were not working exclusively as cashiers. The study also revealed a poor health
      surveillance programme to identify/ UL-WMSDs that should be the responsibility of
      the occupational physician and a consequent underestimation of risk and lack of
      the information needed to adopt preventive measures.

PMID- 23879068
TI  - [Chronicle of the Pomeranian Medical University in Szczecin for year 2010].

PMID- 23879069
TI  - [Scientific publications of the Pomeranian Medical University in Szczecin for
      year 2009].

PMID- 23879070
TI  - Tuberculosis care in 2013 and beyond: 20 years after the birth of the DOTS
      strategy.

PMID- 23879071
TI  - Estimation of the contribution of private providers in tuberculosis case
      notification and treatment outcome in Pakistan.
AB  - To improve involvement of the private sector in the national tuberculosis (TB)
      programme in Pakistan various public-private mix projects were set up between
      2004 and 2009. A retrospective analysis of data was made to study 6 different
      public-private mix models for TB control in Pakistan and estimate the
      contribution of the various private providers to TB case notification and
      treatment outcome. The number of TB cases notified through the private sector
      increased significantly from 77 cases in 2004 to 37,656 in 2009. Among the
      models, the nongovernmental organization model made the greatest contribution to
      case notification (58.3%), followed by the hospital-based model (18.9%).
      Treatment success was highest for the district-led model (94.1%) and lowest for
      the hospital-based model (74.2%). The private sector made an important
      contribution to the national data through the various public-private mix
      projects. Issues of sustainability and the lack of treatment supporters are
      discussed as reasons for lack of success of some projects.

PMID- 23879072
TI  - Effective gender-based violence screening tools for use in primary health care
      settings in Afghanistan and Pakistan: a systematic review.
AB  - Health care providers have an important role to play in the prevention and
      response to violence against women. However, the existing tools for screening for
      gender-based violence have been mostly formulated in the context of developed
      countries. This paper assesses which violence screening tools designed for use as
      the primary health care level would be feasible for use in Afghanistan and
      Pakistan, countries characterized by limited resources, unsupportive
      institutional frameworks and gender and social norms that reinforce domestic
      violence. A systematic review was made of the literature to evaluate the
      different screening instruments. The Women's Experience with Battering Scale
      (short version) and the Ongoing Violence Assessment Tool were judged to be the
      most useful tools for screening for violence against women in Afghanistan and
      Pakistan because they are short, S easy to administer and to score and respond to
      health care provider identified barriers of time and knowledge constraints for
      conducting screening for intimate partner violence.

PMID- 23879073
TI  - Parental involvement and bullying among middle-school students in North Africa.
AB  - Bullying, especially in developing countries, has not been much examined,
      especially the influence of parents on the risk of being bullied. The aim of this
      study was to determine whether active parenting is associated with reduced peer
      victimization among middle-school students in North Africa. A secondary analysis
      of data from more than 13,000 middle-school students who participated in the
      Global School-based Student Health Survey (GSHS) in Egypt, Libya, Morocco and
      Tunisia between 2006 and 2008, was conducted using multiple logistic regression
      models. About 60% of students in Egypt and one-third of students in Libya,
      Morocco and Tunisia reported having been bullied in the past month. In all 4
      countries, boys reported more peer victimization than girls. In Egypt, Morocco
      and Tunisia, students who reported that their parents checked their homework,
      were understanding, and knew how the student spent free time had a reduced
      likelihood of peer victimization but this association was not significant in
      Libya. Interventions for reducing bullying should consider the positive impact of
      involved parents.

PMID- 23879074
TI  - Ongoing deterioration of the nutritional status of Palestinian preschool children
      in Gaza under the Israeli siege.
AB  - This cross-sectional, community-based, household survey was carried out in Gaza
      City, Palestine during the first half of 2009 to study the nutritional status of
      Palestinian preschool children aged 2-5 years under blockade. The response rate
      was 95.2% from a total sample of 770. The majority (94.4%) of households faced
      difficulties accessing food, the main cause was the siege and the shortage of
      food products; and the majority (85.5%) were food insecure households. Just over
      50% of the preschoolers were anaemic, 26.8% of those who had a stool test had
      parasitic infections, and 15.0 were stunted. Food insecurity was the first
      predictor of stunting andd underweight, and malnutrition indicators indicate the
      worst situation in the Gaza Strip for several decades.

PMID- 23879075
TI  - Prevalence of and factors associated with obesity among Pakistani schoolchildren:
      a school-based, cross-sectional study.
AB  - Childhood obesity is nowadays a concern in the developing world. This cros
      sectional study was conducted on 501 randomly selected students from 10 high
      schools in an urban setting in Hyderabad, Pakistan. Children who were underweight
      were excluded. Interviews were conducted to determine demographic data, dietary
      intake, physical activity and other variables that may be associated with
      obesity. Overall 58 students (12%) had body mass index (BMI)>or=95th percentile,
      40 (8%) BMI>or=85th percentile and 403 (80%) had BMI<85th percentile (WHO age-
      and sex-specific cut-offs). The prevalence of obesity was higher in boys than
      girls (15% than 8% respectively). In multivariate regression analysis significant
      risk factors for obesity/overweight were male sex, middle socioeconomic status,
      poor self-rated athletic ability, trying to lose weight and eating fruit<4 times
      per week. Childhood obesity is determined by factors in the home, school and
      society and a multidisciplinary approach is needed to prevention.

PMID- 23879076
TI  - Assessment of suicidal and self-injurious behaviours among patients with
      depression.
AB  - The aim of this cross-sectional 1-year study was to estimate the prevalence and
      to identify the risk factors for suicidal and self-injurious behaviours among
      patients with depression. A convenience sample of 557 out- and inpatients
      diagnosed with mood disorders was selected from 3 treatment settings in Riyadh,
      Saudi Arabia. Eligible patients completed data on sociodemographic variables and
      the Columbia suicide severity rating scale risk assessment version. The reported
      prevalence of attempted suicide in the previous week was 36.6%, interrupted
      suicide attempt 29.8%, aborted suicide attempt 34.6% and self-injurious behaviour
      without suicide intent 7.7%. Concerning suicide ideation, 47.2% reported suicidal
      thoughts, 36.6% suicidal thoughts with methods but without a specific plan and
      35.4% suicidal intent without a specific plan. Male sex, joint family type,
      literate education, being in employment, smoking and physical co-morbidities were
      significantly associated with all types of suicide behaviour.

PMID- 23879077
TI  - Screening for BRCA1 large genomic rearrangements in female Egyptian hereditary
      breast cancer patients.
AB  - Approximately 5%-10% of all breast cancers are inherited as the result of
      germline mutations in the BRCAl gene. Large genomic rearrangements (LGRs) in
      BRCA1 have not been well-researched in the Egyptian population. Using multiplex
      ligation-dependent probe amplification, we showed BRCA1 rearrangements in 4/22
      cases (18.2%) of familial breast cancer. No influence of having multiple breast
      cancer cases within the family was observed in patients diagnosed at <or>or=45
      years and having BRCAl-positive LGRs. However, focusing on cases with first- and
      second-degree relatives affected, we observed a significant difference between
      the percentage of patients with BRCA1-positive versus BRCAl-negative LGRs. Our
      results provide the first evidence that LGRs in BRCA1 exist in the Egyptian
      population. Screening for these alterations may be desirable when breast cancer
      patients are diagnosed at an early age, especially if these cases have first- and
      second-degree of relatives with breast cancer.

PMID- 23879078
TI  - [Epidemiological and pathological features of cancer in Fez Boulemane region,
      Morocco].
AB  - In Fez-Boulemane, Morocco, there is no cancer registry so there is a lack of
      information about the incidence and characteristics of cancer in the region. In
      this retrospective study we examined the epidemiological and pathological
      features of 5532 cases of cancer collected from the Department of Pathology in
      Hassan II University Hospital of Fes from 2004 to 2010. The mean age of the
      patients was 53.5 years and 52% were male. Digestive cancers and skin cancers
      were the most common. Digestive cancers were predominantly colorectal and
      stomach. Cancers of the urinary bladder and colorectal cancers were the leading
      cancers in men accounting respectively for 9% and 8% of all male cancers. In
      women, cancers of the breast (62%) and uterine cervix (22.6%) predominated. As a
      first step in cancer control in our area, establishment of a regional cancer
      registry is recommended.

PMID- 23879080
TI  - [Food intake during the month of Ramadan in Moroccan patients with type 2
      diabetes].
AB  - This cross-sectional study aimed to assess the daily dietary intake of type 2
      diabetes patients attending Mohamed VI hospital in Marrakech during Ramadan 2010.
      Sociodemographic and clinical data were collected by interview, and qualitative
      and quantitative food intake, based on French nutritional tables, was assessed by
      a dietician. Of the 71 patients recruited, 55% were fasting. The average age of
      participants was 56.3 (SD 11,2) years. There were no statistically significant
      clinical differences between the fasting and nonfasting groups except for
      overweight/obesity and insulin dependence, which were more prevalent in the
      nonfasting group. The mean total daily caloric intake was significantly lower in
      the fasting than nonfasting group [1447.5 (SD 756.3) versus 1919.0 (SD 823.4)
      Kcal/d], as was the carbohydrate, lipid and protein intake. Carbohydrate intake
      was 57% and 56% of total calories. Overall during Ramadan the diet of the fasting
      group was calorie deficient and inadequate while for non-fasters it was
      excessive, which put them at risk of complications. Nutritional education may be
      needed for diabetic patients for Ramadan.

PMID- 23879079
TI  - Effect of zinc supplementation on serum zinc and calcium levels in postmenopausal
      osteoporotic women in Tabriz, Islamic Republic of Iran.
AB  - Research on the zinc status of osteoporotic women is scarce. This randomized,
      double-blind, placebo-controlled clinical trial assessed the effect of zinc
      supplementation on serum zinc and calcium levels in postmenopausal osteoporotic
      women. A sample of 60 women referred to a rheumatology clinic in Tabriz were
      randomly divided into intervention (220 mg zinc sulfate daily) and placebo
      groups. Anthropometric indices, dietary intake of zinc and calcium and serum zinc
      and calcium were assessed at baseline and after 60 days. Mean serum zinc
      concentrations were markedly lower than the normal range at baseline, but mean
      serum calcium levels were normal. In the intervention group serum levels were
      significantly higher after 60 days [120.5 (SD 7.5) versus 70.5 (SD 4.6)
      micrograms/dL] while serum calcium levels were unchanged [8.6 (SD 0.1) versus 9.1
      (SD 0.3) mg/dL]. The placebo group showed no significant changes in zinc or
      calcium levels. Postmenopausal osteoporotic women may benefit from zinc
      supplementation.

PMID- 23879081
TI  - Ocular disorders among schoolchildren in Khartoum State, Sudan.
AB  - From December 2005 to June 2007, a total screening of all 1418 government primary
      schools in Khartoum State, Sudan, was performed to estimate ocular problems among
      children aged 6-15 years. We screened 671,119 children (56.7% males) for
      significant refractive error and other eye ailments. Ocular problems were found
      in 20,321 (3.03%) children. The 3 localities with highest ocular pathology were
      Karary (26.2%), Ummbada (21.0%) and Jabal Awlia (15.7%). The overall prevalence
      of refractive error was 2.19%. Myopia was found in 10,064 (1.50%) children while
      4661 (0.70%) were hyperopic. Other ocular problems included vernal
      keratoconjunctivitis, vitamin A deficiency, microbial conjunctivitis, strabismus
      and corneal opacity. Only 288 (0.04%) children were diagnosed with active
      trachoma: 86.5% of these were from Ummbada locality, on the periphery ofthe
      State, where transportation facilities are poor and poverty is widespread.
      Overall, 99% of the eye ailments identified are either treatable or preventable.
      To reduce these and to achieve the goals of Vision 2020, an effective and
      efficient school health programme is needed.

PMID- 23879082
TI  - Possible health effects of liquefied petroleum gas on workers at filling and
      distribution stations of Gaza governorates.
AB  - Liquefied petroleum gas (LPG) is widely used in the Gaza Strip for domestic
      purposes, in agriculture and industry and, illegally, in cars. This study aimed
      to identify possible health effects on workers exposed to LPG in Gaza
      governorates. Data were collected by a questionnaire interview, and
      haematological and biochemical analyses of venous blood samples were made from 30
      workers at filling and distribution stations and 30 apparently healthy controls.
      Statistically significant differences were found in all self-reported health
      related complaints among LPG workers versus controls. LPG workers had
      significantly higher values of red blood cell counts, haemoglobin, haematocrit
      mean corpuscular haemoglobin and platelet counts. They also had significantly
      higher values of kidney function tests (urea, creatinine and uric acid) and liver
      function enzyme activities (aspartate aminotransferase and alanine
      aminotransferase). LPG workers at Gaza Strip petroleum stations are at higher
      risk for health-related symptoms and clinical abnormalities.

PMID- 23879083
TI  - Iraqi parents' views of barriers to childhood immunization.
AB  - Deficiencies in knowledge about immunization among parents often leads to poor
      utake or errors in immunization dosage and timing. The aims of this study were to
      determine Iraqi parents' views of barriers to immunization and beliefs about ways
      to promote immunization. A questionnaire survey was carried out among 528 Iraqi
      parents with children who had incomplete immunization status. The main barriers
      to immunization agreed by the parents were lack of vaccine availability (51.5% of
      parents) and parents' lack of education (42.4%), while 88.4% of parents thought
      that lack of funding was not an important barrier. More than 60% of the parents
      suggested promoting childhood immunization via the media, and 77.5% thought that
      an increase in funding would not remove barriers to childhood immunization.
      Better vaccine availability in public health clinics and improving parents'
      literacy might enhance immunization uptake in Iraq.

PMID- 23879084
TI  - Seventh TEPHINET Global Scientific Conference in Amman, Jordan, November 2012.
AB  - The Jordanian Ministry of Health in collaboration with the Eastern Mediterranean
      Public Health Network (EMPHNET) hosted the Seventh Global Scientific Conference
      of the Training Programs in Epidemiology and Public Health Interventions Network
      (TEPHINET) in Jordan in November 2012. This was the first time this Conference
      was held in the Eastern Mediterranean region. The Conference theme was
      "communicable and noncommunicable diseases: public health challenges and
      successes". Over 400 participants including field epidemiology training program
      residents, graduates and public health officials from 66 countries attended the
      Conference as well as 187 people from 57 countries who attended the conference
      sessions on line. The programme included 121 oral and 130 poster presentations in
      addition to 5 pre-conference workshops and 9 roundtable discussions. All sessions
      were recorded and virtually broadcasted and made available on line. The
      Conference succeeded in creating opportunities for dialogue between residents and
      graduates of field epidemiology training programmes and public health
      stakeholders across the region and the globe.

PMID- 23879085
TI  - [Experimental study of tissue engineered cartilage construction using oriented
      scaffold combined with bone marrow mesenchymal stem cells in vivo].
AB  - OBJECTIVE: To investigate the feasibility of fabricating an oriented scaffold
      combined with chondrogenic-induced bone marrow mesenchymal stem cells (BMSCs) for
      enhancement of the biomechanical property of tissue engineered cartilage in vivo.
      METHODS: Temperature gradient-guided thermal-induced phase separation was used to
      fabricate an oriented cartilage extracellular matrix-derived scaffold composed of
      microtubules arranged in parallel in vertical section. No-oriented scaffold was
      fabricated by simple freeze-drying. Mechanical property of oriented and non
      oriented scaffold was determined by measurement of compressive modulus. Oriented
      and non-oriented scaffolds were seeded with chondrogenic-induced BMSCs, which
      were obtained from the New Zealand white rabbits. Proliferation, morphological
      characteristics, and the distribution of the cells on the scaffolds were analyzed
      by MTT assay and scanning electron microscope. Then cell-scaffold composites were
      implanted subcutaneously in the dorsa of nude mice. At 2 and 4 weeks after
      implantation, the samples were harvested for evaluating biochemical,
      histological, and biomechanical properties. RESULTS: The compressive modulus of
      oriented scaffold was significantly higher than that of non-oriented scaffold
      (t=201.099, P=0.000). The cell proliferation on the oriented scaffold was
      significantly higher than that on the non-oriented scaffold from 3 to 9 days (P <
      0.05). At 4 weeks, collagen type II immunohistochemical staining, safranin O
      staining, and toluidine blue staining showed positive results in all samples, but
      negative for collagen type I. There were numerous parallel giant bundles of
      densely packed collagen fibers with chondrocyte-like cells on the oriented
      structure constructs. Total DNA, glycosaminoglycan (GAG), and collagen contents
      increased with time, and no significant difference was found between 2 groups (P
      > 0.05). The compressive modulus of the oriented tissue engineered cartilage was
      significantly higher than that of the non-oriented tissue engineered cartilage at
      2 and 4 weeks after implantation (P < 0.05). Total DNA, GAG, collagen contents,
      and compressive modulus in the 2 tissue engineered cartilages were significantly
      lower than those in normal cartilage (P < 0.05). CONCLUSION: Oriented
      extracellular matrix-derived scaffold can enhance the biomechanical property of
      tissue engineered cartilage and thus it represents a promising approach to
      cartilage tissue engineering.

PMID- 23879087
TI  - [Recombinant adenovirus Ad-human matrix metalloproteinase 1 transfecting bone
      marrow mesenchymal stem cells of rats in vitro].
AB  - OBJECTIVE: To transfect bone marrow mesenchymal stem cells (BMSCs) of rats by
      recombinant adenovirus Ad-human matrix metalloproteinase 1 (hMMP-1) in vitro so
      as to lay the experimental foundation for the treatment of liver fibrosis with a
      combination of BMSCs and hMMP-1 gene transplantation. METHODS: BMSCs were
      isolated from bone marrow of 2-3 weeks old Sprague Dawley rats by whole bone
      marrow adherence method and identified, then transfected by recombinant
      adenovirus Ad-hMMP-1 carrying enhanced green fluorescent protein (EGFP) marker in
      vitro. The green fluorescent expression was observed by fluorescence microscope
      and the transfection efficiency was detected by flow cytometry to determine the
      optimum multiplicity of infection (MOI). BMSCs at passage 3 were divided into 3
      groups: untransfected BMSCs group (group A), Ad-EGFP transfected BMSCs group
      (group B), and Ad-hMMP-1-EGFP transfected BMSCs group (group C); the gene and
      intracellular protein of hMMP-1 were detected by RT-PCR and Western blot; the
      ELISA assay was used to detect the supernatant protein expression, and the hMMP-1
      activity was measured by fluorescent quantification kit. RESULTS: The green
      fluorescent was observed in BMSCs transfected by recombinant adenovirus at 24
      hours after transfection; the fluorescence intensity was highest at 72 hours; and
      the optimum MOI was 200. The cells of 3 groups entered the logarithmic growth
      phase on the 3rd day and reached plateau phase on the 6th day by MTT assay; no
      significant difference was found in the cell proliferation rate among 3 groups (P
      > 0.05). RT-PCR, Western blot, and ELISA assay showed high expressions of the
      hMMP-1 gene and protein in group C, but no expression in groups A and B. The hMMP
      1 activity was 1.24 nmol/(mg.min) in group C, but hMMP-1 activity was not
      detectable in groups A and B. CONCLUSION: The exogenous hMMP-1 gene is
      successfully transfected into BMSCs of rats via recombinant adenovirus and can
      highly express, which lays the experimental foundation for the treatment of liver
      fibrosis with a combination of BMSCs and hMMP-1 gene transplantation.

PMID- 23879086
TI  - [Osteogenic effect of peptides anchored aminated tissue engineered bone for
      repairing femoral defect in rats].
AB  - OBJECTIVE: To study the osteogenic effects of a new type of peptides anchored
      aminated-poly-D, L-lactide acid (PA/PDLLA) scaffold in repairing femoral defect
      in rats. METHODS: The PDLLA scaffolds were treated by ammonia plasma and
      subsequent anchor of Gly-Arg-Gly-Asp-Ser (GRGDS) peptides via amide linkage
      formation. Thus PA/PDLLA scaffolds were prepared. The bone marrow was harvested
      from the femur and tibia of 4 4-week-old Sprague Dawley (SD) rats, and bone
      marrow mesenchymal stem cells (BMSCs) were isolated and cultured by whole bone
      marrow adherence method. BMSCs-scaffold composites were prepared by seeding
      osteogenic-induced BMSCs at passages 3-6 on the PA/PDLLA and PDLLA scaffolds. The
      right femoral defects of 8 mm in length were prepared in 45 adult male SD rats
      (weighing, 350-500 g) and the rats were divided into 3 groups (n=15) randomly.
      BMSCs-PA/PDLLA (PA/PDLLA group) or BMSCs-PDLLA (PDLLA group) composites were used
      to repair defects respectively, while defects were not treated as blank control
      (blank control group). General state of the rats after operation was observed. At
      4, 8, and 12 weeks after operation, general, radiological, histological, micro-CT
      observations and real-time fluorescent quantitative PCR were performed. RESULTS:
      Two rats died after operation, which was added; the other rats survived to the
      end of the experiment. At each time point after operation, general and
      radiological observations showed more quick and obvious restoration in PA/PDLLA
      group than in PDLLA group; no bone repair was observed in blank control group.
      The X-ray scores were the highest in PA/PDLLA group, higher in PDLLA group, and
      the lowest in blank control group; showing significant difference in multiple
      comparison at the other time (P < 0.05) except between blank control group and
      PDLLA group at 4 weeks (P > 0.05). The X-ray scores showed an increasing trend in
      PDLLA group and PA/PDLLA group with time (P < 0.05). Histological and micro-CT
      observations showed the best osteogenesis in PA/PDLLA group, better in PDLLA
      group, and worst in blank control group. Comparison between groups had
      significant differences (P < 0.05) in bone mineral density, bone volume/total
      volume of range of interest, trabecular number, and structure model index.
      Significant differences (P < 0.05) were found in the expression levels of
      osteogenesis-related genes, such as osteocalcin, alkaline phosphatase, collagen
      type I, bone morphogenetic protein 2, and osteopontin when compared PA/PDLLA
      group with the other groups by real-time fluorescent quantitative PCR analysis.
      CONCLUSION: The PA/PDLLA scaffolds can accelerate the repair of femoral defects
      in rats.

PMID- 23879088
TI  - [Construction of lentiviral vector containing Homo sapiens forkhead box C2 gene
      and its expression in bone marrow mesenchymal stem cells of rabbits].
AB  - OBJECTIVE: To construct the lentiviral vector containing Homo sapiens forkhead
      box C2 (Foxc2) gene and METHODS: Human Foxc2 gene coding to detect its expression
      in bone marrow mesenchymal stem cells (BMSCs) of rabbits. region fragment was
      obtained by RT-PCR and then cloned into the plasmid of LV-green fluorescent
      protein (GFP) to prepare Foxc2 lentiviral plasmid. Foxc2 lentiviral plasmid, pGC
      LV, pHelperl.0, and pHelper2.0 were co-transfected into 293T cells to obtain
      recombinant virus containing Foxc2 gene. The lentiviral titer was detected. BMSCs
      were isolated from bone marrow of rabbit and infected with Foxc2 recombined
      lentiviral, then the optimum multiplicity of infection (MOI) was determined by
      detecting the intensity of fluorescence expression. The expression of Foxc2 in
      the infected BMSCs was determined at 1, 3, and 7 days after transfection by
      inverted fluorescence microscope and Western blot. After osteogenic induction,
      Alizarin red staining was done to observe the formation of mineralized nodule.
      RESULTS: The Foxc2 recombinant lentiviral vector was constructed and was
      confirmed by restriction enzyme digestion and sequencing analysis. It could
      efficiently transfect 293T cells and express in 293T cells. The lentiviral titer
      was 2 x 10(8) TU/mL. The optimum MOI was 200. The inverted fluorescence
      microscope observation showed that the Foxc2 gene expressed in 84.5% +/-4.8% of
      infected BMSCs at 3 days after transfection. The expression of Foxc2 in infected
      BMSCs was stable and high, and increased gradually within 7 days after
      transfection by Western blot. At 2 weeks after osteogenic induction, Alizarin red
      staining showed that there were a large number of red calcified matrix deposition
      in the cytoplasm. CONCLUSION: Foxc2 recombined lentivirus with high viral titer
      is successfully constructed and packaged, and the Foxc2 gene can be transfected
      into BMSCs with stable and high expression of Foxc2 in infected cells, and these
      cellls may be applied for gene therapy of avascular necrosis of the femoral head.

PMID- 23879089
TI  - [Effects of chondroitinase ABC combined with bone marrow mesenchymal stem cells
      transplantation on repair of spinal cord injury in rats].
AB  - OBJECTIVE: To investigate the effects of chondroitinase ABC (ChABC) combined with
      bone marrow mesenchymal stem cells (BMSCs) in repair spinal cord injury of rats.
      METHODS: Primary BMSCs were isolated and cultured from the femur and tibia of
      neonatal Sprague Dawley (SD) rats. The spinal cord injury model was established
      in 24 adult SD male rats (weighing, 200-230 g), which were randomly divided into
      control group (group A), BMSCs transplantation group (group B), ChABC injection
      group (group C), and ChABC and BMSCs transplantation group (group D), 6 rats in
      each group. At 7 and 14 days after injury, Basso-Beattie-Bresnahan (BBB) score
      criteria was used to evaluate the hindlimb motor function; at 14 days after
      injury, the injured spinal cord tissue was perfused and stained by HE for further
      calculation of the injury area. Immunofluorescence staining were used for
      observing the expressions of glial fibrillary acidic protein (GFAP)/chondroitin
      sulfate proteoglycan (CSPG) and GFAP/growth associated protein 43 (GAP43).
      RESULTS: At 7 days after injury, three joints movement of the hindlimbs were
      recovered in all groups, and no significant difference in the BBB score was found
      among 4 groups (P > 0.05). At 14 days after injury, no load drag was observed in
      3 joints of the hindlimbs in groups A, B, and C, but weight-bearing plantar or
      occasional dorsalis pedis weight-bearing walking was observed in group D with no
      plantar walking. The BBB score of group D was significantly higher than that of
      the other 3 groups (P < 0.05). HE staining showed that the cavity formed in the
      damage zone, and there were a large number of macrophages in the cavity and its
      surrounding, which was wrapped by scar tissue. The damage area of group D was
      significantly smaller than that of the other 3 groups (P < 0.05). At 14 days
      after injury, the GFAP/CSPG double immunofluorescence staining showed that the
      astroglial scar damage zone in group D was significantly reduced, and no cavity
      formation was found. And the fluorescence intensity in groups C and D was
      significantly lower than that in group B (P < 0.05). The GFAP/GAP43 double
      immunofluorescence staining showed that GAP43-positive fibers passed through the
      damage zone in group D and the fluorescence intensity in group D was
      significantly higher than those in groups B and C (P < 0.05). CONCLUSION:
      Inhibition of astrocytes secreting CSPG by ChABC combined with BMSCs
      transplantation in early injury may promote the regeneration of nerve fibers, and
      repair spinal cord injury in rats.

PMID- 23879090
TI  - [Restoring phenotype of dedifferentiated normal nucleus pulposus cells by
      resveratrol].
AB  - OBJECTIVE: To investigate the effects of in-vitro monolayer culture and three
      dimensional (3-D) alginate microsphere culture on the differentiation of normal
      human nucleus pulposus cells (NPCs), and to discuss the regulatory mechanism of
      restoring the phenotype of dedifferentiated NPCs by culturing resveratrol (RES)
      in 3-D alginate microsphere. METHODS: Normal human nucleus pulposus tissues were
      harvested for culture and identification of NPCs from 6 patients with burst
      lumbar vertebra fracture. NPCs at passages 1, 3, 5, and 7 in the in-vitro
      monolayer culture were harvested to observe the morphology, cell aging, and
      proteoglycan expression. The cell proliferation rates of NPCs at passage 1 in
      vitro in monolayer culture and in 3-D alginate microsphere culture were detected.
      NPCs at passage 7 were randomly divided into 3-D alginate microsphere control
      group (group A), RES group (group B), silent mating type information regulation 2
      homolog 1 (SIRT1)- small interfering RNA (siRNA) + RES group (group C), and
      negative control-siRNA + RES group (group D); and NPCs in the in-vitro monolayer
      culture was monolayer control group (group E). After corresponding treatment,
      Western blot was used for determining the protein expressions of SIRT1, Aggrecan,
      and collagen type II; real-time fluorescence quantitative PCR was used for
      detecting SIRT1 mRNA expression. RESULTS: The cultured cells were identified to
      be NPCs. Morphological observation, senescence-associated P-galactosidase (SA-P
      gal) staining, and toluidine blue staining showed that dedifferentiation of
      normal NPCs tended to occur under continuous in-vitro monolayer culture, which
      was more obvious with increase of passage number. NPCs in 3-D alginate
      microsphere culture showed significantly lower proliferation rate than NPCs in
      the in-vitro monolayer culture (P < 0.05), but it could significantly improve the
      protein expressions of collagen type II and Aggrecan in dedifferentiated NPCs,
      showing significantly difference between groups E and A (P < 0.05). The protein
      expressions of SIRT1, collagen type II, and Aggrecan in group B were
      significantly improved when compared with that in group A (P < 0.05). Real-time
      fluorescence quantitative PCR and Western blot showed that the expressions of
      SIRT1 mRNA and proteins in group C were significantly inhibited after transfected
      with SIRT1-siRNA when compared with those in groups B and D (P < 0.05), and the
      protein expressions of collagen type II and Aggrecan in group C were
      significantly lower than those in groups B and D (P < 0.05). CONCLUSION:
      Continuous in-vitro monolayer culture could efficiently cultivate numerous
      seeding NPCs, but it is liable to dedifferentiate. In 3-D alginate microsphere
      culture, RES could restore the phenotype of dedifferentiated NPCs and synthesize
      more extracellular matrix, which is related to the regulation of SIRT1.

PMID- 23879091
TI  - [Bone marrow derived cells promoting pre-degeneration of sciatic nerve in vitro].
AB  - OBJECTIVE: To explore a new method for the pre-degeneration of peripheral nerve
      in vitro for obtaining many effective Schwann cells so as to provide a large
      number of seed cells for the research and application of tissue engineered
      nerves. METHODS: The bone marrow derived cells (BMDCs) from transgenic green
      fluorescent protein C57BL/6 mouse and the sciatic nerve segments from the C57BL/6
      mouse were co-cultured to prepare the pre-degeneration of sciatic nerve in vitro
      (experimental group, group A), and only sciatic nerve was cultured (control
      group, group B). At 7 days after culture, whether BMDCs can permeate into the
      sciatic nerve in vitro for pre-degeneration was observed by gross and
      immunohistofluorescence staining. And then Schwann cells were obtained from the
      sciatic nerves by enzymic digestion and cultured. The cell number was counted,
      and then the purity of primary Schwann cells was determined using
      immunohistofluorescence staining and flow cytometer analysis. RESULTS: At 7 days
      after pre-degeneration, gross observation showed that enlargement was observed at
      nerve stumps, and neuroma-like structure formed; the group A was more obvious
      than group B. Immunohistofluorescence staining showed many BMDCs permeated into
      the nerve segments, with positive F4/80 staining in group A. After culture, the
      yield of Schwann cells was (5.59 +/- 0.19) x 10(4) /mg in group A and (3.20 +/
      0.21) x 10(4)/mg in group B, showing significant difference (t=2.14, P=0.03). At
      48 hours after inoculation, the cells had blue bipolar or tripolar cell nuclei
      with small size and red soma by immunohistofluorescence staining; fibroblasts
      were flat polygonal with clear nucleus and nucleolus, showing negative p75NTR
      staining; and there were few of fibroblasts in group A. The purity of Schwann
      cells was 88.4% +/- 5.8% in group A and 76.1% +/-3.7% in group B, showing
      significant difference (t=2.38, P=0.04). And the flow cytometer analysis showed
      that the purity was 89.6% in group A and 74.9% in group B. CONCLUSION: BMDCs can
      promote the pre-degeneration of peripheral nerve in vitro, and it is a new method
      to effectively obtain Schwann cells for tissue engineered nerve.

PMID- 23879092
TI  - [Establishment of feeder-free culture system of human parthenogenetic embryonic
      stem cells].
AB  - OBJECTIVE: To establish a safe, effective, and economic feeder'-free culture
      system which is suitable for the culture of human parthenogenetic embryonic stem
      cells (hPESCs) in vitro. METHODS: hPESCs were cultured with mTeSR 1 medium
      (control group) and human foreskin fibroblasts-conditional medium (hFFs-CM)
      (experimental group). The growth status of hPESCs in both feeder-free culture
      systems were observed with inverted microscope. Alkaline phosphatase (ALP)
      analysis and karyotype analysis were used to study the biological characteristics
      of hPESCs. The expression of hPESCs pluripotent marker Oct-4 was analyzed by RT
      PCR. Differentiation experiment in vivo and in vitro was applied to observe the
      differentiation potential of hPESCs into three germ layers. RESULTS: hPESCs had
      regular morphology with difficulty in differentiation in both culture systems. No
      obvious difference was observed in morphology and expansion speed of hPESCs
      between 2 groups. After subcultured for 15 passages in vitro, hPESCs in 2 groups
      could maintain normal female diploid karyotype 46, XX and pluripotency. The
      expression of Oct-4 mRNA was positive in 2 groups. hPESCs in 2 groups could form
      embryonic body in differentiation experiment in vitro and could develop into
      teratomas containing three germ layers in nude mice. CONCLUSION: Feeder-free
      culture system of hFFs-CM can sustain the growth of hPESCs and keep hPESCs
      undifferentiated state for long. A feeder-free culture system of hPESCs is
      successfully established, which can support the growth of hPESCs, reduce the
      contamination from animals, decrease the cost of culture, and satisfy the
      clinical large-scale application.

PMID- 23879093
TI  - [Histomorphological and biomechanical characteristics of decellularized bovine
      tendons].
AB  - OBJECTIVE: To investigate the effect of repeated freezing and thawing combining
      nuclease treatment on the decellularization of bovine tendons, and the
      morphology, structure, biochemical compositions, and mechanical properties of the
      decellularized tendons. METHODS: A total of 48 fresh 1-day-old bovine Achilles
      tendons were randomly divided into 3 groups (n=16): fresh normal tendons (group
      A), repeated freezing and thawing for 5 times (liquid nitrogen refrigeration/37
      degreeC thawing, group B), and repeated freezing and thawing combining nuclease
      processing for 24 hours (group C). In each group, 2 tendons were used for
      scanning electron microscope (SEM), 3 tendons for histological and
      immunohistochemical observations, 3 tendons for DNA content detection, and 8
      tendons for biomechanical testing. RESULTS: SEM observation indicated the intact,
      aligned, and densely packed collagen fibers with no disruption in groups A and B,
      and the slightly loose collagen fibers with little disruption in group C. The
      alcian blue staining, sirius red staining, and immunohistochemical staining
      showed that the most of glycosaminoglycan, collagen type I, collagen type III,
      and fibronectin in group C were retained after decellularization treatment. HE
      and DAPI staining showed that the cell nuclei between the collagen fibers were
      clearly visible in groups A and B; however, the cell nuclei between collagen
      fibers almost were invisible with a few residual nuclei on the endotendineum in
      group C. DNA quantitative detection confirmed that DNA content in group C [(0.05
      +/-0.02) micr g/mg] was significantly lower than those in group A [(0.24 +/-0.12)
      micro g/mg] and group B [(0.16 +/-0.07) micro g/mg] (P < 0.05). Biomechanical
      testing showed that the values of tensile strength, failure strain, stiffness,
      and elastic modulus were different among 3 groups, but no significant difference
      was found (P > 0.05). CONCLUSION: Repeated freezing and thawing combining
      nuclease processing can effectively remove the component of cells, and
      simultaneously retain the original collagen fibrous structure, morphology, most
      of the extracellular matrix compositions, and mechanical properties of the bovine
      tendons.

PMID- 23879094
TI  - [Research progress of mesenchymal stem cells in burn wound repair].
AB  - OBJECTIVE: To review the research progress of mesenchymal stem cells (MSCs) in
      burn wound repair. METHODS: The recent literature about MSCs involved in burn
      wound repair and mechanism was extensively reviewed and analyzed. RESULTS: MSCs
      have the capacity of self-renew, rapid proliferation, differentiation and
      paracrine, and promote burn wound repair through differentiating into a series of
      skin wound cells and regulating wound microenvironment. CONCLUSION: MSCs have
      great potentials in the burn field. However, the cell survival and outcome are
      also facing challenges from poor microenvironment of the burn wound.

PMID- 23879095
TI  - [Research situation of stem cells transplantation for intervertebral disc
      degeneration].
AB  - OBJECTIVE: To summarize the research situation of stem cells transplantation for
      intervertebral disc (IVD) degeneration.degeneration. METHODS: The original
      articles about stem cells transplantation for repair of IVD degeneration were
      extensively reviewed; the clinical applications, the mechanisms, and related
      factors to influence repair effect were analyzed; and obstaclesreviewed; the
      clinical applications, the mechanisms, and related factors to influence repair
      effect were analyzed; and obstacles RESULTS: Autogenic stem cells transplantation
      can repair IVD degeneration and effectively relieve the symptoms of low back and
      leg pain. Stem cells can differentiate into disc chondrocytes in the disc
      microenvironment, increase the production of various growth factors, and exert a
      trophic effect on disc cells. It is also evident that the transplanted stem cells
      can potentially protect disc cells from apoptosis and maintain an immune
      privileged state in the IVD. Multiple factors such as tissue origin of stem
      cells, methods to pre-modulate the seeds, choice of injectable scaffolds, and
      even the severity of degeneration are closely related to the repair effects. To
      get a more efficient stem cell therapy, future researches are challenged to
      modulate the migration and distribution of stem cells in the IVD, avoid flow
      back, and better understand their ability to restore stemnness properties within
      the degenerative disc niche. CONCLUSION: Stem cells transplantation is proven to
      be a promising biological approach for repair of IVD degeneration.

PMID- 23879096
TI  - [Application of genipin for modification of natural biomaterials as a
      crosslinking agent].
AB  - OBJECTIVE: To review the application of genipin for the modification of natural
      biomaterials as a crosslinking agent and progress in research. METHODS: Domestic
      and foreign literature on application of genipin for the modification of natural
      biomaterials as a crosslinking agent was thoroughly reviewed. Results Genipin is
      an effective natural crosslinking agent with a very low level of cytotoxicity
      compared with conventional synthetic crosslinking agents. Tissues fixed with
      genipin can maintain a high level of stability as well as resistance to enzymatic
      degradation. CONCLUSION: Genipin is a promising substitute for conventional
      synthetic crosslinking agents, which has offered an alternative for modification
      of natural biomaterials for tissue engineering.

PMID- 23879097
TI  - [Surgical treatment of posteromedial corner injury combined with cruciate
      ligament rupture of knee].
AB  - OBJECTIVE: To investigate the methods and effectiveness of surgical treatment for
      posteromedial corner (PMC) injury combined with anterior cruciate ligament (ACL)
      and posterior cruciate ligament (PCL) ruptures. METHODS: Between February 2009
      and February 2012, 15 patients (15 knees) with PMC injury combined with ACL and
      PCL ruptures underwent PMC repair with suture anchor and ACL and PCL
      reconstruction. There were 7 males and 8 females with an average age of 39 years
      (range, 15-59 years). The causes of injury were traffic accident injury in 6
      cases, sport injury in 7 cases, and sprain injury in 2 cases. The disease
      duration was 3-15 days with an average of 7 days. All patients presented positive
      results of anterior drawer test, posterior drawer test and valgus stress test,
      and dysfunction of knee joint. Of 15 cases, 3 had ACL and PCL ruptures, 5 had ACL
      rupture, 3 had ACL injury at the attachment point of the condyles crest, and 4
      had PCL rupture; 9 had PMC tear at the femur insertion, 5 had PMC tear at the
      tibia insertion, and 1had PMC tear in the body area. RESULTS: All incisions
      healed by first intention with no complication of infection or stiffness of knee.
      All cases were followed up 18.4 months on average (range, 10-36 months). At last
      follow-up, 14 cases had normal knee flexion and extension ranges, but 1 case had
      10 degree limitation of the knee extension. Except 1 case which had weakly
      positive valgus stress test, the other patients showed negative results of
      anterior drawer test, posterior drawer test, and valgus stress test. Based on the
      improved Lysholm classification standard, the results were excellent in 8 cases,
      good in 5 cases, and fair in 2 cases; the excellent and good rate was 86.7%.
      CONCLUSION: Early repair of the PMC and reasonable reconstruction of cruciate
      ligament can effectively restore the knee stability for patients with PMC injury
      combined with ACL and PCL ruptures.

PMID- 23879098
TI  - [Arthroscopically assisted treatment of acute tibial insertion avulsion fracture
      of posterior cruciate ligament via posteromedial incision].
AB  - OBJECTIVE: To investigate the effectiveness of arthroscopically assisted
      treatment of acute tibial insertion avulsion fracture of the posterior cruciate
      ligament (PCL) via posteromedial incision. METHODS: Between January 2010 and
      January 2012, 22 patients with acute tibial insertion avulsion of the PCL
      underwent arthroscopic reduction and fixation via posteromedial incision. There
      were 14 males and 8 females with an average age of 32 years (range, 18-48 years).
      The injury causes included traffic accident injury in 14 cases, sport injury in 4
      cases, and falling injury in 4 cases. The disease duration ranged from 7 to 16
      days (mean, 10 days). Of 22 patient, 14 had simple PCL injury, 6 had PCL injury
      with meniscus injury, and 2 with cartilage injury. The results of posterior
      drawer test were positive in all patients. The preoperative Lysholm score was
      51.1 +/-3.4. RESULTS: All incisions healed by first intention without infection,
      deep venous thrombosis of lower limbs, or vessel and nerve injuries. All patients
      were followed up 12-24 months (mean, 18.4 months). X-ray films showed that all
      fractures healed with the healing time of 2-4 months (mean, 3 months). The
      Lysholm score was improved to 96.0 +/-2.2 at 6 months after operation, showing
      significant difference when compared with preoperative score (t=43.020, P=0.000).
      CONCLUSION: Arthroscopically assisted treatment of acute tibial insertion
      avulsion fracture of the PCL via posteromedial incision is a safe, easy, and
      effective method.

PMID- 23879099
TI  - [Medium-term effectiveness of total hip arthroplasty with straight tapered
      rectangular femoral prosthesis].
AB  - OBJECTIVE: To investigate the medium-term effectiveness of straight tapered
      rectangular femoral prosthesis in total hip arthroplasty (THA). METHODS: Between
      May 2004 and June 2006, 58 cases (61 hips) of hip joint disease underwent THA
      with straight tapered rectangular femoral prosthesis and the clinical data of 43
      cases (45 hips) followed up more than 6 years were retrospectively analyzed.
      There were 21 males (23 hips) and 22 females (22 hips) with an average age of
      51.6 years (range, 25-75 years), including 12 cases (12 hips) of congenital
      developmental dysplasia of the hip, 1 case (1 hip) of osteoarthritis secondary to
      acetabular dysplasia, 1 case (1 hip) of hip deformity after poliomyelitis, 9
      cases (9 hips) of femoral neck fractures, 8 cases (8 hips) of avascular necrosis
      of the femoral head, 8 cases (8 hips) of osteoarthritis of the hip joint, 2 cases
      (3 hips) of rheumatoid arthritis, and 2 cases (3 hips) of ankylosing spondylitis.
      Unilateral replacement was performed in 41 cases and bilateral replacement in 2
      cases. The Harris score was 41.7 +/-10.4 before operation. X-ray examination was
      performed to analyze the location of femoral prostheses and evaluate the
      stability of the prosthesis-bone interface, and Harris score was used to evaluate
      the hip function. RESULTS: Periprosthetic fracture occurred in 3 hips, and thigh
      pain in 4 hips after operation. Forty-three cases (45 hips) were followed up 74
      99 months (mean, 85 months). Harris score was 87.6 +/- 8.3 at last follow-up,
      showing significant difference when compared with preoperative score (t=23.14,
      P=0.00). The X-ray examination showed that 9 hips had heterotopic ossification;
      bone resorption caused by stress shielding was observed at the proximal femur in
      42 hips. But the stability of the prosthesis-bone interface was good; no
      infection or dislocation occurred; and no revision for aseptic loosening was
      performed in all cases. The survival rate of the femoral prosthesis was 100%
      during medium-term follow-up. CONCLUSION: THA with straight tapered rectangular
      femoral prosthesis has good medium-term effectiveness.

PMID- 23879100
TI  - [Nuss procedure by thoracoscopy for minimally invasive correction of pectus
      excavatum].
AB  - OBJECTIVE: To summarize the effectiveness of Nuss procedure by thoracoscopy for
      correction of pectus excavatum. METHODS: Between September 2009 and January 2012,
      33 patients suffering from pectus excavatum underwent Nuss procedure by
      thoracoscopy. There were 26 males and 7 females, aged from 3 to 22 years (median,
      9 years). There was primary operation in 32 cases and reoperation in 1 case after
      Ravitch procedure. Twenty-four patients had obvious clinical symptoms. The Haller
      index ranged from 3.3 to 50.1 (mean, 5.6). According to simplified Park
      classification, 25 cases were classified as symmetric type, 5 as eccentric type,
      and 3 as unbalanced type. RESULTS: Intercostal muscle tear occurred in 1 case
      during operation; pleural effusion, pulmonary infection, and thoracic vertebral
      pain occurred in 1 case, respectively after operation. The operation time ranged
      from 38 to 89 minutes (mean, 60.9 minutes). The intraoperative blood loss was 8
      90 mL (mean, 26.2 mL). The postoperative hospitalization days were 6-12 days
      (mean, 7.6 days). All patients were followed up 12-39 months (mean, 25.6 months).
      Electrocardiogram and chest X-ray film showed that cardiac compression was
      improved, and symptoms alleviated. At the last follow-up, according to the Nuss
      standard, the results were excellent in 27 cases, good in 3 cases, and fair in 3
      cases, with an excellent and good rate of 90.9%. There was no significant
      difference in results of effectiveness evaluation among less than 6 years, 6-12
      years, and more than 12 years groups (Z= -1.751, P=0.109). CONCLUSION: Nuss
      procedure by thoracoscopy has the advantages of little trauma, simple operation,
      and fast recovery, so it can obtain satisfactory correction of pectus excavatum.

PMID- 23879101
TI  - [Repair of severe nail bed defects with radial dorsal fasciocutaneous flap of
      thumb].
AB  - OBJECTIVE: To summarize the effectiveness of radial dorsal fasciocutaneous flap
      of thumb for repairing severe nail bed defects. METHODS: Between May 2009 and
      January 2012, 16 patients with severe nail bed defect were treated with radial
      dorsal fasciocutaneous flap of the thumb. There were 10 males and 6 females, aged
      16-54 years (mean, 36 years). The causes of injury included crush injury in 10
      cases, chainsaw injury in 4 cases, and scald in 2 cases; injured fingers were
      thumb in 3 cases, index finger in 4 cases, middle finger in 5 cases, ring finger
      in 3 cases, and little finger in 1 case. The time between injury and operation
      was 2 hours to 8 days (mean, 19.3 hours). Of 16 patients, 9 complicated by distal
      phalanx fracture. The area of defect ranged from 0.9 cm x 0.6 cm to 2.3 cm x 2.1
      cm. According to ZHOU Qingwen's grading system for nail bed defects, 6 cases were
      rated as degree III and 10 cases as degree IV. The area of flap ranged from 1.0
      cm x 0.6 cm to 2.5 cm x 2.2 cm. Retrograde transposition was performed to repair
      the thumb defect, and pedicled transposition to repair the 2nd-5th fingers
      defects. The donor sites were directly sutured or were repaired with skin graft.
      RESULTS: All flaps and skin grafts survived, and wounds healed by first
      intention. All patients were followed up 6-12 months (mean, 8 months). The color,
      texture, and contour of the flaps were good. According to total active motion
      standard, the finger function was assessed as excellent in 10 cases, good in 4
      cases, and fair in 2 cases, and the excellent and good rate was 87.5%.
      CONCLUSION: Radial dorsal fasciocutaneous flap of thumb is a reliable flap with
      easy dissection and less trauma in repair of severe nail bed defects.

PMID- 23879102
TI  - [Biomechanical effects of iliac screw plates on stability of lumbo-iliac fixation
      construct].
AB  - OBJECTIVE: To evaluate the biomechanical effect of a self-made iliac screw plate
      on the stability of lumbo-iliac fixation construct before and after fatigue
      loading. METHODS: Twelve fresh lumbo-pelvic specimens from donated adult cadavers
      with formalin embalm were used in the study. According to whether use the iliac
      screw plate or not, the specimens were randomly assigned into group A (with iliac
      screw plate, n=6) and group B (without iliac screw plate, n=6). The bone mineral
      density (BMD) of L(t-4) was measured using dual-energy radiograph absorptiometry.
      The pedicle screw and iliac screw fixation were given at L3-5, and bilateral
      facetectomy and diskectomy at L5, S1 level were performed to prepare the model of
      the intervertebral destabilization. The biomechanical testing was conducted on a
      material testing machine under 0-600 N compression and -7-7 N.m torsion loading
      modes for the initial compressive stiffness and torsional stiffness evaluation.
      And then 20 000 cyclic compressive loading of 40-400 N was given to the specimen,
      the stiffness evaluation was repeated. Then the maximum pull-out strength of
      screws at every level was measured and compared. Gross observation and
      radiological observation were performed during experiment. RESULTS: The BMD
      values of groups A and B were (1.15 +/-0.13) g/cm(2) and (1.12 +/-0.11) g/cm(2)
      respectively, showing no significant difference between 2 groups (t=0.428,
      P=0.678). All pedicle screws and iliac screws were inserted in good position; no
      loosening or breaking of screw was observed during loading. After fatigue
      loading, the incidence of halo ring around the iliac screws of groups A and B was
      16.7% (1/6) and 50.0% (3/6), respectively. The compressive stiffness and
      torsional stiffness after fatigue loading were significantly lower than those in
      initial state in groups A and B (P < 0.05); there was no significant difference
      in compressive stiffness and torsional stiffness between groups A and B before
      fatigue loading (P > 0.05). However, group A had higher compressive stiffness
      than group B (t=2.664, P=0.024) after fatigue loading, and there was no
      significant difference in torsional stiffness between 2 groups (t=0.410,
      P=0.690). No significant difference was found in screw pull-out strength of
      pedicle screws at L3, L4, and L5 levels between groups A and B (P > 0.05);
      however, the pull-out strength of the iliac screws in group A was significantly
      higher than that in group B (t=3.398, P=0.007). In groups A and B, the pull-out
      strength of L3 screw was significantly lower than that of L4 and L5 screws (P <
      0.05). In group A, pull-out strength of the iliac screws was significantly higher
      than that of L3, L4, and L5 screws (P < 0.05); in group B, the pull-out strength
      of iliac screws was significantly lower than that of L4 and L5 screws (P < 0.05).
      CONCLUSION: In the lumbo-iliac reconstruction, the use of iliac screw plate could
      resist iliac screw loosening, therefore, it has the potential to increase the
      stability oflumbo-iliac fixation construct.

PMID- 23879103
TI  - [Biocompatibility of silicon containing micro-arc oxidation coated magnesium
      alloy ZK60 with osteoblasts cultured in vitro].
AB  - OBJECTIVE: To research in vitro biocompatibility of silicon containing micro-arc
      oxidation (MAO) coated magnesium alloy ZK60 with osteoblasts. METHODS: The
      surface microstructure of silicon containing MAO coated magnesium alloy ZK60 was
      observed by a scanning electron microscopy (SEM), and chemical composition of the
      coating surface was determined by energy dispersive spectrum analysis. The
      experiments were divided into 4 groups: silicon containing MAO coated magnesium
      alloy ZK60 group (group A), uncoated magnesium alloy ZK60 group (group B),
      titanium alloy group (group C), and negative control group (group D). Extracts
      were prepared respectively with the surface area to extraction medium ratio (1.25
      cm(2)/mL) according to ISO 10993-12 standard in groups A, B, and C, and were used
      to culture osteoblasts MC3T3-E1. The a-MEM medium supplemented with 10% fetal
      bovine serum was used as negative control in group D. The cell morphology was
      observed by inverted phase contrast microscopy. MTT assay was used to determine
      the cell viability. The activity of alkaline phosphatase (ALP) was detected. Cell
      attachment morphology on the surface of different samples was observed by SEM.
      The capability of protein adsorption of the coating surface was assayed, then
      DAPI and calcein-AM/ethidium homodimer 1 (calcein-AM/EthD-1) staining were
      carried out to observe cell adhesion and growth status. RESULTS: The surface
      characterization showed a rough and porous layer with major composition of Mg, O,
      and Si on the surface of silicon containing MAO coated magnesium alloy ZK60 by
      SEM. After cultured with the extract, cells grew well and presented good shape in
      all groups by inverted phase contrast microscopy, group A was even better than
      the other groups. At 5 days, MTT assay showed that group A presented a higher
      cell proliferation than the other groups (P < 0.05). Osteoblasts in groups A and
      C presented a better cell extension than group B under SEM, and group A exhibited
      better cell adhesion and affinity. Protein adsorption in group A [ (152.7 +/-
      6.3) microg/mL] was significantly higher than that of group B [(96.3 +/-3.9)
      microg/mL] and group C [ (96.1 +/-8.7) microg/mL] (P < 0.05). At each time point,
      the adherent cells on the sample surface of group A were significantly more than
      those of groups B and C (P < 0.05). The calcein-AM/EthD-1 staining showed that
      groups A and C presented better cell adhesion and growth status than group B. The
      ALP activities in groups A and B were 15.55 +/-0.29 and 13.75 +/-0.44
      respectively, which were significantly higher than those in group C (10.43 +/
      0.79) and group D (10.73 +/-0.47) (P < 0.05), and group A was significantly
      higher than group B (P < 0.05). CONCLUSION: The silicon containing MAO coated
      magnesium alloy ZK60 has obvious promoting effects on the proliferation,
      adhesion, and differentiation of osteoblasts, showing a good biocompatibility, so
      it might be an ideal surface modification method on magnesium alloys.

PMID- 23879104
TI  - [A preliminary study on vascular endothelial growth factor C gene modified lymph
      node transplantation in promoting proliferation of lymphatic endothelial cells].
AB  - OBJECTIVE: To investigate the effects of vascular endothelial growth factor C
      (VEGF-C) gene modified lymph nodes on promoting proliferation of lymphatic
      endothelial cells in the surrounding tissues. METHODS: Thirty-six Sprague Dawley
      rats, weighing 200.1-271.5 g, were randomly divided into 2 groups (n=18). After
      the in situ axillary lymph nodes transplantation models were established in both
      groups, 1.5 x 10(8) PFU Ad-VEGF-C-Flag and Ad-Flag were injected into the
      transplanted lymph nodes in experimental group and control group, respectively.
      At 3 days after injection, the axillary lymph nodes were harvested to observe the
      expression of Flag; at 1, 2, and 4 weeks after injection, the axillary lymph
      nodes and the surrounding tissues were harvested to observe the expression of
      Prxo-1 protein and to calculate the fluorescence density; at 2 and 4 weeks after
      injection, the absorbance (A) value of treated blood at 620 nm was calculated to
      observe lymphatic backflow function improvement; the rats without treatment
      served as normal control group, and the rats with in situ axillary lymph RESULTS:
      At 3 days after injection, the expression of Flag could be nodes transplantation
      model served as blank control group. detected in experimental group and control
      group. The fluorescence density of Prox-1 protein in experimental group increased
      at 1, 2, and 4 weeks, and it was significantly higher than that in control group
      (P < 0.05). The A values of normal control group and blank control group were
      0.539 +/-0.020 and 0.151 +/- 0.007, respectively. The A values of experimental
      group and control group were 0.170 +/- 0.011 and 0.168 +/- 0.010 at 2 weeks, and
      0.212 +/- 0.016 and 0.197 +/- 0.006 at 4 weeks, which were significantly lower
      than those of normal control group (P < 0.05), but no significant difference was
      found when compared with blank control group, and between the experimental group
      and control group (P > 0.05). CONCLUSION: The VEGF-C gene modified lymph nodes
      can stimulate the proliferation of lymphatic endothelial cells in the surrounding
      tissues. However, it has no improved effect on lymphatic back-flovi function in
      the affected limb.

PMID- 23879105
TI  - [Experimental study on hemostasis of thermosensitive chitosan hemostatic film].
AB  - OBJECTIVE: To investigate the hemostasis of thermosensitive chitosan hemostatic
      film. METHODS: Fifty adult Sprague Dawley rats, male or female and weighing 190
      210 g, were made the models of liver injury. The models were randomly divided
      into 5 groups (n=10) depending on different hemostatic materials. The incision of
      the liver was covered with the hemostatic materials of 2.0 cm x 1.0 cm x 0.5 cm
      in size: thermosensitive chitosan hemostatic film (group A), chitosan hemostatic
      film (group B), cellulose hemostatic cotton (group C), gelatin sponge (group D),
      and no treatment (group E), respectively. The bleeding time and bleeding amount
      were recorded. After 4 weeks, the incisions of the liver were observed with HE
      staining. RESULTS: Gross observation showed better hemostatic effect and faster
      hemostatic time in groups A, B, and C; group D had weaker hemostatic effect and
      slower hemostatic time; group E had no hemostatic effect. The bleeding time and
      bleeding amount of groups A, B, C, and D were significantly lower than those of
      group E (P < 0.05). The bleeding time and bleeding amount of groups A, B, and C
      were significantly lower than those of group D (P < 0.05), but no significant
      difference was found among groups A, B, and C (P > 0.05). The liver cells of
      group A had milder edema and ballooning degeneration than other 4 groups through
      histological observation. CONCLUSION: The thermosensitive chitosan hemostatic
      film has good hemostasis effect on the liver incision of rats.

PMID- 23879106
TI  - [Progress in treatment of acute achilles tendon rupture].
AB  - OBJECTIVE: To review the progress in the treatment of acute Achilles tendon
      rupture. METHODS: Recent literature about the treatment of acute Achilles tendon
      rupture was reviewed and analyzed. RESULTS: Treatments of acute Achilles tendon
      rupture include operative and non-operative treatments. Operative treatments
      include open surgery and percutaneous minimally invasive surgery. Compared with
      non-operative treatment, operative treatment can effectively reduce the re
      rupture incidence, but it had higher complication incidences of wound infection
      and nerve injury. Although early functional rehabilitation during non-operative
      treatment could reduce the re-rutpture incidence, there is no consistent
      orthopaedic device and guideline for functional rehabilitation. CONCLUSION: Both
      operative and non-operative treatments have advantages and disadvantages for the
      treatment of acute Achilles tendon rupture. No consistent conclusion is arrived
      regarding functional recovery. Future studies should explore the strategy of
      early functional rehabilitation during non-operative treatment and its mechanism
      of promoting tendon healing.

PMID- 23879107
TI  - [Research progress of mechanism and prevention of peritendinous adhesions].
AB  - OBJECTIVE: To review the research progress of mechanism and prevention of
      peritendinous adhesions. Methods Recent literature about peritendinous adhesions
      was reviewed, and the results from experiments about the mechanism and prevention
      of peritendinous adhesions were analyzed. RESULTS: The molecular mechanism of
      peritendinous adhesions is related to overexpressions of transforming growth
      factor beta 1, early growth response protein 1, matrix metallopeptidase 9, and so
      on. The present methods of prevention of peritendinous adhesions include drugs,
      barrier, optimizing rehabilitation, gene therapy, and so on. These methods have
      achieved good results in experiments, but the clinical applications have not been
      confirmed yet. CONCLUSION: It is necessary to pay more attention to the research
      of mechanism of peritendinous adhesions and methods of its prevention and
      subsequently to convert them into clinical applications, which is significant to
      the prevention of peritendinous adhesions in the future.

PMID- 23879108
TI  - Interprofessional learning: from team mate to class mate.

PMID- 23879109
TI  - Interprofessional learning: case studies. Move out of the comfort zone.

PMID- 23879110
TI  - Research: winners in the varsity match.

PMID- 23879111
TI  - Research: case studies. Baby steps to better practice.

PMID- 23879112
TI  - Career development: ladders that we can all climb.

PMID- 23879113
TI  - Career development: case studies. 'Curiosity goes through the roof'.

PMID- 23879114
TI  - Leadership: no more heroes any more.

PMID- 23879115
TI  - Clinical correspondence: time to do better with a letter.

PMID- 23879116
TI  - Preventing pressure ulcers in acute care: facing up to painful truths.

PMID- 23879117
TI  - Pressure ulcers: case studies piling the pressure on the problem.

PMID- 23879118
TI  - Workforce compliance: ensuring temporary is trusted.

PMID- 23879119
TI  - Workforce compliance: case studies putting the checks in the post.

PMID- 23879120
TI  - Workforce: why a new act needs a new script.

PMID- 23879121
TI  - Robert francis interview: the NHS is some way from honest with itself.

PMID- 23879122
TI  - Payment system set for major overhaul.

PMID- 23879123
TI  - 'Expedia' system for appointments.

PMID- 23879124
TI  - The never-ending emergency 'peak': the NHS's acute care strategy isn't working.

PMID- 23879126
TI  - Public health must lead a public system.

PMID- 23879125
TI  - Overcoming the barriers to integrated care.

PMID- 23879127
TI  - Commissioning: show me the way to consistent clinical care.

PMID- 23879128
TI  - Technology: taking the paper out of paperwork.

PMID- 23879129
TI  - Mental health: making leaders of staff and patients.

PMID- 23879130
TI  - Exporting innovation: part 2 of 2. Fulfilling Eastern promise.

PMID- 23879132
TI  - Commissioning: GP and giving manager partnership CCGs robustness to lead.

PMID- 23879131
TI  - Engagement: do you want to be in my gang?

PMID- 23879133
TI  - CCG frustration in new system.

PMID- 23879134
TI  - We will facilitate change, not hinder it.

PMID- 23879135
TI  - The catch-22 in A&E funding.

PMID- 23879136
TI  - Equipment maintenance: rise of the machines.

PMID- 23879137
TI  - Equipment maintenance: case studies don't just tick the renewal box.

PMID- 23879138
TI  - Workforce: mind the skills gap.

PMID- 23879139
TI  - Workforce: case studies safe pairs of hands.

PMID- 23879140
TI  - Pathology: good neighbours.

PMID- 23879141
TI  - Pathology: case studies tube connection.

PMID- 23879142
TI  - Service redesig:n share dividends.

PMID- 23879143
TI  - Estates management: Francis hits a nerve.

PMID- 23879144
TI  - Diagnostics: testing times.

PMID- 23879145
TI  - Self care: do it yourself.

PMID- 23879146
TI  - Self care: case studies American dream.

PMID- 23879147
TI  - Inventory management: time to take stock seriously.

PMID- 23879148
TI  - Inventory management: case studies now where did i put that.

PMID- 23879150
TI  - Governance: time to invite new talent to the table.

PMID- 23879149
TI  - Social media: pledges show that going viral works.

PMID- 23879151
TI  - Public engagement: the battle for hearts and minds.

PMID- 23879152
TI  - Volunteering: more than a helping hand.

PMID- 23879153
TI  - Commissioning: 100 days of incertitude.

PMID- 23879154
TI  - The NHS pay bill needs to be reformed alongside services.

PMID- 23879155
TI  - Care Bill proposals won't improve safety.

PMID- 23879156
TI  - Taking safety seriously.

PMID- 23879157
TI  - Back to the NHS front line.

PMID- 23879158
TI  - Grasping a vital safety message.

PMID- 23879160
TI  - Patient data: why caring is desperate for sharing.

PMID- 23879159
TI  - Infection control: case studies hands-on tips to beat bacteria.

PMID- 23879161
TI  - Patient data: case studies meet the record breakers.

PMID- 23879162
TI  - Stroke: the peer review scheme that is improving care.

PMID- 23879163
TI  - Acute care: the numbers don't add up.

PMID- 23879164
TI  - Commissioning: aiming for a gold standard of care.

PMID- 23879165
TI  - Governance: achieving a sense of balance.

PMID- 23879166
TI  - Delivery of paclitaxel and berbamine by polymeric carriers to cure gastric
      cancer.
AB  - Successful chemotherapy needs to reduce the toxic side effects against normal
      tissues and avoid the detriments caused by intolerable solvents. Drug delivery
      systems using soluble polymeric nanoparticles tend to be the focus. In the
      current study, core-shell structure nanoparticles were prepared from block
      copolymer of methoxy poly(ethylene glycol)-polycaprolactone (mPE-PCL). Paclitaxel
      (PTX) and berbamine (BA) were incorporated into mPEG-PCL nanoparticles. It was
      found in our study that PTX and BA can be incorporated into the nanoparticles
      with high encapsulation efficiency. In vitro release study showed that PTX and BA
      were released from nanoparticles in a sustained manner. In vitro cytotoxicity
      studies indicated that PTX/BA coloaded nanoparticles (PTX/BA-np) show dose- and
      time-dependent cytotoxicity again BGC823 cells. Furthermore, intratumoral
      administration was applied to improve the tumor-targeted delivery in the in vivo
      evaluation. Compared with free drugs, PTX/BA-np exhibited superior antitumor
      effect by delaying tumor growth when delivered intratumorally. These results
      suggest that PTX/BA-np are effective to inhibit the growth of human gastric
      cancer and merit more research to evaluate the feasibility of clinical
      application.

PMID- 23879167
TI  - In vitro repolarized tumor macrophages inhibit gastric tumor growth.
AB  - Gastric cancer is the second most frequent cause of cancer-related death
      worldwide. Combined surgery and chemo/radiotherapy give only a limited 5-year
      survival rate. Alternative therapeutic strategies such as immunotherapy are
      needed to improve this survival rate. Macrophages are functionally plastic cells.
      Type 1 macrophages (M1) inhibit, whereas type 2 macrophages (M2) promote, tumor
      growth. In this study, we examined the effects of in vitro repolarized tumor
      macrophages on gastric tumor growth in vivo. We demonstrated that peritoneal
      macrophages isolated from mouse forestomach carcinoma (MFC) tumor-bearing mice
      (TPM) displayed a M2 functional phenotype as indicated by a characteristic
      cytokine production profile and expression pattern of inducible nitric oxide
      synthase (iNOS) and arginase (Arg) of M2 macrophages. Treatment of TPM with type
      1 cytokine IL-12 and IFN-gamma repolarized TPM toward the M1 phenotype as
      confirmed by a cytokine production profile and expression pattern of iNOS and Arg
      of typical M1 macrophages. Repolarized TPM significantly inhibits the growth of
      MFC tumors implanted subcutaneously compared to peritoneal macrophage (PM)
      isolated from normal animals, TPM, or M2 macrophages. Our study supports in vitro
      repolarization of macrophages as a potential immunotherapeutic strategy for
      gastric cancer.

PMID- 23879168
TI  - Alterations of axis inhibition protein 1 (AXIN1) in hepatitis B virus-related
      hepatocellular carcinoma and overexpression of AXIN1 induces apoptosis in
      hepatocellular cancer cells.
AB  - Axis inhibition protein 1 (AXIN1) is a negative regulator of Wnt/beta-catenin
      signaling via regulating the level of beta-catenin. However, the role of AXIN1 in
      the tumorigenesis and progression of hepatitis B virus (HBV)-related
      hepatocellular carcinoma (HCC) is less clear. PCR sequence analysis,
      immunohistochemistry, and Western blot were performed on 22 HBV-related HCC
      samples and corresponding nontumor liver tissues to detect variants in AXIN1 gene
      and the expression level of AXIN1. Human hepatoma cell lines SNU475 and SNU423
      were transfected with pCDNA3.1-AXIN1-myc or AXIN1 G425S-myc mutant. The growth
      curve and apoptosis rate of cell lines, phosphorylation of beta-catenin, and cell
      cycle regulatory proteins depending on beta-catenin transcriptional activity were
      detected. We identified four mutations of AXIN1 in 22 primary HBV-related HCCs
      and demonstrated a lower expression of AXIN1 in HBV-related HCC tissues than that
      in paired adjacent nontumor tissues. Overexpression of AXIN1 wild-type but not
      AXIN1 mutant inhibited the growth of HCC cell lines, accelerated their apoptosis,
      and negatively regulated beta-catenin-dependent transcriptional activity. Our
      study revealed that alterations of AXIN1 were involved in HBV-related HCC.
      Overexpression of AXIN1 but not AXIN1 mutant negatively regulated beta-catenin
      dependent transcriptional activity and downregulated the level of cell cycle
      regulatory proteins, suggesting that AXIN1 may be a potential target for gene
      therapy of primary HCC.

PMID- 23879169
TI  - In vivo selection of high-metastatic subline of bladder cancer cell and its
      characterization.
AB  - The majority of deaths associated with solid tumors are caused by tumor
      metastasis. To prevent metastasis, it is vital to understand its detailed
      process. In hematogenous metastasis of bladder cancer, some cancer cells
      disseminating into blood circulation extravasate into the lung tissues to form
      metastases. To study the molecular basis of the lung metastasis of bladder
      cancer, we employed an in vivo selection system that mimics hematogenous
      metastasis of bladder cancer on a low-metastatic bladder cancer cell line (KK
      47). We have successfully isolated a high-metastatic bladder cancer subline, KK
      47HM4, from KK-47 cells. We characterized KK-47HM4 in in vitro experimental
      systems. No significant difference in growth rate and susceptibility to NK cell
      attack between KK-47 and KK-47HM4 cells was observed. However, KK-47HM4 exhibited
      the higher capacities of Matrigel Matrix invasion and transendothelial invasion
      than KK-47. These results suggest that the extravasation of KK-47HM4 cells was
      enhanced among the multiple steps of the lung metastasis of bladder cancer. Our
      cDNA microarray analysis identified 67 genes whose expression was up- or
      downregulated in KK-47HM4 cells compared with KK-47 cells. This analysis data
      implied that one possible cause for enhanced extravasation of KK-47HM4 is its
      higher adhesion to extracellular matrix proteins. KK-47HM4 is the first bladder
      cancer subline with enhanced extravasation potential using the in vivo selection
      system. The information provided by our cDNA microarray analysis using KK-47HM4
      will be useful for further investigation into the molecular basis of
      extravasation of cancer cells.

PMID- 23879170
TI  - Ultrasound-mediated vascular endothelial growth factor C (VEGF-C) gene
      microbubble transfection inhibits growth of MCF-7 breast cancer cells.
AB  - We evaluated the effects of ultrasound-mediated microbubble transfection of VEGF
      C siRNA on breast cancer cells in vitro and in vivo. MCF-7 cells were transfected
      with VEGF-C siRNA and the protein and mRNA expression of VEGF-C was tested using
      Western blot and qRT-PCR. Twenty nude mice tumors were established by injecting
      with MCF-7 cells, and were randomized into four groups when palpable tumors
      reached 190 mm3. The length and width of MCF-7 tumors in mice were measured every
      3 days. After 20 days, all mice were killed and the expression of VEGF-C in tumor
      tissue was also detected by Western blot and qRT-PCR. Results showed that VEGF-C
      siRNA effectively suppressed the protein and mRNA expression of VEGF-C in MCF-7
      cells in vitro. VEGF-C siRNA inhibited the growth of human lymphatic endothelial
      cells (LECs) and MCF-7 cells. The volume and weight of MCF-7 tumor in VEGF-C
      siRNA microbubble with irradiation group were reduced with more extent than that
      in other groups in vivo. The present study highlights that VEGF-C siRNA in
      combination with ultrasound-mediated microbubble destruction (UMMD) could be a
      powerful, promising nonviral technology for breast cancer gene therapy.

PMID- 23879172
TI  - FIM-A, a phosphorus-containing sirolimus, inhibits the angiogenesis and
      proliferation of osteosarcomas.
AB  - The mTOR pathway is a central control of cell growth, proliferation, metabolism,
      and survival, and is deregulated in most cancers. Cancer cells are addicted to
      increased activity of mTOR kinase-mediated signaling pathways, leading to
      numerous inhibitors of mTOR signaling in preclinic and clinical trials for cancer
      therapy. Phosphorus-containing sirolimus (FIM-A), which targets mTOR signaling,
      inhibits cancer cell growth in vitro. Here we report that FIM-A reduces the
      angiogenesis and proliferation of osteosarcoma both in vitro and in vivo. In
      cultured osteosarcoma cell lines, FIM-A inhibited cell proliferation and arrested
      cells in the G1 phase of the cell cycle, accompanied with reduction of VEGF and
      HIF-1alpha. With in vivo mouse osteosarcoma xenografts, FIM-A treatment resulted
      in the inhibition of mTORC1 signaling as demonstrated by the decreased
      phosphorylation of p70S6K1 and 4E-BP1. Consistent with this finding, FIM-A
      significantly decreased the average tumor volume, nuclei staining of PCNA, and
      the number of intratumoral microvessels. Our data demonstrated that targeting
      mTORC1 by FIM-A inhibited the growth of osteosarcoma in vitro and in vivo,
      providing the basis for further development of FIM-A as a therapy for
      osteosarcoma patients.

PMID- 23879173
TI  - A phase II study of preoperative chemotherapy with modified FOLFOX6 followed by
      surgery and postoperative chemoradiation in patients with localized gastric
      adenocarcinoma.
AB  - The optimal neoadjuvant and adjuvant treatment for gastric cancer remains
      controversial. We conducted a phase II study using preoperative chemotherapy with
      modified FOLFOX6 followed by surgical resection and postoperative chemoradiation
      in patients with gastric carcinoma. Preoperative chemotherapy (two or three
      cycles) consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid
      (100 mg/m2) followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400
      mg/m2). Surgical resection was planned 4 weeks after the last chemotherapy cycle.
      Patients underwent postsurgical chemoradiation, receiving a total dose of 45 Gy
      and 5-FU continuous infusion (350 mg/m2/day). The primary end points were
      feasibility, overall response rate, and R0 resectability rate after preoperative
      chemotherapy. The secondary end points were tolerability, treatment-associated
      complications, disease-free survival, and overall survival. Nineteen patients
      were enrolled in this study. After neoadjuvant treatment, four patients (21.1%)
      experienced progressive disease, six patients (31.6%) showed partial remission,
      and nine patients (47.3%) showed stable disease. In 15 patients (78.9%) R0
      resectability could be achieved. Eleven of these patients (73.3%) were able to
      undergo postoperative chemoradiation. Notably, eight (72.7%) of these patients
      were disease free and alive at median follow-up of 60 months. Chemotherapy
      associated neutropenia, neutropenic fever, and anastomotic dehiscence were
      observed. The combination of preoperative chemotherapy and postoperative
      chemoradiation is feasible in a significant subset of gastric cancer patients.

PMID- 23879171
TI  - Autocrine-derived epidermal growth factor receptor ligands contribute to
      recruitment of tumor-associated macrophage and growth of basal breast cancer
      cells in vivo.
AB  - Epidermal growth factor receptor (EGFR) expression has been linked to progression
      of basal breast cancers. Many breast cancer cells harbor the EGFR and produce its
      family of ligands, suggesting they may participate in autocrine and paracrine
      signaling with cells of the tumor microenvironment. EGFR ligand expression was
      profiled in the basal breast cancer cell line MDA-231 where AREG, TGF-alpha, and
      HBEGF were the three ligands most highly expressed. Autocrine signaling was
      modulated through silencing or overexpression of these three ligands using
      lentiviral constructs and the impact measured using motility, proliferation, and
      cytokine expression assays. Changes in receptor phosphorylation and receptor
      turnover were examined. Knockdown of AREG or TGF-alpha in vitro resulted in
      decreased motility (p < 0.05) and decreased expression of macrophage
      chemoattractants. Overexpression of TGF-alpha increased motility and
      chemoattractant expression, whereas AREG did not. HBEGF modulation had no effect
      on any cellular behaviors. All the cells with altered ligand production were
      inoculated into female athymic nude mice to form mammary fat pad tumors, followed
      by immunohistochemical analysis for necrosis, angiogenesis, and macrophage
      recruitment. In vivo, knockdown of AREG or TGF-alpha increased survival (p <
      0.001) while decreasing angiogenesis (p < 0.001), tumor growth (p < 0.001), and
      macrophage attraction (p < 0.001). Overexpression of AREG appeared to elicit a
      greater effect than TGF-alpha on mammary fat pad tumor growth by increasing
      angiogenesis (p < 0.001) and macrophage attraction to the tumor (p < 0.01). We
      propose these changes in mammary tumor growth were the result of increased
      recruitment of macrophages to the tumor by cells with altered autocrine EGFR
      signaling. We conclude that AREG and TGF-alpha were somewhat interchangeable in
      their effects on EGFR signaling; however, TGF-alpha had a greater effect in vitro
      and AREG had a greater effect in vivo.

PMID- 23879174
TI  - Photocontrol over cucurbit[8]uril complexes: stoichiometry and supramolecular
      polymers.
AB  - Herein we report the photocontrol of cucurbit[8]uril (CB[8])-mediated
      supramolecular polymerization of azobenzene-containing monomers. The CB[8]
      polymers were characterized both in solution and in the solid state. These host
      guest complexes can be reversibly switched between highly thermostable
      photostationary states. Moreover, a remarkable stabilization of Z-azobenzene was
      achieved by CB[8] complexation, allowing for structural characterization in the
      solid state. 

PMID- 23879175
TI  - Airway hyper-responsiveness in lipopolysaccharide-challenged common marmosets
      (Callithrix jacchus).
AB  - Animal models with a high predictive value for human trials are needed to develop
      novel human-specific therapeutics for respiratory diseases. The aim of the
      present study was to examine lung-function parameters in marmoset monkeys
      (Callithrix jacchus) that can be used to detect pharmacologically or provocation
      induced AHR (airway hyper-responsiveness). Therefore a custom-made lung-function
      device that allows application of defined aerosol doses during measurement was
      developed. It was hypothesized that LPS (lipopolysaccharide)-challenged marmosets
      show AHR compared with non-challenged healthy subjects. Invasive plethysmography
      was performed in 12 anaesthetized orotracheally intubated and spontaneously
      breathing marmosets. Pulmonary data of R(L) (lung resistance), C(dyn) (dynamic
      compliance), EF50 (mid-expiratory flow), P(oes) (oesophageal pressure), MV
      (minute volume), respiratory frequency (f) and V(T) (tidal volume) were
      collected. Measurements were conducted under baseline conditions and under MCh
      (methacholine)-induced bronchoconstriction. The measurement was repeated with the
      same group of animals after induction of an acute lung inflammation by
      intratracheal application of LPS. PDs (provocative doses) of MCh to achieve a
      certain increase in RL were significantly lower after LPS administration. AHR was
      demonstrated in the LPS treated compared with the naive animals. The recorded
      lung-function data provide ground for pre-clinical efficacy and safety testing of
      anti-inflammatory substances in the common marmoset, a new translational NHP (non
      human primate) model for LPS-induced lung inflammation.

PMID- 23879176
TI  - Engineering the esaR promoter for tunable quorum sensing- dependent gene
      expression.
AB  - Quorum sensing (QS) systems enable bacteria to coordinate their behavior as a
      function of local population density and are often used in synthetic systems that
      require cell-cell communication. We have engineered the esaR promoter, P(esaR),
      which is repressed by the QS regulator E(saR). E(saR)-dependent gene expression
      from P(esaR) is induced by 3-oxo-hexanoyl-homoserine lactone (3OC6HSL). Here, we
      report a set of modified P(esaR) promoters that contain a second E(saR) binding
      site. We observed changes in gene expression levels, regulatory range, 3OC6HSL
      sensitivity, and the regulatory role of E(saR) that are dependent on the position
      of the second binding site. Combining the new promoters with endogenous 3OC6HSL
      production led to QS-dependent systems that exhibit a range of expression levels
      and timing. These promoters represent a new set of tools for modulating QS
      dependent gene expression and may be used to tune the regulation of multiple
      genes in response to a single QS signal.

PMID- 23879177
TI  - Antenna effect by organometallic chromophores in bimetallic d-f complexes.
AB  - The nature of the intermetallic bond in a series of complexes of the type [Cp2-TM
      M-Cp2] (where TM = Re and M = Y, La, Lu, Yb, Ac; also TM = Os and M = Th; Cp =
      cyclopentadienyl ligand) have been studied by relativistic two-component density
      functional theory (DFT) calculations. The results obtained in this work show that
      the interaction between the transition metal and lanthanide atoms is mainly ionic
      in all cases, while for the case of actinide atoms this interaction becomes
      significantly more covalent. The effective direction of the electron transfer
      between the Re->Ac or Os->Th centers allows us to propose that the [Cp2ReAcCp2]
      and [Cp2OsThCp2] complexes are ideal candidates for near-infrared (NIR)
      technologies since their absorption spectra show some transitions over 600 nm. We
      also observed a shifting of the absorption spectrum of around 100 nm of the
      [Cp2Re] fragment when is compared against the absorption spectrum of the entire
      complex. This behavior allows us to argue that the [Cp2Re] fragment is a good
      antenna chromophore due to the possibility of charge transfer transitions from
      this fragment to the f shell in lanthanide or actinide elements studied here. 

PMID- 23879179
TI  - The NACCT abstract review process.

PMID- 23879178
TI  - Improving the management of people with a family history of breast cancer in
      primary care: before and after study of audit-based education.
AB  - BACKGROUND: In England, guidance from National Institute for Clinical Excellence
      (NICE) states women with a family history of breast cancer presenting to primary
      care should be reassured or referred.We reviewed the evidence for interventions
      that might be applied in primary care and conducted an audit of whether low risk
      women are correctly advised and flagged. METHODS: We conducted a literature
      review to identify modifiable risk factors. We extracted routinely collected data
      from the computerised medical record systems of 6 general practices (population
      approximately 30,000); of the variables identified in the guidance. We
      implemented a quality improvement (QI) intervention called audit-based education
      (ABE) comparing participant practices with guidelines and each other before and
      after; we report odds ratios (OR) of any change in data recording. RESULTS: The
      review revealed evidence for advising on: diet, weight control, physical
      exercise, and alcohol. The proportion of patients with recordings of family
      history of: disease, neoplasms, and breast cancer were: 39.3%, 5.1% and 1.3%
      respectively. There was no significant change in the recording of family history
      of disease or cancer; OR 1.02 (95% CI 0.98-1.06); and 1.08 (95% CI 0.99-1.17)
      respectively. Recording of alcohol consumption and smoking both increased
      significantly; OR 1.36 (95% CI 1.30-1.43); and 1.42 (95% CI 1.27-1.60)
      respectively. Recording lifestyle advice fell; OR 0.84 (95% CI 0.81-0.88).
      CONCLUSIONS: The study informs about current data recording and willingness to
      engage in ABE. Recording of risk factors improved after the intervention. Further
      QI is needed to achieve adherence to current guidance.

PMID- 23879180
TI  - Hump-nosed pit viper (Hypnale hypnale) envenoming causes mild coagulopathy with
      incomplete clotting factor consumption.
AB  - CONTEXT: Limited information exists on the coagulopathy caused by hump-nosed pit
      viper (Hypnale hypnale) envenoming. OBJECTIVES: This study aimed to characterise
      the coagulopathy in hump-nosed pit viper bites by measuring laboratory clotting
      times and factor studies. MATERIALS AND METHODS: Cases of hump-nosed pit viper
      envenoming were included from a prospective cohort study of Sri Lankan snake-bite
      patients. Patient age, sex, snake identification, time of bite and clinical
      effects were recorded. Patients did not receive anti-venom because no specific
      anti-venom to hump-nosed vipers exists. All patients received supportive care and
      serial 20-min whole blood clotting tests (WBCT20). The prothrombin time (PT),
      international normalised ratio (INR), activated partial thromboplastin time
      (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, von Willebrand factor
      (vWF) antigen and D-Dimer concentrations were measured. The median of highest or
      lowest test result for each patient was reported with interquartile range (IQR).
      Results. There were 80 hump-nosed pit viper bites, median age was 37 years (IQR:
      26-51 years) and 48 were male. The WBCT20 was positive in one patient. The median
      highest INR was 1.9 (1.5-2.2; Range: 1.3 to > 12) and median highest aPTT was 54
      s (46-72 s; Range: 35-170 s). There was low fibrinogen [median: 1.3 g/L;1, -1.8
      g/L; Range: < 0.2-2.9], low factor VIII levels [median: 23%; 16-37%] and low
      factor V levels [median: 43%; 23-74%]. D-Dimer concentrations [median: 3.4 mg/L;
      2-7.4 mg/L] were slightly elevated. Factors II, VII and X and vWF antigen
      concentrations were normal. DISCUSSION AND CONCLUSIONS: Hump-nosed pit viper
      bites result in a mild coagulopathy which is usually not detected by a WBCT20. It
      is characterised by mild elevation of INR, low fibrinogen and Factors V and VIII
      which may be consistent with the venom containing a thrombin-like enzyme.

PMID- 23879181
TI  - An analysis of energy-drink toxicity in the National Poison Data System.
AB  - CONTEXT: Small studies have associated energy drinks-beverages that typically
      contain high concentrations of caffeine and other stimulants-with serious adverse
      health events. OBJECTIVE: To assess the incidence and outcomes of toxic exposures
      to caffeine-containing energy drinks, including caffeinated alcoholic energy
      drinks, and to evaluate the effect of regulatory actions and educational
      initiatives on the rates of energy drink exposures. METHODS: We analyzed all
      unique cases of energy drink exposures reported to the US National Poison Data
      System (NPDS) between October 1, 2010 and September 30, 2011. We analyzed only
      exposures to caffeine-containing energy drinks consumed as a single product
      ingestion and categorized them as caffeine-containing non-alcoholic, alcoholic,
      or "unknown" for those with unknown formulations. Non-alcoholic energy drinks
      were further classified as those containing caffeine from a single source and
      those containing multiple stimulant additives, such as guarana or yerba mate. The
      data were analyzed for the demographics and outcomes of exposures (unknown data
      were not included in the denominator for percentages). The rates of change of
      energy drink-related calls to poison centers were analyzed before and after major
      regulatory events. RESULTS: Of 2.3 million calls to the NPDS, 4854 (0.2%) were
      energy drink-related. The 3192 (65.8%) cases involving energy drinks with unknown
      additives were excluded. Of 1480 non-alcoholic energy drink cases, 50.7% were
      children < 6 years old; 76.7% were unintentional; and 60.8% were males. The
      incidence of moderate to major adverse effects of energy drink-related toxicity
      was 15.2% and 39.3% for non-alcoholic and alcoholic energy drinks, respectively.
      Major adverse effects consisted of three cases of seizure, two of non-ventricular
      dysrhythmia, one ventricular dysrhythmia, and one tachypnea. Of the 182
      caffeinated alcoholic energy drink cases, 68.2% were < 20 years old; 76.7% were
      referred to a health care facility. Educational and legislative initiatives to
      enhance understanding of the health consequences of energy drink consumption were
      significantly associated with a decreased rate of energy drink-related cases (p =
      0.036). CONCLUSIONS: About half the cases of energy drink-related toxicity
      involved unintentional exposures by children < 6 years old. Educational campaigns
      and legal restrictions on the sale of energy drinks were associated with
      decreasing calls to poison centers for energy drink toxicity and are encouraged.

PMID- 23879183
TI  - Multi-species biofilms defined from drinking water microorganisms provide
      increased protection against chlorine disinfection.
AB  - A model biofilm, formed of multiple species from environmental drinking water,
      including opportunistic pathogens, was created to explore the tolerance of multi
      species biofilms to chlorine levels typical of water-distribution systems. All
      species, when grown planktonically, were killed by concentrations of chlorine
      within the World Health Organization guidelines (0.2-5.0 mg l(-1)). Higher
      concentrations (1.6-40-fold) of chlorine were required to eradicate biofilm
      populations of these strains, ~70% of biofilms tested were not eradicated by 5.0
      mg l(-1) chlorine. Pathogenic bacteria within the model multi-species biofilms
      had an even more substantial increase in chlorine tolerance; on average ~700-1100
      mg l(-1) chlorine was required to eliminate pathogens from the biofilm, 50-300
      fold higher than for biofilms comprising single species. Confocal laser scanning
      microscopy of biofilms showed distinct 3D structures and multiple cell
      morphologies and arrangements. Overall, this study showed a substantial increase
      in the chlorine tolerance of individual species with co-colonization in a multi
      species biofilm that was far beyond that expected as a result of biofilm growth
      on its own.

PMID- 23879184
TI  - Anthropometric, body composition and somatotype characteristics of elite female
      volleyball players from the highest Spanish league.
AB  - This study aimed to describe morphological characteristics of elite female
      volleyball players from the highest Spanish league, with special focus on
      differences by performance level and playing positions. Nearly all female players
      playing in the highest Spanish volleyball league during season 2003/2004
      participated in this study (N=148 elite players, 92% of the total).
      Anthropometric, body composition and somatotype parameters according to
      performance and playing positions were analysed. The players' characteristics
      were as follows; body mass 72.3 +/- 8.4 kg; stature 179.8 +/- 7.1 cm; body fat
      24.0 +/- 3.1% and skeletal muscle mass 27.3 +/- 2.9 kg. Mean somatotype was 3.1
      +/- 0.7; 3.4 +/- 0.9; 3.1 +/- 0.9 characterised as central with a tendency to
      balanced mesomorph. Top level players (whose teams were better classified in the
      team performance ranking) were taller, had higher skeletal muscle mass and
      ectomorphy, and had a lower level of adiposity markers, compared with lower level
      players. Players selected for their respective National teams (individual
      performance) were taller, heavier, had higher muscle mass and lower endomorphy
      than non-selected players. Differences according to playing positions were found.
      This study provides a complete set of reference data on anthropometry, body
      composition and somatotype of elite female volleyball players. Morphological
      differences have been identified according to performance level and playing
      position.

PMID- 23879185
TI  - Proteomic analysis of leptomeningeal amyloid fibril extracts of cerebral amyloid
      angiopathy (CAA) patients with or without corticosteroid therapy.

PMID- 23879189
TI  - Phototactic behavior of the Armand pine bark weevil, Pissodes punctatus.
AB  - The Armand pine bark weevil, Pissodes punctatus Langor et Zhang (Coleoptera:
      Curculionidae) is a destructive bark weevil on the Armand pine, Pinus armandii
      Franch (Pinales: Pinaceae), an important timbering tree in southern China. This
      study examined the phototactic behavior ieP. punctatus through observation of
      behavioral characteristics, response to nine monochromatic lights (ranging from
      340 nm to 689 nm with about 40-nm step), and response to five intensities
      (ranging from 1 lux to 200 lux) of the most attractive light. The results
      demonstrated that P. punctatus was most active in the day, and kept still at
      night (or in a dark room). P. punctatus could be attracted to eight of nine
      monochromatic lights, the exception being red light (649 nm), which implied broad
      sensitivity to the spectrum of light. P. punctatus was most sensitive to violet
      (415 nm), ultraviolet (340 nm), and green (504 nm) light, suggesting there might
      be at least three types of photoreceptors in the compound eyes of this weevil.
      Furthermore, low intensities elicited an increased phototactic response, and high
      intensities a decreased phototactic response, under both violet and UV light.
      Thus, P. punctatus were found to be phototactic insects, and the phototactic
      behavior of P. punctatus is both a color and intensity preference. The
      information provided here provides a basis for the improvement of trapping
      devices for detection and survey of P. punctatus, as well as a basis for the
      development of alternate control strategies for this important pest of Armand
      pine and other pine trees.

PMID- 23879188
TI  - Split of chiral degeneracy in mechanical and structural properties of
      oligopeptide-polysaccharide biomaterials.
AB  - Enantiomeric biomaterials which are mirror images of each other are characterized
      by chiral degeneracy--identical structural characteristics and bulk material
      properties. The addition of another chiral component, D-polysaccharide, has been
      shown to split such degeneracy and result in two distinct biomaterials. Dynamic
      oscillatory rheometry and small-angle X-ray scattering demonstrate that the
      natural biochirality combination of L-peptides and D-polysaccharides assembles
      faster, has higher elastic moduli (G'), and is structurally more beneficial as
      opposed to the alternative D-peptide and D-polysaccharide combination. Chemical
      modifications of the OH-groups in alpha-D-glucose units in D-polysaccharides
      weaken such splitting of chiral degeneracy. These findings form a basis to design
      novel biomaterials and provide additional insight on why proteins and
      polysaccharides have oppoiste chirality in the biological world.

PMID- 23879190
TI  - Obesity and atrial fibrillation.
AB  - Atrial fibrillation (AF) is an increasing public health problem, often described
      as the epidemic of the new millennium. The rising health economic impact of AF,
      its association with poor quality of life and independent probability of
      increased mortality, has recently been highlighted. Although population ageing is
      regarded as an important contributor to this epidemic, obesity and its associated
      cardiometabolic comorbidities may represent the principal driving factor behind
      the current and projected AF epidemic. Obesity-related risk factors, such as
      hypertension, vascular disease, obstructive sleep apnea and pericardial fat, are
      thought to result in atrial electro-structural dysfunction. In addition, insulin
      resistance, its associated abnormalities in nutrient utilization and intermediary
      metabolic by-products are associated with structural and functional
      abnormalities, ultimately promoting AF. Recent elucidation of molecular pathways,
      including those responsible for atrial fibrosis, have provided mechanistic
      insights and the potential for targeted pharmacotherapy. In this article, we
      review the evidence for an obesity-related atrial electromechanical dysfunction,
      the mechanisms behind this and its impact on AF therapeutic outcomes. In light of
      the recently described mechanisms, we illustrate proposed management approaches
      and avenues for further investigations. 

PMID- 23879191
TI  - Global midwifery education collaborations: translating knowledge into ethical
      action.

PMID- 23879192
TI  - The prognostic role of the new entity butterfly-like facial rash and cutaneous
      findings in patients with crimean congo haemorrhagic fever.
AB  - BACKGROUND: Crimean Congo Haemorrhagic Fever (CCHF) is a deadly fever caused by
      Nairovirus (family Bunyaviridae). It is an important public health problem in
      hyperendemic regions with a high mortality rate. There have been many studies on
      cutaneous findings in other viral infections, however, our knowledge is limited
      regarding CCHF. The aim of this study was to evaluate the cutaneous
      manifestations of CCHF and their relationship with mortality. METHODS: Patients
      who were diagnosed CCHF between April 1 and September 1, 2011 were enrolled in
      this study. Dermatologic examination and laboratory analysis were obtained during
      hospitalization. RESULTS: A new entity that is first reported in this study as a
      butterfly-like facial rash was recognized in 76 patients (42.9%). It was not
      correlated with mortality but could coexist with other dermatological signs of
      CCHF. The major outcome was the increased mortality rate with other cutaneous
      findings (especially ecchymosis, purpura and petechia) (P < 0.01). While 12
      deceased individuals had one or more skin findings, only one patient died without
      any cutaneous manifestations. Mortality rate was higher in patients with purpura
      than the patients with pethesia. The statistically significant correlation was
      observed between cutaneous manifestations and elevation of aspartate
      aminotransferase (AST) levels (P = 0.009). Platelet levels were lower in patients
      with cutaneous involvement (P < 0.01). No statistically significant relationship
      was found between cutaneous findings and alanine aminotransferase (ALT), white
      blood cell (WBC), Haemoglobin (Hb), creatinine kinase (CK) and lactate
      dehydrogenase (LDH) levels. LIMITATIONS: Histopathologic examination of facial
      rash could not be done because of haemostatic failure. CONCLUSION: The results of
      this study confirm that cutaneous findings can be a clue regarding the prognosis
      of the patients with CCHF. Physicians should be aware that CCHF may present with
      a butterfly-like rash on the face.

PMID- 23879193
TI  - Integrative invasion science: model systems, multi-site studies, focused meta
      analysis and invasion syndromes.
AB  - Invasion science is a very active subdiscipline of ecology. However, some
      scientists contend that theoretical integration has been limited and that
      predictive power remains weak. This paper, focusing on plants, proposes a new
      multi-pronged research strategy that builds on recent advances in invasion
      science. More intensive studies on particular model organisms and ecosystems are
      needed to improve our understanding of the full suite of interacting factors that
      influence invasions ('model system research'). At the same time, comparative
      studies across many study systems are essential for unravelling the context
      dependencies of insights that emerge from particular studies ('multi-site
      studies'); and quantitative synthesis based on large datasets should be
      constrained to well-defined theoretical domains ('focused meta-analysis'). We
      also suggest ways for better integration of information about species biology and
      ecosystem characteristics ('invasion syndromes'). We expect that a resulting
      theory of invasions will need to be conceived as a somewhat heterogeneous
      conglomerate of elements of varying generality and predictive power: laws that
      apply to well-specified domains, general concepts and theoretical frameworks that
      can guide thinking in research and management, and in-depth knowledge about the
      drivers of particular invasions.

PMID- 23879194
TI  - Psoriasis and the Framingham risk score in a Danish hospital cohort.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease, which is associated
      with an increased risk of cardiovascular morbidity and mortality. Our aim was to
      compare the Framingham risk score, a method to estimate coronary heart disease
      and prevalences of cardiovascular risk factors in patients with psoriasis and the
      general population. METHODS: We retrospectively studied a hospital cohort and
      used a cross-sectional random sample from the general population as controls.
      RESULTS: A total of 185 patients with psoriasis aged 10-86 years were referred to
      our department during 2009-2011. Median psoriasis area and severity index score
      was 5.8 (range 0.0-39.8), and 10% of the patients received systemic antipsoriatic
      treatment. Body mass index (26.2 vs. 25.2 kg/m(2) , P = 0.005), waist
      circumference (96.0 vs. 88.0 cm, P < 0.001), and prevalence of
      hypercholesterolemia (15.1 vs. 14.5, P = 0.009) were significantly higher in
      patients with psoriasis. We found no significant differences in Framingham risk
      scores between the groups. CONCLUSIONS: Patients from the hospital cohort had a
      higher prevalence of certain cardiovascular risk factors compared to individuals
      without psoriasis from the general population. However, the Framingham risk score
      did not demonstrate an excess risk of coronary heart disease in patients with
      psoriasis compared to controls.

PMID- 23879195
TI  - Clinical profile of primary biliary cirrhosis with features of autoimmune
      hepatitis: Importance of corticosteroid therapy.
AB  - AIM: The aim of this study was to elucidate the clinical and histological
      features, response to corticosteroid therapy and long-term outcome of primary
      biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH). METHODS:
      Among 280 PBC patients under ursodeoxycholic acid administration, we identified
      28 patients with AIH features fulfilling the following criteria: sustained high
      levels of serum aminotransferases and high immunoglobulin G levels with
      positivity for antinuclear antibodies or anti-smooth muscle antibodies (ASMA)
      and/or histological features of moderate to severe interface hepatitis or
      moderate to severe lobular hepatitis. We analyzed PBC patients with AIH features,
      focusing mainly on therapeutic responses to corticosteroids. RESULTS: Patients
      with PBC with AIH features included 26 women (93%). Their median age was 55
      years, and the median follow-up period was 7.5 years. Eight of these 28 patients
      were not actually treated with corticosteroids due to medical conditions. Among
      the 20 patients receiving corticosteroid therapy, 15 were responders and five
      were non-responders. A high alkaline phosphatase (ALP) level, negativity for ASMA
      and positivity for gp210 were identified as risk factors for lack of a response
      to corticosteroid therapy. Among 28 PBC patients with AIH features, the
      responders to corticosteroids had an excellent prognosis, while those who could
      not be treated with corticosteroids and non-responders to corticosteroids had a
      poor outcome. CONCLUSION: Patients with PBC with AIH features benefit from
      corticosteroid therapy. Features of PBC such as high ALP level, negativity for
      ASMA and positivity for gp210 appear to predict a poor response to
      corticosteroids.

PMID- 23879196
TI  - High-throughput investigation of catalysts for JP-8 fuel cracking to liquefied
      petroleum gas.
AB  - Portable power technologies for military applications necessitate the production
      of fuels similar to LPG from existing feedstocks. Catalytic cracking of military
      jet fuel to form a mixture of C2-C4 hydrocarbons was investigated using high
      throughput experimentation. Cracking experiments were performed in a gas-phase,
      16-sample high-throughput reactor. Zeolite ZSM-5 catalysts with low Si/Al ratios
      (<=25) demonstrated the highest production of C2-C4 hydrocarbons at moderate
      reaction temperatures (623-823 K). ZSM-5 catalysts were optimized for JP-8
      cracking activity to LPG through varying reaction temperature and framework Si/Al
      ratio. The reducing atmosphere required during catalytic cracking resulted in
      coking of the catalyst and a commensurate decrease in conversion rate. Rare earth
      metal promoters for ZSM-5 catalysts were screened to reduce coking deactivation
      rates, while noble metal promoters reduced onset temperatures for coke burnoff
      regeneration.

PMID- 23879197
TI  - Structural properties of non-traditional drug targets present new challenges for
      virtual screening.
AB  - Traditional drug targets have historically included signaling proteins that
      respond to small molecules and enzymes that use small molecules as substrates.
      Increasing attention is now being directed toward other types of protein targets,
      in particular those that exert their function by interacting with nucleic acids
      or other proteins rather than small-molecule ligands. Here, we systematically
      compare existing examples of inhibitors of protein-protein interactions to
      inhibitors of traditional drug targets. While both sets of inhibitors bind with
      similar potency, we find that the inhibitors of protein-protein interactions
      typically bury a smaller fraction of their surface area upon binding to their
      protein targets. The fact that an average atom is less buried suggests that more
      atoms are needed to achieve a given potency, explaining the observation that
      ligand efficiency is typically poor for inhibitors of protein-protein
      interactions. We then carried out a series of docking experiments and found a
      further consequence of these relatively exposed binding modes is that structure
      based virtual screening may be more difficult: such binding modes do not provide
      sufficient clues to pick out active compounds from decoy compounds. Collectively,
      these results suggest that the challenges associated with such non-traditional
      drug targets may not lie with identifying compounds that potently bind to the
      target protein surface, but rather with identifying compounds that bind in a
      sufficiently buried manner to achieve good ligand efficiency and, thus, good oral
      bioavailability. While the number of available crystal structures of distinct
      protein interaction sites bound to small-molecule inhibitors is relatively small
      at present (only 21 such complexes were included in this study), these are
      sufficient to draw conclusions based on the current state of the field; as
      additional data accumulate it will be exciting to refine the viewpoint presented
      here. Even with this limited perspective however, we anticipate that these
      insights, together with new methods for exploring protein conformational
      fluctuations, may prove useful for identifying the "low-hanging fruit" among non
      traditional targets for therapeutic intervention. 

PMID- 23879198
TI  - The effect of the implementation of therapeutic hypothermia on fluid balance and
      incidence of hyponatremia in neonates with moderate or severe hypoxic-ischaemic
      encephalopathy.
AB  - AIM: To investigate the effect of the therapeutic hypothermia (TH), used in
      infants with moderate or severe hypoxic-ischaemic encephalopathy (HIE), on fluid
      balance and incidence of hyponatremia. METHODS: Retrospective cohort study of
      moderate and severe HIE infants before (pre) and after (post) TH implementation.
      Daily fluid and electrolytes intake/output were collected from the medical
      records of each patient from day 1 to day 4 of life. Hyponatremia was defined as
      sodium <130 mEq/L. RESULTS: A total of 67 infants were studied: pre-TH = 29 and
      post-TH = 38. Infants in the post-TH group had greater weight gain [140 g (62,
      227) vs. 10 g (-100, 105) p < 0.001] and lower serum sodium (130.9 +/- 4.5 mmol/L
      vs. 133.4 +/- 5.7, p = 0.008). The incidence of hyponatremia increased from 48 to
      76% (p = 0.02). CONCLUSION: In our centre, the implementation of TH was followed
      by an increased fluid retention and higher incidence of hyponatremia. Centres
      adopting TH should have clear guidelines for fluid and electrolyte management.

PMID- 23879199
TI  - Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non
      melanoma skin cancers are common in patients with Philadelphia-negative
      myeloproliferative neoplasms treated with hydroxyurea.
AB  - Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive
      non-melanoma skin cancers and other hydroxyurea complications have been reported
      in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence
      and clinical consequences have not been defined in a large cohort of patients. We
      conducted a retrospective analysis of 188 consecutive patients with MPNs
      specifically addressing the incidence of these complications. Cyclical
      thrombocytosis was documented in 29 patients (15%), the majority of whom were
      receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of
      the 84 screened patients (20%), but was not associated with any major bleeding
      complications. Non-melanoma skin cancers were reported in 51 patients (27%).
      Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received
      hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major
      thrombotic events, with the majority of these occurring prior to or within 3
      months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand
      syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related
      complications are not infrequent in MPNs and have important clinical consequences
      for management. 

PMID- 23879200
TI  - Mimic of manganese superoxide dismutase induces apoptosis in human acute myeloid
      leukemia cells.
AB  - Abstract Increasing manganese superoxide dismutase (MnSOD) expression can
      suppress the malignant phenotype in various cancer cell lines and suppress tumor
      formation in xenograft and transgenic mouse models. A mimic of manganese
      superoxide dismutase (MnSODm), synthesized by a chemical method, has been shown
      to possess antitumor properties. However, the anticancer activity of MnSODm in
      acute myeloid leukemia (AML) is still obscure. In this study, we investigated the
      effects of MnSODm on the apoptosis of human leukemia HL-60 cells. Results showed
      that MnSODm significantly reduced the proliferation of HL-60 cells in a
      concentration- and time-dependent manner. By flow cytometric analysis, we found
      that MnSODm treatment resulted in increased apoptosis in HL-60 cells. Further
      analysis demonstrated involvement of activation of the caspase cascade, cleavage
      of poly(ADP-ribose) polymerase (PARP) and release of cytochrome c in MnSODm
      induced apoptosis. The results also showed that the expression of anti-apoptotic
      Bcl-2 and Bid were dose-dependently decreased, whereas the expression of pro
      apoptotic Bax protein was increased. Thus, MnSODm induced apoptosis in HL-60
      cells via mitochondria-mediated, caspase-dependent pathways. MnSODm inhibition of
      Akt phosphorylation may contribute to MnSODm-mediated acute myeloid leukemia cell
      growth inhibition and apoptosis induction. 

PMID- 23879201
TI  - Recent improvement in survival of patients with multiple myeloma: variation by
      ethnicity.
AB  - Abstract Survival for patients with multiple myeloma has increased during the
      first decade of the 21st century. However, it is unknown whether the improvements
      in survival have extended equally in all ethnic groups. Using data from the
      United States Surveillance, Epidemiology and End Results Program, we assessed
      trends in survival and disease-related mortality for patients with myeloma by
      ethnic group, including non-Hispanic whites (nHw), African-Americans (AA),
      Hispanics and people of Asian and Pacific Islander descent (API) from 1998-2001
      to 2006-2009. Overall, age adjusted 5-year relative survival increased, from
      35.6% in 1998-2001 to 44% in 2006-2009. The greatest improvements were observed
      for patients aged 15-49, for whom survival increased by + 16.8% units for nHw and
      + 14.4% units for AA, whereas improvement was less pronounced and not
      statistically significant in Hispanics and API. Excess mortality hazard ratios
      were 1.20 (95% confidence interval [CI]: 1.09-1.33) for AA and 1.25 (95% CI: 1.11
      1.41) for Hispanics compared to nHw in 2006-2009. Although survival increased
      greatly for nHw with myeloma between 1998-2001 and 2006-2009, smaller increases
      were observed for people of other ethnic groups. Persistent excess mortality was
      seen for AA and Hispanic patients with myeloma. Ethnic inequalities persisted or
      even increased from earlier periods to 2006-2009. The results suggest that ethnic
      minorities may not have benefited from newer treatments to the same extent as nHw
      patients have. 

PMID- 23879202
TI  - Clinical value of magnetic resonance imaging and other baseline testing for
      conjunctival mucosa-associated lymphoid tissue lymphoma.
AB  - Abstract The objective of this study was to assess the value of magnetic
      resonance imaging (MRI) of the orbit for conjunctival mucosa-associated lymphoid
      tissue (MALT) lymphoma. The yield of other staging tests at baseline were also
      evaluated. Twenty-one consecutive patients treated for conjunctival MALT lymphoma
      were retrospectively studied. Lymphoma was staged according to both the Ann Arbor
      system and the seventh edition of the AJCC [American Joint Committee on Cancer]
      cancer staging manual. Findings on MRI of the orbit, whole-body positron emission
      tomography/computed tomography (PET/CT), CT of the chest/abdomen/pelvis, bone
      marrow (BM) biopsy and gastrointestinal (GI) endoscopy were recorded. Seventeen
      patients had orbital MRI. Fourteen of 17 patients (82%) with obvious conjunctival
      MALT lymphoma on clinical examination had a negative MRI scan. Only three
      patients had subtle conjunctival enhancement on orbital MRI. Ann Arbor stage at
      presentation was as follows: stage IE (15 patients), stage IIE (two patients) and
      stage IV (four patients). Eighteen of 21 patients had total-body PET/CT; four
      patients (22%) had hypermetabolic activity evident on PET scan. All 21 patients
      had bilateral BM biopsies. Fifteen of 21 patients (71%) had GI endoscopy. None of
      the patients had a positive BM biopsy or findings on GI endoscopy. Our data
      suggest that orbital MRI has a very low yield for identification of conjunctival
      MALT lymphoma. Clinical examination is critical in diagnosing and assessing
      treatment response in conjunctival MALT lymphoma. The yield for GI endoscopy and
      BM biopsy may also be low in staging of conjunctival MALT lymphoma. 

PMID- 23879203
TI  - Central nervous system venulitis presenting as migraine.
AB  - OBJECTIVE: To describe a case of pediatric central nervous system (CNS)
      venulitis. BACKGROUND: Primary angiitis of the CNS is a rare but increasingly
      well-recognized cause of morbidity in children. It primarily involves the
      arteries and arterioles of the CNS, with only 1 published case of a pediatric
      patient found to have isolated CNS venulitis on brain biopsy. CASE REPORT: A 17
      year-old female with a 4-year history of migraines presented with increasingly
      frequent migraines and right-sided hemiplegia. Infectious, hematologic, and
      rheumatologic work-ups were negative. Brain magnetic resonance imaging showed
      multiple rim-enhancing lesions consistent with calcifications affecting the deep
      left white matter. On brain biopsy, there was evidence of an inflammatory process
      involving small veins and venules. The patient displayed clinical improvement
      with a course of high-dose steroids and 6 monthly cyclophosphamide infusions
      followed by maintenance therapy with mycophenolate mofetil. DISCUSSION: We
      describe a case of pediatric CNS venulitis presenting with migraine.

PMID- 23879205
TI  - Induced pluripotent stem cells from friedreich ataxia patients fail to upregulate
      frataxin during in vitro differentiation to peripheral sensory neurons.
AB  - The value of human disease models, which are based on induced pluripotent stem
      cells (iPSCs), depends on the capacity to generate specifically those cell types
      affected by pathology. We describe a new iPSC-based model of Friedreich ataxia
      (FRDA), an autosomal recessive neurodegenerative disorder with an intronic GAA
      repeat expansion in the frataxin gene. As the peripheral sensory neurons are
      particularly susceptible to neurodegeneration in FRDA, we applied a development
      based differentiation protocol to generate specifically these cells. FRDA and
      control iPSC lines were efficiently differentiated toward neural crest
      progenitors and peripheral sensory neurons. The progress of the cell lines
      through discrete steps of in vitro differentiation was closely monitored by
      expression levels of key markers for peripheral neural development. Since it had
      been suggested that FRDA pathology might start early during ontogenesis, we
      investigated frataxin expression in our development-related model. A pronounced
      frataxin deficit was found in FRDA iPSCs and neural crest cells compared to
      controls. Whereas we identified an upregulation of frataxin expression during
      sensory specification for control cells, this increase was not observed for FRDA
      peripheral sensory neurons. This early failure, aggravating frataxin deficiency
      in a specifically vulnerable human cell population, indicates a developmental
      component in FRDA. 

PMID- 23879204
TI  - Restriction to large-scale gene flow vs. regional panmixia among cold seep
      Escarpia spp. (Polychaeta, Siboglinidae).
AB  - The history of colonization and dispersal in fauna distributed among deep-sea
      chemosynthetic ecosystems remains enigmatic and poorly understood because of an
      inability to mark and track individuals. A combination of molecular,
      morphological and environmental data improves understanding of spatial and
      temporal scales at which panmixia, disruption of gene flow or even speciation may
      occur. Vestimentiferan tubeworms of the genus Escarpia are important components
      of deep -sea cold seep ecosystems, as they provide long-term habitat for many
      other taxa. Three species of Escarpia, Escarpia spicata [Gulf of California
      (GoC)], Escarpia laminata [Gulf of Mexico (GoM)] and Escarpia southwardae (West
      African Cold Seeps), have been described based on morphology, but are not
      discriminated through the use of mitochondrial markers (cytochrome oxidase
      subunit 1; large ribosomal subunit rDNA, 16S; cytochrome b). Here, we also
      sequenced the exon-primed intron-crossing Haemoglobin subunit B2 intron and
      genotyped 28 microsatellites to (i) determine the level of genetic
      differentiation, if any, among the three geographically separated entities and
      (ii) identify possible population structure at the regional scale within the GoM
      and West Africa. Results at the global scale support the occurrence of three
      genetically distinct groups. At the regional scale among eight sampling sites of
      E. laminata (n = 129) and among three sampling sites of E. southwardae (n = 80),
      no population structure was detected. These findings suggest that despite the
      patchiness and isolation of seep habitats, connectivity is high on regional
      scales. 

PMID- 23879206
TI  - Reference range of thyroid hormones in very low birth weight infants at the time
      of discharge.
AB  - AIM: There is little information regarding the reference range for thyroid
      hormones in preterm babies, especially those with very low birth weight (VLBW) of
      less than 1500 g. The objective of our study was to evaluate the relationship
      between thyroid hormone levels and postmenstrual age in a cohort of stable VLBW
      infants. METHOD: An observational cohort study of VLBW infants preparing for
      discharge from a high-dependency nursery in Singapore. The infants' free
      thyroxine (fT4) and thyrotropin (TSH) levels were assayed just before discharge
      and correlated with postmenstrual age, calculated as the sum of the duration of
      gestation at birth and chronological age in weeks. RESULTS: fT4 and TSH levels
      were sampled in 129 ex-VLBW babies at a mean postmenstrual age of 38.5 (+/-4.6)
      weeks. The babies were born at a mean+/-SD gestation of 28.9+/-2.4 weeks (median
      29.0 weeks, range 24.0-34.5 weeks) with mean+/-SD birth weight of 1081+/-268 g
      (median 1090 g, range 490-1490 g). Linear regression analysis revealed negative
      and fair correlation between fT4 and postmenstrual age (r=-0.302). The mean+/-SD
      fT4 level was 16.8+/-3.2 pmol/L (median 16.8 pmol/L, range 8.5-28.9 pmol/L).
      However, there was only a very weak negative correlation between TSH levels and
      postmenstrual age, both with (r=-0.116) or without logarithmic transformation.
      The mean+/-SD TSH was 4.56+/-2.50 mIU/L (median 4.42 mIU/L, range 1.0-13.5
      mIU/L). CONCLUSION: Our study shows a fair and inverse correlation of fT4 with
      postmenstrual age in a large cohort of growing ex-VLBW infants, in keeping with
      maturation of the hypothalamic-pituitary-thyroid axis. It suggests that fT4
      levels in growing infants are best compared to postmenstrual age-specific norms
      instead of a single reference interval.

PMID- 23879207
TI  - Surface-driven sodium ion energy storage in nanocellular carbon foams.
AB  - Sodium ion (Na(+)) batteries have attracted increased attention for energy
      storage due to the natural abundance of sodium, but their development is hindered
      by poor intercalation property of Na(+) in electrodes. This paper reports a
      detailed study of high capacity, high rate sodium ion energy storage in
      functionalized high-surface-area nanocellular carbon foams (NCCF). The energy
      storage mechanism is surface-driven reactions between Na(+) and oxygen-containing
      functional groups on the surface of NCCF. The surface reaction, rather than a
      Na(+) bulk intercalation reaction, leads to high rate performance and cycling
      stability due to the enhanced reaction kinetics and the absence of electrode
      structure change. The NCCF makes more surface area and surface functional groups
      available for the Na(+) reaction. It delivers 152 mAh/g capacity at the rate of
      0.1 A/g and a capacity retention of 90% for over 1600 cycles. 

PMID- 23879208
TI  - Evaluation of effectiveness of cryotherapy on the treatment of cutaneous Kaposi's
      sarcoma.
AB  - OBJECTIVE: Kaposi's sarcoma (KS) is a vascular tumor that affects the skin and
      other organs. Several therapeutic options are available, but the optimal therapy
      is unclear. The aim of this study was to determine the effectiveness and safety
      of cryotherapy in the treatment of KS. MATERIALS AND METHODS: Thirty patients
      were evaluated. Cryotherapy was applied using liquid nitrogen. Each treatment
      consisted of two freeze-thaw cycles, with freezing times ranging from 15 to 40
      seconds per cycle. RESULTS: One hundred twenty-five lesions were treated in an
      average of 3.2 sessions. Complete response was observed in 19 (63%) of the 30
      patients after cryotherapy treatment with no recurrence. The subjects tolerated
      cryotherapy well. Blistering occurred frequently, but local pain was limited.
      There were no secondary infections. CONCLUSION: Liquid nitrogen cryotherapy is
      safe and cost-efficient and can be readily adopted as an effective primary
      therapy for cutaneous KS lesions that respond slowly or show incomplete cosmetic
      improvement after systemic therapies.

PMID- 23879209
TI  - Quality of life in men with involuntary childlessness: long-term follow-up.
AB  - We conducted a longitudinal cohort study on the quality of life of infertile male
      patients measured at baseline and after 5 years with a specific quality of life
      instrument for male patients who are involuntarily childless. It was distributed
      to patients who were seen at the andrology and gynaecology clinics for
      infertility diagnoses and treatment. At baseline (T1), 275 patients took part in
      the study. A subset of these patients (N = 133) had released two semen samples,
      and the results of the semen analysis had been communicated to them before they
      received the questionnaire. Semen quality of this subset was assessed according
      to WHO recommendations. After 5 years (T2), the questionnaires were mailed again
      and were sent back by N = 101 patients. No significant quality of life difference
      was found between the semen quality groups. After 5 years, an improvement was
      found for the dimensions 'desire for a child' [mean score 1.92 (T1) versus 1.72
      (T2)] and 'gender identity' [mean score 1.56 (T1) versus 1.42 (T2)] while no
      change was found for 'partnership' and 'psychological well-being'. We did not
      find significant differences between patients who had fathered a child in the
      meantime and patients who did not become fathers.

PMID- 23879210
TI  - Glycemic effects of vildagliptin and metformin combination therapy in Indian
      patients with type 2 diabetes: an observational study.
AB  - BACKGROUND: To analyze the glycemic response of Indian patients with type2
      diabetes mellitus (T2DM) to combination therapy with vildagliptin and metformin
      and compare our data with those of clinical trials. METHODS: In a retrospective
      study of the hospital database, the glycemic control of 280 patients with T2DM
      who were either on a once- or twice-daily regimen of combination therapy with
      vildagliptin 50 mg and metformin 500 mg was analyzed. RESULTS: The mean duration
      of follow-up of the patients was 16.8 months. There was a reduction in fasting
      plasma glucose (FPG) of 1.52 +/- 0.79 and 1.88 +/- 0.87 mmol/L in the once- and
      twice-daily groups, respectively (both P < 0.0001) from baseline to last visit.
      The reduction in postprandial plasma glucose (PPPG) in the once- and twice-daily
      groups was 3.98 +/- 1.72 and 4.33 +/- 1.88 mmol/L, respectively (both P <
      0.0001), whereas the reduction in HbA1c was 1.41 +/- 1.39% and 1.90 +/- 1.49%,
      respectively (both P < 0.0001). The differences in the reductions achieved in FPG
      and HbA1c with the two dosing regimens were significant. CONCLUSION: Although the
      present retrospective study shows a robust response to the combination of
      vildagliptin and metformin in Indian patients, more multicenter studies from
      India with a greater number patients are necessary to confirm this finding.

PMID- 23879212
TI  - 32nd congress of the scandinavian society of anaesthesiology and intensive care
      medicine, focusing on the brain, turku, Finland, 26-29 august 2013.

PMID- 23879211
TI  - Combining risk markers improves cardiovascular risk prediction in women.
AB  - Cardiovascular risk stratification could be improved by adding measures of
      atherosclerosis to current risk scores, especially in intermediate-risk
      individuals. We prospectively evaluated the additive value of different non
      invasive risk markers (both individual and combined) for gender-specific
      cardiovascular risk stratification on top of traditional risk factors in a middle
      aged population-based cohort. Carotid-plaques, IMT (intima-media thickness), ABI
      (ankle-brachial index), PWV (pulse-wave velocity), AIx (augmentation index), CAP
      (central augmented pressure) and CSP (central-systolic pressure) were measured in
      1367 CVD (cardiovascular disease)-free participants aged 50-70 years old.
      Cardiovascular events were validated after a mean follow-up of 3.8 years. AUC
      (area-under-the-curve) and NRI (net reclassification improvement) analyses (total
      NRI for all and clinical-NRI for intermediate-risk groups) were used to determine
      the additive value of individual and combined risk markers. Cardiovascular events
      occurred in 32 women and 39 men. Traditional cardiovascular risk factors
      explained 6.2% and 12.5% of the variance in CVD in women and men respectively.
      AUCs did not substantially increase by adding individual or combined non-invasive
      risk markers. Individual risk markers only improved reclassification in
      intermediate-risk women and more than in men; clinical-NRIs ranged between 48.0
      and 173.1% in women and 8.9 and 20% in men. Combined non-invasive-risk markers
      improved reclassification in all women and even more in those at intermediate
      risk; 'IMT-presence-thickness-of-plaques' showed largest reclassification [total
      NRI=33.8%, P=0.012; IDI (integrated-discrimination-improvement)=0.048, P=0.066;
      clinical-NRI=168.0%]. In men, combined non-invasive risk markers improved
      reclassification only in those at intermediate risk; 'PWV-AIx-CSP-CAP-IMT' showed
      the largest reclassification (total-NRI=14.5%, P=0.087; IDI=0.016, P=0.148;
      clinical-NRI=46.0%). In all women, cardiovascular risk stratification improved by
      adding combinations and in women at intermediate risk also by adding individual
      non-invasive risk markers. The additive value of individual and combined non
      invasive risk markers in men is limited to men at intermediate risk only, and to
      a lesser extent than in women.

PMID- 23879213
TI  - A new model for using quantitative urine testing as a diagnostic tool for
      oxycodone treatment and compliance.
AB  - We conducted a prospective, randomized, cross-sectional study to develop and
      validate a new model to predict oxycodone in urine that can be used to help
      evaluate whether patients are complying with their oxycodone dosing regimens. We
      studied 20 patients: eight black women, two white women, six black men, and four
      white men; ages 48 +/- 10 years (mean +/- SD); weight 97 +/- 32 kg. Pain levels
      before treatment averaged 9.5 +/- 0.9 out of 10. We prescribed oral oxycodone for
      each patient, tailoring the dosing regimen using clinical pharmacokinetics and
      measured the oxycodone concentration in each patient's urine 10 to 14 days after
      starting the dosing regimen. For each patient, we predicted oxycodone in their
      urine using our model, checked the actual concentration, and compared predicted
      with actual concentrations. For 18 of 20 patients (90%), actual results fell
      within +/-10% of our model's prediction. One patient was 35% below the
      prediction; the other was 51% above. Our model accurately predicts oxycodone in
      urine (+/-10% for 90% of the patients). The model appears clinically useful for
      evaluating the results of a quantitative urine test, since it objectively
      discriminates between (1) a "normal" patient complying with their oxycodone
      dosing regimen, and (2) a patient who may require genetic testing to distinguish
      between unusual metabolism or abuse.

PMID- 23879214
TI  - Estimates of charges associated with emergency department and hospital inpatient
      care for opioid abuse-related events.
AB  - The economic burden of prescription opioid abuse is substantial; however, no
      study has estimated the monetary burden of hospital services (emergency
      department [ED] and inpatient) using a single, nationally representative
      database. We sought to estimate total and average (adjusted for demographic and
      clinical factors) charges billed for opioid abuse-related events, and magnitude
      of difference in charges between ED visits resulting in inpatient admission to
      the same hospital and treat-and-release ED visits in the United States. We used
      the 2006, 2007, and 2008 files of the Healthcare Cost and Utilization Project's
      Nationwide Emergency Departments Sample (HCUP-NEDS) to identify events and
      charges assigned opioid abuse, dependence, or poisoning ICD-9-CM (International
      Classification of Diseases, 9th Revision, Clinical Modification) diagnosis codes
      (304.0X, 304.7X, 305.5X, 965.00, 965.02, 965.09). Using methods to account for
      the complex sampling design of the NEDS and a log-linked gamma regression model,
      we estimated national total and mean charges (in 2010 USD). Total charges were
      $9.8, $9.6, and $9.5 billion for 2006, 2007, and 2008, respectively. Medicaid
      covered events had the highest total charges ($3 billion), followed by events
      covered by Medicare ($2 billion) for each year. The national estimate of
      adjusted, mean, per-event charges, was $18,891 (95% confidence interval [CI] =
      $18,167-$19,616). Compared with events covered by private insurance, mean charges
      for Medicare- and Medicaid-covered events were higher (t = 28.14, P < .001; t =
      6.42, P < .001, respectively), whereas self-paid events had significantly lower
      charges (t = -11.14, P < .001). ED visits resulting in subsequent inpatient
      admission had approximately 6 times higher charges than treat-and-release visits.
      This study provides estimates of differences in hospital costs of opioid abuse by
      insurance status, resulting in a better understanding of the economic burden of
      opioid abuse on the health care system.

PMID- 23879216
TI  - Formulation by design of felodipine loaded liquid and solid self nanoemulsifying
      drug delivery systems using Box-Behnken design.
AB  - OBJECTIVE: To design and develop liquid and solid self-nanoemulsifying drug
      delivery systems (SNEDDS and S-SNEDDS) of felodipine (FLD) using Box-Behnken
      design (BBD). METHODS: Solubility study was carried out in various vehicles.
      Ternary phase diagram was constructed to delineate the boundaries of the
      nanoemulsion domain. The content of formulation variables, X1 (Acconon E), X2
      (Cremophor EL) and X3 (Lutrol E300) were optimized by assessment of 15
      formulations (as per BBD) for mean globule sizes in Millipore water (Y1), 0.1 N
      HCl (Y2), phosphate buffer (pH 6.4) (Y3); emulsification time (Y4) and T85% (Y5).
      The responses (Y1-Y5) were evaluated statistically by analysis of variance and
      response surface plots to obtain optimum points. The optimized formulations were
      solidified by adsorption to solid carrier technique using Aerosil 200 (AER).
      RESULTS AND DISCUSSION: Transmission electron microscopy images confirmed the
      spherical shape of globules with the size range concordant with the globule size
      analysis by dynamic light scattering technique (<60 nm). The surface morphology
      of S-SNEDDS (before release) by scanning electron microscopy and atomic force
      microscopy indicated that SNEDDS are adsorbed uniformly on the surface of AER.
      The dried residue of S-SNEDDS (after release) revealed the presence of nanometric
      pores vacated by the previously adsorbed SNEDDS onto AER. Differential scanning
      calorimetry and X-ray powder diffraction studies illustrated the change of FLD
      from crystalline to amorphous state. CONCLUSION: This study indicates that owing
      to nanosize, SNEDDS and S-SNEDDS of FLD have potential to enhance its absorption
      and may serve an efficient oral delivery.

PMID- 23879217
TI  - Do weight categories prevent athletes from relative age effect?
AB  - The aim of this study was to investigate whether weight categories prevent young
      athletes from being exposed to a relative age effect. The dates of birth of all
      French female (n = 727) and male (n = 5440) amateur boxers who participated in
      the 2010-2011 season were collected from the federation database. The dates of
      birth of all French male professional boxers (n = 354) were also collected. The
      results show an absence of a relative age effect among French female and male
      amateur boxers. The results also show an absence of this phenomenon among French
      male professional boxers. The male 18-18+ age category reveal an inverse relative
      age effect. This inverse relative age effect might be interpreted as the result
      of a strategic adaptation from relatively younger children who shift from one
      sport to another where there are weight categories in order to ensure fair
      competition. The results of this study suggest that the weight category system is
      a possible solution within the relative age effect phenomenon.

PMID- 23879218
TI  - Essential oils encapsulated in liposomes: a review.
AB  - In the recent years there has been an increased interest toward the biological
      activities of essential oils. However, essential oils are unstable and
      susceptible to degradation in the presence of oxygen, light and temperature. So,
      attempts have been made to preserve them through encapsulation in various
      colloidal systems such as microcapsules, microspheres, nanoemulsions and
      liposomes. This review focuses specifically on encapsulation of essential oils
      into liposomes. First, we present the techniques used to prepare liposomes
      encapsulating essential oils. The effects of essential oils and other factors on
      liposome characteristics such as size, encapsulation efficiency and thermal
      behavior of lipid bilayers are then discussed. The composition of lipid vesicles
      membrane, especially the type of phospholipids, cholesterol content, the molar
      ratio of essential oils to lipids, the preparation method and the kind of
      essential oil may affect the liposome size and the encapsulation efficiency.
      Several essential oils can decrease the size of liposomes, homogenize the
      liposomal dispersions, increase the fluidity and reduce the oxidation of the
      lipid bilayer. Moreover, liposomes can protect the fluidity of essential oils and
      are stable at 4-5  degrees C for 6 months at least. The applications of liposomes
      incorporating essential oils are also summarized in this review. Liposomes
      encapsulating essential oils are promising agents that can be used to increase
      the anti-microbial activity of the essential oils, to study the effect of
      essential oils on cell membranes, and to provide alternative therapeutic agents
      to treat several diseases.

PMID- 23879219
TI  - A new pyruvate oxidase biosensor based on 3-mercaptopropionic acid/6-aminocaproic
      acid modified gold electrode.
AB  - In the biosensor construction, 3-mercaptopropionic acid (3-MPA) and 6
      aminocaproic acid (6-ACA) were used for forming self-assembled monolayer (SAM) on
      a gold disc electrode and pyruvate oxidase was immobilized on the modified
      electrode surface by using glutaraldehyde. Biosensor response is linearly related
      to pyruvate concentration at 2.5-50 MUM, detection limit is 1.87 MUM and response
      time of the biosensor is 6 s for differential pulse voltammograms. From the
      repeatability studies (n = 6) for 30.0 MUM pyruvate revealed that the average
      value ([Formula: see text]), standard deviation (S.D) and coefficient of
      variation (CV %) were calculated to be 31.02 MUM, +/- 0.1914 MUM and 0.62%,
      respectively.

PMID- 23879220
TI  - Monitoring of the red-belted clearwing moth, Synanthedon myopaeformis, and its
      parasitoid Liotryphon crassiseta in apple orchards in yellow Moericke traps.
AB  - This study was conducted in 2008-2010 in three apple orchards in western Poland
      and involved a massive catch of the red-belted clearwing moth, Synanthedon
      myopaeformis (Borkhausen) (Lepidoptera: Sesiidae), and its parasitoid Liotryphon
      crassiseta (Thomson) (Hymenoptera: Ichneumonidae) in yellow Moericke traps. The
      flight time for both species was correlated and fell in the first half of July.
      However, the correlation between the occurrences of both species was
      statistically significant only in 2008, when most specimens were caught. A total
      of 7960 S. myopaeformis were caught, with a 2:1 male:female sex ratio, and 415
      adult L. crassiseta. No correlation between the numbers of S. myopaeformis and L.
      crassiseta in relation to age, variety of trees, or orchard surface area was
      noted. Significant differences between the catches of S. myopaeformis and L.
      crassiseta were reported in particular years. Furthermore, clear differences in
      the yields of S. myopaeformis and L. crassiseta between traps situated in the
      orchard and those on its edges were recorded, particularly in the orchard
      surrounded by cultivated fields. Yellow pan-traps could be used more widely in
      order to monitor and control the abundance of S. myopaeformis, especially by
      catching its females.

PMID- 23879222
TI  - Obesity and thyroid cancer: a clinical update.
AB  - BACKGROUND: In the last decade, significant contributions have been made to our
      knowledge on the connection between the thyroid and adipose tissue. Modern
      society is faced with climbing rates of obesity and metabolic syndrome, and there
      is accumulating evidence of an association between obesity and increased cancer
      risk. The aim of this review is to summarize clinical data on the association
      between thyroid cancer (TC) and obesity and briefly to present plausible
      hypotheses explaining this interplay. SUMMARY: We performed a search on the
      PubMed database for studies published in English from 1980 to March 2013 using
      the terms "thyroid cancer," "obesity," and "body mass index." Although there is
      inconsistency among the clinical studies, it seems that overweight and obesity
      are related to a modestly increased TC risk. Various factors, such as sex,
      ethnicity, and body changes during certain life periods, for example adolescence,
      may influence the association between obesity and TC risk. There are preliminary
      data linking obesity with a less favorable clinicopathologic profile of TC.
      However, validation with larger multicenter studies is needed. The precise
      underlying mechanisms have not yet been elucidated, but the insulin-IGF axis and
      adipokines, such as leptin and adiponectin, might be implicated in the link
      between excess weight and TC. CONCLUSIONS: Given the rising prevalence of TC and
      the development of obesity as an epidemic, it is important to clarify its
      connection with TC as well as the mediating pathways. However, unless this
      association is confirmed and causation proven, screening for TC in overweight and
      obese subjects-a rapidly increasing body of the general population-does not seem
      justified.

PMID- 23879223
TI  - Surgical treatment of retinal detachment associated with degenerative
      retinoschisis.
AB  - PURPOSE: Although degenerative retinoschisis is almost always asymptomatic,
      retinal detachment occurs in some patients with outer layer breaks (OLBs). The
      purpose of this study is to evaluate the different surgical techniques used for
      the treatment of this condition. METHODS: Retrospective interventional case
      series. The patients underwent either a Scleral-Buckling procedure (SB) or a 3
      port pars plana vitrectomy (V). Pre-, intra-, and post-operative data were
      analyzed for the two groups. RESULTS: Thirty eyes of 30 consecutive patients were
      included in the analysis. There was a statistically significant difference (0.5
      +/- 0.48 LogMAR units for the SB group, 1.37 +/- 1.4 LogMAR units for the V
      group, p = 0.027) in final BCVA when the two groups were compared, whereas there
      was no statistically significant difference in the baseline BCVA between the two
      groups (p = 0.38). The proportion of cases that were successfully attached with
      one operation was slightly lower in the V group (62% versus 76%). Conversely, the
      proportion of cases that were successfully attached with more than one operation
      was similar in both groups (23% and 24%, respectively). CONCLUSION: The present
      study highlights that retinoschisis-associated RD is a demanding situation to
      treat and remains a challenge for vitreoretinal surgeons. Scleral buckle
      procedure was found to be successful in eyes that have peripheral OLBs and not
      extensive RDs, and PPV should be considered for treating symptomatic, rather
      extensive schisis-RDs, especially in cases with large or posterior outer layer
      breaks.

PMID- 23879224
TI  - Repair of iridodialysis using 8-0 polypropylene.
AB  - PURPOSE: Investigate the effectiveness of repair of iridodialysis with 8-0
      polypropylene. METHODS: We present four cases of traumatic iridodialysis that
      were repaired by 8-0 polypropylene suture. RESULTS: Better iris reposition and
      stability were achieved with 8-0 polypropylene suture despite wide degree
      traumatic iridodialysis in all patients. CONCLUSION: In this study, we used 8-0
      polypropylene suture, which is thicker, cheaper, and more durable than 10-0
      sutures. We suggest that usage of 8-0 polypropylene sutures may provide better
      iris repositioning.

PMID- 23879225
TI  - Skin barrier impairment correlates with cutaneous Staphylococcus aureus
      colonization and sensitization to skin-associated microbial antigens in adult
      patients with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. The
      pathogenesis of AD involves skin barrier defects and dysregulation of innate and
      adaptive immunity. Some environmental factors such as stress, infections, and
      allergens are associated with aggravation of AD. The aim of the study was to
      investigate the relationship between skin barrier function, skin colonization of
      Staphylococcus aureus, and sensitization to antigens of skin-associated
      microorganisms in adult patients with AD. METHODS: Thirty adult patients with AD
      and 10 controls were recruited. Eczema severity was assessed, and transepidermal
      water loss (TEWL) was measured. Bacterial samples were taken from the skin using
      a swab technique for qualitative identification of S. aureus and a contact agar
      disc method for quantitative assessment. Immunological analyses of specific IgE
      to staphylococcal enterotoxins and yeasts as well as total serum IgE levels, were
      performed. RESULTS: TEWL was significantly higher among S. aureus-positive
      patients in comparison to S. aureus-negative patients with AD (P < 0.05). TEWL
      increased with increasing bacterial load (P = 0.018). In the group of patients
      sensitized to all three of the investigated skin-associated microorganisms (S.
      aureus, Malassezia, and Candida), an increased TEWL was observed, in comparison
      to patients sensitized to none, or one or two (P = 0.026). CONCLUSION: In adult
      patients with AD, a disrupted skin barrier promotes skin colonization by
      microbes, such as S. aureus. Heavy microbial colonization may facilitate skin
      penetration of microbial antigens leading to subsequent IgE sensitization. These
      results illustrate the importance of skin-associated microbial colonization and
      sensitization to microbial-derived allergens in eczema pathogenesis.

PMID- 23879227
TI  - Potential P-glycoprotein pharmacokinetic interaction of telaprevir with morphine
      or methadone.
AB  - Telaprevir (TVR) effects on P-glycloprotein and cytochrome P450 (CYP) may
      significantly elevate serum levels of morphine and methadone. Recent literature
      points to major interactions when combining TVR with warfarin or rifampin. Opioid
      interactions are especially dangerous in hepatitis C patients, as coinfection
      with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs in 50
      90% of HIV-infected drug users that are prescribed opioids for chronic pain
      and/or methadone for maintenance. TVR has been shown to significantly inhibit the
      active transport enzyme pGP and may therefore increase intestinal morphine
      absorption. TVR also inhibits hepatic CYP3A4 that are responsible for
      metabolizing methadone. Patients requiring opioid analgesics must be carefully
      monitored because of potential for elevated opioid levels and overdose risk.
      Current recommendations minimize potential drug interactions between telaprevir
      and opioids, especially methadone, based on a single 7-day trial. We outline the
      various pharmacokinetic mechanisms involved when combining TVR with methadone or
      morphine and recommend that current data are not sufficiently robust to minimize
      the potentially significant interaction with opioids, especially methadone.
      Clinicians must be mindful of these understated interactions, know that the
      opioid dose may need to be significantly increased or reduced, and use caution
      during upward titration of opioids affected by these enzyme systems.

PMID- 23879226
TI  - Design and methods of the Hospital Elder Life Program (HELP), a multicomponent
      targeted intervention to prevent delirium in hospitalized older patients:
      efficacy and cost-effectiveness in Dutch health care.
AB  - BACKGROUND: The Hospital Elder Life Program (HELP) has been shown to be highly
      efficient and (cost-)effective in reducing delirium incidence in the USA. HELP
      provides multicomponent protocols targeted at specific risk factors for delirium
      and introduces a different view on care organization, with trained volunteers
      playing a pivotal role. The primary aim of this study is the quantification of
      the (cost-)effectiveness of HELP in the Dutch health care system. The second aim
      is to investigate the experiences of patients, families, professionals and
      trained volunteers participating in HELP. METHODS/DESIGN: A multiple baseline
      approach (also known as a stepped-wedge design) will be used to evaluate the
      (cost-) effectiveness of HELP in a cluster randomized controlled study. All
      patients aged 70 years and older who are at risk for delirium and are admitted to
      cardiology, internal medicine, geriatrics, orthopedics and surgery at two
      participating community hospitals will be included. These eight units are
      implementing the intervention in a successive order that will be determined at
      random. The incidence of delirium, the primary outcome, will be measured with the
      Confusion Assessment Method (CAM). Secondary outcomes include the duration and
      severity of delirium, quality of life, length of stay and the use of care
      services up to three months after hospital discharge. The experiences of
      patients, families, professionals and volunteers will be investigated using a
      qualitative design based on the grounded theory approach. Professionals and
      volunteers will be invited to participate in focus group interviews.
      Additionally, a random sample of ten patients and their families from each
      hospital unit will be interviewed at home after discharge. DISCUSSION: We
      hypothesize that HELP will reduce delirium incidence during hospital admission
      and decrease the duration and severity of delirium and length of hospital stays
      among these older patients, which will lead to reduced health care costs. The
      results of this study may fundamentally change our views on care organization for
      older patients at risk for delirium. The stepped-wedge design was chosen for
      ethical, practical and statistical reasons. The study results will be
      generalizable to the Dutch hospital care system, and the proven cost
      effectiveness of HELP will encourage the spread and implementation of this
      program. TRIAL REGISTRATION: Netherlands Trial register: NTR3842.

PMID- 23879228
TI  - Rational design of DNA motors: fuel optimization through single-molecule
      fluorescence.
AB  - While numerous DNA-based molecular machines have been developed in recent years,
      high operational yield and speed remain a major challenge. To understand the
      reasons for the limited performance, and to find rational solutions, we applied
      single-molecule fluorescence techniques and conducted a detailed study of the
      reactions involved in the operation of a model system comprised of a bipedal DNA
      walker that strides on a DNA origami track powered by interactions with fuel and
      antifuel strands. Analysis of the kinetic profiles of the leg-lifting reactions
      indicates a pseudo-first-order antifuel binding mechanism leading to a rapid and
      complete leg-lifting, indicating that the fuel-removal reaction is not
      responsible for the 1% operational yield observed after six steps. Analysis of
      the leg-placing reactions showed that although increased concentrations of fuel
      increase the reaction rate, they decrease the yield by consecutively binding the
      motor and leading to an undesirable trapped state. Recognizing this, we designed
      asymmetrical hairpin-fuels that by regulating the reaction hierarchy avoid
      consecutive binding. Motors operating with the improved fuels show 74% yield
      after 12 consecutive reactions, a dramatic increase over the 1% observed for
      motors operating with nonhairpin fuels. This work demonstrates that studying the
      mechanisms of the reactions involved in the operation of DNA-based molecular
      machines using single-molecule fluorescence can facilitate rationally designed
      improvements that increase yield and speed and promote the applicability of DNA
      based machines. 

PMID- 23879229
TI  - Evolution of symbiosis in the legume genus Aeschynomene.
AB  - Legumes in the genus Aeschynomene form nitrogen-fixing root nodules in
      association with Bradyrhizobium strains. Several aquatic and subaquatic species
      have the additional capacity to form stem nodules, and some of them can
      symbiotically interact with specific strains that do not produce the common Nod
      factors synthesized by all other rhizobia. The question of the emergence and
      evolution of these nodulation characters has been the subject of recent debate.
      We conducted a molecular phylogenetic analysis of 38 different Aeschynomene
      species. The phylogeny was reconstructed with both the chloroplast DNA trnL
      intron and the nuclear ribosomal DNA ITS/5.8S region. We also tested 28
      Aeschynomene species for their capacity to form root and stem nodules by
      inoculating different rhizobial strains, including nodABC-containing strains
      (ORS285, USDA110) and a nodABC-lacking strain (ORS278). Maximum likelihood
      analyses resolved four distinct phylogenetic groups of Aeschynomene. We found
      that stem nodulation may have evolved several times in the genus, and that all
      Aeschynomene species using a Nod-independent symbiotic process clustered in the
      same clade. The phylogenetic approach suggested that Nod-independent nodulation
      has evolved once in this genus, and should be considered as a derived character,
      and this result is discussed with regard to previous experimental studies. 

PMID- 23879231
TI  - Deep vein thrombosis and lung cancer in a patient with psoriasis under anti-tumor
      necrosis factor treatment: a case study.
AB  - We describe a case of a patient with severe generalized psoriasis treated with
      etanercept, who developed deep vein thrombosis and 1 year later developed solid
      lung cancer. Anti-tumor necrosis factor therapies have been a powerful addition
      to the therapy of psoriasis; nevertheless, the treatment might be associated with
      adverse events, such as venous thromboembolism or malignancies. Available data
      regarding these specific adverse reactions are rather conflictive; therefore,
      more observational studies and registry reports for long-term risk assessment are
      needed.

PMID- 23879230
TI  - Multilocus phylogeography of the European ground squirrel: cryptic interglacial
      refugia of continental climate in Europe.
AB  - The theory of classical and cryptic Pleistocene refugia is based mainly on
      historical changes in temperature, and the refugia are usually defined within a
      latitudinal gradient. However, the gradient of oceanic-continental climate (i.e.
      longitudinal) was also significantly variable during glacial cycles with
      important biotic consequences. Range-wide phylogeography of the European ground
      squirrel (EGS) was used to interpret the evolutionary and palaeogeographical
      history of the species in Europe and to shed light on its glacial-interglacial
      dynamic. The EGS is a steppe-inhabiting species and the westernmost member of the
      genus in the Palaearctic region. We have analysed 915 specimens throughout the
      present natural range by employing mitochondrial DNA sequences (cytochrome b
      gene) and 12 nuclear microsatellite markers. The reconstructed phylogeography
      divides the species into two main geographical groups, with deep substructuring
      within both groups. Bulgaria is the centre of the ancestral area, and it also has
      the highest genetic diversity within the species. The northernmost group of the
      EGS survived in the southern part of Pannonia throughout several glacial
      interglacial cycles. Animals from this population probably repeatedly colonized
      areas further to the north and west during the glacial periods, while in the
      interglacial periods, the EGS distribution contracted back to this Pannonian
      refugium. The EGS thus represents a species with a glacial expansion/interglacial
      contraction palaeogeographical dynamics, and the Pannonian and southeastern
      Balkanian steppes are supported as cryptic refugia of continental climate during
      Pleistocene interglacials. 

PMID- 23879232
TI  - Low-income women's recommendations for promoting early pregnancy recognition.
AB  - INTRODUCTION: This study explored low-income women's perspectives on how to
      promote early recognition of pregnancy as one strategy to address community
      residents' concerns related to unintended pregnancy. Unintended pregnancy, which
      is more prevalent among low-income women and minorities, has been associated with
      various adverse pregnancy outcomes. METHODS: This study used the ideological
      perspective of community-based participatory research. Six focus groups were
      conducted in 3 low-income, urban, medically underserved neighborhoods with
      ethnically diverse populations. Neighborhood women who were either pregnant or
      had experienced a pregnancy within 3 years were invited to participate in the
      study. A structured interview guide focused the discussion on how to promote
      early recognition of pregnancy within the existing context of unintended
      pregnancies in the neighborhoods. Focus-group sessions were audiotaped, then
      transcribed verbatim; the data were analyzed using an open-coding template
      approach assisted by QSR NVivo 8 software. RESULTS: Forty-one women aged 18 to 44
      years participated in the study. Thirty-nine percent were African American, 24.4%
      were Hispanic/Latino, 19.5% were American Indians, and 17.1% were white. Three
      primary themes were identified: 1) women should know the menstrual/ovulation and
      pregnancy-related changes that occur in their bodies; 2) women should be prepared
      to confirm their pregnancies early, as soon as they suspect they may be pregnant;
      and 3) both information and emotional support are needed for pregnancy-related
      issues. "Knowing your body" was the strongest advice to promote early recognition
      of pregnancy. DISCUSSION: The participants in this study suggested that education
      about reproductive changes should be initiated during early adolescence and in
      the preconception period. Early testing and confirmation of pregnancy should also
      be promoted, especially for women who have unprotected intercourse. Local
      resources for information and emotional support during pregnancy should be
      accessible to women.

PMID- 23879233
TI  - Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and
      insulin/IGF-1 signaling pathways in C. elegans.
AB  - Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway
      that regulates various physiologic processes, including aging and metabolism. One
      of the key downstream components of TOR signaling is ribosomal protein S6 kinase
      (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans,
      Drosophila, and mice. Here, we demonstrate that the activation of heat shock
      factor 1 (HSF-1), a crucial longevity transcription factor known to act
      downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged
      lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1
      is required for the longevity caused by down-regulation of components in TOR
      signaling pathways, including TOR and S6K. The induction of a small heat-shock
      protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of
      rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is
      required for the further enhanced longevity caused by simultaneous down
      regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an
      essential longevity factor that intersects both IIS and TOR signaling pathways. 

PMID- 23879234
TI  - Mometasone fuoroate 0.1% ointment in the treatment of vulvar lichen sclerosus: a
      study of efficacy and safety on a large cohort of patients.
AB  - BACKGROUND: Guidelines identify a 3-month topical application of an ultra-potent
      corticosteroid ointment as the mainstay of medical treatment for vulvar lichen
      sclerosus (VLS). However, there are no trials providing evidence that any
      specific corticosteroid is superior to another. OBJECTIVE: To assess the
      effectiveness and safety of a 12-week application of mometasone furoate (MMF)
      0.1% ointment, with a tapering regimen, in achieving control of VLS signs and
      symptoms and to detect potential risk factors for VLS non-response. METHODS: 147
      patients affected with VLS were enrolled in a 12-week active treatment phase
      (ATP) with topical 0.1% MMF. The primary efficacy endpoint was the rate of
      patients achieving clinical response, as defined by protocol parameters. The
      secondary efficacy endpoint was to assess the changes of mean VLS-related
      symptoms after the 12-week ATP compared with baseline. RESULTS: By the end of the
      ATP, 113 patients (80.7%) experienced a treatment response, whereas 27 women
      (19.3%) were judged as non-responders. Mean symptom scores decreased
      significantly in the study patients, regardless of their clinical response at the
      end of the ATP. Among all the epidemiological and clinical data considered, only
      the absence of previous medical therapies was found to be related to a
      significantly higher risk of non-response to treatment. CONCLUSIONS: Application
      of 0.1% MMF ointment for 12 weeks on a tapering regimen was found to be an
      effective and safe therapy option in the ATP of VLS and could represent an
      alternative first-line treatment to an ultra-potent molecule.

PMID- 23879235
TI  - Evolution of sperm quality in men living in the vicinity of a municipal solid
      waste incinerator possibly correlated with decreasing dioxins emission levels.
AB  - The objective was to examine the impact on sperm parameters of environmental
      exposure to dioxins around a municipal waste incinerator initially with high
      emission levels and during reduction levels. An ecological study with quasi
      experimental conditions was performed in patients of a reproductive laboratory.
      The first semen analyses of 251 men living in Besancon, France, between 2001 and
      2007, were included. To analyse the contribution of direct exposure (inhalation),
      the calendar time was dichotomised in two periods 2001-2003 versus 2004-2007 and
      used as a proxy for exposure. Regarding the indirect exposure pathway (food), the
      statistical analysis was made with a nonparametric test to assess the trends.
      There was a negative correlation between the year of exposure and the percentage
      of abnormal mid-piece and the multiple abnormalities index, even after adjusting
      for age and days abstention from inter-course. A positive correlation was found
      between the progressive motile sperm count and the period of exposure. These
      findings are to be put into the context of a drastic reduction in emissions of
      dioxins. Our results suggest an effect of chronic exposure to dioxins on
      spermiogenesis with more abnormalities. These results should be confirmed with
      concentration measurements of dioxins in infertile men. 

PMID- 23879236
TI  - Diet in the early years of life influences cognitive outcomes at 10 years: a
      prospective cohort study.
AB  - AIM: The aim of this study was to investigate the association between diet during
      the first 3 years of life and cognitive outcomes at 10 years of age. METHODS: The
      Raine Study is a longitudinal study of 2868 children and their families. Based on
      the foods reported to be eaten at age one, two and three, an Eating Assessment in
      Toddlers diet score was developed, consisting of seven components. Cognition was
      measured by the Peabody Picture Vocabulary Test-III (PPVT-III) and the Raven's
      Coloured Progressive Matrices at the 10-year follow-up. Associations were
      assessed in multivariate regression models. RESULTS: A higher Eating Assessment
      in Toddlers diet score at age one was associated with higher PPVT-III [beta =
      0.12 (0.05, 0.19), p = 0.001] and Raven's Coloured Progressive Matrices scores
      [beta = 0.17 (0.02, 0.33), p = 0.025] at age ten after adjustments. Increased
      fruit consumption at age one was positively associated, while increased sweetened
      beverage consumption was negatively associated with cognitive development. Dairy
      consumption at ages two and three had positive associations with the PPVT-III and
      at age two with the Raven's Coloured Progressive Matrices. CONCLUSION: A better
      diet quality during the early years of life may have a positive effect on
      cognitive ability later in childhood.

PMID- 23879238
TI  - Vibrational spectra and fragmentation pathways of size-selected, D2-tagged
      ammonium/methylammonium bisulfate clusters.
AB  - Particles consisting of ammonia and sulfuric acid are widely regarded as seeds
      for atmospheric aerosol nucleation, and incorporation of alkylamines has been
      suggested to substantially accelerate their growth. Despite significant efforts,
      little direct experimental evidence exists for the structures and chemical
      processes underlying multicomponent particle nucleation. Here we are concerned
      with the positively charged clusters of ammonia and sulfuric acid with
      compositions H(+)(NH3)m(H2SO4)n (2 <= m <= 5, 1 <= n <= 4), for which equilibrium
      geometry structures have been reported in recent computational searches. The
      computed harmonic vibrational spectra of such minimum energy structures can be
      directly compared with the experimental spectra of each cluster composition
      isolated in the laboratory using cryogenic ion chemistry methods. We present one
      photon (i.e., linear) infrared action spectra of the isolated gas phase ions
      cryogenically cooled to 10 K, allowing us to resolve the characteristic
      vibrational signatures of these clusters. Because the available calculated
      spectra for different structural candidates have been obtained using different
      levels of theory, we reoptimized the previously reported structures with several
      common electronic structure methods and find excellent agreement can be achieved
      for the (m = 3, n = 2) cluster using CAM-B3LYP with only minor structural
      differences from the previously identified geometries. At the larger sizes, the
      experimental spectra strongly resemble that observed for 180 nm ammonium
      bisulfate particles. The characteristic ammonium- and bisulfate-localized bands
      are clearly evident at all sizes studied, indicating that the cluster structures
      are indeed ionic in nature. With the likely (3,2) structure in hand, we then
      explore the spectral and structural changes caused when methylamine is
      substituted for ammonia. This process is found to occur with minimal perturbation
      of the unsubstituted cluster. The thermal decomposition pathways were also
      evaluated using multiple-photon induced dissociation and are, in all cases,
      dominated (>100:1) by evaporation of a neutral ammonia molecule rather than
      methylamine. Spectra obtained for the product cluster ions resulting from this
      evaporation are consistent with the formation of a single hydrogen bond between
      two neighboring bisulfate ions, partially regenerating a sulfuric acid molecule.
      These results provide critical experimental benchmarks for ongoing theoretical
      efforts to understand the early stages of aerosol growth. 

PMID- 23879239
TI  - Logic-gate devices based on printed polymer semiconducting nanostripes.
AB  - The applications of organic semiconductors in complex circuitry such as printed
      CMOS-like logic circuits demand miniaturization of the active structures to the
      submicrometric and nanoscale level while enhancing or at least preserving the
      charge transport properties upon processing. Here, we addressed this issue by
      using a wet lithographic technique, which exploits and enhances the molecular
      order in polymers by spatial confinement, to fabricate ambipolar organic field
      effect transistors and inverter circuits based on nanostructured single component
      ambipolar polymeric semiconductor. In our devices, the current flows through a
      precisely defined array of nanostripes made of a highly ordered
      diketopyrrolopyrrole-benzothiadiazole copolymer with high charge carrier mobility
      (1.45 cm(2) V(-1) s(-1) for electrons and 0.70 cm(2) V(-1) s(-1) for holes).
      Finally, we demonstrated the functionality of the ambipolar nanostripe
      transistors by assembling them into an inverter circuit that exhibits a gain
      (105) comparable to inverters based on single crystal semiconductors. 

PMID- 23879240
TI  - Influence of different keratoplasty techniques on the biomechanical properties of
      the cornea.
AB  - PURPOSE: To evaluate and compare corneal biomechanical changes after deep
      anterior lamellar keratoplasty (DALK) versus penetrating keratoplasty (PK) using
      the ocular response analyzer (ORA). METHODS: This prospective comparative study
      included 65 eyes (65 patients). Patients were divided into three groups: DALK (20
      eyes), PK (25 eyes) and control group of normal subjects (20 eyes). Ocular
      response analyzer was used to measure corneal hysteresis (CH), corneal resistance
      factor (CRF), Goldmann-correlated intraocular pressure and cornea-compensated
      intraocular pressure at 6 and 12 months postoperatively. Central corneal
      thickness (CCT) was measured using ultrasonic pachymetry. RESULTS: Both mean CH
      and mean CRF were significantly lower in PK group (sutures on; 10.1 +/- 1.11 and
      9.6 +/- 1.08 mmHg) than in DALK (sutures out; 12.25+/- 1.13 and 12.09 +/- 1.05
      mmHg) and control groups (12.98 +/- 1.19 and 12.59 +/- 0.94 mmHg) at 6 months,
      respectively (p <0.0001). After 1 year, there was no statistically significant
      difference in mean CH and CRF between DALK (12.68 +/- 1.11 and 12.18 +/- 1.11
      mmHg) and PK groups (still sutures on; 12.36 +/- 1.32 mmHg, p = 0.39 and 11.83 +/
      1.26 mmHg, p = 0.33, respectively); however, the mean CRF was significantly
      lower in the PK than the control group (p = 0.03). No statistically significant
      difference in mean CH or mean CRF was found between DALK and control groups at
      any time-point. CONCLUSIONS: Compared with PK, DALK provides rapid return of
      normal corneal biomechanics, perhaps because of the combined healing at both the
      deep interface and graft margin, shorter period of steroid treatment and the
      intactness of Descemet membrane in these eyes.

PMID- 23879241
TI  - (99m)Tc-labeled therapeutic inhaled amikacin loaded liposomes.
AB  - The radiolabeling of the liposome surface can be a useful tool for in vivo
      tracking of therapeutic drug loaded liposomes. We investigated radiolabeling
      therapeutic drug (i.e. an antibiotic, amikacin) loaded liposomes with (99m)Tc,
      nebulization properties of (99m)Tc-labeled liposomal amikacin for inhalation
      ((99m)Tc-LAI), and its stability by size exclusion low-pressure liquid
      chromatography (LPLC). LAI was reacted with (99m)Tc using SnCl2 dissolved in
      ascorbic acid as a reducing agent for 10 min at room temperature. The labeled
      products were then purified by anion exchange resin. The purified (99m)Tc-LAI in
      1.5% NaCl solution was incubated at 4  degrees C to assess its stability by LPLC.
      The purified (99m)Tc-LAI was subjected to studies with a clinically used
      nebulizer (PARI eFlow(r)) and the Anderson Cascade Impactor (ACI). The use of
      ascorbic acid at 0.91 mM resulted in a quantitative labeling efficiency. The LPLC
      profile showed that the liposomal peak of LAI detected by a UV monitor at both
      200 nm and 254 nm overlapped with the radioactivity peak of (99m)Tc-LAI,
      indicating that (99m)Tc-LAI is suitable for tracing LAI. The ACI study
      demonstrated that the aerosol droplet size distribution determined
      gravimetrically was similar to that determined by radioactivity. The liposome
      surface labeling method using SnCl2 in 0.91 mM ascorbic acid produced (99m)Tc-LAI
      with a high labeling efficiency and stability that are adequate to evaluate the
      deposition and clearance of inhaled LAI in the lung by gamma scintigraphy.

PMID- 23879243
TI  - Bipedicled skin flap in the treatment of divided nevus of the eyelid.

PMID- 23879245
TI  - Evaluation of systemic exposure of nanoparticle suspensions subcutaneously
      administered to mice regarding stabilization, volume, location, concentration and
      size.
AB  - Different routes of administration are likely to result in very different
      outcomes due to different availability or plasma profile. The objective of the
      present study was to evaluate the pharmacokinetic profile after different
      subcutaneous (s.c.) administration of nanoparticle suspensions of a lipophilic
      compound to mice. Pharmacokinetics of the selected test compound and the effect
      of drug concentration, particle size, location of administration, volume given
      and particle stabilizers were studied. Adding PEGylated lipids or pluronic F-127
      to the negatively charged surface of the nanoparticles increased the stability of
      the particles and the bioavailability. The in vivo studies demonstrated linear
      absorption kinetics for the selected model compound up to at least 500 umol/kg.
      Absorption from upper-neck resulted in different systemic exposure compared to
      administration in the hip. The former was preferred if a prolonged Cmax was
      desired while the latter ensured a flat profile for approximately 24 hours.
      Administering the double volume (but the same dose) had no effect on the
      pharmacokinetics, whereas smaller particle size significantly increased the
      exposure.

PMID- 23879244
TI  - Hypothalamic apelin/reactive oxygen species signaling controls hepatic glucose
      metabolism in the onset of diabetes.
AB  - AIMS: We have previously demonstrated that central apelin is implicated in the
      control of peripheral glycemia, and its action depends on nutritional (fast
      versus fed) and physiological (normal versus diabetic) states. An
      intracerebroventricular (icv) injection of a high dose of apelin, similar to that
      observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that
      apelin contributes to the establishment of a diabetic state, and (ii) the
      existence of a hypothalamic to liver axis. Using pharmacological, genetic, and
      nutritional approaches, we aim at unraveling this system of regulation by
      identifying the hypothalamic molecular actors that trigger the apelin effect on
      liver glucose metabolism and glycemia. RESULTS: We show that icv apelin injection
      stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the
      sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of
      central apelin on liver function is dependent of an increased production of
      hypothalamic reactive oxygen species (ROS). These data are strengthened by
      experiments using lentiviral vector-mediated over-expression of apelin in
      hypothalamus of mice that present over-activation of SNS associated to an
      increase in hepatic glucose production. Finally, we report that mice fed a high
      fat diet present major alterations of hypothalamic apelin/ROS signaling, leading
      to activation of glycogenolysis. INNOVATION/CONCLUSION: These data bring
      compelling evidence that hypothalamic apelin is one master switch that
      participates in the onset of diabetes by directly acting on liver function. Our
      data support the idea that hypothalamic apelin is a new potential therapeutic
      target to treat diabetes.

PMID- 23879246
TI  - Do all portable cases constructed by caddisfly larvae function in defense?
AB  - The portable cases constructed by caddisfly larvae have been assumed to act as a
      mechanical defense against predatory attacks. However, previous studies have
      compared the survival of caddisflies with different cases, thereby precluding an
      analysis of the survival benefits of "weaker" case materials. The level of
      protection offered by caddisfly cases constructed with rock, stick, or leaf
      material, as well as a no-case control, was investigated against predatory
      dragonfly nymphs (Anax junius Drury (Anisoptera: Aeshnidae)). A valid supposition
      is that the cases made of stronger material are more effective at deterring
      predators. Yet, observations revealed that there was no difference in survival
      between the case types. All caddisflies with a case experienced high survival in
      comparison to caddisflies removed from their case. In addition, larvae with stick
      cases experienced fewer attacks and captures by dragonflies. These results showed
      that the presence of a case, regardless of the material used in its construction,
      offers survival benefits when faced with predatory dragonfly nymphs.

PMID- 23879247
TI  - Dermatologic toxicities to targeted cancer therapy: shared clinical and
      histologic adverse skin reactions.
AB  - BACKGROUND: Dermatologic toxicities (DT) to targeted cancer therapy may present
      as inflammatory dermatoses, keratoses, and as benign and malignant squamous
      proliferations. METHODS: Published reports of DT with cancer therapy with
      epidermal growth factor receptor (EGFR), tyrosine kinase (TK), MEK, PI3K, AKT,
      and BRAF inhibitors were reviewed. RESULTS: DT associated with targeted cancer
      therapy demonstrated similar reactions and may be grouped as (i) DT as cutaneous
      inflammation, and (ii) DT as cutaneous epithelial proliferation. EGFR inhibitor,
      cetuximab, and MEK inhibitors, selumetinib and trametinib, demonstrated
      papulopustular rash with a suppurative folliculitis in 83%, 93%, and 80% of the
      patients on therapy, respectively. Common DT with EGFR inhibitors erlotinib and
      tyrosine kinase inhibitor sorafenib were hand-foot skin reactions in 30-60% of
      patients on therapy. PI3K inhibitor BKM-120 and AKT inhibitor MK2206 produced
      maculopapular eruptions seen as dermal hypersensitivity reaction on the skin
      biopsy. RAF inhibitors vemurafenib and sorafenib were associated with a variety
      of cutaneous epithelial proliferations (keratosis pilaris, seborrheic keratosis,
      verruca vulgaris, actinic keratosis, keratoacanthoma, and squamous cell
      carcinoma. CONCLUSION: Various anticancer agents may target similar cellular
      compounds and/or cell signaling pathways thus share similar clinical and
      histologic features of DT. The knowledge of the overlap of DT with different
      types of targeted cancer therapy will assist in evaluation of cutaneous
      reactions.

PMID- 23879248
TI  - The effects of isometric wall squat exercise on heart rate and blood pressure in
      a normotensive population.
AB  - The isometric wall squat could be utilised in home-based training aimed at
      reducing resting blood pressure, but first its suitability must be established.
      The aim of this study was to determine a method of adjusting wall squat intensity
      and explore the cardiovascular responses. Twenty-three participants performed one
      2 minute wall squat on 15 separate occasions. During the first ten visits, ten
      different knee joint angles were randomly completed from 135 degrees  to 90
      degrees  in 5 degrees  increments; five random angles were repeated in subsequent
      visits. Heart rate and blood pressure (systolic, diastolic and mean arterial
      pressure) were measured. The heart rate and blood pressure parameters produced
      significant inverse relationships with joint angle (r at least -0.80; P < 0.05),
      demonstrating that wall squat intensity can be adjusted by manipulating knee
      joint angle. Furthermore, the wall squat elicited similar cardiovascular
      responses to other isometric exercise modes that have reduced resting blood
      pressure (135 degrees  heart rate: 76 +/- 10 beats ? min(-1); systolic: 134 +/-
      14 mmHg; diastolic: 76 +/- 6 mmHg and 90 degrees  heart rate: 119 +/- 20 beats ?
      min(-1); systolic: 196 +/- 18 mmHg; diastolic: 112 +/- 13 mmHg). The wall squat
      may have a useful role to play in isometric training aimed at reducing resting
      blood pressure.

PMID- 23879249
TI  - Conjunctival flora, Schirmer's tear test, intraocular pressure, and conjunctival
      cytology in neotropical primates from Salvador, Brazil.
AB  - BACKGROUND: This study aimed to establish reference values for selected
      ophthalmic diagnostic tests in healthy neotropical primates from Salvador,
      Brazil. METHODS: A total of 73 intact adults, including Callithrix jacchus (n =
      31), Callithrix penicillata (n = 8), Cebus sp. (n = 22), and Cebus xanthosternos
      (n = 9) were used to evaluate the normal conjunctival bacterial flora. Cebus
      xanthosternos (n = 12) were used to evaluate tear production with Schirmer's tear
      test (STT), intraocular pressure (IOP), and conjunctival cytology. RESULTS: For
      all animals evaluated, Gram-positive bacteria were predominant. Results of the
      diagnostic tests in Cebus xanthosternos were as follows: STT: 14.92 +/- 5.46
      mm/minutes, IOP: 19.62 +/- 4.57 mmHg, and conjunctival cytology revealed
      intermediate squamous epithelial cells in great quantities. CONCLUSIONS: These
      ophthalmic reference values will be particularly useful to diagnose discrete or
      unusual pathological changes in the neotropical primates eye.

PMID- 23879251
TI  - Clinical efficacy of antibiotics in the treatment of peri-implantitis.
AB  - OBJECTIVES: The aim of the present study was to review the pertinent literature
      with reference to the clinical efficacy of antibiotics in the treatment of peri
      implantitis. METHODS: To address the focused question 'Are locally and
      systemically delivered antibiotics useful in the treatment of peri-implantitis?'
      PubMed/Medline and Google-scholar databases were explored from 1992 until
      February 2013 using a combination of the following keywords: 'antibiotic,'
      'dental implant,' 'inflammation,', 'peri-implantitis' and 'treatment'. Letters to
      the editor, case-reports and unpublished data were excluded. RESULTS: Ten studies
      were included. In six studies, peri-implantitis was treated using a non-surgical
      approach (scaling and root planing), whereas in four studies, a surgical approach
      was adopted for treating peri-implantitis. In three studies systemic antibiotics
      were administered and in six studies locally delivered antibiotics were used for
      treatment. One study used the oral route for antibiotic delivery. In three
      studies, minocycline hydrochloride was locally delivered as an adjunctive therapy
      to non-surgical mechanical debridement of infected sites. Nine studies reported
      that traditional peri-implantitis treatment with adjunct antibiotic therapy
      reduces gingival bleeding, suppuration and peri-implant pocket depth. In one
      study, despite surgical debridement of infected sites and systemic antibiotic
      cover, nearly 40% of the implants failed to regain stability. There was no
      placebo or control group in eight out of the nine studies included. CONCLUSION:
      The significance of adjunctive antibiotic therapy in the treatment of peri
      implantitis remains debatable.

PMID- 23879252
TI  - A national audit of Australian dental practice distribution: do all Australians
      get a fair deal?
AB  - Australia is the sixth biggest (by area) country in the world, having a total
      area of about 7.5 million km(2) (3 million square miles). This study located
      every dental practice in the country (private and public) and mapped these
      practices against population. The total population of Australia (21.5 million) is
      distributed across 8,529 suburbs. On average about one-third of the population
      from each State lives in suburbs without practices and 46% live in suburbs with
      one to five dentists. Of those living within the study frameset, 86.6% live
      within 5 km of a private practice and 84.4% live within 10 km of a government
      practice. Australia's dental practices are distributed in a very uneven fashion
      across its vast area. Three-quarters of suburbs have no dental practice and over
      one-third of the population live in these suburbs. This research clearly
      identified that in a vast and uneven socio-geographically distributed country,
      service planning, if left to market forces, will end with a practice distribution
      that is fixed by economic drivers of scale and not that of disease burden. A more
      population health-driven approach to future design and construction of government
      safety net services is needed to address these disparities.

PMID- 23879250
TI  - A dual role of the Wnt signaling pathway during aging in Caenorhabditis elegans.
AB  - Wnt signaling is a major and highly conserved developmental pathway that guides
      many important events during embryonic and larval development. In adulthood,
      misregulation of Wnt signaling has been implicated in tumorigenesis and various
      age-related diseases. These effects occur through highly complicated cell-to-cell
      interactions mediated by multiple Wnt-secreted proteins. While they share a high
      degree of sequence similarity, their function is highly diversified. Although the
      role of Wnt ligands during development is well studied, very little is known
      about the possible actions of Wnt signaling in natural aging. In this study,
      Caenorhabditis elegans serves, for the first time, as a model system to determine
      the role of Wnt ligands in aging. Caenorhabditis elegans has five Wnt proteins,
      mom-2, egl-20, lin-44, cwn-1, and cwn-2. We show that all five Wnt ligands are
      expressed and active past the development stages. The ligand mom-2/Wnt plays a
      major detrimental role in longevity, whereas the function of lin-44/Wnt is
      beneficial for long life. Interestingly, no evidence was found for Wnt signaling
      being involved in cellular or oxidative stress responses during aging. Our
      results suggest that Wnt signaling regulates aging-intrinsic genetic pathways,
      opening a new research direction on the role of Wnt signaling in aging and age
      related diseases. 

PMID- 23879253
TI  - What happens to cavitated primary teeth over time? A 3.5-year prospective cohort
      study in China.
AB  - OBJECTIVES: Data showed that among 5-year-old Chinese, 96.7% of cavitated primary
      teeth were left untreated. The study aimed to report on the course of cavitated
      primary teeth within the Chinese health-care system over a period of 3.5 years.
      METHODS: Selection of high caries risk children for inclusion in a sealant
      comparison study was based on the presence of cavitated dentine lesions in their
      primary teeth. At the 6-month sealant evaluation point many of these cavitated
      dentine lesions had not been treated. This necessitated monitoring these
      cavitated teeth 6-monthly for those exfoliated, restored, with a cavity left
      open, having caused toothache (symptom) and having (or having had) an abscess or
      fistulae (symptom). Care-seeking instruction was given at every evaluation point.
      anova and t-test were used in analysing the data. RESULTS: A total of 1012
      cavitated primary teeth in 305 children (7.6 to 9.3 years old), were followed for
      3.5 years. A total of 92.9% of cavitated primary teeth were left open, while 7.1%
      were restored at some stage during the observation period; 98.5% of restored
      teeth and 95.5% of cavitated teeth left open exfoliated and 93.9% of restored
      teeth and 81.5% of cavitated primary teeth left open exfoliated without any
      symptoms. Having (or having had) toothache was the symptom most frequently
      related to exfoliated restored teeth and to exfoliated cavitated teeth left open.
      Restored primary teeth survived statistically significantly longer than cavitated
      primary teeth left open: 1.99 +/- 0.07 years and 1.68 +/- 0.03 years,
      respectively. CONCLUSION: The large majority of cavitated primary teeth in this
      child population exfoliated without symptoms.

PMID- 23879254
TI  - Gender differences in oral manifestations among HIV-infected Brazilian adults.
AB  - AIM: The purpose of this study was to compare gender differences in the
      prevalence of oral lesions in HIV-infected Brazilian adults. METHODOLOGY: A
      retrospective study was conducted of medical records from HIV/AIDS patients from
      1993 to 2004. Oral lesions were only included in this study if definitively
      diagnosed through microscopic analysis, therapeutic test or according to EC
      Clearing house criteria. RESULTS: A total of 750 men and 237 women were included
      in the study. Statistically significant differences were observed only for oral
      hairy leukoplakia, Kaposi sarcoma and lymphadenopathy (P < 0.01). However, a
      model of logistic regression showed that only oral hairy leukoplakia presented a
      significant association with gender and males had a significantly likelihood
      (four times higher than females) of presenting with this oral manifestation [OR
      4.3 (95% CI: 1.39-13.36)]. CONCLUSION: These data shows that oral manifestations
      are less prevalent in females than in males, particularly oral hairy leukoplakia.

PMID- 23879255
TI  - Compliance of Saudi dental students with infection control guidelines.
AB  - The aim of this study was to investigate compliance of dental students in a Saudi
      dental school with recommended infection control protocols. A pilot-tested
      questionnaire concerning various aspects of infection control practices was
      distributed to 330 dental students. The response rate was 93.9% (n = 311). About
      99% of students recorded the medical history of their patients and 80% were
      vaccinated against hepatitis B. The highest compliance (100%) with recommended
      guidelines was reported for wearing gloves and use of a new saliva ejector for
      each patient. Over 90% of the respondents changed gloves between patients, wore
      face masks, changed hand instruments, burs and handpieces between patients, used
      a rubber dam in restorative procedures and discarded sharp objects in special
      containers. A lower usage rate was reported for changing face masks between
      patients (81%), disinfecting impression materials (87%) and dental prosthesis
      (74%) and wearing gowns (57%). Eye glasses and face shield were used by less than
      one-third of the sample. The majority of students were found to be in compliance
      with most of the investigated infection control measures. Nevertheless, further
      education is needed to improve some infection control measures including
      vaccination for Hepatitis B virus (HBV), wearing eye glasses, gowns and face
      shields and disinfecting impression materials and dental prostheses.

PMID- 23879256
TI  - Socioeconomic and psychosocial correlates of oral health.
AB  - BACKGROUND: It has been proposed that psychosocial variables are important
      determinants of oral health outcomes. In addition, the effect of socioeconomic
      factors in oral health has been argued to work through the shaping of
      psychosocial stressors and resources. This study therefore aimed to examine the
      role of psychosocial factors in oral health after controlling for selected
      socioeconomic and behavioural factors. METHODS: Logistic and generalised linear
      regression analyses were conducted on self-rated oral health, untreated decayed
      teeth and number of decayed, missing and filled teeth (DMFT) from dentate
      participants in a national survey of adult oral health (n = 5364) conducted in
      2004-2006 in Australia. RESULTS: After controlling for all other variables, more
      frequent dental visiting and toothbrushing were associated with poorer self-rated
      oral health, more untreated decay and higher DMFT. Pervasive socioeconomic
      inequalities were demonstrated, with higher income, having a tertiary degree,
      higher self-perceived social standing and not being employed all significantly
      associated with oral health after controlling for the other variables. The only
      psychosocial variables related to self-rated oral health were the stressors
      perceived stress and perceived constraints. Psychosocial resources were not
      statistically associated with self-rated oral health and no psychosocial
      variables were significantly associated with either untreated decayed teeth or
      DMFT after controlling for the other variables. CONCLUSION: Although the role of
      behavioural and socioeconomic variables as determinants of oral health was
      supported, the role of psychosocial variables in oral health outcomes received
      mixed support.

PMID- 23879257
TI  - Topical xylitol administration by parents for the promotion of oral health in
      infants: a caries prevention experiment at a Finnish Public Health Centre.
AB  - OBJECTIVES: This demonstration programme tested topical use of xylitol as a
      possible oral health promoting regimen in infants at a Finnish Public Health
      Centre in 2002-2011. METHODS: Parents (usually mothers) began once- or twice
      daily administration of a 45% solution of xylitol (2.96 m) onto all available
      deciduous teeth of their children at the age of approximately 6-8 months. The
      treatment (xylitol swabbing), which continued till the age of approximately 36
      months (total duration 26-28 months), was carried out using cotton swabs or a
      children's toothbrush; the approximate daily xylitol usage was 13.5 mg per each
      deciduous tooth. RESULTS: At the age of 7 years, caries data on the deciduous
      dentition of 80 children were compared with those obtained from similar,
      untreated children (n = 90). Xylitol swabbing resulted in a significant (P <
      0.001) reduction in the incidence of enamel and dentine caries compared with the
      comparison subjects (relative risk 2.1 and 4.0, respectively; 95% confidence
      intervals 1.42-3.09 and 2.01-7.98, respectively). Similar findings were obtained
      when the children were 5 or 6 years old. The treatment reduced the need of tooth
      filling relative risk and 95% confidence intervals at 7 years: 11.86 and 6.36
      22.10, respectively; P < 0.001). Compared with untreated subjects, the oral
      counts of mutans streptococci were reduced significantly (P < 0.001).
      CONCLUSIONS: Considerable improvement in dental health was accomplished in
      infants participating in a topical at-home xylitol administration experiment,
      which was offered to families in the area by the Public Health Centre as a
      supplement to standard oral health care. Caregiver assessment of the programme
      was mostly rated as high or satisfactory.

PMID- 23879258
TI  - Population genetics of Wolbachia-infected, parthenogenetic and uninfected, sexual
      populations of Tetrastichus coeruleus (Hymenoptera: Eulophidae).
AB  - Wolbachia are endosymbiotic bacteria known to manipulate the reproduction of
      their hosts. These manipulations are expected to have consequences on the
      population genetics of the host, such as heterozygosity levels, genetic diversity
      and gene flow. The parasitoid wasp Tetrastichus coeruleus has populations that
      are infected with parthenogenesis-inducing Wolbachia and populations that are not
      infected. We studied the population genetics of T. coeruleus between and within
      Wolbachia-infected and uninfected populations, using nuclear microsatellites and
      mitochondrial DNA. We expected reduced genetic diversity in both DNA types in
      infected populations. However, migration and gene flow could introduce new DNA
      variants into populations. We therefore paid special attention to individuals
      with unexpected (genetic) characteristics. Based on nuclear and mitochondrial
      DNA, two genetic clusters were evident: a thelytokous cluster containing all
      Wolbachia-infected, parthenogenetic populations and an arrhenotokous cluster
      containing all uninfected, sexual populations. Nuclear and mitochondrial DNA did
      not exhibit concordant patterns of variation, although there was reduced genetic
      diversity in infected populations for both DNA types. Within the thelytokous
      cluster, there was nuclear DNA variation, but no mitochondrial DNA variation.
      This nuclear DNA variation may be explained by occasional sex between infected
      females and males, by horizontal transmission of Wolbachia, and/or by novel
      mutations. Several females from thelytokous populations were uninfected and/or
      heterozygous for microsatellite loci. These unexpected characteristics may be
      explained by migration, by inefficient transmission of Wolbachia, by horizontal
      transmission of Wolbachia, and/or by novel mutations. However, migration has not
      prevented the build-up of considerable genetic differentiation between
      thelytokous and arrhenotokous populations. 

PMID- 23879259
TI  - Gene cloning of porcine adiponectin gene from adipose tissue and construction of
      its eukaryotic expression vector.
AB  - To clone adiponectin (ADPN) gene from Shaziling porcine adipocyte and construct
      its eukaryotic expression vector, total RNA was extracted from subcutaneous fatty
      tissue. One pair of specific primers was designed by Primer 5.0 software
      according to the sequence of ADPN gene of porcine available in GenBank. The ADPN
      gene was amplified by PCR from cDNA and cloned into pMD18-T vector to construct
      recombinant clonal vector pMD-ADPN, sequenced and analysed. A recombinant
      expression plasmid pPICZaA-ADPN was constructed by subcloning the cloned ADPN
      gene into the linearized pPICZaA vector. Then, the plasmid pPICZaA-ADPN was
      expressed in Pichia pastoris (GS115) by electrotransformation. Western blot and
      Bradford analysis were used to determine the target protein induced by methanol.
      Results showed that the genome size of ADPN was 732 bp and encoded 244 amino
      acid, the nucleotide sequence of ADPN shared 100% identity with that of porcine
      available in GenBank. Western blot and Bradford analysis showed that the
      recombinant ADPN was expressed in GS115 correctly and has certain immune
      activity. The expression level of ADPN was 28.5 MUg/ml. In conclusion, the
      recombinant ADPN could express in eukaryotic expression vector pPICZaA-ADPN
      constructed in this study effectively.

PMID- 23879260
TI  - Cloning and characterisation of a putative pollen-specific polygalacturonase gene
      (CpPG1) differentially regulated during pollen development in zucchini (Cucurbita
      pepo L.).
AB  - Studies in zucchini (Cucurbita pepo L. spp. pepo) pollen have been limited to the
      viability and morphology of the mature pollen grain. The enzyme polygalacturonase
      (PG) is involved in pollen development and pollination in many species. In this
      work, we study anther and pollen development of C. pepo and present the cloning
      and characterisation of a putative PG CpPG1 (Accession no. HQ232488) from pollen
      cDNA in C. pepo. The predicted protein for CpPG1 has 416 amino acids, with a high
      homology to other pollen PGs, such as P22 from Oenothera organensis (76%) and
      PGA3 from Arabidopsis thaliana (73%). CpPG1 belongs to clade C, which comprises
      PGs expressed in pollen, and presents a 34 amino acid signal peptide for
      secretion towards the cell wall. DNA-blot analysis revealed that there are at
      least another two genes that code for PGs in C. pepo. The spatial and temporal
      accumulation of CpPG1 was studied by semi-quantitative- and qRT-PCR. In addition,
      mRNA was detected only in anthers, pollen and the rudimentary anthers of bisexual
      flowers (only present in some zucchini cultivars under certain environmental
      conditions that trigger anther development in the third whorl of female flowers).
      However, no expression was detected in cotyledons, stem or fruit. Furthermore,
      CpPG1 mRNA was accumulated throughout anther development, with the highest
      expression found in mature pollen. Similarly, exo-PG activity increased from
      immature anther stages to mature anthers and mature pollen. Overall, these data
      support the pollen specificity of this gene and suggest an involvement of CpPG1
      in pollen development in C. pepo. 

PMID- 23879261
TI  - Acute pharyngitis: low adherence to guidelines highlights need for greater
      flexibility in managing paediatric cases.
AB  - AIM: To describe how physicians manage acute pharyngitis with respect to the
      clinical guidelines. METHODS: The computerized medical records of 105 961
      children in one district of a large health maintenance organization were
      analysed, to identify children aged 0-18 years with a diagnosis of pharyngitis
      and paying their first visit for pharyngitis. Main outcome variables were whether
      a throat culture was performed and the time between their medical consultation
      and purchasing any antibiotics, if at all. RESULTS: A total of 28 511 episodes of
      pharyngitis in 19 865 children aged 0-18, recorded by 125 physicians, were
      analysed (average of 1.4 episodes per child). Throat cultures were performed in
      14 847 episodes (52%), with tests more common among paediatricians and younger
      physicians. Antibiotics were purchased in 24.8% of these cases, without knowing
      the result, and were more commonly associated with male physicians, family
      practitioners, children living in rural areas and drugs bought before the
      weekend. CONCLUSION: About 50% of the physicians did not adhere to the
      guidelines. Factors influencing adherence included physician training, years in
      practice and patients' nonmedical characteristics. It is suggested that the
      existing clinical guidelines should address additional modifiers that will make
      the more applicable in practice.

PMID- 23879262
TI  - New anticancer agents mimicking protein recognition motifs.
AB  - The novel tetrasubstituted pyrrole derivatives 8g, 8h, and 8i showed selective
      cytotoxicity against M14 melanoma cells at low micromolar concentration.
      Structure-activity relationships (SARs) indicated the presence of three aromatic
      substituents on the pyrrole core as necessary for biological activity.
      Computational studies strongly suggest that the peculiar 3D orientation of these
      substituents is able to reproduce the hydrophobic side chains in LxxLL-like
      protein recognition motifs. Biological results showed altered p53 expression and
      nuclear translocation in cells sensitive to the compounds, suggesting p53
      involvement in their anticancer mechanism of action. Unfortunately, because of
      poor solubility of the active analogues, it was not possible to perform further
      investigation by NMR techniques. Pharmacophore models were generated and used to
      perform 3D searches in molecular databases. Results indicated that two compounds
      share the same pharmacological profile and the same pharmacophoric features with
      our new derivatives, and one of them inhibited MDM2-MDM4 heterodimer formation. 

PMID- 23879263
TI  - Essential oil compositions of Alphonsea philastreana (Pierre) Pierre ex Finet &
      Gagnep. and Alphonsea gaudichaudiana (Baill.) Finet & Gagnep. from Vietnam.
AB  - Essential oils isolated from the air-dried leaves of Alphonsea philastreana and
      Alphonsea gaudichaudiana growing in Vietnam have been studied for their
      constituents by means of gas chromatography with flame ionization detector and
      gas chromatography coupled with mass spectrometry. Sesquiterpenes were the most
      prominent class of compound identified in the oils. The quantitatively
      significant constituents of the oils were (E)-beta-ocimene (6.9% and 8.5%),
      bicycloelemene (8.9% and 6.3%), beta-caryophyllene (5.1% and 5.9%), alpha
      humulene (5.8% and 4.6%), bicyclogermacrene (9.3% and 6.3%), guaiol (9.0% and
      5.2%) and alpha-eudesmol (8.3% and 5.5%), respectively, for A. philastreana and
      A. gaudichaudiana. This is the first comprehensive report on the volatile oil
      constituents of the studied species.

PMID- 23879264
TI  - Comparison between alkalimetal and group 11 transition metal halide and hydride
      tetramers: molecular structure and bonding.
AB  - A comparison between alkalimetal (M = Li, Na, K, and Rb) and group 11 transition
      metal (M = Cu, Ag, and Au) (MX)4 tetramers with X = H, F, Cl, Br, and I has been
      carried out by means of the Amsterdam Density Functional software using density
      functional theory at the BP86/QZ4P level of theory and including relativistic
      effects through the ZORA approximation. We have obtained that, in the case of
      alkalimetals, the cubic isomer of Td geometry is more stable than the ring
      structure with D4h symmetry, whereas in the case of group 11 transition metal
      tetramers, the isomer with D4h symmetry (or D2d symmetry) is more stable than the
      Td form. To better understand the results obtained we have made energy
      decomposition analyses of the tetramerization energies. The results show that in
      alkalimetal halide and hydride tetramers, the cubic geometry is the most stable
      because the larger Pauli repulsion energies are compensated by the attractive
      electrostatic and orbital interaction terms. In the case of group 11 transition
      metal tetramers, the D4h/D2d geometry is more stable than the Td one due to the
      reduction of electrostatic stabilization and the dominant effect of the Pauli
      repulsion. 

PMID- 23879265
TI  - Bifacial DNA origami-directed discrete, three-dimensional, anisotropic plasmonic
      nanoarchitectures with tailored optical chirality.
AB  - Discrete three-dimensional (3D) plasmonic nanoarchitectures with well-defined
      spatial configuration and geometry have aroused increasing interest, as new
      optical properties may originate from plasmon resonance coupling within the
      nanoarchitectures. Although spherical building blocks have been successfully
      employed in constructing 3D plasmonic nanoarchitectures because their isotropic
      nature facilitates unoriented localization, it still remains challenging to
      assemble anisotropic building blocks into discrete and rationally tailored 3D
      plasmonic nanoarchitectures. Here we report the first example of discrete 3D
      anisotropic gold nanorod (AuNR) dimer nanoarchitectures formed using bifacial DNA
      origami as a template, in which the 3D spatial configuration is precisely tuned
      by rationally shifting the location of AuNRs on the origami template. A distinct
      plasmonic chiral response was experimentally observed from the discrete 3D AuNR
      dimer nanoarchitectures and appeared in a spatial-configuration-dependent manner.
      This study represents great progress in the fabrication of 3D plasmonic
      nanoarchitectures with tailored optical chirality. 

PMID- 23879266
TI  - Rapid and robust phylotyping of spa t003, a dominant MRSA clone in Luxembourg and
      other European countries.
AB  - BACKGROUND: spa typing is a common genotyping tool for methicillin-resistant
      Staphylococcus aureus (MRSA) in Europe. Given the high prevalence of dominant
      clones, spa-typing is proving to be limited in its ability to distinguish
      outbreak isolates from background isolates. New molecular tools need to be
      employed to improve subtyping of dominant local MRSA strains (e.g., spa type
      t003). METHODS: Phylogenetically critical, or canonical, SNPs (can-SNPs) were
      identified as subtyping targets through sequence analysis of 40 MRSA whole
      genomes from Luxembourg. Real-time PCR assays were designed around target SNPs
      and validated using a repository of 240 previously sub-typed and
      epidemiologically characterized Luxembourg MRSA isolates, including 153 community
      and hospital isolates, 69 isolates from long term care (LTC) facilities, and 21
      prospectively analyzed MRSA isolates. Selected isolates were also analyzed by
      whole genome SNP typing (WGST) for comparison to the SNP assays and other
      subtyping techniques. RESULTS: Fourteen real-time PCR assays were developed and
      validated, including two assays to determine presence of spa t003 or t008. The
      other twelve assays successfully provided a high degree of resolution within the
      t003 subtype. WGST analysis of the LTC facility isolates provided greater
      resolution than other subtyping tools, identifying clusters indicative of ongoing
      transmission within LTC facilities. CONCLUSIONS: canSNP-based PCR assays are
      useful for local level MRSA phylotyping, especially in the presence of one or
      more dominant clones. The assays designed here can be easily adapted for
      investigating t003 MRSA strains in other regions in Western Europe. WGST provides
      substantially better resolution than other typing methods.

PMID- 23879267
TI  - Biological therapies: a long way on from Jenner.

PMID- 23879268
TI  - Training of affect recognition in schizophrenia patients with violent offences:
      behavioral treatment effects and electrophysiological correlates.
AB  - Violent offenders with schizophrenia have a particularly poor performance level
      in facial affect recognition. Nineteen male schizophrenia patients, who had been
      committed to psychiatric hospital detention because of violent offences and lack
      of criminal responsibility, were recruited to receive the Training of Affect
      Recognition (TAR). Performance in the Pictures of Facial Affect (PFA)-test and
      event-related potentials (ERPs) were registered in a pre-post-treatment design.
      TAR was feasible with a very high treatment effect (Cohen's d = 1.88), which
      persisted for 2 months post-treatment. ERPs remained unchanged post- vs. pre
      treatment, while low resolution brain electromagnetic tomography (LORETA)
      revealed activation decreases in left-hemispheric parietal-temporal-occipital
      regions at 172 msec and activation increases in right dorsolateral prefrontal
      cortex and anterior cingulate at 250 msec. Possibly, violent offenders with
      schizophrenia are particularly amenable to TAR because of a high level of
      dysfunction at baseline. Post- vs. pre-treatment changes of neural activity
      (LORETA) may mirror a gain of efficiency in structural face decoding and a shift
      towards a more reflective mode of emotional face decoding, relying on increased
      frontal brain activity. Functional magnetic resonance imaging (BOLD-fMRI) -data
      from another study further supports this notion. TAR treatment might enable
      subjects with schizophrenia and a disposition to violence to reach a higher
      degree of deliberation of their reactive behavior to facial affect stimuli.

PMID- 23879269
TI  - Phosphoproteomics study on the activated PKCdelta-induced cell death.
AB  - The proteolytic activation of protein kinase Cdelta (PKCdelta) generates a
      catalytic fragment called PKCdelta-CF, which induces cell death. However, the
      mechanisms underlying PKCdelta-CF-mediated cell death are largely unknown. On the
      basis of an engineering leukemic cell line with inducible expression of PKCdelta
      CF, here we employ SILAC-based quantitative phosphoproteomics to systematically
      and dynamically investigate the overall phosphorylation events during cell death
      triggered by PKCdelta-CF expression. Totally, 3000 phosphorylation sites were
      analyzed. Considering the fact that early responses to PKCdelta-CF expression
      initiate cell death, we sought to identify pathways possibly related directly
      with PKCdelta by further analyzing the data set of phosphorylation events that
      occur in the initiation stage of cell death. Interacting analysis of this data
      set indicates that PKCdelta-CF triggers complicated networks to initiate cell
      death, and motif analysis and biochemistry verification reveal that several
      kinases in the downstream of PKCdelta conduct these networks. By analysis of the
      specific sequence motif of kinase-substrate, we also find 59 candidate substrates
      of PKCdelta from the up-regulated phosphopeptides, of which 12 were randomly
      selected for in vitro kinase assay and 9 were consequently verified as substrates
      of PKCdelta. To our greatest understanding, this study provides the most
      systematic analysis of phosphorylation events initiated by the cleaved activated
      PKCdelta, which would vastly extend the profound understanding of PKCdelta
      directed signal pathways in cell death. The MS data have been deposited to the
      ProteomeXchange with identifier PXD000225. 

PMID- 23879270
TI  - The year of 2012 in electrocardiology.

PMID- 23879271
TI  - Value of electro-vectorcardiogram in hypertrophic cardiomyopathy.
AB  - The electrocardiogram is an important tool for the initial diagnostic suspicion
      of hypertrophic cardiomyopathy in any of its forms, both in symptomatic and in
      asymptomatic patients because it is altered in more than 90 percent of the cases.
      Electrocardiographic anomalies are more common in patients carriers of manifest
      hypertrophic cardiomyopathy and the electrocardiogram alterations are earlier and
      more sensitive than the increase in left ventricular wall thickness detected by
      the echocardiogram. Nevertheless, despite being the leading cause of sudden death
      among young competitive athletes there is no consensus over the need to include
      the method in the pre-participation screening. In apical hypertrophic
      cardiomyopathy the electrocardiographic hallmarks are the giant negative T waves
      in anterior precordial leads. In the vectorcardiogram, the QRS loop is located
      predominantly in the left anterior quadrant and T loop in the opposite right
      posterior quadrant, which justifies the deeply negative T waves recorded. The
      method allows estimating the left ventricular mass because it relates to the
      maximal spatial vector voltage of the left ventricle in the QRS loop. The
      recording on electrocardiogram or Holter monitoring of nonsustained monomorphic
      ventricular tachycardia in patients with syncope, recurrent syncope in young
      patient, hypotension induced by strain, bradyarrhythmia, or concealed conduction
      are markers of poor prognosis. The presence of rare sustained ventricular
      tachycardia is observed in mid-septal obstructive HCM with apical aneurysm. The
      presence of complete right bundle branch block pattern is frequent after the
      percutaneous treatment and complete left bundle branch block is the rule after
      myectomy. 

PMID- 23879272
TI  - Prevalence and prognostic value of conduction disturbances at the time of
      diagnosis of cardiac AL amyloidosis.
AB  - BACKGROUND AND PURPOSE: To evaluate the prevalence and the prognostic
      implications of conduction delays in a large cohort of cardiac AL patients.
      METHODS: Echo Doppler and 12-lead ECG were collected in 344 consecutive patients
      in whom diagnosis of AL amyloidosis was concluded between 2008 and 2010. Patients
      were subdivided according to the presence (n = 240) or absence (n = 104) of
      cardiac involvement. RESULTS: When compared with patients without myocardial
      involvement, cardiac AL was associated with prolonged PQ, QRS, QT and QTc
      intervals (P < 0.05), and with higher prevalence of intraventricular blocks
      (27.5% vs. 16.5%, P < 0.05), that was associated with higher wall thickness,
      worse diastolic and regional systolic function, higher NT-proBNP values (all P <
      0.05), and higher mortality (P = 0.0001; median follow-up: 402 days). CONCLUSION:
      Intraventricular conduction delays have a negative prognostic impact in patients
      with cardiac AL amyloidosis. Their presence should not be overlooked in the
      diagnostic workup, prompting a more accurate cardiological support.

PMID- 23879273
TI  - The ventriculophasic response: relationship to sinus arrhythmia and the duration
      of interposed QRS complexes.
AB  - BACKGROUND: The ventriculophasic response (VR) refers to shortening of sinus
      cycle length during heart block when a QRS complex is interposed between 2 P
      waves. Our purpose was to analyze its relationship to respiratory sinus
      arrhythmia (SA) and to compare VR in relation to paced versus intrinsic QRS
      complexes. METHODS: Patients with advanced heart block had their pacer devices
      temporarily programmed to ventricular inhibited mode at 30 ppm. In 35 subjects,
      we analyzed VR and SA before, during and after 3 cycles of deep breathing. In 16
      other patients we compared VR in the presence of paced versus narrower intrinsic
      QRS complexes. RESULTS: The magnitude of P-P interval shortening surrounding QRS
      complexes during inspiration correlated with SA (r = 0.36, P = 0.03). The
      prevalence of VR increased from 37% at baseline to 77% of subjects during deep
      breathing (P = 0.02). The mean P-P interval shortening was greater surrounding
      intrinsic QRS complexes than paced QRS complexes (3.6 +/- 3.6% vs. 1.4 +/- 1.1%,
      P = 0.02). The prevalence of VR increased from 25% during paced rhythm to 56%
      when intrinsic complexes were present. CONCLUSION: VR, like SA, increases with
      deep breathing and likely reflects intact parasympathetic nervous system
      function. Its increase in the presence of narrower beats suggests it may reflect
      ventricular synchrony.

PMID- 23879274
TI  - Tpeak -tend interval in 12-lead electrocardiogram of healthy children and
      adolescents tpeak -tend interval in childhood.
AB  - BACKGROUND: Tpeak (Tp) to the Tend (Te) interval is an index of transmural
      dispersion of repolarization. Prolongation of this interval predisposes to life
      threatening ventricular arrhythmias in long QT syndrome, polymorphic
      catecholaminergic ventricular tachycardia, Brugada syndrome and short QT syndrome
      and may be an indicator of increased risk of sudden cardiac death. Very little is
      known about TpTe interval in children and adolescents. METHODS: In 131 healthy
      children (64 girls) aged from 2.3 to 18.5 years (mean 9.1 years) the RR, QT, JT
      and TpTe intervals were measured manually in all leads of resting
      electrocardiogram (ECG). The statistical analysis were performed. RESULTS: TpTe
      intervals vary significantly (P < 0.0001) between individual leads-the longest
      were in lead V3 , the shortest ones in leads III and V1 . Boys had longer TpTe
      intervals, with statistically significant differences in leads I, aVR and
      precordial V2 -V6 . Greater values were also observed in older children. TpTe
      dispersion varied from 6 to 80 ms (mean 38.6 ms +/- 14.6 ms, median 40 ms) with
      no gender differences and greater values in older subjects (P = 0.003). In most
      leads, higher TpTe/QT and TpTe/JT ratios were seen in boys regardless of age. The
      TpTe intervals lengthens with lowering heart rate. CONCLUSIONS: In healthy
      children and adolescents, TpTe intervals vary between individual leads of ECG,
      with the longest in lead V3 . The TpTe interval is longer in boys and in older
      children and prolongs as heart rate decelerates. TpTe/QT and TpTe/JT ratios are
      higher in boys. TpTe interval should be measured in precordial leads.

PMID- 23879275
TI  - The amplitude of fibrillatory waves on leads aVF and V1 predicting the recurrence
      of persistent atrial fibrillation patients who underwent catheter ablation.
AB  - OBJECTIVE: To evaluate whether the amplitude of fibrillatory wave (F wave) on
      electrocardiography could predict the recurrence in persistent atrial
      fibrillation (AF) patients who underwent catheter ablation. METHODS: All
      consecutive persistent AF patients who underwent catheter ablation at Peking
      Union Medical College Hospital between November 2006 and February 2012, were
      enrolled. The amplitude of F wave was measured on three orthogonal leads (leads
      I, V1 and aVF) on the Prucka CardioLab recording system. The primary end point
      was the recurrence after catheter ablation. RESULTS: A total of 54 persistent AF
      patients were enrolled. Fifty patients (age: 58 +/- 11years, 72% male)
      constituted the study population after excluding four patients lost of follow-up.
      The duration of AF was 9 +/- 7 (2-18) months. Twenty-four patients (48%) recurred
      during the follow-up of 25 +/- 19 months, constituted recurrence group. The
      remaining 26 patients constituted control group. The F-wave amplitude in
      recurrence group was significantly lower than control group (lead aVF, 0.085 +/-
      0.018 vs. 0.111 +/- 0.036mV, P = 0.002; lead V1 , 0.116 +/- 0.031 vs. 0.148 +/-
      0.047mV, P = 0.008). The amplitudes of leads aVF (P = 0.023) and V1 (P = 0.031)
      were the independent predictors of AF recurrence. The sensitivity and specificity
      of F-wave amplitude of lead aVF < 0.093mV or V1 < 0.123mV to predict the
      recurrence were 75% and 73%, 68% and 64%, respectively. CONCLUSION: The low
      amplitudes of F wave in leads aVF and V1 could predict the recurrence of patients
      with persistent AF who underwent catheter ablation.

PMID- 23879276
TI  - T-wave alternans and ST depression assessment identifies low risk individuals
      with ischemic cardiomyopathy in the absence of left ventricular hypertrophy.
AB  - BACKGROUND: Although ECG left ventricular hypertrophy (LVH) by Cornell product
      (CP) predicts increased mortality in patients with ischemic cardiomyopathy (ICM),
      those without CP LVH remain at relatively high risk. We examined whether T-wave
      alternans (TWA) testing and ST depression can improve risk stratification in
      these patients. METHODS AND RESULTS: This study examined 317 patients with ICM,
      nonsustained ventricular tachycardia, and a resting ECG in sinus rhythm, who
      presented for electrophysiology and TWA testing, and potential implantable
      cardioverter defibrillator (ICD) implantation. LVH was defined by CP :[(RaVL +
      SV3 ) +6 mm in women] * QRS duration > 2440 mm * msec. ST depression was examined
      as a categorical variable using an established threshold of depression of >=50
      MUV in V5 or V6 . In Cox multivariate models, abnormal TWA testing and ST
      depression were independent predictors of mortality in patients without CP LVH
      (HR 2.52, CI 1.09-5.80, P = 0.030 and HR 2.87, CI 1.41-5.81, P = 0.004,
      respectively). Individuals with no LVH by CP, normal TWA, and no significant ST
      depression, comprised 23% of the study population and had a 5.6% 3-year
      mortality, compared to an overall 20% mortality. CONCLUSIONS: TWA and ST
      depression testing are strong predictors of mortality among ICM patients without
      CP LVH, with normal testing conversely predicting low 3-year mortality. Thus,
      risk assessment with TWA testing and a resting ECG can identify ICM patients at
      low risk who may be less likely to benefit from ICD implantation.

PMID- 23879277
TI  - Potential prevention of pacing-induced heart failure using simple pacemaker
      programming algorithm.
AB  - INTRODUCTION: Right ventricular pacing (RVP) causes ventricular desynchronization
      and may lead to the development of heart failure (HF). Prolongation of
      atrioventricular delay (AVD) in DDDR pacemakers reduces unnecessary RV
      stimulation. The aim of the study was to verify the influence of RVP reduction on
      HF symptoms. METHODS: The study comprised 31 patients (17 men, mean age: 71.6 +/-
      8 yrs) with DDDR pacemaker implanted due to sinus node dysfunction (SND). At
      baseline, 28 patients did not present any symptoms of HF. Three patients were in
      NYHA class II. Patients were randomized either to 150 ms AVD or to minimizing
      right ventricular pacing (MRVP). Crossing over to the alternate mode took place
      after 4 months. Cardiopulmonary exercise test (CPX), echocardiography (ECHO) and
      BNP measurements were done before pacemaker implantation, after 4 and 8 months.
      RESULTS: The percentage of RVP was significantly higher in 150 ms AVD than in
      MRVP: 81.7 +/- 22.6 versus 14.2+/-20.5%, P < 0.0001. Patients with 150 ms mode
      had worse CPX parameters than those with MRVP mode: peak oxygen uptake was 14.2+/
      4.3 versus 19.9+/-6.3 ml/kg per min, P = 0.0001, higher BNP concentrations:
      72.3+/-48.3 versus 49.4+/-43.9 pg/ml, P = 0.001 and worse left ventricle [LV]
      function: ejection fraction: 53.2+/-6.7 versus 57.3+/-5.5%, P < 0.0001; LV
      diastolic diameter: 4.86+/-0.52 versus 4.66+/-0.5 cm, P < 0.01. CONCLUSION:
      Predominant RVP in patients without symptoms of HF at baseline may be responsible
      for worse performance in cardiopulmonary exercise test, higher BNP concentrations
      and impairment of LV function. Specific DDDR pacemaker programming promotes
      intrinsic AV conduction and may prevent the development of pacing-induced HF.

PMID- 23879278
TI  - Evaluation of the Charlson comorbidity index to predict early mortality in
      implantable cardioverter defibrillator patients.
AB  - BACKGROUND: Current guidelines consider the implantation of an implantable
      cardioverter defibrillator (ICD) a class III indication in patients with a life
      expectancy of <1 year. An evaluation of concomitant noncardiac conditions may
      identify patients whom may not derive benefit with ICD therapy. We sought to
      evaluate the association of the Charlson comorbidity index (CCI) on the
      prediction of early mortality (EM), death <1 year after ICD implant. METHODS: The
      study population consisted of patients (n = 1062) undergoing ICD implantation for
      the primary or secondary prevention of sudden cardiac death from 1997 to 2007.
      The predictive value of the CCI on the risk of EM and appropriate shock therapy
      for ventricular arrhythmias as compared to patients without EM after ICD implant
      was calculated using multivariable Cox proportional hazards and receiver operator
      analyses. RESULTS: Patients experiencing EM (n = 110) demonstrated higher CCI
      scores (mean 2.8 +/- 1.3 vs 1.5 +/- 1.2, P < 0.001) as compared to individuals
      without EM (n = 963). Among patients with a CCI of 0, 1, 2, 3, 4, and >=5, the
      incidence of EM increased from 5% to 78%. The CCI was an independent predictor of
      EM (AHR 1.4 [95% CI 1.2-1.6], P < 0.001, per single score increase). Patients who
      experienced EM demonstrated a decreased incidence of appropriate ICD therapy when
      compared to patients without EM (AHR 0.4 [95% CI 0.2-0.7], P = 0.001).
      CONCLUSION: Noncardiac conditions are commonly observed among patients undergoing
      ICD implantation. Guidelines must incorporate a comprehensive assessment of
      concomitant comorbidities to minimize the risk of EM and to maximize the survival
      benefit with ICD therapy.

PMID- 23879279
TI  - Oral contraceptive use and the ECG: evidence of an adverse QT effect on corrected
      QT interval.
AB  - BACKGROUND: A prolonged corrected QT (QTc) interval is a marker for an increased
      risk of sudden cardiac death. We evaluated the relationship between oral
      contraceptive (OC) use, type of OC, and QTc interval. METHODS: We identified
      410,782 ECGs performed at Northern California Kaiser Permanente on female
      patients between 15 and 53 years from January, 1995 to June, 2008. QT was
      corrected for heart rate using log-linear regression. OC generation (first,
      second and third) was classified by increasing progestin androgenic potency,
      while the fourth generation was classified as antiandrogenic. RESULTS: Among
      410,782 women, 8.4% were on OC. In multivariate analysis after correction for
      comorbidities, there was an independent shortening effect of OCs overall (slope =
      -0.5 ms; SE = 0.12, P < 0.0002). Users of first and second generation progestins
      had a significantly shorter QTc than nonusers (P < 0.0001), while users of fourth
      generation had a significantly longer QTc than nonusers (slope = 3.6 ms, SE =
      0.35, P < 0.0001). CONCLUSION: Overall, OC use has a shortening effect on the
      QTc. Shorter QTc is seen with first and second generation OC while fourth
      generation OC use has a lengthening effect on the QTc. Careful examination of
      adverse event rates in fourth generation OC users is needed.

PMID- 23879280
TI  - Gene-specific effect of beta-adrenergic blockade on corrected QT interval in the
      long QT syndrome.
AB  - BACKGROUND: In the long QT syndrome (LQTS) the effects of beta-blocker treatment
      on prevention of cardiac events differs according to the genotype. We aimed to
      assess the effect of beta-blocker treatment on QT/QTc duration in Type 1 LQTS
      (LQT1) and Type 2 LQTS (LQT2) patients. METHODS: 24-hour digital Holter ECG were
      recorded before and after beta-blocking therapy initiation in LQT1 (n = 30) and
      LQT2 patients (n = 16). QT duration was measured on consecutive 1-minute averaged
      QRS-T complexes leading to up to 1440 edited QT-RR pairs for each recording. We
      computed subject- and treatment-specific log/log QT/RR relationships which were
      used to correct the QT intervals. The QT duration was also evaluated at
      predefined heart rates and after correction using Bazett and Fridericia
      coefficients. RESULTS: At baseline, individual QT/RR coefficients were higher in
      LQT2 than in LQT1 patients (0.53 +/- 0.10 vs. 0.40 +/- 0.11, P < 0.001) and
      QT1000 was longer in LQT2 than in LQT1 patients (521 +/- 38 vs. 481 +/- 39 ms, P
      < 0.01). Beta-blockers significantly prolonged the mean RR interval (from 827 +/-
      161 to 939 +/- 197 ms, P < 0.0001). The individual QT/RR coefficients were not
      significantly modified by beta-blockers. Beta-blocker treatment was associated
      with a prolongation of the QT1000 interval (from 481 +/- 39 to 498 +/- 43 ms, P <
      0.01) in LQT1 patients but with a shortening in LQT2 patients (from 521 +/- 38 to
      503 +/- 32 ms, P < 0.01). CONCLUSIONS: The effect of beta-adrenergic blockade on
      QTc duration is different in LQT1 and LQT2 patients. Our data suggest that, in
      LQT1 patients, the well-known positive effect of beta-blockade might be
      associated with a prolongation of QTc duration. The mechanisms of beta-blockade
      protection may be different in LQT1 and in LQT2 patients.

PMID- 23879281
TI  - Diffuse inverted T waves in a young man with structurally normal heart: a case
      report.
AB  - We discuss a young man with episodes of chest pain and dyspnea accompanied with
      transient T-wave inversion in precordial and inferior leads that repeated several
      times. Cardiovascular evaluation did not disclose any structural abnormality.
      Memory T wave following episodes of idiopathic left septal ventricular
      tachycardia was the reason of these changes and did not repeat after arrhythmia
      ablation. 

PMID- 23879283
TI  - Statement of retraction.

PMID- 23879282
TI  - Ventricular fibrillation complicating endomyocardial biopsy of transplanted
      heart.
AB  - Life-threatening arrhythmia is an unusual complication of endomyocardial biopsy
      in transplanted heart. Herein we described a case of VF during endomyocardial
      biopsy. The possibility of VF during a biopsy necessitates immediate access to
      defibrillation during endomyocardial biopsy. 

PMID- 23879288
TI  - Direct imaging of charged impurity density in common graphene substrates.
AB  - Kelvin probe microscopy in ultrahigh vacuum is used to image the local
      electrostatic potential fluctuations above hexagonal boron nitride (h-BN) and
      SiO2, common substrates for graphene. Results are compared to a model of randomly
      distributed charges in a two-dimensional (2D) plane. For SiO2, the results are
      well modeled by 2D charge densities ranging from 0.24 to 2.7 * 10(11) cm(-2),
      while h-BN displays potential fluctuations 1-2 orders of magnitude lower than
      SiO2, consistent with the improvement in charge carrier mobility for graphene on
      h-BN compared to SiO2. Electron beam exposure of SiO2 increases the charge
      density fluctuations, creating long-lived metastable charge populations of ~2 *
      10(11) cm(-2) at room temperature, which can be reversed by heating.

PMID- 23879291
TI  - Communication on the dangers and abuse of skin lighteners in Africa.

PMID- 23879290
TI  - Genotoxicity-related chemistry of human metabolites of benzo[ghi]perylene
      (B[ghi]P) investigated using electro-optical arrays and DNA/microsome biocolloid
      reactors with LC-MS/MS.
AB  - There is limited and sometimes contradictory information about the genotoxicity
      of the polycyclic aromatic hydrocarbon benzo[ghi]perylene (B[ghi]P). Using
      recently developed metabolic toxicity screening arrays and a biocolloid reactor
      LC-MS/MS approach, both featuring films of DNA and human metabolic enzymes, we
      demonstrated the relatively low reactivity of metabolically activated B[ghi]P
      toward DNA. Electro-optical toxicity screening arrays showed that B[ghi]P
      metabolites damage DNA at a 3-fold lower rate than benzo[a]pyrene (B[a]P), whose
      metabolites have a strong and well-understood propensity for DNA damage.
      Metabolic studies using magnetic bead biocolloid reactors coated with microsomal
      enzymes in 96-well plates showed that cyt P450s 1A1 and 1B1 provide high activity
      for B[ghi]P and B[a]P conversion. Consistent with published results, the major
      metabolism of B[ghi]P involved oxidations at 3,4 and 11,12 positions, leading to
      the formation of B[ghi]P 3,4-oxide and B[ghi]P 3,4,11,12-bisoxide. B[ghi]P 3,4
      oxide was synthesized and reacted with deoxyadenosine at N6 and N7 positions and
      with deoxyguanosine at the N2 position. B[ghi]P 3,4-oxide is hydrolytically
      unstable and transforms into the 3,4-diol or converts to 3- or 4-hydroxy B[ghi]P.
      LC-MS/MS of reaction products from the magnetic biocolloid reactor particles
      coated with DNA and human enzymes revealed for the first time that a major DNA
      adduct results from the reaction between B[ghi]P 3,4,11,12-bisoxide and
      deoxyguanosine. Results also demonstrated 5-fold lower formation rates of the
      major DNA adduct for B[ghi]P metabolites compared to B[a]P. Overall, results from
      both the electro-optical array and biocolloid reactor-LC-MS/MS consistently
      suggest a lower human genotoxicity profile of B[ghi]P than B[a]P. 

PMID- 23879292
TI  - Pseudoexfoliation and Alzheimer's disease: a population-based 30-year follow-up
      study.
AB  - PURPOSE:   To determine the effect of pseudoexfoliation (PEX) on the development
      of Alzheimer's disease (AD) in a population in which PEX is a common finding. The
      relationship between open-angle glaucoma (OAG) and AD was also studied. METHODS: 
      Predictors of incident AD, including mixed and unspecified dementia, were
      analysed in a cohort of 679 residents 65-74 years of age, examined in a
      population survey in the municipality of Tierp, Sweden, 1984-1986. To expand the
      cohort, participants in other studies in Tierp were enrolled. In this way, the
      cohort embraced 1123 people, representing more than 15,700 person-years at risk.
      Medical records were reviewed to identify subjects diagnosed with dementia. Those
      with a follow-up time shorter than 2 years were excluded from the study. RESULTS:
      By the conclusion of the study, in December 2011, 174 new cases of AD,
      including mixed and unspecified dementia, had been detected, 41 of whom were
      affected by PEX at baseline. Higher age and female gender were the only
      predictors identified. No association between PEX and AD was found (hazard ratio
      0.98; 95% confidence interval 0.69-1.40). Newly diagnosed OAG at baseline did not
      increase the risk (hazard ratio 1.09; 95% confidence interval 0.69-1.74).
      CONCLUSION:   Pseudoexfoliation is not a predictor of AD. No association was
      found between OAG and AD.

PMID- 23879289
TI  - Emerging roles of the nucleolus in regulating the DNA damage response: the
      noncanonical DNA repair enzyme APE1/Ref-1 as a paradigmatical example.
AB  - SIGNIFICANCE: An emerging concept in DNA repair mechanisms is the evidence that
      some key enzymes, besides their role in the maintenance of genome stability,
      display also unexpected noncanonical functions associated with RNA metabolism in
      specific subcellular districts (e.g., nucleoli). During the evolution of these
      key enzymes, the acquisition of unfolded domains significantly amplified the
      possibility to interact with different partners and substrates, possibly
      explaining their phylogenetic gain of functions. RECENT ADVANCES: After nucleolar
      stress or DNA damage, many DNA repair proteins can freely relocalize from
      nucleoli to the nucleoplasm. This process may represent a surveillance mechanism
      to monitor the synthesis and correct assembly of ribosomal units affecting cell
      cycle progression or inducing p53-mediated apoptosis or senescence. CRITICAL
      ISSUES: A paradigm for this kind of regulation is represented by some enzymes of
      the DNA base excision repair (BER) pathway, such as apurinic/apyrimidinic
      endonuclease 1 (APE1). In this review, the role of the nucleolus and the
      noncanonical functions of the APE1 protein are discussed in light of their
      possible implications in human pathologies. FUTURE DIRECTIONS: A productive cross
      talk between DNA repair enzymes and proteins involved in RNA metabolism seems
      reasonable as the nucleolus is emerging as a dynamic functional hub that
      coordinates cell growth arrest and DNA repair mechanisms. These findings will
      drive further analyses on other BER proteins and might imply that nucleic acid
      processing enzymes are more versatile than originally thought having evolved DNA
      targeted functions after a previous life in the early RNA world.

PMID- 23879293
TI  - Age estimation based on pulp cavity to tooth volume ratio using postmortem
      computed tomography images.
AB  - Pulp cavity size is known to decrease with age and can therefore serve as an
      indicator for age estimation. Here, we evaluated whether reconstructed images of
      multidetector-row computed tomography (MDCT) acquired before forensic autopsy are
      useful for estimating age at death. Images of 136 mandibular first premolars
      obtained from bodies of known age at death were analyzed, and the volume of the
      regions corresponding to pulp cavity and that of the whole tooth were determined
      using a voxel counting function. The pulp cavity was clearly distinguishable from
      dental hard tissue on the reconstructed images when using a cutoff value of 1400
      Hounsfield units. Regression analysis adjusted for sex showed that estimated age
      correlated significantly with the pulp cavity to tooth volume ratio (r = 0.76).
      MDCT is gaining more widespread use in forensic medicine, and analyzing dental
      images to obtain parameters for age prediction is a practical approach for
      postmortem identification.

PMID- 23879294
TI  - Whole body, regional fat accumulation, and appetite-related hormonal response
      after hypoxic training.
AB  - The present study was conducted to determine change in regional fat accumulation
      and appetite-related hormonal response following hypoxic training. Twenty
      sedentary subjects underwent hypoxic (n = 9, HYPO, FiO(2) = 15%) or normoxic
      training (n = 11, NOR, FiO(2) = 20.9%) during a 4-week period (3 days per week).
      They performed a 4-week training at 55% of maximal oxygen uptake (V.O(2max)) for
      each condition. Before and after the training period, V.O(2max), whole body fat
      mass, abdominal fat area, intramyocellular lipid content (IMCL), fasting and
      postprandial appetite-related hormonal responses were determined. Both groups
      showed a significant increase in V.O(2max) following training (P<0.05). Whole
      body and segmental fat mass, abdominal fat area, IMCL did not change in either
      group. Fasting glucose and insulin concentrations significantly reduced in both
      groups (P<0.05). Although area under the curve for the postprandial blood glucose
      concentrations significantly decreased in both groups (P<0.05), the change was
      significantly greater in the HYPO group than in the NOR group (P<0.05). Changes
      in postprandial plasma ghrelin were similar in both groups. A significant
      reduction of postprandial leptin response was observed in both groups (P<0.05),
      while postprandial glucagon-like peptide-1 (GLP-1) concentrations increased
      significantly in the NOR group only (P<0.05). In conclusion, hypoxic training for
      4 weeks resulted in greater improvement in glucose tolerance without loss of
      whole body fat mass, abdominal fat area or IMCL. However, hypoxic training did
      not have synergistic effect on the regulation of appetite-related hormones.

PMID- 23879296
TI  - Measurement of body condition in a common carabid beetle, Poecilus cupreus: a
      comparison of fresh weight, dry weight, and fat content.
AB  - Because of its direct consequences on reproductive success, body condition is an
      often-studied individual trait in insects. Various studies on insects use
      disparate methods to assess "body condition." However, it is doubtful that the
      results obtained by disparate methods are comparable. In this study, the body
      conditions of Poecilus cupreus (Linnaeus) (Coleoptera: Carabidae) from eight
      sites were compared based on the following commonly used variables: (i) fresh
      weight, (ii) dry weight, and (iii) fat content. All of these variables were
      corrected for structural body size. Moreover, the effects of using the following
      ways of assessing structural body size were examined: (a) one size measurement
      (length of elytron, which is commonly used in beetles), and (b) three size
      measurements (length of elytron, width of pronotum and length of hind femur). The
      results obtained using the various estimations of body condition (i, ii, iii)
      varied significantly. Therefore, studies employing distinct body measurements to
      assess body condition are not comparable to each other. Using multiple structural
      size measurements in body condition analyses is better than the common practice
      of using only one size measurement. However, in the present study, results
      provided by both methods differ only slightly. A recommendation on the use of
      terminology in studies on body condition is introduced.

PMID- 23879295
TI  - Spinal muscular atrophy: from gene discovery to clinical trials.
AB  - Spinal muscular atrophy (SMA) is a common neuromuscular disorder with autosomal
      recessive inheritance, resulting in the degeneration of motor neurons. The
      incidence of the disease has been estimated at 1 in 6000-10,000 newborns with a
      carrier frequency of 1 in 40-60. SMA is caused by mutations of the SMN1 gene,
      located on chromosome 5q13. The gene product, survival motor neuron (SMN) plays
      critical roles in a variety of cellular activities. SMN2, a homologue of SMN1, is
      retained in all SMA patients and generates low levels of SMN, but does not
      compensate for the mutated SMN1. Genetic analysis demonstrates the presence of
      homozygous deletion of SMN1 in most patients, and allows screening of
      heterozygous carriers in affected families. Considering high incidence of carrier
      frequency in SMA, population-wide newborn and carrier screening has been
      proposed. Although no effective treatment is currently available, some treatment
      strategies have already been developed based on the molecular pathophysiology of
      this disease. Current treatment strategies can be classified into three major
      groups: SMN2-targeting, SMN1-introduction, and non-SMN targeting. Here, we
      provide a comprehensive and up-to-date review integrating advances in molecular
      pathophysiology and diagnostic testing with therapeutic developments for this
      disease including promising candidates from recent clinical trials. 

PMID- 23879297
TI  - Passive smoking and pain.

PMID- 23879298
TI  - Modest efficacy of voriconazole against murine infections by Sporothrix schenckii
      and lack of efficacy against Sporothrix brasiliensis.
AB  - The efficacy of voriconazole (VRC) was evaluated against two strains of each of
      the two most common species causing sporotrichosis, Sporothrix schenckii sensu
      stricto and Sporothrix brasiliensis, using a murine model of disseminated
      infection. Voriconazole was administered at doses of 20 or 40 mg kg(-1) per day
      by gavage. The drug showed some efficacy, especially at 40 mg kg(-1) per day, in
      prolonging the survival and reducing fungal load in spleen and liver in mice
      infected with S. schenckii, whereas in animals infected with S. brasiliensis the
      drug did not work. 

PMID- 23879299
TI  - Synthesis and evaluation of novel radioligands for positron emission tomography
      imaging of the orexin-2 receptor.
AB  - Orexin receptors (OXRs) in the brain have been implicated in diverse
      physiological and neuropsychiatric conditions. Here we describe the design,
      synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4
      methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyridin-2-yl)-2-(3
      fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission
      tomography (PET) imaging. Structural features were incorporated to increase
      binding affinity for OXRs, to enable carbon-11 radiolabeling, and to adjust
      lipophilicity considered optimal for brain penetration and low nonspecific
      binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat
      brain sections showed that specific binding of [(11)C]9a was distributed
      primarily to neocortical layer VI and hypothalamus, consistent with reported
      localizations of orexin-2 receptors (OX2Rs). In vivo PET study of [(11)C]9a
      demonstrated moderate uptake of radioactivity into rat and monkey brains under
      deficiency or blockade of P-glycoprotein, and distribution of PET signals in the
      brain was in agreement with autoradiographic data. Our approach and findings have
      provided significant information for development of OX2R PET tracers. 

PMID- 23879300
TI  - Contrasting genetic responses to population fragmentation in a coevolving fig and
      fig wasp across a mainland-island archipelago.
AB  - Interacting species of pollinator-host systems, especially the obligate ones, are
      sensitive to habitat fragmentation, due to the nature of mutual dependence.
      Comparative studies of genetic structure can provide insights into how habitat
      fragmentation contributes to patterns of genetic divergence among populations of
      the interacting species. In this study, we used microsatellites to analyse
      genetic variation in Chinese populations of a typical mutualistic system - Ficus
      pumila and its obligate pollinator Wiebesia sp. 1 - in a naturally fragmented
      landscape. The plants and wasps showed discordant patterns of genetic variation
      and geographical divergence. There was no significant positive relationship in
      genetic diversity between the two species. Significant isolation-by-distance
      (IBD) patterns occurred across the populations of F. pumila and Wiebesia sp. 1 as
      whole, and IBD also occurred among island populations of the wasps, but not the
      plants. However, there was no significant positive relationship in genetic
      differentiation between them. The pollinator populations had significantly lower
      genetic variation in small habitat patches than in larger patches, and three
      island pollinator populations showed evidence of a recent bottleneck event. No
      effects of patch size or genetic bottlenecks were evident in the plant
      populations. Collectively, the results indicate that, in more fragmented
      habitats, the pollinators, but not the plants, have experienced reduced genetic
      variation. The contrasting patterns have multiple potential causes, including
      differences in longevity and hence number of generations experiencing
      fragmentation; different dispersal patterns, with the host's genes dispersed as
      seeds as well as a result of pollen dispersal via the pollinator; asymmetrical
      responses to fluctuations in partner populations; and co-existence of a rare
      second pollinating wasp on some islands. These results indicate that strongly
      interdependent species may respond in markedly different ways to habitat
      fragmentation. 

PMID- 23879301
TI  - Modification of the Assessment of Life Habits (LIFE-Hm) to consider personalized
      satisfaction with participation in activities and roles: results from a construct
      validity study with older adults.
AB  - PURPOSE: Participation, defined as a person's involvement in activities and
      roles, is a primary intervention goal in rehabilitation. To achieve client
      centered practice, rehabilitation professionals need to go beyond objective
      accomplishment criteria and consider satisfaction with and the importance of
      participation in activities and roles. To our knowledge, no instrument considers
      accomplishment, satisfaction and importance of activities and roles, and allows
      numerical scoring and comparison. The objectives of this study were to modify the
      Assessment of Life Habits questionnaire (LIFE-Hm) to consider personalized
      satisfaction (satisfaction weighted by importance) with participation in
      activities and roles, and to: (1) examine its convergent validity with quality of
      life (QOL) and (2) compare the associations between QOL on the one hand and,
      satisfaction (LIFE-H) and personalized satisfaction (LIFE-Hm) with participation
      on the other. METHOD: A descriptive cross-sectional study was conducted with 84
      older adults, average age 76 years, with different functional autonomy levels.
      RESULTS: Quality of life was associated with personalized satisfaction for all
      categories of activities and roles (r = 0.45 to 0.75; p < 0.001). These
      associations differed significantly from the associations with satisfaction for
      the "housing", "mobility" and "responsibilities" categories (p = 0.04 to 0.0047).
      CONCLUSIONS: This study found good construct validity of the LIFE-Hm with QOL.
      Personalization can add value in achieving client-centered practice. Implications
      for Rehabilitation The LIFE-Hm becomes the first instrument available in English
      and French that allows comparison between individuals and informs rehabilitation
      professionals about the level of accomplishment, satisfaction and personalized
      satisfaction with participation in activities and roles. Personalized
      satisfaction can add value in achieving client-centered practice as it considers
      not only how satisfying activities and roles are for the person, but also the
      importance that these activities and roles have for her/him. The LIFE-Hm offers
      the advantage of systematically identifying activities and roles which are not
      satisfactory but are important for the client and have the potential to be
      improved (lower accomplishment level).

PMID- 23879302
TI  - Two new non-glycosidic iridoids from Sambucus ebulus.
AB  - Two new 'Valeriana-type' non-glycosidic iridoids were isolated from the aerial
      parts (leaves and young branches) of Sambucus ebulus L., a perennial herbaceous
      species widespread in Europe. The structures were elucidated, by spectroscopic
      means, as 7-O-acetylpatrinoside aglycone (1) and 10-O-acetylpatrinoside aglycone
      (2). 

PMID- 23879303
TI  - Reactive-template fabrication of porous SnO2 nanotubes and their remarkable gas
      sensing performance.
AB  - A facile reactive-template strategy has been developed to fabricate porous SnO2
      nanotubes using MnO2 nanorods as the sacrificial template. The formation of
      nanotubes is based on the redox reaction mechanism, which requires no post
      treatment of the MnO2 templates. The morphological and structural characteristics
      of the samples have been systematically characterized by X-ray powder diffraction
      (XRD), scanning electron microscopy (SEM), transmission electron microscopy
      (TEM), thermal-gravimetric (TG), and N2 adsorption-desorption techniques. A gas
      sensor device was constructed using as-prepared SnO2 nanotubes and was tested for
      its ability to detect ethanol and some other compounds. Because of the porous
      structure and relative large specific surface area, the SnO2 nanotube sensor
      manifests remarkably improved sensing performance, including fast response
      recovery, high sensitivity, and excellent repeatability, suggesting the promising
      application of the SnO2 nanotube materials. 

PMID- 23879304
TI  - Kinetics simulation of luminol chemiluminescence based on quantitative analysis
      of photons generated in electrochemical oxidation.
AB  - The kinetics of electrogenerated chemiluminescence (ECL) of luminol at a gold
      electrode in alkaline solution was investigated by measuring the absolute number
      of photons emitted in an integrating sphere. The ECL efficiency as the ratio of
      photon to electric charge was 0.0004 in cyclic voltammography and 0.0005 in
      chronoamperometry. By numerically solving the rate equations based on a diffusion
      layer model, the observed time profile of the luminescence intensity could be
      successfully simulated from the oxidation current of luminol in the
      chronoamperometry. In the simulation, the rate constant for the oxidation of
      luminol by superoxide radicals in alkaline solution was determined to be 6 *
      10(5) M(-1) s(-1). The present methodology and the achievement could be widely
      applicable to various analytical techniques using chemiluminescence. 

PMID- 23879305
TI  - Addition of host genetic variants in a prediction rule for post meningitis
      hearing loss in childhood: a model updating study.
AB  - BACKGROUND: Sensorineural hearing loss is the most common sequela in survivors of
      bacterial meningitis (BM). In the past we developed a validated prediction model
      to identify children at risk for post-meningitis hearing loss. It is known that
      host genetic variations, besides clinical factors, contribute to severity and
      outcome of BM. In this study it was determined whether host genetic risk factors
      improve the predictive abilities of an existing model regarding hearing loss
      after childhood BM. METHODS: Four hundred and seventy-one Dutch Caucasian
      childhood BM were genotyped for 11 single nucleotide polymorphisms (SNPs) in
      seven different genes involved in pathogen recognition. Genetic data were added
      to the original clinical prediction model and performance of new models was
      compared to the original model by likelihood ratio tests and the area under the
      curve (AUC) of the receiver operating characteristic curves. RESULTS: Addition of
      TLR9-1237 SNPs and the combination of TLR2 + 2477 and TLR4 + 896 SNPs improved
      the clinical prediction model, but not significantly (increase of AUC's from
      0.856 to 0.861 and from 0.856 to 0.875 (p = 0.570 and 0.335, respectively). Other
      SNPs analysed were not linked to hearing loss. CONCLUSIONS: Although addition of
      genetic risk factors did not significantly improve the clinical prediction model
      for post-meningitis hearing loss, AUC's of the pre-existing model remain high
      after addition of genetic factors. Future studies should evaluate whether more
      combinations of SNPs in larger cohorts has an additional value to the existing
      prediction model for post meningitis hearing loss.

PMID- 23879306
TI  - Exploring international clinical education in US-based programs: identifying
      common practices and modifying an existing conceptual model of international
      service-learning.
AB  - BACKGROUND: Increasingly physical therapist students complete part of their
      clinical training outside of their home country. This trend is understudied. The
      purposes of this study were to: (1) explore, in depth, various international
      clinical education (ICE) programs; and (2) determine whether the Conceptual Model
      of Optimal International Service-Learning (ISL) could be applied or adapted to
      represent ICE. METHODS: Qualitative content analysis was used to analyze ICE
      programs and consider modification of an existing ISL conceptual model for ICE.
      Fifteen faculty in the United States currently involved in ICE were interviewed.
      The interview transcriptions were systematically analyzed by two researchers.
      RESULTS: Three models of ICE practices emerged: (1) a traditional clinical
      education model where local clinical instructors (CIs) focus on the development
      of clinical skills; (2) a global health model where US-based CIs provide the
      supervision in the international setting, and learning outcomes emphasized global
      health and cultural competency; and (3) an ICE/ISL hybrid where US-based CIs
      supervise the students, and the foci includes community service. Additionally the
      data supported revising the ISL model's essential core conditions, components and
      consequence for ICE. CONCLUSIONS: The ICE conceptual model may provide a useful
      framework for future ICE program development and research.

PMID- 23879307
TI  - Multimodal physical therapy management of a 48-year-old female with post-stroke
      complex regional pain syndrome.
AB  - This case report describes a 48-year-old female who presented with complaints of
      right shoulder pain, hyperesthesias and swelling of the hand along with added
      symptoms of pain centralization following a cerebrovascular accident. On clinical
      evaluation, the patient satisfied the Budapest diagnostic criteria for Complex
      Regional Pain Syndrome (CRPS) type-1. Physical therapy management (1st three
      sessions) was initially focused on pain neurophysiology education with an aim to
      reduce kinesiophobia and reconceptualise her pain perception. The patient had an
      immediate significant improvement in her pain and functional status. Following
      this, pain modulation in the form of transcutaneous electrical nerve stimulation,
      kinesio tape application, "pain exposure" physical therapy and exercise therapy
      was carried out for a period of 7 weeks. The patient had complete resolution of
      her symptoms which was maintained at a six-month follow-up.

PMID- 23879308
TI  - Removal of waterborne pathogens from liver transplant unit water taps in
      prevention of healthcare-associated infections: a proposal for a cost-effective,
      proactive infection control strategy.
AB  - Hospital water supplies often contain waterborne pathogens, which can become a
      reservoir for healthcare-associated infections (HAIs). We surveyed the extent of
      waterborne pathogen contamination in the water supply of a Liver Transplant Unit.
      The efficacy of point-of-use (POU) water filters was evaluated by comparative
      analysis in routine clinical use. Our baseline environmental surveillance showed
      that Legionella spp. (28%, 38/136), Pseudomonas aeruginosa (8%, 11/136),
      Mycobacterium spp. (87%, 118/136) and filamentous fungi (50%, 68/136) were
      isolated from the tap water of the Liver Transplant Unit. 28.9% of Legionella
      spp.-positive water samples (n = 38) showed high-level Legionella contamination
      (>=10(3) CFU/L). After installation of the POU water filter, none of these
      pathogens were found in the POU filtered water samples. Furthermore,
      colonizations/infections with Gram-negative bacteria determined from patient
      specimens were reduced by 47% during this period, even if only 27% (3/11) of the
      distal sites were installed with POU water filters. In conclusion, the presence
      of waterborne pathogens was common in the water supply of our Liver Transplant
      Unit. POU water filters effectively eradicated these pathogens from the water
      supply. Concomitantly, healthcare-associated colonization/infections declined
      after the POU filters were installed, indicating their potential benefit in
      reducing waterborne HAIs.

PMID- 23879310
TI  - IDPQuantify: combining precursor intensity with spectral counts for protein and
      peptide quantification.
AB  - Differentiating and quantifying protein differences in complex samples produces
      significant challenges in sensitivity and specificity. Label-free quantification
      can draw from two different information sources: precursor intensities and
      spectral counts. Intensities are accurate for calculating protein relative
      abundance, but values are often missing due to peptides that are identified
      sporadically. Spectral counting can reliably reproduce difference lists, but
      differentiating peptides or quantifying all but the most concentrated protein
      changes is usually beyond its abilities. Here we developed new software,
      IDPQuantify, to align multiple replicates using principal component analysis,
      extract accurate precursor intensities from MS data, and combine intensities with
      spectral counts for significant gains in differentiation and quantification. We
      have applied IDPQuantify to three comparative proteomic data sets featuring gold
      standard protein differences spiked in complicated backgrounds. The software is
      able to associate peptides with peaks that are otherwise left unidentified to
      increase the efficiency of protein quantification, especially for low-abundance
      proteins. By combing intensities with spectral counts from IDPicker, it gains an
      average of 30% more true positive differences among top differential proteins.
      IDPQuantify quantifies protein relative abundance accurately in these test data
      sets to produce good correlations between known and measured concentrations. 

PMID- 23879312
TI  - Selective trapping of labile S3 in a porous coordination network and the direct X
      ray observation.
AB  - S3 is one of the basic allotropes of sulfur but is still a mysterious labile
      species. We selectively trapped S3 in a pore of a thermally stable coordination
      network and determined S3 structure by ab initio X-ray powder diffraction
      analysis. S3 in a pore has a C2v bent structure. The network containing trapped
      S3 is remarkably stable under ambient conditions and is inert to
      photoirradiation. S3 in the network could be transformed to S6 by mechanical
      grinding or heating in the presence of NH4X (X = Cl or Br). S6 could be reverse
      transformed to S3 by photoirradiation. We also determined the structure of the
      network containing S6 by ab initio X-ray powder diffraction analysis. 

PMID- 23879311
TI  - Statin use and risk of kidney cancer: a meta-analysis of observational studies
      and randomized trials.
AB  - AIM: Clinical studies have shown that statin use may modify the risk of kidney
      cancer. However, these studies yielded different results. To quantify the
      association between statin use and risk of kidney cancer, we performed a detailed
      meta-analysis of published studies regarding this subject. METHODS: A literature
      search was carried out using MEDLINE, EMBASE and the Cochrane database between
      January 1966 and October 2012. Prior to performing a meta-analysis, the studies
      were evaluated for publication bias and heterogeneity. Fixed effect and random
      effect models were used to estimate summary relative risks (RR) and the
      corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity
      analysis were also performed. RESULTS: A total of 12 (two randomized controlled
      trials, five cohort, and five case-control) studies contributed to the analysis.
      There was heterogeneity among the studies but no evidence of publication bias.
      Pooled results indicated a non-significant decrease of total kidney cancer risk
      among all statin users (RR = 0.92, 95% CI 0.71, 1.19). Long term statin use did
      not significantly affect the risk of total kidney cancer (RR = 1.01, 95% CI 0.83,
      1.22). In our subgroup analyses, the results were not substantially affected by
      study design, confounder adjustment and gender. Furthermore, sensitivity analysis
      confirmed the stability of the results. CONCLUSION: The findings of this meta
      analysis suggested that there was no association between statin use and risk of
      kidney cancer. More studies, especially randomized controlled trials and high
      quality cohort studies with larger sample size and well controlled confounding
      factors, are needed to confirm this association in the future.

PMID- 23879313
TI  - Progression of coronary artery calcification after kidney transplantation.
AB  - Calcification of coronary vessels progresses rapidly in hemodialysis (HD)
      patients and comprises a strong predictor of cardiovascular events. The aim of
      this prospective study was to evaluate the coronary artery calcification (CAC) in
      patients with end stage renal disease undergoing regular HD and to determine the
      effect of renal transplantation (RT) in the progression of CAC, using the
      Agatston technique for calcium scoring. The study included 20 patients with end
      stage renal disease undergoing a regular HD treatment (16 males, 4 females) 54.1
      +/- 9.5 years old who had just received a renal transplant and 16 more HD
      patients (11 males, 5 females) 54.4 +/- 13.8 years old as control group. The
      baseline evaluation showed a very high prevalence of CAC in both groups, which
      was positively correlated with age (p < 0.001) and CRP (p = 0.03). The second
      (follow-up) evaluation showed a significant slower progression of calcification
      after RT. In both groups, high calcium score values in the follow-up evaluation
      had a strong positive correlation with baseline calcium score (p < 0.001).

PMID- 23879314
TI  - Electrical transport measured in atomic carbon chains.
AB  - The first electrical-transport measurements of monatomic carbon chains are
      reported in this study. The chains were obtained by unraveling carbon atoms from
      graphene ribbons while an electrical current flowed through the ribbon and,
      successively, through the chain. The formation of the chains was accompanied by a
      characteristic drop in the electrical conductivity. The conductivity of the
      chains was much lower than previously predicted for ideal chains. First
      principles calculations using both density functional and many-body perturbation
      theory show that strain in the chains has an increasing effect on the
      conductivity as the length of the chains increases. Indeed, carbon chains are
      always under varying nonzero strain that transforms their atomic structure from
      the cumulene to the polyyne configuration, thus inducing a tunable band gap. The
      modified electronic structure and the characteristics of the contact to the
      graphitic periphery explain the low conductivity of the locally constrained
      carbon chain. 

PMID- 23879315
TI  - Stature estimation from foramen magnum region in Chinese population.
AB  - Estimation of stature from body parts plays a vital role in identifying the dead.
      This study focused on dimensions of the foramen magnum region and examined the
      relationship between stature and the dimensions of the foramen magnum region in
      northern and southern Chinese populations. Measurements were taken on the skulls
      of 276 individuals (all male). Data on 48 individuals from northern China and 140
      from southern China were used for further stature reconstruction of the above two
      populations in China. Statistical analyses indicate that bilateral variation is
      insignificant for all measurements except maximum length of condyle in the
      southern Chinese population (p < 0.01) and that the northern and southern
      populations differ significantly only in the minimum distance between condyles.
      Linear and multiple regression equations for stature estimation were established.
      The correlation coefficients between stature and the various measurements
      differed between the northern and southern Chinese populations. 

PMID- 23879316
TI  - Simultaneous occurrence of Sweet's syndrome and erythema nodosum possibly
      associated with sulfasalazine.

PMID- 23879317
TI  - Editorial. Fifth issue of 2013.

PMID- 23879319
TI  - Influence of short-term drought conditions and subsequent re-watering on the
      physiology and proteome of Lolium multiflorum/Festuca arundinacea introgression
      forms, with contrasting levels of tolerance to long-term drought.
AB  - Festuca arundinacea is a drought tolerant species. Lolium multiflorum has better
      forage quality but lower tolerance to abiotic stresses. Their hybrids offer an
      opportunity to perform research on the molecular basis of tolerance to drought.
      The aim of this work was to recognise the mechanisms of response to short-term
      drought (11 days) in a glasshouse in two L. multiflorum/F. arundinacea
      introgression forms with distinct levels of tolerance to long-term drought (14
      weeks) in the field. Measurements of physiological parameters, analyses of
      protein accumulation profiles using two-dimensional gel electrophoresis, and mass
      spectrometry identification of proteins, which were accumulated differentially
      between the selected genotypes during short-term drought, were performed.
      Genotype 7/6, with lower yield potential during 14 weeks of drought, and lower
      ability to re-grow after watering, had a higher capacity for photosynthesis
      during 11 days of drought. Genotype 4/10, more tolerant to long-term drought, was
      able to repair damaged cell membranes after watering and was also characterised
      by lower transpiration during short-term drought. A total of 455 proteins were
      analysed, and the 17 that were differentially accumulated between the two
      genotypes were identified. The results of physiological and proteomic research
      led to a hypothesis that the higher photosynthetic capacity of genotype 7/6 could
      be due to a more efficient Calvin cycle, supported by higher accumulation of
      crucial proteins involving chloroplast aldolase.

PMID- 23879318
TI  - World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for
      biological treatment of unipolar depressive disorders, part 1: update 2013 on the
      acute and continuation treatment of unipolar depressive disorders.
AB  - OBJECTIVES: This 2013 update of the practice guidelines for the biological
      treatment of unipolar depressive disorders was developed by an international Task
      Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The
      goal has been to systematically review all available evidence pertaining to the
      treatment of unipolar depressive disorders, and to produce a series of practice
      recommendations that are clinically and scientifically meaningful based on the
      available evidence. The guidelines are intended for use by all physicians seeing
      and treating patients with these conditions. METHODS: The 2013 update was
      conducted by a systematic update literature search and appraisal. All
      recommendations were approved by the Guidelines Task Force. RESULTS: This first
      part of the guidelines (Part 1) covers disease definition, classification,
      epidemiology, and course of unipolar depressive disorders, as well as the
      management of the acute and continuation phase treatment. It is primarily
      concerned with the biological treatment (including antidepressants, other
      psychopharmacological medications, electroconvulsive therapy, light therapy,
      adjunctive and novel therapeutic strategies) of adults. CONCLUSIONS: To date,
      there is a variety of evidence-based antidepressant treatment options available.
      Nevertheless there is still a substantial proportion of patients not achieving
      full remission. In addition, somatic and psychiatric comorbidities and other
      special circumstances need to be more thoroughly investigated. Therefore, further
      high-quality informative randomized controlled trials are urgently needed.

PMID- 23879320
TI  - Immunoglobulin (Ig)M antibodies against oxidized cardiolipin but not native
      cardiolipin are novel biomarkers in haemodialysis patients, associated negatively
      with mortality.
AB  - The risk of premature death is high in haemodialysis (HD) patients. Antibodies
      against cardiolipin (anti-CL) are thrombogenic in diseases such as systemic lupus
      erythematosus (SLE). CL is easily oxidized (Ox) and plays a role in apoptosis. In
      this work we studied immunoglobulin (Ig)M anti-CL and anti-OxCL in HD-patients.
      We conducted an observational study with a prospective follow-up examining the
      relationship between anti-CL, anti-OxCL and mortality risk in a well
      characterized cohort of 221 prevalent HD patients [56% men, median age 66
      (interquartile range 51-74) years, vintage time 29 (15-58) months] with a mean
      follow-up period of 41 (20-48 months). According to the receiver operator
      characteristic (ROC) analysis, anti-OxCL [area under the curve (AUC) 0.62, P <
      0.01], but not anti-CL (AUC 0.52, P = 0.2), is associated with mortality. In
      crude and adjusted Cox analysis, every log increase in anti-OxCL inversely
      predicted all-cause [adjusted hazard ratios (HR) 0.62 (0.43-0.89)] and CVD
      related [adjusted HR 0.56 (0.32-0.98)] mortality. Patients with anti-OxCL levels
      below median also had increased all-cause and cardiovascular disease (CVD)
      related mortality. Although anti-OxCL and anti-phosphorylcholine (PC) were
      related positively to each other (rho = 0.57, P < 0.01), patients with one or two
      of these autoantibody levels below the median were associated with an
      incrementally increased death risk. Anti-OxCL were co-factor beta2-GPI
      independent; anti-CL from patients with anti-phospholipid antibody syndrome were
      beta2-GPI-dependent, while sera from HD-patients less so. Sera from healthy
      donors was not beta2-GPI-dependent. Anti-OxCL IgM is beta2-glycoprotein 1 (GPI)
      independent and a novel biomarker; low levels are associated with death among HD
      patients (and high levels with decreased risk). Combination with anti-PC
      increases this association. Putative therapeutic implications warrant further
      investigation. 

PMID- 23879321
TI  - The concept of research utilization as understood by Swedish nurses: demarcations
      of instrumental, conceptual, and persuasive research utilization.
AB  - BACKGROUND AND AIMS: The literature implies research utilization (RU) to be a
      multifaceted and complex phenomenon, difficult to trace in clinical practice. A
      deeper understanding of the concept of RU in a nursing context is needed, in
      particular, for the development of instruments for measuring nurses' RU, which
      could facilitate the evaluation of interventions to support the implementation of
      evidence-based practice. In this paper, we explored nurses' demarcation of
      instrumental RU (IRU), conceptual RU (CRU), and persuasive RU (PRU) using an item
      pool proposed to measure IRU, CRU, and PRU. METHODS: The item pool (12 items) was
      presented to two samples: one of practicing registered nurses (n = 890) in Sweden
      4 years after graduating and one of recognized content experts (n = 7).
      Correlation analyses and content validity index (CVI) calculations were used
      together with qualitative content analysis, in a mixed methods design. FINDINGS:
      According to the item and factor analyses, CRU and PRU could not be
      distinguished, whereas IRU could. Analyses also revealed problems in linking the
      CRU items to the external criteria. The CVIs, however, showed excellent or good
      results for the IRU, CRU, and PRU items as well as at the scale level. The
      qualitative data indicated that IRU was the least problematic for the experts to
      categorize, whereas CRU and PRU were harder to demarcate. CONCLUSIONS: Our
      findings illustrate a difficulty in explicitly demarcating between CRU and PRU in
      clinical nursing. We suggest this overlap is related to conceptual incoherence,
      indicating a need for further studies. The findings constitute new knowledge
      about the RU concepts in a clinical nursing context, and highlight differences in
      how the concepts can be understood by RNs in clinical practice and experts within
      the field. We suggest that the findings are useful for defining RU in nursing and
      further development of measures of RU.

PMID- 23879322
TI  - Novel technique of implantation for reversed modified right lobe graft from a
      donor with situs inversus totalis: new challenge in adult living donor liver
      transplantation.

PMID- 23879323
TI  - Clinical results of 40 years of paediatric keratoplasty in a single university
      eye clinic.
AB  - PURPOSE:   To evaluate indications for paediatric keratoplasty in recipients aged
      <=16 years and assess long-term clinical outcome. METHOD:   Recipients were
      identified from records of the Danish Cornea Bank. Data were collected from
      patient journals, clinical follow-up examinations and questionnaires and
      stratified into pre-, peri- and postoperative variables. Diagnoses were
      classified into acquired traumatic, acquired nontraumatic and congenital groups.
      Recipients were divided into groups of <8 and >=8 years. Data were analyzed using
      relative percentages and Kaplan-Meier survival plots. RESULTS:   Thirty-three out
      of sixty identified recipients (73 keratoplasties in 63 eyes) were invited.
      Twenty-four accepted, seven still attended follow-up in our clinic. Follow-up
      data reached 95% of the eligible recipients (median follow-up 11 years). Twenty
      three per cent were <8 years and 77%<=8 years. Diagnoses were mainly acquired
      nontraumatic (69%), acquired traumatic (12%) and congenital (7%). Indications
      were primarily optical (52%) or tectonic (41%). Graft survival was best in the
      acquired nontraumatic group (except regrafts) (median survival 15-20 years) and
      poorest in the regraft subgroup as well as the acquired traumatic and congenital
      groups (median survival 1-2 years). Graft failure was higher in the youngest with
      predisposing risk factors and in combined procedures. In terms of indications,
      visual improvement and eye preservation was achieved in 70%. CONCLUSION:  
      Paediatric keratoplasty was successful regarding indication. Graft survival was
      best in the acquired nontraumatic group and poorest in the congenital group.
      Vascularization and/or combined risk factors, additional surgeries and young
      recipient age influenced negatively on graft survival.

PMID- 23879324
TI  - Identification of anaerobic threshold by analysis of heart rate variability
      during discontinuous dynamic and resistance exercise protocols in healthy older
      men.
AB  - The purposes of this study were to determine anaerobic threshold (AT) during
      discontinuous dynamic and resistive exercise protocols by analysing of heart rate
      variability (HRV) and blood lactate (BL) in healthy elderly subjects and compare
      the cardiovascular, metabolic and autonomic variables obtained from these two
      forms of exercise. Fourteen elderly (70 +/- 4 years) apparently healthy males
      underwent the following tests: (i) incremental ramp test on cycle ergometer, (ii)
      one repetition maximum (1RM) leg press at 45 degrees , (iii) a discontinuous
      exercise test on a cycle ergometer (DET-C) protocol and (iv) a resistance
      exercise leg press (DET-L) protocol. Heart rate, blood pressure and BL were
      obtained during each increment of exercise intensity. No significant differences
      (P>0.05) were found between methods of AT determination (BL and HRV) nor the
      relative intensity corresponding to AT (30% of maximum intensity) between the
      types of exercise (DET-C and DET-L). Furthermore, no significant differences
      (P>0.05) were found between the DET-C and DET-L in relation to HRV, however, the
      DET-L provided higher values of systolic blood pressure and BL (P<0.05) from the
      intensity corresponding to AT. We conclude that HRV was effective in
      determination of AT, and the parasympathetic modulation responses obtained during
      dynamic and resistive exercise protocols were similar when compared at the same
      relative intensity. However, DET-L resulted in higher values of blood pressure
      and BL at workloads beyond AT.

PMID- 23879325
TI  - Secondary transfer effects of intergroup contact via social identity complexity.
AB  - Secondary transfer effects (STEs) of intergroup contact refer to the
      generalization of contact effects from a primary encountered outgroup to
      attitudes towards secondary outgroups (Pettigrew, 2009). Using two large, cross
      sectional data sets from Germany (N = 1,381) and Northern Ireland (N = 1,948),
      this article examined the extent to which STEs of intergroup contact on attitudes
      towards a range of secondary outgroups occur via a previously unexplored
      psychological construct, social identity complexity (operationalized as
      similarity complexity and overlap complexity). Study 1 found primary outgroup
      contact to be associated with greater similarity complexity, but no indirect
      effects on secondary outgroup attitudes via complexity emerged. Study 2, however,
      revealed indirect positive relationships between primary outgroup contact and
      secondary outgroup attitudes via increased similarity complexity and overlap
      complexity. These relationships were obtained while controlling for two
      previously tested mediating mechanisms, attitude generalization (operationalized
      as primary outgroup attitude) and deprovincialization (operationalized as ingroup
      attitude and identification). We discuss the theoretical implications of these
      findings and the contribution of social identity complexity to understanding
      processes underlying STEs of contact. 

PMID- 23879328
TI  - Release and establishment of the parasitoid Diachasmimorpha kraussii against the
      tephritid fruit fly Bactrocera latifrons in Hawaii.
AB  - Diachasmimorpha kraussii (Fullaway) (Hymenoptera: Braconidae) was first released
      against Bactrocera latifrons (Hendel) (Diptera: Tephritidae) in Hawaii in March
      2003. Over a three month period, eight releases, totaling 7,696 females and 3,968
      males, were made in a turkeyberry, Solanum torvum Swartz (Solanales: Solanaceae)
      patch known to have a well established B. latifrons population. The establishment
      of D. kraussii was assessed through fruit collections conducted over a three-year
      period beyond the last release. D. kraussii was recovered 2 weeks, 31 months, and
      39 months after the last parasitoid release, with collections not only from the
      release site, but also from a control site about 5.0 km distance from the release
      site. Recovery from fruit collections three years after the last parasitoid
      release confirmed that D. kraussii had become established in Hawaii. Parasitism
      rates were low, only 1.0-1.4%, compared to rates of 2.8-8.7% for the earlier
      established egg-larval parasitoid, Fopius arisanus (Sonan).

PMID- 23879327
TI  - The role of hybridization in the origin and spread of asexuality in Daphnia.
AB  - The molecular mechanisms leading to asexuality remain little understood despite
      their substantial bearing on why sexual reproduction is dominant in nature. Here,
      we examine the role of hybridization in the origin and spread of obligate
      asexuality in Daphnia pulex, arguably the best-documented case of contagious
      asexuality. Obligately parthenogenetic (OP) clones of D. pulex have traditionally
      been separated into 'hybrid' (Ldh SF) and 'nonhybrid' (Ldh SS) forms because the
      lactase dehydrogenase (Ldh) locus distinguishes the cyclically parthenogenetic
      (CP) lake dwelling Daphnia pulicaria (Ldh FF) from its ephemeral pond dwelling
      sister species D. pulex (Ldh SS). The results of our population genetic analyses
      based on microsatellite loci suggest that both Ldh SS and SF OP individuals can
      originate from the crossing of CP female F1 (D. pulex * D. pulicaria) and
      backcross with males from OP lineages carrying genes that suppress meiosis
      specifically in female offspring. In previous studies, a suite of diagnostic
      markers was found to be associated with OP in Ldh SS D. pulex lineages. Our
      association mapping supports a similar genetic mechanism for the spread of
      obligate parthenogenesis in Ldh SF OP individuals. Interestingly, our study shows
      that CP D. pulicaria carry many of the diagnostic microsatellite alleles
      associated with obligate parthenogenesis. We argue that the assemblage of
      mutations that suppress meiosis and underlie obligate parthenogenesis in D. pulex
      originated due to a unique historical hybridization and introgression event
      between D. pulex and D. pulicaria. 

PMID- 23879329
TI  - Stereoselective pharmacodynamic and pharmacokinetic analysis of sec
      Butylpropylacetamide (SPD), a new CNS-active derivative of valproic acid with
      unique activity against status epilepticus.
AB  - sec-Butylpropylacetamide (racemic-SPD) is a chiral CNS-active amide derivative of
      valproic acid (VPA). This study describes synthesis and stereospecific
      comparative pharmacodynamics (PD, anticonvulsant activity and teratogenicity) and
      pharmacokinetic (PK) analysis of four individual SPD stereoisomers. SPD
      stereoisomers' anticonvulsant activity was comparatively evaluated in several
      anticonvulsant animal models including the benzodiazepine-resistant status
      epilepticus (SE). SPD stereoisomers' PK-PD relationship was evaluated in rats.
      Teratogenicity of SPD stereoisomers was evaluated in SWV mice strain, susceptible
      to VPA-induced neural tube defect (NTD). SPD stereoisomers (141 or 283 mg/kg) did
      not cause NTD. SPD has stereoselective PK and PD. (2R,3S)-SPD and (2S,3R)-SPD
      higher clearance led to a 50% lower plasma exposure that may contribute to their
      relative lower activity in the pilocarpine-induced SE model. (2S,3S)-SPD, (2R,3R)
      SPD, and racemic-SPD have similar anticonvulsant activity and a PK profile that
      are better than those of (2R,3S)-SPD and (2S,3R)-SPD, making them good candidates
      for development as new, potent antiepileptics with a potential in benzodiazepine
      resistant SE. 

PMID- 23879330
TI  - Structure confirmation of altertenuol.
AB  - Comparison of an authentic sample of altertenuol with altenuisol obtained by
      total synthesis and analysis of nuclear magnetic resonance spectra unambiguously
      revealed that altertenuol and altenuisol are identical compounds. 

PMID- 23879326
TI  - Hemodynamic regulation of reactive oxygen species: implications for vascular
      diseases.
AB  - SIGNIFICANCE: Arterial blood vessels functionally and structurally adapt to
      altering hemodynamic forces in order to accommodate changing needs and to provide
      stress homeostasis. This ability is achieved at the cellular level by converting
      mechanical stimulation into biochemical signals (i.e., mechanotransduction).
      Physiological mechanical stress helps maintain vascular structure and function,
      whereas pathologic or aberrant stress may impair cellular mechano-signaling, and
      initiate or augment cellular processes that drive disease. RECENT ADVANCES:
      Reactive oxygen species (ROS) may represent an intriguing class of mechanically
      regulated second messengers. Chronically enhanced ROS generation may be induced
      by adverse mechanical stresses, and is associated with a multitude of vascular
      diseases. Although a causal relationship has clearly been demonstrated in large
      numbers of animal studies, an effective ROS-modulating therapy still remains to
      be established by clinical studies. CRITICAL ISSUES AND FUTURE DIRECTIONS: This
      review article focuses on the role of various mechanical forces (in the form of
      laminar shear stress, oscillatory shear stress, or cyclic stretch) as modulators
      of ROS-driven signaling, and their subsequent effects on vascular biology and
      homeostasis, as well as on specific diseases such as arteriosclerosis,
      hypertension, and abdominal aortic aneurysms. Specifically, it highlights the
      significance of the various NADPH oxidase (NOX) isoforms as critical ROS
      generators in the vasculature. Directed targeting of defined components in the
      complex network of ROS (mechano-)signaling may represent a key for successful
      translation of experimental findings into clinical practice.

PMID- 23879331
TI  - MicroRNA profiling in the serums of SCA3/MJD patients.
AB  - Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is the most
      common type of spinocerebellar ataxia in China. However, the pathogenesis of
      SCA3/MJD is still unknown. MicroRNAs (miRNAs) have been repeatedly demonstrated
      to exist in human peripheral serum in a bio-stable form and have been shown to be
      useful biomarkers for other neurodegenerative disorders. However, no study of
      SCA3/MJD patients has assessed specific changes in regulatory miRNAs. Therefore,
      we systematically used the miRCURYTM LNA Array, followed by quantitative real
      time polymerase chain reaction validation, to access miRNA expression levels in
      the serums from SCA3/MJD patients. Our results show that miR-25, miR-125b, miR
      29a, and miR-34b could be potential biomarkers for SCA3/MJD and could be used to
      further investigate the pathogenesis of SCA3/MJD and drug development.

PMID- 23879332
TI  - Heterogeneous rate constants for indium mediated allylations: cinnamyl chloride
      in ethanol/water mixtures.
AB  - Indium mediated allylation (IMA) offers a powerful tool to synthetic chemists for
      creating carbon-carbon bonds. However, its rate limiting step, the heterogeneous
      reaction of allyl halides at solid indium surfaces, is still poorly understood.
      For example, solvent effects, especially the presence of water, on IMA are
      dramatic. We report for the first time rate constants for the heterogeneous rate
      limiting step of IMA. The rate constant for reaction of cinnamyl chloride on
      indium decreases from 5.5 * 10(-4) cm/s in 80% ethanol/20% water to 1 * 10(-4)
      cm/s in 99.8% ethanol/0.2% water. In addition, the percent water has a dramatic
      effect on induction time. This study further establishes photomicroscopy as a
      powerful tool for the determination of heterogeneous rate constants. 

PMID- 23879333
TI  - Water electrolysis and energy harvesting with zero-dimensional ion-sensitive
      field-effect transistors.
AB  - The relationship of the gas bubble size to the size distribution critically
      influences the effectiveness of electrochemical processes. Several optical and
      acoustical techniques have been used to characterize the size and emission
      frequency of bubbles. Here, we used zero-dimensional (0D) ion-sensitive field
      effect transistors (ISFETs) buried under a microbath to detect the emission of
      individual bubbles electrically and to generate statistics on the bubble emission
      time. The bubble size was evaluated via a simple model of the electrolytic
      current. We suggest that energy lost during water electrolysis could be used to
      generate electric pulses at an optimal efficiency with an array of 0D ISFETs. 

PMID- 23879334
TI  - Modelling in infectious diseases: between haphazard and hazard.
AB  - Modelling of infectious diseases is difficult, if not impossible. No epidemic has
      ever been truly predicted, rather than being merely noticed when it was already
      ongoing. Modelling the future course of an epidemic is similarly tenuous, as
      exemplified by ominous predictions during the last influenza pandemic leading to
      exaggerated national responses. The continuous evolution of microorganisms, the
      introduction of new pathogens into the human population and the interactions of a
      specific pathogen with the environment, vectors, intermediate hosts, reservoir
      animals and other microorganisms are far too complex to be predictable. Our
      environment is changing at an unprecedented rate, and human-related factors,
      which are essential components of any epidemic prediction model, are difficult to
      foresee in our increasingly dynamic societies. Any epidemiological model is, by
      definition, an abstraction of the real world, and fundamental assumptions and
      simplifications are therefore required. Indicator-based surveillance methods and,
      more recently, Internet biosurveillance systems can detect and monitor outbreaks
      of infections more rapidly and accurately than ever before. As the interactions
      between microorganisms, humans and the environment are too numerous and
      unexpected to be accurately represented in a mathematical model, we argue that
      prediction and model-based management of epidemics in their early phase are quite
      unlikely to become the norm. 

PMID- 23879335
TI  - Intranasal delivery of cyclobenzaprine hydrochloride-loaded thiolated chitosan
      nanoparticles for pain relief.
AB  - The purpose of present investigation was to formulate and characterize the
      cyclobenzaprine HCl (CBZ)-loaded thiolated chitosan nanoparticles and assessment
      of in-vitro cell viability, trans-mucosal permeability on RPMI2650 cell
      monolayer, in-vivo pharmacokinetic and pharmacodynamic study of thiolated
      chitosan nanoparticles on Swiss albino mice after intranasal administration. A
      significant high permeation of drug was observed from thiolated chitosan
      nanoparticles with less toxicity on nasal epithelial cells. Brain uptake of the
      drug after (99m)Tc labeling was significantly enhanced after thiolation of
      chitosan. CBZ-loaded thiolated chitosan NPs significantly reverse the N-Methyl-.
      Aspartate (NMDA)-induced hyperalgesia by intranasal administration than the CBZ
      solution. The studies of present investigation revealed that thiolation of
      chitosan significantly reduce trans-mucosal toxicity with enhanced trans-mucosal
      permeability via paracellular pathway and brain uptake of a hydrophilic drug
      (normally impermeable across blood brain barrier) and pain alleviation activity
      via intranasal route.

PMID- 23879336
TI  - Validation study of Doppler-derived transmitral valve gradients compared to near
      simultaneously obtained directly measured catheter gradients immediately after
      mitral valve repair surgery.
AB  - OBJECTIVE: To evaluate the accuracy of Doppler-derived transmitral valve
      gradients immediately after mitral valve repair by comparing them with near
      simultaneously obtained direct catheter gradients. DESIGN: A prospective study.
      SETTING: A tertiary care medical center. PARTICIPANTS: Twenty elective adult
      surgical patients presenting for mitral valve repair surgery. METHODS: Mitral
      valve surgery proceeded in standard fashion except for the use of a smaller than
      usual left ventricular vent catheter (Medtronic DLP 10 French left heart vent
      catheter). After completion of the mitral valve repair and subsequent cardiac de
      airing, the patient was weaned from cardiopulmonary bypass. Immediately after
      separation, the study period began. Near simultaneous transmitral Doppler
      gradients were obtained with directly measured catheter gradients via the vent
      catheter. RESULTS: While the mean peak gradient difference of 1.1 mmHg was small
      (p-value 0.18, 95% CI: -0.54 to 2.73 mmHg), the correlation between Doppler and
      catheter gradient measurements (Pearson correlation coefficient r = 0.54, p =
      0.055) only approached statistical significance due to the large variance
      associated with the small sample size. In all patients with a peak gradient
      greater than 10 mmHg (4 of the 20 patients), overestimation of catheter gradients
      by Doppler occurred, with two showing a 62% to 73% discrepancy. In these two
      cases, there was also evidence for elevated left ventricular end-diastolic
      pressure (LVEDP) along with high transmitral blood flow velocities. CONCLUSION:
      Doppler-derived transmitral gradients provide a simple, safe, and reliable
      measure of the true physiologic transmitral valve gradient. At the same time, it
      is important to recognize that significant Doppler over-estimation of catheter
      gradients may occur in patients with elevated Doppler transmitral velocities. The
      causes of these overestimations are unknown. They may be related to technical
      recording errors. They may also be related to an inherent weakness in Doppler
      technology--its inability to account for any distal recovery of pressure, which
      in a select group of patients could be significant.

PMID- 23879337
TI  - Commentary.

PMID- 23879338
TI  - Echocardiographic determinants of ischemic mitral regurgitation.
AB  - OBJECTIVES: It is not clear whether the presence and degree of chronic ischemic
      mitral regurgitation (IMR) in patients with left ventricular (LV) dysfunction are
      related to LV dysfunction, local LV remodeling or mitral valve deformation. We
      sought to establish the strongest determinants of IMR severity in patients with
      LV dysfunction and IMR. METHODS: We prospectively performed transthoracic
      echocardiography for 135 patients (mean age = 60.76 +/- 9.69 years, 71.9% male)
      with LV dysfunction (ejection fraction <= 50%) and coronary artery disease (70%
      stenosis in >= 1 coronary artery and no myocardial infarction during the previous
      16 days). Global and local LV remodeling and mitral deformity indices were
      measured. Using the vena contracta, MR severity was graded as no regurgitation;
      mild; moderate; and severe. RESULTS: Mild regurgitation was found in 45 (33.3%)
      patients, moderate in 71 (52.6%), severe in 6 (4.4%), and no regurgitation in 13
      (9.6%). By linear logistic multivariable analysis, the major echocardiographic
      determinants of MR severity were tenting area (TA), sphericity index (LV systolic
      length/width), and C-septal (distance between the leaflet coaptation and the
      septum). TA was best related to coaptation depth and annulus diameter. Mitral
      annular diameter was best correlated with left atrial surface area (r = 0.630, p
      < 0.001). CONCLUSION: TA was significantly correlated with annulus diameter and,
      along with sphericity index and C-septal, were the independent echocardiographic
      determinants of MR severity. These findings warrant consideration when performing
      mitral valve repairs for patients with IMR.

PMID- 23879339
TI  - Long-term effect of dual antiplatelet treatment after off-pump coronary artery
      bypass grafting.
AB  - OBJECTIVES: Recent studies have found increased long-term cardiovascular
      morbidity after off-pump coronary artery bypass surgery (OPCAB). We evaluated the
      efficacy and safety of dual antiplatelet therapy (DAT) in the prevention of
      cardiovascular events at two years after OPCAB surgery. METHODS: Retrospective
      study that included all patients that underwent OPCAB surgery in our institution
      between 2009 and 2010. Single or dual antiplatelet therapy was initiated at
      hospital discharge, and its effect in patients' prognosis was analyzed. Follow-up
      was conducted by telephone and using the hospital databases. The primary end
      point was the composite of acute coronary syndrome (ACS), revascularization,
      stroke, or cardiovascular death. RESULTS: The study included 237 patients divided
      into: (A) 128 patients who received single antiplatelet therapy and (B) 109
      patients who received dual antiplatelet therapy. The mean follow-up was 23.85
      months (standard deviation 0.5 months). 13.9% of patients had a primary end-point
      event. Patients in group A had a higher event rate compared with group B (18.8%
      vs. 8.3%, p = 0.02), with a significant reduction in hospital readmissions for
      ACS (10.9% vs. 3.7%, p = 0.035). In the multivariate analysis, dual antiplatelet
      therapy was an independent protective factor in the occurrence of events (hazard
      ratio = 0.395, 95% CI, 0.176 to 0.885, p = 0.024). There were no significant
      differences between the two groups with respect to bleeding events. CONCLUSION:
      Dual antiplatelet therapy after OPCAB surgery is associated with a decrease in
      the appearance of new cardiovascular events, due to a reduction in the number of
      hospital readmissions for ACS.

PMID- 23879340
TI  - Impact of electrocardiogram-gated multi-slice computed tomography-based aortic
      annular measurement in the evaluation of paravalvular leakage following
      transcatheter aortic valve replacement: the efficacy of the OverSized AortiC
      Annular ratio (OSACA ratio) in TAVR.
AB  - BACKGROUND: Even mild paravalvular leakage (PVL) after transcatheter aortic valve
      replacement (TAVR) is associated with increased late mortality. Electrocardiogram
      gated multi-slice computed tomography (MSCT) enables detailed aortic annulus
      assessment. We describe the impact of MSCT for PVL following TAVR. METHODS:
      Congruence between the prosthesis and annulus diameters affects PVL; therefore,
      we calculated the OverSized AortiC Annular ratio (OSACA ratio) and OSACA
      (transesophageal echocardiography, TEE) ratio as prosthesis diameter/annulus
      diameter on MSCT or TEE, respectively, and compared their relationship with PVL
      <= trace following TAVR. RESULTS: Of 36 consecutive patients undergoing TAVR
      (Group A), the occurrence of PVL <= trace (33.3%) was significantly related to
      the OSACA ratio (p = 0.00020). In receiver-operating characteristics analysis,
      the cutoff value of 1.03 for the OSACA ratio had the highest sum of sensitivity
      (75.0%) and specificity (91.7%; AUC = 0.87) with significantly higher
      discriminatory performance for PVL as compared to the OSACA (TEE) ratio (AUC =
      0.69, p = 0.028). In nine consecutive patients (Group B) undergoing TAVR based on
      guidelines formulated from our experience with Group A, PVL <= trace was
      significantly more frequent (88.9%) than that in Group A (p = 0.0060).
      CONCLUSIONS: The OSACA ratio has a significantly higher discriminatory
      performance for PVL <= trace than the OSACA (TEE) ratio, and aortic annular
      measurement from MSCT is more accurate than that from TEE.

PMID- 23879341
TI  - Bentall procedure for an adult patient with supravalvular aortic stenosis and
      coronary aneurysms.
AB  - We describe the surgical management of a 35-year-old male with multiple coronary
      aneurysms and a diffuse form of supravalvular aortic stenosis who presented with
      acute myocardial infarction and left ventricular dysfunction. The patient
      underwent a Bentall procedure with left internal mammary artery to left anterior
      descending artery bypass grafting with the use of cardiopulmonary bypass
      utilizing the right axillary artery for arterial cannulation.

PMID- 23879342
TI  - Alkaptonuria-associated aortic stenosis.
AB  - Alkaptonuria is an autosomal recessive disorder of tyrosine metabolism, which
      results in accumulation of unmetabolized homogentisic acid and its oxidized
      product in various tissues, including the heart. Cardiovascular involvement is a
      rare but serious complication of the disease. We present two patients who have
      undergone successful aortic valve replacement for alkaptonuria-associated aortic
      stenosis along with a review of the literature.

PMID- 23879343
TI  - Aortic cannula disruption following long-term LVAD support.
AB  - The Levitronix CentriMag is approved in Europe for 30 days as uni- or
      biventricular support in acute heart failure as a bridge to recovery, bridge to
      heart transplantation or to a long-term left ventricular assist device (LVAD). We
      report the case of a patient who was supported with the same Levitronix CentriMag
      pump for 119 days without changing any components of the circuit or the pump head
      because of an anatomical condition which precluded the feasibility of pump
      exchange and who did not experience any mechanical failure of the impeller but
      eventually died due to the rupture of the cannulae. This is the first report of
      failure of paracorporeal short-term LVAD due to disruption of one cannula with a
      properly functioning pump.

PMID- 23879344
TI  - Efficacy of straight versus angled interdental brushes on interproximal tooth
      cleaning: a randomized controlled trial.
AB  - BACKGROUND: To investigate interproximal biofilm reduction with an angled
      interdental brush as compared to a straight interdental brush (standard control)
      in a clinical, single-centre, single-blind, controlled, parallel-group trial.
      METHODS: Recruitment and examinations of the subjects were performed at the
      Witten/Herdecke University School of Dental Medicine. 128 volunteers, aged 20-65
      years, were recruited and stratified according to sex and age. Two groups with 64
      subjects each used either straight (standard control) or angled (test group)
      handgripped interdental toothbrushes of the same bristle stiffness. After a 12
      day home-care habituation period, participants received a professional tooth
      cleaning followed by a 48-h plaque regrowth period. At the intervention
      appointment, plaque was recorded with a fluorescent revelator and soft tissue
      damage was noted (T0 ). Interdental brushing was performed by the participant for
      2 min, and clinical parameters were recorded again (T1 ). The primary efficacy
      end point was the difference in modified Proximal Plaque Index (mPPI) after
      brushing compared to baseline. Secondary efficacy end points were mPPI
      differences in subgroups (anterior vs. posterior teeth; vestibular vs. oral tooth
      surfaces). Safety end point was the Danser gingival abrasion index (DI). RESULTS:
      mPPI showed lower scores after brushing within all (sub)groups (P < 0.01). mPPI
      brushing efficacy (DeltaT0  - T1 ) in subjects using straight interdental brushes
      was significantly higher as compared to angled interdental brushes (P < 0.0001).
      Straight interdental brushes were significantly more effective in posterior
      teeth, when used from vestibular and from oral tooth surfaces (P < 0.0001, P <
      0.01 and P < 0.0001, respectively). No significant differences were found between
      the groups in anterior teeth and concerning soft tissue damage. CONCLUSIONS:
      Straight interdental brushes may better remove plaque interproximally when
      compared to angled interdental brushes.

PMID- 23879345
TI  - An evaluation of meniscal collagenous structure using optical projection
      tomography.
AB  - BACKGROUND: The collagenous structure of menisci is a complex network of
      circumferentially oriented fascicles and interwoven radially oriented tie-fibres.
      To date, examination of this micro- architecture has been limited to two
      dimensional imaging techniques. The purpose of this study was to evaluate the
      ability of the three-dimensional imaging technique; optical projection tomography
      (OPT), to visualize the collagenous structure of the meniscus. If successful,
      this technique would be the first to visualize the macroscopic orientation of
      collagen fascicles in 3-D in the meniscus and could further refine load bearing
      mechanisms in the tissue. OPT is an imaging technique capable of imaging samples
      on the meso-scale (1-10 mm) at a micro-scale resolution. The technique, similar
      to computed tomography, takes two-dimensional images of objects from incremental
      angles around the object and reconstructs them using a back projection algorithm
      to determine three-dimensional structure. METHODS: Bovine meniscal samples were
      imaged from four locations (outer main body, femoral surface, tibial surface and
      inner main body) to determine the variation in collagen orientation throughout
      the tissue. Bovine stifles (n = 2) were obtained from a local abattoir and the
      menisci carefully dissected. Menisci were fixed in methanol and subsequently cut
      using a custom cutting jig (n = 4 samples per meniscus). Samples were then
      mounted in agarose, dehydrated in methanol and subsequently cleared using benzyl
      alcohol benzyl benzoate (BABB) and imaged using OPT. RESULTS: Results indicate
      circumferential, radial and oblique collagenous orientations at the contact
      surfaces and in the inner third of the main body of the meniscus. Imaging
      identified fascicles ranging from 80-420 MUm in diameter. Transition zones where
      fascicles were found to have a woven or braided appearance were also identified.
      The outer-third of the main body was composed of fascicles oriented predominantly
      in the circumferential direction. Blood vessels were also visualized using this
      technique, as their elastin content fluoresces more brightly than collagen at the
      425 nm wavelength used by the OPT scanner. CONCLUSIONS: OPT was capable of
      imaging the collagenous structure, as well as blood vessels in the bovine
      meniscus. Collagenous structure variability, including transition zones between
      structural regions not previously described in the meniscus, was identified using
      this novel technique.

PMID- 23879346
TI  - Methyl tert-butyl ether (MTBE) detected in abnormally high concentrations in
      postmortem blood and urine from two persons found dead inside a car containing a
      gasoline spill.
AB  - Two deep frozen persons, a female and a male, were found dead in a car. There had
      been an explosive fire inside the car which had extinguished itself. On the floor
      inside the car were large pools of liquid which smelled of gasoline. The autopsy
      findings and routine toxicological analyses could not explain the cause of death.
      Carboxyhemoglobin levels in the blood samples were <10%. Analysis with a
      headspace gas chromatography revealed methyl tert-butyl ether (MTBE)
      concentrations of 185 mg/L (female victim) and 115 mg/L (male victim) in
      peripheral blood. The urine MTBE concentrations were 150 mg/L and 256 mg/L,
      respectively. MTBE is a synthetic chemical which is added to gasoline as a fuel
      oxygenate. Gasoline poisoning is likely to be the cause of the death in these two
      cases, and MTBE can be a suitable marker of gasoline exposure, when other
      volatile components have vaporized. 

PMID- 23879347
TI  - Conjunctival melanomas and proton beam therapy.

PMID- 23879348
TI  - Proteomics analysis of oil body-associated proteins in the oleaginous diatom.
AB  - For biodiesel production from microalgae, it is desirable to understand the
      entire triacylglycerol (TAG) metabolism. TAG accumulation occurs in oil bodies,
      and although oil body-associated proteins could play important roles in TAG
      metabolism, only a few microalgal species have been studied by a comprehensive
      analysis. Diatoms are microalgae that are promising producers of biodiesel, on
      which such proteomics analysis has not been conducted to date. Herein, we
      identified oil body-associated proteins in the oleaginous diatom Fistulifera sp.
      strain JPCC DA0580. The oil body fraction was separated by cell disruption with
      beads beating and subsequent ultracentrifugation. Contaminating factors could be
      removed by comparing proteins from the oil body and the soluble fractions. This
      novel strategy successfully revealed 15 proteins as oil body-associated protein
      candidates. Among them, two proteins, which were parts of proteins predicted to
      have transmembrane domains, were indeed confirmed to specifically localize to the
      oil bodies in this strain by observation of GFP fusion proteins. One (predicted
      to be a potassium channel) was also detected from the ER, suggesting that oil
      bodies might originate from the ER. By utilizing this novel subtraction method,
      we succeeded in identifying the oil body-associated proteins in the diatom for
      the first time. 

PMID- 23879349
TI  - Polygonal vessels of rosacea are highlighted by dermoscopy.

PMID- 23879350
TI  - Metabolic syndrome in heart transplantation: impact on survival and renal
      function.
AB  - The aim of our study was to analyze the early presence of metabolic syndrome (MS)
      in heart transplant (HTx) patients, and to assess its long-term impact on
      survival and renal function. From January 2000 to October 2011, 253 consecutive
      HTx patients who survived more than 90 days were included. MS was diagnosed if
      patients met revised NCEP-ATP III criteria at HTx or within 3 months post-HTx.
      The prevalence of MS was 41.9%. Patients with MS had greater overall mortality
      after a mean follow-up of 1700 +/- 979 days (log-rank test, P = 0.020). In the
      multivariate analysis, and subject to a minimum survival of 90 days, the only
      independent predictor variables of long-term mortality were the presence of MS
      (OR, odds ratio 2.087, P = 0.032), and rejection episodes (OR 1.833, P = 0.001).
      Patients with MS had worse renal function at baseline both in plasma creatinine
      (1.19 +/- 0.44 vs. 1.03 +/- 0.29 mg/dl, P = 0.002) and glomerular filtration rate
      estimated by modified diet in renal disease (73.60 +/- 26.76 vs. 87.30 +/- 43.55
      ml/min/1.73 m(2) , P = 0.005), whereas progressive impairment of renal function
      was of equal magnitude in both groups. The presence of MS prior to transplant or
      its development within the first 3 months identified a subgroup at greater risk
      of mortality and long-term renal dysfunction.

PMID- 23879351
TI  - Male county jail inmates: a profile and self-reported human service needs by
      race.
AB  - With the enactment of the Second Chance Act in 2008, social workers have a
      greater opportunity for intervention to break the cycle of recidivism. To develop
      interventions, however, social workers require profiles of incarcerated people
      and their perceived human service needs. Unfortunately, previous research has
      focused on prison and not jail inmates and lacks race-differential data. In this
      article the authors address this gap in the literature by describing the scope of
      the problem and presenting a profile of male inmates and their perceived service
      needs by race upon entry into a major urban county jail. 

PMID- 23879352
TI  - Child maltreatment: the neurobiological aspects of posttraumatic stress disorder.
AB  - Childhood trauma due to physical abuse, neglect, or sexual abuse is a serious
      problem in the United States. Trauma can result in disruption or injury to the
      developing brain and lead to neurodevelopmental deficits that affect a child's
      functioning and can result in lifelong problems. Research has provided insight
      into how early childhood maltreatment affects brain development. This article
      examines the research on trauma, its effects on the brain, and evidence-based
      interventions. An overview of normal brain functioning and posttraumatic stress
      disorder is presented. Implications for social work practice with children who
      have experienced child maltreatment are discussed. 

PMID- 23879353
TI  - Comparative standards of evidence in social work.
AB  - In this article the authors analyze relevant and reliable evidence on the effects
      of the preferable treatment customized to each social work client. In doing so,
      the authors look at four major standards of evidence: (1) evidence-based
      practice, (2) collaboration models (i.e., the Cochrane Collaboration and the
      Campbell Collaboration), (3) knowledge translation, and (4) the Social Work
      Article Club. The ultimate goal of these standards of evidence is to successfully
      transfer research into practice. Currently, there is a gap between research and
      practice as a result of a lack of collaboration. Most social workers do not
      possess the skills to implement change in practice based on research evidence.
      The authors' objective is to increase understanding by instilling, in part,
      positive feelings toward research. 

PMID- 23879354
TI  - Evidence-based programs for schools: relationships between effect sizes and
      resource requirements.
AB  - Presumably, schools desiring larger effects from an empirically based program
      might be willing to allocate greater resources for the purchase and
      implementation of the intervention. However, while it may seem intuitive that
      more expensive programs generate greater change in student outcomes, there is
      currently a lack of evidence supporting such a relationship. In this study the
      authors address this gap in the literature by examining the critical relationship
      between resource requirements and effect sizes of 51 evidence-based programs that
      would influence school practitioners' choice of interventions. Through simple
      calculations of the range and mean resources for programs, analyses surprisingly
      found higher resource requirements for programs with the smallest effect sizes.
      Implications for practice and future research are discussed. 

PMID- 23879355
TI  - Factors associated with admission to a day school treatment program.
AB  - In this study the authors examine the individual and family characteristics of
      youth (N = 105) admitted over a five year period to a day school treatment
      program in a western New York community. All had exhausted alternative school
      placements within their home school districts and had a history of severe
      emotional or behavioral problems. Consistent with national patterns, more males
      (78%) than females were admitted, but in contrast to national trends, more
      Caucasians (63.8%) than students of color (36.2%) were admitted. Most lived in
      female headed single-parent households (51.4%). A few were foster children living
      with relatives or in non-relative foster homes (14.3%). Poverty was common with
      45.7% of these youth eligible for free lunches. Most were on psychotropic
      medications (57.1%) and had histories of outpatient (62.9%) and inpatient
      hospitalizations (23.6%) at admission. Involvement in the juvenile justice system
      was common with nearly a quarter involved in the juvenile justice system (n = 25;
      23.8%). 

PMID- 23879356
TI  - Establishing CASA as an evidence-based practice.
AB  - In this article the authors examine the evidentiary status of the Court Appointed
      Special Advocates (CASA) program through a review of current research findings
      and a critical analysis of the study methodologies used to produce those
      findings. Due to the equivocal research findings and widespread methodological
      weaknesses (most notably selection bias) in the literature base, it is determined
      that there is not currently enough evidence to establish CASA as an evidence
      based practice. In spite of the challenges to the feasibility of such research, a
      future research agenda is suggested that calls for the execution of large
      randomized controlled trials in order to produce findings that will inform a
      deeper understanding of CASA effectiveness in improving child outcomes. 

PMID- 23879357
TI  - Profiles and service utilization for children accessing a mental health walk-in
      clinic versus usual care.
AB  - Many children and adolescents with mental health problems do not receive the
      treatment they need. Unmet need raises questions about specific barriers that may
      prevent service use, and/or the characteristics of children and families who are
      less likely to receive care. Brief interventions or single-session psychotherapy
      delivered in a highly accessible manner are methods of addressing the problems
      associated with waitlists and limited access to care. In the current study the
      authors offer an exploratory evaluation of the West End Walk-In Counseling Centre
      for children and youth with psychosocial problems. Children 4 to 18 years of age
      who accessed the Walk-In Counseling Centre and a comparison group of clients who
      accessed usual care were assessed at intake, post-treatment, and 3-month follow
      up on demographic characteristics, behavioral/emotional adjustment and
      functioning, client satisfaction, and service use. Children in the walk-in group
      had more severe behavioral/emotional adjustment and functioning than usual care
      clients at baseline. At post-treatment, walk-in clients had lower scores on Total
      Mental Health Problems and Internalizing Behaviors, and exhibited fewer problems
      across all scales at follow-up. Walk-in clients found the wait time for service
      more reasonable and at follow-up, felt the service addressed concerns and had
      higher regard for counselor availability and cultural sensitivity of the service
      than usual care clients. Service utilization, assessed at post-treatment and 3
      month follow-up, showed that both groups were more likely to access mental health
      and education services rather than health or child welfare services, and were
      more likely to have used services in the 12 months prior to service than the 3
      months following service completion. Walk-in clients had steeper rates of
      improvement compared to usual care clients despite equivalence in psychosocial
      functioning at baseline. The walk-in model may be an effective alternative to
      usual care, particularly for those clients only willing to wait up to 2 weeks for
      service. 

PMID- 23879358
TI  - Operations research in HIV/AIDS.
AB  - Operations research is mainly applied to decision making in industries and
      corporations using quantitative methods to optimize production. The applications
      of operations research in social sciences research or health research in HIV,
      service delivery, and program performance improvement are minimal. Considering
      the complexity of the HIV/AIDS epidemic, it is imperative to learn from
      operations research in scaling up HIV treatment, prevention, and intervention in
      resource-poor settings. In this article the author discusses the methodological
      issues in operations research within the context of HIV/AIDS research. The author
      also suggests a framework for using operations research in the field of HIV/AIDS
      research and program intervention. 

PMID- 23879359
TI  - Avoiding type III, IV, and V errors through collaborative research.
AB  - Major types of empirical errors reviewed by a number of leading research
      textbooks include discussions of Type I and Type II errors. However, applied
      human service researchers can commit other types of errors that should be
      avoided. The potential benefits of the applied, collaborative research (in
      contrast to traditional participatory research) include an assurance that the
      study begins with the "right" questions that are important for community
      residents. Such research practice also helps generate useful research findings
      for decisions regarding redistribution of resources and resolving community
      issues. The aim of collaborative research is not merely to advance scientific
      understanding, but also to produce empirical findings that are usable for
      addressing priority needs and problems of distressed communities. A review of a
      case example (Garfield Community Assessment Study) illustrates the principles and
      practices of collaborative research. 

PMID- 23879360
TI  - Training needs assessment of service providers: targeted intervention for
      HIV/AIDS in Jharkhand, India.
AB  - Training needs assessments are pivotal for any capacity building program.
      Building capacity of service providers and staff involved in HIV/AIDS
      intervention programs is crucial because of the distinct nature of such programs.
      It requires specific knowledge, skills, and attitudes that are of utmost
      importance, influencing the reach of the program and its impact in halting and
      reversing the epidemic. This study was conducted to identify the training needs
      assessment of personnel involved in targeted intervention for high risk
      populations vulnerable to HIV infection in Jharkhand, India. Through the study
      the authors critically examine the existing training needs and gaps and suggest
      strategies to address them. 

PMID- 23879361
TI  - Symptoms of posttraumatic stress among child welfare workers who experience a
      maltreatment fatality on their caseload.
AB  - Annually, 1,000-2,000 child welfare workers experience the death of a child
      client. The child welfare field has paid increasing attention to the impact of
      workplace trauma events on the psychological distress of child welfare workers.
      In this article the author assesses the relationship between experiencing a
      maltreatment fatality and workers' posttraumatic stress among a multi-state
      sample of 385 child welfare workers. Results indicate that a maltreatment
      fatality is not associated with higher rates of posttraumatic stress. Among child
      welfare workers who experienced a fatality, those who feel greater culpability
      for the death report higher levels of posttraumatic stress. Implications for
      future research and practice are discussed. 

PMID- 23879362
TI  - Iron redox transformations in continuously photolyzed acidic solutions containing
      natural organic matter: kinetic and mechanistic insights.
AB  - In this work, the various pathways contributing to the formation and decay of
      Fe(II) in photolyzed acidic solutions containing Suwannee River fulvic acid
      (SRFA) are investigated. Results of experimental and computational studies
      suggest that ligand to metal charge transfer (LMCT), superoxide-mediated iron
      reduction and interaction with reduced organic species that are present
      intrinsically in SRFA each contribute to Fe(III) reduction with LMCT the most
      likely dominant pathway under these conditions. Fe(II) oxidation occurs as a
      result of its interaction with a variety of light-generated species including (i)
      short-lived organic species, (ii) relatively stable semiquinone-like organic
      species, and (iii) hydroperoxy radicals. While not definitive, a hypothesis that
      the short-lived organic species are similar to peroxyl radicals appears most
      consistent with our experimental and modeling results. The semiquinone-like
      organic species formed during photolysis by superoxide-mediated oxidation of
      reduced organic moieties are long-lived in the dark but prone to rapid oxidation
      by singlet oxygen ((1)O2) under irradiated conditions and thus play a minor role
      in Fe(II) oxidation in the light. A kinetic model is developed that adequately
      describes all aspects of the experimental data obtained and which is capable of
      predicting Fe(II) oxidation rates and Fe(III) reduction rates in the presence of
      natural organic matter and light. 

PMID- 23879363
TI  - Evaluation of colistin nephrotoxicity administered at different doses in the rat
      model.
AB  - OBJECTIVE: This study evaluated the usefulness of plasma Cystatin C (pCysC) along
      with urinary neutrophil gelatinase-associated lipocalin (NGAL), gamma
      glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase
      (ALP), aspartate (AST) and alanine (ALT) aminotransferase to monitor colistin
      nephrotoxicity. METHOD: Male rats were given intramuscular (i.m.) injections of
      colistin in doses of 150,000 (G1), 300,000 (G2) and 450,000 IU/kg/day (G3) or
      normal saline (Control), every 12 h for 7 days. After the 14th injection, animals
      were placed in metabolic cages and urine samples were collected in the next 12 h.
      Thereafter, animals were euthanized, blood samples were collected and kidneys
      were removed for histological assessment. RESULTS: Nephrotoxicity was completely
      dose-dependent according to pathologic findings. The major insults were acute
      tubular necrosis in the tubules of G3. No significant change in pCr was observed
      in all treated groups, but pCysC increased in the G3 compared to the control. In
      urinary markers, uNGAL level showed a dose dependant increase with significant
      change in the G2 and G3 groups compared to the control. However, there was no
      significant change in the AST, ALT, LDH or ALP activities but only GGT increased
      in the G3 compared to the control. CONCLUSION: Based on colistin doses used in
      our experimental study on rat model, histopathologic assessment remains the most
      accurate way to diagnose colistin nephrotoxicity. pCysC appears to be more
      reliable than pCr, and uNGAL seems to be the most sensitive factor of colistin
      nephrotoxicity.

PMID- 23879364
TI  - Association of decreased sympathetic nervous activity with mortality of older
      adults in long-term care.
AB  - AIM: To investigate the relationship between physical function, mortality and
      autonomic nervous activity measured by heart rate variability of elderly in long
      term care. METHODS: Cross-sectional and longitudinal studies were carried out at
      hospitals and health service facilities for the elderly in Nagano prefecture,
      Japan, from July 2007 to March 2011. A total of 105 long-term care older adults
      and 17 control older adults with independent physical function were included. The
      Functional Independence Measure (FIM) and Barthel Index were determined as
      indices of physical function. Twenty-four-hour Holter monitoring was carried out.
      From RR intervals in electrocardiograms, heart rate and standard deviations of
      all NN intervals in all 5-min segments of the entire recording, power spectral
      density, low frequency, high frequency and low frequency/high frequency (LF/HF)
      were calculated. RESULTS: FIM score and Barthel Index were 46 +/- 26 and 30 +/-
      31, respectively, in long-term care elderly. FIM and Barthel index were
      significantly correlated with heart rate and the standard deviations of all NN
      intervals after adjustment for age, sex, cardiovascular risk factors and FIM.
      Furthermore, LF/HF was significantly decreased in long-term care elderly compared
      with control elderly after adjustment for covariates. In addition, decrease in
      LF/HF was an independent risk factor for mortality. CONCLUSION: Low LF/HF
      activity was observed in long-term care elderly and was related to an increase of
      overall mortality.

PMID- 23879365
TI  - Developmental trajectory of intestinal MDR1/ABCB1 mRNA expression in children.

PMID- 23879366
TI  - Naphthodithiophenediimide (NDTI): synthesis, structure, and applications.
AB  - A straightforward synthesis of alpha,beta-unsubstituted and alpha-halogenated
      naphtho[2,3-b:6,7-b']dithiophenediimides (NDTIs) is described. Electrochemical
      and optical studies of N,N-dioctyl-NDTI demonstrate that the compound has a low
      lying LUMO energy level (4.0 eV below the vacuum level) and a small HOMO-LUMO gap
      (~2.1 eV). With its interesting electronic and optical properties, in addition to
      its planar structure, NDTI is a promising building block for the development of
      novel pi-functional materials. In fact, it afforded n-channel, p-channel, and
      ambipolar materials, depending on the molecular modification.

PMID- 23879368
TI  - Nanoscale structure and microscale stiffness of DNA nanotubes.
AB  - We measure the stiffness of tiled DNA nanotubes (HX-tubes) as a function of their
      (defined) circumference by analyzing their micrometer-scale thermal deformations
      using fluorescence microscopy. We derive a model that relates nanoscale features
      of HX-tube architecture to the measured persistence lengths. Given the known
      stiffness of double-stranded DNA, we use this model to constrain the average
      spacing between and effective stiffness of individual DNA duplexes in the tube. A
      key structural feature of tiled nanotubes that can affect stiffness is their
      potential to form with discrete amounts of twist of the DNA duplexes about the
      tube axis (supertwist). We visualize the supertwist of HX-tubes using electron
      microscopy of gold nanoparticles, attached to specific sites along the nanotube.
      This method reveals that HX-tubes tend not to form with supertwist unless forced
      by sequence design, and, even when forced, supertwist is reduced by elastic
      deformations of the underlying DNA lattice. We compare the hybridization energy
      gained upon closing a duplex sheet into a tube with the elastic energy paid for
      deforming the sheet to allow closure. In estimating the elastic energy we account
      for bending and twisting of the individual duplexes as well as shearing between
      them. We find the minimum supertwist state has minimum free energy, and global
      untwisting of forced supertwist is energetically favorable, consistent with our
      experimental data. Finally, we show that attachment of Cy3 dyes or changing
      counterions can cause nanotubes to adopt a permanent writhe with micrometer-scale
      pitch and amplitude. We propose that the coupling of local twist and global
      counter-twist may be useful in characterizing perturbations of DNA structure. 

PMID- 23879370
TI  - Functional responses and prey-stage preferences of a predatory gall midge and two
      predacious mites with twospotted spider mites, Tetranychus urticae, as host.
AB  - The twospotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is
      an important pest of vegetables and other economically important crops. This
      study evaluated the functional responses and prey-stage preferences of three
      species of predators, a predatory gall midge, Feltiella acarisuga (Vallot)
      (Diptera: Cecidomyiidae), and two predatory mite species, Neoseiulus californicus
      (McGregor) (Acari: Phytoseiidae) and Amblyseius swirskii (AnthiasHenriot), with
      T. urticae as the host, under laboratory conditions. The results showed that F.
      acarisuga was highly effective and the two species of predacious mites were
      moderately effective in feeding on T. urticae eggs. Logistic regression analysis
      suggested Type II (convex) functional responses for all three species. However,
      based on the estimates of the handling time and the attacking rates, the three
      predators had different predation capacities. Among the three species, F.
      acarisuga had the highest predation on T. urticae. The maximum daily predation by
      a larval F. acarisuga was 50 eggs/day, followed by a female N. californicus (25.6
      eggs/day) and a female A. swirskii (15.1 eggs/day). A female N. californicus
      produced more eggs than a female A. swirskii did when they both fed on T. urticae
      eggs. In addition, all three predator species had no preystage preference for
      either prey eggs or nymphs. The findings from this study could help select better
      biological control agents for effective control of T. urticae and other pests in
      vegetable productions.

PMID- 23879371
TI  - Exogenously added BMP-6, BMP-7 and VEGF may not enhance the osteogenic
      differentiation of human adipose stem cells.
AB  - In the present study bone morphogenetic protein (BMP)-6 alone or in synergy with
      BMP-7 and vascular endothelial growth factor (VEGF) were tested with human
      adipose stem cells (hASCs) seeded on cell culture plastic or 3D bioactive glass.
      Osteogenic medium (OM) was used as a positive control for osteogenic
      differentiation. The same growth factor groups were also tested combined with OM.
      None of the growth factor treatments could enhance the osteogenic differentiation
      of hASCs in 3D- or 2D-culture compared to control or OM. In 3D-culture OM
      promoted significantly total collagen production, whereas in 2D-culture OM
      induced high total ALP activity and mineralization compared to control and growth
      factors groups, but also high cell proliferation. In this study, hASCs did not
      respond to exogenously added growth although various parameters of the study set
      up may have affected these findings contradictory to the previous literature.

PMID- 23879367
TI  - Noncoding RNAs in DNA repair and genome integrity.
AB  - SIGNIFICANCE: The well-studied sequences in the human genome are those of protein
      coding genes, which account for only 1%-2% of the total genome. However, with the
      advent of high-throughput transcriptome sequencing technology, we now know that
      about 90% of our genome is extensively transcribed and that the vast majority of
      them are transcribed into noncoding RNAs (ncRNAs). It is of great interest and
      importance to decipher the functions of these ncRNAs in humans. RECENT ADVANCES:
      In the last decade, it has become apparent that ncRNAs play a crucial role in
      regulating gene expression in normal development, in stress responses to internal
      and environmental stimuli, and in human diseases. CRITICAL ISSUES: In addition to
      those constitutively expressed structural RNA, such as ribosomal and transfer
      RNAs, regulatory ncRNAs can be classified as microRNAs (miRNAs), Piwi-interacting
      RNAs (piRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs),
      and long noncoding RNAs (lncRNAs). However, little is known about the biological
      features and functional roles of these ncRNAs in DNA repair and genome
      instability, although a number of miRNAs and lncRNAs are regulated in the DNA
      damage response. FUTURE DIRECTIONS: A major goal of modern biology is to identify
      and characterize the full profile of ncRNAs with regard to normal physiological
      functions and roles in human disorders. Clinically relevant ncRNAs will also be
      evaluated and targeted in therapeutic applications.

PMID- 23879374
TI  - Regulation and direction of umbilical cord blood mesenchymal stem cells to adopt
      neuronal fate.
AB  - Umbilical cord blood mesenchymal stem cells (UCB-MSCs) transplantation is
      becoming a promising and attractive cell-based treatment modality for repairing
      the damaged central nervous system due to its advantages of low immunogenicity,
      wide range of sources, and less ethical controversy. One of the limitations of
      this approach is that the proportion of neurons differentiated from UCB-MSCs
      still remains at low level. Thus, to induce UCB-MSCs to differentiate into neuron
      like cells with a higher proportion is one of the key technologies of
      regenerative medicine and tissue engineering. Many induction protocols with
      remarkably higher differentiation rate to neurons have been reported. However,
      each protocol has its pros and cons and whether the neurons differentiated from
      UCB-MSCs under a certain protocol has normal nerve function remains
      controversial. Therefore, to guarantee the success of future clinical
      applications of UCB-MSCs, more investigations should be performed to improve the
      induction method and differentiation efficiency. 

PMID- 23879372
TI  - Idiopathic dilated cardiomyopathy and chronic atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is common in idiopathic dilated
      cardiomyopathy (IDC). We explored the clinical characteristics of IDC patients
      with chronic AF compared with those with sinus rhythm (SR). METHODS: A group of
      patients with IDC underwent extensive non-invasive and invasive evaluation during
      a hospitalization period. The patients were further divided into two groups with
      AF (n = 19) and SR (n = 68). RESULTS: Left atrial diameter was greater (P<0.001),
      left ventricular end-diastolic diameter smaller (P<0.05), left ventricular end
      diastolic and end-systolic volumes smaller (P<0.01 for all), mean pulmonary
      artery pressure and pulmonary capillary wedge pressure higher (P<0.05 for both),
      cardiac output and maximal oxygen consumption lower (P<0.01 and P<0.05,
      respectively), and the levels of N-terminal pro-brain natriuretic peptide and
      interleukin-6 higher (P<0.05 for both) in AF group compared with SR group. Left
      ventricular ejection fraction and left ventricular end-diastolic pressure were
      similar in both groups. CONCLUSIONS: In spite of otherwise more unfavourable
      prognostic factor profile, left ventricular size was observed to be smaller in
      chronic AF compared with SR in well-characterized patients with IDC. The
      confirmation and possible explainers of this paradoxical phenomenon need further
      studies in larger patient cohorts.

PMID- 23879373
TI  - Selective serotonin 2A receptor antagonism attenuates the effects of amphetamine
      on arousal and dopamine overflow in non-human primates.
AB  - The objective of the present study was to further elucidate the mechanisms
      involved in the wake-promoting effects of psychomotor stimulants. Many previous
      studies have tightly linked the effects of stimulants to dopamine
      neurotransmission, and some studies indicate that serotonin 2A receptors modulate
      these effects. However, the role of dopamine in arousal is controversial, most
      notably because dopamine neurons do not change firing rates across arousal
      states. In the present study, we examined the wake-promoting effects of the
      dopamine-releaser amphetamine using non-invasive telemetric monitoring. These
      effects were evaluated in rhesus monkeys as a laboratory animal model with high
      translational relevance for human disorders of sleep and arousal. To evaluate the
      role of dopamine in the wake-promoting effects of amphetamine, we used in vivo
      microdialysis targeting the caudate nucleus, as this approach provides clearly
      interpretable measures of presynaptic dopamine release. This is beneficial in the
      present context because some of the inconsistencies between previous studies
      examining the role of dopamine in arousal may be related to differences between
      postsynaptic dopamine receptors. We found that amphetamine significantly and dose
      dependently increased arousal at doses that engendered higher extracellular
      dopamine levels. Moreover, antagonism of serotonin 2A receptors attenuated the
      effects of amphetamine on both wakefulness and dopamine overflow. These findings
      further elucidate the role of dopamine and serotonin 2A receptors in arousal, and
      they suggest that increased dopamine neurotransmission may be necessary for the
      wake-promoting effects of amphetamine, and possibly other stimulants.

PMID- 23879375
TI  - A crossed beam and ab initio investigation on the formation of boronyldiacetylene
      (HCCCC11BO; X1Sigma+) via the reaction of the boron monoxide radical (11BO;
      X2Sigma+) with diacetylene (C4H2; X1Sigmag(+)).
AB  - The reaction dynamics of the boron monoxide radical ((11)BO; X(2)Sigma(+)) with
      diacetylene (C4H2; X(1)Sigmag(+)) were investigated at a nominal collision energy
      of 17.5 kJ mol(-1) employing the crossed molecular beam technique and supported
      by ab initio and statistical (RRKM) calculations. The reaction is governed by
      indirect (complex forming) scattering dynamics with the boron monoxide radical
      adding with its boron atom to the carbon-carbon triple bond of the diacetylene
      molecule at one of the terminal carbon atoms without entrance barrier. This leads
      to a doublet radical intermediate (C4H2(11)BO), which undergoes unimolecular
      decomposition through hydrogen atom emission from the C1 carbon atom via a tight
      exit transition state located about 18 kJ mol(-1) above the separated products.
      This process forms the hitherto elusive boronyldiacetylene molecule (HCCCC(11)BO;
      X(1)Sigma(+)) in a bimolecular gas phase reaction under single collision
      conditions. The overall reaction was determined to be exoergic by 62 kJ mol(-1).
      The reaction dynamics are compared to the isoelectronic diacetylene (C4H2;
      X(1)Sigmag(+))-cyano radical (CN; X(2)Sigma(+)) system studied previously in our
      group. The characteristics of boronyl-diacetylene and the boronyldiacetylene
      molecule (HCCCC(11)BO; X(1)Sigma(+)) as well as numerous intermediates are
      reported for the first time. 

PMID- 23879376
TI  - KHA-CARI Guideline: use of iron in chronic kidney disease patients.

PMID- 23879377
TI  - Interfaced metal heterodimers in the quantum size regime.
AB  - Synthesis of nanoparticle dimers made of asymmetric compositions is very
      challenging because of the difficulty in manipulating the nanoparticles' surface
      chemistries in order to control the assembly and/or growth of different
      nanoparticles. In this Letter, we report a seed-mediated, surface-confined
      epitaxial overgrowth strategy that enables the synthesis of high-quality
      interfaced Au-Ag heterodimers in the quantum size regime (diameters <10 nm). Au
      and Ag share a common face-centered cubic lattice and have nearly identical
      lattice constants, which facilitates epitaxial overgrowth and allows direct
      contact between the Au and Ag domains. Quantum size effects, formation of the
      Au/Ag interfaces, and chemical interactions with surfactant molecules strongly
      influence the optical properties of the dimers and lead to the observation of
      unique surface plasmon resonances. In particular, we find an unusual enhancement
      of the characteristic Au surface plasmon resonance and the emergence of a charge
      transfer plasmon across the Au/Ag domains, which together lead to broad-band
      absorption spanning visible to near-infrared wavelengths. A model that captures
      the changes in optical behavior due to chemical interactions and quantum size
      effects is used to calculate the absorption spectra of the interfaced
      heterodimers, resulting in good agreement with experimental measurements. 

PMID- 23879378
TI  - Effect of Methadone Dose on Maintenance Treatment and Health Consequences Among
      Heroin Addicts in South China.
AB  - A retrospective cross-sectional study was conducted with a convenience sample of
      197 adults receiving methadone maintenance treatment in Kunming city, South
      China, in 2010. The aim of the study was to determine the association of
      methadone maintenance dose on a variety of treatment outcomes. Treatment
      modalities, the adverse reactions to methadone treatment, the physical and mental
      outcomes of the treatment, and risk behavior changes were assessed. Multilevel
      negative and logistic binomial regression analyses were carried out, which
      demonstrated that methadone maintenance dose in this sample was not associated
      with improved treatment adherence or with quality of life. We concluded that dose
      had a small, if negligible, influence on the changes in adverse effects of
      methadone. Further research in dose differences between the genders should be
      conducted.

PMID- 23879381
TI  - Structure-guided design of novel thiazolidine inhibitors of O-acetyl serine
      sulfhydrylase from Mycobacterium tuberculosis.
AB  - The cysteine biosynthetic pathway is absent in humans but essential in microbial
      pathogens, suggesting that it provides potential targets for the development of
      novel antibacterial compounds. CysK1 is a pyridoxalphosphate-dependent O-acetyl
      sulfhydrylase, which catalyzes the formation of l-cysteine from O-acetyl serine
      and hydrogen sulfide. Here we report nanomolar thiazolidine inhibitors of
      Mycobacterium tuberculosis CysK1 developed by rational inhibitor design. The
      thiazolidine compounds were discovered using the crystal structure of a CysK1
      peptide inhibitor complex as template. Pharmacophore modeling and subsequent in
      vitro screening resulted in an initial hit compound 2 (IC50 of 103.8 nM), which
      was subsequently optimized by a combination of protein crystallography, modeling,
      and synthetic chemistry. Hit expansion of 2 by chemical synthesis led to improved
      thiazolidine inhibitors with an IC50 value of 19 nM for the best compound, a 150
      fold higher potency than the natural peptide inhibitor (IC50 2.9 MUM).

PMID- 23879380
TI  - DNA methylation of the glucagon-like peptide 1 receptor (GLP1R) in human
      pancreatic islets.
AB  - BACKGROUND: Insulin secretion is enhanced upon the binding of Glucagon-like
      peptide-1 (GLP-1) to its receptor (GLP1R) in pancreatic beta cells. Although a
      reduced expression of GLP1R in pancreatic islets from type 2 diabetic patients
      and hyperglycaemic rats has been established, it is still unknown if this is
      caused by differential DNA methylation of GLP1R in pancreatic islets of type 2
      diabetic patients. METHODS: In this study, DNA methylation levels of 12 CpG sites
      close to the transcription start site of GLP1R were analysed in pancreatic islets
      from 55 non-diabetic and 10 type 2 diabetic human donors as well as in beta and
      alpha cells isolated from human pancreatic islets. DNA methylation of GLP1R was
      related to GLP1R expression, HbA1c levels and BMI. Moreover, mRNA expression of
      MECP2, DNMT1, DNMT3A and DNMT3B was analysed in pancreatic islets of the non
      diabetic and type 2 diabetic donors. RESULTS: One CpG unit, at position +199 and
      +205 bp from the transcription start site, showed a small increase in DNA
      methylation in islets from donors with type 2 diabetes compared to non-diabetic
      donors (0.53%, p=0.02). Furthermore, DNA methylation levels of one CpG site
      located 376 bp upstream of the transcription start site of GLP1R correlated
      negatively with GLP1R expression (rho=-0.34, p=0.008) but positively with BMI and
      HbA1c (rho=0.30, p=0.02 and rho=0.30, p=0.03, respectively). This specific CpG
      site is located in an area with known SP1 and SP3 transcription factor binding
      sites. Moreover, when we compared the DNA methylation of the GLP1R promoter in
      isolated human beta and alpha cells, we found that it was higher in alpha-
      compared with beta-cells (p=0.009). Finally, there was a trend towards decreased
      DNMT3A expression (p=0.056) in type 2 diabetic compared with non-diabetic islets.
      CONCLUSIONS: Together, our study shows that while BMI and HbA1c are positively
      associated with DNA methylation levels of GLP1R, its expression is negatively
      associated with DNA methylation of GLP1R in human pancreatic islets.

PMID- 23879382
TI  - The impact of right ventricular stroke work on B-type natriuretic peptide levels
      in patients with mitral stenosis undergoing percutaneous mitral valvuloplasty.
AB  - OBJECTIVES: We aimed to explore the relationship between brain natriuretic
      peptide (BNP) levels and right ventricular (RV) function in patients with mitral
      stenosis (MS), and to investigate the hemodynamic parameters that predict
      reduction of BNP levels after percutaneous mitral valvuloplasty (PMV).
      BACKGROUND: Few studies have evaluated BNP in the context of MS, specifically the
      impact of the RV stroke work (RVSW) on serum BNP levels has not been defined.
      METHODS: Thirty patients with symptomatic rheumatic MS in sinus rhythm who were
      referred for a PMV were enrolled. Right and left heart pressures were obtained
      before and after valvuloplasty. RVSW index (RVSWI) was calculated by cardiac
      catheterization. RESULTS: Basal BNP levels were elevated in MS patients and
      correlated with several hemodynamic parameters including pulmonary pressure,
      pulmonary vascular resistance index, cardiac index (CI), and RVSWI. In
      multivariate analysis, CI and RVSWI were independent predictors of raised basal
      BNP levels. PMV resulted in a significant decrease in the RVSWI with a concurrent
      increase in CI (2.4 +/- 0.43 to 2.9 +/- 0.8 L/min/m(2), P = 0.010). Overall,
      plasma BNP levels significantly decreased from 124 (63/234) to 73 (48/148) pg/ml
      postvalvuloplasty. Multivariate analysis revealed that the reduction of left
      atrial (LA) pressure post-PMV was an independent predictor of change in BNP
      levels. CONCLUSIONS: Elevated baseline BNP level in MS patients was independently
      associated with CI and RVSWI. Plasma BNP levels were reduced after successful
      PMV, which was associated with the reduction of the LA pressure.

PMID- 23879383
TI  - Effects of ulipristal acetate on sperm DNA fragmentation during in vitro
      incubation.
AB  - OBJECTIVE: Ulipristal acetate (UPA) acts as an emergency contraceptive by
      inhibiting ovulation. This study explores possible additional effects on the
      fragmentation of sperm DNA during in vitro incubation. METHODS: Motile
      spermatozoa from healthy donors were selected by swim-up and incubated under
      capacitating conditions in control medium or with UPA (1, 10, 100, 1,000 or
      10,000 ng/ml). In some experiments, 200 MUM of H2O2 were added to induce
      oxidative stress. The sperm chromatin dispersion test was performed to analyse
      DNA integrity (400 cells; 1000*). Lipid peroxidation (thiobarbituric acid assay),
      induced-acrosome reaction (AR) and sperm vitality (Eosin Y) were also evaluated
      in spermatozoa exposed to UPA and/or H2O2. RESULTS: During sperm incubation, the
      percentage of fragmented DNA increased significantly, from 15.0 +/- 1.3 to 41.0
      +/- 4.5% (p < 0.001). In the presence of UPA, DNA fragmentation decreased
      significantly (p < 0.05), in a dose-dependent manner. At 100 and 1000 ng/ml, UPA
      also counteracted the effect of H2O2 and prevented DNA fragmentation. No effect
      on sperm vitality, lipid peroxidation or induced-AR was found with any treatment.
      CONCLUSIONS: During in vitro sperm capacitation DNA fragmentation increased but
      the latter was counteracted in the presence of UPA, which possibly acted as a
      scavenger of reactive oxygen species produced by spermatozoa.

PMID- 23879384
TI  - Near-infrared lymphography as a minimally invasive modality for imaging lymphatic
      reconstitution in a rat orthotopic hind limb transplantation model.
AB  - Wider application of vascularized composite allotransplantation (VCA) is limited
      by the need for chronic immunosuppression. Recent data suggest that the lymphatic
      system plays an important role in mediating rejection. This study used near
      infrared (NIR) lymphography to describe lymphatic reconstitution in a rat VCA
      model. Syngeneic (Lewis-Lewis) and allogeneic (Brown Norway-Lewis) rat orthotopic
      hind limb transplants were performed without immunosuppression. Animals were
      imaged pre- and postoperatively using indocyanine green (ICG) lymphography.
      Images were collected using an NIR imaging system. Co-localization was achieved
      through use of an acrylic paint/hydrogen peroxide mixture. In all transplants,
      ICG first crossed graft suture lines on postoperative day (POD) 5. Clinical signs
      of rejection also appeared on POD 5 in allogeneic transplants, with most
      exhibiting Grade 3 rejection by POD 6. Injection of an acrylic paint/hydrogen
      peroxide mixture on POD 5 confirmed the existence of continuous lymphatic vessels
      crossing the suture line and draining into the inguinal lymph node. NIR
      lymphography is a minimally invasive imaging modality that can be used to study
      lymphatic vessels in a rat VCA model. In allogeneic transplants, lymphatic
      reconstitution correlated with clinical rejection. Lymphatic reconstitution may
      represent an early target for immunomodulation. 

PMID- 23879385
TI  - Prevalence of prescription and illicit drugs in pregnancy-associated non-natural
      deaths of Florida mothers, 1999-2005.
AB  - Abuse of prescription and illicit drugs has been rapidly increasing. This study
      examines the prevalence of drug use in the non-natural deaths of pregnant or
      recently pregnant women. Records from Florida's Pregnancy Associated Mortality
      Review conducted between 1999 and 2005 (n = 415) were linked to 385 toxicology
      reports obtained from Florida medical examiners' offices. The final study sample
      consisted of 169 drug-positive, pregnancy-associated non-natural deaths. Of
      these, 86 were positive for both blood and urine, 64 were positive for blood only
      and five for urine only, and the remainder were positive for some other specimen.
      Among these deaths, 91 cases (54%) involved prescription drugs, 78 cases (46%)
      involved illicit drugs, and 69 cases (41%) involved alcohol. Opioids constituted
      the majority of deaths associated with prescription drugs. Substantial co-use of
      opioids and benzodiazepines was seen. Pregnant or recently pregnant women may
      have more interactions with healthcare providers, which may present more
      opportunities for intervention and prevention.

PMID- 23879386
TI  - Semi-automated retinal vessel analysis in nonmydriatic fundus photography.
AB  - PURPOSE: Funduscopic assessment of the retinal vessels may be used to assess the
      health status of microcirculation and as a component in the evaluation of
      cardiovascular risk factors. Typically, the evaluation is restricted to
      morphological appreciation without strict quantification. Our purpose was to
      develop and validate a software tool for semi-automated quantitative analysis of
      retinal vasculature in nonmydriatic fundus photography. METHODS: matlab software
      was used to develop a semi-automated image recognition and analysis tool for the
      determination of the arterial-venous (A/V) ratio in the central vessel equivalent
      on 45 degrees  digital fundus photographs. Validity and reproducibility of the
      results were ascertained using nonmydriatic photographs of 50 eyes from 25
      subjects recorded from a 3DOCT device (Topcon Corp.). Two hundred and thirty
      three eyes of 121 healthy subjects were evaluated to define normative values.
      RESULTS: A software tool was developed using image thresholds for vessel
      recognition and vessel width calculation in a semi-automated three-step
      procedure: vessel recognition on the photograph and artery/vein designation,
      width measurement and calculation of central retinal vessel equivalents. Mean
      vessel recognition rate was 78%, vessel class designation rate 75% and
      reproducibility between 0.78 and 0.91. Mean A/V ratio was 0.84. Application on a
      healthy norm cohort showed high congruence with prior published manual methods.
      Processing time per image was one minute. CONCLUSIONS: Quantitative geometrical
      assessment of the retinal vasculature may be performed in a semi-automated manner
      using dedicated software tools. Yielding reproducible numerical data within a
      short time leap, this may contribute additional value to mere morphological
      estimates in the clinical evaluation of fundus photographs.

PMID- 23879387
TI  - A review of interprofessional dissemination and education interventions for
      recognizing and managing dementia.
AB  - The number of individuals with dementia is expected to increase dramatically over
      the next 20 years. Given the complicated clinical, sociobehavioral, and
      caregiving skills that are needed to comprehensively assess and manage
      individuals with dementia, the gold standard of care requires involvement of
      interprofessional teams. This systematic review examined 4,023 abstracts, finding
      18 articles from 16 studies where an interprofessional dissemination program was
      performed. Most studies found some improvement in clinician knowledge or
      confidence, or patient outcomes, though methods and patient and clinician
      populations were disparate. Although a significant evidence base for assessing
      and managing individuals with dementia has been developed, few studies have
      examined how to disseminate this research, and even fewer in an interprofessional
      manner. These findings suggest that greater emphasis needs to be placed on
      disseminating existing evidence-based care and ensuring that programs are
      interprofessional in nature so that excellent, patient-centered care is provided.

PMID- 23879388
TI  - A neonatal case of proliferative nodules in a giant congenital melanocytic nevus
      with histological evaluation.

PMID- 23879389
TI  - Comparative proteomic analysis of generative and sperm cells reveals molecular
      characteristics associated with sperm development and function specialization.
AB  - In flowering plants, two sperm cells (SCs) are generated from a generative cell
      (GC) in the developing pollen grain or growing pollen tube and are then delivered
      to the embryo sac to initiate double fertilization. SC development and function
      specialization involve the strict control of the protein (gene) expression
      program and coordination of diverse cellular processes. However, because methods
      for collecting a large amount of highly purified GCs and SCs for proteomic and
      transcriptomic studies from a plant are not available, molecular information
      about the program and the interconnections is lacking. Here, we describe a method
      for obtaining a large quantity of highly purified GCs and SCs from just
      germinated lily pollen grains and growing pollen tubes for proteomic analysis.
      Our observation showed that SCs had less condensed chromatin and more vacuole
      like structures than GCs and that mature SCs were arrested at the G2 phase.
      Comparison of SC and GC proteomes revealed 101 proteins differentially expressed
      in the two proteomes. These proteins are involved in diverse cellular and
      metabolic processes, with preferential involvement in metabolism, the cell cycle,
      signaling, the ubiquitin/proteasome pathway, and chromatin remodeling.
      Impressively, almost all proteins in SCF complex-mediated proteolysis and the
      cell cycle were up-regulated in SCs, whereas those in chromatin remodeling and
      stress response were down-regulated. Our data also reveal the coordination of SCF
      complex-mediated proteolysis, cell cycle progression, and DNA repair in SC
      development and function specialization. This study revealed for the first time a
      difference in protein profiles between GCs and SCs. 

PMID- 23879390
TI  - Time-resolved energy-momentum spectroscopy of electric and magnetic dipole
      transitions in Cr3+:MgO.
AB  - Due to the recent interest in magnetic light-matter interactions, the magnetic
      dipole (MD) transitions in lanthanide ions have been studied for potential
      applications in nano-optics. Similar to lanthanide ions, transition-metal ions
      also exhibit strong MD emission at room temperature, but their prominent MD zero
      phonon lines are often accompanied by significant electric dipole (ED) sideband
      emission. Here, we extend energy-momentum spectroscopy to time-resolved
      measurements, and use this technique to quantify the ED and MD contributions to
      light emission from trivalent chromium doped magnesium oxide (Cr(3+):MgO). This
      allows us to differentiate the MD (2)E -> (4)A2 zero-phonon line from phonon
      assisted (2)E -> (4)A2 and (4)T2 -> (4)A2 ED sidebands. We also demonstrate how
      the relative intensities of the sharp MD zero-phonon line and the broad ED
      sidebands can be used as a qualitative measure of the MD and ED local density of
      optical states. 

PMID- 23879391
TI  - Picazoplatin, an azide-containing platinum(II) derivative for target analysis by
      click chemistry.
AB  - Despite the broad use of platinum-based chemotherapeutics, identification of
      their full range of cellular targets remains a significant challenge. In order to
      identify, visualize, and isolate cellular targets of Pt(II) complexes, we have
      modified the chemotherapeutic drug picoplatin with an azide moiety for subsequent
      click reactivity. The new compound picazoplatin readily binds DNA and RNA
      oligonucleotides and undergoes facile post-labeling click reactions to alkyne
      fluorophore conjugates. Pt-fluorophore click reactions in rRNA purified from drug
      treated Saccharomyces cerevisiae demonstrate its potential for future in vivo
      efforts. 

PMID- 23879392
TI  - Nickel-catalyzed Suzuki-Miyaura couplings in green solvents.
AB  - The nickel-catalyzed Suzuki-Miyaura coupling of aryl halides and phenol-derived
      substrates with aryl boronic acids using green solvents, such as 2-Me-THF and
      tert-amyl alcohol, is reported. This methodology employs the commercially
      available and air-stable precatalyst, NiCl2(PCy3)2, and gives biaryl products in
      synthetically useful to excellent yields. Using this protocol, bis(heterocyclic)
      frameworks can be assembled efficiently. 

PMID- 23879393
TI  - Cytotoxicity of quantum dots used for in vitro cellular labeling: role of QD
      surface ligand, delivery modality, cell type, and direct comparison to organic
      fluorophores.
AB  - Interest in taking advantage of the unique spectral properties of semiconductor
      quantum dots (QDs) has driven their widespread use in biological applications
      such as in vitro cellular labeling/imaging and sensing. Despite their
      demonstrated utility, concerns over the potential toxic effects of QD core
      materials on cellular proliferation and homeostasis have persisted, leaving in
      question the suitability of QDs as alternatives for more traditional fluorescent
      materials (e.g., organic dyes, fluorescent proteins) for in vitro cellular
      applications. Surprisingly, direct comparative studies examining the cytotoxic
      potential of QDs versus these more traditional cellular labeling fluorophores
      remain limited. Here, using CdSe/ZnS (core/shell) QDs as a prototypical assay
      material, we present a comprehensive study in which we characterize the influence
      of QD dose (concentration and incubation time), QD surface capping ligand, and
      delivery modality (peptide or cationic amphiphile transfection reagent) on
      cellular viability in three human cell lines representing various morphological
      lineages (epithelial, endothelial, monocytic). We further compare the effects of
      QD cellular labeling on cellular proliferation relative to those associated with
      a panel of traditionally employed organic cell labeling fluorophores that span a
      broad spectral range. Our results demonstrate the important role played by QD
      dose, capping ligand structure, and delivery agent in modulating cellular
      toxicity. Further, the results show that at the concentrations and time regimes
      required for robust QD-based cellular labeling, the impact of our in-house
      synthesized QD materials on cellular proliferation is comparable to that of six
      commercial cell labeling fluorophores. Cumulatively, our results demonstrate that
      the proper tuning of QD dose, surface ligand, and delivery modality can provide
      robust in vitro cell labeling reagents that exhibit minimal impact on cellular
      viability. 

PMID- 23879394
TI  - Quantifying the trade-off between parameter and model structure uncertainty in
      life cycle impact assessment.
AB  - To enhance the use of quantitative uncertainty assessments in life cycle impact
      assessment practice, we suggest to quantify the trade-off between parameter
      uncertainty, i.e. any uncertainty associated with data and methods used to
      quantify the model parameters, and model structure uncertainty, i.e. the
      uncertainty about the relations and mechanisms being studied. In this paper we
      show the trade-off between the two types of uncertainty in a case of maize
      production with a focus on freshwater ecotoxicity due to pesticide application in
      The Netherlands. Parameter uncertainty in pesticide emissions, chemical-specific
      data, effect and damage data, and fractions of metabolite formation of
      degradation products was statistically quantified via probabilistic simulation,
      i.e. Monte Carlo simulation. Model structure uncertainties regarding the
      concentration-response model to be included, the selection of the damage model,
      and the inclusion of pesticide transformation products were assessed via discrete
      choice analysis. We conclude that to arrive at a minimum level of overall
      uncertainty the linear concentration-response model is preferable, while the
      transformation products may be excluded. Selecting the damage model has a
      relatively low influence on the overall uncertainty. Our study shows that
      quantifying the trade-off between different types of uncertainty can help to
      identify optimal model complexity from an uncertainty point of view. 

PMID- 23879395
TI  - Validity and reliability of an ultrasound system for estimating adipose tissue.
AB  - When health professionals measure the fitness levels of clients, body composition
      is usually estimated. In field settings, body composition is commonly estimated
      with skinfolds or bioelectrical impedance analysis. Recently, a portable
      ultrasound device has been manufactured to estimate what percentage of body mass
      is composed of adipose tissue (AT%). A reported advantage of using ultrasound is
      that inter- and intrarater variations may be minimized when compared with the
      skinfold technique. Therefore, the purpose of this pilot study was twofold; 1) to
      determine the validity of a portable ultrasound device compared with skinfolds
      and 2) determine the reliability of the portable ultrasound device. Participants
      had their measurements taken in the following order: urine specific gravity, body
      mass, height, skinfolds and ultrasound determined. Participants had their urine
      specific gravity and ultrasound determined AT% estimates measured again 48 h
      later. The current pilot study found that the ultrasound was not a valid estimate
      of AT% when compared with the skinfold estimate (TE > 4%). In addition, the 1
      site estimate from the ultrasound was more reliable than the 3-site estimate of
      AT%. These data are of importance to practitioners because it demonstrates that
      while the ultrasound is not a valid estimate compared with skinfolds, the 1-site
      estimate may be able to track changes in AT% over time, making the ultrasound an
      option for assessing changes in body composition.

PMID- 23879396
TI  - End stage renal disease in Brunei Darussalam - report from the first Brunei
      Dialysis Transplant Registry (BDTR).
AB  - The Brunei Dialysis and Transplant Registry (BDTR) was established in 2011 to
      collect data from patients undergoing renal replacement therapy (RRT) in Brunei
      Darussalam. The chief aims of the registry are to obtain general demographic data
      for RRT patients and to determine disease burden attributable to End Stage Renal
      Disease (ESRD). The registry population comprises of all ESRD patients treated in
      Brunei Darussalam. Data domains include general demographic data, medical
      history, ESRD etiological causes, laboratory investigations, dialysis treatment
      and outcomes. There were 545 prevalent RRT patients in Brunei at the end of 2011.
      The incidence and prevalence of ESRD were 265 and 1250 per million population.
      Hemodialysis (HD), Peritoneal Dialysis (PD) and Transplant comprised of 83%, 11%
      and 6% of the RRT population, respectively. Diabetes mellitus accounted for 57%
      of all new incident cases. The mean serum hemoglobin, phosphate, calcium and iPTH
      were 11.0 +/- 1.6 g/dL, 1.9 +/- 0.5 mmol/L, 2.3 +/- 0.2 mmol/L and 202.5 +/-
      323.4 ng/mL. Dialysis adequacy for HD and PD were 65.1 (urea reduction ratio) and
      2.0 +/- 0.3 (Kt/v). 71 % of all prevalent HD had functioning AV fistulae and the
      peritonitis incidence was one in 24.5 patient-month/episode. The first BDTR has
      identified some deficiencies in the renal services in Brunei. However, it signals
      an important milestone for the establishment of benchmarked renal practice in the
      country. We hoped to maintain and improve our registry for years to come and will
      strive to align our standards to acceptable international practice.

PMID- 23879397
TI  - Diagnostic accuracy of glycosylated hemoglobin in chinese patients with
      gestational diabetes mellitus: a meta-analysis based on 2,812 patients and 5,918
      controls.
AB  - BACKGROUND AND AIMS: The accuracy of glycosylated hemoglobin (HBA1c) detection
      for the diagnosis of gestational diabetes mellitus (GDM) has been extensively
      studied in the Chinese population, but the exact role of these detections remains
      controversial. The present meta-analysis was performed to establish the overall
      accuracy of HBA1c for the diagnosis of Chinese patients with GDM. METHODS: After
      a systematic review of related studies, the sensitivity, specificity, positive
      likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio
      (DOR), and other measures about the accuracy of HBA1c in the diagnosis of GDM
      were pooled using random-effects models. The summary receiver operating
      characteristic (SROC) curve analysis was used to summarize the overall test
      performance. RESULTS: Forty-one studies included 2812 Chinese patients with GDM
      and 5918 controls were included in our meta-analysis. The summary estimates for
      HBA1c in the diagnosis of GDM in the studies included were as follows:
      sensitivity 0.762 (95% confidence interval [CI]: 0.746-0.777), specificity 0.917
      (95% CI: 0.910-0.924), PLR 8.21 (95% CI: 3.77-17.89), NLR 0.20 (95% CI: 0.09
      0.44), and DOR 41.40 (95% CI: 11.47-149.38). Our data showed that the SROC curve
      is positioned near the desirable upper left corner of the SROC curve, while the
      area under curve (AUC) was 0.93 with a Q* value of 0.865. CONCLUSIONS:
      Measurement of HBA1c is likely to be a useful diagnostic tool for confirming GDM.
      The results of HBA1c should be interpreted in parallel with clinical findings and
      the results of conventional tests.

PMID- 23879398
TI  - The effect of donor-recipient gender mismatch on short- and long-term graft
      survival in kidney transplantation: a systematic review and meta-analysis.
AB  - BACKGROUND: There is no limitation of gender matching in renal transplantation.
      This study was intended to evaluate its effect on short- and long-term graft
      survival. METHODS: PubMed, the Web of Knowledge, Medline, the Cochrane Library,
      and two additional Chinese databases were searched. The data were then abstracted
      and meta-analyzed. RESULTS: 14 studies involving 445 279 patients were included.
      Each study reported data on the four gender matches (male donor-male recipient,
      MDMR; male donor-female recipient, MDFR; female donor-male recipient, FDMR;
      female donor-female recipient, FDFR). The pooled risk ratios (RRs) for 0.5-, 1-,
      2-, 3-, 5-, and 10-yr graft survival rates showed that the FDMR group had the
      worst outcomes, and when recipients were female, short-term graft survival was
      worse, but long-term graft survival was better. The differences between groups
      changed with time. CONCLUSIONS: FDMR patients showed poor graft survival. The
      female recipients had worse short-term graft survival but the best long-term
      graft survival. This study introduces an important consideration into donor
      recipient matching in renal transplantation.

PMID- 23879399
TI  - Understanding delusion in dementia: a review.
AB  - Alzheimer's disease and other dementia are associated with cognitive and
      functional impairment, as well as neuropsychiatric sequelae, including psychotic
      features. Research has largely concentrated on the study of cognitive decline,
      but the associated behavioral and neuropsychiatric symptoms are of equal
      importance in the clinical profile of the disease. Delusions are common,
      disabling and persistent in the course of dementia. The purpose of the present
      review was to examine the phenomenon of delusion in people with dementia. We
      searched the electronic databases for original research and review articles using
      the search terms "delusion, dementia, Alzheimer's disease, frontotemporal
      dementia, vascular dementia and Lewy body disease". Various types of explanations
      have been proposed regarding the etiology of delusional belief in dementia, and
      cerebral correlates are considered. Pharmacological and non-pharmacological
      treatments are analyzed.

PMID- 23879401
TI  - The bugs within - interdisciplinary approaches to studying host-associated
      microbiota.

PMID- 23879402
TI  - Distinguishing the tremor of Parkinson's disease from essential tremor: finger
      displacement.
AB  - Although, the tremor of Parkinson's disease (PD) usually, but not always, differs
      from essential tremor (ET), there is no simple bedside test to distinguish PD
      from ET. We believe we have made such an observation. We studied 50 consecutive
      tremor-dominant PD patients (mean age: 63.4 years; mean disease duration: 4.9
      years) and 35 consecutive ET patients (mean age: 64.1 years; mean disease
      duration: 12.5 years). Among PD patients, 31 had a bilateral tremor and among ET
      patients, 29 patients had a bilateral tremor. Patients sat opposite the examiner
      and pointed both index fingers at the examiner's index fingers. Then they closed
      their eyes. Within 15 s, one or rarely both of the patient's index fingers moved,
      was displaced, either upward or laterally. Finger displacement occurred only with
      bilateral simultaneous pointing with the patient's eyes closed. All the tremor
      dominant PD patients exhibited displacement of an index finger. In 46 patients,
      it occurred on the side of dominant tremor, in 4, it occurred bilaterally. In 31
      of 35 ET patients, no displacement occurred. In 4 of 35 ET patients, it occurred
      unilaterally on the side of dominant tremor. Odds ratio of distinguishing PD from
      ET: 89.62 at 95% confidence limits (5.31-1513.4), p = 0. 0018. Sensitivity 100%
      (0.91-1), specificity 89% (0.72-0.96). Finger displacement can distinguish the
      tremor of PD from ET. The unilateral movement with eyes closed suggests the
      tremor of PD unlike ET may impact circuits involving the parietal and
      supplementary motor cortices. 

PMID- 23879403
TI  - Quantifying the amount of information available in order to prescribe, dispense
      and administer drugs.

PMID- 23879404
TI  - Time perception in narcolepsy in comparison to patients with Parkinson's disease
      and healthy controls - an exploratory study.
AB  - The striatum and the prefrontal cortex play an important role in cognitive time
      processing, and time perception depends on sustained attention. Narcolepsy
      patients are unable to maintain sustained attention, due probably to deficient
      hypocretin signalling. Impaired time perception has been found in Parkinson's
      disease (PD) and attributed to a dysfunctional dopaminergic striatal pacemaker.
      We aimed to assess time perception in patients with narcolepsy and PD and to
      compare the outcome to healthy control participants. Seventeen narcolepsy
      patients, 12 PD patients and 15 healthy controls performed a short time
      production task, where they had to produce an interval of 1, 2 or 5 s. The
      accuracy of time production differed significantly according to task target
      duration, and there was a trend towards a group difference with narcolepsy
      patients tending to overproduce all target durations. Absolute variability was
      significantly different between groups, with narcolepsy patients showing higher
      absolute variability in comparison to controls and PD patients. The analysis of
      the temporal course of time estimation showed more pronounced overproduction of
      each target duration at the end of each trial in narcolepsy patients, whereas
      performance was more or less stable in controls and PD patients. Overproduction
      and higher variability of all time durations in narcolepsy indicate impaired
      short interval timing in the seconds range, while the scalar property of timing
      was preserved. The time-course of accuracy and variability of time production
      within sessions indicate an attention-related mechanism of impaired interval
      timing. 

PMID- 23879400
TI  - Autophagy: a crucial moderator of redox balance, inflammation, and apoptosis in
      lung disease.
AB  - SIGNIFICANCE: Autophagy is a fundamental cellular process that functions in the
      turnover of subcellular organelles and protein. Activation of autophagy may
      represent a cellular defense against oxidative stress, or related conditions that
      cause accumulation of damaged proteins or organelles. Selective forms of
      autophagy can maintain organelle populations or remove aggregated proteins.
      Autophagy can increase survival during nutrient deficiency and play a
      multifunctional role in host defense, by promoting pathogen clearance and
      modulating innate and adaptive immune responses. RECENT ADVANCES: Autophagy has
      been described as an inducible response to oxidative stress. Once believed to
      represent a random process, recent studies have defined selective mechanisms for
      cargo assimilation into autophagosomes. Such mechanisms may provide for protein
      aggregate detoxification and mitochondrial homeostasis during oxidative stress.
      Although long studied as a cellular phenomenon, recent advances implicate
      autophagy as a component of human diseases. Altered autophagy phenotypes have
      been observed in various human diseases, including lung diseases such as chronic
      obstructive lung disease, cystic fibrosis, pulmonary hypertension, and idiopathic
      pulmonary fibrosis. CRITICAL ISSUES: Although autophagy can represent a pro
      survival process, in particular, during nutrient starvation, its role in disease
      pathogenesis may be multifunctional and complex. The relationship of autophagy to
      programmed cell death pathways is incompletely defined and varies with model
      system. FUTURE DIRECTIONS: Activation or inhibition of autophagy may be used to
      alter the progression of human diseases. Further resolution of the mechanisms by
      which autophagy impacts the initiation and progression of diseases may lead to
      the development of therapeutics specifically targeting this pathway.

PMID- 23879405
TI  - Cutaneous side effects of combined therapy with sorafenib and pegylated
      interferon alpha-2b in metastatic melanoma (phase II DeCOG trial).
AB  - BACKGROUND AND OBJECTIVES: During a clinical study with combined therapy of
      sorafenib and pegylated interferon alpha-2b (SoraPeg study) of the German
      Dermatologic Oncology Group (ADO/DeCOG), multiple and severe cutaneous side
      effects were observed. This study sought to analyze these cutaneous side effects,
      particularly because future studies with combinations of interferon alpha and
      targeted therapies are planned. PATIENTS AND METHODS: In a multicenter phase-II
      DeCOG study (NCT00623402) in 10 dermato-oncology centers, 55 patients with
      metastatic melanoma received a combination of sorafenib (2 x 400 mg/day orally)
      and pegylated interferon alpha-2b (3 MUg/kg body weight 1 x/week subcutaneously).
      All cutaneous side effects were documented. RESULTS: Forty-one patients (74.5 %)
      developed cutaneous side effects, particularly exanthems (51.2 %), hand-foot
      syndrome (36.5 %), alopecia (36.5 %) and pruritus (24.4 %). Due to the cutaneous
      side effects, dose reductions were required in 10 patients, interruption of
      therapy in 10 cases and permanent discontinuation of therapy and in one patient
      with extensive follicular-cystic lesions. Exanthems were seen more frequently in
      women (76.2 %) than in men (23.8 %). The occurrence of cutaneous side effects was
      not correlated with clinical outcome or prognosis. CONCLUSIONS: The combination
      of sorafenib/pegylated interferon alpha-2b caused more cutaneous side effects
      than have been reported for single agents. Despite intensive dermatologic
      management of the cutaneous side effects 24 % of patients required a dose
      modification.

PMID- 23879406
TI  - Comparative studies on acetylcholinesterase characteristics between the aphids,
      Sitobion avenae and Rhopalosiphum padi.
AB  - The aphids Sitobion avenae (Fabricius) and Rhopalosiphum padi (Linnaeus)
      (Hemiptera: Aphidiae) are serious pests on grain crops and usually coexist on
      late period of wheat growth in China. Bioassays showed that R. padi was more
      susceptible than S. avenae to pirimicarb that is used for wheat aphid control,
      and the determination of acetylcholinesterase (AChE, EC 3.1.1.7) sensitivity
      showed that the sensitivity of AChE to pirimicarb was significantly higher in R.
      padi than in S. avenae ( Lu and Gao 2009 ). AChE is the target enzyme of the
      carbamates, including pirimicarb, hence, to understand the mechanism responsible
      for the tolerance difference to carbamate insecticides of S. avenae and R. padi,
      we purified AChE from both aphid species using procainamide affinity column and
      characterized the AChE. The purification factor and yield from S. avenae (234.7
      fold and 92.9%) were far higher than that from R. padi 17.3-fold and 13.9%. The
      results of substrate and inhibitor specificities of purified enzyme from both S.
      avenae and R. padi indicated that the purified enzyme was a typical AChE. The
      crude AChE extract from S. avenae was 5.4-, 4.3- and 8.1-fold less sensitive to
      inhibition by pirimicarb, methomyl and thiodicarb, respectively, than that from
      R. padi, whereas for the purified AChE, S. avenae was only 1.6-, 1.3- and 1.7
      fold less sensitive to inhibition by pirimicarb, methomyl and thiodicarb,
      respectively, than R. padi. This suggests that eserine and BW284C51 may bind with
      other proteins, such as carboxylesterase, in the crude extract to reduce their
      inhibition against AChE. These results are useful for planning the chemical
      control of aphids on wheat.

PMID- 23879407
TI  - Pulmonary rehabilitation after an exacerbation of chronic obstructive pulmonary
      disease - evidence for the applicability of trial results to practice
      populations.

PMID- 23879408
TI  - Tacrolimus trough levels after month 3 as a predictor of acute rejection
      following kidney transplantation: a lesson learned from DeKAF Genomics.
AB  - Most calcineurin inhibitor (CNI)-based protocols reduce blood trough goals
      approximately 2-3 months post-transplant in clinically stable kidney transplant
      recipients. The CNI target trough level to prevent rejection, after reduction, is
      unknown. Using a multivariate Cox proportional hazards model, we determined the
      association of time-varying tacrolimus (TAC) trough levels with acute rejection
      (AR) occurring in the first 6 months post-transplant, but specifically we
      assessed this association after 3 months. A total of 1930 patients received TAC
      based immunosuppression prior to AR in a prospective study. Of the 151 (7.8%) who
      developed AR, 47 developed AR after 3 months post-transplant. In an adjusted time
      varying multivariate model, each 1 ng/ml decrease in TAC trough levels was
      associated with a 7.2% increased risk of AR [hazards ratio (HR) = 1.07, 95%
      confidence interval (CI) (1.01, 1.14) P = 0.03] in the first 6 months. There was
      an additional 23% increased risk of AR with each 1 ng/ml decrease in the TAC
      trough levels in months 3-6 [HR = 1.23, 95% CI (1.06, 1.43) P = 0.008]. In
      conclusion, lower TAC trough levels were significantly associated with increased
      risk of AR in the first 6 months post-transplant with additional risk of AR
      between months 3 and 6 post-transplant. The timing and practice of TAC dose
      reduction should be personalized based on the individual's risk factors. 

PMID- 23879409
TI  - Stochastic Lindemann kinetics for unimolecular gas-phase reactions.
AB  - Lindemann, almost a century ago, proposed a schematic mechanism for unimolecular
      gas-phase reactions. Here, we present a new semiempirical method to calculate the
      effective rate constant in unimolecular gas-phase kinetics through a stochastic
      reformulation of Lindemann kinetics. Considering the rate constants for
      excitation and de-excitation steps in the Lindemann mechanism as temperature
      dependent empirical parameters, we construct and solve a chemical master equation
      for unimolecular gas-phase kinetics. The effective rate constant thus obtained
      shows excellent agreement with experimental data in the entire concentration
      range in which it is reported. The extrapolated values of the effective rate
      constant for very low and very high concentrations of inert gas molecules are in
      close agreement with values obtained using the Troe semiempirical method.
      Stochastic Lindemann kinetics, thus, provides a simple method to construct the
      full falloff curves and can be used as an alternative to the Troe semiempirical
      method of kinetic data analysis for unimolecular gas-phase reactions. 

PMID- 23879410
TI  - Cockroach (Blatella germanica) bites in Amazonian indigenous peoples.

PMID- 23879411
TI  - Using a multi-staged strategy based on machine learning and mathematical modeling
      to predict genotype-phenotype risk patterns in diabetic kidney disease: a
      prospective case-control cohort analysis.
AB  - BACKGROUND: Multi-causality and heterogeneity of phenotypes and genotypes
      characterize complex diseases. In a database with comprehensive collection of
      phenotypes and genotypes, we compared the performance of common machine learning
      methods to generate mathematical models to predict diabetic kidney disease (DKD).
      METHODS: In a prospective cohort of type 2 diabetic patients, we selected 119
      subjects with DKD and 554 without DKD at enrolment and after a median follow-up
      period of 7.8 years for model training, testing and validation using seven
      machine learning methods (partial least square regression, the classification and
      regression tree, the C5.0 decision tree, random forest, naive Bayes
      classification, neural network and support vector machine). We used 17 clinical
      attributes and 70 single nucleotide polymorphisms (SNPs) of 54 candidate genes to
      build different models. The top attributes selected by the best-performing models
      were then used to build models with performance comparable to those using the
      entire dataset. RESULTS: Age, age of diagnosis, systolic blood pressure and
      genetic polymorphisms of uteroglobin and lipid metabolism were selected by most
      methods. Models generated by support vector machine (svmRadial) and random forest
      (cforest) had the best prediction accuracy whereas models derived from naive
      Bayes classifier and partial least squares regression had the least optimal
      performance. Using 10 clinical attributes (systolic and diastolic blood pressure,
      age, age of diagnosis, triglyceride, white blood cell count, total cholesterol,
      waist to hip ratio, LDL cholesterol, and alcohol intake) and 5 genetic attributes
      (UGB G38A, LIPC -514C > T, APOB Thr71Ile, APOC3 3206T > G and APOC3 1100C > T),
      selected most often by SVM and cforest, we were able to build high-performance
      models. CONCLUSIONS: Amongst different machine learning methods, svmRadial and
      cforest had the best performance. Genetic polymorphisms related to inflammation
      and lipid metabolism warrant further investigation for their associations with
      DKD.

PMID- 23879412
TI  - Single-port endo-laparoscopic surgery in combined abdominal procedures.
AB  - Single-port endo-laparoscopic surgery has gained support in the surgical
      community because it is perceived to offer a better postoperative outcome as it
      requires only a single incision. We write this prospective observational study to
      ascertain the feasibility and safety of this technique in patients otherwise
      requiring two operations. Five patients who underwent double procedures with a
      single-port device were reviewed: Case 1, a transabdominal preperitoneal hernia
      repair and gastric wedge resection; Case 2, cholecystectomy and diaphragmatic
      hernia repair; Case 3, oophorectomy and incisional hernia repair; Case 4,
      anterior resection of the rectum and hepatic segmentectomy; and Case 5, left
      adrenalectomy and cholecystectomy. Patient demographics, type of port used,
      operative time, complications and incision length were collected. Mean operative
      time for the cases ranged from 100 to 315 min. Incision length for the single
      port device was 2 cm. In Case 2, an additional 5-mm port was used and an
      intraoperative complication involving a laceration of the liver occurred during
      the suturing of the gallbladder fundus. An additional 8-cm lower abdominal
      incision (Pfannenstiel) was required in Case 4 to complete the colonic
      anastomosis and for specimen retrieval. Single-port endo-laparoscopic surgery is
      a feasible and safe technique for approaching double procedures. It drastically
      reduces the number of scars that a double procedure creates, and if difficulty
      arises, another port can always be added to ease the operation. It can also
      potentially reduce the number of admissions and anesthesia that a patient
      undergoes. 

PMID- 23879413
TI  - Candida albicans colonization on an intragastric balloon.
AB  - Here we present the case of Candida albicans colonization on an intragastric
      balloon placed for weight loss. A 52-year-old obese woman achieved a BMI
      reduction of 10.9 kg/m(2) within 7 months as a result of a BioEnterics
      Intragastric Balloon and a well-balanced, low-calorie diet. During endoscopy for
      balloon removal, the balloon, which was well impacted in the gastric fundus, was
      found to be lime green in color with clusters of cone-shaped cultures on its
      surface. Microbiology assessment revealed the presence of Candida albicans,
      although the patient was totally asymptomatic. 

PMID- 23879414
TI  - Sigmoid volvulus after laparoscopic surgery for sigmoid colon cancer.
AB  - We report the first case of sigmoid volvulus after laparoscopic surgery for
      sigmoid colon cancer. The patient is a 75-year-old man who presented with the
      sudden onset of severe abdominal pain. He had undergone laparoscopic
      sigmoidectomy for cancer 2 years before presentation. CT scan showed a distended
      sigmoid colon with a mesenteric twist, or "whirl sign." Colonoscopy showed a
      mucosal spiral and luminal stenosis with dilated sigmoid colon distally and
      ischemic mucosa. The diagnosis of ischemic colonic necrosis due to sigmoid
      volvulus was established. Resection of the necrotic sigmoid colon was performed
      and a descending colon stoma was created. A long remnant sigmoid colon and
      chronic constipation may contribute to the development of sigmoid volvulus after
      laparoscopic sigmoidectomy. Prompt diagnosis is essential for adequate treatment,
      and colonoscopy aids in the diagnosis of ischemic changes in patients without
      definitive findings of a gangrenous colon. 

PMID- 23879415
TI  - Laparoscopic correction of right transverse colostomy prolapse.
AB  - Colostomy prolapse is a frequently seen complication of transverse colostomy. In
      one child with recurrent stoma prolapse, we performed a loop-to-loop fixation and
      peritoneal tethering laparoscopically. No prolapse had recurred at follow-up.
      Laparoscopic repair of transverse colostomy prolapse seems to be a less invasive
      method than other techniques. 

PMID- 23879416
TI  - Laparoendoscopic single-site concomitant surgery for gallstones and a giant
      ovarian teratoma.
AB  - Laparoendoscopic single-site (LESS) technique has gained popularity in several
      fields of surgery. Our patient had multiple gallstones and a left ovarian mature
      cystic teratoma 12 cm in diameter. She underwent concomitant laparoscopic
      cholecystectomy and adnectomy using LESS technique. Using a transient gasless
      technique resulted in the extraction of a giant ovarian tumor through the
      umbilical incision with no leakage into the abdominal cavity. Concomitant LESS
      surgery is feasible and has many benefits both for patients and doctors -
      cosmetics, possibly less pain, avoidance of multiple surgeries and cost
      effectiveness. LESS technique is also useful for extracting a giant tumor with
      the transient gasless technique. This novel method might be applied to the
      removal of a tumor suspicious for malignancy. 

PMID- 23879417
TI  - Laparoscopic management of giant splenic true cyst with partial splenectomy: a
      case report.
AB  - Non-parasitic splenic cysts are relatively rare, and the optimal surgical
      treatment for them remains controversial. Laparoscopic unroofing is a relatively
      safe and easy technique, but a significant number of recurrences has been
      reported. Thus, complete cystectomy with partial splenectomy is recommended by
      several surgeons. However, patients sometimes suffer from intraoperative
      bleeding. Here, we report a patient with a giant non-parasitic splenic cyst who
      underwent subtotal cystectomy with partial splenectomy. After the dissection of
      the vessels circulating the upper pole at the splenic hilum, the resection line
      of the splenic parenchyma was on the ischemic side of the cyanotic demarcation
      line. A vessel sealing system and laparoscopic coagulation shears were used for
      the resection. We intentionally left about 10% of the cyst wall to avoid bleeding
      from the non-ischemic splenic parenchyma and remaining vessels. No recurrence has
      been detected after 6 months of observation. We believe this method could be a
      useful alternative procedure for the treatment of non-parasitic splenic cysts and
      preservation of the splenic parenchyma. 

PMID- 23879418
TI  - Laparoscopic mesh repair of parahiatal hernia: a case report.
AB  - We report a case of a primary parahiatal hernia that was repaired
      laparoscopically with a composite mesh. A 51-year-old woman presented with
      vomiting and epigastric pain. CT scan showed a giant paraesophageal hernia with
      intrathoracic gastric volvulus. Intraoperatively, a diaphragmatic muscular defect
      was found lateral to an attenuated left crus of the diaphragm, distinct from the
      normal esophageal hiatus. The defect ring was fibrotic, making a tension-free
      primary repair difficult. A laparoscopic mesh repair was performed with a
      composite mesh, which was covered with the hernia sac to prevent potential
      erosion into the esophagus or stomach. Recovery was uneventful and the patient
      was discharged on the 5 days postoperatively. She remained asymptomatic at
      subsequent follow-up. Laparoscopic repair of parahiatal hernia can be safely
      performed. In circumstances where a large or fibrotic defect prevents a tension
      free primary repair, the use of a composite mesh can provide effective repair of
      the hernia. 

PMID- 23879419
TI  - Fractured metallic biliary stent causing obstruction and jejunal perforation.
AB  - Interventional internal drainage of the biliary tract has become an established
      procedure for both the temporary and definitive treatment of biliary obstruction
      due to malignant or benign disease. Biliary stent migration and stent fracture
      are known but rare complications. A 50-year-old man presented with acute onset
      pain in the abdomen and vomiting. He had undergone hepaticojejunostomy following
      a bile duct injury during open cholecystectomy 13 years before he presented at
      our institution. Subsequently, he developed a benign biliary stricture at the
      anastomotic site, which was stented transhepatically by a metallic stent. CT of
      his abdomen showed a fractured stent segment obstructing the jejunum with a
      localized perforation. Herein, we discuss his presentation and course of
      management, and review the factors influencing stent migration and fracture and
      the potential options for stent retrieval. The patient needed surgical
      intervention to retrieve the migrated fragment of metal stent and to resect the
      perforated jejunal segment. The role of endoscopic self-expanding metal stents
      for benign biliary disease remains controversial. A migrated stent that has
      become symptomatic should be removed endoscopically in early and accessible cases
      and surgically when endoscopic measures fail or when complicated by obstruction
      or perforation. 

PMID- 23879420
TI  - Single-incision laparoscopic surgery for giant hepatic cyst.
AB  - INTRODUCTION: The aim of this study was to assess the feasibility and safety of
      single-incision laparoscopic fenestration and to introduce a new surgical
      technique. Laparoscopic fenestration has become a standard approach for
      symptomatic hepatic cysts because of the low recurrence rate and minimal
      postoperative pain. The single-incision laparoscopic surgery (SILS) technique has
      increasingly gained acceptance and is now applied to a variety of organs and
      operations. MATERIALS AND SURGICAL TECHNIQUE: Between February 2010 and March
      2011, we consecutively performed six cases of single-incision laparoscopic
      fenestration. A SILS Port was placed through a single intraumbilical skin
      incision. In addition to standard laparoscopic instruments, a flexible 5-mm
      laparoscope and an articulating grasper were used. The cyst wall was dissected
      with a 5-mm bipolar vessel sealer. SILS was successfully performed in all
      patients, and none required conversion to conventional multiport laparoscopic
      surgery or open surgery. Intraoperative blood loss was minimal in all cases.
      Median operative time was 144 min (range, 100-210 min). All patients were
      discharged uneventfully on 3 day postoperative. Median postoperative follow-up at
      15.5 months (range, 8-20 months) did not reveal any complications or recurrence.
      The umbilical incisions were almost unnoticeable. DISCUSSION: Our findings
      suggest that SILS for fenestration of a giant hepatic cyst is a safe and
      feasible. It is reproducible technique that is comparable to conventional
      laparoscopic surgery.

PMID- 23879421
TI  - Subcutaneoscopic excision of external angular dermoid cyst in children without
      conspicuous scarring.
AB  - INTRODUCTION: External angular dermoid cysts are benign lesions that are excised
      through an incision over the eyebrow. This leaves a visible scar that may not be
      cosmetically acceptable. Herein, we describe a minimally invasive
      subcutaneoscopic technique that involves placing incisions above the hairline to
      avoid scarring on the face. MATERIAL AND SURGICAL TECHNIQUE: This is a
      retrospective review of three consecutive cases of dermoid cysts. Each patient
      underwent subcutaneoscopic excision between March 2012 and September 2012. With
      the patient under general anesthesia, a 6-mm incision was made on the scalp above
      the hairline. After a wide subcutaneous tunnel was created, a 5-mm port with a 30
      degrees  telescope was placed for an optical port. Insufflation was done with CO2
      at pressure of 8 mmHg and flow rate of 1 L/min. Two para-optical stab incisions
      were used to insert a 3-mm Maryland dissector and a 3-mm hook for dissection. The
      cyst was excised and removed through one of the ports. DISCUSSION: All three
      cases underwent successful subcutaneoscopic excision without the need for
      conversion. The mean operative time was 42 min. There were no complications, and
      all patients had excellent cosmesis. Subcutaneoscopic excision of dermoid cyst is
      a technically feasible procedure in pediatric patients, as demonstrated by our
      three cases. It provides excellent cosmesis and avoids scarring on the face.

PMID- 23879422
TI  - Novel technique of cytolithotripsy for large bladder stones.
AB  - INTRODUCTION: We evaluated a minimally invasive surgical technique involving a
      single percutaneous access with a laparoscopic trocar under video-cystoscopic
      vision for managing large bladder stones. All patients were candidates for open
      surgery. MATERIALS AND SURGICAL TECHNIQUE: Fourteen patients with bladder stones
      larger than 3 cm in diameter or multiple stones were treated with this technique.
      The procedure involved the percutaneous placement of a laparoscopic trocar under
      cystoscopic control and the introduction of a rigid nephroscope into the bladder.
      Stones were cleansed via fragmentation or direct removal. DISCUSSION: The
      technique was successful in all cases, resulting in controlled, stone-free
      bladders; there were no surgical complications. The mean operation time was
      comparable to that of standard management. All patients discharged uneventfully.
      None reported urethral stricture during the 24-month follow-up period.
      Percutaneous cystolithotripsy under endoscopic control is easy to perform and
      should be considered as an alternative for large or multiple bladder stones as it
      decreases the risk of urethral stricture.

PMID- 23879423
TI  - Reduced-port laparoscopic surgery for rectal cancer: feasibility based on our
      early experience.
AB  - We report our experience of a reduced-port laparoscopic surgery as an advanced
      laparoscopic surgery for rectal cancer. Twelve selected patients with clinical T1
      2 and N0 rectal cancer (clinical stage I) underwent low anterior resection of the
      rectum. The procedures were performed with one port plus a multiple-instrument
      access port with three channels. The multiple-instrument access port was placed
      at the umbilicus or the site of diverting stoma, and another port was placed in
      the right abdomen or in the opposite abdomen of ostomy. The median operative time
      and intraoperative bleeding were 280 min and 15 mL, respectively. The median
      number of harvested lymph nodes was 20. No major perioperative morbidities
      occurred in this series. The median postoperative hospital stay was 10 days. Low
      anterior resection performed by reduced-port laparoscopic surgery is feasible as
      multiport laparoscopic surgery, and it is a reliable surgical option in selected
      patients with rectal cancer. 

PMID- 23879424
TI  - Laparoscopic management of Spigelian hernias.
AB  - Spigelian hernias, also known as spontaneous lateral ventral hernias, are rare
      primary ventral hernias arising in the Spigelian, or semilunar, line located at
      the lateral border of recti. Because of its varied presentation, clinical
      examination is often inconclusive. Traditional repair of such hernias use the
      open approach. Herein we report on three cases of Spigelian hernias. All were
      diagnosed and treated laparoscopically at our institution between March 2011 and
      June 2012. Multiple surgeons performed the repairs using the laparoscopic
      transabdominal preperitoneal technique of mesh reinforcement and
      reperitonization. There were no perioperative or postoperative complications. All
      three were discharged 1 day postoperatively. A complete resolution of
      preoperative symptoms was observed at follow-up at 1 week, 1 month and 6 months.
      Laparoscopic transabdominal preperitoneal repair of Spigelian hernia is safe,
      easy, and feasible for experienced laparoscopic surgeons. 

PMID- 23879425
TI  - Family functioning, psychosocial stress, and goal attainment in brain injury
      rehabilitation.
AB  - The study investigated the impact of family functioning (as measured by the
      Family Assessment Device) on goal attainment (as measured by a Goal Attainment
      Scale) and psychosocial distress (as measured by the Brief Symptom Inventory-18)
      among survivors of acquired brain injury in a community re-entry rehabilitation
      setting. The bivariate analysis suggests that participants had significantly
      greater goal attainment scores if they were members of families with stronger
      general functioning (r = .27, p < .05), stronger defined family roles (r = .28, p
      < .05), a greater capacity to respond emotionally to each other (r = .29, p <
      .05), and proactively solved family problems (r = .28, p < .05). 

PMID- 23879426
TI  - Israeli employers' hiring intentions for recruiting employees with disabilities:
      how do they compare with US employers?
AB  - Focus groups were used to study differences between Israeli and U.S. nonprofit
      and for-profit employers' hiring intentions of potential employees with
      disabilities. Major differences were found between for-profit and nonprofit
      employers' hiring intentions rather than according to their national affiliation.
      However, U.S. for-profit employers would hire primarily entry-level and seasonal
      employees when market conditions allowed for it. In contrast, their Israeli
      counterparts thought that hiring people with disabilities at subminimum wage was
      an incentive to hire, regardless of the state of the economy. The findings are
      discussed with respect to the applicability of the theory of planned behavior and
      social work practice in the two countries. 

PMID- 23879427
TI  - Structural vulnerability, disability, and access to nongovernmental organization
      services in rural Cambodia.
AB  - Despite the recognition that people with disability are among the poorest and
      most marginalized, breaking the disability-poverty cycle has proven challenging.
      Although UN agencies, most donors, and nongovernmental organizations have
      disability and development policies, many programs perpetuate disability-based
      discrimination. Little research examines why such programs fail to achieve
      sustained livelihood improvement for people with disability. Findings from this
      study that explored the experience of disability in Cambodia suggest that
      programs must explicitly address social and cultural norms and power relations.
      Recommendations for inclusive practice are presented. Listening to the voices of
      people with disability is the crucial first step. 

PMID- 23879428
TI  - Person-centered planning: evidence-based practice, challenges, and potential for
      the 21st century.
AB  - Person-centered planning emerged in the 1990s as an innovative practice to assist
      persons with intellectual and developmental disabilities. The foundational
      purpose of person-centered planning is to assist the individual in developing
      service planning that reflects the needs and desires of the focal person with the
      disability. Despite its popularity with disability practitioners, advocates, and
      policy stakeholders, debate emerged at the beginning of the 21st century as to
      the viability of person-centered planning as an evidence-based practice. This
      article examines the historical development and evidence base, as well as the
      current challenges and potential of person-centered planning for adults with
      intellectual disabilities. 

PMID- 23879429
TI  - Detection and evaluation of elevated lead release from service lines: a field
      study.
AB  - Comparative stagnation sampling conducted in 32 homes in Chicago, Illinois with
      lead service lines demonstrated that the existing regulatory sampling protocol
      under the U.S. Lead and Copper Rule systematically misses the high lead levels
      and potential human exposure. Lead levels measured with sequential sampling were
      highest within the lead service lines, with maximum values more than four times
      higher than Chicago's regulatory compliance results using a first-draw sampling
      protocol. There was significant variability in lead values from different points
      within individual lead service lines and among different lead service line sites
      across the city. Although other factors could also influence lead levels, the
      highest lead results most often were associated with sites having known
      disturbances to the lead service lines. This study underscores the importance and
      interdependence of sample site selection, sampling protocol, and other factors in
      assessing lead levels in a public water system. 

PMID- 23879430
TI  - Conformational stability of OXA-51 beta-lactamase explains its role in carbapenem
      resistance of Acinetobacter baumannii.
AB  - Acinetobacter baumannii, an important nosocomial pathogen, is increasingly
      becoming resistant to antibiotics including recent beta-lactam like imipenem.
      Production of different types of beta-lactamases is one of the major resistance
      mechanisms which bacteria adapt. We recently reported the presence of a beta
      lactamase, OXA-51, in clinical strains of A. baumannii in ICUs of our hospital.
      This study is an attempt to understand the structure-function relationship of
      purified OXA-51 in carbapenem resistance in A. baumannii. The OXA-51 was cloned,
      expressed in E. coli Bl-21(DE3) and further purified. The in vitro enzyme
      activity of purified OXA-51 was confirmed by two independent techniques; in-gel
      assay and spectrophotometric method using nitrocefin. Further in vivo effect of
      OXA-51 was followed by transmission electron microscopy of bacterium. Biophysical
      and biochemical investigations of OXA-51 were done using LC-MS/MS, UV-Vis
      absorption, fluorescence, circular dichroic spectroscopy and isothermal
      calorimetry. Native OXA-51 was characterized as 30.6 kDa, pI 8.43 with no
      disulphide bonds and comprising of 30% alpha-helix, 27% beta-sheet. Secondary
      structure of OXA-51 was significantly unchanged in broad pH (4-10) and
      temperature (30-60  degrees C) range with only local alterations at tertiary
      structural level. Interestingly, enzymatic activity up to 75% was retained under
      above conditions. Hydrolysis of imipenem by OXA-51 (k(m),1 MUM) was found to be
      thermodynamically favourable. In the presence of imipenem, morphology of
      sensitive strain of A. baumannii was drastically changed, while OXA-51
      transformed sensitive strain retained the stable coccobacillus shape, which
      demonstrates that imipenem is able to kill sensitive strain but is unable to do
      so in OXA-51-transformed strain. Hence the production of pH- and temperature
      stable OXA-51 appears to be a major determinant in the resistance mechanisms
      adopted by A. baumannii in order to evade even the latest beta-lactams, imipenem.
      It can be concluded from the study that OXA-51 plays a vital role in the survival
      of the pathogen under stress conditions and thus poses a major threat.

PMID- 23879431
TI  - Structure-efficiency relationship of [1,2,4]triazol-3-ylamines as novel
      nicotinamide isosteres that inhibit tankyrases.
AB  - Tankyrases 1 and 2 are members of the poly(ADP-ribose) polymerase (PARP) family
      of enzymes that modulate Wnt pathway signaling. While amide- and lactam-based
      nicotinamide mimetics that inhibit tankyrase activity, such as XAV939, are well
      known, herein we report the discovery and evaluation of a novel nicotinamide
      isostere that demonstrates selectivity over other PARP family members. We
      demonstrate the utilization of lipophilic efficiency-based structure-efficiency
      relationships (SER) to rapidly drive the evaluation of this series. These efforts
      led to a series of selective, cell-active compounds with solubility,
      physicochemical, and in vitro properties suitable for further optimization. 

PMID- 23879432
TI  - Preparation of fluoroalkenes via the Shapiro reaction: direct access to
      fluorinated peptidomimetics.
AB  - Fluoroalkenes represent a useful class of peptidomimetics with distinct
      biophysical properties. Current preparations of this functional group commonly
      provide mixtures of E- or Z-fluoroalkene diastereomers, and/or mixtures of
      nonfluorinated products. To directly access fluoroalkenes in good
      stereoselectivity, a Shapiro fluorination reaction was developed. Fluoroalkene
      products were accessed in one- or two-step sequences from widely available
      ketones. This strategy should be useful for the preparation of fluorinated
      analogs of peptide-based therapeutics, many of which would be challenging to
      prepare by alternate strategies. 

PMID- 23879433
TI  - A review of alcohol-impaired driving: the role of blood alcohol concentration and
      complexity of the driving task.
AB  - The operation of a motor vehicle requires the integrity of sensory, motor, and
      intellectual faculties. Impairment of these faculties following the consumption
      of alcohol has been studied extensively through laboratory, closed-course and on
      road driving, and epidemiological studies. The scientific literature was reviewed
      critically, with a focus on low-to-moderate blood alcohol concentrations (BAC <=
      0.100%), to identify the most reliable determinants of alcohol-impaired driving.
      Variables such as age, gender, driving skill, and tolerance were shown to have
      limited impact on impairment. It was concluded the most relevant variables are
      BAC and complexity of the driving task. The scientific literature provides a high
      degree of confidence to support the conclusion that a BAC of 0.050% impairs
      faculties required in the operation of a motor vehicle. Whether impairment is
      apparent depends upon the complexity of the driving task, which applies to both
      study design and actual driving. 

PMID- 23879434
TI  - Intestinal epithelial barrier function in liver cirrhosis: an extensive review of
      the literature.
AB  - Recent evidence suggests that translocation of bacteria and bacterial products,
      such as endotoxin from the intestinal lumen into the systemic circulation is a
      contributing factor in the pathogenesis of chronic liver diseases and the
      development of complications in cirrhosis. In addition to alterations in the
      intestinal microbiota and immune system, dysfunction of the intestinal epithelial
      barrier may be an important factor facilitating bacterial translocation. This
      review aims to provide an overview of the current evidence of intestinal
      epithelial barrier dysfunction in human chronic liver diseases and cirrhosis, and
      to discuss possible contributing factors and mechanisms. Data suggest the
      presence of intestinal epithelial barrier dysfunction in patients with chronic
      liver diseases, but are more convincing in patients with cirrhosis, especially in
      those with complications. The barrier dysfunction can result from both direct and
      indirect effects of aetiological factors, such as alcohol and obesity, which can
      cause chronic liver diseases and ultimately cirrhosis. On the other hand
      characteristics of cirrhosis itself, including portal hypertension, alterations
      in the intestinal microbiota, inflammation and oxidative stress can affect
      barrier function of both small and large intestine and may contribute to the
      development of complications. In conclusion, there are indications for intestinal
      epithelial barrier dysfunction in patients with chronic liver diseases and
      especially in patients with cirrhosis, which can be caused by various factors
      affecting both the small and large intestine. 

PMID- 23879436
TI  - The common elements of engagement in children's mental health services: which
      elements for which outcomes?
AB  - Using the distillation component of the Distillation and Matching Model framework
      (Chorpita, Daleiden, & Weisz, 2005 ), we examined which engagement practices were
      associated with three domains of treatment engagement: attendance, adherence, and
      cognitive preparation (e.g., understanding of, readiness for treatment). Eighty
      nine engagement interventions from 40 randomized controlled trials in children' s
      mental health services were coded according to their engagement practices and
      outcomes. Analyses examined whether the practices used in successful
      interventions differed according to engagement domain. Practice patterns differed
      somewhat depending on whether attendance, adherence, or cognitive preparation was
      the outcome of interest. For example, assessment of barriers to treatment
      frequently occurred in successful interventions targeting attendance, whereas
      homework assignment frequently occurred in successful interventions when
      adherence was the target outcome. Modeling and expectation setting were
      frequently used in successful interventions targeting cognitive preparation for
      treatment. Distillation provides a method for examining the practice patterns
      associated with different engagement outcomes. An example of the application of
      these findings to clinical practice includes using certain practices (e.g.,
      assessment, psychoeducation about services, and accessibility promotion) with all
      youth and families to promote attendance, adherence, and cognitive preparation.
      Then, other practices (e.g., modeling, homework assignment) can be added on an as
      needed basis to boost engagement or to address interference in a particular
      engagement domain. The use of a distillation framework promotes a common language
      around engagement and highlights practices that lend themselves well to training,
      thereby promoting the dissemination of engagement interventions. 

PMID- 23879437
TI  - Magnetic/upconversion fluorescent NaGdF4:Yb,Er nanoparticle-based dual-modal
      molecular probes for imaging tiny tumors in vivo.
AB  - Detection of early malignant tumors remains clinically difficult; developing
      ultrasensitive imaging agents is therefore highly demanded. Owing to the unusual
      magnetic and optical properties associated with f-electrons, rare-earth elements
      are very suitable for creating functional materials potentially useful for tumor
      imaging. Nanometer-sized particles offer such a platform with which versatile
      unique properties of the rare-earth elements can be integrated. Yet the
      development of rare-earth nanoparticle-based tumor probes suitable for imaging
      tiny tumors in vivo remains difficult, which challenges not only the physical
      properties of the nanoparticles but also the rationality of the probe design.
      Here we report new approaches for size control synthesis of magnetic/upconversion
      fluorescent NaGdF4:Yb,Er nanocrystals and their applications for imaging tiny
      tumors in vivo. By independently varying F(-):Ln(3+) and Na(+):Ln(3+) ratios, the
      size and shape regulation mechanisms were investigated. By replacing the oleic
      acid ligand with PEG2000 bearing a maleimide group at one end and two phosphate
      groups at the other end, PEGylated NaGdF4:Yb,Er nanoparticles with optimized size
      and upconversion fluorescence were obtained. Accordingly, a dual-modality
      molecular tumor probe was prepared, as a proof of concept, by covalently
      attaching antitumor antibody to PEGylated NaGdF4:Yb,Er nanoparticles through a
      "click" reaction. Systematic investigations on tumor detections, through magnetic
      resonance imaging and upconversion fluorescence imaging, were carried out to
      image intraperitoneal tumors and subcutaneous tumors in vivo. Owing to the
      excellent properties of the molecular probes, tumors smaller than 2 mm was
      successfully imaged in vivo. In addition, pharmacokinetic studies on differently
      sized particles were performed to disclose the particle size dependent
      biodistributions and elimination pathways. 

PMID- 23879438
TI  - Bone mineral density in patients with predialysis chronic kidney disease.
AB  - BACKGROUND: There is limited data available especially in Indian Population about
      prevalence of reduced bone mineral density (BMD) and various factors associated
      with it in CKD patients not on dialysis. MATERIAL: This study included 75 adult
      patients. Patients were divided into three groups depending upon GFR. Serum
      creatinine, albumin, calcium, phosphate (PO4), alkaline phosphatase, iPTH and
      Vitamin D were measured at baseline. BMD was measured by dual energy X-ray
      absorptiometry. RESULTS: There were 51 male and 24 female patients. The mean
      serum phosphate, alkaline phosphatase and iPTH levels increased steadily as CKD
      progressed. On the other hand, mean corrected serum calcium and Vitamin D levels
      decreased progressively in group A, B and C. The mean serum PTH values in group
      A, B and C were 137.16 +/- 109.85, 265.02 +/- 132.03 and 328.14 +/- 119.23 pg/mL,
      respectively and there was significant increase in mean PTH level from group A to
      group C (p < 0.05). The mean level of vitamin D showed a trend of declination
      from group A to C (p < 0.05). Z-score for group A, group B and group C was 1.11
      +/- 2.39, 0.87 +/- 2.66 and -0.92 +/- 1.59, respectively. Similarly, T score for
      the three groups were 0.47 +/- 2.34, -0.4 +/- 2.00 and -1.524 +/- 1.42. Both T
      score and Z-score positively correlated with GFR. There was negative correlation
      between Z-score and iPTH, and positive correlation with Vitamin D. CONCLUSION:
      Reduced bone density was seen early in the course of CKD as estimated from
      reduced BMD levels, increased prevalence of osteoporosis and increased fracture
      risk and it worsened with the progression of CKD.

PMID- 23879439
TI  - Sexual chance taking: a qualitative study on sexuality among detained youths.
AB  - BACKGROUND: Many, although not all, juvenile detainees are known to be sexual
      risk-takers but little attention has been paid to why they engage in early sexual
      intercourse, have more partners, often have sex under the influence of drugs or
      alcohol, and without protection. OBJECTIVE: To understand the rationale behind
      sexual risk-taking among detained adolescents. METHOD: Qualitative study of
      interviews with nine girls and 11 boys, aged 15 to 20 years, at detention centres
      in southern Sweden. RESULTS: Two major categories surface in the analysis of the
      interviews: contradictions and vulnerability. A core category, chance outdoes
      risk that describes the adolescents' pragmatic view on sexual risk-taking as
      being a chance of something good rather than a risk of something bad, captures
      the connection between these categories and the individual. CONCLUSION: Among our
      interviewees, sexual chance taking appears rewarding. Recognising this
      rationality is valuable for all professionals promoting sexual health within
      similar groups of youths.

PMID- 23879440
TI  - An overview of service quality of continuous positive airway pressure services in
      Australian pharmacies.
AB  - BACKGROUND AND OBJECTIVE: Little is known about CPAP services offered in the
      Australian primary care pharmacy setting, despite the potential influence of
      service quality on patient adherence. The objective of this study was to provide
      an overview on a nationwide scale of the range and quality of CPAP and sleep
      apnoea-related services in Australian pharmacies. METHODS: A paper-based
      questionnaire was developed and mailed to all pharmacies in Australia that
      currently provide CPAP services (as identified by manufacturer's distributor
      lists or Internet search). A point system was devised to score participants on
      the quality of their CPAP service. Pharmacies were rated against a list of 23
      criteria that were determined by consensus, with one point allocated for each
      criterion met, allowing for a maximum score of 23. RESULTS: The study response
      rate was 55% (110/199), and representation was obtained from all eight Australian
      states and territories. The mean number of criteria met (total score) for
      pharmacies was 15.7 +/- 3.4 (15.7/23 = 68.3%; score range 2-22). Variability was
      evident in the range of services offered. Eighty-seven per cent of respondents
      believed that pharmacies supplying CPAP should adhere to a formalized set of
      professional guidelines. CONCLUSIONS: The accessibility of pharmacies may make
      them a valuable venue for CPAP service provision. However, models of care to
      guide practice and standardize the variability in services are required.
      Implementation of such models could improve patient access to quality treatment
      in the primary care setting.

PMID- 23879441
TI  - Factors influencing advanced practitioners' ability to enact leadership: a case
      study within Irish healthcare.
AB  - AIM: To report the factors that influence clinical specialists' and advanced
      nurse practitioners' ability to enact their clinical and professional leadership
      roles; findings from the SCAPE study. BACKGROUND: The importance of leadership
      for specialist and advanced practitioners is highlighted in the international
      literature and is considered an important factor in the provision of improved
      patient outcomes. Despite many studies identifying the barriers in developing and
      integrating new specialist/advanced practice roles into health services, little
      is known about the factors that influence the leadership dimension of their role.
      METHOD: A case study design involving 23 clinical specialist/advanced
      practitioners working in Ireland and multidisciplinary team members working with
      them, was used. Data were collected using interview, observation and documentary
      analysis. RESULTS: Four mediating factors influence the specialist/advanced
      practitioner's ability to perform a leadership role, namely the presence of a
      framework for the professional development of the role; opportunities to act as
      leaders; mechanisms for sustaining leadership; and personal attributes of
      practitioners. CONCLUSION AND IMPLICATIONS FOR NURSING MANAGEMENT:
      Nursing/midwifery leaders and managers at all levels have a key role in
      supporting leadership potential, through countering the negative impact of
      professional isolation, expanding opportunities for specialist/advanced
      practitioners to influence policy and network with wider professional groups.

PMID- 23879442
TI  - Pathogenic potential and genetic diversity of environmental and clinical isolates
      of Pseudomonas aeruginosa.
AB  - The aim of this study was to investigate the occurrence of virulence genes among
      clinical and environmental isolates of Pseudomonas aeruginosa and to establish
      their genetic relationships by Enterobacterial Repetitive Intergenic Consensus
      PCR (ERIC-PCR). A total of 60 P. aeruginosa isolates from environmental and
      clinical sources were studied. Of these, 20 bacterial isolates were from soil, 20
      from water, and 20 from patients with cystic fibrosis. Analysis of ERIC-PCR
      demonstrated that the isolates of P. aeruginosa showed a considerable genetic
      variability, regardless of their habitat. Numerous virulence genes were detected
      in both clinical and environmental isolates, reinforcing the possible pathogenic
      potential of soil and water isolates. The results showed that the environmental
      P. aeruginosa has all the apparatus needed to cause disease in humans and
      animals. 

PMID- 23879443
TI  - A retrospective analysis and review of an institution's experience with the
      complications of cranioplasty.
AB  - INTRODUCTION: Cranial reconstruction with a cranioplasty is performed to repair
      skull defects after decompressive craniectomies. AIMS: To retrospectively review
      all cranioplasties performed in our institution over 10 years and analyse the
      complications and the factors that cause complications. PATIENT AND METHODS: Two
      hundred and forty-three cranioplasties were performed from 2000 to 2010, with a
      follow-up of at least 1 year. Age, sex, comorbidities, material, site of skull
      defect, time between decompression and cranioplasty, and rate of complications
      were collected from our database. Fischer's T-test and direct logistical
      regression were performed to identify factors that contributed to the rate of
      complications. p < 0.05 was considered significant. RESULTS: Post-cranioplasty
      seizures (14.81%), infection and exposed implant (9.05%), haemorrhage (1.65%) and
      others (0.82%) were identified complications. Total percentage of complications
      was 25.92%. Previous trauma (p = 0.034) and intracranial haemorrhage (p = 0.019)
      as well as pre-cranioplasty neurological deficit (p = 0.046) were related to
      seizures, while pre-cranioplasty neurological deficit (p = 0.036) and exposed
      implant extrusion (p = 0.048) contributed to infection of cranioplasties.
      DISCUSSION: Most of the seizures may be post-traumatic seizures or scar epilepsy
      from intracranial haemorrhage. Implant extrusions were found to be associated
      with infection of the implant, and they should therefore be treated early.
      Patient selection is important as patients with neurological deficits were
      susceptible to seizures and infection. Intracranial haemorrhage was caused by
      persistant bleeding, trauma or shunt overdrainge. CONCLUSION: Cranioplasty has
      significant complications. A thorough understanding of factors that contribute to
      the different types of complications will benefit the management of cranioplasty
      patients.

PMID- 23879444
TI  - Cognitive performance following spontaneous subarachnoid haemorrhage versus other
      forms of intracranial haemorrhage.
AB  - OBJECTIVE: The exact cause of cognitive deficits following intracranial
      haemorrhage is unclear. This prospective study examines the abilities after
      spontaneous subarachnoid haemorrhage (SAH), intracerebral haemorrhage (ICH) and
      chronic subdural haematoma (SDH) to elucidate the cognitive outcome. PATIENTS AND
      METHODS: Ninety-nine patients with SAH (N = 60), ICH (N = 25), and SDH (N = 14)
      were followed up for an average of 6 and 12 months post-haemorrhage. Cognitive
      tests were used to examine attention, memory, concentration, and executive
      function. Following were used for analysis: 1. the percentage of patients falling
      below the 25th percentile per test, 2. the general development from the first to
      second test point and 3. the incidence of significant changes between the test
      points. Significance was established as p <= 0.05. RESULTS: All three types of
      haemorrhage resulted in deficits as concerns abstract language (53%-75%). The
      processing speed was below the normal levels in more than 70% of the patients
      tested. The cognitive performance of SAH patients was similar to that of patients
      with SDH and ICH patients after 6 months. The number of patients with outcomes
      falling below the 25th percentile (to some extent more than 75% in patients post
      SAH) is high in all patient groups and mostly decreases over the course.
      Nevertheless, patients with SAH reveal improvements in many more areas than with
      ICH and SDH (p <= 0.006). CONCLUSIONS: The cognitive impairments following SAH,
      ICH and SDH deficits appear to develop in a similar way regardless of the type of
      haemorrhage. Cognitive improvement is most pronounced in patients with SAH.

PMID- 23879445
TI  - Supratentorial brain schwannomas: an uncommon location for a common tumour.
AB  - INTRODUCTION: Intracranial schwannomas not related to cranial nerves are uncommon
      brain tumours. Such tumours account for less than 1% of all surgically treated
      schwannomas. Only 79 cases have been reported in the literature. METHODS: We
      describe two cases treated in our centre. The patients are young women with
      seizures as a presenting symptom. Both underwent surgery with the presumptive
      diagnosis of benign brain tumour. Histopathological examination revealed the
      certain diagnosis of Schwannoma. RESULTS: Good outcome was achieved with total
      excision of the tumour. Based on the literature, demographic data, clinical
      aspects, imaging features and theories on the possible origin of this rare tumour
      are discussed. CONCLUSIONS: These tumours should be included in the differential
      diagnosis of supratentorial benign tumours in young adults. Total excision,
      whenever possible, is the treatment of choice.

PMID- 23879446
TI  - Myoclonus associated with concomitant ciprofloxacin and oxycodone in an older
      patient.

PMID- 23879447
TI  - Pigmented lesion of the left nipple in a 49-year-old woman.

PMID- 23879448
TI  - Study of sperm concentration, seminal plasma composition and their physiological
      correlation in the Persian sturgeon, Acipenser persicus.
AB  - The objectives of the present study were to determine ionic and organic
      composition of seminal plasma, sperm concentration and their relationships in the
      Persian sturgeon (Acipenser persicus). In this regard, ionic content (Na(+) ,
      K(+) , Cl(-) , Ca(2+) and Mg(2+) ) and organic content (total protein, glucose,
      cholesterol and triglyceride) along with sperm concentration were measured in 17
      specimens of the Persian sturgeon. The seminal plasma contained 59.53 +/- 2.56
      mm/l sodium, 9.1 +/- 1.42 mm chloride, 4.72 +/- 0.3 mm potassium, 1.45 +/- 0.075
      mm calcium and 0.7 +/- 0.072 mm magnesium. The following organic contents were
      found: total protein 0.11 +/- 0.02 g/dl, glucose 22.18 +/- 4.16 mg/dl,
      cholesterol 6.67 +/- 1.04 mg/dl and triglyceride 15.2 +/- 0.65 mg/dl. The mean
      sperm concentration was estimated to be 1.6 +/- 0.12 (*10(9)  sperm/ml). A
      significant relationship was found between sperm concentration and K(+) of
      seminal plasma (r = 0.533, p < 0.05). Significant correlations were observed
      between ionic contents: Na(+) vs Cl(-) (r = -0.854, p < 0.01) and Mg(2+) vs K(+)
      (-0.583, p < 0.05). Also, level of triglyceride was negatively correlated with
      Mg(2+) (r = -0.503, p < 0.05). Presented data could be considered as a
      complementary study for developing special extenders and protectant solutions for
      improving artificial fertilization in this valuable species. 

PMID- 23879449
TI  - Unusual red shift of the sensor while detecting the presence of Cd2+ in aqueous
      environment.
AB  - A norbornene derived 8-hydroxyquinoline (N8HQ) is designed and synthesized. A
      "turn-on" ratiometric fluorescent response is observed for Cd(2+) in aqueous
      solution upon binding with N8HQ with a characteristic huge red shift of 164 nm. A
      lowest detection limit of 1.6 nM of Cd(2+) is achieved in the presence of other
      heavy metals. 

PMID- 23879450
TI  - Concise NMR approach for molecular dynamics characterizations in organic solids.
AB  - Molecular dynamics characterisations in solids can be carried out selectively
      using dipolar-dephasing experiments. Here we show that the introduction of a sum
      of Lorentzian and Gaussian functions greatly improve fittings of the "intensity
      versus time" data for protonated carbons in dipolar-dephasing experiments. The
      Lorentzian term accounts for remote intra- and intermolecular (1)H-(13)C dipole
      dipole interactions, which vary from one molecule to another or for different
      carbons within the same molecule. Thus, by separating contributions from weak
      remote interactions, more accurate Gaussian decay constants, T(dd), can be
      extracted for directly bonded (1)H-(13)C dipole-dipole interactions.
      Reorientations of the (1)H-(13)C bonds lead to the increase of T(dd), and by
      measuring dipolar-dephasing constants, insight can be gained into dynamics in
      solids. We have demonstrated advantages of the method using comparative dynamics
      studies in the alpha and gamma polymorphs of glycine, cyclic amino acids L
      proline, DL-proline and trans-4-hydroxy-L-proline, the Ala residue in different
      dipeptides, as well as adamantane and hexamethylenetetramine. It was possible to
      distinguish subtle differences in dynamics of different carbon sites within a
      molecule in polymorphs and in L- and DL-forms. The presence of overall molecular
      motions is shown to lead to particularly large differences in dipolar-dephasing
      experiments. The differences in dynamics can be attributed to differences in
      noncovalent interactions. In the case of hexamethylenetetramine, for example, the
      presence of C-H...N interactions leads to nearly rigid molecules. Overall, the
      method allows one to gain insight into the role of noncovalent interactions in
      solids and their influence on the molecular dynamics.

PMID- 23879451
TI  - Size variability of handwriting in healthy Korean older adults.
AB  - AIM: The aim of the present study was to delineate how age-related deterioration
      affects the handwriting of healthy elderly (HE) subjects. METHODS: A total of 235
      HE (54 males, 181 females) aged 57-91 years participated as subjects in the
      study. In order to compare the area of handwriting, we divided the participants
      into two groups: (i) aged 57-74 years; and (ii) aged 75-91 years. The writing
      stimulus was a four-syllabic word with one-to-one grapheme-to-phoneme
      correspondence. The size of each syllable in the target word was measured using a
      software program. Alignment of the word to baseline was assessed using a multiple
      choice checklist. RESULTS: As compared with handwriting by the younger group, the
      older group showed greater variability in the size of the written syllables
      within the word (P = 0.023). CONCLUSION: The handwriting was characterized by
      unequal size among syllables and non-perpendicular alignment, which could be
      explained by several factors. First, the variability might have resulted from
      irregular fine movement motor control in older adults. Second, the deterioration
      of visual feedback and visuomotor integration in normal aging might have affected
      handwriting performance. In conclusion, variability of handwriting can be
      sensitive in predicting the aging process.

PMID- 23879452
TI  - Primary Epstein-Barr virus infection with polyradiculitis: a case report.
AB  - BACKGROUND: Nervous system complications of primary Epstein-Barr virus (EBV)
      infection in adults are rare, but may occur with encephalitis, meningitis,
      myelitis, cranial and peripheral neuropathies, or radiculitis. CASE PRESENTATION:
      We describe an immune competent adult with a primary EBV infection complicated by
      lumbosacral polyradiculitis with pure radicular pain. Prior to the onset of
      radicular pain the 35-year-old woman had been suffering from infectious
      mononucleosis misdiagnosed for streptococcal tonsillitis. The diagnosis of
      primary EBV infection associated polyradiculitis was proven by serology and PCR
      in serum and CSF. Under initially started empiric therapy with intravenous
      acyclovir and analgesics the patient completely recovered within a few days.
      CONCLUSION: This case report highlights that EBV should be taken into
      consideration in the diagnostic work up of radicular pain syndromes, even in
      immune competent adults. There is no approved causal therapy for EBV infections.
      In accordance with our case, observations based on a few patients with EBV and
      nervous system involvement suggest, that acyclovir treatment might be associated
      a with better course. However, prospective randomized controlled trials
      addressing the question of the effectiveness of acyclovir in patients with
      primary EBV infection and neurological complications are lacking.

PMID- 23879453
TI  - Potential danger of hair dyes marketed as free from para-phenylenediamine.

PMID- 23879455
TI  - Multiple dermatofibromas in Down syndrome.

PMID- 23879456
TI  - Joinpoint regression analysis of female breast cancer mortality in Serbia 1991
      2010.
AB  - The aim of this descriptive epidemiologic study was to analyze the mortality
      trends of female breast cancer in Serbia (excluding Kosovo and Metohia) from 1991
      to 2010. Average annual percentage of change and the corresponding 95% confidence
      interval (CI) was computed for trend using linear models assuming a Poisson
      distribution. The Serbian female population showed an increase in breast cancer
      mortality continuously from 1991 to 2010 (average annual percentage of change = +
      0.9, 95% CI = 0.6-1.1). Breast cancer mortality declined in women aged 30-49
      years but increased in women >=50 years old. Decline in breast cancer mortality
      in young women was observed during the entire period and was significant in those
      35-49 years old. In women 50-54 years old, a significant increase in breast
      cancer mortality during the period 1991-1997 was followed by significant decrease
      until 2010. In all older age groups, mortality rates significantly increased
      during all periods observed. The only exception was among women aged 65-69 years
      old in whom a small, non-significant decrease in breast cancer mortality was
      observed in the period 1991-1998, followed by significant increase until 2010.
      According to a comparability test, breast cancer mortality trends in 30-49, 50
      69, and 70+ year age groups differed significantly (p < 0.01). 

PMID- 23879457
TI  - The association between women's self-rated health and satisfaction with
      environmental services in an underserved community in Lebanon.
AB  - This research evaluated the association between women's self-rated health and a
      number of socioeconomic and environmental health indicators relating to drinking
      water services in an underserved Lebanese community. A population-based, cross
      sectional survey using interviews was adopted to obtain information from female
      homemakers of 2,223 households in the town of Bebnine, Lebanon. The questionnaire
      included indicators on self-rated health, satisfaction with water quality, source
      of drinking water, occurrence of diarrhea, and socioeconomic variables, such as
      education, occupation, and perceived economic status. Self-rated health was
      categorized as poor, fair, and good. Odds ratios for poor and fair compared to
      good self-rated health values were calculated using multinomial logistic
      regression. A total of 712 women (32%) reported poor self-rated health. Women who
      perceived their household income to be worse than others in town were four times
      as likely to report poor health. Compared to women who were satisfied with
      drinking water quality, dissatisfied women were 42% more likely to report poor
      health. Women living in households reporting recent episodes of diarrheal illness
      had poorer health ratings than those without. The findings suggest a positive
      relationship between individual perceptions of water quality and self-rated
      health. Community concerns over their surrounding environment serve as a primary
      guide for infrastructural development and government policy. 

PMID- 23879454
TI  - Complex of the herpes simplex virus type 1 origin binding protein UL9 with DNA as
      a platform for the design of a new type of antiviral drugs.
AB  - The herpes simplex virus type 1 origin-binding protein, OBP, is a DNA helicase
      encoded by the UL9 gene. The protein binds in a sequence-specific manner to the
      viral origins of replication, two OriS sites and one OriL site. In order to
      search for efficient inhibitors of the OBP activity, we have obtained a
      recombinant origin-binding protein expressed in Escherichia coli cells. The UL9
      gene has been amplified by PCR and inserted into a modified plasmid pET14 between
      NdeI and KpnI sites. The recombinant protein binds to Box I and Box II sequences
      and possesses helicase and ATPase activities. In the presence of ATP and viral
      protein ICP8 (single-strand DNA-binding protein), the initiator protein induces
      unwinding of the minimal OriS duplex (~80 bp). The protein also binds to a single
      stranded DNA (OriS*) containing a stable Box I-Box III hairpin and an unstable AT
      rich hairpin at the 3'-end. In the present work, new minor groove binding ligands
      have been synthesized which are capable to inhibit the development of virus
      induced cytopathic effect in cultured Vero cells. Studies on binding of these
      compounds to DNA and synthetic oligonucleotides have been performed by
      fluorescence methods, gel mobility shift analysis and footprinting assays.
      Footprinting studies have revealed that Pt-bis-netropsin and related molecules
      exhibit preferences for binding to the AT-spacer in OriS. The drugs stabilize
      structure of the AT-rich region and inhibit the fluctuation opening of AT-base
      pairs which is a prerequisite to unwinding of DNA by OBP. Kinetics of ATP
      dependent unwinding of OriS in the presence and absence of netropsin derivatives
      have been studied by measuring the efficiency of Forster resonance energy
      transfer (FRET) between fluorophores attached to 5'- and 3'- ends of an
      oligonucleotide in the minimal OriS duplex. The results are consistent with the
      suggestion that OBP is the DNA Holiday junction (HJ) binding helicase. The
      protein induces conformation changes (bending and partial melting) of OriS
      duplexes and stimulates HJ formation in the absence of ATP. The antiviral
      activity of bis-netropsins is coupled with their ability to inhibit the
      fluctuation opening of AT base pairs in the A + T cluster and their capacity to
      stabilize the structure of the AT-rich hairpin in the single-stranded
      oligonucleotide corresponding to the upper chain in the minimal duplex OriS. The
      antiviral activities of bis-netropsins in cell culture and their therapeutic
      effects on HSV1-infected laboratory animals have been studied.

PMID- 23879458
TI  - Sources of breast and cervical cancer information for Hmong women and men.
AB  - Despite low breast and cervical cancer screening levels among Hmong women in the
      United States reported in the literature, understanding of the barriers to
      screening for Hmong women is limited. Health literacy issues may influence
      screening behavior for this population. This qualitative study explored sources
      of information about breast and cervical cancer, including screening, and
      identified barriers to seeking such information for Hmong women and men.
      Researchers conducted semi-structured, in-depth interviews with 84 Hmong women
      and men living in Oregon. Interviews were audio-recorded and transcribed.
      Transcripts of 83 usable interviews were analyzed using content analysis. Health
      care providers and the Internet were the most frequently cited sources of
      information about breast and cervical cancer, including screening. Other sources
      were family, friends, and other media. Over half of the participants indicated
      that nothing would prevent them from seeking information about these topics.
      These findings suggested that health care providers and the Internet may be
      important sources of information about breast and cervical cancer screening for
      Hmong women. Additional research is needed to examine further Hmong women's
      health literacy needs and preferences with regards to breast and cervical cancer
      screening. 

PMID- 23879459
TI  - Postpartum substance use and depressive symptoms: a review.
AB  - National survey data suggest that new mothers have high prevalences of alcohol
      and illicit drug use. Depression correlates with substance use, and new mothers
      with postpartum depression may be at high risk for substance use. Understanding
      postpartum substance use and its relationship to postpartum depression can inform
      future research and intervention. A literature search was conducted resulting in
      12 studies published from 1999-2012 examining postpartum alcohol use, drug use,
      or combined postpartum depression and substance use. Postpartum alcohol
      (prevalence range 30.1%-49%) and drug use (4.5%-8.5%) were lower than use among
      not pregnant, not postpartum women (41.5%-57.5%, 7.6%-10.6%, respectively) but
      higher than use among pregnant women (5.4%-11.6%, 3.7%-4.3%, respectively).
      Correlates of postpartum problem drinking were being unemployed, unmarried, and a
      cigarette smoker. Prevalence of drug use was highest among white new mothers,
      followed by blacks and Hispanics, but black new mothers appeared at greater risk
      of drug use. No identified studies examined correlates of postpartum drug use
      beyond race/ethnicity. Postpartum depressive symptoms were prevalent among
      postpartum substance users and those with a substance use history (19.7%-46%).
      The postpartum period is a critical time. Prevalent substance use and the
      scarcity of studies warrant research to identify means to reduce maternal
      substance use. 

PMID- 23879460
TI  - Culture and sun exposure in immigrant East Asian women living in Australia.
AB  - In this qualitative study, researchers examined cultural and attitudinal factors
      that might be related to sun-exposure behaviors among East Asian women living in
      Australia. Researchers asked Chinese (n = 20) and Korean (n = 16) immigrant women
      who participated in a larger cross-sectional quantitative study of vitamin D
      blood levels to volunteer to participate in an in-depth interview in 2010. These
      women reported a number of cultural factors related to their attitudes and
      behaviors with regard to sun exposure. They expressed preference for fair skin, a
      tradition of covering skin when outdoors, and no sunbathing culture. They
      believed that fair skin was more beautiful than tanned skin. They reported that
      beauty was the reason for active avoidance of sunlight exposure. Although they
      reported knowledge of the need for sun avoidance due to skin cancer risk, few
      reported knowledge about the benefits of sun exposure for adequate vitamin D
      levels. These findings may provide some reasons for vitamin D deficiency
      previously reported in these populations. Thus, researchers recommend that these
      attitudes of excessive sun protection and limiting sun exposure be further
      investigated as they may have implications for planning and delivery of health
      promotion programs to this growing population of immigrants in Australia. 

PMID- 23879462
TI  - Alitretinoin: an effective treatment option for pagetoid reticulosis.

PMID- 23879461
TI  - Views and experiences of suicidal ideation during pregnancy and the postpartum:
      findings from interviews with maternal care clinic patients.
AB  - INTRODUCTION: Perinatal suicidality (i.e., thoughts of death, suicide attempts,
      or self-harm during the period immediately before and up to 12 months after the
      birth of a child) is a significant public health concern. Few investigations have
      examined the patients' own views and experiences of maternal suicidal ideation.
      METHODS: Between April and October 2010, researchers identified 14 patient
      participants at a single university-based medical center for a follow-up, semi
      structured interview if they screened positive for suicidal ideation on the
      Patient Health Questionnaire-9 (PHQ-9) short form. In-depth interviews followed a
      semi-structured interview guide. Researchers transcribed all interviews verbatim
      and analyzed transcripts using thematic network analysis. RESULTS: Participants
      described the experience of suicidality during pregnancy as related to somatic
      symptoms, past diagnoses, infanticide, family psychiatric history (e.g.,
      completed suicides and family member attempts), and pregnancy complications. The
      network of themes included the perinatal experience, patient descriptions of
      changes in mood symptoms, illustrations of situational coping, and reported
      mental health service use. IMPLICATIONS: The interview themes suggested that in
      this small sample, pregnancy represented a critical time period to screen for
      suicide and to establish treatment for the mothers in the study. These findings
      may assist health care professionals in the development of interventions designed
      to identify, assess, and prevent suicidality among perinatal women.

PMID- 23879464
TI  - beta-Arabinofuranosylation using 5-O-(2-quinolinecarbonyl) substituted ethyl
      thioglycoside donors.
AB  - A new beta-stereoselective D- and L-arabinofuranosylation method has been
      developed employing 5-O-(2-quinolinecarbonyl) substituted arabinosyl ethyl
      thioglycosides as glycosyl donors. The approach allows a wide range of acceptor
      substrates to be used; the beta-selectivity is good-to-excellent. Stereoselective
      synthesis of a mannose-capped octasaccharide portion from a mycobacterial cell
      wall polysaccharide was then carried out to demonstrate the utility of this
      methodology.

PMID- 23879463
TI  - A medicinal chemistry perspective for targeting histone H3 lysine-79
      methyltransferase DOT1L.
AB  - Histone H3 lysine79 (H3K79) methyltransferase DOT1L plays an important role in
      the activation and maintenance of gene transcription. It is essential for
      embryonic development as well as normal functions of the hematopoietic system,
      heart, and kidney in adults. DOT1L has been found to be a drug target for acute
      leukemia with mixed lineage leukemia (MLL) gene translocations. The rearranged
      onco-MLL can recruit DOT1L, causing aberrant H3K79 methylation, overexpression of
      leukemia relevant genes, and eventually leukemogenesis. Potent DOT1L inhibitors
      possess selective activity against this type of leukemia in cell-based and animal
      studies, with the most advanced compound being in clinical trials. In the
      medicinal chemistry point of view, we review the biochemistry, cancer biology,
      and current inhibitors of DOT1L, as well as biophysical (including X-ray
      crystallographic) investigation of DOT1L-inhibitor interactions. Potential future
      directions in the context of drug discovery and development targeting DOT1L are
      discussed. 

PMID- 23879465
TI  - Successful tunneled catheter placement in a hemodialysis patient with idiopathic
      multiple central venous stenoses.
AB  - Central venous stenosis (CVS) in hemodialysis patients could be secondary to
      central venous catheterization, high flow arteriovenous fistula, as well as
      extrinsic compression. However, we report a senile hemodialysis patient of left
      internal jugular vein stenosis and right innominate vein occlusion unrelated to
      any known risk factors. Aided by computed tomography and digital subtraction
      angiography, we managed to dilate the stenosis by percutaneous balloon
      angioplasty, followed by successful tunneled catheter placement. Nephrologists
      should be aware of idiopathic CVS and its impact on the creation and preservation
      of vascular access. When confronted with difficulties in catheter placement,
      practitioners need to consider the possibilities of idiopathic CVS and refer to
      radiological tests. 

PMID- 23879466
TI  - Dynamics of ninhydrin-reactive nitrogen and pH in gravesoil during the extended
      postmortem interval.
AB  - Estimating the postmortem interval of skeletal remains is difficult, as few tools
      exist to do so. To address this problem, we conducted a field experiment to
      measure the chemistry of swine (Sus scrofa domesticus Linnaeus) gravesoil after 1
      year and 3 years postmortem. Carcasses were placed on the soil surface of a
      pasture during June in a cold (Dfa) climate. Significant (p < 0.05) increases in
      ninhydrin-reactive nitrogen, pH, total nitrogen, and nitrate in gravesoil were
      detected 1 year postmortem. Significant differences in gravesoil chemistry were
      not detected 3 years postmortem. These observations coincided with gaps in plant
      growth 1 year postmortem and the development of lush vegetation 3 years
      postmortem. We conclude that these phenomena can be used to assist the decision
      making process regarding the allocation of resources during the early stages of a
      death investigation. 

PMID- 23879467
TI  - Rat substrains differ in the magnitude of spontaneous locomotor recovery and in
      the development of mechanical hypersensitivity after experimental spinal cord
      injury.
AB  - A number of different rodent experimental models of spinal cord injury have been
      used in an attempt to model the pathophysiology of human spinal cord injury. As a
      result, interlaboratory comparisons of the outcome measures can be difficult.
      Further complicating interexperiment comparisons is the fact that the rodent
      response to different experimental models is strain-dependent. Moreover, the
      literature is abundant with examples in which the same injury model and strain
      result in divergent functional outcomes. The objective of this research was to
      determine whether substrain differences influence functional outcome in
      experimental spinal cord injury. We induced mild contusion spinal cord injuries
      in three substrains of Sprague-Dawley rats purchased from three different
      European breeders (Scanbur, Charles River, and Harlan) and evaluated the impact
      of injury on spontaneous locomotor function, hypersensitivity to mechanical
      stimulation, and bladder function. We found that Harlan rats regained
      significantly more hindlimb function than Charles River and Scanbur rats. We also
      observed substrain differences in the recovery of the ability to empty the
      bladder and development of hypersensitivity to mechanical stimulation. The Harlan
      substrain did not show any signs of hypersensitivity in contrast to the Scanbur
      and Charles River substrains, which both showed transient reduction in paw
      withdrawal thresholds. Lastly, we found histological differences possibly
      explaining the observed behavioral differences. We conclude that in spite of
      being the same strain, there might be genetic differences that can influence
      outcome measures in experimental studies of spinal cord injury of Sprague-Dawley
      rats from different vendors.

PMID- 23879468
TI  - Nurse willingness to report for work in the event of an earthquake in Israel.
AB  - AIM: To examine variables affecting nurse willingness to report for work in the
      event of an earthquake in Israel and whether this can be predicted through the
      Theory of Self-Efficacy. BACKGROUND: The nursing profession has a major role in
      preparing for earthquakes. Nurse willingness to report to work in the event of an
      earthquake has never before been examined. METHOD: Self-administered
      questionnaires were distributed among a convenience sample of 400 nurses and
      nursing students in Israel during January-April 2012. RESULTS: High willingness
      to report to work in the event of an earthquake was declared by 57% of
      respondents. High perceived self-efficacy, level of knowledge and experience
      predict willingness to report to work in the event of an earthquake.
      Multidisciplinary collaboration and support was also cited as a meaningful
      factor. CONCLUSION: Perceived self-efficacy, level of knowledge, experience and
      the support of a multidisciplinary staff affect nurse willingness to report to
      work in the event of an earthquake. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse
      managers can identify factors that increase nurse willingness to report to work
      in the event of an earthquake and consequently develop strategies for more
      efficient management of their nursing workforce.

PMID- 23879469
TI  - Meniscus-mask lithography for narrow graphene nanoribbons.
AB  - Described here is a planar top-down method for the fabrication of precisely
      positioned very narrow (sub-10 nm), high aspect ratio (>2000) graphene
      nanoribbons (GNRs) from graphene sheets, which we call meniscus-mask lithography
      (MML). The method does not require demanding high-resolution lithography tools.
      The mechanism involves masking by atmospheric water adsorbed at the edge of the
      lithography pattern written on top of the target material. The GNR electronic
      properties depend on the graphene etching method, with argon reactive ion etching
      yielding remarkably consistent results. The influence of the most common
      substrates (Si/SiO2 and boron nitride) on the electronic properties of GNRs is
      demonstrated. The technique is also shown to be applicable for fabrication of
      narrow metallic wires, underscoring the generality of MML for narrow features on
      diverse materials. 

PMID- 23879470
TI  - Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee
      on Diabetes and Cancer.
AB  - In recent years, diabetes has been shown to be associated with cancer risk, and
      this has led to a joint committee being formed, enlisting experts from the Japan
      Diabetes Society and the Japanese Cancer Association to address this issue.
      Epidemiological data in Japan provides evidence to demonstrate that diabetes is
      associated with increased risk for cancers, especially colorectal, liver, and
      pancreatic cancers. The mechanisms through which diabetes is assumed to promote
      oncogenesis include insulin resistance and associated hyperinsulinemia,
      hyperglycemia, and inflammation. Common risk factors for type 2 diabetes and
      cancer include aging, male sex, obesity, physical inactivity, inappropriate diet
      (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber
      intake), excessive alcohol drinking, and smoking. Given that inappropriate
      diet/exercise, smoking and excessive alcohol drinking are common risk factors for
      diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol
      moderation may be associated with decreased risk for cancer in diabetic patients.
      There is as yet limited evidence as to whether any particular antidiabetic agents
      may influence cancer risk. 

PMID- 23879473
TI  - Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in
      the rats with hypercholesterolemia.
AB  - OBJECTIVE: The objective of this study is to evaluate the effect and mechanism of
      mitochondria-targeted peptides (MTP131 and SPI20) on contrast-induced acute
      kidney injury (CI-AKI) in rats with hypercholesterolemia. METHOD: Forty SD rats
      were randomly divided into normal diet group (NN, n = 8) and high cholesterol
      supplemented dietary group (HN, n = 32). At the end of 8 weeks, the group HN was
      divided into four subgroups. All Rats were given injection of either diatrizoate
      (10 mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or
      SPI20 were given injection with MTP131 or SPI 20 (3 mg/kg) by peritoneal cavity
      for 3 times. Blood, urine and renal tissue samples were prepared to determine
      biochemical parameters. The renal pathological changes were evaluated by
      hematoxylin and eosin staining and scored semiquantitatively, The protein
      expression of renal NOX4 was also measured by Western blotting. RESULTS: In
      diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium
      (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal
      malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of
      NOX4 in kidney tissue were significantly increased (p < 0.01). In the groups
      pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and
      NADPH oxidase activity in renal tissue decreased (p < 0.01), the levels of renal
      super oxygen dehydrogenises and ATPase activity increased (p < 0.01). The renal
      injuries induced by contrast media (CM) were alleviated. CONCLUSION: MTP131 and
      SPI20 might protect acute kidney injury induced by CM in rats with
      hypercholesterolemia.

PMID- 23879474
TI  - Differentiating anxiety and depression in children and adolescents: evidence from
      event-related brain potentials.
AB  - The current study, which was a reanalysis of previous data, focused on the error
      related negativity (ERN)-an event-related potential (ERP) associated with error
      monitoring-and the feedback negativity (FN)-an ERP associated with reward
      processing. Two objectives motivated this study: first, to illustrate the
      relationship between the ERN and anxious symptoms, and the relationship between
      the FN and depressive symptoms; second, to explore whether the ERN and the FN
      relate uniquely to anxiety and depression, respectively, in children. EEG was
      collected from twenty-five 11- to 13-year-old participants (12 female; 23
      Caucasian, 1 Asian, 1 of Caucasian and Hispanic ethnicity) during tasks designed
      to elicit an ERN and an FN. Participants and a parent completed questionnaires
      assessing the participant's anxious and depressive symptomatology. Increasing
      anxiety was related to a larger ERN, and increasing depression was related to a
      smaller FN. Further analysis demonstrated that these relationships remained
      significant when controlling for the contribution of other variables; that is,
      the ERN continued to predict anxiety when controlling for the FN and depression,
      and the FN continued to predict depression when controlling for the ERN and
      anxiety. Thus, in late childhood and early adolescence, the ERN and the FN appear
      to relate uniquely to anxious and depressive symptoms, respectively. Although
      this research is still in early stages, the ERN and the FN have the potential to
      inform trajectories of risk for anxiety and depression, and could be utilized in
      clinical settings as cost- and labor-efficient neural biomarkers. 

PMID- 23879475
TI  - Photooxidation of arsenite under 254 nm irradiation with a quantum yield higher
      than unity.
AB  - Arsenite (As(III)) in water was demonstrated to be efficiently oxidized to
      arsenate (As(V)) under 254 nm UV irradiation without needing any chemical
      reagents. Although the molar absorption coefficient of As(III) at 254 nm is very
      low (2.49 +/- 0.1 M(-1)cm(-1)), the photooxidation proceeded with a quantum yield
      over 1.0, which implies a chain of propagating oxidation cycles. The rate of
      As(III) photooxidation was highly enhanced in the presence of dissolved oxygen,
      which can be ascribed to its dual role as an electron acceptor of photoexcited
      As(III) and a precursor of oxidizing radicals. The in situ production of H2O2 was
      observed during the photooxidation of As(III) and its subsequent photolysis under
      UV irradiation produced OH radicals. The addition of tert-butyl alcohol as OH
      radical scavenger significantly reduced (but not completely inhibited) the
      oxidation rate, which indicates that OH radicals as well as superoxide serve as
      an oxidant of As(III). Superoxide, H2O2, and OH radicals were all in situ
      generated from the irradiated solution of As(III) in the presence of dissolved O2
      and their subsequent reactions with As(III) induce the regeneration of some
      oxidants, which makes the overall quantum yield higher than 1. The homogeneous
      photolysis of arsenite under 254 nm irradiation can be also proposed as a new
      method of generating OH radicals. 

PMID- 23879476
TI  - Percentage of ubiquitinated spermatozoa does not correlate with fertilizing
      capacity of thawed bovine semen.
AB  - In the spermatozoa of some species, the ubiquitin-proteasome system detects
      altered proteins and tags them for elimination by the proteasome. In some
      species' ejaculates, a high proportion of ubiquitinated spermatozoa (i.e. those
      having ubiquitin bound to the altered or damaged membrane proteins) has been
      related to infertility. The aim of this study was to assess whether the
      percentage of ubiquitinated spermatozoa relates to fertility of dairy bulls and
      whether ubiquitination increases during protein remodelling that occurs during in
      vitro spermatic capacitation. Thirty-two frozen semen straws from four high
      fertility (ReproMax((r)) ) and four normal-fertility (Normal) Holstein-Friesian
      sires were evaluated. Ubiquitinated and capacitated spermatozoa were quantified
      by sperm ubiquitin tag immunoassay and chlortetracycline stain, respectively.
      Fertilizing capacity of sires was assessed by in vitro fertilization. No
      differences were found between Normal and ReproMax((r)) sires with regard to the
      observed percentage of ubiquitinated spermatozoa (42.97 +/- 3.69% and 49.68 +/-
      9.27%, respectively; p > 0.05). Additionally, no differences were found in the
      percentage of ubiquitinated spermatozoa as a consequence of spermatic
      capacitation in either Normal (42.97 +/- 3.69% before capacitation vs 44.67 +/-
      7.5% after; p > 0.05) or ReproMax((r)) sires (49.68 +/- 9.27% before vs 45.05 +/-
      7.51% after; p > 0.05). The percentage of ubiquitinated spermatozoa in a thawed
      sperm samples did not correlate with its in vitro fertilizing capacity; thus,
      this assay does not prove useful to detect in vivo fertility differences between
      sires. Additionally, protein degradation occurring during remodelling of the
      spermatozoon plasma membrane during the capacitation process does not seem to
      involve the ubiquitin-proteasome system. 

PMID- 23879477
TI  - A randomized trial comparing diode laser enucleation of the prostate with
      plasmakinetic enucleation and resection of the prostate for the treatment of
      benign prostatic hyperplasia.
AB  - PURPOSE: We compared the safety and efficacy of diode laser enucleation of the
      prostate (DiLEP) with plasmakinetic enucleation and resection of the prostate
      (PKERP). PATIENTS AND METHODS: A total of 80 patients with bladder outflow
      obstruction from benign prostatic hyperplasia (BPH) were randomly assigned to
      either DiLEP or PKERP prospectively. All patients were assessed preoperatively
      and followed up at 3, 6, and 12 months postoperatively. Baseline characteristics
      of the patients, perioperative data, and postoperative outcomes were compared.
      The operative data and perioperative and postoperative complications were also
      recorded. RESULTS: The preoperative data were comparable between the two groups.
      The DiLEP group had significantly shorter operative time, postoperative
      irrigation, time and catheterization time than the PKERP group (P=0.000, P=0.000
      and P=0.000). The drop in hemoglobin level was statistically significantly less
      in the DiLEP group (P=0.002). There were no statistical differences in
      complications between the two groups except irritative symptoms (P=0.018). At the
      3, 6, and 12-month follow-up, no statistically significant differences were
      observed between the two groups in International Prostate Symptom Score, maximum
      flow rate, quality of life, postvoid residual, prostate volume, and prostate
      specific antigen level (P>0.05). CONCLUSIONS: The efficacy of DiLEP and PKERP
      were similar for relieving obstruction and low urinary tract symptoms. DiLEP
      provides less risk of hemorrhage, reduced bladder irrigation, and catheter times.
      The downward morcellation technique is more efficient than the resection
      technique. Future well designed randomized trials with extended follow-up and
      larger sample sizes may be needed to better verify the advantage of DiLEP in
      treating patients with symptomatic BPH.

PMID- 23879478
TI  - The expression of fatty acid metabolism-associated proteins is correlated with
      the prognosis of meningiomas.
AB  - The expression of fatty acid metabolism-associated proteins is correlated with
      the prognosis of meningiomas. Meningioma is a common tumor of the nervous system;
      however, reliable prognostic markers for meningioma are currently insufficient.
      High fatty acid synthase (FAS) expression occurs in many tumors, and is
      associated with tumor progression and grade. Few studies have previously
      investigated fatty acid metabolism in meningioma; thus, in this study, we
      investigated the expression of FAS and brain fatty acid-binding protein (BFABP)
      proteins in all grades of meningioma and determined the association to meningioma
      grade, invasiveness, recurrence, and progression. We determined expression levels
      of FAS and BFABP in all grade meningiomas by immunohistochemical analysis in 314
      patients diagnosed with meningioma. The expression levels of FAS and BFABP
      increased significantly in correlation with meningioma grade (p < 0.01). Compared
      with benign meningioma, the expression levels of FAS and BFABP were significantly
      higher in brain invasive meningioma (p < 0.01). Compared with nonrecurrent
      meningioma (benign meningioma), the expression of FAS was also increased in
      recurrent meningioma (p < 0.01). The expression of fatty acid metabolism
      associated proteins potentially correlates with meningioma grade, invasiveness,
      aggressiveness, and recurrent status and provides evidence for a novel
      therapeutic target for meningioma.

PMID- 23879479
TI  - Relationship between tissue hydroxyl radical and oxidatively modified
      macromolecule levels.
AB  - AIMS: The relationship between hydroxyl radical (.OH) and oxidatively modified
      macromolecule formations was examined in tissues from young and aged mice.
      METHODS: To determine the .OH generation in tissues in vivo using the
      hydroxylation trapping reaction of .OH into salicylic acid (SA), analytical
      conditions for dihydroxybenzoic acid (DHBA) and SA determination, and optimum
      dosages of SA for administration and time-points of tissue sampling were
      determined. 2, 3-DHBA levels in tissues from young mice and age-related changes
      were determined with the oxidatively modified macromolecules. RESULTS: 2, 3-DHBA,
      a hydroxylation compound of SA, is considered to be suitable for determination of
      .OH levels in tissues. Tissue levels of 2, 3-DHBA expressed as a molar ratio to
      SA, was comparable among tissues, and was in accordance with 8-oxo-2'
      deoxyguanosine (8-oxodG) and carbonylated proteins. In the aging process, 2, 3
      DHBA levels in the brain and heart increased in the biphasic pattern in
      accordance with the 8-oxodG and thiobarbituric acid reactive substances (TBARS)
      levels, whereas levels of carbonylated proteins were not changed with age.
      CONCLUSIONS: An in vivo method for .OH measurement using hydroxylation of SA was
      optimized. However, as a limitation, 2, 3-DHBA, as well as other oxidative stress
      markers, could be affected by various in vivo factors. The accordance was seen
      among 2, 3-DHBA, 8-oxodG and carbonylated protein levels in tissues from young
      mice. The tissue levels of 2, 3-DHBA increased in accordance with the 8-oxodG and
      TBARS during the aging process.

PMID- 23879480
TI  - The entropic nature of protein thermal stabilization.
AB  - We performed thermodynamic analysis of temperature-induced unfolding of
      mesophilic and thermophilic proteins. It was shown that the variability in
      protein thermostability associated with pH-dependent unfolding or linked to the
      substitution of amino acid residues on the protein surface is evidence of the
      governing role of the entropy factor. Numerical values of conformational
      components in enthalpy, entropy and free energy which characterize protein
      unfolding in the "gas phase" were obtained. Based on the calculated absolute
      values of entropy and free energy, a model of protein unfolding is proposed in
      which the driving force is the conformational entropy of native protein, as an
      energy of the heat motion (T.S(NC)) increasing with temperature and acting as an
      factor devaluating the energy of intramolecular weak bonds in the transition
      state. 

PMID- 23879481
TI  - Interprofessional education in community-based Alzheimer's disease diagnosis and
      treatment.
AB  - As the population ages and understanding of Alzheimer's disease (AD) improves,
      the number of older adults diagnosed and treated for AD and related dementias is
      projected to increase. Dementia diagnosis, treatment and patient and family
      education are complex processes best done through collaboration among healthcare
      professions. The educational program described in this article aimed to create an
      interprofessional team approach to the diagnosis and treatment of dementia
      involving medical and family nurse practitioner students. A two-group
      treatment/control pretest posttest design was used to measure changes in
      knowledge, attitudes and appreciation for an interprofessional team approach to
      patient care. Findings from this interprofessional program demonstrated that
      nurse practitioner students gained higher levels of knowledge regarding AD, and
      medical students gained more positive attitudes toward these patients and their
      caregivers. Comments from students indicated that both medical and nursing
      students found the experience valuable. Understanding the roles that various
      providers play will help healthcare professional meet the challenge of caring for
      the increasing number of patients with memory loss and for their families.

PMID- 23879484
TI  - Fewer mixed signals, more green salad.

PMID- 23879483
TI  - Prognostic impact of serum CYFRA 21-1 in patients with advanced lung
      adenocarcinoma: a retrospective study.
AB  - BACKGROUND: Serum CYFRA 21-1 is one of the most important serum markers in the
      diagnosis of non-small cell lung cancer (NSCLC), especially squamous-cell
      carcinoma. However, it remains unknown whether pretreatment serum CYFRA 21-1
      values (PCV) may also have prognostic implications in patients with advanced lung
      adenocarcinoma. METHODS: We retrospectively reviewed the data of 284 patients
      (pts) who were diagnosed as having advanced lung adenocarcinoma and had received
      initial therapy. RESULTS: Of the study subjects, 121 pts (43%) had activating
      epidermal growth factor receptor (EGFR) mutations (Mt+), while the remaining 163
      pts (57%) had wild-type EGFR (Mt-). Univariate analysis identified gender (male/
      female), ECOG performance status (PS) (0-1/ >=2), PCV (<2.2 ng/ml/ >=2.2 ng/ml),
      EGFR mutation status (Mt+/ Mt-), pretreatment serum CEA values (<5.0 ng/ml/ >=5.0
      ng/ml), smoking history (yes/ no) and EGFR-TKI treatment (yes/ no) as prognostic
      factors (p = .008, p < .0001, p < .0001, p < .0001, p = .036, p = .0012, p <
      .0001 respectively). Cox's multivariate regression analysis identified PCV <
      2.2ng/ml as the only factor significantly associated with prolonged survival (p <
      .0001, hazard ratio: 0.43, 95% CI 0.31-0.59), after adjustments for PS (p <
      .0001), EGFR mutation status (p = .0069), date of start of initial therapy (p =
      .07), gender (p = .75), serum CEA level (p = .63), smoking history (p = .39) and
      EGFR-TKI treatment (p = .20). Furthermore, pts with Mt+ and PCV of <2.2 ng/ml had
      a more favorable prognosis than those with Mt+ and PCV of >=2.2 ng/ml (MST: 67.0
      vs. 21.0 months, p < .0001), and patients with Mt- and PCV of <2.2 ng/ml had a
      more favorable prognosis than those with Mt- and PCV of >=2.2 ng/ml (MST: 24.1
      vs. 10.2 months, p < .0001). CONCLUSION: PCV may be a potential independent
      prognostic factor in both Mt+ and Mt- patients with advanced lung adenocarcinoma.

PMID- 23879485
TI  - How can we improve access to new (and old) antibiotics in Australia?

PMID- 23879486
TI  - Should we screen for lung cancer in Australia?

PMID- 23879487
TI  - International treatment guidelines for anaemia in chronic kidney disease - what
      has changed?

PMID- 23879490
TI  - Regulation and the prevention agenda.

PMID- 23879491
TI  - A funding model for public-good clinical trials.

PMID- 23879492
TI  - Subacute care funding in the firing line.

PMID- 23879493
TI  - What makes a same-sex parented family?

PMID- 23879494
TI  - Doctors in support of law reform for voluntary euthanasia.

PMID- 23879495
TI  - Doctors in support of law reform for voluntary euthanasia.

PMID- 23879496
TI  - Doctors in support of law reform for voluntary euthanasia. Reply.

PMID- 23879497
TI  - Rethinking psychotropics in nursing homes.

PMID- 23879498
TI  - Rethinking psychotropics in nursing homes.

PMID- 23879499
TI  - Rethinking psychotropics in nursing homes. Reply.

PMID- 23879500
TI  - Seeking asylum: health and human rights in Australia.

PMID- 23879501
TI  - Arthroscopy to treat osteoarthritis of the knee?

PMID- 23879502
TI  - Arthroscopy to treat osteoarthritis of the knee?

PMID- 23879503
TI  - Restless legs syndrome and day procedures.

PMID- 23879504
TI  - Global health training and postgraduate medical education in Australia: the case
      for greater integration.

PMID- 23879505
TI  - Global health training and postgraduate medical education in Australia: the case
      for greater integration.

PMID- 23879506
TI  - Global health training and postgraduate medical education in Australia: the case
      for greater integration. Reply.

PMID- 23879508
TI  - Initial outcomes of using allografts from donation after cardiac death donors for
      liver transplantation in New South Wales.
AB  - OBJECTIVES: To report the early outcomes of the initial selection and use of
      donation after cardiac death (DCD) donor livers for transplantation in New South
      Wales, following a guidelines implementation process. DESIGN AND SETTING: Review
      of database and medical records from the Australian National Liver
      Transplantation Unit and the NSW Organ and T2 Donation Service for DCD activity
      including organ donor offers and retrievals, from 1 July 2007 to 31 December
      2010. MAIN OUTCOME MEASURES: Acceptance and utilisation rates of livers from DCD
      donors, and patient and graft outcomes after liver transplantation. RESULTS: Of
      the potential 84 DCD donor offers, 45 were declined, and 15 of the 39 attempted
      retrievals provided livers for transplantation. The most common reason for non
      retrieval of the liver was the time to declaration of death exceeding 30 minutes
      after withdrawal of treatment (14 donors), followed by abnormality in the donor
      liver (eight donors). Data on early outcomes for liver transplant recipients
      showed a median peak aspartate aminotransferase of 3667 U/L (range, 919-11 264
      U/L), but no delayed graft function. Four patients developed biliary
      complications (two within 3 months and two later). Patient and graft survival
      were 100% at a median follow-up of 15 months. CONCLUSIONS: As a result of the re
      establishment of multiorgan donation through the DCD pathway, 15 (18%) of the
      selected DCD donors provided livers for transplantation. Patient and graft
      survival rates were excellent, and the rate of intra- and postoperative
      complications was acceptable. Hence, the selective transplantation of DCD donor
      liver allografts will continue to be pursued and the outcomes followed.

PMID- 23879509
TI  - Risk factors for erectile dysfunction in a cohort of 108 477 Australian men.
AB  - OBJECTIVES: To quantify relationships between erectile dysfunction (ED), ageing
      and health and lifestyle factors for men aged 45 years and older. DESIGN: Cross
      sectional, population-based study seeking data on health, sociodemographic and
      lifestyle factors by questionnaire (the 45 and Up Study). PARTICIPANTS AND
      SETTING: 108 477 men aged 45 years or older, living in New South Wales, and
      recruited into the 45 and Up Study between 10 January 2006 and 17 February 2010.
      MAIN OUTCOME MEASURES: Self-reported ED. RESULTS: In the 101 674 men reporting no
      prior diagnosis of prostate cancer, 39.31% (95% CI, 39.01%-39.61%) had no ED,
      25.14% (95% CI, 24.87%-25.40%) had mild ED (ie, experienced ED sometimes), 18.79%
      (95% CI, 18.55%-19.03%) had moderate (ie, usually experienced) ED and 16.77% (95%
      CI, 16.55%-17.00%) had complete ED. After adjusting for sociodemographic
      characteristics, the odds of moderate/complete ED increased by 11.30% (OR, 1.11;
      95% CI, 1.11-1.12) each year from the age of 45 years. Overall, the risk of
      moderate/complete ED was higher among men with low socioeconomic status, high
      body mass index, those who were sedentary, current smokers and those with
      diseases including diabetes, heart disease, and depression/anxiety, compared with
      men without these risk factors. Moderate alcohol consumption was associated with
      a significantly reduced risk of ED in men aged 45-54 years, but not in older men.
      Almost all men aged 75 or older reported moderate/severe ED; however, increased
      physical activity was associated with a lower odds of ED in this group.
      CONCLUSIONS: In a large population-based cross-sectional study, ED increased
      considerably with age. There are a range of potentially modifiable risk factors
      for ED, including smoking, low physical activity, and high body mass index.

PMID- 23879510
TI  - Birthweight and fasting glucose and insulin levels: results from the Aboriginal
      Birth Cohort Study.
AB  - OBJECTIVE: To examine the relationships between birthweight, current size, and
      fasting glucose and fasting insulin levels in Aboriginal adolescents. DESIGN,
      PARTICIPANTS AND SETTING: Longitudinal prospective study of a Northern Territory
      Aboriginal birth cohort of 686 Aboriginal babies born at the Royal Darwin
      Hospital between January 1987 and March 1990, and followed up between December
      2006 and January 2008 in over 40 NT locations. MAIN OUTCOME MEASURES: Fasting
      insulin and glucose levels, adjusted for gestational age, sex and contemporary
      age. RESULTS: Among the 134 participants with complete data, those with fetal
      growth restriction (FGR) or low birthweight (LBW) at birth were not overweight at
      18 2013s. In these circumstances, birthweight showed a significant positively
      directed association with fasting glucose levels (P = 0.002). Current weight
      showed a significant and positively directed association with both fasting
      insulin (P < 0.001) and fasting glucose levels (P = 0.001), and current height
      showed a significant and positively directed association with insulin levels (P =
      0.006). CONCLUSIONS: Birthweight was only positively associated with fasting
      glucose levels, with no association with fasting insulin levels. The high-risk
      combination for type 2 diabetes of LBW or FGR with later overweight or obesity
      was rare in this adolescent Aboriginal population.

PMID- 23879511
TI  - A description of human hydatid disease in Tasmania in the post-eradication era.
AB  - OBJECTIVE: To describe human hydatid disease in Tasmania since 1996, the 2013
      that the state was declared provisionally hydatid-free. DESIGN, SETTING AND
      PARTICIPANTS: Individuals with a new diagnosis or history of hydatid disease
      between January 1996 and July 2012 were identified through a number of sources
      including public health notifications, discharge coding from Tasmanian public
      hospitals, and the Royal Hobart Hospital pathology laboratory information system.
      Individuals were included if they fulfilled the case definition. Details
      regarding their diagnosis, management and risk factors were obtained by
      interview, review of medical notes, or both. The information was collected and
      analysed over a 3-month period from 30 July 2012 to 30 October 2012. MAIN OUTCOME
      MEASURES: Patient demographics, site of infection, details of hydatid disease
      management and outcomes, time and place of likely hydatid acquisition, and public
      health notification. RESULTS: Fifty-one patients were identified, of whom 41 met
      the case definition. Twenty-five represented new diagnoses between 1996 and 2012.
      Median age was 71 2013s (range, 44-99 2013s). There were 21 women and 20 men.
      Thirty-eight patients had hepatic disease, five of whom had at least one other
      site involved. Four had extra-abdominal disease. Twenty-nine patients could be
      assessed for possible time and place of hydatid acquisition and all had
      significant risk factors for hydatid acquisition before 1980. Ten of the 25
      patients diagnosed between 1996 and 2012 had been notified to the Tasmanian
      Department of Health and Human Services. CONCLUSION: We found no evidence of
      transmission of hydatid disease to humans following the provisional declaration
      of eradication of hydatid disease.

PMID- 23879512
TI  - Everolimus treatment of abdominal lymphangioleiomyoma in five women with sporadic
      lymphangioleiomyomatosis.
AB  - OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare systemic disease of young
      women arising from mutations in the tuberous sclerosis complex (TSC) genes, TSC1
      or TSC2. This disrupts the mammalian target of rapamycin (mTOR) pathway,
      affecting cellular proliferation and growth. mTOR inhibitors are a promising
      novel therapy in LAM. The mTOR inhibitor sirolimus is reported to produce
      resolution of lymphatic abnormalities in LAM, but the efficiacy of the mTOR
      inhibitor everolimus has not been assessed. We aimed to examine the efficacy of
      everolimus on lymphatic abnormalities in LAM. DESIGN, SETTING AND PARTICIPANTS:
      Open-label treatment of five patients with sporadic LAM (sLAM) and abdominopelvic
      and lung involvement at the outpatient LAM clinic of a tertiary city teaching
      hospital. Clinical data were collected during treatment of the women and included
      regular clinical reviews, everolimus levels, lung function and computed
      tomography assessment before and after 6 months of everolimus treatment. MAIN
      OUTCOME MEASURES: Symptoms and level of resolution of lymphangioleiomyomas.
      RESULTS: All five women experienced significant shrinkage or complete resolution
      of the lymphangioleiomyomas during treatment. In one woman, cessation of
      everolimus resulted in recurrence of symptoms. Adverse events were compatible
      with the known side-effect profile of everolimus, but overall the drug was well
      tolerated. CONCLUSIONS: This is the first report to suggest that everolimus has
      efficacy in the treatment of lymphangioleiomyoma and chylous ascites in sLAM.

PMID- 23879513
TI  - Mercury poisoning from home gold amalgam extraction.

PMID- 23879514
TI  - Access to the Commonwealth electoral roll for medical research.
AB  - In the 2010-11 financial 2013, there was a dramatic reduction in the approvals
      granted by the Australian Electoral Commission for access to samples of the adult
      population derived from the electoral roll for the purposes of public health
      research. Much time and effort has been expended in making applications without
      success. Researchers refused access to electoral roll samples must rely on
      sampling methods that are not as robust and that may produce less reliable data.
      We outline a set of recommendations that, if adopted, will result in a fairer
      system for obtaining access to the electoral roll for public health research.

PMID- 23879515
TI  - MJA Dr Eric Dark Creative Writing Prize - Enough?

PMID- 23879516
TI  - MJA Dr Eric Dark Creative Writing Prize - Esther.

PMID- 23879517
TI  - Internship: a journey of wrong turns and coloured forms.

PMID- 23879518
TI  - Unsuspected varicella-zoster infection complicating mucosal-dominant pemphigus
      vulgaris.

PMID- 23879519
TI  - Do patients with mild to moderate psoriasis really have a sedentary lifestyle?
AB  - The aim of this study was to compare aerobic exercise capacity, daily physical
      activity, pulmonary functions, resting metabolic rate, and body composition
      parameters in patients with psoriasis and healthy controls. A total of 60
      participants (30 [15 men, 15 women] patients with psoriasis, and 30 [15 men, 15
      women] healthy controls) ranging in age from 22-57 were included in the study.
      Maximal aerobic capacity was determined by Astrand exercise protocol. Daily
      physical activity was measured with an accelerometer. Resting metabolic rate was
      determined with an indirect calorimeter. Pulmonary function tests were performed
      with a portable spirometer. Body composition was established with a bioelectric
      impedance analysis system. Skinfold thicknesses and body circumference
      measurements were carried out. Short Form 36 quality of life questionnaire was
      applied to all participants. In both genders, daily physical activity parameters
      were found to be higher in the psoriasis group compared to the control. Maximal
      aerobic capacity, resting metabolic rate, pulmonary function tests, body fatness,
      body fat distributions, and quality of life were not statistically different
      between patients with psoriasis and controls in males and females. We suggest
      that patients with psoriasis who do not have psoriatic arthritis or severe
      psoriasis are well in performing daily physical activities. In addition, we
      suggest that this lifestyle helped to prevent impairments of body fatness, body
      fat distributions, resting metabolic rate, pulmonary functions, and quality of
      life in patients with mild to moderate psoriasis. 

PMID- 23879520
TI  - PTP1B: a simple enzyme for a complex world.
AB  - Our understanding of the fundamental regulatory roles that tyrosine phosphatases
      play within cells has advanced significantly in the last two decades. Out-dated
      ideas that tyrosine phosphatases acts solely as the "off" switch counterbalancing
      the action of tyrosine kinases has proved to be flawed. PTP1B is the most
      characterized of all the tyrosine phosphatases and it acts as a critical negative
      and positive regulator of numerous signaling cascades. PTP1B's direct regulation
      of the insulin and the leptin receptors makes it an ideal therapeutic target for
      type II diabetes and obesity. Moreover, the last decade has also seen several
      reports establishing PTP1B as key player in cancer serving as both tumor
      suppressor and tumor promoter depending on the cellular context. Despite many key
      advances in these fields one largely ignored area is what role PTP1B may play in
      the modulation of immune signaling. The important recognition that PTP1B is a
      major negative regulator of Janus kinase - signal transducer and activator of
      transcription (JAK-STAT) signaling throughout evolution places it as a key link
      between metabolic diseases and inflammation, as well as a unique regulator
      between immune response and cancer. This review looks at the emergence of PTP1B
      through evolution, and then explore at the cell and systemic levels how it is
      controlled physiologically. The second half of the review will focus on the
      role(s) PTP1B can play in disease and in particular its involvement in metabolic
      syndromes and cancer. Finally we will briefly examine several novel directions in
      the development of PTP1B pharmacological inhibitors.

PMID- 23879521
TI  - Early detection of paracetamol toxicity using circulating liver microRNA and
      markers of cell necrosis.

PMID- 23879522
TI  - Citrate-induced aggregation of conjugated polyelectrolytes for Al(3+)-ion-sensing
      assays.
AB  - This work shows the sodium citrate induced efficient interpolymer pi-stacking
      aggregation of the planar cationic conjugated polyelectrolyte poly[{9,9-bis[6'
      (N,N-trimethylamino)hexyl]-2,7-fluorenyleneethynylene}-alt-co-(1,4-phenylene)]
      dibromide (PFE) in aqueous solution, which results in the self-quenching of
      fluorescence. Using the citrate-induced aggregation properties of PFE and the
      strong chelation ability of citrate with aluminum ions (Al(3+)), a sensitive and
      selective Al(3+)-ion detection assay in aqueous solution was developed through
      monitoring of the fluorescence recovery of PFE. The fluorescence intensity
      recovery of PFE depends on the concentration of Al(3+) ions, and linear
      fluorescence recovery was observed in the range of 0.5-9 MUM. The limit of
      detection of this assay is 0.37 MUM. Its simplicity and rapidity mean this assay
      shows promise for the real-time detection of Al(3+). 

PMID- 23879523
TI  - A brucellosis disease control strategy for the Kakheti region of the country of
      Georgia: an agent-based model.
AB  - Brucellosis has been reported in livestock and humans in the country of Georgia
      with Brucella melitensis as the most common species causing disease. Georgia
      lacked sufficient data to assess effectiveness of the various potential control
      measures utilizing a reliable population-based simulation model of animal-to
      human transmission of this infection. Therefore, an agent-based model was built
      using data from previous studies to evaluate the effect of an animal-level
      infection control programme on human incidence and sheep flock and cattle herd
      prevalence of brucellosis in the Kakheti region of Georgia. This model simulated
      the patterns of interaction of human-animal workers, sheep flocks and cattle
      herds with various infection control measures and returned population-based data.
      The model simulates the use of control measures needed for herd and flock
      prevalence to fall below 2%. As per the model output, shepherds had the greatest
      disease reduction as a result of the infection control programme. Cattle had the
      greatest influence on the incidence of human disease. Control strategies should
      include all susceptible animal species, sheep and cattle, identify the species of
      brucellosis present in the cattle population and should be conducted at the
      municipality level. This approach can be considered as a model to other countries
      and regions when assessment of control strategies is needed but data are
      scattered. 

PMID- 23879524
TI  - A clinically relevant accuracy study of computer-planned implant placement in the
      edentulous maxilla using mucosa-supported surgical templates.
AB  - PURPOSE: The purpose of the study is to determine the clinically relevant
      accuracy of implant placement in the edentulous maxilla using computer planning
      and a mucosa-supported surgical template. MATERIALS AND METHODS: In each of in
      total 30 consecutive edentulous patients suffering from retention problems of
      their upper denture, two or four Branemark MkIII Groovy (Nobel Biocare(r),
      Zurich, Switzerland) implants in the maxilla were installed. Preoperatively,
      first, a cone-beam computer tomography (cone beam computer tomography) scan was
      acquired, followed by virtual implant planning. Hereafter, a surgical template
      was designed to allow flapless implant placement using the template as a guide.
      To inventory the accuracy of implant placement, a postoperative CBCT scan was
      obtained and matched to the preoperative scan. The accuracy of implant placement
      was validated three-dimensionally. The Implant Position Orthogonal Projection
      validation method was applied to measure the clinically relevant implant
      deviations (i.e., in both the bucco-lingual and mesio-distal plane). Also, the
      influence of type of surgery, use of fixation pins, and position on the dental
      arch were investigated with regard to implant deviations. RESULTS: In total, 104
      implants were installed. In bucco-lingual direction, a mean implant deviation of
      0.67 mm was scored at the implant tip, of 0.51 mm at the shoulder, of -0.83 mm in
      depth, as also a mean deviation of angulation of 1.74 degrees . In mesio-distal
      direction, a mean implant deviation of 0.75 mm was found at the implant tip, of
      0.60 mm at the implant shoulder, of -0.75 mm in depth, and a deviation of
      angulation of 1.94 degrees . Of all implants, 74% was placed not deep enough
      compared with the planning. Implant position on the dental arch, the use of
      fixation pins, and type of surgery showed no significant effect on implant
      deviations. However, a significant difference for implant deviations in both
      buccal and mesial direction was observed, explained by a nonoptimal positioning
      of the surgical template. CONCLUSIONS: Computer-aided implant planning showed to
      be a clinically relevant tool for the placement of two or four implants in the
      maxilla of fully edentulous patients. Exact positioning of the surgical template
      in anterior/posterior direction is crucial in reducing implant deviations both in
      buccal and mesial direction.

PMID- 23879526
TI  - Information-theoretical assessment of the performance of likelihood ratio
      computation methods.
AB  - Performance of likelihood ratio (LR) methods for evidence evaluation has been
      represented in the past using, for example, Tippett plots. We propose empirical
      cross-entropy (ECE) plots as a metric of accuracy based on the statistical theory
      of proper scoring rules, interpretable as information given by the evidence
      according to information theory, which quantify calibration of LR values. We
      present results with a case example using a glass database from real casework,
      comparing performance with both Tippett and ECE plots. We conclude that ECE plots
      allow clearer comparisons of LR methods than previous metrics, allowing a
      theoretical criterion to determine whether a given method should be used for
      evidence evaluation or not, which is an improvement over Tippett plots. A set of
      recommendations for the use of the proposed methodology by practitioners is also
      given.

PMID- 23879525
TI  - Structure of NADP(+)-dependent glutamate dehydrogenase from Escherichia coli-
      reflections on the basis of coenzyme specificity in the family of glutamate
      dehydrogenases.
AB  - Glutamate dehydrogenases (GDHs; EC 1.4.1.2-4) catalyse the oxidative deamination
      of L-glutamate to alpha-ketoglutarate, using NAD(+) and/or NADP(+) as a cofactor.
      Subunits of homo-hexameric bacterial enzymes comprise a substrate-binding domain
      I followed by a nucleotide-binding domain II. The reaction occurs in a catalytic
      cleft between the two domains. Although conserved residues in the nucleotide
      binding domains of various dehydrogenases have been linked to cofactor
      preferences, the structural basis for specificity in the GDH family remains
      poorly understood. Here, the refined crystal structure of Escherichia coli GDH in
      the absence of reactants is described at 2.5-A resolution. Modelling of NADP(+)
      in domain II reveals the potential contribution of positively charged residues
      from a neighbouring alpha-helical hairpin to phosphate recognition. In addition,
      a serine that follows the P7 aspartate is presumed to form a hydrogen bond with
      the 2'-phosphate. Mutagenesis and kinetic analysis confirms the importance of
      these residues in NADP(+) recognition. Surprisingly, one of the positively
      charged residues is conserved in all sequences of NAD(+)-dependent enzymes, but
      the conformations adopted by the corresponding regions in proteins whose
      structure has been solved preclude their contribution to the coordination of the
      2'-ribose phosphate of NADP(+). These studies clarify the sequence-structure
      relationships in bacterial GDHs, revealing that identical residues may specify
      different coenzyme preferences, depending on the structural context. Primary
      sequence alone is therefore not a reliable guide for predicting coenzyme
      specificity. We also consider how it is possible for a single sequence to
      accommodate both coenzymes in the dual-specificity GDHs of animals.

PMID- 23879527
TI  - Utility of transcranial sonography in the diagnosis of drug-induced parkinsonism:
      a prospective study.
AB  - BACKGROUND AND PURPOSE: Drug-induced parkinsonism usually resolves after
      discontinuation of the causative agent. However, it persists in some patients,
      who actually have subclinical neurodegenerative parkinsonism. Identification of
      this condition is important because these patients could benefit from therapeutic
      measures. The objective of this study was to prove whether transcranial
      sonography, a technique used in the diagnosis of neurodegenerative parkinsonism,
      can be used for the said identification. METHODS: In this prospective study,
      patients with drug-induced parkinsonism were followed for at least 6 months after
      discontinuation of the causative drug and performance of blinded transcranial
      sonography. Patients were categorized as having iatrogenic parkinsonism if the
      clinical presentation had resolved or subclinical drug-exacerbated parkinsonism
      if it persisted. Once the patient was classified into one of the two groups, an
      expert assessed the transcranial sonography findings and their agreement with the
      clinical diagnosis. RESULTS: Twenty patients composed the group for analysis of
      results. Assessing hyperechogenicity in the substantia nigra >20 mm2 and/or
      hyperechogenic lentiform nucleus, differences were detected between the
      iatrogenic parkinsonism and the subclinical drug-exacerbated parkinsonism groups,
      although they did not reach statistical significance (Fisher's exact test 0.09).
      Joint assessment of sonographic alterations in both structures had a negative
      predictive value of 85.7% for diagnosis of drug-induced parkinsonism, with a
      negative likelihood ratio of 0.3. CONCLUSIONS: Although in our study
      statistically significant differences were not found between the transcranial
      sonography characteristics of subclinical drug-exacerbated parkinsonism and
      iatrogenic parkinsonism patients, we believe that transcranial sonography is a
      valid technique for diagnosis of drug-induced parkinsonism.

PMID- 23879528
TI  - Co-catalyzed radical cycloaddition of [60]fullerene with active dibromides:
      selective synthesis of carbocycle-fused fullerene monoadducts.
AB  - An efficient and highly selective Co-catalyzed radical cycloaddition of
      [60]fullerene with active dibromides for the synthesis of three-, five-, six-,
      and seven-membered carbocycle-fused fullerene monoadducts has been reported. The
      controlled experiments unambiguously disclosed that the reaction proceeds through
      the formation of a fullerene monoradical as a key intermediate. 

PMID- 23879529
TI  - Current recommendations for the diagnosis and treatment of concussion in sport: a
      comparison of three new guidelines.
AB  - Currently, there is considerable debate within the sports medicine community
      about the role of concussion and the risk of chronic neurological sequelae. This
      concern has led to significant confusion among primary care providers and
      athletic trainers about how to best identify those athletes at risk and how to
      treat those with concussion. During the first quarter of 2013, several new or
      updated clinical practice guidelines and position statements were published on
      the diagnosis, treatment, and management of mild traumatic brain
      injury/concussion in sports. Three of these guidelines were produced by the
      American Medical Society for Sports Medicine, The American Academy of Neurology,
      and the Zurich Consensus working group. The goal of each group was to clearly
      define current best practices for the definition, diagnosis, and acute and post
      acute management of sports-related concussion, including specific recommendations
      for return to play. In this article, we compare the recommendations of each of
      the three groups, and highlight those topics for which there is consensus
      regarding the definition of concussion, diagnosis, and acute care of athletes
      suspected of having a concussion, as well as return-to-play recommendations.

PMID- 23879530
TI  - A state wide validation and utilisation study of the Queensland emergency nursing
      workforce tool.
AB  - AIM: To describe and compare standard practice with a revised, assisted method
      for calculating emergency department nursing workforce requirements (using the
      emergency nursing workforce tool, ENWT) within 27 Queensland public hospital
      emergency departments (ED). BACKGROUND: Despite the presence of several
      methodologies used for staffing calculations, there is a necessity to refine
      measures of emergency department complexity and workload to determine appropriate
      staffing in order to meet patient safety needs and health service key priority
      indicators. METHODS: A descriptive comparative study design was employed. Of the
      27 ED nurse unit managers (NUM) invited, 18 (67%) participated. RESULTS: No
      significant difference was noted in the full time equivalent (FTE) nursing
      requirement when standard vs. new (ENWT) methods were compared. The ENWT was more
      efficient (i.e. timely) and had better predictability than existing methods for
      calculating FTE nursing requirement. CONCLUSION: The methodology underpinning the
      ENWT may be useful to apply or adapt to settings other than the ED (e.g.
      intensive care, operating room) and disciplines within the ED other than nursing
      (e.g. medicine, allied health, porterage) to inform staffing requirements.
      IMPLICATIONS FOR NURSING MANAGEMENT: Findings from this research can be used to
      inform ED managers and health service planners regarding a standardized approach
      to calculating emergency nursing workforce needs.

PMID- 23879532
TI  - Callous-unemotional traits and anxiety in a community sample of 7-year-olds.
AB  - In forensic samples of adults and adolescents, there is evidence to suggest that
      there may be distinct variants of psychopathy marked by the presence/absence of
      significant levels of anxiety. Callous-unemotional (CU) traits can be used to
      characterize children who share behavioural and neurocognitive features with
      adult psychopaths. The aims of this paper are to (a) investigate the genetic and
      environmental influences on CU traits with/without anxiety and (b) explore
      differences in terms of concurrent and early parenting and adjustment. Discrete
      groups were formed on the basis of scores in the top 10% of the sample on CU and
      anxiety scales at age 7. Estimates of group heritability were calculated using a
      Defries-Fulker (DF) extremes regression model. Follow back analyses of early
      parenting and adjustment were conducted using multivariate analyses of
      covariance. There was high group heritability for CU traits with/without anxiety.
      Children with both high CU and anxiety showed greater levels of adjustment
      problems than those with CU only at age 7. The two groups did not differ in
      parenting characteristics. In this general population sample, evidence did not
      support differences in etiology for the two groups high on CU traits differing in
      level of anxiety. 

PMID- 23879531
TI  - Use of a hyaluronic acid-carboxymethylcellulose adhesion barrier on the
      neurovascular bundle and prostatic bed to facilitate earlier recovery of erectile
      function after robot-assisted prostatectomy: an initial experience.
AB  - PURPOSE: To investigate the efficacy of hyaluronic acid-carboxymethylcellulose
      (HACM) in facilitating early recovery of erectile function (EF) after radical
      prostatectomy, we report our initial experience of HACM use on the neurovascular
      bundle (NVB) after robot-assisted radical prostatectomy (RARP). PATIENTS AND
      METHODS: Between 2008 and 2010, 459 consecutive patients who underwent RARP with
      bilateral nerve-sparing technique were included in this study. Patients were
      classified into two groups: HACM (group 1; n=162) and non-HACM (group 2; n=287).
      HACM was delivered to the anatomic location of the NVB after prostate removal. We
      retrospectively analyzed the surgical outcomes including EF, continence, and
      perioperative complications. RESULTS: At 6 months after surgery, EF recovery rate
      was 28.5% in group 1 and 17.4% in group 2 (P=0.006). In a subgroup analysis
      consisting of 225 patients with a preoperative International Index of Erectile
      Function Short Survey (IIEF)-5 score >=20, the difference in EF recovery at 6
      months was significant with 62.8% in group 1 and 27.0% in group 2 (P=0.002),
      respectively. HACM use was an independent predictor for EF recovery at 6 months
      after surgery (odds ratio, 2.735; 95% confidence interval, 1.613-4.638; P<0.001).
      Age and preoperative IIEF-5 were also independent predictors. No differences in
      continence at 6 months or perioperative complications were found between the two
      groups. EF recovery was not different between the two groups after 18 months.
      CONCLUSIONS: HACM use around the NVBs is safe and facilitates early recovery of
      EF after nerve-sparing RARP. HACM use is more effective in patients with normal
      preoperative sexual function.

PMID- 23879533
TI  - Overexpression of CDC28 protein kinase regulatory subunit 1B confers an
      independent prognostic factor in nasopharyngeal carcinoma.
AB  - Data mining on public domain identified that CDC28 protein kinase regulatory
      subunit 1B (CKS1B) transcript was highly expressed in nasopharyngeal carcinoma
      (NPC). The expression of CKS1B protein and its clinicopathological associations
      in patients with NPC were further evaluated. Immunoexpression of CKS1B was
      retrospectively assessed in biopsies of 124 consecutive NPC patients without
      initial distant metastasis and treated with consistent guidelines. The
      correlations between CKS1B immunoexpression levels and clinicopathological
      features, as well as patient survivals, were analyzed. High CKS1B expression
      (49.2%) was correlated with the 7th American Joint Committee on Cancer (AJCC)
      stage (p = 0.014). In multivariate analyses, high CKS1B expression emerged as an
      independent prognostic factor for worse disease-specific survival (p < 0.001),
      metastasis-free survival (p < 0.001), and local recurrence-free survival (p =
      0.001). High expression of CKS1B is common and associated with adverse prognostic
      factors and might confer tumor aggressiveness through dysregulation of the cyclin
      dependent protein kinase (intrinsic regulatory activity) during cell cycle
      progression.

PMID- 23879534
TI  - Surface immobilization of engineered nanomaterials for in situ study of their
      environmental transformations and fate.
AB  - The transformation and environmental fate of engineered nanomaterials (ENMs) is
      the focus of intense research due to concerns about their potential impacts in
      the environment as a result of their uniquely engineered properties. Many
      approaches are being applied to investigate the complex interactions and
      transformation processes ENMs may undergo in aqueous and terrestrial
      environments. However, major challenges remain due to the difficulties in
      detecting, separating, and analyzing ENMs from environmental matrices. In this
      work, a novel technique capable of in situ study of ENMs is presented. By
      exploiting the functional interactions between surface modified silver
      nanoparticles (AgNPs) and plasma-deposited polymer films, AgNPs were immobilized
      on to solid supports that can be deployed in the field and retrieved for
      analysis. Either negatively charged citrate or polyethylene glycol, or positively
      charged polyethyleneimine were used to cap the AgNPs, which were deployed in two
      field sites (lake and marina), two standard ecotoxicity media, and in primary
      sewage sludge for a period of up to 48 h. The chemical and physical
      transformations of AgNPs after exposure to different environments were analyzed
      by a combination of XAS and SEM/EDX, taken directly from the substrates. Cystine-
      or glutathione-bound Ag were found to be the dominant forms of Ag in transformed
      ENMs, but different extents of transformation were observed across different
      exposure conditions and surface charges. These results successfully demonstrate
      the feasibility of using immobilized ENMs to examine their likely transformations
      in situ in real environments and provide further insight into the short-term fate
      of AgNPs in the environment. Both the advantages and the limitations of this
      approach are discussed. 

PMID- 23879535
TI  - Number and function impairment of resident C-Kit+ cardiac stem cells in mice with
      renal dysfunction caused by 5/6 nephrectomy.
AB  - BACKGROUND: Cardiac stem cell (CSC) dysfunction exists in various kinds of
      cardiovascular diseases, and may be responsible for the insufficient regeneration
      of cardiac myocytes and coronary vessels. However, whether chronic renal failure
      (CRF) affected CSC is unknown. METHOD: CRF was induced in adult male mice by 5/6
      nephrectomy. The mice were killed at 12 weeks after operation. C-kit+ CSC numbers
      was evaluated by flow cytometer. Apoptosis and DNA damage of C-kit+ CSC in the
      control and CRF mice was analyzed by immunohistochemistry. In the in vitro study,
      normal medium, and medium with uremic rat serum were used for the CSC culture.
      RESULTS: CSC counts attenuated significantly in the chronic renal failure model,
      whereas apoptosis cells and 8-OHdG-positive cells significantly increased. CSC
      derived form 5/6 nephrectomy mice showed an impaired anti-oxidant potential. In
      the cultured cells, CSCs subjected to uremic rat serum showed a higher frequency
      of TUNEL stain-positive and 8-OHdG-positive cells. The uremia rat serum reduced
      the expression of hepatocyte growth factor (HGF) and vascular endothelial growth
      factor (VEGF) in CSC. CONCLUSIONS: The current study elucidated that CSC number
      and function disorders existed in mice with chronic renal insufficiency.
      Apoptosis, oxidative stress and reduced angiogenic factors secretion caused by
      uremic toxins in serum are contributors to CSC dysfunction.

PMID- 23879536
TI  - Conductive thin films of pristine graphene by solvent interface trapping.
AB  - Graphite's insolubility in conventional solvents is a major obstacle to its
      utilization. This challenge is typically addressed by chemical modification such
      as oxidation, followed by reduction. However, pristine graphene possesses
      superior properties as oxidation and reduction lead to degradation of the
      graphene. Here we demonstrate the use of an interfacial trapping technique to
      assemble laterally macroscopic films of pristine graphene that are up to 95%
      transparent. This is accomplished by modest sonication of natural flake graphite
      in a water/heptane mixture to form continuous films at the interface between two
      immiscible liquids. Furthermore, the graphene sheets readily climb hydrophilic
      solid substrates, forming a homogeneous thin film one to four layers thick. These
      films are composed of a network of overlapping graphene sheets and shown to have
      long-range structure with conductivities on the order of 400 S/cm. 

PMID- 23879538
TI  - Intriguing arms race between phages and hosts and implications for better anti
      infectives.
AB  - Phages are viruses of bacteria. The interaction between phages and bacteria shall
      boost both parties' evolution. During the lengthy coevolution, the host has
      evolved multiple mechanisms against the phages. The phages also have evolved
      unique strategies to facilitate their own survival accordingly. This article
      summarizes the measures and countermeasures employed by the both parties and
      their implications for better biomedicines. 

PMID- 23879537
TI  - Vitamin D and microRNAs in bone.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs that orchestrate complex
      posttranscriptional regulatory networks essential to the regulation of gene
      expression. Through complementarity with messenger RNA (mRNA) sequences, miRNAs
      act primarily to silence gene expression through either degradation or inhibited
      translation of target transcripts. In this way, miRNAs can act to fine-tune the
      transcriptional regulation of gene expression, but they may also play distinct
      roles in the proliferation, differentiation, and function of specific cell types.
      miRNA regulatory networks may be particularly important for signaling molecules
      such as vitamin D that exert pleiotropic effects on tissues throughout the body.
      The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D) functions as a
      steroid hormone that, when bound to its nuclear vitamin D receptor, is able to
      regulate target gene expression. However, recent studies have also implicated
      1,25(OH)2D in epigenetic regulation of genes most notably as a modulator of miRNA
      function. The current review details our understanding of vitamin D and miRNAs
      with specific emphasis on the implications of this interaction for biological
      responses to vitamin D in one of its classical target tissues, i.e., bone. 

PMID- 23879539
TI  - Proteomic insights into Acinetobacter baumannii drug resistance and pathogenesis.
AB  - Acinetobacter baumannii is an important opportunist pathogen, due to severe
      antibiotic resistance and nosocomial infection. The epidemiology and antibiotic
      resistance of A.baumannii have been extensively reviewed, but the pathogenesis
      and virulence remain unclear. Proteomics analysis has been applied to study the
      mechanism of drug resistance, biofilm, micronutrient acquisition, and the
      extracellular compartment. This review summarizes applications of proteomics in
      A. baumannii, aiming to summarize novel insights into the mechanism of A.
      baumannii pathogenesis and drug resistance. 

PMID- 23879540
TI  - Pleiotropic roles of TGFbeta/Smad signaling in the progression of chronic liver
      disease.
AB  - A wide range of pathophysiological changes are involved in the progression of
      chronic liver disease (CLD). The multifunctional cytokine transforming growth
      factor beta (TGFbeta) can cross talk with other signaling pathways and mediate
      nearly every aspect of cell physiology from growth to differentiation and cell
      death. TGFbeta can maintain immune response homeostasis and mediate wound-healing
      responses. Additionally, not only can TGFbeta prevent the occurrence of
      hepatocarcinoma by regulating the proliferation of hepatic progenitor cells,
      TGFbeta can also play important roles in blunting inflammation by interfering
      with tumor inhibition response generated by inflammatory mediators. The
      TGFbeta/Smad signaling pathway is an important response that is mediated by
      TGFbeta. This pathway also plays multiple functions in the progression of chronic
      liver disease. The pleiotropic effects of TGFbeta and TGFbeta/Smad signaling
      create challenges in the treatment of CLD under conditions that might interfere
      with the TGFbeta signaling pathway. Detailed understanding of the pleiotropic
      roles of TGFbeta signaling in CLD might assist in the selection of more accurate
      therapeutic approaches, and in the targeting of the right type of cell in the
      development of treatment strategies, and ultimately in achieving the desired
      therapeutic effects. 

PMID- 23879541
TI  - Association between TLR4 polymorphism and periodontitis susceptibility: a meta
      analysis.
AB  - TLR4 has been implicated in periodontal disease, but the association between the
      TLR4 Asp299Gly and Thr399Ile polymorphisms and the risk of periodontal disease
      remains unclear. Therefore, the aim of this study was to investigate the
      association between the TLR4 Asp299Gly and Thr399Ile polymorphism and periodontal
      disease. A search of electronic databases identified previous studies evaluating
      the association of the polymorphisms of TLR4 and periodontitis risk. The
      association was evaluated by odds ratio (OR) and its 95% confidence interval
      (CI). The results showed that TLR4 Asp299Gly and Thr399Ile were not associated
      with a significant risk of periodontitis (OR = 0.96, 95% CI = 0.80-1.16 for G
      versus A; OR = 1.39, 95% CI = 0.82-2.36 for AG/GG versus AA; OR = 1.05, 95% CI =
      0.52-2.15 for T versus C; OR = 0.76, 95% CI = 0.55-1.04 for CT/TT versus CC). In
      the stratified analyses, there was no significantly increased risk for the
      studies of chronic periodontitis and aggressive periodontitis. Our meta-analysis
      revealed that the two common TLR4 polymorphisms, Asp299Gly and Thr399Ile, have no
      association with the likelihood of periodontitis. In a subgroup analysis by
      ethnicity and periodontitis type, the results also did not show any association.
      However, there was a significant increased risk for periodontitis in recessive
      models of Asp299Gly. The effect of genetic networks and their mutual interactions
      in the TLR4 signaling pathway on periodontitis susceptibility needs further
      study. 

PMID- 23879542
TI  - Contributions of the histone arginine methyltransferase PRMT6 to the epigenetic
      function of RUNX1.
AB  - Hematopoietic differentiation is directed by transcription factors such as RUNX1.
      RUNX1 binds to specific DNA binding sites in regulatory elements of genes and
      recruits epigenetic cofactors to target loci. In this way histone modification
      patterns and the chromatin environment are altered, which results in adjusted
      gene expression. The process of transcription factor binding and cofactor
      recruitment is dynamic and strongly influenced by specific posttranslational
      modifications, which are triggered by signaling. In this way cellular signaling
      is integrated at the epigenetic level by transcription factors. The
      identification of epigenetic cofactors and the study of their epigenetic
      influence on transcription is crucial for the understanding of transcription
      factor function in differentiation and disease. In this article, the recent
      observation that RUNX1 is associated with the protein arginine methyltransferase
      6 will be reviewed. PRMT6 triggers H3R2me2a at RUNX1 target genes; this histone
      modification negatively influences the positive H3K4me3 mark and this way acts
      repressive. The RUNX1/PRMT6 association has an impact on bivalent histone marks.
      Upon differentiation, a RUNX1 corepressor complex with PRMT6 is exchanged with a
      RUNX1 coactivator complex. Furthermore, the potential cross talk of transcription
      factors and epigenetic cofactors with histone marks will be discussed. 

PMID- 23879544
TI  - Kinematic and kinetic differences in the execution of vertical jumps between
      people with good and poor ankle joint dorsiflexion.
AB  - The aim of the present study was to investigate the kinematic and kinetic
      differences in the execution of vertical jumps between individuals with good and
      poor ankle dorsiflexion. Fifteen physical education students were assigned to the
      flexible group (FG), while another 15 were assigned to the inflexible group
      (IFG). The two groups executed countermovement jumps (CMJ) and drop jumps from a
      60 cm height (DJ60). For the CMJ, the FG jumped higher (32.0 +/- 4.0 cm vs. 30.2
      +/- 4.9 cm, P = 0.27) and used a greater range of motion in all leg joints. The
      IFG jumpers raised their heels off the ground and had a greater horizontal
      distance between the centre of mass of the trunk and the centre of the hip joint
      (LCMh 25.6 +/- 3.4 cm vs. 30.9 +/- 4.3 cm, P < 0.001). In the DJ60 the FG jumped
      higher (22.4 +/- 5.9 cm vs. 19.5 +/- 4.6 cm, P = 0.14) with a greater vertical
      shift of the body centre of mass (BCM) (S = 0.45 +/- 0.11 cm vs. 0.36 +/- 0.05
      cm, P < 0.01) and better joint coordination. The IFG jumpers changed the position
      of their trunk and heels depending on the jump type. Trainers should reconsider
      the technical issues of vertical jumps according to the flexibility of the ankle
      joint.

PMID- 23879543
TI  - Knockdown of ECHS1 protein expression inhibits hepatocellular carcinoma cell
      proliferation via suppression of Akt activity.
AB  - Overexpression of ECHS1 occurs in different cancers, including hepatocellular
      carcinoma (HCC). ECHS1 is also reported to have an oncogenic activity in various
      human cancers. This study investigated the effect of ECHS1 knockdown on the
      regulation of HCC growth. ECHS1 shRNA suppressed the expression of ECHS1 protein
      in HepG2 cells compared to the negative control vector-transfected HCC cells.
      ECHS1 knockdown also reduced HCC cell viability and enhanced cisplatin-induced
      apoptosis in HCC cells. Akt activation and the expression of various cell cycle
      related genes were inhibited following ECHS1 knockdown. ECHS1 shRNA suppressed
      hepatocellular carcinoma growth in tumor xenograft mice. These data demonstrate
      that ECHS1 may play a role in HCC progression, suggesting that inhibition of
      ECHS1 expression using ECHS1 shRNA should be further evaluated as a novel target
      for the control of HCC. 

PMID- 23879545
TI  - Hip fracture risk factors and the discriminability of hip fracture risk vary by
      age: a case-control study.
AB  - AIMS: To determine the important risk factors for hip fracture and the
      discriminability of hip fracture risk in different age cohorts (<=80 years, >80
      years). METHODS: Consecutive admissions of hip fracture over 24 months in those
      aged >60 years, and an age- and sex-matched control derived from admissions under
      a medical unit were prospectively assessed. The risk factors and the
      discriminabilty of hip fracture risk by age were investigated for each sex in
      univariate and multivariate models. The area under the curve (AUC) statistics
      from the receiver operating characteristic curve analysis was used to estimate
      the ability of the independent risk factors to discriminate hip fracture risk.
      RESULTS: The important risk factors in women aged <=80 years were lower
      bodyweight, previous osteoporotic fracture, hip fracture in first-degree
      relatives and lower plasma 25OHD, and their discriminative effect was (AUC) 0.69.
      Previous osteoporotic fracture and lower plasma 25OHD were the important risk
      factors in men aged <=80 years, with a discriminative effect of 0.83. In the >80
      year age cohorts, only falls was independently associated with hip fracture in
      both sexes, with discriminative effects of 0.60 and 0.62 in females and males,
      respectively. CONCLUSIONS: The overall discrimination of hip fracture risk
      appears less adequate in those aged >80 years when compared with those aged <=80
      years. Although skeletal factors have a greater risk association with hip
      fracture in patients aged <=80 years, it is falls that is important in those aged
      >80 years. The relative importance of risk factors also appears to vary between
      the sexes in those aged <=80 years.

PMID- 23879546
TI  - The role of cardiorenal biomarkers for risk stratification in the early follow-up
      after hospitalisation for acute heart failure.
AB  - CONTEXT: Cardiorenal biomarkers (CBs) predict outcome in acute heart failure
      (AHF). OBJECTIVE: To evaluate CBs in early follow-up prognostication. METHODS: In
      124 AHF patients, levels of CystatinC, NT-proBNP and TroponinI measured five
      weeks from admission (W5) and relative change from day 2 (D2) were assessed for 6
      month prognosis (mortality/HF hospitalization). RESULTS: The combined end-point
      occurred in 33 patients (27%). D2-, W5-cystatin>= median, and lack of
      >=30%decrease in NT-proBNP were independent predictors of outcome. Additionally,
      a risk score established from W5 CBs identified patients with very high event
      rate. CONCLUSIONS: CBs at early follow-up of AHF may guide risk stratification.

PMID- 23879547
TI  - Structural and functional insights into the anti-BACE1 Fab fragment that
      recognizes the BACE1 exosite.
AB  - A molecular modeling study giving structural, functional, and mutagenesis
      insights into the anti-BACE1 Fab fragment that recognizes the BACE1 exosite is
      reported. Our results allow extending experimental data resulting from X-ray
      diffraction experiments in order to examine unknown aspects for the Fab-BACE1
      recognition and its binding mode. Thus, the study performed here allows extending
      the inherently static nature of crystallographic structures in order to gain a
      deeper understanding of the structural and dynamical basis at the atomic level.
      The characteristics and strength of the interatomic interactions involved in the
      immune complex formation are exhaustively analyzed. The results might explain how
      the anti-BACE1 Fab fragment and other BACE1 exosite binders are capable to
      produce an allosteric modulation of the BACE1 activity. Our site-directed
      mutagenesis study indicated that the functional anti-BACE1 paratope, residues
      Tyr32 (H1), Trp50 (H2), Arg98 (H3), Phe101 (H3), Trp104 (H3) and Tyr94 (L3),
      strongly dominates the binding energetics with the BACE1 exosite. The mutational
      studies described in this work might accelerate the development of new BACE1
      exosite binders with interesting pharmacological activity. 

PMID- 23879548
TI  - Prognosis of Deantigenated Equine Bone Used for Bone Augmentation: A Multicenter
      Retrospective Study on Early and Late Postsurgical Complications in 81
      Consecutive Patients.
AB  - PURPOSE: To evaluate the clinical outcome of deantigenated equine bone (DEB)
      grafts in a series of patients treated with DEB at six months postaugmentation.
      MATERIALS AND METHODS: One hundred DEB grafts were inserted in 81 patients
      between January 2004 and December 2006. Thirty-two DEBs were blocks and 68 were
      granules (52 sinus lift and 16 guided bone regeneration [GBR] procedures
      performed). A total of 147 implants were inserted. A Pearson chi-square test was
      used to detect any statistically significant correlation between the studied
      variables and early and/or late failures. RESULTS: There were 6 early and 26 late
      graft failures and another 16 failures after prosthesis placement. The overall
      failure rate was 25% in the GBR procedures, 31.9% in sinus lift, and 54.3% with
      blocks, for a total complication rate of 39.5%. A statistically significant
      relation was detected with respect to graft type and early complications (p =
      .005), with a worse outcome for DEB blocks compared to granules. After
      provisional prosthesis restoration, 23 implants were lost, and another 41 failed
      after definitive prosthesis delivery, for an overall failure rate of 43.5%. The
      follow-up period was 3 years after surgery. CONCLUSIONS: DEB grafting material
      had a very high rate of complications. Blocks had more than 50% failures, mainly
      in the immediate postoperative period. Other procedures such as GBR and sinus
      lift also showed more than 25% infections and resorption, and late failures
      (i.e., after-implant placement) were also common. Our results show that DEB is
      less than ideal for crestal bone reconstruction.

PMID- 23879549
TI  - Bullous eosinophilic cellulitis associated with giardiasis.

PMID- 23879552
TI  - Recognizing the role of surgical oncology and cancer imaging in the
      multidisciplinary approach to cancer: an important area of future scholarly
      growth for BMC Cancer.

PMID- 23879551
TI  - Elevated peripheral leukocyte counts in acute cervical artery dissection.
AB  - BACKGROUND AND PURPOSE: It has been suggested that inflammation may play a role
      in the development of cervical artery dissection (CeAD), but evidence remains
      scarce. METHODS: A total of 172 patients were included with acute (< 24 h) CeAD
      and 348 patients with acute ischaemic stroke (IS) of other (non-CeAD) causes from
      the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study, and
      223 age- and sex-matched healthy control subjects. White blood cell (WBC) counts
      collected at admission were compared across the three groups. RESULTS: Compared
      with healthy control subjects, CeAD patients and non-CeAD stroke patients had
      higher WBC counts (P < 0.001). Patients with CeAD had higher WBC counts and were
      more likely to have WBC > 10 000/MUl than non-CeAD stroke patients (38.4% vs.
      23.0%, P < 0.001) and healthy controls (38.4% vs. 8.5%, P < 0.001). WBC counts
      were higher in CeAD (9.4 +/- 3.3) than in IS of other causes (large artery
      atherosclerosis, 8.7 +/- 2.3; cardioembolism, 8.2 +/- 2.8; small vessel disease,
      8.4 +/- 2.4; undetermined cause, 8.8 +/- 3.1; P = 0.022). After adjustment for
      age, sex, stroke severity and vascular risk factors in a multiple regression
      model, elevated WBC count remained associated with CeAD, as compared with non
      CeAD stroke patients [odds ratio (OR) = 2.56; 95% CI 1.60-4.11; P < 0.001) and
      healthy controls (OR = 6.27; 95% CI 3.39-11.61; P < 0.001). CONCLUSIONS: Acute
      CeAD was associated with particularly high WBC counts. Leukocytosis may reflect a
      pre-existing inflammatory state, supporting the link between inflammation and
      CeAD.

PMID- 23879553
TI  - Necropsy findings in dogs that died during grooming or other pet service
      procedures.
AB  - Procedures involved in grooming, bathing, and other pet services can often lead
      animals to death. Of the necropsies of 1391 animals carried out at a private
      diagnostic laboratory in Sao Paulo, Brazil from 2004 to 2009, 94 were dogs that
      died during the above-mentioned procedures. Young male dogs and small breeds like
      Poodle Miniature, Yorkshire Terrier, and Lhasa Apso were most frequently
      observed. Blunt-force trauma was responsible for the deaths of 31% of the
      animals, with a higher incidence of trauma to the head, characterized chiefly by
      fractures and nervous tissue lesions. In the other 69% of cases, the animals
      showed signs of stress, and died due to pulmonary edema and hemorrhage. As we
      cannot rule out the intentional character in some situations, this article
      provides veterinary forensic support for veterinarians and pet owners, especially
      in lawsuits, helping in finding the cause of animal's death in such pet services.

PMID- 23879554
TI  - Competing hydrogen-bonding, decomposition, and reversible dimerization mechanisms
      during the one- and two-electron electrochemical reduction of retinal (vitamin
      A).
AB  - Retinal (R) can be sequentially voltammetrically reduced in CH3CN in two one
      electron processes to form first the anion radical (R(*-)) at -1.75 (+/-0.04) V
      vs Fc/Fc(+) (Fc = ferrocene) then the dianion (R(2-)) at -2.15 (+/-0.04) V vs
      Fc/Fc(+). The anion radical undergoes a reversible dimerization reaction to form
      the dianion (R2(2-)) with a forward dimerization rate constant k(dim) = 8 * 10(2)
      L mol(-1) s(-1) and a reverse monomerization rate constant k(mon) = 2 * 10(-2) s(
      1) at 295 K. All three anion species (anion radical, dianion, and dimer dianion)
      undergo hydrogen-bonding interactions with water that is present at millimolar
      levels in the solvent. As the water content of the solvent increases, the fate of
      the reduced compounds is determined by chemically irreversible hydrolysis
      reactions with H2O and decomposition reactions of the highly charged R(2-). Bulk
      controlled potential electrolysis experiments combined with NMR analysis of the
      reaction solutions indicate that the reduction occurs at the aldehyde group of
      retinal. The electrochemical data obtained under a range of experimental
      conditions (varying voltammetric scan rates, temperatures, H2O content of
      solutions, and retinal concentrations) were modeled by digital simulation
      techniques to determine the kinetic and thermodynamic parameters associated with
      all of the homogeneous reactions.

PMID- 23879550
TI  - Cortical spreading depression as a target for anti-migraine agents.
AB  - Spreading depression (SD) is a slowly propagating wave of neuronal and glial
      depolarization lasting a few minutes, that can develop within the cerebral cortex
      or other brain areas after electrical, mechanical or chemical depolarizing
      stimulations. Cortical SD (CSD) is considered the neurophysiological correlate of
      migraine aura. It is characterized by massive increases in both extracellular K+
      and glutamate, as well as rises in intracellular Na+ and Ca2+. These ionic shifts
      produce slow direct current (DC) potential shifts that can be recorded
      extracellularly. Moreover, CSD is associated with changes in cortical parenchymal
      blood flow. CSD has been shown to be a common therapeutic target for currently
      prescribed migraine prophylactic drugs. Yet, no effects have been observed for
      the antiepileptic drugs carbamazepine and oxcarbazepine, consistent with their
      lack of efficacy on migraine. Some molecules of interest for migraine have been
      tested for their effect on CSD. Specifically, blocking CSD may play an enabling
      role for novel benzopyran derivative tonabersat in preventing migraine with aura.
      Additionally, calcitonin gene-related peptide (CGRP) antagonists have been
      recently reported to inhibit CSD, suggesting the contribution of CGRP receptor
      activation to the initiation and maintenance of CSD not only at the classic
      vascular sites, but also at a central neuronal level. Understanding what may be
      lying behind this contribution, would add further insights into the mechanisms of
      actions for "gepants", which may be pivotal for the effectiveness of these drugs
      as anti-migraine agents. CSD models are useful tools for testing current and
      novel prophylactic drugs, providing knowledge on mechanisms of action relevant
      for migraine.

PMID- 23879555
TI  - Pseudoainhum in a patient with tuberous sclerosis complex: a case report and
      review of the literature.

PMID- 23879556
TI  - Association of Helicobacter pylori infection with diabetic complications: a meta
      analysis.
AB  - BACKGROUND. Helicobacter pylori (HP) infects more than half of the world's
      population. The aim of the study was to quantify the association between HP and
      the risk of diabetic complications. METHODS: A literature search was performed to
      identify studies published between 1998 and 2012 for relevant risk estimates.
      Fixed and random effect meta-analytical techniques were conducted for ischemic
      heart disease, retinopathy, neuropathy and nephropathy. RESULTS: Eight studies
      were included. HP was associated with an increase risk of nephropathy and
      neuropathy (relative risk [RR]: 1.35, 95% CI: 1.06-1.73, p = 0.45 and RR: 1.20,
      95% CI: 1.03-1.40, p = 0.29). We also discovered significant associations between
      bacterial infection and nephropathy risk in Oriental people (RR: 1.73, 95% CI:
      1.19-2.50, p = 0.82) and in type 2 diabetic patients (RR: 1.50, 95% CI: 1.11
      2.02, p = 0.29). CONCLUSIONS: Our meta-analyses suggest a possible relationship
      between HP and the risk of nephropathy and neuropathy. Our results also suggest
      that the effect of HP on the risk of nephropathy is stronger in Oriental people
      and in type 2 DM patients.

PMID- 23879557
TI  - Enhancing the performance of polymer photovoltaic cells by using an alcohol
      soluble fullerene derivative as the interfacial layer.
AB  - Alcohol soluble fullerene derivative (FN-C60) has been synthesized and used as a
      cathode interfacial layer for high-efficiency polymer solar cells (PSCs). To
      examine the function of the FN-C60 interfacial layer, polymer solar cells were
      fabricated with blends of P3:PC71BM, HXS-1:PC71BM, PDFCDTBT:PC71BM, and
      PDPQTBT:PC71BM as the active layer. In comparison to the bare Al electrode, power
      conversion efficiencies (PCEs) of P3:PC71BM, HXS-1:PC71BM, PDFCDTBT:PC71BM, and
      PDPQTBT:PC71BM based PSCs were increased from 3.50 to 4.64%, 4.69 to 5.25%, 2.70
      to 4.60%, and 1.52 to 2.29%, respectively, when FN-C60/Al was used as the
      electrode. Moreover, the overall photovoltaic performances of PSCs with the FN
      C60/Al electrode were better than those of cells with LiF/Al electrode,
      indicating that FN-C60 is a potential interfacial layer material to replace LiF. 

PMID- 23879558
TI  - Person-centred climate questionnaire (PCQ-S): establishing reliability and cut
      off scores in residential aged care.
AB  - AIM: This study aimed to establish reliability and cut-off scores for the person
      centred climate questionnaire - staff version (PCQ-S) in residential aged care.
      BACKGROUND: A number of tools have emerged recently to measure person
      centredness, and these need psychometric evaluation and cut-off scores to enhance
      utilisation and interpretation. METHOD: A cross-sectional survey design was
      employed in a Swedish sample of residential aged care staff (n = 1237).
      Psychometric evaluation using Cronbach's alpha and item-total correlation was
      used, together with establishing cut-off scores based on quartile scores. RESULT:
      The PCQ-S had satisfactory psychometric properties and the following total scale
      cut-off scores for unit person-centredness were suggested: <= 49 ('well below
      average'), 50-56 ('below average'), 57-62 ('above average') and >= 63 ('well
      above average'). These cut-off scores were clinically meaningful as they
      separated the sample into four groups in which staff in more person-centred units
      reported significantly higher work satisfaction, social support and less stress
      of conscience. CONCLUSION: The PCQ-S has reliability in residential aged care
      samples, and cut-off scores are provided that provide important fundaments for
      comparative studies and aggregation of data to explore person-centredness care
      further. IMPLICATIONS FOR NURSING MANAGEMENT: The study enables managers with
      ways to measure, interpret and compare levels of person-centredness between units
      and facilities for research, practice development and/or benchmarking purposes.

PMID- 23879559
TI  - An introduction to primary skin imaging.
AB  - Dermatology is a field in which clinical examination is heavily relied upon for
      diagnosis. When required, a tissue biopsy may also be performed to confirm the
      diagnosis. Recent advances in imaging techniques have been applied to cutaneous
      lesions to improve diagnostic accuracy without the need for biopsy. These new
      imaging techniques are reviewed for their developing role in dermatology. 

PMID- 23879561
TI  - Functional differentiation of small heat shock proteins in diapause-destined
      Artemia embryos.
AB  - Encysted embryos of Artemia franciscana cease development and enter diapause, a
      state of metabolic suppression and enhanced stress tolerance. The development of
      diapause-destined Artemia embryos is characterized by the coordinated synthesis
      of the small heat shock proteins (sHsps) p26, ArHsp21 and ArHsp22, with the
      latter being stress inducible in adults. The amounts of sHsp mRNA and protein
      varied in Artemia cysts, suggesting transcriptional and translational regulation.
      By contrast to p26, knockdown of ArHsp21 by RNA interference had no effect on
      embryo development. ArHsp21 provided limited protection against stressors such as
      desiccation and freezing but not heat. ArHsp21 may have a non-essential or
      unidentified role in cysts. Injection of Artemia adults with amounts of ArHsp22
      double-stranded RNA less than those used for other sHsps killed females and
      males, curtailing the analysis of ArHsp22 function in developing embryos and
      cysts. The results indicate that diapause-destined Artemia embryos synthesize
      varying amounts of sHsps as a result of differential gene expression and mRNA
      translation and also suggest that these sHsps have distinctive functions.

PMID- 23879560
TI  - Controlled cortical impact results in an extensive loss of dendritic spines that
      is not mediated by injury-induced amyloid-beta accumulation.
AB  - The clinical manifestations that occur after traumatic brain injury (TBI) include
      a wide range of cognitive, emotional, and behavioral deficits. The loss of
      excitatory synapses could potentially explain why such diverse symptoms occur
      after TBI, and a recent preclinical study has demonstrated a loss of dendritic
      spines, the postsynaptic site of the excitatory synapse, after fluid percussion
      injury. The objective of this study was to determine if controlled cortical
      impact (CCI) also resulted in dendritic spine retraction and to probe the
      underlying mechanisms of this spine loss. We used a unilateral CCI and visualized
      neurons and dendtritic spines at 24 h post-injury using Golgi stain. We found
      that TBI caused a 32% reduction of dendritic spines in layer II/III of the
      ipsilateral cortex and a 20% reduction in the dendritic spines of the ipsilateral
      dentate gyrus. Spine loss was not restricted to the ipsilateral hemisphere,
      however, with similar reductions in spine numbers recorded in the contralateral
      cortex (25% reduction) and hippocampus (23% reduction). Amyloid-beta (Abeta), a
      neurotoxic peptide commonly associated with Alzheimer disease, accumulates
      rapidly after TBI and is also known to cause synaptic loss. To determine if Abeta
      contributes to spine loss after brain injury, we administered a gamma-secretase
      inhibitor LY450139 after TBI. We found that while LY450139 administration could
      attenuate the TBI-induced increase in Abeta, it had no effect on dendritic spine
      loss after TBI. We conclude that the acute, global loss of dendritic spines after
      TBI is independent of gamma-secretase activity or TBI-induced Abeta accumulation.

PMID- 23879562
TI  - Molecular characterization of dissolved organic matter through a desalination
      process by high resolution mass spectrometry.
AB  - The effect of different water treatments such as ultrafiltration (UF) and reverse
      osmosis (RO) on dissolved organic matter (DOM) is still unknown. Electrospray
      ionization Fourier transform orbitrap mass spectrometry has been used to provide
      valuable information of marine DOM evolution through a desalination process on a
      molecular scale. In the present manuscript, the characterization of four real
      composite water samples from a desalination pilot plant installed in the coast of
      Barcelona (Spain) has been carried out. The sampling was performed on each point
      of the pilot plant: raw seawater (RSW), UF effluent, brine RO and permeate RO.
      The mass spectra of the different samples show several thousand peaks, however
      for the present screening study, only the mass range m/z 200-500 and the main
      signals in this mass range (relative intensities >=1%) have been considered. The
      analysis of RSW and UF samples reveal that there is little effect on DOM by the
      UF pilot. However, when the water is treated on the RO an important change on DOM
      has been observed. The recurring periodical patterns found in RSW and UF are lost
      in Permeate RO sample. Compounds with more aliphatic character, with higher H/C
      ratio (H/Cav 1.72) are present in the Permeate and some of them have been
      tentatively identified as fatty acids. 

PMID- 23879564
TI  - Distribution of infused umbilical cord mesenchymal stem cells in a rat model of
      renal interstitial fibrosis.
AB  - AIMS: Stem cell transplantation for the treatment of kidney diseases is dependent
      on choice of transplant pathway. We evaluated the safety of human umbilical cord
      mesenchymal stem cells through peripheral infusion and their distribution in a
      rat model of renal interstitial fibrosis (RIF). METHOD: Cryopreserved umbilical
      cord mesenchymal stem cells were infused via tail vein injection into rats with
      unilateral ureteral obstruction and Sham-operated. Blood, kidney, heart, liver,
      spleen and lung were collected at 14, 21, and 28 days after infusion. Testing
      included microscopic observation of kidney morphological changes and
      immunohistochemical testing to identify and count the number of MAB1281 (labeled
      human cells) positive cells in the heart, liver, spleen, lungs, and kidneys of
      different treatment groups. RESULTS: There was no significant difference in the
      Sham-operated group and Sham-operated + cell transplantation group at different
      time points. Human cells were identified mainly in the lungs, spleen, and kidney.
      The number of human umbilical cord mesenchymal stem cells in the kidney was
      greater in the unilateral ureteral obstruction + cell transplantation group,
      compared to the Sham-operated + cell transplantation group. human umbilical cord
      mesenchymal stem cells were mainly located in the interstitium of the left
      kidney. These results suggest that infused mesenchymal stem cells were primed to
      engraft a damaged kidney, especially damaged renal interstitium. CONCLUSIONS:
      Intravenous infusion of exogenous umbilical cord mesenchymal stem cells is
      feasible and safe. Infused mesenchymal stem cells can reach damaged kidney
      tissues with obstructive RIF after a vein graft.

PMID- 23879563
TI  - Prevalence of hepatitis B and hepatitis D coinfection in asymptomatic blood
      donors in Iran.
AB  - Hepatitis delta virus (HDV) is a satellite virus that needs hepatitis B virus
      (HBV) surface antigen for amplification and transition. HDV appears in HBsAg
      carriers as acute coinfection and superinfection in patients with chronic
      hepatitis B. This coinfection leads to chronic hepatitis, cirrhosis, and liver
      carcinoma. The aim of this study was to detect the prevalence of coinfection and
      superinfection of HBVs and HDVs in blood donor individuals in Iran. Sera from 854
      asymptomatic blood donors from the Bank of positive samples storage at the
      National Blood Transfusion Organization of Iran that were positive for hepatitis
      B surface antigen were analysed. The presence of antibody against HDV in blood
      donors was detected using ELISA followed by conventional PCR, seminested PCR and
      real-time PCR to determine coinfection and/or superinfection. Restriction
      fragment length polymorphism was used for HDV genotyping. All 854 samples were
      HBsAg and anti-HBc positive whereas only 18 (2%) of them were positive for anti
      HDV. Of the 854 samples, 154 (18%) were HBV-DNA positive. HDV-RNA was detected in
      0.6% of the total samples by seminested PCR and real-time PCR and the two PCR
      methods produced similar results. Moreover, 16.6% and 83.4% of anti-HDV-positive
      samples exhibited coinfection and superinfection with HBV, respectively. Genotype
      I of HDV was determined in positive samples. 

PMID- 23879565
TI  - Self-assembly of condensable "bola-amphiphiles" in water/tetraethoxysilane
      mixtures for the elaboration of mesostructured hybrid materials.
AB  - The self-assembly of condensable amphiphile molecules in water is an attractive
      approach for the synthesis of mesostructured hybrid materials. In this article,
      we focus on aminoundecyltriethoxysilane (AUT), a condensable "bola-amphiphile",
      i.e., an amphiphilic molecule possessing two polar heads on both sides of an
      aliphatic chain. In the present case, one side is a condensable triethoxysilane,
      and the other side is an amino group. We report on the self-assembly of AUT in
      mixtures of water and tetraethoxysilane (TEOS). In situ small-angle X-ray
      scattering (SAXS) measurements allowed us to follow the evolution of the
      structure from the liquid state up to the solid material formed upon catalytic
      polycondensation. Depending on the medium composition, hexagonal or lamellar
      structures can be observed in the final material. These observations allowed us
      to propose a model for the self-assembly of AUT in water/TEOS mixtures that we
      were able to validate by simulations of the SAXS profiles. By taking advantage of
      the modularity of such a system, it proves possible to prepare in a simple way
      various structured hybrid materials possessing a high number of available organic
      functions without using sacrificial surfactant molecules. 

PMID- 23879566
TI  - Synthesis of 3,3'-spirocyclic oxindoles via phosphine catalyzed [4 + 2]
      cyclizations.
AB  - Triphenylphosphine promoted reactions between 3-arylideneoxindoles and delta-aryl
      substituted penta-2,3-dienoates afford an unprecedented access to spirocyclic
      oxindoles with functionalized six-membered rings. In these new [4 + 2]
      cyclization processes, the allenoates operate as the four-carbon synthons, thanks
      to the involvement of the substituted delta-carbons. These reactions give
      excellent control of the relative stereochemistry of the three stereogenic
      centers. The stereochemistry of the final product has been ascertained by X-ray
      diffraction studies. 

PMID- 23879567
TI  - Filtering of nanoparticles with tunable semiconductor membranes.
AB  - Translocation dynamics of nanoparticles permeating through the nanopore in an n
      Si semiconductor membrane is studied. With the use of Brownian Dynamics to
      describe the motion of the charged nanoparticles in the self-consistent membrane
      electrolyte electrostatic potential, we asses the possibility of using our
      voltage controlled membrane for the macroscopic filtering of the charged
      nanoparticles. The results indicate that the tunable local electric field inside
      the membrane can effectively control interaction of a nanoparticle with the
      nanopore by either blocking its passage or increasing the translocation rate. The
      effect is particularly strong for larger nanoparticles due to their stronger
      interaction with the membrane while in the nanopore. By extracting the membrane
      permeability from our microsopic simulations, we compute the macroscopic sieving
      factors and show that the size selectivity of the membrane can be tuned by the
      applied voltage. 

PMID- 23879568
TI  - Surface coating of graphene quantum dots using mussel-inspired polydopamine for
      biomedical optical imaging.
AB  - Because of the superiority of GQDs (graphene quantum dots) in biomedical imaging,
      in terms of biocompatibility and toxicity of semiconductor quantum dots, GQDs
      bring new opportunities for the diagnosis and detection of diseases. In this
      study, we synthesized photoluminescent (PL) graphene quantum dots (GQDs) through
      a simple exfoliation and oxidation process, and then coated them with
      polydopamine (pDA) for enhanced stability in water and low toxicity in vivo. From
      the results, the GQDs coated with pDA showed an excellent stability of PL
      intensity. It showed that the PL intensity of noncoated GQDs in PBS solution
      rapidly decreased with time, resulting in a 45% reduction of the PL intensity for
      14 days of incubation in PBS solution. After coating with polydopamine, PL
      intensities of polydopamine-coated GQDs was maintained more stably for 14 days
      compared with uncoated GQDs. We have observed the in vitro and in vivo
      biocompatibility of pDA-coated GQDs in nude mice. The overall observation
      revealed that pDA-coated GQDs could be used as a long-term optical imaging agent
      as well as a biocompatible drug carrier. 

PMID- 23879569
TI  - New phases found in reverse micelle systems with high concentrations of AOT.
AB  - This paper discusses the phase behavior, rheology, and structure of self
      assembled sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelle systems
      at high AOT concentrations. When the amount of AOT and w(o) (the molar ratio of
      water to AOT) were changed, many different phases were found, a fact which is not
      discussed in the literature. Opaque gel-like phase (phase separation) occurred
      with high concentrations of AOT in organic solvents without water. When the AOT
      concentration and w(o) were increased to 18-72 m and 2, respectively, the samples
      were gel-like and translucent. Dynamic rheological results indicate that the
      viscoelastic transition agreed with a multirelaxation time model. Small-angle X
      ray scattering (SAXS) results imply that these samples showed a hexagonally close
      packed cylindrical structure in which the diameter of a cylinder was ~2.5-3.0 nm,
      depending on the water contents. Moreover, these AOT cylinders self-assembled
      into fiber bundles with a diameter of 1-10 MUm, as determined using a polarized
      optical microscope. As w(o) was increased to 2-6 in 72 m AOT samples, similar
      rheological and SAXS results were obtained. However, a different type of
      viscoelastic transition occurred, from multirelaxation to single-relaxation, when
      w(o) was increased to 7-11. The samples were in the transparent gel-like phase,
      and the structures determined by SAXS were a combination of hexagonally packed
      cylindrical and lamellar structure. The close-packed cylindrical structures had
      larger radii and shorter lengths with increasing w(o). Furthermore, when w(o) was
      increased to 12, the gel-like phase disappeared and a highly viscous solution was
      observed. This is because all the cylindrical structures collapsed and
      transformed into lamellar structures when the amount of water was further
      increased.

PMID- 23879570
TI  - Effect of stance position on kick performance in taekwondo.
AB  - In taekwondo, the stance position can potentially affect kick performance. The
      aim of this study was to analyse mechanical variables in the roundhouse kick in
      taekwondo according to three stance positions (0 degrees , 45 degrees , 90
      degrees ). Nine experienced taekwondo athletes performed consecutive kicking
      trials in a random order according to these three relative positions of the feet
      on the ground. Measurements for the mechanical analysis were performed using two
      3D force plates and an eight-camera motion capture system. The taekwondo
      athletes' reaction and execution times were shorter when starting from the 0
      degrees  and 45 degrees  stance positions than from the 90 degrees  position (P <
      0.05). Moreover, the ground reaction force was negatively correlated with
      execution time and positively with velocity of thigh and shank. Our results
      suggest that the stance position affects the execution technique of taekwondo
      athletes' kicks. It is suggested that athletes should not adopt the 90 degrees 
      stance position because it will not enable them to achieve the best performance
      in the roundhouse kick.

PMID- 23879571
TI  - A strategy to select suitable physicochemical attributes of amino acids for
      protein fold recognition.
AB  - BACKGROUND: Assigning a protein into one of its folds is a transitional step for
      discovering three dimensional protein structure, which is a challenging task in
      bimolecular (biological) science. The present research focuses on: 1) the
      development of classifiers, and 2) the development of feature extraction
      techniques based on syntactic and/or physicochemical properties. RESULTS: Apart
      from the above two main categories of research, we have shown that the selection
      of physicochemical attributes of the amino acids is an important step in protein
      fold recognition and has not been explored adequately. We have presented a multi
      dimensional successive feature selection (MD-SFS) approach to systematically
      select attributes. The proposed method is applied on protein sequence data and an
      improvement of around 24% in fold recognition has been noted when selecting
      attributes appropriately. CONCLUSION: The MD-SFS has been applied successfully in
      selecting physicochemical attributes of the amino acids. The selected attributes
      show improved protein fold recognition performance.

PMID- 23879572
TI  - Serum brain-derived neurotrophic factor levels in epilepsy.
AB  - BACKGROUND AND PURPOSE: To clarify the utility of serum brain-derived
      neurotrophic factor (BDNF) as a biomarker for epilepsy diagnosis and severity.
      METHODS: Serum BDNF levels in 135 consecutive people with epilepsy meeting our
      criteria were assessed. Controls were 34 healthy individuals who over 12 months
      or longer had no complaints or signs of a neurological disorder. Serum BDNF
      concentrations were measured using Luminex technology. RESULTS: Gender, but not
      age, was found to be a significant factor related to serum BDNF levels in
      controls and people with epilepsy. Serum BDNF levels in people with epilepsy
      (mean 8798.5, SE 321.5 pg/ml) were not different from those of controls (mean
      8919.5, SE 709.0 pg/ml). A multiple linear regression analysis, however, suggests
      that seizure frequency (P < 0.001) and epilepsy duration (P = 0.025) negatively
      correlate with serum BDNF levels independently of other factors. When BDNF cut
      off values of 6260 pg/ml were used, the sensitivity for distinguishing people
      with daily or more frequent seizures from those with fewer seizures was 80% and
      specificity was 90%. CONCLUSIONS: It seems that the concentration of BDNF in
      serum is associated with disease severity in people with epilepsy and may be a
      helpful marker for severity.

PMID- 23879574
TI  - Prognostic impact of LIM domain only 2 (LMO2) in chronic myelogenous leukaemia.

PMID- 23879573
TI  - Cortico-cortical, cortico-striatal, and cortico-thalamic white matter fiber
      tracts generated in the macaque brain via dynamic programming.
AB  - Probabilistic methods have the potential to generate multiple and complex white
      matter fiber tracts in diffusion tensor imaging (DTI). Here, a method based on
      dynamic programming (DP) is introduced to reconstruct fibers pathways whose
      complex anatomical structures cannot be resolved beyond the resolution of
      standard DTI data. DP is based on optimizing a sequentially additive cost
      function derived from a Gaussian diffusion model whose covariance is defined by
      the diffusion tensor. DP is used to determine the optimal path between initial
      and terminal nodes by efficiently searching over all paths, connecting the nodes,
      and choosing the path in which the total probability is maximized. An ex vivo
      high-resolution scan of a macaque hemi-brain is used to demonstrate the
      advantages and limitations of DP. DP can generate fiber bundles between distant
      cortical areas (superior longitudinal fasciculi, arcuate fasciculus, uncinate
      fasciculus, and fronto-occipital fasciculus), neighboring cortical areas (dorsal
      and ventral banks of the principal sulcus), as well as cortical projections to
      the hippocampal formation (cingulum bundle), neostriatum (motor cortical
      projections to the putamen), thalamus (subcortical bundle), and hippocampal
      formation projections to the mammillary bodies via the fornix. Validation is
      established either by comparison with in vivo intracellular transport of
      horseradish peroxidase in another macaque monkey or by comparison with atlases.
      DP is able to generate known pathways, including crossing and kissing tracts.
      Thus, DP has the potential to enhance neuroimaging studies of cortical
      connectivity.

PMID- 23879575
TI  - Evaluating necrosis and chemotherapy response in colorectal cancer liver
      metastases. Comment on Knijn et al. (2013).

PMID- 23879576
TI  - Effects of estradiol on high-voltage-activated Ca(2+) channels in cultured rat
      cortical neurons.
AB  - OBJECTIVES: Estrogen regulates a wide variety of nonreproductive functions in the
      central nervous system. Cortical neurons contain a diverse range of voltage-gated
      ion channels, including calcium (Ca(2+)) channels, and Ca(2+) channels play an
      important role in the regulation of action potential generation and neuronal
      excitability. In this study, the effect of estradiol (E2) on high-voltage
      activated (HVA) Ca(2+) channels in cultured rat cortical neurons was examined.
      METHODS: We used the whole-cell patch-clamp technique to measure the HVA Ca(2+)
      channels. RESULTS: We found that HVA Ca(2+) channel currents was inhibited by
      17beta-E2 in a rapid, reversible and concentration-dependent manner. Moreover,
      17beta-E2 shifted the steady-state inactivation curve in the hyperpolarizing
      direction without changing the activation curve. We also found that the
      inhibitory effects of 17beta-E2 on Ca(2+) currents were unaffected by the
      estrogen receptor (ER) antagonist ICI 182780; however, the protein kinase C (PKC)
      inhibitor rottlerin and protein kinase A (PKA) inhibitor H-89 blocked the 17beta
      E2-induced inhibition of Ca(2+) currents. CONCLUSIONS: E2 inhibited HVA Ca(2+)
      currents via PKC and PKA-dependent signaling pathway in cortical neurons, and the
      effects of BPA were independent of classical ER.

PMID- 23879577
TI  - Rehabilitation of edentulous mandibles by means of osseointegrated implants: a 5
      year follow-up study on one or two-stage surgery, number of implants, implant
      surfaces, and age at surgery.
AB  - BACKGROUND: In three former reports, the present team has presented the 1-year
      outcome of four different treatment procedures handling the edentulous mandible;
      that is, two-stage and one-stage surgery with turned Branemark System(r) (Nobel
      Biocare AB, Gothenburg, Sweden) implants (Group 1 and 2) and one-stage surgery
      using either 5 or 4 TiUniteTM (Nobel Biocare AB, Gothenburg, Sweden) implants
      (Group 3 and 4). PURPOSE: The aim of the present investigation was to follow up
      these patients for a period of 5 years with regard to implant/prosthesis
      cumulative survival rates, marginal bone loss calculations, clinical
      complications, and results related to age at surgery. MATERIALS AND METHODS: A
      total of 385 patients, provided with 1,838 implants, were originally included in
      the four patient groups. All patients received fixed prostheses. The overall
      majority of patients had each five implants placed. Radiographs were obtained at
      prosthesis delivery, at the 1 and 5-year follow-up. RESULTS: A total of 1,230
      implants in 259 patients (67%) were possible to follow up for 5 years. Implant
      Cumulative Survival Rates (CSR) in 5 years for Groups 1-4 were 99.7, 97.0, 98.5,
      and 98.6%. The corresponding prosthesis treatment CSR was 100, 99.3, 98.5, and
      98.6%, respectively. Significantly, more patients (p< .05) lost turned implants
      after one-stage surgery (Group 2). Frequency distributions of implants revealed
      that >1.2 mm bone loss was observed around 75 implants (6.4%). The moderately
      rough central (midline) implant showed more bone loss than other placed implants
      (Group 3; p< .05). The youngest half of included patients at surgery
      (Youngest(50%) ; n=193) presented significantly higher mortality than older
      patients as well as compared to normal population (p< .05). Patients in the
      Younger(50%) group showed also an association to patients with complete loss of
      all implants and patients with most implants with obvious bone loss after 5
      years. CONCLUSIONS: All four treatment procedures served well during the 5 years
      of follow-up and only eight patients (2.1%) were complete failures or showed
      obvious bone loss (>1.8 mm) at several implants (>2 implants), mostly observed in
      younger patients. The few complications in relation to implant failure and/or
      obvious bone loss could be associated to both local impact factors (surface,
      implant site, surgical protocol) as well as to host response factors (systemic
      health).

PMID- 23879578
TI  - Health behavior and adherence to treatment for sleep breathing disorder in the
      patient with heart failure.
AB  - BACKGROUND: Heart failure can be complicated by a variety of comorbidities
      including sleep breathing disorder (SBD). Treatment for SBD in the heart failure
      patient can improve quality of life and decrease mortality. Few studies have
      sought to examine the reasons why patients with heart failure who screen positive
      for SBD do not follow through with diagnostic testing and recommendations for
      evidence based treatments. PURPOSE: The purpose of this study was to describe and
      compare the characteristics of patients with heart failure who adhered to
      recommendations for evaluation and treatment of SBD with those who did not.
      Additionally, the study sought to examine reasons for nonadherence. METHODS: A
      descriptive comparative design was used. Descriptive statistics were used to
      define and compare the study population in terms of demographic data, which
      included age, gender, ethnicity, New York Heart Association heart failure
      classification, and comorbidities. Additionally, patients were surveyed to
      determine reasons for nonadherence to recommended overnight sleep study
      evaluation and or treatment with positive airway pressure. RESULTS: Demographics
      with higher percentages of adherence to evaluation and treatment included younger
      individuals and male gender. Prevalent reasons for nonadherence for evaluation
      and treatment included negative perceptions of an overnight sleep study
      evaluation and advanced age. IMPLICATIONS FOR PRACTICE: The community nurse
      educator can use the descriptive comparative findings in this study to tailor
      educational programs toward individuals with heart failure who have screened
      positive for SBD who are most at risk for nonadherence.

PMID- 23879579
TI  - Patient scenario identifies gaps in breast cancer services in a rural region.
AB  - Studies have demonstrated that community-based cancer coalitions can effectively
      address cancer disparities in rural areas. Scenario plots have been used to
      assess community needs in health care and public health. The social and medical
      context of a woman with undetected breast cancer was developed as a patient
      scenario implemented at a rural cancer coalition meeting to rapidly identify gaps
      in services. Transportation, fragmentation of cancer care, access to insurance
      coverage, patient navigation, and survivorship services were identified as gaps
      in ensuring patient compliance across the continuum of breast cancer care
      throughout the region. Results will be used to shape coalition priorities. 

PMID- 23879580
TI  - Administration of over-the-counter medication to children at home--a survey of
      parents from community health centers.
AB  - Parents (n = 135) were surveyed in relation to administering
      antipyretic/analgesic medications to their children (2 months-6 years) at home.
      Parents usually chose acetaminophen, calculated dosages based on weight but did
      not always know the child's weight, administered medications with a dropper, and
      reported having a sick child was moderately stressful. Many children were
      medicated for pain and/or fever during the week prior to immunization and many
      weighed more than the age/weight recommended dosages on the label. Community
      health nurses can facilitate safe administration of medications by integrating
      knowledge of parents' pain and fever management practices into discussions and
      anticipatory planning during clinic visits.

PMID- 23879581
TI  - Using simulation to teach child injury prevention to mothers recovering from
      substance abuse.
AB  - A paucity of literature regarding strategies for injury prevention in children
      for mothers with substance abuse exists. Substance abuse propagates distractions
      such as inattention; therefore, these mothers should be targeted for injury
      prevention education. A quasi-experimental design compared the results of
      traditional classroom teaching with an innovative home hazard simulation activity
      to teach injury prevention to mothers recovering from substance abuse. Study
      results identified a need to employ multiple modalities when teaching injury
      prevention. Information obtained from this research suggests a need for continued
      study and adaptation of current teaching strategies for injury prevention
      education in other high-risk populations. 

PMID- 23879582
TI  - Parenting and child outcomes of HIV-infected African American mothers: a
      literature review.
AB  - Parenting young children while living with HIV is an important public health
      concern. This article reviews maternal HIV and the impact it has on the parenting
      experience of African American mothers. Because living with HIV has been
      considered a family illness, the Family Systems Model provided a framework for
      this article. The model demonstrated an important link between maternal HIV and
      its impact on the health and wellbeing of not only the mother and her children,
      but her parenting and family roles as well. Research has documented an
      association between maternal HIV and negative parent-child outcomes among African
      American mothers. I examined studies on parenting and child outcomes among
      African American mothers living with HIV. The review assists in conceptualizing
      parenting with HIV as an area of increasing importance in health services
      delivery to HIV-infected African American mothers who are caring for young
      children. 

PMID- 23879584
TI  - Next-generation metal anticancer complexes: multitargeting via redox modulation.
AB  - Platinum complexes are widely used anticancer drugs. New generations of metal
      chemotherapeutics offer the prospect of combating platinum resistance and
      expanding the range of treatable cancers. Such new complexes might be effective
      if they form distinctly different lesions on DNA. In this Forum Article, we
      discuss the possibility that targeting the redox balance in cancer cells may also
      be a highly effective strategy, especially because it is a multiple-site approach
      and offers selectivity over normal cells. Metal complexes can interfere in
      cellular redox chemistry in several ways: directly through metal or ligand redox
      centers or indirectly by binding to biomolecules involved in cellular redox
      pathways. We illustrate that a surprisingly large number of active metal
      anticancer agents have a potential redox arm to their mechanism of action. For
      such complexes, the possibility arises of using combination therapy together with
      redox modulators to increase the anticancer potency: attractive for lowering the
      doses of metal complexes that need to be administered. We illustrate that
      organometallic ruthenium(II) and osmium(II) arene complexes and iridium(III)
      cyclopentadienyl complexes of the type [(arene/Cp(xPh))M(N,N)Cl/I](n+) can
      achieve nanomolar potency toward cancer cells in combination with the redox
      modulator l-buthionine sulfoximine. Our discussion highlights the importance of
      determining not only the distribution of metal anticancer complexes in cells but
      also their speciation, the chemical form of the metal complex, including the
      oxidation state of the metal, the fate of the ligands, and dynamic processes such
      as efflux. This will be aided in the future by proteomic and genomic analyses but
      needs to be supplemented by new analytical methods that have the sensitivity and
      spatial and temporal resolution to reveal such information. To achieve this,
      major new funding programs are needed that support global research on the design
      of novel metal-based drugs with new mechanisms of action, tailored to patient
      needs. 

PMID- 23879585
TI  - Fear of intimacy with helping professionals and its impact on elderly Chinese.
AB  - AIM: The present study aimed to investigate the attitudes of Chinese older adults
      toward seeking help from healthcare professionals, and its impact on their self
      care ability and medication adherence. METHODS: A cross-sectional study using a
      questionnaire survey was carried out. A convenience sample of 301 older adults
      was recruited from six health centers in Macao, People's Republic of China. The
      Chinese versions of Fear of Intimacy with Helping Professionals (C-FIHP),
      Exercise of Self-care Agency (C-ESCA) and Morisky 4-Item Self-Report Measure of
      Medication-Taking Behavior (C-MMAS) were used to measure the study variables.
      RESULTS: Chinese older adults who were married and had comorbidity with arthritis
      showed significantly negative attitudes toward seeking help form healthcare
      professional than those who were not married (P < 0.05) and did not have
      arthritis (P < 0.01). There are significant negative correlations between C-FIHP
      with C-ESCA (P < 0.01) and C-MMAS-4 (P < 0.01). Regression analysis identified
      three predicative factors of fear of intimacy with helping professionals: marital
      status, comorbidity with arthritis and self-care agency, which accounted for
      23.9% of variance. CONCLUSIONS: The present study suggests that Chinese older
      adults' fear of intimacy with helping professionals impacts their perceived self
      care ability and medication adherence. The three predictive factors identified in
      the present study might provide useful pointers for healthcare professionals to
      customize an effective approach to encourage and engage older adults. This might
      improve the self-care ability and medication adherence of older adults, which
      will result in a better quality of life and psychosocial well-being.

PMID- 23879586
TI  - Iron and hepatic carcinogenesis.
AB  - Iron is an essential co-factor for life; however, a physiologically optimal
      balance is critical. Too much or too little iron can have detrimental effects on
      human health. In this article, we explore the relationships between iron and
      hepatocellular carcinoma (HCC). Iron can act as a modulating co-factor in a range
      of chronic liver diseases and can accelerate the development of liver injury,
      fibrosis, cirrhosis, and ultimately HCC. Iron can, however, also act as a sole
      factor in the causation of liver cirrhosis and HCC in individuals with hereditary
      hemochromatosis (HH). We overview the regulation of normal iron metabolism and
      the role of iron in wound healing and associated cell types as well as in
      pathophysiologies that predispose to HCC. We review how these injury processes
      are inextricably linked, providing a mechanistic basis for understanding how iron
      and hepatic injury potentially result in HCC. 

PMID- 23879587
TI  - Iron chelation: inhibition of key signaling pathways in the induction of the
      epithelial mesenchymal transition in pancreatic cancer and other tumors.
AB  - Pancreatic cancer is the fourth leading cause of cancer-related deaths worldwide
      in both men and women. It presents late with non-specific symptoms, which makes
      it difficult to diagnose until the cancer has progressed and metastasized.
      Metastasis is facilitated by the epithelial-to-mes-enchymal transition (EMT),
      which is promoted via the oncogenic transforming growth factor beta (TGFbeta),
      Wnt, and nuclear factor kappa B (NFkappaB) signaling pathways. However, recent
      studies have demonstrated that the EMT can be inhibited by novel anti-cancer
      agents known as thiosemicarbazone iron chelators. These novel agents also up
      regulate the metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1),
      which can restore normal signaling to the cell and suppresses metastasis via
      inhibition of the EMT. Through the ability of iron chelators to up-regulate NDRG1
      expression and affect multiple molecular targets, these agents have the potential
      to maintain the epithelial phenotype of cancer cells and may lead to improved
      survival rates for patients with late-stage disease. 

PMID- 23879588
TI  - Cellular iron metabolism in prognosis and therapy of breast cancer.
AB  - Despite many recent advances, breast cancer remains a clinical challenge. Current
      issues include improving prognostic evaluation and increasing therapeutic options
      for women whose tumors are refractory to current frontline therapies. Iron
      metabolism is frequently disrupted in breast cancer, and may offer an opportunity
      to address these challenges. Iron enhances breast tumor initiation, growth and
      metastases. Iron may contribute to breast tumor initiation by promoting redox
      cycling of estrogen metabolites. Up-regulation of iron import and down-regulation
      of iron export may enable breast cancer cells to acquire and retain excess iron.
      Alterations in iron metabolism in macrophages and other cells of the tumor
      microenvironment may also foster breast tumor growth. Expression of iron
      metabolic genes in breast tumors is predictive of breast cancer prognosis. Iron
      chelators and other strategies designed to limit iron may have therapeutic value
      in breast cancer. The dependence of breast cancer on iron presents rich
      opportunities for improved prognostic evaluation and therapeutic intervention. 

PMID- 23879590
TI  - Iron in Hodgkin's lymphoma.
AB  - Anemia is a frequent finding of Hodgkin's lymphoma (HL) diagnosis. It is usually
      mild, with hemoglobin levels between 10 and 12 g/dl; it is rarely (<10% of cases)
      a result of bone marrow infiltration; and it displays the characteristics of the
      anemia of chronic disease due to abnormalities in iron metabolism. The
      inflammatory cytokine IL-6 is frequently up-regulated in Hodgkin's lymphoma, and
      IL-6 levels are strongly associated with hepcidin, the main regulator of iron
      metabolism. Elevated hepcidin levels result in iron restriction and signs of
      anemia of chronic disease. In addition, the abundant microenvironment surrounding
      the neoplastic Hodgkin's and Reed-Sternberg cells may contribute to alterations
      in iron metabolism. Tumor-infiltrating macrophages can sequester iron using
      scavenger receptors. Iron-restricted anemia at HL diagnosis can be aggravated by
      intensive chemotherapy, and iron overload may become clinically relevant in
      heavily treated patients with relapsed or refractory disease undergoing high-dose
      chemotherapy and stem cell transplantation. 

PMID- 23879589
TI  - Iron in multiple myeloma.
AB  - Multiple myeloma is a non-curable B-cell malignancy in which iron metabolism
      plays an important role. Patients with this disorder almost universally suffer
      from clinically significant anemia, which is often symptomatic, and which is due
      to impaired iron utilization. Recent studies have indicated that the proximal
      cause of dysregulated iron metabolism and anemia in these patients is cytokine
      induced upregulation of hepcidin expression. Malignant myeloma cells are
      dependent on an increased influx of iron, and therapeutic efforts are being made
      to target this requirement. The studies detailing the characteristics and
      biochemical abnormalities in iron metabolism causing anemia and the initial
      attempts to target iron therapeutically are described in this review. 

PMID- 23879591
TI  - Iron, erythropoietic stimulating agents, and anemia in cancer.
AB  - Anemia commonly accompanies malignancies in patients and may contribute to
      morbidity. Correction of the anemia with erythropoietic stimulating agents, while
      possible, may be associated with complications such as tumor progression and
      adverse cardiovascular events. This review examines the data behind these
      concerns and raises the strategy of using iron, alone, in the setting of cancer
      associated anemia to reduce exposure to transfusions in these patients and to
      potentially improve their quality of life. 

PMID- 23879592
TI  - Preface: iron and cancer.

PMID- 23879593
TI  - Gender differences in predictors of colorectal cancer screening uptake: a
      national cross sectional study based on the health belief model.
AB  - BACKGROUND: Colorectal Cancer (CRC) is rapidly rising in Asia, but screening
      uptake remains poor. Although studies have reported gender differences in
      screening rates, there have been few studies assessing gender specific
      perceptions and barriers towards CRC screening, based on behavioral frameworks.
      We applied the Health Belief Model to identify gender-specific predictors of CRC
      screening in an Asian population. METHODS: A nationwide representative household
      survey was conducted on 2000 subjects aged 50 years and above in Singapore from
      2007 to 2008. Screening behaviour, knowledge and beliefs on CRC screening were
      assessed by face-to-face structured interviews. The response rate was 88.2%.
      RESULTS: 26.7 percent had undergone current CRC screening with no gender
      difference in rates. Almost all agreed that CRC would lead to suffering (89.8%),
      death (84.6%) and would pose significant treatment cost and expense (83.1%). The
      majority (88.5%) agreed that screening aids early detection and cure but only
      35.4% felt susceptible to CRC. Nearly three-quarters (74.3%) of the respondents
      recalled reading or hearing information on CRC in the print or broadcast media.
      However, only 22.6% were advised by their physicians to undergo screening.
      Significantly more women than men had feared a positive diagnosis, held
      embarrassment, pain and risk concerns about colonoscopy and had friends and
      family members who encouraged screening. On multivariate analysis, screening
      uptake showed a positive association with worry about contracting CRC and a
      physician's recommendation and a negative association with perceived pain about
      colonoscopy for both genders. For women only, screening was positively associated
      with having attended a public talk on CRC and having a family member with CRC,
      and was negatively associated with Malay race and perceived danger of
      colonoscopy. CONCLUSIONS: CRC screening remains poor despite high levels of
      awareness of its benefits in this Asian population. Race, worry about contracting
      cancer, psychological barriers, and cues from the doctor and a public talk on CRC
      were associated with screening with gender specific differences. Strategies to
      increase CRC screening uptake should consider gender specific approaches to
      address psychological barriers and increase disease susceptibility through public
      health education and active promotion by physicians.

PMID- 23879594
TI  - The investigation of the possible relationship between Coxsackie viruses and
      pemphigus.
AB  - BACKGROUND: Pemphigus is a group of autoimmune bullous diseases on which the
      etiopathogenesis of several viruses has been blamed. Coxsackie viruses (CVs) are
      the causative agents of hand, foot, and mouth disease, and herpangina, which have
      been strongly associated with several autoimmune diseases. The onset of pemphigus
      after CV infection and cephalosporin use has been reported. OBJECTIVE: To detect
      the presence of CV in patients with pemphigus. MATERIALS AND METHODS: Reverse
      transcriptase-polymerase chain reaction analysis for CV RNA sequences and
      immunohistochemical staining for the CV and adenovirus receptor expression were
      performed on patient skin samples. CV-IgM and -IgG serum levels were analyzed.
      RESULTS: Thirty-two patients and 40 controls were investigated. Neither the CV
      and adenovirus receptor expression nor CV RNA sequences was established in the
      skin samples of patients. The ratio of CV-IgG positivity was higher in patients
      (12.5%) than in the controls (5%; P > 0.05). CONCLUSION: Our preliminary results
      indicate that the viral genome of CV does not become persistent in the skin.
      Further studies with a larger number of cases are needed to clarify the place of
      CVs in the etiopathogenesis of pemphigus.

PMID- 23879595
TI  - Characterization of total and active matrix metalloproteinases-1, -3, and -13
      synthesized and secreted by anterior cruciate ligament fibroblasts in three
      dimensional collagen gels.
AB  - Anterior cruciate ligament (ACL) injury and subsequent reconstructive surgery is
      increasing with an estimated 200,000 reconstructions performed yearly in the
      United States. Current treatment requires reconstruction with autograft or
      allograft tissue with inherent disadvantages. The development of tissue
      engineered ligament replacements or scaffolds may provide an alternative
      treatment method minimizing these issues. The study of ligament fibroblast
      catabolic and anabolic responses to mechanical and biologic stimuli in three
      dimensional (3D) cell culture systems is critical to the development of such
      therapies. A 3D cell culture system was used to measure the total content and
      active forms of matrix metalloproteinases (MMPs)-1, -3, and -13 to assess the
      potential role of the mechanical environment in regulation of matrix turnover by
      ligament fibroblasts. The production, retention, and secretion of MMPs by ACL
      fibroblasts in 3D culture were measured over a 14-day period. The total MMP
      content and MMP activity were determined. The level of all MMPs studied increased
      over 7-10 days and then reached a steady state or decreased slightly in both the
      collagen gels and the media. This system will now permit the study of externally
      applied cyclic and static strains, strain deprivation, and the potential combined
      role of the cytoskeleton and MMPs in matrix turnover in ligaments. 

PMID- 23879596
TI  - A functional glycogen biosynthesis pathway in Lactobacillus acidophilus:
      expression and analysis of the glg operon.
AB  - Glycogen metabolism contributes to energy storage and various physiological
      functions in some prokaryotes, including colonization persistence. A role for
      glycogen metabolism is proposed on the survival and fitness of Lactobacillus
      acidophilus, a probiotic microbe, in the human gastrointestinal environment. L.
      acidophilus NCFM possesses a glycogen metabolism (glg) operon consisting of
      glgBCDAP-amy-pgm genes. Expression of the glg operon and glycogen accumulation
      were carbon source- and growth phase-dependent, and were repressed by glucose.
      The highest intracellular glycogen content was observed in early log-phase cells
      grown on trehalose, which was followed by a drastic decrease of glycogen content
      prior to entering stationary phase. In raffinose-grown cells, however, glycogen
      accumulation gradually declined following early log phase and was maintained at
      stable levels throughout stationary phase. Raffinose also induced an overall
      higher temporal glg expression throughout growth compared with trehalose.
      Isogenic DeltaglgA (glycogen synthase) and DeltaglgB (glycogen-branching enzyme)
      mutants are glycogen-deficient and exhibited growth defects on raffinose. The
      latter observation suggests a reciprocal relationship between glycogen synthesis
      and raffinose metabolism. Deletion of glgB or glgP (glycogen phosphorylase)
      resulted in defective growth and increased bile sensitivity. The data indicate
      that glycogen metabolism is involved in growth maintenance, bile tolerance and
      complex carbohydrate utilization in L. acidophilus. 

PMID- 23879600
TI  - Tattoos and human identification: investigation into the use of X-ray and
      infrared radiation in the visualization of tattoos.
AB  - Any person with a tattoo known to their family or friends could potentially be
      identified from the presence of such personal identifying markers. Problems in
      identification utilizing tattoos may arise when these markers are removed or
      defaced in some way. This paper uses infrared wavelengths at 760, 850, and 950 nm
      to improve the visualization of laser-removed or covered up tattoos and also to
      establish whether the ink pigments used can be observed on radiographs from any
      metal that may be present. The results obtained indicate that some older inks
      have a high enough metallic content to allow them to be viewed on a radiograph,
      while infrared light can demonstrate latent ink still present in the skin after
      laser removal and can also be utilized to distinguish an original tattoo through
      a secondary "cover-up" tattoo. Infrared photography and radiography have been
      shown to improve tattoo visualization in a forensic context. 

PMID- 23879599
TI  - Traumatic brain injury: methodological approaches to estimate health and economic
      outcomes.
AB  - The effort to standardize the methodology and adherence to recommended principles
      for all economic evaluations has been emphasized in medical literature. The
      objective of this review is to examine whether economic evaluations in traumatic
      brain injury (TBI) research have been compliant with existing guidelines. Medline
      search was performed between January 1, 1995 and August 11, 2012. All original
      TBI-related full economic evaluations were included in the study. Two authors
      independently rated each study's methodology and data presentation to determine
      compliance to the 10 methodological principles recommended by Blackmore et al.
      Descriptive analysis was used to summarize the data. Inter-rater reliability was
      assessed with Kappa statistics. A total of 28 studies met the inclusion criteria.
      Eighteen of these studies described cost-effectiveness, seven cost-benefit, and
      three cost-utility analyses. The results showed a rapid growth in the number of
      published articles on the economic impact of TBI since 2000 and an improvement in
      their methodological quality. However, overall compliance with recommended
      methodological principles of TBI-related economic evaluation has been deficient.
      On average, about six of the 10 criteria were followed in these publications, and
      only two articles met all 10 criteria. These findings call for an increased
      awareness of the methodological standards that should be followed by
      investigators both in performance of economic evaluation and in reviews of
      evaluation reports prior to publication. The results also suggest that all
      economic evaluations should be made by following the guidelines within a
      conceptual framework, in order to facilitate evidence-based practices in the
      field of TBI.

PMID- 23879601
TI  - A resistant case of pemphigus gestationis successfully treated with intravenous
      immunoglobulin plus cyclosporine.

PMID- 23879602
TI  - Flexible three-dimensional SnO2 nanowire arrays: atomic layer deposition-assisted
      synthesis, excellent photodetectors, and field emitters.
AB  - Flexible three-dimensional SnO2 nanowire arrays were synthesized on a carbon
      cloth template in combination with atomic layer deposition and vapor transport.
      The as-grown nanostructures were assembled by high density quasi-aligned
      nanowires with a large aspect ratio. Nanoscale photodetectors based on the
      flexible nanostructure demonstrate excellent ultraviolet light selectivity, a
      high speed response time less than 0.3 s, and dark current as low as 2.3 pA.
      Besides, field emission measurements of the hierarchical structure show a rather
      low turn-on field (3.3 VMUm(-1)) and threshold field (4.5 VMUm(-1)), as well as
      an excellent field enhancment factor (2375) with a long-term stability up to 20
      h. These results indicate that the flexible three-dimensional SnO2 nanowire
      arrays can be used as functional building blocks for efficient photodetectors and
      field emitters. 

PMID- 23879603
TI  - Carbapenemases: a worldwide threat.

PMID- 23879604
TI  - Personalized medicine in sepsis: the coming of age.

PMID- 23879605
TI  - Dose-ranging activity of the newly registered antituberculosis drug bedaquiline
      (TMC207).
AB  - Evaluation of: Diacon AH, Dawson R, Von Groote-Bidlingmaier F et al. Randomized
      dose-ranging study of the 14-day early bactericidal activity of bedaquiline
      (TMC207) in patients with sputum microscopy smear-positive pulmonary
      tuberculosis. Antimicrob. Agents Chemother. 57(5), 2199-2203 (2013). During the
      past decade considerable efforts have been made to develop and register new anti
      TB drugs, making them available for patients in need. Bedaquiline (BDQ), approved
      by the US FDA in December 2012, is the first new anti-TB drug available for
      treatment of this disease since rifampicin became available in 1967. BDQ has the
      peculiarity of being a drug with a very long half-life and potent antimicrobial
      activity that becomes noticeable only after the first 4 days of treatment.
      Consequently, Diacon et al. have conducted a 14-day dose-ranging study aimed at
      assessing the early bactericidal activity of BDQ in TB patients who received
      loading doses of the drug during the first 2 days of treatment. The loading doses
      partially overcame the delayed antimicrobial activity only in patients treated
      daily with as much as 400 mg. 

PMID- 23879607
TI  - Current status of carbapenemases in Latin America.
AB  - Enterobacteriaceae and non fermenting Gram-negative bacilli have become a threat
      to public health, in part due to their resistance to multiple antibiotic classes,
      which ultimately have led to an increase in morbidity and mortality. beta-lactams
      are currently the mainstay for combating infections caused by these
      microorganisms, and beta-lactamases are the major mechanism of resistance to this
      class of antibiotics. Within the beta-lactamases, carbapenemases pose one of the
      gravest threats, as they compromise one of our most potent lines of defense, the
      carbapenems. Carbapenemases are being continuously identified worldwide; and in
      Latin America, numerous members of these enzymes have been reported. In this
      region, the high incidence of reports implies that carbapenemases have become a
      menace and that they are an issue that must be carefully studied and analyzed. 

PMID- 23879609
TI  - Lactoferrin and the newborn: current perspectives.
AB  - Neonatal sepsis and necrotizing enterocolitis (NEC) are associated with
      significant mortality and morbidity. Inflammation secondary to sepsis and NEC
      increases morbidity, especially those related to the lung, brain and eye.
      Therapeutic strategies that target inflammation and decrease the emergence of
      antibiotic resistance are urgently needed. Lactoferrin (Lf) is a multifunctional
      protein that modulates inflammation, cell growth and differentiation and has
      broad antimicrobial activity. Studies evaluating the efficacy and safety of Lf in
      the prevention of neonatal sepsis and NEC are currently in progress, and one
      completed study shows significant promise. In this article, the functions of this
      multifunctional molecule and current clinical evidence for its use in the newborn
      are reviewed. Lf prophylaxis and therapy may have a significant impact in
      improving clinical outcomes of vulnerable preterm neonates. 

PMID- 23879610
TI  - Toward the elimination of lymphatic filariasis by 2020: treatment update and
      impact assessment for the endgame.
AB  - Lymphatic filariasis (LF) is an important public health problem endemic in 73
      countries, where it is a major cause of acute and chronic morbidity and a
      significant impediment to socioeconomic development. It is targeted for
      elimination by 2020, through preventive chemotherapy using albendazole in
      combination with either ivermectin or diethylcarbamazine citrate. Preventive
      chemotherapy enables the regular and coordinated administration of safe, single
      dose medications delivered through mass drug administration (MDA). Many countries
      are now scaling down MDA activities after achieving 100% geographic coverage and
      instituting monitoring and evaluation procedures to establish the impact of
      several consecutive rounds of MDA and determine if transmission has been
      interrupted. At the same time, countries yet to initiate MDA for elimination of
      LF will adopt improved mapping and coverage assessment protocols to accelerate
      the efforts for achieving global elimination by 2020. This review provides an
      update on treatment for LF and describes the current global status of the
      elimination efforts, transmission control processes and strategies for measuring
      impact and continuing surveillance after MDA has ceased. 

PMID- 23879611
TI  - Advocacy, policies and practicalities of preventive chemotherapy campaigns for
      African children with schistosomiasis.
AB  - Preventive chemotherapy campaigns against schistosomiasis have progressively
      scaled-up during the last decade, administering single standard dose praziquantel
      (40 mg/kg) treatments to millions of African children. Steps taken in securing
      international advocacy and national level implementation are traced to highlight
      an international treatment platform set for further expansion, including
      surveillance of schistosomiasis, school-level targeting with better on-site drug
      administration and annual reporting of programmatic indicators (i.e., treatment
      coverage), potentially in real-time. Several shortcomings in need of resolution
      are identified and efficacy of praziquantel is assessed by a systematic review.
      If WHO predictions in reduction of schistosomiasis are to be realized, careful
      international harmonization and tailoring of national resources are required.
      Maintaining an effective drug distribution system and regularly checking drug
      efficacy are paramount. 

PMID- 23879612
TI  - Energetics and hierarchical interactions of metal-phthalocyanines adsorbed on
      graphene/Ir(111).
AB  - The adsorption of metal-phthalocyanine (MPc) layers (M = Fe, Co, Cu) assembled on
      graphene/Ir(111) is studied by means of temperature-programmed X-ray
      photoemission spectroscopy (XPS) and near-edge X-ray absorption fine structure
      (NEXAFS). The balance between interaction forces among the organometallic
      molecules and the underlying graphene gives rise to flat-lying molecular layers,
      weakly interacting with the underlying graphene. Further MPc layers pile up face
      on onto the first layer, up to a few nanometers thickness, as deduced by NEXAFS.
      The FePc, CoPc, and CuPc multilayers present comparable desorption temperatures,
      compatible with molecule-molecule interactions dominated by van der Waals forces
      between the pi-conjugated macrocycles. The MPc single layers desorb from
      graphene/Ir at higher temperatures. The CuPc single layer desorbs at lower
      temperature than the FePc and CoPc single layers, suggesting a higher adsorption
      energy of the FePc and CoPc single layers on graphene/Ir with respect to CuPc,
      with increasing molecule-substrate interaction in the order E(CuPc) < E(FePc) ~
      E(CoPc).

PMID- 23879608
TI  - Photodynamic inactivation of biofilm: taking a lightly colored approach to
      stubborn infection.
AB  - Microbial biofilms are responsible for a variety of microbial infections in
      different parts of the body, such as urinary tract infections, catheter
      infections, middle-ear infections, gingivitis, caries, periodontitis, orthopedic
      implants, and so on. The microbial biofilm cells have properties and gene
      expression patterns distinct from planktonic cells, including phenotypic
      variations in enzymic activity, cell wall composition and surface structure,
      which increase the resistance to antibiotics and other antimicrobial treatments.
      There is consequently an urgent need for new approaches to attack biofilm
      associated microorganisms, and antimicrobial photodynamic therapy (aPDT) may be a
      promising candidate. aPDT involves the combination of a nontoxic dye and low
      intensity visible light which, in the presence of oxygen, produces cytotoxic
      reactive oxygen species. It has been demonstrated that many biofilms are
      susceptible to aPDT, particularly in dental disease. This review will focus on
      aspects of aPDT that are designed to increase efficiency against biofilms
      modalities to enhance penetration of photosensitizer into biofilm, and a
      combination of aPDT with biofilm-disrupting agents. 

PMID- 23879613
TI  - Effects of leg dominance on performance of ballet turns (pirouettes) by
      experienced and novice dancers.
AB  - Turns (pirouettes) are an important movement in ballet and may be affected by
      "lateral bias". This study investigated physiological differences exhibited by
      experienced and novice dancers, respectively, when performing pirouette with
      dominant and non-dominant leg supports, respectively. Thirteen novice and 13
      experienced dancers performed turns on dominant or non-dominant legs. The maximum
      ankle plantarflexion, knee extension and hip extension were measured during the
      single-leg support phase. The inclination angle of rotation axis is the angle
      between instantaneous rotation axis and global vertical axis in the early single
      leg support phase. Both groups exhibited a greater hip extension, knee extension,
      and ankle plantarflexion when performing a turn on the non-dominant leg. For
      experienced dancers, the inclination angle of rotation axis during the pre-swing
      phase was generally smaller for dominant leg support than non-dominant leg.
      However, no significant difference was found in inclination angle of rotation
      axis of novice dancers. For experienced dancers, an improved performance is
      obtained when using the dominant leg for support. By contrast, for novice
      dancers, the performance is independent of choice of support leg. The significant
      lateral bias in experienced dancers indicates the possible influence of training.
      That is, repetitive rehearsal on the preferred leg strengthens the impact of side
      dominance in experienced dancers. 

PMID- 23879614
TI  - Chukfuransins A-D, four new phragmalin limonoids with beta-furan ring involved in
      skeleton reconstruction from Chukrasia tabularis.
AB  - Four new phragmalin limonoids (chukfuransins A-D) were isolated from the twigs
      and leaves of Chukrasia tabularis. Chukfuransins A (1) and B (2) feature a unique
      C-15/C-20 linkage proposed to be built by a biogenetic pathway involving Michael
      addition. Chukfuransins C (3) and D (4) feature the C-15/C-21 linkage. Their
      structures and absolute configurations were established by NMR techniques and X
      ray crystallographic analysis. 

PMID- 23879615
TI  - Marginal bone preservation in single-tooth replacement: a 5-year prospective
      clinical multicenter study.
AB  - BACKGROUND: Few long-term studies are available comparing immediate and
      conventional loading protocols of implant-supported single-tooth replacement.
      PURPOSE: The aim of the present randomized controlled clinical trial was to
      evaluate prospectively the 5-year clinical and radiological outcome of immediate
      functional loading implants used in single-tooth replacement. MATERIALS AND
      METHODS: One hundred fifty-one subjects, who required single-tooth rehabilitation
      in the area from position 15 to 25 and from 35 to 45, were enrolled in eight
      private clinics in Italy. A randomization protocol was applied to allocate the
      implants in three treatment groups: one control group and two test groups. In the
      control group, implant placement was performed according to a conventional
      drilling procedure, and the implants were submerged for 3 months before abutment
      connection and loading. Implants allocated in the test group 1 and 2 followed an
      immediate functional loading protocol. While in test group 1, implant placement
      was performed according to conventional drilling procedure, in test group 2, a
      modified implant installation procedure (osteotome technique) was applied.
      Clinical and radiographic examinations were performed during the 5-year follow
      up, and technical and biological complications were registered. RESULTS: Although
      four implants (three in the test group 2 and one in the test group 1) were lost
      in the immediate functional loading groups in the first year of follow-up, no
      further implant loss occurred in any of the treatment groups in the following
      monitoring period up to 5 years. No significant differences on marginal bone
      level changes were observed between the treatment groups. About 52% of all
      implants showed bone gain in the period from 1-year to 5-year follow-up. The
      percentage of all implants that in the same interval of time showed bone loss was
      about 28%. Although few technical complications were recorded in the period of
      time up to 5 years, implants showing biological complication were 5.7%.
      CONCLUSION: It is suggested that implants installed with a conventional
      installation technique together with an immediate functional loading protocol may
      be considered as a valid treatment alternative in a long-term perspective when
      used in a single-tooth replacement in an esthetic area.

PMID- 23879616
TI  - Clinical analysis and classification of dark eye circle.
AB  - BACKGROUND: Dark eye circle (DEC) is a common problem that usually lacks detailed
      classification in the etiology and structural variations. A newly-developed DEC
      Assessment Score using Wood's lamp and ultrasonogram will provide a more precise
      evaluation of DEC for improving treatment results. MATERIALS AND METHODS: Sixty
      five cases, including eight males and 57 females with a mean age of 38.9 years,
      were enrolled. DEC were classified into pigmented (brown), vascular (blue to
      purple), structural, and mixed type by Wood's lamp and ultrasonogram. A scoring
      system with nine parameters, including brown hue, pigmented lesions,
      blue/pink/purple hue, periorbital puffiness, shadow hue, infraorbital palpebral
      bags, infraorbital grooves, blepharoptosis, and skin type, was used for clinical
      evaluation. RESULTS: Pigmented, vascular, structural, and mixed types of DEC
      represented 5%, 14%, 3%, and 78%, respectively. Thirty-three cases with
      periorbital puffiness were found to have higher "pre-septal thickness" than those
      of 20 controlled cases (P = 0.032). Fourteen patients with infraorbital palpebral
      bags were proved to have protruded retroseptal fat pads by ultrasonography.
      CONCLUSION: Pigmentation and vascular and structural components may play
      important roles in DEC. Detailed classification of DEC types will access
      physicians in the decision of appropriate therapeutic modalities.

PMID- 23879617
TI  - Identifying functional networks using endogenous connectivity in gamma band
      electrocorticography.
AB  - Correlations in spontaneous, infra-slow (<0.1 Hz) fluctuations in gamma band (70
      100 Hz) signal recorded using electrocorticography (ECoG) reflect the functional
      organization of the brain, appearing in auditory and visual sensory cortex, motor
      cortex, and the default mode network (DMN). We have developed a data-driven
      method using co-modulation in spontaneous, infra-slow, and gamma band power
      fluctuations in ECoG to characterize the connectivity between cortical areas. A
      graph spectral clustering algorithm was used to identify networks that appear
      consistently. These networks were compared with clinical mapping results obtained
      using electrocortical stimulation (ECS). We identify networks corresponding to
      motor and visual cortex with good specificity. Anatomic and functional evidence
      indicates that other networks, such as the DMN, are also identified by this
      algorithm. These results indicate that it may be possible to map functional
      cortex using only spontaneous ECoG recordings. In addition, they support the
      hypothesis that infra-slow co-modulations of gamma band power represent the
      neurophysiological basis underlying resting-state networks. Methods examining
      infra-slow co-modulations in gamma band power will be useful for studying changes
      in brain connectivity in differing behavioral contexts. Our observations can be
      made in the absence of observable behavior, suggesting that the electrical
      mapping of functional cortex is feasible without the use of ECS or task-mediated
      evoked responses.

PMID- 23879618
TI  - Parallel analysis of finite element model controlled trial and retrospective case
      control study on percutaneous internal fixation for vertical sacral fractures.
AB  - BACKGROUND: Although percutaneous posterior-ring tension-band metallic plate and
      percutaneous iliosacral screws are used to fix unstable posterior pelvic ring
      fractures, the biomechanical stability and compatibility of both internal
      fixation techniques for the treatment of Denis I, II and III type vertical sacral
      fractures remain unclear. METHODS: Using CT and MR images of the second
      generation of Chinese Digitized Human "male No. 23", two groups of finite element
      models were developed for Denis I, II and III type vertical sacral fractures with
      ipsilateral superior and inferior pubic ramus fractures treated with either a
      percutaneous metallic plate or a percutaneous screw. Accordingly, two groups of
      clinical cases that were fixed using the above-mentioned two internal fixation
      techniques were retrospectively evaluated to compare postoperative effect and
      function. Parallel analysis was performed with a finite element model controlled
      trial and a case control study. RESULTS: The difference of the postoperative
      Majeed standards and outcome rates between two case groups was no statistically
      significant (P > 0.05). Accordingly, the high values of the maximum
      displacements/stresses of the plate-fixation model group approximated those of
      the screw-fixation model group. However, further simulation of Denis I, II and
      III type fractures in each group of models found that the biomechanics of the
      plate-fixation models became increasingly stable and compatible, whereas the
      biomechanics of the screw-fixation models maintained tiny fluctuations. When
      treating Denis III fractures, the biomechanical effects of the pelvic ring of the
      plate-fixation model were better than the screw-fixation model. CONCLUSIONS:
      Percutaneous plate and screw fixations are both appropriate for the treatment of
      Denis I and II type vertical sacral fractures; whereas percutaneous plate
      fixation appears be superior to percutaneous screw fixation for Denis III type
      vertical sacral fracture. Biomechanical evidence of finite element evaluations
      combined with clinical evidence will contribute to our ability to distinguish
      between indications that require plate or screw fixation for vertical sacral
      fractures.

PMID- 23879619
TI  - Leptin and plasminogen activator inhibitor-1 levels in children on chronic
      dialysis.
AB  - PURPOSE: In this study, it is aimed to compare the serum leptin and PAI-1 levels
      and evaluate their relationship in children on hemodialysis (HD) and peritoneal
      dialysis (PD). METHOD: Thirty-six patients on HD (mean age: 15.0 +/- 2.8 years),
      19 patients on PD (mean age: 13.0 +/- 3.5 years) and 15 healthy subjects (mean
      age: 14.5 +/- 2.7 years) were included in the study. Laboratory investigations
      included blood count, biochemical parameters, serum iron, iron binding capacity,
      parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP),
      prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum
      leptin and PAI-1 levels. RESULTS: Serum leptin levels were significantly higher
      in HD group than in control group when the effects of BMI and sex were
      controlled, while PD and control groups had similar leptin levels. PAI-1 levels
      were also significantly higher in HD group than in control group, while there was
      no statistically significant difference in PAI-1 levels of PD and control group.
      PAI-1 levels and leptin levels were significantly correlated, which was
      independent of the effect of BMI in both HD and PD groups when they are evaluated
      separately. CONCLUSION: Results of our study showed that HD patients had higher
      leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly
      in both patient groups. The effect of elevated serum leptin and PAI-1 levels on
      the cardiovascular complications remains to be established.

PMID- 23879620
TI  - Modulation of ENaC, CFTR, and iNOS expression in bronchial epithelial cells after
      stimulation with Staphylococcus epidermidis (94B080) and Staphylococcus aureus
      (90B083).
AB  - Bacteria affect the respiratory epithelium, which is covered by airway surface
      liquid (ASL) and mucus. Ion concentrations in the ASL are determined by the
      cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial
      Na(+) channel (ENaC). Neonatal sepsis is a major risk factor for subsequent
      pulmonary disease in preterm newborns. Predominating are coagulase-negative
      staphylococci (e.g., Staphylococccus epidermidis and Staphylococccus aureus). The
      aim of this study was to investigate modulation of CFTR, ENaC, mucins,
      proinflammatory cytokines, and inducible nitric oxide synthase (iNOS) in
      respiratory epithelial cells after S. epidermidis 94B080 and S. aureus 90B083
      exposure. Bronchial epithelial cells were incubated with S. epidermidis 94B080
      and S. aureus 90B083 (neonatal blood isolates) for 1-36 h. Expression of CFTR,
      ENaC, iNOS, and mucins was analyzed by real-time PCR and Western blotting.
      Release of cytokines was analyzed by ELISA, and production of NO by the Griess
      assay. Expression of CFTR significantly decreased after 36 h incubation with S.
      epidermidis and more prominently with S. aureus, whereas S. epidermidis caused a
      significant increase in the expression of beta- and gamma-ENaC. Expression of
      iNOS increased, but NO was not detected. Both staphylococci caused a decrease in
      the intracellular Ca(2+) concentration. S. aureus induced increased secretion of
      IL-6, IL-8, and transforming nuclear factor (TNF)-alpha in a time-dependent
      manner as compared with S. epidermidis. In conclusion, expression of ENaC, CFTR,
      and iNOS is modulated by exposure to S. aureus 90B083 and S. epidermidis 94B080.
      S. aureus is more potent in causing release of IL-6, IL-8, and TNF-alpha by
      bronchial epithelial cells as compared with S. epidermidis. The mRNA expression
      for the mucus proteins MUC2, MUC5AC, and MUC5B could not be measured, neither in
      the presence nor in the absence of bacteria.

PMID- 23879622
TI  - Nitrogen-doped graphene sheets grown by chemical vapor deposition: synthesis and
      influence of nitrogen impurities on carrier transport.
AB  - A significant advance toward achieving practical applications of graphene as a
      two-dimensional material in nanoelectronics would be provided by successful
      synthesis of both n-type and p-type doped graphene. However, reliable doping and
      a thorough understanding of carrier transport in the presence of charged
      impurities governed by ionized donors or acceptors in the graphene lattice are
      still lacking. Here we report experimental realization of few-layer nitrogen
      doped (N-doped) graphene sheets by chemical vapor deposition of organic molecule
      1,3,5-triazine on Cu metal catalyst. When reducing the growth temperature, the
      atomic percentage of nitrogen doping is raised from 2.1% to 5.6%. With increasing
      doping concentration, N-doped graphene sheet exhibits a crossover from p-type to
      n-type behavior accompanied by a strong enhancement of electron-hole transport
      asymmetry, manifesting the influence of incorporated nitrogen impurities. In
      addition, by analyzing the data of X-ray photoelectron spectroscopy, Raman
      spectroscopy, and electrical measurements, we show that pyridinic and pyrrolic N
      impurities play an important role in determining the transport behavior of
      carriers in our N-doped graphene sheets. 

PMID- 23879621
TI  - Comparison of uncultured marrow mononuclear cells and culture-expanded
      mesenchymal stem cells in 3D collagen-chitosan microbeads for orthopedic tissue
      engineering.
AB  - Stem cell-based therapies have shown promise in enhancing repair of bone and
      cartilage. Marrow-derived mesenchymal stem cells (MSC) are typically expanded in
      vitro to increase cell number, but this process is lengthy, costly, and there is
      a risk of contamination and altered cellular properties. Potential advantages of
      using fresh uncultured bone marrow mononuclear cells (BMMC) include heterotypic
      cell and paracrine interactions between MSC and other marrow-derived cells
      including hematopoietic, endothelial, and other progenitor cells. In the present
      study, we compared the osteogenic and chondrogenic potential of freshly isolated
      BMMC to that of cultured-expanded MSC, when encapsulated in three-dimensional
      (3D) collagen-chitosan microbeads. The effect of low and high oxygen tension on
      cell function and differentiation into orthopedic lineages was also examined.
      Freshly isolated rat BMMC (25 * 10(6) cells/mL, containing an estimated 5 * 10(4)
      MSC/mL) or purified and culture-expanded rat bone marrow-derived MSC (2 * 10(5)
      cells/mL) were added to a 65-35 wt% collagen-chitosan hydrogel mixture and
      fabricated into 3D microbeads by emulsification and thermal gelation. Microbeads
      were cultured in control MSC growth media in either 20% O2 (normoxia) or 5% O2
      (hypoxia) for an initial 3 days, and then in control, osteogenic, or chondrogenic
      media for an additional 21 days. Microbead preparations were evaluated for
      viability, total DNA content, calcium deposition, and osteocalcin and sulfated
      glycosaminoglycan expression, and they were examined histologically. Hypoxia
      enhanced initial progenitor cell survival in fresh BMMC-microbeads, but it did
      not enhance osteogenic potential. Fresh uncultured BMMC-microbeads showed a
      similar degree of osteogenesis as culture-expanded MSC-microbeads, even though
      they initially contained only 1/10th the number of MSC. Chondrogenic
      differentiation was not strongly supported in any of the microbead formulations.
      This study demonstrates the microbead-based approach to culturing and delivering
      cells for tissue regeneration, and suggests that fresh BMMC may be an alternative
      to using culture-expanded MSC for bone tissue engineering.

PMID- 23879623
TI  - The expanding roles of 1-methyl-tryptophan (1-MT): in addition to inhibiting
      kynurenine production, 1-MT activates the synthesis of melatonin in skin cells.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1), the rate-limiting enzyme of tryptophan
      catabolism, has been strongly associated with the progression of malignancy and
      poor survival in melanoma patients. As a result, IDO1 is a leading target for
      interventions aimed at restoring melanoma immune surveillance. Here, in a
      scenario involving the tryptophan catabolism, we report that melatonin
      biosynthesis is driven by 1-methyl-tryptophan (1-MT), a competitive inhibitor of
      IDO1, in human fibroblasts, melanocytes and melanoma cells. In addition to
      melatonin biosynthesis, 1-MT induced the expression of tryptophan hydroxylase,
      arylalkylamine-N-acetyltransferase and hydroxyindole O-methyltransferase mRNA in
      fibroblasts and melanocytes. We observed a great variability in the levels of
      IDO1 mRNA expression and kynurenine release between skin cells and melanoma cell
      lines in response to interferon-gamma, a classical IDO1 inducer. In this setting,
      melatonin was shown to downregulate kynurenine production. Furthermore, in a
      condition of low basal activity of IDO1, it was observed that 1-MT, as well
      melatonin, inhibited the proliferation of human melanoma cells. Taken together,
      our results suggest that 1-MT may serve as more than just a tool to disrupt tumor
      immune escape (via the inhibition of IDO1) because it was shown to act directly
      on the proliferation of human melanoma cells and induce melatonin biosynthesis in
      the tumor milieu. Moreover, 1-MT-mediated inhibition of IDO occurs in normal skin
      and melanoma cells, which addresses the possibility that all cells in the skin
      microenvironment can be targeted by 1-MT. Our findings provide innovative
      approaches into understanding tumor therapy related to the control of tryptophan
      metabolism by 1-MT. 

PMID- 23879624
TI  - Molecular phylogeny of marine gregarine parasites (Apicomplexa) from tube-forming
      polychaetes (Sabellariidae, Cirratulidae and Serpulidae), including descriptions
      of two new species of Selenidium.
AB  - Selenidium is a genus of gregarine parasites that infect the intestines of marine
      invertebrates and have morphological, ecological, and motility traits inferred to
      reflect the early evolutionary history of apicomplexans. Because the overall
      diversity and phylogenetic position(s) of these species remain poorly understood,
      we performed a species discovery survey of Selenidium from tube-forming
      polychaetes. This survey uncovered five different morphotypes of trophozoites
      (feeding stages) living within the intestines of three different polychaete
      hosts. We acquired small subunit (SSU) rDNA sequences from single-cell
      (trophozoite) isolates, representing all five morphotypes that were also imaged
      with light and scanning electron microscopy. The combination of molecular,
      ecological, and morphological data provided evidence for four novel species of
      Selenidium, two of which were established in this study: Selenidium
      neosabellariae n. sp. and Selenidium sensimae n. sp. The trophozoites of these
      species differed from one another in the overall shape of the cell, the specific
      shape of the posterior end, the number and form of longitudinal striations, the
      presence/absence of transverse striations, and the position and shape of the
      nucleus. A fifth morphotype of Selenidium, isolated from the tube worm
      Dodecaceria concharum, was inferred to have been previously described as
      Selenidium cf. echinatum, based on general trophozoite morphology and host
      association. Phylogenetic analyses of the SSU rDNA sequences resulted in a robust
      clade of Selenidium species collected from tube-forming polychaetes, consisting
      of the two new species, the two additional morphotypes, S. cf. echinatum, and
      four previously described species (Selenidium serpulae, Selenidium boccardiellae,
      Selenidium idanthyrsae, and Selenidium cf. mesnili). Genetic distances between
      the SSU rDNA sequences in this clade distinguished closely related and potential
      cryptic species of Selenidium that were otherwise very similar in trophozoite
      morphology. 

PMID- 23879626
TI  - NH/PH isomerization and a Lewis pair for carbon dioxide capture.
AB  - Bis(di-i-propylphosphino)amine 1 reacts with B(C6F5)3 to form an adduct with
      concomitant N/P H-isomerization. This species reacts smoothly with carbon
      dioxide. An attempt to prepare an anionic derivative resulted in the formation of
      a novel heterocycle derived from the PNP ligand and B(C6F5)3. 

PMID- 23879625
TI  - Progressive improvement in wound healing with increased therapy in haemophilia B
      mice.
AB  - Previous work has shown that normalized haemostasis only at the time of an injury
      is not sufficient to promote optimal wound healing in haemophilia B (HB) mice.
      However, the duration of treatment required for optimal healing has not been
      established. The goal of these studies was to determine the effect of different
      durations of replacement or bypassing therapy [factor IX(FIX) or factor VIIa
      (FVIIa)] on wound healing parameters in a mouse model of HB. A dermal wound was
      placed on the back of HB mice. Animals were either untreated or pretreated and
      then subsequently treated for 3 days, 5 days, or 7 days with FIX or FVIIa. Wound
      area, time to wound healing, haematoma formation and iron deposition were
      measured. All treated animals showed shortened time to healing relative to
      untreated animals. Haematoma formation was prevented by treatment and bleeding
      into the wounds, measured by iron scores, was reduced by treatment. In addition,
      there was a progressive improvement in healing with 7 days of treatment more
      effective than 5 days which was more effective than 3 days. Replacement therapy
      with FIX had slightly shorter healing times than bypassing therapy with FVIIa. HB
      mice treated with FIX had slightly smaller wound area than untreated animals; by
      contrast, FVIIa-treated animals had much smaller wound areas that were close to
      the wound areas seen in wild-type animals. The data suggest that sustained
      therapy is required for normal wound healing.

PMID- 23879627
TI  - Rapid generation of stable cell lines expressing high levels of erythropoietin,
      factor VIII, and an antihuman CD20 antibody using lentiviral vectors.
AB  - Lentiviral vectors (LVs) are widely recognized as the most efficient method for
      the stable delivery of nucleic acid sequences into mammalian cells. Using
      erythropoietin (EPO), recombinant factor VIII (fVIII), and an anti-CD20 antibody
      as model proteins, we demonstrate advantages of LV-based gene delivery to achieve
      high production levels by transduced cells. Highly productive cell clones were
      able to incorporate up to 100 vector copies per cellular genome, without
      selection or gene amplification, and were isolated without extensive screening of
      a large number of clones. The LV transgenes were shown to be distributed
      throughout the genome, as visualized by fluorescent in situ hybridization. High
      expressing clones producing 100-200 pg/cell/day of EPO were isolated and
      characterized. EPO production was demonstrated for at least 51/2 months of
      continuous culture without selection, during which all the clones displayed high
      levels of glycosylation despite production levels at 10-20 g/liter. To
      demonstrate the utility of LV technology for multiple classes of proteins, cell
      lines producing fVIII and an anti-CD20 antibody were also developed. Cell clones
      demonstrating high levels of fVIII (100 clot units/ml and anti-CD20 antibody as
      high as 40-100 pg/cell/day) were isolated and characterized. LV-transduced cells
      and plasmid-transfected cells were compared for protein production per transgene
      copy. LV-transduced cells produced significantly higher levels of protein per
      copy of transgene than plasmid-transfected cells did. This study demonstrates the
      utility of LV technology for rapid generation of highly productive and stable
      cell lines over conventional plasmid transfection methods, significantly
      decreasing the time, cost, and risk of the manufacture of proteins and other
      complex biological molecules.

PMID- 23879628
TI  - Oesophageal hyperkeratosis: clinicopathological associations.
AB  - AIMS: Oesophageal hyperkeratosis is rarely described. In contrast to
      hyperkeratosis of orolaryngeal mucosa, where its risk factors and association
      with squamous neoplasia are well-studied, the prevalence and clinicopathological
      features of oesophageal hyperkeratosis are unknown. METHODS AND RESULTS: We
      reviewed prospectively 1845 oesophageal biopsies and found hyperkeratosis in 37
      (2.0%). Among 98 patients studied, hyperkeratosis occurred in two distinct
      settings: group 1 [within Barrett's oesophagus (BO)/adenocarcinoma, n = 61, 62%]
      and group 2 (outside BO/adenocarcinoma, n = 37, 38%). In contrast to group 1,
      hyperkeratosis in group 2 was more often multifocal (>3 foci in 51% versus 16%, P
      = 0.0001), involved mid-oesophagus (51% versus 2%, P < 0.0001), showed endoscopic
      leucoplakia (24% versus 3%, P = 0.003) and involved current/former alcohol users
      (51% versus 19%, P = 0.0012). Importantly, invasive squamous carcinoma and
      squamous dysplasia were seen only in group 2 (47% and 19% versus 0%, P < 0.0001).
      Further, 42% of group 2, but none of group 1, had benign or malignant squamous
      lesions of the oral cavity/larynx (P < 0.0001). CONCLUSION: Hyperkeratosis
      involves ~2% of oesophageal biopsies and can be divided into cases occurring
      within BO/adenocarcinoma and those occurring outside BO/adenocarcinoma. The
      former lack clinical significance, whereas the latter are associated frequently
      with oesophageal squamous neoplasia and squamous pathology of the head and neck
      region.

PMID- 23879629
TI  - Burkholderia BcpA mediates biofilm formation independently of interbacterial
      contact-dependent growth inhibition.
AB  - Contact-dependent growth inhibition (CDI) is a phenomenon in which Gram-negative
      bacteria use the toxic C-terminus of a large surface-exposed exoprotein to
      inhibit the growth of susceptible bacteria upon cell-cell contact. Little is
      known about when and where bacteria express the genes encoding CDI system
      proteins and how these systems contribute to the survival of bacteria in their
      natural niche. Here we establish that, in addition to mediating interbacterial
      competition, the Burkholderia thailandensis CDI system exoprotein BcpA is
      required for biofilm development. We also provide evidence that the catalytic
      activity of BcpA and extracellular DNA are required for the characteristic
      biofilm pillars to form. We show using a bcpA-gfp fusion that within the biofilm,
      expression of the CDI system-encoding genes is below the limit of detection for
      the majority of bacteria and only a subset of cells express the genes strongly at
      any given time. Analysis of a strain constitutively expressing the genes
      indicates that native expression is critical for biofilm architecture. Although
      CDI systems have so far only been demonstrated to be involved in interbacterial
      competition, constitutive production of the system's immunity protein in the
      entire bacterial population did not alter biofilm formation, indicating a CDI
      independent role for BcpA in this process. We propose, therefore, that bacteria
      may use CDI proteins in cooperative behaviours, like building biofilm
      communities, and in competitive behaviours that prevent non-self bacteria from
      entering the community.

PMID- 23879631
TI  - Quantified explosives transfer on surfaces for the evaluation of trace detection
      equipment.
AB  - Trace explosive test surfaces are often required for the evaluation of trace
      detection equipment to determine the equipment performance. Test surfaces of C-4,
      Detasheet, Semtex-H, TNT, and HMTD were prepared by transferring trace amount of
      explosive deposited on polytetrafluoroethylene (PTFE) transfer strips onto
      different surfaces (Kraft paper, hard plastic, woven fabric, and soft vinyl). The
      amount of explosive transferred was deduced from the amount of explosive
      remaining on the PTFE strips after transfer, as quantified by direct analysis
      using tandem mass spectrometry with thermal desorption. From the data set of over
      2000 transfers, we experienced lower transfer efficiency for Semtex-H and
      Detasheet, and for soft vinyl and hard plastic. However, the rapid quantification
      mass spectrometric method allowed the transfer efficiency to be determined for
      all test surfaces used in an evaluation of trace explosive detectors, thereby
      permitting only the test surfaces with desired transfer to be accepted for the
      assessment. 

PMID- 23879630
TI  - Construction of gene clusters resembling genetic causal mechanisms for common
      complex disease with an application to young-onset hypertension.
AB  - BACKGROUND: Lack of power and reproducibility are caveats of genetic association
      studies of common complex diseases. Indeed, the heterogeneity of disease etiology
      demands that causal models consider the simultaneous involvement of multiple
      genes. Rothman's sufficient-cause model, which is well known in epidemiology,
      provides a framework for such a concept. In the present work, we developed a
      three-stage algorithm to construct gene clusters resembling Rothman's causal
      model for a complex disease, starting from finding influential gene pairs
      followed by grouping homogeneous pairs. RESULTS: The algorithm was trained and
      tested on 2,772 hypertensives and 6,515 normotensives extracted from four large
      Caucasian and Taiwanese databases. The constructed clusters, each featured by a
      major gene interacting with many other genes and identified a distinct group of
      patients, reproduced in both ethnic populations and across three genotyping
      platforms. We present the 14 largest gene clusters which were capable of
      identifying 19.3% of hypertensives in all the datasets and 41.8% if one dataset
      was excluded for lack of phenotype information. Although a few normotensives were
      also identified by the gene clusters, they usually carried less risky combinatory
      genotypes (insufficient causes) than the hypertensive counterparts. After
      establishing a cut-off percentage for risky combinatory genotypes in each gene
      cluster, the 14 gene clusters achieved a classification accuracy of 82.8% for all
      datasets and 98.9% if the information-short dataset was excluded. Furthermore,
      not only 10 of the 14 major genes but also many other contributing genes in the
      clusters are associated with either hypertension or hypertension-related diseases
      or functions. CONCLUSIONS: We have shown with the constructed gene clusters that
      a multi-causal pie-multi-component approach can indeed improve the
      reproducibility of genetic markers for complex disease. In addition, our novel
      findings including a major gene in each cluster and sufficient risky genotypes in
      a cluster for disease onset (which coincides with Rothman's sufficient cause
      theory) may not only provide a new research direction for complex diseases but
      also help to reveal the disease etiology.

PMID- 23879632
TI  - Understanding the -C-X1-X2-C- motif in the active site of the thioredoxin
      superfamily: E. coli DsbA and its mutants as a model system.
AB  - E. coli DsbA is an intensively studied enzyme of the thioredoxin superfamily of
      thiol-disulfide oxidoreductases. DsbA catalyzes the disulfide bond formation and
      folding of proteins in the bacterial periplasm. DsbA and its mutants have
      highlighted the strong and puzzling influence of the -C-X1-X2-C- active site
      variants, found across the thioredoxin superfamily, on the ionization and redox
      properties of this site. However, the interpretation of these observations
      remains wanting, largely due to a dearth of structural information. Here,
      molecular dynamics simulations are used to provide extensive information on the
      structure and dynamics of reduced -C30-X31-X32-C33- motifs in wild type DsbA and
      13 of its mutants. These simulations are combined with calculations of the pK of
      H32 and of the very low pK of the catalytic cysteine C30. In wild type DsbA, the
      titrations of C30 and H32 are shown to be coupled; the protonation states and
      dynamics of H32 are examined. The thiolate of C30 is stabilized by hydrogen bonds
      with the protein. Modulation of these hydrogen bonds by alteration of residue X32
      has the greatest impact on the pK of C30, which rationalizes its higher pK in
      thioredoxin and tryparedoxin. Because of structural constrains, residue X31 has
      only an indirect and weak influence on the pK of C30. The dynamics of C30 is
      clearly related to its stabilizing interactions and pK value. Although relatively
      small differences between pKs were not reproduced in the calculations, the major
      trends are explained, adding new insights to our understanding of enzymes in this
      family. 

PMID- 23879633
TI  - The influence of lithium cations on dynamics and structure of room temperature
      ionic liquids.
AB  - The orientational relaxation dynamics of perylene in the room temperature ionic
      liquid (RTIL) 1-butyl-3-methylimidazolium bis(trifluoromethyl)sulfonyl imide were
      studied as a function of lithium ion concentration. Perylene is nonpolar and
      locates in the alkyl regions of the RTIL. The lithium cation was added as lithium
      bis(trifluoromethyl)sulfonyl imide, so the addition of Li(+) did not change the
      anion. The Li(+) concentration ranged from 0 to 0.4 mol fraction. The dynamics
      were measured by observing the fluorescence anisotropy decay using time
      correlated single photon counting. The anisotropy experiments and viscosity
      measurements were performed as a function of temperature for each Li(+)
      concentration sample. Because perylene has high symmetry, it was possible to
      independently determine the in-plane and out-of-plane diffusion constants and
      friction coefficients. With increasing concentration of lithium salt the
      viscosity increases and both the in-plane and out-of-plane orientational
      relaxations of perylene become slower. However, the corresponding molecular
      friction coefficients decreased, with the in-plane coefficient decreasing to a
      greater extent than the out-of-plane coefficient. The decrease in the friction
      coefficients demonstrates that lithium ions, which are located in the ionic
      regions of the RTILs, change the structure of the alkyl regions of the RTIL. 

PMID- 23879634
TI  - Frailty Index in Europeans: association with determinants of health.
AB  - AIM: The Frailty Index (FI) summarizes differences in health status within
      individuals, and the determinants of health drive that variability. The aim of
      the present study was to investigate the influence of education, income, smoking,
      alcohol intake and parental longevity on the FI variability in subjects of the
      same chronological age group. METHODS: Analyses were based on a 40-item FI based
      on the first wave of the Survey of Health, Aging and Retirement in Europe (SHARE,
      http://www.share-project.org/), including 29 905 participants aged >=50 years
      from 12 countries. For each sex, the sample was divided into age categories (50s,
      60s, 70s, 80s and >=90), and FI quartiles within age categories were calculated.
      Multivariate ordinal regressions were computed to assess the relative
      contribution of the health determinants on the FI quartiles in each age group.
      RESULTS: In women, the most significant multivariate predictors were years of
      education (odds ratios [OR] around 0.9), and difficulties making ends meet (OR
      between 1.8 and 2.1). In men, the most significant multivariate predictors were
      years of education (OR around 0.9), difficulties making ends meet (OR between 1.6
      and 2.1), mother's age at death (OR under 1), and father's age at death (OR under
      1). CONCLUSIONS: Consistently with the literature, education and income
      explained, in both sexes, cross-sectional variability in FI in subjects of the
      same chronological age group. The influence of parental longevity seemed to be
      greater in men, which mirrors previous studies showing that genetic factors might
      have a higher impact on longevity in men.

PMID- 23879635
TI  - ApoE enhances nanodisk-mediated curcumin delivery to glioblastoma multiforme
      cells.
AB  - AIM: To evaluate the effect of incorporating the polyphenol, curcumin, into
      nanodisk (ND) particles on its biological activity. MATERIALS & METHODS: Curcumin
      NDs formulated with different scaffold proteins were incubated with cultured
      glioblastoma multiforme cells. RESULTS: When ApoE was employed as the ND scaffold
      protein, enhanced curcumin uptake was observed. Furthermore, ApoE curcumin-NDs
      induced greater cell death than either free curcumin or ApoAI curcumin-NDs. A
      total of 1 h after exposure of glioblastoma multiforme cells to ApoE curcumin
      NDs, significant curcumin uptake was detected while ApoE was localized at the
      cell surface. After 2 h, a portion of the curcumin had migrated to the nucleus,
      giving rise to enhanced fluorescence intensity in discrete intranuclear sites.
      CONCLUSION: ApoE-mediated interaction of curcumin-NDs with glioblastoma
      multiforme cells leads to enhanced curcumin uptake and increased biological
      activity.

PMID- 23879636
TI  - Dissipation of pirimiphos-methyl during wheat fermentation by Lactobacillus
      plantarum.
AB  - In this study, the dissipation of pirimiphos-methyl during wheat fermentation by
      Lactobacillus plantarum was investigated. Sample preparation for GC/MS detection
      of pirimiphos-methyl residues from fermented wheat substrate was carried out by
      two steps: extraction with 25 mL of methanol : acetone = 1 : 1 solvent mix for 30
      min, followed by clean-up procedure through a glass column with florisil coupled
      with elution by 25 mL of ethyl acetate : acetone = 4 : 1. To obtain the highest
      pesticide degradation level, the fermentation conditions were optimized according
      to response surface methodology. Our results showed that L. plantarum was able to
      reduce the level of pirimiphos-methyl in wheat. Although pirimiphos-methyl was
      partially labile during sterilization prior inoculation (~37-50%), and there was
      also spontaneous chemical degradation of pesticide (~6-11%), overall L. plantarum
      enhanced degradation from 15 to 34%, that is, to nearly 81%. Additionally, the
      effect of pirimiphos-methyl on the lactobacilli growth, and efficiency of
      fermentation, was studied where pirimiphos-methyl inhibit the growth of bacteria
      in concentrations higher than 5 mg kg(-1), while the presence of pirimiphos
      methyl did not overall affect the lactic acid fermentation.

PMID- 23879638
TI  - L-diphenylalanine microtubes as a potential drug-delivery system:
      characterization, release kinetics, and cytotoxicity.
AB  - Microtubes obtained from the self-assembly of L-diphenylalanine (FF-MTs) were
      evaluated as potential vehicles for drug delivery. The biological marker
      Rhodamine B (RhB) was chosen as a model drug and conjugated to the peptide arrays
      during self-organization in the liquid phase. Microscopy and X-ray studies were
      performed to provide morphological and structural information. The data revealed
      that the cargo was distributed either in small aggregates at the hydrophobic
      surface of the FF-MTs or homogeneously embedded in the structure, presumably
      anchored at polar sites in the matrix. Raman spectroscopy revealed notable shifts
      of the characteristic RhB resonance peaks, demonstrating the successful
      conjugation of the fluorophore and peptide assemblies. In vitro assays were
      conducted in erythrocytes and fibroblast cells. Interestingly, FF-MTs were found
      to modulate the release of the load. The release of RhB from the FF-MTs followed
      first-order kinetics with a steady-state profile, demonstrating the potential of
      these carriers to deliver drugs at constant rates in the body. Cytotoxicity
      investigations revealed high cell viability up to concentrations of 5 mg mL(-1),
      demonstrating the low toxicity of the FF-MTs.

PMID- 23879637
TI  - Commonalities and differences in infant feeding attitudes and practices in the
      context of HIV in sub-Saharan Africa: a metasynthesis.
AB  - Exclusive breastfeeding (EBF) has been identified as a key intervention to
      promote infant health and to reduce the vertical transmission of HIV. Despite
      this knowledge and increased resources to promote EBF, the practice in sub
      Saharan Africa (SSA) remains low among HIV+ women. Although a number of
      qualitative studies have been conducted throughout SSA, the influences on and
      consequences of infant feeding choices of HIV+ mothers' findings have not been
      regarded systematically. Therefore, our objective was to identify overarching
      themes, commonalities, and differences in infant feeding choices among
      qualitative studies with HIV+ mothers in SSA. Sixteen qualitative studies of
      infant feeding practices in the context of HIV were identified. Noblit and Hare's
      seven-step metasynthesis methodology was used to analyze the experiences of HIV+
      women and those who provide infant feeding services/counseling. Data were
      available from approximately 920 participants (i.e., 750 HIV+ mothers, 109 health
      care providers, and 62 family members) across 13 SSA countries from 2000 to 2011.
      From these data, five themes emerged within which 3-4 overarching key metaphors
      were identified. The consistency of key metaphors across a variety of geographic,
      economic, and cultural settings suggest the importance of approaching infant
      feeding holistically, within the context of maternal knowledge, health-care
      support, family resources, and cultural expectations. EBF campaigns in SSA are
      more likely to successfully support optimal health for infants and a safe
      supportive environment for their mothers when the impact of infant feeding
      decisions are evaluated across these themes. 

PMID- 23879639
TI  - A novel lobule rotation flap for the reconstruction of middle third auricular
      defects.
AB  - BACKGROUND: There are numerous techniques for the reconstruction of cutaneous
      defects of the pinna. Many of these distort the auricle, and several are
      challenging and time-consuming to perform. METHODS: An illustrative case is
      presented to demonstrate a novel lobule rotational flap, which can be used to
      cover cutaneous defects of the middle third of the pinna. RESULTS: Postoperative
      photography illustrates that this simple one-stage technique causes minimal
      anatomical distortion and allows the final scar to be concealed within the inner
      helical rim. CONCLUSIONS: Small local flaps can be raised from the lobule to
      cover challenging defects of the middle third of the pinna. In selected patients,
      with abundant lobular tissue, this technique can be as effective as more complex
      reconstructive options.

PMID- 23879640
TI  - Sandwich-Stacked SnO2/Cu Hybrid Nanosheets as Multichannel Anodes for Lithium Ion
      Batteries.
AB  - We have introduced a facile strategy to fabricate sandwich-stacked SnO2/Cu hybrid
      nanosheets as multichannel anodes for lithium-ion batteries applying rolled-up
      nanotechnology with the use of carbon black as intersheet spacer. By employing a
      direct self-rolling and compressing approach, a much higher effective volume
      efficiency is achieved as compared to rolled-up hollow tubes. Benefiting from the
      nanogaps formed between each neighboring sheet, electron transport and ion
      diffusion are facilitated and SnO2/Cu nanosheet overlapping is prevented. As a
      result, the sandwich-stacked SnO2/Cu hybrid nanosheets exhibit a high reversible
      capacity of 764 mAh g(-1) at 100 mA g(-1) and a stable cycling performance of
      ~75% capacity retention at 200 mA g(-1) after 150 cycles, as well as a superior
      rate capability of ~470 mAh g(-1) at 1 A g(-1). This synthesis approach presents
      a promising route to design multichannel anodes for high performance Li-ion
      batteries.

PMID- 23879642
TI  - Dermatology missed appointments: an analysis of outpatient non-attendance in a
      general hospital's population.
AB  - BACKGROUND: Non-attendance of scheduled appointments is a serious issue in
      dermatology hospital practice with implications in patient care. Herein we aim to
      characterize the population of non-attendees of dermatology appointments at a
      general hospital. MATERIAL AND METHODS: A prospective study was carried out of
      the reschedule requests received from January to December 2009 at a dermatology
      outpatient department of a general hospital. Variables such as gender, age, type
      of consultation, justification for non-attendance, timing between missed
      appointments and the reschedule request as well as rates of other missed
      appointments were analyzed. RESULTS: Throughout the study period, 265 patients
      filed a written request to reschedule a missed appointment, of whom 165 were
      female and 100 were male. The age distribution displayed two peaks, one in the
      second and the other in the sixth decade. Regarding the type of consultation,
      there was a clear predominance of missed follow-up consultations. Confusion and
      illness were the most frequent excuses for non-attendance. CONCLUSION: We propose
      to identify patients at risk of missed appointments and suggest interventions to
      overcome this pitfall and improve patient outcomes.

PMID- 23879643
TI  - Limitations of cadence-based walking for assessing bouts of moderate-to vigorous
      intensity physical activity under free-living conditions.
AB  - The purpose of the present investigation was to examine the relationship between
      the accumulation of 1000 steps in 10 minutes (1K) and 3000 steps in 30 minutes
      (3K) with the amount and intensity of daily physical activity. Thirty-three
      adults (16 males and 17 females, 53 +/- 19 years) wore an accelerometer
      (Lifecorder) for seven consecutive days in order to determine the number of steps
      and the time spent in physical activity at light intensity (LPA), moderate
      intensity (MPA), vigorous intensity (VPA) and moderate to vigorous intensity
      (MVPA). Furthermore, based on the minute-by-minute stepping rate, the number,
      intensity and duration of walking bouts (1K and 3K) were evaluated. The daily
      number of steps, LPA, MPA and VPA were significantly higher on the days with 1K
      or 3K compared with that observed on the days without 1K or 3K (P <0.05). The
      duration of 1K was not found to be correlated with an MVPA >10 minutes. An MVPA
      >10 minutes was less than 2 min . day(-1) on the days with 1K or 3K. Therefore,
      it is doubtful that the concept of cadence is an alternative indicator for the
      commonly used definition of MVPA. It remains unclear whether participation in 1K
      and 3K guarantees that an individual will meet the current MVPA guidelines.

PMID- 23879641
TI  - Sphingosine-1-phosphate receptor 2.
AB  - Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid involved in cell
      proliferation, angiogenesis, inflammation and malignant transformation among
      other functions. S1P acts either directly on intracellular targets or activates G
      protein-coupled receptors, specifically five S1P receptors (S1PRs). The
      identified S1PRs differ in cellular and tissue distribution, and each is coupled
      to specific G proteins, which mediate unique functions. Here, we describe
      functional characteristics of all five receptors, emphasizing S1PR2, which is
      critical in the immune, nervous, metabolic, cardiovascular, musculoskeletal, and
      renal systems. This review also describes the role of this receptor in tumor
      growth and metastasis and suggests potential therapeutic avenues that exploit
      S1PR2. 

PMID- 23879644
TI  - Impact of geometric variations on delivered dose in highly focused single vocal
      cord IMRT.
AB  - PURPOSE: To investigate the robustness of single vocal cord intensity modulated
      radiation therapy (IMRT) treatment plans for set-up errors, respiration, and
      deformation. MATERIAL AND METHODS: Four-dimensional computed tomography (4D-CT)
      scans of 10 early glottic carcinoma patients, previously treated with
      conventional techniques, were used in this simulation study. For each patient a
      pre-treatment 4D-CT was used for IMRT planning, generating a reference dose
      distribution. Prescribed PTV dose was 66 Gy. The impact of systematic set-up
      errors was simulated by applying shifts of +/- 2 mm to the planning CT scans,
      followed by dose re-calculation with original beam segments, MUs, etc. Effects of
      respiration and deformation were determined utilizing extreme inhale and exhale
      CT scans, and repeat scans acquired after 22 Gy, 44 Gy, and 66 Gy, respectively.
      All doses were calculated using Monte Carlo dose simulations. RESULTS:
      Considering all investigated geometrical perturbations, reductions in the
      clinical target volume (CTV) V95%, D98%, D2%, and generalized equivalent uniform
      dose (gEUD) were limited to 1.2 +/- 2.2%, 2.4 +/- 2.9%, 0.2 +/- 1.8%, and 0.6 +/-
      1.1 Gy, respectively. The near minimum dose, D98%, was always higher than 89%,
      and gEUD always remained higher than 66 Gy. Planned contra-lateral (CL) vocal
      cord DMean, gEUD, and V40 Gy were 38.2 +/- 6.0 Gy, 43.4 +/- 5.6 Gy, and 42.7 +/-
      14.9%. With perturbations these values changed by -0.1 +/- 4.3 Gy, 0.1 +/- 4.0
      Gy, and -1.0 +/- 9.6%, respectively. CONCLUSIONS: On average, CTV dose reductions
      due to geometrical perturbations were very low, and sparing of the CL vocal cord
      was maintained. In a few observations (6 of 103 simulated situations), the near
      minimum CTV-dose was around 90%, requiring attention in deciding on a future
      clinical protocol.

PMID- 23879645
TI  - Variations in magnitude and directionality of respiratory target motion
      throughout full treatment courses of stereotactic body radiotherapy for tumors in
      the liver.
AB  - PURPOSE: To investigate the stability of target motion amplitude and motion
      directionality throughout full stereotactic body radiotherapy (SBRT) treatments
      of tumors in the liver. MATERIAL AND METHODS: Ten patients with gold markers
      implanted in the liver received 11 courses of 3-fraction SBRT on a conventional
      linear accelerator. A four-dimensional computed tomography (4DCT) scan was
      obtained for treatment planning. The time-resolved marker motion was determined
      throughout full treatment field delivery using the kV and MV imagers of the
      accelerator. The motion amplitude and motion directionality of all individual
      respiratory cycles were determined using principal component analysis (PCA). The
      variations in motion amplitude and directionality within the treatment courses
      and the difference from the motion in the 4DCT scan were determined. RESULTS: The
      patient mean (+/- 1 standard deviation) peak-to-peak 3D motion amplitude of
      individual respiratory cycles during a treatment course was 7.9 +/- 4.1 mm and
      its difference from the 4DCT scan was -0.8 +/- 2.5 mm (max, 6.6 mm). The mean
      standard deviation of 3D respiratory cycle amplitude within a treatment course
      was 2.0 +/- 1.6 mm. The motion directionality of individual respiratory cycles on
      average deviated 4.6 +/- 1.6 degrees  from the treatment course mean
      directionality. The treatment course mean motion directionality on average
      deviated 7.6 +/- 6.5 degrees  from the directionality in the 4DCT scan. A single
      patient-specific oblique direction in space explained 97.7 +/- 1.7% and 88.3 +/-
      10.1% of all positional variance (motion) throughout the treatment courses,
      excluding and including baseline shifts between treatment fields, respectively.
      CONCLUSION: Due to variable breathing amplitudes a single 4DCT scan was not
      always representative of the mean motion amplitude during treatment. However, the
      motion was highly directional with a fairly stable direction throughout
      treatment, indicating a potential for more optimal individualized motion margins
      aligned to the preferred direction of motion.

PMID- 23879646
TI  - Functional imaging to monitor vascular and metabolic response in canine head and
      neck tumors during fractionated radiotherapy.
AB  - Radiotherapy causes alterations in tumor biology, and non-invasive early
      assessment of such alterations may become useful for identifying treatment
      resistant disease. The purpose of the current work is to assess changes in
      vascular and metabolic features derived from functional imaging of canine head
      and neck tumors during fractionated radiotherapy. Material and methods. Three
      dogs with spontaneous head and neck tumors received intensity-modulated
      radiotherapy (IMRT). Contrast-enhanced cone beam computed tomography (CE-CBCT) at
      the treatment unit was performed at five treatment fractions. Dynamic (18)FDG-PET
      (D-PET) was performed prior to the start of radiotherapy, at mid-treatment and at
      3-12 weeks after the completion of treatment. Tumor contrast enhancement in the
      CE-CBCT images was used as a surrogate for tumor vasculature. Vascular and
      metabolic tumor parameters were further obtained from the D-PET images. Changes
      in these tumor parameters were assessed, with emphasis on intra-tumoral
      distributions. Results. For all three patients, metabolic imaging parameters
      obtained from D-PET decreased from the pre- to the inter-therapy session.
      Correspondingly, for two of three patients, vascular imaging parameters obtained
      from both CE-CBCT and D-PET increased. Only one of the tumors showed a clear
      metabolic response after therapy. No systematic changes in the intra-tumor
      heterogeneity in the imaging parameters were found. Conclusion. Changes in
      vascular and metabolic parameters could be detected by the current functional
      imaging methods. Vascular tumor features from CE-CBCT and D-PET corresponded
      well. CE-CBCT is a potential method for easy response assessment when the patient
      is at the treatment unit.

PMID- 23879647
TI  - Real-time 2D/3D registration using kV-MV image pairs for tumor motion tracking in
      image guided radiotherapy.
AB  - Intra-fractional respiratory motion during radiotherapy leads to a larger
      planning target volume (PTV). Real-time tumor motion tracking by two-dimensional
      (2D)/3D registration using on-board kilo-voltage (kV) imaging can allow for a
      reduction of the PTV though motion along the imaging beam axis cannot be resolved
      using only one projection image. We present a retrospective patient study
      investigating the impact of paired portal mega-voltage (MV) and kV images on
      registration accuracy. Material and methods. We used data from 10 patients
      suffering from non-small cell lung cancer (NSCLC) undergoing stereotactic body
      radiation therapy (SBRT) lung treatment. For each patient we acquired a planning
      computed tomography (CT) and sequences of kV and MV images during treatment. We
      compared the accuracy of motion tracking in six degrees-of-freedom (DOF) using
      the anterior-posterior (AP) kV sequence or the sequence of kV-MV image pairs.
      Results. Motion along cranial-caudal direction could accurately be extracted when
      using only the kV sequence but in AP direction we obtained large errors. When
      using kV-MV pairs, the average error was reduced from 2.9 mm to 1.5 mm and the
      motion along AP was successfully extracted. Mean registration time was 188 ms.
      Conclusion. Our evaluation shows that using kV-MV image pairs leads to improved
      motion extraction in six DOF and is suitable for real-time tumor motion tracking
      with a conventional LINAC.

PMID- 23879648
TI  - Patient-specific scatter correction in clinical cone beam computed tomography
      imaging made possible by the combination of Monte Carlo simulations and a ray
      tracing algorithm.
AB  - PURPOSE: Cone beam computed tomography (CBCT) image quality is limited by
      scattered photons. Monte Carlo (MC) simulations provide the ability of predicting
      the patient-specific scatter contamination in clinical CBCT imaging. Lengthy
      simulations prevent MC-based scatter correction from being fully implemented in a
      clinical setting. This study investigates the combination of using fast MC
      simulations to predict scatter distributions with a ray tracing algorithm to
      allow calibration between simulated and clinical CBCT images. MATERIAL AND
      METHODS: An EGSnrc-based user code (egs_cbct), was used to perform MC simulations
      of an Elekta XVI CBCT imaging system. A 60 keV x-ray source was used, and air
      kerma scored at the detector plane. Several variance reduction techniques (VRTs)
      were used to increase the scatter calculation efficiency. Three patient phantoms
      based on CT scans were simulated, namely a brain, a thorax and a pelvis scan. A
      ray tracing algorithm was used to calculate the detector signal due to primary
      photons. A total of 288 projections were simulated, one for each thread on the
      computer cluster used for the investigation. RESULTS: Scatter distributions for
      the brain, thorax and pelvis scan were simulated within 2% statistical
      uncertainty in two hours per scan. Within the same time, the ray tracing
      algorithm provided the primary signal for each of the projections. Thus, all the
      data needed for MC-based scatter correction in clinical CBCT imaging was obtained
      within two hours per patient, using a full simulation of the clinical CBCT
      geometry. CONCLUSIONS: This study shows that use of MC-based scatter corrections
      in CBCT imaging has a great potential to improve CBCT image quality. By use of
      powerful VRTs to predict scatter distributions and a ray tracing algorithm to
      calculate the primary signal, it is possible to obtain the necessary data for
      patient specific MC scatter correction within two hours per patient.

PMID- 23879649
TI  - Dose/volume-based evaluation of the accuracy of deformable image registration for
      the rectum and bladder.
AB  - BACKGROUND AND PURPOSE: Deformable image registration (DIR) is a key component of
      image-guided and adaptive strategies in radiotherapy. DIR based on image
      intensities alone is promising for online applications, but is challenged in
      regions with low intensity gradients. In this study we have investigated the
      performance of intensity- based DIR applied to contour propagation of the rectum
      and bladder, focusing on the consequences in terms of dose/volume parameters.
      MATERIAL AND METHODS: The rectum and bladder volumes were delineated in the
      planning computed tomography (pCT) scan and in 8-9 repeat CTs (Vmanual) for nine
      prostate cancer patients. The volumes from the pCT were propagated onto the
      repeat CTs using intensity-based DIR (Vprop). Dose/volume parameters for Vmanual
      and Vprop were derived by dose re-calculations following rigid registration on
      prostate fiducials. Linear regression was used to identify qualitative and
      quantitative volumetric measures of the DIR performance being associated with the
      differences in dose/volume parameters. RESULTS: The median differences in
      dose/volume parameters assessed for Vprop and Vmanual were modest, but individual
      differences ~7 Gy were seen. The observed differences in dose/volume parameters
      showed strong correlations to the measures of the DIR performance as well as with
      the volume variations, most pronounced for the rectum (R(2) = 0.63-0.85; p <=
      0.05). CONCLUSION: Limitations in the intensity-based DIR algorithm resulted in
      large individual differences in dose/volume parameters between propagated and
      manually segmented volumes, which were correlated with volumetric measures of the
      DIR performance.

PMID- 23879650
TI  - Identification and characterization of nodal metastases in prostate cancer
      patients at high risk for lymph node involvement.
AB  - AIM: To investigate whether blood-based markers could be used to identify
      prostate cancer (PCa) patients harboring lymph node (LN) metastases. In addition,
      E-cadherin expression was studied within the concept of epithelial mesenchymal
      plasticity. MATERIAL AND METHODS: Seventy-five patients with clinically localized
      PCa who underwent a superextended lymphadenectomy followed by radical
      prostatectomy (RP) were included in this study. Preoperative plasma/serum levels
      of endoglin, transforming growth factor-beta1 (TGF-beta1), osteopontin, vascular
      endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), and
      E-cadherin were measured using commercially available enzyme immunoassays in
      47/75 patients and correlated with clinicopathological parameters. E-cadherin
      expression in the diagnostic biopsies (n = 63), RP specimens (n = 75) and LN
      metastases (n = 106) was examined by immunohistochemical analysis. RESULTS:
      Occult LN metastases were present in almost half of the patients (37/75), with a
      total of 106 affected LN. Preoperative levels of endoglin, TGF-beta1,
      osteopontin, VEGF, VCAM-1 nor E-cadherin were significantly associated with LN
      status. Only a positive correlation between plasma endoglin and serum prostate
      specific antigen was found (Spearman's r = 0.44; p = 0.002). The majority of
      biopsies (91.9%) and RP specimens (79.7%) showed strong E-cadherin expression,
      while in the LN this was found to be much weaker (28.9%). While the staining
      pattern in the isolated tumor cells (ITC) and micrometastases was mainly
      homogenous, the macrometastases showed a much more heterogeneous pattern (chi2, p
      < 0.0001). CONCLUSION: In this study, none of the blood-based markers tested
      could be used for nodal staging in PCa, nor could E-cadherin expression in the
      tissue. However, the difference in E-cadherin expression pattern between the
      ITC/micrometastases and the macrometastases may point to another biological
      behavior. The specific staining pattern seen in the macrometastases could
      indicate an ongoing mesenchymal epithelial transition, presumed to be a mechanism
      for metastatic colonization. As the latter is the rate-limiting step in the
      metastatic process, evaluation of the E-cadherin expression pattern could have
      potential therapeutic implications.

PMID- 23879651
TI  - A strategy for multimodal deformable image registration to integrate PET/MR into
      radiotherapy treatment planning.
AB  - BACKGROUND: Combined positron emission tomography (PET)/magnetic resonance
      imaging (MRI) is highly promising for biologically individualized radiotherapy
      (RT). Hence, the purpose of this work was to develop an accurate and robust
      registration strategy to integrate combined PET/MR data into RT treatment
      planning. Material and methods. Eight patient datasets consisting of an FDG
      PET/computed tomography (CT) and a subsequently acquired PET/MR of the head and
      neck (HN) region were available. Registration strategies were developed based on
      CT and MR data only, whereas the PET components were fused with the resulting
      deformation field. Following a rigid registration, deformable registration was
      performed with a transform parametrized by B-splines. Three different
      optimization metrics were investigated: global mutual information (GMI), GMI
      combined with a bending energy penalty (BEP) for regularization (GMI+ BEP) and
      localized mutual information with BEP (LMI+ BEP). Different quantitative
      registration quality measures were developed, including volumetric overlap and
      mean distance measures for structures segmented on CT and MR as well as
      anatomical landmark distances. Moreover, the local registration quality in the
      tumor region was assessed by the normalized cross correlation (NCC) of the two
      PET datasets. RESULTS: LMI+ BEP yielded the most robust and accurate registration
      results. For GMI, GMI+ BEP and LMI+ BEP, mean landmark distances (standard
      deviations) were 23.9 mm (15.5 mm), 4.8 mm (4.0 mm) and 3.0 mm (1.0 mm), and mean
      NCC values (standard deviations) were 0.29 (0.29), 0.84 (0.14) and 0.88 (0.06),
      respectively. CONCLUSION: Accurate and robust multimodal deformable image
      registration of CT and MR in the HN region can be performed using a B-spline
      parametrized transform and LMI+ BEP as optimization metric. With this strategy,
      biologically individualized RT based on combined PET/MRI in terms of dose
      painting is possible.

PMID- 23879652
TI  - Massive bone marrow involvement in an end stage renal failure case with
      erythropoietin-resistant anemia and primary hyperoxaluria.
AB  - Primary hyperoxaluria is a rare autosomal recessive disorder. Type 1 PH is the
      most common form and develops due to a defect in a liver specific enzyme the
      alanine aminotransferase enzyme. As a result of the enzyme deficiency, there is
      an overproduction of oxalate and excessive urinary excretion. Recurrent
      urolithiasis and nephrocalcinosis are the most important findings of the disorder
      and often at the beginning end-stage renal disease develops. This report presents
      a case backed up by literature of a patient with end stage renal failure and
      erythropoietin-resistant anaemia whose bone marrow biopsy showed crystal
      deposition which received delayed diagnosis of oxalosis.

PMID- 23879653
TI  - Vinylogy in orthoester hydrolysis: total syntheses of cyclophellitol,
      valienamine, gabosine K, valienone, gabosine G, 1-epi-streptol, streptol, and
      uvamalol A.
AB  - C7-cyclitols represent an important category of natural products possessing a
      broad spectrum of biological activities. As each member of these compounds is
      structurally unique, the usual practice is to synthesize them individually from
      appropriate polyhydroxylated chiral pools. We have observed an unusual vinylogy
      in acid mediated hydrolysis of enol ethers of myo-inositol 1,3,5-orthoesters
      giving a synthetically versatile polyhydroxylated cyclohexenal intermediate. We
      have exploited this unprecedented reaction for developing a general strategy for
      the rapid and efficient syntheses of several structurally diverse natural
      products of C7-cyclitol family. We have made an appropriately protected advanced
      intermediate 25 in five steps from the cheap and commercially available myo
      inositol, and this common intermediate has been used to synthesize eight natural
      products in racemic form. We could synthesize (+/-)-cyclophellitol in seven
      steps, (+/-)-valienamine in five steps, (+/-)-gabosine I in five steps, (+/-)
      gabosine G in six steps, (+/-)-gabosine K in three steps, (+/-)-streptol in six
      steps, (+/-)-1-epi-streptol in two steps, and (+/-)-uvamalol A in five steps from
      this intermediate. 

PMID- 23879654
TI  - Comparative characterization of stromal vascular cells derived from three types
      of vascular wall and adipose tissue.
AB  - Multipotent stem/progenitor cells localize perivascularly in many organs and
      vessel walls. These tissue-resident stem/progenitor cells differentiate into
      vascular endothelial cells, pericytes, and other mesenchymal lineages, and
      participate in physiological maintenance and repair of vasculatures. In this
      study, we characterized stromal vascular cells obtained through the explant
      culture method from three different vessel walls in humans: arterial wall (ART;
      >500 MUm in diameter), venous wall (VN; >500 MUm in diameter), and small vessels
      in adipose tissue (SV; arterioles and venules, <100 MUm in diameter). These were
      examined for functionality and compared with adipose-derived stem/stromal cells
      (ASCs). All stromal vascular cells of different origins presented fibroblast-like
      morphology and we could not visually discriminate one population from another.
      Flow cytometry showed that the cultured population heterogeneously expressed a
      variety of surface antigens associated with stem/progenitor cells, but CD105 was
      expressed by most cells in all groups, suggesting that the cells generally shared
      the characteristics of mesenchymal stem cells. Our histological and flow
      cytometric data suggested that the main population of vessel wall-derived stromal
      vascular cells were CD34(+)/CD31(-) and came from the tunica adventitia and
      areola tissue surrounding the adventitia. CD271 (p75NTR) was expressed by the
      vasa vasorum in the VN adventitia and by a limited population in the adventitia
      of SV. All three populations differentiated into multiple lineages as did ASCs.
      ART cells induced the largest quantity of calcium formation in the osteogenic
      medium, whereas ASCs showed the greatest adipogenic differentiation. SV and VN
      stromal cells had greater potency for network formation than did ART stromal
      cells. In conclusion, the three stromal vascular populations exhibited
      differential functional properties. Our results have clinical implications for
      vascular diseases such as arterial wall calcification and possible applications
      to regenerative therapies involving each vessel wall-resident stromal population.

PMID- 23879656
TI  - Epidemiology and variables involved in dental abscess: survey of dental emergency
      unit in Trieste.
AB  - OBJECTIVES: The objective of this epidemiologic study was to estimate the healing
      time of acute dental abscesses and to evaluate the main variables involved in the
      healing process itself. SUBJECTS AND METHODS: Among a sample of over 24 000
      patients visited at the emergency dental unit, 688 subjects were diagnosed with
      dental abscess and enrolled in the study. Case histories of all patients were
      collected to investigate the clinical course and healing time of dental abscess
      according to anamnestic and diagnostic data and therapeutic management. A
      multiple logistic regression model was performed to evaluate the association of
      each variable with the healing time required for dental abscess. RESULTS:
      Variables associated with increased healing time were spring seasonality at
      admission, pyretic state, trismus, involvement of multiple anatomic spaces, and
      spontaneous drainage. Moreover, administration of some, but not all, classes of
      antibiotics was also associated with an increased healing time. CONCLUSIONS: The
      knowledge of variables involved in healing time for dental abscess is crucial in
      the optimization of managing such infections in terms of cost-benefit ratio. This
      would represent a valuable way to ensure a shortened and more effective healing.

PMID- 23879657
TI  - Ribosomal PCR and DNA sequencing for detection and identification of bacteria:
      experience from 6 years of routine analyses of patient samples.
AB  - The use of broad range PCR and DNA sequencing of bacterial 16S ribosomal RNA
      genes for routine diagnostics of bacterial infections was evaluated. Here, the
      results from more than 2600 analyses during a 6-year period (2003-2009) are
      presented. Almost half of the samples were from joints and bones, and the second
      most frequent origin of samples was from the central nervous system. Overall, 26%
      of all samples were positive for bacterial DNA and bacterial identification was
      obtained in 80% of the PCR-positive samples by subsequent DNA sequencing.
      Ambiguous species identification was noticed among non-haemolytic streptococci,
      especially within the mitis group. The data show that ribosomal PCR with
      subsequent DNA sequencing of the PCR product is a most valuable supplement to
      culture for identifying bacterial agents of both acute and prolonged infections.
      However, some bacteria, including non-haemolytic streptococci, may not be
      precisely identified. 

PMID- 23879655
TI  - Alcohol consumption is associated with lower self-reported disease activity and
      better health-related quality of life in female rheumatoid arthritis patients in
      Sweden: data from BARFOT, a multicenter study on early RA.
AB  - BACKGROUND: Earlier studies have found a positive effect of alcohol consumption,
      with a reduced disease activity in rheumatoid arthritis (RA). The aim of this
      study was to assess alcohol consumption and its association with disease activity
      and health related quality of life (HRQL) in Swedish RA patients. METHODS:
      Between 1992 and 2005, 2,800 adult patients were included in the BARFOT study of
      early RA in Sweden. In 2010 a self-completion postal questionnaire was sent to
      all 2,102 prevalent patients in the BARFOT study enquiring about disease
      severity, HRQL, and lifestyle factors. Alcohol consumption was assessed using the
      validated AUDIT-C questionnaire. RESULTS: A total of 1,238 out of 1,460 patients
      answering the questionnaire had data on alcohol consumption: 11% were non
      drinkers, 67% had a non-hazardous drinking, and 21% were classified as hazardous
      drinkers. Women who drank alcohol reported lower disease activity and better
      HRQL, but there were no association between alcohol consumption and disease
      activity in men. For current smokers, alcohol use was only associated with fewer
      patient-reported swollen joints. The outcome was not affected by kind of alcohol
      consumed. CONCLUSIONS: There was an association between alcohol consumption and
      both lower self-reported disease activity and higher HRQL in female, but not in
      male, RA patients.

PMID- 23879658
TI  - Dy(III) single-ion magnet showing extreme sensitivity to (de)hydration.
AB  - A new mononuclear dysprosium(III)-cucurbit[6]uril complex has been synthesized
      and characterized structurally and magnetically. It exhibits single-ion magnet
      (SIM) behavior with two slow magnetic relaxation processes, which are very
      sensitive to the solvation degree of the sample. Depending on the amount and type
      of the solvent in the structure, it is possible to switch the slow magnetic
      relaxation of this compound between the temperature-independent and temperature
      dependent regimes. 

PMID- 23879660
TI  - Teaching multi-step requesting and social communication to two children with
      autism spectrum disorders with three AAC options.
AB  - The present study involved comparing the acquisition of multi-step requesting and
      social communication across three AAC options: manual signing (MS), picture
      exchange (PE), and speech-generating devices (SGDs). Preference for each option
      was also assessed. The participants were two children with autism spectrum
      disorders (ASD) who had previously been taught to use each option to request
      preferred items. Intervention was implemented in an alternating-treatments
      design. During baseline, participants demonstrated low levels of correct
      communicative responding. With intervention, both participants learned the target
      responses (two- and three-step requesting responses, greetings, answering
      questions, and social etiquette responses) to varying levels of proficiency with
      each communication option. One participant demonstrated a preference for using
      the SGD and the other preferred PE. The importance of examining preferences for
      using one AAC option over others is discussed.

PMID- 23879659
TI  - Reannotation and extended community resources for the genome of the non-seed
      plant Physcomitrella patens provide insights into the evolution of plant gene
      structures and functions.
AB  - BACKGROUND: The moss Physcomitrella patens as a model species provides an
      important reference for early-diverging lineages of plants and the release of the
      genome in 2008 opened the doors to genome-wide studies. The usability of a
      reference genome greatly depends on the quality of the annotation and the
      availability of centralized community resources. Therefore, in the light of
      accumulating evidence for missing genes, fragmentary gene structures, false
      annotations and a low rate of functional annotations on the original release, we
      decided to improve the moss genome annotation. RESULTS: Here, we report the
      complete moss genome re-annotation (designated V1.6) incorporating the increased
      transcript availability from a multitude of developmental stages and tissue
      types. We demonstrate the utility of the improved P. patens genome annotation for
      comparative genomics and new extensions to the cosmoss.org resource as a central
      repository for this plant "flagship" genome. The structural annotation of 32,275
      protein-coding genes results in 8387 additional loci including 1456 loci with
      known protein domains or homologs in Plantae. This is the first release to
      include information on transcript isoforms, suggesting alternative splicing
      events for at least 10.8% of the loci. Furthermore, this release now also
      provides information on non-protein-coding loci. Functional annotations were
      improved regarding quality and coverage, resulting in 58% annotated loci
      (previously: 41%) that comprise also 7200 additional loci with GO annotations.
      Access and manual curation of the functional and structural genome annotation is
      provided via the http://www.cosmoss.org model organism database. CONCLUSIONS:
      Comparative analysis of gene structure evolution along the green plant lineage
      provides novel insights, such as a comparatively high number of loci with 5'-UTR
      introns in the moss. Comparative analysis of functional annotations reveals
      expansions of moss house-keeping and metabolic genes and further possibly
      adaptive, lineage-specific expansions and gains including at least 13% orphan
      genes.

PMID- 23879661
TI  - Combining molecular data with classical morphology for uncultured phagotrophic
      euglenids (Excavata): a single-cell approach.
AB  - Phagotrophic euglenids are one of the most diverse and important forms of
      heterotrophic flagellates in sediment systems, and are key to understanding the
      evolution of photosynthetic euglenids and 'primary osmotrophs', yet relatively
      little is known about their biodiversity and phylogenetic relationships. A wealth
      of light microscopy-based information is available, but little progress has been
      made in associating this with molecular sequence data. We established a protocol
      to obtain light microscopy data and molecular data from single euglenid cells
      isolated from environmental samples. Individual cells from freshwater and marine
      benthic samples were isolated and rinsed by micropipetting, documented using high
      resolution photomicroscopy, then subjected to single-cell nested PCR using taxon
      specific primers in combination with universal eukaryotic primers, generating >
      75% or full-length SSU rDNA sequences. As a proof-of-principle eight individuals
      were characterised and subjected to phylogenetic analyses. Many of these cells
      were identified as Anisonema or Dinema, and grouped with existing sequences
      assigned to these taxa, and with a 'Peranema sp.' sequence that we could now
      clearly demonstrate was misidentified or misannotated. Another cell is Heteronema
      c.f. exaratum, the first 'skidding heteronemid' for which sequence data are
      available. This is not closely related to Heteronema scaphurum, and intriguingly,
      branches as the sister group to primary osmotrophs. A cell similar to Ploeotia
      vitrea (the type of this genus), shows no particular phylogenetic affinity to
      Ploeotia costata, the best studied Ploeotia species. Our experimental protocol
      provides a useful starting point for future analyses on euglenid biodiversity
      (including environmental sequence surveys), and their evolution and systematics. 

PMID- 23879663
TI  - Noise coefficients of backscattered electron detectors for low voltage scanning
      electron microscopy.
AB  - Noise coefficients of backscattered electron (BSE) detectors for low voltage
      scanning electron microscopy were studied theoretically and experimentally. The
      conversion method of BSE detection, the scintillation detector with an
      acceleration of BSE and detectors with electron multipliers were considered.
      Formulae for noise coefficients were derived and noise coefficients of detectors
      were computed for different values of gains of detectors' components. Theoretical
      predictions of noise coefficients were compared with experimental results. 

PMID- 23879662
TI  - An iterative consensus-building approach to revising a genetics/genomics
      competency framework for nurse education in the UK.
AB  - AIM: To report a review of a genetics education framework using a consensus
      approach to agree on a contemporary and comprehensive revised framework.
      BACKGROUND: Advances in genomic health care have been significant since the first
      genetics education framework for nurses was developed in 2003. These, coupled
      with developments in policy and international efforts to promote nursing
      competence in genetics, indicated that review was timely. DESIGN: A structured,
      iterative, primarily qualitative approach, based on a nominal group technique.
      METHOD: A meeting convened in 2010 involved stakeholders in UK nursing education,
      practice and management, including patient representatives (n = 30). A consensus
      approach was used to solicit participants' views on the individual/family needs
      identified from real-life stories of people affected by genetic conditions and
      the nurses' knowledge, skills and attitudes needed to meet those needs. Five
      groups considered the stories in iterative rounds, reviewing comments from
      previous groups. Omissions and deficiencies were identified by mapping resulting
      themes to the original framework. Anonymous voting captured views. Educators at a
      second meeting developed learning outcomes for the final framework. FINDINGS:
      Deficiencies in relation to Advocacy, Information management and Ongoing care
      were identified. All competencies of the original framework were revised, adding
      an eighth competency to make explicit the need for ongoing care of the
      individual/family. CONCLUSION: Modifications to the framework reflect
      individual/family needs and are relevant to the nursing role. The approach
      promoted engagement in a complex issue and provides a framework to guide nurse
      education in genetics/genomics; however, nursing leadership is crucial to
      successful implementation.

PMID- 23879664
TI  - Osteoinductive and Osteopromotive Variability among Different Demineralized Bone
      Allografts.
AB  - OBJECTIVE: The purpose of this investigation was to compare the osteoinductive
      and osteopromotive potential of two widely used demineralized freeze-dried bone
      allografts (DFDBA) (Osteotech(r) DFDBA and LifeNet(r) DFDBA). MATERIAL AND
      METHODS: Twenty-seven male Wistar rats (mean body weight 200 g) were treated with
      either DFDBA from Osteotech and LifeNet or control for femoral and intramuscular
      defects and assigned to histological analysis at 2, 4, and 8 weeks
      postimplantation. Hematoxylin and eosin (H&E), Safranin-O, tartrate-resistant
      acid phosphatase (TRAP), and osteopontin (OPN) staining were performed.
      Quantitative analysis of mineralized new bone to total volume (BV/TV) was
      assessed by micro-computed tomography. RESULTS: Both allografts demonstrated
      osteoinductive potential at 2 weeks as assessed by intramuscular bone formation.
      LifeNet DFDBA displayed continual new bone formation at 4 and 8 weeks, whereas
      Osteotech particles were fully resorbed by 4 weeks postimplantation. Femur
      defects demonstrated significantly greater BV/TV at 4 and 8 weeks with higher
      expression of OPN staining around LifeNet DFDBA particles. TRAP-positive cells
      were visible in and around both allograft materials. CONCLUSION: The results from
      the present study indicate that variability among allografts exists. In the
      present, LifeNet DFDBA supported more new bone formation. Further larger animal
      models or clinical trials are required to validate these findings.

PMID- 23879665
TI  - Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of
      Parkinson's disease.
AB  - AIMS: A dose-response meta-analysis was carried out between Parkinson's disease
      (PD) risk, and coffee, tea and caffeine consumption. METHODS: A comprehensive
      search was carried out to identify eligible studies. The fixed or random effect
      model was used based on heterogeneity test. The dose-response relationship was
      assessed by restricted cubic spline. RESULTS: A total of 13 articles involving
      901 764 participants for coffee, eight articles involving 344 895 participants
      for tea and seven articles involving 492 724 participants for caffeine were
      included. A non-linear relationship was found between coffee consumption and PD
      risk overall, and the strength of protection reached the maximum at approximately
      3 cups/day (smoking-adjusted relative risk: 0.72, 95% confidence interval 0.65
      0.81). A linear relationship was found between tea and caffeine consumption, and
      PD risk overall, and the smoking-adjusted risk of PD decreased by 26% and 17% for
      every two cups/day and 200 mg/day increments, respectively. The association of
      coffee and tea consumption with PD risk was stronger for men than that for women,
      and the association of caffeine consumption with PD risk was stronger for ever
      users of hormones than that for never users of hormones among postmenopausal
      women. The aforementioned associations were weaker for USA relative to Europe or
      Asia. CONCLUSIONS: A linear dose-relationship for decreased PD risk with tea and
      caffeine consumption was found, whereas the strength of protection reached a
      maximum at approximately 3 cups/day for coffee consumption overall. Further
      studies are required to confirm the findings.

PMID- 23879666
TI  - Photochemical reaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen) with
      basic amino acids and dipeptides.
AB  - Photoreaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KP) with basic
      amino acids (histidine, lysine, and arginine) and dipeptides (carnosine and
      anserine) including a histidine moiety in phosphate buffer solution (pH 7.4) has
      been investigated with transient absorption spectroscopy. With UV irradiation KP(
      ) gave rise to a carbanion through a decarboxylation reaction, and the carbanion
      easily abstracted a proton from the surrounding molecule to yield a 3
      ethylbenzophenone ketyl biradical (EBPH). The dipeptides as well as the basic
      amino acids were found to accelerate the proton transfer reaction whereas alanine
      and glycine had no effect on the reaction, revealing that these amino acids
      having a protonated side chain act as a proton donor. The formation quantum yield
      of EBPH was estimated to be fairly large by means of an actinometrical method
      with benzophenone, and the bimolecular reaction rate constant for the proton
      transfer between the carbanion and the protonated basic amino acids or the
      protonated dipeptides was successfully determined. It has become apparent that
      the bimolecular reaction rate constant for the proton transfer depended on the
      acid dissociation constant for the side chain of the amino acids for the first
      time. This reaction mechanism was interpreted by difference of the heat of
      reaction for each basic amino acid based on the thermodynamical consideration.
      These results strongly suggest that the side chain of the basic amino acid
      residue in protein should play an important role for photochemistry of KP in
      vivo. 

PMID- 23879667
TI  - Conclusive evidence of the reconstituted hexasome proven by native mass
      spectrometry.
AB  - It has been suggested that the hexasome, in which one of the H2A/H2B dimers is
      depleted from the canonical nucleosome core particle (NCP), is an essential
      intermediate during NCP assembly and disassembly, but little structural evidence
      of this exists. In this study, reconstituted products in a conventional NCP
      preparation were analyzed by native electrospray ionization mass spectrometry,
      and it was found that the hexasome, which migrated in a manner almost identical
      to that of the octasome NCP in native polyacrylamide gel electrophoresis, was
      produced simultaneously with the octasome NCP. This result might contribute to
      understanding the assembly and disassembly mechanism of NCPs. 

PMID- 23879668
TI  - The management of alcoholic hepatitis: a prospective comparison of scoring
      systems.
AB  - BACKGROUND: The assessment of alcoholic hepatitis remains controversial. Several
      scores have been developed or used for this purpose. AIM: To study the use of the
      Glasgow Alcoholic Hepatitis Score (GAHS), the Discriminant Function (DF), Model
      for End-Stage Liver Disease (MELD) and the ABIC (age, bilirubin, INR and
      creatinine) scores as well as scores to assess corticosteroid response in the
      management of alcoholic hepatitis. METHODS: A total of 182 patients were studied
      prospectively. The GAHS, MELD, ABIC and DF scores were recorded on admission and
      serially over the first week of hospital management. Treatment with
      corticosteroids or pentoxifylline was considered if the GAHS was >=9. RESULTS:
      There were no differences in outcome between favourable scores as per recommended
      cut-off points. Patients with a GAHS<9 had similar outcome whether their MELD, DF
      or ABIC scores were favourable or unfavourable. Treated patients with a GAHS>=9
      had a significantly better 90-day outcome than those who did not: 58% and 30%
      respectively, P = 0.01; HR 0.33 (0.14, 0.78). Patients treated with
      corticosteroids who had a fall in bilirubin of 25% after a week of treatment had
      an improved survival: 82% compared with 44% [P = 0.0005: HR 3.70 (1.77, 7.73)].
      The Lille Score or a 25% fall in bilirubin had greater sensitivities than an
      early change in bilirubin level (95% and 90% compared with 58%) to assess
      treatment response. CONCLUSIONS: In this single-centre study, a GAHS >=9
      identified patients who may benefit from treatment of alcoholic hepatitis.
      Intention-to-treat randomised-controlled trials using a GAHS >=9 as the threshold
      for treatment are needed to validate these findings. Response to corticosteroids
      can be assessed using the Lille Score or by a 25% fall in bilirubin.

PMID- 23879669
TI  - Structural properties of azobenzene self-assembled monolayers by atomistic
      simulations.
AB  - Azobenzene self-assembled monolayers (SAMs) are examples of optomechanical
      nanostructures capable of producing mechanical work through the well-known
      azobenzene photoisomerization process. Experimental studies have provided
      information on their structural properties, but an atomistic description of the
      SAMs in both the cis and trans forms is still lacking. In this work, a
      computational investigation of the SAM structures is conducted by classical
      molecular dynamics with a dedicated force. Experimental data on the SAM unit cell
      is used to set up SAM models of different molecular densities. The optimal
      structures are identified through the comparison with structural data from X-ray
      photoelectron and near-edge X-ray absorption fine structure spectroscopies. The
      resulting SAM atomistic models are validated by comparing simulated and
      experimental scanning tunneling microscopy images. 

PMID- 23879670
TI  - Regulation of the KstR2 regulon of Mycobacterium tuberculosis by a cholesterol
      catabolite.
AB  - Cholesterol catabolism is widespread in actinobacteria and is critical for
      Mycobacterium tuberculosis (Mtb) virulence. Catabolism of steroid nucleus rings C
      and D is poorly understood: it is initiated by the CoA thioesterification of
      3aalpha-H-4alpha(3'-propanoate)-7abeta-methylhexahydro-1,5-indanedione (HIP) by
      FadD3, whose gene is part of the KstR2 regulon. In Mtb, genes of this regulon
      were upregulated up to 30- and 22-fold during growth on cholesterol and HIP,
      respectively, versus another minimal medium. In contrast, genes involved in
      degrading the cholesterol side-chain and nucleus rings A and B were only
      upregulated during growth on cholesterol. Similar results were obtained in
      Rhodococcus jostii RHA1. Moreover, the regulon was not upregulated in a
      DeltafadD3 mutant unable to produce HIP-CoA. In electrophoretic mobility shift
      assays, HIP-CoA relieved the binding of KstR2(Mtb) to each of three KstR2 boxes:
      CoASH, HIP and a related CoA thioester did not. Inspection of the structure of
      KstR2(RHA1) revealed no obvious HIP-CoA binding pocket. The results establish
      that Mtb can catabolize the entire cholesterol molecule and that HIP-CoA is an
      effector of KstR2. They further indicate that KstR2 specifically represses the
      expression of the HIP degradation genes in actinobacteria, which encode a lower
      pathway involved in the catabolism of multiple steroids.

PMID- 23879671
TI  - Effects of azithromycin on intracellular cytokine responses and mucocutaneous
      manifestations in Behcet's disease.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of azithromycin
      on mucocutaneous manifestations and ex vivo intracellular cytokine responses in
      patients with Behcet's disease (BD). METHODS: Ten BD patients with active
      manifestations and nine healthy controls (HCs) were included in the study.
      Patients were treated with azithromycin (1500 mg/week) for four weeks. Clinical
      and immunological responses were evaluated in the pre- and post-azithromycin
      treatment periods. Peripheral blood mononuclear cells (PBMCs) of patients and
      controls were stimulated by Streptococcus sanguinis, lipopolysaccharide (LPS),
      lipoteichoic acid (LTA), and heat shock protein-60 (HSP-60) for three hours. Ex
      vivo intracellular interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha
      (TNF-alpha) levels were measured. RESULTS: Follicular lesions and genital ulcers
      completely healed, and the number of oral ulcers decreased after treatment (P =
      0.000). The stimulated intracellular IFN-gamma response to S. sanguinis was
      higher in BD patients (5.75%) than in HCs (3.9%) before treatment (P = 0.05).
      Likewise, the pretreatment IFN-gamma response was significantly higher than the
      post-treatment response (1.95%). In BD patients, pretreatment stimulated
      intracellular IFN-gamma responses to LTA (5.8%) were also higher than post
      treatment responses (3.15%), but the difference did not reach statistical
      significance (P = 0.07). CONCLUSIONS: Azithromycin treatment decreased the
      mucocutaneous manifestations in BD patients and suppressed the intracellular IFN
      gamma responses of PBMCs to S. sanguinis ex vivo, which suggests this treatment
      has an immunomodulatory effect.

PMID- 23879672
TI  - Facial expression discrimination varies with presentation time but not with
      fixation on features: a backward masking study using eye-tracking.
AB  - The current study investigated the effects of presentation time and fixation to
      expression-specific diagnostic features on emotion discrimination performance, in
      a backward masking task. While no differences were found when stimuli were
      presented for 16.67 ms, differences between facial emotions emerged beyond the
      happy-superiority effect at presentation times as early as 50 ms. Happy
      expressions were best discriminated, followed by neutral and disgusted, then
      surprised, and finally fearful expressions presented for 50 and 100 ms. While
      performance was not improved by the use of expression-specific diagnostic facial
      features, performance increased with presentation time for all emotions. Results
      support the idea of an integration of facial features (holistic processing)
      varying as a function of emotion and presentation time. 

PMID- 23879673
TI  - Modulatory ATP binding to the E2 state of maize plasma membrane H+-ATPase
      indicated by the kinetics of vanadate inhibition.
AB  - P-type ATPases, as major consumers of cellular ATP in eukaryotic cells, are
      characterized by the formation of a phosphorylated enzyme intermediate (E2P), a
      process that is allosterically coupled to translocation of cations against an
      electrochemical gradient. The catalytic cycle comprises binding of Mg-ATP at the
      nucleotide-binding domain, phosphorylation of the E1 state (E1), conformational
      transition to the E2P state, and dephosphorylation through the actuator domain
      and re-establishment of the E1 state. Recently, it has been suggested that, for
      several P-type ATPases, Mg-ATP binds to the phosphorylated enzyme, thereby
      accelerating the transition to the E1 state, before then becoming the enzyme's
      catalytic substrate. Here, we provide evidence supporting this viewpoint. We
      employed kinetic models based on steady-state kinetics in the presence and
      absence of the reversible inhibitor orthovanadate. Vanadate is generally
      considered to be a conformational probe that specifically binds to the E2 state,
      arresting the enzyme in a state analogous to the E2P state. Hydrolytic H(+) 
      ATPase activities were measured in inside-out plasma membrane vesicles isolated
      from roots and shoots of maize plants. For root enzymes, kinetic models of
      vanadate inhibition that allow simultaneous binding of Mg-ATP and vanadate to the
      same enzyme state were most plausible. For shoot enzymes, application of the
      competitive inhibitor Mg-free ATP attenuated vanadate inhibition, which is
      consistent with a model in which either Mg-free ATP or Mg-ATP is bound to the
      enzyme when vanadate binds. Therefore, data from roots and shoots indicate that
      binding of ATP species before transition to the E1 state plays an important role
      in the catalytic cycle of plant plasma membrane H(+) -ATPase. 

PMID- 23879674
TI  - Hematological study of patients with aphthous stomatitis.
AB  - OBJECTIVES: A study was made of the association between recurrent aphthosis (RAS)
      and iron, ferritin, vitamin B12, and folic acid deficiency. METHODS: A total of
      186 adults were consecutively recruited: 92 subjects with RAS (28 males and 64
      females, with a mean age of 41 years) and 94 controls (20 men and 74 women, with
      a mean age of 44 years), and subjected to clinical and hematological evaluation.
      RESULTS: The overall frequency of hematinic deficiencies was 14.14% in the RAS
      group versus 6.39% in the control group (P = 0.086). Patient age and a family
      history of aphthosis were associated to the presence of RAS. CONCLUSION: There is
      still no conclusive evidence relevant to the etiopathogenesis of RAS. Routine
      hematological screening and tests for serum iron, folic acid, and vitamin B12
      deficiencies should be assessed in all patients with RAS.

PMID- 23879675
TI  - A case of Goodpasture's syndrome complicating pregnancy with dialysis requiring
      renal failure responding to plasmapheresis and termination of pregnancy.
AB  - Goodpasture's syndrome complicating pregnancy is extremely rare and dialysis
      requiring anti GBM disease with renal recovery is uncommon. We report a case of a
      23-year-old primi gravida who presented with Goodpasture's syndrome during
      thirteenth week of pregnancy. She was initiated on steroids and cytotoxic drugs
      along with intensive plasma exchange and alternate day hemodialysis. Her
      pregnancy was terminated at 15 weeks. Patient improved dramatically with
      treatment, her renal functions normalized and her Anti GBM antibody titer became
      negative.

PMID- 23879676
TI  - Chemical bonding and aromaticity in furan, pyrrole, and thiophene: a magnetic
      shielding study.
AB  - Aromaticity and bonding in furan, pyrrole, and thiophene are investigated through
      the behavior of the isotropic shielding sigmaiso(r) within the regions of space
      surrounding these molecules. HF-GIAO/6-311++G(d,p) and MP2-GIAO/6-311++G(d,p)
      (Hartree-Fock and second-order Moller-Plesset perturbation theory utilizing gauge
      including atomic orbitals) sigmaiso(r) contour plots are constructed using
      regular two-dimensional 0.05 A grids in the molecular plane, in horizontal planes
      0.5 and 1 A above it, and in a vertical plane through the heteroatom. The nucleus
      independent chemical shifts (NICS) calculated at the ring centers and at 0.5 A
      and 1 A above these centers, NICS(0), NICS(0.5), and NICS(1), respectively,
      support the widely accepted order of aromaticities thiophene > pyrrole > furan.
      The results suggest that accurate NICS calculations benefit more from the use of
      an extended basis set than from the inclusion of dynamical electron correlation
      effects. The different extents of sigmaiso(r) delocalization observed in the
      horizontal contour plots and other features of sigmaiso(r) are also consistent
      with an aromaticity reduction of the order thiophene > pyrrole > furan. It is
      suggested that the extent of sigmaiso(r) delocalization in sigmaiso(r) contour
      plots in planes 1 A above the molecular plane could be used for comparing the
      relative aromaticities of a wide range of aromatic systems. 

PMID- 23879677
TI  - The effect of digitisation of the humeral epicondyles on quantifying elbow
      kinematics during cricket bowling.
AB  - In the sport of cricket the objective of the "no-ball" law is to allow no
      performance advantage through elbow extension during ball delivery. However,
      recently it has been shown that even bowlers with actions that are considered
      within the law show some elbow extension. The objective of this study was to
      investigate: [1] the effect of elbow orientation during anatomical landmark
      digitisation and [2] the choice of upper arm tracking cluster on the measurement
      of elbow angles during cricket bowling. We compared the mean elbow angles for
      four different elbow postures; with the joint flexed at approximately 130 degrees
      , 90 degrees , in full extension and with the elbow flexed with the humerus
      internally rotated, and two upper arm clusters in two different situations: [1]
      during a controlled movement of pure flexion-extension and [2] during cricket
      bowling. The digitised postures of the anatomical landmarks where the elbow was
      extended and at 90 degrees  of flexion were more repeatable than the other two
      postures. The recommendation of this study when analysing cricket bowling is to
      digitise the humeral epicondyles with the joint flexed at 90 degrees , or in full
      extension, and to relate their positions to an upper arm cluster fixed close to
      the elbow.

PMID- 23879678
TI  - Identification of candidate intergenic risk loci in autism spectrum disorder.
AB  - BACKGROUND: Copy number variations (CNVs) and DNA sequence alterations affecting
      specific neuronal genes are established risk factors for Autism Spectrum Disorder
      (ASD). In what is largely considered a genetic condition, so far, these mutations
      account for ~20% of individuals having an ASD diagnosis. However, non-coding
      genomic sequence also contains functional elements introducing additional disease
      risk loci for investigation. RESULTS: We have performed genome-wide analyses and
      identified rare inherited CNVs affecting non-genic intervals in 41 of 1491 (3%)
      of ASD cases examined. Examples of such intergenic CNV regions include 16q21 and
      2p16.3 near known ASD risk genes CDH8 and NRXN1 respectively, as well as novel
      loci contiguous with ZHX2, MOCS1, LRRC4C, SEMA3C, and other genes. CONCLUSIONS:
      Rare variants in intergenic regions may implicate new risk loci and genes in ASD
      and also present useful data for comparison with coming whole genome sequence
      datasets.

PMID- 23879679
TI  - Potassium channel openers and prostacyclin play a crucial role in mediating the
      vasorelaxant activity of Gynura procumbens.
AB  - BACKGROUND: Previous studies of Gynura procumbens (G. procumbens) have shown that
      partially purified fractions of the leaves are capable of lowering the blood
      pressure of rats by inhibiting angiotensin-converting enzymic activity and
      causing vasodilatation. The objectives of this study were therefore to further
      purify the active compounds that exhibited selective effects on blood vessels,
      determine the mechanism of actions, and to qualitatively analyse the putative
      compounds present. METHODS: The butanolic fraction (BU) of the crude ethanolic
      extract was purified using column chromatography to obtain several sub-fractions
      of different polarities. The in vitro effects of BU and the sub-fractions on
      vascular tension were subsequently determined using isolated rat thoracic aortic
      rings. The most potent sub-fraction (F1) alone was then investigated for its
      mechanisms of the vasorelaxant activity. In another experiment, thin-layer
      chromatography was used to qualitatively analyse the active compounds found in
      F1. RESULTS: The BU and the sub-fractions ranging from 10-7 to 10-2 g/ml
      significantly (p < 0.05) inhibited the sustained tonic contractions induced by
      phenylephrine and potassium chloride in a concentration-dependent manner with
      various degree of potency. The most potent sub-fraction (F1) antagonised the
      calcium-induced vasocontractions (1 x 10-4 - 1 x 10-2 M) in calcium-free with
      high concentration of potassium as well as in calcium- and potassium-free Krebs
      Henseleit solutions. Contractions induced by noradrenaline and caffeine were not
      affected by F1. The vasorelaxing effect caused by F1 was significantly attenuated
      with preincubation of potassium channel blockers (glibenclamide and 4
      aminopyridine) and prostacyclin inhibitor (indomethacin) while it was not
      affected by preincubation with tetraethylammonium, l-nitro-arginine methyl
      esther, propanolol, atropine, oxadiazolo quinoxalin one and methylene blue. The
      qualitative phytochemical analysis of F1 indicated the presence of flavonoids.
      CONCLUSION: These results confirm previous findings that G. procumbens causes
      vasodilatory effects by blocking calcium channels. In addition, the present study
      further demonstrates that the vasodilatory effect of G. procumbens may also be
      due to the opening of potassium channels and the stimulation of prostacyclin
      production. The putative compounds are probably flavonoids in nature.

PMID- 23879680
TI  - Systemic inflammatory response and local cytokine expression in porcine models of
      endocarditis.
AB  - The knowledge of systemic inflammation and local cytokine expression in porcine
      endocarditis models is limited, though it could provide valuable information
      about the pathogenesis and comparability to human endocarditis. Analyses of
      bacteriology and hematology were performed on blood samples from pigs with non
      bacterial thrombotic endocarditis (NBTE, n = 11), Staphylococcus aureus infective
      endocarditis (IE, n = 2), animals with S. aureus sepsis without endocarditis (n =
      2) and controls (n = 2). Furthermore, immunohistochemistry was used to examine
      the local expression of IL-1beta and IL-8. Bacterial blood cultures were
      continuously positive in IE pigs from inoculation to euthanasia, and negative in
      all other pigs at all times. The total white blood cell counts and total
      neutrophil counts were massively elevated in pigs with IE. Local IL-1beta and IL
      8 expression in IE pigs were moderate to high, and high, respectively. In
      addition, slight local expression of IL-1beta and IL-8 was present in some NBTE
      pigs. In the IE model, both the systemic inflammatory response and the high local
      expression of IL-8 were comparable to the human disease. Furthermore, the results
      indicate IL-1beta and IL-8 as important contributors in the endocarditis
      pathogenesis.

PMID- 23879681
TI  - Does variation in neurodegenerative disease susceptibility and phenotype reflect
      cerebral differences at the network level?
AB  - Alzheimer's disease (AD) is 10-fold more frequent than Parkinson's disease (PD),
      which in turn is 10-fold more frequent than amyotrophic lateral sclerosis (ALS).
      The differences between these neurodegenerative diseases have been ascribed to a
      selective vulnerability of specific neuronal sub-types that then determine each
      disorder. However, there are non-neuronal cells that are ubiquitously and
      possibly primarily involved in all of them, and they share regulatory mechanisms
      through similar interneurons and, typically inhibitory, neurotransmitters. There
      is recognized clinical and neuropathological overlap between AD, PD and ALS, the
      best example being Guamanian Lytico-Bodig, but increasingly recognized in larger
      populations, e.g. carriers of C9orf72 hexanucleotide expansions. From early
      embryogenesis to adulthood, genetic and experience-dependent functional neural
      networks develop primarily in relation to the neocortex. From an evolutionary
      standpoint, cognition, memory, executive function, linguistics and fine motor
      function are most prominent in humans. It is concluded that neural networks,
      rather than specific neuronal sub-types defined regionally or by individual
      transmitters, underlie the marked differences between neurodegenerative disorders
      in terms of susceptibility and clinical features. This requires the continued
      development of strategies to study brain function in health and disease as the
      'system', greater than the sum of its parts.

PMID- 23879682
TI  - Synthesis mechanism study of layered double hydroxides based on nanoseparation.
AB  - Colloidal layered double hydroxides (LDH) nanosheets were sorted by their lateral
      sizes using a density gradient ultracentrifuge separation technique. Composition
      investigations on these size-sorted nanosheets indicated that larger sheets had
      higher Mg:Al ratio than the smaller ones. Experiments using different Mg:Al feed
      ratios confirmed that high Mg:Al ratio induced fast sheet growth speed. Tracking
      the source of the Mg:Al spatial distribution difference in one batch of synthesis
      at the nucleation process revealed the coprecipitation-redissolution of Mg(2+).
      Thus the discriminative separation of these nanosheets led to a new insight into
      the structure-composition relationship of LDH nanomaterials and more
      understanding on their formation mechanism. 

PMID- 23879683
TI  - Porous polymer nanostructures fabricated by the surface-induced phase separation
      of polymer solutions in anodic aluminum oxide templates.
AB  - We study the formation of porous polymer nanostructures fabricated by the surface
      induced phase separation of polymer solutions in anodic aluminum oxide (AAO)
      templates. Poly(methyl methacrylate) (PMMA) and tetrahydrofuran (THF) are used to
      investigate the evolution process of the surface-induced phase separation. With
      the longer immersion time of the AAO template in the polymer solution, the size
      of the solvent-rich droplet is increased by the coarsening process, resulting in
      the formation of porous polymer nanostructures. The coarsening mechanism is
      further evaluated by changing the experimental parameters including the immersion
      time, the polymer concentration, the polymer molecular weight, and the solvent
      quality. Under conditions in which polymer solutions have higher viscosities, the
      coarsening process is slowed down and the formation of the porous nanostructures
      is prohibited. The prevention of the porous nanostructures can also be realized
      by adding water to the PMMA/THF solution before the immersion process. 

PMID- 23879684
TI  - Multi-walled carbon nanotubes decorated by platinum catalyst nanoparticles-
      examination and microanalysis using scanning and transmission electron
      microscopies.
AB  - Carbon nanotubes (CNTs) decorated with platinum (Pt) nanoparticles (NPs) have
      been characterized using a cold field-emission scanning electron microscope (SEM)
      and a high resolution field-emission transmission electron microscope (TEM). With
      this particular composite material, the complementary nature of the two
      instruments was demonstrated. Although the long CNTs were found to be mostly bent
      and defective in some parts, the nucleation of Pt occurred randomly and uniformly
      covered the CNTs. The NPs displayed a large variation in size, were sometimes
      defective with twins and stacking faults, and were found to be faceted with the
      presence of surface steps. The shape and size of the NPs and the presence of
      defects may have significant consequences on the activity of the Pt catalyst
      material. Also, thin layers of platinum oxide were identified on the surface of
      some NPs. 

PMID- 23879685
TI  - Characterization of a new pathogenic Acanthamoeba Species, A. byersi n. sp.,
      isolated from a human with fatal amoebic encephalitis.
AB  - Acanthamoeba spp. are free-living amoebae that are ubiquitous in natural
      environments. They can cause cutaneous, nasopharyngeal, and disseminated
      infection, leading to granulomatous amebic encephalitis (GAE) in
      immunocompromised individuals. In addition, they can cause amoebic keratitis in
      contact lens wearers. Acanthamoeba GAE is almost always fatal because of
      difficulty and delay in diagnosis and lack of optimal antimicrobial therapy.
      Here, we report the description of an unusual strain isolated from skin and brain
      of a GAE patient. The amoebae displayed large trophozoites and star-shaped cysts,
      characteristics for acanthamoebas belonging to morphology Group 1. However, its
      unique morphology and growth characteristics differentiated this new strain from
      other Group 1 species. DNA sequence analysis, secondary structure prediction, and
      phylogenetic analysis of the 18S rRNA gene confirmed that this new strain
      belonged to Group 1, but that it was distinct from the other sequence types
      within that group. Thus, we hereby propose the establishment of a new species,
      Acanthamoeba byersi n. sp. as well as a new sequence type, T18, for this new
      strain. To our knowledge, this is the first report of a Group 1 Acanthamoeba that
      is indisputably pathogenic in humans. 

PMID- 23879686
TI  - Cerebellar networks with basal ganglia: feasibility for tracking cerebello
      pallidal and subthalamo-cerebellar projections in the human brain.
AB  - Neuroanatomical studies using transneuronal virus tracers in macaque monkeys
      recently demonstrated that substantial interactions exist between basal ganglia
      and the cerebellum. To what extent these interactions are present in the human
      brain remains unclear; however, these connections are thought to provide an
      important framework for understanding cerebellar contributions to the
      manifestation of basal ganglia disorders, especially with respect to tremor
      genesis in movement disorders such as Parkinson's disease. Here, we tested the
      feasibility of assessing these connections in vivo and non-invasively in the
      human brain with diffusion magnetic resonance imaging and tractography. After
      developing a standardized protocol for manual segmentation of basal ganglia and
      cerebellar structures, masks for diffusion tractography were defined based on
      structural magnetic resonance images. We tested intra- and inter-observer
      stability and carried out tractography for dentato-pallidal and subthalamo
      cerebellar projections. After robustly achieving connection probabilities per
      tract, the connectivity values and connectional fingerprints were calculated in a
      group of healthy volunteers. Probabilistic diffusion tractography was applicable
      to probe the inter-connection of the cerebellum and basal ganglia. Our data
      confirmed that dentato-thalamo-striato-pallidal and subthalamo-cerebellar
      connections also exist in the human brain at a level similar to those that were
      recently suggested by transneuronal tracing studies in non-human primates.
      Standardized segmentation protocols made these findings reproducible with high
      stability. We have demonstrated that diffusion tractography in humans in vivo is
      capable of revealing the structural bases of cerebellar networks with the basal
      ganglia. These findings support the role of the cerebellum as a satellite system
      of established cortico-basal ganglia networks in humans. 

PMID- 23879687
TI  - Solid-state 17O NMR of pharmaceutical compounds: salicylic acid and aspirin.
AB  - We report solid-state NMR characterization of the (17)O quadrupole coupling (QC)
      and chemical shift (CS) tensors in five site-specifically (17)O-labeled samples
      of salicylic acid and o-acetylsalicylic acid (Aspirin). High-quality (17)O NMR
      spectra were obtained for these important pharmaceutical compounds under both
      static and magic angle spinning (MAS) conditions at two magnetic fields, 14.0 and
      21.1 T. A total of 14 (17)O QC and CS tensors were experimentally determined for
      the seven oxygen sites in salicylic acid and Aspirin. Although both salicylic
      acid and Aspirin form hydrogen bonded cyclic dimers in the solid state, we found
      that the potential curves for the concerted double proton transfer in these two
      compounds are significantly different. In particular, while the double-well
      potential curve in Aspirin is nearly symmetrical, it is highly asymmetrical in
      salicylic acid. This difference results in quite different temperature
      dependencies in (17)O MAS spectra of the two compounds. A careful analysis of
      variable-temperature (17)O MAS NMR spectra of Aspirin allowed us to obtain the
      energy asymmetry (DeltaE) of the double-well potential, DeltaE = 3.0 +/- 0.5
      kJ/mol. We were also able to determine a lower limit of DeltaE for salicylic
      acid, DeltaE > 10 kJ/mol. These asymmetrical features in potential energy curves
      were confirmed by plane-wave DFT computations, which yielded DeltaE = 3.7 and
      17.8 kJ/mol for Aspirin and salicylic acid, respectively. To complement the solid
      state (17)O NMR data, we also obtained solid-state (1)H and (13)C NMR spectra for
      salicylic acid and Aspirin. Using experimental NMR parameters obtained for all
      magnetic nuclei present in salicylic acid and Aspirin, we found that plane-wave
      DFT computations can produce highly accurate NMR parameters in well-defined
      crystalline organic compounds. 

PMID- 23879688
TI  - Maximising use of social media for patient and professional interaction.

PMID- 23879690
TI  - Asymmetric synthesis of congested spiro-cyclopentaneoxindoles via an
      organocatalytic cascade reaction.
AB  - Starting from simple alkylidene oxindoles and nitroketones, a highly
      stereoselective methodology was developed for the synthesis of spiro
      cyclopentaneoxindoles with four consecutive stereogenic centers. Using an
      organocatalytic cascade of Michael and aldol reactions in the presence of a
      chiral thiourea catalyst products were obtained in moderate to high yields and
      excellent enantioselectivities. Nitro, ester, and hydroxyl groups were introduced
      to the spiro ring, which could be used to facilitate further functionalization of
      the products. 

PMID- 23879689
TI  - A role for the copper transporter Ctr1 in the synergistic interaction between
      hyperthermia and cisplatin treatment.
AB  - PURPOSE: Hyperthermia enhances cytotoxic effects of chemotherapeutic agents such
      as cisplatin. However, the underlying molecular mechanisms remain unclear. We
      hypothesised that hyperthermia increases cisplatin accumulation and efficacy by
      modulating function of copper transport protein 1 (Ctr1), a major regulator of
      cellular cisplatin uptake. We examined the significance of Ctr1 in the
      synergistic interaction between hyperthermia and cisplatin. We assessed the
      importance of cisplatin- and hyperthermia-induced Ctr1 multimerisation in
      sensitising cells to cisplatin cytotoxicity. MATERIALS AND METHODS: Ctr1 protein
      levels and cisplatin sensitivities were assessed in bladder cancer cell lines
      with immunoblotting and clonogenic survival assays. Using Myc-tagged-Ctr1 HEK293
      cells, we assessed the effect of hyperthermia on Ctr1 multimerisation with
      immunoblotting. The effect of hyperthermia on cisplatin sensitivity and
      accumulation was assessed in wild-type (WT) and Ctr1 knockout (Ctr1-/-) mouse
      embryonic fibroblasts (MEFs) with clonogenic assays and inductively coupled
      plasma-mass spectrometry (ICP-MS). RESULTS: Increased Ctr1 protein expression was
      observed for the most cisplatin-sensitive bladder cancer cell lines and MEFs.
      Heat-induced increase in Ctr1 multimerisation with cisplatin was observed in Myc
      tagged Ctr1 cells. Hyperthermia enhanced cisplatin-mediated cytotoxicity in WT
      more than Ctr1-/- cells (dose modifying factors 1.75 versus 1.4, respectively).
      WT cells accumulated more platinum versus Ctr1-/- cells; this was further
      increased by hyperthermia in WT cells. CONCLUSIONS: Hyperthermia enhanced
      cisplatin uptake and cytotoxicity in WT cells. Heat increased Ctr1 activity by
      increasing multimerisation, enhancing drug cytotoxicity. Furthermore, Ctr1
      protein profiles of bladder tumours, as well as other tumour types, may predict
      their response to cisplatin and overall efficacy of treatment.

PMID- 23879691
TI  - Free radicals and sprint exercise in humans.
AB  - Sprint exercise ability has been critical for survival. The remarkably high-power
      output levels attained during sprint exercise are achieved through strong
      activation of anaerobic, and to a lesser extent, aerobic energy supplying
      metabolic reactions, which generate reactive oxygen and nitrogen species (RONS).
      Sprint exercise may cause oxidative stress leading to muscle damage, particularly
      when performed in severe acute hypoxia. However, with training oxidative stress
      is reduced. Paradoxically, total plasma antioxidant capacity increases during the
      subsequent 2 h after a short sprint due to the increase in plasma urate
      concentration. The RONS produced during and immediately after sprint exercise
      play a capital role in signaling the adaptive response to sprint. Antioxidant
      supplementation blunts the normal AMPKalpha and CaMKII phosphorylation in
      response to sprint exercise. However, under conditions of increased glycolytic
      energy turnover and muscle acidification, as during sprint exercise in severe
      acute hypoxia, AMPKalpha phosphorylation is also blunted. This indicates that an
      optimal level of RONS-mediated stimulation is required for the normal signaling
      response to sprint exercise. Although RONS are implicated in fatigue, most
      studies convey that antioxidants do not enhance sprint performance in humans.
      Although currently controversial, it has been reported that antioxidant ingestion
      during training may jeopardize some of the beneficial adaptations to sprint
      training.

PMID- 23879692
TI  - Membrane association of a protein increases the rate, extent, and specificity of
      chemical cross-linking.
AB  - Many cellular processes involve interactions between membrane-associated
      proteins, and those interactions are enhanced by membrane association. We have
      used cross-linking reactions to compare the extent and specificity of protein
      interactions in solution versus on a membrane surface. Cysteine mutants of a
      soluble cytoplasmic fragment (CF) of the aspartate receptor, a transmembrane
      receptor involved in bacterial chemotaxis, are used in disulfide bond formation
      with the thiol-specific oxidant diamide and chemical cross-linking reactions with
      the trifunctional maleimide TMEA. CF binding to membranes is mediated by its N
      terminal His tag binding to vesicles containing a nickel-chelating lipid, so
      cross-linking reactions conducted in the presence and absence of vesicles differ
      only in whether CF is bound to the vesicles or is free in solution. For multiple
      Cys throughout the CF, membrane association is shown to increase the rate and
      extent of these reactions. Cross-linking specificity, which is measured as the
      preference for cross-linking between Cys near each other in the native structure,
      is also enhanced by membrane association. These results provide an experimental
      demonstration that membrane binding enhances protein-protein interactions, an
      important consideration for understanding processes involving membrane-associated
      proteins. The experiments further demonstrate the importance of cross-linking
      conditions for these reactions that are often used to probe protein structure and
      dynamics and the potential of membrane association to restore native interactions
      of membrane-associated proteins for cross-linking studies. 

PMID- 23879693
TI  - Using principal component analysis in studying the transdermal delivery of a
      lipophilic drug from soft nano-colloidal carriers to develop a quantitative
      composition effect permeability relationship.
AB  - The aim of principal component analysis is to reduce the dimensionality of the
      data while retaining its variation. Obtaining a vector component representing the
      most important variation amongst the data and summarizing the factors are usually
      needed to achieve a new descriptor for the system. This can be used to elaborate
      certain properties related to the components used in formulating drug delivery
      systems. To this end, it is possible to develop what exclusively can be called
      quantitative composition effect permeability relationship. In this study,
      fundamental features of the Fourier transform infrared spectroscopy together with
      the degree of saturation of a model drug, testosterone hormone, were used as
      initial dimensions and their extent of change were utilized as original variables
      to generate a correlation matrix. The principal component (PC) with the largest
      eigen value was selected for regression analysis to provide a quantitative model
      relating the effects of different compositions with the enhanced penetration of
      the model lipophilic drug from microemulsions. A strong correlation (r = 0.90)
      was obtained between the main PC derived data and the observed permeability
      coefficient results which warrants the use of this analyzing method in optimizing
      different drug delivery systems.

PMID- 23879695
TI  - Sleep, sleepiness, and neurobehavioral performance while on watch in a simulated
      4 hours on/8 hours off maritime watch system.
AB  - Seafarer sleepiness jeopardizes safety at sea and has been documented as a direct
      or contributing factor in many maritime accidents. This study investigates sleep,
      sleepiness, and neurobehavioral performance in a simulated 4 h on/8 h off watch
      system as well as the effects of a single free watch disturbance, simulating a
      condition of overtime work, resulting in 16 h of work in a row and a missed sleep
      opportunity. Thirty bridge officers (age 30 +/- 6 yrs; 29 men) participated in
      bridge simulator trials on an identical 1-wk voyage in the North Sea and English
      Channel. The three watch teams started respectively with the 00-04, the 04-08,
      and the 08-12 watches. Participants rated their sleepiness every hour (Karolinska
      Sleepiness Scale [KSS]) and carried out a 5-min psychomotor vigilance test (PVT)
      test at the start and end of every watch. Polysomnography (PSG) was recorded
      during 6 watches in the first and the second half of the week. KSS was higher
      during the first (mean +/- SD: 4.0 +/- 0.2) compared with the second (3.3 +/-
      0.2) watch of the day (p < 0.001). In addition, it increased with hours on watch
      (p < 0.001), peaking at the end of watch (4.1 +/- 0.2). The free watch
      disturbance increased KSS profoundly (p < 0.001): from 4.2 +/- 0.2 to 6.5 +/-
      0.3. PVT reaction times were slower during the first (290 +/- 6 ms) compared with
      the second (280 +/- 6 ms) watch of the day (p < 0.001) as well as at the end of
      the watch (289 +/- 6 ms) compared with the start (281 +/- 6 ms; p = 0.001). The
      free watch disturbance increased reaction times (p < 0.001) from 283 +/- 5 to 306
      +/- 7 ms. Similar effects were observed for PVT lapses. One third of all
      participants slept during at least one of the PSG watches. Sleep on watch was
      most abundant in the team working 00-04 and it increased following the free watch
      disturbance. This study reveals that-within a 4 h on/8 h off shift system
      subjective and objective sleepiness peak during the night and early morning
      watches, coinciding with a time frame in which relatively many maritime accidents
      occur. In addition, we showed that overtime work strongly increases sleepiness.
      Finally, a striking amount of participants fell asleep while on duty. 

PMID- 23879694
TI  - Improving understanding in the research informed consent process: a systematic
      review of 54 interventions tested in randomized control trials.
AB  - BACKGROUND: Obtaining informed consent is a cornerstone of biomedical research,
      yet participants comprehension of presented information is often low. The most
      effective interventions to improve understanding rates have not been identified.
      PURPOSE: To systematically analyze the random controlled trials testing
      interventions to research informed consent process. The primary outcome of
      interest was quantitative rates of participant understanding; secondary outcomes
      were rates of information retention, satisfaction, and accrual. Interventional
      categories included multimedia, enhanced consent documents, extended discussions,
      test/feedback quizzes, and miscellaneous methods. METHODS: The search spanned
      from database inception through September 2010. It was run on Ovid MEDLINE, Ovid
      EMBASE, Ovid CINAHL, Ovid PsycInfo and Cochrane CENTRAL, ISI Web of Science and
      Scopus. Five reviewers working independently and in duplicate screened full
      abstract text to determine eligibility. We included only RCTs. 39 out of 1523
      articles fulfilled review criteria (2.6%), with a total of 54 interventions. A
      data extraction form was created in Distiller, an online reference management
      system, through an iterative process. One author collected data on study design,
      population, demographics, intervention, and analytical technique. RESULTS: Meta
      analysis was possible on 22 interventions: multimedia, enhanced form, and
      extended discussion categories; all 54 interventions were assessed by review.
      Meta-analysis of multimedia approaches was associated with a non-significant
      increase in understanding scores (SMD 0.30, 95% CI, -0.23 to 0.84); enhanced
      consent form, with significant increase (SMD 1.73, 95% CI, 0.99 to 2.47); and
      extended discussion, with significant increase (SMD 0.53, 95% CI, 0.21 to 0.84).
      By review, 31% of multimedia interventions showed significant improvement in
      understanding; 41% for enhanced consent form; 50% for extended discussion; 33%
      for test/feedback; and 29% for miscellaneous.Multiple sources of variation
      existed between included studies: control processes, the presence of a human
      proctor, real vs. simulated protocol, and assessment formats. CONCLUSIONS:
      Enhanced consent forms and extended discussions were most effective in improving
      participant understanding. Interventions of all categories had no negative impact
      on participant satisfaction or study accrual. Identification of best practices
      for studies of informed consent interventions would aid future systematic
      comparisons.

PMID- 23879696
TI  - Melatonin treatment entrains the rest-activity circadian rhythm in rats with
      chronic inflammation.
AB  - We assessed the therapeutic effect of exogenous melatonin (MEL), dexamethasone
      (DEXA), and a combination of both on nociceptive response induced by chronic
      inflammation and on the rest-activity circadian rhythm in rats. A total of 64
      animals were randomly divided into eight groups of eight rats each: one control
      group and seven groups with complete Freund's adjuvant-inflamed animals (CFA;
      injection into the footpad). One of the CFA-inflamed groups did not receive any
      treatment; the other six were treated with melatonin (MEL), dexamethasone (DEXA),
      melatonin plus dexamethasone (MELDEXA), and their respective vehicles. Fifteen
      days after CFA injection, animals were treated with intraperitoneal injection of
      MEL (50 mg/kg) or its vehicle (8% ethanol in saline), DEXA (0.25 mg/kg) or its
      vehicle (saline), and MEL plus DEXA or their vehicles, for 8 days. The von Frey
      test was performed 24 h after the last administration of each treatment regimen.
      Hind paw thickness was measured using a pachymeter during the treatment days. The
      degree of swelling and histological findings were analyzed. All treated groups
      significantly reduced the severity of inflammation when compared with their
      vehicles (repeated-measures analysis of variance [ANOVA], p < 0.05 for all
      analyses). Inflamed animals treated with dexamethasone alone or associated with
      melatonin showed marked inhibition of histological findings. On the other hand,
      the group treated with melatonin remained with moderate inflammation. The CFA
      group showed a decrease in the mean rest-activity circadian rhythm, determined by
      the number of touch-detections per hour during water intake in comparison with
      the control group; only the group treated with melatonin showed a synchronized
      rest-activity rhythm. At the end of treatment, a significant increase was
      observed in hind paw withdrawal threshold on the von Frey test in the treated
      groups (one-way ANOVA, p < 0.05 for all). Our findings showed that melatonin (50
      mg/kg) has strong chronobiotic and antinociceptive effects, but only mild anti
      inflammatory effects. This evidence supports the hypothesis that melatonin can
      induce phase advance and circadian rhythm synchronization in rats with chronic
      inflammation. 

PMID- 23879697
TI  - Photoperiod affects the diurnal rhythm of hippocampal neuronal morphology of
      Siberian hamsters.
AB  - Individuals of many species can regulate their physiology, morphology, and
      behavior in response to annual changes of day length (photoperiod). In mammals,
      the photoperiodic signal is mediated by a change in the duration of melatonin,
      leading to alterations in gene expressions, neuronal circuits, and hormonal
      secretion. The hippocampus is one of the most plastic structures in the adult
      brain and hippocampal neuronal morphology displays photoperiod-induced
      differences. Because the hippocampus is important for emotional and cognitive
      behaviors, photoperiod-driven remodeling of hippocampal neurons is implicated in
      seasonal differences of affect, including seasonal affective disorder (SAD) in
      humans. Because neuronal architecture is also affected by the day-night cycle in
      several brain areas, we hypothesized that hippocampal neuronal morphology would
      display a diurnal rhythm and that day length would influence that rhythm. In the
      present study, we examined diurnal and seasonal differences in hippocampal
      neuronal morphology, as well as mRNA expression of the neurotrophic factors
      (i.e., brain-derived neurotrophic factor [Bdnf], tropomyosin receptor kinase B
      [trkB; a receptor for BDNF], and vascular endothelial growth factor [Vegf]) and a
      circadian clock gene, Bmal1, in the hippocampus of Siberian hamsters. Diurnal
      rhythms in total length of dendrites, the number of primary dendrites, dendritic
      complexity, and distance of the furthest intersection from the cell body were
      observed only in long-day animals; however, diurnal rhythms in the number of
      branch points and mean length of segments were observed only in short-day
      animals. Spine density of dendrites displayed diurnal rhythmicity with different
      peak times between the CA1 and DG subregions and between long and short days.
      These results indicate that photoperiod affects daily morphological changes of
      hippocampal neurons and the daily rhythm of spine density, suggesting the
      possibility that photoperiod-induced adjustments of hippocampal neuronal dynamics
      might underlie seasonal difference of affective responses. Bmal1 mRNA showed a
      diurnal rhythm and different expression levels between long and short days were
      observed. However, there were no strong effects of day length on Bdnf. trkb, and
      Vegf gene expression, suggesting that these genes are not involved in the
      photoperiodic effects on hippocampal neurons. 

PMID- 23879698
TI  - Cutaneous neonatal lupus: a case report and review of the literature.

PMID- 23879699
TI  - Review article: the role of gastrointestinal hormones in the treatment of delayed
      gastric emptying in critically ill patients.
AB  - BACKGROUND: Delayed gastric emptying limits the administration of enteral
      nutrition, leading to malnutrition, which is associated with higher mortality and
      morbidity. Currently available prokinetics have limitations in terms of sustained
      efficacy and side effects. AIM: To summarise the mechanisms of action and to
      discuss the possible utility of gastrointestinal hormones to prevent or treat
      delayed gastric emptying in critically ill patients. METHODS: We searched PubMed
      for articles discussing 'delayed gastric emptying', 'enteral nutrition',
      'treatment', 'gastrointestinal hormones', 'prokinetic', 'agonist', 'antagonist'
      and 'critically ill patients'. RESULTS: Motilin and ghrelin receptor agonists
      initiate the migrating motor complex in the stomach, which accelerates gastric
      emptying. Cholecystokinin, glucagon-like peptide-1 and peptide YY have an
      inhibiting effect on gastric emptying; therefore, antagonising these
      gastrointestinal hormones may have therapeutic potential. Other gastrointestinal
      hormones appear less promising. CONCLUSIONS: Manipulation of endogenous
      secretion, physiological replacement and administration of gastrointestinal
      hormones in pharmacological doses is likely to have therapeutic potential in the
      treatment of delayed gastric emptying. Future challenges in this field will
      include the search for candidates with improved selectivity and favourable
      kinetic properties.

PMID- 23879700
TI  - Multiple familial trichoepithelioma: report of a Chinese family not associated
      with a mutation in the CYLD gene and CYLD protein expression in the
      trichoepithelioma tumor tissue.

PMID- 23879702
TI  - Fluorescent self-assembled monolayers of umbelliferone: a relationship between
      contact angle and fluorescence.
AB  - Self-assembled monolayers (SAMs) that contain fluorophore units are nowadays
      widely used to tune surface properties and design new chemical sensor chips. It
      is well-known that the nature of the substrate may strongly interfere with the
      emission properties of the grafted molecules, but the organization of the
      monolayer may also have an important role. To study the influence of the SAM
      organization on the luminescence properties, we prepared different coumarin-based
      derivatives endowed with tethered chains of different lengths and elaborated the
      corresponding SAMs on glass slides. Besides SAM structural characterizations by
      atomic force microscopy and X-ray reflectivity, we carried out contact angle
      measurements and applied the Van Oss-Chaudhury-Good theory, which was rarely used
      previously for self-assembled monolayers. As expected, by increasing the tethered
      chain length, a higher surface coverage, a higher degree of organization, and a
      stronger molecular packing were observed. However, it appears to facilitate the
      self-quenching process, and thus, this strongly affects the fluorescent
      properties of the SAMs. 

PMID- 23879701
TI  - A novel dental implant guided surgery based on integration of surgical template
      and augmented reality.
AB  - BACKGROUND: Stereoscopic visualization concept combined with head-mounted
      displays may increase the accuracy of computer-aided implant surgery. PURPOSE:
      The aim of this study was to develop an augmented reality-based dental implant
      placement system and evaluate the accuracy of the virtually planned versus the
      actual prepared implant site created in vitro. MATERIALS AND METHODS: Four fully
      edentulous mandibular and four partially edentulous maxillary duplicated casts
      were used. Six implants were planned in the mandibular and four in the maxillary
      casts. A total of 40 osteotomy sites were prepared in the casts using
      stereolithographic template integrated with augmented reality-based surgical
      simulation. During the surgery, the dentist could be guided accurately through a
      head-mounted display by superimposing the virtual auxiliary line and the drill
      stop. The deviation between planned and prepared positions of the implants was
      measured via postoperative computer tomography generated scan images. RESULTS:
      Mean and standard deviation of the discrepancy between planned and prepared sites
      at the entry point, apex, angle, depth, and lateral locations were 0.50 +/- 0.33
      mm, 0.96 +/- 0.36 mm, 2.70 +/- 1.55 degrees , 0.33 +/- 0.27 mm, and 0.86 +/- 0.34
      mm, respectively, for the fully edentulous mandible, and 0.46 +/- 0.20 mm, 1.23
      +/- 0.42 mm, 3.33 +/- 1.42 degrees , 0.48 +/- 0.37 mm, and 1.1 +/- 0.39 mm,
      respectively, for the partially edentulous maxilla. There was a statistically
      significant difference in the apical deviation between maxilla and mandible in
      this surgical simulation (p < .05). CONCLUSIONS: Deviation of implant placement
      from planned position was significantly reduced by integrating surgical template
      and augmented reality technology.

PMID- 23879703
TI  - New mechanism for the ring-opening polymerization of lactones? Uranyl aryloxide
      induced intermolecular catalysis.
AB  - The uranyl aryloxide [UO2(OAr)2(THF)2] (Ar = 2,6-(t)Bu2-C6H2) is an active
      catalyst for the ring-opening cyclo-oligomerization of epsilon-caprolactone and
      delta-valerolactone but not for beta-butyrolactone, gamma-butyrolactone, and rac
      lactide. (1)H EXSY measurements give the thermodynamic parameters for exchange of
      monomer and coordinated THF, and rates of polymerization have been determined. A
      comprehensive theoretical examination of the mechanism is discussed. From both
      experiment and theory, the initiation step is intramolecular and in keeping with
      the accepted mechanism, while computational studies indicate that propagation can
      go via an intermolecular pathway, which is the first time this has been observed.
      The lack of polymerization for the inactive monomers has been investigated
      theoretically and C-H...pi interactions stabilize the coordination of the less
      rigid monomers. 

PMID- 23879704
TI  - Molecular microbiological evaluation of subgingival biofilm sampling by paper
      point and curette.
AB  - The present clinical study aimed to investigate if there are differences in
      microbiological outcomes dependent on the subgingival biofilm collection method.
      Subgingival biofilm samples were collected from the four deepest pockets (>5 mm)
      of 17 patients with aggressive periodontitis (AgP) and 33 patients with chronic
      periodontitis (CP), first by paper point and thereafter by curette. Samples
      obtained with the same method were pooled together from each patient and
      forwarded for molecular microbiological analysis by a commercially available
      assay (IAI Pado Test 4.5) that estimates total bacterial load and levels of
      Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola and
      Aggregatibacter actinomycetemcomitans. Data analysis included frequency of
      detection, quantification and correlation of detection levels between the two
      sampling methods. P. gingivalis, T. forsythia and T. denticola were detected in
      >90% of the samples, and their detection levels exhibited a strong correlation
      between sampling methods. The detection consistency of A. actinomycetemcomitans
      was 56% between the two sampling methods. A. actinomycetemcomitans was more
      readily detected by paper point compared with curette collection with a stronger
      correlation between the two methods in AgP. Subgingival biofilm sampling by
      curette or paper point does not yield differences in the detection of the three
      'red complex' species. However, A. actinomycetemcomitans was more consistently
      detected by means of paper point collection, which can be crucial in the decision
      to administer antibiotics as an adjunctive periodontal treatment.

PMID- 23879705
TI  - Long-term response to peginterferon in hepatitis C virus-associated nephrotic
      syndrome from focal segmental glomerulosclerosis.
AB  - Hepatitis C virus (HCV) infection is a global public health problem. Chronic HCV
      infection is an important cause of chronic liver disease. Since the first
      reported association between HCV and membranoproliferative glomerulonephritis
      (MPGN) in 1993, HCV has been described with other types of glomerular diseases,
      although less frequently. Focal segmental glomerulosclerosis (FSGS) is one such
      glomerular disease that has been rarely reported in association with HCV.
      Antiviral therapy with interferon and ribavirin has been shown to be beneficial
      in HCV-associated MPGN. The optimal therapy of HCV-associated FSGS is not
      currently known. To our knowledge, long-term response to pegylated interferon
      monotherapy in treatment of HCV-associated FSGS has not been reported. We report
      an adult patient with HCV-associated FSGS who presented with nephrotic syndrome
      and renal failure. Treatment with pegylated interferon alfa-2a monotherapy
      resulted in sustained virological response with a clinical remission of nephrotic
      syndrome and stabilization of renal function. Patient continued to remain in
      clinical remission of nephrotic syndrome with stable renal function, 5 years
      after treatment. We also briefly review the literature on HCV-associated
      glomerular diseases, particularly HCV-associated FSGS.

PMID- 23879708
TI  - Authority defied: need for cognitive closure influences regulatory control when
      resisting authority.
AB  - The present studies examined whether differences in need for cognitive closure
      (NCC) were related to differences in regulatory control when confronted with
      authority. In two studies, levels of regulatory control were measured when
      participants resisted (Study 1; N = 46) or prepared to resist the influence
      attempt of an authority figure (Study 2; N = 50). Results showed that resisting
      the influence attempt from a high-authority figure was more depleting for
      participants higher in NCC compared to individuals lower in NCC. However, when
      they were given instructions and time to prepare the act of resistance,
      individuals high in NCC actually showed an increase in regulatory control.
      Authority is usually viewed as a general principle of influence; however, the
      present studies suggest that there are individual differences that influence how
      people may experience interactions with authorities. 

PMID- 23879709
TI  - Fatigue effects upon sticking region and electromyography in a six-repetition
      maximum bench press.
AB  - The aim of the study was to examine the sticking region and concomitant
      neuromuscular activation of the prime movers during six-repetition maximum (RM)
      bench pressing. We hypothesised that both peak velocities would decrease and that
      the electromyography (EMG) of the prime movers (deltoid, major pectoralis and
      triceps) would increase during the pre-sticking and sticking region during the
      six repetitions due to fatigue. Thirteen resistance-trained males (age 22.8 +/-
      2.2 years, stature 1.82 +/- 0.06 m, body mass 83.4 +/- 7.6 kg) performed 6-RM
      bench presses. Barbell kinematics and EMG activity of pectoralis major, deltoid
      anterior, and triceps brachii during the pre-, sticking and post-sticking region
      of each repetition in a 6-RM bench press were analysed. For both the sticking as
      the post-sticking region, the time increased significantly from the first to the
      sixth repetition. Vertical barbell height at the start of sticking region was
      lower, while the height at the end of the sticking region and post-sticking
      region did not change during the six repetitions. It was concluded that in 6-RM
      bench pressing performance, the sticking region is a poor mechanical force region
      due to the unchanged barbell height at the end of the sticking region.
      Furthermore, when fatigue occurs, the pectoralis and the deltoid muscles are
      responsible for surpassing the sticking region as indicated by their increased
      activity during the pre- and sticking region during the six-repetitions bench
      press.

PMID- 23879707
TI  - Evidence of antimicrobial resistance-conferring genetic elements among
      pneumococci isolated prior to 1974.
AB  - BACKGROUND: Antimicrobial resistance among pneumococci has greatly increased over
      the past two to three decades. Resistance to tetracycline (tet(M)),
      chloramphenicol (cat) and macrolides (erm(B) and/or mef(A/E)) is generally
      conferred by acquisition of specific genes that are associated with mobile
      genetic elements, including those of the Tn916 and Tn5252 families. The first
      tetracycline-, chloramphenicol- and macrolide-resistant pneumococci were detected
      between 1962 and 1970; however, until now the oldest pneumococcus shown to
      harbour Tn916 and/or Tn5252 was isolated in 1974. In this study the genomes of 38
      pneumococci isolated prior to 1974 were probed for the presence of tet(M), cat,
      erm(B), mef(A/E) and int (integrase) to indicate the presence of Tn916/Tn5252
      like elements. RESULTS: Two Tn916-like, tet(M)-containing, elements were
      identified among pneumococci dated 1967 and 1968. The former element was highly
      similar to that of the PMEN1 multidrug-resistant, globally-distributed
      pneumococcal reference strain, which was isolated in 1984. The latter element was
      associated with a streptococcal phage. A third, novel genetic element, designated
      ICESpPN1, was identified in the genome of an isolate dated 1972. ICESpPN1
      contained a region of similarity to Tn5252, a region of similarity to a
      pneumococcal pathogenicity island and novel lantibiotic synthesis/export
      associated genes. CONCLUSIONS: These data confirm the existence of pneumococcal
      Tn916 elements in the first decade within which pneumococcal tetracycline
      resistance was described. Furthermore, the discovery of ICESpPN1 demonstrates the
      dynamic variability of pneumococcal genetic elements and is contrasted with the
      evidence for Tn916 stability.

PMID- 23879710
TI  - The paternal perspective of the Slovenian population and its relationship with
      other populations.
AB  - BACKGROUND: The Slovenian territory is geographically positioned between the
      Alps, the Adriatic Sea, the Pannonian basin and the Dinaric Mountains and, as
      such, has served as a passageway for different populations over different periods
      of time. Turbulent historic events and the diverse geography of the region have
      produced a diverse contemporary population whose genetic analysis could provide
      insight into past demographic events. AIM: The aim of this study was to analyse Y
      chromosome biallelic and STR markers in a Slovenian population from five
      different regions. SUBJECTS AND METHODS: A total of 42 Y-chromosomal biallelic
      markers and 17 Y-STRs were genotyped in 399 individuals from five different
      Slovenian regions. RESULTS: The analysis of Y-chromosome markers revealed 29
      different haplogroups in the Slovenian population, with the most common being
      R1a1a, R1b, I2a1 and I1. Analysis of the genetic affiliations between different
      populations revealed strong affiliations of the Slovenian gene pool with West
      Slavic populations. CONCLUSION: Analysis of Y-chromosomal markers in five
      Slovenian regions revealed a diverse genetic landscape. Slovenian population
      display close genetic affiliations with West Slavic populations. The homogenous
      genetic strata of the West Slavic populations and the Slovenian population
      suggest the existence of a common ancestral Slavic population in central European
      region.

PMID- 23879711
TI  - Comparative metagenomics: natural populations of induced prophages demonstrate
      highly unique, lower diversity viral sequences.
AB  - To understand the similarities and differences between a free living viral
      population and its co-occurring temperate population, metagenomes of each type
      were prepared from the same seawater sample from Tampa Bay, FL. Libraries were
      prepared from extracted DNA of the ambient viruses and induced prophages from the
      co-occurring, viral-reduced microbial assemblage. Duplicate libraries were also
      prepared using the same DNA amplified by multiple displacement amplification. A
      non-viral-reduced, induced, amplified viral dataset from the same site in 2005
      was reanalysed for temporal comparison. The induced viral metagenome was higher
      in identifiable virus sequences and differed from the other three datasets based
      on principal component, rarefaction, trinucleotide composition and contig
      spectrum analyses. This study indicated that induced prophages are unique and
      have lower overall community diversity than ambient viral populations from the
      same site. Both of the amplified contemporary metagenomes were enriched in single
      stranded DNA (ssDNA) viral sequences. Six and 16 complete, circular ssDNA viral
      genomes were assembled from the amplified induced and ambient libraries,
      respectively, mostly similar to circoviruses. The amplified ambient metagenome
      contained genomes similar to an RNA-DNA hybrid virus recently identified in a hot
      spring and to an ssDNA virus infecting the diatom Chaetoceros. 

PMID- 23879712
TI  - Microbial asymmetric hydrolysis of 3-substituted glutaric acid diamides.
AB  - AIMS: Micro-organisms were screened for their ability to produce (R)-3-(4
      chlorophenyl) glutaric acid monoamide (CGM) from 3-(4-chlorophenyl) glutaric acid
      diamide (CGD) through stereoselective hydrolysis. (R)-CGM is a useful synthetic
      intermediate for arbaclofen. METHODS AND RESULTS: Four CGD-assimilating micro
      organisms were found to be potential catalysts for (R)-CGM production. Among
      these micro-organisms, Comamonas sp. KNK3-7 (NITE BP-963) produced (R)-CGM with
      the highest optical purity [98.7% enantiomeric excess (e.e.)] and was selected as
      the most promising strain. In addition, Comamonas sp. KNK3-7 could asymmetrically
      hydrolyse 3-isobutyl glutaric acid diamide (IBD) to produce (R)-3-isobutyl
      glutaric acid monoamide [(R)-IBM] with high optical purity (>99.0% e.e.).
      CONCLUSION: The synthesis of a (R)-3-substituted glutaric acid monoamide by
      desymmetrization of 3-substituted glutaric acid diamide with a micro-organism and
      an enzyme has not been previously reported. This finding indicates the
      possibility of the preparation of a variety of optically active 3-substituted
      glutaric acid monoamides using the amidase from Comamonas sp. KNK3-7.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The amidase from Comamonas sp. KNK3-7 may
      be useful for the chemoenzymatic synthesis of various kinds of chiral gamma
      aminobutyric acids and may be used in a 'green' process to produce gamma
      aminobutyric acids.

PMID- 23879714
TI  - Size-dependent transitions in grafted polymer brushes.
AB  - The partition function of a grafted polymer brush was calculated as a sum over
      all possible configurations, each of them being an ensemble of n1, n2, ...n(i),
      ... loops having 2, 4, ..., 2i, ... segments. A system of equations for the most
      likely configuration has been obtained, and it was concluded that no solution
      exists for an infinite chain, with nonvanishing interactions between segments and
      surface. This implies that an infinite chain is either collapsed on the surface
      (for attractive interactions) or is forming a stretched brush (for repulsive
      interactions). However, for finite chains, a solution could be found. When the
      attractive segment-surface interaction becomes sufficiently strong, the brush
      collapses on the surface (the "loops" to "trains" transition). When the
      interaction is repulsive and sufficiently strong, the brush becomes stretched,
      with most segments belonging to open loops which do not return to the surface
      (the "loops" to "tails" transition). The critical values of the segment-surface
      interaction, for which the above transitions occur, depend on the length of the
      polymer chain as well as on other physical properties of the brush, such as the
      segment-segment and segment-solvent interactions and the grafting density.

PMID- 23879715
TI  - Synthesis of acyclic ketones by catalytic, bidirectional homologation of
      formaldehyde with nonstabilized diazoalkanes. Application of a chiral
      diazomethyl(pyrrolidine) in total syntheses of erythroxylon alkaloids.
AB  - This work offers a catalytic approach to convergent ketone assembly based upon
      formal and tandem C-H insertion of diazoalkanes in the presence of limiting
      amounts of monomeric formaldehyde, which is easily generated as a gas by
      thermolysis of the inexpensive and abundant paraformaldehyde (~30 USD/kg). The
      method forms di-, tri-, and even tetrasubstituted acetones with high efficiency,
      and it has streamlined a synthesis of (-)-dihydrocuscohygrine in which the
      absolute stereochemistry of a proline-based starting material is preserved.
      Assisted by the advent of new protocols for hydrazone oxidation, we also provide
      full details on handling non-carbonyl-stabilized diazo compounds. 

PMID- 23879713
TI  - Rapid hippocampal network adaptation to recurring synchronous activity--a role
      for calcineurin.
AB  - Neuronal networks are thought to gradually adapt to altered neuronal activity
      over many hours and days. For instance, when activity is increased by suppressing
      synaptic inhibition, excitatory synaptic transmission is reduced. The underlying
      compensatory cellular and molecular mechanisms are thought to contribute in
      important ways to maintaining normal network operations. Seizures, due to their
      massive and highly synchronised discharging, probably challenge the adaptive
      properties of neurons, especially when seizures are frequent and intense - a
      condition common in early childhood. In the experiments reported here, we used
      rat and mice hippocampal slice cultures to explore the effects that recurring
      seizure-like activity has on the developing hippocampus. We found that developing
      networks adapted rapidly to recurring synchronised activity in that the duration
      of seizure-like events was reduced by 42% after 4 h of activity. At the same
      time, the frequency of spontaneous excitatory postsynaptic currents in pyramidal
      cells, the expression of biochemical biomarkers for glutamatergic synapses and
      the branching of pyramidal cell dendrites were all dramatically reduced.
      Experiments also showed that the reduction in N-methyl-D-aspartate receptor
      subunits and postsynaptic density protein 95 expression were N-methyl-D-aspartate
      receptor-dependent. To explore calcium signaling mechanisms in network
      adaptation, we tested inhibitors of calcineurin, a protein phosphatase known to
      play roles in synaptic plasticity and activity-dependent dendrite remodeling. We
      found that FK506 was able to prevent all of the electrophysiological,
      biochemical, and anatomical changes produced by synchronised network activity.
      Our results show that hippocampal pyramidal cells and their networks adapt
      rapidly to intense synchronised activity and that calcineurin play an important
      role in the underlying processes. 

PMID- 23879716
TI  - Design and implementation of the mobility assessment tool: software description.
AB  - BACKGROUND: In previous work, we described the development of an 81-item video
      animated tool for assessing mobility. In response to criticism levied during a
      pilot study of this tool, we sought to develop a new version built upon a
      flexible framework for designing and administering the instrument. RESULTS:
      Rather than constructing a self-contained software application with a hard-coded
      instrument, we designed an XML schema capable of describing a variety of
      psychometric instruments. The new version of our video-animated assessment tool
      was then defined fully within the context of a compliant XML document. Two
      software applications--one built in Java, the other in Objective-C for the Apple
      iPad--were then built that could present the instrument described in the XML
      document and collect participants' responses. Separating the instrument's
      definition from the software application implementing it allowed for rapid
      iteration and easy, reliable definition of variations. CONCLUSIONS: Defining
      instruments in a software-independent XML document simplifies the process of
      defining instruments and variations and allows a single instrument to be deployed
      on as many platforms as there are software applications capable of interpreting
      the instrument, thereby broadening the potential target audience for the
      instrument. Continued work will be done to further specify and refine this type
      of instrument specification with a focus on spurring adoption by researchers in
      gerontology and geriatric medicine.

PMID- 23879717
TI  - Cytosine arabinoside promotes cytotoxic effect of T cells on leukemia cells
      mediated by bispecific antibody.
AB  - Chemotherapeutic drugs can enhance an immune response of the host against the
      tumor in addition to killing cancer cells by direct cytotoxicity. Therefore, the
      combination of chemotherapy and immunotherapy is a promising approach for
      eliminating tumors, particularly in advanced stages. A strategic medication is to
      use a bispecific antibody format that is capable of recruiting polyclonal T cells
      around antibody-target-expressing tumor cells. Recently, we have constructed a
      bispecific antibody, anti-CD3*anti-CD19, in a diabody configuration. In this
      study, we measured B7 family members B7.1 (CD80) and B7.2 (CD86) expressed on a
      CD19(+) human leukemia cell line, Nalm-6, stimulated by cytosine arabinoside (Ara
      C). We found that a low concentration of Ara-C could upregulate CD80 expressed on
      CD19(+) Nalm-6 cells. The cytotoxicity of T lymphocytes against Nalm-6 cells in
      vitro and in vivo mediated by the anti-CD3*anti-CD19 diabody with or without a
      low dose of Ara-C was compared. The combination of the anti-CD3*anti-CD19 diabody
      and Ara-C showed the greatest effectiveness in enhancing the cytotoxicity of T
      cells against the tumor cells in vitro and in vivo. Activated T cells expressed
      higher levels of CD25 and CD69 and released more interleukin 2. Both
      perforin/granzyme B system and Fas/FasL pathway were involved in the diabody
      induced T-cell cytotoxicity. Moreover, the activated T cells could upregulate
      ICAM-3 expression on Nalm-6 cells, and inhibition of LFA-1-ICAM-3 interaction
      impaired cytotoxicity of T cells. It was noted that Ara-C could upregulate CD80
      expressed on two of five specimens of acute B lymphoblastic leukemia patient
      derived cells. Cytotoxicity of T cells against these two patient-derived cells
      was enhanced in the presence of the anti-CD3*anti-CD19 diabody. These findings
      indicate that treatment strategy using both cytotoxic lymphocyte-based
      immunotherapy and chemotherapy may have synergistic effects.

PMID- 23879718
TI  - Effects of dietary starch source on electrophysiological intestinal epithelial
      properties and intestinal glucose uptake in growing goats.
AB  - In ruminants, the potential benefit of by-pass starch to improve energy supply is
      under discussion. As efficient intestinal starch digestion and monosaccharide
      absorption are important prerequisites for an energetic benefit compared to
      ruminal fermentation, this study was conducted to characterise potential
      adaptations of intestinal tissues to different dietary starch sources
      qualitatively. The Ussing chamber technique was used to determine
      electrophysiological parameters of jejunal tissues and glucose flux rates.
      Kinetics of sodium-dependent glucose uptake into isolated brush-border membrane
      vesicles (BBMV) were calculated, and the expression level of sodium-dependent
      glucose transporter 1 (SGLT1) was determined. Samples were collected from goats
      that were assigned to three dietary treatments differing in starch content
      (hay/concentrate) and starch source (wheat/corn). Additionally, ingesta samples
      were analysed for starch and glucose contents. Jejunal tissues from hay-fed
      animals showed higher tissue conductances (G t) and numerically higher short
      circuit currents (I sc). Unidirectional glucose flux rates were higher for hay
      fed animals, whereas net flux rates were unaffected. The maximal glucose
      transport capacity into BBMV was increased for concentrate-fed animals, but the
      affinity and SGLT1 expression were not affected. Our results may indicate an
      adaptation of glucose uptake via SGLT1 to variations in dietary starch but it
      could not be excluded that intestinal uptake capacity was saturated under the
      given conditions or that the measured capacity was sufficient for absorption of
      available glucose. 

PMID- 23879719
TI  - The lid domain of the MCP hydrolase DxnB2 contributes to the reactivity toward
      recalcitrant PCB metabolites.
AB  - DxnB2 and BphD are meta-cleavage product (MCP) hydrolases that catalyze C-C bond
      hydrolysis of the biphenyl metabolite 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic
      acid (HOPDA). BphD is a bottleneck in the bacterial degradation of
      polychlorinated biphenyls (PCBs) by the Bph catabolic pathway due in part to
      inhibition by 3-Cl HOPDAs. By contrast, DxnB2 from Sphingomonas wittichii RW1
      catalyzes the hydrolysis of 3-Cl HOPDAs more efficiently. X-ray crystallographic
      studies of the catalytically inactive S105A variant of DxnB2 complexed with 3-Cl
      HOPDA revealed a binding mode in which C1 through C6 of the dienoate are
      coplanar. The chlorine substituent is accommodated by a hydrophobic pocket that
      is larger than the homologous site in BphDLB400 from Burkholderia xenovorans
      LB400. The planar binding mode observed in the crystalline complex was consistent
      with the hyper- and hypsochromically shifted absorption spectra of 3-Cl and
      3,9,11-triCl HOPDA, respectively, bound to S105A in solution. Moreover, ES(red),
      an intermediate possessing a bathochromically shifted spectrum observed in the
      turnover of HOPDA, was not detected, suggesting that substrate destabilization
      was rate-limiting in the turnover of these PCB metabolites. Interestingly,
      electron density for the first alpha-helix of the lid domain was poorly defined
      in the dimeric DxnB2 structures, unlike in the tetrameric BphDLB400. Structural
      comparison of MCP hydrolases identified the NC-loop, connecting the lid to the
      alpha/beta-hydrolase core domain, as a determinant in the oligomeric state and
      suggests its involvement in catalysis. Finally, an increased mobility of the
      DxnB2 lid may contribute to the enzyme's ability to hydrolyze PCB metabolites,
      highlighting how lid architecture contributes to substrate specificity in
      alpha/beta-hydrolases. 

PMID- 23879720
TI  - Determinants of long-term outcome in severe alcoholic hepatitis.
AB  - BACKGROUND: Although short-term outcome in severe alcoholic hepatitis (SAH) is
      well described, its long-term course remains uncharacterised. AIM: To assess
      determinants of long-term outcome in SAH. METHODS: Data were recorded from a
      cohort with SAH (admission Discriminant Function (DF) >=32). Kaplan-Meier (KM)
      and Cox proportional hazards survival analyses were performed to determine
      predictors of outcome. RESULTS: One hundred and nine patients were included;
      63.3% male, aged 49.6 +/- 9.4 years with median follow-up of 40.7 months (95% CI
      37.2-44.3). Median DF was 58, 86.2% had cirrhosis and 65.1% received
      corticosteroids and/or pentoxifylline. Overall mortality was 57.8%, 96.8% of
      deaths being liver-related and 65.1% occurring after the index hospitalisation.
      Estimated 5-year survival was 31.8%. Hepatorenal syndrome was the only baseline
      factor independently associated with mortality (HR 3.78, 95% CI 1.98-7.19, P <
      0.0001), although it predicted short-term, rather than long-term outcome (median
      survival 0.52 months, 95% CI 0.43-0.61). Of the 87 patients (79.8%) who survived
      index hospitalisation, 65.1% experienced recidivism. Abstinence at last follow-up
      remained the only independent predictor of survival in multivariate analysis (HR
      0.370, 95% CI 0.168-0.818, P = 0.014). Five-year survival was higher in
      abstainers (75.3%) compared with relapsed and continued drinkers (26.8% and
      21.0%, respectively, P = 0.005). However, the survival benefit from abstinence
      only became statistically significant at 18 months postdischarge (HR 2.714, 95%
      CI 0.995-7.404, P = 0.051). CONCLUSIONS: Estimated 5-year survival after index
      hospitalisation with SAH is 31.8% with alcohol relapse occurring in two-thirds of
      patients. Abstinence remains the only independent predictor of long-term
      survival. Novel strategies to improve abstinence after admission with SAH are
      urgently needed.

PMID- 23879721
TI  - High encapsulation efficiency of poloxamer-based injectable thermoresponsive
      hydrogels of etoposide.
AB  - CONTEXT: Hydrogels are promising polymeric network capable of sustaining the
      release of drug but have a major limitation for encapsulation of hydrophobic
      drugs. OBJECTIVE: This study was undertaken to encapsulate etoposide in poloxamer
      407-based thermosensitive hydrogels with an aim to sustain its release. MATERIALS
      AND METHODS: Etoposide-loaded hydrogels were prepared by the cold method and
      optimized for encapsulation efficiency (EE) by a 3(2) factorial design. Poloxamer
      407-poloxamer 188 hydrogel (E-P407-P188) and poloxamer 407-poly(ethylene glycol)
      (E-P407-PEG) hydrogel were characterized for SEM, swelling, sol-gel phase
      transition and injectability study. RESULTS AND DISCUSSION: In E-P407-P188
      hydrogel the EE of 75% could be obtained and in E-P407-PEG hydrogels the EE was
      84%. The SEM images showed a porous structure. The release of ETO was sustained
      up to 48 h by E-P407-PEG hydrogel and 24 h by E-P407-P188 hydrogel. The drug
      release was governed by first-order kinetics and followed Fickian diffusion
      mechanism in both the cases. CONCLUSION: Such injectable thermosensitive hydrogel
      of etoposide could be effectively used for continuous release of drug to the
      tumor and surrounding tissues.

PMID- 23879722
TI  - Effect of tobacco smoking and smoking cessation on plasma lipoproteins and
      associated major cardiovascular risk factors: a narrative review.
AB  - Cigarette smoking, active or passive, kills about 6 million people each year
      worldwide. Cardiovascular disease (CVD) is responsible for 40% of all smoking
      related deaths, lung cancer accounts for 20% of all smoking-related deaths, and
      chronic obstructive pulmonary disease is related to another 20% of deaths. In
      this narrative review we consider the relationship between cigarette smoking and
      CVD. We discuss disease states and/or CVD risk factors related to smoking, such
      as dyslipidaemia, vascular inflammation, endothelial dysfunction, arterial
      stiffness, insulin resistance, type 2 diabetes mellitus (T2DM), chronic kidney
      disease (CKD), and non-alcoholic fatty liver disease (NAFLD) as well as their
      complex interrelations. Smoking cessation can correct abnormalities related to
      smoking; however, success rates are relatively low. In cases of inability to
      quit, measures to minimize the adverse effects of smoking specifically related to
      CVD should be taken. Smokers should receive best practice treatment, according to
      guidelines, as for non-smokers.

PMID- 23879723
TI  - The Influence of the Tolerance between Mechanical Components on the Accuracy of
      Implants Inserted with a Stereolithographic Surgical Guide: A Retrospective
      Clinical Study.
AB  - BACKGROUND: The stereolithographic-guided surgery system involves a sequence of
      diagnostic and therapeutic events, and errors can arise at different stages. In
      these systems, one of the potentially clinically relevant errors may be the
      mechanical errors caused by the bur-guide gap due to the presence of a rotational
      allowance of the drills in the tubes. PURPOSE: The purpose of this retrospective
      clinical study is to determine if it is possible to reduce the total error by
      limiting the tolerance among the mechanical components and to evaluate its
      clinical incidence. MATERIALS AND METHODS: Sixty-six implants were inserted using
      the External Hex Safe(r) (Materialise Dental, Leuven, Belgium) system (Group A),
      and 71 implants were inserted using the same system with mechanical components
      modified to minimize the tolerance (Group B). Regarding only the angular
      deviation values, the t-test was used to determine the influence of reduced
      tolerance among the mechanical components on the accuracy values. RESULTS: t-Test
      showed that there is a statistically significant better accuracy with the
      modified system (Group B). CONCLUSIONS: Limiting the error that originates from
      mechanical components, total error could be statistically significantly reduced.
      Mechanical error is one of the most important source of error using External Hex
      Safe stereolithographic surgical guide.

PMID- 23879724
TI  - High-throughput screening for identification of inhibitors of EpCAM-dependent
      growth of hepatocellular carcinoma cells.
AB  - The cancer stem cell marker, EpCAM, is an important indicator of Wnt/beta-catenin
      signaling activation and a functional component of hepatocellular tumor
      initiating cells. A high-throughput screening assay was developed to identify
      inhibitors of EpCAM-dependent growth of hepatocellular carcinoma (HCC) cells.
      EpCAM(+) and EpCAM(-) HCC cell lines were assessed for differential sensitivity
      to a Wnt/beta-catenin pathway inhibitor. Libraries comprising 22 668 pure
      compounds and 107 741 crude or partially purified natural product extracts were
      tested, and 12 pure compounds and 67 natural product extracts were identified for
      further study. Three active compounds and the positive control were further
      characterized in terms of effects on EpCAM expression. Treatment of EpCAM(+)
      Hep3B cells resulted in loss of EpCAM expression as assessed by flow cytometry.
      This reduction was incomplete (most cells continued to express EpCAM), but
      resulted in generation of cell populations expressing lower levels of EpCAM.
      Sublethal concentrations (~IC50 ) reduced median EpCAM expression to 28% of
      control after 1 day and 19% of control after 2 days. Reduction in EpCAM
      expression preceded growth inhibition suggesting that a threshold of EpCAM
      expression may be required for growth of EpCAM-dependent cells. The
      identification of compounds with a variety of possible molecular targets suggests
      a likelihood of multiple mechanisms for modulation of EpCAM-dependent cell
      growth. 

PMID- 23879726
TI  - Etoricoxib-induced toxic epidermal necrolysis.

PMID- 23879725
TI  - Freeze-thaw cycles enhance decellularization of large tendons.
AB  - The use of decellularized tendon tissue as a scaffold for tendon tissue
      engineering provides great opportunities for future clinical and current research
      applications. The aim of this study was to assess the effect of repetitive freeze
      thaw cycles and two different detergents, t-octyl-phenoxypolyethoxyethanol
      (Triton X-100) and sodium dodecyl sulfate (SDS), on decellularization
      effectiveness and cytocompatibility in large tendons. Freshly collected equine
      superficial and deep digital flexor tendons were subjected to decellularization
      according to four different protocols (1 and 2: freeze-thaw cycles combined with
      either Triton X-100 or SDS; 3 and 4: Triton X-100 or SDS). Decellularization
      effectiveness was assessed based on the reduction of vital cell counts,
      histologically visible nuclei, and DNA content. Transmission electron microscopy
      was performed to evaluate cellular and extracellular matrix integrity. Further,
      cytocompatibility of scaffolds that had been decellularized according to the
      protocols including freeze-thaw cycles (protocols 1 and 2) was assessed by
      seeding the scaffolds with superparamagnetic iron oxide labeled mesenchymal
      stromal cells and monitoring the cells histologically and by magnetic resonance
      imaging for two weeks. Decellularization was significantly more effective when
      using the protocols including freeze-thaw cycles, leaving only roughly 1%
      residual nuclei and 20% residual DNA, whereas samples that had not undergone
      additional freeze-thaw cycles contained roughly 20% residual nuclei and 40%
      residual DNA. No morphological extracellular matrix alterations due to
      decellularization could be observed. Scaffolds prepared by both protocols
      including freeze-thaw cycles were cytocompatible, but the cell distribution into
      the scaffold tended to be better in scaffolds that had been decellularized using
      freeze-thaw cycles combined with Triton X-100 instead of SDS. 

PMID- 23879727
TI  - Disseminated cutaneous Ochroconis gallopava infection in an immunocompetent host:
      an unusual concurrence - a case report and review of cases reported.

PMID- 23879728
TI  - The role of adipocytokines on depressive symptoms of patients with chronic kidney
      disease.
AB  - OBJECTIVE: The aim of this study is to evaluate depression and anxiety scores
      among chronic kidney disease (CKD) patients and to search the changes of serum
      concentrations of adipokines with respect to emotional disturbances of CKD
      patients. PATIENTS AND METHODS: 150 patients recruited into this cross-sectional
      analytic study. Study groups were control, hemodialysis, predialysis, peritoneal
      dialysis and kidney transplantation groups. Fasting morning serum leptin,
      ghrelin, acylated ghrelin, neuropeptide Y, adiponectin, resistin levels of all of
      the groups were measured using ELISA (Sandwich) method. A screening interview
      based on the Structured Clinical Interview for DSM-IV and self-report scales (The
      Beck Depression [BDI] and The Beck Anxiety Inventory [BAI] and Brief Symptom
      Inventory [BSI] which is self report scales) were administered and conducted by a
      trained interviewer. RESULTS: BDI scores were significantly higher in
      hemodialysis and predialysis groups compared to control group (p = 0.009).
      Somatization sub scores of BSI were significantly higher in hemodialysis and
      peritoneal dialysis groups compared to control group (p = 0.041). Also positive
      symptom distress index scores of BSI were significantly higher in hemodialysis
      and transplantation groups compared to control group (p = 0.047). BDI score were
      significantly negatively correlated with duration of education (r = -0.165, p =
      0.045), positively correlated with presence of protein energy wasting (r = 0.198,
      p = 0.016), and resistin levels (r = 0.233, p = 0.004). CONCLUSION: CKD patients
      had higher BDI, BSI-somatization, BSI-positive symptom distress index scores
      compared to control group. High serum resistin levels, presence of protein energy
      wasting might have a role in development of depressive disorders of patients with
      chronic kidney disease.

PMID- 23879729
TI  - Lactate clearance for assessing response to resuscitation in severe sepsis.
AB  - Severe sepsis remains a major public health problem both with a high hospital
      mortality rate and with staggering associated health care expenditures. The past
      decade has seen new insights into the early resuscitation of severe sepsis and
      this is an important, controversial, and constantly changing topic to emergency
      physicians. In this article, the recent support for lactate clearance as a
      measure of early sepsis resuscitation effectiveness is summarized, lactate
      derived to oxygen-derived resuscitation variables are compared, and the
      shortcomings of lactate-derived variables are described. As summarized in this
      article, the best available experimental evidence suggests that lactate clearance
      of at least 10% at a minimum of 2 hours after resuscitation initiation is a valid
      way to assess initial response to resuscitation in severe sepsis. Associative
      data suggest that lactate normalization during resuscitation is a more powerful
      indicator of resuscitative adequacy; however, further research on the optimal
      lactate clearance parameters to use during resuscitation is needed, and many
      other important questions have yet to be answered.

PMID- 23879730
TI  - Accurate single nucleotide variant detection in viral populations by combining
      probabilistic clustering with a statistical test of strand bias.
AB  - BACKGROUND: Deep sequencing is a powerful tool for assessing viral genetic
      diversity. Such experiments harness the high coverage afforded by next generation
      sequencing protocols by treating sequencing reads as a population sample.
      Distinguishing true single nucleotide variants (SNVs) from sequencing errors
      remains challenging, however. Current protocols are characterised by high false
      positive rates, with results requiring time consuming manual checking. RESULTS:
      By statistical modelling, we show that if multiple variant sites are considered
      at once, SNVs can be called reliably from high coverage viral deep sequencing
      data at frequencies lower than the error rate of the sequencing technology, and
      that SNV calling accuracy increases as true sequence diversity within a read
      length increases. We demonstrate these findings on two control data sets, showing
      that SNV detection is more reliable on a high diversity human immunodeficiency
      virus sample as compared to a moderate diversity sample of hepatitis C virus.
      Finally, we show that in situations where probabilistic clustering retains false
      positive SNVs (for instance due to insufficient sample diversity or systematic
      errors), applying a strand bias test based on a beta-binomial model of forward
      read distribution can improve precision, with negligible cost to true positive
      recall. CONCLUSIONS: By combining probabilistic clustering (implemented in the
      program ShoRAH) with a statistical test of strand bias, SNVs may be called from
      deeply sequenced viral populations with high accuracy.

PMID- 23879731
TI  - A positive association between consanguinity and fertility in communities of
      Paraiba, Northeast Brazil.
AB  - BACKGROUND: Consanguinity of human populations can but does not have to be
      associated with increased fertility. A recent study involving communities of
      Northeast Brazil revealed increased levels of endogamy. SUBJECTS AND METHODS:
      Data from 20 451 interviewed couples and their 74 289 children were analysed.
      AIM: The present study aimed to compare fertility between consanguineous and
      unrelated couples of these communities. RESULTS: Consanguineous and unrelated
      couples of the 39 communities had an average of 4.3 (SD = 0.9) and 3.5 (SD = 0.8)
      children (p < 0.0001), respectively. Average offspring number of consanguineous
      couples varied from 3.9 (SD = 1.1) to 5.6 (SD = 3.4) for couples related at the
      level of third cousins and double first cousin/uncle-niece, respectively (p <
      0.005). The correlation coefficient between Human Development Index and fertility
      was -0.38 (p = 0.0179) and -0.23 (p = 0.17) for unrelated and related couples,
      respectively. CONCLUSION: Results indicated an overall positive association
      between consanguinity and fertility. Fertility tended to be increased, for
      closely related couples, compared to those related more distantly.

PMID- 23879732
TI  - Control of Bacillus subtilis cell shape by RodZ.
AB  - The bacterial cell wall ensures the structural integrity of the cell and is the
      main determinant of cell shape. In Bacillus subtilis, three cytoskeletal
      proteins, MreB, MreBH and Mbl, are thought to play a crucial role in maintaining
      the rod cell shape. These proteins are thought to be linked with the
      transmembrane proteins MreC, MreD and RodA, the peptidoglycan hydrolases, and the
      penicillin-binding proteins that are essential for peptidoglycan elongation.
      Recently, a well-conserved membrane protein RodZ was discovered in most Gram
      negative and Gram-positive bacteria. This protein seems to be an additional
      member of the elongation complex. Here, we examine the role of RodZ in B.
      subtilis cells. Our results indicate that RodZ is an essential protein and that
      downregulation of RodZ expression causes the formation of shorter and rounder
      cells. We also found a direct interaction between RodZ and the cytoskeletal and
      morphogenetic proteins MreB, MreBH, Mbl and MreD. Taken together, we demonstrated
      that RodZ is an important part of the cell shape determining network in B.
      subtilis. 

PMID- 23879733
TI  - A physiological and biomechanical comparison of over-ground, treadmill and
      ergometer wheelchair propulsion.
AB  - The purpose of the study was to determine which laboratory-based modality
      provides the most valid physiological and biomechanical representation of over
      ground sports wheelchair propulsion. Fifteen able-bodied participants with
      previous experience of wheelchair propulsion performed a 3-minute exercise trial
      at three speeds (4, 6 and 8 km ? h(-1)) in three testing modalities over separate
      sessions: (i) over-ground propulsion on a wooden sprung surface; (ii) wheelchair
      ergometer propulsion; (iii) treadmill propulsion at four different gradients (0%,
      0.7%, 1.0% and 1,3%). A 0.7% treadmill gradient was shown to best reflect the
      oxygen uptake (7.3 to 9.1% coefficient of variation (CV)) and heart rate
      responses (4.9 to 6.4% CV) of over-ground propulsion at 4 and 6 km ? h(-1). A
      1.0% treadmill gradient provided a more valid representation of oxygen uptake
      during over-ground propulsion at 8 km ? h(-1) (8.6% CV). Physiological demand was
      significantly underestimated in the 0% gradient and overestimated in the 1.3%
      gradient and wheelchair ergometer trials compared to over-ground trials (P<0.05).
      No laboratory-based modality provided a valid representation of the forces
      applied during OG (>= 18.4% CV). To conclude, a 0.7% treadmill gradient is
      recommended to replicate over-ground wheelchair propulsion at lower speeds (4 and
      6 km ? h(-1)) whereas a 1.0% gradient may be more suitable at 8 km ? h(-1).

PMID- 23879734
TI  - Formal lithium fixation improves direct analysis of lipids in tissue by mass
      spectrometry.
AB  - Mass spectrometry imaging is a powerful method for imaging and in situ
      characterization of lipids in thin tissue sections. Structural elucidation of
      lipids is often achieved via collision induced dissociation, and lithium-lipid
      adducts have been widely reported as providing the most structurally informative
      fragment ions. We present a method for the incorporation of lithium salts into
      tissue imaging experiments via fixation of samples in formal lithium solutions.
      The method is suitable for preparation of single tissue sections, or as an
      immersion fixation method for whole tissue blocks or organs prior to sectioning.
      We compare lithium adduct detection and MALDI-MSI of murine brain from analysis
      of tissues prepared in different ways. Tissues prepared in formal solutions
      containing lithium or sodium salts before coating in matrix via air-spray
      deposition are compared with fresh samples coated in lithium-doped matrix
      preparations by either dry-coating or air-spray deposition. Sample preparation
      via fixation in formal lithium is shown to yield the highest quality images of
      lithium adducts, resulting in acquisition of more informative product ion spectra
      in MALDI MS/MS profiling and imaging experiments. Finally, the compatibility of
      formal lithium solutions with standard histological staining protocols
      (hemotoxylin and eosin, Van Giessen and Oil Red O) is demonstrated in a study of
      human liver tissue. 

PMID- 23879735
TI  - Motivation and self-control: implicit motives moderate the exertion of self
      control in motive-related tasks.
AB  - Using a dual-task paradigm, two experiments tested whether aroused implicit
      motives would moderate the exertion of self-control in motive-related tasks. In
      Study 1, 67 participants first watched a power dialogue and were then asked to
      either enact the dialogue or simply reproduce it by writing it down. In Study 2,
      74 participants performed either the frustrating or the simple version of an
      achievement-related sensorimotor task. Participants who were high (compared to
      low) on the implicit power motive and had exerted power over another person
      subsequently showed more success at controlling their emotional responses (Study
      1). Participants who were high (compared to low) on the implicit achievement
      motive and who had mastered a frustrating sensorimotor task scored better on a
      subsequent Stroop task (Study 2). Participants in the control conditions did not
      differ in self-control performance regardless of their level of implicit motives.
      These studies provide evidence that aroused implicit motives regulate how much
      self-control is exerted when performing motive-related tasks that require self
      control. 

PMID- 23879736
TI  - Gas chromatography-mass spectrometry method for rapid identification and
      differentiation of Burkholderia pseudomallei and Burkholderia mallei from each
      other, Burkholderia thailandensis and several members of the Burkholderia cepacia
      complex.
AB  - AIMS: To develop a simple gas chromatography-mass spectrometry (GC-MS) method for
      the detection and differentiation of Burkholderia pseudomallei and Burkholderia
      mallei from each other, Burkholderia thailandensis and several members of the
      Burkholderia cepacia complex. METHODS AND RESULTS: Biomarkers were generated by
      one-step thermochemolysis (TCM) and analysed using a GC-MS system. Fragments of
      poly-3-hydroxybutyrate-co-hydroxyvalerate [poly(3HBA-co-3HVA)] produced by TCM
      were useful biomarkers. Several cellular fatty acid methyl esters were important
      in differentiating the various Burkholderia species. A statistical discrimination
      algorithm was constructed using a combination of biomarkers. The identities of
      four B. pseudomallei strains, four B. mallei strains and one strain of each near
      neighbour were confirmed in a statistically designed test using the algorithm.
      The detection limit for this method was found to be approximately 4000 cells.
      CONCLUSIONS: The method is fast, accurate and easy to use. The algorithm is
      robust against different growth conditions (medium and temperature). SIGNIFICANCE
      AND IMPACT OF THE STUDY: This assay may prove beneficial in a clinical diagnostic
      setting, where the rapid identification of B. pseudomallei is essential to
      effective treatment. This method could also be easily employed after a biological
      attack to confirm the presence of either B. pseudomallei or B. mallei.

PMID- 23879737
TI  - A questionnaire study of equine gastrointestinal parasite control in Scotland.
AB  - REASONS FOR PERFORMING STUDY: Anthelmintic resistance in equine gastrointestinal
      nematodes is a threat to equine health and welfare. Detailed knowledge of
      anthelmintic use and parasite control methods is a prerequisite to identification
      of potential risk factors for resistance. OBJECTIVES: To identify parasite
      control practices employed by equine owners in Scotland and investigate
      management factors associated with anthelmintic resistance. STUDY DESIGN:
      Questionnaire study of equine parasite control in Scotland. METHODS:
      Questionnaires were available electronically, distributed at a conference and
      mailed to clients. Key areas explored included general background, grazing
      management, anthelmintic treatment practices and use of diagnostic tests.
      RESULTS: A total of 193 responses detailing information on parasite control
      programmes of 993 equids were analysed. Moxidectin (MOX) and ivermectin or
      related combination products were the most commonly administered anthelmintics in
      the preceding 12 months. Treatments licensed for use against cyathostomin
      encysted larvae and tapeworms were administered by 80% and 90% of respondents,
      respectively. This was often achieved through indiscriminate use of MOX and MOX
      praziquantel products. Faecal egg count (FEC) analysis had been performed on 62%
      of yards and regular use of FECs reduced annual anthelmintic treatment frequency.
      Veterinarians had the greatest influence on control practices. While 40% of
      respondents believed that they practised targeted dosing, this was not associated
      with delaying treatment beyond the egg reappearance period of the anthelmintic
      used. CONCLUSIONS: Responses indicated increasing veterinary involvement and use
      of FECs. The majority of respondents administered anthelmintics licensed against
      cyathostomin encysted larvae and tapeworms. However, responses suggested that
      owners did not understand the definition of 'targeted' dosing regimens. POTENTIAL
      RELEVANCE: The high frequency of MOX use represents a potential risk factor for
      macrocyclic lactone resistance. As veterinarians were the most influential factor
      in anthelmintic choice, awareness of macrocyclic lactone resistance and potential
      risk factors for its development and spread should be incorporated into client
      advice.

PMID- 23879738
TI  - Polyglycolic acid-polylactic acid scaffold response to different progenitor cell
      in vitro cultures: a demonstrative and comparative X-ray synchrotron radiation
      phase-contrast microtomography study.
AB  - Spatiotemporal interactions play important roles in tissue development and
      function, especially in stem cell-seeded bioscaffolds. Cells interact with the
      surface of bioscaffold polymers and influence material-driven control of cell
      differentiation. In vitro cultures of different human progenitor cells, that is,
      endothelial colony-forming cells (ECFCs) from a healthy control and a patient
      with Kaposi sarcoma (an angioproliferative disease) and human CD133+ muscle
      derived stem cells (MSH 133+ cells), were seeded onto polyglycolic acid
      polylactic acid scaffolds. Three-dimensional (3D) images were obtained by X-ray
      phase-contrast microtomography (micro-CT) and processed with the Modified
      Bronnikov Algorithm. The method enabled high spatial resolution detection of the
      3D structural organization of cells on the bioscaffold and evaluation of the way
      and rate at which cells modified the construct at different time points from
      seeding. The different cell types displayed significant differences in the
      proliferation rate. In conclusion, X-ray synchrotron radiation phase-contrast
      micro-CT analysis proved to be a useful and sensitive tool to investigate the
      spatiotemporal pattern of progenitor cell organization on a bioscaffold. 

PMID- 23879739
TI  - Cost of illness of the stomach cancer in Japan - a time trend and future
      projections.
AB  - BACKGROUND: Stomach cancer is one of the leading causes of cancer deaths in
      Japan. The objectives of this study were to estimate and project the economic
      burden associated with stomach cancer in Japan, and to identify the key factors
      that drive the economic burden of stomach cancer. METHODS: We calculated Cost of
      illness (COI) of 1996, 2002, 2008, 2014 and 2020 by using government office
      statistics and the COI method. We calculated direct cost and indirect cost
      (morbidity cost and mortality cost), and estimated the COI by summing them up.
      RESULTS: The number of deaths remained at approximately 50,000 in 1996-2008. COI
      was in downward trend from 1,293.5 billion yen in 1996 to 1,114.2 billion yen in
      2008. Morbidity cost was 85.6 billion yen and 54.0 billion yen, mortality cost
      was 972.3 billion yen and 806.4 billion yen, and mortality cost per person was
      19.4 million yen and 16.1 million yen in 1996 and 2008, respectively. Decrease of
      mortality cost that accounted for a large part of the COI (72.4% in 2008) was the
      major contributing factor. COI is predicted to decrease if the trend of health
      related indicators continues (442.8-1,056.1 billion yen depending on the model in
      2020). Mortality cost per person is also predicted to decrease (9.5-12.5 million
      yen depending on the model in 2020). CONCLUSIONS: If the trend of health related
      indicators continues, it is estimated that COI of stomach cancer would decrease.
      "Aging", "change of the healthcare providing system" and "new medical technology"
      are considered as contributing factors of COI.

PMID- 23879740
TI  - Helicobacter pylori infection associated with high HbA1c and type 2 diabetes.
AB  - BACKGROUND: Although the association between chronic Helicobacter pylori
      infection and type 2 diabetes has been suggested, findings have been
      inconsistent. This study evaluated the association between chronic H. pylori
      infection and glucose regulation. MATERIALS AND METHODS: We evaluated H. pylori
      infection status of participants recruited from the gastroenterology clinic at
      our hospital. At baseline, we performed blood tests including fasting plasma
      glucose, insulin, glycated haemoglobin A1c (HbA1c) and other biochemical
      measurements. Insulin resistance and beta-cell function were assessed by
      homoeostasis model assessment (HOMA-IR and HOMA-B, respectively). RESULTS: A
      total of 2070 participants were recruited. Those who had H. pylori infections had
      higher serum HbA1c levels and lower HOMA-B than those who did not (5.78% vs.
      5.69%, P = 0.01 and 53.85 + 38.43 vs. 60.64 + 43.40, P = 0.009, respectively).
      They also had a significantly higher prevalence of type 2 diabetes (8.97% vs.
      5.57%, P= 0.02). Chronic H. pylori infection was significantly associated with
      high levels of HbA1c and type 2 diabetes in participants above 65 years old (P =
      0.001) and decreased insulin secretion and sensitivity in those under 45 years (P
      = 0.05). CONCLUSIONS: Long-term H. pylori infection is significantly associated
      with high levels of HbA1c and decreased insulin secretion in this Chinese
      population. Proper screening for H. pylori infection combined with regular
      monitoring of blood glucose and HbA1c levels might be effective for the early
      detection of glucose dysregulation and prevention of type 2 diabetes.

PMID- 23879742
TI  - Assessment of auditory processing disorder in children using an adaptive filtered
      speech test.
AB  - OBJECTIVE: One type of test commonly used to assess auditory processing disorder
      (APD) is the 'filtered words test' (FWT), in which a monaural, low-redundancy
      speech sample is distorted by using filtering to modify its frequency content.
      One limitation of the various existing FWTs is that they are performed using a
      constant level of low-pass filtering, making them prone to ceiling and floor
      effects that compromise their efficiency and accuracy. A recently developed
      computer-based test, the University of Canterbury Adaptive Speech Test- Filtered
      Words (UCAST-FW), uses an adaptive procedure intended to improve the efficiency
      and sensitivity of the test over its constant-level counterparts. DESIGN: The
      UCAST-FW was administered to school-aged children to investigate the ability of
      the test to distinguish between children with and without APD. STUDY SAMPLE:
      Fifteen children aged 7-13 diagnosed with APD, and an aged-matched control group
      of 10 children with no history of listening difficulties. RESULTS: Data obtained
      demonstrates a significant difference between the UCAST-FW results obtained by
      children with APD and those with normal auditory processing. CONCLUSIONS: These
      findings provide evidence that the UCAST-FW may discriminate between children
      with and without APD with greater sensitivity than its constant-level
      counterparts.

PMID- 23879741
TI  - Implementation of alternative test strategies for the safety assessment of
      engineered nanomaterials.
AB  - Nanotechnology introduces a new field that requires novel approaches and methods
      for hazard and risk assessment. For an appropriate scientific platform for safety
      assessment, nanoscale properties and functions of engineered nanomaterials
      (ENMs), including how the physicochemical properties of the materials relate to
      mechanisms of injury at the nano-bio interface, must be considered. Moreover,
      this rapidly advancing new field requires novel test strategies that allow
      multiple toxicants to be screened in robust, mechanism-based assays in which the
      bulk of the investigation can be carried out at the cellular and biomolecular
      level whilst maintaining limited animal use and is based on the contribution of
      toxicological pathways to the pathophysiology of disease. First, a predictive
      toxicological approach for the safety assessment of ENMs will be discussed
      against the background of a '21st-century vision' for using alternative test
      strategies (ATSs) to perform toxicological assessment of large numbers of
      untested chemicals, thereby reducing a backlog that could otherwise become a
      problem for nanotechnology. An ATS is defined here as an alternative to animal
      experiments or refinement/reduction alternative to traditional animal testing.
      Secondly, the approach of selecting pathways of toxicity to screen for the
      pulmonary hazard potential of carbon nanotubes and metal oxides will be
      discussed, as well as how to use these pathways to perform high-content or high
      throughput testing and how the data can be used for hazard ranking, risk
      assessment, regulatory decision-making and 'safer-by-design' strategies. Finally,
      the utility and disadvantages of this predictive toxicological approach to ENM
      safety assessment, and how it can assist the 21st-century vision, will be
      addressed. 

PMID- 23879743
TI  - 3-Phosphoglycerate is an allosteric activator of pyruvate kinase from the
      hyperthermophilic archaeon Pyrobaculum aerophilum.
AB  - Pyruvate kinase (PK) is a highly regulated enzyme that catalyzes the final step
      of glycolysis. PK from the hyperthermophilic archaeon Pyrobaculum aerophilum
      (PaPK) is distinguished from most PK enzymes of eukarya and bacteria by not
      responding to any known allosteric effectors and apparently exhibiting only
      cooperative regulation. We determined the crystal structure of PaPK to 2.2 A
      resolution and, in a manner consistent with the lack of a response to
      conventional effectors, observed that the canonical allosteric site is occluded
      by a tyrosine. Unexpectedly, though, a bound sulfate was observed at a position
      equivalent to the 6'-phosphate of sugar effectors, suggesting an allosteric site,
      but for an unknown effector and sharing only the phosphate position. A search of
      three-carbon intermediates of glycolysis revealed 3-phosphoglycerate (3PG) as a
      potent allosteric activator of PaPK. The response was abolished by mutation of
      residues that contact the sulfate and of an arginine proposed to interact with
      the 3PG carboxylate group. Regulation of PK by 3PG is consistent with the
      ancestral glycolysis of hyperthermophilic archaea in which this intermediate is
      produced by an irreversible enzyme, glyceraldehyde 3-phosphate ferredoxin
      oxidoreductase. Coordinated regulation within the lower half of glycolysis
      contrasts sharply with conventional glycolysis in which 3PG is produced
      reversibly and PK is regulated by fructose 1,6-bisphosphate, the product of
      phosphofructokinase, an irreversible enzyme in the upper half of the pathway.
      Regulation of PaPK by a carboxylate molecule rather than a sugar phosphate may
      reflect a step in the evolution of glycolysis that predates the dominance of
      sugars in metabolism. 

PMID- 23879745
TI  - Did recent world record marathon runners employ optimal pacing strategies?
AB  - We apply statistical analysis of high frequency (1 km) split data for the most
      recent two world-record marathon runs: Run 1 (2:03:59, 28 September 2008) and Run
      2 (2:03:38, 25 September 2011). Based on studies in the endurance cycling
      literature, we develop two principles to approximate 'optimal' pacing in the
      field marathon. By utilising GPS and weather data, we test, and then de-trend,
      for each athlete's field response to gradient and headwind on course, recovering
      standardised proxies for power-based pacing traces. The resultant traces were
      analysed to ascertain if either runner followed optimal pacing principles; and
      characterise any deviations from optimality. Whereas gradient was insignificant,
      headwind was a significant factor in running speed variability for both runners,
      with Runner 2 targeting the (optimal) parallel variation principle, whilst Runner
      1 did not. After adjusting for these responses, neither runner followed the
      (optimal) 'even' power pacing principle, with Runner 2's macro-pacing strategy
      fitting a sinusoidal oscillator with exponentially expanding envelope whilst
      Runner 1 followed a U-shaped, quadratic form. The study suggests that: (a) better
      pacing strategy could provide elite marathon runners with an economical pathway
      to significant performance improvements at world-record level; and (b) the data
      and analysis herein is consistent with a complex-adaptive model of power
      regulation.

PMID- 23879744
TI  - Detection of phase-dependent transcriptomic changes and Rubisco-mediated CO2
      fixation into poly (3-hydroxybutyrate) under heterotrophic condition in Ralstonia
      eutropha H16 based on RNA-seq and gene deletion analyses.
AB  - BACKGROUND: Ralstonia eutropha H16 is well known to produce polyhydroxyalkanoates
      (PHAs), which are potential bio-based biodegradable plastics, in an efficient
      manner as an energy storage material under unbalanced growth conditions. To
      obtain further knowledge of PHA biosynthesis, this study performed a quantitative
      transcriptome analysis based on deep sequencing of the complementary DNA
      generated from the RNA (RNA-seq) of R. eutropha H16. RESULTS: Total RNAs were
      extracted from R. eutropha cells in growth, PHA production, and stationary phases
      on fructose. rRNAs in the preparation were removed by repeated treatments with
      magnetic beads specific to bacterial rRNAs, and then the 36 bp sequences were
      determined using an Illumina high-throughput sequencer. The RNA-seq results
      indicated the induction of gene expression for transcription, translation, cell
      division, peptidoglycan biosynthesis, pilus and flagella assembly, energy
      conservation, and fatty acid biosynthesis in the growth phase; and the repression
      trends of genes involved in central metabolisms in the PHA production phase.
      Interestingly, the transcription of genes for Calvin-Benson-Bassham (CBB) cycle
      and several genes for beta-oxidation were significantly induced in the PHA
      production phase even when the cells were grown on fructose. Moreover,
      incorporation of 13C was observed in poly(3-hydroxybutyrate) synthesized by R.
      eutropha H16 from fructose in the presence of NaH13CO3, and further gene deletion
      analyses revealed that both of the two ribulose 1,5-bisphosphate carboxylase
      (Rubiscos) in CBB cycle were actually functional in CO2 fixation under the
      heterotrophic condition. CONCLUSIONS: The results revealed the phase-dependent
      transcriptomic changes and a CO2 fixation capability under heterotrophic
      conditions by PHA-producing R. eutropha.

PMID- 23879746
TI  - Structure characterization and immunocompetence of a glucan from the fruiting
      bodies of Cantharellus cibarius.
AB  - A protein-bound polysaccharide fraction (JBP-1) was obtained from the fruiting
      bodies of Cantharellus cibarius. Its chemical composition was studied by the
      cooperative usage of multiple chemical and spectral methods and characterized to
      be a fraction with a molecular weight of 4.8 * 10(5) Da and only composed of
      glucose. Methylation analysis revealed that the sugar residues in JBP-1 are
      existing as t-, 1,6-, and 1,3,6-linked Glcp sugar residues. The immunocompetence
      of the fraction was evaluated with the proliferation assay of mouse splenocytes,
      and the result revealed that JBP-1 could significantly stimulate the
      proliferation of mouse splenocytes in a dose-dependent manner, with p < 0.001 at
      the concentration of 100 MUg/ml and 30 MUg/ml, p < 0.05 at 10 MUg/ml. These
      results give us a primary scientific evidence to further explore the
      pharmaceutical function of this mushroom.

PMID- 23879747
TI  - The burden of stroke and priorities for stroke research.

PMID- 23879748
TI  - Setting priorities for stroke care and research.
AB  - Recent publications describing the sobering global increase in stroke mortality
      and global life years lost due to stroke despite improvements in developed
      countries have drawn focus on the severe impact of stroke in the developing
      world. At the same time, three recent interventional trials that failed to
      demonstrate an important role for catheter-based therapies in acute stroke have
      called into question this expensive use of technology. Coupling all of this new
      data leads to the natural conclusion that a focus on stroke prevention for the
      developing world, and for the poor in developed countries, should be where we set
      our priorities for the foreseeable future. 

PMID- 23879749
TI  - Life after stroke - is palliative care relevant? A better understanding of
      illness trajectories after stroke may help clinicians identify patients for a
      palliative approach to care.
AB  - Only about 50% of people who have a stroke survive to five-years. Clinicians
      should identify those most at risk of dying, and gradually integrate palliative
      care. Such holistic and anticipatory care will be of benefit to patients and
      their family carers; should reduce futile treatments, medications, or
      unsuccessful resuscitation attempts; and help more people die how and where they
      choose. Research is exploring how best to provide palliative and end-of-life care
      in acute stroke units, but how best to improve holistic, ongoing care in the
      community is poorly understood. The concept of fluctuating illness trajectories
      might help clinicians meet the multidimensional needs of stroke survivors at
      different time points. 'Illness trajectory' research in cancer has suggested that
      social decline mirrors the physical decline, while psychological and existential
      distress tended to be most acute at diagnosis, returning home after treatment,
      disease recurrence, and in the last days. Further research is needed to explore
      how best to provide palliative care at different stages of the 'stroke journey',
      and the nature of illness trajectories after stroke. 

PMID- 23879750
TI  - Endogenous neuroprotection: hamartin modulates an austere approach to staying
      alive in a recession.
AB  - Tuberous sclerosis complex 1 (hamartin) is an effective endogenous
      neuroprotectant. Understanding the endogenous mechanism for neuroprotection
      mediated by hamartin may afford a novel approach to effective treatment of
      neurological diseases such as stroke, neurodegenerative diseases, and epilepsy,
      with possible applications to nonneurological conditions. 

PMID- 23879751
TI  - A systematic review of the benefits of mindfulness-based interventions following
      transient ischemic attack and stroke.
AB  - BACKGROUND: Recent epidemiological studies have demonstrated an association
      between perceived psychological stress and ischemic stroke. A feature of stroke
      is recurrence; 30-40% within five-years following first transient ischemic
      attack/stroke. Equipping patients with skills and coping strategies to help
      reduce or manage perceived psychological stress may represent an important
      secondary prevention intervention. Mindfulness-based interventions are
      structured, group-based self-management programmes with potential to help people
      with long-term conditions cope better with physical, psychological, or emotional
      distress. Review evidence suggests significant benefits across a range of
      physical and mental health problems. However, we could find no evidence synthesis
      relating specifically to the benefits of mindfulness-based interventions
      following transient ischemic attack/stroke. AIM: The review aims to evaluate the
      benefits of mindfulness-based interventions following transient ischemic
      attack/stroke. METHODS: Six major databases were searched using subject headings
      and key words. Papers were screened using review-specific criteria. Critical
      appraisal and data extraction were conducted independently by two reviewers.
      Statistical meta-analysis was not possible; therefore findings are presented in
      narrative form. RESULTS: Four studies involving 160 participants were reviewed.
      Three papers reported mindfulness-based interventions delivered to groups; one
      paper reported a mindfulness-based intervention which was delivered one to one.
      The results demonstrate a positive trend in favor of the benefits of mindfulness
      based interventions across a range of psychological, physiological, and
      psychosocial outcomes including anxiety, depression, mental fatigue, blood
      pressure, perceived health, and quality of life. No evidence of harm was found.
      CONCLUSION: Following transient ischemic attack/stroke, people may derive a range
      of benefits from mindfulness-based interventions; however, further
      methodologically robust trials are required.

PMID- 23879753
TI  - Early carotid artery endarterectomy after intravenous thrombolysis therapy.

PMID- 23879754
TI  - Early engagement in exercise improves coronary artery disease risk in newly
      diagnosed transient ischemic attack patients.

PMID- 23879752
TI  - Platelet-oriented inhibition in new TIA and minor ischemic stroke (POINT) trial:
      rationale and design.
AB  - BACKGROUND: Ischemic stroke and other vascular outcomes occur in 10-20% of
      patients in the three-months following a transient ischemic attack or minor
      ischemic stroke, and many are disabling. The highest risk period for these
      outcomes is the early hours and days immediately following the ischemic event.
      Aspirin is the most common antithrombotic treatment used for these patients. AIM:
      The aim of POINT is to determine whether clopidogrel plus aspirin taken <12 h
      after transient ischemic attack or minor ischemic stroke symptom onset is more
      effective in preventing major ischemic vascular events at 90 days in the high
      risk, and acceptably safe, compared with aspirin alone. DESIGN: POINT is a
      prospective, randomized, double-blind, multicenter trial in patients with
      transient ischemic attack or minor ischemic stroke. Subjects are randomized to
      clopidogrel (600 mg loading dose followed by 75 mg/day) or matching placebo, and
      all will receive open-label aspirin 50-325 mg/day, with a dose of 162 mg daily
      for five-days followed by 81 mg daily strongly recommended. STUDY OUTCOMES: The
      primary efficacy outcome is the composite of new ischemic vascular events -
      ischemic stroke, myocardial infarction, or ischemic vascular death - by 90 days.
      The primary safety outcome is major hemorrhage, which includes symptomatic
      intracranial hemorrhage. DISCUSSION: Aspirin is the most common antithrombotic
      given to patients with a stroke or transient ischemic attack, as it reduces the
      risk of subsequent stroke. This trial expects to determine whether more
      aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated
      acutely, is more effective than aspirin alone.

PMID- 23879755
TI  - Stroke and cancer: misfortunes never come singularly.

PMID- 23879756
TI  - Prevalence of carotid artery stenosis in southern China: a retrospective, cross
      sectional study.

PMID- 23879757
TI  - Tissue rather than time-based thrombolysis in stroke.

PMID- 23879758
TI  - Erythropoietin and the 15 cities young stroke study.

PMID- 23879759
TI  - ACTA2 is not a major responsible gene for spontaneous cerebral artery dissection.

PMID- 23879760
TI  - Relation between red blood cell distribution width and ischemic stroke: a case
      control study.

PMID- 23879761
TI  - The potential of motion quantification systems in the automatic evaluation of
      motor function after stroke.

PMID- 23879762
TI  - Anti-accreditation for stroke management in Taiwan.

PMID- 23879763
TI  - Paraoxonase genes and the susceptibilty to ischemic stroke.

PMID- 23879764
TI  - Transcranial magnetic stimulation predicts functional recovery after botulinum
      toxin treatment in stroke patients.

PMID- 23879765
TI  - The impact of demographic and logistic factors on effectiveness and safety of IV
      thrombolysis in patients with acute ischemic stroke in a rural hospital in
      southeastern Poland.

PMID- 23879767
TI  - The significance of professional roles in collaboration on patients' transitions
      from hospital to home via an intermediate unit.
AB  - The increasing complexity of the healthcare system and of patients' conditions,
      as well as resource limitations, calls for collaboration between professionals
      and institutions. The objective of this study was to explore the significance of
      professional roles in collaboration on patients' transitions from hospital to
      home via an intermediate care unit. We studied collaboration in the intermediate
      unit and between healthcare providers in the unit, a hospital and four
      municipalities in the hospital catchment area. Data were drawn from interviews
      with thirty-eight healthcare providers within specialist and primary health care
      and from observations in six multidisciplinary meetings, six report meetings and
      four discharge meetings in the unit. Transcripts of interviews and observations
      were analysed using a method of systematic text condensation. The results show
      that collaboration inside the intermediate unit and between the healthcare
      institutions was primarily 'a nursing matter'. Collaboration among the nurses was
      generally good. Except for the physician, all the healthcare providers
      experienced the collaboration in the unit as unidisciplinary rather than
      interprofessional. Although they wanted to collaborate interprofessionally, they
      were unable to do so in practice. The unit's physiotherapists and occupational
      therapists found themselves to be excluded from the nurses' community of
      practice, while the physician experienced the collaboration as excellent. The
      findings indicate that healthcare providers have different understandings of
      interprofessional collaboration and that in certain situations, they consider
      interprofessional collaboration to be an inappropriate working method.
      Interprofessional collaboration can promote a learning environment among
      healthcare providers. To achieve better interprofessional collaboration, it is
      probably necessary to create mutual understandings of interprofessionality and to
      reach an agreement on the situations in which it is an appropriate way to work. 

PMID- 23879766
TI  - Is orbital volume associated with eyeball and visual cortex volume in humans?
AB  - BACKGROUND: In humans orbital volume increases linearly with absolute latitude.
      Scaling across mammals between visual system components suggests that these
      larger orbits should translate into larger eyes and visual cortices in high
      latitude humans. Larger eyes at high latitudes may be required to maintain
      adequate visual acuity and enhance visual sensitivity under lower light levels.
      AIM: To test the assumption that orbital volume can accurately index eyeball and
      visual cortex volumes specifically in humans. SUBJECTS AND METHODS: Structural
      Magnetic Resonance Imaging (MRI) techniques are employed to measure eye and orbit
      (n = 88) and brain and visual cortex (n = 99) volumes in living humans. Facial
      dimensions and foramen magnum area (a proxy for body mass) were also measured.
      RESULTS: A significant positive linear relationship was found between (i) orbital
      and eyeball volumes, (ii) eyeball and visual cortex grey matter volumes and (iii)
      different visual cortical areas, independently of overall brain volume.
      CONCLUSION: In humans the components of the visual system scale from orbit to eye
      to visual cortex volume independently of overall brain size. These findings
      indicate that orbit volume can index eye and visual cortex volume in humans,
      suggesting that larger high latitude orbits do translate into larger visual
      cortices.

PMID- 23879768
TI  - The use of a new indirect method to estimate ethnic-group fertility rates for
      subnational projections for England.
AB  - To project the ethnic-group populations of local authorities in England to 2051,
      estimates of ethnic-specific fertility rates were needed. In the absence of
      ethnic information on birth records, we developed indirect estimation methods
      that use a combination of vital statistics, the census (both microdata and
      aggregate tables), and survey data (Labour Force Survey). We estimated age
      specific and total fertility rates successively for five broad ethnic groups
      encompassed by all data-sets, and for eight ethnic groups encompassed by the 1991
      and 2001 Censuses for England. We then used census data to disaggregate the
      estimates to the 16 ethnic groups required for the subnational projections and
      the Hadwiger function to estimate single-year-of-age estimates. We estimated the
      uncertainty around the fertility estimates and used a logistic model to project
      rates to 2021, after which we assumed rates would remain constant. 

PMID- 23879769
TI  - Itchy dermatoses in Iraqi children: a single hospital experience.

PMID- 23879771
TI  - Correlation between the bone density recorded by a computerized implant motor and
      by a histomorphometric analysis: a preliminary in vitro study on bovine ribs.
AB  - PURPOSE: The purpose of the present preliminary in vitro study on bovine ribs was
      to validate a new intraoperative site-specific classification of bone Density
      Index (IDI), obtained by an innovative computerized implant motor, by correlating
      these data with the data obtained by the histomorphometrical evaluation of the
      same samples. MATERIALS AND METHODS: Five segments of bovine ribs were used, and
      a total of 22 perforations were performed. A computerized implant motor ("Torque
      Measuring Motor") was used to evaluate the bone density, which was classified
      into four classes: ID1, ID2, ID3, and ID4. Histomorphometrical analysis of bone
      density, expressed as percentage of bony trabeculae over the total biopsy area,
      was also performed. The data of bone density obtained by the implant motor were
      statistically correlated with the histomorphometrical results. RESULTS: A
      significant positive correlation was found between the bone density measured by
      the implant motor and the bone density assessed by histomorphometry (r = 0.89, p
      < .0001). Moreover, a significant positive correlation in D1, D2, and D4, whereas
      a negative, not significant correlation in D3 was found. CONCLUSION: Within the
      limitations of this in vitro study, the intraoperative site-specific
      classification of bone density, obtained with this innovative system, could be
      helpful for the clinician to tailor the surgical protocol to the different
      situations in implant dentistry.

PMID- 23879770
TI  - Diversity and distribution of a key sulpholipid biosynthetic gene in marine
      microbial assemblages.
AB  - Sulphoquinovosyldiacylglycerols (SQDG) are polar sulphur-containing membrane
      lipids, whose presence has been related to a microbial strategy to adapt to
      phosphate deprivation. In this study, we have targeted the sqdB gene coding the
      uridine 5'-diphosphate-sulphoquinovose (UDP-SQ) synthase involved in the SQDG
      biosynthetic pathway to assess potential microbial sources of SQDGs in the marine
      environment. The phylogeny of the sqdB-coding protein reveals two distinct
      clusters: one including green algae, higher plants and cyanobacteria, and another
      one comprising mainly non-photosynthetic bacteria, as well as other cyanobacteria
      and algal groups. Evolutionary analysis suggests that the appearance of UDP-SQ
      synthase occurred twice in cyanobacterial evolution, and one of those branches
      led to the diversification of the protein in members of the phylum
      Proteobacteria. A search of homologues of sqdB-proteins in marine metagenomes
      strongly suggested the presence of heterotrophic bacteria potential SQDG
      producers. Application of newly developed sqdB gene primers in the marine
      environment revealed a high diversity of sequences affiliated to cyanobacteria
      and Proteobacteria in microbial mats, while in North Sea surface water, most of
      the detected sqdB genes were attributed to the cyanobacterium Synechococcus sp.
      Lipid analysis revealed that specific SQDGs were characteristic of microbial mat
      depth, suggesting that SQDG lipids are associated with specific producers. 

PMID- 23879772
TI  - Delayed telephone consent in emergency medicine research.

PMID- 23879774
TI  - Interaction between glutathione S-transferase variants, maternal smoking and
      childhood wheezing changes with age.
AB  - BACKGROUND: Maternal smoking increases the risk of respiratory symptoms in
      children. Glutathione S-transferases (GSTs) detoxify xenobiotics from tobacco
      smoke, and functional polymorphism in GST gene(s) could predispose children to
      the detrimental effects of maternal smoking. Our objective was to investigate
      interactions between GST variants and maternal smoking in relation to the
      development of wheezing during childhood and whether any such interaction changes
      with time. METHODS: In a population-based birth cohort, we assessed maternal
      smoking and current wheeze at five time points during the first 11 yr of life.
      DNA was genotyped for GSTP1, GSTM1 and GSTT1 (n = 807). Longitudinal analyses
      were performed using generalized estimating equations. RESULTS: During early
      childhood, children whose mothers smoked were more likely to wheeze, with the
      strongest association observed at age 3 yr (p = 0.006). In a longitudinal model,
      children with GSTP1 AA and AG genotypes had significantly higher risk of wheeze
      compared with GG homozygotes. We observed a significant interaction between GSTP1
      and maternal smoking where the risk of infantile wheezing was significantly
      increased in AA homozygotes, but only if their mothers smoked (OR 2.59, [1.08
      6.21], p(int) = 0.03). Furthermore, amongst AA carriers, there was a significant
      interaction between child's age and maternal smoking, with the effect of maternal
      smoking on the risk of wheeze significantly diminishing with age (p(int) = 0.05);
      no such findings were observed for GSTM1 and GSTT1. CONCLUSIONS: Children with AA
      genotype for GSTP1 are at increased risk of early-life wheezing if their mothers
      smoke, but the effect of maternal smoking on wheezing diminishes with time.

PMID- 23879775
TI  - Self-reported problems and wishes for plastic surgery after bariatric surgery.
AB  - In the affluent part of the world, there is an increasing occurrence of obesity
      with Body Mass Index (BMI) above 40, which has resulted in an increasing number
      of operations such as gastric bypass (GB). After massive weight loss there will
      often be a need for subsequent plastic surgical correction, since some of the
      patients will experience problems due to excess skin. Foreign studies estimate
      that ~30% of all bariatric surgery patients will at some point seek plastic
      surgical correction of excess skin. The aim of this study is to investigate to
      what extent the GB patients themselves consider plastic surgery for removal of
      excess skin, and their reasons and motivations for this. The investigation was
      performed as an anonymous questionnaire handed out to 150 patients at the 1-year
      standard consultation for GB patients at a private hospital. The questionnaire
      contained information about demographic data, patient habits, earlier or present
      comorbidity, physical problems, psychological problems, and cosmetic problems due
      to excess skin. Also, it contained information about what anatomical area
      bothered the patient the most. One hundred and thirty-eight patients responded to
      the questionnaire, and the investigation showed that 89.9% of the patients had a
      wish for plastic surgery for several different reasons. This patient demand
      showed to have no correlation to age, gender, smoking habits, or earlier
      comorbidity.

PMID- 23879776
TI  - Histopathologic findings in breast reduction specimens.
AB  - Reduction mammaplasty is a commonly performed operation for treatment of breast
      hypertrophy. It allows examination of specimens from a seemingly healthy
      population. Although there are many publications reporting the incidence of
      occult breast carcinomas, only a few studies have specifically examined the
      incidence of other breast lesions in reduction mammaplasty specimens. The authors
      conducted a single-centre retrospective chart review examining the incidence of
      benign and precancerous lesions in breast reduction specimens. Both age and the
      number of tissue sections were evaluated for the association with important
      pathologic findings. Of the 95 patients who underwent reduction mammaplasty,
      eight patients (8.4%) had atypical lesions. Fourteen patients (15%) had
      proliferative and 54 patients (57%) had non-proliferative breast lesions. No
      occult invasive breast cancer was identified in the breast reduction specimens.
      The existence of significant pathologic findings was not associated with age (p =
      0.231, student t-test). On the other hand, it was found to be associated with the
      number of tissue sections (p = 0.046, Mann-Whitney U-test). This study reveals
      that breast reduction specimens should be analyzed histologically since a
      considerable amount of patients have breast lesions with increased cancer risk.
      Therefore, this analysis would guide the management of these patients in the
      follow-up period.

PMID- 23879777
TI  - Isolation, characterization, and hepatoprotective effects of the raffinose family
      oligosaccharides from Rehmannia glutinosa Libosch.
AB  - This study was aimed to isolate and characterize the raffinose family
      oligosaccharides (RGOs) from a novel plant source of Rehmannia glutinosa Libosch,
      and further evaluate whether RGOs can attenuate CCl4-induced oxidative stress and
      hepatopathy in mice. HPLC analysis showed that RGOs were mainly composed of
      stachyose (61.7%, w/w), followed by 23.7% raffinose and 7.1% sucrose.
      Administration of RGOs orally daily in mice for 21 days significantly reduced the
      impact of CCl4 toxicity on the serum markers of liver damage, serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total-cholesterol (TC),
      and triglycerides (TG). RGOs also increased antioxidant levels of hepatic
      glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD),
      and total antioxidant capacity (T-AOC), and ameliorated the elevated hepatic
      formation of malonaldehyde (MDA) induced by CCl4 in mice, which coincided with
      the histological alteration. These findings exhibited the potential prospect of
      RGOs as functional ingredients to prevent ROS-related liver damage. 

PMID- 23879778
TI  - Relationship between eating behaviors and physical activity among primary and
      secondary school students: results of a cross-sectional study.
AB  - BACKGROUND: With a view toward developing concerted efforts in fostering healthy
      eating habits and a physically active lifestyle among young people, a study was
      carried out to explore associations between eating behavior and physical activity
      (PA). METHODS: In the school district, questionnaires were completed at home by
      parents of primary school children (N = 8612) and by secondary school youth (N =
      5250) during a break in the schedule. The rates of response were 79% and 83%,
      respectively. Inferential and descriptive analyses were performed. RESULTS: The
      results indicate significant differences between the eating behaviors of young
      people who engage in 60 minutes of daily PA and those who are sedentary. The
      physically active children were generally more likely to eat fruit, vegetables,
      and whole-grain products and to have breakfast (p < .05 among high-school
      students). The lack of self-confidence (55%) and not enjoying PA (46%) stood out
      as the greatest obstacles facing adolescents trying to lose weight. CONCLUSION:
      There should be particular actions targeting students in the last half of primary
      school aimed at developing individual accountability and autonomy with respect to
      healthy eating and PA. These actions should also consider sex differences and
      those who have more sedentary lifestyles.

PMID- 23879779
TI  - Healthy BuddiesTM reduces body mass index z-score and waist circumference in
      Aboriginal children living in remote coastal communities.
AB  - BACKGROUND: Aboriginal children are at increased risk for obesity and type 2
      diabetes. Healthy BuddiesTM-First Nations (HB) is a curriculum-based, peer-led
      program promoting healthy eating, physical activity, and self-esteem. METHODS:
      Although originally designed as a pilot pre-/post-analysis of 3 remote Aboriginal
      schools that requested and received HB training, one school did not implement the
      program and was used as a control group. Outcomes included changes in body mass
      index z-score (zBMI), waist circumference (WC), blood pressure (BP), self-esteem,
      health behavior, and knowledge over 1 school year in kindergarten to grade 12
      children. RESULTS: There was a significant decrease in zBMI (1.10 to 1.04, p =
      .028) and WC (77.1 to 75.0 cm, p < .0001) in the HB group (N = 118) compared with
      an increase in zBMI (1.14 to 1.23, p = .046) and a minimal WC change in the
      control group (N = 61). Prevalence of elevated BP did not change in the HB group,
      but increased from 16.7% to 31.7% in the control group (p = .026). General linear
      model analysis revealed a significant interaction between time, group, and zBMI
      (p = .001), weight status (p = .014), nutritious beverage knowledge (p = .018),
      and healthy living and self-esteem score (p = .005). CONCLUSIONS: The HB program
      is a promising school-based strategy for addressing obesity and self-esteem in
      Aboriginal children.

PMID- 23879780
TI  - Associations between perceptions of school connectedness and adolescent health
      risk behaviors in South African high school learners.
AB  - BACKGROUND: This study investigated the relationship between school connectedness
      and health risk behaviors, specifically, substance abuse, violence-related
      behaviors, sexual risk behaviors, and suicidal ideation among school-going
      adolescents. School connectedness was understood to encompass a range of aspects
      pertaining to a learner's sense of belonging to the school. We hypothesized that
      strong perceptions of school connectedness will more likely be associated with
      lower levels of risk behaviors among school-going adolescents. METHODS: The study
      was conducted in 2 neighboring public co-educational schools in Durban, South
      Africa. Independent measures assessed school connectedness, substance abuse,
      violence-related behaviors, sexual risk behaviors, and suicidal ideation.
      RESULTS: Strong negative correlations were found between adolescents' perceptions
      of school connectedness and the 4 health risk behaviors, particularly suicidal
      ideation. The relative importance of risk factors was also evidenced in the
      sample. CONCLUSIONS: Adolescents with lower perceptions of school connectedness
      were more likely to engage in various risk behaviors, supporting the literature
      that a lack of school connectedness can act as a risk factor for adolescent
      involvement in clustering of risk behaviors. Further the relative weighting of
      individual risk factors, it is argued, was an effect of the sociocultural context
      of the study.

PMID- 23879781
TI  - Patterns of physical activity outside of school time among Japanese junior high
      school students.
AB  - BACKGROUND: Physical activity is beneficial for adolescent health. The physical
      activity patterns of Japanese adolescents are relatively unknown. Therefore, this
      study aimed to describe the current patterns of physical activity and to identify
      sex and grade differences among them. METHODS: The participants comprised 714
      Japanese adolescents aged 12 to 15 years old (boys N = 372, girls N = 342) from a
      public junior high school in Okayama, Japan. Physical activity at school, outside
      of school after hours, and during lunch recess as well as the total leisure time
      in a usual week was assessed with a 5-item questionnaire. To assess the
      differences in the physical activity patterns by sex and grade, independent t
      tests and analysis of variance (ANOVA) were conducted, respectively. RESULTS:
      Boys spent significantly more time in physical activity both inside and outside
      of school settings than girls (p < .05). Higher grade students were significantly
      less active than lower grade students (p < .05). Furthermore, the physical
      activity patterns across the grades differed between settings (at school, outside
      of school during the after-school period, lunchtime recess, and at home).
      CONCLUSION: To increase physical activity levels among Japanese adolescents,
      implementation of after-school programs or environmental modifications developed
      within the school setting could be effective strategies.

PMID- 23879782
TI  - Fitness change and subsequent academic performance in adolescents.
AB  - BACKGROUND: This study examined the association between fitness change and
      subsequent academic performance in Taiwanese schoolchildren from 7th grade to 9th
      grade. METHODS: The 7th graders from 1 junior high school district participated
      in this study (N = 669). Academic performance was extracted from school records
      at the end of each grade. Cardiovascular (CV) fitness, sit-and-reach flexibility,
      bent-leg curl-ups, and height and weight for calculating body mass index (BMI)
      were assessed at the start of each grade. RESULTS: The results showed that
      improvement in CV fitness, but not muscular endurance or flexibility, is
      significantly related to greater academic performance. A weak and nonsignificant
      academic-BMI relationship was seen. CONCLUSION: CV fitness exhibits stronger
      longitudinal associations with academic performance than other forms of fitness
      or BMI for adolescents.

PMID- 23879783
TI  - Effects of a 2-year school-based intervention of enhanced physical education in
      the primary school.
AB  - BACKGROUND: This study aimed to assess whether a school-based physical education
      intervention was effective in improving physical abilities and influencing daily
      physical activity habits in primary school children. The possible effect on body
      mass index (BMI) was also considered. METHODS: Twenty-six 3rd-grade classes were
      randomly selected stratifying by geographic location (city, plain, hills) and
      were assigned either to an intervention (127 boys; 120 girls) or to a traditional
      (129 boys; 121 girls) physical education program. At baseline (age: 8-9 years)
      and after a 2-year follow-up (age: 10-11 years), information was collected about
      sport participation and daily activity habits using a self-administered
      questionnaire. Height, weight, and BMI were measured and physical performance was
      assessed by means of standardized tests. RESULTS: The enhanced program of
      physical education was effective in improving physical abilities of children and
      determining a decrease (boys: 10%; girls: 12%) in daily sedentary activities
      (preintervention versus postintervention, p < .05; intervention versus control
      group, p < .01). The percentages of overweight and obese children did not vary
      significantly, but the experimental group showed a significantly lower rise in
      BMI compared to the control group (p < .001). CONCLUSION: The school proved to be
      an ideal setting for promoting physical activity and achieving the required daily
      activity levels.

PMID- 23879784
TI  - Information and communication technology: students' health education in 1st- to
      6th-grade South Korea elementary schools.
AB  - BACKGROUND: The purposes of this study were to (1) identify school nurses'
      awareness of information and communication technology (ICT) use in students'
      health education and (2) explore the barriers or reasons for the adoption of ICT
      in school nursing practice, while (3) presenting strategies to speed ICT
      diffusion and dissemination into practice. METHODS: For data collection, 209
      primary school nurses in K province of Korea were selected and e-mailed the
      questionnaires. Collected data were analyzed as frequency, percentages, and chi
      square tests. RESULTS: The major reasons to adopt ICT were increasing school
      nurses' confidence in providing health education and improving teaching methods
      using diverse multimedia. The major barriers to utilization of ICT were lack of
      time for preparation of educational materials, lack of software availability, and
      lack of computer skills of school nurses and students. Several strategies were
      suggested to speed the diffusion of ICT into students' health education, such as
      integrating a health education course into regular curriculum. CONCLUSIONS: It is
      important to identify barriers and reasons for adoption of ICT in school nursing.
      In addition, strategies should be emphasized that result in more rapid diffusion
      of these technologies in school nursing practice.

PMID- 23879785
TI  - Influencing factors of sedentary behavior in European preschool settings: an
      exploration through focus groups with teachers.
AB  - BACKGROUND: Sedentary behavior refers to activities involving sitting down and
      reclining (eg, watching TV, using the computer) and has been associated with
      different health outcomes. In preschool, children are sedentary for 50% to 80% of
      the time, in the classroom as well as during recess. Because of the absence of
      qualitative studies examining influencing factors of preschoolers' sedentary
      behavior in preschool settings, this study explored teachers' opinions on
      potentially influencing factors of this behavior. METHODS: Eighty-seven teachers
      of 4- to 6-year-old preschoolers from 6 European countries participated in a
      total of 18 focus groups between October 2010 and January 2011. Key findings were
      reported separately by country, and were independently analyzed by 2 researchers
      using qualitative content analysis. RESULTS: Teachers perceive the lack of play
      space and small classroom size as being influential factors on preschoolers'
      sedentary behavior; increasing play equipment and using teachers' prompts are
      mentioned as ways to stimulate children to be less sedentary on the playground.
      Computer use is reported to be more common in preschool than watching TV.
      CONCLUSION: Interventions should focus on increasing teachers' awareness of how
      sedentary preschoolers are during the preschool day. Teachers also should be
      informed about strategies to decrease sedentariness in the classroom and on the
      playground.

PMID- 23879786
TI  - Data collection procedures for school-based surveys among adolescents: the Youth
      in Europe Study.
AB  - BACKGROUND: Collection of valid and reliable surveillance data as a basis for
      school health promotion and education policy and practice for children and
      adolescence is of great importance. However, numerous methodological and
      practical problems arise in the planning and collection of such survey data that
      need to be resolved in order to ensure the validity of the data and to maximize
      the response rate without being prohibitively costly. METHOD: This article builds
      on a 15-yearlong experience of such annual data collections in Iceland and
      describes the preparation, process, and collection of data that provide a common
      methodologic framework for the school-based survey, Youth in Europe, a population
      based survey of 14- to 16-year-old adolescents, being collected across 18
      European cities now participating in the European Cities Against Drugs (ECAD)
      program. RESULTS: We identified 11 critical steps for developing and implementing
      the surveys in light of the recent literature on the preparation and
      implementation practices in school-based data collection among adolescents.
      CONCLUSION: Limiting the disruption of daily operations in schools while at the
      same time ensuring both quality and clarity of data collection procedures in
      school-based surveys are of paramount importance for researchers, school
      personnel, and students.

PMID- 23879787
TI  - School-based programs aimed at the prevention and treatment of obesity: evidence
      based interventions for youth in Latin America.
AB  - BACKGROUND: Rapidly rising childhood obesity rates constitute a public health
      priority in Latin America which makes it imperative to develop evidence-based
      strategies. Schools are a promising setting but to date it is unclear how many
      school-based obesity interventions have been documented in Latin America and what
      level of evidence can be gathered from such interventions. METHODS: We performed
      a systematic review of papers published between 1965 and December 2010.
      Interventions were considered eligible if they had a school-based component, were
      done in Latin America, evaluated an obesity related outcome (body mass index
      [BMI], weight, %body fat, waist circumference, BMI z-score), and compared youth
      exposed vs not exposed. RESULTS: Ten studies were identified as having a school
      based component. Most interventions had a sample of normal and overweight
      children. The most successful interventions focused on prevention rather than
      treatment, had longer follow-ups, a multidisciplinary team, and fewer limitations
      in execution. Three prevention and 2 treatment interventions found sufficient
      improvements in obesity-related outcomes. CONCLUSIONS: We found sufficient
      evidence to recommend school-based interventions to prevent obesity among youth
      in Latin America. Evidence-based interventions in the school setting should be
      promoted as an important component for integrated programs, policies, and
      monitoring frameworks designed to reverse the childhood obesity in the region.

PMID- 23879789
TI  - Pharmacokinetic profile of a new diclofenac prodrug without gastroulcerogenic
      effect.
AB  - Gastrotoxicity is a major problem for long-term therapy with non-steroidal anti
      inflammatory drugs (NSAIDs). DICCIC (1-(2,6-dichlorophenyl)indolin-2-one) is a
      new diclofenac prodrug, which has proven anti-inflammatory activity without
      gastroulcerogenic effect. The aim of this work was to compare the pharmacokinetic
      profiles of diclofenac from DICCIC (7.6 mg/kg equivalent to 8.1 mg/kg diclofenac)
      and diclofenac (8.1 mg/kg) administration in Wistar rats weighing 250-300 g
      (n=20). The doses were calculated by interspecific allometric scaling based on
      the 2 mg/kg from diary human dose of diclofenac. Blood samples were collected in
      heparinized tubes via the femoral artery through the implanted catheter. The
      plasma was separated and quantitation was made in a HPLC system with a UV-Vis
      detector. The confidence limits of the bioanalytical method were appropriate for
      its application in a preclinical pharmacokinetic study. The AUC of diclofenac
      from DICCIC (53.7+/- 5.8 ug/mL.min) was significantly less (Mann Whitney test,
      p<0.05) than that of diclofenac from diclofenac administration (885.9 +/- 124,8
      ug/mL.min). Terminal half-life of diclofenac from DICCIC (50.1 +/- 17.2 min) was
      significantly less (Mann Whitney test, p<0.05) than that of diclofenac from
      diclofenac administration (247.4 +/- 100.9 min). Still the parameters clearance
      and distribution volume were calculated for diclofenac from diclofenac, whose
      results were 9.2 +/-1.2 mL/min.kg and 3.3 +/-1.2 L/kg, respectively. The results
      of DICCIC from DICCIC administration were 108.9 +/- 19.6 mL/min.kg and 7.8 +/-
      2.4 L/kg for clearance and distribution volume, respectively. The pharmacokinetic
      profile demonstrated that there was an increase in diclofenac elimination and a
      lower exposure to diclofenac with administration of DICCIC compared to
      diclofenac. 

PMID- 23879788
TI  - Laparoscopic resection of hepatocellular carcinoma: a French survey in 351
      patients.
AB  - OBJECTIVES: Current clinical studies report the results of laparoscopic resection
      of hepatocellular carcinoma (HCC) obtained in small cohorts of patients. Because
      France was involved in the very early development of laparoscopic surgery, the
      present study was conducted in order to report the results of a large,
      multicentre experience. METHODS: A total of 351 patients underwent laparoscopic
      liver resection for HCC during the period from 1998 to 2010 in nine French
      tertiary centres. Patient characteristics, postoperative mortality and morbidity,
      and longterm survival were retrospectively reviewed. RESULTS: Overall, 85% of the
      study patients had underlying liver disease. Types of resection included wedge
      resection (41%), left lateral sectionectomy (27%), segmentectomy (24%), and major
      hepatectomy (11%). Median operative time was 180 min. Conversion to laparotomy
      occurred in 13% of surgeries and intraoperative blood transfusion was necessary
      in 5% of patients. The overall morbidity rate was 22%. The 30-day postoperative
      mortality rate was 2%. Negative resection (R0) margins were achieved in 92% of
      patients. Rates of overall and progression-free survival at 1, 3 and 5 years were
      90.3%, 70.1% and 65.9%, and 85.2%, 55.9% and 40.4%, respectively. CONCLUSIONS:
      This multicentre, large-cohort study confirms that laparoscopic liver resection
      for HCC is a safe and efficient approach to treatment and can be proposed as a
      first-line treatment in patients with resectable HCC.

PMID- 23879790
TI  - A transcellular assay to assess the P-gp inhibition in early stage of drug
      development.
AB  - To provide a fast assessment in predicting P-gp-mediated DDI risk during early
      stage of drug development, a transcellular P-gp inhibition assay using two
      concentrations is presented in the present study. The efflux ratios of loperamide
      in the presence of forty-five commercial compounds at two concentrations were
      measured and compared to that of six concentrations in human P-gp cDNA-expressing
      LLC-PK1 cells (LLC-MDR1). The inhibition potency calculated from the change on
      the efflux ratio (ER) and on the net secretory flux (NSF) of loperamide was
      investigated. The P-gp inhibition potency was defined as potent (IC50 < 1 uM),
      moderate (1 uM < IC50 < 10 uM), or weak (IC50 > 10 uM). The results using 1 uM
      and 10 uM of inhibitor concentrations provided the best correlation and are most
      consistent with those generated from a 6-point approach. 

PMID- 23879791
TI  - Local conformation and intermolecular interaction of rigid ring polymers are not
      always the same as the linear analogue: cyclic amylose tris(phenylcarbamate) in
      Theta solvents.
AB  - Small-angle X-ray scattering and static and dynamic light scattering measurements
      were made for cyclic amylose tris(phenylcarbamate) (cATPC) of which weight
      average molar mass M(w) ranges from 1.3 * 10(4) to 1.5 * 10(5) to determine their
      z-average mean square radius of gyration <S(2)>z, particle scattering function
      P(q), hydrodynamic radius R(H), and second virial coefficient A2 in methyl
      acetate (MEA), ethyl acetate (EA), and 4-methyl-2-pentanone (MIBK). The obtained
      <S(2)>z, P(q), and R(H) data were analyzed in terms of the wormlike ring to
      estimate the helix pitch per residue h and the Kuhn segment length lambda(-1)
      (the stiffness parameter, twice the persistence length). Both h and lambda(-1)
      for cATPC in MEA, EA, and MIBK are smaller than those for linear amylose
      tris(phenylcarbamate) (ATPC) in the corresponding solvent and the discrepancy
      becomes more significant with increasing the molar volume of the solvent. This
      indicates that not every rigid ring has the same local helical structure and
      chain stiffness as that for the linear polymer in the M(w) range investigated
      while infinitely long ring chains should have the same local conformation. This
      conformational difference also affects A2. In actuality, negative A2 was observed
      for cATPC in MIBK at the Theta temperature of linear ATPC whereas intermolecular
      topological interaction of ring polymers increases A2.

PMID- 23879792
TI  - Development and partial validation of a mouse model for predicting drug
      hypersensitivity reactions.
AB  - Animal models that can be used to predict the allergenic potential of drug
      candidates have not been adequately optimized, validated, or characterized. While
      initial validation data from an inter-laboratory study of the mouse lymph node
      proliferation assay (LNPA) appeared promising, no additional investigations in
      this model have been reported. The objectives of this study were to use positive
      and negative control drugs to further optimize and validate the LNPA utilizing a
      non-radioactive endpoint and determine the sensitivity, specificity, and
      predictivity of the model. Drugs associated with hypersensitivity reactions in
      the literature were chosen to test in the model in addition to drugs with few or
      no reports of hypersensitivity. Mice received a subcutaneous injection of drug or
      vehicle into the scruff of the neck once daily for a period of 3 days. On Day 6,
      draining lymph nodes were harvested, single cell suspensions prepared, and total
      cell numbers determined for each animal by flow cytometry. A stimulation index
      was calculated by dividing the mean total cell number for the drug-treated group
      by the mean total cell number for the vehicle-treated animals. Based on
      statistical analysis of the data, animals with a total cell number >=2.5* the
      mean of the vehicle group were classified as 'responders'. Based on data
      generated to date with 12 positive control and six negative control drugs, the
      model had a sensitivity of 75%, a specificity of 74%, and a relatively good
      predictive value (measured by the Receiver Operating Characteristic AUC of 0.80).
      The data here suggest that this model may be a useful tool for identifying drug
      candidates with the potential to produce allergic responses in the clinic. Future
      studies will investigate the mechanism(s) for the lymph node responses in order
      to develop additional endpoints that may increase the sensitivity and specificity
      of the model.

PMID- 23879793
TI  - Immunomodulating effects and hypersensitivity reactions caused by Northeast
      Indian black fly salivary gland extract.
AB  - The genus Simulium, black fly (Diptera), comprises >1800 species worldwide, of
      which 67 species under six subgenera have been well studied in India. While at
      the extreme, black fly bites can cause onchocerciasis or river blindness, the
      majority of clinical observations indicate mainly severe pain and continuous
      itching at bite sites. This investigation experimentally observed that black fly
      salivary extract (BFSE) causes unique biologic effects including
      immunomodulation, anti-coagulation, and hypersensitivity reactions in Wistar
      rats. Salivary glands from black flies were isolated, extracted in saline, and
      then ~800 ng extract (BFSE) subcutaneously injected into rats. To evaluate
      potential immunosuppressive activity of the BFSE, serum levels of interleukins
      [IL]-6 and -10 and tumor necrosis factor [TNF]-alpha were assayed. To assess the
      BFSE impact on coagulation, activated partial thromboplastin time (aPTT),
      prothrombin time (PT), and bleeding time, as well as generation of coagulation
      activated factors I, IX, and X were analyzed. Anaphylaxis induction was monitored
      via electrocardiogram (ECG) and measures of blood pressure and rectal
      temperature. The data showed that BFSE treatment resulted in a significantly
      prolonged aPTT, PT, and bleeding time and reversibly inhibited generation of
      coagulation activated factors I, IX, and X. The extract also led to a prolonged
      (up to 48 h) suppression of serum IL-6, IL-10, and TNFalpha production. While
      these results suggest that BFSE possesses anti-thrombotic, anti-coagulant, and
      immunomodulatory activities, importantly, they also indicate that the extract has
      a capacity to induce anaphylaxis and acute cardiotoxicity.

PMID- 23879795
TI  - Hematological disease a further association with small bowel angioectasia?

PMID- 23879794
TI  - Expression of cyclo-oxygenases-1 and -2, and microsomal prostaglandin E synthase
      1 in penile and preputial papillomas and squamous cell carcinomas in the horse.
AB  - REASONS FOR PERFORMING STUDY: Penile and preputial papilloma and squamous cell
      carcinoma (SCC) are commonly diagnosed in horses. Papillomas have the potential
      to progress to potentially lethal SCC. Knowledge of pathogenetic mechanisms may
      help in prevention and definition of treatment targets. STUDY DESIGN:
      Retrospective study using archived material. OBJECTIVES: To determine the
      expression of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2) and microsomal
      prostaglandin E synthase-1 (mPGES-1) in penile and preputial normal tissue,
      papilloma and SCC in horses, and whether expression of these enzymes is
      influenced by degree of inflammation and differentiation grade. METHODS: Tumour
      differentiation grade, degree of inflammation and COX-1, COX-2 and mPGES-1
      expression in 75 formalin-fixed paraffin embedded samples of penile and preputial
      papilloma and SCC of 68 horses were investigated by histopathology and
      immunohistochemistry. RESULTS: Inflammation was more prominent in SCC compared
      with papilloma. No correlation between expression of COX-1 or COX-2 and
      inflammation was found. Expression of mPGES-1 was weakly correlated with
      inflammation. Expression of COX-1, COX-2 and mPGES-1 was found in 42.6%, 50.7%
      and 96.0% of lesions respectively, but less than 1% of cells were immunopositive
      for COX-1 and COX-2 in 59.4% and 84.2% of cases respectively. Expression of COX-1
      was moderately negatively correlated with differentiation grade, COX-2 was not
      correlated and mPGES-1 was poorly negatively correlated. CONCLUSIONS: Expression
      of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX
      inhibitors may thus be of little value for prevention or treatment. Microsomal
      PGES-1 is more prominently expressed in well-differentiated tissue compared with
      poorly differentiated tissue. Further research on the role of mPGES-1 in
      carcinogenesis is needed to assess its potential use as a treatment target.
      Knowledge of arachidonic pathway enzyme expression and their role in equine
      penile and preputial carcinogenesis may help in developing preventive and
      therapeutic strategies.

PMID- 23879796
TI  - Rapid and scalable human stem cell differentiation: now in 3D.

PMID- 23879798
TI  - Acceleration patterns in the lower and upper trunk during running.
AB  - The purpose of the present study was to relate 3D acceleration patterns of the
      lower and upper trunk during running to running gait cycle, assess the validity
      of stride duration estimated from acceleration patterns, investigate speed
      dependent changes in acceleration, and examine the test-retest reliability of
      these parameters. Thirteen healthy young men performed two running trials each on
      a treadmill and on land at three speeds (slow, preferred, and fast). The 3D
      accelerations were measured at the L3 spinous process (lower trunk) and the
      ensiform process (upper trunk) and synchronised with digital video data. The
      amplitude and root mean square of acceleration and stride duration were
      calculated and then analysed by three-way analysis of variance to test effects of
      running conditions, device location, and running speed. Bland-Altman analysis was
      used to evaluate the test-retest reliability. Marked changes in acceleration were
      observed in relation to foot strike during running. Stride durations calculated
      from the vertical accelerations were nearly equal to those estimated from video
      data. There were significant speed effects on all parameters, and the low test
      retest reliability was confirmed in the anterior-posterior acceleration during
      treadmill running and the anterior-posterior acceleration at slow speed during
      treadmill and overground running.

PMID- 23879797
TI  - Sub-inhibitory concentrations of some antibiotics can drive diversification of
      Pseudomonas aeruginosa populations in artificial sputum medium.
AB  - BACKGROUND: Pseudomonas aeruginosa populations within the cystic fibrosis lung
      exhibit extensive phenotypic and genetic diversification. The resultant
      population diversity is thought to be crucial to the persistence of infection and
      may underpin the progression of disease. However, because cystic fibrosis lungs
      represent ecologically complex and hostile environments, the selective forces
      driving this diversification in vivo remain unclear. We took an experimental
      evolution approach to test the hypothesis that sub-inhibitory antibiotics can
      drive diversification of P. aeruginosa populations. Replicate populations of P.
      aeruginosa LESB58 were cultured for seven days in artificial sputum medium with
      and without sub-inhibitory concentrations of various clinically relevant
      antibiotics. We then characterised diversification with respect to 13 phenotypic
      and genotypic characteristics. RESULTS: We observed that higher population
      diversity evolved in the presence of azithromycin, ceftazidime or colistin
      relative to antibiotic-free controls. Divergence occurred due to alterations in
      antimicrobial susceptibility profiles following exposure to azithromycin,
      ceftazidime and colistin. Alterations in colony morphology and pyocyanin
      production were observed following exposure to ceftazidime and colistin only.
      Diversification was not observed in the presence of meropenem. CONCLUSIONS: Our
      study indicates that certain antibiotics can promote population diversification
      when present in sub-inhibitory concentrations. Hence, the choice of antibiotic
      may have previously unforeseen implications for the development of P. aeruginosa
      infections in the lungs of cystic fibrosis patients.

PMID- 23879799
TI  - Objectively-measured physical activity and body weight in Japanese pre-schoolers.
AB  - BACKGROUND: The prevalence of thinness has increased among Japanese children.
      AIM: The purpose of this study was to examine the association between physical
      activity and body mass index (BMI) among Japanese pre-school children. SUBJECTS
      AND METHODS: Subjects were 425 4-6-year-old Japanese girls and boys. Their
      weights were classified as normal, overweight or thin, based on Cole's
      international cut-offs for BMI. Physical activity was assessed using a triaxial
      accelerometer (ActivTracer, GMS) for 6 consecutive days. RESULTS: Physical
      activity in overweight children was comparable to that in normal-weight children
      after controlling for age and gender. However, thin children spent significantly
      greater time engaged in low-intensity activities (physical activity ratio < 2)
      and spent less time engaged in light-intensity physical activity (2 <= physical
      activity ratio < 3) and moderate-to-vigorous physical activity (physical activity
      ratio  >= 3) than normal-weight and overweight children, and less time engaged in
      higher-intensity physical activity (physical activity ratio >= 4) than normal
      weight children. Moreover, thin children spent significantly less time engaged in
      locomotive physical activity than normal-weight or overweight children.
      CONCLUSION: This study suggests that thinness, rather than excess weight, is
      associated with decreased light, moderate and high intensity physical activity in
      Japanese pre-school children.

PMID- 23879800
TI  - Psychometric properties of the Cognitive Failures Questionnaire.
AB  - The Cognitive Failures Questionnaire (CFQ) is used in ergonomics research to
      measure behavioural problems associated with attentiveness and memory in everyday
      life. CFQ scores have been related to constructs such as accident proneness and
      outcomes such as human error and psychological strain. The two-year test-retest
      reliability of the CFQ is reported together with the findings of factor analyses
      of CFQ data from 535 respondents. Evidence for the predictive and criterion
      validity and internal reliability of the CFQ is provided. Psychological strain
      was measured concurrently with CFQ on both testing occasions, two years apart.
      The test-retest reliability of the summated CFQ score was found to be 0.71, while
      for the General Health Questionnaire (GHQ-12) strain measure it was 0.32.The
      relative variance stability was five times greater for the CFQ than the GHQ,
      indicating that scores on these questionnaires are not covariates. The use of the
      CFQ as a measure of cognitive control capacity is also discussed. PRACTITIONER
      SUMMARY: Ergonomists have long been interested in human error and the role of
      high work demands due to poor equipment design and excessive workload. The CFQ
      measures attentiveness in daily life and is shown to have excellent psychometric
      properties that make it suitable for use in both laboratory and field studies as
      a trait measure of attentiveness in daily life.

PMID- 23879801
TI  - Estimated impact of aggressive empirical antiviral treatment in containing an
      outbreak of pandemic influenza H1N1 in an isolated First Nations community.
AB  - BACKGROUND: The 2009 influenza A (H1N1) pandemic was mild by historical
      standards, but was more severe in isolated Canadian Indigenous communities.
      Oseltamivir was used aggressively for outbreak control in an isolated northern
      Ontario First Nations community. We used mathematical modeling to quantify the
      impact of antiviral therapy on the course of this outbreak. METHODS: We used both
      a Richards growth model and a compartmental model to evaluate the characteristics
      of the outbreak based on both respiratory visits and influenza-like illness
      counts. Estimates of best-fit model parameters, including basic reproductive
      number (R0 ) and antiviral efficacy, and simulations, were used to estimate the
      impact of antiviral drugs compared to social distancing interventions alone.
      RESULTS: Using both approaches, we found that a rapidly growing outbreak slowed
      markedly with aggressive antiviral therapy. Richards model turning points
      occurred within 24 hours of antiviral implementation. Compartmental models
      estimated antiviral efficacy at 70-95%. Plausible estimates of R from both
      modeling approaches ranged from 4.0 to 15.8, higher than published estimates for
      southern Canada; utilization of aggressive antiviral therapy in this community
      prevented 962-1757 cases of symptomatic influenza and as many as 114 medical
      evacuations in this community. CONCLUSION: Although not advocated in other
      settings in Canada, aggressive antiviral therapy markedly reduced the impact of a
      pandemic-related influenza A (H1N1) outbreak in an isolated Canadian First
      Nations community in northern Ontario, Canada. The differential risk experienced
      by such communities makes tailored interventions that consider risk and lack of
      access to medical services, appropriate.

PMID- 23879802
TI  - Simulations of biased agonists in the beta(2) adrenergic receptor with
      accelerated molecular dynamics.
AB  - The biased agonism of the G protein-coupled receptors (GPCRs), where in addition
      to a traditional G protein-signaling pathway a GPCR promotes intracellular
      signals though beta-arrestin, is a novel paradigm in pharmacology. Biochemical
      and biophysical studies have suggested that a GPCR forms a distinct ensemble of
      conformations signaling through the G protein and beta-arrestin. Here we report
      on the dynamics of the beta2 adrenergic receptor bound to the beta-arrestin and G
      protein-biased agonists and the empty receptor to further characterize the
      receptor conformational changes caused by biased agonists. We use conventional
      and accelerated molecular dynamics (aMD) simulations to explore the
      conformational transitions of the GPCR from the active state to the inactive
      state. We found that aMD simulations enable monitoring of the transition within
      the nanosecond time scale while capturing the known microscopic characteristics
      of the inactive states, such as the ionic lock, the inward position of F6.44, and
      water clusters. Distinct conformational states are shown to be stabilized by each
      biased agonist. In particular, in simulations of the receptor with the beta
      arrestin-biased agonist N-cyclopentylbutanepherine, we observe a different
      pattern of motions in helix 7 when compared to simulations with the G protein
      biased agonist salbutamol that involves perturbations of the network of
      interactions within the NPxxY motif. Understanding the network of interactions
      induced by biased ligands and the subsequent receptor conformational shifts will
      lead to development of more efficient drugs. 

PMID- 23879803
TI  - Accelerated corneal collagen cross-linking for progressive keratoconus.
AB  - PURPOSE: To evaluate the efficacy of accelerated corneal cross-linking (CXL)
      procedure for progressive keratoconus. MATERIALS AND METHODS: Twenty-three eyes
      of 23 patients undergone accelerated CXL procedure were evaluated preoperatively
      and postoperatively at 1st, 3rd and 6th month for uncorrected distant visual
      acuity (UDVA), best corrected distant visual acuity (CDVA), spherical error,
      cylindrical error, spherical equivalent (SE), keratometric values and thinnest
      corneal thickness (TCT) values with corneal topography by Scheimpflug camera and
      endothelial cell density (ECD). RESULTS: The mean UDVA was improved from 0.97 +/-
      0.41 logarithm of minimal angle of resolution (logMAR) to 0.76 +/- 0.45 logMAR at
      the 6th month after CXL (p = 0.332). The mean CDVA was improved from 0.49 +/-
      0.30 logMAR to 0.34 +/- 0.22 logMAR at the 6th month after CXL (p = 0.026). The
      mean sphere was decreased from -4.47 +/- 4.1 diopter (D) to -3.79 +/- 3.86 D and
      the mean cylinder was decreased from -5.60 +/- 2.2 D to -4.55 +/- 1.98 D and the
      mean SE was decreased from -7.22 +/- 4.48 D to -6.36 +/- 4.34 D at the 6th month
      after CXL (p = 0.128, p = 0.002 and p = 0.045, respectively). Flat keratometry,
      steep keratometry, mean keratometry and maximum keratometry were significantly
      reduced at the 6th month after CXL (p = 0.025, p < 0.001, p = 0.004 and p = 0.03,
      respectively). TCT and ECD were not changed significantly the 6th month after CXL
      (p = 0.135 and p = 0.082, respectively). CONCLUSION: Accelerated CXL procedure
      was effective to stabilize progression of keratoconus with significant reduction
      in topographic keratometric values and significant increase in CDVA in 6 months.

PMID- 23879804
TI  - Investigating the utilization of radiological services by physician patients: a
      population-based cohort study in Taiwan.
AB  - BACKGROUND: Advances in radiology technology have contributed to a substantial
      increase in utilization of radiology services. Physicians, who are well educated
      in medical matters, would be expected to be knowledgeable about prudent or
      injudicious use of radiological services. The aim of this study was to evaluate
      differences in the utilization of radiology modalities among physician and non
      physician patients. METHODS: This nationwide population-based cohort study was
      carried out using data obtained from the Taiwan National Insurance Database from
      1997 to 2008. Physicians and comparison controls selected by propensity score
      matching were enrolled in the current study. The claims data of ambulatory care
      and inpatient discharge records were used to measure the utilization of various
      radiology modalities. Utilization rates of each modality were compared between
      physicians and non-physicians, and odds ratios of the utilization of each
      radiology modality were measured. Multiple logistic regression analysis was used
      to examine the predictors of X-ray, MRI, and interventional procedures
      utilization during the study period. RESULTS: The utilization of most radiologic
      services increased among physicians and the comparison group during the
      observation period. Compared to non-physicians, physicians had significantly
      higher utilization rates of computed tomography and magnetic resonance imaging
      (MRI) but lower utilization rates of X-rays, sonography, and interventional
      procedures. After adjusting for age, gender, major diseases, urbanicity, and
      residential regions, logistic regression analysis showed that, compared to non
      physicians, the physicians used significantly more MRI (odds ratio [OR]: 2.19,
      95% confidence interval [CI]: 1.68-2.84, P < 0.001) and significantly less X-rays
      and interventional procedures (OR: 0.85, 95% CI: 0.72-0.99, P = 0.04 for X-rays
      and OR: 0.67, 95% CI: 0.54-0.83, P < 0.001 for interventional procedures). Being
      a physician was a significant predictor of greater usage of MRI and of less usage
      of X-ray and interventional procedures. CONCLUSIONS: This study revealed
      different utilization patterns of X-rays, MRI, and interventional procedures
      between physician and non-physician patients, even after controlling for such
      factors as socioeconomic status and major diseases.

PMID- 23879805
TI  - Controlled fusion of synthetic lipid membrane vesicles.
AB  - Lipid membrane fusion is a fundamental noncovalent transformation as well as a
      central process in biology. The complex and highly controlled biological
      machinery of fusion has been the subject of intense investigation. In contrast,
      fewer synthetic approaches that demonstrate selective membrane fusion have been
      developed. Artificial recapitulation of membrane fusion is an informative pursuit
      in that fundamental biophysical concepts of biomembrane merger may be generally
      tested in a controlled reductionist system. A key concept that has emerged from
      extensive studies on lipid biophysics and biological membrane fusion is that
      selective membrane fusion derives from the coupling of surface recognition with
      local membrane disruption, or strain. These observations from native systems have
      guided the development of de novo-designed biomimetic membrane fusion systems
      that have unequivocally established the generality of these concepts in
      noncovalent chemistry. In this Account, we discuss the function and limitations
      of the artificial membrane fusion systems that have been constructed to date and
      the insights gained from their study by our group and others. Overall, the
      synthetic systems are highly reductionist and chemically selective, though there
      remain aspects of membrane fusion that are not sufficiently understood to permit
      designed function. In particular, membrane fusion with efficient retention of
      vesicular contents within the membrane-bound compartments remains a challenge. We
      discuss examples in which lipid mixing and some degree of vesicle-contents mixing
      is achieved, but the determinants of aqueous-compartment mixing remain unclear
      and therefore are difficult to generally implement. The ability to fully design
      membrane fusogenic function requires a deeper understanding of the biophysical
      underpinnings of membrane fusion, which has not yet been achieved. Thus, it is
      critical that biological and synthetic studies continue to further elucidate this
      biologically important process. Examination of lipid membrane fusion from a
      synthetic perspective can also reveal the governing noncovalent principles that
      drive chemically determined release and controlled mixing within nanometer-scale
      compartments. These are processes that figure prominently in numerous
      biotechnological and chemical applications. A rough guide to the construction of
      a functional membrane fusion system may already be assembled from the existing
      studies: surface-directed membrane apposition may generally be elaborated into
      selective fusion by coupling to a membrane-disruptive element, as observed over a
      range of systems that include small-molecule, DNA, or peptide fusogens. Membrane
      disruption may take different forms, and we briefly describe our investigation of
      the sequence determinants of fusion and lysis in membrane-active viral fusion
      peptide variants. These findings set the stage for further investigation of the
      critical elements that enable efficient, fully functional fusion of both membrane
      and aqueous compartments and the application of these principles to unite
      synthetic and biological membranes in a directed fashion. Controlled fusion of
      artificial and living membranes remains a chemical challenge that is biomimetic
      of native chemical transport and has a direct impact on drug delivery approaches.

PMID- 23879806
TI  - The effect of domestic laundry processes on fungal contamination of socks.
AB  - Tinea pedis is a common chronic skin disease. The role of contaminated clothes as
      a possible source of reinfection is not fully understood. This study was
      conducted to evaluate the efficacy of domestic laundering at different
      temperatures in the eradication of fungal pathogens from contaminated socks.
      Samples from 81 socks worn by patients suffering from tinea pedis underwent
      domestic laundering at either 40  degrees C or 60  degrees C. The socks were
      dried at room temperature; fungal cultures were taken from two samples from,
      respectively, the toe and heel areas of the socks. Samples from socks washed at
      40  degrees C revealed 29 (36%) positive fungal cultures, of which 14 came from
      the toe and 15 from the heel areas of socks. Trichophyton rubrum was isolated in
      four specimens, and Aspergillus spp. were found in 20 (70%) specimens. Samples
      from the same socks washed at 60  degrees C revealed five (6%) positive fungal
      cultures, of which three came from the toe and two from the heel areas of socks.
      Only Aspergillus spp. were detected. Yeasts were eradicated at 40  degrees C.
      Contravening current trends for energy saving and environmental protection,
      laundering at low temperatures is not effective in eradicating fungal pathogens,
      which requires high-temperature laundering at 60  degrees C.

PMID- 23879807
TI  - Interference with the germination and growth of Ulva zoospores by quorum-sensing
      molecules from Ulva-associated epiphytic bacteria.
AB  - Ulva zoospores preferentially settle on N-acylhomoserine lactone (AHL) producing
      marine bacterial biofilms. To investigate whether AHL signal molecules also
      affect the success and rate of zoospore germination in addition to zoospore
      attraction, the epiphytic bacteria associated with mature Ulva linza were
      characterized and bacterial isolates representative of this community tested for
      the ability to produce AHLs. Two of these AHL-producing isolates, Sulfitobacter
      spp. 376 and Shewanella spp. 79, were transformed with plasmids expressing the
      Bacillus spp. AHL lactonase gene aiiA to generate AHL-deficient variants. The
      germination and growth of U. linza zoospores was studied in the presence of these
      AHL-deficient strains and their AHL-producing counterparts. This revealed that
      the AHLs produced by Sulfitobacter spp. and Shewanella spp. or the bacterial
      products they regulate have a negative impact on both zoospore germination and
      the early growth of the Ulva germling. Further experiments with Escherichia coli
      biofilms expressing recombinant AHL synthases and synthetic AHLs provide data to
      demonstrate that zoospores germinated and grown in the absence of AHLs were
      significantly longer than those germinated in the presence of AHLs. These results
      reveal an additional role for AHLs per se in the interactive relationships
      between marine bacteria and Ulva zoospores. 

PMID- 23879808
TI  - Antiaging effects of astaxanthin-rich alga Haematococcus pluvialis on fruit flies
      under oxidative stress.
AB  - The microalga Haematococcus pluvialis (HP) is the best natural producer of
      astaxanthin (AX), which is a potent antioxidant with broad health benefits. The
      present study investigated the antiaging potential of HP biomass using the fruit
      fly Drosophila melanogaster as the animal model. The results showed that in wild
      type flies the treatment of HP induced the early mortality at a concentration of
      20 mg/mL, which was associated with the decreased enzymatic activities of CuZn
      superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) as well as the
      down-regulation of SOD1, SOD2, and catalase (CAT) at the transcriptional level.
      In SOD(n108) mutant flies, the supplementation of HP (10 or 20 mg/mL)
      significantly extended their lifespan and ameliorated the age-related decline in
      locomotor function. Further studies suggested that HP may play a role as a
      complement to the defective endogenous antioxidant system to exert such lifespan
      elongation effects. These results, taken together, strongly support the antiaging
      properties of HP and its therapeutic rather than preventive potential against
      aging-related diseases. 

PMID- 23879809
TI  - Statement of retraction.

PMID- 23879810
TI  - Potential mesenchymal stem cell therapy for skin diseases.
AB  - Mesenchymal stem cells (MSCs) are non-haematopoietic cells that reside in most
      tissues including adult bone marrow. MSCs have recently been extensively studied
      and used for clinical therapies, including skin wound healing. However, there are
      still many questions to be answered. In the viewpoint entitled 'Mesenchymal stem
      cell therapy in skin: why and what for?', Dr. Khosrotehrani provided a
      comprehensive overview for MSC properties and current progresses on clinical
      applications for various skin conditions. This viewpoint is therefore very
      helpful for both dermatologists and basic skin researchers to understand stem
      cells researches. 

PMID- 23879811
TI  - The birth of innate immunity.
AB  - Modern immunology has seen an apparent revolution with the recognition that human
      immune defense is not only the responsibility of bone marrow-derived leucocytes,
      but also dependent on a coordinated network of many cell types including
      epithelial cells, fibroblasts and neural elements. This classic paper by
      Alexander Fleming and V.D. Allison (British J of Exp Path, 111, 1922, 252) was
      largely forgotten for 75 years and describes the discovery that epithelia produce
      a protein with direct antimicrobial activity. Thus, this paper represents the
      birth of the field now referred to as innate immunity and first describes an
      antimicrobial protein (AMP). 

PMID- 23879813
TI  - Novel inhibitory effect of the antidiabetic drug voglibose on melanogenesis.
AB  - Overproduction of melanin can lead to medical disorders such as postinflammatory
      melanoderma and melasma. Therefore, developing antimelanogenic agents is
      important for both medical and cosmetic purposes. In this report, we demonstrated
      for the first time that the antidiabetic drug voglibose is a potent
      antimelanogenic agent. Voglibose is a representative antidiabetic drug possessing
      inhibitory activity towards human alpha-glucosidase; it blocked the proper N
      glycan modification of tyrosinase, resulting in a dramatic reduction of the
      tyrosinase protein level by altering its stability and subsequently decreasing
      melanin production. Acarbose, another antihyperglycaemic drug that has a lower
      inhibitory effect on human intracellular alpha-glucosidase compared with
      voglibose, did not cause any changes in either the N-glycan modification of
      tyrosinase or the tyrosinase protein level, indicating that voglibose was the
      most efficient antimelanogenic agent among the widely used antihyperglycaemic
      agents. Considering that voglibose was originally selected from the valiolamine
      derivatives in a screen for an oral antidiabetic drug with a strong inhibitory
      activity towards intestinal alpha-glucosidase and low cell permeability, we
      propose an alternative strategy for screening compounds from valiolamine
      derivatives that show high inhibitory activity towards human intracellular alpha
      glucosidases and high cell permeability, with the goal of obtaining
      antimelanogenic agents that are effective inside the cells. 

PMID- 23879812
TI  - Reduction of inflammatory slan (6-sulfo LacNAc) dendritic cells in psoriatic skin
      of patients treated with etanercept.
AB  - Dermal dendritic cells (DCs) play a central role in the immunopathology of
      psoriasis. We previously identified slanDCs as pro-inflammatory TNF-alpha, IL-23-
      and IL-12-producing DCs in human blood and as prominent inflammatory dermal TNF
      alpha secreting and CD11c-positive DC subset in psoriasis. Here, we ask for the
      effects of TNF-alpha-inhibition on inflammatory slanDCs in skin and blood of 10
      patients with psoriasis during 24 weeks of treatment with etanercept. Treatment
      with etanercept reduced the frequency of dermal slanDCs but did not induce
      apoptosis as determined by lack of increased active caspase-3-expression. In
      parallel, we found increased frequencies of slanDCs in blood which expressed
      lower levels of HLA-DR. Stimulating slanDCs isolated from the blood of healthy
      donors in vitro induced a strong production of IL-1beta, IL-6, IL-23 and IL
      12p70. This capacity was efficiently reduced in the presence of etanercept,
      thereby indicating that TNF-alpha is an autocrine stimulus for maturation and pro
      inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment
      with etanercept did reduce the number of dermal slanDCs in parallel to the
      overall expression of TNF-alpha and IL-23p19. However, successful treatment did
      not down-regulated the percentage of dermal slanDCs that stained positive for TNF
      alpha and IL-23p19 indicating that remaining slanDCs kept their pro-inflammatory
      capacity. This study provides novel insights into the immune regulatory
      properties of etanercept at the level of inflammatory slanDCs in vivo in skin and
      blood as well as in vitro. 

PMID- 23879814
TI  - Optical coherence tomography for presurgical margin assessment of non-melanoma
      skin cancer - a practical approach.
AB  - In the clinical setting, optical coherence tomography (OCT) is applicable for the
      non-invasive diagnosis of skin cancer and may in particular be used for margin
      definition prior to excision. In this regard, OCT may improve the success rate of
      removing tumor lesions more effectively, preventing repetitive excision, which
      may subsequently result in smaller excisions. In this study, we have aimed to
      evaluate the applicability of OCT for in vivo presurgical margin assessment of
      non-melanocytic skin tumors (NMSC) and to describe the feasibility of different
      scanning techniques. A total number of 18 patients planned for excision of
      lesions suspicious of NMSC were included in this study. Based on OCT, we defined
      the specific tumor margins on 19 lesions preoperatively using different scanning
      modalities. Sixty-one margin points and five complete tumor margins were analysed
      on 18 patients with a total of 19 lesions including 63% basal cell carcinoma
      (BCC) (n = 12), 16% (n = 3) squamous cell carcinoma (SCC) and 21% of other types
      of skin tumors (n = 4) were classified. In 84% of the cases (n = 16), the OCT
      defined lateral margins correctly indicated complete removal of the tumor. The
      surgical margins chosen by the surgeon never fell below the OCT-defined margin.
      Regarding the techniques of marginal definition, punctual tumor border scan in
      the perpendicular direction, with an extension of free-run scans for unsure cases
      can hardly be recommended. This study shows that suspected NMSC can effectively
      be confirmed, and furthermore, resection margin can be minimized under OCT
      control without reducing the rate of complete removal. 

PMID- 23879815
TI  - Genetic control of psoriasis is relatively distinct from that of metabolic
      syndrome and coronary artery disease.
AB  - Psoriasis is a common chronic inflammatory skin disease, associated with
      significant comorbidity, for example, metabolic syndrome (MetS) and coronary
      heart disease (CHD). This association implies that the risk to develop these
      diseases is commonly controlled or that the presence of one disease favours
      manifestation of the other. Therefore, we assessed the catalogue of genome-wide
      association studies (GWAS) to analyse whether psoriasis, MetS and CHD share
      susceptibility loci. Interestingly, genetic control of psoriasis is almost
      completely independent from both MetS and CHD. In contrast, MetS and CHD share 10
      common loci. Like by GWAS analysis, psoriasis susceptibility genes showed close
      clustering in Ingenuity Pathway Analysis, while genes conferring susceptibility
      to MetS and CHD were interlinked separately. These findings lead to the
      hypothesis that the clinically observed co-occurrence of psoriasis with MetS and
      CHD may be due to a common environmental factor, for example, diet, which is
      known as a risk factor for all of these diseases. 

PMID- 23879816
TI  - Characterization of skin-resident T cells using a crawl-out method and flow
      cytometry.
AB  - A large fraction of the skin-homing T-cell population resides in the skin even
      under resting, non-inflammatory conditions. Here, we used a crawl-out culture
      method to retrieve T cells from human skin and characterized them using flow
      cytometric analysis. On average, 48000 viable, non-proliferating cells were
      retrieved per biopsy. We found that human skin contains a larger fraction of IL
      17-, IL-4-, IL-10- and IL-22-positive T cells as compared with paired blood
      samples. Our research indicates that it is feasible to use the crawl-out method
      in combination with flow cytometry to characterize T-cell subpopulations in
      patient-derived skin biopsies. This method enables further study of the skin
      immune system and could function as a valuable tool for evaluation of the effects
      of immunotherapy in skin diseases. 

PMID- 23879817
TI  - Blue light irradiation suppresses dendritic cells activation in vitro.
AB  - Blue light is a UV-free irradiation suitable for treating chronic skin
      inflammation, for example, atopic dermatitis, psoriasis, and hand- and foot
      eczema. However, a better understanding of the mode of action is still missing.
      For this reason, we investigated whether dendritic cells (DC) are directly
      affected by blue light irradiation in vitro. Here, we report that irradiation
      neither induced apoptosis nor maturation of monocyte-derived and myeloid DC.
      However, subsequent DC maturation upon LPS/IFNgamma stimulation was impaired in a
      dose-dependent manner as assessed by maturation markers and cytokine release.
      Moreover, the potential of this DC to induce cytokine secretion from allogeneic
      CD4 T cells was reduced. In conclusion, unlike UV irradiation, blue light
      irradiation at high and low doses only resulted in impaired DC maturation upon
      activation and a reduced subsequent stimulatory capacity in allogeneic MLRs with
      strongest effects at higher doses. 

PMID- 23879818
TI  - Oral administration of poly-gamma-glutamic acid prevents the development of
      atopic dermatitis in NC/Nga mice.
AB  - Bacillus subtilis-derived poly-gamma-glutamic acid (gammaPGA) has demonstrated
      adjuvant activity in promoting Th1/Th17 cell differentiation. Here, the NC/Nga
      (NC) mouse model was used to determine whether gammaPGA modulates the outcome of
      atopic dermatitis (AD), which is known to be a Th2-biased immune disease. We
      found that oral administration of gammaPGA dramatically reduced the development
      of AD in NC mice. Antigen-presenting cells activated with gammaPGA produced pro
      inflammatory cytokines, such as IL12/23 and IFNgamma, which, in turn, induced the
      differentiation of Th1 and Th17 cells. Concomitantly, Th2 responses, such as high
      levels of serum IgE, were dramatically decreased. Furthermore, in vivo gammaPGA
      treatment altered several cellular components of allergic reactions, such as mast
      cells and eosinophils. Taken together, our results strongly demonstrate that in
      vivo treatment with gammaPGA at early time points can prevent the development of
      AD in NC mice and suggest that gammaPGA may have therapeutic applications for
      human AD. 

PMID- 23879820
TI  - Evaluation of elite table tennis players' technique effectiveness.
AB  - Abstract This study constructed a technique effectiveness evaluation formula for
      table tennis players based on the relationship between the scoring rate and usage
      rate of techniques and established evaluation criteria through the examination of
      224 matches of the world's top 35 players. It also built a competition
      performance formula with the score difference theory for the exploration of the
      correlation between player technique effectiveness and competition performance.
      The results showed the three indices - the technique effectiveness of the first
      and third strokes (TE1,3), the second and fourth strokes (TE2,4) and the after
      fourth strokes (TE>4) - could help better evaluate the technique effectiveness of
      elite players. The comparative analysis of Chinese elite table tennis players and
      players from other countries and regions revealed that Chinese players as a whole
      were 'excellent' in all the examined techniques except in the male's 'first and
      third strokes'; while players from other countries and regions were overall
      'general'. The case analysis of two of the world's top players further indicated
      that correlation analysis of technique effectiveness and competition performance
      could help identify the technique indices highly correlated with player
      competition performance.

PMID- 23879821
TI  - Predictors of excess cement and tissue response to fixed implant-supported
      dentures after cementation.
AB  - BACKGROUND: The cementation of fixed implant-supported restorations involves the
      risk of excess cement remaining in the peri-implant tissue that may cause a peri
      implant tissue response with attachment loss. PURPOSE: The aim was to study the
      peri-implant tissue response after cementation and to detect potential predictors
      of excess cement. MATERIAL AND METHODS: Clinical complications after cementation
      in several index cases led to a recall of all patients treated with a special
      methacrylate cement (one hundred five patients with one hundred eighty-eight
      implants) and systematic reevaluation of 71 patients (68%) with one hundred
      twenty-six implants (67%). In all cases, suprastructures including abutments were
      removed, and findings were documented. RESULTS: Implant diameter was
      significantly associated with the frequency of excess cement. Implant location or
      system had no significant effect. Excess cement in turn was associated with
      bleeding on probing, suppuration, and peri-implant attachment loss. In the
      absence of excess cement 58.8% of implants had no peri-implant attachment loss
      versus 37.3% when excess cement was present. With increasing retention time of
      the methacrylate cement, more peri-implant attachment loss was detected. However,
      the latter association was not significant. CONCLUSION: Larger diameters are
      significantly associated with excess cement in peri-implant tissue. Consequences
      of excess cement may be increased bleeding on probing, suppuration, and possibly
      peri-implant attachment loss.

PMID- 23879822
TI  - A surview of recent patents on anti-infective therapy for Clostridium difficile.
AB  - Clostridium difficile has become the most common infectious cause of healthcare
      associated diarrhea, with serious morbidity, prolonged hospitalization and even
      death. Treatment of the disease utilizing today's therapies does not guarantee a
      successful outcome. In the past decade, many new ideas and inventions have
      surfaced exploring different treatment strategies of Clostridium difficile
      associated diarrhea (CDAD). These treatments include antitoxins, novel
      antimicrobials, immunoglobulins and large inert synthetic compounds. In this
      paper, we survey of a number of representative patents issued from 2000 to the
      present targeting treatment of this difficult and dreaded disease. 

PMID- 23879823
TI  - Recent developments on coronavirus main protease/3C like protease inhibitors.
AB  - Coronaviruses have been thrust into the spotlight by the recurring novel human
      coronavirus infections following the 2003 SARS pandemic. In the years since the
      initial SARS outbreak, the arsenal to fight this virus family has been
      significantly increased by the rapid growth of coronavirus research. Among the
      potential viral drug targets, coronavirus 3C like proteases (3Cl) have emerged as
      the most popular drug target. A number of patented inhibitors with promising
      clinical potential have been developed via different methods of drug discovery,
      including virtual screening, natural product isolation and structure assisted
      rational drug design. This review serves as a summary of the progress in both the
      method of drug discovery and the related inhibitors against the coronavirus 3Cl
      protease. 

PMID- 23879824
TI  - Preserving hepatic artery flow during portal triad blood inflow occlusion reduces
      the outgrowth of hepatocarcinoma in mice after ischemia-reperfusion.
AB  - AIM: To investigate the effect of different hepatic vascular occlusion maneuvers
      on the growth of hepatocarcinoma after liver ischemia-reperfusion (I/R) injury.
      METHODS: A mice hepatocarcinoma model was established by portal vein injection of
      H22 hepatoma cells. After 3 days, the mice underwent sham operation, occlusion of
      portal triad (OPT), portal vein (OPV), or intermittent clamping (INT) operation.
      The hepatic I/R injury, pathological changes, hepatic replacement area,
      proliferative cell nuclear antigen expression, and extracellular signal-regulated
      kinase (ERK) 1/2 activation were assessed 5 days after reperfusion. RESULTS:
      Alanine aminotransferase and aspartate aminotransferase levels in the OPV group
      were significantly lower than those in the OPT and INT groups at 24 h after
      reperfusion. The hepatic injury of clamped liver lobes in the OPV group,
      represented by histopathological alterations and myeloperoxidase activity, was
      much slighter than that in the OPT and INT groups. The values of hepatic
      replacement area in the sham operation, OPT, OPV, and INT groups were 7.661
      2.55%, 35.61 1 4.23%, 9.02 1 3.01%, and 19.95 1 4.10%, respectively.
      Proliferative cell nuclear antigen expression and ERK1/2 activation of tumor
      cells were the highest in the OPT group, and the lowest in the OPV and INT
      groups. CONCLUSION: Preserving hepatic artery flow during portal triad blood
      inflow occlusion substantially inhibits the outgrowth of hepatocarcinoma via
      attenuating hepatic I/R injury in a murine liver tumor model. These results
      suggest a better prevention of hepatic tumor outgrowth after hepatectomy by using
      the selective portal vein clamping method in liver cancer patients.

PMID- 23879825
TI  - Hyperbaric oxygen therapy does not improve the effects of standardized treatment
      in a severe attack of ulcerative colitis: a prospective randomized study.
AB  - BACKGROUND AND AIMS: Complementary therapy options are needed in the treatment of
      active ulcerative colitis (UC). Hyperbaric oxygen therapy (HBOT) has been shown
      to have positive effects in experimental models of colitis and perianal Crohn's
      disease. METHODS: In the present prospective randomized open-label study, HBOT in
      addition to conventional medical treatment was compared with conventional
      treatment alone. The primary objective in this study was improved clinical
      outcome evaluated by Mayo score, laboratory tests and fecal weight. The secondary
      objectives were improvement in health-related quality of life, avoidance of
      colectomy and evaluation of HBOT safety. RESULTS: The authors found no
      statistically significant differences between the treatment groups in any of the
      assessed variables. CONCLUSION: The study results do not support the use of HBOT
      as a treatment option in a severe attack of UC.

PMID- 23879826
TI  - Exotic diseases - a growing concern?

PMID- 23879827
TI  - Treatment of canine idiopathic immune-mediated haemolytic anaemia with
      mycophenolate mofetil and glucocorticoids: 30 cases (2007 to 2011).
AB  - OBJECTIVE: To compare short-term outcome and frequency of adverse events for dogs
      with idiopathic immune-mediated haemolytic anaemia treated with glucocorticoids
      and mycophenolate mofetil vs alternate immunosuppressive protocols. METHODS: A
      retrospective study of medical case records of dogs with immune-mediated
      haemolytic anaemia was conducted. Data collected included signalment,
      clinicopathological data, medications administered, duration of hospitalization,
      short-term survival and adverse events. Variables were compared between dogs
      treated with glucocorticoids and mycophenolate mofetil (mycophenolate mofetil
      group) vs dogs treated with other two-drug immunosuppressive protocols (combined
      group). RESULTS: Sixty-four cases of idiopathic immune-mediated haemolytic
      anaemia were identified. Two dogs were euthanased without treatment, three
      received glucocorticoids alone, and seven received two additional drugs. Fifty
      two dogs received glucocorticoids and additional immunosuppressive medications:
      30 mycophenolate mofetil, 15 cyclosporine, 6 azathioprine and 1 human
      immunoglobulin. There was no significant difference between the discharge rate,
      30-day or 60-day survival rates between the mycophenolate mofetil and the
      combined groups (Fisher's exact; P=0.272, 0.518, 1.000, respectively). The sole
      adverse event observed in the mycophenolate mofetil group was diarrhoea (n=5).
      CLINICAL SIGNIFICANCE: Administration of mycophenolate mofetil appears safe in
      dogs with idiopathic immune-mediated haemolytic anaemia. The combination of
      glucocorticoids and mycophenolate mofetil has similar efficacy to alternate
      immunosuppressive protocols used to treat this disease.

PMID- 23879828
TI  - Refinement of the dose of doxapram to counteract the sedative effects of
      acepromazine in dogs.
AB  - OBJECTIVES: To evaluate the effectiveness of two doses of doxapram in reversing
      acepromazine sedation in dogs. METHODS: Using a crossover design, 10 adult mixed
      breed dogs received 0.05 mg/kg acepromazine, intramuscularly (im) followed 30
      minutes later by one of the three randomly determined treatments: 0.0625 mL/kg
      saline, intravenously (iv), 1.25 mg/kg doxapram, iv or 2.5 mg/kg doxapram, iv.
      Sedation scores were obtained by a single, blinded observer at 0, 15 and 30
      minutes after acepromazine administration and at 5, 15 and 30 minutes after the
      treatment administration. RESULTS: The mean baseline sedation score of all the
      treatments was not different among treatments. All the dogs had a significant
      increase in sedation score at 30 minutes after acepromazine administration. Both
      the low and high doses of doxapram showed a significant decrease in sedation
      score compared to saline, but there was no significant difference between the two
      doses. Five dogs in the high dose group panted after treatment injection, and
      this was significantly more than in the low dose group. CLINICAL SIGNIFICANCE:
      Doxapram is effective in reducing the sedative effects of acepromazine over a
      short period of time. A dose of 1.25 mg/kg effectively decreases acepromazine
      sedation without causing panting.

PMID- 23879829
TI  - Infectious agent screening in canine blood donors in the United Kingdom.
AB  - OBJECTIVES: Transfusion of blood products is an important component of veterinary
      emergency medicine. Donors must be carefully selected to minimise risk of
      transmission of blood-borne infectious agents. This study was devised to assess
      the prevalence of such agents in healthy, non-travelled UK dogs screened as
      prospective donors. METHODS: Ethylenediaminetetraacetic acid blood samples from
      dogs donating blood between August 2007 and January 2012 were screened by
      polymerase chain reaction for haemotropic mycoplasmas, Bartonella, Babesia,
      Leishmania, Ehrlichia and Anaplasma spp. Dogs with positive or inconclusive
      results underwent repeat polymerase chain reaction testing. RESULTS: Four of 262
      dogs had positive or inconclusive results at initial screening. Repeat polymerase
      chain reaction testing in each dog was negative, and none of the dogs developed
      clinical signs of disease. CLINICAL SIGNIFICANCE: The positive results on initial
      screening may have represented false positives from sample contamination or
      amplification of non-target DNA. It is also possible that dogs were infected at
      initial sampling but successfully cleared infection before repeat testing. The
      low number of positive results obtained suggests that prevalence of these agents
      in a population of healthy UK dogs is low and that use of blood products is
      unlikely to represent a significant risk of transmission of these diseases.

PMID- 23879831
TI  - Varieties of self-disturbance: a prism through which to view mental disorder.

PMID- 23879832
TI  - Early detection and intervention in psychiatry in the post-DSM-5 publication era:
      is it time to rethink the trees we bark up?

PMID- 23879833
TI  - Veteran mental health services in the UK: are we headed in the right direction?

PMID- 23879830
TI  - Metformin does not enhance insulin-stimulated vasodilation in skeletal muscle
      resistance arteries of the OLETF rat.
AB  - OBJECTIVE: To test the hypothesis that chronic metformin treatment enhances
      insulin-induced vasodilation in skeletal muscle resistance arteries and
      arterioles. METHODS: We assessed the effect of metformin treatment (from 20 to 32
      weeks of age) of obese Otsuka Long Evans Tokushima Fatty (OLETF) rats and lean
      LETO rats (300 mg/kg) on insulin-stimulated vasodilation in isolated skeletal
      muscle feed arteries and arterioles. RESULTS: Metformin treatment significantly
      lowered food intake, body weight, percent body fat, and HbA1c in OLETF rats.
      Metformin resulted in a ~30% reduction in insulin-induced vasodilation of soleus
      feed arteries (SFA) from OLETF rats. Inhibition of endothelin-1 (ET-1) signaling
      produced 20% dilation and eliminated the difference between metformin-treated and
      untreated OLETF rats in insulin-induced dilation of SFA. In contrast to the SFA,
      metformin did not alter insulin-stimulated vasodilation in gastrocnemius feed
      arteries (GFA), or second-order arterioles in the red (G2A-R) or white (G2A-W)
      portions of the gastrocnemius muscle of OLETF rats. Metformin had no effects on
      vasomotor responses of arteries from LETO. CONCLUSIONS: Although metformin exerts
      favorable effects on body composition and HbA1c, it does not enhance the
      vasodilatory responses to insulin in the skeletal muscle feed arteries or
      arterioles of the obese OLETF rat.

PMID- 23879834
TI  - Qualitative research on suicide in East Asia: a scoping review.
AB  - BACKGROUND: Suicide is a serious problem in East Asia. Yet, there is a
      significant lack of research on the topic, particularly using qualitative
      methodology. OBJECTIVES: This scoping review reports on findings drawn from 11
      qualitative studies, providing up-to-date knowledge and understandings about
      suicide in East Asian populations. METHODS: A web-based literature search was
      performed to identify empirical qualitative research articles addressing suicide
      in East Asia, published from January 2002 to December 2011. RESULTS: Three themes
      were identified within the reviewed studies; (1) influence of cultural beliefs;
      (2) the role of caregivers; and (3) specific sociological contexts. These themes
      are interrelated rather than mutually exclusive. CONCLUSION: The findings drawn
      from this scoping review reveal specific as well as broad contexts where suicidal
      ideation and behaviours occur among East Asians. To advance understandings,
      future studies should focus on comparative and longitudinal research to distil
      prevailing trends as well as the specificities that reside among particular East
      Asian subgroups (i.e. gender, sexual identity and generational) as a means to
      developing culturally sensitive and targeted suicide prevention programs.

PMID- 23879836
TI  - Transplanted induced pluripotent stem cells mitigate oxidative stress and improve
      cardiac function through the Akt cell survival pathway in diabetic
      cardiomyopathy.
AB  - Recent evidence suggests transplanted stem cells improve left ventricular
      function in diabetic induced cardiomyopathy (DICM). However, little is known
      about the mechanisms by which induced pluripotent stem (iPS) cells or factors
      released from these cells inhibit adverse cardiac remodeling in DICM. The present
      study was designed to determine molecular mediators and pathways regulated by
      transplanted iPS cells and their conditioned media (CM) in DICM. Animals were
      divided into four experimental groups such as control, streptozotocin (STZ),
      STZ+iPS-CM, and STZ+iPS cells. Experimental diabetes was induced in C57BL/6 mice
      by intraperitoneal STZ injections (100 mg/kg body weight for 2 consecutive days).
      Following STZ injections, iPS cells or CM was given intravenously for 3
      consecutive days. Animals were humanely killed, and hearts were harvested at D14.
      Animals transplanted with iPS cells or CM demonstrated a significant reduction in
      apoptosis, mediated by Akt upregulation and ERK1/2 downregulation, and inhibition
      of interstitial fibrosis via MMP-9 suppression compared with the STZ group.
      Oxidative stress was significantly hindered in iPS cell and CM groups as
      evidenced by diminished pro-oxidant expression and enhanced antioxidant (catalase
      and MnSOD) concentration. Echocardiography data suggest a significant improvement
      in cardiac function in cells and CM groups in comparison to STZ. In conclusion,
      our data strongly suggest that iPS cells and CM attenuate oxidative stress and
      associated apoptosis and fibrosis. Moreover, we also suggest that increased
      antioxidant levels, decreased adverse cardiac remodeling, and improved cardiac
      function is mediated by iPS CM and cells in DICM through multiple autocrine and
      paracrine mechanisms. 

PMID- 23879837
TI  - Quantitative measurement of pseudoexfoliation in the anterior segment of the eye
      performed in visible light.
AB  - INTRODUCTION: Pseudoexfoliation syndrome (PEX) is a systemic disease involving
      the accumulation of pathological material deposits in the tissues of the anterior
      segment of the eye. The problem of modern ophthalmology is a quantitative
      assessment of the severity of PEX in the diagnosis and evaluation of the
      treatment progress in patients. MATERIAL AND METHOD: For the purposes of this
      study, 52 images of the anterior segment of the eye with the resolution of M * N
      = 1280 * 960 pixels were obtained in jpg format using the slit lamp CSO 450-SL.
      The patients were aged 50-80 and were recruited from Poland. All patients who
      participated in the study provided written informed consent after explanation of
      the nature and possible consequences of the study. The image analysis method
      proposed by the authors contains the calculation of the direction field, setting
      a straight perpendicular line passing through each pixel of the edge of the
      pupil, the calculation of the intersection of straight lines in order to
      determine the central point of the pupil position, the detection of the contour
      of PEX and the outer border of the iris with the use of the polar coordinate
      system. All analyzed parameters were set automatically with one exception
      parameter chosen manually depending on the slit lamp type. RESULTS: A fully
      automatic measurement of PEX was carried out with the proposed method.
      Quantitative results enable to perform reproducible tests independently of the
      research centre. Owing to the image analysis method proposed by the authors, it
      is possible to obtain results in no more than 1 second on the Intel Core 2 Quad
      CPU 2.50 GHz with a measurement error below 3%. Other known methods of image
      analysis and processing that are compared in this paper give results with a
      greater error (4-35%) which depends on the degree of magnification (*6, *16, *20)
      and are not fully automatic. CONCLUSIONS: The methods of image analysis and
      processing enable a quantitative, repeatable and automatic measurement of the
      severity and progress of PEX syndrome. They support medical diagnosis and
      automatic archiving of results.

PMID- 23879838
TI  - Atrial fibrillation prevalence revisited.
AB  - BACKGROUND: The estimate of 0.4-1.0% prevalence of atrial fibrillation in the
      most recent American guidelines is based mainly on studies including patients
      with permanent atrial fibrillation (AF), although recent evidence shows that the
      stroke risk is similar with paroxysmal and persistent AF. Our objective was to
      determine the prevalence of AF in Sweden, irrespective of type and to what extent
      patients with AF receive adequate stroke prophylaxis. METHOD: Retrospective study
      of patients with a clinical diagnosis of atrial fibrillation between 2005 and
      2010 in the national Swedish Patient Register matched with data from the National
      Prescribed Drugs Register. RESULTS: We identified 307 476 individuals with a
      diagnosis of atrial fibrillation. Of these, 209 141 were still alive on the last
      day of the inclusion period, signifying a prevalence of clinically diagnosed AF
      in Sweden of 2.9% of the total adult (>=20 years) population. Only 42% of them
      had purchased an oral anticoagulant within 6 months of the first presentation
      with AF during the study period. Those at the highest risk of stroke were those
      least likely to receive anticoagulant treatment. Undertreatment was common
      amongst women and individuals >80 years, whilst overtreatment was common amongst
      young men without risk factors. CONCLUSION: The prevalence of atrial fibrillation
      is at least 2.9% of the Swedish adult population, not counting 'silent atrial
      fibrillation'. The official US figures probably underestimate the magnitude of
      the problem by a factor of 3-5. More than 80% had risk factors motivating
      anticoagulation therapy.

PMID- 23879839
TI  - Biophysical controls on cluster dynamics and architectural differentiation of
      microbial biofilms in contrasting flow environments.
AB  - Ecology, with a traditional focus on plants and animals, seeks to understand the
      mechanisms underlying structure and dynamics of communities. In microbial
      ecology, the focus is changing from planktonic communities to attached biofilms
      that dominate microbial life in numerous systems. Therefore, interest in the
      structure and function of biofilms is on the rise. Biofilms can form reproducible
      physical structures (i.e. architecture) at the millimetre-scale, which are
      central to their functioning. However, the spatial dynamics of the clusters
      conferring physical structure to biofilms remains often elusive. By experimenting
      with complex microbial communities forming biofilms in contrasting hydrodynamic
      microenvironments in stream mesocosms, we show that morphogenesis results in
      'ripple-like' and 'star-like' architectures--as they have also been reported from
      monospecies bacterial biofilms, for instance. To explore the potential
      contribution of demographic processes to these architectures, we propose a size
      structured population model to simulate the dynamics of biofilm growth and
      cluster size distribution. Our findings establish that basic physical and
      demographic processes are key forces that shape apparently universal biofilm
      architectures as they occur in diverse microbial but also in single-species
      bacterial biofilms.

PMID- 23879840
TI  - A bottom-up approach to build the hyperpolarizability of peptides and proteins
      from their amino acids.
AB  - We experimentally demonstrate that some peptides and proteins lend themselves to
      an elementary analysis where their first hyperpolarizability can be decomposed
      into the coherent superposition of the first hyperpolarizability of their
      elementary units. We then show that those elementary units can be associated with
      the amino acids themselves in the case of nonaromatic amino acids and nonresonant
      second harmonic generation. As a case study, this work investigates the
      experimentally determined first hyperpolarizability of rat tail Type I collagen
      and compares it to that of the shorter peptide [(PPG)10]3, where P and G are the
      one-letter code for Proline and Glycine, respectively, and that of the triamino
      acid peptides PPG and GGG. An absolute value of (0.16 +/- 0.01) * 10(-30) esu for
      the first hyperpolarizability of nonaromatic amino acids is then obtained by
      using the newly defined 0.087 * 10(-30) esu reference value for water. By using a
      collagen like model, the microscopic hyperpolarizability along the peptide bond
      can be evaluated at (0.7 +/- 0.1) * 10(-30) esu. 

PMID- 23879842
TI  - Evaluation of a point-of-care glucose and beta-hydroxybutyrate meter operated in
      various environmental conditions in prepartum and postpartum sheep.
AB  - OBJECTIVE: To compare beta-hydroxybutyrate (BHB) and glucose concentrations
      measured with a dual-purpose point-of-care (POC) meter designed for use in humans
      and a laboratory biochemical analyzer (LBA) to determine whether the POC meter
      would be reliable for on-farm measurement of blood glucose and BHB concentrations
      in sheep in various environmental conditions and nutritional states. ANIMALS: 36
      pregnant mixed-breed ewes involved in a maternal feed restriction study.
      PROCEDURES: Blood samples were collected from each sheep at multiple points
      throughout gestation and lactation to allow for tracking of gradually increasing
      metabolic hardship. Whole blood glucose and BHB concentrations were measured with
      the POC meter and compared with serum results obtained with an LBA. RESULTS: 464
      samples were collected. Whole blood BHB concentrations measured with the POC
      meter compared well with LBA results, and error grid analysis showed the POC
      values were acceptable. Whole blood glucose concentrations measured with the POC
      meter had more variation, compared with LBA values, over the glucose ranges
      evaluated. Results of error grid analysis of POC-measured glucose concentrations
      were not acceptable, indicating errors likely to result in needless treatment
      with glucose or other supplemental energy sources in normoglycemic sheep.
      CONCLUSIONS AND CLINICAL RELEVANCE: The POC meter was user-friendly and performed
      well across a wide range of conditions. The meter was adequate for detection of
      pregnancy toxemia in sheep via whole blood BHB concentration. Results should be
      interpreted with caution when the POC meter is used to measure blood glucose
      concentrations.

PMID- 23879843
TI  - Isolation rates of Campylobacter fetus subsp venerealis from bovine preputial
      samples via passive filtration on nonselective medium versus selective medium,
      with and without transport medium.
AB  - OBJECTIVE: To compare the recovery rates of Campylobacter fetus subsp venerealis
      (Cfv) from preputial scrapings of infected bulls with passive filtration on
      selective medium versus nonselective medium, with and without transport medium.
      SAMPLES: 217 preputial scrapings from 12 bulls (4 naturally and 8 artificially
      infected with Cfv). PROCEDURES: Preputial scrapings were collected in 2 mL of PBS
      solution and bacteriologically cultured directly on Skirrow medium or passively
      filtered through 0.65-MUm filters onto blood agar, with or without 24 hour
      preincubation in modified Weybridge transport enrichment medium (TEM). After 72
      hours, plates were examined for Cfv and bacterial and fungal contamination or
      overgrowth. RESULTS: Passive filtration of fresh preputial scrapings onto blood
      agar yielded significantly higher recovery rates of Cfv (86%) than direct plating
      on Skirrow medium (32%), whereas recovery from TEM was poor for both media (35%
      and 40%, respectively). Skirrow cultures without TEM were significantly more
      likely to have fungal contamination than were cultures performed with any other
      technique, and fungal contamination was virtually eliminated by passive
      filtration onto blood agar. Bacterial contamination by Pseudomonas spp was
      significantly more common with Skirrow medium versus passive filtration on blood
      agar, regardless of TEM use. CONCLUSIONS AND CLINICAL RELEVANCE: The use of
      transport medium and the choice of culture medium had significant effects on Cfv
      recovery and culture contamination rates from clinical samples. Both factors
      should be considered when animals are tested for this pathogen.

PMID- 23879844
TI  - Effects of ketamine, propofol, or thiopental administration on intraocular
      pressure and qualities of induction of and recovery from anesthesia in horses.
AB  - OBJECTIVE: To assess the effects of ketamine hydrochloride, propofol, or
      compounded thiopental sodium administration on intraocular pressure (IOP) and
      qualities of induction of and recovery from anesthesia in horses. ANIMALS: 6
      healthy adult horses. PROCEDURES: Horses were sedated with xylazine hydrochloride
      (0.5 mg/kg), and anesthesia was induced with guaifenesin followed by ketamine (2
      mg/kg), propofol (3 mg/kg), or thiopental (4 mg/kg) in a crossover study with >=
      1 week between treatments. For each horse, IOP in the right eye was measured with
      a handheld applanation tonometer before and after xylazine administration, at the
      time of recumbency, and every 3 minutes after induction of anesthesia until
      spontaneous movement was observed. Cardiorespiratory responses and venous blood
      measurements were recorded during anesthesia. Induction of and recovery from
      anesthesia were subjectively evaluated by investigators who were unaware of the
      anesthetic treatment of each horse. Data were analyzed via a repeated-measures
      ANOVA with Holm-Sidak post hoc comparisons. RESULTS: Compared with findings after
      xylazine administration (mean +/- SD, 17 +/- 3 mm Hg), thiopental decreased IOP
      by 4 +/- 23%, whereas propofol and ketamine increased IOP by 8 +/- 11% and 37 +/-
      16%, respectively. Compared with the effects of ketamine, propofol and thiopental
      resulted in significantly lower IOP at the time of recumbency and higher heart
      rates at 3 minutes after induction of anesthesia. No other significant
      differences among treatments were found. CONCLUSIONS AND CLINICAL RELEVANCE:
      These findings support the use of thiopental or propofol in preference to
      ketamine for horses in which increases in IOP should be minimized.

PMID- 23879845
TI  - Effects of subtherapeutic concentrations of antimicrobials on gene acquisition
      events in Yersinia, Proteus, Shigella, and Salmonella recipient organisms in
      isolated ligated intestinal loops of swine.
AB  - OBJECTIVE: To assess antimicrobial resistance and transfer of virulence genes
      facilitated by subtherapeutic concentrations of antimicrobials in swine
      intestines. ANIMALS: 20 anesthetized pigs experimentally inoculated with donor
      and recipient bacteria. PROCEDURES: 4 recipient pathogenic bacteria (Salmonella
      enterica serotype Typhimurium, Yersinia enterocolitica, Shigella flexneri, or
      Proteus mirabilis) were incubated with donor bacteria in the presence of
      subinhibitory concentrations of 1 of 16 antimicrobials in isolated ligated
      intestinal loops in swine. Donor Escherichia coli contained transferrable
      antimicrobial resistance or virulence genes. After coincubations, intestinal
      contents were removed and assessed for pathogens that acquired new antimicrobial
      resistance or virulence genes following exposure to the subtherapeutic
      concentrations of antimicrobials. RESULTS: 3 antimicrobials (apramycin,
      lincomycin, and neomycin) enhanced transfer of an antimicrobial resistance
      plasmid from commensal E coli organisms to Yersinia and Proteus organisms,
      whereas 7 antimicrobials (florfenicol, hygromycin, penicillin G, roxarsone,
      sulfamethazine, tetracycline, and tylosin) exacerbated transfer of an integron
      (Salmonella genomic island 1) from Salmonella organisms to Yersinia organisms.
      Sulfamethazine induced the transfer of Salmonella pathogenicity island 1 from
      pathogenic to nonpathogenic Salmonella organisms. Six antimicrobials (bacitracin,
      carbadox, erythromycin, sulfathiazole, tiamulin, and virginiamycin) did not
      mediate any transfer events. Sulfamethazine was the only antimicrobial implicated
      in 2 types of transfer events. CONCLUSIONS AND CLINICAL RELEVANCE: 10 of 16
      antimicrobials at subinhibitory or subtherapeutic concentrations augmented
      specific antimicrobial resistance or transfer of virulence genes into pathogenic
      bacteria in isolated intestinal loops in swine. Use of subtherapeutic
      antimicrobials in animal feed may be associated with unwanted collateral effects.

PMID- 23879846
TI  - Effect of furosemide and high-dosage pimobendan administration on the renin
      angiotensin-aldosterone system in dogs.
AB  - OBJECTIVE: To determine whether a high dosage of pimobendan, when administered
      concurrently with moderate-dosage furosemide to healthy dogs, would activate the
      renin-angiotensin-aldosterone system (RAAS) more than furosemide alone. ANIMALS:
      12 healthy dogs. PROCEDURES: 6 dogs received furosemide (2.0 mg/kg, PO, q 12 h)
      only, as an RAAS activator, for 10 days. The other 6 dogs received furosemide
      (2.0 mg/kg, PO, q 12 h) and pimobendan (0.6 mg/kg, PO, q 12 h) for 10 days. The
      effect of these drugs on the RAAS was determined by measurement of the
      aldosterone-to-creatinine ratio (A:C) in urine collected in the morning and
      evening of study days -2, -1, 1, 5, and 10. RESULTS: Although there was an
      increase in the urine A:C during the study period in both groups, it was
      significant only for dogs that received both drugs. The urine A:C only differed
      significantly between groups on day 1, at which time A:C was greater in the group
      that received both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: High-dosage
      pimobendan administration neither substantially suppressed nor potentiated the
      RAAS when administered with furosemide in healthy dogs.

PMID- 23879848
TI  - In vivo and in vitro evaluation of the effects of domperidone on the
      gastrointestinal tract of healthy horses.
AB  - OBJECTIVE: To determine the effects of domperidone on in vivo and in vitro
      measures of gastrointestinal tract motility and contractility in healthy horses.
      SAMPLE: 18 adult horses and tissue samples from an additional 26 adult horses.
      PROCEDURES: Domperidone or placebo paste was administered to healthy horses in a
      2-period crossover study. Gastric emptying was evaluated after oral
      administration of domperidone paste (1.1 or 5.0 mg/kg) or placebo paste by means
      of the acetaminophen absorption test in 12 horses. Frequency of defecation,
      weight of feces produced, fecal moisture, and stomach-to-anus transit time of
      microspheres were evaluated after administration of domperidone paste (1.1 mg/kg)
      or placebo paste in 6 horses. The effect of domperidone on smooth muscle
      contractile activity in samples of duodenum, jejunum, ileum, or colon obtained
      from 26 horses immediately after euthanasia (for nonsystemic medical problems)
      was investigated. RESULTS: Oral administration of 5.0 mg of domperidone/kg
      increased peak plasma acetaminophen concentration and area under the curve,
      indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg
      had no effect on gastric emptying, transit time, defecation frequency, or amount
      and moisture of excreted feces. Contractile activities of circular and
      longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not
      altered by domperidone. Dopamine increased contractile activity of longitudinal
      muscle strips but not that of circular muscle strips from the midjejunum.
      Domperidone decreased the dopamine-induced contractile activity of midjejunal
      longitudinal muscle strips. CONCLUSIONS AND CLINICAL RELEVANCE: The potential
      beneficial effects of domperidone in horses with ileus need to be evaluated in
      horses with decreased gastric emptying or adynamic ileus.

PMID- 23879847
TI  - Comparison of two analyzers for measurement of plasma total carbon dioxide
      concentration in horses.
AB  - OBJECTIVE: To determine the degree of agreement between 2 analyzers for
      measurement of total CO2 concentration (ctCO2) in equine plasma. ANIMALS: 6
      healthy untrained horses, 6 trained Standardbreds undergoing a simulated race
      protocol, and 135 trained Standardbreds at a racetrack. PROCEDURES: Jugular
      venous blood samples were obtained from all horses. Two analyzers (commonly used
      analyzer A and less expensive analyzer B) were used to measure plasma ctCO2 in
      each sample. Validation of both analyzers was conducted in accordance with
      guidelines established by the Clinical and Laboratory Standards Institute and
      involved characterization of linearity, total analytic error, and bias
      estimation. RESULTS: Total analytic error (instrument SD) was 0.58 mmol/L
      (coefficient of variation, 1.6%) and 0.49 mmol/L (coefficient of variation, 1.4%)
      for analyzers A and B, respectively, when measuring an aqueous standard
      containing 36.0 mmol of CO2/L. A 1 g/L decrease in plasma protein concentration
      corresponded to an increase in ctCO2 measured with analyzer B of 0.065 mmol/L. A
      difference plot indicated that analyzer B produced values 2.7% higher than
      analyzer A for 103 samples from the 6 trained and exercised Standardbreds (mean
      plasma protein concentration, 67 g/L). CONCLUSIONS AND CLINICAL RELEVANCE:
      Analyzer B provided adequate precision and linearity for measurement of ctCO2
      from 5 to 40 mmol/L and was therefore suitable for measuring ctCO2 in equine
      plasma, provided allowances are made for changes in plasma protein concentration.

PMID- 23879849
TI  - Effect of treatment with simvastatin and cyclosporine on neurotransmitter
      concentrations in cerebrospinal fluid after subarachnoid hemorrhage in dogs.
AB  - OBJECTIVE: To measure concentrations of glutamate, aspartate, gamma-aminobutyric
      acid (GABA), and glycine in CSF of dogs with experimentally induced subarachnoid
      hemorrhage (SAH) and to assess effects of cyclosporine and simvastatin on these
      concentrations. SAMPLE: CSF samples from 13 dogs. PROCEDURES: In a previous
      study, SAH was induced in dogs via 2 injections of autologous blood into the
      cerebellomedullary cistern 24 hours apart. Dogs were untreated (control; n = 5)
      or received simvastatin alone (4) or simvastatin in combination with cyclosporine
      (4). Samples of CSF were collected before the first blood injection (baseline;
      time 0), before the second blood injection, and on days 3, 7, and 10. For the
      study reported here, neurotransmitter concentrations in CSF were analyzed via
      high-performance liquid chromatography. Data were analyzed with a repeated
      measures model with adjustments for multiple comparisons by use of the Tukey
      method. RESULTS: In control dogs, the glutamate concentration peaked on day 3 and
      there was a significant increase in GABA and glutamate concentrations. Glutamate
      concentrations were significantly lower and glycine concentrations significantly
      higher on day 3 after administration of simvastatin alone or simvastatin in
      combination with cyclosporine, compared with concentrations for the control
      group. No significant differences in GABA and aspartate concentrations were
      detected among treatment groups at any time point. CONCLUSIONS AND CLINICAL
      RELEVANCE: Glutamate concentrations were increased in the CSF of dogs with SAH.
      Simvastatin administration attenuated high glutamate concentrations. A
      combination of immunosuppression and upregulation of nitric oxide synthase may be
      useful in lowering high glutamate concentrations in ischemic CNS conditions.

PMID- 23879850
TI  - Comparison of concentrations of gamma-aminobutyric acid and glutamate in
      cerebrospinal fluid of dogs with idiopathic epilepsy with and without seizure
      related magnetic resonance imaging hyperintense areas in the limbic system.
AB  - OBJECTIVE: To investigate differences in CSF concentrations of excitatory and
      inhibitory neurotransmitters in dogs with and without T2-weighted (T2W) MRI
      hyperintense areas in the limbic system. SAMPLE: Archived CSF samples and stored
      brain MRI images of 5 healthy research dogs (group 1), 8 dogs with idiopathic
      epilepsy (IE) with no abnormal MRI findings (group 2), and 4 dogs with IE with
      hyperintense areas in the limbic system detected by means of T2W MRI (group 3).
      PROCEDURES: Archived CSF samples and stored MRI images obtained from all dogs
      were evaluated. Dogs in groups 2 and 3 were matched on the basis of age and
      breed. High-performance liquid chromatography was used to evaluate glutamate and
      gamma-aminobutyric acid (GABA) concentrations in CSF samples. RESULTS: Glutamate
      concentrations were higher in CSF of both groups of dogs with IE than in healthy
      dogs. However, glutamate concentrations in CSF were not significantly higher in
      dogs with IE and with hyperintense areas than in dogs with IE but no abnormal MRI
      findings. Concentrations of GABA in CSF were higher in group 3 than in group 2
      and in group 2 than in group 1. CONCLUSIONS AND CLINICAL RELEVANCE: No
      significant difference was evident between glutamate concentrations in CSF of
      dogs with IE and with and without hyperintense areas detected by means of T2W
      MRI. However, glutamate concentrations typically were higher in CSF of dogs with
      IE and MRI hyperintense areas. Future studies with larger sample sizes should be
      conducted to confirm this finding and to determine the clinical importance of
      high glutamate concentrations in CSF of dogs with IE.

PMID- 23879851
TI  - Effects of peribulbar anesthesia (sub-Tenon injection of a local anesthetic) on
      akinesia of extraocular muscles, mydriasis, and intraoperative and postoperative
      analgesia in dogs undergoing phacoemulsification.
AB  - OBJECTIVE: To evaluate the effects of peribulbar anesthesia (sub-Tenon injection
      of lidocaine hydrochloride) on akinesia of extraocular muscles, mydriasis, and
      intraoperative and postoperative analgesia in dogs undergoing
      phacoemulsification. ANIMALS: 14 Beagles with ophthalmically normal eyes.
      PROCEDURES: A blinded randomized controlled trial was performed. Dogs were
      anesthetized and assigned to 2 treatments: concurrent sub-Tenon injection of 2%
      lidocaine hydrochloride solution (2 mL) and IV injection of saline (0.9% NaCl)
      solution (0.02 mL/kg; lidocaine group [n = 7]) or concurrent sub-Tenon injection
      of saline solution (2 mL) and IV injection of 0.2 mg of atracurium/kg (0.02
      mL/kg; control group [7]). Pupils were dilated by topical application of a
      combined tropicamide and phenylephrine ophthalmic solution. Ten minutes after the
      injections, pupil diameter was measured and phacoemulsification was performed.
      End-tidal isoflurane concentration was used to evaluate intraoperative pain.
      Subjective pain scores were recorded during the postoperative period. RESULTS:
      Akinesia was induced and maintained throughout the surgery in all eyes. Mean +/-
      SD pupil diameter was significantly greater in the lidocaine group (13.7 +/- 0.7
      mm) than in the control group (12.2 +/- 0.8 mm). Isoflurane requirements were
      significantly lower in the lidocaine group than the control group. However,
      postoperative pain scores were not significantly different between the groups.
      CONCLUSIONS AND CLINICAL RELEVANCE: Sub-Tenon injection of lidocaine was an
      effective method for inducing akinesia of extraocular muscles, mydriasis, and
      intraoperative analgesia for phacoemulsification in dogs. Therefore, this could
      be another option for surgical field exposure and pain management during
      phacoemulsification in dogs.

PMID- 23879852
TI  - Effect of hydroxyethyl starch 130/0.4 and 200/0.5 solutions on canine platelet
      function in vitro.
AB  - OBJECTIVE: To determine whether dilution of blood samples from healthy dogs with
      2 hydroxyethyl starch (HES) solutions, HES 130/0.4 and HES 200/0.5, would result
      in platelet dysfunction as measured by closure time (Ct) beyond a dilutional
      effect. SAMPLE: Citrated blood samples from 10 healthy dogs with a Ct within
      reference limits (52 to 86 seconds). PROCEDURES: Blood samples were diluted 1:9
      and 1:3 with 6% HES 130/0.4 and 10% HES 200/0.5 solutions and saline (0.9% NaCl)
      solution. Dilutions at 1:9 and 1:3 mimicked 10 mL/kg and 30 mL/kg doses,
      respectively, ignoring in vivo redistribution. Closure time was measured with a
      platelet function analyzer and compared among dilutions. RESULTS: A dilutional
      effect on Ct was evident for the 1:3 dilution, compared with the 1:9 dilution,
      but only HES 200/0.5 increased the Ct beyond the dilutional effect at the 1:3
      dilution, to a median Ct of 125 seconds (interquartile range, 117.5 to 139.5
      seconds). No effect of HES or dilution on Ct was identified at the 1:9 dilution.
      CONCLUSIONS AND CLINICAL RELEVANCE: 1:3 dilution of blood samples from healthy
      dogs with HES 200/0.5 but not HES 130/0.4 significantly increased Ct beyond the
      dilutional effect, suggesting that IV administration of HES 200/0.5 in dogs might
      cause platelet dysfunction.

PMID- 23879853
TI  - Evaluation of serosal patch supplementation of surgical anastomoses in intestinal
      segments from canine cadavers.
AB  - OBJECTIVE: To compare leakage and maximum intraluminal pressures of intestinal
      anastomoses with and without serosal patch supplementation in dogs. SAMPLE:
      Healthy small intestine segments from cadavers of 2 dogs euthanized for reasons
      unrelated to the study. PROCEDURES: 12 enterectomy constructs were created by
      anastomosis of intestinal segments with a standard simple continuous suture
      pattern. Half of the constructs were randomly selected for additional serosal
      patch support. Leakage and maximum intraluminal pressures were measured in and
      compared between patch-supplemented and nonsupplemented constructs. RESULTS: Mean
      +/- SD leakage pressure was significantly greater for the patch-supplemented
      anastomoses (81.8 +/- 6.7 mm Hg) than for the nonsupplemented anastomoses (28.0
      +/- 6.7 mm Hg). Maximum intraluminal pressures were not significantly different
      between the groups. CONCLUSIONS AND CLINICAL RELEVANCE: Serosal patch
      supplemented anastomoses were able to sustain a significantly higher pressure
      before leakage than were nonsupplemented anastomoses in intestinal specimens from
      canine cadavers. The serosal patch supplementation may protect against leakage
      immediately after enterectomy in dogs.

PMID- 23879854
TI  - Which aspects of an oral health-related quality of life measure are mainly
      associated with global ratings of oral health in children?
AB  - OBJECTIVES: To assess the associations of global subjective ratings of oral
      health with different aspects of an oral health-related quality of life measure,
      namely total Oral Impacts on Daily Performances (OIDP) and Child-Oral Impacts on
      Daily Performances (Child-OIDP) scores, extent and intensity of oral impacts, the
      different performance scores and oral impacts attributed to certain groups of
      oral conditions. METHODS: This study was part of the Sixth Thailand National Oral
      Health Survey. One thousand and sixty-six 12-year-olds and 815 15-year-olds were
      interviewed on their OHRQoL using Child-OIDP and OIDP indices, respectively, and
      rated their overall oral problems on 3-point and 5-point scales, respectively.
      Associations of global rating of oral health with different Child-OIDP/OIDP
      outcome variables were estimated using Spearman's rank correlations and logistic
      regressions. RESULTS: Child-OIDP/OIDP scores were significantly associated with
      global ratings. Intensity was associated with global ratings, whereas extent was
      not. Impacts of 'very little' intensity were associated with a slightly higher
      chance of having poorer oral health perceptions. Global ratings were associated
      most with oral impacts attributed to dental caries, but not with the impacts
      related to natural process, such as eruption. Eating, cleaning teeth, emotional
      stability and smiling, plus social contact in 15-year-olds were performances
      associated with global ratings. Fifteen-year-old girls were more likely to
      perceive more oral problems than boys. CONCLUSIONS: Associations of global
      ratings of oral health with Child-OIDP/OIDP scores were mainly due to the
      intensity of impacts. Global ratings were related to multidimensional aspects of
      children's quality of life.

PMID- 23879855
TI  - Hospitalization of patients with schizophrenic and affective disorders in Israel
      in the aftermath of the structural and rehabilitation reforms.
AB  - BACKGROUND: In the last decade (2001-2010) the Ministry of Health implemented two
      major inter-related reforms: a 'structural reform' to reduce the number of
      psychiatric beds and the 'Rehabilitation of the Mentally Disabled in the
      Community Law', which allocated funds for a variety of residential and vocational
      programs in the community for these patients. The objective of the present paper
      was to examine the impact of the two reforms on the hospitalization of
      schizophrenic and affective disorder patients by tracking the patterns of their
      inpatient care during the last decade. METHODS: Data on all psychiatric
      admissions during the period 1990-2011 were extracted from the Israel Psychiatric
      Case Register to examine changes in the rate of admissions, length of
      hospitalizations, total inpatient days and tenure in the community. The analysis
      was done separately for first-in-life vs. all admissions and for patients with
      schizophrenia vs. patients with affective disorders. RESULTS: From 2006 onward,
      with no decrease in the number the beds, the number of inpatient days for first
      in-life patients with schizophrenia decreased by 29%, their admission rates
      dropped by 22%, the proportion of short [< 30 days] first in life episodes went
      up, while the percentage of those whose first in life episode lasted more than
      one year went down from 2.5% to 0.5%. The parallel results for patients with
      affective disorders were much less significant. CONCLUSIONS: An increasing
      percentage of patients with schizophrenia are not admitted to psychiatric wards
      at all and an increasing percentage of those who are admitted are treated during
      a shorter episode. The change is probably due to the rehabilitation reform which
      enabled the structural reform (the reduction in beds) to be implemented
      effectively.

PMID- 23879856
TI  - The relationship between water temperature and the development cycle beginning
      and duration in three black fly species.
AB  - Understanding environmental factors affecting the timing and rate of animal
      development, as well as the factors that cause their effects, is of great
      importance. The purpose of this study was to establish the relationship between
      the onset and duration of the development from egg to pupal stage and water
      temperature in three black fly (Diptera: Simuliidae) species: Simulium (Simulium)
      reptans (Linnaeus 1758), Simulium (Byssodon) maculatum (Meigen 1804), Simulium
      (Boophthora) erythrocephalum (De Geer 1776). The study was based on surveys
      conducted between April and June of 1998-2010. The water temperature on the day
      of larval eclosion had no statistically significant impact on the beginning of
      development in any of the three species studied. The date when water temperature
      in the river reaches a certain value is important to the initiation of
      development in some black fly species. The present study revealed that the most
      important dates to the beginning of development of S. reptans black flies are
      when water temperature rises above 5 degrees  C, 7 degrees  C, and 10 degrees  C,
      while pivotal dates to the development of S. maculatum are when water temperature
      exceeds 4 degrees  C and 10 degrees  C. Water temperature most often exceeds the
      value important to the start of the development of these black fly species during
      March and April. The findings of the present study show that the hatching time of
      the two black fly species is also related to the mean water temperature in March
      and April. There were no statistically significant relations established between
      certain temperature dates and the beginning of larval development in S.
      erythrocephalum. Significant relations (p < 0.01) were found to exist between the
      duration of the development cycle from the first instar larva to pupa and the
      mean water temperature during the development period in S. reptans (r = -0.84; y
      = 53.088e(-0.0806x), R(2) = 0.70), S. maculatum (r = -0.82; y = 186.48e(
      0.1123x), R(2) = 0.69) and S. erythrocephalum (r = -0.83; y = 58.768e(-0.0652x),
      R(2) = 0.70). The present study showed that the duration of development from the
      first instar larva to pupa in all the three black fly species studied was shorter
      when water temperatures during the development period were higher and longer when
      water temperatures were lower. The devised model of dependence between the
      duration of the studied black fly species' development and water temperature was
      verified experimentally.

PMID- 23879857
TI  - Long-Term Follow-Up of UCLP Patients: Surgical and Orthodontic Burden of Care
      During Growth and Final Orthognathic Surgery Need.
AB  - OBJECTIVE: The goal of this study was to evaluate the craniofacial morphology at
      5 and 10 years of age and at the completion of growth, the need for final
      orthognathic surgery, and the orthodontic burden in a sample of patients with
      unilateral cleft lip and palate consecutively treated by the same surgeon with
      the same two-step protocol. DESIGN: A sample of 62 adult patients with unilateral
      cleft lip and palate was retrospectively collected (mean age, 17.5 years).
      Lateral cephalograms at three time points were traced. The need for orthognathic
      surgery was assessed, subdividing the sample into an orthognathic surgery group
      and nonorthognathic surgery group. Time and modality of orthodontic treatment
      were recorded. RESULTS: Cephalometric values related to maxillary growth (SNA,
      SNAns) and maxillomandibular relation (ANB, NAPg) were significantly different
      between the two groups already at 5 and 10 years of age. All patients presenting
      an ANB smaller than 2 degrees  at 5 years needed a Le Fort I osteotomy.
      Mandibular protrusion (SNB, SNPg) was not different at 5 and 10 years, but was
      different at the completion of growth. Patients with the same initial
      maxillomandibular relation did not show better growth when subjected to earlier
      or longer orthodontic treatment. CONCLUSION: Patients needing final jaw surgery
      had a more severe skeletal discrepancy during early childhood. The ANB angle at 5
      years allowed doctors to identify 45% of the need for orthognathic surgery. The
      final craniofacial pattern does not seem to change significantly with early or
      prolonged orthodontic treatment.

PMID- 23879858
TI  - Tissue-engineered oral mucosa for mucosal reconstruction in a pediatric patient
      with hemifacial microsomia and ankyloglossia.
AB  - Many types of soft tissue grafts have been used for the reconstruction of oral
      mucosal defects. The best results are achieved with mucosal grafts; however, when
      large areas must be grafted, sufficient donor tissue is not available. Tissue
      engineering represents an alternative method to obtain sufficient autologous
      tissue for reconstructing oral wounds. Herein we present a pediatric patient with
      hemifacial microsomia and congenital ankyloglossia requiring multiple surgical
      interventions, and in which an autologous full-thickness tissue-engineered oral
      mucosa was used for successful oral reconstruction. Our study demonstrates that
      even under challenging conditions, robust tissue-engineered products, such as the
      fibrin-based oral mucosa described here, can achieve successful tissue
      regeneration. 

PMID- 23879859
TI  - Tunable heparan sulfate mimetics for modulating chemokine activity.
AB  - Heparan sulfate (HS) glycosaminoglycans participate in critical biological
      processes by modulating the activity of a diverse set of protein binding
      partners. Such proteins include all known members of the chemokine superfamily,
      which are thought to guide the migration of immune cells through their
      interactions with HS. Here, we describe an expedient, divergent synthesis to
      prepare defined HS glycomimetics that recapitulate the overall structure and
      activity of HS glycosaminoglycans. Our approach uses a core disaccharide
      precursor to produce a variety of differentially sulfated glycopolymers. We
      demonstrate that a specific trisulfated mimetic antagonizes the chemotactic
      activity of the proinflammatory chemokine RANTES with potency similar to that of
      heparin, without inhibiting serine proteases in the blood coagulation cascade.
      Our work provides a general strategy for modulating chemokine activity and
      dissecting the pleiotropic functions of HS/heparin through the presentation of
      defined sulfation motifs within polymeric scaffolds. 

PMID- 23879860
TI  - Development of a volumetric projection technique for the digital evaluation of
      field of view.
AB  - Current regulations for field of view requirements in road vehicles are defined
      by 2D areas projected on the ground plane. This paper discusses the development
      of a new software-based volumetric field of view projection tool and its
      implementation within an existing digital human modelling system. In addition,
      the exploitation of this new tool is highlighted through its use in a UK
      Department for Transport funded research project exploring the current concerns
      with driver vision. Focusing specifically on rearwards visibility in small and
      medium passenger vehicles, the volumetric approach is shown to provide a number
      of distinct advantages. The ability to explore multiple projections of both
      direct vision (through windows) and indirect vision (through mirrors) provides a
      greater understanding of the field of view environment afforded to the driver
      whilst still maintaining compatibility with the 2D projections of the regulatory
      standards. PRACTITIONER SUMMARY: Field of view requirements for drivers of road
      vehicles are defined by simplified 2D areas projected onto the ground plane.
      However, driver vision is a complex 3D problem. This paper presents the
      development of a new software-based 3D volumetric projection technique and its
      implementation in the evaluation of driver vision in small- and medium-sized
      passenger vehicles.

PMID- 23879861
TI  - Isolation, characterization, and transplantation of bone marrow-derived cell
      components with hematopoietic stem cell niche properties.
AB  - Although the unique role of hematopoietic stem cell (HSC) niche in hematopoiesis
      has long been recognized, unsuccessful isolation of intact niche units limited
      their in vitro study, manipulation, and therapeutic application. Here, we
      isolated cell complexes based on size fractionation from mouse bone marrow (BM),
      characterized the derived cells, and transplanted them to irradiated mice. These
      cell complexes were the origin of both BM mesenchymal stem cells and various
      hematopoietic lineages when kept in appropriate culture conditions. They also had
      the potential of recruiting circulating HSC. Intraperitoneal transplantation of
      these structures into irradiated mice not only showed long-lasting hematopoietic
      multilineage reconstitution, but also could recover the stromal cells of BM. In
      conclusion, this study for the first time provides evidences on the feasibility
      and efficacy of transplantation of HSC in association with their native
      specialized microenvironment. As the molecular cross-talk between HSC and niche
      is crucial for their proper function, the proposed method could be considered as
      a novel hematopoietic transplantation strategy. 

PMID- 23879862
TI  - Factors associated with survival in 148 recumbent horses.
AB  - REASONS FOR PERFORMING STUDY: There are currently few data available on the
      prognosis and outcome of recumbent horses. OBJECTIVES: To investigate the outcome
      of hospitalised horses that had been recumbent in the field or hospital and
      factors affecting their survival within the first 3 days of hospitalisation and
      survival after 3 days to hospital discharge. STUDY DESIGN: Retrospective analysis
      of clinical records. METHODS: Records of 148 horses admitted to the William R.
      Pritchard Veterinary Medical Teaching Hospital, University of California Davis
      from January 1995 to December 2010 with a history of recumbency or horses that
      became recumbent while hospitalised were evaluated. Exact logistic regression was
      used to assess the association between clinical parameters and survival within
      the first 3 days of hospitalisation and survival to hospital discharge after 3
      days. RESULTS: There were 109 nonsurvivors and 39 survivors. Multivariate
      analysis showed variables associated with an increased odds of death within the
      first 3 days of hospitalisation included duration of clinical signs prior to
      presentation, with horses showing clinical signs for over 24 h having increased
      odds of death (P = 0.043, odds ratio [OR] 4.16, 95% confidence interval [95% CI]
      1.04-16.59), the presence of band neutrophils (P = 0.02, OR 7.94, 95% CI 1.39
      45.46), the horse not using the sling (P = 0.031, OR 4.22, 95% confidence
      interval 1.14-15.68) and horses that were unable to stand after treatment
      (P<0.0001, OR 231.15, 95% CI 22.82-2341.33). Increasing cost was associated with
      lower odds of death (P = 0.017, OR 0.96, for each additional $100 billed, 95% CI
      0.93-0.99). CONCLUSIONS: This study demonstrates that the duration of clinical
      signs, response to treatment and the ability of horses to use a sling are
      associated with survival to hospital discharge for recumbent horses.

PMID- 23879863
TI  - In-source decay during matrix-assisted laser desorption/ionization combined with
      the collisional process in an FTICR mass spectrometer.
AB  - The type of ions detected after in-source decay (ISD) in a MALDI source differs
      according to the ion source pressure and on the mass analyzer used. We present
      the mechanism leading to the final ISD ions for a Fourier transform-ion cyclotron
      resonance mass spectrometer (FTICR MS). The MALDI ion source was operated at
      intermediate pressure to cool the resulting ions and increase their lifetime
      during the long residence times in the FTICR ion optics. This condition produces
      not only c', z', and w fragments, but also a, y', and d fragments. In particular,
      d ions help to identify isobaric amino acid residues present near the N-terminal
      amino acid. Desorbed ions collide with background gas during desorption, leading
      to proton mobilization from Arg residues to a less favored protonation site. As a
      result, in the case of ISD with MALDI FTICR, the influence of the Arg residue in
      ISD fragmentation is less straightforward than for TOF MS and the sequence
      coverage is thus improved. MALDI-ISD combined with FTICR MS appears to be a
      useful method for sequencing of peptides and proteins including discrimination of
      isobaric amino acid residues and site determination of phosphorylation.
      Additionally we also used new software for in silico elimination of MALDI matrix
      peaks from MALDI-ISD FTICR mass spectra. The combination of high resolving power
      of an FTICR analyzer and matrix subtraction software helps to interpret the low
      m/z region of MALDI-ISD spectra. Finally, several of these developed methods are
      applied in unison toward a MALDI ISD FTICR imaging experiment on mouse brain to
      achieve better results. 

PMID- 23879864
TI  - Histologic changes in basal cell carcinoma after treatment with vismodegib.

PMID- 23879865
TI  - Five phylogenetically close rice SWEET genes confer TAL effector-mediated
      susceptibility to Xanthomonas oryzae pv. oryzae.
AB  - Bacterial plant-pathogenic Xanthomonas strains translocate transcription
      activator-like (TAL) effectors into plant cells to function as specific
      transcription factors. Only a few plant target genes of TAL effectors have been
      identified, so far. Three plant SWEET genes encoding putative sugar transporters
      are known to be induced by TAL effectors from rice-pathogenic Xanthomonas oryzae
      pv. oryzae (Xoo). We predict and validate that expression of OsSWEET14 is induced
      by a novel TAL effector, Tal5, from an African Xoo strain. Artificial TAL
      effectors (ArtTALs) were constructed to individually target 20 SWEET orthologs in
      rice. They were used as designer virulence factors to study which rice SWEET
      genes can support Xoo virulence. The Tal5 target box differs from those of the
      already known TAL effectors TalC, AvrXa7 and PthXo3, which also induce expression
      of OsSWEET14, suggesting evolutionary convergence on key targets. ArtTALs
      efficiently complemented an Xoo talC mutant, demonstrating that specific
      induction of OsSWEET14 is the key target of TalC. ArtTALs that specifically
      target individual members of the rice SWEET family revealed three known and two
      novel SWEET genes to support bacterial virulence. Our results demonstrate that
      five phylogenetically close SWEET proteins, which presumably act as sucrose
      transporters, can support Xoo virulence. 

PMID- 23879867
TI  - How composition methods are developed and validated.
AB  - Method validation is a critical prerequisite to performing analytical methods in
      the laboratory. A given analytical method is validated for a specific matrix or
      matrices. If the matrix to be tested is not included in the original scope of
      method validation, a validation must be performed to determine if the method is
      applicable to that particular matrix. A number of organizations, such as AOAC and
      ISO, publish peer-reviewed methods for cross-industry matrices, whereas others,
      such as AOCS and AACC, are focused on specific industry segments (fats/oils and
      cereal grains). When no validated method is available for the analyte of
      interest, method development and validation must first be performed to ensure
      that correct identification and quantification of the analyte are being observed
      and measured. Development of a new method requires an understanding of the
      chemistry and properties of the analyte to be tested, as well as the various
      types of instrumentation currently available. Method development and improvement
      is a continuous process, as technology advances and new instrumentation and
      techniques become available. This paper addresses some of the decisions related
      to method development but will primarily focus on validation as it applies to
      compositional testing of foods, crops, and commodities, the factors that
      determine method selection, and how extensive the validation need be. 

PMID- 23879866
TI  - Factor VII and protein C are phosphatidic acid-binding proteins.
AB  - Seven proteins in the human blood clotting cascade bind, via their GLA (gamma
      carboxyglutamate-rich) domains, to membranes containing exposed
      phosphatidylserine (PS), although with membrane binding affinities that vary by 3
      orders of magnitude. Here we employed nanodiscs of defined phospholipid
      composition to quantify the phospholipid binding specificities of these seven
      clotting proteins. All bound preferentially to nanobilayers in which PS
      headgroups contained l-serine versus d-serine. Surprisingly, however,
      nanobilayers containing phosphatidic acid (PA) bound substantially more of two of
      these proteins, factor VIIa and activated protein C, than did equivalent bilayers
      containing PS. Consistent with this finding, liposomes containing PA supported
      higher proteolytic activity by factor VIIa and activated protein C toward their
      natural substrates (factors X and Va, respectively) than did PS-containing
      liposomes. Moreover, treating activated human platelets with phospholipase D
      enhanced the rates of factor X activation by factor VIIa in the presence of
      soluble tissue factor. We hypothesize that factor VII and protein C bind
      preferentially to the monoester phosphate of PA because of its accessibility and
      higher negative charge compared with the diester phosphates of most other
      phospholipids. We further found that phosphatidylinositol 4-phosphate, which
      contains a monoester phosphate attached to its myo-inositol headgroup, also
      supported enhanced enzymatic activity of factor VIIa and activated protein C. We
      conclude that factor VII and protein C bind preferentially to monoester
      phosphates, which may have implications for the function of these proteases in
      vivo. 

PMID- 23879868
TI  - Psoriatic uveitis responding to adalimumab therapy.

PMID- 23879869
TI  - Accuracy of a digital impression system based on active wavefront sampling
      technology for implants considering operator experience, implant angulation, and
      depth.
AB  - BACKGROUND: There is a scarce knowledge on the accuracy of intraoral digital
      impression systems for dental implants. PURPOSE: The purpose of this study is to
      evaluate the accuracy of a digital impression system considering clinical
      parameters. MATERIALS AND METHODS: A master model with six implants (27, 25, 22,
      12, 15, 17) was fitted with polyether ether ketone scan bodies. Implant no. 25
      was placed with 30 degrees  mesial angulation in relation to the vertical plane
      (y axis), and implant no. 15 was positioned with 30 degrees  distal angulation.
      Implant no. 22 was placed 2 mm and no. 12, 4 mm below the gingiva. Experienced (n
      = 2) and inexperienced operators (n = 2) performed scanning (Lava Chairside Oral
      Scanner; 3 M ESPE, St Paul, MN, USA) at standard and high accuracy mode.
      Measurements involved five distances (27-25, 27-22, 27-12, 27-15, 27-17).
      Measurements with high accuracy three-dimensional coordinated measuring machine
      (CMM) of the master model acted as the true values. The data obtained were
      subtracted from those of the CMM values. RESULTS: Experience of the operator
      significantly influenced the results (p = .000). Angulation (p = .195) and depth
      of implant (p = .399) did not show significant deviation from the true values.
      The mean difference between standard and high accuracy mode was 90 MUm.
      CONCLUSIONS: With the active wavefront sampling, technology-based digital
      impression system training seems to be compulsory. Impressions of angulated
      implants may diminish the accuracy of the impression, yet the results were not
      significant.

PMID- 23879870
TI  - Examination of unmet treatment needs among persons with episodic migraine:
      results of the American Migraine Prevalence and Prevention (AMPP) Study.
AB  - BACKGROUND: Despite the expanding therapeutic armamentarium, many people with
      episodic migraine (EM) have unmet acute treatment needs. OBJECTIVE: To determine
      the relative frequency of prespecified types of "unmet treatment needs" in
      persons with EM in a US population-based sample. METHODS: Eligible participants
      completed the 2009 American Migraine Prevalence and Prevention Study survey and
      met International Classification of Headache Disorders-2nd edition (ICHD-2)
      criteria for migraine with an average headache day frequency of <15 days per
      month (EM). We identified 5 domains of unmet treatment needs: (1) dissatisfaction
      with current acute treatment using 3 summary items from the Patient Perception of
      Migraine Questionnaire-revised edition (PPMQ-R); (2) moderate or severe headache
      related disability defined by a Migraine Disability Assessment Scale score of
      >=11; (3) excessive use of opioids or barbiturates defined as use on >=4
      days/month or by meeting Diagnostic and Statistical Manual for Mental Disorders
      4th edition criteria for dependence; (4) recurrent use of the emergency
      department or urgent care clinic for headache defined by >=2 visits in the
      preceding year for headache; and (5) history of cardiovascular events indicating
      a possible contraindication to triptan use. For each respondent, we identified
      their unmet treatment needs in each category and classified them as having no
      unmet needs or 1 or more unmet needs. RESULTS: Of 5591 respondents with EM, 2274
      (40.7%) had 1 or more unmet needs; 1467 (26.2%) had exactly 1 unmet need, and 807
      (14.4%) had 2 or more unmet needs. Among those with at least 1 unmet need, 1069
      (47.0%) had moderate or severe headache-related disability, 851 (37.4%) were
      dissatisfied with their acute treatment regimen, 728 (32.0%) had excessive opioid
      or barbiturate use and/or probable dependence, 595 (26.2%) had a history of
      cardiovascular events, and 129 (5.7%) reported >=2 visits in the preceding year
      to the emergency department/urgent care clinic for headache. Persons with more
      headache days, depression, or generalized anxiety were more likely to have unmet
      treatment needs. CONCLUSION: In a population sample of individuals with EM, more
      than 40% have at least 1 unmet need in the area of acute treatment. The leading
      reasons for unmet needs, which include headache-related disability and
      dissatisfaction with current acute treatment, suggest opportunities for improving
      outcomes for persons with EM.

PMID- 23879871
TI  - The inhibitory effect of micafungin on biofilm formation by Pseudomonas
      aeruginosa.
AB  - This study assesses the potential effect of micafungin, an antifungal agent known
      to inhibit 1,3-beta-D-glucan synthesis in Candida albicans, on biofilm formation
      of selected Pseudomonas aeruginosa isolates by decreasing the synthesis of
      extracellular matrix beta-D-glucan forming units. The effect of an optimal
      therapeutic dose of 10 mg ml(-1) micafungin on the production of biofilm was
      monitored in vitro using a microtiter plate assay. Phenotypic reduction in the
      formation of biofilm was significant (based on average optical density; p < 0.05)
      in most of the isolates. Moreover, the relative gene expression of biofilm
      encoding genes for alginate and pellicles (algC and pelC, respectively), and the
      cell wall 1,3-beta-D-glucan encoding gene (ndvB) was evaluated using quantitative
      reverse transcription PCR. For all the genes tested, the levels of mRNA
      transcription were also decreased significantly (p < 0.05) in micafungin-treated
      samples cf. their untreated counterparts. In conclusion, this study presents
      micafungin as a potential agent for disrupting the structure of a biofilm of P.
      aeruginosa allowing the possible exposure and treatment of core-planktonic cells.

PMID- 23879872
TI  - Comparative analysis of Staphylococcus aureus and Escherichia coli
      microcalorimetric growth.
AB  - BACKGROUND: Microcalorimetric bacterial growth studies have illustrated that
      thermograms differ significantly with both culture media and strain. The present
      contribution examines the possibility of discriminating between certain bacterial
      strains by microcalorimetry and the qualitative and quantitative contribution of
      the sample volume to the observed thermograms. Growth patterns of samples of
      Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) were
      analyzed. Certain features of the thermograms that may serve to distinguish
      between these bacterial strains were identified. RESULTS: The thermograms of the
      two bacterial strains with sample volumes ranging from 0.3 to 0.7 ml and same
      initial bacterial concentration were analyzed. Both strains exhibit a roughly 2
      peak shape that differs by peak amplitude and position along the time scale.
      Seven parameters corresponding to the thermogram key points related to time and
      heat flow values were proposed and statistically analyzed. The most relevant
      parameters appear to be the time to reach a heat flow of 0.05 mW (1.67 +/- 0.46 h
      in E. coli vs. 2.99 +/- 0.53 h in S. aureus, p < 0.0001), the time to reach the
      first peak (3.84 +/- 0.5 h vs. 5.17 +/- 0.49 h, p < 0.0001) and the first peak
      value (0.19 +/- 0.02 mW vs. 0.086 +/- 0.012 mW, p < 0.0001). The statistical
      analysis on 4 parameters of volume-normalized heat flow thermograms showed that
      the time to reach a volume-normalized heat flow of 0.1 mW/ml (1.75 +/- 0.37 h in
      E. coli vs. 2.87 +/- 0.65 h in S. aureus, p < 0.005), the time to reach the first
      volume-normalized peak (3.78 +/- 0.47 h vs. 5.12 +/- 0.52 h, p < 0.0001) and the
      first volume-normalized peak value (0.35 +/- 0.05 mW/ml vs. 0.181 +/- 0.040
      mW/ml, p < 0.0001) seem to be the most relevant. Peakfit(r) decomposition and
      analysis of the observed thermograms complements the statistical analysis via
      quantitative arguments, indicating that: (1) the first peak pertains to a faster,
      "dissolved oxygen" bacterial growth (where the dissolved oxygen in the initial
      suspension acts as a limiting factor); (2) the second peak indicates a slower
      "diffused oxygen" growth that involves transport of oxygen contained in the
      unfilled part of the microcalorimetric cell; (3) a strictly fermentative growth
      component may slightly contribute to the observed complex thermal signal.
      CONCLUSION: The investigated strains of Staphylococcus aureus and Escherichia
      coli display, under similar experimental conditions, distinct thermal growth
      patterns. The two strains can be easily differentiated using a selection of the
      proposed parameters. The presented Peakfit analysis of the complex thermal signal
      provides the necessary means for establishing the optimal growth conditions of
      various bacterial strains. These conditions are needed for the standardization of
      the isothermal microcalorimetry method in view of its further use in qualitative
      and quantitative estimation of bacterial growth.

PMID- 23879874
TI  - Effect of phytic acid used as etchant on bond strength, smear layer, and pulpal
      cells.
AB  - This study aimed to evaluate the effect of phytic acid (IP6), used as etchant, on
      resin-dentin bond strength, smear layer removal, and the viability of pulpal
      cells. Flat dentin surfaces with smear layer were etched with 1% IP6 for 60, 30,
      or 15 s; in the control group 37% phosphoric acid (PA) was used. Dentin surfaces
      were rinsed, blot-dried, and bonded with an etch-and-rinse adhesive, followed by
      composite build-ups. The specimens were subjected to tensile testing after 24 h
      of water storage at 37 degrees C, and failure modes were determined using
      scanning electron microscopy. The effectiveness of IP6 to remove the smear layer
      was observed using scanning electron microscopy. To evaluate the effect on pulpal
      cells, solutions of 0.1 and 0.01% IP6 and of 3.7 and 0.37% PA were prepared and
      rat pulpal cells were treated with these solutions for 6 and 24 h. Cell viability
      was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. The results demonstrated that all application times of IP6
      produced bond-strength values that were significantly higher than that of the
      control. Phytic acid effectively removed the smear layer and plugs, thus exposing
      the collagen network. Phytic acid had a minimal effect on pulpal cells, whereas
      PA resulted in a marked decrease in their viability.

PMID- 23879873
TI  - Genetic variants predicting left ventricular hypertrophy in a diabetic
      population: a Go-DARTS study including meta-analysis.
AB  - BACKGROUND: Left ventricular hypertrophy has multiple aetiologies including
      diabetes and genetic factors. We aimed to identify genetic variants predicting
      left ventricular hypertrophy in diabetic individuals. METHODS: Demographic,
      echocardiographic, prescribing, morbidity, mortality and genotyping databases
      connected with the Genetics of Diabetes Audit and Research in Tayside, Scotland
      project were accurately linked using a patient-specific identifier. Left
      ventricular hypertrophy cases were identified using echocardiographic
      data.Genotyping data from 973 cases and 1443 non-left ventricular hypertrophy
      controls were analysed, investigating whether single nucleotide polymorphisms
      associated with left ventricular hypertrophy in previous Genome Wide Association
      Studies predicted left ventricular hypertrophy in our population of individuals
      with type 2 diabetes. Meta-analysis assessed overall significance of these single
      nucleotide polymorphisms, which were also used to create gene scores. Logistic
      regression assessed whether these scores predicted left ventricular hypertrophy.
      RESULTS: Two single nucleotide polymorphisms previously associated with left
      ventricular hypertrophy were significant: rs17132261: OR 2.03, 95% CI 1.10-3.73,
      p-value 0.02 and rs2292462: OR 0.82, 95% CI 0.73-0.93 and p-value 2.26x10-3. Meta
      analysis confirmed rs17132261 and rs2292462 were associated with left ventricular
      hypertrophy (p=1.03x10-8 and p=5.86x10-10 respectively) and one single nucleotide
      polymorphisms in IGF1R (rs4966014) became genome wide significant upon meta
      analysis although was not significant in our study. Gene scoring based on
      published single nucleotide polymorphisms also predicted left ventricular
      hypertrophy in our study.Rs17132261, within SLC25A46, encodes a mitochondrial
      phosphate transporter, implying abnormal myocardial energetics contribute to left
      ventricular hypertrophy development. Rs2292462 lies within the obesity-implicated
      neuromedin B gene. Rs4966014 lies within the IGF1R1 gene. IGF1 signalling is an
      established factor in cardiac hypertrophy. CONCLUSIONS: We created a resource to
      study genetics of left ventricular hypertrophy in diabetes and validated our left
      ventricular hypertrophy phenotype in replicating single nucleotide polymorphisms
      identified by previous genome wide association studies investigating left
      ventricular hypertrophy.

PMID- 23879875
TI  - Predictors of substance use reduction in an epidemiological first-episode
      psychosis cohort.
AB  - AIM: To assess the predictors of a significant decrease or cessation of substance
      use (SU) in a treated epidemiological cohort of first-episode psychosis (FEP)
      patients. METHOD: Participants were FEP patients of the Early Psychosis
      Prevention and Intervention Centre in Australia. Patients' medical files were
      reviewed using a standardized file audit. Data on 432 patients with FEP and
      baseline co-morbid substance use disorder (SUD) were available for analysis.
      Predictors of reduction/cessation of SU at follow up were examined using logistic
      regression analyses. RESULTS: In univariate analyses, a reduction/cessation of SU
      was predicted by baseline measures reflecting higher education, employment,
      accommodation with others, cannabis use disorder (CUD) only (rather than poly
      SUDs), better global functioning and better premorbid social and occupational
      functioning, later age at onset of psychosis, and a diagnosis of non-affective
      psychosis. In multivariate analysis, CUD alone and better premorbid social and
      occupational functioning remained significant predictors. CONCLUSIONS: Addressing
      SUDs and social and occupational goals in people with FEP may offer opportunities
      to prevent SUDs becoming more severe or entrenched. Further longitudinal research
      on recovery from SU and FEP is needed to disentangle directions of influence and
      identify key targets for intervention.

PMID- 23879876
TI  - Evaluation of inter-observer variability of bladder boundary delineation on cone
      beam CT.
AB  - BACKGROUND: In-room cone-beam computerized tomography (CBCT) imaging is a
      promising method to reduce setup errors, especially in organs such as the bladder
      that often have large intrafractional variations due to organ movement. CBCT
      image quality is limited by low contrast and imaging artifacts, but few data have
      been reported about inter-observer variability of bladder boundary delineation on
      CBCT. The aim of this work was to analyze and evaluate the inter-observer
      contouring uncertainties of bladder boundary delineation on CBCT images in a
      prospective fashion. METHODS: Five radiation oncologists contoured 10 bladders
      using the CBCT datasets of consecutive 10 patients (including 4 females) who were
      irradiated to the pelvic region. Prostates were also contoured in male patients.
      Patients who had had prostatectomy were excluded. The coefficient of variation
      (COV), conformity index (CI(gen)), and coordinates of center-of-mass (COM) of the
      bladder and prostate were calculated for each patient. RESULTS: The mean COV for
      the bladder and prostate was 0.08 and 0.20, respectively. The mean CI(gen) of the
      bladder and prostate was 0.81 and 0.66, respectively. The root mean square (RMS)
      of the inter-observer standard deviation (sigma) of the COM displacement in the
      left-right (LR) and anterior-posterior (AP) direction was 0.79, 0.87 and 0.54 for
      the bladder and 0.63, 0.99 and 1.72 for the prostate. Regarding the mean COV and
      CI(gen) for the bladder, the differences between males and females were not
      significant. CONCLUSIONS: Inter-observer variability for bladder delineation on
      CBCT images was substantially small regardless of gender. We believe that our
      results support the applicability of CBCT in adaptive radiotherapy for bladder
      cancer.

PMID- 23879877
TI  - Look again: effects of brain images and mind-brain dualism on lay evaluations of
      research.
AB  - Brain scans have frequently been credited with uniquely seductive and persuasive
      qualities, leading to claims that fMRI research receives a disproportionate share
      of public attention and funding. It has been suggested that functional brain
      images are fascinating because they contradict dualist beliefs regarding the
      relationship between the body and the mind. Although previous research has
      indicated that brain images can increase judgments of an article's scientific
      reasoning, the hypotheses that brain scans make research appear more interesting,
      surprising, or worthy of funding have not been tested. Neither has the relation
      between the allure of brain imaging and dualism. In the following three studies,
      laypersons rated both fictional research descriptions and real science news
      articles accompanied by brain scans, bar charts, or photographs. Across 988
      participants, we found little evidence of neuroimaging's seductive allure or of
      its relation to self-professed dualistic beliefs. These results, taken together
      with other recent null findings, suggest that brain images are less powerful than
      has been argued. 

PMID- 23879878
TI  - Suture anchor placement technique around the insertion of the ventral rectus
      muscle for the replacement of the prolapsed gland of the third eyelid in dogs:
      100 dogs.
AB  - OBJECTIVE: To evaluate a rapid and efficacious procedure to anchor the prolapsed
      gland of the third eyelid in dogs. METHODS: This is a retrospective study of 100
      affected dogs (122 eyes) with third eyelid gland prolapse that were surgically
      anchored with a nonabsorbable suture around the insertion of the ventral rectus
      muscle. RESULTS: Hundred dogs (122 eyes) were included in this study. Twenty
      three pure-bred and several mixed-breed dogs were represented with the right eye
      affected in 60 cases and the left eye in 62 cases. Thirty-four eyes (27.9%) were
      previously operated on at another facility prior to referral. The average age of
      the patients was 2.2 years (57 days to 11 years). No recurrences of gland
      prolapse were observed over the course of study. Minor intraoperative
      conjunctival perforations were observed and easily repaired at the time of the
      surgery in 21 cases (17.2%). Five cases demonstrated preexistent
      keratoconjunctivitis sicca (KCS), and all had improved Schirmer tear test
      following surgical correction and medical therapy. CONCLUSIONS: The suture anchor
      placement technique provides a cosmetic, rapid, and successful replacement of the
      prolapsed gland of the third eyelid in dogs. No recurrences were noted.
      Complications were easily addressed.

PMID- 23879879
TI  - Egg parasitoids of the corn leafhopper, Dalbulus maidis, in the southernmost area
      of its distribution range.
AB  - Egg parasitoids of the corn leafhopper, Dalbulus maidis (DeLong and Wolcott)
      (Hemiptera: Cicadellidae), were surveyed exposing sentinel eggs of the leafhopper
      along a latitudinal transect of 600 km in Argentina, the southernmost area of its
      distribution range. Four parasitoid species were obtained: the mymarids Anagrus
      breviphragma Soyka (Hymenoptera: Mymaridae), Anagrus flaveolus Waterhouse, and
      Polynema sp., and the trichogrammatid Pseudoligosita longifrangiata (Viggiani)
      (Hymenoptera: Trichogrammatidae). The low parasitism rate, low species richness,
      and high proportion of generalist egg parasitoids were quite clear in the
      southern distribution limit of the vector, in contrast to regions where corn
      crops are available all year round and there are continuous and overlapping
      generations of the pest. Further studies need to be done in order to determine
      the native host of the above egg parasitoids, the seasonal abundance, and the
      possible occurrence of other species affecting D. maidis populations in the
      studied area.

PMID- 23879880
TI  - Disentangling electronic and vibronic coherences in two-dimensional echo spectra.
AB  - The prevalence of long-lasting oscillatory signals in two-dimensional (2D) echo
      spectroscopy of light-harvesting complexes has led to a search for possible
      mechanisms. We investigate how two causes of oscillatory signals are intertwined:
      (i) electronic coherences supporting delocalized wavelike motion and (ii) narrow
      bands in the vibronic spectral density. To disentangle the vibronic and
      electronic contributions, we introduce a time-windowed Fourier transform of the
      signal amplitude. We find that 2D spectra can be dominated by excitations of
      pathways which are absent in excitonic energy transport. This leads to an
      underestimation of the lifetime of electronic coherences by 2D spectra. 

PMID- 23879881
TI  - A hybrid method based on level set and 3D region growing for segmentation of the
      thoracic aorta.
AB  - This study sought to develop a completely automatic method for image segmentation
      of the thoracic aorta. We used a total of 4682 images from 10 consecutive
      patients. The proposed method is based on the use of level set and region
      growing, automatically initialized using the Hough transform. The results
      obtained were compared to those of manual segmentation as performed by an
      external expert radiologist. Concordance between the developed method and manual
      segmentation ranged from 92.79 to 95.77% in the descending regions of the aorta
      and from 90.68 to 96.54% in the ascending regions, with a mean value of 93.83%
      being obtained for total segmentation.

PMID- 23879882
TI  - Zingiberenol, (1R,4R,1'S)-4-(1',5'-Dimethylhex-4'-enyl)-1-methylcyclohex-2-en-1
      ol, identified as the sex pheromone produced by males of the rice stink bug
      Oebalus poecilus (heteroptera: pentatomidae).
AB  - Bioassays using an olfactometer showed that Oebalus poecilus males produce the
      sexual pheromone, and the chemical analysis demonstrated that this compound is
      zingiberenol. Two groups of isomers, each containing four diastereoisomers,
      (1RS,4RS,1'S)- and (1RS,4RS,1'R)-zingiberenol, were prepared. These
      diastereoisomers were not separated on a chiral GC column. Therefore, to
      determine the absolute configuration of the carbon 1, 4, and 1' of zingiberenol
      produced by males, the following strategies were conducted. The extract
      containing males volatiles was submitted to dehydration microchemistry to produce
      zingiberene, in which the isomers are separated by chiral GC analysis, and by
      comparison with the natural zingiberene from ginger oil, the absolute
      stereochemistry of the carbons 4 and 1' was determined to be R and S,
      respectively, and the carbon 1 was determined as R from the (13)C NMR spectra of
      quercivorol. Finally, the bioassays showed that O. poecilus females responded to
      racemic mixture and to (1RS,4RS,1'S)-zingiberenol.

PMID- 23879883
TI  - Enzymatic assay for Cu(II) with horseradish peroxidase and its application in
      colorimetric logic gate.
AB  - We report an ultrasensitive and colorimetric assay for Cu(II) via enzymatic
      amplification strategy. The enzymatic activity of horseradish peroxidase (HRP) is
      strongly inhibited by Cu(I), which can be used indirectly to assay Cu(II). The
      limit of detection (LOD) is 0.37 nM, and the detection of 20 nM Cu(II) in
      solution can be achieved with naked eyes. This assay can be used to construct a
      colorimetric logic gate. 

PMID- 23879884
TI  - Objective and subjective assessments of lighting in a hospital setting:
      implications for health, safety and performance.
AB  - A field study was conducted to evaluate the illumination levels, to examine the
      effect of lighting conditions (including lighting characteristics and
      disturbances) on employee satisfaction, job performance, safety and health, and
      to compare the employees' perception of lighting level with actual illuminance
      levels in a hospital setting using both questionnaire and physical illuminance
      measurements. The illumination levels varied across different locations within
      the hospital and were lower than standards for 52.2% of the workplaces surveyed.
      Most respondents indicated that at least one of the four lighting characteristics
      (i.e. light level, type of light sources, light colour and use of daylight) was
      inappropriate, and that at least one of the three lighting disturbances (i.e.
      flickering lights, glare and unwanted shadows) was a major disturbance to them.
      The employees' perceptions of illuminance generally reflected the actual
      illuminance levels. The more appropriate maintenance or installation of lighting
      fixtures was rated as the most appropriate for improving lighting. The findings
      suggest that environmental ergonomics should be given a more prominent role in
      hospital building and workplace design to support safer healthcare facilities
      (for staff and potentially for patients). PRACTITIONER SUMMARY: Good lighting is
      essential to improve employee performance, health and safety. The findings
      suggest that quantitative physical measurements should be supplemented by
      qualitative subjective assessments to provide a more holistic approach where
      specific details about the lighting condition in each working environment are
      incorporated from the workers' perspective.

PMID- 23879885
TI  - Interactions of the amphiphiles arbutin and tryptophan with phosphatidylcholine
      and phosphatidylethanolamine bilayers in the dry state.
AB  - BACKGROUND: Water is essential for life, but some organisms can survive complete
      desiccation, while many more survive partial dehydration during drying or
      freezing. The function of some protective molecules, such as sugars, has been
      extensively studied, but much less is known about the effects of amphiphiles such
      as flavonoids and other aromatic compounds. Amphiphiles may be largely soluble
      under fully hydrated conditions, but will partition into membranes upon removal
      of water. Little is known about the effects of amphiphiles on membrane stability
      and how amphiphile structure and function are related. Here, we have used two of
      the most intensively studied amphiphiles, tryptophan (Trp) and arbutin (Arb),
      along with their isolated hydrophilic moieties glycine (Gly) and glucose (Glc) to
      better understand structure-function relationships in amphiphile-membrane
      interactions in the dry state. RESULTS: Fourier-transform infrared (FTIR)
      spectroscopy was used to measure gel-to-liquid crystalline phase transition
      temperatures (Tm) of liposomes formed from phosphatidylcholine and
      phosphatidylethanolamine in the presence of the different additives. In anhydrous
      samples, both Glc and Arb strongly depressed Tm, independent of lipid
      composition, while Gly had no measurable effect. Trp, on the other hand, either
      depressed or increased Tm, depending on lipid composition. We found no evidence
      for strong interactions of any of the compounds with the lipid carbonyl or
      choline groups, while all additives except Gly seemed to interact with the
      phosphate groups. In the case of Arb and Glc, this also had a strong effect on
      the sugar OH vibrations in the FTIR spectra. In addition, vibrations from the
      hydrophobic indole and phenol moieties of Trp and Arb, respectively, provided
      evidence for interactions with the lipid bilayers. CONCLUSIONS: The two
      amphiphiles Arb and Trp interact differently with dry bilayers. The interactions
      of Arb are dominated by contributions of the Glc moiety, while the indole governs
      the effects of Trp. In addition, only Trp-membrane interactions showed a strong
      influence of lipid composition. Further investigations, using the large
      structural diversity of plant amphiphiles will help to understand how their
      structure determines the interaction with membranes and how that influences their
      biological functions, for example under freezing or dehydration conditions.

PMID- 23879886
TI  - Multidrug-resistant bacterial isolates in infected wounds at Jimma University
      Specialized Hospital, Ethiopia.
AB  - BACKGROUND: The term 'Multidrug-resistant' (MDR) applies to a bacterium that is
      simultaneously resistant to a number of antimicrobials belonging to different
      chemical classes. The effectiveness of currently available antmicrobial drugs is
      decreasing due to the increasing number of resistant strains causing infections
      so that available therapeutic options for such organisms are severely limited.
      OBJECTIVE: The aim of this study was to determine multidrug-resistance rate of
      bacterial isolates that caused wound infections. METHODS: A Hospital based cross
      sectional study was conducted on 322 wound samples taken from consecutive
      patients seen at inpatient and outpatient department of Jimma University
      Specialized Hospital from June to December 2011. Swabs from surgical incisions,
      burns, abscess and traumatic wounds were collected aseptically using Levine's
      technique. Bacteriological culture and examination was done following standard
      microbiological techniques. Multidrug-resistance test was performed by disk
      diffusion method against 10 classes of antimicrobials. The data was analyzed for
      descriptive statistics using SPSS version 16 and Microsoft Excel. RESULTS: The
      overall MDR among gram positive and gram negative bacterial isolates were (77%)
      and (59.3%) respectively. About, 86.2% S.aureus and 28.6% of Coagulase negative
      Staphylococci became MDR. Nearly 30.1% of S.aureus was resistant to six classes
      of antimicrobials. The average MDR rate of Proteus, Klebsiella, and Providencia
      species was 74.8%, 69.6% and 75% in that order. Nearly, 30.8% of Proteus sp,
      32.6% of Klebsiella sp and 61% of Citrobacter sp were resistance to 4 classes
      each. Surprisingly, the average MDR rate for Citrobacter sp was 100%. About
      (76.7%) of S.aureus was Oxacillin/Methicillin resistant while (16.4%) were
      Vancomycin resistant. Proteus species was the predominant isolates (27.9%)
      followed by P.aeruginosa and S.aureus (19.3%) and (19%) respectively. CONCLUSION:
      This study indicated that, the overall rate of MDR bacterial pathogens that
      caused wound infection was very high and many of the isolates were also
      identified as resistant to three or more classes of antimicrobials. Such
      widespread resistance to antimicrobial classes is something serious because a few
      treatment options remain for patients with wound infections. Periodic monitoring
      of etiology and antimicrobial susceptibility in areas where there is no culture
      facility is essential to assists physician in selection of chemotherapy.

PMID- 23879887
TI  - Monitoring avian influenza A(H7N9) virus through national influenza-like illness
      surveillance, China.
AB  - In China during March 4-April 28, 2013, avian influenza A(H7N9) virus testing was
      performed on 20,739 specimens from patients with influenza-like illness in 10
      provinces with confirmed human cases: 6 (0.03%) were positive, and increased
      numbers of unsubtypeable influenza-positive specimens were not seen. Careful
      monitoring and rapid characterization of influenza A(H7N9) and other influenza
      viruses remain critical. 

PMID- 23879889
TI  - The benefit of whole brain reirradiation in patients with multiple brain
      metastases.
AB  - BACKGROUND: To assess the outcomes, symptom palliation and survival rates in
      patients who received repeat whole brain radiotherapy (WBRT). METHODS: Twenty
      eight patients who had progression of brain metastasis received a second course
      of WBRT. Univariate log-rank testing and multivariate Cox regression analysis
      were used to determine the factors for death among several variables (cumulative
      BED [BEDcumulative], primary tumor site, Karnofsky performance scale [KPS],
      previous SRS, number of metastases and absence of extracranial metastases).
      Correlations between variables and treatment response were evaluated with the Chi
      squared test. RESULTS: The median KPS was 60 (range 50 to 100) at the initiation
      of reirradiation. The median time interval between the two courses of WBRT was
      9.5 months (range 3-27 months). The median doses of the first course and the
      second course of WBRT were 30 Gy (range 20 to 30 Gy) and 25 Gy (range 20 to 30
      Gy), respectively. The mean BEDcumulative was 129.5 Gy (range 110 to 150 Gy).
      Severe or unexpected toxicity was not observed. Symptomatic response was detected
      in 39% of the patients. The median overall survival following reirradiation was 3
      months (range 1 to 12 months, 95% CI 1.82-4.118). Survival was significantly
      better in responders (median 10 months, 95% CI 3.56-16.43) compared with non
      responders (median 2 months, 95% CI 1.3-2.64) (p = 0.000). In multivariate
      analysis, patients that had lung cancer (p = 0.01), initial KPS >=60 (p = 0.03)
      or longer intervals to reirradiation (p = 0.01) had significantly better survival
      rates. CONCLUSIONS: A careful second course of whole brain irradiation might
      provide a symptomatic and survival benefit in patients with good performance
      status and longer cranial progression-free intervals.

PMID- 23879888
TI  - Homologous lactoferrin triggers mobilization of the myelocytic lineage of bone
      marrow in experimental mice.
AB  - The effects of lactoferrin (LF), an iron binding protein, on myelopoiesis have
      been studied extensively in vitro and in vivo in human and murine models over the
      past three decades. Due to the lack of high-quality homologous LFs, however, the
      conclusions are still unequivocal. Recently, both human and murine LFs have
      become available as recombinant products expressed in Chinese hamster ovary (CHO)
      cell lines showing mammalian type of glycosylation, thus apparently species
      compatible. In this study, we present the effects of homologous recombinant mouse
      LF (rmLF) on myelopoiesis in CBA mice. The myelocytic lineage has been assessed
      by their appearance in circulating blood and bone marrow, and induction of
      relevant mediators of inflammation. Intravenous injection of rmLF (100 MUg/mouse)
      resulted in a significantly increased number of myelocytic cells in the
      circulating blood after 24 h. Mouse serum transferrin, used as a control protein,
      showed no stimulatory effect. The increase in output of neutrophil precursors,
      neutrophils, and eosinophils was correlated with a twofold increase of leukocyte
      concentrations. The analysis of the bone marrow sections confirmed increased
      myelopoiesis. The alterations in the bone marrow cell composition were
      statistically significant regarding mature neutrophils (10.8% vs. 27.7%),
      metamyelocytes (11.4% vs. 16.0%), and myelocytes (2.4% vs. 4.0%). The
      mobilization of the myelocytic cells in the bone marrow and the increased output
      of these cells into circulation were accompanied by elevated serum concentrations
      of interleukin-6 at 6 h and haptoglobin at 24 h following administration of rmLF.
      In conclusion, the homologous LF elicits significant and transient myelopoiesis
      in experimental mice.

PMID- 23879890
TI  - Effects of dipeptidyl peptidase-4 inhibitors in a type 2 diabetes patient with
      failure of glucagon-like peptide-1 receptor agonists.

PMID- 23879891
TI  - Nature of quantum states created by one photon absorption: pulsed coherent vs
      pulsed incoherent light.
AB  - We analyze electronically excited nuclear wave functions and their coherence when
      subjecting a molecule to the action of natural, pulsed incoherent solar-like
      light and to that of ultrashort coherent light assumed to have the same center
      frequencies and spectral bandwidths. Specifically, we compute the spatiotemporal
      dependence of the excited wave packets and their electronic coherence for these
      two types of light sources, on different electronic potential energy surfaces.
      The resultant excited state wave functions are shown to be dramatically
      different, reflecting the light source from which they originated. In addition,
      electronic coherence is found to decay significantly faster for incoherent light
      than for coherent ultrafast excitation, for both continuum and bound wave
      packets. These results confirm that the dynamics observed from ultrashort
      coherent excitation does not reflect what happens in processes induced by solar
      like radiation, and conclusions drawn from one do not, in general, apply to the
      other. These results provide further support to the view that the dynamics
      observed in studies using ultrashort coherent pulses can be significantly
      different than those that would result from excitation with natural incoherent
      light. 

PMID- 23879892
TI  - Influence on the behavior of lung cancer H1299 cells by silencing SLC35F2
      expression.
AB  - BACKGROUND: To investigate the effects of RNA interference-mediated
      downregulation of Human Solute Carrier Family 35 member F2 (SLC35F2) expression
      on the biological behavior of lung cancer H1299 cells. METHODS: The lentiviral
      vector of small interfering RNA targeting SLC35F2 was introduced into H1299 cells
      by liposome-mediated transfection. Expression of the SLC35F2 protein was measured
      by western blot. The proliferation of H1299 cells was determined by Cell Counting
      Kit-8 assay. The migration of H1299 cells was measured by Transwell migration
      assay. Cell cycle analysis used fluorescence-activated cell sorting. RESULTS:
      SLC35F2 expression was markedly downregulated in H1299 cell clone (transfected
      with the lentiviral vector harboring small interfering RNA targeting SLC35F2).
      Proliferation decreased significantly compared with that of non-transfected H1299
      cells. Transwell migration assay showed that fewer cells moved through the
      artificial basement membrane compared with untransfected H1299 cells (38.3 +/-
      5.7 vs. 113.5 +/- 8.5, P < 0.05). The cell cycle of H1299 cells was changed, the
      percentage of H1299 cells in S and G2/M phases being significantly decreased
      compared with untransfected H1299 cells (S phase: 15.3% +/- 3.0% vs. 27.0% +/-
      5.4%, P > 0.05; G2/M phase; 3.0% +/- 1.1% vs. 10.5% +/- 1.7%, P < 0.05), whereas
      the percentage of H1299 cells in G0/G1 phase increased markedly (81.7% +/- 4.0%
      vs. 62.5% +/- 1.9%, P < 0.05). CONCLUSION: RNA interference-mediated
      downregulation of SLC35F2 expression by lentiviral vector can attenuate the
      proliferation, migration and invasion of H1299 cells.

PMID- 23879893
TI  - Twenty-four hours abstinence and the quality of sperm parameters.
AB  - Patients with abnormal basic parameters and mainly low concentration can be
      expected to have improved parameters on the second consecutive day. As the number
      of abnormal basic parameters increases, the more significant improvement can be
      expected. On the other hand, patients with normal or few abnormal basic semen
      parameters show a decrease after 24 h. Furthermore, the magnitude of change to
      both directions in TMC and TNMC values in these patients emphasises these
      conclusions. Based on the type and mainly the combined number of abnormal basic
      semen parameters, insemination strategy can be tailored to male fertility
      patients. Those with abnormal concentration or multiple abnormal semen parameters
      may benefit from 2 consecutive day intercourses or inseminations or a short
      period of abstinence due to a significant improvement in the semen parameters on
      second day insemination. In those with normal basic semen parameters, a reduction
      in semen quality is expected after 24 h, and a single-timed insemination and
      longer abstinence can be recommended.

PMID- 23879894
TI  - Findings from the analysis of the American College of Nurse-Midwives' membership
      surveys: 2009 to 2011.
AB  - INTRODUCTION: The American College of Nurse-Midwives (ACNM) Core Data Survey is
      an annual membership survey that collects demographic and selected workforce data
      about certified nurse-midwives (CNMs), certified midwives (CMs), and students
      enrolled in midwifery education programs accredited by the Accreditation
      Commission for Midwifery Education. These data are aggregated and published every
      3 years. This article presents findings from the analysis of membership data for
      the years 2009 to 2011. METHODS: An online survey is sent annually to all ACNM
      members who provide ACNM with an e-mail address. The survey instrument for 2009
      to 2011 focused on 5 categories: demographics, certification, education,
      employment, and licensure except for 2011, in which licensure data were collected
      separately. RESULTS: ACNM members responding to the surveys during 2009, 2010,
      and 2011 continued to remain predominantly white and female. The average age of
      CNMs/CMs in 2011 was 51.2 years. The majority had a master's degree as their
      highest degree, and 9.3% had a doctoral degree. Approximately two-thirds of
      respondents in each of the 3 survey years identified attendance at births as one
      of their primary responsibilities. DISCUSSION: Very little change in diversity
      was observed over the 3 survey years. The number of CNMs earning the doctor of
      nursing practice degree is increasing, whereas other doctoral degree categories
      remain stable. The majority of CNMs/CMs continue to identify a broad domain of
      clinical midwifery practice as their primary responsibility in their employment.
      The majority of respondents attend births, but the proportion has been decreasing
      slightly over time. Salaries for midwives continue to rise, but the reasons for
      this are unclear.

PMID- 23879895
TI  - Risk factors for sporadic infection with Salmonella Infantis: a matched case
      control study.
AB  - This matched case-control study investigated the risk factors for sporadic
      Salmonella Infantis infection in 263 affected children and 263 age-, gender- and
      neighbourhood-matched controls. Information about exposure to potential risk
      factors was obtained via telephone interview and evaluated by conditional
      logistic regression analysis. Age groups <= 1 year (n=77) and >1 year (n = 186)
      were analysed separately. Of those aged <= 1 year, breastfeeding was a
      significant protective factor against infection [matched odds ratio (mOR) 0.24,
      95% confidence interval (CI) 0.10-0.59, P < 0.01]. In the older group,
      consumption of eggs (mOR 1.87, 95% CI 1.00-3.49, P = 0.05) was a significant risk
      factor and thawing chicken in water (mOR 2.55, 95% CI 0.94-6.91, P = 0.07) was
      borderline risk factor, while consumption of carrots (mOR 0.46, 95% CI 0.26-0.83,
      P < 0.01), drinking tap water (mOR 0.44, 95% CI 0.22-0.85, P = 0.02), religious
      lifestyle (mOR 0.40, 95% CI 0.21-0.74, P < 0.01) and having a high number of
      children in the household (mOR 0.72, 95% CI 0.58-0.88, P < 0.01) were significant
      protective factors. Consumers should avoid eating undercooked eggs and food
      handlers should be educated regarding proper handling and cooking of eggs.
      Breastfeeding should be strongly encouraged by public health authorities. The
      public must be educated on stringent hygiene practices, especially proper cooking
      of eggs to reduce infection rates.

PMID- 23879896
TI  - Ultra-fast speech comprehension in blind subjects engages primary visual cortex,
      fusiform gyrus, and pulvinar - a functional magnetic resonance imaging (fMRI)
      study.
AB  - BACKGROUND: Individuals suffering from vision loss of a peripheral origin may
      learn to understand spoken language at a rate of up to about 22 syllables (syl)
      per second - exceeding by far the maximum performance level of normal-sighted
      listeners (ca. 8 syl/s). To further elucidate the brain mechanisms underlying
      this extraordinary skill, functional magnetic resonance imaging (fMRI) was
      performed in blind subjects of varying ultra-fast speech comprehension
      capabilities and sighted individuals while listening to sentence utterances of a
      moderately fast (8 syl/s) or ultra-fast (16 syl/s) syllabic rate. RESULTS:
      Besides left inferior frontal gyrus (IFG), bilateral posterior superior temporal
      sulcus (pSTS) and left supplementary motor area (SMA), blind people highly
      proficient in ultra-fast speech perception showed significant hemodynamic
      activation of right-hemispheric primary visual cortex (V1), contralateral
      fusiform gyrus (FG), and bilateral pulvinar (Pv). CONCLUSIONS: Presumably, FG
      supports the left-hemispheric perisylvian "language network", i.e., IFG and
      superior temporal lobe, during the (segmental) sequencing of verbal utterances
      whereas the collaboration of bilateral pulvinar, right auditory cortex, and
      ipsilateral V1 implements a signal-driven timing mechanism related to syllabic
      (suprasegmental) modulation of the speech signal. These data structures, conveyed
      via left SMA to the perisylvian "language zones", might facilitate - under time
      critical conditions - the consolidation of linguistic information at the level of
      verbal working memory.

PMID- 23879897
TI  - Survival and differentiation of adenovirus-generated induced pluripotent stem
      cells transplanted into the rat striatum.
AB  - Induced pluripotent stem cells (iPSCs) offer certain advantages over embryonic
      stem cells in cell replacement therapy for a variety of neurological disorders.
      However, reliable procedures, whereby transplanted iPSCs can survive and
      differentiate into functional neurons, without forming tumors, have yet to be
      devised. Currently, retroviral or lentiviral reprogramming methods are often used
      to reprogram somatic cells. Although the use of these viruses has proven to be
      effective, formation of tumors often results following in vivo transplantation,
      possibly due to the integration of the reprogramming genes. The goal of the
      current study was to develop a new approach, using an adenovirus for
      reprogramming cells, characterize the iPSCs in vitro, and test their safety,
      survivability, and ability to differentiate into region-appropriate neurons
      following transplantation into the rat brain. To this end, iPSCs were derived
      from bone marrow-derived mesenchymal stem cells and tail-tip fibroblasts using a
      single cassette lentivirus or a combination of adenoviruses. The reprogramming
      efficiency and levels of pluripotency were compared using immunocytochemistry,
      flow cytometry, and real-time polymerase chain reaction. Our data indicate that
      adenovirus-generated iPSCs from tail-tip fibroblasts are as efficient as the
      method we used for lentiviral reprogramming. All generated iPSCs were also
      capable of differentiating into neuronal-like cells in vitro. To test the in vivo
      survivability and the ability to differentiate into region-specific neurons in
      the absence of tumor formation, 400,000 of the iPSCs derived from tail-tip
      fibroblasts that were transfected with the adenovirus pair were transplanted into
      the striatum of adult, immune-competent rats. We observed that these iPSCs
      produced region-specific neuronal phenotypes, in the absence of tumor formation,
      at 90 days posttransplantation. These results suggest that adenovirus-generated
      iPSCs may provide a safe and viable means for neuronal replacement therapies. 

PMID- 23879898
TI  - Insecticide susceptibility of field-collected populations of Culex
      tritaeniorhynchus in the Republic of Korea.
AB  - The toxicities of 10 insecticides were examined against late third instar Culex
      tritaeniorhynchus Giles (Diptera: Culicidae) using the direct-contact mortality
      bioassay. Six geospatially-distant field mosquitoes were collected from Chuncheon
      si, Hwaseong, Seosan. Jeonju, Daegu, and Busan in the Republic of Korea. Marked
      regional variations of insecticide susceptibility were observed. Field
      populations of Seosan, Jeonju, and Daegu from agricultural areas showed higher to
      extremely higher insecticide susceptibility to pyrethroids than those of
      Chuncheon-si, Hwaseong, and Busan strains from non-agricultural areas. Extremely
      high to low levels of susceptibility were measured: bifenthrin, susceptible ratio
      (SR) = 2.7-896.3; beta-cyfluthrin, SR = 1.8-633.3; alpha-cypermethrin, SR = 1.2
      1,051.9; deltamethrin, SR = 1.3-711.1; permethrin, SR = 1.5-1,053.4; etofenprox,
      SR = 2.2-29.3; chlorfenapyr, SR = 5.1-103.6; chlorpyrifos, SR = 2.3- 337.0;
      fenitrothion, SR = 2.0-142.3; and fenthion, SR = 1.4-186.2. Cx. tritaeniorhynchus
      populations from rice paddies had been under heavy selection pressure due to the
      agricultural insecticides, and that's why the mosquito species demonstrated high
      resistance to pyrethroids, which were used for a long time to control
      agricultural pests in the localities. These results indicate that careful
      selection and rotational use of these insecticides may result in continued
      satisfactory control against field populations of Japanese encephalitis vector
      mosquitoes.

PMID- 23879899
TI  - Is chronic prostatic inflammation a new target in the medical therapy of lower
      urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH)?

PMID- 23879900
TI  - Are we ready for the new wave of focal therapy interventions for men with early
      prostate cancer?

PMID- 23879901
TI  - Impact of renal function on eligibility for chemotherapy and survival in patients
      who have undergone radical nephro-ureterectomy.

PMID- 23879902
TI  - A stitch in time saves nine: better training may avoid complications in robot
      assisted radical prostatectomy.

PMID- 23879903
TI  - Phase II study of everolimus in metastatic urothelial cancer.

PMID- 23879904
TI  - A real-life snapshot of the current trends of urinary diversion.

PMID- 23879905
TI  - If something looks too good to be true, it probably is.

PMID- 23879906
TI  - Lower limb compartment syndrome as a complication of robot-assisted radical
      prostatectomy: the UK experience.
AB  - OBJECTIVE: To evaluate the incidence of lower limb compartment syndrome (LLCS) in
      robot-assisted radical prostatectomy (RARP) and the prevalence of risk factors in
      patients with LLCS. METHODS: Data were collected from 17 UK robotic surgery
      institutions for a multicentre analysis. Data were used to calculate the
      incidence of LLCS and the prevalence of risk factors. RESULTS: A total of 3110
      RARPs were performed by 17 institutions between 2004 and 2011. There were nine
      cases of LLCS, giving an incidence of 0.29%. Seven of these required fasciotomy.
      The prevalence of risk factors was as follows: console time >4 h in 8/9 cases,
      early learning curve (<20 cases) in 3/9 cases; obesity (BMI >30 kg/m(2) ) in 5/9
      cases; and peripheral vascular disease in 2/9 cases. One patient with LLCS was
      positioned incorrectly. CONCLUSIONS: The serious complication LLCS occurs in RARP
      but has a low incidence. Long operating times, surgical inexperience, poor
      patient positioning, obesity and vascular disease appear to be risk factors.

PMID- 23879907
TI  - Bilateral focal ablation of prostate tissue using low-energy direct current
      (LEDC): a preclinical canine study.
AB  - OBJECTIVE: To evaluate side-effects, erectile function and capability to preserve
      adjacent tissues of bilateral focal prostate ablation using low-energy direct
      current (LEDC) in a canine model. MATERIALS AND METHODS: In all, 12 male Beagle
      dogs underwent bilateral focal prostate ablation using the NanoKnifeTM LEDC
      system. Three 19 G monopolar electrodes were transperineally placed on each side
      of the prostate under transrectal ultrasonographic (TRUS) guidance using a
      triangular probe array. Intra- and postoperative side-effects were recorded.
      Erectile function was evaluated at baseline and 4-5 and 26-27 days after
      ablation. The dogs were killed humanely at 7 (six) and 30 days (six) for gross
      and microscopic evaluation of the prostate and adjacent organs. RESULTS: The
      median (range) prostate volume on TRUS was 12.1 (8.9-17.2) mL. The electrodes
      were placed at a median distance of 0.55-0.66 cm from the capsule, urethra and
      rectum. All procedures were completed successfully and recovery was uneventful.
      There were no episodes of urinary retention. All the dogs were able to achieve
      erections after ablation. Pathological analyses revealed inflammatory changes in
      the ablation zone at 7 days and replacement by fibrosis at 30 days. On
      microscopic examination no histological injury to the capsule, urethra, rectal
      wall or nervous structures was identified. CONCLUSIONS: In this study, bilateral
      focal prostate ablation using LEDC was safe and had a favourable side-effects
      profile limited to transient minor events. LEDC ablation effectively spared
      adjacent structures as well as physiological functions in all the dogs.

PMID- 23879908
TI  - Cardiopulmonary exercise testing in major urological surgery: an old test; a new
      perspective; a potential application.

PMID- 23879909
TI  - Primary treatment of the prostate improves local palliation in men who ultimately
      develop castrate-resistant prostate cancer.
AB  - OBJECTIVES: To determine whether local treatment of primary prostate cancer gives
      palliative benefit to men who later develop castrate-resistant prostate cancer
      (CRPC). Local treatments of primary prostate cancer are defined as radical
      retropubic prostatectomy (RRP) or external beam radiation therapy (EBRT).
      PATIENTS AND METHODS: Patient records were reviewed in five different hospitals
      in Sydney, Australia, and 263 men with CRPC were identified. Eligible patients
      comprised men who had progressive disease during androgen deprivation therapy
      with castrate levels of testosterone. Clinical and pathological data were
      reviewed and evaluated using the chi-squared test and relative risk analysis to
      determine the relationship between previous local prostate treatment and
      complications secondary to local disease. The end-point was complications and
      morbidity attributed to cancer progression locally (i.e. from the prostate).
      RESULTS: Primary treatment of the prostate by either RRP or EBRT significantly
      reduces the incidence of local complications compared to no primary treatment
      (32.6% vs 54.6%; P = 0.001). RRP showed a significantly lower level of local
      complications compared to EBRT (20.0% vs 46.7%; P = 0.007). The most common local
      complications were bladder outlet obstruction (35.0%) and ureteric obstruction
      (15.2%). CONCLUSIONS: The present retrospective analysis supports the hypothesis
      that primary local prostatic treatment gives palliative benefit to men who later
      develop CRPC. RRP was associated with the lowest local complication rate
      experienced at the stage of metastatic disease.

PMID- 23879910
TI  - Predictors of biochemical failure in patients undergoing prostate whole-gland
      salvage cryotherapy: a novel risk stratification model.

PMID- 23879911
TI  - The interplay between obesity and the accuracy of prostate-specific antigen (PSA)
      for predicting prostate cancer.

PMID- 23879912
TI  - Managing the small renal mass: progress and opportunity.

PMID- 23879913
TI  - Predictive factors of complications after robot-assisted laparoscopic partial
      nephrectomy: a retrospective multicentre study.
AB  - OBJECTIVE: To analyse the predictive factors of complications after robot
      assisted laparoscopic partial nephrectomy (RALPN). MATERIALS AND METHODS: Data
      from six French institutions on 240 patients who underwent RALPN between 2009 and
      2011 were retrospectively reviewed. Clinical (age, body mass index, American
      Society of Anesthesiologists and Charlson comorbidity index scores, anticoagulant
      treatment), tumoral (size, R.E.N.A.L nephrometry score) and operative (surgeon
      experience, blood loss, opening of the collecting system, operating time)
      variables were considered. Univariate and multivariate regression models were
      used to assess the impact of these variables on the occurrence of global and
      major postoperative complications, classified according to the Clavien system.
      RESULTS: The median (range) patient age was 61 (26-83) years. Tumours were of low
      complexity in 62% of cases. Median (range) operating time, blood loss and warm
      ischaemia time were 161 (45-425) min, 100 (0-2500) mL and 20 (0-59) min,
      respectively. Postoperative complications occurred in 79 (33%) patients.
      Complications were >= grade III in 25 (10%) patients and were mostly
      haemorrhagic. In multivariate analysis, surgeon's experience (hazard ratio [HR]:
      2.14 [1.07-4.27], P = 0.03) and blood loss (HR: 1.002 [1.001-1.003], P < 0.001)
      were independent predictors of overall complications. When considering major
      complications, opening of the collecting system was the only factor that was
      significant (OR: 2.99 [1.2-7.26], P = 0.02). Nephrometry R.E.N.A.L. score was not
      associated with postoperative complications. CONCLUSION: In our experience, RALPN
      is associated with a 30% risk of postoperative complications; surgeon's
      experience, blood loss and opening of the collecting system were the three
      predictors of postoperative complications.

PMID- 23879914
TI  - Perioperative outcomes of robot-assisted nephroureterectomy for upper urinary
      tract urothelial carcinoma: a multi-institutional series.
AB  - OBJECTIVE: To review a multi-institutional series of robot-assisted
      nephroureterectomy (RANU) for management of upper urinary tract urothelial
      carcinoma (UUTUC) with respect to technique and perioperative outcomes. PATIENTS
      AND METHODS: Between May 2007 and July 2011, 43 RANU were performed at three
      institutions for UUTUC with review of perioperative outcomes. A three- or four
      armed robotic technique was used in all cases based on surgeon preference and the
      entirety of all procedures was performed using the robot-assisted technique.
      Single and two robot-docking techniques are described. RESULTS: The mean (range)
      operating time was 247 (128-390) min, blood loss was 131 (10-500) mL and the
      median (range) length of stay was 3 (2-87) days. Pathology was pTa in nine
      patients, pT1 in 14 patients, pT2 in three patients, pT3 in 15 patients and pT4
      in two patients. Lymph node dissection was performed in 22 patients (51%) with a
      mean (range) lymph node count of 11 (4-23). There were six postoperative
      complications: bleeding requiring a blood transfusion (grade II), splenic
      bleeding (grade IV), two cases of pneumonia (grade II) and two cases of
      rhabdomyolysis (grades II and IV). Nine recurrences (six bladder, two within the
      retroperitoneum and one in the contralateral collecting system) have been found
      to date on routine surveillance with a mean follow-up of 9 months. CONCLUSIONS:
      RANU is a feasible alternative to laparoscopic and open techniques. Particular
      steps of the operation including sutured closure of the cystotomy and regional
      lymphadenectomy are facilitated with the use of robot-assisted surgery. Long-term
      outcomes are necessary to assess the relative efficacy of these approaches to
      more established techniques; however, early perioperative outcomes appear
      promising.

PMID- 23879915
TI  - High-risk prostate cancer: too risky for the robotic learning curve.

PMID- 23879916
TI  - Robot-assisted vs traditional laparoscopic partial nephrectomy: the time for meta
      analysis has not yet arrived.

PMID- 23879917
TI  - Need to void and attentional process interrelationships.
AB  - OBJECTIVES: To determine whether a strong urge to void could affect a person's
      attentional performance. To determine whether an attentional task could decrease
      a strong urge to void a prospective study was performed. SUBJECTS AND METHODS:
      Healthy adults were asked to perform two neuropsychological tests, the modified
      Paced Auditory Serial Addition Test (mPASAT) and the Psychology Experiment
      Building Language Continuous Performance Test (pCPT), under two different
      conditions: no need to void, and a strong urge to void defined by a score of
      >70/100 mm on a visual analogue scale. RESULTS: In all, 21 healthy volunteers
      were included. There was no statistical difference between the mPASAT scores from
      the two sessions (P = 0.57). The mean total error score of the pCPT increased
      with the individual's urge to void (P = 0.043). The mean omission score
      decreased, but was not statistically different (P = 0.129), the commission error
      score increased with the urge to void (P = 0.017), with a shorter reaction time
      for the inter-stimuli intervals of 1 (P<0.001) and 2 s (P = 0.036), suggesting a
      tendency to hurry. CONCLUSIONS: A strong urge to void can alter attentional
      performance, with a tendency to hurry, in healthy volunteers taking part in a
      sustained attention test pCPT involving the use of the anterior cingulate cortex.

PMID- 23879918
TI  - Pelvic fracture urethral injuries in context.

PMID- 23879919
TI  - Effects of imatinib mesylate on the spontaneous activity generated by the guinea
      pig prostate.
AB  - What's known on the subject? and what does the study add?: Several studies have
      examined the functional role of tyrosine kinase receptors in the generation of
      spontaneous activity in various segments of the gastrointestinal and urogenital
      tracts through the application of its inhibitor, imatinib mesylate (Glivec(r)),
      but results are fairly inconsistent. This is the first study detailing the
      effects of imatinib mesylate on the spontaneous activity in the young and ageing
      prostate gland. As spontaneous electrical activity underlies the spontaneous
      rhythmic prostatic contractions that occur at rest, elucidating the mechanisms
      involved in the regulation of the spontaneous electrical activity and the
      resultant phasic contractions could conceivably lead to the identification of
      better targets and the development of more specific therapeutic agents to treat
      prostate conditions. OBJECTIVE: To investigate the effect of imatinib mesylate, a
      tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical
      and contractile activity in the young and ageing guinea-pig prostate. MATERIALS
      AND METHODS: Standard tension and intracellular recording were used to measure
      spontaneous contractions and slow waves, respectively from the guinea-pig
      prostate at varying concentrations of imatinib mesylate (1-50 MUm). RESULTS:
      Imatinib mesylate (1-10 MUm), did not significantly affect slow waves recorded in
      the prostate of both age groups but at 50 MUm, the amplitude of slow waves from
      the ageing guinea-pig prostate was significantly reduced (P < 0.05, n = 5). In
      contrast, the amplitude of contractions across all concentrations in the young
      guinea-pig prostate was reduced to between 35% and 41% of control, while the
      frequency was reduced to 15.7% at 1 MUm (n = 7), 49.8% at 5 MUm (n = 10), 46.2%
      at 10 MUm (n = 7) and 53.1% at 50 MUm (n = 5). Similarly, imatinib mesylate
      attenuated the amplitude and slowed the frequency of contractions in ageing
      guinea-pigs to 5.15% and 3.3% at 1 MUm (n = 6); 21.1% and 20.8% at 5 MUm (n = 8);
      58.4% and 8.8% at 10 MUm (n = 11); 72.7% and 60% at 50 MUm (n = 5). CONCLUSIONS:
      A significant reduction in contractions but persistence of slow waves suggests
      imatinib mesylate may affect the smooth muscle contractile mechanism. Imatinib
      mesylate also significantly reduced contractions in the prostates of younger
      guinea pigs more than older ones, which is consistent with the notion that the
      younger guinea-pig prostate is more reliant on the tyrosine-dependent pacemaker
      ability of interstitial cells of Cajal-like prostatic interstitial cells.

PMID- 23879920
TI  - Low differentiated microvascular density and low expression of platelet-derived
      growth factor-BB (PDGF-BB) predict distant metastasis and poor prognosis in clear
      cell renal cell carcinoma.
AB  - OBJECTIVE: To examine the prognostic significance of the expression of platelet
      derived growth factor-BB (PDGF-BB) and differentiated microvascular density (MVD)
      in patients with clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS:
      We used the vascular marker cluster of differentiation 34 (CD34) to identify
      tumour blood vessels. The expression of PDGF-BB and CD34 was detected by
      immunohistochemistry (IHC) in tissue microarrays (TMAs) from 100 ccRCCs.
      Prognostic effects of individual parameters were calculated using Cox regression
      models and Harrell's concordance index (c-index). RESULTS: Higher grade and more
      advanced stage ccRCCs had significantly less PDGF-BB expression and
      differentiated MVD (P < 0.05). Higher PDGF-BB expression was an independent
      prognostic factor for longer survival, and moreover, the final model built by the
      addition of PDGF-BB expression improved the predictive accuracy for disease-free
      survival (c-index 0.707) compared with the clinicopathological-based model (c
      index 0.695). PDGF-BB expression was positively associated with differentiated
      MVD assessed by Spearman correlation and factor analysis (r = 0.634, P < 0.001).
      CONCLUSION: PDGF-BB is as a novel and promising prognostic marker and
      antiangiogenic therapeutic target for the treatment of ccRCC.

PMID- 23879921
TI  - Reply: To PMID 22924860.

PMID- 23879922
TI  - Are there long-term effects of extracorporeal shockwave lithotripsy in paediatric
      patients?

PMID- 23879923
TI  - Reply: To PMID 23879924.

PMID- 23879924
TI  - De novo erectile dysfunction after anterior urethroplasty: a systematic review
      and meta-analysis.

PMID- 23879925
TI  - Newer and novel artificial urinary sphincters (AUS): the development of
      alternatives to the current AUS device.

PMID- 23879927
TI  - New metabolic pathway for converting blasticidin S in Aspergillus flavus and
      inhibitory activity of aflatoxin production by blasticidin S metabolites.
AB  - Blasticidin S, a protein synthesis inhibitor, inhibits aflatoxin production of
      Aspergillus flavus without affecting fungal growth. Analysis of metabolites in
      blasticidin S-treated A. flavus using quadrupole time-of-flight liquid
      chromatography-mass spectrometry showed that blasticidin S was metabolized into a
      novel metabolite, N-acetyldeaminohydroxyblasticidin S. Conversion of blasticidin
      S to N-acetyldeaminohydroxyblasticidin S via deaminohydroxyblasticidin S or N
      acetylblasticidin S was observed in in vivo and in vitro A. flavus systems.
      Blasticidin S and N-acetylblasticidin S inhibited the growth of Aspergillus niger
      strongly and weakly, respectively, but deaminohydroxyblasticidin S and N
      acetyldeaminohydroxyblasticidin S did not inhibit its growth. On the other hand,
      deaminohydroxyblasticidin S sustained the inhibition of aflatoxin production
      whereas N-acetylblasticidin S and N-acetyldeaminohydroxyblasticidin S did not.
      These results suggest that the free amino group at C-13 of blasticidin S and
      deaminohydroxyblasticidin S may be important for the inhibitory activity of
      aflatoxin production. 

PMID- 23879926
TI  - Echo-power estimation from log-compressed video data in dynamic contrast-enhanced
      ultrasound imaging.
AB  - Ultrasound (US) scanners typically apply lossy, non-linear modifications to the
      US data for visualization purposes. The resulting images are then stored as
      compressed video data. Some system manufacturers provide dedicated software for
      quantification purposes to eliminate such processing distortions, at least
      partially. This is currently the recommended approach for quantitatively
      assessing changes in contrast-agent concentration from clinical data. However,
      the machine-specific access to US data and the limited set of analysis
      functionalities offered by each dedicated-software package make it difficult to
      perform comparable analyses with different US systems. The objective of this work
      was to establish if linearization of compressed video images obtained with an
      arbitrary US system can provide an alternative to dedicated-software analysis of
      machine-specific files for the estimation of echo-power. For this purpose, an
      Aplio 50 system (Toshiba Medical Systems, Tochigi, Japan), coupled with dedicated
      CHI-Q (Contrast Harmonic Imaging Quantification) software by Toshiba Medical
      Systems, was used. Results were compared with two approaches that apply
      algorithms to estimate relative echo-power from compressed video images:
      commercially available VueBox software by Bracco Suisse SA (Geneva, Switzerland)
      and in-laboratory software called PixPower. The echo-power estimated by CHI-Q
      analysis indicated a strong linear relationship versus agent concentration in
      vitro (R(2) >= 0.9996) for dynamic range (DR) settings of DR60 and DR80, with
      slopes between 9.22 and 9.57 dB/decade (p = 0.05). These values approach the
      theoretically predicted dependence of 10.0 dB/decade (equivalent to 3 dB for each
      concentration doubling). Echo-power estimations obtained from compressed video
      images with VueBox and PixPower also exhibited strong linear proportionality with
      concentration (R(2) >= 0.9996), with slopes between 9.30 and 9.68 dB/decade (p =
      0.05). On an independent in vivo data set (N = 24), the difference in echo-power
      estimation between CHI-Q and each of the other two approaches was calculated
      after excluding regions that contain pixels affected by saturated or thresholded
      pixel values. The mean difference in estimates (expressed in decibels) was -0.25
      dB between VueBox and CHI-Q (95% confidence interval: -0.75 to 0.26 dB) and -0.17
      dB between PixPower and CHI-Q (95% confidence interval: -0.67 to 0.13 dB). To
      achieve linearization of data, one of the approaches (VueBox) requires
      calibration files provided by the software manufacturer for each machine type and
      setting. The other (PixPower) requires empirical correction of the imaging
      dynamic range based on ground truth data. These requirements could potentially be
      removed if US system manufacturers were willing to make relevant information on
      the applied processing publically available. Reliable echo-power estimation from
      linearized data would facilitate inclusion of different US systems in
      multicentric studies and more widespread implementation of emerging techniques
      for quantitative analysis of contrast ultrasound.

PMID- 23879928
TI  - Evaluation of association between airway hyperresponsiveness, asthma control
      test, and asthma therapy assessment questionnaire in asthmatic children.
AB  - BACKGROUND: Achieving asthma control is a major challenge in children, otherwise
      symptoms perception remain poor especially at this age. The aim of this study is
      to evaluate the relationship between Asthma Control Test (ACTTM), Asthma Therapy
      Assessment Questionnaire (ATAQTM) and exercise-induced bronchospasm (EIB).
      METHODS: We studied 80 asthmatic children. Airways hyperresponsiveness (AHR) was
      assessed by exercise-induced bronchospasm (Balke Protocol). Asthma control was
      evaluated using two questionnaires in all subjects: ACT (composed by Childhood
      ACT and ACT) and ATAQ. In addition the use of short acting beta 2 agonist agents
      (SABAs) was assessed for each patient. Non-parametric variables were compared by
      Chi Square Test. Binomial logistic regression was performed to estimate the two
      questionnaires Odds Ratio (OR) in finding AHR. RESULTS: We have found that ATAQ
      has a sensitivity and a specificity of 0.72 and 0.45 respectively; instead, ACT
      has a sensitivity and a specificity of 0.5 and 0.39 respectively in evaluating
      AHR. Patients with uncontrolled asthma according to ATAQ revealed a significant
      higher percentage of AHR compared with ACT (72% vs 50%, p < 0.01).Confirming this
      finding, patients declaring uncontrolled asthma to ATAQ have a significantly
      higher percentage (34%) of frequent SABAs use than the group with uncontrolled
      asthma to ACT (21%) (p <0.01).Binomial logistic regression shows how a test
      revealing uncontrolled asthma is associated with the increasing odds of having
      AHR according to ATAQ (OR = 3.8, p = 0.05), not to ACT (OR = 0.2, p = 0.1).
      CONCLUSIONS: Our results show that ATAQ reflects AHR and asthma control better
      than ACT. Children with uncontrolled asthma according to ATAQ have higher odds of
      having AHR and use of rescue medications (SABAs) compared to patients declaring
      uncontrolled asthma according to ACT. However both questionnaires are not
      sufficient alone to fully evaluate asthma control in children and it is always
      necessary to perform functional tests and investigate patients lifestyle, drug
      use and other important data that a simple questionnaire is not able to point
      out.

PMID- 23879929
TI  - Microcirculation and its relation to continuous subcutaneous glucose sensor
      accuracy in cardiac surgery patients in the intensive care unit.
AB  - OBJECTIVE: Continuous glucose monitoring could be helpful for glucose regulation
      in critically ill patients; however, its accuracy is uncertain and might be
      influenced by microcirculation. We investigated the microcirculation and its
      relation to the accuracy of 2 continuous glucose monitoring devices in patients
      after cardiac surgery. METHODS: The present prospective, observational study
      included 60 patients admitted for cardiac surgery. Two continuous glucose
      monitoring devices (Guardian Real-Time and FreeStyle Navigator) were placed
      before surgery. The relative absolute deviation between continuous glucose
      monitoring and the arterial reference glucose was calculated to assess the
      accuracy. Microcirculation was measured using the microvascular flow index,
      perfused vessel density, and proportion of perfused vessels using sublingual
      sidestream dark-field imaging, and tissue oxygenation using near-infrared
      spectroscopy. The associations were assessed using a linear mixed-effects model
      for repeated measures. RESULTS: The median relative absolute deviation of the
      Navigator was 11% (interquartile range, 8%-16%) and of the Guardian was 14%
      (interquartile range, 11%-18%; P = .05). Tissue oxygenation significantly
      increased during the intensive care unit admission (maximum 91.2% [3.9] after 6
      hours) and decreased thereafter, stabilizing after 20 hours. A decrease in
      perfused vessel density accompanied the increase in tissue oxygenation.
      Microcirculatory variables were not associated with sensor accuracy. A lower
      peripheral temperature (Navigator, b = -0.008, P = .003; Guardian, b = -0.006, P
      = .048), and for the Navigator, also a higher Acute Physiology and Chronic Health
      Evaluation IV predicted mortality (b = 0.017, P < .001) and age (b = 0.002, P =
      .037) were associated with decreased sensor accuracy. CONCLUSIONS: The results of
      the present study have shown acceptable accuracy for both sensors in patients
      after cardiac surgery. The microcirculation was impaired to a limited extent
      compared with that in patients with sepsis and healthy controls. This impairment
      was not related to sensor accuracy but the peripheral temperature for both
      sensors and patient age and Acute Physiology and Chronic Health Evaluation IV
      predicted mortality for the Navigator were.

PMID- 23879930
TI  - Port-access redo mitral valve surgery in a 13-year-old child.

PMID- 23879931
TI  - Effect of one-stop hybrid coronary revascularization on postoperative renal
      function and bleeding: a comparison study with off-pump coronary artery bypass
      grafting surgery.
AB  - OBJECTIVES: Although 1-stop hybrid coronary revascularization offers potential
      benefits for selected patients with multivessel coronary artery disease, the
      exposure to contrast dye and potent antiplatelet drugs could increase the risk of
      postoperative acute kidney injury and coagulopathy. The goal of the present study
      was to compare the measures of renal function, postoperative bleeding, and
      transfusion requirements in patients undergoing hybrid revascularization compared
      with off-pump coronary artery bypass grafting (CABG). METHODS: We retrospectively
      analyzed the data from 141 consecutive patients who had undergone 1-stop hybrid
      coronary revascularization from June 2007 to January 2011. Propensity score
      matching with 141 off-pump CABG patients from our surgical database was performed
      for comparison. The change in renal function, cumulative chest tube drainage, and
      clinical outcome parameters were compared between the 2 groups. RESULTS: Compared
      with off-pump CABG, patients undergoing hybrid revascularization had
      significantly less chest tube drainage at 12 hours after surgery (P = .04) and
      for the total amount during the postoperative period (P < .001) and required
      fewer blood transfusions (P = .001). The hybrid group had a higher incidence of
      acute kidney injury, but this did not reach statistical significance (25.2% vs
      17.6%, P = .13). The hybrid group required less inotropic and vasoactive support,
      had fewer respiratory complications, required a shorter time of mechanical
      support, and had a decreased length of intensive care unit stay. CONCLUSIONS:
      Compared with off-pump CABG, 1-stop hybrid coronary revascularization was
      associated with benefits such as less postoperative bleeding and blood
      transfusion requirements without significantly increasing the additional risk of
      acute kidney injury.

PMID- 23879932
TI  - Aortic diameter predicts acute type A aortic dissection in patients with Marfan
      syndrome but not in patients without Marfan syndrome.
AB  - OBJECTIVES: Among the parameters for surveillance of patients at risk of acute
      type A aortic dissection, the aortic size has been considered a cardinal factor.
      Preventive surgery of the aorta in asymptomatic patients on the basis of size
      alone is still controversial in patient populations lacking other risk factors
      for aortic dissection. The aim of the present study was to assess the value of
      the aortic diameter as a current criterion for elective aortic surgery to prevent
      the development of aortic dissection in patients without and with Marfan syndrome
      (MFS). METHODS: We reviewed the data from patients diagnosed with acute type A
      aortic dissection from December 1994 to March 2009 at our institute. A total of
      237 patients who presented with acute type A aortic dissection were enrolled, of
      whom 31 were diagnosed with MFS. RESULTS: The maximal ascending aorta size was
      46.7 mm (range, 42.9-51.6) in non-MFS patients and 58.5 mm (range, 43.8-64.9) in
      MFS patients (P < .001). Two thirds (74%) of the MFS patients had a maximal
      aortic root size of >=45 mm. However, 87% of the 206 non-MFS patients had an
      aortic diameter <55 mm. Non-MFS patients presenting with an aortic size <55 mm
      developed aortic dissection at a younger age and had a higher body mass index
      than those with an aortic size >=55 mm. CONCLUSIONS: Type A aortic dissection
      occurs in smaller aortas in non-MFS patients compared with those with MFS.

PMID- 23879933
TI  - Risk factors for preoperative periventricular leukomalacia in term neonates with
      hypoplastic left heart syndrome are patient related.
AB  - BACKGROUND: Preoperative brain injury is common in neonates with complex
      congenital heart disease. Increasing evidence suggests a complex interaction of
      prenatal and postnatal risk factors for development of brain white matter injury,
      called periventricular leukomalacia (PVL), in neonates with complex congenital
      heart disease. To date, there remains a limited understanding of the risk factors
      contributing to preoperative PVL in hypoplastic left heart syndrome (HLHS).
      METHODS: Neonates with HLHS or HLHS variants from 3 prospective magnetic
      resonance imaging studies (2003-2010) were selected for this cohort. Preoperative
      brain magnetic resonance imaging was performed the morning of the surgery.
      Stepwise multilogistic regression of patient characteristics, mode of delivery
      (cesarean section vs vaginal), time of diagnosis (prenatal vs postnatal), HLHS
      subtypes, brain total maturation score, time to surgery, individual averaged
      daily preoperative blood gases, and complete blood cell count values was used to
      determine significant associations. RESULTS: A total of 57 neonates with HLHS
      were born at 38.7 +/- 2.3 weeks; 86% (49/57) had a prenatal diagnosis, with 31%
      (18/57) delivered by cesarean section. HLHS with aortic atresia (AA) was common
      in this cohort, 71% (41/57). Preoperative PVL was identified in 19% (11/57). Male
      patients with AA (P = .004) were at higher risk for PVL. Lower total brain
      maturation score was also identified as a strong predictor for preoperative PVL
      (P = .005). CONCLUSIONS: In neonates with HLHS, nonmodifiable patient-related
      factors, including male sex with AA (lack of antegrade blood flow) and lower
      total brain maturation score, placed neonates at the greatest risk for
      preoperative white matter injury.

PMID- 23879934
TI  - Timing of complete repair of non-ductal-dependent tetralogy of Fallot and short
      term postoperative outcomes, a multicenter analysis.
AB  - OBJECTIVE: There is cross-center variability with regard to timing repair of non
      ductal-dependent tetralogy of Fallot (TOF). We hypothesized that earlier repair
      in the neonatal period is associated with increased mortality and morbidity.
      METHODS: This was a retrospective analysis of the Pediatric Health Information
      System of tetralogy of Fallot patients undergoing complete repair from 2004
      through 2010 between the ages of 1 day to younger than 19 years. Patients with
      pulmonary valve atresia, those who received prostaglandin during hospital
      admission, and those who underwent prior shunt palliation were excluded. RESULTS:
      A total of 4698 patients met our inclusion criteria, of whom 202 were younger
      than 30 days old (group A), 861 were 31 to 90 days old (group B), 1796 were 91 to
      180 days old (group C), and 1839 were older than 180 days (group D). In-hospital
      mortality, intensive care unit length of stay, and total hospital length of stay
      were significantly higher in group A. Patients in group A had a significantly
      increased postoperative requirement for mechanical ventilation, intravenous blood
      pressure support, medical diuresis, extracorporeal membrane oxygenation,
      gastrostomy tube insertion, heart catheterization, and surgical revision.
      Significant institutional variability was noted for timing of TOF complete
      repair, with one third of the centers performing 75% of the repairs at younger
      than 30 days old. The institutional approach to timing TOF complete repair showed
      no relation to surgical volume. CONCLUSIONS: Across all centers analyzed, primary
      neonatal elective TOF repair (<30 days of age) is associated with significantly
      higher postoperative in-hospital morbidity and mortality, although a few centers
      have shown an ability to use this strategy with excellent survivability.

PMID- 23879935
TI  - Polyunsaturated fatty acid relatively decreases cholesterol content in THP-1
      macrophage-derived foam cell: partly correlates with expression profile of CIDE
      and PAT members.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFAs) have positive effect on the
      regulation of plasma lipids. But the mechanism for them to modulate lipid
      homeostasis in macrophage is still unclear. In this study, we employed PUFA to
      pretreat macrophages and evaluated the variations of lipid droplet (LD) content,
      lipid composition, and expressions of LD-associated genes in macrophage-derived
      foam cells. METHOD: THP-1-derived macrophages or human peripheral blood monocyte
      derived macrophages were pre-treated with four non-esterified fatty acids (NEFAs)
      separately: saturated fatty acid (SFA)-palmitic acid (PA), monounsaturated fatty
      acids (MUFAs)-oleic acid (OA), PUFAs-linoleic acid (LA) and eicosapentaenoic acid
      (EPA). Intracellular lipid content and cholesterol efflux were analyzed in THP-1
      macrophage-derived foam cells. Related gene expressions were detected by
      quantitative real-time PCR. RESULTS: PUFA pre-treatment reduced cholesterol
      content in foam cells and increased cholesterol efflux to lipid-free apoAI in
      conditioned medium compared with PA or OA group. Cell death-inducing DFF45 like
      effector (CIDE) and Perilipin-Adipophilin-TIP47 (PAT) family members, as LD
      associated proteins, showed specific gene expression profiles after PUFA pre
      treatment. These results may help to explain the process of lipid metabolism
      within foam cells. CONCLUSION: PUFA (LA or EPA) had a potential protective effect
      against cholesterol accumulation. The specific expressions of CIDE and PAT genes
      may provide clues to explore the protective mechanism of PUFA in foam cells.

PMID- 23879936
TI  - Finding your way through EOL challenges in the ICU using Adaptive Leadership
      behaviours: A qualitative descriptive case study.
AB  - OBJECTIVE: Using the Adaptive Leadership framework, we describe behaviours that
      providers used while interacting with family members facing the challenges of
      recognising that their loved one was dying in the ICU. RESEARCH METHODOLOGY: In
      this prospective pilot case study, we selected one ICU patient with end-stage
      illness who lacked decision-making capacity. Participants included four family
      members, one nurse and two physicians. The principle investigator observed and
      recorded three family conferences and conducted one in-depth interview with the
      family. Three members of the research team independently coded the transcripts
      using a priori codes to describe the Adaptive Leadership behaviours that
      providers used to facilitate the family's adaptive work, met to compare and
      discuss the codes and resolved all discrepancies. FINDINGS: We identified
      behaviours used by nurses and physicians that facilitated the family's ability to
      adapt to the impending death of a loved one. Examples of these behaviours include
      defining the adaptive challenges for families and foreshadowing a poor prognosis.
      CONCLUSIONS: Nurse and physician Adaptive Leadership behaviours can facilitate
      the transition from curative to palliative care by helping family members do the
      adaptive work of letting go. Further research is warranted to create knowledge
      for providers to help family members adapt.

PMID- 23879937
TI  - Studies on time of death estimation in the early post mortem period --
      application of a method based on eyeball temperature measurement to human bodies.
AB  - This paper presents a verification of the thermodynamic model allowing an
      estimation of the time of death (TOD) by calculating the post mortem interval
      (PMI) based on a single eyeball temperature measurement at the death scene. The
      study was performed on 30 cases with known PMI, ranging from 1h 35min to 5h
      15min, using pin probes connected to a high precision electronic thermometer
      (Dostmann-electronic). The measured eye temperatures ranged from 20.2 to 33.1
      degrees C. Rectal temperature was measured at the same time and ranged from 32.8
      to 37.4 degrees C. Ambient temperatures which ranged from -1 to 24 degrees C,
      environmental conditions (still air to light wind) and the amount of hair on the
      head were also recorded every time. PMI was calculated using a formula based on
      Newton's law of cooling, previously derived and successfully tested in
      comprehensive studies on pigs and a few human cases. Thanks to both the
      significantly faster post mortem decrease of eye temperature and a residual or
      nonexistent plateau effect in the eye, as well as practically no influence of
      body mass, TOD in the human death cases could be estimated with good accuracy.
      The highest TOD estimation error during the post mortem intervals up to around 5h
      was 1h 16min, 1h 14min and 1h 03min, respectively in three cases among 30, while
      for the remaining 27 cases it was not more than 47min. The mean error for all 30
      cases was +/-31min. All that indicates that the proposed method is of quite good
      precision in the early post mortem period, with an accuracy of +/-1h for a 95%
      confidence interval. On the basis of the presented method, TOD can be also
      calculated at the death scene with the use of a proposed portable electronic
      device (TOD-meter). 

PMID- 23879938
TI  - DCJ-indel and DCJ-substitution distances with distinct operation costs.
AB  - BACKGROUND: Classical approaches to compute the genomic distance are usually
      limited to genomes with the same content and take into consideration only
      rearrangements that change the organization of the genome (i.e. positions and
      orientation of pieces of DNA, number and type of chromosomes, etc.), such as
      inversions, translocations, fusions and fissions. These operations are
      generically represented by the double-cut and join (DCJ) operation. The distance
      between two genomes, in terms of number of DCJ operations, can be computed in
      linear time. In order to handle genomes with distinct contents, also insertions
      and deletions of fragments of DNA - named indels - must be allowed. More powerful
      than an indel is a substitution of a fragment of DNA by another fragment of DNA.
      Indels and substitutions are called content-modifying operations. It has been
      shown that both the DCJ-indel and the DCJ-substitution distances can also be
      computed in linear time, assuming that the same cost is assigned to any DCJ or
      content-modifying operation. RESULTS: In the present study we extend the DCJ
      indel and the DCJ-substitution models, considering that the content-modifying
      cost is distinct from and upper bounded by the DCJ cost, and show that the
      distance in both models can still be computed in linear time. Although the
      triangular inequality can be disrupted in both models, we also show how to
      efficiently fix this problem a posteriori.

PMID- 23879939
TI  - [What have we learned from the expert consensus of antiplatelet therapy in
      cardiovascular disease?].

PMID- 23879940
TI  - [Chinese expert recommendation on stroke risk stratification in nonvalvular
      atrial fibrillation patients].

PMID- 23879941
TI  - [Expert consensus of antiplatelet therapy in cardiovascular disease].

PMID- 23879942
TI  - [Short-term prognosis and risk factors of ventricular septal rupture following
      acute myocardial infarction].
AB  - OBJECTIVE: To analyze the short-term prognosis and risk factors of ventricular
      septal rupture (VSR) following acute myocardial infarction (AMI). METHODS: A
      total of 70 consecutive VSR patients following AMI hospitalized in our hospital
      from January 2002 to October 2010 were enrolled in this study. We compared the
      clinical characteristics of patients with VSR who survived <= 30 days (n = 39)
      and survived > 30 days (n = 31) post AMI. A short-term prognosis index of VSR
      (SPIV) was established based on the logistic regression analysis. RESULTS: The
      single factor analysis showed that the risk factors of death within 30 days of
      VSR patients were female, anterior AMI, Killip class 3 or 4, apical VSR and non
      aneurysm (all P < 0.05). Logistic regression analysis revealed that female (P =
      0.013), anterior AMI (P = 0.023), non-aneurysm (P = 0.023), non-diabetes (P =
      0.009), Killip class 3 or 4 (P = 0.022) and time from AMI to VSR less than 4 days
      (P = 0.027) were independent risk determinants for death within 30 days post VSR.
      Patients with SPIV >= 9 were associated with high risk [77.4% (24/31)] of dying
      within 30 days post AMI. SPIV <= 8 were associated with low risk as the 30 days
      mortality is 28.6% (8/28). CONCLUSION: Female gender, anterior AMI, non-aneurysm,
      non-diabetes, Killip class 3 or 4 and time from AMI to VSR less than 4 days are
      independent risk factors of short-term mortality of VSR.

PMID- 23879943
TI  - [An initial study on the feasibility of diagnosing myocardial ischemia with CT
      first-pass myocardial perfusion imaging at rest].
AB  - OBJECTIVE: To assess the feasibility and accuracy of CT first-pass myocardial
      perfusion imaging (CT first-pass MPI) at rest for diagnosis of myocardial
      ischemia. Results of adenosine-induced myocardial perfusion scintigraphy (MPS)
      were used as gold standard. METHODS: Twenty-two patients with suspected or
      diagnosed coronary artery disease (CAD) were included and CT coronary angiography
      (CTCA) and MPS were performed within 2 weeks. CT first-pass MPI detected
      myocardial ischemia results through analyzing the raw date of CTCA were compared
      with MPS results. RESULTS: The sensibility, specificity, positive predictive
      value (PPV), negative predictive value (NPV) and accuracy of CT first-pass MPI at
      rest for detecting myocardial ischemia were 92% (12/13), 78% (7/9), 86% (12/14),
      88% (7/8) and 86% (19/22), respectively. CONCLUSION: CT first-pass MPI at rest
      could detect myocardial ischemia with an accuracy similar to that of MPS.

PMID- 23879944
TI  - [Effects of trimetazidine therapy on left ventricular function after percutaneous
      coronary intervention].
AB  - OBJECTIVE: To explore the effects of trimetazidine therapy on left ventricular
      (LV) function after percutaneous coronary intervention (PCI). METHODS: A total of
      106 patients with unstable angina pectoris underwent successful elective PCI were
      randomly assigned to standard therapy group (control, n = 55) or trimetazidine
      group (n = 51, 60 mg trimetazidine loading dose prior to PCI followed by 20 mg
      Tid after PCI on top of standard therapy). cTnI level was measured before and at
      16-18 hours after PCI. LV function was evaluated by echocardiography and major
      adverse cardiac events (MACE, including death, re-infarction and target vessel
      revascularization) at 12 months after PCI was compared between the two groups.
      RESULTS: Post procedural cTnI level increased from [0.02 (0.01, 0.03)] ug/L at
      baseline to [0.11 (0.07, 0.13)] ug/L (P < 0.05) at 16-18 hours in the
      trimetazidine group, while [0.02(0.01, 0.03)] ug/L to [1.31(0.44, 2.31)] ug/L in
      the control group (P < 0.05). Post procedural cTnI level was significantly
      reduced in the trimetazidine group compared to the control group (P < 0.05). At
      12 months follow-up, left ventricular ejection fraction in the trimetazidine
      group was significantly higher than in control group [(65.65 +/- 3.94)% vs.
      (62.29 +/- 3.06)%, P < 0.01] while incidence of MACE was similar between the two
      groups. CONCLUSION: Trimetazidine can reduce the post-PCI cTnI release and
      improve left ventricular function after PCI in patients with unstable angina
      pectoris.

PMID- 23879945
TI  - [Efficacy of subgroup mouse bone mesenchymal stem cells on mobilizing autologous
      cardiac stem cells and repairing ischemic myocardial tissue].
AB  - OBJECTIVE: To search for the bone mesenchymal stem cell (MSC) subgroup which
      might be more effective on repairing myocardial damage. METHODS: In this
      experiment, four MSC subgroups were defined based on the surface differentiation
      antigen detection of mouse bone mesenchymal stem cells (mBMSCs): SCA
      1(+)/CD45(+)/CD31(+), SCA-1(+)/CD45(+)/CD31(-), SCA-1(+)/CD45(-)/CD31(-) and SCA
      1(+)/CD45(-)/CD31(+). These subgroup cells and unselected mBMSCs were injected
      into infarcted mouse via tail vein. Echocardiographic heart function measurement
      and in vivo DiR-labeled stem cells imaging were performed at 48 h after
      injection. In situ C-kit (a flag antigen of cardiac stem cells) and cardiac
      specific differentiation antigen immunohistochemistry detection was made in the
      infarcted myocardium. RESULTS: The capacity of the SCA-1(+)/CD45(+)/CD31(+) cells
      on improving heart function was significantly higher than other cell groups (all
      P < 0.05). In vivo imaging showed that the mean fluorescence intensity of the SCA
      1(+)/CD45(+)/CD31(+) cells was also higher than other cell groups (all P < 0.05).
      Number of cardiac stem cells in the infracted myocardium was significantly
      increased after the injection of all subgroup cells and unsorted mBMSCs cells for
      48 h compared untreated infracted myocardium. The capacity of mobilizing cardiac
      stem cells is as follows: SCA-1(+)/CD45(+)/CD31(+) >SCA-1(+)/CD45(-)/CD31(+) >SCA
      1(+)/CD45(-)/CD31(-) >SCA-1(+)/CD45(+)/CD31(-). CONCLUSION: The SCA
      1(+)/CD45(+)/CD31(+) subgroups of mBMSCs exhibites the highest capacity to
      improve cardiac function after myocardial infarction and to mobilize autologous
      cardiac stem cells compared with other mBMSCs subgroups and unsorted mBMSCs
      cells.

PMID- 23879946
TI  - [Risk factors for hypertension and impact of postoperative hypertension on medium
      survival after heart transplantation].
AB  - OBJECTIVE: To access the prevalence and risk factors for hypertension after heart
      transplantation (HT), and the impact of post-transplant hypertension on medium
      term survival among HT patients. METHODS: Data from 265 consecutive patients
      underwent HT between June 2004 and May 2012 in Fuwai hospital and survived for at
      least 6 months were retrospectively analyzed. Hypertension was defined as
      systolic pressure >= 140 mm Hg (1 mm Hg = 0.133 kPa) and/or diastolic pressure >=
      90 mm Hg or current treatment with antihypertensive drugs. Patients were divided
      into post-HT hypertension group and non-hypertension group. Logistic regression
      analysis was used to determine preoperative and postoperative risk factors for
      hypertension after HT. Kaplan-Meier method and log rank test were used for
      survival analysis. RESULTS: Hypertension was present in 17.4% (46/265) patients
      before HT and in 57.4% (152/265) patients post HT. The median follow-up time was
      37 months (20 - 57 months). Logistic regression analysis showed that male gender
      (OR: 2.27, 95%CI: 1.16 - 4.42, P < 0.05), history of pre-HT hypertension (OR:
      2.22, 95%CI: 1.05 - 4.71, P < 0.05), and cyclosporine A based immunosuppressive
      therapy (OR: 2.54, 95%CI: 1.51 - 4.29, P < 0.01) were independent risk factors
      for the development of post-HT hypertension. At the end of 1, 3, 5 years, the
      survival rate of heart transplant patients by Kaplan-Meier method estimation were
      100%, 97.2%, 86.7% in post-HT hypertension group; 98.1%, 93.8%, 93.8% in non
      hypertension group. Log rank test displayed that there was no significant
      difference between the two survival curves (P > 0.05). CONCLUSIONS: Hypertension
      is a frequent comorbidity after HT. Male gender, pre-HT hypertension together
      with cyclosporine A based immunosuppressive therapy are independent predictors
      for the development of post-HT hypertension. By adjusting the controllable risk
      factors and active control of blood pressure, the medium-term survival is similar
      between patients with or without postoperative hypertension in this cohort.

PMID- 23879947
TI  - [Impact of systolic blood pressure on visit-to-visit blood pressure variability
      in middle-aged and elderly people].
AB  - OBJECTIVE: To observe the impact of systolic blood pressure (SBP) on visit-to
      visit blood pressure variability (BPV) in middle-aged and elderly people.
      METHODS: Visit-to-visit BPV was determined in 5440 workers in the Kailuan study
      cohort from 2006 to 2007. The subjects were >= 40 years-old and had no history of
      stroke, transient ischemic attack or myocardial infarction. Participants were
      divided into five groups according to different levels of SBP. Linear regression
      was used to analyze the related factors which might affect BPV. RESULTS: Mean
      systolic BPV of all subjects was 10.35 mm Hg [coefficient of variation (CV
      7.96%)]. The mean systolic BPV of males was 10.54 mm Hg (CV 7.90%) while the mean
      SBPV of females was 10.06 mm Hg (CV 7.90%). The BPV of males was significant
      higher than that of females (P < 0.001). CV of SBP was similar between males and
      females. Furthermore, higher SBP was associated with higher BPV. There were
      significant differences in BPV between different groups with different levels of
      SBP (P < 0.001). Linear regression analysis demonstrated that SBP, age, gender,
      high-sensitivity C-reactive protein (hsCRP) were affecting factors of BPV. Twenty
      mm Hg SBP increase was linked with 2.02 mm Hg BPV increase and 0.388%CV increase.
      Age increase of 1 year was associated with 0.044 mm Hg BPV increase and 0.029% CV
      increase. CONCLUSION: SBP, age, gender and hsCRP are important factors affecting
      BPV in middle-aged and elderly people. Higher SBP is closely related to greater
      BPV in this cohort.

PMID- 23879948
TI  - [Chronic effects of 100 mg/2 hours recombinant tissue-type plasminogen activator
      therapy regimen for patients with acute pulmonary thromboembolism].
AB  - OBJECTIVE: To evaluate the efficacy and safety of 100 mg/2 hours recombinant
      tissue-type plasminogen activator (rt-PA) regimen for treating patients with
      acute pulmonary thromboembolism (PE) by observing long-term clinical outcome
      including recurrent pulmonary embolism, chronic thromboembolic pulmonary
      hypertension (CTEPH) and other complications. METHODS: Data of 43 consecutive
      patients with acute high-risk and intermediate-risk PE treated with intravenous
      rt-PA (100 mg/2 hours) were prospectively analyzed. Median follow-up post
      thrombolysis was (15.6 +/- 11.4) months. The endpoints of the study were PE
      recurrence, death related to PE and onset CTEPH. RESULTS: After rt-PA therapy,
      pulse pressure increased [(46.7 +/- 9.5) mm Hg(1 mm Hg = 0.133 kPa)vs. (41.9 +/-
      11.3) mm Hg, P = 0.007], heart rate and respiratory rate decreased [(84.2 +/-
      14.7) bpm vs.(93.3 +/- 17.7) bpm, P < 0.001; (20.2 +/- 2.4) bpm vs. (23.2 +/-
      4.1) bpm, P < 0.001, respectively], tricuspid annular plane systolic excursion
      increased [(18.7 +/- 3.1) mm vs. (15.9 +/- 3.9) mm, P < 0.001] and right
      ventricle transverse diameter [(34.0 +/- 3.6) mm vs. (36.8 +/- 4.4) mm, P <
      0.001]. PO2, SO2 and P(A-a)O2 improved [ (87.9 +/- 17.8) mm Hg vs. (73.4 +/-
      20.1) mm Hg, P < 0.001; 96.6% +/- 2.4% vs. 92.5% +/- 6.3%, P < 0.001; 29.9 (12.3,
      55.1) mm Hg vs. 52.1(31.5, 76.3) mm Hg, P = 0.014, respectively], D-dimer and NT
      proBNP levels significant reduced (P < 0.001). Mortality rate related to PE was
      6.9% (4/43) and there was no patient developed CTEPH during follow up.
      CONCLUSION: The 100 mg/2 hours rt-PA regimen is effective to treat acute PE
      patients and could improve right heart function and outcome in patients with
      acute PE.

PMID- 23879949
TI  - [Retrospective analysis of patients with thrombocytopenia after patent ductus
      arteriosus interventional occlusion].
AB  - OBJECTIVE: To explore the risk factors of patent ductus arteriosus (PDA) patients
      with thrombocytopenia after PDA interventional occlusion. METHODS:
      Thrombocytopenia occurred in 14 out of 350 patients underwent PDA occlusion. Age,
      gender, body weight, PDA size, occluder size, mean pulmonary arterial pressure,
      the dose of heparin, the manufacturer of occluder, residual shunt after operation
      were analyzed. The recovery time of different grades of thrombocytopenia was
      observed. RESULTS: Multivariate logistic regression showed that the PDA size (OR
      = 2.238, P < 0.05), the dose of heparin (OR = 3.247, P < 0.05), residual shunt
      after operation (OR = 1.912, P < 0.01) were the independent risk factors of
      thrombocytopenia after PDA occlusion. The recovery time of mild thrombocytopenia
      was (7 +/- 2) days without treatment. The recovery time of moderate
      thrombocytopenia was (12 +/- 4) days with glucocorticoids treatment. The recovery
      time of severe thrombocytopenia was (21 +/- 7) days with platelet transfusion.
      CONCLUSIONS: The occluder size, dose of heparin, residual shunt are the
      independent risk factors of thrombocytopenia after PDA interventional occlusion.
      Recover time of thrombocytopenia after PDA interventional occlusion is closely
      related to the severity of thrombocytopenia.

PMID- 23879950
TI  - [Efficacy of catheter radiofrequency ablation for the treatment of ventricular
      arrhythmia storm post cardioverter-defibrillators implantation].
AB  - OBJECTIVE: To evaluate the acute and long-term effects of catheter radiofrequency
      ablation for the treatment of ventricular arrhythmia storm (VAS) post implantable
      cardioverter-defibrillators (ICD) implantation. METHODS: Acute and long-term
      effects of catheter radiofrequency ablation for the treatment of VAS post ICD
      implantation were retrospectively assessed in 11 patients from September 2008 to
      August 2011. RESULTS: A total of 15 ablation procedures were performed in 11
      patients. Six ablation procedures were performed through epicardial approach. In
      9 patients, 20 types of ventricular tachycardia (VT) (including 20%
      hemodynamically unstable VT) were induced during the procedures [mean cycle
      length (384 +/- 141) ms] and polymorphic ventricular tachycardia were induced in
      7 patients. The average X-ray fluoroscopy time and procedural time were (26 +/-
      17) min and (189 +/- 60) min, respectively. Complete success, partial success,
      and failure rates immediately post catheter radiofrequency ablation were 46.7%
      (7/15), 26.7% (4/15) and 26.7% (4/15), respectively. All patients are alive at
      follow-up[(2.45 +/- 9.6) months after the last catheter ablation] and the
      complete success, partial success, and failure rates during follow-up were 72.7%
      (8/11), 9.1% (1/11) and 18.2% (2/11), respectively. CONCLUSION: VAS can be
      effectively treated by catheter radiofrequency ablation in patients post ICD
      implantation.

PMID- 23879951
TI  - [Fasudil reverses monocrotaline-induced pulmonary hypertension in rats].
AB  - OBJECTIVE: To observe the effects and related mechanisms of fasudil on
      monocrotaline-induced pulmonary arterial hypertension (PAH) in rats. METHODS: A
      total of 56 healthy male Sprague-Dawley rats were randomly divided into 5 groups:
      4 weeks control group (N4), 4 weeks PAH group (M4), 8 weeks control group (N8), 8
      weeks PAH group (M8), 8 weeks PAH and fasudil group (F8). PAH was induced by
      subcutaneous injection of monocrotaline (50 mg/kg). Animals in F8 group received
      intraperitoneal injection of fasudil hydrochloride (15 mg*kg(-1)*d(-1)) from the
      end of the 4th week to the end of the 8th week. Rats in control groups and PAH
      groups received equal volume saline injection. Polyethylene catheters were
      inserted into the RV through the jugular vein for right ventricular systolic
      pressure (RVSP) and mean pulmonary artery pressure (mPAP) measurements after
      various treatment protocols. RV hypertrophy index [RV/(LV+S)] was also measured.
      Arteries of 50 to 150 um were evaluated for the median wall thickness and wall
      area by HE staining as follows: percent wall thickness (WT%) = [(medial
      thickness*2/external diameter)]*100 and percent wall area (WA%) = (wall
      area/total area)*100%. The mRNA expression of ROCK-1 in lung tissue was analyzed
      by reverse transcription-polymerase chain reaction (RT-PCR). The protein
      expressions of ROCK-1 and MYPT-1 in lung tissue were analyzed by Western blot and
      MYPT-1 phosphorylation, respectively. RESULTS: Forty-one rats survived and
      mortality rate was zero in N4, N8 and M4 groups. Survival rate was significantly
      higher in F8 group compared to M8 group (75.00% vs. 31.25%, P < 0.05). At the end
      of the 4th week, RVSP [(62.25 +/- 3.24) vs. (31.33 +/- 2.35) mm Hg(1 mm Hg =
      0.133 kPa)], mPAP [(36.38 +/- 2.31) vs.(20.32 +/- 1.81) mm Hg], [RV/(LV+S)]
      (0.5648 +/- 0.0580 vs. 0.3458 +/- 0.0455), WT% [(25.63 +/- 5.35)% vs.(13.38 +/-
      3.45)%], WA% [(60.36 +/- 2.51)% vs. (38.42 +/- 2.84)%] were all significantly
      higher in M4 group than in N4 group (all P < 0.01). RVSP [(54.64 +/- 4.11) vs.
      (67.37 +/- 4.68) mm Hg], mPAP [(26.25 +/- 2.32) vs. (39.83 +/- 1.83) mm Hg], and
      markedly relieve [RV/(LV+S)] (0.3985 +/- 0.0210 vs. 0.7600 +/- 0.0341), WT%
      [(15.64 +/- 2.81)% vs. (28.26 +/- 4.38)%], WA% [(40.35 +/- 2.82)% vs. (68.83 +/-
      1.63)%] were all significantly lower in F8 group than in M8 group (all P < 0.05)
      while the expression of ROCK-1 mRNA (1.2139 +/- 0.1778 vs. 1.6839 +/- 0.3251, P <
      0.01), and the protein expression of ROCK-1 and MYPT-1 as well as the extent of
      MYPT-1 phosphorylation were all downregualted in F8 group compared to M8 group
      (all P < 0.01). CONCLUSIONS: Fasudil can effectively reverse the MCT-induced PAH
      in rats via downregulating ROCK-1 and MYPT-1.

PMID- 23879952
TI  - [Effects of noncoding RNA NRON gene regulation on human umbilical vein
      endothelial cells functions].
AB  - OBJECTIVE: To determine the effects of noncoding repressor of NFAT (NRON)
      overexpression or silencing on human umbilical vein endothelial cells (HUVECs)
      functions. METHODS: Stable HUVECs cell lines with NRON overexpression and short
      hairpin RNA (shRNA) interference were obtained. HUVECs, the empty vector pBABE
      cell line and the empty vector pSuper-cell line served as controls. Cell
      proliferations of these cell lines were tested using MTS method, tube formation
      capacity and migration function were also examined. RESULTS: MTS experiments
      evidenced dose-dependent cells proliferations in all cell lines after 48 h
      culture with fetal bovine serum (HUVECs, r = 0.91;pBABE empty vectors cell-line,
      r = 0.88;NRON overexpression cell-line, r = 0.89;pSuper empty vectors cell-line,
      r = 0.95;shRNA infererence cell-line, r = 0.97). Proliferation capacity was lower
      in NRON overexpressed HUVECs and was higher in NRON silencing HUVECs compared
      with pBABE empty vectors treated and normal HUVECs (all P < 0.05). Tube formation
      and migration functions were also reduced in NRON overexpressed HUVECs [(8.33 +/-
      0.12) roots, (1857 +/- 65) cells] and increased in shRNA infererence of NRON
      treated HUVECs [(36.00 +/- 0.51) roots, (6987 +/- 50) cells] compared with pBABE
      empty vectors treated HUVECs [(19.67 +/- 1.42) roots, (4411 +/- 117) cells],
      pSuper empty vectors treated HUVECs [(17.33 +/- 2.93) roots, (3883 +/- 109)
      cells] and normal HUVECs [(23.33 +/- 3.01) roots, (5145 +/- 72) cells, all P <
      0.05]. CONCLUSION: NRON overexpression could reduce and NRON silencing could
      increase proliferation, tube formation and migration capacities of HUVECs.

PMID- 23879953
TI  - [Control rate of increased low-density lipoprotein cholesterol levels in
      cardiology outpatients with coronary heart disease in Beijing].
AB  - OBJECTIVE: To investigate the low-density lipoprotein cholesterol (LDL-C) levels
      in outpatients with coronary heart disease (CHD) visiting cardiology outpatient
      clinics of 8 hospitals in Beijing. METHODS: A total of 903 outpatients with CHD
      were enrolled from 4 three-tier hospitals and 4 two-tier hospitals in Beijing.
      All patients were asked to finish the questionnaire including demographic data,
      CHD history, the knowledge on cholesterol, and the use of statins. Blood lipid
      was examined and the LDL-C control rate and related factors were then analyzed.
      RESULTS: Questionnaire was obtained from 876 patients [619 male: 70.7%, mean age:
      (64.9 +/- 10.7) years old] and blood lipid data were available in 709 patients.
      The general LDL-C control rate was 36.9% (262/709) and was 13.5% (27/173) in very
      high risk CHD patients, and lower in patients treated in two-tier hospitals than
      patients treated in three-tier hospitals[31.3% (121/386) vs. 43.7% (141/323), P <
      0.01], in female patients than in male patients [27.1% (60/261) vs. 41.3%
      (201/496), P < 0.01] and in diabetic patients than in non-diabetic patients
      [13.5% (27/200) vs. 44.7% (197/441), P < 0.01]. The LDL-C control rate was lower
      in patients less than 60 years old and patients over 80 years old than that in 60
      70 years old patients and 70 - 80 years old patients (P < 0.05). LDL-C control
      rate was not affected by the history of hypertension, percutaneous coronary
      intervention or coronary artery bypass grafting, smoking, lipid examination
      frequency, knowledge on goal level of LDL-C, diet control and regularly physical
      exercising (all P > 0.05). There were 18.2% (129/709) patients not taking statins
      or not aware if they were taking statin or not. The main reason for not taking
      statin [47.9% (23/48)] was statin was no prescribed by doctors, followed by
      withdrawal by patients due to various reasons [27.1% (13/48)]. CONCLUSIONS: LDL-C
      control rate was low in patients with CHD visiting cardiology outpatient clinics
      in Beijing. The CHD patients and cardiologists should be encouraged to achieve
      better LDL-C control by following lipid lowering guidelines and it is also
      important to improve the drug compliance among CHD patients.

PMID- 23879955
TI  - [Progresses in injectable myocardial tissue engineering].

PMID- 23879954
TI  - [Associations of blood pressure level with carotid intima-media thickness and
      plaque among middle-aged and elderly Chinese hypertensives].
AB  - OBJECTIVE: To analyze the associations of blood pressure (BP) level with carotid
      intima-media thickness (CIMT) and plaque in a middle-aged and elderly
      hypertensive population. METHODS: By block randomized sampling, an
      epidemiological investigation was conducted among hypertensives aged 45 - 75
      years in the northern rural area of Jiangsu Province. Blood pressure was
      measured, and carotid CIMT and plaque were determined using a coloured
      ultrasonograph. The relationship between blood pressure level and CIMT or plaque
      was analyzed using a multivariable linear regression or logistic regression
      model. RESULTS: A total of 524 subjects (male 242) were enrolled. CIMT and plaque
      prevalence were (0.7 +/- 0.1) mm and 46.3% in males and (0.7 +/- 0.1) mm and
      34.0% in females. After adjustment for relevant variables, CIMT increased 0.001
      12 mm with 1 mmHg systolic BP increase in males (P < 0.001) but this trend was
      not significant in females. The risk of plaque number > 1 was significantly
      higher in those with grade III hypertension compared to grade I hypertensives
      (OR: 2.136, 95%CI: 1.138 - 4.012, P = 0.018). CONCLUSION: In this middle-aged and
      elderly hypertensive population, carotid CIMT is positively in relation to
      systolic BP, especially for male patients. Higher BP is associated with higher
      risk of plaque occurrence. Hypertension is thus an independent risk factor for
      the formation of atherosclerosis.

PMID- 23879957
TI  - Semantically assessing the reliability of protein interactions.
AB  - Protein-protein interactions (PPIs) play very important roles in many cellular
      processes, and provide rich information for discovering biological facts and
      knowledge. Although various experimental approaches have been developed to
      generate large amounts of PPI data for different organisms, high-throughput
      experimental data usually suffers from high error rates, and as a consequence,
      the biological knowledge discovered from this data is distorted or incorrect.
      Therefore, it is vital to assess the quality of protein interaction data and
      extract reliable protein interactions from the high-throughput experimental data.
      In this paper, we propose a new Semantic Reliability (SR) method to assess the
      reliability of each protein interaction and identify potential false-positive
      protein interactions in a dataset. For each pair of target interacting proteins,
      the SR method takes into account the semantic influence between proteins that
      interact with the target proteins, and the semantic influence between the target
      proteins themselves when assessing the interaction reliability. Evaluations on
      real protein interaction datasets demonstrated that our method outperformed other
      existing methods in terms of extracting more reliable interactions from original
      protein interaction datasets. 

PMID- 23879956
TI  - Linking assumptions in amblyopia.
AB  - Over the last 35 years or so, there has been substantial progress in revealing
      and characterizing the many interesting and sometimes mysterious sensory
      abnormalities that accompany amblyopia. A goal of many of the studies has been to
      try to make the link between the sensory losses and the underlying neural losses,
      resulting in several hypotheses about the site, nature, and cause of amblyopia.
      This article reviews some of these hypotheses, and the assumptions that link the
      sensory losses to specific physiological alterations in the brain. Despite
      intensive study, it turns out to be quite difficult to make a simple linking
      hypothesis, at least at the level of single neurons, and the locus of the sensory
      loss remains elusive. It is now clear that the simplest notion-that reduced
      contrast sensitivity of neurons in cortical area V1 explains the reduction in
      contrast sensitivity-is too simplistic. Considerations of noise, noise
      correlations, pooling, and the weighting of information also play a critically
      important role in making perceptual decisions, and our current models of
      amblyopia do not adequately take these into account. Indeed, although the
      reduction of contrast sensitivity is generally considered to reflect "early"
      neural changes, it seems plausible that it reflects changes at many stages of
      visual processing. 

PMID- 23879958
TI  - LC-MS/MS identification of the O-glycosylation and hydroxylation of amino acid
      residues of collagen alpha-1 (II) chain from bovine cartilage.
AB  - O-Glycosylation of collagen is a unique type of posttranslational modifications
      (PTMs) involving the attachment of galactose (Gal) or glucose-galactose (Glc-Gal)
      moieties to hydroxylysine (HyK). Also, hydroxyproline (HyP) result from the
      posttranslational hydroxylation of some proline residues in collagen. Here, LC
      MS/MS was effectively employed to identify 23 O-glycosylation sites and a large
      number of HyP residues associated with bovine type II collagen alpha-1 chain
      (CO2A1). The modifications of the 23 O-glycosylation sites varied qualitatively
      and quantitatively. Both Gal and Glc-Gal moieties occupied 22 of the identified
      glycosylation sites, while K773 was observed as unmodified. A large number of HyP
      residues at Yaa positions of Gly-Xaa-Yaa motif were detected. HyP residues at Xaa
      positions of Gly-HyP-HyP, Gly-HyP-Ala, and Gly-HyP-Val motifs were also observed.
      Notably, HyP residue of Gly-HyP-Gln motif was detected, which has not been
      previously reported. Moreover, the deamidation of 8 Asn residues was identified,
      of which 2 Asp residues were observed at different retention times because of
      isomerization (Asp vs isoAsp). Partial macroheterogeneities of some CO2A1
      glycosylation sites were revealed by LC-MS/MS analysis. ETD experiments revealed
      partial macroheterogeneities associated with K299-K308, K452-K464, K464-K470, and
      K857-K884 glycosylation sites. Semiquantitative data suggest that the
      glycosylation of hydroxylysine residues is site-specific. 

PMID- 23879959
TI  - Physical and chemical insults induce inflammation and gastrointestinal cancers.
AB  - Chronic inflammation associated with viral and bacterial infections of the
      gastrointestinal tract (GI) and liver renders these organs susceptible to tumour
      development. There is also a growing body of evidence demonstrating that chemical
      and physical insults promote GI cancers by inducing inflammation. For example,
      excessive alcohol consumption and tobacco smoking induces inflammation and
      gastrointestinal carcinogenesis. Likewise, drinking hot beverages and intentional
      or accidental exposure to toxic substances leads to inflammation and GI cancer
      formation. However, further work needs to be undertaken using animal models to
      separate the direct carcinogenic effects of physical and chemical insults from
      the indirect effects of these insults to promote tumor formation through tissue
      inflammation. 

PMID- 23879960
TI  - Inflammatory cytokines in human pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of
      cancer with poor prognosis. Despite extensive efforts, the current treatment
      methods have limited success. Therefore, novel therapeutic approaches are
      required. The pancreatic tumor microenvironment is rich in growth factors and
      inflammatory cytokines that support tumor growth, and it is highly
      immunosuppressive. Up-regulation of cytokine pathways has been shown to modulate
      PDAC progression and immune evasion; therefore targeting cytokines may have
      therapeutic benefits. In this review we provide an overview of current
      understanding of pro- and anti-inflammatory cytokines in pancreatic cancer and
      their potential as therapeutic targets. 

PMID- 23879962
TI  - Enhancement of in vitro cell motility and invasiveness of human malignant pleural
      mesothelioma cells through the HIF-1alpha-MUC1 pathway.
AB  - In this study, we examined the effects of hypoxia on the malignancy of human
      malignant pleural mesothelioma (MPM) cell lines, and found (1) hypoxia enhanced
      motility and invasiveness of human malignant pleural mesothelioma (MPM) cells;
      (2) this phenomenon resulted from increased expression of sialylated MUC1 through
      the activation of HIF-1 pathway; (3) two HIF-binding sites located in the
      promoter region of MUC1 were important for MUC1 transactivation under hypoxia.
      These findings are useful for better understanding molecular mechanisms of
      aggressive behavior of MPM cells and for targeting them in the clinical therapies
      for MPM patients.

PMID- 23879961
TI  - Personalized medicine in CLL: current status and future perspectives.
AB  - Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy in
      the Western Hemisphere. Despite advances in research and the development of
      effective treatment regimens, CLL is still largely an incurable disease. Although
      several prognostic factors have been identified in recent years, most of the new
      prognostic factors are not utilized, and treatment decisions are still based on
      clinical staging and limited use of cytogenetic analysis. Patients with advanced
      disease are treated at diagnosis, whereas others, regardless of their prognostic
      indicators, are offered treatment only at disease progression. Furthermore,
      treatment guidelines for elderly or "unfit" patients are unavailable because most
      CLL trials have included mostly younger, healthier patients. Given
      theheterogeneity of the clinical manifestations and prognosis of CLL, patients
      are likely to benefit from a personalized therapeutic approach. Recent advances
      in CLL pathobiology research, the use of high-throughput technologies, and most
      importantly, the introduction of novel targeted therapies with high efficacy and
      low toxicity are currently transforming the treatment of CLL. A personalized
      approach that includes early intervention in selected patients with CLL is likely
      to bring physicians closer to the goal of attaining cures in most patients with
      CLL. 

PMID- 23879963
TI  - Histone deacetylase 3 participates in self-renewal of liver cancer stem cells
      through histone modification.
AB  - Understanding molecular mechanisms in self-renewal of cancer stem cells (CSCs) is
      important for finding novel target in therapy of cancer. In this study, we
      explored potential effects of histone deacetylase (HDAC) on liver CSCs. Our data
      showed that HDAC inhibitors suppressed self-renewal and induced differentiation
      of liver CSCs. Furthermore, we demonstrated that HDAC3 was selectively expressed
      in liver CSCs and participated in self-renewal of liver CSCs via regulating
      expression of pluripotency factors. Overexpression of HDAC3 was associated with
      poor outcome of liver cancer. HDAC inhibitors could render liver CSCs sensitive
      to sorafenib. Taken together, our data suggest that HDAC3 plays a critical role
      in regulating self-renewal of liver CSCs.

PMID- 23879964
TI  - Next generation analysis of breast cancer genomes for precision medicine.
AB  - For many years breast cancer classification has been based on histology and
      immune-histochemistry. New techniques, more strictly related to cancer biology,
      partially succeeded in fractionating patients, correlated to survival and better
      predicted the patient response to therapy. Nowadays, great expectations arise
      from massive parallel or high throughput next generation sequencing. Cancer
      genomics has already revolutionized our knowledge of breast cancer molecular
      pathology, paving the way to the development of new and more effective clinical
      protocols. This review is focused on the most recent advances in the field of
      cancer genomics and epigenomics, including DNA alterations and driver gene
      mutations, gene fusions, DNA methylation and miRNA expression.

PMID- 23879965
TI  - MiR-487a resensitizes mitoxantrone (MX)-resistant breast cancer cells (MCF-7/MX)
      to MX by targeting breast cancer resistance protein (BCRP/ABCG2).
AB  - Breast cancer resistance protein (BCRP/ABCG2) specifically transports various
      chemotherapeutic agents and is involved in the development of multidrug
      resistance (MDR) in cancer cells. MicroRNAs (miRNAs) can play an important role
      in modulating the sensitivity of cancer cells to chemotherapeutic agents.
      Therefore, after confirming that BCRP was increased in the mitoxantrone (MX)
      resistant MCF-7 breast cancer cell line MCF-7/MX compared with its parental
      sensitive MCF-7 cell line, we aimed to explore the miRNAs that regulate BCRP
      expression and sensitize breast cancer cells to chemotherapeutic agents. In the
      present study, bioinformatic analysis indicated that miR-487a was one of the
      miRNAs that could bind to the 3' untranslated region (3'UTR) of BCRP.
      Quantitative RT-PCR (qRT-PCR) analysis demonstrated that the expression of miR
      487a was reduced in MCF-7/MX cells, and a luciferase reporter assay demonstrated
      that miR-487a directly bound to the 3'UTR of BCRP. Moreover, ectopic miR-487a
      down-regulated BCRP expression at the mRNA and protein levels, increasing the
      intracellular accumulation and cytotoxicity of MX in resistant MCF-7/MX breast
      cancer cells. Meanwhile, inhibition of miR-487a increased BCRP expression at the
      mRNA and protein levels and induced MX resistance in sensitive MCF-7 breast
      cancer cells. Furthermore, the reduced expression of BCRP and increased antitumor
      effects of MX were also detected in MCF-7/MX xenograft tumors treated with the
      miR-487a agmir. Thus, our results suggested that miR-487a can directly regulate
      BCRP expression and reverse chemotherapeutic drug resistance in a subset of
      breast cancers.

PMID- 23879966
TI  - Silibinin reverses drug resistance in human small-cell lung carcinoma cells.
AB  - Small-cell lung carcinoma (SCLC) has a dismal prognosis in part because of
      multidrug resistance (MDR). Silibinin is a flavonolignan extracted from milk
      thistle (Silybum marianum), extracts of which are used in traditional medicine.
      We tested the effects of silibinin on drug-sensitive (H69) and multi-drug
      resistant (VPA17) SCLC cells. VPA17 cells did not show resistance to silibinin
      (IC50 = 60 MUM for H69 and VPA17). Flow cytometry analysis after incubation in 30
      MUM silibinin showed no changes in cell cycle phases in VPA17 or H69 cells
      compared with untreated cells. Silibinin (30 MUM) incubation was pro-apoptotic in
      VPA17 cells after > 3 days, as measured by ELISA of BUdR labeled DNA fragments.
      Apoptosis was also indicated by an increase in caspase-3 specific activity and
      decrease in survivin in VPA17 MDR cells. VPA17 cells had increased Pgp-mediated
      efflux of calcein acetoxymethyl ester (calcein AM); however, this was inhibited
      in cells pre-incubated in silibinin for 5 days. Pre-incubation of VPA17 cells in
      30 MUM silibinin for 5 days also reversed resistance to etoposide (IC50 = 5.50 to
      0.65 MUM) and doxorubicin (IC50 = 0.625 to 0.035 MUM). The possible synergistic
      relationship between silibinin and chemotherapy drugs was determined by exposure
      of VPA17 cells to 1:1 ratios of their respective IC50 values, with serial
      dilutions at 0.25 to 2.0 * IC50 and calculation of the combination index (CI).
      Silibinin and etoposide showed synergism (CI = 0.46 at ED50), as did silibinin
      and doxorubicin (CI = 0.24 at ED50). These data indicate that in SCLC, silibinin
      is pro-apoptotic, reverses MDR and acts synergistically with chemotherapy drugs.
      Silibinin, a non-toxic natural product may be useful in the treatment of drug
      resistant SCLC.

PMID- 23879967
TI  - A novel interaction between calcium-modulating cyclophilin ligand and Basigin
      regulates calcium signaling and matrix metalloproteinase activities in human
      melanoma cells.
AB  - Intracellular free calcium is a ubiquitous second messenger regulating a
      multitude of normal and pathogenic cellular responses, including the development
      of melanoma. Upstream signaling pathways regulating the intracellular free
      calcium concentration ([Ca2+]i) may therefore have a significant impact on
      melanoma growth and metastasis. In this study, we demonstrate that the
      endoplasmic reticulum (ER)-associated protein calcium-modulating cyclophilin
      ligand (CAML) is bound to Basigin, a widely expressed integral plasma membrane
      glycoprotein and extracellular matrix metalloproteinase inducer (EMMPRIN, or
      CD147) implicated in melanoma proliferation, invasiveness, and metastasis. This
      interaction between CAML and Basigin was first identified using yeast two-hybrid
      screening and further confirmed by co-immunoprecipitation. In human A375 melanoma
      cells, CAML and Basigin were co-localized to the ER. Knockdown of Basigin in
      melanoma cells by siRNA significantly decreased resting [Ca2+]i and the [Ca2+]i
      increase induced by the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA)
      inhibitor thapsigargin (TG), indicating that the interaction between CAML and
      Basigin regulates ER-dependent [Ca2+]i signaling. Meanwhile upregulating the
      [Ca2+]i either by TG or phorbol myristate acetate (PMA) could stimulate the
      production of MMP-9 in A375 cells with the expression of Basigin. Our study has
      revealed a previously uncharacterized [Ca2+]i signaling pathway that may control
      melanoma invasion, and metastasis. Disruption of this pathway may be a novel
      therapeutic strategy for melanoma treatment.

PMID- 23879968
TI  - Synergistic effect of combined treatment with gamma-tocotrienol and statin on
      human malignant mesothelioma cells.
AB  - The present study is the first to demonstrate the synergetic effect of statins
      (atorvastatin and simvastatin) and gamma-tocotrienol (gamma-T3) on human
      malignant mesothelioma (MM). Statin + gamma-T3 combinations induced greater cell
      growth inhibition more than each single treatment via inhibition of mevalonate
      pathway, a well-known target of both gamma-T3 and statins. gamma-T3 was necessary
      for endoplasmic reticulum stress markers CHOP and GRP78, whereas an intrinsic
      apoptotic marker, caspase 3 activation was induced only in the presence of
      statins. Overall, the combination of gamma-T3 and statins could be useful for MM
      therapy and functions in a complementary style.

PMID- 23879969
TI  - Autophagy contributes to the survival of CD133+ liver cancer stem cells in the
      hypoxic and nutrient-deprived tumor microenvironment.
AB  - Liver cancer stem cells (LCSCs) can drive and maintain hepatocellular carcinoma
      (HCC) growth, metastasis, and recurrence. Therefore, they are potentially
      responsible for the poor prognosis of HCC. Oxygen and nutrient deficiencies are
      common characteristics of the tumor microenvironment. However, how LCSCs adapt to
      oxygen- and nutrient-deprived conditions is unclear. Here, we used
      immunofluorescent staining and flow cytometry analysis to show that CD133+ cells
      were significantly enriched after hypoxia and nutrient starvation (H/S) in the
      human HCC cell line Huh7. Sorted CD133+ cells showed higher survival, less
      apoptosis, and possess higher clonogenic ability under H/S compared to the CD133-
      population. Under H/S, electron microscopy revealed more advanced autophagic
      vesicles in CD133+ cells. Additionally, CD133+ cells had higher autophagy levels
      as measured by both RT-qPCR and Western blotting. CD133+ cells had more
      accumulated GFP-LC3 puncta, which can be detected by fluorescence microscopy. The
      autophagic inhibitor chloroquine (CQ) significantly increased apoptosis and
      decreased the clonogenic capacity of CD133+ cells under H/S. Pre-culturing in H/S
      enhanced the sphere-forming capacity of CD133+ cells. However, CQ significantly
      impaired this process. Therefore, autophagy is essential for LCSCs maintenance.
      CD133+ cells were also found to have a higher tumor-forming ability in vivo,
      which could be inhibited by CQ administration. Collectively, our results indicate
      that the involvement of autophagy in maintenance of CD133+ LCSCs under the oxygen
      and nutrient-deprived conditions that are typical of the tumor microenvironment
      in HCC. Therefore, autophagy inhibitors may make LCSCs more sensitive to the
      tumor microenvironment and be useful in improving anti-cancer treatments.

PMID- 23879970
TI  - Association of an impaired bone marrow microenvironment with secondary poor graft
      function after allogeneic hematopoietic stem cell transplantation.
AB  - Poor graft function (PGF) is a serious complication after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). Whether abnormalities of the
      bone marrow (BM) microenvironment are involved in the pathogenesis of PGF is
      unclear. In the present prospective nested case-control study, 19 patients with
      secondary PGF, 38 matched patients with good graft function (GGF) after allo
      HSCT, and 15 healthy donors (HDs) were enrolled. The cellular elements of the BM
      microenvironment, including endosteal cells, perivascular cells, and vascular
      cells, were analyzed by flow cytometry as well as hematoxylin and eosin and
      immunohistochemical staining in situ. The median time to occurrence of secondary
      PGF was 90 days post-transplantation (range, 58 to 264 days). The patients with
      PGF showed markedly hypocellular marrow (10% versus 45% versus 45%; P < .0001)
      with scattered hematopoietic cells and significantly lower CD34(+) cells (0.07%
      versus 0.26% versus 0.26%; P < .0001), endosteal cells (4 per high-power field
      [hpf] versus 16 per hpf versus 20 per hpf; P < .001), perivascular cells (0.008%
      versus 0.10% versus 0.12%; P < .0001), and endothelial progenitor cells (0.008%
      versus 0.16% versus 0.18%; P < .0001) compared with GGF allo-HSCT recipients and
      HDs, respectively. Multivariate analyses revealed that endothelial progenitor
      cells (odds ratio, 150.72; P = .001) and the underlying disease (odds ratio,
      18.52; P = .007) were independent risk factors for secondary PGF. Our results
      suggest that the impaired BM microenvironment may contribute to the occurrence of
      secondary PGF post-HSCT.

PMID- 23879974
TI  - Polycomblike protein PHF1b: a transcriptional sensor for GABA receptor activity.
AB  - BACKGROUND: The gamma-aminobutyric acid (GABA) type A receptor (GABA(A)R)
      contains the recognition sites for a variety of agents used in the treatment of
      brain disorders, including anxiety and epilepsy. A better understanding of how
      receptor expression is regulated in individual neurons may provide novel
      opportunities for therapeutic intervention. Towards this goal we have studied
      transcription of a GABA(A)R subunit gene (GABRB1) whose activity is autologously
      regulated by GABA via a 10 base pair initiator-like element (beta(1)-INR).
      METHODS: By screening a human cDNA brain library with a yeast one-hybrid assay,
      the Polycomblike (PCL) gene product PHD finger protein transcript b (PHF1b) was
      identified as a beta(1)-INR associated protein. Promoter/reporter assays in
      primary rat cortical cells demonstrate that PHF1b is an activator at GABRB1, and
      chromatin immunoprecipitation assays reveal that presence of PHF1 at endogenous
      Gabrb1 is regulated by GABA(A)R activation. RESULTS: PCL is a member of the
      Polycomb group required for correct spatial expression of homeotic genes in
      Drosophila. We now show that PHF1b recognition of beta(1)-INR is dependent on a
      plant homeodomain, an adjacent helix-loop-helix, and short glycine rich motif. In
      neurons, it co-immunoprecipitates with SUZ12, a key component of the Polycomb
      Repressive Complex 2 (PRC2) that regulates a number of important cellular
      processes, including gene silencing via histone H3 lysine 27 trimethylation
      (H3K27me3). CONCLUSIONS: The observation that chronic exposure to GABA reduces
      PHF1 binding and H3K27 monomethylation, which is associated with transcriptional
      activation, strongly suggests that PHF1b may be a molecular transducer of
      GABA(A)R function and thus GABA-mediated neurotransmission in the central nervous
      system.

PMID- 23879977
TI  - [Latest evidence about longevity of Sun Simiao].
AB  - Recording in the preface of Binglishufu (written by Lu Zhaolin of the Tang
      Dynasty) was the only direct evidence about the longevity of Sun Simiao. It
      recorded 'Sun Simiao said since his birth in the Xinyou Year of the Kaihuang
      Period, he was 93 years old'. But there were disputes over the time of Xinyou
      Year-581 AD or 541 AD? It is easy to pick holes in both arguments and the whole
      research, so the conclusion is not reliable. Recordings in Biography of Sun
      Simiao, which said 'the governor of the Luozhou area marveled at Sun's
      intelligence and called him the saint child', are also fabricated. According to
      literature, 'in the 3(rd) year of the Xianqing Period, Sun Simiao was invited by
      the emperor and lived in the deserted house of the Boyang Princess. He was more
      than 90 years old and did not have any visual or hearing loss ... he was good to
      give lectures at various schools like Zhuang and Lao ... in the Zhou Xuan Emperor
      Period Sun was tired of royal affairs and chose to be a hermit in the Taibai
      Mountain' (Tanghuiyao, Datang Xinyu, Tanbinlu). Sun Simiao should have been born
      in 560 AD. This time conformed to the time of his other events. He was 20 when a
      hermit and was 99 when he was invited by the Emperor Gaozong in the 3(rd) year of
      Xianqing. 

PMID- 23879975
TI  - Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell
      lines and expression is differentially regulated in vitro by ghrelin.
AB  - BACKGROUND: Ghrelin is a 28 amino acid peptide hormone that is expressed in the
      stomach and a range of peripheral tissues, where it frequently acts as an
      autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation
      required for it to activate its cognate receptor, the growth hormone secretagogue
      receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the
      enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the
      third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified.
      METHODS: We used cell culture, quantitative real-time reverse transcription (RT)
      PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate
      cancer cell lines and tissues from patients. Real-time RT-PCR was used to
      demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in
      prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin
      and desacyl ghrelin and the effect on GOAT expression was measured using
      quantitative RT-PCR. RESULTS: We have demonstrated that GOAT mRNA and protein are
      expressed in the normal prostate and human prostate cancer tissue samples. The
      RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and
      PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is
      necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or
      furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can
      directly regulate the expression of GOAT in the RWPE-1 normal prostate derived
      cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6
      hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3
      prostate cancer cell line, however, ghrelin did not regulate GOAT expression in
      the DU145 and LNCaP prostate cancer cell lines. CONCLUSIONS: This study
      demonstrates that GOAT is expressed in prostate cancer specimens and cell lines.
      Ghrelin regulates GOAT expression, however, this is likely to be cell-type
      specific. The expression of GOAT in prostate cancer supports the hypothesis that
      the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1
      prostate cell line and the PC3 prostate cancer cell line may be useful for
      investigating GOAT regulation and function.

PMID- 23879976
TI  - Sustainable rare diseases business and drug access: no time for misconceptions.
AB  - Legislative incentives enacted in Europe through the Regulation (EC) No. 141/2000
      to incentivize orphan drug development have over the last 12 years constituted a
      powerful impetus toward R&D directed at the rare diseases population. However,
      despite therapeutic promises contained in these projects and significant economic
      impact linked to burgeoning R&D expenditures, the affordability and value of OMPs
      has become a topic of health policy debate in Europe fueled by the perception
      that OMPs have high acquisition costs, and by misconceptions around pricing
      dynamics and rare-diseases business models. In order to maintain sustainable
      patient access to new and innovative therapies, it is essential to address these
      misconceptions, and to ensure the successful continuation of a dynamic OMPs R&D
      within rare-diseases public health policy. Misconceptions abound regarding the
      pricing of rare diseases drugs and reflect a poor appreciation of the R&D model
      and the affordability and value of OMPs. Simulation of potential financial
      returns of small medium sized rare diseases companies focusing on high priced
      drugs show that their economic returns are likely to be close to their cost of
      capital. Research in rare diseases is a challenging endeavour characterised by
      high fixed costs in which companies accrue substantial costs for several years
      before potentially generating returns from the fruits of their investments.
      Although heavily dependent upon R&D capabilities of each individual company or
      R&D organization, continuous flow of R&D financial investment should allow
      industry to increasingly include efficiencies in research and development in cost
      considerations to its customers. Industry should also pro-actively work on
      facilitating development of a specific value based pricing approach to help
      understanding what constitute value in rare diseases. Policy makers must reward
      innovation based upon unmet need and patient outcome. Broader understanding by
      clinicians, the public, and policy makers of the complexity of clinical programs
      to deliver OMPs to market is required to better comprehend the decisions needed
      and made by industry. In parallel, an overt effort to consider the impact of
      public policies on R&D investments is key to enable policy makers to better
      reconcile the incentives provided by public policy decisions and companies
      investments decisions in a more positive manner.

PMID- 23879978
TI  - [Methods of eliminating putrefaction in TCM surgery].
AB  - Eliminating putrefaction is a characteristic therapy in TCM surgery. It is more
      inclusive, reliable and safer nowadays after development for thousands of years.
      From the 20(th) century, with the development of science and technology, personal
      injury resulting from heavy metals has drawn more and more attention. Many drugs
      with heavy metal ingredients such as arsenic, mercury and lead were forbidden in
      clinical practice. This therapy had played an important role in Chinese medical
      history and it should not be abandoned as refraining from treatment with a
      necessary method for fear of a slight risk. With a long history, various methods
      of eliminating putrefaction have been developed by doctors, especially doctors in
      Ming and Qing Dynasties. The thoughts and experience of those doctors are still
      well worth learning and researching. 

PMID- 23879979
TI  - [Anatomy of pi in TCM].
AB  - Description about pi's (spleen) morphology, size, color and weight in Neijing and
      Nanjing conformed to that in anatomy. Most Chinese doctors inherited this opinion
      and it was also the mainstream viewpoint in TCM. While pi described by the famous
      doctor Wang Qingren actually was the pancreatic gland, which was not accepted by
      later generations. Zhang Shouyi, a doctor in modern times, thought pi in TCM
      should include the spleen and the pancreatic gland. This viewpoint was quoted and
      identified by many people, but it couldn't be right according to anatomy and
      research by the ancients. In TCM, people got anatomic knowledge in practice and
      pi should refer to the spleen in modern anatomy. 

PMID- 23879980
TI  - [Formation and differentiation of the famous coptis regions].
AB  - From the Tang Dynasty, Xuanzhou has been considered as the famous area of genuine
      regional coptis as its production of high-quality. Till the Ming Dynasty, coptis
      resource in Xuanzhou was exhausted, and weilian, yalian (coptis produced in two
      districts in Sichuan) and yunlian (coptis produced in Yunnan) became famous
      region coptis, three varieties of coptis coming from three districts. During the
      formation of new famous regions, species variation, geographical environment,
      historical background, cultivation technique and social economy played a role.
      For example, xuanlian became famous for doctors in Xinan area loved to use it to
      a large extent. And cultivation technique was the key point for weilian to become
      the famous-region herb. Now with the shrinking of planting area, yalian could be
      hardly considered as famous-region copitis and yunlian has withdrawn from
      commodity for its high cost and low production. 

PMID- 23879981
TI  - [Compilation of Yan ke zheng zong yuan ji qi wei (Orthodox Ophthalmology:
      Revealing the Mystery of Eye Disease) and its academic achievements].
AB  - As an ophthalmic monograph compiled to systemize and elaborate the Yuan ji qi wei
      (Revealing the Mystery of Eye Disease) written to explore the gist of the
      original author, a valuable edition of the original Yuan ji qi wei. SHI Shi-de
      made reviews and comments to each eye disease included in the first volume of
      Yuan ji qi wei, followed by the rhymes on the etiology, manifestations, treatment
      and prescriptions written by his son SHI Guang, and rearranged and systemized the
      whole text made by his little brother SHI Shi-qi for better memory and
      popularization. He stressed the significant position of Yuan ji qi wei. The
      achievements of the Yan ke zheng zong yuan ji qi wei can be summarized into 4
      points: the "18 disease" of eye disease is the guidelines for the differential
      diagnosis of ophthalmic diseases; Shi's annotation developed the essence of Ni's
      theory; SHI Guang's rhymes facilitated the spread of Ni's theory; the "hints for
      prescription" being the standards for the treatment of eye disease. 

PMID- 23879982
TI  - [Medical statistics in the late Qing dynasty].
AB  - Chinese medical statistics basically went through three stages in the Late Qing
      Dynasty. The early stage was individual behavior of missionary doctors. In the
      early 16(th) century, western countries began to collect materials about medicine
      and public health in China. After the Opium War in 1840, more missionaries came
      to China and more doctors engaged in medical information collection and
      statistics. In 1860s, the western countries stole the customs power control from
      the Qing's government and the systematization process of statistics began. The
      process, content, method and time of statistics were improved. In the 20(th)
      century, modernity of medicine became the scale for a country's self-management
      qualification. Statistics was needed by the Qing government and relevant medical
      administration was established. During this process, they carried out this
      activity with different purposes according to the different participants. But
      from the point of influence, medical statistics promoted the spread and
      development of western medicine in China. They were also helpful to the
      perfection of medical research and public health system in China. 

PMID- 23879983
TI  - [Development of Western Hospitals in Shanghai in modern times-study of hospitals
      affiliated to the Municipal Council].
AB  - The first western hospital, Renji Hospital, was set up in Shanghai in 1844. Until
      1943, 72 western hospitals were founded in public concession and among them 14
      were affiliated to the Municipal Council. The establishment of Municipal Council
      affiliated hospitals marked the beginning of the Municipal Council offering
      service to the public. Apart from of Municipal Council affiliated hospitals,
      there were also western hospitals in the public concession created by social
      societies or individuals. The appearance of western hospitals promoted the change
      of object where people sought medical service, and embodied people's increased
      need of western medicine, which promoted the systemization of western medicine in
      China to some extent. 

PMID- 23879984
TI  - [On two editions of Yunyu Xuanji and their source].
AB  - Yunyu Xuanji is considered as one of the 400 key ancient books in the 'TCM
      Ancient Books Protection and Use Project' by the State Bureau of TCM. Two
      editions of this book are hand-written copies. The Qianyao edition was finished
      in the 52(nd) year of the Kangxi Period (1713). The other edition (Taoshi
      Xianyishukoucongshu) was probably done in the Late Qing Dynasty or the period of
      the Republic of China. By careful comparison, the contents of the two editions
      are basically the same, and only the preface of the former edition has been given
      some changes, which were probably made by later generations. The second
      manuscript was written in a more standard mode. Therefore the two editions were
      written according to the same literature and it is possible that the latter one
      is the copied edition of the Qianyao edition. 

PMID- 23879985
TI  - [Author and time of writing of Shanghanlun Jujie].
AB  - Li Wenjin (courtesy name of Xiangyi, the styled names as Zhian and Shujingtang
      Zhuren), lived in Xu Village, south of Tianyin Mountain, Jinling. He was born on
      the 47(th) year of the Kangxi Period (1708) and died approximately at the end of
      the Qianlong Period. Bold and generous, he liked making friends and practising
      medicine, divination, astrology, and also writing poetry and painting. Later he
      devoted himself to medicine and wrote Shanghanlun Jujie and Yijia 24 ze.
      Shanghanlun Jujie included Shanghanzabinglun Shujingtangqinjie (14 volumes) and
      Siwenji (7 volumes). The former one was written in 1768 and was his annotation of
      Shanghanlun. Siwenji included Shujingtang Gaidingzhushi Hanrewenpingyaoxingfu (4
      volumes), Shujingtang Shenyizazhu (1 volume), Yiyao Zhenyan (1 volume) and
      Shujingtang Yiyaojian (1 volume) and was finished in 1765. 

PMID- 23879986
TI  - Infant color vision and color preferences: a tribute to Davida Teller.
AB  - Almost 40 years ago, Davida Teller developed the forced-choice preferential
      looking method for studying infant visual capabilities and used it to study
      infant color vision. About 10 years ago, she used infant looking preferences to
      study infant color perception. Here, we examine four data sets in which the
      infant looking preference was measured using a wide range of saturated colors.
      Three of those data sets, from papers by Marc Bornstein and by Davida Teller and
      Anna Franklin and their respective collaborators, were fit successfully using
      MacLeod and Boynton's model of the equiluminant plane in color space, in spite of
      the varied luminances used in those studies. A fourth data set, from a paper by
      Zemach, Chang, and Teller, was less well fit by that model. Apparently, infants
      are able to ignore luminance, and pay attention just to the color of stimuli.
      These results are discussed in the context of Davida Teller's work on the
      philosophy of vision science. 

PMID- 23879987
TI  - A computational pipeline for quantification of pulmonary infections in small
      animal models using serial PET-CT imaging.
AB  - BACKGROUND: Infectious diseases are the second leading cause of death worldwide.
      In order to better understand and treat them, an accurate evaluation using multi
      modal imaging techniques for anatomical and functional characterizations is
      needed. For non-invasive imaging techniques such as computed tomography (CT),
      magnetic resonance imaging (MRI), and positron emission tomography (PET), there
      have been many engineering improvements that have significantly enhanced the
      resolution and contrast of the images, but there are still insufficient
      computational algorithms available for researchers to use when accurately
      quantifying imaging data from anatomical structures and functional biological
      processes. Since the development of such tools may potentially translate basic
      research into the clinic, this study focuses on the development of a quantitative
      and qualitative image analysis platform that provides a computational radiology
      perspective for pulmonary infections in small animal models. Specifically, we
      designed (a) a fast and robust automated and semi-automated image analysis
      platform and a quantification tool that can facilitate accurate diagnostic
      measurements of pulmonary lesions as well as volumetric measurements of
      anatomical structures, and incorporated (b) an image registration pipeline to our
      proposed framework for volumetric comparison of serial scans. This is an
      important investigational tool for small animal infectious disease models that
      can help advance researchers' understanding of infectious diseases. METHODS: We
      tested the utility of our proposed methodology by using sequentially acquired CT
      and PET images of rabbit, ferret, and mouse models with respiratory infections of
      Mycobacterium tuberculosis (TB), H1N1 flu virus, and an aerosolized respiratory
      pathogen (necrotic TB) for a total of 92, 44, and 24 scans for the respective
      studies with half of the scans from CT and the other half from PET. Institutional
      Administrative Panel on Laboratory Animal Care approvals were obtained prior to
      conducting this research. First, the proposed computational framework registered
      PET and CT images to provide spatial correspondences between images. Second, the
      lungs from the CT scans were segmented using an interactive region growing (IRG)
      segmentation algorithm with mathematical morphology operations to avoid false
      positive (FP) uptake in PET images. Finally, we segmented significant radiotracer
      uptake from the PET images in lung regions determined from CT and computed
      metabolic volumes of the significant uptake. All segmentation processes were
      compared with expert radiologists' delineations (ground truths). Metabolic and
      gross volume of lesions were automatically computed with the segmentation
      processes using PET and CT images, and percentage changes in those volumes over
      time were calculated. (Continued on next page)(Continued from previous page)
      Standardized uptake value (SUV) analysis from PET images was conducted as a
      complementary quantitative metric for disease severity assessment. Thus, severity
      and extent of pulmonary lesions were examined through both PET and CT images
      using the aforementioned quantification metrics outputted from the proposed
      framework. RESULTS: Each animal study was evaluated within the same subject
      class, and all steps of the proposed methodology were evaluated separately. We
      quantified the accuracy of the proposed algorithm with respect to the state-of
      the-art segmentation algorithms. For evaluation of the segmentation results, dice
      similarity coefficient (DSC) as an overlap measure and Haussdorf distance as a
      shape dissimilarity measure were used. Significant correlations regarding the
      estimated lesion volumes were obtained both in CT and PET images with respect to
      the ground truths (R2=0.8922,p<0.01 and R2=0.8664,p<0.01, respectively). The
      segmentation accuracy (DSC (%)) was 93.4+/-4.5% for normal lung CT scans and
      86.0+/-7.1% for pathological lung CT scans. Experiments showed excellent
      agreements (all above 85%) with expert evaluations for both structural and
      functional imaging modalities. Apart from quantitative analysis of each animal,
      we also qualitatively showed how metabolic volumes were changing over time by
      examining serial PET/CT scans. Evaluation of the registration processes was based
      on precisely defined anatomical landmark points by expert clinicians. An average
      of 2.66, 3.93, and 2.52 mm errors was found in rabbit, ferret, and mouse data
      (all within the resolution limits), respectively. Quantitative results obtained
      from the proposed methodology were visually related to the progress and severity
      of the pulmonary infections as verified by the participating radiologists.
      Moreover, we demonstrated that lesions due to the infections were metabolically
      active and appeared multi-focal in nature, and we observed similar patterns in
      the CT images as well. Consolidation and ground glass opacity were the main
      abnormal imaging patterns and consistently appeared in all CT images. We also
      found that the gross and metabolic lesion volume percentage follow the same trend
      as the SUV-based evaluation in the longitudinal analysis. CONCLUSIONS: We
      explored the feasibility of using PET and CT imaging modalities in three distinct
      small animal models for two diverse pulmonary infections. We concluded from the
      clinical findings, derived from the proposed computational pipeline, that PET-CT
      imaging is an invaluable hybrid modality for tracking pulmonary infections
      longitudinally in small animals and has great potential to become routinely used
      in clinics. Our proposed methodology showed that automated computed-aided lesion
      detection and quantification of pulmonary infections in small animal models are
      efficient and accurate as compared to the clinical standard of manual and semi
      automated approaches. Automated analysis of images in pre-clinical applications
      can increase the efficiency and quality of pre-clinical findings that ultimately
      inform downstream experimental design in human clinical studies; this innovation
      will allow researchers and clinicians to more effectively allocate study
      resources with respect to research demands without compromising accuracy.

PMID- 23879988
TI  - Understanding breast cancer stem cell heterogeneity: time to move on to a new
      research paradigm.
AB  - Human breast cancer (BC) is one of the leading causes of death for women
      worldwide, and is characterized by a group of highly heterogeneous lesions. The
      morphological and biomolecular heterogeneity of BC cells, accompanied by dynamic
      plasticity of the BC microenvironment and the presence of stem-like cells, make
      tumor categorization an urgent and demanding task.The major limitations in BC
      research include the high flexibility rate of breast cancer stem cells (BCSCs)
      and the difficulty of their identification. Improved profiling methods and
      extensive characterization of BCSCs were recently presented in BMC Cancer,
      highlighting that the majority of BC cells had a luminal EpCAMhigh/CD49f+
      phenotype, and identification of CD44high/CD24low subpopulation of cancer stem
      cells significantly improves the flow cytometry measurement of BCSCs with higher
      stem/progenitor ability.Future developments in single-cell omics will potentially
      revolutionize cancer biology and clinical practice, providing better
      understanding of BC heterogeneity, how BCSCs evolve, and which BC cells to target
      to avoid drug resistance.Please see related research published in BMC Cancer:
      http://www.biomedcentral.com/1471-2407/13/289/abstract. 

PMID- 23879990
TI  - Linking perception to neural activity as measured by visual evoked potentials.
AB  - Linking propositions have played an important role in refining our understanding
      of the relationship between neural activity and perception. Over the last 40
      years, visual evoked potentials (VEPs) have been used in many different ways to
      address questions of the relationship between neural activity and perception.
      This review organizes and discusses this research within the linking proposition
      framework developed by Davida Teller, and her colleagues. A series of examples
      from the VEP literature illustrates each of the five classes of linking
      propositions originally proposed by Davida Teller. The related concept of the
      bridge locus-the site at which neural activity can be said to first be
      proscriptive of perception-is discussed and a suggestion is made that the concept
      be expanded to include an evolution over time and cortical area. 

PMID- 23879989
TI  - Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic
      anomalies - expanding the phenotypes associated with EFTUD2 mutations.
AB  - BACKGROUND: Mutations in EFTUD2 were proven to cause a very distinct
      mandibulofacial dysostosis type Guion-Almeida (MFDGA, OMIM #610536). Recently,
      gross deletions and mutations in EFTUD2 were determined to cause syndromic
      esophageal atresia (EA), as well. We set forth to find further conditions caused
      by mutations in the EFTUD2 gene (OMIM *603892). METHODS AND RESULTS: We performed
      exome sequencing in two familial cases with clinical features overlapping with
      MFDGA and EA, but which were previously assumed to represent distinct entities, a
      syndrome with esophageal atresia, hypoplasia of zygomatic complex, microcephaly,
      cup-shaped ears, congenital heart defect, and intellectual disability in a mother
      and her two children [AJMG 143A(11):1135-1142, 2007] and a supposedly autosomal
      recessive oto-facial syndrome with midline malformations in two sisters [AJMG
      132(4):398-401, 2005]. While the analysis of our exome data was in progress, a
      recent publication made EFTUD2 mutations highly likely in these families. This
      hypothesis could be confirmed with exome as well as with Sanger sequencing. Also,
      in three further sporadic patients, clinically overlapping to these two families,
      de novo mutations within EFTUD2 were identified by Sanger sequencing. Our
      clinical and molecular workup of the patients discloses a broad phenotypic
      spectrum, and describes for the first time an instance of germline mosaicism for
      an EFTUD2 mutation. CONCLUSIONS: The clinical features of the eight patients
      described here further broaden the phenotypic spectrum caused by EFTUD2 mutations
      or deletions. We here show, that it not only includes mandibulofacial dysostosis
      type Guion-Almeida, which should be reclassified as an acrofacial dysostosis
      because of thumb anomalies (present in 12/35 or 34% of patients) and syndromic
      esophageal atresia [JMG 49(12). 737-746, 2012], but also the two new syndromes,
      namely oto-facial syndrome with midline malformations published by Megarbane et
      al. [AJMG 132(4): 398-401, 2005] and the syndrome published by Wieczorek et al.
      [AJMG 143A(11): 1135-1142, 2007] The finding of mild phenotypic features in the
      mother of one family that could have been overlooked and the possibility of
      germline mosaicism in apparently healthy parents in the other family should be
      taken into account when counseling such families.

PMID- 23879991
TI  - Drug combination improves outcomes after in hospital cardiac arrest.

PMID- 23879993
TI  - [Standardized diagnosis and treatment of osteosarcoma in China is imperative].

PMID- 23879992
TI  - Development of a screen to identify selective small molecules active against
      patient-derived metastatic and chemoresistant breast cancer cells.
AB  - INTRODUCTION: High failure rates of new investigational drugs have impaired the
      development of breast cancer therapies. One challenge is that excellent activity
      in preclinical models, such as established cancer cell lines, does not always
      translate into improved clinical outcomes for patients. New preclinical models,
      which better replicate clinically-relevant attributes of cancer, such as
      chemoresistance, metastasis and cellular heterogeneity, may identify novel anti
      cancer mechanisms and increase the success of drug development. METHODS:
      Metastatic breast cancer cells were obtained from pleural effusions of consented
      patients whose disease had progressed. Normal primary human breast cells were
      collected from a reduction mammoplasty and immortalized with human telomerase.
      The patient-derived cells were characterized to determine their cellular
      heterogeneity and proliferation rate by flow cytometry, while dose response
      curves were performed for chemotherapies to assess resistance. A screen was
      developed to measure the differential activity of small molecules on the growth
      and survival of patient-derived normal breast and metastatic, chemoresistant
      tumor cells to identify selective anti-cancer compounds. Several hits were
      identified and validated in dose response assays. One compound, C-6, was further
      characterized for its effect on cell cycle and cell death in cancer cells.
      RESULTS: Patient-derived cells were found to be more heterogeneous, with reduced
      proliferation rates and enhanced resistance to chemotherapy compared to
      established cell lines. A screen was subsequently developed that utilized both
      tumor and normal patient-derived cells. Several compounds were identified, which
      selectively targeted tumor cells, but not normal cells. Compound C-6 was found to
      inhibit proliferation and induce cell death in tumor cells via a caspase
      independent mechanism. CONCLUSIONS: Short-term culture of patient-derived cells
      retained more clinically relevant features of breast cancer compared to
      established cell lines. The low proliferation rate and chemoresistance make
      patient-derived cells an excellent tool in preclinical drug development.

PMID- 23879994
TI  - [Morphological observation of human gastric cancer cell SGC-7901 clones and
      identification of gastric cancer stem cells].
AB  - OBJECTIVE: To dynamically investigate the morphology of human gastric cancer SGC
      7901 cell clones, and then compare the tumorigenic ability of different clones in
      order to identify the tumor stem cell clones. METHODS: Clones derived from
      gastric cancer SGC-7901 cells were assessed by morphological observation, and the
      clone formation rate and proportion of each clone were calculated. The expression
      of CD44 and CDX2 in different clones was detected by immunofluorescence
      microscopy and Western blot. Furthermore, different clones were isolated and
      cultured, and their self-renewal property was assayed. Cells of different clones
      were subcutaneously inoculated into nude mice and the tumorigenic ability of each
      group was determined. RESULTS: Clones derived from gastric cancer SGC-7901 cells
      had three types, i.e. clones of tight, transitional and loose types. The total
      clone formation rate was (9.80 +/- 1.07)%, and the proportion of tight,
      transitional and loose type clones was 10.2%, 56.0% and 33.8%, respectively. The
      results of immunofluorescence microscopic examination showed that the signal of
      CD44 was significantly stronger in the tight clones than in the transitional and
      loose clones, however, the signal of CDX2 was weakest in the tight colonies. The
      results of Western blot were consistent with that of immunofluorescence
      microscopic observation. SGC-7901 cells of tight clones possessed strong ability
      of self-renewal and in vivo tumorigenicity in the nude mice. CONCLUSION: SGC-7901
      cell clones vary in morphology and differentiation, and the tight type clones may
      include rich gastric cancer stem cells.

PMID- 23879995
TI  - [ZNF217 expression correlates with the biological behavior of human ovarian
      cancer cells].
AB  - OBJECTIVE: To investigate the correlation of ZNF217 gene expression with the
      biological behavior of human ovarian cancer HO-8910 cells. METHODS: The
      expression of ZNF217 in ovarian carcinoma cell lines was detected by RT-PCR and
      Western blot, respectively. The biological behaviors of the transfectants were
      investigated by MTT, in vitro Boyden chamber and in vivo invasion assay,
      respectively. RESULTS: RT-PCR and Western blotting revealed that transfection of
      ZNF217 into the HO-8910 cells significantly increased their proliferation along
      with markedly enhanced in vitro and in vivo invasion and metastatic abilities.
      MTT assay showed that the proliferation ability of pEGFP-N1-ZNF217/HO-8910 cells
      was significantly higher than that of pEGFP-N1/HO-8910 cells and HO-8910 cells (P
      < 0.001). The Boyden chamber assay showed that the numbers of migrating pEGFP-N1
      ZNF217/HO-8910, pEGFP-N1/HO-8910 and HO-8910 cells were (141.25 +/- 13.91)
      cells/200*field, (82.50 +/- 11.73) cells/200*field and (81.75 +/-
      12.12)cells/200*field, with a significant difference between them (F = 29.247, P
      < 0.001). The nude mouse experiment showed that the in vivo tumor formation
      ability of pEGFP-N1-ZNF217/HO-8910 cells was significantly higher than that of
      pEGFP-N1/HO-8910 cells (P < 0.001). CONCLUSIONS: ZNF217 gene plays an important
      role in the invasion and metastasis of ovarian cancer. ZNF217 gene expression may
      be a useful marker indicating invasion and metastasis of ovarian cancer.

PMID- 23879996
TI  - [Inhibitory effect and significance of rapamycin on the mammalian target of
      rapamycin signaling pathway in osteosarcoma stem cells and osteosarcoma cells].
AB  - OBJECTIVE: To observe the effect of rapamycin on the MG-63 osteosarcoma cells
      (OC), osteosarcoma stem cells (OSC) and on mTOR signaling pathway, and explore
      the feasibility of rapamycin as a novel therapeutic measure in osteosarcoma
      chemotherapy regimens. METHODS: OC and OSC were cultured in vitro.
      Immunofluorescence assay was used to detect the expression of Nanog and Oct4 in
      OC and OSC. OC and OSC were treated with rapamycin in concentrations of 0, 20, 50
      and 100 nmol/L. Semi-quantitative PCR and RT-PCR were used to detect the mTOR
      mRNA and CCK-8 assay was used to detect cell proliferation, and the cell
      morphology was observed under an inverted microscope. RESULTS: The cores of MG-63
      cellular spheres exhibited embryonic stem cell characteristics such as Nanog and
      Oct4 expession. The mTOR pathway was activated in the OSC and the expression of
      mTOR mRNA was higher in OSC (0.761 +/- 0.080) than that in OS (0.406 +/- 0.090, P
      < 0.05) by semi-quantitative PCR. RT-PCR showed that the expression of mTOR mRNA
      was lower in OSCs treated with 100 nmol/L rapamycin (0.961 +/- 0.060) than that
      with 0 nmol/L rapamycin (1.654 +/- 0.246, P < 0.05). Cell counting kit-8 (CCK-8)
      assay showed that the proliferation of OC treated with 20, 50 and 100 nmol/L
      rapamycin was significantly inhibited, compared with that with 0 nmol/L rapamycin
      (P < 0.05). Compared with 0 nmol/L rapamycin, the proliferation of OSC treated
      with 20 and 50 nmol/L rapamycin was not significantly inhibited (P > 0.05), but
      that with 100 nmol/L rapamycin was significantly inhibited (P < 0.05). The invert
      microscopic observation revealed that rapamycin inhibited the formation of OSC
      spheres. CONCLUSIONS: Rapamycin can effectively inhibit cell proliferation and
      the ability of sphere formation of OSCs. It will provide a basis for a novel
      therapeutic approach in osteosarcoma chemotherapy regimens.

PMID- 23879997
TI  - [Molecular mechanism of chemosensitization to paclitaxel in human melanoma cells
      induced by targeting the EGFR signaling pathway].
AB  - OBJECTIVE: To study the molecular mechanism of epidermal growth factor receptor
      (EGFR) signaling pathway in mediating paclitaxel-resistance and improving
      paclitaxel sensitivity in human melanoma A375 cells. METHODS: Human melanoma cell
      line A375 cells were treated with different concentrations of paclitaxel with or
      without 20 umol/L AG1478 (EGFR inhibitor), 40 umol/L PD98059 (extracellular
      signal conditioning kinase (ERK) 1/2 blockers) or 10 umol/L LY294002 (PI3K
      inhibitor). MTT method was used to measure the proliferation of A375 cells. Flow
      cytometry was used to detect cell cycle and apoptosis in the A375 cells. The
      expressions of P-EGFR, P-ERK and P-AKT proteins were determined by Western blot
      analysis. RESULTS: Paclitaxel (0.001 umol/L to 0.1 umol/L) inhibited the growth
      of A375 cells (P < 0.01) and induced apoptosis (P < 0.05) in a dose- and time
      dependent manner. AG1478 (20 umol/L) increased the 0.01 umol/L paclitaxel-induced
      inhibition rate from 38.5% to 62.6% at 72 h. Different doses of paclitaxel
      induced apoptosis in A375 cells by different ways, in which G0/G1 phase cells
      were decreased and mitotic phase was prolonged at 0.01 umol/L, and cell cycle
      arrest at G2/M phase by 0.1 umol/L paclitaxel. When DNA damage occurred in A375
      cells exposed to paclitaxel, expression of P-EGFR, P-ERK and P-AKT proteins was
      increased. When EGFR signaling pathway was blocked, paclitaxel did not activate
      MAPK signaling pathway or PI3K/AKT signaling pathway and did not change its
      effect on cell cycle in vitro. When EGFR was inhibited by 20 umol/L tyrophostin
      AG1478, the 0.001 and 0.01 umol/L paclitaxel-induced early apoptosis rate in A375
      cells was increased by 1.73- and 1.80-fold, respectively. When the ERK signaling
      was blocked by 40 umol/L PD98059, the 0.001 and 0.01 umol/L paclitaxel-induced
      early apoptosis rate in A375 cells was increased by 2.73- and 2.25-fold,
      respectively. When the AKT signaling was blocked by 10 umol/L LY294002, the 0.001
      and 0.01 umol/L paclitaxel-induced early apoptosis rate in A375 cells was
      increased by 2.02- and 1.46-fold, respectively. CONCLUSIONS: Human melanoma A375
      cells produce resistance to paclitaxel (0.001 to 0.1 umol/L) by activating MAPK
      signaling and PI3K/AKT signaling pathways. Targeting EGFR, ERK and AKT signaling
      pathways significantly enhances the cytotoxic effect of paclitaxel on human
      melanoma cells.

PMID- 23879998
TI  - [EGFR-ERK signaling pathway down-regulates miRNA-145 in lung cancer cells].
AB  - OBJECTIVE: To investigate the relationship between EGFR activation and down
      regulation of miRNA-145 in lung cancer. METHODS: Normal human lung epithelia cell
      line (BEAS-2B), human lung adenocarcinoma cell lines with wild-type EGFR (A549
      and H292) and human lung adenocarcinoma cell lines with EGFR mutation (H1975 and
      H1650) were chosen in this study. The levels of miRNA-145 and p-EGFR were
      determined by quantitative real-time PCR (qRT-PCR) and Western blotting,
      respectively, and the relationship between p-EGFR and miRNA-145 levels was
      analyzed. The miRNA-145 levels were determined by qRT-PCR after activating EGFR
      with EGF or blocking EGFR signal pathway with AG1478. In addition, ERK1/2
      inhibitor U0126 was used to inhibit ERK1/2 activation and then the expression of
      miRNA-145 was detected. RESULTS: The miRNA-145 levels were closely negatively
      related with p-EGFR in lung cancer cells (r = -0.926, P = 0.024). EGF down
      regulated miRNA-145 expression, particularly in BEAS-2B cells (53.0%; t = 30.993,
      P = 0.001) and A549 cells (42.6%; t = 14.326, P = 0.005).The miRNA-145 was up
      regulated after inhibiting p-EGFR with AG1478, and significantly enhanced by
      67.5% in H1975 cells when treated with AG1478 (t = 8.269, P = 0.014). The ERK1/2
      signal pathway was activated by p-EGFR. U0126 restored the miRNA-145 down
      regulation induced by EGFR-activation in lung cancer cells. CONCLUSION: The
      activation of EGFR down-regulates miRNA-145 expression through ERK1/2 in lung
      cancer cells.

PMID- 23879999
TI  - [Correlation of blood flow assessed by CT perfusion imaging and microvascular
      ultrastructure in non-small cell lung cancer: a preliminary study].
AB  - OBJECTIVE: To investigate the correlation between blood flow assessed by CT
      perfusion imaging and characteristics of microvascular ultrastructure in non
      small cell lung cancer (NSCLC). METHODS: twenty-eight patients with non-small
      cell lung cancer proven surgically and pathologically underwent perfusion CT
      examination. The patients were divided into a hyper-perfusion group and a hypo
      perfusion group by the median value of blood flow, and then the differences of
      microvascular ultrastructure in the two groups were analyzed. RESULTS: The median
      BF value of the 28 patients was 36.40 ml*100 g(-1)*min(-1). Take this median
      value as the boundary, the group with hypo-perfusion showed a significantly lower
      BF value than the group with hyper-perfusion [(30.84 +/- 4.79) ml*100 g(-1)*min(
      1) vs. (49.67 +/- 10.89) ml*100 g(-1)*min(-1), t = -5.925, P < 0.001]. The group
      with lymph node metastasis showed a significantly lower BF value than the group
      without lymph node metastasis [(30.78 +/- 5.24) ml*100 g(-1)*min(-1) vs. (50.73
      +/- 11.16) ml*100 g(-1)*min(-1), t = 3.490, P = 0.015]. The maturity of
      microvessels of the hyper-perfusion group was higher than that of the hypo
      perfusion group. Under the electron microscope, the microvessels in the hypo
      perfusion group showed a more narrow lumen, poorer integrity of basement
      membrane, a more close relationship between cancer cells and microvascular wall,
      and cancer cells were more easily seen in the microvascular lumen. CONCLUSION:
      The blood flow value of CT perfusion imaging may be related with the abnormal
      microvascular ultrastructure, and may be helpful to the prediction of metastasis
      risk in NSCLC.

PMID- 23880000
TI  - [Robo1 expression in non-small cell lung cancer and its brain metastasis].
AB  - OBJECTIVE: To detect the expression of Robo1 in lung cancer tissues, adjacent non
      cancerous tissues as well as lung cancer brain metastasis, and explore the
      correlation of Robo1 expression to lung cancer brain metastasis. METHODS: SP
      (streptavidin-peroxidase) staining method was used to examine the Robo1
      expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non
      cancerous tissues and 72 cases of lung cancer with single brain metastasis
      (without metastasis in other organs). The Robo1 expression was further examined
      in 17 self control cases with lung cancer tissues and their brain metastasis
      tissues. The results were assessed by Kaplan-Meier analysis and log-rank test.
      RESULTS: The positive expression rate of Robo1 among adjacent non-cancerous
      tissues, lung cancers tissues and the lung cancer brain metastasis tissues were
      1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant
      differences were detected among them (P < 0.05). During the 17 self control
      cases, the positive expression rate of Robo1 in lung cancer tissue and their
      brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant
      difference between them (P < 0.01). Among the 72 cases of lung cancer brain
      metastasis, the median survival time of cases with positive Robo1 expression was
      10 months, significantly shorter than that of cases with negative expression of
      Robo1 (17 months, P < 0.05). CONCLUSIONS: The positive expression rate of Robo1
      was increased in sequence from the lowest in adjacent non-cancerous tissues,
      intermediate in the lung cancer tissues to highest in the lung cancer brain
      metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is
      negatively correlated with the prognosis of patients with lung cancer brain
      metastasis. Robo1 may promote the genesis and progression of lung cancer and lung
      cancer brain metastasis as a cancer-promoting oncogene.

PMID- 23880001
TI  - [Expression of transcription factor SOX4 and its clinical significance in female
      lung cancer patients in Xuanwei area, Yunnan Province].
AB  - OBJECTIVE: To investigate the expression of transcription factor SOX4 in lung
      cancer tissues of female patients in Xuanwei area, Yunnan Province, and explore
      its correlation with clinicopathological characteristics and prognosis of the
      female patients. METHODS: Real-time PCR was applied on lung cancer specimens and
      their corresponding normal lung tissues from 96 female cases of Xuanwei area to
      assess the expression of SOX4 mRNA. Immunohistochemical staining was performed to
      investigate the SOX4 protein expression, and further to elucidate its correlation
      with clinicopathological characteristics and prognosis. RESULTS: The expression
      level of SOX4 mRNA in the cancer tissues (2.53 +/- 1.65) was significantly higher
      than that of matched normal tissues (1.43 +/- 1.14, P = 0.003).
      Immunohistochemical staining showed that there were 53.1% (51/96) positive
      expression of SOX4 protein in the cancer tissue and only 26.0% (25/96) in matched
      normal tissue (P < 0.001). The expression of SOX4 protein had a significant
      correlation with clinical stage, lymph node metastasis and differentiation of
      tumor (P < 0.05). The survival analysis by Kaplan-Meier method showed that
      patients with positive expression of SOX4 protein, lymph node metastasis and
      advanced tumor stage had a significantly shorter median survival time (P < 0.05).
      Cox regression survival analysis showed that pathological grade was a significant
      independent factor affecting prognosis. CONCLUSIONS: The expressions of SOX4 mRNA
      and protein are significantly up-regulated in Xuanwei female lung cancer
      patients. Patients with positive SOX4 expression have a shorter median survival
      time. SOX4 protein expression level combined with pathological grade can be used
      as a prognostic indicator of female lung cancer patients in Xuanwei area, Yunnan
      Province.

PMID- 23880002
TI  - [Clinicopathological features and prognostic factors of breast cancer patients
      with inguinal lymph node metastases: a report of 17 cases].
AB  - OBJECTIVE: To analyze the clinicopathological features and prognostic factors of
      breast cancer patients with inguinal lymph node metastases. METHODS: Seventeen
      breast cancer patients with inguinal lymph node metastases were treated from
      January 1999 to December 2010 in our cancer center. All of the patients had a
      history of breast cancer without other primary cancer. Their clinicopathological
      characteristics and prognostic factors were surveyed. RESULTS: The frequency of
      breast cancer cases with inguinal lymph node metastaseis consisted of 0.11% of
      the total number of breast cancer patients in the same period. Two patients
      (11.8%) had inguinal lymph node metastasis only, and multi-site metastases were
      observed in the remaining 15 (88.2%) patients. The number of ER- and/or PR
      positive and negative were 10 (58.8%) and 7 (41.2%) cases, respectively, and
      among the 13 cases who underwent HER-2 test, the number of HER-2-positive was 4
      (30.8%). For the 16 patients who underwent surgery, 9 patients were detected with
      metastatic axillary lymph nodes equal or greater than 4. All of the 17 patients
      were treated with chemotherapy.The median follow-up time was 156 months. The 5
      year overall survival rate was 49.9%. Univariate analysis revealed that
      metastatic axillary lymph nodes >= 4, ER- and(or) PR-negative, adjuvant
      chemotherapy <= 6 cycles, disease stage as III/IV at diagnosis and the period
      from diagnosis of breast cancer to the occurrence of inguinal lymph node
      metastasis <= 36 months were predictors of shorter PFS (P < 0.05). Metastatic
      axillary lymph nodes >= 4, ER- and(or) PR-negative, adjuvant chemotherapy <= 6
      cycles, primary recurrence as multiple distant metastases, the period from
      diagnosis of breast cancer to the occurrence of inguinal lymph nodes metastasis
      <= 36 months and pleural effusion were predictors of shorter OS (P < 0.05).
      Multivariate analysis revealed that the period from diagnosis of breast cancer to
      the occurrence of inguinal lymph node metastasis was an independent prognostic
      factor concerning PFS (P < 0.05). CONCLUSIONS: The prognostic factors of breast
      cancer patients with inguinal lymph node metastases include the number of
      metastatic axillary lymph nodes, ER and(or) PR status, the cycles of adjuvant
      chemotherapy, type of primary recurrence, the period from diagnosis of breast
      cancer to the occurrence of inguinal lymph node metastasis and pleural effusion.
      Regular and complete physical examination after surgery as well as prompt
      intensive treatment for high-risk patients may have positive significance in the
      treatment of such type of patients. However, a type of more reasonable and
      individualized treatment is warranted in future studies.

PMID- 23880003
TI  - [Analysis of prognostic factors after radical resection in 628 patients with
      stage II or III colon cancer].
AB  - OBJECTIVE: To analyze the clinicopathologic factors related to recurrence and
      metastasis of stage II or III colon cancer after radical resection. METHODS: The
      clinical and pathological data of 628 patients with stage II or III colon cancer
      after radical resection from Jan. 2005 to Dec. 2008 in our hospital were
      retrospectively reviewed and analyzed. RESULTS: The overall recurrence and
      metastasis rate was 28.5% (179/628). The 5-year disease-free survival (DFS) rate
      was 70.3% and 5-year overall survival (OS) rate was 78.5%. Univariate analysis
      showed that age, smoking intensity, depth of tumor invasion, lymph node
      metastasis, TNM stage, gross classification, histological differentiation, blood
      vessel tumor embolus, tumor gross pathology, multiple primary tumors,
      preoperative and postoperative serum concentration of CEA and CA19-9, and the
      regimen of adjuvant chemotherapy were correlated to recurrence and metastasis of
      colon cancer after radical resection. Multivariate analysis showed that regional
      lymph node metastasis, TNM stage, the regimen of postoperative adjuvant
      chemotherapy, and preoperative serum concentration of CEA and CA19-9 were
      independent factors affecting the prognosis of colon cancer patients. CONCLUSION:
      Regional lymph node metastasis, TNM stage, elevated preoperative serum
      concentration of CEA and CA19-9, the regimen of postoperative adjuvant
      chemotherapy with single fluorouracil type drug are independent risk factors of
      recurrence and metastasis in patients with stage II-III colon cancer after
      radical resection.

PMID- 23880004
TI  - [Analysis of risk factors for spontaneous rupture of hepatocellular carcinoma].
AB  - OBJECTIVE: To assess the risk factors for spontaneous rupture of hepatocellular
      carcinoma (SRHC). METHODS: A retrospective analysis of 34 consecutive patients
      with SRHC treated by emergency interventional embolization in our hospital from
      July 2003 to July 2011 was conducted. General condition, laboratory examination
      and imaging data were analyzed, and compared with the data of 34 patients with
      primary hepatocellular carcinoma but without rupture, randomly selected from 215
      concurrent patients. The patients with SRHC were selected for risk factor
      analysis, and the non-SRHC patients were taken as control group. RESULTS: No
      significant difference between the SRHC group and control group was found in age,
      sex, Child-Turcotte-Pugh (CTP) grade, Barcelona clinic liver cancer (BCLC) stage,
      HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, prothrombin time (PT), thrombin time (TT),
      international normalized ratio (INR), glucose (GLU), cirrhosis, portal tumor
      thrombus, the maximum diameter of tumor, location, and cholecystitis or
      cholelithiasis. The univariate analysis showed that activated partial
      thromboplastin time (APTT), lower or normal plasma fibrinogen (FIB) level, alpha
      fetoprotein (AFP), tumor protrusion > 1 cm above the liver surface were all
      associated with increased risk of SRHC (P < 0.05). Multivariate analysis only
      showed that lower or normal level of FIB (P = 0.033) and tumor protrusion > 1 cm
      above the liver surface (P = 0.041) were significant independent risk factors for
      SRHC. CONCLUSION: Lower or normal level of FIB and tumor protrusion > 1 cm above
      the liver surface are significant independent risk factors for spontaneous
      rupture of hepatocellular carcinoma.

PMID- 23880005
TI  - [Efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as
      the first-line therapy in elderly patients with advanced non-small cell lung
      cancer].
AB  - OBJECTIVE: To observe the clinical efficacy and safety of pemetrexed or
      gemcitabine combined with carboplatin as the first-line therapy in elderly
      patients with advanced non-small cell lung cancer (NSCLC). METHODS: Seventy
      patients aged 70 years or over with stage IIIb-IV NSCLC were equally and randomly
      divided into pemetrexed plus cisplatin group (PC) and gemcitabine plus
      carboplatin group (GC). Patients in the PC group received pemetrexed (PEM) 500
      mg/m(2) on day 1, and carboplatin (CBP) AUC5 on day 1 for 21-day cycle. Patients
      in the GC group received gemcitabine 1000 mg/m(2) on days 1 and 8, CBP AUC5 on
      day 1 for a 21-day cycle. RESULTS: In the PC and GC groups, CR 0 and 0, PR 10 and
      8, response rates 28.6% and 22.9% were observed, respectively. There was no
      statistically significant difference between the two groups (chi(2) = 0.299, P =
      0.584). The 1-year and 2-year survival rates of the PC and GC groups were 48.6%
      vs. 45.7% and 11.4% vs. 11.4%, respectively, with a median survival of 11.00 and
      10.00 months, without a statistically significant difference between the two
      groups (chi(2) = 0.01, P = 0.919). Regarding toxicities, the incidences of
      neutropenia/thrombocytopenia, nausea and vomiting (grade III ~ IV) in the GC
      group were significantly higher than those in the PC group (P < 0.05). According
      to the observer scale of lung cancer symptoms, the post-treatment scores improved
      in both the two groups, and with no significant difference between them (P >
      0.05). CONCLUSIONS: PC and GC show similar efficacy for elderly NSCLC patients,
      however, the toxicities in PC patients are lower than those in GC patients. Thus,
      pemetrexed combined with carboplatin is an effective chemotherapeutic regimen for
      advanced NSCLC in elderly patients.

PMID- 23880006
TI  - [Treatment of thoracolumbar tumors with total en bloc spondylectomy and the
      results of spinal stability reconstruction].
AB  - OBJECTIVE: To investigate the therapeutic effect of total en bloc spondylectomy
      (TES) for thoracolumbar tumors and the results of spinal stability
      reconstruction. METHODS: From January 2007 to June 2011 there were 18 patients
      with thoracolumbar tumors distributed in the thoracic vertebrae (n = 10) and
      lumbar vertebrae (n = 8). There were 7 haemangiomas, 5 giant cell tumors of bone,
      1 malignant schwannoma, 1 solitary plasmocytoma, 1 neuroblastoma, 1
      osteoblastoma, 1 metastatic malignant fibrous histiocytoma, and 1 metastasis of
      breast cancer. All the 18 patients were treated with improved TES under
      electrophysiological monitoring of spinal cord. Four patients were treated
      through one-stage combined anteroposterior approach and 14 patients through one
      stage posterior approach. The anterior reconstructions included titanium mesh
      cages filled with bone or bone cement in 15 cases, titanium mesh cage with
      strengthened rings in 2 cases and artificial vertebral body replacement in 1
      case. The posterior reconstruction included multiple segmental fixation with
      pedicle screw-rod system in 15 cases and short segmental fixation in 3 cases.
      Massive bone auto-graft was employed in 13 cases and fragmental bone graft in 5
      cases. RESULTS: The total en bloc spondylectomy was performed successfully in 15
      patients and unsuccessful in 3 whose spinal tumors were resected by piecemeal
      technique. In 15 patients with successfully performed TES, the duration of
      surgery was from 340 to 610 min (average, 450.7 min), the blood loss was from
      3000 to 10 200 ml (average, 4850 ml), and the intraoperative blood transfusion
      was from 2800 to 9600 ml (average, 4200 ml). The operation-related complications
      comprised hemopneumothorax, intercostal nerve pain, stress ulcer and bleeding,
      and so on. One year after operation, the patients with neurological dysfunction
      recovered from grade A to grade D in one patient, and to grade E in the other 14
      cases. The average visual analog scale (VAS) scores was 0.5. One patient with
      plasmacytoma and another one with L5 metastatic tumor suffered progression of the
      disease and were living with the diseases. The patient with metastatic malignant
      fibrous histiocytoma died of local recurrence and lung metastasis 16 months
      postoperatively. One patient with L4 neuroblastoma died of other reason and all
      the rest were free from relapse. The Cobb angle of upper and lower vertebral body
      adjacent to the involved vertebrae in sagittal plane was from -26.7 degrees  to
      12.0 degrees  (average, -2.57 degrees ) just postoperatively and from -17.5
      degrees  to 57.2 degrees  (average, 11.5 degrees ) at the last follow-up or
      before reoperation. There were 2 patients with screw-rod breakdown and 2 patients
      with internal fixation loosening. The measurement of titanium mesh cage subsided
      into adjacent vertebral bodies was average 7.5 mm. The revision surgery was
      performed in 3 patients, through combined anteroposterior approach in 2 and only
      posterior approach in 1 patient. CONCLUSIONS: TES significantly increases the
      therapeutic effect of spinal tumors, although accompanied with high difficulty
      and massive bleeding. In spinal stability reconstruction after total
      spondylectomy, it should be emphasized that posterior long segment fixation with
      pedicle screw-rod system, massive bone bridging graft and the application of
      thoracolumbosacral orthosis can achieve short-term firm fixation and long-term
      fusion-stabilization.

PMID- 23880007
TI  - [Analysis of surgical treatment of soft tissue sarcomas of the adductor
      compartment].
AB  - OBJECTIVE: To review the outcomes and complications of 21 consecutive patients
      with soft tissue sarcomas of the adductor compartment treated in our hospital
      from July 2006 to March 2012. METHODS: Medical records of 21 patients who
      underwent resection of soft tissue sarcomas of the adductor compartment were
      reviewed. Eight of the patients had primary operation, other eight had secondary
      radical excision, and five were admitted for tumor recurrence after operation in
      local hospitals. Six cases used gracilis or sartorius muscle to fill the cavity
      after removal of adductor muscle group. Fifteen patients underwent adjuvant
      treatment including radiotherapy and/or chemotherapy. RESULTS: Seven patients
      (33.3%) developed wound complications. Five required further surgery and two
      received dressing changes. All the patients were followed up for 3 to 60 months.
      During the follow-up period, no tumor recurrence was found in all the patients,
      only one case had multiple bone and pulmonary metastases, and two cases died (one
      for pulmonary metastasis at 11 months after surgery, and the other died of heart
      disease at 36 months post operation). CONCLUSIONS: Good local control rate can be
      achieved in patients with soft tissue sarcomas of the adductor compartment by
      using adductor muscle group resection, but it carries a relatively high rate of
      wound complications requiring proper management.

PMID- 23880008
TI  - [Long-term effect of repeated selective arterial embolization and curettage on
      high-level sacral giant cell tumor of bone].

PMID- 23880009
TI  - [Association of genetic variantions of circadian clock genes and risk of breast
      cancer].
AB  - OBJECTIVE: To investigate the relationship between genetic variantions of
      circadian clock genes and risk of breast cancer. METHODS: A case-control study
      including 406 breast cancer patients and 412 controls was conducted and genes
      Clock (rs2070062) and Per2 (rs2304672, rs2304669, rs934945) were genotyped by
      TaqMan real-time PCR. Unconditional logistic regression model was used to analyze
      the association between the genetic polymorphisms and breast cancer. RESULTS:
      Individuals with the rs2304669-TT genotype showed significantly increased breast
      cancer risk with the OR of 2.33 when compared with the individuals with rs2304669
      CC and CT genotypes (P = 0.001). In addition, the three haplotypes containing the
      risk T allele of rs2304669 were identified to be associated with increased breast
      cancer risk. However, it was found that rs2304672, rs2070062 and rs934945
      polymorphisms were not related with breast cancer risk. CONCLUSIONS: The locus
      rs2304669 on Per2 gene is associated with breast cancer risk. Genetic variation
      of circadian clock genes may increase the susceptibility to breast cancer.
      Therefore, it may become an important biomarker of susceptibility to breast
      cancer.

PMID- 23880010
TI  - Comparative assessment of absolute cardiovascular disease risk characterization
      from non-laboratory-based risk assessment in South African populations.
AB  - BACKGROUND: All rigorous primary cardiovascular disease (CVD) prevention
      guidelines recommend absolute CVD risk scores to identify high- and low-risk
      patients, but laboratory testing can be impractical in low- and middle-income
      countries. The purpose of this study was to compare the ranking performance of a
      simple, non-laboratory-based risk score to laboratory-based scores in various
      South African populations. METHODS: We calculated and compared 10-year CVD (or
      coronary heart disease (CHD)) risk for 14,772 adults from thirteen cross
      sectional South African populations (data collected from 1987 to 2009). Risk
      characterization performance for the non-laboratory-based score was assessed by
      comparing rankings of risk with six laboratory-based scores (three versions of
      Framingham risk, SCORE for high- and low-risk countries, and CUORE) using
      Spearman rank correlation and percent of population equivalently characterized as
      'high' or 'low' risk. Total 10-year non-laboratory-based risk of CVD death was
      also calculated for a representative cross-section from the 1998 South African
      Demographic Health Survey (DHS, n = 9,379) to estimate the national burden of CVD
      mortality risk. RESULTS: Spearman correlation coefficients for the non-laboratory
      based score with the laboratory-based scores ranged from 0.88 to 0.986. Using
      conventional thresholds for CVD risk (10% to 20% 10-year CVD risk), 90% to 92% of
      men and 94% to 97% of women were equivalently characterized as 'high' or 'low'
      risk using the non-laboratory-based and Framingham (2008) CVD risk score. These
      results were robust across the six risk scores evaluated and the thirteen cross
      sectional datasets, with few exceptions (lower agreement between the non
      laboratory-based and Framingham (1991) CHD risk scores). Approximately 18% of
      adults in the DHS population were characterized as 'high CVD risk' (10-year CVD
      death risk >20%) using the non-laboratory-based score. CONCLUSIONS: We found a
      high level of correlation between a simple, non-laboratory-based CVD risk score
      and commonly-used laboratory-based risk scores. The burden of CVD mortality risk
      was high for men and women in South Africa. The policy and clinical implications
      are that fast, low-cost screening tools can lead to similar risk assessment
      results compared to time- and resource-intensive approaches. Until setting
      specific cohort studies can derive and validate country-specific risk scores, non
      laboratory-based CVD risk assessment could be an effective and efficient primary
      CVD screening approach in South Africa.

PMID- 23880012
TI  - The association between possible stress markers and vocal symptoms.
AB  - OBJECTIVES/HYPOTHESIS: Stress reaction provokes changes in the body involving
      cardiovascular alterations, autonomic reactions, neuroendocrine and immunologic
      as well as psychoneuroimmunologic changes. Both the primary and secondary effect
      of stress reaction may be of consequence for vocal function. The purpose of this
      questionnaire study was to determine the effect of stress symptoms on the
      occurrence of vocal symptoms. The study also aimed at investigating whether a
      possible effect was different for men and women. METHODS: A total number of 1728
      participants completed a questionnaire concerning speech, language, and voice.
      Six vocal symptoms and four possible stress symptoms were included in the
      questionnaire. RESULTS: There was a significant association between stress
      symptoms and the occurrence of vocal symptoms. The occurrence of muscle tension
      or a lump in the throat was significant regarding all the four possible stress
      symptoms. There were also significant results concerning gender difference. All
      vocal symptoms and two of four stress symptoms were more common among women.
      CONCLUSIONS: Physical changes caused by the stress reaction may result in vocal
      symptoms as those presented in the study. Both vocal symptoms and stress symptoms
      were more common among women. Stress should preferably be acknowledged as a risk
      factor containing and possibly entailing a number of physiological,
      psychological, and behavioral symptoms affecting the voice negatively.

PMID- 23880011
TI  - Epstein Barr virus DNA analysis in blood predicts disease progression in a rare
      case of plasmablastic lymphoma with effusion.
AB  - BACKGROUND: In HIV-1-infected patients a long lasting CD4+ cell decline
      influences the host-EBV balance and thereby increases the risk for EBV related
      malignancies. In spite of a world-wide access to combination antiretroviral
      therapy (cART) there are still a considerable number of HIV-1-infected patients
      who will develop severe immunodeficiency. These undiagnosed HIV-1 infected
      patients, so called late testers, demonstrate an increased lymphoma risk,
      compared to patients diagnosed early. Consecutive individual screening for EBV
      DNA-load in late testers might be a useful predictor of emerging EBV-malignancy.
      METHODS: Patient biopsies and ascites were analyzed morphologically, by immuncyto
      histochemistry and in-situ hybridization. Viral DNA and RNA load were quantified
      by PCR. Cell lines from primary tumor and from ascites, were established in vitro
      and further analyzed. RESULT: We here report on a case of EBV-positive lymphoma
      in an AIDS patient, first presenting with pleural effusion and ascites and was
      thus initially considered a primary effusion lymphoma (PEL) but was later
      diagnosed as a plasmablastic lymphoma (PBL). The patient had responded to cART
      with undetectable HIV-RNA and increased CD4 cell count one year prior to lymphoma
      presentation. At the time of lymphoma diagnosis the HIV-RNA values were <50 RNA
      copies per mL blood (undetectable) and the CD4-positive cell count 170 *106/L.
      The lymphoma was CD45-negative and weakly CD22- and CD30-positive. The patient
      had a history of Kaposi sarcoma and HHV-8 seropositivity. The lymphoma biopsies,
      and three cell lines derived on different occasions from the tumor cell effusion,
      were all EBV-positive but HHV-8 negative.A noticeable EBV-DNA load decline was
      observed during the remission of the lymphoma following CHOP-therapy. The EBV-DNA
      load increased dramatically at the time of recurrence. CONCLUSION: EBV DNA load
      might be useful in monitoring the effect of lymphoma treatment as well as in
      estimating the risk of EBV-associated lymphoma in HIV-1 infected patients with
      pronounced immunosuppression.

PMID- 23880013
TI  - Bilobed perforator free flaps for combined hemitongue and floor-of-the-mouth
      defects.
AB  - INTRODUCTION: Combined hemiglossectomy and floor-of-the-mouth defects need
      accurate reconstructive planning to restore swallowing and speech function. The
      aim of this prospective study was to evaluate outcomes of the bilobed design
      applied to perforator free flaps for combined hemitongue and floor-of-the-mouth
      defects. PATIENTS AND METHODS: Twelve patients with a mean age of 71 years
      (range, 60-84) addressed to combined hemiglossectomy and floor-of-the-mouth
      resection and bilobed-shaped perforator free-flap reconstruction were
      prospectively enrolled. Defects were classified as follows: type 1, including
      only the anterior mobile portion of the tongue (n = 3); type 2, involving both
      mobile tongue and tongue base (n = 6); and type 3, including segmental
      mandibulectomy combined with a type 1 or type 2 defect (n = 3). The Kruskal
      Wallis and Bonferroni post hoc tests were used to compare outcomes. RESULTS: Type
      1 defects were reconstructed by three anterolateral thigh (ALT) perforator flaps;
      type 2 defects were reconstructed by four ALT flaps and two vertical deep
      inferior epigastric perforator flaps; and type 3 defects were restored by three
      osteocutaneous fibula flaps. Eleven flaps (91.6%) healed uneventfully, while one
      (8.4%) suffered a small area of skin necrosis whose revision did not compromise
      functional results. Six patients achieved normal intelligible speech, five had
      acceptable intelligible speech and one had unintelligible speech (p = 0.356).
      Swallowing function was considered normal in eight patients and with mild
      impairment in four (p = 0.178). Cosmesis resulted excellent in seven patients and
      good in five (p = 0.855). CONCLUSION: The bilobed-shaped perforator free flaps
      were shown to be a safe and predictable solution for combined hemitongue and
      floor-of-the-mouth defects providing optimal aesthetic and functional outcomes.

PMID- 23880014
TI  - A practical and objective approach to scar colour assessment.
AB  - Scarring is a significant clinical problem following dermal injury. However,
      scars are not a single describable entity and huge phenotypic variability is
      evident. Quantitative, reproducible inter-observer scar assessment is essential
      to monitor wound healing and the effect of scar treatments. Scar colour,
      reflecting the biological processes occurring within a scar, is integral to any
      assessment. The objective of this study was to analyse scar colour using the non
      invasive Eykona(r) Wound Measurement System (the System) as compared against the
      Manchester Scar Scale (MSS). Three dimensional images of 43 surgical scars were
      acquired post-operatively from 35 patients at 3-6 months and the colour
      difference between the scar and surrounding skin was calculated (giving DeltaLab
      values). The colourimetric results were then compared against subjective MSS
      gradings. A significant difference in DeltaLab values between MSS gradings of
      "slight mismatch" and "obvious mismatch" (p<0.025) and between "obvious mismatch"
      and "gross mismatch" (p<0.05) were noted. The System creates objective,
      reproducible data, without the need for any specialist expertise and compares
      favourably with the MSS. Greater scar numbers are required to further clinically
      validate this device--however, with this potential to calculate scar length,
      width, volume and other characteristics, it could provide a complete, objective,
      quantitative record of scarring throughout the wound-healing process.

PMID- 23880015
TI  - Human herpes virus 6 encephalitis in immunocompetent patient: an unusual
      neuroradiological presentation.

PMID- 23880016
TI  - Consensus guidelines on the neurologist's role in the management of neurogenic
      lower urinary tract dysfunction in multiple sclerosis.
AB  - OBJECTIVE: To review current management of neurogenic lower urinary tract
      dysfunction (NLUTD) in MS patients and give recommendations on the joint role of
      the neurologist and urologist in NLUTD management. METHODS: An algorithm for
      evaluation and referral of MS patients to urologists was created. It is an
      outcome of discussions about current knowledge, existing guidelines, and key
      issues during two Belgian consensus meetings attended by neurologists, urologists
      and other stakeholders involved in MS management. At these meetings, updated
      information on management of NLUTD in MS was exchanged and the neurologists'
      opinion on how to integrate this in the other aspects of care in MS patients was
      explored. RESULTS: Short evaluation of NLUTD in MS patients by neurologists and
      appropriate referral to urologists could accelerate proper diagnosis and
      treatment. Neurologists can play a central role in the inter-disciplinary
      communication on interactions between disease manifestations of MS and their
      treatments. CONCLUSION: The coordinating role of neurologists in NLUTD management
      may considerably improve QoL in MS patients. More research is needed to evaluate
      outcomes of urological assessments and treatment.

PMID- 23880017
TI  - Multiple sclerosis among Iranian-Arabs and Persians of Khuzestan: is there any
      ethnic difference?

PMID- 23880018
TI  - Association of vitamin D receptor gene polymorphisms and Parkinson's disease in
      Hungarians.
AB  - Vitamin D receptor (VDR) gene encodes a transcription factor that influences
      calcium homeostasis and immunoregulation, and may play a role in neurological
      disorders including Parkinson's disease (PD). The investigations of the
      association between VDR and PD in different populations revealed various results.
      In a present study 100 PD patients and 109 healthy controls from the Hungarian
      population were genotyped for four polymorphic sites (BsmI, ApaI, FokI and TaqI)
      in the VDR gene. The polymorphisms were determined by polymerase chain reaction
      and restriction fragment length polymorphism (PCR-RFLP). Our results demonstrate
      an association between the FokI C allele and PD; the frequency of the C allele
      was significantly higher in PD patients than in controls, suggesting that this
      polymorphism may have a role in the development of PD in these patients.

PMID- 23880019
TI  - Detection of copy number changes in genes associated with Parkinson's disease in
      Iranian patients.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder,
      after Alzheimer's disease. Genomic rearrangements are common mutations reported
      in PD patients. In this study, we investigated the prevalence of genomic
      rearrangements in a total of 232 Iranian PD patients, out of which 102 were
      sporadic early-onset (age-at-onset <= 45 years) and 51 had a family history. We
      used multiplex ligation-dependent probe amplification (MLPA) method to detect
      exon dosage changes. Two new improved probe kits, SALSA P051 and P052, were used
      and altogether alpha-synuclein, parkin, UCHL1, PINK1, DJ-1, LRRK2, GCH1, ATP13A2,
      CAV1, CAV2, LPA and TNFRSF9 genes were analyzed. Exon or whole-gene
      rearrangements were identified in 14 (13.7%) sporadic early-onset PD patients in
      parkin, alpha-synuclein and PINK1. Of familial PD patients 46 cases from 18
      families (35.3%) showed exon or whole-gene rearrangements in parkin, alpha
      synuclein, PINK1, DJ-1, and ATP13A2 genes. All changes were verified by
      quantitative PCR (qPCR). Novel mutations and unusual clinical features are
      reported in this study. Mutations in parkin were the predominant genetic cause in
      both early-onset and familial PD groups. Also the mutations observed in family PD
      group are more in number and diversity than the sporadic early-onset PD group.

PMID- 23880020
TI  - The role of the ipsilateral primary motor cortex in movement control after spinal
      cord injury: a TMS study.
AB  - Previous neuroimaging studies raised the hypothesis that enhanced activity in the
      ipsilateral motor cortex (M1) plays a contributing role in the compensation for
      the motor deficits resulting from a spinal cord injury (SCI). However, it is
      still unknown whether the activity in the ipsilateral M1 directly contributes to
      movement performance after SCI. To address this question, we evaluated in five
      subjects with chronic incomplete cervical SCI the effects of suprathreshold
      transcranial magnetic stimulation (TMS) to both hemispheres when a movement of
      the right and left hand was performed separately in the setting of a simple
      reaction time. We found that stimulation of each hemisphere resulted in delayed
      simple reaction times in the contralateral but not in the ipsilateral hand. These
      observations provide the first direct evidence in humans that the ipsilateral M1
      did not contribute significantly to motor task performance after SCI. 

PMID- 23880021
TI  - A new method for Schwann-like cell differentiation of adipose derived stem cells.
AB  - Peripheral nerve repair can be enhanced by Schwann cell transplantation, but the
      clinical application of this procedure is limited by donor site morbidity and the
      inability to quickly generate a sufficient number of cells. Thus, alternative
      cell systems for the generation of Schwann cells are desired. Schwann-like cell
      induced from adipose-derived stem cells (ADSCs) may be one of the ideal
      alternative cell systems for Schwann cell generation. Although co-culture with
      Schwann cells or chemicals combined with a mixture of glial growth factors are
      often utilized for Schwann cell-like differentiation of ADSCs, these methods are
      usually complicated or expensive. In this experiment, the rat sciatic nerve was
      cut, and then soaked in culture medium for two days. The treated culture medium
      was used as an induction agent after filtering. The obtained ADSCs were incubated
      with the above induction culture medium for five days. Then, expression of the
      typical Schwann cell markers, S-100 and GFAP proteins was determined by
      immunocytochemical staining and Western blotting. The results showed that almost
      all of the treated ADSCs displayed a spindle shape like morphology after being
      incubated with induction culture medium for 24h and expressed S-100 and GFAP
      proteins after five days. All of these characteristics of differentiated rat
      ADSCs were similar to genuine Schwann cells. Thus, this new method, which
      utilized trophic factors secreted from sciatic nerve leachate, was capable of
      inducing ADSC differentiation into Schwann-like cell. 

PMID- 23880022
TI  - The influence of orexins on ethanol-induced behavioral sensitization in male
      mice.
AB  - Recent evidence indicates the involvement of orexin in reward circuitry and drug
      addiction. In the present study we evaluated the role of orexin in ethanol
      induced behavioral sensitization. In the first experiment, Swiss male mice
      received seven administrations of saline or ethanol (2.2g/kg, i.p., chronic),
      every other day. On the last day of treatment, half of saline-treated mice
      received a saline injection (saline) whereas the other half received 2.2g/kg of
      ethanol (i.p., acute). Behavioral sensitization was assessed by locomotor
      activity tests and after the last one, immunoreactivity for orexin and Fos
      (ORX+Fos-ir) was assessed in the lateral hypothalamic area. Chronic ethanol
      treatment produced behavioral sensitization and a trend for greater ORX+Fos-ir.
      In the second experiment, mice were treated as in Experiment 1 and type 1 orexin
      receptor antagonist, SB334867 (20mg/kg), was administered before the ethanol
      challenge successfully blocking the expression of sensitization in mice
      chronically treated with EtOH. These results indicate that orexin plays a role in
      ethanol-induced behavioral sensitization. 

PMID- 23880024
TI  - Diagnostic value of minor salivary glands biopsy for the detection of Lewy
      pathology.
AB  - The recent demonstration of the presence of Lewy pathology in the submandibular
      glands of Parkinson's disease (PD) patients prompted us to evaluate the
      diagnostic performance of minor salivary gland biopsy for PD. Minor salivary
      glands were examined for Lewy pathology using phosphorylated alpha-synuclein
      antibody in 16 patients with clinically diagnosed PD and 11 control subjects with
      other neurological disorders. Abnormal accumulation of alpha-synuclein was found
      in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated
      alpha-synuclein immunoreactivity. Our results do not support the use of minor
      salivary glands biopsy for the detection of Lewy pathology in living subjects. 

PMID- 23880023
TI  - Genetic variation of GRIN1 confers vulnerability to methamphetamine-dependent
      psychosis in a Thai population.
AB  - GRIN1 is a gene that encodes the N-methyl-d aspartate (NMDA) receptor subunit1
      (NR1). Variations of GRIN1 have been identified as a risk factor for
      schizophrenia and drug dependence, supporting hypotheses of glutamatergic
      dysfunction in these disorders. Methamphetamine (METH) is a psychostimulant drug
      which can induce psychotic symptoms reminiscent of those found in schizophrenia;
      thus GRIN1 is a candidate gene for vulnerability to METH dependence or METH
      dependent psychosis. The present study examined two polymorphisms of GRIN1,
      rs11146020 (G1001C) and rs1126442 (G2108A), in 100 male Thai METH-dependent
      patients and 103 healthy controls using PCR-RFLP techniques. Neither polymorphism
      was significantly associated with METH dependence, although rs1126442 was highly
      significantly associated with METH-dependent psychosis, in which the A allele
      showed reduced frequency (P<0.00001). The present findings indicate that the
      rs1126442 of GRIN1 contributes to the genetic vulnerability to psychosis in METH
      dependent subjects in the Thai population.

PMID- 23880027
TI  - Complex phenotypes in asthma: current definitions.
AB  - Asthma is increasingly recognized as a heterogeneous disease. However,
      identification of different subgroups or phenotypes has been complex and
      controversial. The convergence of both clinical and statistical approaches to
      grouping patients and their characteristics, in association with increasing
      recognition of molecular patterns is now beginning to move the field forward.
      Integration of efficacy data with targeted molecular therapies will eventually
      lead to more complete understanding of these "molecular phenotypes" and
      eventually lead to the identification of fully defined endotypes. This process
      should improve our ability to treat more complex and severe forms of asthma.

PMID- 23880025
TI  - Evaluation of transcranial sonographic findings and MIBG cardiac scintigraphy in
      the diagnosis of idiopathic Parkinson's disease.
AB  - The diagnosis of idiopathic Parkinson's disease (IPD) is based on clinical
      criteria. In the last two decades several neuroimaging methods using transcranial
      sonography (TCS) or radiolabelled tracers such as the myocardial MIBG
      scintigraphy were applied to support diagnosis of IPD. They have been used
      independently of each other and their interrelation is not yet clear. In the
      present study we analyzed the relation between findings of TCS, MIBG
      scintigraphy, and clinical presentation in 42 patients with IPD who were
      clinically diagnosed and underwent clinical follow-up over >=3 years in order to
      confirm IPD diagnosis throughout the clinical course. The extent of substantia
      nigra hyperechogenicity (SN+) contralateral to the clinically more affected body
      side (SN(contra)) was compared to myocardial (123)I-MIBG uptake. SN(contra) did
      not correlate with the myocardial MIBG uptake (r = -0.10; p = 0.52). Both
      myocardial MIBG uptake and TCS did not correlate significantly with Hoehn and
      Yahr stage (r = -0.03; p = 0.87 and r = -0.10; p = 0.54, respectively).
      Sensitivity of TCS in the diagnosis of IPD was 79%, of MIBG scintigraphy 81%. The
      combination of both measurements reached a sensitivity of 95%. TCS and MIBG
      scintigraphy may disclose complementary aspects of IPD. The combined use of both
      neuroimaging methods might improve the diagnostic sensitivity regarding IPD.

PMID- 23880028
TI  - Role of shellfish hatchery as a reservoir of antimicrobial resistant bacteria.
AB  - The main aim of this study was to determine the occurrence of resistant bacteria
      in florfenicol-treated and untreated scallop larval cultures from a commercial
      hatchery and to characterize some selected florfenicol-resistant strains. Larval
      cultures from untreated and treated rearing tanks exhibited percentages of
      copiotrophic bacteria resistant to florfenicol ranging from 0.03% to 10.67% and
      0.49-18.34%, respectively, whereas florfenicol resistance among oligotrophic
      bacteria varied from 1.44% to 35.50% and 3.62-95.71%, from untreated and treated
      larvae, respectively. Florfenicol resistant microbiota from reared scallop larvae
      mainly belonged to the Pseudomonas and Pseudoalteromonas genus and were mainly
      resistant to florfenicol, chloramphenicol, streptomycin and co-trimoxazole. This
      is the first study reporting antimicrobial resistant bacteria associated to a
      shellfish hatchery and the results suggest that a continuous surveillance of
      antimicrobial resistance even in absence of antibacterial therapy is urgently
      required to evaluate potential undesirable consequences on the surrounding
      environments. 

PMID- 23880029
TI  - In-home hierarchical posture classification with a time-of-flight 3D sensor.
AB  - A non-invasive technique for posture classification suitable to be used in
      several in-home scenarios is proposed and preliminary validation results are
      presented. 3D point cloud sequences were acquired using a single time-of-flight
      sensor working in a privacy preserving modality and they were processed with a
      low power embedded PC. In order to satisfy different application requirements
      (e.g. covered distance range, processing speed and discrimination capabilities),
      a twofold discrimination approach was investigated in which features were
      hierarchically arranged from coarse to fine by exploiting both topological and
      volumetric representations. The topological representation encoded the intrinsic
      topology of the body's shape using a skeleton-based structure, thus guaranteeing
      invariance to scale, rotations and postural changes and achieving a high level of
      detail with a moderate computational cost. On the other hand, using the
      volumetric representation features were described in terms of 3D cylindrical
      histograms working within a wider range of distances in a faster way and also
      guaranteeing good invariance properties. The discrimination capabilities were
      evaluated in four different real-home scenarios related with the fields of
      ambient assisted living and homecare, namely "dangerous event detection",
      "anomalous behaviour detection", "activities recognition" and "natural human
      ambient interaction". For each mentioned scenario, the discrimination
      capabilities were evaluated in terms of invariance to viewpoint changes,
      representation capabilities and classification performance, achieving promising
      results. The two feature representation approaches exhibited complementary
      characteristics showing high reliability with classification rates greater than
      97%. 

PMID- 23880030
TI  - An augmented reality (AR)-based vocational task prompting system for people with
      cognitive impairments.
AB  - This study assessed the possibility of training three people with cognitive
      impairments using an augmented reality (AR)-based task prompting system. Using AR
      technology, the system provided picture cues, identified incorrect task steps on
      the fly, and helped users make corrections. Based on a multiple baseline design,
      the data showed that the three participants considerably increased their target
      response, which improved their vocational job skills during the intervention
      phases and enabled them to maintain the acquired job skills after intervention.
      The practical and developmental implications of the results are discussed. 

PMID- 23880026
TI  - Sleep and impulsivity in Parkinson's disease.
AB  - BACKGROUND: Impulsive behavior and poor sleep are important non-motor features of
      Parkinson's disease (PD) that negatively impact the quality of life of patients
      and their families. Previous research suggests a higher level of sleep complaints
      in PD patients who demonstrate impulsive behaviors, but the nature of the sleep
      disturbances has yet to be comprehensively tested. METHODS: Consecutive
      idiopathic PD patients (N = 143) completed the Minnesota Impulse Disorder
      Interview and a sleep questionnaire that assessed sleep efficiency, excessive
      daytime sleepiness, restless legs symptoms, snoring, dreams/nightmares, and
      nocturia. Patients were also given a Unified Parkinson's Disease Rating Scale
      motor examination and they completed cognitive testing. RESULTS: Impulsive PD
      patients endorsed more sleep complaints than non-impulsive PD patients. The group
      difference was primarily attributable to poor sleep efficiency (e.g., greater
      nocturnal awakenings), p < .01, and greater daytime sleepiness, p < .01, in the
      impulsive PD patients. Interestingly, restless legs symptoms were also greater in
      the impulsive PD patients, p < .05. The results could not be explained by
      medications or disease severity. CONCLUSIONS: Poor sleep efficiency, restless
      legs symptoms, and increased daytime sleepiness are associated with impulsivity
      in PD. Longitudinal studies are needed to determine whether sleep disturbances
      precede impulsivity in PD.

PMID- 23880031
TI  - Comparing participation in out of school activities between children with visual
      impairments, children with hearing impairments and typical peers.
AB  - Hearing or visual impairments may negatively affect child's development and
      participation. Yet the literature about participation of children with hearing or
      visual impairments is insufficient. The present study aimed to compare
      participation patterns of children with visual impairments to those of children
      with hearing impairments and to typical peers and to examine the correlations
      between participation and socio-demographic parameters in each group.
      Participants were 70 children between the ages of 6-11: 25 with hearing
      impairments, 20 with visual impairments and 25 typical peers. All children filled
      the Children's Assessment of Participation and Enjoyment (CAPE). This self-report
      refers to participation in daily out of school activities. Children with hearing
      or visual impairments showed significant limited participation compared to
      typical peers, expressed in lower number of activities, lower participation
      intensity; more activities performed at home and with someone else. The limited
      participation was more emphasized among children with visual impairments. Socio
      demographic variables (age, mother's education and socio-economic level)
      correlated with participation dimensions in both study groups. In conclusion,
      children with hearing or visual impairments may have restricted participation in
      out of school activities. Socio-demographic parameters may play a role in
      encouraging child's participation. Participation among these populations should
      be further studied in order to assist service providers to create intervention
      programs together with the child, for enhancing his/her inclusion in the
      community. 

PMID- 23880032
TI  - Nailfold capillary patterns in healthy subjects: a real issue in capillaroscopy.
AB  - Nailfold capillaroscopy has been extensively applied in a broad spectrum of
      pathologic conditions, but very few data have been published in healthy
      individuals. The aim of this study was to describe the nailfold capillary
      findings on a large series of healthy subjects using the video-capillaroscopy
      technique. Nailfold capillaries were studied based on their morphology,
      dimensions and density. Then, to evaluate jointly the association between
      different capillary findings in groups of subjects which were homogeneous for
      their characteristics, cluster analysis was performed. The results (median) of
      capillary measurements were as follows: loop length 207MUm, external diameter
      39MUm, internal diameter 17MUm, apical diameter 17MUm, and intercapillary
      distance 143MUm. Based on the cluster analysis three major "normal" morphologic
      capillaroscopic patterns were depicted: 1) the "normal" pattern mainly with 2 to
      5 U-shaped loops/mm and <=2 tortuous loops/mm; 2) the "perfect normal" pattern
      with >=5 U-shaped loops/mm and 3) the "unusual normal" with at least 1 meandering
      or bushy loop, or at least 1 microhemorrhage, or with >4 crossed loops/mm.
      Regarding the loop measurements, the majority of subjects had a median of
      7capillaries/mm with a median length of 198MUm. 

PMID- 23880033
TI  - Linking appearance to neural activity through the study of the perception of
      lightness in naturalistic contexts.
AB  - The present paper deals with the classical question how a psychological
      experience, in this case apparent lightness, is linked by intervening neural
      processing to physical variables. We address two methodological issues: (a) how
      does one know the appropriate physical variable (what is the right x?) to look
      at, and (b) how can behavioral measurements be used to probe the internal
      transformation that leads to psychological experience. We measured so-called
      lightness transfer functions (LTFs), that is the functions that describe the
      mapping between retinal luminance and perceived lightness for naturalistic
      checkerboard stimuli. The LTFs were measured for different illumination
      situations: plain view, a cast shadow, and an intervening transparent medium.
      Observers adjusted the luminance of a comparison patch such that it had the same
      lightness as each of the test patches. When the data were plotted in luminance
      luminance space, we found qualitative differences between mapping functions in
      different contexts. These differences were greatly diminished when the data were
      plotted in terms of contrast. On contrast-contrast coordinates, the data were
      compatible with a single linear generative model. This result is an indication
      that, for the naturalistic scenes used here, lightness perception depends mostly
      on local contrast. We further discuss that, in addition to the mean adjustments,
      one may find it useful to consider also the variability of an observer's
      adjustments in order to infer the true luminance-to-lightness mapping function. 

PMID- 23880034
TI  - A rice fungicide blasticidin S efficiently binds Cu(II) ions and prevents DNA
      from metal-induced damage.
AB  - Blasticidin S is a representative of the aminoacylnucleoside class of antibiotics
      and it possesses fungicidal properties against the virulent fungus which causes a
      serious rice blast disease in Asia. It is widely used to control rice blast by
      foliar application as a crop protection agent. Serious copper contamination is
      observed in some areas of China. Moreover, some paddy soils present a potential
      risk of copper accumulation in the human body through the food chain, leading to
      several disorders. This work presents the results of combined potentiometric and
      spectroscopic (UV-visible, EPR, CD, NMR) data which lead to the conclusion that
      the antibiotic is capable of binding copper, and the resulting complexes are
      likely to form in the soil. The process of complex formation has a potential
      influence on the population feeding on a rice-based diet. Moreover, the results
      of electrophoretic experiments revealed that complexes do not cleave DNA. On the
      contrary, the presence of blasticidin S may prevent DNA from a Cu(II)-induced
      damage. 

PMID- 23880037
TI  - Sudomotor function assessment as a screening tool for microvascular complications
      in type 2 diabetes.
AB  - Sudoscan, a non invasive, quick, and simple method to measure sweat function, was
      evaluated as a screening tool for microvascular complications in type 2 diabetes.
      AUC of the ROC curve for detection of microvascular complication was 0.75 for an
      autonomic risk score, with a sensitivity of 82% and a specificity of 61%. 

PMID- 23880035
TI  - Relationship between herd-level incidence rate of energy-related postpartum
      diseases, general risk factors and claw lesions in individual dairy cows recorded
      at maintenance claw trimming.
AB  - BACKGROUND: Laminitis and energy-related postpartum diseases share several risk
      factors, indicating a common etiology. Thus, a herd's incidence rate of energy
      related postpartum diseases, such as displaced abomasum and clinical ketosis,
      might reflect the likelihood of cows to suffer from laminitis-related claw
      lesions. The aim of this study was to investigate the association between herd
      level incidence rate of displaced abomasum and clinical ketosis, general risk
      factors, and claw lesions in individual cows recorded at maintenance claw
      trimming. METHODS: The dataset consisted of 6773 trimmings, performed between
      2004 and 2006 by professional trimmers, from 3607 Swedish Red and Swedish
      Holstein cows in 26 herds. The herds were classified as having a high,
      inconsistent-high or low incidence rate of energy-related postpartum diseases,
      based on the number of recorded cases of veterinary-diagnosed displaced abomasum
      and clinical ketosis in the Swedish national animal disease recording system
      during 2002 to 2006, and observations and interviews in connections with herd
      visits. Generalized linear mixed models were used to investigate the association
      between herd-level incidence rate of energy-related postpartum diseases and
      laminitis-related lesions including sole ulcer and sole hemorrhage; and hygiene
      related lesions including interdigital dermatitis, digital dermatitis, heel-horn
      erosion, verrucose dermatitis, and interdigital hyperplasia; and absence of any
      claw lesion. Systematic effects, including first-order interactions, with P <
      0.05 were included in the models. Herd classification was forced into the models,
      and a random effect of herd was included. RESULTS: In comparison to herds with a
      high incidence rate of energy-related postpartum diseases, low-incidence herds
      showed a lower odds ratio (OR; 0.2) for laminitis-related lesions in cows trimmed
      during the summer months. Low-incidence herds also showed numerically lower OR
      estimates for laminitis-related lesions in all parity classes and a numerically
      lower OR for hygiene-related lesions. In addition, low-incidence herds showed
      tendencies towards a numerically higher OR for absence of any lesion,
      irrespective of trimming season or parity. CONCLUSIONS: Only a few statistically
      significant associations were found, but several tendencies pointed towards
      better claw health in herds with low as compared with high incidence rate of
      energy-related postpartum diseases.

PMID- 23880038
TI  - Clinical value of inflammatory urinary biomarkers in overt diabetic nephropathy:
      a prospective study.
AB  - AIMS: The evolution of diabetic nephropathy is incompletely accounted by current
      clinical tools. New biomarkers may refine patient assessment and help monitor
      therapy. We compared the added predictive value of 7 candidate inflammatory
      urinary biomarkers to known risk factors of progression. METHODS: We
      prospectively followed 83 patients with overt diabetic nephropathy for a median
      2.1 years and obtained repeated measurements of proteinuria, IL-1beta, IL-6, IL
      8, MCP-1, TNF-alpha, TGF-beta1, and PAI-1. RESULTS: Patients had an initial
      estimated glomerular filtration rate of 25 +/- 9 mL/min/1.73 m(2), blood pressure
      of 142/69 mmHg and used a median of 4 anti-hypertensive medications over the
      course of the study. The observed rate of renal function decline was 2.9 +/- 3.0
      mL/min/1.73 m(2)/year. All urinary biomarkers levels were collinear and for each
      one except IL-1beta, elevated levels predicted a more rapid progression. MCP-1
      was the only biomarker increasing during follow-up, which also correlated with a
      worst outcome. Using multivariate linear regression adjusting for clinical risk
      factors of progression, urinary MCP-1 and TGF-beta1 predicted progression
      independently and additively to the degree of proteinuria. We dichotomized these
      3 biomarkers and observed a renal function decline with 0, 1, 2 or 3 elevated
      biomarkers of -0.8 +/- 1.4, -2.1 +/- 2.1, -4.2 +/- 2.8 and -6.0 +/- 2.8
      mL/min/1.73 m(2)/year, respectively (p<0.001). CONCLUSIONS: Multiple urinary
      biomarkers predict outcome in overt diabetic nephropathy. However, urinary MCP-1
      and TGF-beta1 are also independent and additive to proteinuria in predicting the
      rate of renal function decline and could serve as useful clinical tools in
      patient risk stratification.

PMID- 23880036
TI  - 3H-deprenyl and 3H-PIB autoradiography show different laminar distributions of
      astroglia and fibrillar beta-amyloid in Alzheimer brain.
AB  - BACKGROUND: The pathological features in Alzheimer's disease (AD) brain include
      the accumulation and deposition of beta-amyloid (Abeta), activation of astrocytes
      and microglia and disruption of cholinergic neurotransmission. Since the
      topographical characteristics of these different pathological processes in AD
      brain and how these relate to each other is not clear, this motivated further
      exploration using binding studies in postmortem brain with molecular imaging
      tracers. This information could aid the development of specific biomarkers to
      accurately chart disease progression. RESULTS: In vitro binding assays
      demonstrated increased [3H]-PIB (fibrillar Abeta) and [3H]-PK11195 (activated
      microglia) binding in the frontal cortex (FC) and hippocampus (HIP), as well as
      increased binding of [3H]-L-deprenyl (activated astrocytes) in the HIP, but a
      decreased [3H]-nicotine (alpha4beta2 nicotinic acetylcholine receptor (nAChR))
      binding in the FC of AD cases compared to age-matched controls. Quantitative
      autoradiography binding studies were also performed to investigate the regional
      laminar distributions of [3H]-L-deprenyl, [3H]-PIB as well as [125I]-alpha
      bungarotoxin (alpha7 nAChRs) and [3H]-nicotine in hemisphere brain of a typical
      AD case. A clear lamination pattern was observed with high [3H]-PIB binding in
      all layers and [3H]-deprenyl in superficial layers of the FC. In contrast, [3H]
      PIB showed low binding to fibrillar Abeta, but [3H]-deprenyl high binding to
      activated astrocytes throughout the HIP. The [3H]-PIB binding was also low and
      the [3H]-deprenyl binding high in all layers of the medial temporal gyrus and
      insular cortex in comparison to the frontal cortex. Low [3H]-nicotine binding was
      observed in all layers of the frontal cortex in comparison to layers in the
      medial temporal gyrus, insular cortex and hippocampus. Immunohistochemical
      detection in the AD case revealed abundant glial fibrillary acidic protein
      positive (GFAP+) reactive astrocytes and alpha7 nAChR expressing GFAP+ astrocytes
      both in the vicinity and surrounding Abeta neuritic plaques in the FC and HIP.
      Although fewer Abeta plaques were observed in the HIP, some hippocampal GFAP+
      astrocytes contained Abeta-positive (6 F/3D) granules within their somata.
      CONCLUSIONS: Astrocytosis shows a distinct regional pattern in AD brain compared
      to fibrillar Abeta, suggesting that different types of astrocytes may be
      associated with the pathophysiological processes in AD.

PMID- 23880039
TI  - Preparation of porous bioceramics using reverse thermo-responsive hydrogels in
      combination with rhBMP-2 carriers: in vitro and in vivo evaluation.
AB  - Porous biphasic calcium phosphates (BCP) were fabricated using reverse thermo
      responsive hydrogels with hydroxyapatite (HAp) and beta-tricalcium (beta-TCP)
      powder and planetary centrifugal mixer. This hydrogel mixture slurry will shrink
      and compress the HAp powder during the sintering process. The porous bioceramics
      are expected to have good mechanical properties after sintering at 1200 degrees
      C. Reverse thermo-responsive hydrogels of poly[(N-isopropylacrylamide)-co
      (methacrylic acid)] p(NiPAAm-MAA) were synthesized by free-radical cross-linking
      copolymerization, and their chemical properties were evaluated by nuclear
      magnetic resonance spectroscopy, infrared spectroscopy, and electrospray
      ionization mass spectrometry. The lower critical solution temperature (LCST) of
      the hydrogel was determined using turbidity measurements. A thermogravimetric
      analysis was used to examine the thermal properties. The porous bioceramic
      properties were analyzed by X-ray diffraction, scanning electron microscopy, bulk
      density, compressive strength testing and cytotoxicity. The compressive strength
      and average porosity of the porous bioceramics were examined at approximately
      6.8MPa and 66% under 10wt% p(NiPAAm-MAA)=99:1 condition. The ratio of HAp/beta
      TCP can adjust two different compositional behaviors during the 1200 degrees C
      sintering process without resulting in cell toxicity. The (rhBMP-2)-HAp-PLGA
      carriers were fabricated as in our previous study of the double emulsion and drop
      coating technique. Results of animal study included histological micrographs of
      the 1-mm defect in the femurs, with the rhBMP-2 carrier group, the bioceramic
      spacer group and the bioceramic spacer with rhBMP-2 carriers group showing better
      callus formation around the femur defect site than the control group. The optimal
      dual effects of the bone growth factors from osteoconductive bioceramics and
      osteoinductive rhBMP-2 carriers produced better bone formation. 

PMID- 23880041
TI  - Suppression of translucent elongated structures: applications in chest
      radiography.
AB  - Projection images, such as those routinely acquired in radiological practice, are
      difficult to analyze because multiple 3-D structures superimpose at a single
      point in the 2-D image. Removal of particular superimposed structures may improve
      interpretation of these images, both by humans and by computers. This work
      therefore presents a general method to isolate and suppress structures in 2-D
      projection images. The focus is on elongated structures, which allows an
      intensity model of a structure of interest to be extracted using local
      information only. The model is created from profiles sampled perpendicular to the
      structure. Profiles containing other structures are detected and removed to
      reduce the influence on the model. Subspace filtering, using blind source
      separation techniques, is applied to separate the structure to be suppressed from
      other structures. By subtracting the modeled structure from the original image a
      structure suppressed image is created. The method is evaluated in four
      experiments. In the first experiment ribs are suppressed in 20 artificial
      radiographs simulated from 3-D lung computed tomography (CT) images. The proposed
      method with blind source separation and outlier detection shows superior
      suppression of ribs in simulated radiographs, compared to a simplified approach
      without these techniques. Additionally, the ability of three observers to
      discriminate between patches containing ribs and containing no ribs, as measured
      by the area under the receiver operating characteristic curve (AUC), reduced from
      0.99-1.00 on original images to 0.75-0.84 on suppressed images. In the second
      experiment clavicles are suppressed in 253 chest radiographs. The effect of
      suppression on clavicle visibility is evaluated using the clavicle contrast and
      border response, showing a reduction of 78% and 34%, respectively. In the third
      experiment nodules extracted from CT were simulated close to the clavicles in 100
      chest radiographs. It was found that after suppression contrast of the nodules
      was higher than of the clavicles (1.35 and 0.55, respectively) than on original
      images (1.83 and 2.46, respectively). In the fourth experiment catheters were
      suppressed in chest radiographs. The ability of three observers to discriminate
      between patches originating from 36 images with and 21 images without catheters,
      as measured by the AUC, reduced from 0.98-0.99 on original images to 0.64-0.74 on
      suppressed images. We conclude that the presented method can markedly reduce the
      visibility of elongated structures in chest radiographs and shows potential to
      enhance diagnosis. 

PMID- 23880040
TI  - Fast local trust region technique for diffusion tensor registration using exact
      reorientation and regularization.
AB  - Diffusion tensor imaging is widely used in brain connectivity research. As more
      and more studies recruit large numbers of subjects, it is important to design
      registration methods which are not only theoretically rigorous, but also
      computationally efficient. However, the requirement of reorienting diffusion
      tensors complicates and considerably slows down registration procedures, due to
      the correlated impacts of registration forces at adjacent voxel locations. Based
      on the diffeomorphic Demons algorithm (Vercauteren , 2009), we propose a fast
      local trust region algorithm for handling inseparable registration forces for
      quadratic energy functions. The method guarantees that, at any time and at any
      voxel location, the velocity is always within its local trust region. This local
      regularization allows efficient calculation of the transformation update with
      numeric integration instead of completely solving a large linear system at every
      iteration. It is able to incorporate exact reorientation and regularization into
      the velocity optimization, and preserve the linear complexity of the
      diffeomorphic Demons algorithm. In an experiment with 84 diffusion tensor images
      involving both pair-wise and group-wise registrations, the proposed algorithm
      achieves better registration in comparison with other methods solving large
      linear systems (Yeo , 2009). At the same time, this algorithm reduces the
      computation time and memory demand tenfold.

PMID- 23880042
TI  - Dr. Justus Lehmann: expanding the frontiers of physical medicine and
      rehabilitation.

PMID- 23880043
TI  - A late Y2K phenomenon: responding to the learning preferences of Generation Y-
      bridging the digital divide by improving generational dialogue.

PMID- 23880044
TI  - A Generation Yer's perspective on Generation Y learning.

PMID- 23880045
TI  - Comments from Gen X.

PMID- 23880046
TI  - A baby boomer's response.

PMID- 23880047
TI  - Analytical review: focus on fall screening assessments.
AB  - BACKGROUND: Falls and their associated injuries profoundly impact health
      outcomes, functional independence, and health care expenses, particularly for the
      ever-increasing elderly population. This systematic search and review assessed
      the current evidence for the role of fall screening assessments. OBJECTIVE: To
      review the current evidence for fall risk screening assessments in community
      dwelling (outpatient), inpatient medical and surgical wards, inpatient
      rehabilitation centers, and postrehabilitation outpatient settings. DATA SOURCES:
      MEDLINE and Embase (January 1980 to December 2012). STUDY SELECTION: Prospective
      validation studies of acute medical or surgical inpatients, acute rehabilitation
      inpatients, outpatients who completed acute inpatient rehabilitation, or
      community-dwelling elderly. DATA EXTRACTION: Sensitivity, specificity, positive
      predictive value, negative predictive value, receiver operating characteristics
      with area under the curve. RESULTS: We summarized key findings from 6 literature
      reviews. We then identified 31 articles: 12 studies in community setting, 13 in
      the acute medical inpatient or surgical inpatient setting, and 6 studies in the
      rehabilitation setting. Twenty-two studies not previously reviewed were included,
      and 9 studies previously reviewed were considered relevant and were included to
      allow comparison with data from the studies not previously reviewed. CONCLUSION:
      We recommend consideration of 7 assessment tools to be used in conjunction with
      overall clinical evaluation to assess falls risk: the Timed Up and Go Test with a
      cutoff of >12.34 seconds and Functional Gait Assessment among community-dwelling
      elderly; St Thomas Risk Assessment Tool in medical inpatients <65 years old and
      surgical inpatients; Hendrich fall risk model II in medical inpatients; 10-Minute
      Walk Test in patients in poststroke rehabilitation; and Berg Balance Scale or the
      Step Test in patients in poststroke rehabilitation who had fallen during their
      inpatient stay.

PMID- 23880048
TI  - When teams fumble: cancer rehabilitation and the problem of the "handoff".

PMID- 23880049
TI  - Phantom limb pain from spinal sarcoma: a case report.
AB  - Phantom limb pain is a frequent sequela of amputation. A high prevalence of
      residual limb pain and back pain also exists among amputees. We present a case of
      a new-onset severe phantom limb pain resulting from a metastatic spinal mass in
      an 81-year-old patient with a history of malignant sarcoma and an old hip
      disarticulation amputation. The metastatic lesion, upon imaging, was found to
      involve the L3 vertebra and caused moderate compression of the thecal sac on the
      right and severe right lateral recess stenosis. After the mass was resected, the
      patient's phantom limb pain resolved. Our case report demonstrates that spinal
      metastatic pathologies may be a cause of phantom limb pain and should be included
      in the differential diagnosis of new-onset phantom limb pain or a change in
      phantom limb pain. 

PMID- 23880050
TI  - Reply: To PMID 23399296.

PMID- 23880051
TI  - RE: A Simple technique to restore needle patency during percutaneous lavage and
      aspiration of calcific rotator cuff tendinopathy.

PMID- 23880052
TI  - Feasibility and reproducibility of systolic right ventricular strain measurement
      by speckle-tracking echocardiography in premature infants.
AB  - BACKGROUND: Right ventricular (RV) systolic function is an important prognostic
      determinant of cardiopulmonary pathologies in premature infants. Measurements of
      dominant RV longitudinal deformation are likely to provide a sensitive measure of
      RV function. An approach for image acquisition and postacquisition processing is
      needed for reliable and reproducible measurements of myocardial deformation by
      two-dimensional (2D) speckle-tracking echocardiography. The aims of this study
      were to determine the feasibility and reproducibility of 2D speckle-tracking
      echocardiographic measurement of RV peak global longitudinal strain (pGLS) and
      peak global longitudinal strain rate in premature infants and to establish
      methods for acquiring and analyzing strain. METHODS: The study was designed in
      two phases: (1) a training phase to develop methods of image acquisition and
      postprocessing in a cohort of 30 premature infants (born at 28 +/- 1 weeks) and
      (2) a study phase to prospectively test in a separate cohort of 50 premature
      infants (born at 27 +/- 1 weeks) if the methods improved the feasibility and
      reproducibility of RV pGLS and peak global longitudinal strain rate measurements
      to a clinically significant level, assessed using Bland-Altman analysis (bias,
      limits of agreement, coefficient of variation, and intraclass correlation
      coefficient). RESULTS: Strain imaging was feasible from 84% of the acquisitions
      using the methods developed for optimal speckle brightness and frame rate for RV
      focused image acquisition. There was high intraobserver (bias, 3%; 95% limits of
      agreement, -1.6 to +1.6; coefficient of variation, 2.7%; intraclass correlation
      coefficient, 0.97; P = .02) and interobserver (bias, 7%; 95% limits of agreement,
      -4.8 to +4.73; coefficient of variation, 3.9%; intraclass correlation
      coefficient, 0.93; P < .05) reproducibility, with excellent linear correlation
      between the two pGLS measurements (r = 0.97 [P < .01] and r = 0.93 [P < .05],
      respectively). CONCLUSIONS: This study demonstrates high clinical feasibility and
      reproducibility of RV pGLS and RV peak global longitudinal strain rate
      measurements by 2D speckle-tracking echocardiography in premature infants and
      offers methods for image acquisition and data analysis for systolic strain
      imaging that can provide a reliable assessment of global RV function.

PMID- 23880053
TI  - Changes in fetal left and right ventricular strain mechanics during normal
      pregnancy.
AB  - BACKGROUND: The aim of this study was to detect normal changes in fetal two
      dimensional speckle-tracking echocardiography-derived values for global and
      regional longitudinal left and right ventricular strain, strain rate, and time to
      peak (T2P) global strain during pregnancy. METHODS: Forty-four healthy fetuses
      were examined prospectively during the second-trimester and third-trimester
      ultrasound examinations (20-24 and 30-34 weeks, respectively). Clips with high
      frame rates (mean, 120 frames/sec) of two-dimensional (B-mode) grayscale images
      of apical or basal four-chamber views of both ventricles were used for offline
      analyses of global and regional walls and segments (basal, mid, and apical) of
      myocardial strain and strain rate as well as T2P global strain in the
      longitudinal direction. RESULTS: There were statistically significant decreases
      in global and regional strain of the right ventricle between the second and third
      trimesters. No statistically significant changes were observed in global and
      regional strain of the left ventricle. Global and regional strain rates of both
      ventricles decreased in a similar way during pregnancy. The mean T2P longitudinal
      left ventricular global strain (adjusted for heart rate) increased mildly during
      fetal life. Whereas T2P longitudinal strain of the left ventricle at 20 to 24
      weeks was statistically significantly shorter than that of the right ventricle,
      no difference in T2P longitudinal strain was found at 30 to 34 weeks of gestation
      between both ventricles. CONCLUSIONS: The establishment of these changes between
      the second-trimester and third-trimester two-dimensional speckle-tracking
      echocardiography-derived reference values is a mandatory prerequisite for its use
      in evaluating (pathologic) changes in both ventricular functions during
      pregnancy.

PMID- 23880054
TI  - Antibiotic and anti-inflammatory therapies for cystic fibrosis.
AB  - Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection
      and an unremitting inflammatory response, which are responsible for most of CF
      morbidity and mortality. The median expected survival has increased from <6 mo in
      1940 to >38 yr now. This dramatic improvement, although not great enough, is due
      to the development of therapies directed at secondary disease pathologies,
      especially antibiotics. The importance of developing treatments directed against
      the vigorous inflammatory response was realized in the 1990s. New therapies
      directed toward the basic defect are now visible on the horizon. However, the
      impact of these drugs on downstream pathological consequences is unknown. It is
      likely that antibiotics and anti-inflammatory drugs will remain an important part
      of the maintenance regimen for CF in the foreseeable future. Current and future
      antibiotic and anti-inflammatory therapies for CF are reviewed. 

PMID- 23880056
TI  - Effect of antioxidant treatment on spinal GABA neurons in a neuropathic pain
      model in the mouse.
AB  - One feature of neuropathic pain is a reduced spinal gamma-aminobutyric acid
      (GABA)-ergic inhibitory function. However, the mechanisms behind this attenuation
      remain to be elucidated. This study investigated the involvement of reactive
      oxygen species in the spinal GABA neuron loss and reduced GABA neuron
      excitability in spinal nerve ligation (SNL) model of neuropathic pain in mice.
      The importance of spinal GABAergic inhibition in neuropathic pain was tested by
      examining the effects of intrathecally administered GABA receptor agonists and
      antagonists in SNL and naive mice, respectively. The effects of SNL and
      antioxidant treatment on GABA neuron loss and functional changes were examined in
      transgenic GAD67-enhanced green fluorescent protein positive (EGFP+) mice. GABA
      receptor agonists transiently reversed mechanical hypersensitivity of the hind
      paw in SNL mice. On the other hand, GABA receptor antagonists made naive mice
      mechanically hypersensitive. Stereological analysis showed that the numbers of
      enhanced green fluorescent protein positive (EGFP+) GABA neurons were
      significantly decreased in the lateral superficial laminae (I-II) on the
      ipsilateral L5 spinal cord after SNL. Repeated antioxidant treatments
      significantly reduced the pain behaviors and prevented the reduction in EGFP+
      GABA neurons. The response rate of the tonic firing GABA neurons recorded from
      SNL mice increased with antioxidant treatment, whereas no change was seen in
      those recorded from naive mice, which suggested that oxidative stress impaired
      some spinal GABA neuron activity in the neuropathic pain condition. Together the
      data suggest that neuropathic pain, at least partially, is attributed to
      oxidative stress, which induces both a GABA neuron loss and dysfunction of
      surviving GABA neurons. 

PMID- 23880057
TI  - Combined anticoagulation and antiplatelet therapy for high-risk patients with
      atrial fibrillation: a systematic review.
AB  - BACKGROUND: Previous research suggests uncertainty whether or not there is any
      additional benefit in adding antiplatelet therapy (APT) to anticoagulation
      therapy (ACT) in patients with high-risk atrial fibrillation (AF) in terms of
      reduction in vascular events, including stroke. The existing guidelines
      acknowledge an increased risk of bleeding associated with such a strategy;
      however, there is no consensus on the treatment pathway. OBJECTIVES: To
      determine, by undertaking a systematic review, if the addition of APT to ACT is
      beneficial compared with ACT alone in patients with AF who are considered to be
      at high risk of thromboembolic events (TEs). DATA SOURCES: Data sources included
      bibliographic databases {the Cochrane Library [Cochrane Central Register of
      Controlled Trials (CENTRAL)], MEDLINE, MEDLINE In-Process and Other Non-Indexed
      Citations, EMBASE, ClinicalTrials.gov, National Institute for Health Research
      (NIHR) Clinical Research Network Portfolio, Current Controlled Trials (CCT) and
      the World Health Organization International Clinical Trials Registry Platform
      (WHO ICTRP)}, reference lists from identified systematic reviews and relevant
      studies, and contact with clinical experts. Searches were from inception to
      September 2010 and did not use language restrictions or study design filters.
      REVIEW METHODS: Studies of any design were included to evaluate clinical
      effectiveness, including randomised controlled trials (RCTs), non-randomised
      comparisons, cohort studies, case series or registries, longitudinal studies,
      systematic reviews and meta-analyses, and conference abstracts published after
      2008. Inclusion criteria consisted of a population with AF, at high-risk of TEs,
      aged >= 18 years, on combined ACT and APT compared with others on ACT alone or
      ACT plus placebo. Inclusion decisions, assessment of study quality and data
      extraction were undertaken using methods to minimise bias. RESULTS: Fifty-three
      publications were included, reporting five RCTs (11 publications), 18 non
      randomised comparisons (24 publications) and 18 publications that reported
      reviews, which added no further data. There was variation in the population,
      types and doses of ACT and APT, definitions of outcomes, and length of follow-up
      between the studies. There was a paucity of directly randomised high-quality
      RCTs, whereas non-randomised comparisons were found to have significant
      confounding factors. No studies looked at the effect of ACT plus APT compared
      with ACT alone on vascular events in patients with AF following acute coronary
      syndrome (ACS) or percutaneous coronary intervention. In most studies,
      significant differences in event rates were not seen between the patients on
      combined therapy compared with those on ACT alone for outcomes such as stroke
      (including haemorrhagic and ischaemic strokes), rates of transient ischaemic
      attacks, composite end points of stroke and systemic embolism (SE), SE alone,
      acute myocardial infarction, mortality (vascular or all cause) or bleeding
      events. There was conflicting evidence regarding rates of major adverse events
      consisting of composite end points, although event rates were generally low.
      LIMITATIONS: An attempt was made to identify all of the available evidence around
      the subject despite the dearth of directly randomised studies using a robust
      review methodology. There was a paucity of directly randomised evidence to
      undertake a meta-analysis for the merits of one technology over another. The
      selection criteria were kept necessarily broad with regard to the population,
      intervention and comparator in order to capture all relevant studies.
      CONCLUSIONS: This systematic review suggests that there is still insufficient
      evidence to advocate a clear benefit of the addition of APT to ACT compared with
      ACT alone in reducing the risk of vascular events in a population of patients at
      high risk of TEs resulting from AF. It is recommended that a definitive
      prospective RCT needs to be undertaken in a population at high risk of
      atherosclerotic coronary artery and other vascular events in addition to being at
      high risk of AF-mediated TEs. From the UK context, at the time of writing, any
      future trial should compare adjusted-dose warfarin [international normalised
      ratio (INR) 2.0-3.0] plus aspirin (75-325 mg) with adjusted-dose warfarin (INR
      2.0-3.0). However, given the emergence of newer anticoagulation agents
      (dabigatran, rivaroxaban and apixaban) this prioritisation may need to be
      revisited in the future to reflect current best clinical practice. FUNDING: The
      National Institute for Health Research Health Technology Assessment programme.

PMID- 23880055
TI  - Tolerance develops to the antiallodynic effects of the peripherally acting opioid
      loperamide hydrochloride in nerve-injured rats.
AB  - Peripherally acting opioids are potentially attractive drugs for the clinical
      management of certain chronic pain states due to the lack of centrally mediated
      adverse effects. However, it remains unclear whether tolerance develops to
      peripheral opioid analgesic effects under neuropathic pain conditions. We
      subjected rats to L5 spinal nerve ligation (SNL) and examined the analgesic
      effects of repetitive systemic and local administration of loperamide
      hydrochloride, a peripherally acting opioid agonist. We found that the inhibition
      of mechanical hypersensitivity, an important manifestation of neuropathic pain,
      by systemic loperamide (1.5mg/kg subcutaneously) decreased after repetitive drug
      treatment (tolerance-inducing dose: 0.75 to 6.0mg/kg subcutaneously). Similarly,
      repeated intraplantar injection of loperamide (150 MUg/50 MUL intraplantarly) and
      D-Ala(2)-MePhe(4)-Glyol(5) enkephalin (300 MUg/50 MUL), a highly selective mu
      opioid receptor (MOR) agonist, also resulted in decreased inhibition of
      mechanical hypersensitivity. Pretreatment with naltrexone hydrochloride (5mg/kg
      intraperitoneally) and MK-801 (0.2mg/kg intraperitoneally) attenuated systemic
      loperamide tolerance. Western blot analysis showed that repetitive systemic
      administration of morphine (3mg/kg subcutaneously), but not loperamide (3mg/kg
      subcutaneously) or saline, significantly increased MOR phosphorylation in the
      spinal cord of SNL rats. In cultured rat dorsal root ganglion neurons, loperamide
      dose-dependently inhibited KCl-induced increases in [Ca(2+)]i. However, this drug
      effect significantly decreased in cells pretreated with loperamide (3 MUM, 72
      hours). Intriguingly, in loperamide-tolerant cells, the delta-opioid receptor
      antagonist naltrindole restored loperamide's inhibition of KCl-elicited [Ca(2+)]i
      increase. Our findings indicate that animals with neuropathic pain may develop
      acute tolerance to the antiallodynic effects of peripherally acting opioids after
      repetitive systemic and local drug administration.

PMID- 23880058
TI  - Geodesics-based image registration: applications to biological and medical images
      depicting concentric ring patterns.
AB  - In many biological or medical applications, images that contain sequences of
      shapes are common. The existence of high inter-individual variability makes their
      interpretation complex. In this paper, we address the computer-assisted
      interpretation of such images and we investigate how we can remove or reduce
      these image variabilities. The proposed approach relies on the development of an
      efficient image registration technique. We first show the inadequacy of state-of
      the-art intensity-based and feature-based registration techniques for the
      considered image datasets. Then, we propose a robust variational method which
      benefits from the geometrical information present in this type of images. In the
      proposed non-rigid geodesics-based registration, the successive shapes are
      represented by a level-set representation, which we rely on to carry out the
      registration. The successive level sets are regarded as elements in a shape space
      and the corresponding matching is that of the optimal geodesic path. The proposed
      registration scheme is tested on synthetic and real images. The comparison
      against results of state-of-the-art methods proves the relevance of the proposed
      method for this type of images. 

PMID- 23880059
TI  - Obesity enhances nongenomic estrogen receptor crosstalk with the PI3K/Akt and
      MAPK pathways to promote in vitro measures of breast cancer progression.
AB  - INTRODUCTION: Epidemiological and clinical studies indicate that obesity is
      associated with a worse postmenopausal breast cancer prognosis and an increased
      risk of endocrine therapy resistance. However, the mechanisms mediating these
      effects remain poorly understood. Here we investigate the molecular pathways by
      which obesity-associated circulating factors in the blood enhance estrogen
      receptor alpha (ERalpha) positive breast cancer cell viability and growth.
      METHODS: Blood serum was collected from postmenopausal breast cancer patients and
      pooled by body mass index (BMI) category (Control: 18.5 to 24.9 kg/m2; Obese:
      >=30.0 kg/m2). The effects of patient sera on MCF-7 and T47D breast cancer cell
      viability and growth were examined by MTT and colony formation assays,
      respectively. Insulin-like growth factor receptor 1(IGF-1R), Akt, and ERK1/2
      activation and genomic ERalpha activity were assessed to determine their possible
      contribution to obese patient sera-induced cell viability and growth. To further
      define the relative contribution of these signaling pathways, cells grown in
      patient sera were treated with various combinations of ERalpha, PI3K/Akt and MAPK
      targeted therapies. Comparisons between cells exposed to different experimental
      conditions were made using one-way analysis of variance (ANOVA) and Student's t
      test. RESULTS: Cells grown in media supplemented with obese patient sera
      displayed greater cell viability and growth as well as IGF-1R, Akt and ERK1/2
      activation relative to control sera. Despite the lack of a significant difference
      in genomic ERalpha activity following growth in obese versus control patient
      sera, we observed a dramatic reduction in cell viability and growth after
      concurrent inhibition of the ERalpha and PI3K/Akt signaling pathways. Further, we
      demonstrated that ERalpha inhibition was sufficient to attenuate obese serum
      induced Akt and ERK1/2 activation. Together, these data suggest that obesity
      promotes greater ERalpha positive breast cancer cell viability and growth through
      enhanced crosstalk between nongenomic ERalpha signaling and the PI3K/Akt and MAPK
      pathways. CONCLUSIONS: Circulating factors in the serum of obese postmenopausal
      women stimulate ERalpha positive breast cancer cell viability and growth by
      facilitating non-genomic ERalpha crosstalk with the PI3K/Akt and MAPK signaling
      pathways. These findings provide valuable insight into one mechanism by which
      obesity may promote ERalpha positive postmenopausal breast cancer progression and
      endocrine therapy resistance.

PMID- 23880060
TI  - Cardiorespiratory performance and blood chemistry during swimming and recovery in
      three populations of elite swimmers: Adult sockeye salmon.
AB  - Every year, millions of adult sockeye salmon (Oncorhynchus nerka) perform an
      arduous, once-in-a-lifetime migration up the Fraser River (BC, Canada) to return
      to their natal stream to spawn. The changes in heart rate, stroke volume, and
      arterio-venous oxygen extraction (i.e., factors determining rates of oxygen
      delivery to the tissues by the cardiovascular system) have never been directly
      and simultaneously measured along with whole animal oxygen uptake in a maximally
      swimming fish. Here, such measurements were made using three sockeye salmon
      populations (Early Stuart, Chilko and Quesnel), which each performed two
      consecutive critical swimming speed (Ucrit) challenges to provide a comprehensive
      quantification of cardiovascular physiology, oxygen status and blood chemistry
      associated with swimming and recovery. Swim performance, oxygen uptake, cardiac
      output, heart rate and stroke volume did not significantly vary at rest, during
      swimming or during recovery between populations or sexes. Despite incomplete
      metabolic recovery between swim challenges, all fish repeated their swim
      performance and similar quantitative changes in the cardiorespiratory variables
      were observed for each swim challenge. The high maximum cardiorespiratory
      performance and excellent repeat swim performance are clearly beneficial in
      allowing the salmon to maintain steady ground speeds and reach the distant
      spawning grounds in a timely manner. 

PMID- 23880061
TI  - Does posture of the cervical spine influence dorsal neck muscle activity when
      lifting?
AB  - Previous studies have shown that postural orientations of the neck, such as
      flexed or forward head postures, are associated with heightened activity of the
      dorsal neck muscles. While these studies describe the impact of variations in
      neck posture alone, there is scant literature regarding the effect of neck
      posture on muscle activity when combined with upper limb activities such as
      lifting. The purpose of this study was to evaluate the effect of three different
      neck postures on the activity of the different layers of the dorsal neck muscles
      during a lifting task. Ultrasound measurements of dorsal neck muscle deformation
      were compared over two time points (rest, during lift) during a lifting task
      performed in three different neck postural conditions (neutral, flexed and
      forward head posture) in 21 healthy subjects. Data were analysed by post-process
      speckle tracking analysis. Results demonstrated significantly greater muscle
      deformation induced by flexed and forward head postures, compared to the neutral
      posture, for all dorsal neck muscles at rest (p<0.05). Significant condition by
      time interactions associated with the lift was observed for four out of the five
      dorsal muscles (p<0.02). These findings demonstrate that posture of the cervical
      spine influenced the level of muscle deformation not only at rest, but also when
      lifting. The findings of the study suggest that neck posture should be considered
      during the evaluation or design of lifting activities as it may contribute to
      excessive demands on dorsal neck muscles with potential detrimental consequences.

PMID- 23880063
TI  - Unusual sudden cardiac death from an anomalous left coronary artery from the
      right sinus of Valsalva.
AB  - A left coronary artery arising from the right sinus of Valsalva is a rare
      congenital coronary anomaly. We report a case of a 5-year-old boy with an
      anomalous left coronary artery from the right sinus of Valsalva whose presenting
      sign was cardiac arrest. There is no reported instance of a child <9 years of age
      without other congenital cardiac defects having died suddenly with this coronary
      anomaly. The transthoracic echocardiogram demonstrated normal origins of the
      coronary arteries, but on autopsy, an anomalous origin of the left main coronary
      artery from the right sinus of Valsalva was found. 

PMID- 23880064
TI  - Dementia in older English people seems to be declining.

PMID- 23880062
TI  - Autophagy and bacterial infection: an evolving arms race.
AB  - Autophagy is an important membrane transport pathway that is conserved among
      eukaryotic cells. Although first described as an intracellular catabolic pathway
      used to break down self-components, autophagy has been found to play an important
      role in the elimination of intracellular pathogens. A variety of host mechanisms
      exist for recognizing and targeting intracellular bacteria to autophagosomes.
      Several intracellular bacteria have evolved ways to manipulate, inhibit, or avoid
      autophagy in order to survive in the cell. Thus, the autophagy pathway can be
      viewed as an evolutionarily conserved host response to infection.

PMID- 23880065
TI  - The DNA damage response during mitosis.
AB  - Cells are equipped with a cell-intrinsic signaling network called the DNA damage
      response (DDR). This signaling network recognizes DNA lesions and initiates
      various downstream pathways to coordinate a cell cycle arrest with the repair of
      the damaged DNA. Alternatively, the DDR can mediate clearance of affected cells
      that are beyond repair through apoptosis or senescence. The DDR can be activated
      in response to DNA damage throughout the cell cycle, although the extent of DDR
      signaling is different in each cell cycle phase. Especially in response to DNA
      double strand breaks, only a very marginal response was observed during mitosis.
      Early on it was recognized that cells which are irradiated during mitosis
      continued division without repairing broken chromosomes. Although these initial
      observations indicated diminished DNA repair and lack of an acute DNA damage
      induced cell cycle arrest, insight into the mechanistic re-wiring of DDR
      signaling during mitosis was only recently provided. Different mechanisms appear
      to be at play to inactivate specific signaling axes of the DDR network in
      mitosis. Importantly, mitotic cells not simply inactivate the entire DDR, but
      appear to mark their DNA damage for repair after mitotic exit. Since the
      treatment of cancer frequently involves agents that induce DNA damage as well as
      agents that block mitotic progression, it is clinically relevant to obtain a
      better understanding of how cancer cells deal with DNA damage during interphase
      versus mitosis. In this review, the molecular details concerning DDR signaling
      during mitosis as well as the consequences of encountering DNA damage during
      mitosis for cellular fate are discussed. 

PMID- 23880066
TI  - A new co-ultramicronized composite including palmitoylethanolamide and luteolin
      to prevent neuroinflammation in spinal cord injury.
AB  - BACKGROUND: It has recently been demonstrated that palmitoylethanolamide (PEA),
      an endogenous lipid amide belonging to the N-acylethanolamine family, exerts
      neuroprotection in central nervous system (CNS) pathologies. In recent studies,
      we have demonstrated that treatment with PEA significantly reduced inflammatory
      secondary events associated with spinal cord injury (SCI). Since oxidative stress
      is considered to play an important role in neuroinflammatory disorders, in the
      present work we studied a new composite, a formulation including PEA and the
      antioxidant compound luteolin (Lut), subjected to an ultramicronization process,
      co-ultraPEALut. We investigated the effect of co-ultraPEALut (in the respective
      fixed doses of 10:1 in mass) in both an ex vivo organotypic spinal cord culture
      model and an in vivo model of SCI. METHODS: For the organotypic cultures, spinal
      cords were prepared from mice at postnatal day 6 and were cut into transverse
      slices of 400 MUm thickness to generate the lumbar organotypic slice cultures.
      After 7 days of culturing, the slices were mechanically injured onto the center
      of the slice and the co-ultraPEALut was applied at different concentrations
      (0.00009, 0.0009 and 0.009 g/l) 1 hour before damage. For in vivo studies, SCI
      was induced in mice through spinal cord compression by the application of
      vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy,
      and co-ultraPEALut (1 mg/kg ip) was administered at 1 and 6 hours after SCI. At
      24 hours after SCI, mice were sacrificed and the spinal cords were collected for
      further evaluation. Additional animals were treated similarly and sacrificed 10
      days after SCI. RESULTS: Pretreatment with co-ultraPEALut significantly reduced
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in
      a concentration-dependent manner, restored neuronal nitric oxide synthase (nNOS)
      expression at all three tested concentrations, and protected cells by cell death
      (MTT assay) in spinal cord organotypic cultures. Moreover, we demonstrated in
      vivo that co-ultraPEALut 1 mg/kg reduced the severity of trauma induced by
      compression and improved the motor activity evaluated at 10 days post-injury.
      CONCLUSION: The present study demonstrates that the protective effect of PEA on
      SCI-associated neuroinflammation could be improved by co-ultramicronization with
      Lut possibly due to its antioxidant properties.

PMID- 23880068
TI  - The role of natural killer cells in autoimmune liver disease: a comprehensive
      review.
AB  - Natural Killer (NK) cells are important players of the innate arm of the immune
      system and provide an early defense against pathogens and tumor-transformed
      cells. Peripheral blood NK (PB-NK) cells were first identified because of their
      ability to spontaneously kill tumor-cell targets in vitro without the need for
      specific antigen priming, which is the reason that they were named 'natural
      killer' cells. The characterization of NK cells in human tissues and body organs
      represented another important step forward to better understand their physiology
      and physiopathology. In this regard, many reports revealed over the past decade a
      differential anatomic distribution of NK cell subsets in several sites such as
      the intestine, lung, cervix, placenta and liver as well as in secondary lymphoid
      organs such as spleen, lymph nodes and tonsils. Among all these tissues, the
      liver is certainly unique as its parenchyma contains an unusually high number of
      infiltrating immune cells with 30-50% of total lymphocytes being NK cells. Given
      the constant liver intake of non-self antigens from the gastrointestinal tract
      via the portal vein, hepatic NK (H-NK) cells must retain a certain degree of
      tolerance in the context of their immune-surveillance against dangers to the
      host. Indeed, the breakdown of the tolerogenic state of the liver-associated
      immune system has been shown to induce autoimmunity. However, the role of NK
      cells during the course of autoimmune liver diseases is still being debated
      mainly because a complete characterization of H-NK cells normally resident in
      healthy human liver has not yet been fully disclosed. Furthermore, the
      differences in phenotype and functions between human and mouse H-NK cells often
      preclude translation of results obtained from murine models into experimental
      approaches to be performed in humans. Here, we provide an extensive
      characterization of the phenotype of H-NK cells physiologically resident in the
      human liver by both mentioning data available in literature and including a set
      of original results recently developed in our laboratory. We then review our
      current knowledge in regard to the contribution of H-NK cells in regulating local
      immune homeostasis and tolerance as well as in inducing the development of liver
      autoimmunity. 

PMID- 23880067
TI  - Genomics of lymphoid malignancies reveal major activation pathways in
      lymphocytes.
AB  - Breakdown of tolerance leads to autoimmunity due to emergence of autoreactive T
      or B cell clones. Autoimmune diseases predispose to lymphoid malignancies and
      lymphoid malignancies, conversely, can manifest as autoimmune diseases. While it
      has been clear for a long time that a competitive advantage and uncontrolled
      growth of lymphocytes contribute to the pathogenesis of both lymphoid
      malignancies as well as autoimmune diseases, the overlap of the underlying
      mechanisms has been less well described. Next generation sequencing has led to
      massive expansion of the available genomic data in many diseases over the last
      five years. These data allow for comparison of the molecular pathogenesis between
      autoimmune diseases and lymphoid malignancies. Here, we review the similarities
      between autoimmune diseases and lymphoid malignancies: 1) Both, autoimmune
      diseases and lymphoid malignancies are characterized by activation of the same T
      and B cell signaling pathways, and dysregulation of these pathways can occur
      through genetic or epigenetic events. 2) In both scenarios, clonal and subclonal
      evolution of lymphocytes contribute to disease. 3) Development of both diseases
      not only depends on T or B cell intrinsic factors, such as germline or somatic
      mutations, but also on environmental factors. These include infections, the
      presence of other immune cells in the microenvironment, and the cytokine milieu.
      A better mechanistic understanding of the parallels between lymphomagenesis and
      autoimmunity may help the development of precision treatment strategies with
      rationally designed therapeutic agents. 

PMID- 23880069
TI  - Hypoxia inducible NOD2 interacts with 3-O-sulfogalactoceramide and regulates
      vesicular homeostasis.
AB  - BACKGROUND: Oxygen sensing in mammalian cells is a conserved signaling pathway
      regulated by hypoxia inducible factor type 1 (HIF-1). Inadequate oxygen supply
      (hypoxia) is common to many pathological disorders where autophagy plays an
      import role. The aim of this study was the identification and characterization of
      novel HIF-1 target genes that promote autophagy during hypoxia. METHODS: Whole
      genome Chromatin Immune Precipitation from hypoxic HeLa cells was used to
      identify novel HIF-1 target genes. Hypoxia induced expression and transcription
      regulation was studied in wild type and HIF-deficient cells. siRNA silencing of
      candidate genes was used to establish their role during autophagy. Recombinant
      protein was used for screening immobilized glycosylated lipids to identify
      potential ligands. RESULTS: We identified the Nucleotide Oligomerization Domain 2
      (NOD2/CARD15) as a novel HIF-1 target and 3-O-sulfo-galactoceramide (sulfatide)
      and Mycobacterium sp. specific sulfolipid-1 as the first NOD2 ligands that both
      compete for binding to NOD2. Loss of NOD2 function impaired autophagy upstream of
      the autophagy inhibitor chloroquine by reducing the number of acidic vesicles.
      Inhibition of sulfatide synthesis elicited defects in autophagy similar to the
      NOD2 loss of function but did not influence NOD2-mediated NF-kB signaling.
      CONCLUSIONS: Our findings suggest that the interaction of NOD2 with sulfatide may
      mediate the balance between autophagy and inflammation in hypoxic cells. GENERAL
      SIGNIFICANCE: These findings may lead to a better understanding of complex
      inflammatory pathologies like Crohn's disease and tuberculosis where both NOD2
      and hypoxia are implicated.

PMID- 23880070
TI  - The role of positive charges on G-quadruplex binding small molecules: learning
      from bisaryldiketene derivatives.
AB  - BACKGROUND: G-quadruplexes are promising therapeutic targets for small molecules.
      In general, the introduction of steady positive charges through the in situ
      alkylation of nitrogen atoms within potential G-quadruplex ligands can
      significantly improve their quadruplex binding and stabilization abilities.
      However, our previous studies on bisaryldiketene derivatives showed that the
      derivative M4, whose central piperidone moiety is quaternized, exhibits a poor G
      quadruplex stabilization ability. METHODS: To clarify this unusual finding, CD,
      ITC, UV and NMR analyses were performed to determine the binding behaviors of M4
      and its non-quaternized analog M2 to G-quadruplex DNA [d(TGGGT)]4. Molecular
      modeling approaches were also employed to help illustrate ligand-quadruplex DNA
      interactions. RESULTS: The CD melting and ITC analyses revealed that M2 exhibited
      much stronger stabilization and binding abilities to [d(TGGGT)]4 compared to M4.
      Moreover, the CD and ITC analyses in combination with UV, NMR and MD simulations
      revealed that M2 tended to be end-stacked on the G-quartet, whereas M4 tended to
      be bound in the groove region. Analysis of the electrostatic potential showed
      that the charged surface of M4 was more positive than that of M2 and other
      reported ligands that bind to the G-quadruplex via end-stacking interactions.
      CONCLUSIONS: The results indicated that the different positively charged surfaces
      of M2 and M4 might be the key reason for their different binding modes. These
      different binding modes also lead to different binding affinities and
      stabilization abilities for [d(TGGGT)]4. GENERAL SIGNIFICANCE: These results
      provide new clues for the rational design of G-quadruplex-binding small molecules
      with steady positive charges.

PMID- 23880071
TI  - Simple frailty score predicts postoperative complications across surgical
      specialties.
AB  - BACKGROUND: Our purpose was to determine the relationship between preoperative
      frailty and the occurrence of postoperative complications after colorectal and
      cardiac operations. METHODS: Patients 65 years or older undergoing elective
      colorectal or cardiac surgery were enrolled. Seven baseline frailty traits were
      measured preoperatively: Katz score less than or equal to 5, Timed Up and Go test
      greater than or equal to 15 seconds, Charlson Index greater than or equal to 3,
      anemia less than 35%, Mini-Cog score less than or equal to 3, albumin less than
      3.4 g/dL, and 1 or more falls within 6 months. Patients were categorized by the
      number of positive traits as follows: nonfrail: 0 to 1 traits, prefrail: 2 to 3
      traits, and frail: 4 or more traits. RESULTS: Two hundred one subjects (age 74 +/
      6 years) were studied. Preoperative frailty was associated with increased
      postoperative complications after colorectal (nonfrail: 21%, prefrail: 40%,
      frail: 58%; P = .016) and cardiac operations (nonfrail: 17%, prefrail: 28%,
      frail: 56%; P < .001). This finding in both groups was independent of advancing
      age. Frail individuals in both groups had longer hospital stays and higher 30-day
      readmission rates. Receiver operating characteristic curves examining frailty's
      ability to forecast complications were colorectal (.702, P = .004) and cardiac
      (.711, P < .001). CONCLUSIONS: A simple preoperative frailty score defines older
      adults at higher risk for postoperative complications across surgical
      specialties.

PMID- 23880073
TI  - Idiopathic ankylosis-resorption: diagnosis and treatment.
AB  - Dental ankylosis involves the fusion of root to bone. The idiopathic form occurs
      spontaneously before the eruption of the tooth concerned. Etiology is unknown. As
      the tooth becomes part of the bone-remodeling process, it is gradually resorbed
      and is replaced by bony tissue. The process is quite rapid and weakens the tooth.
      Thus, early diagnosis makes it possible to perform a graft in optimal conditions,
      this being the only means of severing the ankylosis and achieving adequate
      eruption. In some rare cases, the ankylotic point of fusion can be reached
      surgically and can be eliminated before orthodontic traction is initiated. 

PMID- 23880072
TI  - Systematic reviews and meta-analyses of home telemonitoring interventions for
      patients with chronic diseases: a critical assessment of their methodological
      quality.
AB  - BACKGROUND: Systematic reviews and meta-analyses of home telemonitoring
      interventions for patients with chronic diseases have increased over the past
      decade and become increasingly important to a wide range of clinicians, policy
      makers, and other health care stakeholders. While a few criticisms about their
      methodological rigor and synthesis approaches have recently appeared, no formal
      appraisal of their quality has been conducted yet. OBJECTIVE: The primary aim of
      this critical review was to evaluate the methodology, quality, and reporting
      characteristics of prior reviews that have investigated the effects of home
      telemonitoring interventions in the context of chronic diseases. METHODS: Ovid
      MEDLINE, the Database of Abstract of Reviews of Effects (DARE), and Health
      Technology Assessment Database (HTA) of the Cochrane Library were electronically
      searched to find relevant systematic reviews, published between January 1966 and
      December 2012. Potential reviews were screened and assessed for inclusion
      independently by three reviewers. Data pertaining to the methods used were
      extracted from each included review and examined for accuracy by two reviewers. A
      validated quality assessment instrument, R-AMSTAR, was used as a framework to
      guide the assessment process. RESULTS: Twenty-four reviews, nine of which were
      meta-analyses, were identified from more than 200 citations. The bibliographic
      search revealed that the number of published reviews has increased substantially
      over the years in this area and although most reviews focus on studying the
      effects of home telemonitoring on patients with congestive heart failure,
      researcher interest has extended to other chronic diseases as well, such as
      diabetes, hypertension, chronic obstructive pulmonary disease, and asthma.
      Nevertheless, an important number of these reviews appear to lack optimal
      scientific rigor due to intrinsic methodological issues. Also, the overall
      quality of reviews does not appear to have improved over time. While several
      criteria were met satisfactorily by either all or nearly all reviews, such as the
      establishment of an a priori design with inclusion and exclusion criteria, use of
      electronic searches on multiple databases, and reporting of studies
      characteristics, there were other important areas that needed improvement.
      Duplicate data extraction, manual searches of highly relevant journals, inclusion
      of gray and non-English literature, assessment of the methodological quality of
      included studies and quality of evidence were key methodological procedures that
      were performed infrequently. Furthermore, certain methodological limitations
      identified in the synthesis of study results have affected the results and
      conclusions of some reviews. CONCLUSIONS: Despite the availability of
      methodological guidelines that can be utilized to guide the proper conduct of
      systematic reviews and meta-analyses and eliminate potential risks of bias, this
      knowledge has not yet been fully integrated in the area of home telemonitoring.
      Further efforts should be made to improve the design, conduct, reporting, and
      publication of systematic reviews and meta-analyses in this area.

PMID- 23880075
TI  - European College of Orthodontics: Commission of Affiliation and Titularisation.
AB  - Date of birth: 10/12/1993; gender: female. A PRETREATMENT RECORDS: (3/2008; 14.3
      yrs). DIAGNOSIS: Class III. B POST-TREATMENT RECORDS: (12/2009; 15.11 yrs).
      RETENTION: Intercanine wires bonded on both arches. C POST-RETENTION RECORDS:
      (12/2010; 16.11 yrs).

PMID- 23880078
TI  - European College of Orthodontics: Commission of Affiliation and Titularisation.
AB  - Date of birth: 15/1/1994; gender: male. A PRETREATMENT RECORDS: (18/3/2008; 13 y
      10 m). DIAGNOSIS: Skeletal Class II due to mandibular retrognathism. Agenesia of
      12 and 22. Deep bite due to upper and lower alveolar retrusion. TREATMENT:
      Leveling of arches using passive self-ligating .022 *.028" multibracket appliance
      (Damon) with reopening of spaces at 12 and 22. Class II mechanics. Finishing with
      pre-implant check-up. Retention and temporary stage before implants at 12 and 22.
      B POST-TREATMENT RECORDS: (19/04/2010; 15 y 11 m). RETENTION: Wire bonded
      lingually from 33 to 43. Rigid maxillary thermoformed plate for night time.
      Daytime maxillary plate with prosthetic 11-22. C POST-RETENTION RECORDS:
      (27/03/2012; 17 y 11 m). D CLINICAL OBSERVATIONS: Inadequate control of the axis
      of 21 (to be corrected after implant placement).

PMID- 23880079
TI  - Eyelid contour detection and tracking for startle research related eye-blink
      measurements from high-speed video records.
AB  - Using the positions of the eyelids is an effective and contact-free way for the
      measurement of startle induced eye-blinks, which plays an important role in human
      psychophysiological research. To the best of our knowledge, no methods for an
      efficient detection and tracking of the exact eyelid contours in image sequences
      captured at high-speed exist that are conveniently usable by psychophysiological
      researchers. In this publication a semi-automatic model-based eyelid contour
      detection and tracking algorithm for the analysis of high-speed video recordings
      from an eye tracker is presented. As a large number of images have been acquired
      prior to method development it was important that our technique is able to deal
      with images that are recorded without any special parametrisation of the eye
      tracker. The method entails pupil detection, specular reflection removal and
      makes use of dynamic model adaption. In a proof-of-concept study we could achieve
      a correct detection rate of 90.6%. With this approach, we provide a feasible
      method to accurately assess eye-blinks from high-speed video recordings. 

PMID- 23880080
TI  - What are the costs and benefits of patient notification exercises following poor
      infection control practices in dentistry?
AB  - BACKGROUND: Allegations of serious failures in infection control practice were
      made against a dentist practicing in the South West of England. The dentist (who
      tested negative for Blood Borne Viruses (BBVs)) was immediately suspended.
      METHODS: Because inadequate infection control presents a potential risk of
      transmitting BBVs between patients, a notification exercise was undertaken. Of
      7625 patients contacted, 2780 (37%) were tested. RESULTS: Nine cases of Hepatitis
      B (HBV) and four cases of Hepatitis C (HCV) were identified, of which seven were
      previously diagnosed. None of these were children. All of the six newly diagnosed
      cases had recognized risk factors for BBVs. The costs of the notification
      exercise were estimated at L311,500 of which L165,000 was staff costs, (L51,916
      per newly diagnosed case). CONCLUSION: This study did not demonstrate any patient
      to-patient transmission of blood-borne viruses but the response rate was
      relatively low. There are significant costs associated with undertaking
      notification exercises. These findings should inform future recommendations and
      practice in this area.

PMID- 23880081
TI  - Rapid modifications of N-substitution in iminosugars: development of new beta
      glucocerebrosidase inhibitors and pharmacological chaperones for Gaucher disease.
AB  - The rapid discovery of beta-glucocerebrosidase (GCase) inhibitors and
      pharmacological chaperones for Gaucher disease is described. The N-aminobutyl DNJ
      based iminosugar was synthesized and conjugating with a variety of carboxylic
      acids to generate a N-diversely substituted iminosugar-based library. Several
      members of this library were found to be nanomolar-range inhibitors of GCase; the
      inhibition constant Ki of the most potent was found to be 71nM. Although these
      new molecules showed reasonable chaperoning activity (1.5- to 1.9-fold) in the
      N370S fibroblast of Gaucher patient-derived cell line, this was accompanies by a
      concomitant decrease in the cellular alpha-glucosidase activity, which might
      limit their further therapeutic potential. Next, newly developed N-substituents
      were assembled with pyrrolidine-based scaffolds to generate new molecules for
      further evaluation. The new 2,5-dideoxy-2,5-imino-d-mannitol (DMDP)-based
      iminosugar 22 was found to exhibit a satisfactory chaperoning activity to enhance
      GCase activity by 2.2-fold in Gaucher N370S cell line, without impairment of
      cellular alpha-glucosidase activity. 

PMID- 23880083
TI  - Exploring pyrimidine-substituted curcumin analogues: design, synthesis and
      effects on EGFR signaling.
AB  - Epidermal growth factor receptor (EGFR) is an effective molecular target of anti
      cancer therapies. Curcumin inhibits cancer cell growth in vitro by suppressing
      gene expression of EGFR and reduces tumor growth in various animal models. To
      overcome instable and insoluble properties of curcumin as therapeutics, we
      designed and synthesized six novel pyrimidine-substituted curcumin analogues with
      or without a hydroxyl group originally present in curcumin. The cell viability
      tests indicated that IC50 of the analogues containing hydroxyl group were 3 to 8
      fold lower than those of the analogues without hydroxyl group in two colon cancer
      cell lines tested. Western blot analysis indicates the analogues containing
      hydroxyl group inhibited expression and tyrosine phosphorylation of EGFR. Further
      protein analyses showed that the analogues had anti-cellular proliferation, pro
      apoptosis, and cell cycle arrest properties associated with suppressed EGFR
      expression. These results indicate that the hydroxyl groups in curcumin and the
      analogues were critical for observed biological activities. 

PMID- 23880082
TI  - Antiprotozoal activity of bicyclic diamines with a N-methylpiperazinyl group at
      the bridgehead atom.
AB  - omega-Aminoacyl and -alkyl derivatives of 4-(4-methylpiperazin-1
      yl)bicyclo[2.2.2]octan-2-amines and of 5-(4-methylpiperazin-1-yl)-2
      azabicyclo[3.2.2]nonanes were prepared and their activities were examined in
      vitro against the multiresistant K1 strain of Plasmodium falciparum and against
      Trypanosoma brucei rhodesiense (STIB 900). Some of the newly synthesized
      compounds showed very promising antiprotozoal activity and selectivity. A few of
      the alkylamino-2-azabicyclo[3.2.2]nonanes exhibited high antiplasmodial activity,
      whereas a single bicyclo[2.2.2]octane derivative was the most potent
      antitrypanosomal compound. The results of the newly synthesized compounds were
      compared with the activities of already synthesized compounds and of drugs in
      use. Structure-activity relationships were discussed. 

PMID- 23880086
TI  - FiloDetect: automatic detection of filopodia from fluorescence microscopy images.
AB  - BACKGROUND: Filopodia are small cellular projections that help cells to move
      through and sense their environment. Filopodia play crucial roles in processes
      such as development and wound-healing. Also, increases in filopodia number or
      size are characteristic of many invasive cancers and are correlated with
      increased rates of metastasis in mouse experiments. Thus, one possible route to
      developing anti-metastatic therapies is to target factors that influence the
      filopodia system. Filopodia can be detected by eye using confocal fluorescence
      microscopy, and they can be manually annotated in images to quantify filopodia
      parameters. Although this approach is accurate, it is slow, tedious and not
      entirely objective. Manual detection is a significant barrier to the discovery
      and quantification of new factors that influence the filopodia system. RESULTS:
      Here, we present FiloDetect, an automated tool for detecting, counting and
      measuring the length of filopodia in fluorescence microscopy images. The method
      first segments the cell from the background, using a modified triangle threshold
      method, and then extracts the filopodia using a series of morphological
      operations. We verified the accuracy of FiloDetect on Rat2 and B16F1 cell images
      from three different labs, showing that per-cell filopodia counts and length
      estimates are highly correlated with the manual annotations. We then used
      FiloDetect to assess the role of a lipid kinase on filopodia production in breast
      cancer cells. Experimental results show that PI4KIII beta expression leads to an
      increase in filopodia number and length, suggesting that PI4KIII beta is involved
      in driving filopodia production. CONCLUSION: FiloDetect provides accurate and
      objective quantification of filopodia in microscopy images, and will enable large
      scale comparative studies to assess the effects of different genetic and chemical
      perturbations on filopodia production in different cell types, including cancer
      cell lines.

PMID- 23880087
TI  - The influence of vitamin E succinate on the stability of polyethylene oxide PEO
      controlled release matrix tablets.
AB  - Hydrophilic matrices are a principal technology used for extended release (ER)
      oral dosage forms and a recent review concluded that their development is
      currently one of the most important challenges in pharmaceutical research. High
      molecular weight polyethylene oxides (PEOs) have been proposed as an alternative
      to hydroxypropylmethylcellulose (HPMC) for the manufacture of controlled release
      matrix tablets. It is known that PEO's are prone to oxidative degradation which
      can occur by chain scission and can be catalyzed by metal ions. In this study, we
      investigated the stability of PEO matrix tablets, of different molecular weight,
      containing diltiazem hydrochloride, when stored at 40  degrees C. The results
      show that there were dramatic increases in the release rate of the diltiazem
      following storage over only a few weeks, resulting in immediate release profiles
      after eight weeks, even for the highest molecular weight grade. We employed Gel
      permeation chromatography (GPC), viscosity and differential scanning calorimetry
      (DSC) techniques to try and determine the underlying causes of these dramatic
      shifts in dissolution profiles on storage. The results showed that there were
      significant decreases in the molecular weight of the PEO's during storage. The
      second part of the study looked at the addition of three different levels of
      vitamin E succinate to the tablets. The results clearly demonstrate the ability
      of the added antioxidant to reverse the significant reductions in molecular
      weight seen using GPC, viscosity and DSC. Importantly the addition of the
      antioxidant was able to stabilize the release profile of the diltiazem especially
      when present at a 1% level. Researchers and those working in pharmaceutical
      development should be aware of the potential stability risks when making matrix
      tablets containing PEO's and may wish to consider the addition of an antioxidant
      to the tablet formulation.

PMID- 23880088
TI  - Hemocompatibility study of a bacterial cellulose/polyvinyl alcohol nanocomposite.
AB  - Bacterial cellulose (BC) has been suggested to be a suitable biomaterial for the
      development of cardiovascular grafts. The combination of BC with polyvinyl
      alcohol (PVA) results in nanocomposites with improved properties. Surprisingly,
      there are very few studies on the BC-blood interaction. This is the focus of this
      paper. We present the first thorough assessment of the hemocompatibility of the
      BC/PVA nanocomposite. Whole blood clotting time, plasma recalcification, Factor
      XII activation, platelet adhesion and activation, hemolytic index and complement
      activation are all determined. The platelet activation profiles on BC and BC/PVA
      surfaces are comprehensively characterized. BC and BC/PVA outperformed ePTFE-
      used as a point of comparison--thus evidencing their suitability for
      cardiovascular applications.

PMID- 23880084
TI  - Cardiac index and oxygen delivery during low and high tidal volume ventilation
      strategies in patients with acute respiratory distress syndrome: a crossover
      randomized clinical trial.
AB  - INTRODUCTION: The beneficial effect of low tidal volume (TV) ventilation strategy
      on mortality in patients with acute respiratory distress syndrome (ARDS) has been
      attributed to the protective effect on ventilator-induced lung injury, and yet
      its effect on cardiovascular function might also play an important role. The aim
      of this study was to assess whether low TV ventilation improves cardiac output
      and oxygen delivery compared with high TV ventilation strategy in patients with
      ARDS. METHODS: In this crossover randomized clinical trial 16 ARDS patients were
      recruited in an intensive care unit at a university-affiliated hospital. Each
      patient was ventilated for 30 min with low (6 mL/kg) and 30 min with high (12
      mL/kg) TV. The two experimental periods, applied in random order and with
      allocation concealment, were separated by 30 min of basal ventilation. Minute
      ventilation was constantly maintained by appropriate respiratory rate changes.
      RESULTS: Compared with high TV ventilation, low TV ventilation showed decreased
      pH (7.37 vs. 7.41, P = 0.001) and increased PaCO2 (49 vs. 43 mmHg; P = 0.002).
      Cardiac index and oxygen delivery index were increased with low compared with
      high TV ventilation (3.9 vs. 3.5 L.min-1.m-2, P = 0.012, and 521 vs. 463 mL.min
      1.m-2, P = 0.002, respectively), while oxygen extraction ratio decreased (0.36
      vs. 0.44, P = 0.027). In four patients oxygen extraction ratio was >0.5 during
      high TV but not during low TV strategy. The magnitude of the change in cardiac
      index was positively associated with PaCO2 variation (P = 0.004), while it was
      unrelated to the magnitude of changes in TV and airway pressure. The decrease of
      cardiac index was predicted by PaCO2 reduction, with and area under ROC curve of
      0.72. CONCLUSIONS: Our findings suggest that a low TV ventilation strategy
      increases cardiac index and oxygen delivery, thus supporting the hypothesis that
      the beneficial effect of low TV ventilation in patients with ARDS could be
      partially explained by hemodynamic improvement. In other words, low tidal volume
      ventilation could be protective also for the cardiovascular system and not only
      for the lung. The slight increase of PaCO2 during low TV ventilation seems to
      predict the increase of cardiac index. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT00713713.

PMID- 23880089
TI  - Antimicrobial wool, polyester and a wool/polyester blend created by silver
      particles embedded in a silica matrix.
AB  - A two-step antimicrobial finishing procedure was applied to wool (WO) and
      polyester (PES) fabrics and a WO/PES fabric blend, in which the pad-dry-cure
      method was performed to create a functional silica matrix through the application
      of an inorganic-organic hybrid sol-gel precursor (RB) followed by the in situ
      synthesis of AgCl particles on the RB-treated fibres using 0.10 and 0.50mM AgNO3
      and NaCl. The bulk concentration of Ag on the cotton fibres was determined by
      inductively coupled plasma mass spectroscopy. The antimicrobial activity was
      determined for the bacteria Escherichia coli and Staphylococcus aureus, and the
      fungus Aspergillus niger. The results showed that the highest concentration of
      the adsorbed Ag compound particles was on the WO samples followed by the WO/PES
      and PES samples. The antimicrobial activity of the finished fabric samples
      strongly depended not only on the amount of adsorbed Ag but also on the
      properties of the fabric samples. Whereas Ag biocidal activity was generated for
      the finished PES samples at Ag particle concentrations of less than 10mg/kg, the
      34-times higher Ag particle concentration on the WO samples was insufficient to
      impart satisfactory antimicrobial activity because Ag chemically binds to the
      thiol groups on wool. The presence of wool fibres in WO/PES samples decreased the
      antimicrobial protection of the fabric blend compared with that of the PES
      fabric. A lethal concentration of adsorbed Ag compound particles for bacteria and
      fungi was produced only through the treatment of the WO and WO/PES samples with
      0.5mM AgNO3. 

PMID- 23880085
TI  - Generation of protection against Francisella novicida in mice depends on the
      pathogenicity protein PdpA, but not PdpC or PdpD.
AB  - Previous results suggest that mutations in most genes in the Francisella
      pathogenicity island (FPI) attenuate the bacterium. Using a mouse model, here we
      determined the impact of mutations in pdpA, pdpC, and pdpD in Francisella
      novicida on in vitro replication in macrophages, and in vivo immunogenicity. In
      contrast to most FPI genes, deletion of pdpC (FnDeltapdpC) and pdpD (FnDeltapdpD)
      from F. novicida did not impact growth in mouse bone-marrow derived macrophages.
      Nonetheless, both FnDeltapdpC and FnDeltapdpD were highly attenuated when
      administered intradermally. Infected mice produced relatively normal anti-F.
      novicida serum antibodies. Further, splenocytes from infected mice controlled
      intramacrophage Francisella replication, indicating T cell priming, and mice
      immunized by infection with FnDeltapdpC or FnDeltapdpD survived secondary lethal
      parenteral challenge with either F. novicida or Francisella tularensis LVS. In
      contrast, deletion of pdpA (FnDeltapdpA) ablated growth in macrophages in vitro.
      FnDeltapdpA disseminated and replicated poorly in infected mice, accompanied by
      development of some anti-F. novicida serum antibodies. However, primed Th1 cells
      were not detected, and vaccinated mice did not survive even low dose challenge
      with either F. novicida or LVS. Taken together, these results suggest that
      successful priming of Th1 cells, and protection against lethal challenge, depends
      on expression of PdpA. 

PMID- 23880090
TI  - Involvement of the alpha7-nicotinic acetylcholine receptors in the anti
      inflammatory action of the thymulin-related peptide (PAT).
AB  - BACKGROUND AND PURPOSE: Peptide analog of thymulin (PAT) has been shown to have
      anti-hyperalgesic and anti-inflammatory properties in animal models of
      inflammation. Recent reports suggest that the peripheral cholinergic system has
      an anti-inflammatory role mediated by alpha7-nicotinic acetylcholine receptor
      (alpha7-nAChR). Our aim is to investigate whether the action of PAT is mediated,
      via the cholinergic pathway. EXPERIMENTAL APPROACH: The anti-hyperalgesic and
      anti-inflammatory action of PAT was assessed in rat models of inflammatory
      nociceptive hyperactivity (carrageenan and endotoxin) and in a mice air-pouch
      model for localized inflammation, respectively; the possible attenuation of PAT's
      effects by pretreatment with the alpha7-nAchR specific antagonist
      methyllycaconitine citrate (MLA) was also investigated. In another series of
      experiments, using two electrode recordings, the effect of PAT on the alpha7
      nAChRs, expressed in Xenopus Oocytes, was also determined. KEY RESULTS:
      Administration of PAT reversed inflammatory nociceptive hyperactivity and cold
      and tactile hyperactivity in rats. This effect was partially or totally prevented
      by MLA, as assessed by different behavioral pain tests. Treatment with PAT also
      reduced the alteration of cytokines and NGF levels by carrageenan injection in
      the mouse air pouch model; this effect was partially antagonized by MLA.
      Electrophysiological recording demonstrated that PAT significantly potentiated
      the alpha7-nAchR expressed in Xenopus Oocytes. These effects were not observed
      when a control peptide, with a reverse sequence (rPAT), was utilized. CONCLUSIONS
      AND IMPLICATIONS: The behavioral and electrophysiological observations described
      in this report demonstrate that PAT mediates, at least partially, its anti
      inflammatory action by potentiating the alpha7-nAChR. These results indicate that
      PAT has a potential for new therapeutic applications as anti-inflammatory and
      analgesic agent.

PMID- 23880091
TI  - Prospective study on burns treated with Integra(r), a cellulose sponge and split
      thickness skin graft: comparative clinical and histological study--randomized
      controlled trial.
AB  - BACKGROUND: The aim of this study was to compare three different methods to cover
      excised burn wounds in a randomized controlled trial. METHODS: Fascially excised
      burn wounds, measuring 10 cm * 5 cm, were covered with Integra((r)), split
      thickness skin graft (STSG), and a viscose cellulose sponge CellonexTM in each of
      ten adult patients. Integra((r)) and CellonexTM treated areas were covered with
      thin STSG on day 14. Biopsies were taken 3, 7, 14, and 21 days, 3 months, and 12
      months after surgery, and samples were subjected to a range of
      immunohistochemical stains, in addition to hematoxylin and eosin (HE). Scar
      assessment was performed 3 and 12 months post-operatively with the Vancouver Scar
      Scale (VSS). RESULTS: Inflammation was not substantial in any of the study areas,
      but CellonexTM had the most neutrophils, histiocytes, and lymphocytes with
      significant differences on days 7 and 14. Complete vascularization of
      Integra((r)) seemed to occur later compared to the other materials. STSG had the
      most myofibroblasts on day 14 (p = 0.012). In VSS the quality of the scar
      improved in all materials from 3 to 12 months. CONCLUSIONS: The final results for
      all treatments after 12 months demonstrate equal clinical appearance, as well as
      histological and immunohistochemical findings.

PMID- 23880092
TI  - Inhibition of astroglial NF-kappaB enhances oligodendrogenesis following spinal
      cord injury.
AB  - BACKGROUND: Astrocytes are taking the center stage in neurotrauma and
      neurological diseases as they appear to play a dominant role in the inflammatory
      processes associated with these conditions. Previously, we reported that
      inhibiting NF-kappaB activation in astrocytes, using a transgenic mouse model
      (GFAP-IkappaBalpha-dn mice), results in improved functional recovery, increased
      white matter preservation and axonal sparing following spinal cord injury (SCI).
      In the present study, we sought to determine whether this improvement, due to
      inhibiting NF-kappaB activation in astrocytes, could be the result of enhanced
      oligodendrogenesis in our transgenic mice. METHODS: To assess oligodendrogenesis
      in GFAP-IkappaBalpha-dn compared to wild-type (WT) littermate mice following SCI,
      we used bromodeoxyuridine labeling along with cell-specific immuno
      histochemistry, confocal microscopy and quantitative cell counts. To further gain
      insight into the underlying molecular mechanisms leading to increased white
      matter, we performed a microarray analysis in naive and 3 days, 3 and 6 weeks
      following SCI in GFAP-IkappaBalpha-dn and WT littermate mice. RESULTS: Inhibition
      of astroglial NF-kappaB in GFAP-IkappaBalpha-dn mice resulted in enhanced
      oligodendrogenesis 6 weeks following SCI and was associated with increased levels
      of myelin proteolipid protein compared to spinal cord injured WT mice. The
      microarray data showed a large number of differentially expressed genes involved
      in inflammatory and immune response between WT and transgenic mice. We did not
      find any difference in the number of microglia/leukocytes infiltrating the spinal
      cord but did find differences in their level of expression of toll-like receptor
      4. We also found increased expression of the chemokine receptor CXCR4 on
      oligodendrocyte progenitor cells and mature oligodendrocytes in the transgenic
      mice. Finally TNF receptor 2 levels were significantly higher in the transgenic
      mice compared to WT following injury. CONCLUSIONS: These studies suggest that one
      of the beneficial roles of blocking NF-kappaB in astrocytes is to promote
      oligodendrogenesis through alteration of the inflammatory environment.

PMID- 23880093
TI  - Lipid metabolism is differentially modulated by salicylic acid and heptanoyl
      salicylic acid during the induction of resistance in wheat against powdery
      mildew.
AB  - Heptanoyl salicylic acid (HSA) is a salicylic acid (SA) derivative obtained by
      esterification of 2-OH benzoic acid with heptanoic acid. In wheat, the protection
      levels obtained against Blumeria graminis f. sp. tritici (Bgt) increased from 50%
      with SA to 95% with HSA. Using molecular, biochemical and cytological approaches,
      we investigated here how wheat lipid metabolism is differentially activated by SA
      and HSA in both infectious and non-infectious conditions, and how Bgt infectious
      process is altered by both inducers. First, in the absence of Bgt, continuous
      lipoxygenase (LOX)-encoding gene expression and corresponding activity were
      specifically induced by HSA. Moreover, compared to SA, HSA treatment resulted in
      earlier up-regulations of the phospholipase C2-encoding gene expression and it
      specifically affected the expression of a lipid transfer protein-encoding gene.
      In infectious context, both HSA and SA sprayings impaired penetration events and
      therefore haustorium formation, leading to less frequent fungal colonies. While
      this alteration only slowed down the evolution of Bgt infectious process in SA
      sprayed leaves, it completely impaired the establishment of successful infectious
      events in HSA-sprayed leaves. In addition, HSA induced continuous increases of a
      LOX-encoding gene expression and of the corresponding LOX activity when compared
      to SA-sprayed leaves. Lipid metabolism is therefore overall highly responsive to
      HSA spraying and could represent effective defence mechanism triggered during the
      induction of resistance in wheat toward Bgt. The concepts of priming and energy
      costs of the defences induced by SA and HSA are also discussed. 

PMID- 23880094
TI  - Low plasma levels of cholecalciferol and 13-cis-retinoic acid in tuberculosis:
      implications in host-based chemotherapy.
AB  - OBJECTIVE: The aim of this study was to estimate the concentration of
      cholecalciferol and 13-cis-retinoic acid (RA) in the plasma and pleural fluid of
      patients with tuberculosis (TB) against controls. METHODS: Plasma levels of
      cholecalciferol and 13-cis-RA were measured in 22 patients with TB and healthy
      controls and their pleural fluids levels were measured in 6 TB patients and
      diseased controls by established high-performance liquid chromatography-based
      procedure. RESULTS: Cholecalciferol levels in plasma and pleural fluid of
      patients with TB and healthy controls were 67.45 (10.71) nmol/L and 21.40 (8.58)
      nmol/L compared with 117.43 (18.40) nmol/L (P < 0.001) and 94.73 (33.34) nmol/L
      (P = 0.0049), respectively. 13-cis-RA level in the plasma of patients with TB and
      healthy controls were 1.51 (0.72) nmol/L and 6.67 (0.81) nmol/L (P < 0.001),
      respectively. 13-cis-RA was not detectable in pleural fluid. The levels of both
      the agents were lower in patients with TB than in controls. CONCLUSION: It was
      observed that in patients with TB there is a combined deficiency of
      cholecalciferol and 13-cis-RA compared with healthy volunteers. Because
      cholecalciferol and 13-cis-RA are in equilibrium with active ingredients of
      vitamins A and D, we feel that there is a combined deficiency of these vitamins
      in patients with TB. There is an evidence that concomitant vitamin A and D
      supplementation can kill intracellular Mycobacterium tuberculosis in vitro.
      Therefore, the observations made in this study can pave the path for a trial of
      combined supplementation of available formulations of vitamin A and D
      (cholecalciferol and 13-cis-RA) for novel anti-tubercular drug therapy. Because
      such an approach is host-based it has potential to treat even multidrug-resistant
      and extensively drug-resistant forms of TB.

PMID- 23880095
TI  - Effect of culture media and nutrients on biofilm growth kinetics of laboratory
      and clinical strains of Enterococcus faecalis.
AB  - OBJECTIVE: Enterococcus faecalis is a bacterial pathogen that is often associated
      with endodontic infections. Biofilm formation is a key virulence attribute in the
      pathogenicity of E. faecalis. In the present study, we comprehensively examined
      the effect of various culture media and nutrients on the development of E.
      faecalis biofilms. DESIGN: A reference strain and a clinical isolate of E.
      faecalis were used in all experiments for comparison. Commonly used liquid
      culture media with different nutrient compositions were used to support the
      development of E. faecalis biofilms in a time-dependent assay. E. faecalis
      biofilms were quantified by colony forming unit (CFU) and crystal violet (CV)
      assays. Biofilm architecture and cellular viability were evaluated by scanning
      electron microscopy and confocal laser scanning microscopy. RESULTS: Growth
      kinetics evaluated by CFU and CV assays and by microscopy showed that E. faecalis
      biofilms reached maturity at 72h. "Pg broth" (Tryptic Soy Broth with yeast
      extract, hemen and vitamin K) promoted E. faecalis biofilm formation more than
      Brain Heart Infusion broth or Tryptic Soy Broth. Addition of 2% glucose enhanced
      biofilm formation. Thus, it seems that nutrients such as hemen, vitamin K and
      glucose are important for E. faecalis for the formation of biofilms. CONCLUSION:
      The present study demonstrated that nutrient-rich media containing glucose
      enhances the formation of E. faecalis biofilms, which exhibit maturation at 72h.

PMID- 23880096
TI  - Evaluation of conformation against traits associated with dressage ability in
      unridden Iberian horses at the trot.
AB  - The work describes and compares the conformation traits and gait characteristics
      in the main native Iberian dressage Purebreds (Lusitano, Spanish and Menorca
      horses). In total, 4 strides belonging to each of 66 males (4-14 years old) were
      recorded at handled trot, using a 3D semi-automatic movement analysis system.
      Principal component analysis (PCA) and intraclass Correlations (iC) were
      computed. The Menorca Purebred showed proportionally higher limbs (23.8 and
      15.1cm for the forelimb cannon and pastern lengths), the Lusitano Purebred had
      larger inclinations (66.1 degrees , 37.7 degrees  and 47.9 degrees  for the
      scapula and pastern angles), and the Spanish Purebred presented a longer scapula
      (41.5 cm) and a larger hip angle (132.1 degrees ), apparently showing a better
      conformation for dressage gaits. However, the three breeds presented undesirable
      tarsus joint conformation (<155.5 degrees ) for dressage performance. In general,
      all of them showed good features in the kinematics of the forelimbs.
      Nevertheless, the functional capacity of their hindlimbs and linear parameters
      probably need to be improved for their competitiveness.

PMID- 23880097
TI  - Recognition advantage of happy faces: tracing the neurocognitive processes.
AB  - The present study aimed to identify the brain processes-and their time course
      underlying the typical behavioral recognition advantage of happy facial
      expressions. To this end, we recorded EEG activity during an expression
      categorization task for happy, angry, fearful, sad, and neutral faces, and the
      correlation between event-related-potential (ERP) patterns and recognition
      performance was assessed. N170 (150-180 ms) was enhanced for angry, fearful and
      sad faces; N2 was reduced and early posterior negativity (EPN; both, 200-320 ms)
      was enhanced for happy and angry faces; P3b (350-450 ms) was reduced for happy
      and neutral faces; and slow positive wave (SPW; 700-800 ms) was reduced for happy
      faces. This reveals (a) an early processing (N170) of negative affective valence
      (i.e., angry, fearful, and sad), (b) discrimination (N2 and EPN) of affective
      intensity or arousal (i.e., angry and happy), and (c) facilitated categorization
      (P3b) and decision (SPW) due to expressive distinctiveness (i.e., happy). In
      addition, N2, EPN, P3b, and SPW were related to categorization accuracy and
      speed. This suggests that conscious expression recognition and the typical happy
      face advantage depend on encoding of expressive intensity and, especially, on
      later response selection, rather than on the early processing of affective
      valence.

PMID- 23880098
TI  - Graduate admissions in clinical neuropsychology: the importance of undergraduate
      training.
AB  - Discussions of and recommendations for the training of clinical
      neuropsychologists exist at the doctoral, internship, and post-doctoral level.
      With few exceptions, the literature on undergraduate preparations in clinical
      neuropsychology is sparse and lacks empirical evidence. In the present study,
      graduate-level faculty and current trainees completed surveys about graduate
      school preparations. Faculty expectations of minimum and ideal undergraduate
      training were highest for research methods, statistics, and assessment.
      Preferences for "goodness of fit" also emerged as important admissions factors.
      These results offer evidence for desirable undergraduate preparations for
      advanced study in clinical neuropsychology. Although undergraduate training in
      psychology is intentionally broad, results from this study suggest that students
      who desire advanced study in clinical neuropsychology need to tailor their
      experiences to be competitive in the application process. The findings have
      implications for prospective graduate students, faculty who train and mentor
      undergraduates, and faculty who serve on admissions committees. 

PMID- 23880099
TI  - Population pharmacokinetics of tranexamic acid in adults undergoing cardiac
      surgery with cardiopulmonary bypass.
AB  - BACKGROUND: Interest in antifibrinolytic tranexamic acid (TA) has grown since the
      widespread removal of aprotinin, but its dosing during cardiac surgery is still
      debated. The objectives of this study were to investigate the population
      pharmacokinetics (PK) of TA given with either low- or high-dose continuous
      infusion schemes in adult cardiac surgery patients during cardiopulmonary bypass
      (CPB). METHODS: Patients were randomized to receive either low-dose (10 mg kg(-1)
      followed by an infusion of 1 mg kg(-1) h(-1) throughout the operation, and 1 mg
      kg(-1) into the CPB) or high-dose (30 mg kg(-1), then 16 mg kg(-1) h(-1), and 2
      mg kg(-1) into the CPB) TA. Serum TA concentrations were measured in 61 patients
      and the data were modelled using Monolix. RESULTS: TA concentrations were 28-55
      ug ml(-1) in the low-dose group and 114-209 ug ml(-1) in the high-dose group
      throughout surgery. TA PK was best described by a two-compartment open model. The
      main covariate effect was bodyweight, whereas the CPB did not influence the PK.
      Assuming a bodyweight of 70 kg, the population estimates were 4.8 litre h(-1) for
      clearance, 6.6 litre for the volume of the central compartment, 32.2 litre h(-1)
      for the diffusional clearance, and the peripheral volume of distribution was 10.8
      litre. CONCLUSIONS: The PK of TA was satisfactorily described by an open two
      compartmental model, which was used to propose a dosing scheme suitable for
      obtaining and maintaining the desired plasma concentration in a stable and narrow
      range in cardiac surgery patients.

PMID- 23880100
TI  - Study to determine the repeatability of supra-sternal Doppler (ultrasound cardiac
      output monitor) during general anaesthesia: effects of scan quality, flow volume,
      and increasing age.
AB  - BACKGROUND: The ultrasound cardiac output monitor (USCOM) is a continuous wave
      Doppler system designed to measure cardiac output (CO) non-invasively and
      intermittently either from the pulmonary or from the aortic valve. USCOM scan
      quality is critical to obtaining reliable data and during anaesthesia it is said
      to deteriorate with increasing age. The aim of this study was to investigate the
      effect of age on supra-sternal USCOM scan repeatability during anaesthesia.
      METHODS: We performed a series of 6 USCOM scans in 180 patients of all ages after
      induction for routine surgery. A 12-point Cattermole (CS) score and 10-point
      insonation (IS) score were used to evaluate scan quality and ease of insonation.
      The coefficients of variation (CVs) of USCOM variables [CO, peak velocity, stroke
      volume index (SVI) and the corrected flow time] were derived from the series of
      six readings. RESULTS: In >95% of young patients (age <50 yr), it was easy to
      obtain a good-quality USCOM scan (CS>8). In these patients, repeatability of
      serial readings was good with CVs<5% and precision of less than +/-10%. In older
      patients (>50 yr), scan quality and ease of insonation declined, with >25% of
      patients >60 yr having unreliable USCOM scans (CS<5). In these patients, the CV
      was >5-10%. In several elderly patients (>65 yr), we failed to locate the USCOM
      signal. Average scan time increased with age (30 to >60 s). SVI was also strongly
      correlated with scan quality (R(2)=0.77). CONCLUSIONS: Increasing age has a
      significant effect on USCOM scan quality and data reliability.

PMID- 23880101
TI  - Phospho-GSK-3beta is involved in the high-glucose-mediated lipid deposition in
      renal tubular cells in diabetes.
AB  - The phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) pathway mediates
      the high-glucose-induced lipid accumulation in the renal tubular cells in
      diabetes. Studies have revealed that the downstream target genes of phospho-Akt,
      BCL2-associated death promoter (Bad) and glycogen synthase kinase-3beta (GSK
      3beta) are associated with lipid accumulation in hepatic cells and preadipocytes.
      In the present study, it was revealed that the phospho-Akt, phospho-Bad, phosphor
      GSK-3beta contents and lipogenesis were increased in the renal tubular cells of
      diabetic rats. However, in high-glucose-treated human renal tubular cells, only
      the phospho-GSK-3beta content increased without an alteration in the phospho-Bad
      content, which could be reversed by treatment with a short hairpin RNA vector
      aimed at Akt. Inhibiting GSK-3beta activity using TWS119 increased the sterol
      regulatory element binding protein-1 (SREBP-1) content and lipogenesis in renal
      tubular cells. Furthermore, the exogenous expression of wild-type GSK-3beta
      enhanced the level of phospho-GSK-3beta in high-glucose-stimulated renal tubular
      cells, followed by increased SREBP-1 expression and lipogenesis. Moreover,
      exogenous expression of mutant GSK-3beta (via vector S9A) prevented the increase
      in SREBP-1 expression and cellular lipogenesis by decreasing the phospho-GSK
      3beta content and increasing the GSK-3beta activity in high-glucose-treated
      cells. These data suggested that phospho-GSK-3beta is involved in the high
      glucose-mediated increase of SREBP-1 expression and triglyceride content in renal
      tubular cells in diabetes. 

PMID- 23880102
TI  - High HIV-1 prevalence, risk behaviours, and willingness to participate in HIV
      vaccine trials in fishing communities on Lake Victoria, Uganda.
AB  - INTRODUCTION: HIV epidemics in sub-Saharan Africa are generalized, but high-risk
      subgroups exist within these epidemics. A recent study among fisher-folk
      communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence
      (4.9/100 person-years). However, those findings may not reflect population-wide
      HIV rates in FFC since the study population was selected for high-risk behaviour.
      METHODS: Between September 2011 and March 2013, we conducted a community-based
      cohort study to determine the population representative HIV rates and willingness
      to participate (WTP) in hypothetical vaccine trials among FFC, Uganda. At
      baseline (September 2011-January 2012), a household enumeration census was done
      in eight fishing communities (one lakeshore and seven islands), after which a
      random sample of 2200 participants aged 18-49 years was selected from 5360
      individuals. Interviewer-administered questionnaire data were collected on HIV
      risk behaviours and WTP, and venous blood was collected for HIV testing using
      rapid HIV tests with enzyme-linked immunosorbent assay (EIA) confirmation.
      Adjusted prevalence proportion ratios (adj.PPRs) of HIV prevalence were
      determined using log-binomial regression models. RESULTS: Overall baseline HIV
      prevalence was 26.7% and was higher in women than men (32.6% vs. 20.8%,
      p<0.0001). Prevalence was lower among fishermen (22.4%) than housewives (32.1%),
      farmers (33.1%) and bar/lodge/restaurant workers (37%). The adj.PPR of HIV was
      higher among women than men (adj.PPR =1.50, 95%; 1.20, 1.87) and participants
      aged 30-39 years (adj.PPR=1.40, 95%; 1.10, 1.79) and 40-49 years (adj.PPR=1.41,
      95%; 1.04, 1.92) compared to those aged 18-24 years. Other factors associated
      with HIV prevalence included low education, previous marriage, polygamous
      marriage, alcohol and marijuana use before sex. WTP in hypothetical vaccine
      trials was 89.3% and was higher in men than women (91.2% vs. 87.3%, p=0.004) and
      among island communities compared to lakeshore ones (90.4% vs. 85.8%, p=0.004).
      CONCLUSIONS: The HIV prevalence in the general fisher-folk population in Uganda
      is similar to that observed in the "high-risk" fisher folk. FFC have very high
      levels of willingness to participate in future HIV vaccine trials.

PMID- 23880103
TI  - Cardiomyopathy in young adults with classic mitral valve prolapse.
AB  - BACKGROUND: In some inherited connective tissue diseases with involvement of the
      cardiovascular system, for example, Marfan syndrome, early impairment of left
      ventricular function, which have been described as Marfan-related cardiomyopathy
      has been reported. Our aim was to evaluate the left ventricular function in young
      adults with mitral valve prolapse without significant mitral regurgitation using
      two-dimensional strain imaging and to determine the possible role of the
      transforming growth factor-beta pathway in its deterioration. METHODS: We studied
      78 young adults with mitral valve prolapse without mitral regurgitation in
      comparison with 80 sex-matched and age-matched healthy individuals. Longitudinal
      strain and strain rates were defined using spackle tracking. Concentrations of
      transforming growth factor-beta1 and beta2 in serum were determined by enzyme
      linked immunosorbent assays. RESULTS: In 29 patients, classic relapse was
      identified with a leaflet thickness of >= 5 mm; 49 patients had a non-classic
      mitral valve prolapse. Despite the similar global systolic function, a
      significant reduction in global strain was found in the classic group (-15.5 +/-
      2.9%) compared with the non-classic group (-18.7 +/- 3.8; p = 0.0002) and the
      control group (-19.6 +/- 3.4%; p < 0.0001). In young adults with non-classic
      prolapse, a reduction in longitudinal deformation was detected only in septal
      segments. Transforming growth factor-beta1 and beta2 serum levels were elevated
      in patients with classic prolapse as compared with the control group and the non
      classic mitral valve prolapse group. CONCLUSIONS: These changes in the
      deformations may be the first signs of deterioration of the left ventricular
      function and the existence of primary cardiomyopathy in young adults with mitral
      valve prolapse, which may be caused by increased transforming growth factor-beta
      signalling.

PMID- 23880104
TI  - The disconnect between classical biostatistics and the biological data mining
      community.

PMID- 23880106
TI  - Comparative antioxidant status in freshwater fish Carassius auratus exposed to
      six current-use brominated flame retardants: a combined experimental and
      theoretical study.
AB  - Decabromodiphenyl ether (BDE-209) and several non-polybrominated diphenyl ether
      (PBDE) brominated flame retardants (BFRs), such as tetrabromobisphenol A (TBBPA),
      hexabromocyclododecane (HBCD), decabromodiphenyl ethane (DBDPE), hexabromobenzene
      (HBB) and pentabromotoluene (PBT), are persistent halogenated contaminants
      ubiquitously detected in aquatic systems. However, data on comparative
      toxicological effects of these BFRs are lacking for fish. In this study, a
      combined experimental and theoretical approach was used to compare and analyze
      the effects of these BFRs on biochemical biomarkers in liver of Carassius auratus
      injected intraperitoneally with different doses (10 and 100mg/kg) for 7, 14 and
      30 days. Oxidative stress was evoked evidently for the prolonged exposure,
      represented by the significantly altered indices (superoxide dismutase, catalase,
      glutathione peroxidase, reduced glutathione, and malondialdehyde). The integrated
      biomarker response (IBR) index ranked biotoxicity as: PBT>HBB>HBCD>TBBPA>BDE
      209>DBDPE. Quantum chemical calculations (electronic parameters, frontier
      molecular orbitals, and Wiberg bond order) were performed for theoretical
      analysis. Notably, some descriptors were correlated with the toxicity order,
      probably implying the existence of a potential structure-activity relationship
      when more BFRs were included. Besides, theoretical calculations also provided
      some valuable information regarding the molecular characteristics and metabolic
      pathways of these current-use BFRs, which may facilitate the understanding on
      their environmental behavior and fate. Overall, this study adopted a combined
      experimental and theoretical method for the toxicological determination and
      analysis of the BFRs, which may also be considered in future ecotoxicological
      studies. 

PMID- 23880105
TI  - Factors predicting the use of therapeutic hypothermia and survival in unconscious
      out-of-hospital cardiac arrest patients admitted to the ICU.
AB  - INTRODUCTION: Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest
      (OHCA) was adopted early in Norway. Since 2004 the general recommendation has
      been to cool all unconscious OHCA patients treated in the intensive care unit
      (ICU), but the decision to cool individual patients was left to the responsible
      physician. We assessed factors that were associated with use of TH and predicted
      survival. METHOD: We conducted a retrospective observational study of
      prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at
      three university hospitals. RESULTS: A total of 715 unconscious patients older
      than 18 years of age, who suffered OHCA of both cardiac and non-cardiac causes,
      were included. With an overall TH use of 70%, the survival to discharge was 42%,
      with 90% of the survivors having a favourable cerebral outcome. Known positive
      prognostic factors such as witnessed arrest, bystander cardio pulmonary
      resuscitation (CPR), shockable rhythm and cardiac origin were all positive
      predictors of TH use and survival. On the other side, increasing age predicted a
      lower utilisation of TH: Odds Ratio (OR), 0.96 (95% CI, 0.94 to 0.97); as well as
      a lower survival: OR 0.96 (95% CI, 0.94 to 0.97). Female gender was also
      associated with a lower use of TH: OR 0.65 (95% CI, 0.43 to 0.97); and a poorer
      survival: OR 0.57 (95% CI, 0.36 to 0.92). After correcting for other prognostic
      factors, use of TH remained an independent predictor of improved survival with OR
      1.91 (95% CI 1.18-3.06; P <0.001). Analysing subgroups divided after initial
      rhythm, these effects remained unchanged for patients with shockable rhythm, but
      not for patients with non-shockable rhythm where use of TH and female gender lost
      their predictive value. CONCLUSIONS: Although TH was used in the majority of
      unconscious OHCA patients admitted to the ICU, actual use varied significantly
      between subgroups. Increasing age predicted both a decreased utilisation of TH as
      well as lower survival. Further, in patients with a shockable rhythm female
      gender predicted both a lower use of TH and poorer survival. Our results indicate
      an underutilisation of TH in some subgroups. Hence, more research on factors
      affecting TH use and the associated outcomes in subgroups of post-resuscitation
      patients is needed.

PMID- 23880107
TI  - Amperometric aptasensor for thrombin detection using enzyme-mediated direct
      electrochemistry and DNA-based signal amplification strategy.
AB  - In this work, a new electrochemical aptasensor based on direct electron transfer
      and electrocatalysis of horseradish peroxidase (HRP) using exonuclease-catalyzed
      target recycling and hybridization chain reaction (HCR) for signal amplification
      was developed for highly sensitive detection of thrombin. The electrochemical
      signal was originated from HRP without the addition or labeling of redox probes.
      To construct the aptasensor, the capture probe was immobilized on gold
      nanoparticles (AuNPs) modified electrode for the following hybridization with the
      complementary thrombin binding aptamer. In the presence of thrombin, the
      formation of aptamer-thrombin complex would result in the dissociation of aptamer
      from the double-strand DNA (dsDNA). Subsequently, with the employment of
      exonuclease, aptamer was selectively digested and thrombin could be released for
      analyte recycling. The capture probe and two hairpin helper DNAs lead to the
      formation of extended dsDNA polymers through HCR on the electrode surface. Then
      the biotin-labeled dsDNA polymers could introduce numerous avidin-labeled HRP,
      resulting in significantly amplified electrochemical signal through the direct
      electrochemistry and electrocatalysis of HRP. The proposed strategy combined the
      amplification of analyte recycling and HCR, as well as the inherent
      electroactivity and catalytic activity of HRP, which exhibited high sensitivity
      for thrombin determination with an ultra-low detection limit of 1.2*10(-13) M.
      Moreover, the detection scheme could be easily extended to the detection of other
      biomolecules. 

PMID- 23880108
TI  - Sensitive sugar detection using 4-aminophenylboronic acid modified graphene.
AB  - A sensitive electrochemical active interface for sugar sensing based on the
      specific boronic acid-diol binding was established. The sensing matrix was formed
      by stirring a suspension of graphene oxide (GO) with 4-aminophenylboronic acid
      (APBA). The resulting composite consists of a water insoluble precipitate of
      reduced graphene oxide (rGO) with APBA incorporated into the rGO matrix.
      Differential pulse voltammetry (DPV) on glassy carbon electrodes modified with
      rGO/APBA was used for the detection of fructose, mannose and glucose. The
      fabricated sensor exhibited a wide linear range with detection limits of 100 nM
      for fructose, and around 800 nM for mannose and glucose.

PMID- 23880109
TI  - Sensitive competitive immunoassay of multiple mycotoxins with non-fouling antigen
      microarray.
AB  - Various mycotoxins with strong carcinogenesis and toxicity are fatal threats in
      food safety, and require highly sensitive and high-throughput detections greatly.
      Herein a fluorescent competitive immunoassay microarray based on a non-fouling
      polymer brush, poly[(ethylene glycol) methacrylate-co-glycidyl methacrylate]
      (POEGMA-co-GMA) is explored to sensitively detect multiple mycotoxins with
      aflatoxin B1 (AFB1), ochratoxin A (OTA) and zearalenone (ZEN) as template
      targets. Due to uniformly large protein loading and high resistance to
      nonspecific protein absorption of the POEGMA-co-GMA brush, the optimal microarray
      exhibits wide dynamic ranges of three orders of magnitudes and low detection
      limits of 4, 4 and 3 pg mL(-1), respectively, which is much better than that
      obtained with an epoxy-functionalized antigen microarray, and is comparable or
      even better than the conventional ELISA method. This work offers a powerful high
      throughput tool to fast screening of toxins in food quality and environmental
      monitoring.

PMID- 23880110
TI  - Some characteristics of amplified music through hearing aids.
AB  - Hearing aids are a relatively non-invasive means of reducing the negative effects
      of hearing loss on an individual who does not require a cochlear implant. Music
      amplified through hearing aids has some interesting characteristics but high
      fidelity is not typically one of them. This poses a serious problem for the
      investigator who wants to perform research on music with hearing impaired
      individuals who wear hearing aids. If the signal at the tympanic membrane is
      somewhat distorted then this has consequences for the assessment of music
      processing when examining both the peripheral and the central auditory system. In
      this review article on the subject of hearing aids and music, some of the
      acoustical differences between speech and music will be described. Following
      this, a discussion about what hearing aids do well and also less well for music
      as an input will be presented. Finally, some recommendations are made about what
      can be done for hearing-impaired individuals who wear hearing aids to listen to
      music.

PMID- 23880111
TI  - Nitric oxide and reactive oxygen species in plant biotic interactions.
AB  - Nitric oxide (NO) and reactive oxygen species (ROS) are important signaling
      molecules in plants. Recent progress has been made in defining their role during
      plant biotic interactions. Over the last decade, their function in disease
      resistance has been highlighted and focused a lot of investigations. Moreover, NO
      and ROS have recently emerged as important players of defense responses after
      herbivore attacks. Besides their role in plant adaptive response development, NO
      and ROS have been demonstrated to be involved in symbiotic interactions between
      plants and microorganisms. Here we review recent data concerning these three
      sides of NO and ROS functions in plant biotic interactions. 

PMID- 23880113
TI  - Prognostic factors for medically intractable epilepsy: a systematic review.
AB  - OBJECTIVE: One third of all epilepsy patients have medically intractable
      epilepsy. Knowledge of prognostic factors that, in an early therapeutic stage of
      epilepsy, herald intractability could facilitate patient management. In this
      systematic review, we examined the evidence for independent prognostic factors of
      intractability in patients with epilepsy. METHODS: MEDLINE and EMBASE were
      searched for cohort studies reporting on prognostic factors for medically
      intractable epilepsy. After selection of abstracts, full-text articles were
      obtained and their quality was assessed by two reviewers, using the QUIPS
      checklist. All independent prognostic factors in the individual studies were
      summarized. RESULTS: Eleven cohort studies were included, of which ten hospital
      based. Younger age at seizure onset, symptomatic etiology, high initial seizure
      frequency, medical history, epileptic EEG abnormalities, and failure of previous
      antiepileptic-drugs (AEDs) were documented as independent prognostic factors of
      intractability in at least 2 of the 11 studies; none of these factors was
      reported in all 11 studies. None of the studies considered genetic,
      neurobiological, or immunological factors. The studies were of moderate quality,
      mostly because they did not provide a conceptual model for the choice of
      predictors. Heterogeneity in study design, population, candidate prognostic
      factors, and outcome definitions precluded statistical pooling. CONCLUSIONS:
      While potentially relevant prognosticators of medically intractable epilepsy have
      been identified, the evidence for these factors is not consistent. There is a
      need for well-designed prognostic population-based cohort studies that also
      include pharmacological, genetic, neurobiological, and immunological factors. A
      valid model for the early prediction of medically intractable epilepsy could
      improve patient management.

PMID- 23880112
TI  - Sunitinib enhances neuronal survival in vitro via NF-kappaB-mediated signaling
      and expression of cyclooxygenase-2 and inducible nitric oxide synthase.
AB  - BACKGROUND: Angiogenesis is tightly linked to inflammation and cancer. Regulation
      of angiogenesis is mediated primarily through activation of receptor tyrosine
      kinases, thus kinase inhibitors represent a new paradigm in anti-cancer therapy.
      However, these inhibitors have broad effects on inflammatory processes and
      multiple cell types. Sunitinib is a multitarget receptor tyrosine kinase
      inhibitor, which has shown promise for the treatment of glioblastoma, a highly
      vascularized tumor. However, there is little information as to the direct effects
      of sunitinib on brain-derived neurons. The objective of this study is to explore
      the effects of sunitinib on neuronal survival as well as on the expression of
      inflammatory protein mediators in primary cerebral neuronal cultures. METHODS:
      Primary cortical neurons were exposed to various doses of sunitinib. The drug
      treated cultures were assessed for survival by MTT assay and cell death by
      lactate dehydrogenase release. The ability of sunitinib to affect NF-kappaB, COX2
      and NOS2 expression was determined by western blot. The NF-kappaB inhibitors
      dicoumarol, SN50 and BAY11-7085 were employed to assess the role of NF-kappaB in
      sunitinib-mediated effects on neuronal survival as well as COX2 and NOS2
      expression. RESULTS: Treatment of neuronal cultures with sunitinib caused a dose
      dependent increase in cell survival and decrease in neuronal cell death. Exposure
      of neurons to sunitinib also induced an increase in the expression of NF-kappaB,
      COX2 and NOS2. Inhibiting NF-kappaB blunted the increase in cell survival and
      decrease in cell death evoked by sunitinib. Treatment of cell cultures with both
      sunitinib and NF-kappaB inhibitors mitigated the increase in COX2 and NOS2 caused
      by sunitinib. CONCLUSIONS: Sunitinib increases neuronal survival and this
      neurotrophic effect is mediated by NF-kappaB. Also, the inflammatory proteins
      COX2 and NOS2 are upregulated by sunitinib in an NF-kappaB-dependent manner.
      These data are in agreement with a growing literature suggesting beneficial
      effects for inflammatory mediators such as NF-kappaB, COX2 and NOS2 in neurons.
      Further work is needed to fully explore the effects of sunitinib in the brain and
      its possible use as a treatment for glioblastoma. Finally, sunitinib may be
      useful for the treatment of a range of central nervous system diseases where
      neuronal injury is prominent.

PMID- 23880114
TI  - Marital distress prospectively predicts poorer cellular immune function.
AB  - OBJECTIVE: Distressed marriages enhance risk for a variety of health problems.
      Immune dysregulation is one potential mechanism; cross-sectional studies have
      demonstrated that marital distress is linked to maladaptive immune alterations.
      The current study filled an important gap in the literature by examining the
      ability of marital distress to prospectively predict immune alterations over a
      two-year period. METHOD: Participants were 90 couples (N=180 individuals;
      Mage=25.67) married less than a year at the time of their first study visit. Both
      members of a couple completed a baseline assessment of marital quality and
      provided blood samples at baseline and two years later. 63 couples (N=123
      individuals) completed the follow-up assessment. RESULTS: Spouses in more
      distressed marriages had larger declines in cellular immune function over time
      than spouses in less distressed marriages. Furthermore, the results were highly
      consistent across two different indices, proliferative responses to two mitogens,
      concanavalin A (Con A) and phytohemagglutinin (PHA). CONCLUSIONS: Marital
      distress has a variety of negative health consequences. The current study
      provided important evidence that marital distress has longer-term immune
      consequences. Accordingly, the present results provide a glimpse into the
      pathways through which marital distress may impact health over time.

PMID- 23880115
TI  - Younger age at diagnosis is associated with panenteric, but not more aggressive,
      Crohn's disease.
AB  - BACKGROUND & AIMS: Crohn's disease (CD) diagnosed in pediatric patients has been
      reported to have a more aggressive phenotype and course, with a greater
      prevalence of upper gastrointestinal involvement, than in adults. However,
      studies have not accounted for differences in diagnostic tests. We aimed to
      discern whether, in fact, CD diagnosed in childhood has a different outcome than
      CD diagnosed in adults. METHODS: We performed comprehensive medical chart reviews
      of 571 patients with CD (451 with complete data) who were followed in a single
      referral inflammatory bowel disease clinic in Winnipeg, Canada, from 1993-2012.
      For specific time intervals, we determined types and numbers of imaging studies
      performed and parameters of disease phenotype, including age at diagnosis
      according to the Montreal classification (A1 diagnosed <17 years of age, A2
      diagnosed 17-40 years, and A3 diagnosed >40 years). RESULTS: Within 1 year of
      diagnosis, a higher proportion of A1 patients had upper gastrointestinal
      involvement and ileocolonic (L3) disease than A2 or A3 patients. These
      differences could be partly accounted for by the diagnostic tests performed
      during this time period. Although A1 patients underwent more extensive imaging
      studies, they had a lower prevalence of complicated disease, particularly
      compared with A3 patients. After a median follow-up period of 11.1 years,
      complicated disease behavior (B2 [structuring] or B3 [penetrating]) was similar
      among the 3 groups. Nonetheless, at the end of the study period, rates of
      inflammatory bowel disease-related abdominal surgery were significantly lower for
      A1 than A2 patients (odds ratio, 0.63; 95% confidence interval, 0.41-0.98) but
      not for A3 patients (odds ratio, 0.71; 95% confidence interval, 0.40-1.27).
      CONCLUSIONS: On the basis of a database analysis of different age groups of
      patients with CD, studies of disease phenotypes among different cohorts should
      account for different patterns of diagnostic imaging evaluation. Our data show
      that although children are at increased risk of panenteric disease, they are not
      more likely to have more complicated disease or undergo surgery than adults.

PMID- 23880116
TI  - Tensions inherent in the evolving role of the infection preventionist.
AB  - BACKGROUND: The role of infection preventionists (IPs) is expanding in response
      to demands for quality and transparency in health care. Practice analyses and
      survey research have demonstrated that IPs spend a majority of their time on
      surveillance and are increasingly responsible for prevention activities and
      management; however, deeper qualitative aspects of the IP role have rarely been
      explored. METHODS: We conducted a qualitative content analysis of in-depth
      interviews with 19 IPs at hospitals throughout the United States to describe the
      current IP role, specifically the ways that IPs effect improvements and the
      facilitators and barriers they face. RESULTS: The narratives document that the IP
      role is evolving in response to recent changes in the health care landscape and
      reveal that this progression is associated with friction and uncertainty.
      Tensions inherent in the evolving role of the IP emerged from the interviews as 4
      broad themes: (1) expanding responsibilities outstrip resources, (2) shifting
      role boundaries create uncertainty, (3) evolving mechanisms of influence involve
      trade-offs, and (4) the stress of constant change is compounded by chronic
      recurring challenges. CONCLUSION: Advances in implementation science, data
      standardization, and training in leadership skills are needed to support IPs in
      their evolving role.

PMID- 23880117
TI  - Algorithm to reduce unnecessary isolation days in patients with a history of
      colonization by antimicrobial-resistant organisms.
AB  - To determine the need of isolation precautions upon admission, we created and
      tested an algorithm based on a total of 474 patients with a history of carriage
      of an antibiotic-resistant organism. Using the algorithm upon patient admission
      reduced unnecessary isolations by almost 60% while maintaining a high sensitivity
      to predict persisting antibiotic-resistant organism colonization. 

PMID- 23880118
TI  - Cheatham platinum stent implantation in children with coarctation of the aorta:
      single-centre short-term, intermediate-term, and long-term results from Turkey.
AB  - OBJECTIVES: Our aim was to evaluate patients who were treated by percutaneous
      stent implantation. METHODS: Patients with aortic coarctation (n = 35) who had
      been treated with 38 stents - 12 bare and 26 covered - were evaluated. The
      demographics and procedural and follow-up data were recorded from hospital
      registers and compared according to patient specifications, for example, weight
      and coarctation nature. RESULTS: The procedure was successful in all patients.
      There was a statistically significant difference between the patients with native
      coarctation (n = 17) and those with recurrent coarctation (n = 18) in terms of
      pre-procedural blood pressures, systolic gradients, coarctation diameters, and
      the ratio of the coarctation site diameter to the descending aorta diameter.
      Although all patients received antihypertensive drugs before the procedure, the
      drug was discontinued in 26 patients during follow-up (p < 0.001). Stent
      migration was observed in four patients with recurrent coarctation (11.4%), and
      peripheral arterial injury was seen in three patients (8.5%). The mean follow-up
      time was 34 +/- 16 months. On average, 21 (6-42) months after the procedure, six
      patients underwent cardiac catheterisation. At least 2 years after the procedure,
      tomography was performed in 20 patients (57.2%). Patients who were evaluated by
      multi-slice computerised tomography revealed no pathologies. There was no
      statistically significant difference between the five patients weighing less than
      20 kg and the other 30 patients in terms of demographic and procedural
      characteristics, procedure success and complication rates, and follow-up data.
      CONCLUSION: Stent implantation for aortic coarctation is a method yielding
      satisfactory results in reducing coarctation gradients, efficient enlargement of
      the lesion area, and resolution of hypertension for children, including those
      weighing less than 20 kg.

PMID- 23880119
TI  - Energy monitoring and analysis during deformation of bedded-sandstone: use of
      acoustic emission.
AB  - This paper investigates the mechanical behaviour and energy releasing
      characteristics of bedded-sandstone with bedding layers in different
      orientations, under uniaxial compression. Cylindrical sandstone specimens (54 mm
      diameter and 108 mm height) with bedding layers inclined at angles of 10 degrees
      , 20 degrees , 35 degrees , 55 degrees , and 83 degrees  to the minor principal
      stress direction, were produced to perform a series of Uniaxial Compressive
      Strength (UCS) tests. One of the two identical sample sets was fully-saturated
      with water before testing and the other set was tested under dry conditions. An
      acoustic emission system was employed in all the testing to monitor the acoustic
      energy release during the whole deformation process of specimens. From the test
      results, the critical joint orientation was observed as 55 degrees  for both dry
      and saturated samples and the peak-strength losses due to water were 15.56%,
      20.06%, 13.5%, 13.2%, and 13.52% for the bedding orientations 10 degrees , 20
      degrees , 35 degrees , 55 degrees , and 83 degrees , respectively. The failure
      mechanisms for the specimens with bedding layers in 10 degrees , 20 degrees 
      orientations showed splitting type failure, while the specimens with bedding
      layers in 55 degrees , 83 degrees  orientations were failed by sliding along a
      weaker bedding layer. The failure mechanism for the specimens with bedding layers
      in 35 degrees  orientation showed a mixed failure mode of both splitting and
      sliding types. Analysis of the acoustic energy, captured from the acoustic
      emission detection system, revealed that the acoustic energy release is
      considerably higher in dry specimens than that of the saturated specimens at any
      bedding orientation. In addition, higher energy release was observed for
      specimens with bedding layers oriented in shallow angles (which were undergoing
      splitting type failures), whereas specimens with steeply oriented bedding layers
      (which were undergoing sliding type failures) showed a comparatively less energy
      release under both dry and saturated conditions. Moreover, a considerable amount
      of energy dissipation before the ultimate failure was observed for specimens with
      bedding layers oriented in shallow angles under both dry and saturated
      conditions. These results confirm that when rock having bedding layers inclined
      in shallow angles the failures could be more violent and devastative than the
      failures of rock with steeply oriented bedding layers.

PMID- 23880120
TI  - Comparison between experimental and 2-D numerical studies of multiple scattering
      in Inconel600 by means of array probes.
AB  - Ultrasonic non-destructive testing of polycrystalline structures can be disturbed
      by scattering at grain boundaries. Understanding and modeling this so-called
      "structural noise" is crucial for characterization as well as detection purposes.
      Structural noise can be considered as a fingerprint of the material under
      investigation, since it contains information about its microstructure. The
      interpretation of experimental data necessitates an accurate comprehension of
      complex phenomena that occur in multiple scattering media and thus robust
      scattering models. In particular, numerical models can offer the opportunity to
      realize parametrical studies on controlled microstructures. However, the ability
      of the model to simulate wave propagation in complex media must be validated. In
      that perspective, the main objective of the present work is to evaluate the
      ability of the finite-element code ATHENA 2D to reproduce typical features of
      multiple wave scattering in the context of ultrasonic non-destructive evaluation,
      with an array of sources and receivers. Experiments were carried out with a 64
      element array, around 2 MHz. The sample was a mock-up of Inconel600 exhibiting a
      coarse grain structure with a known grain size distribution. The numerical model
      of this microstructure is based on Voronoi diagrams. Two physical parameters were
      used to compare numerical and experimental data: the coherent backscattering
      peak, and the singular value distribution of the array response matrix. Though
      the simulations are 2-D, a good agreement was found between simulated and
      experimental data.

PMID- 23880121
TI  - Maternal and child under-nutrition in rural and urban communities of Lagos state,
      Nigeria: the relationship and risk factors.
AB  - BACKGROUND: Poor nutritional status of mothers has a direct and indirect
      consequence on their own health and that of their children. The objective of this
      study was to determine the relationship between nutritional status of mothers and
      their children and the risk factors for under-nutrition among mothers and
      children in rural and urban communities of Lagos State, Nigeria. METHODS: This
      was a cross sectional survey conducted using the multistage random sampling
      technique. A total of 300 mother-child pairs were studied, consisting of 150 each
      from rural and urban communities. Under-nutrition in mothers and children was
      determined using standard criteria. RESULTS: The prevalence of under-nutrition
      among mothers was significantly higher in rural than urban communities (10.7% vs.
      2.7%, p = 0.014). The prevalences of underweight and stunted children were also
      significantly higher in rural than urban communities (19.4% vs. 9.3%, p < 0.001)
      and (43.3% vs. 12.6%, p < 0.001) respectively. In rural communities, the risk of
      stunted mothers having children with stunting was about 7 times higher than those
      who were not (OR 6.7, 95% CI = 1.4-32.0, p = 0.007). In urban communities,
      undernourished mothers have about 11 and 12 times risk of having children with
      underweight and wasting respectively (OR 11.2, 95% CI = 1.4-86.5, p = 0.005) and
      (OR 12.3, 95% CI = 1.6-95.7, p = 0.003) respectively. The identified risk factors
      for maternal and child under nutrition differs across rural and urban
      communities. CONCLUSIONS: The prevalence of maternal and child under-nutrition is
      high in both communities although higher in rural communities. Efforts at
      reducing the vicious cycle of under-nutrition among mothers and children should
      concentrate on addressing risk factors specific for each community.

PMID- 23880123
TI  - Testing vision: from laboratory psychophysical tests to clinical evaluation.

PMID- 23880122
TI  - Anemia is an independent prognostic factor in intracerebral hemorrhage: an
      observational cohort study.
AB  - INTRODUCTION: To date only two studies have evaluated anemia status in acute
      intracerebral hemorrhage (ICH) reporting that on admission anemia (OAA) was
      associated with larger hematoma volume, and lower hemoglobin levels during
      hospital stay, which related to poorer outcome. The question remains whether
      anemia influences outcome through related volume-effects or itself has an
      independent impact? METHODS: This single-center investigation included 435
      consecutive patients with spontaneous ICH admitted to the Department of Neurology
      over five years. Functional short- and long-term outcome (3 months and 1 year)
      were analyzed for anemia status. Multivariate logistic and graphical regression
      analyses were calculated for associations of anemia and to determine independent
      effects on functional outcome. It was decided to perform a separate analysis for
      patients with ICH-volume <30 cm3 (minor-volume-ICH). RESULTS: Overall short-term
      outcome was worse in anemic patients (mRS[4-6] OAA = 93.3% vs. non-OAA = 61.2%, P
      < 0.01), and there was a further shift towards an increased long-term mortality
      (P = 0.02). The probability of unfavorable long-term-outcome (mRS[4-6]) in OAA
      was elevated 7-fold (OR:7.5; P < 0.01). Receiver operating characteristics curve
      (ROC) analysis revealed a positive but poor association of ICH-volume and anemia
      (AUC = 0.67) suggesting volume-undriven outcome-effects of anemia (AUC = 0.75).
      Multivariate regression analyses revealed that anemia, besides established
      parameters, has the strongest relation to unfavorable outcome (OR:3.0; P < 0.01).
      This is even more pronounced in minor-volume-ICH (OR:5.6; P < 0.01). CONCLUSIONS:
      Anemia seems to be a previously unrecognized significant predictor of unfavorable
      functional outcome with independent effects beyond its association with larger
      hemorrhage volumes. The recognition of anemia and its treatment may possibly
      influence outcome after ICH and as such prospective interventional studies are
      warranted.

PMID- 23880124
TI  - Spatial frequency selectivity of visual suppression during convergence eye
      movements.
AB  - Visual suppression of low-spatial frequency information during eye movements is
      believed to contribute to a stable perception of our visual environment. While
      visual perception has been studied extensively during saccades, vergence has been
      somewhat neglected. Here, we show that convergence eye movements reduce contrast
      sensitivity to low spatial frequency information around the onset of the eye
      movements, but do not affect sensitivity to higher spatial frequencies. This
      suggests that visual suppression elicited by convergence eye movements may have
      the same temporal and spatial characteristics as saccadic suppression. 

PMID- 23880125
TI  - Contour interaction for foveal acuity targets at different luminances.
AB  - Single-letter visual acuity is impaired by nearby flanking stimuli, a phenomenon
      known as contour interaction. We showed previously that when foveal acuity is
      degraded by a reduction of letter contrast, both the magnitude and angular
      spatial extent of foveal contour interaction remain unchanged. In this study, we
      asked whether contour interaction also remains unchanged when foveal visual
      acuity is degraded by a reduction of the target's background luminance. Percent
      correct letter identification was measured for isolated, near-threshold black
      Sloan letters and for letters surrounded by 4 flanking bars in 10 normal
      observers, 5 at Anglia Ruskin University, UK (ARU) and 5 at Palacky University,
      Czech Republic (PU). A stepwise reduction in the background luminance over 3 log
      units resulted in an approximately threefold increase in the near-threshold
      letter size. At each background luminance, black flanking bars with a width equal
      to 1 letter stroke were presented at separations between approximately 0.45 and
      4.5 min arc (ARU) or 0.32 and 3.2 min arc (PU). The results indicate that the
      angular extent of contour interaction remains unchanged at approximately 4 min
      arc at all background luminances. On the other hand, the magnitude of contour
      interaction decreases systematically as luminance is reduced, from approximately
      a 50% reduction to a 30% reduction in percent correct. The constant angular
      extent and decreasing magnitude of contour interaction with a reduction of
      background luminance suggest foveal contour interaction is mediated by luminance
      dependent lateral inhibition within a fixed angular region.

PMID- 23880126
TI  - Mental health services in new Libya: the way forward.

PMID- 23880127
TI  - Plants traditionally used individually and in combination to treat sexually
      transmitted infections in northern Maputaland, South Africa: antimicrobial
      activity and cytotoxicity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Although medicinal plants are used extensively to
      treat sexually transmitted infections (STIs) in rural northern Maputaland,
      KwaZulu-Natal, the efficacy and safety of these plants have not previously been
      evaluated. AIM OF STUDY: A study was designed to investigate the in vitro
      antimicrobial activity and cytotoxicity profiles of a selection (individual
      plants and selected combinations) of traditionally used plants in this study
      area. MATERIALS AND METHODS: Aqueous and organic (dichloromethane: methanol, 1:1)
      extracts were prepared. Antimicrobial activity was assessed using the minimum
      inhibitory concentration (MIC) assay against the STI associated pathogens;
      Candida albicans ATCC 10231, Ureaplasma urealyticum clinical strain, Oligella
      ureolytica ATCC 43534, Trichomonas vaginalis clinical strain, Gardnerella
      vaginalis ATCC 14018 and Neisseria gonorrhoeae ATCC 19424. For the combination
      study, interactions were assessed using the fractional inhibitory concentration
      (SigmaFIC). The plant species were assessed for safety using the 3-[4,5-dimethyl
      2-thiazol-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) cellular viability assay
      on the human embryonic kidney epithelial (Graham, HEK-293) cell line. RESULTS:
      For the antimicrobial studies, U. urealyticum was the most sensitive of the six
      test organisms, with the aqueous extract of Ranunculus multifidus (0.02mg/ml) and
      the organic extract of Peltophorum africanum (0.04mg/ml) being the most
      antimicrobially active plant species studied. Sclerocarya birrea was found to
      have the broadest spectrum of activity (mean MIC of 0.89mg/ml). The only plant
      species to exhibit some degree of cytotoxicity against the kidney epithelial cell
      line was Kigelia africana (100ug/ml), with 22% and 16% cell death for the aqueous
      and organic extracts, respectively. Of the 13 combinations studied, several
      synergistic combinations were evident, the most prominent being the combination
      of Albizia adianthifolia and Trichilia dregeana (aqueous extract) with an
      SigmaFIC value of 0.15 against O. ureolytica. Synergistic interactions were
      observed regardless of the ratio of the aqueous mixtures of the two plants.
      Syzygium cordatum and S. birrea (aqueous extract) was also a combination of
      interest, demonstrating synergistic (SigmaFIC=0.42) interactions against O.
      ureolytica. This combination, however, also displayed some cytotoxicity towards
      the human epithelial cell line. CONCLUSION: This study demonstrated that
      anecdotal evidence of plant use does not always correlate with in vitro activity.
      Furthermore, the toxicological profiling is of utmost importance as if not
      combined in its correct ratio can lead to potential adverse effects.

PMID- 23880128
TI  - How early to take arms against a sea of troubles? The case for aggressive early
      therapy in Crohn's disease to prevent fibrotic intestinal strictures.
AB  - While potent anti-inflammatory medications have reduced the symptoms of Crohn's
      disease, more than 60% of patients eventually require surgery due to the
      development of fibrosis. Even after the introduction of biologic drugs, the
      population-based rate of surgery for Crohn's disease has not decreased. We
      suspect this is due to late initiation of these therapies, after the fibrosis
      cascade is unstoppable. We review the evidence that suggests early aggressive
      therapy is beneficial, especially in patients diagnosed before age 40, and with
      ileal or perianal disease. Patients with symptomatic strictures may benefit from
      early surgery (before penetrating complications) followed by initiation of
      biologics. With increased early use of biologics and better control of
      inflammation, we hope to see a global reduction in intestinal fibrosis and
      related complications of Crohn's disease. 

PMID- 23880129
TI  - Effects of total ammonia nitrogen concentration on solid-state anaerobic
      digestion of corn stover.
AB  - The inhibitive effect of total ammonia nitrogen (TAN) (including NH3 and NH4(+))
      on solid-state anaerobic digestion of corn stover was investigated in batch
      reactors at 37 degrees C. The highest methane yield of 107.0 L/kg VS(feed) was
      obtained at a TAN concentration of 2.5 g/kg (based on total weight). TAN
      concentrations greater than 2.5 g/kg resulted in decreased methane yields, with a
      50% reduction observed at a concentration of 6.0 g/kg. Reduced reaction rates and
      microbial activities for hydrolysis of cellulose and methanogenesis from acetate
      were observed at TAN concentrations higher than 4.3 g/kg. Strong ammonia stress
      was indicated at butyrate concentrations higher than 300 mg/kg. Result showed
      that the effluent of liquid anaerobic digestion can provide enough nitrogen for
      solid-state anaerobic digestion of corn stover.

PMID- 23880130
TI  - CO2 gasification reactivity of biomass char: catalytic influence of alkali,
      alkaline earth and transition metal salts.
AB  - This study investigates the influence of alkali (Na, K), alkaline earth (Ca, Mg)
      and transition (Fe) metal nitrates on CO2 gasification reactivity of pistachio
      nut shell (PNS) char. The preliminary gasification experiments were performed in
      thermogravimetric analyzer (TGA) and the results showed considerable improvement
      in carbon conversion; Na-char>Ca-char>Fe-char>K-char>Mg-char>raw char. Based on
      TGA studies, NaNO3 (with loadings of 3-7 wt%) was selected as the superior
      catalyst for further gasification studies in bench-scale reactor; the highest
      reactivity was devoted to 5 wt% Na loaded char. The data acquired for
      gasification rate of catalyzed char were fitted with several kinetic models,
      among which, random pore model was adopted as the best model. Based on obtained
      gasification rate constant and using the Arrhenius plot, activation energy of 5
      wt% Na loaded char was calculated as 151.46 kJ/mol which was 53 kJ/mol lower than
      that of un-catalyzed char.

PMID- 23880131
TI  - Net energy production and emissions mitigation of domestic wastewater treatment
      system: a comparison of different biogas-sludge use alternatives.
AB  - Wastewater treatment systems are increasingly designed for the recovery of
      valuable chemicals and energy in addition to waste stream disposal. Herein, the
      life-cycle energy production and emissions mitigation of a typical domestic
      wastewater treatment system were assessed, in which different combinations of
      biogas use and sludge processing lines for industrial or household applications
      were considered. The results suggested that the reuse of biogas and sludge was so
      important in the system's overall energy balance and environmental performance
      that it may offset the cost in the plant's installation and operation. Combined
      heat and power and household utilization were two prior options for net energy
      production, provided an ideal power conversion efficiency and biogas production.
      The joint application of household biogas use and sludge nutrient processing
      achieved both high net energy production and significant environmental
      remediation across all impact categories, representing the optimal tradeoff for
      domestic wastewater treatment. 

PMID- 23880132
TI  - Improving the flexibility of microbial desalination cells through spatially
      decoupling anode and cathode.
AB  - To improve the flexibility of microbial desalination cell (MDC) construction and
      operation, a new configuration with decoupled anode and cathode was developed and
      examined in this study. A higher salt concentration resulted in higher current
      generation, as well as a higher salt removal rate. The effect of the distance
      between the anode and the cathode on the MDC performance was not obvious, likely
      due to a sufficient conductivity in the salt solution. Because the cathode was
      identified as a limiting factor, adding one more cathode unit increased the
      current generation from 72.3 to 116.0 A/m(3), while installing additional anode
      units did not obviously alter the MDC current production. Changing the position
      of the anode/cathode units exhibited a weak influence on the MDC performance.
      Parallel connection of electrical circuits generally produced more current than
      the individual connections, and a strong competition was observed between
      multiple units sharing the same opposite unit.

PMID- 23880134
TI  - The DSM-5 approach to psychotic disorders: is it possible to overcome the
      'inherent conservative bias'?

PMID- 23880133
TI  - Mathematical modelling of spatio-temporal glioma evolution.
AB  - BACKGROUND: Gliomas are the most common types of brain cancer, well known for
      their aggressive proliferation and the invasive behavior leading to a high
      mortality rate. Several mathematical models have been developed for identifying
      the interactions between glioma cells and tissue microenvironment, which play an
      important role in the mechanism of the tumor formation and progression. METHODS:
      Building and expanding on existing approaches, this paper develops a continuous
      three-dimensional model of avascular glioma spatio-temporal evolution. The
      proposed spherical model incorporates the interactions between the populations of
      four different glioma cell phenotypes (proliferative, hypoxic, hypoglychemic and
      necrotic) and their tissue microenvironment, in order to investigate how they
      affect tumor growth and invasion in an isotropic and homogeneous medium. The
      model includes two key variables involved in the proliferation and invasion
      processes of cancer cells; i.e. the extracellular matrix and the matrix
      degradative enzymes concentrations inside the tumor and its surroundings.
      Additionally, the proposed model focuses on innovative features, such as the
      separate and independent impact of two vital nutrients, namely oxygen and
      glucose, in tumor growth, leading to the formation of cell populations with
      different metabolic profiles. The model implementation takes under consideration
      the variations of particular factors, such as the local cell proliferation rate,
      the variable conversion rates of cells from one category to another and the
      nutrient-dependent thresholds of conversion. All model variables (cell densities,
      ingredients concentrations) are continuous and described by reaction-diffusion
      equations. RESULTS: Several simulations were performed using combinations of
      growth and invasion rates, for different evolution times. The model results were
      evaluated by medical experts and validated on experimental glioma models
      available in the literature, revealing high agreement between simulated and
      experimental results. CONCLUSIONS: Based on the experimental validation, as well
      as the evaluation by clinical experts, the proposed model may provide an
      essential tool for the patient-specific simulation of different tumor evolution
      scenarios and reliable prognosis of glioma spatio-temporal progression.

PMID- 23880135
TI  - Colonic bacterial metabolites and human health.
AB  - The influence of the microbial-mammalian metabolic axis is becoming increasingly
      important for human health. Bacterial fermentation of carbohydrates (CHOs) and
      proteins produces short-chain fatty acids (SCFA) and a range of other metabolites
      including those from aromatic amino acid (AAA) fermentation. SCFA influence host
      health as energy sources and via multiple signalling mechanisms. Bacterial
      transformation of fibre-related phytochemicals is associated with a reduced
      incidence of several chronic diseases. The 'gut-liver axis' is an emerging area
      of study. Microbial deconjugation of xenobiotics and release of aromatic moieties
      into the colon can have a wide range of physiological consequences. In addition,
      the role of the gut microbiota in choline deficiency in non-alcoholic fatty liver
      disease (NAFLD) and insulin resistance is receiving increased attention. 

PMID- 23880136
TI  - Bacterial biofilm development as a multicellular adaptation: antibiotic
      resistance and new therapeutic strategies.
AB  - Bacteria have evolved the ability to form multicellular, surface-adherent
      communities called biofilms that allow survival in hostile environments. In
      clinical settings, bacteria are exposed to various sources of stress, including
      antibiotics, nutrient limitation, anaerobiosis, heat shock, etc., which in turn
      trigger adaptive responses in bacterial cells. The combination of this and other
      defense mechanisms results in the formation of highly (adaptively) resistant
      multicellular structures that are recalcitrant to host immune clearance
      mechanisms and very difficult to eradicate with the currently available
      antimicrobial agents, which are generally developed for the eradication of free
      swimming (planktonic) bacteria. However, novel strategies that specifically
      target the biofilm mode of growth have been recently described, thus providing
      the basis for future anti-biofilm therapy. 

PMID- 23880137
TI  - Innate immunity, the constant gardener of antimicrobial defense.

PMID- 23880138
TI  - Impact of aging on long-term ocular reflex adaptation.
AB  - Compensatory eye movements (CEMs) stabilize the field of view enabling visual
      sharpness despite self-induced motion or environmental perturbations. The
      vestibulocerebellum makes it possible to adapt these reflex behaviors to perform
      optimally under novel circumstances that are sustained over time. Because of this
      and the fact that the eye is relatively insensitive to fatigue and
      musculoskeletal aging effects, CEMs form an ideal motor system to assess aging
      effects on cerebellar motor learning. In the present study, we performed an
      extensive behavioral examination of the impact of aging on both basic CEMs and
      oculomotor-based learning paradigms spanning multiple days. Our data show that
      healthy aging has little to no effect on basic CEM performance despite sensory
      deterioration, suggesting a central compensatory mechanism. Young mice are
      capable of adapting their oculomotor output to novel conditions rapidly and
      accurately, even to the point of reversing the direction of the reflex entirely.
      However, oculomotor learning and consolidation capabilities show a progressive
      decay as age increases. 

PMID- 23880140
TI  - Does TP53 mutation promote ovarian cancer metastasis to omentum by regulating
      lipid metabolism?
AB  - TP53 (Tumor Protein 53, previously known as p53) is probably the best known of
      all tumor suppressor genes, and is mutated in nearly all (96%) high-grade serous
      ovarian cancer (HGS-OvCa), which is the most common histopathological type of
      epithelial ovarian cancer (EOC). Recently, TP53 is found to involve in regulating
      cell metabolic pathways besides its classical tumor suppressive functions. In
      addition, emerging evidence suggests that mutant TP53 is associated with cancer
      metastasis. Through summarizing and comparing the roles of wild-type TP53 and
      mutant TP53 in the progression of various types of cancer, we hypothesize that
      mutant TP53 in HGS-OvCa cells interacts with sterol regulatory element-binding
      proteins (SREBPs) and guanidinoacetate N-methyltransferase (GAMT), leading to
      increased gene expression of key enzymes involved in fatty acids (FAs) and
      cholesterol biosynthesis and the inhibition of fatty acid oxidation (FAO), thus
      promotes lipid anabolism to accelerate tumor growth and progression. Elevated
      platelet number in patients' tumor microenvironment results in increased TGF-beta
      production. Then, TGF-beta acts in concert with mutant TP53 to promote HGS-OvCa
      metastasis by assembling a mutant-TP53/p63/Smads protein complex, in which p63's
      functions as metastasis suppressor are antagonized, and by enhancing the
      activities of the Slug/Snail and Twist families to drive induce EMT-like
      transition. Then adipocyte-derived IL-8 facilitates the metastasis of
      transformative cancer cells to abdominal adipose tissue (e.g., omentum). Once
      metastasis is established, mutant TP53 together with adipocyte-derived IL-8
      upregulates Fatty acid-binding protein 4 (FABP4) expression and then promotes FAs
      absorption from adipocytes to support rapid tumor growth in adipocyte-rich
      metastatic environments. In summary, these indicate that mutant TP53 may play
      determinant roles in the progression of HGS-OvCa. 

PMID- 23880141
TI  - Could more than three million older people in England be at risk of alcohol
      related harm? A cross-sectional analysis of proposed age-specific drinking
      limits.
AB  - OBJECTIVE: to determine the impact of recently proposed age-specific alcohol
      consumption limits on the proportion and number of older people classified at
      risk of alcohol-related harm. DESIGN: nationally representative cross-sectional
      population data from the Health Survey for England (HSE). PARTICIPANTS: adults
      with valid alcohol consumption data, comprising 14,718 participants from 2003 and
      14,939 from 2008. MAIN OUTCOME MEASURE: the prevalence of alcohol consumption in
      excess of existing and recently proposed consumption limits, plus associated
      population estimates. RESULTS: the number of individuals aged 65 or over and
      drinking in excess of daily recommended limits would have increased 2.5-fold to
      over 3 million in 2008 under age-specific recommendations proposed in a report
      from the Royal College of Psychiatrists, equating to an at-risk population
      809,000 individuals greater than found within the 16-24 age group during the same
      year. Suggested revisions to existing binge drinking classifications would have
      defined almost 1,200,000 people aged 65 or over as hazardous consumers of alcohol
      in 2008-a 3.6-fold increase over existing definitions. CONCLUSION: age-specific
      drinking recommendations proposed in the Royal College of Psychiatrists Report
      would increase the number of older drinkers classified as hazardous alcohol
      consumers to a level greater than found among young adults aged 16-24.

PMID- 23880139
TI  - Increased micro-RNA 29b in the aged brain correlates with the reduction of
      insulin-like growth factor-1 and fractalkine ligand.
AB  - Microglia develop an inflammatory phenotype during normal aging. The mechanism by
      which this occurs is not well understood, but might be related to impairments in
      several key immunoregulatory systems. Here we show that micro-RNA (miR)-29a and
      miR-29b, 2 immunoregulatory micro-RNAs, were increased in the brain of aged
      BALB/c mice compared with adults. Insulin-like growth factor-1 (IGF-1) and
      fractalkine ligand (CX3CL1) are negative modulators of microglial activation and
      were identified as targets of miR-29a and miR-29b using luciferase assay and
      primary microglia transfection. Indeed, higher expression of miR-29b in the brain
      of aged mice was associated with reduced messenger RNA (mRNA) levels of IGF-1 and
      CX3CL1. Parallel to these results in mice, miR-29a and miR-29b were also markedly
      increased in cortical brain tissue of older individuals (mean, 77 years) compared
      with middle-aged adults (mean, 45 years). Moreover, increased expression of miR
      29b in human cortical tissue was negatively correlated with IGF-1 and CX3CL1
      expression. Collectively, these data indicate that an age-associated increase in
      miR-29 corresponded with the reduction of 2 important regulators of microglia,
      IGF-1 and CX3CL1. 

PMID- 23880142
TI  - The incidence of Parkinson's disease in the North-East of England.
AB  - BACKGROUND: Parkinson's disease is a common disorder among older people. Accurate
      epidemiological information is essential to identify possible aetiological
      factors, plan health services and set priorities for medical research. OBJECTIVE:
      to determine the incidence of idiopathic Parkinson's disease in a defined
      geographical area in the North-East of England. METHODS: using a prospective,
      longitudinal design, we sought to identify every new case of Parkinson's disease
      arising in the Newcastle and Gateshead area in the North-East of England. The
      base population comprised 488 576 individuals and multiple sources of case
      ascertainment were employed. All the patients with newly diagnosed idiopathic
      Parkinson's disease or parkinsonism between 1 June 2009 and 31 May 2011 were
      invited to participate. Patients were examined by a specialist and followed
      longitudinally to permit diagnostic review. RESULTS: we identified 257 potential
      cases, of whom 181 had suspected idiopathic Parkinson's disease. After a follow
      up period of 18 months, 155 patients retained a clinical diagnosis of probable
      Parkinson's disease. The mean age at diagnosis was 72.4 +/- 10 years. The crude
      incidence of PD in Newcastle and Gateshead was 15.9 per 100 000 persons per year
      (95% CI: 13.4-18.4). Age-standardised to the European population the incidence of
      Parkinson's disease was 12.0 per 100 000 (95% CI: 10.1-14.0). We found a higher
      crude incidence among men 17.7 per 100 000 (95% CI: 14.0-21.4) than women 14.0
      per 100 000 (95% CI: 10.7-17.4). CONCLUSION: in this prospective longitudinal
      study, the incidence rate of Parkinson's disease in North-East England is similar
      to that of other modern European and American studies.

PMID- 23880143
TI  - A controlled evaluation of comprehensive geriatric assessment in the emergency
      department: the 'Emergency Frailty Unit'.
AB  - BACKGROUND: the ageing demographic means that increasing numbers of older people
      will be attending emergency departments (EDs). Little previous research has
      focused on the needs of older people in ED and there have been no evaluations of
      comprehensive geriatric assessment (CGA) embedded within the ED setting. METHODS:
      a pre-post cohort study of the impact of embedding CGA within a large ED in the
      East Midlands, UK. The primary outcome was admission avoidance from the ED, with
      readmissions, length of stay and bed-day use as secondary outcomes. RESULTS:
      attendances to ED increased in older people over the study period, whereas the ED
      conversion rate fell from 69.6 to 61.2% in people aged 85+, and readmission rates
      in this group fell from 26.0% at 90 days to 19.9%. In-patient bed-day use
      increased slightly, as did the mean length of stay. DISCUSSION: it is possible to
      embed CGA within EDs, which is associated with improvements in operational
      outcomes.

PMID- 23880144
TI  - Dynamic expression of neurexophilin1 during zebrafish embryonic development.
AB  - Neurexophilin 1 (Nxph1) is a specific endoligand of alpha-neurexins that is
      essential for trans-synaptic activation. Here, we report its dynamic expression
      during development in zebrafish. Our study revealed an early onset of expression
      of nxph1. RT-PCR on a series of embryonic stages showed that it is maternally
      deposited, although only readily detectable by whole mount in situ hybridization
      by 22hpf. During embryogenesis and larval stages, the zygotic transcript is
      expressed dynamically in various clusters of post-mitotic neurons and in glia in
      the central nervous system. 

PMID- 23880145
TI  - Plasma gelsolin levels and outcomes after aneurysmal subarachnoid hemorrhage.
AB  - INTRODUCTION: Lower gelsolin levels have been associated with the severity and
      poor outcome of critical illness. Nevertheless, their link with clinical outcomes
      of aneurysmal subarachnoid hemorrhage is unknown. Therefore, we aimed to
      investigate the relationship between plasma gelsolin levels and clinical outcomes
      in patients with aneurysmal subarachnoid hemorrhage. METHODS: A total of 262
      consecutive patients and 150 healthy subjects were included. Plasma gelsolin
      levels were measured by enzyme-linked immunosorbent assay. Mortality and poor
      long-term outcome (Glasgow Outcome Scale score of 1-3) at 6 months were recorded.
      RESULTS: Plasma gelsolin levels on admission were substantially lower in patients
      than in healthy controls (66.9 (26.4) mg/L vs. 126.4 (35.4) mg/L, P < 0.001), and
      negatively associated with World Federation of Neurological Surgeons score (r = 
      0.554, P < 0.001) and Fisher score (r = -0.538, P < 0.001), and identified as an
      independent predictor of poor functional outcome (odds ratio, 0.957; 95%
      confidence interval (CI), 0.933-0.983; P = 0.001) and death (odds ratio, 0.953;
      95% CI, 0.917-0.990; P = 0.003) after 6 months. The areas under the ROC curve of
      gelsolin for functional outcome and mortality were similar to those of World
      Federation of Neurological Surgeons score and Fisher score (all P > 0.05).
      Gelsolin improved the predictive values of World Federation of Neurological
      Surgeons score and Fisher score for functional outcome (both P < 0.05), but not
      for mortality (both P > 0.05). CONCLUSIONS: Gelsolin levels are a useful,
      complementary tool to predict functional outcome and mortality 6 months after
      aneurysmal subarachnoid hemorrhage.

PMID- 23880146
TI  - Significant changes in integrase-associated HIV-1 replication capacity between
      early and late isolates.
AB  - During the human immunodeficiency virus type 1 (HIV-1) pandemic, continuous,
      extensive genetic diversification of the virus has been observed. To study the
      effect of HIV-1 diversification on integrase-associated viral replication
      capacity (RC), 94 HIV-1 subtype B integrase sequences from two groups of
      antiretroviral-naive viruses isolated 15 y apart were amplified and recombined
      with an HIV-1 infectious clone. Viral RC was determined by infecting a T cell
      line with a long terminal repeat-driven green fluorescent protein reporter.
      Significant differences in integrase-mediated RC were observed between
      recombinant viruses from early and late isolates (p=0.0286). Integrases from late
      isolates had significantly lower sequence conservation scores compared to an
      ancestral subtype B sequence (p<0.0001). Integrase amino acid polymorphisms S17N,
      I72V, S119P, and D256E were associated with a lower ex vivo viral RC. These
      results suggest that integrase sequence diversification has affected ex vivo HIV
      1 RC. 

PMID- 23880147
TI  - Are prognostic factors more favorable for breast cancer detected by organized
      screening than by opportunistic screening or clinical diagnosis? A study in Loire
      Atlantique (France).
AB  - PURPOSE: Comparisons of breast cancer characteristics between organized and
      opportunistic screening have been limited. This study was designed to compare
      characteristics of cancers detected by either organized or opportunistic
      screening as well as clinically diagnosed cancers in Loire-Atlantique (a French
      administrative entity), from 2003 to 2007. METHODS: This study is based on data
      from the population-based Loire-Atlantique Cancer Registry. Stage at diagnosis
      and prognostic characteristics of carcinomas detected by organized screening were
      compared, by age-adjusted logistic regressions, to those of cancers detected by
      opportunistic screening and diagnosed clinically. Analyses were restricted to
      women aged 50-74 years (the age group targeted by the organized screening
      program) for the 2003-2007 period. RESULTS: Between 2003 and 2007, 2864 invasive
      and 400 in situ breast cancer cases were diagnosed in women aged 50-74 years in
      Loire-Atlantique. Compared to cancers diagnosed clinically, cancers detected by
      organized screening were more likely to be in situ (13.7% vs. 3.8%), diagnosed at
      an early stage (74.4% vs. 51.3%), have a low SBR grade (grade 1: 35.4% vs.
      18.5%), and be positive for estrogen-progesterone receptors (68.3% vs. 59.0%).
      The distribution of stage at diagnosis and prognostic characteristics between
      organized and opportunistic screening were similar. CONCLUSION: These findings
      are consistent with the hypothesis that breast cancers are detected early by
      organized screening. Cancer characteristics were similar between the two
      screening modes. Estimating the impact of mammography screening on mortality in
      Loire-Atlantique should be the object of further investigations.

PMID- 23880148
TI  - The effect of home-based cardiac rehabilitation program on self efficacy of
      patients referred to cardiac rehabilitation center.
AB  - BACKGROUND: The prevalence of coronary heart disease is increasing worldwide
      contributing to mortality and morbidity of millions of people. Cardiac
      rehabilitation is an interdisciplinary activity with the aim of facilitating and
      improving the physical, psychological and emotional state of the patients with
      cardiac complications. This study aimed to evaluate the probable positive effects
      of continuing cardiac rehabilitation programs at home on self-efficacy of the
      patients with cardiac complications. METHOD: In a randomized controlled trial, 80
      patients referred to rehabilitation center from Feb 2009 to Jan 2010 were
      randomly divided into case and control groups. Both groups received routine
      cardiac rehabilitation programs in the rehabilitation center. In addition, the
      case group received education and practical training in various rehabilitation
      measures along with home visits of a community health nurse throughout the follow
      up period. General Self Efficacy Scale (GSES) was used to assess self-efficacy
      between two groups at baseline and follow-up periods. Collected data from GSES
      questionnaires were analyzed using Minitab software and repeated measurement
      analysis model. RESULTS: No first time (before beginning of rehabilitation
      program) GESE differences were observed between case (26.36 +/- 0.84) and control
      (28.53 +/- 0.54) groups (P = 0.44). In the final measurement, GESE in case group
      was 36.59 +/- 5.65 vs. 26.5 +/- 0.91 in the control group. There was a
      statistically significant difference in self-efficacy between two groups and in
      different measurements (P = 0.000). CONCLUSION: Home-based cardiac rehabilitation
      has a positive effect on patients' self-efficacy and therefore it is recommended
      for the patients suffering from heart diseases. TRIAL REGISTRATION: RCT
      registration number: IRCT201106086747N1.

PMID- 23880149
TI  - Documenting clinical performance problems among medical students: feedback for
      learner remediation and curriculum enhancement.
AB  - INTRODUCTION: We operationalized the taxonomy developed by Hauer and colleagues
      describing common clinical performance problems. Faculty raters pilot tested the
      resulting worksheet by observing recordings of problematic simulated clinical
      encounters involving third-year medical students. This approach provided a
      framework for structured feedback to guide learner improvement and curricular
      enhancement. METHODS: Eighty-two problematic clinical encounters from M3 students
      who failed their clinical competency examination were independently rated by
      paired clinical faculty members to identify common problems related to the
      medical interview, physical examination, and professionalism. RESULTS: Eleven out
      of 26 target performance problems were present in 25% or more encounters.
      Overall, 37% had unsatisfactory medical interviews, with 'inadequate history to
      rule out other diagnoses' most prevalent (60%). Seventy percent failed because of
      physical examination deficiencies, with missing elements (69%) and inadequate
      data gathering (69%) most common. One-third of the students did not introduce
      themselves to their patients. Among students failing based on standardized
      patient (SP) ratings, 93% also failed to demonstrate competency based on the
      faculty ratings. CONCLUSIONS: Our review form allowed clinical faculty to
      validate pass/fail decisions based on standardized patient ratings. Detailed
      information about performance problems contributes to learner feedback and
      curricular enhancement to guide remediation planning and faculty development.

PMID- 23880150
TI  - Severe airway obstruction from a bronchial cast after cardiac transplantation.
AB  - Plastic bronchitis is a rare and difficult to treat disease process in patients
      with congenital heart disease. Cardiac transplantation has been used increasingly
      to reverse this process, especially in single ventricle physiology. This case
      report demonstrates a foreseeable complication after cardiac transplantation in
      such a patient. 

PMID- 23880151
TI  - Self-collection for high-risk HPV detection in Brazilian women using the
      careHPVTM test.
AB  - OBJECTIVE: Cervical cancer is the second most common cancer among Brazilian
      women. High-risk human papillomavirus (hr-HPV) persistence is the primary cause
      of cervical neoplasia. Early detection of hr-HPV is important for identifying
      women at risk for developing cervical lesions. Approximately 85% of new cases of
      cervical cancer worldwide and 50% of the total cervical cancer deaths occurred in
      developing countries. Here, a new methodology to support a cervical cancer
      screening program was evaluated in women from various Brazilian regions. METHODS:
      Two thousand women aged 18-77 years were enrolled in an opportunistic cervical
      cancer screening program and were randomized into self-vaginal or health
      professional-guided cervical sampling groups. The Qiagen careHPVTM test was
      performed on all samples. Pap tests were performed on all women using liquid
      based cytology. RESULTS: Positive hr-HPV results were obtained in 12.3%
      (245/2000) of women; similar rates were observed in self- or health professional
      collected samples. Eighty-nine percent (1719/2000) of cervical cytologies
      classified as normal were negative to hr-HPV. Among the cytological samples,
      36.6% classified as ASC-US+ were positive to hr-HPV, 78.8% were LSIL and 75.0%
      were HSIL. CONCLUSIONS: Self-sampled and health professional-sampled
      vaginal/cervical specimens did not differ in their rates of detection of hr-HPV.
      Therefore, HPV DNA testing in self-sampled vaginal cells is an alternative to
      primary screening in low-resource settings.

PMID- 23880153
TI  - Approaching suspicious lymph nodes on the upper abdomen in gynecologic oncology.

PMID- 23880152
TI  - Abdominopelvic cytoreduction rates and recurrence sites in stage IV ovarian
      cancer: is there a case for thoracic cytoreduction?
AB  - OBJECTIVE: We report the rates of optimal abdominopelvic cytoreduction and the
      sites of recurrence in stage IV ovarian cancer patients, with particular
      attention to the potential impact of thoracic cytoreduction on treatment results
      in patients with intra-thoracic spread. METHODS: A historic cohort study of all
      stage IV ovarian cancer patients diagnosed between 1994 and 2010 and underwent
      abdominopelvic cytoreductive surgery. Controls were stage IIIc patients.
      Statistical analyses included chi(2) test, Cox proportional hazards regression
      models and Kaplan-Meier curves with log-rank tests. RESULTS: Group 1 included 76
      stage IV patients, 55% with thoracic spread. Group 2 included 142 stage IIIc
      patients. Age, histology, primary peritoneal tumor and ascites rates were similar
      for the two groups. Respective rates of optimal abdominopelvic cytoreduction were
      68% vs. 83.5% (p<0.05), median time to progression 5.3 vs. 12.3 months (p<0.01)
      and overall survival 27.2 vs. 46.1 months (p<0.01). Optimal cytoreduction and
      survival rates were similar for all group 1 patients regardless of spread
      location. Sites of recurrence in stage IV were abdomen (59.3%), thorax (6.8%),
      both (28.8%) or other (5.1%). The four patients with thoracic recurrence alone
      were all initially diagnosed with malignant pleural effusion. Three of them
      developed abdominal recurrence within 15-6 months. CONCLUSIONS: Optimal
      abdominopelvic cytoreduction was achievable in stage IV patients, although in
      significantly fewer patients than in stage IIIc. Sites of recurrence were rarely
      thorax alone, implying that thoracic debulking is likely to change the course of
      disease in only few patients and thus should be carefully individualized.

PMID- 23880154
TI  - Mode of delivery and adiposity: Hong Kong's "Children of 1997" birth cohort.
AB  - PURPOSE: To examine whether mode of delivery was associated with childhood
      adiposity in a developed non-Western context. METHODS: We used generalized
      estimating equations to estimate the association of mode of delivery (vaginal or
      cesarean) with body mass index (BMI) z-score and overweight (including obesity)
      from 3 months to 13 years, in 7809 term birth (94% follow-up) from a population
      representative Chinese birth cohort, "Children of 1997." We used multiple
      imputation for missing data. RESULTS: The cesarean section rate (26%) was higher
      for children born in private hospitals, with lower gestational age, lower birth
      order, higher maternal age, higher maternal BMI, and higher family socioeconomic
      position. Cesarean section was not associated with BMI z-score from 3 months to
      13 years (mean difference, 0.03; 95% confidence interval, -0.02 to 0.09) or
      overweight from 3 years to 13 years (odds ratio, 0.98; 95% confidence interval,
      0.77 to 1.25) after adjusting for infant and maternal characteristics and family
      socioeconomic position. CONCLUSIONS: In a non-Western developed setting, mode of
      delivery was not clearly associated with BMI or overweight (including obesity)
      into late childhood. From a public health perspective, the role of mode of
      delivery and its mechanistic pathway in the current burgeoning epidemic of
      obesity needs to be clarified.

PMID- 23880156
TI  - Does breastfeeding contribute to the racial gap in reading and math test scores?
AB  - PURPOSE: The aim of this study was to examine the impact of divergent
      breastfeeding practices between Caucasian and African American mothers on the
      lingering achievement test gap between Caucasian and African American children.
      METHODS: The Child Development Supplement of the Panel Study of Income Dynamics,
      beginning in 1997, followed a cohort of 3563 children aged 0-12 years. Reading
      and math test scores from 2002 for 1928 children were linked with breastfeeding
      history. Regression analysis was used to examine associations between ever having
      been breastfed and duration of breastfeeding and test scores, controlling for
      characteristics of child, mother, and household. RESULTS: African American
      students scored significantly lower than Caucasian children by 10.6 and 10.9
      points on reading and math tests, respectively. After accounting for the impact
      of having been breastfed during infancy, the racial test gap decreased by 17% for
      reading scores and 9% for math scores. CONCLUSIONS: Study findings indicate that
      breastfeeding explains 17% and 9% of the observed gaps in reading and math
      scores, respectively, between African Americans and Caucasians, an effect larger
      than most recent educational policy interventions. Renewed efforts around
      policies and clinical practices that promote and remove barriers for African
      American mothers to breastfeed should be implemented.

PMID- 23880155
TI  - Risk factors for pregnancy-associated breast cancer: a report from the Nigerian
      Breast Cancer Study.
AB  - PURPOSE: Little is known about risk factors for pregnancy-associated breast
      cancer (PABC), diagnosed during pregnancy or postpartum. METHODS: We enrolled
      1715 premenopausal women from the Nigerian Breast Cancer Study from 1998 to 2011.
      Based on recency of last pregnancy from diagnosis, breast cancer cases were
      categorized as (1) PABC diagnosed 2 years or longer postpartum, (2) PABC
      diagnosed 3 to 5 years postpartum, or (3) non-PABC diagnosed more than 5 years
      postpartum. Controls were matched to cases on recency of last pregnancy. Multiple
      logistic regressions were performed comparing cases and controls within each
      group. RESULTS: Of the 718 cases, 152 (21.2%) had PABC 2 or more years
      postpartum, and 145 (20.2%) 3 to 5 years postpartum. Although not statistically
      significant, women with higher parity tend to have an elevated risk of PABC but
      reduced risk of non-PABC (p for heterogeneity = 0.097). Family history of breast
      cancer might be a strong predictor particularly for PABC 2 or more years
      postpartum (odds ratio, 3.28; 95% confidence interval, 1.05-10.3). Compared with
      non-PABC cases, PABC 2 or more years postpartum cases were more likely to carry
      BRCA1/2 mutations (P = .03). CONCLUSIONS: Parity may have different roles in the
      development of PABC versus other premenopausal breast cancer in Nigerian women.
      Prospective mothers with multiple births and a family history of breast cancer
      may have an elevated risk of breast cancer during their immediate postpartum
      period.

PMID- 23880157
TI  - Acetylation at lysine 346 controls the transforming activity of the HTLV-1 Tax
      oncoprotein in the Rat-1 fibroblast model.
AB  - BACKGROUND: Transformation by the Tax oncoprotein of the human T cell leukemia
      virus type 1 (HTLV-1) is governed by actions on cellular regulatory signals,
      including modulation of specific cellular gene expression via activation of
      signaling pathways, acceleration of cell cycle progression via stimulation of
      cyclin-dependent kinase activity leading to retinoblastoma protein (pRb)
      hyperphosphorylation and perturbation of survival signals. These actions control
      early steps in T cell transformation and development of Adult T cell leukemia
      (ATL), an aggressive malignancy of HTLV-1 infected T lymphocytes. Post
      translational modifications of Tax by phosphorylation, ubiquitination,
      sumoylation and acetylation have been implicated in Tax-mediated activation of
      the NF-kappaB pathway, a key function associated with Tax transforming potential.
      RESULTS: In this study, we demonstrate that acetylation at lysine K(346) in the
      carboxy-terminal domain of Tax is modulated in the Tax nuclear bodies by the
      acetyltransferase p300 and the deacetylases HDAC5/7 and controls phosphorylation
      of the tumor suppressor pRb by Tax-cyclin D3-CDK4-p21(CIP) complexes. This
      property correlates with the inability of the acetylation deficient K(346)R
      mutant, but not the acetylation mimetic K(346)Q mutant, to promote anchorage
      independent growth of Rat-1 fibroblasts. By contrast, acetylation at lysine
      K(346) had no effects on the ability of Tax carboxy-terminal PDZ-binding domain
      to interact with the tumor suppressor hDLG. CONCLUSIONS: The identification of
      the acetyltransferase p300 and the deacetylase HDAC7 as enzymes modulating Tax
      acetylation points to new therapeutic targets for the treatment of HTLV-1
      infected patients at risk of developing ATL.

PMID- 23880158
TI  - Lipoic acid protects C6 cells against ammonia exposure through Na+-K+-Cl- co
      transporter and PKC pathway.
AB  - Astrocytes play an essential role in the central nervous system (CNS)
      homeostasis. They providing metabolic support and protecting against oxidative
      stress and glutamatergic excitotoxicity. Glutamate uptake, an electrogenic
      function, is driven by cation gradients and the Na+-K+-Cl- co-transporter (NKCC1)
      carries these ions into and out of the cell. Elevated concentrations of ammonia
      in the brain lead to cerebral dysfunction. Ammonia toxicity can be mediated by an
      excitotoxic mechanism, oxidative stress and ion discharged. Astrocytes also
      convert excess ammonia and glutamate into glutamine, via glutamine synthetase
      (GS). Lipoic acid (LA) is a modulator of the cellular redox status potentially
      beneficial in neurodegenerative diseases. In this study, we investigated the
      effect of LA on glial parameters, in C6 cells exposed to ammonia. Ammonia
      increased S100B secretion and decreased glutamate uptake, GS activity and
      glutathione (GSH) content. LA was able to prevent these effects. LA exerts its
      protective effect on glutamate uptake and S100B secretion via mechanisms
      dependent of NKCC1 and PKC. These findings show that LA is able to modulate glial
      function impairments by ammonia in vitro, indicating a potential therapeutic
      agent to improve glutamatergic metabolism and oxidative stress against
      hyperammonemia.

PMID- 23880160
TI  - Rapid detection of a norovirus pseudo-outbreak by using real-time sequence based
      information.
AB  - BACKGROUND: Sequence based information is increasingly used to study the
      epidemiology of viruses, not only to provide insight in viral evolution, but also
      to understand transmission patterns during outbreaks. However, sequence analysis
      is not yet routinely performed by diagnostic laboratories, limiting its use in
      clinical practice. OBJECTIVES: To describe the added value of sequence based
      information available within 3 days after the detection of norovirus in fecal
      samples of patients and personnel during a suspected outbreak on a hospital ward.
      Results were used to guide the implementation of appropriate infection control
      measures, in particular closure of the ward. STUDY DESIGN: Observational study.
      RESULTS: Norovirus infection was detected in seven patients and two health care
      workers on an oncology ward of the children's hospital. Six of seven patients had
      a hospital acquired infection defined as a first day of illness more than two
      days after admission. After notification of the first two patients, supplementary
      infection control measures were taken to prevent further spread. Despite these
      measures, three additional patients with norovirus infection were identified.
      Characterization of the noroviruses of 5 out of 7 patients was available within 7
      days after the notification of the first patient. Four different genotypes were
      detected, providing evidence for multiple introductions of different norovirus
      strains with only a few secondary cases rather than ongoing nosocomial
      transmission. Therefore, we maintained the already implemented infection control
      interventions without closure of the ward. CONCLUSIONS: Sequence based
      information available in real-time is helpful for understanding norovirus
      transmission in the hospital and facilitates appropriate infection control
      measures during an outbreak.

PMID- 23880159
TI  - Automated, simple, and efficient influenza RNA extraction from clinical
      respiratory swabs using TruTip and epMotion.
AB  - BACKGROUND: Rapid, simple and efficient influenza RNA purification from clinical
      samples is essential for sensitive molecular detection of influenza infection.
      Automation of the TruTip extraction method can increase sample throughput while
      maintaining performance. OBJECTIVES: To automate TruTip influenza RNA extraction
      using an Eppendorf epMotion robotic liquid handler, and to compare its
      performance to the bioMerieux easyMAG and Qiagen QIAcube instruments. STUDY
      DESIGN: Extraction efficacy and reproducibility of the automated TruTip/epMotion
      protocol was assessed from influenza-negative respiratory samples spiked with
      influenza A and B viruses. Clinical extraction performance from 170 influenza A
      and B-positive respiratory swabs was also evaluated and compared using influenza
      A and B real-time RT-PCR assays. RESULTS: TruTip/epMotion extraction efficacy was
      100% in influenza virus-spiked samples with at least 745 influenza A and 370
      influenza B input gene copies per extraction, and exhibited high reproducibility
      over four log10 concentrations of virus (<1% CV). RNA yields between the three
      automated methods differed by less than 0.5 log10 gene copies. 99% of clinical
      specimens that were PCR-positive after easyMAG or QIAcube extraction were also
      positive following TruTip extraction. Overall Ct value differences obtained
      between TruTip/epMotion and easyMAG/QIAcube clinical extracts ranged from 1.24 to
      1.91. Pairwise comparisons of Ct values showed a high correlation of the
      TruTip/epMotion protocol to the other methods (R2>0.90). CONCLUSION: The
      automated TruTip/epMotion protocol is a simple and rapid extraction method that
      reproducibly purifies influenza RNA from respiratory swabs, with comparable
      efficacy and efficiency to both the easyMAG and QIAcube instruments.

PMID- 23880161
TI  - Evaluation of genital self-sampling methods for HPV detection in males.
AB  - BACKGROUND: There are no population-based HPV prevalence estimates in males
      because optimal sampling methods are unclear. OBJECTIVES: To evaluate the
      acceptability, feasibility, and validity of different male genital self-sampling
      methods for HPV detection. STUDY DESIGN: A total of 450 males, 14-59 years old,
      were randomly assigned to one of three genital sampling methods: (1) dry
      polyester-tipped swab; (2) dry foam swab; and (3) emery paper and wetted
      polyester-tipped swab. Samples were both self-collected and collected by a
      clinician. Subjects were queried on the acceptability of sampling methods. HPV
      was genotyped using an L1 consensus PCR assay. RESULTS: Specimen adequacy (92
      96%, p=0.28) and HPV detection (44-49%, p=0.68) were comparable across the three
      methods. Concordance for HPV detection was observed between self- and clinician
      collected specimen pairs for all methods (kappa=0.70-0.80). The collection
      procedure was reported to be very easy by 69% of dry polyester-tipped swab users
      and 64% of dry foam swab users compared to 48% of emery-wet swab users (p=0.004).
      Similarly, 43-44% of dry swab and foam users reported the collection to be very
      comfortable compared to 24% of emery-wet swab users (p=0.002). Pain was reported
      by 10% of emery-wet swab users compared to 3% and 5% of dry swab and foam users,
      respectively (p=0.03). Self-collection by the emery-wet swab method required an
      average of 6 min compared to 3.3-3.5 min for the two dry methods (p<0.0001).
      CONCLUSIONS: The dry collection methods are optimal for use in large
      epidemiologic studies or surveillance efforts based on their acceptability and
      feasibility.

PMID- 23880162
TI  - Nucleoside plus nucleotide analogs and cessation of hepatitis B immunoglobulin
      after liver transplantation in chronic hepatitis B is safe and effective.
AB  - BACKGROUND: After orthotopic liver transplantation (OLT) in chronic hepatitis B
      (HBV), adequate prophylaxis for recurrence of HBV in the graft is mandatory.
      OBJECTIVES: Evaluate safety of HBV prophylaxis with tenofovir and emtricitabine
      (TDF/FTC) after cessation of hepatitis B immunoglobulin (HBIG) after OLT in
      chronic HBV. STUDY DESIGN: In 17 consecutive patients after OLT in chronic HBV we
      started TDF/FTC after cessation of HBIG. All had received HBIG >6 months. 15/17
      were HBsAg negative and 16/17 had undetectable HBV-DNA. RESULTS: After mean
      follow-up of 2 years 16/17 patients were alive, one died due to urosepsis. All 16
      with undetectable HBV-DNA remained HBV-DNA negative. From 15 HBsAg negative
      patients at start, in one seroconversion to positive HBsAg occurred, without
      detectable HBV-DNA. Liver biochemistry remained within the normal ranges. There
      were no cases of drug discontinuation. No major side effects were reported.
      TDF/FTC use saves ?16,262/year over standard-of-care (HBIG+LAM). This prospective
      follow-up study shows that in liver transplantation for chronic hepatitis B,
      after initial treatment including HBIG for at least 6 months combined with or
      followed by (dual) nucleos(t)ide analog therapy, TDF/FTC provides adequate
      prophylaxis against recurrent HBV infection without major side effects and leads
      to substantial cost savings over a regimen with HBIG. CONCLUSION: Combined
      prophylaxis with TDF/ETV nucleoside plus nucleotide analogs and cessation of
      immunoglobulin after liver transplantation in chronic hepatitis B is safe and
      effective.

PMID- 23880163
TI  - Lipoprotein lipase in non-small cell lung cancer tissue is highly expressed in a
      subpopulation of tumor-associated macrophages.
AB  - High lipoprotein lipase (LPL) activity in non-small cell lung cancer (NSCLC)
      tissue strongly predicts shorter patient survival. We tested the hypothesis that
      in NSCLC tissue, macrophages are the major site of LPL expression. LPL expression
      in the entire NSCLC tissue and in the adjacent non-cancer lung tissue was
      compared to the expression of genes preferentially expressed in macrophages. LPL
      expression at the cellular level was analyzed by mRNA fluorescence in situ
      hybridization. In the whole cancer tissue (but not in the adjacent non-cancer
      tissue), expression of LPL correlated with expression of genes preferentially
      expressed in macrophages (MSR1, CD163, FOLR2), but not with expression of genes
      preferentially expressed in tumor cells. All cells in the cancer and adjacent non
      cancer tissue exhibit low LPL expression. However, in cancer tissue only, there
      were individual highly LPL-expressing cells which were macrophages. These LPL
      overexpressing cells were approximately 10 times less abundant than anti-CD163
      stained, tumor-associated macrophages. To conclude, in NSCLC tissue, a
      subpopulation of tumor-associated macrophages highly expresses LPL. Because tumor
      associated macrophages are pro-tumorigenic, these cells should be further
      characterized to better understand the underlying nature of the close
      relationship between high LPL activity in NSCLC tissue and shorter patient
      survival. 

PMID- 23880164
TI  - Nuclear PKM2 expression predicts poor prognosis in patients with esophageal
      squamous cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors
      worldwide, with a high malignant degree and poor prognosis. The present study
      aims to investigate the relationship between pyruvate kinase M2 (PKM2) expression
      and the prognosis of patients with ESCC. The expression of PKM2 in 86 cases of
      esophageal carcinoma tissues was tested using immunohistochemistry. The
      relationship between PKM2 expression and clinical pathological parameters, and
      their effects on the prognosis of patients with ESCC were analyzed. The
      expression levels of PKM2 in both cytoplasm and nucleus of ESCC tissues were
      significantly higher than those in paracancerous tissues (P=6.73*10(-9) and
      4.32*10(-6), respectively). The Kaplan-Meier analysis showed that nuclear PKM2
      expression was closely related to the survival of patients with ESCC (P=0.005).
      Patients with high PKM2 expression in the nucleus had significantly shorter
      survival times than those with low PKM2 expression in the nucleus (hazard ratio
      for death, 2.358; 95% confidence interval, 1.156-4.812; P=0.018). No other
      significant difference was found between PMK2 expression and clinico-pathological
      features of ESCC patients (all P>0.05). In conclusion, high PKM2 expression in
      the nucleus is essential in the pathogenic process of ESCC and may be used to
      predict the prognosis of patients with ESCC. 

PMID- 23880165
TI  - Autophagy-related proteins LC3 and Beclin-1 impact the efficacy of chemoradiation
      on esophageal squamous cell carcinoma.
AB  - Autophagy is a bulk protein and organelle degradation process essential for
      cellular maintenance, cell viability and development. This study investigated the
      prognostic role of LC3 and Beclin-1, two autophagy-related proteins, in patients
      with locally advanced esophageal squamous cell carcinoma (ESCC) treated with
      definitive chemoradiation. The data of 150 patients with stages II-IVa ESCC who
      had undergone definitive concurrent chemoradiation were studied; LC3 and Beclin-1
      protein expression was evaluated by immunohistochemistry and western blot. The
      correlations between LC3 and Beclin-1 expression, the patients'
      clinicopathological features, and overall survival were analyzed. Eighty-three
      patients showed positive LC3 and 84 showed positive Beclin-1 protein expressions,
      but LC3 and Beclin-1 expression in ESCC was not significantly correlated
      (P=0.746). LC3 and Beclin-1 expression did not show any association with gender,
      age, tumor location, and treatment response. The median survival of patients with
      positive LC3 expression was 23.6 months, while the median survival was 32.0
      months in patients with negative LC3 expression (P=0.049). The patients with LC3
      and Beclin-1-positive tumors presented much poorer long-term survival.
      Multivariate analysis showed that clinical stage (P=0.019), treatment response
      (P=0.002), and LC3 expression level (P=0.021) were independent predictive factors
      of overall survival in patients with locally advanced ESCC receiving definitive
      chemoradiation. Patients with LC3 and Beclin-1-negative expression had a better
      overall survival than those with LC3 and Beclin-1-positive tumors. LC3 expression
      is an independent prognostic factor for overall survival in ESCC patients treated
      with definitive chemoradiation. 

PMID- 23880166
TI  - Epidermal growth factor receptor abnormalities in atypical teratoid/rhabdoid
      tumors and an unusual case with gene amplification.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is a rhabdoid tumor of the central
      nervous system comprising a mixture of small round cells and mesenchymal and/or
      epithelial elements, showing mutation of the SMARCB1 gene or SMARCA4 gene. The
      epidermal growth factor receptor (EGFR) is one of the tyrosine kinase receptors
      whose overexpressed protein plays important roles in the malignant
      characteristics of various tumors. We analyzed 8 Japanese cases of AT/RT for EGFR
      protein overexpression and egfr gene amplification using immunohistochemistry and
      fluorescence in situ hybridization. The patients included 7 boys and 1 girl (age
      range 13 days to 2 years), and the tumors were localized in the frontal lobe (1
      case), lateral ventricle (1 case), third ventricle (1 case), fourth ventricle (3
      cases), and cerebellum (2 cases). We found that all (100%) of them partially
      expressed a high level of EGFR protein, and that one case showed amplification of
      egfr, the amplified area being localized and limited to a specific area within
      the tumor. We speculate that AT/RT is a tumor with heterogeneous egfr
      amplification, and that the frequency of amplification may depend on loss of
      function of the specific chromatin-remodeling member. 

PMID- 23880167
TI  - Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii
      from a multicentre study in China: molecular epidemiology and resistance
      mechanisms.
AB  - Genetic characterisation of linezolid-resistant Gram-positive cocci in a
      multicentre study in China has not been reported previously. To study the
      mechanism underlying the resistance of linezolid-resistant isolates, nine
      Enterococcus faecalis, one Enterococcus faecium and three Staphylococcus cohnii
      isolates with various levels of resistance were collected from five hospitals
      across China in 2009-2012. The nine E. faecalis isolates were classified into
      seven sequence types, indicating that these linezolid-resistant E. faecalis
      isolates were polyclonal. Enterococci isolates had reduced susceptibility to
      linezolid (MICs of 4-8 mg/L) and had mutation of ribosomal protein L3, with three
      also having mutation of L4, but without the multidrug resistance gene cfr or the
      23S rRNA mutation G2576T. The three S. cohnii isolates were highly resistant to
      linezolid (MICs of 64 mg/L to >256 mg/L), harboured the cfr gene and had the 23S
      rRNA mutation G2576T. Southern blotting indicated that the cfr gene of these
      three isolates resided on different plasmids (pHK01, pRM01 and pRA01). In plasmid
      pHK01, IS21-558 and the cfr gene were integrated into transposon Tn558. In
      plasmids pRM01 and pRA01, the cfr gene was flanked by two copies of an IS256-like
      insertion sequence, indicating that the transferable form of linezolid resistance
      is conferred by the cfr gene. In conclusion, the emergence of linezolid-resistant
      Gram-positive cocci in different regions of China is of concern. The cfr gene and
      the 23S rRNA mutation contribute to high-level linezolid resistance in S. cohnii,
      and the L3 and L4 mutations are associated with low-level linezolid resistance in
      enterococci.

PMID- 23880168
TI  - Activity of dalbavancin, alone and in combination with rifampicin, against
      meticillin-resistant Staphylococcus aureus in a foreign-body infection model.
AB  - The activity of dalbavancin, a representative of the lipoglycopeptide
      antibiotics, alone and in combination with rifampicin, was investigated against
      meticillin-resistant Staphylococcus aureus (MRSA) in a foreign-body infection
      model in guinea pigs. The MIC, MBC and time-kill profile of dalbavancin were
      determined for MRSA ATCC 43300 in the logarithmic (MBC(log)) and stationary
      (MBC(stat)) growth phases. The pharmacokinetic profile of dalbavancin was
      determined in sterile cage fluid in guinea pigs. The activity of intraperitoneal
      dalbavancin (40, 60 or 80 mg/kg as a single dose), rifampicin (12.5 mg/kg/12 h
      for 4 days) and their combination was assessed against planktonic and biofilm
      MRSA. The MIC of dalbavancin was 0.078 mg/L; MBC(log) and MBC(stat) were both
      >128* MIC. In time-kill studies, bacterial reduction of 3log(10)CFU/mL was
      achieved after 48 h at >=32* MIC (logarithmic growth) and at >=1* MIC (stationary
      growth). Dalbavancin was neither synergistic nor antagonistic with rifampicin,
      and prevented the emergence of rifampicin resistance in vitro. The half-life of
      dalbavancin in cage fluid was 35.8-45.4 h and the concentration remained above
      the MIC of MRSA during 7 days after a single dose. Dalbavancin reduced planktonic
      MRSA in cage fluid at high dose (60 mg/kg and 80 mg/kg) but failed to eradicate
      biofilm MRSA from cages. In combination with rifampicin, dalbavancin at 80 mg/kg
      cured 36% of infected cages, and emergence of rifampicin resistance was
      completely prevented. Dalbavancin at 80 mg/kg and in combination with rifampicin
      eradicated approximately one-third of cage-associated MRSA infections and
      prevented emergence of rifampicin resistance.

PMID- 23880169
TI  - ISPa46, a novel insertion sequence in the oprD porin gene of an imipenem
      resistant Pseudomonas aeruginosa isolate from a cystic fibrosis patient in
      Marseille, France.
AB  - Clinical isolates of Pseudomonas aeruginosa exhibiting high-level resistance to
      carbapenems were recovered from a French patient with cystic fibrosis (CF) who
      had not received carbapenem therapy. This study was conducted to investigate the
      molecular mechanism conferring the carbapenem-resistant phenotype in clinical
      isolates of P. aeruginosa recovered from the same CF patient chronically
      colonised since 2005. Investigation of imipenem resistance of P. aeruginosa
      strain_02 isolated in May 2011 showed no carbapenemase activity. However,
      amplification and sequencing of the oprD porin gene revealed disruption of this
      gene by an insertion sequence (IS) element of 1337 bp that contained a novel
      transposase of 1227 bp (ISPa46) bordered by two terminal imperfect inverted
      repeats of 28 bp, which was associated with carbapenem resistance. Retrospective
      analysis of five additional strains of P. aeruginosa isolated before May 2011
      from the same patient revealed that all isolates were likely to be the same clone
      by multilocus sequence typing analysis (ST540/551), but one of the five isolates
      was imipenem-susceptible. Although it was possible to demonstrate the presence of
      ISPa46 in all strains by PCR, this IS was transposed in the oprD gene only for
      imipenem-resistant isolates. Therefore, this study reports a novel IS element
      (ISPa46) in P. aeruginosa clinical isolates of a CF patient in Marseille, France,
      that was associated with carbapenem resistance and was selected in the absence of
      carbapenem treatment.

PMID- 23880170
TI  - What is the relevance of fosfomycin pharmacokinetics in the treatment of serious
      infections in critically ill patients? A systematic review.
AB  - As treatment options for critically ill patients with multidrug-resistant
      bacteria diminish, older antibiotics such as fosfomycin are being investigated
      for use as last-resort drugs. Fosfomycin is a broad-spectrum antibiotic with
      activity both against Gram-positive and Gram-negative bacteria. The aim of this
      review was to examine the effectiveness of current fosfomycin dosing strategies
      in critically ill patients. These patients can be subject to pathophysiology that
      can impact antibiotic pharmacokinetic (PK) profiles and potentially the
      effectiveness of their treatment. As a hydrophilic drug with negligible protein
      binding, fosfomycin is eliminated almost entirely by glomerular filtration and is
      subject to patient renal function. If altered as seen in augmented renal
      clearance, renal function in a critically ill patient may lead to low blood
      concentrations and predispose patients to the risk of treatment failure. If
      altered as seen in acute kidney injury, toxic blood concentrations may develop.
      Fosfomycin has a volume of distribution comparable with beta-lactams and
      aminoglycosides and may therefore increase in critically ill patients. Altered
      dosing strategies may be required to optimise dosing given these PK changes,
      although the current paucity of data on fosfomycin in critically ill patients
      prevents accurate dosing guidance being recommended at this time. 

PMID- 23880171
TI  - Antimicrobial therapy duration: a major matter in the management of severe
      infections.

PMID- 23880172
TI  - Update on the global number of vancomycin-resistant Staphylococcus aureus (VRSA)
      strains.

PMID- 23880173
TI  - Modulation of hepatic redox status and mitochondrial metabolism by exercise:
      therapeutic strategy for liver diseases.
AB  - Liver steatosis (non-alcoholic fatty liver disease, NAFLD) is deemed as the
      hepatic face of the metabolic syndrome, with both physical inactivity and
      hypercaloric/unbalanced diet, together with increasing age playing a role as
      predisposing factors. Consequently, one of the most effective strategies used to
      counteract this scenario is physical exercise. Given the importance of redox
      signaling in cellular remodeling, in which mitochondria are closely implicated
      along with important roles on substrate oxidation, here we briefly review the
      effects of both acute and chronic forms of physical exercise on the modulation of
      hepatic redox state, highlighting the relevance of mitochondrial metabolism and
      function in the induction of liver phenotypes that antagonize metabolic
      alterations associated with liver metabolic diseases. 

PMID- 23880174
TI  - Distribution of CCR5-Delta32, CCR5 promoter 59029 A/G, CCR2-64I and SDF1-3'A
      genetic polymorphisms in HIV-1 infected and uninfected patients in the west
      region of Cameroon.
AB  - BACKGROUND: Genetic variants of the genes encoding human immunodeficiency virus-1
      (HIV-1) co-receptors and their ligands, like CC-chemokine receptor 5 delta 32
      mutation (CCR5-Delta32), CCR5 promoter A/G (Adenine/Guanine), CC-chemokine
      receptor 2 mutation 64 isoleucine (CCR2-64I) and the stromal cell-derived factor
      3'A mutation (SDF1-3'A), are involved in the susceptibility to HIV-1 infection
      and progression. The prevalence of these mutations varies by region. However,
      little is known about their distribution in the population of Dschang, located in
      the west region of Cameroon. The prevalence of HIV in the west region of Cameroon
      is lower than elsewhere in Cameroon. The objectives of this study were to
      determine the distribution of four AIDS Related Gene (ARG) variants in HIV
      infected and non-infected population of Cameroon especially in the west region
      and to estimate the contribution of these variants to the susceptibility or
      resistance to HIV infection. We also aimed to evaluate the effectiveness of
      genotyping using dried blood spot (DBS) samples. METHODS: A total of 179
      participants were recruited from two hospitals in Dschang in the west region of
      Cameroon. Their genotypes for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and
      SDF1-3'A were analyzed using polymerase chain reaction (PCR) and restriction
      fragment length polymorphisms. RESULTS: A total of 179 participants were enrolled
      in the study. Among them, 32 (17.9%) were HIV positive and 147 (82.1%) were HIV
      negative. The allelic frequencies of these genes were: 0%, 49.72%, 17.6% and 100%
      respectively for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3'A. No
      individual was found to carry the CCR5-Delta 32 mutation. All participants
      recruited were heterozygous for the SDF1-3'A allele. CONCLUSION: Our data suggest
      that the CCR5-Delta32 cannot account for the protection as it was completely
      absent in our population. SDF1-3'A variants, may be in association with other
      polymorphisms, may account for the overall protection from HIV-1 infection in
      participants recruited as everyone carries this allele. The CCR5 promoter 59029
      G/G genotype may be associated with the risk for HIV-1 infection in this
      population, while the CCR2-64I (A/A genotype) may account for the protection
      against HIV infection. The results of genotyping from fresh blood and DBS were
      comparable.

PMID- 23880175
TI  - Association between level of exposure to secondhand smoke and peripheral arterial
      disease: cross-sectional study of 5,686 never smokers.
AB  - OBJECTIVE: Active smoking is a recognised risk factor for peripheral arterial
      disease (PAD). Many studies have demonstrated an association between exposure to
      secondhand smoke (SHS) and both coronary heart disease and stroke. In contrast,
      there is a paucity of studies on PAD. The goal of this study was to examine the
      association between level of exposure to SHS and risk of PAD among adults who
      have never smoked. METHODS AND RESULTS: We undertook a cross-sectional study of
      the association between self-reported level of SHS exposure and PAD (defined as
      an ankle brachial pressure index <0.9) using baseline data, from the Scottish
      Family Health Study, on adult (>= 18 years), never smokers. Multivariate logistic
      regression analyses were used to adjust for potential confounders. Of the 5686
      never smokers, 134 (2.4%) had PAD. Three percent of individuals with PAD reported
      being exposed to SHS for >= 40 h per week, compared with only 0.6% of those
      without PAD (chi(2) test, p = 0.010). After adjusting for potential confounders,
      exposure to >= 40 h per week was associated with significantly increased risk of
      PAD (adjusted OR 5.56, 95% CI 1.82-17.06, p = 0.003), with suggestion of a log
      linear dose relationship among those exposed. CONCLUSIONS: In common with
      coronary heart disease and stroke, SHS exposure is an independent risk factor for
      PAD. Our findings lend support to tobacco control efforts aiming at protecting
      the public from SHS exposure.

PMID- 23880176
TI  - Increased carotid intima-media thickness in the physiologic range is associated
      with impaired postprandial glucose metabolism, insulin resistance and beta cell
      dysfunction.
AB  - BACKGROUND: Carotid Intima-Media Thickness (C-IMT) is a reliable predictor of
      cardiovascular events. We examined if increased C-IMT was associated with defects
      in glucose metabolism in non-diabetic subjects independently of age. METHODS: In
      366 Caucasian non-diabetic subjects of the CARAMERIS study, we measured glucose
      response during a 75 g-Oral Glucose Tolerance Test (OGTT), insulin sensitivity
      index (ISI, by Matsuda Index), Liver Insulin Resistance Index (Liver-IR), insulin
      secretion by DeltaAUC Ins0-120/Glu0-120 (DeltaI/DeltaG) and beta cell function
      (Disposition Index, DI). RESULTS: Subjects were divided in two groups according
      to the median age (AGE1 <= 45 y; AGE2 > 45 y). Only 5 subjects in AGE1 and 32 in
      AGE2 had C-IMT > 0.9 mm. Compared to AGE1, AGE2 had a worse cardio-metabolic
      profile, increased cholesterol, glucose and insulin concentrations, blood
      pressure and C-IMT. Both DeltaI/DeltaG ratio and DI were significantly reduced in
      AGE2. By considering tertiles of C-IMT in each AGE group (G1-G3, where G3
      comprised the highest C-IMT), we found that G3 showed increased OGTT glucose
      profiles and Liver IR, decreased ISI and DI, compared to G1 in each AGE group.
      CONCLUSIONS: Increased C-IMT, but within normal ranges, is associated
      independently of age with altered postprandial glucose profile, increased
      peripheral and hepatic insulin resistance, decreased b-cell function. C-IMT
      measurement should become a routine analysis even in younger subjects to predict
      the risk of cardio-metabolic disease.

PMID- 23880177
TI  - Local and systemic effects of leg cycling training on arterial wall thickness in
      healthy humans.
AB  - Exercise training is associated with direct effects on conduit artery function
      and structure. Cross-sectional studies suggest the presence of systemic changes
      in wall thickness as a result of exercise in healthy subjects, but no previous
      study has examined this question in humans undertaking exercise training.
      OBJECTIVE: To examine the change in superficial femoral (SFA, i.e. local effect)
      and carotid (CA, i.e. systemic effect) artery wall thickness across 8 weeks of
      lower limb cycle training in healthy young men. METHODS: Fourteen healthy young
      male subjects were assigned to an 8-week training study of cycling exercise (n =
      9) or a control period (n = 5). Before, during (2, 4 and 6 weeks) and after
      training, SFA and CA wall thickness was examined using automated edge-detection
      of high resolution ultrasound images. We also measured resting diameter and
      calculated the wall:lumen(W:L)-ratio. RESULTS: Exercise training did not alter CA
      or SFA baseline diameter (P = 0.14), but was associated with gradual, consistent
      and significant decreases in wall thickness and W:L-ratio in both the CA and SFA
      (P < 0.001 and 0.002, respectively). Two-way ANOVA revealed a comparable
      magnitude of decrease in wall thickness and W:L-ratio in both arteries across the
      8-week period (interaction-effect; P = 0.29 and 0.12, respectively). No changes
      in artery diameter, wall thickness or W:L-ratio were apparent in controls (0.82,
      0.38 and 0.52, respectively). CONCLUSION: We found that cycle exercise training
      in healthy young individuals is associated with modest, but significant,
      decreases in wall thickness in the superficial femoral and carotid arteries.
      These findings suggest that exercise training causes systemic adaptation of the
      arterial wall in healthy young subjects.

PMID- 23880178
TI  - Activation of receptor for advanced glycation end products contributes to aortic
      remodeling and endothelial dysfunction in sinoaortic denervated rats.
AB  - OBJECTIVE: The aim of present study was to test the hypothesis that activation of
      receptor for advanced glycation end products (RAGE) pathway contributes to aortic
      remodeling and endothelial dysfunction in sinoaortic denervated (SAD) rats.
      METHODS AND RESULTS: Experiment 1: 8 weeks after sinoaortic denervation, aortas
      were removed for measurement of AGE/RAGE pathway. Sinoaortic denervation in rats
      resulted in enhanced activity of aldose reductase, reduced activity of glyoxalase
      1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE in
      aortas. Experiment 2: 5 weeks after sinoaortic denervation, the rats received
      intraperitoneal injections of 500 MUg soluble RAGE (sRAGE) daily for 3 weeks.
      Treatment of SAD rats with sRAGE attenuated aortic remodeling, marked by
      reduction in AW/length, wall thickness, proliferation of SMC, and collagen
      deposition, and improvement of endothelial function. Treatment of SAD rats with
      sRAGE abated aortic oxidative stress, marked by reduction in formation of
      malondialdehyde, reactive oxygen species, superoxide, peroxynitrite and 3
      nitrotyrosine, and enhancement of ratio of GSH/GSSG. Treatment of SAD rats with
      sRAGE attenuated aortic mitochondrial dysfunction. Treatment of SAD rats with
      sRAGE suppressed aortic NFkappaB nuclear translocation and inflammation.
      Treatment of SAD rats with sRAGE restored aortic NO formation through
      upregulating eNOS and dimethylarginine dimethylaminohydrolase-2 and
      downregulating protein arginine methyltransferase-1. CONCLUSION: Activated RAGE
      contributed to aortic remodeling and endothelial dysfunction in SAD rats,
      possibly via induction of oxidative stress and inflammation, impairment of
      mitochondrial function, and reduction in NO bioavailability.

PMID- 23880179
TI  - Fish oil-enriched diet protects against ischemia by improving angiogenesis,
      endothelial progenitor cell function and postnatal neovascularization.
AB  - BACKGROUND: Fish oil consumption has been associated with a reduced incidence of
      cardiovascular diseases. However, the precise mechanisms involved are not
      completely understood. Here we tested the hypothesis that a fish oil-enriched
      diet improves neovascularization in response to ischemia. METHODS AND RESULTS:
      C57Bl/6 mice were fed a diet containing either 20% fish oil, rich in long-chain n
      3 polyunsaturated fatty acids (PUFAs), or 20% corn oil, rich in n-6 PUFAs. After
      4 weeks, hindlimb ischemia was surgically induced by femoral artery removal. We
      found that blood flow recovery was significantly improved in mice fed a fish oil
      diet compared to those fed a corn oil diet (Doppler flow ratio (DFR) at day 21
      after surgery 78 +/- 5 vs. 56 +/- 4; p < 0.01). Clinically, this was associated
      with a significant reduction of ambulatory impairment and ischemic damage in the
      fish oil group. At the microvascular level, capillary density was significantly
      improved in ischemic muscles of mice fed a fish oil diet. This correlated with
      increased expression of VEGF and eNOS in ischemic muscles, and higher NO
      concentration in the plasma. Endothelial progenitor cells (EPCs) have been shown
      to have an important role for postnatal neovascularization. We found that the
      number of EPCs was significantly increased in mice fed a fish oil diet. In
      addition, oxidative stress levels (DCF-DA, DHE) were reduced in EPCs isolated
      from mice exposed to fish oil, and this was associated with improved EPC
      functional activities (migration and integration into tubules). In vitro,
      treatment of EPCs with fish oil resulted in a significant increase of cellular
      migration. In addition, the secretion of angiogenic growth factors including IL6
      and leptin was significantly increased in EPCs exposed to fish oil. CONCLUSION:
      Fish oil-enriched diet is associated with improved neovascularization in response
      to ischemia. Potential mechanisms involved include activation of VEGF/NO pathway
      in ischemic tissues together with an increase in the number and the functional
      activities of EPCs.

PMID- 23880180
TI  - Pharmaceutical stabilization of mast cells attenuates experimental atherogenesis
      in low-density lipoprotein receptor-deficient mice.
AB  - Mast cells (MCs) contribute to atherogenesis by releasing pro-inflammatory
      mediators to activate vascular cells and other inflammatory cells. This study
      examined whether MC activation or stabilization affects diet-induced
      atherosclerosis in low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice.
      When Ldlr(-/-) mice consumed an atherogenic diet for 3 or 6 months, MC activation
      with compound 48/80 (C48/80) increased aortic arch intima and total lesion areas,
      and plasma total cholesterol, LDL, and triglyceride levels, whereas MC
      stabilization with cromolyn reduced these parameters. There were significant
      differences in arch intima and total lesion areas, and plasma total cholesterol,
      LDL, and triglyceride levels between C48/80-treated and cromolyn-treated mice. To
      examine a therapeutic application of cromolyn in atherosclerosis, we fed Ldlr(-/
      ) mice an atherogenic diet for 3 months followed by giving mice cromolyn for
      additional 3 months. Cromolyn did not affect aortic arch intima area, but
      significantly reduced lipid deposition in the thoracic-abdominal aortas. In
      aortic arches, however, cromolyn treatment significantly reduced lesion contents
      of Mac-3(+) macrophages, CD4(+) T cells, activated MCs, and lesion cell
      proliferation. While plasma total cholesterol and LDL levels increased and high
      density lipoprotein (HDL) levels decreased from 3 months to 6 months of an
      atherogenic diet, cromolyn treatment decreased significantly plasma total
      cholesterol, LDL, and triglyceride levels and increased HDL levels above those of
      3-month time point. These observations demonstrate that MC stabilization reduces
      lesion inflammation, ameliorates plasma lipid profiles, and may serve as a
      potential therapy for this cardiovascular disease.

PMID- 23880182
TI  - Low ankle-brachial index and risk of stroke.
AB  - OBJECTIVE: Many studies have evaluated the association between a low ankle
      brachial index (ABI) and the risk of stroke events; however, their results are
      inconsistent. The aim of the present study was to determine the association
      between a low ABI (ABI < 0.9) and the risk of stroke events by conducting a meta
      analysis. METHODS: Electronic literature databases (Medline, and Embase) were
      searched for relevant prospective observational studies published prior to
      December 2012. Only prospective studies that detected stroke events for
      participants with low ABI in general population during the follow-up period were
      selected. The results were presented as relative risk (RR) and the 95% confidence
      interval (CI) comparing low ABI (ABI < 0.9) to the ABI (>=0.9) category. RESULTS:
      After the initial search, we identified 10 studies with a total of 22,355
      participants that met our inclusion criteria. Overall, low ABI was associated
      with an increased risk of subsequent stroke (RR 1.43; 95% CI 1.23-1.65), and
      ischemic stroke (RR 1.83; 95% CI 1.29-2.58). In addition, a low ABI was also
      associated with an increased risk of recurrent strokes (RR 3.02; 95% CI 1.26
      7.25). However, a low ABI was not associated with an increased risk of
      hemorrhagic stroke (RR 1.55; 95% CI 0.34-7.08). CONCLUSIONS: Our results suggest
      that a low ABI appears to be an independent predictor for ischemic and recurrent
      stroke events. The low ABI provides supplemental information on subjects who are
      at increased risk of subsequent stroke events.

PMID- 23880181
TI  - Associations between aspirin and other non-steroidal anti-inflammatory drugs and
      aortic valve or coronary artery calcification: the Multi-Ethnic Study of
      Atherosclerosis and the Heinz Nixdorf Recall Study.
AB  - BACKGROUND: The association between non-steroidal anti-inflammatory drugs
      (NSAIDs) and the incidence of valvular and arterial calcification is not well
      established despite known associations between these drugs and cardiovascular
      events. OBJECTIVE: To compare the association between the baseline use of aspirin
      with other NSAID class medications with the incidence and prevalence of aortic
      valve calcification (AVC) and coronary artery calcification (CAC). METHODS: The
      relationship of NSAID use to AVC and CAC detected by computed tomography was
      assessed in 6814 participants within the Multi-Ethnic Study of Atherosclerosis
      (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity,
      study site, anti-hypertensive medication use, education, income, health insurance
      status, diabetes, smoking, exercise, body mass index, blood pressure, serum
      lipids, inflammatory markers, fasting glucose, statin medication use, and a
      simple diet score. Medication use was assessed by medication inventory at
      baseline which includes the use of non-prescription NSAIDs. MESA collects
      information on both incident and prevalent calcification. The 4814 participants
      of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with
      similar measures of calcification, were included in this analysis to enable
      replication. RESULTS: Mean age of the MESA participants was 62 years (51%
      female). After adjustment for possible confounding factors, a possible
      association between aspirin use and incident AVC (Relative Risk(RR): 1.60;
      95%Confidence Interval (CI): 1.19-2.15) did not replicate in the HNR cohort (RR:
      1.06; 95%CI: 0.87-1.28). There was no significant association between aspirin use
      and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91-1.29) or in the HNR
      cohort (RR 1.24; 95%CI: 0.87-1.77). Non-aspirin NSAID use was not associated with
      either AVC or CAC in either cohort. There were no associations between regular
      cardiac dose aspirin and incident calcification in either cohort. CONCLUSION:
      Baseline NSAID use, as assessed by medication inventory, appears to have no
      protective effect regarding the onset of calcification in either coronary
      arteries or aortic valves.

PMID- 23880183
TI  - A novel noninvasive and simple method for assessment of endothelial function:
      enclosed zone flow-mediated vasodilation (ezFMD) using an oscillation amplitude
      measurement.
AB  - BACKGROUND: It is clinically important to estimate the degree of endothelial
      dysfunction. Several methods have been used to assess endothelial function in
      humans. Recently, we developed a new noninvasive method for measurement of
      vascular response to reactive hyperemia in the brachial artery, named enclosed
      zone flow-mediated vasodilation (ezFMD). The purpose of this study was to
      determine the validity of ezFMD for assessment of endothelial function. METHODS
      AND RESULTS: We measured ezFMD by a new device using an oscillometric method and
      conventional FMD using ultrasonography in 306 subjects, including patients with
      hypertension, dyslipidemia, and diabetes mellitus (218 men and 88 women, 30 +/-
      16 yr). Univariate regression analysis revealed that ezFMD significantly
      correlated with age (r = -0.42, P < 0.0001), body mass index (r = -0.13, P =
      0.028), systolic blood pressure (r = -0.15, P = 0.009), diastolic blood pressure
      (r = -0.14, P = 0.011), fasting glucose level (r = -0.27, P = 0.006), smoking (r
      = -0.21, P = 0.007) and baseline pulse wave amplitude (r = -0.51, P < 0.0001).
      ezFMD significantly correlated with conventional FMD (r = 0.34, P < 0.0001).
      Multiple regression analysis revealed that age (P = 0.002), body mass index (P =
      0.013), systolic blood pressure (P = 0.009), smoking (P = 0.004) and baseline
      pulse wave amplitude (P < 0.001) were independent predictors of ezFMD.
      CONCLUSIONS: These findings suggest that measurement of ezFMD, a novel
      noninvasive and simple method, may be useful for determination of vascular
      diameter response to reactive hyperemia. Since ezFMD is automatically measured by
      a device with an oscillometric method, measurement of ezFMD is easier and less
      biased than that of conventional FMD.

PMID- 23880184
TI  - Role of the angiotensin converting enzyme 1/angiotensin II/angiotensin receptor 1
      axis in interstitial collagenase expression in human carotid atheroma.
AB  - BACKGROUND AND AIM: Angiotensin II (AII) receptor 1 (ATR1) and angiotensin
      converting enzyme 1 (ACE1) blockers have been shown to reduce acute
      cardiovascular events in patients, improve plaque stability and modify matrix
      metalloproteinase (MMP) expression. However, the role of the ACE1/AII/ATR1 axis
      in interstitial collagenase regulation has not been fully explored. In this
      study, we investigated the effect of ATR1 and ACE1 blockade on the expression and
      activity of MMP-1, -8 and -13 in human carotid atheroma. METHODS: Atheroma
      samples (n = 24) were obtained from patients undergoing carotid endarterectomy.
      The effects of ATR1 (irbesartan), ACE1 (quinapril), ACE2 (DX600) and MMP (GM6001)
      blockade on the expression of AII, the interstitial collagenases and soluble
      elastin fragments were investigated in explant culture supernatants. Paired
      atheroma samples were incubated with intervention or media control for 4 days.
      Protein levels (AII, MMP-1, -8, -13 and soluble elastin) were determined by
      ELISA. RESULTS: ATR1, but not ACE1, blockade significantly reduced MMP-1 and -8
      concentrations in atheroma supernatants. ACE2 blockade significantly increased
      MMP-1 and -8 concentrations in atheroma supernatants. AII concentration in
      atheroma supernatants significantly increased after ATR1, ACE1 and ACE2 blockade.
      Release of soluble elastin fragments increased after ATR1 and ACE1 blockade, but
      was not changed by an MMP inhibitor. CONCLUSIONS: Our findings suggest that ATR1
      blockade alters AII, MMP-1, MMP-8 expression and a marker of elastin degradation
      in human atheroma, but that the elastin degradation response is not MMP driven.
      This data contributes to the recognised ability of ATR1 blockade to modify plaque
      stability.

PMID- 23880185
TI  - Flow cytometry and gene expression profiling of immune cells of the carotid
      plaque and peripheral blood.
AB  - OBJECTIVES: The relative contribution of the local vs. peripheral inflammation to
      the atherothrombotic processes is unknown. We compared the inflammatory status of
      the immune cells of the carotid plaque with similar cells in peripheral
      circulation of patients with advanced carotid disease (PCDs). METHODS:
      Mononuclear cells (MNCs) were extracted from carotid endarterectomy (CEA) samples
      by enzymatic digestion and subsequent magnetic cell sorting. The cell surface
      antigenic expressions, and mRNA expression levels were compared between CEA MNCs
      and peripheral MNCs, using flow cytometry and RT-PCR techniques. RESULTS: The
      percentages of resting MNCs were lower, and activated MNCs, particularly
      monocytes, were higher in the CEAMNCs, as compared to the peripheral MNCs. The
      percentages of activated T cells and B cells were higher in the peripheral MNCs
      of PCDs, than in healthy controls (HCs), but the percentages of activated
      monocytes did not differ between the two groups. The expression levels of both
      pro-inflammatory/pro-thrombotic (P(38), JNKB-1, Egr-1 PAI-1, MCP-1, TF, MMP-9,
      HMGB-1, TNF-alpha, mTOR) and anti-inflammatory (PPAR-gamma, TGF-beta) mediators
      were significantly higher in the CEA MNCs as compared to the peripheral MNCs.
      Furthermore, MMP-9 and PPAR-gamma expression levels were higher in the peripheral
      MNCs of PCDs than HCs. CONCLUSION: The inflammatory status is higher in the
      immune cells of the carotid plaque, as compared to those cells in the peripheral
      blood. The altered expression levels of both pro-inflammatory/pro-thrombotic and
      anti-inflammatory mediators in the milieu of the plaque suggest that the balance
      between these various mediators may play a key role in carotid disease
      progression.

PMID- 23880186
TI  - The microRNA miR-132 targets Lrrfip1 to block vascular smooth muscle cell
      proliferation and neointimal hyperplasia.
AB  - OBJECTIVE: The proliferation and remodeling of vascular smooth muscle cells
      (VSMCs) is an important pathological event in atherosclerosis and restenosis.
      Here we report that microRNA-132 (miR-132) blocks vascular smooth muscle cells
      (VSMC) proliferation by inhibiting the expression of LRRFIP1 [leucine-rich repeat
      (in Flightless 1) interacting protein-1]. METHODS AND RESULTS: MicroRNA
      microarray revealed that miR-132 was upregulated in the rat carotid artery after
      catheter injury, which was further confirmed by quantitative real-time RT-PCR.
      Transfection of a miR-132 mimic significantly inhibited the proliferation of
      VSMCs, whereas transfection of a miR-132 antagomir increased it. miR-132 mimic
      inhibited VSMC migration and induced apoptosis. miR-132 mimic increased the
      protein amounts of both p27 and smooth muscle (SM) alpha-actin, whereas it
      decreased SM alpha-actin and Bcl2. Bioinformatics showed that LRRFIP1 is a target
      candidate of miR-132. miR-132 down-regulated luciferase activity driven by a
      vector containing the 3'-untranslated region of Lrrfip1 in a sequence-specific
      manner. LRRFIP1 induced VSMC proliferation and increased phosphorylation of ERK.
      Immunohistochemical analysis revealed that Lrrfip1 was clearly expressed along
      with the basal laminar area of smooth muscle, and its expression pattern was
      disrupted 7 days after arterial injury. LRRFIP1 mRNA was decreased 14 days after
      injury. Delivery of miR-132 to rat carotid artery reduced LRRFIP1 expression and
      attenuated neointimal proliferation in carotid artery injury models. CONCLUSIONS:
      Our results suggest that miR-132 is a novel regulator of VSMC proliferation that
      represses neointimal formation by inhibiting LRRFIP1 expression.

PMID- 23880187
TI  - CD14 and TLR4 mediate cytokine release promoted by electronegative LDL in
      monocytes.
AB  - AIMS: Electronegative LDL (LDL(-)), a minor modified LDL present in the
      circulation, induces cytokine release in monocytes. We aimed to determine the
      role of the receptor CD14 and toll-like receptors 2 and 4 (TLR2, TLR4) in the
      inflammatory action promoted by LDL(-) in human monocytes. METHODS AND RESULTS:
      Monocytes were preincubated with antibodies to neutralize CD14, TLR2 and TLR4.
      The release of monocyte chemoattractant protein 1 (MCP1), and interleukin 6 and
      10 (IL6 and IL10) promoted by LDL(-) was inhibited 70-80% by antiCD14 and
      antiTLR4, and 15-25% by antiTLR2. The involvement of CD14 and TLR4 was confirmed
      by gene silencing experiments. The human monocytic THP1 cell line overexpressing
      CD14 released more cytokines in response to LDL(-) than the same THP1 cell line
      without expressing CD14. VIPER, a specific inhibitor of the TLR4 signaling
      pathway, blocked 75-90% the cytokine release promoted by LDL(-). Cell binding
      experiments showed that monocytes preincubated with neutralizing antibodies
      presented lesser LDL(-) binding than non-preincubated monocytes The inhibitory
      capacity was antiCD14>antiTLR4>>antiTLR2. Cell-free experiments performed in CD14
      coated microtiter wells confirmed that CD14 was involved in LDL(-) binding. When
      LDL(-) and lipopolysaccharide (LPS) were added simultaneously to monocytes,
      cytokine release was similar to that promoted by LDL(-) alone. Binding
      experiments showed that LDL(-) and LPS competed for binding to monocytes and to
      CD14 coated-wells. CONCLUSIONS: CD14 and TLR4 mediate cytokine release induced by
      LDL(-) in human monocytes. The cross-competition between LPS and LDL(-) for the
      same receptors could be a counteracting action of LDL(-) in inflammatory
      situations.

PMID- 23880188
TI  - Leukocyte telomere length and coronary artery calcification in Palestinians.
AB  - OBJECTIVE: Shorter leukocyte telomere length (LTL) is associated with higher
      incidence of coronary heart disease (CHD) and increased mortality. We examined
      the association of LTL with coronary artery calcification (CAC), which reflects
      the cumulative burden of coronary atherosclerosis, in an urban Arab sample of
      Palestinians, a population at high risk of CHD. METHODS: Using a cross-sectional
      design, a random sample of East Jerusalem residents, comprising 250 men aged 45
      77 and women aged 55-76 and free of CHD or past stroke, was drawn from the Israel
      national population register. LTL was measured by Southern blots. CAC was
      determined by 16-slice multidetector helical CT scanning using Agatston scoring.
      We applied multivariable logistic modeling to examine the association between sex
      specific tertiles of LTL and CAC (comparing scores >100 vs. <100, and the upper
      third vs. the lower 2 thirds), controlling for age, sex, education and coronary
      risk factors. RESULTS: CAC, evident in 65% of men and 52% of women, was strongly
      associated with age (sex-adjusted Spearman's rho 0.495). The multivariable
      adjusted odds ratios for CAC >100 (found in 30% of men and 29% of women) were
      2.92 (95% CI 1.28-6.68) and 2.29 (0.99-5.30) for the lower and mid-tertiles of
      LTL vs. the upper tertile, respectively (Ptrend = 0.008). Findings were similar
      for CAC scores in the upper tertile (Ptrend = 0.006), and persisted after the
      exclusion of patients with diabetes or receiving statins. CONCLUSIONS: Shorter
      LTL was associated with a greater prevalence of asymptomatic coronary
      atherosclerosis in an urban Arab population-based sample. Mechanisms underlying
      this association should be sought.

PMID- 23880189
TI  - Association between cardiac valvular calcification and myocardial ischemia in
      asymptomatic high-risk patients with end-stage renal disease.
AB  - OBJECTIVE: Valvular calcification is associated with significant morbidity and
      mortality in patients with end stage renal disease (ESRD). This study examined
      the hypothesis that valvular calcification is a marker of myocardial ischemia in
      asymptomatic high-risk patients with ESRD. METHODS: Echocardiography and
      myocardial perfusion single-photon emission computed tomography were performed in
      285 asymptomatic high-risk patients with ESRD at initiation of dialysis. We
      evaluated the extent and severity of myocardial ischemia by the summed difference
      score (SDS) and defined the presence of myocardial ischemia as SDS >= 3 and
      moderate to severe ischemia as SDS >= 8. The presence of cardiac valvular
      calcification was assessed by echocardiography and defined as aortic valve
      calcification or mitral valve calcification. RESULTS: Eighty-five (29.9%)
      patients had echocardiographic evidence of cardiac valvular calcification. The
      presence of myocardial ischemia was significantly associated with aortic valve
      calcification (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.76-5.78;
      p < 0.001), mitral valve calcification (OR = 3.31; 95% CI = 1.74-6.28; p <
      0.001), and cardiac valvular calcification (OR = 3.18; 95% CI = 1.79-5.65; p <
      0.001). The presence of moderate to severe myocardial ischemia (SDS >= 8) was
      independently associated with cardiac valvular calcification (OR = 2.86; 95% CI =
      1.12-7.27; p = 0.028). CONCLUSION: Valvular calcification was significantly
      associated with the presence of inducible myocardial ischemia in asymptomatic
      patients with ESRD, and may be a potential marker of patients at high-risk for
      the presence of silent myocardial ischemia.

PMID- 23880191
TI  - Egg consumption and coronary atherosclerotic burden.
AB  - OBJECTIVE: To verify the association between egg consumption and coronary
      atherosclerotic burden. DESIGN: Observational study. SETTING: Cardiac
      catheterization laboratory. PARTICIPANTS: Adult patients referred for coronary
      angiography. MEASUREMENTS: Socio-demographic data (age, education level, and
      occupation), cardiovascular risk factors (smoking, systemic hypertension,
      dyslipidemia, diabetes, and family history of coronary artery disease), and egg
      eating habits were assessed using a research questionnaire. Egg consumption was
      divided into three categories: less than one egg a week; one egg a week; and more
      than one egg a week. Coronary atherosclerotic burden was assessed by a blinded
      interventional cardiologist using the Friesinger Score (FS) obtained from the
      coronary angiography. This score varies from 0 to 15 and evaluated each of the
      three main coronary arteries separately. For this analysis, the FS was divided
      into three categories: 0-4, 5-9, and 10-15. RESULTS: The study sample was
      composed of 382 adult patients; 241 patients (63.3%) were male. The average age
      was 60.3 +/- 10.8 years (range 23-89 years). The egg-eating category was
      inversely associated with dyslipidemia (p < 0.05) but not with the other
      cardiovascular risk factors. A significant association was found between egg
      consumption and FS (p < 0.05), showing that patients who ate more than one egg a
      week had a lower coronary atherosclerotic burden. By multivariate analysis, the
      atherosclerotic burden was independently associated with sex, age, hypertension
      and egg consumption. CONCLUSION: In this observational study of patients
      undergoing coronary angiography, the consumption of more than one egg per week
      was associated with a lower coronary atherosclerotic burden.

PMID- 23880190
TI  - Inhibition of ileal apical but not basolateral bile acid transport reduces
      atherosclerosis in apoE-/- mice.
AB  - OBJECTIVE: Interruption of the enterohepatic circulation of bile acids induces
      hepatic bile acid synthesis, increases hepatic cholesterol demand, and increases
      clearance of apoB-containing lipoproteins in plasma. Based on these effects, bile
      acid sequestrants have been used for many years to treat hypercholesterolemia and
      the associated atherosclerosis. The objective of this study was to determine the
      effect of blocking ileal apical versus basolateral membrane bile acid transport
      on the development of hypercholesterolemia and atherosclerosis in mouse models.
      METHODS AND RESULTS: ApoE(-/-) and Ldlr(-/-) mice deficient in the apical sodium
      dependent bile acid transporter (Asbt) or apoE(-/-) mice deficient in the
      basolateral bile acid transporter (Ostalpha) were fed an atherogenic diet for 16
      weeks. Bile acid metabolism, cholesterol metabolism, gene expression, and
      development of atherosclerosis were examined. Mice deficient in Asbt exhibited
      the classic response to interruption of the enterohepatic circulation of bile
      acids, including significant reductions in hepatic and plasma cholesterol levels,
      and reduced aortic cholesteryl ester content. Ileal Fibroblast Growth Factor-15
      (FGF15) expression was significantly reduced in Asbt(-/-)apoE(-/-) mice and was
      inversely correlated with expression of hepatic cholesterol 7-hydroxylase
      (Cyp7a1). Ileal FGF15 expression was directly correlated with plasma cholesterol
      levels and aortic cholesterol content. In contrast, plasma and hepatic
      cholesterol levels and atherosclerosis development were not reduced in apoE(-/-)
      mice deficient in Ostalpha. CONCLUSIONS: Decreases in ileal FGF15, with
      subsequent increases in hepatic Cyp7a1 expression and bile acid synthesis appear
      to be necessary for the plasma cholesterol-lowering and atheroprotective effects
      associated with blocking intestinal bile acid absorption.

PMID- 23880192
TI  - Metformin impairs endothelialization after placement of newer generation drug
      eluting stents.
AB  - OBJECTIVES: Metformin impairs endothelialization of drug eluting stents (DES) due
      to convergent signaling at the mammalian target of rapamycin (mTOR) pathway. We
      assessed whether metformin will continue to adversely affect stent
      endothelialization despite design improvements in newer generation DES. METHODS:
      Rabbit iliac artery stenting with newer generation DES was performed followed by
      14 days of either normal chow diet or one with metformin (100 mg/kg/day) added.
      Scanning electron microscopy was used to assess stent endothelialization after
      sacrifice. RESULTS: In the metformin-treated group there was significantly less
      endothelialization compared to the placebo-treated group. Paclitaxel-eluting
      stents in placebo-treated group had the greatest degree of endothelialization
      with significantly less in its metformin-treated counterpart and all-limus
      eluting stent groups. CONCLUSIONS: Metformin inhibited stent endothelialization
      in newer generation DES despite improvements in stent design. By impairing stent
      endothelialization, metformin may increase the risk for thrombotic complications
      after newer generation DES placement.

PMID- 23880193
TI  - Association of body mass index with arterial stiffness and blood pressure
      components: a twin study.
AB  - RATIONALE: Obesity, blood pressure and arterial stiffness are heritable traits
      interconnected to each other but their possible common genetic and environmental
      etiologies are unknown. METHODS: We studied 228 monozygotic and 150 dizygotic
      twin pairs aged 18-82 years from Italy, Hungary and the United States, of which
      45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI;
      intrapair difference (Delta) in BMI >= 3 kg/m(2)). Blood pressure components and
      arterial stiffness were measured by TensioMed Arteriograph. RESULTS: Hypertension
      was more prevalent among obese than non-obese individuals (55% vs. 29%, p <
      0.001). Age-, sex- and country-adjusted heritability estimates were high for
      hemodynamic measures (45%-58%) and BMI (78%). According to bivariate Cholesky
      decomposition, phenotypic correlations between BMI and blood pressure components
      (r = -0.15 to 0.24, p < 0.05) were largely explained by additive genetic factors
      (65%-77%) with the remaining explained by the unique environment. When
      controlling for genetic factors within all monozygotic pairs, DeltaBMI was
      significantly correlated with Deltabrachial systolic blood pressure (SBP) and
      diastolic blood pressure (DBP), Deltamean arterial pressure, and Deltaaortic SBP
      (r = 0.15-0.17, p < 0.05). For the same measures, heavier co-twins of BMI
      discordant monozygotic pairs had significantly higher values than their leaner
      counterparts (p < 0.05). CONCLUSION: Blood pressure components are moderately
      correlated with BMI, largely because of shared genetic factors. However, for the
      association of BMI with brachial SBP and DBP, aortic SBP and mean arterial
      pressure, acquired, modifiable factors were also found to be important.

PMID- 23880194
TI  - Critical limb ischaemia is characterised by an increased production of whole
      blood reactive oxygen species and expression of TREM-1 on neutrophils.
AB  - BACKGROUND: Atherosclerosis is a chronic inflammatory process involving
      polymorphonuclear neutrophils (PMN) and formation of reactive oxygen species
      (ROS). The aim of the present study was to investigate the phenotype of
      inflammatory cells in regard to the expression of triggering receptor expressed
      on myeloid cells (TREM)-1 and its soluble form (sTREM-1) as well as its
      relationship with oxidative stress in peripheral artery disease (PAD) patients.
      METHODS: In total 90 patients with PAD (N = 30 intermittent claudication (IC) >
      300 m absolute walking distance, N = 30 IC < 300 m absolute walking distance, N =
      30 critical limb ischaemia (CLI)) and 30 control persons were included. ROS
      formation was measured at basal or stimulated conditions using the luminol
      analogue L-012 chemiluminescence. Peripheral blood leucocytes were analysed from
      whole blood by flow cytometry using different gating strategies to identify PMN
      and monocytes and analyse TREM-1 expression. RESULTS: CLI patients showed a
      significant higher ROS production at basal levels (p < 0.05) and upon stimulation
      with PDBu (p < 0.0001), LPS (p < 0.05) and zymosan A (p < 0.0001). TREM-1 was
      expressed significantly more on PMN of CLI patients (p < 0.01) in comparison to
      all other groups, whereas monocytic expression of TREM-1 was similar between all
      4 groups. The serum concentration of its soluble form sTREM-1 however was
      increased in CLI and IC < 300 m patients (p < 0.0001). sTREM-1 concentrations
      correlated with basal ROS levels as wells with ROS production upon stimulation.
      Furthermore, we found the walking distance of IC patients to inversely correlate
      with sTREM-1 (rs = - 0.29; p = 0.03). CONCLUSIONS: We found an increased
      oxidative stress as well as an increased expression of TREM-1 and serum levels of
      sTREM-1 in patients with CLI. IC < 300 m patients showed a similar patter in
      regard to oxidative stress, TREM-1 expression and sTREM-1 concentration. Thus,
      sTREM-1 might represent a potential inflammatory biomarker to evaluate the
      severity of PAD. Whether this implies the potential for therapeutic
      recommendations, i.e. conservative vs. interventional/operative treatment, or a
      possibility to monitor the efficacy of interventions, requires further studies.

PMID- 23880195
TI  - Statin therapy and secretory phospholipase A2 in children with heterozygous
      familial hypercholesterolemia.
AB  - OBJECTIVE: Secretory phospholipase A2 (sPLA2) enzymes are thought to contribute
      to atherosclerosis. In this study we assessed levels of sPLA2 mass and activity,
      and their relationship to baseline characteristics of children with familial
      hypercholesterolemia (FH). Furthermore, we evaluated the effect of two years of
      pravastatin therapy on sPLA2 levels. METHODS AND RESULTS: sPLA2-IIA mass and
      sPLA2 activity were measured at baseline and after two years in 187 children with
      FH (aged 8-18 years) randomized to pravastatin or placebo. At baseline, median
      [IQR] sPLA2-IIA mass and sPLA2 activity levels were 7.2 [5.8-13.2] ng/ml and 36.4
      [29.8-47.1] U/ml, respectively. Both sPLA2-IIA mass and sPLA2 activity were
      significantly correlated with high-sensitivity C-reactive protein (r = 0.33, p <
      0.001 and r = 0.386, p < 0 .001, respectively), but not with other cardiovascular
      risk factors. Baseline levels of sPLA2-IIA mass and sPLA2 activity were not
      significantly associated with carotid intima-media thickness (cIMT) at baseline
      or at the end of follow-up. After two years, sPLA2-IIA mass and sPLA2 activity
      levels were not significantly reduced in the pravastatin group (p = 0.20 and p =
      0.63, respectively), nor in the placebo group (p = 0.17 and p = 0.11,
      respectively). Changes from baseline did not differ between the treatment groups
      for sPLA2-IIA mass (p = 0.48) and sPLA2 activity (p = 0.88). CONCLUSIONS: sPLA2
      IIA mass and sPLA2 activity were not significantly associated with cIMT in our
      pediatric FH cohort. This could indicate that the potential predictive role of
      sPLA2 as a biomarker of cardiovascular disease in children with FH is limited.
      Treatment with pravastatin did not reduce sPLA2-IIA mass or sPLA2 activity
      levels, as compared to placebo. Further studies with larger samples are required
      to address these issues.

PMID- 23880196
TI  - EP 80317, a CD36 selective ligand, promotes reverse cholesterol transport in
      apolipoprotein E-deficient mice.
AB  - AIMS: The CD36 selective ligand, EP 80317, features potent anti-atherosclerotic
      and hypocholesterolemic effects that are associated with an increase in
      macrophage cholesterol efflux through the activation of the peroxisome
      proliferator-activated receptor gamma-liver X receptor alpha (LXRalpha)-ATP
      binding cassette (ABC) transporter pathway. Cholesterol efflux is the first step
      of reverse cholesterol transport (RCT). However, whether EP 80317 exerts its
      hypocholesterolemic and anti-atherosclerotic activity through RCT in vivo has yet
      to be determined. In the present study, we investigated the effects of EP 80317
      on RCT, in particular on macrophage-to-feces RCT and the expression of selected
      genes associated with hepatic cholesterol metabolism and intestinal cholesterol
      transport. METHODS AND RESULTS: Reverse cholesterol transport was assessed
      following the intraperitoneal injection of [(3)H]-cholesterol-labelled J774
      macrophages to hypercholesterolemic apoE- and apoE/CD36 double-deficient mice
      that had been treated for 12 weeks with EP 80317. Forty-eight hours after the
      administration of [(3)H]-cholesterol-labelled cells, blood, liver, intestines and
      feces were harvested. The radioactivity recovered in the feces (cholesterol and
      bile acid combined) was significantly increased by 311% (P = 0.0259) in EP 80317
      treated mice compared with that found in vehicle-treated mice despite no
      significant change in [(3)H]-tracer recovery in plasma between groups. Whereas
      the mRNA levels of LXRalpha in the gut were significantly upregulated, mRNA and
      protein levels of the Niemann-Pick C1-like 1 protein (NPC1L1) transporter, a
      LXRalpha target which regulates intestinal cholesterol absorption, were
      downregulated in EP 80317-treated mice. In contrast, neither mRNA nor protein
      levels of investigated transporters and receptors were modulated in the small
      intestine of double-deficient mice, nor was the fecal recovery of radioactivity.
      No change was observed in targeted genes in liver of either apoE- or apoE/CD36
      double-deficient mice after a chronic treatment with EP 80317. CONCLUSION: This
      study shows that EP 80317 elicits macrophage-to-feces reverse cholesterol
      transport in a manner dependent on CD36 expression. This effect is associated
      with the upregulation of LXRalpha and the downregulation of NPC1L1 expression.

PMID- 23880197
TI  - Effects of ezetimibe, simvastatin and ezetimibe/simvastatin on correlations
      between apolipoprotein B, LDL cholesterol and non-HDL cholesterol in patients
      with primary hypercholesterolemia.
AB  - BACKGROUND/SYNOPSIS: Apolipoprotein (apo) B is highly predictive of coronary
      risk, especially in patients with high triglycerides (TG). This post hoc analysis
      evaluated the effects of lipid-lowering therapy on correlations between apoB and
      low-density lipoprotein cholesterol (apoB:LDL-C) and non-high-density lipoprotein
      cholesterol (apoB:non-HDL-C) in patients with TG< and >= 200 mg/dL. METHODS: This
      analysis used data from 3 randomized clinical trials in patients with primary
      hypercholesterolemia receiving placebo, ezetimibe (EZE), simvastatin (SIMVA) or
      EZE/SIMVA for 12 weeks. Simple linear regression analyses predicted LDL-C and non
      HDL-C levels corresponding to apoB values (80 mg/dL) at baseline and Week 12.
      RESULTS: ApoB correlated with LDL-C (r >= 0.76) and non-HDL-C (r >= 0.86) at
      baseline. The correlations were strengthened with SIMVA and EZE/SIMVA at Week 12
      (r >= 0.88 for LDL-C and r >= 0.94 for non-HDL-C). The predicted LDL-C and non
      HDL-C values were lower following treatment with SIMVA or EZE/SIMVA than for
      placebo and EZE. For SIMVA and EZE/SIMVA, the predicted LDL-C and non-HDL-C
      values were closer to more aggressive LDL-C and non-HDL-C levels (i.e., 70 and
      100 mg/dL, respectively). The apoB:LDL-C and apoB:non-HDL-C correlations were
      weaker and the predicted LDL-C values were generally lower in high TG patients
      than in low TG patients both at baseline and Week 12. In contrast, the predicted
      non-HDL-C values were generally higher in high versus low TG patients at baseline
      but less so at Week 12. CONCLUSION: After treatment with EZE, SIMVA, or
      EZE/SIMVA, a given apoB value corresponds to lower LDL-C and non-HDL-C levels
      than those obtained from untreated patients.

PMID- 23880198
TI  - Abdominal adiposity largely explains associations between insulin resistance,
      hyperglycemia and subclinical atherosclerosis: the NEO study.
AB  - OBJECTIVE: The relative importance of insulin resistance and hyperglycemia to the
      development of atherosclerosis remains unclear. Furthermore, adiposity may be
      responsible for observed associations. Our aim was to study the relative
      contributions of adiposity, insulin resistance and hyperglycemia to subclinical
      atherosclerosis. METHODS: In this cross-sectional analysis of the Netherlands
      Epidemiology of Obesity (NEO) study, a cohort of persons of 45-65 years, BMI,
      waist circumference (WC), fasting glucose (FPG), HbA1c and insulin concentrations
      were measured and the revised HOMA-IR was calculated. The carotid Intima-Media
      Thickness (cIMT) was measured by ultrasound. We performed linear regression
      analyses between standardized values of FPG, HbA1c, HOMA-IR, BMI, WC with cIMT,
      and subsequently included age, sex, ethnicity, education and smoking, HOMA-IR,
      HbA1c and FPG, BMI and WC in the models. RESULTS: After exclusion of participants
      with glucose lowering therapy (n = 356) or missing data (n = 252), this analysis
      included 6065 participants, 43% men, and mean (SD) cIMT of 616 (92) MUm.
      Differences in cIMT (95% CI) per SD were: FPG: 16 (10,21); HbA1c: 12 (7,16); HOMA
      IR: 11 (6,16) MUm. These associations attenuated after adjustments, and
      attenuated most strongly after adjustment for WC. Differences in cIMT (95% CI)
      per SD in the full model were: FPG: 4 (0,7); HbA1c: 2 (-1,5); HOMA-IR: 0 (-3,3);
      BMI 16 (13,19); WC: 18 (14,21) MUm. CONCLUSION: In middle-aged individuals, we
      observed similar contributions of insulin resistance and hyperglycemia to
      subclinical atherosclerosis. These contributions were largely explained by
      abdominal adiposity, emphasizing the importance of weight management.

PMID- 23880199
TI  - Inhibition of monocyte chemotaxis by VB-201, a small molecule lecinoxoid, hinders
      atherosclerosis development in ApoE-/- mice.
AB  - OBJECTIVE: Monocytes are motile cells which sense inflammatory stimuli and
      subsequently migrate to sites of inflammation. Key players in host defense,
      monocytes have nevertheless been implicated as requisite mediators of several
      chronic inflammatory diseases. Inhibition of monocyte chemotaxis is therefore an
      attractive anti-inflammatory strategy. Oxidized phospholipids (OxPL) are native
      regulators of inflammation, yet their direct effect on monocyte chemotaxis is
      poorly defined. In this study, we investigated the direct effect of natural and
      synthetic phospholipids on monocyte chemotaxis. METHODS: Exploring various
      phospholipids using in vitro chemotaxis assays, we found that the natural
      phospholipid 1-palmitoyl-2-glutaryl phosphatidylcholine (PGPC) can decrease
      monocyte chemotaxis by 50%, while other tested OxPL had no effect. We generated a
      library of synthetic OxPL designated lecinoxoids, which was screened for anti
      inflammatory properties. RESULTS AND CONCLUSIONS: VB-201, a small-molecule
      lecinoxoid, exhibited up to 90% inhibition of monocyte chemotaxis in vitro.
      Molecular analysis revealed that the effect of VB-201 was not restricted to a
      specific chemotactic ligand or receptor, and resulted from inhibition of
      signaling pathways required for monocyte chemotaxis. Interestingly, VB-201 did
      not inhibit monocyte adhesion or phagocytosis and had no effect on chemotaxis of
      CD4(+) T-cells or neutrophils. In vivo, oral treatment with VB-201 reduced
      monocyte migration in a peritonitis model and inhibited atheroma development in
      ApoE(-/-) mice, without affecting cholesterol or triglyceride levels. Our
      findings highlight a novel role played by native and synthetic phospholipids in
      regulation of monocyte chemotaxis. The data strengthen the involvement of
      phospholipids as key signaling molecules in inflammatory settings and demonstrate
      their potential therapeutic applicability.

PMID- 23880200
TI  - Gut microbiota: an environmental risk factor for cardiovascular disease.

PMID- 23880201
TI  - Atherosclerotic plaque burden in cocaine users with acute chest pain: analysis by
      coronary computed tomography angiography.
AB  - Chest pain associated with cocaine use represents an increasing problem in the
      emergency department (ED). Cocaine use has been linked to the acute coronary
      syndrome (ACS) and acute myocardial infarction (AMI). We used coronary computed
      tomography angiography (cCTA) to evaluate the prevalence, severity and
      composition of atherosclerotic lesions in cocaine users. We studied 78 patients
      with non-occasional cocaine use (52 men, 44 +/- 7 years, 23 under the acute
      influence) and acute chest pain but without ACS, who had undergone cCTA in the
      ED. Patients were matched one-to-one by gender, race, symptoms, and risk-factors
      with a control cohort (n = 78; 52 men, 45 +/- 6 years) not using cocaine. Each
      coronary segment was evaluated for the presence and composition (calcified, non
      calcified, partially calcified) of atherosclerotic plaque and for stenosis. The
      prevalence of coronary stenosis was not significantly different between patients
      with and without cocaine use (13% versus 5%, P > 0.05). However, cocaine users on
      average had significantly more atherosclerotic plaques (0.44 +/- 0.88 versus 0.29
      +/- 0.83, P < 0.05) and a tendency towards more calcified (0.64 +/- 1.23 versus
      0.55 +/- 1.22, P > 0.05) and non-calcified plaques (0.26 +/- 0.63 versus 0.17 +/-
      0.57, P > 0.05), yet not reaching statistical significance. Furthermore, cocaine
      users had significantly more partially calcified plaques (0.41 +/- 0.61 versus
      0.17 +/- 0.41, P < 0.05) and higher partially calcified plaque volume (59.7 +/-
      33.3 mm(3) versus 25.6 +/- 12.6 mm(3), P < 0.05). Thus, cocaine users tend to
      have more pronounced coronary atherosclerosis compared to patients without
      cocaine use at the time of presentation with acute chest pain.

PMID- 23880202
TI  - HPS2-THRIVE results: bad for niacin/laropiprant, good for ezetimibe?

PMID- 23880203
TI  - Far wall pseudo-enhancement: a neglected artifact in carotid contrast-enhanced
      ultrasound?

PMID- 23880204
TI  - Insulin clearance is associated with carotid artery intima-media thickness.
AB  - OBJECTIVE: The aim of this study was to investigate whether insulin clearance is
      independently associated with carotid artery intima-media thickness (IMT), a well
      recognized index of vascular damage. METHODS: 361 Non-diabetic Caucasian subjects
      were subjected to euglycemic hyperinsulinemic clamp to assess insulin
      sensitivity, and insulin clearance. IMT of the common carotid was measured by
      ultrasonography. RESULTS: Among the study group, 270 subjects had normal glucose
      tolerance, 33 had impaired fasting glucose, and 58 had impaired glucose
      tolerance. Univariate correlations showed that age, BMI, waist, blood pressure,
      triglycerides, fasting and 2-h post-load glucose and insulin levels were
      positively correlated with carotid IMT whereas HDL, insulin clearance, and
      insulin-stimulated glucose disposal were negatively correlated with IMT. A
      multivariate regression analysis in a model including, in addition to insulin
      clearance, age, gender, BMI, waist, blood pressure, triglycerides, HDL, fasting
      and 2-h post-load glucose, insulin-stimulated glucose disposal, fasting and 2-h
      post-load insulin showed that the traits independently associated with carotid
      IMT were BMI (beta = 0.42, P < 0.0001), insulin clearance (beta = -0.29, P <
      0.0001), age (beta = 0.19, P < 0.0001), waist (beta = 0.18, P = 0.01), diastolic
      blood pressure (beta = 0.17, P = 0.01), and 2-h post-load glucose (beta = 0.12, P
      = 0.03). These factors explained 26% of the variance in carotid IMT. Subjects in
      the lowest tertile of insulin clearance had a 4.06-fold higher odds of having
      vascular damage (IMT > 0.9 mm) as compared with those in the highest tertile (OR
      4.06, 95%CI 1.15-13.24). CONCLUSIONS: Insulin clearance is independently
      associated with carotid IMT in adult non-diabetic subjects. Individuals with
      lower levels of insulin clearance have a higher odds of vascular damage.

PMID- 23880205
TI  - Pseudo-enhancement does not explain the increased carotid adventitial vasa
      vasorum signal in diabetic patients.

PMID- 23880206
TI  - In stent restenosis and thrombosis assessment after EP224283 injection in a rat
      model.
AB  - OBJECTIVE: After stent implantation, platelet aggregation and thrombus formation
      are thought to play a key role in the early phase of in-stent restenosis (ISR).
      Drug-eluting stents have reduced ISR, but are associated with healing-related
      issues or hypersensitivity reactions, leading to an increased risk of late acute
      stent thrombosis. EP224283 is a new dual-action antithrombotic molecule combining
      a GPIIbIIIa antagonist and a factor Xa inhibitor. We investigated its efficacy on
      restenosis in a rat model of ISR and on platelet adhesion. METHODS AND RESULTS:
      Rat aortas were stented and the animals received either EP224283 or vehicle
      subcutaneously every 48 h. At day 7 and day 28 after surgery, the stented aortas
      were removed and processed for morphometric analysis or protein analysis. At day
      28, EP224283 significantly reduced neointima growth (in the range of 20%).
      Protein analysis revealed that EP224283 reduced cell proliferation pathways:
      ERK1/2 and Akt were down-regulated and p38 up-regulated. Expression of Ki67 was
      also reduced. In vitro assessment depicted a reduction of platelet activation and
      platelet adhesion among treated rats. CONCLUSION: These results show a beneficial
      effect of EP224283 on in-stent restenosis and on stent thrombogenicity that may
      improve results after stent implantation. Further investigations are required to
      assess the efficacy of a local delivery of EP224283 on both acute thrombosis and
      ISR.

PMID- 23880207
TI  - The association of relative telomere length with symptomatic peripheral arterial
      disease: results from the CAVASIC study.
AB  - BACKGROUND AND OBJECTIVES: Short telomere length has been described to be
      associated with biological aging including atherosclerosis phenotypes. However,
      information in patients with symptomatic peripheral arterial disease (PAD) is
      sparse. We therefore aimed to investigate whether inter-individual differences in
      relative telomere length (RTL) are associated with symptomatic PAD. DESIGN: We
      measured RTL by a quantitative PCR method in the CAVASIC Study, a cohort of 241
      male Caucasian patients diagnosed with intermittent claudication and 249 age- and
      diabetes-matched controls. RESULTS: We observed significantly shorter mean RTL in
      patients than in controls (1.24 +/- 0.19 vs. 1.32 +/- 0.23, p < 0.001). Each
      shortening of RTL by one standard deviation significantly increased the odds for
      PAD by 44%: age-adjusted OR = 1.44 (95%CI 1.19-1.75, p < 0.001). This association
      remained significant after additional adjustment for log-C-reactive protein,
      glomerular filtration rate, HDL cholesterol, current smoking and log N-terminal
      pro-B-type natriuretic peptide (NT-proBNP). Excluding patients with prevalent
      cardiovascular disease revealed very similar results. When we compared the model
      fit of the various adjustment models including cardiac risk factors and/or NT
      proBNP the addition of RTL significantly improved discrimination between patients
      and controls. CONCLUSION: This study in a male cohort of patients with
      intermittent claudication and age- and diabetes-matched controls indicates a
      significant association of shorter relative telomere length with PAD. Our results
      reinforce RTL as a marker for PAD that reflects the influence of genetic and
      environmental risk factors. Moreover, the association remains significant after
      excluding patients and controls free from prevalent cardiovascular disease.

PMID- 23880208
TI  - Circulating osteopontin as a marker of early coronary vascular calcification in
      type two diabetes mellitus patients with known asymptomatic coronary artery
      disease.
AB  - OBJECTIVE: To evaluate the interrelation between circulating osteopontin (OPN)
      and coronary atherosclerosis and calcification in type 2 diabetes mellitus
      patients (T2DM). DESIGN AND METHODS: 126 subjects (46 patients with T2DM) with
      previously documented asymptomatic coronary artery disease (CAD) were enrolled in
      the study. CAD was determined by contrast multispiral CT-angiography. OPN plasma
      levels were measured by ELISA. RESULTS: Analysis of the results showed that in a
      patient cohort the mean value of circulating OPN was 43.55 ng/mL (95% CI = 31.5
      57.0 ng/mL). OPN plasma levels were correlated with Agatston score index (r =
      0.418, P = 0.009), T2DM (r = 0.411, P = 0.006), gender (r = 0.395, P < 0.001 for
      male), TC (r = 0.405, P = 0.006), hsC-RP (r = 0.368, P = 0.008), age (r = 0.256,
      P = 0.001), smoking (r = 0.255, P = 0.001) and inversely to LVEF (r = -0.579, P =
      0.001). Cox-regression analyzes showed that in T2DM patients upper quartile OPN
      compared with the lowest quartile are associated with Agatston score index
      (adjusted OR = 3.23, 95% CI = 1.09-5.20; P = 0.044), numerous of damaged coronary
      arteries (adjusted OR = 2.60, 95% CI = 1.10-9.20, P = 0.005). The findings
      suggest that the predictive power of the model for asymptomatic CAD patients with
      T2DM, the estimated AUC (area under curve) was 0.788. In this case, the
      concentration of OPN that had the best predict potential on the risk of coronary
      atherosclerosis was 48.5 ng/mL. In conclusions, we believe that elevated OPN in
      plasma can be considered as an independent predictor of coronary calcification in
      T2DM patients with known CAD.

PMID- 23880209
TI  - The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot
      study.
AB  - BACKGROUND: The gene product of the ABCB1 gene, the P-glycoprotein, functions as
      a custodian molecule in the blood-brain barrier and regulates the access of most
      antidepressants into the brain. Previous studies showed that ABCB1 polymorphisms
      predicted the response to antidepressants that are substrates of the P-gp, while
      the response to nonsubstrates was not influenced by ABCB1 polymorphisms. The aim
      of the present study was to evaluate the clinical application of ABCB1 genotyping
      in antidepressant pharmacotherapy. METHODS: Data came from 58 depressed
      inpatients participating in the Munich Antidepressant Response Signature (MARS)
      project, whose ABCB1 gene test results were implemented into the clinical
      decision making process. Hamilton Depression Rating Scale (HAM-D) scores,
      remission rates, and duration of hospital stay were documented with dose and kind
      of antidepressant treatment. RESULTS: Patients who received ABCB1 genotyping had
      higher remission rates [chi2(1) = 6.596, p = 0.005, 1-sided] and lower Hamilton
      sores [t(111) = 2.091, p = 0.0195, 1-sided] at the time of discharge from
      hospital as compared to patients without ABCB1 testing. Among major allele
      homozygotes for ABCB1 single nucleotide polymorphisms (SNPs) rs2032583 and
      rs2235015 (TT/GG genotype), an increase in dose was associated with a shorter
      duration of hospital stay [rho(28) = -0.441, p = 0.009, 1-sided], whereas other
      treatment strategies (eg, switching to a nonsubstrate) showed no significant
      associations with better treatment outcome. Discussion The implementation of
      ABCB1 genotyping as a diagnostic tool influenced clinical decisions and led to an
      improvement of treatment outcome. Patients carrying the TT/GG genotype seemed to
      benefit from an increase in P-gp substrate dose. CONCLUSION: Results suggest that
      antidepressant treatment of depression can be optimized by the clinical
      application of ABCB1 genotyping.

PMID- 23880210
TI  - Polymorphisms in genes related to inflammation, NSAID use, and the risk of
      prostate cancer among Danish men.
AB  - The etiology of prostate cancer (PC) remains mostly unknown, but increasing
      evidence suggests that chronic inflammation in the prostate is associated with an
      increased risk of PC. Epidemiological studies have suggested that use of
      nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against PC. Inborn
      variations in genes involved in the inflammatory response may modulate the risk
      of PC and interact with NSAIDs. The aims of this study were 1) to evaluate
      whether polymorphisms and haplotypes of the inflammation-related genes COX-2,
      Il1B, NFKB1, and PPARG are associated with risk of PC; 2) to investigate gene
      environment interactions between polymorphisms and NSAID use; and 3) to examine
      whether the studied polymorphisms were associated with the aggressiveness of PC.
      The study population consisted of 370 cases of PC and 370 risk-set matched (age)
      controls nested within the prospective Danish "Diet, Cancer, and Health" cohort.
      Carriers of the variant deletion allele of NFKB1 -94ins/delATTG had a tendency
      toward a reduced risk of PC (incidence rate ratio (IRR), 0.73; 95% confidence
      interval (CI) 0.52-1.04). A lowered risk for PC was also found for carriers of
      variant allele NFKB1 -94ins/delATTG among non-users of NSAIDs (IRR 0.68; 95% CI
      0.47-0.99), for non-aggressive disease (IRR 0.64; 95% CI 0.42-0.99), and among
      men with a body mass index above 30 kg/m(2) (IRR 0.56; 95% CI 0.27-1.16),
      although the latter estimate was based on small numbers. A similar pattern was
      seen for the variant C allele of the COX-2 +8473T->C polymorphism. No apparent
      association with PC was observed for the other studied polymorphisms. Our study
      did not indicate that chronic inflammation is a major risk factor for aggressive
      PC. 

PMID- 23880211
TI  - The importance of codon context for understanding the Ig-like somatic
      hypermutation strand-biased patterns in TP53 mutations in breast cancer.
AB  - Evidence already exists that the activation-induced deaminase (AID)/APOBEC family
      constitutes a set of differentially expressed enzymes capable of deaminating
      cytosines (C to U) in single-stranded DNA (ssDNA) and that they are potentially
      powerful mutagens. The mutagenic processes involved are believed to be activated
      in many nonlymphoid tissue types-for example, initiating some cancers and/or
      leading to further somatic mutagenesis. To investigate the extent that codon
      context might be important in influencing the likely location of TP53 mutations
      in breast cancer, the codon-bias patterns resulting from the ssDNA target
      specificities of cytidine deaminases of the AID/APOBEC family were analyzed. The
      data indicate that codon context strongly influences the likely location of
      mutations at motifs for AID/APOBEC1/APOBEC3G, and at WA sites. An unexpected
      finding is a highly significant preference for transitions of cytosine to occur
      at the first nucleotide position and for transitions of guanosine to occur at the
      second nucleotide position in the mutated codon (read 3' to 5'). Thus, the
      mechanisms involved appear to be sensitive to codon reading frames and to have an
      intrinsic ability to differentiate between the cytosines on the nontranscribed
      strand and those on the transcribed strand in the context of an open
      "transcription bubble." 

PMID- 23880212
TI  - Etiologies, diagnostic strategies, and outcomes of diffuse pulmonary infiltrates
      causing acute respiratory failure in cancer patients: a retrospective
      observational study.
AB  - INTRODUCTION: Although previous studies have reported etiologies, diagnostic
      strategies, and outcomes of acute respiratory failure (ARF) in cancer patients,
      few studies investigated ARF in cancer patients presenting with diffuse pulmonary
      infiltrates. METHODS: This was a retrospective observational study of 214
      consecutive cancer patients with diffuse pulmonary infiltrates on chest
      radiography admitted to the oncology medical intensive care unit for acute
      respiratory failure between July 2009 and June 2011. RESULTS: After diagnostic
      investigations including bronchoalveolar lavage in 160 (75%) patients,
      transbronchial lung biopsy in 75 (35%), and surgical lung biopsy in 6 (3%), the
      etiologies of diffuse pulmonary infiltrates causing ARF were identified in 187
      (87%) patients. The most common etiology was infection (138, 64%), followed by
      drug-induced pneumonitis (13, 6%) and metastasis (12, 6%). Based on the etiologic
      diagnoses, therapies for diffuse pulmonary infiltrates were subsequently modified
      in 99 (46%) patients. Diagnostic yield (46%, 62%, 85%, and 100%; P for trend <
      0.001) and frequency of therapeutic modifications (14%, 37%, 52%, and 100%; P for
      trend < 0.001) were significantly increased with additional invasive tests.
      Patients with therapeutic modification had a 34% lower in-hospital mortality rate
      than patients without therapeutic modification (38% versus 58%, P = 0.004) and a
      similar difference in mortality rate was observed up to 90 days (55% versus 73%,
      Log-rank P = 0.004). After adjusting for potential confounding factors,
      therapeutic modification was still significantly associated with reduced in
      hospital mortality (adjusted OR 0.509, 95% CI 0.281-0.920). CONCLUSIONS: Invasive
      diagnostic tests, including lung biopsy, increased diagnostic yield and caused
      therapeutic modification that was significantly associated with better outcomes
      for diffuse pulmonary infiltrates causing ARF in cancer patients.

PMID- 23880213
TI  - Combined effects of modafinil and d-amphetamine in male Sprague-Dawley rats
      trained to discriminate d-amphetamine.
AB  - Modafinil is a novel wake-promoting drug with FDA approval for the treatment of
      sleep-related disorders that has recently been investigated as a potential
      agonist replacement therapy for psychostimulant dependence. Previous research in
      animals and humans indicates modafinil has a lower abuse liability than
      traditional psychostimulants, although few studies have carefully assessed
      modafinil's stimulus properties in combination with other psychostimulants. The
      current study trained male Sprague-Dawley rats to discriminate subcutaneous
      injections of 0.3 mg/kg (n=8) or 1.0 mg/kg d-amphetamine (n=8) from saline under
      an FR 20 schedule of food reinforcement and substitution tests were administered
      with d-amphetamine (0.03-1.0 mg/kg, s.c.), modafinil (32-256 mg/kg, i.g.), and a
      low modafinil dose (32 mg/kg, i.g.) in combination with d-amphetamine (0.03-1.0
      mg/kg, s.c.) to determine if these drugs have additive effects. The selective D2
      dopamine agonist, PNU-91356A, was also tested as a positive control and ethanol
      and morphine were tested as negative controls. Results indicate that modafinil
      produced dose-dependent and statistically significant d-amphetamine-lever
      responding in both groups and nearly complete substitution in animals trained to
      discriminate 1.0 mg/kg d-amphetamine. Modafinil pretreatment slightly increased
      the discrimination of low d-amphetamine doses in animals trained to discriminate
      0.3 mg/kg d-amphetamine. These results support previous findings that modafinil
      and d-amphetamine may have additive effects. In consideration of recent interests
      in modafinil as an agonist treatment for psychostimulant dependence, additional
      preclinical investigations utilizing other methodologies to examine modafinil in
      combination with other stimulants, such as behavioral sensitization paradigms or
      drug self-administration, may be of interest.

PMID- 23880215
TI  - Evaluation of molecular community analysis methods for discerning fecal sources
      and human waste.
AB  - Molecular microbial community analyses provide information on thousands of
      microorganisms simultaneously, and integrate biotic and abiotic perturbations
      caused by fecal contamination entering water bodies. A few studies have explored
      community methods as emerging approaches for microbial source tracking (MST),
      however, an evaluation of the current state of this approach is lacking. Here, we
      utilized three types of community-based methods with 64 blind, single- or dual
      source, challenge samples generated from 12 sources, including: humans (feces),
      sewage, septage, dogs, pigs, deer, horses, cows, chickens, gulls, pigeons, and
      geese. Each source was a composite from multiple donors from four representative
      geographical regions in California. Methods evaluated included terminal
      restriction fragment polymorphism (TRFLP), phylogenetic microarray (PhyloChip),
      and next generation (Illumina) sequencing. These methods correctly identified
      dominant (or sole) sources in over 90% of the challenge samples, and exhibited
      excellent specificity regardless of source, rarely detecting a source that was
      not present in the challenge sample. Sensitivity, however, varied with source and
      community analysis method. All three methods distinguished septage from human
      feces and sewage, and identified deer and horse with 100% sensitivity and 100%
      specificity. Method performance improved if the composition of blind dual-source
      reference samples were defined by DNA contribution of each single source within
      the mixture, instead of by Enterococcus colony forming units. Data analysis
      approach also influenced method performance, indicating the need to standardize
      data interpretation. Overall, results of this study indicate that community
      analysis methods hold great promise as they may be used to identify any source,
      and they are particularly useful for sources that currently do not have, and may
      never have, a source-specific single marker gene. 

PMID- 23880216
TI  - Modelling and understanding the competitive adsorption of microcystins and tannic
      acid.
AB  - A predictive model integrating adsorption kinetics and competitive isotherm
      models (Homogeneous Surface Diffusion Model, Freundlich-type and Fritz &
      Schlunder isotherms) was developed to describe and understand the competing
      mechanism(s) and the ionic strength (IS) role on microcystins (MC) and tannic
      acid (TA) competitive adsorption. The developed model showed good agreement with
      the experimental data obtained from batch adsorption tests and isotherms
      conducted with MC extracts and TA model solutions (single-solute and
      multicomponent, IS presence and absence) using a mesoporous powdered activated
      carbon (PAC). Results confirm that similar size molecules such as MC and TA are
      strong competitors and tannin-rich waters may severely affect MC residuals in the
      treated water. Unlike usually considered, both direct site and pore blockage
      mechanisms seem relevant. Competition effects appear to be more dependent on the
      competitor/contaminant molar ratio than on the initial concentrations. The IS
      affects the extent and the mechanisms of MC-TA competitive adsorption, reducing
      PAC dose for safe control of MC residuals. The developed model, including a Ds
      analysis, is an important tool to understand the competitive adsorption of
      similar size adsorbates. 

PMID- 23880217
TI  - Investigating norovirus removal by microfiltration, ultrafiltration, and
      precoagulation-microfiltration processes using recombinant norovirus virus-like
      particles and real-time immuno-PCR.
AB  - The removal of microorganisms by drinking water treatment processes has been
      widely investigated in laboratory-scale experiments using artificially propagated
      microorganisms. However, this approach cannot be applied to norovirus removal,
      because this virus does not grow in cell or organ culture, and this fact has
      hampered our ability to investigate its behavior during drinking water treatment.
      To overcome this difficulty, our research group previously used recombinant
      norovirus virus-like particles (rNV-VLPs), which consist of an artificially
      expressed norovirus capsid protein, in laboratory-scale drinking water treatment
      experiments. However, the enzyme-linked immunosorbent assay (ELISA) method
      generally used to detect rNV-VLPs is not sensitive enough to evaluate high
      removal ratios such as those obtained by ultrafiltration (UF). We therefore
      developed and applied a real-time immuno-polymerase chain reaction (iPCR) assay
      for rNV-VLP quantification to investigate norovirus removal by microfiltration
      (MF), UF, and hybrid precoagulation-MF processes. The rNV-VLP detection limit
      with the developed iPCR assay was improved at least 1000-fold compared with
      ELISA. Whereas MF with a nominal pore size of 0.1 MUm could not eliminate NV
      VLPs, a 4-log reduction was achieved by UF with a molecular weight cutoff of 1
      kDa. When MF was combined with precoagulation (>=10 MUmol-Fe/L for ferric
      chloride; >=20 MUmol-Al/L for polyaluminum chloride; >=40 MUmol-Al/L for alum),
      the performance of the hybrid process in eliminating rNV-VLPs was greater than
      that achieved by the 1 kDa UF. For all processes, the removal ratios of the
      bacteriophages MS2 and Qbeta were greater than the rNV-VLP removal ratios by 1-2
      logs, so neither bacteriophage can be recommended as a possible conservative
      surrogate for predicting the behavior of native NV during these processes.

PMID- 23880214
TI  - Prenatal and gestational cocaine exposure: Effects on the oxytocin system and
      social behavior with implications for addiction.
AB  - Drug abuse during pregnancy is a major public health concern, with negative
      consequences throughout development. Prenatal cocaine exposure (PCE) in rats
      produces social behavior deficits with corresponding changes in neuroendocrine
      and monoaminergic signaling. The relevance of parental care in social behavior
      maturity cannot be ignored, and gestational exposure to cocaine severely disrupts
      parental care, thus impacting the early environment of the offspring. Oxytocin
      (Oxt) is critical in regulating social behaviors and central levels are disrupted
      following acute and chronic cocaine (CC) treatment in postpartum rat dams,
      coincident with deficits in maternal care. We will discuss studies aimed to
      determine the relative contribution of PCE and CC-induced deficits in maternal
      care to social behaviors and Oxt signaling across development. PCE results in
      decreased social (including parental) behaviors in adolescence and adulthood. PCE
      is also associated with increased aggression in adults. Rearing by CC-exposed
      mothers synergistically increases the behavioral effects of PCE. Rearing by CC
      exposed mothers, but not PCE, disrupts Oxt levels and mRNA in regions relevant to
      social behavior, but does not affect receptors in postpartum adult offspring.
      Preliminary work indicates that PCE/CC rearing has dynamic effects on Oxt levels
      and receptors in neonatal rat pups, suggesting very early regulation of Oxt
      signaling. This work highlights how the interactive role of Oxt signaling and
      behavioral context throughout development can be derailed by drug abuse during
      pregnancy. The relevance of disrupted Oxt to intergenerational transmission of
      addiction is briefly discussed. 

PMID- 23880218
TI  - Performance of forty-one microbial source tracking methods: a twenty-seven lab
      evaluation study.
AB  - The last decade has seen development of numerous new microbial source tracking
      (MST) methodologies, but many of these have been tested in just a few
      laboratories with a limited number of fecal samples. This method evaluation study
      examined the specificity and sensitivity of 41 MST methodologies by analyzing
      data generated in 27 laboratories. MST methodologies that targeted human, cow,
      ruminant, dog, gull, pig, horse, and sheep were tested against sewage, septage,
      human, cow, dog, deer, pig, chicken, pigeon, gull, horse, and goose fecal
      samples. Each laboratory received 64 blind samples containing a single source
      (singletons) or two sources (doubletons), as well as diluted singleton samples to
      assess method sensitivity. Laboratories utilized their own protocols when
      performing the methods and data were deposited in a central database before
      samples were unblinded. Between one and seven laboratories tested each method.
      The most sensitive and specific assays, based on an analysis of presence/absence
      of each marker in target and non-target fecal samples, were HF183 endpoint and
      HF183SYBR (human), CF193 and Rum2Bac (ruminant), CowM2 and CowM3 (cow), BacCan
      (dog), Gull2SYBR and LeeSeaGull (gull), PF163 and pigmtDNA (pig), HoF597 (horse),
      PhyloChip (pig, horse, chicken, deer), Universal 16S TRFLP (deer), and
      Bacteroidales 16S TRFLP (pig, horse, chicken, deer); all had sensitivity and
      specificity higher than 80% in all or the majority of laboratories. When the
      abundance of MST markers in target and non-target fecal samples was examined,
      some assays that performed well in the binary analysis were found to not be
      sensitive enough as median concentrations fell below a minimum abundance
      criterion (set at 50 copies per colony forming units of enterococci) in target
      fecal samples. Similarly, some assays that cross-reacted with non-target fecal
      sources in the binary analysis were found to perform well in a quantitative
      analysis because the cross-reaction occurred at very low levels. Based on a
      quantitative analysis, the best performing methods were HF183Taqman and BacH
      (human), Rum2Bac and BacR (ruminant), LeeSeaGull (gull), and Pig2Bac (pig); no
      cow or dog-specific assay met the quantitative specificity and sensitivity
      criteria. Some of the best performing assays in the study were run by just one
      laboratory so further testing of assay portability is needed. While this study
      evaluated the marker performance in defined samples, further field testing as
      well as development of frameworks for fecal source allocation and risk assessment
      are needed. 

PMID- 23880219
TI  - Bacteroidales terminal restriction fragment length polymorphism (TRFLP) for fecal
      source differentiation in comparison to and in combination with universal
      bacteria TRFLP.
AB  - Terminal restriction fragment length polymorphism (TRFLP) is an attractive
      community analysis method for microbial source tracking (MST) because it is
      accessible, relatively inexpensive, and can discern multiple fecal sources
      simultaneously. A new Bacteroidales TRFLP (Bac-TRFLP) method was developed and
      its source identification performance was evaluated by itself, in comparison to,
      and in combination with an existing universal bacterial TRFLP method in two
      laboratories. Sixty-four blind samples from 12 fecal sources (sewage, septage,
      human, dog, horse, cow, deer, pig, chicken, goose, pigeon, and gull) were used
      for evaluation. Bac- and Univ-TRFLP exhibited similarly high overall correct
      identification (>88% and >89%, respectively), excellent specificity regardless of
      fecal sources, variable sensitivity depending on the source, and stable
      performance across two laboratories. Compared to Univ-TRFLP, Bac-TRFLP had better
      sensitivity and specificity with horse, cow, and pig fecal sources but was not
      suited for certain avian sources such as goose, gull, and pigeon. Combining the
      general and more targeted TRFLP methods (Univ&Bac-TRFLP) achieved higher overall
      correct identification (>92%), higher sensitivity and specificity metrics, and
      higher reproducibility between laboratories. Our results suggest that the Bac
      TRFLP and Univ&Bac-TRFLP methods are promising additions to the MST toolbox and
      warrant further evaluation and utilization in field MST applications. 

PMID- 23880221
TI  - Genome-wide association study in breast cancer survivors reveals SNPs associated
      with gene expression of genes belonging to MHC class I and II.
AB  - INTRODUCTION: We investigated the effect of genetic variation on gene expression
      in blood from a cohort of BC survivors. Further, we investigated the associations
      that were specific for BC survivors by performing identical analyses for a group
      of healthy women and comparing the results. METHODS: eQTL analysis was performed
      for 288 BC survivors (full data set). Further, using a subset of the data, eQTL
      analyses were performed on 288 BC survivors and on 81 healthy women separately
      and results were compared. RESULTS: A large number of associations were observed
      for the BC survivors, and the expression of human leukocyte antigen genes was
      found associated with SNPs in 100 genes. The comparison analyses with healthy
      women revealed associations occurring specifically in BC survivors, and the genes
      showed enrichment for immune system processes. CONCLUSIONS: The results suggest
      that the immune system has a different constitution in BC survivors compared to
      healthy women.

PMID- 23880220
TI  - Identification of the feline foamy virus Bet domain essential for APOBEC3
      counteraction.
AB  - BACKGROUND: APOBEC3 (A3) proteins restrict viral replication by cytidine
      deamination of viral DNA genomes and impairing reverse transcription and
      integration. To escape this restriction, lentiviruses have evolved the viral
      infectivity factor (Vif), which binds A3 proteins and targets them for
      proteolytic degradation. In contrast, foamy viruses (FVs) encode Bet proteins
      that allow replication in the presence of A3, apparently by A3 binding and/or
      sequestration, thus preventing A3 packaging into virions and subsequent
      restriction. Due to a long-lasting FV-host coevolution, Bet proteins mainly
      counteract restriction by A3s from their cognate or highly related host species.
      RESULTS: Through bioinformatics, we identified conserved motifs in Bet, all
      localized in the bel2 exon. In line with the localization of these conserved
      motifs within bel2, this part of feline FV (FFV) Bet has been shown to be
      essential for feline A3 (feA3) inactivation and feA3 protein binding. To study
      the function of the Bet motifs in detail, we analyzed the ability of targeted
      deletion, substitution, and chimeric FFV-PFV (prototype FV) Bet mutants to
      physically bind and/or inactivate feA3. Binding of Bet to feA3Z2b is sensitive to
      mutations in the first three conserved motifs and N- and C-terminal deletions and
      substitutions across almost the complete bel2 coding sequence. In contrast, the
      Bel1 (also designated Tas) domain of Bet is dispensable for basal feA3Z2b
      inactivation and binding but mainly increases the steady state level of Bet.
      Studies with PFV Bel1 and full-length FFV Bel2 chimeras confirmed the importance
      of Bel2 for A3 inactivation indicating that Bel1 is dispensable for basal feA3Z2b
      inactivation and binding but increases Bet stability. Moreover, the bel1/tas exon
      may be required for expression of a fully functional Bet protein from a spliced
      transcript. CONCLUSIONS: We show that the Bel2 domain of FV Bet is essential for
      the inactivation of APOBEC3 cytidine deaminase restriction factors. The Bel1/Tas
      domain increases protein stability and can be exchanged by related sequence.
      Since feA3 binding and inactivation by Bet are highly correlated, the data
      support the view that FV Bet prevents A3-mediated restriction of viral
      replication by creating strong complexes with these proteins.

PMID- 23880222
TI  - RepEx: repeat extractor for biological sequences.
AB  - Genomic sequences are far from being random but are made up of systematically
      ordered and information rich patterns. These repeated sequence patterns have been
      vastly utilized for their fundamental importance in understanding the genome
      function and organization. To this end, a comprehensive toolkit, RepEx, has been
      developed which extracts repeat (inverted, everted and mirror) patterns from the
      given genome sequence(s) without any constraints. The toolkit can also be used to
      fetch the inverted repeats present in the protein sequence(s). Further, it is
      capable of extracting exact and degenerate repeats with a user defined spacer
      intervals. It is remarkably more precise and sensitive when compared to the
      existing tools. An example with comprehensive case studies and a performance
      evaluation of the proposed toolkit has been presented to authenticate its
      efficiency and accuracy. 

PMID- 23880223
TI  - Multifocal enlargement and increased vascularization of peripheral nerves
      detected by sonography in CIDP: a pilot study.
AB  - OBJECTIVE: Detection of nerve enlargement in polyneuropathies by sonography is a
      new research area. No systematic investigation has been done yet in chronic
      inflammatory demyelinating polyneuropathy (CIDP). Therefore we investigated this
      in CIDP. METHODS: Eleven patients with CIDP fulfilling the international criteria
      on CIDP underwent ultrasonographic examination of the median, ulnar, fibular and
      posterior tibial nerves and sometimes the brachial plexus bilaterally, using a
      standardized protocol. We assessed presence of nerve thickening and increased
      nerve vascularization. RESULTS: In 7 of the 11 patients multiple nerve
      enlargements were detected: ulnar nerve 7, fibular nerve 5, posterior tibial
      nerve 4 and median nerve in 4 patients. The number of enlarged nerves was related
      with the MRC sum-score (p=0.03) and the total protein in the cerebrospinal fluid
      (CSF) at diagnosis (p=0.02). Increased vascularization was seen in 6 of the 11
      patients: 4 in one nerve and in 2 in multiple nerves. The number of nerves with
      increased vascularization was associated with the number of enlarged nerves
      (p=0.01) and total protein in the CSF (p=0.006). CONCLUSION: Multiple nerve
      enlargements occur in CIDP showing a relation with a lower MRC sum-score,
      increased nerve vascularization and a higher total protein of the CSF.
      SIGNIFICANCE: Our findings of nerve enlargement and increased nerve
      vascularization may be tools to monitor disease activity in CIDP, but further
      studies are needed.

PMID- 23880224
TI  - The 1,3-dipolar cycloaddition reaction of chiral carbohydrate-derived nitrone and
      olefin: towards long-chain sugars.
AB  - The thermal and microwave-activated 1,3-dipolar cycloadditions of several
      alpha,beta-unsaturated esters derived from d-mannose and chiral nitrones derived
      from threitol have been studied as a model reaction en route to eleven carbon
      long chain carbohydrates. Very high facial selectivity is observed for the chiral
      nitrones whereas the olefin facial selectivity varies with the substrate. The
      presence of a dioxolane ring alpha to the olefinic bond is beneficial to the
      facial selectivity of the olefin whereas a pyranose ring is not. The combination
      of a d-mannose derivative and a l-threitol-derived nitrone is a matched pair
      suitable for the synthesis of long chain sugars with nine contiguous chiral
      centres. Finally complete facial selectivity was observed with exo-glycals which
      gave a single cycloadduct. 

PMID- 23880225
TI  - Hemorrhagic cystitis in children treated with alkylating agent cyclophosphamide:
      The experience of a medical center in Taiwan.
AB  - BACKGROUND/PURPOSE: Hemorrhagic cystitis is a common complication with
      chemotherapeutic alkylating agents. We investigated the possible prognostic
      factors of cyclophosphamide-induced hemorrhagic cystitis in children. METHODS:
      Medical records of children (< 18 years old) with cyclophosphamide-related
      hemorrhagic cystitis were collected retrospectively from January 2000 to December
      2010 in a tertiary care center. We also prospectively enrolled children (< 18
      years old) with cyclophosphamide treatment. RESULTS: The retrospective study
      consisted of 23 patients whose median age was 11 years. The median day of onset
      time was 1 day after cyclophosphamide usage. The hemato-oncological diseases
      included acute leukemia (39.1%), lymphoma (13%), blastoma (13%), sarcoma (13%),
      aplastic anemia (13%), and others (8.7%). Patients who received bone marrow
      transplantation (BMT) had significantly longer duration of hemorrhagic cystitis
      than those who did not receive BMT (p < 0.05). Serum uric acid, checked prior to
      and after the onset of hemorrhage cystitis, was significantly lower after the
      development of hemorrhagic cystitis (p < 0.05). In the prospective study, 11
      children were enrolled with a median age of 5 years. The urinary nitrite/nitrate
      and 8-iso-prostaglandin F2alpha levels increased significantly after
      cyclophosphamide usage (p < 0.05). CONCLUSION: Alteration serum uric acid level
      and BMT could be indicators for severe hemorrhagic cystitis. The elevated levels
      of urinary nitrite/nitrate and 8-iso-prostaglandin F2alpha may indicate the
      essential roles played by nitric oxide syntheses and reactive oxidative stress in
      cyclophosphamide-induced hemorrhagic cystitis. These findings may help clinicians
      formulate a better strategy for treating cyclophosphamide-induced hemorrhagic
      cystitis.

PMID- 23880227
TI  - The effects of hedgehog on RNA binding protein Msi1 during the osteogenic
      differentiation of human cord blood-derived mesenchymal stem cells.
AB  - Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) are useful
      tools for regenerative medicine due to their capacity for self-renewal and multi
      lineage differentiation. The appropriate clinical application of MSCs for
      regenerative medicine requires an integrated understanding of multiple signaling
      pathways that regulate cell proliferation, stemness and differentiation. However,
      the potential molecular mechanisms mediating these functions are not completely
      understood. The effects of hedgehog (Hh) signaling on the osteogenic
      differentiation of MSCs are still controversial, and the underlying mechanisms
      are unclear. In the present study, we evaluated the direct effects of Hh
      signaling on the osteogenic differentiation of hUCB-MSCs and investigated
      potential downstream regulatory mechanisms responsible for Hh signaling. We
      observed that Hh signaling acts as a negative regulator of osteogenic
      differentiation through the suppression of RNA-binding Msi1, which in turn
      suppresses the expression of Wnt1 and the miR-148 family, especially miR-148b.
      Moreover, Hh and Msi1 are considered to be potential stemness markers of hUCB
      MSCs due to their differentiation-dependent expression profiles. This study
      provides new insights into mechanisms regulating MSC differentiation and may have
      implications for a variety of therapeutic applications in the clinic. 

PMID- 23880226
TI  - Morphological and genetic diversity of Rhipicephalus sanguineus sensu lato from
      the New and Old Worlds.
AB  - BACKGROUND: The taxonomic status of the brown dog tick (Rhipicephalus sanguineus
      sensu stricto), which has long been regarded as the most widespread tick
      worldwide and a vector of many pathogens to dogs and humans, is currently under
      dispute. METHODS: We conducted a comprehensive morphological and genetic study of
      278 representative specimens, which belonged to different species (i.e.,
      Rhipicephalus bursa, R. guilhoni, R. microplus, R. muhsamae, R. pusillus, R.
      sanguineus sensu lato, and R. turanicus) collected from Europe, Asia, Americas,
      and Oceania. After detailed morphological examination, ticks were molecularly
      processed for the analysis of partial mitochondrial (16S rDNA, 12S rDNA, and
      cox1) gene sequences. RESULTS: In addition to R. sanguineus s.l. and R.
      turanicus, three different operational taxonomic units (namely, R. sp. I, R. sp.
      II, and R. sp. III) were found on dogs. These operational taxonomical units were
      morphologically and genetically different from R. sanguineus s.l. and R.
      turanicus. Ticks identified as R. sanguineus s.l., which corresponds to the so
      called "tropical species" (= northern lineage), were found in all continents and
      genetically it represents a sister group of R. guilhoni. R. turanicus was found
      on a wide range of hosts in Italy and also on dogs in Greece. CONCLUSIONS: The
      tropical species and the temperate species (= southern lineage) are paraphyletic
      groups. The occurrence of R. turanicus in the Mediterranean region is confirmed.
      A consensual re-description of R. sanguineus s.s. and R. turanicus will be
      necessary to solve the taxonomic problems within the so-called R. sanguineus
      group.

PMID- 23880228
TI  - Integrating psychopharmacology and cognitive remediation to treat cognitive
      dysfunction in the psychotic disorders.
AB  - Cognitive deficits are a prominent and enduring aspect of schizophrenia, which
      pose a significant barrier to achieving functional goals. The most promising
      intervention for treating cognitive impairment is cognitive remediation (CR), a
      behaviorally based therapy associated with medium effect sizes for cognitive and
      functional outcomes. However, there is a sizeable group of nonresponders whose CR
      outcomes become limited when the therapeutic approach fails to address individual
      differences in baseline cognition, motivation variables, and the extent to which
      CR offers opportunities for generalization. This speaks to a need to develop
      cognitive interventions that are both personalized and scalable. Emerging data
      suggest that specific pharmacological agents have the potential to enhance and
      accelerate behaviorally based CR effects. This article will review the rationale
      and preliminary evidence to support combining CR and pharmacotherapy. We will
      review crucial aspects of cognitive interventions that offer the most promise for
      improving not only cognitive outcomes, but also for enhancing improvement in real
      world functioning. Finally, we will address methodological issues to be
      considered for future research on combined pharmacological and CR interventions. 

PMID- 23880229
TI  - Staphylococcal cassette chromosome mec characterization of methicillin-resistant
      Staphylococcus aureus strains isolated at the military hospital of
      Constantine/Algeria.
AB  - Staphylococcal cassette chromosome mec is a genetic mobile element that carries
      the gene mecA mediating the methicillin resistance in staphylococci. The aim of
      this study is to type the Staphylococcal cassette chromosome mec (SCCmec) in 64
      non-redundant methicillin-resistant Staphylococcus aureus (MRSA) strains
      recovered at the military hospital of Constantine (Algeria) between 2005 and
      2007. Methicillin resistance was detected by oxacillin and cefoxitin discs and
      PBP2a test, and then confirmed by mecA PCR. The SCCmec complex types were
      determined by real time PCR. The analysis showed that 50 isolates were hospital
      acquired (HA-MRSA) and 14 were community-acquired (CA-MRSA). SCCmec type IV and V
      (traditionally attributed to CA-MRSA) were harbored by both HA-MRSA and CA-MRSA,
      while SCCmec type I, II and III were not recorded. These findings motivate more
      investigations to be carried on HA-MRSA in our hospital and other national health
      care centers. 

PMID- 23880230
TI  - Advanced Parkinson's disease: clinical characteristics and treatment. Part II.
AB  - INTRODUCTION: Many patients who have had Parkinson's disease (PD) for several
      years will present severe motor fluctuations and dyskinesias which require more
      aggressive therapies. The different approaches which are now available include
      deep brain stimulation of the subthalamic nucleus or medial globus pallidus,
      subcutaneous infusion of apomorphine, and intestinal infusion of levodopa
      carbidopa. OBJECTIVE: To define the indications and results for the 3 available
      therapies for advanced PD. DEVELOPMENT: Exhaustive review of the literature
      concerning the indications and results of deep brain stimulation, subcutaneous
      apomorphine infusion and duodenal infusion of levodopa/carbidopa gel to treat
      patients with advanced Parkinson disease. CONCLUSIONS: Although numerous studies
      have confirmed the efficacy of the 3 different therapies in advanced PD, there
      are no comparative studies that would allow us to define the best candidate for
      each technique.

PMID- 23880232
TI  - Proteomic changes induced by effective chemopreventive ratios of n-3:n-6 fatty
      acids and tamoxifen against MNU-induced mammary cancer in the rat.
AB  - We used a proteomic approach to gain insights into the mechanisms of protection
      at the protein level by a high n-3:n-6 ratio in the absence and presence of
      Tamoxifen. Four groups were treated with 1-methyl-1-nitrosourea (MNU) and fed the
      following diets with varied n-3:n-6 ratios; group 1 = 1:1; groups 2 and 3 = 10:1
      and 25:1, respectively; group 4: (25:1) plus Tamoxifen (1 mg/kg diet). The plasma
      from six rats/group was pooled and analyzed with the isobaric tags for relative
      and absolute quantitation method; 148 proteins were identified with 95%
      confidence by ProteinPilot 4.0. In plasma of rats fed 10:1, 25:1 n-3:n-6, and
      25:1 plus Tamoxifen, the number of proteins that met our criteria (P <= 0.05,
      error factor <= 2) were 10, 14, and 19 proteins, respectively. Selected proteins
      were further validated by Western blotting. Compared to 1:1, both 10:1 and 25:1
      diets upregulated vitamin D binding protein, gelsolin, and 14-3-3 sigma, reported
      to have tumor suppressive effects, whereas alpha-1B-glycoprotein, which has been
      reported to be elevated in the serum of breast cancer patients was decreased.
      Compared to 25:1, the 25:1 plus Tamoxifen diet downregulated apolipoprotein E,
      haptoglobin, and inter-alpha-inhibitor H4 heavy chain. Ingenuity pathway analysis
      determined that the trends of specific proteins were related to lipid metabolism
      in the 25:1 n-3:n-6 group, whereas the 25:1 n-3:n-6 plus Tamoxifen group included
      proteins involved in cancer and inflammation. Our results show that several
      proteins were altered in a manner consistent with chemoprevention. Such proteins
      may serve as biomarkers to monitor efficacy of n-3 and Tamoxifen in future
      clinical chemoprevention trials.

PMID- 23880231
TI  - Dietary polyphenols suppress elevated levels of proinflammatory mediators and
      aromatase in the mammary gland of obese mice.
AB  - In postmenopausal women, obesity is a risk factor for the development of hormone
      receptor-positive breast cancer driven by estrogen. After menopause,
      aromatization of androgen precursors in adipose tissue is a major synthetic
      source of estrogen. Recently, in mouse models and women, we identified an obesity
      inflammation-aromatase axis. This obesity-induced inflammation is characterized
      by crown-like structures (CLS) consisting of dead adipocytes encircled by
      macrophages in breast white adipose tissue. CLS occur in association with NF
      kappaB activation, elevated levels of proinflammatory mediators, and increased
      aromatase expression. Saturated fatty acids released from adipocytes have been
      linked to obesity-related white adipose tissue inflammation. Here we found that
      stearic acid, a prototypic saturated fatty acid, stimulated Akt-dependent
      activation of NF-kappaB resulting in increased levels of proinflammatory
      mediators [TNF-alpha, interleukin (IL)-1beta, COX-2] in macrophages leading, in
      turn, to the induction of aromatase. Several polyphenols (resveratrol, curcumin,
      epigallocatechin gallate) blocked these inductive effects of stearic acid.
      Zyflamend, a widely used polyherbal preparation that contains numerous
      polyphenols, possessed similar suppressive effects. In a mouse model of obesity,
      treatment with Zyflamend suppressed levels of phospho-Akt, NF-kappaB binding
      activity, proinflammatory mediators, and aromatase in the mammary gland.
      Collectively, these results suggest that targeting the activation of NF-kappaB is
      a promising approach for reducing levels of proinflammatory mediators and
      aromatase in inflamed mouse mammary tissue. Further investigation in obese women
      is warranted.

PMID- 23880233
TI  - Electromyographic patterns of lower limb muscles during apprehensive gait in
      younger and older female adults.
AB  - OBJECTIVE: Investigate the influence of apprehensive gait on activation and
      cocontraction of lower limb muscles of younger and older female adults. METHODS:
      Data of 17 younger (21.47+/-2.06yr) and 18 older women (65.33+/-3.14yr) were
      considered for this study. Participants walked on the treadmill at two different
      conditions: normal gait and apprehensive gait. The surface electromyographic
      signals (EMG) were recorded during both conditions on: rectus femoris (RF),
      vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), tibialis
      anterior (TA), gastrocnemius lateralis (GL), and soleus (SO). RESULTS:
      Apprehensive gait promoted greater activation of thigh muscles than normal gait
      (F=5.34 and p=0.007, for significant main effect of condition; RF, p=0.002; VM,
      p<0.001; VL, p=0.003; and BF, p=0.001). Older adults had greater cocontraction of
      knee and ankle stabilizer muscles than younger women (F=4.05 and p=0.019, for
      significant main effect of groups; VM/BF, p=0.010; TA/GL, p=0.007; and TA/SO,
      p=0.002). CONCLUSION: Apprehensive gait promoted greater activation of thigh
      muscles and older adults had greater cocontraction of knee and ankle stabilizer
      muscles. Thus, apprehensive gait may leads to increased percentage of
      neuromuscular capacity, which is associated with greater cocontraction and
      contribute to the onset of fatigue and increased risk of falling in older people.

PMID- 23880234
TI  - Effect of aging on properties of motor unit action potentials in the rat medial
      gastrocnemius muscle.
AB  - The purpose of this study was to investigate whether age-related changes in motor
      unit (MU) contractile properties are reflected in parameters of motor unit action
      potentials (MUAPs). MUs of the medial gastrocnemius muscle were functionally
      isolated in anaesthetized Wistar rats. A control group of young animals (5-10mo)
      was compared to two groups of old rats (24-25mo and 28-30mo). The basic
      contractile properties of MUs as well as the amplitude, total duration, peak-to
      peak time, and number of turns within MUAPs were measured. Effects of aging were
      mainly observed for fast fatigable MUs (a prolongation of MUAPs and increased
      number of turns). The MUAP amplitude did not change significantly with aging in
      either MU type, but it correlated to the twitch or tetanic forces, which tended
      to increase with age, especially for slow MUs. We concluded that the prolongation
      of MUAPs and the greater incidence of signal turns was probably a result of a
      decrease in muscle fiber conduction velocity and/or an increase in their
      dispersion, and enlargement of MU territories - presumably caused by axonal
      sprouting of surviving motoneurons. The latter might also be responsible for the
      observed age-related tendency for a increase in MUAP amplitudes in slow MUs. 

PMID- 23880235
TI  - Genomic structure, characterization and expression analysis of a manganese
      superoxide dismutase from pearl oyster Pinctada fucata.
AB  - Manganese superoxide dismutase (MnSOD) is a major component of the cellular
      defense mechanisms against oxidative damage. We cloned and analyzed the
      expression pattern and genomic structure of the MnSOD gene of pearl oyster
      Pinctada fucata, hereafter designated as PoMnSOD. The full-length PoMnSOD cDNA
      was 1080 bp in length and consisted of a 5'-untranslated region (UTR) of 222 bp,
      a 3'-UTR of 318 bp with a polyadenylation signal (AATAAA) at 15 nucleotides
      upstream of the poly (A) tail, and an open reading frame (ORF) of 540 bp encoding
      a polypeptide of 180 amino acids with an estimated molecular mass of 20.4 kDa and
      a predicted pI of 6.72. Sequence analysis showed that PoMnSOD contained MnSOD
      family signatures F(44)NGGGHLNH(52), I(97)QGSGWGWLA(106) and D(138)VWEHAYY(145),
      four conserved residues for manganese metal binding (H(4), H(52), D(138) and
      H(142)), and two potential N-glycosylation sites (N(33) and N(51)). Homology
      analysis revealed that PoMnSOD shared 47.6-55.9% identity and 57.4-65.6%
      similarity to the other known PoMnSOD amino acid sequences. PoMnSOD genomic DNA
      was 5040 bp in length and contained three exons and two introns, which was a
      tripartite organization and coincided with the consensus GT-AG splicing rule.
      PoMnSOD promoter contained the various transcription factors associated with the
      immune modulation and stress responses. Quantitative RT-PCR analysis demonstrated
      that PoMnSOD was constitutively expressed in all detected tissues, and PoMnSOD
      mRNA expression was significantly up-regulated in intestine, mantle, gills,
      digestive gland and haemocytes after Vibrio alginolyticus injection. These
      results suggested that PoMoSOD was an acute-response protein involved in the
      innate immune responses of pearl oyster, and provided general information about
      the mechanisms of innate immune defense against bacterial infection in pearl
      oyster.

PMID- 23880236
TI  - Gestational flu exposure induces changes in neurochemicals, affiliative hormones
      and brainstem inflammation, in addition to autism-like behaviors in mice.
AB  - The prevalence of neurodevelopmental disorders such as autism is increasing,
      however the etiology of these disorders is unclear and thought to involve a
      combination of genetic, environmental and immune factors. A recent
      epidemiological study found that gestational viral exposure during the first
      trimester increases risk of autism in offspring by twofold. In mice gestational
      viral exposures alter behavior of offspring, but the biological mechanisms which
      underpin these behavioral changes are unclear. We hypothesized that gestational
      viral exposure induces changes in affiliative hormones, brainstem autonomic
      nuclei and neurotransmitters which are associated with behavioral alterations in
      offspring. To address this hypothesis, we exposed pregnant mice to influenza A
      virus (H3N2) on gestational day 9 and determined behavioral, hormonal and
      brainstem changes in male and female offspring. We found that gestational flu
      exposure induced dose-dependent alterations in social and aggressive behaviors
      (p<=0.05) in male and female offspring and increases in locomotor behaviors
      particularly in male offspring (p<=0.05). We found that flu exposure was also
      associated with reductions in oxytocin and serotonin (p<=0.05) levels in male and
      female offspring and sex-specific changes in dopamine metabolism. In addition we
      found changes in catecholaminergic and microglia density in brainstem tissues of
      male flu exposed offspring only (p<=0.05). This study demonstrates that
      gestational viral exposure induces behavioral changes in mice, which are
      associated with alterations in affiliative hormones. In addition we found sex
      specific changes in locomotor behavior, which may be associated with sex-specific
      alterations in dopamine metabolism and brainstem inflammation. Further
      investigations into maternal immune responses are necessary to unravel the
      molecular mechanisms which underpin abnormal hormonal, immune and behavioral
      responses in offspring after gestational viral exposure.

PMID- 23880237
TI  - In situ probing the effect of potentials on the microenvironment of heterotrophic
      denitrification biofilm with microelectrodes.
AB  - Bio-electrochemical reactor provides a promising technology to remove nitrogen
      contaminants in water. In this study, a heterotrophic biofilm for denitrification
      process was developed, and stable total nitrogen removal efficiencies (>80%) were
      achieved. Fluorescence in situ hybridization showed that genes norB mainly
      transcribed in inner biofilm while genes nosZ showed similar transcription
      activities in the entire biofilm. The microelectrodes of pH and nitrous oxide
      (N2O) were applied to profile the microenvironment of denitrification biofilm. In
      all measurements, the microenvironment pH decreased as a function of biofilm
      depth. The highest N2O concentration of 90 MUM in biofilm was detected when the
      bulk solution pH was 7.3, and an applied potential of -0.2V did not decrease the
      yield of N2O in biofilm at pH 7.3. Nevertheless, pH 9.5 or an applied potential
      of -0.4V seemed not to suppress the yield of N2O in biofilm.

PMID- 23880238
TI  - Dose and frequency dependent effects of olive mill wastewater treatment on the
      chemical and microbial properties of soil.
AB  - Olive mill wastewater (OMW) is a problematic by-product of olive oil production.
      While its high organic load and polyphenol concentrations are associated with
      troublesome environmental effects, its rich mineral and organic matter contents
      represent valuable nutrients. This study aimed to investigate the valorization of
      this waste biomass as a potential soil conditioner and fertilizer in agriculture.
      OMW was assayed at three doses 50, 100, and 200 m(3) ha(-1) year(-1)) over three
      successive years in olive fields. The effects of the effluent on the physico
      chemical and microbial properties of soil-layers were assessed. The findings
      revealed that the pH of the soil decreased but electrical conductivity and
      organic matter, total nitrogen, sodium, and potassium soil contents increased in
      proportion with OMW concentration and frequency of application. While no
      variations were observed in phosphorus content, slow increases were recorded in
      calcium and magnesium soil contents. Compared to their control soil counterparts,
      aerobic bacteria and fungi increased in proportion with OMW spreading rates. The
      models expressing the correlation between progress parameters and OMW doses were
      fitted into a second degree polynomial model. Principal component analysis showed
      a strong correlation between soil mineral elements and microorganisms. These
      parameters were not related to phosphorus and pH.

PMID- 23880239
TI  - Arsenic(III) and iron(II) co-oxidation by oxygen and hydrogen peroxide: divergent
      reactions in the presence of organic ligands.
AB  - Iron-catalyzed oxidation of As(III) to As(V) can be highly effective for toxic
      arsenic removal via Fenton reaction and Fe(II) oxygenation. However, the
      contribution of ubiquitous organic ligands is poorly understood, despite its
      significant role in redox chemistry of arsenic in natural and engineered systems.
      In this work, selected naturally occurring organic ligands and synthetic ligands
      in co-oxidation of Fe(II) and As(III) were examined as a function of pH, Fe(II),
      H2O2, and radical scavengers (methanol and 2-propanol) concentration. As(III) was
      not measurably oxidised in the presence of excess ethylenediaminetetraacetic acid
      (EDTA) (i.e. Fe(II):EDTA<1:1), contrasting with the rapid oxidation of Fe(II) by
      O2 and H2O2 at neutral pH under the same conditions. However, partial oxidation
      of As(III) was observed at a 2:1 ratio of Fe(II):EDTA. Rapid Fe(II) oxidation in
      the presence of organic ligands did not necessarily result in the coupled As(III)
      oxidation. Organic ligands act as both iron speciation regulators and radicals
      scavengers. Further quenching experiments suggested both hydroxyl radicals and
      high-valent Fe species contributed to As(III) oxidation. The present findings are
      significant for the better understanding of aquatic redox chemistry of iron and
      arsenic in the environment and for optimization of iron-catalyzed arsenic
      remediation technology. 

PMID- 23880240
TI  - Heavy metal pollution status in surface sediments of Swan Lake lagoon and
      Rongcheng Bay in the northern Yellow Sea.
AB  - The national 'Shandong Peninsula Blue Economic Zone Development Plan' compels the
      further understanding of the distribution and potential risk of metals pollution
      in the east coast of China, where the rapid economic and urban development have
      been taken off and metal pollution has become a noticeable problem. Surface
      sediments collected from the largest swan habitat in Asia, the Swan Lake lagoon
      and the surrounding coastal area in Rongcheng Bay in northern Yellow Sea, were
      analyzed for the total metal concentrations and chemical phase partitioning of
      five heavy metals (Cu, Zn, Pb, Cd, and Cr). Metal contents in the studied region
      have increased significantly in the past decade. The speciation analyzed by the
      sequential extraction showed that Zn and Cr were present dominantly in the
      residual fraction and thus of low bioavailability, while Cd, Pb and Cu were found
      mostly in the non-residual fraction thus of high potential availability,
      indicating significant anthropogenic sources. Among the five metals, Cd is the
      most outstanding pollutant and presents high risk, and half of the surface
      sediments in the studied region had a 21% probability of toxicity based on the
      mean Effect Range-Median Quotient. At some stations with comparable total metal
      contents, remarkably different non-residual fraction portions were determined,
      pointing out that site-specific risk assessment integrating speciation is crucial
      for better management practices of coastal sediments. 

PMID- 23880241
TI  - Survival and behavior of the insecticide-exposed predators Podisus nigrispinus
      and Supputius cincticeps (Heteroptera: Pentatomidae).
AB  - Pentatomid stinkbugs are important predators of defoliating caterpillars in
      agricultural and forestry systems, and knowledge of the impact of insecticides on
      natural enemies is important information for integrated pest management (IPM)
      programs. Thus, we assessed the toxicity and behavioral sublethal response of the
      predators Podisus nigrispinus and Supputius cincticeps exposed to deltamethrin,
      methamidophos, spinosad and chlorantraniliprole, insecticides commonly used to
      control the velvetbean caterpillar (Anticarsia gemmatalis) in soybean crops. With
      the exception of deltamethrin for S. cincticeps, all insecticides showed higher
      acute toxicity to the prey than to these natural enemies providing effective
      control of A. gemmatalis. The recommended field concentration of deltamethrin,
      methamidophos and spinosad for controlling A. gemmatalis caused 100% mortality of
      P. nigrispinus and S. cincticeps nymphs. Chlorantraniliprole was the less toxic
      and the most selective insecticide to these predators resulting in mortalities of
      less than 10% when exposed to 10* the recommended field concentration for a
      period of 72 h. Behavioral pattern changes in predators were found for all
      insecticides, especially methamidophos and spinosad, which exhibited irritability
      (i.e., avoidance after contact) to both predator species. However, insecticide
      repellence (i.e., avoidance without contact) was not observed in any of the
      insects tested. The lethal and sublethal effects of pesticides on natural enemies
      is of great importance for IPM, and our results indicate that substitution of
      pyrethroid and organophosphate insecticides at their field rates by
      chlorantraniliprole may be a key factor for the success of IPM programs of A.
      gemmatalis in soybeans.

PMID- 23880242
TI  - Distribution and ecological risk of organochlorine pesticides and polychlorinated
      biphenyls in sediments from the Mediterranean coastal environment of Egypt.
AB  - Organochlorine contamination in the Mediterranean coastal environment of Egypt
      was assessed based on 26 surface sediments samples collected from several
      locations on the Egyptian coast, including harbors, coastal lakes, bays, and
      estuaries. The distribution and potential ecological risk of contaminants is
      described. Organochlorine compounds (OCs) were widely distributed in the coastal
      environment of Egypt. Concentrations of PCBs, DDTs, and chloropyrifos ranged from
      0.29 to 377ngg(-1) dw, 0.07 to 81.5ngg(-1) dw, and below the detection limit (DL)
      to 288ngg(-1) dw, respectively. Other organochlorinated pesticides (OCP) studied
      were 1-2 orders of magnitude lower. OCP and PCBs had higher concentrations at
      Burullus Lake, Abu Qir Bay, Alexandria Eastern Harbor, and El Max Bay compared to
      other sites. OCP and PCB contamination is higher in the vicinity of possible
      input sources such as shipping, industrial activities and urban areas. PCB
      congener profiles indicated they were derived from more than one commercially
      available mixture. The ratios of commercial chlordane and heptachlor metabolites
      indicate historical usage; however, DDT and HCHs inputs at several locations
      appear to be from recent usage. The concentrations of PCBs and DDTs are similar
      to those observed in sediments from coastal areas of the Mediterranean Sea.
      Ecotoxicological risk from DDTs and PCBs is greatest in Abu Qir Bay, Alexandria
      Harbor, and El-Max Bay.

PMID- 23880243
TI  - Survival of Helicobacter suis bacteria in retail pig meat.
AB  - Helicobacter (H.) suis colonizes the gastric mucosa of pigs world-wide and is the
      most prevalent non-Helicobacter pylori Helicobacter species in humans. This agent
      might be transmitted to humans by manipulation or consumption of contaminated
      pork. H. suis is a very fastidious micro-organism and is extremely difficult to
      isolate. Therefore, we developed a non-culture dependent, quantitative detection
      method allowing differentiation of viable from dead H. suis bacteria in pork.
      This was established by a combination of ethidium bromide monoazide (EMA)
      treatment and real-time (RT)-PCR. This EMA RT-PCR was applied to 50 retail pork
      samples. In two samples, viable H. suis bacteria were detected. Sequence analysis
      of the obtained PCR products confirmed the presence of H. suis DNA. Viable H.
      suis bacteria persisted for at least 48h in experimentally contaminated pork. In
      conclusion, consumption of contaminated pork may constitute a new route of
      transmission for H. suis infections in humans. 

PMID- 23880244
TI  - Community dynamics of coagulase-negative staphylococci during spontaneous artisan
      type meat fermentations differ between smoking and moulding treatments.
AB  - Coagulase-negative staphylococci (CNS) that are naturally present in the raw meat
      batter of fermented sausages or that originate from the addition of a starter
      culture play a role in flavour development. A wide species diversity of CNS can
      be present in fermented meats, but it is not fully clear yet how specific process
      parameters select for specific CNS by affecting their community dynamics.
      Therefore, the influence of smoking and moulding treatments on the CNS community
      dynamics in spontaneously fermented, artisan-type sausages was investigated.
      During the fermentation stage, the meat batter was in all cases dominated by
      Staphylococcus saprophyticus, in addition to Lactobacillus sakei as governing
      lactic acid bacterium. Following fermentation, the bacterial communities were not
      perturbed by the smoking treatment, since both L. sakei and S. saprophyticus
      remained dominant throughout the ripening stage and prevailed in the end
      products. Yet, when fermentation was followed by a moulding step with Penicillium
      nalgiovense, a shift of the CNS communities towards dominance by Staphyloccocus
      equorum was seen, despite a similar evolution of L. sakei. This effect was
      possibly due to a pH rise caused by the mould, a hypothesis which was reinforced
      by the finding that the isolated strain S. equorum DBX-S-17 was more sensitive to
      low pH than the isolated strain S. saprophyticus DFL-S-12 during growth
      experiments in brain heart infusion (BHI). Differences in CNS communities may
      affect sausage flavour, due to intraspecies variations in metabolic conversions
      of, for instance, amino acids. The fact that 3-methyl-butanal was only found in
      the moulded sausage, which was dominated by S. equorum, may be related to the
      finding that the isolated strain of this species was able to produce this
      compound in BHI medium, whereas the isolated strain of S. saprophyticus was not. 

PMID- 23880245
TI  - Association of cytomegalovirus and other pathogens with frailty and diabetes
      mellitus, but not with cardiovascular disease and mortality in psycho-geriatric
      patients; a prospective cohort study.
AB  - BACKGROUND: Studies about associations of infections with herpes viruses and
      other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP)
      with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or
      mortality are conflicting. Since high levels of antibodies against these
      pathogens occur in the elderly, the role of these pathogens in morbidity and
      mortality of vulnerable elderly was explored. RESULTS: Blood samples of 295
      community dwelling psycho-geriatric patients were tested for IgG antibodies to
      herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus
      (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP.
      Frailty was defined with an easy-to-use previously described frailty risk score.
      Relative risks (RR) with 95% confidence intervals were calculated to evaluate
      associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for
      subsequent mortality were tested using Kaplan Meier analyses and Cox proportional
      hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as
      frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated
      with frailty, as shown by using both qualitative and quantitative tests, RR ratio
      1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High
      IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95%
      CI: 1.57-6.49). None of the single or combined pathogens were significantly
      associated with mortality and/or CVD. CONCLUSIONS: Prior CMV infection is
      associated with frailty, which could be in line with the concept that CMV might
      have an important role in immunosenescence, while high IgG titers of HHV6 and EBV
      are associated with DM. No association between a high pathogen burden and
      morbidity and/or mortality could be demonstrated.

PMID- 23880246
TI  - Heavy drinking during periods of high unemployment: 15-year trend study of the
      role of race/ethnicity.
AB  - OBJECTIVES: This study conceptualized high unemployment rate as a stressor
      deriving from the social structure. It tracked American adults' heavy drinking
      rates 1997-2011, intending to examine (1) whether heavy drinking escalates with
      rising unemployment, and (2) whether racial minorities, who feel economic
      downturns more than the majority, engage in heavy drinking at a higher level than
      Whites in times of high unemployment. METHODS: Research questions were answered
      using data from the Combined National Health Interview Survey. The present final
      sample included only respondents classified as heavy drinkers: those reporting
      that, on days (in the preceding year) on which they had consumed alcohol, they
      had regularly had at least 5 drinks. RESULTS: The study, which considered
      individual-level social structural factors, overall found rising unemployment
      rate to be associated with high measures for heavy-drinking frequency but low
      measures for heavy-drinking quantity. It did not find race to moderate the
      unemployment-heavy-drinking relationship, although some empirical evidence has
      shown racial minorities to be relatively more responsive to fluctuating
      unemployment inherent in the economic cycle. CONCLUSIONS: Our results in general
      call for further research on roles of gender and race in heavy drinking,
      especially where Black females are concerned. Blacks' greater heavy-drinking
      frequency and greater heavy-drinking quantity (versus Whites) observed in this
      study may shed light on persistent racial disparities in Americans' health.

PMID- 23880247
TI  - Heart rate correlates of utilitarian moral decision-making in alcoholism.
AB  - BACKGROUND: Recent studies of moral reasoning in patients with alcohol use
      disorders have indicated a 'utilitarian' bias, whereby patients are more likely
      to endorse emotionally aversive actions in favor of aggregate welfare (e.g., to
      kill a person in order to save a group of people). The aim of the present study
      was to examine psychophysiological correlates of this tendency indexed by heart
      rate. METHODS: The sample was composed by 31 alcohol-dependent individuals and 34
      healthy controls without alcohol use disorders. Electrocardiogram was recorded at
      rest and during execution of a validated moral judgment task, including non-moral
      scenarios, and moral dilemmas that were either high in emotional salience
      ("personal scenarios") or low in emotional salience ("impersonal scenarios").
      RESULTS: Alcohol-dependent individuals showed a blunted response to moral
      dilemmas. Furthermore, healthy controls displayed decreased heart rate to the
      personal vs. impersonal or non-moral scenarios, while alcohol-dependent
      individuals failed to differentiate dilemmas in terms of heart rate both prior
      decision-making and its post appraisal. These deficits were not related to
      baseline differences in Heart Rate. CONCLUSION: Our findings indicate that
      alcohol-dependent individuals failed to engage emotional aversive reactions to
      personal moral violations in terms of heart rate response.

PMID- 23880248
TI  - Antiretroviral therapy for prevention of HIV transmission: potential role for
      people who inject drugs in Central Asia.
AB  - Interest in the use of antiretroviral therapy (ART) for prevention stems from
      mounting evidence from research studies demonstrating that ART is associated with
      a decrease in sexual HIV transmission among serodiscordant couples and, perhaps,
      in other populations at risk. There is paucity of data on the efficacy of ART for
      prevention in key populations, including persons who inject drugs (PWID). In this
      paper, we examine the current status of HIV services for PWID in Central Asia,
      the use of ART by this population and explore ART for prevention for PWID in this
      context. We also discuss research and implementation questions with relevance to
      such a strategy in the region. 

PMID- 23880250
TI  - [Communicating about breastfeeding in a child and family-centered care approach].
AB  - Breastfeeding is a public health issue: health expenditures related to not
      breastfeeding have been evaluated in the US and the UK, annually amounting to
      billions of dollars and tens of millions of pounds. Breastfeeding is also a
      family issue, and this intimate practice involves the presence of emotions and
      feelings going beyond rationality. Healthcare professionals are responsible for
      promoting health in the physical, mental, and social domains. Information and
      individualized support are essential to enable parents to make the best possible
      choice and play an active role in their own health and that of their child. There
      are communication and support tools to help build a trusting relationship between
      professionals and parents, to provide relevant information, and to assist parents
      in their reflection, while supporting them in their choices. In France,
      healthcare professionals have available a tool for intervention and education
      proposed by the French Institute for Health Promotion and Health Education
      (Institut national de prevention et d'education pour la sante, INPES) in the
      Pregnancy and Parenting section. It provides a high degree of homogeneity in the
      various healthcare professional's interventions occurring during pregnancy and
      thereafter. It aims to promote and strengthen parenting skills. Thus, support for
      breastfeeding is part of a dynamic process to support parenting, focused on
      people, not on the object, for both ethical and effectiveness reasons. 

PMID- 23880249
TI  - The clinical course of alcohol use disorders: using joinpoint analysis to aid in
      interpretation of growth mixture models.
AB  - BACKGROUND: The clinical course of alcohol use disorders (AUD) is marked by great
      heterogeneity both within and between individuals. One approach to modeling this
      heterogeneity is latent growth mixture modeling (LGMM), which identifies a number
      of latent subgroups of drinkers with drinking trajectories that are similar
      within a latent subgroup but different between subgroups. LGMM is data-driven and
      uses an iterative process of testing a sequential number researcher-selected of
      latent subgroups then selecting the best fitting model. Despite the advantages of
      LGMM (e.g., identifying subgroups among heterogeneous longitudinal data), one
      limitation is the lack of precision of LGMM to model abrupt changes in drinking
      during treatment that are often observed by clinicians. Joinpoint analysis (JPA)
      is a data analysis procedure that is used to identify discrete change points in
      longitudinal data (e.g., changes from increasing to decreasing or decreasing to
      increasing). METHOD: This study presents a demonstration of using JPA as a post
      hoc procedure for LGMM to improve accuracy in modeling abrupt changes in clinical
      course of AUD. RESULTS: Results from this secondary data analysis of 549 AUD
      participants participating in the NIAAA sponsored relapse replication and
      extension project uncovered four latent classes of drinking trajectories.
      DISCUSSION: Within these trajectories the addition of JPA improved precision in
      modeling the clinical course of AUDs.

PMID- 23880251
TI  - [Memory boxes in the neonatal period: caregivers' opinions after 1 year of
      practice].
AB  - Perinatal death is a profound experience for childbearing families and mementoes
      are key to providing essential records of the baby's life and death. The aim of
      this observational study was to evaluate the caregiver's feelings on 1 year of
      using memory boxes in the neonatal and pediatric intensive care unit of a
      tertiary care center. METHOD: Anonymous survey containing 14 questions. RESULTS:
      During the study period, a memory box was made for 31 neonates (24 preterm and 7
      term infants) and 4 infants. Thirty-nine (54%; 32/62 nurses; 7/12 physicians)
      answers were obtained. Caregivers considered that memory boxes: i) were
      appropriate for death in the neonatal period (80-92%) or for infants who had
      never returned home (80%), ii) helped parents in their grieving process (77%),
      and iii) helped caregivers to support parents respecting their spirituality and
      emotional needs (62%). Some restrictions were mentioned such as the symbolic
      impact of the box mimicking a coffin and the modeling clay used for footprints
      recalling children's toys (10%) and the possibility of hurting parents in their
      religious convictions (18%) or feelings (20%). For the majority of the
      caregivers, memory boxes were considered helpful for families (82%); a few
      thought they were helpful for the ICU team (26%). CONCLUSIONS: This is the first
      study describing caregivers' opinions about the memory box practices. Memory
      boxes are considered helpful for bereaved parents, especially in the neonatal
      period, but are of little help to the caregivers.

PMID- 23880252
TI  - [Neonatal exposure to anesthesia and adverse cognitive outcome in childhood.
      Insight from epidemiology].
AB  - Adverse effects of general anesthesia have been observed repeatedly, mainly in
      animal model studies and in rodents. Already in 2005, the Food and Drug
      Administration recommended proceeding to similar studies in human infants,
      highlighting that there were several methodological issues to solve before being
      able to appreciate the risk of anesthetic agents on the developing brain. Most
      studies conducted in humans were observational studies, showing a very mild
      adverse effect on cognitive functions, an effect that disappeared when properly
      adjusted analysis was performed (with various modalities for analysis and
      protocols for these adjusted results). Due to numerous biases in these
      observational studies - bias related to selection of the population and the
      control subjects and their comparability as well as outcome measure assessment,
      it has become extremely important to conduct prospective studies. Two
      international studies are currently under way, but their results will not be
      available for a few years. How animal model results can be relevant to human
      babies remains controversial. Until today, and according to the current state of
      the art, no changes in practices are indicated, and it is important for infants
      and their families to avoid sensationalist messages. 

PMID- 23880253
TI  - Spatial pattern of schistosomiasis in Xingzi, Jiangxi Province, China: the
      effects of environmental factors.
AB  - BACKGROUND: The recent rebounds of schistosomiasis in the middle and lower
      reaches of the Yangtze River pose a challenge to the current control strategies.
      In this study, identification of potential high risk snail habitats was proposed,
      as an alternative sustainable control strategy, in Xingzi County, China.
      Parasitological data from standardized surveys were available for 36,208 locals
      (aged between 6-65 years) from 42 sample villages across the county and used in
      combination with environmental data to investigate the spatial pattern of
      schistosomiasis risks. METHODS: Environmental factors measured at village level
      were examined as possible risk factors by fitting a logistic regression model to
      schsitosomiasis risk. The approach of ordinary kriging was then used to predict
      the prevalence of schistosomiasis over the whole county. RESULTS: Risk analysis
      indicated that distance to snail habitat and wetland, rainfall, land surface
      temperature, hours of daylight, and vegetation are significantly associated with
      infection and the residual spatial pattern of infection showed no spatial
      correlation. The predictive map illustrated that high risk regions were located
      close to Beng Lake, Liaohuachi Lake, and Shixia Lake. CONCLUSIONS: Those
      significant environmental factors can perfectly explain spatial variation in
      infection and the high risk snail habitats delineated by the predicted map of
      schistosomiasis risks will help local decision-makers to develop a more
      sustainable control strategy.

PMID- 23880254
TI  - Effects of abdominal binding on field-based exercise responses in Paralympic
      athletes with cervical spinal cord injury.
AB  - Abdominal binding has been shown to improve resting cardiorespiratory function in
      individuals with cervical SCI, but it is not yet clear whether this approach
      improves the exercise response. OBJECTIVES: To determine the effects of abdominal
      binding on parameters relating to wheelchair sports performance in highly-trained
      athletes with cervical SCI. DESIGN: Repeated-measures field-based study. METHODS:
      Ten Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) completed
      a series of exercise tests in two conditions (bound and unbound). The following
      parameters were assessed: agility and acceleration/deceleration performance;
      cardiorespiratory function and gross efficiency during submaximal wheelchair
      propulsion; anaerobic performance and propulsion kinematics during a 30s Wingate
      test; repeated sprint performance during a 10*20m test; and aerobic performance
      during a repeated 4min push test. RESULTS: Compared to unbound, 6 of 17 field
      based performance measures changed significantly with binding. Time to complete
      the acceleration/deceleration test decreased (p=0.005), whereas distances covered
      during the repeated 4min push test increased (p<0.043). Binding elicited
      significant reductions in minute ventilation during submaximal wheelchair
      propulsion (p=0.040) as well as blood lactate accumulation and limb discomfort
      during the second set of the repeated 4min push test (p=0.012 and 0.022). There
      were no statistically significant effects of binding on any other variable.
      CONCLUSIONS: Abdominal binding improves some important measures of field-based
      performance in highly-trained athletes with cervical SCI. The changes may be
      attributable, at least in part, to improvements in trunk stability, ventilatory
      efficiency and/or haemodynamics.

PMID- 23880256
TI  - Windowed R-PDLF recoupling: a flexible and reliable tool to characterize
      molecular dynamics.
AB  - This work focuses on the improvement of the R-PDLF heteronuclear recoupling
      scheme, a method that allows quantification of molecular dynamics up to the
      microsecond timescale in heterogeneous materials. We show how the stability of
      the sequence towards rf-imperfections, one of the main sources of error of this
      technique, can be improved by the insertion of windows without irradiation into
      the basic elements of the symmetry-based recoupling sequence. The impact of this
      modification on the overall performance of the sequence in terms of scaling
      factor and homonuclear decoupling efficiency is evaluated. This study indicates
      the experimental conditions for which precise and reliable measurement of dipolar
      couplings can be obtained using the popular R18(1)(7) recoupling sequence, as
      well as alternative symmetry-based R sequences suited for fast MAS conditions. An
      analytical expression for the recoupled dipolar modulation has been derived that
      applies to a whole class of sequences with similar recoupling properties as
      R18(1)(7). This analytical expression provides an efficient and precise way to
      extract dipolar couplings from the experimental dipolar modulation curves. We
      hereby provide helpful tools and information for tailoring R-PDLF recoupling
      schemes to specific sample properties and hardware capabilities. This approach is
      particularly well suited for the study of materials with strong and heterogeneous
      molecular dynamics where a precise measurement of dipolar couplings is crucial.

PMID- 23880255
TI  - Development of memory for spatial locations and object/place associations in
      infant rhesus macaques with and without neonatal hippocampal lesions.
AB  - This study traces the development of spatial memory abilities in monkeys and
      reports the effects of selective neonatal hippocampal lesions on performance
      across development. Two different versions of the visual paired-comparison (VPC)
      task were used. The VPC-Spatial-Location task tested memory for object-locations
      that could be solved using an egocentric spatial frame of reference and the VPC
      Object-In-Place task taxed memory for spatial relations using an allocentric
      reference frame. Eleven rhesus macaques (6 neonatal sham-operated controls and 5
      with neonatal neurotoxic hippocampal lesions) were tested on both tasks as
      infants (8 months), juveniles (18 months), and adults (5-6 years). Memory for
      spatial locations was present by 18 months of age, whereas memory for object
      place relations was present only in adulthood. Also, neonatal hippocampal lesions
      delayed the emergence of memory for spatial locations and abolished memory for
      object-place associations, particularly in animals that had sustained extensive
      and bilateral hippocampal lesions. The differential developmental time course of
      spatial memory functions and of the effects of neonatal hippocampal lesions on
      these functions are discussed in relation to morphological maturation of the
      medial temporal lobe structures in monkeys. Implications of the findings for the
      neural basis of spatial memory development in humans are also considered.

PMID- 23880257
TI  - [Combined treatment: regimens, indications and safety profile].
AB  - Statins are the current basis of lipid-lowering therapy, despite which may have
      limitations on efficacy and safety. In high risk patients who do not achieve
      current lipid goals, in those intolerant to statins or those with atherogenic
      dyslipidemia, it is possible combine two or more lipid lowering drugs, including
      statins, ezetimibe, bile acid sequestrants, fibrates, niacin and prescription
      omega-3 fatty acids. However, for most of these combination therapies pivotal
      data on clinical outcomes are still lacking. 

PMID- 23880258
TI  - One-visit versus two-visit root canal treatment: effectiveness in the removal of
      endotoxins and cultivable bacteria.
AB  - INTRODUCTION: This clinical study was conducted to compare the effectiveness of 1
      visit versus 2-visit root canal treatment in removing endotoxins and cultivable
      bacteria from primarily infected root canals. METHODS: Forty-eight primarily
      infected root canals were selected and randomly divided into 4 groups: G1, 1%
      NaOCl; G2, 2% chlorhexidine (CHX) gel; G3, 1% NaOCl + Ca(OH)2; and G4, 2% CHX gel
      + Ca(OH)2 (all, n = 12). G1 and G2 involved 1-visit treatment, whereas G3 and G4
      involved 2-visit treatment with the placement of Ca(OH)2 medication for 14 days.
      Samples were collected before and after root canal procedures. A chromogenic LAL
      assay test was used to quantify endotoxins. Culture techniques were used to
      determine bacterial counts. RESULTS: Endotoxins and cultivable bacteria were
      detected in 100% of the initial samples. All treatment protocols were effective
      in reducing bacterial load from infected root canals: G1 (1% NaOCl, 99.97%), G2
      (2% CHX gel, 99.75%), G3 (1% NaOCl + Ca(OH)2, 99.90%), and G4 (2% CHX gel +
      Ca(OH)2, 96.81%), respectively (P < .05). No differences were found in bacterial
      load reduction when comparing 1-visit and 2-visit treatment groups, irrespective
      of the irrigant tested (P > .05). Higher median percentage values of endotoxin
      reduction were achieved in the 2-visit treatment groups (G3, 98.01% and G4,
      96.81%) compared with 1-visit treatment groups (G1, 86.33% and G2, 84.77%) (all P
      < .05). CONCLUSIONS: Both 1-visit and 2-visit root canal treatment protocols were
      effective in reducing bacteria and endotoxins, but they were not able to
      eliminate them in all root canals analyzed. Furthermore, 2-visit root canal
      treatment protocols were more effective in reducing endotoxins than 1-visit root
      canal treatment protocols.

PMID- 23880259
TI  - Predictive values of thermal and electrical dental pulp tests: a clinical study.
AB  - INTRODUCTION: For a diagnostic test to be useful, it is necessary to determine
      the probability that the test will provide the correct diagnosis. Therefore, it
      is necessary to calculate the predictive value of diagnostics. The aim of the
      present study was to identify the sensitivity, specificity, positive and negative
      predictive values, accuracy, and reproducibility of thermal and electrical tests
      of pulp sensitivity. METHODS: The thermal tests studied were the 1, 1, 1, 2
      tetrafluoroethane (cold) and hot gutta-percha (hot) tests. For the electrical
      test, the Analytic Technology Pulp Tester (Analytic Technology, Redmond, WA) was
      used. A total of 110 teeth were tested: 60 teeth with vital pulp and 50 teeth
      with necrotic pulps (disease prevalence of 45%). The ideal standard was
      established by direct pulp inspection. RESULTS: The sensitivities of the
      diagnostic tests were 0.88 for the cold test, 0.86 for the heat test, and 0.76
      for the electrical test, and the specificity was 1.0 for all 3 tests. The
      negative predictive value was 0.90 for the cold test, 0.89 for the heat test, and
      0.83 for the electrical test, and the positive predictive value was 1.0 for all 3
      tests. The highest accuracy (0.94) and reproducibility (0.88) were observed for
      the cold test. CONCLUSIONS: The cold test was the most accurate method for
      diagnostic testing.

PMID- 23880260
TI  - Is a volume of 3.6 mL better than 1.8 mL for inferior alveolar nerve blocks in
      patients with symptomatic irreversible pulpitis?
AB  - INTRODUCTION: The purpose of this retrospective study was to determine the
      success of the inferior alveolar nerve (IAN) block using either 3.6 mL or 1.8 mL
      2% lidocaine with 1:100,000 epinephrine in patients presenting with symptomatic
      irreversible pulpitis. METHODS: As part of 7 previously published studies, 319
      emergency patients presenting with symptomatic irreversible pulpitis received
      either a 1.8-mL volume or 3.6-mL volume of 2% lidocaine with 1:100,000
      epinephrine in an IAN block. One hundred ninety patients received a 1.8-mL
      volume, and 129 received a 3.6-mL volume. Endodontic emergency treatment was
      completed on each subject. Success was defined as the ability to access and
      instrument the tooth without pain (visual analog scale score of 0) or mild pain
      (VAS rating <=54 mm). RESULTS: Success of the 1.8-mL volume was 28%, and for the
      3.6-mL volume it was 39%. There was no statistically significant difference
      between the 2 volumes. CONCLUSIONS: In conclusion, for patients presenting with
      irreversible pulpitis, success was not significantly different between a 3.6-mL
      volume and a 1.8-mL volume of 2% lidocaine with 1:100,000 epinephrine. The
      success rates (28%-39%) with either volume were not high enough to ensure
      complete pulpal anesthesia.

PMID- 23880261
TI  - A micro-computed tomographic analysis of wall thickness of C-shaped canals in
      mandibular first premolars.
AB  - INTRODUCTION: The purpose of this study was to quantitatively evaluate the wall
      thickness of C-shaped canals in mandibular first premolars using micro-computed
      tomographic imaging. The focus was on the relation between the radicular groove
      and the mesial canal wall thickness. METHODS: A total of 148 mandibular first
      premolars were scanned by a micro-computed tomographic scanner. After 3
      dimensional reconstruction of the teeth, 29 specimens were identified to contain
      a C-shaped canal, and then they were analyzed in software Mimics 10.01
      (Materialise, Leuven, Belgium). The buccal and lingual canal wall thickness,
      minimum mesial and distal wall thickness, and the depth and angle of radicular
      grooves were measured at different root levels. Two-way analyses of variance and
      the post hoc Tukey's honestly significant difference test were used to compare
      the groups in relation to canal wall thickness. RESULTS: The buccal and lingual
      canal walls were significantly (P < .005) thicker than the mesial and distal
      walls. The minimum thickness of the mesial walls was significantly (P < .005)
      lower than that of the distal walls, and the locations were frequently at lingual
      sites, with an incidence of 67.3% for the mesial walls and 69.2% for the distal
      walls. Backward multivariate analysis showed that the root level and groove angle
      contributed significantly (P < .005) to the minimum mesial wall thickness.
      CONCLUSIONS: The mesial walls of C-shaped canals in mandibular first premolars
      are the thinnest zones. The minimum mesial wall thickness decreases with the
      increased severity of the radicular groove, and it mainly occurs at lingual
      sites. Care should be taken to avoid perforation at danger zones during shaping
      and post space preparation procedures.

PMID- 23880262
TI  - Histologic examination of condensing osteitis in cadaver specimens.
AB  - OBJECTIVES: Condensing osteitis is a radiographic finding, but with no reported
      histologic investigations in humans. The objectives of this study were to
      evaluate and describe histologically condensing osteitis in human cadaver jaws.
      Patterns of bone formation and presence/absence and nature of inflammation were
      examined. METHODS: Specimens of mandibles and maxillas were obtained from
      cadavers and examined radiographically. Those periapical areas with
      characteristics of condensing osteitis were removed en bloc, decalcified, and
      processed for light microscopy. For comparison, specimens that showed normal
      apical radiographic anatomy were also removed for examination. RESULTS: Normal
      apical regions showed an intact periodontal ligament and a thin layer of alveolar
      bone proper surrounded by cancellous bone with fatty marrow. In contrast, areas
      of condensing osteitis exhibited areas of inflammation or no inflammation,
      occupied by connective tissue. This area was bordered by a rim of varying widths
      of dense lamellar-type bone replacing the cancellous bone and marrow.
      CONCLUSIONS: The histologic changes of condensing osteitis consisted of the
      replacement of cancellous bone with compact bone. Areas of fibrosis and an
      inflammatory infiltrate were seen in some but not all specimens. All teeth
      exhibiting condensing osteitis had an identifiable etiology that likely resulted
      in degenerative pulp disease.

PMID- 23880263
TI  - The effect of dentin on the pulp tissue dissolution capacity of sodium
      hypochlorite and calcium hydroxide.
AB  - INTRODUCTION: Sodium hypochlorite (NaOCl) and calcium hydroxide (Ca[OH]2) have
      tissue dissolution capacity. The aim of this study was to evaluate the potential
      effect of dentin on their tissue dissolution capacity in a novel dentin model.
      METHODS: Dentin models were prepared from 25 freshly extracted human molar teeth;
      the crowns were separated from the roots, and a rectangular inner shape was
      prepared. Pulp tissue samples adjusted to similar weights of 6.5 +/- 0.2 mg were
      randomly divided into 6 groups: NaOCl groups in test tubes or dentin models for 1
      hour, Ca(OH)2 groups in test tubes or dentin models for 1 week, and control
      groups saline in test tubes or dentin models for 1 week. The final weights after
      the experimental period were checked and compared with the initial weights. The
      differences were statistically analyzed. RESULTS: The tissue dissolution capacity
      of Ca(OH)2 was affected by the presence of dentin. Similarly, NaOCl lost its
      effect on the pulp tissue after incubation in dentin. Comparison between all test
      groups showed highly significant differences (P < .001). CONCLUSIONS: Dentin has
      a detrimental effect on the ability of NaOCl and Ca(OH)2 to dissolve pulp tissue.
      The dentin model appears to be an efficient tool for the study of interactions
      between local endodontic medicaments, dentin, and pulp tissue.

PMID- 23880264
TI  - The expression of macrophage migration inhibitory factor is correlated with
      receptor activator of nuclear factor kappa B ligand in induced rat periapical
      lesions.
AB  - INTRODUCTION: Macrophage migration inhibitory factor (MIF) has been defined as a
      key cytokine in regulation of innate and adaptive immunity. The purpose of this
      study was to investigate the immunohistochemical localization of MIF and its
      relationship with receptor activator of nuclear factor kappa B ligand (RANKL)
      protein during the development of periapical lesions in rats. METHODS: Apical
      periodontitis was induced in Wistar rats by occlusal pulp exposure in mandibular
      first molar teeth. The animals were randomly killed at 0, 7, 14, 21, 28, and 35
      days after pulp exposure. The jaws that contained the first molar were obtained
      and were prepared for histologic analysis, enzyme histochemistry,
      immunohistochemistry, and double immunofluorescence staining. RESULTS: From day 0
      to day 35, the areas of periapical bone loss increased and seemed to be
      stabilized on day 35. A few MIF-positive and RANKL-positive cells and osteoclasts
      could be observed on day 7, and all climaxed on day 14. From day 21 to day 35,
      the expression of MIF and RANKL protein decreased, and fewer osteoclasts could be
      observed. CONCLUSIONS: These findings showed that MIF might be associated with
      the differentiation of osteoclasts in the periapical lesions. MIF contributes to
      the pathogenesis of the periapical lesions through the induction of RANKL
      protein.

PMID- 23880265
TI  - Immunoexpression of interleukin 17, transforming growth factor beta1, and
      forkhead box P3 in periapical granulomas, radicular cysts, and residual radicular
      cysts.
AB  - INTRODUCTION: Different cell types and cytokines have been identified as
      contributors to the formation of periapical lesions. In this perspective, this
      study aimed to evaluate the immunoexpression of interleukin (IL)-17, transforming
      growth factor (TGF)-beta1, and the forkhead box P3 (FoxP3) in periapical lesions,
      correlating them with the type of lesion, the intensity of the inflammatory
      infiltrate, and the thickness of the cystic epithelial lining. METHODS: Twenty
      periapical granulomas (PGs), 20 radicular cysts (RCs), and 20 residual radicular
      cysts (RRCs) were submitted to immunohistochemical analysis using anti-IL-17,
      anti-TGF-beta1, and anti-FoxP3 antibodies. RESULTS: In comparison with PGs and
      RCs, RRCs exhibited a lower immunoexpression of IL-17 and TGF-beta1 (P = .021 and
      P < .001, respectively). The number of FoxP3+ cells increased in this order:
      RRCs, RCs, and PGs (P < .001). In comparison with lesions with inflammatory
      infiltrates grades I and II, lesions with inflammatory infiltrate grade III
      exhibited a higher number of FoxP3+ cells (P = .002). Similarly, in comparison
      with lesions with inflammatory infiltrates grades II and III, lesions with
      inflammatory infiltrate grade I showed a tendency for a lower expression of IL-17
      and TGF-beta1 (P = .085 and P = .051, respectively). For all groups, there was a
      positive correlation between the immunoexpressions of IL-17 and TGF-beta1 (P <
      .05). Positive correlations between the number of FoxP3+ cells and the
      immunoexpressions of IL-17 and TGF-beta1 (P < .05) were found only in PGs.
      CONCLUSIONS: Th17 and Treg cells seem to interact at the site of injury,
      suggesting the involvement of proinflammatory and immunoregulatory cytokines in
      the pathogenesis of periapical lesions.

PMID- 23880266
TI  - Nuclear expression of p27(Kip1) is associated with in vivo differentiation of
      adult human odontoblasts.
AB  - INTRODUCTION: Odontoblasts are terminally differentiated cells of ectomesenchymal
      origin that produce the dentin. Differentiated odontoblasts cannot be identified
      yet by a single phenotypic marker protein; therefore, a combination of markers is
      currently used. Up-regulation of the cyclin-dependent kinase inhibitor p27(Kip1)
      has been associated with exit from the cell cycle and terminal differentiation of
      mammalian cells. Immunoreactivity for p27(Kip1) protein was shown in many adult
      mouse tissues, but no information is available on the expression of p27(Kip1) in
      mammalian dental pulp. METHODS: Healthy and carious adult human molars with
      reparative dentin formation were decalcified, cryoprotected, frozen embedded, and
      frozen sectioned. The expression of p27(Kip1) and nestin in cells of adult human
      dental pulp was analyzed by immunohistochemistry using free floating sections.
      RESULTS: p27(Kip1) showed strong nuclear expression in many differentiated human
      molar odontoblasts at the odontoblastic layer. Most cells of the cell-rich zone
      displayed low levels of p27(Kip1) despite the fact that preodontoblasts localized
      in the cell-rich zone of the subodontoblastic layer have been identified as
      quiescent cells. The nuclear expression of p27(Kip1) in stromal cells of the
      dental pulp was variable, indicating that subpopulations of these cells were in
      distinct states of differentiation. Odontoblasts generating reparative dentin
      showed comparable nuclear expression of p27(Kip1) in comparison with odontoblasts
      synthesizing primary/secondary dentin. This result indicates that odontoblasts
      synthesizing primary/secondary or reparative dentin exhibit a similar
      differentiation status. CONCLUSIONS: Our findings show that increased expression
      of nuclear p27(Kip1) occurred during differentiation from preodontoblasts to
      odontoblasts in adult healthy and carious molars. p27(Kip1) can be used as a
      novel nuclear marker protein for differentiated human odontoblasts in vivo.

PMID- 23880267
TI  - Glycol chitin-based thermoresponsive hydrogel scaffold supplemented with enamel
      matrix derivative promotes odontogenic differentiation of human dental pulp
      cells.
AB  - INTRODUCTION: Hydrogels have been widely studied as tissue engineering scaffolds
      over the past 2 decades because of their favorable biological properties.
      Recently, a new biodegradable glycol chitin-based thermoresponsive hydrogel
      scaffold (GC-TRS) was developed that can be easily applied as a mild viscous
      solution at room temperature but quickly transforms into a durable hydrogel under
      physiological conditions. The aim of this study was to investigate the effects of
      GC-TRS on the proliferation and odontogenic differentiation of colony-forming
      human dental pulp cells (hDPCs) in the presence of enamel matrix derivative.
      METHODS: Glycol chitin was synthesized by N-acetylation of glycol chitosan. The
      morphology of the thermoresponsive hydrogel scaffold was observed by using
      scanning electron microscopy. The sol gel phase transition of the aqueous
      solution of glycol chitin was investigated by using the tilting method and
      rheometer studies. hDPCs were isolated based on their ability to generate
      clonogenic adherent cell clusters. The effect of GC-TRS and collagen on cell
      viability was examined by performing 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Expression of markers for
      odontogenic/osteogenic differentiation (ie, dentin sialophosphoprotein, dentin
      matrix protein-1, osteonectin, and osteopontin) was analyzed by performing real
      time polymerase chain reaction. RESULTS: GC-TRS exhibited a highly macroporous
      and well-interconnected porous structure. The polymer solution existed in a
      mildly viscous sol state, but it transitioned to a gel state and did not flow
      above approximately 37 degrees C. Rheometer studies showed that the glycol chitin
      solution exhibited a fast sol gel transition approximately at body temperature.
      GC-TRS and collagen did not inhibit cell viability until 7 days. Dentin
      sialophosphoprotein and dentin matrix protein-1 were expressed by cells cultured
      in GC-TRS at a higher level than that in cells cultured in collagen (P < .05). In
      both the scaffold groups, dentin sialophosphoprotein, dentin matrix protein-1,
      and osteopontin messenger RNA was up-regulated significantly in EMD-treated hDPCs
      when compared with the nontreated cells (P < .05). CONCLUSIONS: GC-TRS allowed
      the proliferation and odontogenic differentiation of hDPCs. Furthermore, the
      differentiation was facilitated by EMD. These results suggest that GC-TRS has the
      potential to be used in tissue engineering techniques for dentin regeneration.

PMID- 23880268
TI  - Lipopolysaccharide-binding protein inhibits toll-like receptor 2 activation by
      lipoteichoic acid in human odontoblast-like cells.
AB  - INTRODUCTION: Previous studies have suggested that odontoblasts sense gram
      positive bacteria components through Toll-like receptor 2 (TLR2) and trigger
      dental pulp immunity by producing proinflammatory cytokines. Currently, the
      factors that modulate odontoblast TLR2 activation are unknown. Our aim was to
      investigate lipopolysaccharide-binding protein (LBP) effects on the TLR2-mediated
      odontoblast response. METHODS: Human odontoblast-like cells were stimulated with
      lipoteichoic acid (LTA) (a TLR2 ligand), LBP, CD14 (a TLR2 cofactor), or various
      combinations of LTA/LBP, LTA/CD14, or LTA/CD14/LBP. CXCL8, IL6, and TLR2 gene
      expression was assessed by real-time polymerase chain reaction. CXCL8 and
      interleukin (IL)-6 production was determined by enzyme-linked immunosorbent assay
      in culture supernatants of cells stimulated with LTA, LTA/CD14, or LTA/CD14/LBP.
      LBP effects on nuclear factor kappa B (NF-kappaB), p38, JNK, ERK, STAT3, and
      p70S6 signaling pathways were determined in LTA-stimulated odontoblast-like cells
      with a multiplex biometric immunoassay. LBP effects were compared with specific
      inhibitors of these signaling pathways. LBP transcript and protein were
      investigated in vivo in healthy and inflamed dental pulps by real-time polymerase
      chain reaction and immunohistochemistry. RESULTS: Activation of CXCL8, IL6, and
      TLR2 gene expression and CXCL8 and IL-6 secretion in LTA- and LTA/CD14-stimulated
      odontoblast-like cells was significantly decreased by LBP. LBP inhibited NF
      kappaB and p38 signaling pathways in LTA-stimulated cells in a similar way to NF
      kappaB and p38 inhibitors. LBP transcript and protein were detected in vivo in
      inflamed dental pulps but not in healthy ones. CONCLUSIONS: These results
      demonstrate that LBP reduces TLR2-dependent production of inflammatory cytokines
      by odontoblast-like cells. We suggest that in this way it could modulate host
      defense in human dental pulp.

PMID- 23880269
TI  - Conditioned medium from periapical follicle cells induces the odontogenic
      differentiation of stem cells from the apical papilla in vitro.
AB  - INTRODUCTION: We investigated the biological effects of conditioned medium (CM)
      from periapical follicle cells (PAFCs) of root-developing tooth on the
      proliferation and differentiation of stem cells from the apical papilla (SCAP) in
      vitro. METHODS: Human SCAP and PAFCs were isolated and expanded. CM from PAFCs
      was prepared with the primary cells. Cell cycle analysis, methyl-thiazol
      diphenyltetrazolium assay, alkaline phosphatase activity, mineralization
      behavior, and gene expression of odontoblast phenotype SCAP cultured with or
      without CM from PAFCs were evaluated. RESULTS: In the CM-treated group, the cell
      growth, alkaline phosphatase activity, and mineralization of SCAP were up
      regulated. The expression of dentin sialophosphoprotein, alkaline phosphatase,
      and osteocalcin mRNA progressively increased in SCAP treated with CM from PAFCs.
      CONCLUSIONS: Our findings suggest that CM from PAFCs is able to provide a
      favorable odontogenic microenvironment to induce differentiation of SCAP along
      the odontoblast lineage.

PMID- 23880270
TI  - Role of the extracellular signal-regulated kinase 1/2 pathway in driving
      tricalcium silicate-induced proliferation and biomineralization of human dental
      pulp cells in vitro.
AB  - INTRODUCTION: The aim of this study was to investigate the role of the
      extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in regulating
      tricalcium silicate (C3S)-driven proliferation and biomineralization of human
      dental pulp cells (hDPCs) in vitro. METHODS: Human DPCs were cultured in C3S
      containing medium and compared with untreated controls. Cell viability was
      measured by the methyl-thiazol-tetrazolium assay. Biomineralization was assessed
      by staining calcium deposits on the extracellular matrix with von Kossa and
      alizarin red S stains. Phosphorylated ERK1/2 was evaluated by immunoblotting. The
      ERK1/2 inhibitor U0126 was used to assess the role of this pathway on stage of
      the cell cycle and mineralization-dependent gene expressions of hDPCs by using
      flow cytometry and real-time polymerase chain reaction, respectively. Data were
      analyzed by analysis of variance followed by the Student-Newman-Keuls post hoc
      test, with significance set at P < .05. RESULTS: The viability and
      biomineralization of hDPCs were promoted by C3S extracts (P < .05).
      Phosphorylated ERK1/2 strongly appeared after hDPCs were cultured in the C3S
      extracts for 30 minutes. Moreover, inhibition of the ERK1/2 pathway in C3S
      treated hDPCs decreased proliferation and the expression of mineralization
      dependent genes, including collagen type I, dentin sialophosphoprotein,
      osteopontin, and osteocalcin (P < .05). CONCLUSIONS: C3S stimulated the
      proliferation and biomineralization of hDPCs in vitro, with the ERK1/2 pathway
      playing a key role in the regulation of these effects.

PMID- 23880271
TI  - The biological performance of calcium hydroxide-loaded microcapsules.
AB  - INTRODUCTION: Calcium hydroxide (Ca[OH]2) microcapsules were synthesized for use
      in controlled release. The aim of this study was to evaluate the cytotoxicity,
      antibacterial properties, and influence on gene expression of bone-related
      markers of 2 different formulas of Ca(OH)2 microcapsules. METHODS: Two formulas
      of Ca(OH)2 microcapsules (A and B) were evaluated, and pure Ca(OH)2 powder was
      used as a positive control. The shell material of formula A was pure EC, and the
      PLA/EC blend of 1:1 was used as the shell material for formula B. The MG63
      cells/Cell Counting Kit-8 (Dojindo, Kumamoto, Japan) were used to evaluate the
      cytotoxicity, and the colony-forming units of Enterococcus faecalis were
      monitored for the antibacterial effect. The relative messenger RNA expression of
      collagen I and osteocalcin was determined by real-time polymerase chain reaction.
      RESULTS: Both formulas of the Ca(OH)2 microcapsules showed no cytotoxicity in
      MG63 cells; however, the Ca(OH)2 positive control did exhibit cytotoxicity. The
      antibacterial effect of the 2 microcapsule formulas lasted longer than the
      positive control, and formula A lasted longer than formula B. For both Ca(OH)2
      microcapsule formulas, the relative messenger RNA expression of collagen I and
      osteocalcin was prolonged and up-regulated. The time effects of the influence on
      messenger RNA expression of collagen I and osteocalcin were different between the
      2 microcapsule formulas. CONCLUSIONS: Ca(OH)2 microcapsules had prolonged
      antibacterial activity and prolonged the up-regulation of bone-related markers
      with reduced cytotoxicity.

PMID- 23880272
TI  - Antimicrobial effect of a modified vanadium chloroperoxidase on Enterococcus
      faecalis biofilms at root canal pH.
AB  - INTRODUCTION: Previous research showed an antimicrobial effect of vanadium
      chloroperoxidase (VCPO) on in vitro Enterococcus faecalis biofilms. The current
      study aimed to optimize the use of this enzyme at the root canal pH using a
      modified VCPO (mVCPO) that was adapted to function at a higher pH and to explore
      the biocompatibility of mVCPO. METHODS: The activity of the original and modified
      VCPO was assessed using the monochlorodimedone assay. For antimicrobial
      assessment, 48-hour biofilms of E. faecalis OS-16 were incubated 5 or 30 minutes
      with mVCPO, bromide, and hydrogen peroxide, and colony-forming units were
      determined. A metabolic activity assay was used to evaluate the cytotoxic effect
      of mVCPO on oral fibroblasts. RESULTS: Reaction products generated by mVCPO at a
      root canal pH of 7.7 significantly inactivated the biofilm after 5 minutes and
      even more after 30 minutes (Mann-Whitney U test, P < .05). The mVCPO reaction
      products showed less cytotoxic effects than control solutions and 0.5% sodium
      hypochlorite (Kruskal-Wallis test, P < .05). CONCLUSIONS: The incubation of mVCPO
      in the presence of its substrates with in vitro E. faecalis biofilms showed a
      significant antimicrobial effect at the root canal pH. Also, cytotoxicity tests
      showed preliminary biocompatibility. Therefore, an interappointment dressing
      containing mVCPO could aid in improving current endodontic treatment through
      continuous and local generation of antimicrobials.

PMID- 23880273
TI  - Sodium hypochlorite with reduced surface tension does not improve in situ pulp
      tissue dissolution.
AB  - INTRODUCTION: Sodium hypochlorite (NaOCl) solutions with added wetting agents are
      advertised to dissolve necrotic tissue in root canals faster than their
      counterparts without a lowered surface tension. This was tested in the current
      study, and the null hypothesis formulated was that there was no difference
      between a commercially available NaOCl solution with a lowered surface tension
      (Chlor-XTRA; Vista Dental Products, Racine, WI) and a counterpart containing the
      same amount of available chlorine without added wetting agents regarding the soft
      tissue that remains in oval-shaped canals after mechanical preparation and
      irrigation. METHODS: Formerly vital extracted teeth (N = 44, 22 pairs) with
      similar anatomy were radiographically paired and chemomechanically prepared. In 1
      tooth from each pair, a 5.25% NaOCl solution with reduced surface tension was
      used; in the other, a pure, technical-grade NaOCl solution of 5.25% was used. The
      percentage of remaining pulp tissue (PRPT) was histologically assessed in root
      cross-sections. The non-Gaussian raw data were subjected to Kruskal-Wallis and
      Mann-Whitney U tests to verify the respective effect of the cross-section level
      and solution on the PRPT. The relationship between the cross-section level and
      the PRPT was estimated by the Spearman correlation test. The alpha-type error was
      set at 5%. RESULTS: The cross-section level significantly influenced the PRPT (P
      < .05), whereas the PRPT was not influenced by the solution used (P > .05). A
      significant inverse correlation was found between the cross-section level and the
      PRPT (P < .05, r = -0.330). The lower the distance to the apex, the higher the
      PRPT regardless of the solution used. CONCLUSIONS: Contrary to the advertised
      statement, the dental solution with a reduced surface tension did not dissolve
      vital pulp tissue in oval root canals any better than a conventional NaOCl
      solution of similar strength. Closer to the apex, pulp tissue dissolution is less
      efficient irrespective of the solution.

PMID- 23880274
TI  - Correlative bacteriologic and micro-computed tomographic analysis of mandibular
      molar mesial canals prepared by self-adjusting file, reciproc, and twisted file
      systems.
AB  - INTRODUCTION: This ex vivo study evaluated the disinfecting and shaping ability
      of 3 protocols used in the preparation of mesial root canals of mandibular molars
      by means of correlative bacteriologic and micro-computed tomographic (MUMUCT)
      analysis. METHODS: The mesial canals of extracted mandibular molars were
      contaminated with Enterococcus faecalis for 30 days and assigned to 3 groups
      based on their anatomic configuration as determined by MUCT analysis according to
      the preparation technique (Self-Adjusting File [ReDent-Nova, Ra'anana, Israel],
      Reciproc [VDW, Munich, Germany], and Twisted File [SybronEndo, Orange, CA]). In
      all groups, 2.5% NaOCl was the irrigant. Canal samples were taken before (S1) and
      after instrumentation (S2), and bacterial quantification was performed using
      culture. Next, mesial roots were subjected to additional MUCT analysis in order
      to evaluate shaping of the canals. RESULTS: All instrumentation protocols
      promoted a highly significant intracanal bacterial reduction (P < .001).
      Intergroup quantitative and qualitative comparisons disclosed no significant
      differences between groups (P > .05). As for shaping, no statistical difference
      was observed between the techniques regarding the mean percentage of volume
      increase, the surface area increase, the unprepared surface area, and the
      relative unprepared surface area (P > .05). Correlative analysis showed no
      statistically significant relationship between bacterial reduction and the mean
      percentage increase of the analyzed parameters (P > .05). CONCLUSIONS: The 3
      instrumentation systems have similar disinfecting and shaping performance in the
      preparation of mesial canals of mandibular molars.

PMID- 23880275
TI  - A comparison of dentin cutting efficiency of 4 round-tipped ultrasonic
      instruments.
AB  - INTRODUCTION: Ultrasonic instruments are available for a variety of endodontic
      uses. Few published evaluations exist that compare the dentin cutting efficiency
      of endodontic ultrasonic tips. Furthermore, previous comparison studies often did
      not take into account 2 critical factors: clinically relevant downward forces and
      linear movement during use. METHODS: Four different round-tipped ultrasonic tips
      were compared (n = 5 per tip group): BUC-1 (Obtura Spartan, Fenton, MO), BL-2
      (B&L Biotech, Bala Cynwyd, PA), BL-3 (B&L Biotech), and START-X #2 (Dentsply
      Maillefer, Ballaigues, Switzerland). The tips were attached to a testing
      apparatus that applied a 15-g axial force and a linear movement during
      instrumentation of a human dentin specimen. Instrumentation was completed at the
      manufacturers' recommended power settings, and 3 of the tips were also compared
      at an equal power setting. Instrumentation consisted of 20-second cycles for a
      total of 6 minutes. Dentin specimens were weighed at baseline and after 2, 4, and
      6 minutes of instrumentation. The dentin cutting efficiency was measured by the
      change in weight of dentin specimens to the nearest 0.1 mg. RESULTS: A 1-factor
      analysis of variance and Tukey post hoc analysis of cumulative dentin removal
      (after 6 minutes of instrumentation) revealed a statistically significant
      difference among the 4 ultrasonic tips (P <= .0001) at the recommended PS, with
      the BUC-1 tip removing significantly more dentin across time. At an equal power
      setting, the BUC-1 was significantly more efficient than the BL-3; no difference
      was found between the BUC-1 and the BL-2. CONCLUSIONS: Within the limits of this
      study, the BUC-1 showed the greatest dentin removal. Adding a linear movement and
      a clinically relevant axial force allows better generalization to clinical
      applications.

PMID- 23880276
TI  - The incidence of root microcracks caused by 3 different single-file systems
      versus the ProTaper system.
AB  - INTRODUCTION: The aim of this study was to compare the incidence of root cracks
      observed at the apical root surface and/or in the canal wall after canal
      instrumentation with 3 single-file systems and the ProTaper system (Dentsply
      Maillefer, Ballaigues, Switzerland). METHODS: One hundred mandibular incisors
      were selected. Twenty control teeth were coronally flared with Gates-Glidden
      drills (Dentsply Maillefer). No further preparation was made. The other 80 teeth
      were mounted in resin blocks with simulated periodontal ligaments, and the apex
      was exposed. They were divided into 4 experimental groups (n = 20); the root
      canals were first coronally flared with Gates-Glidden drills and then
      instrumented to the full working length with the ProTaper, OneShape (Micro-Mega,
      Besancon, France), Reciproc (VDW, Munich, Germany), or the Self-Adjusting File
      (ReDent-Nova, Ra'anana, Israel). The apical root surface and horizontal sections
      2, 4, and 6 mm from the apex were observed under a microscope. The presence of
      cracks was noted. The chi-square test was performed to compare the appearance of
      cracked roots between the experimental groups. RESULTS: No cracks were found in
      the control teeth and teeth instrumented with the Self-Adjusting File. Cracks
      were found in 10 of 20 (50%), 7 of 20 (35%), and 1 of 20 (5%) teeth after canal
      instrumentation with the ProTaper, OneShape, and Reciproc files, respectively.
      The difference between the experimental groups was statistically significant (P <
      .001). CONCLUSIONS: Nickel-titanium instruments may cause cracks on the apical
      root surface or in the canal wall; the Self-Adjusting File and Reciproc files
      caused less cracks than the ProTaper and OneShape files.

PMID- 23880277
TI  - Comparison of efficacy of pulverization and sterile paper point techniques for
      sampling root canals.
AB  - INTRODUCTION: The purpose of this study was to compare the efficacy of the
      pulverization and sterile paper point techniques for sampling root canals using
      5.25% NaOCl/17% EDTA and 1.3% NaOCl/MTAD (Dentsply, Tulsa, OK) as irrigation
      regimens. METHODS: Single-canal extracted human teeth were decoronated and
      infected with Enterococcus faecalis. Roots were randomly assigned to 2 irrigation
      regimens: group A with 5.25% NaOCl/17% EDTA (n = 30) and group B with 1.3%
      NaOCl/MTAD (n = 30). After chemomechanical debridement, bacterial samplings were
      taken using sterile paper points and pulverized powder of the apical 5 mm root
      ends. RESULTS: The sterile paper point technique did not show growth in any
      samples. The pulverization technique showed growth in 24 of the 60 samples. The
      Fisher exact test showed significant differences between sampling techniques (P <
      .001). The sterile paper point technique showed no difference between irrigation
      regimens. However, 17 of the 30 roots in group A and 7 of the 30 roots in group B
      resulted in growth as detected by pulverization technique. Data showed a
      significant difference between irrigation regimens (P = .03) in pulverization
      technique. CONCLUSIONS: The pulverization technique was more efficacious in
      detecting viable bacteria. Furthermore, this technique showed that 1.3%
      NaOCl/MTAD regimen was more effective in disinfecting root canals.

PMID- 23880278
TI  - Micro-computed tomography study of oval-shaped canals prepared with the self
      adjusting file, Reciproc, WaveOne, and ProTaper universal systems.
AB  - INTRODUCTION: The newly developed single-file systems claimed to be able to
      prepare the root canal space with only 1 instrument. The present study was
      designed to test the null hypothesis that there is no significant difference in
      the preparation of oval-shaped root canals using single- or multiple-file
      systems. METHODS: Seventy-two single-rooted mandibular canines were matched based
      on similar morphologic dimensions of the root canal achieved in a micro-computed
      tomographic evaluation and assigned to 1 of 4 experimental groups (n = 18)
      according to the preparation technique (ie, Self-Adjusting File [ReDent-Nova,
      Ra'anana, Israel], WaveOne [Dentsply Maillefer, Ballaigues, Switzerland],
      Reciproc [VDW, Munich, Germany], and ProTaper Universal [Dentsply Maillefer]
      systems). Changes in the 2- and 3-dimensional geometric parameters were compared
      with preoperative values using analysis of variance and the post hoc Tukey test
      between groups and the paired sample t test within groups (alpha = 0.05).
      RESULTS: Preparation significantly increased the analyzed parameters; the outline
      of the canals was larger and showed a smooth taper in all groups. Untouched areas
      occurred mainly on the lingual side of the middle third of the canal. Overall, a
      comparison between groups revealed that SAF presented the lowest, whereas WaveOne
      and ProTaper Universal showed the highest mean increase in most of the analyzed
      parameters (P < .05). CONCLUSIONS: All systems performed similarly in terms of
      the amount of touched dentin walls. Neither technique was capable of completely
      preparing the oval-shaped root canals.

PMID- 23880279
TI  - Reciprocating root canal technique induces greater debris accumulation than a
      continuous rotary technique as assessed by 3-dimensional micro-computed
      tomography.
AB  - INTRODUCTION: The ability of single-file, reciprocating instruments to remove
      inorganic debris is uncertain. By using micro-computed tomography (microCT), this
      study compared the 3-dimensional distribution, quantity, and density of remaining
      inorganic debris in the mesial root of mandibular molars after instrumentation. A
      single reciprocating file was compared with a multifile rotary instrumentation
      technique. METHODS: Teeth were selected for instrumentation using reciprocating
      or rotary instruments (n = 19). Teeth were scanned using microCT before and after
      instrumentation. Through shape recognition and superimposition image analysis
      techniques, remaining inorganic tissue debris was identified, quantified, and
      visualized 3-dimensionally, mapping debris to its location. The use of a density
      phantom enabled the debris density to be calculated, giving a measure of
      compactness. RESULTS: After single-file instrumentation, an average of 19.5%
      debris remained in the canal compared with 10.6% with the multifile technique (P
      = .01) and at an average density of 1.60 g/m(3) compared with 1.55 g/m(3) for the
      multifile system (P > .05). Isthmuses, protrusions, and irregularities in the
      canal wall were repeatedly seen at the locations of debris accumulation.
      CONCLUSIONS: In canals with a high prevalence of isthmuses and protrusions, using
      multifile rotary systems may be preferred over reciprocating files because it can
      yield cleaner canals with less debris accumulation.

PMID- 23880280
TI  - An evaluation of setting time of mineral trioxide aggregate and EndoSequence root
      repair material in the presence of human blood and minimal essential media.
AB  - INTRODUCTION: The purpose of this study was to compare the ability of MTA
      (Dentsply Maillefer, Tulsa, OK) and EndoSequence Root Repair Material (ESRRM;
      Brasseler USA, Savannah, GA) to set in the presence of human blood and minimal
      essential media. METHODS: A model was created using polymethyl methacrylate
      blocks each prepared with 10 standardized wells (2-mm diameter * 3-mm depth).
      Prepared ProRoot MTA (Dentsply Maillefer) and ESRRM were each placed in 6
      separate blocks. The samples were distributed among the 4 different media (ie,
      blood, minimal essential media, blood and minimal essential media, and sterile
      saline as the control). Each block was submerged for 4, 5, 6, 8, 24, 36, and 48
      hours in an incubator at 37 degrees C with 100% humidity. RESULTS: The results
      revealed that regardless of the type of media exposure, neither of the materials
      set at 4 or 6 hours. ESRRM was not set at 48 hours, whereas all of the MTA
      samples were set at 36 hours. CONCLUSIONS: This outcome draws into question the
      proposed setting time given by each respective manufacturer. Furthermore, despite
      ESRRM being marketed as a direct competitor to MTA with superior handling
      properties, MTA consistently set at a faster rate under the conditions of this
      study.

PMID- 23880281
TI  - Endodontic and surgical treatment of root damage caused by orthodontic miniscrew
      placement.
AB  - INTRODUCTION: Miniscrews are being increasingly used for anchorage control in
      orthodontics. Despite the concern over root damage caused by miniscrews, there
      are few reports of precise clinical evaluations and appropriate management of
      that damage. In the case presented herein, the root damage caused by the
      placement of miniscrews was repaired by root canal treatment and surgical
      intervention. METHODS: A 44-year-old man received orthodontic treatment for
      intrusion of the left maxillary first molar with a miniscrew anchorage system.
      During that treatment, the miniscrews had fallen out and had to be reinserted
      more than 6 times in the same area. Two years later, the patient complained of a
      spontaneous pain in the maxillary left molar region. Although the patient
      received root canal treatment, intraoral sinus tracts could still be detected,
      and the patient's discomfort persisted. Periradicular surgery revealed that the
      persistent infection was related to root surface damage caused by orthodontic
      miniscrew placement. Healing was achieved by a combination of root canal
      treatment and surgical intervention. RESULTS: Scanning electron microscopy of the
      damaged distobuccal root apex revealed a mature biofilm consisting of a network
      of matrix that contained mostly rod-like and spherical bacteria. At a 12-month
      recall checkup, the patient was free of pain. A repeat periapical radiograph
      revealed reduction of the pretreatment radiolucent lesion. CONCLUSIONS: More
      careful planning of miniscrew placement is necessary to lessen the danger of root
      damage. Furthermore, a precise evaluation of both root and pulpal damage and
      careful consideration of the choice of optimal treatment modality are needed.

PMID- 23880282
TI  - Clinical, radiographic, and histological observation of a human immature
      permanent tooth with chronic apical abscess after revitalization treatment.
AB  - INTRODUCTION: Revitalization procedures have been widely used for the treatment
      of immature permanent teeth with apical periodontitis. The treatment procedures
      appear to be capable of encouraging continued root development and thickening of
      the canal walls. The nature of tissues formed in the canal space and at the root
      apex after revitalization has been shown histologically in several animal
      studies; similar studies in humans were recently reported. METHODS: A 9-year-old
      boy had a traumatic injury to his upper anterior teeth. Tooth #9 suffered a
      complicated crown fracture with a pulp exposure, which was restored with a
      composite resin. The tooth developed a chronic apical abscess. Revitalization
      procedures were performed on tooth #9 because it was an immature permanent tooth
      with an open apex and thin canal walls. Twenty-six months after revitalization,
      the tooth had a horizontal crown fracture at the cervical level and could not be
      restored. The tooth was extracted and processed for routine histological and
      immunohistochemical examination to identify the nature of tissues formed in the
      canal space. RESULTS: Clinically and radiographically, the revitalization of the
      present case was successful because of the absence of signs and symptoms and the
      resolution of periapical lesion as well as thickening of the canal walls and
      continued root development. The tissue formed in the canal was well-mineralized
      cementum- or bone-like tissue identified by routine histology and
      immunohistochemistry. No pulp-like tissue characterized by the presence of
      polarized odontoblast-like cells aligning dentin-like hard tissue was observed.
      CONCLUSIONS: The tissues formed in the canal of revitalized human tooth are
      similar to cementum- or bone-like tissue and fibrous connective tissue.

PMID- 23880283
TI  - A case of coinfection in a chronic maxillary sinusitis of odontogenic origin:
      identification of Dialister pneumosintes.
AB  - INTRODUCTION: In this report, we discuss the case of a 39-year-old woman
      presenting with a case of chronic maxillary sinusitis. METHODS: Dialister
      pneumosintes, Staphylococcus epidermidis, and Peptostreptococcus spp. were
      isolated from endosinusal samples obtained during surgery. The patient showed
      extensive periodontopathy and had undergone prior endodontic treatment for
      endodontic infection of teeth #13, #14, and #15, which failed and presumably
      acted as a bridge for the sinusal infection. After nasosinusal surgery,
      consisting of opening and toilet of the maxillary sinus, combined with extraction
      of the 3 previously mentioned teeth and antibiotic treatment, the patient showed
      complete healing. RESULTS: S. epidermidis and Peptostreptococcus spp. were
      identified with a traditional biochemical test and confirmed by pyrosequencing.
      Conversely, D. pneumosintes could not be identified with the conventional method,
      but it was identified using DNA pyrosequencing. In addition, to better understand
      the role and the virulence of this bacterium in odontogenic sinusitis, we have
      evaluated the ability of D. pneumosintes to produce biofilms onto inert surfaces.
      D. pneumosintes is a known endodontic and periodontal pathogen found in necrotic
      pulp, subgingival plaque, and deep periodontal pockets. CONCLUSIONS: To our
      knowledge, the pathogenic role of D. pneumosintes in odontogenic sinusitis has
      never been evidenced. Thus, its detection in endosinusal specimens may provide a
      significant insight into the pathogenesis of this relevant medical condition.

PMID- 23880285
TI  - Distribution of dihydrofolate reductase (dhfr) and dihydropteroate synthase
      (dhps) mutant alleles in Plasmodium vivax isolates from Thailand.
AB  - The analysis of prevalence and distribution of pvdhfr and pvdhps mutations were
      performed in 169 samples collected from patients with Plasmodium vivax infection
      who attended the malaria clinics in the provinces along the three international
      borders of Thailand (Thai-Myanmar, Thai-Cambodian, and Thai-Malaysian borders).
      SNP-haplotypes of the pvdhfr at amino acid positions 13, 33, 57, 58, 61, 117, and
      173 and of the pvdhps at positions 383 and 553 were examined by nested PCR-RFLP.
      Significant differences in the prevalence and distribution of pvdhfr and pvdhps
      combination alleles were observed in P. vivax isolates collected from all the
      three border areas. The most prevalent combination alleles were triple mutant
      pvdhfr 57L/58R/117T alleles/double wild-type pvdhps alleles (n=18), double mutant
      pvdhfr 58R/117N alleles/double wild-type pvdhps alleles (n=10), and triple mutant
      pvdhfr 58R/61M/117N alleles/double wild-type pvdhps alleles (n=52) or with single
      mutant pvdhps 383G allele (n=28), respectively. These information on prevalence
      and patterns of pvdhfr and pvdhps polymorphisms obtained from the present study
      suggest the presence of SP pressure on P. vivax isolates in Thailand which could
      be linked to the introduction of malaria from neighboring countries. Results did
      not support the application of SP for P. vivax control program in Thailand as
      well as the neighboring countries. 

PMID- 23880284
TI  - Oral cutaneous sinus tract, vertical root fracture, and bisphosphonate-related
      osteonecrosis: a case report.
AB  - INTRODUCTION: Oral cutaneous sinus tracts (OCSTs) of dental origin are often
      initially misdiagnosed and inappropriately treated. Accurate diagnosis is
      especially important in cases of bisphosphonate (BP) therapy because extraction
      may lead to a risk of osteonecrosis. A case report of misdiagnosis related to a
      tooth with a vertical root fracture in an oncologic patient treated with BPs is
      reported here. METHODS: In 2011, a 75-year-old woman was examined at the oral
      medicine clinic because of pain and swelling of the left submandibular area. The
      patient's medical history included oral and intravenous BP therapy because she
      was diagnosed with metastatic breast cancer and left maxillary stage 1
      antiresorptive agent-induced osteonecrosis of the jaw. The lower left odontogenic
      region showed no signs or symptoms, and no apical pathosis was observed on
      imaging. Although antibiotics were applied, clinical symptoms worsened and an
      OCST appeared. Intravenous antibiotic treatment was pursued. Biopsy and direct
      smear from fistula were not conclusive. A diagnosis of a nonexposed variant of
      stage 3 antiresorptive agent-induced osteonecrosis of the jaw was established.
      RESULTS: Symptoms resolved after 2 weeks of antibiotic treatment and reappeared a
      month later. Endodontic examination revealed that the origin of the OCST was
      tooth no. 18 caused by a vertical root fracture, and the tooth was extracted. The
      patient was scheduled for routine checkups because of the fact that osteonecrosis
      may occur in intravenous BP-treated patients. CONCLUSIONS: Early correct
      diagnosis can prevent unnecessary and ineffective antibiotic therapy and surgical
      intervention, which is not recommended in intravenous BP cases.

PMID- 23880286
TI  - Benznidazole treatment in chronic children infected with Trypanosoma cruzi:
      serological and molecular follow-up of patients and identification of Discrete
      Typing Units.
AB  - A total of 221 children from two rural settlements in Northeast Argentina were
      examined for T. cruzi infection. Blood samples were taken for serology tests and
      PCR assays. In addition, T. cruzi Discrete Typing Units (DTUs) were determined by
      hybridization with specific DNA probes of the minicircle hypervariable regions
      (mHVR). Serological results indicated that 26% (57/215) were reactive against T.
      cruzi antigens. PCR analyses were performed on seropositive samples showing
      presence of parasite DNA in 31 out of 53 samples (58.5%). All seropositive
      children underwent specific chemotherapy with Benznidazole (5mg/kg/day) for a
      period of two months and were monitored two and five years after treatment.
      Overall the treatment was well tolerated and low side effects were observed.
      Serological conversion was observed at two years post -treatment in one child
      form Pampa Avila and at five years in two children from Tres Estacas. However, at
      the end of the follow-up period, T. cruzi DNA could not be detected by PCR in
      samples from treated children, except in two cases. In addition, the results of
      hybridizations with specific DNA probes showed that DTU TcV was detected in 68%
      (21/31), TcVI in 7% (2/31) and TcV/VI in 3% (1/31) of the samples. Altogether,
      results of the follow-up of treated children showed a low rate of seroconversion;
      however trend toward seroconversion was evident at five years post-treatment. On
      the other hand, detection of T. cruzi DNA by PCR significantly decreased after
      Benznidazole treatment. The existence of data regarding serological and molecular
      follow-ups from controlled studies in the Chaco Region will be important for
      future treatment efforts against T. cruzi infection in this region. The results
      obtained in the present study represent a contribution in this regard. 

PMID- 23880287
TI  - Differentiation between non-neural and neural contributors to ankle joint
      stiffness in cerebral palsy.
AB  - BACKGROUND: Spastic paresis in cerebral palsy (CP) is characterized by increased
      joint stiffness that may be of neural origin, i.e. improper muscle activation
      caused by e.g. hyperreflexia or non-neural origin, i.e. altered tissue
      viscoelastic properties (clinically: "spasticity" vs. "contracture").
      Differentiation between these components is hard to achieve by common manual
      tests. We applied an assessment instrument to obtain quantitative measures of
      neural and non-neural contributions to ankle joint stiffness in CP. METHODS:
      Twenty-three adolescents with CP and eleven healthy subjects were seated with
      their foot fixated to an electrically powered single axis footplate. Passive ramp
      and-hold rotations were applied over full ankle range of motion (RoM) at low and
      high velocities. Subject specific tissue stiffness, viscosity and reflexive
      torque were estimated from ankle angle, torque and triceps surae EMG activity
      using a neuromuscular model. RESULTS: In CP, triceps surae reflexive torque was
      on average 5.7 times larger (p = .002) and tissue stiffness 2.1 times larger (p =
      .018) compared to controls. High tissue stiffness was associated with reduced RoM
      (p < .001). Ratio between neural and non-neural contributors varied substantially
      within adolescents with CP. Significant associations of SPAT (spasticity test)
      score with both tissue stiffness and reflexive torque show agreement with
      clinical phenotype. CONCLUSIONS: Using an instrumented and model based approach,
      increased joint stiffness in CP could be mainly attributed to higher reflexive
      torque compared to control subjects. Ratios between contributors varied
      substantially within adolescents with CP. Quantitative differentiation of neural
      and non-neural stiffness contributors in CP allows for assessment of individual
      patient characteristics and tailoring of therapy.

PMID- 23880289
TI  - Mechanisms and therapeutic implications of the placebo effect in neurological and
      psychiatric conditions.
AB  - The power of a placebo to effect clinically meaningful neurobiological change
      comparable to pharmacological therapies has been demonstrated, although the
      mechanisms are not fully understood. Predicting placebo responsiveness has only
      recently received more attention, but psychological disposition, contextual and
      biological factors are now known to dramatically affect a person's susceptibility
      to the placebo effect. The placebo effect depends upon expectancies that can be
      modified in a number of ways, including conditioning through explicit or implicit
      learned associations. Based on the dopaminergic response to anticipation of
      benefit in Parkinson's disease, it was suggested that the placebo effect can be
      seen as analogous to the expectation of reward. Dopaminergic pathways have since
      been implicated in the placebo response in pain and depression. Additionally,
      endogenous opioid release is known to mediate many forms of placebo analgesia. We
      provide an overview of the mechanisms and the therapeutic implications of the
      placebo effect in neurological and psychiatric conditions. We include evidence
      for detrimental effects arising from seemingly inert interventions, termed the
      'nocebo effect.' Neuroimaging has critically advanced the study of the placebo
      effect and provides some of the strongest evidence for the mechanisms of this
      phenomenon prevalent across an array of human health-related circumstances. This
      review specifically focuses on mechanisms of the placebo effect in the three
      conditions that have most significantly demonstrated this effect and for which a
      plausible physiological basis can be identified: pain, PD and depression. Other
      neurological and psychiatric diseases reviewed include multiple sclerosis,
      Huntington's disease, Alzheimer's disease, schizophrenia and epilepsy. 

PMID- 23880288
TI  - Treating neutrophilic inflammation in COPD by targeting ALX/FPR2 resolution
      pathways.
AB  - Neutrophilic inflammation persists in COPD despite best current therapies and it
      is particularly resistant to inhaled glucocorticosteroids. Persistent neutrophil
      activation not only contributes to matrix breakdown, but can maintain
      inflammation through the release of endogenous damage associated molecule
      patterns (DAMPs). Inhibiting excessive neutrophilic inflammation is challenging
      as many pathogen recognition receptors can initiate migration and the targeting
      of downstream signaling molecules may compromise essential host defense
      mechanisms. Here, we discuss new strategies to combat this inflammation in COPD
      by focusing on the anti-inflammatory role of ALX/FPR2 receptors. ALX/FPR2 is a
      promiscuous G-protein coupled receptor (GPCR) responding to lipid and peptide
      agonists that can either switch on acute inflammation or promote resolution of
      inflammation. We highlight this receptor as an emerging target in the
      pathogenesis of COPD because known ALX/FPR2 endogenous agonists are enriched in
      COPD. Serum Amyloid A (SAA) has recently been discovered to be abundantly
      expressed in COPD and is a potent ALX/FPR2 agonist that unlike almost all other
      inflammatory chemoattractants, is induced by glucocorticosteroids. SAA not only
      initiates lung inflammation via ALX/FPR2 but can allosterically modify this
      receptor so that it no longer transduces pro-resolving signals from endogenous
      lipoxins that would otherwise promote tissue healing. We propose that there is an
      imbalance in endogenous and microbial ALX/FPR2 receptor agonists in the inflamed
      COPD lung environment that oppose protective anti-inflammatory and pro-resolution
      pathways. These insights open the possibility of targeting ALX/FPR2 receptors
      using synthetic agonists to resolve persistent neutrophilic inflammation without
      compromising essential host defense mechanisms. 

PMID- 23880290
TI  - Bronchial epithelium as a target for innovative treatments in asthma.
AB  - Increasing evidence of a critical role played by the bronchial epithelium in
      airway homeostasis is opening new therapeutic avenues. Its unique situation at
      the interface with the environment suggests that the subtle regulation
      orchestrated by the epithelium between tolerance and specific immune response
      might be impaired in asthma. Airway mucus is acting as a physical and a
      biological fluid between the environment and the epithelium, synergistically
      moved by the cilia. In asthma, excessive mucus production is a hallmark of airway
      remodeling. Since many years we tried to therapeutically target mucus
      hypersecretion, but actually this option is still not achieved. The present
      review discusses the dynamic processes regulating airway mucus production. Airway
      inflammation is central in current asthma management. Understanding of how the
      airway epithelium influences the TH2 paradigm in response to deleterious agents
      is improving. The multiple receptors expressed by the airway epithelium are the
      transducers of the biological signals induced by various invasive agents to
      develop the most adapted response. Airway remodeling is observed in severe
      chronic airway diseases and may result from ongoing disturbance of signal
      transduction and epithelial renewal. Chronic airway diseases such as asthma will
      require assessment of these epithelial abnormalities to identify phenotypic
      characteristics associated with predicting a clinical benefit for epithelial
      directed therapies. 

PMID- 23880291
TI  - SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative
      damage induced by myocardial ischemia reperfusion injury.
AB  - Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system
      and causes mitochondrial oxidative stress. Silent information regulator 1
      (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a
      strong natural antioxidant and is the active component in Curcuma longa; Cur has
      protective effects against IRI and may regulate the activity of SIRT1. This study
      was designed to investigate the protective effect of Cur pretreatment on
      myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo
      rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior
      to this procedure, the hearts or cardiomyocytes were exposed to Cur in the
      absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred
      a cardioprotective effect, as shown by improved postischemic cardiac function,
      decreased myocardial infarct size, decreased myocardial apoptotic index, and
      several biochemical parameters, including the up-regulation of the antiapoptotic
      protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol
      and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting
      SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox
      potential, significantly elevated mitochondrial superoxide dismutase activity,
      and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde.
      These observations indicated that the IR-induced mitochondrial oxidative damage
      was remarkably attenuated. However, this Cur-elevated mitochondrial function was
      reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results
      demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced
      mitochondrial oxidative damage through the activation of SIRT1 signaling. 

PMID- 23880292
TI  - Fibrogenic actions of acetaldehyde are beta-catenin dependent but Wingless
      independent: a critical role of nucleoredoxin and reactive oxygen species in
      human hepatic stellate cells.
AB  - We investigated whether the fibrogenic actions of acetaldehyde, the immediate
      oxidation product of ethanol, are mediated via Wingless (WNT) and/or beta-catenin
      pathways in human hepatic stellate cells (HSC). First, we show that both beta
      catenin small inhibitory RNA and a dominant negative-MYC expression vector
      markedly down-regulated the expressions of fibrogenic genes in freshly isolated
      HSC. We further show that acetaldehyde up-regulated platelet-derived growth
      factor receptor beta mRNA and protein expressions ranging from 4.0- to 7.2-fold
      (P<0.001). Acetaldehyde induced MYC and collagen type-1 alpha-2 mRNA and protein
      expressions were WNT independent because DKK1, an antagonist of the canonical
      WNT/beta-catenin pathway, completely failed to block these inductions.
      Acetaldehyde increased phospho-glycogen synthase kinase-3 beta (GSK3B) protein by
      31% (P<0.01), whereas phospho-beta-catenin protein decreased by 50% (P <= 0.01).
      Significantly, in contrast to 43% (P<0.01) inhibition of beta-catenin nuclear
      translocation in nucleoredoxin (NXN)-overexpressed HSC, acetaldehyde profoundly
      stimulated beta-catenin nuclear translocation by 51%, (P<0.01). Acetaldehyde also
      increased the cellular reactive oxygen species level 2-fold (P<0.001) with a
      concomitant 2-fold (P<0.001) increase in 4-hydroxynonenal adducts. Conversely,
      there was a 44% decrease (P<0.001) in glutathione levels with a concomitant 76%
      (P<0.001) decrease in the level of NXN/ disheveled (DVL) complex. Based on these
      findings, we conclude that actions of acetaldehyde are mediated by a mechanism
      that inactivates NXN by releasing DVL, leading to the inactivation of GSK3B, and
      thereby blocks beta-catenin phosphorylation and degradation. Thus, the stabilized
      beta-catenin translocates to the nucleus where it up-regulates the fibrogenic
      pathway genes. This novel mechanism of action of acetaldehyde has the potential
      for therapeutic interventions in liver fibrosis induced by alcohol.

PMID- 23880293
TI  - Regulation of the Nrf2 antioxidant pathway by microRNAs: New players in
      micromanaging redox homeostasis.
AB  - MicroRNAs are now thought to play a central role in the regulation of many
      diverse aspects of cell biology; however, it remains to be fully elucidated how
      microRNAs can orchestrate cellular redox homeostasis, which plays a central role
      in a multitude of physiological and pathophysiological processes. The redox
      sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2)
      serves as a "master regulator" of cell survival through the coordinated induction
      of phase II and antioxidant defense enzymes to counteract oxidative stress and
      modulate redox signaling events. MicroRNAs are able to "fine-tune" the regulation
      of processes including those directly interacting with the Nrf2 pathway and the
      generation of reactive oxygen species (ROS). This review highlights that cellular
      redox homeostasis can be regulated by microRNAs through their modulation of Nrf2
      driven antioxidant gene expression as well as key enzymes that generate ROS,
      which in turn can alter the biogenesis and processing of microRNAs. Therefore
      redox sensitive microRNAs or "redoximiRs" add an important regulatory mechanism
      for redox signaling beyond the well-characterized actions of Nrf2. The potential
      exists for microRNA-based therapies where diminished antioxidant defenses and
      dysregulated redox signaling can lead to cardiovascular diseases, cancers,
      neurodegeneration, and accelerated aging. 

PMID- 23880294
TI  - Redox regulation of microRNAs in health and disease.

PMID- 23880295
TI  - IL-10, TNF-alpha & IFN-gamma: potential early biomarkers for preeclampsia.
AB  - The present study was designed to evaluate levels of IL4, IL10, TNF-alpha & IFN
      gamma at early second trimester and 24h from delivery to assess potential
      correlation of cytokine variation with preeclampsia. A total of 176 consecutive
      healthy, normotensive primigravidas with uncomplicated singleton pregnancies were
      recruited at 14-18weeks of gestation. Serum cytokine levels were estimated at
      recruitment and 24h from delivery. In present study, 14(7.95%) women developed
      preeclampsia. Levels of IL-10, TNF-alpha and IFN-gamma (Mean+/-SE) at recruitment
      were statistically significantly lower in preeclamptic group (39.21+/-9.46pg/mL,
      73.57+/-13.37pg/mL and 0.70+/-0.20pg/mL, respectively) than non-preeclamptic
      group (86.02+/-4.55pg/mL, 601.37+/-63.54pg/mL and 1.67+/-0.08pg/mL, respectively)
      (p<0.05). In preeclamptic group, IL-4 and TNF-alpha levels (Mean+/-SE) were
      significantly higher 24h from delivery (5.35+/-0.95pg/mL and 381.21+/-43.28pg/mL,
      respectively) than at recruitment (2.39+/-0.71pg/mL and 73.57+/-13.37pg/mL)
      (p=0.019 and 0.0001, respectively) while IL-10 and IFN-gamma levels decreased
      after delivery but the change was not statistically significant. Therefore, the
      levels of IL-10, TNF-alpha and IFN-gamma between 14 and 18weeks of gestation may
      act as potential early biomarkers in the diagnosis of preeclampsia. 

PMID- 23880296
TI  - Clinical implementation of adaptive hypofractionated bladder radiotherapy for
      improvement in normal tissue irradiation.
AB  - AIMS: Adaptive bladder radiotherapy, with plan of the day selection and plan
      library development based on individual filling patterns, has been previously
      modelled in patients receiving weekly hypofractionated treatment and improved
      geometric accuracy has been shown. The aim of this study was to assess the
      clinical implementation of the technique. MATERIALS AND METHODS: Conformal plans
      (with small, intermediate and large planning target volumes) were developed for
      25 patients. After pre-treatment cone-beam computed tomography, the optimal plan
      of the day was selected and delivered by two trained observers. Independent off
      line plan selection was also carried out. Concordance between the on-line and off
      line selections, frequency of plan usage, target coverage and normal tissue
      sparing were assessed. RESULTS: Plan selection concordance was 91%. Fifty-five
      per cent of fractions were delivered using small or large plans. The mean
      coverage of the clinical target volume by the 95% isodose was 99%. The mean
      reduction in the volume of normal tissue treated to 95% of the prescription dose
      was 219 cm(3) compared with the previous institutional standard approach.
      CONCLUSIONS: Good concordance in plan selection is shown with clinical
      implementation of the adaptive strategy. Adequate target coverage was achieved
      with reduction in the volume of normal tissue irradiated to a high dose compared
      with the previous standard approach.

PMID- 23880297
TI  - Cattle and sheep develop preference for drinking water containing grape seed
      tannin.
AB  - Ingestion of small amounts of some types of condensed tannins (CTs) by ruminant
      livestock can provide nutritional, environmental and economic benefits. However,
      practical methods are needed to make these tannins more available to ruminant
      livestock. Results from previous trials with crude quebracho and black wattle
      tannin indicated that cattle and/or sheep would not preferentially drink water
      containing these tannins. Therefore, we conducted preference trials to determine
      if cattle and sheep would learn to prefer water containing purified grape seed
      tannin (GST) that provided up to 2% of their daily dry matter (DM) intake. After
      gradual exposure to increasing amounts of this tannin in water during a pre-trial
      period, five adult ewes and five yearling heifers fed lucerne (Medicago sativa)
      pellets (19% CP) were offered water and several concentrations of GST solutions
      for either 15 (sheep trial) or 20 days (cattle trial). We measured intake of all
      liquids daily. Concentrations of blood urea were also measured for heifers when
      they drank only tannin solutions or water. Both sheep and cattle developed
      preferences for water with GST in it over water alone (P < 0.01) although this
      preference appeared earlier in the trial for sheep than for cattle. For the
      sheep, mean daily intake of water alone and all tannin solutions (in total) was
      0.6 and 6.1 l, respectively. For the cattle, mean daily intake of water and all
      tannin solutions in total was 21.8 and 20.6 l, respectively, in the first half of
      the trial and 10.8 and 26.1 l, respectively, in the second half of the trial.
      Compared with the other tannin solutions, both sheep and cattle drank more of the
      solution with the highest tannin concentration (2% of daily DM intake as GST)
      than of water on more trial days (P < 0.05). Ingestion of water with the highest
      concentration of GST reduced blood plasma urea concentration in the cattle by 9%
      to 14% (P <= 0.10) compared with ingestion of water alone. Results from the
      trials suggest that providing grape seed and perhaps other CTs via drinking water
      may be a practical way to introduce CTs into sheep and cattle diets.

PMID- 23880298
TI  - BiliCheck vs JM-103 in identifying neonates not at risk of hyperbilirubinaemia.
AB  - BACKGROUND: Transcutaneous bilirubinometry is widely used to predict
      hyperbilirubinemia by using several devices. The aim of this study was to compare
      the predictive ability of BiliCheck vs JM-103 in identifying neonates not at risk
      of significant hyperbilirubinemia, putting the data obtained with the two
      instruments on our transcutaneous bilirubin nomogram built with the BiliCheck.
      METHODS: Transcutaneous bilirubin (TcB) measurement was performed when jaundice
      appeared in newborn babies and/or just before discharge from the hospital. It was
      performed at the forehead with the two instruments within 5 minutes by two
      experienced neonatologists, each one blind to the value obtained by the other.
      Blood samples were drawn to obtain total serum bilirubin (TSB) levels soon after
      TcB measurements. RESULTS: A total of 627 paired-sample measurements were
      obtained from 298 newborn babies. Out of the total population studied, 16 newborn
      babies (5.4%) showed significant hyperbilirubinemia defined as TSB value >17
      mg/dL, or as need for phototherapy treatment according to the AAP guidelines. TcB
      measurements showed false negative results in the first 60 hours of life using
      both devices. After the 60th hour of life, TcB measurements using both devices
      successfully predicted newborn babies not at risk of significant
      hyperbilirubinemia, being the JM-103 more reliable than BC because of fewer false
      positive results. CONCLUSIONS: Our study shows that both BC and JM-103 can
      exclude subsequent significant hyperbilirubinemia when the measurements are
      performed after the 60th hour of life. Nevertheless, the transcutaneous pre
      discharge screening should be considered only as the first step, and it has to be
      followed by a follow-up through the first days after discharge.

PMID- 23880299
TI  - The bc:caa3 supercomplexes from the Gram positive bacterium Bacillus subtilis
      respiratory chain: a megacomplex organization?
AB  - The respiratory chain of some prokaryotes was shown to be organized in
      supercomplexes. This association has been proposed to improve enzyme stability
      and the overall efficiency of the oxidative phosphorylation process. Here, we
      have revisited recent data on the supercomplexes of Bacillus subtilis respiratory
      chain, by means of 1D and 2D-BN-PAGE, sucrose gradient fractionation of
      solubilized membranes, and mass spectrometry analysis of BN-PAGE bands detected
      in gel for succinate and cytochrome c oxidoreductase activities. The cytochrome
      bc:caa3 oxygen oxidoreductase supercomplex was observed in different
      stoichiometries, (bc)4:(caa3)2, (bc)2:(caa3)4 and 2[(bc)2:(caa3)4], suggesting
      for the first time the string association model of supercomplexes in a Gram
      positive bacterium. In addition, the presence of a succinate:quinone
      oxidoreductase:nitrate reductase supercomplex was confirmed by the co-localized
      succinate:nitroblue tetrazolium and methylviologen:nitrate oxidoreductase
      activities detected in gel and corroborated by LC-MS/MS analysis.

PMID- 23880300
TI  - 'Putting it together': unfolding case studies and high-fidelity simulation in the
      first-year of an undergraduate nursing curriculum.
AB  - The use of simulation as a teaching strategy in undergraduate nursing education
      is gaining increasing credibility and popularity. This article describes a study
      undertaken to evaluate first-year undergraduate nursing students' level of
      satisfaction with a new model of teaching clinical skills using unfolding case
      studies in a high-fidelity simulated clinical setting. The design incorporated a
      case study design conducted over 4 * 6 h simulation sessions. Participants
      included 47 first year Bachelor of Nursing Science students, three academic staff
      and two standardised patients. Findings from the study provide qualitative and
      quantitative evidence to support a high fidelity simulated model of teaching
      clinical skills development for first year undergraduate nursing students. High
      positive scores in all sections of the student survey provide quantitative
      evidence of student's satisfaction with all elements of the teaching model and
      qualitative data from interviews supporting this claim. Additionally, analysis of
      interview data provides qualitative evidence to support the value of the learning
      experience for students and academics, and students desire to participate more
      frequently in simulation sessions. 

PMID- 23880301
TI  - [Brain calcifications].

PMID- 23880302
TI  - Structural and functional insights on folate receptor alpha (FRalpha) by homology
      modeling, ligand docking and molecular dynamics.
AB  - Folate receptor alpha (FRalpha) is a cell surface, glycophosphatidylinositol
      (GPI)-anchored protein with a high affinity for its ligand partner, which is
      highly expressed in malignant cells and has been selected as a therapeutic target
      and marker for the diagnosis of cancer. No direct structural information is
      available from either X-ray diffraction or NMR on the post-translational
      structure of this disulfide-rich protein. Three-dimensional models of the FRalpha
      structure have been derived with the recent homology modeling packages, using the
      crystal structure of the riboflavin-binding protein (RfBP) as a template.
      Molecular dynamics trajectories have been exploited allowing successfully the
      formation of a full disulfide bridge network, which was expected based on the
      similarities between FRalpha and RfBP. After the selection of the best model, a
      folic acid molecule was docked "in silico" onto the putative binding site and its
      binding mode was compared with that of vintafolide, a much larger molecule
      designed as a chemotherapy agent targeting specifically FRalpha. In both cases, a
      40ns molecular dynamics trajectory was calculated, providing suggestions
      regarding the key structural determinants driving the affinity and specificity of
      FRalpha for folic acid with respect to other folate homologues. Moreover, some
      other crucial experimental results related to the structure of the receptor are
      discussed, such as the expected location/accessibility of known immune epitopes,
      the set of N-linked glycosylation sites and the effect of point mutations on the
      impairment of folate binding. Our results may provide useful insights for studies
      related to folate-targeted drug delivery or cancer therapies involving folate
      uptake. 

PMID- 23880303
TI  - Fibroblast growth factor receptors, developmental corruption and malignant
      disease.
AB  - Fibroblast growth factors (FGF) are a family of ligands that bind to four
      different types of cell surface receptor entitled, FGFR1, FGFR2, FGFR3 and FGFR4.
      These receptors differ in their ligand binding affinity and tissue distribution.
      The prototypical receptor structure is that of an extracellular region comprising
      three immunoglobulin (Ig)-like domains, a hydrophobic transmembrane segment and a
      split intracellular tyrosine kinase domain. Alternative gene splicing affecting
      the extracellular third Ig loop also creates different receptor isoforms entitled
      FGFRIIIb and FGFRIIIc. Somatic fibroblast growth factor receptor (FGFR) mutations
      are implicated in different types of cancer and germline FGFR mutations occur in
      developmental syndromes particularly those in which craniosynostosis is a
      feature. The mutations found in both conditions are often identical. Many somatic
      FGFR mutations in cancer are gain-of-function mutations of established
      preclinical oncogenic potential. Gene amplification can also occur with 19-22% of
      squamous cell lung cancers for example having amplification of FGFR1. Ontologic
      comparators can be informative such as aberrant spermatogenesis being implicated
      in both spermatocytic seminomas and Apert syndrome. The former arises from
      somatic FGFR3 mutations and Apert syndrome arises from germline FGFR2 mutations.
      Finally, therapeutics directed at inhibiting the FGF/FGFR interaction are a
      promising subject for clinical trials. 

PMID- 23880304
TI  - Trichostatin-A modulates claudin-1 mRNA stability through the modulation of Hu
      antigen R and tristetraprolin in colon cancer cells.
AB  - Expression of claudin-1, a tight junction protein, is highly upregulated in colon
      cancer. We have reported that claudin-1 expression in colon cancer cells is
      epigenetically regulated as histone deacetylase (HDAC) inhibitors decrease
      claudin-1 messenger RNA (mRNA) stability and thus expression. In this regard, our
      data suggested a role of the 3'-untranslated region (UTR) in the regulation of
      HDAC-dependent regulation of claudin-1 mRNA stability. In the current study, we
      demonstrate, based on our continued investigation, that the ELAV-like RNA-binding
      proteins (RBPs), human antigen R (HuR) and tristetraprolin (TTP) associate with
      the 3'-UTR of claudin-1 mRNA to modulate the latter's stability. Ribonomic and
      site-directed mutagenesis approaches were used to confirm the binding of HuR and
      TTP to the 3'-UTR of claudin-1. We further confirmed their roles in the
      stabilization of claudin-1 mRNA, under conditions of HDAC inhibition. In summary,
      we report that HuR and TTP are the critical regulators of the posttranscriptional
      regulation of claudin-1 expression in colon cancer cells. We also demonstrate
      that inhibition of HDACs by trichostatin treatment decreased the binding of HuR
      while increasing the binding of TTP to the 3'-UTR of claudin-1. Additionally, we
      provide data showing transcriptional regulation of claudin-1 expression, through
      the regulation of transcription factor Sp1. Taken together, we demonstrate
      epigenetic regulation of claudin-1 expression in colon cancer cells at the
      transcriptional and posttranscriptional levels. 

PMID- 23880305
TI  - A sesquiterpene lactone antrocin from Antrodia camphorata negatively modulates
      JAK2/STAT3 signaling via microRNA let-7c and induces apoptosis in lung cancer
      cells.
AB  - Lung cancer is the leading cause of cancer deaths worldwide and current therapies
      fail to treat this disease in majority of cases. Antrodia camphorata is a
      medicinal mushroom being widely used as food dietary supplement for cancer
      prevention. The sesquiterpene lactone antrocin is the most potent among >100
      secondary metabolites isolated from A. camphorata. However, the molecular
      mechanisms of antrocin-mediated anticancer effects remain unclear. In this study,
      we found that antrocin inhibited cell proliferation in two non-small-cell lung
      cancer cells, namely H441 (wild-type epidermal growth factor receptor, IC50 =
      0.75 MUM) and H1975 (gefitnib-resistant mutant T790M, IC50 = 0.83 MUM). Antrocin
      dose dependently suppressed colony formation and induced apoptosis as evidenced
      by activated caspase-3 and increased Bax/Bcl2 ratio. Gene profiling studies
      indicated that antrocin downregulated Janus kinase/signal transducer and
      activator of transcription (JAK/STAT) signaling pathway. We further demonstrated
      that antrocin suppressed both constitutively activated and interleukin 6-induced
      STAT3 phosphorylation and its subsequent nuclear translocation. Such inhibition
      is found to be achieved through the suppression of JAK2 and interaction between
      STAT3 and extracellular signal-regulated kinase. Additionally, antrocin increased
      microRNA let-7c expression and suppressed STAT signaling. The combination of
      antrocin and JAK2/STAT3 gene silencing significantly increased apoptosis in H441
      cells. Such dual interruption of JAK2 and STAT3 pathways also induced
      downregulation of antiapoptotic protein mcl-1 and increased caspase-3 expression.
      In vivo intraperitoneal administration of antrocin significantly suppressed the
      growth of lung cancer tumor xenografts. Our results indicate that antrocin may be
      a potential therapeutic agent for human lung cancer cells through constitutive
      inhibition of JAK2/STAT3 pathway. 

PMID- 23880307
TI  - Seizure recurrence in patients with solitary cystic granuloma or single
      parenchymal cerebral calcification: a comparative evaluation.
AB  - BACKGROUND: Solitary cysticercus granuloma and single parenchymal calcified
      lesion are two common neuroimaging abnormalities in Indian patients with
      epilepsy. In this study, we evaluated the frequency and predictors of seizure
      recurrence in patients presenting with new onset epilepsy or single epileptic
      seizures and these two different imaging findings. MATERIALS AND METHODS: We
      enrolled 115 patients with newly diagnosed epilepsy. All patients were clinically
      evaluated and were treated with oxcarbazepine. No anti-helminthic treatment was
      prescribed. The patients were followed up for 6 months. In the solitary cystic
      granuloma group, repeat computed tomography was done after 6 months. RESULTS: The
      study included 80 patients with solitary cysticercus granuloma and 35 patients
      with a single calcified lesion. Twenty (25%) patients with solitary cysticercus
      granuloma and 12 (34.3%) patients with parenchymal calcified lesion had a seizure
      recurrence during the study period (p = 0.307). After 6 months, 57 (71.3%)
      patients in the solitary cysticercus granuloma group demonstrated complete
      resolution of the granuloma and in 21 (26.2%) patients the granuloma transformed
      into a calcified lesion. In the solitary cysticercus granuloma group, a family
      history of seizure, serial seizures and calcification on follow-up neuroimaging
      (p < 0.05) were significantly associated with recurrence of seizures. In patients
      with a single parenchymal calcified lesions, electroencephalographic
      abnormalities and serial seizures (p = < 0.05) were significant predictors of
      recurrence. Kaplan-Meier statistics revealed that the seizure recurrence rate was
      insignificantly higher in patients with calcified lesions than in patients with
      solitary cysticercosis granulomas. CONCLUSION: In conclusion, in patients with
      solitary cysticercus granuloma, a family history of seizures, serial seizures and
      calcification of the granuloma, and in patients with a calcified brain lesion,
      electroencephalographic abnormalities, family history of epilepsy and serial
      seizures were associated with an increased risk of seizure recurrence.

PMID- 23880306
TI  - Evaluation of the impact of immediate versus WHO recommendations-guided
      antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP
      (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South
      Africa: study protocol for a cluster randomised controlled trial.
AB  - BACKGROUND: Antiretroviral therapy (ART) suppresses HIV viral load in all body
      compartments and so limits the risk of HIV transmission. It has been suggested
      that ART not only contributes to preventing transmission at individual but
      potentially also at population level. This trial aims to evaluate the effect of
      ART initiated immediately after identification/diagnosis of HIV-infected
      individuals, regardless of CD4 count, on HIV incidence in the surrounding
      population. The primary outcome of the overall trial will be HIV incidence over
      two years. Secondary outcomes will include i) socio-behavioural outcomes
      (acceptability of repeat HIV counselling and testing, treatment acceptance and
      linkage to care, sexual partnerships and quality of life); ii) clinical outcomes
      (mortality and morbidity, retention into care, adherence to ART, virologic
      failure and acquired HIV drug resistance), iii) cost-effectiveness of the
      intervention. The first phase will specifically focus on the trial's secondary
      outcomes. METHODS/DESIGN: A cluster-randomised trial in 34 (2 * 17) clusters
      within a rural area of northern KwaZulu-Natal (South Africa), covering a total
      population of 34,000 inhabitants aged 16 years and above, of whom an estimated
      27,200 would be HIV-uninfected at start of the trial. The first phase of the
      trial will include ten (2 * 5) clusters. Consecutive rounds of home-based HIV
      testing will be carried out. HIV-infected participants will be followed in
      dedicated trial clinics: in intervention clusters, they will be offered immediate
      ART initiation regardless of CD4 count and clinical stage; in control clusters
      they will be offered ART according to national treatment eligibility guidelines
      (CD4 <350 cells/MUL, World Health Organisation stage 3 or 4 disease or multidrug
      resistant/extensively drug-resistant tuberculosis). Following proof of
      acceptability and feasibility from the first phase, the trial will be rolled out
      to further clusters. DISCUSSION: We aim to provide proof-of-principle evidence
      regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence
      at the population level. Data collected from the participants at home and in the
      clinics will inform understanding of socio-behavioural, economic and clinical
      impacts of the intervention as well as feasibility and generalizability. TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH
      27-0512-3974.

PMID- 23880308
TI  - The new allelic variant of the subtilase cytotoxin (subAB2) is common among Shiga
      toxin-producing Escherichia coli strains from large game animals and their meat
      and meat products.
AB  - Subtilase cytotoxin (SubAB) is an AB5 toxin produced by Shiga toxin (Stx)
      producing Escherichia coli (STEC) strains usually lacking the eae gene product
      intimin. Two allelic variants of SubAB encoding genes have been described:
      subAB1, located on a plasmid, and subAB2, located on a pathogenicity island (PAI)
      together with tia gene. While subAB1 has been reported to be more frequent among
      bovine strains, subAB2 has been mainly associated with strains from small
      ruminants. We investigated the presence of the two variants of subAB among 59 eae
      negative STEC from large game animals (deer and wild boar) and their meat and
      meat products in order to assess the role of other species in the epidemiology of
      subAB-positive, eae-negative STEC. For this approach, the strains were PCR
      screened for the presence of subAB, including the specific detection of both
      allelic variants, for the presence of saa, tia and sab, and for stx subtyping.
      Overall, subAB genes were detected in 71.2% of the strains: 84.1% of the strains
      from deer and 33.3% of the strains from wild boar. Most of them (97.6%) possessed
      subAB2 and most of these subAB2-positive strains (92.7%) were also positive for
      tia and negative for saa, suggesting the presence of the subAB2-harbouring PAI.
      Subtype stx2b was present in most of the strains (67.8%) and a statistically
      significant association could be established between subAB2 and stx2b. Our
      results suggest that large game animals, mainly deer, may represent an important
      animal reservoir of subAB2-positive, eae-negative STEC, and also highlight the
      risk of human infection posed by the consumption of large game meat and meat
      products. 

PMID- 23880309
TI  - Bach1 deficiency protects pancreatic beta-cells from oxidative stress injury.
AB  - BTB and CNC homology 1 (Bach1) is a transcriptional repressor of antioxidative
      enzymes, such as heme oxygenase-1 (HO-1). Oxidative stress is reportedly involved
      in insulin secretion impairment and obesity-associated insulin resistance.
      However, the role of Bach1 in the development of diabetes is unclear. HO-1
      expression in the liver, white adipose tissue, and pancreatic islets was markedly
      upregulated in Bach1-deficient mice. Unexpectedly, glucose and insulin tolerance
      tests showed no differences in obese wild-type (WT) and obese Bach1-deficient
      mice after high-fat diet loading for 6 wk, suggesting minimal roles of Bach1 in
      the development of insulin resistance. In contrast, Bach1 deficiency
      significantly suppressed alloxan-induced pancreatic insulin content reduction and
      the resultant glucose elevation. Furthermore, TUNEL-positive cells in pancreatic
      islets of Bach1-deficient mice were markedly decreased, by 60%, compared with
      those in WT mice. HO-1 expression in islets was significantly upregulated in
      alloxan-injected Bach1-deficient mice, whereas expression of other antioxidative
      enzymes, e.g., catalase, superoxide dismutase, and glutathione peroxidase, was
      not changed by either alloxan administration or Bach1 deficiency. Our results
      suggest that Bach1 deficiency protects pancreatic beta-cells from oxidative
      stress-induced apoptosis and that the enhancement of HO-1 expression plays an
      important role in this protection.

PMID- 23880310
TI  - Excess TSH causes abnormal skeletal development in young mice with hypothyroidism
      via suppressive effects on the growth plate.
AB  - Hypothyroidism in the young leads to irreversible growth failure. hyt/hyt Mice
      have a nonfunctional TSH receptor (TSHR) and are severely hypothyroid, but growth
      retardation was not observed in adult mice. We found that epiphysial cartilage as
      well as cultured chondrocytes expressed functional TSHR at levels comparable to
      that seen in the thyroid, and that addition of TSH to cultured chondrocytes
      suppressed expression of chondrocyte differentiation marker genes such as Sox-9
      and type IIa collagen. Next, we compared the long bone phenotypes of two distinct
      mouse models of hypothyroidism: thyroidectomized (THYx) mice and hyt/hyt mice.
      Although both THYx and hyt/hyt mice were severely hypothyroid and had similar
      serum Ca(2+) and growth hormone levels, the tibia was shorter and the
      proliferating and hypertrophic zones in the growth plate was significantly
      narrower in THYx mice than in hyt/hyt mice. Supplementation of hyt/hyt mice
      thyroid hormone resulted in a wider growth plate compared with that of wild-type
      mice. Expressions of chondrocyte differentiation marker genes Sox-9 and type IIa
      collagen in growth plate from THYx mice were 52 and 60% lower than those of
      hyt/hyt mice, respectively. High serum TSH causes abnormal skeletal development
      in young mice with hypothyroidism via suppressive effects on the growth plate.

PMID- 23880311
TI  - Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin
      and leptin signaling in obese rats.
AB  - Hypothalamic inflammation is associated with insulin and leptin resistance,
      hyperphagia, and obesity. In this scenario, hypothalamic protein tyrosine
      phosphatase 1B (PTP1B) has emerged as the key phosphatase induced by inflammation
      that is responsible for the central insulin and leptin resistance. Here, we
      demonstrated that acute exercise reduced inflammation and PTP1B protein
      level/activity in the hypothalamus of obese rodents. Exercise disrupted the
      interaction between PTP1B with proteins involved in the early steps of insulin
      (IRbeta and IRS-1) and leptin (JAK2) signaling, increased the tyrosine
      phosphorylation of these molecules, and restored the anorexigenic effects of
      insulin and leptin in obese rats. Interestingly, the anti-inflammatory action and
      the reduction of PTP1B activity mediated by exercise occurred in an interleukin-6
      (IL-6)-dependent manner because exercise failed to reduce inflammation and PTP1B
      protein level after the disruption of hypothalamic-specific IL-6 action in obese
      rats. Conversely, intracerebroventricular administration of recombinant IL-6
      reproduced the effects of exercise, improving hypothalamic insulin and leptin
      action by reducing the inflammatory signaling and PTP1B activity in obese rats at
      rest. Taken together, our study reports that physical exercise restores insulin
      and leptin signaling, at least in part, by reducing hypothalamic PTP1B protein
      level through the central anti-inflammatory response.

PMID- 23880312
TI  - Trehalose prevents neural tube defects by correcting maternal diabetes-suppressed
      autophagy and neurogenesis.
AB  - Preexisting maternal diabetes increases the risk of neural tube defects (NTDs).
      The mechanism underlying maternal diabetes-induced NTDs is not totally defined,
      and its prevention remains a challenge. Autophagy, an intracellular process to
      degrade dysfunction protein and damaged cellular organelles, regulates cell
      proliferation, differentiation, and apoptosis. Because autophagy impairment
      causes NTDs reminiscent of those observed in diabetic pregnancies, we hypothesize
      that maternal diabetes-induced autophagy impairment causes NTD formation by
      disrupting cellular homeostasis, leading to endoplasmic reticulum (ER) stress and
      apoptosis, and that restoration of autophagy by trehalose, a natural
      disaccharide, prevents diabetes-induced NTDs. Embryos from nondiabetic and type 1
      diabetic mice fed with or without 2 or 5% trehalose water were used to assess
      markers of autophagy, ER stress, and neurogenesis, numbers of autophagosomes,
      gene expression that regulates autophagy, NTD rates, indices of mitochondrial
      dysfunction, and neuroepithelial cell apoptosis. Maternal diabetes suppressed
      autophagy by significantly reducing LC3-II expression, autophagosome numbers, and
      GFP-LC3 punctate foci in neuroepithelial cells and by altering autophagy-related
      gene expression. Maternal diabetes delayed neurogenesis by blocking Sox1 neural
      progenitor differentiation. Trehalose treatment reversed autophagy impairment and
      prevented NTDs in diabetic pregnancies. Trehalose resolved homeostatic imbalance
      by correcting mitochondrial defects, dysfunctional proteins, ER stress,
      apoptosis, and delayed neurogenesis in the neural tubes exposed to hyperglycemia.
      Our study demonstrates for the first time that maternal diabetes suppresses
      autophagy in neuroepithelial cells of the developing neural tube, leading to NTD
      formation, and provides evidence for the potential efficacy of trehalose as an
      intervention against hyperglycemia-induced NTDs.

PMID- 23880314
TI  - Dietary protein decreases exercise endurance through rapamycin-sensitive
      suppression of muscle mitochondria.
AB  - Loss of physical performance is linked not only to decreased activity in daily
      life but also to increased onset of cardiovascular diseases and mortality. A high
      protein diet is recommended for aged individuals in order to preserve muscle
      mass; however, the regulation of muscle mitochondria by dietary protein has not
      been clarified. We investigated the long-term effects of a high-protein diet on
      muscle properties, focusing especially on muscle mitochondria. Mice were fed a
      high-protein diet from the age of 8 wk and examined for mitochondrial properties
      and exercise endurance at the ages of 20 and 50 wk. Compared with normal chow, a
      high-protein diet significantly decreased the amount of muscle mitochondria,
      mitochondrial activity, and running distance at 50 wk, although it increased
      muscle mass and grip power. Inhibition of TORC1-dependent signal pathways by
      rapamycin from 8 wk suppressed the decline in mitochondria and exercise endurance
      observed when mice were fed the high-protein diet in association with preserved
      AMPK activity. Collectively, these findings suggest a role for dietary protein as
      a suppressor of muscle mitochondria and indicate that the age-associated decline
      in exercise endurance might be accelerated by excessive dietary protein through
      rapamycin-sensitive suppression of muscle mitochondria.

PMID- 23880313
TI  - p-FAK-Tyr(397) regulates spermatid adhesion in the rat testis via its effects on
      F-actin organization at the ectoplasmic specialization.
AB  - During spermatogenesis, the molecular mechanism that confers spermatid adhesion
      to the Sertoli cell at the apical ectoplasmic specialization (apical ES), a
      testis-specific F-actin-rich adherens junction, in the rat testis remains
      elusive. Herein, the activated form of focal adhesion kinase (FAK), p-FAK
      Tyr(397), a component of the apical ES that was expressed predominantly and stage
      specifically in stage VII-early stage VIII tubules, was found to be a crucial
      apical ES regulator. Using an FAK-Y397E phosphomimetic mutant cloned in a
      mammalian expression vector for its transfection vs. FAK and vector alone in
      adult rat testes in vivo, its overexpression was found to cause defects in
      spermiation. These defects in spermiation were manifested by entrapment of
      spermatids in the seminiferous epithelium in late stage VIII-X tubules and were
      mediated by a disruption on the spatiotemporal expression and/or mislocalization
      of actin regulatory protein actin-related protein 3, which induces branched actin
      polymerization, epidermal growth factor receptor pathway substrate 8 (an actin
      barbed end capping and bundling protein), and palladin (an actin cross-linking
      and bundling protein). This thus perturbed changes of F-actin organization at the
      apical ES to facilitate spermiation, which also led to a concomitant alteration
      in the distribution and upregulation of adhesion proteins nectin-2 and nectin-3
      at the apical ES. As such, nectin-2 and -3 remained at the apical ES to anchor
      step 19 spermatids on to the epithelium, delaying spermiation. These findings
      illustrate a mechanistic pathway mediated by p-FAK-Tyr(397) that regulates
      spermatid adhesion at the apical ES in vivo.

PMID- 23880315
TI  - Metallothionein-I- and -II-deficient mice display increased susceptibility to
      cadmium-induced fetal growth restriction.
AB  - Maternal cadmium exposure induces fetal growth restriction (FGR), but the
      underlying mechanisms remain largely unknown. The placenta is the main organ
      known to protect the fetus from environmental toxins such as cadmium. In this
      study, we examine the role of the two key placental factors in cadmium-induced
      FGR. The first is placental enzyme 11beta-hydroxysteroid dehydrogenase type 2
      (11beta-HSD2), which is known to protect the fetus from exposure to high cortisol
      levels and subsequently FGR, and the second the cadmium binding/sequestering
      proteins metallotheionein (MT)-I and -II. Using the MT-I/II(-/-) mouse model,
      pregnant mice were administered cadmium, following which pups and placentas were
      collected and examined. MT-I/II(-/-) pups exposed to cadmium were significantly
      growth restricted, but neither placental weight nor 11beta-HSD2 was altered.
      Although cadmium administration did not result in any visible structural changes
      in the placenta, increased apoptosis was detected in MT-I/II(-/-) placentas
      following cadmium exposure, with a significant increase in levels of both p53 and
      caspase 3 proteins. Additionally, glucose transporter (GLUT1) was significantly
      reduced in MT-I/II(-/-) placentas of pups exposed to cadmium, whereas zinc
      transporter (ZnT-1) remained unaltered. Taken together, these results demonstrate
      that MT-I/II(-/-) mice are more vulnerable to cadmium-induced FGR. The present
      data also suggest that increased apoptosis and reduced GLUT1 expression in the
      placenta contribute to the molecular mechanisms underlying cadmium-induced FGR.

PMID- 23880317
TI  - Characterizing the neuroendocrine and ovarian defects of androgen receptor
      knockout female mice.
AB  - Homozygous androgen receptor (AR)-knockout (ARKO) female mice are subfertile due
      to both intra- and extraovarian (neuroendocrine) defects as defined by ovary
      transplantation. Using ARKO mice, this study set out to reveal the precise AR
      regulated pathways required for optimal androgen-regulated ovulation and
      fertility. ARKO females exhibit deficient neuroendocrine negative feedback, with
      a reduced serum luteinizing hormone (LH) response to ovariectomy (OVX) (P <
      0.01). Positive feedback is also altered as intact ARKO females, at late
      proestrus, exhibit an often mistimed endogenous ovulatory LH surge. Furthermore,
      at late proestrus, intact ARKO females display diminished preovulatory serum
      estradiol (E2; P < 0.01) and LH (P < 0.05) surge levels and reduced Kiss1 mRNA
      expression in the anteroventral periventricular nucleus (P < 0.01) compared with
      controls. However, this reduced ovulatory LH response in intact ARKO females can
      be rescued by OVX and E2 priming or treatment with endogenous GnRH. These
      findings reveal that AR regulates the negative feedback response to E2, E2
      positive feedback is compromised in ARKO mice, and AR-regulated negative and
      positive steroidal feedback pathways impact on intrahypothalamic control of the
      kisspeptin/GnRH/LH cascade. In addition, intraovarian AR-regulated pathways
      controlling antral to preovulatory follicle dynamics are disrupted because adult
      ARKO ovaries collected at proestrus have small antral follicles with reduced
      oocyte/follicle diameter ratios (P < 0.01) and increased proportions of unhealthy
      large antral follicles (P < 0.05) compared with controls. As a consequence of
      aberrant follicular growth patterns, proestrus ARKO ovaries also exhibit fewer
      preovulatory follicle (P < 0.05) and corpora lutea numbers (P < 0.01). However,
      embryo development to the blastocyst stage is unchanged in ARKO females, and
      hence, the subfertility is a consequence of reduced ovulations and not altered
      embryo quality. These findings reveal that the AR has a functional role in
      neuroendocrine regulation and timing of the ovulatory LH surge as well as
      antral/preovulatory follicle development.

PMID- 23880316
TI  - Regulation of lipid synthesis genes and milk fat production in human mammary
      epithelial cells during secretory activation.
AB  - Expression of genes for lipid biosynthetic enzymes during initiation of lactation
      in humans is unknown. Our goal was to study mRNA expression of lipid metabolic
      enzymes in human mammary epithelial cell (MEC) in conjunction with the
      measurement of milk fatty acid (FA) composition during secretory activation. Gene
      expression from mRNA isolated from milk fat globule (MFG) and milk FA composition
      were measured from 6 h to 42 days postpartum in seven normal women. Over the
      first 96 h postpartum, daily milk fat output increased severalfold and mirrored
      expression of genes for all aspects of lipid metabolism and milk FA production,
      including lipolysis at the MEC membrane, FA uptake from blood, intracellular FA
      transport, de novo FA synthesis, FA and glycerol activation, FA elongation, FA
      desaturation, triglyceride synthesis, cholesterol synthesis, and lipid droplet
      formation. Expression of the gene for a key lipid synthesis regulator, sterol
      regulatory element-binding transcription factor 1 (SREBF1), increased 2.0-fold by
      36 h and remained elevated over the study duration. Expression of genes for
      estrogen receptor 1, thyroid hormone-responsive protein, and insulin-induced 2
      increased progressively to plateau by 96 h. In contrast, mRNA of peroxisome
      proliferator-activated receptor-gamma decreased severalfold. With onset of
      lactation, increased de novo synthesis of FA was the most prominent change in
      milk FA composition and mirrored the expression of FA synthesis genes. In
      conclusion, milk lipid synthesis and secretion in humans is a complex process
      requiring the orchestration of a wide variety of pathways of which SREBF1 may
      play a primary role.

PMID- 23880318
TI  - Analysis of the fate and transport of nC60 nanoparticles in the subsurface using
      response surface methodology.
AB  - Predicting the distribution of engineered nanomaterials (ENMs) in the environment
      will provide critical information for risk assessment and policy development to
      regulate these emerging contaminants. The fate and transport of ENMs in natural
      subsurface environments are complicated by various factors, such as hydraulic
      gradient, initial release concentration, nanoparticle size, and collision
      efficiency factor. Based on advanced statistical methodologies (i.e., response
      surface methodology (RSM)), we explore simple relationships between key factors
      that control ENM transport (collision efficiency factor, particle size, hydraulic
      gradient, and initial release concentration) and key parameters that describe the
      ENM concentration distribution in porous media (maximum standardized
      concentration, the mass percentage of injected nanoparticle attached in the
      aquifer, the x-centroid of aqueous phase nC60 plume, and the x-centroid of
      attached phase nC60 distribution). Hypothetical scenarios for the release of
      nanoparticles into an aquifer were simulated numerically with randomly generated
      permeability fields that were based on mildly and highly heterogeneous sites. RSM
      was used to develop polynomial regression equations based on a statistical
      experimental design. High R-squared values (greater than 0.9) of the regression
      equations were obtained for all the models developed based on the mildly
      heterogeneous site. On the highly heterogeneous site, the R-squared value of the
      regression equation for the percentage of nanoparticles attached (by mass) was
      more than 0.9. The ability to accurately estimate aqueous phase ENM concentration
      distribution using simple regression equations is particularly critical for risk
      assessment. Even though the correlations developed in this study were site and
      scenario specific, this work represents a first effort of applying RSM for
      predicting the distribution of engineered nanomaterials in porous media.

PMID- 23880319
TI  - Development and evaluation of a computer adaptive test to assess anxiety in
      cardiovascular rehabilitation patients.
AB  - OBJECTIVE: To develop and evaluate a computer adaptive test for the assessment of
      anxiety in cardiovascular rehabilitation patients (ACAT-cardio) that tailors an
      optimal test for each patient and enables precise and time-effective measurement.
      DESIGN: Simulation study, validation study (against the anxiety subscale of the
      Hospital Anxiety and Depression Scale and the physical component summary scale of
      the 12-Item Short-Form Health Survey), and longitudinal study (beginning and end
      of rehabilitation). SETTING: Cardiac rehabilitation centers. PARTICIPANTS:
      Cardiovascular rehabilitation patients: simulation study sample (n=106; mean age,
      57.8y; 25.5% women) and validation and longitudinal study sample (n=138; mean
      age, 58.6 and 57.9y, respectively; 16.7% and 12.1% women, respectively).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Hospital Anxiety and
      Depression Scale, 12-Item Short-Form Health Survey, and ACAT-cardio. RESULTS: The
      mean number of items was 9.2 with an average processing time of 1:13 minutes when
      an SE <=.50 was used as a stopping rule; with an SE <=.32, there were 28 items
      and a processing time of 3:47 minutes. Validity could be confirmed via
      correlations between .68 and .81 concerning convergent validity (ACAT-cardio vs
      Hospital Anxiety and Depression Scale anxiety subscale) and correlations between 
      .47 and -.30 concerning discriminant validity (ACAT-cardio vs 12-Item Short-Form
      Health Survey physical component summary scale). Sensitivity to change was
      moderate to high with standardized response means between .45 and .82.
      CONCLUSIONS: The ACAT-cardio shows good psychometric properties and provides the
      opportunity for an innovative and time-effective assessment of anxiety in
      cardiovascular rehabilitation. A more flexible stopping rule might further
      improve the ACAT-cardio. Additionally, testing in other cardiovascular
      populations would increase generalizability.

PMID- 23880320
TI  - Differential activity of c-KIT splice forms is controlled by extracellular
      peptide insert length.
AB  - Understanding receptor activation is important for disease intervention.
      Activation of the receptor tyrosine kinase c-KIT is involved in numerous diseases
      including melanoma, mastocytosis, multiple myeloma and gastrointestinal stromal
      tumors. To better understand the regulation of activation, we studied the two c
      KIT isoforms, c-KIT(-) and c-KIT(+), which differ by a tetrapeptide insert GNNK,
      located in the extracellular juxtamembrane domain of the c-KIT(+) isoform. This
      region is important for regulating receptor activation. Here we show that the
      consecutive elimination of one amino acid at a time from the GNNK tetrapeptide
      insert gradually increases receptor tyrosine phosphorylation, ubiquitination,
      internalization and downstream MAP kinase-ERK activation. Successively decreasing
      the insert length progressively improves cell survival during drug treatment. Our
      results indicate that the length of the tetrapeptide fine-tunes receptor
      activity, thus providing deeper insight into c-KIT activation. 

PMID- 23880321
TI  - Flat-panel volumetric computed tomography in cerebral perfusion: evaluation of
      three rat stroke models.
AB  - Flat-panel volumetric computed tomography (fpVCT) is a non-invasive approach to
      three-dimensional small animal imaging. The capability of volumetric scanning and
      a high resolution in time and space enables whole organ perfusion studies. We
      aimed to assess feasibility and validity of fpVCT in cerebral perfusion
      measurement with impaired hemodynamics by evaluation of three well-established
      rat stroke models for temporary and permanent middle cerebral artery occlusion
      (MCAO). Male Wistar rats were randomly assigned to temporary (group I: suture
      model) and permanent (group II: suture model; III: macrosphere model) MCAO and to
      a control group. Perfusion scans with respect to cerebral blood flow (CBF) and
      volume (CBV) were performed 24h post intervention by fpVCT, using a Gantry
      rotation time of 1s and a total scanning time of 30s. Postmortem analysis
      included infarct-size calculation by 2,3,5-triphenyltetrazolium chloride (TTC)
      staining. Infarct volumes did not differ significantly throughout intervention
      groups. After permanent MCAO, CBF significantly decreased in subcortical regions
      to 78.2% (group II, p=0.005) and 79.9% (group III, p=0.012) and in total
      hemisphere to 77.4% (group II, p=0.010) and 82.0% (group III, p=0.049). CBF was
      less impaired with temporary vessel occlusion. CBV measurement revealed no
      significant differences. Results demonstrate feasibility of cerebral perfusion
      quantification in rats with the fpVCT, which can be a useful tool for non
      invasive dynamic imaging of cerebral perfusion in rodent stroke models. In
      addition to methodological advantages, CBF data confirm the macrosphere model as
      a useful alternative to the suture model for permanent experimental MCAO. 

PMID- 23880322
TI  - Genome-enabled methods for predicting litter size in pigs: a comparison.
AB  - Predictive ability of models for litter size in swine on the basis of different
      sources of genetic information was investigated. Data represented average litter
      size on 2598, 1604 and 1897 60K genotyped sows from two purebred and one
      crossbred line, respectively. The average correlation (r) between observed and
      predicted phenotypes in a 10-fold cross-validation was used to assess predictive
      ability. Models were: pedigree-based mixed-effects model (PED), Bayesian ridge
      regression (BRR), Bayesian LASSO (BL), genomic BLUP (GBLUP), reproducing kernel
      Hilbert spaces regression (RKHS), Bayesian regularized neural networks (BRNN) and
      radial basis function neural networks (RBFNN). BRR and BL used the marker matrix
      or its principal component scores matrix (UD) as covariates; RKHS employed a
      Gaussian kernel with additive codes for markers whereas neural networks employed
      the additive genomic relationship matrix (G) or UD as inputs. The non-parametric
      models (RKHS, BRNN, RNFNN) gave similar predictions to the parametric
      counterparts (average r ranged from 0.15 to 0.23); most of the genome-based
      models outperformed PED (r = 0.16). Predictive abilities of linear models and
      RKHS were similar over lines, but BRNN varied markedly, giving the best
      prediction (r = 0.31) when G was used in crossbreds, but the worst (r = 0.02)
      when the G matrix was used in one of the purebred lines. The r values for RBFNN
      ranged from 0.16 to 0.23. Predictive ability was better in crossbreds (0.26) than
      in purebreds (0.15 to 0.22). This may be related to family structure in the
      purebred lines. 

PMID- 23880323
TI  - Impact of plasma treatment of PMMA-based CAD/CAM blanks on surface properties as
      well as on adhesion to self-adhesive resin composite cements.
AB  - OBJECTIVES: To test surface energy, roughness and tensile bond strength (TBS) to
      self-adhesive resin composite cements without/with plasma treatment combined with
      different conditioning methods of PMMA-based CAD/CAM blocks. METHODS: PMMA
      specimens (10mm*10mm*2mm) were fabricated (N=260), polished and air-abraded
      (50MUm Al2O3, 5s, 0.05MPa). Twenty specimens were selected for surface energy and
      roughness measurements (without/with plasma n=10 per group). The remaining
      specimens (n=240) were used for TBS testing without/with plasma treatment and
      following conditioning methods (n=20 per test group): (i) without conditioning,
      (ii) Visio.link, (iii) VP connect and luted with Clearfil SA Cement and RelyX
      Unicem Automix. Specimens were aged (24h 37 degrees C water+5000 thermal cycles,
      5 degrees C/55 degrees C), TBS was measured and failure types were assessed. Data
      were analyzed using descriptive statistics, Mann-Whitney-U and Kruskal-Wallis-H
      tests, unpaired t-test, Chi(2) and the Spearman correlation test. RESULTS: Plasma
      treatment of PMMA increased the surface energy significantly (p<0.001) but had no
      impact on the surface roughness (p=0.718). Groups without plasma treatment showed
      higher TBS than plasma treated groups (p<0.001 to p=0.011), except PMMA
      conditioned with VP connect and luted using RelyX Unicem Automix (p=0.03).
      Clearfil SA Cement showed higher TBS compared to RelyX Unicem Automix, except for
      groups conditioned with Visio.link. Both resin composite cements showed the
      highest TBS for groups conditioned with Visio.link. Also, among Clearfil SA
      Cement, conditioning with VP connect showed comparable TBS to Visio.link.
      SIGNIFICANCE: Plasma treatment of PMMA did not increase the adhesion to self
      adhesive resin composite cements.

PMID- 23880324
TI  - Educational preparation for clinical nursing: the satisfaction of students and
      new graduates from two Australian universities.
AB  - BACKGROUND: Attrition rates among young and newly registered nurses are high; the
      capacity of nurse education programmes to prepare nurses for their professional
      role and the extent to which they are supported during the transition from
      student to registered nurse may be important factors. OBJECTIVES: This paper
      examines nursing student and recent graduate satisfaction with their education,
      focusing on their preparation for work. DESIGN: A descriptive cohort design was
      used, combining qualitative and quantitative methods to measure and interpret
      satisfaction. SETTING: Two Australian universities, one urban and one regional.
      PARTICIPANTS: 530 undergraduate nursing students and recent graduates from the
      Bachelor of Nursing programmes at the two universities. METHODS: Data were
      collected via an online survey. Satisfaction with the programmes was measured
      with closed format questions covering different aspects of the programmes and a
      single open ended question. Responses were compared between older and younger
      respondents and between graduates and students at different stages of the
      programme. RESULTS: Older students were more dissatisfied than younger students
      with the amount and type of training and their preparation for nursing work.
      First year students reported the highest levels of satisfaction, and third year
      students the lowest. The majority of graduates and third year students thought
      that the programme only partly prepared them for work in nursing. The free text
      comments particularly highlighted concerns with the amount and quality of
      clinical education. CONCLUSIONS: Programmes need to take account of the learning
      requirements of students to maximise the integration of theory and skill
      development in hospital environments with limited staffing and resources. The
      clinical environment and support received impact on the quality of learning and
      satisfaction of student nurses. Students who are dissatisfied with their
      educational and clinical experiences may choose to change their career direction.

PMID- 23880325
TI  - The role of professional education in developing compassionate practitioners: a
      mixed methods study exploring the perceptions xof health professionals and pre
      registration students.
AB  - Compassionate practice is a public expectation and a core health professional
      value. However, in the face of growing public and professional unease about a
      perceived absence of compassion in health care it is essential that the role of
      education in developing compassionate practitioners is fully understood. The aim
      of this study was to explore qualified health professionals' and pre-registration
      students' understanding of compassion and the role of health professional
      education in promoting compassionate care. A sequential explanatory mixed methods
      study collected data using surveys and qualitative semi-structured interviews
      from qualified health professionals (n=155) and pre-registration students
      (n=197). Participants were from a range of health and social care disciplines and
      registered at a UK university. The findings indicate a high level of consensus in
      relation to participants' understanding of compassion in health care. Acting with
      warmth and empathy, providing individualised patient care and acting in a way you
      would like others to act towards you, were seen as the most common features of
      compassionate care. However, ambiguities and contradictions were evident when
      considering the role of health professional education in promoting compassionate
      practice. This study adds to the debate and current understanding of the role of
      education in fostering compassionate health care practice. 

PMID- 23880326
TI  - Adolescents and adults in pediatric urology clinics.
AB  - OBJECTIVE: Adolescents represent a significant proportion of the patients seen by
      pediatric urologists (PU). Adolescents that require long-term follow-up (FU)
      eventually need to be transferred to adult care. This research aims to describe
      the disease profile of adolescent and adult patients from a referral PU clinic,
      in order to allow future medical education and cost planning. PATIENTS AND
      METHODS: A retrospective review was made of cases seen in a PU referral clinic
      from January 1st to December 31st 2011. Patients were classified as child (<=12
      years old), adolescent (12 < age <= 18 years old) or adult (>18 years old).
      Diagnoses and presentations were analyzed. RESULTS: 521 patients were seen: 404
      children (77.5%), 103 adolescents (19.8%) and 14 adults (2.7%). Clinical profiles
      differed between the three groups. 43.7% of the adolescents and all adults were
      FU cases or patients with late sequelae of congenital diseases. Some diseases
      predominated largely in adolescents. CONCLUSIONS: Adolescents represent a
      significant proportion of our PU clinics. Half of them are FU cases or present
      sequelae from previous treatments/diseases. Some adolescents do not adapt to
      adult care, and persist being followed up by PU.

PMID- 23880327
TI  - Anti-secretory and cyto-protective effects of peganine hydrochloride isolated
      from the seeds of Peganum harmala on gastric ulcers.
AB  - Gastroprotective mechanism of peganine hydrochloride isolated from Peganum
      harmala seeds was investigated. Peganine hydrochloride was evaluated against cold
      restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced
      gastric ulcer models in rats. Potential anti-ulcer activity of peganine was
      observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced
      ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45%
      protection against CRU, 49.97% against AS and 69.42% against PL model.
      Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in
      AL induced ulcer model. Peganine significantly reduced free acidity (33.38%),
      total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively.
      Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with
      IC50 of 73.47MUg/ml as compared to the IC50 value of omeprazole (30.24MUg/ml)
      confirming its anti-secretory activity. 

PMID- 23880328
TI  - Protective effect of total phenylethanoid glycosides from Monochasma savatieri
      Franch on myocardial ischemia injury.
AB  - The present study was designed to investigate the cardioprotective effect of
      total phenylethanoid glycosides from Monochasma savatieri Franch (TPG). The data
      showed that there were mainly four phenylethanoid glycosides isolated and
      identified from TPG. TPG significantly increased cells viability and inhibited
      morphological changes on H9c2 cardiomyocytes induced by H2O2 or Na2S2O4. In
      addition, TPG significantly decreased T-wave elevation and histopathological
      changes of heart tissues in myocardial infracted rats induced by isoproterenol.
      It also significantly reduced the infarct size induced by ligating the coronary
      artery in rats, increased the activities of antioxidative enzymes superoxide
      dismutase (SOD), the content of glutathione (GSH), and decreased the leakage of
      lactic dehydrogenase (LDH), the activities of creatine kinase (CK) and the
      content of maleic dialdehyde (MDA). In conclusion, these results suggested that
      TPG from Monochasma savatieri Franch might be developed as new natural medicine
      or food additives with effects of prevention of coronary artery disease due to
      its significant antioxidant activity. 

PMID- 23880329
TI  - Antihypertensive and vasorelaxant effects of dihydrospinochalcone-A isolated from
      Lonchocarpus xuul Lundell by NO production: computational and ex vivo approaches.
AB  - Current work was conducted to evaluate the vasorelaxant effect of
      dihydrospinochalcone-A (1) and isocordoin (2), compounds type chalcone isolated
      from Lonchocarpus xuul, an endemic tree of the Yucatan Peninsula, Mexico.
      Compounds 1 and 2 were found to induce significant relaxant effect in a
      concentration-dependent manner on aortic rat rings pre-contracted with
      noradrenaline (NA, 0.1 MUM). Compound 1 was the most active and its effect was
      endothelium-dependent (Emax=79.67% and EC50=21.46 MUM with endothelium and
      Emax=23.58% and EC50=91.8 MUM without endothelium, respectively). The functional
      mechanism of action for 1 was elucidated. Pre-incubation with L-NAME (unspecific
      nitric oxide synthase inhibitor), indomethacin (unspecific COX inhibitor), ODQ
      (soluble guanylyl cyclase inhibitor), atropine (cholinergic receptor antagonist),
      TEA (unspecific potassium channel blocker) reduced relaxations induced by 1. Oral
      administration of 50 mg/kg of compound 1 exhibited significant decrease in
      diastolic and systolic blood pressure in SHR rats. The heart rate was not
      modified. Compound 1 was docked with a crystal structure of eNOS.
      Dihydrospinochalcone-A showed calculated affinity with eNOS in the C1 binding
      pockets, near the catalytic site; Trp449, Trp447 and His373 through aromatic and
      pi-pi interactions, also His463 and Arg367 are the residues that make hydrogen
      bonds with the carbonyl and hydroxyl groups. In conclusion, dihydrospinochalcone
      A induces a significant antihypertensive effect due to its direct vasorelaxant
      action on rat aorta rings, through NO/sCG/PKG pathway and potassium channel
      opening.

PMID- 23880330
TI  - Cyclopia maculata (honeybush tea) stimulates lipolysis in 3T3-L1 adipocytes.
AB  - We have previously, for the first time, demonstrated that hot water extracts of
      Cyclopia maculata and Cyclopia subternata, endemic South African plants that are
      consumed as herbal teas, inhibit adipogenesis in 3T3-L1 adipocytes. The aim of
      this study was to extend the anti-obesity investigations of these plants by
      quantifying lipolysis in mature 3T3-L1 adipocytes. Glycerol concentration in
      culture supernatants was used as a marker of adipocyte lipolysis. Isoproterenol,
      a beta-adrenergic agonist and a known lipolytic agent, was used as a positive
      control in our assays. Lipolysis was stimulated by all extracts, although
      statistical significance was noted for fermented (oxidised) C. maculata only. A
      concentration of 80MUg/ml of C. maculata extract induced maximal lipolysis (1.8
      fold, p<0.001). The increased lipolysis was accompanied by an increase in the
      expression of hormone sensitive lipase (1.6-fold, p<0.05) and perilipin (1.6
      fold, p<0.05). The plant extracts, at the concentration range assayed (0
      100MUg/ml), were not cytotoxic in terms of mitochondrial dehydrogenase and
      adenosine-5'-triphosphate activity. These results showed that C. maculata
      stimulates lipolysis in mature 3T3-L1 adipocytes, providing further support for
      the anti-obesity effects of Cyclopia spp. 

PMID- 23880331
TI  - Comprehensive chemical analysis of Schisandra chinensis by HPLC-DAD-MS combined
      with chemometrics.
AB  - The fruit of Schisandra chinensis, namely "Wuweizi" in China, is a well-known
      herbal medicine and health food. In this paper, an accurate and reliable high
      performance liquid chromatography coupled with diode array detection and mass
      spectrometry was developed for quality evaluation of Wuweizi. Nine lignans,
      including schisandrol A, schisandrol B, angeloylgomisin H, gomisin G,
      schisantherin A, schisanhenol, schisandrin A, schisandrin B, and schisandrin C
      were determined simultaneously in forty-three batches of Wuweizi samples
      collected from different localities. Thirty-six common peaks were unequivocally
      identified or tentatively assigned by comparing their mass spectrometric data
      with reference compounds, self-established compound library and published
      literatures. And the thirty-six common peaks were selected as characteristic
      peaks to assess the similarity of chromatographic fingerprinting of these Wuweizi
      samples. Moreover, hierarchical clustering analysis and principal components
      analysis were successfully applied to demonstrate the variability of these
      Wuweizi samples. The results indicated the content of nine investigated lignans
      varied greatly among the samples, and samples collected from different localities
      could be discriminated. Furthermore, schisandrol A, schisandrol B, schisandrin B,
      and schisandrin C were found to chemical marker for evaluating the quality of
      Wuweizi. 

PMID- 23880332
TI  - Is prophylactic administration of the anticonvulsants necessary in tramadol
      intoxicated patients after an initial seizure?

PMID- 23880333
TI  - A cognitive-behavioral intervention for emotion regulation in adults with high
      functioning autism spectrum disorders: study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Adults with high-functioning autism spectrum disorders (ASD) have
      difficulties in social communication; thus, these individuals have trouble
      understanding the mental states of others. Recent research also suggests that
      adults with ASD are unable to understand their own mental states, which could
      lead to difficulties in emotion-regulation. Some studies have reported the
      efficacy of cognitive-behavioral therapy (CBT) in improving emotion-regulation
      among children with ASD. The current study will investigate the efficacy of group
      based CBT for adults with ASD. METHODS/DESIGN: The study is a randomized,
      waitlist controlled, single-blinded trial. The participants will be 60 adults
      with ASD; 30 will be assigned to a CBT group and 30 to a waitlist control group.
      Primary outcome measures are the 20-item Toronto Alexithymia Scale, the Coping
      Inventory for Stressful Situations, the Motion Picture Mind-Reading task, and an
      ASD questionnaire. The secondary outcome measures are the Center for
      Epidemiological Studies Depression Scale, the World Health Organization Quality
      of Life Scale 26-item version, the Global Assessment of Functioning, State-trait
      Anxiety Inventory, Social Phobia and Anxiety Inventory, and Liebowitz Social
      Anxiety Scale. All will be administered during the pre- and post-intervention,
      and 12 week follow-up periods. The CBT group will receive group therapy over an 8
      week period (one session per week) with each session lasting approximately 100
      minutes. Group therapy will consist of four or five adults with ASD and two
      psychologists. We will be using visual materials for this program, mainly the
      Cognitive Affective Training kit. DISCUSSION: This trial will hopefully indicate
      the efficacy of group-based CBT for adults with high- functioning ASD. TRIAL
      REGISTRATION: This trial was registered in The University Hospital Medical
      Information Network Clinical Trials Registry No. UMIN000006236.

PMID- 23880334
TI  - Developing an in situ nanosuspension: a novel approach towards the efficient
      administration of poorly soluble drugs at the anterior eye.
AB  - With about 50-60 million cases in the US alone, dry eye disease represents a
      severe health care problem. Cyclosporin A (CsA) would be a potent candidate for a
      causal therapy. However, CsA is not sufficiently water soluble to be
      administrated via simple eye drops. We developed an in situ nanosuspension (INS)
      as a novel approach towards the administration of CsA to the cornea. It
      precipitates upon contact with the tear fluid and creates CsA nanoparticles that
      enter the cornea and release the drug by dissolution. We selected two liquid
      poly(ethylene glycols) (PEG) that dissolve CsA and create nanoparticles by
      precipitation of CsA upon water contact. Aqueous solutions of PEG and Solutol, a
      non-ionic surfactant, were well tolerated by primary human epithelial cells in
      vitro. To determine the critical water content needed for a precipitation, the
      solubility of CsA was investigated in quaternary systems of drug, solvent,
      surfactant and water. The best INS formulation showed a particle size of 505 +/-
      5 nm, a polydispersity index (PdI) of 0.23 +/- 0.03 and a neutral zeta potential
      of -0.07 +/- 0.05 mV. After single administration to porcine eyes in vitro, 3165
      +/- 597 ng(CsA)/g(cornea) were detected in corneal tissue, while the levels of
      Restasis a commercial formulation were, with 545 +/- 137 ng(CsA)/g(cornea),
      significantly lower (P<0.01). These results demonstrate that an INS is a
      promising, novel approach towards the causal treatment of inflammatory diseases
      at the anterior eye.

PMID- 23880335
TI  - Demographic, clinical, and lifestyle correlates of subjective memory complaints
      in the Australian population.
AB  - OBJECTIVES: To provide estimates of the prevalence and correlates of subjective
      memory complaints in older individuals by using population-based Australian data.
      DESIGN: 2007 National Survey of Mental Health and Well-Being. SETTING: Australia.
      PARTICIPANTS: 1,905 community-dwelling participants aged 65-85 years.
      MEASUREMENTS: Subjective memory complaints were assessed by using two questions
      reflecting: (1) poorer memory compared with others of the same age ("worse
      memory"); and (2) a decline in memory performance over the previous 5 years
      ("declining memory"). Twelve-month and lifetime diagnoses were derived from
      structured diagnostic interviews. Other correlates investigated included chronic
      physical conditions, lifestyle factors, and service use. Analyses adjusted for
      scores on the Mini-Mental State Examination. RESULTS: Subjective memory
      complaints were reported by one-third (33.5%) of respondents. Those who reported
      either complaint were more likely to report psychological distress, poor
      functioning, service use, and negative self-assessed mental and physical health.
      "Declining memory" over the past 5 years was also related to an increase in the
      rates of psychiatric disorders. After adjusting for other variables of interest,
      associations were established between subjective memory complaints and
      psychological distress, poor functioning, negative self-assessed mental health,
      and alcohol use disorders. Except for the association between "declining memory"
      and anxiety and depression, these associations remained significant after
      excluding those with scores <27 on the Mini-Mental State Examination.
      CONCLUSIONS: Subjective memory complaints were associated with several negative
      clinical characteristics that should be considered when interpreting these
      complaints. Subjective memory complaints may be valid indicators of
      psychopathology and the need for clinical assessment.

PMID- 23880336
TI  - Cortical changes associated with depression and antidepressant use in Alzheimer
      and Lewy body dementia: an MRI surface-based morphometric study.
AB  - CONTEXT: Depression is common in dementia, especially in the early stages, with
      important clinical implications, but the etiology is unknown and most likely
      heterogeneous. Antidepressant use in the elderly without dementia has previously
      been shown to be associated with high risks of adverse events and with structural
      brain alterations. OBJECTIVE: To investigate cortical changes associated with
      depression and antidepressant use in patients with mild Alzheimer's disease (AD)
      and Lewy body dementia (LBD). METHODS: 74 subjects with mild AD and LBD from
      geriatric and psychiatry outpatient clinics in Western Norway were included. The
      Montgomery-Asberg Depression Rating Scale (MADRS) was used to assess depression.
      Automatic preprocessing using Freesurfer included steps for white and grey matter
      surface reconstruction. The resulting cortical thickness was analyzed using
      linear modeling. RESULTS: Clusters of depression-associated thinning were found
      in prefrontal and temporal areas. Treatment-associated thinning was observed in
      the parahippocampal region and was significant even after correction for age,
      sex, AD/LBD diagnosis, and MADRS scores. CONCLUSION: Depression in mild AD and
      LBD is associated with cortical thinning in prefrontal and temporal areas. The
      findings suggest that depressive symptoms in mild dementia could develop due to
      neurodegeneration in the same neural circuits that are critical for depression
      across different brain disorders. Antidepressant use in patients with mild AD and
      LBD is associated with parahippocampal thinning. Taken together with low efficacy
      of antidepressants in cognitively impaired patients and high risks of adverse
      events, our results suggest a need to re-evaluate the treatment approaches for
      depression and the role of antidepressants in patients with dementia.

PMID- 23880337
TI  - Endoplasmic reticulum localization of poly(omega-aminohexyl methacrylamide)s
      conjugated with (L-)-arginines in plasmid DNA delivery.
AB  - In this work, we first synthesized a omega-amino group Boc-protected poly(omega
      aminohexyl methacrylamide) PAHMAA-Boc precursor via controlled reversible
      addition-fragmentation chain transfer (RAFT) polymerization of the Boc-AHMAA
      monomer in THF solution, and poly(omega-aminohexyl methacrylamide) (PAHMAA) was
      then prepared via Boc deprotection, and was further conjugated with (L-)
      arginines at the omega-amino group sites to give a series of new (L-)-arginine
      conjugated PAHMAA-R7, PAHMAA-R16 and PAHMAA-R22. Employing these PAHMAA and
      PAHMAA-Rs as functional gene vectors, their plasmid DNA binding affinities were
      examined by agarose gel retardant assay. By means of dynamic light scattering
      (DLS), mean particle sizes and zeta potentials of the polyplexes were analyzed.
      Moreover, cytotoxicities of the PAHMAA and PAHMAA-Rs were evaluated by MTT and
      lactate dehydrogenase (LDH) release assays with COS-7 cells, and luciferase and
      EGFP gene transfection efficacies by these vectors were assayed in COS-7 and HeLa
      cells. Furthermore, intracellular uptake of the vector/Cy3-labeled pDNA
      polyplexes was studied with a flow cytometer (FACS), and the most efficient
      PAHMAA-R16 vector was employed to investigate the endocytic gateways with various
      inhibitors. In addition, colocalization of the Cy3-labeled pDNA and Oregon Green
      labeled PAHMAA-R16 vector in the intracellular organelles of COS-7 cells was
      visualized on a fluorescence microscopy. As a result, it was revealed that the
      PAHMAA-R vectors showed lower cytotoxicities and transfection efficacies
      significantly higher than those of the PAHMAA, strongly depending on their
      percentage of arginine conjugation, and that the results of endocytic
      inhabitation and fluorescence colocalization in endoplasmic reticulum may suggest
      a caveolae-mediated efficient intracellular trafficking route for the synthesized
      PAHMAA-R vectors.

PMID- 23880338
TI  - The effect of lipid nanoparticle PEGylation on neuroinflammatory response in
      mouse brain.
AB  - Nanocarrier-based drug delivery systems have attracted wide interest for the
      treatment of brain disease. However, neurotoxicity of nanoparticle has limited
      their therapeutic application. Here we demonstrated that lipid nanoparticles
      (LNs) accumulated in the brain parenchyma within 3 h of intravenous injection to
      mice and persisted for more than 24 weeks, coinciding with a dramatic activation
      of brain microglia. Morphological characteristic of microglial activation also
      observed in LNs-treated Cx3cr1GFP/+ mice. In vivo study with two-photon confocal
      microscopy revealed abnormal Ca2+ waves in microglia following LNs injection. The
      correlated activation of caspase-1, IL-1beta and neurovascular damage following
      LNs injection was attenuated in P2X7-/- mice. PEGylation of LNs reduced
      correlated nanoparticles aggregation. Moreover, PEGylation of LNs ameliorated the
      P2X7/caspase-1/IL-1beta signalling-dependent microglia activation and
      neurovascular damage. In conclusion, PEGylation of LNs is a promising biomaterial
      for brain-targeted therapy that inhibits P2X77-dependent neuroinflammatory
      response.

PMID- 23880339
TI  - Hydrophobic modification of low molecular weight polyethylenimine for improved
      gene transfection.
AB  - Hydrophobic modification of low molecular weight (LMW) polyethylenimine (PEI) is
      known to increase gene transfection efficiency of LMW PEI. However, few studies
      have explored how the conjugated hydrophobic groups influence the properties of
      the modified LMW PEI mainly due to difficulties in obtaining well defined final
      product compositions and limitations in current chemical synthesis routes. The
      aim of this study was to modify LMW PEI (Mn 1.8 kDa, PEI-1.8) judiciously with
      different hydrophobic functional groups and to investigate how hydrophobicity,
      molecular structure and inclusion of hydrogen bonding properties in the
      conjugated side groups as well as the conjugation degree (number of primary amine
      groups of PEI-1.8 modified with hydrophobic groups) influence PEI-1.8 gene
      transfection efficiency. The modified polymers were characterized for DNA binding
      ability, particle size, zeta potential, in vitro gene transfection efficiency and
      cytotoxicity in SKOV-3 human ovarian cancer and HepG2 human liver carcinoma cell
      lines. The study shows that modified PEI-1.8 polymers are able to condense
      plasmid DNA into cationic nanoparticles, of sizes ~100 nm, whereas unmodified
      polymer/DNA complexes display larger particle sizes of 2 MUm. Hydrophobic
      modification also increases the zeta potential of polymer/DNA complexes.
      Importantly, modified PEI-1.8 shows enhanced transfection efficiency over the
      unmodified counterpart. Higher transfection efficiency is obtained when PEI-1.8
      is modified with shorter hydrophobic groups (MTC-ethyl) as opposed to longer ones
      (MTC-octyl and MTC-deodecyl). An aromatic structured functional group (MTC
      benzyl) also enhances transfection efficiency more than an alkyl functional group
      (MTC-octyl). An added hydrogen-bonding urea group in the conjugated functional
      group (MTC-urea) does not enhance transfection efficiency over one without urea
      (MTC-benzyl). The study also demonstrates that modification degree greatly
      influences gene transfection, and ~100% substitution of primary amine groups
      leads to significantly lower gene transfection efficiency. These findings provide
      insights to modification of PEI for development of effective and non-cytotoxic
      non-viral vectors.

PMID- 23880340
TI  - Effect of polydextrose and soluble maize fibre on energy metabolism, metabolic
      profile and appetite control in overweight men and women.
AB  - High-fibre diets offer several beneficial health effects. The objective of the
      present study was to investigate whether replacement of 30 % of the available
      carbohydrates with polydextrose (PDX) or soluble maize fibre (SCF) at breakfast
      and lunch would result in an increased fat oxidation rate and satiety, which may
      be of relevance for body weight control and diabetes prevention. In a single
      blind, randomised cross-over study, eighteen overweight men and women underwent
      four different dietary interventions, which consisted of a PDX diet, a SCF diet
      and two control diets (full energetic and isoenergetic, comparable with PDX with
      respect to g or energy percentage of macronutrients, respectively). Glycaemic
      profile, energy expenditure and substrate oxidation were measured for 24 h in a
      respiration chamber. Circulating insulin, NEFA and TAG concentrations were
      determined over a 14 h period during daytime. Appetite ratings were assessed
      using visual analogue scales. The replacement of available carbohydrates with PDX
      or SCF reduced the peak glucose response, which was accompanied by reduced
      postprandial insulin responses. Moreover, higher concentrations of circulating
      NEFA were observed after consumption of both fibre diets, which were accompanied
      by an increased fat oxidation over 24 h. This effect was mainly attributed to the
      lower energetic value of the fibre diets and not to the fibres per se. Besides
      increasing fat oxidation, PDX exerted a pronounced suppressive effect on appetite
      ratings. The replacement of available carbohydrates with PDX may be of special
      interest because of its beneficial effects on metabolic profile and it may affect
      body weight control in the long term.

PMID- 23880341
TI  - Melatonin elevates apoptosis in human platelets via ROS mediated mitochondrial
      damage.
AB  - Melatonin is a pineal hormone that regulates circadian and seasonal rhythms. The
      chronobiotic role of melatonin corresponds with a repertoire of pharmacological
      properties. Besides, it has a wide range of therapeutic applications. However,
      recent studies have demonstrated its direct interaction with platelets: at
      physiological concentration it promotes platelet aggregation; on the other hand,
      at pharmacological doses it raises intracellular Ca(2+) leading to platelet
      activation, thrombus formation and cardiovascular disorders. In order to further
      probe its effects on platelets, the current study targeted platelet apoptosis and
      melatonin was found to stimulate apoptosis. The mitochondrial pathway of
      apoptosis was mainly investigated because of its susceptibility to oxidative
      stress-inducing factors including therapeutic and dietary elements. Melatonin
      significantly increased the generation of intracellular ROS and Ca(2+),
      facilitating mitochondrial membrane depolarization, cytochrome c release, caspase
      activation, protein phosphorylation and phosphatidylserine externalization.
      Further, the overall toxicity of melatonin on platelets was confirmed by MTT and
      lactate dehydrogenase assays. The elevated rate of platelet apoptosis has far
      reaching consequences including thrombocytopenia. Besides, platelets undergoing
      apoptosis release microparticles, which fuel thrombus formation and play a
      significant role in the pathophysiology of a number of diseases. In many parts of
      the world melatonin is an over-the-counter dietary supplement and alternative
      medicine. Since, melatonin displays platelet proapoptotic effect at a
      concentration attainable through therapeutic dosage, the present study sends a
      warning signal to the chronic use of melatonin as a therapeutic drug and
      questions its availability without a medical prescription. 

PMID- 23880342
TI  - Induction of cytoprotective autophagy in PC-12 cells by cadmium.
AB  - Laboratory data have demonstrated that cadmium (Cd) may induce neuronal
      apoptosis. However, little is known about the role of autophagy in neurons. In
      this study, cell viability decreased in a dose- and time-dependent manner after
      treatment with Cd in PC-12 cells. As cells were exposed to Cd, the levels of LC3
      II proteins became elevated, specific punctate distribution of endogenous LC3-II
      increased, and numerous autophagosomes appeared, which suggest that Cd induced a
      high level of autophagy. In the late stages of autophagy, an increase in the
      apoptosis ratio was observed. Likewise, pre-treatment with chloroquine (an
      autophagic inhibitor) and rapamycin (an autophagic inducer) resulted in an
      increased and decreased percentage of apoptosis in contrast to other Cd-treated
      groups, respectively. The results indicate that autophagy delayed apoptosis in Cd
      treated PC-12 cells. Furthermore, co-treatment of cells with chloroquine reduced
      autophagy and cell activity. However, rapamycin had an opposite effect on
      autophagy and cell activity. Moreover, class III PI3 K/beclin-1/Bcl-2 signaling
      pathways served a function in Cd-induced autophagy. The findings suggest that Cd
      can induce cytoprotective autophagy by activating class III PI3 K/beclin-1/Bcl-2
      signaling pathways. In sum, this study strongly suggests that autophagy may serve
      a positive function in the reduction of Cd-induced cytotoxicity. 

PMID- 23880343
TI  - Substrate binding to a GH131 beta-glucanase catalytic domain from Podospora
      anserina.
AB  - beta-Glucanases have been utilized widely in industry to treat various
      carbohydrate-containing materials. Recently, the Podospora anserina beta
      glucanase 131A (PaGluc131A) was identified and classified to a new glycoside
      hydrolases GH131 family. It shows exo-beta-1,3/exo-beta-1,6 and endo-beta-1,4
      glucanase activities with a broad substrate specificity for laminarin, curdlan,
      pachyman, lichenan, pustulan, and cellulosic derivatives. Here we report the
      crystal structures of the PaGluc131A catalytic domain with or without ligand
      (cellotriose) at 1.8A resolution. The cellotriose was clearly observed to occupy
      the +1 to +3 subsites in substrate binding cleft. The broadened substrate binding
      groove may explain the diverse substrate specificity. Based on our crystal
      structures, the GH131 family enzyme is likely to carry out the hydrolysis through
      an inverting catalytic mechanism, in which E99 and E139 are supposed to serve as
      the general base and general acid. 

PMID- 23880344
TI  - Senescent endothelial cells are prone to TNF-alpha-induced cell death due to
      expression of FAS receptor.
AB  - The senescent endothelial cells show various phenotypes which can increase the
      incidence of inflammatory cardiovascular diseases, but the fundamental basis for
      such phenotypic changes of senescing cells remains to be elucidated. This study
      was undertaken to find transmembrane receptors that might be highly expressed in
      senescent endothelial cells and play a key role in cell death signal
      transduction. Comparison of mRNA expression in young and senescent human
      umbilical vein endothelial cells, using a cDNA microarray method, provided a list
      of transmembrane receptors including the FAS receptor (tumor necrosis factor
      receptor superfamily member 6) whose expression levels were significantly
      increased by cellular senescence. Additional studies focused on FAS demonstrated
      that a high expression of FAS receptor in senescent endothelial cells is
      responsible for the susceptibility to apoptotic cell death, as the siRNA-mediated
      suppression of FAS expression in senescent cells prevented the cell death, and
      overexpression of exogenous FAS in young cells increased cell death. We also
      verified that FAS expression level was closely associated with the activation of
      caspase-3 and caspase-9 involved in apoptosis. The senescence-induced
      transmembrane receptors including the FAS receptor may provide novel therapeutic
      targets to prevent cardiovascular diseases. 

PMID- 23880345
TI  - TXNIP interacts with hEcd to increase p53 stability and activity.
AB  - The p53 protein plays a central role in cell cycle arrest and apoptosis in
      response to diverse stress stimuli. Human ecdysoneless (hEcd) is known for its
      role in stabilizing the p53 protein level and increasing p53-mediated
      transcription. Here, we report that thioredoxin interacting protein (TXNIP), a
      member of the tumor suppressor family, interacts with hEcd and decreases MDM2
      mediated p53 ubiquitination, leading to p53 stabilization and an increase in p53
      activity. The ectopic overexpression of both TXNIP and Ecd increased actinomycin
      D-mediated cell death in MCF-7 cells, whereas knockdown of TXNIP and Ecd
      decreased cell death. These results show that TXNIP is a new regulator of the Ecd
      MDM2-p53 loop. 

PMID- 23880346
TI  - TLE3, transducing-like enhancer of split 3, suppresses osteoblast differentiation
      of bone marrow stromal cells.
AB  - In senile osteoporosis the balance of adipogenesis and osteoblastogenesis in bone
      marrow stromal cells (BMSCs) is disrupted so that adipogenesis is increased with
      respect to osteoblastogenesis, and as a result, bone mass is decreased. While the
      molecular mechanisms controlling the balance between osteoblastogenesis and
      adipogenesis are of great interest, the exact nature of the signals regulating
      this process remains to be determined. In general, adipogenesis is a reciprocal
      relationship with osteoblastogenesis in BMSCs. Recently transducin-like enhancer
      of split 3 (TLE3), was reported to enhance adipogenesis in pre adipocytes.
      However, the effect of TLE3 on osteoblast differentiation of BMSCs is completely
      unknown. Here we report that TLE3 not only enhances adipocyte differentiation in
      BMSCs but also suppresses osteoblast differentiation. Firstly we examined the
      expression and localization of TLE3. We found that TLE3 is expressed in the
      nucleus of bone marrow stromal cells and that over-expression of TLE3 induced
      adipocyte differentiation and suppressed ALP activity induced by treatment with
      BMP2 in these cells. In contrast, adipocyte differentiation was decreased and ALP
      activity increased when endogenous TLE3 was knocked down by shRNA in BMSCs. To
      examine the mechanism by which TLE3 is able to suppress osteoblast
      differentiation, we focused on Runx2, a transcription factor essential for
      osteoblast differentiation. We found that TLE3 strongly suppressed ALP activity
      and OSE2-luciferase activity induced by Runx2 and this repression of Runx2 by
      TLE3 occurs via HDACs because treatment with TSA, a class I and II HDAC
      inhibitor, rescued this repression. In conclusion, we identify TLE3 as a
      suppressor of BMSC differentiation in osteoblast lineage cells in vitro. Our data
      suggest that TLE3 activity may be a key in balancing adipocyte and osteoblast
      differentiation in the adult bone marrow microenvironment. 

PMID- 23880348
TI  - An increased replication fidelity mutant of foot-and-mouth disease virus retains
      fitness in vitro and virulence in vivo.
AB  - In a screen for RNA mutagen-resistant foot-and-mouth disease virus (FMDV)
      strains, we isolated an FMDV mutant with RNA-dependent RNA polymerase (RdRp) R84H
      substitution. This mutant, selected under the mutagenic pressure of 5
      fluorouracil (5-FU), is resistant not only to 5-FU but also to other two RNA
      mutagens, 5-azacytidine and ribavirin, suggesting that the RdRp R84H mutant is a
      high fidelity variant. Subsequently, the increased fidelity of this mutant was
      verified through analysis of mutation frequency, which revealed a 1.4-fold
      enhancement in RdRp fidelity compared with the wild-type virus. Further studies
      indicated that the R84H mutant exhibited slightly increased fitness in vitro, and
      its virulence was not reduced in suckling mice. These results indicated that an
      increase in RdRp fidelity does not always correlate with reduced virus fitness
      and virus attenuation. Thus, this isolated R84H mutant provides a new platform to
      examine the evolutionary dynamics of fidelity-changing RNA viruses, such as
      mutagen resistance, fitness and virulence. 

PMID- 23880349
TI  - Uterus transplantation from a deceased donor.
AB  - OBJECTIVE: To demonstrate the technique for uterus retrieval and transplantation
      from a multiorgan donor. DESIGN: Video presentation of our case report. The video
      uses animation to demonstrate the technique. Institutional Review Board (IRB)
      approval was obtained. SETTING: University hospital. PATIENT(S): A 21-year-old
      woman with complete mullerian agenesis. INTERVENTION(S): Uterus
      allotransplantation has been performed from a deceased donor. MAIN OUTCOME
      MEASURE(S): Acquirement of cyclic menstrual function. RESULT(S): This video
      demonstrates the technique for uterus retrieval, perfusion, and transplantation.
      The recipient patient has been monitored regularly for vascular flow,
      immunosuppression, and infection control since the operation. CONCLUSION(S):
      Uterus transplantation requires extensive evaluation of the recipient and donor
      by an experienced multidisciplinary transplantation team both pre- and
      postoperatively. It has major risks related to surgery, immunosuppression, and
      pregnancy. Uterus transplantation might be considered promising only after the
      birth of a near-term healthy baby.

PMID- 23880347
TI  - Plasma cis-vaccenic acid and risk of heart failure with antecedent coronary heart
      disease in male physicians.
AB  - BACKGROUND & AIMS: Although an inverse association of red blood cell cis-vaccenic
      acid and risk of myocardial infarction has been reported, it is unclear whether
      cis-vaccenic acid might lower the risk of heart failure (HF) with antecedent
      coronary heart disease (CHD). We sought to examine the relation of plasma cis
      vaccenic acid with HF with antecedent CHD. METHODS: This nested case-control
      study was based on 788 incident HF cases (of whom 258 cases had antecedent CHD)
      and 788 controls. Each control was selected using a risk set sampling technique
      at the time of the occurrence of the index case and matched on year of birth, age
      at blood collection, and race. Fatty acids were measured using gas chromatography
      and incident HF was self-reported on annual questionnaires and validation in a
      subsample using medical records. RESULTS: In a multivariable conditional logistic
      regression, the odds ratio (95% confidence interval) for HF with prior CHD were
      1.0 (ref), 0.72 (0.33-1.57), 0.28 (0.12-0.67), and 0.23 (0.09-0.58) across
      consecutive quartiles of cis-vaccenic acid (p_trend 0.0004). Each standard
      deviation of cis-vaccenic acid was associated with a 41% lower risk of HF with
      antecedent CHD (95% CI: 17%-59%) in a multivariable adjusted model. CONCLUSIONS:
      Our data suggest that higher plasma levels of plasma cis-vaccenic acid may be
      associated with a lower risk of HF with antecedent CHD. Confirmation of these
      results in the general population including women and other ethnic groups is
      warranted.

PMID- 23880350
TI  - Correlation between platelet and brain PLA(2) activity.
AB  - The phospholipase A2 (PLA2) enzymes have been implicated in several
      neuropsychiatry disorders and activity alterations have been described in brain
      and platelet. Since brain tissue is not readily available for the measurement of
      PLA2 activity, it would be of interest to test directly whether PLA2 activities
      in both tissues are correlated. We performed this task assessing PLA2 activity in
      platelets and hippocampus collected simultaneously from 19 patients undergoing
      temporal lobectomy for treatment of refractory epilepsy. Our findings suggest
      that total PLA2 activity in platelets may reflect the total activity of the
      enzyme in the brain (rs=0.59, p=0.008). However in our sample no correlations
      were found between the subgroups of the enzyme in brain and in platelets. This
      lack of correlations may be due to different effects of drug treatment on the
      PLA2 subtypes. In face of the difficulty to obtain brain tissues from living
      patients, further studies with larger drug-free samples are warranted to clarify
      whether the use of platelets is a reliable strategy to reflect the subtypes of
      PLA2 activity in the brain. 

PMID- 23880351
TI  - Long-term coffee consumption in relation to fracture risk and bone mineral
      density in women.
AB  - High consumption of coffee has been suggested to reduce the risk of some late
      onset diseases and death but also to contribute to the development of
      osteoporotic fractures. Results of previous fracture studies have been
      inconsistent, and a comprehensive study is needed. The longitudinal population
      based Swedish Mammography Cohort, including 61,433 women born in 1914-1948, was
      followed up from 1987 through 2008. Coffee consumption was assessed with repeated
      food frequency questionnaires. During follow-up, 14,738 women experienced
      fracture of any type, and 3,871 had a hip fracture. In a subcohort (n = 5,022),
      bone density was measured and osteoporosis determined (n = 1,012). After
      multivariable adjustment, there was no evidence of a higher rate of any fracture
      (hazard ratio per 200 mL coffee = 0.99; 95% confidence interval: 0.98, 1.00) or
      hip fracture (hazard ratio per 200 mL coffee = 0.97, 95% confidence interval:
      0.95, 1.00) with increasing coffee consumption. A high coffee intake (>=4 cups
      daily) versus a low intake (<1 cup daily) was associated with a 2%-4% lower bone
      density, depending on site (P < 0.001), but the odds ratio for osteoporosis was
      only 1.28 (95% confidence interval: 0.88, 1.87). Thus, high coffee consumption
      was associated with a small reduction in bone density that did not translate into
      an increased risk of fracture. 

PMID- 23880352
TI  - Re: "Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a
      prospective cohort study".

PMID- 23880353
TI  - Contribution of seasonality in transmission of Mycobacterium tuberculosis to
      seasonality in tuberculosis disease: a simulation study.
AB  - A seasonal rise in tuberculosis (TB) notifications has been confirmed in several
      studies. Here, we examined one hypothesis for its cause: increased transmission
      of TB during wintertime due to crowding. Seasonality analysis was performed on
      actual and simulated notifications of clustered TB cases, which are considered to
      be representative of recent transmission, diagnosed from 1993 to 2004 in the
      Netherlands (n = 4,746). To test the hypothesis of winter crowding, notifications
      were simulated by adding patient delay and incubation period to an infection date
      randomly taken to be in winter in 80% of cases. The incubation periods were
      derived from frequency distributions for different TB disease localizations drawn
      from the literature. Seasonality analysis was performed using autocorrelation
      function plots and spectral analysis. Actual notifications showed strong
      seasonality in clustered TB and clustered extrapulmonary TB cases but not in
      clustered pulmonary TB cases. Analysis of simulated notifications revealed barely
      significant seasonality only in extrapulmonary TB cases. Our results suggest that
      increased transmission of TB during wintertime is unlikely to be the only cause
      of the seasonal peak in TB notifications. A factor closer to the notification
      date probably contributes to the seasonality observed in TB notifications. 

PMID- 23880354
TI  - Infection after vertebroplasty or kyphoplasty. A series of nine cases and review
      of literature.
AB  - BACKGROUND CONTEXT: Percutaneous augmentation with bone cement is a widely
      accepted modality of treatment for thoracic and lumbar vertebral osteoporotic
      fractures. Infection after vertebroplasty or kyphoplasty is a serious, yet,
      rarely reported complication. PURPOSE: To present a case series with a long-term
      follow-up of spinal infection after vertebroplasty/kyphoplasty with analysis of
      preoperative condition, risk factors, diagnostic findings, time before
      reoperation, causative organism, treatment, and outcome. STUDY DESIGN: A
      retrospective, uncontrolled clinical case series in a single institution. PATIENT
      SAMPLE: Between January 1997 and June 2012, 1,307 patients underwent percutaneous
      vertebroplasty or kyphoplasty. Six cases had postoperative infection (0.46%) and
      three additional cases were referred from other institutions for salvage
      treatment. OUTCOME MEASURES: Perioperative assessment included visual analog
      scale, clinical, laboratory, and imaging findings, and activities of daily living
      at the end of the follow-up. METHODS: Nine patients were included: six females
      and three males (mean age 73.8 years). Comorbidities were found in all patients.
      Kyphoplasty had been done in five patients and vertebroplasty in four. RESULTS:
      The interval between augmentation and revision surgery ranged from 10 to 395 days
      with a mean of 118.4 days. Three cases with early infection presented within 1
      month. Infection parameters were high in all patients at readmission. All
      patients were treated surgically except one case who died before the planned
      revision surgery. In all cases, debridement and corpectomy were done through
      anterior approaches combined with posterior instrumentation. The most common
      causative organism was Staphylococcus aureus in three cases. Mean follow-up
      period after the revision surgery was 26.68 months, excluding two patients who
      died early in the follow-up (within 4 months). This amounts to a mortality rate
      of 33.3% perioperatively. At the end of follow-up, two patients had unrestricted
      activities and one patient required a walker. Of three paraparetic patients, two
      improved functionally and could walk unassisted and one improved but still used a
      wheelchair. CONCLUSIONS: Although vertebroplasty and kyphoplasty are minimally
      invasive interventions, postoperative infection can develop into life-threatening
      complications. This should be accounted for, in decision making in the elderly
      age group most commonly affected by osteoporotic fractures and especially in
      suspicious and high-risk immune-compromised patients.

PMID- 23880355
TI  - Dietary intake of carbohydrates and risk of type 2 diabetes: the European
      Prospective Investigation into Cancer-Norfolk study.
AB  - In the present study, we investigated the association between dietary intake of
      carbohydrates and the risk of type 2 diabetes. Incident cases of diabetes (n 749)
      were identified and compared with a randomly selected subcohort of 3496
      participants aged 40-79 years. For dietary assessment, we used 7 d food diaries
      administered at baseline. We carried out modified Cox proportional hazards
      regression analyses and compared results obtained from the different methods of
      adjustment for total energy intake. Dietary intakes of total carbohydrates,
      starch, sucrose, lactose or maltose were not significantly related to diabetes
      risk after adjustment for confounders. However, in the residual method for energy
      adjustment, intakes of fructose and glucose were inversely related to diabetes
      risk. The multivariable-adjusted hazard ratios (HR) of diabetes comparing the
      extreme quintiles of intake were 0.79 (95 % CI 0.59, 1.07; P for trend = 0.03)
      for glucose and 0.62 (95 % CI 0.46, 0.83; P for trend = 0.01) for fructose. In
      the nutrient density method, only fructose was inversely related to diabetes risk
      (HR 0.65, 95 % CI 0.48, 0.88). The replacement of 5 % energy intake from SFA with
      an isoenergetic amount of fructose was associated with a 30 % lower diabetes risk
      (HR 0.69, 95 % CI 0.50, 0.96). Results of the standard and energy partition
      methods were similar to those of the residual method. These prospective findings
      suggest that the intakes of starch and sucrose are not associated, but that those
      of fructose and glucose are inversely associated with diabetes risk. Whether the
      inverse associations with fructose and glucose reflect the effect of substitution
      of these carbohydrate subtypes with other nutrients (i.e. SFA), their net higher
      intake or other nutrients associated with their intake remains to be established
      through further investigation. 

PMID- 23880356
TI  - Placental ABCA1 and ABCG1 expression in gestational disease: Pre-eclampsia
      affects ABCA1 levels in syncytiotrophoblasts.
AB  - INTRODUCTION: Transplacental feto-maternal lipid exchange through the ATP-binding
      cassette transporters ABCA1 and ABCG1 is important for normal fetal development.
      However, only scarce and conflicting data exist on the involvement of these
      transporters in gestational disease. METHODS: Placenta samples (n = 72) derived
      from common gestational diseases, including pre-eclampsia (PE), HELLP,
      intrauterine growth restriction (IUGR), intrahepatic cholestasis of pregnancy and
      gestational diabetes, were assessed for their ABCA1 and ABCG1 expression levels
      and compared to age-matched control placentas with qRT-PCR and
      immunohistochemistry. ABCA1 expression was additionally investigated with
      immunoblot in placental membrane vesicles. Furthermore, placental cholesterol and
      phospholipid contents were assessed. RESULTS: ABCA1 mRNA levels differed
      significantly between preterm and term control placentas (p = 0.0013). They were
      down-regulated in isolated PE and PE with IUGR (p = 0.0006 and p = 0.0012,
      respectively), but unchanged in isolated IUGR, isolated HELLP and other
      gestational diseases compared to gestational age-matched controls.
      Correspondingly, in PE, ABCA1 protein expression was significantly reduced in the
      apical membrane of the villous syncytiotrophoblast (p = 0.011) and in villous
      fetal endothelial cells (p = 0.036). Furthermore, in PE there was a significant
      increase in the placental content of total and individual classes of
      phospholipids which were partially correlated with diminished ABCA1 expression.
      Conversely, ABCG1 mRNA and protein levels were stable in the investigated
      conditions. CONCLUSIONS: In gestational disease, there is a specific down
      regulation of placental ABCA1 expression at sites of feto-maternal lipid exchange
      in PE. At a functional level, the increase in placental lipid concentrations
      provides indirect evidence of an impaired transport capacity of ABCA1 in this
      disease.

PMID- 23880357
TI  - Detection and assessment of electrocution in endangered raptors by infrared
      thermography.
AB  - BACKGROUND: Most European birds of prey find themselves in a poor state of
      conservation, with electrocution as one of the most frequent causes of unnatural
      death. Since early detection of electrocution is difficult, treatment is usually
      implemented late, which reduces its effectiveness. By considering that
      electrocution reduces tissue temperature, it may be detectable by thermography,
      which would allow a more rapid identification. Three individuals from three
      endangered raptor species [Spanish imperial eagle (Aquila adalberti), Lammergeier
      (Gypaetus barbatus) and Osprey (Pandion haliaetus)] were studied
      thermographically from the time they were admitted to a rehabilitation centre to
      the time their clinical cases were resolved. CASES PRESENTATION: The three
      raptors presented lesions lacking thermal bilateral symmetry and were consistent
      with electrocution of feet, wings and eyes, visible by thermography before than
      clinically; lesions were well-defined and showed a lower temperature than the
      surrounding tissue. Some lesions evolved thermally and clinically until the
      appearance of normal tissue recovered, while others evolved and became necrotic.
      A histopathological analysis of a damaged finger amputated off a Lammergeier, and
      the necropsy and histopathology examination of an osprey, confirmed the
      electrocution diagnosis. CONCLUSIONS: These results suggest that thermography is
      effective and useful for the objective and early detection and monitoring of
      electrocuted birds, and that it may prove especially useful for examining live
      animals that require no amputation or cannot be subjected to invasive
      histopathology.

PMID- 23880358
TI  - Probes for narcotic receptor mediated phenomena. 48. C7- and C8-substituted 5
      phenylmorphan opioids from diastereoselective alkylation.
AB  - The exploration of the effect of substituents at C7 and C8 of the 5
      phenylmorphans on their affinity for opioid receptors was enabled by our recently
      introduced "one pot" diastereoselective synthesis that provided C7-oxo, hydroxy
      and alkyl substituents, C8-alkyl substituted 5-phenylmorphans, and compounds that
      had a new cyclohexane ring that includes the C7 and C8 carbon atoms of the 5
      phenylmorphan. The affinity of the 5-phenylmorphans for opioid receptors is
      increased by a C8-methyl substituent, compared with its C7 analog. The affinity
      of the newly synthesized compounds is generally for the MU-opioid receptor,
      rather than the delta- or kappa-receptors. Addition of a new cyclohexane ring to
      the C7 and C8 positions on the cyclohexane ring of the 5-phenylmorphans enhances
      MU-receptor affinity, bringing the Ki to the subnanomolar level. Unexpectedly,
      the N-methyl substituted compounds generally had higher affinity than comparable
      N-phenethyl-substituted relatives. The configurations of two compounds were
      determined by single-crystal X-ray crystallographic analyses. 

PMID- 23880359
TI  - 3D-QSAR using pharmacophore-based alignment and virtual screening for discovery
      of novel MCF-7 cell line inhibitors.
AB  - The development of a novel approach for the prediction of antiestrogenic activity
      is described, bringing up to date a previous pharmacophore study. Software Phase
      has been used to derive a 3D-QSAR model based, as alignment rule, on a
      pharmacophore built on three compounds highly active against MCF-7 cell line.
      Five features comprised the pharmacophore: two hydrogen-bond acceptors, one
      hydrogen-bond donor, and two aromatic rings. The sequential 3D-QSAR yielded a
      test set q(2) equal to 0.73 and proved to be predictive with respect to an
      external test set of 21 compounds (r(2) = 0.69). The model was used to detect new
      MCF-7 inhibitors through 3D-database searching and identified fourteen compounds
      that were subsequently tested in vitro against the MCF-7 human breast
      adenocarcinoma cell line. Eleven out of the fourteen compounds exhibited
      inhibitory activity with IC50 values ranging between 30 and 186 MUM. The results
      of the study confirmed the fundamental validity of the chosen approach as a hit
      discovery tool. 

PMID- 23880360
TI  - A TRiP to heart failure.

PMID- 23880361
TI  - Pancreas and liver resection in Jehovah's Witness patients: feasible and safe.
AB  - BACKGROUND: Jehovah's Witness (JW) patients undergoing liver or pancreas surgery
      represent a challenging ethical and medical problem, with few reports about their
      optimal management. STUDY DESIGN: To analyze the perioperative outcomes of JW
      patients submitted to hepatic or pancreatic resection, clinicopathologic data of
      JW patients who underwent surgical exploration for a hepatic or pancreatic tumor
      between March 1996 and July 2011 were reviewed retrospectively. RESULTS:
      Clinicopathologic data of 27 patients, 28 explorations, and 25 resections were
      included. Median age was 58 years (range 28 to 75 years) and 20 patients were
      female. Three patients were explored and deemed unresectable. Fifteen hepatic
      resections (9 segmentectomy or bi/trisegmentectomy, 6 hemi-hepatectomy or
      extended hepatectomy) and 10 pancreatic resections (6 pancreaticoduodenectomy, 4
      distal pancreatectomy/splenectomy) were reviewed; additional organs were resected
      in 5 patients (2 gastrectomy, 1 colectomy, 1 nephrectomy, 1 adrenalectomy, 1
      salpingoophorectomy). Median estimated blood loss for the hepatectomies was 400
      mL (range 100 to 1,500 mL) and for the pancreatectomies was 400 mL (range 250 to
      1,800 mL). Six patients received preoperative erythropoietin; hemodilution was
      used in 9 patients and 3 had Cell Saver-generated autotransfusions. Median
      preoperative hemoglobin was 12.5 g/dL (range 9.5 to 14.4 g/dL) and median
      postoperative hemoglobin was 10.4 g/dL (range 9 to 12.4 g/dL). In-hospital
      mortality was 0%. One patient required re-exploration for decreasing hemoglobin
      and refusal of transfusion; a total of 11 complications developed in 7 other
      patients (5 wound infection/breakdown, 1 urinary tract infection, 1 ileus, 1
      nausea/vomiting, 1 lymphedema, 1 ascites, and 1 ARDS). Median hospital stay was 7
      days (range 4 to 23 days). CONCLUSIONS: Pancreatic and liver resection can be
      done safely in selected JW patients who refuse blood products by using a variety
      of blood-conservation techniques to help spare red cell mass.

PMID- 23880362
TI  - Mesenchymal stem cell transformation and sarcoma genesis.
AB  - MSCs are hypothesized to potentially give rise to sarcomas after transformation
      and therefore serve as a good model to study sarcomagenesis. Both spontaneous and
      induced transformation of MSCs have been reported, however, spontaneous
      transformation has only been convincingly shown in mouse MSCs while induced
      transformation has been demonstrated in both mouse and human MSCs. Transformed
      MSCs of both species can give rise to pleomorphic sarcomas after transplantation
      into mice, indicating the potential MSC origin of so-called non-translocation
      induced sarcomas. Comparison of expression profiles and differentiation
      capacities between MSCs and sarcoma cells further supports this. Deregulation of
      P53- Retinoblastoma-, PI3K-AKT-and MAPK pathways has been implicated in
      transformation of MSCs. MSCs have also been indicated as cell of origin in
      several types of chromosomal translocation associated sarcomas. In mouse models
      the generated sarcoma type depends on amongst others the tissue origin of the
      MSCs, the targeted pathways and genes and the differentiation commitment status
      of MSCs. While some insights are glowing, it is clear that more studies are
      needed to thoroughly understand the molecular mechanism of sarcomagenesis from
      MSCs and mechanisms determining the sarcoma type, which will potentially give
      directions for targeted therapies. 

PMID- 23880363
TI  - Self-adjuvanting influenza candidate vaccine presenting epitopes for cell
      mediated immunity on a proteinaceous multivalent nanoplatform.
AB  - We exploit the features of a virus-like particle, adenoviral dodecahedron (Ad
      Dd), for engineering a multivalent vaccination platform carrying influenza
      epitopes for cell-mediated immunity. The delivery platform, Ad Dd, is a
      proteinaceous, polyvalent, and biodegradable nanoparticle endowed with remarkable
      endocytosis activity that can be engineered to carry 60 copies of a peptide.
      Influenza M1 is the most abundant influenza internal protein with the conserved
      primary structure. Two different M1 immunodominant epitopes were separately
      inserted in Dd external positions without destroying the particles' dodecahedric
      structure. Both kinds of DdFluM1 obtained through expression in baculovirus
      system were properly presented by human dendritic cells triggering efficient
      activation of antigen-specific T cells responses. Importantly, the candidate
      vaccine was able to induce cellular immunity in vivo in chickens. These results
      warrant further investigation of Dd as a platform for candidate vaccine, able to
      stimulate cellular immune responses. 

PMID- 23880364
TI  - Evaluation of a new vaccination program for infants born to HBsAg-positive
      mothers in Stockholm County.
AB  - To overcome previous shortcomings in the routines for prophylaxis to newborns of
      hepatitis B infected pregnant women, we established a new program in 2005. This
      program combined monovalent hepatitis B vaccine at birth and at one month with
      three doses of hexavalent vaccine, including a hepatitis B vaccine component, at
      3, 5 and 12 months, respectively. The hexavalent vaccine and follow-up serologies
      were administered at the well baby clinics. Three hundred and eighty babies born
      to 356 HBsAg positive mothers (9% HBeAg positive), were evaluated. Twenty-two
      children were lost to follow-up, 329 of the remaining 358 children (92%)
      completed follow-up serology at ages 13-18 months, with protective anti-HBs
      levels in 99%. For comparison, in a previous cohort from 2000 to 2001, only 63%
      completed follow-up serology. We conclude that the adherence to the new program
      was good and that it resulted in a very high rate of protective antibody levels. 

PMID- 23880365
TI  - Tetraspanin-3 regulates protective immunity against Eimeria tenella infection
      following immunization with dendritic cell-derived exosomes.
AB  - The effects of immunization with dendritic cell (DC) exosomes, which had been
      incubated with a tetraspanin-3 (Tspan-3) blocking antibody (Ab) or with an
      isotype-matched non-immune IgG, were studied using an experimental model of
      Eimeria tenella avian coccidiosis. Purified exosomes from cecal tonsil and
      splenic DCs expressed Tspan-3 protein. Chickens injected with exosomes incubated
      with the control IgG and derived from cecal tonsil DCs preloaded in vitro with E.
      tenella Ag had Ag-immunostaining cells in the ceca, but not the spleen.
      Conversely, Ag-containing cells were found only in the spleen, but not the ceca,
      of chickens given IgG treated splenic DC exosomes. Interestingly, chickens that
      received exosomes incubated with Tspan-3 Ab had Ag-containing cells observed in
      both lymphoid organs following administration of exosomes from either DC
      population. After injection of exosomes non-incubated with Tspan-3 Ab, greater
      numbers of cells secreting interleukin-2 (IL-2), IL-16, interferon-gamma, and E.
      tenella-reactive Abs were observed in the cecal tonsils of chickens immunized
      with cecal DC exosomes compared with the spleen. By contrast, more cytokine-and
      Ab-producing cells were present in the spleen of chickens given splenic DC
      exosomes compared with the ceca. Incubation with Tspan-3 Ab gave similar numbers
      of cytokine- and Ab-producing cells in the cecal tonsils and spleen regardless of
      the source of exosomes. Immunization with E. tenella Ag-loaded cecal tonsil DC
      exosomes increased in vivo resistance against subsequent E. tenella infection.
      Increased protection against infection following cecal DC exosome immunization
      was partially blocked by incubation of exosomes with Tspan-3 Ab. These results
      suggest that Tspan-3 is involved in the tissue distribution, as well as cytokine
      and Ab production, following DC exosome administration, and that Tspan-3
      contributes to in vivo protection against experimental E. tenella challenge
      infection following exosomal immunization. 

PMID- 23880366
TI  - TLR2-targeted secreted proteins from Mycobacterium tuberculosis are protective as
      powdered pulmonary vaccines.
AB  - Despite considerable research efforts towards effective treatments, tuberculosis
      (TB) remains a staggering burden on global health. Suitably formulated sub-unit
      vaccines offer potential as safe and effective generators of protective immunity.
      The Mycobacterium tuberculosis antigens, cutinase-like proteins (Culp) 1 and 6
      and MPT83, were conjugated directly to the novel adjuvant Lipokel (Lipotek Pty
      Ltd), a TLR2 ligand that delivers antigen to immune cells in a self-adjuvanting
      context. Protein-Lipokel complexes were formulated as dry powders for pulmonary
      delivery directly to the lungs of mice by intra-tracheal insufflation, leading to
      recruitment of neutrophils and antigen presenting cell populations to the lungs
      at 72 h, that persisted at 7 days post immunisation. Significant increases in the
      frequency of activated dendritic cells were observed in the mediastinal lymph
      node (MLN) at 1 and 4 weeks after homologous boosting with protein-Lipokel
      vaccine. This was associated with the increased recruitment of effector CD4(+)
      and CD8(+) T-lymphocytes to the MLN and systemic antigen-specific, IFN-gamma
      producing T-lymphocyte and IgG responses. Notably, pulmonary immunisation with
      either Culp1-6-Lipokel or MPT83-Lipokel powder vaccines generated protective
      responses in the lungs against aerosol M. tuberculosis challenge. The successful
      combination of TLR2-targeting and dry powder vaccine formulation, together with
      important practical benefits, offers potential for pulmonary vaccination against
      M. tuberculosis.

PMID- 23880367
TI  - Arsenic trioxide induced endoplasmic reticulum stress in laryngeal squamous cell
      line Hep-2 cells.
AB  - Arsenic trioxide (As2O3) has been used in the treatment of acute promyelocytic
      leukemia (APL) and many malignant solid tumors. Recently, endoplasmic reticulum
      (ER) stress plays an important role in As2O3-treated laryngeal squamous cell line
      Hep-2 cells. In the present work, the expression of ER stress-related proteins
      was investigated in As2O3-treated Hep-2 cells. The results showed that As2O3
      increased the expression of GRP78, CHOP, phosphorylated eIF2alpha and ATF4, all
      of which are the molecule of ER stress. Therefore, As2O3 induced ER stress in Hep
      2 cells. 

PMID- 23880368
TI  - Evaluation of the vestibulo-ocular reflex using sinusoidal off-vertical axis
      rotation in patients with canal paresis.
AB  - OBJECTIVE: The vestibulo-ocular reflex (VOR) was studied to determine the utility
      of off-vertical axis rotation (OVAR) in evaluating vestibular function in
      patients with canal paresis (CP). Our goal was to determine whether there is any
      correlation between caloric responses and sinusoidal rotatory responses. METHODS:
      Subjects were rotated in a sinusoidal pattern with eyes open in complete
      darkness. Frequencies of 0.4 and 0.8Hz with a maximum angular velocity of 60
      degrees /s at either earth-vertical axis rotation (EVAR) or OVAR were used.
      RESULTS: Twenty-three control subjects and 21 patients with CP were investigated.
      Results showed that (1) the VOR gain difference between EVAR and OVAR in the CP
      patients was not significant at 0.4Hz and at 0.8Hz; (2) the gain during 0.4Hz
      EVAR was less in the bilateral CP patients compared to controls; and (3) the VOR
      gain of the affected side at 0.8Hz was significantly less during OVAR than during
      EVAR. CONCLUSION: We concluded that the absence or reduction of caloric responses
      does not indicate the absence of vestibular function. In addition, separation
      analysis of the VOR gain of affected and intact sides is useful for evaluating
      laterality of otolith function in patients with CP.

PMID- 23880369
TI  - Mechanically overloading collagen fibrils uncoils collagen molecules, placing
      them in a stable, denatured state.
AB  - Due to the high occurrence rate of overextension injuries to tendons and
      ligaments, it is important to understand the fundamental mechanisms of damage to
      these tissues' primary load-bearing elements: collagen fibrils and their
      constituent molecules. Based on our recent observations of a new subrupture,
      overload-induced mode of fibril disruption that we call discrete plasticity, we
      have sought in the current study to re-explore whether the tensile overload of
      collagen fibrils can alter the helical conformation of collagen molecules. In
      order to accomplish this, we have analyzed the conformation of collagen molecules
      within repeatedly overloaded tendons in relation to their undamaged matched-pair
      controls using both differential scanning calorimetry and variable temperature
      trypsin digestion susceptibility. We find that tensile overload reduces the
      specific enthalpy of denaturation of tendons, and increases their susceptibility
      to trypsin digestion, even when the digestion is carried out at temperatures as
      low as 4  degrees C. Our results indicate that the tensile overload of collagen
      fibrils can uncoil the helix of collagen molecules, placing them in a stable,
      denatured state.

PMID- 23880370
TI  - Reconstitution of CKMT1 expression fails to rescue cells from mitochondrial
      membrane potential dissipation: implications for controlling RNAi experiments.
AB  - RNA interference (RNAi) is an essential method in molecular biology to reduce the
      expression of target genes and thereby determine their function. Since this tool
      is known to also have unspecific effects, control experiments are needed, chiefly
      among them the exclusion of off-target effects and the reconstitution of the
      genes' expression for the rescue of the cellular RNAi effects. We show here that
      the knock-down of the mitochondrial creatine kinase-1 (CKMT1) by RNA interference
      causes the dissipation of the mitochondrial membrane potential DeltaPsim. This
      was accomplished with 11 different RNAi constructs designed to target 7 distinct
      exons as well as exon/intron junctions making unspecific off-target effects
      unlikely. However, all our attempts failed to rescue human cells from DeltaPsim
      dissipation by the expression of CKMT1 alleles not targeted by RNAi. This
      included the transient and stable expression of the murine CKMT1 homologue, the
      expression of human codon usage-modified alleles, the transfection of a novel
      splice-isoform of CKMT1, and even the introduction of a human genomic clone for
      CKMT1 with codon usage changes. Our results indicate that while off-target
      effects of RNA interference can easily be addressed, the rescue of the knock-down
      phenotype is not necessarily achievable. 

PMID- 23880371
TI  - Activation of STAT3 is involved in neuroprotection by electroacupuncture
      pretreatment via cannabinoid CB1 receptors in rats.
AB  - Pretreatment with electroacupuncture (EA) attenuates cerebral ischemic injury
      through the endocannabinoid system, although the molecular mechanisms mediate
      this neuroprotection are unknown. It is well-known that signal transducer and
      activator of transcription 3 (STAT3) plays an essential role in cell survival and
      proliferation. Therefore, we investigated whether STAT3 is involved in EA
      pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after
      transient focal cerebral ischemia in rats. Two hours after EA pretreatment, focal
      cerebral ischemia was induced by middle cerebral artery occlusion (MACO) for 120
      min. The expression of pSTAT3(Ser727), which is necessary for STAT3 activation,
      was examined in the ipsilateral ischemic penumbra. Infarct volumes and
      neurological scores were evaluated at 72 h after MACO in the presence or absence
      of the STAT3 inhibitor peptide (PpYLKTK). Neuronal apoptosis and the Bax/Bcl-2
      ratio were also evaluated 24h after reperfusion. Our results showed that EA
      pretreatment significantly enhanced neuronal expression of pSTAT3(Ser727) in the
      ischemic penumbra 6h after reperfusion. Moreover, EA pretreatment reduced infarct
      volume, improved neurological outcome, inhibited neuronal apoptosis and decreased
      the Bax/Bcl-2 ratio following reperfusion. The beneficial effects of EA were
      attenuated by PpYLKTK administered 30 min before MACO, and PpYLKTK effectively
      reversed the increase in pSTAT3(Ser727) expression. Furthermore, CB1R antagonist
      or CB1R knockdown with siRNA blocked the elevation of pSTAT3(Ser727) expression
      by EA pretreatment, whereas the two CB1R agonists increased STAT3 activation. In
      conclusion, EA pretreatment enhances STAT3 activation via CB1R to protect against
      cerebral ischemia, suggesting that STAT3 activation may be a novel target for
      stroke intervention.

PMID- 23880373
TI  - Neural effects of prolonged mental fatigue: a magnetoencephalography study.
AB  - Mental fatigue, manifest as a reduced efficiency for mental work load, is
      prevalent in modern society. It is important to understand the neural mechanisms
      of mental fatigue and to develop appropriate methods for evaluating mental
      fatigue. In this study we quantified the effect of a long-duration mental fatigue
      inducing task on neural activity. We used magnetoencephalography (MEG) to examine
      the time course change of neural activity over the long duration of the task
      trials. Nine healthy male volunteers participated in this study. They performed
      two mental fatigue-inducing tasks on separate days. The order of task
      presentation was randomized in a single-blinded, crossover fashion. Each task
      consisted of 25-min mental fatigue-inducing 0- or 2-back task session for three
      times. Subjective rating of mental fatigue sensation and electrocardiogram, and
      resting state MEG measurements were performed just before and after each task
      session. MEG data were analyzed using narrow-band adaptive spatial filtering
      methods. Alpha band (8-13 Hz) power in the visual cortex decreased after
      performing the mental fatigue-inducing tasks, and the decrease of alpha power was
      greater when they performed 2-back task trials. The decrease in alpha power was
      positively associated with the self-reported level of mental fatigue sensation
      and sympathetic nerve activity level. These results demonstrate that performing
      the prolonged mental fatigue-inducing task causes overactivation of the visual
      cortex, manifest as decreased alpha power in this brain region. Our results
      increase understanding of the neural mechanisms of mental fatigue and can be used
      to develop new quantitative methods to assess mental fatigue.

PMID- 23880372
TI  - Central 5-alpha reduction of testosterone is required for testosterone's
      inhibition of the hypothalamo-pituitary-adrenal axis response to restraint stress
      in adult male rats.
AB  - In rodents, the hypothalamo-pituitary-adrenal (HPA) axis is controlled by a
      precise regulatory mechanism that is influenced by circulating gonadal and
      adrenal hormones. In males, gonadectomy increases the adrenocorticotropic hormone
      (ACTH) and corticosterone (CORT) response to stressors, and androgen replacement
      returns the response to that of the intact male. Testosterone (T) actions in
      regulating HPA activity may be through aromatization to estradiol, or by 5alpha
      reduction to the more potent androgen, dihydrotestosterone (DHT). To determine if
      the latter pathway is involved, we assessed the function of the HPA axis response
      to restraint stress following hormone treatments, or after peripheral or central
      treatment with the 5alpha-reductase inhibitor, finasteride. Initially, we
      examined the timecourse whereby gonadectomy alters the CORT response to restraint
      stress. Enhanced CORT responses were evident within 48 h following gonadectomy.
      Correspondingly, treatment of intact male rats with the 5alpha-reductase
      inhibitor, finasteride, for 48 h, enhanced the CORT and ACTH response to
      restraint stress. Peripheral injections of gonadectomized male rats with DHT or T
      for 48 h reduced the ACTH and CORT response to restraint stress. The effects of
      T, but not DHT, could be blocked by the third ventricle administration of
      finasteride prior to stress application. These data indicate that the actions of
      T in modulating HPA axis activity involve 5alpha-reductase within the central
      nervous system. These results further our understanding of how T acts to modulate
      the neuroendocrine stress responses and indicate that 5alpha reduction to DHT is
      a necessary step for T action.

PMID- 23880374
TI  - Joint graph cut and relative fuzzy connectedness image segmentation algorithm.
AB  - We introduce an image segmentation algorithm, called GC(sum)(max), which
      combines, in novel manner, the strengths of two popular algorithms: Relative
      Fuzzy Connectedness (RFC) and (standard) Graph Cut (GC). We show, both
      theoretically and experimentally, that GC(sum)(max) preserves robustness of RFC
      with respect to the seed choice (thus, avoiding "shrinking problem" of GC), while
      keeping GC's stronger control over the problem of "leaking though poorly defined
      boundary segments." The analysis of GC(sum)(max) is greatly facilitated by our
      recent theoretical results that RFC can be described within the framework of
      Generalized GC (GGC) segmentation algorithms. In our implementation of
      GC(sum)(max) we use, as a subroutine, a version of RFC algorithm (based on Image
      Forest Transform) that runs (provably) in linear time with respect to the image
      size. This results in GC(sum)(max) running in a time close to linear.
      Experimental comparison of GC(sum)(max) to GC, an iterative version of RFC
      (IRFC), and power watershed (PW), based on a variety medical and non-medical
      images, indicates superior accuracy performance of GC(sum)(max) over these other
      methods, resulting in a rank ordering of GC(sum)(max)>PW~IRFC>GC.

PMID- 23880375
TI  - Automated drusen segmentation and quantification in SD-OCT images.
AB  - Spectral domain optical coherence tomography (SD-OCT) is a useful tool for the
      visualization of drusen, a retinal abnormality seen in patients with age-related
      macular degeneration (AMD); however, objective assessment of drusen is thwarted
      by the lack of a method to robustly quantify these lesions on serial OCT images.
      Here, we describe an automatic drusen segmentation method for SD-OCT retinal
      images, which leverages a priori knowledge of normal retinal morphology and
      anatomical features. The highly reflective and locally connected pixels located
      below the retinal nerve fiber layer (RNFL) are used to generate a segmentation of
      the retinal pigment epithelium (RPE) layer. The observed and expected contours of
      the RPE layer are obtained by interpolating and fitting the shape of the
      segmented RPE layer, respectively. The areas located between the interpolated and
      fitted RPE shapes (which have nonzero area when drusen occurs) are marked as
      drusen. To enhance drusen quantification, we also developed a novel method of
      retinal projection to generate an en face retinal image based on the RPE
      extraction, which improves the quality of drusen visualization over the current
      approach to producing retinal projections from SD-OCT images based on a summed
      voxel projection (SVP), and it provides a means of obtaining quantitative
      features of drusen in the en face projection. Visualization of the segmented
      drusen is refined through several post-processing steps, drusen detection to
      eliminate false positive detections on consecutive slices, drusen refinement on a
      projection view of drusen, and drusen smoothing. Experimental evaluation results
      demonstrate that our method is effective for drusen segmentation. In a
      preliminary analysis of the potential clinical utility of our methods,
      quantitative drusen measurements, such as area and volume, can be correlated with
      the drusen progression in non-exudative AMD, suggesting that our approach may
      produce useful quantitative imaging biomarkers to follow this disease and predict
      patient outcome. 

PMID- 23880376
TI  - Specificity, promiscuity, and precursor frequency in immunoreceptors.
AB  - The immune system is comprised of various immune cell populations that utilize a
      spectrum of immunoreceptors characterized by different levels of specificity,
      diversity, and prevalence within a host and across a population. These range from
      the universal receptors employed by both innate cells and innate-like cells, such
      as NKT and MAIT cells, through to receptors expressed on T cells with sporadic
      incidence. Here we review recent advances in understanding the molecular
      mechanisms that drive the observed spectra of T cell receptors in vivo. 

PMID- 23880377
TI  - Identifying a standard set of outcome parameters for the evaluation of
      orthogeriatric co-management for hip fractures.
AB  - BACKGROUND AND PURPOSE: Osteoporotic fractures are an increasing problem in the
      world due to the ageing of the population. Different models of orthogeriatric co
      management are currently in use worldwide. These models differ for instance by
      the health-care professional who has the responsibility for care in the acute and
      early rehabilitation phases. There is no international consensus regarding the
      best model of care and which outcome parameters should be used to evaluate these
      models. The goal of this project was to identify which outcome parameters and
      assessment tools should be used to measure and compare outcome changes that can
      be made by the implementation of orthogeriatric co-management models and to
      develop recommendations about how and when these outcome parameters should be
      measured. It was not the purpose of this study to describe items that might have
      an impact on the outcome but cannot be influenced such as age, co-morbidities and
      cognitive impairment at admission. METHODS: Based on a review of the literature
      on existing orthogeriatric co-management evaluation studies, 14 outcome
      parameters were evaluated and discussed in a 2-day meeting with panellists. These
      panellists were selected based on research and/or clinical expertise in hip
      fracture management and a common interest in measuring outcome in hip fracture
      care. RESULTS: We defined 12 objective and subjective outcome parameters and how
      they should be measured: mortality, length of stay, time to surgery,
      complications, re-admission rate, mobility, quality of life, pain, activities of
      daily living, medication use, place of residence and costs. We could not
      recommend an appropriate tool to measure patients' satisfaction and falls. We
      defined the time points at which these outcome parameters should be collected to
      be at admission and discharge, 30 days, 90 days and 1 year after admission.
      CONCLUSION: Twelve objective and patient-reported outcome parameters were
      selected to form a standard set for the measurement of influenceable outcome of
      patients treated in different models of orthogeriatric co-managed care.

PMID- 23880378
TI  - The serotonin transporter linked polymorphic region and brain-derived
      neurotrophic factor valine to methionine at position 66 polymorphisms and
      maternal history of depression: associations with cognitive vulnerability to
      depression in childhood.
AB  - Preliminary work indicates that cognitive vulnerability to depression may be
      associated with variants of the serotonin transporter promoter polymorphism (5
      HTTLPR) and the valine to methionine at position 66 (val66met) polymorphism of
      the brain-derived neurotrophic factor (BDNF) gene; however, existing reports come
      from small samples. The present study sought to replicate and extend this
      research in a sample of 375 community-dwelling children and their parents.
      Following a negative mood induction, children completed a self-referent encoding
      task tapping memory for positive and negative self-descriptive traits. Consistent
      with previous work, we found that children with at least one short variant of the
      5-HTTLPR had enhanced memory for negative self-descriptive traits. The BDNF
      val66met polymorphism had no main effect but was moderated by maternal
      depression, such that children with a BDNF methionine allele had a heightened
      memory for negative self-descriptive traits when mothers had experienced
      depression during children's lifetimes; in contrast, children with a methionine
      allele had low recall of negative traits when mothers had no depression history.
      The findings provide further support for the notion that the 5-HTTLPR is
      associated with cognitive markers of depression vulnerability and that the BDNF
      methionine allele moderates children's sensitivity to contextual factors. 

PMID- 23880380
TI  - Longitudinal relations between sectarian and nonsectarian community violence and
      child adjustment in Northern Ireland.
AB  - Although relations between political violence and child adjustment are well
      documented, longitudinal research is needed to adequately address the many
      questions remaining about the contexts and developmental trajectories underlying
      the effects on children in areas of political violence. The study examined the
      relations between sectarian and nonsectarian community violence and adolescent
      adjustment problems over 4 consecutive years. Participants included 999 mother
      child dyads (482 boys, 517 girls), M ages = 12.18 (SD = 1.82), 13.24 (SD = 1.83),
      13.61 (SD = 1.99), and 14.66 (SD = 1.96) years, respectively, living in socially
      deprived neighborhoods in Belfast, Northern Ireland, a context of historical and
      ongoing political violence. In examining trajectories of adjustment problems,
      including youth experience with both sectarian and nonsectarian antisocial
      behaviors, sectarian antisocial behavior significantly predicted more adjustment
      problems across the 4 years of the study. Experiencing sectarian antisocial
      behavior was related to increased adolescent adjustment problems, and this
      relationship was accentuated in neighborhoods characterized by higher crime
      rates. The discussion considers the implications for further validating the
      distinction between sectarian and nonsectarian violence, including consideration
      of neighborhood crime levels, from the child's perspective in a setting of
      political violence. 

PMID- 23880379
TI  - Vulnerability to depression: a moderated mediation model of the roles of child
      maltreatment, peer victimization, and serotonin transporter linked polymorphic
      region genetic variation among children from low socioeconomic status
      backgrounds.
AB  - Child maltreatment, peer victimization, and a polymorphism of the serotonin
      transporter gene (5-HTTLPR) were examined as predictors of depressive
      symptomatology. Children (M age = 11.26, SD = 1.65), including 156 maltreated and
      145 nonmaltreated children from comparable low socioeconomic backgrounds,
      provided DNA samples and self-reports of relational peer victimization, overt
      peer victimization, and depressive symptoms. Path analysis showed that relational
      and overt victimization mediated the association between child maltreatment and
      depressive symptoms. Bootstrapping procedures were used to test moderated
      mediation and demonstrated that genotype moderated the indirect effects of
      relational and overt victimization on child depressive symptoms, such that
      victimized children with the long/long variation were at an increased risk for
      depressive symptoms compared to victimized children carrying a short allele.
      Results highlight the utility of examining process models that incorporate
      biological and psychological factors contributing to the development of
      depressive symptomatology and provide direction toward understanding and
      promoting resilience among high-risk youth from a multiple levels of analysis
      approach. 

PMID- 23880381
TI  - Are flatter diurnal cortisol rhythms associated with major depression and anxiety
      disorders in late adolescence? The role of life stress and daily negative
      emotion.
AB  - Alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning have been
      associated with major depression disorder (MDD) and some anxiety disorders. Few
      researchers have tested the possibility that high levels of recent life stress or
      elevations in negative emotion may partially account for the HPA axis alterations
      observed in these disorders. In a sample of 300 adolescents from the Youth
      Emotion Project, we examined associations between MDD and anxiety disorders,
      dimensional measures of internalizing symptomatology, life stress, mood on the
      days of cortisol testing, and HPA axis functioning. Adolescents with a past MDD
      episode and those with a recent MDD episode comorbid with an anxiety disorder had
      flatter diurnal cortisol slopes than adolescents without a history of
      internalizing disorders. Higher reports of general distress, a dimension of
      internalizing symptomatology, were also associated with flatter slopes. Negative
      emotion, specifically sadness and loneliness, was associated with flatter slopes
      and partially accounted for the associations between comorbid MDD and anxiety
      disorders and cortisol. The associations between past MDD and cortisol slopes
      were not accounted for by negative emotion, dimensional variation in
      internalizing symptomatology, or levels of life stress, indicating that flatter
      cortisol slopes may also be a "scar" marker of past experiences of MDD. 

PMID- 23880382
TI  - Interests in high-functioning autism are more intense, interfering, and
      idiosyncratic than those in neurotypical development.
AB  - Although circumscribed interests are pathognomonic with autism, much about these
      interests remains unknown. Using the Interests Scale (IS), this study compares
      interests between 76 neurotypical (NT) individuals and 109 individuals with high
      functioning autism spectrum disorder (HF-ASD) matched groupwise on age, IQ, and
      gender ratio. Participants and their parents/caregivers completed diagnostic
      measures (the Autism Diagnostic Interview-Revised and the Autism Diagnostic
      Observation Schedule; HF-ASD only), cognitive tests (Wechsler IQ Scales), and
      questionnaires (the Repetitive Behavior Scale-Revised, the Behavior Rating
      Inventory of Executive Function, and the Social Responsiveness Scale), in
      addition to the IS. Consistent with previous research, HF-ASD and NT individuals
      did not differ in number of interest areas, but the types of interests and
      intensity of those interests differed considerably. Using only the IS intensity
      score, 81% of individuals were correctly classified (NT or HF-ASD) in a logistic
      regression analysis. Among individuals with HF-ASD, Interests Scale scores were
      significantly related to Autism Diagnostic Observation Schedule, Behavior Rating
      Inventory of Executive Function, Repetitive Behavior Scale-Revised, and Social
      Responsiveness Scale scores, but they were not related to Autism Diagnostic
      Interview-Revised scores, IQ, gender, age, or psychotropic medication use. The
      type and intensity, but not the number, of interests distinguish high-functioning
      individuals with ASD from NT individuals. 

PMID- 23880384
TI  - Strategic objectives for improving understanding of informant discrepancies in
      developmental psychopathology research.
AB  - Developmental psychopathology researchers and practitioners commonly conduct
      behavioral assessments using multiple informants' reports (e.g., parents,
      teachers, practitioners, children, and laboratory observers). These assessments
      often yield inconsistent conclusions about important questions in developmental
      psychopathology research, depending on the informant (e.g., psychiatric diagnoses
      and risk factors of disorder). Researchers have theorized why informant
      discrepancies exist and advanced methodological models of informant
      discrepancies. However, over 50 years of empirical data has uncovered little
      knowledge about these discrepancies beyond that they exist, complicate
      interpretations of research findings and assessment outcomes in practice, and
      correlate with some characteristics of the informants providing reports (e.g.,
      demographics and mood levels). Further, recent studies often yield take-home
      messages about the importance of taking a multi-informant approach to clinical
      and developmental assessments. Researchers draw these conclusions from their
      work, despite multi-informant approaches to assessment long being a part of best
      practices in clinical and developmental assessments. Consequently, developmental
      psychopathology researchers and practitioners are in dire need of a focused set
      of research priorities with the key goal of rapidly advancing knowledge about
      informant discrepancies. In this paper, I discuss these research priorities,
      review work indicating the feasibility of conducting research addressing these
      priorities, and specify what researchers and practitioners would gain from
      studies advancing knowledge about informant discrepancies in developmental
      psychopathology research. 

PMID- 23880383
TI  - Predicting internalizing problems in Chinese children: the unique and interactive
      effects of parenting and child temperament.
AB  - The additive and interactive relations of parenting styles (authoritative and
      authoritarian parenting) and child temperament (anger/frustration, sadness, and
      effortful control) to children's internalizing problems were examined in a 3.8
      year longitudinal study of 425 Chinese children (aged 6-9 years) from Beijing. At
      Wave 1, parents self-reported on their parenting styles, and parents and teachers
      rated child temperament. At Wave 2, parents, teachers, and children rated
      children's internalizing problems. Structural equation modeling indicated that
      the main effect of authoritative parenting and the interactions of Authoritarian
      Parenting * Effortful Control and Authoritative Parenting * Anger/Frustration
      (parents' reports only) prospectively and uniquely predicted internalizing
      problems. The above results did not vary by child sex and remained significant
      after controlling for co-occurring externalizing problems. These findings suggest
      that (a) children with low effortful control may be particularly susceptible to
      the adverse effect of authoritarian parenting and (b) the benefit of
      authoritative parenting may be especially important for children with high
      anger/frustration. 

PMID- 23880385
TI  - Dynamic temporal relations between anxious and depressive symptoms across
      adolescence.
AB  - Symptoms of anxiety and depression are prevalent among adolescents and associated
      with impairment in multiple domains of functioning. Moreover, anxiety and
      depression frequently co-occur, with estimated comorbidity rates as high as 75%.
      Whereas previous research has shown that anxiety symptoms predict increased
      depressive symptoms over time, the relation between depressive symptoms and later
      anxiety symptoms has been inconsistent. The present study examined dynamic
      relations between anxiety and depressive symptoms across adolescence and explored
      whether these longitudinal relations were moderated by maternal history of
      anxiety, family relationship quality, or children's attributional style.
      Participants included 240 children (M age = 11.86 years; 53.9% female) and their
      mothers, who were assessed annually for 6 years. Children reported on their
      depressive symptoms and mothers reported on their child's anxiety symptoms.
      Dynamic latent change score models indicated that anxiety symptoms predicted
      subsequent elevations in depressive symptoms over time. Depressive symptoms
      predicted subsequent elevations in anxiety symptoms among children who had
      mothers with a history of anxiety, reported low family relationship quality, or
      had high levels of negative attributions. Thus, whereas anxiety symptoms were a
      robust predictor of later depressive symptoms during adolescence, contextual and
      individual factors may be important to consider when examining relations between
      depressive symptoms and subsequent change in anxiety symptoms. 

PMID- 23880386
TI  - Effects of family cohesion and heart rate reactivity on aggressive/rule-breaking
      behavior and prosocial behavior in adolescence: the Tracking Adolescents'
      Individual Lives Survey study.
AB  - The biological sensitivity to context hypothesis posits that high physiological
      reactivity (i.e., increases in arousal from baseline) constitutes heightened
      sensitivity to environmental influences, for better or worse. To test this
      hypothesis, we examined the interactive effects of family cohesion and heart rate
      reactivity to a public speaking task on aggressive/rule-breaking and prosocial
      behavior in a large sample of adolescents (N = 679; M age = 16.14). Multivariate
      analyses revealed small- to medium-sized main effects of lower family cohesion
      and lower heart rate reactivity on higher levels of aggressive/rule-breaking and
      lower levels of prosocial behavior. Although there was some evidence of three-way
      interactions among family cohesion, heart rate reactivity, and sex in predicting
      these outcome variables, these interactions were not in the direction predicted
      by the biological sensitivity to context hypothesis. Instead, heightened
      reactivity appeared to operate as a protective factor against family adversity,
      rather than as a susceptibility factor. The results of the present study raise
      the possibility that stress reactivity may no longer operate as a mechanism of
      differential susceptibility in adolescence. 

PMID- 23880387
TI  - Maturity and change in personality: developmental trends of temperament and
      character in adulthood.
AB  - We studied the developmental trends of temperament and character in a
      longitudinal population-based sample of Finnish men and women aged 20-45 years
      using the Temperament and Character Inventory model of personality. Personality
      was assessed in 1997, 2001, and 2007 (n = 2,104, 2,095, and 2,056, respectively).
      Mean-level changes demonstrated qualitatively distinct developmental patterns for
      character (self-directedness, cooperativeness, and self-transcendence) and
      temperament (novelty seeking, harm avoidance, reward dependence, and
      persistence). Character developed toward greater maturity, although self
      transcendence decreased with age. However, self-transcendence was the strongest
      predictor of overall personality change. Cohort effects indicated lower level of
      self-transcendence and higher level of self-directedness and cooperativeness in
      younger birth cohorts. Regarding temperament, novelty seeking decreased and
      persistence increased slightly with age. Both high novelty seeking and high
      persistence predicted overall personality change. These findings suggest that
      temperament and character traits follow different kinds of developmental
      trajectories. 

PMID- 23880388
TI  - A theoretical model of continuity in anxiety and links to academic achievement in
      disaster-exposed school children.
AB  - This study tested a theoretical model of continuity in anxious emotion and its
      links to academic achievement in disaster-exposed youth. An urban school based
      sample of youths (n = 191; Grades 4-8) exposed to Hurricane Katrina were assessed
      at 24 months (Time 1) and then again at 30 months (Time 2) postdisaster. Academic
      achievement was assessed through end of the school year standardized test scores
      (~31 months after Katrina). The results suggest that the association of traumatic
      stress to academic achievement was indirect via linkages from earlier (Time 1)
      posttraumatic stress disorder symptoms that predicted later (Time 2) test
      anxiety. Time 2 test anxiety was then negatively associated with academic
      achievement. Age and gender invariance testing suggested strong consistency
      across gender and minor developmental variation in the age range examined. The
      model presented advances the developmental understanding of the expression of
      anxious emotion and its links to student achievement among disaster-exposed urban
      school children. The findings highlight the importance of identifying heterotypic
      continuity in anxiety and suggest potential applied and policy directions for
      disaster-exposed youth. Avenues for future theoretical refinement are also
      discussed. 

PMID- 23880389
TI  - Escaping the snare of chronological growth and launching a free curve
      alternative: general deviance as latent growth model.
AB  - Researchers studying longitudinal relationships among multiple problem behaviors
      sometimes characterize autoregressive relationships across constructs as
      indicating "protective" or "launch" factors or as "developmental snares." These
      terms are used to indicate that initial or intermediary states of one problem
      behavior subsequently inhibit or promote some other problem behavior. Such models
      are contrasted with models of "general deviance" over time in which all problem
      behaviors are viewed as indicators of a common linear trajectory. When fit of the
      "general deviance" model is poor and fit of one or more autoregressive models is
      good, this is taken as support for the inhibitory or enhancing effect of one
      construct on another. In this paper, we argue that researchers consider competing
      models of growth before comparing deviance and time-bound models. Specifically,
      we propose use of the free curve slope intercept (FCSI) growth model (Meredith &
      Tisak, 1990) as a general model to typify change in a construct over time. The
      FCSI model includes, as nested special cases, several statistical models often
      used for prospective data, such as linear slope intercept models, repeated
      measures multivariate analysis of variance, various one-factor models, and
      hierarchical linear models. When considering models involving multiple
      constructs, we argue the construct of "general deviance" can be expressed as a
      single-trait multimethod model, permitting a characterization of the deviance
      construct over time without requiring restrictive assumptions about the form of
      growth over time. As an example, prospective assessments of problem behaviors
      from the Dunedin Multidisciplinary Health and Development Study (Silva & Stanton,
      1996) are considered and contrasted with earlier analyses of Hussong, Curran,
      Moffitt, and Caspi (2008), which supported launch and snare hypotheses. For
      antisocial behavior, the FCSI model fit better than other models, including the
      linear chronometric growth curve model used by Hussong et al. For models
      including multiple constructs, a general deviance model involving a single trait
      and multimethod factors (or a corresponding hierarchical factor model) fit the
      data better than either the "snares" alternatives or the general deviance model
      previously considered by Hussong et al. Taken together, the analyses support the
      view that linkages and turning points cannot be contrasted with general deviance
      models absent additional experimental intervention or control. 

PMID- 23880390
TI  - Contextual risk and promotive processes in Puerto Rican youths' internalizing
      trajectories in Puerto Rico and New York.
AB  - Research on ethnic-minority youths' mental health has rarely examined
      developmental trajectories for the same ethnic group in contexts where they are a
      minority versus where they are the majority or mechanisms accounting for
      differences in trajectories across such contexts. This study examines Puerto
      Rican youth residing in two contexts, one in which they are in their home culture
      of Puerto Rico and one in which they are a minority group, in New York. We
      explore the relationship among social context, minority status, risk, resilience,
      and trajectories of internalizing symptoms after adjusting for factors related to
      migration. We found that youths' reports of internalizing symptoms declined over
      time. Youths in New York had higher levels of internalizing symptoms than did
      youths in Puerto Rico, but they had similar trajectories. Differences in
      internalizing symptoms across the two social contexts were accounted for by
      experiences of discrimination and exposure to violence. Parental monitoring was
      associated with fewer internalizing symptoms across the two sites, although this
      effect diminished over time. Contrary to what was expected, family religiosity
      was associated with higher levels of internalizing symptoms. This association was
      stronger in New York than in the Puerto Rico site. 

PMID- 23880391
TI  - Restricted and repetitive behaviors in autism spectrum disorders: the
      relationship of attention and motor deficits.
AB  - Restricted and repetitive behaviors (RRBs) are hallmark symptoms of autism
      spectrum disorders (ASDs); however, it has proven difficult to understand the
      mechanisms underlying these behaviors. One hypothesis suggests that RRBs are the
      result of a core deficit in attention. Alternatively, abnormalities of the motor
      system may constitute the central mechanism underlying RRBs, given motor deficits
      observed in ASDs. In this experiment, we investigated the etiology of RRBs and
      the relationship between attention and motor deficits. Movement impairments (a)
      may be indirectly related to attention deficits, (b) may result from a shared
      compromised process, or (c) may be independent. Twenty-two adolescents with ASD
      and 20 typically developing participants performed a spatial attention task.
      Movement impairments were assessed with a rhythmic tapping task. Attentional
      orienting and motor control were found to be related and supported the hypothesis
      that these impairments in ASD arise from a shared process. In contrast, measures
      of attention switching and motor control were found to be independent.
      Stereotyped behaviors, as assessed by parental ratings, were related more to the
      degree of motor impairment than to deficits of attention. These results suggest
      that both attentional orienting deficits and stereotyped RRBs are related to a
      compromised motor system. 

PMID- 23880393
TI  - Relational aggression, victimization, and adjustment during middle childhood.
AB  - A secondary analysis of the National Institute of Child Health and Human
      Development Study of Early Child Care and Youth Development was conducted to test
      the mechanisms by which relational aggression in third grade was associated both
      directly and indirectly with relational victimization in sixth grade. A large
      sample (N = 1,035; 522 girls; M = 8.3 years old; SD = 0.23) and multiple
      informants (teacher, child, and parent report) and methods were used to test
      several theoretically driven hypotheses. Our path analysis model suggested
      evidence for both direct and indirect pathways consistent with the sequential
      social process model of peer harassment. Relational aggression was significantly
      associated with future relational victimization even after controlling for
      physical aggression and gender. Loneliness mediated the direct association
      between relational aggression and peer victimization. A second model testing the
      reverse direction of effect revealed that relational victimization in third grade
      predicted relational aggression in sixth grade and was associated with loneliness
      and depressive symptoms in fifth grade, but there was no evidence for any of the
      indirect pathways. 

PMID- 23880392
TI  - Prospective developmental subtypes of alcohol dependence from age 18 to 32 years:
      implications for nosology, etiology, and intervention.
AB  - The purpose of the present study is to identify child and adult correlates that
      differentiate (a) individuals with persistent alcohol dependence from individuals
      with developmentally limited alcohol dependence and (b) individuals with adult
      onset alcohol dependence from individuals who never diagnose. There are 1,037
      members of the Dunedin Longitudinal Study, which is a birth cohort followed
      prospectively from birth until age 32. Past-year DSM-IV alcohol dependence
      diagnoses are ascertained with structured diagnostic interviews at ages 18, 21,
      26, and 32. Individuals are classified as developmentally limited, persistent, or
      adult-onset subtypes based on their time-ordered pattern of diagnoses. The
      persistent subtype generally exhibits the worst scores on all correlates,
      including family psychiatric history, adolescent and adult externalizing and
      internalizing problems, adolescent and adult substance use, adult quality of
      life, and coping strategies. The prospective predictors that distinguished them
      from the developmentally limited subtype involved family liability, adolescent
      negative affectivity, daily alcohol use, and frequent marijuana use. Furthermore,
      young people who develop the persistent subtype of alcohol dependence are
      distinguished from the developmentally limited subtype by an inability to reduce
      drinking and by continued use despite problems by age 18. The adult-onset group
      members are virtually indistinguishable from ordinary cohort members as children
      or adolescents; however, in adulthood, adult-onset cases are distinguished by
      problems with depression, substance use, stress, and strategies for coping with
      stress. Information about age of onset and developmental course is fundamental
      for identifying subtypes of alcohol dependence. Subtype-specific etiologies point
      to targeted prevention and intervention efforts based on the characteristics of
      each subtype. 

PMID- 23880394
TI  - Deconstructing the externalizing spectrum: growth patterns of overt aggression,
      covert aggression, oppositional behavior, impulsivity/inattention, and emotion
      dysregulation between school entry and early adolescence.
AB  - The purpose of this study was to determine whether five subcomponents of
      children's externalizing behavior showed distinctive patterns of long-term growth
      and predictive correlates. We examined growth in teachers' ratings of overt
      aggression, covert aggression, oppositional defiance, impulsivity/inattention,
      and emotion dysregulation across three developmental periods spanning
      kindergarten through Grade 8 (ages 5-13 years). We also determined whether three
      salient background characteristics, family socioeconomic status, child ethnicity,
      and child gender, differentially predicted growth in discrete categories of child
      externalizing symptoms across development. Participants were 543 kindergarten-age
      children (52% male, 81% European American, 17% African American) whose problem
      behaviors were rated by teachers each successive year of development through
      Grade 8. Latent growth curve analyses were performed for each component scale,
      contrasting with overall externalizing, in a piecewise fashion encompassing three
      developmental periods: kindergarten-Grade 2, Grades 3-5, and Grades 6-8. We found
      that most subconstructs of externalizing behavior increased significantly across
      the early school age period relative to middle childhood and early adolescence.
      However, overt aggression did not show early positive growth, and emotion
      dysregulation significantly increased across middle childhood. Advantages of
      using subscales were most clear in relation to illustrating different growth
      functions between the discrete developmental periods. Moreover, growth in some
      discrete subcomponents was differentially associated with variations in family
      socioeconomic status and ethnicity. Our findings strongly affirmed the necessity
      of adopting a developmental approach to the analysis of growth in children's
      externalizing behavior and provided unique data concerning similarities and
      differences in growth between subconstructs of child and adolescent externalizing
      behavior. 

PMID- 23880395
TI  - The distinctive role of romantic relationships in moderating the effects of early
      caregiving on adult anxious-depressed symptoms over 9 years.
AB  - This study tests a model of young adult romantic quality as a moderator of the
      effects of early caregiving on anxious-depressed symptoms over a 9-year period in
      adulthood. Participants (n = 93) were a subsample from a longitudinal study of
      risk and adaptation. Quality of early caregiving was measured using observational
      data collected at five points in the first 4 years of life. Young adult romantic
      relationship quality was assessed from interviews with participants at age 23.
      Self-report anxious-depressed symptoms were measured at ages 23, 26, and 32. The
      results indicated that romantic quality moderated early caregiving to predict
      symptom levels across this period, with evidence for inoculation, amplification,
      and compensation effects. A discriminant analysis examining young adult work
      competence as a moderator provided further evidence for the distinctiveness of
      romantic relationships in changing the association between early caregiving and
      adult internalizing symptoms. 

PMID- 23880396
TI  - Language and internalizing and externalizing behavioral adjustment: developmental
      pathways from childhood to adolescence.
AB  - Two independent prospective longitudinal studies that cumulatively spanned the
      age interval from 4 years to 14 years used multiwave designs to investigate
      developmental associations between language and behavioral adjustment
      (internalizing and externalizing behavior problems). Altogether 224 children,
      their mothers, and teachers provided data. Series of nested path analysis models
      were used to determine the most parsimonious and plausible paths among the three
      constructs over and above stability in each across age and their covariation at
      each age. In both studies, children with poorer language skills in early
      childhood had more internalizing behavior problems in later childhood and in
      early adolescence. These developmental paths between language and behavioral
      adjustment held after taking into consideration children's nonverbal intellectual
      functioning, maternal verbal intelligence, education, parenting knowledge, and
      social desirability bias, as well as family socioeconomic status, and they
      applied equally to girls and boys. 

PMID- 23880397
TI  - Ferric citrate decreases ruminal hydrogen sulphide concentrations in feedlot
      cattle fed diets high in sulphate.
AB  - Dissimilatory reduction of sulphate by sulphate-reducing bacteria in the rumen
      produces sulphide, which can lead to a build-up of the toxic gas hydrogen
      sulphide (H2S) in the rumen when increased concentrations of sulphate are
      consumed by ruminants. We hypothesised that adding ferric Fe would competitively
      inhibit ruminal sulphate reduction. The effects of five concentrations and two
      sources (ferric citrate or ferric ammonium citrate) of ferric Fe were examined in
      vitro (n 6 per treatment). Rumen fluid was collected from a steer that was
      adapted to a high-concentrate, high-sulphate diet (0.51 % S). The addition of
      either source of ferric Fe decreased (P< 0.01) H2S concentrations without
      affecting gas production (P= 0.38), fluid pH (P= 0.80) or in vitro DM
      digestibility (P= 0.38) after a 24 h incubation. An in vivo experiment was
      conducted using eight ruminally fistulated steers (543 (sem 12) kg) in a
      replicated Latin square with four periods and four treatments. The treatments
      included a high-concentrate, high-sulphate control diet (0.46 % S) or the control
      diet plus ferric ammonium citrate at concentrations of 200, 300 or 400 mg Fe/kg
      diet DM. The inclusion of ferric Fe did not affect DM intake (P= 0.21). There was
      a linear (P< 0.01) decrease in the concentration of ruminal H2S as the addition
      of ferric Fe concentrations increased. Ferric citrate appears to be an effective
      way to decrease ruminal H2S concentrations, which could allow producers to safely
      increase the inclusion of ethanol co-products. 

PMID- 23880398
TI  - Risk factors for the transmission of foot-and-mouth disease during the 2010
      outbreak in Japan: a case-control study.
AB  - BACKGROUND: In 2010, foot-and-mouth disease (FMD) occurred for the first time in
      a decade in Japan. Movement or shipment of people and animals around infected
      farms was restricted; however these contingency measures proved insufficient to
      prevent FMD spread. Consequently, a total of 292 farms were confirmed as infected
      during this outbreak. We conducted a case-control study to identify the risk
      factors associated with FMD transmission between farms during these restrictions.
      As there was discordance in the control measures taken, risk factors were
      examined separately for two areas. Analyses were also performed separately for
      cattle and pig farms given their different infectivity and susceptibility.
      RESULTS: For cattle farms in the movement restriction area, the odds of having
      the factor 'farm equipment was shared with other farms' was significantly higher
      for case farms than for control farms. For cattle farms in the shipment
      restriction area, the odds of having the factors 'feed transport vehicles visited
      the farm' and 'staff of livestock-related companies visited the farm' were
      significantly higher on case farms than control farms. In pig farms in the
      movement restriction area, the odds of having factor 'farm staff commuted from
      outside' was 20 times higher for case farms than control farms. In addition, case
      farms were less likely to have the factors 'fattening farm' and 'barn has
      physical barriers' compared with control farms. CONCLUSIONS: In the movement
      restriction area, the disease was likely to spread regardless of the movement of
      people and vehicles, and physical barriers were found to be a protective factor.
      Therefore, physical barriers from the surrounding environments seemed to prevent
      farms from being infected. Conversely, in the shipment restriction area, movement
      of people and vehicles was strongly associated with disease spread. These results
      allow a better understanding of the risk factors associated with FMD transmission
      and are useful to enhance future preventive measures against transmission during
      FMD outbreaks.

PMID- 23880399
TI  - Meaningful use: a roadmap for the advancement of health information exchange.
AB  - Frankel and colleagues have compared Israel and the U.S.'s experiences with
      health information exchange (HIE). They highlight the importance of institutional
      factors in fostering HIE development, notably the influence of local structures,
      experience and incentives. Historically, information infrastructure in the U.S.
      has been limited due to lack of standards, fragmented institutions and
      competition. The Health Information Technology for Economic and Clinical Health
      (HITECH) Act of 2009 authorized billions of dollars for the adoption and
      "Meaningful Use" of electronic health records. HITECH programs and Meaningful Use
      incentives target the advancement of HIE through 1) building blocks, 2) local
      support and 3) payment incentives. Meaningful Use requirements create a roadmap
      to broader electronic exchange of health information among providers and with
      patients. Ultimately, successful HIE in the U.S. will depend on whether
      Meaningful Use can address institutional needs within local markets.This is a
      commentary on http://www.ijhpr.org/content/2/1/722. 

PMID- 23880400
TI  - Spontaneous triple coronary artery dissection in a 78-year-old woman resolved
      angiographically with anticoagulation and medical management.
AB  - A 78-year-old woman who presented with chest pain, on a background of
      hypertension and varicose veins, was found to have a non-ST segment elevation
      myocardial infarction with coronary angiography demonstrating dissections of all
      three major arteries distally. She was treated medically, with anticoagulation
      and risk factor management as the primary therapies. This is the first reported
      case of triple spontaneous coronary artery dissection treated medically, along
      with angiographic follow-up demonstrating complete resolution. 

PMID- 23880402
TI  - Use of magnetic resonance arthrography to compare clinical features and
      structural integrity after arthroscopic repair of bursal versus articular side
      partial-thickness rotator cuff tears.
AB  - BACKGROUND: There has been no study using magnetic resonance arthrography (MRA)
      to compare clinical features and structural integrity after arthroscopic repair
      of bursal and articular side partial-thickness rotator cuff tears (PTRCTs).
      HYPOTHESIS: The 2 groups studied, which consisted of patients who underwent
      arthroscopic repair for either the articular side or the bursal side, would show
      significant improvement in overall outcomes after surgery, even though clinical
      outcomes and structural integrity would not be significantly different. It was
      thought that the incidence of preoperative positive impingement signs and
      protruded spurs on the acromion undersurface would be higher in patients with a
      bursal side tear. STUDY DESIGN: Case-control study; Level of evidence, 3.
      METHODS: The current study consisted of 83 patients who underwent arthroscopic
      repair for either articular side (group A; n = 29) or bursal side (group B; n =
      54) PTRCT and who were available at the 2-year follow-up. Clinical outcomes were
      compared by use of the Neer impingement sign, visual analog scale for pain,
      Simple Shoulder Test, University of California Los Angeles score, and American
      Shoulder and Elbow Surgeons score. At 6 months after surgery, MRA was used to
      assess structural integrity. RESULTS: At 2-year follow-up, both groups showed
      significant improvement in pain and shoulder function scores, even though there
      was no significant difference between groups. The retear rate on follow-up MRA
      was not significantly different between group A (8%) and B (11%). Patients in
      group B, compared with group A, showed a higher incidence of the preoperative
      impingement sign (89% vs 52%, respectively; P = .004), protruded spur on the
      acromion undersurface (69% vs 0%, respectively; P < .001), and concomitant
      acromioplasty (93% vs 24%, respectively; P < .001). CONCLUSION: Both articular
      and bursal side PTRCTs showed significant functional improvements after
      arthroscopic repair. The bursal side tears had a higher incidence of impingement
      sign at preoperative examination and more often had a protruded spur on the
      acromion undersurface.

PMID- 23880401
TI  - Intracellular and circulating neuronal antinuclear antibodies in human epilepsy.
AB  - There are overwhelming data supporting the inflammatory origin of some epilepsies
      (e.g., Rasmussen's encephalitis and limbic encephalitis). Inflammatory epilepsies
      with an autoimmune component are characterized by autoantibodies against membrane
      bound, intracellular or secreted proteins (e.g., voltage gated potassium
      channels). Comparably, little is known regarding autoantibodies targeting nuclear
      antigen. We tested the hypothesis that in addition to known epilepsy-related
      autoantigens, the human brain tissue and serum from patients with epilepsy
      contain autoantibodies recognizing nuclear targets. We also determined the
      specific nuclear proteins acting as autoantigen in patients with epilepsy. Brain
      tissue samples were obtained from patients undergoing brain resections to treat
      refractory seizures, from the brain with arteriovenous malformations or from post
      mortem multiple sclerosis brain. Patients with epilepsy had no known history of
      autoimmune disease and were not diagnosed with autoimmune epilepsy. Tissue was
      processed for immunohistochemical staining. We also obtained subcellular
      fractions to extract intracellular IgGs. After separating nuclear antibody
      antigen complexes, the purified autoantigen was analyzed by mass spectrometry.
      Western blots using autoantigen or total histones were probed to detect the
      presence of antinuclear antibodies in the serum of patients with epilepsy.
      Additionally, HEp-2 assays and antinuclear antibody ELISA were used to detect the
      staining pattern and specific presence of antinuclear antibodies in the serum of
      patients with epilepsy. Brain regions from patients with epilepsy characterized
      by blood-brain barrier disruption (visualized by extravasated albumin) contained
      extravasated IgGs. Intracellular antibodies were found in epilepsy (n=13/13) but
      not in multiple sclerosis brain (n=4/4). In the brain from patients with
      epilepsy, neurons displayed higher levels of nuclear IgGs compared to glia. IgG
      colocalized with extravasated albumin. All subcellular fractions from brain
      resections of patients with epilepsy contained extravasated IgGs (n=10/10), but
      epileptogenic cortex, where seizures originated from, displayed the highest
      levels of chromatin-bound IgGs. In the nuclear IgG pool, anti-histone
      autoantibodies were identified by two independent immunodetection methods. HEp-2
      assay and ELISA confirmed the presence of anti-histone (n=5/8) and anti-chromatin
      antibodies in the serum from patients with epilepsy. We developed a multi-step
      approach to unmask autoantigens in the brain and sera of patients with epilepsy.
      This approach revealed antigen-bound antinuclear antibodies in neurons and free
      antinuclear IgGs in the serum of patients with epilepsy. Conditions with blood
      brain barrier disruption but not seizures, were characterized by extravasated but
      not chromatin-bound IgGs. Our results show that the pool of intracellular IgG in
      the brain of patients with epilepsy consists of nucleus-specific autoantibodies
      targeting chromatin and histones. Seizures may be the trigger of neuronal uptake
      of antinuclear antibodies. 

PMID- 23880403
TI  - Accelerated weightbearing rehabilitation after matrix-induced autologous
      chondrocyte implantation in the tibiofemoral joint: early clinical and
      radiological outcomes.
AB  - BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) has become
      an established technique for the repair of full-thickness chondral defects in the
      knee, although best patient outcomes appear limited by a lack of evidence-based
      knowledge on how to progressively increase postoperative weightbearing (WB) and
      rehabilitation exercises. HYPOTHESIS: To determine the safety and efficacy of an
      accelerated WB regimen after MACI in the tibiofemoral joint. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: Clinical and
      radiological assessments were performed in 28 knees at 12 months after MACI to
      the medial or lateral femoral condyle. Both rehabilitation interventions sought
      to protect the implant for an initial period and then incrementally increase load
      bearing. Under the "accelerated" (AR) protocol, patients reached full WB at 6
      weeks after surgery compared with 8 weeks for what was considered to be the
      current "best practice" (CR) WB regimen based on previous research. Assessments
      included the Knee Injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short
      Form Health Survey (SF-36), visual analog scale, 6-minute walk test, and active
      knee range of motion (ROM). High-resolution magnetic resonance imaging (MRI) was
      used to describe the quality and quantity of repair tissue via the assessment of
      pertinent parameters of graft repair as well as an MRI composite score. RESULTS:
      Patients in both groups demonstrated significant improvement (P < .05) in all
      clinical measures over the preoperative and postoperative timeline from before
      surgery to 12 months after surgery. The AR group reported significantly better (P
      < .05) SF-36 physical component scores at 8 weeks and significantly greater (P <
      .05) KOOS quality of life scores at 6 and 12 months postoperatively. Although no
      differences (P > .05) were observed between the 2 groups for active knee ROM, the
      AR group did achieve full active knee extension as early as 4 weeks compared with
      the CR group at 12 weeks. There was no difference (P > .05) in graft quality as
      assessed by MRI (MOCART composite score: AR, 3.34; CR, 3.04), with no patients
      suffering any adverse effects from the implant up to 12 months, regardless of the
      rehabilitation protocol employed. CONCLUSION: The AR approach that reduced the
      length of time spent ambulating on crutches resulted in improved general physical
      function and quality of life and an earlier attainment of full active knee
      extension when compared with the CR approach. There were no graft complications
      ascertained through MRI. This regimen appears safe and may potentially speed up
      the recovery of normal gait function. A larger patient cohort and follow-up are
      required to observe long-term graft outcomes.

PMID- 23880404
TI  - Does high knee flexion cause separation of meniscal repairs?
AB  - BACKGROUND: Previous clinical studies comparing nonrestrictive and restrictive
      protocols after meniscal repair have shown no difference in outcomes; however,
      some surgeons still limit range of motion out of concern that it will place undue
      stress on the repair. HYPOTHESIS: Large acute medial meniscal tears will gap
      during simulated open chain exercises at high flexion angles, and a repaired
      construct with vertical mattress sutures will not gap. STUDY DESIGN: Controlled
      laboratory study. METHODS: Tantalum beads were implanted in the medial menisci of
      6 fresh-frozen cadaveric knees via an open posteromedial approach. Each knee
      underwent 10 simulated open chain flexion cycles with loading of the quadriceps
      and hamstrings. Testing was performed on 3 different states of the meniscus:
      intact, torn, and repaired. Biplanar radiographs were taken of the loaded knee in
      90 degrees , 110 degrees , and 135 degrees  of flexion for each state. A 2.5-cm
      tear was created in the posteromedial meniscus and repaired with inside-out
      vertical mattress sutures. Displacement of pairs of beads spanning the tear was
      measured in all planes by use of radiostereometric analysis (RSA) with an
      accuracy of better than 80 MUm. RESULTS: With a longitudinal tear, compression
      rather than gapping occurred in all 3 regions of the posterior horn of the
      meniscus (mean +/- standard deviation for medial collateral ligament [MCL], -321
      +/- 320 MUm; midposterior, -487 +/- 256 MUm; root, -318 +/- 150 MUm) with knee
      flexion. After repair, meniscal displacement returned part way to intact values
      in both the MCL (+55 +/- 250 MUm) and root region (-170 +/- 123 MUm) but not the
      midposterior region, where further compression was seen (-661 +/- 278 MUm).
      CONCLUSIONS: Acute posteromedial meniscal tears and repairs with vertical
      mattress sutures do not gap, but rather compress in the transverse plane at
      higher flexion angles when subjected to physiologic loads consistent with active,
      open kinetic chain range of motion rehabilitation exercises. The kinematics of
      the repaired meniscus more closely resemble that of the intact meniscus than that
      of the torn meniscus in regions adjacent to the MCL and the root but not in the
      midposterior region, where meniscal repair led to increased compression across
      the tear plane. CLINICAL RELEVANCE: This study supports the idea that
      nonrestrictive unresisted open chain range of motion protocols do not place undue
      stress on meniscal repairs.

PMID- 23880405
TI  - Methionine sulfoxide reductase A rs10903323 G/A polymorphism is associated with
      increased risk of coronary artery disease in a Chinese population.
AB  - OBJECTIVE: Coronary artery disease (CAD) is a complex disease resulting from a
      combination of environmental and genetic factors. We hypothesized that
      polymorphisms in methionine sulfoxide reductase A (MSRA: rs10903323 G/A) and
      vascular endothelial growth factor A (VEGFA: rs699947 C/A, rs2010963 G/C, and
      rs3025039 C/T) contribute to CAD susceptibility. DESIGNS AND METHODS: We examined
      the association between the four polymorphisms and the risk of CAD in a Chinese
      population of 435 CAD patients and 480 controls. Genotyping was performed using
      matrix-assisted laser desorption ionization/time-of-flight mass spectrometry
      (MALDI/TOF-MS). RESULTS: When the MSRA rs10903323 GG homozygous genotype was used
      as the reference group, the GA and GA/AA genotypes were associated with a
      significantly increased risk of CAD (GA vs GG: adjusted OR=1.36, 95% CI=1.02
      1.82, p=0.038; GA/AA vs GG: adjusted OR=1.33, 95% CI=1.01-1.76, p=0.042). The AA
      homozygous genotype was not associated with a risk of CAD. In the recessive
      model, when the MSRA rs10903323 GG/GA genotypes were used as the reference group,
      the AA homozygous genotype was not associated with a risk of CAD. Logistic
      regression analyses revealed that the VEGFA rs699947 C/A, VEGFA rs2010963 G/C,
      and VEGFA rs3025039 C/T polymorphisms were not associated with a risk of CAD.
      CONCLUSIONS: These findings suggest that the functional MSRA rs10903323 G/A
      polymorphism is associated with CAD development. However, our results allow only
      a preliminary conclusion, which must be validated with a larger study of a more
      diverse ethnic population.

PMID- 23880406
TI  - Raman spectroscopic investigation of the chemopreventive response of naringenin
      and its nanoparticles in DMBA-induced oral carcinogenesis.
AB  - Raman spectroscopy is a vibrational spectroscopic technique that can be used to
      optically probe the biomolecular changes associated with tumor progression. The
      aim of the present study is to investigate the biomolecular changes in
      chemopreventive response of prepared naringenin-loaded nanoparticles (NARNPs)
      relative to efficacy of free naringenin (NAR) during 7,12-dimethyl
      benz(a)anthracene (DMBA)-induced oral carcinogenesis by Fourier Transform Raman
      (FT-Raman) spectroscopy. Oral squamous cell carcinoma (OSCC) was developed in the
      buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid
      paraffin three times a week for 14weeks. Raman spectra differed significantly
      between the control and tumor tissues, with tumors showing higher percentage
      signals for nucleic acids, phenylalanine and tryptophan and a lower in the
      percentage of phospholipids. Moreover, oral administration of free NAR and NARNPs
      significantly increased phospholipids and decreased the levels of tryptophan,
      phenylalanine and nucleic acid contents. On a comparative basis, NARNPs was found
      to have a more potent antitumor effect than free NAR in completely preventing the
      formation of squamous cell carcinoma and in improving the biochemical status to a
      normal range in DMBA-induced oral carcinogenesis. The present study further
      suggest that Raman spectroscopy could be a valuable tool for rapid and sensitive
      detection of specific biomolecular changes in response to chemopreventive agents.

PMID- 23880407
TI  - Vibrational spectra, first order hyperpolarizability, NBO, Fukui function and
      HOMO-LUMO analysis of 2-[4-(1,3-benzodioxol-5-ylmethyl)-1-piperazinyl]
      pyrimidine.
AB  - In this work, the vibrational spectral analysis was carried out by using FT-Raman
      and FT-IR spectroscopy in the range 4000-100cm(-1) and 4000-400cm(-1)
      respectively, for 2-[4-(1, 3-benzodioxol-5-ylmethyl)-1-piperazinyl]
      pyrimidine(BDPP) molecule. Theoretical calculations were performed density
      functional theory (DFT) method using 6-31G(d,p) and 6-311G(d,p) basis sets. The
      assignments of vibrational spectra have been carried out with the help of normal
      co-ordinate analysis (NCA) following the scaled quantum mechanical force field
      (SQMFF) methodology. The results of the calculations were applied to simulated
      spectra of the title compound, which show excellent agreement with observed
      spectra. The frontier orbital energy gap and dipole moment illustrates the high
      reactivity of the title molecule. The first order hyperpolarizability (beta0) and
      related properties (MU, alpha and Deltaalpha) of the title molecule were also
      calculated. Stability of the molecule has been analyzed by natural bond orbital
      (NBO) analysis. Global reactivity and local reactivity descriptors of the title
      molecule have been calculated. Mulliken population analyses on atomic charges of
      the title compound have been calculated. Finally, molecular electrostatic
      potential (MEP) and HOMO-LUMO energy levels have been performed. 

PMID- 23880408
TI  - Spectroscopic investigation on the efficient organic nonlinear crystals of pure
      and diethanolamine added DAST.
AB  - 4-N,N'-dimethylamino-N-methyl-4-stilbazolium toyslate (DAST) and diethanolamine
      (DEA) added DAST crystals are grown by slow cooling method. The corresponding
      powder samples are examined by characterization studies such as XRD, FT-IR, FT
      Raman, UV-Vis-NIR and photoluminescence studies. From the powder X-ray
      diffraction, their lattice parameter values are found out. Since the vibrational
      spectra of the molecules are considerably contributed to their linear and
      nonlinear optical effects, Infrared and Raman spectroscopic studies are carried
      out for the samples. The UV-Vis-NIR absorption spectra of the samples are used to
      find the nature of transitions occurred in the samples. Using the density
      functional theory, highest occupied molecular orbital (HOMO) and lowest
      unoccupied molecular orbital (LUMO) analyses are done in order to explain the
      transition and density of states (DOS). The first order hyperpolarizability is
      calculated by HF and B3LYP/6-311 G(d,p) basis sets for the DAST molecule. From
      the photoluminescence (PL) spectral studies, the strong excitation emissions are
      observed. 

PMID- 23880409
TI  - Time-dependent density functional theory study of UV/vis spectra of natural
      styrylpyrones.
AB  - Natural styrylpyrones isolated from fungi are known for various biological
      activities including antioxidant activity by scavenging free radicals. UV/vis
      spectra play an important role in elucidating chemical structures of these
      compounds via identification of chromophore units. With the aim of predicting the
      UV/vis spectra of a series of natural styrylpyrones, we tested TD-DFT, CIS and
      ZINDO methods in gas and in PCM solvent. The results showed that the individual
      or combined B3P86 and B3LYP hybrid functionals are suitable to predict the
      maximum wavelength absorption bands (lambdamax) for styrylpyrones. The structure
      property relationship (SPR) study emphasized the role of (i) structural
      parameters (e.g., hydrogen bond and the length of conjugated double bonds) and
      (ii) electronic descriptors (e.g., ionization potential, electronic affinity,
      hardness and electrophilicity) in bathochromic and hypsochromic shifts of maximum
      wavelength absorption bands (lambdamax) of styrylpyrone derivatives. 

PMID- 23880410
TI  - Synthesis, spectroscopic and radical scavenging studies of palladium(II)
      hydrazide complexes.
AB  - In present study, a series of palladium(II) complexes with biologically active
      hydrazide ligands have been synthesized, characterized and screened for their
      antioxidant (superoxide and DPPH radical scavenging) properties. Spectral studies
      (FT-IR, EI-mass, (13)C and (1)H NMR spectroscopy) and physico-chemical
      measurements including elemental analysis, magnetic susceptibility and
      conductivity measurements represented square planar structure for all complexes.
      Substituted and unsubstituted benzohydrazides (1-4) have shown monodentate
      behavior forming complexes of general formula [PdL2Cl2]. However,
      pyridinecarbohydrazides (5 and 6) were coordinated in bidentate fashion of
      [PdLCl2] general formula producing stable five-membered chelate ring. All
      palladium complexes were found to be considerably more potent inhibitors of DPPH
      free radical compared to free hydrazides. These complexes are even stronger DPPH
      scavengers than standard antioxidant propyl gallate. The complexes have also
      shown good superoxide scavenging ability compared to inactive free hydrazides,
      however complexes are weaker superoxide scavengers than ascorbic acid, a standard
      superoxide inhibitor. An interesting structure activity relationship has been
      evaluated. 

PMID- 23880411
TI  - Two polyoxometalate-based coordination polymers constructed from Mn(II)-4,4'
      bipyridine-N,N'-dioxide building blocks and Keggin-type clusters: Syntheses,
      crystal structures and spectral properties.
AB  - Two polyoxometalate-based coordination polymers
      {[Mn2(dpdo)4(H2O)6](GeMo12O40)(H2O)4}n (1) and
      {[Mn2(dpdo)4(H2O)6](GeW12O40)(H2O)3}n (2) (dpdo=4,4'-bipyridine-N,N'-dioxide)
      have been synthesized and characterized by IR, elemental analysis, XRPD, TG
      technique and X-ray crystallography. The polymers 1 and 2 are basically
      isostructural and feature a 3D supramolecular framework decorated with Keggin
      type polyanion clusters based on one-dimension polymeric chains, which formed
      through the coordination interaction of Mn(II) and dpdo. The luminescent
      properties of the polymers were investigated in the solid state at room
      temperature. 

PMID- 23880412
TI  - Inorganic salts in atmospheric particulate matter: Raman spectroscopy as an
      analytical tool.
AB  - Atmospheric particulate matter is composed of inorganic and organic components of
      natural and anthropogenic origin. Wind-transport is probably the most important
      process responsible for the emission of solid particulate matter into the
      troposphere, but there are also important contributions from chemical reactions
      due to the interaction of different atmospheric components in presence of water
      and solar radiation. Sulfate, nitrate and carbonate salts can be both reactants
      and products in this complex dynamic system, and there is no doubt about their
      important impact on the climate. Both simple and mixed salts can be produced in
      atmosphere by dissolution-crystallization processes. The Raman spectra of 45
      representative salts of the atmospheric environment were recorded and the bands
      assigned. The chemometric analysis of the spectroscopic data of these 45 salts
      demonstrates the suitability of Raman spectroscopy to classify and identify
      sulfate, nitrate and carbonate salts of atmospheric importance. Salts were
      classified into three groups: "sulfates", "nitrates or carbonates" and "sulfate
      nitrates or sulfate-carbonate". This kind of information is relevant in
      atmospheric studies because specific characteristics of the salts can provide
      valuable information about the origin of the salts, the atmospheric chemistry and
      climate forcing, thus contributing to the evaluation of environmental impacts. 

PMID- 23880413
TI  - Pulmonary outcome and its correlates in school-aged children born with a
      gestational age <= 32 weeks.
AB  - BACKGROUND: There is limited data regarding factors influencing the respiratory
      outcome at school age of ex-preterms born since the introduction of antenatal
      steroids, surfactant replacement together with less aggressive ventilation.
      OBJECTIVES: To establish the main antenatal, neonatal and early childhood
      respiratory correlates of respiratory status in school-aged children born at <=
      32 weeks of gestation. METHODS: Ex-preterm children born at <= 32 weeks of
      gestation between 1997 and 2001 at Bordeaux University Hospital were evaluated at
      school age, using a respiratory questionnaire and lung function tests
      (spirometry, plethysmography, exercise challenge test and CO lung diffusing
      capacity DLCO measurements). Factors associated with lung function were
      investigated using polynomial regression analyses. RESULTS: Of the 151 included
      children [mean age: 8.6 +/- 0.8 years; mean gestational age, 30.1 +/- 1.7 weeks;
      mean birth weight = 1310 +/- 380 g; 68.2% ventilated at birth; 46.4% treated with
      surfactant; 36.4% with prior bronchopulmonary dysplasia (BPD)], 47% presented
      obstructive lung abnormalities, 11% restrictive or mixed lung abnormalities, 41%
      exercise-induced bronchoconstriction, and 15.5% reduced DLCO. Surfactant therapy
      was independently associated with a lower risk of lung abnormalities (p < 0.05).
      The association between BPD and lung abnormalities at school age was not
      significant, but prior BPD increased the risk of restrictive or mixed
      abnormalities (odds ratio: 6.11, confidence interval [1.1; 33.99]). Early
      childhood respiratory events were not associated with the occurrence of lung
      abnormalities. CONCLUSION: Children born at <= 32 weeks of gestation remain at
      risk for impaired lung function at school age in particular when they did not
      receive surfactant. Restrictive or mixed lung defects are mainly associated with
      prior BPD.

PMID- 23880414
TI  - Prediction of lethal pulmonary hypoplasia among high-risk fetuses via 2D and 3D
      ultrasonography.
AB  - OBJECTIVE: To compare accuracy between 3D and 2D ultrasonography for predicting
      lethal pulmonary hypoplasia (LPH) among high-risk fetuses. METHODS: In a cross
      sectional prospective study at a fetal medicine referral center in Brazil,
      bilateral fetal lung scans were evaluated for 54 fetuses with suspected LPH
      between May 2008 and June 2011. Measurements for predicting LPH were
      ultrasonographic fetal lung volume/estimated fetal weight ratio (US-FLW),
      observed/expected thoracic circumference (o/e-TC), observed/expected thoracic
      circumference/abdominal circumference (o/e-TC/AC), observed/expected thoracic
      area/heart area (o/e-TA/HA), observed/expected amniotic fluid index (o/e-AFI),
      and observed/expected total fetal lung volume (o/e-Tot-FLV). To evaluate accuracy
      in predicting LPH, receiver operating characteristic (ROC) curves were
      calculated, and areas under the curves (AUCs) were compared. The intraclass
      correlation coefficient (ICC) was used to assess 3D lung volume reproducibility.
      RESULTS: Data were compared for 47 newborns, of whom 34 had LPH (perinatal
      mortality 74.5%). The AUCs for predicting LPH were 0.93, 0.69, 0.55, 0.46, 0.71,
      and 0.86 for US-FLW, o/e-TC, o/e-TC/AC, o/e-TA/HA, o/e-AFI, and o/e-Tot-FLV,
      respectively. No significant intraobserver difference was observed in
      measurements of the right (ICC, 0.973; P < 0.0001) or left (ICC, 0.950; P <
      0.0001) lung volumes. CONCLUSION: Among high-risk fetuses, US-FLW by 2D/3D and
      o/e-Tot-FLV by 3D ultrasonography were more accurate than 2D parameters for
      predicting LPH.

PMID- 23880415
TI  - New insights on the genetic diversity of the honeybee parasite Nosema ceranae
      based on multilocus sequence analysis.
AB  - The microsporidian parasite Nosema ceranae is a common pathogen of the Western
      honeybee (Apis mellifera) whose variable virulence could be related to its
      genetic polymorphism and/or its polyphenism responding to environmental cues.
      Since the genotyping of N. ceranae based on unique marker sequences had been
      unsuccessful, we tested whether a multilocus approach, assessing the diversity of
      ten genetic markers - encoding nine proteins and the small ribosomal RNA subunit 
      allowed the discrimination between N. ceranae variants isolated from single A.
      mellifera individuals in four distant locations. High nucleotide diversity and
      allele content were observed for all genes. Most importantly, the diversity was
      mainly present within parasite populations isolated from single honeybee
      individuals. In contrast the absence of isolate differentiation precluded any
      taxa discrimination, even through a multilocus approach, but suggested that
      similar populations of parasites seem to infect honeybees in distant locations.
      As statistical evolutionary analyses showed that the allele frequency is under
      selective pressure, we discuss the origin and consequences of N. ceranae
      heterozygosity in a single host and lack of population divergence in the context
      of the parasite natural and evolutionary history.

PMID- 23880416
TI  - Pulsed-dose-rate brachytherapy for uterine cervix carcinoma: 10 years of
      experience with 226 patients at a single institution.
AB  - PURPOSE: To analyze the long-term results of pulsed-dose-rate (PDR) brachytherapy
      (BT) in cervical carcinoma patients treated at a single institution. METHODS AND
      MATERIALS: All patients with histopathologically proven Stages IB-IVA cervical
      carcinoma, treated at our institution with PDR intracavitary BT between April
      1996 and November 2007, were included in this retrospective analysis. All
      patients underwent primary pelvic radiotherapy (45 Gy) with concomitant
      chemotherapy from 1999 and PDR intracavitary BT (16 Gy to the clinical target
      volume), followed by hysterectomy in 124 patients. RESULTS: Two hundred twenty
      six patients received radiochemotherapy and BT. With a median followup of 81.7
      months, the 5-year overall survival, disease-free survival, and local control
      (LC) were 67%, 65%, and 80%, respectively; seventy-seven relapses were observed
      including 38 local recurrences. Multivariate analysis showed earlier FIGO
      (International Federation of Gynecology and Obstetrics) stage and absence of
      nodal involvement to be associated with better overall and disease-free
      survivals. Use of three-dimensional image-guided BT planning and absence of nodal
      involvement were associated with better LC in the multivariate analysis. Late
      Grade >=3 toxicity was experienced by 22 patients (9.7%), consisting of
      gastrointestinal toxicity for 6 patients, urinary tract for 10 patients,
      lymphatics for 3 patients, and vaginal toxicity for 3 patients. CONCLUSIONS: This
      study demonstrates excellent LC rates with few late side effects with PDR BT for
      cervix carcinoma, similar to those reported in the literature with historical
      standard low-dose-rate BT.

PMID- 23880417
TI  - The equivalent dose contribution from high-dose-rate brachytherapy to positive
      pelvic lymph nodes in locally advanced cervical cancer.
AB  - PURPOSE: Definitive radiation therapy for locally advanced cervical cancer
      involves external beam radiation therapy (EBRT) and high-dose-rate (HDR)
      brachytherapy. There remains controversy and practice pattern variation regarding
      the optimal radiation dose to metastatic pelvic lymph nodes (LNs). This study
      investigates the contribution of the pelvic LN dose from HDR brachytherapy.
      METHODS AND MATERIALS: For 17 patients with 36 positive pelvic LNs, each LN was
      contoured on a computed tomography (CT) plan for EBRT and on brachytherapy
      planning CTs using positron emission tomographic images obtained before
      chemoradiation. The mean delivered dose from each plan was recorded, and an
      equivalent dose in 2-Gy fractions (EQD2) was calculated. A Student's t test was
      performed to determine if the mean delivered dose is significantly different from
      the mean prescribed dose and EQD2. RESULTS: The average prescribed dose from the
      total EBRT was 54.09 Gy. The average prescribed HDR dose to International
      Commission on Radiation Units point A was 26.81 Gy. The average doses delivered
      to the involved LNs from EBRT and brachytherapy were 54.25 and 4.31 Gy,
      respectively, with the corresponding EQD2 of 53.45 and 4.00 Gy. There was no
      statistically significant difference (p < 0.05) between the mean delivered and
      the prescribed doses for EBRT and between the delivered dose and the EQD2 for
      EBRT and brachytherapy. CONCLUSIONS: Our study shows that the HDR contribution is
      7% (4.00 Gy) of the total EQD2 (57.45 Gy). The HDR contribution should be
      accounted for when prescribing the EBRT boost dose to pelvic LNs for the optimal
      therapeutic dose.

PMID- 23880418
TI  - One-dimensional TRFLP-SSCP is an effective DNA fingerprinting strategy for soil
      Archaea that is able to simultaneously differentiate broad taxonomic clades based
      on terminal fragment length polymorphisms and closely related sequences based on
      single stranded conformation polymorphisms.
AB  - DNA fingerprinting methods provide a means to rapidly compare microbial
      assemblages from environmental samples without the need to first cultivate
      species in the laboratory. The profiles generated by these techniques are able to
      identify statistically significant temporal and spatial patterns, correlations to
      environmental gradients, and biological variability to estimate the number of
      replicates for clone libraries or next generation sequencing (NGS) surveys. Here
      we describe an improved DNA fingerprinting technique that combines terminal
      restriction fragment length polymorphisms (TRFLP) and single stranded
      conformation polymorphisms (SSCP) so that both can be used to profile a sample
      simultaneously rather than requiring two sequential steps as in traditional two
      dimensional (2-D) gel electrophoresis. For the purpose of profiling Archaeal 16S
      rRNA genes from soil, the dynamic range of this combined 1-D TRFLP-SSCP approach
      was superior to TRFLP and SSCP. 1-D TRFLP-SSCP was able to distinguish broad
      taxonomic clades with genetic distances greater than 10%, such as Euryarchaeota
      and the Thaumarchaeal clades g_Ca. Nitrososphaera (formerly 1.1b) and o_NRP-J
      (formerly 1.1c) better than SSCP. In addition, 1-D TRFLP-SSCP was able to
      simultaneously distinguish closely related clades within a genus such as
      s_SCA1145 and s_SCA1170 better than TRFLP. We also tested the utility of 1-D
      TRFLP-SSCP fingerprinting of environmental assemblages by comparing this method
      to the generation of a 16S rRNA clone library of soil Archaea from a restored
      Tallgrass prairie. This study shows 1-D TRFLP-SSCP fingerprinting provides a
      rapid and phylogenetically informative screen of Archaeal 16S rRNA genes in soil
      samples. 

PMID- 23880419
TI  - Biochemical changes in the liver and gill of Cathorops spixii collected
      seasonally in two Brazilian estuaries under varying influences of anthropogenic
      activities.
AB  - In order to understand environmental health by the use of a bioindicator species
      in estuaries, biochemical responses observed in the catfish Cathorops spixii such
      as catalase (CAT), glutathione-S-transferase (GST), lipid peroxidation (LPO) and
      acetylcholinesterase (AChE) were evaluated in liver and muscle. Furthermore,
      histological changes were also verified in liver and gills preparations. Fish
      were collected in three sites of the Santos-Sao Vicente estuary located at Sao
      Paulo (Brazil), subjected to varying levels of inputs of pollutants. For a
      reference site, specimens were sampled at Cananeia estuary at southern coast of
      Sao Paulo, a region with low anthropogenic influence. In general, no significant
      seasonal differences in antioxidant enzymes and lipid peroxidation responses were
      found in the organisms from the Cananeia estuary. However, in the polluted
      estuary (Santos-Sao Vicente), biochemical responses were observed by increases in
      GST hydroperoxides and decreases in AChE activities in the summer. Inhibition of
      AChE expression in fish from different areas of the Santos-Sao Vicente estuary in
      the summer was also found and can indicate neurotoxic effects in these organisms.
      Histopathological observation of gill and liver showed severe lesions, such as
      lamellar fusion and necrosis. 

PMID- 23880420
TI  - Regional gaps in the provision of inpatient rehabilitation services for the
      elderly in Israel: Results of a national survey.
AB  - BACKGROUND: Medical events, such as stroke, limb fractures, joint replacements
      and spinal injuries, can lead to acute functional disability at all ages and to
      chronic disability, especially among the elderly. Rehabilitation is, therefore,
      essential for the prevention of permanent disability among older individuals.
      There are international practice guidelines for stroke and hip fracture
      management, including recommendations that rehabilitation services be an integral
      part of the provision of treatment in either an inpatient setting or in the
      community. There are no organized data on provision of rehabilitation services in
      Israel or on the distribution of these services throughout the country. Such
      information would be of great assistance in designing these services where they
      are needed and in making changes in the existing ones where necessary. METHODS:
      Patients aged 65 years or older with stroke or hip fracture were identified
      through one-day surveys conducted in 2009-2010 in all 26 acute care hospitals in
      Israel. Data on inpatient and ambulatory rehabilitation services were collected
      from discharge medical summaries, telephone interviews with the patients or their
      relatives and reports from the healthcare provider. The extent of rehabilitation
      services was described and the association between receipt of inpatient
      rehabilitation and the geographic district based on the patients' listed address
      was examined in a multivariate analysis. RESULTS: A total of 570 patients with
      stroke and 768 patients with hip fracture were identified and interviews were
      conducted in regards to 421 and 672 respectively. Out of the stroke patients
      238(56.5%) received inpatient rehabilitation, 46(10.9%) received ambulatory
      rehabilitation treatment without inpatient phase and 137 (32.5%) received no
      rehabilitation. In fracture these rates were 494(73.5%), 96(14.3%) and 82(12.2%)
      respectively. Patients living in districts with lower availability of
      rehabilitation beds were less likely to receive inpatient rehabilitation after
      controlling for patient characteristics. CONCLUSIONS: Regional disparities in the
      provision of inpatient rehabilitation care for elderly after an acute episode of
      stroke or hip fracture were identified and could be partially attributed to the
      distribution of rehabilitation beds. These findings highlight the need to plan
      the rehabilitation resources based on the population needs and to routinely
      monitor the provision of these services.

PMID- 23880422
TI  - Response to 're. internal iliac artery coverage during endovascular aneurysm
      repair'.

PMID- 23880421
TI  - Predicted risks of radiogenic cardiac toxicity in two pediatric patients
      undergoing photon or proton radiotherapy.
AB  - BACKGROUND: Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies
      found in children and young adults, and radiotherapy is part of the standard
      treatment. It was reported that these patients who received radiation therapy
      have an increased risk of cardiovascular late effects. We compared the predicted
      risk of developing radiogenic cardiac toxicity after photon versus proton
      radiotherapies for a pediatric patient with HD and a pediatric patient with MB.
      METHODS: In the treatment plans, each patient's heart was contoured in fine
      detail, including substructures of the pericardium and myocardium. Risk
      calculations took into account both therapeutic and stray radiation doses. We
      calculated the relative risk (RR) of cardiac toxicity using a linear risk model
      and the normal tissue complication probability (NTCP) values using relative
      seriality and Lyman models. Uncertainty analyses were also performed. RESULTS:
      The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37
      (photon), respectively; the RR values for the MB patient were 1.28 (proton) and
      8.39 (photon), respectively. The predicted NTCP values for the HD patient were
      2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and
      1.92% (photon) for the whole heart. The predicted ratios of NTCP values
      (proton/photon) for the MB patient were much less than unity. Uncertainty
      analyses revealed that the predicted ratio of risk between proton and photon
      therapies was sensitive to uncertainties in the NTCP model parameters and the
      mean radiation weighting factor for neutrons, but was not sensitive to heart
      structure contours. The qualitative findings of the study were not sensitive to
      uncertainties in these factors. CONCLUSIONS: We conclude that proton and photon
      radiotherapies confer similar predicted risks of cardiac toxicity for the HD
      patient in this study, and that proton therapy reduced the predicted risk for the
      MB patient in this study.

PMID- 23880423
TI  - Hemodynamic assessment of celiaco-mesenteric anastomosis in patients with
      pancreaticoduodenal artery aneurysm concomitant with celiac artery occlusion
      using flow-sensitive four-dimensional magnetic resonance imaging.
AB  - OBJECTIVES: Many pancreaticoduodenal artery (PDA) aneurysms are associated with
      celiac artery (CA) stenosis. The pathogenesis of PDA aneurysm may be associated
      with hemodynamic changes due to CA stenosis/occlusion. The aim of this study was
      to assess the hemodynamic changes of celiaco-mesenteric anastomosis in patients
      with PDA aneurysms concomitant with CA occlusion using four-dimensional flow
      sensitive magnetic resonance imaging (4D-Flow). METHODS: 4D-Flow was performed
      preoperatively on five patients. Seven age- and sex-matched individuals were used
      as controls. Hemodynamic parameters such as flow volume and maximum flow velocity
      in PDAs, gastroduodenal arteries, common hepatic arteries, and superior
      mesenteric arteries were compared between both groups. Wall shear stress (WSS)
      and oscillatory shear index (OSI) were mapped in both groups. RESULTS: In the
      patient group, 4D-Flow identified retrograde flow of both gastroduodenal arteries
      and common hepatic arteries. Heterogeneous distribution patterns of both WSS and
      OSI were identified across the entire PDA in the patient group. OSI mapping
      showed multiple regions with extremely high OSI values (OSI > 0.3) in all
      patients. All PDA aneurysms, which were surgically resected, were
      atherosclerotic. CONCLUSIONS: 4D-Flow identified hemodynamic changes in celiaco
      mesenteric arteries in patients with PDA aneurysms with concomitant CA occlusion.
      These hemodynamic changes may be associated with PDA aneurysm formation.

PMID- 23880424
TI  - Occupational radiation exposure and the vascular interventionalist.

PMID- 23880425
TI  - Charge regulation in biomolecular solution.
AB  - Proteins and other biomolecules contain acidic and basic titratable groups that
      give rise to intricate charge distributions and control electrostatic
      interactions. 'Charge regulation' concerns how the proton equilibria of these
      sites are perturbed when approached by alien molecular matter such as other
      proteins, surfaces and membranes, DNA, polyelectrolytes etc. Importantly, this
      perturbation generates a charge response that leads to attractive intermolecular
      interactions that can be conveniently described by a single molecular property -
      the charge capacitance. The capacitance quantifies molecular charge fluctuations,
      i.e. it is the variance of the mean charge and is an intrinsic property on par
      with the net charge and the dipole moment. It directly enters the free energy
      expression for intermolecular interactions and can be obtained experimentally
      from the derivative of the titration curve or theoretically from simulations. In
      this review, we focus on the capacitance concept as a predictive parameter for
      charge regulation and demonstrate how it can be used to estimate the interaction
      of a protein with other proteins, polyelectrolytes, membranes as well as with
      ligands.

PMID- 23880426
TI  - The influence of different contrast medium concentrations and injection protocols
      on quantitative and clinical assessment of FDG-PET/CT in lung cancer.
AB  - OBJECTIVES: To compare the effects of two different contrast medium
      concentrations for use in computed X-ray tomography (CT) employing two different
      injection protocols on positron emission tomography (PET) reconstruction in
      combined 2-(18)F-desoxyglucose (FDG) PET/CT in patients with a suspicion of lung
      cancer. METHODS: 120 patients with a suspicion of lung cancer were enrolled
      prospectively. PET images were reconstructed with the non-enhanced and venous
      phase contrast CT obtained after injection of iopromide 300 mg/ml or 370 mg/ml
      using either a fixed-dose or a body surface area adapted injection protocol.
      Maximum and mean standardized uptake values (SUV(max) and SUV(mean)) and contrast
      enhancement (HU) were determined in the subclavian vein, ascending aorta,
      abdominal aorta, inferior vena cava, portal vein, liver and kidney and in the
      suspicious lung lesion. PET data were evaluated visually for the presence of
      malignancy and image quality. RESULTS: At none of the sites a significant
      difference in the extent of the contrast enhancement between the four different
      protocols was found. However, the variability of the contrast enhancement at
      several anatomical sites was significantly greater in the fixed dose groups than
      in the BSA groups for both contrast medium concentrations. At none of the sites a
      significant difference was found in the extent of the SUV(max) and SUV(mean)
      increase as a result of the use of the venous phase contrast enhanced CT for
      attenuation. Visual clinical evaluation of lesions showed no differences between
      contrast and non-contrast PET/CT (P=0.32). CONCLUSIONS: Contrast enhanced CT for
      attenuation correction in combined PET/CT in lung cancer affects neither the
      clinical assessment nor image quality of the PET-images. A body surface adapted
      contrast medium protocol reduces the interpatient variability in contrast
      enhancement.

PMID- 23880427
TI  - Microcantilever based disposable viscosity sensor for serum and blood plasma
      measurements.
AB  - This paper proposes a novel method for measuring blood plasma and serum viscosity
      with a microcantilever-based MEMS sensor. MEMS cantilevers are made of
      electroplated nickel and actuated remotely with magnetic field using an electro
      coil. Real-time monitoring of cantilever resonant frequency is performed remotely
      using diffraction gratings fabricated at the tip of the dynamic cantilevers. Only
      few nanometer cantilever deflection is sufficient due to interferometric
      sensitivity of the readout. The resonant frequency of the cantilever is tracked
      with a phase lock loop (PLL) control circuit. The viscosities of liquid samples
      are obtained through the measurement of the cantilever's frequency change with
      respect to a reference measurement taken within a liquid of known viscosity. We
      performed measurements with glycerol solutions at different temperatures and
      validated the repeatability of the system by comparing with a reference
      commercial viscometer. Experimental results are compared with the theoretical
      predictions based on Sader's theory and agreed reasonably well. Afterwards
      viscosities of different Fetal Bovine Serum and Bovine Serum Albumin mixtures are
      measured both at 23 degrees C and 37 degrees C, body temperature. Finally the
      viscosities of human blood plasma samples taken from healthy donors are measured.
      The proposed method is capable of measuring viscosities from 0.86 cP to 3.02 cP,
      which covers human blood plasma viscosity range, with a resolution better than
      0.04 cP. The sample volume requirement is less than 150 MUl and can be reduced
      significantly with optimized cartridge design. Both the actuation and sensing are
      carried out remotely, which allows for disposable sensor cartridges.

PMID- 23880428
TI  - The effect of the Medicare Part D benzodiazepine exclusion on the utilization
      patterns of benzodiazepines and substitute medications.
AB  - BACKGROUND: Although the benzodiazepine exclusion policy in the U.S. Medicare
      Part D drug coverage program has been studied, little information is available on
      individual use and switching patterns between benzodiazepines and substitute
      medications. Patients voluntarily were continuing or stopping benzodiazepines or
      switching to substitute medications. These individual-level outcomes can provide
      information beneficial to providers and policymakers to better understand the
      intended and unintended consequences of exclusion policies. OBJECTIVE: The
      objective was to determine the effect of the Medicare Part D benzodiazepine
      exclusion on the utilization patterns of benzodiazepines and substitute
      medications by a select group of Medicare beneficiaries for a year following
      implementation of the exclusion. This research focused on the examination of the
      within-person patterns of benzodiazepine use and factors associated with these
      patterns. METHODS: A quasi-experimental, comparative study was used to analyze
      prescription patterns and multinomial regression models were applied to
      investigate factors predicting different benzodiazepine use patterns. Pharmacy
      dispensing data for continuously eligible Medicare beneficiaries with at least
      one benzodiazepine fill in 2005 were reduced to a comparison group of 216
      individuals with continual coverage and an intervention group of 250 individuals
      who lost coverage for benzodiazepines. Four individual patients' drug use
      patterns, continuation, switch, fluid movement, and cessation were identified by
      sorting and arraying pharmacy dispensing data to apply systematic drug file
      review. Multinomial regression models were used to examine the impact of
      coverage, demographic, medical, economic, and pharmaceutical factors. RESULTS:
      Significantly more Medicare seniors who lost benzodiazepine coverage switched to
      potential substitute medications than those who continued to have coverage.
      Interestingly, 12 percent of affected seniors and 6 percent of unaffected seniors
      switched from and back to benzodiazepines (fluid movement). Zolpidem was the most
      popular substitute agent despite being an expensive brand-name drug. Regression
      models revealed that affected individuals had nearly two times the odds of
      engaging in switch-related patterns than those who had continuous coverage. Also,
      women were twice as likely to discontinue benzodiazepines as men. CONCLUSIONS:
      More seniors who lost benzodiazepine coverage engaged in medication switching,
      and women were more likely to stop benzodiazepines after the implementation of
      the exclusion policy.

PMID- 23880430
TI  - Deciphering the onychophoran 'segmentation gene cascade': Gene expression reveals
      limited involvement of pair rule gene orthologs in segmentation, but a highly
      conserved segment polarity gene network.
AB  - The hallmark of the arthropods is their segmented body, although origin of
      segmentation, however, is unresolved. In order to shed light on the origin of
      segmentation we investigated orthologs of pair rule genes (PRGs) and segment
      polarity genes (SPGs) in a member of the closest related sister-group to the
      arthropods, the onychophorans. Our gene expression data analysis suggests that
      most of the onychophoran PRGs do not play a role in segmentation. One possible
      exception is the even-skipped (eve) gene that is expressed in the posterior end
      of the onychophoran where new segments are likely patterned, and is also
      expressed in segmentation-gene typical transverse stripes in at least a number of
      newly formed segments. Other onychophoran PRGs such as runt (run), hairy/Hes
      (h/Hes) and odd-skipped (odd) do not appear to have a function in segmentation at
      all. Onychophoran PRGs that act low in the segmentation gene cascade in insects,
      however, are potentially involved in segment-patterning. Most obvious is that
      from the expression of the pairberry (pby) gene ortholog that is expressed in a
      typical SPG-pattern. Since this result suggested possible conservation of the SPG
      network we further investigated SPGs (and associated factors) such as Notum in
      the onychophoran. We find that the expression patterns of SPGs in arthropods and
      the onychophoran are highly conserved, suggesting a conserved SPG-network in
      these two clades, and indeed also in an annelid. This may suggest that the common
      ancestor of lophotrochozoans and ecdysozoans was already segmented utilising the
      same SPG-network, or that the SPG-network was recruited independently in annelids
      and onychophorans/arthropods.

PMID- 23880429
TI  - Postembryonic lineages of the Drosophila brain: I. Development of the lineage
      associated fiber tracts.
AB  - Neurons of the Drosophila central brain fall into approximately 100 paired
      groups, termed lineages. Each lineage is derived from a single asymmetrically
      dividing neuroblast. Embryonic neuroblasts produce 1,500 primary neurons (per
      hemisphere) that make up the larval CNS followed by a second mitotic period in
      the larva that generates approximately 10,000 secondary, adult-specific neurons.
      Clonal analyses based on previous works using lineage-specific Gal4 drivers have
      established that such lineages form highly invariant morphological units. All
      neurons of a lineage project as one or a few axon tracts (secondary axon tracts,
      SATs) with characteristic trajectories, thereby representing unique hallmarks. In
      the neuropil, SATs assemble into larger fiber bundles (fascicles) which
      interconnect different neuropil compartments. We have analyzed the SATs and
      fascicles formed by lineages during larval, pupal, and adult stages using
      antibodies against membrane molecules (Neurotactin/Neuroglian) and synaptic
      proteins (Bruchpilot/N-Cadherin). The use of these markers allows one to identify
      fiber bundles of the adult brain and associate them with SATs and fascicles of
      the larval brain. This work lays the foundation for assigning the lineage
      identity of GFP-labeled MARCM clones on the basis of their close association with
      specific SATs and neuropil fascicles, as described in the accompanying paper
      (Wong et al., 2013. Postembryonic lineages of the Drosophila brain: II.
      Identification of lineage projection patterns based on MARCM clones. Submitted.).

PMID- 23880432
TI  - Estimating the potential water reuse based on fuzzy reasoning.
AB  - Studies worldwide suggest that the risk of water shortage in regions affected by
      climate change is growing. Decision support tools can help governments to
      identify future water supply problems in order to plan mitigation measures.
      Treated wastewater is considered a suitable alternative water resource and it is
      used for non-potable applications in many dry regions around the world. This work
      describes a decision support system (DSS) that was developed to identify current
      water reuse potential and the variables that determine the reclamation level. The
      DSS uses fuzzy inference system (FIS) as a tool and multi-criteria decision
      making is the conceptual approach behind the DSS. It was observed that water
      reuse level seems to be related to environmental factors such as drought, water
      exploitation index, water use, population density and the wastewater treatment
      rate, among others. A dataset was built to analyze these features through water
      reuse potential with a FIS that considered 155 regions and 183 cities. Despite
      some inexact fit between the classification and simulation data for agricultural
      and urban water reuse potential it was found that the FIS was suitable to
      identify the water reuse trend. Information on the water reuse potential is
      important because it issues a warning about future water supply needs based on
      climate change scenarios, which helps to support decision making with a view to
      tackling water shortage. 

PMID- 23880431
TI  - Performance of an aerobic granular sequencing batch reactor fed with wastewaters
      contaminated with Zn2+.
AB  - The main aim of this study was to investigate the performance of an aerobic
      granular sludge sequencing batch reactor (AGS-SBR) receiving water streams
      supplied with different loads of Zn(2+) (50 and 100 mg L(-1)) during an operation
      of 866 cycles (ca. 109 days). When the metal was not fed, chemical oxygen demand
      (COD), PO4(3-) and NH4(+) were efficiently removed, with efficiencies of 56, 23
      and 72% respectively. DGGE profiles showed that Zn(2+) supply negatively affected
      the bacterial diversity and community structure of the granules. Consequently,
      the shock loadings with Zn(2+), particularly at the higher levels (100 mg L(-1)),
      affected the nutrient removal in the AGS-SBR, although the reactor still
      generally complied with admissible legal values concerning organic matter,
      nitrogen and Zn. Simultaneous removal of PO4(3-) and TSS in such conditions needs
      further refining but the application of aerobic granular SBR in the treatment of
      Zn(2+) contaminated wastewaters seems viable. 

PMID- 23880433
TI  - A review of nitrous oxide mitigation by farm nitrogen management in temperate
      grassland-based agriculture.
AB  - Nitrous oxide (N2O) emission from grassland-based agriculture is an important
      source of atmospheric N2O. It is hence crucial to explore various solutions
      including farm nitrogen (N) management to mitigate N2O emissions without
      sacrificing farm profitability and food supply. This paper reviews major N
      management practices to lower N2O emission from grassland-based agriculture.
      Restricted grazing by reducing grazing time is an effective way to decrease N2O
      emissions from excreta patches. Balancing the protein-to-energy ratios in the
      diets of ruminants can also decrease N2O emissions from excreta patches. Among
      the managements of synthetic fertilizer N application, only adjusting fertilizer
      N rate and slow-released fertilizers are proven to be effective in lowering N2O
      emissions. Use of bedding materials may increase N2O emissions from animal
      houses. Manure storage as slurry, manipulating slurry pH to values lower than 6
      and storage as solid manure under anaerobic conditions help to reduce N2O
      emissions during manure storage stage. For manure land application, N2O emissions
      can be mitigated by reducing manure N inputs to levels that satisfy grass needs.
      Use of nitrification inhibitors can substantially lower N2O emissions associated
      with applications of fertilizers and manures and from urine patches. N2O
      emissions from legume based grasslands are generally lower than fertilizer-based
      systems. In conclusion, effective measures should be taken at each step during N
      flow or combined options should be used in order to mitigate N2O emission at the
      farm level. 

PMID- 23880434
TI  - Recently identified novel human astroviruses in children with diarrhea, China.

PMID- 23880435
TI  - Gradient sensing during chemotaxis.
AB  - Eukaryotic cells have the ability to sense chemoattractant gradients and to
      migrate toward the sources of attractants. The chemical gradient-guided cell
      movement is referred to as chemotaxis. Chemoattractants are detected by members
      of G-protein-coupled receptors (GPCRs) that link to heterotrimeric G-proteins.
      The GPCR/G-protein sensing machinery is able to translate external
      chemoattractants fields into intercellular cues, which direct reorganization of
      the actin cytoskeleton that drives cell movement. Here, I review our current
      understanding of the formation of chemoattractant gradients in vivo, the GPCR
      mediated gradient sensing, and the sophisticated signaling network that guides
      the function of the actin cytoskeleton. 

PMID- 23880436
TI  - Morphological transition in kleptochloroplasts after ingestion in the
      dinoflagellates Amphidinium poecilochroum and Gymnodinium aeruginosum
      (Dinophyceae).
AB  - The unarmoured marine dinoflagellate Amphidinium poecilochroum and the unarmoured
      freshwater dinoflagellate Gymnodinium aeruginosum both belonging to the same
      clade, are known to possess cryptomonad-derived kleptochloroplasts. Previous
      studies revealed that G. aeruginosum can synchronise the division of the
      chloroplast with its own cell division while no simultaneous division takes place
      in A. poecilochroum, which is interpreted to mean that state of
      kleptochloroplastidy in G. aeruginosum is closer to that of the initial
      acquisition of the 'true chloroplast' within the lineage. Although the general
      ultrastructure of these two species has been reported, the changes in the
      kleptochloroplast with time have never been followed. We observed morphological
      changes in kleptochloroplasts of A. poecilochroum and G. aeruginosum following
      the ingestion of cryptomonad cells, using light and transmission electron
      microscopes. In A. poecilochroum, the cryptomonad ejectosomes, mitochondria and
      cytoplasm were all actively transferred into digestive vacuoles within 1h of
      ingestion. The chloroplasts were deformed and the cryptomonad nucleus was
      digested after 3h. By contrast, in G. aeruginosum, the cryptomonad cytoplasm and
      nucleus were retained for 24h following ingestion, and the chloroplast was
      substantially enlarged. These differences imply that the retention of the
      cryptomonad nucleus is important for the maintenance of the chloroplast. 

PMID- 23880437
TI  - Research and data systems to promote equal access to postacute rehabilitation.
AB  - The first national study in Israel of post-acute rehabilitation service use for
      elderly patients with stroke and hip fracture reported regional variation in care
      receipt. Although lower likelihood of admission to inpatient rehabilitation was
      observed in districts with known shortages of rehabilitation beds, supply alone
      did not explain the findings. This commentary explores other potential
      contributing factors. It argues that greater uniformity in the process and
      documentation of discharge planning in combination with decision support would
      help to standardize provider behavior. Implementation of a system of functional
      status data collection that is linked to administrative data is recommended to
      enable examination of the impact of care receipt and variation. Additional
      research is needed to provide a clearer understanding of factors contributing to
      regional variation and to identify solutions to ensure equal access to post-acute
      rehabilitation services in Israel. 

PMID- 23880438
TI  - Linear center-of-mass dynamics emerge from non-linear leg-spring properties in
      human hopping.
AB  - Given the almost linear relationship between ground-reaction force and leg
      length, bouncy gaits are commonly described using spring-mass models with
      constant leg-spring parameters. In biological systems, however, spring-like
      properties of limbs may change over time. Therefore, it was investigated how much
      variation of leg-spring parameters is present during vertical human hopping. In
      order to do so, rest-length and stiffness profiles were estimated from ground
      reaction forces and center-of-mass dynamics measured in human hopping. Trials
      included five hopping frequencies ranging from 1.2 to 3.6 Hz. Results show that,
      even though stiffness and rest length vary during stance, for most frequencies
      the center-of-mass dynamics still resemble those of a linear spring-mass hopper.
      Rest-length and stiffness profiles differ for slow and fast hopping. Furthermore,
      at 1.2 Hz two distinct control schemes were observed.

PMID- 23880439
TI  - Geometric mouse variation: implications to the axial ulnar loading protocol and
      animal specific calibration.
AB  - Large variations in axial ulnar load strain calibration results suggest that
      animal-specific calibrations may be necessary. However, the optimal set of
      geometric measures for performing an animal-specific calibration are not known,
      potentially as a result of confounding effects associated with experimentally
      introduced variation. The purpose of this study was to characterize the inherent
      variability of ulnar geometric measures known to influence periosteal midshaft
      strain during axial ulnar exogenous loading, and to further quantify the
      relationship between the variance of those geometric measures and periosteal
      strain during axial loading. Thirty-nine right mouse forelimbs were scanned with
      microCT. Seven geometric measures that influence periosteal strain resulting from
      a combined axial and bending loading were computed and used to estimate animal
      specific strains on the periosteal midshaft. Animal specific strains were
      estimated using a theoretical model based on the generalized flexure formula. The
      predicted mean and standard deviation of the simulated midshaft strain gauge
      measurement resulting from the inter-animal geometric differences was -985 +/-
      148 MUepsilon/N. The complete beam bending term associated with bending about the
      I(min) axis accounted for 89% of the variance and reduced the residual RMSE to
      50.4 MUepsilon. Eccentricity associated with the axial loading contributed a
      substantial portion of variation to the computed strain suggesting that
      calibration procedures to account for animal differences should incorporate that
      variable. The method developed in this study provides a relatively simple
      procedure for computing animal-specific strains using microCT scan data, without
      the need of a load/strain calibration study or computationally intensive finite
      element models.

PMID- 23880440
TI  - [Coordination in case management practices in the context of integrated home care
      networks devoted to the frail elderly, a qualitative exploratory analysis].
AB  - The objective of this article is to understand coordination as it unfolds in case
      management practices in the context of integrated care networks devoted to frail
      elderly individuals. More specifically, we describe practical coordination
      processes. We conducted a qualitative exploratory study using an embedded case
      study design. Our study covers three health and social service centers in Quebec.
      We noted that coordination produces convention in case management practices
      through a process of bringing together different types of compromise in home care
      situations where multidimensionality appears to be more or less important. We
      constructed four different types of compromise-producing convention with regard
      to coordination in case management practices: compromise at the interface,
      scheduling compromise, compromise of opportunity, and compromising change.

PMID- 23880441
TI  - Metagenome analyses reveal the influence of the inoculant Lactobacillus buchneri
      CD034 on the microbial community involved in grass ensiling.
AB  - Silage is green fodder conserved by lactic acid fermentation performed by
      epiphytic lactic acid bacteria under anaerobic conditions. To improve the
      ensiling process and the quality of the resulting silage, starter cultures are
      added to the fresh forage. A detailed analysis of the microbial community playing
      a role in grass ensiling has been carried out by high throughput sequencing
      technologies. Moreover, the influence of the inoculant Lactobacillus buchneri
      CD034 on the microbial community composition was studied. For this purpose, grass
      was ensiled untreated or inoculated with L. buchneri CD034. The fresh forage as
      well as silages after 14 and 58 days of fermentation were characterized physico
      chemically. Characteristic silage conditions such as increased titers of lactic
      acid bacteria and higher concentrations of acetic acid were observed in the
      inoculated silage in comparison to the untreated samples. Taxonomic community
      profiles deduced from 16S rDNA amplicon sequences indicated that the relative
      abundance of Lactococci diminished in the course of fermentations and that the
      proportion of bacteria belonging to the phyla Proteobacteria and Bacteroidetes
      increased during the fermentation of untreated silage. In the inoculated silage,
      members of these phyla were repressed due to an increased abundance of
      Lactobacilli. In addition, metagenome analyses of silage samples confirmed
      taxonomic profiles based on 16S rDNA amplicons. Moreover, Lactobacillus
      plantarum, Lactobacillus brevis and Lactococcus lactis were found to be dominant
      species within silages as analyzed by means of fragment recruitments of
      metagenomic sequence reads on complete reference genome sequences. Fragment
      recruitments also provided clear evidence for the competitiveness of the
      inoculant strain L. buchneri CD034 during the fermentation of the inoculated
      silage. The inoculation strain was able to outcompete other community members and
      also affected physico-chemical characteristics of the silage. 

PMID- 23880442
TI  - Pushing the equilibrium of regio-complementary carboxylation of phenols and
      hydroxystyrene derivatives.
AB  - The enzymatic carboxylation of electron-rich aromatics, which represents a
      promising 'green' equivalent to the chemical Kolbe-Schmitt reaction, is
      thermodynamically disfavored and is therefore impeded by incomplete conversions.
      Optimization of the reaction conditions, such as pH, temperature, substrate
      concentration and the use of organic co-solvents and/or ionic liquids allowed to
      push the conversion in favor of carboxylation by a factor of up to 50%. Careful
      selection of the type of bicarbonate salt used as CO2 source was crucial to
      ensure optimal activities. Among two types of carboxylases tested with their
      natural substrates, benzoic acid decarboxylase from Rhizobium sp. proved to be
      significantly more stable than phenolic acid decarboxylase from Mycobacterium
      colombiense; it tolerated reaction temperatures of up to 50  degrees C and
      substrate concentrations of up to 100mM and allowed efficient biocatalyst
      recycling.

PMID- 23880443
TI  - Elevated acetaminophen concentration measured after nasal insufflation of
      Percocet(r).
AB  - BACKGROUND: Prescription opioid products are often formulated with acetaminophen,
      but the pharmacokinetics of nasally administered acetaminophen are poorly
      characterized. We report a case of a potentially toxic acetaminophen
      concentration after nasal insufflation of oxycodone/acetaminophen tablets. CASE
      REPORT: A 38-year-old female presented to the emergency department after 2 days
      of nasally insufflating a total of 50 oxycodone/acetaminophen 5/325 mg tablets.
      On day 3, she was evaluated for nausea and pharyngitis. She denied oral ingestion
      of the drug. The initial acetaminophen concentration was 14 MUg/mL, although the
      patient had not insufflated any medication in approximately 24 h. Initial AST and
      ALT were normal. The patient was treated with a 21-h course of intravenous N
      acetylcysteine. On hospital day 2, the measured acetaminophen concentration was <
      10 MUg/mL and the patient's liver enzymes remained within normal limits.
      CONCLUSIONS: The pharmacokinetics of nasally administered acetaminophen have not
      been well studied, yet there is potential for significant exposure with
      prescription opioid abuse. Clinicians should be vigilant in evaluating patients
      for toxicity due to adjunct medications formulated in narcotic pain preparations
      used by routes other than ingestion.

PMID- 23880444
TI  - Traffic jam in the duodenum: imaging and pathogenesis of Bouveret syndrome.

PMID- 23880445
TI  - A young military recruit with unilateral atypical swelling of his left arm:
      malingering revisited.

PMID- 23880446
TI  - A child with altered sensorium, hyperglycemia, and elevated troponins.
AB  - BACKGROUND: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state
      (HHS) are potentially life-threatening complications of diabetes mellitus.
      Although DKA and HHS share similar features, they are distinct clinical entities
      requiring different treatment measures. OBJECTIVE: This case illustrates that the
      clinical distinction between these two entities can be difficult at times,
      especially in children who can present with an overlapping picture. CASE REPORT:
      We report an interesting case of a 12-year-old whose initial presentation of
      diabetes was a mixed picture of hyperosmolar DKA and HHS coma complicated by
      myocardial strain and acute renal insufficiency. The myocardial strain resolved
      completely with resolution of the metabolic abnormalities. CONCLUSIONS: Emergency
      physicians should be cognizant of varied presentations of hyperglycemic
      emergencies in children to initiate appropriate management for better outcomes.

PMID- 23880447
TI  - Mid-gut volvulus identified by pediatric emergency ultrasonography.

PMID- 23880448
TI  - The impact of childhood adversity on suicidality and clinical course in treatment
      resistant depression.
AB  - BACKGROUND: Childhood adversity is a risk factor for the development of
      depression and can also affect clinical course. We investigated this specifically
      in treatment-resistant depression (TRD). METHODS: One hundred and thirty-seven
      patients with TRD previously admitted to an inpatient affective disorders unit
      were included. Clinical, demographic and childhood adversity (physical, sexual,
      emotional abuse; bullying victimization, traumatic events) data were obtained
      during admission. Associations between childhood adversity, depressive symptoms
      and clinical course were investigated. RESULTS: Most patients had experienced
      childhood adversity (62%), with traumatic events (35%) and bullying victimization
      (29%) most commonly reported. Childhood adversity was associated with poorer
      clinical course, including earlier age of onset, episode persistence and
      recurrence. Logistic regression analyses revealed childhood adversity predicted
      lifetime suicide attempts (OR 2.79; 95% CI 1.14, 6.84) and childhood physical
      abuse predicted lifetime psychosis (OR 3.42; 95% CI 1.00, 11.70). LIMITATIONS:
      The cross-sectional design and retrospective measurement of childhood adversity
      are limitations of the study. CONCLUSIONS: Childhood adversity was common amongst
      these TRD patients and was associated with poor clinical course, psychosis and
      suicide attempts. Routine assessment of early adversity may help identify at risk
      individuals and inform clinical intervention.

PMID- 23880449
TI  - The cushioning properties of athletic socks: an impact testing perspective.
AB  - BACKGROUND: One of the aims of the sock/shoe unit is to reduce the severity of
      impact forces on the lower extremity although the injury prevention potential of
      the sock through the attenuation of impact force has yet to be established. This
      study aims to determine the effect of athletic socks and a sock/shoe unit on peak
      impact force, time to peak impact force and loading rate using an impact testing
      methodology. METHODS: An impact testing system with a gravity driven vertical
      impact striker (8.5kg) fitted with a load cell (10,000Hz) which was released from
      0.05m to impact the specimen on the vertical axis (impact velocity=0.99m.s(-1))
      was used throughout the study. FINDINGS: All socks reduced peak impact force by
      between 6% and 20% when compared to a no sock control condition. Furthermore,
      large significant correlation coefficients (r=.62 to .72) were observed between
      thickness and peak impact force, time to peak impact force and loading rate in
      the sock only condition. INTERPRETATION: Athletic socks demonstrate cushioning
      properties under impact testing conditions.

PMID- 23880450
TI  - Novel Norovirus GII.4 Variant, Shanghai, China, 2012.

PMID- 23880451
TI  - Cloning and characterization of a clip domain serine protease and its homolog
      (masquerade) from Eriocheir sinensis.
AB  - Serine proteinases (SPs) or SP homologs (SPHs) including clip domain SPs (cSPs)
      or SPHs (cSPHs) play critical roles in digestion, embryonic development,
      hemolymph coagulation, and melanization. In this study, one cSP (EscSP) and one
      SPH, similar to Drosophila masquerade (EsMas), were identified from
      hepatopancreas of the Chinese mittern crab Eriocheir sinensis. They both possess
      the clip domains at the N-terminal, EscSP has only one clip domain, but EsMas has
      seven clip domains. One SP or SP-like domain was at the C-terminal of EscSP and
      EsMas respectively. In contrast to EscSP, absence of a catalytic residue of Ser
      resulted in the loss of SP activity of EsMas. Tissue distribution analysis showed
      that EscSP mRNA was mainly expressed in hepatopancreas, nerve and eyestalk
      tissue; whereas the EsMas transcript was mainly distributed in eyestalk, muscle,
      nerve and hemocytes. EscSP in hemocytes showed significant increase after a
      lipopolysaccharide (LPS) or peptidoglycan (PGN) challenge. However, down
      regulation of EsMas was observed in hemocytes challenged by LPS from 2 to 24 h,
      by contrast EsMas could be induced by PGN challenge at 2 and 24 h. All these
      findings indicated that EscSP and EsMas might be involved in the innate immune
      defenses in E. sinensis. 

PMID- 23880452
TI  - Two thioredoxin-superfamily members from sea bass (Dicentrarchus labrax, L.):
      characterization of PDI (PDIA1) and ERp57 (PDIA3).
AB  - PDI (PDIA1) and ERp57 (PDIA3), members of the PDI family and of the thioredoxin
      (Trx) superfamily, are multifunctional proteins with wide physiological roles and
      have been implicated in several pathologies. Importantly, they are both involved
      in the MHC class I antigen presentation pathway. This paper reports the isolation
      and characterization of full cDNA and genomic clones from sea bass (Dicentrarchus
      labrax, L.) PDI (Dila-PDI) and ERp57 (Dila-ERp57). The genes are ~12.4 and ~7.1
      kb long, originating 2155 and 2173 bp transcripts and encoding 497 and 484 amino
      acids mature proteins, for Dila-PDI and -ERp57, respectively. The PDI gene
      consists of eleven exons and ERp57 of thirteen. As described in other species,
      both molecules are composed of four Trx-like domains (abb'a') followed by a C
      terminal tail, retaining two CGHC active sites and an ER-signalling sequence,
      suggestive of a conserved function. Additionally, three-dimensional homology
      models further support Dila-PDI and Dila-ERp57 as orthologs of mammalian PDI and
      ERp57, respectively. Finally, high similarity is observed to their vertebrate
      counterparts (>69% identity), especially among the few ones from closely related
      teleosts (>79% identity). Hence, these results provide relevant primary data and
      will enable further studies to clarify the roles of PDI and ERp57 in European sea
      bass immunity.

PMID- 23880453
TI  - Molecular characterization and expression analysis of Toll-like receptor 21 cDNA
      from Paralichthys olivaceus.
AB  - Toll-like receptor (TLR) is believed to play crucial role in host defense of
      pathogenic microbes in innate immune system. In the present study, the full
      length cDNA of Paralichthys olivaceus Toll-like receptor 21 (Po-TLR21) was cloned
      by homology cloning and rapid amplification of cDNA ends (RACE) technique. The Po
      TLR21 cDNA sequence was 3687 bp, containing an open reading frame of 2922 bp
      encoding 973 amino acids. TMHMM and SMART program analysis indicated that protein
      contained one transmembrane domain, eighteen leucine-rich repeats (LRRs), and one
      Toll/IL-1 receptor homology domain (TIR). Multiple alignment analysis of the Po
      TLR21 protein-coding sequence with other known TLR21 from grouper, pufferfish,
      zebrafish, cod, catfish, carp and chicken showed the homology of 67%, 63%, 54%,
      52%, 51%, 49%, and 39%, respectively. The Po-TLR21 mRNA expression patterns were
      measured by real-time PCR. The results revealed that TLR21 is widely expressed in
      various tested healthy tissues, and highly expressed in spleen and gill. In vivo
      immunostimulation experiments revealed that expression of TLR21 is modulated by
      Vibrio anguillarum (V. anguillarum), CpG oligodeoxynucleotides (CpG ODN) and poly
      I:C. Moreover, the inhibitor of homodimerization of myeloid differentiation
      factor 88 (MyD88) could significantly reduce the up-regulation of TLR21, MyD88,
      and tumor necrosis factor (TNF) expression in CpG ODN or poly I:C-treated head
      kidney cells in vitro. These results indicate that TLR21 may be involved in the
      pathogen recognition in the early innate immune. 

PMID- 23880454
TI  - Is it mandatory to carry out completion arteriography after carotid
      endarterectomy with patch angioplasty?
AB  - BACKGROUND: This study compares the neurologic evolution and number of restenoses
      between 2 groups of patients who underwent internal carotid endarterectomy with
      patch angioplasty (CEP): one group with systematic intraoperative completion
      arteriography (CA) and another group without. METHODS: This monocentric
      retrospective study was performed from January 2000 to December 2008 on 559
      consecutive CEPs; 179 were controlled with CA and 380 were not. Surgery was
      chosen for patients with greater than 50% symptomatic or greater than 60%
      asymptomatic stenosis (North American Symptomatic Carotid Endarterectomy Trial
      criteria). Each patient's neurologic and ultrasound status was followed-up
      postoperatively, and at 3 months in the presence of neurologic symptoms, and at
      the end of the follow-up. Residual stenosis and restenosis were defined by a
      reduction in diameter of greater than 50% or a maximal systolic velocity greater
      than 150 cm/s. The surgical team included 4 vascular surgeons: 2 experienced
      surgeons who did not perform CA, 1 experienced surgeon monitoring surgical
      trainees, and 1 who had little experience performing CA. RESULTS: In both groups,
      the patients were comparable in terms of cardiovascular risks, except for age,
      gender, statin treatment, and neoplastic medical history. During the first 30
      postoperative days, the mean rate of cerebrovascular accident (CVA) and death was
      0.4%. In the CA group, 1 incidence (0.6%) of partial monocular blindness
      occurred, and in the no-CA group, 1 incidence (0.2%) of hemorrhagic CVA and 3
      (0.5%) transient ischemic attacks (TIAs) occurred. One of these TIAs resulted
      from a residual stenosis. Mean follow-up was 41 months. During this time, 6
      ipsilateral neurologic accidents occurred in the CA group (1 ischemic CVA, 3
      TIAs, 1 partial monocular blindness, and 1 hemorrhagic CVA), whereas 10 occurred
      in the no CA group (1 ischemic CVA, 4 TIAs, 3 hemorrhagic CVAs, 1 partial
      monocular blindness, and 1 recurrence of vertebrobasilar insufficiency). The
      combined morbidity and mortality rates in the 2 groups were 3.3% and 2.8%,
      respectively (P > 0.05). Two residual stenoses (0.5%) and 6 significant
      restenoses (1.6%) were diagnosed in the no-CA group; 4 significant restenoses
      (2.2%) occurred in the CA group (P > 0.05). CONCLUSIONS: When performed by
      experienced surgeons, systematic intraoperative CA does not reduce the incidence
      of ipsilateral neurologic complications after CEP. Systematic intraoperative
      arteriography enables surgical trainees to obtain results as satisfactory as
      those of experienced surgeons.

PMID- 23880455
TI  - A comparison of immediate postoperative rigid and soft dressings for below-knee
      amputations.
AB  - BACKGROUND: A variety of postsurgical dressings are used after a below-knee
      amputation (BKA), but there is no evidence-based guideline on which dressing to
      use. The purpose of this study was to compare the application of immediate
      postoperative rigid dressings or soft dressings on the healing times of BKA.
      METHODS: In this retrospective analysis we compared 151 patients who underwent
      BKA from 2000 to 2012 at Yale New Haven Hospital. Patient demographics were
      collected and the type of postoperative dressing utilized was recorded. Ninety
      one patients received a rigid plaster or plastic dressing and 60 received a soft
      gauze dressing with knee immobilizer. Time was measured between amputation and
      initial casting of prosthesis. RESULTS: Average age for the rigid dressing group
      was 58.6 years, with 78.2% presenting with diabetes mellitus, compared with the
      soft dressing group of 61.0 years, with 82.8%, respectively. Using a Kaplan-Meier
      analysis, patients fit with a rigid dressing demonstrated significantly decreased
      healing time from BKA to initial casting for a prosthesis (P = 0.02). After the
      first 60 days, 58.24% of patients who received a rigid dressing were ready to be
      cast, compared with 38.33% of patients receiving a soft dressing (P = 0.03).
      CONCLUSIONS: Below-knee amputees had a significantly quicker healing time, as
      measured by the time to be cast for prosthesis, when a rigid dressing was used
      compared with a soft dressing. Consideration should be given to the use of a
      rigid dressing after BKA to expedite healing and promote earlier ambulation.

PMID- 23880456
TI  - Evaluation of balloon catheter-guided intra-arterial thrombolysis for acute
      peripheral arterial occlusion.
AB  - BACKGROUND: The objective of this study was to evaluate the effectiveness of a
      new method of in situ thrombolysis using a porous balloon with low pressure
      compared with traditional in situ infusion of a fibrinolytic agent in the
      treatment of acute limb ischemia. METHODS: Between January 2010 and December
      2011, 14 patients (mean age, 67.2 years; range, 40-89 years) treated for grade II
      acute lower limb ischemia for fewer than 14 days were included in the study.
      Thromboaspiration was tried initially in all the cases. All patients benefitted
      from a novel method of intra-arterial thrombolysis guided with a balloon catheter
      (ClearWay; Atrium Medical, Hudson, NH) and using the same agent thrombolytic
      (Actosolv). The total amount injected, the rate of morbidity associated with the
      thrombolytic treatment, and the duration of hospitalization in the continuous
      monitoring unit were analyzed. RESULTS: Recanalization was obtained in 92% of
      cases (13 of 14). The rate of morbidity related to the procedure was 7%. The
      amount of fibrinolytic agent necessary was relatively low (82,000 units/cm of
      occluded artery). The rate of limb salvage 6 months after recanalization was of
      92%. The mean duration of stay in the continuous monitoring unit was 1.1 day.
      CONCLUSIONS: Intra-arterial thrombolysis using the ClearWay balloon catheter is
      an effective method in the treatment of acute peripheral arterial occlusion. In
      the event of embolic occlusion, mainly among very old patients, it could decrease
      the hemorrhagic risk. A randomized study in these high-risk patients could
      confirm these first results.

PMID- 23880457
TI  - Hyperbaric oxygen decreases intimal thickness and area after carotid artery
      balloon injury in a rat model.
AB  - BACKGROUND: Clinical studies have suggested a benefit for hyperbaric oxygen (HBO)
      treatment in decreasing symptomatic restenosis after coronary angioplasty. We
      hypothesize that HBO treatment will decrease hyperplastic intimal area after
      arterial balloon injury in a rat. METHODS: Fifty-four male Sprague-Dawley rats
      (Charles River Laboratories, Wilmington, MA) were randomly assigned either to
      room air (n = 27) or a treatment group (n = 27) receiving HBO treatment (2
      hyperbaric treatments of 100% oxygen at 2 bars for 90 min). A 2F balloon-tipped
      catheter was used to injure the right common carotid arteries, which were
      harvested at 7, 14, and 28 days. Postinjury intimal thickness and area were
      measured from hematoxylin-eosin-stained specimens at each time point. Computer
      assisted histomorphometry was used to calculate maximal intimal thickness,
      relative intimal thickness (ratio of intimal to intimal plus medial thickness),
      intimal area, and the intimal to medial area ratio. RESULTS: There was a 42.3%
      reduction in maximal intimal thickness (P = 0.0012) and a 36.5% reduction in
      intimal area (P = 0.0337) at day 28 in the HBO-treated group (mean +/- standard
      error [SE], 0.0425 +/- 0.0054 mm for maximal thickness and 0.065 +/- 0.0056 mm(2)
      for area) when compared to the normoxic group (0.0737 +/- 0.004 mm for maximal
      thickness and 0.0413 +/- 0.0074 mm(2) for area). The relative intimal thickness
      also showed a 28.3% reduction at day 28 in the HBO-treated group (ratio of 0.38
      +/- 0.0329) compared to the normoxic group (ratio of 0.53 +/- 0.0141; P =
      0.0065). CONCLUSIONS: Our results indicate that HBO treatment decreases maximal
      intimal thickness and intimal area of the carotid artery after balloon injury.
      This could have significant clinical implications on the increasing number of
      endovascular interventions in vascular surgery and cardiology.

PMID- 23880458
TI  - Morphologic and biomechanical changes of thoracic and abdominal aorta in a rat
      model of cigarette smoke exposure.
AB  - BACKGROUND: Smoking is the most relevant environmental factor that affects the
      development of aortic aneurysm. Smokers have elevated levels of elastase activity
      in the arterial wall, which leads to weakening of the aorta. The aim of this
      study was to verify whether cigarette smoke exposure itself is capable of
      altering the aortic wall. METHODS: Forty-eight Wistar rats were divided into 2-,
      4-, and 6-month experimental periods and into 2 groups: smokers (submitted to
      smoke exposure at a rate of 40 cigarettes/day) and nonsmokers. At the end of the
      experimental periods, the aortas were removed and cross-sectioned to obtain
      histologic specimens for light microscopic and morphometric analyses. The
      remaining longitudinal segments were stretched to rupture and mechanical
      parameters were determined. RESULTS: A degenerative process (i.e., a reduction in
      elastic fibers, the loss of lamellar arrangement, and a reduction of smooth
      muscle cells) was observed, and this effect was proportional in intensity to the
      period of tobacco exposure. We observed a progressive reduction in the yield
      point of the thoracic aorta over time (P < 0.05). There was a decrease in
      stiffness (P < 0.05) and in failure load (P < 0.05) at 6 months in the abdominal
      aorta of rats in the smoking group. CONCLUSIONS: Chronic exposure to tobacco
      smoke can affect the mechanical properties of the aorta and can also provoke
      substantial structural changes of the arterial wall.

PMID- 23880459
TI  - Diagnosis and treatment of Parkes Weber syndrome: a review of 10 consecutive
      patients.
AB  - BACKGROUND: We sought to retrospectively analyze the clinical presentation,
      diagnosis, treatment, and outcomes of patients with Parkes Weber syndrome (PWS)
      who were treated at a single institution. METHODS: A retrospective review was
      conducted of medical records of all patients with PWS treated at La Paz
      Children's Hospital between 1994 and 2010. RESULTS: Ten patients (median age,
      14.8 years [range, 2-52 years]) were identified, including 7 women and 3 men. Six
      patients presented with lower limb hypertrophy and capillary malformation at
      birth, and both the right and left lower extremities were equally involved.
      Severe tricuspid insufficiency was observed in 1 patient. The median dysmetria
      between both lower extremities was 2.19 cm. Four patients are being treated
      successfully with compression garment therapy. Three patients underwent resection
      of multiple arteriovenous nidus. Three patients had palliative embolizations. One
      patient required above the knee amputation secondary to ischemia and chronic
      severe pain. CONCLUSIONS: The early recognition of PWS is required to establish
      the most appropriate treatment and prevent short-term morbidity and unnecessary
      invasive diagnostic tests. Treatment should be individualized according to the
      age and clinical features of each patient. Although initial conservative
      management is recommended, surgery continues to play an important role in order
      to improve the quality of life in these patients.

PMID- 23880460
TI  - Mycotic aneurysm of the internal carotid artery.
AB  - BACKGROUND: Infected aneurysms of the extracranial carotid arteries are uncommon.
      This article presents a complete review of the literature on this condition,
      illustrated with a case report. This case report describes a mycotic aneurysm of
      carotid bifurcation with proven infection of the arterial wall from Salmonella
      enteritidis. The treatment consisted of excision of the aneurysm, ligation of the
      external carotid, and realization of a common to internal carotid artery bypass
      with the greater saphenous vein. METHODS: In August 2012, the authors searched
      the PubMed database with the keywords "carotid artery pseudoaneurysm" and
      "mycotic carotid aneurysm" for the period until 2012. RESULTS: The incidence of
      extracranial infected carotid artery aneurysm is relatively stable, with
      approximately 20 cases reported per decade over the past 30 years. The authors
      analyzed approximately 100 cases reported in the literature and studied the
      origin of the condition and the evolution of surgical options.

PMID- 23880461
TI  - Remodeling of human red cells infected with Plasmodium falciparum and the impact
      of PHIST proteins.
AB  - In an infected erythrocyte (iRBC), renovation and decoration are crucial for
      malarial parasite survival, pathogenesis and reproduction. Host cell remodeling
      is mediated by an array of diverse parasite-encoded export proteins that traffic
      within iRBC. These remodeling proteins extensively modify the membrane and
      cytoskeleton of iRBC and help in formation of parasite-induced novel organelles
      such as 'Maurer's Cleft (MC), tubulovesicular network (TVN) and parasitophorous
      vacuole membrane (PVM) inside the iRBC. The genome sequence of Plasmodium
      falciparum shows expansion of export proteins, which suggests a complex
      requirement of these export proteins for specific pathogenesis and erythrocyte
      remodeling. Plasmodium helical intersperse sub-telomeric (PHIST) is a family of
      seventy-two small export proteins and many of its recently discovered functional
      characteristics suggest an intriguing putative role in modification of an iRBC.
      This review highlights the recent advances in parasite genomics, proteomics, and
      cell biology studies unraveling the host cell modification; providing a
      speculation on the impact of PHIST proteins in modification of the iRBC. 

PMID- 23880462
TI  - The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct
      functions in mitochondrial dynamics.
AB  - Mitochondria are dynamic organelles whose morphology is regulated by a complex
      balance of fission and fusion processes, and we still know relatively little
      about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has
      recently been characterized as a key regulator of mitochondrial dynamics and in
      this report we explore the functions of its paralog MIEF2 (also called MiD49), to
      learn to what extent MIEF2 is functionally distinct from MIEF1. We show that
      MIEF1 and MIEF2 have many functions in common. Both are anchored in the
      mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the
      mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can
      interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain
      aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during
      development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect
      than MIEF1, and in line with this, hFis1 and Mff can only partially revert the
      MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a
      larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers,
      while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use
      distinct domains for oligomerization: in MIEF1, the region from amino acid
      residues 109-154 is required, whereas oligomerization of MIEF2 depends on amino
      acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization
      of MIEF1 is not required for its mitochondrial localization and interaction with
      Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and
      MIEF2 exert partially distinct functions in mitochondrial dynamics. 

PMID- 23880463
TI  - The multi-PDZ domain protein-1 (MUPP-1) expression regulates cellular levels of
      the PALS-1/PATJ polarity complex.
AB  - MUPP-1 (multi-PDZ domain protein-1) and PATJ (PALS-1-associated tight junction
      protein) proteins are closely related scaffold proteins and bind to many common
      interactors including PALS-1 (protein associated with Lin seven) a member of the
      Crumbs complex. Our goal is to understand how MUPP-1 and PATJ and their
      interaction with PALS-1 are regulated in the same cells. We have shown that in
      MCF10A cells there are at least two different and co-existing complexes, PALS
      1/MUPP-1 and PALS-1/PATJ. Surprisingly, MUPP-1 levels inversely correlated with
      PATJ protein levels by acting on the stabilization of the PATJ/PALS-1 complex.
      Upon MUPP-1 depletion, the increased amounts of PATJ are in part localized at the
      migrating front of MCF10A cells and are able to recruit more PAR3 (partition
      defective 3). All together these data indicate that a precise balance between
      MUPP-1 and PATJ is achieved in epithelial cells by regulating their association
      with PALS-1.

PMID- 23880464
TI  - Separation and purification of bovine serum albumin binders from Fructus polygoni
      orientalis using off-line two-dimensional complexation high-speed counter-current
      chromatography target-guided by ligand fishing.
AB  - In this study, off-line two-dimensional (2D) complexation high speed counter
      current chromatography (HSCCC) was developed for the separation of bovine serum
      albumin (BSA) binders from the ethyl acetate extract of Fructus polygoni
      orientalis. Target-guided strategy of BSA functionalized iron oxide magnetic
      nanoparticles coupled with high performance liquid chromatography-tandem mass
      spectrometry ((BSA-Fe3O4 MNPs)-HPLC-MS/MS) experiment was proposed. In the
      orthogonal separation system, a Normal-Phase HSCCC with 0.01mol/L copper ion as
      complexation agent in the aqueous phase was employed for the first dimension and
      Recycling HSCCC, Reverse-Phase HSCCC with 0.1mol/L copper ion were used for the
      second dimension in parallel. Including two pairs of cis-trans isomers, seven BSA
      binders including 3,5,7-Trihydroxychromone (1), taxifolin (2), N-cis-paprazine
      (3), N-cis-feruloyltyramine (4), N-trans-paprazine (5), N-trans-feruloyltyramine
      (6) and an unidentified compound (7) were obtained. The purities of these seven
      compounds were all over 95.0% as determined by HPLC. The complexation HSCCC
      behaviors of seven compounds were also investigated by studying their
      relationship with copper ion. Results showed that the combinative method using
      (BSA-Fe3O4 MNPs)-HPLC and HSCCC is a quick, efficient, and reproductive technique
      to isolate potentially bioactive compounds from the complex mixture system of
      natural products. And the usage of off-line 2D-HSCCC and introduction of
      chelating metal ion into solvent system are effective ways to implement HSCCC
      separations in complex samples. 

PMID- 23880465
TI  - Improved assessment of pyrogenic carbon quantity and quality in environmental
      samples by high-performance liquid chromatography.
AB  - The analysis of pyrogenic carbon (PyC) in environmental samples is of great
      interest, e.g. for carbon cycle assessment, (bio-)char characterization and
      palaeo-environmental or archeological reconstruction. Here, an HPLC method (HPLC)
      is presented that reproducibly quantifies benzene polycarboxylic acids (BPCA) as
      molecular markers for PyC in various kinds of environmental samples. It operates
      at low pH without requiring an organic modifier and was thoroughly tested with
      PyC reference materials and a peatland core that served as a feasibility and
      plausibility check. Compared to the established gas chromatography (GC) method,
      the HPLC method results in higher BPCA quantification reproducibility by showing
      a significantly smaller coefficient of variation (HPLC: 5%, GC: 16-23%). It works
      well with small sample amounts, as for instance from sediment cores and aerosol
      collectors, and requires less sample preparation work than the GC method.
      Moreover, the here presented HPLC method facilitates (13)C and (14)C analyses on
      PyC from environmental samples. 

PMID- 23880466
TI  - Retention behavior of proton pump inhibitors using immobilized polysaccharide
      derived chiral stationary phases with organic-aqueous mobile phases.
AB  - In the present study, the chromatographic behavior of two immobilized
      polysaccharide-derived chiral stationary phases (CSPs), the Chiralpak ID-3 and
      Chiralpak IE-3, under aqueous mobile phases conditions is presented. Four proton
      pump inhibitors (PPIs) (omeprazole, lansoprazole, pentaprazole and rabeprazole)
      were selected as test compounds. The effect of the concentration of water in the
      mobile phase was investigated with respect to its contribution to
      enantioselectivity and retention. Under acetonitrile-water mobile phase
      conditions, retention behavior evidenced an interesting pattern. At lower water
      content, the retention factors decreased with increasing water and at higher
      water content a reversed trend was observed. These findings support the
      hypothesis that two retention mechanisms operated successively on the same CSP:
      the HILIC (with water-poor eluents) and RPLC (with water-rich eluents) modes. The
      retention factors were minimum in the intermediate region, corresponding to a
      water concentration of about 20%. Interestingly, the baseline separation of all
      PPIs investigated was optimized under organic-aqueous mobile phases containing a
      high water content (from about 50 to 65%). Thus, the dual retention behavior of
      the PPIs on the Chiralpak ID-3 and Chiralpak IE-3 made it possible to reach
      greener and harmless enantioselective conditions in a short analysis time. 

PMID- 23880467
TI  - Ultra-high performance liquid chromatography coupled with photo-diode array and
      quadrupole/time-of-flight mass spectrometry based chemical profiling approach to
      evaluate the influence of preparation methods on the holistic quality of Qiong-Yu
      Gao, a traditional complex herbal medicine.
AB  - Qiong-Yu-Gao (QYG), consisting of Rehmanniae Radix (RR), Poriae (PO) and Ginseng
      Radix (GR), is a commonly used tonic traditional complex herbal medicine (CHM).
      So far, three different methods have been documented for preparation of QYG, i.e.
      method 1 (M1): mixing powders of GR and PO with decoction of RR; method 2 (M2):
      combining the decoction of RR and PO with the decoction of GR; method 3 (M3):
      decocting the mixture of RR, GR and PO. In present study, an ultra-high
      performance liquid chromatography coupled with photo-diode array and
      quadrupole/time-of-flight mass spectrometry (UHPLC-PDA-QTOF-MS/MS) based chemical
      profiling approach was developed to investigate the influence of the three
      preparation methods on the holistic quality of QYG. All detected peaks were
      unambiguously identified by comparing UV spectra, accurate mass
      data/characteristic mass fragments and retention times with those of reference
      compounds, and/or tentatively assigned by matching empirical molecular formula
      with that of known compounds, and/or elucidating quasi-molecular ions and
      fragment ions referring to information available in literature. A total of 103
      components, mainly belonging to ginsenosides, phenethylalcohol glycosides,
      iridoid glycosides and triterpenoid acids, were identified, of which 5 degraded
      ginsenosides were putatively determined to be newly generated during preparation
      procedures of QYG samples. Triterpenoid acids and malonyl-ginsenosides were
      detected only in M1 samples, while degraded ginsenosides were merely detectable
      in M2/M3 samples. The possible reasons for the difference among chemical profiles
      of QYG samples prepared with three methods were also discussed. It could be
      concluded that preparation method do significantly affect the holistic quality of
      QYG. The influence of the altered chemical profiles on the bioactivity of QYG
      needs further investigation. The present study demonstrated that UHPLC-PDA-QTOF
      MS/MS based chemical profiling approach is efficient and reliable for evaluating
      the holistic quality of traditional CHM. 

PMID- 23880468
TI  - Nano-liquid chromatography in nutraceutical analysis: determination of
      polyphenols in bee pollen.
AB  - In this study, a nano-liquid chromatography based method for the simultaneous
      separation of 16 polyphenols employing UV-vis detection has been developed. A 100
      MUm I.D. capillary column packed with C18 core-shell particles (2.6 MUm particle
      size, 100 A) for 10 cm was employed. The separation of analytes was performed
      with a step gradient in less than 20 min, using 0.5% formic acid aqueous solution
      and acetonitrile as eluents. The optimized analytical method was validated and
      the resulting RSD% for intra-day and inter-day repeatability, related to
      retention time, retention factor and peak area, were below 4.68 and 5.57%,
      respectively. LOD and LOQ values were as low as 0.78 and 3.12 MUg/mL, while
      linearity, assessed in the concentration range of interest for all analytes, gave
      R(2)>=0.990. The method was finally applied to the analysis of polyphenols
      extracted from a collected bee pollen. Nine polyphenols, namely o-, p-coumaric
      acid, ferulic acid, myricetin, cinnamic acid, quercetin, naringenin, hesperitin
      and kaempferol, were identified. All analytes, with the exception of p-coumaric
      acid and myricetin, which partially co-eluted with other pollen components, were
      also quantified in the sample.

PMID- 23880469
TI  - Characterization of diacylglycerol isomers in edible oils using gas
      chromatography-ion trap electron ionization mass spectrometry.
AB  - Verifying the authenticity of edible oils is of international concern. A new
      quality control standard for olive oil has been proposed that relates the ratio
      of 1,2-diacylglycerol (DAG) to 1,3-DAG to sensory aspects of olive oil. DAGs and
      their isomers are difficult to quantitate and characterize by Flame Ionization
      Gas Chromatography (GC-FID) due to the lack of suitable standards. Mass detectors
      offer the advantage of providing structural detail to the eluding DAG(s), thus
      removing ambiguity to the identification of both resolved and unresolved DAGs in
      GC chromatograms. In this study, a GC Electron Ionization Mass Spectrometry (GC
      EI-MS) method was developed to determine the fatty acid composition and molecular
      structure of trimethylsilyl (TMS) derivatized DAGs present in edible oils. Twenty
      two species of DAG isomers were identified in refined coconut oil and unrefined
      olive oil utilizing signature fragment ions, [M-15](+), [M-89](+), [M-RCO2](+),
      [RCO2+58](+) and [M-RCO2CH2](+). The [M-RCO2CH2](+) ion is considered the key
      diagnostic ion to distinguish between DAG positional isomers. MS/MS spectra of [M
      RCO2](+) and [M-15](+) ions obtained from commercial standards containing both
      1,2- and 1,3-DAG isomers were used as a model system to confirm the
      identification of DAG isomers in natural products. Furthermore, a number of
      reaction mechanisms are proposed to explain the formation of the most abundant
      mass fragments of DAGs and their isomers. 

PMID- 23880470
TI  - Fe(3)O(4)@MOF core-shell magnetic microspheres for magnetic solid-phase
      extraction of polychlorinated biphenyls from environmental water samples.
AB  - Fe3O4@MIL-100 core-shell magnetic microspheres were, for the first time, used as
      the sorbent for the magnetic solid-phase extraction (MSPE) of polychlorinated
      biphenyls at trace levels in environmental water samples. GC coupled with tandem
      MS was used for sample quantification and detection. The Box-Behnken design was
      used to determine the optimum extraction parameters influencing extraction
      efficiency through response surface methodology. Under the optimized conditions,
      the developed method showed good linearity within the range of 5-4000ngL(-1), low
      limits of detection (1.07-1.57ngL(-1); signal-to-noise ratio=3:1), and good
      extraction repeatability (relative standard deviation<12%; n=5). Environmental
      samples collected from the Yellow River, local lake, wastewater, and snow water
      were processed using the developed method. The results demonstrated that the
      Fe3O4@MOF core-shell magnetic microspheres are promising sorbents in the MSPE of
      aromatic pollutants from environmental water samples. 

PMID- 23880471
TI  - Temperature-modulated noncovalent interaction controllable complex for the long
      term delivery of etanercept to treat rheumatoid arthritis.
AB  - The clinical applications of etanercept (Enbrel), an emerging therapeutic protein
      for rheumatoid arthritis (RA), are limited by its instability and low
      bioavailability. In this study, a long-term and efficient therapeutic nanocomplex
      formulation for RA treatment was developed in the form of a temperature-modulated
      noncovalent interaction controllable (TMN) complex based on a temperature
      sensitive amphiphilic polyelectrolyte (succinylated pullulan-g-oligo(L-lactide);
      SPL). The TMN complexes were prepared by simply mixing the negatively charged SPL
      copolymer and the positively charged etanercept via electrostatic interaction at
      4  degrees C below the polymer's clouding temperature (CT), and the resulting
      complex demonstrated significantly improved salt and serum stability with
      increased hydrophobic interactions at temperatures (physiological condition, 37.5
      degrees C) above the CT. An in vitro study of the bioactivity of etanercept
      indicated that the TMN complex improves the long-term stability of etanercept in
      an aqueous environment because of the exposure of the functional active site and
      the molecular chaperone-like effect of the hydrophobic copolymer. This
      formulation possessed prolonged in vivo pharmacokinetic parameters. In a collagen
      induced arthritis RA rat model, we verified the outstanding therapeutic effect of
      the TMN complexes. These results imply that this approach would be widely applied
      to protein and peptide delivery systems.

PMID- 23880472
TI  - Targeting HER2+ breast cancer cells: lysosomal accumulation of anti-HER2
      antibodies is influenced by antibody binding site and conjugation to polymeric
      nanoparticles.
AB  - Humanized monoclonal antibodies (mAb) against HER2 are being engineered to treat
      cancer. We utilized phage-display technology to generate a novel anti-HER2 mAb
      (named 73JIgG) that binds an epitope of HER2 distinct from that of trastuzumab.
      Although these mAbs bind to the same cell surface receptor, they have different
      cell distribution profiles. After 3h of incubation, almost 10% of the total
      73JIgG reaches the lysosome compared to less than 3% of trastuzumab.
      Interestingly, 73JIgG disassociates from HER2 whereas trastuzumab remains bound
      to the receptor. Importantly, HER2 distribution is not affected by the antibody
      binding epitope, thus negating this mechanism as the reason for the difference in
      intracellular trafficking of 73JIgG versus trastuzumab. Each of trastuzumab and
      73JIgG was chemically-modified with either a small molecule or polymeric
      nanoparticle to better understand the influence of conjugation on cellular
      localization. Relative to antibody alone, antibody-nanoparticle conjugates
      resulted in a higher concentration of antibodies in the lysosome whereas antibody
      small molecule conjugates did not affect cell trafficking to the lysosome. Given
      the importance of lysosomal targeting, these results demonstrate the importance
      of understanding the influence of the antibody-conjugate on cell trafficking for
      ultimate optimization of treatment selection. 

PMID- 23880474
TI  - Low-dose metronomic chemotherapy: a systematic literature analysis.
AB  - Low-dose metronomic (LDM) chemotherapy, the frequent and continuous use of low
      doses of conventional chemotherapeutics, is an emerging alternative to
      conventional chemotherapy. While promising tumour control rates and excellent
      safety profiles have been observed, there are no definitive phase III trial
      results. Furthermore, the selection of patients, drug dosages and dosing
      intervals is empirical. To systematically review the current state of knowledge
      regarding LDM chemotherapy, we searched the MEDLINE, EMBASE, CENTRAL and PubMed
      databases for fully published LDM chemotherapy trials. We calculated the relative
      dose-intensity (RDI, mg/m(2)/week) of each LDM regimen as compared to
      conventional maximum tolerated dose (MTD) dosages and the 'dosing-density' (DD, %
      of days with chemotherapy administration per cycle). Meta-regression was
      performed to examine factors associated with disease control rate (DCR; complete
      response (CR)+partial response (PR)+stable disease (SD)). Eighty studies
      involving mainly pretreated patients with advanced/metastatic breast (26.25%) and
      prostate (11.25%) cancers were retrieved. The most commonly used drug was
      cyclophosphamide (43%). LDM chemotherapy was frequently combined with other
      therapies (64.5%). Response rate (RR) and progression-free survival (PFS) were
      the most frequent primary end-points (24% and 19%). Mean RR was 26.03% (95%
      confidence interval (CI): 21.4-30.7), median PFS was 4.6months (interquartile
      range (IQR): 2.9-7.0) and mean DCR was 56.3% (95% CI: 50.9-61.6). RDI, DD and
      metronomic drug used were not associated with DCR. Grade 3/4 adverse events were
      rare (anaemia 7.78%, fatigue 13.4%). Thus, LDM therapy appears to be clinically
      beneficial and safe in a broad range of tumors. However, meta-regression analysis
      did not identify predictive factors of response. 

PMID- 23880473
TI  - Superficial dosimetry imaging of Cerenkov emission in electron beam radiotherapy
      of phantoms.
AB  - Cerenkov emission is generated from ionizing radiation in tissue above 264 keV
      energy. This study presents the first examination of this optical emission as a
      surrogate for the absorbed superficial dose. Cerenkov emission was imaged from
      the surface of flat tissue phantoms irradiated with electrons, using a range of
      field sizes from 6 cm * 6 cm to 20 cm * 20 cm, incident angles from 0 degrees  to
      50 degrees , and energies from 6 to 18 MeV. The Cerenkov images were compared
      with the estimated superficial dose in phantoms from direct diode measurements,
      as well as calculations by Monte Carlo and the treatment planning system.
      Intensity images showed outstanding linear agreement (R(2) = 0.97) with reference
      data of the known dose for energies from 6 to 18 MeV. When orthogonal delivery
      was carried out, the in-plane and cross-plane dose distribution comparisons
      indicated very little difference (+/- 2-4% differences) between the different
      methods of estimation as compared to Cerenkov light imaging. For an incident
      angle 50 degrees , the Cerenkov images and Monte Carlo simulation show excellent
      agreement with the diode data, but the treatment planning system had a larger
      error (OPT = +/- 1~2%, diode = +/- 2~3%, TPS = +/- 6-8% differences) as would be
      expected. The sampling depth of superficial dosimetry based on Cerenkov radiation
      has been simulated in a layered skin model, showing the potential of sampling
      depth tuning by spectral filtering. Taken together, these measurements and
      simulations indicate that Cerenkov emission imaging might provide a valuable
      method of superficial dosimetry imaging from incident radiotherapy beams of
      electrons.

PMID- 23880475
TI  - Comments on 'CD44-negative cells in head and neck squamous carcinoma also have
      stem-cell like traits', Se-Yeong Oh et al., European Journal of Cancer, published
      online 6 July 2012.

PMID- 23880477
TI  - The field of pharmacology.

PMID- 23880476
TI  - Clear cell sarcomas of the kidney registered on International Society of
      Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: a report of the SIOP
      Renal Tumour Study Group.
AB  - PURPOSE: Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood renal
      tumour. Only a few homogeneously treated CCSK cohorts have been reported. This
      study aims to describe clinical characteristics and survival of CCSK patients
      treated according to recent International Society of Pediatric Oncology (SIOP)
      protocols. PATIENTS AND METHODS: We analysed the prospectively collected data of
      patients with a histologically verified CCSK, entered onto SIOP 93-01/2001
      trials. RESULTS: A total of 191 CCSK patients (64% male) were analysed, with a
      median age at diagnosis of 2.6 years. Stage distribution for stages I, II, III
      and IV was 42%, 23%, 28% and 7%, respectively. Pre-operative chemotherapy was
      administered to 169/191 patients. All patients underwent total nephrectomy and
      189/191 patients received post-operative chemotherapy. Radiotherapy was applied
      in 2/80 stage I, 33/44 stage II, 44/54 stage III and 6/13 stage IV patients. Five
      year event-free survival (EFS) and overall survival (OS) were 79% (95% confidence
      interval (CI): 73-85%) and 86% (95% CI: 80-92%) respectively. Stage IV disease
      and young age were significant adverse prognostic factors for event-free
      survival. Factors such as gender, tumour volume and type of initial treatment
      were not found to be prognostic for EFS and OS. CONCLUSION: In this largest SIOP
      cohort described so far, overall outcome of CCSK is reasonable, although
      treatment of young and advanced-stage disease patients is challenging. As further
      intensification of treatment is hampered by direct and late toxicity, future
      directions should include the development of targeted therapy based on specific
      molecular aberrations of CCSK.

PMID- 23880478
TI  - Potential impacts of the Alberta fetal alcohol spectrum disorder service networks
      on secondary disabilities: a cost-benefit analysis.
AB  - OBJECTIVES: To estimate the break-even effectiveness of the Alberta Fetal Alcohol
      Spectrum Disorder (FASD) Service Networks in reducing occurrences of secondary
      disabilities associated with FASD. METHODS: The secondary disabilities addressed
      within this study include crime, homelessness, mental health problems, and school
      disruption (for children) or unemployment (for adults). We used a cost-benefit
      analysis approach where benefits of the service networks were the cost difference
      between the two approaches: having the 12 service networks and having no service
      network in place, across Alberta. We used a threshold analysis to estimate the
      break-even effectiveness (i.e. the effectiveness level at which the service
      networks became cost-saving). RESULTS: If no network was in place throughout the
      province, the secondary disabilities would cost $22.85 million (including $8.62
      million for adults and $14.24 million for children) per year. Given the cost of
      network was $6.12 million per year, the break-even effectiveness was estimated at
      28% (range: 25% to 32%). DISCUSSION: Although not all benefits associated with
      the service networks are included, such as the exclusion of the primary benefit
      to those experiencing FASD, the benefits to FASD caregivers, and the preventative
      benefits, the economic and social burden associated with secondary disabilities
      will "pay-off" if the effectiveness of the program in reducing secondary
      disabilities is 28%.

PMID- 23880479
TI  - Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy
      for empiric primary treatment of Helicobacter pylori infection.
AB  - BACKGROUND: In areas with high clarithromycin resistance, bismuth quadruple
      therapy (BQT) is recommended instead of clarithromycin triple therapy (CTT) as
      the first-line treatment for Helicobacter pylori eradication. METHODS: Randomized
      clinical trials (RCTs) comparing BQT to CTT were identified through electronic
      and manual searches. A meta-analysis was performed to compare the efficacy and
      tolerability of these two regimens as first-line treatments for H. pylori
      infection. The effect of antibiotic resistance on treatment efficacy was also
      analyzed. RESULTS: Twelve RCTs were included. BQT achieved eradication in 77.6%
      of patients, whereas CTT achieved an eradication rate of 68.9% [risk difference
      (RD) = 0.06, 95% CI: -0.01/0.13]. A high heterogeneity among the trials was found
      (chi2 = 50.16, p < 0.00001; I2 = 78%). In the subgroup analysis for treatment
      duration, the 10-day BQT was more effective than the 7-day CTT (RD = 0.25, 95%
      CI: 0.18/0.32), whereas no differences were observed between CTT and BQT given
      for 7 or 10 days. There were no statistical differences in side effects and
      compliance between both therapies (RD = 0.92, 95% CI: 0.76/1.12, and RD = -0.03,
      95% CI: -0.05/0.00, respectively). The effect of antibiotic resistance on
      eradication rates was reported in 4 of the 12 RCTs. Clarithromycin resistance
      significantly affected the efficacy of CTT (RD = 0.75, 95% CI: 0.63/0.87),
      whereas BQT efficacy was not affected by metronidazole resistance (RD = 0.09, 95%
      CI: -0.06/0.25). CONCLUSIONS: The 10-day BQT was more effective than the 7-day
      CTT as a first-line therapy for H. pylori infection, whereas BQT and CTT for 7 or
      10 days yielded similar eradication rates. Compliance and side effect rates were
      similar for both therapies. BQT overcomes clarithromycin resistance and its
      efficacy is not affected by metronidazole resistance.

PMID- 23880480
TI  - Dysfunctional parental styles perceived during childhood in outpatients with
      substance use disorders.
AB  - People who suffer from substance use disorders (SUDs) frequently report to have
      undergone childhood adversity that is often associated with father or mother
      dysfunction, or both. Yet that issue has been barely addressed in opiate
      dependent patients. Therefore we sought to evaluate parent-specific dysfunctional
      styles perceived during childhood in a clinical sample from an outpatient
      addiction treatment program using the Measure Of Parental Styles (MOPS)
      questionnaire. DSM-IV diagnoses of substance use disorders and history of suicide
      attempts, family structure and changes of caregiver during childhood were
      obtained from 159 consecutive outpatients, along with their perception of
      parental bonding with the MOPS, in which mother and father scores are separate.
      Mother neglect dimension was significantly correlated with an earlier age at
      onset of several substances' use, the number of prior hospitalizations and of
      lifetime suicide attempts. Most of these associations remained significant in
      multivariate models. This was the first assessment of a representative sample of
      outpatients with SUDs by the MOPS questionnaire. Given its excellent acceptance
      and its association with several key correlates of SUDs, it should be used to
      design specific interventions targeted at attachment and familial management as
      well as in research models on gene * environment interactions.

PMID- 23880481
TI  - Performance monitoring and executive control of attention in euthymic bipolar
      disorder: employing the CPT-AX paradigm.
AB  - Reduced cognitive test performance has been demonstrated in patients with bipolar
      disorder (BD), even when euthymic. Several studies have explored aspects of
      attention, including sustained attention, and reported patients show lower
      accuracy compared to controls. It is necessary to modify existing attentional
      paradigms to fully characterise such deficits. The present study sought to
      examine if there are changes in the profile of performance and error-types during
      a sustained attention task in BD. Twenty-two euthymic patients with DSM-IV
      diagnosed BD and 21 healthy controls were recruited. Participants completed a
      modified CPT-AX paradigm with a high proportion of target trials (70%) with cues
      and probes presented at continuous intervals. This modification increases the
      demands on response inhibition and permits the deconstruction of
      attentional/executive deficits previously described. Overall, BD patients showed
      significantly poorer target discriminability compared to controls. In block one
      (first quarter) of the task, patients showed no significant differences to
      controls, but by the final fourth block (last quarter) they made significantly
      fewer hits and more errors (both 'AX' misses and 'BX' false alarms). BD patients
      completed initial stages of the task similarly to controls, but as demands on the
      attentional system continued difficulties emerged, consistent with problems in
      context-maintenance. 

PMID- 23880482
TI  - Are neurological soft signs pre-existing markers in individuals with an at-risk
      mental state for psychosis?
AB  - Neurological soft signs (NSS) are more common in schizophrenic psychoses and in
      genetically high-risk individuals than in healthy controls. But nothing is known
      so far regarding individuals with a clinical at-risk mental state (ARMS). The
      goals of our study therefore were (a) to compare the NSS frequency in ARMS
      individuals to that of first-episode psychosis (FEP) patients and (b) to test
      whether NSS could predict the transition to psychosis. Neurological soft signs
      were assessed using a shortened version of the Neurological Evaluation Scale
      (NES). Fifty-three ARMS individuals (16 with later transition to psychosis=ARMS
      T, and 37 without transition=ARMS-NT) and 27 FEP patients were recruited through
      the Basel Early Detection Clinic FePsy. Of the FEP patients 37% showed NSS. We
      found no significant differences between FEP and ARMS-T patients or between ARMS
      NT and ARMS-T. Our findings of NSS being present already before transition to
      psychosis to the same extent as after transition provide further support to the
      neurodevelopmental hypothesis of schizophrenic psychoses. Furthermore, our
      findings might indicate that ARMS-NT individuals also suffer from some sort of
      neurodevelopmental abnormalities. 

PMID- 23880484
TI  - It is here. The DSM-5 has arrived.

PMID- 23880483
TI  - British Thoracic Society guideline on pulmonary rehabilitation in adults.

PMID- 23880485
TI  - Feedback which leads forward: where intervention begins.

PMID- 23880486
TI  - Copy number variation: what is it and what has it told us about child psychiatric
      disorders?

PMID- 23880487
TI  - The development of targeted neurobiological therapies in child and adolescent
      psychiatry.

PMID- 23880488
TI  - Trauma exposure and posttraumatic stress disorder in the lives of adolescents.

PMID- 23880489
TI  - Assessment and management of sleep problems in youths with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: To provide evidence- or consensus-based recommendations concerning the
      assessment and management of sleep problems in youths with attention
      deficit/hyperactivity disorder (ADHD). METHOD: PubMed, Ovid, EMBASE, and Web of
      Knowledge were searched through October 31, 2012. When no evidence was available,
      consensus of the authors was achieved. The evidence-level of the recommendations
      on the management of sleep disturbances was based on the Scottish Intercollegiate
      Guidelines Network (SIGN) system. RESULTS: A total of 139 original articles on
      sleep and childhood ADHD were retrieved, including 22 on treatment of sleep
      disturbances. This review focuses on behaviorally based insomnia, circadian
      rhythm disorder, sleep-disordered breathing, restless legs syndrome/periodic limb
      movement disorder, and sleep disturbances due to comorbid psychiatric disorders
      or ADHD medications. Healthy sleep practices are recommended as the foundation of
      management strategies. Behavioral interventions should be considered as first
      line treatment of insomnia, although further evidence from randomized controlled
      trials (RCTs) is needed to prove their efficacy in ADHD. Among pharmacological
      treatments, RCTs support the use of melatonin to reduce sleep-onset delay,
      whereas there is more limited evidence for other medications. CONCLUSION: Growing
      empirical evidence is informing assessment/management strategies of sleep
      problems in youths with ADHD. However, further RCTs are warranted to support
      current recommendations.

PMID- 23880490
TI  - Comparison of DSM-IV and DSM-5 factor structure models for toddlers with autism
      spectrum disorder.
AB  - OBJECTIVE: The present study examined the factor structure of autism symptoms in
      toddlers, to aid understanding of the phenotype during the developmental period
      that represents the earliest manifestations of autism symptoms. This endeavor is
      particularly timely, given changes in symptom structure from the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to the recently
      released Fifth Edition (DSM-5). METHOD: Factor structure was examined in a sample
      of toddlers between 12 and 30 months of age (mean = 20.37 months, SD = 3.32
      months) diagnosed with autism spectrum disorder (ASD) and recruited from
      community settings or referred for evaluation (N = 237). Confirmatory factor
      analyses were conducted comparing the relative fit of 4 distinct, previously
      proposed and validated models: DSM-5, DSM-IV, 1-factor, and an alternative 3
      factor model proposed by van Lang et al. RESULTS: Findings revealed that the 1
      factor model provided the poorest fit, followed by the DSM-IV model and the van
      Lang et al. model. The DSM-5 model provided the best fit to the data relative to
      other models and good absolute fit. Indicators for the confirmatory factor
      analyses, drawn from the Autism Diagnostic Observation Schedule-Toddler Module
      (ADOS-T), loaded strongly onto the DSM-5 Social Communication and Social
      Interaction factor and more variably onto the DSM-5 Restricted/Repetitive
      Language and Behavior factor. CONCLUSIONS: Results indicate that autism symptoms
      in toddlers, as measured by the ADOS-T, are separable and best deconstructed into
      the 2-factor DSM-5 structure, supporting the reorganization of symptoms in the
      DSM-5. Consistency of the present results in toddlers with previous studies in
      older children and adults suggests that the structure of autism symptoms may be
      similar throughout development.

PMID- 23880491
TI  - The association between autism spectrum disorder and psychotic experiences in the
      Avon longitudinal study of parents and children (ALSPAC) birth cohort.
AB  - OBJECTIVE: Studies report overlap between autism spectrum disorders and
      psychosis. This may indicate a relationship between the 2 disorders or an
      artificial overlap due to similarity of symptoms. The aim of this study was to
      investigate whether autism spectrum disorder and autistic traits predict
      psychotic experiences in early adolescence. METHOD: This study analyzes
      prospective data from a cohort. A dataset was analyzed of 5,359 cohort members
      who had provided data on autistic traits and/or a diagnosis of an autism spectrum
      disorder and psychotic experiences at age 12 years. RESULTS: A diagnosis of an
      autism spectrum disorder (odds ratio = 2.81, 95% confidence interval = 1.07, 7.34
      p = .035) and childhood autistic traits (odds ratio = 1.15, 95% confidence
      interval = 1.05, 1.26 p = .0018) were associated with psychotic experiences after
      adjustment for confounders. CONCLUSIONS: These findings suggest a shared
      neurodevelopmental origin for autism and psychosis.

PMID- 23880492
TI  - Trauma exposure and posttraumatic stress disorder in a national sample of
      adolescents.
AB  - OBJECTIVE: Although exposure to potentially traumatic experiences (PTEs) is
      common among youths in the United States, information on posttraumatic stress
      disorder (PTSD) risk associated with PTEs is limited. We estimate lifetime
      prevalence of exposure to PTEs and PTSD, PTE-specific risk of PTSD, and
      associations of sociodemographics and temporally prior DSM-IV disorders with PTE
      exposure, PTSD given exposure, and PTSD recovery among U.S. adolescents. METHOD:
      Data were drawn from 6,483 adolescent-parent pairs in the National Comorbidity
      Survey Replication Adolescent Supplement (NCS-A), a national survey of
      adolescents aged 13 through 17 years. Lifetime exposure to interpersonal
      violence, accidents/injuries, network/witnessing, and other PTEs was assessed
      along with DSM-IV PTSD and other distress, fear, behavior, and substance
      disorders. RESULTS: A majority (61.8%) of adolescents experienced a lifetime PTE.
      Lifetime prevalence of DSM-IV PTSD was 4.7% and was significantly higher among
      females (7.3%) than among males (2.2%). Exposure to PTEs, particularly
      interpersonal violence, was highest among adolescents not living with both
      biological parents and with pre-existing behavior disorders. Conditional
      probability of PTSD was highest for PTEs involving interpersonal violence.
      Predictors of PTSD among PTE-exposed adolescents included female gender, prior
      PTE exposure, and pre-existing fear and distress disorders. One-third (33.0%) of
      adolescents with lifetime PTSD continued to meet criteria within 30 days of
      interview. Poverty, U.S. nativity, bipolar disorder, and PTE exposure occurring
      after the focal trauma predicted nonrecovery. CONCLUSIONS: Interventions designed
      to prevent PTSD in PTE-exposed youths should be targeted at victims of
      interpersonal violence with pre-existing fear and distress disorders, whereas
      interventions designed to reduce PTSD chronicity should attempt to prevent
      secondary PTE exposure.

PMID- 23880493
TI  - Irritable mood as a symptom of depression in youth: prevalence, developmental,
      and clinical correlates in the Great Smoky Mountains Study.
AB  - OBJECTIVE: DSM-IV grants episodic irritability an equal status to low mood as a
      cardinal criterion for the diagnosis of depression in youth, yet not in adults;
      however, evidence for irritability as a major criterion of depression in youth is
      lacking. This article examines the prevalence, developmental characteristics,
      associations with psychopathology, and longitudinal stability of irritable mood
      in childhood and adolescent depression. METHOD: Data from the prospective
      population-based Great Smoky Mountains Study (N = 1,420) were used. We divided
      observations on 9- to 16-year-olds who met criteria for a diagnosis of depression
      into 3 groups: those with depressed mood and no irritability, those with
      irritability and no depressed mood, and those with both depressed and irritable
      mood. We compared these groups using robust regression models on adolescent
      characteristics and early adult (ages 19-21 years) depression outcomes. RESULTS:
      Depressed mood was the most common cardinal mood in youth meeting criteria for
      depression (58.7%), followed by the co-occurrence of depressed and irritable mood
      (35.6%); irritable mood alone was rare (5.7%). Youth with depressed and irritable
      mood were similar in age and developmental stage to those with depression, but
      had significantly higher rates of disruptive disorders. The co-occurrence of
      depressed and irritable mood was associated with higher risk for comorbid conduct
      disorder in girls (gender-by-group interaction, F1,132 = 4.66, p = .03).
      CONCLUSIONS: Our study findings do not support the use of irritability as a
      cardinal mood criterion for depression. However, the occurrence of irritability
      in youth depression is associated with increased risk of disruptive behaviors,
      especially in girls.

PMID- 23880494
TI  - The dysregulation profile in young children: empirically defined classes in the
      Generation R study.
AB  - OBJECTIVE: Children with co-occurring internalizing and externalizing problems
      have higher levels of impairment and worse outcomes later in life, but it is
      unclear whether these children can be distinguished validly from children who
      have problems in a single domain. We used a person-centered statistical approach
      to examine whether a group of children with co-occurring internalizing and
      externalizing problems can be identified in a general-population sample of young
      children. METHOD: This study included a population-based sample of 6,131
      children, aged 5 through 7 years. Mothers (92.6%) reported emotional and
      behavioral problems using the Child Behavior Checklist/1.5-5 (CBCL). A latent
      profile analysis was performed on the CBCL syndrome scales. Identified classes
      were compared on early socioeconomic and parental risk factors using multinomial
      logistic regression. RESULTS: We identified 4 classes, as follows: a class
      scoring high on all internalizing and externalizing scales (1.8%); a class with
      internalizing problems (5.3%); a class with externalizing problems and emotional
      reactivity (7.3%); and a class without problems (85.6%). The first class, with co
      occurring problems, was associated with higher levels of maternal and paternal
      affective symptoms and hostility than the other 3 classes. CONCLUSIONS: The class
      with co-occurring internalizing and externalizing problems appears to be highly
      similar to the CBCL Dysregulation Profile described in older children. This
      empirically based dysregulation profile offers a promise to the study of the
      development of poor self-regulation.

PMID- 23880495
TI  - Family intervention for adolescents with suicidal behavior: a randomized
      controlled trial and mediation analysis.
AB  - OBJECTIVE: Family processes are a risk factor for suicide but few studies target
      this domain. We evaluated the effectiveness of a family intervention, the
      Resourceful Adolescent Parent Program (RAP-P) in reducing adolescent suicidal
      behavior and associated psychiatric symptoms. METHOD: A preliminary randomized
      controlled trial compared RAP-P plus Routine Care (RC) to RC only, in an
      outpatient psychiatric clinic for N = 48 suicidal adolescents and their parents.
      Key outcome measures of adolescent suicidality, psychiatric disability, and
      family functioning were completed at pre-treatment, 3-month, and 6-month follow
      up. RESULTS: RAP-P was associated with high recruitment and retention, greater
      improvement in family functioning, and greater reductions in adolescents'
      suicidal behavior and psychiatric disability, compared to RC alone. Benefits were
      maintained at follow-up with a strong overall effect size. Changes in
      adolescent's suicidality were largely mediated by changes in family functioning.
      CONCLUSION: The study provides preliminary evidence for the use of family-focused
      treatments for adolescent suicidal behavior in outpatient settings. Clinical
      trial registration information-Family intervention for adolescents with suicidal
      behaviour: A randomized controlled trial and mediation analysis;
      http://anzctr.org/; ACTRN12613000668707.

PMID- 23880497
TI  - Further thoughts about "a child psychiatrist in the house".

PMID- 23880496
TI  - Psychodynamic psychotherapy for children and adolescents: a meta-analysis of
      short-term psychodynamic models.
AB  - OBJECTIVE: Psychodynamically based brief psychotherapy is frequently used in
      clinical practice for a range of common mental disorders in children and
      adolescents. To our knowledge, there have been no meta-analyses to evaluate the
      effectiveness of these therapies. METHOD: After a broad search, we meta-analyzed
      controlled outcome studies of short-term psychodynamic psychotherapies (STPP, 40
      or fewer sessions). We also performed sensitivity analyses and evaluated the risk
      of bias in this body of studies. RESULTS: We found 11 studies with a total of 655
      patients covering a broad range of conditions including depression, anxiety
      disorders, anorexia nervosa, and borderline personality disorder. STPP did not
      separate from what were mostly robust treatment comparators, but there were some
      subgroup differences. Robust (g = 1.07, 95% CI = 0.80-1.34) within group effect
      sizes were observed suggesting the treatment may be effective. These effects
      increased in follow up compared to post treatment (overall, g = 0.24, 95% CI =
      0.00-0.48), suggesting a tendency toward increased gains. Heterogeneity was high
      across most analyses, suggesting that these data need be interpreted with
      caution. CONCLUSION: This review suggests that STPP may be effective in children
      and adolescents across a range of common mental disorders.

PMID- 23880498
TI  - Drs. Keller and Sarvet reply.

PMID- 23880501
TI  - Lipoxin A4 ameliorates cerebral ischaemia/reperfusion injury through upregulation
      of nuclear factor erythroid 2-related factor 2.
AB  - OBJECTIVES: Lipoxin A4 (LXA4) is a potent anti-inflammatory mediator that exerts
      a neuroprotective effect following cerebral ischaemia/reperfusion (I/R) injury.
      However, little is known about the underlying mechanisms. Upregulation of nuclear
      factor erythroid 2-related factor 2 (Nrf2) is generally considered to reduce
      cerebral I/R injury. Nuclear factor erythroid 2-related factor 2 can induce haeme
      oxygenase-1 (HO-1) and glutathione (GSH) expression to combat increased oxidative
      stress. The present study aimed to investigate the effects of Nrf2 signalling on
      LXA4-mediated neuroprotection. METHODS: Adult male Sprague Dawley rats were
      subjected to 2-hour middle cerebral artery occlusion followed by 24-hour
      reperfusion. Rats were randomly divided into four groups: Sham, I/R, LXA4, and
      LXA4+butoxycarbonyl-Phe-Leu-Phe-Leu-Phe (Boc2) (all n = 24). Brain infarction was
      detected by 2,3,5-triphenyltetrazolium chloride staining. After 24 hours of
      reperfusion, Nrf2, HO-1, and p62 expression levels were determined by western
      blot, and GSH synthesis was assessed. RESULTS: Lipoxin A4 effectively reduced
      infarct volumes and improved neurological scores. These effects were partially
      blocked by Boc2, a specific antagonist of the LXA4 receptor (ALXR). Lipoxin A4
      induced Nrf2 expression and its nuclear translocation, as well as HO-1 expression
      and GSH synthesis; Boc2 did not block these effects. The excess p62 accumulation
      induced by LXA4 might be closely related to Nrf2 activation. DISCUSSION: Overall,
      our data suggest that Nrf2 upregulation is involved in the neuroprotective
      effects of LXA4 and may be ALXR independent.

PMID- 23880500
TI  - Is neuroenhancement by noninvasive brain stimulation a net zero-sum proposition?
AB  - In the past several years, the number of studies investigating enhancement of
      cognitive functions through noninvasive brain stimulation (NBS) has increased
      considerably. NBS techniques, such as transcranial magnetic stimulation and
      transcranial current stimulation, seem capable of enhancing cognitive functions
      in patients and in healthy humans, particularly when combined with other
      interventions, including pharmacologic, behavioral and cognitive therapies. The
      "net zero-sum model", based on the assumption that brain resources are subjected
      to the physical principle of conservation of energy, is one of the theoretical
      frameworks proposed to account for such enhancement of function and its potential
      cost. We argue that to guide future neuroenhancement studies, the net-zero sum
      concept is helpful, but only if its limits are tightly defined. 

PMID- 23880503
TI  - Group C betacoronavirus in bat guano fertilizer, Thailand.

PMID- 23880502
TI  - Chimerism of bone marrow mesenchymal stem/stromal cells in allogeneic
      hematopoietic cell transplantation: is it clinically relevant?
AB  - Multipotent mesenchymal stem/stromal cells (MSCs) have been extensively used as a
      transplantable cell source for regenerative medicine and immunomodulatory
      therapy. Specifically in allogeneic hematopoietic stem cell transplantation
      (HSCT), co-transplantation or post-transplant infusion of MSCs derived from bone
      marrow (BM) of non-self donors has been implicated in accelerating hematopoietic
      recovery, ameliorating graft-vs.-host disease, and promoting tissue regeneration.
      However, irrespective of the use of MSC co-administration, post-transplant
      chimerism of BM-derived MSCs after allogeneic HSCT has been reported to remain of
      host origin, suggesting that the infused donor MSCs are immunologically rejected
      or not capable of long-term engraftment in the host microenvironment. Also,
      hematopoietic cell allografts currently used for HSCT do not seem to contain
      sufficient amount of MSCs or their precursors to reconstitute host BM
      microenvironment. Since the toxic conditioning employed in allo-HSCT may impair
      the function of host MSCs to maintain hematopoietic/regenerative stem cell niches
      and to provide a local immunomodulatory milieu, we propose that new directions
      for enhancing immunohematopoietic reconstitution and tissue repair after
      allogeneic HSCT include the development of strategies to support functional
      replenishment of residual host MSCs or to support more efficient engraftment of
      infused donor MSCs. Future areas of research should include in vivo tracking of
      infused MSCs and detection of their microchimeric presence in extra-marrow sites
      as well as in BM. 

PMID- 23880504
TI  - Frequency, virulence genes and antimicrobial resistance of Listeria spp. isolated
      from bovine clinical mastitis.
AB  - The aims of this study were to determine the prevalence, characteristics and
      antimicrobial resistance of Listeria spp. isolated from bovine clinical mastitis
      in Iran. Listeria spp. were detected in 21/207 bovine mastitic milk samples from
      dairy farms in Iran, comprising L. monocytogenes (n=17), L. innocua (n=3) and L.
      ivanovii (n=1). L. monocytogenes isolates were grouped into serogroups '4b, 4d,
      4e', '1/2a, 3a', '1/2b, 3b, 7' and '1/2c, 3c'; all harboured inlA, inlC and inlJ
      virulence genes. Listeria spp. were most frequently resistant to penicillin G
      (14/21 isolates, 66.7%) and tetracyclines (11/21 isolates, 52.4%). 

PMID- 23880505
TI  - Encapsulated cell therapy for neurodegenerative diseases: from promise to
      product.
AB  - Delivering therapeutic molecules, including trophic factor proteins, across the
      blood brain barrier to the brain parenchyma to treat chronic neurodegenerative
      diseases remains one of the great challenges in biology. To be effective,
      delivery needs to occur in a long-term and stable manner at sufficient quantities
      directly to the target region in a manner that is selective but yet covers enough
      of the target site to be efficacious. One promising approach uses cellular
      implants that produce and deliver therapeutic molecules directly to the brain
      region of interest. Implanted cells can be precisely positioned into the desired
      region and can be protected from host immunological attack by encapsulating them
      and by surrounding them within an immunoisolatory, semipermeable capsule. In this
      approach, cells are enclosed within a semiporous capsule with a perm selective
      membrane barrier that admits oxygen and required nutrients and releases bioactive
      cell secretions while restricting passage of larger cytotoxic agents from the
      host immune defense system. Recent advances in human cell line development have
      increased the levels of secreted therapeutic molecules from encapsulated cells,
      and membrane extrusion techniques have led to the first ever clinical
      demonstrations of long-term survival and function of encapsulated cells in the
      brain parenchyma. As such, cell encapsulation is capable of providing a targeted,
      continuous, de novo synthesized source of very high levels of therapeutic
      molecules that can be distributed over significant portions of the brain. 

PMID- 23880506
TI  - Role of integrated cancer nanomedicine in overcoming drug resistance.
AB  - Cancer remains a major killer of mankind. Failure of conventional chemotherapy
      has resulted in recurrence and development of virulent multi drug resistant (MDR)
      phenotypes adding to the complexity and diversity of this deadly disease. Apart
      from displaying classical physiological abnormalities and aberrant blood flow
      behavior, MDR cancers exhibit several distinctive features such as higher
      apoptotic threshold, aerobic glycolysis, regions of hypoxia, and elevated
      activity of drug-efflux transporters. MDR transporters play a pivotal role in
      protecting the cancer stem cells (CSCs) from chemotherapy. It is speculated that
      CSCs are instrumental in reviving tumors after the chemo and radiotherapy. In
      this regard, multifunctional nanoparticles that can integrate various key
      components such as drugs, genes, imaging agents and targeting ligands using
      unique delivery platforms would be more efficient in treating MDR cancers. This
      review presents some of the important principles involved in development of MDR
      and novel methods of treating cancers using multifunctional-targeted
      nanoparticles. Illustrative examples of nanoparticles engineered for drug/gene
      combination delivery and stimuli responsive nanoparticle systems for cancer
      therapy are also discussed.

PMID- 23880507
TI  - UV-Vis as quantification tool for solubilized lignin following a single-shot
      steam process.
AB  - In this short communication, UV/Vis was used as an analytical tool for the
      quantification of lignin concentrations in aqueous mediums. A significant
      correlation was determined between absorbance and concentration of lignin in
      solution. For this study, lignin was produced from different types of biomasses
      (willow, aspen, softwood, canary grass and hemp) using steam processes.
      Quantification was performed at 212, 225, 237, 270, 280 and 287 nm. UV-Vis
      quantification of lignin was found suitable for different types of biomass making
      this a timesaving analytical system that could lead to uses as Process Analytical
      Tool (PAT) in biorefineries utilizing steam processes or comparable approaches.

PMID- 23880508
TI  - Radiation-induced epigenetic DNA methylation modification of radiation-response
      pathways.
AB  - DNA methylation can regulate gene expression and has been shown to modulate
      cancer cell biology and chemotherapy resistance. Therapeutic radiation results in
      a biological response to counter the subsequent DNA damage and genomic stress in
      order to avoid cell death. In this study, we analyzed DNA methylation changes
      at>450,000 loci to determine a potential epigenetic response to ionizing
      radiation in MDA-MB-231 cells. Cells were irradiated at 2 and 6 Gy and analyzed
      at 7 time points from 1-72 h. Significantly differentially methylated genes were
      enriched in gene ontology categories relating to cell cycle, DNA repair, and
      apoptosis pathways. The degree of differential methylation of these pathways
      varied with radiation dose and time post-irradiation in a manner consistent with
      classical biological responses to radiation. A cell cycle arrest was observed 24
      h post-irradiation and DNA damage, as measured by gammaH2AX, resolved at 24 h. In
      addition, cells showed low levels of apoptosis 2-48 h post-6 Gy and cellular
      senescence became significant at 72 h post-irradiation. These DNA methylation
      changes suggest an epigenetic role in the cellular response to radiation. 

PMID- 23880509
TI  - The relationship between conduct symptoms and the recognition of emotions in non
      clinical adolescents.
AB  - BACKGROUND: In adult individuals with antisocial personality disorder, impairment
      in the recognition of fear seems established. In adolescents with conduct
      disorder (antecedent of antisocial personality disorder), only sporadic data were
      assessed, but literature data indicate alterations in the recognition of
      emotions. The aim of the present study was to assess the relationship between
      emotion recognition and conduct symptoms in non-clinical adolescents. METHODS: 53
      adolescents participated in the study (13-16 years, boys, n=29, age 14.7+/-0.2
      years; girls, n=24, age=14.7+/-0.2 years) after informed consent. The parent
      version of the Strengths and Difficulties Questionnaire was used to assess
      behavioral problems. The recognition of six basic emotions was established by the
      "Facial expressions of emotion-stimuli and tests", while Raven IQ measures were
      also performed. RESULTS: Compared to boys, girls showed significantly better
      performance in the recognition of disgust (p<0.035), while no significant
      difference occurred in the recognition of other emotions. In boys, Conduct
      Problems score was inversely correlated with the recognition of fear (Spearman R=
      0.40, p<0.031) and overall emotion recognition (Spearman R=-0.44, p<0.015), while
      similar correlation was not present in girls. CONCLUSIONS: The relationship
      between the recognition of emotions and conduct problems might indicate an
      important mechanism in the development of antisocial behavior.

PMID- 23880510
TI  - [Which way ahead for psychiatry? Identity, competence and cooperation--challenges
      of the 21st century].
AB  - In the past decades some disadvantageous changes have been occurred in almost
      each field of medicine, especially neurology and psychiatry. Medical students and
      young doctors are less and less able to utilize their neurological knowledge in
      the everyday clinical practice and the number of doctors specialized in
      neurosciences is decreasing. Recent problems of psychiatry originate from special
      development, controversial process of detachment, particular societal and
      cultural roots, differences from medical model, and problems of identity, self
      determination and competence, which may cause many difficulties in clinical
      practice. The author - near the review of the theoretical background - mentions
      several practical topics as well, for example: the difficulties of diagnosing,
      and classification of mental disorders, the diagnostic and treating problems
      being in the background of psychopathological symptoms. In the article it is
      emphasized that the present situation results in several serious problems for the
      psychiatrists like emotional overburden, somatic and mental disorders and
      burnout, moreover psychiatry became one of the least popular medical professions,
      which causes huge difficulties in the aftergrowth. Furthermore the author
      emphasises, that this profession has to actualize the humanistic view in clinical
      practice based on the holistic bio-psycho-socio-spiritual approach. The
      (neuro)scientific and consultative psychiatric viewpoints, the constructive intra
      and interdisciplinary communication, the more effective value-based advocacy and
      the modern, evidence-based, interactive and personal education together have a
      key role in the solution of the above mentioned problems.

PMID- 23880511
TI  - [Problematic online gaming. A review of the literature].
AB  - In parallel with the increasing popularity of online games, researchers have
      reported an increasing number of problematic users. For this reason there is a
      growing amount of literature analyzing the effects of online games. The present
      review described the evolution of online games as well as their types and
      specific characteristics of these types. This review examines (i) the question of
      definition, (ii) symptoms of problematic use, (iii) the measurement instruments
      (iv) prevalence data, (v) issues of etiology, (vi) the results of comorbidity,
      and (vii) the main trends and results in the area of prevention and treatment.

PMID- 23880512
TI  - [Major psychiatric disorders and filicide: a descriptive analysis of filicides
      perpetrated by women with psychotic mental illness].
AB  - INTRODUCTION: This study aims to reflect on the connection between maternal
      filicide and major psychiatric disorders based on international literature, and
      analysis of filicides perpetrated by women and ending with compulsory medical
      treatment based on a not guilty by reason of insanity verdict. METHOD: For the
      purpose of the analysis we collected cases back to 1993 from the archives of the
      Forensic Observation and Psychiatric Institution (IMEI), when a female
      perpetrator committed homicide against her blood-related offspring, after which
      she spent her compulsory medical treatment in the Institution. We had 14 cases
      which were only descriptively analysed due to the low number of cases. We
      collected data through overview of the documentation of the patients. We focused
      on several factors: demographic characteristics of the victims, characteristics
      of the homicidal act, demographic and psychiatric characteristics of the
      perpetrators. RESULTS: Most importantly, our results show interesting findings in
      the field of gender distribution of the victims. In relation to suicide risk, our
      results concur with previous findings pointing out its strong connection with
      filicide. Furthermore, our findings point out the relevance of schizoaffective
      disorder, as it was the most frequent diagnosis in our cases. CONCLUSION: We make
      our conclusions primarily in regard of prevention, we emphasise the strongest
      risk factors according to the results, which can draw the clinical practitioner's
      attention to the danger of filicide.

PMID- 23880513
TI  - [Tones and being tuned. Suggestions for the common origins of music therapy and
      hypnotherapy].
AB  - Sound vibrations are viewed to play an important role in embryonic development.
      Before the cochlea evolves, the haptic and mechanic skin-receptors detect the
      amniotic fluid's pressure-waves produced by sounds in uterus. Touching and
      hearing are seen as primordial and the most relevant stimuli both of mother-fetus
      attunement and development of fetal nervous system. Man is attuned to
      environmental stimuli, mainly to human speaking since the embryonic period.
      Attunement is secured by energy zones (chakras) circling around body. It is
      considered to be base of our music capacity. Origin of hypnotic susceptibility is
      viewed as being in embryonic period as well. Movements, experiences supposed,
      bonding and communication patterns of both of fetus and hypnotized person are
      suggested to show similarities. Prenatal audio-somatosensory stimulating program
      facilitates newborn babies' cognitive, emotional and bonding capacities. As a
      matter of fact, by virtue of regressive fetus-like experiences, hypnotherapy
      contributes to the restart of personality development halted by trauma.

PMID- 23880514
TI  - [Validation of the Hungarian version of the Strengths and Difficulties
      Questionnaire in an adolescent clinical population].
AB  - INTRODUCTION: The short Strengths and Difficulties Questionnaire (SDQ) available
      in parent, teacher and self-report versions, is used world-wide for assessing and
      screening childhood behavior and mental problems, as part of clinical
      assessments, therapy outcome evaluations, and research tool. The aim of the
      present study was to extend the use of Hungarian version to a clinical sample, to
      examine the clinical cut-off values suggested previously on the basis of a
      normative sample, and to test the questionnaire's sensitivity in differentiating
      between different psychiatric disorders. METHOD: The parent and self-report
      versions of the five scale SDQ-Magy questionnaire was filled in by 716 parents
      and their children admitted to Vadaskert Child Psychiatry and Outpatient Clinic.
      Clinical (ICD) diagnoses were determined during psychiatric examination. RESULTS:
      With a few exceptions, internal consistencies of the scales were satisfactory
      (0,55-0,79), the parent version showing greater reliability compared to the self
      report version. Children's age, gender, and parents' level of education had some
      effect on the scale scores. The questionnaire's Total problem and symptom scale
      scores were very effective in discriminating between the control and the clinical
      sample. In the clinical sample, parents rated their children's behavior and
      mental problems as more severe. Profiles of scale scores distinguished the wider
      internalizing, externalizing, and co-morbid diagnostic categories, as well as the
      eight specific diagnoses. Based on the normal-abnormal cut-off values proposed
      earlier (Turi et al., 2011), the great majority of clinical cases were screened
      by the questionnaire. CONCLUSIONS: The Hungarian version of the SDQ proved
      applicable in a clinical sample. Psychometric properties, variances due to age,
      gender and informant were consistent with international experiences. SDQ profiles
      related to clinical diagnoses and their difference from the control group show
      the sensitivity and discriminative power of the questionnaire, while the
      screening ability based on clinical cut-offs also supports the clinical use of
      the questionnaire.

PMID- 23880515
TI  - [Pedophilia].
AB  - This article deals with the incidence, diagnosis and treatment of pedophilia as a
      conceptualized mental disorder. Pedophilia is a category of sexual deviation
      characterized by a sexual interest toward children under 13 years according to
      DSM-IV-TR or children under 14 years as determined by the law. Pedophilia is a
      distinguished form of child sexual abuse as a legal category. Today pedophilia
      patients are stigmatized and excluded from society not only in general, but also
      in prisons and forensic units. However, the phenomenon of pedophilia originates
      from the disorder of emotional, cognitive, sexual development as well as some
      social factors have also a significant role in this area, especially virtual
      social networks and the media. The combination of miscellaneous factors makes the
      social reintegration of patients in treatment very difficult and results in a
      high risk for relapse. The complexity of this topic can also be demonstrated by
      the high frequency of mental disorders among the victims.

PMID- 23880516
TI  - [Observations of MDPV users: a prospective-retrospective study].
AB  - INTRODUCTION: The spreading of "designer drugs" resulted in the appearance of
      "similar yet different" substances, the chemical structure of which are modified
      so regularly, which makes their research very difficult. We came across one of
      these substances, MDPV, while on night duty before it was mentioned in research
      papers. Our own research explores the changes in drug consumption patterns,
      especially in MDPV consumption patterns in the past few years, and gives a
      description of psychiatric and associated symptoms. METHOD: We compared cases of
      patients admitted to our ward between Jan 1., 2010 and November 30., 2012 with
      symptoms of drug consumption and its complications (BNO F15.00-F15.90, F19.00
      F19.90). We examined symptoms that required inpatient care at the psychiatry
      ward. RESULTS: While in 2010 we treated only 3 MDPV users on 6 occasions, 4
      Mephedrone users on 6 occasions, and 9 patients using other substances (Speed,
      Cannabis) on 10 occasions at our ward, in 2011 there were no Mephedrone-related
      hospitalizations and only 9 patients using other substances (Cannabis, Synthetic
      Cannabinoid, 5-MeO-AMT, Glue, Metamizole, Ketamine) were treated on 13 occasions.
      Between Jan 1. 2011. and Nov 30.2012 there were 40 recorded cases related to MDPV
      use in the period: forty people were registered on 87 occasions. Nine people
      receive impatient care after observation on 10 occasions. In all these cases
      psychotic symptoms were recorded. CONCLUSION: The constant development of
      designer drugs requires better administration of the individual cases, symptoms
      and forms of treatments. Informing doctors about these details also seems
      necessary. We have found that the behaviours of drug users show a positive
      correspondence with changing legal environments, which calls for a more sensible
      drug-related policy.

PMID- 23880517
TI  - Endocannabinoid signaling in cancer: a rather complex puzzle.

PMID- 23880518
TI  - E2f6-mediated repression of the meiotic Stag3 and Smc1beta genes during early
      embryonic development requires Ezh2 and not the de novo methyltransferase Dnmt3b.
AB  - The E2f6 transcriptional repressor is an E2F-family member essential for the
      silencing of a group of meiosis-specific genes in somatic tissues. Although E2f6
      has been shown to associate with both polycomb repressive complexes (PRC) and the
      methyltransferase Dnmt3b, the cross-talk between these repressive machineries
      during E2f6-mediated gene silencing has not been clearly demonstrated yet. In
      particular, it remains largely undetermined when and how E2f6 establishes
      repression of meiotic genes during embryonic development. We demonstrate here
      that the inactivation of a group of E2f6 targeted genes, including Stag3 and
      Smc1beta, first occurs at the transition from mouse embryonic stem cells (ESCs)
      to epiblast stem cells (EpiSCs), which represent pre- and post-implantation
      stages, respectively. This process was accompanied by de novo methylation of
      their promoters. Of interest, despite a clear difference in DNA methylation
      status, E2f6 was similarly bound to the proximal promoter regions both in ESCs
      and EpiSCs. Neither E2f6 nor Dnmt3b overexpression in ESCs decreased meiotic gene
      expression or increased DNA methylation, indicating that additional factors are
      required for E2f6-mediated repression during the transition. When the SET domain
      of Ezh2, a core subunit of the PRC2 complex, was deleted, however, repression of
      Stag3 and Smc1beta during embryoid body differentiation was largely impaired,
      indicating that the event required the enzymatic activity of Ezh2. In addition,
      repression of Stag3 and Smc1beta occurred in the absence of Dnmt3b. The data
      presented here suggest a primary role of PRC2 in E2f6-mediated gene silencing of
      the meiotic genes. 

PMID- 23880520
TI  - Self-assembly of three-dimensional interconnected graphene-based aerogels and its
      application in supercapacitors.
AB  - Homogeneously distributed self-assembling hybrid graphene-based aerogels with 3D
      interconnected pores, employing three types of carbohydrates (glucose, beta
      cyclodextrin, and chitosan), have been fabricated by a simple hydrothermal route.
      Using three types of carbohydrates as morphology oriented agents and reductants
      can effectively tailor the microstructures, physical properties, and
      electrochemical performances of the products. The effects of different
      carbohydrates on graphene oxide reduction to form graphene-based aerogels with
      different microcosmic morphologies and physical properties were also systemically
      discussed. The electrochemical behaviors of all graphene-based aerogel samples
      showed remarkably strong and stable performances, which indicated that all the 3D
      interpenetrating microstructure graphene-based aerogel samples with well
      developed porous nanostructures and interconnected conductive networks could
      provide fast ionic channels for electrochemical energy storage. These results
      demonstrate that this strategy would offer an easy and effective way to fabricate
      graphene-based materials. 

PMID- 23880519
TI  - Placental HTR2A methylation is associated with infant neurobehavioral outcomes.
AB  - The serotonin receptor, HTR2A, exhibits placental expression and function and can
      be controlled through DNA methylation. The relationship between methylation of
      HTR2A in the placenta and neurodevelopmental outcomes, evaluated using the NICU
      Network Neurobehavioral Scales (NNNS), was assessed in newborn infants (n = 444).
      HTR2A methylation was significantly higher in males and marginally higher in
      infants whose mothers reported tobacco use during pregnancy. Controlling for
      confounding variables, HTR2A methylation was negatively associated with infant
      quality of movement (p = 0.05) and positively associated with infant attention (p
      = 0.0001). These results suggest that methylation of the HTR2A gene can be
      biologically and environmentally modulated and is associated with key measures of
      neurodevelopment. 

PMID- 23880521
TI  - Electrophoretic nanotechnology of graphene-carbon nanotube and graphene
      polypyrrole nanofiber composites for electrochemical supercapacitors.
AB  - Thin films of multiwalled carbon nanotubes (MWCNT), graphene and polypyrrole
      (PPy) nanofibers were prepared by cathodic electrophoretic deposition (EPD) from
      aqueous suspensions, containing safranin (SAF) as a new dispersant. The results
      of Fourier transform infrared spectroscopy, UV-Vis spectroscopy studies and
      sedimentation tests, coupled with deposition yield and electron microscopy data
      showed that SAF adsorbed on MWCNT, graphene and PPy, provided their dispersion
      and charging in the suspensions and allowed efficient EPD. The deposition yield
      can be controlled by the variation of SAF concentration in the suspensions and
      deposition time. The use of SAF as a co-dispersant for MWCNT, graphene and PPy,
      allowed controlled EPD of composite graphene-MWCNT and graphene-PPy films. The
      proposed approach for the deposition of PPy paves the way for EPD of neutral
      polymers using organic dyes as dispersing and charging agents. The composite
      films were investigated for application in electrochemical supercapacitors (ES).
      The graphene-MWCNT and graphene-PPy films showed significant increase in
      capacitance, decrease in resistance and increase in capacitance retention at high
      charge-discharge rates compared to the films of individual components. The
      analysis of electrochemical testing results and electron microscopy data provided
      an insight into the influence of composite microstructure on electrochemical
      performance. The composites, prepared by EPD are promising materials for
      electrodes of ES. 

PMID- 23880522
TI  - Process of in situ forming well-aligned zinc oxide nanorod arrays on wood
      substrate using a two-step bottom-up method.
AB  - A good nanocrystal covering layer on wood can serve as a protective coating and
      present some new surface properties. In this study, well-aligned ZnO nanorods
      (NRs) arrays were successfully grown on wood surface through a two-step bottom-up
      growth process. The process involved pre-sow seeds and subsequently their growing
      into NRs under hydrothermal environment. The interface incorporation between wood
      and ZnO colloid particles in the precursor solution during the seeding process
      was analyzed and demonstrated through a schematic. The growth process of forming
      well-aligned ZnO NRs was analyzed by field-emission scanning electron microscopy
      and X-ray diffraction, which showed that the NRs elongated with increased
      reaction time. The effects of ZnO crystal form and capping agent on the growth
      process were studied through different viewpoints. 

PMID- 23880523
TI  - A Monte-Carlo based model of the AX-PET demonstrator and its experimental
      validation.
AB  - AX-PET is a novel PET detector based on axially oriented crystals and orthogonal
      wavelength shifter (WLS) strips, both individually read out by silicon photo
      multipliers. Its design decouples sensitivity and spatial resolution, by reducing
      the parallax error due to the layered arrangement of the crystals. Additionally
      the granularity of AX-PET enhances the capability to track photons within the
      detector yielding a large fraction of inter-crystal scatter events. These events,
      if properly processed, can be included in the reconstruction stage further
      increasing the sensitivity. Its unique features require dedicated Monte-Carlo
      simulations, enabling the development of the device, interpreting data and
      allowing the development of reconstruction codes. At the same time the non
      conventional design of AX-PET poses several challenges to the simulation and
      modeling tasks, mostly related to the light transport and distribution within the
      crystals and WLS strips, as well as the electronics readout. In this work we
      present a hybrid simulation tool based on an analytical model and a Monte-Carlo
      based description of the AX-PET demonstrator. It was extensively validated
      against experimental data, providing excellent agreement. 

PMID- 23880524
TI  - Outcomes of secondary self-expandable metal stents versus surgery after delayed
      initial palliative stent failure in malignant colorectal obstruction.
AB  - BACKGROUND/AIMS: When re-intervention is required due to an occluded first
      colorectal self-expanding metal stent for malignant colorectal obstruction,
      serious controversies exist regarding whether to use endoscopic re-stenting or
      surgery. To compare the clinical outcomes in patients who underwent stent re
      insertion versus palliative surgery as a second intervention. METHODS: A total of
      115 patients who received either self-expandable metal stent (SEMS) insertion or
      palliative surgery for treatment of a second occurrence of malignant colorectal
      obstruction after the first SEMS placement were retrospectively studied between
      July 2005 and December 2009. RESULTS: The median overall survival (8.2 vs. 15.5
      months) and progression-free survival (4.0 vs. 2.7 months) were not significantly
      different between the stent and surgery groups (p = 0.895 and 0.650,
      respectively). The median lumen patency in the stent group was 3.4 months and
      that in the surgery group was 7.9 months (p = 0.003). The immediate complication
      rate after second stent insertion was 13.9% and late complication rate was
      observed in 12 of 79 (15.2%) patients. There was no mortality related to the SEMS
      procedure. The complication and mortality rates associated with palliative
      surgery were 3.5% (2/57) and 12.3% (7/57), respectively. CONCLUSIONS: Although
      there is no significant difference in the overall survival between stenting and
      surgery, a secondary stent insertion had a lower mortality rate despite a shorter
      duration of temporary colorectal decompression compared to that of palliative
      surgery.

PMID- 23880525
TI  - Emotional communication in medical consultations with native and non-native
      patients applying two different methodological approaches.
AB  - OBJECTIVE: To explore the potential agreement between two different methods to
      investigate emotional communication of native and non-native patients in medical
      consultations. METHODS: The data consisted of 12 videotaped hospital
      consultations with six native and six non-native patients. The consultations were
      coded according to coding rules of the Verona Coding definitions of Emotional
      Sequences (VR-CoDES) and afterwards analyzed by discourse analysis (DA) by two co
      workers who were blind to the results from VR-CoDES. RESULTS: The agreement
      between VR-CoDES and DA was high in consultations with many cues and concerns,
      both with native and non-native patients. In consultations with no (or one cue)
      according to VR-CoDES criteria the DA still indicated the presence of emotionally
      salient expressions and themes. CONCLUSION: In some consultations cues to
      underlying emotions are communicated so vaguely or veiled by language barriers
      that standard VR-CoDES coding may miss subtle cues. Many of these sub-threshold
      cues could potentially be coded as cues according to VR-CoDES main coding
      categories, if criteria for coding vague or ambiguous cues had been better
      specified. PRACTICE IMPLICATIONS: Combining different analytical frameworks on
      the same dataset provide us new insights on emotional communication.

PMID- 23880526
TI  - Tears as a source of biomarkers for ocular and systemic diseases.
AB  - The main focus in clinical proteomics is the discovery of new protein or peptide
      biomarkers which are correlated with a certain disease. Tear proteins have been
      investigated extensively in the past and distinct relations between the levels of
      certain tear proteins to different disorders have been demonstrated. In this
      review we attempt to summarize proteomic technologies for biomarker
      identification in tears and some disease related biomarkers in tear fluids that
      were discovered through different proteomic techniques in different conditions
      like dry eye, Sjogren's syndrome, contact lens wearers, glaucoma, diabetic
      retinopathy or cancer. Proteomic analysis of tear fluid has proven to be a
      promising to gain more information about the pathogenesis of diseases and lead to
      new diagnostic possibilities. Furthermore, biomarkers represent promising targets
      for drug development and can be used to monitor the disease state or treatment
      responses, and accordingly improve the standards of patient care. 

PMID- 23880527
TI  - The retinal pigment epithelium: an important player of retinal disorders and
      regeneration.
AB  - The retinal pigment epithelium (RPE) is a partner of the neural retina and is
      indispensable for vision. In humans, proliferation and transformation (cell-type
      switching) of RPE cells after a traumatic injury of the neural retina causes a
      retinal disorder leading to loss of vision. In contrast, in certain adult
      amphibians such as Xenopus laevis and the newt, a similar process in RPE cells
      leads to regeneration of the entire retina. In this review, on the basis of
      accumulating evidence in basic biology and medical sciences, similarities and
      differences between these RPE-mediated retinal disorders and regeneration in
      adult vertebrates are highlighted, providing a connection to future research that
      should be designed to establish clues for the treatment of pathogenesis caused by
      RPE while promoting RPE-mediated retinal regeneration in a patient's eyes. 

PMID- 23880528
TI  - Regulation of Muller glial dependent neuronal regeneration in the damaged adult
      zebrafish retina.
AB  - This article examines our current knowledge underlying the mechanisms involved in
      neuronal regeneration in the adult zebrafish retina. Zebrafish, which has the
      capacity to regenerate a wide variety of tissues and organs (including the fins,
      kidney, heart, brain, and spinal cord), has become the premier model system to
      study retinal regeneration due to the robustness and speed of the response and
      the variety of genetic tools that can be applied to study this question. It is
      now well documented that retinal damage induces the resident Muller glia to
      dedifferentiate and reenter the cell cycle to produce neuronal progenitor cells
      that continue to proliferate, migrate to the damaged retinal layer and
      differentiate into the missing neuronal cell types. Increasing our understanding
      of how these cellular events are regulated and occur in response to neuronal
      damage may provide critical information that can be applied to stimulating a
      regeneration response in the mammalian retina. In this review, we will focus on
      the genes/proteins that regulate zebrafish retinal regeneration and will attempt
      to critically evaluate how these factors may interact to correctly orchestrate
      the definitive cellular events that occur during regeneration. 

PMID- 23880530
TI  - Human embryonic stem cell applications for retinal degenerations.
AB  - Loss of vision in severe retinal degenerations often is a result of photoreceptor
      cell or retinal pigment epithelial cell death or dysfunction. Cell replacement
      therapy has the potential to restore useful vision for these individuals
      especially after they have lost most or all of their light-sensing cells in the
      eye. A reliable, well-characterized source of retinal cells will be needed for
      replacement purposes. Human embryonic stem cells (ES cells) can provide an
      unlimited source of replacement retinal cells to take over the function of lost
      cells in the eye. The author's intent for this review is to provide an historical
      overview of the field of embryonic stem cells with relation to the retina. The
      review will provide a quick primer on key pathways involved in the development of
      the neural retina and RPE followed by a discussion of the various protocols out
      in the literature for generating these cells from non-human and human embryonic
      stem cells and end with in vivo application of ES cell-derived photoreceptors and
      RPE cells.

PMID- 23880531
TI  - The pain pathway in the rat following noxious thermal stimulation: effect of
      morphine on pERK1/2 and TRPV1 at the dorsal horn level, and on hyperalgesia.
AB  - The aim of the present study was to investigate the phosphorylation of ERK1/2 in
      the lumbar dorsal horn of the rat by fluorescence immunohistochemistry following
      a noxious thermal stimulation of the hind paw. The protein level of TRPV1 in the
      dorsal spinal cord and the development of a heat hyperalgesia after the acute
      noxious thermal stimulation were also measured. The protein content of TRPV1 was
      determined by Western blot and heat hyperalgesia by the plantar test. At 2 and 10
      min after the thermal stimulation a 4-fold increase in pERK1/2 immunoreactivity
      was observed in cells of lamina I/II of the L3-L5 dorsal horn. A pretreatment
      with the opioid analgesic morphine markedly attenuated ERK1/2 phosphorylation.
      The protein content of TRPV1 in the lumbar dorsal spinal cord was not
      significantly altered at 1 and 4 h after the thermal hind paw stimulation and by
      the morphine pretreatment. Heat hyperalgesia in the plantar test was observed at
      8 h, but not at 24 h after the noxious stimulation. This temporary hyperalgesia
      was prevented by the morphine pretreatment. The present findings indicate that
      ERK1/2 activation in dorsal horn nociceptive neurons may be linked to the
      development of hyperalgesia, and that opioid analgesics are effective agents to
      prevent sensitization in the pain pathway at spinal level.

PMID- 23880529
TI  - Antimicrobial compounds in tears.
AB  - The tear film coats the cornea and conjunctiva and serves several important
      functions. It provides lubrication, prevents drying of the ocular surface
      epithelia, helps provide a smooth surface for refracting light, supplies oxygen
      and is an important component of the innate defense system of the eye providing
      protection against a range of potential pathogens. This review describes both
      classic antimicrobial compounds found in tears such as lysozyme and some more
      recently identified such as members of the cationic antimicrobial peptide family
      and surfactant protein-D as well as potential new candidate molecules that may
      contribute to antimicrobial protection. As is readily evident from the literature
      review herein, tears, like all mucosal fluids, contain a plethora of molecules
      with known antimicrobial effects. That all of these are active in vivo is
      debatable as many are present in low concentrations, may be influenced by other
      tear components such as the ionic environment, and antimicrobial action may be
      only one of several activities ascribed to the molecule. However, there are many
      studies showing synergistic/additive interactions between several of the tear
      antimicrobials and it is highly likely that cooperativity between molecules is
      the primary way tears are able to afford significant antimicrobial protection to
      the ocular surface in vivo. In addition to effects on pathogen growth and
      survival some tear components prevent epithelial cell invasion and promote the
      epithelial expression of innate defense molecules. Given the protective role of
      tears a number of scenarios can be envisaged that may affect the amount and/or
      activity of tear antimicrobials and hence compromise tear immunity. Two such
      situations, dry eye disease and contact lens wear, are discussed here. 

PMID- 23880532
TI  - Bayesian modeling of the evolution of male height in 18th century Finland from
      incomplete data.
AB  - Data on army recruits' height are frequently available and can be used to analyze
      the economics and welfare of the population in different periods of history.
      However, such data are not a random sample from the whole population at the time
      of interest, but instead is skewed since the short men were less likely to be
      recruited. In statistical terms this means that the data are left-truncated.
      Although truncation is well-understood in statistics a further complication is
      that the truncation threshold is not known, may vary from time to time, and
      auxiliary information on the threshold is not at our disposal. The advantage of
      the fully Bayesian approach presented here is that both the population height
      distribution and the truncation are modeled simultaneously. The truncation
      threshold is allowed to be random and time-specific whilst the height
      distribution is assumed to change smoothly in time. Thus, in addition to the
      population height characteristics, we obtain also insight into recruiting
      criteria over time. Analysis of historical data from Swedish army recruitment in
      eight time events between 1768 and 1804 has found a declining trend in the mean
      population height during the inspected time period and also dramatic systematic
      changes in the recruiting. 

PMID- 23880533
TI  - CTCF demarcates chicken embryonic alpha-globin gene autonomous silencing and
      contributes to adult stage-specific gene expression.
AB  - Genomic loci composed of more than one gene are frequently subjected to
      differential gene expression, with the chicken alpha-globin domain being a clear
      example. In the present study we aim to understand the globin switching
      mechanisms responsible for the epigenetic silencing of the embryonic pi gene and
      the transcriptional activation of the adult alpha(D) and alpha(A) genes at the
      genomic domain level. In early stages, we describe a physical contact between the
      embryonic pi gene and the distal 3' enhancer that is lost later during
      development. We show that such a level of regulation is achieved through the
      establishment of a DNA hypermethylation sub-domain that includes the embryonic
      gene and the adjacent genomic sequences. The multifunctional CCCTCC-binding
      factor (CTCF), which is located upstream of the alpha(D) gene promoter, delimits
      this sub-domain and creates a transition between the inactive sub-domain and the
      active sub-domain, which includes the adult alpha(D) gene. In avian-transformed
      erythroblast HD3 cells that are induced to differentiate, we found active DNA
      demethylation of the adult alpha(D) promoter, coincident with the incorporation
      of 5-hydroxymethylcytosine (5hmC) and concomitant with adult gene transcriptional
      activation. These results suggest that autonomous silencing of the embryonic pi
      gene is needed to facilitate an optimal topological conformation of the domain.
      This model proposes that CTCF is contributing to a specific chromatin
      configuration that is necessary for differential alpha-globin gene expression
      during development. 

PMID- 23880534
TI  - The promise and challenges of blood spot methylomics.
AB  - Epigenome-wide association studies (EWAS) are being extensively performed to
      identify epigenetic variants associated to complex diseases. However, EWAS may
      identify variants that are disease-induced rather than disease-causal. Recent
      studies have highlighted the use of Guthrie cards to profile the methylome at
      birth, permitting researchers to find epigenetic variants present in patients
      before they are diagnosed with clinical disease, with the implicit suggestion
      that these variants are more likely to be disease causal. The use of Guthrie
      cards for research purposes throws up a number of ethical issues. We review here
      the promises and pitfalls of Guthrie cards for disease research. 

PMID- 23880535
TI  - How complex is the Bufo bufo species group?
AB  - Species delineation remains one of the most challenging tasks in the study of
      biodiversity, mostly owing to the application of different species concepts,
      which results in contrasting taxonomic arrangements. This has important practical
      consequences, since species are basic units in fields like ecology and
      conservation biology. We here review molecular genetic evidence relevant to the
      systematics of toads in the Bufo bufo species group (Anura, Bufonidae). Two
      studies recently published in this journal (Recuero et al., MPE 62: 71-86 and
      Garcia-Porta et al., MPE 63: 113-130) addressed this issue but reached opposing
      conclusions on the taxonomy of the group (four versus two species). In
      particular, allozyme data in the latter paper were interpreted as evidence for
      hybridization across species (between B. bufo-B. spinosus and B. bufo-B.
      verrucosissimus). We tested claims for hybridization through re-analysis of
      allozyme data for individuals instead of populations, to be able to distinguish
      between sympatry with and without admixture, and found no evidence of
      hybridization across taxa. We propose alternative explanations for the observed
      patterns that Garcia-Porta et al. (2012) failed to consider. In the absence of
      unequivocal evidence for hybridization and introgression, we reject the proposal
      to downgrade Bufo spinosus and Bufo verrucosissimus to the subspecies level. 

PMID- 23880536
TI  - Cell biological effects of mechanical stimulations generated by focused
      extracorporeal shock wave applications on cultured human bone marrow stromal
      cells.
AB  - Human bone marrow stromal cells (hBMSCs) bear tremendous clinical potential due
      to their immunomodulatory properties in transplantation settings and their
      contribution to tissue regeneration. In fact, they are among the most promising
      types of stem-like cells for therapeutic applications and are the subject of
      intense research. However, the clinical use of hBMSCs has been confounded by
      limitations in their availability; they are scarce cells cumbersome to isolate
      and purify. Additionally, they are difficult to target to the site of injury in
      regeneration experiments. In order to combat these limitations, focused
      extracorporeal shock waves (fESW, 0.2/0.3mJ*mm(-2)) were applied to purified,
      cultured hBMSCs. fESW (0.2mJ*mm(-2)) stimulations were found to increase hBMSCs'
      growth rate (p<0.05), proliferation (p<0.05), migration, cell tracking and wound
      healing (p<0.05, respectively), as well as to reduce the rate of apoptosis
      activation (p<0.05). The increase in hBMSC migration behavior was found to be
      mediated by active remodeling of the actin cytoskeleton as indicated by increased
      directed stress fiber formations (p<0.05). Furthermore, hBMSCs maintain their
      differentiation potentials after fESW treatment, whereas 0.2mJ*mm(-2) is the most
      effective application. In conclusion, our results establish first-timely that
      hBMSCs' behavior can be modified and optimized in response to defined mechanical
      stimulation. These findings appear particularly promising as they suggest that
      mechanical stress preconditions hBMSCs for improved therapeutic performance
      without genetic manipulations and that mechanically preconditioned hBMSCs will be
      advantageous for hBMSC-based tissue regeneration. Therefore, this approach opens
      the door for exploiting the full potential of these cells in regenerative
      medicine. 

PMID- 23880537
TI  - Short-term pathological and oncological outcomes after rectal cancer resection in
      patients with prior pelvic irradiation for another cancer.

PMID- 23880538
TI  - Access to 7beta-analogs of codeine with mixed MU/delta agonist activity via 6,7
      alpha-epoxide opening.
AB  - (-)-Codeine 1 was converted into previously unknown 7beta-methyl-7,8
      dihydrocodeine/morphine derivatives such as 13 via classical diaxial opening of
      alpha-epoxide 3. Several analogs exhibited dual MU/delta-agonist activity. 

PMID- 23880539
TI  - Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: wild
      type and mutant (L1196M) active compounds with unique binding mode.
AB  - We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK)
      inhibitors. Compounds 7b, 7 m and 7 n demonstrate excellent potencies in
      biochemical and cellular assays. X-ray crystal structure of one of the compounds
      (7 k) revealed a unique binding mode with the benzyl group occupying the back
      pocket, explaining its potency towards ALK and selectivity over tested kinases
      particularly Aurora-A. This binding mode is in contrast to that of known ALK
      inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding
      pocket, close to DFG motif.

PMID- 23880540
TI  - Native chemical ligation derived method for recombinant peptide/protein C
      terminal amidation.
AB  - C-terminal amidation is often a requisite structural feature for peptide hormone
      bio-activity. We report a chemical amidation method that converts peptide/protein
      thioesters into their corresponding C-terminal amides. The peptide/protein
      thioester is treated with 1-(2,4-dimethoxyphenyl)-2-mercaptoethyl auxiliary (1b)
      in a native chemical ligation (NCL) reaction to form an intermediate, which upon
      removal of the auxiliary with TFA, yields the peptide/protein amide. We have
      demonstrated the general utility of the approach by successfully converting
      several synthetic peptide thioesters to peptide amides with high conversion
      rates. Preliminary results of converting a recombinant peptide thioester to its
      amide form are also reported. 

PMID- 23880541
TI  - Investigation into the functional impact of the vancomycin C-ring aryl chloride.
AB  - A vancomycin aglycon analogue that possesses a reduced C-ring and an intact E
      ring chloride was prepared and its antimicrobial activity towards Staphylococcus
      aureus and binding affinity to model cell wall ligands were established.
      Comparison of the derivative with a series of vancomycin aglycon analogues that
      possess and lack the chloro substituents on the aryl C- and E-rings defines the
      impact and further refines the role the C-ring chloride plays in promoting both
      target binding affinity and binding selectivity for d-Ala-d-Ala and its impact on
      antimicrobial activity. 

PMID- 23880542
TI  - Neuroactive diol and acyloin metabolites from cone snail-associated bacteria.
AB  - The bacterium Gordonia sp. 647W.R.1a.05 was cultivated from the venom duct of the
      cone snail, Conus circumcisus. The Gordonia sp. organic extract modulated the
      action potential of mouse dorsal root ganglion neurons. Assay-guided
      fractionation led to the identification of the new compound circumcin A (1) and
      11 known analogs (2-12). Two of these compounds, kurasoin B (7) and soraphinol A
      (8), were active in a human norepinephrine transporter assay with Ki values of
      2575 and 867 nM, respectively. No neuroactivity had previously been reported for
      compounds in this structural class. Gordonia species have been reproducibly
      isolated from four different cone snail species, indicating a consistent
      association between these organisms.

PMID- 23880543
TI  - Fatal case of enterovirus 71 infection and rituximab therapy, france, 2012.

PMID- 23880544
TI  - Computational assessment of deep-seated tumor treatment capability of the
      9Be(d,n)10B reaction for accelerator-based boron neutron capture therapy (AB
      BNCT).
AB  - The 9Be(d,n)10B reaction was studied as an epithermal neutron source for brain
      tumor treatment through Boron Neutron Capture Therapy (BNCT). In BNCT, neutrons
      are classified according to their energies as thermal (<0.5 eV), epithermal (from
      0.5 eV to 10 keV) or fast (>10 keV). For deep-seated tumors epithermal neutrons
      are needed. Since a fraction of the neutrons produced by this reaction are quite
      fast (up to 5-6 MeV, even for low-bombarding energies), an efficient beam shaping
      design is required. This task was carried out (1) by selecting the combinations
      of bombarding energy and target thickness that minimize the highest-energy
      neutron production; and (2) by the appropriate choice of the Beam Shaping
      Assembly (BSA) geometry, for each of the combinations found in (1). The BSA
      geometry was determined as the configuration that maximized the dose deliverable
      to the tumor in a 1 h treatment, within the constraints imposed by the healthy
      tissue dose adopted tolerance. Doses were calculated through the MCNP code. The
      highest dose deliverable to the tumor was found for an 8 MUm target and a
      deuteron beam of 1.45 MeV. Tumor weighted doses >=40 Gy can be delivered up to
      about 5 cm in depth, with a maximum value of 51 Gy at a depth of about 2 cm. This
      dose performance can be improved by relaxing the treatment time constraint and
      splitting the treatment into two 1-h sessions. These good treatment capabilities
      strengthen the prospects for a potential use of this reaction in BNCT.

PMID- 23880545
TI  - On-demand proton pump inhibitory treatment in overweight/obese patients with
      gastroesophageal reflux disease: are there pharmacodynamic arguments for using
      higher doses?
AB  - BACKGROUND: Increased body mass index (BMI) is associated with a higher risk of
      gastroesophageal reflux disease (GORD). AIM: To investigate whether
      overweight/obesity affects proton pump inhibitor pharmacodynamics when used in a
      single dose in patients with GORD. METHODS: Post hoc analyses by patient BMI were
      performed on data from two single-center, double-blind, single-dose, crossover
      studies comparing the pharmacodynamics of rabeprazole 20 mg and pantoprazole 40
      mg in GORD patients with a history of nocturnal heartburn. The primary endpoint
      was the mean percentage of time with intragastric pH >4 between lean and
      overweight/obese patients (BMI <25 and >=25). RESULTS: 24 h baseline intragastric
      pH values were not different between BMI groups. The pharmacodynamic effects of
      both proton pump inhibitors were not significantly different between BMI groups,
      and no evidence was found for an interaction between BMI and treatment. As
      compared with pantoprazole, rabeprazole showed a significantly greater effect on
      the antisecretory response for both BMI groups. CONCLUSIONS: Overweight/obesity
      in GORD patients does not appear to affect the antisecretory efficacy of a single
      dose of rabeprazole and pantoprazole. These data do not support adapting the
      dosage of rabeprazole and pantoprazole according to BMI in GORD patients when
      administered as an on-demand therapy schedule.

PMID- 23880546
TI  - Mitochondrial inactivation by Anopheles albimanus cecropin 3: molecular
      mechanisms.
AB  - Cecropin 3 (Ccrp3) is an antimicrobial peptide from Anopheles albimanus, which is
      expressed during Plasmodium berghei infection. Here, we report that synthetic
      Ccrp3, aside from antibacterial activity, also shows cardio regulatory functions.
      In rats, Ccrp3 significantly diminishes blood pressure as well as the heartbeat
      frequency at nanomolar concentration. Ccrp3 affect the rat cardiac muscle
      mitochondria, inducing uncoupling of oxidative phosphorylation, oxygen
      consumption and transport of Ca(2). Ccrp3 treatment of the mitochondria causes
      mitochondrial damage promoting oxidative stress, causing overproduction of
      reactive oxygen species (ROS) and inhibition of superoxide dismutase. At nM
      concentration, Ccrp3 inhibits superoxide dismutase activity through direct
      interaction, diminishing by its enzymatic activity. Ccrp3 induces the release of
      the pro-apoptotic marker Bax from the mitochondria. Altogether, these results
      suggest that Ccrp3 pro-oxidative activity on cardiac muscle mitochondria could be
      responsible for triggering the heartbeat frequency and blood pressure lowering
      observed the Ccrp3 injected rats. 

PMID- 23880547
TI  - Diagnosis and treatment of arterial-ureteric fistula.
AB  - A 45-year-old woman presented with gross hematuria. She had previously undergone
      an aortobifemoral bypass that subsequently became infected. The infected graft
      was removed and replaced with homograft. An arterioureteric fistula was
      identified with angiography and the patient was treated with an iCast stent
      graft. Diagnosis of arterioureteric fistula should be suspected in patients with
      gross hematuria and associated risk factors. We would recommend angiography for
      diagnosis and simultaneous treatment with a stent graft, although the long-term
      durability and outcome is unknown.

PMID- 23880549
TI  - Hybrid aortic arch repair for complicated type B aortic dissection.
AB  - OBJECTIVE: This study analyzed the outcome of a combined endovascular and
      debranching procedure for hybrid aortic arch repair (HAR) in patients with
      complicated type B aortic dissection. METHODS: Between February 2006 and August
      2012, HAR was performed in 75 consecutive patients, with retrospective analysis
      of a subgroup of 45 patients who underwent HAR with complicated acute (n = 10),
      subacute (n = 7), or chronic (n = 28) type B dissection as the underlying
      disease. Descriptive statistics were computed for continuous and categoric
      variables. The interval to death or last follow-up was estimated using the Kaplan
      Meier method. RESULTS: The patients were a mean age of 59.9 +/- 10.7 years
      (median, 59.2; range, 35-78 years). Complete supra-aortic debranching was
      performed in six (13%) in zone 0 (procedure time, 200 minutes; range, 185-365
      minutes) and partial debranching in 39 (87%), comprising 16 (36%) in zone 1
      (procedure time, 120 minutes; range, 75-250 minutes) and 23 (51%) in zone 2
      (procedure time, 91 minutes; range, 70-210 minutes). Technical success was
      achieved in 86.7% (39 of 45). Thirty-day mortality was 4.4% (two of 45), with an
      in-hospital mortality of 11.1% (five of 45) as a result of three additional
      deaths after days 33, 35, and 111. Comparing HAR for type B dissection after
      complete debranching in six and partial debranching in 39, the overall in
      hospital mortality was 67% (four of six) and 2.6% (one of 39), respectively.
      After a median follow-up of 20.8 months (range, 0.3-70 months), the overall
      mortality was 13.3% (six of 45), with Kaplan-Meier survival estimate of 85% at 1
      year. Stroke rate was 8.8% (four of 45). Paraplegia developed in one patient
      (2.2%), with complete recovery after spinal drainage. Cardiac complications
      occurred in three patients (6.7%), pulmonary complications in 10 (22.2%), and
      renal insufficiency requiring dialysis developed in five (11%). Retrograde
      dissection occurred in one patient (2.2%) 14 days after complete debranching and
      zone 0 thoracic endovascular aortic repair, with fatal outcome. No bypass
      dysfunction was seen during follow-up. The overall early and late endoleak rates
      were 27% (12 of 44) and 43% (13 of 30), respectively. Eight patients (18%)
      required reintervention, with freedom of reintervention in 91% at 1 year and 81%
      at 2 years. CONCLUSIONS: HAR in zone 1 and 2 appears a viable alternative to
      conventional aortic arch surgery in patients with complicated type B dissection.
      Stroke and endoleaks remain complications that need to be addressed. Treatment of
      type B aortic dissection with complete supra-aortic debranching and thoracic
      endovascular aortic repair in zone 0, however, is associated with high mortality,
      which might be reduced by improved technology using branched stent grafts.

PMID- 23880550
TI  - Percutaneous transluminal angioplasty results in improved physical function but
      not balance in patients with intermittent claudication.
AB  - OBJECTIVE: The aim of this study was to identify whether revascularization by
      percutaneous transluminal angioplasty (PTA) for patients with intermittent
      claudication improved measures of functional performance including balance.
      METHODS: A prospective observational study was performed at a single tertiary
      vascular center. Patients with symptomatic intermittent claudication (Rutherford
      grades 1-3) were recruited to the study. Participants were assessed at baseline
      (pre-PTA) and then 3, 6, and 12 months post-PTA for markers of (1) lower limb
      ischemia (treadmill walking distances and ankle-brachial pressure index), (2)
      physical function (6-minute walk, Timed Up and Go, and chair stand time), (3)
      balance impairment using computerized dynamic posturography with the Sensory
      Organization Test, and (4) quality of life (VascuQoL and Short Form Health Survey
      [SF-36]). RESULTS: Forty-three participants underwent PTA. Over 12 months, a
      significant improvement was demonstrated in initial (P = .04) and maximum
      treadmill walking distance (P = .019). Physical functional ability improved
      across all outcome measures (P < .02), and some domains of both generic (P < .03)
      and disease-specific quality of life (P < .01). No significant improvement in
      balance was demonstrated by the Sensory Organization Test (P = .24). CONCLUSIONS:
      Balance impairment is common in claudicants and does not improve with
      revascularization. Further research regarding effective treatment of balance
      impairment is required in this specific group of patients.

PMID- 23880548
TI  - Validation of three models predicting in-hospital death in patients with an
      abdominal aortic aneurysm eligible for both endovascular and open repair.
AB  - OBJECTIVE: The Medicare, the Vascular Governance North West (VGNW), and the
      British Aneurysm Repair (BAR) models can be used to predict in-hospital death
      after an intervention for an asymptomatic abdominal aortic aneurysm (AAA).
      Validation of these models in patients with suitable aortic anatomy for
      endovascular repair and a general condition fit for open repair is lacking. We
      validated the Medicare, VGNW, and BAR models in patients from a randomized
      controlled trial comparing open and endovascular AAA repair. METHODS: A per
      protocol analysis was done of 345 Dutch and Belgian patients with in-hospital
      death as the primary end point. The prediction models were validated taking into
      account discrimination (the ability to distinguish between death and survival)
      and calibration (the agreement between predicted and observed death rates).
      Discrimination was assessed using the area under the receiver-operating
      characteristics curve (AUC). An AUC >0.70 was considered to be sufficiently
      accurate. Calibration was assessed using the Hosmer-Lemeshow (HL) test, and P >
      .05 was considered to be sufficiently accurate. RESULTS: The AUC was 0.77 (95%
      confidence interval [CI], 0.64-0.90; HL test, P = .52) for the Medicare model,
      0.88 (95% CI, 0.81-0.95; HL test, P = .31) for the VGNW model, and 0.79 (95% CI,
      0.67-0.91; HL test, P = .15) for the BAR model. CONCLUSIONS: In AAA patients
      eligible for endovascular and open repair, the predictions of in-hospital death
      by the Medicare, VGNW, and BAR models were sufficiently accurate. Therefore,
      these models can be used to support deciding between endovascular and open
      repair.

PMID- 23880551
TI  - Early lesions following aerosol infection of rhesus macaques (Macaca mulatta)
      with Mycobacterium tuberculosis strain H37RV.
AB  - As part of a study to investigate early changes following exposure to aerosols of
      Mycobacterium tuberculosis (Mtb), 10 rhesus macaques (Macaca mulatta) were
      infected with high (731 colony forming units [cfu]), medium (70 cfu) or low (7
      cfu) doses of Mtb, and tissues were examined at 2 and 3 weeks post infection
      (wpi). Clinical disease was not observed. Results of advanced imaging and
      pathological findings were compared with respect to the delivered dose and time
      post infection. Magnetic resonance imaging revealed lesions in the lungs at these
      early time points ex vivo immediately prior to detailed post-mortem examination
      in the absence of clinical disease. In animals exposed to high and medium doses
      of Mtb that were studied at 2 and 3 wpi, a range of lesions including small foci
      of mainly mononuclear cells, primarily macrophages (granulomatous lesions), as
      well as obvious granulomas, were observed microscopically in the lungs, including
      lymphatics and hilar lymph nodes. In the low-dose group at 3 weeks, small lesions
      were identified in the lung and hilar lymph nodes of one animal, and the
      remaining two animals in this group had lesions in either lung or hilar lymph
      node. Acid fast bacilli were demonstrated in the lung and lymph nodes in all
      animals that received high and medium doses, and the lymph nodes of two animals
      at the low dose. A dose-dependent effect was observed with increasing dose and
      time post infection. Furthermore, early dissemination of bacilli to the draining,
      hilar lymph nodes with concomitant granulomatous lesion formation was observed.
      By contributing to the recognition of early lesion development due to aerosol
      challenge of Mtb in the rhesus macaque, this study forms a basis for further
      investigation of early lesions and may inform the design of future vaccine and
      therapeutic studies involving early time points in this species.

PMID- 23880552
TI  - Does use of 'non-trial' cessation support help explain the lack of effect from
      offering NRT to quitline callers in a RCT?

PMID- 23880554
TI  - Current status of islet encapsulation.
AB  - Cell encapsulation is a method of encasing cells in a semipermeable matrix that
      provides a permeable gradient for the passage of oxygen and nutrients, but
      effectively blocks immune-regulating cells from reaching the graft, preventing
      rejection. This concept has been described as early as the 1930s, but it has
      exhibited substantial achievements over the last decade. Several advances in
      encapsulation engineering, chemical purification, applications, and cell
      viability promise to make this a revolutionary technology. Several obstacles
      still need to be overcome before this process becomes a reality, including
      developing a reliable source of islets or insulin-producing cells, determining
      the ideal biomaterial to promote graft function, reducing the host response to
      the encapsulation device, and ultimately a streamlined, scaled-up process for
      industry to be able to efficiently and safely produce encapsulated cells for
      clinical use. This article provides a comprehensive review of cell encapsulation
      of islets for the treatment of type 1 diabetes, including a historical
      perspective, current research findings, and future studies. 

PMID- 23880555
TI  - Behavioural and hormonal stress responses during chick rearing do not predict
      brood desertion by female in a small Arctic seabird.
AB  - We examined behavioural and hormonal stress responses in a small seabird (little
      auk, Alle alle), which exhibits a transition from biparental to male-only care
      towards the end of the nesting period, in order to understand the mechanisms
      underlying this parental strategy. We hypothesized that the male staying with the
      chick should be less sensitive to stressors. As such the male might offer the
      offspring more efficient protection during the fledging period than the female.
      We tested this hypothesis by observing male and female behaviour in a neophobia
      test. We also measured the birds' baseline and stress-induced levels of
      corticosterone and prolactin using the standardized capture-and-restraint
      protocol. Both sexes respond rapidly to foreign objects, delaying the entry time
      to the nest with food, consuming the food load, and/or temporarily abandoning
      feeding. However, we did not find any differences between the sexes in the
      frequency of each behaviour or in the time of the first reaction to the
      experimental treatment. Level of both corticosterone and prolactin increased
      after the experimental treatment. However, we did not find sex differences in
      baseline and stress-induced hormone levels. The results indicate that the males
      are as much sensitive to the stress situation as the females. Thus, the pattern
      of male and female behavioural and hormonal responses to stress does not predict
      their behaviour at the final breeding stage. 

PMID- 23880556
TI  - Finding a job in an overcrowded market: getting what you want.
AB  - As the number of fellowship-trained orthopaedic trauma surgeons entering the
      workforce increases, so does the competition for available practice
      opportunities. The process of finding employment has seemingly become more
      involved as the relative availability of positions has declined over recent
      years. To manage this new environment, new graduates need to become much more
      proactive in the process of seeking and obtaining orthopaedic trauma positions.

PMID- 23880553
TI  - Structural insights into phospholipase C-beta function.
AB  - Phospholipase C (PLC) enzymes convert phosphatidylinositol-4,5-bisphosphate into
      the second messengers diacylglycerol and inositol-1,4,5-triphosphate. The
      production of these molecules promotes the release of intracellular calcium and
      activation of protein kinase C, which results in profound cellular changes. The
      PLCbeta subfamily is of particular interest given its prominent role in
      cardiovascular and neuronal signaling and its regulation by G protein-coupled
      receptors, as PLCbeta is the canonical downstream target of the heterotrimeric G
      protein Galphaq. However, this is not the only mechanism regulating PLCbeta
      activity. Extensive structural and biochemical evidence has revealed regulatory
      roles for autoinhibitory elements within PLCbeta, Gbetagamma, small molecular
      weight G proteins, and the lipid membrane itself. Such complex regulation
      highlights the central role that this enzyme plays in cell signaling. A better
      understanding of the molecular mechanisms underlying the control of its activity
      will greatly facilitate the search for selective small molecule modulators of
      PLCbeta. 

PMID- 23880557
TI  - Preparing for changing times.

PMID- 23880558
TI  - An examination and discussion of unintended consequences of being an employed
      physician.
AB  - Medicine's landscape is ever changing. The working model in which an orthopaedic
      surgeon operates is no exception. These models can be very confusing for the
      orthopaedic surgeon who has little training in the area of business, but
      especially to the young orthopaedic surgeon who has focused their efforts nearly
      100% on medical training over many years. This article examines some of the
      issues that might not be obvious to the physician who is trying to decide between
      hospital employment and private practice or some combination thereof. Also, there
      are several discussion points and questions raised for the physician contract
      negotiator when examining an employment contract. Finally, introduced are some
      advocacy steps that we, as orthopaedic surgeons, should consider to continue to
      improve medicine and our work environments.

PMID- 23880559
TI  - Ten "tips and tricks" to provide trauma care without residents.
AB  - The utilization of medical students, residents, and fellows within the
      orthopaedic trauma team helps alleviate workload demands. However, many
      nonacademic hospitals lack these clinical resources. Therefore, orthopaedic
      trauma surgeons often must be creative in developing alternative methods to
      better manage time, staff, and patients. Incorporating midlevel providers and
      maximizing surgical technician assistance are favorable for both the hospital and
      the patient. In addition, using currently available medical devices in unique and
      innovative ways can help simplify patient procedures and optimize care. The
      purpose of this article is to detail precise tips and tricks for overcoming
      challenges observed during orthopaedic trauma cases when residents are
      unavailable.

PMID- 23880560
TI  - Getting organized in your job.
AB  - The benefits of being organized when starting one's career are countless and
      worth the time and effort in developing an effective and efficient practice.
      Established protocols, good habits, and methodical communication that include all
      members of the team will help create a system that keeps all components of one's
      practice organized. Adhering to these strategies requires self-discipline.
      Applying these concepts to patient care, education, research, and administrative
      responsibilities is the key to a successful and sustainable career.

PMID- 23880561
TI  - Expert medical testimony for your injured patients.
AB  - Many injured patients sustain some type of loss. If someone else is responsible
      for the injury, the injured patient can pursue compensation for this loss. In the
      course of treating an injured patient, you may be asked to participate in the
      legal process to resolve such claims. The basic components of a personal injury
      claim are reviewed. An overview of the legal process will help clarify your role
      in the legal process. Enhanced understanding will allow you to provide important
      medical testimony for your injured patient.

PMID- 23880562
TI  - Getting what you need from the hospital to succeed as a traumatologist.
AB  - Currently, the market for orthopaedic trauma surgeons is varied. The market
      consists of university employed, university private, medical group employed,
      medical group private, private employed, private contracted, and private. Each
      option has its positives and negatives. The orthopaedic trauma surgeon needs to
      determine which setting is appropriate for his/her given needs and wants. An
      experienced mentor(s) is invaluable for advice and guidance. The surgeon then
      needs to find an administrative leader to initiate, implement, and evaluate
      certain processes to succeed.

PMID- 23880563
TI  - The value of preoperative planning.
AB  - "Better to throw your disasters into the waste paper basket than to consign your
      patients to the scrap heap" has been a proverb of Jeff Mast, one of the greatest
      fracture and deformity surgeons in the history of our specialty. Stated slightly
      more scientifically, one of the major values of simulation is that it allows one
      to make mistakes in a consequence-free environment. Preoperative planning is the
      focus of this article. The primary goal is not to provide you with a recipe of
      how to steps. Rather, the primary goal of this article is to explain why
      preoperative planning should be standard, to clarify what should be included, and
      to provide examples of what can happen when planning is ignored. At the end of
      this, we should all feel the need to approach fracture care more intellectually
      with forethought, both in our own practices and in our educational system.

PMID- 23880564
TI  - The view from the other side of the desk: what an employer looks for during an
      interview.
AB  - It may be helpful for orthopaedic surgeons seeking employment to consider what
      the recruiting orthopaedic surgeon on the other side of the desk is thinking!
      Well-managed orthopaedic practices realize how expensive it is to recruit new
      surgeons only to lose them 2 years later, and these practices will try diligently
      to ensure that there is a good fit between the candidate and the practice before
      offering a position. It is also important to realize that many practices cannot
      promise everything that a starting orthopaedic surgeon will want and ignoring
      practices that are realistic in their guarantees will cause the candidate to
      overlook some very good opportunities. Although no one can ever guarantee a
      perfect decision every time, using common sense and a reasonable due diligence
      will often result in a good match.

PMID- 23880565
TI  - Perspectives of being spouse, parent, and surgeon.
AB  - Achieving a balance between one's career and personal life is a never-ending
      challenge. As a surgeon, add-on cases and double-booked clinics can lead to long
      hours at work and make availability for family time unpredictable. It may seem
      like the threat of interruption because of patient needs always loom. Disruptions
      to family time extend beyond the long hours spent in surgery and clinics.
      Inattentiveness at home because of the technology tethers that keep one available
      for constant questions and patient care issues can also distract from time spent
      with family. Although the practice of an orthopaedic trauma surgeon can involve
      unpredictable schedules and patient care issues, there are means of mitigating
      the chaos that can envelop one's personal life as a result of a chosen career
      track. Clear priorities and expectations in both personal and professional arenas
      can improve the work-life balance. Flexible jobs that allow for more time with
      family do exist. Negotiating for this flexibility and self-assurance in holding
      fast to personal ideals are important in achieving a successful balance.

PMID- 23880566
TI  - Multi-modality gellan gum-based tissue-mimicking phantom with targeted
      mechanical, electrical, and thermal properties.
AB  - This study develops a new class of gellan gum-based tissue-mimicking phantom
      material and a model to predict and control the elastic modulus, thermal
      conductivity, and electrical conductivity by adjusting the mass fractions of
      gellan gum, propylene glycol, and sodium chloride, respectively. One of the
      advantages of gellan gum is its gelling efficiency allowing highly regulable
      mechanical properties (elastic modulus, toughness, etc). An experiment was
      performed on 16 gellan gum-based tissue-mimicking phantoms and a regression model
      was fit to quantitatively predict three material properties (elastic modulus,
      thermal conductivity, and electrical conductivity) based on the phantom
      material's composition. Based on these material properties and the regression
      model developed, tissue-mimicking phantoms of porcine spinal cord and liver were
      formulated. These gellan gum tissue-mimicking phantoms have the mechanical,
      thermal, and electrical properties approximately equivalent to those of the
      spinal cord and the liver. 

PMID- 23880567
TI  - The role of the dorsal dentate gyrus in object and object-context recognition.
AB  - The aim of this study was to determine the role of the dorsal dentate gyrus (dDG)
      in object recognition memory using a black box and object-context recognition
      memory using a clear box with available cues that define a spatial context. Based
      on a 10 min retention interval between the study phase and the test phase, the
      results indicated that dDG lesioned rats are impaired when compared to controls
      in the object-context recognition test in the clear box. However, there were no
      reliable differences between the dDG lesioned rats and the control group for the
      object recognition test in the black box. Even though the dDG lesioned rats were
      more active in object exploration, the habituation gradients did not differ.
      These results suggest that the dentate gyrus lesioned rats are clearly impaired
      when there is an important contribution of context. Furthermore, based on a 24 h
      retention interval in the black box the dDG lesioned rats were impaired compared
      to controls.

PMID- 23880569
TI  - Brugada electrocardiographic findings in an 80-year-old man.

PMID- 23880568
TI  - The role of MyoD1 and histone modifications in the activation of muscle
      enhancers.
AB  - MyoD1 is a key regulator that orchestrates skeletal muscle differentiation
      through the regulation of gene expression. Although many studies have focused on
      its role in transcriptional control at gene promoters, less is known regarding
      the role of MyoD1 in the assembly of active enhancers. Here, we discuss novel
      data that point to the ability of MyoD1 to mediate the assembly of active
      enhancers that augment the transcription of genes essential for muscle
      development and lineage specification. Based on genome-wide studies of epigenetic
      marks that typify active enhancers, we recently identified the compendium of
      distal regulatory elements that dictate transcriptional programs during
      myogenesis. Superimposition of MyoD1 binding sites upon the locations of muscle
      enhancers revealed its unequivocal binding to a core region of nearly a third of
      condition-specific muscle enhancers. Further studies exploring deposition of
      enhancer-related epigenetic marks in myoblasts lacking MyoD1 demonstrate the
      dependence of muscle enhancer assembly on the presence of MyoD1. We propose a
      model wherein MyoD1 mediates recruitment of Set7, H3K4me1, H3K27ac, p300, and
      RNAP II to MyoD1-bound enhancers to establish condition-specific activation of
      muscle genes. Moreover, muscle enhancers are modulated through coordinated
      binding of transcription factors, including c-Jun, Jdp2, Meis, and Runx1, which
      are recruited to muscle enhancers in a MyoD1-dependent manner. Thus, MyoD1 and
      enhancer-associated transcription factors function coordinately to assemble and
      regulate enhancers, thereby augmenting expression of muscle-related genes. 

PMID- 23880570
TI  - Haemorrhagic stroke or hyperglycaemia?
AB  - A 56-year-old woman with no medical history was admitted with acute onset
      hemiballistic-choreiform movements of right extremity. On admission, her serum
      glucose and osmolality were elevated. Her glycosylated haemoblobin (HbA1c) was
      17.9 with average blood sugars of 467 mg/dL. A CT scan of the brain revealed
      unilateral hyperintensities in the basal ganglia. A complete stroke work-up,
      including MRI and MR angiography of brain was otherwise unrevealing. Subcutaneous
      insulin was instituted, which led to complete resolution of her symptoms within
      48 h of hospital admission. She was readmitted 4 weeks after her initial
      discharge for similar, but less severe, symptoms. This time her HbA1c was 13.9
      with an average blood sugar of 352 mg/dL. A repeat MRI demonstrated a persistent
      abnormal signal within the left basal ganglia without infarct. She was started on
      subcutaneous insulin. Her symptoms improved but did not resolve. Haloperidol and
      gabapentin were initiated and she was again discharged after stabilisation to a
      rehabilitation centre as per physiotherapy recommendations. 

PMID- 23880571
TI  - A rapid increase in the normal white cell counts without blasts as the initial
      presentation of T-cell acute lymphoblastic leukaemia.
AB  - A 5-year-old girl with multiple enlarged cervical lymph nodes consistent with
      Epstein-Barr virus infection showed a rapid increase in the white blood cell
      counts (myeloid cells and lymphocytes) without blasts over a week period. Bone
      marrow evaluation performed after a week's observation unexpectedly showed
      replacement of the marrow with T lymphoblasts. A presentation of T-cell acute
      lymphoblastic leukaemia (T-ALL) in this fashion is very unusual. We postulate
      that the T-lymphoblasts may have been secreting granulocyte colony stimulating
      factor like substance. We are unable to find a similar case report in the
      literature, and thus we wish to report this case. The patient has been treated
      with Children's Oncology Group T-ALL protocol, and has been in continuous
      remission. 

PMID- 23880572
TI  - Familial ectodermal dysplasia: a peers' agony.
AB  - Ectodermal dysplasias include a various group of inherited disorders which share
      primary defect in the development of two or more tissues of embryonic ectodermal
      origin. Though there are many subtypes, ectodermal dysplasias are mainly hidrotic
      ectodermal dysplasia and hypohidrotic ectodermal dysplasia, among which the most
      common variety is X linked hypohidrotic ectodermal dysplasia. We report a rare
      case of X linked hypohidrotic ectodermal dysplasia occurring in a family with
      various skin, hair and oral abnormalities. 

PMID- 23880573
TI  - Mediterranean spotted fever with involvement of the gastrointestinal tract.

PMID- 23880574
TI  - Management of acute gastric varices bleeding.
AB  - Gastroesophageal varices bleeding is a major complication in patients with
      cirrhosis. Gastric varices (GVs) occur in approximately 20% of patients with
      portal hypertension. However, GV bleeding develops in only 25% of patients with
      GV and requires more transfusion and has higher mortality than esophageal
      variceal (EV) bleeding. The best strategy for managing acute GV bleeding is
      similar to that of acute EV bleeding, which involves airway protection,
      hemodynamic stabilization, and intensive care. Blood transfusion should be
      cautiously administered in order to avoid rebleeding. Vasoactive agents such as
      terlipressin or somatostatin should be used when GV bleeding is suspected.
      Routine use of prophylactic antibiotics reduces bacterial infection and lowers
      rebleeding rates. By administering endoscopic cyanoacrylate injection, the
      initial hemostasis rate achieved is at least 90% in most cases; the average
      mortality rate of GV bleeding is approximately 10-30% and the rebleeding rate is
      between 22% and 37%. Although endoscopic injection of cyanoacrylate is superior
      to sclerotherapy and band ligation, and has remained the treatment of choice for
      treating acute GV bleeding, the outcome of this treatment is still
      unsatisfactory. New treatment options, such as thrombin injection, transjugular
      intrahepatic portosystemic shunts, or balloon-occluded retrograde transvenous
      obliteration, have shown promising results for acute GV bleeding. However,
      randomized controlled trials are needed to compare the efficacy of these
      therapies with cyanoacrylate. 

PMID- 23880575
TI  - Primary cardiac fibroma in an infant: computed tomography and magnetic resonance
      imaging findings.
AB  - Cardiac fibromas (CFs) are benign primary tumors that typically occur during
      childhood and may be asymptomatic. However, due to the proximity of CFs to the
      cardiac structure, significant morbidity and mortality may also be anticipated.
      CFs do not show spontaneous regression and surgical resection generally remains
      the treatment of choice for these tumors in children. Thus, it is important to
      take aggressive steps to obtain accurate pretreatment image diagnosis. A full
      term male infant was presented to our facility suffering from shortness of
      breath, after an episode of upper respiratory tract infection at age 1.5 months.
      Subsequent chest X-ray revealed widening of the mediastinum and trachea
      deviation. Cardiogenic pathology was suspected. Computed tomography and magnetic
      resonance imaging were performed, and we confirmed a diagnosis of benign CF.
      Thoracotomy biopsy of the tumor confirmed the pathological diagnosis. 

PMID- 23880576
TI  - Circumferential resection margin in esophageal cancer.

PMID- 23880577
TI  - Presensitized immune condition of host exaggerates prolonged cold ischemia
      mediated injury of cardiac graft involving regulatory T cells.
AB  - BACKGROUND: The detrimental effect of prolonged cold ischemia time (PCI) on
      presensitized transplanted graft is conceivable, but the impact of
      presensitization status of recipient on PCI-mediated graft injury and
      inflammation is not well defined. METHODS: Allogeneic skin grafts from BALB/c
      donors were transplanted into C57BL/6 recipients for presensitization. Syngeneic
      or allogeneic heterotopic heart transplantations with PCI were performed using
      C57BL/6 or BALB/c donors for these recipients through different treatments.
      RESULTS: We revealed that PCI could not affect isograft survival but
      significantly shortened allograft survival in the presensitized recipients.
      Depletion of regulatory T cells (Tregs) starting 1 day before and after heart
      transplantation with anti-CD25 monoclonal antibody remarkably induced intragraft
      Foxp3 gene expression, worsened architecture damage and subepicardial and
      intramuscle inflammatory cellular infiltration, and caused a dramatic fall of
      intragraft CD4+/CD8+ ratio, whereas adoptive transfer of exogenous wild-type
      Tregs or endogenous Tregs promoted by rapamycin had a beneficial effect on
      preventing the infiltration of T lymphocytes and Gr-1+ neutrophils and reversed
      intragraft CD4+/CD8+ ratio, preserving cardiac graft architecture. However, their
      distinct protective mechanisms showed that rapamycin treatment mainly diminished
      CD4+ T-cell infiltration. Nevertheless, CD4+ still outnumbered CD8+ T cells in
      the graft, whereas adoptive transfer of Tregs expanded both CD4+ and CD8+ T
      cells, particularly CD8+ T cells. CONCLUSION: Allogeneic immunoresponses
      synergistically enhanced PCI effect under presensitized condition. PCI could
      affect subsequent immunoresponses. Tregs were closely involved in this
      pathophysiologic process. Our data may pave the way to use Tregs as a novel
      therapeutic approach to prevent PCI-mediated injury in the presensitized
      transplant recipients.

PMID- 23880578
TI  - Changes in the cardiac oxidative metabolism induced by PGC-1{alpha}: response of
      different physical training protocols in infarction-induced rats.

PMID- 23880579
TI  - Central venous oxygen saturation (ScVO2) facilitates the weaning of intra-aortic
      balloon pump in acute heart failure related to acute myocardial infarction.

PMID- 23880580
TI  - Red cell distribution width without additional cost compared with a relatively
      expensive test measurement in clinical practice.

PMID- 23880581
TI  - Cardiovascular medication in relation to renal function after coronary artery
      bypass surgery.
AB  - BACKGROUND: Guidelines for recommended medication use for the secondary
      prevention of coronary heart disease are exceedingly important in patients with
      chronic kidney disease. Despite a high risk for recurrent cardiovascular events,
      these patients are less likely to use evidence-based recommended medications. The
      objective of the current study was to analyze the association between renal
      function and guideline-recommended drug therapy in patients with coronary heart
      disease. METHODS: In this nationwide population-based cohort study, we included
      12,332 patients with established coronary heart disease who underwent primary
      isolated coronary artery bypass grafting in Sweden between 2005 and 2008.
      Medication use was retrieved from the national Prescribed Drug Register. RESULTS:
      During the first year after coronary surgery, 94% of patients had at least two
      dispensed prescriptions for an antiplatelet agent, 68% for an angiotensin
      converting enzyme inhibitor or angiotensin II receptor blocker, 92% for a beta
      blocker, and 93% for a statin. Only 57% of all patients had prescriptions for all
      four medication classes. Reduced renal function (estimated glomerular filtration
      rate (eGFR) of 30 to 45 mL/min per 1.73 m(2) and <30 mL/min per 1.73 m(2)) was
      significantly associated with a lower use of all four medication classes
      (adjusted risk ratio 0.89, 95% confidence interval 0.82 to 0.98; and adjusted
      risk ratio 0.75, 95% confidence interval 0.62 to 0.90, respectively) as compared
      to normal renal function (eGFR >60 mL/min per 1.73 m(2)). CONCLUSIONS: In
      patients with established coronary heart disease, moderate to severe renal
      dysfunction was associated with significantly lower use of guideline-recommend
      medications as compared to normal renal function.

PMID- 23880582
TI  - Antibodies against antibodies inducing Kounis syndrome.

PMID- 23880583
TI  - Norovirus variant GII.4/Sydney/2012, Bangladesh.

PMID- 23880584
TI  - IRE1: ER stress sensor and cell fate executor.
AB  - Cells operate a signaling network termed the unfolded protein response (UPR) to
      monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol
      requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to
      maintain the ER and cellular function. Although mammalian IRE1 promotes cell
      survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent
      and divergent IRE1 characteristics between plants and animals underscore its
      significance in cellular homeostasis. This review provides an updated scenario of
      the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares
      IRE1 features among species, and outlines exciting future directions in UPR
      research. 

PMID- 23880585
TI  - Nurse-led follow-up at home vs. conventional medical outpatient clinic follow-up
      in patients with incurable upper gastrointestinal cancer: a randomized study.
AB  - CONTEXT: Upper gastrointestinal cancer is associated with a poor prognosis. The
      multidimensional problems of incurable patients require close monitoring and
      frequent support, which cannot sufficiently be provided during conventional one
      to two month follow-up visits to the outpatient clinic. OBJECTIVES: To compare
      nurse-led follow-up at home with conventional medical follow-up in the outpatient
      clinic for patients with incurable primary or recurrent esophageal, pancreatic,
      or hepatobiliary cancer. METHODS: Patients were randomized to nurse-led follow-up
      at home or conventional medical follow-up in the outpatient clinic. Outcome
      parameters were quality of life (QoL), patient satisfaction, and health care
      consumption, measured by different questionnaires at one and a half and four
      months after randomization. As well, cost analyses were done for both follow-up
      strategies in the first four months. RESULTS: In total, 138 patients were
      randomized, of which 66 (48%) were evaluable. At baseline, both groups were
      similar with respect to clinical and sociodemographic characteristics and health
      related QoL. Patients in the nurse-led follow-up group were significantly more
      satisfied with the visits, whereas QoL and health care consumption within the
      first four months were comparable between the two groups. Nurse-led follow-up was
      less expensive than conventional medical follow-up. However, the total costs for
      the first four months of follow-up in this study were higher in the nurse-led
      follow-up group because of a higher frequency of visits. CONCLUSION: The results
      suggest that conventional medical follow-up is interchangeable with nurse-led
      follow-up. A cost utility study is necessary to determine the preferred frequency
      and duration of the home visits.

PMID- 23880586
TI  - Nurses' responses to requests for forgiveness at the end of life.
AB  - CONTEXT: Patients or family members facing serious illness often express regrets
      over life events or the need for forgiveness. Professionals, including nurses as
      the prominent discipline at the bedside, witness these expressions of regret or
      needs for forgiveness but may not be adequately prepared to optimally address
      patient concerns regarding forgiveness. OBJECTIVES: The objectives of this
      descriptive study were to 1) identify contexts in which nurses have witnessed
      expressions of regret or the need for forgiveness and 2) describe nurses'
      responses to these clinical experiences related to forgiveness. METHODS: Nurses
      attending palliative care educational programs shared narratives of their
      experiences in caring for patients who expressed regret or the need for
      forgiveness. Study narratives were analyzed qualitatively, using content
      analysis. Themes were identified. RESULTS: Narratives were provided by 339 nurses
      from courses throughout the U.S. and Belize, India, the Philippines, and Romania.
      CONCLUSION: Nurses provide clinical care for patients with advanced illness who
      struggle with issues of forgiveness. Nurses would benefit from additional
      education regarding how best to address these concerns.

PMID- 23880587
TI  - Prognostication based on the change in the palliative prognostic index for
      patients with terminal cancer.
AB  - CONTEXT: The use of the Palliative Prognostic Index (PPI) in relation to the
      clinical time course has not yet been established. OBJECTIVES: To investigate the
      association between the changes in the PPI over time and the survival of terminal
      cancer patients in a palliative care unit (PCU). METHODS: This retrospective
      cohort study analyzed data from 374 terminal cancer patients who were admitted to
      the PCU of a university hospital in Japan. Clinical data, such as age, gender,
      body mass index, vital signs, initial PPI, and subsequent PPI, were collected
      from the medical records. The PPI change per day (DeltaPPI) was calculated using
      the initial PPI at admission and the one after five to seven days. The factors
      associated with death within three weeks were identified using Cox proportional
      hazards model analysis. RESULTS: After their admission to the PCU, 147 (39.3%)
      patients were deceased within three weeks. The multivariate-adjusted analysis
      showed that body temperature (hazard ratio [HR] 0.7; 95% CI 0.5, 1.0), initial
      PPI (HR 1.3; 95% CI 1.2, 1.4), and DeltaPPI (HR 6.6; 95% CI 4.9, 9.0) were
      significantly and independently associated with death within three weeks. In the
      subanalysis, the DeltaPPI was significantly associated with death within three
      weeks in the group with initial PPI <= 4 (HR 9.3; 95% CI 5.8, 15.0), 4 < initial
      PPI <= 6 (HR 14.4; 95% CI 5.7, 36.2), and initial PPI > 6 (HR 9.0; 95% CI 4.1,
      20.0). CONCLUSION: Our data suggest that the DeltaPPI may be useful for
      predicting the survival of terminally ill cancer patients.

PMID- 23880588
TI  - One, two, or three? Constructs of the brief pain inventory among patients with
      non-cancer pain in the outpatient setting.
AB  - CONTEXT: Either a two-factor representation (pain intensity and interference) or
      a three-factor representation (pain intensity, activity interference, and
      affective interference) of the modified Brief Pain Inventory (BPI) is appropriate
      among cancer patients. OBJECTIVES: To evaluate the extent to which a three-factor
      representation (pain intensity, activity interference, and affective
      interference) is appropriate for BPI among patients with noncancer pain seen in
      an outpatient setting. METHODS: We conducted a prospective, multicenter,
      observational, nonrandomized study using patient pain registry data from
      outpatient settings. Seven hundred forty-one patients with acute episodes of
      noncancer pain requiring treatment with a prescription medication containing
      oxycodone immediate-release on an as-needed basis for at least five days
      participated. Baseline measurements included the modified BPI pain intensity
      (right now, average, and worst in 24 hours) and pain interference with general
      activities, walking, work, mood, relations with others, sleep, and life
      enjoyment. Confirmatory factor analysis was conducted for the overall sample and
      among postoperative patients (n = 133), patients with back and neck pain (n =
      202), patients with arthritis (n = 148), and patients with injury or trauma (n =
      204). RESULTS: Both the two-factor and three-factor models were statistically
      better than the one-factor model (P < 0.05), with the two-factor model performing
      better than the three-factor model. Configural invariance, but not metric
      invariance by patient cohort group was demonstrated. CONCLUSION: Consistent with
      analyses among cancer patients, a two-factor representation of BPI is appropriate
      for noncancer patients seen in an ambulatory setting. This work lends additional
      support for the psychometric properties of BPI.

PMID- 23880589
TI  - Prospective longitudinal evaluation of a symptom cluster in breast cancer.
AB  - CONTEXT: Symptom cluster research expands cancer investigations beyond a focus on
      individual symptoms in isolation. OBJECTIVES: We conducted a prospective
      longitudinal study of sleep, fatigue, depression, anxiety, and perceived
      cognitive impairment in patients with breast cancer undergoing chemotherapy.
      METHODS: Patient-reported outcome measures were administered prior to
      chemotherapy, at Cycle 4 Day 1, and six months after initiating chemotherapy.
      Participants were divided into four groups and assigned a symptom cluster index
      (SCI) score based on the number/severity of symptoms reported at enrollment.
      RESULTS: Participants (N = 80) were mostly women (97.5%) with Stage II (69.0%)
      breast cancer, 29-71 years of age. Scores on all measures were moderately-highly
      correlated across all time points. There were time effects for all symptoms,
      except sleep quality (nonsignificant trend), with most symptoms worsening during
      chemotherapy, although anxiety improved. There were no significant group * time
      interactions; all four SCI groups showed a similar trajectory of symptoms over
      time. Worse performance status and quality of life were associated with higher
      SCI score over time. CONCLUSION: With the exception of anxiety, the coherence of
      the symptom cluster was supported by similar patterns of severity and change over
      time in these symptoms (trend for sleep quality). Participants with higher SCI
      scores prior to chemotherapy continued to experience greater symptom burden
      during and after chemotherapy. Early assessment and intervention addressing this
      symptom cluster (vs. individual symptoms) may have a greater impact on patient
      performance status and quality of life for patients with higher SCIs.

PMID- 23880590
TI  - Implementation strategies for collaborative primary care-mental health models.
AB  - PURPOSE OF REVIEW: Extensive research exists that collaborative primary care
      mental health models can improve care and outcomes for patients. These programs
      are currently being implemented throughout the United States and beyond. The
      purpose of this study is to review the literature and to generate an overview of
      strategies currently used to implement such models in daily practice. RECENT
      FINDINGS: Six overlapping strategies to implement collaborative primary care
      mental health models were described in 18 selected studies. We identified
      interactive educational strategies, quality improvement change processes,
      technological support tools, stakeholder engagement in the design and execution
      of implementation plans, organizational changes in terms of expanding the task of
      nurses and financial strategies such as additional collaboration fees and pay for
      performance incentives. SUMMARY: Considering the overwhelming evidence about the
      effectiveness of primary care-mental health models, there is a lack of good
      studies focusing on their implementation strategies. In practice, these
      strategies are multifaceted and locally defined, as a result of intensive and
      required stakeholder engagement. Although many barriers still exist, the
      implementation of collaborative models could have a chance to succeed in the
      United States, where new service delivery and payment models, such as the Patient
      Centered Medical Home, the Health Home and the Accountable Care Organization, are
      being promoted.

PMID- 23880591
TI  - The portrait of the psychiatrist as a globally minded citizen.
AB  - PURPOSE OF REVIEW: To discuss the importance of psychopathology in psychiatric
      curricula. RECENT FINDINGS: 2013 is the centennial of the first edition of Karl
      Jaspers' General Psychopathology. Several books and articles published during
      this year discuss the role of psychopathology for psychiatrists. SUMMARY:
      Psychiatrists need personal formation or cultivation alongside a thorough
      scientific education - restrictively understood as acquisition of technical
      knowledge and skill training. Psychopathology provides both educational resources
      (e.g., valid and reliable concepts and methods for establishing accurate
      diagnosis) and that kind of sensitivity, namely the sensitivity to what is
      appropriate in dealing with others, for which knowledge from general principles
      does not suffice. Tact, as the ability to feel an atmosphere and to attune with
      it in those situations that are not yet plainly and unambiguously defined, is an
      example of this. When evidence-based guidelines are still scarce (as is the case,
      for instance, with early psychoses), tact seems to be an indispensable resource
      for the psychiatrist.

PMID- 23880592
TI  - Medication nonadherence and psychiatry.
AB  - PURPOSE OF REVIEW: Nonadherence to appropriately prescribed medication for
      psychiatric disorders prevents patients from realizing the full benefits of their
      treatment and negatively impacts on individuals, their families and the
      healthcare system. Understanding and reducing nonadherence is therefore a key
      challenge to quality care for patients with psychiatric disorders. This review
      highlights findings regarding the prevalence and consequence of nonadherence,
      barriers to adherence and new intervention methods from 2012 onwards. RECENT
      FINDINGS: Recent research has highlighted that nonadherence is a global challenge
      for psychiatry and has linked nonadherence to poorer outcomes, including hospital
      admissions, suicide and mortality. Optimizing medication regimens can reduce
      nonadherence; however, often a complex interplay of factors affects individuals'
      motivation and ability to follow their prescription. Psychiatrists can enable
      patients to develop an accurate model of their illness and treatment and
      facilitate adherence. However, nonadherence is often a hidden issue within
      consultations. Novel interventions using new technologies and tailoring
      techniques may have the potential to reduce nonadherence. SUMMARY: Nonadherence
      remains a significant challenge for patients with psychiatric disorders,
      physicians and healthcare systems. New developments demonstrate the importance of
      developing tailored interventions to enable patients to overcome perceptual and
      practical barriers to adherence.

PMID- 23880593
TI  - Could intranasal oxytocin be used to enhance relationships? Research imperatives,
      clinical policy, and ethical considerations.
AB  - PURPOSE OF REVIEW: Well-functioning romantic relationships are important for long
      term health and well being, but they are often difficult to sustain. This
      difficulty arises (in part) because of an underlying tension between our
      psychobiological natures, culture/environment, and modern love and relationship
      goals. One possible solution to this predicament is to intervene at the level of
      psychobiology, enhancing partners' interpersonal connection through neurochemical
      modulation. This article focuses on a single, promising biobehavioral sub-system
      for such intervention: the attachment system, based largely upon the expression
      of the neuropeptide oxytocin. Could the exogenous administration of oxytocin -
      under the right conditions - be used to facilitate relational or marital well
      being? RECENT FINDINGS: If so, it would require considerable forethought. Recent
      research complicates the popular image of oxytocin as a universal social enhancer
      or 'love hormone' and shows that it may exert a variety of different effects, at
      different dosages, on different people, under different circumstances.
      Accordingly, we discuss what is known about oxytocin, including its 'good' and
      'bad' effects on human behavior and on higher-order functional processes.
      SUMMARY: Building upon animal-model, human preclinical, and clinical findings, we
      outline a proposal for the use of oxytocin in the therapeutic neuroenhancement of
      contemporary romantic relationships. Highlighting key targets for future research
      along the way, we then conclude by discussing some of the clinical and ethical
      considerations that would pertain to the implementation of this knowledge in
      applied settings.

PMID- 23880594
TI  - Avoidance of weight gain is important for oral type 2 diabetes treatments in
      Sweden and Germany: patient preferences.
AB  - AIMS: The aim of the study was to quantify patient preferences for outcomes
      associated with oral antidiabetic medications (OAMs) in Sweden and Germany
      through a discrete-choice experiment. METHODS: Adults taking OAMs who had a self
      reported physician's diagnosis of type 2 diabetes mellitus (T2DM) made a series
      of nine choices between pairs of hypothetical profiles. Each profile had a
      predefined range of attributes: blood glucose control, frequency of mild-to
      moderate hypoglycaemia, annual severe hypoglycaemic events, annual weight gain,
      pill burden and frequency of administration, and cost. Choice questions were
      based on an experimental design with known statistical properties. Bivariate
      probit analysis estimated the probabilities of choice of medication
      administration from patient characteristics and, conditional on that choice,
      preferences for treatment outcomes. RESULTS: The final sample consisted of 188
      Swedish and 195 German patients. For both countries, weight gain was the most
      important attribute, followed by blood glucose control. Avoiding a 5-kg weight
      gain was 1.5 times more important in Sweden and 2.3 times more important in
      Germany than achieving moderate blood glucose control, thereby, suggesting that
      blood glucose control is relatively more important to Swedish than to German
      patients. Least important outcomes were the number of daily pills (Sweden) and
      frequency of mild-to-moderate hypoglycaemia (Germany). CONCLUSION: Patients in
      both Sweden and Germany preferred OAMs not associated with weight gain.

PMID- 23880595
TI  - Are dopamine D2 receptors out of control in psychosis?
AB  - It is known that schizophrenia patients are behaviorally supersensitive to
      dopamine-like drugs (amphetamine, methylphenidate). There is evidence for an
      increased release of dopamine, a slight increase of dopamine D2 receptors and an
      increase of dopamine D2High receptors in schizophrenia, all possibly explaining
      the clinical supersensitivity to dopamine. The elevation in apparent D2High
      receptors in vivo in schizophrenia matches the elevation in D2High receptors in
      many animal models of psychosis. The increased amounts of D2High receptors in
      psychotic-like behavior in animals may result from a loss of control of D2 by
      various factors. These factors include the rate of phosphorylation and
      desensitization of D2 receptors by kinases, the attachment of arrestin to D2
      receptors, internalization of D2 receptors, the rate of receptor de
      phosphorylation, formation of D2 receptor dimers, and GTP regulation by various
      GTPases. While at present there are no statistically significant associations of
      any of these controlling factors and their genes with schizophrenia,
      investigation of D2High receptors in schizophrenia will require a new radioligand
      in order to selectively label D2High receptors in vivo in patients. Finally,
      haloperidol reduces the number of D2High receptors that are elevated by
      amphetamine, indicating that this therapeutic effect may occur clinically. 

PMID- 23880596
TI  - Novel NLRP7 mutations in familial recurrent hydatidiform mole: are NLRP7
      mutations a risk for recurrent reproductive wastage?
AB  - OBJECTIVE: Familial recurrent hydatidiform mole is an exceedingly rare clinical
      condition. Affected women are predisposed to molar pregnancies of diploid,
      biparental origin rather than androgenetic origin. At present, NLRP7 and KHDC3L
      (C6orf221) are the only genes known to be associated with familial recurrent
      hydatidiform mole. This study investigated the genetic dispositions in two large
      Turkish families with recurring molar conceptuses. STUDY DESIGN: Copy number
      variation analysis was performed followed by NLRP7 gene sequencing. The finding
      of a mono-allelic condition in one family led to investigation of the adjacent
      NLRP2 gene and recently associated KHDC3L gene. Sampled molar tissues were
      genotyped using microsatellite markers. RESULTS: In one family, a homozygous
      single nucleotide insertion that caused a frameshift leading to an early stop
      codon, c.2940_2941insC (p.Glu981ArgfsX13), was identified in the affected
      sisters. In the other family, a heterozygous 60-kb deletion eliminating
      substantial portions of the NLRP2 and NLRP7 genes on one allele was found.
      Screening of NLRP2 and KHDC3L genes revealed no alterations that were considered
      to be pathological. Genotyping of six independent molar conceptions revealed that
      five were of diploid, biparental origin and one was of diandric, triploid origin.
      CONCLUSIONS: Two novel protein-truncating mutations in the NLRP7 gene were found
      to be associated with familial recurrent hydatidiform mole. Mutations in the
      NLRP7 gene causing recurrent biparental hydatidiform mole may also be associated
      with other forms of recurrent reproductive wastage.

PMID- 23880597
TI  - Opportunistic and interventional salpingectomy in women at risk: a strategy for
      preventing pelvic serous cancer (PSC).
AB  - OBJECTIVE: Salpingectomy is proposed as a prophylactic measure to reduce the
      incidence of tubo-ovarian/pelvic serous cancers. We surveyed the attitudes of
      obstetrician/gynecologists to incorporating salpingectomy opportunistically into
      surgery for benign conditions, and electively for young BRCA mutation carriers.
      STUDY DESIGN: A questionnaire, designed to assess current standard clinical
      practice and willingness to perform salpingectomy for female sterilization at
      abdominal hysterectomy for benign disease (ABH), vaginal benign hysterectomy
      (VBH) and electively for women with BRCA mutations who wish to postpone
      oophorectomy was mailed to obstetrician/gynecologists working in Irish hospitals.
      RESULTS: In their current practice of interval female sterilization 96% of
      gynecologists applied clips at laparoscopy and 4% performed salpingectomy, and
      73% were willing to consider salpingectomy. Eighty-one percent were willing to
      consider salpingectomy for sterilization at cesarean section. Gynecologists
      performing hysterectomy (without oophorectomy) for benign conditions did
      salpingectomy in 26% at ABH and 5.4% at VBH, and now 90% would consider
      salpingectomy at ABH and 66% at VBH. Two-thirds of respondents would consider
      salpingectomy for women at genetic risk of ovarian cancer who want to postpone
      oophorectomy. CONCLUSION: Changing general gynecological practice to include more
      opportunistic salpingectomy has the potential to reduce the incidence of serous
      cancers. The majority of gynecologists are willing to incorporate more
      salpingectomies into their surgical practices and consider elective salpingectomy
      as an interim measure for women with defined genetic risk of pelvic serous
      cancer.

PMID- 23880598
TI  - A phase II study of combination chemotherapy using docetaxel and irinotecan for
      TC-refractory or TC-resistant ovarian carcinomas (GOGO-OV2 study) and for primary
      clear or mucinous ovarian carcinomas (GOGO-OV3 Study).
AB  - OBJECTIVE: To analyze the efficacy and safety of combination chemotherapy of
      docetaxel and irinotecan for paclitaxel and carboplatin (TC) -refractory or 
      resistant ovarian carcinomas and for first treatment of primary clear cell and
      mucinous ovarian carcinomas. STUDY DESIGN: Between 2002 and 2009, we conducted a
      prospective Phase II study of the efficacy and safety of combination chemotherapy
      using docetaxel and irinotecan in 62 patients with TC-refractory or -resistant
      ovarian carcinoma cases (GOGO-OV2) and 15 patients with primary clear cell and
      mucinous ovarian carcinoma cases (GOGO-OV3). The dose of docetaxel and irinotecan
      was determined during our previous Phase I study. RESULTS: A docetaxel plus
      irinotecan regimen provided a 53% response rate, 6 months progression-free
      survival (PFS), and 12 months overall survival (OS) for primary clear cell and
      mucinous ovarian carcinomas (similar to TC therapy). The differences of anti
      tumor and survival effects between refractory and resistant cases were not
      statistically significant. The regimen also provided a 15% response rate, 5
      months PFS, and 15 months OS for TC-refractory or TC-resistant cases, when used
      as a second-line chemotherapy. These data are similar to previous reports,
      however, our study provides the first data exclusively for the cases refractory
      or resistant to a gold standard TC therapy as a second-line chemotherapy. The
      regimen was demonstrated to be well tolerable. CONCLUSION: Combination
      chemotherapy of docetaxel and irinotecan may be a useful option to treat TC
      refractory/resistant cases and primary clear cell and mucinous adenocarcinoma
      cases of ovarian carcinoma.

PMID- 23880599
TI  - Blockade of endothelin receptors with bosentan limits ischaemia/reperfusion
      induced injury in rat ovaries.
AB  - OBJECTIVE: To investigate the role of endothelin receptors in ovarian
      ischaemia/reperfusion (I/R) injury in rats using the endothelin receptor
      antagonist bosentan. STUDY DESIGN: Group 1: sham operation; Group 2: sham
      operation and bosentan 60 mg/kg; Group 3: bilateral ovarian ischaemia; Group 4: 3
      h period of ischaemia followed by 3h of reperfusion; Groups 5 and 6: bosentan 30
      and 60 mg/kg, respectively, with bilateral ovarian ischaemia applied 30 min
      later; the bilateral ovaries were removed after 3h of ischaemia; Groups 7 and 8:
      3h of bilateral ovarian ischaemia was applied, with bosentan 30 and 60 mg/kg,
      respectively, administered 2.5h after the induction of ischaemia; following the 3
      h period of ischaemia, 3h of reperfusion was applied, after which the ovaries
      were removed. RESULTS: Ischaemia and I/R decreased superoxide dismutase (SOD)
      activity and the level of glutathione (GSH) in ovarian tissue, but increased the
      level of malondialdehyde (MDA) significantly compared with the sham operation
      group. Bosentan 30 and 60 mg/kg before ischaemia and I/R decreased the MDA level
      and increased SOD activity and the GSH level in the experimental groups. The
      serum levels of the inflammatory cytokines interleukin (IL)-1beta, IL-6 and
      tumour necrosis factor-alpha were also measured in the I/R injury model in rat
      ovaries. The levels of these cytokines were significantly higher in the ischaemia
      and I/R groups compared with the sham operation and sham operation plus bosentan
      groups. The histopathological findings also demonstrated the protective role of
      bosentan against I/R-induced injury in rat ovaries. CONCLUSION: Administration of
      bosentan protects the ovaries against oxidative damage and I/R-induced injury.

PMID- 23880600
TI  - A questionnaire assessing women's care needs related to gynaecological cancer
      screening: development of the GCSCNS.
AB  - OBJECTIVE: To identify women's care needs concerning cancer screening and to
      develop an instrument suitable for measuring them--the Gynaecological Cancer
      Screening Care Needs Scale (GCSCNS). We hypothesized that it is possible: (a) to
      explore care needs and to develop reliable subscales of them, (b) to rank these
      needs in order of importance, and (c) to detect determinants of these needs (age,
      social status, marital status, health locus of control) and these need scores.
      STUDY DESIGN: A questionnaire was developed based on the relevant literature,
      interviews conducted with gynaecological patients, and a consultation with 18
      experts. The questionnaire listed 58 items addressed to physicians which deal
      with information and support needs during gynaecological cancer screening.
      Subjects rated the importance of each item using a five-point scale (from 1=very
      important, to 5=not important). The questionnaire also asked for patients'
      demographic information and their locus of control. It was distributed to 1000
      female patients in 10 gynaecological practices in 3 federal states of Germany as
      an exploratory multi-centric cross-sectional study. A total of 961 women
      completed the questionnaire. Descriptive statistics were used to analyze
      patients' demographic variables. With a principal component analysis (PCA,
      Varimax rotation), three care needs subscales were generated which then led to
      the GCSCNS scales. RESULTS: The dimensions of patients' care needs can be
      described on three subscales: "Need for Information" (GCSCNS-I), "Need for
      Respect and Empathy during the physical examination" (GCSCNS-RE), "Need for
      Caring and Availability of the doctor" (GCSCNS-CA). Internal consistencies varied
      between good and very good (Cronbach's alpha .80-.89). Data indicate that it is
      possible to rank the female care needs in order of importance and that they are
      dependent on age and social status, but not on marital status and locus of
      control regarding health and disease. CONCLUSION: Because there is no comparable
      research available on this topic, we developed an instrument for measuring female
      care needs related to gynaecological cancer screening. The results give
      gynaecologists the opportunity to better fulfil their patients' wishes and needs
      and perhaps increase participation in gynaecological cancer screening.

PMID- 23880601
TI  - Associations between retrospective versus ecological momentary assessment
      measures of emotion and eating disorder symptoms in anorexia nervosa.
AB  - This study examined the unique associations between eating disorder symptoms and
      two emotion-related constructs (affective lability and anxiousness) assessed via
      distinct methodologies in anorexia nervosa (AN). Women (N = 116) with full or
      subthreshold AN completed baseline emotion and eating disorder assessments,
      followed by two weeks of ecological momentary assessment (EMA). Hierarchical
      regressions were used to examine unique contributions of baseline and EMA
      measures of affective lability and anxiousness in accounting for variance in
      baseline eating disorder symptoms and EMA dietary restriction, controlling for
      age, body mass index, depression, and AN diagnostic subtype. Only EMA affective
      lability was uniquely associated with baseline eating disorder symptoms and EMA
      dietary restriction. Anxiousness was uniquely associated with baseline eating
      disorder symptoms regardless of assessment method; neither of the anxiousness
      measures was uniquely associated with EMA dietary restriction. Affective lability
      and anxiousness account for variance in global eating disorder symptomatology; AN
      treatments targeting these emotion-related constructs may prove useful.

PMID- 23880602
TI  - Higher methadone doses are associated with lower mortality in patients of opioid
      dependence in Taiwan.
AB  - Optimal methadone dosage and service profile is challenging in treatment of
      opioid dependence. This study explores the impact of methadone dosage on the
      mortality of opioid-dependent patients in methadone maintenance therapy by using
      a large-scale and continual supervised dosing registry information system.
      Database of nationwide enrolled opioid-dependent patients at methadone clinics in
      Taiwan during 2006-2008 was assessed. The relative risk of age, sex, marital
      status, HIV infection and methadone dosage were analyzed by Cox regression
      analysis. Among all of the 33,549 recruited patients, the crude mortality rate
      was 134.78/10,000 person-years, and the standardized mortality ratio was 4.68. A
      dose-response relationship of higher- vs. lower-dosage groups on the risk of
      mortality risk was observed (adjusted HR = 0.68, P = 0.016). In further sub
      grouping analysis, this trend was more significant in HIV positive patients, in
      subgroup of patients who continuously staying in MMT, and in subgroup of patients
      who re-enter MMT. This dosage effect is not significantly seen in patients
      receiving MMT more than 365 days. Further exploration of other treatment-related
      factors may be important for understanding the long-term treatment outcome of
      opioid addiction patients.

PMID- 23880603
TI  - Impact tolerance in mussel thread networks by heterogeneous material
      distribution.
AB  - The Mytilidae, generally known as marine mussels, are known to attach to most
      substrates including stone, wood, concrete and iron by using a network of byssus
      threads. Mussels are subjected to severe mechanical impacts caused by waves.
      However, how the network of byssus threads keeps the mussel attached in this
      challenging mechanical environment is puzzling, as the dynamical forces far
      exceed the measured strength of byssus threads and their attachment to the
      environment. Here we combine experiment and simulation, and show that the
      heterogeneous material distribution in byssus threads has a critical role in
      decreasing the effect of impact loading. We find that a combination of stiff and
      soft materials at an 80:20 ratio enables mussels to rapidly and effectively
      dissipate impact energy. Notably, this facilitates a significantly enhanced
      strength under dynamical loading over 900% that of the strength under static
      loading. 

PMID- 23880604
TI  - Highlights in advanced prostate cancer from the 2013 American Society of Clinical
      Oncology Genitourinary Cancers Symposium.

PMID- 23880606
TI  - Cross-linked glucose oxidase clusters for biofuel cell anode catalysts.
AB  - The efficient localization of increased levels of active enzymes onto conducting
      scaffolds is important for the development of enzyme-based biofuel cells. Cross
      linked enzyme clusters (CEC) of glucose oxidase (GOx) constrained to
      functionalized carbon nanotubes (CEC-CNTs) were generated in order to evaluate
      the potential of using CECs for developing GOx-based bioanodes functioning via
      direct electron transfer from the GOx active site to the CNT scaffold. CEC-CNTs
      generated from several weight-to-weight ratios of GOx:CNT were examined for
      comparable catalytic activity to free GOx into the solution, with CEC-CNTs
      generated from a 100% GOx solution displaying the greatest enzymatic activity.
      Scanning transmission electron microscopic analysis of CEC-CNTs generated from
      100% GOx to CNT (wt/wt) ratios revealed that CEC clusters of ~78 um2 localized to
      the CNT surface. Electrochemical analysis indicates that the enzyme is engaged in
      direct electron transfer, and biofuel cells generated using GOx CEC-CNT bioanodes
      were observed to have a peak power density of ~180 uW cm(-2). These data indicate
      that the generation of nano-to-micro-sized active enzyme clusters is an
      attractive option for the design of enzyme-specific biofuel cell powered
      implantable devices.

PMID- 23880607
TI  - Development and characterization of a novel fluorescent indicator protein PMCA4
      GCaMP2 in cardiomyocytes.
AB  - Isoform 4 of the plasma membrane calcium/calmodulin dependent ATPase (PMCA4) has
      recently emerged as an important regulator of several key pathophysiological
      processes in the heart, such as contractility and hypertrophy. However, direct
      monitoring of PMCA4 activity and assessment of calcium dynamics in its vicinity
      in cardiomyocytes are difficult due to the lack of molecular tools. In this
      study, we developed novel calcium fluorescent indicators by fusing the GCaMP2
      calcium sensor to the N-terminus of PMCA4 to generate the PMCA4-GCaMP2 fusion
      molecule. We also identified a novel specific inhibitor of PMCA4, which might be
      useful for studying the role of this molecule in cardiomyocytes and other cell
      types. Using an adenoviral system we successfully expressed PMCA4-GCaMP2 in both
      neonatal and adult rat cardiomyocytes. This fusion molecule was correctly
      targeted to the plasma membrane and co-localised with caveolin-3. It could
      monitor signal oscillations in electrically stimulated cardiomyocytes. The PMCA4
      GCaMP2 generated a higher signal amplitude and faster signal decay rate compared
      to a mutant inactive PMCA4(mut)GCaMP2 fusion protein, in electrically stimulated
      neonatal and adult rat cardiomyocytes. A small molecule library screen enabled us
      to identify a novel selective inhibitor for PMCA4, which we found to reduce
      signal amplitude of PMCA4-GCaMP2 and prolong the time of signal decay (Tau) to a
      level comparable with the signal generated by PMCA4(mut)GCaMP2. In addition,
      PMCA4-GCaMP2 but not the mutant form produced an enhanced signal in response to
      beta-adrenergic stimulation. Together, the PMCA4-GCaMP2 and PMCA4(mut)GCaMP2
      demonstrate calcium dynamics in the vicinity of the pump under active or inactive
      conditions, respectively. In summary, the PMCA4-GCaMP2 together with the novel
      specific inhibitor provides new means with which to monitor calcium dynamics in
      the vicinity of a calcium transporter in cardiomyocytes and may become a useful
      tool to further study the biological functions of PMCA4. In addition, similar
      approaches could be useful for studying the activity of other calcium
      transporters during excitation-contraction coupling in the heart. 

PMID- 23880608
TI  - Effect of SR load and pH regulatory mechanisms on stretch-dependent Ca(2+) entry
      during the slow force response.
AB  - When cardiac muscle is stretched, there is an initial inotropic response that
      coincides with the stretch followed by a slower increase in twitch force that
      develops over several minutes (the "slow force response", or SFR). Unlike the
      initial response to stretch, the SFR is produced by an increase in Ca(2+)
      transient amplitude, but the cellular mechanisms that give rise to the increased
      transients are still debated. We have examined the relationship between the SFR,
      intracellular [Ca(2+)] and the inotropic state of right ventricular trabeculae
      from rat hearts at 37 degrees C. The magnitude of the SFR varied with [Ca(2+)]o
      and stimulation frequency, so that the SFR was greatest for conditions associated
      with a reduced SR Ca(2+) content. The SFR was not blocked by the AT1 receptor
      blocker losartan, but was reduced by SN-6, an inhibitor of reverse mode
      Na(+)/Ca(2+)-exchange (NCX). The Na(+)/H(+)-exchange (NHE) inhibitor HOE642 had
      no effect in HCO3(-)-buffered solutions, but blocked 50% of the SFR in HCO3(-)
      free solution. Inhibition of HCO3(-) transport by DIDS increased the SFR and made
      it sensitive to HOE642. The addition of cross-bridge cycle inhibitors (20mM BDM
      or 20MUM blebbistatin) to the superfusate reduced the SFR as monitored by changes
      in Ca(2+). In HCO3(-)-free conditions, the SFR was associated with a slow
      acidification that was inhibited by BDM, and by stopping electrical stimulation.
      These results can be explained by stretch increasing metabolic demand and
      stimulating Na(+) entry via both NHE and the Na(+)/HCO3(-) transporters. This
      mechanism provides a novel link between inotropic state and stretch, as well as a
      way for the cell to compensate for increased acid load. The feedback mechanism
      between force and Ca(2+) transient amplitude that we describe is also limited by
      the degree of SR Ca(2+) load. 

PMID- 23880609
TI  - Human plasminogen kringle 1-5 inhibits angiogenesis and induces thrombomodulin
      degradation in a protein kinase A-dependent manner.
AB  - Kringle 1-5 (K1-5), an endogenous proteolytic fragment of human plasminogen
      (Plg), is an angiostatin-related protein that inhibits angiogenesis. Many
      angiostatin-related proteins have been identified, but the detailed molecular
      mechanisms underlying their antiangiogenic effects remain unclear. Thrombomodulin
      (TM) is a transmembrane glycoprotein that plays a major role in the
      anticoagulation process in endothelial cells. Previously, we demonstrated that
      recombinant TM could interact with Plg to enhance Plg activation. In the present
      study, we investigated the interaction between TM and K1-5, and their functions
      in endothelial cells. We found that K1-5 colocalized with TM and directly
      interacted with TM through the TM lectin-like domain. After K1-5 interacted with
      TM, it induced TM internalization and degradation. In addition, the K1-5-induced
      TM internalization and degradation in proteasomes after ubiquitin modification
      were dependent on protein kinase A (PKA). Moreover, a PKA-specific inhibitor
      reversed the effects of K1-5 on cell migration and tube formation. Consistent
      with these findings, TM overexpression resulted in increased cell migration;
      moreover, K1-5 inhibited the increase of TM-mediated cell migration in a PKA
      dependent manner. We determined that TM acts as a K1-5 receptor and that K1-5
      induces TM internalization, ubiquitination, and degradation through the PKA
      pathway, by which K1-5 may inhibit endothelial cell migration and tube formation.

PMID- 23880610
TI  - PKCepsilon activation promotes FGF-2 exocytosis and induces endothelial cell
      proliferation and sprouting.
AB  - Protein kinase C epsilon (PKCepsilon) activation controls fibroblast growth
      factor-2 (FGF-2) angiogenic signaling. Here, we examined the effect of activating
      PKCepsilon on FGF-2 dependent vascular growth and endothelial activation.
      psiepsilonRACK, a selective PKCepsilon agonist induces pro-angiogenic responses
      in endothelial cells, including formation of capillary like structures and cell
      growth. These effects are mediated by FGF-2 export to the cell membrane, as
      documented by biotinylation and immunofluorescence, and FGF-2/FGFR1 signaling
      activation, as attested by ERK1/2-STAT-3 phosphorylation and de novo FGF-2
      synthesis. Similarly, vascular endothelial growth factor (VEGF) activates
      PKCepsilon in endothelial cells, and promotes FGF-2 export and FGF-2/FGFR1
      signaling activation. psiepsilonRACK fails to elicit responses in FGF-2(-/-)
      endothelial cells, and in cells pretreated with methylamine (MeNH2), an
      exocytosis inhibitor, indicating that both intracellular FGF-2 and its export
      toward the membrane are required for the psiepsilonRACK activity. In vivo
      psiepsilonRACK does not induce angiogenesis in the rabbit cornea. However,
      psiepsilonRACK promotes VEGF angiogenic responses, an effect sustained by
      endothelial FGF-2 release and synthesis, since anti-FGF-2 antibody strongly
      attenuates VEGF responses. The results demonstrate that PKCepsilon stimulation
      promotes angiogenesis and modulates VEGF activity, by inducing FGF-2 release and
      autocrine signaling. 

PMID- 23880611
TI  - Upregulation of CD11b on eosinophils in aspirin induced asthma.
AB  - BACKGROUND: Although a challenge test using non-steroidal anti-inflammatory drugs
      (NSAIDs) is crucial for diagnosis of aspirin-induced asthma (AIA), it also has
      drawbacks in terms of possible side effects. Therefore, alternative in-vitro
      diagnostic methods for AIA are awaited. METHODS: Nineteen stable non-AIA patients
      (9 males and 10 females; mean age, 49.4 +/- 4.8 years), and 20 AIA patients (9
      males and 11 females; mean age, 51.1 +/- 4.8 years) were enrolled in this study.
      CD11b and CD16 expressions on the peripheral-blood granulocytes after
      administration of aspirin and different concentrations of PGE2 in vitro were
      examined using flowcytometry. RESULTS: Aspirin induced a significant increase in
      CD11b expression on eosinophils (CD16 negative granulocytes) in 19 AIA patients
      and one non-AIA patient. Increase in CD11b expression on eosinophils by aspirin
      administration was suppressed by PGE2 in a dose-dependent manner. CONCLUSIONS:
      The measurement of CD11b expression on peripheral-blood eosinophils showed very
      high sensitivity and specificity of (-95%) in diagnosing AIA. Although this
      method requires laboratory facilities for flowcytometry, it may be very useful in
      diagnosis of AIA without side effects. In addition, PGE2 may be involved in
      regulation of CD11b expression on eosinophils by aspirin administration.

PMID- 23880612
TI  - Predictors for identifying the efficacy of systemic steroids on sustained exhaled
      nitric oxide elevation in severe asthma.
AB  - BACKGROUND: Some patients with asthma have high levels of exhaled nitric oxide
      fraction (FENO) despite inhaled corticosteroids (ICS) therapy. Early studies
      suggested that this might be explained by the presence of heterogeneous airway
      inflammation. We aimed to assess the predictors for identifying the efficacy of
      systemic corticosteroids on residual FENO elevations in severe asthma. METHODS:
      Twenty severe asthmatics with persistent FENO elevation (>=40ppb) despite
      maintenance therapy including high-daily-dose ICS were enrolled. Asthma Control
      Questionnaire (ACQ), lung function, blood eosinophils, and FENO were assessed
      before and after 14 days treatment with 0.5mg/kg oral prednisolone/day. RESULTS:
      ACQ, blood eosinophils, FENO level, FVC, FEV1, FEV1/FVC ratio and the slope of
      the single nitrogen washout curve (DeltaN2) were significantly improved by
      treatment with prednisolone. 70% of the subjects showed >=20% reductions in the
      FENO levels. The reduction in FENO levels was significantly correlated with the
      improvements in ACQ (p < 0.0001), FVC (p < 0.01), FEV1 (p < 0.0001), and DeltaN2
      (p < 0.05). Among the measurements at baseline, the FENO levels and blood
      eosinophil numbers were identified as significant predictors of >=20% reductions
      in the FENO levels by systemic steroid therapy. CONCLUSIONS: Systemic
      corticosteroids could suppress the residual FENO elevations in more than half of
      the patients with severe asthma and the reduction in FENO levels was associated
      with improvements in asthma control and airflow limitation. The FENO levels and
      blood eosinophil numbers were the predictors of improved residual airway
      inflammation by systemic steroid therapy in severe asthma.

PMID- 23880613
TI  - Occupational airborne contact dermatitis by isothiazolinones contained in wall
      paint products.

PMID- 23880614
TI  - Bird fancier's lung caused by diamond dove.

PMID- 23880615
TI  - Correlation between soluble interleukin-2 receptor levels and modified Rodnan
      total skin thickness scores in a patient with generalized morphea: a case report.

PMID- 23880616
TI  - Stratifying a risk for an increased variation of airway caliber among the
      clinically stable asthma.
AB  - BACKGROUND: Recently, correlations of peak expiratory flow (PEF) variation have
      been shown to facilitate the prediction of later asthma symptoms and
      exacerbations. However, it has not been fully examined whether or not any patient
      characteristics are associated with the residual airway lability in treated
      asthmatics. The objective of this study is to examine a predictive marker for
      increased variation of PEF in patients with clinically stable asthma. METHODS: We
      studied 297 asthmatic patients who were monitored for PEF twice a day. Asthma
      Control Questionnaire (ACQ), spirometry, and exhaled nitric oxide fraction (FENO)
      were measured. After the assessment of baseline values, PEF measuring was
      continued and associations between these clinical markers and later variation of
      PEF over a week (Min%Max) were investigated. RESULTS: 17.5% of the subjects
      showed increased PEF variability (Min%Max < 80%). ACQ, forced expiratory volume
      in 1 s % of predicted (%FEV1), and FENO were identified as independent predictors
      of Min%Max < 80%. An ACQ >= 0.4 yielded 96% sensitivity and 59% specificity, a
      %FEV1 <= 85% yielded 62% sensitivity and 89% specificity, and a FENO >= 40 ppb
      yielded 75% sensitivity and 90% specificity for identifying the subjects with
      high variability in PEF. When we combine %FEV1 <= 85% and FENO >= 40 ppb, this
      index showed the highest specificity (98%) for increased PEF variability.
      CONCLUSIONS: These results indicate that ACQ, %FEV1 and FENO can stratify the
      risk for increased variation in airway caliber among patients with stable asthma.
      This may help identify subjects in whom further monitoring of lung function
      fluctuations is indicated.

PMID- 23880617
TI  - The sensitivity and clinical course of patients with wheat-dependent exercise
      induced anaphylaxis sensitized to hydrolyzed wheat protein in facial soap -
      secondary publication.
AB  - BACKGROUND: Recently, an increasing number of patients with wheat-dependent
      exercise-induced anaphylaxis (WDEIA) have been reported in Japan. Most of them
      had developed this condition during or after using hydrolyzed wheat protein (HWP)
      containing soap (HWP-WDEIA). METHODS: To clarify the relation between WDEIA and
      HWP-containing soap and their prognosis, we retrospectively studied the patients
      who visited Hiroshima University Hospital and were diagnosed as WDEIA from
      January 2010 to June 2011. We took detailed clinical histories, performed skin
      prick tests, serum immunoassays for antigen-specific IgE and basophil histamine
      release test, and followed up their clinical courses after the diagnosis.
      RESULTS: Among 36 patients with WDEIA, 30 patients had used only one type of HWP
      soap. The patients with HWP-WDEIA were mainly women and had developed facial
      symptoms and angioedema. They suffered from blood pressure reductions less
      frequently than patients with conventional WDEIA. The levels of gluten-specific
      IgE were higher than those of omega-5 gliadin in patients with HWP-WDEIA (P <
      0.05, One-way ANOVA). All patients with HWP-WDEIA were positive against HWP in
      histamine release test. Among the conventional wheat antigens, glutenins induced
      the highest histamine release from basophils of patients with HWP-WDEIA. The
      sensitivities of patients against glutens and glutenins were reduced over months
      along with the discontinuance of HWP-soap. CONCLUSIONS: The development of HWP
      WDEIA is associated with the use of HWP-soap. The sensitivity to HWP that cross
      reacts with non-processed wheat may be reduced or possibly cured after the
      discontinuation of HWP-soap.

PMID- 23880618
TI  - There appears to be a discrepancy in the units of measurement in the article by
      Cordova and Cordova on their proposed new formula for LDL-cholesterol estimation.

PMID- 23880619
TI  - Biochemical effects of moderate dose vitamin A supplementation - How do we
      monitor vitamin A status?

PMID- 23880620
TI  - A combined laboratory and field evaluation of the Cholestech LDX and CardioChek
      PA point-of-care testing lipid and glucose analysers.
AB  - BACKGROUND: Combined lipid and glucose point-of-care testing (POCT) devices could
      facilitate widespread population screening for cardiovascular disease (CVD) and
      diabetes as part of the NHS Vascular Risk Assessment and Management Program (NHS
      Health Checks). An evaluation of the Cholestech LDX and CardioChek PA POCT
      analysers was performed in collaboration with the Wolverhampton City Primary Care
      Trust (PCT). METHODS: Intra-/inter-batch imprecision, between-analyser variation
      and the effect of haematocrit and ascorbic acid assay interference were
      investigated. Accuracy of the POCT capillary whole blood total cholesterol (TC),
      high-density-lipoprotein cholesterol (HDL-C) and glucose measurements was
      estimated by comparison with those from the laboratory analysis of paired venous
      samples. POCT usability and clinical governance were also assessed. RESULTS: The
      LDX exhibited lower intra- and inter-batch imprecision and external quality
      assessment (EQA) scheme between-analyser variation for the measurement of TC, HDL
      C and glucose when compared to the CardioChek. Ascorbic acid negatively
      interfered in all three assays on both POCT analysers and results reported by the
      CardioChek were influenced by the specimen haematocrit. The LDX displayed closer
      agreement with the laboratory methods for the measurement of TC and HDL-C but
      both the LDX and the CardioChek displayed positive bias for the measurement of
      glucose. CONCLUSIONS: POCT has clear advantages for delivering NHS Health Checks
      over the laboratory-based approach although device performance does differ. Users
      should also be aware of the potential clinical governance and interference issues
      associated with these devices.

PMID- 23880621
TI  - An association between body mass index and high-sensitivity C-reactive protein
      concentrations is influenced by age in community-dwelling persons.
AB  - BACKGROUND: High sensitivity C-reactive protein (hsCRP) is an acute phase
      reactant and a sensitive marker of inflammation. Age and adiposity can
      potentially promote the production of C-reactive protein (CRP). However, only a
      few studies have investigated any interaction between age and adiposity on hsCRP
      concentrations. METHODS: We recruited 822 men (mean age, 61 +/- 14 years) and
      1097 women (63 +/- 12 years) during their annual health examination from a single
      community. We cross-sectionally examined whether age, body mass index (BMI), and
      the interaction are significantly associated with hsCRP concentrations,
      independent of confounding factors. RESULTS: Multiple linear regression analyses
      for hsCRP showed that in men, age (beta = 0.169, P < 0.001) and BMI (beta =
      0.114, P = 0.004) as well as smoking status, triglycerides (TG), high-density
      lipoprotein cholesterol (HDL-C), uric acid, and gamma-glutamyl transferase (GGT)
      were significantly associated with hsCRP; and in women, age (beta = 0.203, P <
      0.001) and BMI (beta = 0.225, P < 0.001) as well as HDL-C, fasting plasma glucose
      (FPG), uric acid, GGT and high-molecular weight adiponectin were significantly
      associated with hsCRP. In addition to their direct associations, the interaction
      between age and BMI was also a significant and independent determinant for hsCRP
      in both men (F = 4.407, P = 0.036) and women (F = 5.487, P = 0.019). In
      participants aged < 75 years, overweight (BMI >= 25.0 kg/m(2)) persons were more
      likely to have a prevalence of elevated hsCRP concentrations (>= 1.00 mg/L)
      compared with the normal-weight (BMI <22.0 kg/m(2)), but such an association was
      not observed in those aged >= 75 years. CONCLUSIONS: Adiposity promotes low-grade
      systemic inflammation in community-dwelling persons aged <75 years.

PMID- 23880622
TI  - Elevated pregnancy-associated plasma protein A predicts myocardial dysfunction
      and death in severe sepsis.
AB  - BACKGROUND: Pregnancy-associated plasma protein A (PAPPA) is an emerging
      biomarker used in various medical fields but has yet to be evaluated in critical
      care medicine. This study evaluates the value of PAPPA as a biomarker in
      predicting myocardial dysfunction and 28-day mortality in patients with severe
      sepsis. METHODS: Serum concentrations of PAPPA and traditional cardiac biomarkers
      including cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) were
      measured on admission in 118 severely septic patients. The value of PAPPA for the
      diagnosis of sepsis-related myocardial dysfunction (SRMD) and for the prediction
      of 28-day mortality was subsequently evaluated using statistical methods.
      RESULTS: PAPPA was elevated (>=4.5 ng/mL) in 76 (64.4%) patients; patients with
      elevated PAPPA were more likely to have SRMD (76.3% vs. 38.1%, P < 0.001). By
      comparison of the area under the curve (AUC) in receiver operating
      characteristics analysis, PAPPA had comparable value (AUC 0.661, P = 0.003) to
      conventional biomarkers (BNP: AUC 0.699, P < 0.001; cTnI: AUC 0.647, P = 0.007)
      in the diagnosis of SRMD and offered superior value (AUC 0.771, P < 0.001) over
      them (all AUC<0.7, P > 0.05) in the prediction of 28-day death. Increased PAPPA
      (>=5.4 ng/mL) was associated with lower 28-day survival (chi(2) = 19.78, P <
      0.001) and independently predicted 28-day mortality in septic patients.
      CONCLUSIONS: Serum PAPPA concentration frequently increases in patients with
      severe sepsis and appears to be associated with SRMD. PAPPA can be used as a
      novel biomarker for the diagnosis of SRMD and the prediction of outcomes in
      critically ill patients.

PMID- 23880623
TI  - Single-nucleotide polymorphisms of IL-10 and IL-28B as predictors of the response
      of IFN therapy in HCV genotype 4-infected children.
AB  - BACKGROUND AND AIMS: Single-nucleotide polymorphisms (SNPs) in the IL-10 gene (
      1082 [rs1800896], -819 [rs3021097], and -592 [rs1800872]) and the IL-28B gene
      (rs12979860) in adults were shown to be associated with hepatitis C virus (HCV)
      clearance. The present study aimed to investigate the possible association of
      SNPs of IL-10 and IL-28B in predicting the treatment response of HCV genotype 4
      in pediatric patients. PATIENTS AND METHODS: A restriction fragment length
      polymorphism-polymerase chain reaction and real-time polymerase chain reaction
      techniques were used to genotype 34 pediatric patients with HCV genotype 4 for IL
      10 and IL-28B SNPs, respectively. Patients received pegylated interferon
      alpha/ribavirin for 48 weeks subdivided according to their response to treatment
      into responders and nonresponders; also, 20 healthy individuals served as
      controls. RESULTS: A significant difference (P < 0.005) was observed in SNP of IL
      28B rs12979860 frequencies between responders and nonresponders. In responders,
      CC genotype had greater frequency than CT and TT genotypes (60%, 30%, 10%),
      respectively, with C allele in its homozygous (CC) genotype more likely to
      respond to treatment than in its homozygous (TT) genotypes. SNPs of IL-10 at -819
      (rs3021097) showed significant differences in their genotype frequencies between
      responders and nonresponders to therapy, and TT genotype had greater frequency in
      responders than CT and CC (55%, 20%, 25%), respectively. Genotypes with T allele
      (CT/TT) showed higher rates of response than those with no T allele (CC).
      CONCLUSIONS: SNPs of the IL-28B gene at (rs12979860) CC genotype as well as the
      IL-10 gene SNPs at -819 (rs3021097)TT genotype can be used for predicting
      response to treatment before patients are prescribed the expensive pegylated
      interferon-alpha/ribavirin therapy.

PMID- 23880624
TI  - Liver disease after intensive care of premature baboons: histopathologic
      observations.
AB  - BACKGROUND AND OBJECTIVES: Cholestasis affects 50% of extremely low-birth-weight
      infants. Its etiology remains poorly understood and the extent of liver injury in
      these infants is unclear. The premature baboon model provides an opportunity to
      study neonatal liver disease. We characterize hepatic histopathologic changes in
      this model. METHODS: Archival tissue and data were obtained from the Southwest
      Foundation for Biomedical Research Primate Center, San Antonio, TX. Animals were
      selected based on history of antenatal steroid therapy and absence of sepsis or
      necrotizing enterocolitis with a protocol duration of at least 21 days and no
      early death (n = 45). Baboons had been treated per protocol in the neonatal
      intensive care unit (NICU). At necropsy, liver tissue was harvested and stored.
      Tissues from fetal gestational controls at similar ages were used for comparison
      (n = 28). Histologic changes were scored by consensus of 2 pathologists blinded
      to treatment group. Descriptive and comparative statistics were performed.
      RESULTS: Control fetal livers had extramedullary hematopoiesis (EMH) that
      decreased across the gestational range. There was evidence of hepatocyte iron
      storage and ongoing portal tract development. Livers of NICU-treated baboons had
      increased Kupffer cell hypertrophy and hemosiderosis. There was a shift away from
      erythroid EMH toward increased myeloid EMH. There was increased cholestasis,
      ductular proliferation, portal tract fibrosis, and steatosis in treated animals.
      CONCLUSIONS: We found pathologic changes in NICU-treated baboons comparable with
      findings reported in human infants. The baboon model of prematurity may be a
      useful tool to explore cholestasis and liver dysfunction in extremely low-birth
      weight infants.

PMID- 23880625
TI  - Effect of infant and follow-on formulas containing B lactis and galacto- and
      fructo-oligosaccharides on infection in healthy term infants.
AB  - OBJECTIVE: The aim of the present study was to compare the effect of
      Bifidobacterium animalis subspecies lactis (B lactis) alone or with 90% galacto
      oligosaccharide (GOS) and 10% fructo-oligosaccharide (FOS) on infections in
      infants. METHODS: In a multicenter trial, healthy, term, newborn infants ages 42
      days or younger whose mothers had decided not to breast-feed beyond this age
      received infant and follow-on formulas containing B lactis (10 colony-forming
      units/g) + GOS/FOS (0.4 g/100 mL, intention-to-treat, n = 261) or B lactis alone
      (107 colony-forming units/g, intention-to-treat, n = 267). Investigators accessed
      computer-generated randomization sequences via a remote server. Infants were
      exclusively fed formulas until 4 to 6 months of age and along with complementary
      feeding thereafter up to 12 months. The primary outcome was the mean number of
      annual infections reported by the investigators. Secondary outcomes were mean
      gains in anthropometric measurements, frequency of antibiotic use, and occurrence
      of adverse events based on investigators' records at each visit and
      gastrointestinal tolerance (daily stool frequency and consistency) and volume of
      formula intake recorded in 6-day diaries by parents. RESULTS: Mean +/- standard
      deviation infection rates in infants followed up to 12 months (full analysis set)
      were 4.9 +/- 3.2 per infant per year in the B lactis + GOS/FOS group (n = 219)
      and 4.5 +/- 3.0 per infant per year in the B lactis group (n = 220; analysis of
      variance, P = 0.18). Mean daily weight gain was slightly lower in the B lactis +
      GOS/FOS than the B lactis group (16.1 +/- 2.9 vs 16.6 +/- 2.6 g/day, P = 0.046),
      but was not clinically significant. Other outcomes were not significantly
      different between groups. CONCLUSIONS: Formulas containing B lactis + GOS/FOS did
      not reduce infection rates beyond those containing only B lactis.

PMID- 23880627
TI  - Psychosocial developmental trajectory of adolescents with inflammatory bowel
      disease.
AB  - BACKGROUND AND OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic,
      debilitating disorder occurring in young patients in the most productive period
      of their lives. Little is known about the effect on the developmental trajectory
      of adolescents growing up with IBD. The purpose of this study was to assess the
      psychosocial developmental trajectory ("course of life") and sociodemographic
      outcomes in adolescents with IBD compared with peers from the general population.
      METHODS: A total of 62 adolescents (response rate 74%, boys 51.6%, mean age 18.6
      years) completed the course of life questionnaire. RESULTS: Patients with IBD
      achieved fewer milestones on the domains of autonomy and social and psychosexual
      development compared with their healthy peers. They went less frequently on
      holidays without adults, had fewer jobs during secondary school, were less
      frequently going out to a bar/disco during secondary school, and were older when
      falling in love for the first time. After secondary school, patients with IBD
      were more often unemployed. CONCLUSIONS: Negative consequences in terms of
      psychosocial development are prevalent in adolescents with IBD. Physicians should
      be attentive to these consequences and provide additional support if necessary.
      During transition to adult clinic, these topics are of major importance and
      should be an integral component of the comprehensive care of chronically ill
      adolescents and young adults.

PMID- 23880626
TI  - Use of the noninvasive entero-test in the detection of Helicobacter pylori in
      children in an endemic area in Colombia.
AB  - BACKGROUND AND OBJECTIVE: Gastric infection with Helicobacter pylori (H pylori),
      a strong risk factor for gastric cancer, is highly prevalent in children residing
      in the Colombian Andes. We aimed to validate the use of the Entero-test to
      culture and genotype H pylori strains from asymptomatic Colombian children.
      METHODS: Children (ages 10-15 years, n = 110, 80 of which were H pylori positive
      by the urea breath test [UBT]) were subjected to the Entero-test, and strings
      were cultured and/or used for DNA extraction for polymerase chain reaction (PCR).
      These children had been treated for H pylori in 2007. A second population of
      children (ages 10-15 years, n = 95),which had not been previously treated, was
      also subjected to the Entero-test. RESULTS: Of UBT-positive children in the
      treated group, 29 of 80 (36%) Entero-test samples were H pylori culture positive;
      29 additional string extracts were tested by PCR for the H pylori virulence
      factors cagA and vacA. PCR from cultures and extracts yielded a sensitivity of
      74% and specificity of 87%. In the untreated group, 16 of 94 UBT-positive
      children (17%) produced Entero-tests that were culture positive. Fifty-eight of
      94 (62%) string extracts were PCR positive for cagA and/or vacA. In previously
      treated children, H pylori strains were more often the less virulent vacA s2 (P =
      0.001), m2 (P = 0.006), and i2 genotypes (P = 0.039). CONCLUSIONS: The Entero
      test may be used as a noninvasive test to detect H pylori in asymptomatic
      children residing in high-risk areas for gastric cancer. Treatment of H pylori in
      children was associated with less virulent genotypes.

PMID- 23880628
TI  - Young children with Behcet disease have more intestinal involvement.
AB  - OBJECTIVE: Gastrointestinal (GI) involvement in childhood Behcet disease (BD) is
      not well understood. We aimed to clarify the intestinal presentation in children
      with BD. METHODS: Medical records of 85 children with recurrent oral ulcers
      between 1990 and 2010 at the National Taiwan University Hospital were reviewed
      retrospectively. Twenty of them who fulfilled the Mason and Barnes criteria for
      the diagnosis of childhood BD were enrolled. The clinical and laboratory
      characteristics were analyzed. RESULTS: Among 20 patients, the median age at
      diagnosis was 13.2 years. The common presentations included oral ulcers (100%),
      genital ulcers (70%), skin lesions (65%), and GI symptoms (50%). Five of 10
      patients with GI symptoms received endoscopic examinations and all had ulcers.
      Divided by the age of 10, patients younger than 10 years tended to have higher
      rates of GI symptoms initially and intestinal ulcers (P = 0.002 and 0.015,
      respectively). Platelet count was significantly lower in young patients (P =
      0.0151). Patients without GI symptoms had higher rates of skin involvement than
      patients with GI symptoms (P = 0.019). CONCLUSIONS: Young children with BD tended
      to have more GI presentations. For children with BD younger than 10 years having
      GI symptoms, endoscopic examinations may be considered.

PMID- 23880629
TI  - Extraintestinal Hodgkin disease in a young man with Crohn disease treated with
      multiple immunosuppresive therapies.

PMID- 23880630
TI  - World Health Organization 2006 child growth standards and 2007 growth reference
      charts: A discussion paper by the committee on Nutrition of the European Society
      for Pediatric Gastroenterology, Hepatology, and Nutrition.
AB  - Growth charts are essential for evaluating children's health including their
      nutrition; however, the evaluation of child growth trajectories and consequently
      the decision to intervene are highly dependent on the growth charts used. The aim
      of this discussion paper of the European Society for Paediatric Gastroenterology,
      Hepatology, and Nutrition Committee on Nutrition is to provide information on the
      background and rationale of the World Health Organization (WHO) 2006 child growth
      standards and WHO 2007 growth reference charts, describe their development,
      outline their main innovative aspects, discuss potential limitations, and make
      recommendations. WHO 2006 child growth standards (0-5 years) are based on
      prospectively collected data describing the growth of healthy infants who were
      breast-fed according to WHO recommendations, showing a pattern of linear growth,
      which is remarkably consistent between different countries and ethnic groups. WHO
      2007 growth reference charts (5-19 years) are based mainly on a re-analysis of
      National Centre for Health Statistics data from 1977, without information on
      feeding. European Society for Paediatric Gastroenterology, Hepatology, and
      Nutrition Committee on Nutrition recommends that WHO child growth standards
      should be used to monitor growth in all children in the age range 0 to 2 years in
      Europe, whether breast- or formula-fed, and that they should be considered to be
      used in the age range 2 to 5 years. Implementation of the WHO child growth
      standards should be preceded by evaluation of the implication of their use on
      national healthcare policies. Health professionals should be guided on their use
      and interpretation and an adequate communication strategy should be available
      locally to ensure that parents receive clear and consistent advice. The decision
      on whether to implement the WHO growth references (5-19 years) should be made by
      national bodies because the growth pattern during the 5- to 19-year period
      differs between populations. 

PMID- 23880631
TI  - Congenitally corrected transposition of the great vessels associated with
      morphological right ventricular non-compaction presenting with supraventricular
      tachycardia.

PMID- 23880632
TI  - Perfect crystals grown from imperfect interfaces.
AB  - The fabrication of advanced devices increasingly requires materials with
      different properties to be combined in the form of monolithic heterostructures.
      In practice this means growing epitaxial semiconductor layers on substrates often
      greatly differing in lattice parameters and thermal expansion coefficients. With
      increasing layer thickness the relaxation of misfit and thermal strains may cause
      dislocations, substrate bowing and even layer cracking. Minimizing these
      drawbacks is therefore essential for heterostructures based on thick layers to be
      of any use for device fabrication. Here we prove by scanning X-ray
      nanodiffraction that mismatched Ge crystals epitaxially grown on deeply patterned
      Si substrates evolve into perfect structures away from the heavily dislocated
      interface. We show that relaxing thermal and misfit strains result just in
      lattice bending and tiny crystal tilts. We may thus expect a new concept in which
      continuous layers are replaced by quasi-continuous crystal arrays to lead to
      dramatically improved physical properties. 

PMID- 23880633
TI  - Cloning and characterization of miRNAs and their targets, including a novel miRNA
      targeted NBS-LRR protein class gene in apple (Golden Delicious).
AB  - MicroRNA (miRNA) has emerged as an important regulator of gene expression in
      plants. 146 miRNAs were identified from apple (Malus domestica cv. Golden
      Delicious) by bioinformatic analysis and RNA library sequencing. From these, 135
      were conserved and 11 were novel miRNAs. Target analysis predicted one of the
      novel miRNAs, Md-miRLn11 (Malus domestica microRNA Ln11), targeted an apple
      nucleotide-binding site (NBS)-leucine-rich repeat (LRR) class protein coding gene
      (Md-NBS). 5' RACE assay confirmed the ability of Md-miRLn11 to cleave Md-NBS at
      the 11-12-nt position. Analysis of the expression of Md-miRLn11 and Md-NBS during
      the optimum invasion period in 40 apple varieties showed that the expression of
      Md-NBS gene in resistant varieties is higher than in susceptible varieties, with
      an inverse pattern for Md-miRLn11. Seedlings from the resistant apple variety
      'JiGuan' were used to carry out an Agrobacterium infiltration assay, and then
      inoculated with the apple leaf spot disease. The result showed a clear decline of
      disease resistance in JiGuan apples. In contrast, the susceptible variety 'FuJi'
      infiltrated with the Md-NBS gene showed a significant increase in disease
      resistance. Based on the above results, we propose that Md-miRLn11 regulates Md
      NBS gene expression in particular under the condition of pathogen infection, and
      that the Md-miRLn11 targeting P-loop site may regulate many NBS-LRR protein class
      genes in woody plants. 

PMID- 23880634
TI  - Not all droughts are created equal: translating meteorological drought into woody
      plant mortality.
AB  - Widespread drought-induced mortality of woody plants has recently occurred
      worldwide, is likely to be exacerbated by future climate change and holds large
      ecological consequences. Yet despite decades of research on plant-water
      relations, the pathways through which drought causes plant mortality are poorly
      understood. Recent work on the physiology of tree mortality has begun to reveal
      how physiological dysfunction induced by water stress leads to plant death;
      however, we are still far from being able to predict tree mortality using easily
      observed or modeled meteorological variables. In this review, we contend that, in
      order to fully understand when and where plants will exceed mortality thresholds
      when drought occurs, we must understand the entire path by which precipitation
      deficit is translated into physiological dysfunction and lasting physiological
      damage. In temperate ecosystems with seasonal climate patterns, precipitation
      characteristics such as seasonality, timing, form (snow versus rain) and
      intensity interact with edaphic characteristics to determine when and how much
      water is actually available to plants as soil moisture. Plant and community
      characteristics then mediate how quickly water is used and seasonally varying
      plant physiology determines whether the resulting soil moisture deficit is
      physiologically damaging. Recent research suggests that drought seasonality and
      timing matter for how an ecosystem experiences drought. But, mortality studies
      that bridge the gaps between climatology, hydrology, plant ecology and plant
      physiology are rare. Drawing upon a broad hydrological and ecological
      perspective, we highlight key and underappreciated processes that may mediate
      drought-induced tree mortality and propose steps to better include these
      components in current research.

PMID- 23880635
TI  - Optimizing field patching in passively scattered proton therapy with the use of
      beam current modulation.
AB  - Treatment plans for patched-field proton therapy may not be clinically acceptable
      due to the dose heterogeneity introduced in the target when combining the dose
      distributions from two separate fields. MCNPX simulations were performed for
      various configurations of the Mevion S250 beamline to determine spread-out Bragg
      peak dose distributions and patched-field treatment plans delivered using a
      rotating modulator wheel to depths in the clinically relevant range between 5.0
      and 30.0 cm. The dose non-uniformity (DNU) metric was defined as the difference
      between the maximum and minimum dose relative to the prescription observed in a
      patched dose distribution. The DNU was first evaluated for dose distributions
      from a standard delivery using constant beam current and combining through-field
      lateral dose profiles and with patch-field distal dose profiles. Patch-field
      distal dose profiles were then optimized using beam current modulation in an
      attempt to better complement the through-field lateral dose profiles when
      combined into a patched dose distribution. Using standard deliveries, DNU was 10%
      or less only when patching lateral profiles 12.5-17.5 cm deep. Significantly
      greater DNU was observed for patches outside of this range, at times exceeding
      35%. Using optimized distal profiles, DNU was reduced to 10% or less for all
      lateral profiles deeper than 15.0 cm. Optimizing beam current modulation was
      found to create distal profiles with more gradual dose falloff than found in a
      standard delivery, allowing optimized distal dose distributions to sum more
      homogeneously with lateral dose distributions. The hot or cold spots that often
      appear in patched dose distributions from standard deliveries may therefore be
      mitigated by optimizing beam current. This method may also be applied to systems
      other than the Mevion system to further improve patched-field dose homogeneity.

PMID- 23880636
TI  - Diffusion-weighted magnetic resonance imaging for predicting and detecting the
      early response to chemoradiotherapy of advanced esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: The aim of this study was to investigate the utility of the apparent
      diffusion coefficient (ADC) value in diffusion-weighted magnetic resonance
      imaging (DWMRI) for prediction and early detection of treatment response in
      advanced esophageal squamous cell carcinoma. METHOD: DWMRI was performed in 27
      patients with primary cT4 esophageal carcinoma that were undergoing
      chemoradiotherapy before treatment and after 20 and 40 Gy. We calculated tumor
      ADCs and association of the treatment effect between responders and
      nonresponders. RESULTS: The ADC at the time of 20 Gy was significantly higher in
      responders compared to nonresponders (1.13 vs. 0.93; p = 0.005). The ADC cut-off
      value was set at 1.00 * 10(-3) mm(2)/s and the ADC predicted the responders with
      a sensitivity, positive predictive value and accuracy of 79, 73 and 74%,
      respectively. The increased rate of the ADC at the time of 20 Gy (DeltaADC20) was
      also significantly higher in responders compared to nonresponders (35.4 vs. 1.5%;
      p = 0.0007). An ADC cut-off value for DeltaADC20 of 15% predicted the responders
      with a sensitivity, positive predictive value and accuracy of 71, 100 and 85%,
      respectively. CONCLUSION: The ADC values predicted the prognosis of patients with
      advanced esophageal squamous cell carcinoma as well as the treatment response.

PMID- 23880638
TI  - Designing ternary cocrystals with hydrogen bonds and halogen bonds.
AB  - A graded selection of hydrogen bonds and halogen bonds allows for the isolation
      of 2 : 1 : 1 ternary cocrystals of the general form 4-nitrobenzamide : diacid :
      1,4-dihalogenated benzene, which are mediated by the amide-acid and I...O2N
      supramolecular synthons.

PMID- 23880637
TI  - Half pint/Puf68 is required for negative regulation of splicing by the SR
      splicing factor Transformer2.
AB  - The SR family of proteins plays important regulatory roles in the control of
      alternative splicing in a wide range of organisms. These factors affect splicing
      through both positive and negative controls of splice site recognition by pre
      spliceosomal factors. Recent studies indicate that the Drosophila SR factor
      Transformer 2 (Tra2) activates and represses splicing through distinct and
      separable effector regions of the protein. While the interactions of its Arg-Ser
      rich activator region have been well studied, cofactors involved in splicing
      repression have yet to be found. Here we use a luciferase-based splicing reporter
      assay to screen for novel proteins necessary for Tra2-dependent repression of
      splicing. This approach identified Half pint, also known as Puf68, as a co
      repressor required for Tra2-mediated autoregulation of the M1 intron. In vivo,
      Half pint is required for Tra2-dependent repression of M1 splicing but is not
      necessary for Tra2-dependent activation of doublesex splicing. Further
      experiments indicate that the effect of Hfp is sequence-specific and that it
      associates with these target transcripts in cells. Importantly, known M1 splicing
      regulatory elements are sufficient to sensitize a heterologous intron to Hfp
      regulation. Two alternative proteins deriving from Hfp transcripts, Hfp68, and
      Hfp58, were found to be expressed in vivo but differed dramatically in their
      effect on M1 splicing. Comparison of the cellular localization of these forms in
      S2 cells revealed that Hfp68 is predominantly localized to the nucleus while
      Hfp58 is distributed across both the nucleus and cytoplasm. This accords with
      their observed effects on splicing and suggests that differential
      compartmentalization may contribute to the specificity of these isoforms.
      Together, these studies reveal a function for Half pint in splicing repression
      and demonstrate it to be specifically required for Tra2-dependent intron
      inclusion. 

PMID- 23880639
TI  - Fabrication of bioactive conduits containing the fibroblast growth factor 1 and
      neural stem cells for peripheral nerve regeneration across a 15 mm critical gap.
AB  - Nerve conduits are often used in combination with bioactive molecules and stem
      cells to enhance peripheral nerve regeneration. In this study, the acidic
      fibroblast growth factor 1 (FGF1) was immobilized onto the
      microporous/micropatterned poly (D, L-lactic acid) (PLA) nerve conduits after
      open air plasma treatment. PLA substrates grafted with chitosan in the presence
      of a small amount of gold nanoparticles (nano Au) showed a protective effect on
      the activity of the immobilized FGF1 in vitro. Different conduits were tested for
      their ability to bridge a 15 mm critical gap defect in a rat sciatic nerve injury
      model. Axon regeneration and functional recovery were evaluated by histology,
      walking track analysis and electrophysiology. Among different conduits, PLA
      conduits grafted with chitosan-nano Au and the FGF1 after plasma activation had
      the greatest regeneration capacity and functional recovery in the experimental
      animals. When the above conduit was seeded with aligned neural stem cells, the
      efficacy was further enhanced and it approached that of the autograft group. This
      work suggested that microporous/micropatterned nerve conduits containing
      bioactive growth factors may be successfully fabricated by micropatterning
      techniques, open plasma activation, and immobilization, which, combined with
      aligned stem cells, may synergistically contribute to the regeneration of the
      severely damaged peripheral nerve.

PMID- 23880640
TI  - Chromatin computation: epigenetic inheritance as a pattern reconstruction
      problem.
AB  - Eukaryotic histones carry a diverse set of specific chemical modifications that
      accumulate over the life-time of a cell and have a crucial impact on the cell
      state in general and the transcriptional program in particular. Replication
      constitutes a dramatic disruption of the chromatin states that effectively
      amounts to partial erasure of stored information. To preserve its epigenetic
      state the cell reconstructs (at least part of) the histone modifications by means
      of processes that are still very poorly understood. A plausible hypothesis is
      that the different combinations of reader and writer domains in histone-modifying
      enzymes implement local rewriting rules that are capable of "recomputing" the
      desired parental modification patterns on the basis of the partial information
      contained in that half of the nucleosomes that predate replication. To test
      whether such a mechanism is theoretically feasible, we have developed a flexible
      stochastic simulation system (available at http://www.bioinf.uni
      leipzig.de/Software/StoChDyn) for studying the dynamics of histone modification
      states. The implementation is based on Gillespie's approach, i.e., it models the
      master equation of a detailed chemical model. It is efficient enough to use an
      evolutionary algorithm to find patterns across multiple cell divisions with high
      accuracy. We found that it is easy to evolve a system of enzymes that can
      maintain a particular chromatin state roughly stable, even without explicit
      boundary elements separating differentially modified chromatin domains. However,
      the success of this task depends on several previously unanticipated factors,
      such as the length of the initial state, the specific pattern that should be
      maintained, the time between replications, and chemical parameters such as
      enzymatic binding and dissociation rates. All these factors also influence the
      accumulation of errors in the wake of cell divisions. 

PMID- 23880641
TI  - Ostomy care and management: a systematic review.
AB  - The frequency of ostomy surgery in Canada is not known, but it is estimated that
      approximately 13,000 ostomy surgeries are performed annually in Canada. This
      systematic review incorporates evidence for the assessment and management of
      colostomies, ileostomies, and urostomies, as well as the peristomal skin. The
      review was completed as part of a best practice guideline document generated by a
      task force appointed by the Registered Nurses' Association of Ontario. 

PMID- 23880642
TI  - Lysosome/lipid droplet interplay in metabolic diseases.
AB  - Lysosomes and lipid droplets are generally considered as intracellular
      compartments with divergent roles in cell metabolism, lipid droplets serving as
      lipid reservoirs in anabolic pathways, whereas lysosomes are specialized in the
      catabolism of intracellular components. During the last few years, new insights
      in the biology of lysosomes has challenged this view by providing evidence for
      the importance of lysosome recycling as a sparing mechanism to maintain cellular
      fitness. On the other hand the understanding of lipid droplets has evolved from
      an inert intracellular deposit toward the status of an intracellular organelle
      with dynamic roles in cellular homeostasis beyond storage. These unrelated
      aspects have also recently converged in the finding of unexpected lipid
      droplet/lysosome communication through autophagy, and the discovery of lysosome
      mediated lipid droplet degradation called lipopagy. Furthermore, adipocytes which
      are professional cells for lipid droplet formation were also shown to be active
      in peptide antigen presentation a pathway requiring lysosomal activity. The
      potential importance of lipid droplet/lysosome interplay is discussed in the
      context of metabolic diseases and the setting of chronic inflammation. 

PMID- 23880643
TI  - Impact of low oxygen on the secretome of human adipose-derived stromal/stem cell
      primary cultures.
AB  - Tissue fibrosis can lead to organ dysfunction, patient morbidity, and mortality.
      Adipose-derived Stromal/stem Cells (ASCs) represent a potential therapeutic.
      Immediately following grafting, ASCs would reside in a lower O2 environment. ASC
      secretome was examined under 5% O2 ("low O2") and 21% O2 ("ambient O2") culture
      conditions. ASCs from five female donors were cultured in low or ambient O2
      conditions for 3 days and pooled conditioned medium was compared by two
      dimensional liquid chromatography and tandem mass spectrometry (2D-LC-MS/MS). Of
      71 proteins identified, five proteins involved in extracellular matrix (ECM)
      remodeling exhibited >=2-fold decrease under low O2 culture and were confirmed by
      Western immunoblot and qRT-PCR: fibronectin 1, TGF-beta1-induced protein (betaig
      h3), osteonectin, and collagens type 1alpha1 and alpha2. ELISAs performed using
      10 donors also confirmed significant decreases during low O2 culture in 4-6 ASC
      donors. For low abundant proteins, a 36 cytokine/chemokine array was performed.
      Fifteen cytokines/chemokines including Type 2 cytokines IL-13, MCP-1, and CD40
      ligand were detected in ambient O2 ASC medium. IL-6 was detected in low O2 but
      not ambient O2 ASC medium. These findings demonstrate that low O2 ASC exposure
      resulted in reduced ECM protein and Type 2 cytokine secretions that are
      significant with regard to inflammation in fibrosis. 

PMID- 23880644
TI  - Proteomic techniques for characterisation of mesenchymal stem cell secretome.
AB  - Mesenchymal stem cells (MSCs) are multipotent cells with a substantial potential
      in human regenerative medicine due to their ability to migrate to sites of
      injury, capability to suppress immune response and accessibility in large amount
      from patient's own bone marrow or fat tissue. It has been increasingly observed
      that the transplanted MSCs did not necessarily engraft and differentiate at the
      site of injury but might exert their therapeutic effects through secreted trophic
      signals. The MSCs secrete a variety of autocrine/paracrine factors, called
      secretome, that support regenerative processes in the damaged tissue, induce
      angiogenesis, protect cells from apoptotic cell death and modulate immune system.
      The cell culture medium conditioned by MSCs or osteogenic, chondrogenic as well
      as adipogenic precursors derived from MSCs has become a subject of intensive
      proteomic profiling in the search for and identification of released factors and
      microvesicles that might be applicable in regenerative medicine. Jointly with the
      methods for MSC isolation, expansion and differentiation, proteomic analysis of
      MSC secretome was enabled recently mainly due to the extensive development in
      protein separation techniques, mass spectrometry, immunological methods and
      bioinformatics. This review describes proteomic techniques currently applied or
      prospectively applicable in MSC secretomics, with a particular focus on
      preparation of the secretome sample, protein/peptide separation, mass
      spectrometry and protein quantification techniques, analysis of posttranslational
      modifications, immunological techniques, isolation and characterisation of
      secreted vesicles and exosomes, analysis of cytokine-encoding mRNAs and
      bioinformatics. 

PMID- 23880645
TI  - Sprouty genes regulate proliferation and survival of human embryonic stem cells.
AB  - Sprouty (Spry) genes encode negative regulators of receptor tyrosine kinase (RTK)
      signaling, which plays important roles in human embryonic stem cells (hESCs).
      SPRY2 and SPRY4 are the two most highly expressed Sprouty family members in
      hESCs, suggesting that they may influence self-renewal. To test this hypothesis,
      we performed siRNA-mediated knock down (KD) studies. SPRY2 KD resulted in
      increased cell death and decreased proliferation, whereas SPRY4 KD enhanced
      survival. In both cases, after KD the cells were able to differentiate into cells
      of the three germ layers, although after SPRY2 KD there was a tendency toward
      increased ectodermal differentiation. SPRY2 KD cells displayed impaired
      mitochondrial fusion and cell membrane damage, explaining in part the increased
      cell death. These data indicate that Sprouty genes regulate pathways involved in
      proliferation and cell death in hESCs. 

PMID- 23880647
TI  - The state of the art in diagnosis and management of vestibulopathy.

PMID- 23880646
TI  - Rotavirus G9P[4] in 3 countries in Latin America, 2009-2010.

PMID- 23880648
TI  - Imaging for evaluation of cholesteatoma: current concepts and future directions.
AB  - PURPOSE OF REVIEW: To examine the rationale and utility of imaging in patients
      with known or suspected cholesteatoma, with emphasis on high-resolution computed
      tomography (HRCT) and diffusion-weighted MRI (DW-MRI). RECENT FINDINGS: The
      initial diagnosis of cholesteatoma is largely based on patient history and
      clinical findings. HRCT scan can be a useful adjunct to define the presence of
      pathologic soft tissue in the temporal bone, and the extent of bony erosion, and
      inform the otologic surgeon about expected findings at the time of surgery.
      Although MRI has not traditionally been used in the evaluation of cholesteatoma
      given its poor resolution of bone anatomy, recent advances in DW-MRI sequences
      allow for high sensitivity and specificity in identifying the presence of
      cholesteatoma. More specifically, non-echo-planar DW-MRI is superior in the
      detection of residual or recurrent cholesteatoma compared to delayed-contrast MRI
      and echo-planar DW-MRI. SUMMARY: HRCT and DW-MRI offer complementary anatomic
      information that can be used effectively in the management of cholesteatoma. DW
      MRI imaging has proven to be a reliable method for detecting residual or
      recurrent cholesteatomas down to 3 mm in size, and allows radiologic
      differentiation between cholesteatoma and other soft tissue. As more centers
      implement DW-MRI imaging for detecting residual or recurrent cholesteatoma, there
      will likely be less need for second-look surgery, thereby potentially decreasing
      associated morbidity and surgical costs.

PMID- 23880649
TI  - Effect of 200 mEq/L Na+ hypertonic saline resuscitation on systemic inflammatory
      response and oxidative stress in severely burned rats.
AB  - BACKGROUND: Excessive release of inflammatory mediators and oxidative stress play
      important roles in the increased vascular permeability and systemic edema during
      the early stage of severe burn. This study investigates the effect of 200 mEq/L
      Na(+) hypertonic saline (HS) on systemic inflammatory response and oxidative
      stress in severely burned rats. MATERIALS AND METHODS: Sprague-Dawley rats were
      divided into three groups: sham group, burn plus lactated Ringer's group, and
      burn plus HS group. Lung edema was assessed in terms of wet-weight-to-dry-weight
      ratio. Tumor necrosis factor alpha and interleukin 6 concentrations in serum were
      examined by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells
      were isolated and the expression of p38 mitogen-activated protein kinase was
      determined by Western blot analysis. The lung and intestinal concentrations of
      malondialdehyde, an indicator of oxidative stress, were also measured. RESULTS:
      Resuscitation with 200 mEq/L Na(+) HS significantly decreased the lung wet-weight
      to-dry-weight ratio and abolished hyponatremia induced by burn injury. HS
      treatment also prevented the increases of myeloperoxidase activity and
      malondialdehyde content in the lung and intestine of severely burned rats.
      However, there were no significant differences, either in serum tumor necrosis
      factor alpha and interleukin 6 concentrations or with respect to the p38 mitogen
      activated protein kinase expression in peripheral blood mononuclear cells,
      between the burn plus lactated Ringer's group and burn plus HS group (P > 0.05).
      CONCLUSIONS: Initial resuscitation with 200 mEq/L Na(+) HS after severe burn
      injury decreases pulmonary edema, prevents hyponatremia, and attenuates oxidative
      stress, but is not capable of inhibiting the systemic inflammatory response.

PMID- 23880650
TI  - TC-1 (c8orf4) enhances aggressive biologic behavior in lung cancer through the
      Wnt/beta-catenin pathway.
AB  - BACKGROUND: The thyroid cancer-1 (TC-1) or c8orf4 gene encodes a 106-residue
      naturally disordered protein that has been found to be associated with thyroid,
      gastric, and breast cancer. A recent study has indicated that the protein
      functions as a positive regulator in the Wnt/beta-catenin signaling pathway in
      human breast cancer. However, no research has been done in the area of lung
      cancer. Therefore, the goal of the present study was to confirm the relationship
      among TC-1, lung cancer, and the Wnt/beta-catenin signaling pathway. MATERIALS
      AND METHODS: The expression of TC-1 was immunohistochemically examined in 147
      patients with non-small-cell lung cancer. TC-1-overexpressed and silenced A549
      cells were infected using lentivirus and MTT cell proliferation analysis, and
      Matrigel invasion assays and scratch-wound assays were performed to confirm the
      biologic behavioral changes in different A549 cell subsets. The Wnt/beta-catenin
      signaling pathway, key gene beta-catenin, target genes of vascular endothelial
      growth factor, cyclin D1, matrix metalloproteinase-7, c-myc, and survivin were
      tested at the mRNA and protein level. RESULTS: TC-1 was detected in 97 of the 147
      non-small-cell lung cancer primary tumor specimens, and its expression correlated
      with the TNM stage and regional lymph node metastasis (P < 0.01). In vitro
      experiments demonstrated that TC-1 expression affected both proliferation and
      invasion in the A549 cell line. Furthermore, expression of TC-1 protein affected
      the Wnt/beta-catenin signaling pathway's downstream genes, such as vascular
      endothelial growth factor and matrix metalloproteinase-7, at the mRNA and protein
      level. CONCLUSIONS: TC-1 expression is associated with aggressive biologic
      behavior in lung cancer and might coordinate with the Wnt/beta-catenin pathway as
      a positive upstream regulator that induces these behaviors.

PMID- 23880651
TI  - Treatment of osteonecrosis in the knee joint of a rabbit using autologous
      cultured osteoblasts.
AB  - BACKGROUND: [corrected] To develop a successful treatment modality for
      osteonecrosis, an appropriate animal model is essential. We have proposed a new
      osteonecrosis model that shows the total amount of necrosis and in which we
      observed new bone formation after transplanting autologous cultured osteoblasts.
      MATERIALS AND METHODS: The femoral condyles of the right knees of New Zealand
      white rabbits were exposed after dissecting the ligaments surrounding the distal
      femur. After which, the metaphyseal-diaphyseal junction was cut using a saw, and
      the entire femoral condyle was isolated. After three liquid nitrogen treatments,
      the isolated femoral condyle was internally fixated to the femoral shaft using
      two or three Kirschner wires. Bone marrow isolated from the iliac crest was
      cultivated to differentiate it into osteoblasts, and the cultured cells were then
      injected into the necrotic bone. RESULTS: Viable osteocytes with well-stained
      nuclei were not present in the necrotic areas at any stage of the development of
      the osteonecrosis model within 24 wk after osteonecrosis induction. However, new
      bone formation with osteocytes and blood vessels was observed in the necrotic
      bone 12 wk after transplanting the autologous cultured osteoblasts. CONCLUSIONS:
      The distal femoral condyle of the rabbit is an appropriate model for
      demonstrating osteonecrosis and treatment evaluation owing to its easy
      reproducibility and treatment interpretation. Therefore, autologous cultured
      osteoblast treatment would seem to be a potentially successful treatment modality
      for osteonecrosis.

PMID- 23880653
TI  - Highlights in metastatic colorectal cancer from the 2013 American Society of
      Clinical Oncology Gastrointestinal Cancers Symposium.

PMID- 23880655
TI  - Acute ingestion of sugar-free red bull energy drink has no effect on upper body
      strength and muscular endurance in resistance trained men.
AB  - Consumption of energy drinks by both recreational and competitive athletes has
      increased dramatically in recent years. The primary ingredients in many energy
      drinks include caffeine (CAF) in various forms and taurine. The purpose of this
      randomized, double-blind, crossover study was to examine the effect of sugar-free
      (SF) Red Bull (RB) containing CAF and taurine to a CAF only drink and a SF CAF
      free placebo (PL) on 1 repetition maximum (1RM) bench press (BP) and the volume
      load (VL; repetitions * kg at 70% 1RM) during one BP set to failure in
      experienced lifters. Seventeen college-age men randomly received the following:
      (A) 500 mL of SF-RB containing CAF (160 mg) and taurine (2000 mg); (B) 500 mL of
      a SF drink containing CAF only (160 mg); or (C) a SF CAF-free 500 mL PL drink 60
      minutes before testing on 3 separate occasions. After a standard warm-up, the 1RM
      was determined for each subject and, after 5 minutes rest, they completed
      repetitions to failure at 70% of their 1RM to assess VL. Differences between
      trials for 1RM BP and the VL were identified using repeated measures analysis of
      variance (p < 0.05). The results indicated that neither SF-RB nor the CAF drink
      had any effect on 1RM BP (115.13 +/- 16.19 kg and 114.87 +/- 16.16 kg,
      respectively) or VL (1173.08 +/- 170.66 kg and 1164.14 +/- 147.03 kg,
      respectively) compared with PL (1RM = 114.07 +/- 16.09 kg; VL = 1141.46 +/-
      193.41 kg). Although the CAF content in the energy drinks used in the present
      study was low (~2.0 mg/kg), the finding of no effect of the CAF containing energy
      drinks for 1RM BP are in agreement with previous studies using intakes up to 6.0
      mg/kg. These findings suggest that SF-RB has no effect on upper body 1RM strength
      or VL in resistance trained men.

PMID- 23880656
TI  - Handgrip strength in autism spectrum disorder compared with controls.
AB  - The study examined handgrip strength in participants diagnosed with an autism
      spectrum disorder (ASD) as compared with neurotypical children. Thirty-three
      children, aged 2-17 years, with an ASD and 33 gender-, race-, and age-matched
      neurotypical controls were tested using a handgrip dynamometer. The handgrip
      strength in participants with an ASD was significantly (p < 0.0001) lower than
      the neurotypical controls. The mean handgrip strength was 39.4 +/- 17.7 kPa in
      children with ASD and 65.1 +/- 26.7 kPa in controls. The results support the
      hypothesis that children with an ASD have significantly poorer handgrip strength
      as compared with neurotypical children. Because the handheld dynamometer has been
      shown to be a valid tool for measuring overall muscle strength, the results
      suggest that children with ASD have muscle weakness. Future studies are needed to
      determine the extent of muscle weakness in ASD, its ramifications, and the
      possible benefits of muscle strengthening. The present study provides support for
      the use of handgrip strength as a tool for the assessment of targeted treatment
      in ASD.

PMID- 23880652
TI  - hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective
      effects against ischaemic brain injury.
AB  - Human pluripotent stem cells (hPSCs) have been differentiated to astroglia, but
      the utilization of hPSC-derived astroglia as cell therapy for neurological
      diseases has not been well studied. Astroglia are heterogeneous, and not all
      astroglia are equivalent in promoting neural repair. A prerequisite for cell
      therapy is to derive defined cell populations with superior therapeutic effects.
      Here we use an Olig2-GFP human embryonic stem cell (hESC) reporter to demonstrate
      that hESC-derived Olig2(+) progenitors generate a subtype of previously
      uncharacterized astroglia (Olig2PC-Astros). These Olig2PC-Astros differ
      substantially from astroglia differentiated from Olig2-negative hESC-derived
      neural progenitor cells (NPC-Astros), particularly in their neuroprotective
      properties. When grafted into brains subjected to global ischaemia, Olig2PC
      Astros exhibit superior neuroprotective effects and improved behavioural outcome
      compared to NPC-Astros. Thus, this new paradigm of human astroglial
      differentiation is useful for studying the heterogeneity of human astroglia, and
      the unique Olig2PC-Astros may constitute a new cell therapy for treating cerebral
      ischaemia and other neurological diseases. 

PMID- 23880657
TI  - The importance of a priori sample size estimation in strength and conditioning
      research.
AB  - The statistical power, or sensitivity of an experiment, is defined as the
      probability of rejecting a false null hypothesis. Only 3 factors can affect
      statistical power: (a) the significance level (alpha), (b) the magnitude or size
      of the treatment effect (effect size), and (c) the sample size (n). Of these 3
      factors, only the sample size can be manipulated by the investigator because the
      significance level is usually selected before the study, and the effect size is
      determined by the effectiveness of the treatment. Thus, selection of an
      appropriate sample size is one of the most important components of research
      design but is often misunderstood by beginning researchers. The purpose of this
      tutorial is to describe procedures for estimating sample size for a variety of
      different experimental designs that are common in strength and conditioning
      research. Emphasis is placed on selecting an appropriate effect size because this
      step fully determines sample size when power and the significance level are
      fixed. There are many different software packages that can be used for sample
      size estimation. However, I chose to describe the procedures for the G*Power
      software package (version 3.1.4) because this software is freely downloadable and
      capable of estimating sample size for many of the different statistical tests
      used in strength and conditioning research. Furthermore, G*Power provides a
      number of different auxiliary features that can be useful for researchers when
      designing studies. It is my hope that the procedures described in this article
      will be beneficial for researchers in the field of strength and conditioning.

PMID- 23880658
TI  - The development of a 3D immunocompetent model of human skin.
AB  - As the first line of defence, skin is regularly exposed to a variety of
      biological, physical and chemical insults. Therefore, determining the skin
      sensitization potential of new chemicals is of paramount importance from the
      safety assessment and regulatory point of view. Given the questionable biological
      relevance of animal models to human as well as ethical and regulatory pressure to
      limit or stop the use of animal models for safety testing, there is a need for
      developing simple yet physiologically relevant models of human skin. Herein, we
      describe the construction of a novel immunocompetent 3D human skin model
      comprising of dendritic cells co-cultured with keratinocytes and fibroblasts.
      This model culture system is simple to assemble with readily-available components
      and importantly, can be separated into its constitutive individual layers to
      allow further insight into cell-cell interactions and detailed studies of the
      mechanisms of skin sensitization. In this study, using non-degradable microfibre
      scaffolds and a cell-laden gel, we have engineered a multilayer 3D
      immunocompetent model comprised of keratinocytes and fibroblasts that are
      interspersed with dendritic cells. We have characterized this model using a
      combination of confocal microscopy, immuno-histochemistry and scanning electron
      microscopy and have shown differentiation of the epidermal layer and formation of
      an epidermal barrier. Crucially the immune cells in the model are able to migrate
      and remain responsive to stimulation with skin sensitizers even at low
      concentrations. We therefore suggest this new biologically relevant skin model
      will prove valuable in investigating the mechanisms of allergic contact
      dermatitis and other skin pathologies in human. Once fully optimized, this model
      can also be used as a platform for testing the allergenic potential of new
      chemicals and drug leads.

PMID- 23880660
TI  - Carboxy terminal modifications of the P0 protein reveal alternative mechanisms of
      nuclear ribosomal stalk assembly.
AB  - The P0 scaffold protein of the ribosomal stalk is mainly incorporated into pre
      ribosomes in the cytoplasm where it replaces the assembly factor Mrt4. In
      analyzing the role of the P0 carboxyl terminal domain (CTD) during ribosomal
      stalk assembly, we found that its complete removal yields a protein that is
      functionally similar to Mrt4, whereas a chimeric Mrt4 containing the P0 CTD
      behaves more like P0. Deleting the P0 binding sites for the P1 and P2 proteins
      provoked the nuclear accumulation of P0DeltaAB induced by either leptomycin B
      mediated blockage of nuclear export or Mrt4 deletion. This effect was reversed by
      removing P1/P2 from the cell, whereas nuclear accumulation was restored on
      reintroduction of these proteins. Together, these results indicate that the CTD
      determines the function of the P0 in stalk assembly. Moreover, they indicate that
      in cells lacking Mrt4, P0 and its stalk base partner, the L12 protein, bind to
      pre-ribosomes in the nucleus, a complex that is then exported to the cytoplasm by
      a mechanism assisted by the interaction with P1/P2 proteins. Furthermore, in wild
      type cells, the presence of nuclear pre-ribosome complexes containing P0 but not
      L12 is compatible with the existence of an alternative stalk assembly process. 

PMID- 23880661
TI  - Clinical application of in vivo treatment delivery verification based on PET/CT
      imaging of positron activity induced at high energy photon therapy.
AB  - The purpose of this study was to investigate in vivo verification of radiation
      treatment with high energy photon beams using PET/CT to image the induced
      positron activity. The measurements of the positron activation induced in a
      preoperative rectal cancer patient and a prostate cancer patient following 50 MV
      photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were
      delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for
      30 min, starting 7 min after the end of the treatment. The CT volume from the
      PET/CT and the treatment planning CT were coregistered by matching anatomical
      reference points in the patient. The treatment delivery was imaged in vivo based
      on the distribution of the induced positron emitters produced by photonuclear
      reactions in tissue mapped on to the associated dose distribution of the
      treatment plan. The results showed that spatial distribution of induced activity
      in both patients agreed well with the delivered beam portals of the treatment
      plans in the entrance subcutaneous fat regions but less so in blood and oxygen
      rich soft tissues. For the preoperative rectal cancer patient however, a 2 +/-
      (0.5) cm misalignment was observed in the cranial-caudal direction of the patient
      between the induced activity distribution and treatment plan, indicating a beam
      patient setup error. No misalignment of this kind was seen in the prostate cancer
      patient. However, due to a fast patient setup error in the PET/CT scanner a
      slight mis-position of the patient in the PET/CT was observed in all three
      planes, resulting in a deformed activity distribution compared to the treatment
      plan. The present study indicates that the induced positron emitters by high
      energy photon beams can be measured quite accurately using PET imaging of
      subcutaneous fat to allow portal verification of the delivered treatment beams.
      Measurement of the induced activity in the patient 7 min after receiving 5 Gy
      involved count rates which were about 20 times lower than that of a patient
      undergoing standard (18)F-FDG treatment. When using a combination of short lived
      nuclides such as (15)O (half-life: 2 min) and (11)C (half-life: 20 min) with low
      activity it is not optimal to use clinical reconstruction protocols. Thus, it
      might be desirable to further optimize reconstruction parameters as well as to
      address hardware improvements in realizing in vivo treatment verification with
      PET/CT in the future. A significant improvement with regard to (15)O imaging
      could also be expected by having the PET/CT unit located close to the radiation
      treatment room.

PMID- 23880662
TI  - [Gynaecology and obstetrics residency program: is it compatible with labour
      law?].

PMID- 23880663
TI  - Biophysical and formulation studies of the Schistosoma mansoni TSP-2
      extracellular domain recombinant protein, a lead vaccine candidate antigen for
      intestinal schistosomiasis.
AB  - A candidate vaccine to prevent human schistosomiasis is under development. The
      vaccine is comprised of a recombinant 9 kDa antigen protein corresponding to the
      large extracellular domain of a tetraspanin surface antigen protein of
      Schistosoma mansoni, Sm-TSP-2. Here, we describe the biophysical profile of the
      purified, recombinant Sm-TSP-2 produced in the yeast PichiaPink, which in
      preclinical studies in mice was shown to be an effective vaccine against
      intestinal schistosomiasis. Biophysical techniques including circular dichroism,
      intrinsic and extrinsic fluorescence and light scattering were employed to
      generate an empirical phase diagram, a color based map of the physical stability
      of the vaccine antigen over a wide range of temperatures and pH. From these
      studies a pH range of 6.0-8.0 was determined to be optimal for maintaining the
      stability and conformation of the protein at temperatures up to 25  degrees C.
      Sorbitol, sucrose and trehalose were selected as excipients that prevented
      physical degradation during storage. The studies described here provide guidance
      for maximizing the stability of soluble recombinant Sm-TSP-2 in preparation of
      its further development as a vaccine.

PMID- 23880665
TI  - STUB1/CHIP is required for HIF1A degradation by chaperone-mediated autophagy.
AB  - The transcription factor HIF1 is mostly regulated by the oxygen-dependent
      proteasomal degradation of the labile subunit HIF1A. Recent data showed
      degradation of HIF1A in the lysosome through chaperone-mediated autophagy (CMA).
      However the molecular mechanism involved has not been elucidated. This study
      shows that the KFERQ-like motif, that has been identified in all CMA substrates,
      is required to mediate the interaction between HIF1A and the chaperone HSPA8.
      Moreover, mutations in the KFERQ-like motif of HIF1A preclude the interaction
      with the CMA receptor LAMP2A, thus inhibiting its lysosomal degradation.
      Importantly, we show for the first time that the ubiquitin ligase STUB1 is
      required for degradation of HIF1A in the lysosome by CMA. Indeed, mutations in
      STUB1 that inhibit either the ubiquitin ligase activity or its ability to bind to
      HSPA8, both prevent degradation of HIF1A by CMA. Moreover, we show that HIF1A
      binds to and is translocated into intact lysosomes isolated from rat livers. This
      new pathway for degradation of HIF1A does not depend on the presence of oxygen
      and is activated in response to nutrient deprivation such that the levels of
      HIF1A bound to CMA positive lysosomes significantly increase in starved animal
      livers and the binding of HIF1A to LAMP2A increases in response to serum
      deprivation. Moreover, excessive degradation of HIF1A by CMA compromises cells'
      ability to respond to and survive under hypoxia, suggesting that this pathway
      might be of pathophysiological importance in conditions that combine hypoxia with
      starvation. 

PMID- 23880664
TI  - Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4
      activity in GnRH regulation by GT1-7 cells.
AB  - Reproduction is integrated by interaction of neural and hormonal signals
      converging on hypothalamic neurons for controlling gonadotropin-releasing hormone
      (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous
      agonist for the GRP54 receptor, plays a key role in the regulation of GnRH
      secretion. In the present study, we investigated the interaction between
      kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse
      hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA
      expression and GnRH protein production in a concentration-dependent manner. The
      expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation.
      Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4
      action being the most potent for suppressing the kisspeptin effect. The
      expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect
      was reversed in the presence of kisspeptin. It was also revealed that BMP-induced
      Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory
      Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54
      expression, while kisspeptin increased the expression levels of ERalpha and
      ERbeta, suggesting that the actions of estrogen and kisspeptin are mutually
      enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling,
      and ERK signaling was functionally involved in the kisspeptin-induced GnRH
      expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by
      reducing ERK signaling activity. Collectively, the results indicate that the axis
      of kisspeptin-induced GnRH production is bi-directionally controlled, being
      augmented by an interaction between ERalpha/beta and GPR54 signaling and
      suppressed by BMP-4 action in GT1-7 neuron cells. 

PMID- 23880666
TI  - Single blastomere expression profiling of Xenopus laevis embryos of 8 to 32-cells
      reveals developmental asymmetry.
AB  - We have measured the expression of 41 maternal mRNAs in individual blastomeres
      collected from the 8 to 32-cell Xenopus laevis embryos to determine when and how
      asymmetry in the body plan is introduced. We demonstrate that the asymmetry along
      the animal-vegetal axis in the oocyte is transferred to the daughter cells during
      early cell divisions. All studied mRNAs are distributed evenly among the set of
      animal as well as vegetal blastomeres. We find no asymmetry in mRNA levels that
      might be ascribed to the dorso-ventral specification or the left-right axis
      formation. We hypothesize that while the animal-vegetal asymmetry is a
      consequence of mRNA gradients, the dorso-ventral and left-right axes
      specifications are induced by asymmetric distribution of other biomolecules,
      probably proteins. 

PMID- 23880667
TI  - Evaluation of window-tinting films for sunlight phototherapy.
AB  - We evaluated nine semi-transparent plastic window-tinting films for their ability
      to block ultraviolet A (UVA) and infrared (IR) radiation and transmit therapeutic
      blue light (400-520 nm) for treating jaundiced newborns. For indoor testing,
      three light sources (TL/52 special blue fluorescent, Black Light UVA and IR heat
      lamps) were positioned above each film and measured successively using a
      thermocouple thermometer, UVA radiometer and blue light irradiance meter, placed
      below each film. For outdoor testing, the same setup was used with the sun at
      zenith and a cloudless sky. Compared with unfiltered radiation, blue light
      transmission through films ranged from 24 to 83%, UVA transmission was 0.1-7.1%
      and reductions in IR heat were 6-12 degrees C and 5-10 degrees C for heat lamp
      and sun, respectively. The data suggest that most of the relatively low-cost
      window-tinting films tested can effectively reduce sunlight UV and IR and offer a
      range of significant attenuations of therapeutic blue light. 

PMID- 23880668
TI  - Surviving the ICU does not mean that the war is over.

PMID- 23880669
TI  - Ventilator-associated tracheobronchitis and ventilator-associated pneumonia:
      truth vs myth.

PMID- 23880670
TI  - Empiric postoperative autotitrating positive airway pressure therapy: generating
      evidence in the perioperative care of patients at risk for obstructive sleep
      apnea.

PMID- 23880672
TI  - Point: Should board certification be required for sleep test interpretation? Yes.

PMID- 23880673
TI  - Counterpoint: should board certification be required for sleep test
      interpretation? No.

PMID- 23880674
TI  - Rebuttal from Dr Fleishman et al.

PMID- 23880675
TI  - Rebuttal from Dr Simon.

PMID- 23880676
TI  - Rare diseases research: expanding collaborative translational research
      opportunities.
AB  - Extensive public-private partnerships, including the National Institutes of
      Health (NIH) and the rare diseases community, which is seeing a renewed industry
      interest in smaller niche markets, have resulted in an increase of interventions
      for rare diseases. Significant collaborative efforts are required among the
      pharmaceutical industry, foundations, patient-advocacy groups, academic and
      government investigators and funding programs, regulatory scientists, and
      reimbursement agencies to meet the unmet diagnostic and treatment needs for
      approximately 25 million people in the United States with 7,000 rare diseases.
      The expanding role and outreach activities of patient-advocacy groups have
      increased public awareness. In the United States, a rare disease is defined as a
      disorder or condition with a prevalence of <200,000 people. In 2011, the NIH
      provided >$3.5 billion for rare diseases research, including $750 million for
      orphan product development activities, nearly 11.4% of the NIH research budget.
      Several research institutes and centers of the NIH, including the National Center
      for Advancing Translational Sciences, have initiated varied translational
      research efforts to address the absence of preclinical and clinical data required
      for regulatory review purposes. Clinicians can expect to see significant
      increases in requests from patients and their families to participate in patient
      registries and natural history or observational studies to gather specific
      information from a larger pool of patients on the progression of the disease or
      response to treatments. An expanding emphasis on rare diseases provides hope for
      the millions of patients with rare diseases.

PMID- 23880677
TI  - Oxidative stress in COPD.
AB  - Oxidative stress is now recognized as a major predisposing factor in the
      pathogenesis of COPD. Existing therapies for COPD are ineffective at halting
      disease progression, with bronchodilators being the mainstay of pharmacotherapy,
      providing symptomatic relief only. It is, therefore, important for a better
      understanding of the underlying mechanisms by which oxidative stress drives
      disease pathogenesis to develop novel and more effective therapies. Antioxidant
      capacity in COPD is substantially reduced as a result of cigarette smoking and
      exacerbations, with oxidative stress persisting long after the cessation of
      cigarette smoking or exacerbation, due to the continued production of reactive
      oxygen species from endogenous sources. We discuss (1) how oxidative stress
      arises in the lung, (2) how it is neutralized, (3) what genetic factors may
      predispose to the development of COPD, and (4) how this impacts inflammation and
      autoimmunity in the development of emphysema and small airways disease. Finally,
      various strategies have been considered to neutralize the increased oxidative
      burden present in COPD. This review highlights why current antioxidant strategies
      have so far failed and what promising alternatives are on the horizon. Moreover,
      a number of studies have shown that there is no single "magic bullet" to combat
      oxidative stress, but instead a combination therapy, targeting oxidative stress
      in the various subcellular compartments, may prove to be more effective in COPD. 

PMID- 23880678
TI  - Biomarkers in pulmonary hypertension: what do we know?
AB  - Pulmonary hypertension (PH) is a hemodynamic condition that has a poor prognosis
      and can lead to right-sided heart failure. It may result from common diseases
      such as left-sided heart or lung disease or may present as the rare entity of
      idiopathic pulmonary arterial hypertension. Biomarkers that specifically indicate
      the pathologic mechanism, the severity of the disease, and the treatment response
      would be ideal tools for the management of PH. In this review, markers related to
      heart failure, inflammation, hemostasis, remodeling, and endothelial cell-smooth
      muscle cell interaction are discussed, and their limitations are emphasized.
      Anemia, hypocarbia, elevated uric acid, and C-reactive protein levels are
      unspecific markers of disease severity. Brain natriuretic peptide and N-terminal
      fragment of pro-brain natriuretic peptide have been recommended in current
      guidelines, whereas other prognostic markers, such as growth differentiation
      factor-15, osteopontin, and red cell distribution width, are emerging. Chemokines
      of the CC family and matrix metalloproteases have been linked to the vascular
      pathologic mechanisms, and new markers such as apelin have been described.
      Circulating endothelial and progenitor cells have received much attention as
      markers of disease activity, but with controversial findings. A lack of standards
      for cell isolation and characterization methods and differences in the pathologic
      mechanisms of the investigated patients may have contributed to the
      discrepancies. In conclusion, although several promising markers have been
      identified over the past few years, the development of more specific markers,
      standardization, and prospective validation are warranted. 

PMID- 23880679
TI  - Medical malpractice reform measures and their effects.
AB  - New rules and methods for medical injury dispute resolution have been launched in
      New Hampshire and New York, and demonstration projects are underway elsewhere.
      This article describes major medical malpractice reforms undertaken and proposed
      in recent years. Reforms are classified as (1) liability-limiting initiatives
      favoring health-care providers; (2) procedural innovations promoted as improving
      dispute resolution processes, such as patient compensation funds, "sorry" laws,
      disclosure and early offer laws, health courts, and safe harbor laws; and (3)
      major conceptual reforms to move liability away from physicians to hospitals or
      administrative no-fault compensation systems. Empirical evidence about the
      practical effects of already-implemented reforms, such as damage caps, is
      reviewed. In light of declining malpractice claim rates, heavier adverse impacts
      of damage caps on vulnerable groups (people who have severe injuries, who are
      elderly, and who are unemployed) and repeated findings of state law
      unconstitutionality, the rationale for nationwide damage caps is questioned.
      Attention to innovative reform proposals such as patient compensation funds,
      disclosure and early offer laws, safe harbor laws, enterprise insurance and no
      fault compensation systems, is encouraged. 

PMID- 23880680
TI  - Recognizing laboratory cross-contamination: two false-positive cultures of
      Mycobacterium tuberculosis--Oklahoma, 2011.
AB  - Mycobacterium tuberculosis (MTB) isolation from clinical specimens is the
      standard for TB diagnosis. Positive MTB cultures are rarely questioned, but false
      positive culture rates range from 2% to 4%. In December 2011, two smear-negative,
      culture-positive TB cases were reported to the Oklahoma State Department of
      Health (OSDH) in people without TB signs or symptoms. OSDH TB control officers
      interviewed physicians and laboratory personnel, reviewed patient charts, traced
      epidemiologic links, and performed microbiologic studies to determine if these
      were true TB cases. Both specimens were found to have been processed on the same
      day, at the same laboratory, under the same hood, and by the same technician
      sequentially after a strongly smear-positive TB specimen. No epidemiologic links
      were identified among the three patients. Spoligotyping and 24-locus
      mycobacterial interspersed repetitive unit typing of the three specimens were
      identical. Only liquid media grew MTB in the two questionable specimens. A
      laboratory splash incident was suspected, whereby all three liquid media sample
      lids were open during inoculation rather than being opened one at a time, causing
      cross-contamination. Also, the two specimens were incubated for 2-3 weeks longer
      than standard protocol before MTB growth was observed. Patient 1 was not treated
      for TB because her physician doubted the culture result. Patient 2, an organ
      transplant recipient, began four-drug anti-TB therapy, and an investigation was
      initiated for transplant-associated TB. Adherence to strict laboratory techniques
      and recognizing the possibility of false-positive MTB cultures, especially when
      inconsistent with clinical data, are essential in preventing erroneous TB
      diagnoses. 

PMID- 23880681
TI  - A case of hut lung: scanning electron microscopy with energy dispersive x-ray
      spectroscopy analysis of a domestically acquired form of pneumoconiosis.
AB  - Hut lung is a pneumoconiosis caused by exposure to smoke derived from biomass
      fuels used for cooking in poorly ventilated huts. We report, to our knowledge,
      the first analysis of the dust deposited in the lungs in hut lung by scanning
      electron microscopy with energy dispersive x-ray spectroscopy (SEM/EDS). A
      Bhutanese woman presented with shortness of breath and an abnormal chest
      radiograph. Chest CT scan showed innumerable tiny bilateral upper lobe
      centrilobular nodules. Transbronchial biopsy revealed mild interstitial fibrosis
      with heavy interstitial deposition of black dust. SEM/EDS showed that the dust
      was carbonaceous, with smaller yet substantial numbers of silica and silicate
      particles. Additional history revealed use of a wood/coal-fueled stove in a
      small, poorly ventilated hut for 45 years. The possibility of hut lung should be
      considered in women from countries where use of biomass-fueled stoves for cooking
      is common. Our findings support the classification of this condition as a mixed
      dust pneumoconiosis. 

PMID- 23880683
TI  - Perioperative risk and management in patients with pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is a known risk factor for perioperative
      complications. Unlike in the case of cardiac surgery, PH is currently not listed
      as an independent risk factor for postoperative complications in guidelines for
      the management of noncardiac surgery. Despite the paucity of data, though,
      patients with PH are often counseled against having elective procedures because
      early and sudden postoperative deaths have been reported. Patients with PH are
      unable to accommodate alterations in right ventricular (RV) preload or afterload
      induced by fluid shifts, medications, or changes in the autonomic nervous system
      precipitated by hypoxia or hypercapnia. These factors become magnified in
      situations of added stress such as surgical intervention. Systemic hypotension
      and arrhythmias may precipitate RV ischemia, further worsening RV function.
      Patient and surgical characteristics and choice of anesthetic technique are
      crucial factors in perioperative management. The two main principles of
      perioperative management are the prevention of systemic hypotension (risk of RV
      ischemia) and the prevention of acute elevations in pulmonary arterial pressure
      (risk of RV failure). Close monitoring, optimization of systemic BP, pain
      control, oxygenation and ventilation, avoidance of exacerbating factors, and use
      of vasopressors and pulmonary vasodilators as necessary are essential elements of
      management. Understanding the pathophysiology, cause, and severity of PH in the
      individual perioperative patient allows accurate risk assessment, optimization of
      PH and RV function prior to surgery, and appropriate intraoperative and
      postoperative management. 

PMID- 23880682
TI  - Fatal association of mechanical valve thrombosis with dabigatran: a report of two
      cases.
AB  - Several new oral anticoagulants have been approved for thromboembolism prevention
      in patients with nonvalvular atrial fibrillation. However, they are not yet
      approved for anticoagulation use in patients with prosthetic mechanical valves,
      and no randomized data have been published so far on their safety of use in these
      patients. We present two cases of patients with prosthetic mechanical mitral
      valves who were switched from warfarin and acenocoumarol to dabigatran and within
      1 month experienced severe valve complications resulting in death. One patient
      experienced stroke and later cardiogenic shock and death, and the other
      experienced pulmonary edema, cardiogenic shock, and subsequent death. 

PMID- 23880684
TI  - Adult with recurrent chest pain and vomiting. Diagnosis: Esophageal duplication
      cyst.

PMID- 23880685
TI  - A 57-year-old woman with obesity, respiratory insufficiency, and slowed mental
      state. Diagnosis: Obesity hypoventilation syndrome.

PMID- 23880686
TI  - A rare case of empyema. Answer: Transformation of CLL into diffuse large B-cell
      lymphoma, also known as Richter syndrome.

PMID- 23880688
TI  - Nocturnal intermittent hypoxemia and metabolic dyslipidemia.

PMID- 23880689
TI  - Response.

PMID- 23880690
TI  - Statins reduce lung inflammation by promoting the clearance of particulate matter
      from lung tissues.

PMID- 23880691
TI  - Routine pneumocystis pneumonia prophylaxis in patients treated with rituximab?

PMID- 23880692
TI  - Response.

PMID- 23880693
TI  - Pathophysiology of intrapulmonary right-to-left shunt in infants with obstructive
      apnea.

PMID- 23880694
TI  - An algorithm for approaching mediastinal lymphadenopathy in pulmonary
      hypertension.

PMID- 23880695
TI  - Response.

PMID- 23880696
TI  - Air pollution and chronic cough in China.

PMID- 23880697
TI  - Response.

PMID- 23880698
TI  - A patient with lung cancer presenting with respiratory failure and shock.

PMID- 23880699
TI  - Role of support measures and palliative care.
AB  - PURPOSE OF REVIEW: The care of patients with idiopathic pulmonary fibrosis is
      challenging at a time when there are no medications with proven efficacy in
      extending patient survival or quality of life. However, a number of recent
      studies suggest that patients participating in clinical trials including the
      placebo arm have improved outcome. This suggests that there are elements of
      supportive care which may prove beneficial to IPF patients. Further, control of
      patient symptoms should be a critical goal in care of patients with IPF. RECENT
      FINDINGS: A number of both pharmacologic and nonpharmacologic therapies are
      available to reduce symptoms in patients with IPF. These include low-dose
      narcotics, pulmonary rehabilitation and oxygen therapy. Further, addressing
      issues of depression may be beneficial for symptom management. Palliative care
      can and should be more fully integrated in the care of patients with IPF.
      SUMMARY: Incorporating supportive and palliative measures in the care of patients
      with IPF may improve both quality of life and survival, but far more research is
      needed in this fledgling field.

PMID- 23880700
TI  - Common variable immunodeficiency-associated granulomatous and interstitial lung
      disease.
AB  - PURPOSE OF REVIEW: Common variable immunodeficiency (CVID) is the most common
      primary immunodeficiency characterized by a deficiency of immunoglobulins.
      Approximately 30% of the patients develop autoimmune and granulomatous disease.
      Similar to sarcoidosis, granulomatous disease in CVID can potentially affect all
      organs, but the lung is the most common. Interstitial lung disease (ILD)
      manifests in 5-15% of CVID patients, and is present already at the initial
      diagnosis in the majority of patients. The number of published studies addressing
      ILD in CVID is limited. However, recently, several studies added substantial
      knowledge to the field and are discussed within this review in the context of the
      literature. RECENT FINDINGS: Histologically, ILD in CVID presents within the
      known patterns of sarcoid-like granuloma, organizing pneumonia, lymphocytic
      interstitial pneumonitis and nonspecific interstitial pneumonia. Often, these
      patterns are concomitantly found in the same patients. Three new articles were
      published which analyzed high-resolution computed tomography findings and
      response to treatment. SUMMARY: In a considerable number of patients, ILD is
      stable over years and patients may not need any immunosuppressive treatment.
      Prednisone treatment is often used as the first-line treatment and studies
      suggest response to treatment in 50-66% of cases. In progressive disease with
      lung function impairment, combined immunosuppressive treatment is recommended.

PMID- 23880701
TI  - Diagnosis of pulmonary sarcoidosis.
AB  - PURPOSE OF REVIEW: To summarize and highlight recent advances in the field of the
      diagnosis of pulmonary sarcoidosis. RECENT FINDINGS: Several techniques have
      emerged as important tools in the context of a clinical and radiological
      situation compatible with pulmonary sarcoidosis. Among them, computed tomography
      (CT) scan can not only exhibit characteristic imaging, but also contribute to an
      increased yield of tissue sampling through transbronchial biopsies. CT is also
      essential to the detection of mediastinal lymphadenopathy as potential targets of
      endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA). The
      latter is a well-tolerated and highly sensitive procedure which might become the
      first-line diagnostic tool in sarcoid patients with hilar or mediastinal lymph
      nodes. 18F deoxy-fluoro-glucose (18F-FDG) PET has a remarkable sensitivity in the
      detection of occult sites of the disease and a high value in guiding biopsy to
      these active sites. A combined imaging modality using both F-FDG PET and CT scan,
      more sensitive than PET alone, is now the standard of care in patients requiring
      histological sampling of active lesions. SUMMARY: The finding of noncaseating
      granulomas remains crucial to the diagnosis of sarcoidosis. The methods described
      here markedly enhance the diagnostic yield of tissue sampling along with low
      risks of complications.

PMID- 23880702
TI  - Multinational evidence-based World Association of Sarcoidosis and Other
      Granulomatous Disorders recommendations for the use of methotrexate in
      sarcoidosis: integrating systematic literature research and expert opinion of
      sarcoidologists worldwide.
AB  - PURPOSE OF REVIEW: Although glucocorticosteroids are considered the first-line
      treatment in sarcoidosis, refractory cases require alternatives, such as
      methotrexate (MTX). The aim of this study was to develop, on behalf of the World
      Association of Sarcoidosis and Other Granulomatous Disorders (WASOG),
      multinational evidence-based recommendations for the use of MTX in sarcoidosis
      for routine clinical practice. RECENT FINDINGS: A systematic literature search
      was conducted and combined with the opinions of sarcoidosis experts worldwide to
      formulate the recommendations. An online survey concerning 10 clinical questions
      was sent through the WASOG newsletter to sarcoidosis experts. Agreement about the
      recommendations amongst the world's leading sarcoidologists was evaluated. A
      total of 237 articles were identified, 43 of which were included. Randomized
      controlled trial evidence supporting the use of MTX in sarcoidosis was limited.
      Forty-five per cent (113 of 250) of the sarcoidosis experts contacted completed
      the survey (Europe 55%, North America 26% and Asia 12%). Ten recommendations were
      formulated concerning the indications for use, starting dose, folic acid, work
      up, contraindications, monitoring, administration options in case of adverse
      gastrointestinal effects, hepatotoxicity, long-term safety and use during
      pregnancy and breast feeding. SUMMARY: Ten multinational evidence-based
      recommendations for the use of MTX in sarcoidosis were developed, which are
      supported by the world's foremost sarcoidosis experts.

PMID- 23880703
TI  - Cardiac sarcoidosis.
AB  - PURPOSE OF REVIEW: Heart involvement during sarcoidosis is a medical emergency.
      The review focuses on published data analysis of clinical management and therapy
      involving a multidisciplinary monitoring of cardiac sarcoidosis. RECENT FINDINGS:
      With the emergence of new modalities, especially MRI and FDG PET scan, cardiac
      sarcoidosis is most often suspected and confirmed even in atypical cases.
      Laboratory investigations may help to diagnose and survey. Cardiac sarcoidosis
      drastically changes functional and vital prognosis. Recent studies define earlier
      detrimental predictable criteria to underline how beneficial is the combination
      of immunosuppressive therapy and cardiac treatment to patients. There are no
      large prospective studies, but case reports and small series support an
      appropriate therapeutic approach, which includes corticosteroids and
      immunosuppressive agents. SUMMARY: Our review illustrates the importance of
      looking for cardiac sarcoidosis in all sarcoidosis patients and to propose more
      specific and sensitive investigations when suspected on clinical and/or
      electrical signs. It emphasizes the need for more adapted criteria and even more
      prognostic criteria to choose the best therapeutic option.

PMID- 23880704
TI  - Electrophysiologic manifestations of cardiac sarcoidosis.
AB  - PURPOSE OF REVIEW: Cardiac involvement in sarcoidosis patients is frequently
      unrecognized with ventricular arrhythmias and sudden cardiac death (SCD)
      sometimes occurring as its initial presentation. Early involvement of an
      electrophysiologist as part of a multidisciplinary team is essential to
      screening, risk stratification, and management of cardiac sarcoidosis patients.
      This review outlines potential manifestations of cardiac sarcoidosis, as well as
      diagnostic and treatment strategies. RECENT FINDINGS: Recent retrospective
      analyses have shown that the incidence of atrioventricular block, atrial
      tachyarrhythmias, and ventricular tachyarrhythmias in these patients is
      substantial. In addition to advanced cardiac imaging, there is a role for ECG,
      signal-averaged ECG, ambulatory telemetry monitoring, and electrophysiologic
      testing in the initial evaluation of a patient with suspected cardiac
      sarcoidosis. There have been recent investigations into the role of implantable
      cardioverter-defibrillators (ICDs) for SCD prevention with a high rate of
      appropriate therapies observed. Immunosuppressive therapy, antiarrhythmic drugs,
      and catheter ablation each also have a role in the reduction of overall
      arrhythmic burden. SUMMARY: The electrophysiologist's approach to a patient with
      cardiac sarcoidosis can aid in diagnosis, risk stratification, and management
      with antiarrhythmic therapy, catheter ablation, and ICD implantation for the
      prevention of SCD.

PMID- 23880705
TI  - Imaging techniques in chronic thromboembolic pulmonary hypertension.
AB  - PURPOSE OF REVIEW: Chronic thromboembolic pulmonary hypertension (CTEPH) can
      affect up to 4-5% of patients with acute pulmonary embolism. It is likely an
      underdiagnosed entity. Misdiagnosis is common because patients often present with
      nonspecific symptoms of pulmonary hypertension. Early diagnosis may help improve
      the outcome, as CTEPH is potentially curable with pulmonary thromboendarterectomy
      (PEA). Imaging is central to an accurate diagnosis, and for assessing correctly
      the technical feasibility of PEA. This review examines the findings of various
      imaging techniques in CTEPH and their contribution in the diagnostic and
      therapeutic evaluation of the disease. RECENT FINDINGS: Ventilation-perfusion
      scintigraphy remains a sensitive method for excluding CTEPH. Multidetector
      computed tomography angiography (MDCTA) depicts directly changes of CTEPH,
      provides a surgical 'road map', and should be used for the diagnostic assessment
      of all suitable patients with pulmonary arterial hypertension. In many centers,
      the role of conventional pulmonary angiography is gradually being replaced by
      cross-sectional methods. MRI has a role in preoperative and postoperative
      assessment of right ventricular function and can depict vascular abnormalities up
      to segmental level. SUMMARY: MDCTA in combination with MRI represent the main
      techniques for the diagnosis and management of CTEPH. Newer techniques such as
      dual spectrum computed tomography may further improve preoperative and
      postoperative assessment of CTEPH patients.

PMID- 23880706
TI  - Iodine recycling via 1,3-migration in iodoindoles under metal catalysis.
AB  - 3-Substituted (indol-2-yl)-alpha-allenols show divergent patterns of reactivity
      under metal catalysis. An unprecedented intramolecular 1,3-iodine migration is
      described. 

PMID- 23880707
TI  - Phthalates and parabens in personal care products from China: concentrations and
      human exposure.
AB  - Our previous studies showed that populations in China are widely exposed to
      phthalates and parabens. Nevertheless, sources of Chinese exposure to phthalates
      and parabens are not well understood. In this study, we measured concentrations
      of nine phthalates and six parabens in five categories of personal care products
      (PCPs, N = 52) collected from Tianjin, China, and estimated human exposure doses
      to these compounds. The most frequently detected phthalates and parabens in PCPs
      were diethyl phthalate (DEP) (detection frequency 54 %), methyl paraben (MeP),
      and n-propyl paraben (PrP) (~75 %). The concentrations of DEP in PCPs ranged from
      not detected (ND; <0.1 MUg/g) to 937 MUg/g. The highest concentrations of MeP and
      PrP were 2,826 and 1,564 MUg/g, respectively. Median exposure dose to parabens
      through dermal application of PCPs in China was estimated at 18,700 MUg/d, which
      was two orders of magnitude greater than that calculated for phthalates (45.5
      MUg/d). Hand and body lotions were the major contributors to exposures, and the
      daily exposure doses for DEP, MeP, and PrP from these products were 38.4, 10,200
      and 4,890 MUg, respectively. 

PMID- 23880708
TI  - Mid-term variation of vertical distribution of acid volatile sulphide and
      simultaneously extracted metals in sediment cores from Lake Albufera (Valencia,
      Spain).
AB  - Lake Albufera is one of the most eutrophic bodies of water in Spain due to point
      and diffuse pollution over past decades, and its sediments are likely to be
      anoxic because of high organic matter flux. Hence, sulphides can play an
      important role in limiting the mobility of heavy metals. This study aimed to
      study the vertical variation of acid volatile sulphide (AVS) and simultaneously
      extracted metals (SEM) in sediment cores collected from Lake Albufera; other
      sediment characteristics, such as organic matter, biochemical oxygen, demand or
      total metals, were also studied. Three sites were selected, and four sampling
      campaigns were performed to study spatial and temporal variation as well as to
      obtain information regarding historical variation in the composition of
      sediments. AVS and SEM were analysed by the purge-and-trap method. The vertical
      distribution of AVS and SEM varied depending on the sampling site-concentrations
      of AVS and SEM were higher at sites close to mouths of inflowing channels. A
      decreasing trend of AVS has been found at these sites over time: In the two first
      samplings, AVS increased with depth reaching maximum concentrations of 40 and 21
      MUmol g(-1), but from then on AVS were lower and decreased with depth. SEM
      decreased with depth from 3 MUmol g(-1) in surface layers to approximately 1
      MUmol g(-1) at deeper segments at these sites. However, the central site was more
      uniform with respect to depth as well as with time; it presented lower values of
      SEM and AVS (mean 0.9 and 2.0 MUmol g(-1) respectively), and the maximum value of
      AVS (7 MUmol g(-1)) was found at the top layer (0-3 cm). According to the (SEM
      AVS)/fOC approach, every site, and throughout the cores, can be classified as
      containing nontoxic metals because the values were <130 MUmol g(-1). 

PMID- 23880710
TI  - Letter from the editor.

PMID- 23880709
TI  - Structural and magnetic studies of the electron doped manganites Sr0.65Pr0.35
      xCexMnO3 (0.00 <= x <= 0.35).
AB  - The nuclear and magnetic structures and properties of Sr0.65Pr0.35-xCexMnO3 (0.00
      <= x <= 0.35) were investigated using a combination of synchrotron x-ray and
      neutron powder diffraction, along with magnetic and x-ray absorption near edge
      structure measurements. At room temperature, doping with Ce results in a
      transition from a tetragonal structure in I4/mcm to an orthorhombic one in Imma
      associated with the loss of long range orbital ordering. At low temperatures, we
      observe the formation of an orthorhombic Fmmm phase. XANES measurements
      demonstrate that the Ce exists as a mixture of Ce(3+) and Ce(4+). 

PMID- 23880711
TI  - Efficacy of bisphosphonates and other bone-targeted agents in metastatic bone
      disease from solid tumors other than breast and prostate cancers.
AB  - Metastatic bone disease complicates the course of malignancy in a substantial
      proportion of patients with advanced cancer. Bisphosphonates are now widely used
      to improve skeleton-related outcomes of patients with metastatic cancer to the
      bone. Most studies evaluating the efficacy of bisphosphonates and other bone
      targeted agents have been performed in patients with metastatic breast and
      prostate cancer. Only a few studies have evaluated the role of bisphosphonates in
      other tumor types involving the skeletal system. We present a review of the
      clinical literature focusing on the current and potential roles of
      bisphosphonates (particularly zoledronic acid) and newer bone-targeted therapies
      in patients with metastasis to bone arising from solid tumors other than breast
      and prostate cancer. 

PMID- 23880712
TI  - Efficacy of neoadjuvant cisplatin and oral capecitabine in triple-negative breast
      cancers: a pilot study.
AB  - Due to the lack of molecular targets, triple-negative breast cancers (TNBCs)
      typically represent a worse prognosis compared to their hormone-positive
      counterparts. While neoadjuvant chemotherapy has been used for breast cancers for
      a long time, there is no standard chemotherapy regimen for TNBCs. Cisplatin has
      generally been regarded as an effective chemotherapy agent against TNBCs.
      However, here we present a pilot study involving the use of cisplatin in
      combination with oral capecitabine in the neoadjuvant setting in 16 patients with
      TNBC. Twelve patients were African American and 4 patients were white. Six
      patients completed all 4 cycles of chemotherapy, 6 patients completed 3 cycles,
      and 4 patients completed 2 cycles. A complete clinical response was observed in 2
      patients, and 10 patients achieved partial clinical response. One patient had
      progressive disease, and 3 patients were lost to follow-up or taken off study.
      Following chemotherapy, 12 patients underwent surgery (7 patients had breast
      conservation, and 5 patients had a mastectomy). Ten of the 12 patients who had
      surgery achieved a partial pathologic response and the other 2 patients had
      complete pathologic response. Grade 3 nausea, vomiting, and diarrhea occurred in
      7 patients; 1 patient experienced dehydration and renal failure; and 5 patients
      had grade 1/2 hand-foot syndrome. There were no grade 4 or 5 toxicities. The
      response to cisplatin-capecitabine combination chemotherapy in the neoadjuvant
      setting was suboptimal compared to that with single-agent cisplatin in prior
      studies. The toxicity profile with this combination was also worse than that of
      cisplatin alone. Based on our findings, we do not recommend this combination
      regimen in the neoadjuvant setting for TNBCs. However, future studies analyzing
      the use of cisplatin with other combinations are warranted. 

PMID- 23880713
TI  - Update in the management of mantle cell lymphoma.

PMID- 23880714
TI  - Extended treatment of venous thromboembolism.

PMID- 23880715
TI  - Accounting for tumor heterogeneity in the development of predictive biomarkers.

PMID- 23880716
TI  - Fatigue in cancer patients.

PMID- 23880717
TI  - Hypereosinophilic syndrome presenting as an unusual triad of eosinophilia, severe
      thrombocytopenia, and diffuse arterial thromboses, with good response to
      mepolizumab.

PMID- 23880718
TI  - An unusual presentation of idiopathic hypereosinophilic syndrome.

PMID- 23880719
TI  - Reduced-dose carboxypeptidase-G2 successfully lowers elevated methotrexate levels
      in an adult with acute methotrexate-induced renal failure.

PMID- 23880720
TI  - Using a lower dose of glucarpidase to reduce plasma levels of methotrexate.

PMID- 23880721
TI  - Optimization of pulse-field gel electrophoresis for subtyping of Klebsiella
      pneumoniae.
AB  - A total of 110 strains of Klebsiella pneumoniae were used to optimize pulsed
      field gel electrophoresis (PFGE) for subtyping of K. pneumoniae. For optimization
      of electrophoresis parameters (EPs) of XbaI-PFGE, 11 isolates were analyzed with
      XbaI digestion using three EPs. The EP of a switch time of 6 to 36 s for 18.5 h
      gave clearest patterns and was declared the optimal EP for XbaI PFGE of K.
      pneumoniae. By software analysis and pilot study, AvrII was chosen as another
      PFGE enzyme. Both XbaI- and AvrII-PFGE gave D-values higher than 0.99 for 69 K.
      pneumoniae isolated from different sources. Our results also showed good
      typeability, reproducibility of both XbaI- and AvrII-PFGE for K. pneumoniae
      subtyping. Furthermore, the established PFGE method also had good discriminatory
      power to distinguish outbreak K. pneumoniae strains and a high degree of
      consistency with multilocus sequence typing method. A rapid PFGE protocol was
      established here, which could be used for genotyping and other researches of K.
      pneumoniae. 

PMID- 23880722
TI  - A Bayesian approach to estimate the prevalence of Schistosomiasis japonica
      infection in the Hubei Province Lake Regions, China.
AB  - A Bayesian inference model was introduced to estimate community prevalence of
      Schistosomiasis japonica infection based on the data of a large-scale survey of
      Schistosomiasis japonica in the lake region in Hubei Province. A multistage
      cluster random sampling approach was applied to the endemic villages in the lake
      regions of Hubei Province in 2011. IHA test and Kato-Katz test were applied for
      the detection of the S. japonica infection in the sampled population. Expert
      knowledge on sensitivities and specificities of IHA test and Kato-Katz test were
      collected based on a two-round interview. Prevalence of S. japonica infection was
      estimated by a Bayesian hierarchical model in two different situations. In
      Situation 1, Bayesian estimation used both IHA test data and Kato-Katz test data
      to estimate the prevalence of S. japonica. In Situation 2, only IHA test data was
      used for Bayesian estimation. Finally 14 cities and 46 villages from the lake
      regions of Hubei Province including 50,980 residents were sampled. Sensitivity
      and specificity for IHA test ranged from 80% to 90% and 70% to 80%, respectively.
      For the Kato-Katz test, sensitivity and specificity were from 20% to 70% and 90%
      to 100%, respectively. Similar estimated prevalence was obtained in the two
      situations. Estimated prevalence among sampled villages was almost below 13% in
      both situations and varied from 0.95% to 12.26% when only using data from the IHA
      test. The study indicated that it is feasible to apply IHA test only combining
      with Bayesian method to estimate the prevalence of S. japonica infection in large
      scale surveys. 

PMID- 23880723
TI  - Circulating nitrite and nitrate are associated with job-related fatigue in women,
      but not in men.
AB  - A recent study indicated that serum nitrite and nitrate (NOx) is inversely
      associated with general fatigue. The purpose of this study was to confirm the
      negative association between nitric oxide (NO) and fatigue and to examine whether
      NO can prevent fatigue caused by job strain. The subjects, 570 workers (272 men
      and 298 women), answered self-administered questionnaires and underwent a medical
      examination. Job strain was measured using the Job Content Questionnaire. Fatigue
      was evaluated using the Profile of Mood States. Venous blood samples were
      collected after overnight fasting. Plasma NOx concentration was determined by the
      ozone-based chemiluminescence assay. Plasma NOx levels were significantly (p <
      0.05) negatively associated with fatigue even after adjustment for job strain and
      potential confounders in women, but not in men. Significant (p < 0.05)
      interactions showed that, in women, as the level of the job strain worsened,
      fatigue was exacerbated, but the plasma NOx seemed to buffer the association,
      even after adjustment for potential confounders and the interaction between job
      strain and vegetable intake. In women, NO seemed to be inversely associated with
      fatigue and to buffer the association between job strain and fatigue, but not in
      men. 

PMID- 23880724
TI  - Seasonal differences in the day-of-the-week pattern of suicide in Queensland,
      Australia.
AB  - Various temporal patterns of suicide events, according to time of day, day of
      week, month and season, have been identified. However, whether different
      dimensions of time interact has not been investigated. Using suicide data from
      Queensland, Australia, this study aims to verify if there is an interaction
      effect between seasonal and day-of-the-week distribution. Computerized suicide
      data from the Queensland Suicide Register for those aged 15+ years were analyzed
      according to date of death, age, sex and geographic location for the period 1996
      2007. To examine seasonal differences in day-of-the-week pattern of suicide,
      Poisson regressions were used. A total of 6,555 suicides were recorded over the
      whole study period. Regardless of the season, male residents of Brisbane had a
      significantly marked day-of-the-week pattern of suicide, with higher rates
      between Mondays and Thursdays. When seasonal differences were considered, male
      residents in Brisbane showed a Monday peak in summer and a wave-shape pattern
      with a peak on Thursday and a nadir on Saturdays in winter. Whilst males have
      distinctive peaks in terms of days of the week for summer and winter, females do
      not show similar patterns. 

PMID- 23880725
TI  - Development of a monoclonal antibody-based sandwich ELISA for peanut allergen Ara
      h 1 in food.
AB  - We have established a highly sensitive sandwich enzyme-linked immunosorbent assay
      (ELISA) based on two monoclonal antibodies (mAb) to measure the content of the
      major peanut allergen Ara h 1 in foods. Two mAbs were selected out of 12 murine
      hybridoma cells secreting Ara h 1-specific antibody. Using mAb 6 as the capture
      antibody and HRP-labelled mAb 4 as the detection antibody, the limit of detection
      (LOD) the assay was 0.34 ng/mL. Cross-reaction analysis showed that this method
      was strongly specific and had no cross-reactions with Ara h 2, pea protein or soy
      protein. Sample analysis showed that this ELISA was a useful tool to monitor
      peanut allergens in food products by measuring Ara h 1 content. 

PMID- 23880726
TI  - The association of lone-motherhood with smoking cessation and relapse:
      prospective results from an Australian national study.
AB  - The aims were to examine the association of lone-motherhood with smoking
      cessation and relapse, and to investigate the extent to which this association
      was accounted for by socioeconomic status (education, occupation, and income),
      social support, and mental health. We used data from 10 yearly waves (2001 to
      2010) of the Household Income and Labour Dynamics in Australia (HILDA) survey.
      Response rate in the first wave was 66%. Logistic regression was used to examine
      the effect of lone-motherhood and other covariates on smoking cessation (n =
      2,878) and relapse (n = 3,242). Results showed that the age-adjusted odds of
      smoking cessation were 32% smaller among lone mothers than partnered mothers (p =
      0.004). The age-adjusted odds of relapse was 172% greater among lone mothers than
      partnered mothers (p < 0.001). We found that socioeconomic status, social
      support, and mental health account for some of the association of lone motherhood
      and cessation and relapse. While efforts to reduce the smoking prevalence among
      lone mothers should focus on their material deprivation, availability of social
      support, and addressing mental health issues, other factors unique to the lives
      of lone mothers also need to be taken into account. More research is needed to
      discover other factors that can explain the association of lone-motherhood and
      smoking behavior. 

PMID- 23880727
TI  - Estimation of chlorophyll-a concentration in Turbid Lake using spectral smoothing
      and derivative analysis.
AB  - As a major indicator of lake eutrophication that is harmful to human health, the
      chlorophyll-a concentration (Chl-a) is often estimated using remote sensing, and
      one method often used is the spectral derivative algorithm. Direct derivative
      processing may magnify the noise, thus making spectral smoothing necessary. This
      study aims to use spectral smoothing as a pretreatment and to test the
      applicability of the spectral derivative algorithm for Chl-a estimation in Taihu
      Lake, China, based on the in situ hyperspectral reflectance. Data from July
      August of 2004 were used to build the model, and data from July-August of 2005
      and March of 2011 were used to validate the model, with Chl-a ranges of 5.0-156.0
      mg/m3, 4.0-98.0 mg/m3 and 11.4-35.8 mg/m3, respectively. The derivative model was
      first used and then compared with the band ratio, three-band and four-band
      models. The results show that the first-order derivative model at 699 nm had
      satisfactory accuracy (R2 = 0.75) after kernel regression smoothing and had
      smaller validation root mean square errors of 15.21 mg/m3 in 2005 and 5.85 mg/m3
      in 2011. The distribution map of Chl-a in Taihu Lake based on the HJ1/HSI image
      showed the actual distribution trend, indicating that the first-order derivative
      model after spectral smoothing can be used for Chl-a estimation in turbid lake. 

PMID- 23880728
TI  - Modeling monthly variation of Culex tarsalis (Diptera: Culicidae) abundance and
      West Nile Virus infection rate in the Canadian Prairies.
AB  - The Canadian prairie provinces of Alberta, Saskatchewan, and Manitoba have
      generally reported the highest human incidence of West Nile virus (WNV) in
      Canada. In this study, environmental and biotic factors were used to predict
      numbers of Culex tarsalis Coquillett, which is the primary mosquito vector of WNV
      in this region, and prevalence of WNV infection in Cx. tarsalis in the Canadian
      prairies. The results showed that higher mean temperature and elevated time
      lagged mean temperature were associated with increased numbers of Cx. tarsalis
      and higher WNV infection rates. However, increasing precipitation was associated
      with higher abundance of Cx. tarsalis and lower WNV infection rate. In addition,
      this study found that increased temperature fluctuation and wetland land cover
      were associated with decreased infection rate in the Cx. tarsalis population. The
      resulting monthly models can be used to inform public health interventions by
      improving the predictions of population abundance of Cx. tarsalis and the
      transmission intensity of WNV in the Canadian prairies. Furthermore, these models
      can also be used to examine the potential effects of climate change on the vector
      population abundance and the distribution of WNV. 

PMID- 23880729
TI  - Climate change and West Nile virus in a highly endemic region of North America.
AB  - The Canadian prairie provinces of Manitoba, Saskatchewan, and Alberta have
      reported the highest human incidence of clinical cases of West Nile virus (WNV)
      infection in Canada. The primary vector for WVN in this region is the mosquito
      Culex tarsalis. This study used constructed models and biological thresholds to
      predict the spatial and temporal distribution of Cx. tarsalis and WNV infection
      rate in the prairie provinces under a range of potential future climate and
      habitat conditions. We selected one median and two extreme outcome scenarios to
      represent future climate conditions in the 2020 (2010-2039), 2050 (2040-2069) and
      2080 (2070-2099) time slices. In currently endemic regions, the projected WNV
      infection rate under the median outcome scenario in 2050 raised 17.91 times
      (ranged from 1.29-27.45 times for all scenarios and time slices) comparing to
      current climate conditions. Seasonal availability of Cx. tarsalis infected with
      WNV extended from June to August to include May and September. Moreover, our
      models predicted northward range expansion for Cx. tarsalis (1.06-2.56 times the
      current geographic area) and WNV (1.08-2.34 times the current geographic area).
      These findings predict future public and animal health risk of WNV in the
      Canadian prairie provinces. 

PMID- 23880730
TI  - Care networking: a study of technical mediations in a home telecare service.
AB  - This article examines the processes of technical mediation within familial care
      networks based on a study of home telecare targeted at older people. Supported by
      contributions from the actor-network theory as part of the social psychology of
      science and technology, these processes of technical mediation are analyzed using
      a qualitative approach. The data were gathered through six focus groups and four
      in-depth interviews; the participants in the study included users, relatives and
      formal carers. Thematic analysis techniques encompassing the information were
      used, revealing the effects on the patterns of caring relationships. The results
      show the interplay between presence-absence made possible by the devices; the two
      way direction of care between the older people and the artifacts; and the process
      of sustaining care using the technology. We conclude that care should be seen as
      a socio-technical network where technology plays an active role in sustaining
      family relationships. 

PMID- 23880731
TI  - Dynamics measured by neutron scattering correlates with the organization of
      bioenergetics complexes in natural membranes from hyperthermophile and mesophile
      bacteria.
AB  - Various models on membrane structure and organization of proteins and complexes
      in natural membranes emerged during the last years. However, the lack of
      systematic dynamical studies to complement structural investigations hindered the
      establishment of a more complete picture of these systems. Elastic incoherent
      neutron scattering gives access to the dynamics on a molecular level and was
      applied to natural membranes extracted from the hyperthermophile Aquifex aeolicus
      and the mesophile Wolinella succinogenes bacteria. The results permitted to
      extract a hierarchy of dynamic flexibility and atomic resilience within the
      samples, which correlated with the organization of proteins in bioenergetics
      complexes and the functionality of the membranes. 

PMID- 23880732
TI  - Validation of simulation of calcifications for observer studies in digital
      mammography.
AB  - Studies using simulated calcifications can be performed to measure the effect of
      different imaging factors on calcification detection in digital mammography. The
      simulated calcifications must be inserted into clinical images with realistic
      contrast and sharpness. MoCa is a program which modifies the contrast and
      sharpness of simulated calcification clusters extracted from images of mastectomy
      specimens acquired on a digital specimen cabinet at high magnification for
      insertion into clinical mammography images. This work determines whether the use
      of MoCa results in simulated calcifications with the correct contrast and
      sharpness. Aluminium foils (thickness 0.1-0.4 mm) and 1.60 um thick gold discs
      (diameter 0.13-0.8 mm) on 0.5 mm aluminium were imaged with a range of
      thicknesses of polymethyl methacrylate (PMMA) using an amorphous selenium direct
      digital (DR) system and a powder phosphor computed radiography (CR) system (real
      images). Simulated images of the tests objects were also generated using MoCa.
      The contrast of the aluminium squares and the degradation of the contrast of the
      gold discs as a function of disc diameter were compared in the real and simulated
      images. The average ratios of the simulated-to-real aluminium contrasts over all
      aluminium and PMMA thicknesses were 1.03 +/- 0.04 (two standard errors in the
      mean) and 0.99 +/- 0.03 for the DR and CR systems, respectively. The ratio of the
      simulated-to-real degradations of contrast averaged over all disc diameters and
      PMMA thicknesses were 1.007 +/- 0.008 and 1.002 +/- 0.013 for DR and CR,
      respectively. The use of MoCa was accurate within the experimental errors.

PMID- 23880733
TI  - Seeing the wood through the trees: the current state of higher systematics in the
      Strepsirhini.
AB  - Strepsirhines comprise 10 living or recently extinct families, >=50% of extant
      primate families. Their phylogenetic relationships have been intensively studied,
      but common topologies have only recently emerged; e.g. all recent reconstructions
      link the Lepilemuridae and Cheirogaleidae. The position of the indriids, however,
      remains uncertain, and molecular studies have placed them as the sister to every
      clade except Daubentonia, the preferred sister group of morphologists. The node
      subtending Afro-Asian lorisids has been similarly elusive. We probed these
      phylogenetic inconsistencies using a test data set including 20 strepsirhine taxa
      and 2 outgroups represented by 3,543 mtDNA base pairs, and 43 selected
      morphological characters, subjecting the data to maximum parsimony, maximum
      likelihood and Bayesian inference analyses, and reconstructing topology and node
      ages jointly from the molecular data using relaxed molecular clock analyses. Our
      permutations yielded compatible but not identical evolutionary histories, and
      currently popular techniques seem unable to deal adequately with morphological
      data. We investigated the influence of morphological characters on tree
      topologies, and examined the effect of taxon sampling in two experiments: (1) we
      removed the molecular data only for 5 endangered Malagasy taxa to simulate
      'extinction leaving a fossil record'; (2) we removed both the sequence and
      morphological data for these taxa. Topologies were affected more by the inclusion
      of morphological data only, indicating that palaeontological studies that involve
      inserting a partial morphological data set into a combined data matrix of extant
      species should be interpreted with caution. The gap of approximately 10 million
      years between the daubentoniid divergence and those of the other Malagasy
      families deserves more study. The apparently contemporaneous divergence of
      African and non-daubentoniid Malagasy families 40-30 million years ago may be
      related to regional plume-induced uplift followed by a global period of cooling
      and drying.

PMID- 23880735
TI  - Single-nucleotide polymorphisms in reductase genes are not associated with
      response to daunorubicin-based remission induction.
AB  - BACKGROUND: To improve the quality of care for patients with acute myeloid
      leukemia (AML), biomarkers predictive of response to the standard daunorubicin
      based induction therapy are needed. Genetic variants affecting daunorubicin
      metabolism are attractive candidates for such biomarkers. METHODS: We have
      previously shown that 13 of the naturally occurring nonsynonymous single
      nucleotide polymorphisms (SNP) in the reductase genes affect daunorubicin
      metabolism in vitro. Here, we test these SNPs individually and jointly for
      association with response to one cycle of daunorubicin-based chemotherapy in a
      sample of 189 patients with acute myelogenous leukemia. RESULTS: Of the 13 SNPs
      included in this study, only 5 passed quality control filters. No association was
      found between these 5 SNPs and response to one cycle of daunorubicin-based
      induction therapy in either individual or joint effect tests. CONCLUSIONS:
      Despite their showing in vitro effect on metabolic rate of daunorubicin, the
      nonsynonymous SNPs in the reductase genes on their own are not significant
      contributors to the observed variability in response to daunorubicin therapy and
      thus, as singularities, are not useful biomarkers of this outcome. IMPACT: The
      results of this investigation provide important information for studies on
      personalization of anthracycline-based therapies.

PMID- 23880736
TI  - The effect of heavy metals on microbial community structure of a sulfidogenic
      consortium in anaerobic semi-continuous stirred tank reactors.
AB  - The effect of heavy metals on community structure of a heavy metal tolerant
      sulfidogenic consortium was evaluated by using a combination of denaturing
      gradient gel electrophoresis (DGGE) of 16S rRNA gene and dissimilatory sulfite
      reductase (dsrB) gene fragments, 16S rRNA gene cloning analysis and fluorescence
      in situ hybridization (FISH). For this purpose, four anaerobic semi-continuous
      stirred tank reactors (referred as R1-R4) were run in parallel for 12 weeks at
      heavy metal loading rates of 1.5, 3, 4.5 and 7.5 mg l(-1) d(-1) each of Cu(2+),
      Ni(2+), Zn(2+), and Cr(6+), respectively. The abundance ratio of Desulfovibrio
      vulgaris detected by FISH to total cell counts was consistent with the obtained
      results of cloning and DGGE. This indicated that D. vulgaris was dominant in all
      analyzed samples and played a key role in heavy metal removal in R1, R2, and R3.
      In contrast, after 4 weeks of operation of R4, a distinct biomass loss was
      observed and no positive hybridized cells were detected by specific probes for
      the domain Bacteria, sulfate-reducing bacteria and D. vulgris. High removal
      efficiencies of heavy metals were achieved in R1, R2 and R3 after 12 weeks,
      whereas the precipitation of heavy metals in R4 was significantly decreased after
      4 weeks and almost not observed after 6 weeks of operation. In addition, the
      anaerobic bacteria, such as Pertrimonas sulfuriphila, Clostridium sp.,
      Citrobacter amalonaticus, and Klebsiella sp., identified from DGGE bands and
      clone library were hypothesized as heavy metal resistant bacteria at a loading
      rate of 1.5 mg l(-1) d(-1) of Cu(2+), Ni(2+), Zn(2+), and Cr(6+.) 

PMID- 23880734
TI  - Biomarker-based ovarian carcinoma typing: a histologic investigation in the
      ovarian tumor tissue analysis consortium.
AB  - BACKGROUND: Ovarian carcinoma is composed of five major histologic types, which
      associate with outcome and predict therapeutic response. Our aim was to evaluate
      histologic type assessments across the centers participating in the Ovarian Tumor
      Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction
      model. METHODS: Tissue microarrays (TMA) and clinical data were available for 524
      pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for
      ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three
      histologic type assessments were compared: the original pathologic type, an IHC
      based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review.
      RESULTS: The concordance between TB_COSPv2 type and original type was 73%.
      Applying WT1-assisted core review, the remaining 27% discordant cases subdivided
      into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%).
      The largest discordant subgroup was classified as endometrioid carcinoma by
      original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When
      TB_COSPv2 classification was used, the difference in overall survival of
      endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95%
      confidence interval (CI), 0.37-0.93; P = 0.021], consistent with previous
      reports. In addition, 71 cases with unclear original type could be histologically
      classified by TB_COSPv2. CONCLUSIONS: Research cohorts, particularly those across
      different centers within consortia, show significant variability in original
      histologic type diagnosis. Our IHC-based reclassification produced more
      homogeneous types with respect to outcome than original type. IMPACT: Biomarker
      based classification of ovarian carcinomas is feasible, improves comparability of
      results across research studies, and can reclassify cases which lack reliable
      original pathology.

PMID- 23880737
TI  - Kinetics of enzymatic transesterification and thermal deactivation using
      immobilized Burkholderia lipase as catalyst.
AB  - The most effective way of enzymatic synthesis of biodiesel is through lipase
      catalyzed transesterification, while its performance and economic feasibility
      should still be improved. In this study, lipase produced by an isolated
      Burkholderia sp. was immobilized on microsize Celite materials functionally
      modified with long alkyl groups. The specific activity of the immobilized lipase
      was 1,154 U/g. The methanolysis of olive oil catalyzed by the immobilized lipase
      obeyed Ping Pong Bi Bi model with an estimated V max, K m,TG, K m,M and K i,M
      value of 0.61 mol/(L min), 7.93 mol/L, 1.01 mol/L, and 0.24 mol/L, respectively.
      The activation energy of the enzymatic reaction is estimated as 15.51 kJ/mol. The
      immobilized lipase exhibits high thermal stability with thermal deactivation
      energy of 83 kJ/mol and a long half-life. The enthalpy, Gibb's free energy, and
      entropy of the immobilized lipase were in the range of 80.02-80.35 kJ/mol, 88.35
      90.13 kJ/mol, and -28.22 to -25.11 J/(mol K), respectively. 

PMID- 23880738
TI  - Robotic and laparoscopic partial nephrectomy for T1b tumors.
AB  - PURPOSE OF REVIEW: Laparoscopic and robotic-assisted partial nephrectomy have
      been widely adopted for the management of small renal masses; however, usage in
      T1b (greater than 4 cm) lesions is less established. Herein, we report a review
      on the published series of minimally invasive partial nephrectomies for such
      renal masses. RECENT FINDINGS: Several institutions have described laparoscopic
      and robotic-assisted partial nephrectomy as a safe management option for
      pathologic T1b lesions. The oncologic results are promising, with low positive
      margin rates and few cases of progressive disease. Longer-term renal dysfunction
      does not appear at an increasing rate in this cohort of patients. The safety
      profile appears acceptable; however, there is a slightly increased rate of
      complications in these cohorts of patients. SUMMARY: Laparoscopic and robotic
      assisted partial nephrectomy is a well tolerated and viable option for performing
      minimally invasive surgical extirpation of cT1b renal masses. The oncologic and
      functional results are excellent with acceptable safety profiles. In patients
      with such masses minimally invasive partial nephrectomy should be considered for
      elective and absolute indications. In order to achieve excellent functional and
      oncologic outcomes with minimal perioperative complications an experienced
      surgeon with assistant and assessment of tumor with patient comorbidities are
      important.

PMID- 23880739
TI  - Should histologic variants alter definitive treatment of bladder cancer?
AB  - PURPOSE OF REVIEW: The clinical significance of variant histology is
      controversial and diagnosis is challenging. If variant architecture truly
      identifies high-risk patients, or those with a differential response to therapy,
      than treatment algorithms should be altered. This review outlines the current
      evidence and determines whether histologic variants should indeed alter
      definitive treatment. RECENT FINDINGS: For patients with pure squamous cell,
      adenocarcinoma, or small cell carcinoma, there is clear evidence to alter
      treatment paradigms. In adenocarcinoma or squamous cell carcinoma, there is a
      focus on local control and multimodal therapy with radiation. In small cell
      carcinoma all stages should be treated with primary chemotherapy followed by
      surgical extirpation. For patients with other variants of urothelial
      differentiation (i.e., micropapillary, sarcomatoid, squamous/glandular
      differentiation, etc.), management guidelines are less clear and radical
      cystectomy remains the mainstay of treatment at this time. SUMMARY: The
      management of variant histology is challenging as it not only depends on accurate
      diagnosis and staging, but on assumptions regarding sensitivity to multimodal
      therapy (i.e., chemotherapy, radiation, intravesical agents) based on a handful
      of retrospective case series. This will need to be the focus of future studies
      and collaborative efforts in order to make significant advancements in the field.

PMID- 23880740
TI  - Timing and outcomes for radical cystectomy in nonmuscle invasive bladder cancer.
AB  - PURPOSE OF REVIEW: To provide an overview on the available clinical and
      pathological factors in high-risk nonmuscle invasive bladder cancer (NMIBC)
      patients that help to approximate the risk of progression to muscle invasion and
      identify 'the' patients requiring timely cystectomy. The value of a high-quality
      transurethral tumor resection is pointed out. Outcomes following radical
      cystectomy are compared with a primarily bladder preserving strategy. RECENT
      FINDINGS: Carcinoma in situ within the prostatic urethra of NMIBC patients
      impacts on patient's outcome. Therefore, biopsies taken from the prostatic
      urethra improve the initial tumor staging accuracy. Lamina propria substaging may
      provide more detailed prognostic information. Lympho-vascular invasion within the
      transurethral resection specimen may help to detect patients who benefit from
      timely cystectomy. Recent findings from patients undergoing radical cystectomy
      including super-extended lymphadenectomy for clinically NMIBC confirm the
      substantial rate (25%) of tumor understaging. The fact that almost 10% were found
      to harbor lymph node metastases underlines the necessity to perform a meticulous
      lymphadenectomy in NMIBC patients undergoing radical cystectomy. SUMMARY: High
      quality transurethral bladder tumor resection including underlying muscle fibers
      is of utmost importance. Nevertheless, tumor understaging remains an issue of
      concern and warrants the value of a second transurethral resection in high-risk
      NMIBC patients. There is a persisting lack of rigid therapeutic recommendations
      in patients with high-risk NMIBC. Instead, treatment strategy is based on
      individual risk factors. However, irrespective of initial treatment strategy,
      there is a subgroup of high-risk NMIBC patients with progressive disease, leading
      almost inevitably to death.

PMID- 23880741
TI  - Does minimally invasive surgery for radical cystectomy provide similar long-term
      cancer control as open radical surgery?
AB  - PURPOSE OF REVIEW: Open radical cystectomy (ORC) and pelvic lymph node dissection
      (PLND) is the standard treatment for muscle-invasive and high-risk nonmuscle
      invasive bladder cancer (BCa), but is associated with significant morbidity. In
      the hope of decreasing the complications and improving the surgical tolerance,
      minimally invasive techniques to perform radical cystectomy and PLND have been
      adopted. This review focuses on the present state of the literature regarding the
      oncological efficacy of minimally invasive radical cystectomy (MIRC) and PLND.
      RECENT FINDINGS: Most studies are retrospective, single surgeon or institution,
      and are subjected to significant selection bias. There is scarce data regarding
      intermediate and long term oncological outcomes following MIRC, and most reported
      series contain a lower proportion of patients with locally advanced disease
      compared with ORC series. Positive surgical margin rates are similar between the
      approaches in localized disease, but may be significantly higher in MIRC in
      patients with more advanced tumors. SUMMARY: The current review of the literature
      demonstrates insufficient evidence regarding the long-term oncological outcomes
      of MIRC. There is a need for well controlled, prospective, randomized trials with
      sufficient follow-up to compare MIRC to ORC for the treatment of invasive BCa
      before the oncologic efficacy of these techniques can be adequately compared to
      the standards established by ORC.

PMID- 23880743
TI  - Salvage antibiotic-lock therapy in critically ill pediatric patients: a
      pharmacological review for pediatric intensive care unit nurses.

PMID- 23880742
TI  - Improved identification of wheat gluten proteins through alkylation of cysteine
      residues and peptide-based mass spectrometry.
AB  - The concentration and composition of wheat gluten proteins and the presence,
      concentration and location of cysteine residues therein are important for wheat
      flour quality. However, it is difficult to identify gluten proteins, as they are
      an extremely polymorphic mixture of prolamins. We here present methods for
      cysteine labeling of wheat prolamins with 4-vinylpyridine (4-VP) and
      iodoacetamide (IDAM) which, as compared to label-free analysis, substantially
      improve identification of cysteine-containing peptides in enzymic prolamin
      digests by electrospray ionization--tandem mass spectrometry. Both chymotrypsin
      and thermolysin yielded cysteine-containing peptides from different gluten
      proteins, but more proteins could be identified after chymotryptic digestion. In
      addition, to the best of our knowledge, we were the first to label prolamins with
      isotope coded affinity tags (ICAT), which are commonly used for quantitative
      proteomics. However, more peptides were detected after labeling gluten proteins
      with 4-VP and IDAM than with ICAT.

PMID- 23880745
TI  - What acute care nurse practitioners should understand about reimbursement:
      critical care issues.

PMID- 23880746
TI  - Appropriate staffing for a healthy work environment.

PMID- 23880747
TI  - Collaborative partnerships with patients in pediatric progressive and critical
      care.

PMID- 23880748
TI  - Incentive spirometry in postoperative abdominal/thoracic surgery patients.
AB  - BACKGROUND: Postoperative patients have higher incidences of respiratory
      complications. Patients undergoing abdominal or thoracic surgical procedures are
      at greater risk of having such complications. Incentive spirometry is an
      inhalation-based prophylactic technique that encourages patients to mimic a
      natural deep sigh to periodically increase lung volume. As this technique is the
      prophylactic method of choice for many hospitals, several studies have tested its
      efficacy. METHODS: Five articles, including 4 systematic reviews and 1 clinical
      practice guideline, are analyzed and summarized. Each article was reviewed by a
      multidisciplinary team of health care providers and is discussed herein. A
      clinical recommendation for practice change is provided on the basis of the
      results. SUMMARY: Incentive spirometry is only as effective as cough/deep
      breathing regimens and other means of postoperative pulmonary prophylaxis. No
      single prophylactic technique clearly outperforms all others in preventing
      pulmonary complications. Future research is needed to determine the best method
      to prevent postoperative pulmonary complications.

PMID- 23880749
TI  - Long-term issues after the Fontan procedure.
AB  - The Fontan procedure is used to treat various serious congenital heart defects.
      Although many people who have had the procedure live productively into adulthood,
      as they age, they face several health issues due to the physiology of the Fontan
      circulation. This article reviews the 4 types of Fontan procedures and the
      changes caused by the surgery, including single-ventricle physiology,
      nonpulsatile pulmonary perfusion, systemic venous hypertension, and intracardiac
      scarring, as well as their sequelae. Key nursing assessment items and possible
      treatment strategies are reviewed. Additional topics, including pregnancy in
      patients who have undergone the procedure, infective endocarditis prophylaxis,
      and health-related quality of life, are briefly discussed. Options for Fontan
      failure, including Fontan conversion or transplantation, are presented. Potential
      future solutions are outlined. 

PMID- 23880751
TI  - Calcific uremic arteriolopathy: overview for the nurse.
AB  - Calcific uremic arteriolopathy is a little understood diagnosis of increasing
      prevalence seen predominantly in patients with chronic kidney disease,
      particularly those who are approaching end-stage renal disease, who are
      undergoing renal dialysis, and who have secondary hyperparathyroidism. Calcific
      uremic arteriolopathy affects women more frequently than men, at a ratio of 3:1,
      and the median age at diagnosis is 48 years. A clear understanding of the
      pathogenesis and definitive plans of care are lacking. Nurses should be familiar
      with the clinical picture of calcific uremic arteriolopathy. Early recognition is
      important to develop optimal treatment plans and to limit progression of this
      rare but often fatal disease. Nurses have a pivotal role in maintaining the
      patient's comfort and dignity, while setting realistic goals of care. Calcific
      uremic arteriolopathy remains a rare and complex clinical condition that requires
      a multidisciplinary health care team approach to provide the optimal level of
      care. Nurses have an essential role in the care of patients with the diagnosis of
      calcific uremic arteriolopathy. 

PMID- 23880752
TI  - Endocrine crises in acutely and critically ill patients.

PMID- 23880753
TI  - Multiple endocrine neoplasia: the enigma of MEN.
AB  - Multiple endocrine neoplasia (MEN) is an array of tumors found in various
      endocrine glands throughout the human body. A wide spectrum of clinical
      manifestations accompanies this syndrome. The complexities of the glandular
      function and subtle development of symptoms can cause the diagnosis to be missed,
      and individuals with MEN can be an enigma to the care team. Appropriate
      differential diagnosis and assessment are critical for these individuals to
      receive optimal care. An interprofessional team of health care providers,
      including an endocrinologist and an advanced practice endocrine nurse, must work
      in concert to orchestrate a plan of care across the continuum. Those specialized
      nurses who encounter individuals with MEN in a critical care setting are
      positioned to support the patient, the family, and the care team through this
      maze of multiple endocrinopathies and tumors. 

PMID- 23880754
TI  - Acute diabetes management: adult patients with hyperglycemic crises and
      hypoglycemia.
AB  - In acute diabetes conditions, management of the following 3 potential
      complications is required: diabetic ketoacidosis, hyperosmolar hyperglycemic
      state, and iatrogenic hypoglycemia. The hyperglycemic crises diabetic
      ketoacidosis and hyperosmolar hyperglycemic state are the 2 most serious
      metabolic complications of diabetes. Hypoglycemia, specifically iatrogenic
      hypoglycemia, results from treatments that raise circulating insulin levels and
      thus lower plasma glucose concentrations to an abnormally low level, which
      exposes the patient to potential harm. This article reviews the pathogenesis,
      precipitating or risk factors, diagnosis or identification, and treatment of
      these critical complications of diabetes. In addition, a case study on diabetic
      ketoacidosis is provided. 

PMID- 23880755
TI  - Thyroid gland disorder emergencies: thyroid storm and myxedema coma.
AB  - Although thyroid dysfunction will develop in more than 12% of the US population
      during their lifetimes, true thyroid emergencies are rare. Thyroid storm and
      myxedema coma are endocrine emergencies resulting from thyroid hormone
      dysregulation, usually coupled with an acute illness as a precipitant. Careful
      assessment of risk and rapid action, once danger is identified, are essential for
      limiting morbidity and mortality related to thyroid storm and myxedema coma. This
      article reviews which patients are at risk, explains thyroid storm and myxedema
      coma, and describes pharmacological treatment and supportive cares. 

PMID- 23880756
TI  - Planning for study design and analysis for point-of-care research teams: does
      size matter?

PMID- 23880757
TI  - Sex variation in the electrocardiogram.

PMID- 23880758
TI  - Transient reduction of 5-methylcytosine and 5-hydroxymethylcytosine is associated
      with active DNA demethylation during regeneration of zebrafish fin.
AB  - Although dedifferentiation, transformation of differentiated cells into
      progenitor cells, is a critical step in the regeneration of amphibians and fish,
      the molecular mechanisms underlying this process, including epigenetic changes,
      remain unclear. Dot blot assays and immunohistochemical analyses revealed that,
      during regeneration of zebrafish fin, the levels of 5-methylcytosine (5mC) and 5
      hydroxymethylcytosine (5hmC) are transiently reduced in blastema cells and cells
      adjacent to the amputation plane at 30 h post-amputation (hpa), and the level of
      5mC, but not 5hmC, is almost restored by 72 hpa. We observed that the
      dedifferentiated cells showed reduced levels of 5mC and 5hmC independent of cell
      proliferation by 24 hpa. Furthermore, expressions of the proposed demethylation-
      and DNA repair-related genes were detected during fin regeneration. Taken
      together, our findings illustrate that the transient reduction of 5mC and 5hmC in
      dedifferentiated cells is associated with active demethylation during
      regeneration of zebrafish fin.

PMID- 23880759
TI  - Relief of autoinhibition enhances Vta1 activation of Vps4 via the Vps4
      stimulatory element.
AB  - The endosomal sorting complexes required for transport (ESCRTs) impact multiple
      cellular processes including multivesicular body sorting, abscission, and viral
      budding. The AAA-ATPase Vps4 is required for ESCRT function, and its full
      activity is dependent upon the co-factor Vta1. The Vta1 carboxyl-terminal Vta1
      SBP1 Lip5 (VSL) domain stimulates Vps4 function by facilitating oligomerization
      of Vps4 into its active state. Here we report the identification of the Vps4
      stimulatory element (VSE) within Vta1 that is required for additional stimulation
      of Vps4 activity in vitro and in vivo. VSE activity is autoinhibited in a manner
      dependent upon the unstructured linker region joining the amino-terminal
      microtubule interacting and trafficking domains and the carboxyl-terminal VSL
      domain. The VSE is also required for Vta1-mediated Vps4 stimulation by ESCRT-III
      subunits Vps60 and Did2. These results suggest that ESCRT-III binding to the Vta1
      microtubule interacting and trafficking domains relieves linker region
      autoinhibition of the VSE to produce maximal activation of Vps4 during ESCRT
      function. 

PMID- 23880760
TI  - Regulation of hypoxia-inducible factor 1alpha (HIF-1alpha) by lysophosphatidic
      acid is dependent on interplay between p53 and Kruppel-like factor 5.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) and p53 are pivotal regulators of
      tumor growth. Lysophosphatidic acid (LPA) is a lipid mediator that functions as a
      mitogen by acting through LPA receptors. We have shown previously that LPA
      stimulates HIF-1alpha expression in colon cancer cells. To determine the
      mechanism of HIF-1alpha induction by LPA, we compared the effect of LPA on HIF
      1alpha in several colon cancer cell lines. LPA transcriptionally induced HIF
      1alpha in colon cancer cells. HIF-1alpha induction was observed in cells
      expressing WT p53, where LPA decreased p53 expression. However, LPA failed to
      induce HIF-1alpha when the p53 gene was mutated. A decrease in p53 expression was
      dependent on induction of p53-specific E3 ubiquitin ligase Mdm2 by LPA. Kruppel
      like factor 5 (KLF5) is an effector of LPA-induced proliferation of colon cancer
      cells. Because HIF-1alpha was necessary for LPA-induced growth of colon cancer
      cells, we determined the relationship between KLF5 and HIF-1alpha by a loss-of
      function approach. Silencing of KLF5 inhibited LPA-induced HIF-1alpha induction,
      suggesting that KLF5 is an upstream regulator of HIF-1alpha. KLF5 and p53 binding
      to the Hif1alpha promoter was assessed by ChIP assay. LPA increased the occupancy
      of the Hif1alpha promoter by KLF5, while decreasing p53 binding. Transfection of
      HCT116 cells with KLF5 or p53 attenuated the binding of the other transcription
      factor. These results identify KLF5 as a transactivator of HIF-1alpha and show
      that LPA regulates HIF-1alpha by dynamically modulating its interaction with KLF5
      and p53. 

PMID- 23880761
TI  - Progesterone receptor A stability is mediated by glycogen synthase kinase-3beta
      in the Brca1-deficient mammary gland.
AB  - Germ line mutations of the BRCA1 gene increase the risk of breast and ovarian
      cancer, but the basis of this tissue-specific tumor predisposition is not fully
      understood. Previously, we reported that the progesterone receptors are
      stabilized in Brca1-deficient mammary epithelial cells, and treating with anti
      progesterone delays mammary tumorigenesis in Brca1/p53 conditional knock-out
      mice, suggesting that the progesterone has a critical role in breast
      carcinogenesis. To further explore how the stability of progesterone receptor is
      modulated, here, we have found that glycogen synthase kinase (GSK)-3beta
      phosphorylation of progesterone receptor-A (PR-A) facilitates its ubiquitination.
      GSK-3beta-mediated phosphorylation of serine 390 in PR-A regulates its subsequent
      ubiquitination and protein stability. Expression of PR-A(S390A) mutant in the
      human breast epithelial cells, MCF-10A, results in enhanced proliferation and
      formation of aberrant acini structure in the three-dimensional culture.
      Consistently, reduction of phosphorylation of serine 390 of PR-A and GSK-3beta
      activity is observed in the Brca1-deficient mammary gland. Taken together, these
      results provide important aspects of tissue specificity of BRCA1-mediated
      suppression of breast carcinogenesis. 

PMID- 23880762
TI  - Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor
      initiated signal transduction.
AB  - T cell receptor (TCR)-initiated signal transduction is reported to increase
      production of intracellular reactive oxygen species, such as superoxide (O2(-))
      and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate
      signal transduction by inactivating protein phosphatases, the mechanism and the
      subcellular localization of intracellular H2O2 as a second messenger of the TCR
      are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the
      dismutation of highly reactive O2(-) into H2O2 and thus acts as an intracellular
      generator of H2O2. As charged O2(-) is unable to diffuse through intracellular
      membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and
      mitochondria (Mn-SOD), where they locally scavenge O2(-) leading to production of
      H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell
      lines increases intracellular production of H2O2 but does not alter the levels of
      intracellular H2O2 scavenging enzymes such as catalase, membrane-bound
      peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn
      SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal
      transduction molecules Lck, LAT, ZAP70, PLCgamma1, and SLP76 within 1 min of TCR
      cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK
      signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no
      effect on any of these TCR-mediated signaling molecules. As mitochondria
      translocate to the immunological synapse during TCR activation, we hypothesize
      this translocation provides the effective concentration of H2O2 required to
      selectively modulate downstream signal transduction pathways.

PMID- 23880763
TI  - Naive-like conversion overcomes the limited differentiation capacity of induced
      pluripotent stem cells.
AB  - Although induced pluripotent stem (iPS) cells are indistinguishable from ES cells
      in their expression of pluripotent markers, their differentiation into targeted
      cells is often limited. Here, we examined whether the limited capacity of iPS
      cells to differentiate into neural lineage cells could be mitigated by improving
      their base-line level of pluripotency, i.e. by converting them into the so-called
      "naive" state. In this study, we used rabbit iPS and ES cells because of the easy
      availability of both cell types and their typical primed state characters.
      Repeated passages of the iPS cells permitted their differentiation into early
      neural cell types (neural stem cells, neurons, and glial astrocytes) with
      efficiencies similar to ES cells. However, unlike ES cells, their ability to
      differentiate later into neural cells (oligodendrocytes) was severely
      compromised. In contrast, after these iPS cells had been converted to a naive
      like state, they readily differentiated into mature oligodendrocytes developing
      characteristic ramified branches, which could not be attained even with ES cells.
      These results suggest that the naive-like conversion of iPS cells might endow
      them with a higher differentiation capacity. 

PMID- 23880764
TI  - Role of pancreatic cancer-derived exosomes in salivary biomarker development.
AB  - Recent studies have demonstrated that discriminatory salivary biomarkers can be
      readily detected upon the development of systemic diseases such as pancreatic
      cancer, breast cancer, lung cancer, and ovarian cancer. However, the utility of
      salivary biomarkers for the detection of systemic diseases has been undermined
      due to the absence of the biological and mechanistic rationale as to why distal
      diseases from the oral cavity would lead to the development of discriminatory
      biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor
      derived exosomes are mechanistically involved in the development of pancreatic
      cancer-discriminatory salivary transcriptomic biomarkers. We first developed a
      pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by
      implanting the mouse pancreatic cancer cell line Panc02 into the pancreas of the
      syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the
      development of discriminatory salivary biomarkers was then tested by engineering
      a Panc02 cell line that is suppressed for exosome biogenesis, implanting into the
      C56BL/6 mouse, and examining whether the discriminatory salivary biomarker
      profile was ablated or disrupted. Suppression of exosome biogenesis results in
      the ablation of discriminatory salivary biomarker development. This study
      supports that tumor-derived exosomes provide a mechanism in the development of
      discriminatory biomarkers in saliva and distal systemic diseases. 

PMID- 23880765
TI  - CD73 protein as a source of extracellular precursors for sustained NAD+
      biosynthesis in FK866-treated tumor cells.
AB  - NAD(+) is mainly synthesized in human cells via the "salvage" pathways starting
      from nicotinamide, nicotinic acid, or nicotinamide riboside (NR). The inhibition
      with FK866 of the enzyme nicotinamide phosphoribosyltransferase (NAMPT),
      catalyzing the first reaction in the "salvage" pathway from nicotinamide, showed
      potent antitumor activity in several preclinical models of solid and hematologic
      cancers. In the clinical studies performed with FK866, however, no tumor
      remission was observed. Here we demonstrate that low micromolar concentrations of
      extracellular NAD(+) or NAD(+) precursors, nicotinamide mononucleotide (NMN) and
      NR, can reverse the FK866-induced cell death, this representing a plausible
      explanation for the failure of NAMPT inhibition as an anti-cancer therapy. NMN is
      a substrate of both ectoenzymes CD38 and CD73, with generation of NAM and NR,
      respectively. In this study, we investigated the roles of CD38 and CD73 in
      providing ectocellular NAD(+) precursors for NAD(+) biosynthesis and in
      modulating cell susceptibility to FK866. By specifically silencing or
      overexpressing CD38 and CD73, we demonstrated that endogenous CD73 enables,
      whereas CD38 impairs, the conversion of extracellular NMN to NR as a precursor
      for intracellular NAD(+) biosynthesis in human cells. Moreover, cell viability in
      FK866-treated cells supplemented with extracellular NMN was strongly reduced in
      tumor cells, upon pharmacological inhibition or specific down-regulation of CD73.
      Thus, our study suggests that genetic or pharmacologic interventions interfering
      with CD73 activity may prove useful to increase cancer cell sensitivity to NAMPT
      inhibitors. 

PMID- 23880766
TI  - Basal autophagy is required for the efficient catabolism of
      sialyloligosaccharides.
AB  - Macroautophagy is an essential, homeostatic process involving degradation of a
      cell's own components; it plays a role in catabolizing cellular components, such
      as protein or lipids, and damaged or excess organelles. Here, we show that in
      Atg5(-/-) cells, sialyloligosaccharides specifically accumulated in the cytosol.
      Accumulation of these glycans was observed under non-starved conditions,
      suggesting that non-induced, basal autophagy is essential for their catabolism.
      Interestingly, once accumulated in the cytosol, sialylglycans cannot be
      efficiently catabolized by resumption of the autophagic process, suggesting that
      functional autophagy is important for preventing sialyloligosaccharides from
      accumulating in the cytosol. Moreover, knockdown of sialin, a lysosomal
      transporter of sialic acids, resulted in a significant reduction of
      sialyloligosaccharides, implying that autophagy affects the substrate specificity
      of this transporter. This study thus provides a surprising link between basal
      autophagy and catabolism of N-linked glycans. 

PMID- 23880767
TI  - beta-Glucosidase 2 (GBA2) activity and imino sugar pharmacology.
AB  - beta-Glucosidase 2 (GBA2) is an enzyme that cleaves the membrane lipid
      glucosylceramide into glucose and ceramide. The GBA2 gene is mutated in genetic
      neurological diseases (hereditary spastic paraplegia and cerebellar ataxia).
      Pharmacologically, GBA2 is reversibly inhibited by alkylated imino sugars that
      are in clinical use or are being developed for this purpose. We have addressed
      the ambiguity surrounding one of the defining characteristics of GBA2, which is
      its sensitivity to inhibition by conduritol B epoxide (CBE). We found that CBE
      inhibited GBA2, in vitro and in live cells, in a time-dependent fashion, which is
      typical for mechanism-based enzyme inactivators. Compared with the well
      characterized impact of CBE on the lysosomal glucosylceramide-degrading enzyme
      (glucocerebrosidase, GBA), CBE inactivated GBA2 less efficiently, due to a lower
      affinity for this enzyme (higher KI) and a lower rate of enzyme inactivation
      (k(inact)). In contrast to CBE, N-butyldeoxygalactonojirimycin exclusively
      inhibited GBA2. Accordingly, we propose to redefine GBA2 activity as the beta
      glucosidase that is sensitive to inhibition by N-butyldeoxygalactonojirimycin.
      Revised as such, GBA2 activity 1) was optimal at pH 5.5-6.0; 2) accounted for a
      much higher proportion of detergent-independent membrane-associated beta
      glucosidase activity; 3) was more variable among mouse tissues and neuroblastoma
      and monocyte cell lines; and 4) was more sensitive to inhibition by N
      butyldeoxynojirimycin (miglustat, Zavesca(r)), in comparison with earlier
      studies. Our evaluation of GBA2 makes it possible to assess its activity more
      accurately, which will be helpful in analyzing its physiological roles and
      involvement in disease and in the pharmacological profiling of monosaccharide
      mimetics.

PMID- 23880768
TI  - GTP is the primary activator of the anti-HIV restriction factor SAMHD1.
AB  - SAMHD1 (SAM domain- and HD domain-containing protein 1) is a dGTP-dependent dNTP
      triphosphohydrolase that converts dNTPs into deoxyribonucleosides and
      triphosphates. Therefore, SAMHD1 expression, particularly in non-dividing cells,
      can restrict retroviral infections such as HIV and simian immunodeficiency virus
      by limiting cellular dNTPs, which are essential for reverse transcription. It has
      previously been established that dGTP acts as both an activator and a substrate
      of this enzyme, suggesting that phosphohydrolase activity of SAMHD1 is regulated
      by dGTP availability in the cell. However, we now demonstrate biochemically that
      the NTP GTP is equally capable of activating SAMHD1, but GTP is not hydrolyzed by
      the enzyme. Activation of SAMHD1 phosphohydrolase activity was tested under
      physiological concentrations of dGTP or GTP found in either dividing or non
      dividing cells. Because GTP is 1000-fold more abundant than dGTP in cells, GTP
      was able to activate the enzyme to a greater extent than dGTP, suggesting that
      GTP is the primary activator of SAMHD1. Finally, we show that SAMHD1 has the
      ability to hydrolyze base-modified nucleotides, indicating that the active site
      of SAMHD1 is not restrictive to such modifications, and is capable of regulating
      the levels of non-canonical dNTPs such as dUTP. This study provides further
      insights into the regulation of SAMHD1 with regard to allosteric activation and
      active site specificity. 

PMID- 23880769
TI  - Galactose 6-O-sulfotransferases are not required for the generation of Siglec-F
      ligands in leukocytes or lung tissue.
AB  - Eosinophil accumulation is a characteristic feature of the immune response to
      parasitic worms and allergens. The cell surface carbohydrate-binding receptor
      Siglec-F is highly expressed on eosinophils and negatively regulates their
      accumulation during inflammation. Although endogenous ligands for Siglec-F have
      yet to be biochemically defined, binding studies using glycan arrays have
      implicated galactose 6-O-sulfate (Gal6S) as a partial recognition determinant for
      this receptor. Only two sulfotransferases are known to generate Gal6S, namely
      keratan sulfate galactose 6-O-sulfotransferase (KSGal6ST) and chondroitin 6-O
      sulfotransferase 1 (C6ST-1). Here we use mice deficient in both KSGal6ST and C6ST
      1 to determine whether these sulfotransferases are required for the generation of
      endogenous Siglec-F ligands. First, we characterize ligand expression on
      leukocyte populations and find that ligands are predominantly expressed on cell
      types also expressing Siglec-F, namely eosinophils, neutrophils, and alveolar
      macrophages. We also detect Siglec-F ligand activity in bronchoalveolar lavage
      fluid fractions containing polymeric secreted mucins, including MUC5B. Consistent
      with these observations, ligands in the lung increase dramatically during
      infection with the parasitic nematode, Nippostrongylus brasiliensis, which is
      known to induce eosinophil accumulation and mucus production. Surprisingly, Gal6S
      is undetectable in sialylated glycans from eosinophils and BAL fluid analyzed by
      mass spectrometry. Furthermore, none of the ligands we describe are diminished in
      mice lacking KSGal6ST and C6ST-1, indicating that neither of the known galactose
      6-O-sulfotransferases is required for ligand synthesis. These results establish
      that ligands for Siglec-F are present on several cell types that are relevant
      during allergic lung inflammation and argue against the widely held view that
      Gal6S is critical for glycan recognition by this receptor. 

PMID- 23880770
TI  - Ubiquitin interacts with the Tollip C2 and CUE domains and inhibits binding of
      Tollip to phosphoinositides.
AB  - A large number of cellular signaling processes are directed through
      internalization, via endocytosis, of polyubiquitinated cargo proteins. Tollip is
      an adaptor protein that facilitates endosomal cargo sorting for lysosomal
      degradation. Tollip preferentially binds phosphatidylinositol 3-phosphate
      (PtdIns(3)P) via its C2 domain, an association that may be required for endosomal
      membrane targeting. Here, we show that Tollip binds ubiquitin through its C2 and
      CUE domains and that its association with the C2 domain inhibits PtdIns(3)P
      binding. NMR analysis demonstrates that the C2 and CUE domains bind to
      overlapping sites on ubiquitin, suggesting that two ubiquitin molecules associate
      with Tollip simultaneously. Hydrodynamic studies reveal that ubiquitin forms
      heterodimers with the CUE domain, indicating that the association disrupts the
      dimeric state of the CUE domain. We propose that, in the absence of
      polyubiquitinated cargo, the dual binding of ubiquitin partitions Tollip into
      membrane-bound and membrane-free states, a function that contributes to the
      engagement of Tollip in both membrane trafficking and cytosolic pathways. 

PMID- 23880773
TI  - Flexible, linear, tetranuclear palladium complexes supported by tetraphosphine
      ligands with electron-withdrawing groups.
AB  - A linearly ordered tetraphosphine containing electron-withdrawing substituent
      groups on the outer phosphorus atoms, meso-bis[{di(3,5
      difluorophenyl)phosphinomethyl}phenylphosphino]methane (dpmppmF2), was prepared
      and reacted with [Pd2(RNC)6](PF6)2 and Pd(dba)2 to afford tetranuclear palladium
      complexes, [Pd4(MU-dpmppmF2)2(RNC)3](PF6)2 (R = 2,6-xylyl (Xyl) (1), 2,4,6
      mesityl (2), 2,6-diisopropylphenyl (3) and tert-butyl (4)), which involve an
      asymmetric {(RNC)Pd4(CNR)2}(2+) core supported by two dpmppmF2 ligands in anti
      arrangement. Each terminal of the Pd4 chain was capped by terminal isocyanide and
      a semi-bridging RNC is introduced into one terminal Pd site. Mechanistic
      investigation suggested that the dipalladium(I) complex, [Pd2(MU
      dpmppmF2)2(RNC)2](PF6)2 (R = Xyl (6)), was a key intermediate to trap Pd(0)
      species by the uncoordinated outer phosphine pendants with electron-withdrawing
      groups. Variable-temperature UV-vis and (31)P{(1)H}, (1)H NMR spectroscopic
      studies demonstrated that the tetrapalladium complexes are quite fluxional in the
      solution state at high temperature (>20  degrees C) relating to a symmetric
      structure of [Pd4(MU-dpmppmF2)2(RNC)2](PF6)2, and the asymmetric solid state
      structures are retained even in the solution at low temperature (<-60  degrees
      C). Theoretical calculations with DFT methods on the asymmetric (R = Xyl (1)) and
      symmetric (R = Xyl (1')) structures suggested that contribution of Pd(0)->Pd(I)
      Pd(0)-Pd(I) with 60 cluster valence electrons (CVEs) would be dominant in 1,
      while the symmetric structure of 1' can be recognized as Pd(I)-Pd(0)-Pd(0)-Pd(I)
      with 58 CVEs. The new tetraphosphine dpmppmF2 was proven very effective in
      organizing dynamically flexible tetrapalladium chains.

PMID- 23880771
TI  - Development of a human IgG4 bispecific antibody for dual targeting of interleukin
      4 (IL-4) and interleukin-13 (IL-13) cytokines.
AB  - Human bispecific antibodies have great potential for the treatment of human
      diseases. Although human IgG1 bispecific antibodies have been generated, few
      attempts have been reported in the scientific literature that extend bispecific
      antibodies to other human antibody isotypes. In this paper, we report our work
      expanding the knobs-into-holes bispecific antibody technology to the human IgG4
      isotype. We apply this approach to generate a bispecific antibody that targets IL
      4 and IL-13, two cytokines that play roles in type 2 inflammation. We show that
      IgG4 bispecific antibodies can be generated in large quantities with equivalent
      efficiency and quality and have comparable pharmacokinetic properties and lung
      partitioning, compared with the IgG1 isotype. This work broadens the range of
      published therapeutic bispecific antibodies with natural surface architecture and
      provides additional options for the generation of bispecific antibodies with
      differing effector functions through the use of different antibody isotypes. 

PMID- 23880772
TI  - Deletion of selenoprotein M leads to obesity without cognitive deficits.
AB  - Selenium is an essential trace element that is co-translationally incorporated
      into selenoproteins in the form of the 21st amino acid, selenocysteine. This
      class of proteins largely functions in oxidation-reduction reactions and is
      critically involved in maintaining proper redox balance essential to health.
      Selenoprotein M (SelM) is a thioredoxin-like endoplasmic reticulum-resident
      protein that is highly expressed in the brain and possesses neuroprotective
      properties. In this study, we first assessed the regional pattern of SelM
      expression in the mouse brain to provide insights into the potential functional
      implications of this protein in physiology and behavior. Next, we generated
      transgenic mice with a targeted deletion of the SelM gene and subjected them to a
      battery of neurobehavioral tests to evaluate motor coordination, locomotion, and
      cognitive function in comparison with wild-type controls. Finally, these mice
      were tested for several measures of metabolic function and body composition. Our
      results show that SelM knock-out (KO) mice display no deficits in measures of
      motor coordination and cognitive function but exhibit increased weight gain,
      elevated white adipose tissue deposition, and diminished hypothalamic leptin
      sensitivity. These findings suggest that SelM plays an important role in the
      regulation of body weight and energy metabolism. 

PMID- 23880774
TI  - Public reporting of health care-associated infection rates: are consumers aware
      and engaged?

PMID- 23880775
TI  - A simulation-based training program improves emergency department staff
      communication.
AB  - The objectives of this study were to evaluate the effectiveness of Project
      CLEAR!, a novel simulation-based training program designed to instill Crew
      Resource Management (CRM) as the communication standard and to create a service
      focused environment in the emergency department (ED) by standardizing the patient
      encounter. A survey-based study compared physicians' and nurses' perceptions of
      the quality of communication before and after the training program. Surveys were
      developed to measure ED staff perceptions of the quality of communication between
      staff members and with patients. Pretraining and posttraining survey results were
      compared. After the training program, survey scores improved significantly on
      questions that asked participants to rate the overall communication between staff
      members and between staff and patients. A simulation-based training program
      focusing on CRM and standardizing the patient encounter improves communication in
      the ED, both between staff members and between staff members and patients. 

PMID- 23880776
TI  - Acute care quality improves while barriers to access remain: AHRQ's 2012
      healthcare quality and disparities reports.

PMID- 23880777
TI  - Standardizing central line safety: lessons learned for physician leaders.
AB  - A comprehensive central venous catheter (CVC) safety program reduces mechanical
      and infectious complications and requires an integrated multidisciplinary effort.
      A multistate health care system implemented a discovery and diffusion project
      addressing CVC insertion, maintenance, and removal. Process and outcome measures
      were collected before and after the intervention. The project was completed in 12
      months. It was associated with statistically significant improvement in 6 process
      measures and reduction in the rate of ICU central line-associated bloodstream
      infection (from 1.16 to 0.80 infections/1000 catheter days; incidence rate ratio
      = 0.69; 95% confidence interval = 0.51, 0.93). A comprehensive CVC
      standardization project increased compliance with several established best
      practices, was associated with improved outcomes, produced a refined definition
      of discovery and diffusion project components, and identified several discrete
      leadership principles that can be applied to future clinical improvement
      initiatives. 

PMID- 23880778
TI  - A fine tuning of metallaborane to bridged-boryl complex, [(Cp*Ru)2(MU-H)(MU
      CO)(MU-Bcat)] (cat = 1,2-O2C6H4; Cp* = eta5-C5Me5).
AB  - Room temperature photolysis of [(Cp*RuCO)2BH4(Bcat)], 3, generated from the
      reaction of arachno-[(Cp*RuCO)2B2H6], 1, with HBcat (cat = 1,2-O2C6H4), yielded a
      rare homodinuclear bridged-boryl complex, [(Cp*Ru)2(MU-H)(MU-CO)(MU-Bcat)], 4,
      confirmed by X-ray diffraction. 

PMID- 23880779
TI  - Impact of the volume change on the ageing effects in Cu-Al-Ni martensite:
      experiment and theory.
AB  - The time evolution of the physical properties of martensite during martensite
      ageing is traditionally explained by the symmetry-conforming short-range order
      (SC-SRO) principle, which requires the spatial configuration of crystal defects
      to follow the symmetry change of the host lattice. In the present study, we show
      that the volume change of the host lattice also contributes to the ageing effects
      in Cu-Al-Ni shape memory alloy besides the symmetry change. To substantiate this
      statement the gradual increase of the storage modulus with time at constant
      temperature was measured by dynamic mechanical analysis (DMA) and the
      experimental results were quantitatively described in the framework of the
      symmetry-conforming Landau theory of martensitic transformations in a crystal
      with defects. The comparison of experimental and theoretical results confirmed
      that the time dependence of the storage modulus is caused by two different
      physical mechanisms. Evaluations showing that the first mechanism is driven by
      the spontaneous symmetry change and the second mechanism is caused by the volume
      change after the martensitic transformation was carried out. 

PMID- 23880780
TI  - Spectral and redox properties of the GFP synthetic chromophores as a function of
      pH in buffered media.
AB  - The effect of pH on the spectral and redox properties of model GFP synthetic
      chromophores (Cros) in a universal buffer system was investigated. The Cro
      hydroxy-derivatives demonstrated a Nernst-type electrochemical dependence of the
      anodic potential within the pH 2-8 range. Analogous studies on various
      fluorescent proteins were unsuccessful. 

PMID- 23880781
TI  - Efficacy and side effects of dacarbazine in comparison with temozolomide in the
      treatment of malignant melanoma: a meta-analysis consisting of 1314 patients.
AB  - The widespread prevalence of melanoma, one of the most malignant forms of skin
      cancer, is increasing rapidly. Two chemotherapeutic regimens are commonly used
      for the palliative treatment of malignant melanoma: intravenous administration of
      single-agent dacarbazine or oral administration of temozolomide. The aim of this
      study was to compare the effectiveness and side effects of dacarbazine with those
      of temozolomide through a meta-analysis. A thorough literature bibliography
      search was conducted up to 2012 to gather and review all randomized clinical
      trials comparing the use of dacarbazine with that of temozolomide in the
      treatment of malignant melanoma. Three head-to-head randomized clinical trials
      comprising 1314 patients met the criteria and were included. Comparison of
      temozolomide with dacarbazine yielded a nonsignificant relative risk (RR) of 0.83
      [95% confidence interval (CI) = 0.26-2.64, P = 0.76] for complete response, a
      nonsignificant RR of 1.05 (95% CI = 0.85-1.3, P = 0.65) for stable disease, and a
      nonsignificant RR of 2.64 (95% CI = 0.97-1.36, P = 0.11) for disease control
      rate. The RR for nonhematologic side effects and hematologic side effects, such
      as anemia, neutropenia, and thrombocytopenia, of temozolomide compared with
      dacarbazine in patients with malignant melanoma was nonsignificant in all cases,
      but the RR for lymphopenia of temozolomide compared with dacarbazine was 3.79
      (95% CI = 1.38-10.39, P = 0.01), which was significant. Although it is easier to
      administer oral medication, according to the results, there is no significant
      difference in the efficacy and side effects of these two drugs. Owing to the
      higher cost of treatment with temozolomide and the increased prevalence of
      lymphopenia on using temozolomide, use of dacarbazine as the first choice
      treatment for malignant melanoma is suggested.

PMID- 23880782
TI  - Secondary organic aerosols over oceans via oxidation of isoprene and monoterpenes
      from Arctic to Antarctic.
AB  - Isoprene and monoterpenes are important precursors of secondary organic aerosols
      (SOA) in continents. However, their contributions to aerosols over oceans are
      still inconclusive. Here we analyzed SOA tracers from isoprene and monoterpenes
      in aerosol samples collected over oceans during the Chinese Arctic and Antarctic
      Research Expeditions. Combined with literature reports elsewhere, we found that
      the dominant tracers are the oxidation products of isoprene. The concentrations
      of tracers varied considerably. The mean average values were approximately one
      order of magnitude higher in the Northern Hemisphere than in the Southern
      Hemisphere. High values were generally observed in coastal regions. This
      phenomenon was ascribed to the outflow influence from continental sources. High
      levels of isoprene could emit from oceans and consequently have a significant
      impact on marine SOA as inferred from isoprene SOA during phytoplankton blooms,
      which may abruptly increase up to 95 ng/m3 in the boundary layer over remote
      oceans.

PMID- 23880784
TI  - A novel hybrid CFHR1/CFH gene causes atypical hemolytic uremic syndrome.
AB  - BACKGROUND: Mutations in complement factor H (CFH) are associated with complement
      dysregulation and the development of an aggressive form of atypical hemolytic
      uremic syndrome (aHUS) that progresses to end-stage renal disease (ESRD) and in
      most patients has a high rate of recurrence following transplantation. Sequence
      analysis of CFH and its downstream complement factor H-related genes (CFHR1-5)
      reveals several macrohomologous blocks caused by large genomic duplications. This
      high degree of sequence identity renders this area susceptible to nonallelic
      homologous recombination (NAHR) events, resulting in large-scale deletions,
      duplications, and the generation of hybrid CFH genes. CASE-DIAGNOSIS: Here, we
      report the finding of a novel CFHR1/CFH hybrid gene created by a de novo NAHR
      event in a 14-year-old girl with aHUS. The resulting fusion protein contains the
      first three short consensus repeats (SCRs) of CFHR1 and the terminal two SCRs of
      CFH. CONCLUSIONS: This finding demonstrates a novel pathogenic mechanism for the
      development of aHUS. Additionally, since standard Sanger sequencing is unable to
      detect such rearrangements, all aHUS patients should receive comprehensive
      genetic screening that includes analysis of copy number variation in order to
      identify patients with poor clinical prognoses.

PMID- 23880785
TI  - Uromodulin: old friend with new roles in health and disease.
AB  - The most abundant urinary protein, Tamm-Horsfall protein, later renamed
      uromodulin, is expressed exclusively by the thick ascending limb cells of the
      kidney and released into urine from the apical cell membrane. Uromodulin is
      believed to protect against urinary tract infections and stones, but its other
      physiologic functions have remained obscure until recently. Renewed interest in
      uromodulin has been brought about by the identification of uromodulin mutations
      as causes of a discrete group of diseases that are distinct from
      nephronophthisis. The three overlapping clinical uromodulin-associated kidney
      diseases (UAKD) are medullary cystic disease type 2, familial juvenile
      hyperuricemic nephropathy and glomerulocystic kidney disease. Previously thought
      of as "adult diseases", it is now recognized that they may also present in
      childhood and even in infancy. Common characteristics of all three diseases are
      autosomal dominant inheritance, unremarkable urine sediment and slow progression
      to end-stage renal disease (ESRD). They are frequently associated with
      hyperuricemia and gout. These diseases appear to result from failure of the
      mutant uromodulin to be incorporated into the apical cilium, thereby placing UAKD
      in the category of "ciliopathies". In addition to causing specific UAKD, certain
      uromodulin gene polymorphisms have been linked to ESRD in general, suggesting
      that uromodulin plays a modulatory role in kidney disease progression. 

PMID- 23880786
TI  - Concomitant ligamentous and meniscal knee injuries in femoral shaft fracture.
AB  - BACKGROUND: Concomitant knee injury is a common finding in femoral fractures but
      can be easily missed during early management of the initial trauma. Degrees of
      damage to the articular structures vary considerably; from only a mild effusion
      to complete ligamentous and meniscal tears. Since previous reports were mostly
      from developed societies, this study was designed to look into characteristics of
      associated knee injury in a sample from Iran, to represent a developing country
      perspective. MATERIALS AND METHODS: Consecutive patients admitted to an
      orthopedic ward of Baqiyatallah hospital (Tehran, Iran) with diagnosis of femoral
      fracture were enrolled in this study between October 2008 and September 2009. In
      patients who met the inclusion criteria of the study, arthroscopic or open
      surgical examination of the knee, ADT, Lachman test, varus and valgus stress
      tests under anesthesia were carried out to determine the incidence of knee
      injury. RESULTS: Forty patients with ipsilateral and two patients with bilateral
      femoral fractures were studied. Arthroscopy revealed medial meniscus injury in 12
      (27%) knees. Three (7%) lateral meniscus injuries, 18 (40.9%) ACL injuries and 2
      (4.5%) PCL injuries were also found. In varus and valgus stress tests, 15 (34%)
      MCL and 4 (9%) LCL laxities were noticed. The Lachman test was positive in 3
      (6%), and ADT was positive in 2 (4.5%) patients. CONCLUSIONS: Based on our
      observations, concomitant ligamentous and meniscal knee injury is a common
      finding in femoral shaft fractures and rates of these injuries are generally in
      concert with reports from developed nations.

PMID- 23880787
TI  - Characteristics of differentiated CD8(+) and CD4 (+) T cells present in the human
      brain.
AB  - Immune surveillance of the central nervous system (CNS) by T cells is important
      to keep CNS-trophic viruses in a latent state, yet our knowledge of the
      characteristics of CNS-populating T cells is incomplete. We performed a
      comprehensive, multi-color flow-cytometric analysis of isolated T cells from
      paired corpus callosum (CC) and peripheral blood (PB) samples of 20 brain donors.
      Compared to PB, CC T cells, which were mostly located in the perivascular space
      and sporadically in the parenchyma, were enriched for cells expressing CD8. Both
      CD4(+) and CD8(+) T cells in the CC had a late-differentiated phenotype, as
      indicated by lack of expression of CD27 and CD28. The CC contained high numbers
      of T cells expressing chemokine receptor CX3CR1 and CXCR3 that allow for homing
      to inflamed endothelium and tissue, but hardly cells expressing the lymph node
      homing receptor CCR7. Despite the late-differentiated phenotype, CC T cells had
      high expression of the IL-7 receptor alpha-chain CD127 and did not contain the
      neurotoxic cytolytic enzymes perforin, granzyme A, and granzyme B. We postulate
      that CNS T cells make up a population of tissue-adapted differentiated cells,
      which use CX3CR1 and CXCR3 to home into the perivascular space, use IL-7 for
      maintenance, and lack immediate cytolytic activity, thereby preventing
      immunopathology in response to low or non-specific stimuli. The presence of these
      cells in this tightly regulated environment likely enables a fast response to
      local threats. Our results will enable future detailed exploration of T-cell
      subsets in the brain involved in neurological diseases. 

PMID- 23880788
TI  - A liquid-crystalline perylene tetracarboxylic bisimide derivative bearing a
      triethylene oxide chain and complexation of the derivative with Li cations.
AB  - A liquid-crystalline (LC) perylene tetracarboxylic bisimide (PTCBI) derivative
      bearing a triethylene oxide chain as well as two pentamethyldisiloxane chains was
      synthesized. This compound exhibits an ordered lamellar phase at room
      temperature, and the LC phase is retained when the sample is cooled to -100 
      degrees C. Due to the presence of extended pi-conjugated perylene rings,
      efficient electron transport occurs in the lamellar phase and the electron
      mobility exceeds 1 * 10(-3) cm(2) V(-1) s(-1) at room temperature. Moreover, this
      PTCBI derivative can form a complex with lithium triflate because of the polar
      triethylene oxide chain. Lithium triflate can be mixed with it up to 3 mol%. Up
      to this concentration, the lamellar LC structure and the electron transport
      properties are not perturbed by the presence of the ionic species. 

PMID- 23880789
TI  - Mesenchymal stem cell transplantation may provide a new therapy for
      ultrafiltration failure in chronic peritoneal dialysis.
AB  - BACKGROUND: The purpose of this study was to investigate possible healing effects
      of intraperitoneal (IP) mesenchymal stem cell (MSC) transplantation on
      ultrafiltration failure (UFF) in a chronic rat model of peritoneal dialysis (PD).
      METHODS: Rats were initially divided into two groups. The APUF group received
      once-daily IP injections of 20 mL of 3.86% glucose PD solution for 6 weeks to
      stimulate the development of UFF and a control group received noinjections. The
      PUF group was sub-divided into three groups: a PUF-C group, an MSC group and a
      Placebo (P) group. Peritoneal equilibration tests (PETs) and peritoneal biopsies
      were performed in the control and PUF-C groups. MSCs were administered by IP
      injection in the MSC group and the PUF-C and P groups received IP injection of
      placebo. PETs and peritoneal biopsies were performed in the MSC and P groups at
      the first [P-1 (and MSC-1 groups] and second [P-2 and MSC-2 groups] week after
      receiving MSCs or placebo. RESULTS: When compared with the control group,
      ultrafiltration capacity significantly decreased and the submesothelial thickness
      increased in the PUF-C and P groups (P-1, P-2) (P < 0.05), but there were no
      differences between the control and MSC groups (MSC-1, MSC-2). The rate of
      glucose transport was high in the PUF-C and P-2 groups compared with the control
      group, and D/PCr rates in the PUF-C and P-2 groups were lower than in the control
      group (P < 0.05). However, D/D0(glucose) was higher and D/P(Cr)was lower in the
      MSC-2 group than in the PUF-C and P-2 groups (P < 0.05). Transforming growth
      factor-beta (TGF-beta) levels were lower in the MSC groups than in the P and PUF
      C groups (P < 0.05). CONCLUSION: The PUF-C group had a high permeability UFF.
      These results showed that MSC transplantation exerted positive effects on UFF in
      a chronic rat model of PD. MSC transplantation may provide new options for the
      renewal of the peritoneum in chronic PD patients with UFF.

PMID- 23880790
TI  - Heparin/heparan sulphate interactions with complement--a possible target for
      reduction of renal function loss?
AB  - Current management of end-stage renal failure is based on renal replacement
      therapy by dialysis or transplantation. Increased occurrence of renal failure in
      both native and transplanted kidneys indicates a need for novel therapies to stop
      or limit the progression of the disease. Acute kidney injury and proteinuria are
      major risk factors in the development of renal failure. In this regard, innate
      immunity plays an important role in the pathogenesis of renal diseases in both
      native and transplanted kidneys. The complement system is a major humoral part of
      innate defense. Next to the well-known complement activators, quite a number of
      the complement factors react with proteoglycans (PGs) both on cellular membranes
      and in the extracellular compartment. Therefore, these interactions might serve
      as targets for intervention. In this review, the current knowledge of
      interactions between PGs and complement is reviewed, and additionally the options
      for interference in the progression of renal disease are discussed. 

PMID- 23880791
TI  - Enhancement of phase separation and superconductivity in Mn-doped K0.8Fe2-yMnySe2
      crystals.
AB  - Single crystals of K0.8Fe2-yMnySe2 with slight Mn doping have been grown by a
      self-flux method. X-ray diffraction measurements show enhanced phase separation
      with increasing Mn doping in the compounds. The superconducting transition
      temperature increases to Tc,onset ~ 46.1 K for the sample with y ~ 0.03, as
      observed by electrical transport measurements. Our results demonstrate that the
      doping of Mn does not suppress the superconductivity, and on the contrary
      increases the superconducting shield fraction and transition temperature, an
      effect which may originate from the Mn dopant's high preference to fill into iron
      vacancies in the Mn-doped samples. It suggests that the Mn dopant can induce a
      local lattice strain or distortion that profitably modifies the microstructure of
      the superconducting/metallic phase, leading to superconductivity of the compound.

PMID- 23880792
TI  - A unique signal distorts the perception of species richness and composition in
      high-throughput sequencing surveys of microbial communities: a case study of
      fungi in indoor dust.
AB  - Sequence-based surveys of microorganisms in varied environments have found
      extremely diverse assemblages. A standard practice in current high-throughput
      sequence (HTS) approaches in microbial ecology is to sequence the composition of
      many environmental samples at once by pooling amplicon libraries at a common
      concentration before processing on one run of a sequencing platform. Biomass of
      the target taxa, however, is not typically determined prior to HTS, and here, we
      show that when abundances of the samples differ to a large degree, this standard
      practice can lead to a perceived bias in community richness and composition.
      Fungal signal in settled dust of five university teaching laboratory classrooms,
      one of which was used for a mycology course, was surveyed. The fungal richness
      and composition in the dust of the nonmycology classrooms were remarkably similar
      to each other, while the mycology classroom was dominated by abundantly
      sporulating specimen fungi, particularly puffballs, and appeared to have a lower
      overall richness based on rarefaction curves and richness estimators. The fungal
      biomass was three to five times higher in the mycology classroom than the other
      classrooms, indicating that fungi added to the mycology classroom swamped the
      background fungi present in indoor air. Thus, the high abundance of a few taxa
      can skew the perception of richness and composition when samples are sequenced to
      an even depth. Next, we used in silico manipulations of the observed data to
      confirm that a unique signature can be identified with HTS approaches when the
      source is abundant, whether or not the taxon identity is distinct. Lastly,
      aerobiology of indoor fungi is discussed. 

PMID- 23880793
TI  - Disentangling mechanisms involved in the adaptation of photosynthetic
      microorganisms to the extreme sulphureous water from Los Banos de Vilo (S Spain).
AB  - Los Banos de Vilo (S Spain) is a natural spa characterized by extreme sulphureous
      waters; however, populations of chlorophyceans inhabit in the spa. The adaptation
      mechanisms allowing resistance by photosynthetic microorganisms to the extreme
      sulphureous waters were studied by using a modified Luria-Delbruck fluctuation
      analysis. For this purpose, the adaptation of the chlorophycean Dictyosphaerium
      chlorelloides and the cyanobacterium Microcystis aeruginosa (both isolated from
      non-sulphureous water) were analysed in order to distinguish between
      physiological adaptation (acclimation) and genetic adaptation by the selection of
      rare spontaneous mutations. Acclimation to the extreme water was achieved by D.
      chlorelloides; however, M. aeruginosa cells proliferated as a consequence of
      selection of favoured mutants (i.e. genetic adaptation). The resistant cells of
      M. aeruginosa appeared with a frequency of 7.1 * 10(-7) per cell per generation,
      and the frequency of the resistant allele, under non-selective conditions, was
      estimated to be 1.1 * 10(-6) per cells as a consequence of the balance mutation
      selection. It could be hypothesized that the populations of eukaryotic algae
      living in the Los Banos de Vilo could be the descendants of chlorophyceans that
      arrived fortuitously at the spa in the past. On the other hand, cyanobacteria
      could quickly adapt by the selection of favoured mutants. The single mutation
      that allows resistance to sulphureous water from Banos de Vilo in M. aeruginosa
      represents a phenotypic burden impairing growth rate and photosynthetic
      performance. The resistant-variant cells of M. aeruginosa showed a lower
      acclimated growth rate and a decreased maximum quantum yield and photosynthetic
      efficiency, in comparison to the wild-type cells. 

PMID- 23880794
TI  - How well do different measurement modalities estimate the number of vasomotor
      symptoms? Findings from the Study of Women's Health Across the Nation FLASHES
      Study.
AB  - OBJECTIVE: Studies of vasomotor symptoms (VMS) typically measure VMS via daily
      diaries completed at the end of the day. VMS can also be measured via diaries
      completed throughout the day or via physiological monitors-modalities with lower
      recall demands. We examined the degree of correspondence between three VMS
      measurement modalities: retrospective end-of-day/morning diaries, prospective
      reporting, and physiological monitoring. We determined whether discrepancies
      between measurement modalities varied by participant characteristics. METHODS:
      Twenty-five African-American women and 27 white women from the Pittsburgh site of
      the Study of Women's Health Across the Nation who were experiencing VMS, had
      intact uterus and ovaries, and were free of medications affecting VMS underwent 4
      days of ambulatory VMS and Actiwatch monitoring. VMS were recalled in end-of-day
      and morning diaries, reported prospectively during the day, and measured
      physiologically via a hot flash monitor. Associations between anxiety, sleep, or
      race/ethnicity and VMS measurement modality difference scores were examined using
      generalized estimating equations. RESULTS: Women underestimated the number of
      daytime VMS at the end of the day as compared with VMS that were prospectively
      reported or physiologically measured throughout the day. This pattern was
      particularly pronounced among African-American women (b [SE] = -3.01 [0.93], P =
      0.001) and women with higher anxiety (b [SE] = -3.13 [1.53], P = 0.04). For
      nighttime VMS, women overestimated the number of VMS in the morning upon waking
      as compared with prospective measures, particularly if they had poorer sleep
      (higher wakening after sleep onset: b [SE] = 0.03 [0.008], P = 0.001).
      CONCLUSIONS: Different measurement modalities yield different VMS estimates.
      Negative affect, sleep, and race/ethnicity may affect the recall of VMS.

PMID- 23880795
TI  - Over-the-counter treatments and perineal hygiene in postmenopausal women.
AB  - OBJECTIVE: The objective of this descriptive study was to quantify the personal
      hygiene habits/practices of, as well as the over-the-counter (OTC) products used
      by, postmenopausal women. Specifically, we were interested in any product that
      would contact the vulva or vagina. METHODS: We performed a cross-sectional study
      of postmenopausal women seeking routine gynecologic care. We developed a
      questionnaire on their personal hygiene habits/practices and the OTC products
      that they use that would contact the vulva or vagina. We recruited postmenopausal
      women seeking gynecologic care from two separate gynecology practices.
      Descriptive statistics were performed as appropriate to characterize the
      frequency of reported treatments and practices. RESULTS: The questionnaire on OTC
      treatments and perineal hygiene was completed by 114 postmenopausal women. Fifty
      eight women (50.9%) reported using at least one OTC vulvovaginal treatment in the
      last 3 months, including barrier treatments, topical anesthetics, powders, and
      antifungals. Women often used more than one OTC product. Thirty-seven women
      (32.5%) reported the use of two or more OTC products. Powders were used by 34
      women (29.8%). Talcum powder was the most commonly used powder (26 of 34; 76.5%).
      Nine postmenopausal women (7.9%) reported douching in the last 3 months.
      CONCLUSIONS: We found that more than half of postmenopausal women seeking
      gynecologic care have used an OTC product for vulvovaginal symptoms in the last 3
      months and that one third of women use two or more products. Because the use of
      OTC products is very common, our study highlights the need for a detailed history
      inquiry about OTC product use and perineal hygiene practices.

PMID- 23880796
TI  - Calcium supplements: do they help or harm?
AB  - Current recommendations for calcium intake call for 1,000 mg per day for women
      ages 19-50 and 1,200 mg per day for women over age 50 to ensure bone health.
      Given recent concerns that calcium supplements may raise risk for cardiovascular
      disease and kidney stones, women should aim to meet this recommendation primarily
      by eating a calcium-rich diet and taking calcium supplements only if needed to
      reach the RDA goal (often only approximately 500 mg per day in supplements is
      required).

PMID- 23880797
TI  - Ovarian conservation versus bilateral oophorectomy at the time of hysterectomy
      for benign disease.
AB  - Observational studies suggest that elective bilateral oophorectomy may do more
      harm than good. Removing the ovaries at the time of hysterectomy for benign
      disease should be approached with caution, especially for women younger than age
      50. For women who choose oophorectomy, some evidence suggests that menopausal
      estrogen therapy may ameliorate some of the increased risk. An informed consent
      process covering the risks and benefits of both oophorectomy and ovarian
      conservation is important. 

PMID- 23880799
TI  - Albuminuria and management of type 2 diabetes mellitus.

PMID- 23880800
TI  - Rituximab in the treatment of nephrotic syndrome: a systematic review.
AB  - Recently, the role of B cells in the pathogenesis of nephrotic syndrome is
      explained by some researchers. It has also been shown that the anti-CD20
      antibody, rituximab, may be an option in the treatment of these patients. In this
      systematic review, we performed extensive search and identified studies on
      rituximab use in children with nephrotic syndrome. There are some case reports as
      well as larger series in this regard. The majority of these case reports and
      series have demonstrated the success of rituximab in the treatment of nephrotic
      syndrome, especially in pediatric patients with steroid-dependent and frequent
      relapsing nephrotic syndrome. Nevertheless, the treatment strategies before and
      after rituximab infusion are not clear to date. On the other hand, it is believed
      that positive results on rituximab use in nephrotic syndrome are much more
      reported by researchers than the negative results and this is an important bias.
      Although most reports on rituximab use in pediatric patients have not recognized
      significant side effects, the long-term adverse events of rituximab are not
      known. Thus, controlled long-term studies are required to be done to assess the
      risk-benefit profile of rituximab in childhood nephrotic syndrome. 

PMID- 23880798
TI  - No association between germline variation in catechol-O-methyltransferase and
      colorectal cancer survival in postmenopausal women.
AB  - OBJECTIVE: Sex steroid hormones play a role in colorectal cancer (CRC)
      development, but little is known about their influence on tumor progression and
      metastasis. Because catechol-O-methyltransferase (COMT; 22q11.21) activity is an
      important component of estrogen-mediated carcinogenesis, we hypothesized that
      germline variation in COMT may be associated with CRC survival. METHODS: We
      identified 10 single nucleotide polymorphisms that tagged variation across two
      isoforms of COMT in 2,458 women with CRC from the Nurses' Health Study,
      Postmenopausal Hormones Supplementary Study to the Colon Cancer Family Registry,
      VITamins And Lifestyle Study, and Women's Health Initiative. All four studies
      participated in the Genetics and Epidemiology of Colorectal Cancer Consortium.
      RESULTS: During a median follow-up of 7 years across all studies, there were 799
      deaths, including 566 deaths from CRC. Based on multiple comparisons, no
      associations between single nucleotide polymorphisms and CRC-specific or overall
      survival reached statistical significance, including the well-characterized
      Val108/158Met polymorphism (rs4680; CRC-specific survival: hazard ratio per minor
      allele, 1.04; 95% CI, 0.92-1.17; overall survival: hazard ratio per minor allele,
      1.01; 95% CI, 0.90-1.14). CONCLUSIONS: In this large study of women with CRC, we
      find no evidence that common inherited variation in COMT is associated with
      survival time after diagnosis.

PMID- 23880801
TI  - Focal segmental glomerulosclerosis and kidney transplantation.
AB  - The recurrence rate of focal segmental glomerulosclerosis after kidney
      transplantation is ranging between 20% and 40%. Focal segmental
      glomerulosclerosis is associated with poor graft survival. In this review, the
      etiology, pathogenesis, clinicopathological features, risk factors of recurrence,
      and updated lines of management are discussed. 

PMID- 23880802
TI  - Hypercalciuria in school-aged children of Rasht: a single-center study.
AB  - Hypercalciuria is the most common identifiable metabolic cause of calcium kidney
      calculus disease. Idiopathic hypercalciuria is defined as hypercalciuria with
      normal serum electrolytes levels in the absence of any known underlying disease
      responsible for increased urinary calcium excretion. The aim of the present
      survey was to study the prevalence of urinary tract signs and symptoms of
      idiopathic hypercalciuria in a healthy group of primary school children living in
      Rasht, a city in north of Iran. The prevalence of idiopathic hypercalciuria in
      our study was estimated to be 5.6%. This is a first report of idiopathic
      hypercalciuria in Guilan province. 

PMID- 23880803
TI  - Albuminuria and its correlates in type 2 diabetic patients.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of
      albuminuria and its correlates and investigate disease management for patients
      with type 2 diabetes mellitus in Ahvaz. MATERIALS AND METHODS: This was a cross
      sectional study on the 350 patients with type 2 diabetes mellitus attending the
      Diabetes Clinic at Golestan Hospital, from October 2010 to September 2011.
      Demographic characteristics were recorded and height, weight, and blood pressure
      were measured. Blood urea nitrogen and serum levels of creatinine, total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, triglyceride, and glycosylated hemoglobin A were measured in fasting
      blood samples. Spot urine and 24-hour urine collection were tested for albumin
      and kidney ultrasonography was done. RESULTS: A total of 72 of 350 patients
      (20.6%) had microalbuminuria and 18 (5.1%) had macroalbuminuria. Elevated serum
      creatinine was seen in 6.9% and azotemia in 6.0%. In multivariable analysis,
      blood urea nitrogen level, glycosylated hemoglobin A, and duration of diabetes
      mellitus were associated with urinary albumin excretion (P = .04). A small
      proportion of the participants achieved optimal treatment goals for modifiable
      risk factors. CONCLUSIONS: Abnormal urinary albumin excretion is seen in one
      quarter of type 2 diabetic patients and a small but important number of them have
      azotemia. Albuminuria was found to be associated with long-term duration of
      diabetes mellitus, poor glucose control (revealed by high glycosylated hemoglobin
      A levels), and high blood urea nitrogen. Poor glycemic control may have a
      significant role in the progression of diabetic nephropathy in these patients.

PMID- 23880804
TI  - Urinary adrenomedullin level in children with acute pyelonephritis before and
      after treatment.
AB  - INTRODUCTION: Adrenomedullin (AM) is a 52-amino acid peptide that causes
      vasodilatation by increased synthesis of nitric oxide. Its production by
      different cells such as cardiac myocytes, smooth muscle, endothelial, and
      oncogenic cells is stimulated by inflammatory processes. It has been shown that
      in the presence of inflammation in the urinary system, concentration of AM
      increases. In this study, we measured urinary AM in children with acute
      pyelonephritis before and after treatment and compared its level with that in
      healthy children. MATERIALS AND METHODS: In a case-control study, 31 children
      with clinical and paraclinical documentation of pyelonephritis (case group) and
      30 healthy children without pyelonephritis or other infections (control group)
      were studied. Urinary AM were measured on spot urine samples by high-performance
      liquid chromatography, and creatinine was measured by spectrophotometry to report
      the AM-creatinine ratio. RESULTS: Urinary AM-creatinine ratios were 61.3 +/-
      119.4 pg/mg and 4.26 +/- 11.4 pg/mg, respectively, in the case and control groups
      (P = .01). After treatment of pyelonephritis in the patients of the case group,
      this ratio decreased to 13.1 +/- 21.9 (P = .048). The coefficient correlation
      between urinary AM and leukocytes count was 0.252 (P = .17). Urinary AM levels
      were 1896 +/- 1748 pg/dL and 391 +/- 477 pg/dL in the patients with 4+ versus
      negative C-reactive protein levels, respectively (P = .008). CONCLUSIONS: Urinary
      AM increases in the course of pyelonephritis and decreases significantly after
      treatment.

PMID- 23880805
TI  - Prevalence of childhood obesity and hypertension in south of Iran.
AB  - INTRODUCTION: Obesity is a growing problem worldwide and is likely a major cause
      of the increased prevalence of high blood pressure in children. The aim of this
      study was to investigate the frequency of pediatric obesity and its association
      with hypertension in a sample of children and adolescents in Fars province (south
      of Iran). MATERIALS AND METHODS: This cross-sectional study was carried out in
      Shiraz during a period from 2010 to 2011. A total of 2000 healthy students aged
      11 to 17 years were included. Data on weight, height, systolic and diastolic
      blood pressure (measured 3 times with 5-minute intervals), and parental history
      of hypertension and educational level were obtained. The 95th percentile body
      mass index for age and sex was considered obesity. RESULTS: Overall, 7% and 11.8%
      of the students were obese and hypertensive, respectively. Blood pressure was
      associated with body mass index. Maternal education level was not associated with
      hypertension in the child. CONCLUSIONS: In this study, obesity was an important
      risk factor for hypertension. Our data showed that prevalence of obesity has not
      been changed in the recent 5 years in Iran, but that of hypertension has risen
      significantly. The high prevalence of hypertension in overweight and obese
      children emphasizes the need for prevention and control of childhood obesity and
      hypertension in early stages.

PMID- 23880806
TI  - Protective effects of Rosa canina L fruit extracts on renal disturbances induced
      by reperfusion injury in rats.
AB  - INTRODUCTION: This study aimed to investigate the effects of Rosa canina L fruit
      extracts on histological damages, oxidative stress, and functional disturbances
      induced by bilateral renal ischemia and reperfusion. MATERIALS AND METHODS:
      Ischemia and reperfusion were induced on the kidneys of anesthetized male Sprague
      Dawley rats. The rats in the reperfusion and Rosa canina groups were administered
      extract solvent and Rosa canina extract, respectively. In addition, in the sham
      group, surgery was done without ischemia. In the last 6 hours of the reperfusion
      period, urine sample were collected using metabolic cage and at the end of this
      period, blood samples were taken from the descending aorta. The kidney tissues
      were collected and subjected to microscopic study for histological damages, while
      oxidative stress was measured by determining malondialdehyde and ferric
      reducing/antioxidant power levels. RESULTS: The comparison between the
      reperfusion and sham groups indicated reductions in creatinine clearance,
      absolute excretion of potassium, urine osmilarity, and increase in absolute
      excretion of sodium in the reperfusion group. These changes were less pronounced
      with Rosa canina fruit extract. In addition, blood creatinine and urea
      concentrations which increased in the reperfusion group, were significantly lower
      in the Rosa canina group. In this group, the degree of histological damages and
      the level of malondialdehyde were lower than the reperfusion group, while ferric
      reducing/antioxidant power level was significantly higher. CONCLUSIONS: The
      findings of this study showed that Rosa canina fruit extract possesses protective
      effects against kidney function disturbances, oxidative stress, and histological
      damages.

PMID- 23880807
TI  - Ambulatory blood pressure monitoring for children with beta-thalassemia major: a
      preliminary report.
AB  - INTRODUCTION: Heart disease is one of the most common reasons of death in beta
      thalassemia major. A few studies have been done in children about blood pressure
      changes. The aim of this study was to assess hemodynamic changes by ambulatory
      blood pressure monitoring (ABPM). MATERIALS AND METHODS: In this cross-sectional
      study, 30 patients with beta-thalassemia major aged 5 to 18 years old were
      evaluated with 24-hour ABPM. The exclusion criteria were an ejection Fraction
      less than 50% and a glomerular filtration rate less than 90 mL/min/1.73 m2.
      Hypertension was defined as a mean blood pressure index of 1 and greater with or
      without load blood pressure greater than 25%. Dipper status was defined as a 10%
      decrease in nighttime versus daytime mean arterial blood pressure. RESULTS: High
      blood pressure was detected in 16.7% of the patients. The whole-day ABPM showed
      hypertension in 6.7% of the children. During daytime measurements, systolic
      hypertension was seen in 3.3% (load 3.7%) and diastolic in 6.7% (load 3.3%).
      These figures for nighttime evaluation were 6.7% (load 3.3%) and 10.3% (load
      6.9%), respectively. Nondipper status was detected in 56.7% of the children.
      There was no significant correlation between abnormal blood pressure and age,
      sex, body mass index, hemoglobin, number or rates of blood transfusion, or serum
      ferritin level. CONCLUSIONS: The ABPM may be a useful instrument for early
      detection of hemodynamic changes in children with beta-thalassemia major.

PMID- 23880808
TI  - Adiponectin as a novel indicator of malnutrition and inflammation in hemodialysis
      patients.
AB  - INTRODUCTION: Protein-energy malnutrition and inflammation are common and
      overlapping conditions in hemodialysis patients, which are associated with
      increased risk of morbidity and mortality. Adiponectin is an adipocytokine
      exclusively produced by adipose tissue. The aim of this study was to further
      elucidate the association between serum adiponectin levels and the nutritional
      status of hemodialysis patients. MATERIALS AND METHODS: Seventy-three patients on
      hemodialysis for at least 3 months, three times weekly, without any acute
      illness, were divided into 2 groups of well-nourished (n = 25) and malnourished
      (n = 48) based on their nutritional status, measured by the subjective global
      assessment. Serum levels of adiponectin, albumin, blood urea nitrogen, and
      creatinine; body mass index; and the malnutrition-inflammation score were
      measured in all patients. These values were compared between well-nourished and
      malnourished patients. The correlations of nutritional variables with serum
      levels of adiponectin were determined, as well. RESULTS: Except for the
      malnutrition-inflammation score, which was significantly higher in the
      malnourished patients compared to the well-nourished ones (11.1 +/- 3.6 versus
      4.2 +/- 2.0, P < .001), no other significant differences were found between the
      two groups. A weak but significant positive correlation was found between the
      serum levels of adiponectin and subjective global assessment scores (r = 0.25, P
      = .03). CONCLUSIONS: The results of our study point to potential utility of serum
      adiponectin level as an indicator of nutritional status in hemodialysis patients.
      Further studies are needed to clarify the role of adiponectin in the pathogenesis
      of malnutrition in hemodialysis patients.

PMID- 23880809
TI  - Conversion to sirolimus in kidney transplant recipients: a single-center study.
AB  - INTRODUCTION: As an immunosuppressive treatment, cyclosporine carries a
      significant risk of nephrotoxicity. In this study, we assessed the safety and
      efficacy of sirolimus conversion in our kidney transplant recipients. MATERIALS
      AND METHODS: Sirolimus conversion in 99 kidney transplant recipients was
      evaluated. Serum level of creatinine, glomerular filtration rate (GFR), and the
      occurrence of adverse effects of sirolimus were evaluated at conversion time and
      1, 6, 12, 24, and 36 months after conversion. RESULTS: The major causes of
      conversion were chronic allograft nephropathy and cyclosporine nephrotoxicity.
      The median time to conversion and follow-up were 54.7 months and 24 months,
      respectively. Three patients died during the study period. The acute rejection
      rate was 4%. In 16.6% of the patients, sirolimus was discontinued because of
      refractory adverse effects. No significant changes in estimated GFR and incidence
      of adverse effects were observed between patients with baseline estimated GFR
      lower or higher than 40 mL/min. Patients with early sirolimus conversion (less
      than 6 months after transplant) had improvement of their GFR (59.9 +/- 22.3
      mL/min to 68.0 +/- 15.5 mL/min, P = .02), while kidney recipients with late
      conversion did not show such an improvement. The difference between GFRs in these
      two groups reached significant level at 12 months and stayed significant until
      the end of the follow-up. CONCLUSIONS: This study emphasizes that conversion of
      cyclosporine to sirolimus could be associated with stable kidney allograft
      function. However, cyclosporine discontinuation should be considered early when
      it is indicated.

PMID- 23880810
TI  - Parapharengeal unicentric Castleman disease with nephrotic syndrome.
AB  - Castleman disease (CD) is a rare lymphoproliferative disorder, first described in
      1956. This case report describes a 27-year-old man with hyaline vascular
      unicentric CD, first presented with edema and hypertension. On initial evaluation
      for edema, 24-hour urine collection revealed 8200 mg/24 h protein excretion.
      Pathologic examination of the kidney specimen showed diffuse mesangial lesions
      with segmental subepithelial deposition. On follow-up for nephrotic syndrome, the
      patient experienced a feeling of a mass in his pharynx and deterioration of
      previous snoring, documented by neck magnetic resonance imaging. Pathology report
      of the excisional biopsy showed CD. Treatment with corticosteroids and partial
      excision can be considered as an alternative to surgery for unresectable
      unicentric CD. The 5-year follow-up showed that this strategy could lead to
      remission. 

PMID- 23880811
TI  - Atypical clinical course of antineutrophil cytoplasmic autoantibodies-associated
      vasculitis.
AB  - We report a 16-year-old previously healthy boy who was admitted to hospital with
      fever, constitutional symptoms, purpura, additive arthritis, dysentery, rapid
      progressive renal failure, resembling Henoch- Schuenlein purpura, accompanied
      with retropharyngeal abscess. Kidney biopsy revealed rapid progressive
      glomerulonephritis with crescent formation, without immune deposition in immune
      fluorescent study. Serologic study revealed positive proteinase antineutrophil
      cytoplasmic antibody (ANCA). Intravenous methyl prednisolone plus and
      cyclophosphamide pulse were administered with a diagnosis of ANCA-associated
      vasculitis. Serum creatinine level reduced during the treatment and the patients
      was discharged with good clinical condition. This was the first case in which the
      ANCA-associated vasculitis was presented with retropharyngeal abscess. Other
      unusual findings were bloody diarrhea, raised purpura, and additive arthritis in
      an adolescence, which are more characteristic for Henoch-Schuenlein purpura. 

PMID- 23880812
TI  - Benign pheochromocytoma presented 6 years after kidney transplantation.
AB  - Hypertension is very common in kidney transplant patients; however, severe and
      resistant cases should raise suspicion of secondary causes. Pheochromocytomas are
      rare but serious tumors because of their lethal hypertensive and possible
      malignant nature. The diagnosis is occasionally elusive, but prompt diagnosis and
      localization is essential for definitive surgical management. We report a case of
      a patient with benign pheochromocytoma presenting largely asymptomatically, but
      with severe resistant hypertension, 6 years after kidney transplantation. To the
      best of our knowledge, this is the first case report of this type of tumor after
      kidney transplantation. 

PMID- 23880813
TI  - Hyperkalemia in children with nephrotic syndrome.

PMID- 23880814
TI  - Potential protective effect of grape seed proanthocyanidine extract in cold
      ischemia-reperfusion injury of the transplanted kidney.

PMID- 23880815
TI  - Re: hyperglycemia after kidney transplantation: frequency and risk factors.

PMID- 23880816
TI  - Re: effect of erythropoietin on kidney allograft survival: early use after
      transplantation.

PMID- 23880817
TI  - Re: self-esteem in Greek dialysis patients: the contribution of health locus of
      control.

PMID- 23880818
TI  - The great escape: Active genes on inactive sex chromosomes and their evolutionary
      implications.
AB  - Epigenetic mechanisms precisely regulate sex chromosome inactivation as well as
      genes that escape the silencing process. In male germ cells, DNA damage response
      factor RNF8 establishes active epigenetic modifications on the silent sex
      chromosomes during meiosis, and activates escape genes during a state of sex
      chromosome-wide silencing in postmeiotic spermatids. During the course of
      evolution, the gene content of escape genes in postmeiotic spermatids recently
      diverged on the sex chromosomes. This evolutionary feature mirrors the epigenetic
      processes of sex chromosomes in germ cells. In this article, we describe how
      epigenetic processes have helped to shape the evolution of sex chromosome-linked
      genes. Furthermore, we compare features of escape genes on sex chromosomes in
      male germ cells to escape genes located on the single X chromosome silenced
      during X-inactivation in females, clarifying the distinct evolutionary
      implications between male and female escape genes.

PMID- 23880819
TI  - Experience of symptoms indicative of gynaecological cancers in UK women.
AB  - BACKGROUND: Gynaecological cancers account for ~12% of female cancer incidence in
      the United Kingdom. Encouraging prompt help-seeking for potential symptoms could
      help improve outcomes. However, before developing help-seeking interventions, it
      is important to estimate the number of women with symptoms potentially indicative
      of a gynaecological cancer to help estimate the impact of such interventions on
      primary care. METHODS: As part of a face-to-face, population-based survey, women
      aged >=16 (n=911) were shown a list of symptoms potentially indicative of a
      gynaecological cancer and were asked to indicate any experienced in the last 3
      months. Those who reported symptoms were asked about their responses to one
      randomly selected index symptom. RESULTS: Just under half (44%) of the
      respondents reported a symptom, with 35% reporting a frequent and/or severe
      symptom. Younger (P<0.001), lower socioeconomic status (P<0.01) and non-White
      women (P<0.05) were significantly more likely to report symptoms. Few (14%)
      respondents were both older (>=45 years) and had a frequent and/or severe
      symptom. Of these women, 38% had seen a GP. CONCLUSION: Symptoms that potentially
      indicate a gynaecological cancer, even if limited to those that are frequent
      and/or severe, appear to be common. Consequently, encouraging prompt help-seeking
      may increase the burden on primary care. However, targeting those at increased
      risk (older women with frequent or severe symptoms) should avoid unmanageable
      increases in primary care consultations for gynaecological conditions.

PMID- 23880820
TI  - A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM
      398) for patients with gemcitabine-refractory metastatic pancreatic cancer.
AB  - BACKGROUND: PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that
      has improved pharmacokinetics and tumour bio-distribution of the free drug. This
      phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic
      cancer. METHODS: Patients who had metastatic pancreatic adenocarcinoma, Karnofsky
      performance status >=70, and had progressed following gemcitabine-based therapy
      were eligible. Intravenous injection of PEP02 120 mg m(-2) was given every 3
      weeks. Simon 2-stage design was used. The primary objective was 3-month survival
      rate (OS(3-month)). RESULTS: A total of 40 patients were enrolled. The most
      common severe adverse events included neutropenia, abdominal pain, asthenia, and
      diarrhoea. Three patients (7.5%) achieved an objective response, with an
      additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles.
      Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker
      decline. The study met its primary end point with an OS(3-month) of 75%, with
      median progression-free survival and overall survival of 2.4 and 5.2 months,
      respectively. CONCLUSION: PEP02 demonstrates moderate antitumour activity with a
      manageable side effect profile for metastatic, gemcitabine-refractory pancreatic
      cancer patients. Given the limited treatment options available to this patient
      population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is
      currently underway.

PMID- 23880821
TI  - The association of coffee intake with liver cancer incidence and chronic liver
      disease mortality in male smokers.
AB  - BACKGROUND: Coffee intake is associated with reduced risk of liver cancer and
      chronic liver disease as reported in previous studies, including prospective ones
      conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C
      viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western
      populations with lower HBV and HCV prevalence are sparse. Also, although
      preparation methods affect coffee constituents, it is unknown whether different
      methods affect disease associations. METHODS: We evaluated the association of
      coffee intake with incident liver cancer and chronic liver disease mortality in
      27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene
      Cancer Prevention Study, who recorded their coffee consumption and were followed
      up to 24 years for incident liver cancer or chronic liver disease mortality.
      Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were
      estimated by Cox proportional hazard models. RESULTS: Coffee intake was inversely
      associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73
      0.93; P-trend across categories=0.0007) and mortality from chronic liver disease
      (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in
      those without diabetes, HBV- and HCV-negative cases, and in analyses stratified
      by age, body mass index, alcohol and smoking dose. We observed similar
      associations for those drinking boiled or filtered coffee. CONCLUSION: These
      findings suggest that drinking coffee may have benefits for the liver,
      irrespective of whether coffee was boiled or filtered.

PMID- 23880822
TI  - Weight change in adulthood and risk of postmenopausal breast cancer: the HUNT
      study of Norway.
AB  - BACKGROUND: Adult weight gain is associated with increased risk of postmenopausal
      breast cancer. Most previous studies are limited by using recalled or self
      reported data, and it is not known if age-specific weight changes are important
      for breast cancer risk. METHODS: In a Norwegian cohort of 28,153 women (and 900
      incident breast cancers) with longitudinal anthropometric measurements over up to
      30 years, we studied both overall and age-related weight changes in adulthood and
      risk of postmenopausal breast cancer. RESULTS: Overall, weight gain in adulthood
      was associated with increased breast cancer risk (hazard ratio (HR) per kg per
      year 1.31, 95% confidence interval (CI) 1.11-1.54). Weight gain before (HR per kg
      per year 1.38, 95% CI 1.09-1.75) or around menopause (1.69, 95% CI 1.32-2.16) was
      associated with increased risk, but there was no clear risk increase associated
      with later weight gain (HR per kg per year 0.92, 95% CI 0.73-1.18). CONCLUSION:
      Weight gain in adulthood was associated with increased risk of breast cancer. Our
      results suggest that weight gain before and around menopausal age may be
      particularly important for breast cancer risk among postmenopausal women.

PMID- 23880823
TI  - Characterisations of human prostate stem cells reveal deficiency in class I UGT
      enzymes as a novel mechanism for castration-resistant prostate cancer.
AB  - BACKGROUND: Evidence increasingly supports that prostate cancer is initiated by
      the malignant transformation of stem cells (SCs). Furthermore, many SC-signalling
      pathways are shown to be shared in prostate cancer. Therefore, we planned
      transcriptome characterisation of adult prostate SCs as a strategy to consider
      new targets for cancer treatment. METHODS: Intuitive pathway analysis was used
      for putative target discovery in 12 matched selections of human prostate SCs,
      transiently amplifying cells and terminally differentiated cells. These were
      pooled into three groups according to the stage of differentiation for mRNA
      microarray analysis. Targets identified were validated using uncultured primary
      tissue (n=12), functional models of prostate cancer and a tissue microarray
      consisting of benign (n=42) and malignant prostate (n=223). RESULTS: A deficiency
      in class 1 UDP glucuronosyltransferase (UGT) enzymes (UGT1A) was identified in
      prostate SCs, which are involved in androgen catabolism. Class 1 UGT enzyme
      expression was also downregulated in cancer SCs and during progression to
      metastatic castration-resistant prostate cancer (CRPC). Reduction of UGT1A
      expression in vitro was seen to improve cell survival and increase androgen
      receptor (AR) activity, as shown by upregulation of prostate-specific antigen
      expression. INTERPRETATION: Inactivation of intracellular androgen catabolism
      represents a novel mechanism to maintain AR activity during CRPC.

PMID- 23880824
TI  - Sorafenib for advanced hepatocellular carcinoma (HCC): impact of rationing in the
      United Kingdom.
AB  - BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) is dependent upon
      tumour stage, performance status (PS), severity of underlying liver disease, and
      the availability of appropriate therapies. The unavailability of sorafenib may
      have a significantly adverse effect on the prognosis of UK patients with advanced
      HCC. During the study period, access to sorafenib was at the discretion of local
      health funding bodies, a process that may delay or deny access to the drug and
      that remains in place for Wales, Scotland, and Northern Ireland. Here, we attempt
      to address the impact of this system on patients with advanced HCC in the United
      Kingdom. METHODS: This is a retrospective study performed in the two largest
      specialist hepatobiliary oncology units in the United Kingdom. Funding
      applications were made to local funding bodies for patients with advanced HCC for
      whom sorafenib was considered appropriate (advanced HCC not suitable for loco
      regional therapies, compensated chronic liver disease, PS 0-2). RESULTS: A total
      of 133 applications were made, of which 57 (43%) were approved and 76 (57%)
      declined. Demographics and prognostic factors were balanced between the two
      groups. This cohort had a number of adverse prognostic features: patients were
      predominantly PS 1-2; the majority had multifocal disease with the largest lesion
      being >5 cm; and macroscopic vascular invasion, metastases, and AFP >,000 ng ml(
      1), were each present in one-third of cases. The median time from application to
      funding decision was 17 days (range 3-260 days). For the primary 'intention-to
      treat' analysis, median overall survival was 4.1 months when funding was
      declined, and 9.5 months when funding was approved (hazard ratio (HR) 0.48; 95%
      CI 0.3186-0.7267; P=0.0005). CONCLUSION: These data support the use of sorafenib
      for patients with advanced HCC as an effective intervention. In the United
      Kingdom, this applies to a relatively small group of patients, estimated to total
      ~800 per year who, unfortunately, do not survive long enough to themselves lobby
      for the availability of this drug. These data provide a comparison of sorafenib
      with supportive care and demonstrate the potential detrimental impact on patient
      outcomes of rationing health-care resources on the basis of cost.

PMID- 23880825
TI  - The interaction between C35 and DeltaNp73 promotes chemo-resistance in ovarian
      cancer cells.
AB  - BACKGROUND: The purpose of this study was to characterise the oncogenic roles of
      C35, a novel protein binding partner of DeltaNp73, in ovarian cancer and to
      investigate the functional significance of C35-DeltaNp73 interaction in the
      regulation of chemo-resistance. METHODS: C35 expression was evaluated by
      quantitative real-time PCR in human ovarian cancer tissues and cell lines. The
      aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell
      proliferation, migration, soft agar and nude mouse xenograft. The significance of
      C35-DeltaNp73 interaction in chemo-resistance was evaluated by apoptosis assays
      and cell viability after cisplatin treatment. RESULTS: The expression of C35 was
      significantly enhanced in human ovarian cancer tissues. Overexpression of C35
      augmented proliferation, migration and tumourigenicity in ovarian cancer cell
      lines. C35 knockdown inhibited cell motility and cell growth. The co-expression
      of C35 and DeltaNp73 by transient or stable transfection in ovarian cancer cells
      induced greater resistance to cisplatin treatment than did transfection with C35
      or DeltaNp73 alone. The cisplatin resistance was demonstrated to be caused by
      increased AKT and NFkappaB activity induced by C35-DeltaNp73. CONCLUSION: Our
      results suggest that DeltaNp73 might cooperate with C35 to promote tumour
      progression and contribute to cisplatin resistance in ovarian cancer cells.
      Future studies of the functional roles of DeltaNp73 and C35 will provide insight
      that will aid in the establishment of new strategies and more effective
      therapies.

PMID- 23880826
TI  - Randomised pilot study of dose escalation using conformal radiotherapy in
      prostate cancer: long-term follow-up.
AB  - BACKGROUND: Radical three-dimensional conformal radiotherapy (CFRT) with initial
      androgen suppression (AS) is a standard management for localised prostate cancer
      (PC). This pilot study evaluated the role of dose escalation and appropriate
      target volume margin. Here, we report long-term follow-up. METHODS: Eligible
      patients had T1b-T3b N0 M0 PC. After neoadjuvant AS, they were randomised to
      CFRT, giving (a) 64 Gy with either a 1.0- or 1.5-cm margin and (b) +/-10 Gy boost
      to the prostate alone. RESULTS: One hundred and twenty-six men were randomised
      and treated. Median follow-up was 13.7 years. The median age was 66.6 years at
      randomisation. Median presenting prostate-specific antigen (PSA) was 14 ng ml(
      1). Sixty-four out of 126 patients developed PSA failure. Forty-nine out of 126
      patients restarted AS, 34 out of 126 developed metastases and 28 out of 126
      developed castrate-resistant prostate cancer (CRPC). Fifty-one out of 126
      patients died; 19 out of 51 died of PC. Median overall survival (OS) was 14.4
      years. Although escalated dose results were favourable, no statistically
      significant differences were seen between the randomised groups; PSA control
      (hazard ratio (HR): 0.77 (95% confidence interval (CI): 0.47-1.26)), development
      of CRPC (HR: 0.81 (95% CI: 0.40-1.65)), PC-specific survival (HR: 0.59 (95%
      CI:0.23-1.49)) and OS (HR: 0.81 (95% CI: 0.47-1.40)). There was no evidence of a
      difference in PSA control according to margin size (HR: 1.01 (95% CI: 0.61
      1.66)). INTERPRETATION: Long-term follow-up of this small pilot study is
      compatible with a benefit from dose escalation, but confirmation from larger
      trials is required. There was no obvious detriment using the smaller radiotherapy
      margin.

PMID- 23880828
TI  - Longitudinal patterns of psychological distress in adult survivors of childhood
      cancer.
AB  - BACKGROUND: This study investigated longitudinal patterns of psychological
      distress in adult survivors of childhood cancer. METHODS: Participants included
      4569 adult survivors in the Childhood Cancer Survivor Study Cohort (CCSS) who
      completed the Brief Symptom Inventory-18 on three occasions between 1994 and
      2010. Longitudinal latent class analysis was used to identify discrete classes of
      psychological distress. Predictors of class membership were examined through
      logistic regression modelling with odds ratios (ORs) and 95% confidence intervals
      (CIs) reported. RESULTS: Survivors were a median of 39 years of age and 30 years
      from diagnosis at the most recent follow-up. Most survivors reported few or no
      symptoms of distress over time, although subsets of survivors reported
      persistently elevated (depression: 8.9%; anxiety: 4.8%; somatisation: 7.2%) or
      significant increases in distress symptoms over the follow-up period (depression:
      10.2%; anxiety: 11.8%; somatisation: 13.0%). Increasing distress symptoms were
      predicted by survivor perception of worsening physical health over time
      (depression: OR=3.3; 95% CI=2.4-4.5; anxiety: OR=3.0; 95% CI=2.2-4.0;
      somatisation: OR=5.3; 95% CI=3.9-7.4). Persistent distress symptoms were also
      predicted by survivor perception of worsening physical health over time, as well
      as by worsening pain and ending analgesic use. CONCLUSION: Subgroups of adult
      survivors are at-risk for chronic distress or significant increases in distress
      decades following their original cancer diagnosis. Routine screening of
      psychological distress in adult survivors of childhood cancer is warranted,
      especially for survivors who experience physical health morbidities.

PMID- 23880827
TI  - Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell
      survival by protecting cells from oxidative stress.
AB  - OBJECTIVE: We have previously identified peroxiredoxin-3 (PRDX-3) as a cell
      surface protein that is androgen regulated in the LNCaP prostate cancer (PCa)
      cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible
      for neutralising reactive oxygen species. EXPERIMENTAL DESIGN: PRDX-3 expression
      was examined in tissue from 32 patients using immunohistochemistry. Subcellular
      distribution was determined using confocal microscopy. PRDX-3 expression was
      determined in antiandrogen-resistant cell lines by western blotting and
      quantitative RT-PCR. The pathways of PRDX-3 overexpression and knockdown on
      apoptosis and response to oxidative stress were investigated using protein
      arrays. RESULTS: PRDX-3 is upregulated in a number of endocrine-regulated
      tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although
      the majority of PRDX-3 is localised to the mitochondria, we have confirmed that
      PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant
      LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level.
      Resistant cells also possess an upregulation of the tricarboxylic acid (TCA)
      pathway and resistance to H2O2-induced apoptosis through a failure to activate
      pro-apoptotic pathways. Knockdown of PRDX-3 restored H2O2 sensitivity.
      CONCLUSION: Our results suggest that PRDX-3 has an essential role in regulating
      oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have
      potential as a therapeutic target in castrate-independent PCa.

PMID- 23880829
TI  - Profiles of piRNA abundances at emerging or established piRNA loci are determined
      by local DNA sequences.
AB  - Piwi-interacting RNAs (piRNAs) ensure transposable element silencing in
      Drosophila, thereby preserving genome integrity across generations. Primary
      piRNAs arise from the processing of long RNA transcripts produced in the germ
      line by a limited number of telomeric and pericentromeric loci. Primary piRNAs
      bound to the Argonaute protein Aubergine then drive the production of secondary
      piRNAs through the "ping-pong" amplification mechanism that involves an interplay
      with piRNAs bound to the Argonaute protein Argonaute-3. We recently discovered
      that clusters of P-element-derived transgenes produce piRNAs and mediate
      silencing of homologous target transgenes in the female germ line. We also
      demonstrated that some clusters are able to convert other homologous inactive
      transgene clusters into piRNA-producing loci, which then transmit their acquired
      silencing capacity over generations. This paramutation phenomenon is mediated by
      maternal inheritance of piRNAs homologous to the transgenes. Here we further
      mined our piRNA sequencing data sets generated from various strains carrying
      transgenes with partial sequence homology at distinct genomic sites. This
      analysis revealed that same sequences in different genomic contexts generate
      highly similar profiles of piRNA abundances. The strong tendency of piRNAs for
      bearing a U at their 5' end has long been recognized. Our observations support
      the notion that, in addition, the relative frequencies of Drosophila piRNAs are
      locally determined by the DNA sequence of piRNA loci. 

PMID- 23880831
TI  - [Dual diagnosis and personality traits: current situation and future research
      directions].
AB  - Dual diagnosis (DD) is the co-occurrence, in the same person, of a mental
      disorder (MD) and a substance use disorder (SUD). Nowadays, the study of the
      personality with DD is realized mainly from a categorical view, focusing on the
      detection of personality disorders and not on the traits associated to DD and the
      possible differential profile compared to those patients with only MD or SUD.
      Studies analyzing personality traits of patients with DD and their possible
      differential profile are very limited. However, existing data indicates that DD
      patients show higher levels of Sensation Seeking, Impulsivity, Harm Avoidance and
      Neuroticism; and lower levels of Persistence, Self-Direction, Self-Transcendence
      and Cooperation. Therefore, DD is associated to personality characteristics that
      suggest more disruptive behaviors, fewer resources for recovering and keeping
      abstinent and worse prognosis compared to those with only one disorder. Progress
      in the characterization of personality traits in DD, taking into consideration
      the methodological aspects to be improved could allow better adaptation of the
      integrated treatment of these patients in the future. 

PMID- 23880830
TI  - Riboswitch control of induction of aminoglycoside resistance acetyl and adenyl
      transferases.
AB  - The acquisition of antibiotic resistance by human pathogens poses a significant
      threat to public health. The mechanisms that control the proliferation and
      expression of antibiotic resistance genes are not yet completely understood. The
      aminoglycosides are a historically important class of antibiotics that were
      introduced in the 1940s. Aminoglycoside resistance is conferred most commonly
      through enzymatic modification of the drug or enzymatic modification of the
      target rRNA through methylation or through the overexpression of efflux pumps. In
      our recent paper, we reported that expression of the aminoglycoside resistance
      genes encoding the aminoglycoside acetyl transferase (AAC) and aminoglycoside
      adenyl transferase (AAD) enzymes was controlled by an aminoglycoside-sensing
      riboswitch RNA. This riboswitch is embedded in the leader RNA of the aac/aad
      genes and is associated with the integron cassette system. The leader RNA can
      sense and bind specific aminoglycosides such that the binding causes a structural
      transition in the leader RNA, which leads to the induction of aminoglycoside
      antibiotic resistance. Specific aminoglycosides induce reporter gene expression
      mediated by the leader RNA. Aminoglycoside RNA binding was measured directly and,
      aminoglycoside-induced changes in RNA structure monitored by chemical probing. UV
      cross-linking and mutational analysis identified potential aminoglycoside binding
      sites on the RNA. 

PMID- 23880832
TI  - An evidence-based approach in school prevention means an everyday fight: a case
      study of the Czech Republic's experience with national quality standards and a
      national certification system.
AB  - The Czech Republic has reached the end of a 15-year-long period of the
      development of a nationwide preventive system in schools. Reflection on this
      development can offer an interesting case study that demonstrates the general
      difficulties involved in creating a national prevention policy and implementing
      the principles of an evidence-based approach. Through its historical context the
      up-to-date outputs of the latest projects are presented as "key documents"
      (quality standards, textbook, explanatory dictionary, examples of good practice
      etc.) and a national system of assessment of quality called a certification
      procedure, which has a practical impact on the grant system of the Ministry of
      Education of the Czech Republic. This context is also used to show how certain
      European networks (EUSPR, IREFREA, etc.) can be very helpful in generalizing this
      idea across Europe. All the examples of activities on the national or
      international level seem to be promising and supportive of the increasingly
      noticeable trend of using research evidence in real practice and making the whole
      field more attractive for students and young researchers.

PMID- 23880833
TI  - [Personality pathological traits and brain metabolites as predictors of non
      abstinence in addicts with personality disorders].
AB  - Differences in pathological personality traits and disturbances in brain
      metabolites between non consumers, abstinent and non abstinent consumers were
      assessed. Participants (n=113) aged between 18-45 years with personality disorder
      (PD) were diagnosed with clinical interview and scales for depression, anxiety,
      impulsivity and dimensions of personality pathology. Brain metabolites were
      analyzed with magnetic resonance spectroscopy. Data were analyzed with ANOVA and
      multiple comparisons. Abstinent and non-abstinent differentiated from non
      consumers in emotional deregulation, inhibition, and restricted expression;
      abstinent and non-abstinent differentiated from each other in self-aggression,
      dissocial behaviour, conduct disorder, stimulus seeking and intimacy problems. N
      Acetyl Aspartate and creatine values were lower between non-abstinent in
      prefrontal, anterior cingulate cortex, cerebellar vermis and superior corona
      radiata. For abstinent, choline levels were greater in cerebellar vermis and n
      acetyl aspartate were lower in dorso-lateral prefrontal and anterior cingulated
      cortex and insula. Regarding personality traits, insecure attachment, narcissism,
      lability, self-aggression and anxiety characterize consumers and abstinent, while
      suspiciousness, rejection and character hardness are found in consumers (non
      abstinent and abstinent). Compulsive traits, unplanned body impulsiveness and
      lack of control in emotional regulation predominated in non-abstinent and
      participants with co-morbidities. Detachment and inhibition predominate in
      alcohol abuse disorder and narcissistic traits in substance abuse. 

PMID- 23880834
TI  - Perception of family support in dependents of alcohol and others drugs:
      relationship with mental disorders.
AB  - The present article aimed to analyze the relationships between perception of
      family support, levels of depression, anxiety and hopelessness in alcohol or drug
      dependent patients (AOD). Participated of this study 97 patients under treatment,
      aged between 18 and 58 years, of both genders from six private institutions for
      treatment of drug dependency, located in Santos-SP/Brazil. Participants responded
      to the Inventory of Perceived Family Support-IPSF, the Beck Depression Inventory
      BDI, Beck Anxiety Inventory-BAI, Hopelessness Scale-BHS and Criteria for
      substance abuse or dependence at DSM-IV TR. Results indicated negative
      correlations between perceived family support and levels of depression, anxiety
      and hopelessness. Moreover, family support proved to be a conditional variable
      for levels of anxiety and depression. These results indicated that the perception
      of family support may be an important social support for the patient with AOD.

PMID- 23880835
TI  - [Family prevention of drug use in Europe: a critical review of EDDRA programs].
AB  - In early adolescence, family is one of the main risk/protection agent for drug
      misuse. Its influence on health habits acquisition makes family a key target for
      prevention programs. The aim is to conduct a comparative analysis of European
      family prevention programs. For this purpose, 85 programs were reviewed. Programs
      were retrieved from EMCDDA database EDDRA (Exchange on Drug Demand Reduction
      Actions). No time period was delimited; hence time span was 1998-2011. 53% of all
      programs came from 4 countries (Ireland, Germany, Portugal and Spain). 89% were
      unspecific drug prevention or health promotion programs. Providing information
      about drugs is the main objective pursued by the majority of the programs. Over
      half the programs (59.7%) report having undergone an outcome evaluation process.
      Regarding the program objectives, 70.59% do not address any of the risk factors
      proposed by the main theories in international literature. Despite the solid
      theoretical framework that supports coherent evidence about family risk factors,
      prevention programs' objectives and components have a low theoretical compliance
      rate and the level of evaluation continues to be a challenge. Some aspects of the
      EDDRA functioning are reviewed.

PMID- 23880836
TI  - [The parenting style as protective or risk factor for substance use and other
      behavior problems among Spanish adolescents].
AB  - The aim of this study was to analyze the parental socialization styles as a
      protective or a risk factor for substance use in a sample of 673 Spanish
      adolescents (51.7% were women) aged 14-17 (M = 15.49, SD = 1.06). All
      participants completed the Parental Socialization Scale (ESPA29) and a scale of
      substance use. Additionally, they also completed a scale of delinquency and
      another one of school misconduct. A multivariate (4*2*2) analysis of variance
      (MANOVA) was applied for substance use, delinquency and school misconduct with
      parenting style, sex and age. Results from this study showed that indulgent
      parenting style was a protective factor for substance use whereas authoritarian
      style was identified as a risk factor. Moreover, results from protective and risk
      parenting styles on delinquency and school misconduct were consistent with those
      obtained on substance use. These findings have important implications for the
      development of family-based substance use prevention programs among Spanish
      adolescents and other similar cultures where indulgent parenting style is
      currently displaying a beneficial impact. 

PMID- 23880837
TI  - [Drugs consumption among Intern Specialists in Jaen (Spain) and their
      relationship to clinical counseling].
AB  - There are few studies on the prevalence of alcohol, tobacco and illegal drugs
      consumption among Specialist Interns (EIR) and their counseling to the patients.
      A multicenter cross-sectional study is carried out, consisting in a self
      administered validated questionnaire to describe the consumption of the EIR of 17
      health centers in Jaen (Andalusia) (4 hospitals, 13 primary care) and their
      relationship with their counseling. 215 EIR participate with 81% of valid
      questionnaires: mean age 31.2 years (+/- 0.7), 70% women, 13% foreigners, only 6%
      nursing. Of them 78% consumed alcohol (onset age 16.8 years +/- 0.3), 81%
      occasionally and 17% weekend. The alcohol average weekly intake was 5.9 (+/- 5.8)
      UBE, especially beer and cocktails; 17% show a binge-drinking pattern (more
      frequent in men, p = .001 x 2). 19% smoke. A total of 71% smoke on a daily bases
      (mean of 8.9 +/- 1.6 cigarettes/day); the nicotine dependence is low (68%) and
      two thirds have tried to quit. Only 3% use cannabis. A fifth part of EIR does not
      usually advise against smoking use (21%), a third part does not advise against
      alcohol (34%) and almost half of them neither advises against drugs (44%) (p =
      .001 x 2). Logistic regression shows greater clinical advice from older EIR.
      Advice against drinking alcohol provided by EIR women is more frequent (OR 2.93)
      and, probably, even more in EIR that binge drink (OR 2.32). Late smoking onset is
      related to less clinical advice against illegal drugs (OR 0.76).

PMID- 23880838
TI  - School, family and adolescent smoking.
AB  - The socio-cultural environment is an important factor involved with the onset of
      smoking during adolescence. Initiation of cigarette smoking occurs almost
      exclusively during this stage. In this context we aimed to analyze the
      association of school and family factors with adolescent smoking by a cross
      sectional study of 16 secondary schools randomly selected from the Balearic
      Islands involved 3673 students and 530 teachers. The prevalence of regular
      smoking (at least one cigarette per week) was 4.8% among first year students,
      11.6% among second year students, 14.1% among third year students, 20.9% among
      fourth year students and 22% among teachers. Among first and second year
      students, there were independent associations between regular smoking and
      adolescents' perception of being allowed to smoke at home, belonging to a single
      parent family, poor relationship with parents, poor academic performance, lack of
      interest in studies and teachers' perception of smoking in the presence of
      pupils. Among third and fourth year students, there were independent associations
      between regular smoking and poor relationship with parents, adolescents'
      perception of being allowed to smoke at home, poor academic performance, lack of
      control over student misbehavior and the school attended. The school policies and
      practices affect student related health behavior regarding smoking, independent
      of individual and family factors.

PMID- 23880839
TI  - Gender differences in the prevalence of DSM-IV alcohol use disorders in
      adolescents.
AB  - Despite the availability of data about drinking frequency and patterns, the
      surveys on alcohol use among adolescents carried out in Europe tend not to
      provide information about diagnostic criteria for alcohol use disorders (AUD) or
      estimation of their prevalence. This study assesses the prevalence of AUD among a
      sample of Spanish adolescents, to identify the most prevalent symptoms, and
      explore gender differences in AUD in this population. The final sample consisted
      of 504 participants aged 15 to 18, obtained by means of random sampling from all
      the schools in the region of Asturias (Spain). The presence of alcohol abuse (AA)
      and alcohol dependence (AD) disorders was evaluated according to DSM-IV-TR
      criteria. The results showed that 12.5% of the sample met the criteria for the
      diagnosis of AUD (6.7% for alcohol abuse, AA, and 5.8% for alcohol dependence,
      AD). The most prevalent symptoms were having social problems for AA diagnosis (9%
      of students who reported alcohol use in the past year) and tolerance for AD
      diagnosis (45.8% of students who reported alcohol use in the past year). Males
      showed a significantly higher score than females in AUD, AA and two AA diagnosis
      criteria (hazardous use and legal problems). The prevalence of AUD among Spanish
      adolescents is very high, males being more likely than females to endorse
      criteria for AUD and AA, though not for AD. These findings reveal a serious
      health issue and highlight the need to develop preventive efforts and provide
      coordinated alcohol-abuse interventions. 

PMID- 23880840
TI  - [Raves and drug use from an epidemiologic and psychosocial approach: a
      bibliographic systematic review].
AB  - The high drug use that occurs at raves and the specific characteristics of these
      parties make them a high risk recreational context the health of participants.
      The aim of this paper is to establish a categorization of research on drug use
      and raves according to their objectives and main results. Knowledge and research
      needs identified as a result of this review are discussed. To this end, a
      systematic review of scientific literature through Medline, Psycinfo and Psicodoc
      was conducted. After applying the inclusion criteria, 36 papers were obtained,
      classified into six categories. The results show that 23 studies aim psychosocial
      profile analysis, and the prevalence and patterns of drug use. Nine studies focus
      on risks related to drug use, and nine in the drug effects. Given the high risk
      associated with raves and the scarcity of empirical studies identified, the need
      to develop further empirical studies is addressed. There is still insufficient
      evidence to guide intervention strategies to prevent risks and harms among
      ravers. There is also a need to explore: polydrug use, harm reduction strategies,
      positive effects and motivations. 

PMID- 23880841
TI  - High complication rate following distal biceps refixation with cortical button.
AB  - PURPOSE: There are several methods for the refixation of the distal biceps tendon
      which show a variable complication rate. The aim of the present study was to
      evaluate the clinical outcome and complication rate after distal biceps repair in
      cortical button technique. METHODS: Clinical results, complications, strength of
      elbow flexion and supination and radiological evidence of heterotopic
      ossification in patients reporting persistent pain were evaluated in 27 male
      patients after an average of 36.1 month following distal biceps tendon repair in
      cortical button technique. RESULTS: The mean Mayo elbow performance score was
      95.9 (SD 11.9), the mean disabilities of the arm, shoulder and hand score was 1.9
      (SD 4.9) and the mean American shoulder and elbow surgeons (ASES) score was 94.6
      (SD 11.6). The mean flexion and supination strength of the involved side relative
      to the uninvolved side was 91.7 % (SD 12.6) and 87.8 % (SD 15.9). Nine patients
      had 14 different complications including four transient lesions of the posterior
      interosseous nerve, two persistent lesions of the superficial branch of the
      radial nerve, one symptomatic massive heterotopic ossification and one disengaged
      cortical button. Three patients had six revisions. Patients with complications
      had a significantly lower relative supination strength, Mayo elbow performance
      score, ASES score, pain on VAS (p < 0.05 each) and satisfaction (p = 0.005).
      CONCLUSIONS: As described for other techniques there is a high complication rate
      of distal biceps tendon repair in cortical button technique which resulted in
      inferior functional results and satisfaction. Surgeons treating patients with
      distal biceps tendon rupture should know the specific complications and know how
      to avoid them. LEVEL OF EVIDENCE: Case series with no comparison group, Level IV.

PMID- 23880842
TI  - Severe posttraumatic radiocarpal cartilage damage: first report of autologous
      chondrocyte implantation.
AB  - STUDY DESIGN: Case report. CLINICAL QUESTION: Traumatic articular cartilage
      defects predispose to secondary osteoarthritis accompanied by impairment or
      complete loss of function in the corresponding joint. On this account, the timely
      and correct diagnosis as well as the selection of an appropriate therapy for
      reconstruction of articular cartilage defects is important. METHODS: A 22-year
      old healthy male patient with history of traumatic intra-articular distal radius
      fracture is presented with in the course detectable 4 degrees  cartilage damage
      in the fovea scaphoidea and into the fovea lunata. For the first time, autologous
      chondrocyte implantation by the use of an in situ polymerizable albumin
      hyaluronic acid gel was performed to restore the articular cartilage. RESULTS:
      The assessment 6 months after autologous chondrocyte implantation using the
      standard DASH questionnaire for upper extremity pointed out an improvement in the
      patient outcome (DASH score pre-operative: 10.8 and 6 months post-operative:
      7.5). The clinical examination also showed an improvement in the range of
      movement of the wrist without pain. The radiological control investigation (MRI-
      examination) of the wrist 6 months after implantation also revealed a good
      integration of the implant. CONCLUSION: The case presented here demonstrates the
      first use of autologous chondrocyte implantation for cartilage reconstruction
      using an in situ polymerizable albumin-hyaluronic acid gel after traumatic
      cartilage lesion with 4 degrees  cartilage damage of the wrist in a 22-year-old
      non-smoking, active and healthy man. Initial results are promising in terms of
      mobility, pain and patient outcome. However, further clinical studies have to be
      performed with larger number of cases.

PMID- 23880843
TI  - Distribution, sources and potential risk of HCH and DDT in soils from a typical
      alluvial plain of the Yangtze River Delta region, China.
AB  - Spatial distribution, sources and potential health risks of organochlorine
      pesticides (OCPs), including hexachlorocyclohexane (HCH) and
      dichlorodiphenyltrichloroethane (DDT), in surface soils (n = 544) collected from
      a typical alluvial plain of the Yangtze River Delta region, China, were
      elucidated. Concentrations of SigmaHCH and SigmaDDT in soils ranged from less
      than the limit of detection (<LOD) to 99.0 ng g(-1), dry weight (dw) (mean 3.23
      ng g(-1) dw) and <LOD to 600 ng g(-1) dw (mean 88.8 ng g(-1) dw), respectively.
      Historical applications of HCH and DDT were the major sources of the residue in
      soils. HCH was mainly distributed in Anthrosols in the southern part of the
      watershed, while DDT was mainly distributed in Cambosols in the northern part.
      The 95 % cumulative probability incremental lifetime cancer risks (ILCRs) of
      different age groups such as children, youths, and adults all exceeded the
      acceptable risk level of 10(-6) recommended by USEPA for carcinogenic chemicals.
      The spatial distributions of ?ILCRs were consistent with concentrations of OCPs
      in soils, while they were slight different for the different age groups. Adult
      females had the greatest risk of OCPs in soils, followed by children, while
      youths had the least risk. The ingestion of OCPs in soils was the more important
      route of exposure compared with dermal and inhalation exposures. The
      concentration of OCPs in soils, the particulate emission factor, the fraction of
      dermal exposure ratio, and the soil ingestion rate were the major contributing
      variables to total ILCRs according to sensitivity analyses.

PMID- 23880844
TI  - Gene expression analyses support fallopian tube epithelium as the cell of origin
      of epithelial ovarian cancer.
AB  - Folate receptor alpha (FOLR1/FRA) is reported to be overexpressed in epithelial
      ovarian cancers (EOC), especially the serous histotype. Further, while
      dysregulation of the folate-dependent 1-carbon cycle has been implicated in
      tumorogenesis, little is known relative to the potential mechanism of action of
      FOLR1 expression in these processes. We therefore investigated the expression of
      FOLR1, other folate receptors, and genes within the 1-carbon cycle in samples of
      EOC, normal ovary and fallopian tube on a custom TaqMan Low Density Array. Also
      included on this array were known markers of EOC such as MSLN, MUC16 and HE4.
      While few differences were observed in the expression profiles of genes in the 1
      carbon cycle, genes previously considered to be overexpressed in EOC (e.g.,
      FOLR1, MSLN, MUC16 and HE4) showed significantly increased expression when
      comparing EOC to normal ovary. However, when the comparator was changed to normal
      fallopian tube, these differences were abolished, supporting the hypothesis that
      EOC derives from fallopian fimbriae and, further, that markers previously
      considered to be upregulated or overexpressed in EOC are most likely not of
      ovarian origin, but fallopian in derivation. Our findings therefore support the
      hypothesis that the cell of origin of EOC is tubal epithelium.

PMID- 23880845
TI  - Changes in the number of double-strand DNA breaks in Chinese hamster V79 cells
      exposed to gamma-radiation with different dose rates.
AB  - A comparative investigation of the induction of double-strand DNA breaks (DSBs)
      in the Chinese hamster V79 cells by gamma-radiation at dose rates of 1, 10 and
      400 mGy/min (doses ranged from 0.36 to 4.32 Gy) was performed. The acute
      radiation exposure at a dose rate of 400 mGy/min resulted in the linear dose
      dependent increase of the gamma-H2AX foci formation. The dose-response curve for
      the acute exposure was well described by a linear function y = 1.22 + 19.7x,
      where "y" is an average number of gamma-H2AX foci per a cell and "x" is the
      absorbed dose (Gy). The dose rate reduction down to 10 mGy/min lead to a
      decreased number of gamma-H2AX foci, as well as to a change of the dose-response
      relationship. Thus, the foci number up to 1.44 Gy increased and reached the
      "plateau" area between 1.44 and 4.32 Gy. There was only a slight increase of the
      gamma-H2AX foci number (up to 7) in cells after the protracted exposure (up to 72
      h) to ionizing radiation at a dose rate of 1 mGy/min. Similar effects of the
      varying dose rates were obtained when DNA damage was assessed using the comet
      assay. In general, our results show that the reduction of the radiation dose rate
      resulted in a significant decrease of DSBs per cell per an absorbed dose.

PMID- 23880846
TI  - Death associated protein kinases: molecular structure and brain injury.
AB  - Perinatal brain damage underlies an important share of motor and
      neurodevelopmental disabilities, such as cerebral palsy, cognitive impairment,
      visual dysfunction and epilepsy. Clinical, epidemiological, and experimental
      studies have revealed that factors such as inflammation, excitotoxicity and
      oxidative stress contribute considerably to both white and grey matter injury in
      the immature brain. A member of the death associated protein kinase (DAPk)
      family, DAPk1, has been implicated in cerebral ischemic damage, whereby DAPk1
      potentiates NMDA receptor-mediated excitotoxicity through interaction with the
      NR2BR subunit. DAPk1 also mediate a range of activities from autophagy, membrane
      blebbing and DNA fragmentation ultimately leading to cell death. DAPk mRNA levels
      are particularly highly expressed in the developing brain and thus, we
      hypothesize that DAPk1 may play a role in perinatal brain injury. In addition to
      reviewing current knowledge, we present new aspects of the molecular structure of
      DAPk domains, and relate these findings to interacting partners of DAPk1, DAPk
      regulation in NMDA-induced cerebral injury and novel approaches to blocking the
      injurious effects of DAPk1.

PMID- 23880848
TI  - Sarcosine as a potential prostate cancer biomarker--a review.
AB  - Prostate cancer (CaP) is the most common type of tumour disease in men. Early
      diagnosis of cancer of the prostate is very important, because the sooner the
      cancer is detected, the better it is treated. According to that fact, there is
      great interest in the finding of new markers including amino acids, proteins or
      nucleic acids. Prostate specific antigen (PSA) is commonly used and is the most
      important biomarker of CaP. This marker can only be detected in blood and its
      sensitivity is approximately 80%. Moreover, early stages cannot be diagnosed
      using this protein. Currently, there does not exist a test for diagnosis of early
      stages of prostate cancer. This fact motivates us to find markers sensitive to
      the early stages of CaP, which are easily detected in body fluids including
      urine. A potential is therefore attributed to the non-protein amino acid
      sarcosine, which is generated by glycine-N-methyltransferase in its biochemical
      cycle. In this review, we summarize analytical methods for quantification of
      sarcosine as a CaP marker. Moreover, pathways of the connection of synthesis of
      sarcosine and CaP development are discussed.

PMID- 23880847
TI  - (Healthy) ageing: focus on iodothyronines.
AB  - The activity of the thyroid gland diminishes during ageing, but a certain tissue
      reserve of T3 and its metabolites is maintained. This reserve is thought to play
      a regulatory role in energy homeostasis during ageing. This review critically
      assesses this notion. T3 was thought to act predominantly through pathways that
      require transcriptional regulation by thyroid hormone receptors (TRs). However,
      in recent years, it has emerged that T3 and its metabolites can also act through
      non-genomic mechanisms, including cytosolic signaling. Interestingly, differences
      may exist in the non-genomic pathways utilized by thyroid hormone metabolites and
      T3. For instance, one particular thyroid hormone metabolite, namely 3,5-diiodo-L
      thyronine (T2), increases the activity of the redox-sensitive protein deacetylase
      SIRT1, which has been associated with improvements in healthy ageing, whereas
      evidence exists that T3 may have the opposite effect. Findings suggesting that
      T3, T2, and their signaling pathways, such as those involving SIRT1 and AMP
      activated protein kinase (AMPK), are associated with improvements in diet-induced
      obesity and insulin resistance emphasize the potential importance of the thyroid
      during ageing and in ageing-associated metabolic diseases.

PMID- 23880849
TI  - The efficacy of edaravone (radicut), a free radical scavenger, for cardiovascular
      disease.
AB  - Edaravone was originally developed as a potent free radical scavenger, and has
      been widely used to treat acute ischemic stroke in Japan since 2001. Free
      radicals play an important role in the pathogenesis of a variety of diseases,
      such as cardiovascular diseases and stroke. Therefore, free radicals may be
      targets for therapeutic intervention in these diseases. Edaravone shows
      protective effects on ischemic insults and inflammation in the heart, vessel, and
      brain in experimental studies. As well as scavenging free radicals, edaravone has
      anti-apoptotic, anti-necrotic, and anti-cytokine effects in cardiovascular
      diseases and stroke. Edaravone has preventive effects on myocardial injury
      following ischemia and reperfusion in patients with acute myocardial infarction.
      Edaravone may represent a new therapeutic intervention for endothelial
      dysfunction in the setting of atherosclerosis, heart failure, diabetes, or
      hypertension, because these diseases result from oxidative stress and/or cytokine
      induced apoptosis. This review evaluates the potential of edaravone for treatment
      of cardiovascular disease, and covers clinical and experimental studies conducted
      between 1984 and 2013. We propose that edaravone, which scavenges free radicals,
      may offer a novel option for treatment of cardiovascular diseases. However,
      additional clinical studies are necessary to verify the efficacy of edaravone.

PMID- 23880851
TI  - Recent progress in pharmaceutical therapies for castration-resistant prostate
      cancer.
AB  - Since 2010, six drugs have been approved for the treatment of castration
      resistant prostate cancer, i.e., CYP17 inhibitor Abiraterone, androgen receptor
      antagonist Enzalutamide, cytotoxic agent Cabazitaxel, vaccine Sipuleucel-T,
      antibody Denosumab against receptor activator of nuclear factor kappa B ligand
      and radiopharmaceutical Alpharadin. All these drugs demonstrate improvement on
      overall survival, expect for Denosumab, which increases the bone mineral density
      of patients under androgen deprivation therapy and prolongs bone-metastasis-free
      survival. Besides further CYP17 inhibitors (Orteronel, Galeterone, VT-464 and
      CFG920), androgen receptor antagonists (ARN-509, ODM-201, AZD-3514 and EZN-4176)
      and vaccine Prostvac, more drug candidates with various mechanisms or new
      indications of launched drugs are currently under evaluation in different stages
      of clinical trials, including various kinase inhibitors and platinum complexes.
      Some novel strategies have also been proposed aimed at further potentiation of
      antitumor effects or reduction of side effects and complications related to
      treatments. Under these flourishing circumstances, more investigations should be
      performed on the optimal combination or the sequence of treatments needed to
      delay or reverse possible resistance and thus maximize the clinical benefits for
      the patients.

PMID- 23880850
TI  - Role of cytokine signaling during nervous system development.
AB  - Cytokines are signaling proteins that were first characterized as components of
      the immune response, but have been found to have pleiotropic effects in diverse
      aspects of body function in health and disease. They are secreted by numerous
      cells and are used extensively in intercellular communications to produce
      different activities, including intricate processes engaged in the ontogenetic
      development of the brain. This review discusses factors involved in brain growth
      regulation and recent findings exploring cytokine signaling pathways during
      development of the central nervous system. In view of existing data suggesting
      roles for neurotropic cytokines in promoting brain growth and repair, these
      molecules and their signaling pathways might become targets for therapeutic
      intervention in neurodegenerative processes due to diseases, toxicity, or trauma.

PMID- 23880852
TI  - Hedgehog signaling in prostate cancer and its therapeutic implication.
AB  - Activation of Hedgehog (Hh) signaling is implicated in the development and
      progression of several tumor types, including prostate cancer, which is still the
      most common non-skin malignancy and the third leading cause of cancer-related
      mortality in men in industrialized countries worldwide. Several studies have
      indicated that the Hh pathway plays a crucial role in the development as well as
      in the progression of this disease to more aggressive and even therapy-resistant
      disease states. Moreover, preclinical data have shown that inhibition of Hh
      signaling has the potential to reduce prostate cancer invasiveness and metastatic
      potential. Clinical trials investigating the benefit of Hh inhibitors in patients
      with prostate cancer have recently been initiated. However, acquired drug
      resistance has already been observed in other tumor types after long-term Hh
      inhibition. Therefore, combining Hh inhibitors with ionizing radiation,
      chemotherapy or other molecular targeted agents could represent an alternative
      therapeutic strategy. In this review, we will highlight the role of Hh signaling
      in the development and progression of prostate cancer and summarize the different
      therapeutic applications of Hedgehog inhibition.

PMID- 23880853
TI  - Toll-like receptors in atherosclerosis.
AB  - Atherosclerosis, the leading cause of cardiovascular disease (CVD), is driven by
      inflammation. Increasing evidence suggests that toll-like receptors (TLRs) are
      key orchestrators of the atherosclerotic disease process. Interestingly, a
      distinct picture is being revealed for individual receptors in atherosclerosis.
      TLRs exhibit a complex nature enabling the detection of multiple motifs named
      danger-associated molecular patterns (DAMPs) and pathogen-associated molecular
      patterns (PAMPs). Activation of these receptors triggers an intracellular
      signalling cascade mediated through MyD88 or TRIF, leading to the production of
      pro- and anti-inflammatory cytokines. In this review we explore key novel
      findings pertaining to TLR signalling in atherosclerosis, including recently
      described endosomal TLRs and future directions in TLR research.

PMID- 23880855
TI  - Effects of ospemifene on drug metabolism mediated by cytochrome P450 enzymes in
      humans in vitro and in vivo.
AB  - The objective of these investigations was to determine the possible effects of
      the novel selective estrogen receptor modulator, ospemifene, on cytochrome P450
      (CYP)-mediated drug metabolism. Ospemifene underwent testing for possible effects
      on CYP enzyme activity in human liver microsomes and in isolated human
      hepatocytes. Based on the results obtained in vitro, three Phase 1 crossover
      pharmacokinetic studies were conducted in healthy postmenopausal women to assess
      the in vivo effects of ospemifene on CYP-mediated drug metabolism. Ospemifene and
      its main metabolites 4-hydroxyospemifene and 4'-hydroxyospemifene weakly
      inhibited a number of CYPs (CYP2B6, CYP2C9, CYP2C19, CYP2C8, and CYP2D6) in
      vitro. However, only CYP2C9 activity was inhibited by 4-hydroxyospemifene at
      clinically relevant concentrations. Induction of CYPs by ospemifene in cultured
      human hepatocytes was 2.4-fold or less. The in vivo studies showed that
      ospemifene did not have significant effects on the areas under the plasma
      concentration-time curves of the tested CYP substrates warfarin (CYP2C9),
      bupropion (CYP2B6) and omeprazole (CYP2C19), demonstrating that pretreatment with
      ospemifene did not alter their metabolism. Therefore, the risk that ospemifene
      will affect the pharmacokinetics of drugs that are substrates for CYP enzymes is
      low.

PMID- 23880856
TI  - MicroRNA-27a is induced by leucine and contributes to leucine-induced
      proliferation promotion in C2C12 cells.
AB  - Leucine, a branched chain amino acid, is well known to stimulate protein
      synthesis in skeletal muscle. However, the role of leucine in myoblast
      proliferation remains unclear. In this study, we found that leucine could promote
      proliferation of C2C12 cells. Moreover, expressions of miR-27a and myostatin (a
      bona fide target of miR-27a) were upregulated and downregulated, respectively,
      following leucine treatment. We also found that miR-27a loss-of-function by
      transfection of a miR-27a inhibitor suppressed the promotion of myoblast
      proliferation caused by leucine. Our results suggest that miR-27a is induced by
      leucine and contributes to leucine-induced proliferation promotion of myoblast.

PMID- 23880854
TI  - The cellular and molecular carcinogenic effects of radon exposure: a review.
AB  - Radon-222 is a naturally occurring radioactive gas that is responsible for
      approximately half of the human annual background radiation exposure globally.
      Chronic exposure to radon and its decay products is estimated to be the second
      leading cause of lung cancer behind smoking, and links to other forms of
      neoplasms have been postulated. Ionizing radiation emitted during the radioactive
      decay of radon and its progeny can induce a variety of cytogenetic effects that
      can be biologically damaging and result in an increased risk of carcinogenesis.
      Suggested effects produced as a result of alpha particle exposure from radon
      include mutations, chromosome aberrations, generation of reactive oxygen species,
      modification of the cell cycle, up or down regulation of cytokines and the
      increased production of proteins associated with cell-cycle regulation and
      carcinogenesis. A number of potential biomarkers of exposure, including
      translocations at codon 249 of TP53 in addition to HPRT mutations, have been
      suggested although, in conclusion, the evidence for such hotspots is
      insufficient. There is also substantial evidence of bystander effects, which may
      provide complications when calculating risk estimates as a result of exposure,
      particularly at low doses where cellular responses often appear to deviate from
      the linear, no-threshold hypothesis. At low doses, effects may also be dependent
      on cellular conditions as opposed to dose. The cellular and molecular
      carcinogenic effects of radon exposure have been observed to be both numerous and
      complex and the elevated chronic exposure of man may therefore pose a significant
      public health risk that may extend beyond the association with lung
      carcinogenesis.

PMID- 23880857
TI  - Presence of proNGF-sortilin signaling complex in nigral dopamine neurons and its
      variation in relation to aging, lactacystin and 6-OHDA insults.
AB  - Growing evidence has shown that proNGF-p75NTR-sortilin signaling might be a
      crucial factor in neurodegeneration, but it remains unclear if it may function in
      nigral neurons under aging and disease. The purpose of this study is to examine
      and quantify proNGF and sortilin expression in the substantia nigra and dynamic
      changes of aging in lactacystin and 6-hydroxydopamine (6-OHDA) rat models of
      Parkinson's disease using immunofluorescence, electronic microscopy, western blot
      and FLIVO staining methods. The expression of proNGF and sortilin was abundantly
      and selectively identified in tyrosine hydroxylase (TH)-containing dopamine
      neurons in the substantia nigra. These proNGF/TH, sortilin/TH-positive neurons
      were densely distributed in the ventral tier, while they were less distributed in
      the dorsal tier, where calbindin-D28K-containing neurons were numerously located.
      A correlated decrease of proNGF, sortilin and TH was also detected during animal
      aging process. While increase of proNGF, sortilin and cleaved (active) caspase-3
      expression was found in the lactacystin model, dynamic proNGF and sortilin
      changes along with dopamine neuronal loss were demonstrated in the substantia
      nigra of both the lactacystin and 6-OHDA models. This study has thus revealed the
      presence of the proNGF-sortilin signaling complex in nigral dopamine neurons and
      its response to aging, lactacystin and 6-OHDA insults, suggesting that it might
      contribute to neuronal apoptosis or neurodegeneration during pathogenesis and
      disease progression of Parkinson's disease; the underlying mechanism and key
      signaling pathways involved warrant further investigation.

PMID- 23880858
TI  - Resveratrol inhibits ionising irradiation-induced inflammation in MSCs by
      activating SIRT1 and limiting NLRP-3 inflammasome activation.
AB  - IL-1beta, a pro-inflammatory cytokine, has been shown to contribute to radiation
      injury. Sirt1, an NAD+-dependent class III protein deacetylase, plays an
      important role in the regulation of the proinflammatory cytokines involved in
      inflammation-associated diseases. The relationship between Sirt1 and IL-1beta,
      however, has remained elusive. The present study was designed to explore the
      potential effect of Sirt1 on IL-1beta expression induced by radiation and to
      provide a new target for the development of radiation protection drugs. Our
      results showed that radiation significantly increased IL-1beta mRNA and protein
      expression and that pretreatment with resveratrol, a Sirt1 activator, inhibited
      the radiation-induced IL-1beta expression in a concentration-dependent manner,
      whereas the knockdown or inhibition of Sirt1 by nicotinamide significantly
      enhanced radiation-induced IL-1beta expression. This effect can likely be
      attributed to Sirt1-mediated inhibition of NLRP-3 inflammasome activation because
      Sirt1 inhibits the transactivation potential of NF-kappab by deacetylation, which
      then suppresses NLRP3 transcription. Taken together, the results demonstrate that
      Sirt1 exerts anti-inflammatory effects by regulating NLRP3 expression partially
      through the NF-kappab pathway in mesenchymal stem cells. More importantly, our
      findings suggest that resveratrol is an effective agent in protecting against
      radiation injury, and we provide a theoretical basis for developing a drug to
      protect against radiation injury by targeting Sirt1.

PMID- 23880859
TI  - Evaluation of the gamma-H2AX assay for radiation biodosimetry in a swine model.
AB  - There is a paucity of large animal models to study both the extent and the health
      risk of ionizing radiation exposure in humans. One promising candidate for such a
      model is the minipig. Here, we evaluate the minipig for its potential in gamma
      H2AX-based biodosimetry after exposure to ionizing radiation using both Cs137 and
      Co60 sources. gamma-H2AX foci were enumerated in blood lymphocytes and normal
      fibroblasts of human and porcine origin after ex vivo gamma-ray irradiation. DNA
      double-strand break repair kinetics in minipig blood lymphocytes and fibroblasts,
      based on the gamma-H2AX assay, were similar to those observed in their human
      counterparts. To substantiate the similarity observed between the human and
      minipig we show that minipig fibroblast radiosensitivity was similar to that
      observed with human fibroblasts. Finally, a strong gamma-H2AX induction was
      observed in blood lymphocytes following minipig total body irradiation.
      Significant responses were detected 3 days after 1.8 Gy and 1 week after 3.8 and
      5 Gy with residual gamma-H2AX foci proportional to the initial radiation doses.
      These findings show that the Gottingen minipig provides a useful in vivo model
      for validation of gamma-H2AX biodosimetry for dose assessment in humans.

PMID- 23880861
TI  - The Tumor Suppressor Roles of miR-433 and miR-127 in Gastric Cancer.
AB  - The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying
      the mechanism, diagnosis and treatment of human cancers. Currently, the
      methylation epigenetic silencing of miRNAs with tumor suppressor features by CpG
      island hypermethylation is emerging as a common hallmark of different tumors.
      Here we showed that miR-433 and miR-127 were significantly down-regulated in
      gastric cancer (GC) tissues compared with the adjacent normal regions in 86
      paired samples. Moreover, the lower level of miR-433 and miR-127 was associated
      with pM or pTNM stage in clinical gastric cancer patients. The restored
      expression of miR-433 and miR-127 in GC cells upon 5-Aza-CdR and TSA treatment
      suggested the loss of miR-433 and miR-127 was at least partly regulated by
      epigenetic modification in GC. Furthermore, the ectopic expression of miR-433 and
      miR-127 in gastric cancer cell lines HGC-27 inhibits cell proliferation, cell
      cycle progression, cell migration and invasion by directly interacting with the
      mRNA encoding oncogenic factors KRAS and MAPK4 respectively. Taken together, our
      results showed that miR-433 and miR-127 might act as tumor suppressors in GC, and
      it may provide novel diagnostic and therapeutic options for human GC clinical
      operation in the near future.

PMID- 23880860
TI  - Modulation of phytoalexin biosynthesis in engineered plants for disease
      resistance.
AB  - Phytoalexins are antimicrobial substances of low molecular weight produced by
      plants in response to infection or stress, which form part of their active
      defense mechanisms. Starting in the 1950's, research on phytoalexins has begun
      with biochemistry and bio-organic chemistry, resulting in the determination of
      their structure, their biological activity as well as mechanisms of their
      synthesis and their catabolism by microorganisms. Elucidation of the biosynthesis
      of numerous phytoalexins has permitted the use of molecular biology tools for the
      exploration of the genes encoding enzymes of their synthesis pathways and their
      regulators. Genetic manipulation of phytoalexins has been investigated to
      increase the disease resistance of plants. The first example of a disease
      resistance resulting from foreign phytoalexin expression in a novel plant has
      concerned a phytoalexin from grapevine which was transferred to tobacco.
      Transformations were then operated to investigate the potential of other
      phytoalexin biosynthetic genes to confer resistance to pathogens. Unexpectedly,
      engineering phytoalexins for disease resistance in plants seem to have been
      limited to exploiting only a few phytoalexin biosynthetic genes, especially those
      encoding stilbenes and some isoflavonoids. Research has rather focused on
      indirect approaches which allow modulation of the accumulation of phytoalexin
      employing transcriptional regulators or components of upstream regulatory
      pathways. Genetic approaches using gain- or less-of functions in phytoalexin
      engineering together with modulation of phytoalexin accumulation through
      molecular engineering of plant hormones and defense-related marker and elicitor
      genes have been reviewed.

PMID- 23880862
TI  - Disease-causing mutations in BEST1 gene are associated with altered sorting of
      bestrophin-1 protein.
AB  - Mutations in BEST1 gene, encoding the bestrophin-1 (Best1) protein are associated
      with macular dystrophies. Best1 is predominantly expressed in the retinal pigment
      epithelium (RPE), and is inserted in its basolateral membrane. We investigated
      the cellular localization in polarized MDCKII cells of disease-associated Best1
      mutant proteins to study specific sorting motifs of Best1. Real-time PCR and
      western blots for endogenous expression of BEST1 in MDCK cells were performed.
      Best1 mutant constructs were generated using site-directed mutagenesis and
      transfected in MDCK cells. For protein sorting, confocal microscopy studies,
      biotinylation assays and statistical methods for quantification of
      mislocalization were used. Analysis of endogenous expression of BEST1 in MDCK
      cells revealed the presence of BEST1 transcript but no protein. Confocal
      microscopy and quantitative analyses indicate that transfected normal human Best1
      displays a basolateral localization in MDCK cells, while cell sorting of several
      Best1 mutants (Y85H, Q96R, L100R, Y227N, Y227E) was altered. In contrast to
      constitutively active Y227E, constitutively inactive Y227F Best1 mutant localized
      basolaterally similar to the normal Best1 protein. Our data suggest that at least
      three basolateral sorting motifs might be implicated in proper Best1 basolateral
      localization. In addition, non-phosphorylated tyrosine 227 could play a role for
      basolateral delivery.

PMID- 23880863
TI  - Impacts of pr-10a overexpression at the molecular and the phenotypic level.
AB  - Biotechnological approaches using genetic modifications such as homologous gene
      overexpression can be used to decode gene functions under well-defined
      circumstances. However, only the recording of the resulting phenotypes allows
      inferences about the impact of the modification on the organisms' evolutionary,
      ecological or economic performance. We here compare a potato wild-type cell line
      with two genetically engineered cell cultures homologously overexpressing
      Pathogenesis Related Protein 10a (pr-10a). A detailed analysis of the relative
      gene-expression patterns of pr-10a and its regulators sebf and pti4 over time
      provides insights into the molecular response of heterotrophic cells to distinct
      osmotic and salt-stress conditions. Furthermore, this system serves as an
      exemplar for the tracing of respiration kinetics as a faster and more sensitive
      alternative to the laborious and time-consuming recording of growth curves. The
      utility and characteristics of the resulting data type and the requirements for
      its appropriate analysis are figured out. It is demonstrated how this novel type
      of phenotypic information together with the gene-expression-data provides
      valuable insights into the effect of genetic modifications on the behaviour of
      cells on both the molecular and the macroscopic level.

PMID- 23880864
TI  - Serum oxidant and antioxidant status following an all-out 21-km run in adolescent
      runners undergoing professional training--a one-year prospective trial.
AB  - This study investigated the 1-year longitudinal effect of professional training
      in adolescent runners on redox balance during intense endurance exercise. Changes
      in selected serum oxidant and antioxidant status in response to a 21-km running
      time trial in 10 runners (15.5 +/- 1.3 years) undergoing professional training
      were evaluated twice in 12 months (pre- and post-evaluation). Venous blood
      samples were collected immediately before and 4-h following the 21-km run for
      analysis of serum concentrations of thiobarbituric acid-reactive substances
      (TBARS), xanthine oxidase (XO), catalase (CAT), reduced glutathione (GSH),
      superoxide dismutase (SOD), and total antioxidant capacity (T-AOC). In pre
      evaluation trial, serum TBARS and SOD decreased after the 21-km run (p < 0.05)
      while XO, GSH, CAT and TAOC were unchanged. In post-evaluation trial, serum TBARS
      and SOD decreased, whereas XO and CAT increased post-exercise (p < 0.05).
      Furthermore, pre-exercise serum T-AOC, post-exercise serum XO, CAT, T-AOC (p <
      0.05), and GSH (p = 0.057) appeared to be higher than the corresponding pre
      evaluation values. The current findings suggest that a professional training
      regime in adolescent runners is not likely to jeopardize the development of their
      antioxidant defense. However, uncertainties in the maintenance of redox balance
      in runners facing increased exercise-induced oxidative stress as a consequence of
      training-induced enhancement of exercise capacity await further elucidation.

PMID- 23880866
TI  - The prevalence of depressive symptoms before and after surgery and its
      association with disability in patients undergoing lumbar spinal fusion.
AB  - PURPOSE: The aim of this study was to evaluate the prevalence of depressive
      symptoms and disability pre-operatively, at 3 months and at 1 year after lumbar
      spine fusion surgery. METHODS: Data was extracted from a dedicated lumbar spine
      fusion register, giving 232 patients (mean age 62 years, 158 females) who had
      undergone instrumented lumbar spine fusion. The frequency of depressive symptoms
      and disability was evaluated using the Depression Scale (DEPS) and Oswestry
      Disability Index (ODI). RESULTS: Depressive symptoms were found in 34, 13, and 15
      % of the patients pre-operatively, at 3 months and at 1 year after surgery,
      respectively. The mean DEPS score decreased from 16.2 to 8.6 (p < 0.001) in
      patients who had depressive symptoms pre-operatively, and from 6.1 to 3.8 (p <
      0.001) in those patients without pre-operative depressive symptoms. The mean ODI
      values pre-operatively, at 3 months and at 1 year after surgery were 53, 30, and
      23, respectively, in patients with pre-operative depressive symptoms and 41, 23,
      and 20 in those patients without pre-operative depressive symptoms. The
      differences between the groups were statistically significant at all time points
      (p < 0.001). CONCLUSIONS: One-third of our patients with chronic back pain
      undergoing spinal fusion had depressive symptoms pre-operatively. The prevalence
      of depressive symptoms decreased after surgery. Although disability remained
      higher in those patients who had reported depressive symptoms pre-operatively,
      disability did decrease significantly in both groups post-operatively. Thus,
      there is no need to exclude depressive patients from operation, but screening
      measures and appropriate treatment practises throughout both pre-operative and
      post-operative periods are encouraged.

PMID- 23880867
TI  - "Letter to the Editor" concerning the article: Adolescent idiopathic scoliosis
      treated with posteromedial translation: radiologic evaluation with a 3D low-dose
      system. Ilharreborde B, Sebag G, Skalli W, Mazda K (2013) Eur Spine J. Apr 12.
      10.1007/s00586-013-2910-6.

PMID- 23880865
TI  - Characterization of a gene encoding clathrin heavy chain in maize up-regulated by
      salicylic acid, abscisic acid and high boron supply.
AB  - Clathrin, a three-legged triskelion composed of three clathrin heavy chains
      (CHCs) and three light chains (CLCs), plays a critical role in clathrin-mediated
      endocytosis (CME) in eukaryotic cells. In this study, the genes ZmCHC1 and ZmCHC2
      encoding clathrin heavy chain in maize were cloned and characterized for the
      first time in monocots. ZmCHC1 encodes a 1693-amino acid-protein including 29
      exons and 28 introns, and ZmCHC2 encodes a 1746-amino acid-protein including 28
      exons and 27 introns. The high similarities of gene structure, protein sequences
      and 3D models among ZmCHC1, and Arabidopsis AtCHC1 and AtCHC2 suggest their
      similar functions in CME. ZmCHC1 gene is predominantly expressed in maize roots
      instead of ubiquitous expression of ZmCHC2. Consistent with a typical predicted
      salicylic acid (SA)-responsive element and four predicted ABA-responsive elements
      (ABREs) in the promoter sequence of ZmCHC1, the expression of ZmCHC1 instead of
      ZmCHC2 in maize roots is significantly up-regulated by SA or ABA, suggesting that
      ZmCHC1 gene may be involved in the SA signaling pathway in maize defense
      responses. The expressions of ZmCHC1 and ZmCHC2 genes in maize are down-regulated
      by azide or cold treatment, further revealing the energy requirement of CME and
      suggesting that CME in plants is sensitive to low temperatures.

PMID- 23880869
TI  - Answer to the letter to the editor of J.M. Duart Clemente et al. concerning
      "multilevel oblique corpectomy for cervical spondylotic myelopathy preserves
      segmental motion" by AG Chacko, M Joseph, MK Turel, K Prabhu, RT Daniel, KS Jacob
      (2012) Eur Spine J. 2012;21(7):1360-1367.

PMID- 23880868
TI  - Biomechanical comparison of vertebral augmentation with silicone and PMMA cement
      and two filling grades.
AB  - PURPOSE: Vertebral augmentation with PMMA is a widely applied treatment of
      vertebral osteoporotic compression fractures. Subsequent fractures are a common
      complication, possibly due to the relatively high stiffness of PMMA in comparison
      with bone. Silicone as an augmentation material has biomechanical properties
      closer to those of bone and might, therefore, be an alternative. The study aimed
      to investigate the biomechanical differences, especially stiffness, of vertebral
      bodies with two augmentation materials and two filling grades. METHODS: Forty
      intact human osteoporotic vertebrae (T10-L5) were studied. Wedge fractures were
      produced in a standardized manner. For treatment, PMMA and silicone at two
      filling grades (16 and 35 % vertebral body fill) were assigned to four groups.
      Each specimen received 5,000 load cycles with a high load range of 20-65 % of
      fracture force, and stiffness was measured. Additional low-load stiffness
      measurements (100-500 N) were performed for intact and augmented vertebrae and
      after cyclic loading. RESULTS: Low-load stiffness testing after cyclic loading
      normalized to intact vertebrae showed increased stiffness with 35 and 16 % PMMA
      (115 and 110 %) and reduced stiffness with 35 and 16 % silicone (87 and 82 %).
      After cyclic loading (high load range), the stiffness normalized to the untreated
      vertebrae was 361 and 304 % with 35 and 16 % PMMA, and 243 and 222 % with 35 and
      16 % silicone augmentation. For both high and low load ranges, the augmentation
      material had a significant effect on the stiffness of the augmented vertebra,
      while the filling grade did not significantly affect stiffness. CONCLUSIONS: This
      study for the first time directly compared the stiffness of silicone-augmented
      and PMMA-augmented vertebral bodies. Silicone may be a viable option in the
      treatment of osteoporotic fractures and it has the biomechanical potential to
      reduce the risk of secondary fractures.

PMID- 23880870
TI  - Successful outcomes of cochlear implantation in long-term unilateral deafness:
      brain plasticity?
AB  - To investigate the implications of duration of deafness in the rehabilitation of
      unilateral deafness utilizing cochlear implantation. From the ongoing prospective
      cochlear implantation in unilateral deafness study, we looked at five adults who
      received a cochlear implant for long-term unilateral deafness. Speech perception
      in noise and subjective evaluation of the benefits of cochlear implantation were
      measured at 3, 6, and 12 months after implantation. The results were analyzed and
      compared with published data from normal hearing individuals and adults using
      cochlear implants bilaterally. Analysis of speech perception in noise showed
      significant improvement for three spatial configurations: speech and noise from
      the front (S0/N0; P=0.003), speech from the front and noise from the normal
      hearing ear (S0/NHE; P=0.001), speech from the implanted ear, and noise from the
      normal hearing ear (SCI/NHE; P<0.001). The scores obtained at 12 months after
      surgery improved to values similar to those obtained by individuals with normal
      hearing. The results of subjective measures showed significant improvement in
      hearing over time to the scores obtained by individuals with a bilateral cochlear
      implants and those with normal hearing. In this study, older adults with more
      than 25 years of unilateral deafness obtained scores in speech perception testing
      and in subjective evaluation that are similar to those attained by individuals
      with normal hearing and/or those with bilateral cochlear implants. Therefore,
      patients with postlingual unilateral deafness should not be excluded as cochlear
      implant candidates on the basis of a long duration of deafness. 

PMID- 23880873
TI  - Novel phase change behavior of n-eicosane in nanoporous silica: emulsion template
      preparation and structure characterization using small angle X-ray scattering.
AB  - Silica microcapsules with hierarchical pore structure are prepared using a one
      step emulsion templated hydrolysis method. Silica particles of around 100 nm with
      percolated nanosized pores are self-assembled into micrometer scale spherical
      shells. The porous structure serves as an ideal host for shape stabilization of
      melted organic compounds. Small angle X-ray scattering (SAXS) results show that
      the n-eicosane encapsulated in nanoporous silica consists of mass fractal
      structure with a fractal dimension of 2.1. n-Eicosane encapsulated in the
      nanosized pores exhibits novel phase change behavior. A large melting point drop
      from 37.0 to 28.8  degrees C is observed, which is attributed to the strong
      interaction between the n-eicosane molecules and the silica skeleton. 

PMID- 23880871
TI  - Subanesthetic doses of ketamine transiently decrease serotonin transporter
      activity: a PET study in conscious monkeys.
AB  - Subanesthetic doses of ketamine, an N-methyl-D-aspartic acid (NMDA) antagonist,
      have a rapid antidepressant effect which lasts for up to 2 weeks. However, the
      neurobiological mechanism regarding this effect remains unclear. In the present
      study, the effects of subanesthetic doses of ketamine on serotonergic systems in
      conscious monkey brain were investigated. Five young monkeys underwent four
      positron emission tomography measurements with [(11)C]-3-amino-4-(2
      dimethylaminomethyl-phenylsulfanyl)benzonitrile ([(11)C]DASB) for the serotonin
      transporter (SERT), during and after intravenous infusion of vehicle or ketamine
      hydrochloride in a dose of 0.5 or 1.5 mg/kg for 40 min, and 24 h post infusion.
      Global reduction of [(11)C]DASB binding to SERT was observed during ketamine
      infusion in a dose-dependent manner, but not 24 h later. The effect of ketamine
      on the serotonin 1A receptor (5-HT1A-R) and dopamine transporter (DAT) was also
      investigated in the same subjects studied with [(11)C]DASB. No significant
      changes were observed in either 5-HT1A-R or DAT binding after ketamine infusion.
      Microdialysis analysis indicated that ketamine infusion transiently increased
      serotonin levels in the extracellular fluid of the prefrontal cortex. The present
      study demonstrates that subanesthetic ketamine selectively enhanced serotonergic
      transmission by inhibition of SERT activity. This action coexists with the rapid
      antidepressant effect of subanesthetic doses of ketamine. Further studies are
      needed to investigate whether the transient combination of SERT and NMDA
      reception inhibition enhances each other's antidepressant actions.

PMID- 23880872
TI  - N-terminal Pro-B-type natriuretic peptide and its correlation to haemodialysis
      induced myocardial stunning.
AB  - BACKGROUND: Haemodialysis (HD) is able to induce recurrent myocardial ischemia
      and segmental left-ventricular dysfunction (myocardial stunning). The association
      of N-terminal Pro-B-type natriuretic peptide (NTpro-BNP) with HD-induced
      myocardial stunning is unclear. METHODS: In 70 prevalent HD patients, HD-induced
      myocardial stunning was assessed echocardiographically at baseline and after 12
      months. The extent to which pre-dialysis NTpro-BNP was associated with the
      occurrence of HD-induced myocardial stunning was assessed as the primary
      endpoint. RESULTS: The median Ntpro-BNP concentration in this cohort was 2,154
      pg/ml (IQR 1,224-3,014). Patients experiencing HD-induced myocardial stunning at
      either time point displayed elevated NTpro-BNP values (2,418 pg/ml, IQR, 1,583
      3,474 vs. 1,751 pg/ml, IQR (536-2,029), p = 0.02). NTpro-BNP levels did not
      differ between patients showing HD-induced stunning at baseline and those
      developing stunning during the observational period (p = 0.8). NTpro-BNP levels
      drawn at the beginning of the dialysis session achieved a poor diagnostic
      accuracy for the detection of myocardial stunning (area under the ROC curve 0.61,
      95% CI 0.45-0.77), but provided an accurate rule out for myocardial stunning
      during the subsequent year (AUC 0.85, 95% CI 0.70-0.99). The calculated cut-off
      of 1,570 pg/ml achieved a sensitivity of 66% and a specificity of 78% for the
      exclusion of myocardial stunning at any time point. In logistic regression
      analysis, only low NTpro-BNP levels (OR 0.92 for every additional 100 pg/ml, 95%
      CI 0.85-0.99, p = 0.03) were significantly associated with absence of myocardial
      stunning at any time point. CONCLUSION: Predialytic NTpro-BNP levels fail to
      adequately diagnose current dialysis-induced myocardial stunning, but help to
      identify patients with a propensity to develop dialysis-induced myocardial
      stunning at any time during the next 12 months.

PMID- 23880874
TI  - A revolutionary approach facilitating co-expression of authentic human epidermal
      growth factor and basic fibroblast growth factor in both cytoplasm and culture
      medium of Escherichia coli.
AB  - During secretory or excretory production of heterologous proteins in Escherichia
      coli, peptidase processing cleaves the signal peptide off from a premature
      protein, which is then secreted as a mature product. Many proteins have been
      successfully expressed as secreted/excreted products in E. coli. However, basic
      fibroblast growth factor (bFGF), despite its suitability for secretory/excretory
      production in E. coli, has never been successfully expressed using such an
      approach. In this communication, we report the application of a revolutionary E.
      coli system to the efficient expression of not only bFGF, but also human
      epidermal growth factor (EGF) concurrently, as authentic products in the culture
      supernatant (SN). More interestingly, both polypeptides were also shown to be
      present at high levels as authentic products in the cell lysate (CL). The
      manifestation of this unusual phenomenon required a collaborative action between
      construct pWKW2, an efficient excretion vector engineered by our group to
      facilitate extracellular production of EGF, and the Sce VMA intein, which enables
      self-cleavage of protein sequences fused to it. Both bFGF and EGF derived from SN
      and CL were characterized to be bioactive. Moreover, despite employing only shake
      flask cultivation, the total yields of bFGF and EGF recovered from both SN and CL
      were impressive, amounting to 103 and 74 mg l(-1) of culture, respectively. The
      novel expression approach introduced herein may prove to be practically useful
      for the production of a wide range of proteins in the future.

PMID- 23880875
TI  - Proteolysis of abnormal prion protein with a thermostable protease from
      Thermococcus kodakarensis KOD1.
AB  - The abnormal prion protein (scrapie-associated prion protein, PrP(Sc)) is
      considered to be included in the group of infectious agents of transmissible
      spongiform encephalopathies. Since PrP(Sc) is highly resistant to normal
      sterilization procedures, the decontamination of PrP(Sc) is a significant public
      health issue. In the present study, a hyperthermostable protease, Tk-subtilisin,
      was used to degrade PrP(Sc). Although PrP(Sc) is known to be resistant toward
      proteolytic enzymes, Tk-subtilisin was able to degrade PrP(Sc) under extreme
      conditions. The level of PrP(Sc) in brain homogenates was found to decrease
      significantly in vitro following Tk-subtilisin treatment at 100  degrees C,
      whereas some protease-resistant fractions remain after proteinase K treatment.
      Rather small amounts of Tk-subtilisin (0.3 U) were required to degrade PrP(Sc) at
      100  degrees C and pH 8.0. In addition, Tk-subtilisin was observed to degrade
      PrP(Sc) in the presence of sodium dodecyl sulfate or other industrial
      surfactants. Although several proteases degrading PrP(Sc) have been reported,
      practical decontamination procedures using enzymes are not available. This report
      aims to provide basic information for the practical use of a proteolytic enzyme
      for PrP(Sc) degradation. 

PMID- 23880876
TI  - Silver-decorated orthorhombic nanotubes of lithium vanadium oxide: an impeder of
      bacterial growth and biofilm.
AB  - Reoccurrence of infectious diseases and ability of pathogens to resist
      antibacterial action has raised enormous challenges which may possibly be
      confronted by nanotechnology routes. In the present study, uniformly embedded
      silver nanoparticles in orthorhombic nanotubes of lithium vanadium oxide
      (LiV2O5/Ag) were explored as an impeder of bacterial growth and biofilm. The
      LiV2O5/Ag nanocomposites have impeded growth of Gram-positive Bacillus subtilis
      NCIM 2063 and Gram-negative Escherichia coli NCIM 2931 at 60 to 120 MUg/mL. It
      also impeded the biofilm in Pseudomonas aeruginosa NCIM 2948 at 12.5 to 25
      MUg/mL. Impedance in the growth and biofilm occurs primarily by direct action of
      the nanocomposites on the cell surfaces of test organisms as revealed by surface
      perturbation in scanning electron microscopy. As the metabolic growth and biofilm
      formation phenomena of pathogens play a central role in progression of
      pathogenesis, LiV2O5/Ag nanocomposite-based approach is likely to curb the menace
      of reoccurrence of infectious diseases. Thus, LiV2O5/Ag nanocomposites can be
      viewed as a promising candidate in biofabrication of biomedical materials. 

PMID- 23880877
TI  - 3-beta-Glucosyl-3'-beta-quinovosyl zeaxanthin, a novel carotenoid glycoside
      synthesized by Escherichia coli cells expressing the Pantoea ananatis carotenoid
      biosynthesis gene cluster.
AB  - Escherichia coli cells that express the full six carotenoid biosynthesis genes
      (crtE, crtB, crtI, crtY, crtZ, and crtX) of the bacterium Pantoea ananatis have
      been shown to biosynthesize zeaxanthin 3,3'-beta-D-diglucoside. We found that
      this recombinant E. coli also produced a novel carotenoid glycoside that
      contained a rare carbohydrate moiety, quinovose (chinovose; 6-deoxy-D-glucose),
      which was identified as 3-beta-glucosyl-3'-beta-quinovosyl zeaxanthin by
      chromatographic and spectroscopic analyses. The chirality of the aglycone of
      these zeaxanthin glycosides had been shown to be 3R,3'R, in which the hydroxyl
      groups were formed with the CrtZ enzyme. It was here demonstrated that zeaxanthin
      synthesized from beta-carotene with CrtR or CYP175A1, the other hydroxylase with
      similar catalytic function to CrtZ, possessed the same stereochemistry. It was
      also suggested that the singlet oxygen-quenching activity of zeaxanthin 3,3'-beta
      D-diglucoside, which has a chemical structure close to the new carotenoid
      glycoside, was superior to that of zeaxanthin. 

PMID- 23880878
TI  - Ruthenium(II) carbonyl complexes bearing CCC-pincer bis-(carbene) ligands:
      synthesis, structures and activities toward recycle transfer hydrogenation
      reactions.
AB  - A new series of ruthenium(II) carbonyl complexes with benzene-based CCC-pincer
      bis-(carbene) ligands, [((R)CCC(R))Ru(CO)2(X)](0/+) and
      [((R)CCC(R))Ru(CO)(NN)](+) ((R)CCC(R) = 2,6-bis-(1-alkylimidazolylidene)benzene,
      R = Me or (n)Bu; X = I, Br, CH3CN, or 6-(aminomethyl)pyridine (ampy); NN =
      2.CH3CN, or chelating ampy or bipyridine), was synthesized and fully
      characterized. X-Ray structure determinations revealed that these eight complexes
      have pseudo-octahedral configurations around the ruthenium center with the pincer
      ligand occupying three meridional sites. These complexes prove to be efficient
      precatalysts demonstrating very good activity and reusability for the transfer
      hydrogenation of ketones.

PMID- 23880879
TI  - Charge density mapping of strongly-correlated few-electron two-dimensional
      quantum dots by the scanning probe technique.
AB  - We perform a numerical simulation of the mapping of charge confined in quantum
      dots by the scanning probe technique. We solve the few-electron Schrodinger
      equation with the exact diagonalization approach and evaluate the energy maps as
      a function of the probe position. Next, from the energy maps we try to reproduce
      the charge density distribution using an integral equation given by the
      perturbation theory. The reproduced density maps are compared with the original
      ones. This study covers two-dimensional quantum dots of various geometries and
      profiles with the one-dimensional (1D) quantum dot as a limiting case. We
      concentrate on large quantum dots for which strong electron-electron correlations
      appear. For circular dots the correlations lead to the formation of Wigner
      molecules that in the presence of a tip appear in the laboratory frame. The
      unperturbed rotationally-symmetric charge density is surprisingly well reproduced
      by the mapping. We find in general that the size of the confined droplet as well
      as the spatial extent of the charge density maxima is underestimated for a
      repulsive tip potential and overestimated for an attractive tip. In lower
      symmetry quantum dots Wigner molecules with single-electron islands nucleate for
      some electron numbers even in the absence of a tip. These charge densities are
      well resolved by the mapping. These single-electron islands appear in the
      laboratory frame provided that the classical point charge density distribution is
      unique, in the 1D limit of confinement in particular. We demonstrate that for
      electron systems which possess a few equivalent classical configurations the
      repulsive probe switches between the configurations. In consequence the charge
      density evades mapping by the repulsive probe. 

PMID- 23880880
TI  - Mechanisms that lessen benefits of beta-secretase reduction in a mouse model of
      Alzheimer's disease.
AB  - The beta-secretase enzyme BACE1 (beta-site amyloid precursor protein-cleaving
      enzyme 1), which initiates amyloid-beta (Abeta) production, is an excellent
      therapeutic target for Alzheimer's disease (AD). However, recent evidence raises
      concern that BACE1-inhibiting approaches may encounter dramatic declines in their
      abilities to ameliorate AD-like pathology and memory deficits during disease
      progression. Here, we used BACE1 haploinsufficiency as a therapeutic relevant
      model to evaluate the efficacy of partial inhibition of this enzyme.
      Specifically, we crossed BACE1(+/-) mice with 5XFAD transgenic mice and
      investigated the mechanisms by which Abeta accumulation and related memory
      impairments become less sensitive to rescue by BACE1(+/-) reduction.
      Haploinsufficiency lowered BACE1 expression by ~50% in 5XFAD mice regardless of
      age in concordance with reduction in gene copy number. However, profound Abeta
      plaque pathology and memory deficits concomitant with BACE1 equivalent to wild
      type control levels remained in BACE1(+/-).5XFAD mice with advanced age (15-18
      months old). Therefore, BACE1 haploinsufficiency is not sufficient to block the
      elevation of BACE1 expression (approximately twofold), which is also reported to
      occur during human AD progression, in 5XFAD mice. Our investigation revealed that
      PERK (PKR-endoplasmic reticulum-related kinase)-dependent activation of eIF2alpha
      (eukaryotic translation initiation factor-2alpha) accounts for the persistent
      BACE1 upregulation in BACE1(+/-).5XFAD mouse brains at 15-18 months of age.
      Moreover, BACE1 haploinsufficiency was also no longer able to prevent reduction
      in the expression of neprilysin, a crucial Abeta-degrading enzyme, in 5XFAD mice
      with advanced age. These findings demonstrate that partial BACE1 suppression
      cannot attenuate deleterious BACE1-elevating or neprilysin-reducing mechanisms,
      limiting its capabilities to reduce cerebral Abeta accumulation and rescue memory
      defects during the course of AD development. 

PMID- 23880881
TI  - Mixed emotions: the contribution of alexithymia to the emotional symptoms of
      autism.
AB  - It is widely accepted that autism is associated with disordered emotion
      processing and, in particular, with deficits of emotional reciprocity such as
      impaired emotion recognition and reduced empathy. However, a close examination of
      the literature reveals wide heterogeneity within the autistic population with
      respect to emotional competence. Here we argue that, where observed, emotional
      impairments are due to alexithymia-a condition that frequently co-occurs with
      autism-rather than a feature of autism per se. Alexithymia is a condition
      characterized by a reduced ability to identify and describe one's own emotion,
      but which results in reduced empathy and an impaired ability to recognize the
      emotions of others. We briefly review studies of emotion processing in
      alexithymia, and in autism, before describing a recent series of studies directly
      testing this 'alexithymia hypothesis'. If found to be correct, the alexithymia
      hypothesis has wide-reaching implications for the study of autism, and how we
      might best support subgroups of autistic individuals with, and without,
      accompanying alexithymia. Finally, we note the presence of elevated rates of
      alexithymia, and inconsistent reports of emotional impairments, in eating
      disorders, schizophrenia, substance abuse, Parkinson's Disease, multiple
      sclerosis and anxiety disorders. We speculate that examining the contribution of
      alexithymia to the emotional symptoms of these disorders may bear fruit in the
      same way that it is starting to do in autism. 

PMID- 23880882
TI  - Functional impact of a recently identified quantitative trait locus for
      hippocampal volume with genome-wide support.
AB  - In a large brain-imaging study, a multinational consortium has recently
      identified a common genetic variation in rs7294919 being associated with
      hippocampal volume. Here, we explored whether this quantitative trait locus also
      affects hippocampal function using a previously established reliable neuroimaging
      paradigm. We observed a significant effect of rs7294919 variation in the right
      hippocampus showing that hippocampal activation increased with the number of risk
      alleles. Furthermore, the risk allele was associated with decreased performance
      in a verbal learning and memory task. By showing that this single-nucleotide
      polymorphism also relates to behavioral difference and underlying brain
      activation in memory, our findings support the idea that rs7294919 may affect the
      individual capacity to resist disease in terms of diminishing or boosting
      hippocampal resources. 

PMID- 23880883
TI  - Effects of tiotropium and salmeterol/fluticasone propionate on airway wall
      thickness in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Triple inhalation therapy with tiotropium (Tio) and
      salmeterol/fluticasone propionate combination (SFC) is widely used in the
      treatment of chronic obstructive pulmonary disease (COPD). However, the effects
      of triple therapy on airway structural changes remain unknown. OBJECTIVE: The aim
      of the study was to assess the effects of Tio, salmeterol (SM), SFC and Tio plus
      SFC on airway dimensions in COPD. METHODS: A randomized, open-label, 4-way study
      (n = 60) was conducted comparing 16-week treatment periods of Tio (18 MUg once
      daily), SM (50 MUg twice daily), SFC (50/250 MUg twice daily) and Tio (18 MUg
      once daily) plus SFC (50/250 MUg twice daily). Airway dimensions were assessed by
      a validated CT technique, and airway wall area (WA) corrected for body surface
      area (BSA), percentage WA (WA%), wall thickness/?BSA and luminal area (Ai)/BSA at
      the right apical segmental bronchus were measured. Pulmonary function and the St.
      George's Respiratory Questionnaire (SGRQ) were evaluated. RESULTS: Tio plus SFC
      resulted in a significant decrease in WA corrected for BSA and WA% compared with
      Tio, SM and SFC (p < 0.05 for all). The changes in WA% and Ai/BSA were
      significantly correlated with changes in forced expiratory volume in 1 s (r = 
      0.86, p < 0.001, and r = 0.48, p < 0.05, respectively). There were more
      significant improvements in SGRQ scores after treatment with triple therapy than
      after the 3 other treatments. CONCLUSIONS: Tio plus SFC therapy is more effective
      than Tio, SM and SFC for reducing airway wall thickness in COPD.

PMID- 23880884
TI  - Prevalence of Trichomonas vaginalis and risk factors in women treated at public
      health units in Brazil: a transversal study.
AB  - BACKGROUND: Studies have revealed high prevalence rates of Trichomonas vaginalis
      in men and women worldwide. In Brazil, where reporting is not mandatory, the true
      prevalence rate is unknown. This study determined the prevalence of the parasite
      in women attending public health units in the city of Uberlandia, Minas Gerais,
      Brazil, identifying possible risk factors for infection, and also compared three
      diagnostic techniques for detecting the parasite. METHODS: Samples of vaginal
      secretions collected from 742 women attending public health units were analyzed
      by direct wet mount examination, culture and smear test. Epidemiological
      questionnaires were administered. RESULTS: Of the total of 742 samples analyzed,
      19 (2.6%) tested positive for T. vaginalis. The variables significantly
      associated with infection were: being of black ethnicity, smoking, having
      knowledge about sexually transmitted diseases and presenting clinical signs. The
      culture method was considered the gold standard test. CONCLUSIONS: Although there
      are programs to control other sexually transmitted diseases, there are none for
      trichomoniasis. The results of this study indicate the presence of T. vaginalis
      in the female population, and points to the need for more research in Brazil to
      gain a better understanding of the profile and epidemiology of the parasite.

PMID- 23880885
TI  - Employment effects of hospital privatization in Germany.
AB  - The main argument for the ongoing privatization process is that privatization
      will lead to an increase in efficiency, which has been confirmed by a large
      number of studies. An important argument against privatization is that
      privatization may lead to employment reductions. In the hospital sector,
      potential employment reductions might also lead to a decrease in the quality of
      care. This is the first study to investigate the employment effects of different
      types of hospital privatization (i.e., for-profit vs non-profit privatization) on
      different categories of staff. A combination of propensity score matching and
      difference-in-difference methods was used to identify the causal effect. We found
      large employment reductions after for-profit privatization, while there were no
      permanent reductions after non-profit privatization. Moreover, even for-profit
      privatization does not affect all types of staff. While there are large
      reductions in non-clinical staff, we could not detect any reduction in the number
      of physicians. The consequences of the detected employment effects of
      privatization have to be addressed in greater detail in future research. 

PMID- 23880887
TI  - Oocyte morphology on day 0 correlates with aneuploidy as detected by polar body
      biopsy and FISH.
AB  - PURPOSE: For better selection of oocytes and embryos, preimplantation genetic
      screening (PGS) was introduced. As from the beginning of IVF, morphology was used
      as selection criteria; we investigated the combination of both. If there was a
      correlation between phenotype and genotype, invasive PGS might be replaced.
      METHOD: Therefore, 104 cycles with PGS were done by biopsy of the first polar
      body and FISH with five chromosomes. Morphology of the oocyte was recorded
      digitally and noted for 12 categories in 4-13 values; evaluation of the
      chromosomes was noted for five chromosomes in five values. Morphology and
      genetics were correlated to each other. RESULT: Correlations between morphology
      and genetics for day 0 were found: oocytes with an irregular or dark zona are
      less probable to have a normal chromosome 13 (80 vs. 53 %, p = 0.001). A medium
      amount of detritus in the perivitelline space makes it more probable to have a
      normal chromosome 18 (94 vs. 78 %, p = 0.001). A halo in the cytoplasm makes it
      less probable to be euploid for chromosome 22 (56 vs. 75 %, p = 0.018). For day
      1, pattern "1, 2, 3 and fine" in the pronuclei makes it more probable to be
      euploid for chromosome 22 (78 vs. 63 %, p = 0.002). CONCLUSION: There are
      correlations between the oocyte genome and its morphology also on day 0. These
      correlations are not sufficient to replace PGS.

PMID- 23880886
TI  - DENV-2 subunit proteins fused to CR2 receptor-binding domain (P28)-induces
      specific and neutralizing antibodies to the Dengue virus in mice.
AB  - Domain III (DIII) of the dengue virus (DENV) envelope (E) protein induces strong
      neutralizing type-specific antibodies. In addition, a region near the fusion loop
      in domain II (DII) induces the production of cross-reactive antibodies with
      neutralizing potential. Thus, this study aimed to generate DENV-2 recombinant
      fusion proteins (i.e., rEII*EIII and rEII*EIII/NS1*) either alone or fused to 3
      copies of P28, the minimum CR2-binding domain of the complement protein C3d. The
      4 recombinant proteins were generated in a Drosophila melanogaster Schneider 2
      (S2) cell system. The expression and secretion of the recombinant proteins were
      confirmed in vitro using immunofluorescence (IF) and western blot (WB) analyses.
      Human dengue immune serum samples recognized recombinant proteins. The
      immunogenicity of the 4 proteins in BALB/c mice was analyzed using ELISA, and the
      results revealed that the induced specific antibody response was higher in the
      groups of mice immunized with the P28 fusion proteins. Interestingly, although
      the 4 recombinant proteins were able to elicit high levels of neutralizing
      antibodies in BALB/c mice; no adjuvant effect was observed in terms of
      neutralizing antibodies in the groups immunized with proteins containing P28.
      Thus, ELISA and PRNT50 assays may evaluate different epitopes and responses,
      where ELISA showed a wider response that did not always correlate with
      neutralization. Furthermore, the elicited antibodies were able to recognize the
      immobilized E glycoprotein of DENV. All mice vaccinated with the DENV-2
      recombinant proteins showed induction of higher levels of IgG1 antibodies than of
      IgG2a antibodies. 

PMID- 23880888
TI  - Value of follicular fluid vitamin D in predicting the pregnancy rate in an IVF
      program.
AB  - PURPOSE: This study investigated whether there is a correlation between levels of
      25OH-D in the follicular fluid and the serum of infertile women and the results
      of IVF and rates of pregnancy. The association between the levels of 25OH-D in
      the follicular fluid and the vitamin D repletion status was also assessed.
      METHODS: Two hundred and twenty-one infertile women participated in an IVF cycle
      from 2010 to 2011 in a prospective observational study. Serum and follicular
      fluid were collected for vitamin D analysis. Deficient, insufficient, and
      sufficient levels of vitamin D were defined as 10, 10-29, and 30-100 ng/ml,
      respectively. IVF cycle parameters and clinical pregnancy rates were also
      compared with the vitamin D level. RESULTS: The levels of vitamin D deficiency,
      insufficiency, and sufficiency were 22.6, 70.1, and 7.2%, respectively. The
      fertilization rates associated with these three levels of vitamin D were 43.17,
      53.37, and 58.77%, respectively, (P = 0.054), and the implantation rates were
      17.33, 15.26, and 18.75%, respectively, (P = 0.579). No significant correlation
      was seen between the pregnancy rate and the serum vitamin D level (P = 0.094) or
      the follicular vitamin D level (P = 0.170). The serum and follicular fluid
      vitamin D levels showed a significant correlation (P = 0.000). CONCLUSION:
      Although vitamin D is an important hormone in the human body, no correlation was
      found between the serum and follicular vitamin D level and the pregnancy rate in
      the IVF cycle.

PMID- 23880889
TI  - Effect of ethinyl estradiol-cyproterone acetate treatment on asymmetric dimethyl
      arginine levels in women with polycystic ovary syndrome.
AB  - PURPOSE: Our study was undertaken to evaluate the levels of asymmetric dimethyl
      arginine (ADMA) in a group of patients affected with polycystic ovary syndrome
      (PCOS)--under ethinyl estradiol-cyproterone acetate treatment or not--as compared
      with a group of healthy controls. METHODS: Fifty-eight women with PCOS and 45
      patients as control group were included in the study. The 58 women with PCOS were
      separated into two groups: Group A (n = 29) were treated with an oral
      contraceptive pill containing 0.035 mg of ethinyl estradiol (EE) and 2 mg of
      cyproterone acetate (CA) (Diane-35) for 6 months. Group B (n = 29) did not take
      any drug. Group C (n = 45) was healthy women as control group. Serum levels of
      ADMA, lipid and glucose metabolism parameters, hormone profile were measured on
      the sixth month of treatment. RESULTS: ADMA levels were similar in women with
      PCOS and controls, whereas ADMA levels significantly decreased after a period of
      6 months treatment with EE + CA in women with PCOS. ADMA levels and insulin
      resistance were decreased with treatment. However, patients with PCOS had
      significantly higher total cholesterol and Low-density lipoprotein cholesterol
      (LDL-C) compared to controls, treatment with EE + CA did not provide any
      improvement on lipid parameters. CONCLUSION: Serum ADMA levels and insulin
      resistance were lower in PCOS group treated with EE + CA than control group.

PMID- 23880890
TI  - Effects of amifostine on endometriosis, comparison with N-acetyl cysteine, and
      leuprolide as a new treatment alternative: a randomized controlled trial.
AB  - PURPOSE: To assess the effects of amifostine, N-acetyl cysteine (NAC), and
      leuprolide as a scavenger in a rat endometriosis model. METHODS: This is a
      prospective randomized animal study. Setting The Animal Laboratory of Medical
      University. Animals 40 rats were used for transplantation of an autologous
      fragment of endometrial tissue onto the inner surface of the abdominal wall.
      After allowing 3 weeks for growth, laparotomies were performed to check the
      implants. Then animals were randomized into four groups: Group I amifostine (200
      mg/day loading dose after 20 mg/kg/day, p.o.); Group II NAC (200 mg/day, p.o.);
      Group III leuprolide acetate 1 mg/kg single dose, sc; and Group IV (controls) no
      medication. Three weeks later, implants were evaluated morphologically. Serum and
      peritoneal TNF-alpha levels were evaluated. The transmission electron microscopic
      examination of the peritoneal samples and ovaries was also performed. RESULTS:
      Leuprolide acetate, amifostine and NAC caused significant decreases in the mean
      implant areas and significant decreases in serum and peritoneal TNF-alpha levels.
      On comparing all groups, these reductions were higher in Group II. According to
      the transmission electron microscopic findings, leuprolide seems to be protecting
      normal structure of peritoneum best when compared to the other groups.
      CONCLUSIONS: Amifostine, NAC and leuprolide caused regression of endometriosis in
      this experimental rat model by a yet unsettled mechanism.

PMID- 23880891
TI  - Real-time tissue elastography of uterine sarcoma.

PMID- 23880892
TI  - Historical and geographical parallelism between the incidence of dental caries,
      Streptococcus mutans and sugar intake.

PMID- 23880894
TI  - Occupational status and incidences of ischemic and hemorrhagic stroke in Swedish
      men: a population-based 35-year prospective follow-up study.
AB  - This study examined variations in stroke incidence across occupational classes
      over a 35-year follow-up period. We analyzed a random population-based sample of
      6,994 men aged 47-56 years at baseline without prior history of stroke.
      Standardized incidence rates, subdistribution hazard ratios (SHRs) from competing
      risk regressions and cumulative incidence were calculated, after accounting for
      risk of death attributed to causes other than stroke. A total of 1,442 strokes
      were identified over the 35-year period with crude incidences of 5.50 (ischemic)
      and 1.16 (hemorrhagic) per 1,000 person-years. In the whole group, occupational
      class was not associated with either ischemic or hemorrhagic stroke. However,
      older men (>=51 years at baseline) with unskilled manual occupations had a
      significantly lower risk of ischemic stroke than those with high officials
      (referent). No association between occupation and stroke of either type was
      detected for men younger than 51 years. There was an inverse and graded risk of
      death from causes other than stroke; men in high official positions had the
      lowest cumulative risk and unskilled manual workers had the highest risk (P <
      0.0001). The association between occupation and ischemic stroke in older men
      persisted after accounting for competing risks of death (SHR 0.62; 95 % CI 0.46
      0.84). In conclusion, low socioeconomic status was not associated with an
      increased risk of incident hemorrhagic or ischemic stroke. Older men with the
      lowest occupational status i.e. unskilled manual had a significantly lower risk
      of ischemic stroke, even after controlling for other risk factors and competing
      risks of death. 

PMID- 23880893
TI  - Traffic, asthma and genetics: combining international birth cohort data to
      examine genetics as a mediator of traffic-related air pollution's impact on
      childhood asthma.
AB  - Associations between traffic-related air pollution and incident childhood asthma
      can be strengthened by analysis of gene-environment interactions, but studies
      have typically been limited by lack of study power. We combined data from six
      birth cohorts on: asthma, eczema and allergic rhinitis to 7/8 years, and
      candidate genes. Individual-level assessment of traffic-related air pollution
      exposure was estimated using land use regression or dispersion modeling. A total
      of 11,760 children were included in the Traffic, Asthma and Genetics (TAG) Study;
      6.3 % reported physician-diagnosed asthma at school-age, 16.0 % had asthma at
      anytime during childhood, 14.1 % had allergic rhinitis at school-age, 10.0 % had
      eczema at school-age and 33.1 % were sensitized to any allergen. For GSTP1
      rs1138272, the prevalence of heterozygosity was 16 % (range amongst individual
      cohorts, 11-17 %) and homozygosity for the minor allele was 1 % (0-2 %). For
      GSTP1 rs1695, the prevalence of heterozygosity was 45 % (40-48 %) and
      homozygosity for the minor allele, 12 % (10-12 %). For TNF rs1800629, the
      prevalence of heterozygosity was 29 % (25-32 %) and homozygosity for the minor
      allele, 3 % (1-3 %). TAG comprises a rich database, the largest of its kind, for
      investigating the effect of genotype on the association between air pollution and
      childhood allergic disease. 

PMID- 23880895
TI  - Cell cycle regulation by long non-coding RNAs.
AB  - The mammalian cell cycle is precisely controlled by cyclin-dependent kinases
      (CDKs) and related pathways such as the RB and p53 pathways. Recent research on
      long non-coding RNAs (lncRNAs) indicates that many lncRNAs are involved in the
      regulation of critical cell cycle regulators such as the cyclins, CDKs, CDK
      inhibitors, pRB, and p53. These lncRNAs act as epigenetic regulators,
      transcription factor regulators, post-transcription regulators, and protein
      scaffolds. These cell cycle-regulated lncRNAs mainly control cellular levels of
      cell cycle regulators via various mechanisms, and may provide diversity and
      reliability to the general cell cycle. Interestingly, several lncRNAs are induced
      by DNA damage and participate in cell cycle arrest or induction of apoptosis as
      DNA damage responses. Therefore, deregulations of these cell cycle regulatory
      lncRNAs may be involved in tumorigenesis, and they are novel candidate molecular
      targets for cancer therapy and diagnosis. 

PMID- 23880897
TI  - Predictive value of interim 18F-FDG-PET/CT for event-free survival in patients
      with diffuse large B-cell lymphoma homogenously treated in a phase II trial with
      six cycles of R-CHOP-14 plus pegfilgrastim as first-line treatment.
AB  - OBJECTIVE: The predictive value of interim PET/computed tomography (I-PET/CT) in
      diffuse large B-cell lymphoma (DLBCL) is controversial. Our aim was to evaluate
      the predictive value of I-PET/CT for an event-free survival. PATIENTS AND
      METHODS: We analyzed patients with DLBCL included in a prospective clinical trial
      who were treated with six cycles of dose-dense R-CHOP followed by pegfilgrastim
      and who had undergone an I-PET/CT (after two cycles) and a final PET [F-PET/CT
      (60 days after the sixth cycle)]. Event was defined as nonresponse, relapse, or
      death. RESULTS: A total of 69 patients were included. Their median age was 60
      years; 54% were male, 25% had bulky disease, and 67% had an International
      Prognostic Index of 0-2. The median follow-up duration was 28.8 months. I-PET/CT
      was positive in 34 (49%) patients and F-PET/CT was positive in 12 (17.4%). The 3
      year event-free survival was 86% for patients who were I-PET/CT negative as
      against 64% for those who were I-PET/CT positive (P=0.036). The negative and
      positive predictive values, sensitivity, and specificity of I-PET/CT for an event
      were 83, 32, 65, and 56%, respectively. In a multivariate analysis including
      baseline characteristics, I-PET/CT, and F-PET/CT, F-PET/CT was the only
      significant predictor (P<0.0005). CONCLUSION: In patients with DLBCL treated with
      dose-dense R-CHOP plus pegfilgrastim, a negative I-PET/CT is highly predictive of
      a favorable outcome and a positive I-PET/CT is of limited clinical value. These
      results do not support treatment intensification after a short course of
      chemotherapy based solely on a positive I-PET/CT.

PMID- 23880898
TI  - UK audit of quantification of left-ventricular function using gated myocardial
      perfusion imaging.
AB  - PURPOSE: The aim of the study was to evaluate UK-wide interinstitutional
      reproducibility of left-ventricular functional parameters, end-systolic volume,
      end-diastolic volume and ejection fraction, obtained from gated myocardial
      perfusion imaging (GMPI) studies using technetium-99m-labelled
      radiopharmaceuticals. The study was carried out by the UK Institute of Physics
      and Engineering in Medicine Nuclear Medicine Software Quality Group. MATERIALS
      AND METHODS: Ten anonymized clinical GMPI studies, five with normal perfusion and
      five with perfusion defects, were made available in DICOM and proprietary formats
      for download and through manufacturers' representatives. Two of the studies were
      duplicated in order to assess intraoperator repeatability, giving a total of 12
      studies. Studies were made available in 8 and 16 frames/cycle. RESULTS: A total
      of 58 institutions across England, Scotland, Wales and Northern Ireland
      participated in this study using six different computer packages. Studies were
      processed at centres using their normal clinical computers and software. The
      overall mean+/-SD ejection fraction for all centres was 58.5+/-3%; the mean end
      diastolic volume was 114+/-12 ml and the mean end-systolic volume was 54+/-6 ml.
      The results were affected by the number of frames per cycle and by the
      postprocessing computer package, but not by the reconstruction filter in the
      filtered back-projection. CONCLUSION: Calculation of functional parameters from
      GMPI using technetium-99m-labelled radiopharmaceuticals is reliable and shows
      limited variability across the UK.

PMID- 23880896
TI  - Association of maternal smoking with child cotinine levels.
AB  - INTRODUCTION: Our aim was to understand the strength of association between
      parental smoking and child environmental tobacco smoke (ETS) exposure in order to
      inform the development of future tobacco control policies. ETS was measured using
      child cotinine levels below the active smoking threshold. METHODS: Participants
      were drawn from the Avon Longitudinal Study of Parents and Children and included
      3,128 participants at age 7 years and 1,868 participants at age 15 years. The
      primary outcome was cotinine levels of nonsmoking children, to investigate the
      relationship between maternal smoking and child cotinine levels. The secondary
      outcome was cotinine levels of all individuals to investigate the relationship
      between child smoking and child cotinine levels. Maternal and child smoking
      behavior was assessed by self-report questionnaire. We adjusted for several
      sociodemographic variables. RESULTS: We found an association between maternal
      smoking and child cotinine at age 7 years (mean cotinine = 1.16ng/ml serum, ratio
      of geometric means = 3.94, 95% CI = 2.86-5.42) and at age 15 years (mean cotinine
      = 0.94ng/ml serum, ratio of geometric means = 5.26, 95% CI = 3.06-9.03), after
      adjustment for potential confounders. CONCLUSIONS: The magnitude of this
      association for children whose mothers were heavy smokers was comparable with the
      quantity of half the levels of cotinine observed among children who were
      irregular (i.e., nonweekly) active smokers, and it was greater than five times
      higher than that seen in nonsmoking children whose mothers didn't smoke. This
      provides further evidence for the importance of public health interventions to
      reduce smoking exposure in the home.

PMID- 23880899
TI  - (99m)Tc-DTPA volume of distribution, half-life and glomerular filtration rate in
      normal adults.
AB  - BACKGROUND AND AIM: Assessment of volume of distribution (VD) and half-life
      (T1/2) values during glomerular filtration rate (GFR) investigations is a useful
      quality control check. The aim of this study was to derive reference data for VD
      and T1/2 and also to provide reference data for GFR from studies performed using
      Tc-diethylenetriaminepentaacetic acid (Tc-DTPA). METHODS: This was a
      retrospective study of 126 healthy potential kidney donors (age range 18-59
      years). The GFR was evaluated from Tc-DTPA plasma clearance using the 2004
      British Nuclear Medicine Society guidelines. The association between VD and body
      surface area (BSA) was assessed. T1/2 was correlated with age and GFR. The
      correlation between the Brochner-Mortensen-corrected GFR (BM-GFRCorr) and age was
      evaluated. RESULTS: The uncorrected VD value (l) was 10.1*BSA+/-40.6% (P<0.01).
      The corrected VD value (l) was 8.19*BSA+/-34.4% (P<0.01). In individuals under
      the age of 40 years, the mean T1/2 was 95.0 min+/-36.2%. In individuals aged 40
      years and above, the T1/2 increased at a rate of 0.49 min/year (P=0.04); the T1/2
      (min) was 9480*(1/BM-GFRCorr)+/-35.1% (P<0.01). In individuals younger than 40
      years of age, the correlation between BM-GFRCorr and age was not statistically
      significant (P=0.45), and the mean GFR was 108 ml/min/1.73 m+/-27.5%. In
      individuals aged 40 years and above, the BM-GFRCorr was 170-(1.55*age)
      ml/min/1.73 m+/-36.7% (P<0.001). CONCLUSION: Well-defined reference data for VD
      and T1/2 can be used for quality control checks in GFR investigations. In
      addition to these, reference data for GFR using Tc-DTPA have been defined. This
      will enhance the interpretation of adult Tc-DTPA GFR measurements.

PMID- 23880900
TI  - Starting bedtime glargine versus NPH insulin in poorly controlled type 2 diabetic
      patients with various hyperglycemia types (fasting type or postprandial type).
AB  - Our aim was to compare the effects of an intermediate acting human insulin (NPH)
      and a long-acting insulin analog, insulin glargine, in insulin naive type 2
      diabetes patients, stratified by the type of hyperglycemia (fasting or
      postprandial type). Based on different action profiles, we hypothesized that
      patients having different hyperglycemia types would react differently when
      treated with these insulins. This is a post hoc analysis of the Lanmet study
      data. The Lanmet study was a randomized, 36-week controlled insulin initiation
      study in type 2 diabetes patients. 109 subjects with baseline HbA1c >8.0% (64
      mmol/mol) completed the study. The patients were divided into two groups
      according to fasting glucose (mmol/l)/HbA1c (%) ratio. Patients with a ratio
      >=1.3 were defined as having fasting type and those with a ratio <1.3 as having
      postprandial type hyperglycemia. The main outcome measures were change in HbA1c
      and body weight, and final insulin dose. Independently of insulin type, compared
      to patients with postprandial type hyperglycemia, those with fasting type
      hyperglycemia had 2.1 kg/m(2) greater initial BMI (p = 0.044), gained 2.0 kg more
      weight (p = 0.020, adjusted for baseline BMI p = 0.035), and had 36% greater
      final insulin dose/kg (p = 0.001). With respect to hyperglycemia type, there was
      no difference between NPH and glargine in their effects on HbA1c. When starting
      bedtime insulin in type 2 diabetes patients, those with fasting type
      hyperglycemia are prone to greater weight gain. Hyperglycemia type does not help
      in identifying patients who would benefit specially from either NPH insulin or
      insulin glargine.

PMID- 23880906
TI  - Structural, spectroscopic and theoretical studies of diosmium(III,III)
      tetracarboxylates.
AB  - The preparation of Os2(TiPB)4Cl2 (1; TiPB = 2,4,6-triisopropylbenzoate) and
      Os2(TiPB)2(OAc)2Cl2 (2) by carboxylate exchange reactions with Os2(OAc)4Cl2 is
      reported. The structure of 1 has been determined by single-crystal X-ray studies,
      and shows a paddlewheel arrangement of the ligands about the triply bonded
      diosmium core. Both compounds have magnetic moments at room temperature that are
      consistent with the presence of two unpaired electrons, and their cyclic
      voltammograms show a single redox process corresponding to the Os2(5+/6+) redox
      couple. The electronic absorption spectra of 1 and 2 display an absorption at
      ~395 nm, corresponding to the pi(Cl) ->pi*(Os2) LMCT transition, as well as
      numerous weaker absorptions at lower energy. Density functional theory (DFT)
      calculations on Os2(OAc)4Cl2 at different levels of theory (B3LYP and PBE0) have
      been used to probe the electronic structure of diosmium tetracarboxylates. The
      calculations show that these compounds have a
      sigma(2)pi(4)delta(2)delta*(1)pi*(1) electronic configuration, and time-dependent
      DFT was used to help rationalize their optical properties.

PMID- 23880907
TI  - A reduction-sensitive carrier system using mesoporous silica nanospheres with
      biodegradable polyester as caps.
AB  - Mesoporous silica nanoparticles (MSN)-polymer hybrid combined with the aliphatic
      biodegradable polyester caps on the surface were first developed in order to
      manipulate the smart intracellular release of anticancer drugs. First,
      poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-PCL) was successfully
      grafted on the surface of MSN via disulfide bonds which could cleave under a
      reduction environment in tumor cells. The anticancer drug doxorubicin (DOX) was
      encapsulated into the particle pores. The in vitro drug release profile showed
      that DOX release was significantly restricted by the polymer caps at pH 7.4,
      while it was greatly accelerated upon the addition of GSH. Cytotoxicity
      evaluation showed good biocompatibility with the hybrid particles. Fast
      endocytosis and intracellular DOX release were observed by confocal laser
      scanning microscopy (CLSM). The DOX-loaded particles exhibited comparable
      antitumor activity with free DOX towards HeLa cells and showed in a time
      dependent manner. This work developed an extensive method of utilizing aliphatic
      biodegradable polyesters as polymer caps for MSN to control drug delivery. The
      paper might offer a potential option for cancer therapy. 

PMID- 23880908
TI  - The influence of a prophylactic dose of dexamethasone for postoperative nausea
      and vomiting on plasma interleukin concentrations after laparoscopic
      cholecystectomy: a randomised trial.
AB  - BACKGROUND: Little is known about the effects of small doses of dexamethasone
      used for the prophylaxis of postoperative nausea and vomiting on the innate host
      response. OBJECTIVES: We studied the influence of dexamethasone 4 mg on the
      perioperative plasma concentrations of interleukins after laparoscopic
      cholecystectomy. We hypothesised that there would be differences in pro
      inflammatory interleukin concentrations in patients who received dexamethasone.
      DESIGN: A randomised controlled study. SETTING: University hospital. PATIENTS:
      Forty-six patients undergoing laparoscopic cholecystectomy under total
      intravenous anaesthesia were allocated randomly into one of two study groups; 42
      patients completed the study. INTERVENTIONS: Patients in group 1 (dexamethasone,
      n = 22) received dexamethasone 4 mg and group 2 (n = 20) acted as controls. MAIN
      OUTCOME MEASURES: Plasma levels of tumour necrosis factor alpha and interleukins
      1beta, 6, 8, 10 and 13 were measured before anaesthesia, before surgery and 2 and
      24 h after surgery. The frequency and number of episodes of postoperative nausea
      and vomiting were recorded. RESULTS: Areas under the curve of the percentage
      variation of interleukins 6 and 8 were significantly lower in the dexamethasone
      group. There were no significant differences between groups in the areas under
      the curve for tumour necrosis factor alpha and interleukins 1beta, 10 and 13. The
      greatest variation in interleukin concentrations was 2 h postoperatively, when
      the concentration of interleukin 6 was greater in the control group, whereas the
      concentration of interleukin 10 was higher in the dexamethasone group. Twenty
      four hours after surgery, only the concentration of interleukin 6 remained
      significantly increased in both groups (P = 0.001 and P = 0.002, respectively).
      There were no significant differences between groups in respect of postoperative
      nausea and vomiting. CONCLUSION: Prophylactic dexamethasone given before
      laparoscopic cholecystectomy produced a significant decrease in concentrations of
      interleukins 6 and 8. Further studies are needed to investigate the clinical
      implications of these findings.

PMID- 23880905
TI  - Gene-engineered T cells for cancer therapy.
AB  - T cells have the capacity to eradicate diseased cells, but tumours present
      considerable challenges that render T cells ineffectual. Cancer cells often make
      themselves almost 'invisible' to the immune system, and they sculpt a
      microenvironment that suppresses T cell activity, survival and migration. Genetic
      engineering of T cells can be used therapeutically to overcome these challenges.
      T cells can be taken from the blood of cancer patients and then modified with
      genes encoding receptors that recognize cancer-specific antigens. Additional
      genes can be used to enable resistance to immunosuppression, to extend survival
      and to facilitate the penetration of engineered T cells into tumours. Using
      genetic modification, highly active, self-propagating 'slayers' of cancer cells
      can be generated. 

PMID- 23880909
TI  - Association between alanine aminotransferase and intracerebral hemorrhage in East
      Asian populations.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) and chronic liver disease are
      relatively common in East Asian countries. However, the relationship between the
      two diseases is unclear. Thus, we investigated the association between serum
      alanine aminotransferase (ALT) levels and ICH risk in East Asian populations.
      METHODS: The East Asian Network for Stroke Prevention enrolled 279,982
      participants with ALT measurements from four cohort studies in Korea, Taiwan,
      Japan and mainland China. Among them, 1,324 ICH events and 493 ICH deaths were
      observed. Cox's proportional hazard regression analysis was performed in each
      cohort to estimate the hazard ratio (HR) after adjusting for age, blood pressure,
      diabetes, total cholesterol, smoking and alcohol intake. Combined HRs were then
      estimated using pooled analyses with fixed-effects models. RESULTS: The
      multivariate-adjusted pooled HRs (with 95% confidence interval, CI) for ICH
      incidence per 10 IU/l increments of ALT were 1.04 (1.03-1.04) in men and 1.01
      (0.98-1.04) in women. Corresponding HRs for ICH mortality were 1.04 (1.02-1.05)
      in men and 1.04 (1.00-1.08) in women. The pooled HRs for ICH incidence in
      participants with ALT levels greater than or equal to 50 IU/l compared to those
      with levels less than 20 IU/l were 1.74 (1.41-2.16) in men and 1.60 (1.06-2.40)
      in women. The corresponding HRs for ICH mortality were 1.72 (1.21-2.44) in men
      and 1.63 (0.79-3.36) in women. CONCLUSIONS: An elevated ALT level was
      independently and significantly associated with an increased risk of ICH in East
      Asian men, but the association was less prominent in women.

PMID- 23880910
TI  - Binding energy of hydrogenic impurities in quantum dots under intense laser
      radiation.
AB  - We calculate the binding energy of on- and off-center hydrogenic impurities in a
      parabolic quantum dot subjected to an intense high-frequency laser field. An
      exactly solvable model that replaces the actual Coulomb interaction with the
      donor by a non-local separable potential is introduced for calculating the
      binding energy. The separable potential allows us to solve the problem exactly
      and all calculations are carried out analytically. The action of the laser
      irradiation results in dressed Coulomb and confinement potentials. At low laser
      intensity the binding energy is found to decrease when the impurity is shifted
      away from the origin. At high laser intensity and strong confinement the opposite
      behavior is observed. We propose a simple one-dimensional model that explains the
      observed crossover. 

PMID- 23880911
TI  - Differential arrest and adhesion of tumor cells and microbeads in the
      microvasculature.
AB  - To investigate the mechanical mechanisms behind tumor cell arrest in the
      microvasculature, we injected fluorescently labeled human breast carcinoma cells
      or similarly sized rigid beads into the systemic circulation of a rat. Their
      arrest patterns in the microvasculature of mesentery were recorded and
      quantified. We found that 93% of rigid beads were arrested either at arteriole
      capillary intersections or in capillaries. Only 3% were at the capillary
      postcapillary venule intersections and in postcapillary venules. In contrast,
      most of the flexible tumor cells were either entrapped in capillaries or arrested
      at capillary or postcapillary venule-postcapillary venule intersections and in
      postcapillary venules. Only 12% of tumor cells were arrested at the arteriole
      capillary intersections. The differential arrest and adhesion of tumor cells and
      microbeads in the microvasculature was confirmed by a chi(2) test (p < 0.001).
      These results demonstrate that mechanical trapping was responsible for almost all
      the arrest of beads and half the arrest of tumor cells. Based on the measured
      geometry and blood flow velocities at the intersections, we also performed a
      numerical simulation using commercial software (ANSYS CFX 12.01) to depict the
      detailed distribution profiles of the velocity, shear rate, and vorticity at the
      intersections where tumor cells preferred to arrest and adhere. Simulation
      results reveal the presence of localized vorticity and shear rate regions at the
      turning points of the microvessel intersections, implying that hemodynamic
      factors play an important role in tumor cell arrest in the microcirculation. Our
      study helps elucidate long-debated issues related to the dominant factors in
      early-stage tumor hematogenous metastasis.

PMID- 23880912
TI  - Health inequalities and regional specific scarcity in primary care physicians:
      ethical issues and criteria.
AB  - OBJECTIVES: A substantial body of evidence supports the beneficial health impact
      of an increase in primary care physicians for underserved populations. However,
      given that in many countries primary care physician shortages persist, what
      options are available to distribute physicians and how can these be seen from an
      ethical perspective? METHODS: A literature review was performed on the topic of
      primary care physician distribution. An ethical discussion of conceivable options
      for decision makers that applied prominent theories of ethics was held. RESULTS:
      Examples of distributing primary care physicians were categorised into five
      levels depending upon levels of incentive or coercion. When analysing these
      options through theories of ethics, contrasting, and even controversial, moral
      issues were identified. However, the different morally salient criteria
      identified are of prima facie value for decision makers. CONCLUSIONS: The
      discussion provides clear criteria for decision makers to consider when
      addressing primary care physician shortages. Yet, decision makers will still need
      to assess specific situations by these criteria to ensure that any decisions they
      make are morally justifiable.

PMID- 23880913
TI  - Nanomaterial disposal by incineration.
AB  - As nanotechnology-based products enter into widespread use, nanomaterials will
      end up in disposal waste streams that are ultimately discharged to the
      environment. One possible end-of-life scenario is incineration. This review
      attempts to ascertain the potential pathways by which nanomaterials may enter
      incinerator waste streams and the fate of these nanomaterials during the
      incineration process. Although the literature on incineration of nanomaterials is
      scarce, results from studies of their behavior at high temperature or in
      combustion environments for other applications can help predict their fate within
      an incinerator. Preliminary evidence suggests nanomaterials may catalyze the
      formation or destruction of combustion by-products. Depending on their
      composition, nanomaterials may undergo physical and chemical transformations
      within the incinerator, impacting their partitioning within the incineration
      system (e.g., bottom ash, fly ash) and the effectiveness of control technology
      for removing them. These transformations may also drastically affect nanomaterial
      transport and impacts in the environment. Current regulations on incinerator
      emissions do not specifically address nanomaterials, but limits on particle and
      metal emissions may prove somewhat effective at reducing the release of
      nanomaterials in incinerator effluent. Control technology used to meet these
      regulations, such as fabric filters, electrostatic precipitators, and wet
      electrostatic scrubbers, are expected to be at least partially effective at
      removing nanomaterials from incinerator flue gas. 

PMID- 23880914
TI  - Prediction of the solubility of zinc, copper, nickel, cadmium, and lead in metal
      contaminated soils.
AB  - Risk assessment of metal-contaminated soil depends on how precisely one can
      predict the solubility of metals in soils. Responses of plants and soil organisms
      to metal toxicity are explained by the variation in free metal ion activity in
      soil pore water. This study was undertaken to predict the free ion activity of
      Zn, Cu, Ni, Cd, and Pb in metal-contaminated soil as a function of pH, soil
      organic carbon, and extractable metal content. For this purpose, 21 surface soil
      samples (0-15 cm) were collected from agricultural lands of various locations
      receiving sewage sludge and industrial effluents for a long period. One soil
      sample was also collected from agricultural land which has been under intensive
      cropping and receiving irrigation through tube well water. Soil samples were
      varied widely in respect of physicochemical properties including metal content.
      Total Zn, Cu, Ni, Cd, and Pb in experimental soils were 2,015 +/- 3,373, 236 +/-
      286, 103 +/- 192, 29.8 +/- 6.04, and 141 +/- 270 mg kg(-1), respectively. Free
      metal ion activity, viz., pZn(2+), pCu(2+), pNi(2+), pCd(2+), and pPb(2+), as
      estimated by the Baker soil test was 9.37 +/- 1.89, 13.1 +/- 1.96, 12.8 +/- 1.89,
      11.9 +/- 2.00, and 11.6 +/- 1.52, respectively. Free metal ion activity was
      predicted by pH-dependent Freundlich equation (solubility model) as a function of
      pH, organic carbon, and extractable metal. Results indicate that solubility model
      as a function of pH, Walkley-Black carbon (WBC), and ethylenediaminetetraacetic
      acid (EDTA)-extractable metals could explain the variation in pZn(2+), pCu(2+),
      pNi(2+), pCd(2+), and pPb(2+) to the extent of 59, 56, 46, 52, and 51%,
      respectively. Predictability of the solubility model based on pH, KMnO4
      oxidizable carbon, and diethylenetriaminepentaacetic acid-extractable or CaCl2
      extractable metal was inferior compared to that based on EDTA-extractable metals
      and WBC.

PMID- 23880915
TI  - Biomass and number of fish impinged at a nuclear power plant by the Baltic Sea.
AB  - The main aim of this study was to investigate the number and biomass of impinged
      fish at Forsmark Nuclear Power Plant in Sweden, located on the coast of the
      Baltic Sea. Of particular interest was the number of impinged individuals of the
      critically endangered European eel (Anguilla anguilla) which is regularly caught
      in the cooling system. Another aim was to determine the comparability of the
      results from Forsmark and results from impingement studies in other types of
      waters. Cross-systems studies make it possible to (1) estimate fish loss at
      plants where fish is not counted, and (2) to predict changes in fish loss from
      changes in electricity production or cooling water use. In 2010, 31,300,000 fish
      with a total biomass of 62,600 kg were impinged at Forsmark. In 2011, 27,300,000
      fish weighing 38,500 kg were impinged. The maximum peak in total fish number and
      biomass occurred in spring. The most critical period for herring was in late
      summer and early autumn. Regarding eel, the largest impingement losses were
      recorded in November. The number of fish agreed with earlier established
      quantities of impinged fish in both freshwater and marine ecosystems. The study
      also estimated that 1,300 critically endangered eels could survive at Forsmark
      each year if a fish return system would be constructed to allow the passage of
      fish from the plant back to the Baltic Sea.

PMID- 23880916
TI  - Dissipation, residues, and risk assessment of spirodiclofen in citrus.
AB  - The dissipation, residues, and distribution of spirodiclofen, a new type of
      insecticide and acaricide that belongs to the class of ketoenols or tetronic
      acids, in citrus were investigated in this study. Risk assessment of sprodiclofen
      was also conducted based on those data. The open-field experiments were conducted
      in Guangdong, Fujian, and Guangxi of China. Results showed that the half-lives in
      citrus ranged from 6.5 to 13.6 days at three sites. The terminal residues of
      spirodiclofen were all below the FAO/WHO maximum residue limit of 0.5 mg/kg in
      citrus, when they were determined 14 days after final application. Distribution
      of spirodiclofen in peel and flesh was analyzed, and residues were found to be
      concentrated on peel. Risk assessment was performed by calculation of risk
      quotient, which showed that the use of spirodiclofen is comparably safe for
      humans.

PMID- 23880917
TI  - Genetic characteristics of Neisseria meningitidis serogroup B strains carried by
      adolescents living in Milan, Italy: implications for vaccine efficacy.
AB  - Before a protein vaccine is introduced into a country, it is essential to
      evaluate its potential impact and estimate its benefits and costs. The aim of
      this study was to determine the genetic characteristics of Neisseria meningitidis
      B (NmB) in the pharyngeal secretions of 1375 healthy adolescents aged 13-19 y
      living in Milan, Italy, in September 2012, and the possible protection offered by
      the two currently available NmB protein vaccines. Ninety-one subjects were Nm
      carriers (6.6%), 29 (31.9%) of whom carried the NmB capsular gene. The 29
      identified strains belonged to eight clonal complexes (CCs), the majority of
      which were in the ST-41/44/Lin.3 CC (n = 11; 37.9%). All of the identified
      strains harboured fHbp alleles representing a total of 15 sub-variants: the gene
      for NHBA protein was found in all but three of the studied strains (10.3%) with
      13 identified sub-variants. There were 15 porA sub-types, seven of which were
      identified in just one CC. The findings of this study seem to suggest that both
      of the protein vaccines proposed for the prevention of invasive disease due to
      NmB (the 4-protein and the 2-protein products) have a composition that can evoke
      a theoretically effective antibody response against the meningococcal strains
      currently carried by adolescents living in Northern Italy. The genetic
      characteristics of NmB strains can be easily evaluated by means of molecular
      methods, the results of which can provide an albeit approximate estimate of the
      degree of protection theoretically provided by the available vaccines, and the
      possible future need to change their composition. 

PMID- 23880918
TI  - Comparison of KTP, Thulium, and CO2 laser in stapedotomy using specialized
      visualization techniques: thermal effects.
AB  - High-speed thermal imaging enables visualization of heating of the vestibule
      during laser-assisted stapedotomy, comparing KTP, CO2, and Thulium laser light.
      Perforation of the stapes footplate with laser bears the risk of heating of the
      inner ear fluids. The amount of heating depends on absorption of the laser light
      and subsequent tissue ablation. The ablation of the footplate is driven by strong
      water absorption for the CO2 and Thulium laser. For the KTP laser wavelength,
      ablation is driven by carbonization of the footplate and it might penetrate deep
      into the inner ear without absorption in water. The thermal effects were
      visualized in an inner ear model, using two new techniques: (1) high-speed
      Schlieren imaging shows relative dynamic changes of temperatures up to 2 ms
      resolution in the perilymph. (2) Thermo imaging provides absolute temperature
      measurements around the footplate up to 40 ms resolution. The high-speed
      Schlieren imaging showed minimal heating using the KTP laser. Both CO2 and
      Thulium laser showed heating below the footplate. Thulium laser wavelength
      generated heating up to 0.6 mm depth. This was confirmed with thermal imaging,
      showing a rise of temperature of 4.7 (+/-3.5)  degrees C for KTP and 9.4 (+/-6.9)
      for Thulium in the area of 2 mm below the footplate. For stapedotomy, the Thulium
      and CO2 laser show more extended thermal effects compared to KTP. High-speed
      Schlieren imaging and thermal imaging are complimentary techniques to study
      lasers thermal effects in tissue. 

PMID- 23880919
TI  - Transnasal flexible esophagoscopy (TNE): an evaluation of the patient's
      experience and time management.
AB  - The aim of this study was to evaluate patient's experience when performing
      transnasal flexible endoscopy using EndoSheath Technology without sedation in an
      ENT outpatient department. Patients were seen at the laryngological clinic of the
      Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital
      Heidelberg, presenting with complaints of reflux like throat cleaning, persistent
      cough, globus sensation, heartburn, or voice problems. First, we performed
      stroboscopy. In cases where physical examination findings revealed the presence
      of LPR, we performed a transnasal flexible esophagoscopy (TNE) using sterile
      EndoSheath Technology under local anesthesia. 55 patients were investigated and
      completed a questionnaire on subjective discomfort that they felt during the
      procedure. The different steps of the examination were assessed separately.
      Complications were noted down by the surgeon. All patients underwent a complete
      examination of the upper aerodigestive tract. The time needed for preparation,
      examination and cleaning measures was recorded as well. The average preparation
      time for each examination was 24 min. No complications were observed during the
      procedure. The procedure was well tolerated by all patients and was classified on
      average as "low-grade unpleasant". In summary, TNE is a safe, quick and well
      tolerated procedure that can be performed in a regular examination room under
      local anesthesia without sedation.

PMID- 23880920
TI  - Value of ultrasound in detecting central compartment lymph node metastases in
      differentiated thyroid carcinoma.
AB  - The value of ultrasound in detecting central compartment lymph node metastasis in
      patients with well-differentiated thyroid carcinoma (WDTC) is unclear.
      Prospective patients with WDTC attending a university-affiliated tertiary medical
      center between July 2010 and June 2011 underwent neck ultrasound for detection of
      central compartment lymph node metastases prior to surgery. Central lymph node
      dissection was performed during the initial surgery regardless of ultrasound
      findings. The sensitivity and specificity of preoperative ultrasound in detecting
      central lymph node metastases were calculated according to the final
      histopathological results. Sixty-four patients met the study criteria. Twenty
      four had pathologic central compartment lymph nodes according to preoperative
      ultrasound, 20 of which were confirmed by histological examination. One patient
      was found to have pathological central lymph nodes by histology which was not
      detected by US. Sensitivity of preoperative ultrasound was 95%, specificity 90%,
      and negative and positive predictive values 97 and 83%, respectively.
      Preoperative ultrasound may serve as an accurate and important tool for deciding
      the extent of surgery in WDTC.

PMID- 23880921
TI  - Determination of the biofilm formation capacity of bacterial pathogens associated
      with otorhinolaryngologic diseases in the Malaysian population.
AB  - This study aims to assess the association between microbial composition, biofilm
      formation and chronic otorhinolaryngologic disorders in Malaysia. A total of 45
      patients with chronic rhinosinusitis, chronic tonsillitis and chronic suppurative
      otitis media and 15 asymptomatic control patients were studied. Swab samples were
      obtained from these subjects. Samples were studied by conventional
      microbiological culturing, PCR-based microbial detection and Confocal Laser
      Scanning Microscopy (CLSM). Haemophilus influenzae, Staphylococcus aureus,
      Streptococcus pneumoniae, coagulase-negative staphylococci (CoNS) and other
      Streptococcus species were detected in subjects of both patient and control
      groups. Biofilm was observed in approximately half of the smear prepared from
      swab samples obtained from subjects of the patient group. Most of these were
      polymicrobial biofilms. S. aureus biofilm was most prevalent among nasal samples
      while H. influenzae biofilm was more common among ear and throat samples. Results
      from this study supported the hypothesis that chronic otorhinolaryngologic
      diseases may be biofilm related. Due to the presence of unculturable bacteria in
      biofilms present in specimens from ear, nose and throat, the use of molecular
      methods in combination with conventional microbiological culturing has
      demonstrated an improvement in the detection of bacteria from such specimens in
      this study. 

PMID- 23880922
TI  - Tumor size measured by preoperative ultrasonography and postoperative pathologic
      examination in papillary thyroid carcinoma: relative differences according to
      size, calcification and coexisting thyroiditis.
AB  - Ultrasonography (US) is a useful diagnostic modality for evaluation of the size
      and features of thyroid nodules. Tumor size is a key indicator of the surgical
      extent of thyroid cancer. We evaluated the difference in tumor sizes measured by
      preoperative US and postoperative pathologic examination in papillary thyroid
      carcinoma (PTC). We reviewed the medical records of 172 consecutive patients, who
      underwent thyroidectomy for PTC treatment. We compared tumor size, as measured by
      preoperative US, with that in postoperative specimens. And we analyzed a number
      of factors potentially influencing the size measurement, including cancer size,
      calcification and coexisting thyroiditis. The mean size of the tumor measured by
      preoperative US was 11.4, and 10.2 mm by postoperative pathologic examination.
      The mean percentage difference (US-pathology/US) of tumor sizes measured by
      preoperative US and postoperative pathologic examination was 9.9 +/- 19.3%, which
      was statistically significant (p < 0.001). When the effect of tumor size (<=10.0
      vs. 10.1-20.0 vs. >20.0 mm) and the presence of calcification or coexisting
      thyroiditis on the tumor size discrepancy between the two measurements was
      analyzed, the mean percentage differences according to tumor size (9.1 vs. 11.2%
      vs. 9.8%, p = 0.842), calcification (9.2 vs. 10.2%, p = 0.756) and coexisting
      thyroiditis (17.6 vs. 9.5%, p = 0.223) did not show statistical significance.
      Tumor sizes measured in postoperative pathology were ~90% of those measured by
      preoperative US in PTC; this was not affected by tumor size, the presence of
      calcification or coexisting thyroiditis. When the surgical extent of PTC
      treatment according to tumor size measured by US is determined, the relative
      difference between tumor sizes measured by preoperative US and postoperative
      pathologic examination should be considered.

PMID- 23880923
TI  - The use of a mandibular repositioning device for obstructive sleep apnea.
AB  - The objective of this study was to verify the effect of a mandibular
      repositioning device (MRD) on polysomnographic parameters and on the mean
      electromyographic activity of the masseter and temporal muscles in individuals
      with obstructive sleep apnea syndrome (OSAS). This is a prospective cohort study
      conducted at multidisciplinary OSAS center in a tertiary referral center.
      Nineteen individuals with mild or moderate OSAS associated with Mallampati 3-4
      were treated with an MRD during sleep. The subjects underwent diurnal
      electromyography (EM) and nocturnal polysomnography (PSG) examinations both prior
      and after initial treatment (3 months with MRD for PSG and 6 and 12 months of
      treatment for EM). The examinations performed at different times were compared.
      Comparison of the initial and final polysomnography examination revealed a
      significant mean reduction of apnea-hypopnea index (AHI) from 13.8 to 7.8. The
      successful treatment rate with the MRD was 52.6%, and the improved treatment rate
      was 68.4%. Patients with lower pre-treatment AHI presented higher rates of cure.
      There was no statistically significant change in electromyography examination
      among different times. The MRD reduced the apnea-hypopnea index in individuals
      with enlarged base of tongue and mild and moderate OSAS without damaging the
      function of the masseter and temporal muscles as determined by electromyography.

PMID- 23880924
TI  - Use of quantitative diffusion-weighted magnetic resonance imaging to predict
      human papilloma virus status in patients with oropharyngeal squamous cell
      carcinoma.
AB  - Although identification of human papilloma virus (HPV) status in oropharyngeal
      squamous cell carcinoma (OPSCC) is essential in predicting treatment response, no
      imaging modality can currently determine whether a tumor is HPV-related. In this
      retrospective study, 26 patients with OPSCC confined to the lateral wall or the
      base of tongue underwent neck magnetic resonance imaging, using T1-, T2- and
      diffusion-weighted imaging (DWI). Apparent diffusion coefficients (ADCs) in a
      region of interest covering the largest available primary tumor area of OPSCC on
      a single slice of the ADC map were calculated using two b values (0 and 1,000
      s/mm(2)). Mean and minimum ADCs were compared with HPV status, using p16
      immunohistochemistry as a surrogate marker for HPV infection. Mean and minimum
      ADCs for HPV(+) OPSCC were significantly lower than those for HPV(-) OPSCC. A cut
      off value of mean ADC for HPV(+) OPSCC of 1.027 * 10(-3) mm(2)/s yielded
      sensitivity and specificity of 83.33 and 78.57%, respectively. In conclusion, the
      present study indicates that ADC could be used to predict HPV status in patients
      with OPSCC.

PMID- 23880925
TI  - Comparative results of infratemporal fossa approach with or without facial nerve
      rerouting in jugular fossa tumors.
AB  - Jugular fossa tumors are uncommon diseases. During the surgery and due to the
      interposition of the facial nerve in the tumor approach, the facial nerve must be
      elevated from the fallopian canal and placed permanently into an anterior
      position. Although this maneuver provides a wide exposure, most of the patients
      suffer a long-term total or partial facial palsy. The purpose of this article is
      to check whether the infratemporal fossa approach without transposition of the
      facial nerve is equivalent to the approach with rerouting of the facial nerve
      regarding postsurgical morbidity. The clinical records of 52 patients who
      underwent an infratemporal fossa approach were reviewed in which 34 patients were
      segregated into two comparable groups regarding the presence or absence of
      transposition of the facial nerve. There were 19 women and 15 males. The majority
      of the patients (73%) had jugular paragangliomas. The mean follow-up of the full
      series was 66 months. It was statistically significant that the worst facial
      nerve function at hospital discharge was in the patients who underwent facial
      nerve transposition (p = 0.001). Equally the facial nerve function in the no
      rerouting group 1 year after the surgery was significantly much better than in
      the rerouting group (p = 0.003). Regarding to survival, recurrence or
      complications no significant differences were observed between both groups. Our
      study suggests that most of cases avoiding facial nerve transposition allow
      significant better functional results thereof without affecting other parameters
      such as recurrence, complications or survival.

PMID- 23880926
TI  - The Drosophila visual system: From neural circuits to behavior.
AB  - A compact genome and a tiny brain make Drosophila the prime model to understand
      the neural substrate of behavior. The neurogenetic efforts to reveal neural
      circuits underlying Drosophila vision started about half a century ago, and now
      the field is booming with sophisticated genetic tools, rich behavioral assays,
      and importantly, a greater number of scientists joining from different
      backgrounds. This review will briefly cover the structural anatomy of the
      Drosophila visual system, the animal's visual behaviors, the genes involved in
      assembling these circuits, the new and powerful techniques, and the challenges
      ahead for ultimately identifying the general principles of biological computation
      in the brain.

PMID- 23880927
TI  - pH-dependent solution structure and activity of a reduced form of the host
      defense peptide myticin C (Myt C) from the mussel Mytilus galloprovincialis.
AB  - Myticin C (Myt C) is a highly variable host-defense peptide (HDP) associated to
      the immune response in the mediterranean mussel (Mytilus galloprovincialis),
      which has shown to be active across species due to its strong antiviral activity
      against a fish rhabdovirus found in fish cells overexpressing this HDP. However,
      the potential antimicrobial properties of any synthetic analogue of Myt C has not
      yet been analysed. Thus, in this work we have synthesised the sequence of the
      mature peptide of Myt C variant c and analysed the structure activity
      relationships of its reduced (non-oxidized) form (red-MytCc). In contrast to
      results previously reported for oxidized isoforms of mussel myticins, red-MytCc
      was not active against bacteria at physiological pH and showed a moderate
      antiviral activity against the viral haemorrhagic septicaemia (VHS) rhabdovirus.
      However, its chemotactic properties remained active. Structure/function studies
      in neutral and acid environments by means of infrared spectroscopy indicated that
      the structure of red-MytCc is pH dependent, with acid media increasing its alpha
      helical content. Furthermore, red-MytCc was able to efficiently aggregate
      artificial phospholipid membranes at low pH, as well as to inhibit the
      Escherichia coli growth, suggesting that this activity is attributable to its
      more structured form in an acidic environment. All together, these results
      highlight the dynamic and environmentally sensitive behavior of red-Myt C in
      solution, and provide important insights into Myt C structure/activity
      relationships and the requirements to exert its antimicrobial/immunomodulatory
      activities. On the other hand, the pH-dependent direct antimicrobial activity of
      Myt C suggests that this HDP may be a suitable template for the development of
      antimicrobial agents that would function selectively in specific pH environments,
      which are sorely needed in this "antibiotic-resistance era". 

PMID- 23880928
TI  - Induction of apoptosis by fucoidan in human leukemia U937 cells through
      activation of p38 MAPK and modulation of Bcl-2 family.
AB  - The present study investigated possible mechanisms on the apoptosis induction of
      human leukemic cells by fucoidan, a sulfated polysaccharide found in marine
      algae. Fucoidan treatment of cells resulted in inhibition of growth and induction
      of apoptosis, as measured by 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyl-tetrazolium
      (MTT) assay, fluorescence microscopy, DNA fragmentation, and flow cytometry
      analysis. The increase in apoptosis was associated with the proteolytic
      activation of caspases, Bid cleavage, insertion of pro-apoptotic Bax into the
      mitochondria, release of cytochrome c from mitochondria to cytosol, and loss of
      mitochondria membrane potential (MMP) in U937 cells. However, apoptosis induced
      by fucoidan was attenuated by caspase inhibitors, indicating that fucoidan
      induced apoptosis was dependent on the activation of caspases. Furthermore,
      fucoidan treatment effectively activated the p38 mitogen-activated protein kinase
      (MAPK) and p38 MAPK inhibitor, SB203580, and significantly reduced fucoidan
      induced apoptosis through inhibition of Bax translocation and caspases
      activation, suggesting that the activation of p38 MAPK may play a key role in
      fucoidan-induced apoptosis. In addition, the authors found fucoidan-induced
      significantly attenuated in Bcl-2 overexpressing U937 cells, and pretreatment
      with fucoidan and HA 14-1, a small-molecule Bcl-2 inhibitor, markedly increased
      fucoidan-mediated apoptosis in Bcl-2 overexpressing U937 cells. Our findings
      imply that we may attribute some of the biological functions of p38 MAPK and Bcl
      2 to their ability to inhibit fucoidan-induced apoptosis. 

PMID- 23880929
TI  - Assessment of chemical and physico-chemical properties of cyanobacterial lipids
      for biodiesel production.
AB  - Five non-toxin producing cyanobacterial isolates from the genera Synechococcus,
      Trichormus, Microcystis, Leptolyngbya and Chlorogloea were examined in terms of
      quantity and quality as lipid feedstock for biofuel production. Under the
      conditions used in this study, the biomass productivity ranged from 3.7 to 52.7
      mg.L-1.day-1 in relation to dry biomass, while the lipid productivity varied
      between 0.8 and 14.2 mg.L-1.day-1. All cyanobacterial strains evaluated yielded
      lipids with similar fatty acid composition to those present in the seed oils
      successfully used for biodiesel synthesis. However, by combining biomass and
      lipid productivity parameters, the greatest potential was found for Synechococcus
      sp. PCC7942, M. aeruginosa NPCD-1 and Trichormus sp. CENA77. The chosen lipid
      samples were further characterized using Fourier Transform Infrared spectroscopy
      (FTIR), viscosity and thermogravimetry and used as lipid feedstock for biodiesel
      synthesis by heterogeneous catalysis. 

PMID- 23880930
TI  - Total synthesis of fellutamide B and deoxy-fellutamides B, C, and D.
AB  - The total syntheses of the marine-derived lipopeptide natural product fellutamide
      B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed
      through a novel solid-phase synthetic strategy using Weinreb amide-derived resin.
      As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric
      acid was developed utilizing a Brown allylation reaction followed by an oxidative
      cleavage-oxidation sequence as the key steps. The activity of these natural
      products, and natural product analogues was also assessed against Mycobacterium
      tuberculosis in vitro. 

PMID- 23880932
TI  - APS8, a polymeric alkylpyridinium salt blocks alpha7 nAChR and induces apoptosis
      in non-small cell lung carcinoma.
AB  - Naturally occurring 3-alkylpyridinium polymers (poly-APS) from the marine sponge
      Reniera sarai, consisting of monomers containing polar pyridinium and nonpolar
      alkyl chain moieties, have been demonstrated to exert a wide range of biological
      activities, including a selective cytotoxicity against non-small cell lung cancer
      (NSCLC) cells. APS8, an analog of poly-APS with defined alkyl chain length and
      molecular size, non-competitively inhibits alpha7 nicotinic acetylcholine
      receptors (nAChRs) at nanomolar concentrations that are too low to be
      acetylcholinesterase (AChE) inhibitory or generally cytotoxic. In the present
      study we show that APS8 inhibits NSCLC tumor cell growth and activates apoptotic
      pathways. APS8 was not toxic for normal lung fibroblasts. Furthermore, in NSCLC
      cells, APS8 reduced the adverse anti-apoptotic, proliferative effects of
      nicotine. Our results suggest that APS8 or similar compounds might be considered
      as lead compounds to develop antitumor therapeutic agents for at least certain
      types of lung cancer. 

PMID- 23880933
TI  - Proteomic investigation of the sinulariolide-treated melanoma cells A375: effects
      on the cell apoptosis through mitochondrial-related pathway and activation of
      caspase cascade.
AB  - Sinulariolide is an active compound isolated from the cultured soft coral
      Sinularia flexibilis. In this study, we investigated the effects of sinulariolide
      on A375 melanoma cell growth and protein expression. Sinulariolide suppressed the
      proliferation and migration of melanoma cells in a concentration-dependent manner
      and was found to induce both early and late apoptosis by flow cytometric
      analysis. Comparative proteomic analysis was conducted to investigate the effects
      of sinulariolide at the molecular level by comparison between the protein
      profiles of melanoma cells treated with sinulariolide and those without
      treatment. Two-dimensional gel electrophoresis (2-DE) master maps of control and
      treated A375 cells were generated by analysis with PDQuest software. Comparison
      between these maps showed up- and downregulation of 21 proteins, seven of which
      were upregulated and 14 were downregulated. The proteomics studies described here
      identify some proteins that are involved in mitochondrial dysfunction and
      apoptosis-associated proteins, including heat shock protein 60, heat shock
      protein beta-1, ubiquinol cytochrome c reductase complex core protein 1,
      isocitrate dehydrogenase (NAD) subunit alpha (down-regulated), and prohibitin (up
      regulated), in A375 melanoma cells exposed to sinulariolide. Sinulariolide
      induced apoptosis is relevant to mitochondrial-mediated apoptosis via caspase
      dependent pathways, elucidated by the loss of mitochondrial membrane potential,
      release of cytochrome c, and activation of Bax, Bad and caspase-3/-9, as well as
      suppression of p-Bad, Bcl-xL and Bcl-2. Taken together, our results show that
      sinulariolide-induced apoptosis might be related to activation of the caspase
      cascade and mitochondria dysfunction pathways. Our results suggest that
      sinulariolide merits further evaluation as a chemotherapeutic agent for human
      melanoma. 

PMID- 23880934
TI  - Occurrence of the microcystins MC-LW and MC-LF in Dutch surface waters and their
      contribution to total microcystin toxicity.
AB  - Microcystins (MCs) are the most frequently found cyanobacterial toxins in
      freshwater systems. Many MC variants have been identified and variants differ in
      their toxicity. Recent studies showed that the variants MC-LW and MC-LF might be
      more toxic than MC-LR, the variant that is most abundant and mostly used for risk
      assessments. As little is known about the presence of these two variants in The
      Netherlands, we determined their occurrence by analyzing 88 water samples and 10
      scum samples for eight MC variants ((dm-7-)MC-RR, MC-YR, (dm-7-)MC-LR, MC-LY, MC
      LW and MC-LF) by liquid chromatography with tandem mass spectrometry detection.
      All analyzed MC variants were detected, and MC-LW and/or MC-LF were present in
      32% of the MC containing water samples. When MC-LW and MC-LF were present, they
      contributed to nearly 10% of the total MC concentrations, but due to their
      suspected high toxicity, their average contribution to the total MC toxicity was
      estimated to be at least 45%. Given the frequent occurrence and possible high
      toxicity of MC-LW and MC-LF, it seems better to base health risk assessments on
      the toxicity contributions of different MC variants than on MC-LR concentrations
      alone. 

PMID- 23880931
TI  - Marine pharmacology in 2009-2011: marine compounds with antibacterial,
      antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and
      antiviral activities; affecting the immune and nervous systems, and other
      miscellaneous mechanisms of action.
AB  - The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented
      in this review, following the format used in the 1998-2008 reviews of this
      series. The pharmacology of structurally-characterized compounds isolated from
      marine animals, algae, fungi and bacteria is discussed in a comprehensive manner.
      Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral
      pharmacological activities were reported for 102 marine natural products.
      Additionally, 60 marine compounds were observed to affect the immune and nervous
      system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68
      marine metabolites were shown to interact with a variety of receptors and
      molecular targets, and thus will probably contribute to multiple pharmacological
      classes upon further mechanism of action studies. Marine pharmacology during 2009
      2011 remained a global enterprise, with researchers from 35 countries, and the
      United States, contributing to the preclinical pharmacology of 262 marine
      compounds which are part of the preclinical pharmaceutical pipeline. Continued
      pharmacological research with marine natural products will contribute to enhance
      the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine
      natural products, analogs or derivatives targeting a limited number of disease
      categories. 

PMID- 23880935
TI  - Antioxidant and anti-inflammatory activities of barettin.
AB  - In this paper, we present novel bioactivity for barettin isolated from the marine
      sponge Geodia barretti. We found that barettin showed strong antioxidant activity
      in biochemical assays as well as in a lipid peroxidation cell assay. A de
      brominated synthetic analogue of barettin did not show the same activity in the
      antioxidant cell assay, indicating that bromine is important for cellular
      activity. Barettin was also able to inhibit the secretion of the inflammatory
      cytokines IL-1beta and TNFalpha from LPS-stimulated THP-1 cells. This combination
      of anti-inflammatory and antioxidant activities could indicate that barettin has
      an atheroprotective effect and may therefore be an interesting product to prevent
      development of atherosclerosis. 

PMID- 23880936
TI  - Production, characterization, and antioxidant activity of fucoxanthin from the
      marine diatom Odontella aurita.
AB  - The production, characterization, and antioxidant capacity of the carotenoid
      fucoxanthin from the marine diatom Odontella aurita were investigated. The
      results showed that low light and nitrogen-replete culture medium enhanced the
      biosynthesis of fucoxanthin. The maximum biomass concentration of 6.36 g L-1 and
      maximum fucoxanthin concentration of 18.47 mg g-1 were obtained in cultures grown
      in a bubble column photobioreactor (O 3.0 cm inner diameter), resulting in a
      fucoxanthin volumetric productivity of 7.96 mg L-1 day-1. A slight reduction in
      biomass production was observed in the scaling up of O. aurita culture in a flat
      plate photobioreactor, yet yielded a comparable fucoxanthin volumetric
      productivity. A rapid method was developed for extraction and purification of
      fucoxanthin. The purified fucoxanthin was identified as all-trans-fucoxanthin,
      which exhibited strong antioxidant properties, with the effective concentration
      for 50% scavenging (EC50) of 1,1-dihpenyl-2-picrylhydrazyl (DPPH) radical and
      2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical being 0.14
      and 0.03 mg mL-1, respectively. Our results suggested that O. aurita can be a
      natural source of fucoxanthin for human health and nutrition. 

PMID- 23880938
TI  - Child day-care attendance and Helicobacter pylori infection in the Portuguese
      birth cohort Geracao XXI.
AB  - Helicobacter pylori infection is the most important risk factor for gastric
      cancer. It is acquired predominantly during childhood, and understanding the
      determinants of infection in early life may translate into identifying preventive
      measures. However, the independent role of child day-care attendance remains to
      be understood. The aim of the study was to evaluate the association between child
      day-care attendance and H. pylori infection in early life. The study was nested
      within Geracao XXI, a birth cohort assembled in Portugal. Serum anti-H. pylori
      IgG was quantified using ELISA in 1047 children between the ages of 4 and 5
      years, and information on child day-care attendance since birth was collected.
      Odds ratios and 95% confidence intervals (95% CIs), adjusted for the child's age
      and number of siblings, as well as maternal education and infection status, were
      computed using unconditional logistic regression. The prevalence of H. pylori
      infection was 30.6% (95% CI 27.9-33.6), and it increased significantly with the
      cumulative time of attendance in day-care centers/homes (from 13.2% among never
      attendees to 40.2% among those attending for >36 months; P for trend<0.001). The
      odds ratio was 4.88 (95% CI 2.55-9.35) among those attending these institutions
      for more than 3 years, in comparison with never attendees. H. pylori infection
      remains a frequent and early event in Portugal. Child day-care attendance
      increases the risk of infection, making this setting a target for preventive
      measures. 

PMID- 23880937
TI  - Aniquinazolines A-D, four new quinazolinone alkaloids from marine-derived
      endophytic fungus Aspergillus nidulans.
AB  - Four new quinazolinone alkaloids, namely, aniquinazolines A-D (1-4), were
      isolated and identified from the culture of Aspergillus nidulans MA-143, an
      endophytic fungus obtained from the leaves of marine mangrove plant Rhizophora
      stylosa. The structures of the new compounds were elucidated by spectroscopic
      analysis, and their absolute configurations were determined on the basis of
      chiral HPLC analysis of the acidic hydrolysates. The structure for 1 was
      confirmed by single-crystal X-ray diffraction analysis. All these compounds were
      examined for antibacterial and cytotoxic activity as well as brine shrimp
      (Artemia salina) lethality. 

PMID- 23880939
TI  - Consideration of family history of cancer in medical routine: a survey in the
      primary care setting in Germany.
AB  - Family history of cancer (FHC) is important in the context of cancer prevention
      and risk counselling, but there is a lack of information about its consideration
      in medical routine. We aimed to characterize how FHC is assessed and taken into
      account in the primary care setting in Germany. We conducted a mail survey among
      285 office-based physicians in south-west Germany. We sent a questionnaire to
      randomly selected general practitioners, dermatologists, gastroenterologists,
      gynaecologists, urologists and pulmonologists, asking about collection of
      information on FHC and implications for preventive counselling. A total of 207
      physicians returned the questionnaire (response rate 73%), of whom 71% reported
      asking for FHC routinely, 17% reported using a standardized tool to collect the
      information and 35% reported regularly updating it. Implications of a positive
      FHC for counselling were heterogeneous, with priority on recommendations for
      screening. Referral to genetic counselling was considered by 34% of physicians,
      mainly gastroenterologists and gynaecologists. In the primary care setting in
      Germany, FHC is considered an important topic, but there is a lack of
      standardization in collecting the information and heterogeneity on the
      implications for counselling. Options to improve this situation, such as the
      implementation of standardized tools or centralized counselling systems, are
      needed. 

PMID- 23880940
TI  - Par6 is phosphorylated by aPKC to facilitate EMT.
AB  - The conserved polarity proteins Par6 and aPKC regulate cell polarization
      processes. However, increasing evidence also suggests that they play a role in
      oncogenic progression. During tumor progression, epithelial to mesenchymal
      transition (EMT) delineates an evolutionary conserved process that converts
      stationary epithelial cells into mesenchymal cells, which have an acquired
      ability for independent migration and invasion. In addition to signaling pathways
      that alter genetic programes that trigger the loss of cell-cell adhesion,
      alternative pathways can alter cell plasticity to regulate cell-cell cohesion and
      increase invasive potential. One such pathway involves TGFbeta-induced
      phosphorylation of Par6. In epithelial cells, Par6 phosphorylation results in the
      dissolution of junctional complexes, cytoskeletal remodelling, and increased
      metastatic potential. Recently, we found that aPKC can also phosphorylate Par6 to
      drive EMT and increase the migratory potential of non-small cell lung cancer
      cells. This result has implications with respect to homeostatic and developmental
      processes involving polarization, and also with respect to cancer progression
      particularly since aPKC has been reported to be an oncogenic regulator in various
      tumor cells. 

PMID- 23880941
TI  - The CaMV 35S enhancer has a function to change the histone modification state at
      insertion loci in Arabidopsis thaliana.
AB  - Chromatin regions with different states usually harbor distinct epigenetic
      information, through which gene expression is regulated. Recent studies using
      mammalian cells showed that a chromatin state signature is associated with active
      developmental enhancers, defined by high levels of histone H3 lysine 27
      acetylation (H3K27ac) and strong depletion of H3K27 trimethylation (H3K27me3).
      These findings also imply that active enhancers may play a role in creating a
      chromatin state by changing histone modification markers, which in turn affects
      gene expression. To explore whether an active enhancer in plants affect histone
      modifications, we investigated the cauliflower mosaic virus 35S enhancer (35Senh)
      for understanding its action model in Arabidopsis. We report that the 35Senh has
      a function to change the histone modification pattern at its presenting loci, by
      characterization of the 35Senh activated BREVIPEDICELLUS (BP) silencing lines and
      the randomly selected 35Senh activation tagging lines. By analyzing histone
      modification markers reflecting the plant chromatin state, we show that the
      35Senh is generally correlated with the reduced level of H3K27me3 and the
      increased level of H3K4me3 at the insertion loci. Our data are consistent with
      those in mammals and suggest that the enhancer sequence correlating with the
      active chromatin state signature may be generally present in the eukaryotic
      kingdom. 

PMID- 23880942
TI  - In vitro and in vivo activities of recombinant anthrax protective antigen co
      expressed with thioredoxin in Escherichia coli.
AB  - Because of the central role it plays in the formation of lethal toxin and edema
      toxin, protective antigen (PA) is the principal target for the development of
      vaccines against anthrax. In the present study, we explored and compared the in
      vitro and in vivo activities of recombinant anthrax protective antigen (rPA) and
      receptor binding domain of protective antigen (PA4). As a result, the fully
      soluble rPA and PA4 proteins were successfully expressed in Escherichia coli by
      co-expression with thioredoxin (Trx), and the rPA was active in forming cytotoxic
      lethal toxins, indicating that the rPA protein retains a functionally biological
      activity. Furthermore, immunization with rPA protein induced stronger PA-specific
      immune responses in mice than PA4 protein. The protection elicited by
      immunization with PA4 suggests the presence of common neutralizing epitopes
      between rPA and PA4, but the immunization with rPA protein induced stronger
      neutralizing antibodies and protective levels against challenge with the B.
      anthracis strain A16R than the PA4 protein. The sera neutralizing antibodies
      titers correlated well with anti-PA group ELISA antibodies titers and the in vivo
      protective potency. Based on the results of cell cytotoxicity assays and the
      observed immune responses and protective potency, we concluded that the soluble
      rPA protein retains the in vitro and in vivo functionally biological activity and
      can be developed into a highly effective human subunit vaccine candidate against
      anthrax. 

PMID- 23880943
TI  - Tattooing complicated by multivalvular bacterial endocarditis.
AB  - Tattooing is becoming a popular practice and more commonly done. Although modern
      tattooing is considered a more hygienic and technological version of ancient
      methods, previously reported cases point out the risk of infection after
      tattooing due to use of nonsterile equipment or suboptimal infection-control
      practices. Infective endocarditis (IE) after tattooing has been reported only in
      1 patient with bicuspid aortic valvular disease. Herein, we report a case of
      multivalvular IE secondary to tattooing in a patient without known prior valvular
      heart disease. 

PMID- 23880944
TI  - Angiotensinogen gene variations and LV outflow obstruction in hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: Variations of angiotensinogen (AGT) gene have been associated with
      cardiac hypertrophy. We hypothesized that AGT gene polymorphism may play a
      modifier role in the diversity of left ventricular outflow obstruction. METHODS:
      The polymorphisms of the AGT gene were genotyped in 225 patients with
      hypertrophic cardiomyopathy (HCM) and 243 age-and sex-matched healthy controls.
      The effect of the A and G alleles on the expression of the reporter gene were
      evaluated in vitro using dual-luciferase reporter assays. RESULTS: Our results
      showed that the frequency of the A allele was higher in patients than in controls
      (50.2 % vs. 35.8 %, p < 0.05). Patients carrying the AA and AG genotypes had a
      higher proportion of left ventricular outflow obstruction (30.1 % vs. 17.0 %, p <
      0.05) and heart failure (NYHA functional class III ~ IV, 35.4 % vs. 18.8 %, p <
      0.05) than those carrying the GG genotype had. After adjusted for age, sex, the
      thickness of the interventricular septum, family history of HCM, and sudden
      death, the A allele conferred a 2.4-fold risk for left ventricular outflow
      obstruction than the GG genotype did (adjusted OR = 2.4, 95 %CI 1.2-4.8). The G
      allele suppressed the expression of the reporter gene significantly compared with
      the A allele (p < 0.05). CONCLUSION: AGT gene variations may be genetic modifiers
      for the development of HCM.

PMID- 23880945
TI  - Concealed pheochromocytoma presenting as recurrent acute coronary syndrome with
      STEMI : case report of a patient with hyperthyroidism.
AB  - Pheochromocytomas are rare, primarily benign tumors of chromaffin cells that
      secrete catecholamines. Although they are curable when diagnosed early, they can
      be fatal if undiagnosed or mistreated. Pheochromocytoma causing acute myocardial
      infarction has been reported as presenting with either unstable angina with EKG
      changes and/or non-ST elevation myocardial infarction (NSTEMI), but there have
      been no reported cases of pheochromocytoma presenting as acute ST segment
      elevation myocardial infarction (STEMI) in the setting of hyperthyroidism.
      Herein, we report a 44-year-old female patient with underlying pheochromocytoma
      who presented with multiple episodes of acute coronary syndrome (ACS) including
      an episode of STEMI in the setting of thyroid storm with no obstructive coronary
      artery disease (CAD). 

PMID- 23880946
TI  - Comment on: Triglyceride-to-HDL cholesterol ratio: Predictive value for CHD
      severity and new-onset heart failure.

PMID- 23880947
TI  - [Sleep apnea and heart failure].
AB  - Sleep apnea can influence cardiac function, by which the development of heart
      failure is facilitated. Vice versa, chronic heart failure increases the risk for
      sleep apnea. Consequently, in patients with symptomatic chronic heart failure,
      sleep apnea is a frequent comorbidity occuring in up to 75% of cases. More than
      half of those suffer from central sleep apnea, whereas in the general population,
      obstructive sleep apnea is far more frequent. Both, the obstructive and the
      central sleep apnea lead to oxygen desaturations during the night which are
      followed by increases in serum catecholamines. Possibly, this is the main
      mechanism why the prognosis of patients with symptomatic heart failure and sleep
      apnea is much worse than that of patients without sleep apnea. Therefore, a
      screening of all heart failure patients for sleep apnea is mandatory. Currently,
      large studies are underway which investigate whether the treatment of sleep
      apnea, esp. central sleep apnea, will beneficially influence the clinical course
      of heart failure (SERVE-HF, ADVENT-HF). A new therapeutic approach for central
      sleep apnea is the phrenic nerve stimulation.

PMID- 23880948
TI  - Visualization of left atrial appendage by three-dimensional speckle-tracking
      echocardiography. A case from the MAGYAR-Path Study.

PMID- 23880949
TI  - Unruptured aneurysm of the left sinus of Valsalva compressing the left main
      coronary artery: successful percutaneous treatment.
AB  - Aneurysm of the left sinus of Valsalva is an extremely rare entity. It may be
      asymptomatic and incidentally discovered, or may be symptomatic and manifest
      acutely with compression of adjacent cardiac structures. Encasement of the left
      main coronary artery by such an aneurysm is a recognized but infrequent
      complication that can lead to severe coronary insufficiency. Surgical
      decompression of the left main coronary artery is the standard treatment for such
      conditions. We describe a patient presenting with extrinsic compression of the
      left main coronary artery by a large unruptured aneurysm of the left sinus of
      Valsalva occurring 4 months after unsuccessful surgical repair. Since reoperation
      was considered high-risk for the patient, successful fractional flow reserve- and
      intravascular ultrasound-guided percutaneous treatment of the left main coronary
      artery was performed with implantation of one bare-metal stent. 

PMID- 23880950
TI  - Recurrent takotsubo cardiomyopathy : variable pattern of ventricular involvement.
AB  - BACKGROUND: Takotsubo cardiomyopathy (TTC) is a transient left ventricular (LV)
      dysfunction that predominantly affects older women and has three main variants:
      apical, mid-ventricular, and basal. The recurrence rate of TTC is roughly around
      11 % at 4-year follow-up. The pathogenesis of TTC is not clear and various
      theories have been proposed without concrete evidence. CASE SERIES: We present a
      case series of 3 patients with recurrent TTC involving a different region of the
      ventricle during recurrence. All the patients presented with acute coronary
      syndrome (ACS) during the initial and recurrent episode. At the initial
      presentation, all the patients underwent selective coronary angiography (CA),
      transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging
      (CMR) evaluation. However, the recurrent episodes were diagnosed without the need
      of CA, except in 1 patient who presented with ST-segment elevation myocardial
      infarction. CONCLUSION: Recurrence of TTC is common and can be diagnosed without
      CA in some cases. During recurrence, the regional involvement of the left
      ventricle can vary in the same person. Variable regional involvement in the same
      patient rules out some of the proposed theories on the pathogenesis such as: beta
      receptor gradient, wrap-around left anterior descending, and coronary artery
      spasm.

PMID- 23880951
TI  - Epidemiology: Ethnicity, vitamin D, and CHD.

PMID- 23880952
TI  - Prevention: BNP screening and collaborative care can help to prevent heart
      failure.

PMID- 23880953
TI  - Statins for primary prevention: identifying low-risk individuals.

PMID- 23880954
TI  - Statins for primary prevention: problems with cardiovascular-risk estimation?

PMID- 23880955
TI  - A critical review of cost-effectiveness analyses of vaccinating males against
      human papillomavirus.
AB  - A critical review of cost-effectiveness analyses of HPV vaccination in males was
      conducted and nine studies were identified in different countries. Due to the
      heterogeneity among these studies in terms of modeling approach, vaccination
      strategies, health outcomes considered, assumptions and parameters, limited
      conclusions can be drawn with regard to the absolute cost-effectiveness.
      Nevertheless, key drivers were identified. More favorable cost-effectiveness
      appeared when all HPV-related diseases outcomes were considered, a suboptimal
      vaccine coverage among girls and/or lower vaccine prices were assumed. There was
      a general lack of transparency to fully describe the details of the
      methodological approach of modeling and calibration. Further research should be
      conducted to generate robust evidence-based data sets (HPV-related diseases
      epidemiology, costs and quality of life). The best modeling practice for HPV
      vaccination and how to better capture the true economic value of vaccination
      beyond cost-effectiveness in a broader policy context need to be investigated. 

PMID- 23880956
TI  - Pyridinium-based tripodal chemosensor in visual sensing of AMP in water by
      indicator displacement assay (IDA).
AB  - A simple pyridinium-based tripodal chemosensor, 1, effectively recognizes AMP
      over ATP and ADP through indicator displacement assay (IDA) technique in water at
      pH 6.4. The good recognition of 1 is due to the better accommodation of AMP at
      the core of 1 as well as functional interaction involving hydrogen bonding and
      charge-charge interaction. The sensor 1 also recognizes intracellular AMP.

PMID- 23880957
TI  - Inflammatory mediators alter interleukin-17 receptor, interleukin-12 and -23
      expression in human osteoarthritic and rheumatoid arthritis synovial fibroblasts:
      immunomodulation by vasoactive intestinal Peptide.
AB  - AIMS: To assess the contribution of fibroblast-like synoviocytes (FLS) to the
      inflammatory joint microenvironment under different pathogenic stimuli and their
      potential to respond to interleukin (IL)-17 and to determine whether the
      neuroimmunomodulatory vasoactive intestinal peptide (VIP) is able to modulate IL
      17 receptor (IL-17R) and related cytokines. METHODS: The effect of
      proinflammatory cytokines [tumor necrosis factor alpha (TNFalpha) and IL-17] and
      Toll-like receptor (TLR) ligands [poly(I:C) and lipopolysaccharide (LPS)] on IL
      17R expression and IL-12 and IL-23 production was studied in osteoarthritis (OA)-
      and rheumatoid arthritis (RA)-FLS, involved in Th1/Th17 differentiation. The
      effect of VIP was also determined. IL-17RA, IL-17RC, IL-12p35 and IL-23p19
      expression was measured by real-time polymerase chain reaction. IL-12 and IL-23
      protein levels were measured by ELISA in supernatant cultures. RESULTS: TNFalpha,
      LPS and poly(I:C) induced an increase in IL-17RA in RA-FLS, whereas TNFalpha,
      TNFalpha plus IL-17 and poly(I:C) enhanced IL-17RC transcripts in FLS. VIP
      diminished the upregulated expression of IL-17RA in RA-FLS following TNFalpha and
      poly(I:C). TNFalpha, LPS and poly(I:C) increased IL-12 and IL-23 levels in cells
      derived from patients presenting both pathologies. However, IL-17A DECREASED IL
      12 AND AUGMENTED IL-23. VIP DECREASED IL-12P35 MRNA UPREGULATION BY POLY(I:C) AND
      IL-23P19 TRANSCRIPTS IN LPS-TREATED FLS. CONCLUSIONS: Inflammatory cytokines and
      TLR ligands modulate IL-17R, IL-12 and IL-23 possibly favoring the cross talk
      between FLS and Th1/Th17 cells. The ability of VIP to counteract the enhancing
      effect of proinflammatory molecules on IL-17R and the IL-12 family of cytokines
      corroborates and amplifies the beneficial effect of this endogenous
      neuroimmunopeptide in rheumatic diseases.

PMID- 23880958
TI  - Neural correlates of semantic associations in patients with schizophrenia.
AB  - Patients with schizophrenia have semantic processing disturbances leading to
      expressive language deficits (formal thought disorder). The underlying pathology
      has been related to alterations in the semantic network and its neural
      correlates. Moreover, crossmodal processing, an important aspect of
      communication, is impaired in schizophrenia. Here we investigated specific
      processing abnormalities in patients with schizophrenia with regard to modality
      and semantic distance in a semantic priming paradigm. Fourteen patients with
      schizophrenia and fourteen demographically matched controls made visual lexical
      decisions on successively presented word-pairs (SOA = 350 ms) with direct or
      indirect relations, unrelated word-pairs, and pseudoword-target stimuli during
      fMRI measurement. Stimuli were presented in a unimodal (visual) or crossmodal
      (auditory-visual) fashion. On the neural level, the effect of semantic relation
      indicated differences (patients > controls) within the right angular gyrus and
      precuneus. The effect of modality revealed differences (controls > patients)
      within the left superior frontal, middle temporal, inferior occipital, right
      angular gyri, and anterior cingulate cortex. Semantic distance (direct vs.
      indirect) induced distinct activations within the left middle temporal, fusiform
      gyrus, right precuneus, and thalamus with patients showing fewer differences
      between direct and indirect word-pairs. The results highlight aberrant priming
      related brain responses in patients with schizophrenia. Enhanced activation for
      patients possibly reflects deficits in semantic processes that might be caused by
      a delayed and enhanced spread of activation within the semantic network. Modality
      specific decreases of activation in patients might be related to impaired
      perceptual integration. Those deficits could induce and increase the prominent
      symptoms of schizophrenia like impaired speech processing. 

PMID- 23880959
TI  - CACNA1C genotype explains interindividual differences in amygdala volume among
      patients with schizophrenia.
AB  - Affective deficits are one common denominator of schizophrenia (SZ), bipolar
      disorder (BD) and obsessive compulsive disorder (OCD) with the amygdala indicated
      as one of the major structures involved in emotion regulation. Previous findings
      of differences in amygdala volume between healthy controls and patients with SZ,
      BD or OCD diverge with respect to the affected hemisphere, size and direction of
      the effect. Variability in the CACNA1C gene has been linked to BD, SZ as well as
      structural and functional variation in the amygdala in healthy people and
      patients with BD. We were interested to investigate whether amygdala volumes
      differ between hemispheres, diagnostic or genotype groups, and whether any
      interactive effects exist. We combined genotyping of SNP rs1006737 in CACNA1C
      with structural MRI measurements of relative gray matter (GM) amygdala volume in
      patients with SZ, BD or OCD as well as healthy controls (N Total = 72). The
      CACNA1C genotype showed a significant effect on relative GM amygdala volume in
      patients with SZ. There was a significant left versus right relative GM amygdala
      volume decrease in patients with SZ or BD. The effects of hemisphere and
      diagnosis (controls vs. patients with SZ) on relative GM amygdala volume were
      genotype specific. Our data suggest that the CACNA1C genotype may account for
      some heterogeneity in the effects of hemisphere and diagnosis on amygdala volume
      when comparing patients with SZ and controls and point to disturbed Ca(2+)
      signaling as a plausible mechanism contributing to the pathology in patients with
      SZ. 

PMID- 23880960
TI  - Chemoprevention in Lynch syndrome.
AB  - CAPP1 tested aspirin 600 mg/day and/or resistant starch 30 g/day in 200
      adolescent FAP carriers. Aspirin treatment resulted in a non-significant
      reduction in polyp number and a significant reduction in polyp size among
      patients treated with aspirin for more than 1 year. CAPP2 RCT used the same
      interventions in 937 Lynch syndrome patients, the first RCT to have cancer
      prevention as the primary endpoint. Aspirin did not reduce the risk of colorectal
      neoplasia in a mean treatment period of 29 months but double blind post
      intervention follow-up has revealed 48 participants developed 53 CRCs. Per
      protocol analysis showed 63% fewer colon cancers with aspirin (p = 0.008)
      apparent from 4 years, with a similar effect on other LS cancers. Resistant
      starch was not beneficial at long term followup. CAPP3 will involve a double
      blind dose non-inferiority trial comparing 100, 300 or 600 mg daily in 3,000 gene
      carriers. We can now recommend aspirin in people at high risk of colorectal
      cancer.

PMID- 23880962
TI  - Synthesis and first complexes of C(4/5) P-bifunctional imidazole-2-thiones.
AB  - A synthetic route to C(4/5)-bis(phosphinoyl)imidazole-2-thiones (7d,e) (d: R(1) =
      (n)Bu, R(2) = Me; e: R(1) = n-dodecyl, R(2) = Me) and C(4/5)
      bis(thio/selenophosphinoyl)imidazole-2-thiones (8b,c), (9a,b,e) and 10a (a: R(1)
      = R(2) = Me; b: R(1) = R(2) = Ph, c: R(1) = (i)Pr, R(2) = Me) is presented that
      employs initial C(5) lithiation of mono-phosphinoyl/thiophosphinoyl substituted
      imidazole-2-thiones (3c-e)/(4a-c,e) followed by reaction with
      chlorodiphenylphosphane, leading to mixed phosphinoyl and phosphanyl substituted
      imidazole-2-thiones (5c-e) or mixed thiophosphinoyl and phosphanyl substituted
      imidazole-2-thiones (6a-c,e). Subsequent oxidation of mixed phosphinoyl and
      phosphanyl substituted imidazole-2-thione (5d,e) with H2O2-urea gives the
      bis(phosphinoyl) substituted imidazole-2-thiones (7d,e), and the oxidation of
      mixed thiophosphinoyl and phosphanyl substituted imidazole-2-thione (6a-c,e)
      using H2O2-urea, elemental sulfur or elemental selenium gives a set of mixed P(V)
      chalcogenide substituted imidazole-2-thiones (8b,c), (9a,b,e) and 10a,
      respectively. P(V,V) substituted imidazole-2-thiones 7d and 9a reacted with
      tellurium tetrachloride, titanium tetrachloride or palladium dichloride to give
      complexes 11d, (12d and 12d') and 14a, respectively, having a bidentate chelate
      (11d and 14a) or a monodentate bonding motif (12d,d'). The titanium complexes
      12d,d' slowly and selectively converted into the mono-ethoxy substituted product
      13 possessing a seven membered chelate motif being unprecedented in the titanium
      chemistry of phosphine oxide donor ligands. The compounds were characterized by
      elemental analyses, spectroscopic and spectrometric methods and, in addition, X
      ray diffraction studies in the case of 5c, 7d, 8b, 9a and 13.

PMID- 23880961
TI  - Endometrial tumour BRAF mutations and MLH1 promoter methylation as predictors of
      germline mismatch repair gene mutation status: a literature review.
AB  - Colorectal cancer (CRC) that displays high microsatellite instability (MSI-H) can
      be caused by either germline mutations in mismatch repair (MMR) genes, or non
      inherited transcriptional silencing of the MLH1 promoter. A correlation between
      MLH1 promoter methylation, specifically the 'C' region, and BRAF V600E status has
      been reported in CRC studies. Germline MMR mutations also greatly increase risk
      of endometrial cancer (EC), but no systematic review has been undertaken to
      determine if these tumour markers may be useful predictors of MMR mutation status
      in EC patients. Endometrial cancer cohorts meeting review inclusion criteria
      encompassed 2675 tumours from 20 studies for BRAF V600E, and 447 tumours from 11
      studies for MLH1 methylation testing. BRAF V600E mutations were reported in
      4/2675 (0.1%) endometrial tumours of unknown MMR mutation status, and there were
      7/823 (0.9%) total sequence variants in exon 11 and 27/1012 (2.7%) in exon 15.
      Promoter MLH1 methylation was not observed in tumours from 32 MLH1 mutation
      carriers, or for 13 MSH2 or MSH6 mutation carriers. MMR mutation-negative
      individuals with tumour MLH1 and PMS2 IHC loss displayed MLH1 methylation in
      48/51 (94%) of tumours. We have also detailed specific examples that show the
      importance of MLH1 promoter region, assay design, and quantification of
      methylation. This review shows that BRAF mutations occurs so infrequently in
      endometrial tumours they can be discounted as a useful marker for predicting MMR
      negative mutation status, and further studies of endometrial cohorts with known
      MMR mutation status are necessary to quantify the utility of tumour MLH1 promoter
      methylation as a marker of negative germline MMR mutation status in EC patients.

PMID- 23880965
TI  - The convergence of longitudinal excitons onto the Gamma5 transverse exciton in
      GaN and the thermal activation energy of longitudinal excitons.
AB  - The crystal orientation dependence of GaN excitons was investigated via the
      photoluminescence (PL) technique. The PL emissions at a temperature of 10 K were
      obtained from two experimental configurations where the emission K vector (the
      propagation vector) was either parallel (K ? c) or perpendicular (K ? c) to the
      crystal c-axis. Longitudinal, transverse and donor-bound excitons were observed
      in the two configurations. However, the longitudinal excitons converged onto the
      transverse free exciton Gamma5 in the K?c emission. This behavior was discussed
      in terms of electron screening due to the scattering of electrons moving
      perpendicular to charged dislocation lines. Additionally, the thermal activation
      energy of the longitudinal excitons was calculated from the temperature dependent
      PL measurements collected from the K ? c emission, and was found to be 5 to 6
      times as high as the binding energy of the free excitons. This high energy was
      interpreted tentatively in view of the creation of polaritons in strong exciton
      photon coupling regimes. These findings present fundamental concepts for
      applications such as vertical cavity surface-emitting lasers (VCSELs) and
      polariton lasers. 

PMID- 23880964
TI  - Serum total bilirubin elevation is a predictor of the clinicopathological
      severity of acute appendicitis.
AB  - PURPOSE: Elevation of the serum total bilirubin (STB) level not stemming from
      hepatic dysfunction or biliary obstruction may be seen in cases of acute
      appendicitis. This paper deals with the clinical significance of such elevations.
      METHODS: Data from 410 appendectomized patients classified into two groups (a
      high preoperative STB group and a normal preoperative STB group) were analyzed to
      reveal the significance of preoperative hyperbilirubinemia. We also examined
      whether the preoperative STB level might serve as a risk factor for gangrenous
      appendicitis by a multivariate analysis. RESULTS: Gangrenous appendicitis was
      more common in the high preoperative STB group (p < 0.001). The multivariate
      analysis revealed that an elevated preoperative STB level (odds ratio 1.7919) was
      a risk factor for gangrenous appendicitis. CONCLUSION: In patients with an
      elevated preoperative STB level, it is very likely that the inflammation is
      severe and that the disease has progressed to a severe condition
      histopathologically; therefore, meticulous attention should be paid to the
      selection of the surgical procedure, as well as to the postoperative clinical
      course.

PMID- 23880963
TI  - Analysis of the genomic response of human prostate cancer cells to histone
      deacetylase inhibitors.
AB  - Histone deacetylases (HDACs) have emerged as important targets for cancer
      treatment. HDAC-inhibitors (HDACis) are well tolerated in patients and have been
      approved for the treatment of patients with cutaneous T-cell lymphoma (CTCL). To
      improve the clinical benefit of HDACis in solid tumors, combination strategies
      with HDACis could be employed. In this study, we applied Analysis of Functional
      Annotation (AFA) to provide a comprehensive list of genes and pathways affected
      upon HDACi-treatment in prostate cancer cells. This approach provides an unbiased
      and objective approach to high throughput data mining. By performing AFA on gene
      expression data from prostate cancer cell lines DU-145 (an HDACi-sensitive cell
      line) and PC3 (a relatively HDACi-resistant cell line) treated with HDACis
      valproic acid or vorinostat, we identified biological processes that are affected
      by HDACis and are therefore potential treatment targets for combination therapy.
      Our analysis revealed that HDAC-inhibition resulted among others in upregulation
      of major histocompatibility complex (MHC) genes and deregulation of the mitotic
      spindle checkpoint by downregulation of genes involved in mitosis. These findings
      were confirmed by AFA on publicly available data sets from HDACi-treated prostate
      cancer cells. In total, we analyzed 375 microarrays with HDACi treated and non
      treated (control) prostate cancer cells. All results from this extensive analysis
      are provided as an online research source (available at the journal's website and
      at http://luigimarchionni.org/HDACIs.html). By publishing this data, we aim to
      enhance our understanding of the cellular changes after HDAC-inhibition, and to
      identify novel potential combination strategies with HDACis for the treatment of
      prostate cancer patients.

PMID- 23880966
TI  - Multitracer PET imaging of bone metastases from paraganglioma: peripheral halo of
      uptake on 18F-FLT PET mismatching with central uptake of 18F-FDOPA, 18F
      fluorodopamine, and 18F-FDG.

PMID- 23880967
TI  - Total lesion glycolysis by 18F-FDG PET/CT is a reliable predictor of prognosis in
      soft-tissue sarcoma.
AB  - PURPOSE: Preoperative identification of aggressiveness is important for the
      establishment of a treatment strategy in patients with soft-tissue sarcoma (STS).
      We compared the predictive values of various metabolic parameters derived from
      PET/CT with (18)F-FDG, including maximal standardized uptake value (SUVmax),
      total lesion glycolysis (TLG) and metabolic tumour volume (MTV). METHODS: A total
      of 66 patients with STS who had undergone FDG PET/CT before tumour resection were
      reviewed retrospectively. We determined SUVmax, TLG and MTV to compare their
      value in predicting disease progression, which was defined as local recurrence
      and metastases. Receiver operating characteristic curve (ROC) analysis was used
      to compare the accuracy. Univariate and multivariate analyses of conventional
      clinicopathological variables were used to compare the reliability of the
      metabolic parameters. RESULTS: TLG exhibited greater accuracy than SUVmax or MTV
      in ROC analysis (area under curve, AUC, 0.802, 0.726 and 0.681, respectively).
      The cut-off values for disease progression derived from the AUC data were TLG
      250; SUVmax 6.0, and MTV 40 cm(3). In univariate analysis, TLG (>250) was a more
      significant predictive factor than SUVmax and MTV (P < 0.001, P = 0.031 and P =
      0.022, respectively). TLG was the only meaningful metabolic parameter in the
      multivariate analysis (P = 0.008) other than presence of metastasis at diagnosis
      (P = 0.003). CONCLUSION: TLG is a more accurate predictor of disease progression
      than SUVmax or MTV. TLG enables accurate preoperative assessment of
      aggressiveness comparable with conventional clinicopathological parameters.

PMID- 23880968
TI  - Slow pathway ablation for typical atrioventricular nodal re-entrant tachycardia
      significantly alters the autonomic modulation of atrioventricular conduction.
AB  - PURPOSE: Atrioventricular (AV) conduction turbulence, biphasic dromotropic
      response of AV node to single ventricular premature contraction (VPC), consists
      of early shortening and later prolongation of AV conduction intervals due to the
      direct electrophysiological mechanisms and perturbation in autonomic modulation.
      We investigated the acute effect of radiofrequency catheter ablation of slow
      pathway on AV turbulence. METHODS: The electrophysiological study was performed
      in 18 patients (7 men, mean age 49 +/- 15 years) undergoing catheter ablation for
      AV nodal reentrant tachycardia. The stimulation protocol consisting of series of
      isolated VPC (coupling interval of 273 +/- 23 ms) delivered from right ventricle
      apex during constant atrial pacing at 100 bpm was performed immediately prior to
      and 8 +/- 4 min after successful slow-pathway ablation. Averaged post-VPCs
      profiles of AV conduction intervals were analyzed by purpose-written software.
      The descriptors of AV turbulence, turbulence onset (TOAV), turbulence slope
      (TSAV), and AV recovery (R AV) were assessed. RESULTS: Slow-pathway ablation
      suppressed the AV nodal responsiveness to VPC as evidenced by significant
      reduction of AV turbulence indices: TOAV: -6.4 +/- 7.5 % vs. -4.3 +/- 6.1 % (p <
      0.05); TSAV: 2.0 +/- 2.6 ms/RRi vs. 1.0 +/- 0.7 ms/RRi (p < 0.05); and R AV: 
      13.8 +/- 7.3 % vs. -6.5 +/- 12.7 % (p < 0.05). CONCLUSIONS: Slow-pathway ablation
      significantly attenuated both vagal and non-autonomic modulation of AV nodal
      conduction. This effect is likely due to direct thermal injury of AV node
      associated with the change of properties of AV nodal fast-pathway although
      specific alteration of peri-AV nodal ganglionated plexi or their neural inputs
      into the AV node cannot be excluded.

PMID- 23880969
TI  - Dynamic pupillometry as an autonomic testing tool.
AB  - OBJECTIVE: To determine normal values for pupillometry indices in healthy control
      subjects and to examine these indices in patients with autonomic dysfunction and
      healthy controls. METHODS: Infrared video pupillometry was used to investigate
      the pupil response to a brief light flash in 79 healthy controls, 28 patients
      with normal autonomic function (composite autonomic severity score, CASS < 2),
      and 26 patients with moderate to severe autonomic failure (CASS > 4) seen in our
      autonomic laboratory from January 2008 to June 2011. In six subjects, we examined
      the effects of varying light stimulus intensity and light stimulus duration.
      Descriptive analysis, correlation, and ANCOVA adjusted for age were performed.
      RESULTS: We determined eight indices corresponding to parasympathetic and
      sympathetic pupil function. Baseline pupil diameter (BPD), maximum constriction
      velocity (MCV), absolute constriction amplitude (ACA), and maximum dilation
      velocity (MDV) negatively correlated with age (p < 0.01) among controls. MCV and
      ACA increased with increasing intensity of light stimulus from 3.5 to 112 MUW.
      Indices of parasympathetic pupil innervation (MCV and ACA) were lower in the high
      CASS group compared to others (p < 0.0001). Indices of sympathetic pupil
      function, time to reach 75 % of initial resting diameter during pupillary
      dilation (T3/4), and dilation velocity at T3/4 (DV3/4) did not differ
      significantly in the three study groups. However, T3/4 corrected for the
      magnitude of pupillary constriction (T3/4:ACA) was higher in the high CASS group
      suggesting sympathetic dysfunction in that group (p = 0.0003). CONCLUSIONS:
      Indices of pupillomotor function significantly differ between patients with
      moderate to severe autonomic failure and healthy controls.

PMID- 23880970
TI  - New-generation multifocal intraocular lens for pediatric cataract.
AB  - BACKGROUND/AIMS: To evaluate multifocal intraocular lens (MIOL) implantation in
      children. METHODS: This is a retrospective study evaluating refractive, visual
      and safety results of MIOL in pediatric cataract surgery. Average follow-up was
      25.73 +/- 10.5 months. Surgery included 12 o'clock clear corneal incision,
      anterior capsulorhexis, lens material aspiration and MIOL implantation (SN6AD3;
      Alcon). RESULTS: We included 34 cataract eyes of 26 pediatric patients aged 2-15
      years, of which 14 (54%) were unilateral. Best near visual acuity (BNVA) and best
      distance visual acuity (BDVA) improved significantly in 100% of eyes (p =
      0.0001). BDVA was above 0.8 in 31.25% (5/16) of bilateral cases. Significant
      stereopsis improvement was observed postoperatively in bilateral cases only (p =
      0.01). CONCLUSION: MIOL implantation is a safe alternative to monofocal
      pseudophakia for pediatric cataract with a very low complication rate.
      Significant BNVA, BDVA and stereopsis improvement can be achieved, particularly
      in bilateral cases. MESSAGE: This study shows significant BDVA, BNVA and
      stereopsis improvement, especially in bilateral cases, after MIOL implantation
      for pediatric cataracts.

PMID- 23880971
TI  - Randomized, double-blind, placebo-controlled, dose-escalating phase I, healthy
      subjects study of intravenous OPN-305, a humanized anti-TLR2 antibody.
AB  - Upregulation of Toll-like receptor 2 (TLR2) plays a critical role in inflammation
      associated with ischemia/reperfusion-induced tissue damage. OPN-305 is the first
      humanized IgG4 monoclonal antibody against TLR2 in development and is intended
      for the prevention of reperfusion injury following renal transplantation and
      other indications. A phase I, single-center, prospective randomized, double
      blind, placebo-controlled study was performed to evaluate single ascending doses
      of OPN-305 in 41 healthy male subjects (age range: 19-58 years) randomized to OPN
      305 or placebo across six cohorts. OPN-305 was well tolerated across all doses,
      with no elevations in endogenous cytokines. A dose-proportional increase in
      maximum serum concentration (Cmax) was observed, with area under the curve
      increasing in a greater-than-dose-proportional manner with increasing elimination
      half-life. OPN-305 produced full TLR2 receptor blockade on CD14(+)CD45(+) cells
      (monocytes), from 14 (0.5 mg/kg) to >90 (10 mg/kg) days, with a linear effect on
      the duration of inhibition of interleukin-6 release after TLR2 stimulation.

PMID- 23880972
TI  - Anatomical position of hyaluronic acid gel following injection to the eyebrow.
AB  - PURPOSE: To examine with histology the anatomical location of hyaluronic acid gel
      injected to the eyebrow of cadaver specimens. METHODS: The authors dissected 5
      fresh hemifacial cadaver specimens following preperiosteal injection of
      hyaluronic acid gel to the eyebrow. Following tissue fixation, full-thickness
      soft-tissue sections were obtained followed by histologic examination. RESULTS:
      Histologic examination revealed the location of hyaluronic acid gel at the
      intended preperiosteal plane in all 5 specimens. Very dense retro-orbicularis
      oculi fat septa appeared to limit the anterior displacement of filler in each
      specimen. CONCLUSIONS: This study provides a greater understanding of the
      anatomical barriers and boundaries that help to determine, in part, the
      anatomical position of hyaluronic acid gel when injected to the preperiosteal
      eyebrow. The high degree of histologically confirmed consistency of product
      location of eyebrow injections noted in this study stands in contrast to the
      variability of position of gel injected in the infraorbital hollows.

PMID- 23880973
TI  - A modified lacrimal sac implant for high-risk dacryocystorhinostomy.
AB  - PURPOSE: The reported 5% of patients with nasolacrimal duct obstruction who fail
      dacryocystorhinostomy likely include patients with severe mucosal disease or
      anatomical anomalies. The technique described herein avoids mucosal anastomosis
      and minimizes mucosal manipulation by inserting a permanent silicone conduit from
      the lacrimal sac into the nasal cavity. METHODS: This retrospective review of 9
      surgical cases was performed with institutional review board approval. Six
      patients underwent 9 surgeries (3 sequentially bilateral) for dacryocystitis. Two
      patients had Wegener granulomatosis, 1 had pemphigoid, 1 sarcoidosis, 1 Rosai
      Dorfman disease, and 1 congenital choanal atresia with chronic neonatal
      dacryocystitis. In each case, a modified Rains sinus stent was inserted through
      an external lacrimal sac incision with the draining end positioned in the nasal
      cavity. Two patients underwent concurrent canalicular intubation with Guibor
      silicone stents to prevent internal punctum obstruction by the lacrimal sac
      implant. Recurrence of symptoms, patient comfort, and modified Rains stent
      stability and patency were evaluated. RESULTS: Mean follow up was 30 months
      (range 7-59 months). The modified Rains stent remained stable and patent in 7 of
      9 cases, and symptoms resolved in 8 of 9 cases. In 1 patient with sarcoidosis,
      the modified Rains stent became repeatedly obstructed with nasal secretions and
      ultimately dislodged after intranasal manipulation by a physician unfamiliar with
      the surgery. In no other case did the patient experience recurrent infection, and
      in those cases, epiphora resolved entirely. In the patient with pemphigoid, one
      of the modified Rains stents extruded 6 months postoperatively, but his symptoms
      remained controlled. No adverse reaction to the implant material was seen.
      CONCLUSIONS: A Rains silicone frontal sinus stent can be modified for
      implantation into the lacrimal sac and can safely and effectively drain the
      lacrimal sac into the nose in patients with severe mucosal disease or anatomical
      anomalies. Additional study and a stent specifically designed for this
      application will likely improve outcomes.

PMID- 23880974
TI  - Dacryoendoscopic findings in the lacrimal passage in failed
      dacryocystorhinostomy.
AB  - PURPOSE: To examine the appearance of the lacrimal passage using dacryoendoscopy
      in failed dacryocystorhinostomies, examining the relationship between the remnant
      lacrimal sac mucosa and the obstruction tissue, and to detect canalicular
      obstruction. METHODS: Twenty failed dacryocystorhinostomies (4 right and 16 left)
      in 19 Japanese patients (8 males and 11 females) aged 36 to 81 years (average,
      69.5 years) were reviewed. Dacryoendoscopy was used to examine the lacrimal
      passage of the failed dacryocystorhinostomies. RESULTS: An occluded space was
      found with no adhesion between the remnant lacrimal sac mucosa and the fibrous
      obstruction tissue in every failed dacryocystorhinostomy. None of the lacrimal
      canaliculi or the common internal ostia was obstructed. CONCLUSIONS: A space
      without adhesion between the remnant lacrimal sac mucosa and the obstruction
      tissue was visualized in all the failed dacryocystorhinostomies. No canalicular
      stenosis was seen, including the common internal ostium, in this cases. Based on
      these results, endoscopic revision for failed dacryocystorhinostomies is a safe
      procedure, performed without orbital fat prolapse.

PMID- 23880975
TI  - Microbiologic trends and biofilm growth on explanted periorbital biomaterials: a
      30-year review.
AB  - PURPOSE: To investigate microbiologic trends and role of biofilm on periorbital
      biomaterials surgically explanted for recalcitrant infection. METHODS: A search
      of the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine
      microbiology laboratory electronic database was conducted from 1980 to 2010.
      Culture results were analyzed from submitted periorbital biomaterials explanted
      for nonresolving infections or exposure. Random select samples cultured during
      the study were sent for electron microscopy. RESULTS: Twenty-one explanted
      biomaterials were identified from 18 patients. Five orbital plate implants
      included 2 made of nylon, 1 of porous polyethylene, 1 of silicone, and 1
      metallic. Of 4 anophthalmic socket sphere implants, 2 were silicone, 1 was porous
      polyethylene, and 1 was poly-2-hydroxyethyl methacrylate. Lacrimal intubation
      devices included 10 silicone stents and 2 pyrex glass Jones tubes. All
      biomaterials were culture positive with 40 total isolates identified. The most
      common organisms overall were Mycobacterium chelonae (N = 9), Staphylococcus
      aureus (N = 8), and Pseudomonas aeruginosa (N = 3). One hundred percent of
      orbital spheres had Gram-positive organisms, 90% of lacrimal silicone stents grew
      atypical mycobacterium, and 60% of orbital plates were culture positive for yeast
      species. Mixed organism growth was documented on 58% of the specimens. Ten of 12
      implants (83%) examined with electron microscopy exhibited organisms encased in
      glycocalyx, suggestive of biofilm. CONCLUSIONS: A diverse array of microorganisms
      can colonize biomaterials implanted within the orbit and lacrimal drainage
      system. The authors' study showed that the majority of infected periocular and
      orbital alloplastic implants display biofilm when studied with electron
      microscopy (83%). The cultured organism type depended on the implant location and
      composition. Most infected silicone lacrimal stents grew atypical mycobacterium,
      whereas infected orbital fracture repair plates demonstrated yeast species.
      Biofilms are known to be antibiotic resistant, explaining the need to explant
      most infected alloplastic implants. Further research concerning treatment of
      biofilms may prevent explantation and improve surgical outcomes.

PMID- 23880976
TI  - Optic nerve cyst-like formation presenting as a delayed complication of optic
      nerve sheath fenestration.
AB  - Two patients with idiopathic intracranial hypertension underwent optic nerve
      sheath fenestration. One patient developed decreased vision and choroidal folds 1
      month postoperatively. The other patient developed proptosis and pain 9 months
      postoperatively. Neuroimaging showed a cyst-like structure adjacent to the optic
      nerve in each patient. In each case, symptoms and signs resolved after surgical
      excision of the structure. 

PMID- 23880977
TI  - Incidence of bilateral Marcus Gunn jaw-wink.
AB  - This case report describes the unusual finding of bilateral Marcus Gunn jaw-wink.
      Only a few bilateral jaw-wink patients have been published as case reports. The
      authors dispute this notion as portrayed in the literature that a bilateral wink
      is a rare entity. A thorough review of prior case series on congenital ptosis and
      jaw-wink demonstrates that bilateral involvement is more common than previously
      thought. A supplemental video shows the classic action of lateral pterygoid
      contraction causing ipsilateral eyelid retraction. 

PMID- 23880978
TI  - Ignition of eyelash extensions during routine minor eyelid surgery.
AB  - Preoperative patient questionnaires enquiring about the presence of prosthetics
      are routine. Eyelash extensions are not part of standard preoperative
      questionnaires. This case illustrates how this impacts patient safety during
      minor eyelid surgery. 

PMID- 23880979
TI  - Determination of the phase diagram of water and investigation of the electrical
      transport properties of ices VI and VII.
AB  - The phase diagram of water near the ice VI-ice VII-liquid triple point and
      electrical transport properties of these ices have been studied by in situ
      electrical conductivity measurements in a diamond anvil cell. The obtained phase
      boundary between ices VI and VII and the melting curve for these ices are in
      accord with most previous results. The different properties and amount of
      orientational defects in ice VI and ice VII are associated with abrupt changes in
      conductivity when a phase transition from ice VI to ice VII occurs. The
      electrical transport mechanisms of these two ice polymorphs can be understood in
      terms of the conduction of the already existing ions and Bjerrum defects. 

PMID- 23880980
TI  - Acute hepatitis A in an elderly patient after care worker travel to high
      endemicity country.
AB  - Hepatitis A virus (HAV) is considered one of the most important vaccine
      preventable diseases in travelers. HAV spreads from person to person via the
      fecal-oral route and gives rise to an estimated 1.4 million cases worldwide each
      year. In developing countries with poor sanitary conditions people tend to be
      infected during childhood and have few symptoms, whereas in developed countries
      with good sanitary conditions fewer people develop immunity during childhood.
      This leads to susceptible populations of adults, who are also more prone to
      severe complications. Here we describe two confirmed cases of hepatitis A
      associated with a nursing home. The index case was a care worker who had recently
      traveled to a high-endemicity country, and the second case was a resident at the
      nursing home where the index case worked. Both cases had an identical genotype
      IIIA strain, consistent with a transmission event. Current policy does not
      include a requirement for hepatitis A vaccine in care workers who travel to high
      endemicity countries despite the fact that infected care workers can potentially
      spread the disease to elderly patients and other groups at risk of severe
      complications from HAV infection. We suggest that employers should consider
      hepatitis A vaccine upon employment; particularly in care workers who plan to
      visit areas where HAV is known to be endemic. 

PMID- 23880981
TI  - Ultrasound-guided peripheral venous access: a systematic review of randomized
      controlled trials.
AB  - OBJECTIVE: To systematically review the current literature on the effect of using
      ultrasound (US) guidance for the placement of peripheral intravenous (PIV)
      catheters in patients with difficult access. MATERIALS AND METHODS: A systematic
      search was performed for the keywords ultrasonography, catheterization, and
      peripheral vein. A systematic review was performed on randomized-controlled
      studies comparing the use of dynamic US guidance with the conventional landmark
      technique. The primary outcome was the success rate of PIV placement and the
      secondary outcomes included the number of attempts and time to successful PIV
      placement. RESULTS: A total of 1778 titles were identified from the search and
      the review identified 50 potentially relevant studies that were reviewed
      comprehensively; six articles were included in the final review. The six studies
      enrolled a total of 316 patients, 153 in the control group and 163 in the US
      group. Two of the studies reported a significantly higher success rate for US on
      the basis of initial success or the overall success rate. The two pediatric
      studies found that time to successful cannulation was shorter and fewer attempts
      were required to achieve success for patients randomized to US compared with the
      traditional method. The six studies included were found to vary significantly in
      the definition of difficult venous access, recording of procedure time,
      definition of success rate, and other important factors, making a meta-analysis
      inappropriate. CONCLUSION: On the basis of this review, routine use of US
      guidance for PIV placement is not strongly supported by the literature.

PMID- 23880982
TI  - Long-term effects of acute low-dose ionizing radiation on the neonatal mouse
      heart: a proteomic study.
AB  - Epidemiological studies establish that children and young adults are especially
      susceptible to radiation-induced cardiovascular disease (CVD). The biological
      mechanisms behind the elevated CVD risk following exposure at young age remain
      unknown. The present study aims to elucidate the long-term effects of ionizing
      radiation by studying the murine cardiac proteome after exposure to low and
      moderate radiation doses. NMRI mice received single doses of total body (60)Co
      gamma-irradiation on postnatal day 10 and were sacrificed 7 months later. Changes
      in cardiac protein expression were quantified using isotope-coded protein label
      and tandem mass spectrometry. We identified 32, 31, 66, and 34 significantly
      deregulated proteins after doses of 0.02, 0.1, 0.5, and 1.0 Gy, respectively. The
      four doses shared 9 deregulated proteins. Bioinformatics analysis showed that
      most of the deregulated proteins belonged to a limited set of biological
      categories, including metabolic processes, inflammatory response, and
      cytoskeletal structure. The transcription factor peroxisome proliferator
      activated receptor alpha was predicted as a common upstream regulator of several
      deregulated proteins. This study indicates that both adaptive and maladaptive
      responses to the initial radiation damage persist well into adulthood. It will
      contribute to the understanding of the long-term consequences of radiation
      induced injury and developmental alterations in the neonatal heart. 

PMID- 23880983
TI  - Young men with poor cardiorespiratory fitness combined with lower testosterone
      have high levels of oxidized LDL lipids--being fit alters this relationship.
AB  - PURPOSE: We hypothesized that lower androgen status together with poor physical
      fitness associates with atherogenic lipid profile and oxidative stress. METHODS:
      Volunteered young men (N = 846, mean age 25.1 +/- 4.6 years) were categorized
      into unfit, average fit, and fit groups according to tertiles of maximal oxygen
      uptake, series of muscle endurance tests, and maximal upper and lower body
      strength. Furthermore, concentrations of serum testosterone (TT) and free
      testosterone (FT) were determined to divide participants into lower and higher
      testosterone (loTT, hiTT) and free testosterone (loFT, hiFT) subgroups, using
      medians as cut-off points. The participants were divided into subgroups according
      to Fitness * Testosterone (Unfit/Average Fit/ Fit * Low/High TT/FT), and the
      concentrations of serum lipids and ox-LDL were measured. RESULTS: The loTT/unfit
      cardiorespiratory subgroup had 29% higher concentration of ox-LDL compared with
      the loTT/fit cardiorespiratory subgroup (p = .044). The loTT / unfit
      cardiorespiratory subgroup had a significantly higher ratio of ox-LDL/HDL
      cholesterol compared with the other five TT subgroups (p < .05, in all). While ox
      LDL showed a gradual form of decrease from unfit to fit in loTT cardiorespiratory
      subgroups, no differences were seen in muscular fitness or maximal strength
      (upper and lower body) subgroups. CONCLUSIONS: Young men with poor
      cardiorespiratory fitness together with lower levels of TT have higher
      concentrations of ox-LDL. Good cardiorespiratory fitness combined with lower
      androgen levels is not related to atherogenic lipid profile. The combination of
      poor muscular fitness, or maximal muscle strength, and lower TT levels does not
      cause atherogenic lipid profile.

PMID- 23880984
TI  - Differential expression of dipeptidyl peptidase IV in human versus cynomolgus
      monkey skin eccrine sweat glands.
AB  - Dipeptidyl peptidase IV (DPP4) is a peptidase whose inhibition is beneficial in
      Type II diabetes treatment. Several evidences suggest potential implication of
      DPP4 in skin disorders such as psoriasis, keloids and fibrotic skin diseases
      where its inhibition could also be beneficial. DPP4 expression in human skin was
      described mainly in dermal fibroblasts and a subset of keratinocytes in the basal
      layer. Of importance in the perspective of preclinical experimentation, DPP4
      distribution in skin of non-human primate species has not been documented. This
      report evidences unexpected differences between a set of human and cynomolgus
      monkey skin samples revealing a major expression of DPP4 in eccrine sweat glands
      of cynomolgus monkeys but not in humans. This represents a unique distinctive
      feature compared to the conserved expression of dipeptidyl peptidases 8 and 9 and
      potential relevant DPP4 substrates such as neuropeptide Y (NPY) and receptors
      (NPY-receptor 1 and Neurokinin receptor). Finally the observation that cathepsin
      D, an unrelated protease, shows the opposite expression compared to DPP4 (present
      in human but not in cynomolgus monkey eccrine sweat glands) could indicate that
      human eccrine sweat glands evolved a divergent protease repertoire compared to
      non-human primates. These unexpected differences in the eccrine sweat glands
      protease repertoire will need to be confirmed extending the analysis to a major
      number of donors but could imply possible biochemical divergences, reflecting the
      functional evolution of the glands and the control of their activity. Our
      findings also demonstrate that non-human primates studies aiming at understanding
      DPP4 function in skin biology are not readily translatable to human. 

PMID- 23880985
TI  - Aquaporins in the adult mouse submandibular and sublingual salivary glands.
AB  - Aquaporins (AQPs) is a family of membrane bound water channels found in most
      tissues. In addition to contribute to transepithelial water movement, AQPs are
      shown to be involved in a variety of processes such as proliferation, cell
      migration, and apoptosis. In salivary glands, it is well known that AQP5 plays an
      important role in fluid secretion. In recent years, several AQPs that demonstrate
      specific expression trends during development have been found in the mouse
      submandibular gland (SMG). In this study, we wanted to further investigate the
      presence and localization of the AQP family in the adult mouse SMG in addition to
      the less studied sublingual gland. Real time PCR and Western blot demonstrated
      the presence of AQP3, 4, 8, 9, and 11 transcripts and proteins. AQP1 and AQP7
      were shown to be localized in endothelial cells, while AQP4 was found in the
      satellite cells of the parasympathetic ganglia in both glands. The result from
      this study shows that AQPs are found in defined subpopulations of cells in
      salivary glands, providing novel insights to their specific roles in salivary
      glands. 

PMID- 23880986
TI  - Modified boron subphthalocyanines with stable electrochemistry and tuneable
      bandgaps.
AB  - The synthesis of boron subphthalocyanines (BsubPc) from modified phthalonitriles
      is reported. The BsubPcs have intense red-shifted absorption compared to normal
      BsubPcs and readily tuneable optoelectronic properties including enhanced
      electrochemical stability and the presence of up to two reversible
      electrochemical reductions. 

PMID- 23880987
TI  - Soft magnonic modes in two-dimensional permalloy antidot lattices.
AB  - Soft magnonic modes in permalloy antidot lattices with a fixed lattice constant a
      = 420 nm and circular hole diameters ranging between 140 and 260 nm are
      investigated both experimentally and theoretically. The frequency dependence of
      magnonic modes on the magnetic field intensity, applied along the vertical rows
      of holes, was measured by Brillouin light scattering from thermally excited spin
      waves. All the detected modes exhibit a monotonic frequency evolution with
      respect to the applied magnetic field, with the exception of the two lowest
      frequency modes which become soft at a given critical field and exhibit a finite
      frequency gap. It has been shown, by means of micromagnetic simulations based on
      the dynamical matrix method, that the mode softening is strictly related to the
      rotation of the static magnetization from the hard to the easy axis marking a
      reorientational and continuous phase transition. In addition, the different
      frequency trend of the fundamental mode and of the corresponding mode localized
      along the horizontal rows of holes as a function of the aspect ratio is explained
      in terms of the opposite demagnetizing field experienced by the two modes. 

PMID- 23880988
TI  - Opening medallion from Portugal's Museu de Anestesiologia.

PMID- 23880989
TI  - Hypnos, god of sleep.

PMID- 23880990
TI  - Asylum & Main: from wells to Whoppers.

PMID- 23880992
TI  - Does helium act on vascular endothelial function in humans?

PMID- 23880991
TI  - Conventional and kilohertz-frequency spinal cord stimulation produces intensity-
      and frequency-dependent inhibition of mechanical hypersensitivity in a rat model
      of neuropathic pain.
AB  - BACKGROUND: Spinal cord stimulation (SCS) is a useful neuromodulatory technique
      for treatment of certain neuropathic pain conditions. However, the optimal
      stimulation parameters remain unclear. METHODS: In rats after L5 spinal nerve
      ligation, the authors compared the inhibitory effects on mechanical
      hypersensitivity from bipolar SCS of different intensities (20, 40, and 80% motor
      threshold) and frequencies (50, 1 kHz, and 10 kHz). The authors then compared the
      effects of 1 and 50 Hz dorsal column stimulation at high- and low-stimulus
      intensities on conduction properties of afferent Aalpha/beta-fibers and spinal
      wide-dynamic-range neuronal excitability. RESULTS: Three consecutive daily SCS at
      different frequencies progressively inhibited mechanical hypersensitivity in an
      intensity-dependent manner. At 80% motor threshold, the ipsilateral paw
      withdrawal threshold (% preinjury) increased significantly from pre-SCS measures,
      beginning with the first day of SCS at the frequencies of 1 kHz (50.2 +/- 5.7%
      from 23.9 +/- 2.6%, n = 19, mean +/- SEM) and 10 kHz (50.8 +/- 4.4% from 27.9 +/-
      2.3%, n = 17), whereas it was significantly increased beginning on the second day
      in the 50 Hz group (38.9 +/- 4.6% from 23.8 +/- 2.1%, n = 17). At high intensity,
      both 1 and 50 Hz dorsal column stimulation reduced Aalpha/beta-compound action
      potential size recorded at the sciatic nerve, but only 1 kHz stimulation was
      partially effective at the lower intensity. The number of actions potentials in C
      fiber component of wide-dynamic-range neuronal response to windup-inducing
      stimulation was significantly decreased after 50 Hz (147.4 +/- 23.6 from 228.1 +/
      39.0, n = 13), but not 1 kHz (n = 15), dorsal column stimulation. CONCLUSIONS:
      Kilohertz SCS attenuated mechanical hypersensitivity in a time course and
      amplitude that differed from conventional 50 Hz SCS, and may involve different
      peripheral and spinal segmental mechanisms.

PMID- 23880993
TI  - In reply.

PMID- 23880994
TI  - Differentiating inspiratory and expiratory valve malfunctions.

PMID- 23880995
TI  - In reply.

PMID- 23880996
TI  - The airway paradigm: what really changed?

PMID- 23880997
TI  - In reply.

PMID- 23881002
TI  - We're on the right path...

PMID- 23881005
TI  - Assessing working memory via N-back task in euthymic bipolar I disorder patients:
      a review of functional magnetic resonance imaging studies.
AB  - Bipolar disorder (BD) is a chronic and highly disabling mood disorder, associated
      with the highest suicide rate among psychiatric disorders. Even though
      neurobiological bases of BD have still to be further elucidated, recent
      neuroimaging studies provided compelling evidence about functional correlates of
      cognitive deficits in BD patients, with working memory (WM) impairment being one
      of the most commonly reported findings. Such dysfunctions are likely to persist
      beyond acute phases of the illness, so they qualify as endophenotypic markers for
      the disorder. This review sought to synthesize, through a MEDLINE search up to
      December 2012, published functional magnetic resonance imaging (fMRI) studies on
      WM networks, conducted through N-back task in euthymic BD I patients and
      including a control comparison group. Eight studies meeting the search criteria
      were identified. Despite heterogeneity across findings, particularly in relation
      to task performance (i.e. accuracy and reaction time), most studies reported a
      loss of connectivity in BD patients' prefrontal networks, traditionally involved
      in WM, as well as patterns of abnormal activation in the dorso/ventrolateral
      prefrontal cortex, other prefrontal areas and the parietal and temporal cortex.
      These findings suggest the involvement of intact secondary systems in order to
      overcome lack of integrity across WM circuits in BD patients. Further
      investigation in the field is warranted. 

PMID- 23881004
TI  - Measurement techniques for magnetic resonance imaging of fast relaxing nuclei.
AB  - In this review article, techniques for sodium ((23)Na) magnetic resonance imaging
      (MRI) are presented. These techniques can also be used to image other nuclei with
      short relaxation times (e.g., (39)K, (35)Cl, (17)O). Twisted projection imaging,
      density-adapted 3D projection reconstruction, and 3D cones are preferred because
      of uniform k-space sampling and ultra-short echo times. Sampling density weighted
      apodization can be applied if intrinsic filtering is desired. This approach leads
      to an increased signal-to-noise ratio compared to postfiltered acquisition in
      cases of short readout durations relative to T 2 (*) relaxation time. Different
      MR approaches for anisotropic resolution are presented, which are important for
      imaging of thin structures such as myocardium, cartilage, and skin. The third
      part of this review article describes different methods to put more weighting
      either on the intracellular or the extracellular sodium signal by means of
      contrast agents, relaxation-weighted imaging, or multiple-quantum filtering. 

PMID- 23881007
TI  - Response to letter to the editor: accuracy of segmental multi-frequency
      bioelectrical impedance analysis for assessing whole-body and appendicular fat
      mass and lean soft tissue mass in frail women aged 75 years and older.

PMID- 23881006
TI  - Prediction of fat-free mass using bioelectrical impedance analysis in young
      adults from five populations of African origin.
AB  - BACKGROUND/OBJECTIVES: Bioelectrical impedance analysis (BIA) is used in
      population and clinical studies as a technique for estimating body composition.
      Because of significant under-representation in existing literature, we sought to
      develop and validate predictive equation(s) for BIA for studies in populations of
      African origin. SUBJECTS/METHODS: Among five cohorts of the Modeling the
      Epidemiologic Transition Study, height, weight, waist circumference and body
      composition, using isotope dilution, were measured in 362 adults, ages 25-45 with
      mean body mass indexes ranging from 24 to 32. BIA measures of resistance and
      reactance were measured using tetrapolar placement of electrodes and the same
      model of analyzer across sites (BIA 101Q, RJL Systems). Multiple linear
      regression analysis was used to develop equations for predicting fat-free mass
      (FFM), as measured by isotope dilution; covariates included sex, age, waist,
      reactance and height(2)/resistance, along with dummy variables for each site.
      Developed equations were then tested in a validation sample; FFM predicted by
      previously published equations were tested in the total sample. RESULTS: A site
      combined equation and site-specific equations were developed. The mean
      differences between FFM (reference) and FFM predicted by the study-derived
      equations were between 0.4 and 0.6 kg (that is, 1% difference between the actual
      and predicted FFM), and the measured and predicted values were highly correlated.
      The site-combined equation performed slightly better than the site-specific
      equations and the previously published equations. CONCLUSIONS: Relatively small
      differences exist between BIA equations to estimate FFM, whether study-derived or
      published equations, although the site-combined equation performed slightly
      better than others. The study-derived equations provide an important tool for
      research in these understudied populations.

PMID- 23881008
TI  - Surveillance of patients with bladder cancer following cystectomy: yield of CT
      urography.
AB  - PURPOSE: To determine the yield of CT urography (CTU) in the surveillance of
      patients with bladder cancer following cystectomy. MATERIALS AND METHODS: In this
      IRB-approved, HIPAA-compliant, retrospective study of 5,404 CT urograms performed
      at our institution between March 2000 and February 2011, 225 CT urograms were
      performed in 105 patients [79 men, 26 women; mean age 65 years (43-85)] following
      cystectomy for bladder cancer. Median follow-up after cystectomy was 63 months
      (range 1-234), median time between cystectomy and CTU was 39 months (range 0
      229), median follow-up after CTU was 34 months (range 1-111). CTU examinations
      were reviewed by two radiologists in consensus and findings were categorized into
      those related to surgery, locoregional recurrence, metastases, or metachronous
      upper tract urothelial tumor (UTT). FINDINGS: Findings were present in 69 (65.7
      %) of 105 patients, including findings related to surgery in 60 (57.1 %)
      patients, locoregional recurrence or metastatic disease in 21 (20 %) patients,
      and UTT in 3 (2.9 %) patients. Of surgery-related findings, hydronephrosis
      (23/105, 21.9 %) and parastomal hernia (17/105, 16.2 %) were the most common
      findings. Visceral metastases (16/105, 15.2 %) and lymph node metastases (13/105,
      12.4 %) were the most common manifestations of recurrent disease. CONCLUSION: CTU
      findings in the surveillance of patients with bladder cancer after cystectomy are
      common and include those related to surgery, spread of the disease, and
      metachronous tumors. Our study supports current published guidelines on the use
      of CTU in these patients.

PMID- 23881009
TI  - Dirhodium complexes: determination of absolute configuration by the exciton
      chirality method using VCD spectroscopy.
AB  - Inherently chiral dinuclear rhodium complexes have been synthesized from the well
      known dirhodium(II)-acetate and chiral/achiral amino acids. These complexes have
      a twisted paddlewheel structure due to axial chirality. Chiral induction could be
      observed when the ligands were chiral, opposite to the case of achiral ligands,
      where a racemic mixture was formed. The racemic mixture was separated by chiral
      HPLC-ECD. The stereochemical properties of these complexes were determined by VCD
      spectroscopy supported by theoretical calculations at the DFT level. We present a
      simple route to determine the absolute configuration by an exciton chirality
      method using VCD spectroscopy.

PMID- 23881010
TI  - Embracing the lazy days of summer... or should we?

PMID- 23881011
TI  - Healthcare changes are ahead.

PMID- 23881014
TI  - Creating an "I can do attitude" toward orthopaedic nurse certification:
      convenient, efficient, and effective.
AB  - As hospitals and healthcare have become specialized, so has nursing. Orthopaedic
      nurse certification is an example of this specialization. The purpose of this
      article is to describe the outcomes of one specialty hospital's implemented plan
      designed to encourage and support nurses seeking to demonstrate expertise in
      orthopaedic nursing practice. A review course was developed with attention to
      potential barriers and concerns that were identified in the review of literature.
      Successful resolution of problems encountered with staff nurses becoming
      orthopaedic nurse certified are described. Participants in the first 2 sessions
      passed the examination on the first attempt at a rate of 100% and 88%, which
      exceeds the national rate of 86.5% (Orthopaedic Nurse Certification Board, 2011,
      retrieved from http://oncb.org/certification-statistics). Since initiation of the
      program, the number of "orthopaedic nurse certification" nurses has nearly
      tripled in this orthopaedic specialty hospital. 

PMID- 23881015
TI  - What do orthopaedic nurses do? Implications of the role delineation study for
      certification.
AB  - The Orthopaedic Nurses Certification Board (ONCB) conducts a role delineation
      study (RDS) every 5 years. Results identify tasks performed by orthopaedic
      registered nurses, nurse practitioners, and clinical nurse specialists, and
      musculoskeletal health conditions commonly seen by patients under their care.
      PURPOSE: The purpose of the study was to define current practice patterns among
      orthopaedic nurses and validate content for future certification examinations.
      METHOD: An online survey methodology was used to identify task and knowledge
      statements that represented orthopaedic nursing practice. FINDINGS: Of 5,634 e
      mails sent, 1,194 valid responses were returned (response rate 22.7%). This is
      consistent with results of the Orthopaedic Nurses Certification Board's 2007 RDS
      (23.3% response rate) and is considered acceptable for an RDS. CONCLUSION: Survey
      results were analyzed with assistance of psychometric staff at Applied
      Measurement Professionals, Inc., and used to review and revise examination
      specifications for the 3 certification programs. New specifications were
      implemented with March 2012 testing.

PMID- 23881017
TI  - Managing bone metastasis in the patient with advanced cancer.
AB  - Bone is the third most common site of cancer metastasis resulting in pain and
      other serious morbidities that can affect one's quality of life. The orthopaedic
      patient with bone metastasis faces many challenges and has complex nursing care
      needs. Managing care involves astute assessment skills, knowledge of treatments
      including medication, surgery, and radiation therapy, and recognition of serious
      complications such as fracture, spinal cord compression, and hypercalcemia.
      Nurses play a vital role in the patient treatment plan by implementing
      interventions that promote positive outcomes and prevent injuries. 

PMID- 23881019
TI  - Effects of tourniquet pressure on rehabilitation outcomes in patients undergoing
      total knee arthroplasty.
AB  - BACKGROUND: Although studies determinate that the tourniquet and high tourniquet
      pressure applications lead to several complications and decelerate the
      rehabilitation, there was not any study investigating the effects of tourniquet
      pressure on rehabilitation outcomes and postoperative complications. PURPOSE: To
      investigate the effects of the minimal and conventional tourniquet inflation
      pressures application on rehabilitation outcomes in patients undergoing total
      knee arthroplasty (TKA). METHODS: Thirty-eight patients with unilateral primary
      TKA were included in the study. All patients underwent standardized inpatient
      physiotherapy during their hospital stay and followed by home-based exercise
      program. We used the Visual Analog Scale to quantify knee pain, Iowa Level of
      Assistance Scale, and Iowa Ambulation Velocity Scale to determine physical
      function. The dates of ability to perform straight leg raise actively and to
      reach 70 degrees  of knee flexion were recorded. Hospital for Special Surgery
      knee score and range of motion of all patients were assessed preoperatively, at
      6, 12, and 26 weeks, postoperatively. RESULTS: There was a significant difference
      in terms of Iowa Level of Assistance Scale on the postoperative 2nd and 6th days
      in favor of minimal inflation pressure group, in addition to the significant
      difference in pain level at discharge and the date of 70 degrees  knee flexion
      reach in favor of the same group, but Hospital for Special Surgery score and
      movement were similar at 6, 12, and 26 weeks. There was no significant difference
      between the groups in the date of performing straight leg raise. CONCLUSIONS: We
      conclude that TKA operations with a tourniquet application at lower inflation
      pressures might minimize the complications of tourniquet use and the patients can
      gain more rapidly early functional mobility.

PMID- 23881020
TI  - Is there a safe coital position after a total hip arthroplasty?
AB  - The population of patients receiving posterior total hip arthroplasty (THA) is
      growing among middle-aged adults. Through literature review and a survey of
      colleagues, it has been presented that patients and medical staff tend not to
      discuss the effects of sexual activity on posterior THA. So the question arises,
      is the supine position (missionary position) recommended over other coital
      positions in preventing posterior hip dislocations after a THA? The literature
      review included a search for full-text research studies from the peer-reviewed
      journals from 2002 to 2007. The studies affirm that the supine position is the
      safest coital position after a THA. Sexual relations are essential to the health,
      quality of life, and well-being of individuals. Because of the importance that
      sexual relations play in one's life, it is imperative that healthcare providers
      (nurse practitioners) educate their patients regarding sexual activity after a
      posterior THA. 

PMID- 23881022
TI  - Epidural abscess with spinal cord compression.

PMID- 23881025
TI  - Analysis of risk factors and survival in pediatric high-grade spinal cord
      astrocytoma: a population-based study.
AB  - BACKGROUND/AIMS: Primary pediatric high-grade spinal cord astrocytomas are rare
      neoplasms with poor prognoses. Using the Surveillance, Epidemiology, and End
      Results (SEER) database, we analyzed prognostic factors and survival. METHODS:
      Pediatric patients with histologically confirmed diagnoses of primary high-grade
      spinal cord astrocytoma (WHO grade III-IV) from 1973 to 2008 in the SEER database
      were studied. Univariate and multivariate Cox proportional hazards models were
      used to analyze the relationship between demographic, tumor grade, and treatment
      factors on survival. RESULTS: Median survival in the 48 patient cohort was 10
      months. Increasing age and higher tumor grade were found to be significantly
      associated with higher mortality. For children aged <7, 7-12, and 13-18 years,
      median survival was 22, 11, and 8 months, respectively. For children with
      anaplastic astrocytoma (WHO grade III), median survival was 12 months, compared
      with 7 months for those with glioblastoma multiforme (WHO grade IV). This study
      did not find a statistically significant relationship between sex, race, presence
      of radiation therapy or extent of surgical resection and mortality. CONCLUSION:
      Survival in primary pediatric high-grade spinal cord astrocytomas was positively
      associated with younger age and lower tumor grade. Survival was not associated
      with other demographic or treatment modality factors.

PMID- 23881026
TI  - Manipulating spin hyper-polarization by means of adiabatic switching of a spin
      locking RF-field.
AB  - We propose a technique for transferring the multiplet spin polarization (CIDNP or
      PHIP, or one created by any other method), which is the mutual entanglement of
      spins, into net hyper-polarization with respect to the direction of a high
      magnetic field by slowly (adiabatically) switching-off a strong external RF-field
      with a specially selected frequency. The net hyper-polarized molecules can then
      be used in NMR spectroscopy or imaging for strong signal enhancement. 

PMID- 23881027
TI  - Cutting a fine figure: On the use of thin sections in electron microscopy to
      quantify autophagy.
AB  - Over the last few years, two guideline articles have been published with
      recommendations for assessing autophagy. These articles contained advice on
      quantification of autophagy by electron microscopy and proposed using thin slices
      for quantifying autophagic structures. Here, we expand on what can and cannot be
      quantified using single 2D slices and give some suggestions for efficient and
      minimally biased approaches for quantifying this fascinating and important
      process. We recommend that the journal Autophagy follow other journals in
      demanding stringent random sampling design and application of unbiased design
      based quantification when reviewing submitted manuscripts. 

PMID- 23881028
TI  - Oxidative stress induced by HIV-1 reverse transcriptase modulates the enzyme's
      performance in gene immunization.
AB  - HIV-1 infection induces chronic oxidative stress. The resultant neurotoxicity has
      been associated with Tat protein. Here, we for the first time describe the
      induction of oxidative stress by another HIV-1 protein, reverse transcriptase
      (RT). Expression of HIV-1 RT in human embryonic kidney cells generated potent
      production of the reactive oxygen species (ROS), detected by the fluorescence
      based probes. Quantitative RT-PCR demonstrated that expression of RT in HEK293
      cells induced a 10- to 15-fold increased transcription of the phase II
      detoxifying enzymes human NAD(P)H: quinone oxidoreductase (Nqo1) and heme
      oxygenase 1 (HO-1), indicating the induction of oxidative stress response. The
      capacity to induce oxidative stress and stress response appeared to be an
      intrinsic property of a vast variety of RTs: enzymatically active and
      inactivated, bearing mutations of drug resistance, following different routes of
      processing and presentation, expressed from viral or synthetic expression
      optimized genes. The total ROS production induced by RT genes of the viral origin
      was found to be lower than that induced by the synthetic/expression-optimized or
      chimeric RT genes. However, the viral RT genes induced higher levels of ROS
      production and higher levels of HO-1 mRNA than the synthetic genes per unit of
      protein in the expressing cell. The capacity of RT genes to induce the oxidative
      stress and stress response was then correlated with their immunogenic
      performance. For this, RT genes were administered into BALB/c mice by intradermal
      injections followed by electroporation. Splenocytes of immunized mice were
      stimulated with the RT-derived and control antigens and antigen-specific
      proliferation was assessed by IFN-gamma/IL-2 Fluorospot. RT variants generating
      high total ROS levels induced significantly stronger IFN-gamma responses than the
      variants inducing lower total ROS, while high levels of ROS normalized per unit
      of protein in expressing cell were associated with a weak IFN-gamma response.
      Poor gene immunogenicity was also associated with a high (per unit of protein)
      transcription of antioxidant response element (ARE) dependent phase II
      detoxifying enzyme genes, specifically HO-1. Thus, we have revealed a direct link
      between the propensity of the microbial proteins to induce oxidative stress and
      their immunogenicity.

PMID- 23881029
TI  - The bat genome: GC-biased small chromosomes associated with reduction in genome
      size.
AB  - Bats are distinct from other mammals in their small genome size as well as their
      high metabolic rate, possibly related to flight ability. Although the genome
      sequence has been published in two species, the data lack cytogenetic
      information. In this study, the size and GC content of each chromosome are
      measured from the flow karyotype of the mouse-eared bat, Myotis myotis (MMY). The
      smaller chromosomes are GC-rich compared to the larger chromosomes, and the
      relative proportions of homologous segments between MMY and human differ among
      the MMY chromosomes. The MMY genome size calculated from the sum of the
      chromosome sizes is 2.25 Gb, and the total GC content is 42.3%, compared to human
      and dog with 41.0 and 41.2%, respectively. The GC-rich small MMY genome is
      characterised by GC-biased smaller chromosomes resulting from preferential loss
      of AT-rich sequences. Although the association between GC-rich small chromosomes
      and small genome size has been reported only in birds so far, we show in this
      paper, for the first time, that the same phenomenon is observed in at least one
      group of mammals, implying that this may be a mechanism common to genome
      evolution in general.

PMID- 23881030
TI  - Earlier diagnosis of breast cancer: focusing on symptomatic women.

PMID- 23881031
TI  - Earlier diagnosis of breast cancer outside of a screening programme.

PMID- 23881032
TI  - Epidemiology: Time to ESCAPE the city? Air pollution linked to lung cancer.

PMID- 23881034
TI  - Skin cancer: Basal cell carcinoma--pay your money, take your choice.
AB  - Superficial basal cell carcinomas are a common challenge in clinical dermatology
      because they are frequent and surgical approaches tend to scar. A large
      randomized trial comparing three nonsurgical approaches has shown that all had
      similar clinical outcomes - so, you pay your money and take your choice.

PMID- 23881033
TI  - Image-guided cancer surgery using near-infrared fluorescence.
AB  - Paradigm shifts in surgery arise when surgeons are empowered to perform surgery
      faster, better and less expensively than current standards. Optical imaging that
      exploits invisible near-infrared (NIR) fluorescent light (700-900 nm) has the
      potential to improve cancer surgery outcomes, minimize the time patients are
      under anaesthesia and lower health-care costs largely by way of its improved
      contrast and depth of tissue penetration relative to visible light. Accordingly,
      the past few years have witnessed an explosion of proof-of-concept clinical
      trials in the field. In this Review, we introduce the concept of NIR fluorescence
      imaging for cancer surgery, examine the clinical trial literature to date and
      outline the key issues pertaining to imaging system and contrast agent
      optimization. Although NIR seems to be superior to many traditional imaging
      techniques, its incorporation into routine care of patients with cancer depends
      on rigorous clinical trials and validation studies. 

PMID- 23881036
TI  - Mammography screening and women with symptomatic breast cancer.

PMID- 23881037
TI  - Lung cancer: Defining standard of care for performance status 2--don't rush.
AB  - The standard treatment for patients with advanced-stage non-small-cell lung
      cancer with a performance status of 2 is unclear because of the heterogeneity of
      this population. Although a recent trial suggests that carboplatin plus
      pemetrexed improves survival as compared to single-agent pemetrexed, we should be
      cautious when defining new standards of treatment on the basis of single small
      trials.

PMID- 23881035
TI  - Luminal breast cancer: from biology to treatment.
AB  - Oestrogen receptor (ER)-positive--or luminal--tumours represent around two-thirds
      of all breast cancers. Luminal breast cancer is a highly heterogeneous disease
      comprising different histologies, gene-expression profiles and mutational
      patterns, with very varied clinical courses and responses to systemic treatment.
      Despite adjuvant endocrine therapy and chemotherapy treatment for patients at
      high risk of relapse, both early and late relapses still occur, a fact that
      highlights the unmet medical needs of these patients. Ongoing research aims to
      identify those patients who can be spared adjuvant chemotherapy and who will
      benefit from extended adjuvant hormone therapy. This research also aims to
      explore the role of adjuvant bisphosphonates, to interrogate new agents for
      targeting minimal residual disease, and to address endocrine resistance. Data
      from next-generation sequencing studies have given us new insight into the
      biology of luminal breast cancer and, together with advances in preclinical
      models and the availability of newer targeted agents, have led to the testing of
      rationally chosen combination treatments in clinical trials. However, a major
      challenge will be to make sense of the large amount of patient genomic data that
      is becoming increasingly available. This analysis will be critical to our
      understanding how intertumour and intratumour heterogeneity can influence
      treatment response and resistance.

PMID- 23881038
TI  - Targeted therapies: Time to shift the burden of proof for oncogene-positive
      cancer?
AB  - Rearrangements of the ALK gene have been associated with sensitivity to
      crizotinib and other kinase inhibitors with activity against ALK. The phase III
      PROFILE 1007 randomized study of crizotinib versus chemotherapy has demonstrated
      that crizotinib is superior to standard second-line chemotherapy in ALK-positive
      non-small-cell lung cancer.

PMID- 23881039
TI  - [Letter to the editor concerning the article "Fractures of the lower extremity in
      the emergency room"].

PMID- 23881040
TI  - Cytotoxicity of cultured macrophages exposed to antimicrobial zinc oxide (ZnO)
      coatings on nanoporous aluminum oxide membranes.
AB  - Zinc oxide (ZnO) is a widely used commercial material that is finding use in
      wound healing applications due to its antimicrobial properties. Our study
      demonstrates a novel approach for coating ZnO with precise thickness control onto
      20 nm and 100 nm pore diameter anodized aluminum oxide using atomic layer
      deposition (ALD). ZnO was deposited throughout the nanoporous structure of the
      anodized aluminum oxide membranes. An 8 nm-thick coating of ZnO, previously noted
      to have antimicrobial properties, was cytotoxic to cultured macrophages. After 48
      h, ZnO-coated 20 nm and 100 nm pore anodized aluminum oxide significantly
      decreased cell viability by ~65% and 54%, respectively, compared with cells grown
      on uncoated anodized aluminum oxide membranes and cells grown on tissue culture
      plates. Pore diameter (20-200 nm) did not influence cell viability. 

PMID- 23881041
TI  - Characteristics of shaken baby syndrome in a regional Japanese children's
      hospital.
AB  - PURPOSE: To report the characteristics of Japanese shaken baby syndrome (SBS) in
      a regional Japanese children's hospital and verify previously reported
      idiosyncratic features that differ from those of SBS in Western countries: (1) a
      considerably higher frequency of mothers as perpetrators, (2) older ages of
      abusive parents, and (3) a higher rate of premature infant birth. METHODS: We
      reviewed medical charts obtained between 2002 and 2012 at Nagano Children's
      Hospital, Japan. RESULTS: Thirty-seven SBS cases with abusive head trauma were
      found, among which 11 (30 %) of the perpetrators were mothers, 9 (24 %) fathers,
      3 (8 %) brothers, and 14 (37 %) involved both parents. A history of premature
      birth was present in 2 (5 %) of the cases. The mean age of the mother was 32.4
      years and that of the father was 31.3 years. CONCLUSION: The clinical
      characteristics of Japanese SBS in this study are largely comparable to those
      seen in Western countries. Compared with the previously reported idiosyncratic
      features, there was a decreased predominance of mothers as perpetrators of SBS,
      suggestive of an increasing culpability of fathers. We also noticed that the
      ratio of premature births was more similar to those seen in Western surveys,
      while the mean ages of abusive Japanese parents remained older. Such varying
      results warrant a further nationwide survey.

PMID- 23881042
TI  - Antemortem and postmortem fentanyl concentrations: a case report.

PMID- 23881043
TI  - Why Telestroke networks? Rationale, implementation and results of the Stroke
      Eastern Saxony Network.
AB  - Stroke is the third leading cause of death and the leading cause of acquired long
      term disability in Europe and North America. Intravenous (IV) thrombolysis with
      alteplase and organized inpatient (stroke unit) care have been shown to improve
      stroke patients' functional outcomes. However, stroke unit care is not area-wide
      available and thrombolysis rates are low, partly due to limited stroke
      thrombolysis expertise in smaller community hospitals. Telemedical stroke
      networks (Telestroke network) with remote video assessment of patients and brain
      computed tomography (CT) scans by stroke neurologists have been shown to increase
      IV thrombolysis rates and functional outcomes of patients in smaller community
      hospitals. Our article summarizes the rationale, clinical, and currently
      published scientific results of Telestroke networks with special respect to the
      telemedical Stroke Eastern Saxony Network (SOS-NET), which has been established
      by the Dresden University Stroke Center (DUSC) in July 2007. From July 2007 to
      December 2012, 3416 teleconsultations have been performed within the SOS-NET. 

PMID- 23881044
TI  - Relationship between oral D-amphetamine self-administration and ratings of
      subjective effects: do subjective-effects ratings correspond with a progressive
      ratio measure of drug-taking behavior?
AB  - The abuse potential of drugs has traditionally been determined in humans using
      subjective ratings of drug effects. However, drug self-administration procedures
      also provide valuable information about the reinforcing effects of drugs that may
      contribute to their potential for abuse. Although ratings of subjective effects
      and drug self-administration data are generally concordant, some divergent
      findings have been reported. Therefore, the aim of the present analysis was to
      directly investigate the relationship between the subjective-effects profile and
      self-administration of oral D-amphetamine in healthy volunteers with a history of
      stimulant use or abuse, using Pearson's correlational analyses. The results
      indicated that positive subjective and reinforcing effects significantly
      increased as a function of D-amphetamine dose. Further, significant, but modest,
      correlations were observed between ratings of six of 17 total items (Any Effect,
      High, Like Drug, Good Effects, Willing to Pay For, and Willing to Take Again) and
      D-amphetamine self-administration under a progressive-ratio schedule of
      reinforcement. The current findings suggest that, at least under the current set
      of conditions with oral D-amphetamine, subjective-effects measures and drug self
      administration data likely provide different but complimentary information about
      abuse potential. The most informative findings will thus be obtained from studies
      that use ratings of subjective effects and drug self-administration methods. 

PMID- 23881045
TI  - Abuse-related effects of u-opioid analgesics in an assay of intracranial self
      stimulation in rats: modulation by chronic morphine exposure.
AB  - Intracranial self-stimulation (ICSS) is an operant procedure in which responding
      is maintained by electrical brain stimulation. Stimulation frequency can be
      varied rapidly to maintain a wide range of baseline response rates, and drugs'
      effects can be evaluated simultaneously on both low ICSS rates maintained by low
      stimulation frequencies and high ICSS rates maintained by high stimulation
      frequencies. ICSS 'facilitation' indicates drug-induced increases in low ICSS
      rates and is often considered an abuse-related effect, whereas ICSS 'depression'
      indicates decreases in high ICSS rates and may indicate abuse-limiting effects.
      This study examined the roles of u-agonist efficacy and of previous u-agonist
      exposure as determinants of u-agonist effects on ICSS in rats with electrodes
      implanted into the medial forebrain bundle. The high-efficacy, intermediate
      efficacy, and low-efficacy u agonists methadone, fentanyl, and nalbuphine were
      tested during escalating regimens of morphine exposure (vehicle, 3.2, and 18
      mg/kg/day). During vehicle treatment, methadone and fentanyl primarily depressed
      ICSS, whereas nalbuphine produced weak facilitation that was not dose dependent.
      Chronic morphine produced tolerance to ICSS depression and increased expression
      of ICSS facilitation. These results suggest that u-agonist exposure increases the
      expression of abuse-related ICSS facilitation by u agonists with a broad range of
      efficacies at u receptors. 

PMID- 23881047
TI  - PbCu3TeO7: an S = 1/2 staircase kagome lattice with significant intra-plane and
      inter-plane couplings.
AB  - We have synthesized polycrystalline and single-crystal samples of PbCu3TeO7 and
      studied its properties via magnetic susceptibility, chi(T), and heat-capacity,
      Cp(T), measurements and also electronic structure calculations. Whereas the
      crystal structure is suggestive of the presence of a quasi-2D network of Cu(2+)
      (S = 1/2) buckled staircase kagome layers, the chi(T) data show magnetic
      anisotropy and three magnetic anomalies at temperatures TN1 ~ 36 K, TN2 ~ 25 K,
      and TN3 ~ 17 K. The chi(T) data follow the Curie-Weiss law above 200 K and a
      Curie-Weiss temperature thetaCW ~- 150 K is obtained. The data deviate from the
      simple Curie-Weiss law below 200 K, which is well above TN1, suggesting the
      presence of competing magnetic interactions. The magnetic anomaly at TN3 appears
      to be of first order from magnetization measurements, although our Cp(T) results
      do not display any anomaly at TN3. The hopping integrals obtained from our
      electronic structure calculations suggest the presence of significant intra
      kagome (next-nearest neighbor and diagonal) and inter-kagome couplings. These
      couplings take the PbCu3TeO7 system away from a disordered ground state and lead
      to long-range order, in contrast to what might be expected for an ideal
      (isotropic) 2D kagome system. 

PMID- 23881046
TI  - Sexual Dimorphism in the Brain of the Monogamous California Mouse (Peromyscus
      californicus).
AB  - Sex differences in behavior and morphology are usually assumed to be stronger in
      polygynous species compared to monogamous species. A few brain structures have
      been identified as sexually dimorphic in polygynous rodent species, but it is
      less clear whether these differences persist in monogamous species. California
      mice are among the 5% or less of mammals that are considered to be monogamous and
      as such provide an ideal model to examine sexual dimorphism in neuroanatomy. In
      the present study we compared the volume of hypothalamic- and limbic-associated
      regions in female and male California mice for sexual dimorphism. We also used
      tyrosine hydroxylase (TH) immunohistochemistry to compare the number of dopamine
      neurons in the ventral tegmental area (VTA) in female and male California mice.
      Additionally, tract tracing was used to accurately delineate the boundaries of
      the VTA. The total volume of the sexually dimorphic nucleus of the preoptic area
      (SDN-POA), the principal nucleus of the bed nucleus of the stria terminalis
      (BNST), and the posterodorsal medial amygdala (MEA) was larger in males compared
      to females. In the SDN-POA we found that the magnitude of sex differences in the
      California mouse were intermediate between the large differences observed in
      promiscuous meadow voles and rats and the absence of significant differences in
      monogamous prairie voles. However, the magnitude of sex differences in MEA and
      the BNST were comparable to polygynous species. No sex differences were observed
      in the volume of the whole brain, the VTA, the nucleus accumbens or the number of
      TH-ir neurons in the VTA. These data show that despite a monogamous social
      organization, sexual dimorphisms that have been reported in polygynous rodents
      extend to California mice. Our data suggest that sex differences in brain
      structures such as the SDN-POA persist across species with different social
      organizations and may be an evolutionarily conserved characteristic of mammalian
      brains.

PMID- 23881048
TI  - Structure of the C-terminal region of the Frizzled receptor 1 in detergent
      micelles.
AB  - The C-terminal domains of the Frizzleds (FZDs) contain a short conserved motif
      (KTXXXW). It has been demonstrated that FZDs interacted with the PDZ domain of
      the cytoplasmic proteins such as Dishevelled through this motif and mutations in
      this motif disrupted Wnt/beta-catenin signaling. We carried out structural
      studies for a peptide derived from the C-terminal domain of the FZD1 in different
      solvents using circular dichroism and solution NMR spectroscopy. Our results
      showed that this domain was unstructured in an aqueous solution and formed a
      helical structure in detergent micelles. Fluorescence studies suggested that the
      tryptophan residue (W630) in the motif interacted with micelles. The solution
      structure of the peptide in sodium dodecyl sulfate micelles was determined and an
      amphipathic helix was identified. This helix may have similar function to the
      helix 8 of other G protein-coupled receptors. 

PMID- 23881049
TI  - Searching for stable Si(n)C(n) clusters: combination of stochastic potential
      surface search and pseudopotential plane-wave Car-Parinello simulated annealing
      simulations.
AB  - To find low energy Si(n)C(n) structures out of hundreds to thousands of isomers
      we have developed a general method to search for stable isomeric structures that
      combines Stochastic Potential Surface Search and Pseudopotential Plane-Wave
      Density Functional Theory Car-Parinello Molecular Dynamics simulated annealing
      (PSPW-CPMD-SA). We enhanced the Sunders stochastic search method to generate
      random cluster structures used as seed structures for PSPW-CPMD-SA simulations.
      This method ensures that each SA simulation samples a different potential surface
      region to find the regional minimum structure. By iterations of this automated,
      parallel process on a high performance computer we located hundreds to more than
      a thousand stable isomers for each Si(n)C(n) cluster. Among these, five to 10 of
      the lowest energy isomers were further optimized using B3LYP/cc-pVTZ method. We
      applied this method to Si(n)C(n) (n = 4-12) clusters and found the lowest energy
      structures, most not previously reported. By analyzing the bonding patterns of
      low energy structures of each Si(n)C(n) cluster, we observed that carbon
      segregations tend to form condensed conjugated rings while Si connects to
      unsaturated bonds at the periphery of the carbon segregation as single atoms or
      clusters when n is small and when n is large a silicon network spans over the
      carbon segregation region.

PMID- 23881050
TI  - The effect of PAMAM dendrimers on the antibacterial activity of antibiotics with
      different water solubility.
AB  - Erythromycin (EM) and tobramycin (TOB) are well-known and widely used
      antibiotics, belonging to different therapeutic groups: macrolide and
      aminoglycoside, respectively. Moreover, they possess different solubility: EM is
      slightly soluble and TOB is freely soluble in water. It was previously
      demonstrated that PAMAM dendrimers enhanced the pharmacological activity of
      antifungal drugs by increasing their solubility. Therefore, it appears
      interesting to investigate the effect of PAMAM-NH2 and PAMAM-OH dendrimers
      generation 2 (G2) and generation 3 (G3) on the antibacterial activity of
      antibiotics with different water solubility. In this study it was shown that the
      aqueous solubility of EM was significantly increased by PAMAM dendrimers (PAMAM
      NH2 and PAMAM-OH caused about 8- and 7- fold solubility increases, respectively).
      However, it was indicated that despite the increase in the solubility, there was
      only slight influence on the antibacterial activity of EM (2- and 4-fold
      decreases in the MBC values of EM in the presence of PAMAM-OH G3 and PAMAM-NH2 G2
      or G3 for strains of Staphylococcus aureus were noted, respectively). It was also
      found that there was no influence of PAMAM on the antibacterial activity of
      hydrophilic TOB.

PMID- 23881051
TI  - Recent trends in bioorthogonal click-radiolabeling reactions using fluorine-18.
AB  - The increasing application of positron emission tomography (PET) in nuclear
      medicine has stimulated the extensive development of a multitude of novel and
      versatile bioorthogonal conjugation techniques especially for the radiolabeling
      of biologically active high molecular weight compounds like peptides, proteins or
      antibodies. Taking into consideration that the introduction of fluorine-18
      (t(1/2) = 109.8 min) proceeds under harsh conditions, radiolabeling of these
      biologically active molecules represents an outstanding challenge and is of
      enormous interest. Special attention has to be paid to the method of 18F
      introduction. It should proceed in a regioselective manner under mild
      physiological conditions, in an acceptable time span, with high yields and high
      specific activities. For these reasons and due to the high number of functional
      groups found in these compounds, a specific labeling procedure has to be
      developed for every bioactive macromolecule. Bioorthogonal strategies including
      the Cu-assisted Huisgen cycloaddition and its copper-free click variant, both
      Staudinger Ligations or the tetrazine-click reaction have been successfully
      applied and represent valuable alternatives for the selective introduction of
      fluorine-18 to overcome the afore mentioned obstacles. This comprehensive review
      deals with the progress and illustrates the latest developments in the field of
      bioorthogonal labeling with the focus on the preparation of radiofluorinated
      building blocks and tracers for molecular imaging.

PMID- 23881052
TI  - Phenolic content and antioxidant activities of burr parsley (Caucalis platycarpos
      L.).
AB  - Since C. platycarpos contains a wide variety of antioxidants, in the present
      study total flavonoid and phenolic acid content as well as antioxidative activity
      of various C. platycarpos extracts were investigated. The results obtained show a
      significant polyphenol content and antioxidant activity of the investigated
      plant. Moreover, a positive correlation between antioxidant activity and content
      of flavonoids and phenolic acids was found, indicating the responsibility of
      these compounds for the antioxidant effectiveness of C. platycarpos extracts and
      making C. platycarpos a good potential source of natural antioxidants. 

PMID- 23881053
TI  - MYB transcription factors regulate glucosinolate biosynthesis in different organs
      of Chinese cabbage (Brassica rapa ssp. pekinensis).
AB  - In this study, we investigated the expression of seven MYB transcription factors
      (a total of 17 genes that included Dof1.1, IQD1-1, MYB28, MYB29, MYB34, MYB51,
      and MYB122 and their isoforms) involved in aliphatic and indolic glucosinolate
      (GSL) biosynthesis and analyzed the aliphatic and indolic GSL content in
      different organs of Chinese cabbage (Brassica rapassp. Pekinensis). MYB28 and
      MYB29 expression in the stem was dramatically different when compared with the
      levels in the other organs. MYB34, MYB122, MYB51, Dof1.1, and IQD1-1 showed very
      low transcript levels among different organs. HPLC analysis showed that the
      glucosinolates (GSLs) consisted of five aliphatic GSLs (progoitrin, sinigrin,
      glucoalyssin, gluconapin, and glucobrassicanapin) and four indolic GSLs (4
      hydroxyglucobrassicin, glucobrassicin, 4-methoxygluco-brassicin, and
      neoglucobrassicin). Aliphatic GSLs exhibited 63.3% of the total GSLs content,
      followed by aromatic GSL (19.0%), indolic GSLs (10%), and unknown GSLs (7.7%) in
      different organs of Chinese cabbage. The total GSL content of different parts
      (ranked in descending order) was as follows: seed > flower > young leaves > stem
      > root > old leaves. The relationship between GSLs accumulation and expression of
      GSLs biosynthesis MYB TFs genes in different organs may be helpful to understand
      the mechanism of MYB TFs regulating GSL biosynthesis in Chinese cabbage. 

PMID- 23881054
TI  - Diorganotin(IV) derivatives of N-methyl p-fluorobenzo-hydroxamic acid:
      preparation, spectral characterization, X-ray diffraction studies and antitumor
      activity.
AB  - Three diorganotin(IV) complexes of the general formula R2Sn[RcC(O)N(RN)O] (Rc =
      aryl, RN = Alkyl) have been synthesized by refluxing in toluene the corresponding
      diorganotin(IV) oxides with the free ligand N-methyl p-fluorobenzohydroxamic
      acid, using a Dean and Stark water separator. The ligand was derived from the
      reaction of the corresponding p-fluorobenzoyl chloride and N-methylhydroxylamine
      hydrochloride in the presence of sodium hydrogen carbonate. The isolated free
      ligand and its respective diorganotin compounds have been characterized by
      elemental analysis, IR and 1H-, 13C-, 119Sn-NMR spectroscopies. The crystal
      structures of the diorganotin complexes have been confirmed by single crystal X
      ray diffraction methods. The investigations carried out on the diorganotin(IV)
      complexes of N-methyl p-fluorobenzohydroxamic acid confirmed a 1:2 stoichiometry.
      The complex formation took place through the O,O-coordination via the carbonyl
      oxygen and subsequent deprotonated hydroxyl group to the tin atom. The crystal
      structures of three diorganotin complexes were determined and were found to adopt
      six coordination geometries at the tin centre with coordination to two ligand
      moieties. 

PMID- 23881055
TI  - Transformations in plasma membranes of cancerous cells and resulting consequences
      for cation insertion studied with molecular dynamics.
AB  - Structural and energetic transformations in the plasma membrane of a cancerous
      cell are investigated together with related consequences for the insertion of
      small cationic compounds. Molecular dynamics simulations are performed with an
      empirical force field on two membrane models that represent the membrane of a
      cancerous cell (M-Cancer) and of a healthy cell (M-Eukar), respectively. An eight
      fold increase of negatively charged phosphatidylserine in the external membrane
      layer as well as a reduction of cholesterol concentration by half is taken into
      account to describe the membrane transformation. Three additional reference
      membranes are prepared and consist of pure phosphatidylcholine (M-PC), where 20%
      is replaced with phosphatidylserine (M-PC0.8S0.2), and where 34% is replaced with
      cholesterol (M-PC0.66Ch0.34), respectively. Moreover, the free energy released by
      inserting octadecylmethylimidazolium (OMIM(+)), a cation found in a class of
      common ionic liquids, into M-Eukar, M-Cancer as well as into the three reference
      model membranes is derived by applying thermodynamic integration. We find that
      the presence of serine improves the solvation of the membrane through favorable
      electrostatic interactions with solvated sodium ions, where a significant number
      of sodium ions are capable of penetrating the upper polar layer of the membrane.
      However, the insertion free energy of OMIM(+) does not seem to be influenced by
      serine in the membrane. Furthermore, a significant serine induced structural
      reorganization of the membrane is not observed. In contrast, a reduction of
      cholesterol in the membrane models leads to smaller lipid surface densities,
      thinner membranes as well as less ordered and less stretched lipids as expected.
      We also observe that cholesterol reduction leads to a rougher membrane surface
      and an increased solvent accessibility of the hydrophobic membrane core. Membrane
      insertion of OMIM(+) becomes significantly more favorable in the absence of
      cholesterol, with an increased insertion free energy release of 7.1 kJ mol(-1) in
      M-Cancer compared to M-Eukar. Overall, the results suggest only a minor influence
      of serine on membrane organization but do not rule out an influence on cation
      insertion through a stronger cation adsorption to the membrane surface. In
      contrast, cholesterol seems to impede OMIM(+) insertion by increasing the density
      of polar lipids on the membrane surface and by flattening the membrane surface.
      These observations are shedding some light on the previously observed selective
      disruption of cancerous cells induced by cationic compounds such as found in
      ionic liquids. 

PMID- 23881056
TI  - Insect-derived enzymes: a treasure for industrial biotechnology and food
      biotechnology.
AB  - Insects are the most diverse group of organisms on earth, colonizing almost every
      ecological niche of the planet. To survive in various and sometimes extreme
      habitats, insects have established diverse biological and chemical systems. Core
      components of these systems are enzymes that enable the insects to feed on
      diverse nutrient sources. The enzymes are produced by either the insects
      themselves (homologous) or by symbiotic organisms located in the insects' bodies
      or in their nests (heterologous). The use of these insect-associated enzymes for
      applications in the fields of food biotechnology and industrial (white)
      biotechnology is gaining more and more interest. Prominent examples of insect
      derived enzymes include peptidases, amylases, lipases, and beta-D-glucosidases.
      Highly potent peptidases for the degradation of gluten, a storage protein that
      can cause intestinal disorders, may be received from grain pests. Several
      insects, such as bark and ambrosia beetles and termites, are able to feed on
      wood. In the field of white biotechnology, their cellulolytic enzyme systems of
      mainly endo-1,4-beta-D-glucanases and beta-D-glucosidases can be employed for
      saccharification of the most prominent polymer on earth-cellulose.

PMID- 23881057
TI  - A systematic review of cancer GWAS and candidate gene meta-analyses reveals
      limited overlap but similar effect sizes.
AB  - Candidate gene and genome-wide association studies (GWAS) represent two
      complementary approaches to uncovering genetic contributions to common diseases.
      We systematically reviewed the contributions of these approaches to our knowledge
      of genetic associations with cancer risk by analyzing the data in the Cancer
      Genome-wide Association and Meta Analyses database (Cancer GAMAdb). The database
      catalogs studies published since January 1, 2000, by study and cancer type. In
      all, we found that meta-analyses and pooled analyses of candidate genes reported
      349 statistically significant associations and GWAS reported 269, for a total of
      577 unique associations. Only 41 (7.1%) associations were reported in both
      candidate gene meta-analyses and GWAS, usually with similar effect sizes. When
      considering only noteworthy associations (defined as those with false-positive
      report probabilities<=0.2) and accounting for indirect overlap, we found 202
      associations, with 27 of those appearing in both meta-analyses and GWAS. Our
      findings suggest that meta-analyses of well-conducted candidate gene studies may
      continue to add to our understanding of the genetic associations in the post-GWAS
      era.

PMID- 23881058
TI  - Clinical utility gene card for: Alagille Syndrome (ALGS).

PMID- 23881060
TI  - Earliest times before hip arthroplasty: from John Rhea Barton to Themistocles
      Gluck.
AB  - Over the last two centuries, treatment of hip pathology has evolved from joint
      excision and osteotomies to modern total hip arthroplasty (THA), which is
      considered one of the most successful surgical interventions ever developed. We
      here review the history of hip procedures that preceded Themistocles Gluck. This
      evaluation reminds us of the ephemeral nature of human industriousness and how
      medical research and procedures are not isolated developments but correlate to
      the social, economical, and cultural framework of their time. 

PMID- 23881059
TI  - A missense mutation in ALDH1A3 causes isolated microphthalmia/anophthalmia in
      nine individuals from an inbred Muslim kindred.
AB  - Nine affected individuals with isolated anophthalmia/microphthalmia from a large
      Muslim-inbred kindred were investigated. Assuming autosomal-recessive mode of
      inheritance, whole-genome linkage analysis, on DNA samples from four affected
      individuals, was undertaken. Homozygosity mapping techniques were employed and a
      1.5-Mbp region, homozygous in all affected individuals, was delineated. The
      region contained nine genes, one of which, aldehyde dehydrogenase 1 (ALDH1A3),
      was a clear candidate. This gene seems to encode a key enzyme in the formation of
      a retinoic-acid gradient along the dorsoventral axis during an early eye
      development and the development of the olfactory system. Sanger sequence analysis
      revealed a missense mutation, causing a substitution of valine (Val) to
      methionine (Met) at position 71. Analyzing the p.Val71Met missense mutation using
      standard open access software (MutationTaster online, PolyPhen, SIFT/PROVEAN)
      predicts this variant to be damaging. Enzymatic activity, studied in vitro,
      showed no changes between the mutated and the wild-type ALDH1A3 protein. 

PMID- 23881061
TI  - Humeral shaft fractures treated with antegrade intramedullary nailing: what are
      the consequences for the rotator cuff?
AB  - PURPOSE: The purpose of this study was to investigate the clinical and
      sonographic impact on the rotator cuff (RC) of the use of the anterolateral
      approach for nailing. METHODS: A retrospective cohort of 48 patients treated for
      humeral diaphyseal fractures at the University Hospital of Parma between 2007 and
      2011 was analysed. Inclusion criteria were (1) acute humeral shaft fractures
      treated with T2-proximal humeral nail (PHN) and (2) a minimum follow-up of one
      year. Exclusion criteria were (1) history of proximal and metaphyseal humeral
      fractures, (2) pathological fractures or open fractures of the humerus, and (3)
      RC lesions. Clinical assessment using the Constant score, simple shoulder test
      and through shoulder examination tests was carried out. The sonographic study
      investigated the integrity of the RC. RESULTS: Mean score on Constant's scale was
      78.21 points, with most patients achieving a good result (79% obtained more than
      65 points). One patient had a limited functional outcome (Constant's score of 49
      points). The sonographic findings described for supraspinatus tendon were a
      partial ruptures of less than 30 mm in three patients and a complete tendon
      rupture in one case. CONCLUSIONS: The results of this study suggest that the use
      of the anterolateral approach for antegrade humeral nailing ensures a good
      functional result with no significant clinical-sonographic impact on the rotator
      cuff and a satisfactory long term clinical outcome.

PMID- 23881062
TI  - Acetabular cup positioning in revision total hip arthroplasty with Paprosky type
      III acetabular defects: Martell radiographic analysis.
AB  - PURPOSE: This study evaluates acetabular cup position in the setting of revision
      total hip arthroplasty (THA) with severe acetabular bone defects. METHODS: With a
      definition of safe zone of abduction (30-50 degrees ) and anteversion (5-25
      degrees ), acetabular cup position was measured by a digital image analysis
      program for 34 patients with Paprosky type III acetabular bone defects. RESULTS:
      There were 24 cups (71%) for abduction and 26 cups (76%) for anteversion located
      in the safe zone. Nineteen cups (56%) were within the safe zone for both
      abduction and anteversion. There was no dislocation, however one cup out of the
      safe zone resulted in early cup failure due to aseptic loosening. CONCLUSIONS:
      The acetabular cup positioning in patients with Paprosky type III defects was
      'optimal' in half of the cases. The prevalence of optimal acetabular cup position
      was similar to those reported in primary THA, suggesting that the presence of a
      large acetabular bone defect may not be a significant risk factor for suboptimal
      acetabular cup positioning in the setting of revision THA.

PMID- 23881063
TI  - Simultaneous bilateral total hip arthroplasties do not lead to higher
      complication or allogeneic transfusion rates compared to unilateral procedures.
AB  - PURPOSE: About 20 % of patients undergoing a primary total hip arthroplasty could
      undergo a second contralateral procedure within five years. The possibility to
      perform simultaneous bilateral hip replacements instead of two-stage surgery
      could reduce hospitalisation time and patient management costs, but concerns
      exist because of risks related to massive blood loss and possible increase in
      complication rates. The purpose of this study is to assess the veracity of these
      concerns. METHODS: Parameters like blood loss, transfused blood units, total
      hospital length of stay (surgical and rehabilitation) and presence of in-hospital
      complications were collected from surgery reports of two different groups of
      patients. The first group comprised patients undergoing simultaneous bilateral
      total hip arthroplasty (n = 63), while the second group consisted of patients
      undergoing unilateral surgery (n = 97). Occurrence of complications within six
      post-operative months was assessed by phone interview. RESULTS: No differences
      were observed in complication, revision and mortality rates between the study
      groups. On the contrary, blood loss was significantly higher in the bilateral
      group, but the application of appropriate transfusion protocols reduced the use
      of allogeneic blood transfusion to the levels recorded for unilateral patients.
      Moreover, the difference in length of hospital stay (about two days) between the
      two groups was not clinically relevant. CONCLUSIONS: Our data show that
      simultaneous bilateral procedures do not lead to higher complication or
      allogeneic transfusion rates in comparison to unilateral hip replacement, and
      that, in cases of bilateral disease, they could significantly reduce the total
      length of hospital stay and, therefore, patient management costs.

PMID- 23881064
TI  - Benefits of small volume and small syringe for bone marrow aspirations of
      mesenchymal stem cells.
AB  - PURPOSE: Aspirating bone marrow from the iliac crest using small volumes of 1-4
      ml with a 10-ml syringe has been historically proposed for harvesting adult
      mesenchymal stem cells and described as a standard technique to avoid blood
      dilution. The disadvantage of repeated small aspirations is that there is a
      significantly increased time to harvest the bone marrow. However, it is not known
      if a large volume syringe can improve the rate of bone marrow aspiration without
      increasing blood dilution, thus reducing the quality of the aspirate. We compared
      the concentrations of mesenchymal stem cells obtained under normal conditions
      with two different size syringes. METHODS: Thirty adults (16 men and 14 women
      with a mean age of 49 +/- 14 years) underwent surgery with aspiration of bone
      marrow from their iliac crest. Bilateral aspirates were obtained from the iliac
      crest of the same patients with a 10-ml syringe and a 50-ml syringe. Cell
      analysis determined the frequencies of mesenchymal stem cells (as determined by
      the number of colonies) from each size of syringe. The cell count, progenitor
      cell concentration (colonies/ml marrow) and progenitor cell frequency (per
      million nucleated cells) were calculated. All bone marrow aspirates were
      harvested by the same surgeon. RESULTS: Aspirates of bone marrow demonstrated
      greater concentrations of mesenchymal stem cells with a 10-ml syringe compared
      with matched controls using a 50-ml syringe. Progenitor cell concentrations were
      on average 300 % higher using a 10-ml syringe than matched controls using a 50-ml
      syringe (p < 0.01). CONCLUSIONS: In normal human donors, bone marrow aspiration
      from 30 patients demonstrated a reduced mesenchymal stem cell number in aspirates
      obtained using a larger volume syringe (50 ml) as compared with a smaller volume
      syringe (10 ml).

PMID- 23881065
TI  - The pictogram of the pes planus from the first century AD.
AB  - PURPOSE: This study presents a pictogram engraved into the Marble Road of the
      ancient town of Ephesus, with a special emphasis on one part of it which
      represents a flat foot. Although the flat foot is a widespread and common
      disturbance in all time periods, we were motivated by a lack of its
      representation within iconographical, historical or other sources. METHOD: Aiming
      to confirm the diagnosis objectively we applied the modern diagnostic
      methodology, arch index (AI). The result was 0.33, which is a mathematical proof
      that the Ephesus foot is definitely flat. CONCLUSION: To the best of our
      knowledge, this picture from the first century AD is among the oldest
      representations of a flat foot in history.

PMID- 23881066
TI  - Classification of schizophrenia patients and healthy controls using p100 event
      related potentials for visual processing.
AB  - The study of event-related potentials (ERPs) is capable of elucidating the
      abnormalities in brain network dynamics relevant to the information-processing
      deficits in schizophrenia patients. In contrast to P50 and P300 ERPs, however,
      the results of P100 ERP studies in schizophrenia patients are less consistent. We
      have previously reported that P100 amplitudes did not differ significantly
      between patients with schizophrenia and healthy subjects. This result raised a
      question as to whether P100 ERPs carry information on brain network dynamics in
      schizophrenia patients that is distinct from normal controls. To answer this
      question, in this study we performed discrimination analysis on the P100 data.
      The rate of correct classification of patients and controls was high (80-90%
      depending on stimulus categories), indicating that patients have spatial patterns
      of P100 amplitudes that are distinguishable from those in healthy subjects. To
      further explore this possibility, we performed principal component analysis on
      the P100 data. For the patients, the first principal component represented global
      activity, the second component represented the reciprocal anterior-posterior
      activation, and the third component represented the hemispheric reciprocity in
      activity. The first and second components were similar to those of the control
      group; however, the third component in control subjects showed activation of the
      center versus anterior and posterior regions. This result is consistent with the
      notion of abnormalities in hemispheric asymmetries during the processing of
      sensory information in schizophrenia. In conclusion, this ERP study demonstrated
      that P100 amplitudes have information that can successfully classify patients and
      controls. 

PMID- 23881068
TI  - Mesenchymal stem cells in joint disease and repair.
AB  - Osteoarthritis (OA), a prevalent chronic condition with a striking impact on
      quality of life, represents an enormous societal burden that increases greatly as
      populations age. Yet no approved pharmacological intervention, biologic therapy
      or procedure prevents the progressive destruction of the OA joint. Mesenchymal
      stem cells (MSCs)-multipotent precursors of connective tissue cells that can be
      isolated from many adult tissues, including those of the diarthrodial joint-have
      emerged as a potential therapy. Endogenous MSCs contribute to maintenance of
      healthy tissues by acting as reservoirs of repair cells or as immunomodulatory
      sentinels to reduce inflammation. The onset of degenerative changes in the joint
      is associated with aberrant activity or depletion of these cell reservoirs,
      leading to loss of chondrogenic potential and preponderance of a fibrogenic
      phenotype. Local delivery of ex vivo cultures of MSCs has produced promising
      outcomes in preclinical models of joint disease. Mechanistically, paracrine
      signalling by MSCs might be more important than differentiation in stimulating
      repair responses; thus, paracrine factors must be assessed as measures of MSC
      therapeutic potency, to replace traditional assays based on cell-surface markers
      and differentiation. Several early-stage clinical trials, initiated or underway
      in 2013, are testing the delivery of MSCs as an intra-articular injection into
      the knee, but optimal dose and vehicle are yet to be established.

PMID- 23881070
TI  - Cam impingement of the hip: a risk factor for hip osteoarthritis.
AB  - Femoroacetabular impingement (FAI) is characterized by abnormal contact between
      the proximal femur and the acetabulum. Two subtypes have been described: pincer
      impingement, caused by an overcovered acetabulum; and cam impingement, which
      occurs as a result of an aspherical femoral head (cam abnormality). A strong
      correlation exists between cam impingement and the subsequent development of hip
      osteoarthritis (OA). Major cam abnormalities confer a high risk of OA. However,
      the association between cam abnormalities and the pathology of OA has been
      difficult to compare between studies, as different methods have been used to
      define the abnormality. Cam abnormalities are acquired during skeletal growth and
      could be influenced by high impact sporting activities. Preventative treatments
      aiming to reduce the incidence of cam abnormalities and subsequent OA could,
      therefore, be developed. In this Perspective, we discuss the current
      understanding of FAI, focusing on cam abnormalities and their association with
      OA.

PMID- 23881069
TI  - Advancing musculoskeletal research with nanoscience.
AB  - Nanoscience has arrived. Biological applications of nanoscience are particularly
      prominent and can be useful in a range of disciplines. Advances in nanoscience
      are underpinning breakthroughs in biomedical research and are beginning to be
      adopted by the rheumatology and musculoskeletal science communities. Within these
      fields, nanoscience can be applied to imaging, drug delivery, implant
      development, regenerative medicine, and the characterization of nanoscale
      features of cells, matrices and biomaterials. Nanoscience and nanotechnology also
      provide means by which the interaction of cells with their environment can be
      studied, thereby increasing the understanding of disease and regenerative
      processes. Although its potential is clear, nanoscience research tends to be
      highly technical, generally targeting an audience of physicists, chemists,
      materials scientists and engineers, and is difficult for a general audience to
      follow. This Review aims to step back from the most technical aspects of
      nanoscience and provide a widely accessible view of how it can be applied to
      advance the field of rheumatology, with an emphasis on technologies that can have
      an immediate impact on rheumatology and musculoskeletal research. 

PMID- 23881071
TI  - Vanadate-dependent bromoperoxidases from Ascophyllum nodosum in the synthesis of
      brominated phenols and pyrroles.
AB  - Bromoperoxidases from the brown alga Ascophyllum nodosum, abbreviated as
      V(Br)PO(AnI) and V(Br)PO(AnII), show 41% sequence homology and differ by a factor
      of two in the percentage of alpha-helical secondary structures. Protein monomers
      organize into homodimers for V(Br)PO(AnI) and hexamers for V(Br)PO(AnII).
      Bromoperoxidase II binds hydrogen peroxide and bromide by approximately one order
      of magnitude stronger than V(Br)PO(AnI). In oxidation catalysis, bromoperoxidases
      I and II turn over hydrogen peroxide and bromide similarly fast, yielding in
      morpholine-4-ethanesulfonic acid (MES)-buffered aqueous tert-butanol (pH 6.2)
      molecular bromine as reagent for electrophilic hydrocarbon bromination.
      Alternative compounds, such as tribromide and hypobromous acid are not
      sufficiently electrophilic for being directly involved in carbon-bromine bond
      formation. A decrease in electrophilicity from bromine via hypobromous acid to
      tribromide correlates in a frontier molecular orbital (FMO) analysis with larger
      energy gaps between the pi-type HOMO of, for example, an alkene and the
      sigma*(Br,X)-type LUMO of the bromination reagent. By using this approach, the
      reactivity of substrates and selectivity for carbon-bromine bond formation in
      reactions mediated by vanadate-dependent bromoperoxidases become predictable, as
      exemplified by the synthesis of bromopyrroles occurring naturally in marine
      sponges of the genera Agelas, Acanthella, and Axinella.

PMID- 23881072
TI  - Dietary flavonoid and lignan intake and mortality in a Spanish cohort.
AB  - BACKGROUND: Dietary flavonoids and lignans may protect against several chronic
      diseases, but there is little evidence on the relationship between flavonoid and
      lignan intake and mortality. We investigated the association between both all
      cause and specific-cause mortality and intake of flavonoids and lignans in the
      Spanish European Prospective Investigation into Cancer and Nutrition (EPIC-Spain)
      cohort. METHODS: The EPIC-Spain study follows 40,622 participants (38% men) aged
      29-69 years. A validated diet history questionnaire was administered at
      recruitment. A food composition database was compiled based on US Department of
      Agriculture and Phenol-Explorer databases. Cox proportional hazards models,
      adjusted for confounders, were used in the analyses. RESULTS: During a mean
      follow-up of 13.6 years, 1915 deaths were reported, with 416 from cardiovascular
      diseases (CVDs) and 956 from cancer. After adjustment for several potential
      confounders, the hazard ratios (HRs) for the highest versus the lowest quintile
      of dietary flavanone and flavonol intakes were 0.60 (95% confidence interval =
      0.38-0.94) and 0.59 (0.40-0.88). Total flavonoid intake was also associated with
      a decrease in all-cause mortality (0.71 [0.49-1.03]). Lignan intake was not
      associated with all-cause mortality. In cause-specific mortality analyses, using
      competing risk regressions, doubling total flavonoid intake was inversely related
      to mortality from CVD (HR for log2 0.87 [0.77-0.98]), but not to mortality from
      either cancer (HR for log2 0.96 [0.89-1.04]) or other causes (HR for log2 0.97
      [0.87-1.09]). CONCLUSIONS: A diet high in flavonoids, particularly in flavanones
      and flavonols, is associated with a reduction in all-cause mortality, mainly of
      mortality from CVD.

PMID- 23881074
TI  - Perceptual characteristics of nutritional supplements determine the expected
      effectiveness in boosting strength, endurance, and concentration performances.
AB  - The aim of this work was to examine the link between the physical-perceptual
      characteristics of nutritional supplements and their expected effectiveness in
      enhancing sport performance. Participants (n = 267) ranked nine images of fictive
      nutritional supplements, varying in shape, color, and route of administration
      (e.g., pill, powder, lotion, etc.), in ranked- order of expected effectiveness.
      They performed the task three times, (1) for strength, (2) endurance, and (3) for
      concentration. Results have revealed that the perceived effectiveness of the
      supplements was statistically significantly different for the three types of
      performances (p < .001). A significant interpersonal variability was observed in
      the ranking-order of the supplements. The findings reveal that perceptual
      characteristics of 'believed to be nutritional supplements', aimed at sport
      performance enhancement, influence their perceived effectiveness. Future
      inquiries in sport nutrition should examine the relationship between expected and
      experienced effectiveness of various nutritional supplements in enhancing sport
      performance.

PMID- 23881075
TI  - A weight off the mind: Clozapine and profound weight loss.

PMID- 23881076
TI  - Response to: 'quetiapine use: science or clever marketing?'.

PMID- 23881077
TI  - What is the importance and value of research on idiom comprehension in
      schizophrenia?

PMID- 23881078
TI  - Agomelatine-induced gynaecomastia.

PMID- 23881079
TI  - Use of quetiapine in child and adolescent populations - response to letter from
      Dr Lambe.

PMID- 23881080
TI  - Clozapine rechallenge following QTc prolongation.

PMID- 23881081
TI  - Scientific and ethical problems with risk assessment in clinical practice.

PMID- 23881082
TI  - A suggested classification for two groups of Campylobacter myoviruses.
AB  - Most Campylobacter bacteriophages isolated to date have long contractile tails
      and belong to the family Myoviridae. Based on their morphology, genome size and
      endonuclease restriction profile, Campylobacter phages were originally divided
      into three groups. The recent genome sequencing of seven virulent campylophages
      reveal further details of the relationships between these phages at the genome
      organization level. This article details the morphological and genomic features
      among the campylophages, investigates their taxonomic position, and proposes the
      creation of two new genera, the "Cp220likevirus" and "Cp8unalikevirus" within a
      proposed subfamily, the "Eucampyvirinae" 

PMID- 23881083
TI  - Nucleotide polymorphisms of the human papillomavirus 16 E1 gene.
AB  - The E1 ORF is one of the most conserved regions in the human papillomavirus (HPV)
      genome. The complete E1 gene of the HPV16 genome was amplified with four
      overlapping primer sets in 16 high-grade (CIN II, III) and 13 low-grade cervical
      (CIN I) intraepithelial neoplasias as well as in one cervical cancer case.
      Sequence analysis of the E6 and E7 genes was also carried out in the same
      cervical samples in order to confirm the association between nucleotide sequence
      variations in the HPV16 E1 ORF and HPV16 variant lineages. Analysis of the E1 ORF
      revealed 27 nucleotide changes, and these changes were correlated with those
      found in HPV16 Asian American and African type II variants. Of these nucleotide
      variations, A1668G, G2073A, T2169C, T2189C, A2453T, C2454T, A2587T and G2650A
      were identified only in high-grade dysplasia cases. A phylogenetic tree of the E1
      ORF and nucleotide sequence analysis of the E1, E6 and E7 genes revealed that
      intratypic nucleotide sequence polymorphisms located in the E1 ORF can be used to
      identify the major phylogenetic branch to which a HPV16 genome belongs. Moreover,
      amplification of the E1 ORF revealed a disruption between nucleotides 878 and
      1523 in five high- and two low-grade cervical cases, indicating that integration
      of HPV DNA occurs at an early stage of viral infection. 

PMID- 23881084
TI  - Genetic and evolutionary perspectives on genogroup III, genotype 2 bovine
      noroviruses.
AB  - Bovine noroviruses are enteric pathogens that are detected in stool samples from
      cattle. Five genogroups are currently described in the genus Norovirus (family
      Caliciviridae), and within the genogroups, sequences are further divided into
      genotypes according to genetic homology and phylogenetic relationships. In this
      study, stool specimens from Belgian cattle were screened by RT-PCR. All of the
      sequences that were detected were phylogenetically related to genogroup III
      genotype 2 bovine noroviruses, confirming their higher prevalence in comparison
      with strains from genotype 1. When other sequences from around the world were
      introduced, phylogenetic inferences allowed neither the determination of
      phylogenetic lineages over time nor the deduction of topotypes for genotype 2
      bovine noroviruses. Three complete genotype 2 bovine norovirus sequences were
      also compared genetically (Newbury2/1976 /UK, Dumfries/1994/UK and B309/2003/BE).
      Interestingly, the genetic divergence of the complete genomes of these three
      strains was relatively low, but a region of the N-terminal protein encoded by
      ORF1, the hypervariable region of the capsid gene encoded by ORF2, and a region
      of the minor structural protein encoded by ORF3 seem to be the most exposed to
      genetic evolution. Bayesian inference also showed that genetic evolution of
      genogroup III, genotype 2 bovine noroviruses over a 30-year period seemed to be
      lower than that already reported for noroviruses from the genotypes 3 and 4 in
      genogroup II. 

PMID- 23881085
TI  - Seasonality and prevalence of respiratory pathogens detected by multiplex PCR at
      a tertiary care medical center.
AB  - Respiratory tract infections (RTIs) are a leading cause of mortality and
      morbidity. Seasonality has been reported for many viruses, including influenza
      virus, respiratory syncytial virus (RSV), and the recently described human
      metapneumovirus (hMPV). We hypothesize that the availability of rapid, multiplex
      PCR diagnostics will provide better clinical care and new insights into the
      etiology and clinical spectrum of RTIs. We conducted a retrospective analysis of
      the incidence of respiratory pathogens at a 500-bed adult and 154-bed pediatric
      hospital tertiary care center. A total of 939 specimens from patients with an age
      range of 5 days to 91 years (median, 2 years) were tested by a multiplex
      respiratory pathogen PCR from November 14, 2011 to November 13, 2012. Sixty-five
      percent of specimens were positive for at least one pathogen. As the age of the
      patient increased, the positivity rate for the PCR decreased proportionately.
      Rhinoviruses/enteroviruses (Rhino/Entero) were the most prevalent (34.3 %)
      followed by RSV (19.2 %) and hMPV (6.2 %). Twelve percent of the positive samples
      were positive for multiple analytes, with Rhino/Entero and RSV being the most
      common combination. The peak months were September and May for Rhino/Entero
      infections, January for RSV and February for coronavirus. hMPV peaked 2 months
      after RSV, as has been observed recently in other studies. Multiplex PCR provides
      rapid diagnostic information that can be used to make knowledgeable clinical
      decisions and potentially reduce the use of antibiotics. Active respiratory PCR
      surveillance could also predict seasonal respiratory epidemics to allow for
      adequate planning of additional infection control measures. 

PMID- 23881087
TI  - Split cord malformation: experience from a tertiary referral center.
AB  - AIM: To present clinical, radiological, and follow-up features of 34 cases with
      spinal split cord malformation (SCM) treated in a tertiary referral center
      between April 2000 and March 2012. METHODS: A total of 59 patients were treated
      due to SCM between April 2000 and March 2012 at the Gazi University Faculty of
      Medicine, Division of Pediatric Neurosurgery. Data for each patient were
      evaluated retrospectively, and age, sex, clinical findings, radiological
      findings, complications, and surgical results were recorded. Patients with a
      follow-up period of less than 6 months, patients harboring an open spinal
      dysraphism, and patients who had had their index surgery in another clinic were
      excluded, thus leaving a total of 34 patients for further analysis. RESULTS:
      There were 19 females and 15 males ranging in age from 2 months to 15 years (mean
      5.04 years). In this cohort, skin stigma was the most common reason (76.5%) to
      seek medical care. Of the cases, 22 (64.7%) had lumbar SCM and 12 (35.3%) had
      thoracic SCM. There were no cervical SCM. Twenty-one (61.8%) of the cases had
      type 1 SCM and 13 (38.2%) had Type 2 SCM. Of the patients, 21 (61.8%) had a
      detectable neurological deficit at initial evaluation. There were no differences
      between patients with and without a neurological deficit regarding age, sex,
      type, and level of SCM. Overall evaluation of patients regarding their final
      neurological status revealed that 16 (47.1%) patients improved, 4 (11.8%)
      deteriorated, and 14 (41.2%) remained stable. CONCLUSIONS: In our opinion, all
      patients diagnosed with either type of SCM should be surgically treated to
      prevent further neurological deterioration. The results of this study, together
      with previously published data, confirm the effectiveness and safety of surgical
      intervention in SCM.

PMID- 23881088
TI  - Two-day hospital stay after laparoscopic colorectal surgery under an enhanced
      recovery after surgery (ERAS) pathway.
AB  - BACKGROUND: The present study aims to examine the feasibility and safety of a two
      day hospital stay after laparoscopic colorectal resection (LCR) under an enhanced
      recovery after surgery (ERAS) pathway. METHODS: Between 2003 and 2010, 882
      consecutive patients undergoing LCR were analyzed. Patients were grouped and
      analyzed according to whether their hospital stay was 2 days (group A) or longer
      (group B). Demographic, surgical, and postoperative data were compared. To
      identify independent predictive factors related to a short hospital stay, a
      multivariate analysis was also performed. RESULTS: Group A represented 10.3 % of
      this series (91 patients). There were no differences regarding age, gender, BMI,
      ASA, and previous abdominal surgeries between groups. Group A had a lower
      incidence of rectal cancer and anterior resections than group B (6.6 vs. 17.7 %
      [p = 0.006] and 14.3 vs. 23.4 % [p = 0.048]), respectively, and a lower mean
      operative time (170 min vs. 192 min; p = 0.002). Group A had a lower overall
      morbidity rate than group B (5.5 vs. 16.9 %; p = 0.004) and a lower incidence of
      surgery-related complications (5.5 vs. 14.9 %; p = 0.001). The overall conversion
      rate was 10 % (only one patient in group A required conversion), and the
      difference in conversion rate between groups was statistically significant (1.2
      vs. 10.7 %; p = 0.003). Group A had a lower readmission rate (0 vs. 4.9 %; p =
      0.089). Multivariate analysis showed that conversion, postoperative morbidity,
      and rectal prolapse were independently associated with the length of hospital
      stay. CONCLUSIONS: A two-day hospital stay after LCR is safe and feasible under
      an ERAS pathway, without compromising the readmission or complication rate.

PMID- 23881089
TI  - Spontaneous rectus sheath hematomas: when to restart anticoagulation?
AB  - BACKGROUND: The aim of the present study was to obtain data regarding the timing
      of anticoagulation resumption in patients with spontaneous rectus sheath
      hematomas (RSH). PATIENTS AND METHODS: The study is based on review of patients
      receiving anticoagulation medication who were diagnosed with a spontaneous RSH
      (traumatic and iatrogenic excluded) between 14 July 1997 and 17 March 2012.
      RESULTS: There were 156 patients (37 % male; aged 73 +/- 13 years) with an
      average body mass index of 29 +/- 7 (procedure group 28 +/- 6). Anticoagulants
      included coumadin (64 %), intravenous heparin (21 %), aspirin (8 %), and others
      (7 %). An intervention was needed in 29 (19 %) of the patients (5 % operative; 16
      % embolization). Sixty-two percent of patients had their anticoagulation
      restarted during their hospitalization, with a median re-initiation time of 4
      days after RSH diagnosis (range 2-8 days). Timing of anticoagulant resumption did
      not differ regardless of the need for intervention (3 vs. 4 days). The
      complication rate was 19 % (42 % in the procedure group, none specific to the
      procedure), with the most common being acute renal failure (n = 8; 5 %), death (n
      = 8; 5 %), and thrombotic events (n = 5; 3 %). After resumption of
      anticoagulation, two patients suffered enlargement of their RSH, both 2 days
      after resumption. CONCLUSIONS: Intervention to control hemorrhage was unnecessary
      in the majority of patients with RSH. In those with resumption of
      anticoagulation, the majority of patients were safely restarted by day 4. Even
      though complications secondary to anticoagulation were few, thrombotic
      complications outnumbered bleeding complications, suggesting that anticoagulation
      was withheld for too long after RSH diagnosis.

PMID- 23881090
TI  - Fabrication of volcano-shaped nano-patterned sapphire substrates using colloidal
      self-assembly and wet chemical etching.
AB  - Patterned sapphire substrates (PSS) have been widely used to enhance the light
      output power in GaN-based light emitting diodes. The shape and feature size of
      the pattern in a PSS affect its enhancement efficiency to a great degree. In this
      work we demonstrate the nanoscale fabrication of volcano-shaped PSS using a wet
      chemical etching approach in combination with a colloidal monolayer templating
      strategy. Detailed analysis by scanning electron microscopy reveals that the
      unique pattern shape is a result of the different corrosion-resistant abilities
      of silica masks of different effective heights during wet chemical etching. The
      formation of silica etching masks of different effective heights has been
      ascribed to the silica precursor solution in the interstice of the colloidal
      monolayer template being distributed unevenly after infiltration. In the
      subsequent wet chemical etching process, the active reaction sites altered as
      etching duration was prolonged, resulting in the formation of volcano-shaped nano
      patterned sapphire substrates. 

PMID- 23881091
TI  - Severe viral gastroenteritis in children after suboptimal rotavirus immunization
      in Taiwan.
AB  - BACKGROUND: The study aimed to investigate the molecular epidemiology of severe
      viral gastroenteritis (AGE) in children in Taiwan after the implementation of the
      rotavirus vaccine in the private sector. METHODS: Fecal samples from hospitalized
      children with severe AGE from April 2004 to March 2011 were examined by reverse
      transcription-polymerase chain reaction or polymerase chain reaction to identify
      enteric viral pathogens. The study period was divided to prevaccine (before
      September 2006) and postvaccine (after October 2006) periods. The prevalence of
      enteric viruses between the 2 periods was analyzed. The disease burdens of
      rotavirus- and norovirus-associated diseases were assessed according to vaccine
      implementation status and were adjusted for age. RESULTS: A total of 755 stool
      samples were collected from hospitalized patients with AGE; enteric viruses were
      identified in 586 patients (77.6%), including 44 with concomitant bacterial
      infection. Viral enteric infection by rotavirus, norovirus, astrovirus,
      sapovirus, enteric adenovirus, multiple viruses and bacterial coinfections were
      found in 216 (28.6%), 128 (17.0%), 24 (3.2%), 6 (0.8%), 69 (9.1 %), 99 (13.1%)
      and 44 (5.8%) patients, respectively. A significant increase of norovirus
      infection was found in the postvaccine period (P < 0.001); on the other hand,
      rotavirus infection in infants has been reduced substainally (P = 0.056) and the
      annual peak of rotavirus infection has gradually become less prominent, with a
      significant decline of coinfection of rotavirus with other pathogens.
      CONCLUSIONS: Suboptimal use of rotavirus vaccines in the private sector caused a
      slow but modest impact on severe rotavirus AGE, whereas norovirus infection
      became more common.

PMID- 23881092
TI  - Altered pre-reflective sense of agency in autism spectrum disorders as revealed
      by reduced intentional binding.
AB  - Autism spectrum disorders (ASDs) are neurodevelopmental conditions that severely
      affect social interaction, communication and several behavioural and cognitive
      functions, such as planning and monitoring motor actions. A renewed interest in
      intrapersonal cognition has recently emerged suggesting a putative dissociation
      between impaired declarative processes, such as autobiographical memory, and
      spared implicit processes, such as the sense of agency (SoA) in ASDs. However, so
      far only a few studies have investigated the integrity of SoA using tasks
      exclusively tapping reflective mechanisms. Since pre-reflective processes of SoA
      are based on the same predictive internal models that are involved in planning
      and monitoring actions, we hypothesized that pre-reflective aspects of SoA, as
      measured by the intentional binding effect, would be altered in adults with high
      functioning autism spectrum disorders, relative to volunteers with typical
      development. Here, in accordance with our hypothesis, we report reduced IB in
      participants with ASDs. 

PMID- 23881093
TI  - Brief report: autism awareness: views from a campus community.
AB  - This paper reports on a college community's views of the diagnostic
      characteristics and causes associated with autism spectrum disorders. An
      anonymous on-line survey of autism knowledge was distributed via campus server
      university-wide to all undergraduates, graduate students, faculty, and staff. Of
      the 1,057 surveys completed, 76 % of respondents had more correct answers than
      neutral and incorrect ones. Respondents who reported that they or someone in
      their immediate family had autism had significantly more correct responses than
      other respondents. Demographic variables of respondent sex, age, education, and
      role at the university independently accounted for significant, though modest,
      variance in autism knowledge. More accurate and widespread dissemination of
      information about autism may facilitate a smoother transition for college
      students who are on the spectrum. 

PMID- 23881094
TI  - Maternal parenting behavior and child behavior problems in families of children
      and adolescents with autism spectrum disorder.
AB  - Parents of a child with autism spectrum disorder (ASD) face specific challenges
      in parenting, but concrete parenting behavior has never been properly
      investigated in these families. This exploratory questionnaire study compared
      parenting behaviors among mothers of children and adolescents with ASD (n = 552)
      and without ASD (n = 437) and examined associations between child behavior
      problems and parenting behavior. Results showed that mothers of children with ASD
      reported significantly lower scores on Rules and Discipline and higher scores on
      Positive Parenting, Stimulating the Development, and Adapting the Environment.
      Age was differently related to parenting behavior in the ASD versus control
      group. Furthermore, distinctive correlation patterns between parenting behavior
      and externalizing or internalizing behavior problems were found for both groups.

PMID- 23881095
TI  - Finding non-crystallographic symmetry in density maps of macromolecular
      structures.
AB  - The internal symmetry of a macromolecule is both an important aspect of its
      function and a useful feature in obtaining a structure by X-ray crystallography
      and other techniques. A method is presented for finding internal symmetry and
      other non-crystallographic symmetry in a structure based on patterns of density
      in a density map for that structure. Regions in map that are similar are
      identified by cutting out a sphere of density from a region that has high local
      variation and using an FFT-based correlation search to find other regions that
      match. The relationships among correlated regions are then refined to maximize
      their correlations and are found to accurately represent non-crystallographic
      symmetry in the map. 

PMID- 23881096
TI  - Neuropsychological correlates of transcription factor AP-2Beta, and its
      interaction with COMT and MAOA in healthy females.
AB  - BACKGROUND: The transcription factor AP-2beta has been shown to impact clinical
      and neuropsychological properties. Apparently, it regulates the transcription of
      genes that code for molecules which are part of the catecholaminergic
      transmission system. This investigation focuses on possible effects of the
      transcription factor AP-2beta intron 2 polymorphism on cognitive performance
      parameters. METHODS: This hypothesis-driven investigation examined the effects
      and interactions of the transcription factor AP-2beta intron 2 polymorphism, the
      Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable
      number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive
      performance parameters within a group of 200 healthy women (age: mean +/- SD,
      23.93 +/- 3.33 years). RESULTS: The AP-2beta polymorphism significantly
      influenced cognitive performance (in particular, the Trail Making Test part B),
      whereas the MAOA and COMT polymorphisms did not. However, there was an
      interaction effect of the AP-2beta * MAOA * COMT genotypes on the decision bias
      beta of the degraded-stimulus version of the continuous performance task. Only
      the Val158Met COMT polymorphism showed an influence on personality questionnaires
      (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and
      Character Inventory). CONCLUSION: The transcription factor AP-2beta intron 2
      polymorphism had more influence on cognition than the MAOA and COMT
      polymorphisms. Possibly, the AP-2beta genotype might influence cognition through
      pathways other than those that regulate MAOA and COMT transcription. Interactions
      of transcription factor AP-2beta, COMT, and MAOA polymorphisms suggest higher
      leverage effects of transcription factor AP-2beta in subjects with high dopamine
      availability.

PMID- 23881097
TI  - Neuronal carbonic anhydrase VII provides GABAergic excitatory drive to exacerbate
      febrile seizures.
AB  - Brain carbonic anhydrases (CAs) are known to modulate neuronal signalling. Using
      a novel CA VII (Car7) knockout (KO) mouse as well as a CA II (Car2) KO and a CA
      II/VII double KO, we show that mature hippocampal pyramidal neurons are endowed
      with two cytosolic isoforms. CA VII is predominantly expressed by neurons
      starting around postnatal day 10 (P10). The ubiquitous isoform II is expressed in
      neurons at P20. Both isoforms enhance bicarbonate-driven GABAergic excitation
      during intense GABAA-receptor activation. P13-14 CA VII KO mice show behavioural
      manifestations atypical of experimental febrile seizures (eFS) and a complete
      absence of electrographic seizures. A low dose of diazepam promotes eFS in P13
      P14 rat pups, whereas seizures are blocked at higher concentrations that suppress
      breathing. Thus, the respiratory alkalosis-dependent eFS are exacerbated by
      GABAergic excitation. We found that CA VII mRNA is expressed in the human
      cerebral cortex before the age when febrile seizures (FS) occur in children. Our
      data indicate that CA VII is a key molecule in age-dependent neuronal pH
      regulation with consequent effects on generation of FS. 

PMID- 23881098
TI  - A cyclic GMP-dependent signalling pathway regulates bacterial phytopathogenesis.
AB  - Cyclic guanosine 3',5'-monophosphate (cyclic GMP) is a second messenger whose
      role in bacterial signalling is poorly understood. A genetic screen in the plant
      pathogen Xanthomonas campestris (Xcc) identified that XC_0250, which encodes a
      protein with a class III nucleotidyl cyclase domain, is required for cyclic GMP
      synthesis. Purified XC_0250 was active in cyclic GMP synthesis in vitro. The
      linked gene XC_0249 encodes a protein with a cyclic mononucleotide-binding (cNMP)
      domain and a GGDEF diguanylate cyclase domain. The activity of XC_0249 in cyclic
      di-GMP synthesis was enhanced by addition of cyclic GMP. The isolated cNMP domain
      of XC_0249 bound cyclic GMP and a structure-function analysis, directed by
      determination of the crystal structure of the holo-complex, demonstrated the site
      of cyclic GMP binding that modulates cyclic di-GMP synthesis. Mutation of either
      XC_0250 or XC_0249 led to a reduced virulence to plants and reduced biofilm
      formation in vitro. These findings describe a regulatory pathway in which cyclic
      GMP regulates virulence and biofilm formation through interaction with a novel
      effector that directly links cyclic GMP and cyclic di-GMP signalling. 

PMID- 23881099
TI  - MAP1B-dependent Rac activation is required for AMPA receptor endocytosis during
      long-term depression.
AB  - The microtubule-associated protein 1B (MAP1B) plays critical roles in neurite
      growth and synapse maturation during brain development. This protein is well
      expressed in the adult brain. However, its function in mature neurons remains
      unknown. We have used a genetically modified mouse model and shRNA techniques to
      assess the role of MAP1B at established synapses, bypassing MAP1B functions
      during neuronal development. Under these conditions, we found that MAP1B
      deficiency alters synaptic plasticity by specifically impairing long-term
      depression (LTD) expression. Interestingly, this is due to a failure to trigger
      AMPA receptor endocytosis and spine shrinkage during LTD. These defects are
      accompanied by an impaired targeting of the Rac1 activator Tiam1 at synaptic
      compartments. Accordingly, LTD and AMPA receptor endocytosis are restored in
      MAP1B-deficient neurons by providing additional Rac1. Therefore, these results
      indicate that the MAP1B-Tiam1-Rac1 relay is essential for spine structural
      plasticity and removal of AMPA receptors from synapses during LTD. This work
      highlights the importance of MAPs as signalling hubs controlling the actin
      cytoskeleton and receptor trafficking during plasticity in mature neurons. 

PMID- 23881100
TI  - A new diagnostic test for endometrial cancer?: Cytology analysis of
      sonohysterography distention media.
AB  - OBJECTIVE: During saline-infused sonohysterography (SIS), the distension fluid is
      typically discarded. If cytology analysis could identify those patients with
      endometrial cancer, many women would be spared from further procedures. METHODS:
      Thirty consecutive patients with clinical stage I or II endometrial
      adenocarcinoma were prospectively recruited preoperatively. Saline-infused
      sonohysterography was performed by instilling 5 mL of saline, withdrawing and
      sending for analysis. Saline was reinfused until complete SIS images were
      obtained and sent separately for cytology. RESULTS: Of the 30 women enrolled, SIS
      was technically successful in 29. Demographics included mean age (60.5 +/- 6.99
      years), body mass index (35.55 +/- 8.18 kg/m), endometrioid histology (76%), and
      grade (grade 1, 67%). Prestudy diagnostic method included biopsy (70%),
      dilatation and curettage (17%), and hysteroscopy (10%). Adequate cytology
      specimens were obtained in 66% of the 5 mL flushes and 72% of the complete SIS
      collections. Of adequate specimens, the sensitivities to detect endometrial
      cancer for the 5-mL, complete, and combined fluid samples were 26% (95%
      confidence interval, 9%-51%), 36% (17%-59%), and 42% (22%-63%). Sensitivity based
      on the whole study sample (N = 30) was 33% (17%-53%). Statistical significance
      was not found in the association between a positive test and age, body mass
      index, grade, diagnostic method, or volume instilled or aspirated. CONCLUSIONS:
      Most patients with early endometrial cancer can undergo SIS procedures with
      adequate cytology specimens obtained from distention media. However, the
      sensitivity is low, and refinements are necessary before utilizing as a
      diagnostic test. In cases with positive results, the patient may be able to avoid
      other costly and painful procedures.

PMID- 23881101
TI  - Is neoadjuvant chemotherapy followed by radical surgery more effective than
      radiation therapy for stage IIB cervical cancer?
AB  - OBJECTIVE: The primary objective of the study was to compare the survival rate of
      patients who had received neoadjuvant chemotherapy with that of patients who had
      received radiation therapy for stage IIB cervical cancer. The secondary objective
      was to analyze the effect of neoadjuvant chemotherapy on pathological prognostic
      factors. MATERIALS AND METHODS: We retrospectively reviewed the medical records
      of patients who had received therapy for stage IIB cervical cancer. Based on the
      primary therapy, 192 patients were divided into 2 groups; patients in the
      neoadjuvant chemotherapy group (n =103) underwent a type III radical hysterectomy
      after completion of the neoadjuvant chemotherapy. Patients in the other group (n
      = 89) were treated with radiation alone or a combination of chemotherapy and
      radiotherapy. RESULTS: After neoadjuvant chemotherapy, the level of squamous cell
      carcinoma antigen, tumor size, lymph node involvement, and parametrium
      involvement were significantly decreased. However, 90.3% of the patients who had
      received neoadjuvant chemotherapy needed to have adjuvant therapy after radical
      surgery because of poor pathological prognostic factors. The rate of disease-free
      survival did not differ significantly between the 2 groups. However, the overall
      survival rate was significantly lower in the neoadjuvant chemotherapy group for
      patients who were 60 years or older (P = 0.03). The rates of disease-free
      survival and overall survival for patients who had a good (complete or partial)
      response to the neoadjuvant chemotherapy were not significantly higher than the
      rates for patients in the radiation therapy group. CONCLUSIONS: Although
      neoadjuvant chemotherapy improved pathological prognostic factors in patients
      with stage IIB cervical cancer, it was not sufficiently effective to decrease
      adjuvant therapy. Neoadjuvant chemotherapy also did not improve the rate of
      patient survival compared to the rate of patient survival in the radiation
      therapy group.

PMID- 23881102
TI  - Health care use among endometrial cancer survivors: a study from PROFILES, a
      population-based survivorship registry.
AB  - OBJECTIVE: Increasing numbers of endometrial cancer survivors place a high burden
      on the health care system. This study describes the number of visits to the
      general practitioner, the medical specialist and other care services, compared
      with the general population, and factors associated with this health care use:
      age, marital status, education, body mass index, comorbidity, years since
      diagnosis, and radiotherapy. METHODS: Survivors of stage I to stage II
      endometrial cancer diagnosed between 1999 and 2007 were selected from the
      Eindhoven Cancer Registry. Survivors (N = 742) completed a questionnaire about
      their demographic characteristics and health care use. Cancer-related information
      was retrieved from the Eindhoven Cancer Registry. RESULTS: Endometrial cancer
      survivors visited their medical specialist more often (3.4 times per year) than
      the general population. In relation to their cancer, they visited their general
      practitioner once and their medical specialist twice per year. Use of additional
      care services was low (14%) but higher among younger survivors (33%). Younger
      women were more likely to make cancer-related visits to their general
      practitioner, whereas more highly educated women were less likely to visit their
      general practitioner and more likely to make cancer-related medical specialist
      visits. Women with more comorbid conditions were more likely to make general and
      cancer-related general practitioner visits. Radiotherapy and body mass index were
      not related to health care use. CONCLUSIONS: Endometrial cancer survivors use
      more health care than women in the general population. Younger women visit their
      general practitioner more often in relation to their cancer and use more
      additional care services. More highly educated survivors were more likely to
      visit a medical specialist in relation to their cancer.

PMID- 23881103
TI  - Circadian fluctuations in onset of perimesencephalic hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) occurs more often during working hours
      and in the evening, and thus at times of relatively high blood pressure, with an
      even distribution over the days of the week in most studies. Perimesencephalic
      hemorrhage (PMH) is a non-aneurysmal subset of subarachnoid hemorrhage (SAH)
      without known circadian fluctuation. We studied the time and day of onset in a
      large series of patients with PMH. For all 249 PMH patients included in our SAH
      database we analyzed the time (categorized in 2- and 6-h intervals) and day of
      onset by calculating rate ratios (RRs) with corresponding 95 % confidence
      intervals (CIs) for time and day, with the afternoon and Saturday as reference.
      The risk of PMH was lower between 2-4 AM (RR 0.14; 95 % CI 0.03-0.63), 4-6 AM (RR
      0.21; 95 % CI 0.06-0.75) and 6-8 AM (RR 0.07; 95 % CI 0.01-0.54). A tendency
      towards higher risks in the morning and afternoon was observed. Analyzing the
      time of onset in 6-h intervals also showed a lower risk (RR 0.35; 95 % CI 0.21
      0.58) during night hours (12-6 AM). The risk of PMH was evenly distributed over
      the days of the week. PMH occurs less often during night hours. The pattern of
      PMH during the day shows similarities to that seen in aSAH, although the
      differences over the day are not statistically significant, as they are in aSAH.
      The occurrence of PMH is evenly distributed over the days of the week, as it is
      in aSAH.

PMID- 23881104
TI  - Hereditary neuropathy with liability to pressure palsy: fulminant radicular
      dysfunction during anterolateral lumbar interbody fusion.

PMID- 23881105
TI  - Exome sequencing expands the mutational spectrum of SPG8 in a family with
      spasticity responsive to L-DOPA treatment.

PMID- 23881106
TI  - Diaphragm of the internal carotid artery: a novel cause of pulsatile tinnitus.

PMID- 23881107
TI  - Heterozygous TREX1 mutations in early-onset cerebrovascular disease.

PMID- 23881108
TI  - Modulation of polyamine metabolic flux in adipose tissue alters the accumulation
      of body fat by affecting glucose homeostasis.
AB  - The continued rise in obesity despite public education, awareness and policies
      indicates the need for mechanism-based therapeutic approaches to help control the
      disease. Our data, in conjunction with other studies, suggest an unexpected role
      for the polyamine catabolic enzyme spermidine/spermine-N1-acetyltransferase
      (SSAT) in fat homeostasis. Our previous studies showed that deletion of SSAT
      greatly exaggerates weight gain and that the transgenic overexpression suppresses
      weight gain in mice on a high-fat diet. This discovery is substantial but the
      underlying molecular linkages are only vaguely understood. Here, we used a
      comprehensive systems biology approach, on white adipose tissue (WAT), to
      discover that the partition of acetyl-CoA towards polyamine catabolism alters
      glucose homeostasis and hence, fat accumulation. Comparative proteomics and
      antibody-based expression studies of WAT in SSAT knockout, wild type and
      transgenic mice identified nine proteins with an increasing gradient across the
      genotypes, all of which correlate with acetyl-CoA consumption in polyamine
      acetylation. Adipose-specific SSAT knockout mice and global SSAT knockout mice on
      a high-fat diet exhibited similar growth curves and proteomic patterns in their
      WAT, confirming that attenuated consumption of acetyl-CoA in acetylation of
      polyamines in adipose tissue drives the obese phenotype of these mice. Analysis
      of protein expression indicated that the identified changes in the levels of
      proteins regulating acetyl-CoA consumption occur via the AMP-activated protein
      kinase pathway. Together, our data suggest that differential expression of SSAT
      markedly alters acetyl-CoA levels, which in turn trigger a global shift in
      glucose metabolism in adipose tissue, thus affecting the accumulation of body
      fat. 

PMID- 23881109
TI  - Suicides by jumping from a height in Hong Kong: a review of coroner court files.
AB  - PURPOSE: Jumping from a height is the most common method for suicide in Hong Kong
      and other urban cities, but it remains understudied locally and internationally.
      We used Coroner records in exploring the ecological factors associated with these
      deaths and the personal characteristics of persons who jumped to their death
      (hereafter, "jumping suicides"). We compared suicides by jumping with all other
      suicides and examined the suicides that occurred at ten different jumping sites.
      METHODS: The Coroner's files of all suicides in Hong Kong from 2002 to 2007
      included 6,125 documented deaths. RESULTS: 2,964 (48.4%) involved jumping during
      the study period. Eighty-three percent (83%) of suicide jumps occurred in
      residential buildings, and of these, 61% occurred from the decedent's own home.
      Jumping suicides differed from non-jumping suicides in terms of their socio
      demographic characteristics (e.g., for male: 60.8 vs. 67.3% of jumping suicide
      and non-jumping suicides, p < 0.0001) and the presence of physical illness (44.4
      vs. 42.7% for jumping and non-jumping suicides, p < 0.0001). While statistically
      significant, these differences are relatively modest. In contrast, 40.7
      documented illnesses vs. 23.1% for jumping and non-jumping suicides (p < 0.0001).
      CONCLUSIONS: Means restriction is a key strategy for suicide prevention.
      Installation of physical barriers, one of the mean restriction strategies, at
      common places for suicide has strong evidence to avert suicides without
      substitution effects. There seems to be challenges to implement physical barriers
      to prevent residential jumping suicides. Simply applying physical barriers to
      preclude jumping in Hong Kong appears to be difficult given its ubiquitous "high
      rise" residential dwellings. Hence, we also need to develop alternative
      strategies aimed at preventing people from becoming suicidal.

PMID- 23881110
TI  - Abca3 haploinsufficiency is a risk factor for lung injury induced by hyperoxia or
      mechanical ventilation in a murine model.
AB  - BACKGROUND: Heterozygous ATP-binding-cassette subfamily A member 3 (ABCA3)
      mutations are associated with neonatal respiratory complications. In an adult
      murine model, we investigated whether Abca3 haploinsufficiency is a predisposing
      factor for lung injury induced by hyperoxia or mechanical ventilation. METHODS:
      Abca3 haploinsufficient (Abca3(+/-)) and wild-type (WT) mice were prospectively
      randomized to 25 min of ventilation or 72 h of hyperoxia or left unchallenged in
      air. RESULTS: As compared with WT mice, unchallenged Abca3(+/-) mice had
      significantly decreased lung phosphatidylcholine (PC) and phosphatidylglycerol
      (PG) levels (P < 0.02) and decreased lung compliance (P < 0.05). When ventilated
      for 25 min, Abca3(+/-) mice demonstrated a significantly greater increase in
      bronchoalveolar lavage (BAL) interleukins (P <= 0.01) and lung wet to dry ratio
      (P < 0.005). Hyperoxia resulted in increased compliance (P < 0.05) and total lung
      capacity (TLC) (P = 0.01) only in the Abca3(+/-) mice, consistent with enlarged
      alveolar spaces. The ratio of PC to PG in BAL-relevant for surfactant dysfunction
      was significantly elevated by oxygen exposure, with the greatest increase in
      Abca3(+/-) mice. CONCLUSION: In a murine model, Abca3 haploinsufficiency results
      in an altered biochemical and lung mechanical phenotype, as well as a greater
      lung injury induced by hyperoxia or mechanical ventilation. The inability to
      maintain a normal PC/PG ratio appears to play a key role.

PMID- 23881111
TI  - Head impact exposure in youth football: elementary school ages 9-12 years and the
      effect of practice structure.
AB  - Head impact exposure in youth football has not been well-documented, despite
      children under the age of 14 accounting for 70% of all football players in the
      United States. The objective of this study was to quantify the head impact
      exposure of youth football players, age 9-12, for all practices and games over
      the course of single season. A total of 50 players (age = 11.0 +/- 1.1 years) on
      three teams were equipped with helmet mounted accelerometer arrays, which
      monitored each impact players sustained during practices and games. During the
      season, 11,978 impacts were recorded for this age group. Players averaged 240 +/-
      147 impacts for the season with linear and rotational 95th percentile magnitudes
      of 43 +/- 7 g and 2034 +/- 361 rad/s(2). Overall, practice and game sessions
      involved similar impact frequencies and magnitudes. One of the three teams
      however, had substantially fewer impacts per practice and lower 95th percentile
      magnitudes in practices due to a concerted effort to limit contact in practices.
      The same team also participated in fewer practices, further reducing the number
      of impacts each player experienced in practice. Head impact exposures in games
      showed no statistical difference. While the acceleration magnitudes among 9-12
      year old players tended to be lower than those reported for older players, some
      recorded high magnitude impacts were similar to those seen at the high school and
      college level. Head impact exposure in youth football may be appreciably reduced
      by limiting contact in practices. Further research is required to assess whether
      such a reduction in head impact exposure will result in a reduction in concussion
      incidence.

PMID- 23881113
TI  - A universal value of effective annealing time for rapid oxide nucleation and
      growth under pulsed ultraviolet laser irradiation.
AB  - The effective annealing times (t(eff)) for nucleating various oxides from an
      amorphous matrix under nanosecond pulsed laser irradiation have been determined.
      The oxides, which had perovskite, bixbyite, anatase, and pyrochlore structures,
      showed similar t(eff) values for crystal nucleation of around 60 ns. This
      indicates that the effective annealing time is a good universal value for
      evaluating pulsed laser-induced oxide nucleation. Time-resolved resistance
      measurements of tin-doped In2O3 thin films under pulsed laser irradiation showed
      that crystal nucleation and rapid growth proceeded spontaneously with an
      instantaneous temperature rise.

PMID- 23881116
TI  - Standardized versus customized high-intensity training: effects on cycling
      performance.
AB  - PURPOSE: To determine whether a submaximal cycling test could be used to monitor
      and prescribe high-intensity interval training (HIT). METHODS: Two groups of male
      cyclists completed 4 HIT sessions over a 2-wk period. The structured-training
      group (SG; n = 8, VO2max = 58.4 +/- 4.2 mL . min-1 . kg-1) followed a
      predetermined training program while the flexible-training group (FG; n = 7,
      VO2max = 53.9 +/- 5.0 mL . min-1 . kg-1) had the timing of their HIT sessions
      prescribed based on the data of the Lamberts and Lambert Submaximal Cycle Test
      (LSCT). RESULTS: Effect-size calculations showed large differences in the
      improvements in 40-km time-trial performance after the HIT training between SG (8
      +/- 45 s) and FG (48 +/- 42 s). Heart-rate recovery, monitored during the study,
      tended to increase in FG and remain unchanged in SG. CONCLUSIONS: The results of
      the current study suggest that the LSCT may be a useful tool for coaches to
      monitor and prescribe HIT.

PMID- 23881118
TI  - Interstitial lung disease due to fumes from heat-cutting polymer rope.
AB  - Interstitial lung disease (ILD) due to inhalation of fume/smoke from heating or
      burning of synthetic polymers has not been reported previously. A fish farm
      worker developed ILD after cutting rope (polypropylene and nylon) for about 2
      hours per day over an extended period using an electrically heated 'knife'. This
      process produced fume/smoke that entered the workers breathing zone. No other
      likely cause was identified. This case suggests that exposure to airborne
      contaminants generated by the heating or burning of synthetic polymers has the
      potential to cause serious lung disease. 

PMID- 23881112
TI  - PEG-maleimide hydrogels for protein and cell delivery in regenerative medicine.
AB  - Protein- and cell-based therapies represent highly promising strategies for
      regenerative medicine, immunotherapy, and oncology. However, these therapies are
      significantly limited by delivery considerations, particularly in terms of
      protein stability and dosing kinetics as well as cell survival, engraftment, and
      function. Hydrogels represent versatile and robust delivery vehicles for proteins
      and cells due to their high water content that retains protein biological
      activity, high cytocompatibility and minimal adverse host reactions, flexibility
      and tunability in terms of chemistry, structure, and polymerization format,
      ability to incorporate various biomolecules to convey biofunctionality, and
      opportunity for minimally invasive delivery as injectable carriers. This review
      highlights recent progress in the engineering of poly(ethylene glycol) hydrogels
      cross-linked using maleimide reactive groups for protein and cell delivery. 

PMID- 23881119
TI  - Staff happiness and work satisfaction in a tertiary psychiatric centre.
AB  - BACKGROUND: Mental health professionals are at a high risk of burnout. Positive
      psychology outcomes of staff in acute in-patient psychiatric wards are poorly
      researched and unclear. AIMS: To quantify the satisfaction with life and work
      life satisfaction of mental health staff at a large university-affiliated
      tertiary psychiatric centre. METHODS: We utilized the Satisfaction with Life
      Scale (SWLS) and the Work-Life Satisfaction Questionnaire (WLSQ). RESULTS: Two
      hundred and nine out of 450 staff members (46%) participated; mean age 48.2 + 9.9
      years; 63% were male. On average the participants had been practising their
      speciality for 21.1 + 9.8 years (range: 2-48). The mean total SWLS scores
      differed significantly between professions (P < 0.05). The highest levels of
      happiness were reported by psychologists and social workers, followed by the
      administrative staff, the psychiatrists and finally the nursing staff. Staff
      scored the highest for work as a 'calling' followed by work as a 'career' and the
      lowest rating for work as a 'job'. The mean total WLSQ score differed between
      professions, (P < 0.01). The highest levels of work as a calling were reported by
      psychiatrists (mean 2.87 of possible 5.0), followed by psychologists and social
      workers, nursing staff and finally administrative staff. CONCLUSIONS:
      Satisfaction with life and work orientation do not correlate among mental health
      professionals. Although highly motivated and perceiving psychiatry as a 'calling'
      psychiatrists score low on levels of satisfaction with life. Improving staff
      happiness may contribute to increase in moral and counter burnout.

PMID- 23881120
TI  - A review of guidelines for collaboration in substance misuse management.
AB  - BACKGROUND: Substance misuse among the working population results in increasing
      economic costs. General practitioners (GPs) and occupational physicians (OPs) can
      play a central role in detecting and managing substance misuse in the working
      population. Their collaboration could be critical in coordinating care, in
      facilitating rehabilitation and in reducing sickness absence. AIMS: To search
      guidelines for evidence on collaboration between GPs and OPs in substance misuse
      detection and management in the working population. METHODS: International
      guidelines regarding collaborative care for alcohol, illicit drug, hypnotic and
      tranquillizer misuse were identified by a systematic search in the Guidelines
      International Network and US National Guidelines Clearinghouse databases.
      RESULTS: In total, 20 guidelines were considered of sufficient methodological
      quality, based on the criteria of the Appraisal of Guidelines for Research and
      Education II instrument. Only two guidelines reported on the OP's role in
      screening and intervention for alcohol misuse. CONCLUSIONS: There is a lack of
      guidance on the OP's role and on collaboration between GPs and OPs in this field.
      Further study is required on their respective roles in substance misuse
      management, the effectiveness of workplace interventions and the benefits of
      collaboration.

PMID- 23881122
TI  - Data communications using guided elastic waves by time reversal pulse position
      modulation: experimental study.
AB  - In this paper, we present and demonstrate a low complexity elastic wave signaling
      and reception method to achieve high data rate communication on dispersive solid
      elastic media, such as metal pipes, using piezoelectric transducers of PZT (lead
      zirconate titanate). Data communication is realized using pulse position
      modulation (PPM) as the signaling method and the elastic medium as the
      communication channel. The communication system first transmits a small number of
      training pulses to probe the dispersive medium. The time-reversed probe signals
      are then utilized as the information carrying waveforms. Rapid timing acquisition
      of transmitted waveforms for demodulation over elastic medium is made possible by
      exploring the reciprocity property of guided elastic waves. The experimental
      tests were conducted using a National Instrument PXI system for waveform
      excitation and data acquisition. Data telemetry bit rates of 10 kbps, 20 kbps, 50
      kbps and 100 kbps with the average bit error rates of 0, 5.75 * 10(-4), 1.09 *
      10(-2) and 5.01 * 10(-2), respectively, out of a total of 40, 000 transmitted
      bits were obtained when transmitting at the center frequency of 250 kHz and a 500
      kHz bandwidth on steel pipe specimens. To emphasize the influence of time
      reversal, no complex processing techniques, such as adaptive channel equalization
      or error correction coding, were employed.

PMID- 23881123
TI  - Development of a wireless displacement measurement system using acceleration
      responses.
AB  - Displacement measurements are useful information for various engineering
      applications such as structural health monitoring (SHM), earthquake engineering
      and system identification. Most existing displacement measurement methods are
      costly, labor-intensive, and have difficulties particularly when applying to full
      scale civil structures because the methods require stationary reference points.
      Indirect estimation methods converting acceleration to displacement can be a good
      alternative as acceleration transducers are generally cost-effective, easy to
      install, and have low noise. However, the application of acceleration-based
      methods to full-scale civil structures such as long span bridges is challenging
      due to the need to install cables to connect the sensors to a base station. This
      article proposes a low-cost wireless displacement measurement system using
      acceleration. Developed with smart sensors that are low-cost, wireless, and
      capable of on-board computation, the wireless displacement measurement system has
      significant potential to impact many applications that need displacement
      information at multiple locations of a structure. The system implements an FIR
      filter type displacement estimation algorithm that can remove low frequency
      drifts typically caused by numerical integration of discrete acceleration
      signals. To verify the accuracy and feasibility of the proposed system,
      laboratory tests are carried out using a shaking table and on a three storey
      shear building model, experimentally confirming the effectiveness of the proposed
      system. 

PMID- 23881124
TI  - Hydrogen sensing with Ni-doped TiO2 nanotubes.
AB  - Doping with other elements is one of the efficient ways to modify the physical
      and chemical properties of TiO2 nanomaterials. In the present work, Ni-doped TiO2
      nanotubes were fabricated through anodic oxidation of NiTi alloy and further
      annealing treatment. The hydrogen sensing properties of the nanotube sensor were
      investigated. It was found that the Ni-doped TiO2 nanotubes were sensitive to an
      atmosphere of 1,000 ppm hydrogen, showing a good response at both room
      temperature and elevated temperatures. A First-Principle simulation revealed
      that, in comparison with pure anatase TiO2 oxide, Ni doping in the TiO2 oxide
      could result in a decreased bandgap. When the oxide sensor adsorbed a certain
      amount of hydrogen the bandgap increased and the acceptor impurity levels was
      generated, which resulted in a change of the sensor resistance. 

PMID- 23881125
TI  - Seismic target classification using a wavelet packet manifold in unattended
      ground sensors systems.
AB  - One of the most challenging problems in target classification is the extraction
      of a robust feature, which can effectively represent a specific type of targets.
      The use of seismic signals in unattended ground sensor (UGS) systems makes this
      problem more complicated, because the seismic target signal is non-stationary,
      geology-dependent and with high-dimensional feature space. This paper proposes a
      new feature extraction algorithm, called wavelet packet manifold (WPM), by
      addressing the neighborhood preserving embedding (NPE) algorithm of manifold
      learning on the wavelet packet node energy (WPNE) of seismic signals. By
      combining non-stationary information and low-dimensional manifold information,
      WPM provides a more robust representation for seismic target classification. By
      using a K nearest neighbors classifier on the WPM signature, the algorithm of
      wavelet packet manifold classification (WPMC) is proposed. Experimental results
      show that the proposed WPMC can not only reduce feature dimensionality, but also
      improve the classification accuracy up to 95.03%. Moreover, compared with state
      of-the-art methods, WPMC is more suitable for UGS in terms of recognition ratio
      and computational complexity. 

PMID- 23881126
TI  - Rapid quantitative detection of Brucella melitensis by a label-free impedance
      immunosensor based on a gold nanoparticle-modified screen-printed carbon
      electrode.
AB  - A rapid and simple method for quantitative monitoring of Brucella melitensis
      using electrochemical impedance spectroscopy (EIS) is reported for the first
      time. The label-free immunosensors were fabricated by immobilizing Brucella
      melitensis antibody on the surface of gold nanoparticle-modified screen-printed
      carbon electrodes (GNP-SPCEs). Cyclic voltammetry (CV) and EIS were used to
      characterize the Brucella melitensis antigen interaction on the surface of GNP
      SPCEs with antibody. A general electronic equivalent model of an electrochemical
      cell was introduced for interpretation of the impedance components of the system.
      The results showed that the change in electron-transfer resistance (Rct) was
      significantly different due to the binding of Brucella melitensis cells. A linear
      relationship between the Rct variation and logarithmic value of the cell
      concentration was found from 4 * 10(4) to 4 * 10(6) CFU/mL in pure culture. The
      label-free impedance biosensor was able to detect as low as 1 * 10(4) and 4 *
      10(5) CFU/mL of Brucella melitensis in pure culture and milk samples,
      respectively, in less than 1.5 h. Moreover, a good selectivity versus Escherichia
      coli O157:H7 and Staphylococcus aureus cells was obtained for our developed
      immunosensor demonstrating its specificity towards only Brucella melitensis.

PMID- 23881127
TI  - Radioactive quality evaluation and cross validation of data from the HJ-1A/B
      satellites' CCD sensors.
AB  - Data from multiple sensors are frequently used in Earth science to gain a more
      complete understanding of spatial information changes. Higher quality and mutual
      consistency are prerequisites when multiple sensors are jointly used. The HJ-1A/B
      satellites successfully launched on 6 September 2008. There are four charge
      coupled device (CCD) sensors with uniform spatial resolutions and spectral range
      onboard the HJ-A/B satellites. Whether these data are keeping consistency is a
      major issue before they are used. This research aims to evaluate the data
      consistency and radioactive quality from the four CCDs. First, images of urban,
      desert, lake and ocean are chosen as the objects of evaluation. Second, objective
      evaluation variables, such as mean, variance and angular second moment, are used
      to identify image performance. Finally, a cross validation method are used to
      ensure the correlation of the data from the four HJ-1A/B CCDs and that which is
      gathered from the moderate resolution imaging spectro-radiometer (MODIS). The
      results show that the image quality of HJ-1A/B CCDs is stable, and the digital
      number distribution of CCD data is relatively low. In cross validation with
      MODIS, the root mean square errors of bands 1, 2 and 3 range from 0.055 to 0.065,
      and for band 4 it is 0.101. The data from HJ-1A/B CCD have better consistency. 

PMID- 23881128
TI  - Gauge factor and stretchability of silicon-on-polymer strain gauges.
AB  - Strain gauges are widely applied to measure mechanical deformation of structures
      and specimens. While metallic foil gauges usually have a gauge factor slightly
      over 2, single crystalline silicon demonstrates intrinsic gauge factors as high
      as 200. Although silicon is an intrinsically stiff and brittle material, flexible
      and even stretchable strain gauges have been achieved by integrating thin silicon
      strips on soft and deformable polymer substrates. To achieve a fundamental
      understanding of the large variance in gauge factor and stretchability of
      reported flexible/stretchable silicon-on-polymer strain gauges, finite element
      and analytically models are established to reveal the effects of the length of
      the silicon strip, and the thickness and modulus of the polymer substrate.
      Analytical results for two limiting cases, i.e., infinitely thick substrate and
      infinitely long strip, have found good agreement with FEM results. We have
      discovered that strains in silicon resistor can vary by orders of magnitude with
      different substrate materials whereas strip length or substrate thickness only
      affects the strain level mildly. While the average strain in silicon reflects the
      gauge factor, the maximum strain in silicon governs the stretchability of the
      system. The tradeoff between gauge factor and stretchability of silicon-on
      polymer strain gauges has been proposed and discussed. 

PMID- 23881130
TI  - A bandwidth-efficient service for local information dissemination in sparse to
      dense roadways.
AB  - Thanks to the research on Vehicular Ad Hoc Networks (VANETs), we will be able to
      deploy applications on roadways that will contribute to energy efficiency through
      a better planning of long trips. With this goal in mind, we have designed a
      gas/charging station advertising system, which takes advantage of the broadcast
      nature of the network. We have found that reducing the number of total sent
      packets is important, as it allows for a better use of the available bandwidth.
      We have designed improvements for a distance-based flooding scheme, so that it
      can support the advertising application with good results in sparse to dense
      roadway scenarios. 

PMID- 23881129
TI  - Direct electrochemistry of hemoglobin immobilized on a functionalized multi
      walled carbon nanotubes and gold nanoparticles nanocomplex-modified glassy carbon
      electrode.
AB  - Direct electron transfer of hemoglobin (Hb) was realized by immobilizing Hb on a
      carboxyl functionalized multi-walled carbon nanotubes (FMWCNTs) and gold
      nanoparticles (AuNPs) nanocomplex-modified glassy carbon electrode. The
      ultraviolet-visible absorption spectrometry (UV-Vis), transmission electron
      microscopy (TEM) and Fourier transform infrared (FTIR) methods were utilized for
      additional characterization of the AuNPs and FMWCNTs. The cyclic voltammogram of
      the modified electrode has a pair of well-defined quasi-reversible redox peaks
      with a formal potential of -0.270 +/- 0.002 V (vs. Ag/AgCl) at a scan rate of
      0.05 V/s. The heterogeneous electron transfer constant (ks) was evaluated to be
      4.0 +/- 0.2 s(-1). The average surface concentration of electro-active Hb on the
      surface of the modified glassy carbon electrode was calculated to be 6.8 +/- 0.3
      * 10(-10) mol cm(-2). The cathodic peak current of the modified electrode
      increased linearly with increasing concentration of hydrogen peroxide (from 0.05
      nM to 1 nM) with a detection limit of 0.05 +/- 0.01 nM. The apparent Michaelis
      Menten constant (K(m)(app)) was calculated to be 0.85 +/- 0.1 nM. Thus, the
      modified electrode could be applied as a third generation biosensor with high
      sensitivity, long-term stability and low detection limit.

PMID- 23881131
TI  - Fibre optic sensors for selected wastewater characteristics.
AB  - Demand for online and real-time measurements techniques to meet environmental
      regulation and treatment compliance are increasing. However the conventional
      techniques, which involve scheduled sampling and chemical analysis can be
      expensive and time consuming. Therefore cheaper and faster alternatives to
      monitor wastewater characteristics are required as alternatives to conventional
      methods. This paper reviews existing conventional techniques and optical and
      fibre optic sensors to determine selected wastewater characteristics which are
      colour, Chemical Oxygen Demand (COD) and Biological Oxygen Demand (BOD). The
      review confirms that with appropriate configuration, calibration and fibre
      features the parameters can be determined with accuracy comparable to
      conventional method. With more research in this area, the potential for using FOS
      for online and real-time measurement of more wastewater parameters for various
      types of industrial effluent are promising. 

PMID- 23881132
TI  - Dependence of the impact response of polyvinylidene fluoride sensors on their
      supporting materials' elasticity.
AB  - Polyvinylidene fluoride (PVDF) is popular sensing material because of its unique
      piezoelectric characteristics. In this work an impact sensor was prepared from a
      sandwiched structure PVDF film, and the related detection circuits were
      presented. The dependence of the PVDF sensors' response on the elasticity of the
      supporting materials was examined and discussed. Here two response indexes were
      discussed, which were the peak-to-peak voltage (Vpp) and the recovery time.
      Firstly, falling impact experiments were executed on desk-supported PVDF sensors
      (100 mm PVDF film) using free falls of different weights from different heights.
      Then the same shock experiments were repeated on the same sensor, but changing
      the backstops to a sponge and rubber, respectively. On the desk, the values of
      Vpp were bigger than when the other two backstops were used; but the changes of
      the impact energy could not be reflected by the PVDF sensor when it was supported
      by a hard material. It was found that the biggest sensitivity of the voltage
      response (about 96.62 V/J) was obtained by the sponge-supported sensor; for the
      same sensor, when it was supported by rubber, the slope was 82.26 V/J. Moreover,
      the recovery time for the desk-supported sensor was almost constant, varying from
      0.15 to 0.18 s, while for the same sensor supported by sponge or rubber, its
      recovery time changed with the shifting of the impact energy in the range of
      0.02~0.36 s, but no pattern could be found in the recovery-time characteristics. 

PMID- 23881133
TI  - LMD method and multi-class RWSVM of fault diagnosis for rotating machinery using
      condition monitoring information.
AB  - Timely and accurate condition monitoring and fault diagnosis of rotating
      machinery are very important to maintain a high degree of availability,
      reliability and operational safety. This paper presents a novel intelligent
      method based on local mean decomposition (LMD) and multi-class reproducing
      wavelet support vector machines (RWSVM), which is applied to diagnose rotating
      machinery faults. First, the sensor-based vibration signals measured from the
      rotating machinery are preprocessed by the LMD method and product functions (PFs)
      are produced. Second, statistic features are extracted to acquire more fault
      characteristic information from the sensitive PF. Finally, these features are fed
      into a multi-class RWSVM to identify the rotating machinery health conditions.
      The experimental results validate the effectiveness of the proposed RWSVM method
      in identifying rotating machinery fault patterns accurately and effectively and
      its superiority over that based on the general SVM. 

PMID- 23881134
TI  - RoCoMAR: robots' controllable mobility aided routing and relay architecture for
      mobile sensor networks.
AB  - In a practical deployment, mobile sensor network (MSN) suffers from a low
      performance due to high node mobility, time-varying wireless channel properties,
      and obstacles between communicating nodes. In order to tackle the problem of low
      network performance and provide a desired end-to-end data transfer quality, in
      this paper we propose a novel ad hoc routing and relaying architecture, namely
      RoCoMAR (Robots' Controllable Mobility Aided Routing) that uses robotic nodes'
      controllable mobility. RoCoMAR repeatedly performs link reinforcement process
      with the objective of maximizing the network throughput, in which the link with
      the lowest quality on the path is identified and replaced with high quality links
      by placing a robotic node as a relay at an optimal position. The robotic node
      resigns as a relay if the objective is achieved or no more gain can be obtained
      with a new relay. Once placed as a relay, the robotic node performs adaptive link
      maintenance by adjusting its position according to the movements of regular
      nodes. The simulation results show that RoCoMAR outperforms existing ad hoc
      routing protocols for MSN in terms of network throughput and end-to-end delay. 

PMID- 23881136
TI  - Multi-view human activity recognition in distributed camera sensor networks.
AB  - With the increasing demand on the usage of smart and networked cameras in
      intelligent and ambient technology environments, development of algorithms for
      such resource-distributed networks are of great interest. Multi-view action
      recognition addresses many challenges dealing with view-invariance and occlusion,
      and due to the huge amount of processing and communicating data in real life
      applications, it is not easy to adapt these methods for use in smart camera
      networks. In this paper, we propose a distributed activity classification
      framework, in which we assume that several camera sensors are observing the
      scene. Each camera processes its own observations, and while communicating with
      other cameras, they come to an agreement about the activity class. Our method is
      based on recovering a low-rank matrix over consensus to perform a distributed
      matrix completion via convex optimization. Then, it is applied to the problem of
      human activity classification. We test our approach on IXMAS and MuHAVi datasets
      to show the performance and the feasibility of the method. 

PMID- 23881137
TI  - In-plane resonant nano-electro-mechanical sensors: a comprehensive study on
      design, fabrication and characterization challenges.
AB  - The newly proposed in-plane resonant nano-electro-mechanical (IP R-NEM) sensor,
      that includes a doubly clamped suspended beam and two side electrodes, achieved a
      mass sensitivity of less than zepto g/Hz based on analytical and numerical
      analyses. The high frequency characterization and numerical/analytical studies of
      the fabricated sensor show that the high vacuum measurement environment will ease
      the resonance detection using the capacitance detection technique if only the
      thermoelsatic damping plays a dominant role for the total quality factor of the
      sensor. The usage of the intrinsic junction-less field-effect-transistor (JL FET)
      for the resonance detection of the sensor provides a more practical detection
      method for this sensor. As the second proposed sensor, the introduction of the
      monolithically integrated in-plane MOSFET with the suspended beam provides
      another solution for the ease of resonance frequency detection with similar
      operation to the junction-less transistor in the IP R-NEM sensor. The challenging
      fabrication technology for the in-plane resonant suspended gate field-effect
      transistor (IP RSG-FET) sensor results in some post processing and simulation
      steps to fully explore and improve the direct current (DC) characteristics of the
      sensor for the consequent high frequency measurement. The results of modeling and
      characterization in this research provide a realistic guideline for these
      potential ultra-sensitive NEM sensors. 

PMID- 23881135
TI  - Fluorosomes: fluorescent virus-like nanoparticles that represent a convenient
      tool to visualize receptor-ligand interactions.
AB  - Viruses are the smallest life forms and parasitize on many eukaryotic organisms,
      including humans. Consequently, the study of viruses and viral diseases has had
      an enormous impact on diverse fields of biology and medicine. Due to their often
      pathogenic properties, viruses have not only had a strong impact on the
      development of immune cells but also on shaping entire immune mechanisms in their
      hosts. In order to better characterize virus-specific surface receptors, pathways
      of virus entry and the mechanisms of virus assembly, diverse methods to visualize
      virus particles themselves have been developed in the past decades. Apart from
      characterization of virus-specific mechanisms, fluorescent virus particles also
      serve as valuable platforms to study receptor-ligand interactions. Along those
      lines the authors have developed non-infectious virus-like nanoparticles (VNP),
      which can be decorated with immune receptors of choice and used for probing
      receptor-ligand interactions, an especially interesting application in the field
      of basic but also applied immunology research. To be able to better trace
      receptor-decorated VNP the authors have developed technology to introduce
      fluorescent proteins into such particles and henceforth termed them fluorosomes
      (FS). Since VNP are assembled in a simple expression system relying on HEK-293
      cells, gene-products of interest can be assembled in a simple and straightforward
      fashion-one of the reasons why the authors like to call fluorosomes 'the poor
      man's staining tool'. Within this review article an overview on virus particle
      assembly, chemical and recombinant methods of virus particle labeling and
      examples on how FS can be applied as sensors to monitor receptor-ligand
      interactions on leukocytes are given. 

PMID- 23881138
TI  - Effect of tensile strain on thermal conductivity in monolayer graphene
      nanoribbons: a molecular dynamics study.
AB  - The thermal conductivity of monolayer graphene nanoribbons (GNRs) with different
      tensile strain is investigated by using a nonequilibrium molecular dynamics
      method. Significant increasing amplitude of the molecular thermal vibration,
      molecular potential energy vibration and thermal conductivity vibration of
      stretching GNRs were detected. Some 20%~30% thermal conductivity decay is found
      in 9%~15% tensile strain of GNR cases. It is explained by the fact that GNR
      structural ridges scatter some low-frequency phonons which pass in the direction
      perpendicular to the direction of GNR stretching which was indicated by a phonon
      density of state investigation. 

PMID- 23881139
TI  - A mobile robots experimental environment with event-based wireless communication.
AB  - An experimental platform to communicate between a set of mobile robots through a
      wireless network has been developed. The mobile robots get their position through
      a camera which performs as sensor. The video images are processed in a PC and a
      Waspmote card sends the corresponding position to each robot using the ZigBee
      standard. A distributed control algorithm based on event-triggered communications
      has been designed and implemented to bring the robots into the desired formation.
      Each robot communicates to its neighbors only at event times. Furthermore, a
      simulation tool has been developed to design and perform experiments with the
      system. An example of usage is presented. 

PMID- 23881140
TI  - Electric field and current transport mechanisms in Schottky CdTe X-ray detectors
      under perturbing optical radiation.
AB  - Schottky CdTe X-ray detectors exhibit excellent spectroscopic performance but
      suffer from instabilities. Hence it is of extreme relevance to investigate their
      electrical properties. A systematic study of the electric field distribution and
      the current flowing in such detectors under optical perturbations is presented
      here. The detector response is explored by varying experimental parameters, such
      as voltage, temperature, and radiation wavelength. The strongest perturbation is
      observed under 850 nm irradiation, bulk carrier recombination becoming effective
      there. Cathode and anode irradiations evidence the crucial role of the contacts,
      the cathode being Ohmic and the anode blocking. In particular, under irradiation
      of the cathode, charge injection occurs and peculiar kinks, typical of trap
      filling, are observed both in the current-voltage characteristic and during
      transients. The simultaneous access to the electric field and the current
      highlights the correlation between free and fixed charges, and unveils carrier
      transport/collection mechanisms otherwise hidden. 

PMID- 23881141
TI  - BeiDou inter-satellite-type bias evaluation and calibration for mixed receiver
      attitude determination.
AB  - The Chinese BeiDou system (BDS), having different types of satellites, is an
      important addition to the ever growing system of Global Navigation Satellite
      Systems (GNSS). It consists of Geostationary Earth Orbit (GEO) satellites,
      Inclined Geosynchronous Satellite Orbit (IGSO) satellites and Medium Earth Orbit
      (MEO) satellites. This paper investigates the receiver-dependent bias between
      these satellite types, for which we coined the name "inter-satellite-type bias"
      (ISTB), and its impact on mixed receiver attitude determination. Assuming
      different receiver types may have different delays/biases for different satellite
      types, we model the differential ISTBs among three BeiDou satellite types and
      investigate their existence and their impact on mixed receiver attitude
      determination. Our analyses using the real data sets from Curtin's GNSS array
      consisting of different types of BeiDou enabled receivers and series of zero
      baseline experiments with BeiDou-enabled receivers reveal the existence of non
      zero ISTBs between different BeiDou satellite types. We then analyse the impact
      of these biases on BeiDou-only attitude determination using the constrained (C
      )LAMBDA method, which exploits the knowledge of baseline length. Results
      demonstrate that these biases could seriously affect the integer ambiguity
      resolution for attitude determination using mixed receiver types and that a
      priori correction of these biases will dramatically improve the success rate. 

PMID- 23881142
TI  - Photo-detectors integrated with resonant tunneling diodes.
AB  - We report on photo-detectors consisting of an optical waveguide that incorporates
      a resonant tunneling diode (RTD). Operating at wavelengths around 1.55 MUm in the
      optical communications C band we achieve maximum sensitivities of around 0.29 A/W
      which is dependent on the bias voltage. This is due to the nature of RTD
      nonlinear current-voltage characteristic that has a negative differential
      resistance (NDR) region. The resonant tunneling diode photo-detector (RTD-PD) can
      be operated in either non-oscillating or oscillating regimes depending on the
      bias voltage quiescent point. The oscillating regime is apparent when the RTD-PD
      is biased in the NDR region giving rise to electrical gain and microwave self
      sustained oscillations Taking advantage of the RTD's NDR distinctive
      characteristics, we demonstrate efficient detection of gigahertz (GHz) modulated
      optical carriers and optical control of a RTD GHz oscillator. RTD-PD based
      devices can have applications in generation and optical control of GHz low-phase
      noise oscillators, clock recovery systems, and fiber optic enabled radio
      frequency communication systems. 

PMID- 23881143
TI  - Fixed-base comb with window-non-adjacent form (NAF) method for scalar
      multiplication.
AB  - Elliptic curve cryptography (ECC) is one of the most promising public-key
      techniques in terms of short key size and various crypto protocols. For this
      reason, many studies on the implementation of ECC on resource-constrained devices
      within a practical execution time have been conducted. To this end, we must focus
      on scalar multiplication, which is the most expensive operation in ECC. A number
      of studies have proposed pre-computation and advanced scalar multiplication using
      a non-adjacent form (NAF) representation, and more sophisticated approaches have
      employed a width-w NAF representation and a modified pre-computation table. In
      this paper, we propose a new pre-computation method in which zero occurrences are
      much more frequent than in previous methods. This method can be applied to
      ordinary group scalar multiplication, but it requires large pre-computation
      table, so we combined the previous method with ours for practical purposes. This
      novel structure establishes a new feature that adjusts speed performance and
      table size finely, so we can customize the pre-computation table for our own
      purposes. Finally, we can establish a customized look-up table for embedded
      microprocessors. 

PMID- 23881144
TI  - An in-situ real-time optical fiber sensor based on surface plasmon resonance for
      monitoring the growth of TiO2 thin films.
AB  - An optical fiber sensor based on surface plasmon resonance (SPR) is proposed for
      monitoring the thickness of deposited nano-thin films. A side-polished multimode
      SPR optical fiber sensor with an 850 nm-LD is used as the transducing element for
      real-time monitoring of the deposited TiO2 thin films. The SPR optical fiber
      sensor was installed in the TiO2 sputtering system in order to measure the
      thickness of the deposited sample during TiO2 deposition. The SPR response
      declined in real-time in relation to the growth of the thickness of the TiO2 thin
      film. Our results show the same trend of the SPR response in real-time and in
      spectra taken before and after deposition. The SPR transmitted intensity changes
      by approximately 18.76% corresponding to 50 nm of deposited TiO2 thin film. We
      have shown that optical fiber sensors utilizing SPR have the potential for real
      time monitoring of the SPR technology of nanometer film thickness. The compact
      size of the SPR fiber sensor enables it to be positioned inside the deposition
      chamber, and it could thus measure the film thickness directly in real-time. This
      technology also has potential application for monitoring the deposition of other
      materials. Moreover, in-situ real-time SPR optical fiber sensor technology is in
      inexpensive, disposable technique that has anti-interference properties, and the
      potential to enable on-line monitoring and monitoring of organic coatings. 

PMID- 23881145
TI  - Further in-vitro characterization of an implantable biosensor for ethanol
      monitoring in the brain.
AB  - Ethyl alcohol may be considered one of the most widespread central nervous system
      (CNS) depressants in Western countries. Because of its toxicological and
      neurobiological implications, the detection of ethanol in brain extracellular
      fluid (ECF) is of great importance. In a previous study, we described the
      development and characterization of an implantable biosensor successfully used
      for the real-time detection of ethanol in the brain of freely-moving rats. The
      implanted biosensor, integrated in a low-cost telemetry system, was demonstrated
      to be a reliable device for the short-time monitoring of exogenous ethanol in
      brain ECF. In this paper we describe a further in-vitro characterization of the
      above-mentioned biosensor in terms of oxygen, pH and temperature dependence in
      order to complete its validation. With the aim of enhancing ethanol biosensor
      performance, different enzyme loadings were investigated in terms of apparent
      ethanol Michaelis-Menten kinetic parameters, viz. IMAX, KM and linear region
      slope, as well as ascorbic acid interference shielding. The responses of
      biosensors were studied over a period of 28 days. The overall findings of the
      present study confirm the original biosensor configuration to be the best of
      those investigated for in-vivo applications up to one week after implantation. 

PMID- 23881146
TI  - Temperature-insensitive bend sensor using entirely centered Erbium doping in the
      fiber core.
AB  - A fiber based bend sensor using a uniquely designed Bend-Sensitive Erbium Doped
      Fiber (BSEDF) is proposed and demonstrated. The BSEDF has two core regions,
      namely an undoped outer region with a diameter of about 9.38 MUm encompassing a
      doped, inner core region with a diameter of 4.00 MUm. The doped core region has
      about 400 ppm of an Er2O3 dopant. Pumping the BSEDF with a conventional 980 nm
      laser diode gives an Amplified Spontaneous Emission (ASE) spectrum spanning from
      1,510 nm to over 1,560 nm at the output power level of about -58 dBm. The ASE
      spectrum has a peak power of -52 dBm at a central wavelength of 1,533 nm when not
      spooled. Spooling the BSEDF with diameters of 10 cm to 2 cm yields decreasing
      peak powers from -57.0 dBm to -61.8 dBm, while the central wavelength remains
      unchanged. The output is highly stable over time, with a low temperature
      sensitivity of around ~0.005 dBm/ degrees C, thus allowing for the development of
      a highly stable sensor system based in the change of the peak power alone. 

PMID- 23881149
TI  - Alarming rise in prevalence of atherogenic dyslipidaemia in the black population
      of Cape Town: the Cardiovascular Risk in Black South Africans (CRIBSA) study.
AB  - OBJECTIVES: To determine the prevalence, determinants, and management of
      dyslipidaemia in the 25-74-year-old urban black population of Cape Town and
      examine the changes between 1990 and 2008/09 in the 25-64-year-old sample.
      METHODS: In 2008/09, a representative cross-sectional sample, stratified for age
      and sex, was randomly selected from the same townships sampled in 1990.
      Cardiovascular disease (CVD) risk factors were determined by questionnaires,
      clinical measurements, and fasting biochemical analyses. Survey logistic
      regression analysis assessed the determinants of raised low-density lipoprotein
      cholesterol (LDL-C). RESULTS: There were 1099 participants in 2008/09 (392 men
      and 707 women; response rate 86%). The prevalence of raised total cholesterol
      (TC), raised LDL-C, and reduced high-density lipoprotein cholesterol (HDL-C) were
      25.2% (95% confidence interval, CI, 20.0-31.3), 37.8% (95% CI 32.5-43.4), and
      55.2% (95% CI 49.9-60.4) in men and 23.1% (95% CI 20.0-26.5), 47.0% (95% CI 43.1
      50.9), and 66.8% (95% CI 62.9-70.5) in women, respectively. Between 1990 and
      2008/09, raised LDL-C and reduced HDL-C prevalence increased significantly with
      no change for raised TC. Among participants with raised LDL-C, only 2.6% were
      aware of their diagnosis, 2.7% were on treatment, and 1.5% had LDL-C <3 mmol/l.
      In the logistic model, increasing age (odds ratio, OR, 1.04, 95% CI 1.03-1.05; p
      < 0.001), rising body mass index (OR 1.03, 95% CI 1.01-1.05; p = 0.003), and fat
      intake >=30% of diet (OR 1.37, 95% CI 1.02-1.85; p = 0.035) were significantly
      associated with LDL-C >=3 mmol/l but not sex, physical activity, or urbanization.
      CONCLUSIONS: The dyslipidaemia pattern in this population requires full lipogram
      screening in high-risk individuals and demands improved management using a total
      CVD risk approach.

PMID- 23881151
TI  - In search of useful methods for measuring health and economic consequences of
      antimicrobial resistance.

PMID- 23881150
TI  - Use of multilocus variable number of tandem repeats analysis genotyping to
      determine the role of asymptomatic carriers in Clostridium difficile
      transmission.
AB  - BACKGROUND: Previous studies have suggested that asymptomatic carriers of
      toxigenic Clostridium difficile are a source of hospital-associated (HA)
      infections. Multilocus variable number of tandem repeats analysis (MLVA) is a
      highly discriminatory molecular subtyping tool that helps to determine possible
      transmission sources. METHODS: Clostridium difficile isolates were recovered from
      perirectal swabs collected for vancomycin-resistant Enterococcus (VRE)
      surveillance as well as from clinical C. difficile toxin-positive stool samples
      from July to November 2009 at the University of Pittsburgh Medical Center
      Presbyterian (UPMC). MLVA was performed to determine the genetic relationships
      between isolates from asymptomatic carriers and patients with HA C. difficile
      infection (HA-CDI). Asymptomatic carriage and HA-CDI isolates were considered to
      be associated if the carriage isolate was collected before the HA-CDI isolate and
      if the MLVA genotypes had a summed tandem-repeat difference of <= 2. RESULTS: Of
      3006 patients screened, 314 (10.4%) were positive for toxigenic C. difficile, of
      whom 226 (7.5%) were detected only by VRE surveillance cultures. Of 56 incident
      cases of CDI classified as HA at UPMC during the study with available isolates,
      17 (30%) cases were associated with CDI patients, whereas 16 (29%) cases were
      associated with carriers. Transmission events from prior bed occupants with CDI
      (n = 2) or carriers (n = 2) were identified in 4 of 56 cases. CONCLUSIONS: In our
      hospital with an established infection control program designed to contain
      transmission from symptomatic CDI patients, asymptomatic carriers appear to have
      played an important role in transmission. Identification and isolation of
      carriers may be necessary to further reduce transmission of C. difficile in such
      settings.

PMID- 23881152
TI  - Editorial Commentary: looking to the future: vertical vs horizontal prevention of
      Clostridium difficile infections.

PMID- 23881153
TI  - Origin and molecular characteristics of a novel 2013 avian influenza A(H6N1)
      virus causing human infection in Taiwan.

PMID- 23881154
TI  - An evaluation of CT-scan to locate the femoral head centre and its implication
      for hip surgeons.
AB  - PURPOSE: The aim of this preliminary study was to determine the accuracy of CT
      scan to locate the femoral head centre. METHODS: Eleven dried femurs were
      included for study. Three techniques were compared to determine femoral head
      centre (FHC) location: CT-scan, Motion Analysis and Faro-Arm. Markers were stuck
      on each femur to create a system of coordinates. Femurs lied on their posterior
      parts (bicondylar plane). Several points around the femoral head were palpated
      (Motion Analysis and Faro-Arm) or determined (Amira software for CT-scans). By a
      least-square regression method, the FHC location in 3D was defined for each
      technique. RESULTS: The results of the FHC location determined by the CT-scan
      technique were compared with those measured by the faro-arm and the Motion
      Analysis techniques. The coordinates (X, Y, Z) of the FHC were compared between
      the three methods, and no statistical difference was found (p = 0.99). In a 3D
      plot, this gave a mean difference of 1.3 mm. The mean radius of the femoral head
      was of 22.5 mm (p = 0.6). CONCLUSIONS: CT-scan is as accurate and reliable as
      gold-standard techniques (motion and faro-arm). Locating FHC before and after hip
      arthroplasty would allow hip surgeons to determine and compare 3D orientation of
      the upper-end of femur: offset, height and anteversion.

PMID- 23881155
TI  - Ag@SiO2 core-shell nanoparticles on silicon nanowire arrays as ultrasensitive and
      ultrastable substrates for surface-enhanced Raman scattering.
AB  - Ag nanoparticles (NPs) coated with silica nanolayers were decorated onto a large
      scale and uniform silicon nanowire array (SiNWA) by simple chemical etching and
      metal reduction processes. The three-dimensional Ag/SiNWAs thus formed are
      employed as a substrate for surface-enhanced Raman scattering (SERS), and a
      detection limit for rhodamine 6G as low as 10(-16) M and a Raman enhancement
      factor as large as 10(14) were obtained. Simulation results show that two kinds
      of inter-Ag-NP nanogaps in three-dimensional geometry create a huge number of
      SERS 'hot spots' where electromagnetic fields are substantially amplified,
      contributing to the higher SERS sensitivity and lower detection limit. The
      excellent SERS stability of Ag/SiNWAs is attributed to the presence of the SiO2
      nanolayer around Ag NPs that prevented the Ag NP surface from being oxidized. The
      calibration of the Raman peak intensities of rhodamine 6G and thiram allowed
      their quantitative detection. Our finding is a significant advance in developing
      SERS substrates for the fast and quantitative detection of trace organic
      molecules. 

PMID- 23881156
TI  - In-depth proteomic analysis of human tropomyosin by top-down mass spectrometry.
AB  - Tropomyosins (Tms) are a family of highly conserved actin-binding proteins that
      play critical roles in a variety of processes, most notably, in the regulation of
      muscle contraction and relaxation. It is well known that different Tm isoforms
      have distinct functions and that altered expression of Tm isoforms could lead to
      changes in cardiac structure and function. To precisely define Tm isoform
      expression in the human heart, towards a better understanding of their functional
      roles, we have employed top-down mass spectrometry for in-depth proteomic
      characterization of Tm isoforms. Using a minimal amount of human heart tissue
      from rejected donor organs, we confirmed the presence of multiple Tm isoforms
      including alpha-Tm, beta-Tm and kappa-Tm in the human heart, with alpha-Tm being
      the predominant isoform, followed by minor isoforms of beta-Tm and kappa-Tm.
      Interestingly, our data revealed regional variations of Tm isoforms and post
      translational modifications in the human heart. Specifically, the expression
      level of kappa-Tm was highest in the left atrium but nearly undetectable in the
      left ventricle. The phosphorylation level of alpha-Tm (palpha-Tm) was
      significantly higher in the atria than it was in the ventricles. The sequences of
      all Tm isoforms were characterized and the sites of post-translational
      modifications were localized. Clearly, top-down mass spectrometry is an
      attractive method for comprehensive characterization of Tm isoforms and post
      translational modifications since it can universally detect and quantify all
      types of protein modifications without a priori knowledge and without the need
      for specific antibodies. 

PMID- 23881157
TI  - Neurological soft signs and brainstem morphology in first-episode schizophrenia.
AB  - BACKGROUND: Minor motor and sensory deficits or neurological soft signs (NSS)
      have frequently been reported in patients with schizophrenia at any stage of
      their illness. NSS have been demonstrated to correlate with neuroanatomical
      abnormalities in various brain regions. Despite its important role in the
      integration and coordination of automatic motor actions, the brainstem has so far
      rather been ignored in previous neuroimaging studies on NSS in schizophrenia.
      METHOD: We investigated 21 right-handed first-episode schizophrenia patients
      using high-resolution magnetic resonance imaging at 3 T. The severity of NSS was
      measured with the Heidelberg Scale. Associations between NSS and both brainstem
      volume and shape changes were examined. RESULTS: Higher NSS scores were
      significantly associated with structural alterations in the brainstem. According
      to volume measurements higher NSS scores correlated with global changes of the
      brainstem. Using shape analyses these associations referred to regionally
      specific morphometric alterations predominantly in the midbrain and pons.
      CONCLUSION: The findings suggest that brainstem morphometric alterations are
      associated with the severity of NSS in patients with first-episode schizophrenia.
      They further indicate the involvement of the brainstem in the pathogenesis of
      schizophrenia.

PMID- 23881158
TI  - Pain management following new and long-standing spinal cord injury: a pilot study
      of changes in pain intensity experienced during the day.
AB  - The aim of the study was to examine variations in pain intensity during the day
      experienced by patients with spinal cord injury. Fourteen consecutive patients
      had clinical and demographic data recorded. Pain intensity was recorded using a
      Graphic Rating Scale (GRS) at 2-3-h intervals. Patients were grouped according to
      maximum GRS into mild and severe groups at assessment (T0). Changes of one-third
      in GRS were deemed clinically significant. Eight men and six women (mean age
      53.1; SD 16.5; range 28-75) were studied. Seven patients with mild pain tended to
      deteriorate and those with severe pain to improve. Eight patients demonstrated
      clinically significant changes. These findings suggest inadequate pain control
      early morning for one group and increasing pain during the day for another. Use
      of such simple scores over time would enhance pain rehabilitation for all spinal
      cord injury patients. Usual GRS reporting may mask clinically significant,
      treatable, changes in pain. 

PMID- 23881159
TI  - How patients with stroke adjust their step length to step over obstacles.
AB  - Step adjustment under temporal constraint is compromised following stroke.
      However, how step adjustment occurs under no temporal constraint remains unclear.
      The aim of this study was to investigate how patients with stroke adjust their
      step length to step over obstacles under no temporal constraint. Twelve patients
      with stroke and 12 age-matched and sex-matched individuals without stroke
      participated in an experiment involving the task of stepping over obstacles. Each
      participant's steps were measured by a footprint method and classified as a long
      step, short-step, or even-step strategy. The differences in step length
      adjustment between patients with and without stroke were analyzed. Stroke
      survivors adjusted their step length in different ways depending on whether they
      led with the affected or the unaffected limb. If patients with stroke stepped
      over the obstacle by leading with the affected limb, they chose the short-step
      strategy. This strategy is probably intended to enhance accuracy and maintain
      stability. In conclusion, patients with stroke utilize a different step
      adjustment strategy to individuals without stroke, even in the absence of
      temporal constraint. 

PMID- 23881160
TI  - The ups and downs of somatic cell nucleus transfer (SCNT) in humans.
AB  - Achieving successful somatic cell nuclear transfer (SCNT) in the human and
      subhuman primate relative to other mammals has been questioned for a variety of
      technical and logistical issues. Here we summarize the gradual evolution of SCNT
      technology from the perspective of oocyte quality and cell cycle status that has
      recently led to the demonstration of feasibility in the human for deriving
      chromosomally normal stem cells lines. With these advances in hand, prospects for
      therapeutic cloning must be entertained in a conscientious, rigorous, and timely
      fashion before broad spectrum clinical applications are undertaken. 

PMID- 23881162
TI  - In focus in Bad Ischl: Golgi apparatus 2013.

PMID- 23881161
TI  - Role of gap junction-mediated communications in regulating large-scale chromatin
      configuration remodeling and embryonic developmental competence acquisition in
      fully grown bovine oocyte.
AB  - PURPOSE: This study was aimed to test the hypothesis that gap junction mediated
      communications (GJC) are required to allow the progressive chromatin
      configuration remodeling (from GV1 to GV3) process to occur in fully grown
      oocytes in order to gain the final step of developmental competence acquisition,
      and that a premature disruption of GJC can alter this process. METHODS: Bovine
      cumulus-oocytes complexes collected from medium antral follicles were cultured
      for 2, 4, 6 and 8 h in the presence of 10(-4) IU/ml of r-hFSH and with 2 mM of
      the non-selective PDE inhibitor 3-isobutyl-1-methyl-xanthine (IBMX) to prevent
      meiotic resumption. GJC functionality and chromatin configuration were monitored
      during the culture period. After meiotic arrest, the developmental capability of
      oocytes was assessed after IVM and IVF. RESULTS: IBMX was effective in
      significantly sustaining GJC up to 6 h and maintaining meiotic arrest, when
      compared to control group. Moreover, the percentage of oocytes with less
      condensed chromatin (GV1) decreased within 4 h of culture, while the proportion
      of GV2 oocytes gradually increased up to 6 h. Interestingly, a decline in the
      proportion of GV2 oocytes and an increase in the proportion of GV3 oocytes were
      observed after 6 h of culture, when the major drop of GJC occurred. On the
      contrary, when GJC were uncoupled by adding 3 mM of 1-heptanol or through cumulus
      cells removal, chromatin condensation occurred rapidly throughout the culture
      period, more promptly in denuded oocytes. Moreover, the maintenance of GJC during
      meiotic arrest was accompanied by a significant increase of developmental
      competence compared to the control, as indicated by a higher percentage of
      hatched blastocysts and blastocyst cell number. CONCLUSIONS: Altogether, our data
      indicate that both paracrine and junctional mechanisms are involved in modulating
      large-scale chromatin structure during the final phase of oocyte differentiation.

PMID- 23881163
TI  - Qualitative and quantitative mass spectrometry imaging of drugs and metabolites
      in tissue at therapeutic levels.
AB  - Mass spectrometry imaging (MSI) is a rapidly evolving technology that yields
      qualitative and quantitative distribution maps of small pharmaceutical-active
      molecules and their metabolites in tissue sections in situ. The simplicity, high
      sensitivity and ability to provide comprehensive spatial distribution maps of
      different classes of biomolecules make MSI a valuable tool to complement
      histopathology for diagnostics and biomarker discovery. In this review,
      qualitative and quantitative MSI of drugs and metabolites in tissue at
      therapeutic levels are discussed and the impact of this technique in drug
      discovery and clinical research is highlighted. 

PMID- 23881165
TI  - Complementary expression and repulsive signaling suggest that EphB2 and ephrin-B1
      are possibly involved in epithelial boundary formation at the squamocolumnar
      junction in the rodent stomach.
AB  - Eph receptors and ephrin ligands are cell-cell communication molecules with well
      defined roles in cell adhesion, migration, and tissue boundary formation.
      However, their expression levels in the squamocolumnar epithelial junction region
      at the distal esophagus are completely unknown. We examined EphB2 and ephrin-B1
      localization in the squamocolumnar epithelial junction region between the
      proximal and distal stomach of the rodents. Immunostaining showed complimentary
      expression patterns along the proximal-to-distal axis of the gastric epithelia
      across the junction: EphB2 expression was maximal around the epithelial junction
      and sharply decreased in the stratified squamous epithelium at a short distance
      from the junction, whereas ephrin-B1 was strongly expressed in the stratified
      squamous epithelium at a distance from the junction and sharply decreased toward
      the junction. These expression patterns suggest that EphB2/ephrin-B1 signaling
      occurs preferentially in the epithelia across the junction, where the receptor
      and ligand expression highly overlap. We also show that (1) EphB2 preferentially
      binds ephrin-B1, and (2) cell repulsion/lateral migration was induced in primary
      cultured gastric keratinocytes on ephrin-B1-Fc- and EphB2-Fc-coated surfaces. On
      the basis of these findings, we propose that EphB2 and ephrin-B1 are possibly
      involved in epithelial boundary formation at the squamocolumnar junction. 

PMID- 23881164
TI  - A three-stage model of Golgi structure and function.
AB  - The Golgi apparatus contains multiple classes of cisternae that differ in
      structure, composition, and function, but there is no consensus about the number
      and definition of these classes. A useful way to classify Golgi cisternae is
      according to the trafficking pathways by which the cisternae import and export
      components. By this criterion, we propose that Golgi cisternae can be divided
      into three classes that correspond to functional stages of maturation. First,
      cisternae at the cisternal assembly stage receive COPII vesicles from the ER and
      recycle components to the ER in COPI vesicles. At this stage, new cisternae are
      generated. Second, cisternae at the carbohydrate synthesis stage exchange
      material with one another via COPI vesicles. At this stage, most of the
      glycosylation and polysaccharide synthesis reactions occur. Third, cisternae at
      the carrier formation stage produce clathrin-coated vesicles and exchange
      material with endosomes. At this stage, biosynthetic cargo proteins are packaged
      into various transport carriers, and the cisternae ultimately disassemble.
      Discrete transitions occur as a cisterna matures from one stage to the next.
      Within each stage, the structure and composition of a cisterna can evolve, but
      the trafficking pathways remain unchanged. This model offers a unified framework
      for understanding the properties of the Golgi in diverse organisms. 

PMID- 23881166
TI  - [Periprosthetic humeral fracture: complex circumstances need critical selection
      of therapy].
AB  - Although periprosthetic humeral fractures were previously rare injuries, they
      will increase because of the rising life expectancy of patients and increasing
      implantation of shoulder prostheses. This article describes a case of an 86-year
      old female patient with very thin humeral cortex and a prosthesis filling the
      medullary cavity. The morphology of fractures and the surrounding circumstances
      determine choice of therapy. 

PMID- 23881167
TI  - A low-cost bio-inspired integrated carbon counter electrode for high conversion
      efficiency dye-sensitized solar cells.
AB  - A novel bio-inspired Pt- and FTO-free integrated pure carbon counter electrode
      (CE) for dye-sensitized solar cells (DSSCs) has been designed and fabricated
      using a porous carbon sheet as a conducting substrate and ordered mesoporous
      carbon (OMC) as the catalytic layer. A rigid, crustose lichen-like, integrated
      carbon-carbon composite architecture with a catalytic layer rooted in a porous
      conducting substrate was formed by a process of polymer precursor spin coating,
      infiltration and pyrolysis. The integrated pure carbon CE shows very low series
      resistance (R(s)), owing to the high conductivity of the carbon sheet (sheet
      resistance of 488 mOmega ?(-1)) and low charge-transfer resistance (R(ct)), due
      to the large specific surface area of the OMC layer that is accessible to the
      redox couple. The values of R(s) and R(ct) are much lower than those of a
      platinized fluorine-doped thin oxide glass (Pt/FTO) electrode. Cells with this CE
      show high solar-to-electricity conversion efficiencies (8.11%), comparable to
      that of Pt/FTO based devices (8.16%).

PMID- 23881168
TI  - Inhibition of Notch signaling induces extensive intussusceptive neo-angiogenesis
      by recruitment of mononuclear cells.
AB  - Notch is an intercellular signaling pathway related mainly to sprouting neo
      angiogenesis. The objective of our study was to evaluate the angiogenic
      mechanisms involved in the vascular augmentation (sprouting/intussusception)
      after Notch inhibition within perfused vascular beds using the chick area
      vasculosa and MxCreNotch1(lox/lox) mice. In vivo monitoring combined with
      morphological investigations demonstrated that inhibition of Notch signaling
      within perfused vascular beds remarkably induced intussusceptive angiogenesis
      (IA) with resultant dense immature capillary plexuses. The latter were
      characterized by 40 % increase in vascular density, pericyte detachment, enhanced
      vessel permeability, as well as recruitment and extravasation of mononuclear
      cells into the incipient transluminal pillars (quintessence of IA). Combination
      of Notch inhibition with injection of bone marrow-derived mononuclear cells
      dramatically enhanced IA with 80 % increase in vascular density and pillar number
      augmentation by 420 %. Additionally, there was down-regulation of ephrinB2 mRNA
      levels consequent to Notch inhibition. Inhibition of ephrinB2 or EphB4 signaling
      induced some pericyte detachment and resulted in up-regulation of VEGFRs but with
      neither an angiogenic response nor recruitment of mononuclear cells. Notably, Tie
      2 receptor was down-regulated, and the chemotactic factors SDF-1/CXCR4 were up
      regulated only due to the Notch inhibition. Disruption of Notch signaling at the
      fronts of developing vessels generally results in massive sprouting. On the
      contrary, in the already existing vascular beds, down-regulation of Notch
      signaling triggered rapid augmentation of the vasculature predominantly by IA.
      Notch inhibition disturbed vessel stability and led to pericyte detachment
      followed by extravasation of mononuclear cells. The mononuclear cells contributed
      to formation of transluminal pillars with sustained IA resulting in a dense
      vascular plexus without concomitant vascular remodeling and maturation.

PMID- 23881169
TI  - Erythropoietin is involved in the angiogenic potential of bone marrow macrophages
      in multiple myeloma.
AB  - Erythropoietin (Epo) is the crucial cytokine regulator of red blood cell
      production, and recombinant human erythropoietin (rHuEpo) is widely used in
      clinical practice for the treatment of anemia, primarily in kidney disease and in
      cancer. Increasing evidence suggests several biological roles for Epo and its
      receptor, Epo-R, unrelated to erythropoiesis, including angiogenesis. Epo-R has
      been found expressed in various non-haematopoietic cells and tissues, and in
      cancer cells. Here, we detected the expression of Epo-R in bone marrow-derived
      macrophages (BMMAs) from multiple myeloma (MM) and monoclonal gammopathy of
      undetermined significance (MGUS) patients and assessed whether Epo/Epo-R axis
      plays a role in MM macrophage-mediated angiogenesis. We found that Epo-R is over
      expressed in BMMAs from MM patients with active disease compared to MGUS
      patients. The treatment of BMMAs with rHuEpo significantly increased the
      expression and secretion of key pro-angiogenic mediators, such as vascular
      endothelial growth factor, hepatocyte growth factor and monocyte chemotactic
      protein (MCP-1/CCL-2), through activation of JAK2/STAT5 and PI3 K/Akt pathways.
      In addition, the conditioned media harvested from rHuEpo-treated BMMAs enhanced
      bone marrow-derived endothelial cell migration and capillary morphogenesis in
      vitro, and induced angiogenesis in the chorioallantoic membrane of chick embryos
      in vivo. Furthermore, we found an increase in the circulating levels of several
      pro-angiogenic cytokines in serum of MM patients with anemia under treatment with
      Epo. Our findings highlight the direct effect of rHuEpo on macrophage-mediated
      production of pro-angiogenic factors, suggesting that Epo/Epo-R pathway may be
      involved in the regulation of angiogenic response occurring in MM. 

PMID- 23881171
TI  - Lack of association of homocysteine concentrations with oxidative stress,
      alterations in carotid intima media thickness and endothelial reactivity in
      prepubertal children.
AB  - BACKGROUND AND AIMS: Our purpose was to assess the presence of risk factors for
      cardiovascular diseases (alterations in the lipid profile, fasting glycaemia,
      high arterial pressure values, oxidative stress, increased intima media thickness
      and impaired endothelium-dependent vasodilation) in prepubertal children with
      elevated homocysteine (Hcy) levels. METHODS: In a cross-sectional study, 35
      children with Hcy levels >=7.3 MUmol/l were matched by gender and age with 29
      children with Hcy levels <=4.1 MUmol/l. Our collected data included weight,
      height, waist circumference, systemic arterial pressure, lipid profile, fasting
      glycaemia and oxidative stress markers. A Doppler ultrasound was performed to
      measure the carotid intima media thickness and the endothelium-dependent
      vasodilation of the brachial artery. RESULTS: There were no statistically
      significant differences between the groups regarding the lipid profile and
      fasting glycaemia, blood pressure or oxidative stress. Overweight and obesity
      (body mass index z-score > +1) were more frequent in the group with Hcy >=7.3
      MUmol/l when compared to the group with Hcy <=4.1 MUmol/l [13/35 (37.1%) vs. 4/29
      (13.8%); p = 0.035]. After adjusting for nutritional status, there were no
      differences in the intima media thickness and endothelium-dependent vasodilation
      between children with high and low Hcy levels. CONCLUSIONS: Among the
      cardiovascular risk factors investigated in the present study, which was based on
      prepubertal children, only overweight and obesity were associated with increased
      Hcy concentrations (>=7.3 MUmol/l).

PMID- 23881172
TI  - An extensive candidate gene approach to speciation: diversity, divergence and
      linkage disequilibrium in candidate pigmentation genes across the European crow
      hybrid zone.
AB  - Colouration patterns have an important role in adaptation and speciation. The
      European crow system, in which all-black carrion crows and grey-coated hooded
      crows meet in a narrow hybrid zone, is a prominent example. The marked phenotypic
      difference is maintained by assortative mating in the absence of neutral genetic
      divergence, suggesting the presence of few pigmentation genes of major effect. We
      made use of the rich phenotypic and genetic resources in mammals and identified a
      comprehensive panel of 95 candidate pigmentation genes for birds. Based on
      functional annotation, we chose a subset of the most promising 37 candidates, for
      which we developed a marker system that demonstrably works across the avian
      phylogeny. In total, we sequenced 107 amplicons (~3 loci per gene, totalling 60
      kb) in population samples of crows (n=23 for each taxon). Tajima's D, Fu's FS,
      DHEW and HKA (Hudson-Kreitman-Aguade) statistics revealed several amplicons that
      deviated from neutrality; however, none of these showed significantly elevated
      differentiation between the two taxa. Hence, colour divergence in this system may
      be mediated by uncharacterized pigmentation genes or regulatory regions outside
      genes. Alternatively, the observed high population recombination rate
      (4Ner~0.03), with overall linkage disequilibrium dropping rapidly within the
      order of few 100 bp, may compromise the power to detect causal loci with nearby
      markers. Our results add to the debate as to the utility of candidate gene
      approaches in relation to genomic features and the genetic architecture of the
      phenotypic trait in question.

PMID- 23881174
TI  - Time-motion analysis and physiological responses to karate official combat
      sessions: is there a difference between winners and defeated karatekas?
AB  - PURPOSE: The aim of this study was to measure and compare physiological and time
      motion variables during karate fighting and to assess eventual differences
      between winners and defeated elite karatekas in an ecologically valid
      environment. METHODS: Fourteen elite male karatekas who regularly participated in
      national and international events took part in a national-level competition.
      RESULTS: There were no significant differences between winners and defeated
      karatekas regarding all the studied variables. Karatekas used more upper-limb
      (76.19%) than lower-limb techniques (23.80%). The kisami-zuki represented the
      most frequent technique, with 29.1% of all used techniques. The duration of each
      fighting activity ranged from <1 s to 5 s, with 83.8% +/- 12.0% of the actions
      lasting less than 2 s. Karatekas executed 17 +/- 7 high-intensity actions per
      fight, which corresponded to ~6 high-intensity actions per min. Action-to-rest
      ratio was about 1:1.5, and high-intensity-action- to-rest ratio was ~1:10. The
      mean blood lactate response at 3 min postcombat (Lapost) elicited during karate
      fighting was 11.18 +/- 2.21 mmol/L (difference between Lapre and Lapost = 10.01
      +/- 1.81 mmol/L). Mean heart rate (HR) was 177 +/- 14 beats/min (91% +/- 5% of
      HRpeak). Karatekas spent 65% of the time exercising at HR >90% of the individual
      HRpeak. CONCLUSION: Karatekas predominantly use upper-limb karate techniques.
      Karate's nature is intermittent, with fighting activities representing ~6% of
      total combat's duration and ~84% of actions lasting less than 2 s, with ~21-s
      mean time interval in between. Kumite combat sessions induced high La and near
      maximal cardiovascular strain. Other key success factors should be investigated
      to properly discriminate winners and defeated athletes.

PMID- 23881175
TI  - Lifestyle modification decreases arterial stiffness and plasma asymmetric
      dimethylarginine level in overweight and obese men.
AB  - BACKGROUND: Increased arterial stiffness is an independent risk factor for
      cardiovascular disease. Arterial stiffness is higher in obese individuals than in
      nonobese individuals. Lifestyle modifications (i.e. exercise and dietary
      modification) decrease arterial stiffness in obese individuals. Asymmetric
      dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase, an
      enzyme responsible for the generation of nitric oxide. AIM: The aim of this study
      was to examine whether lifestyle modifications affect circulating levels of ADMA
      in overweight and obese men and, if they do, whether ADMA is involved in the
      mechanism underlying the decrease in arterial stiffness with lifestyle
      modification. METHODS: Seventeen overweight and obese men (BMI: 29.8+/-0.8
      kg/m(2)) completed a 12-week lifestyle modification program, which included
      aerobic exercise and dietary modification. Before and after the intervention, we
      evaluated brachial-ankle pulse wave velocity (baPWV), an index of arterial
      stiffness, and plasma ADMA concentration in all participants. RESULTS: After the
      12-week lifestyle modification program, BMI and baPWV decreased significantly and
      the plasma ADMA concentration decreased markedly in overweight and obese men.
      There was a significant positive correlation between percent change in baPWV and
      plasma ADMA concentration. CONCLUSION: Lifestyle modifications reduce arterial
      stiffness and plasma ADMA concentration in overweight and obese individuals. A
      decrease in arterial stiffness was associated with a corresponding reduction in
      plasma ADMA concentrations. These results suggest that reductions in ADMA may be
      an important mechanism underlying the beneficial effect of lifestyle modification
      on arterial stiffness.

PMID- 23881177
TI  - Relative expressions of miR-205-5p, miR-205-3p, and miR-21 in tissues and serum
      of non-small cell lung cancer patients.
AB  - Objective was to assess and compare the relative expressions of miR-205-5p, miR
      205-3p, and miR-21-3p in tissues and serum among non-small cell lung carcinoma
      (NSCLC) patients, benign pulmonary conditions patients, and healthy volunteers.
      Serum samples were obtained between October 2011 and September 2012 from 20 NSCLC
      patients undergoing surgical treatment, 20 patients diagnosed with a benign lung
      disease (pulmonary tuberculosis, pneumonia, chronic obstructive pulmonary
      disease, or interstitial pneumonia) (lesion group), and 20 healthy volunteers
      (control group). NSCLC patients provided cancer tissues and cancer-adjacent
      normal tissues during surgery (paired specimens). Quantitative RT-PCR was used to
      assess miR-205-5p, miR-205-3p, and miR-21-3p expressions in serum and tissue
      samples. The relative expressions of miR-205-5p and miR-205-3p were significantly
      higher in NSCLC tissues compared with cancer-adjacent paired specimens (both P <
      0.001). In the serum, significantly higher miR-205-5p, miR-205-3p, and miR-21-3p
      relative expressions were observed in the NSCLC group compared with the two other
      groups (all P < 0.001). The relative expressions of miR-205-5p and miR-21-3p in
      NSCLC tissues and serum were significantly correlated (r = 0.553, P = 0.011; and
      r = -0.541, P = 0.014, respectively), while no significant correlation was
      observed for miR-205-3P (P = 0.120). Expressions of miR-205-5p and miR-205-3P in
      squamous cell carcinoma specimens were significantly higher than in lung
      adenocarcinoma specimens (both P = 0.001). Similarly, higher serum miR-205-5p and
      miR-205-3p levels were observed in squamous cell carcinoma patients (P = 0.033
      and P = 0.002, respectively). In this preliminary and novel study, miR-205-5p was
      more useful as a marker for NSCLC than miR-205-3p or miR-21, indicating a
      potential for future applications in NSCLC diagnosis and prognosis.

PMID- 23881179
TI  - Cervical epidural anesthesia is associated with increased cancer-free survival in
      laryngeal and hypopharyngeal cancer surgery: a retrospective propensity-matched
      analysis.
AB  - BACKGROUND AND OBJECTIVES: Regional anesthesia preserves perioperative immune
      competence and may reduce the risk of recurrence and metastasis after cancer
      surgery. Cervical epidural anesthesia provides adequate analgesia for head and
      neck cancer surgery, but its impact on cancer recurrence is unknown. METHODS:
      This study was a single-center retrospective cohort study of patients undergoing
      larynx or hypopharynx cancer surgery between January 1984 and December 2008. One
      hundred eleven patients had general anesthesia combined with intraoperative and
      postoperative cervical epidural; 160 had general anesthesia alone with
      postoperative morphine. From this cohort, matched pairs were selected using a
      propensity score to balance potential confounders of receiving epidural
      anesthesia. The primary end point was the length of cancer-free survival after
      surgery until September 2009. RESULTS: Propensity-based matching produced 65
      pairs. Matching was effective in achieving balance between groups for each of the
      preoperative variables collected. Combined epidural and general anesthesia (68% 5
      year cancer-free survival; 95% confidence interval [CI], 57%-82%) was associated
      with significantly increased cancer-free survival compared with general
      anesthesia alone (37% 5-year cancer-free survival; 95% CI, 25%-54%) with a
      corresponding adjusted hazard ratio of 0.49 (95% CI, 0.25-0.96; P = 0.04).
      Patients in the epidural group had an increased overall survival compared with
      the non-epidural group (P = 0.03). CONCLUSIONS: The association between cervical
      epidural anesthesia and increased cancer-free survival found in this
      retrospective study should be an important hypothesis to further investigate in
      head and neck cancer surgery.

PMID- 23881180
TI  - Fast and accurate automated cell boundary determination for fluorescence
      microscopy.
AB  - Detailed measurement of cell phenotype information from digital fluorescence
      images has the potential to greatly advance biomedicine in various disciplines
      such as patient diagnostics or drug screening. Yet, the complexity of cell
      conformations presents a major barrier preventing effective determination of cell
      boundaries, and introduces measurement error that propagates throughout
      subsequent assessment of cellular parameters and statistical analysis. State-of
      the-art image segmentation techniques that require user-interaction, prolonged
      computation time and specialized training cannot adequately provide the support
      for high content platforms, which often sacrifice resolution to foster the speedy
      collection of massive amounts of cellular data. This work introduces a strategy
      that allows us to rapidly obtain accurate cell boundaries from digital
      fluorescent images in an automated format. Hence, this new method has broad
      applicability to promote biotechnology. 

PMID- 23881181
TI  - Improved cathode for high efficient microbial-catalyzed reduction in microbial
      electrosynthesis cells.
AB  - Microbial electrosynthesis cells (MECs) are devices wherein microorganisms can
      electrochemically interact with electrodes, directly donating or accepting
      electrons from electrode surfaces. Here, we developed a novel cathode by using
      nickel nanowires anchored to graphite for the improvement of microbial-catalyzed
      reduction in MEC cathode chamber. This porous nickel-nanowire-network-coated
      graphite electrode increased the interfacial area and interfacial interactions
      between the cathode surface and the microbial biofilm. A 2.3 fold increase in bio
      reduction rate over the untreated graphite was observed. Around 282 mM day(-1) m(
      2) of acetate resulting from the bio-reduction of carbon dioxide by Sporomusa was
      produced with 82 +/- 14% of the electrons consumed being recovered in acetate. 

PMID- 23881182
TI  - Self-catalyzed VLS grown InAs nanowires with twinning superlattices.
AB  - We report on the self-catalyzed growth of InAs nanowires by molecular beam
      epitaxy on GaAs substrates covered by a thin silicon oxide layer. Clear evidence
      is presented to demonstrate that, under our experimental conditions, the growth
      takes place by the vapor-liquid-solid (VLS) mechanism via an In droplet. The
      nanowire growth rate is controlled by the arsenic pressure while the diameter
      depends mainly on the In rate. The contact angle of the In droplet is smaller
      than that of the Ga droplet involved in the growth of GaAs nanowires, resulting
      in much lower growth rates. The crystal structure of the VLS grown InAs nanowires
      is zinc blende with regularly spaced rotational twins forming a twinning
      superlattice. 

PMID- 23881183
TI  - Both hair cortisol levels and perceived stress predict increased symptoms of
      depression: an exploratory study in young adults.
AB  - OBJECTIVE: Depressive symptoms are a common mental health problem among young
      adults, but the physiological mechanisms that mediate between stress and
      depressive symptoms remain unclear. Accordingly, this exploratory study (1)
      examined how hair cortisol concentrations were associated with self-perceived
      stress and depressive symptoms in a sample of young adults and (2) tested whether
      hair cortisol could explain variance in depressive symptoms beyond perceived
      stress before and after controlling for levels of vigorous physical activity
      (VPA). METHODS: The sample consisted of 42 exercise and health science university
      students (20 males, 22 females; mean age = 21.2 years). Cortisol concentrations
      were extracted from hair strands close to the scalp. Participants completed self
      rating questionnaires about depressive symptoms and perceived stress. RESULTS:
      Students with elevated hair cortisol levels tended to report lower depressive
      symptoms and lower perceived stress. Increased perceived stress was associated
      with higher depressive symptoms, and both hair cortisol and perceived stress
      predicted depressive symptoms after controlling for VPA. CONCLUSIONS: The present
      data suggest that elevated hair cortisol levels do not necessarily constitute a
      health risk. Hair cortisol measurement can serve as a noninvasive and painless
      biomarker of chronic stress and mental disorders; however, additional research is
      needed.

PMID- 23881184
TI  - Comparison of escitalopram and paroxetine in the treatment of major depressive
      disorder.
AB  - This is a single-blind, parallel, flexible-dose study to compare the efficacy and
      tolerability of escitalopram and paroxetine in the treatment of patients with
      major depressive disorder. We recruited 399 patients from the outpatient clinics
      of five hospitals in northern Taiwan. Patients were administered either
      escitalopram (10-30 mg) or paroxetine (20-40 mg) according to the judgment of
      clinicians. These patients were assessed using the Hamilton Rating Scale for
      Depression (HAM-D) and the Hamilton Rating Scale for Anxiety at weeks 0, 1, 2, 4,
      6, and 8. A total of 302 patients fulfilled the evaluation criteria and were
      included in a statistical analysis. We found that escitalopram induced more
      significant symptom reduction and response rate in terms of the mean HAM-D scores
      at week 6 (P<0.05) and week 8 (P<0.05) than paroxetine, but that there were no
      significant differences between the two groups in the remission rate.
      Escitalopram induced significantly less frequency of adverse effects of weakness
      (P<0.01), nausea and vomiting (P<0.001), drowsiness (P<0.01) as well as
      somnolence (P<0.01) than paroxetine, although all these side effects were mild
      and tolerable. However for a more definitive result, future prospective trials
      with the inclusion of a placebo group and a double-blind design are needed. In
      patients who did not have severe depression (HAM-D score at baseline<21), but not
      in severely depressed patients, escitalopram was statistically superior to
      paroxetine, as shown by the mean change in the HAM-D score. 

PMID- 23881185
TI  - Efficacy of desvenlafaxine 50 mg compared with placebo in patients with moderate
      or severe major depressive disorder: a pooled analysis of six randomized, double
      blind, placebo-controlled studies.
AB  - This study assessed the efficacy of desvenlafaxine 50 mg/day compared with
      placebo for treating moderate or severe major depressive disorder (MDD). Data
      were pooled from six double-blind, placebo-controlled, desvenlafaxine 50 mg/day
      fixed-dose studies in adults with MDD. The primary endpoint was improvement in 17
      item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline at week
      8. HAM-D17 changes were evaluated in patients with moderate (18<HAM-D17<25) or
      severe (HAM-D17>=25) MDD at baseline using analysis of covariance with treatment,
      study, and baseline in the model. The pooled analysis included 2189 patients
      (desvenlafaxine 50 mg, n=1150; placebo, n=1039). Of those, 694 (32%) patients had
      severe depression at baseline. Desvenlafaxine improved HAM-D17 scores versus
      placebo in patients with either moderate [desvenlafaxine, adjusted mean (+/-SE), 
      10.26+/-0.24; placebo, -8.87+/-0.26; P<0.001] or severe MDD (desvenlafaxine, 
      11.91+/-0.40; placebo, -9.85+/-0.42; P<0.001). Both moderately and severely
      depressed patients had significantly higher rates of response and remission with
      desvenlafaxine treatment compared with placebo (all P's<=0.029). Results were
      similar when baseline severity was defined by Montgomery-Asberg Depression Rating
      Scale or Sheehan Disability Scale scores. Desvenlafaxine 50 mg/day significantly
      improved depressive symptoms regardless of severity at baseline and was effective
      in treating both moderate and severe MDD. 

PMID- 23881186
TI  - Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin
      dependent protein kinase II in normal and hypertrophied hearts.
AB  - Increased adult cardiac fibroblast proliferation results in an increased collagen
      deposition responsible for the fibrosis accompanying pathological remodelling of
      the heart. The mechanisms regulating cardiac fibroblast proliferation remain
      poorly understood. Using a minimally invasive transverse aortic banding (MTAB)
      mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac
      fibroblast proliferation. We have investigated whether calcium/calmodulin
      dependent protein kinase IIdelta (CaMKIIdelta) regulates proliferation in
      fibroblasts isolated from normal and hypertrophied hearts. It is known that
      CaMKIIdelta plays a central role in cardiac myocyte contractility, but nothing is
      known of its role in adult cardiac fibroblast function. The MTAB model used here
      produces extensive hypertrophy and fibrosis. CaMKIIdelta protein expression and
      activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts
      isolated from hypertrophied hearts. In response to angiotensin II, cardiac
      fibroblasts isolated from MTAB hearts show increased proliferation rates.
      Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation
      in cells isolated from both sham and MTAB hearts, with a significantly greater
      effect evident in MTAB cells. These results are the first to show selective
      upregulation of CaMKIIdelta in adult cardiac fibroblasts following cardiac
      hypertrophy and to assign a previously unrecognised role to CaMKII in regulating
      adult cardiac fibroblast function in normal and diseased hearts. 

PMID- 23881187
TI  - A peer-educator network HIV prevention intervention among injection drug users:
      results of a randomized controlled trial in St. Petersburg, Russia.
AB  - We evaluated the efficacy of a peer-educator network intervention as a strategy
      to reduce HIV acquisition among injection drug users (IDUs) and their drug and/or
      sexual networks. A randomized controlled trial was conducted in St. Petersburg,
      Russia among IDU index participants and their risk network participants. Network
      units were randomized to the control or experimental intervention. Only the
      experimental index participants received training sessions to communicate risk
      reduction techniques to their network members. Analysis includes 76 index and 84
      network participants who were HIV uninfected. The main outcome measure was HIV
      sero-conversion. The incidence rates in the control and experimental groups were
      19.57 (95 % CI 10.74-35.65) and 7.76 (95 % CI 3.51-17.19) cases per 100 p/y,
      respectively. The IRR was 0.41 (95 % CI 0.15-1.08) without a statistically
      significant difference between the two groups (log rank test statistic X(2) =
      2.73, permutation p value = 0.16). Retention rate was 67 % with a third of the
      loss due to incarceration or death. The results show a promising trend that this
      strategy would be successful in reducing the acquisition of HIV among IDUs. 

PMID- 23881189
TI  - Hypothalamic inflammation: marker or mechanism of obesity pathogenesis?

PMID- 23881191
TI  - ON NO--the continuing story of nitric oxide, diabetes, and cardiovascular
      disease.

PMID- 23881190
TI  - Remodeling of lipid metabolism by dietary restriction of essential amino acids.

PMID- 23881192
TI  - Potassium channels, renal fibrosis, and diabetes.

PMID- 23881193
TI  - Metabolomics reveals unexpected responses to oral glucose.

PMID- 23881194
TI  - Insulin and sympathoexcitation: it is not all in your head.

PMID- 23881195
TI  - Adipose tissue macrophages are innate to the immunological awareness of adipose
      tissue.

PMID- 23881196
TI  - Therapeutic targeting of B cells and T cells in autoimmune diabetes: is it a
      solution?

PMID- 23881197
TI  - Frail HDLs and stiff arteries in type 2 diabetes in juveniles.

PMID- 23881198
TI  - Epac2A makes a new impact in beta-cell biology.

PMID- 23881199
TI  - Diagnostic assessment of diabetic gastroparesis.

PMID- 23881203
TI  - Comment on: Allister et al. UCP2 regulates the glucagon response to fasting and
      starvation. Diabetes 2013;62:1623-1633.

PMID- 23881200
TI  - Evidence for rapamycin toxicity in pancreatic beta-cells and a review of the
      underlying molecular mechanisms.
AB  - Rapamycin is used frequently in both transplantation and oncology. Although
      historically thought to have little diabetogenic effect, there is growing
      evidence of beta-cell toxicity. This Review draws evidence for rapamycin toxicity
      from clinical studies of islet and renal transplantation, and of rapamycin as an
      anticancer agent, as well as from experimental studies. Together, these studies
      provide evidence that rapamycin has significant detrimental effects on beta-cell
      function and survival and peripheral insulin resistance. The mechanism of action
      of rapamycin is via inhibition of mammalian target of rapamycin (mTOR). This
      Review describes the complex mTOR signaling pathways, which control vital
      cellular functions including mRNA translation, cell proliferation, cell growth,
      differentiation, angiogenesis, and apoptosis, and examines molecular mechanisms
      for rapamycin toxicity in beta-cells. These mechanisms include reductions in beta
      cell size, mass, proliferation and insulin secretion alongside increases in
      apoptosis, autophagy, and peripheral insulin resistance. These data bring into
      question the use of rapamycin as an immunosuppressant in islet transplantation
      and as a second-line agent in other transplant recipients developing new-onset
      diabetes after transplantation with calcineurin inhibitors. It also highlights
      the importance of close monitoring of blood glucose levels in patients taking
      rapamycin as an anticancer treatment, particularly those with preexisting glucose
      intolerance. 

PMID- 23881204
TI  - Response to Comment on: Allister et al. UCP2 regulates the glucagon response to
      fasting and starvation. Diabetes 2013;62:1623-1633.

PMID- 23881205
TI  - Comment on: Korpos et al. The peri-islet basement membrane, a barrier to
      infiltrating leukocytes in type 1 diabetes in mouse and human. Diabetes
      2013;62:531-542.

PMID- 23881206
TI  - Response to comment on: Korpos et al. The peri-islet basement membrane, a barrier
      to infiltrating leukocytes in type 1 diabetes in mouse and human. Diabetes
      2013;62:531-542.

PMID- 23881207
TI  - A standard error: distinguishing standard deviation from standard error.

PMID- 23881208
TI  - Using temporal modulation sensitivity to select stimulation sites for processor
      MAPs in cochlear implant listeners.
AB  - Previous studies in our laboratory showed that temporal acuity as assessed by
      modulation detection thresholds (MDTs) varied across activation sites and that
      this site-to-site variability was subject specific. Using two 10-channel MAPs,
      the previous experiments showed that processor MAPs that had better across-site
      mean (ASM) MDTs yielded better speech recognition than MAPs with poorer ASM MDTs
      tested in the same subject. The current study extends our earlier work on
      developing more optimal-fitting strategies to test the feasibility of using a
      site-selection approach in the clinical domain. This study examined the
      hypothesis that revising the clinical speech processor MAP for cochlear implant
      (CI) recipients by turning off selected sites that have poorer temporal acuity
      and reallocating frequencies to the remaining electrodes would lead to improved
      speech recognition. Twelve CI recipients participated in the experiments. We
      found that site selection procedure based on MDTs in the presence of a masker
      resulted in improved performance on consonant recognition and recognition of
      sentences in noise. In contrast, vowel recognition was poorer with the
      experimental MAP than with the clinical MAP, possibly due to reduced spectral
      resolution when sites were removed from the experimental MAP. Overall, these
      results suggest a promising path for improving recipient outcomes using
      personalized processor-fitting strategies based on a psychophysical measure of
      temporal acuity.

PMID- 23881209
TI  - Endothelial protein C receptor polymorphisms and risk of severe sepsis in
      critically ill patients.
AB  - PURPOSE: Endothelial protein C receptor (EPCR) is expressed mainly in endothelial
      cells and is involved in regulation of the cytoprotective and anticoagulant
      pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the
      risk of severe sepsis and/or septic shock (SS/SS) development in critically ill
      patients. METHODS: Three polymorphisms in the EPCR gene were genotyped in 389
      Caucasian critically ill patients, hospitalized in the intensive care units of
      two major hospitals in Athens, Greece. Multivariate logistic regression analysis
      controlling for age, acute physiology and chronic health evaluation (APACHE) II
      and sequential organ failure assessment (SOFA) scores, sex, and diagnosis was
      performed to determine the effect of haplotypes H1 and H3 in the EPCR gene on the
      development of SS/SS. RESULTS: H2 carriers versus all other genotypes combined
      had a nonsignificant excess of SS/SS (p = 0.087). SS/SS occurred in 38.8% of
      critically ill patients carrying minor alleles belonging to both H1 and H3
      haplotypes, in 58.0% of H1 carriers, 64.3% of H3 carriers, and 65.2% of patients
      carrying all common alleles (H2). Compared with H2 carriers, the odds ratios (OR)
      for developing SS/SS were 0.34 [95% confidence interval (CI) 0.16-0.76, p =
      0.008] for simultaneous H1 and H3 carriers, 0.65 (95% CI 0.37-1.13, p = 0.123)
      for H1 carriers, and 0.82 (95 % CI 0.39-1.70, p = 0.590) for H3 carriers.
      CONCLUSIONS: Our results indicate that simultaneous carriers of minor alleles
      belonging to both the H1 and H3 haplotypes may be at reduced risk of developing
      SS/SS in this cohort of critically ill patients.

PMID- 23881210
TI  - Thrombocytopenia in the critically ill: considering pathophysiology rather than
      looking for a magic threshold.

PMID- 23881211
TI  - The membrane transport and polyglutamation of pralatrexate: a new-generation
      dihydrofolate reductase inhibitor.
AB  - PURPOSE: To characterize, directly and for the first time, the membrane transport
      and metabolism of pralatrexate, a new-generation dihydrofolate reductase
      inhibitor approved for the treatment for peripheral T-cell lymphoma. EXPERIMENTAL
      DESIGN: [(3)H]pralatrexate transport was studied in unique HeLa cell lines that
      express either the reduced folate carrier (RFC) or the proton-coupled folate
      transporter (PCFT). Metabolism to active polyglutamate derivatives was assessed
      by liquid chromatography. These properties were compared to those of methotrexate
      (MTX). RESULTS: The pralatrexate influx K t, mediated by RFC, the major route of
      folate/antifolate transport at systemic pH, was 0.52 MUMU, 1/10th the MTX influx
      K i. The electrochemical potential of pralatrexate within HeLa cells far exceeded
      the extracellular level and was greater than for MTX. In contrast, MTX transport
      mediated by PCFT, the mechanism of folate/antifolate absorption in the small
      intestine, exceeded that for pralatrexate. After a 6 h exposure of HeLa cells to
      0.5 MUM pralatrexate, 80 % of intracellular drug was its active polyglutamate
      forms, predominantly the tetraglutamate, and was suppressed when cells were
      loaded with natural folates. There was negligible formation of MTX
      polyglutamates. The difference in pralatrexate and MTX growth inhibition was far
      greater after transient exposures (375-fold) than continuous exposure (25-fold)
      to the drugs. CONCLUSIONS: Pralatrexate's enhanced activity relative to MTX is
      due to its much more rapid rate of transport and polyglutamation, the former less
      important when the carrier is saturated. The low affinity of pralatrexate for
      PCFT predicts a lower level of enterohepatic circulation and increased fecal
      excretion of the drug relative to MTX.

PMID- 23881212
TI  - CPT-11 as a second-line treatment for patients with advanced/metastatic gastric
      cancer who failed S-1 (CCOG0702).
AB  - BACKGROUND: In Japan, CPT-11 is often used to treat unresectable gastric cancer
      in the second-line setting. However, evidence regarding benefit of second-line
      chemotherapy remains sparse, especially after failing S-1. METHODS: A phase II
      study to evaluate the efficacy and safety of weekly administration of CPT-11 at a
      dose of 100 mg/m(2) after failing a S-1-containing first-line treatment was
      planned with response rate as a primary end point. UGT1A1*6, *27, and *28
      genotyping were performed in all cases, and those found to have either homozygous
      for *28, homozygous for *6, heterozygous for both *6 and *28, and heterozygous
      for *27 were rendered ineligible for the phase II trial. RESULTS: Two patients of
      homozygous for *28, two patients of homozygous for *6, and one patient of
      heterozygous for *27 were found among 39 recruited patients. The median number of
      courses delivered was 3 courses. The overall response rate was 15.4 % and disease
      control rate was 65.4 %. The median time to treatment failure was 87.5 days and
      median overall survival was 268 days. Twenty-two (73 %) of 30 valuable patients
      experienced protocol-specified skip of treatment and 8 (30 %) of patients could
      continue treatment with dose reduction. >=G3 neutropenia was found in 30 % and
      >=G3 anorexia and diarrhea were found in 23 and 17 %, respectively. CONCLUSION:
      Weekly CPT-11 at 100 mg/m(2) showed moderate response among gastric cancer
      patients who were refractory to S-1, but the disease control rate seemed
      meaningful. Even after selection of patients by UGT1A1 polymorphism of *6, *27,
      and *28, severe toxic events could not be prevented completely.

PMID- 23881213
TI  - The small-molecule TNF-alpha inhibitor, UTL-5g, delays deaths and increases
      survival rates for mice treated with high doses of cisplatin.
AB  - PURPOSE: UTL-5g is a novel small-molecule chemoprotector that lowers
      hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through
      TNF-alpha inhibition among other factors. The objective of this study was to
      investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and
      increase cisplatin tolerability in mice. MATERIALS AND METHODS: BDF1 female mice
      were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at
      60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg,
      respectively, on Day 0. Starting from Day 1, individual mice were again treated
      daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body
      weights were monitored. RESULTS: UTL-5g treatment increased the survival rate and
      delayed the time to death for mice treated with 150 % of the maximum tolerated
      dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin
      (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time
      to death. Treatment of UTL-5g did not have a significant effect on weight loss
      induced by cisplatin, indicating that body weight may not be a sensitive-enough
      measure for chemoprotection of UTL-5g against cisplatin. CONCLUSIONS: In summary,
      UTL-5g delayed deaths and increased survival rates of mice treated by high doses
      of cisplatin, indicating that UTL-5g is capable of reducing the overall acute
      toxicity of cisplatin and increased cisplatin tolerability in mice; this is in
      line with the specific chemoprotective effects of UTL-5g previously reported.
      Further investigation of UTL-5g in combination with cisplatin is warranted.

PMID- 23881215
TI  - New chaetoglobosin derivatives, MBJ-0038, MBJ-0039 and MBJ-0040, isolated from
      the fungus Chaetomium sp. f24230.

PMID- 23881216
TI  - Modification of charge transfer in a two-dimensional donor/acceptor framework by
      the insertion of another donor-type molecule into electronegative interlayer
      pockets.
AB  - Pyrene-intercalated layered compounds, [{Ru2(O2CCF3)4}2(TCNQR(x))].2(pyrene)
      (TCNQR(x) = 7,7,8,8-tetracyano-p-quinodimethane derivatives; R(x) = H4 and F4),
      were synthesized. Pyrene prohibits intralayer electron transfer of [Ru2(II,II)] 
      > TCNQR(x), even in the compound with R(x) = F4, from occurring.

PMID- 23881217
TI  - Design, synthesis and in vitro kinetic study of tranexamic acid prodrugs for the
      treatment of bleeding conditions.
AB  - Based on density functional theory (DFT) calculations for the acid-catalyzed
      hydrolysis of several maleamic acid amide derivatives four tranexamic acid
      prodrugs were designed. The DFT results on the acid catalyzed hydrolysis revealed
      that the reaction rate-limiting step is determined on the nature of the amine
      leaving group. When the amine leaving group was a primary amine or tranexamic
      acid moiety, the tetrahedral intermediate collapse was the rate-limiting step,
      whereas in the cases by which the amine leaving group was aciclovir or cefuroxime
      the rate-limiting step was the tetrahedral intermediate formation. The linear
      correlation between the calculated DFT and experimental rates for N
      methylmaleamic acids 1-7 provided a credible basis for designing tranexamic acid
      prodrugs that have the potential to release the parent drug in a sustained
      release fashion. For example, based on the calculated B3LYP/6-31G(d,p) rates the
      predicted t1/2 (a time needed for 50 % of the prodrug to be converted into drug)
      values for tranexamic acid prodrugs ProD 1-ProD 4 at pH 2 were 556 h [50.5 h as
      calculated by B3LYP/311+G(d,p)] and 6.2 h as calculated by GGA: MPW1K), 253 h, 70
      s and 1.7 h, respectively. Kinetic study on the interconversion of the newly
      synthesized tranexamic acid prodrug ProD 1 revealed that the t1/2 for its
      conversion to the parent drug was largely affected by the pH of the medium. The
      experimental t1/2 values in 1 N HCl, buffer pH 2 and buffer pH 5 were 54 min,
      23.9 and 270 h, respectively. 

PMID- 23881218
TI  - Occupational exposure to trichloroethylene and risk of non-Hodgkin lymphoma and
      its major subtypes: a pooled InterLymph [correction of IinterLlymph] analysis.
AB  - OBJECTIVES: We evaluated the association between occupational exposure to
      trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled
      analysis of four international case-control studies. METHODS: Overall, the pooled
      study population included 3788 NHL cases and 4279 controls. Risk of NHL and its
      major subtypes associated with TCE exposure was calculated with unconditional
      logistic regression and polytomous regression analysis, adjusting by age, gender
      and study. RESULTS: Risk of follicular lymphoma (FL), but not NHL overall or
      other subtypes, increased by probability (p=0.02) and intensity level (p=0.04),
      and with the combined analysis of four exposure metrics assumed as independent
      (p=0.004). After restricting the analysis to the most likely exposed study
      subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were
      elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01,
      respectively) and with the combined analysis of duration, frequency and intensity
      of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small
      numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B
      cell lymphoma, FL and CLL, showed increases in risk ranging 2-3.2-fold in the
      highest category of exposure intensity. No significant heterogeneity in risk was
      detected by major NHL subtypes or by study. CONCLUSIONS: Our pooled analysis
      apparently supports the hypothesis of an increase in risk of specific NHL
      subtypes associated with occupational exposure to TCE.

PMID- 23881219
TI  - Multiple metal exposures and renal effect: their magnitude of contribution.

PMID- 23881221
TI  - Performance enhancement of metal-oxide-semiconductor tunneling temperature
      sensors with nanoscale oxides by employing ultrathin Al2O3 high-k dielectrics.
AB  - We demonstrated a promising route for enhancing temperature sensitivity,
      improving saturation voltage, and reducing power consumption of the MOS(p)
      tunneling temperature sensors by introducing ultrathin Al2O3 into the dielectric
      stacks. Detailed illustrations of the working mechanism and device concept are
      given in this work. Three kinds of MOS(p) tunneling temperature sensors with
      nanoscale SiO2, HfO2, and Al2O3 dielectrics were compared comprehensively. For
      Al2O3 MOS(p) devices with an equivalent oxide thickness of 2 nm, the sensing
      performance was effectively improved and the temperature-sensitive current
      voltage characteristics are reliable and reproducible. The low-temperature
      processing Al2O3 MOS(p) tunneling temperature sensors are potential candidates
      for temperature monitoring sensors on chips or biomedical systems under low
      thermal budget processing consideration. 

PMID- 23881220
TI  - Metal-drug synergy: new ruthenium(II) complexes of ketoconazole are highly active
      against Leishmania major and Trypanosoma cruzi and nontoxic to human or murine
      normal cells.
AB  - In our ongoing search for new metal-based chemotherapeutic agents against
      leishmaniasis and Chagas disease, six new ruthenium-ketoconazole (KTZ) complexes
      have been synthesized and characterized, including two octahedral coordination
      complexes-cis,fac-[Ru(II)Cl2(DMSO)3(KTZ)] (1) and cis
      [Ru(II)Cl2(bipy)(DMSO)(KTZ)] (2) (where DMSO is dimethyl sulfoxide and bipy is
      2,2'-bipyridine)-and four organometallic compounds-[Ru(II)(eta(6)-p
      cymene)Cl2(KTZ)] (3), [Ru(II)(eta(6)-p-cymene)(en)(KTZ)][BF4]2 (4),
      [Ru(II)(eta(6)-p-cymene)(bipy)(KTZ)][BF4]2 (5), and [Ru(II)(eta(6)-p
      cymene)(acac)(KTZ)][BF4] (6) (where en is ethylenediamine and acac is
      acetylacetonate); the crystal structure of 3 is described. The central hypothesis
      of our work is that combining a bioactive compound such as KTZ and a metal in a
      single molecule results in a synergy that can translate into improved activity
      and/or selectivity against parasites. In agreement with this hypothesis,
      complexation of KTZ with Ru(II) in compounds 3-5 produces a marked enhancement of
      the activity toward promastigotes and intracellular amastigotes of Leishmania
      major, when compared with uncomplexed KTZ, or with similar ruthenium compounds
      not containing KTZ. Importantly, the selective toxicity of compounds 3-5 toward
      the leishmania parasites, in relation to human fibroblasts and osteoblasts or
      murine macrophages, is also superior to the selective toxicities of the
      individual constituents of the drug. When tested against Trypanosoma cruzi
      epimastigotes, some of the organometallic complexes displayed activity and
      selectivity comparable to those of free KTZ. A dual-target mechanism is suggested
      to account for the antiparasitic properties of these complexes.

PMID- 23881222
TI  - A lab-in-a-droplet bioassay strategy for centrifugal microfluidics with density
      difference pumping, power to disc and bidirectional flow control.
AB  - In this paper, we present a lab-in-a-droplet bioassay strategy for a centrifugal
      microfluidics or lab-on-a-disc (LOAD) platform with three important advancements
      including density difference pumping, power to disc and bidirectional flow
      control. First, with the water based bioassay droplets trapped in a micro-channel
      filled with mineral oil, centrifugal force due to the density difference between
      the water and oil phases actuates droplet movement while the oil based medium
      remains stationary. Second, electricity is coupled to the rotating disc through a
      split-core transformer, thus enabling on-chip real-time heating in selected areas
      as desired and wireless programmable functionality. Third, an inertial mechanical
      structure is proposed to achieve bidirectional flow control within the spinning
      disc. The droplets can move back and forth between two heaters upon changing the
      rotational speed. Our platform is an essential and versatile solution for
      bioassays such as those involving DNA amplification, where localized temperature
      cycling is required. Finally, without the loss of generality, we demonstrate the
      functionality of our platform by performing real-time polymerase chain reaction
      (RT-PCR) in a linear microchannel made with PTFE (Teflon) micro-tubing. 

PMID- 23881223
TI  - HIV enteropathy: HAART reduces HIV-induced stem cell hyperproliferation and crypt
      hypertrophy to normal in jejunal mucosa.
AB  - OBJECTIVE: To analyse the structural and kinetic response of small intestinal
      crypt epithelial cells including stem cells to highly active antiretroviral
      therapy (HAART). DESIGN: Crypt size and proliferative activity of transit and
      stem cells in jejunal mucosa were quantified using morphometric techniques.
      METHODS: Crypt length was measured by counting the number of enterocytes along
      one side of a number of crypts in each biopsy specimen and the mean crypt length
      was calculated. Proliferating crypt cells were identified with MIB-1 monoclonal
      antibody, and the percentage of crypt cells in proliferation was calculated at
      each cell position along the length of the crypt (proliferation index). Data were
      obtained from 9 HIV-positive test patients co-infected with microsporidia, 34 HIV
      positive patients receiving HAART and 13 control cases. RESULTS: Crypt length was
      significantly greater in test patients than in controls, but crypt length in
      patients receiving HAART was normal. The proliferation index was greater in test
      subjects than in controls in stem and transit cell compartments, and was
      decreased in patients treated with HAART only in the stem cell region of the
      crypt. CONCLUSIONS: Villous atrophy in HIV enteropathy is attributed to crypt
      hypertrophy and encroachment of crypt cells onto villi. HAART restores normal
      crypt structure by inhibition of HIV-driven stem cell hyperproliferation at the
      crypt bases.

PMID- 23881224
TI  - Hypersensitivity pneumonitis: a review and update of histologic findings.
AB  - Hypersensitivity pneumonitis (HSP) is a poorly understood entity typically caused
      by exposure to an inciting antigen such as fungi, thermophilic bacteria or animal
      protein. Clinically, HSP is often divided into acute, subacute and chronic forms.
      While the subacute form is best described from a pathologic standpoint, the
      pathology of chronic HSP has only been critically evaluated in the past decade
      and the pathology of acute HSP is poorly described. The aim of this review is to
      summarise the current knowledge of pathogenetic theories of HSP and to review the
      current knowledge of the pathology of each stage of HSP and the main entities in
      the differential diagnosis. 

PMID- 23881225
TI  - Exudative retinal detachment following photocoagulation in older premature
      infants for retinopathy of prematurity: description and management.
AB  - PURPOSE: To describe exudative retinal detachment following laser
      photocoagulation after 40 weeks of postmenstrual age (PMA) for retinopathy of
      prematurity in premature infants, its medical management, and outcomes. METHODS:
      Two pediatric vitreoretinal surgeons at 2 different quaternary care institutions
      retrospectively identified children who received laser photocoagulation after 40
      weeks of PMA and subsequently developed exudative detachment. Hospital course,
      management, and outcomes were identified. RESULTS: Three infants were identified
      that developed exudative retinal detachments following laser photocoagulation for
      retinopathy of prematurity after 40 weeks of PMA. The average gestational age was
      25 weeks with an average birth weight of 650 g. All babies were Zone II at
      initial examination and developed Stage 3 with pre-plus or plus disease after 40
      weeks of PMA (average 42 weeks of PMA). Therapy consisted of topical cyclogyl
      (0.5%) and topical prednisolone acetate (1%) to the affected eyes and intravenous
      dexamethasone in all cases. The exudative retinal detachments resolved by 50
      weeks of PMA in all infants. Hard exudates following resolution were found in all
      eyes. Two eyes demonstrated temporal macular dragging. CONCLUSION: Premature
      infants who require laser photocoagulation for retinopathy of prematurity at >40
      weeks of PMA may be predisposed to develop exudative retinal detachments. In the
      absence of identifiable traction, systemic corticosteroid use can be considered
      to achieve favorable anatomic outcomes.

PMID- 23881226
TI  - Oct-based interpretation of the vitreomacular interface and indications for
      pharmacologic vitreolysis.
AB  - PURPOSE: To review the role of optical coherence tomography (OCT) in diagnosis
      and management of vitreomacular disease and the impact of OCT on potential uses
      of ocriplasmin, a new pharmacologic vitreolysis agent recently approved by the
      U.S. Food and Drug Administration for the treatment of symptomatic vitreomacular
      adhesion. METHODS: Analysis of current literature regarding OCT in diagnosis and
      management of vitreomacular interface disease. RESULTS: Posterior vitreous
      detachment is typically a nonpathologic age-related event. Anomalous posterior
      vitreous detachment emerges when the vitreous cortex fails to cleanly detach from
      the macula, optic nerve, or other adherent sites. Focal vitreomacular adhesion is
      a nonpathologic anatomical designation associated with perifoveal posterior
      vitreous detachment but normal retinal morphology on OCT. Vitreomacular traction
      is a pathologic consequence of persistent vitreous attachment with structural
      disturbance of the macular retina visible on OCT. Full-thickness macular holes
      are foveal defects continuous through all retinal layers to the retinal pigment
      epithelium. Vitreomacular traction and macular hole with focal vitreomacular
      adhesion are indications for pharmacologic vitreolysis. CONCLUSION: Noninvasive
      high-resolution OCT imaging has transformed the understanding of vitreomacular
      interface disease. Careful evaluation of the vitreomacular interface with OCT has
      increased in importance with the introduction of ocriplasmin for vitreomacular
      adhesion associated with symptomatic anatomical retinal changes.

PMID- 23881227
TI  - Possible role for fundus autofluorescence as a predictive factor for visual
      acuity recovery after epiretinal membrane surgery.
AB  - PURPOSE: To study the potential association between fundus autofluorescence,
      spectral-domain optical coherence tomography, and visual acuity in patients
      undergoing surgery because of epiretinal membranes. METHODS: Prospective,
      interventional case series including 26 patients submitted to vitrectomy because
      of symptomatic epiretinal membranes. Preoperative evaluation consisted of a
      complete ophthalmologic examination, autofluorescence, and spectral-domain
      optical coherence tomography. Studied variables included foveal autofluorescence
      (fov.AF), photoreceptor inner segment/outer segment (IS/OS) junction line
      integrity, external limiting membrane integrity, central foveal thickness, and
      foveal morphology. All examinations were repeated at the first, third, and sixth
      postoperative months. The main outcome measures were logarithm of minimal angle
      resolution visual acuity, fov.AF integrity, and IS/OS integrity. RESULTS: All
      cases showing a continuous IS/OS line had an intact fov.AF, whereas patients with
      IS/OS disruption could have either an increased area of foveal
      hypoautofluorescence or an intact fov.AF, with the latter being associated with
      IS/OS integrity recovery in follow-up spectral-domain optical coherence
      tomography imaging. The only preoperative variables presenting a significant
      correlation with final visual acuity were baseline visual acuity (P = 0.047) and
      fov.AF grade (P = 0.023). CONCLUSION: Recovery of IS/OS line integrity after
      surgery, in patients with preoperative IS/OS disruption and normal fov.AF, can be
      explained by the presence of a functional retinal pigment epithelium
      photoreceptor complex, supporting normal photoreceptor activity. Autofluorescence
      imaging provides a functional component to the study of epiretinal membranes,
      complementing the structural information obtained with optical coherence
      tomography.

PMID- 23881228
TI  - Foreign body response within postoperative perfluoro-N-octane for retinal
      detachment repair: clinical features, grading system, and histopathology.
AB  - PURPOSE: To describe the clinical and histopathologic characteristics of
      inflammatory deposits occurring within intermediate duration postoperative
      perfluoro-n-octane (PFO) for inferior retinal detachment repair. METHODS:
      Prospective interventional case series of consecutive patients with inferior
      retinal detachment treated with intermediate duration postoperative vitreous
      cavity PFO endotamponade were analyzed by ophthalmoscopy for the presence of
      inflammation and white deposits. Ten consecutive samples developing white
      deposits were analyzed microscopically. Clinical variables were analyzed.
      RESULTS: One hundred and eighty-one eyes of 181 patients were included (mean age
      = 52.4 +/- 14 years; mean follow-up = 29.7 +/- 14 months). Fifty of 181 patients
      (28%) developed a characteristic foreign body response with abundant white
      deposits within indwelling PFO. Ten consecutive samples analyzed histologically
      contained abundant macrophages, the absence of additional inflammatory cells, and
      intracytoplasmic optically lucent inclusions. Foreign body response was
      associated with longer duration of PFO (P = 0.003). Perfluoro-n-octane foreign
      body response was not associated with age (P = 0.136), ethnicity (P = 0.101),
      visual outcome (P = 0.157), or persistent intraocular pressure elevation (P =
      0.381). CONCLUSION: A stereotypical foreign body response occurs in ~ 30% of
      patients with postoperative vitreous cavity PFO and becomes clinically apparent
      at 7 days to 10 days after initial placement for rhegmatogenous retinal
      detachment repair. The response consists almost exclusively of macrophages and
      does not seem to be related to either long-term intraocular pressure elevation or
      visual outcome. The response may be related to the duration of indwelling PFO and
      may limit visualization of the retina during PFO removal.

PMID- 23881229
TI  - Treatment of retinal detachment secondary to macular hole in highly myopic eyes:
      pars plana vitrectomy with internal limiting membrane peel and silicone oil
      tamponade.
AB  - PURPOSE: To evaluate efficacy of vitrectomy with internal limiting membrane peel
      and silicone oil tamponade in highly myopic eyes with retinal detachment
      secondary to macular hole (MH). METHODS: Twenty-one consecutive cases of MH
      retinal detachment in highly myopic eyes were retrospectively reviewed. Eyes
      underwent pars plana vitrectomy, internal limiting membrane peeling, and silicone
      oil tamponade. A face-down or side-lying position was maintained postoperatively.
      Silicone oil was removed 3 months to 12 months later. Outcomes included MH
      closure and retinal reattachment rates, best-corrected visual acuity, and
      complication rates. RESULTS: Mean patient age was 59.3 +/- 6.5 years and mean
      spherical equivalent was -15.2 +/- 4.3 diopters. After silicone oil removal, 18
      eyes (86%) had MH closure with retinal reattachment and 2 eyes needed
      reattachment with endolaser photocoagulation and fluid/gas exchange, and 1
      patient refused further treatment. At the last follow-up, median best-corrected
      visual acuity was +1.48 +/- 0.12, up from preoperative +2.11 +/- 0.17 (P = 0.03).
      Transient intraocular pressure elevation was observed in 11 eyes (52%).
      Iatrogenic retinal break occurred in one case. CONCLUSION: Combining pars plana
      vitrectomy with internal limiting membrane peel and silicone oil tamponade was
      safe and effective in treating MH-retinal detachment in highly myopic eyes.
      Silicone oil tamponade may improve initial anatomical success rates because of
      longer tamponade duration.

PMID- 23881230
TI  - Relationship between pregame concentrations of free testosterone and outcome in
      rugby union.
AB  - PURPOSE: To assess the measures of salivary free testosterone and cortisol
      concentrations across selected rugby union matches according to game outcome.
      METHODS: Twenty-two professional male rugby union players were studied across 6
      games (3 wins and 3 losses). Hormone samples were taken 40 min before the game
      and 15 min after. The hormonal data were grouped and compared against competition
      outcomes. These competition outcomes included wins and losses and a game-ranked
      performance score (1-6). RESULTS: Across the entire team, pregame testosterone
      concentrations were significantly higher during winning games than losses (P =
      5.8 * 10-5). Analysis by playing position further revealed that, for the backs,
      pregame testosterone concentrations (P = 3.6 * 10-5) and the testosterone-to
      cortisol ratio T:C (P = .038) were significantly greater before a win than a
      loss. Game-ranked performance score correlated to the team's pregame testosterone
      concentrations (r = .81, P = .049). In backs, pregame testosterone (r = .91, P =
      .011) and T:C (r = .81, P = .05) also correlated to game-ranked performance.
      Analysis of the forwards' hormone concentrations did not distinguish between game
      outcomes, nor did it correlate with game-ranked performance. Game venue (home vs
      away) only affected postgame concentrations of testosterone (P = .018) and
      cortisol (P = 2.58 * 10-4). CONCLUSIONS: Monitoring game-day concentrations of
      salivary free testosterone may help identify competitive readiness in rugby union
      matches. The link between pregame T:C and rugby players in the back position
      suggests that monitoring weekly training loads and enhancing recovery modalities
      between games may also assist with favorable performance and outcome in rugby
      union matches.

PMID- 23881231
TI  - A patterned recombinant human IgM guides neurite outgrowth of CNS neurons.
AB  - Matrix molecules convey biochemical and physical guiding signals to neurons in
      the central nervous system (CNS) and shape the trajectory of neuronal fibers that
      constitute neural networks. We have developed recombinant human IgMs that bind to
      epitopes on neural cells, with the aim of treating neurological diseases. Here we
      test the hypothesis that recombinant human IgMs (rHIgM) can guide neurite
      outgrowth of CNS neurons. Microcontact printing was employed to pattern rHIgM12
      and rHIgM22, antibodies that were bioengineered to have variable regions capable
      of binding to neurons or oligodendrocytes, respectively. rHIgM12 promoted
      neuronal attachment and guided outgrowth of neurites from hippocampal neurons.
      Processes from spinal neurons followed grid patterns of rHIgM12 and formed a
      physical network. Comparison between rHIgM12 and rHIgM22 suggested the
      biochemistry that facilitates anchoring the neuronal surfaces is a prerequisite
      for the function of IgM, and spatial properties cooperate in guiding the assembly
      of neuronal networks. 

PMID- 23881232
TI  - Electroconvulsive therapy improves clinical manifestation with plasma BDNF levels
      unchanged in treatment-resistant depression patients.
AB  - Electroconvulsive therapy (ECT) is the most effective treatment in treatment
      resistant depression; it may modulate intracellular processes in such patients.
      This study aimed to investigate the association between changes in plasma brain
      derived neurotrophic factor (BDNF) levels and the clinical improvements after ECT
      for patients with treatment-resistant depression. Fifty-five inpatients with
      treatment-resistant depression were recruited. The severity of depression was
      measured using the 17-item Hamilton Rating Scale for Depression (HAMD-17) and the
      Clinical Global Impression-Severity (CGI-S) before ECT, after every 3 sessions of
      ECT, and at the end of ECT. Plasma BDNF levels were measured in all subjects
      before and after ECT. The severity of depression was significantly reduced on the
      HAMD-17 (p < 0.001) and the CGI-S (p < 0.001) after the end of ECT. There were no
      significant differences in plasma BDNF levels after ECT (p = 0.615). No
      significant correlation was found between changes in plasma BDNF levels and
      changes in HAMD-17 scores (r = 0.188, p = 0.169). Our results do not support the
      hypothesis that improvements in treatment-resistant depression patients after ECT
      are due to changes in BDNF levels. 

PMID- 23881233
TI  - PEGylation of gold-decorated silica nanoparticles in the aerosol phase.
AB  - Coating of gold-decorated silica nanoparticles with polyethylene glycol (PEG) was
      carried out in the aerosol phase. The process involves first functionalizing the
      nanoparticles at ~225  degrees  C with a bifunctional reactant, 2-mercaptoethanol
      (ME), for which one end is a thiol that attaches to the gold surface and the
      other end is a terminal hydroxyl group, and then introducing ethylene oxide (EO),
      which reacts at ~440  degrees  C with the hydroxyl group via a ring-opening
      polymerization to grow PEG. The morphology, elemental composition and surface
      chemistry of the PEGylated nanoparticles were characterized by means of
      transmission electron microscopy, energy dispersive x-ray spectroscopy in
      scanning transmission electron microscopy, x-ray photoelectron microscopy and
      Fourier transform infrared spectroscopy. The increase in mobility diameter of the
      nanoparticles due to PEG growth was measured on-line by tandem differential
      mobility analysis. The PEG coating thickness was found to increase with increases
      in gold decoration density, flow rate of ME, and flow rate of EO. Coating
      thicknesses up to ~4.5 nm were measured on nanoparticles whose initial mobility
      diameter equaled 39 nm.

PMID- 23881235
TI  - Prevalence and factors associated with neck and jaw muscle modulation of
      tinnitus.
AB  - Forceful contractions of neck and jaw muscles have consistently been shown to
      modulate tinnitus and can be used to screen patients who are responsive to
      somatic stimulation and, therefore, optimal candidates for somatosensory-based
      treatment. To identify the factors associated with somatic modulation of
      tinnitus, 163 patients underwent 19 neck and jaw maneuvers after an extensive
      physiological and audiological profile was compiled. Overall, tinnitus was
      modulated in 57.1% of ears tested. Unilateral tinnitus showed greater prevalence
      of modulation. Neck maneuvers generally decreased tinnitus loudness, whereas jaw
      maneuvers increased loudness. Female gender and buzzing tinnitus were associated
      with a high prevalence of modulation and a decrease in tinnitus loudness. Loud
      tinnitus and low-pitched tonal tinnitus were associated with exacerbation of the
      condition as a result of somatic testing. Use of these characteristics to select
      optimal candidates for somatosensory-based tinnitus therapies may be essential
      for the development of an effective approach for tinnitus treatment. 

PMID- 23881237
TI  - [Participation and support of clinical studies and other scientific
      investigations. Statement of the German Society for Pathology].
AB  - Clinical studies and preclinical investigations are essential in order to test
      new therapies and diagnostics with the aim of sustained improvement in the
      treatment of patients. Fortunately, the number of clinical studies is
      continuously increasing and pathology and tissue-based research are included more
      often. The German Society for Pathology (DGP) and the pathologists it represents
      want to and can support this process and our clinical partners as best as
      possible as an equal partner. With our technologies and our specific expertise we
      can make a substantial contribution to the quality and the success of preclinical
      investigations, clinical studies and implementation of the results into clinical
      pathological diagnostics. In order to support this process the DGP has formulated
      a statement on the participation and support of clinical studies and other
      scientific investigations. 

PMID- 23881236
TI  - [Non-neoplastic alterations of the prostate. Why should pathologists know them?].
AB  - Non-neoplastic changes in the prostatic gland include inflammatory, atrophic,
      hyperplastic and metaplastic reaction patterns of the glandular epithelium and
      the fibromuscular stroma. Furthermore, histoanatomical structures from outside
      the prostatic gland are sometimes included in biopsy material. Knowledge of the
      morphological appearance of benign, reactive lesions is important in order to
      differentiate them from malignancies. To this aim knowing the precise location of
      tissue sampling as well as ancillary immunohistochemical investigations are often
      useful or necessary. 

PMID- 23881238
TI  - [Comments on the statement of the German Society of Pathology (DGP) on clinical
      studies from a clinical perspective].

PMID- 23881239
TI  - Safety and tolerability of tenofovir for preexposure prophylaxis among men who
      have sex with men.

PMID- 23881241
TI  - Microbead-separated thermionic energy converter with enhanced emission current.
AB  - The efficiency of thermionic energy converters is a strong function of the inter
      electrode separation due to space-charge limitations. Here we demonstrate vacuum
      thermionic energy converters constructed using barium dispenser cathodes and thin
      film tungsten anodes, separated by size specific alumina microbeads for simple
      device fabrication and inter-electrode gap control. The current and device
      efficiency at the maximum power point are strongly dependent on the inter
      electrode gap, with a maximum device efficiency of 0.61% observed for a gap on
      the order of 5 MUm. Paths to further reductions in space charge and improved
      anode work function are outlined with potential for over an order of magnitude
      improvement in output power and efficiency. 

PMID- 23881243
TI  - L-Malate dehydrogenase activity in the reductive arm of the incomplete citric
      acid cycle of Nitrosomonas europaea.
AB  - The autotrophic nitrifying bacterium Nitrosomonas europaea does not synthesize 2
      oxoglutarate (alpha-ketoglutarate) dehydrogenase under aerobic conditions and so
      has an incomplete citric acid cycle. L-malate (S-malate) dehydrogenase (MDH) from
      N. europaea was predicted to show similarity to the NADP(+)-dependent enzymes
      from chloroplasts and was separated from the NAD(+)-dependent proteins from most
      other bacteria or mitochondria. MDH activity in a soluble fraction from N.
      europaea ATCC 19718 was measured spectrophotometrically and exhibited simple
      Michaelis-Menten kinetics. In the reductive direction, activity with NADH
      increased from pH 6.0 to 8.5 but activity with NADPH was consistently lower and
      decreased with pH. At pH 7.0, the K m for oxaloacetate was 20 MUM; the K m for
      NADH was 22 MUM but that for NADPH was at least 10 times higher. In the oxidative
      direction, activity with NAD(+) increased with pH but there was very little
      activity with NADP(+). At pH 7.0, the K m for L-malate was 5 mM and the K m for
      NAD(+) was 24 MUM. The reductive activity was quite insensitive to inhibition by
      L-malate but the oxidative activity was very sensitive to oxaloacetate. MDH
      activity was not strongly activated or inhibited by glycolytic or citric acid
      cycle metabolites, adenine nucleotides, NaCl concentrations, or most metal ions,
      but increased with temperature up to about 55  degrees C. The reductive activity
      was consistently 10-20 times higher than the oxidative activity. These results
      indicate that the L-malate dehydrogenase in N. europaea is similar to other
      NAD(+)-dependent MDHs (EC 1.1.1.37) but physiologically adapted for its role in a
      reductive biosynthetic sequence. 

PMID- 23881244
TI  - p53siRNA therapy reduces cell proliferation, migration and induces apoptosis in
      triple negative breast cancer cells.
AB  - p53 protein is probably the best known tumor suppressor. Earlier reports proved
      that human breast cancer cells expressing mutant p53 displayed resistance to
      apoptosis. This study is intended to investigate, the potential applications of
      RNA interference (RNAi) to block p53 expression, as well as its subsequent effect
      on cell growth, apoptosis and migration on a triple negative human breast cancer
      cell line (Hs578T). p53siRNA significantly reduced cell index (CI) compared to
      the control and we observed an inhibition of cellular migration in the interval
      of time between 0 and 30 h, as shown in the data obtained by dynamic evaluation
      using the xCELLigence System. Also, by using PCR-array technology, a panel of 84
      key genes involved in apoptosis was investigated. Our studies indicate that the
      knockdown of p53 expression by siRNA modulates several genes involved in cell
      death pathways and apoptosis, showing statistically significant gene expression
      differences for 22 genes, from which 18 were upregulated and 4 were
      downregulated. The present research also emphasizes the important role of BCL-2
      pro-apoptotic family of genes (Bim, Bak, and Bax) in activating apoptosis and
      reducing cell proliferation by p53siRNA treatment. Death receptors cooperate with
      BCL-2 pro-apoptotic genes in reducing cell proliferation. The limited success may
      be due to the activation of the antiapoptotic gene Mcl-1, and it may be
      associated with the resistance of triple negative breast cancer cells to cancer
      treatment. Thus, targeting p53siRNA pathways using siRNA may serve as a promising
      therapeutic strategy for the treatment of breast cancers.

PMID- 23881245
TI  - Evidence for expression of 11beta-hydroxysteroid dehydrogenase type3
      (HSD11B3/HSD11B1L) in neonatal pig testis.
AB  - 11beta-hydroxysteroid dehydrogenase (HSD11B) catalyzes the interconversion
      between active and inactive glucocorticoid, and is known to exist as two distinct
      isozymes: HSD11B1 and HSD11B2. A third HSD11B isozyme, HSD11B1L (SCDR10b), has
      recently been identified. Human HSD11B1L, which was characterized as a
      unidirectional NADP(+)-dependent cortisol dehydrogenase, appears to be
      specifically expressed in the brain. We previously reported that HSD11B1 and
      abundant HSD11B2 isozymes are expressed in neonatal pig testis and the Km for
      cortisol of NADP(+)-dependent dehydrogenase activity of testicular microsomes
      obviously differs from the same activity catalyzed by HSD11B1 from pig liver
      microsomes. Therefore, we hypothesized that the neonatal pig testis also
      expresses the third type of HSD11B isozyme, and we herein examined further
      evidence regarding the expression of HSD11B1L. (1) The inhibitory effects of
      gossypol and glycyrrhetinic acid on pig testicular microsomal NADP(+)-dependent
      cortisol dehydrogenase activity was clearly different from that of pig liver
      microsomes. (2) A highly conserved human HSD11B1L sequence was observed by RT-PCR
      in a pig testicular cDNA library. (3) mRNA, which contains the amplified
      sequence, was evaluated by real-time PCR and was most strongly expressed in pig
      brain, and at almost the same levels in the kidney as in the testis, but at lower
      levels in the liver. Based on these results, neonatal pig testis appears to
      express glycyrrhetinic acid-resistant HSD11B1L as a third HSD11B isozyme, and it
      may play a physiologically important role in cooperation with the abundantly
      expressed HSD11B2 isozyme in order to prevent Leydig cell apoptosis or GC
      mediated suppression of testosterone production induced by high concentrations of
      activated GC in neonatal pig testis. 

PMID- 23881246
TI  - Tissue-type plasminogen activator mediates neuronal detection and adaptation to
      metabolic stress.
AB  - Adenosine monophosphate-activated protein kinase (AMPK) is an energy sensor that
      regulates cellular adaptation to metabolic stress. Tissue-type plasminogen
      activator (tPA) is a serine proteinase found in the intravascular space, where
      its main role is as thrombolytic enzyme, and in neurons, where its function is
      less well understood. Here, we report that glucose deprivation induces the
      mobilization and package of neuronal tPA into presynaptic vesicles. Mass
      spectrometry and immunohistochemical studies show that the release of this tPA in
      the synaptic space induces AMPK activation in the postsynaptic terminal, and an
      AMPK-mediated increase in neuronal uptake of glucose and neuronal adenosine
      5'(tetrahydrogen triphosphate; ATP) synthesis. This effect is independent of
      tPA's proteolytic properties, and instead requires the presence of functional N
      methyl-D-aspartate receptors (NMDARs). In agreement with these observations,
      positron emission tomography (PET) studies and biochemical analysis with
      synaptoneurosomes indicate that the intravenous administration of recombinant tPA
      (rtPA) after transient middle cerebral artery occlusion (tMCAO) induces AMPK
      activation in the synaptic space and NMDAR-mediated glucose uptake in the
      ischemic brain. These data indicate that the release of neuronal tPA or treatment
      with rtPA activate a cell signaling pathway in the synaptic space that promotes
      the detection and adaptation to metabolic stress. 

PMID- 23881247
TI  - A fast nonlinear regression method for estimating permeability in CT perfusion
      imaging.
AB  - Blood-brain barrier damage, which can be quantified by measuring vascular
      permeability, is a potential predictor for hemorrhagic transformation in acute
      ischemic stroke. Permeability is commonly estimated by applying Patlak analysis
      to computed tomography (CT) perfusion data, but this method lacks precision.
      Applying more elaborate kinetic models by means of nonlinear regression (NLR) may
      improve precision, but is more time consuming and therefore less appropriate in
      an acute stroke setting. We propose a simplified NLR method that may be faster
      and still precise enough for clinical use. The aim of this study is to evaluate
      the reliability of in total 12 variations of Patlak analysis and NLR methods,
      including the simplified NLR method. Confidence intervals for the permeability
      estimates were evaluated using simulated CT attenuation-time curves with
      realistic noise, and clinical data from 20 patients. Although fixating the blood
      volume improved Patlak analysis, the NLR methods yielded significantly more
      reliable estimates, but took up to 12 * longer to calculate. The simplified NLR
      method was ~4 * faster than other NLR methods, while maintaining the same
      confidence intervals (CIs). In conclusion, the simplified NLR method is a new,
      reliable way to estimate permeability in stroke, fast enough for clinical
      application in an acute stroke setting. 

PMID- 23881248
TI  - TAT-Hsp70 induces neuroprotection against stroke via anti-inflammatory actions
      providing appropriate cellular microenvironment for transplantation of neural
      precursor cells.
AB  - Heat-shock protein 70 (Hsp70) protects against cerebral ischemia, which is
      attributed to its chaperone activity. However, recent reports also describe pro
      inflammatory actions of Hsp70 via activation of Toll-like receptors (TLR). Using
      membrane-permeable transactivator of transcription (TAT)-Hsp70, we analyzed TAT
      Hsp70-induced neuroprotection and its underlying mechanism after cerebral
      ischemia in mice. Infusion of TAT-Hsp70 reduced infarct volume and enhanced blood
      brain barrier integrity on day 3 poststroke, when given no later than 12 hours.
      The latter was associated with reduction of microglial activation, although
      upregulation of pro-inflammatory TLR-2/4 was observed both in verum and in
      control animals. Nevertheless, protein abundance and nuclear translocation of
      downstream nuclear factor kappa B (NF-kappaB) as well as proteasomal degradation
      of the NF-kappaB regulator Ikappa B alpha (IkappaB-alpha) were significantly
      reduced by TAT-Hsp70. TAT-Hsp70-induced neuroprotection and functional recovery
      were restricted to 4 weeks only. However, TAT-Hsp70 provided an appropriate
      extracellular milieu for delayed intravenous transplantation of adult neural
      precursor cells (NPCs). Thus, NPCs that were grafted 28 days poststroke induced
      long-term neuroprotection for at least 3 months, which was not due to integration
      of grafted cells but rather due to paracrine effects of transplanted NPCs.
      Conclusively, TAT-Hsp70 ameliorates postischemic inflammation via proteasome
      inhibition, thus providing an appropriate extracellular milieu for delayed NPC
      transplantation and culminating in long-term neuroprotection. 

PMID- 23881250
TI  - Vertebra identification using template matching modelmp and K-means clustering.
AB  - PURPOSE: Accurate vertebra detection and segmentation are essential steps for
      automating the diagnosis of spinal disorders. This study is dedicated to vertebra
      alignment measurement, the first step in a computer-aided diagnosis tool for
      cervical spine trauma. Automated vertebral segment alignment determination is a
      challenging task due to low contrast imaging and noise. A software tool for
      segmenting vertebrae and detecting subluxations has clinical significance. A
      robust method was developed and tested for cervical vertebra identification and
      segmentation that extracts parameters used for vertebra alignment measurement.
      METHODS: Our contribution involves a novel combination of a template matching
      method and an unsupervised clustering algorithm. In this method, we build a
      geometric vertebra mean model. To achieve vertebra detection, manual selection of
      the region of interest is performed initially on the input image. Subsequent
      preprocessing is done to enhance image contrast and detect edges. Candidate
      vertebra localization is then carried out by using a modified generalized Hough
      transform (GHT). Next, an adapted cost function is used to compute local voted
      centers and filter boundary data. Thereafter, a K-means clustering algorithm is
      applied to obtain clusters distribution corresponding to the targeted vertebrae.
      These clusters are combined with the vote parameters to detect vertebra centers.
      Rigid segmentation is then carried out by using GHT parameters. Finally, cervical
      spine curves are extracted to measure vertebra alignment. RESULTS: The proposed
      approach was successfully applied to a set of 66 high-resolution X-ray images.
      Robust detection was achieved in 97.5 % of the 330 tested cervical vertebrae.
      CONCLUSIONS: An automated vertebral identification method was developed and
      demonstrated to be robust to noise and occlusion. This work presents a first step
      toward an automated computer-aided diagnosis system for cervical spine trauma
      detection.

PMID- 23881249
TI  - Dabigatran for periprocedural anticoagulation following radiofrequency ablation
      for atrial fibrillation: a meta-analysis of observational studies.
AB  - PURPOSE: Dabigatran is approved for prevention of stroke or systemic embolism in
      patients with nonvalvular atrial fibrillation (AF). The safety and effectiveness
      of periprocedural dabigatran in ablation for AF are unknown. METHODS: We
      performed a meta-analysis of all studies comparing periprocedural dabigatran with
      warfarin for anticoagulation in AF ablation. Studies of >100 patients with post
      procedure follow-up were included. Outcomes were compared by calculating maximum
      likelihood estimates with confidence intervals. The co-primary endpoints were
      neurological events and major bleeding. RESULTS: Ten cohort studies were
      included, including a total of 1,501 patients receiving dabigatran and 2,356
      receiving warfarin. The mean age was 59-64 years and inclusion of women varied
      (10-33 %). Intra-procedural unfractionated heparin and irrigated ablation
      catheters were used routinely. Adverse events were low overall; however, the
      dabigatran group demonstrated a numerical excess of neurological events (10/1,501
      [0.7 %] versus 4/2,356 [0.2 %]), but equivalent major bleeding outcomes (24/1,501
      [1.6 %] versus 40/2,356 [1.7 %]). In the meta-analysis, there was a
      nonsignificant trend towards higher rates of the composite primary endpoints (any
      neurological event or major bleeding) in the dabigatran group. Dabigatran
      demonstrated a significantly higher rate of neurological events (estimated
      absolute risk difference 0.0047, 95 % confidence interval 0.0007 to 0.0099).
      CONCLUSIONS: Compared with warfarin, dabigatran may be associated with a higher
      frequency of periprocedural neurological events following radiofrequency ablation
      of AF. Randomized clinical trials are needed to definitively assess the safety
      and efficacy of novel oral anticoagulant use for periprocedural anticoagulation
      for ablation of AF.

PMID- 23881251
TI  - Interventional radiology virtual simulator for liver biopsy.
AB  - PURPOSE: Training in Interventional Radiology currently uses the apprenticeship
      model, where clinical and technical skills of invasive procedures are learnt
      during practice in patients. This apprenticeship training method is increasingly
      limited by regulatory restrictions on working hours, concerns over patient risk
      through trainees' inexperience and the variable exposure to case mix and
      emergencies during training. To address this, we have developed a computer-based
      simulation of visceral needle puncture procedures. METHODS: A real-time framework
      has been built that includes: segmentation, physically based modelling, haptics
      rendering, pseudo-ultrasound generation and the concept of a physical mannequin.
      It is the result of a close collaboration between different universities,
      involving computer scientists, clinicians, clinical engineers and occupational
      psychologists. RESULTS: The technical implementation of the framework is a robust
      and real-time simulation environment combining a physical platform and an
      immersive computerized virtual environment. The face, content and construct
      validation have been previously assessed, showing the reliability and
      effectiveness of this framework, as well as its potential for teaching visceral
      needle puncture. CONCLUSION: A simulator for ultrasound-guided liver biopsy has
      been developed. It includes functionalities and metrics extracted from cognitive
      task analysis. This framework can be useful during training, particularly given
      the known difficulties in gaining significant practice of core skills in
      patients.

PMID- 23881253
TI  - Real-time image processing for label-free enrichment of Actinobacteria cultivated
      in picolitre droplets.
AB  - The majority of today's antimicrobial therapeutics is derived from secondary
      metabolites produced by Actinobacteria. While it is generally assumed that less
      than 1% of Actinobacteria species from soil habitats have been cultivated so far,
      classic screening approaches fail to supply new substances, often due to limited
      throughput and frequent rediscovery of already known strains. To overcome these
      restrictions, we implement high-throughput cultivation of soil-derived
      Actinobacteria in microfluidic pL-droplets by generating more than 600,000 pure
      cultures per hour from a spore suspension that can subsequently be incubated for
      days to weeks. Moreover, we introduce triggered imaging with real-time image
      based droplet classification as a novel universal method for pL-droplet sorting.
      Growth-dependent droplet sorting at frequencies above 100 Hz is performed for
      label-free enrichment and extraction of microcultures. The combination of both
      cultivation of Actinobacteria in pL-droplets and real-time detection of growing
      Actinobacteria has great potential in screening for yet unknown species as well
      as their undiscovered natural products.

PMID- 23881254
TI  - Intelligent supramolecular assembly of aromatic block molecules in aqueous
      solution.
AB  - The construction of supramolecular nanoscopic architectures has been intensively
      pursued because of their unique features for applications in nanoscience and
      biomimetic chemistry. Molecular self-assemblies of aromatic rod-coil amphiphiles
      consisting of rigid rod segments and hydrophilic flexible chains in aqueous
      solution provide a facile avenue into this area. This feature article highlights
      the recent progress regarding the construction of aqueous assemblies that result
      from the sophisticated design of aromatic rod-coils, with the aim to develop
      stimuli-responsive systems and bioactive materials. Important factors affecting
      the self-assembly morphologies are discussed and summarized. Dynamic structural
      changes triggered by temperature and guest molecules are demonstrated. Finally,
      the perspective of bioactive nanostructures originated from self-assembly of
      aromatic block amphiphiles is also introduced. 

PMID- 23881252
TI  - Short toxin-like proteins attack the defense line of innate immunity.
AB  - ClanTox (classifier of animal toxins) was developed for identifying toxin-like
      candidates from complete proteomes. Searching mammalian proteomes for short toxin
      like proteins (coined TOLIPs) revealed a number of overlooked secreted short
      proteins with an abundance of cysteines throughout their sequences. We applied
      bioinformatics and data-mining methods to infer the function of several top
      predicted candidates. We focused on cysteine-rich peptides that adopt the fold of
      the three-finger proteins (TFPs). We identified a cluster of duplicated genes
      that share a structural similarity with elapid neurotoxins, such as alpha
      bungarotoxin. In the murine proteome, there are about 60 such proteins that
      belong to the Ly6/uPAR family. These proteins are secreted or anchored to the
      cell membrane. Ly6/uPAR proteins are associated with a rich repertoire of
      functions, including binding to receptors and adhesion. Ly6/uPAR proteins
      modulate cell signaling in the context of brain functions and cells of the innate
      immune system. We postulate that TOLIPs, as modulators of cell signaling, may be
      associated with pathologies and cellular imbalance. We show that proteins of the
      Ly6/uPAR family are associated with cancer diagnosis and malfunction of the
      immune system. 

PMID- 23881255
TI  - Intra-articular clonidine for post-operative analgesia following arthroscopic
      knee surgery: a systematic review and meta-analysis.
AB  - PURPOSE: To assess the efficacy and safety of a single dose of intra-articular
      clonidine for post-operative pain following arthroscopic knee surgery by
      analyzing relevant randomized controlled trials (RCTs). METHODS: PubMed, EMBASE,
      Cochrane Library, ISI Web of knowledge, Chinese Biomedical Literature Database,
      Google Scholar and other databases were searched for RCTs comparing a single dose
      of intra-articular clonidine with placebo for post-operative pain following
      arthroscopic knee surgery. Risk of bias of included studies was assessed by
      Cochrane Collaboration's tool, and data were analyzed by RevMan 5.1 software.
      Pain intensity, supplementary analgesic use and side effects were evaluated as
      the outcomes. RESULTS: Seven RCTs were included, and the results of the meta
      analysis showed that intra-articular clonidine reduced the pain intensity for the
      first 4 h after surgery, reduced the risk of using rescue analgesics and the
      incidence of post-operative nausea, but increased the risk of hypotension after
      surgery. CONCLUSIONS: A single dose of intra-articular clonidine has a definite
      analgesic effect, but the analgesic effect is mild and short lasting, which is
      just for 4 h after injection, and intra-articular clonidine alone could not
      provide sufficient post-operative analgesia following arthroscopic knee surgery.
      Post-operative hypotension may be the side effect that should be paid the most
      attention in the ambulatory setting. LEVEL OF EVIDENCE: II.

PMID- 23881256
TI  - Preoperative asymmetry in load distribution during quiet stance persists
      following total knee arthroplasty.
AB  - PURPOSE: Preoperative function has been shown to persist posttotal knee
      arthroplasty. However, it remains unclear whether asymmetries are task specific.
      Therefore, we investigated postoperative asymmetries in loading during quiet
      stance and walking gait. METHODS: Ten patients with end-stage knee osteoarthritis
      scheduled for total knee arthroplasty were studied at baseline (preoperative), 6
      week, 3- and 6-month postoperative. Load distribution and balance were quantified
      during quiet stance. Furthermore, dynamic loading was quantified during walking
      gait. Patient satisfaction was assessed using the Knee Osteoarthritis and injury
      Outcome Score. RESULTS: Preoperatively, load distribution was significantly
      different between limbs, with approximately 70% of the load through the
      contralateral or 'good' side. Asymmetries persisted and up to 6-month
      postoperative during quiet stance. No significant change was found in balance.
      During walking, preoperative loading asymmetry was present; however, no
      significant postoperative loading asymmetries were identified. CONCLUSIONS: Total
      knee arthroplasty does not appear to significantly change load distribution or
      balance 6-month postoperative during quiet stance; however, during walking gait,
      symmetry appears to be restored. This could be potentially improved through
      enhanced rehabilitation. LEVEL OF EVIDENCE: Therapeutic study, Level IV.

PMID- 23881257
TI  - Joint line reconstruction in medial unicompartmental knee arthroplasty:
      development and validation of a measurement method.
AB  - PURPOSE: Preservation of the joint line in total knee arthroplasty (TKA) has
      shown to be an important factor for the long-term outcome, especially in revision
      TKA. For unicompartmental knee arthroplasty (UKA), the role of the joint line has
      neither been investigated nor is it consciously respected during implantation.
      Thus, the aim was to establish and validate a standardised measurement method to
      determine the joint line in UKA. METHODS: As there is no established method to
      evaluate changes in the joint line radiologically, we introduced two methods and
      correlated them. The methods were first validated in a cadaver model by a
      controlled rotational study. Then, the joint line of 29 patients with an UKA
      (Oxford, Biomet, Bridgend, UK) was determined on pre- and post-operative
      radiographs. Both methods were tested by intra- and inter-rater reliability.
      RESULTS: Both methods showed a good intra- and inter-rater reliability.
      Furthermore, there was only little bias in agreement between both methods and
      raters. Measurements of the 29 UKA patients revealed that the joint line was more
      distally by a mean of 4.4 +/- 1.2 mm after surgery. CONCLUSIONS: The study
      provides for the first time a reliable and standardised measurement tool to
      determine the changes in the joint line after implantation of an UKA. The
      instrument should be used in further studies to evaluate the impact of the joint
      line on the long-term outcome, the load in the two non-replaced knee compartments
      and on the ligaments.

PMID- 23881258
TI  - Tepidibacillus fermentans gen. nov., sp. nov.: a moderately thermophilic
      anaerobic and microaerophilic bacterium from an underground gas storage.
AB  - A novel moderately thermophilic bacterium, strain STGH(T), was isolated from
      Severo-Stavropolskoye underground gas storage (Russia). Cells of strain STGH(T)
      were spore-forming motile straight rods 0.3 MUm in diameter and 2.0-4.0 MUm in
      length having a Gram-positive cell wall structure. The temperature range for
      growth was 36-65  degrees C, with an optimum at 50-52  degrees C. The pH range
      for growth was 5.5-8.0, with an optimum at pH 7.0-7.5. Growth of strain STGH(T)
      was observed at NaCl concentrations ranging from 0 to 4.0 % (w/v) with an optimum
      at 1.0 % (w/v). Strain STGH(T) grew anaerobically by reduction of nitrate,
      thiosulfate, S(0) and AQDS using a number of complex proteinaceous compounds,
      organic acids and carbohydrates as electron donors. Nitrate was reduced to
      nitrite; thiosulfate and sulfur were reduced to sulfide. It also was able to
      ferment pyruvate, glucose, fructose, and maltose. The strain STGH(T) did not grow
      under aerobic conditions during incubation with atmospheric concentration of
      oxygen but was able to microaerobic growth (up to 10 % of oxygen in gas phase).
      The G+C content of DNA of strain STGH(T) was 34.8 mol%. 16S rRNA gene sequence
      analysis revealed that the isolated organism belongs to the class Bacilli. We
      propose to assign strain STGH(T) to a new species of a novel genus Tepidibacillus
      fermentans gen. nov., sp.nov. The type strain is STGH(T) (=DSM 23802(T), =VKM B
      2671(T)).

PMID- 23881259
TI  - New sulfate-reducing bacteria isolated from Buryatian alkaline brackish lakes:
      description of Desulfonatronum buryatense sp. nov.
AB  - New strains of sulfate-reducing bacteria were isolated from two alkaline brackish
      lakes located in the Siberian region of Russia, namely in the Southern
      Transbaikalia, Buriatia. The article presents data describing morphology,
      physiology, and biochemical characteristics of the isolated strains. These
      strains Ki4, Ki5, and Su2 were mesophilic and alkaliphilic with optimal growth at
      pH 8.9, 9.4, and 10.0, respectively. All isolated strains utilized lactate,
      formate, and ethanol in the presence of sulfate for growth and sulfidogenesis
      accompanied with formation of acetate and CO2. Strains Ki5 and Su2 were able to
      reduce Fe(III). The DNA G + C content in strains Ki4, Ki5 and Su2 was 56.3, 48.8
      and 59.6 mol%, respectively. According to phylogenetic analysis of 16S rRNA
      sequences, the new strains were clustered within the genus Desulfonatronum, and
      the closest relative D. lacustre Z-7951(T) (=DSM 10312(T)) showed 99.3-99.6 %
      similarity. DNA-DNA relatedness values of the strains Ki4, Ki5, and Su2 with D.
      lacustre Z-7951(T) were 89, 53, and 79 %, respectively. Polyphasic taxonomy data
      suggest that strain Ki5(T) is representative of the proposed novel species
      Desulfonatronum buryatense sp. nov.

PMID- 23881261
TI  - Retraction note to: Glioma grading: sensitivity, specificity, positive and
      negative predictive values of diffusion and perfusion imaging.

PMID- 23881260
TI  - Growth arrest-specific protein 6 attenuates neutrophil migration and acute lung
      injury in sepsis.
AB  - Sepsis is an acute inflammatory condition that can result in multiple organ
      failure and acute lung injury. Growth arrest-specific protein 6 (Gas6) is a broad
      regulator of the innate immune response involved with the nuclear factor kappaB
      signaling pathway. We hypothesized that Gas6 could have a protective role in
      attenuating the severity of acute lung injury and sepsis. Male mice were
      subjected to sepsis by cecal ligation and puncture (CLP) after which recombinant
      murine Gas6 (rmGas6; 5 MUg/mouse) or normal saline (vehicle) was administered
      intravenously. Blood and lung tissues were collected at 20 h after CLP for
      various measurements. Treatment with rmGas6 significantly reduced serum levels of
      the injury markers aspartate aminotransferase, alanine aminotransferase, and
      lactate dehydrogenase, as well as proinflammatory cytokines interleukin 6 (IL-6)
      and IL-17, compared with the vehicle group (P < 0.05). The parenchyma of the
      lungs damaged by CLP was attenuated by rmGas6 treatment. Lung mRNA levels of
      tumor necrosis factor alpha, IL-1beta, IL-6, IL-17, and macrophage inflammatory
      protein 2 (MIP-2) were decreased by 60%, 86%, 82%, 93%, and 82%, respectively,
      with rmGas6 treatment as determined by real-time reverse transcriptase-polymerase
      chain reaction (P < 0.05). The degradation of IkappaB-alpha induced by CLP in the
      lungs was inhibited by rmGas6 treatment. The number of neutrophils and
      myeloperoxidase activity in the lungs were significantly reduced in the rmGas6
      group. Moreover, rmGas6 reduced the in vitro migration of differentiated human
      promyelocytic HL60 cells by 64%. Finally, the 10-day survival rate of mice
      subjected to CLP was increased from 31% in the vehicle group to 67% in the rmGas6
      group (P < 0.05). Thus, Gas6 has potential to be developed as a novel therapeutic
      agent to treat patients with sepsis and acute lung injury. 

PMID- 23881262
TI  - Spatio-temporal analysis of type 2 diabetes mellitus based on differential
      expression networks.
AB  - T2DM is complex in its dynamical dependence on multiple tissues, disease states,
      and factors' interactions. However, most existing work devoted to characterizing
      its pathophysiology from one static tissue, individual factors, or single state.
      Here we perform a spatio-temporal analysis on T2DM by developing a new form of
      molecular network, i.e. 'differential expression network' (DEN), which can
      reflect phenotype differences at network level. Static DENs show that three
      tissues (white adipose, skeletal muscle, and liver) all suffer from severe
      inflammation and perturbed metabolism, among which metabolic functions are
      seriously affected in liver. Dynamical analysis on DENs reveals metabolic
      function changes in adipose and liver are consistent with insulin resistance (IR)
      deterioration. Close investigation on IR pathway identifies 'disease
      interactions', revealing that IR deterioration is earlier than that on SlC2A4 in
      adipose and muscle. Our analysis also provides evidence that rising of insulin
      secretion is the root cause of IR in diabetes. 

PMID- 23881264
TI  - A comparison of impact of fatigue on cognitive, physical, and psychosocial status
      in patients with fibromyalgia and rheumatoid arthritis.
AB  - This study was performed to compare the impact of fatigue on different aspects of
      quality of life in patients with rheumatoid arthritis (RA) and fibromyalgia
      syndrome (FM). This study involved subjects with FM (n = 45) and RA (n = 44).
      Impact of fatigue on physical, cognitive, and psychosocial status was measured
      with Fatigue Impact Scale (FIS) and health-related quality of life (HRQoL) with
      the Medical Outcome Study Short Form 36 (SF-36). Multiple regression analyses
      were used to evaluate impact of fatigue on quality of life by taking into account
      clinical symptoms and disease activity scores in these two patient groups.
      Although the severity of fatigue assessed by FSS was the same in FM and RA;
      according to Fatigue Impact Scale, fatigue has higher impact on cognitive
      function in FM (mean +/- SD; 28.8 +/- 19.9), and on the other hand, it has higher
      impact on mainly physical component (mean +/- SD; 26.3 +/- 4.9) in RA. Regarding
      all the clinical symptoms and disease activity scores, multiple regression models
      showed that fatigue together with pain affected the HRQoL (SF-36) in both patient
      groups. Fatigue has different impacts on QoL in FM and RA, respectively. Together
      with pain, fatigue lead FM patients to see disease as having worse health in
      terms of mental function, whereas it leads to poor health in terms of physical
      function in RA.

PMID- 23881265
TI  - Systemic involvements and preferred treatments in a large cohort of Behcet's
      disease.
AB  - The immunosuppressive drugs are widely used in systemic involvements of Behcet's
      disease. This study is aimed to investigate the extent of clinical involvement
      and preferred treatment approaches for type of involvements in Behcet's patients
      from the whole country. All patients with the diagnosis of Behcet's disease were
      enrolled to the study. These patients analyzed whether they fulfill the
      International Study Group Criteria, and only those were further evaluated.
      Demographic and clinical characteristics, laboratory results and treatments ever
      used were recorded. Further analysis is done regarding clinical manifestations
      and preferred therapeutic approaches. A total of 863 patients with the diagnosis
      of Behcet's disease were detected, but 682 of them (female/male: 113/569) found
      to be appropriate for analysis. The remaining patients were included to the
      analysis. The frequencies of articular, ophthalmic and vascular involvement were
      49, 43 and 21 %, respectively. Colchicine and corticosteroids were the most
      preferred agents. The immunosuppressive agents frequently used for organ
      involvements were azathioprine, cyclosporine A, interferon-alpha, sulphasalazine
      and cyclophosphamide with decreasing order of frequency. In this relatively young
      population composed from all over the country, the frequency of ophthalmologic,
      venous and neurological involvement is less frequent than previous reported
      cohorts. Azathioprine and cyclosporine were the drugs of choice as a chronic
      immunosuppressive agent in patients with organ involvement. The previously
      reported increased frequencies in other cohorts could be a result of the
      reference of severe patients to dedicated centers.

PMID- 23881266
TI  - Sphingosine kinase 2: a controversial role in arthritis.
AB  - SphK2 is a nuclear protein that suppresses cell proliferation by inhibiting DNA
      synthesis, while also enhancing apoptosis in diverse cell types. ABC294640 (a
      selectively SphK2 inhibitor) attenuated the knee joint histological damage and
      pain associated with MIA-induced OA in rats. However, recent studies revealed
      that genetic inhibition of SphK2 did not significantly impact the severity or
      progression of inflammatory arthritis, while pharmacologic inhibition of SphK2
      led to significantly more severe arthritis. Therefore, SphK2 plays a
      controversial role in arthritis. 

PMID- 23881267
TI  - Relative efficacy and safety of preservative-free latanoprost (T2345) for the
      treatment of open-angle glaucoma and ocular hypertension: an adjusted Indirect
      comparison meta-analysis of randomized clinical trials.
AB  - AIM: To assess the relative efficacy and tolerability of preservative-free
      latanoprost (T2345) compared with other prostaglandin analogues (PGA) for the
      treatment of open-angle glaucoma and ocular hypertension by adjusted indirect
      comparison meta-analysis. METHODS: Randomized, controlled trials evaluating PGA
      for the treatment of open-angle glaucoma and ocular hypertension were identified
      by a systematic literature review in MEDLINE, EMBASE, and Cochrane Controlled
      Trials Register (up to December 2011) databases. The effect size for each
      treatment and heterogeneity were assessed by classical pairwise meta-analysis
      (direct comparisons). Adjusted indirect comparisons were performed by using
      Bucher method. The main endpoints were intraocular pressure (IOP) measured at 3
      months and incidence of hyperemia. RESULTS: Twenty-one studies were included in
      the meta-analysis. No statistically significant differences in IOP at 3 months
      were seen between T2345 and travoprost [preserved with benzalkonium chloride
      (BAK), polyquaternium-1 or sofzia], and other BAK-preserved PGA: bimatoprost
      0.03%, bimatoprost 0.01%, or latanoprost. T2345 was statistically significantly
      superior to BAK-tafluprost (mean difference: 0.47 mm Hg, 95% confidence interval,
      [-1.52;-0.28]). The risk of hyperemia was statistically significantly lower with
      T2345 than with all the other PGA. CONCLUSIONS: Indirect comparisons never found
      preservative-free latanoprost (T2345) to be statistically significantly inferior
      to the other PGA in terms of efficacy on IOP and showed statistically significant
      superiority over BAK-tafluprost. The risk of hyperemia was statistically
      significantly lower with T2345 than with all the other PGA.

PMID- 23881269
TI  - High-yield synthesis of silicon carbide nanowires by solar and lamp ablation.
AB  - We report a reasonably high yield (~50%) synthesis of silicon carbide (SiC)
      nanowires from silicon oxides and carbon in vacuum, by novel solar and lamp
      photothermal ablation methods that obviate the need for catalysis, and allow
      relatively short reaction times (~10 min) in a nominally one-step process that
      does not involve toxic reagents. The one-dimensional core/shell beta-SiC/SiOx
      nanostructures-characterized by SEM, TEM, HRTEM, SAED, XRD and EDS-are typically
      several microns long, with core and outer diameters of about 10 and 30 nm,
      respectively. HRTEM revealed additional distinctive nanoscale structures that
      also shed light on the formation pathways.

PMID- 23881270
TI  - Reliability of physiological attributes and their association with stochastic
      cycling performance.
AB  - PURPOSE: To assess the reliability of a 5-min-stage graded exercise test (GXT)
      and determine the association between physiological attributes and performance
      over stochastic cycling trials of varying distance. METHODS: Twenty-eight well
      trained male cyclists performed 2 GXTs and either a 30-km (n = 17) or a 100-km
      stochastic cycling time trial (n = 9). Stochastic cycling trials included periods
      of high-intensity efforts for durations of 250 m, 1 km, or 4 km depending on the
      test being performing. RESULTS: Maximal physiological attributes were found to be
      extremely reliable (maximal oxygen uptake [VO2max]: coefficient of variation [CV]
      3.0%, intraclass correlation coefficient [ICC] .911; peak power output [PPO]: CV
      3.0%, ICC .913), but a greater variability was found in ventilatory thresholds
      and economy. All physiological variables measured during the GXT, except economy
      at 200 W, were correlated with 30-km cycling performance. Power output during the
      250-m and 1-km efforts of the 30-km trial were correlated with VO2max, PPO, and
      the power output at the second ventilatory threshold (r = .58-.82). PPO was the
      only physiological attributed measured during the GXT to be correlated with
      performance during the 100-km cycling trial (r = .64). CONCLUSIONS: Many
      physiological variables from a reliable GXT were associated with performance over
      shorter (30-km) but not longer (100-km) stochastic cycling trials.

PMID- 23881271
TI  - Impulsiveness in patients with bulimia nervosa: electrophysiological evidence of
      reduced inhibitory control.
AB  - OBJECTIVES: Bulimia nervosa (BN) is associated with a deficit of self-regulatory
      control and impulsivity. The present study aimed to clarify whether an impaired
      inhibitory control due to hyperarousal underlies impulsivity in BN subjects.
      METHODS: Event-related potentials (ERPs) were recorded in 17 female patients with
      BN and 17 healthy controls during a three-tone oddball task. ERP components
      related to inhibition of irrelevant distractor stimuli, as well as effortful
      processing, were analyzed. Standardized low-resolution electromagnetic tomography
      (sLORETA) was used to assess ERP source activity. RESULTS: Compared to healthy
      controls, BN patients showed reduced amplitude and shorter latency of the N200
      (N2), increased amplitude and shorter latency of the target slow wave (SW), and
      higher amplitude of the P300 for distractor stimuli (P3a) and for targets (P3b).
      sLORETA showed the following: (1) higher activity of the P3a generators in the
      left parietal cortex, bilateral precuneus and right frontal and anterior
      cingulate for distractor stimuli and (2) lower activity of the SW generators in
      the left medial frontal gyrus, bilateral superior frontal, anterior cingulate and
      cuneus for target stimuli. The reduction of the N2 latency was associated with
      the Barratt scores for impulsiveness. CONCLUSIONS: The observed
      electrophysiological abnormalities suggest a condition of hyperarousal, with
      impaired suppression of irrelevant stimuli due to abnormal cortical activation
      and reduced signal-to-noise ratio. Our findings point to functional abnormalities
      within a neural system that subserves attention and self-regulatory control,
      which may contribute to impulsive behaviors in BN.

PMID- 23881272
TI  - Exploring public attitudes towards approaches to discussing costs in the clinical
      encounter.
AB  - BACKGROUND: Patients' willingness to discuss costs of treatment alternatives with
      their physicians is uncertain. OBJECTIVE: To explore public attitudes toward
      doctor-patient discussions of insurer and out-of-pocket costs and to examine
      whether several possible communication strategies might enhance patient
      receptivity to discussing costs with their physicians. DESIGN: Focus group
      discussions and pre-discussion and post-discussion questionnaires. PARTICIPANTS:
      Two hundred and eleven insured individuals with mean age of 48 years, 51 %
      female, 34 % African American, 27 % Latino, and 50 % with incomes below 300 % of
      the federal poverty threshold, participated in 22 focus groups in Santa Monica,
      CA and in the Washington, DC metro area. MAIN MEASUREMENTS: Attitudes toward
      discussing out-of-pocket and insurer costs with physicians, and towards
      physicians' role in controlling costs; receptivity toward recommended
      communication strategies regarding costs. KEY RESULTS: Participants expressed
      more willingness to talk to doctors about personal costs than insurer costs.
      Older participants and sicker participants were more willing to talk to the
      doctor about all costs than younger and healthier participants (OR = 1.8, p =
      0.004; OR = 1.6, p = 0.027 respectively). Participants who face cost-related
      barriers to accessing health care were in greater agreement than others that
      doctors should play a role in reducing out-of-pocket costs (OR = 2.4, p = 0.011).
      Participants did not endorse recommended communication strategies for discussing
      costs in the clinical encounter. In contrast, participants stated that trust in
      one's physician would enhance their willingness to discuss costs. Perceived
      impediments to discussing costs included rushed, impersonal visits, and
      clinicians who are insufficiently informed about costs. CONCLUSIONS: This study
      suggests that trusting relationships may be more conducive than any particular
      discussion strategy to facilitating doctor-patient discussions of health care
      costs. Better public understanding of how medical decisions affect insurer costs
      and how such costs ultimately affect patients personally will be necessary if
      discussions about insurer costs are to occur in the clinical encounter.

PMID- 23881274
TI  - Differentiation and distribution of cordyline viruses 1-4 in Hawaiian ti plants
      (Cordyline fruticosa L.).
AB  - Common green ti plants (Cordyline fruticosa L.) in Hawaii can be infected by four
      recently characterized closteroviruses that are tentative members of the proposed
      genus Velarivirus. In this study, a reverse-transcription polymerase chain
      reaction (RT-PCR) assay developed to detect and distinguish Cordyline virus 1
      (CoV-1), CoV-2, CoV-3, and CoV-4 was used to determine: (i) the distribution of
      these viruses in Hawaii; and (ii) if they are involved in the etiology of ti
      ringspot disease. One hundred and thirty-seven common green ti plants with and
      without ti ringspot symptoms were sampled from 43 sites on five of the Hawaiian
      Islands and underwent the RT-PCR assay. Eleven ornamental ti varieties were also
      sampled and assayed. Based on this survey, it appears none of the CoVs are
      involved in the etiology of ti ringspot. The observation of a non-uniform
      geographic distribution of the CoVs in common green ti, combined with the
      presence of CoVs in seed-derived ornamental varieties, suggests active vector
      transmission. Eight herbarium specimens collected between 1903 and 2003 from
      plants on the island of Oahu also underwent the RT-PCR assay. Amplifiable RNA was
      isolated from accessions collected in 1985 or later, however only the 2003
      accession was found to harbor CoVs. 

PMID- 23881273
TI  - Safety and efficacy of modified FOLFOX6 plus high-dose bevacizumab in second-line
      or later treatment of patients with metastatic colorectal cancer.
AB  - AIM: The aim of this retrospective study was to show the efficacy and safety of
      modified FOLFOX6 plus high-dose bevacizumab (10 mg/kg/2 weeks) in the second-line
      or later treatment of metastatic colorectal cancer. METHODS: A total of 24
      consecutive patients treated between August 2007 and August 2009 were included in
      this retrospective study. None of the patients had received bevacizumab as part
      of prior treatment. RESULTS: All 24 patients received modified FOLFOX6 plus high
      dose bevacizumab and were followed for a median of 36.9 months. Overall response
      rate was 29%. Median progression-free survival was 7.5 months, and median overall
      survival was 17.3 months. Grade 3/4 adverse events were: neutropenia (54.2%),
      leukopenia (25.0%), neuropathy (12.5%), hypertension (12.5%), thrombocytopenia
      (8.3%), and decreased haemoglobin, gastrointestinal haemorrhage, wound
      complications, nausea, diarrhoea, mucositis and fatigue (each 4.2%). CONCLUSION:
      Modified FOLFOX6 plus high-dose bevacizumab may be useful in the second-line
      treatment of patients with metastatic colorectal cancer who have not received
      bevacizumab.

PMID- 23881275
TI  - Identification of genes critical for resistance to infection by West Nile virus
      using RNA-Seq analysis.
AB  - The West Nile virus (WNV) is an emerging infection of biodefense concern and
      there are no available treatments or vaccines. Here we used a high-throughput
      method based on a novel gene expression analysis, RNA-Seq, to give a global
      picture of differential gene expression by primary human macrophages of 10
      healthy donors infected in vitro with WNV. From a total of 28 million reads per
      sample, we identified 1,514 transcripts that were differentially expressed after
      infection. Both predicted and novel gene changes were detected, as were gene
      isoforms, and while many of the genes were expressed by all donors, some were
      unique. Knock-down of genes not previously known to be associated with WNV
      resistance identified their critical role in control of viral infection. Our
      study distinguishes both common gene pathways as well as novel cellular
      responses. Such analyses will be valuable for translational studies of
      susceptible and resistant individuals--and for targeting therapeutics--in
      multiple biological settings.

PMID- 23881276
TI  - Small ruminant lentiviruses (SRLVs) break the species barrier to acquire new host
      range.
AB  - Zoonotic events of simian immunodeficiency virus (SIV) from non-human primates to
      humans have generated the acquired immunodeficiency syndrome (AIDS), one of the
      most devastating infectious disease of the last century with more than 30 million
      people dead and about 40.3 million people currently infected worldwide. Human
      immunodeficiency virus (HIV-1 and HIV-2), the two major viruses that cause AIDS
      in humans are retroviruses of the lentivirus genus. The genus includes arthritis
      encephalitis virus (CAEV) and Maedi-Visna virus (MVV), and a heterogeneous group
      of viruses known as small ruminant lentiviruses (SRLVs), affecting goat and
      sheep. Lentivirus genome integrates into the host DNA, causing persistent
      infection associated with a remarkable diversity during viral replication. Direct
      evidence of mixed infections with these two closely related SRLVs was found in
      both sheep and goats. The evidence of a genetic continuum with caprine and ovine
      field isolates demonstrates the absence of an efficient species barrier
      preventing cross-species transmission. In dual-infected animals, persistent
      infections with both CAEV and MVV have been described, and viral chimeras have
      been detected. This not only complicates animal trade between countries but
      favors the risk that highly pathogenic variants may emerge as has already been
      observed in the past in Iceland and, more recently, in outbreaks with virulent
      strains in Spain. SRLVs affecting wildlife have already been identified,
      demonstrating the existence of emergent viruses adapted to new hosts. Viruses
      adapted to wildlife ruminants may acquire novel biopathological properties which
      may endanger not only the new host species but also domestic ruminants and
      humans. SRLVs infecting sheep and goats follow a genomic evolution similar to
      that observed in HIV or in other lentiviruses. Lentivirus genetic diversity and
      host factors leading to the establishment of naturally occurring virulent versus
      avirulent infections, in addition to the emergence of new strains, challenge
      every aspect of SRLV control measures for providing efficient tools to prevent
      the transmission of diseases between wild ungulates and livestock. 

PMID- 23881278
TI  - History and current state of pathology in China.

PMID- 23881277
TI  - Baculovirus nuclear import: open, nuclear pore complex (NPC) sesame.
AB  - Baculoviruses are one of the largest viruses that replicate in the nucleus of
      their host cells. During infection, the rod-shape, 250-nm long nucleocapsid
      delivers its genome into the nucleus. Electron microscopy evidence suggests that
      baculoviruses, specifically the Alphabaculoviruses (nucleopolyhedroviruses) and
      the Betabaculoviruses (granuloviruses), have evolved two very distinct modes for
      doing this. Here we review historical and current experimental results of
      baculovirus nuclear import studies, with an emphasis on electron microscopy
      studies employing the prototypical baculovirus Autographa californica multiple
      nucleopolyhedrovirus infecting cultured cells. We also discuss the implications
      of recent studies towards theories of nuclear transport mechanisms. 

PMID- 23881279
TI  - Plakophilin-associated RNA-binding proteins in prostate cancer and their
      implications in tumor progression and metastasis.
AB  - Both plakophilins (PKP) 1 and 3 play a role in the progression of prostate
      cancer. The RNA-binding proteins (RBPs) GAP-SH3-binding protein (G3BP), fragile-X
      related protein 1 (FXR1), poly(A)-binding protein, cytoplasmic 1 (PABPC1), and up
      frameshift factor 1 (UPF1) are associated with PKP3. All these RBPs have an
      impact on RNA metabolism. Until recently, the PKP-associated RBPs have not been
      analyzed in prostate cancer. In the current study, we showed by affinity
      purification that the PKP3-associated RBPs were also binding partners of PKP1. We
      examined the expression of PKP1/3-associated RBPs and PKP1/3 in prostate cell
      lines, tumor-free prostate, and 136 prostatic adenocarcinomas by
      immunofluorescence and immunoblot. All four RBPs G3BP, FXR1, UPF1, and PABPC1
      were expressed in the glandular epithelium of the normal prostate. PKP1 and FXR1
      were strongly reduced in tumor tissues with Gleason score >7 and diminished
      expression of PKP1 and FXR1 also appeared to be associated with a metastatic
      phenotype. Additionally, the predominant nuclear localization of UPF1 in normal
      glandular cells and low grade tumors was switched to a more cytoplasmic pattern
      in carcinomas with Gleason score >7. Our findings suggest that PKP1 and FXR1 may
      have a tumor-suppressive function and are downregulated in more aggressive
      tumors. Collectively, PKP1/3-associated RBPs FXR1 and UPF1 may have a functional
      role in prostate cancer progression and metastasis and highlight the potential
      importance of posttranscriptional regulation of gene expression and nonsense
      mediated decay in cancer. 

PMID- 23881280
TI  - XPS and electrochemical impedance spectroscopy studies on effects of the
      porcelain firing process on surface and corrosion properties of two nickel
      chromium dental alloys.
AB  - The aim of this study was to evaluate the effects of a simulated porcelain firing
      process on the surface, corrosion behavior and cell culture response of two
      nickel-chromium (Ni-Cr) dental alloys. A Be-free alloy and a Be-containing alloy
      were tested. Before porcelain firing, as-cast specimens were examined for surface
      composition using X-ray photoelectron spectroscopy and metallurgical phases using
      X-ray diffraction. Corrosion behaviors were evaluated using electrochemical
      impedance spectroscopy. 3T3 fibroblasts were cultured and exposed indirectly to
      specimens. MTT assays were counted after 3 and 6 days. The cell culture mediums
      exposed to specimens were analyzed for metal ion release. After porcelain firing,
      similar specimens were examined for the same properties. In both as-cast and
      fired conditions, the Be-free Ni-Cr alloy showed significantly more resistance to
      corrosion than the Be-containing Ni-Cr alloy, which exhibited BeNi phase. After
      porcelain firing, the corrosion resistance of the Be-free Ni-Cr alloy decreased
      statistically, corresponding with evident decreases of Cr and Ni oxides on the
      alloy surface. Also, the alloy's MTT assay decreased significantly corresponding
      with an obvious increase of Ni-ion release after the firing. For the Be
      containing Ni-Cr alloy, the firing process led to increases of surface oxides and
      metallic Be, while its corrosion resistance and cell culture response were not
      significantly changed after porcelain firing. The results suggested that the
      corrosion resistance and biocompatibility of the Be-free Ni-Cr alloy decreased
      after porcelain firing, whereas the firing process had little effect on the same
      properties of the Be-containing Ni-Cr alloy.

PMID- 23881281
TI  - Curcumin induces apoptosis in human gastric carcinoma AGS cells and colon
      carcinoma HT-29 cells through mitochondrial dysfunction and endoplasmic reticulum
      stress.
AB  - In the present study, we investigate the effect of curcumin, a major active
      component isolated from rhizomes of Curcuma longa, on the cytotoxicity of three
      human carcinoma cell lines (AGS, HT-29 and MGC803) in gastrointestinal tract and
      a normal gastric epithelial cell line GES-1, and the mechanism of curcumin
      induced apoptosis. The results indicated that curcumin inhibited the
      gastrointestinal carcinoma cell growth in a dose-dependent manner and
      cytotoxicity was more towards the gastric carcinoma cell AGS and colon carcinoma
      cell HT-29 compared to normal gastric cell GES-1, and increased externalization
      of phosphatidylserine residue was observed by Annexin V/PI staining in the two
      cell lines. Treatment of AGS and HT-29 cells with curcumin enhanced the cleavage
      of procaspase-3, -7, -8 and -9. Meanwhile, curcumin induced endoplasmic reticulum
      (ER) stress and mitochondrial dysfunction as evidenced by up-regulation of
      CCAAT/enhancer binding protein homologous protein (CHOP), phosphorylation of JNK
      and down-regulation of SERCA2ATPase, release of cytochrome c, decrease of Bcl-2
      and reduction of mitochondrial membrane potential in both AGS and HT-29 cells.
      Overexpression of bax, total JNK, phospho-FADD and total FADD were also observed
      in curcumin-treated HT-29 cells. Moreover, curcumin decreased cytosolic and ER
      Ca(2+), but increased mitochondrial Ca(2+) in the two cell lines. 2
      Aminoethoxydiphenyl borate, an antagonist of inositol 1, 4, 5-triphosphate
      receptor, partly blocked curcumin-induced cytosolic Ca(2+) decrease in AGS and HT
      29 cells. Additionally, carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of
      mitochondrial Ca(2+) uptake, reversed curcumin-triggered AGS and HT-29 cells
      growth inhibition. siRNA to CHOP markedly reduced curcumin-induced apoptosis.
      These results suggest that curcumin can impact on ER stress and mitochondria
      functional pathways in AGS and HT-29 cells, death receptor pathway was also
      involved in curcumin-treated HT-29 cells, thus identifying specific well-defined
      molecular mechanisms that may be targeted by therapeutic strategies.

PMID- 23881282
TI  - Insights into metalloenzyme microenvironments: biomimetic metal complexes with a
      functional second coordination sphere.
AB  - Non-covalent interactions in the second coordination sphere of metalloenzymes
      play a significant role in determining activity and selectivity. The importance
      of these interactions is reflected in the increasing number of reports on model
      complexes with a functional second coordination sphere. These hybrid mimics were
      developed according to the strategies of modification with functional groups,
      combination with supramolecular hosts and coupling with polymers, to shed light
      on the role of non-covalent interactions in metalloenzyme catalysis. This review
      provides an overview of recent progress in this area. An introduction to native
      metalloenzymes with an emphasis on the second coordination sphere is also given. 

PMID- 23881283
TI  - Atomic force microscopy and near-field optical imaging of a spin transition.
AB  - We report on atomic force microscopy (AFM) and near-field scanning optical
      microscopy (NSOM) investigations of single crystals of the spin crossover complex
      {Fe(pyrazine)[Pt(CN)4]} across the first-order thermal spin transition. We
      demonstrate for the first time that the change in spin state can be probed with
      sub-micrometer spatial resolution through various topographic features extracted
      from AFM data. This original approach based on surface topography analysis should
      be easy to implement to any phase change material exhibiting sizeable electron
      lattice coupling. In addition, AFM images revealed specific topographic features
      in the crystals, which were correlated with the spatiotemporal evolution of the
      transition observed by far-field and near-field optical microscopies. 

PMID- 23881284
TI  - Actions of osteoporosis treatments on bone histomorphometric remodeling: a two
      fold principal component analysis.
AB  - This was the first study to apply principal component analysis method to bone
      histomorphometric parameters. The results corroborated teriparatide's distinct,
      yet different, mechanisms of action, which stimulate both bone formation and
      resorption. INTRODUCTION: This study consolidated bone histomorphometric
      parameters and compared the effects of two osteoporosis treatments on bone
      remodeling by using a principal component analysis (PCA). METHODS: Included in
      this analysis were postmenopausal women with osteoporosis who were treated with
      either teriparatide or alendronate and who completed transiliac bone biopsy at
      either 6 or 18 months in the randomized, double-blind Forteo Alendronate
      Comparator Trial. Eighteen histomorphometric parameters were grouped into
      formation and resorption categories. The first principal component of each
      category was estimated through the PCA. The summation of principal formation
      component (PFC) and principal resorption component (PRC) was calculated to
      represent the overall level of bone turnover. The difference between PFC and PRC
      was computed to determine the balance between formation and resorption. RESULTS:
      The PFC was significantly higher in the teriparatide group than in the
      alendronate group (P < 0.0001), while the PRC was numerically lower in the
      alendronate group (P = 0.18). The mean difference between the PFC and PRC was
      positive in the teriparatide group and negative in the alendronate group.
      CONCLUSIONS: Our approach of consolidating bone histomorphometric remodeling
      parameters corroborated the idea that the distinct, yet different, mechanisms of
      action of teriparatide treatment stimulate both bone formation and resorption,
      and alendronate treatment suppresses both bone formation and resorption.

PMID- 23881285
TI  - Conversion of a non-selective adenosine receptor antagonist into A3-selective
      high affinity fluorescent probes using peptide-based linkers.
AB  - Advances in fluorescence-based imaging technologies have helped propel the study
      of real-time biological readouts and analysis across many different areas. In
      particular the use of fluorescent ligands as chemical tools to study proteins
      such as G protein-coupled receptors (GPCRs) has received ongoing interest.
      Methods to improve the efficient chemical synthesis of fluorescent ligands remain
      of paramount importance to ensure this area of bioanalysis continues to advance.
      Here we report conversion of the non-selective GPCR adenosine receptor antagonist
      Xanthine Amine Congener into higher affinity and more receptor subtype-selective
      fluorescent antagonists. This was achieved through insertion and optimisation of
      a dipeptide linker between the adenosine receptor pharmacophore and the
      fluorophore. Fluorescent probe 27 containing BODIPY 630/650 (pK(D) = 9.12 +/-
      0.05 [hA3AR]), and BODIPY FL-containing 28 (pK(D) = 7.96 +/- 0.09 [hA3AR])
      demonstrated clear, displaceable membrane binding using fluorescent confocal
      microscopy. From in silico analysis of the docked ligand-receptor complexes of
      27, we suggest regions of molecular interaction that could account for the
      observed selectivity of these peptide-linker based fluorescent conjugates. This
      general approach of converting a non-selective ligand to a selective biological
      tool could be applied to other ligands of interest.

PMID- 23881286
TI  - Adult teleost heart expresses two distinct troponin C paralogs: cardiac TnC and a
      novel and teleost-specific ssTnC in a chamber- and temperature-dependent manner.
AB  - The teleost-specific whole genome duplication created multiple copies of genes
      allowing for subfunctionalization of isoforms. In this study, we show that the
      teleost cardiac Ca2+-binding troponin C (TnC) is the product of two distinct
      genes: cardiac TnC (cTnC, TnnC1a) and a fish-specific slow skeletal TnC (ssTnC,
      TnnC1b). The ssTnC gene is novel to teleosts as mammals have a single gene
      commonly referred as cTnC but which is also expressed in slow skeletal muscle. In
      teleosts, the data strongly indicate that these are two TnC genes are different
      paralogs. Because we determined that ssTnC exists across many teleosts but not in
      basal ray-finned fish (e.g., bichir), we propose that these paralogs are the
      result of an ancestral tandem gene duplication persisting only in teleosts.
      Quantification of mRNA levels was used to demonstrate distinct expression
      localization patterns of the paralogs within the chambers of the heart. In the
      adult zebrafish acclimated at 28 degrees C, ssTnC mRNA levels are twofold greater
      than cTnC mRNA levels in the atrium, whereas cTnC mRNA was almost exclusively
      expressed in the ventricle. Meanwhile, rainbow trout acclimated at 5 degrees C
      showed cTnC mRNA levels in both chambers significantly greater than ssTnC.
      Distinct responses to temperature acclimation were also quantified in both adult
      zebrafish and rainbow trout, with mRNA in both chambers shifting to express
      higher levels of cTnC in 18 degrees C acclimated zebrafish and 5 degrees C
      acclimated trout. Possible subfunctionalization of TnC isoforms may provide
      insight into how teleosts achieve physiological versatility in chamber-specific
      contractile properties.

PMID- 23881287
TI  - Rat Genome Database: a unique resource for rat, human, and mouse quantitative
      trait locus data.
AB  - The rat has been widely used as a disease model in a laboratory setting,
      resulting in an abundance of genetic and phenotype data from a wide variety of
      studies. These data can be found at the Rat Genome Database (RGD,
      http://rgd.mcw.edu/), which provides a platform for researchers interested in
      linking genomic variations to phenotypes. Quantitative trait loci (QTLs) form one
      of the earliest and core datasets, allowing researchers to identify loci
      harboring genes associated with disease. These QTLs are not only important for
      those using the rat to identify genes and regions associated with disease, but
      also for cross-organism analyses of syntenic regions on the mouse and the human
      genomes to identify potential regions for study in these organisms. Currently,
      RGD has data on >1,900 rat QTLs that include details about the methods and
      animals used to determine the respective QTL along with the genomic positions and
      markers that define the region. RGD also curates human QTLs (>1,900) and
      houses>4,000 mouse QTLs (imported from Mouse Genome Informatics). Multiple
      ontologies are used to standardize traits, phenotypes, diseases, and experimental
      methods to facilitate queries, analyses, and cross-organism comparisons. QTLs are
      visualized in tools such as GBrowse and GViewer, with additional tools for
      analysis of gene sets within QTL regions. The QTL data at RGD provide valuable
      information for the study of mapped phenotypes and identification of candidate
      genes for disease associations.

PMID- 23881288
TI  - Host-pathogen interactions during Mycobacterium tuberculosis infections.
AB  - The intimate and persistent connection between Mycobacterium tuberculosis and its
      human host suggests that the pathogen has evolved extensive mechanisms to evade
      eradication by the immune system. In particular, the organism has adapted to
      replicate within phagocytic cells, especially macrophages, which are specialized
      to kill microbes. Over the past decade of M. tuberculosis research, the means to
      manipulate both the organism and the host has ushered in an exciting time that
      has uncovered some of the mechanisms of the innate macrophage-pathogen
      interactions that lie at the heart of M. tuberculosis pathogenesis, though many
      interactions likely still await discovery. In this chapter, we will delve into
      some of these advances, with an emphasis on the interactions that occur on the
      cellular level when M. tuberculosis cells encounter macrophages. In particular,
      we focus on two major aspects of M. tuberculosis biology regarding the proximal
      physical interface between the bacterium and host, namely the interactions with
      the phagosomal membrane as well as the distinctive mycobacterial cell wall.
      Importantly, some of the emerging paradigms in M. tuberculosis pathogenesis and
      host response represent common themes in bacterial pathogenesis, such as the role
      of host cell membrane perforation in intracellular survival and host response.
      However, the array of unique bacterial lipid mediators and their interaction with
      host cells highlights the unique biology of this persistent pathogen. 

PMID- 23881290
TI  - Potential interactions with anticancer agents: a cross-sectional study.
AB  - BACKGROUND: Patients with cancer are particularly susceptible to drug
      interactions (DIs), but the extent of the problem has received limited attention.
      We aimed to evaluate the frequency of interactions with anticancer agents in a
      group of cancer patients. METHODS: The study was performed in a Belgian teaching
      hospital. One hundred and twenty-two patients with solid malignancies were
      included. A comprehensive drug history was performed by a clinical pharmacist.
      Three renowned DI compendia were used to identify DIs. RESULTS: Forty-one
      potential interactions involving an anticancer agent and considered to be
      clinically significant were identified among 25% of patients. The anticancer
      drugs mostly involved were cisplatin and methotrexate, and the most frequent co
      medications involved were vitamin K antagonists, proton pump inhibitors and
      diuretics. In the majority of cases, the potential adverse consequence was
      increased toxicity of the anticancer agent and/or of the co-medication. Less than
      10% of DIs were identified by the three compendia. CONCLUSIONS: Preventive
      measures should be taken to avoid increased toxicity or decreased efficacy of the
      drugs. Most of the time, this simply involves surveillance of biological or
      clinical parameters. Collaboration with a clinical pharmacist may be useful for
      the prescribing physician.

PMID- 23881291
TI  - Bioimpedance and impedance vector patterns as predictors of league level in male
      soccer players.
AB  - PURPOSE: Bioelectrical-impedance standards (resistance, reactance, and phase
      angle) are well established for the normal population or in the clinical setting
      and are considered indicators for cell mass, cell function, and hydration status.
      However, such standards do not exist for the male soccer population. Therefore,
      the goal of the current investigation was to provide a set of bioelectrical
      impedance data of a large sample of soccer players with different performance
      levels. METHODS: A sample of 893 players, registered in all Italian soccer
      divisions, was divided into 5 groups according to their performance level. Whole
      body impedance measurements were performed during the first half of the
      competitive period. Besides estimation of body composition, bioelectrical
      impedance vector analysis (BIVA) was performed. BIVA does not depend on equations
      and displays differences in hydration and body-cell mass (BCM). Individual
      vectors can be classified by using the 50%, 75%, and 95% tolerance ellipse.
      RESULTS: In comparison with the other divisions and the normal population, the
      mean vector of the elite level showed a shift to the left (P < .001). Compared
      with the elite level, players of a lower performance level had lower phase
      angles, BCM, and fat-free mass. CONCLUSIONS: In conclusion, soccer players belong
      to a specific population. Muscle mass and function, as indicated by BCM and phase
      angle, increase with increasing performance level. The soccer-specific tolerance
      ellipses might be used for classifying individual vectors and to define target
      regions for low-level players.

PMID- 23881292
TI  - Accelerated thermokarst formation in the McMurdo Dry Valleys, Antarctica.
AB  - Thermokarst is a land surface lowered and disrupted by melting ground ice.
      Thermokarst is a major driver of landscape change in the Arctic, but has been
      considered to be a minor process in Antarctica. Here, we use ground-based and
      airborne LiDAR coupled with timelapse imaging and meteorological data to show
      that 1) thermokarst formation has accelerated in Garwood Valley, Antarctica; 2)
      the rate of thermokarst erosion is presently ~ 10 times the average Holocene
      rate; and 3) the increased rate of thermokarst formation is driven most strongly
      by increasing insolation and sediment/albedo feedbacks. This suggests that
      sediment enhancement of insolation-driven melting may act similarly to expected
      increases in Antarctic air temperature (presently occurring along the Antarctic
      Peninsula), and may serve as a leading indicator of imminent landscape change in
      Antarctica that will generate thermokarst landforms similar to those in Arctic
      periglacial terrains. 

PMID- 23881289
TI  - Diphenyl diselenide prevents cortico-cerebral mitochondrial dysfunction and
      oxidative stress induced by hypercholesterolemia in LDL receptor knockout mice.
AB  - Recent studies have indicated a causal link between high dietary cholesterol
      intake and brain oxidative stress. In particular, we have previously shown a
      positive correlation between elevated plasma cholesterol levels, cortico-cerebral
      oxidative stress and mitochondrial dysfunction in low density lipoprotein
      receptor knockout (LDLr(-/-)) mice, a mouse model of familial
      hypercholesterolemia. Here we show that the organoselenium compound diphenyl
      diselenide (PhSe)2 (1 mg/kg; o.g., once a day for 30 days) significantly blunted
      the cortico-cerebral oxidative stress and mitochondrial dysfunction induced by a
      hypercholesterolemic diet in LDLr(-/-) mice. (PhSe)2 effectively prevented the
      inhibition of complex I and II activities, significantly increased the reduced
      glutathione (GSH) content and reduced lipoperoxidation in the cerebral cortex of
      hypercholesterolemic LDLr(-/-) mice. Overall, (PhSe)2 may be a promising molecule
      to protect against hypercholesterolemia-induced effects on the central nervous
      system, in addition to its already demonstrated antiatherogenic effects.

PMID- 23881293
TI  - Changes in resting-state fMRI in vestibular neuritis.
AB  - Vestibular neuritis (VN) is a sudden peripheral unilateral vestibular failure
      with often persistent head movement-related dizziness and unsteadiness.
      Compensation of asymmetrical activity in the primary peripheral vestibular
      afferents is accomplished by restoration of impaired brainstem vestibulo-ocular
      and vestibulo-spinal reflexes, but presumably also by changing cortical
      vestibular tone imbalance subserving, e.g., spatial perception and orientation.
      The aim of this study was to elucidate (i) whether there are changes of cerebral
      resting-state networks with respect to functional interregional connectivity
      (resting-state activity) in VN patients and (ii) whether these are related to
      neurophysiological, perceptual and functional parameters of vestibular-induced
      disability. Using independent component analysis (ICA), we compared resting-state
      networks between 20 patients with unilateral VN and 20 age- and gender-matched
      healthy control subjects. Patients were examined in the acute VN stage and after
      3 months. A neural network (component 50) comprising the parietal lobe, medial
      aspect of the superior parietal lobule, posterior cingulate cortex, middle
      frontal gyrus, middle temporal gyrus, parahippocampal gyrus, anterior cingulate
      cortex, insular cortex, caudate nucleus, thalamus and midbrain was modulated
      between acute VN patients and healthy controls and in patients over time. Within
      this network, acute VN patients showed decreased resting-state activity (ICA) in
      the contralateral intraparietal sulcus (IPS), in close vicinity to the
      supramarginal gyrus (SMG), which increased after 3 months. Resting-state activity
      in IPS tended to increase over 3 months in VN patients who improved with respect
      to functional parameters of vestibular-induced disability (VADL). Resting-state
      activity in the IPS was not related to perceptual (subjective visual vertical) or
      neurophysiological parameters of vestibular-induced disability (e.g., gain of
      vestibulo-ocular reflex, caloric responsiveness, postural sway). VN leads to a
      change in resting-state activity of the contralateral IPS adjacent to the SMG,
      which reverses during vestibular compensation over 3 months. The ventral
      intraparietal area in the IPS contains multimodal regions with directionally
      selective responses to vestibular stimuli making them suitable for participating
      in spatial orientation and multisensory integration. The clinical importance is
      indicated by the fact that the increase in resting-state activity tended to be
      larger in those patients with only little disability at the follow-up
      examination. This may indicate powerful restitution-related or compensatory
      cortical changes in resting-state activity. 

PMID- 23881294
TI  - The Big Five default brain: functional evidence.
AB  - Recent neuroimaging studies have provided evidence that different dimensions of
      human personality may be associated with specific structural neuroanatomic
      correlates. Identifying brain correlates of a situation-independent personality
      structure would require evidence of a stable default mode of brain functioning.
      In this study, we investigated the correlates of the Big Five personality
      dimensions (Extraversion, Neuroticism, Openness/Intellect, Agreeableness, and
      Conscientiousness) and the default mode network (DMN). Forty-nine healthy adults
      completed the NEO-Five Factor. The results showed that the Extraversion (E) and
      Agreeableness (A) were positively correlated with activity in the midline core of
      the DMN, whereas Neuroticism (N), Openness (O), and Conscientiousness (C) were
      correlated with the parietal cortex system. Activity of the anterior cingulate
      cortex was positively associated with A and negatively with C. Regions of the
      parietal lobe were differentially associated with each personality dimension. The
      present study not only confirms previous functional correlates regarding the Big
      Five personality dimensions, but it also expands our knowledge showing the
      association between different personality dimensions and specific patterns of
      brain activation at rest. 

PMID- 23881295
TI  - Organization of afferents to the striatopallidal systems in the fire-bellied toad
      Bombina orientalis.
AB  - The cerebral hemispheres of amphibians display paired dorsal and ventral striatum
      (commonly referred to as striatum proper and nucleus accumbens, respectively).
      Each striatal region is proposed to be closely associated with a pallidal
      structure located caudal to it to form a striatopallidal system. In the present
      study, afferents to the dorsal and ventral striatopallidal systems of the fire
      bellied toad (Bombina orientalis) were investigated using the neuronal tracer
      biocytin. A quantitative analysis of the topographical distribution of afferent
      neurons from the thalamus and posterior tubercle/ventral tegmentum was
      emphasised. The main results show that inputs to the two striatopallidal systems
      originate from distinct dorsal thalamic nuclei, with dorsal and ventral
      striatopallidal afferent neurons favouring strongly the lateral/central and
      anterior thalamic nuclei, respectively. However, afferent neuron distribution in
      the dorsal thalamus does not differ in the rostrocaudal axis of the brain.
      Afferent neurons from the posterior tubercle and ventral tegmentum, on the other
      hand, are organised topographically along the rostrocaudal axis. About 85 % of
      afferent neurons to the dorsal striatopallidal system are located rostrally in
      the posterior tubercle, while 75 % of afferent neurons to the ventral
      striatopallidal system are found more caudally in the ventral tegmentum. This
      difference is statistically significant and confirms the presence of distinct
      mesostriatal pathways in an amphibian. These findings demonstrate that an
      amphibian brain displays striatopallidal systems integrating parallel streams of
      sensory information potentially under the influence of distinct ascending
      mesostriatal pathways. 

PMID- 23881296
TI  - Theoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2
      inhibitors: insight into structure-based inhibitor design.
AB  - LIM kinases (LIMKs), downstream of Rho-associated protein kinases (ROCKs) and p21
      activated protein kinases (PAKs), are shown to be promising targets for the
      treatment of cancers. In this study, the inhibition mechanism of 41
      pyrrolopyrimidine derivatives as LIMK2 inhibitors was explored through a series
      of theoretical approaches. First, a model of LIMK2 was generated through
      molecular homology modeling, and the studied inhibitors were docked into the
      binding active site of LIMK2 by the docking protocol, taking into consideration
      the flexibility of the protein. The binding poses predicted by molecular docking
      for 17 selected inhibitors with different bioactivities complexed with LIMK2
      underwent molecular dynamics (MD) simulations, and the binding free energies for
      the complexes were predicted by using the molecular mechanics/generalized born
      surface area (MM/GBSA) method. The predicted binding free energies correlated
      well with the experimental bioactivities (r(2) = 0.63 or 0.62). Next, the free
      energy decomposition analysis was utilized to highlight the following key
      structural features related to biological activity: (1) the important H-bond
      between Ile408 and pyrrolopyrimidine, (2) the H-bonds between the inhibitors and
      Asp469 and Gly471 which maintain the stability of the DFG-out conformation, and
      (3) the hydrophobic interactions between the inhibitors and several key residues
      (Leu337, Phe342, Ala345, Val358, Lys360, Leu389, Ile408, Leu458 and Leu472).
      Finally, a variety of LIMK2 inhibitors with a pyrrolopyrimidine scaffold were
      designed, some of which showed improved potency according to the predictions. Our
      studies suggest that the use of molecular docking with MD simulations and free
      energy calculations could be a powerful tool for understanding the binding
      mechanism of LIMK2 inhibitors and for the design of more potent LIMK2 inhibitors.

PMID- 23881297
TI  - Reversible photoluminescence quenching of CdSe/ZnS quantum dots embedded in
      porous glass by ammonia vapor.
AB  - The photoluminescence response of semiconductor CdSe/ZnS quantum dots embedded in
      a borosilicate porous glass matrix to exposure to ammonia vapor is investigated.
      The formation of surface complexes on the quantum dots results in quenching of
      the photoluminescence and a shortening of the luminescence decay time. The
      process is reversible, desorption of ammonia molecules from the quantum dot
      surface causes the photoluminescence to recover. The sensitivity of the quantum
      dot luminescence intensity and decay time to the interaction time and the
      reversibility of the photoluminescence changes make the CdSe/ZnS quantum dots in
      porous glass system a candidate for use as an optical sensor of ammonia. 

PMID- 23881298
TI  - CD4+CD25+Foxp3 regulatory T cells and vascular dysfunction in hypertension.
AB  - Endothelial dysfunction plays a key role in the development and progression of
      cardiovascular disease. In patients with hypertension, endothelial dysfunction is
      characterized by a decrease of vasodilator factors release. Recent evidence
      highlights the involvement of regulatory T cell in the cardiovascular physiology
      and pathology. An increasing body of data suggest that an imbalance in the immune
      system triggers inflammation and compromises the cardiovascular homeostasis. In
      this mini-review, we will highlight the role of immune regulatory T cells in
      hypertension-induced vascular dysfunction. 

PMID- 23881299
TI  - High circulatory titer of platelet-associated autoantibodies in childhood onset
      schizophrenia and its diagnostic implications.
AB  - BACKGROUND: It has been suggested that the etiology of schizophrenia, in a
      distinct group of patients, originates from an autoimmune reaction against
      platelets. Previous studies have demonstrated significantly higher blood titers
      of platelet-associated autoantibodies (PAA) in adult schizophrenia patients as
      compared to normal healthy subjects. In addition, young adult schizophrenia
      patients at their early stages of the disorder displayed higher PAA titers than
      older patients with longer duration of the disorder. AIM: To assess the blood
      titers of PAA in children with schizophrenia as compared to matched control
      subjects without psychotic disorders, as a possible diagnostic parameter.
      METHODS: Twenty-nine children with DSM-IV schizophrenia in the active psychotic
      state, with an age range of 6-12 years (mean +/- SD: 9.6 +/- 1.5 years), with
      average Positive and Negative Syndrome Scale scores of 108 +/- 19.2, were
      assessed. The control group consisted of 25 children with DSM-IV conduct disorder
      in a similar age range of 5-12 years (mean +/- SD: 9.5 +/- 1.6 years). The blood
      titers of PAA were evaluated using an optimized ELISA test, expressed by a linear
      optical density (OD) scale. The blood samples of all participants were tested
      anonymously and were scored under a code number. A test recording above 1.4 OD
      units was predefined as positive. RESULTS: The titers of PAA of children with
      schizophrenia (1.9 +/- 0.5 OD units, range: 0.7-2.44 units) were significantly (p
      < 0.00001) higher than those of the control group (1.0 +/- 0.4 OD units, range:
      0.45-2.28 units). In 83% of the children with schizophrenia (24 out of the 29
      patients) a positive test, i.e. OD >1.4, was detected. In contrast, in the
      control group, only 12% (3 of the 25 subjects) displayed a positive test, p <
      0.00001. CONCLUSIONS: High titers of PAA in children with schizophrenia as
      compared with nonpsychotic controls may indicate an active autoimmune process in
      the early onset of schizophrenia. The PAA level may therefore provide a
      supportive diagnostic biomarker for childhood schizophrenia.

PMID- 23881300
TI  - Computed diffusion-weighted imaging using 3-T magnetic resonance imaging for
      prostate cancer diagnosis.
AB  - OBJECTIVE: To assess the efficacy of computed diffusion-weighted images (cDWIs)
      of b = 2000 s/mm(2) (cDWI2000) generated from DWIs of b = 0 and 1000 for prostate
      cancer (PCa) diagnosis in comparison with that of measured original DWIs of b =
      1000 (mDWI1000) and b = 2000(mDWI2000) using 3-T MRI. METHODS: Eighty patients
      who underwent a preoperative MRI examination, including T2WI and DWI (b = 0,
      1000, 2000 s/mm(2)), were enrolled in this study. Four combinations of images,
      protocol A (T2WI alone), B (T2WI + mDWI1000), C (T2WI + mDWI2000) and D (T2WI +
      cDWI2000), were assessed for their diagnostic capability. Areas under the
      receiver operating characteristic curve (Az) and diagnostic performance were
      evaluated, as well as contrast ratios (CR) between cancerous and non-cancerous
      lesions for each DWI. RESULTS: The highest CR was obtained with cDWI2000 (0.29 +/
      0.16). Sensitivity, specificity, accuracy, and Az of the protocols were: A: 66.3
      %, 59.4 %, 63.0 %, 0.67; B: 82.6 %, 62.0 %, 72.5 %, 0.80; C: 84.1 %, 66.5 %, 75.5
      %, 0.86; D: 83.2 %, 70.0 %, 76.6 %, and 0.84, respectively The specificities and
      accuracies of protocol C and D were significantly higher than those of protocol B
      (P < 0.05). CONCLUSION: cDWI2000 appears to be more effective than mDWI1000, and
      at least as effective as mDWI2000 for PCa diagnosis.

PMID- 23881301
TI  - Acoustic radiation force impulse (ARFI) in the evaluation of the renal
      parenchymal stiffness in paediatric patients with vesicoureteral reflux:
      preliminary results.
AB  - OBJECTIVES: To prospectively evaluate acoustic radiation force impulse (ARFI)
      imaging of the kidneys in children with and without chronic renal disease.
      METHODS: Twenty-eight children (age range 9-16 years) with primary or secondary
      vesicoureteral reflux (>= grade III) underwent scintigraphy and ultrasound with
      ARFI. Kidneys were divided-according to scintigraphy-into "affected" and
      "contralateral"; the results were compared with 16 age-matched healthy subjects.
      An ARFI value, expressed as speed (m/s) of wave propagation through the tissue,
      was calculated for each kidney through the mean of the values obtained at the
      upper, middle and lower third. The Wilcoxon test was used; P values <0.05 were
      considered statistically significant. RESULTS: The mean ARFI values obtained in
      the "affected" kidneys (5.70 +/- 1.71 m/s) were significantly higher than those
      measured in both "contralateral" (4.09 +/- 0.97, P < 0.0001) and "healthy"
      kidneys (3.13 +/- 0.09, P < 0.0001). The difference between values in the
      "contralateral" kidneys and "healthy" ones was significant (P < 0.0001). The
      "affected" kidneys with secondary reflux had mean ARFI values (6.59 +/- 1.45)
      significantly higher than those with primary reflux (5.35 +/- 1.72). CONCLUSIONS:
      ARFI values decrease from kidneys with secondary vesicoureteral reflux to kidneys
      with primary reflux to unaffected kidneys contralateral to reflux to normal
      kidneys.

PMID- 23881302
TI  - A new-generation, low-permeability flow diverting device for treatment of
      saccular aneurysms.
AB  - OBJECTIVES: We report a preclinical comparative study of a 96-strand braided flow
      diverter. METHODS: The 96-strand braided device was compared with the currently
      commercially available flow diverter with 48 strands. The devices were implanted
      across the neck of 12 elastase-induced aneurysms in New Zealand White rabbits and
      followed for 1 and 3 months (n = 6 respectively). Aneurysm occlusion rates,
      parent artery stenosis and patency of jailed branch occlusions were assessed by
      angiography, histology and scanning electron microscopy studies. RESULTS: It was
      feasible to navigate and implant the 96-strand device over the aneurysm orifice
      in all cases. At follow-up two aneurysms in the 48-strand vs. one in the 96
      strand group were not occluded. This aneurysm from the 96-strand group however
      had a tracheal branch arising from the sac and showed a reverse remodelling of
      the vascular pouch at 3 months. In the occluded aneurysms, the parent artery was
      always completely reconstructed and the aneurysm orifice was sealed with
      neointimal tissue. No in-stent stenosis or jailed branch artery occlusion was
      observed. CONCLUSIONS: The 96-strand flow diverter proved to be safe,
      biocompatible and haemodynamically effective, induced stable occlusion of
      aneurysms and led to reverse remodelling of the parent artery. KEY POINTS: * Flow
      diversion has been introduced to improve endovascular treatment of cerebral
      aneurysms * A new low-permeability flow diverter is feasible for parent artery
      reconstruction. * The Silk 96 flow diverter appears effective at inducing
      aneurysm healing. * The covered branches remained patent at follow-up.

PMID- 23881303
TI  - Persistent ascites after liver transplantation: etiology, treatment and impact on
      survival.
AB  - BACKGROUND: Persistent ascites is an uncommon complication after orthotopic liver
      transplantation (OLT). Data on etiology, treatment and outcome are limited.
      MATERIAL AND METHODS: Data on 691 orthotopic liver transplantations in 585
      patients were reviewed retrospectively. Patients with persistent ascites (longer
      than 4 weeks after successful liver transplantation) were selected and for each
      case two controls (no ascites after 4 weeks) were assigned and matched for age,
      sex, etiology of liver disease and pre-transplantation Child-Pugh-score/MELD
      score. RESULTS: Persistent ascites for more than 4 weeks after liver
      transplantation was present in 5.6% (33/585) patients and 4.8% (33/691) cases for
      a mean of 159 +/- 174 days. The most common underlying reason was bacterial or
      fungal peritonitis (69.7%; 23/33). Other etiologies included renal dysfunction
      (6%; 2/33), obstruction of the portal vein (3%; 1/33), and obstruction of the
      liver vein outflow (12%; 4/33); the etiology was unclear in 9% (3/33). Liver
      function tests, c-reactive protein levels and parameters of renal function at 4
      weeks post liver transplantation did not differ significantly between cases and
      controls. Patients with persistent ascites had refractory ascites before OLT
      significantly more often than controls. The 1-year survival rate was 92.3% for
      controls vs. 75.8% for cases (Kaplan Meier estimate p<0.05). Treatment
      (paracentesis; diuretic medical treatment; antibiotic treatment for patients with
      peritonitis or bacterial infection; radiologic intervention in cases of
      underlying vascular obstruction) resolved ascites in 72.7% (24/33 patients).
      Ascites due to infection was treated successfully significantly more often than
      all other groups (p<0.05). CONCLUSIONS: Persistent ascites after liver
      transplantation is rare, but is associated with reduced 1-year survival. The
      underlying mechanisms are diverse, abdominal bacterial infection being the most
      common cause. The majority of cases can be successfully treated.

PMID- 23881304
TI  - Stimuli responsive materials.

PMID- 23881305
TI  - Freeze-anneal-thaw cycling of unilamellar liposomes: effect on encapsulation
      efficiency.
AB  - PURPOSE: Freeze-thaw cycling is an important processing step in the preparation
      of liposomes that leads to the encapsulation of drug molecules. There is
      considerable variability in the number of freeze-thaw cycles reported in the
      literature. This work is designed to aid in liposomal formulation design by
      gaining an insight into the drug encapsulation process and an understanding of
      liposome stabilization during various thawing conditions. METHODS: The effects of
      different thawing temperatures, as well as "annealing" at subzero temperatures on
      a liposome formulation, are reported here. RESULTS: Two freeze-anneal-thaw
      (FANNT) cycles (freezing to -196 degrees C, annealing at -1.4 degrees C for ~30
      min, thawing at 65 degrees C) resulted in the maximum predicted encapsulation
      efficiency without causing any significant change in particle size or zeta
      potential. Annealing at -22 degrees C was shown to be destabilizing due to
      limited hydration of the liposomes in the frozen state. CONCLUSIONS: It was shown
      that two important processes are occurring during the FANNT cycling that affect
      liposome encapsulation efficiency. The first is drug diffusion in the frozen
      state and the second is fusion/destabilization of the liposomes. This is the
      first report on the annealing of liposomes and understanding the mechanism of
      drug encapsulation using the freeze-thaw cycling method.

PMID- 23881307
TI  - VPREB1 deletions occur independent of lambda light chain rearrangement in
      childhood acute lymphoblastic leukemia.

PMID- 23881308
TI  - Changes in routine health behaviors following late-life bereavement: a systematic
      review.
AB  - This systematic review examines the relationship between late-life spousal
      bereavement and changes in routine health behaviors. We review six behavioral
      domains/modifiable risk factors that are important for maintaining health among
      elderly populations: physical activity, nutrition, sleep quality, alcohol
      consumption, tobacco use, and body weight status. Thirty-four articles were
      identified, derived from 32 studies. We found strong evidence for a relationship
      between bereavement and nutritional risk and involuntary weight loss, and
      moderate evidence for impaired sleep quality and increased alcohol consumption.
      There was mixed evidence for a relationship between bereavement and physical
      activity. We identify several methodological shortcomings, and describe the
      clinical implications of this review for the development of preventive
      intervention strategies. 

PMID- 23881310
TI  - The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology.
AB  - There are many reviews of pancreatic acinar cell function and also of pancreatic
      duct function, but there is an almost total absence of synthetic reviews bringing
      the integrated functions of these two vitally and mutually interdependent cells
      together. This is what we have attempted to do in this chapter. In the first
      part, we review the normal integrated function of the acinar-ductal system, with
      particular emphasis on how regulation of one type of cell also influences the
      other cell type. In the second part, we review a range of pathological processes,
      particularly those involved in acute pancreatitis (AP), an often-fatal human
      disease in which the pancreas digests itself, in order to explore how malfunction
      of one of the cell types adversely affects the function of the other. 

PMID- 23881309
TI  - Acceptance as a mediator in internet-delivered acceptance and commitment therapy
      and cognitive behavior therapy for tinnitus.
AB  - Despite demonstrated efficacy of behavioral and cognitive techniques in treating
      the impact of tinnitus (constant ringing in the ears), little is known about the
      mechanisms by which these techniques achieve their effect. The present study
      examined acceptance of tinnitus as a potential mediator of treatment changes on
      global tinnitus severity in internet-delivered acceptance and commitment therapy
      (iACT) and internet-delivered cognitive behavior therapy (iCBT). Data from 67
      participants who were distressed by tinnitus and who were randomly assigned to 1
      of the 2 treatments were analyzed using a multilevel moderated mediation model.
      We predicted that acceptance as measured with the two subscales of the tinnitus
      acceptance questionnaire (i.e., activity engagement and tinnitus suppression)
      would mediate the outcome in iACT, but not in iCBT. Results provided partial
      support to the notion that mediation was moderated by treatment: tinnitus
      suppression mediated changes in tinnitus severity in iACT, but not in iCBT.
      However, inconsistent with the view that the treatments worked through different
      processes of change, activity engagement mediated treatment changes across both
      iACT and iCBT. Acceptance is identified as a key source of therapeutic change in
      behavioral-based treatments for tinnitus. 

PMID- 23881311
TI  - A novel 'pipeline' system for downstream preparation of therapeutic monoclonal
      antibodies.
AB  - A novel 'pipeline' system for the preparation of therapeutic monoclonal
      antibodies (mAb) in a non-GMP compliant environment has been developed. We used
      sterile silica-gel pipes to connect individual process units, in order to form a
      fully-enclosed and seamlessly connected system. This 'pipeline' system was used
      to implement downstream preparation processes for a humanized anti-CD146 mAb,
      huAA98, which is a therapeutic mAb generated to inhibit cancer-related
      angiogenesis. The quality assessment of the huAA98 end-product indicated that
      endotoxin levels were 0.016 EU/ml, protein A levels were 1.08 ng/ml and host cell
      protein (HCP) was undetectable. Thus, all measures were below the clinical
      criteria set by the Chinese Pharmacopoeia (Edition 2010). Having passed our proof
      of-concept test, this 'pipeline' system can be used as a universal platform for
      the preparation of mAbs suitable for pre-clinical studies, in a non-GMP compliant
      laboratory environment. 

PMID- 23881312
TI  - Hydration and saccharification of cellulose Ibeta, II and III(I) at increasing
      dry solids loadings.
AB  - Crystalline cellulose Ibeta (Avicel) was chemically transformed into cellulose II
      and III(I) producing allomorphs with similar crystallinity indices (ATR-IR and
      XRD derived). Saccharifications by commercial cellulases at arrayed solids
      loadings showed cellulose III(I) was more readily hydrolysable and less
      susceptible to increased dry solids levels than cellulose Ibeta and II. Analysis
      by dynamic vapor sorption revealed cellulose II has a distinctively higher
      absorptive capacity than cellulose I and III(I). When equally hydrated (g water/g
      cellulose), low-field nuclear magnetic resonance (LF-NMR) relaxometry showed that
      cellulose II, on average, most constrained water while cellulase III(I) left the
      most free water. LF-NMR spin-spin relaxation time distribution profiles
      representing distinct water pools suggest cellulose III(I) had the most
      restricted pool and changes in water distribution during enzymatic
      saccharification were most dramatic with respect to cellulose III(I) compared to
      celluloses Ibeta and II.

PMID- 23881313
TI  - Expression of a lipase on the cell-surface of Escherichia coli using the OmpW
      anchoring motif and its application to enantioselective reactions.
AB  - Microbial-surface display is the expression of proteins or peptides on the
      surface of cells by fusing an appropriate protein as an anchoring motif. Here,
      the outer membrane protein W (OmpW) was selected as a fusion partner for
      functional expression of Pseudomonas fluorescence SIK W1 lipase (TliA) on the
      cell-surface of Escherichia coli. Localization of the truncated OmpW-TliA fusion
      protein on the cell-surface was confirmed by immunoblotting and functional assay
      of lipase activity. Enantioselective hydrolysis of rac-phenylethyl butanoate by
      the displayed lipase resulted in optically active (R)-phenyl ethanol with 96%
      enantiomeric excess and 44% of conversion in 5 days. Thus, a small outer membrane
      protein OmpW, is a useful anchoring motif for displaying an active enzyme of ~50
      kDa on the cell-surface and the surface-displayed lipase can be employed as an
      enantioselective biocatalyst in organic synthesis.

PMID- 23881314
TI  - Mechanical stimulation and the presence of neighboring cells greatly affect
      migration of human mesenchymal stem cells.
AB  - There are few studies regarding the effects of mechanical stimulation on cell
      migration although biochemical factors have been widely studied. We have
      investigated the effects of intermittent hydrostatic pressure (IHP) on
      mesenchymal stem cell migration with or without neighboring endothelial cells
      (EC). IHP promoted MSCs migration and the neighboring ECs helped with this.
      However, when IHP was applied to MSCs cultured with ECs, the opposite effect was
      observed. The concentration of stromal-derived factor-1 culture in medium was
      measured to explain the obtained results. SDF-1 concentration increased as IHP
      increased when MSCs were cultured alone. However, it decreased as IHP increased
      when MSCs and ECs were co-cultured. These results indicate that the mechanical
      environment should be considered when studying the migration of a cell type along
      with its biochemical environment.

PMID- 23881315
TI  - Autophagy and its implication in Chinese hamster ovary cell culture.
AB  - Chinese hamster ovary (CHO) cells, that are widely used for production of
      therapeutic proteins, are subjected to apoptosis and autophagy under the stresses
      induced by conditions such as nutrient deprivation, hyperosmolality and addition
      of sodium butyrate. To achieve a cost-effective level of production, it is
      important to extend the culture longevity. Until now, there have been numerous
      studies in which apoptosis of recombinant CHO (rCHO) cells was inhibited,
      resulting in enhanced production of therapeutic proteins. Recently, autophagy in
      rCHO cells has drawn attention because it can be genetically and chemically
      controlled to increase cell survival and productivity. Autophagy is a global
      catabolic process which involves multiple pathways and genes that regulate the
      lysosomal degradation of intracellular components. A simultaneous targeting of
      anti-apoptosis and pro-autophagy could lead to more efficient protection of cells
      from stressful culture conditions. In this regard, it is worthwhile to have a
      detailed understanding of the autophagic pathway, in order to select appropriate
      genes and chemical targets to manage autophagy in rCHO cells, and thus to enhance
      the production of therapeutic proteins.

PMID- 23881316
TI  - Regulation, evolution, and functionality of flavonoids in cereal crops.
AB  - Flavonoids are plant secondary metabolites that contribute to the adaptation of
      plants to environmental stresses, including resistance to abiotic and biotic
      stress. Flavonoids are also beneficial for human health and depress the
      progression of some chronic diseases. The biosynthesis of flavonoids, which
      belong to a large family of phenolic compounds, is a complex metabolic process
      with many pathways that produce different metabolites, controlled by key enzymes.
      There is limited knowledge about the composition, biosynthesis and regulation of
      flavonoids in cereals. Improved understanding of the accumulation of flavonoids
      in cereal grains would help to improve human nutrition through these staple
      foods. The biosynthesis of flavonoids, scope for altering the flavonoid
      composition in cereal crops and benefits for human nutrition are reviewed here.

PMID- 23881317
TI  - Immobilization of tomato (Lycopersicon esculentum) pectinmethylesterase in
      calcium alginate beads and its application in fruit juice clarification.
AB  - Clarity of fruit juices is desirable to maintain an aesthetically pleasing
      quality and international standards. The most commonly used enzymes in juice
      industries are pectinases. A partially-purified pectinmethylesterase from tomato
      was entrapped in calcium alginate beads and used for juice clarification. The
      activity yield was maximum at 1 % (w/v) CaCl2 and 2.5 % (w/v) alginate. The
      immobilized enzyme retained ~55 % of its initial activity (5.7 * 10(-2) units)
      after more than ten successive batch reactions. The Km, pH and temperature optima
      were increased after immobilization. The most effective clarification of fruit
      juice (%T620 ~60 %) by the immobilized enzyme was at 4  degrees C with a holding
      time of 20 min. The viscosity dropped by 56 % and the filterability increased by
      260 %. The juice remains clear after 2 months of storage at 4  degrees C.

PMID- 23881318
TI  - Metabolic engineering strategies for improving xylitol production from
      hemicellulosic sugars.
AB  - Xylitol is a five-carbon sugar alcohol with potential for use as a sweetener.
      Industrially, xylitol is currently produced by chemical hydrogenation of D-xylose
      using Raney nickel catalysts and this requires expensive separation and
      purification steps as well as high pressure and temperature that lead to
      environmental pollution. Highly efficient biotechnological production of xylitol
      using microorganisms is gaining more attention and has been proposed as an
      alternative process. Although the biotechnological method has not yet surpassed
      the advantages of chemical reduction in terms of yield and cost, various
      strategies offer promise for the biotechnological production of xylitol. In this
      review, the focus is on the most recent developments of the main metabolic
      engineering strategies for improving the production of xylitol.

PMID- 23881319
TI  - Construction of a tightly-controlled expression system for use in Pseudomonas.
AB  - Transcriptional analysis of czcCBA gene cluster in Pseudomonas aeruginosa PAO1
      revealed that the promoter of this operon is tightly controlled by Zn. The
      promoter activity is undetectable in the uninduced condition but reaches high
      levels when induced. We used the czcCBA promoter to construct a tightly
      controlled expression vector series, pLY vectors (pLY-A, pLY-B and pLY-C). These
      differed by just one base pair at the multiple cloning sites, allowing convenient
      in-frame cloning of any genes for expression. Using the luxCDABE reporter, this
      expression system was shown to be controlled by Zn in a dose-dependent manner in
      Pseudomonas; cloning the sacB gene encoding levansucrase onto the pLY-C vector
      enabled Zn-controlled growth of P. aeruginosa PAO1. These pLY vectors provide a
      useful tool for functional characterization of genes and controlled production of
      difficult or toxic proteins in Pseudomonas sp.

PMID- 23881320
TI  - Biodegradation of polyvinyl alcohol by a brown-rot fungus, Fomitopsis pinicola.
AB  - A brown-rot fungus, Fomitopsis pinicola, degraded polyvinyl alcohol (PVA) in
      quartz sand but not in liquid culture. From gel permeation chromatography
      analysis, the high-molecular-weight fraction of PVA was decreased by the action
      of F. pinicola but the coloration of the culture filtrate with I2 solution
      increased. The reason for the increase in coloration was assumed to be the
      increase in the low-molecular-weight fraction in degraded PVA. Diffuse
      reflectance infrared Fourier transform spectral analysis showed that spectral
      changes of the fungally degraded PVA were similar to those of PVA treated with
      Fenton's reagent suggesting that PVA degradation by F. pinicola was via the
      Fenton reaction. F. pinicola can thus be used to degrade PVA in woody wastes.

PMID- 23881321
TI  - Differential sensitivities of the growth of Escherichia coli to acrylate under
      aerobic and anaerobic conditions and its effect on product formation.
AB  - The effect of acrylate on the growth of Escherichia coli was determined under
      aerobic and anaerobic conditions in glucose-defined medium. Growth occurred with
      up to 35 mM acrylate under aerobic conditions but ceased at 5 mM acrylate under
      anaerobic conditions. This differential sensitivity can be attributed to
      inhibition of pyruvate formate lyase and/or pflB gene repression, as this enzyme
      is necessary for anaerobic growth of E. coli. The effect of acrylate on end
      product distribution was also determined by growing E. coli first aerobically,
      then switching to anaerobic conditions. In the absence of acrylate, E. coli
      generated the typical distribution of mixed-acid products, with about 12 % of
      pyruvate being metabolically converted to lactate. In contrast, in the presence
      of 5 mM acrylate, E. coli converted 83 % of pyruvate to lactate, consistent with
      a reduction in pyruvate formate lyase activity.

PMID- 23881322
TI  - Autoprocessing: an essential step for expression and purification of enterovirus
      71 3C(pro) in Escherichia coli.
AB  - A gene encoding the 3BC of human enterovirus 71 (EV71) was cloned and inserted
      into a derivative of plasmid pET-32a(+) driven by T7 promoter. The expressed 3C
      protease (3C(pro)) autocatalytically cleaved itself from the recombinant protein
      Trx-3BC and the mature 3C(pro) partitioned in the soluble fraction of bacterial
      lysate. The 13-amino-acid peptide substrates with the junction of 3B/3C were used
      to verify the proteolysis activity of the purified 3C(pro). The EV71 3C(pro) had
      a Km value of 63 MUM (measured by a continuous fluorescence assay). The other
      solid-phase activity assay of the EV71 3C(pro) was developed using HPLC to
      analyze the proteolytic products. The combination of two activity assays
      contributes to promote the identification of the specific inhibitors targeted to
      the EV71 3C(pro).

PMID- 23881323
TI  - A mutation in the Xanthomonas oryzae pv. oryzae wxoD gene affects xanthan
      production and chemotaxis.
AB  - Xanthomonas oryzae pv. oryzae causes bacterial blight in rice (Oryza sativa L.).
      The effect of a mutation in the wxoD gene, that encodes a putative O-antigen
      acetylase, on xanthan production as well as bacterial chemotaxis was
      investigated. The mutation increased xanthan production by 52 %. The mutant
      strain was non-motile on semi-solid agar swarm plates. In addition, several genes
      involved in chemotaxis, including the cheW, cheV, cheR, and cheD genes, were down
      regulated by a mutation in the wxoD gene. Thus, the mutation in the wxoD gene
      affects xanthan production as well as bacterial chemotaxis. However, the wxoD
      gene is not essential for the virulence of X. oryzae.

PMID- 23881324
TI  - A wider role for polyamines in biofilm formation.
AB  - Polyamines play an essential role in biofilm formation of diverse Gram-negative
      and Gram-positive bacteria. Biosynthetic pathways and transport systems for
      diverse polyamines have been identified as key components of bacterial biofilm
      formation. 

PMID- 23881325
TI  - Incubation of sperm heads impairs fertilization and early embryo development
      following intracytoplasmic sperm injection (ICSI) by decreasing oocyte activation
      in mice.
AB  - When intracytoplasmic sperm injection (ICSI) is performed in mice, isolation of
      sperm heads is usually performed prior to injections in order to increase the
      efficiency of the procedure. Consequently, the isolated sperm heads undergo an
      inevitable incubation in vitro. However, little is known about the effects of
      this incubation step on fertilization and embryo development following ICSI. When
      we incubated sperm heads at 37  degrees C, there was a significant time-dependent
      decrease in fertilization and blastocyst formation. Moreover, the DNA integrity
      of the sperm heads was maintained over 12 h incubation. Using assisted oocyte
      activation, these defects in fertilization and embryo development were rescued.
      Taken together, incubation of sperm heads following isolation can affect the
      oocyte-activating capacity of sperm thereby compromising fertilization and embryo
      development associated with ICSI.

PMID- 23881326
TI  - Purification and characterization of two extracellular polyhydroxyalkanoate
      depolymerases from Pseudomonas mendocina.
AB  - Two polyhydroxyalkanoate depolymerases, PHAase I and PHAase II, were purified to
      homogeneity from the culture supernatant of an effective PHA-degrading bacterium,
      Pseudomonas mendocina DS04-T. The molecular masses of PHAase I and PHAase II were
      determined by SDS-PAGE as 59.4 and 33.8 kDa, respectively. Their optimum pH
      values were 8.5 and 8, respectively. Enzymatic activity was optimal at 50 
      degrees C. Both purified enzymes could degrade PHB, PHBV, and P(3HB-co-4HB).
      Addition of Na(+) and K(+) slightly increased the rate of PHAase II. EDTA
      significantly inhibited PHAase II but not PHAase I. Mercaptoethanol and H2O2 also
      inhibited the activities of both enzymes.

PMID- 23881327
TI  - Overexpression of a novel chrysanthemum Cys2/His2-type zinc finger protein gene
      DgZFP3 confers drought tolerance in tobacco.
AB  - A drought stress-responsive Cys2/His2-type zinc finger protein gene DgZFP3 was
      previously isolated (Liu et al., Afr J Biotechnol 11:7781-7788, 2012b) from
      chrysanthemum. To assess roles of DgZFP3 in plant drought stress responses, we
      performed gain-of-function experiment. The DgZFP3-overexpression tobacco plants
      showed significant drought tolerance over the wild type (WT). The transgenic
      lines exhibited less accumulation of H2O2 under drought stress, more accumulation
      of proline and greater activities of peroxidase (POD) and superoxide dismutase
      than the WT under both control conditions and drought stress. In addition, there
      was greater up-regulation of the ROS-related enzyme genes (NtSOD and NtPOD) and
      stress-related genes (NtLEA5 and NtDREB) in transgenic lines under normal or
      drought conditons. Thus DgZFP3 probably plays a positive regulatory role in
      drought stress response and has the potential to be utilized in transgenic
      breeding to improve drought stress tolerance in plants.

PMID- 23881329
TI  - Two-helper-strain co-culture system: a novel method for enhancement of 2-keto-L
      gulonic acid production.
AB  - A novel two-helper-strain co-culture system (TSCS) was developed to enhance 2
      keto-L-gulonic acid (2-KLG) productivity for vitamin C production. Bacillus
      megaterium and B. cereus (with a seeding culture ratio of 1:3, v/v), used as
      helper strains, increased the 2-KLG yield using Ketogulonigenium vulgare compared
      to the conventional one-helper-strain (either B. cereus or B. megaterium) co
      culture system (OSCS). After 45 h cultivation, 2-KLG concentration in the TSCS
      (69 g l(-1)) increased by 8.9 and 7 % over that of the OSCS (B. cereus: 63.4 g l(
      1); B. megaterium: 64.5 g l(-1)). The fermentation period of TSCS was 4 h shorter
      than that of OSCS (B. cereus). The increased cell numbers of K. vulgare
      stimulated by the two helper strains possibly explain the enhanced 2-KLG yield.
      The results imply that TSCS is a viable method for enhancing industrial
      production of 2-KLG.

PMID- 23881328
TI  - Mutant strains of Pichia pastoris with enhanced secretion of recombinant
      proteins.
AB  - Although Pichia pastoris is a popular protein expression system, it exhibits
      limitations in its ability to secrete heterologous proteins. Therefore, a REMI
      (restriction enzyme mediated insertion) strategy was utilized to select mutant
      beta-g alactosidase s upersecretion (bgs) strains that secreted increased levels
      of a beta-galactosidase reporter. Many of the twelve BGS genes may have functions
      in intracellular signaling or vesicle transport. Several of these strains also
      appeared to contain a more permeable cell wall. Preliminary characterization of
      four bgs mutants showed that they differed in the ability to enhance the export
      of other reporter proteins. bgs13, which has a disruption in a gene homologous to
      Saccharomyces cerevisiae protein kinase C (PKC1), gave enhanced secretion of most
      recombinant proteins that were tested, raising the possibility that it has the
      universal super-secreter phenotype needed in an industrial production strain of
      P. pastoris.

PMID- 23881330
TI  - Discovery of a novel esterase subfamily sharing an identified arm sequence
      (ArmEst) by gene-specific metagenomic PCR.
AB  - A gene-specific, metagenomic PCR method has led to the discovery of a novel
      esterase subfamily consisting of five homologous members. Sequence analysis of
      this esterase subfamily, named the ArmEst subfamily, revealed a unique conserved
      pattern with a significant variable interior sequence flanked by two symmetric
      and identical long arm sequences. The two homologous long arm sequences had 100 %
      sequence identity and symmetry at both ends between the five members of this
      esterase class, but only 17-58 % identity was shared for the internal sequence.
      The biochemical properties of two of the ArmEst esterases definitively
      demonstrated that they are true active esterases rather than pseudogenes. This is
      the first report presenting an esterase subfamily containing a unique arm
      sequence, indicating a rare homologous recombination occurring in the coding area
      of a functional gene to generate their functional diversity.

PMID- 23881331
TI  - Sulfotransferase-independent genotoxicity of illudin S and its acylfulvene
      derivatives in bacterial and mammalian cells.
AB  - Acylfulvenes are a class of antitumor agents derived from illudin S, a
      sesquiterpenoid toxin isolated from mushrooms of the genus Omphalotus. Although
      DNA appears to be their major target, no data concerning mutagenicity of
      acylfulvenes are available in the literature, and limited data have been
      published on illudin S. Enzyme-mediated biotransformations have been demonstrated
      to influence the cytotoxicity of acylfulvenes. Illudin S and some acylfulvenes
      [e.g., (-)-6-hydroxymethylacylfulvene (HMAF)] are allylic alcohols with potential
      for enhanced cytotoxicity and genotoxicity by means of metabolic sulfation.
      Therefore, we studied the influence of various heterologously expressed human
      sulfotransferases (SULTs) on biological activities of illudin S and HMAF in
      bacterial and mammalian cells. (-)-Acylfulvene (AF) was tested as a congener
      lacking an allylic hydroxyl group. We found: (1) all three compounds were
      mutagenic in standard Salmonella typhimurium strains TA98, TA100 and TA104; (2)
      they induced gene mutations (at the hypoxanthine phosphoribosyl transferase
      locus) and sister chromatid exchange (SCE) in Chinese hamster V79 cells; (3)
      these effects were practically unaffected when human SULTs were expressed in the
      target bacteria or mammalian cells (using SCE as the endpoint); (4) illudin S
      demonstrated 40-600 times higher genotoxic activities than the semisynthetic
      acylfulvenes studied; it was positive in the SCE test even at a concentration of
      0.3 nM; (5) genotoxicity in mammalian cells was observed at substantially lower
      concentrations of the compounds than required for a positive result in the
      bacterial test (400 nM with illudin S). We conclude that illudin S, HMAF and AF
      are potent genotoxicants and human SULTs do not play a significant role in their
      bioactivation. 

PMID- 23881332
TI  - In vivo influence of sodium fluoride on sperm chemotaxis in male mice.
AB  - Reproductive process covers lots of procedures, including capacitation,
      hyperactivation, chemotaxis and the acrosome reaction. Each plays an important
      role in the success of fertilization. Although multiple studies have reported the
      toxic effects of fluoride on the male reproduction, the effect of fluoride on
      sperm chemotaxis is little known. This study is to examine the effect of fluoride
      on the sperm chemotaxis and then to reveal the underling mechanisms of fluoride
      toxicity in sperm chemotaxis. 260 healthy Kunming male mice (8 weeks old) were
      randomly divided into four groups and exposed to 50, 100, 150 mg NaF/L in the
      drinking water for 8 weeks. At the end of the exposure, sperm chemotaxis was
      examined using a microchannel-based device. Ca(2+) concentration, adenylate
      cyclase (AC) content and mRNA expression of mACIII, mACVIII, Golf alpha,
      CatSper1, CatSper2 were measured to elucidate the possible molecular mechanisms.
      The results showed that the percentage of chemotactic sperm was decreased by NaF
      in a dose-dependent manner. In the 100 and 150 mg/L groups, Ca(2+) concentration
      and AC content were notably lower than the control group. Compared with the
      control group, mRNA expression of CatSper1 in the 100 and 150 mg/L treatment
      groups was decreased significantly, and other genes showed no statistical
      difference. These data suggested that excessive fluoride did adversely affect
      sperm chemotaxis. The alteration of Ca(2+) concentration, AC content and CatSper1
      mRNA expression level may play a key role in the mechanism underlying the
      affection.

PMID- 23881333
TI  - Does upper-body compression improve 3 * 3-min double-poling sprint performance?
AB  - PURPOSE: To evaluate whether upper-body compression affects power output and
      selected metabolic, cardiorespiratory, hemodynamic, and perceptual responses
      during three 3-min sessions of double-poling (DP) sprint. METHOD: Ten well
      trained male athletes (25 +/- 4 y, 180 +/- 4 cm, 74.6 +/- 3.2 kg) performed such
      sprints on a DP ski ergometer with and without a long-sleeved compression
      garment. RESULT: Mean power output was not affected by such compression (216 +/-
      25 W in both cases; P = 1.00, effect size [ES] = 0.00), although blood lactate
      concentration was lowered (P < .05, ES = 0.50-1.02). Blood gases (ES = 0.07
      0.50), oxygen uptake (ES = 0.04-0.28), production of carbon dioxide (ES = 0.01
      0.46), heart rate (ES = 0.00-0.21), stroke volume (ES = 0.33-0.81), and cardiac
      output (ES = 0.20-0.91) were also all unaffected by upper-body compression (best
      P = 1.00). This was also the case for changes in the tissue saturation index (ES
      = 0.45-1.17) and total blood content of hemoglobin (ES = 0.09-0.85), as well as
      ratings of perceived exertion (ES = 0.15-0.88; best P = .96). CONCLUSION: The
      authors conclude that the performance of well-trained athletes during 3 * 3-min
      DP sprints will not be enhanced by upper-body compression.

PMID- 23881334
TI  - Is eccentric exercise an effective treatment for lateral epicondylitis? A
      systematic review.
AB  - OBJECTIVE: To establish the effectiveness of eccentric exercise as a treatment
      intervention for lateral epicondylitis. DATA SOURCES: ProQuest, Medline via
      EBSCO, AMED, Scopus, Web of Science, CINAHL. REVIEW METHODS: A systematic review
      was undertaken to identify randomized and controlled clinical trials
      incorporating eccentric exercise as a treatment for patients diagnosed with
      lateral epicondylitis. Studies were included if: they incorporated eccentric
      exercise, either in isolation or as part of a multimodal treatment protocol; they
      assessed at least one functional or disability outcome measure; and the patients
      had undergone diagnostic testing. The methodological quality of each study was
      assessed using the Modified Cochrane Musculoskeletal Injuries Group score sheet.
      RESULTS: Twelve studies met the inclusion criteria. Three were deemed 'high'
      quality, seven were 'medium' quality, and two were 'low' quality. Eight of the
      studies were randomized trials investigating a total of 334 subjects. Following
      treatment, all groups inclusive of eccentric exercise reported decreased pain and
      improved function and grip strength from baseline. Seven studies reported
      improvements in pain, function, and/or grip strength for therapy treatments
      inclusive of eccentric exercise when compared with those excluding eccentric
      exercise. Only one low-quality study investigated the isolated effects of
      eccentric exercise for treating lateral epicondylitis and found no significant
      improvements in pain when compared with other treatments. CONCLUSION: The
      majority of consistent findings support the inclusion of eccentric exercise as
      part of a multimodal therapy programme for improved outcomes in patients with
      lateral epicondylitis.

PMID- 23881335
TI  - Classification of falls in stroke rehabilitation--not all falls are the same.
AB  - OBJECTIVE: To develop a practical taxonomy of falls and to determine whether
      these different fall groups have different outcomes. DESIGN: Descriptive study
      examining patient characteristics at the time of each fall and iterative
      development of falls taxonomy. SETTING: An inpatient stroke rehabilitation ward.
      METHODS: All falls over 21 months were reviewed retrospectively. Case notes were
      reviewed and each patient's level of functioning at the time of fall, together
      with admission profile and discharge outcomes, were collected. Outcomes for
      fallers (as opposed to falls) were compared using the predominant fall type.
      RESULTS: There were 241 falls in 122 patients and most falls occurred around the
      bed (196 (81%) falls). Toileting-related falls occurred in 54 patients (22.4%).
      The taxonomy proposes seven main fall types. One fall type ('I'm giving it a go')
      appeared quite different and was associated with better functioning at time of
      fall and better outcomes. Other fall types were related to high dependency needs,
      visuospatial difficulties or delirium. Medication-related falls were uncommon in
      this cohort. CONCLUSIONS: The falls taxonomy developed showed four main types of
      falls with different, but overlapping, patient characteristics at time of fall
      with different outcomes. Different fall-prevention strategies may be required for
      each group.

PMID- 23881336
TI  - The use of patient-specific measurement instruments in the process of goal
      setting: a systematic review of available instruments and their feasibility.
AB  - OBJECTIVE: The aim of this study was to identify the currently available patient
      specific measurement instruments used in the process of goal-setting and to
      assess their feasibility. METHODS: After a systematic search in PubMed, EMBASE,
      CINAHL, PsychINFO and REHABDATA, patient-specific instruments were included,
      structured in a goal-setting practice framework and subjected to a qualitative
      thematic analysis of feasibility. RESULTS: A total of 25 patient-specific
      instruments were identified and 11 were included. These instruments can be used
      for goal negotiation, goal-setting and evaluation. Each instrument has its own
      strengths and weaknesses during the different phases of the goal-setting process.
      Objective feasibility data were revealed for all instruments such as
      administration time, instruction, training and availability. Subjective
      feasibility could only be analysed for the Canadian Occupational Performance
      Measure, Goal Attainment Scaling, Self-Identified Goal Assessment and Talking
      Mats. Relevant themes were that Canadian Occupational Performance Measure and
      Goal Attainment Scaling were time consuming and difficult for patients with
      cognitive problems, but they facilitated goal-setting in a client-centred
      approach. Talking Mats was especially feasible for patients with cognitive and
      communication impairments. CONCLUSIONS: A total of 11 instruments were
      identified, and although some had strong points, there is no single good
      instrument that can be recommended specifically. Applying a combination of the
      strengths of the available instruments within a goal-setting framework can
      improve goal setting and tailor it to individual patients.

PMID- 23881337
TI  - An evaluation of treatment integrity in a randomized trial of behavioural therapy
      for low mood in stroke patients with aphasia.
AB  - OBJECTIVE: To assess the treatment integrity of behavioural therapy for low mood
      in stroke patients with aphasia. DESIGN: Participants were recruited to a
      multicentre randomized controlled trial (Communication and Low Mood; CALM trial)
      comparing behavioural therapy with a usual care control group. SUBJECTS: Of the
      51 participants randomly allocated to receive behavioural therapy, 44
      participants completed treatment. METHODS: Participants were assessed on measures
      of disability, language and mood. The number and length of therapy sessions, and
      therapist was recorded. Allocation of time to therapy components was compared
      across three phases of therapy. Associations between levels of disability,
      aphasia, mood and the therapy patients received were determined. Therapy content
      was compared between centres and at the beginning and end of the trial. RESULTS:
      The mean number of therapy sessions was 9.1 (range 3-18, SD 2.6) and the mean
      duration of sessions was 58 minutes (range 30-89 minutes, SD 10.7). Allocation of
      time to each therapy component significantly differed across the three phases of
      therapy (P < 0.05). There were no significant associations (P > 0.05) between the
      length and number of sessions and patients' aphasia, mood or disability,
      suggesting similar levels of therapy were provided regardless of patients'
      characteristics. The content of therapy showed some differences between centres
      (P < 0.01) and there was programme drift in some components of therapy.
      CONCLUSIONS: The results support the ability of the therapists to deliver
      behavioural therapy according to the treatment manual. However there were
      differences between centres and over time in some components of therapy.

PMID- 23881338
TI  - Physical therapist/movement scientist.

PMID- 23881339
TI  - Computational investigation of theoretical models of cleavable and uncleavable
      mucin 1 isoforms.
AB  - Mucin 1 is an important tumor marker, and is notable for the autoproteolytic
      event, a signature of all SEA domain containing proteins. However the isoform
      MUC1/Y, unlike its closest counterpart MUC1/X, is noted to be uncleavable despite
      the presence of the catalytic site. Sequence analysis has revealed the presence
      of an 18 residue segment spliced out from MUC1/Y marking the only difference
      between uncleavable MUC1/Y and cleavable MUC1/X mucin 1 isoforms. This work was
      aimed at studying in silico, the structural and functional significance of the 18
      residue insert in the cleavage process. 3-Dimensional structures of the isoforms
      were predicted using a combined threading and ab initio method followed by
      mutation and normal mode analysis. Our analysis revealed both isoforms to poses
      an intact SEA domain, nevertheless, an altered functional scaffold around the
      cleavage site was noted between the structures. Mutation analysis by alanine
      substitutions at the insert region revealed Ile67 to be more destabilizing,
      resulting in increased fluctuation of the neighboring residues. Predicted
      molecular motions of the protein indicated localized motions in the native,
      rather than the mutated model. Intramolecular interactions between the native and
      I67A structures showed wide variations in main chain and side chain interactions.
      Furthermore, the findings suggest the neighboring residues, in particular Ile67
      contribute more to the structural and functional properties of the protein and
      hence it is predicted to be one of the crucial residues for the cleavable nature
      of MUC1/X. 

PMID- 23881340
TI  - Development and evaluation of new coupling system for lower limb prostheses with
      acoustic alarm system.
AB  - Individuals with lower limb amputation need a secure suspension system for their
      prosthetic devices. A new coupling system was developed that is capable of
      suspending the prosthesis. The system's safety is ensured through an acoustic
      alarm system. This article explains how the system works and provides an in vivo
      evaluation of the device with regard to pistoning during walking. The system was
      designed to be used with silicone liners and is based on the requirements of
      prosthetic suspension systems. Mechanical testing was performed using a universal
      testing machine. The pistoning during walking was measured using a motion
      analysis system. The new coupling device produced significantly less pistoning
      compared to a common suspension system (pin/lock). The safety alarm system would
      buzz if the suspension was going to fail. The new coupling system could securely
      suspend the prostheses in transtibial amputees and produced less vertical
      movement than the pin/lock system. 

PMID- 23881341
TI  - Inadequacies of current approaches to prediabetes and diabetes prevention.
AB  - In view of the global shift from communicable to chronic, non-communicable
      diseases including obesity, prediabetes, and type 2 diabetes mellitus, the
      increasing prevalence of the latter creates a considerable challenge to the
      clinician and public health infrastructure. Despite the substantial research
      efforts in the last 10-15 years highlighting the considerable benefit of
      lifestyle modification in thwarting the insidious progression to diabetes and its
      complications, many individuals will ineluctably progress even when initially
      responsive. Furthermore, the vast majority of individuals with prediabetes remain
      undiagnosed and untreated. Therefore, the responsibilities of the medical and
      public health communities involve identifying new methods for screening and
      identifying those at risk as well as refining therapeutic approaches availing as
      many high-risk individuals as possible to novel treatment modalities.

PMID- 23881342
TI  - Transient pseudo-hypertriglyceridemia: a useful biochemical marker of fructose
      1,6-bisphosphatase deficiency.
AB  - Fructose-1,6-bisphosphatase (FBP) deficiency is an autosomal-recessive disorder
      of gluconeogenesis resulting from mutations within the FBP1 gene. During periods
      of trivial illness, individuals with FBP deficiency may develop ketotic
      hypoglycemia, metabolic acidosis, lactic acidemia, and an increased anion gap.
      Although detection of urinary excretion of glycerol by urine organic acid
      analysis has been previously described, the presence of transient pseudo
      hypertriglyceridemia in serum during metabolic decompensation has not been
      reported before. This study describes four consanguineous Pakistani families, in
      which four patients were diagnosed with FBP deficiency. All showed transient
      pseudo-hypertriglyceridemia during the acute phase of metabolic decompensation,
      which resolved in a metabolically stable phase. Mutations in the FBP1 gene have
      been described from various ethnicities, but there is very limited literature
      available for the Pakistani population. This study also describes one novel
      mutation in the FBP1 gene which seems to be prevalent in Pakistani-Indian
      patients. CONCLUSION: As a result of this study, transient pseudo
      hypertriglyceridemia should be added to glyceroluria, ketotic hypoglycemia,
      metabolic acidosis, and lactic acidosis as a useful biochemical marker of FBP
      deficiency.

PMID- 23881343
TI  - The effect of a weight management program on postural balance in obese children.
AB  - The present study aimed to investigate whether obese children improve their
      balance and postural performance following a 6-month-weight management program.
      Twenty-nine obese children aged 6-14 years were examined posturographically
      before and after participation in weight management program. The interactive
      balance system evaluated the stability index, Fourier spectral analysis, weight
      distribution index, and falling index. The performance was evaluated for eight
      positions requiring closure of eyes, standing on pillows, as well as head turns.
      Anthropometric measurements (e.g., weight, height, BMI, and BMI percentiles) were
      also determined before and after the intervention. We found significant increase
      in height and significant decreased in BMI percentile following the intervention
      program (p<.05). Pre-intervention BMI percentile was found to be correlated with
      stability index in most of the positions measured (e.g., normal open
      position=.464; p=.011). Following the intervention program, an interaction was
      found between BMI percentile differences (pre- versus post-interventional) and
      balance (stability index and F2-F4 frequencies of most standing positions).
      Furthermore, a correlation was found between general stability and the falling
      index (.446; p=.015). Regression analysis showed that only initial weight
      distribution index and post-intervention BMI entered the equation as predictors
      of post-intervention weight distribution index. CONCLUSION: Weight management
      program for childhood obesity improved stability, reduced potential vestibular
      stress/disturbances, and decreased falling probability of the participants.
      Further longitudinal studies are needed to verify the relationship between
      physical activity, weight loss, and reduction of subsequent injuries in obese
      children.

PMID- 23881344
TI  - Odontoid infiltration and spinal compression in Farber Disease: reversal by
      haematopoietic stem cell transplantation.
AB  - Farber disease (FD) is a lysosomal storage disorder caused by accumulation of
      ceramide in various organs and tissues, most notably the central nervous system,
      subcutaneous tissues and respiratory tract. We report a girl who developed major
      destructive bone involvement, which affected the odontoid process and produced
      spinal compression at 9 years of age. Bone involvement was proven histologically
      but resolved, as assessed by serial MRI scanning, following matched unrelated
      donor haematopoietic stem cell transplantation. This transplant resulted in only
      partial donor chimerism (less than 10 % donor cells in peripheral blood), yet
      this was sufficient to almost normalize acid ceramidase levels in leukocytes and
      to produce dramatic improvements in subcutaneous nodules and joint mobility as
      well as the beneficial effect on the involved bone. Unfortunately, the transplant
      was rejected after 2 years but the patient was rescued from an aplastic state by
      successful haploidentical peripheral blood stem cell transplantation and remained
      a full donor chimera without recurrence of the bone involvement and with steadily
      improving mobility at the age of 17 years. We describe an FD patient who
      presented with severe destruction of the odontoid by inflammatory tissue which
      was reversed after long-term control achieved by allogeneic hematopoietic stem
      cell transplantation. After extensive literature search, we believe that this is
      the first report of bony involvement in Farber disease.

PMID- 23881345
TI  - The clinical significance of lymphangiogenesis in renal cell carcinoma.
AB  - BACKGROUND: The formation of lymphatic vessels (lymphangiogenesis) occurs in
      tumor tissues and is crucial for tumor development and progression in some
      cancers. Lymphangiogenesis and its clinical effect on renal cell carcinoma have
      been less thoroughly investigated in comparison with angiogenesis. The aim of
      this study was to evaluate the role of lymphangiogenesis as a prognostic factor
      in renal cell carcinoma (RCC). MATERIAL AND METHODS: The expression of
      peritumoral/intratumoral lymphatics was studied by immunohistochemical methods in
      paraffin-embedded nephrectomy specimens from 133 patients with clear cell
      carcinoma. Patients were divided into 3 groups depending on postoperative follow
      up: I) patients without metastases, II) patients with metastases during follow
      up, and III) patients with metastases during the operation. Peritumoral
      lymphatics (PTL) and intratumoral lymphatics (ITL) were immunostained with a D2
      40 antibody. RESULTS: The mean number of PTL present in each group was I=14.1,
      II=10.6, III=12.1. The mean number of ITL present in each group was I=0.7,
      II=2.3, III=2.3. The 3 groups showed statistically significant differences only
      in the case of ITL. A mean count of ITL >=1 is significantly associated with an
      increased risk of regional lymph node involvement and distant metastasis.
      Patients with expression ITL >0.2 and PTL <=15.2 had a significantly shorter
      cancer-specific survival. CONCLUSIONS: The number of ITL showed an association
      with more aggressive cases of RCC and progression of disease. Therefore, the
      level of expression ITL, together with stage and histological grading, may
      provide valuable predictive information about the outcome of treatment.

PMID- 23881346
TI  - Effect of consecutive intragastric balloon (BIB(r)) plus diet versus single
      BIB(r) plus diet on eating disorders not otherwise specified (EDNOS) in obese
      patients.
AB  - BACKGROUND: Eating disorders are a group of conditions characterised by abnormal
      eating habits. Greater than 50 % of patients with eating disorders have an
      'eating disorder not otherwise specified' (EDNOS). No specific tools exist to
      evaluate EDNOS, and patients are identified only with a diagnosis of exclusion
      from the other eating disorders. The BioEnterics(r) Intragastric Balloon (BIB(r))
      is used worldwide as a short-term treatment option in obese patients. A new
      frequency score was used to evaluate the influence of double consecutive BIB(r)
      treatment compared with single BIB(r) treatment followed by diet on four
      categories of EDNOS (grazing, emotional eating, sweet-eating and after-dinner
      grazing). METHODS: A prospective study allocated 50 obese patients (age range 25
      35, BMI range 40.0-44.9) into two groups: BIB(r) (6 months) followed by diet
      therapy (7 months; group A (N = 25)) and BIB(r) placement for 6 months followed
      by another BIB(r) for 6 months, with a 1-month interval between placement (group
      B (N = 25)). Baseline demographics were similar across both groups. RESULTS: At
      the time of removal of the first BIB(r) device, EDNOS scores in both groups were
      not significantly different, but decreased significantly from baseline. By the
      end of the study, all EDNOS scores were significantly lower in patients
      undergoing consecutive BIB(r), compared with single BIB(r) followed by diet
      therapy. CONCLUSIONS: The placement of an intragastric balloon in obese patients
      allows for a reduction in the intensity of grazing, emotional eating, sweet
      eating and after-dinner grazing. A more significant reduction in the EDNOS score
      was observed with two consecutive BIBs(r).

PMID- 23881347
TI  - Pharmacist-led medication reconciliation to reduce discrepancies in transitions
      of care in Spain.
AB  - BACKGROUND: Medication errors are one of the main causes of morbidity amongst
      hospital inpatients. More than half of medication errors occur at 'interfaces of
      care', when patients are discharged or transferred to the care of another
      physician. Medication reconciliation is the process of reviewing patients'
      complete previous medication regimen, comparing it with current prescriptions,
      and analysing and resolving any discrepancies that the pharmacist does not
      believe to be intentional (unjustified discrepancies). OBJECTIVE: To quantify and
      analyse reconciliation unjustified discrepancies detected by a pharmacist in
      patients admitted to an internal medicine unit (IMU) over a 3-year period.
      SETTING AND METHOD: The hospital employs a pharmacist who acts as a link between
      the primary care services and the internal medicine specialist care unit. A
      retrospective descriptive study on the reconciliation discrepancies found was
      carried out. Medication reconciliation was performed upon admission in all
      patients transferred from the Accident and Emergency department (A&E) and
      admitted to the IMU, and also at the time of discharge. The interventions were
      categorised based on the consensus document on terminology and medication
      classification published by the Spanish Society of Hospital Pharmacy. MAIN
      OUTCOME MEASURE: Number of patients with unjustified discrepancies, also known as
      reconciliation errors. RESULTS: 2,473 patients had their treatment reviewed at
      the time of admission and 1,150 at discharge. 866 reconciliation discrepancies
      were detected in 446 patients (1.94 per patient). 807 (93 %) were accepted by the
      prescribing physician and classified as reconciliation errors. 16.8 % of patients
      had at least one reconciliation error: 63.8 % of these errors were incomplete
      prescriptions, 16.6 % were medication omissions and 10.5 % were errors in dosage,
      administration method and/or frequency. CONCLUSION: The rate of medication errors
      found in this study is low compared with other similar studies. The most common
      error was "incomplete prescriptions", most of them generated by the Accident and
      Emergency department. A computerised clinical history would help to decrease the
      number of reconciliation errors. Pharmacist interventions focused on medication
      reconciliation are well accepted by physicians, improving the quality of clinical
      histories and decreasing the number of medication errors that occur across
      transitions in patient care.

PMID- 23881348
TI  - Breast disease in the pregnant and lactating patient: radiological-pathological
      correlation.
AB  - OBJECTIVE: Substantial physiological changes occur during pregnancy and
      lactation, making breast evaluation challenging in these patients. This article
      reviews the imaging challenges of the breast during pregnancy and lactation. The
      normal imaging appearance, imaging protocols and the imaging features of each
      commonly encountered benign and malignant entity with pathological correlation
      and supporting examples is described. An awareness of the imaging features of the
      breast during these physiological states and of various benign and malignant
      diseases that occur permits optimal management. CONCLUSIONS: Evaluation of the
      pregnant and lactating patients who present with a breast problem is challenging.
      Although ultrasound may characterise the finding in many cases, mammography and
      even MRI may have a role in the management of these patients. TEACHING POINTS: *
      To review physiological changes of the breast during pregnancy and lactation * To
      review imaging protocols of the breast during pregnancy and lactation * Discuss
      imaging findings with pathological correlation of benign and malignant diseases
      in pregnancy and lactation * Discuss pathological correlation of imaging findings
      in pregnancy and lactation.

PMID- 23881349
TI  - A radiological classification system for talocalcaneal coalition based on a multi
      planar imaging study using CT and MRI.
AB  - OBJECTIVE: To develop a radiological classification system for talocalcaneal
      coalition suitable for adults. METHODS AND MATERIALS: A retrospective review was
      performed on patients diagnosed with talocalcaneal coalition from July 2001 to
      November 2011. Based on the cartilaginous or bony nature, facet joint orientation
      and bony structure morphology, we classified talocalcaneal coalitions into four
      types: I (linear with or without posterior hooking), II (talar overgrowth), III
      (calcaneal overgrowth) and IV (complete osseous). RESULTS: Seventy feet (59
      patients) with talocalcaneal coalition were evaluated by CT (61/70 feet) using
      multi-planar reformation and/or magnetic resonance imaging (43/70 feet). Type I,
      II, III and IV coalitions were detected in 45 (64 %), 10 (14 %), 13 (19 %), and 2
      feet (3 %), respectively. Fracture fragments were observed in 16 feet (seven Type
      I and nine Type III coalitions) with hooked or overgrown calcanei and in one foot
      in the talus (Type I). Eleven patients had bilateral talocalcaneal coalitions;
      ten patients had coalitions of the same type and one had both Type I and Type III
      coalitions. Among 48 patients with unilateral involvement, the left and right
      feet were affected in 26 and 22 patients, respectively. CONCLUSIONS: A
      classification system for talocalcaneal coalition based on multi-planar imaging
      studies was developed. KEY POINTS: * A classification system for talocalcaneal
      coalition based on multi-planar imaging was developed. * The relative frequencies
      of different talocalcaneal coalition types were determined. * Fracture fragments
      were easily distinguished and frequently originated from the calcaneus. *
      Fracture fragments were mostly associated with Type I (linear) with posterior
      hooking and Type III (calcaneal overgrowth).

PMID- 23881350
TI  - Synthesis and characterization of Co(III) amidoamine complexes: influence of
      substituents of the ligand on catalytic cyclic carbonate synthesis from epoxide
      and carbon dioxide.
AB  - A series of amidoamine ligands (1) and their cobalt(III) complexes (2) were
      synthesized and characterized by various spectroscopic techniques including (1)H
      NMR and X-ray crystallographic techniques. X-ray crystallography shows that one
      of the complexes, 2a, forms a chiral coordination polymer due to bridge formation
      with Li(+) associated with the complex, although the ligand is achiral. Complex 2
      was employed for catalytic synthesis of cyclic carbonates from epoxides and
      carbon dioxide (CO2) in a solvent free condition. A strong influence of the
      substituents on the ligand 1 was revealed by the varied activity of complex 2.
      The presence of electron withdrawing groups such as chloro (2b) and nitro (2c)
      increases the Lewis acidity of the catalyst, which, in turn, enhances the
      catalytic activity of 2. An electron withdrawing group containing complexes (2b
      and 2c) showed exceptionally high catalytic activity with a turnover frequency
      (TOF) of 662 and 602 h(-1) respectively at 130  degrees C and 300 psig CO2
      pressure. On the other hand, our studies indicate that a catalyst with an
      electron releasing group (2d) showed relatively lower activity with a TOF of 488
      h(-1) under similar reaction conditions. Our results show that cobalt(iii)
      complexes follow the reactivity order of 2d < 2a < 2c < 2b.

PMID- 23881351
TI  - Gender differences in bladder control: from babies to elderly.
AB  - In both sexes, there are anatomical and behavioral differences in dealing with
      bladder control, as well as voiding and incontinence. Despite intensive research
      within the last decades, the differences in physiology and pathophysiology as
      well as gender differences of bladder control and continence are still poorly
      understood and further research is highly needed. In babies, gender difference
      seems to be most likely caused by a difference in maturity rate of the bladder.
      After gaining bladder control, behavior starts to be influenced by socialization.
      During preschool and school, children experience a negative perception of school
      toilets. Especially girls crouch over the toilet seat and train to empty the
      bladder without relaxation of the pelvic floor. This posture may lead to bladder
      dysfunction. Often adult women continue this bad habit and bladder dysfunction
      may consolidate. From the fourth decade in both sexes lower urinary tract
      symptoms start to develop. However, men and women handle the problem variedly
      showing gender differences in coping strategies with better coping mechanisms in
      women. In general, gender difference in help seeking and receiving treatment
      increases with younger age. In elderly, urinary incontinence is only associated
      with a higher mortality in men, and elderly men seek more often professional
      help. Aim of the review is to provide an insight into gender differences of
      bladder control and bladder dysfunction.

PMID- 23881352
TI  - Oncologic outcomes after minimally invasive radical prostatectomy in patients
      with seminal vesicle invasion (pT3b) without adjuvant therapy.
AB  - PURPOSE: To evaluate the long-term outcomes of patients with prostate cancer who
      have pathological pT3b N0-Nx, with postoperative PSA < 0.1 ng/ml and no
      systematic adjuvant treatment. MATERIALS AND METHODS: Using a monocentric
      prospectively maintained database, we identified among 2,142 men who underwent
      minimally invasive radical prostatectomy, 104 pT3b N0-Nx patients, with
      postoperative PSA < 0.1 ng/ml and at least 5 years of follow-up. Patients were
      considered for salvage treatment at biochemical recurrence (PSA >= 0.2 ng/ml).
      RESULTS: The median time of follow-up was 83.5 months (interquartile range [IQR]:
      69-99). Overall, 102 patients (98 %) had T2 clinical stage or less. Specimen
      Gleason score was 7 in 71 patients (68 %) and <7 in 15 (14 %). Thirty-eight
      patients (37 %) were upgraded for Gleason score after radical prostatectomy. The
      overall 5-year probability of freedom from biochemical recurrence for the entire
      cohort was 55.8 % (95 % CI 45.8-65.8) and 73.3 % for patients who had specimen
      Gleason score <7 (p = 0.005). In univariate analysis, specimen Gleason score and
      surgical margin status were significant predictors for biochemical failure after
      radical prostatectomy (p = 0.05 and 0.007, respectively). In multivariate
      analysis, only specimen Gleason score >7 was significantly associated with
      biochemical failure (p = 0.009). CONCLUSION: SVI is an adverse prognostic factor,
      but it is not associated with a uniformly poor prognosis. Specimen Gleason score
      and surgical margin status are significant predictors of recurrence after radical
      prostatectomy in patients with prostate cancer and SVI.

PMID- 23881353
TI  - Measurement of pneumococcal polysaccharide vaccine responses for immunodeficiency
      diagnostics: combined IgG responses compared to serotype specific IgG responses.

PMID- 23881355
TI  - New concepts in diagnostics for infectious diarrhea.
AB  - Conventional approaches to the diagnosis of infectious diarrhea must include
      several modalities to detect an array of potential viruses, bacteria, and
      parasites. We will provide a general overview of the wide range of diagnostic
      modalities available for enteropathogens, briefly discuss some of the limitations
      of conventional methods, and then focus on new molecular methods, including real
      time PCR and next-generation sequencing. In particular, we will discuss
      quantitation of pathogen load with these techniques. We will then describe
      examples whereby novel diagnostics may help illuminate the etiology of infectious
      diarrhea, where they may not, and how they may benefit studies of immunity to
      enteric infections.

PMID- 23881354
TI  - Central cholinergic activation of a vagus nerve-to-spleen circuit alleviates
      experimental colitis.
AB  - The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based
      mechanism that regulates immune responses and cytokine production through alpha7
      nicotinic acetylcholine receptor (alpha7nAChR) signaling. Decreased efferent
      vagus nerve activity is observed in inflammatory bowel disease. We determined
      whether central activation of this pathway alters inflammation in mice with
      colitis and the mediating role of a vagus nerve-to-spleen circuit and alpha7nAChR
      signaling. Two experimental models of colitis were used in C57BL/6 mice. Central
      cholinergic activation induced by the acetylcholinesterase inhibitor galantamine
      or a muscarinic acetylcholine receptor agonist treatments resulted in reduced
      mucosal inflammation associated with decreased major histocompatibility complex
      II level and pro-inflammatory cytokine secretion by splenic CD11c+ cells mediated
      by alpha7nAChR signaling. The cholinergic anti-inflammatory efficacy was
      abolished in mice with vagotomy, splenic neurectomy, or splenectomy. In
      conclusion, central cholinergic activation of a vagus nerve-to-spleen circuit
      controls intestinal inflammation and this regulation can be explored to develop
      novel therapeutic strategies.

PMID- 23881357
TI  - Dysembryoplastic neuroepithelial tumor with rapid recurrence of pilocytic
      astrocytoma component.
AB  - Dysembryoplastic neuroepithelial tumor (DNT) rarely has aggressive behavior with
      recurrence. The authors describe a case of DNT with rapid re-growth and features
      of pilocytic astrocytoma. A 19-year-old girl presented with a 3-year history of
      complex partial seizure, which was presumably because of DNT located in the left
      parietal lobe. The tumor was resected, although a tiny residual lesion with
      cystic space enlarged with ring enhancement identified on MRI 14 days after
      surgery resulted in re-excision. The recurrent tumor was eventually proved to be
      predominantly composed of pilocytic astrocytoma. DNT is known to recur only
      rarely as a tumor with morphologically different components, and no cases of
      recurrent DNT with rapidly-growing pilocytic astrocytoma have hitherto been
      reported in the literature. This phenomenon may be histological "replacement" at
      recurrence.

PMID- 23881356
TI  - Polyreactive antibodies plus complement enhance the phagocytosis of cells made
      apoptotic by UV-light or HIV.
AB  - Polyreactive antibodies are a major component of the natural antibody repertoire
      and are capable of binding a variety of structurally unrelated antigens. Many of
      the properties attributed to natural antibodies, in fact, are turning out to be
      due to polyreactive antibodies. In humans, each day, billions of cells undergo
      apoptosis. In the present experiments, we show by ImageStream technology that
      although polyreactive antibodies do not bind to live T cells they bind to both
      the plasma membrane and cytoplasm of late apoptotic cells, fix complement,
      generate the anaphylatoxin C5a and increase by as much as 5 fold complement
      mediated phagocytosis by macrophages. Of particular importance, T cells
      undergoing apoptosis following infection with HIV also bind polyreactive
      antibodies and are phagocytosed. We conclude that the polyreactive antibodies in
      the natural antibody repertoire contribute in a major way to the clearance of
      cells made apoptotic by a variety of natural and infectious processes. 

PMID- 23881358
TI  - Tolerance to cadmium in plants: the special case of hyperaccumulators.
AB  - On sols highly polluted by trace metallic elements the majority of plant species
      are excluders, limiting the entry and the root to shoot translocation of trace
      metals. However a rare class of plants called hyperaccumulators possess
      remarkable adaptation because those plants combine extremely high tolerance
      degrees and foliar accumulation of trace elements. Hyperaccumulators have
      recently gained considerable interest, because of their potential use in
      phytoremediation, phytomining and biofortification. On a more fundamental point
      of view hyperaccumulators of trace metals are case studies to understand metal
      homeostasis and detoxification mechanisms. Hyperaccumulation of trace metals
      usually depends on the enhancement of at least four processes, which are the
      absorption from the soil, the loading in the xylem in the roots and the unloading
      from the xylem in the leaves and the detoxification in the shoot. Cadmium is one
      of the most toxic trace metallic elements for living organisms and its
      accumulation in the environment is recognized as a worldwide concern. To date,
      only nine species have been recognized as Cd hyperaccumulators that is to say
      able to tolerate and accumulate more than 0.01 % Cd in shoot dry biomass. Among
      these species, four belong to the Brassicaceae family with Arabidopsis halleri
      and Noccaea caerulescens being considered as models. An update of our knowledge
      on the evolution of hyperaccumulators will be presented here. 

PMID- 23881359
TI  - Study on the interaction between a water-soluble dinuclear nickel complex and
      bovine serum albumin by spectroscopic techniques.
AB  - The interaction of a water-soluble dinuclear nickel(II) complex,
      [Ni2(EGTB)(CH3CN)4](ClO4)4.4H2O (EGTB = ethylene glycol-bis(beta-aminoethyl
      ether) N,N,N',N'-tetrakis(2-benzimidazoyl)) (1), and bovine serum albumin (BSA)
      was investigated under physiological conditions using fluorescence, synchronous
      fluorescence, UV-vis absorption and circular dichroism (CD). The experimental
      results suggested that the nickel(II) complex could bind to BSA with binding
      constant (K) ~ 10(4) M(-1) and quench the intrinsic fluorescence of BSA through a
      static quenching mechanism. The thermodynamic parameters, DeltaG degrees , DeltaH
      degrees , and DeltaS degrees , calculated at different temperatures, indicated
      that the binding reaction was spontaneous and electrostatic interactions played a
      major role in this association. Based on the number of binding sites, it was
      considered that one molecule of complex 1 could bind to a single site or two
      sites of the BSA molecule or the two binding modes coexisted. In view of the
      results of site marker competition experiments, the reactive sites of BSA to
      complex 1 mainly located in subdomain IIA (site I) and subdomain IIIA (site II)
      of BSA. Moreover, the binding distance, r, between donor (BSA) and acceptor
      (complex 1) was 5.13 nm according to Forster nonradiation energy transfer theory.
      Finally, as shown by the UV-vis absorption, synchronous fluorescence and CD,
      complex 1 could induce conformation and microenvironmental changes of BSA. The
      results obtained herein will be of biological significance in toxicology
      investigation and anticancer metallodrug design.

PMID- 23881361
TI  - Overexpression of a pea DNA helicase (PDH45) in peanut (Arachis hypogaea L.)
      confers improvement of cellular level tolerance and productivity under drought
      stress.
AB  - Peanut, a major edible oil seed crop globally is predominantly grown under
      rainfed conditions and suffers yield losses due to drought. Development of
      drought-tolerant varieties through transgenic technology is a valid approach.
      Besides superior water relation traits like water mining, intrinsic cellular
      level tolerance mechanisms are important to sustain the growth under stress. To
      achieve this objective, the focus of this study was to pyramid drought adaptive
      traits by overexpressing a stress responsive helicase, PDH45 in the background of
      a genotype with superior water relations. PCR, Southern, and RT-PCR analyses
      confirmed stable integration and expression of the PDH45 gene in peanut
      transgenics. At the end of T3 generation, eight transgenic events were identified
      as promising based on stress tolerance and improvement in productivity. Several
      transgenic lines showed stay-green phenotype and increased chlorophyll stability
      under stress and reduced chlorophyll retardation under etherel-induced simulated
      stress conditions. Stress-induced root growth was also substantially higher in
      the case of transformants. This was reflected in increased WUE (low Delta13C) and
      improved growth rates and productivity. The transgenics showed 17.2 and 26.75 %
      increase in yield under non-stress and stress conditions over wild type
      ascertaining the feasibility of trait pyramiding strategy for the development of
      drought-tolerant peanut.

PMID- 23881362
TI  - Positional differences in match running performance and physical collisions in
      men rugby sevens.
AB  - PURPOSE: This study describes the physical match demands relative to positional
      group in male rugby sevens. METHODS: Ten highly trained players were investigated
      during competitive matches (N = 23) using GPS technology, heart rate (HR), and
      video recording. RESULTS: The relative distance covered by the players throughout
      the match was 102.3 +/- 9.8 m/min. As a percentage of total distance, 35.8% (36.6
      +/- 5.9 m/min) was covered walking, 26.0% (26.6 +/- 5.5 m/min) jogging, 10.0%
      (10.2 +/- 2.4 m/min) running at low intensity, 14.2% (14.5 +/- 4.0 m/min) at
      medium intensity, 4.6% (4.7 +/- 1.6 m/min) at high intensity, and 9.5% (9.7 +/-
      3.7 m/min) sprinting. For the backs, a substantial decrease in total distance and
      distance covered at low, medium, and high intensity was observed in the second
      half. Forwards exhibited a substantial decrease in the distance covered at medium
      intensity, high intensity, and sprinting in the 2nd half. Backs covered
      substantially more total distance at medium and sprinting speeds than forwards.
      In addition, the maximum length of sprint runs was substantially greater for the
      backs than forwards. On the contrary, forwards performed more tackles. The mean
      HR during the match in backs and forwards was similar, with the exception of time
      spent at HR intensities >90%HRmax, which was substantially higher in forwards.
      CONCLUSION: These findings provide a description of the different physical
      demands placed on rugby sevens backs and forwards. This information may be
      helpful in the development of positional and/or individualized physical-fitness
      training programs.

PMID- 23881363
TI  - [Strategies to ensure careers of young academics in plastic surgery - analysis of
      the current situation and future perspectives].
AB  - Recruitment problems in surgical disciplines have become an increasingly debated
      topic. On the one hand current career prospects appear to be less attractive than
      those were seen for the previous generation. On the other hand the demands for a
      so-called "work-life balance" have changed and the proportion of female students
      and colleagues in medicine has risen and will continue to increase. Although
      Plastic Surgery currently seems to be less affected by these problems than other
      surgical disciplines, securing a qualified supply of young academics in Plastic
      Surgery is a prerequisite for the further development of this discipline. The
      traditional model of mentoring is discussed and the role of coaching in a sense
      of helping the mentorees examine what they are doing in the light of their
      intentions and goals is reflected. The present article tries to analyze the
      current status of academic Plastic Surgery from the viewpoint of German
      university senior surgeons in academic plastic surgery, and aims to highlight the
      specific prospects for young academics against the backdrop of an often one-sided
      and superficial perception of this profession.

PMID- 23881364
TI  - Aptamer-based label-free detection of PDGF using ruthenium(II) complex as
      luminescent probe.
AB  - We report a simple, cost-effective, and label-free detection method, consisting
      of a platelet-derived growth factor (PDGF) binding aptamer and hydrophobic Ru(II)
      complex as a sensor system for PDGF. The binding of PDGF with the aptamer results
      in the weakening of the aptamer-Ru(II) complex, monitored by luminescence signal.
      A substantial enhancement in the luminescence intensity of Ru(II) complex is
      observed in the presence of aptamer due to the hydrophobic interaction. Upon
      addition of PDGF, the luminescence intensity is decreased, due to the stronger
      interaction between the aptamer and PDGF resulting in the displacement of Ru(II)
      complex to the aqueous solution. Our assay can detect a target specifically in a
      complex medium such as the mixture of proteins, at a concentration of 0.8 pM. 

PMID- 23881360
TI  - Role of RNA structure motifs in IRES-dependent translation initiation of the
      coxsackievirus B3: new insights for developing live-attenuated strains for
      vaccines and gene therapy.
AB  - Internal ribosome entry site (IRES) elements are highly structured RNA sequences
      that function to recruit ribosomes for the initiation of translation. In contrast
      to the canonical cap-binding, the mechanism of IRES-mediated translation
      initiation is still poorly understood. Translation initiation of the
      coxsackievirus B3 (CVB3), a causative agent of viral myocarditis, has been shown
      to be mediated by a highly ordered structure of the 5' untranslated region
      (5'UTR), which harbors an IRES. Taking into account that efficient initiation of
      mRNA translation depends on temporally and spatially orchestrated sequence of RNA
      protein and RNA-RNA interactions, and that, at present, little is known about
      these interactions, we aimed to describe recent advances in our understanding of
      molecular structures and biochemical functions of the translation initiation
      process. Thus, this review will explore the IRES elements as important RNA
      structures and the significance of these structures in providing an alternative
      mechanism of translation initiation of the CVB3 RNA. Since translation initiation
      is the first intracellular step during the CVB3 infection cycle, the IRES region
      provides an ideal target for antiviral therapies. Interestingly, the 5' and
      3'UTRs represent promising candidates for the study of CVB3 cardiovirulence and
      provide new insights for developing live-attenuated vaccines.

PMID- 23881365
TI  - Identification of urinary metabolites of imperatorin with a single run on an
      LC/Triple TOF system based on multiple mass defect filter data acquisition and
      multiple data mining techniques.
AB  - The detection of drug metabolites, especially for minor metabolites, continues to
      be a challenge because of the complexity of biological samples. Imperatorin (IMP)
      is an active natural furocoumarin component originating from many traditional
      Chinese herbal medicines and is expected to be pursued as a new vasorelaxant
      agent. In the present study, a generic and efficient approach was developed for
      the in vivo screening and identification of IMP metabolites using liquid
      chromatography-Triple TOF mass spectrometry. In this approach, a novel on-line
      data acquisition method mutiple mass defect filter (MMDF) combined with dynamic
      background subtraction was developed to trace all probable urinary metabolites of
      IMP. Comparing with the traditionally intensity-dependent data acquisition
      method, MMDF method could give the information of low-level metabolites masked by
      background noise and endogenous components. Thus, the minor metabolites in
      complex biological matrices could be detected. Then, the sensitive and specific
      multiple data-mining techniques extracted ion chromatography, mass defect filter,
      product ion filter, and neutral loss filter were used for the discovery of IMP
      metabolites. Based on the proposed strategy, 44 phase I and 7 phase II
      metabolites were identified in rat urine after oral administration of IMP. The
      results indicated that oxidization was the main metabolic pathway and that
      different oxidized substituent positions had a significant influence on the
      fragmentation of the metabolites. Two types of characteristic ions at m/z 203 and
      219 can be observed in the MS/MS spectra. This is the first study of IMP
      metabolism in vivo. The interpretation of the MS/MS spectra of these metabolites
      and the proposed metabolite pathway provide essential data for further
      pharmacological studies of other linear-type furocoumarins. 

PMID- 23881366
TI  - Novel sheathless CE-MS interface as an original and powerful infusion platform
      for nanoESI study: from intact proteins to high molecular mass noncovalent
      complexes.
AB  - Development of nano-electrospray (nanoESI) sources allowed to increase
      significantly the sensitivity which is often lacking when studying biological
      noncovalent assemblies. However, the flow rate used to infuse the sample into the
      mass spectrometer cannot be precisely controlled with nanoESI and the robustness
      of the system could represent an issue. In this study, we have used a sheathless
      capillary electrophoresis-mass spectrometry (CESI) prototype as a nanoESI
      infusion device. The hydrodynamic mobilization of the capillary content was
      characterized and the ability of the system to generate a stable electrospray
      under controlled flow rate conditions ranging from 4 up to 900 nL/min was
      demonstrated. The effect of the infusing flow rate on the detection of an intact
      model protein analyzed under native conditions was investigated. Results
      demonstrated a significant increase in sensitivity of 46-fold and a signal-to
      noise ratio improvement of nearly 5-fold when using an infusing flow rate from
      456.9 down to 13.7 nL/min. The CESI prototype was further used to detect
      successfully the beta ring homodimer in its native conformation. Obtained results
      were compared with those achieved with conventional ESI. Intensity signals were
      increased by a factor of 5, while sample consumption decreased 80 times. beta
      ring complexed with the P14 peptide was also studied. Finally, the CESI interface
      was used to observe the quaternary structure of native hemocyanins from Carcinus
      maenas crabs; this high molecular complex coexisting under various degrees of
      complexation and resulting in masses ranging from 445 kDa to 1.34 MDa.

PMID- 23881367
TI  - Testing the incremental predictive accuracy of new markers.
AB  - BACKGROUND: It has become commonplace to use receiver operating curve (ROC)
      methodology to evaluate the incremental predictive accuracy of new markers in the
      presence of existing predictors. However, concerns have been raised about the
      validity of this practice. We have evaluated this issue in detail. RESULTS:
      Simulations have been used that show clearly that use of risk predictors from
      nested models as data in subsequent tests comparing areas under the ROC curves of
      the models leads to grossly invalid inferences. Careful examination of the issue
      reveals two major problems: (1) the data elements are strongly correlated from
      case to case and (2) the model that includes the additional marker has a tendency
      to interpret predictive contributions as positive information regardless of
      whether observed effect of the marker is negative or positive. Both of these
      phenomena lead to profound bias in the test. CONCLUSIONS: We recommend strongly
      against the use of ROC methods derived from risk predictors from nested
      regression models to test the incremental information of a new marker.

PMID- 23881368
TI  - Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic
      cell-specific MHC class II expression.
AB  - The enteric pathogen Citrobacter rodentium induces a mucosal IL-17 response in
      CD4(+) T helper (Th17) cells that is dependent on the Nod-like receptors Nod1 and
      Nod2. Here, we sought to determine whether this early Th17 response required
      antigen presentation by major histocompatibility complex class II (MHCII) for
      full induction. At early phases of C. rodentium infection, we observed that the
      intestinal mucosal Th17 response was fully blunted in irradiated mice
      reconstituted with MHCII-deficient (MHCII(-/-) ->WT) hematopoietic cells.
      Surprisingly, we also observed a substantial increase in the relative frequency
      of IL-17(+) CD8(+) CD4(-) TCR-beta(+) cells (Tc17 cells) and FOXP3(+) CD8(+) CD4(
      ) TCR-beta(+) cells in the lamina propria and intraepithelial lymphocyte
      compartment of MHCII(-/-) ->WT mice compared with that in WT->WT counterparts.
      Moreover, MHCII(-/-) ->WT mice displayed increased susceptibility, increased
      bacterial translocation to deeper organs, and more severe colonic histopathology
      after infection with C. rodentium. Finally, a similar phenotype was observed in
      mice deficient for CIITA, a transcriptional regulator of MHCII expression.
      Together, these results indicate that MHCII is required to mount early mucosal
      Th17 responses to an enteric pathogen, and that MHCII regulates the induction of
      atypical CD8(+) T-cell subsets, such as Tc17 cells and FOXP3(+) CD8(+) cells, in
      vivo. 

PMID- 23881369
TI  - It's not just another room...

PMID- 23881370
TI  - Should "normal" saline be our usual choice in normal surgical patients?

PMID- 23881371
TI  - Perioperative management of pacemakers and implantable cardioverter
      defibrillators: it's not just about the magnet.

PMID- 23881372
TI  - Alea iacta est: a new approach to cardiac output monitoring?

PMID- 23881373
TI  - Reasoning of an anomaly: residual block after sugammadex.

PMID- 23881374
TI  - Compounded steroids for epidural injections: what are the issues?

PMID- 23881375
TI  - Safety of modern starches used during surgery: misleading conclusions.

PMID- 23881376
TI  - Safety of HES 130/0.4 not yet settled.

PMID- 23881377
TI  - The role of the beta-adrenergic receptors in cerebral vasodilation during
      hemodilution.

PMID- 23881378
TI  - Teaching neuraxial analgesia: identification of loss of resistance (epidural) and
      intrathecal (spinal) placement of needles--avoid "making a lemon" of yourself.

PMID- 23881379
TI  - Did you know this about your lead apron?

PMID- 23881380
TI  - Propofol effect-site concentrations: hunt the k(e0).

PMID- 23881381
TI  - Dietary intake and food sources of EPA, DPA and DHA in Australian children.
AB  - Secondary analysis of the 2007 Australian National Children's Nutrition and
      Physical Activity survey was undertaken to assess the intake and food sources of
      EPA, DPA and DHA (excluding supplements) in 4,487 children aged 2-16 years. An
      average of two 24-h dietary recalls was analysed for each child and food sources
      of EPA, DPA and DHA were assessed using the Australian nutrient composition
      database called AUSNUT 2007. Median (inter quartile range, IQR) for EPA, DPA and
      DHA intakes (mg/day) for 2-3, 4-8, 9-13, 14-16 year were: EPA 5.3 (1.5-14), 6.7
      (1.8-18), 8.7 (2.6-23), 9.8 (2.7-28) respectively; DPA 6.2 (2.2-14), 8.2 (3.3
      18), 10.8 (4.3-24), 12.2 (5-29) respectively; and DHA 3.9 (0.6-24), 5.1 (0.9-26),
      6.8 (1.1-27), 7.8 (1.5-33) respectively. Energy-adjusted intakes of EPA, DPA and
      DHA in children who ate fish were 7.5, 2 and 16-fold higher, respectively (P <
      0.001) compared to those who did not eat fish during the 2 days of the survey.
      Intake of total long chain n-3 PUFA was compared to the energy adjusted suggested
      dietary target (SDT) for Australian children and 20 % of children who ate fish
      during the 2 days of the survey met the SDT. Fish and seafood products were the
      largest contributors to DHA (76 %) and EPA (59 %) intake, while meat, poultry and
      game contributed to 56 % DPA. Meat consumption was 8.5 times greater than that
      for fish/seafood. Australian children do not consume the recommended amounts of
      long chain omega-3 fatty acids, especially DHA, which could be explained by low
      fish consumption. 

PMID- 23881382
TI  - Aberrant sphingolipid metabolism in the human fallopian tube with ectopic
      pregnancy.
AB  - Sphingosine 1-phosphate (S1P), a product of sphingomyelin metabolism, is
      generated via phosphorylation of sphingosine by sphingosine kinases (SphK). It
      acts via a family of G protein-coupled receptors or as an intracellular second
      messenger for agonists acting through the S1P receptors (S1P1-5). In our study,
      the expression of SphK1 and S1P1 was identified by immunohistochemistry and
      immunoblot. The concentration of S1P was measured using ELISA. The spontaneous
      contraction of isolated fallopian tube strips was determined by tension
      recording. Our results showed that SphK1 and S1P1 were localized in the fallopian
      tube epithelial cells. In addition, smooth muscle cells also contained S1P1.
      Compared with the intrauterine pregnancy group, SPHK1 and S1P1 were overexpressed
      in ectopic pregnancy. However, the S1P concentration within the human oviduct
      from ectopic pregnancy subjects was largely reduced than that from normal
      pregnancy subject. The results from tension recording indicated that exogenous
      and intracellularly generated S1P can regulate the spontaneous contraction of
      oviduct isolated from rats and human. In conclusion, the sphingolipid metabolism
      signal pathway functionally existed in the human fallopian tube. Aberrant
      sphingolipid metabolism in the human fallopian tube may be involved in ectopic
      pregnancy. 

PMID- 23881383
TI  - Diurnal rhythm of a unicellular diazotrophic cyanobacterium under mixotrophic
      conditions and elevated carbon dioxide.
AB  - Mixotrophic cultivation of cyanobacteria in wastewaters with flue gas sparging
      has the potential to simultaneously sequester carbon content from gaseous and
      aqueous streams and convert to biomass and biofuels. Therefore, it was of
      interest to study the effect of mixotrophy and elevated CO2 on metabolism,
      morphology and rhythm of gene expression under diurnal cycles. We chose a
      diazotrophic unicellular cyanobacterium Cyanothece sp. ATCC 51142 as a model,
      which is a known hydrogen producer with robust circadian rhythm. Cyanothece 51142
      grows faster with nitrate and/or an additional carbon source in the growth medium
      and at 3 % CO2. Intracellular glycogen contents undergo diurnal oscillations with
      greater accumulation under mixotrophy. While glycogen is exhausted by midnight
      under autotrophic conditions, significant amounts remain unutilized accompanied
      by a prolonged upregulation of nifH gene under mixotrophy. This possibly supports
      nitrogen fixation for longer periods thereby leading to better growth. To gain
      insights into the influence of mixotrophy and elevated CO2 on circadian rhythm,
      transcription of core clock genes kaiA, kaiB1 and kaiC1, the input pathway, cikA,
      output pathway, rpaA and representatives of key metabolic pathways was analyzed.
      Clock genes' transcripts were lower under mixotrophy suggesting a dampening
      effect exerted by an external carbon source such as glycerol. Nevertheless, the
      genes of the clock and important metabolic pathways show diurnal oscillations in
      expression under mixotrophic and autotrophic growth at ambient and elevated CO2,
      respectively. Taken together, the results indicate segregation of light and dark
      associated reactions even under mixotrophy and provide important insights for
      further applications. 

PMID- 23881385
TI  - Ag/BiPO4 heterostructures: synthesis, characterization and their enhanced
      photocatalytic properties.
AB  - Ag/BiPO4 heterostructures were synthesized by a hydrothermal method combined with
      an impregnation technique. The heterostructures exhibit much higher activity than
      pure BiPO4 for degradation of methylene blue, which may be primarily ascribed to
      highly efficient photogenerated electron-hole pair separation. They also show
      good recyclability and slightly strong absorption in the visible region. In
      addition, the possible mechanism for the enhanced photocatalytic properties of
      Ag/BiPO4 heterostructures is discussed. Moreover, radical scavengers experiments
      confirmed that holes are the main active species instead of hydroxyl radicals
      when coupled with the BiPO4 surface by the noble nanocrystalline metal Ag. 

PMID- 23881384
TI  - Optimization of photosynthesis by multiple metabolic pathways involving
      interorganelle interactions: resource sharing and ROS maintenance as the bases.
AB  - The bioenergetic processes of photosynthesis and respiration are mutually
      beneficial. Their interaction extends to photorespiration, which is linked to
      optimize photosynthesis. The interplay of these three pathways is facilitated by
      two major phenomena: sharing of energy/metabolite resources and maintenance of
      optimal levels of reactive oxygen species (ROS). The resource sharing among
      different compartments of plant cells is based on the production/utilization of
      reducing equivalents (NADPH, NADH) and ATP as well as on the metabolite exchange.
      The responsibility of generating the cellular requirements of ATP and NAD(P)H is
      mostly by the chloroplasts and mitochondria. In turn, besides the chloroplasts,
      the mitochondria, cytosol and peroxisomes are common sinks for reduced
      equivalents. Transporters located in membranes ensure the coordinated movement of
      metabolites across the cellular compartments. The present review emphasizes the
      beneficial interactions among photosynthesis, dark respiration and
      photorespiration, in relation to metabolism of C, N and S. Since the bioenergetic
      reactions tend to generate ROS, the cells modulate chloroplast and mitochondrial
      reactions, so as to ensure that the ROS levels do not rise to toxic levels. The
      patterns of minimization of ROS production and scavenging of excess ROS in
      intracellular compartments are highlighted. Some of the emerging developments are
      pointed out, such as model plants, orientation/movement of organelles and
      metabolomics. 

PMID- 23881386
TI  - Thrombomodulin mediates the migration of cervical cancer cells through the
      regulation of epithelial-mesenchymal transition biomarkers.
AB  - Thrombomodulin (TM) has been shown to regulate many physiological and
      pathological processes, including inflammation, thrombosis, and tumor
      progression. TM is also a natural anticoagulant that maintains circulatory
      homeostasis in endothelial cells. However, little is known regarding the role of
      TM in the progression and metastasis of cervical cancer. TM-specific RNA
      interference and a cDNA expression vector were used to manipulate TM expression
      in cervical cancer cells. Cell growth and cell migration were evaluated using the
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, transwell
      migration assays, and a biosensor system. TM silencing did not affect the growth
      rate of the cells. However, cell migration was dramatically enhanced after
      silencing of TM in HeLa cells. The overexpression of TM in cervical cancer cells
      only slightly influenced their proliferative capacity. After overexpression of TM
      in HeLa cells, their migratory capability was suppressed. Furthermore, we found
      that the decreased expression of E-cadherin and increase of zeb-1 and snail
      expression in TM-silenced cells which may be correlated with the results of
      knocking-down TM increases the migratory ability in this study. Our results
      demonstrate that TM may slightly regulate the growth but played the important
      role in the migratory ability of cervical cancer cells, suggesting that TM could
      potentially serve as a novel prognostic and therapeutic target in cervical
      cancer. 

PMID- 23881387
TI  - Serum-soluble receptor-binding cancer antigen expressed on SiSo cells as a
      clinical marker in lung cancer.
AB  - The aim of this study was to explore the diagnostic value of levels of the serum
      soluble receptor-binding cancer antigen expressed on SiSo cells (sRCAS1)
      expressed in lung cancer patients. Enzyme-linked immunosorbent assay was
      performed to detect serum sRCAS1 levels in 138 patients with lung cancers of
      various types and in 40 healthy controls. Our results showed that the patients
      with lung cancer had higher serum sRCAS1 levels than the controls. As disease
      stages progressed in lung cancer, serum sRCAS1 levels increased; patients with
      lymph node and distant metastases had higher levels than those without
      metastases, regardless of histology, age, and gender. At a cutoff value of 19.2
      U/ml, sRCAS1 was 91.3% sensitive and 72.5% specific for lung cancer. In
      conclusion, these results suggest that sRCAS1 levels could have a clinical value
      for the diagnosis and management of lung cancer and could be used as a new tumor
      marker of lung cancer.

PMID- 23881389
TI  - Screening for trisomy 21 by maternal age fetal nuchal translucency thickness and
      maternal serum sample.
AB  - AIM: The aim of this paper was to examine the performance of two-stage first
      trimester combined screening based on maternal age, fetal nuchal translucency
      (NT) thickness and maternal serum sample "free beta-human chorionic gonadotropin
      (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A)". METHODS: A
      combined screening for chromosomal anomalies was performed in 713 singleton
      pregnancies. We performed a two-stage screening with the blood taken at 8+0 to
      10+6 weeks and the measurement of NT performed at 12+0 to 12+6 weeks. The
      maternal age related risk for trisomy 21 was calculated and adjusted according to
      the gestational age at the time of screening to derive the a-priori risk. The
      measured free beta-human chorionic gonadotropin (beta-hCG) and pregnancy
      associated plasma protein-A (PAPP-A) were converted into a multiple of the median
      (MoM) for gestational age, adjusted for maternal weight, smoking status,
      ethnicity, method of conception (spontaneous or IVF) and parity. The measured NT
      was assessed in relationship of mesasure of CRL. Finally, the risk resulting by
      NT thickness and biochemical markers were multiplied by the a-priori risk to
      derive the patient-specific risk. RESULTS: The ultrascreen was considered
      positive in the case where the risk was greater than 1:250. In this case it was
      suggested the study of the fetal karyotype through an invasive test. In our study
      we had 23 positive cases after the combined screening: all patients have opted
      for the study of fetal karyotype, and in 5 cases the result was abnormal (trisomy
      21). We had 1 case where the test was negative but the fetal karyotype was
      abnormal (trisomy 21). We have calculated sensitivity and false positive rate of
      the test. CONCLUSION: In our study there were 707 cases with a normal karyotype
      or delivery of a phenotypically normal baby and 6 cases with trisomy 21. The
      detection rate of the first trimester screening for chromosomal anomalies was 83%
      with a false positive rate of 3,2%. The aim of the study was estimated the
      performance of two-step strategy screening. In our study, the performance of the
      screening model, based on the two-stage, was not higher than the performance of
      screening based on a single-step reported in literature. In our opinion, there is
      no potential advantage in terms of detection rate.

PMID- 23881390
TI  - [Phytoestrogens and menopause].
AB  - Menopause is the interruption of menstrual and reproductive capacity, therefore,
      that occurs naturally in all women between 48 and 55 years, due to a lower
      production of gonadal steroids. The period becomes progressively irregular and
      lack of ovulation and menstrual flow decrease, and finally disappears. The time
      between the first symptoms and the cessation of the menstrual cycle is called
      menopause. With the onset of menopause the woman undergoes a series of changes
      related to estrogen deficiency, which occur in all tissues of the body. In this
      period one can distinguish an early stage, characterized by hot flashes, mood
      swings, night sweats and insomnia, and a late phase in which we highlight more
      symptoms related to the interruption of hormonal such as osteoporosis, obesity,
      at urogenital and increased incidence of cardiovascular disease. In Italy, only
      5.2% of women aged 45-64 years used hormone replacement therapy, and only 20-30%
      follow a therapy for more than two years, both for psychological reasons, and for
      fear of side effects. Not surprisingly, therefore, phytoestrogens are given a
      high importance, as they are considered a natural alternative tank to to their
      plant origin. Interest in phytoestrogens was born from the observation that
      postmenopausal women who live in the East have a lower incidence of symptoms,
      cardiovascular disease, cancer and osteoporosis hormone use, compared to Western
      women. 

PMID- 23881388
TI  - TIMP1 overexpression mediates resistance of MCF-7 human breast cancer cells to
      fulvestrant and down-regulates progesterone receptor expression.
AB  - High levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP1) are associated
      with poor prognosis, reduced response to chemotherapy, and, potentially, also
      poor response to endocrine therapy in breast cancer patients. Our objective was
      to further investigate the hypothesis that TIMP1 is associated with endocrine
      sensitivity. We established a panel of 11 MCF-7 subclones with a wide range of
      TIMP1 mRNA and protein expression levels. Cells with high expression of TIMP1
      versus low TIMP1 displayed significantly reduced sensitivity to the antiestrogen
      fulvestrant (ICI 182,780, Faslodex(r)), while TIMP1 levels did not influence the
      sensitivity to 4-hydroxytamoxifen. An inverse correlation between expression of
      the progesterone receptor and TIMP1 was found, but TIMP1 levels did not correlate
      with estrogen receptor levels or growth-promoting effects of estrogen (estradiol,
      E2). Additionally, the effects of fulvestrant, 4-hydroxytamoxifen, or estrogen on
      estrogen receptor expression were not associated with TIMP1 levels. Gene
      expression analyses revealed associations between expression of TIMP1 and genes
      involved in metabolic pathways, epidermal growth factor receptor 1/cancer
      signaling pathways, and cell cycle. Gene and protein expression analyses showed
      no general defects in estrogen receptor signaling except from lack of
      progesterone receptor expression and estrogen inducibility in clones with high
      TIMP1. The present study suggests a relation between high expression level of
      TIMP1 and loss of progesterone receptor expression combined with fulvestrant
      resistance. Our findings in vitro may have clinical implications as the data
      suggest that high tumor levels of TIMP1 may be a predictive biomarker for reduced
      response to fulvestrant. 

PMID- 23881391
TI  - Betulinic acid and possible influence on the clearance of Human Papilloma Virus:
      cytological and virological follow-up.
AB  - AIM: Persistent infection with high-risk Human Papilloma Virus (HPV) types is
      considered necessary for the development of cervical cancer. No such efficient
      antiviral agent exists at the present time. The aim of this study was to assess
      whether the use of topical products, vaginal ovules, containing betulinic acid
      and betulin may influence viral replication in vivo by promoting its negativity.
      METHODS: We enrolled 62 patients at the colposcopy ambulatory with negative
      colposcopy or with congenital ectopic or normal transformation zone, but with HPV
      test positive for high risk. We divided the patients into two groups: group A had
      no kind of treatment, group B has undergone a treatment with vaginal ovules
      containing betulinic acid and betulin. All patients have taken a new HPV-test six
      months after the first control. RESULTS: After six months, we compared the
      percentage of negative HPV-test. We observed a percentage of negativity of 93% in
      group B versus 68% in group A. The data was statistically significant at chi2
      test (P<0,05). CONCLUSION: We believe that the results should be investigated
      further to confirm if there is a correlation between these substances and the
      increase in the rate of viral negativity.

PMID- 23881392
TI  - Long-term outcomes of perineal rehabilitation.
AB  - AIM: Pelvic floor muscle training (PFMT) is classified with a level 1 evidence
      and a grade A recommendation, but long term effects have not been studied
      thoroughly. This study aims at assessing the long-term effectiveness of perineal
      rehabilitation on patients with mild prolapse and pure stress urinary
      incontinence (IUS) symptoms. METHODS: Retrospective observational study on 49
      patients examined at the beginning of the observation and 60 months after
      receiving biofeedback assisted PFMT. We created two groups. Group A: 27 women
      with mild symptoms of prolapse and pure mild IUS; Group B: 22 symptomatic
      patients postsurgery. We considered as therapeutic success a 50% general
      reduction of the symptoms experienced by the patients in terms of reduction of
      leakage episodes, number of pads used, strength and endurance of the
      pubococcygeus muscle and initial prolapse signs/symptoms. RESULTS: Group A
      (follow-up 60 months): Reduction of prolapse symptoms: cured/much improved: 65%
      (17 patients); worsened: 22.4% (6 patients); unchanged: 18.5% (5 patients);
      reduction of urinary symptoms: cured/much improved: 59.3% (16 patients); surgery:
      40.7% (11 patients); group B (follow-up 60 months); cured: 55.5% (12 patients);
      much improved: 44% (10 patients). CONCLUSION: In conclusion, as for the treatment
      of menopausal patients with symptoms of mild disorders of the urinary/genital
      system, excellent results were reported in women underwent rehabilitation, as a
      first approach or after failed TVT-O.

PMID- 23881393
TI  - Genetic regulation of cold-induced albinism in the maize inbred line A661.
AB  - In spite of multiple studies elucidating the regulatory pathways controlling
      chlorophyll biosynthesis and photosynthetic activity, little is known about the
      molecular mechanism regulating cold-induced chlorosis in higher plants. Herein
      the characterization of the maize inbred line A661 which shows a cold-induced
      albino phenotype is reported. The data show that exposure of seedlings to low
      temperatures during early leaf biogenesis led to chlorophyll losses in this
      inbred. A661 shows a high plasticity, recovering resting levels of photosynthesis
      activity when exposed to optimal temperatures. Biochemical and transcriptome data
      indicate that at suboptimal temperatures chlorophyll could not be fully
      accommodated in the photosynthetic antenna in A661, remaining free in the
      chloroplast. The accumulation of free chlorophyll activates the expression of an
      early light inducible protein (elip) gene which binds chlorophyll to avoid cross
      reactions that could lead to the generation of harmful reactive oxygen species.
      Higher levels of the elip transcript were observed in plants showing a cold
      induced albino phenotype. Forward genetic analysis reveals that a gene located on
      the short arm of chromosome 2 regulates this protective mechanism. 

PMID- 23881394
TI  - Structural and physiological analyses in Salsoleae (Chenopodiaceae) indicate
      multiple transitions among C3, intermediate, and C4 photosynthesis.
AB  - In subfamily Salsoloideae (family Chenopodiaceae) most species are C4 plants
      having terete leaves with Salsoloid Kranz anatomy characterized by a continuous
      dual chlorenchyma layer of Kranz cells (KCs) and mesophyll (M) cells, surrounding
      water storage and vascular tissue. From section Coccosalsola sensu Botschantzev,
      leaf structural and photosynthetic features were analysed on selected species of
      Salsola which are not performing C4 based on leaf carbon isotope composition. The
      results infer the following progression in distinct functional and structural
      forms from C3 to intermediate to C4 photosynthesis with increased leaf succulence
      without changes in vein density: From species performing C3 photosynthesis with
      Sympegmoid anatomy with two equivalent layers of elongated M cells, with few
      organelles in a discontinuous layer of bundle sheath (BS) cells (S. genistoides,
      S. masenderanica, S. webbii) > development of proto-Kranz BS cells having
      mitochondria in a centripetal position and increased chloroplast number (S.
      montana) > functional C3-C4 intermediates having intermediate CO2 compensation
      points with refixation of photorespired CO2, development of Kranz-like anatomy
      with reduction in the outer M cell layer to hypodermal-like cells, and increased
      specialization (but not size) of a Kranz-like inner layer of cells with increased
      cell wall thickness, organelle number, and selective expression of mitochondrial
      glycine decarboxylase (Kranz-like Sympegmoid, S. arbusculiformis; and Kranz-like
      Salsoloid, S. divaricata) > selective expression of enzymes between the two cell
      types for performing C4 with Salsoloid-type anatomy. Phylogenetic analysis of
      tribe Salsoleae shows the occurrence of C3 and intermediates in several clades,
      and lineages of interest for studying different forms of anatomy. 

PMID- 23881395
TI  - Regulation of plant vascular stem cells by endodermis-derived EPFL-family peptide
      hormones and phloem-expressed ERECTA-family receptor kinases.
AB  - Plant vasculatures are complex tissues consisting of (pro)cambium, phloem, and
      xylem. The (pro)cambium serves as vascular stem cells that produce all vascular
      cells. The Arabidopsis ERECTA (ER) receptor kinase is known to regulate the
      architecture of inflorescence stems. It was recently reported that the er
      mutation enhances a vascular phenotype induced by a mutation of TDR/PXY, which
      plays a significant role in procambial proliferation, suggesting that ER
      participates in vascular development. However, detailed molecular mechanisms of
      the ER-dependent vascular regulation are largely unknown. Here, this work found
      that ER and its paralogue, ER-LIKE1, were redundantly involved in procambial
      development of inflorescence stems. Interestingly, their activity in the phloem
      was sufficient for vascular regulation. Furthermore, two endodermis-derived
      peptide hormones, EPFL4 and EPFL6, were redundantly involved in such regulation.
      It has been previously reported that EPFL4 and EPFL6 act as ligands of phloem
      expressed ER for stem elongation. Therefore, these findings indicate that cell
      cell communication between the endodermis and the phloem plays an important role
      in procambial development as well as stem elongation. Interestingly, similar EPFL
      ER modules control two distinct developmental events by slightly changing their
      components: the EPFL4/6-ER module for stem elongation and the EPFL4/6-ER/ERL1
      module for vascular development. 

PMID- 23881396
TI  - RLP1.1, a novel wheat receptor-like protein gene, is involved in the defence
      response against Puccinia striiformis f. sp. tritici.
AB  - Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the
      most serious diseases of wheat; therefore, exploring effective resistance-related
      genes is critical for breeding and studying resistance mechanisms. However, only
      a few stripe rust resistance genes and defence-related genes have been cloned.
      Moreover, transgenic wheat with enhanced stripe rust resistance has rarely been
      reported. Receptor-like proteins (RLPs) are known to be involved in defence and
      developmental pathways. In this research, a novel RLP gene TaRLP1.1 was
      characterized as an important stripe rust defence gene. TaRLP1.1 was screened by
      GeneChip and was found to be induced by Pst specifically in the resistant
      variety. Knock down of TaRLP1.1 in the stripe rust-resistant plants resulted in
      increased susceptibility to Pst, and phenolic autofluorogen accumulation at the
      pathogen-host interaction sites, usually correlated with the hypersensitive
      response, was decreased dramatically. However, when the TaRLP1.1 gene was
      transformed into the susceptible wheat variety Yangmai158, the transgenic plants
      showed highly increased resistance to Pst, and the hypersensitive response was
      enhanced at the infection sites. Meanwhile, the expression of pathogenesis
      related genes decreased in the TaRLP1.1-silenced plants and increased in the
      TaRLP1.1-overexpressing plants. Thus, it was proposed that TaRLP1.1 greatly
      contributed to the hypersensitive response during the pathogen-host interaction.
      Along with the functional analysis, an evolutionary study of the TaRLP1 family
      was performed. Characterization of TaRLP1.1 may facilitate breeding for stripe
      rust resistance and better understanding of the evolution of the RLP genes in
      wheat. 

PMID- 23881397
TI  - Deletion of chloroplast NADPH-dependent thioredoxin reductase results in
      inability to regulate starch synthesis and causes stunted growth under short-day
      photoperiods.
AB  - Plastid-localized NADPH-dependent thioredoxin reductase C (NTRC) is a unique NTR
      enzyme containing both reductase and thioredoxin domains in a single polypeptide.
      Arabidopsis thaliana NTRC knockout lines (ntrc) show retarded growth, especially
      under short-day (SD) photoperiods. This study identified chloroplast processes
      that accounted for growth reduction in SD-acclimated ntrc. The strongest
      reduction in ntrc growth occurred under photoperiods with nights longer than 14
      h, whereas knockout of the NTRC gene did not alter the circadian-clock-controlled
      growth of Arabidopsis. Lack of NTRC modulated chloroplast reactive oxygen species
      (ROS) metabolism, but oxidative stress was not the primary cause of retarded
      growth of SD-acclimated ntrc. Scarcity of starch accumulation made ntrc leaves
      particularly vulnerable to photoperiods with long nights. Direct interaction of
      NTRC and ADP-glucose pyrophosphorylase, a key enzyme in starch synthesis, was
      confirmed by yeast two-hybrid analysis. The ntrc line was not able to maximize
      starch synthesis during the light period, which was particularly detrimental
      under SD conditions. Acclimation of Arabidopsis to SD conditions also involved an
      inductive rise of ROS production in illuminated chloroplasts that was not
      counterbalanced by the activation of plastidial anti-oxidative systems. It is
      proposed that knockout of NTRC challenges redox regulation of starch synthesis,
      resulting in stunted growth of the mutant lines acclimated to the SD photoperiod.

PMID- 23881398
TI  - Transcriptional analysis through RNA sequencing of giant cells induced by
      Meloidogyne graminicola in rice roots.
AB  - One of the reasons for the progressive yield decline observed in aerobic rice
      production is the rapid build-up of populations of the rice root knot nematode
      Meloidogyne graminicola. These nematodes induce specialized feeding cells inside
      root tissue, called giant cells. By injecting effectors in and sipping
      metabolites out of these cells, they reprogramme normal cell development and
      deprive the plant of its nutrients. In this research we have studied the
      transcriptome of giant cells in rice, after isolation of these cells by laser
      capture microdissection. The expression profiles revealed a general induction of
      primary metabolism inside the giant cells. Although the roots were shielded from
      light induction, we detected a remarkable induction of genes involved in
      chloroplast biogenesis and tetrapyrrole synthesis. The presence of chloroplast
      like structures inside these dark-grown cells was confirmed by confocal
      microscopy. On the other hand, genes involved in secondary metabolism and more
      specifically, the majority of defence-related genes were strongly suppressed in
      the giant cells. In addition, significant induction of transcripts involved in
      epigenetic processes was detected inside these cells 7 days after infection. 

PMID- 23881400
TI  - Emissions of putative isoprene oxidation products from mango branches under
      abiotic stress.
AB  - Although several per cent of net carbon assimilation can be re-released as
      isoprene emissions to the atmosphere by many tropical plants, much uncertainty
      remains regarding its biological significance. In a previous study, we detected
      emissions of isoprene and its oxidation products methyl vinyl ketone (MVK) and
      methacrolein (MACR) from tropical plants under high temperature/light stress,
      suggesting that isoprene is oxidized not only in the atmosphere but also within
      plants. However, a comprehensive analysis of the suite of isoprene oxidation
      products in plants has not been performed and production relationships with
      environmental stress have not been described. In this study, putative isoprene
      oxidation products from mango (Mangifera indica) branches under abiotic stress
      were first identified. High temperature/light and freeze-thaw treatments verified
      direct emissions of the isoprene oxidation products MVK and MACR together with
      the first observations of 3-methyl furan (3-MF) and 2-methyl-3-buten-2-ol (MBO)
      as putative novel isoprene oxidation products. Mechanical wounding also
      stimulated emissions of MVK and MACR. Photosynthesis under (13)CO2 resulted in
      rapid (<30 min) labelling of up to five carbon atoms of isoprene, with a similar
      labelling pattern observed in the putative oxidation products. These observations
      highlight the need to investigate further the mechanisms of isoprene oxidation
      within plants under stress and its biological and atmospheric significance.

PMID- 23881399
TI  - Association study of wheat grain protein composition reveals that gliadin and
      glutenin composition are trans-regulated by different chromosome regions.
AB  - Wheat grain storage protein (GSP) content and composition are the main
      determinants of the end-use value of bread wheat (Triticum aestivum L.) grain.
      The accumulation of glutenins and gliadins, the two main classes of GSP in wheat,
      is believed to be mainly controlled at the transcriptional level through a
      network of transcription factors. This regulation network could lead to stable
      cross-environment allometric scaling relationships between the quantity of GSP
      classes/subunits and the total quantity of nitrogen per grain. This work
      conducted a genetic mapping study of GSP content and composition and allometric
      scaling parameters of grain N allocation using a bread wheat worldwide core
      collection grown in three environments. The core collection was genotyped with
      873 markers for genome-wide association and 167 single nucleotide polymorphism
      markers in 51 candidate genes for candidate association. The candidate genes
      included 35 transcription factors (TFs) expressed in grain. This work identified
      74 loci associated with 38 variables, of which 19 were candidate genes or were
      tightly linked with candidate genes. Besides structural GSP genes, several loci
      putatively trans-regulating GSP accumulation were identified. Seven candidate
      TFs, including four wheat orthologues of barley TFs that control hordein gene
      expression, were associated or in strong linkage disequilibrium with markers
      associated with the composition or quantity of glutenin or gliadin, or allometric
      grain N allocation parameters, confirming the importance of the transcriptional
      control of GSP accumulation. Genome-wide association results suggest that the
      genes regulating glutenin and gliadin compositions are mostly distinct from each
      other and operate differently. 

PMID- 23881401
TI  - Single centre observational study to evaluate the safety and efficacy of the
      ProceedTM Ventral Patch to repair small ventral hernias.
AB  - BACKGROUND: There is evidence that mesh repair for primary umbilical hernias
      results in less recurrences and similar wound complication rates compared to
      tissue repair. In recent years, several mesh devices for the repair of small
      ventral hernias have been developed, but some reports have been published on
      serious complications and adverse effects encountered with those mesh devices.
      METHODS: The ProceedTM Ventral Patch (PVPTM) is a partially absorbable
      lightweight polypropylene mesh. We introduced PVPTM in our department in April
      2009 and collected patient data and outcome in an observational study of 101
      consecutive patients until December 2011 (Clinical.Trials.gov: NCT01307696). In
      addition to the routine control 3 weeks postoperative, prospective follow-up
      included a questionnaire, clinical investigation and ultrasound after 12 months.
      RESULTS: The study included 91 primary (76 umbilical/15 epigastric) and 10
      incisional ventral hernias (including 6 trocar hernias). In all patients a PVPTM
      with a diameter of 6.4 cm was used. Wound problems were the most frequent
      complication (n = 18). Follow-up of at least 12 months was achieved in 98
      patients (97 %) and the mean follow-up time was 15.9 months. Follow-up by
      clinical examination diagnosed a recurrence in 11/92 patients (12.0 %). Only four
      patients were aware of their recurrent hernia, the seven others reported no
      problems in the questionnaire. The additional ultrasound performed did not reveal
      recurrences that were not already diagnosed by clinical examination. In five
      patients a reoperation for repair of the recurrence was performed (reoperation
      rate 5/98 = 5.1 %). Hernia defect size (p = 0.032) and type of hernia (p = 0.029)
      were found to be a significant risk factors for development of a recurrent hernia
      (Fisher's exact test). Hernia size was a significant risk factor both in a
      univariate (p = 0.005) and in a multivariate Cox model (p = 0.017). Incisional
      hernia was of borderline significance in a univariate (p = 0.047) and in a
      multivariate Cox model (p = 0.08). CONCLUSION: Intensive clinical follow-up
      yields a high percentage (12.0 %) of clinically proven, but often asymptomatic
      recurrences after repair of small ventral hernias with the PVPTM. Reoperation
      rate for recurrence was 5.1 %. Hernia defect size is a significant risk factor
      for recurrence. Therefore, we recommend using the PVPTM only for primary ventral
      hernias smaller than 2 cm. For larger or incisional hernias other techniques
      allowing the use of larger meshes is advocated.

PMID- 23881402
TI  - Competitive binding of natural amphiphiles with graphene derivatives.
AB  - Understanding the transformation of graphene derivatives by natural amphiphiles
      is essential for elucidating the biological and environmental implications of
      this emerging class of engineered nanomaterials. Using rapid discrete-molecular
      dynamics simulations, we examined the binding of graphene and graphene oxide with
      peptides, fatty acids, and cellulose, and complemented our simulations by
      experimental studies of Raman spectroscopy, FTIR, and UV-Vis spectrophotometry.
      Specifically, we established a connection between the differential binding and
      the conformational flexibility, molecular geometry, and hydrocarbon content of
      the amphiphiles. Importantly, our dynamics simulations revealed a Vroman-like
      competitive binding of the amphiphiles for the graphene oxide substrate. This
      study provides a mechanistic basis for addressing the transformation, evolution,
      transport, biocompatibility, and toxicity of graphene derivatives in living
      systems and the natural environment. 

PMID- 23881403
TI  - Cooperation among Numb, MDM2 and p53 in the development and progression of
      pancreatic cancer.
AB  - We study the expression of Numb, MDM2 and p53 for clinical significance in
      pancreatic cancer (PC) and their functional relationship in regulating biological
      behaviors of PC cells. IHC, IB and qRT-PCR were used to detect Numb, MDM2 and p53
      expression in PC. Transfection and drug intervention were used to investigate
      their functional relationship in PC cells. IHC showed that Numb expression was
      negatively associated with tumor size, differentiation and UICC stage, while
      expression of MDM2 and p53 was positively associated with tumor T and UICC
      stages, respectively (P < 0.05). Numb was an independent prognostic indicator in
      PC (P < 0.05). Patients with Numb-positive expression or combined with MDM2
      negative expression had a significantly better overall survival (P < 0.05).
      Altered expression of Numb can regulate wild-type but not mutant p53 expression,
      while MDM2 knockdown increased Numb but not mutant p53 protein level. Meanwhile,
      Numb knockdown increased chemoresistance but decreased activated p53 and cleaved
      caspase-3 protein expression in gemcitabine-treated Capan-2 cells. Moreover, Numb
      co-immunoprecipitated with p53 to prevent p53 ubiquitin-dependent protein
      degradation and this ubiquitin-dependent regulation plays an important role in
      the coordinate function of these three proteins on cell invasion and migration in
      PC cells. Our study is the first to demonstrate the clinical significance and
      functional cooperation among Numb, MDM2 and p53 involved in the development and
      progression of PC.

PMID- 23881404
TI  - High-fat diet ingestion correlates with neuropathy in the duodenum myenteric
      plexus of obese mice with symptoms of type 2 diabetes.
AB  - Obesity and type 2 diabetes are increasing in prevalence at an alarming rate in
      developed and developing nations and over 50% of patients with prolonged stages
      of disease experience forms of autonomic neuropathy. These patients have symptoms
      indicating disrupted enteric nervous system function including gastric
      discomfort, gastroparesis and intestinal dysmotility. Previous assessments have
      examined enteric neuronal injury within either type 1 diabetic or transgenic type
      2 diabetic context. This study aims to assess damage to myenteric neurons within
      the duodenum of high-fat diet ingesting mice experiencing symptoms of type 2
      diabetes, as this disease context is most parallel to the human condition and
      disrupted duodenal motility underlies negative gastrointestinal symptoms. Mice
      fed a high-fat diet developed symptoms of obesity and diabetes by 4 weeks. After
      8 weeks, the total number of duodenal myenteric neurons and the synaptophysin
      density index were reduced and transmission electron microscopy showed axonal
      swelling and loss of neurofilaments and microtubules, suggesting compromised
      neuronal health. High-fat diet ingestion correlated with a loss of neurons
      expressing VIP and nNOS but did not affect the expression of ChAT, substance P,
      calbindin and CGRP. These results correlate high-fat diet ingestion, obesity and
      type 2 diabetes symptoms with a loss of duodenal neurons, biasing towards those
      with inhibitory nature. This pathology may underlie dysmotility and other
      negative GI symptoms experienced by human type 2 diabetic and obese patients.

PMID- 23881405
TI  - Neuroimmunomodulation in human autoimmune liver disease.
AB  - Bidirectional interaction between immune and nervous systems is considered an
      important biological process in health and disease. However, little is known
      about the mechanisms involved in their interaction in the human liver. This study
      examines the distribution of intrahepatic NPY, SP immunoreactive (IR) nerve
      fibers and their antomical relationship with immunocells containing tumor
      necrosis factor-alpha (TNF-alpha) and nuclear factor kappaB (NF-kappaB) in
      patients with autoimmune hepatitis. Liver specimens were obtained from control
      liver and autoimmune hepatitis patients. The immunoreactivity was determined by
      immunohisto- and immunocytochemistry and confocal laser microscopy. In hepatitis,
      the number of NPY-IR and SP-IR nerve fibers increased significantly. These IR
      nerve fibers were in very close contact with the lymphocytes. In healthy
      controls, no NPY-IR, SP-IR or NF-kappaB IR lymphocytes and only a few TNF-alpha
      positive cells, were observed. In hepatitis, some of the lymphocytes showed
      immunoreactivity for SP and NPY in the portal area. Fluorescent double-labeled
      immunostaining revealed that in these cells NPY did not colocalize with TNF-alpha
      or NF-kappaB. However, some of the SP fluorescence-positive immune cells
      exhibited immunostaining for p65 of NF-kappaB, where their labeling was detected
      in the nuclei. Under the electronmicroscope, these cells could be identified
      (lymphocytes, plasmacells and mast cells). The gap between the IR nerve fibers
      and immunocells was 1 MUm or even less. Overexpression of SP in lymphocytes may
      amplify local inflammation, while NPY may contribute to liver homeostasis in
      hepatitis. Neural immunomodulation (SP antagonists and NPY) might be a novel
      therapeutic concept in the management of liver inflammation.

PMID- 23881406
TI  - Expression of neuropeptides and anoctamin 1 in the embryonic and adult zebrafish
      intestine, revealing neuronal subpopulations and ICC-like cells.
AB  - This immunohistochemical study in zebrafish aims to extend the neurochemical
      characterization of enteric neuronal subpopulations and to validate a marker for
      identification of interstitial cells of Cajal (ICC). The expression of
      neuropeptides and anoctamin 1 (Ano1), a selective ICC marker in mammals, was
      analyzed in both embryonic and adult intestine. Neuropeptides were present from 3
      days postfertilization (dpf). At 3 dpf, galanin-positive nerve fibers were found
      in the proximal intestine, while calcitonin gene-related peptide (CGRP)- and
      substance P-expressing fibers appeared in the distal intestine. At 5 dpf,
      immunoreactive fibers were present along the entire intestinal length, indicating
      a well-developed peptidergic innervation at the onset of feeding. In the adult
      intestine, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase
      activating peptide (PACAP), galanin, CGRP and substance P were detected in nerve
      fibers. Colchicine pretreatment enhanced only VIP and PACAP immunoreactivity. VIP
      and PACAP were coexpressed in enteric neurons. Colocalization stainings revealed
      three neuronal subpopulations expressing VIP and PACAP: a nitrergic
      noncholinergic subpopulation, a serotonergic subpopulation and a subpopulation
      expressing no other markers. Ano1-immunostaining revealed a 3-dimensional network
      in the adult intestine containing multipolar cells at the myenteric plexus and
      bipolar cells interspersed between circular smooth muscle cells. Ano1
      immunoreactivity first appeared at 3 dpf, indicative of the onset of
      proliferation of ICC-like cells. It is shown that the Ano1 antiserum is a
      selective marker of ICC-like cells in the zebrafish intestine. Finally, it is
      hypothesized that ICC-like cells mediate the spontaneous regular activity of the
      embryonic intestine.

PMID- 23881407
TI  - Characterization of a pituitary-tumor-derived cell line, TtT/GF, that expresses
      Hoechst efflux ABC transporter subfamily G2 and stem cell antigen 1.
AB  - The anterior lobe of the pituitary gland is composed of five types of endocrine
      cells and of non-endocrine folliculo-stellate cells that produce various local
      signaling molecules. The TtT/GF cell line is derived from pituitary tumors,
      produces no hormones and has folliculo-stellate cell-like characteristics. The
      biological function of TtT/GF cells remains elusive but several properties have
      been postulated (support of endocrine cells, control of cell proliferation,
      scavenger function). Recently, we observed that TtT/GF cells have high resistance
      to the antibiotic G418 and low influx for Hoechst 33342, indicating the presence
      of ATP-binding cassette (ABC) transporters that efflux multiple drugs, i.e., a
      property similar to that of stem/progenitor cells. Therefore, we examine TtT/GF
      cells for the presence of ABC transporters, for the efflux ability of Hoechst
      33342 and for those genes characteristic of TtT/GF cells. Real-time polymerase
      chain reaction (PCR) for ABC transporters demonstrated that Abcb1a, Abcb1b and
      Abcg2, regarded as stem cell markers, were characteristically expressed in TtT/GF
      cells but not in Tpit/F1 and LbetaT2 cells. Furthermore, the remarkable low
      efflux ability of Hoechst 33342 from TtT/GF cells was confirmed by using
      inhibitors and contrasted with the abilities of Tpit/F1 and LbetaT2 cells. The
      high and specific expression of stem cell antigen 1 (Sca1) in TtT/GF cells was
      confirmed by real-time PCR. We also demonstrated those genes that are expressed
      abundantly and characteristically in TtT/GF, suggesting that TtT/GF cells have
      unique characteristics similar to those of stem/progenitor cells of endothelial
      or mesenchymal origin. Thus, the present study has revealed an intriguing
      property of TtT/GF cells, providing a new clue for an understanding of the
      function of this cell line. 

PMID- 23881408
TI  - Histological analysis of mammary gland remodeling caused by lipopolysaccharide in
      lactating mice.
AB  - The mammary alveolus is a highly specialized structure that secretes milk for
      suckling infants during lactation. The secreting alveolus consists in alveolar
      epithelial cells (AECs) and myoepithelial cells and is surrounded by
      microvascular endothelial cells, adipocytes and several immune cell types such as
      macrophages and neutrophils. During normal lactation, these cells play distinct
      roles needed to maintain the secretory ability of the mammary alveolus. However,
      inflammation resulting from pathogenic bacterial infections causes structural and
      functional regression of the secreting alveolus in the lactating mammary gland.
      We initiated artificial inflammation in the mammary glands of lactating mice by
      injecting lipopolysaccharide (LPS), as a mammary inflammation model and
      investigated, by immunohistochemical analysis, the early response of the cells
      constituting and surrounding the alveolus. Some AECs sloughed away from the
      alveolar epithelial layer and showed progression of apoptosis detected by
      immunostaining of cleaved caspase-3 after LPS injection. Adipocytes exhibited
      transient shrinkage and re-accumulation of lipid droplets, although the numbers
      of adipocytes did not demonstrate a significant difference. Activation of F4/80
      positive cells around the mammary alveolus was observed 3 h after LPS injection.
      However, the recruitment of CD11b-positive cells into the alveolar lumen was not
      observed until 12 h after LPS injection. Myoepithelial cells were contracted
      after LPS injection. LPS injection around the alveolus did not induce any
      detectable structural changes in capillaries surrounding the alveolus. Thus, cell
      specific behavior and tissue remodeling of the alveolus occur after LPS injection
      in a time-dependent manner.

PMID- 23881409
TI  - Site-specific gene expression and localization of growth factor ligand receptors
      RET, GFRalpha1 and GFRalpha2 in human adult colon.
AB  - Two of the glial-cell-line-derived neurotrophic factor (GDNF) family ligands
      (GFLs), namely GDNF and neurturin (NRTN), are essential neurotropic factors for
      enteric nerve cells. Signal transduction is mediated by a receptor complex
      composed of GDNF family receptor alpha 1 (GFRalpha1) for GDNF or GFRalpha2 for
      NRTN, together with the tyrosine kinase receptor RET (rearranged during
      transfection). As both factors and their receptors are crucial for enteric neuron
      survival, we assess the site-specific gene expression of these GFLs and their
      corresponding receptors in human adult colon. Full-thickness colonic specimens
      were obtained after partial colectomy for non-obstructing colorectal carcinoma.
      Samples were processed for immunohistochemistry and co-localization studies. Site
      specific gene expression was determined by real-time quantitative polymerase
      chain reaction in enteric ganglia and in circular and longitudinal muscle
      harvested by microdissection. Protein expression of the receptors was mainly
      localized in the myenteric and submucosal plexus. Dual-label immunohistochemistry
      with PGP 9.5 as a pan-neuronal marker detected immunoreactivity of the receptors
      in neuronal somata and ganglionic neuropil. RET immunoreactivity co-localized
      with neuronal GFRalpha1 and GFRalpha2 signals. The dominant source of receptor
      mRNA expression was in myenteric ganglia, whereas both GFLs showed higher
      expression in smooth muscle layers. The distribution and expression pattern of
      GDNF and NRTN and their corresponding receptors in the human adult enteric
      nervous system indicate a role of both GFLs not only in development but also in
      the maintenance of neurons in adulthood. The data also provide a basis for the
      assessment of disturbed signaling components of the GDNF and NRTN system in
      enteric neuropathies underlying disorders of gastrointestinal motility. 

PMID- 23881410
TI  - The flavor of pomegranate fruit: a review.
AB  - Despite the increasing commercial importance of pomegranate, especially because
      of its recently discovered health-promoting benefits, relatively little is yet
      known regarding its sensory quality and flavor preferences, or about the
      biochemical constituents that determine its sensory characteristics. The
      perceived flavor of pomegranate fruit results from the combination of various
      taste, aroma and mouthfeel sensations. The taste is governed mainly by the
      presence of sugars (glucose and fructose) and organic acids (primarily citric and
      malic acids). The aroma evolves from the presence of dozens of volatiles,
      including alcohols, aldehydes, ketones, and terpenes, which provide a mixture of
      various 'green', 'woody', 'earthy', 'fruity', 'floral', 'sweet' and 'musty'
      notes. In addition, the sensory satisfaction during the eating of pomegranate
      arils is complemented by various mouthfeel sensations, including seed hardness
      and astringency sensations. In the present review we will describe the sensory
      quality and flavor preferences of pomegranate fruit, including the genetic
      diversity in flavor characteristics among distinct varieties. In addition, we
      will describe the dynamic changes that occur in fruit flavor during fruit
      ripening and postharvest storage.

PMID- 23881411
TI  - Phased, secondary, small interfering RNAs in posttranscriptional regulatory
      networks.
AB  - Plant genomes are the source of large numbers of small RNAs, generated via a
      variety of genetically separable pathways. Several of these pathways converge in
      the production of phased, secondary, small interfering RNAs (phasiRNAs),
      originally designated as trans-acting small interfering RNAs or tasiRNAs.
      PhasiRNA biogenesis requires the involvement of microRNAs as well as the cellular
      machinery for the production of siRNAs. PhasiRNAs in Arabidopsis thaliana have
      been well described for their ability to function in trans to suppress target
      transcript levels. Plant genomic data from an expanding set of species have
      demonstrated that Arabidopsis is relatively sparing in its use of phasiRNAs,
      while other genomes contain hundreds or even thousands of phasiRNA-generating
      loci. In the dicots, targets of those phasiRNAs include several large or
      conserved families of genes, such as those encoding disease resistance proteins
      or transcription factors. Suppression of nucleotide-binding, leucine-rich repeat
      (NB-LRR) disease resistance genes by small RNAs is particularly unusual because
      of a high level of redundancy. In this review, we discuss plant phasiRNAs and the
      possible mechanistic significance of phasiRNA-based regulation of the NB-LRRs. 

PMID- 23881413
TI  - On the origin of C4 species in yellowtops.

PMID- 23881414
TI  - Folate polyglutamylation is involved in chromatin silencing by maintaining global
      DNA methylation and histone H3K9 dimethylation in Arabidopsis.
AB  - DNA methylation and repressive histone Histone3 Lysine9 (H3K9) dimethylation
      correlate with chromatin silencing in plants and mammals. To identify factors
      required for DNA methylation and H3K9 dimethylation, we screened for suppressors
      of the repressor of silencing1 (ros1) mutation, which causes silencing of the
      expression of the RD29A (RESPONSE TO DESSICATION 29A) promoter-driven luciferase
      transgene (RD29A-LUC) and the 35S promoter-driven NPTII (NEOMYCIN
      PHOSPHOTRANSFERASE II) transgene (35S-NPTII). We identified the
      folylpolyglutamate synthetase FPGS1 and the known factor DECREASED DNA
      METHYLATION1 (DDM1). The fpgs1 and ddm1 mutations release the silencing of both
      RD29A-LUC and 35S-NPTII. Genome-wide analysis indicated that the fpgs1 mutation
      reduces DNA methylation and releases chromatin silencing at a genome-wide scale.
      The effect of fpgs1 on chromatin silencing is correlated with reduced levels of
      DNA methylation and H3K9 dimethylation. Supplementation of fpgs1 mutants with 5
      formyltetrahydrofolate, a stable form of folate, rescues the defects in DNA
      methylation, histone H3K9 dimethylation, and chromatin silencing. The competitive
      inhibitor of methyltransferases, S-adenosylhomocysteine, is markedly upregulated
      in fpgs1, by which fpgs1 reduces S-adenosylmethionine accessibility to
      methyltransferases and accordingly affects DNA and histone methylation. These
      results suggest that FPGS1-mediated folate polyglutamylation is required for DNA
      methylation and H3K9 dimethylation through its function in one-carbon metabolism.
      Our study makes an important contribution to understanding the complex interplay
      among metabolism, development, and epigenetic regulation. 

PMID- 23881412
TI  - Biogenesis, turnover, and mode of action of plant microRNAs.
AB  - MicroRNAs (miRNAs) are small RNAs that control gene expression through silencing
      of target mRNAs. Mature miRNAs are processed from primary miRNA transcripts by
      the endonuclease activity of the DICER-LIKE1 (DCL1) protein complex. Mechanisms
      exist that allow the DCL1 complex to precisely excise the miRNA from its
      precursor. Our understanding of miRNA biogenesis, particularly its intersection
      with transcription and other aspects of RNA metabolism such as splicing, is still
      evolving. Mature miRNAs are incorporated into an ARGONAUTE (AGO) effector complex
      competent for target gene silencing but are also subjected to turnover through a
      degradation mechanism that is beginning to be understood. The mechanisms of miRNA
      target silencing in plants are no longer limited to AGO-catalyzed slicing, and
      the contribution of translational inhibition is increasingly appreciated. Here,
      we review the mechanisms underlying the biogenesis, turnover, and activities of
      plant miRNAs. 

PMID- 23881415
TI  - Functional neuroprotection and efficient regulation of GDNF using destabilizing
      domains in a rodent model of Parkinson's disease.
AB  - Glial cell line-derived neurotrophic factor (GDNF) has great potential to treat
      Parkinson's disease (PD). However, constitutive expression of GDNF can over time
      lead to side effects. Therefore, it would be useful to regulate GDNF expression.
      Recently, a new gene inducible system using destabilizing domains (DD) from E.
      coli dihydrofolate reductase (DHFR) has been developed and characterized. The
      advantage of this novel DD is that it is regulated by trimethoprim (TMP), a well
      characterized drug that crosses the blood-brain barrier and can therefore be used
      to regulate gene expression in the brain. We have adapted this system to regulate
      expression of GDNF. A C-terminal fusion of GDNF and a DD with an additional furin
      cleavage site was able to be efficiently regulated in vitro, properly processed
      and was able to bind to canonical GDNF receptors, inducing a signaling cascade
      response in target cells. In vivo characterization of the protein showed that it
      could be efficiently induced by TMP and it was only functional when gene
      expression was turned on. Further characterization in a rodent model of PD showed
      that the regulated GDNF protected neurons, improved motor behavior of animals and
      was efficiently regulated in a pathological setting.

PMID- 23881416
TI  - Elevated cerebral cortical CD24 levels in patients and mice with traumatic brain
      injury: a potential negative role in nuclear factor kappab/inflammatory factor
      pathway.
AB  - Increasing evidence indicates that sterile inflammatory response contributes to
      secondary brain injury following traumatic brain injury (TBI). However, the
      specific mechanisms remain largely unknown, as is whether CD24, known as an
      important regulator in the non-infectious inflammatory response, plays a role in
      secondary brain injury after TBI. Here, the expression of CD24 was detected in
      samples from patients with TBI by quantitative real-time polymerase chain
      reaction (PCR), western blotting, immunohistochemistry and immunofluorescence.
      RNA interference was used to investigate the effects of CD24 on inflammatory
      response in a mouse model of TBI. Nuclear factor kappa B (NF-kappaB) DNA-binding
      activity was measured by electrophoretic mobility shift assay, and the levels of
      downstream pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and
      Interleukin 1beta (IL-1beta) were detected by real-time PCR. The results
      indicated that both the mRNA and protein levels of CD24 were markedly elevated
      after TBI in humans and mice, showing a time-dependent expression. The expression
      of CD24 could be observed in neurons, astrocytes and microglia in both humans and
      mice. Meanwhile, downregulation of CD24 significantly induced an increase of NF
      kappaB DNA-binding activity and mRNA levels of TNF-alpha and IL-1beta. These
      findings indicated that CD24 expression could negatively regulate the NF
      kappaB/inflammatory factor pathway after experimental TBI in mice, thus providing
      a novel target for therapeutic intervention of TBI. 

PMID- 23881417
TI  - The relationship between the area of peripherally-derived pressure volume loops
      and systemic vascular resistance.
AB  - Arterial and photoplethysmographic (PPG) waveforms have been utilized to non
      invasively estimate stroke volume from the pulse contour. The ability of these
      pulse contour devices to accurately predict stroke volume is degraded when
      afterload changes significantly. There is a need for a non-invasive device
      capable of identifying when vascular tone has changed. Shelley et al. previously
      described a qualitative relationship between peripheral pressure volume (PV)
      loops (in which pressure waveforms from an intra-arterial catheter are combined
      with volume waveforms from the PPG waveform) and changes in vascular tone. The
      purpose of this study was to quantitatively compare changes in the area of
      peripheral PV loops with changes in systemic vascular resistance (SVR) in a
      patient population undergoing major surgery. Physiologic data from ten patients
      undergoing liver transplantation was extracted from a hemodynamic database. A
      peak detection algorithm was applied to both the arterial and PPG waveforms,
      which were manually aligned so that the troughs occurred at identical time
      points. PV loop area (PVA) for each heartbeat was calculated and median PVA was
      recorded for each minute. PVA for each patient was indexed to the average value
      for the first 5 min (because PPG amplitude has no standard and is not comparable
      between patients) and compared to indexed SVR at all points for which SVR was
      available. SVR and PVA were plotted as a function of time and outliers (3.1 %)
      removed. The Pearson correlation coefficient describing the relationship between
      PVAi and SVRi was 0.67 (1,728 min of data, p = 0.0020, sign test over 10
      patients) and between MAP and SVR was 0.71. There was no meaningful correlation
      between DeltaSVR and either DeltaPVA or DeltaMAP (based on minute-to-minute
      changes). Indexed values of PVA are correlated with indexed values of SVR and may
      serve as a useful monitor for changes in afterload but in their present form do
      not offer added value above the measurement of MAP. Incorporation of different
      (e.g. finger, forehead) and redundant (e.g. bilateral) sites may significantly
      improve the accuracy of this technique. 

PMID- 23881418
TI  - A pilot study quantifying the shape of tidal breathing waveforms using centroids
      in health and COPD.
AB  - During resting tidal breathing the shape of the expiratory airflow waveform
      differs with age and respiratory disease. While most studies quantifying these
      changes report time or volume specific metrics, few have concentrated on waveform
      shape or area parameters. The aim of this study was to derive and compare the
      centroid co-ordinates (the geometric centre) of inspiratory and expiratory flow
      time and flow-volume waveforms collected from participants with or without COPD.
      The study does not aim to test the diagnostic potential of these metrics as an
      age matched control group would be required. Twenty-four participants with COPD
      and thirteen healthy participants who underwent spirometry had their resting
      tidal breathing recorded. The flow-time data was analysed using a Monte Carlo
      simulation to derive the inspiratory and expiratory flow-time and flow-volume
      centroid for each breath. A comparison of airflow waveforms show that in COPD,
      the breathing rate is faster (17 +/- 4 vs 14 +/- 3 min(-1)) and the time to reach
      peak expiratory flow shorter (0.6 +/- 0.2 and 1.0 +/- 0.4 s). The expiratory flow
      time and flow-volume centroid is left-shifted with the increasing asymmetry of
      the expired airflow pattern induced by airway obstruction. This study shows that
      the degree of skew in expiratory airflow waveforms can be quantified using
      centroids.

PMID- 23881419
TI  - A new experimental system for simultaneous application of cyclic tensile strain
      and fluid shear stress to tenocytes in vitro.
AB  - Tenocyte mechanotransduction has been of great interest to researchers in tendon
      mechanobiology and biomechanics. In vivo, tenocytes are subjected to tensile
      strain and fluid shear stress, but most studies of tenocyte mechanobiology have
      been to understand how tenocytes regulate their functions in response to tensile
      strain. Thus, there is still much to know about tenocyte responses to fluid shear
      stress, partly due to the difficulty of devising a suitable experimental set-up
      and understanding the exact magnitude of imposed fluid shear stress. Therefore,
      this study was performed to test a new experimental system, which is suitable for
      the application of tensile strain and fluid shear stress to tenocytes in vitro.
      It was experimentally and numerically confirmed that tenocytes could maintain
      their in situ morphology within microfabricated microgrooves; also, physiological
      tensile strain and a wide range of fluid shear stress magnitudes can be applied
      to these cells. Indeed, it was demonstrated that the combined stimulation of
      cyclic tensile strain and oscillatory fluid shear stress induced a greater
      synergetic effect on tenocyte calcium response and significantly increased the
      percentage of tenocyte exhibiting increases in intracellular Ca(2+) concentration
      compared to the solo applications of these two modes of mechanical stimulation.
      The experimental system presented here is suitable for research of tenocyte
      mechanobiology, particularly mechanotransduction events, which were difficult to
      study using previous experimental models like explants and cell monolayers. 

PMID- 23881420
TI  - Supplemental issue on does early intervention prevent health-risking sexual
      behaviors related to HIV/AIDS: commentary on effects.

PMID- 23881421
TI  - The effect of grape seed extract on the pharmacokinetics of dextromethorphan in
      healthy volunteers.
AB  - PURPOSE: Grape seed extract (GSE) has been shown to inhibit the cytochrome P450
      (CYP) 2D6 isoenzyme in vitro. To determine the clinical effect of GSE on CYP2D6,
      the pharmacokinetic interaction between GSE and the sensitive CYP2D6 probe
      dextromethorphan in healthy adult volunteers was examined. METHODS: In this open
      label, randomized, cross-over study, 30 subjects were assigned to cohort A or B.
      Both cohorts ingested 30 mg dextromethorphan hydrobromide on day 1 and day 10.
      Cohort A received 100 mg GSE capsules three times daily on days 8, 9 and 10,
      while cohort B started with GSE on day -1 until day 1. After urine collection (0
      8 h) on day 1 and day 10, the urinary dextromethorphan to dextrorphan metabolic
      ratio was determined. RESULTS: Among 28 evaluable subjects, an increase of the
      urinary metabolic ratio was observed in 16 subjects (57 %). The mean metabolic
      ratio (+/- standard deviation) before and after GSE supplementation was 0.41 (+/-
      0.56) and 0.48 (+/- 0.59), respectively. This result was neither statistically (P
      = 0.342) nor clinically [geometric mean ratio 1.10, 90 % CI (0.93-1.30)]
      significant. Further, the majority (73 %) of the included subjects did not
      experience any adverse events after intake of dextromethorphan or GSE.
      CONCLUSIONS: Supplementation of GSE did not significantly affect the urinary
      dextromethorphan to dextrorphan metabolic ratio in healthy volunteers. The
      results of this clinical study indicate that GSE appears to be safe to combine
      with drugs extensively metabolized by CYP2D6, such as dextromethorphan and
      tamoxifen.

PMID- 23881423
TI  - US and MRI findings of fetal dural sinus thrombosis: report of two cases.

PMID- 23881422
TI  - Ventriculoperitoneal shunt as a primary neurosurgical procedure in newborn
      posthemorrhagic hydrocephalus: report of a series of 47 shunted patients.
AB  - PURPOSE: Intraventricular hemorrhage is the most common cause of infantile
      acquired hydrocephalus. Our objective is to determine if the implantation of
      ventriculoperitoneal shunt in posthemorrhagic hydrocephalus as a primary and
      definitive neurosurgical treatment, with no previous temporary procedures, would
      decrease complication rates with good functional outcomes. METHODS: Two hundred
      seventy-one patients with germinal matrix hemorrhage were diagnosed at the Carlos
      Haya Hospital between 2003 and 2010. Forty-seven patients underwent
      ventriculoperitoneal shunt after developing symptomatic hydrocephalus. The
      minimum weight required for shunt implantation was 1,500 g. We recorded
      complications related to the surgical procedure and analyzed functional state
      with a self-developed four-grade scale. RESULTS: One hundred thirty-nine (51.3 %)
      patients with intraventricular hemorrhage developed ventricular dilatation, but
      only 47 patients (17.34 %) needed shunting. In seven cases, temporary
      neurosurgical procedures were performed, but in all of them, this was followed by
      ventriculoperitoneal shunt implantation. The infection rate was 4.25 %, and shunt
      obstruction rate was 4.25 %. More than 80 % of patients were classified as good
      or excellent functional state. Mean follow-up period was 38.75 months (SD, 27.09;
      range, 1-102 months). CONCLUSIONS: Ventriculoperitoneal shunting as a primary
      neurosurgical treatment in posthemorrhagic hydrocephalus would decrease surgical
      morbidity with good functional outcome.

PMID- 23881424
TI  - Computational fluid dynamics of ventricular catheters used for the treatment of
      hydrocephalus: a 3D analysis.
AB  - INTRODUCTION: The most common treatment for hydrocephalus remains the
      ventriculoperitoneal shunt. Yet, the most frequent complication is ventricular
      catheter obstruction, which may account for 50-80 % of newly inserted shunts.
      Although many factors contribute to this, the main one is related to flow
      characteristics of the catheter within the hydrocephalic brain. A landmark study
      by Lin et al. addressed the problem of fluid characteristics in ventricular
      catheters using a two-dimensional simulation program of computational fluid
      dynamics (CFD). METHODS: The authors have studied five current commercially
      available ventricular catheter designs using CFD in three-dimensional automated
      designs. The general procedure for the development of a CFD model involves
      incorporating the physical dimensions of the system to be studied into a virtual
      wire-frame model. The shape and features of the actual physical model are
      transformed into coordinates for the virtual space of the computer and a CFD
      computational grid (mesh) is generated. The fluid properties and motion are
      calculated at each of these grid points. After grid generation, flow field
      boundary conditions are applied, and the fluid's thermodynamic and transport
      properties are included. At the end, a system of strongly coupled, nonlinear,
      partial differential conservation equations governing the motion of the flow
      field are numerically solved. This numerical solution describes the fluid motion
      and properties. RESULTS: The authors calculated that most of the total fluid mass
      flows into the catheter's most proximal holes. Fifty to 75 % flows into the two
      most proximal sets of inlets of current commercially available 12-32-hole
      catheters. Some flow uniformity was disclosed in Rivulet-type catheter.
      CONCLUSIONS: Most commercially available ventricular catheters have an abnormally
      increase flow distribution pattern. New catheter designs with variable hole
      diameters along the catheter tip will allow the fluid to enter the catheter more
      uniformly along its length, thereby reducing the probability of its becoming
      occluded.

PMID- 23881426
TI  - "Rabbit ear" scalp deformity caused by massive subdural effusion in infant
      following bilateral bur-hole drainage failure: successfully managed with subduro
      peritoneal shunt.
AB  - INTRODUCTION: Subdural effusion in an infant is a rare clinical scenario which
      may be secondary to a variety of etiologies. Massive subdural effusion is an
      extremely rare complication of head injury. CASE REPORT: Authors report a rare
      case of progressive massive subdural effusion which, despite bilateral bur-hole
      placement and drainage, failed and presented with visual deterioration and
      massive bulge of the scalp at bur-hole sites, producing a rabbit ear appearance
      in a 10-month-old infant. Ultimately, cystoperitoneal shunt was carried out in a
      desperate attempt to prevent impending rupture of scalp sutures at sites of
      previous bur-hole placement. This was followed by not only complete resolution of
      hygroma but also visual recovery. The patient is doing well at 6 months following
      shunt, regaining normal vision and appropriate developmental milestones. A MRI
      scan of the brain was carried out at last follow-up, which revealed mild
      ventriculomegaly with the rest of the brain being unremarkable, and subduro
      peritoneal shunt in situ. Such a case has not been reported in the literature
      till date. DISCUSSION: Subdural effusion usually runs a self-limiting course.
      Though neurosurgical intervention is occasionally needed, different methods of
      surgical procedure for management include bur hole alone, bur holes with subdural
      drain placement, twist drill craniotomy with drain, and even craniotomy. Various
      methods of management are discussed along with a review of pertinent literature.

PMID- 23881425
TI  - Clinical outcomes of temporary shunting for infants with cerebral
      pseudomeningocele.
AB  - OBJECTIVE: Although in the case of subdural collections temporary shunting has
      been suggested as a viable alternative for definitive drainage of the accumulated
      fluid until restoration of the normal CSF dynamics, there is no agreement on the
      best management strategy for pseudomeningocele. METHODS: The authors performed a
      retrospective chart review in order to evaluate the clinical outcomes of infants
      temporarily shunted for pseudomeningocele without encephalocele at our
      institution (The University of Illinois at Peoria/Illinois Neurological
      Institute) in the period from 2004 to 2012. The epidemiological characteristics,
      clinical management, and final outcomes of such subpopulation were compared with
      a control group which received temporary shunting for subdural hematomas (SDH)
      during the same period. RESULTS: Four patients (100% male) ranging in age from
      8.9 to 27.1 months (mean = 13.88) with pseudomeningocele and 17 patients (64.7%
      male) ranging in age from 1.9 to 11.8 months (mean = 4.15) with SDH were
      identified. Although the initial management included sequential percutaneous
      subdural tapping in 82% of the patients, all children ultimately failed such
      strategy, requiring either subdural-peritoneal (81% of the cases) or subgaleal
      peritoneal (19% of the cases) shunting. The mean implant duration was 201 days
      for the pseudomeningocele group and 384 days for the SDH one. Mean post-shunt
      hospitalization was 2 days for patients with pseudomeningocele and 4 days for
      patients with SDH. There was no statistical difference in terms of complications,
      length of hospitalization post-shunting, or clinical outcomes between the
      patients with pseudomeningocele and those with SDH. CONCLUSIONS: Temporary
      shunting of infants with pseudo-meningocele constitutes a viable therapeutic
      alternative with favorable clinical outcomes and a low risk of shunt dependency
      similar to those of children with SDH.

PMID- 23881427
TI  - Extending survival with the use of targeted therapy in the treatment of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with an
      increasing incidence projected through 2020. HCC is the third-leading cause of
      cancer-related deaths worldwide. Management of HCC is complicated by the fact
      that these patients also have a cirrhotic or otherwise diseased liver that led to
      the tumorigenesis. To aid in treatment decisions, several staging systems have
      been developed. In the United States, the Barcelona Clinic Liver Cancer (BCLC)
      system has emerged as the predominant system, owing to its concomitant
      consideration of tumor stage, liver function, and physical status, as well as its
      ability to identify patients with early-stage disease who may benefit from
      curative therapies. Surveillance for HCC has gained increasing importance in
      light of several studies demonstrating both clinical and cost benefits. Once HCC
      is detected and diagnosed, it is usually managed according to its BCLC stage.
      Patients with early-stage disease often benefit from potentially curative
      therapies, such as surgical resection and liver transplantation. Often, local
      ablation such as radiofrequency ablation or percutaneous alcohol injection can be
      used not only as an effective treatment, but also as a bridge therapy to maintain
      the status of patients on the liver transplant list. Intermediate-stage patients
      are typically treated with transarterial chemoembolization, but have a high rate
      of disease recurrence. The multikinase inhibitor sorafenib is the only treatment
      option approved for patients with advanced-stage HCC. Sorafenib has demonstrated
      a significant survival advantage in these patients. Numerous studies have
      evaluated other novel targeted therapies in this setting, but none have shown
      superiority to sorafenib. 

PMID- 23881431
TI  - Implementation of integrated mismatch negativity in differentiating children with
      specific language impairment.
AB  - OBJECTIVE: The study aimed to assess the use of Integrated Mismatch Negativity
      (MMNi) in differentiating children with specific language impairment (SLI) from a
      control group. DESIGN: Six conditions were created using a 1,000-Hz standard
      stimulus with three deviants of 1,020, 1,050, or 1,100 Hz and two interstimulus
      intervals of 400 and 200 ms. Recordings were processed offline using NeuroScan
      Edit (NeuroScan, Texas, United States). Four time analysis points were chosen and
      the magnitude of the integrated deviant was compared with the 100 standard
      subaverages. Mismatch negativity (MMN) presence was determined when 10 or less of
      the standard subaverages were less than the deviant subaverage magnitude. STUDY
      PARTICIPANTS: A total of 18 children with SLI and 35 typical development children
      participated in the study. RESULTS: Pearson chi-square test demonstrated that the
      proportion of MMN presence in the SLI group was not significantly different from
      the control group and it did not vary with condition. Two-way between-group
      analysis of variance confirmed that using 1,000 Hz standard, 1,050 Hz deviant,
      and 400 ms interstimulus interval was significantly different from the other
      conditions. CONCLUSION: MMNi does not serve as a tool for identifying children
      with SLI when using pure-tone stimuli. However, using different time analysis
      points with MMNi should be explored further, particularly with speech material.

PMID- 23881432
TI  - Adding Saxagliptin to Metformin Extended Release (XR) or Uptitration of Metformin
      XR: Efficacy on Daily Glucose Measures.
AB  - INTRODUCTION: Saxagliptin added to metformin extended release (XR) and uptitrated
      metformin XR were evaluated for their impact on daily glucose measurements and
      their tolerability in patients with type 2 diabetes mellitus (T2DM) inadequately
      controlled with metformin monotherapy. METHODS: Patients aged 18-78 years on
      metformin 850-1,500 mg with glycated hemoglobin (HbA1c) 7.5-11.5% at screening
      were eligible for this double-blind, active-controlled study. Patients were
      stabilized on metformin XR 1,500 mg before randomization. Patients with HbA1c 7
      11% and fasting plasma glucose (FPG) >=126 mg/dL after a 4- 8-week lead-in period
      were randomly assigned to saxagliptin 5 mg + metformin XR 1,500 mg or metformin
      XR 500 mg + metformin XR 1,500 mg (uptitrated metformin XR). The primary end
      point was change from baseline to week 4 in 24-h mean weighted glucose (MWG).
      Secondary end points were changes from baseline to week 4 in 2-h postprandial
      glucose (PPG) and FPG. RESULTS: At week 4, the adjusted mean +/- SE change from
      baseline in 24-h MWG was -19.0 +/- 5.7 mg/dL (95% CI -30.3 to -7.6) for
      saxagliptin + metformin XR and -8.2 +/- 6.0 mg/dL (95% CI -20.0 to 3.7) for
      uptitrated metformin XR. Mean changes from baseline in 2-h PPG and FPG were
      numerically greater with saxagliptin + metformin XR versus uptitrated metformin
      XR. The incidence of adverse events was lower with saxagliptin + metformin XR
      (17.4%) versus uptitrated metformin XR (31.9%) mainly due to differences in
      gastrointestinal adverse event incidence (2.2% vs 10.6%, respectively). There
      were no reports of confirmed hypoglycemia in either group. CONCLUSION: In this 4
      week study in patients with T2DM inadequately controlled with metformin
      monotherapy, saxagliptin added to metformin XR demonstrated a trend for
      improvement in measures of daily glycemic control, with fewer gastrointestinal
      adverse events, compared with uptitrated metformin.

PMID- 23881433
TI  - Transfer effects of fall training on balance performance and spatiotemporal gait
      parameters in healthy community-dwelling older adults: a pilot study.
AB  - This study examined transfer effects of fall training on fear of falling (Falls
      Efficacy Scale-International [FES-I]), balance performance, and spatiotemporal
      gait characteristics in older adults. Eighteen community-dwelling older adults
      (ages 65-85) were randomly assigned to an intervention or control group. The
      intervention group completed 12 training sessions (60 min, 6 weeks). During pre-
      and posttesting, we measured FES-I, balance performance (double limb, closed
      eyes; single limb, open eyes; double limb, open eyes with motor-interfered task),
      and gait parameters (e.g., velocity; cadence; stride time, stride width, and
      stride length; variability of stride time and stride length) under single- and
      motor-interfered tasks. Dual tasks were applied to appraise improvements of
      cognitive processing during balance and gait. FES-I (p = .33) and postural sway
      did not significantly change (0.36 < p < .79). Trends toward significant
      interaction effects were found for step width during normal walking and stride
      length variability during the motor dual task (p = .05, etap 2 = .22). Fall
      training did not sufficiently improve fear of falling, balance, or gait
      performance under single- or dual-task conditions in healthy older adults.

PMID- 23881434
TI  - Large aneurysm in saphenous vein coronary artery graft with fistula: case report
      and review.
AB  - Aneurysms developing in a saphenous vein graft (SVG) after coronary artery bypass
      grafting (CABG) are an unusual complication and fistulae forming between an SVG
      aneurysm and a cardiac chamber are even rarer. A 71-year-old man had undergone a
      triple CABG with the left internal thoracic artery and double SVGs. Twenty years
      later, he was admitted with repeated congestive heart failure. A large true
      aneurysm (99 * 60 mm) developed in the mid portion of a saphenous vein graft to
      the right coronary artery together with a fistula with a diameter of 8 mm in the
      right atrium. The aneurysm was surgically resected and the fistula was closed.

PMID- 23881435
TI  - Abstracts of the 7th Congress of the African League of Associations for
      Rheumatology (AFLAR) and the 23rd Congress of the South African Rheumatism and
      Arthritis Association (SARAA). April 3-6, 2013. Durban, South Africa.

PMID- 23881436
TI  - A meta-analysis of alcohol consumption and the risk of gout.
AB  - Alcohol consumption had been linked to the risk of gout theoretically, but the
      results from observational studies were conflicting. Hence, a meta-analysis was
      conducted to assess the effect of alcohol consumption on the risk of gout. A
      comprehensive search was performed to identify all eligible studies on the
      association of alcohol consumption with gout risk. Pooled relative risks (RRs)
      with 95 % confidence intervals (CIs) from fixed and random effects models were
      calculated. A total of 12 articles with 17 studies involving 42,924 cases met the
      inclusion criteria. The pooled RR for highest vs. non/occasional alcohol drinking
      in every study was 1.98 (95 % CI, 1.52-2.58). The RRs for light (<=1 drink/day),
      moderate (>1 to <3 drinks/day), and heavy drinking (>=3 drinks/day) vs.
      non/occasional alcohol drinking were 1.16 (95 % CI, 1.07-1.25), 1.58 (95 % CI,
      1.50-1.66), and 2.64 (95 % CI, 2.26-3.09), respectively. The results suggested
      that alcohol consumption might be associated with increased risk of gout.

PMID- 23881437
TI  - Translation, cross-cultural adaptation, and validation of the Mouth Handicap in
      Systemic Sclerosis questionnaire (MHISS) into the Dutch language.
AB  - The Mouth Handicap in Systemic Sclerosis (MHISS) is a French-generic
      questionnaire evaluating mouth-opening restriction, dryness, and esthetic
      concerns. The aim of this study was to translate and adapt the MHISS
      questionnaire into the Dutch language and evaluate its psychometric properties.
      The MHISS was translated according to international guidelines, field-tested
      among 16 systemic sclerosis (SSc) patients, and adapted. Subsequently, the Dutch
      MHISS was administered to 52 SSc patients visiting the outpatient or day patient
      clinic of a university hospital and readministered after 2 weeks. Internal
      consistency was tested by computing Cronbach's alpha. Test-retest reliability was
      determined by computing the intraclass correlation coefficient (ICC) and validity
      by determining associations with measures of overall functioning (Health
      Assessment Questionnaire (HAQ)), maximum mouth opening (MMO, in millimeter),
      subjective xerostomia (visual analog scale), and objective xerostomia (Saxon
      test). Patients had mean +/- standard deviation (SD) age and disease duration of
      55 +/- 21 and 7.2 +/- 7.3 years. Twenty-seven (52 %) patients had diffuse
      cutaneous SSc. The mean Dutch MHISS score was 17.5 (SD 10.0) with Cronbach's
      alpha being 0.862. Dutch MHISS scores differed significantly between patients
      with high and low disability levels (HAQ, MMO, and subjective and objective
      xerostomia divided according to the median; paired t test). Spearman rank
      correlations with HAQ (r = 0.599, p = 0.000), MMO (r = -0.518, p = 0.000), and
      subjective xerostomia (r = 0.536, p = 0.000) were moderate; correlation with
      objective xerostomia did not reach statistical significance. The ICC was 0.94.
      The Dutch version of the MHISS demonstrated good psychometric properties and is
      useful in assessing mouth disability in SSc patients.

PMID- 23881438
TI  - The relationship between disease activity and depressive symptoms severity and
      optimism--results from the IMPROVED study.
AB  - To assess depressive symptoms severity and dispositional optimism in patients
      with recent onset arthritis both before and after 4 months treatment. Two hundred
      twenty-two patients with recent onset RA and undifferentiated arthritis in the
      IMPROVED study filled out the Beck Depression Inventory (BDI-II) to assess
      depressive symptoms severity and the Life Orientation Test Revised (LOT-R) to
      measure optimism before and after 4 months of treatment. All patients were
      treated with methotrexate 25 mg/week and prednisone 60 mg/day (tapered to 7.5
      mg/day in 7 weeks). Linear regression analysis was used to assess the association
      between the disease activity score (DAS) and its components (tender joint count,
      general well-being measured with a visual analogue scale (VAS), swollen joint
      count, and erythrocyte sedimentation rate) with the BDI-II an LOT-R scores. In
      general, depressive symptoms were mild. The DAS was an independent predictor of
      depressive symptoms scores both at baseline and after 4 months follow-up, in
      particular tender joint count and VAS global health. Disease activity was not
      associated with the level of optimism. Nevertheless, patients who achieved
      clinical remission improved significantly more in both depression score and
      optimism score than patients who did not. Patients with early arthritis report
      improvement in depressive symptoms and optimism with improvement in disease
      activity and achieving clinical remission. Depression scores are associated with
      pain and unwell being but not with swollen joint counts and inflammatory
      parameters.

PMID- 23881440
TI  - Association between interleukin 6 and interleukin 16 gene polymorphisms and
      coronary heart disease risk in a Chinese population.
AB  - OBJECTIVE: To investigate the role of interleukin 6 (IL6) and IL16 single
      nucleotide polymorphisms (SNPs) in coronary artery disease (CAD) risk in a
      Chinese population. METHODS: Patients with CAD and healthy control subjects were
      recruited. IL6 (rs1800795 and rs1800796) and IL16 (rs8034928, rs3848180,
      rs4577037, rs1131445, rs4778889 and rs11556218) genotyping was performed on the
      MassARRAY(r) platform (Sequenom(r), San Diego, CA, USA). RESULTS: Frequencies of
      rs8034928 variant C allele and rs11556218 variant T allele were higher in
      patients with CAD (n = 326) than controls (n = 341). The rs8034928 C/C genotype
      (odds ratio [OR] 2.03; 95% confidence intervals [CI] 1.16, 3.62) and C allele (OR
      1.97; 95%CI 1.15, 3.45) were associated with increased risk of CAD compared with
      wild type. Similarly, the rs11556218 T/T genotype (OR 2.44; 95%CI 1.15, 5.44) and
      T allele (OR 2.37; 95%CI 1.13, 5.24) were associated with increased CAD risk
      compared with wild type. CONCLUSION: The SNPs rs8034928 and rs11556218 are
      associated with CAD risk in the Chinese population, and may be useful predictive
      markers for CAD susceptibility.

PMID- 23881439
TI  - Alendronate treatment for hip osteoarthritis: prospective randomized 2-year
      trial.
AB  - We examined the clinical efficacy of alendronate treatment for hip osteoarthritis
      using multiple outcome measures. Fifty patients with symptomatic hip
      osteoarthritis were enrolled in this prospective trial. The patients were
      randomly assigned to an alendronate group (35 mg/week alendronate and 600 mg/day
      calcium lactate) or a control group (600 mg/day calcium lactate) for 2 years. The
      groups were compared with regard to the following five parameters. The primary
      outcome measures are the following: (1) the Western Ontario and McMaster
      Universities (WOMAC) osteoarthritis pain score and the visual analog score (VAS).
      The secondary outcome measures are the following: (2) joint space width (JSW)
      measured on radiographs using a semiautomatic computer software, (3) the
      biochemical markers urinary N-telopeptide of type I collagen (NTX-I) and C
      terminal cross-linking telopeptide of type II collagen (CTX-II), (4) dual-energy
      X-ray absorptiometry of the hip and lumbar spine, and (5) bone marrow edema on
      magnetic resonance images. The alendronate group showed pain improvement trends
      in VAS and WOMAC scores, whereas the control group showed worsening of pain. The
      alendronate group showed significant improvement in WOMAC pain scores after 12
      months (p = 0.031) but no significant prevention of structural osteoarthritis
      progression, defined as a decrease in JSW >0.30 mm or conversion to total hip
      arthroplasty. There was significantly larger decrease in the biochemical markers
      and significantly increased bone density in the alendronate group. Alendronate
      treatment by standard dose for osteoporosis showed clinical efficacy for
      decreasing pain but failed to show preventive effects for structural progression
      of hip osteoarthritis.

PMID- 23881441
TI  - New synthesis: investigating mutualisms in virus-vector interactions.

PMID- 23881442
TI  - Dynamic chemical communication between plants and bacteria through airborne
      signals: induced resistance by bacterial volatiles.
AB  - Certain plant growth-promoting rhizobacteria (PGPR) elicit induced systemic
      resistance (ISR) and plant growth promotion in the absence of physical contact
      with plants via volatile organic compound (VOC) emissions. In this article, we
      review the recent progess made by research into the interactions between PGPR
      VOCs and plants, focusing on VOC emission by PGPR strains in plants. Particular
      attention is given to the mechanisms by which these bacterial VOCs elicit ISR. We
      provide an overview of recent progress in the elucidation of PGPR VOC
      interactions from studies utilizing transcriptome, metabolome, and proteome
      analyses. By monitoring defense gene expression patterns, performing 2
      dimensional electrophoresis, and studying defense signaling null mutants,
      salicylic acid and ethylene have been found to be key players in plant signaling
      pathways involved in the ISR response. Bacterial VOCs also confer induced
      systemic tolerance to abiotic stresses, such as drought and heavy metals. A
      review of current analytical approaches for PGPR volatile profiling is also
      provided with needed future developments emphasized. To assess potential
      utilization of PGPR VOCs for crop plants, volatile suspensions have been applied
      to pepper and cucumber roots and found to be effective at protecting plants
      against plant pathogens and insect pests in the field. Taken together, these
      studies provide further insight into the biological and ecological potential of
      PGPR VOCs for enhancing plant self-immunity and/or adaptation to biotic and
      abiotic stresses in modern agriculture. 

PMID- 23881443
TI  - Imaging mass spectrometry of a coral microbe interaction with fungi.
AB  - Fungal infections are increasing worldwide, including in the aquatic environment.
      Microbiota that coexist with marine life can provide protection against fungal
      infections by secretion of metabolites with antifungal properties. Our laboratory
      has developed mass spectrometric methodologies with the goal of improving our
      functional understanding of microbial metabolites and guiding the discovery
      process of anti-infective agents from natural sources. GA40, a Bacillus
      amyloliquefaciens strain isolated from an octocoral in Panama, displayed
      antifungal activity against various terrestrial and marine fungal strains. Using
      matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI
      IMS), the molecular species produced by this microbe were visualized in a side-by
      side interaction with two representative fungal strains, Aspergillus fumigatus
      and Aspergillus niger. The visualization was performed directly on the agar
      without the need for extraction. By evaluating the spatial distributions,
      relative intensities and m/z values of GA40 secreted metabolites in the fungal
      interactions and singly grown control colonies, we obtained insight into the
      antifungal activity of secreted metabolites. Annotation of GA40 metabolites
      observed in MALDI-IMS was facilitated by MS/MS networking analysis, a mass
      spectrometric technique that clusters metabolites with similar MS/MS
      fragmentation patterns. This analysis established that the predominant GA40
      metabolites belong to the iturin family. In a fungal inhibition assay of A.
      fumigatus, the GA40 iturin metabolites were found to be responsible for the
      antifungal properties of this Bacillus strain. 

PMID- 23881444
TI  - Combining mutualistic yeast and pathogenic virus--a novel method for codling moth
      control.
AB  - The combination of a pathogenic virus and mutualistic yeasts isolated from larvae
      of codling moth Cydia pomonella is proposed as a novel insect control technique.
      Apples were treated with codling moth granulovirus (CpGV) and either one of three
      yeasts, Metschnikowia pulcherrima, Cryptococcus tephrensis, or Aureobasidium
      pullulans. The combination of yeasts with CpGV significantly increased mortality
      of neonate codling moth larvae, compared with CpGV alone. The three yeasts were
      equally efficient in enhancing the activity of CpGV. The addition of brown cane
      sugar to yeast further increased larval mortality and the protection of fruit
      against larvae. In comparison, without yeast, the addition of sugar to CpGV did
      not produce a significant effect. A field trial confirmed that fruit injury and
      larval survival were significantly reduced when apple trees were sprayed with
      CpGV, M. pulcherrima, and sugar. We have shown earlier that mutualistic yeasts
      are an essential part of codling moth larval diet. The finding that yeast also
      enhances larval ingestion of an insect-pathogenic virus is an opportunity for the
      development of a novel plant protection technique. We expect the combination of
      yeasts and insect pathogens to essentially contribute to future insect
      management. 

PMID- 23881445
TI  - Functional characterization of the bacterial iac genes for degradation of the
      plant hormone indole-3-acetic acid.
AB  - Pseudomonas putida 1290 is a model organism for the study of bacterial
      degradation of the plant hormone indole-3-acetic acid (IAA). This property is
      encoded by the iac gene cluster. Insertional inactivation and/or deletion of
      individual iac genes and heterologous expression of the gene cluster in
      Escherichia coli were combined with mass spectrometry to demonstrate that iac
      based degradation of IAA is likely to involve 2-hydroxy-IAA, 3-hydroxy-2-oxo-IAA,
      and catechol as intermediates. The first gene of the cluster, iacA encodes for
      the first step in the pathway, and also can convert indole to indoxyl to produce
      the blue pigment indigo. Transcriptional profiling of iac genes in P. putida 1290
      revealed that they were induced in the presence of IAA. Based on results with an
      iacR knockout, we propose that this gene codes for a repressor of iacA expression
      and that exposure to IAA relieves this repression. Transformation of P. putida
      KT2440 (which cannot degrade IAA) with the iac gene cluster conferred the ability
      to grow on IAA as a sole source of carbon and energy, but not the ability to
      chemotaxi towards IAA. We could show such tactic response for P. putida 1290,
      thus representing the first demonstration of bacterial chemotaxis towards IAA. We
      discuss the ecological significance of our findings, and specifically the
      following question: under what circumstances do bacteria with the ability to
      degrade, recognize, and move towards IAA have a selective advantage? 

PMID- 23881448
TI  - Single versus combined cognitive and physical activity effects on fluid cognitive
      abilities of healthy older adults: a 4-month randomized controlled trial with
      follow-up.
AB  - BACKGROUND: Physical and cognitive activity seems to be an effective strategy by
      which to promote age-sensitive fluid cognitive abilities in older adults. METHOD:
      In this randomized controlled trial, 70 healthy senior citizens (age 60-75) were
      allocated to a physical, cognitive, combined physical plus cognitive, and waiting
      control group. The trial assessed information processing speed, short-term
      memory, spatial relations, concentration, reasoning, and cognitive speed.
      RESULTS: In contrast to the control group, the physical, cognitive, and combined
      training groups enhanced their concentration immediately after intervention. Only
      the physical training group showed improved concentration 3 months later. The
      combined training group displayed improved cognitive speed both immediately and
      three months after intervention. The cognitive training group displayed improved
      cognitive speed 3 months after intervention. CONCLUSIONS: Physical, cognitive,
      and combined physical plus cognitive activity can be seen as cognition-enrichment
      behaviors in healthy older adults that show different rather than equal
      intervention effects.

PMID- 23881449
TI  - Controllable disorder in a hybrid nanoelectronic system: realization of a
      superconducting diode.
AB  - We have studied a hybrid nanoelectronic system which consists of an AlGaAs/GaAs
      two-dimensional electron gas (2DEG) in close proximity (~70 nm) to an Al
      superconducting nanofilm. By tuning the current through the Al film, we can
      change the conductance of the 2DEG and furthermore vary the effective disorder in
      the Al superconducting film in a controllable way. When a high current is
      injected into the film, screening which couples the Al film and the 2DEG results
      in a collapse of anti-symmetric behavior in the current-voltage characteristics,
      V(I) ~ -V(-I), which holds true in a conventional superconductor. Our results may
      open a new avenue of experimentally realizing a superconducting diode. 

PMID- 23881446
TI  - Volatile organic compound mediated interactions at the plant-microbe interface.
AB  - Microorganisms colonize the surfaces of plant roots, leaves, and flowers known as
      the rhizosphere, phyllosphere, and anthosphere. These spheres differ largely in a
      number of factors that may determine the ability of microbes to establish
      themselves and to grow in these habitats. In this article, we focus on volatile
      organic compounds (VOCs) emitted by plants, and we discuss their effects on
      microbial colonizers, with an emphasis on bacteria. We present examples of how
      growth-inhibiting properties and mechanisms of VOCs such as terpenoids, benzenoid
      compounds, aliphatics, and sulfur containing compounds prevent bacterial
      colonization at different spheres, in antagonism with their role as carbon
      sources that support the growth of different bacterial taxa. The notion that VOCs
      represent important factors that define bacterial niches is further supported by
      results for representatives of two bacterial genera that occupy strongly
      diverging niches based on scent emissions of different plant species and organs.
      Bacteria are known to either positively or negatively affect plant fitness and to
      interfere with plant-animal interactions. Thus, bacteria and other microbes may
      select for VOCs, enabling plants to control microbial colonizers on their
      surfaces, thereby promoting the growth of mutualists and preventing the
      establishment of detrimental microbes. 

PMID- 23881450
TI  - The development of regional functional connectivity in preterm infants into early
      childhood.
AB  - INTRODUCTION: Resting state networks are proposed to reflect the neuronal
      connectivity that underlies cognitive processes. Consequently, abnormal behaviour
      of these networks due to disease or altered development may predict poor
      cognitive outcome. To understand how very preterm birth may affect the
      development of resting state connectivity, we followed a cohort of very preterm
      born infants from birth through to 4 years of age using resting state functional
      MRI. METHODS: From a larger longitudinal cohort of infants born very preterm (<32
      weeks gestational age), 36 at birth, 30 at term, 21 two-year and 22 four-year
      resting state fMRI datasets were acquired. Using seed-based connectivity analyses
      with seeds in the anterior cingulate cortex, posterior cingulate cortex, left and
      right motor-hand regions and left and right temporal lobes, we investigated local
      and inter-region connectivity as a function of group and age. RESULTS: We found
      strong local connectivity during the preterm period, which matured into inter
      hemispheric and preliminary default-mode network correlations by 4 years of age.
      This development is comparable to the resting state networks found in term-born
      infants of equivalent age. CONCLUSION: The results of this study suggest that
      differences in developmental trajectory between preterm-born and term-born
      infants are small and, if present, would require a large sample from both
      populations to be detected.

PMID- 23881451
TI  - Intraspinal AAV Injections Immediately Rostral to a Thoracic Spinal Cord Injury
      Site Efficiently Transduces Neurons in Spinal Cord and Brain.
AB  - In the vast majority of studies utilizing adeno-associated virus (AAV) in central
      nervous system applications, including those published with spinal cord injury
      (SCI) models, AAV has been administered at the level of the cell body of neurons
      targeted for genetic modification, resulting in transduction of neurons in the
      vicinity of the injection site. However, as SCI interrupts many axon tracts, it
      may be more beneficial to transduce a diverse pool of supraspinal neurons. We
      determined if descending axons severed by SCI are capable of retrogradely
      transporting AAV to remotely transduce a variety of brain regions. Different AAV
      serotypes encoding the reporter green fluorescent protein (GFP) were injected
      into gray and white matter immediately rostral to a spinal transection site. This
      resulted in the transduction of thousands of neurons within the spinal cord and
      in multiple regions within the brainstem that project to spinal cord. In
      addition, we established that different serotypes had disparate regional
      specificity and that AAV5 transduced the most brain and spinal cord neurons. This
      is the first demonstration that retrograde transport of AAV by axons severed by
      SCI is an effective means to transduce a collection of supraspinal neurons. Thus,
      we identify a novel, minimally invasive means to transduce a variety of neuronal
      populations within both the spinal cord and the brain following SCI. This
      paradigm to broadly distribute viral vectors has the potential to be an important
      component of a combinatorial strategy to promote functional axonal
      regeneration.Molecular Therapy-Nucleic Acids (2013) 2, e108;
      doi:10.1038/mtna.2013.34; published online 23 July 2013. 

PMID- 23881452
TI  - BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient
      Serum and Cerebrospinal Fluid Extracellular Vesicles.
AB  - Development of biofluid-based molecular diagnostic tests for cancer is an
      important step towards tumor characterization and real-time monitoring in a
      minimally invasive fashion. Extracellular vesicles (EVs) are released from tumor
      cells into body fluids and can provide a powerful platform for tumor biomarkers
      because they carry tumor proteins and nucleic acids. Detecting rare point
      mutations in the background of wild-type sequences in biofluids such as blood and
      cerebrospinal fluid (CSF) remains a major challenge. Techniques such as BEAMing
      (beads, emulsion, amplification, magnetics) PCR and droplet digital PCR (ddPCR)
      are substantially more sensitive than many other assays for mutant sequence
      detection. Here, we describe a novel approach that combines biofluid EV RNA and
      BEAMing RT-PCR (EV-BEAMing), as well droplet digital PCR to interrogate mutations
      from glioma tumors. EVs from CSF of patients with glioma were shown to contain
      mutant IDH1 transcripts, and we were able to reliably detect and quantify mutant
      and wild-type IDH1 RNA transcripts in CSF of patients with gliomas. EV-BEAMing
      and EV-ddPCR represent a valuable new strategy for cancer diagnostics, which can
      be applied to a variety of biofluids and neoplasms.Molecular Therapy-Nucleic
      Acids (2013) 2, e109; doi:10.1038/mtna.2013.28; published online 23 July 2013. 

PMID- 23881453
TI  - Novel protective effects of histone deacetylase inhibition on stroke and white
      matter ischemic injury.
AB  - Understanding how epigenetics influences the process and progress of a stroke
      could yield new targets and therapeutics for use in the clinic. Experimental
      evidence suggests that inhibitors of zinc-dependent histone deacetylases can
      protect neurons, axons, and associated glia from the devastating effects of
      oxygen and glucose deprivation. While the specific enzymes involved have yet to
      be clearly identified, there are hints from somewhat selective chemical
      inhibitors and also from the use of specific small hairpin RNAs to transiently
      knockdown protein expression. Neuroprotective mechanisms implicated thus far
      include the upregulation of extracellular glutamate clearance, inhibition of p53
      mediated cell death, and maintenance of mitochondrial integrity. The histone
      deacetylases have distinct cellular and subcellular localizations, and discrete
      substrates. As a number of chemical inhibitors are already in clinical use for
      the treatment of cancer, repurposing for the stroke clinic should be expedited. 

PMID- 23881455
TI  - Antioxidative and anti-inflammatory activities of paeoniflorin and oxypaeoniflora
      on AGEs-induced mesangial cell damage.
AB  - Paeonia suffruticosa, an important traditional herbal medicine, has been reported
      to prevent the pathogenesis of diabetic nephropathy through modulating advanced
      glycation end products-induced inflammatory and oxidative stress responses.
      However, little was known about the protective effect of the two major compounds
      in P. suffruticosa, paeoniflorin and oxypaeoniflora, on advanced glycation end
      products-induced mesangial cell damage. In the present study, we investigated the
      protective activities of paeoniflorin and oxypaeoniflora on advanced glycation
      end product-induced oxidative stress and inflammation in mesangial cells HBZY-1.
      The IC50 values of paeoniflorin and oxypaeoniflora for inhibiting 2,2'-azinobis
      (3-thylbenzothiazoline-6-sulfonic acid) formation were 4.197 * 10-4 M and 1.002 *
      10-4 M, respectively. The pretreatment with paeoniflorin and oxypaeoniflora (10-8
      10-4 M) significantly increased advanced glycation end product-induced
      glutathione peroxidase and catalase activities. In the coculture system of HBZY-1
      and macrophages, paeoniflorin and oxypaeoniflora could inhibit remarkably the
      migration of macrophages. Furthermore, paeniflorin and oxypaeniflora attenuated
      markedly advanced glycation end products-induced inflammation cytokines
      interleukin-6 and monocyte chemoattractant protein-1 levels in ELISA and western
      blot analysis in a dose-dependent manner. Taken together, our data provided the
      reliable evidence that paeniflorin and oxypaeniflora were able to attenuate
      advanced glycation end products-induced oxidative damage and inflammation in
      mesangial cells. Paeniflorin and oxypaeniflora might therefore have a beneficial
      effect in the treatment of diabetic nephropathy. 

PMID- 23881454
TI  - Epigenetic regulation of axon outgrowth and regeneration in CNS injury: the first
      steps forward.
AB  - Inadequate axonal sprouting and lack of regeneration limit functional recovery
      following neurologic injury, such as stroke, brain, and traumatic spinal cord
      injury. Recently, the enhancement of the neuronal regenerative program has led to
      promising improvements in axonal sprouting and regeneration in animal models of
      axonal injury. However, precise knowledge of the essential molecular determinants
      of this regenerative program remains elusive, thus limiting the choice of fully
      effective therapeutic strategies. Given that molecular regulation of axonal
      outgrowth and regeneration requires carefully orchestrated waves of gene
      expression, both temporally and spatially, epigenetic changes may be an ideal
      regulatory mechanism to address this unique need. While recent evidence suggests
      that epigenetic modifications could contribute to the regulation of axonal
      outgrowth and regeneration following axonal injury in models of stroke, and
      spinal cord and optic nerve injury, a number of unanswered questions remain. Such
      questions require systematic investigation of the epigenetic landscape between
      regenerative and non-regenerative conditions for the potential translation of
      this knowledge into regenerative strategies in human spinal and brain injury, as
      well as stroke. 

PMID- 23881456
TI  - Growth inhibition and apoptosis-inducing effects of cudraflavone B in human oral
      cancer cells via MAPK, NF-kappaB, and SIRT1 signaling pathway.
AB  - The goal of this study was to investigate the effect and molecular mechanism of
      cudraflavone B, a prenylated flavonoid isolated from the root bark of Cudrania
      tricuspidata, against oral squamous cell carcinoma cells. We observed that
      cudraflavone B inhibited proliferation of these cells in a time- and dose
      dependent manner. At 15 uM, cudraflavone B induced cell death via apoptosis
      (characterized by the appearance of nuclear morphology) and increased the
      accumulation of the sub-G1 peak (portion of apoptotic annexin V positive cells).
      Treatment with cudraflavone B triggered the mitochondrial apoptotic pathway
      (indicated by induction of the proapoptotic protein p53 and the p21 and p27
      effector proteins), downregulation of cell cycle regulatory proteins (e.g., p-Rb,
      changing Bax/Bcl-2 ratios, cytochrome-c release), and caspase-3 activation.
      Cudraflavone B time-dependently activated NF-kappaB, the MAP kinases p38, and
      ERK, and induced the expression of SIRT1. SIRT1 activator, resveratrol, dose
      dependently attenuated the growth-inhibitory and apoptosis-inducing effect of
      cudraflavone B and blocked cudraflavone B-induced regulatory protein expressions
      in the mitochondrial pathway such as p53, p21, p27, Bax, caspase-3, and
      cytochrome-c. Conversely, treatment with SIRT1 inhibitor sirtinol caused opposite
      effects. These results demonstrate for the first time that the molecular
      mechanism underlying the antitumor effect in oral squamous cell carcinoma cells
      is related to the activation of MAPK/and NF-kappaB as well as of the SIRT1
      pathway. Therefore, cudraflavone B may be a lead for the development of a
      potential candidate for human oral squamous cell carcinoma cells. 

PMID- 23881457
TI  - Triterpenoids and steroids with cytotoxic activity from Emmenopterys henryi.
AB  - Two new ursane-type triterpenoids, 3beta,19alpha,23-trihydroxyurs-12-en-24-al-28
      oic acid (1) and 3beta,19alpha,24-trihydroxy-23-norurs-12-en-28-oic acid (2), two
      new pregnane derivatives, 3beta,12beta-dihydroxy-5alpha-pregnane-14,16-dien-20
      one (9) and 12beta-hydroxy-5alpha-pregnane-14,16-dien-3,20-dione (10), and eight
      known compounds were isolated from the twigs and leaves of Emmenopterys henryi.
      The structures of the new compounds were elucidated on the basis of extensive
      spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 4, 11, and
      12 showed cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell
      lines with IC50 values in the range of 3.11-20.12 uM. 

PMID- 23881458
TI  - Unveiling ontogenesis of herbal medicine in plant chemical profiles by infrared
      macro-fingerprinting.
AB  - Given that harvesting time has a great impact on the quality of herbal medicine,
      knowing the ontogenesis in the chemical profile aspect is essential to determine
      the optimal harvesting season. A high-throughput and versatile approach (herbal
      infrared macro-fingerprinting) harmonizing with the character of herbal medicine
      and providing the whole chemical profile (entirety), group analogues (part), and
      single compounds (major components) is developed to rapidly disclose the
      variation rule of the full chemical profile of herbal medicine over a growing
      season without extraction pretreatments, and thus to determine the optimal
      harvesting period in respect to groups of chemical compounds using Scutellaria
      baicalensis as a demonstration. IR macro-fingerprints of Scutellaria baicalensis
      harvested in the same period have a high similarity (> 0.91) despite small
      variations, suggesting that IR macro-fingerprinting can faithfully reflect the
      spectacle of "disordered order" in nature. From Year-1 spring to Year-3 autumn,
      general contents (%, w/w) of total flavonoids fluctuate up and down with a
      maximum value in Year-2 spring, and that of saccharides is relatively stable
      except for the attenuation from Year-2 autumn to Year-3 spring. From Year-1
      autumn to Year-2 spring, flavonoid aglycones initially produced in Scutellaria
      baicalensis are extensively transformed to responding flavonoid glycosides. From
      Year-2 spring to Year-3 autumn, flavonoid glycosides are converted back to their
      corresponding aglycones. The best seasons for collecting Scutellaria baicalensis
      with a high content of flavonoid glycosides and aglycones would be Year-2 spring
      and Year-3 spring, respectively. 

PMID- 23881463
TI  - Identification of microRNAs associated with lymphangiogenesis in human gastric
      cancer.
AB  - PURPOSE: Lymphatic metastasis is a primary cause of gastric cancer-related death,
      yet factors governing tumor cell lymphatic metastasis have not been fully
      elucidated. MicroRNAs (miRNAs) are a recently discovered class of regulatory, non
      coding RNAs, some of which are involved in gastric cancer progression. However,
      little is known about which miRNA contributes to the lymphatic metastasis in
      human gastric cancer. This prompted us to find the significant miRNAs associated
      with lymphangiogenesis in human gastric cancer. METHODS: We screened vascular
      endothelial growth factor C (VEGF-C) expression in several gastric cancer cell
      lines as well as in the immortalized human gastric mucosal cell line GES-1, by
      real-time reverse transcriptase PCR (qRT-PCR). The gastric cancer cell lines MKN
      45 and SGC-7901, which have commonly been cultured with human lymphatic
      endothelial cells (HLECs) in vitro, promoted tube formation of HLECs following
      transformation with a VEGF-C expression vector. Using microarrays, we identified
      a panel of differentially expressed miRNAs in HLECs that had been co-cultured
      with VEGF-C-transformed gastric cancer cells compared with non-transformed
      gastric cancer cells. A subset of miRNAs was further validated using qRT-PCR.
      RESULTS: We found altered expression of miRNAs in HLECs co-cultured with
      lymphangiogenesis-inducing VEGF-C-transformed gastric cancer cells, with 47 up
      regulated and 42 down-regulated miRNAs. These findings were confirmed by qRT-PCR
      of selected miRNAs. Furthermore, several miRNAs were differentially expressed in
      patients with positive lymphatic metastasis of the primary gastric tumor. Up
      regulated miRNAs included miR-648, miR-5002-3p, miR-4754, miR-4760-5p, miR-4491,
      miR-4252, miR-5007-3p, and miR-647; and down-regulated miRNAs included miR-3178,
      miR-593-5p, miR-4485, miR-135a-3p, miR-17, miR-1469, and miR-124-5p. CONCLUSIONS:
      Several lymphangiogenesis-related miRNAs are significantly altered during
      lymphatic metastasis of gastric cancer.

PMID- 23881464
TI  - Minimally invasive osteosynthesis of adult tibia fractures by means of rigid
      fixation with anatomic locked plates.
AB  - Main principle of biological fixation by minimally invasive locked plate
      osteosynthesis (MILPO) in lower extremity long bone fractures is relative
      stability which is provided by using long plate with limited number of screws.
      Some biomechanical studies have been reported about this issue. However, clinical
      studies are still missing. The aims of this retrospective extended case series
      were to evaluate the clinical and radiological results of adult tibia fractures
      treated by MILPO and the effect of plate length and screw density on complication
      rates. Twenty tibia fractures in 19 patients (mean age 42.3 years) operated by
      MILPO were reviewed. According to the AO classification, diaphyseal and
      metaphyseal fractures without intraarticular extensions were simple and wedge
      type fractures, whereas all intraarticular fractures were comminuted. Number of
      screws, cortices and empty screw holes proximal and distal to the fracture, plate
      span ratio (plate length divided by overall fracture length), plate-screw density
      (number of inserted screws divided by number of plate holes), fixation failures,
      delayed or nonunion, malalignment and leg length discrepancy were documented.
      Mean follow-up was 16 (range 12-26) months. On average, 4 screws with 6 cortices
      were used both proximally and distally in all fractures. Only in diaphyseal
      fractures, one screw hole close to the fracture was omitted. Average plate-screw
      density and plate-span ratio were 0.68 and 4, respectively. Mean union time was 3
      months. There were no cases of delayed or nonunion on the final follow-up. Plate
      bending was observed in one patient who had fair result. The remaining 18 (94.8
      %) patients showed good and excellent results. Satisfactory results can be
      achieved despite low plate-span ratio and high plate-screw density in simple and
      wedge-type diaphyseal fractures of the tibia. Additionally, plate-screw density
      can be higher at metaphysis in intraarticular fractures, in which essential point
      is a perfectly stable fixation that provides early motion. 

PMID- 23881465
TI  - Dietary antioxidants, cognitive function and dementia--a systematic review.
AB  - Antioxidant compounds, contained in fruit, vegetables and tea, have been
      postulated to have a protective effect against age-related cognitive decline by
      combating oxidative stress. However, recent research on this subject has been
      conflicting. The aim of this systematic review was to consider current
      epidemiological and longitudinal evidence for an association between habitual
      dietary intake of antioxidants and cognition, with consideration given to both
      cognitive functioning and risk for dementia and its subtypes, including
      Alzheimer's disease and vascular dementia. Searches of electronic databases were
      undertaken to identify peer-reviewed journal articles that reported on
      associations between antioxidant intakes (vitamins C, E, flavonoids, carotenoids)
      and cognitive function or risk for dementia. Eight cross-sectional and 13
      longitudinal studies were identified and included in the review. There were mixed
      findings for the association between antioxidant intake, cognition and risk of
      dementia and Alzheimer's disease. Large heterogeneity in study design,
      differential control of confounders, insufficient measures of cognitive
      performance, and difficulties associated with dietary assessment may contribute
      to the inconsistent findings. Overall, findings do not consistently show habitual
      intakes of dietary antioxidants are associated with better cognitive performance
      or a reduced risk for dementia. Future intervention trials are warranted to
      elucidate the effects of a high intake of dietary antioxidants on cognitive
      functioning, and to explore effects within a whole dietary pattern. 

PMID- 23881466
TI  - Laparoscopic direct suture of perforation after diagnostic colonoscopy.
AB  - BACKGROUND: Increasing colonoscopy use increases the incidence of iatrogenic
      colon perforation. Operative management of iatrogenic colonoscopic perforation is
      diverse. This study retrospectively reviewed our experiences in treating
      diagnostic colonoscopy-associated bowel perforation by laparoscopic direct
      suturing. METHODS: A total of 89,014 patients underwent diagnostic colonoscopy at
      our institution during the past 6 years. We identified 17 iatrogenic perforations
      (0.019 %) that were all managed by laparoscopic direct suturing. RESULTS:
      Perforation patients included 11 men and 6 women (mean age 60 +/- 18 years).
      Sixteen patients (94 %) had severe comorbidities or previous abdominal surgery.
      Perforations were noticed by the endoscopist during the procedure in 13 cases (76
      %) while the remaining 4 cases (24 %) were diagnosed within 24 h after
      colonoscopy. The estimated mean longitudinal perforation length was 4.4 +/- 2.1
      cm. Mean operation time was 2.3 +/- 0.6 h, without significant blood loss or
      other severe complication. The mean time to bowel function return was 3.4 +/- 1.2
      days, the mean time to initial oral intake was 3.9 +/- 2.0 days and the mean
      hospitalization duration was 6.8 +/- 4.2 days. CONCLUSIONS: Diagnostic
      colonoscopic perforation occurred in less than 2/10,000 patients when colonoscopy
      was performed by experienced operators in our endoscopy center. Most of the
      perforation patients had severe comorbidities, to which the surgeon should pay
      close attention during colonoscopy. Laparoscopic primary suture of colon
      perforations caused by diagnostic colonoscopy is a safe and feasible repair
      method. Further efforts will definitively assess the feasibility of routinely
      using laparoscopic direct suture to repair colon perforations.

PMID- 23881467
TI  - Application of photo-selective films to manipulate wavelength of transmitted
      radiation and photosynthate composition in red beet (Beta vulgaris var. conditiva
      Alef.).
AB  - BACKGROUND: Interest is increasing around both the use of plants as functional
      foods and the agronomic techniques which can increase nutrients and
      phytochemicals. Nevertheless, little research has focused on the effects of light
      on accumulation of active compounds in root storage organs. Red beet was treated
      with RED (red/far red ratio: 1.29; transmitted photosynthetically active
      radiation: 66.9%) and GREEN (red/far red ratio: 0.43; transmitted
      photosynthetically active radiation: 25.8%) photo-selective films and changes in
      nutrients and biomass accumulation were measured. RESULTS: Plants subjected to
      GREEN treatment had less dry weight accumulation both in storage roots (68%) and
      leaves (42%); moreover, soluble and structural carbohydrate concentration in
      roots was increased, as were the K, Mg and Zn concentrations (40.08, 2.95 and
      0.023 mg g-1 fresh weight, respectively). Conversely, GREEN lowered total
      phenolic concentration (0.33 vs. 0.47 mg g-1 fresh weight) and antioxidant
      activity (0.65 vs. 0.94 um Trolox equivalents g-1 fresh weight) compared to
      CONTROL. Total pigment concentration was reduced by 20% and 48% with RED and
      GREEN treatments, respectively. CONCLUSION: Red beet showed a strong plasticity
      in its adaptation to light availability. Some macronutrients (fiber, sugars,
      minerals) can be concentrated in roots by modifying the amount and quality of the
      light, principally with GREEN photo-selective films.

PMID- 23881469
TI  - Abstracts of the 9th International Conference On Homocysteine and One-Carbon
      Metabolism - HCY2013. Dublin, Ireland. September 8-12, 2013.

PMID- 23881468
TI  - The complement and immunoglobulin levels in NMO patients.
AB  - Since the discovery of aquaporin-4 (AQP4) antibody a decade ago, neuromyelitis
      optica (NMO) has been distinguished from multiple sclerosis (MS). MS mainly
      features T lymphocyte-oriented autoimmune responses while NMO is more precisely
      influenced by humoral immunity, among which the complement activation has always
      been reckoned as an important mechanism. The AQP4 antibody, namely NMO-IgG, adds
      to new evidence of how complement affects the severity of NMO. We compared the
      levels of complement (C3, C4, CH50) and immunoglobulins (IgG, IgM, IgA) between
      NMO patients and controls. Groups with AQP4 antibody positive and negative NMO
      patients were also compared with controls, respectively, aiming to elaborate on
      the relationship between complement activation and immunoglobulins. We also
      compared these indexes together with expanded disability status scale (EDSS)
      between two different groups in NMO patients and endeavored to figure out their
      correlations with each other. Complement and immunoglobulins were compared
      between NMO patients in acute phase and non-acute phase of the disease to find
      out the level fluctuation of CH50 and other indexes during different stages of
      NMO. We analyzed NMO patients (n = 88) and controls (n = 44) for IgG, IgM, IgA,
      other indexes like CH50, C3, C4 have also been explored between the two groups.
      Furthermore, we investigated whether these antibodies could mediate complement
      dependent cytotoxicity. Thus, the NMO patients were split into two groups with or
      without AQP4 antibody to find out the status of NMO-IgG in the development and
      severity of the disease. EDSS was used as criteria for the evaluating the
      seriousness of NMO. Comparison between NMO patients in acute stage and non-acute
      stage of the disease was also made for a better understanding of the disease.
      Compared with controls, NMO patients had much higher IgG (13.984 +/- 5.981 mg/ml,
      11.430 +/- 3.254 mg/ml, P < 0.01) but lower CH50 (respectively, 43.55 +/- 12.172
      U/L, 50.66 +/- 12.523 U/L, P < 0.01). While IgG increased in Anti-AQP4 antibody
      positive NMO patients, CH50 dropped in this group when compared with AQP4
      negative patients. When compared with controls, both of the NMO groups had
      enhanced IgG and decreased CH50 though only AQP4-positive NMO patients showed
      significance (IgG 15.004 +/- 6.613 mg/ml, 11.430 +/- 3.254 mg/ml, P < 0.01)
      (CH50, respectively, 41.12 +/- 12.581U/L, 50.66 +/- 12.523 U/L, P < 0.01). C4 was
      also decreased though without evident significance (0.215 +/- 0.118 mg/ml, 0.260
      +/- 0.133 mg/ml, P = 0.069). Those NMO patients in acute phase (with the course
      of newly attack of less than 1 month) had increased immunoglobulin (IgG 14.991 +/
      6.639 mg/ml, 12.460 +/- 4.490 mg/ml) but decreased complement (CH50 42.755 +/-
      12.403 U/L, 44.743 +/- 11.890 U/L) than those who passed the acute phase. There
      was correlation between IgG and CH50 (R = -0.402, P < 0.01) in NMO patients.
      Relationship was also found between IgG and EDSS (R = 0.609, P < 0.001), CH50 and
      EDSS (R = -0.333, P < 0.01). These results indicate that NMO patients had
      enhanced immunoglobulin in acute phase but decreased complement. The complement
      was correlated with immunoglobulin. Among the two NMO groups, the complement
      system was only activated in NMO-IgG positive patients, which might indicate a
      potential different pathogenetic mechanism in NMO-IgG negative patients. Also,
      patients' disability of the former group was more serious than their
      counterparts. Those patients in acute phase obviously had increased
      immunoglobulin but decreased complement. Thus, we have come to the conclusion
      that in AQP4-positive NMO patients, immunoglobulin activates complement system,
      which influences the functions of NMO patients.

PMID- 23881471
TI  - Aspirin use is associated with lower prostate cancer risk in male carriers of
      BRCA mutations.
AB  - Previous studies have shown that male BRCA mutation carriers stand at increased
      risk of developing prostate cancer and have concerns about developing cancer.
      Genetic counseling practitioners often discuss strategies for reducing the risk
      of cancer for patients at high risk due to their genetic background. Addressing
      modifiable health habits is one such strategy. Unfortunately, modifiable risk
      factors for prostate cancer have only been documented in the general population
      and have not yet been studied in the BRCA carrier subpopulation. Therefore, this
      study aimed to identify modifiable risk factors for prostate cancer in BRCA
      carriers. We examined prostate cancer risk factors in 74 men who were part of
      families with a BRCA mutation. This study examined nine dichotomous variables
      including: exercise, history of vasectomy, smoking history, alcohol use,
      finasteride use, statin use, aspirin use, coffee use, and vitamin use. The survey
      was sent to all cases of prostate cancer in the Hereditary Cancer Center Database
      at Creighton University with a known BRCA status. This study confirmed the
      protective benefits of daily aspirin use, which have been observed in previous
      studies of the general population, and suggests its benefit in BRCA carriers.
      Protective benefits from regular vigorous exercise and daily coffee use trended
      towards significance, but neither factor withstood the Bonferroni Correction for
      multiple comparisons. 

PMID- 23881472
TI  - Psychosocial burden of sickle cell disease on parents with an affected child in
      Cameroon.
AB  - The chronicity of Sickle Cell Disease (SCD) could impair the quality of life of
      caregivers. We performed a quantitative study to assess various indices of
      psychosocial burden on Cameroonian parents (N = 130) with at least one living SCD
      affected child. Demographic and medical information were obtained from the
      participants and the review of the patients' medical records. The survey
      instrument included a 38-item stress factors scale using Likert-type statements,
      evaluating general perceptions of stress and five main specific stressors:
      disease factors (clinical severity), hospital factors, financial factors, family
      factors (life/dynamic) and SCD-child factors (perceived quality of life). The
      items pertaining to burden involved four response options with increasing
      severity: 0, 1, 2 or 3. Descriptive statistics and non-parametric tests were used
      for analysis. Participants were typically aged 38 years, urban dwellers (89%),
      female (80%), married (60.2%), employed (61.7%) and had secondary/tertiary
      education (82%). Median age of SCD-affected children was 9 years. The median age
      at diagnosis of SCD was 6 months; 47.8% had more than 3 painful crises per year.
      The majority of participants (88.3%) experienced moderate to severe difficulty
      coping with SCD. On a 0-3 scale, median score of SCD clinical severity was the
      major factor to undermine the coping ability of parents (2.2); vaso-occlusive
      painful events (>3 per year) was the disease-related stressor that most impacted
      their coping ability. The family life dynamic was the least stressful (0.7).
      Unemployment affected all the stressors' categories. Stressors scores also
      increased with female, single, low education level, age of SCD-affected children
      or more than 3 children in the family. In Cameroon, there is an urgent need to
      implement practices that ensure affordable access to health-care and activities
      that would reduce SCD morbidity.

PMID- 23881474
TI  - A direct thin-film path towards low-cost large-area III-V photovoltaics.
AB  - III-V photovoltaics (PVs) have demonstrated the highest power conversion
      efficiencies for both single- and multi-junction cells. However, expensive
      epitaxial growth substrates, low precursor utilization rates, long growth times,
      and large equipment investments restrict applications to concentrated and space
      photovoltaics (PVs). Here, we demonstrate the first vapor-liquid-solid (VLS)
      growth of high-quality III-V thin-films on metal foils as a promising platform
      for large-area terrestrial PVs overcoming the above obstacles. We demonstrate 1-3
      MUm thick InP thin-films on Mo foils with ultra-large grain size up to 100 MUm,
      which is ~100 times larger than those obtained by conventional growth processes.
      The films exhibit electron mobilities as high as 500 cm2/V-s and minority carrier
      lifetimes as long as 2.5 ns. Furthermore, under 1-sun equivalent illumination,
      photoluminescence efficiency measurements indicate that an open circuit voltage
      of up to 930 mV can be achieved, only 40 mV lower than measured on a single
      crystal reference wafer.

PMID- 23881473
TI  - Newborn screening: education, consent, and the residual blood spot. The position
      of the national society of genetic counselors.
AB  - Newborn screening (NBS) is a minimally invasive lifesaving test. There is
      currently no federal mandate for NBS, thus states determine their own screening
      panel based on the recommendations of the Secretary's Advisory Committee on
      Heritable Disorders in Newborn and Children (SACHDNC), which was recently re
      chartered as the Discretionary Advisory Committee on Heritable Disorders in
      Newborns and Children (DACHDNC). After NBS is completed, a couple of residual
      blood spots remain. While some states allow these spots to be used for public
      health and scientific research purposes, parents are not always informed about
      these additional uses. This paper addresses the National Society of Genetic
      Counselors' (NSGC's) position about NBS and blood spot storage/use and the
      rationale for these positions. The National Society of Genetic Counselors
      strongly supports newborn screening for the uniform screening panel of conditions
      recommended by the Secretary's Advisory Committee on Heritable Disorders in
      Newborns and Children. NSGC also supports storage and use of blood spot samples
      by newborn screening laboratories and transparent policies that govern these
      activities. 

PMID- 23881475
TI  - Trivalent scandium, yttrium and lanthanide complexes with thia-oxa and selena-oxa
      macrocycles and crown ether coordination.
AB  - Complexes of the oxa-thia macrocycles [18]aneO4S2, [15]aneO3S2 and the oxa-selena
      macrocycle [18]aneO4Se2 (L) of types [MCl2(L)]FeCl4 (M = Sc or Y) were prepared
      from [ScCl3(thf)3] or [YCl2(THF)5][YCl4(THF)2] and the ligand in anhydrous MeCN,
      using FeCl3 as a chloride abstractor. The [MI2(L)]I, [LaI3(L)] and [LuI2(L)]I
      have been prepared from the ligands and the appropriate anhydrous metal triiodide
      in MeCN. Complexes of type [LaI3(crown)] and [LuI2(crown)]I (crown = 18-crown-6,
      15-crown-5) were made for comparison. Use of the metal iodide results in
      complexes with high solubility compared to the corresponding chlorides, although
      also with increased sensitivity to moisture. All complexes were characterised by
      microanalysis, IR, (1)H, (45)Sc and (77)Se NMR spectroscopy as appropriate. X-ray
      crystal structures are reported for [ScCl2([18]aneO4S2)][FeCl4],
      [ScI2([18]aneO4S2)]I, [YCl2(18-crown-6)]3[Y2Cl9], [YCl2([18]aneO4S2)][FeCl4],
      [LaI3(15-crown-5)], [LaI2(18-crown-6)(MeCN)]I, [LuI(18-crown-6)(MeCN)2]I2, [Lu(15
      crown-5)(MeCN)2(OH2)]I3, [LaI3([18]aneO4S2)], [LaI([18]aneO4S2)(OH2)]I2,
      [LaI3([18]aneO4Se2)] and [LuI2([18]aneO4Se2)]I. In each complex all the neutral
      donor atoms of the macrocycles are coordinated to the metal centre, showing very
      rare examples of these oxophilic metal centres coordinated to thioether groups,
      and the first examples of coordinated selenoether donors. In some cases MeCN or
      adventitious water displaces halide ligands, but not the S/Se donors from La or
      Lu complexes. A complex of the oxa-tellura macrocycle [18]aneO4Te2,
      [ScCl2([18]aneO4Te2)][FeCl4] was isolated, but is unstable in MeCN solution,
      depositing elemental Te. YCl3 and 18-crown-6 produced [YCl2(18-crown-6)]3[Y2Cl9],
      the asymmetric unit of which contains two cations with a trans-YCl2 arrangement
      and a third with a cis-YCl2 group. 

PMID- 23881476
TI  - Newer innovations in treatment of retracted nipple: correspondence.

PMID- 23881477
TI  - Newer innovations in treatment of retracted nipple: authors' reply.

PMID- 23881478
TI  - Urinary infections in children.
AB  - Urinary tract infection (UTI) is a common infection in infants and children.
      During infancy, boys are more commonly affected than girls and thereafter, female
      preponderance is found. Presentation varies among different age groups. Clinical
      features in neonates and young infants are non-specific, manifest as septicemia
      where a high index of suspicion is needed. Older children typically present as
      simple or complicated UTI. Rapid diagnosis, institution of early treatment and
      further evaluation by imaging modalities are of utmost importance. The prevention
      of recurrent UTI and detection of congenital anomalies of kidney and urinary
      tract are major objectives in the management. Use of ultrasound is required to
      detect underlying congenital abnormalities, whereas voiding cystourethrogram and
      dimercaptosuccinic acid (DMSA) scan are useful in the diagnosis of obstructive
      uropathy and vesicoureteric reflux and renal scar, respectively. The children
      requiring surgical interventions are to be recognised early to prevent recurrent
      UTI. The treatment of vesicoureteric reflux by chemoprophylaxis in lower grades
      and surgical treatment in higher grades are important consideration in prevention
      of recurrent UTI. This is required to prevent renal parenchymal damage and
      scarring that can cause hypertension and progressive renal insufficiency in later
      life. 

PMID- 23881479
TI  - Pyomyositis in unusual site (subscapularis and infraspinatus muscles).

PMID- 23881480
TI  - Group B streptococcal meningitis in infants beyond the neonatal period.
AB  - OBJECTIVES: To describe the clinico-bacteriological profile, and early outcomes
      of infants diagnosed with Group B streptococcus (GBS) meningitis. METHODS: This
      was a retrospective review of infants (aged 1 mo to 2 y) diagnosed with GBS
      meningitis in a tertiary care hospital in New Delhi from October 2010 through
      January 2012. The clinico-bacteriological data and early outcomes of infants with
      suspected bacterial meningitis and a positive CSF latex agglutination test for
      GBS were studied. The CSF samples were subjected to PCR for broad spectrum 16s
      ribosomal DNA and the GBS species specific gene, the scpB. RESULTS: Twenty seven
      patients (13 boys, and 14 girls) were diagnosed with GBS meningitis during the
      study period. Broad spectrum 16s ribosomal DNA PCR was performed on 18 of the 27
      CSF samples. Sixteen were positive. All these 16 were also positive for the
      species specific scpB gene. The median duration of hospital stay was 7 d (range 1
      72 d). Nine patients died. One patient each developed ventriculitis, optic
      atrophy and hydrocephalus. Overall, 12 patients had a complete recovery at
      discharge. CONCLUSIONS: GBS must be considered in the etiology of bacterial
      meningitis in Indian infants.

PMID- 23881481
TI  - HIV with juvenile dermatomyositis.
AB  - Dermatomyositis with HIV infection has been very rarely reported. The authors
      report an 8-y-old boy who presented with skin rashes and edema, muscle weakness
      and polymicrobial infection along with mild immunosupression. Diagnosis of
      dermatomyositis was established by raised enzymes, suggestive MRI and muscle
      biopsy findings. Child responded to systemic steroids and low dose weekly
      methotrexate. 

PMID- 23881482
TI  - Factor v deficiency: a subtle presentation.
AB  - Congenital factor V deficiency (also known as labile factor or proaccelerin) is a
      rather uncommon [1:1000,000] inherited coagulopathy (autosomal recessive
      inheritance). Affected patients become symptomatic in early childhood with
      spontaneous or post-traumatic bleeding complications. The authors report an
      infant who presented with a much feared complication of the same probably as a
      neonatal presentation. 

PMID- 23881483
TI  - Sunlight and free radicals.

PMID- 23881489
TI  - Antibiotics: blocking bacterial defences.

PMID- 23881490
TI  - Computational chemistry: a multitude of spins.

PMID- 23881491
TI  - Heparin sensing: blue-chip binding.

PMID- 23881492
TI  - Macrocyclic chemistry: a star is born.

PMID- 23881493
TI  - Inorganic materials: intuition weaved into computation.

PMID- 23881494
TI  - Metallacycles: breaking the rules.

PMID- 23881495
TI  - Single-molecule interrogation of a bacterial sugar transporter allows the
      discovery of an extracellular inhibitor.
AB  - Capsular polysaccharides form the outermost protective layer around many Gram
      negative bacteria. Antibiotics aimed directly at weakening this layer are not yet
      available. In pathogenic Escherichia coli E69, a protein, Wza, forms a pore in
      the outer membrane that transports K30 capsular polysaccharide from its site of
      synthesis to the outside of the cell. This therefore represents a prospective
      antibiotic target. Here we test a variety of grommet-like mimics of K30 capsular
      polysaccharide on wild-type Wza and on mutant open forms of the pore by
      electrical recording in planar lipid bilayers. The most effective glycomimetic
      was the unnatural cyclic octasaccharide octakis(6-deoxy-6-amino)cyclomaltooctaose
      (am8gammaCD), which blocks the alpha-helix barrel of Wza, a site that is directly
      accessible from the external medium. This glycomimetic inhibited K30
      polysaccharide transport in live E. coli E69. With the protective outer membrane
      disrupted, the bacteria can be recognized and killed by the human immune system.

PMID- 23881496
TI  - Entangled quantum electronic wavefunctions of the Mn4CaO5 cluster in photosystem
      II.
AB  - It is a long-standing goal to understand the reaction mechanisms of catalytic
      metalloenzymes at an entangled many-electron level, but this is hampered by the
      exponential complexity of quantum mechanics. Here, by exploiting the special
      structure of physical quantum states and using the density matrix renormalization
      group, we compute near-exact many-electron wavefunctions of the Mn4CaO5 cluster
      of photosystem II, with more than 1 * 10(18) quantum degrees of freedom. This is
      the first treatment of photosystem II beyond the single-electron picture of
      density functional theory. Our calculations support recent modifications to the
      structure determined by X-ray crystallography. We further identify multiple low
      lying energy surfaces associated with the structural distortion seen using X-ray
      crystallography, highlighting multistate reactivity in the chemistry of the
      cluster. Direct determination of Mn spin-projections from our wavefunctions
      suggests that current candidates that have been recently distinguished using
      parameterized spin models should be reassessed. Through entanglement maps, we
      reveal rich information contained in the wavefunctions on bonding changes in the
      cycle. 

PMID- 23881497
TI  - Direct catalytic cross-coupling of organolithium compounds.
AB  - Catalytic carbon-carbon bond formation based on cross-coupling reactions plays a
      central role in the production of natural products, pharmaceuticals,
      agrochemicals and organic materials. Coupling reactions of a variety of
      organometallic reagents and organic halides have changed the face of modern
      synthetic chemistry. However, the high reactivity and poor selectivity of common
      organolithium reagents have largely prohibited their use as a viable partner in
      direct catalytic cross-coupling. Here we report that in the presence of a Pd
      phosphine catalyst, a wide range of alkyl-, aryl- and heteroaryl-lithium reagents
      undergo selective cross-coupling with aryl- and alkenyl-bromides. The process
      proceeds quickly under mild conditions (room temperature) and avoids the
      notorious lithium halogen exchange and homocoupling. The preparation of key alkyl
      , aryl- and heterobiaryl intermediates reported here highlights the potential of
      these cross-coupling reactions for medicinal chemistry and material science. 

PMID- 23881498
TI  - Magnetic relaxation pathways in lanthanide single-molecule magnets.
AB  - Single-molecule magnets are compounds that exhibit magnetic bistability caused by
      an energy barrier for the reversal of magnetization (relaxation). Lanthanide
      compounds are proving promising as single-molecule magnets: recent studies show
      that terbium phthalocyanine complexes possess large energy barriers, and
      dysprosium and terbium complexes bridged by an N2(3-) radical ligand exhibit
      magnetic hysteresis up to 13 K. Magnetic relaxation is typically controlled by
      single-ion factors rather than magnetic exchange (whether one or more 4f ions are
      present) and proceeds through thermal relaxation of the lowest excited states.
      Here we report polylanthanide alkoxide cage complexes, and their doped
      diamagnetic yttrium analogues, in which competing relaxation pathways are
      observed and relaxation through the first excited state can be quenched. This
      leads to energy barriers for relaxation of magnetization that exceed 800 K. We
      investigated the factors at the lanthanide sites that govern this behaviour.

PMID- 23881499
TI  - Total synthesis of the Daphniphyllum alkaloid daphenylline.
AB  - The Daphniphyllum alkaloids are a large class of natural products isolated from a
      genus of evergreen plants widely used in Chinese herbal medicine. They display a
      remarkable range of biological activities, including anticancer, antioxidant, and
      vasorelaxation properties as well as elevation of nerve growth factor.
      Daphenylline is a structurally unique member among the predominately aliphatic
      Daphniphyllum alkaloids, and contains a tetrasubstituted arene moiety mounted on
      a sterically compact hexacyclic scaffold. Herein, we describe the first total
      synthesis of daphenylline. A gold-catalysed 6-exo-dig cyclization reaction and a
      subsequent intramolecular Michael addition reaction, inspired by Dixon's seminal
      work, were exploited to construct the bridged 6,6,5-tricyclic motif of the
      natural product at an early stage, and the aromatic moiety was forged through a
      photoinduced olefin isomerization/6pi-electrocyclization cascade followed by an
      oxidative aromatization process. 

PMID- 23881500
TI  - The Janus-faced role of external forces in mechanochemical disulfide bond
      cleavage.
AB  - Recent force microscopy measurements on the mechanically activated cleavage of a
      protein disulfide bond through reaction with hydroxide ions revealed that for
      forces greater than 0.5 nN, the acceleration of the reaction rate is
      substantially reduced. Here, using ab initio simulations, we trace this
      'reactivity switch' back to a dual role played by the mechanical force, which
      leads to antagonistic effects. On the one hand, the force performs work on the
      system, and thereby accelerates the reaction. On the other hand, the force also
      induces a conformational distortion that involves the S-S-C-C dihedral angle,
      which drives the disulfide into a conformation that is shielded against
      nucleophilic attack because of steric hindrance. The discovery of force-induced
      conformational changes that steer chemical reactivity provides a new key concept
      that is expected to be relevant beyond this specific case, for example in
      understanding how 'disulfide switches' regulate protein function and for the
      rational design of mechanoresponsive materials.

PMID- 23881501
TI  - A dendritic single-molecule fluorescent probe that is monovalent, photostable and
      minimally blinking.
AB  - Single-molecule fluorescence techniques have emerged as a powerful approach to
      understanding complex biological systems. However, a challenge researchers still
      face is the limited photostability of nearly all organic fluorophores, including
      the cyanine and Alexa dyes. We report a new, monovalent probe that emits in the
      far-red region of the visible spectrum with properties desirable for single
      molecule optical imaging. This probe is based on a ring-fused boron
      dipyrromethene (BODIPY) core that is conjugated to a polyglycerol dendrimer
      (PGD). The dendrimer makes the hydrophobic fluorophore water-soluble. This probe
      exhibits excellent brightness, with an emission maximum of 705 nm. We have
      observed strikingly long and stable emission from individual PGD-BODIPY probes,
      even in the absence of anti-fading agents such as Trolox, a combined oxidizing
      reducing agent often used in single-molecule studies for improving the
      photostability of common imaging probes. These interesting properties greatly
      simplify use of the fluorophore.

PMID- 23881502
TI  - Stabilization of anti-aromatic and strained five-membered rings with a transition
      metal.
AB  - Anti-aromatic compounds, as well as small cyclic alkynes or carbynes, are
      particularly challenging synthetic goals. The combination of their destabilizing
      features hinders attempts to prepare molecules such as pentalyne, an 8pi-electron
      anti-aromatic bicycle with extremely high ring strain. Here we describe the
      facile synthesis of osmapentalyne derivatives that are thermally viable, despite
      containing the smallest angles observed so far at a carbyne carbon. The compounds
      are characterized using X-ray crystallography, and their computed energies and
      magnetic properties reveal aromatic character. Hence, the incorporation of the
      osmium centre not only reduces the ring strain of the parent pentalyne, but also
      converts its Huckel anti-aromaticity into Craig-type Mobius aromaticity in the
      metallapentalynes. The concept of aromaticity is thus extended to five-membered
      rings containing a metal-carbon triple bond. Moreover, these metal-aromatic
      compounds exhibit unusual optical effects such as near-infrared photoluminescence
      with particularly large Stokes shifts, long lifetimes and aggregation
      enhancement.

PMID- 23881503
TI  - A pentagonal cyanostar macrocycle with cyanostilbene CH donors binds anions and
      forms dialkylphosphate [3]rotaxanes.
AB  - Since the discovery of crown ethers, macrocycles have been recognized as powerful
      platforms for supramolecular chemistry. Although their numbers and variations are
      now legion, macrocycles that are simple to make using high-yielding reactions in
      one pot and on the multigram scale are rare. Here we present such a discovery
      obtained during the creation of a C5-symmetric cyanostilbene 'campestarene'
      macrocycle, cyanostar, that employs Knoevenagel condensations in the preparation
      of its cyanostilbene repeat unit. In the solid state, cyanostars form pi-stacked
      dimers constituted of chiral P and M enantiomers. The electropositive central
      cavity stabilizes anions with CH hydrogen-bonding units that are activated by
      electron-withdrawing cyano groups. In solution, the cyanostar shows high-affinity
      binding as 2:1 sandwich complexes, log beta2 ~ 12 and DeltaG ~ -70 kJ mol(-1), of
      large anions (BF4(-), ClO4(-) and PF6(-)) usually considered weakly coordinating.
      The cyanostar's size preference allowed formation of an unprecedented [3]rotaxane
      templated around a dialkylphosphate.

PMID- 23881504
TI  - Ultrafast above-threshold dynamics of the radical anion of a prototypical quinone
      electron-acceptor.
AB  - Quinones feature prominently as electron acceptors in nature. Their electron
      transfer reactions are often highly exergonic, for which Marcus theory predicts
      reduced electron-transfer rates because of a free-energy barrier that occurs in
      the inverted region. However, the electron-transfer kinetics that involve
      quinones can appear barrierless. Here, we consider the intrinsic properties of
      the para-benzoquinone radical anion, which serves as the prototypical electron
      transfer reaction product involving a quinone-based acceptor. Using time-resolved
      photoelectron spectroscopy and ab initio calculations, we show that excitation at
      400 and 480 nm yields excited states that are unbound with respect to electron
      loss. These excited states are shown to decay on a sub-40 fs timescale through a
      series of conical intersections with lower-lying excited states, ultimately to
      form the ground anionic state and avoid autodetachment. From an isolated electron
      acceptor perspective, this ultrafast stabilization mechanism accounts for the
      ability of para-benzoquinone to capture and retain electrons.

PMID- 23881505
TI  - A frustrated-Lewis-pair approach to catalytic reduction of alkynes to cis
      alkenes.
AB  - Frustrated Lewis pairs are compounds containing both Lewis acidic and Lewis basic
      moieties, where the formation of an adduct is prevented by steric hindrance. They
      are therefore highly reactive, and have been shown to be capable of heterolysis
      of molecular hydrogen, a property that has led to their use in hydrogenation
      reactions of polarized multiple bonds. Here, we describe a general approach to
      the hydrogenation of alkynes to cis-alkenes under mild conditions using the
      unique ansa-aminohydroborane as a catalyst. Our approach combines several
      reactions as the elementary steps of the catalytic cycle: hydroboration
      (substrate binding), heterolytic hydrogen splitting (typical frustrated-Lewis
      pair reactivity) and facile intramolecular protodeborylation (product release).
      The mechanism is verified by experimental and computational studies.

PMID- 23881506
TI  - Chlorine chronicles.

PMID- 23881507
TI  - Minimally invasive versus conventional extracorporeal circulation in minimally
      invasive cardiac valve surgery.
AB  - BACKGROUND: Minimally invasive extracorporeal circulation (MECC) technology was
      applied predominantly in coronary surgery. Data regarding the application of MECC
      in minimally invasive valve surgery are missing largely. PATIENTS AND METHODS:
      Patients undergoing isolated minimally invasive mitral or aortic valve procedures
      were allocated either to conventional extracorporeal circulation (CECC) group (n
      = 63) or MECC group (n = 105), and their prospectively generated data were
      analyzed. RESULTS: Demographic data were comparable between the groups regarding
      age (CECC vs. MECC: 71.0 +/- 7.5 vs. 66.2 +/- 10.1 years, p = 0.091) and logistic
      EuroSCORE I (6.2 +/- 2.5 vs. 5.4 +/- 3.0, p = 0.707). Hospital mortality was one
      patient in each group (1.6 vs. 1.0%, p = 0.688). The levels of leukocytes were
      lower in the MECC group (11.6 +/- 3.2 vs. 9.4 +/- 4.3 109/L, p = 0.040). Levels
      of platelets (137.2 +/- 45.5 vs. 152.4 +/- 50.3 109/L, p = 0.015) and hemoglobin
      (103.3 +/- 11.3 vs. 107.3 +/- 14.7 g/L, p = 0.017) were higher in the MECC group.
      Renal function was better preserved (creatinine: 1.1 +/- 0.4 vs. 0.9 +/- 0.2
      mg/dL, p = 0.019). We were able to validate shorter time of postoperative
      ventilation (9.5 +/- 15.1 vs. 6.3 +/- 3.4 h, p = 0.054) as well as significantly
      shorter intensive care unit (ICU) stay (1.8 +/- 1.3 vs. 1.2 +/- 1.0 d, p = 0.005)
      for MECC patients. The course of C-reactive protein did not differ between the
      groups. CONCLUSION: We were able to prove the feasibility of MECC even in
      minimally invasive performed mitral and aortic valve procedures. In addition, the
      use of MECC provides decreased platelet consumption and less hemodilution. The
      use of MECC in these selected patients lead to a shorter ventilation time and ICU
      stay.

PMID- 23881508
TI  - Cardiac liposarcoma-a review of outcome after surgical resection.
AB  - OBJECTIVE: This review was performed to pool the current surgical strategies for
      cardiac liposarcoma. METHODS: A literature search was performed and all studies
      published in full-text or abstract forms were eligible for inclusion without
      applying any language restrictions. Case reports without surgical intervention,
      reporting noncardiac liposarcoma, animal cases, or review articles were excluded
      after initial abstract review. Analyzed postoperative outcomes included
      intraoperative and in-hospital mortality, longest reported survival, and
      recrudescence. RESULTS: After a critical evaluation 53 unique surgically treated
      case reports published between the years 1966 and December 2012 were included in
      this review. Most of the reported cardiac liposarcoma are myxoid (49.1%),
      pleomorphic liposarcoma occur with a prevalence of 20.8%, and well-differentiated
      tumors are observed in 13.2%. One-year survival rate increases the more
      differentiated the tumor is categorized: 54.5% for pleomorphic, 65.4% for myxoid,
      and 100% for well-differentiated liposarcoma (p = 0.096). CONCLUSION: Total
      surgical resection of cardiac liposarcoma is the only curative option, as it
      tends to local and distant recurrence. Therefore, a frequent follow-up
      examination should be considered.

PMID- 23881509
TI  - Physical activity, age, and arthritis: exploring the relationships of major risk
      factors on biopsychosocial symptomology and disease status.
AB  - The prevalence of arthritis in aging populations continues to rapidly grow.
      Research has highlighted 2 principal risk factors for progression of arthritis
      related biopsychosocial symptoms: age and physical inactivity. This study
      examined the relationship between and within physical activity and age on
      biopsychosocial symptoms of arthritis in adults (age >= 30 yr). Hierarchical,
      multiple-regression analyses were conducted on the Canadian Community Health
      Survey (Cycle 4.2, 2009-2010, N = 19,103). Results revealed that more-active
      adults had significantly fewer symptoms (physical unstd. B = -.23, p <= .001;
      pyschosocial unstd. B = -.51, p <= .001). In addition, as age increased, physical
      symptoms intensified and psychosocial symptoms tapered (physical unstd. B = .24,
      p <= .001; psychosocial unstd. B = -.45, p <= .001). Inactive older adults had
      the highest level of physical symptoms, while inactive younger adults had the
      highest level of psychosocial symptoms (p <= .001). Findings highlight the need
      to target physical activity interventions to specific age cohorts and particular
      biopsychosocial symptomologies.

PMID- 23881510
TI  - Allergen immunotherapy extract treatment set preparation: making a safer and
      higher quality product for patients.
AB  - The best possible allergen immunotherapy clinical outcomes require the provision
      of high quality and safe allergen immunotherapy extract preparations. Evolving
      national guidelines and regulatory bodies have devoted special attention to the
      safe compounding of sterile products, including allergen extracts. It is
      incumbent upon allergists preparing extract treatment sets for patients to be
      familiar with and adopt training, procedures and safety measures that lead to
      standardized high quality products. Preparers and supervisors must maintain
      ongoing competency in aseptic technique and prescribing principles, such as
      probable effective dose ranges, allergen cross-reactivity, and separation of high
      protease-containing extracts from susceptible extracts. Accordingly, knowledge
      and application of vial labeling, diluent selection, standard operating
      procedures, mixing log documentation, and mixing condition principles are a
      necessity. Although there have been no instances of infectious complications from
      allergen immunotherapy in a century of clinical practice, continued vigilance in
      the use of measures that ensure extract sterility is paramount. A review of
      allergen immunotherapy preparation recommendations and best practices based on
      published national guidelines is presented. Further study of preparation measures
      and prescribing principles will continue to advance the practice of allergen
      immunotherapy and offer opportunities for refinement of current recommendations. 

PMID- 23881512
TI  - Density effect on great tit (Parus major) clutch size intensifies in a polluted
      environment.
AB  - Long-term data on a great tit (Parus major) population breeding in a metal
      polluted zone around a copper-nickel smelter indicate that, against expectations,
      the clutch size of this species is decreasing even though metal emissions in the
      area have decreased considerably over the past two decades. Here, we document
      long-term population-level changes in the clutch size of P. major and explore if
      changes in population density, population numbers of competing species, timing of
      breeding, breeding habitat, or female age distribution can explain decreasing
      clutch sizes. Clutch size of P. major decreased by one egg in the polluted zone
      during the past 21 years, while there was no significant change in clutch size in
      the unpolluted reference zone over this time period. Density of P. major nests
      was similar in both environments but increased threefold during the study period
      in both areas (from 0.8 to 2.4 nest/ha). In the polluted zone, clutch size has
      decreased as a response to a considerable increase in population density, while a
      corresponding density change in the unpolluted zone did not have such an effect.
      The other factors studied did not explain the clutch size trend. Fledgling
      numbers in the polluted environment have been relatively low since the beginning
      of the study period, and they do not show a corresponding decrease to that noted
      for the clutch size over the same time period. Our study shows that responses of
      commonly measured life-history parameters to anthropogenic pollution depend on
      the structure of the breeding population. Interactions between pollution and
      intrinsic population characters should therefore be taken into account in
      environmental studies.

PMID- 23881511
TI  - Non-pharmacologic therapies for atopic dermatitis.
AB  - Atopic dermatitis (AD) continues to present significant therapeutic challenges,
      especially in severe cases. Navigating the line between risk and benefit can be
      difficult for more powerful medications such as immunosuppressants, but non
      pharmacologic treatments are often overlooked and underutilized. Creative
      application of these more physical therapies can serve to minimize the
      pharmacologic treatments and their side effects, and possibly even create synergy
      between modalities, to maximize benefit to the patient. 

PMID- 23881513
TI  - Insect density-plant density relationships: a modified view of insect responses
      to resource concentrations.
AB  - Habitat area is an important predictor of spatial variation in animal densities.
      However, the area often correlates with the quantity of resources within
      habitats, complicating our understanding of the factors shaping animal
      distributions. We addressed this problem by investigating densities of insect
      herbivores in habitat patches with a constant area but varying numbers of plants.
      Using a mathematical model, predictions of scale-dependent immigration and
      emigration rates for insects into patches with different densities of host plants
      were derived. Moreover, a field experiment was conducted where the scaling
      properties of odour-mediated attraction in relation to the number of odour
      sources were estimated, in order to derive a prediction of immigration rates of
      olfactory searchers. The theoretical model predicted that we should expect
      immigration rates of contact and visual searchers to be determined by patch area,
      with a steep scaling coefficient, MU = -1. The field experiment suggested that
      olfactory searchers should show a less steep scaling coefficient, with MU ~ -0.5.
      A parameter estimation and analysis of published data revealed a correspondence
      between observations and predictions, and density-variation among groups could
      largely be explained by search behaviour. Aphids showed scaling coefficients
      corresponding to the prediction for contact/visual searchers, whereas moths,
      flies and beetles corresponded to the prediction for olfactory searchers. As
      density responses varied considerably among groups, and variation could be
      explained by a certain trait, we conclude that a general theory of insect
      responses to habitat heterogeneity should be based on shared traits, rather than
      a general prediction for all species.

PMID- 23881514
TI  - A validated HPLC-PDA method for identification and quantification of two
      bioactive alkaloids, ephedrine and cryptolepine, in different Sida species.
AB  - A simple, rapid, accurate and reproducible reverse-phase HPLC method has been
      developed for the identification and quantification of two alkaloids ephedrine
      and cryptolepine in different extracts of Sida species using photodiode array
      detection. Baseline separation of the two alkaloids was achieved on a Waters RP
      18 X-terra column (250 * 4.6 mm, 5 um) using a solvent system consisting of a
      mixture of water containing 0.1% Trifluoroacetic acid (TFA) and acetonitrile in a
      gradient elution mode with detection at 210 and 280 nm for ephedrine and
      cryptolepine, respectively. The calibration curves were linear in a concentration
      range of 10-250 ug/mL for both the alkaloids with correlation coefficient values
      >0.99. The limits of detection and quantification for ephedrine and cryptolepine
      were 5 and 10 ug/mL and 2.5 and 5 ug/mL, respectively. Relative standard
      deviation values for intra-day and inter-day precision were 1.22 and 1.04% for
      ephedrine and 1.71 and 2.06% for cryptolepine, respectively. Analytical recovery
      ranged from 92.46 to 103.95%. The developed HPLC method was applied to identify
      and quantify ephedrine and cryptolepine in different extracts of Sida species.

PMID- 23881515
TI  - Effectiveness of psychoeducational support on quality of life in early-stage
      breast cancer patients: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - PURPOSE: Most breast cancer patients receive psychosocial support interventions.
      However, the effectiveness of these interventions has not yet been clarified.
      Quality of life (QOL) was an important construct that should be considered when
      assessing these interventions. The purpose was to evaluate the effectiveness of
      psychosocial and especially psychoeducational support interventions for early
      stage breast cancer patients since the follow-up was bound up to 6 months after
      finishing the intervention. METHODS: We conducted a systematic review and meta
      analysis to identify randomized controlled trials with early-stage breast cancer
      patients receiving psychosocial (psychoeducational and other) support in which
      QOL was measured as a treatment outcome. We compared mean differences at less
      than 6 months post-intervention with a control group. The primary outcome was
      Global Health Status/QOL scale (Global QOL), and secondary outcomes were the
      subscales of QOL. RESULTS: No significant effect was observed for Global QOL;
      however, individuals receiving psychosocial support scored higher on the Breast
      Cancer Symptoms subscale. For psychoeducational support in the psychosocial
      support, significant effect was observed on the Emotional subscale. CONCLUSIONS:
      Our analysis strengthens the evidence of the effectiveness of psychosocial
      support in improving breast cancer symptoms and psychoeducational support in
      improving emotional well-being within 6 months post-intervention.

PMID- 23881516
TI  - Quality of life in female cancer survivors: is it related to ovarian reserve?
AB  - PURPOSE: The purpose of the study is to assess the quality-of-life scores and
      possible association with measures of ovarian reserve in female cancer survivors
      compared to healthy controls of similar age. METHODS: In this prospective cohort
      study, fifty-nine cancer survivors aged 16-39 years and 66 healthy, similarly
      aged unexposed women were recruited at the University of Pennsylvania. The
      primary outcome measures are the generic and cancer-specific domain scores on the
      Quality of Life in Adult Cancer Survivors (QLACS) instrument, early follicular
      phase serum hormones, follicle-stimulating hormone (FSH), luteinizing hormone
      (LH), estradiol (E2), inhibin B (INH), anti-Mullerian hormone (AMH), and ovarian
      ultrasound measurements [ovarian volume and antral follicle count (AFC)].
      RESULTS: Cancer survivors had significantly higher total and cancer-specific
      domain scores compared to unexposed participants. Serum AMH, INH, ovarian volume,
      and AFC were lower while serum FSH was higher in cancer survivors. Although
      survivors exhibited diminished ovarian reserve, these markers were not
      independently associated with total QLACS score. Cancer survivors with irregular
      menstrual function were found to have lower quality-of-life (QOL) scores than
      those with regular cycles. CONCLUSIONS: We found that QOL appears to be
      significantly impaired in cancer survivors compared to controls, even when remote
      from initial cancer diagnosis. In addition, our study suggests that reproductive
      aging contributes to QOL in the setting of irregular menses and likely profound
      impairment of ovarian function.

PMID- 23881517
TI  - One- and two-dimensional high-performance thin-layer chromatography as an
      alternative analytical tool for investigating polyphenol-protein interactions.
AB  - INTRODUCTION: Polyphenols and simple phenolic compounds are able to react with
      other food constituents during processing and storage. In the past, it has been
      shown that their reaction with proteins can lead to changes of the
      technofunctional or even physiological properties of both compound classes.
      However, identification of specific binding sites of small molecules within a
      protein sequence (and the corresponding conformational position) is still
      challenging. OBJECTIVE: Investigating the reaction between different food
      proteins and phenolic compounds in alkaline medium with one- and two-dimensional
      high-performance thin-layer chromatography (HPTLC) coupled to matrix-assisted
      laser desorption/ionisation (MALDI) with time-of-flight (TOF) MS for analysing
      the peptide profiles after tryptic digestion. METHODS: After modification with
      phenolic compounds, protein derivatives were digested and peptides were separated
      with one- and two-dimensional HPTLC. Peptide profiles were detected with visible
      and UV wavelengths as well as with fluorescamine, ninhydrin and 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid staining. In order to perform mass
      spectrometric measurements, peptides separated in the first dimension were
      analysed by MALDI/TOF/MS. RESULTS: Results show that the phenolic acids applied
      in this study show different specificity and susceptibility when modifying
      proteins resulting in changes of the peptide profiles, peptide quantity,
      polarity, UV-activity, radical-scavenging activity and molecular mass.
      CONCLUSION: One- and two-dimensional HPTLC supported by mass spectrometric
      detection represents an innovative, alternative tool for investigating and
      understanding polyphenol-protein interactions. This approach enables the
      identification of binding sites inside the protein chain and contributes to
      understanding the mechanism of polyphenol-protein interactions in vitro and in
      vivo.

PMID- 23881518
TI  - Colistin bladder instillation, an alternative way of treating multi-resistant
      Acinetobacter urinary tract infection: a case series and review of literature.
AB  - The multiresistant Acinetobacter species bacteria are frequently involved in
      urinary or respiratory tract infections, and one of the most effective drugs,
      colistine, is associated with significant nephrotoxicity and neurotoxicity. Given
      that very high concentrations of colistine into biological fluids are safe for
      the human organism, attempts have been made at delivering the drug topically, by
      aerosol, or, occasionally, intratechally or intraventricularly for meningitis.
      These topical treatments could eradicate the Pseudomonas sp. from the lung of
      patients with cystic fibrosis or bronchiectasis and the Acinetobacter baumannii
      from lung and meninges. However, only one case of colistin topic treatment in
      urinary tract infection is described. We report a case series of three patients
      successfully undergone colistin bladder instillations for multi drug resistant
      Acinetobacter urinary tract infection, and we review the literature about
      colistin topic treatment. 

PMID- 23881519
TI  - Regression of oral Kaposi's sarcoma after combination antiretroviral therapy.

PMID- 23881520
TI  - Two-year follow-up of a randomized controlled trial of stepped care cognitive
      behavioral therapy to prevent recurrence of depression in an older population.
AB  - OBJECTIVE: This study aims to determine the long-term effect of a stepped care
      cognitive behavioral therapy prevention program for depression in older people
      and the factors predicting or moderating outcome. METHODS: In a randomized
      controlled trial, 136 participants, aged 55 years or older, who had been treated
      for depression, received during 12 months a stepped care program (SCP) or care as
      usual (CAU) and were then followed up for a second year. Outcome was defined as
      the start of a new mental health treatment for depression in a specialized
      outpatient setting, as recorded in the patients' electronic medical records.
      RESULTS: Of the 123 patients, 38 required new mental health treatment. Survival
      analysis showed that participants in SCP (n = 27) required new treatment
      significantly more than patients receiving CAU (n = 11). Negative life events in
      the last year were predictive for new treatment in CAU but not in SCP.
      CONCLUSIONS: An SCP seems to lower the threshold for new specialized mental
      health treatment for depression, whereas new treatment in CAU patients occurs
      more often in reaction to recent life events.

PMID- 23881521
TI  - Influence of cultivar and culture system on nutritional and organoleptic quality
      of strawberry.
AB  - BACKGROUND: Strawberries are widely appreciated and consumed as a pleasant
      tasting fruit either in fresh form or as processed product. Of the many factors
      which can affect the quality of fruit (sensorial and nutritional), the cultivar
      is especially important, but it is also affected by crop conditions. The main
      characteristics related to the fruit quality and nutritional attributes were
      assessed in several varieties of strawberry grown in soilless and soil culture.
      The effect of different cultivars and cropping systems on selected quality
      parameters, were assessed by applying multivariate statistical methods, such as
      principal component analysis and partial least square discriminant analysis (PLS
      DA). RESULTS: Differences among cultivars were observed based on the mineral
      composition and glucose and fructose concentrations in both cultivation systems.
      However, no significant differences between cultivars were detected in sourness.
      Tamar and Camarosa were the sweetest cultivars among those grown in soilless and
      soil system, respectively. Both varieties also had the highest total sugars/total
      acids ratio. The comparison between strawberries cultivated in soil and soilless
      systems also revealed significant differences in the mineral composition, content
      of sugars and related parameters. CONCLUSION: Good discrimination was observed
      between cultivars of conventional crops, whereas no clear separation between
      cultivars grown in the soilless system was achieved by PLS-DA. PLS-DA also
      allowed differentiation of samples by type of crop (soilless vs. conventional
      crop). This information could be useful for selection of growing conditions and
      high-quality cultivars.

PMID- 23881522
TI  - Exosomal pMHC-I complex targets T cell-based vaccine to directly stimulate CTL
      responses leading to antitumor immunity in transgenic FVBneuN and HLA-A2/HER2
      mice and eradicating trastuzumab-resistant tumor in athymic nude mice.
AB  - One of the major obstacles in human epidermal growth factor receptor 2 (HER2)
      specific trastuzumab antibody immunotherapy of HER2-positive breast cancer is the
      development of trastuzumab resistance, warranting the search for other
      therapeutic strategies. Using mouse models, we previously demonstrated that
      ovalbumin (OVA)-specific dendritic cell (DC)-released exosome (EXOOVA)-targeted
      CD4(+) T cell-based (OVA-TEXO) vaccine stimulates efficient cytotoxic T
      lymphocyte (CTL) responses via exosomal peptide/major histocompatibility complex
      (pMHC)-I, exosomal CD80 and endogenous IL-2 signaling; and long-term CTL memory
      by means of via endogenous CD40L signaling. In this study, using two-photon
      microscopy, we provide the first visual evidence on targeting OVA-TEXO to cognate
      CD8(+) T cells in vivo via exosomal pMHC-I complex. We prepared HER2/neu-specific
      Neu-TEXO and HER2-TEXO vaccines using adenoviral vector (AdVneu and AdVHER2)
      transfected DC (DCneu and DCHER2)-released EXOs (EXOneu and EXOHER2), and
      assessed their stimulatory effects on HER2/neu-specific CTL responses and
      antitumor immunity. We demonstrate that Neu-TEXO vaccine is capable of
      stimulating efficient neu-specific CTL responses, leading to protective immunity
      against neu-expressing Tg1-1 breast cancer in all 6/6 transgenic (Tg) FVBneuN
      mice with neu-specific self-immune tolerance. We also demonstrate that HER2-TEXO
      vaccine is capable of inducing HER2-specific CTL responses and protective
      immunity against transgene HLA-A2(+)HER2(+) BL6-10A2/HER2 B16 melanoma in 2/8
      double Tg HLA-A2/HER2 mice with HER2-specific self-immune tolerance. The
      remaining 6/8 mice had significantly prolonged survival. Furthermore, we
      demonstrate that HER2-TEXO vaccine stimulates responses of CD8(+) T cells capable
      of not only inducing killing activity to HLA-A2(+)HER2(+) BL6-10A2/HER2 melanoma
      and trastuzumab-resistant BT474A2 breast cancer cells in vitro but also
      eradicating 6-day palpable HER2(+) BT474A2 breast cancer (3-4 mm in diameter) in
      athymic nude mice. Therefore, the novel T cell-based HER2-TEXO vaccine may
      provide a new therapeutic alternative for women with HER2(+) breast cancer,
      especially for trastuzumab-resistant HER2(+) breast cancer patients. 

PMID- 23881523
TI  - Rates and predictors of consideration for adjuvant radiotherapy among high-risk
      breast cancer patients: a cohort study.
AB  - Radiotherapy (RT) after breast conserving surgery (BCS) represents the standard
      for local control of breast cancer (BC). However, variations in practice persist.
      We aimed to characterize the rate of RT consideration (or referral) after BCS and
      identify predictors in Quebec, Canada, where universal health insurance is in
      place. A historical prospective cohort study using the provincial hospital
      discharge and medical services databases was conducted. All women with incident,
      non-metastatic BC (stages I-III) undergoing BCS (1998-2005) were identified. Odds
      ratios (ORs) and 95 % confidence intervals (CIs) for RT consideration were
      estimated with a generalized estimating equations regression model, adjusting for
      clustering of patients within physicians. Of the 27,483 women selected, 90 % were
      considered for RT and 84 % subsequently received it. Relative to women 50-69
      years old, younger and older women were less likely to be considered: ORs of 0.82
      (95 % CI 0.73-0.93) and 0.10 (0.09-0.12), respectively. Emergency room visits and
      hospitalizations unrelated to BC were associated with decreased odds of RT
      consideration: 0.85 (0.76-0.94) and 0.83 (0.71-0.97). Women with regional BC
      considered for chemotherapy were more likely to be considered for RT: 3.41 (2.83
      4.11). RT consideration odds increased by 7 % (OR of 1.07, 95 % CI 1.03-1.10) for
      every ten additional BCSs performed by the surgeon in the prior year. Social
      isolation, comorbidities, and greater distance to a referral center lowered the
      odds. Demographic and clinical patient-related risk factors, health service use,
      gaps in other aspects of BC management, and surgeon's experience predicted RT
      consideration. 

PMID- 23881524
TI  - Dynamic changes in high and low mammographic density human breast tissues
      maintained in murine tissue engineering chambers during various murine peripartum
      states and over time.
AB  - Mammographic density (MD) is a strong heritable risk factor for breast cancer,
      and may decrease with increasing parity. However, the biomolecular basis for MD
      associated breast cancer remains unclear, and systemic hormonal effects on MD
      associated risk is poorly understood. This study assessed the effect of murine
      peripartum states on high and low MD tissue maintained in a xenograft model of
      human MD. Method High and low MD human breast tissues were precisely sampled
      under radiographic guidance from prophylactic mastectomy specimens of women. The
      high and low MD tissues were maintained in separate vascularised biochambers in
      nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum
      involution or lactation for three additional weeks. High and low MD biochamber
      material was harvested for histologic and radiographic comparisons during various
      murine peripartum states. High and low MD biochamber tissues in nulliparous mice
      were harvested at different timepoints for histologic and radiographic
      comparisons. Results High MD biochamber tissues had decreased stromal (p =
      0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue
      areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p
      = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in
      high MD biochamber tissues during lactation. A difference in radiographic density
      was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004)
      between nulliparous, pregnant and involution groups. No differences in tissue
      composition were observed in high or low MD biochamber tissues maintained for
      different durations, although radiographic density increased over time.
      Conclusion High MD biochamber tissues had measurable histologic changes after
      postpartum involution or lactation. Alterations in radiographic density occurred
      in biochamber tissues between different peripartum states and over time. These
      findings demonstrate the dynamic nature of the human MD xenograft model,
      providing a platform for studying the biomolecular basis of MD-associated cancer
      risk. 

PMID- 23881525
TI  - High carbonate level of apatite in kidney stones implies infection, but is it
      predictive?
AB  - The presence of infectious microorganisms in urinary stones is commonly inferred
      from stone composition, especially by the presence of struvite in a stone. The
      presence of highly carbonated apatite has also been proposed as a marker of the
      presence of bacteria within a stone. We retrospectively studied 368 patients who
      had undergone percutaneous nephrolithotomy (PCNL), and who also had culture
      results for both stone and urine. Urine culture showed no association with stone
      mineral content, but stone culture was more often positive in struvite-containing
      stones (73 % positive) and majority apatite stones (65 %) than in other stone
      types (54 %, lower than the others, P < 0.02). In 51 patients in whom the
      carbonate content of apatite could be measured, carbonate in the apatite was
      weakly predictive of positive stone culture with an optimal cutoff value of 13.5
      % carbonate (sensitivity 0.61, specificity 0.80). In positive cultures of stones
      (all mineral types combined), organisms that characteristically produce urease
      were present in 71 % of the cases, with no difference in this proportion among
      different types of stone. In summary, the type of mineral in the stone was
      predictive of positive stone culture, but this correlation is imperfect, as over
      half of non-struvite, non-apatite stones were found to harbor culturable
      organisms. We conclude that mineral type is an inadequate predictor of whether a
      stone contains infectious organisms, and that stone culture is more likely to
      provide information useful to the management of patients undergoing PCNL. 

PMID- 23881526
TI  - Peak-power estimation equations in 12- to 16-year old children: comparing linear
      with allometric models.
AB  - This study examined the efficacy of peak-power estimation equations in children
      using force platform data and determined whether allometric modeling offers a
      sounder alternative to estimating peak power in pediatric samples. Ninety one
      boys and girls aged 12-16 years performed 3 countermovement jumps (CMJ) on a
      force platform. Estimated peak power (PP(est)) was determined using the Harman et
      al., Sayers SJ, Sayers CMJ, and Canavan and Vescovi equations. All 4 equations
      were associated with actual peak power (r = 0.893-0.909, all p < .01). There were
      significant differences between PP(est) using the Harman et al., Sayers SJ, and
      Sayers CMJ equations (p < .05) and actual peak power (PP(actual)). ANCOVA also
      indicated sex and age effect for PPactual (p < .01). Following a random two
      thirds to one-third split of participants, an additive linear model (p = .0001)
      predicted PPactual (adjusted R(2) = .866) from body mass and CMJ height in the
      two-thirds split (n = 60). An allometric model using CMJ height, body mass, and
      age was then developed with this sample, which predicted 88.8% of the variance in
      PP(actual) (p < .0001, adjusted R(2) = .888). The regression equations were cross
      validated using the one-third split sample (n = 31), evidencing a significant
      positive relationship (r = .910, p = .001) and no significant difference (p =
      .151) between PP(actual) and PP(est) using this equation. The allometric and
      linear models determined from this study provide accurate models to estimate peak
      power in children.

PMID- 23881527
TI  - Legal controls on cannabimimetics: an international dilemma?
AB  - Since early 2009, over 80 illicitly produced synthetic cannabinoid receptor
      agonists have been notified to the European Monitoring Centre for Drugs and Drug
      Addiction (EMCDDA). Yet more have been reported in other countries or offered for
      sale on websites. These cannabinoids typically act as agonists at CB1 receptors,
      and mimic the effects of Delta(9)-tetrahydrocannabinol (THC), the principal
      psychoactive constituent of Cannabis L. As with other 'new psychoactive
      substances', they have shown the limitations of current drug control procedures.
      First, the regular appearance of new compounds makes specific listing impractical
      and overwhelms any attempt to create risk assessments on a substance-by-substance
      basis. Secondly, the lack of human pharmacological and toxicological data hinders
      any objective attempt to show that synthetic cannabinoids are harmful. The UK has
      had a long experience of using generic legislation to control groups of
      compounds. However, cannabimimetic activity arises in a large number of distinct
      chemical families, and it is clear that generic control can no longer cope with
      this diversity whilst remaining intelligible to non-chemists. Analogue control
      presents further difficulties, and does not appear to offer an acceptable
      solution. For these reasons, legislatures in many countries are creating novel
      forms of regulation separate from domestic drug laws. The generic definition of
      classical cannabinoids, introduced into the UK Misuse of Drugs Act in 1971, also
      shows signs of weakness. Thus the growing interest in the clinical potential of
      tetrahydrocannabivarin (THCV) is inhibited, at least in the UK, by its unintended
      status as a Schedule 1 substance.

PMID- 23881528
TI  - Continuous production of flexible fibers from transgenically produced honeybee
      silk proteins.
AB  - Flexible and solvent stable fibers are produced after concentrated recombinant
      honeybee protein solutions are extruded into a methanol bath, dried, drawn in
      aqueous methanol, then covalently cross-linked using dry heat. Proteins in
      solution are predominantly coiled coil. Significant levels of non-orientated beta
      sheets form during drying or after coagulation in aqueous methanol. Drawing
      generally aligns the coiled coil component parallel with the fibre axis and beta
      sheet component perpendicular to the fiber axis. The fibres are readily handled,
      stable in the strong protein denaturants, urea and guanidinium, and suitable for
      a range of applications such as weaving and knitting. 

PMID- 23881530
TI  - Distal femur nonunion patients can expect good outcomes.
AB  - The purpose of this study is to describe our experience with distal femur
      nonunions and to report on the functional recovery of patients treated for these
      injuries. Twenty-two patients with an established distal femur nonunion were
      identified and followed prospectively. Results were compared with a control group
      consisting of 18 similar patients who had sustained an acute distal femur
      fracture. Compared with acute fracture patients, patients with a nonunion were
      more likely to have had an open fracture at initial injury (p = 0.02) and
      required a longer time to heal after final surgery (p = 0.054). No demographic
      variables were found to be predictive of complications, Short Musculoskeletal
      Functional Assessment scores, or time to union. These results show that patients
      with a distal femoral nonunion can expect to attain similar ultimate outcomes to
      patients receiving treatment for an acute distal femur fracture. Unlike the
      development of nonunions following other types of fracture, such as the hip,
      distal femur nonunions do not portend poor functional outcomes as long as bone
      union is achieved.

PMID- 23881531
TI  - "When you walk in the rain, you get wet": a qualitative study of Ghanaian
      immigrants' perspective on the epidemiological paradox.
AB  - This study sought to understand the perceptions of Ghanaian immigrants of the
      health status and health trajectory of their community. We conducted focus groups
      and interviews with 63 primarily Ghanaian immigrants living in New York City.
      Nearly all participants observed that Ghanaians are generally healthy when they
      arrive in the US, but that their health declines over time. Participants
      identified four causes of this perceived deterioration: changes in health
      behaviors, increased stress, environmental exposures, and barriers to health
      care. Participants see themselves as being at risk for many health problems
      resulting from changes in lifestyle that follow immigration. Although some
      vulnerabilities are unique to their experience as immigrants, many of the risk
      factors they described are the same as those that affect other residents in the
      communities in which they live. 

PMID- 23881532
TI  - Development and validation of the medical social self-efficacy scale for use in
      culturally diverse communities.
AB  - This study developed a new scale, The Medical Social Self-efficacy Scale (MSSES),
      to assess social self-efficacy within a medical context for patients of diverse
      cultural and linguistic backgrounds. Validation of the MSSES with a sample of 113
      persons indicated that the scale has good internal consistency, with a Cronbach's
      alpha coefficient of .85. A factor analysis yielded two factors (confidence in
      seeking medical information, confidence in stating my view) which accounted for
      64% of the total variance. Split-half reliability of the MSSES was .84.
      Predictive validity of the MSSES and its factorial structure was found for the
      mental component summary and general health subscale of the 12-item Short-Form
      Health Survey. Evidence of concurrent validity was found with the active coping,
      planning and positive reframing subscales of the Brief COPE. Concurrent validity
      was also found for the MSSES and its factors, in regard to the emotion-focused
      coping composite subscale of the Brief COPE. The results indicate that the MSSES
      appears to be a psychometrically sound instrument.

PMID- 23881533
TI  - Filariasis in sub-Saharan immigrants attended in a health area of southern Spain:
      clinical and epidemiological findings.
AB  - Filariasis is still an endemic disease in several countries worldwide. Patients
      with mansonellosis result in only relatively mild symptoms, but these infections
      could produce many visits to health care providers. In Spain, this infection is
      imported due to the increase of immigrant population reaching our country during
      last years. The health area of the Hospital of Poniente has a rate of immigrants
      around to 20%, with a high percentage coming from sub-Saharan countries, being
      Mansonella perstans the main filarial infection in the majority of cases. In the
      protocol for the immigrants, it has been included the diagnosis of filarial
      infections in order to treat them. This manuscript describes epidemiological and
      clinical aspects of patients with this kind of infection.

PMID- 23881534
TI  - Surface treatment of dental porcelain: CO2 laser as an alternative to oven glaze.
AB  - This work tested continuous CO2 laser as a surface treatment to dental porcelain
      and compared it to oven glaze (auto-glaze) by means of roughness and color
      parameters. Three commercial veneering porcelains with different crystalline
      content were tested: VM7, VM9, and VM13. Porcelain discs (3.5 * 2.0 mm, diameter
      * height) were sintered and had one side ground by a diamond bur (45 MUm)
      simulating a chairside adjustment in a clinical office. Specimens (n = 7) were
      divided into the following groups: C--control (no treatment), G--auto-glaze
      (oven), and L--surface continuous irradiation with CO2 laser (Gem Laser,
      Coherent; lambda = 10.6 MUm). Laser was tested in three exposure times (3, 4, or
      5 min) and two irradiances (45 and 50 W/cm(2)). Roughness parameters (Ra, Rz, and
      Rpm/Rz) were measured using a rugosimeter (Surftest 301, Mitutoyo). Color
      differences (DeltaE) between the G and L groups were calculated (VITA Easyshade);
      DeltaE values up to 3.3 were considered as not perceivable. A surface analysis
      was conducted by stereomicroscopy (Olympus SZ61) and SEM (Stereoscan 440, LEO).
      Crystalline content of specimens from groups C and L (50 W/cm(2), 5 min) was
      assessed by X-ray diffraction and then compared. Surface roughness (Ra and Rz)
      observed for laser-irradiated groups was similar to G for all studied porcelains.
      Rpm/Rz ratios were near 1.0 for all groups that indicated a sharp ridge profile
      for all specimens. Only one laser condition studied (50 W/cm(2), 3 min) from VM7
      porcelain resulted in color difference (DeltaE = 3.5) to G. Specimens irradiated
      with 50 W/cm(2) for 5 min presented the smoother surface observed by SEM,
      comparable to G. X-ray diffraction data revealed an increase in leucite
      crystallite size for VM9 and VM13 porcelains after laser treatment. Regarding
      roughness, continuous CO2 laser applied on porcelain surface was as effective as
      conventional oven auto-glaze.

PMID- 23881535
TI  - Turning coacervates into biohybrid glass: core/shell capsules formed by silica
      precipitation in protein/polysaccharide scaffolds.

PMID- 23881536
TI  - Physical modification of palm kernel meal improved available carbohydrate,
      physicochemical properties and in vitro digestibility in economic freshwater
      fish.
AB  - BACKGROUND: Unavailable carbohydrates are an important limiting factor for
      utilization of palm kernel meal (PKM) as aquafeed ingredients. The aim of this
      study was to improve available carbohydrate from PKM. Different physical
      modifications including water soaking, microwave irradiation, gamma irradiation
      and electron beam, were investigated in relation to chemical composition,
      physicochemical properties and in vitro carbohydrate digestibility using
      digestive enzymes from economic freshwater fish. RESULTS: Modified methods had
      significant (P < 0.05) effects on chemical composition by decreasing crude fiber
      and increasing available carbohydrates. Improvements in physicochemical
      properties of PKM, such as water solubility, microstructure, relative
      crystallinity and lignocellulosic spectra, were mainly achieved by soaking and
      microwave irradiation. Carbohydrate digestibility varied among the physical
      modifications tested (P < 0.05) and three fish species had different abilities to
      digest PKM. Soaking was the appropriate modification for increasing carbohydrate
      digestion specifically in Nile tilapia (Oreochromis niloticus), whereas either
      soaking or microwave irradiation was effective for striped snakehead (Channa
      striata). For walking catfish (Clarias batrachus), carbohydrate digestibility was
      similar among raw, soaked and microwave-irradiated PKM. CONCLUSION: These
      findings suggest that soaking and microwave irradiation could be practical
      methods for altering appropriate physicochemical properties of PKM as well as
      increasing carbohydrate digestibility in select economic freshwater fish.

PMID- 23881537
TI  - The reporting of fidelity measures in primary prevention programmes for eating
      disorders in schools.
AB  - OBJECTIVE: The aim of this paper was to examine the extent to which controlled
      trials of face-to-face school-based primary prevention for eating disorders
      report their strategies for maintaining fidelity. METHOD: A systematic review
      located 38 articles eligible for inclusion. These studies were assessed using 18
      criteria for reporting fidelity maintenance strategies based on those recommended
      by the Treatment Fidelity Workgroup of the National Institute of Health Behavior
      Change Consortium. RESULTS: Fidelity reporting was generally poor. The studies
      reported between 22% and 56% of fidelity criteria. Detailed reporting of
      curriculum-as-usual control conditions was generally lacking, as were methods to
      ensure high-quality training and mechanisms to assess provider adherence to
      intervention protocol. DISCUSSION: Poor fidelity assessment and reporting is a
      problem in school-based primary prevention programmes for eating disorders.
      Recommendations for improving fidelity maintenance and reporting practices are
      provided.

PMID- 23881538
TI  - A murine-human chimeric IgG antibody against vascular endothelial growth factor
      receptor 2 inhibits angiogenesis in vitro.
AB  - Vascular endothelial growth factor receptor 2 (VEGFR2) has been reported to play
      an important role in angiogenesis and tumorigenesis. A murine anti-VEGFR2 mAb
      (A8H1) has been established in a previous study. To reduce the incompatibility of
      the murine mAb for human use, the chimeric anti-VEGFR2-IgG was developed by
      genetic recombination of the variable regions of the A8H1 antibody and the
      constant regions of human IgG, and was expressed in Sp2/0 cells transfected with
      the two recombinant vectors containing the heavy chain and the light chain
      regions. After screening, clone 2F12 was selected and was found to stably secrete
      the murine-human chimeric anti-VEGFR2-IgG (coded 2F12). This chimeric IgG
      maintained the specificity and the affinity of the parental murine antibody
      against VEGFR2, and effectively identified VEGFR2 expressed on the surface of
      HUVECs and BEL-7402 cells. Furthermore, the 2F12 antibody demonstrated inhibition
      of angiogenesis in vitro, such as proliferation, migration, invasion and tube
      formation of HUVECs. This murine-human chimeric IgG may be considered for further
      development as an anti-angiogenesis and anti-tumor agent. 

PMID- 23881539
TI  - Stable expression of H1C2 monoclonal antibody in NS0 and CHO cells using pFUSE
      and UCOE expression system.
AB  - From our recent publications, it was found that the deimmunization method
      (Dharshanan et al. (2012) Sci Res Essays 7:2288-2299) should be applied for the
      development of humanized anti-C2 monoclonal antibody (H1C2 mAb). However, the
      overlapping-PCR mutagenesis procedure used to insert the variable regions into
      cloning vectors was laborious and time-consuming. Additionally, the expression of
      H1C2 mAb in NS0 cells was low in static culture vessels. Therefore H1C2 mAb was
      redeveloped by deimmunization method with the following modifications in order to
      optimize the production of H1C2 mAb. First, instead of the overlapping-PCR
      mutagenesis procedure, synthetic DNA coding the variable regions were used to
      express the mAb. Second, two expression vectors, pFUSE and UCOE, were used to
      express H1C2 mAb in NS0 cells and CHO cells in order to investigate the
      combination that gave the highest number of high producing stable clones. This
      will provide the highest chance of finding clones with the requisite high
      productivity and stability required for manufacturing. We found that transfection
      of UCOE in CHO cells generated the highest number of high producing stable
      clones. To our knowledge, this is the first time that H1C2 mAb has been expressed
      in CHO cells. 

PMID- 23881540
TI  - Development and validation of a stability-indicating assay including the
      isolation and characterization of degradation products of metaxalone by LC-MS.
AB  - A stability-indicating reverse-phase high-performance liquid chromatography-mass
      spectrometric method was developed and validated for the assay of metaxalone
      through forced degradation under acidic, alkaline, photo, oxidative and peroxide
      stress conditions. Separation of degradation products was accomplished on a
      reverse-phase Phenomenex C18 (250 * 4.6 mm, 5 um) column thermostated at 25 
      degrees C using 10 mM aqueous ammonium acetate: methanol (35:65 v/v) as mobile
      phase in an isocratic mode of elution. The eluents were detected at 275 nm by
      photo diode array detector and mass detectors connected in series. Two unknown
      base hydrolysis products of metaxalone were identified and characterized as (a)
      methyl 3-(3,5-dimethylphenoxy)-2-hydroxypropylcarbamate and (b) 1-(3,5
      dimethylphenoxy)-3-aminopropan-2-ol by MS, (1)H NMR and FTIR spectroscopy. The
      method was validated as per International Conference on Harmonization guidelines
      and metaxalone was selectively determined in presence of its degradation
      impurities, demonstrating its stability-indicating nature.

PMID- 23881541
TI  - One-pot synthesis of redox-responsive polymers-coated mesoporous silica
      nanoparticles and their controlled drug release.
AB  - A versatile one-pot strategy for the preparation of reversibly cross-linked
      polymer-coated mesoporous silica nanoparticles (MSNs) via surface reversible
      addition-fragmentation chain transfer (RAFT) polymerization is presented for the
      first time in this paper. The less reactive monomer oligo(ethylene glycol)
      acrylate (OEGA) and the more reactive cross-linker N,N'
      cystaminebismethacrylamide (CBMA) are chosen to be copolymerized on the external
      surfaces of RAFT agent-functionalized MSNs to form the cross-linked polymer
      shells. Owing to the reversible cleavage and restoration of disulfide bonds via
      reduction/oxidation reactions, the polymer shells can control the on/off
      switching of the nanopores and regulate the drug loading and release. The redox
      responsive release of doxorubicin (DOX) from this drug carrier is realized. The
      protein adsorption, in vitro cytotoxicity assays, and endocytosis studies
      demonstrate that this biocompatible vehicle is a potential candidate for
      delivering drugs. It is expected that this versatile grafting strategy may help
      fabricate satisfying MSN-based drug delivery systems for clinical application. 

PMID- 23881542
TI  - Biodegradation of anthracene by a novel actinomycete, Microbacterium sp. isolated
      from tropical hydrocarbon-contaminated soil.
AB  - A novel anthracene-degrading Gram-positive actinomycete, Microbacterium sp.
      strain SL10 was isolated from a hydrocarbon-contaminated soil at a mechanical
      engineering workshop in Lagos, Nigeria. The polluted soil had an unusually high
      total hydrocarbon content of 157 g/kg and presence of various heavy metals. The
      isolate tolerated salt concentration of more than 4%. It resisted cefotaxime,
      streptomycin and ciprofloxacin, but susceptible to meropenem, linezolid and
      vancomycin. The isolate exhibited growth rate and doubling time of 0.82 days(-1)
      and 0.84 days, respectively on anthracene. It degraded 57.5 and 90.12% of
      anthracene within 12 and 21 days, respectively while the rate of anthracene
      utilization by the isolate was 4.79 mg l(-1) d(-1). To the best of our knowledge,
      this is the first report of isolation and characterization of anthracene
      degrading Microbacterium sp.

PMID- 23881543
TI  - Combination of angiographic and clinical characteristics for the prediction of
      clinical outcomes in elderly patients undergoing multivessel PCI.
AB  - BACKGROUND: Risk stratification is essential for the clinical decision-making
      process in elderly patients undergoing multivessel revascularization, since the
      optimal revascularization strategy remains subject of ongoing debate. AIMS: To
      assess the prognostic value of angiographic versus clinical characteristics for
      the prediction of a first adverse cardiac and cerebrovascular events (MACCE) (all
      cause mortality, non-fatal myocardial infarction, stroke, and target lesion
      revascularization) and to develop a combined risk model. METHODS: After
      multivessel percutaneous coronary intervention (MV-PCI), SYNTAX score and
      EuroSCORE were calculated as combined risk model in 328 elderly patients who were
      followed up for a first MACCE. RESULTS: 328 patients with a mean age of 77.5 +/-
      5.1 years were followed up for 2.7 +/- 1.5 years. A first MACCE occurred in 50.0
      % (164/328) of the patients. To improve predictability, a combined risk score
      model with receiver operating characteristic curve validated cut-off values for
      EuroSCORE (>5 %) and SYNTAX score (>25) was developed. High risk patients had a
      3.5-fold higher risk for MACCE after 3 years (HR 7.1, 95 % CI 1.9-6.5; p <
      0.001). CONCLUSIONS: For adequate risk assessment in elderly patients undergoing
      MV-PCI, consideration of both comorbidities and coronary anatomic complexity is
      essential. A combined angiographic and clinical risk score provides superior
      prediction of 3-year MACCE risk in elderly patients.

PMID- 23881544
TI  - The role of dietary proteins among persons with diabetes.
AB  - Examining the role of dietary protein and establishing intake guidelines among
      individuals with diabetes is complex. The 2013 American Diabetes Association
      (ADA) standards of care recommend an individualized approach to decision making
      with regard to protein intake and dietary macronutrient composition. Needs may
      vary based on cardiometabolic risk factors and renal function. Among individuals
      with impaired renal function, the ADA recommends reducing protein intake to 0.8
      1.0 g/kg per day in earlier stages of chronic kidney disease (CKD), and to 0.8
      g/kg per day in the later stages of CKD. Epidemiological studies suggest animal
      protein may increase risk of diabetes; however, few data are available to suggest
      how protein sources influence diabetes complications. 

PMID- 23881545
TI  - Recent economic evaluations of interventions to prevent cardiovascular disease by
      reducing sodium intake.
AB  - Excess intake of sodium, a common problem worldwide, is associated with
      hypertension and cardiovascular disease (CVD), and hypertension is a major risk
      factor for CVD. Population-wide efforts to reduce sodium intake have been
      identified as a promising strategy for preventing hypertension and CVD, and such
      initiatives are currently recommended by a variety of scientific and public
      health organizations. By reviewing the literature published from January 2011 to
      March 2013, we summarized recent economic analyses of interventions to reduce
      sodium intake. The evidence, derived from estimates of resultant blood pressure
      decreases and thus decreases in the incidence of CVD events, supports population
      wide interventions for reducing sodium intake. Both lowering the salt content in
      manufactured foods and conducting mass media campaigns at the national level are
      estimated to be cost-effective in preventing CVD. Although better data on the
      cost of interventions are needed for rigorous economic evaluations, population
      wide sodium intake reduction can be a promising approach for containing the
      growing health and economic burden associated with hypertension and its sequelae.

PMID- 23881546
TI  - Hypoglycemia as a driver of cardiovascular risk in diabetes.
AB  - Severe hypoglycemia in patients with diabetes is associated with increased risk
      of adverse cardiovascular events and death. Recent large randomized clinical
      trials in individuals with type 2 diabetes have shown that intensive glycemic
      control may result in increased mortality, and hypoglycemia has been investigated
      as a possible cause. Acute hypoglycemia is a proarrhythmic, proinflammatory, and
      prothrombotic state, and several mechanisms have been proposed to explain how
      hypoglycemia might increase cardiovascular morbidity and mortality. However, data
      from large clinical trials do not provide strong evidence to establish
      hypoglycemia as a cause of increased mortality. Severe hypoglycemia is also a
      marker of frailty and a predictor of adverse outcomes in patients with diabetes.
      Individualized therapy should be the goal in patients with diabetes to avoid
      severe hypoglycemia and any related adverse outcomes. 

PMID- 23881548
TI  - Calibration of self-reported dietary measures using biomarkers: an approach to
      enhancing nutritional epidemiology reliability.
AB  - Reports from nutritional epidemiology studies lack reliability if based solely on
      self-reported dietary consumption estimates. Consumption biomarkers are available
      for some components of diet. These can be collected in subsets of study cohorts,
      along with corresponding self-report assessments. Linear regression of (log
      transformed) biomarker values on corresponding self-report values and other
      pertinent study subject characteristics yields calibration equations for dietary
      consumption, from which calibrated consumption estimates can be calculated
      throughout study cohorts. Nutritional epidemiology disease association studies of
      enhanced reliability can be expected from analyses that relate disease risk to
      calibrated consumption estimates. Applications to the study of energy and protein
      consumption in relation to cardiovascular diseases, type 2 diabetes, and cancer
      in the Women's Health Initiative will be briefly summarized. Also, challenges
      related to variables that may either mediate or confound associations of interest
      will be described, along with the need for longitudinal biomarker and self-report
      data, and the need for additional nutritional biomarker development. 

PMID- 23881547
TI  - Nuclear reprogramming and its role in vascular smooth muscle cells.
AB  - In general terms, "nuclear reprogramming" refers to a change in gene expression
      profile that results in a significant switch in cellular phenotype. Nuclear
      reprogramming was first addressed by pioneering studies of cell differentiation
      during embryonic development. In recent years, nuclear reprogramming has been
      studied in great detail in the context of experimentally controlled
      dedifferentiation and transdifferentiation of mammalian cells for therapeutic
      purposes. In this review, we present a perspective on nuclear reprogramming in
      the context of spontaneous, pathophysiological phenotypic switch of vascular
      cells occurring in the atherosclerotic lesion. In particular, we focus on the
      current knowledge of epigenetic mechanisms participating in the extraordinary
      flexibility of the gene expression profile of vascular smooth muscle cells and
      other cell types participating in atherogenesis. Understanding how epigenetic
      changes participate in vascular cell plasticity may lead to effective therapies
      based on the remodelling of the vascular architecture. 

PMID- 23881550
TI  - Bilateral laryngoceles.

PMID- 23881549
TI  - Acetylated tubulin (AT) as a prognostic marker in squamous cell carcinoma of the
      head and neck.
AB  - Acetylated tubulin (AT) expression has been proposed as a marker for sensitivity
      to taxane chemotherapy. We wanted to explore AT as a prognostic marker in
      squamous cell carcinoma of the head and neck (SCCHN). We assessed AT expression
      in archival tissue from our institutional tissue bank of primary SCCHN specimens.
      We also examined AT expression on pre-therapy tissues of patients with SCCHN
      receiving induction chemotherapy with docetaxel, cisplatin and 5FU (TPF IC). AT
      expression was assessed on archival cases of SCCHN with (N = 63) and without (N =
      82) locoregional lymph node metastases (LNM). The predominant tumor site was oral
      cavity (52 %). Immunohistochemistry staining was based on staining intensity and
      percentage of tumor cells stained to create a weighted index (WI). A total of
      nine patients who received TPF IC were evaluable for response by RECIST and also
      had pre-therapy tissues available. A significant independent correlation between
      AT and tumor grade (p = 0.001) and primary location (p = 0.008) was noted. There
      was a trend of higher AT in patients with presence of LNM (p = 0.052) and a trend
      in improved OS for patients with an AT WI below the median compared to those
      above the median for patients with no LNM (p = 0.054). For patients treated with
      induction TPF, we observed an inverse correlation between AT expression and
      response to TPF IC (p = 0.0071). AT expression is correlated with tumor grade and
      primary site. There was an observed trend correlating AT with presence nodal
      metastases. The observed inverse correlation with response to taxane based
      chemotherapy needs validation in a larger sample size.

PMID- 23881551
TI  - Treatment of melasma with topical agents, peels and lasers: an evidence-based
      review.
AB  - BACKGROUND: Melasma is an acquired disorder of hyperpigmentation occurring on the
      face and predominantly affecting women of childbearing age. It is a chronic,
      often relapsing condition with a negative impact on quality of life. Current
      treatments for melasma are unsatisfactory. OBJECTIVE: The aim of this article was
      to conduct an evidence-based review of interventions available for the treatment
      of melasma. METHODS: A systematic literature search was performed using PubMed
      and the keywords 'melasma' or 'chloasma' in the title. The search was further
      refined by using a filter for 'controlled clinical trials' and 'randomized
      controlled trial'. The included studies were used to develop recommendations for
      treatment. RESULTS: The electronic search yielded a total of 80 citations. Forty
      studies were included in this review, which had a total of 2,912 participants.
      Three different therapeutic modalities were investigated-topical agents, chemical
      peels, and laser and light therapies. Topical depigmenting agents were found to
      be the most effective in treating moderate-to-severe melasma, with combination
      therapies, such as triple-combination therapy (hydroquinone, tretinoin, and
      fluocinolone acetonide), yielding the best results. Chemical peels as well as
      laser and light therapies were found to have moderate benefit but more studies
      are needed to determine their efficacy and long-term safety. Adverse events
      associated with treatment were mild and short-lasting and included skin
      irritation, dryness, burning, and erythema. The data could not be statistically
      pooled because of the heterogeneity of treatments and lack of consistency across
      study designs. CONCLUSIONS: Topical combination therapies were found to be more
      effective than monotherapy. Triple combination therapy was found to be the most
      effective, but approximately 40 % of patients develop erythema and peeling.
      Chemical peels and laser and light therapies produced mixed results, with
      increased risk of irritation and subsequent hyperpigmentation, particularly in
      darker-skinned individuals. Hence, current treatments available for melasma
      remain unsatisfactory. Many of the studies lacked long-term follow-up.
      Limitations of current literature include the heterogeneity of study designs,
      small sample sizes, and poor follow-up rates. Additional evidence for the effects
      and role of sunscreens is needed. Categorization or stratification of demographic
      data should also be included in future studies, such as age, melasma type, and
      duration of melasma prior to initiation of treatment. Patient's perception of
      improvement versus investigator's assessment of improvement should also be
      included in future studies and standardized methods of study design and
      assessment of outcomes are needed to form definitive conclusions on the efficacy
      of different treatment modalities.

PMID- 23881552
TI  - Structural and photoluminescence study of Mn2+-activated CaYAl3 O7 blue
      phosphors.
AB  - The structural and photoluminescence properties of CaYAl3 O7 phosphor material
      doped with varying concentration of Mn(2+) have been studied. The phosphor
      material was synthesized by the combustion method at 500  degrees C and was
      characterized using X-ray diffraction, Fourier transform infrared spectroscopy
      and photoluminescence spectroscopy (PL). X-ray diffraction showed that the
      crystallites have average sizes in the range of ~58-70 nm. Corresponding Fourier
      transform infrared spectroscopy investigations confirm the phase formation and
      the presence of aluminate group (Al-O bands) in CaYAl3 O7 :Mn(2+) phosphor. Under
      the excitation at 356 nm wavelength, the PL spectra show the occurrence of two
      emission peaks obtained in the blue region at 389 nm and 412 nm, which is
      attributed to the 4 T1(G) -> 6A1 transition of Mn(2+) ion. Upon increasing Mn(2+)
      concentration, the relative PL intensity shows an initial decrement followed by
      an increase displaying the effect of concentration quenching. Overall the results
      suggest the possibility of using this material in white lighting devices and
      plasma display panels.

PMID- 23881553
TI  - Upper and lower airways associations in patients with chronic rhinosinusitis and
      bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is an uncommon disease of the lower airways
      characterized by bronchial wall destruction and permanent bronchiolar dilation.
      Several etiologic categories exist, and patients with bronchiectasis often
      complain of symptoms suggestive of chronic rhinosinusitis (CRS). The present
      study investigates the association between bronchiectasis and CRS using
      radiologic and bacteriologic data. METHODS: Retrospective chart review from a
      tertiary care respiratory hospital was performed. Sinus computed tomography (CT)
      scans were examined for extent of disease and relationship to pulmonary disease
      severity. Statistical analysis was performed with Student t test and linear
      regression. Upper and lower airway cultures from patients with both
      bronchiectasis and CRS were compared using the chance adjusted agreement.
      RESULTS: Patients with bronchiectasis were found to have a significantly higher
      Lund-Mackay score when compared to patients with allergic rhinitis (p = 0.047).
      Lund-Mackay CT score did not correlate with forced expiratory volume in 1 second
      (FEV1 ) and FEV1 :forced vital capacity (FVC), or presence of Pseudomonas
      aeruginosa. Correlation of upper and lower airway bacterial cultures in patients
      with both bronchiectasis and CRS was noted (kappa = 0.294, p = 0.004),
      particularly when P. aeruginosa was present (kappa = 0.49, p < 0.0001).
      CONCLUSION: The current study suggests that the upper and lower airways may be
      linked in CRS and bronchiectasis from both an objective radiologic standpoint and
      a bacteriologic perspective. This finding carries implications for disease
      pathogenesis, clinical care, and future research.

PMID- 23881554
TI  - Engineered spider silk protein-based composites for drug delivery.
AB  - Silk protein-based materials are promising materials for the delivery of drugs
      and other active ingredients, due to their processability, biocompatibility, and
      biodegradability. The preparation of films composed of an engineered spider silk
      protein (eADF4(C16)) in combination with either a polyester (polycaprolactone) or
      a polyurethane (pellethane), and their physical properties are described. The
      release profiles are affected by both the film composition and the presence of
      enzymes, and release can be observed over a period of several weeks. Such silk
      based composites have potential as drug eluting biocompatible coatings or
      implantable devices. 

PMID- 23881555
TI  - Age is an independent poor prognostic factor in cutaneous head and neck melanoma.
AB  - OBJECTIVE/HYPOTHESIS: To evaluate age as an independent prognostic factor in
      cutaneous head and neck melanoma. STUDY DESIGN: Prospective case-control study.
      METHODS: We selected 12,195 patients from the Surveillance, Epidemiology, and End
      Results database with cutaneous head and neck melanoma diagnosed from 2004 to
      2009. Patients were stratified into ages 1 to 44 years, 45 to 64 years, and 65+
      years. Meanwhile, stage was stratified into early (American Joint Committee on
      Cancer [AJCC] stage I-II) versus late (AJCC stage III-IV). We calculated overall
      survival and compared it to age-matched cancer-free controls to obtain overall
      relative survival. Finally, we performed a Cox multivariate regression by age and
      stage. RESULTS: Age had a statistically significant (P < .05) stratified decrease
      in overall survival for both early- and late-stage melanoma. However, we only
      found a statistically significant (P < .05) stratified decrease in overall
      relative survival for late-stage melanoma. Early-stage melanoma had no
      statistical difference in overall relative survival between the 45 to 64 years
      group and all other age groups studied. Finally, our multivariate Cox regression
      of stage, gender, race, and age found a hazard ratio [HR] of 2.005 (95%
      confidence interval [CI]: 1.493-1.693, P < .001) for the 45 to 64 years age
      group, and an HR of 4.174 (95% CI: 3.153-5.526, P < .001) for the 65+ years age
      group. CONCLUSIONS: Age at diagnosis is a poor prognostic factor for patients
      with cutaneous head and neck carcinoma. It plays an important role in survival,
      with a linear increase in risk as age increases. This risk is clinically
      significant with patients ages 65+ years, having an HR four times the risk of
      patients 1 to 44 years old. LEVEL OF EVIDENCE: 3b.

PMID- 23881556
TI  - Diagnosis and treatment of low-grade osteosarcoma: experience with nine cases.
AB  - BACKGROUND: Low-grade osteosarcoma, including low-grade central osteosarcoma and
      parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is
      occasionally difficult. In this article we present cases of low-grade
      osteosarcomas that should be reviewed by a clinical oncologist. PATIENTS AND
      METHODS: Nine cases of histologically diagnosed Broder grade 1 osteosarcoma were
      retrospectively reviewed. The pathological diagnoses included parosteal
      osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic
      osteosarcoma in four, four, and one cases, respectively. RESULTS: Duration from
      initial surgical intervention including biopsy to final diagnosis as low-grade
      osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy
      specimens included fibrous dysplasia in three cases, chondroblastoma in one case,
      and a giant cell tumor in one case. The average number of histological
      examinations was 1.8. Low-grade osteosarcomas are well suited for biological
      reconstruction: seven cases were reconstructed by frozen autografts, distraction
      osteogenesis, or vascularized bone grafts. CONCLUSION: Low-grade osteosarcomas
      can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the
      diagnosis of a low-grade osteosarcoma is not established on the basis of
      radiologic findings, care should be exercised, even when a biopsy suggests a
      benign lesion. Low-grade osteosarcomas should be treated with wide excision, even
      after an intralesional excision. Biological reconstruction might be a better
      option for low-grade osteosarcomas.

PMID- 23881557
TI  - Overestimation of Physical Abilities Among Boys With and Without ADHD.
AB  - OBJECTIVE: Children with ADHD have been widely reported to overestimate their
      abilities in social and academic domains, but a similar overestimation of
      physical abilities has not been examined. METHOD: Twenty-four elementary school
      age boys with ADHD and fifteen boys without ADHD were compared on their ability
      to accurately estimate their ability to complete four lab-based physical tasks,
      varying on three levels of difficulty: (a) within their ability, (b) 8% beyond
      their ability, and (c) 13% beyond their ability. RESULTS: Children with ADHD were
      significantly more likely than controls to overestimate their physical ability at
      difficult levels of the task. CONCLUSION: Implications of these results for
      preventing risky behaviors in children with ADHD are discussed.

PMID- 23881558
TI  - The Effects of Preresponse Cues on Inhibitory Control and Response Time in Adults
      With ADHD.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of preresponse
      cues on behavioral control in adults with ADHD. METHOD: Eighty-eight adults with
      ADHD and 67 adults with no history of ADHD completed a cued go/no-go task. This
      task requires participants to respond or inhibit a response to go and no-go
      targets, respectively, and preresponse cues provide participants with predictive
      information about the upcoming target. RESULTS: Overall, participants with ADHD
      made more inhibitory failures and responded more slowly than controls. These
      group differences were only present in the valid-cue condition, and there were no
      significant group differences in the invalid-cue conditions. CONCLUSION: These
      findings suggest that adults with ADHD are less able to utilize predictive
      environmental information to facilitate behavioral control.

PMID- 23881559
TI  - Congruent Validity of the Strengths and Difficulties Questionnaire to Screen for
      Comorbidities in Children With ADHD.
AB  - OBJECTIVE: This study aimed to determine whether the Strengths and Difficulties
      Questionnaire (SDQ) is an effective screening tool for identifying comorbid
      mental health difficulties in children with ADHD. METHOD: Parents of children
      with ADHD (5-13 years) completed the SDQ and the Anxiety Disorders Interview
      Schedule for DSM-IV-Parent Version (ADIS-C/P-IV). Data from both the measures
      were compared to determine congruent validity. RESULTS: Analyses revealed that
      significant relationships exist between the SDQ total score and the total number
      of comorbidities on the ADIS-C/P-IV. The SDQ emotional problem and conduct
      problem scales were significantly related to internalizing and externalizing
      comorbidities on the ADIS-C/P-IV, respectively. CONCLUSION: While significant
      relationships were found between the SDQ and ADIS-C/P-IV across various domains,
      this relationship was stronger for externalizing comorbidities. Additional
      screening questions are required to effectively screen for less common
      internalizing comorbidities in children with ADHD, for example, major depression
      and panic disorder.

PMID- 23881560
TI  - Significance of Dopaminergic Gene Variants in the Male Biasness of ADHD.
AB  - OBJECTIVE: ADHD is frequently detected in boys though there is no established
      cause. One possibility is that genes predisposing to ADHD have sexually dimorphic
      effects. With an aim to find out the reason for this male biasness, contribution
      of 14 functional polymorphisms was investigated in ADHD subjects. METHOD: Genomic
      DNA of probands, their parents, and ethnically matched controls was subjected to
      analysis of single-nucleotide polymorphisms and variable number of tandem repeats
      (VNTRs). RESULTS: Case-control analysis revealed significant higher occurrence of
      DAT1 intron 8 VNTR "5R" allele ( p = .028), DBH rs1108580 "A" allele ( p = .027),
      and MAOA-u VNTR-rs6323 3R-T haplotype ( p = .007) in male probands. Family-based
      analysis showed significant preferential transmission of Dopamine receptor D4
      exon 3 VNTR-rs1800955 7R-T haplotype from parents to male probands ( p = .008).
      Interaction between DBH gene variants and low enzymatic activity was also
      noticed, especially in male probands. CONCLUSION: Data obtained may partly answer
      the male biasness of ADHD.

PMID- 23881561
TI  - [T helper cell differentiation and plasticity].

PMID- 23881562
TI  - Etifoxine stimulates allopregnanolone synthesis in the spinal cord to produce
      analgesia in experimental mononeuropathy.
AB  - BACKGROUND: Pathological pain states are often associated with neuronal
      hyperexcitability in the spinal cord. Reducing this excitability could
      theoretically be achieved by amplifying the existing spinal inhibitory control
      mediated by GABAA receptors (GABAARs). In this study, we used the non
      benzodiazepine anxiolytic etifoxine (EFX) to characterize its interest as pain
      killer and spinal mechanisms of action. EFX potentiates GABAAR function but can
      also increase its function by stimulating the local synthesis of 3alpha-reduced
      neurosteroids (3alphaNS), the most potent endogenous modulators of this receptor.
      METHODS: The efficacy of EFX analgesia and the contribution of 3alphaNS were
      evaluated in a rat model of mononeuropathy. Spinal contribution of EFX was
      characterized through changes in pain symptoms after intrathecal injections,
      spinal content of EFX and 3alphaNS, and expression of FosB-related genes, a
      marker of long-term plasticity. RESULTS: We found that a 2-week treatment with
      EFX (>5 mg/kg, i.p.) fully suppressed neuropathic pain symptoms. This effect was
      fully mediated by 3alphaNS and probably by allopregnanolone, which was found at a
      high concentration in the spinal cord. In good agreement, the level of EFX
      analgesia after intrathecal injections confirmed that the spinal cord is a
      privileged target as well as the limited expression of FosB/DeltaFosB gene
      products that are highly expressed in persistent pain states. CONCLUSIONS: This
      preclinical study shows that stimulating the production of endogenous analgesics
      such as 3alphaNS represents an interesting strategy to reduce neuropathic pain
      symptoms. Since EFX is already prescribed as an anxiolytic in several countries,
      a translation to the human clinic needs to be rapidly evaluated.

PMID- 23881563
TI  - Modulation of the thermoresponsive behavior of poly(N,N-diethylacrylamide) via
      cyclodextrin host/guest interactions.
AB  - The modulation of the cloud point of aqueous poly(N,N-diethylacrylamide)
      solutions via the formation of supramolecular cyclodextrin complexes with
      hydrophobic end groups, namely adamantyl, tert-butyl phenyl and azobenzene,
      synthesized via RAFT polymerization is described. The dependence of the apparent
      cloud points after cyclodextrin complexation is investigated with respect to the
      type and quantity of the guest end group, the polymer chain length and the
      cyclodextrin/end group ratio. Furthermore, the effect is reversed via the
      addition of guest molecules or via biocompatible enzymatic degradation of the
      cyclodextrins entire. 

PMID- 23881564
TI  - Catalytic and stereoselective ortho-lithiation of a ferrocene derivative.

PMID- 23881565
TI  - Comparing pioglitazone to insulin with respect to cancer, cardiovascular and bone
      fracture endpoints, using propensity score weights.
AB  - BACKGROUND: Diabetes is an important global disease, associated with significant
      morbidity and an increased risk of death due to chronic end-organ complications.
      The thiazolidinediones, used mainly as third-line agents in type 2 diabetes
      mellitus (T2DM), have been associated with some safety concerns, such as an
      increased risk of bladder cancer, an increased risk of bone fracture and
      heterogeneous effects on cardiovascular events. OBJECTIVE: This study aimed to
      evaluate safety data on pioglitazone for several outcomes and examine them in
      context with each other as well as with insulin, another third-line treatment for
      T2DM. METHODS: This retrospective cohort study extracted data from May 1, 2000
      until June 30, 2010, from the i3 InVision Data MartTM database. To adjust for the
      testing of multiple hypotheses, the Holm method was applied to endpoints
      representing potential harm from pioglitazone treatment, separately from those
      representing potential benefit from pioglitazone. The study population included
      patients with T2DM >= 45 years old who were new users of either pioglitazone or
      insulin. Key outcomes were incident cases of a composite of myocardial infarction
      (MI) or stroke requiring hospitalization; bone fracture requiring
      hospitalization; bladder cancer; and a composite of nine other selected cancers.
      Kaplan-Meier curves were generated and hazard ratios (HRs) for pioglitazone
      versus insulin were estimated from Cox proportional hazards models adjusted with
      inverse probability of treatment weights derived from propensity scores. RESULTS:
      A total of 56,536 patients (pioglitazone group 38,588; insulin group 17,948)
      qualified for the study. The mean follow-up was 2.2 years for pioglitazone and
      1.9 years for insulin patients. Weighted survival analysis of the composite of MI
      and stroke, as well as the composite of nine cancers, yielded significant
      differences in favour of pioglitazone. For the composite of MI and stroke, the HR
      for pioglitazone versus insulin was 0.44 (95 % confidence interval [CI] 0.39
      0.50, p < 0.0001). Modelling of the composite of nine selected cancers produced
      an HR of 0.78 (95 % CI 0.71-0.85, p < 0.0001). A non-statistically significant
      difference in favour of pioglitazone was observed in the incidence rate of bone
      fracture requiring hospitalization (HR 0.86, 95 % CI 0.74-1.01, p = 0.058). For
      bladder cancer, the overall incidence rates were relatively low and showed no
      significant difference between the two groups; the HR for pioglitazone versus
      insulin was 0.92 (95 % CI 0.63-1.33, p = 0.64). CONCLUSION: Compared with
      insulin, pioglitazone was associated with a significant reduction in the risk of
      MI and stroke requiring hospitalization, and a significant reduction in the risk
      of other selected cancers. While pioglitazone treatment may be linked with a
      lower risk of bladder cancer and bone fracture relative to insulin, these
      differences were not statistically significant.

PMID- 23881566
TI  - Safety, tolerability and pharmacokinetics and pharmacodynamics of inhaled once
      daily umeclidinium in healthy adults deficient in CYP2D6 activity: a double
      blind, randomized clinical trial.
AB  - BACKGROUND: Umeclidinium is a new, long-acting, muscarinic receptor antagonist
      currently in development for the treatment of chronic obstructive pulmonary
      disease (COPD). In vitro cell culture data suggest that up to 99 % of
      umeclidinium is potentially metabolized by cytochrome P450 2D6 (CYP2D6), but
      without a definitive human metabolism radiolabel study, the extrapolation of in
      vitro to in vivo is only an estimate. OBJECTIVE: The objective of this study was
      to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of
      umeclidinium in patients with normal and deficient CYP2D6 metabolism. METHODS:
      This was a randomized, placebo-controlled study to assess the safety,
      tolerability, pharmacokinetics and pharmacodynamics of inhaled single and repeat
      doses (for 7 days) of umeclidinium. The study took place at a single clinical
      site, at which subjects remained throughout the study. Healthy volunteers (HVTs)
      who were normal CYP2D6 metabolizers (HVT-NMs) [n = 20] and poor CYP2D6
      metabolizers (HVT-PMs) [n = 16] participated in the study. The subjects received
      umeclidinium (100-1,000 MUg) and placebo as single and repeat doses. The primary
      outcome measurements were protocol-defined safety and tolerability endpoints.
      RESULTS: Thirteen subjects in each population reported adverse events (AEs); none
      were considered serious. No clinically significant abnormalities in vital signs,
      lung function, haematology, biochemistry, 12-lead electrocardiograms (ECGs) or 24
      h Holter ECGs were attributable to the study drug. There were no differences in
      plasma and urine pharmacokinetics between populations: the plasma area under the
      concentration-time curve over the dosing interval (from 0 to 24 h for the once
      daily drug) [AUC(tau) (ng.h/mL)] and the maximum plasma concentration [C(max)
      (ng/mL)] ratios (with 90 % confidence intervals [CIs]) following repeat dosing
      with 500 MUg umeclidinium for HVT-PMs (as compared with HVT-NMs) were 1.03 (0.79
      1.34) and 0.80 (0.59-1.08), respectively; the cumulative amount of the unchanged
      drug excreted into the urine at 24 h (Ae(24)) [ng] ratio was 1.01 (0.82-1.26).
      Following repeat dosing with umeclidinium 1,000 MUg, the plasma AUC(tau)
      [ng.h/mL] and C(max) (ng/mL) ratios (with 90 % CIs) were 1.33 (0.98-1.81) and
      1.07 (0.76-1.51); the urine Ae(24) (ng) ratio was 1.47 (1.15-1.88). Similar
      ratios for urine and plasma were observed following single and repeat-dose
      regimens. CONCLUSION: Umeclidinium has favourable safety and pharmacokinetic
      profiles in both HVT-NM and HVT-PM populations.

PMID- 23881567
TI  - Efficacy and safety of sublingual fentanyl orally disintegrating tablets in
      patients with breakthrough pain: multicentre prospective study.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the
      effectiveness and safety of sublingual fentanyl oral disintegrating tablets
      (sublingual fentanyl ODT) for the treatment of breakthrough pain (BTP), cancer or
      non-cancer related, in terms of relief of pain intensity, adverse events (AEs)
      and patient satisfaction, and to further examine the clinical and epidemiological
      profile of patients with BTP in a clinical setting. METHODS: A multicentre,
      prospective, open-label study was conducted in 19 pain units from Catalonia
      hospitals (Spain) over a 1-month period. Opioid-tolerant adult patients
      experiencing episodes of BTP intensity >5 on a visual analogue scale (VAS) during
      the 12-24 h before screening or AEs related to their previous rescue medication
      for BTP received sublingual fentanyl ODT in the course of routine clinical
      practice and completed a 30-day study period consisting of five assessment
      points: days 0 (baseline), 3, 7, 15 and 30. The efficacy was assessed by
      collecting pain intensity and pain relief data at baseline and at each
      assessment. AEs were recorded by investigators throughout the study during clinic
      visits and telephone follow-ups. For all patients, titration was begun with an
      initial dose of 100 MUg. No more than two doses were allowed to treat an episode
      and patients might wait at least 4 h before treating another BTP episode with
      sublingual fentanyl ODT. The dose was increased by 100 MUg multiples up to 400
      MUg as needed; and by 200 MUg multiples up from 400 to 800 MUg, the maximum
      titration step. RESULTS: A total of 182 patients were enrolled and 177 (97.2 %)
      completed the study: 37 had breakthrough cancer pain (BTcP) and 145 had
      breakthrough non-cancer pain (BTncP). The mean pain intensity showed a
      statistically significant improvement at the first assessment point and at all
      assessments thereafter (p < 0.0001). At the end of the study, the time lag
      between administration and first effect of sublingual fentanyl ODT was <=10 min
      in 69.0 % (60 % BTcP and 71.2 % BTncP). The number of daily BTP episodes
      decreased in both groups, but it was statistically significant in BTcP. 114
      patients (62.64 %) experienced AEs during the study. AEs recorded included
      nausea, vomiting, somnolence and constipation, and seven (4.49 %) were considered
      severe. No death or discontinuation was considered related to AEs. CONCLUSION:
      Sublingual fentanyl ODT provided rapid and consistent relief from BTP, both in
      cancer and non-cancer patients. It was well-tolerated and well-accepted by
      patients in routine clinical practice.

PMID- 23881568
TI  - Fixed-dose ibuprofen/famotidine: a review of its use to reduce the risk of
      gastric and duodenal ulcers in patients requiring NSAID therapy.
AB  - A fixed-dose combination of the nonsteroidal anti-inflammatory drug (NSAID)
      ibuprofen and the histamine H(2) receptor antagonist famotidine
      (ibuprofen/famotidine; DUEXIS((r))) is now available for the symptomatic
      treatment of arthritic symptoms and to reduce the risk of upper gastrointestinal
      (GI) ulcers in patients who require ibuprofen therapy. The gastroprotective
      efficacy of oral ibuprofen/famotidine 800/26.6 mg three times daily in patients
      requiring NSAID therapy for inflammatory conditions and/or pain was evaluated in
      two 24-week, well-designed trials (REDUCE-1 and -2). According to the post
      adjudication analysis of these studies, ibuprofen/famotidine significantly
      reduced the life table estimated rate of gastric ulcers (primary endpoint of
      REDUCE-1) but not upper GI ulcers (i.e. gastric or duodenal ulcers) [primary
      endpoint of REDUCE-2] compared with ibuprofen alone. When life table estimated
      rates of secondary endpoints were assessed, significantly fewer recipients of the
      fixed-dose combination than of ibuprofen alone developed upper GI ulcers or
      duodenal ulcers in REDUCE-1, whereas the between-group difference in gastric
      ulcers and duodenal ulcers was considered to be nonsignificant in REDUCE-2
      because of hierarchical testing. However, in a prespecified pooled analysis of
      REDUCE-1 and -2, the rate of upper GI ulcers as well as each of the upper GI
      ulcer components was significantly lower with ibuprofen/famotidine than with
      ibuprofen. Ibuprofen/famotidine was generally well tolerated, with a tolerability
      profile consistent with those established for the individual agents.

PMID- 23881569
TI  - Histomorphometric and immunohistochemical study of the goat abomasum during
      prenatal development.
AB  - This study sought to chart the morphological changes taking place in the goat
      abomasum during prenatal development, using histomorphometric and
      immunohistochemical techniques. A total of 140 goat embryos and fetuses, from the
      first stages of prenatal life until birth. Differentiation of the abomasum as a
      separate compartment of the primitive gastric tube was observed at 35 days of
      prenatal life (CRL 3 cm, 23% gestation). Primitive abomasal folds were first
      observed at 38 days (CRL 4.3 cm, 25% gestation). The muscularis mucosae was
      visible by 64 days (CRL 13.5 cm, 43% gestation). Transformation of
      pseudostratified epithelium to simple cylindrical epithelium was also observed at
      this stage. Differentiation of gastric pits and glands first became apparent at
      75 days (CRL 17.5 cm, 50% gestation) and 84 days (CRL 20 cm, 55% gestation),
      respectively. Neuroendocrine cells were detected by synaptophysin (SYP) at 64
      days (CRL 13.5 cm, 43% gestation), while glial cell markers (glial fibrillary
      acidic protein - GFAP, and vimentin-VIM) were observed at 64 days (CRL 13.5 cm,
      43% gestation) and 38 days (CRL 4.3 cm, 25% gestation), respectively.
      Neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) were detected at
      75 days (CRL 17.5 cm, 50% gestation). Gastrin-immunoreactive cells first appeared
      in the abomasum at 76 days (CRL 18 cm, 50% gestation). In conclusion, prenatal
      development of the abomasum appears to take place somewhat earlier in goats than
      in sheep or cattle, but at a similar rate to that reported in wild ruminants such
      as deer.

PMID- 23881570
TI  - More than words: fast acquisition and generalization of orthographic regularities
      during novel word learning in adults.
AB  - In literates, reading is a fundamental channel for acquiring new vocabulary both
      in the mother tongue and in foreign languages. By using an artificial language
      learning task, we examined the acquisition of novel written words and their
      embedded regularities (an orthographic surface feature and a syllabic feature) in
      three groups of university students with different exposures (Group 1 saw 2 words
      once, Group 2 saw 20 words once, Group 3 saw 20 words three times). Recognition
      memory results for Groups 2 and 3 indicated that adults can learn novel written
      words even with just a single exposure, albeit repeated exposure improved target
      detection. A generalization task revealed that even the minimal exposure in Group
      1 was enough for acquisition of the two embedded regularities. More exemplars and
      repeated exposure provided more robust effects for the syllable regularity.
      Finally, post-test interview showed that repeated exposure was needed to become
      aware of the regularities. The present results show that adults learn novel
      written words and their inherent regularities in a fast and effective fashion. 

PMID- 23881571
TI  - Synthesis of a strained acetylenic macrocycle incorporating a para
      oligo[2]cruciform bridge bent over nanoscopic dimensions: structural, electronic,
      spectroscopic, and ion-sensing properties.
AB  - An Eglinton-Galbraith diethyne cyclization preferentially yielded a structurally
      unusual macrocycle, comprising a strained conjugated oligo[2]cruciform wire,
      forced into a 2.2 nm bow-shape by a terpyridine rein or tether, and stabilized
      towards light and heat by four insulating triisopropylsilylacetylene (TIPSA)
      substituents. Spectroscopic ion-binding studies revealed the macrocycle to
      exhibit a particularly high UV/Vis selectivity for Pd(II) in dilute solution, and
      one of its precursors to afford a variety of luminescence quenching and color
      responses to particular metals, suggestive of promising ion-sensor applications.
      Under more concentrated conditions, the new macrocycle is able to bind specific
      metals (e.g., Au(I)) within its cavity despite the steric constraints.
      Intriguingly, variable-temperature (VT) UV/Vis/(1)H NMR investigations showed the
      TIPSA substituents to undergo restricted intramolecular motions along with
      reversible changes in the spectroscopic bandgap of the compound with temperature.
      In line with the theoretical calculations, the VT UV/Vis observations are
      consistent with a thermal modulation of the electronic conjugation through the
      strained oligo[2]cruciform bridge, which is coupled with redistributions within a
      mixture of conformational isomers of the macrocycle with differing relative
      twisting between the TIPSA-substituted phenyl rings. Overall, the generation of a
      para-oligo[2]cruciform, bent and flexed over nanoscopic dimensions through
      conformational tethering within the macrocyclic ring is noteworthy, and suggests
      a general approach to nanosized, curved, and strained, yet heat- and light
      stable, para-phenyleneethynylene oligomers with unique physicochemical properties
      and challenging theoretical possibilities.

PMID- 23881572
TI  - Three-dimensional sinus imaging as an adjunct to two-dimensional imaging to
      accelerate education and improve spatial orientation.
AB  - OBJECTIVES/HYPOTHESIS: Develop a novel three-dimensional (3-D) anatomical model
      to assist in improving spatial knowledge of the skull base, paranasal sinuses,
      and adjacent structures, and validate the utilization of 3-D reconstruction to
      augment two-dimensional (2-D) computed tomography (CT) for the training of
      medical students and otolaryngology-head and neck surgery residents. STUDY
      DESIGN: Prospective study. METHODS: A study of 18 subjects studying sinus anatomy
      was conducted at a tertiary academic center during the 2011 to 2012 academic
      year. An image processing and 3-D modeling program was used to create a color
      coded 3-D scalable/layerable/rotatable model of key paranasal and skull base
      structures from a 2-D high-resolution sinus CT scan. Subjects received
      instruction of the sinus anatomy in two sessions, first through review of a 2-D
      CT sinus scan, followed by an educational module of the 3-D reconstruction. After
      each session, subjects rated their knowledge of the sinus and adjacent structures
      on a self-assessment questionnaire. RESULTS: Significant improvement in the
      perceived understanding of the anatomy was noted after the 3-D educational module
      session when compared to the 2-D CT session alone (P < .01). Every subject
      believed the addition of 3-D imaging accelerated their education of sinus anatomy
      and recommended its use to others. CONCLUSIONS: The impression of the learners
      was that a 3-D educational module, highlighting key structures, is a highly
      effective tool to enhance the education of medical students and otolaryngology
      residents in sinus and skull base anatomy and its adjacent structures,
      specifically in conceptualizing the spatial orientation of these structures.

PMID- 23881573
TI  - A colorimetric and fluorescent probe for fluoride ions based on 6-acetyl-2
      naphthol.
AB  - A colorimetric and turn-on fluorescent probe for fluoride ions, tert
      butyldimethylsilane 6-acetyl-2-naphtholate, was readily synthesized from 6-acetyl
      2-naphthol and tert-butyldimethylchlorosilane (TBSCl). The probe exhibits high
      sensitivity and good selectivity for fluoride ions in acetonitrile. The inherent
      mechanism involves the cleavage of the Si-O bond in the probe, which induced
      yellow color formation and prominent fluorescence enhancement.

PMID- 23881574
TI  - Do birds of a feather flock together? The relationship between similarity and
      altruism in social networks.
AB  - Cooperation requires that individuals are able to identify, and preferentially
      associate with, others who have compatible preferences and the shared background
      knowledge needed to solve interpersonal coordination problems. The present study
      investigates the nature of such similarity within social networks, asking: What
      do friends have in common? And what is the relationship between similarity and
      altruism? The results show that similarity declines with frequency of contact;
      similarity in general is a significant predictor of altruism and emotional
      closeness; and, specifically, sharing a sense of humor, hobbies and interests,
      moral beliefs, and being from the same area are the best predictors. These
      results shed light on the structure of relationships within networks and provide
      a possible checklist for predicting attitudes toward strangers, and in-group
      identification. 

PMID- 23881575
TI  - Sustained zero-order release of intact ultra-stable drug-loaded liposomes from an
      implantable nanochannel delivery system.
AB  - Metronomic chemotherapy supports the idea that long-term, sustained, constant
      administration of chemotherapeutics, currently not achievable, could be effective
      against numerous cancers. Particularly appealing are liposomal formulations, used
      to solubilize hydrophobic therapeutics and minimize side effects, while extending
      drug circulation time and enabling passive targeting. As liposome alone cannot
      survive in circulation beyond 48 h, sustaining their constant plasma level for
      many days is a challenge. To address this, we develop, as a proof of concept, an
      implantable nanochannel delivery system and ultra-stable PEGylated lapatinib
      loaded liposomes, and we demonstrate the release of intact vesicles for over 18
      d. Further, we investigate intravasation kinetics of subcutaneously delivered
      liposomes and verify their biological activity post nanochannel release on BT474
      breast cancer cells. The key innovation of this work is the combination of two
      nanotechnologies to exploit the synergistic effect of liposomes, demonstrated as
      passive-targeting vectors and nanofluidics to maintain therapeutic constant
      plasma levels. In principle, this approach could maximize efficacy of metronomic
      treatments. 

PMID- 23881576
TI  - Renal denervation for arrhythmias: hope or hype?
AB  - Renal artery denervation (RDN) has been introduced as an ablation procedure that
      can effectively treat drug-resistant forms of hypertension. The ablative lesions
      reduce the afferent and efferent sympathetic nerve traffic to and from the
      kidneys, thus improving blood pressure control. Because of better control of
      blood pressure, and because the procedure reduces central sympathetic output to
      sensitive structures within the cardiovascular system, it has been hypothesized
      that RDN may be a valuable antiarrhythmic intervention. Preliminary results using
      RDN for atrial fibrillation control are promising. This review focuses on the
      mechanisms by which RDN may function as an antiarrhythmic treatment and early
      clinical results. 

PMID- 23881578
TI  - INTERMACS and MedaMACS: how will they guide future therapy?
AB  - The INTERMACS registry has played a central role in the evolving field of device
      therapy for advanced heart failure (HF). This nationwide, prospective registry of
      approved assist devices has defined the boundaries of mechanical support, tracked
      the evolution from pulsatile to continuous flow, developed new profiles for
      advanced HF, and standardized adverse event definitions. INTERMACS has guided
      current therapy and in the future will do so aided by new insights from MedaMACS,
      a parallel registry of medically-managed ambulatory patients with advanced HF.
      Together INTERMACS and MedaMACS will leverage the power of observation research
      to guide patient-centered decisions about mechanical circulatory support. 

PMID- 23881577
TI  - What's new in the treatment of acute heart failure?
AB  - Acute heart failure is associated with substantial morbidity and mortality. Goals
      of treatment are decongestion, correction of hemodynamic abnormalities, symptom
      relief, and reducing long-term morbidity and mortality. Loop diuretics are a
      first-line agent for treatment of volume overload, with ultrafiltration reserved
      for those who do not respond to pharmacologic therapy. In patients with normal or
      elevated blood pressure, vasodilators are used to correct hemodynamics and
      reverse central volume redistribution, although no currently available agent has
      been shown to improve outcomes. Intravenous inotropes and inodilators are
      associated with frequent adverse effects and are reserved for patients with
      hypotension and evidence of inadequate perfusion. Novel drugs designed to
      maximize hemodynamic benefits while minimizing adverse effects are under
      investigation, with several agents showing promise in clinical studies. 

PMID- 23881579
TI  - Computer modeling to tailor therapy for congenital heart disease.
AB  - The inherent structural and physiological complexity of congenital heart disease
      lends itself strongly to simulation. Complex hemodynamic and structural problems
      unique to congenital heart disease may be difficult to understand and the
      response to therapy or intervention uncertain. Methodologies borrowed from
      engineering, computing and mathematical sciences can be applied to such problems
      and used to inform clinical decisions. Therapy thus informed by modeling
      experiments has the potential to contribute significantly to improved clinical
      outcomes. This field remains in its infancy, and will only become used routinely
      if validation of current methods is carried out in the clinical setting. 

PMID- 23881580
TI  - Genetics of lipid traits and relationship to coronary artery disease.
AB  - Despite the critical importance of plasma lipoproteins in the development of
      atherosclerosis, varying degrees of evidence surround the causal associations of
      lipoproteins with coronary artery disease (CAD). These causal contributions can
      be assessed by employing genetic variants as unbiased proxies for lipid levels. A
      relatively large number of low-density lipoprotein cholesterol (LDL-C) variants
      strongly associate with CAD, confirming the causal impact of this lipoprotein on
      atherosclerosis. Although not as firmly established, genetic evidence supporting
      a causal role of triglycerides (TG) in CAD is growing. Conversely, high-density
      lipoprotein cholesterol (HDL-C) variants not associated with LDL-C or TG have not
      yet been shown to be convincingly associated with CAD, raising questions about
      the causality of HDL-C in atherosclerosis. Finally, genetic variants at the LPA
      locus associated with lipoprotein(a) [Lp(a)] are decisively linked to CAD,
      indicating a causal role for Lp(a). Translational investigation of CAD-associated
      lipid variants may identify novel regulatory pathways with therapeutic potential
      to alter CAD risk. 

PMID- 23881581
TI  - T-wave alternans as an arrhythmic risk stratifier: state of the art.
AB  - Microvolt level T-wave alternans (MTWA), a phenomenon of beat-to-beat variability
      in the repolarization phase of the ventricles, has been closely associated with
      an increased risk of ventricular tachyarrhythmic events (VTE) and sudden cardiac
      death (SCD) during medium- and long-term follow-up. Recent observations also
      suggest that heightened MTWA magnitude may be closely associated with short-term
      risk of impending VTE. At the subcellular and cellular level, perturbations in
      calcium transport processes likely play a primary role in the genesis of
      alternans, which then secondarily lead to alternans of action potential
      morphology and duration (APD). As such, MTWA may play a role not only in risk
      stratification but also more fundamentally in the pathogenesis of VTE. In this
      paper, we outline recent advances in understanding the pathogenesis of MTWA and
      also the utility of T-wave alternans testing for clinical risk stratification. We
      also highlight emerging clinical applications for MTWA. 

PMID- 23881583
TI  - Pregnancy in adult congenital heart disease.
AB  - Cardiac disease in pregnancy is a challenging health care problem. The number of
      cases and their complexity is increasing, such that heart disease is now the
      leading cause of maternal mortality in developed countries. Numerically, women
      with congenital heart disease (CHD) make up the majority of cases and although
      maternal mortality is infrequent, a good outcome is only achieved though
      meticulous care, which starts pre-pregnancy and continues for months after the
      pregnancy has ended. All women with CHD should be assessed and counseled before
      pregnancy and carefully monitored during pregnancy, the delivery and in the
      puerperium. In most cases, pregnancy is well tolerated but in some conditions,
      such as pulmonary hypertension or severe dilatation of the aorta, pregnancy is
      extremely high risk and should be advised against. 

PMID- 23881582
TI  - How do elevated triglycerides and low HDL-cholesterol affect inflammation and
      atherothrombosis?
AB  - This review article summarizes recent research into the mechanisms as to how
      elevated levels of triglyceride (TG) and low levels of high- density- lipoprotein
      cholesterol (HDL-C) contribute to inflammation and atherosclerosis. Evidence
      supports the role of TG-rich lipoproteins in signaling mechanisms via
      apolipoproteins C-III and free fatty acids leading to activation of NFKbeta, VCAM
      1 and other inflammatory mediators which lead to fatty streak formation and
      advanced atherosclerosis. Moreover, the cholesterol content in TG-rich
      lipoproteins has been shown to predict CAD risk better than LDL-C. In addition to
      reverse cholesterol transport, HDL has many other cardioprotective effects which
      include regulating immune function. The "functionality" of HDL appears more
      important than the level of HDL-C. Insulin resistance and central obesity
      underlie the pathophysiology of elevated TG and low HDL-C in metabolic syndrome
      and type 2 diabetes. Lifestyle recommendations including exercise and weight loss
      remain first line therapy in ameliorating insulin resistance and the adverse
      signaling processes from elevated levels of TG-rich lipoproteins and low HDL-C. 

PMID- 23881584
TI  - miR-122 promotion of the hepatitis C virus life cycle: sound in the silence.
AB  - The unusual role for miR-122 in promoting the hepatitis C virus (HCV) life cycle
      was first identified in 2005, but its mechanism of action remains
      uncharacterized. The virus appears to use the microRNA (miRNA) in a way that is
      opposed to that of normal miRNAs. Instead of interacting with sequences in the 3'
      untranslated region (UTR), miR-122 binds to two sites in the 5'-UTR, and instead
      of silencing gene expression or promoting the degradation of the viral RNA, it
      stabilizes the genome and potently augments the efficiency by which HCV RNA
      accumulates in infected cells. This review discusses the current knowledge and
      models for the mechanism by which miR-122 promotes the HCV life cycle. Annealing
      of miR-122 to the HCV genome requires particular base pairing, stimulates
      translation, and stabilizes the viral genome by blocking degradation by host
      exonucleases, but these functions are unlikely to be the whole story. We will
      discuss other possible functions for miR-122, the stages of the HCV life cycle at
      which miR-122 may influence HCV, and other related viruses that may be similarly
      regulated by miR-122. Despite our lack of detailed mechanistic information,
      antagonism of miR-122 is emerging as a powerful method to inhibit HCV infections,
      and unique to other HCV treatment strategies does not, thus far, appear to induce
      emergence of escape mutants. Used alone or in combination with other antiviral
      drugs, miR-122 antagonists could be useful to both inhibit the virus and provide
      selective pressure to inhibit the development of resistance.

PMID- 23881585
TI  - Iodine status in Korean preschool children as determined by urinary iodine
      excretion.
AB  - PURPOSE: Iodine is a trace element of thyroid hormones. Excessive or insufficient
      iodine intake is associated with various thyroid diseases. Urinary iodine (UI) is
      a sensitive indicator and a recommended barometer of population iodine intake. In
      Korea, there has been no available data regarding iodine intake in preschool
      children. We investigated the iodine intake status of Korean preschool children
      through examination of their UI. METHODS: This cross-sectional study was
      performed in 611 healthy preschool children (302 from Seoul and 309 from Masan),
      aged from 2 to 7 in 2010. UI concentration was measured by inductively coupled
      plasma-mass spectrometry. RESULTS: The median UI concentration was 438.8 MUg/L.
      Insufficient iodine intakes (<100 MUg/L) were seen in 24 children (3.9%), and
      excessive iodine ingestion (>300 MUg/L) was found in 406 children (66.4%). There
      were no significant differences in UI between different sexes and ages.
      Additionally, the median UI concentration was higher in children from Seoul
      (512.2 MUg/L) than that in children from Masan (362.4 MUg/L, P < 0.001).
      CONCLUSION: About two-thirds of Korean preschool children were in the state of
      excessive iodine intake, and 3.9% of children showed insufficient iodine intake.
      Preventive measures and follow-up for iodine intake in preschool children are
      needed.

PMID- 23881586
TI  - Prevalence of cold-related musculoskeletal pain according to self-reported
      threshold temperature among the Finnish adult population.
AB  - BACKGROUND: Exposure to cold reportedly increases musculoskeletal pains. We
      assessed the prevalence of such pain and self-reported threshold temperature (TT)
      at which the pain emerges. METHODS: A random sample of 6591 people in Finland,
      aged 25-74 years, answered a questionnaire on repeated cold-related
      musculoskeletal pain (CMP) and its TT. The response rate was 64%. We used
      quantile regression to quantify the effects of personal characteristics and
      region of residence on TT at various locations of its distribution. RESULTS: Of
      the participants, 1892 (30%) experienced CMP in at least one body site and 1692
      reported TT. Ten percent of the participants who perceived CMP did so at -2 
      degrees C, 50% at -14  degrees C and 90% at -23  degrees C. Residence in the
      South elevated TT by 1-6  degrees C compared with residence in the North,
      depending on the proportion of participants reporting CMP at various
      temperatures. Joint disorders increased TT at milder temperatures, at which only
      10% of all participants perceived CMP, whereas back disorders did so mainly at
      lower temperatures, at which 70% were affected. Overweight was associated with a
      2  degrees C lower TT, and physical inactivity with a 1  degrees C higher TT, and
      TT increased by 1  degrees C per 10-year increase in age. The greatest model
      estimated difference in median TT between subgroups was 12  degrees C.
      CONCLUSIONS: People suffering from musculoskeletal disorders and those living in
      the warmer areas of Finland need special advice to protect themselves against the
      cold. Our study provides preliminary information to support such advice.

PMID- 23881587
TI  - Self-efficacy beliefs and eating behavior in adolescent girls at-risk for excess
      weight gain and binge eating disorder.
AB  - OBJECTIVE: To examine the relationship between self-related agency beliefs and
      observed eating behavior in adolescent girls with loss of control (LOC) eating.
      METHOD: One-hundred eleven adolescent girls (14.5 +/- 1.7 years; BMI: 27.1 +/-
      2.6 kg/m(2)) were administered the General Self-Efficacy Scale and the Weight
      Efficacy Lifestyle Questionnaire (WEL). Adolescents then participated in a
      laboratory test meal. RESULTS: Greater general and eating self-efficacy were
      associated with fewer episodes of LOC eating. General self-efficacy was inversely
      related to total intake at the meal (p < .01). Only the WEL availability subscale
      score, but not the other WEL subscales, was inversely related to total energy,
      snack, and dessert intake (ps < 0.05). DISCUSSION: General self-related agency
      beliefs may be important in relation to energy consumption. Among girls
      susceptible to disordered eating and obesity, the domain-specific belief in one's
      ability to refrain from eating when food is widely available may be especially
      salient in determining overeating in the current food environment. Further
      research is therefore needed to assess the predictive validity of these beliefs
      on eating and weight outcomes.

PMID- 23881588
TI  - Solid-state UV-MALDI-MS assay of transition metal dithiocarbamate fungicides.
AB  - The determination of transition metal containing dithiocarbamate fungicides
      represents a challenging aspect of analytical object. They have a low stability,
      low solubility and stabilize versatile coordination monomers, dimers, disulfides
      and/or S-oxidized derivatives. Their diverse biological activities and
      agricultural implementation encompass plant prevention and crop protection
      against a variety of plants containing fungi and diseases of 400 pathogens and 70
      cultures. Nonetheless, those dithiocarbamates (DTCs) are banned for agricultural
      use in Europe or have expiration at years 2016-2017 because of their highly toxic
      degradation products and/or metabolites, in particular ethylene thiourea; they
      found large-scale implementations in materials research and medicine. Despite the
      broad interdisciplinary of DTC application, due to the above reasons, they have
      received little attention in the rapidly growing field of analytical chemistry,
      and in particular, the analytical mass spectrometry. Therefore, the study
      reported on qualitative, quantitative and structural analysis of ten DTCs (1-10),
      using the matrix assisted laser desorption/ionization (UV-MALDI)-Orbitrap-mass
      spectrometry (MS) contributed considerably to the implementation of the method
      for environmental and foodstuffs monitoring. Its ultrahigh resolving power and
      capacity for direct solid-state analysis, at limited number of sample
      pretreatment steps, at concentration levels of analytes of up to femtogram per
      gram resulted to achievement of a highly precise analytical information for these
      non-trivial objects. The presented fully validated method and technique is based
      on the successful ionization of DTCs embedded in three novel organic salts (M1
      M3). In this regard, the reported MS and the single-crystal X-ray diffraction
      data as well as the quantum chemical one are able to correlate the molecular
      structures in condense and in the gas phase. Despite the novelty of the
      fundamental methodological character of the research reported, the promising
      metrology contributed to the applied aspect of the UV-MALDI-MS as a robust
      analytical method for environmental and foodstuffs monitoring, which is tested on
      two commercially available crop protecting products such as Mancozeb(r) and
      Antracol(r), respectively. 

PMID- 23881589
TI  - Application of zeolites for radium removal from mine water.
AB  - For removal of radium from saline waters in Upper Silesian mines, several methods
      of purification have been developed. The most efficient one is based on
      application of barium chloride, which was implemented in full technical scale in
      two Polish coal mines several years ago. Very good results of purification have
      been achieved-the removal efficiency exceeding 95% of the initial activity.
      Another possibility for the removal of different ions from salty waters and
      brines is the application of zeolites. We found that technique as a very
      promising method for removal of not only radium isotopes from mine waters but
      also other ions (barium, iron, manganese). Treatment of several various water
      samples has been done to assess the removal efficiency for natural radionuclides.
      Preliminary results show very good effects for radium isotopes as well as for
      barium ions. In the paper, a short description of laboratory results of the
      purification of mine waters with application of synthetic zeolites is presented.

PMID- 23881590
TI  - Cd-induced phytochelatin synthesis in Dittrichia viscosa (L.) Greuter is
      determined by the dilution of the culture medium.
AB  - In this paper, we examined Cd accumulation and PC synthesis in two clones of
      Dittrichia viscosa, one with a metallicolous (DV-A) and the other with a non
      metallicolous origin (DV-W). The clones were cultured in vitro with 0 and 10 mg
      Cd L(-1) in both short-term treatments (up to 72 h) and over 10 days. We also
      examined the influence of the culture medium dilution and the PC-synthesis
      inhibitor, L-buthionine-sulfoximine (BSO), on these parameters. Similar Cd
      accumulation values were found in the two clones. No synthesis of new thiolic
      compounds was observed in Cd-treated plants cultured in vitro in Murashige and
      Skoog medium up to 72 h when compared to controls. Dilution of the culture medium
      affected PC production, increasing it in 1/2 MS and especially in 1/4 MS. Cd
      uptake did not increase in the same way, but still hyperaccumulation levels were
      exceeded in all Cd treatments. BSO addition increased the sensitivity of D.
      viscosa to Cd and diminished Cd accumulation. Nevertheless, a poor correlation
      between PCs and Cd accumulation capacity was observed since the highest Cd
      content did not correspond to the highest PC levels. All these results obtained
      suggest that PCs are important in Cd accumulation and detoxification in D.
      viscosa and also that other mechanisms might be involved in these traits. 

PMID- 23881591
TI  - Assessment of sewage sludge bioremediation at different hydraulic retention times
      using mixed fungal inoculation by liquid-state bioconversion.
AB  - Sustainable, environmental friendly, and safe disposal of sewage treatment plant
      (STP) sludge is a global expectation. Bioremediation performance was examined at
      different hydraulic retention times (HRT) in 3-10 days and organic loading rates
      (OLR) at 0.66-7.81 g chemical oxygen demand (COD) per liter per day, with mixed
      filamentous fungal (Aspergillus niger and Penicillium corylophilum) inoculation
      by liquid-state bioconversion (LSB) technique as a continuous process in large
      scale bioreactor. Encouraging results were monitored in treated sludge by LSB
      continuous process. The highest removal of total suspended solid (TSS),
      turbidity, and COD were achieved at 98, 99, and 93%, respectively, at 10 days HRT
      compared to control. The minimum volatile suspended solid/suspended solid implies
      the quality of water, which was recorded 0.59 at 10 days and 0.72 at 3 days of
      HRT. In treated supernatant with 88% protein removal at 10 days of HRT indicates
      a higher magnitude of purification of treated sludge. The specific resistance to
      filtration (SRF) quantifies the performance of dewaterability; it was recorded
      minimum 0.049 * 10(12) m kg(-1) at 10 days of HRT, which was equivalent to 97%
      decrease of SRF. The lower OLR and higher HRT directly influenced the
      bioremediation and dewaterability of STP sludge in LSB process. The obtained
      findings imply encouraging message in continuing treatment of STP sludge, i.e.,
      bioremediation of wastewater for environmental friendly disposal in near future.

PMID- 23881592
TI  - Formation of PFOA from 8:2 FTOH in closed-bottle experiments with brackish water.
AB  - The formation of perfluorooctanoate (PFOA) from 1H,1H,2H,2H-perfluorodecanol (8:2
      FTOH) was studied for the first time in laboratory experiments with brackish
      water. The water samples were collected from the Baltic Sea, which is one of the
      largest brackish water areas in the world and is polluted with PFOA and other
      perfluorinated compounds. The formation of PFOA was studied in closed-bottle
      experiments at different water temperatures. As a reference experiment, a
      modified OECD 310 test was conducted with sludge from a wastewater treatment
      plant and with brackish water. The PFOA and 8:2 FTOH were concentrated from water
      samples by solid-phase extraction (SPE) and were analysed using liquid
      chromatography-mass spectrometry. The effect of oxygen concentration on the
      formation of PFOA was studied using surface water samples with high and low
      oxygen contents. Other experiments were performed with oxygen-rich surface water
      and oxygen-deficient bottom water. The formation of PFOA was observed in all
      experiments; it was higher in the trial performed with brackish water than in the
      reference test carried out with sludge. Clear temperature dependence was observed
      in the formation of PFOA in brackish water tests; after a 30-day test period, a
      sixfold increase was observed in the amount of PFOA in surface water between the
      temperatures of 15 and 20  degrees C. Microbes were suggested as the major cause
      of the formation of PFOA, but other environmental characteristics, such as
      oxygen, could also affect the formation potential of PFOA. 

PMID- 23881593
TI  - Monitoring wild pig populations: a review of methods.
AB  - Wild pigs (Sus scrofa) are widespread across many landscapes throughout the world
      and are considered to be an invasive pest to agriculture and the environment, or
      conversely a native or desired game species and resource for hunting. Wild pig
      population monitoring is often required for a variety of management or research
      objectives, and many methods and analyses for monitoring abundance are available.
      Here, we describe monitoring methods that have proven or potential applications
      to wild pig management. We describe the advantages and disadvantages of methods
      so that potential users can efficiently consider and identify the option(s) best
      suited to their combination of objectives, circumstances, and resources. This
      paper offers guidance to wildlife managers, researchers, and stakeholders
      considering population monitoring of wild pigs and will help ensure that they can
      fulfill their monitoring objectives while optimizing their use of resources. 

PMID- 23881594
TI  - Distribution features of biological hazardous pollutants in residential
      environments in Korea.
AB  - This research has been conducted continuously since 2009 as part of a cohort of
      studies examining relationships between asthma and genetic factors, dietary
      habits, and environmental factors. Based on data from environmental research on
      house dust mites and endotoxins, which are widely known as pollutants in bedding
      that cause asthma in pregnant women and children, this work was conducted to
      obtain basic data that can be used in future cohort studies that analyze links
      between distribution of biological hazards and physical features of residential
      environments. The detection rates of house dust mite allergens, Der p1 and Der
      f1, were 52.7 and 86.5%, respectively, indicating that Der f1 is a dominant
      species in domestic indoor environments. According to comparisons between
      concentrations of house dust mites and endotoxins in bedding of pregnant women
      and children, Der p1 and endotoxins showed significantly lower concentrations in
      bedding of pregnant women compared with those in bedding of children, whereas Der
      f1 showed no significant difference in concentration according to bedding.

PMID- 23881595
TI  - Highly effective removal of 2,4-dinitrophenolic from surface water and wastewater
      samples using hydrophilic molecularly imprinted polymers.
AB  - Novel hydrophilic molecularly imprinted polymers (MIPs) with high adsorption
      capacity were used as the sorbents to remove 2,4-dinitrophenol (2,4-DNP) from
      surface water and wastewater samples. Kinetic studies, dynamic adsorption and
      selectivity experiments of hydrophilic MIPs were investigated in this study. The
      results indicated that the maximum adsorption capacity of 2,4-DNP on hydrophilic
      MIPs was 138.9 mg g(-1) and kinetic experimental data were described by the
      pseudo-second-order model. Furthermore, the effects of flow rate, initial
      concentration, pH value, and humic acid on the removal efficiency of 2,4-DNP were
      optimized. Compared with the active carbon, carbon nanotube, C18 sorbents and
      common MIPs, the removal efficiency of hydrophilic MIPs (100 mg) was very high
      with all above 92 % even though the sampling volume was more than 1 L.
      Investigated results of five times adsorption-desorption cycles indicated
      hydrophilic MIPs were high stability. In a word, the obtained results
      demonstrated that hydrophilic MIPs could be used as the effective sorbents for
      2,4-DNP removal in practical application. 

PMID- 23881597
TI  - Pristine carbon-nanotube-included supramolecular hydrogels with tunable
      viscoelastic properties.
AB  - Research investigations involving pristine carbon nanotubes (CNTs) and their
      applications in diversified fields have been gathering enormous impetus in recent
      times. One such emerging domain deals with the hybridization of CNTs within
      hydrogels to form soft nanocomposites with superior properties. However, till
      now, reports on the inclusion of pristine CNTs within low-molecular-weight
      hydrogels are very scarce due to their intrinsic feature of remaining in the
      bundled state and strong repulsive behavior to the aqueous milieu. Herein, the
      synthesis of a series of amino acid/dipeptide-based amphiphilic hydrogelators
      having a quaternary ammonium/imidazolium moiety at the polar head and a C16
      hydrocarbon chain as the hydrophobic segment is reported. The synthesized
      amphiphiles exhibited excellent hydrogelation (minimum gelation concentration
      (MGC) ~0.7-5 % w/v) as well as single-walled carbon nanotube (SWNT) dispersion
      ability in aqueous medium. Interestingly, the dispersed SWNTs were incorporated
      into the supramolecular hydrogel formed by amphiphiles with an imidazolium moiety
      at the polar end through complementary cation-pi and pi-pi interactions. More
      importantly, the newly synthesized hydrogelators were able to accommodate a
      significantly high amount of pristine SWNTs (2-3.5 % w/v) at their MGCs without
      affecting the gelating properties. This is the first time that such a huge amount
      of SWNTs has been successfully incorporated within hydrogels. The efficient
      inclusion of SWNTs to develop soft nanocomposites was thoroughly investigated by
      spectroscopic and microscopic methods. Remarkably, the developed nanocomposites
      showed manifold enhancement (~85-fold) in their mechanical strength compared with
      native hydrogel without SWNTs. The viscoelastic properties of these
      nanocomposites were readily tuned by varying the amount of incorporated CNTs. 

PMID- 23881596
TI  - A mechanistic framework for in vitro-in vivo extrapolation of liver membrane
      transporters: prediction of drug-drug interaction between rosuvastatin and
      cyclosporine.
AB  - BACKGROUND AND OBJECTIVES: The interplay between liver metabolising enzymes and
      transporters is a complex process involving system-related parameters such as
      liver blood perfusion as well as drug attributes including protein and lipid
      binding, ionisation, relative magnitude of passive and active permeation.
      Metabolism- and/or transporter-mediated drug-drug interactions (mDDIs and tDDIs)
      add to the complexity of this interplay. Thus, gaining meaningful insight into
      the impact of each element on the disposition of a drug and accurately predicting
      drug-drug interactions becomes very challenging. To address this, an in vitro-in
      vivo extrapolation (IVIVE)-linked mechanistic physiologically based
      pharmacokinetic (PBPK) framework for modelling liver transporters and their
      interplay with liver metabolising enzymes has been developed and implemented
      within the Simcyp Simulator((r)). METHODS: In this article an IVIVE technique for
      liver transporters is described and a full-body PBPK model is developed. Passive
      and active (saturable) transport at both liver sinusoidal and canalicular
      membranes are accounted for and the impact of binding and ionisation processes is
      considered. The model also accommodates tDDIs involving inhibition of multiple
      transporters. Integrating prior in vitro information on the metabolism and
      transporter kinetics of rosuvastatin (organic-anion transporting polypeptides
      OATP1B1, OAT1B3 and OATP2B1, sodium-dependent taurocholate co-transporting
      polypeptide [NTCP] and breast cancer resistance protein [BCRP]) with one clinical
      dataset, the PBPK model was used to simulate the drug disposition of rosuvastatin
      for 11 reported studies that had not been used for development of the
      rosuvastatin model. RESULTS: The simulated area under the plasma concentration
      time curve (AUC), maximum concentration (C max) and the time to reach C max (t
      max) values of rosuvastatin over the dose range of 10-80 mg, were within 2-fold
      of the observed data. Subsequently, the validated model was used to investigate
      the impact of coadministration of cyclosporine (ciclosporin), an inhibitor of
      OATPs, BCRP and NTCP, on the exposure of rosuvastatin in healthy volunteers.
      CONCLUSION: The results show the utility of the model to integrate a wide range
      of in vitro and in vivo data and simulate the outcome of clinical studies, with
      implications for their design.

PMID- 23881598
TI  - Access to beta-keto esters by palladium-catalyzed carbonylative coupling of aryl
      halides with monoester potassium malonates.

PMID- 23881599
TI  - A novel method for culturing human glottic cells.
AB  - OBJECTIVES/HYPOTHESIS: The objective of this basic investigation was to describe
      a new method of preparing primary monolayer cultures of human glottic cells. To
      our knowledge, this is the first report of the culturing of healthy human glottic
      cells. This technique may be of use for other applications in the challenging
      field of laryngeal diseases. STUDY DESIGN: Individual prospective cohort study.
      METHODS: Tissue samples were collected from 15 patients who underwent laryngeal
      surgery due to chronic laryngitis or larynx carcinoma. An inverted phase
      microscope was used to study the cultured cells, and immunocytochemistry using a
      mouse anti-human cytokeratin 19 monoclonal antibody was performed to identify
      epithelial cells. The relationship between the culture results and several
      patient variables was evaluated. RESULTS: Cultures were positive in 40% of
      samples. The total and supracricoid laryngectomy groups had the highest rate of
      culture positivity (P < .02). CONCLUSIONS: The current study provides
      methodological details that will allow other research groups to replicate this
      model of glottic cell culture.

PMID- 23881600
TI  - Differences of SiHa (human cancer of cervix) and BMG-1 (brain glioma) cell lines
      as 2D and 3D cultures.
AB  - Cell cultures have seen much progress in the numbers available cell lines, their
      applications and culture techniques. Three dimensional cultures and co-cultures
      are examples of strategies that bring in vitro conditions closer to natural in
      vivo systems. We describe here, the formation of cell aggregates in three
      dimensional conditions for the cell lines SiHa and BMG-1 utilizing agarose
      hydrogels. The optimal conditions for best aggregate formation were identified
      and the culture phases for the cell lines as monolayers and as aggregates were
      compared. Differences in protein profiles, susceptibility to a genotoxic drug and
      the antigenic properties of the protein extracts of the two cell lines, as can be
      induced by their aggregate formation were studied. The results from the four
      approaches indicate the usefulness of culturing cells as aggregates. Such systems
      using simple material and methods offer us an efficient way of utilizing cell
      lines for a variety of applications.

PMID- 23881601
TI  - Modeling the absorbed dose to the common carotid arteries following radioiodine
      treatment of benign thyroid disease.
AB  - INTRODUCTION: External fractionated radiotherapy of cancer increases the risk of
      cardio- and cerebrovascular events, but less attention has been paid to the
      potential side effects on the arteries following internal radiotherapy with
      radioactive iodine (RAI), i.e. 131-iodine. About 279 per million citizens in the
      western countries are treated each year with RAI for benign thyroid disorders
      (about 140,000 a year in the EU), stressing that it is of clinical importance to
      be aware of even rare radiation-induced side effects. In order to induce or
      accelerate atherosclerosis, the dose to the carotid arteries has to exceed 2 Gy
      which is the known lower limit of ionizing radiation to affect the endothelial
      cells and thereby to induce atherosclerosis. OBJECTIVE: To estimate the radiation
      dose to the carotid arteries following RAI therapy of benign thyroid disorders.
      METHODS: Assuming that the lobes of the thyroid gland are ellipsoid, that the
      carotid artery runs through a part of the lobes, that there is a homogeneous
      distribution of RAI in the lobes, and that the 24 h RAI uptake in the thyroid is
      35 % of the (131)I orally administrated, we used integrated modules for bioassay
      analysis and Monte Carlo simulations to calculate the dose in Gy/GBq of
      administrated RAI. RESULTS: The average radiation dose along the arteries is 4-55
      Gy/GBq of the (131)I orally administrated with a maximum dose of approximately 25
      85 Gy/GBq. The maximum absorbed dose rate to the artery is 4.2 Gy/day per GBq
      (131)I orally administrated. CONCLUSION: The calculated radiation dose to the
      carotid arteries after RAI therapy of benign thyroid disorder clearly exceeds the
      2 Gy known to affect the endothelial cells and properly induce atherosclerosis.
      This simulation indicates a relation between the deposited dose in the arteries
      following RAI treatment and an increased risk of atherosclerosis and subsequent
      cerebrovascular events such as stroke.

PMID- 23881602
TI  - Rosiglitazone promotes the differentiation of Langerhans cells and inhibits that
      of other dendritic cell types from CD133 positive hematopoietic precursors.
AB  - Dendritic cells and their precursors express PPAR-gamma, whose stimulation has
      inhibitory effects on the maturation and function of dendritic cells in vivo.
      Dendritic cells can differentiate in vitro from CD133+ progenitors; the influence
      of PPAR-gamma stimulation on this process is unknown. We have addressed the
      effect of PPAR-gamma agonist rosiglitazone, at a concentration as used in
      clinics, on the differentiation of dendritic cells from human CD133+ progenitors.
      Cells were harvested from cord blood by density gradient and immunomagnetic
      separation, and cultured for 18 days with fetal calf serum, cytokines and 1
      MUmol/L rosiglitazone. Analyses included flow cytometry, electron microscopy and
      mixed lymphocyte reaction. As expected, control cells generated without
      rosiglitazone were dendritic, expressed MHC-II, CD80, CD83 and CD86 and
      stimulated mixed reaction potently. A minority of cells expressed the Langerhans
      cell marker CD207/langerin, but none contained Birbeck granules. With
      rosiglitazone much fewer cells were generated; they were all dendritic, expressed
      differentiation and maturation-related antigens in higher percentage and were
      better stimulators of lymphocytes than those generated without the drug. The vast
      majority of cells expressed CD207/langerin and many contained Birbeck granules,
      i.e. were full-fledged Langerhans cells. We conclude that stimulation of PPAR
      gamma, while negatively affecting the number of generated cells, promotes the
      maturation of human cord blood CD133 positive precursors into efficient,
      immunostimulating dendritic cells with a Langerhans cell phenotype.

PMID- 23881603
TI  - Lives that introns lead after splicing.
AB  - After transcription of a eukaryotic pre-mRNA, its introns are removed by the
      spliceosome, joining exons for translation. The intron products of splicing have
      long been considered 'junk' and destined only for destruction. But because they
      are large in size and under weak selection constraints, many introns have been
      evolutionarily repurposed to serve roles after splicing. Some spliced introns are
      precursors for further processing of other encoded RNAs such as small nucleolar
      RNAs, microRNAs, and long noncoding RNAs. Other intron products have long half
      lives and can be exported to the cytoplasm, suggesting that they have roles in
      translation. Some viruses encode introns that accumulate after splicing and play
      important but mysterious roles in viral latency. Turnover of most lariat-introns
      is initiated by cleavage of their internal 2'-5' phosphodiester bonds by a unique
      debranching endonuclease, and the linear products are further degraded by
      exoribonucleases. However, several introns appear to evade this turnover pathway
      and the determinants of their stability are largely unknown. Whereas many stable
      intron products were discovered serendipitously, new experimental and
      computational tools will enable their direct identification and study. Finally,
      the origins and mechanisms of mobility of eukaryotic introns are mysterious, and
      mechanistic studies of the intron life cycle may yield new insights into how they
      arose and became widespread.

PMID- 23881604
TI  - Severely elevated transaminases in an adolescent male with anorexia nervosa.
AB  - Anorexia nervosa (AN) is a serious disorder that is associated with numerous
      medical complications and affects both females and males. Severely elevated
      transaminases have been reported in adult and younger females. We report the
      first case of elevated transaminases in an adolescent male with AN. The
      pathophysiologic mechanism of severely elevated serum transaminases observed in
      malnourished adolescent males with AN is complex and appears to be
      multifactorial. We present the first case of an adolescent male with AN who
      developed severely elevated serum transaminases that normalized with improved
      nutrition and weight gain. Liver injury in patients with AN is a complex medical
      complication that appears to be multifactorial in origin. In this case,
      starvation-induced autophagy in the human liver was considered one of the most
      likely mechanisms to explain hepatocytic injury in this patient.

PMID- 23881605
TI  - Targeted opioid receptor antagonists in the treatment of alcohol use disorders.
AB  - In 1994, the US Food and Drug Administration approved the MU-opioid receptor
      antagonist naltrexone to treat alcohol dependence. However, treatments requiring
      daily administration, such as naltrexone, are inconsistently adhered to in
      substance abusing populations, and constant medication exposure can increase risk
      of adverse outcomes, e.g., hepatotoxicity. This has fostered a 'targeted' or 'as
      needed' approach to opioid receptor antagonist treatment, in which medications
      are used only in anticipation of or during high-risk situations, including times
      of intense cravings. Initial studies of the ability of targeted naltrexone to
      reduce drinking-related outcomes were conducted in problem drinkers and have been
      extended into larger, multi-site, placebo-controlled investigations with positive
      results. Another MU-opioid receptor antagonist, nalmefene, has been studied on an
      'as-needed' basis to reduce heavy drinking in alcohol-dependent individuals.
      These studies include three large multi-site trials in Europe of up to 1 year in
      duration, and serve as the basis for the recent approval of nalmefene by the
      European Medicines Agency as an 'as-needed' adjunctive treatment for alcohol
      dependence. We review potential moderators of opioid receptor antagonist
      treatment response including subjective assessments, objective clinical measures
      and genetic variants. In sum, the targeted or 'as-needed' approach to treatment
      with opioid antagonists is an efficacious harm-reduction strategy for problem
      drinking and alcohol dependence. 

PMID- 23881606
TI  - Impact of moderate calorie restriction on testicular morphology and endocrine
      function in adult rhesus macaques (Macaca mulatta).
AB  - We previously reported that moderate calorie restriction (CR) has minimal impact
      on testicular gene expression in young adult rhesus macaques, and no obvious
      negative impact on semen quality or plasma testosterone levels. We now extend
      these findings by examining the influence of CR on various aspects of the
      reproductive axis of older males, including 24-h circulating testosterone levels,
      testicular gene expression, and testicular morphology. Young adult and old adult
      male rhesus macaques were subjected to either 30 % CR for 5-7 years, or were fed
      a standard control diet. Analysis of the 24-h plasma testosterone profiles
      revealed a significant age-associated decline, but no evidence for CR-induced
      suppression in either the young or old males. Similarly, expression profiling of
      key genes associated with testosterone biosynthesis and Leydig cell maintenance
      showed no significant CR-induced changes in either the young or old animals. The
      only evidence for CR-associated negative effects on the testis was detected in
      the old animals at the histological level; when old CR animals were compared with
      their age-matched controls, there was a modest decrease in seminiferous tubule
      diameter and epithelium height, with a concomitant increase in the number of
      depleted germ cell lines. Reassuringly, data from this study and our previous
      study suggest that moderate CR does not negatively impact 24-h plasma
      testosterone profiles or testicular gene expression. Although there appear to be
      some minor CR-induced effects on testicular morphology in old animals, it is
      unclear if these would significantly compromise fertility. 

PMID- 23881607
TI  - Elevated cysteine-rich protein 61 (CCN1) promotes skin aging via upregulation of
      IL-1beta in chronically sun-exposed human skin.
AB  - Chronic exposure of human skin to solar ultraviolet (UV) irradiation causes
      premature skin aging, which is characterized by reduced type I collagen
      production and increased fragmentation of the dermal collagenous extracellular
      matrix. This imbalance of collagen homeostasis is mediated, in part, by elevated
      expression of the matricellular protein cysteine-rich protein 61 (CCN1), in
      dermal fibroblasts, the primary collagen producing cell type in human skin. Here,
      we report that the actions of CCN1 are mediated by induction of interleukin 1beta
      (IL-1beta). CCN1 and IL-1beta are strikingly induced by acute UV irradiation, and
      constitutively elevated in sun-exposed prematurely aged human skin. Elevated CCN1
      rapidly induces IL-1beta, inhibits type I collagen production, and upregulates
      matrix metalloproteinase-1, which degrades collagen fibrils. Blockade of IL-1beta
      actions by IL-1 receptor antagonist largely prevents the deleterious effects of
      CCN1 on collagen homeostasis. Furthermore, knockdown of CCN1 significantly
      reduces induction of IL-1beta by UV irradiation, and thereby partially prevents
      collagen loss. These data demonstrate that elevated CCN1promotes inflammaging and
      collagen loss via induction of IL-1beta and thereby contributes to the
      pathophysiology of premature aging in chronically sun-exposed human skin. 

PMID- 23881608
TI  - Short-term strength training improves muscle quality and functional capacity of
      elderly women.
AB  - To assess effects of a short-term strength training (ST) program on muscle
      quality (MQ) and functional capacity, 36 sedentary elderly women (age = 66.0 +/-
      8 year, height = 159.1 +/- 9.2 cm, body mass = 68.3 +/- 12.1 kg, body fat = 37.0
      +/- 4.2 %) were randomly divided into an experimental group (EG; n = 19) or a
      control group (CG; n = 17). The EG performed two to three sets of 12-15 repeats
      of leg press, knee extension, and knee flexion exercises, 2 days/week for 6
      weeks. Before and after training, lower body one repetition maximum (1RM),
      functional performance tests, quadriceps femoris muscle thickness (MT), and
      muscle quality (MQ) (1RM and quadriceps MT quotient) were assessed. After
      training, only the EG showed significant improvements in 1RM (p < 0.05), 30-s sit
      to-stand (p < 0.001), and 8 foot up-and-go (p < 0.001). In addition, only in the
      EG, significant increases in all quadriceps femoris MT measurements (vastus
      lateralis, vastus medialis, vastus intermedius, and rectus femoris) (p <= 0.05),
      and MQ (p < 0.001) were demonstrated. No changes were observed in the CG.
      Furthermore, there were significant associations between individual changes in MQ
      and corresponding changes in 30-s sit-to-stand (r = 0.62, p < 0.001), and 8 foot
      up-and-go (r = -0.71, p < 0.001). In conclusion, a ST program of only 6 weeks was
      sufficient to enhance MQ of the knee extensors in elderly women, which resulted
      in beneficial changes in functional capacity.

PMID- 23881609
TI  - Impact of a drug utilization review program on high-risk use of prescription
      controlled substances.
AB  - BACKGROUND: Prescription drug abuse has prompted considerable concern. We
      evaluated a retrospective drug utilization review program to reduce controlled
      substance use among individuals with high-risk utilization. METHODS: We analyzed
      pharmacy claims from a large pharmaceutical benefits manager. For each eligible
      member, we calculated a controlled substance score based on the number and type
      of claims, prescribers and pharmacies, and utilization patterns over three
      months. Two state health plans sent controlled substance letters to prescribers
      of members meeting or exceeding a plan- and pre-specified controlled substance
      score. Two different state health plans did not send such letters. We used a
      difference-in-difference design and generalized estimating equations to quantify
      the impact of the program on the mean difference in reduction of the controlled
      substance score over six months. RESULTS: Eligible members in the intervention
      and comparison states had similar baseline mean controlled substance scores (19.0
      vs. 18.6, p = 0.36). Adjusting for individuals' age, sex and pharmacy risk group
      score, reductions in the mean controlled substance score were greater in the
      intervention than comparison cohort (5.67 vs. 4.31, p = 0.01), corresponding with
      a 34.0% reduction in the intervention cohort compared to a 25.5% reduction in the
      comparison cohort. Changes were driven primarily by reductions in the number of
      controlled substance claims filled (30.5% vs. 23.1%, p = 0.01), as well as by a
      non-statistically significant trend towards reductions in the number of
      prescribers and pharmacies used (26.9% vs. 20.1%, p = 0.07). CONCLUSIONS:
      Retrospective drug utilization review programs may reduce controlled substance
      scores and claims among individuals with patterns suggesting high-risk
      utilization.

PMID- 23881610
TI  - Hip arthroscopy for extra-articular hip disease.
AB  - The increasing popularity and success of hip arthroscopy has led to the
      development of related techniques for treating hip pathologies external to the
      joint proper. These minimally invasive endoscopic procedures serve in a
      diagnostic role to complement clinical evaluations and offer a therapeutic
      alternative to traditional open techniques. The indications for extra-articular
      hip endoscopy continue to expand. Recent literature describes applications for
      treating greater trochanteric pain syndrome, internal snapping hip, deep gluteal
      syndrome, and subspine impingement and for diagnosing and treating extra
      articular sources of hip pain in patients who have undergone hip arthroplasty. 

PMID- 23881611
TI  - Synthesis and biological evaluation of N-substituted sophocarpinic acid
      derivatives as coxsackievirus B3 inhibitors.
AB  - A series of novel N-substituted sophocarpinic acid derivatives was designed,
      synthesized, and evaluated for their anti-enteroviral activities against
      coxsackievirus type B3 (CVB3) and coxsackievirus type B6 (CVB6) in Vero cells.
      Structure-activity relationship analysis revealed that the introduction of a
      benzenesulfonyl moiety on the 12-nitrogen atom in (E)-beta,gamma-sophocarpinic
      acid might significantly enhance anti-CVB3 activity. Among the derivatives, (E)
      12-N-(m-cyanobenzenesulfonyl)-beta,gamma-sophocarpinic acid (11 m), possessing a
      meta-cyanobenzenesulfonyl group, exhibited potent activity against CVB3 with a
      selectivity index (SI) of 107. Furthermore, compound 11 m also showed a good oral
      pharmacokinetic profile, with an AUC value of 7.29 MUM h-1 in rats, and good
      safety through the oral route in mice, with an LD50 value of >1000 mg kg-1; these
      values suggest a druggable characteristic. Therefore, compound 11 m was selected
      for further investigation as a promising CVB3 inhibitor. We consider (E)
      beta,gamma-N-(benzenesulfonyl)sophocarpinic acids to be a novel class of anti
      CVB3 agents.

PMID- 23881612
TI  - RECK inhibits stemness gene expression and tumorigenicity of gastric cancer cells
      by suppressing ADAM-mediated Notch1 activation.
AB  - The Reversion-inducing Cysteine-rich Protein with Kazal Motifs (RECK) gene
      encodes a membrane-anchored glycoprotein that exhibits strong inhibitory activity
      against various matrix metalloproteinases (MMPs) and a disintegrin and
      metalloproteinase 10 (ADAM10). RECK functions as a tumor suppressor by inhibiting
      migration, invasion, and angiogenesis. However, whether RECK can modulate the
      stem-like phenotypes of cancer cells is not known. In this study, we demonstrate
      that RECK is down-regulated in gastric cancer cells and is further reduced in
      CD133-positive cancer stem-like cells. Ectopic expression of RECK induces down
      regulation of the expression of stemness genes including Sox2, Oct4, and Nanog
      and the cancer stem cell marker CD133. Treatment of DAPT (a gamma-secretase
      inhibitor) or TAPI-2 (a hydroxamate-based inhibitor of MMPs, tumor necrosis
      factor alpha converting enzyme and ADAM17) reduces Notch1 shedding and activation
      which results in attenuation of stemness genes and CD133. Our data show that
      ADAM10 and ADAM17 are co-pulled down by RECK suggesting a physical interaction
      between RECK and ADAMs on cell surface. In addition, RECK suppresses sphere
      formation and sphere size of CD133-positive gastric cancer cells. Overexpression
      of Notch intracellular domain (NICD) or ADAM17 effectively reverse the inhibitory
      effect of RECK in CD133-positive cells. More importantly, RECK reduces
      tumorigenic activity of CD133-positive cells in vivo. Conversely, knockdown of
      RECK in non-tumorigenic GI2 cells increases stemness and CD133 expression and
      sphere forming ability. Collectively, these results indicate that RECK represses
      stemness gene expression and stem-like properties by inhibiting ADAM-mediated
      Notch1 shedding and activation.

PMID- 23881613
TI  - [Cognitive reserve and linguistic skills in healthy elderly persons].
AB  - INTRODUCTION: One research strategy that can be used with the cognitive reserve
      is to establish groups of elderly persons who differ in key variables that affect
      the cognitive reserve and then compare their performance in cognitive tests.
      AIMS: To determine which of the variables that have an influence on the cognitive
      reserve (measured by means of the cognitive reserve questionnaire) are related
      with performance in the Boston Naming Test, and in the vocabulary and grammar
      comprehension tests from the ECCO_Senior battery. SUBJECTS AND METHODS: The
      sample consisted of 83 elderly persons aged between 60 and 75 years. RESULTS AND
      CONCLUSIONS: Schooling, parents' schooling, job and reading habits are closely
      related to the performance of the elderly in naming, grammar comprehension and
      vocabulary. Schooling affects the comprehension of sentences with a higher
      propositional density, and reading habits seem to be closely related with the
      comprehension of sentences that are more complex in terms of their syntax.
      Schooling and job affect the performance obtained when dealing with verbs in the
      vocabulary test.

PMID- 23881614
TI  - [Audiovisual stimulation in children with severely limited motor function: does
      it improve their quality of life?].
AB  - INTRODUCTION: Children with neurological diseases that impose severe limitations
      on their mobility have a deficient quality of life (QL). AIMS: To study whether
      the QL of such patients improves with the application of a programme of
      audiovisual stimulation. PATIENTS AND METHODS: A prospective study was conducted
      on nine children, six of whom were males (mean age: 42.6 +/- 28.6 months), with
      severely limited mobility and who had been hospitalised for long periods. Two
      audiovisual stimulation programmes were produced and applied, together with
      videos, by means of a specially designed structure. The stimulus was applied
      twice a day for 10 minutes over 20 days. The first ten days the stimulus was
      carried out in a passive manner and the second block of ten days it was performed
      with the guidance of the observer. Biological, behavioural and cognitive
      variables were recorded and an adapted QL survey was applied. RESULTS: Three
      cases of spinal muscular atrophy, two of congenital muscular dystrophy, two of
      myopathy and two with other conditions were diagnosed. Eight patients completed
      the follow-up. From the baseline point of view, they presented a regular QL (7.2
      +/- 1.7 points; median: 7.0; range: 6-10), which improved to good on finishing
      the therapy (9.4 +/- 1.2 points; median: 9.0; range: 8-11), with an intra
      individual difference of 2.1 +/- 1.6 (median: 2.5; range: -1 to 4; CI 95% = 0.83
      3.42; p = 0.006). Improved cognition and a favourable perception in the
      caregivers were detected. No changes took place in the biological or behavioural
      variables. CONCLUSIONS: Audiovisual stimulation can be used to enhance the
      quality of life of children with severely limited mobility.

PMID- 23881615
TI  - [Posterior reversible encephalopathy in a case of late-onset eclampsia].
AB  - INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical
      radiological syndrome with acute or sub-acute presenting symptoms characterised
      by the presence of headache, vomiting, epileptic seizures, visual disorders and
      altered level of consciousness associated to lesions mainly located in the white
      matter of the posterior regions of the brain. CASE REPORT: A 32-year-old female
      who developed PRES in the postpartum period secondary to late-onset eclampsia.
      Ten days after giving birth, the patient presented a clinical picture consisting
      in headache, epileptic seizures, blindness and deterioration of the level of
      consciousness. The magnetic resonance imaging scan confirmed the predominant
      involvement of posterior white matter. CONCLUSIONS: Although eclampsia is a
      typical condition in pregnancy and the immediate postpartum period, it must be
      remembered that there is also a late-onset form that may occur after the birth
      and might be the cause of other syndromes such as PRES. Although the prognosis in
      these cases is usually favourable, treatment must be established as early as
      possible, with rapid control of the blood pressure and seizures in order to avoid
      permanent brain damage. This syndrome must always be taken into account in women
      with epileptic seizures or other neurological symptoms during the postpartum
      period.

PMID- 23881616
TI  - [Antidepressants in epilepsy].
AB  - Depression is a common condition in patients with epilepsy that entails a
      deterioration of the quality of life of this population and that, therefore,
      requires appropriate treatment. The potential risk of antidepressants in relation
      to the seizure threshold is overestimated by many professionals, and this has an
      influence when it comes to making the decision to treat them. It sometimes means
      that the patients do not receive antidepressant drugs. In this regard, the aim of
      this review is to present the current state of the art in terms of the safety of
      antidepressants in patients with epilepsy. A search of the medical literature was
      conducted and, following its analysis, the most significant results are
      presented. Current information indicates that most antidepressants are safe for
      epileptic patients at therapeutic doses and that the risk of seizures occurs
      mainly in cases of overdose. Preferred drugs for treating depression in epilepsy
      are serotonin reuptake inhibitors. Bupropion and tricyclic antidepressants must
      be avoided. 

PMID- 23881617
TI  - [Tics and Tourette syndrome in literature, cinema and television].
AB  - INTRODUCTION: Different neurological diseases have often been portrayed in
      literature, cinema and television. Tics and Tourette syndrome, for example, are
      commonly represented from different perspectives, which are sometimes very
      realistic but in some cases are used for more dramatic purposes or to make a
      character look ridiculous. One of the main effects of these inadequate views is
      to further stigmatise those who suffer these movement disorders. AIMS: To review
      the way tics and Tourette syndrome have been portrayed in certain literary works,
      films and television. DEVELOPMENT: Tics are rapid, stereotypic, involuntary,
      recurring, non-purposeful movements of the skeletal and pharyngeal-laryngeal
      muscles. In Gilles de la Tourette syndrome a number of tics are associated to
      involuntary vocalisations (echolalia, coprolalia). They begin in childhood and
      are usually associated to obsessive-compulsive behaviours. These disorders have
      appeared in literature in works such as Little Dorrit, Angel Guerra, La torre de
      los siete jorobados or Motherless Brooklyn. Film-makers have also shown an
      interest in tics and Tourette syndrome and they have been portrayed in films such
      as Young and Innocent, The Tic Code or Matchstick Men. Likewise, a number of
      television series also contain characters with these disorders, including
      Shameless, Ally McBeal, Quincy, M.E. or L.A. Law. CONCLUSIONS: Tics and Tourette
      syndrome have frequently been portrayed in literature, cinema and television,
      sometimes in a very realistic manner. In other cases, however, the way they are
      dealt with has only helped to create false beliefs and stereotyped images of the
      disorders.

PMID- 23881618
TI  - [Hyperdense carotid T in stroke: 'tree sign'].

PMID- 23881620
TI  - [Favourable response to the use of intravenous immunoglobulins in central pontine
      myelinolysis].

PMID- 23881621
TI  - Imaging brain functional and metabolic changes in restless legs syndrome.
AB  - Even though the pathophysiology of restless legs syndrome is not completely
      understood, several imaging studies have contributed to our understanding of the
      disease. Functional and metabolic impairment seems to be the pathophysiological
      core, tied to a single brain network or multiple connected brain networks, via
      neurotransmitter modifications. Positron emission tomography and single photon
      emission computed tomography studies support a dysfunction of dopaminergic
      pathways, involving not only the nigrostriatal pathway but also the mesolimbic
      pathway. Furthermore, a possible role of serotonergic neurotransmission has been
      suggested. Functional magnetic resonance imaging studies have demonstrated in
      restless legs syndrome patients a pathologic activation of cerebral areas
      belonging to both the sensorimotor and the limbic networks. Proton magnetic
      resonance spectroscopy has confirmed abnormality of the limbic system and
      suggested the presence of a glutamatergic disorder. Finally magnetic resonance
      studies using iron-sensitive sequences have demonstrated reduced iron content in
      several regions of the brain of restless legs syndrome patients. In this review
      we attempt to integrate all current imaging study results into a convergent
      pathophysiological interpretation. 

PMID- 23881622
TI  - Parkinson disease and sleep: sleep-wake changes in the premotor stage of
      Parkinson disease; impaired olfaction and other prodromal features.
AB  - Parkinson disease (PD) has a premotor stage where neurodegeneration occurs before
      parkinsonism becomes apparent. Identification of individuals at this stage
      provides an opportunity to study early disease progression and test disease
      modifying interventions. Hyposmia, constipation, depression and hypersomnia are
      part of this premotor phase and predictive of future development of PD. However,
      these features are common in the general population, and they are most often the
      result of causes other than incipient PD. In contrast, most individuals with
      idiopathic REM sleep behavior disorder (IRBD) eventually develop PD and other
      synucleinopathies. IRBD individuals with hyposmia, substantia nigra
      hyperechogenicity, and abnormal striatal dopamine transporter imaging findings
      have increased short-term risk of developing a synucleinopathy. IRBD is an
      optimal target to test disease-modifying agents in the PD prodromal phase. Serial
      dopamine transporter imaging, but not olfactory tests, may serve to monitor the
      disease process in future disease-modifying trials in IRBD. 

PMID- 23881623
TI  - Functional MRI and outcome in traumatic coma.
AB  - Advances in task-based functional MRI (fMRI), resting-state fMRI (rs-fMRI), and
      arterial spin labeling (ASL) perfusion MRI have occurred at a rapid pace in
      recent years. These techniques for measuring brain function have great potential
      to improve the accuracy of prognostication for civilian and military patients
      with traumatic coma. In addition, fMRI, rs-fMRI, and ASL perfusion MRI have
      provided novel insights into the pathophysiology of traumatic disorders of
      consciousness, as well as the mechanisms of recovery from coma. However,
      functional neuroimaging techniques have yet to achieve widespread clinical use as
      prognostic tests for patients with traumatic coma. Rather, a broad spectrum of
      methodological hurdles currently limits the feasibility of clinical
      implementation. In this review, we discuss the basic principles of fMRI, rs-fMRI,
      and ASL perfusion MRI and their potential applications as prognostic tools for
      patients with traumatic coma. We also discuss future strategies for overcoming
      the current barriers to clinical implementation. 

PMID- 23881625
TI  - Phosphoramidate tantalum complexes for room-temperature C-H functionalization:
      hydroaminoalkylation catalysis.

PMID- 23881624
TI  - Opportunistic infections of the central nervous system in the transplant patient.
AB  - Therapeutic advances in transplantation medicine have resulted in ever expanding
      patient populations that receive organ or stem cell transplantation. Modern
      potent immunomodulatory therapies have resulted in improvements in allograft and
      patient survival, but, consequently, as a result of the immunosuppressive state,
      transplant recipients are highly vulnerable to infection, including those that
      affect the central nervous system (CNS). CNS infections present a diagnostic and
      therapeutic challenge for clinicians involved in the care of the transplant
      patient, with a propensity to result in profound morbidity and often high
      mortality in this patient population. Here, we review major opportunistic
      pathogens of the CNS seen in transplant patients, highlighting distinguishing
      epidemiologic and clinical features. 

PMID- 23881639
TI  - Examining duration of binge eating episodes in binge eating disorder.
AB  - OBJECTIVE: The primary goal of this article is to examine and clarify
      characteristics of binge eating in individuals with binge eating disorder (BED),
      particularly the duration of binge eating episodes, as well as potential
      differences between individuals with shorter compared to longer binge eating
      episodes. METHOD: Two studies exploring binge eating characteristics in BED were
      conducted. Study 1 examined differences in clinical variables among individuals
      (N = 139) with BED who reported a short (<2 h) versus long (>= 2 h) average binge
      duration. Study 2 utilized an ecological momentary assessment design to examine
      the duration and temporal pattern of binge eating episodes in the natural
      environment in a separate sample of nine women with BED. RESULTS: Participants in
      Study 1 who were classified as having long duration binge eating episodes
      displayed greater symptoms of depression and lower self-esteem, but did not
      differ on other measures of eating disorder symptoms, compared to those with
      short duration binge eating episodes. In Study 2, the average binge episode
      duration was approximately 42 min, and binge eating episodes were most common
      during the early afternoon and evening hours, as well as more common on weekdays
      versus weekends. DISCUSSION: Past research on binge episode characteristics,
      particularly duration, has been limited to studies of binge eating episodes in
      bulimia nervosa. This study contributes to the existing literature on
      characteristics of binge eating in BED.

PMID- 23881640
TI  - Effect of eurycomanone on cytochrome P450 isoforms CYP1A2, CYP2A6, CYP2C8,
      CYP2C9, CYP2C19, CYP2E1 and CYP3A4 in vitro.
AB  - Eurycomanone, an active constituent isolated from Eurycoma longifolia Jack, was
      examined for modulatory effects on cytochrome P450 (CYP) isoforms CYP1A2, CYP2A6,
      CYP2C8, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 using in vitro assays. The IC50 value
      was determined to assess the potencies of modulation for each CYP isoform. Our
      results indicated that eurycomanone did not potently inhibit any of the CYP
      isoforms investigated, with IC50 values greater than 250 MUg/ml. Hence there
      appears to be little likelihood of drug-herb interaction between eurycomanone or
      herbal products with high content of this compound and CYP drug substrates via
      CYP inhibition.

PMID- 23881641
TI  - Single-particle spectroscopy on large SAPO-34 crystals at work: methanol-to
      olefin versus ethanol-to-olefin processes.
AB  - The formation of hydrocarbon pool (HCP) species during methanol-to-olefin (MTO)
      and ethanol-to-olefin (ETO) processes have been studied on individual micron
      sized SAPO-34 crystals with a combination of in situ UV/Vis, confocal
      fluorescence, and synchrotron-based IR microspectroscopic techniques. With in
      situ UV/Vis microspectroscopy, the intensity changes of the lambda=400 nm
      absorption band, ascribed to polyalkylated benzene (PAB) carbocations, have been
      monitored and fitted with a first-order kinetics at low reaction temperatures.
      The calculated activation energy (Ea ) for MTO, approximately 98 kJ mol(-1) ,
      shows a strong correlation with the theoretical values for the methylation of
      aromatics. This provides evidence that methylation reactions are the rate
      determining steps for the formation of PAB. In contrast for ETO, the Ea value is
      approximately 60 kJ mol(-1) , which is comparable to the Ea values for the
      condensation of light olefins into aromatics. Confocal fluorescence microscopy
      demonstrates that during MTO the formation of the initial HCP species are
      concentrated in the outer rim of the SAPO-34 crystal when the reaction
      temperature is at 600 K or lower, whereas larger HCP species are gradually formed
      inwards the crystal at higher temperatures. In the case of ETO, the observed egg
      white distribution of HCP at 509 K suggests that the ETO process is kinetically
      controlled, whereas the square-shaped HCP distribution at 650 K is indicative of
      a diffusion-controlled process. Finally, synchrotron-based IR microspectroscopy
      revealed a higher degree of alkylation for aromatics for MTO as compared to ETO,
      whereas high reaction temperatures favor dealkylation processes for both the MTO
      and ETO processes. 

PMID- 23881642
TI  - BKCa and hEag1 channels regulate cell proliferation and differentiation in human
      bone marrow-derived mesenchymal stem cells.
AB  - Human bone marrow-derived mesenchymal stem cells (MSCs) serve as a reservoir for
      the continuous renewal of various mesenchymal tissues; however, cellular
      physiology of ion channels is not fully understood. The present study
      investigated potential roles of large-conductance Ca(2+) -activated potassium
      (BKCa ) channels and ether-a-go-go potassium (hEag1 or Kv10.1) channels in
      regulating cell proliferation and differentiation in human MSCs. We found that
      inhibition of BKCa with paxilline or hEag1 with astemizole, or knockdown of BKCa
      with shRNAs targeting KCa1.1 or hEag1 channels with shRNAs targeting KCNH1
      arrested the cells at G0/G1 phase. In addition, silencing BKCa or hEag1 channels
      significantly reduced adipogenic differentiation with decrease of lipid
      accumulation and expression of the adipocyte marker PPARgamma, and decreased
      osteogenic differentiation with reduction of mineral precipitation and
      osteocalcin. These effects were accompanied with a reduced cyclin D1, cyclin E, p
      ERK1/2, and p-Akt. Our results demonstrate that BKCa and hEag1 channels not only
      regulate cell proliferation, but also participate in the adipogenic and
      osteogenic differentiations in human MSCs, which indicates that BKCa and hEag1
      channels may be essential in maintaining bone marrow physiological function and
      bone regeneration.

PMID- 23881643
TI  - Ambulatory pediatric oncology CLABSIs: epidemiology and risk factors.
AB  - BACKGROUND: To compare the burden of central line-associated bloodstream
      infections (CLABSIs) in ambulatory versus inpatient pediatric oncology patients,
      and identify the epidemiology of and risk factors associated with ambulatory
      CLABSIs. PROCEDURE: We prospectively identified infections and retrospectively
      identified central line days and characteristics associated with CLABSIs from
      January 2009 to October 2010. A nested case-control design was used to identify
      characteristics associated with ambulatory CLABSIs. RESULTS: We identified 319
      patients with central lines. There were 55 ambulatory CLABSIs during 84,705
      ambulatory central line days (0.65 CLABSIs per 1,000 central line days (95% CI
      0.49, 0.85)), and 19 inpatient CLABSIs during 8,682 inpatient central line days
      (2.2 CLABSIs per 1,000 central lines days (95% CI 1.3, 3.4)). In patients with
      ambulatory CLABSIs, 13% were admitted to an intensive care unit and 44% had their
      central lines removed due to the CLABSI. A secondary analysis with a sub-cohort,
      suggested children with tunneled, externalized catheters had a greater risk of
      ambulatory CLABSI than those with totally implantable devices (IRR 20.6, P <
      0.001). Other characteristics independently associated with ambulatory CLABSIs
      included bone marrow transplantation within 100 days (OR 16, 95% CI 1.1, 264),
      previous bacteremia in any central line (OR 10, 95% CI 2.5, 43) and less than 1
      month from central line insertion (OR 4.2, 95% CI 1.0, 17). CONCLUSIONS: In
      pediatric oncology patients, three times more CLABSIs occur in the ambulatory
      than inpatient setting. Ambulatory CLABSIs carry appreciable morbidity and have
      identifiable, associated factors that should be addressed in future ambulatory
      CLABSI prevention efforts.

PMID- 23881644
TI  - Use of tyrosine kinase inhibitors in a patient with Brugada syndrome and chronic
      myeloid leukemia.
AB  - The treatment and prognosis of chronic myeloid leukemia have dramatically changed
      since the introduction of tyrosine kinase inhibitors, but although several
      clinical trials have examined their safety with respect to heart function, no
      data are yet available about the use of these drugs in patients with Brugada
      syndrome. We report a case of Brugada syndrome diagnosed during tyrosine kinase
      inhibitor therapy in a 69-year-old Caucasian male with meningioma and chronic
      myeloid leukemia. This case report highlights the importance of an integrated
      approach among hematologists and cardiologists to ensure appropriate treatment
      with tyrosine kinase inhibitors in patients affected by chronic myeloid leukemia
      who also suffer from Brugada syndrome. 

PMID- 23881645
TI  - Expression of myeloid antigens on lymphoblast surface in childhood acute
      lymphoblastic leukemia at diagnosis and its effect on early response to
      treatment: a preliminary report.
AB  - Immunodiagnosis of acute lymphoblastic leukemia (ALL) is based on the assessment
      of surface antigens. There are also cases in which both lymphoid and myeloid
      antigens can be found on the surface of lymphoblasts. The purpose of our research
      was to assess the expression of myeloid and lymphoblastic antigens in children
      with ALL, and to determine the impact of surface antigens on early response to
      treatment. 58 children [33 girls (56.9 %), 25 boys (43.2 %)] with ALL were
      studied. Response to treatment was assessed on days 8, 15, and 33. Univariate
      logistic regression analysis of the effect of myeloid antigens (MyAg) on response
      to treatment on days 8 and 33 revealed expression of any MyAg on lymphoblast
      surface as a factor associated with poor response to treatment. The multivariate
      logistic regression analysis of treatment response on day 33, showed that the
      expression of CD13 antigen on lymphoblast surface is a key factor affecting
      delayed remission (p = 0.03; odds ratio 0.12; 95 % CI 0.01-0.81). The expression
      of MyAg in childhood ALL adversely affects early response to treatment. The
      expression of CD13 antigen on day 33 is a key factor affecting complete remission
      in ALL patients. 

PMID- 23881646
TI  - Asymmetric autocatalysis induced by cinnabar: observation of the enantioselective
      adsorption of a 5-pyrimidyl alkanol on the crystal surface.

PMID- 23881647
TI  - Vitamin D and skeletal growth and development.
AB  - Vitamin D is critical to bone mineral metabolism and to the growth and
      development of the skeleton. Optimizing vitamin D status could be one of the
      cornerstones to optimize skeletal growth and achieving the maximum peak bone mass
      soon after the completion of adolescence. Maximizing peak bone mass is considered
      to be the key to primary prevention of osteoporosis. There is controversy,
      however, about what constitutes a healthy vitamin D status based on the most
      abundant circulating metabolite of vitamin D, namely 25 hydroxyvitamin D (25 OHD)
      in plasma or serum; and even the value of 25 OHD that should be used to define
      vitamin D deficiency. We reviewed the recent data on circulating 25 OHD
      concentrations and its relationship with skeletal growth in apparently healthy
      children and in those with nutritional vitamin D deficiency. 

PMID- 23881648
TI  - The cell's nucleolus: an emerging target for chemotherapeutic intervention.
AB  - The transient nucleolus plays a central role in the up-regulated synthesis of
      ribosomal RNA (rRNA) to sustain ribosome biogenesis, a hallmark of aberrant cell
      growth. This function, in conjunction with its unique pathohistological features
      in malignant cells and its ability to mediate apoptosis, renders this sub-nuclear
      structure a potential target for chemotherapeutic agents. In this Minireview,
      structurally and functionally diverse small molecules are discussed that have
      been reported to either interact with the nucleolus directly or perturb its
      function indirectly by acting on its dynamic components. These molecules include
      all major classes of nucleic-acid-targeted agents, antimetabolites, kinase
      inhibitors, anti-inflammatory drugs, natural product antibiotics, oligopeptides,
      as well as nanoparticles. Together, these molecules are invaluable probes of
      structure and function of the nucleolus. They also provide a unique opportunity
      to develop novel strategies for more selective and therefore better-tolerated
      chemotherapeutic intervention. In this regard, inhibition of RNA polymerase-I
      mediated rRNA synthesis appears to be a promising mechanism for killing cancer
      cells. The recent development of molecules targeted at G-quadruplex-forming rRNA
      gene sequences, which are currently undergoing clinical trials, seems to attest
      to the success of this approach. 

PMID- 23881649
TI  - Enemas during labour.
AB  - BACKGROUND: Although the use of enemas during labour usually reflects the
      preference of the attending healthcare provider, enemas may cause discomfort for
      women. OBJECTIVES: To assess the effects of enemas applied during the first stage
      of labour on maternal and neonatal outcomes. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013), the
      Cochrane Central Register of Controlled Trials and Database of Abstracts of
      Reviews of Effectiveness (The Cochrane Library 2013, Issue 5), PubMed (1966 to 31
      May 2013), LILACS (31 May 2013), the Search Portal of the International Clinical
      Trials Registry Platform (ICTRP) (31 May 2013), Health Technology Assessment
      Program, UK (31 May 2013), Medical Research Council, UK (31 May 2013), The
      Wellcome Trust, UK (31 May 2013) and reference lists of retrieved articles.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) in which an enema was
      administered during the first stage of labour and which included assessment of
      possible neonatal or puerperal morbidity or mortality. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed studies for inclusion. MAIN
      RESULTS: Four RCTs (1917 women) met the inclusion criteria. One study was judged
      as having a low risk of bias. In the meta-analysis we conducted of two trials, we
      found no significant difference in infection rates for puerperal women (two RCTs;
      594 women; risk ratio (RR) 0.66, 95% confidence (CI) 0.42 to 1.04). No
      significant differences were found in neonatal umbilical infection rates (two
      RCTs; 592 women; RR 3.16, 95% CI 0.50 to 19.82; I(2) 0%. In addition, meta
      analysis of two studies found that there were no significant differences in the
      degree of perineal tear between groups. Finally, meta-analysis of two trials
      found no significant differences in the mean duration of labour. AUTHORS'
      CONCLUSIONS: The evidence provided by the four included RCTs shows that enemas do
      not have a significant beneficial effect on infection rates such as perineal
      wound infection or other neonatal infections and women's satisfaction. These
      findings speak against the routine use of enemas during labour, therefore, such
      practice should be discouraged.

PMID- 23881650
TI  - Homocysteine lowering interventions for peripheral arterial disease and bypass
      grafts.
AB  - BACKGROUND: Elevated plasma levels of the amino acid homocysteine
      (hyperhomocysteinaemia) are associated with narrowing or blocking of the arteries
      (atherosclerosis). Treatment to lower homocysteine levels has been shown to be
      both effective and cheap in healthy volunteers. However, the impact of reducing
      homocysteine levels on the progression of atherosclerosis and patency of the
      vessels after treatment for atherosclerosis is still unknown and forms the basis
      for this review. This is the second update of a review first published in 2002.
      OBJECTIVES: To assess the effects of plasma homocysteine lowering therapy on the
      clinical progression of disease in people with peripheral arterial disease (PAD)
      and hyperhomocysteinaemia including, as a subset, those who have undergone
      surgical or radiological intervention. SEARCH METHODS: For this update, the
      Cochrane Peripheral Vascular Disease Group Trials Search Co-ordinator (TSC)
      searched the Specialised Register (last searched January 2013) and CENTRAL (2012,
      Issue 12). Trial databases were searched by the TSC (January 2013) for details of
      ongoing and unpublished studies. We also searched the reference lists of relevant
      articles. SELECTION CRITERIA: Randomised trials in which participants with PAD
      and hyperhomocysteinaemia were allocated to either homocysteine lowering therapy
      or no treatment, including participants before and after surgical or radiological
      interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed trial quality and extracted the data. Information on adverse events was
      collected from the trials. MAIN RESULTS: Two randomised trials with a total of
      161 participants were included in this review. The studies did not report on
      mortality and rate of limb loss. One randomised trial with a total of 133
      participants showed that there was a significant improvement in ankle brachial
      index (ABI) in participants who received folic acid compared with placebo (mean
      difference (MD) 0.07, 95% confidence interval (CI) 0.04 to 0.11, P < 0.001) and
      in participants who received 5-methyltetrahydrofolate (5-MTHF) versus placebo (MD
      0.05, 95% CI 0.01 to 0.10, P = 0.009). A second trial with a total of 18
      participants showed that there was no difference (P non-significant) in ABI in
      participants who received a multivitamin B supplement (mean +/- SEM: 0.7 +/- 01)
      compared with placebo (mean +/- SEM: 0.8 +/- 0.1). No major events were reported.
      AUTHORS' CONCLUSIONS: Currently, no recommendation can be made regarding the
      value of treatment of hyperhomocysteinaemia in peripheral arterial disease.
      Further, well constructed trials are urgently required.

PMID- 23881651
TI  - Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric
      tonsillectomy.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain
      relief following tonsillectomy in children. However, as they inhibit platelet
      aggregation and prolong bleeding time they could cause increased perioperative
      bleeding. The overall risk remains unclear. This review was originally published
      in 2005 and was updated in 2010 and in 2012. OBJECTIVES: The primary objective of
      this review was to assess the effects of NSAIDs on bleeding with paediatric
      tonsillectomy. Our secondary outcome was to establish whether NSAIDs affect the
      incidence of other postoperative complications when compared to other forms of
      analgesia. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 10); MEDLINE
      (inception until October 2012); EMBASE (inception until October 2012); Current
      Problems (produced by the UK Medicines Control Agency), MedWatch (produced by the
      US Food and Drug Administration) and the Australian Adverse Drug Reactions
      Bulletins (to May 2010). The original search was performed in August 2004. We
      also contacted manufacturers and researchers in the field. SELECTION CRITERIA: We
      included randomized controlled trials assessing NSAIDs in children, up to and
      including 16 years of age, undergoing elective tonsillectomy or
      adenotonsillectomy. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted the data. We contacted study authors for
      additional information, where necessary. MAIN RESULTS: We included 15 studies
      that involved 1101 children in this updated review. One study was added as a
      result of our 2012 search, another previously included study was removed due to
      lack of randomization. Fourteen included studies compared NSAIDs with other
      analgesics or placebo and reported on bleeding requiring surgical intervention.
      The use of NSAIDs was associated with a non-significant increase in the risk of
      bleeding requiring surgical intervention: Peto odds ratio (OR) 1.69 (95%
      confidence interval (CI) 0.71 to 4.01). Ten studies involving 365 children
      reported perioperative bleeding requiring non-surgical intervention. NSAIDs did
      not significantly alter the number of perioperative bleeding events requiring non
      surgical intervention: Peto OR 0.99 (95% CI 0.41 to 2.40) but the confidence
      intervals did not exclude an increased risk. Thirteen studies involving 1021
      children reported postoperative vomiting. There was less vomiting when NSAIDs
      were used as part of the analgesic regime than when NSAIDs were not used: Mantel
      Haenszel (M-H) risk ratio (RR) 0.72 (95% CI 0.61 to 0.85). AUTHORS' CONCLUSIONS:
      There is insufficient evidence to exclude an increased risk of bleeding when
      NSAIDs are used in paediatric tonsillectomy. They do however confer the benefit
      of a reduction in vomiting.

PMID- 23881652
TI  - Simple behavioural interventions for nocturnal enuresis in children.
AB  - BACKGROUND: Nocturnal enuresis (bedwetting) is a socially disruptive and
      stressful condition which affects around 15% to 20% of five year olds and up to
      2% of adults. Although there is a high rate of spontaneous remission, the social,
      emotional and psychological costs can be great. Behavioural interventions for
      treating bedwetting are defined as interventions that require a behaviour or
      action by the child which promotes night dryness and includes strategies which
      reward that behaviour. Behavioural interventions are further divided into:(a)
      simple behavioural interventions - behaviours or actions that can be achieved by
      the child without great effort; and(b) complex behavioural interventions -
      multiple behavioural interventions which require greater effort by the child and
      parents to achieve, including enuresis alarm therapy.This review focuses on
      simple behavioural interventions.Simple behavioural interventions are often used
      as a first attempt to improve nocturnal enuresis and include reward systems such
      as star charts given for dry nights, lifting or waking the children at night to
      urinate, retention control training to enlarge bladder capacity (bladder
      training) and fluid restriction. Other treatments such as medications,
      complementary and miscellaneous interventions such as acupuncture, complex
      behavioural interventions and enuresis alarm therapy are considered elsewhere.
      OBJECTIVES: To determine the effects of simple behavioural interventions in
      children with nocturnal enuresis.The following comparisons were made:1. simple
      behavioural interventions versus no active treatment;2. any single type of simple
      behavioural intervention versus another behavioural method (another simple
      behavioural intervention, enuresis alarm therapy or complex behavioural
      interventions);3. simple behavioural interventions versus drug treatment alone
      (including placebo drugs) or drug treatment in combination with other
      interventions. SEARCH METHODS: We searched the Cochrane Incontinence Group
      Specialised Trials Register, which contains trials identified from the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, and
      handsearching of journals and conference proceedings (searched 15 December 2011).
      The reference lists of relevant articles were also searched. SELECTION CRITERIA:
      All randomised or quasi-randomised trials of simple behavioural interventions for
      treating nocturnal enuresis in children up to the age of 16. Studies which
      included children with daytime urinary incontinence or children with organic
      conditions were also included in this review if the focus of the study was on
      nocturnal enuresis. Trials focused solely on daytime wetting and trials of adults
      with nocturnal enuresis were excluded. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed the quality of the eligible trials and extracted
      data. Differences between reviewers were settled by discussion with a third
      reviewer. MAIN RESULTS: Sixteen trials met the inclusion criteria, involving 1643
      children of whom 865 received a simple behavioural intervention. Within each
      comparison, outcomes were mostly addressed by single trials, precluding meta
      analysis. The only exception was bladder training versus enuresis alarm therapy
      which included two studies and demonstrated that alarm therapy was superior to
      bladder training.In single small trials, rewards, lifting and waking and bladder
      training were each associated with significantly fewer wet nights, higher full
      response rates and lower relapse rates compared to controls. Simple behavioural
      interventions appeared to be less effective when compared with other known
      effective interventions (such as enuresis alarm therapy and drug therapies with
      imipramine and amitriptyline). However, the effect was not sustained at follow-up
      after completion of treatment for the drug therapies. Based on one small trial,
      cognitive therapy also appeared to be more effective than rewards. When one
      simple behavioural therapy was compared with another, there did not appear to be
      one therapy that was more effective than another. AUTHORS' CONCLUSIONS: Simple
      behavioural methods may be superior to no active treatment but appear to be
      inferior to enuresis alarm therapy and some drug therapy (such as imipramine and
      amitriptyline). Simple behavioural therapies could be tried as first line
      treatment before considering enuresis alarm therapy or drug therapy, which may be
      more demanding and have adverse effects, although evidence supporting their
      efficacy is lacking.

PMID- 23881653
TI  - Partial liquid ventilation for preventing death and morbidity in adults with
      acute lung injury and acute respiratory distress syndrome.
AB  - BACKGROUND: Acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) are syndromes of severe respiratory failure that are associated with
      substantial mortality and morbidity. Artifical ventilatory support is commonly
      required and may exacerbate lung injury. Partial liquid ventilation (PLV) has
      been proposed as a less injurious form of ventilatory support for these patients.
      Although PLV has been shown to improve gas exchange and to reduce inflammation in
      experimental models of ALI, a previous systematic review did not find any
      evidence to support or refute its use in humans with ALI and ARDS. OBJECTIVES:
      The primary objective of this review was to assess whether PLV reduced mortality
      (at 28 d, at discharge from the intensive care unit (ICU), at discharge from
      hospital and at one, two and five years) in adults with ALI or ARDS when compared
      with conventional ventilatory support.Secondary objectives were to determine how
      PLV compared with conventional ventilation with regard to duration of invasive
      mechanical ventilation, duration of respiratory support, duration of oxygen
      therapy, length of ICU stay, length of hospital stay, incidence of infection,
      long-term cognitive impairment, long-term health related quality of life, long-
      term lung function, long-term morbidity costs and adverse events. The following
      adverse events were considered: hypoxia (arterial PO2 <80 mm Hg), pneumothorax
      (any air leak into the pleural space requiring therapeutic intervention),
      hypotension (systolic blood pressure < 90 mm Hg sustained for longer than two
      minutes or requiring treatment with fluids or vasoactive drugs), bradycardia
      (heart rate < 50 beats per minute sustained for longer than one minute or
      requiring therapeutic intervention) and cardiac arrest (absence of effective
      cardiac output). SEARCH METHODS: In this updated review, we searched the Cochrane
      Central Register of Controlled Trials (CENTRAL Issue 10, 2012, in The Cochrane
      Library; MEDLINE (Ovid SP, 1966 to November 2012); EMBASE (Ovid SP, 1980 to
      November 2012) and CINAHL (EBSCOhost,1982 to November 2012) for published
      studies. In our original review, we searched until May 2004.Grey literature was
      identified by searching conference proceedings and trial registries and by
      contacting experts in the field. SELECTION CRITERIA: As in the original review,
      review authors selected randomized controlled trials that compared PLV with other
      forms of ventilation in adults (16 y of age or older) with ALI or ARDS, reporting
      one or more of the following: mortality; duration of mechanical ventilation,
      respiratory support, oxygen therapy, stay in the intensive care unit or stay in
      hospital; infection; long-term cognitive impairment or health-related quality of
      life; long-term lung function or cost. DATA COLLECTION AND ANALYSIS: Two review
      authors independently evaluated the quality of the relevant studies and extracted
      the data from included studies. MAIN RESULTS: In this updated review, one new
      eligible study was identified and included, yielding a total of two eligible
      studies (including a combined total of 401 participants). Of those 401
      participants, 170 received 'high'-dose partial liquid ventilation (i.e. a mean
      dose of at least 20 mL/kg), 99 received 'low-dose' partial liquid ventilation
      (i.e. a dose of 10 mL/kg) and 132 received conventional mechanical ventilation
      (CMV). Pooled estimates of effect were calculated for all those who received
      'high'-dose PLV versus conventional ventilation. No evidence indicated that
      'high'-dose PLV either reduced mortality at 28 d (risk ratio (RR) 1.21, 95%
      confidence interval (CI) 0.79 to 1.85, P = 0.37) or increased the number of days
      free of CMV at 28 d (mean difference (MD) -2.24, 95% CI -4.71 to 0.23, P = 0.08).
      The pooled estimate of effect for bradycardia in those who received PLV was
      significantly greater than in those who received CMV (RR 2.51, 95% CI 1.31 to
      4.81, P = 0.005). Pooled estimates of effect for the following adverse events-
      hypoxia, pneumothorax, hypotension and cardiac arrest- all showed a
      nonsignificant trend towards a higher occurrence of these events in those treated
      with PLV. Because neither eligible study addressed morbidity or mortality beyond
      28 d, it was not possible to determine the effect of PLV on these outcomes.
      AUTHORS' CONCLUSIONS: No evidence supports the use of PLV in ALI or ARDS; some
      evidence suggests an increased risk of adverse events associated with its use.

PMID- 23881654
TI  - Oral morphine for cancer pain.
AB  - BACKGROUND: This is the second updated version of a Cochrane review first
      published in Issue 4, 2003 of The Cochrane Library and first updated in 2007.
      Morphine has been used for many years to relieve pain. Oral morphine in either
      immediate release or modified release form remains the analgesic of choice for
      moderate or severe cancer pain. OBJECTIVES: To determine the efficacy of oral
      morphine in relieving cancer pain, and assess the incidence and severity of
      adverse effects. SEARCH METHODS: We searched the following databases: Cochrane
      Pain, Palliative and Supportive Care Group Trials Register (June 2013); Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue
      5, May); MEDLINE (1966 to June 2013); and EMBASE (1974 to June 2013). SELECTION
      CRITERIA: Published randomised controlled trials (RCTs) using placebo or active
      comparators reporting on the analgesic effect of oral morphine in adults and
      children with cancer pain. Trials with fewer than ten participants were excluded.
      DATA COLLECTION AND ANALYSIS: One review author extracted data, which were
      checked by another review author. There were insufficient comparable data for
      meta-analysis to be undertaken or to produce numbers needed to treat (NNTs) for
      the analgesic effect. We extracted any available data on the number or proportion
      of participants with 'no worse than mild pain' or treatment success (very
      satisfied, or very good or excellent on patient global impression scales). MAIN
      RESULTS: Ten new studies (638 participants) were identified for this update,
      bringing the total of included studies to 62, with 4241 participants. Thirty-six
      studies used a cross-over design ranging from one to 15 days, with the greatest
      number (11) for seven days for each arm of the trial.Fifteen studies compared
      oral morphine modified release (Mm/r) preparations with morphine immediate
      release (MIR). Fourteen studies compared Mm/r in different strengths; six of
      these included 24-hour modified release products. Fifteen studies compared Mm/r
      with other opioids. Six studies compared MIR with other opioids. Two studies
      compared oral Mm/r with rectal Mm/r. Three studies compared MIR with MIR by a
      different route of administration. Two studies compared Mm/r with Mm/r at
      different times and two compared MIR with MIR given at a different time. One
      study was found comparing each of the following: Mm/r tablet with Mm/r
      suspension; Mm/r with non-opioids; MIR with non-opioids; and oral morphine with
      epidural morphine.In this update a standard of 'no worse than mild pain' was set
      equivalent to a score of 30/100 mm or less on a visual analogue pain intensity
      scale (VAS), or the equivalent in other pain scales. Eighteen studies achieved
      this level of pain relief on average, and no study reported that good levels of
      pain relief were not attained. Where results were reported for individual
      participants in 17 studies, 'no worse than mild pain' was achieved by 96% of
      participants (362/377), and an outcome equivalent to treatment success in 63%
      (400/638).Morphine is an effective analgesic for cancer pain. Pain relief did not
      differ between Mm/r and MIR. Modified release versions of morphine were effective
      for 12- or 24-hour dosing depending on the formulation. Daily doses in studies
      ranged from 25 mg to 2000 mg with an average of between 100 mg and 250 mg. Dose
      titration was undertaken with both instant release and modified release products.
      A small number of participants did not achieve adequate analgesia with morphine.
      Adverse effects were common and approximately 6% of participants discontinued
      treatment because of intolerable adverse effects. AUTHORS' CONCLUSIONS: The
      effectiveness of oral morphine has stood the test of time, but the randomised
      trial literature for morphine is small given the importance of this medicine.
      Most trials recruited fewer than 100 participants and did not provide appropriate
      data for meta-analysis. Only a few reported how many people had good pain relief,
      but where it was reported, over 90% had no worse than mild pain within a
      reasonably short time period. The review demonstrates the wide dose range of
      morphine used in studies, and that a small percentage of participants are unable
      to tolerate oral morphine. The review also shows the wide range of study designs,
      and inconsistency in cross-over designs. Trial design was frequently based on
      titration of morphine or comparator to achieve adequate analgesia, then crossing
      participants over in cross-over design studies. It was not clear if these trials
      are sufficiently powered to detect any clinical differences between formulations
      or comparator drugs. New studies added to the review reinforce the view that it
      is possible to use modified release morphine to titrate to analgesic effect.
      There is qualitative evidence that oral morphine has much the same efficacy as
      other available opioids.

PMID- 23881655
TI  - Influenza vaccination for healthcare workers who care for people aged 60 or older
      living in long-term care institutions.
AB  - BACKGROUND: Healthcare workers' influenza rates are unknown but may be similar to
      those of the general public. Healthcare workers may transmit influenza to
      patients. OBJECTIVES: To identify all randomised controlled trials (RCTs) and non
      RCTs assessing the effects of vaccinating healthcare workers on the incidence of
      laboratory-proven influenza, pneumonia, death from pneumonia and admission to
      hospital for respiratory illness in those aged 60 years or older resident in long
      term care institutions (LTCIs). SEARCH METHODS: We searched CENTRAL 2013, Issue
      2, MEDLINE (1966 to March week 3, 2013), EMBASE (1974 to March 2013), Biological
      Abstracts (1969 to March 2013), Science Citation Index-Expanded (1974 to March
      2013) and Web of Science (2006 to March 2013). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) and non-RCTs of influenza vaccination of healthcare
      workers caring for individuals aged 60 years or older in LTCIs and the incidence
      of laboratory-proven influenza and its complications (lower respiratory tract
      infection, or hospitalisation or death due to lower respiratory tract infection)
      in individuals aged 60 years or older in LTCIs. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted data and assessed risk of bias. MAIN RESULTS: We
      identified four cluster-RCTs (C-RCTs) (n = 7558) and one cohort study (n =
      12,742) of influenza vaccination for HCWs caring for individuals >= 60 years in
      LTCFs. Three RCTs (5896 participants) provided outcome data that met our
      criteria. These three studies were comparable in study populations, intervention
      and outcome measures. The studies did not report adverse events. The principal
      sources of bias in the studies related to attrition and blinding. The pooled risk
      difference (RD) from the three cluster-RCTs for laboratory-proven influenza was 0
      (95% confidence interval (CI) -0.03 to 0.03) and for hospitalisation was RD 0
      (95% CI -0.02 to 0.02). The estimated risk of death due to lower respiratory
      tract infection was also imprecise (RD -0.02, 95% CI -0.06 to 0.02) in
      individuals aged 60 years or older in LTCIs. Adjusted analyses which took into
      account the cluster design did not differ substantively from the pooled analysis
      with unadjusted data. AUTHORS' CONCLUSIONS: The results for specific outcomes:
      laboratory-proven influenza or its complications (lower respiratory tract
      infection, or hospitalisation or death due to lower respiratory tract illness)
      did not identify a benefit of healthcare worker vaccination on these key
      outcomes. This review did not find information on co-interventions with
      healthcare worker vaccination: hand-washing, face masks, early detection of
      laboratory-proven influenza, quarantine, avoiding admissions, antivirals and
      asking healthcare workers with influenza or influenza-like-illness (ILI) not to
      work. This review does not provide reasonable evidence to support the vaccination
      of healthcare workers to prevent influenza in those aged 60 years or older
      resident in LTCIs. High-quality RCTs are required to avoid the risks of bias in
      methodology and conduct identified by this review and to test further these
      interventions in combination.

PMID- 23881656
TI  - Diet or exercise, or both, for weight reduction in women after childbirth.
AB  - BACKGROUND: Weight retention after pregnancy may contribute to obesity. It is
      known that diet and exercise are recommended components of any weight loss
      programme in the general population. However, strategies to achieve healthy body
      weight among postpartum women have not been adequately evaluated. OBJECTIVES: The
      objectives of this review were to evaluate the effect of diet, exercise or both
      for weight reduction in women after childbirth, and to assess the impact of these
      interventions on maternal body composition, cardiorespiratory fitness,
      breastfeeding performance and other child and maternal outcomes. SEARCH METHODS:
      We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31
      January 2012) and LILACS (31 January 2012). We scanned secondary references and
      contacted experts in the field. We updated the search of the Cochrane Pregnancy
      and Childbirth Group's Trials Register on 30 April 2013 and added the results to
      the awaiting classification section of the review. SELECTION CRITERIA: All
      published and unpublished randomised controlled trials (RCTs) and quasi
      randomised trials of diet or exercise or both, among women during the postpartum
      period. DATA COLLECTION AND ANALYSIS: Both review authors independently assessed
      trial quality and extracted data. Results are presented using risk ratio (RR) for
      categorical data and mean difference (MD) for continuous data. Data were analysed
      with a fixed-effect model. A random-effects model was used in the presence of
      heterogeneity. MAIN RESULTS: Fourteen trials were included, but only 12 trials
      involving 910 women contributed data to outcome analysis. Women who exercised did
      not lose significantly more weight than women in the usual care group (two
      trials; n = 53; MD -0.10 kg; 95% confidence interval (CI) -1.90 to 1.71). Women
      who took part in a diet (one trial; n = 45; MD -1.70 kg; 95% CI -2.08 to -1.32),
      or diet plus exercise programme (seven trials; n = 573; MD -1.93 kg; 95% CI -2.96
      to -0.89; random-effects, T2 = 1.09, I2 = 71%), lost significantly more weight
      than women in the usual care group. There was no difference in the magnitude of
      weight loss between diet alone and diet plus exercise group (one trial; n = 43;
      MD 0.30 kg; 95% CI -0.06 to 0.66). The interventions seemed not to affect
      breastfeeding performance adversely. AUTHORS' CONCLUSIONS: Evidence from this
      review suggests that both diet and exercise together and diet alone help women to
      lose weight after childbirth. Nevertheless, it may be preferable to lose weight
      through a combination of diet and exercise as this improves maternal
      cardiorespiratory fitness and preserves fat-free mass, while diet alone reduces
      fat-free mass. This needs confirmation in large trials of high methodological
      quality. For women who are breastfeeding, more evidence is required to confirm
      whether diet or exercise, or both, is not detrimental for either mother or baby.

PMID- 23881657
TI  - Intermittent drug techniques for schizophrenia.
AB  - BACKGROUND: Antipsychotic medication is considered the mainstay of treatment for
      schizophrenia and is generally regarded as highly effective, especially in
      controlling positive symptoms. However, long-term antipsychotic exposure has been
      associated with a range of adverse effects, including extra-pyramidal symptoms
      (EPS), neuroleptic malignant syndrome (NMS), tardive dyskinesia and death.
      Intermittent drug techniques refers to the 'use of medication only during periods
      of incipient relapse or symptom exacerbation rather than continuously'. The aim
      is to reduce the risk of typical adverse effects of antipsychotics by 'reducing
      long-term medication exposure for patients who are receiving maintenance
      treatment while limiting the risk of relapse', with a further goal of improving
      social functioning resulting from the reduction of antipsychotic-induced side
      effects OBJECTIVES: To review the effects of different intermittent drug
      techniques compared with maintenance treatment in people with schizophrenia or
      related disorders. SEARCH METHODS: We searched The Cochrane Schizophrenia Group
      Trials Register (April 2012) and supplemented this by contacting relevant study
      authors, handsearching relevant intermittent drug treatment articles and manually
      searching reference lists. SELECTION CRITERIA: All randomised controlled trials
      (RCTs) that compared intermittent drug techniques with standard maintenance
      therapy for people with schizophrenia. Primary outcomes of interest were relapse
      and hospitalisation. DATA COLLECTION AND ANALYSIS: At least two review authors
      selected trials, assessed quality and extracted data. We calculated risk ratios
      (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data and
      estimated the 95% confidence interval (CI) around this. For non-skewed continuous
      endpoint data extracted from valid scales, we estimated mean difference (MD)
      between groups with a 95% CI. Where data displayed heterogeneity, these were
      analysed using a random-effects model. Skewed data are presented in tables. We
      assessed overall quality for clinically important outcomes using the GRADE
      approach. MAIN RESULTS: Of 241 records retrieved by the search, 17 trials
      conducted between 1961 and 2011, involving 2252 participants with follow-up from
      six weeks to two years, were included. Homogenous data demonstrated that
      instances of relapse were significantly higher in people receiving any
      intermittent drug treatment in the long term (n = 436, 7 RCTs, RR 2.46, 95% CI
      1.70 to 3.54, moderate quality evidence). Intermittent treatment was shown to be
      more effective than placebo, however, and demonstrated that significantly less
      people receiving intermittent antipsychotics experienced full relapse by medium
      term (n = 290, 2 RCTs, RR 0.37, 95% CI 0.24 to 0.58, very low quality evidence).
      Hospitalisation rates were higher for people receiving any intermittent drug
      treatment by long term (n = 626, 5 RCTs, RR 1.65, 95% CI 1.33 to 2.06, moderate
      quality evidence). Results demonstrated little difference in instances of tardive
      dyskinesia in groups with any intermittent drug technique versus maintenance
      therapy, with equivocal results (displaying slight heterogeneity) at long term (n
      = 165, 4 RCTs, RR 1.15, 95% CI 0.58 to 2.30, low quality evidence). AUTHORS'
      CONCLUSIONS: Results of this review support the existing evidence that
      intermittent antipsychotic treatment is not as effective as continuous,
      maintained antipsychotic therapy in preventing relapse in people with
      schizophrenia. More research is needed to assess any potential benefits or harm
      of intermittent treatment regarding adverse effects typically associated with
      maintained antipsychotic treatment, as well as any cost-effectiveness of this
      experimental treatment.

PMID- 23881658
TI  - First-line allogeneic hematopoietic stem cell transplantation of HLA-matched
      sibling donors compared with first-line ciclosporin and/or antithymocyte or
      antilymphocyte globulin for acquired severe aplastic anemia.
AB  - BACKGROUND: Acquired severe aplastic anemia is a rare and potentially fatal
      disease, which is characterized by hypocellular bone marrow and pancytopenia. The
      major signs and symptoms are severe infections, bleeding, and exhaustion. First
      line allogeneic hematopoietic stem cell transplantation (HSCT) of a human
      leukocyte antigen (HLA)-matched sibling donor (MSD) is a treatment for newly
      diagnosed patients with severe aplastic anemia. First-line treatment with
      ciclosporin and/or antithymocyte or antilymphocyte globulin (as first-line
      immunosuppressive therapy) is an alternative to MSD-HSCT and is indicated for
      patients where no MSD is found. OBJECTIVES: To evaluate the effectiveness and
      adverse events of first-line allogeneic hematopoietic stem cell transplantation
      of HLA-matched sibling donors compared to first-line immunosuppressive therapy
      including ciclosporin and/or antithymocyte or antilymphocyte globulin in patients
      with acquired severe aplastic anemia. SEARCH METHODS: We searched the electronic
      databases MEDLINE (Ovid), EMBASE (Ovid), and The Cochrane Library CENTRAL (Wiley)
      for published articles from 1946 to 22 April 2013. Further searches included
      trial registries, reference lists of recent reviews, and author contacts.
      SELECTION CRITERIA: The following prospective study designs were eligible for
      inclusion: randomized controlled trials (RCTs) and non-randomized controlled
      trials if the allocation of patients to treatment groups was consistent with
      'Mendelian randomization'. We included participants with newly diagnosed severe
      aplastic anemia who received MSD-HSCT or immunosuppressive therapy without prior
      HSCT or immunosuppressive therapy, and with a minimum of five participants per
      treatment group. We did not apply limits on publication year or languages. DATA
      COLLECTION AND ANALYSIS: Two review authors abstracted the data on study and
      patient characteristics and assessed the risk of bias independently. We resolved
      differences by discussion or by appeal to a third review author. The primary
      outcome was overall mortality. Secondary outcomes were treatment-related
      mortality, graft failure, no response to first-line immunosuppressive therapy,
      graft-versus-host-disease (GVHD), relapse after initial successful treatment,
      secondary clonal and malignant disease, health-related quality of life, and
      performance score. MAIN RESULTS: We identified three trials that met the
      inclusion criteria. None of these trials was a RCT. 302 participants are included
      in this review. The three included studies were prospectively conducted and had
      features consistent with the principle of 'Mendelian randomization' as defined in
      the present review. All studies had a high risk of bias due to the study design.
      All studies were conducted more than 10 years ago and may not be applicable to
      the standard of care of today. Primary and secondary outcome data showed no
      statistically significant difference between treatment groups. We present results
      for first-line allogeneic hematopoietic stem cell transplantation of an HLA
      matched sibling donor, which we denote as the MSD-HSCT group, versus first-line
      treatment with ciclosporin and/or antithymocyte or antilymphocyte globulin, which
      we denote as the immunosuppressive therapy group in the following section.The
      pooled hazard ratio for overall mortality for the MSD-HSCT group versus the
      immunosuppressive therapy group was 0.95 (95% confidence interval 0.43 to 2.12, P
      = 0.90, low quality evidence). Therefore, overall mortality was not statistically
      significantly different between the groups. Treatment-related mortality ranged
      from 20% to 42% for the MSD-HSCT group and was not reported for the
      immunosuppressive therapy group (very low quality evidence). The authors reported
      graft failure from 3% to 16% for the MSD-HSCT group and GVHD from 26% to 51%
      (both endpoints not applicable for the immunosuppressive therapy group, very low
      quality evidence). The authors did not report any data on response and relapse
      for the MSD-HSCT group. For the immunosuppressive therapy group, the studies
      reported no response from 15% (not time point stated) to 64% (three months) and
      relapse in one of eight responders after immunosuppressive therapy at 5.5 years
      (very low quality evidence). The authors reported secondary clonal disease or
      malignancies for the MSD-HSCT group versus the immunosuppressive therapy group in
      1 of 34 versus 0 of 22 patients in one study and in 0 of 28 versus 4 of 86
      patients in the other study (low quality evidence). None of the included studies
      addressed health-related quality of life. The percentage of the evaluated
      patients with a Karnofsky performance status score in the range of 71% to 100%
      was 92% in the MSD-HSCT group and 46% in the immunosuppressive therapy group.
      AUTHORS' CONCLUSIONS: There are insufficient and biased data that do not allow
      any conclusions to be made about the comparative effectiveness of first-line
      allogeneic hematopoietic stem cell transplantation of an HLA-matched sibling
      donor and first-line treatment with ciclosporin and/or antithymocyte or
      antilymphocyte globulin (as first-line immunosuppressive therapy). We are unable
      to make firm recommendations regarding the choice of intervention for treatment
      of acquired severe aplastic anemia.

PMID- 23881659
TI  - Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney
      function.
AB  - BACKGROUND: Hydroxyethyl starches (HES) are synthetic colloids commonly used for
      fluid resuscitation to replace intravascular volume, yet they have been
      increasingly associated with adverse effects on kidney function. This is an
      update of a Cochrane review first published in 2010. OBJECTIVES: To examine the
      effects of HES on kidney function compared to other fluid resuscitation therapies
      in different patient populations. SEARCH METHODS: We searched the Cochrane Renal
      Group's specialised register, the Cochrane Central Register of Controlled Trials
      (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, MetaRegister and reference
      lists of articles. The most recent search was completed on November 19, 2012.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in which
      HES was compared to an alternate fluid therapy for the prevention or treatment of
      effective intravascular volume depletion. Primary outcomes were renal replacement
      therapy (RRT), author-defined kidney failure and acute kidney injury (AKI) as
      defined by the RIFLE criteria. DATA COLLECTION AND ANALYSIS: Screening,
      selection, data extraction and quality assessments for each retrieved article
      were carried out by two authors using standardised forms. All outcomes were
      analysed using relative risk (RR) and 95% confidence intervals (95% CI). Authors
      were contacted when published data were incomplete. Preplanned sensitivity and
      subgroup analyses were performed after data were analysed with a random-effects
      model. MAIN RESULTS: This review included 42 studies (11,399 patients) including
      19 studies from the original review (2010), as well as 23 new studies. Fifteen
      studies were excluded from the original review (nine retracted from publication
      due to concerns about integrity of data and six lacking individual patient
      creatinine data for the calculation of RIFLE criteria). Overall, there was a
      significant increase in the need for RRT in the HES treated individuals compared
      to individuals treated with other fluid therapies (RR 1.31, 95% CI 1.16 to 1.49;
      19 studies, 9857 patients) and the number with author-defined kidney failure (RR
      1.59, 95% CI 1.26 to 2.00; 15 studies, 1361 patients). The RR of AKI based on
      RIFLE-F (failure) criteria also showed an increased risk of AKI in individuals
      treated with HES products (RR 1.14, 95% CI 1.01 to 1.30; 15 studies, 8402
      participants). The risk of meeting urine output and creatinine based RIFLE-R
      (risk) criteria for AKI was in contrast in favour of HES therapies (RR 0.95, 95%
      CI 0.91 to 0.99; 20 studies, 8769 patients). However, when RIFLE-R urine output
      based outcomes were excluded as per study protocol, the direction of AKI risk
      again favoured the other fluid type, with a non-significant RR of AKI in HES
      treated patients (RR 1.05, 95% CI 0.97 to 1.14; 8445 patients). A more robust
      effect was seen for the RIFLE-I (injury) outcome, with a RR of AKI of 1.22 (95%
      CI 1.08 to 1.37; 8338 patients). No differences between subgroups for the RRT and
      RIFLE-F based outcomes were seen between sepsis versus non-sepsis patients, high
      molecular weight (MW) and degree of substitution (DS) versus low MW and DS (>=
      200 kDa and > 0.4 DS versus 130 kDa and 0.4 DS) HES solutions, or high versus low
      dose treatments (i.e. >= 2 L versus < 2 L). There were differences identified
      between sepsis versus non-sepsis subgroups for the RIFLE-R and RIFLE-I based
      outcomes only, which may reflect the differing renal response to fluid
      resuscitation in pre-renal versus sepsis-associated AKI. Overall, methodological
      quality of the studies was good. AUTHORS' CONCLUSIONS: The current evidence
      suggests that all HES products increase the risk in AKI and RRT in all patient
      populations and a safe volume of any HES solution has yet to be determined. In
      most clinical situations it is likely that these risks outweigh any benefits, and
      alternate volume replacement therapies should be used in place of HES products.

PMID- 23881660
TI  - Respiratory muscle training for cervical spinal cord injury.
AB  - BACKGROUND: Cervical spinal cord injury (SCI) severely comprises respiratory
      function due to paralysis and impairment of the respiratory muscles. Various
      types of respiratory muscle training (RMT) to improve respiratory function for
      people with cervical SCI have been described in the literature. A systematic
      review of this literature is needed to determine the effectiveness of RMT (either
      inspiratory or expiratory muscle training) on pulmonary function, dyspnoea,
      respiratory complications, respiratory muscle strength, and quality of life for
      people with cervical SCI. OBJECTIVES: To evaluate the efficacy of RMT versus
      standard care or sham treatments in people with cervical SCI. SEARCH METHODS: We
      searched the Cochrane Injuries and Cochrane Neuromuscular Disease Groups'
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL) (2012, Issue 1), MEDLINE, EMBASE, CINAHL, ISI Web of Science, PubMed,
      and clinical trials registries (Australian New Zealand Clinical Trials Registry,
      ClinicalTrials, Controlled Trials metaRegister) on 5 to 8 March 2013. We
      handsearched reference lists of relevant papers and literature reviews. We
      applied no date, language, or publication restrictions. SELECTION CRITERIA: All
      randomised controlled trials that involved an intervention described as RMT
      versus a control group using an alternative intervention, placebo, usual care, or
      no intervention for people with cervical SCI were considered for inclusion. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected articles for
      inclusion, evaluated the methodological quality of the studies, and extracted
      data. We sought additional information from the trial authors when necessary. We
      presented results using mean differences (MD) (using post-test scores) and 95%
      confidence intervals (CI) for outcomes measured using the same scale or
      standardised mean differences (SMD) and 95% CI for outcomes measured using
      different scales. MAIN RESULTS: We included 11 studies with 212 participants with
      cervical SCI. The meta-analysis revealed a statistically significant effect of
      RMT for three outcomes: vital capacity (MD mean end point 0.4 L, 95% CI 0.12 to
      0.69), maximal inspiratory pressure (MD mean end point 10.50 cm/H2O, 95% CI 3.42
      to 17.57), and maximal expiratory pressure (MD mean end point 10.31 cm/H2O, 95%
      CI 2.80 to 17.82). There was no effect on forced expiratory volume in one second
      or dyspnoea. We could not combine the results from quality of life assessment
      tools from three studies for meta-analysis. Respiratory complication outcomes
      were infrequently reported and thus we could not include them in the meta
      analysis. Instead, we described the results narratively. We identified no adverse
      effects as a result of RMT in cervical SCI. AUTHORS' CONCLUSIONS: In spite of the
      relatively small number of studies included in this review, meta-analysis of the
      pooled data indicates that RMT is effective for increasing respiratory muscle
      strength and perhaps also lung volumes for people with cervical SCI. Further
      research is needed on functional outcomes following RMT, such as dyspnoea, cough
      efficacy, respiratory complications, hospital admissions, and quality of life. In
      addition, longer-term studies are needed to ascertain optimal dosage and
      determine any carryover effects of RMT on respiratory function, quality of life,
      respiratory morbidity, and mortality.

PMID- 23881661
TI  - Schedules for home visits in the early postpartum period.
AB  - BACKGROUND: Maternal complications including psychological and mental health
      problems and neonatal morbidity have been commonly observed in the postpartum
      period. Home visits by health professionals or lay supporters in the weeks
      following the birth may prevent health problems from becoming chronic with long
      term effects on women, their babies, and their families. OBJECTIVES: To assess
      outcomes for women and babies of different home-visiting schedules during the
      early postpartum period. The review focuses on the frequency of home visits, the
      duration (when visits ended) and intensity, and on different types of home
      visiting interventions. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (28 January 2013) and reference lists of
      retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs)
      (including cluster-RCTs) comparing different types of home-visiting interventions
      enrolling participants in the early postpartum period (up to 42 days after
      birth). We excluded studies in which women were enrolled and received an
      intervention during the antenatal period (even if the intervention continued into
      the postnatal period) and studies recruiting only women from specific high-risk
      groups. (e.g. women with alcohol or drug problems). DATA COLLECTION AND ANALYSIS:
      Study eligibility was assessed by at least two review authors. Data extraction
      and assessment of risk of bias were carried out independently by at least two
      review authors. Data were entered into Review Manager software. MAIN RESULTS: We
      included data from 12 randomised trials with data for more than 11,000 women. The
      trials were carried out in countries across the world, and in both high- and low
      resource settings. In low-resource settings women receiving usual care may have
      received no additional postnatal care after early hospital discharge.The
      interventions and control conditions varied considerably across studies with
      trials focusing on three broad types of comparisons: schedules involving more
      versus fewer postnatal home visits (five studies), schedules involving different
      models of care (three studies), and home versus hospital clinic postnatal check
      ups (four studies). In all but two of the included studies, postnatal care at
      home was delivered by healthcare professionals. The aim of all interventions was
      broadly to assess the wellbeing of mothers and babies, and to provide education
      and support, although some interventions had more specific aims such as to
      encourage breastfeeding, or to provide practical support.For most of our outcomes
      only one or two studies provided data, and overall results were
      inconsistent.There was no evidence that home visits were associated with
      improvements in maternal and neonatal mortality, and no strong evidence that more
      postnatal visits at home were associated with improvements in maternal health.
      More intensive schedules of home visits did not appear to improve maternal
      psychological health and results from two studies suggested that women receiving
      more visits had higher mean depression scores. The reason for this finding was
      not clear. There was some evidence that postnatal care at home may reduce infant
      health service utilisation in the weeks following the birth, and that more home
      visits may encourage more women to exclusively breastfeed their babies. There was
      some evidence that home visits are associated with increased maternal
      satisfaction with postnatal care. AUTHORS' CONCLUSIONS: Overall, findings were
      inconsistent. Postnatal home visits may promote infant health and maternal
      satisfaction. However, the frequency, timing, duration and intensity of such
      postnatal care visits should be based upon local needs. Further well designed
      RCTs evaluating this complex intervention will be required to formulate the
      optimal package.

PMID- 23881662
TI  - Telephone support for women during pregnancy and the first six weeks postpartum.
AB  - BACKGROUND: Telephone communication is increasingly being accepted as a useful
      form of support within health care. There is some evidence that telephone support
      may be of benefit in specific areas of maternity care such as to support
      breastfeeding and for women at risk of depression. There is a plethora of
      telephone-based interventions currently being used in maternity care. It is
      therefore timely to examine which interventions may be of benefit, which are
      ineffective, and which may be harmful. OBJECTIVES: To assess the effects of
      telephone support during pregnancy and the first six weeks post birth, compared
      with routine care, on maternal and infant outcomes. SEARCH METHODS: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (23 January 2013)
      and reference lists of all retrieved studies. SELECTION CRITERIA: We included
      randomised controlled trials, comparing telephone support with routine care or
      with another supportive intervention aimed at pregnant women and women in the
      first six weeks post birth. DATA COLLECTION AND ANALYSIS: Three review authors
      independently assessed studies identified by the search strategy, carried out
      data extraction and assessed risk of bias. Data were entered by one review author
      and checked by a second. Where necessary, we contacted trial authors for further
      information on methods or results. MAIN RESULTS: We have included data from 27
      randomised trials involving 12,256 women. All of the trials examined telephone
      support versus usual care (no additional telephone support). We did not identify
      any trials comparing different modes of telephone support (for example, text
      messaging versus one-to-one calls). All but one of the trials were carried out in
      high-resource settings. The majority of studies examined support provided via
      telephone conversations between women and health professionals although a small
      number of trials included telephone support from peers. In two trials women
      received automated text messages. Many of the interventions aimed to address
      specific health problems and collected data on behavioural outcomes such as
      smoking cessation and relapse (seven trials) or breastfeeding continuation (seven
      trials). Other studies examined support interventions aimed at women at high risk
      of postnatal depression (two trials) or preterm birth (two trials); the rest of
      the interventions were designed to offer women more general support and
      advice.For most of our pre-specified outcomes few studies contributed data, and
      many of the results described in the review are based on findings from only one
      or two studies. Overall, results were inconsistent and inconclusive although
      there was some evidence that telephone support may be a promising intervention.
      Results suggest that telephone support may increase women's overall satisfaction
      with their care during pregnancy and the postnatal period, although results for
      both periods were derived from only two studies. There was no consistent evidence
      confirming that telephone support reduces maternal anxiety during pregnancy or
      after the birth of the baby, although results on anxiety outcomes were not easy
      to interpret as data were collected at different time points using a variety of
      measurement tools. There was evidence from two trials that women at high risk of
      depression who received support had lower mean depression scores in the postnatal
      period, although there was no clear evidence that women who received support were
      less likely to have a diagnosis of depression. Results from trials offering
      breastfeeding telephone support were also inconsistent, although the evidence
      suggests that telephone support may increase the duration of breastfeeding. There
      was no strong evidence that women receiving telephone support were less likely to
      be smoking at the end of pregnancy or during the postnatal period.For infant
      outcomes, such as preterm birth and infant birthweight, overall, there was little
      evidence. Where evidence was available, there were no clear differences between
      groups. Results from two trials suggest that babies whose mothers received
      support may have been less likely to have been admitted to a neonatal intensive
      care unit (NICU), although it is not easy to understand the mechanisms
      underpinning this finding. AUTHORS' CONCLUSIONS: Despite some encouraging
      findings, there is insufficient evidence to recommend routine telephone support
      for women accessing maternity services, as the evidence from included trials is
      neither strong nor consistent. Although benefits were found in terms of reduced
      depression scores, breastfeeding duration and increased overall satisfaction, the
      current trials do not provide strong enough evidence to warrant investment in
      resources.

PMID- 23881663
TI  - Adipocytokine levels in women with anorexia nervosa. Relationship with weight
      restoration and disease duration.
AB  - OBJECTIVE: Starvation-induced depletion of fat stores in anorexia nervosa (AN) is
      known to be accompanied by alterations in some circulating adipocytokines. We
      analyzed a panel of circulating adipocytokines in women with AN compared with
      normal-weight controls and their relation with the disease duration and weight
      restoration. METHOD: We analyzed circulating adipocytokine levels in 28 patients
      with AN and in 33 normal-weight controls who were eating healthily. We determined
      by enzyme-linked immunosorbent assay the circulating levels of total and high
      molecular weight (HMW) adiponectin, lipocalin-2 (LCN2), leptin, tumor necrosis
      factor receptor-II (TNFRII), interleukin-6 (IL6), adipocyte fatty acid binding
      protein-4 (FABP4), ghrelin, and resistin. RESULTS: The two circulating forms of
      adiponectin are higher in AN women compared with controls. Both total and HMW
      adiponectin related negatively to the duration of the disease (r = -0.372, p =
      0.033; r = -0.450, p = 0.038, respectively). Furthermore, the lipid binding
      proteins LCN2 and FABP4 are lower in AN compared to the control group. Finally,
      leptin levels are lower in AN against controls and correlated positively with
      disease duration (r = 0.537, p = 0.007). Resistin, ghrelin, TNFRII, and IL6 have
      similar values in both groups, although TNFRII and ghrelin related negatively to
      body mass index variation at the end of treatment (r = -0.456, p = 0.039; r = 
      0.536, p = 0.015, respectively). DISCUSSION: These results suggest there is a
      need to investigate if changes in adipocytokine levels could serve as weight
      restoration biomarkers. Further studies are warranted to elucidate the specific
      role of these molecules in the timing of weight restoration.

PMID- 23881664
TI  - Design, synthesis, and antihyperlipidemic evaluation of novel 2-[1
      (substitutedphenyl)-4-oxo-azetidin-2-yl]-5,6-disubstitutedthieno[2,3-d]pyrimidin
      4(3H)-ones.
AB  - Novel thienopyrimidine derivatives of azetidinone possessing the combined
      features of the cholesterol absorption inhibitor drug ezetimibe and potential
      antihyperlipidemic 2-substitutedthienopyrimidin-4-ones were synthesized and
      characterized by spectroscopic data and elemental analysis. These compounds were
      evaluated for their lipid-lowering activity in Wistar albino rats. Some of them
      showed significant lipid-lowering effects comparable to those of the standard
      drug, gemfibrozil, at the same dose levels. 

PMID- 23881665
TI  - Acotiamide: first global approval.
AB  - Acotiamide (Acofide((r))), an oral first-in-class prokinetic drug, is under
      global development by Zeria Pharmaceutical Co. Ltd and Astellas Pharma Inc. for
      the treatment of patients with functional dyspepsia. The drug modulates upper
      gastrointestinal motility to alleviate abdominal symptoms resulting from
      hypomotility and delayed gastric emptying. It exerts its activity in the stomach
      via muscarinic receptor inhibition, resulting in enhanced acetylcholine release
      and inhibition of acetylcholinesterase activity. Unlike other prokinetic drugs
      that are utilized in the management of functional dyspepsia, acotiamide shows
      little/no affinity for serotonin or dopamine D2 receptors. Acotiamide is the
      world's first approved treatment for functional dyspepsia diagnosed by Rome III
      criteria, with its first approval occurring in Japan. Phase III trials in this
      patient population are in preparation in Europe, with phase II trials completed
      in the USA and Europe. This article summarizes the milestones in the development
      of acotiamide, leading to its first approval for use in patients with functional
      dyspepsia. 

PMID- 23881668
TI  - Dabrafenib: first global approval.
AB  - Dabrafenib (Tafinlar(r)), a mutant-BRAF kinase inhibitor, emerged from
      GlaxoSmithKline's research programme for the discovery of selective inhibitors of
      mutant BRAF kinase activity, for the treatment of solid tumours; mutations in the
      BRAF gene are associated with increased growth and proliferation of cancer cells.
      GlaxoSmithKline has focused the development of dabrafenib on the treatment of
      malignant melanoma, as BRAF mutations are present in 50 % of these cancers.
      Dabrafenib is approved in the US as a single agent treatment for unresectable or
      metastatic melanoma in patients with the BRAF V600E mutation, and has received a
      positive opinion in the EU in this indication. Submissions have also been made in
      the US and the EU for the use of dabrafenib in combination with trametinib for
      the treatment of metastatic melanoma with a BRAF V600E/K mutation. Global phase
      III development of dabrafenib as a monotherapy and as a combination therapy is
      ongoing in the treatment of malignant melanoma. Phase II development is ongoing
      for the treatment of malignant melanoma that has metastasised to the brain, and
      for colorectal and non-small cell lung cancers. Dabrafenib is intended to treat
      the patient population with a BRAF V600E/K mutation. GlaxoSmithKline's dabrafenib
      application in the US included the treatment of this population as detected by a
      US FDA-approved test. GlaxoSmithKline, in collaboration with bioMerieux and
      Response Genetics, has developed a molecular theranostic test to identify BRAF
      V600E/K mutations. Pre-Market approval of the test has been granted by the FDA.
      This article summarises the milestones in the development of dabrafenib leading
      to this first approval as a single agent treatment for unresectable or metastatic
      melanoma in patients with the BRAF V600E mutation. 

PMID- 23881667
TI  - Treatment of opioid-induced constipation: focus on the peripheral MU-opioid
      receptor antagonist methylnaltrexone.
AB  - Most prescribed opioids exert their analgesic effects via activation of central
      MU-opioid receptors. However, MU-opioid receptors are also located in the
      gastrointestinal (GI) tract, and activation of these receptors by opioids can
      lead to GI-related adverse effects, in particular opioid-induced constipation
      (OIC). OIC has been associated with increased use of healthcare resources,
      increased healthcare costs, and decreased quality of life for patients.
      Nonpharmacologic (e.g., increased fiber uptake) and pharmacologic agents (e.g.,
      laxatives) may be considered for the treatment and prevention of OIC. However,
      many interventions, such as laxatives alone, are generally insufficient to
      reverse OIC because they do not target the underlying cause of OIC, opioid
      activation of MU-opioid receptors in the GI tract. Therefore, there has been keen
      interest in antagonism of the MU-opioid receptor in the periphery to inhibit the
      effects of opioids in the GI tract. In this review, currently available
      pharmacologic therapies for the treatment and prevention of OIC are summarized
      briefly, with a primary focus on the administration of the peripheral MU-opioid
      receptor antagonist methylnaltrexone bromide in patients with OIC and advanced
      illness who are receiving palliative care. Also, clinical trial data of
      methylnaltrexone treatment in patients with OIC and other pain conditions (i.e.,
      chronic noncancer pain and pain after orthopedic surgery) are reviewed. Data
      support that methylnaltrexone is efficacious for the treatment of OIC and has a
      favorable tolerability profile. 

PMID- 23881666
TI  - Extra-esophageal manifestations of gastroesophageal reflux disease: diagnosis and
      treatment.
AB  - Gastroesophageal reflux disease (GERD) is a common disease that is often
      diagnosed based on typical symptoms of heartburn and regurgitation. In addition
      to these more classic manifestations, GERD is increasingly associated with extra
      esophageal symptoms, including chronic cough, asthma, laryngitis, and dental
      erosions. Due to the poor sensitivity of endoscopy and pH monitoring, and the
      poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors
      (PPIs) is now considered the initial diagnostic step in patients suspected of
      having GERD-related symptoms. For those who improve with PPIs, GERD is the
      presumed etiology, but for those who remain unresponsive to such therapy, further
      diagnostic testing with impedance/pH monitoring may be necessary in order to
      exclude refractory acid or weakly acid reflux. In those with normal test results
      despite PPI therapy and continued symptoms, causes other than GERD may be
      pursued. Recent data suggest that in patients with extra-esophageal symptoms,
      objective findings of moderate-sized hiatal hernia and moderate reflux on pH
      testing may predict response to acid suppressive therapy. PPI-unresponsive
      patients usually have causes other than GERD for their extra-esophageal symptoms
      and continued PPI therapy in this group is not recommended. 

PMID- 23881670
TI  - Spatial analysis of amyotrophic lateral sclerosis in Northern New England, USA,
      1997-2009.
AB  - INTRODUCTION: An environmental trigger of sporadic amyotrophic lateral sclerosis
      (ALS) is supported by geographic disparities in ALS incidence and development of
      the disease in conjugal couples. This study aims to investigate the incidence of
      ALS in the Northern New England states of New Hampshire (NH), Vermont (VT), and
      Maine (ME). METHODS: We reviewed medical records and community databases to
      identify dwelling addresses of 688 patients diagnosed with ALS in 1997-2009 in
      NH, VT, and ME. We used spatial analysis to identify clusters of census block
      groups with statistically significant high incidence. RESULTS: We identified 11
      clusters of statistically significant high incidence, each containing 6 or more
      cases of ALS. These 11 clusters are grouped in 4 distinct regions. CONCLUSIONS:
      There appear to be areas of significant spatial clustering within Northern New
      England. Further analysis will be needed to confirm whether there is any
      correlation between these areas and potential environmental risk factors.

PMID- 23881669
TI  - Eplerenone: a review of its use in patients with chronic systolic heart failure
      and mild symptoms.
AB  - Eplerenone (Inspra(r)) is a selective mineralocorticoid receptor antagonist
      (MRA). In the EU, it is approved for use (in addition to standard optimal
      therapy) to reduce the risk of cardiovascular (CV) mortality and morbidity in
      adult patients with chronic systolic heart failure (HF) and mild symptoms. This
      article reviews the efficacy and tolerability of eplerenone in this indication
      and briefly summarizes its pharmacology. In the EMPHASIS-HF study, relative to
      placebo, the addition of eplerenone to optimal background therapy significantly
      reduced the risk of death from CV causes or hospitalization for HF in patients
      with chronic systolic HF and mild symptoms. Benefits of eplerenone therapy over
      placebo were also observed in several secondary outcomes, including: death from
      any cause or hospitalization for HF; death from any cause; hospitalization for
      any reason; or hospitalization for HF. Eplerenone was generally well tolerated in
      this study, with the most frequent adverse event being hyperkalaemia, which is a
      known adverse event of the drug class. Sexual adverse events (e.g. gynecomastia)
      occurred in <1 % of eplerenone recipients, reflecting the selectivity of
      eplerenone for mineralocorticoid receptors. Based on these results, European
      guidelines have been updated and recommend the use of an MRA to reduce the risk
      of HF hospitalization and premature death in all patients with persisting
      symptoms (New York Heart Association class II-IV) and a left-ventricular ejection
      fraction of <=35 %, despite treatment with ACE inhibitor (or an angiotensin
      receptor blocker if an ACE inhibitor is not tolerated) and a beta-blocker.

PMID- 23881671
TI  - What does H7N9 mean and how can we be prepared for the next flu pandemic?

PMID- 23881672
TI  - Adenovirus sneak attacks during the H7N9 flu season.

PMID- 23881673
TI  - Transition metal complexes of a salen-fullerene diad: redox and catalytically
      active nanostructures for delivery of metals in nanotubes.
AB  - A covalently-linked salen-C60 (H2L) assembly binds a range of transition metal
      cations in close proximity to the fullerene cage to give complexes [M(L)] (M=Mn,
      Co, Ni, Cu, Zn, Pd), [MCl(L)] (M=Cr, Fe) and [V(O)L]. Attaching salen covalently
      to the C60 cage only marginally slows down metal binding at the salen
      functionality compared to metal binding to free salen. Coordination of metal
      cations to salen-C60 introduces to these fullerene derivatives strong absorption
      bands across the visible spectrum from 400 to 630 nm, the optical features of
      which are controlled by the nature of the transition metal. The redox properties
      of the metal-salen-C60 complexes are determined both by the fullerene and by the
      nature of the transition metal, enabling the generation of a wide range of
      fullerene-containing charged species, some of which possess two or more unpaired
      electrons. The presence of the fullerene cage enhances the affinity of these
      complexes for carbon nanostructures, such as single-, double- and multiwalled
      carbon nanotubes and graphitised carbon nanofibres, without detrimental effects
      on the catalytic activity of the metal centre, as demonstrated in styrene
      oxidation catalysed by [Cu(L)]. This approach shows promise for applications of
      salen-C60 complexes in heterogeneous catalysis.

PMID- 23881674
TI  - Inhibition of Wnt/beta-catenin signaling promotes engraftment of mesenchymal stem
      cells to repair lung injury.
AB  - We sought to explore the treatment effects and the repair mechanisms of bone
      marrow derived mesenchymal stem cells (MSCs) during HCl-induced acute lung injury
      (ALI). MSCs were delivered through the tail veins of rats 24 h after intranasal
      instillation of HCl. The results showed that MSCs did not ameliorate the
      histopathologic changes of ALI and pulmonary fibrosis. We found that the
      activated Wnt/beta-catenin signaling may regulate the differentiation of MSCs and
      is associated with lung fibroblasts activation, pulmonary fibrosis and tissue
      repair process in ALI rats. Immunofluorescence and histology analysis indicated
      that activated canonical Wnt/beta-catenin signaling induced most MSCs to
      differentiate into myofibroblasts or fibroblasts in vivo. However, inhibition of
      Wnt/beta-catenin signaling by Dickkopf-1 (DKK1) promotes epithelial
      differentiation of MSCs induced by native alveolar epithelial cells which are
      beneficial to repair the injured lung epithelium. Inhibition of Wnt/beta-catenin
      signaling after MSCs transplantation ameliorated pulmonary fibrosis and improved
      pulmonary function which attenuated the lung injury. In vitro study, activation
      of the Wnt/beta-catenin signaling stimulated MSCs to express myofibroblasts
      markers, which was attenuated by DKK1. Furthermore, Wnt3alpha activated Wnt/beta
      catenin signaling in lung fibroblasts to enhance the expression of collagen I,
      vimentin and alpha-smooth muscle actin, but DKK1 attenuated these proteins
      expression. These findings demonstrated that canonical Wnt/beta-catenin signaling
      plays a key role in regulating differentiation of MSCs in vivo or in vitro and
      the pathogenesis of fibrotic diseases. Our study suggested that inhibition of
      abnormal activated Wnt/beta-catenin signaling would promote MSCs epithelial
      differentiation to repair lung injury and reduce pulmonary fibrosis.

PMID- 23881675
TI  - An evaluation of circulating bovine viral diarrhea virus type 2 maternal antibody
      level and response to vaccination in Angus calves.
AB  - Vaccination against viruses has been shown to help prevent bovine respiratory
      disease in cattle. However, both passively acquired maternal antibody
      concentration and calf age have been shown to impact the ability of the immune
      system of a calf to respond to vaccination. The objectives of this study were to
      identify and evaluate environmental and management factors that affect 1)
      passively acquired bovine viral diarrhea virus (BVDV) type 2 antibody level, 2)
      decay rate of passively acquired BVDV type 2 antibody level, and 3) responses to
      BVDV type 2 vaccinations. A 2-shot modified live vaccine was administered to
      1,004 Angus calves that were weaned at either the initial vaccination (n = 508)
      or the booster vaccination (n = 496). Calves weaned at the initial vaccination
      averaged 139 d whereas calves weaned at booster vaccination averaged 128 d of
      age. Bovine viral diarrhea virus type 2 antibodies were measured in 3
      approximately 21-d intervals, serially collected serum samples to quantify
      antibody levels at initiation and end of vaccination protocol in addition to
      responses to initial, booster, and overall vaccination protocol. Amount of
      passively transferred antibody in the calf increased as dam age increased from 2
      to 6 yr (P < 0.05) with no differences after dams reached 6 yr (P > 0.05). Calf
      age nested within birth year-season and dam age affected both initial and final
      antibody level, initial response, booster response, and overall antibody response
      to vaccination. The level of circulating, passively acquired maternal antibodies
      present at the time of vaccination had a significant (P < 0.05) negative effect
      on antibody responses to vaccination (initial response, booster response, and
      overall response). Calves that were weaned at the time of initial vaccination had
      significantly (P < 0.05) greater final antibody level, initial response, and
      overall response to vaccination than animals weaned at booster vaccination. In
      order for a calf to mount an overall antibody response to vaccination, maternal
      antibodies in circulation need to be less than 3.12 titers. However, the age at
      which a calf reached this antibody threshold was dependent on dam age. This
      information will help cattle managers and consultants design vaccination
      protocols to successfully mount an antibody response to vaccination. 

PMID- 23881676
TI  - Effect of pig breed and dietary protein level on selected fatty acids and
      stearoyl-coenzyme A desaturase protein expression in longissimus muscle and
      subcutaneous fat.
AB  - The aims of the study were 1) to investigate effects of a low protein diet on
      fatty acids content and composition of the LM and subcutaneous adipose tissue in
      3 genetically diverse breeds, Large White * Landrace, Alentejano, and Bizaro, and
      2) to determine whether the effect of the low protein diet of fatty acid
      composition is associated with dietary modulation of stearoyl-CoA desaturase
      (SCD) protein expression. The experiments were conducted on 12 Large White *
      Landrace, 12 Alentejano, and 10 Bizaro female and male pigs. The average animal
      BW at the beginning of experiments was 40.8, 40.7, and 38.3 kg for Large White *
      Landrace, Alentejano, and Bizaro, respectively, and the BW of animals at
      slaughter was 90 kg. The diets contained 202 or 169 g/kg DM of CP (high and low
      protein diets, respectively) and were balanced in essential AA. The diets were
      fed until the animals reached 90 kg BW (approximately 73 d). It was established
      that Large White * Landrace pigs had a less (P = 0.001) total fatty acid content
      in subcutaneous adipose tissue when compared with Alentejano and Bizaro and less
      (P < 0.001) intramuscular fat (IMF) content when compared with Alentejano. There
      was a positive relationship between SCD protein expression in the LM and MUFA
      content (r = 0.627, P = 0.029) and SCD protein expression and total muscle fatty
      acids content (r = 0.725, P = 0.008) in Large White * Landrace but not in
      Alentejano and Bizaro breeds. It has been suggested that SCD protein expression
      is associated with regulation of fat deposition only in breeds with genetic
      predisposition to a low IMF content. 

PMID- 23881677
TI  - Effects of added chelated trace minerals, organic selenium, yeast culture, direct
      fed microbials, and Yucca schidigera extract in horses: II. Nutrient excretion
      and potential environmental impact.
AB  - The objective of this study was to test the hypothesis that an equine diet
      formulated with chelated trace minerals, organic selenium, yeast culture, direct
      fed microbials (DFM) and Yucca schidigera extract would decrease excretion of
      nutrients that have potential for environmental impact. Horses were acclimated to
      100% pelleted diets formulated with (ADD) and without (CTRL) the aforementioned
      additives. Chelated sources of Cu, Zn, Mn, and Co were included in the ADD diet
      at a 100% replacement rate of sulfate forms used in the CTRL diet. Additionally,
      the ADD diet included organic selenium yeast, DFM, and Yucca schidigera extract.
      Ten horses were fed the 2 experimental diets during two 42-d periods in a
      crossover design. Total fecal and urine collection occurred during the last 14 d
      of each period. Results indicate no significant differences between Cu, Zn, Mn,
      and Co concentrations excreted via urine (P > 0.05) due to dietary treatment.
      There was no difference between fecal Cu and Mn concentrations (P > 0.05) based
      on diet consumed. Mean fecal Zn and Co concentrations excreted by horses
      consuming ADD were greater than CTRL (P < 0.003). Differences due to diet were
      found for selenium fecal (P < 0.0001) and urine (P < 0.0001) excretions, with
      decreased concentrations found for horses consuming organic selenium yeast (ADD).
      In contrast, fecal K (%) was greater (P = 0.0421) for horses consuming ADD,
      whereas concentrations of fecal solids, total N, ammonia N, P, total ammonia, and
      fecal output did not differ between dietary treatments (P > 0.05). In feces
      stockpiled to simulate a crude composting method, no differences (P > 0.05) due
      to diet were detected for particle size, temperature, moisture, OM, total N, P,
      phosphate, K, moisture, potash, or ammonia N (P > 0.05). Although no difference
      (P = 0.2737) in feces stockpile temperature due to diet was found, temperature
      differences over time were documented (P < 0.0001). In conclusion, the addition
      of certain chelated mineral sources, organic Se yeast, DFM, and Yucca schidigera
      extract did not decrease most nutrient concentrations excreted. Horses consuming
      organic selenium as part of the additive diet had lower fecal and urine Se
      concentrations, as well as greater fecal K concentrations. 

PMID- 23881678
TI  - Effect of postweaning diet on ovarian development and fertility in replacement
      beef heifers.
AB  - Programs for developing replacement heifers are designed for heifers to calve at
      2 yr of age and to extend their stayability in the herd and minimize feed cost.
      The experimental objective was to determine whether developing prepubertal
      heifers on less dietary energy and to a BW of 55% rather than 65% of mature BW at
      14 mo of age would compromise ovarian development and reduce fertility. In a 3-yr
      study, 8-mo-old Angus (n = 60/yr) and composite MARC II (n = 60/yr) heifers were
      assigned equally by age, BW, and breed to receive either a low (LG) or high (HG)
      BW gain diet fed to achieve an ADG of either 0.45 or 0.8 kg/d from 8 to 15 mo of
      age, including the first 21 d of breeding, and then transferred to pasture. At 14
      mo, heifers were housed with fertile bulls for 47 d. Estrus was monitored for 21
      d. Within 12 h after detection of estrus, ovarian length and height, preovulatory
      follicle diam., and antral follicle count (AFC) were measured by transrectal
      ultrasonography. Corpus luteum (CL) volume and plasma progesterone concentration
      were measured 5 to 15 d after estrus. Data were analyzed by ANOVA with treatment,
      breed, and year and their 2-way interactions as independent variables. At
      breeding, HG heifers were heavier than LG heifers (419.9 vs. 361.8 +/- 7.5 kg; P
      < 0.01); ADG for the treatment period was 0.79 vs. 0.47 +/- 0.04 kg/d (P < 0.01),
      respectively. In 2010 and 2011, 97.2% of heifers were cyclic by 21 d of breeding.
      Size of the ovary, preovulatory follicle, CL, and AFC did not differ between HG
      and LG, but preovulatory follicle diam. and ovarian length were greater (P <=
      0.05) for MARC II vs. Angus heifers. Progesterone concentrations were less for LG
      vs. HG heifers (P <= 0.02), whereas CL volume was not affected by treatment or
      breed but was correlated positively with preovulatory follicle size (P < 0.01).
      Total AFC ranged from 5 to 49 and was correlated positively with ovarian volume
      but was not associated with fertility. A greater proportion of HG vs. LG heifers
      conceived within the first 21 d of the breeding period (64.4% vs. 49.2% +/- 3.8%,
      respectively; P < 0.01), but overall pregnancy rate was not affected by treatment
      (83.0% vs. 77.7% +/- 3.1%, respectively; P > 0.10). Pregnancy rate was 10% less
      (P < 0.01) for Angus vs. MARC II heifers. Developing beef heifers at a lesser ADG
      to a lighter BW (55% vs. 64% of mature BW) at breeding did not influence
      postweaning ovarian development or AFC or compromise pregnancy rate during the 47
      d breeding period. 

PMID- 23881679
TI  - Subspecies differences in early fetal development and plasma pregnancy-associated
      glycoprotein concentrations in cattle.
AB  - Inclusion of Bos indicus genetics improves production traits of cattle maintained
      in hot climates. Limited information exists detailing pregnancy-specific events
      as influenced by variable amounts of Bos indicus genetics. Three experiments were
      completed to examine the effect of Bos taurus and Bos indicus genotypes on fetal
      size and plasma pregnancy-associated glycoprotein (PAG) concentrations. In all
      experiments, cows were bred by AI after synchronization of ovulation. Fetal
      measurements were completed by transrectal ultrasonography and plasma PAG
      concentrations were quantified from plasma harvested the day of each fetal
      measurement. In Exp. 1, fetal size and plasma PAG concentrations were measured at
      d 53 of pregnancy in cows composed of various fractions of Angus and Brahman (n =
      9 to 21 cows/group). Fetus size was greater in cows containing >80% Angus
      genetics compared with cows containing <80% Angus influence (3.40 +/- 0.28 vs.
      2.86 +/- 0.28 cm crown-rump length; P < 0.01). Plasma PAG concentrations were
      reduced (P < 0.01) in cows containing >80% Angus genetics when compared with
      their contemporaries (6.0 +/- 1.5 ng/mL vs. 9.4 +/- 1.5 ng/mL). In Exp. 2, fetal
      measurements and plasma PAG concentrations were determined at d 35 and 62 of
      pregnancy in Angus and Brangus cows. Breed did not affect fetus size at d 35, but
      Angus cows contained larger fetuses than Brangus cows at d 62 [3.0 +/- 0.03 vs.
      2.8 +/- 0.03 cm crown-nose length (CNL; P > 0.01)]. Plasma PAG concentrations
      were not different between breed at d 35 and 62 (P > 0.1). In Exp. 3, fetal
      measurements and plasma samples were collected at d 33/34, 40/41, 47/48, and
      54/55 post-AI in Angus and Brangus cows. Fetus size was not different (P > 0.05)
      between genotypes on d 33/34, 40/41, and 47/48. Angus fetuses were larger than
      Brangus fetuses at d 54/55 (2.1 +/- 0.03 vs. 1.9 +/- 0.03 cm CNL; P = 0.001).
      Plasma PAG concentrations were less in Angus than Brangus cows at each time point
      (average 4.9 +/- 0.9 vs. 8.2 +/- 0.9 ng/mL; P = 0.005). In conclusion, these
      studies determined that the Bos taurus * Bos indicus genotype impacts fetal size
      and rate of fetal development by 7 wk of gestation. Plasma PAG concentrations
      were increased in cattle with Bos indicus genetics in 2 of 3 studies, suggesting
      that genotype is one of several determinants of PAG production and secretion in
      cattle. 

PMID- 23881680
TI  - Utilization of crystalline or protein-bound lysine for growth and carcass traits
      of barrows and gilts fed individually or in groups.
AB  - An experiment consisting of two 4-wk trials was conducted to determine Lys use
      for growth and carcass traits in barrows and gilts fed individually or in groups.
      One hundred twelve growing pigs (56 barrows and 56 gilts; average initial BW of
      18.6 kg) were used in each trial. Pigs were fed individually or in groups of 3.
      There were 28 pigs individually penned, and 84 pigs in 28 pens (3 pigs/pen).
      There were 2 replications per treatment in each trial for a total of 4
      replications. Dietary treatments consisted of a corn-soybean meal (SBM) basal
      diet (0.48% Lys) and diets containing 0.56%, 0.65%, and 0.74% standardized ileal
      digestible (SID) Lys that were achieved by adding Lys to the basal diet from
      either SBM or crystalline source as L-Lys HCL (CLys). At the end of each trial,
      all pigs were scanned using real-time ultrasound to determine 10th-rib back fat
      depth and LM area, and fat-free lean gain (FFLG) was calculated. Blood samples
      were taken from all pigs weekly to determine plasma urea N (PUN). Pigs fed CLys
      and Lys from SBM were not different in final BW, ADG, ADFI, or G:F. The ADG and
      G:F increased linearly (P < 0.01) as dietary Lys concentration increased. The SID
      Lys intake increased linearly (P < 0.01) as dietary Lys concentration increased
      and was not different when comparing pigs fed diets with CLys or SBM. The amount
      of SID Lys required per unit of growth or BW gain increased linearly (about 13 to
      15.50 g/kg) in pigs fed either CLys or SBM Lys. Pigs fed individually had a
      greater (P < 0.05) ADG (0.59 vs. 0.57 kg) and ADFI (1.36 vs. 1.29 kg) than pigs
      fed in groups. The SID Lys intake was greater (P < 0.05) in pigs fed individually
      in comparison with pigs fed in a group (8.51 vs. 8.06 g/d). Fat-free lean gain
      and LM area increased (P < 0.01) as dietary Lys concentration increased
      regardless of Lys source. Pigs fed CLys diets had a greater (P < 0.05) LM area
      than pigs fed SBM at 0.74% SID Lys. Gilts had a greater (P < 0.01) LM area (14.28
      vs. 13.58 cm(2)) and FFLG (264 vs. 245 g/d) than barrows. Pigs fed individually
      with CLys had less (P < 0.01) PUN than pigs fed Lys from SBM. Barrows fed
      individually had less (sex * feeding method, P < 0.01) PUN than gilts (26.75 vs.
      29.32 g/100 mL). The results indicate that Lys from SBM-bound and CLys source
      were utilized similarly for growth and carcass traits regardless of sex or
      feeding method. 

PMID- 23881681
TI  - Genome-wide association study of concentrations of iron and other minerals in
      longissimus muscle of Angus cattle.
AB  - The objective of this study was to characterize variation and identify SNP and
      chromosomal regions associated with mineral concentrations in LM of Angus beef
      cattle. Samples of LM from 2,285 Angus cattle were obtained, and concentrations
      of 7 minerals, including iron, magnesium, manganese, phosphorus, potassium,
      sodium, and zinc, were quantified. Genomic DNA extracted from the ground beef
      sample used for mineral composition was genotyped with the Bovine SNP50 Infinium
      II BeadChip, and effects of SNP on each trait were estimated using the Bayes-Cpi
      module of GenSel software. Pedigree-based estimates of heritabilities and
      corresponding genetic variances indicate iron was the only mineral concentration
      that could be considered a good candidate for manipulation by genomic selection.
      The amount of variation that could be accounted for by SNP genotypes was
      concordant with pedigree-based heritabilities and varied from very low for
      potassium and sodium (<0.09) to medium high (0.37) for iron. Although significant
      chromosomal regions were identified for all minerals analyzed in this study,
      further study focused on iron. Seven regions on 6 chromosomes (1, 2, 7, 10, 15,
      and 28) were identified to have a major effect on the iron content of LM in Angus
      cattle. The accuracy of direct genomic values (DGV) for iron concentration was
      estimated using a 5-fold cross-validation strategy. The accuracy of DGV estimated
      as the genetic correlation between DGV and the phenotype (iron concentration)
      adjusted for contemporary groups was 0.59. A bivariate animal model was used to
      estimate genetic correlations between iron concentrations and a reduced set of
      economically important carcass traits: HCW, rib eye area, calculated USDA yield
      grade, percent KPH, and marbling score. The genetic correlations between iron
      concentration and HCW, percentage KPH, marbling score, and rib eye area were
      small (-0.19 to 0.15) and nonsignificant. Although still weak (0.22), a positive
      significant genetic correlation was identified between iron content and USDA
      calculated yield grade. Beef is a major contributor of iron and zinc in the human
      diet, and this study found that iron content might be effectively manipulated
      through marker-assisted selection programs, without compromising other carcass
      and palatability traits. 

PMID- 23881682
TI  - Genetic correlations between lactation performance and growing-finishing traits
      in pigs.
AB  - Genetic selection for increased litter size of sows increases the risk of a large
      negative energy balance during lactation. Furthermore, the feed intake capacity
      of the lactating sows might be reduced due to the simultaneous selection for
      greater feed efficiency during the growth phase when sows were actually reared as
      finishers but later on selected for breeding. There is a need to improve
      lactation performance of sows and continue selection for feed efficiency of
      grower-finishers in commercial breeding. Therefore, this study was conducted to
      estimate genetic correlations between growing-finishing traits and lactation
      performance traits. An additional objective was to study the impact of including
      additive social effects in the animal model on genetic correlation estimates.
      Analyses were performed on a population of 1,149 commercial crossbred sows with
      repeated observations on lactation performance traits and their 7,723 grower
      finisher offspring. The genetic correlation between daily BW gain of grower
      finishers and starting BW of lactating sows was positive (rg = 0.24; P < 0.05).
      The correlation between off-test backfat of grower-finishers and fat mass of
      lactating sows was also positive (rg = 0.53; P < 0.05). The genetic regulation of
      feed intake from the beginning of lactation seems to differ from the genetic
      regulation of feed intake during the growing-finishing period, as the correlation
      between these 2 traits was low (rg = +0.23; P < 0.05). Feed efficiency during
      growing-finishing and lactation phases showed similar tendencies as the genetic
      correlation between residual feed intake of the grower-finisher and lactation
      efficiency of sows was -0.51 (P < 0.05). Taking heritable social effects into
      account for daily BW gain and feed intake did not affect the genetic correlation
      estimates, either within growing-finishing traits or between growing-finishing
      traits and lactation performance traits. It was concluded that in the absence of
      antagonistic genetic correlations, selection for growing-finishing traits in dam
      lines could be combined with selection for lactation performance traits. 

PMID- 23881683
TI  - Longitudinal study of the effect of rubber slat mats on locomotory ability, body,
      limb and claw lesions, and dirtiness of group housed sows.
AB  - This study evaluated the influence of floor type on sow welfare with particular
      focus on lameness, claw lesions (CL), and injuries. The study used 164 gilts
      housed in groups of 8 from AI to 110 d of pregnancy in pens with concrete (n =
      84) slatted floor left uncovered or covered by 10-mm rubber slat mats (n = 80)
      through 2 parities. Lameness (0 = normal to 5 = severe), limb (0 = normal to 6 =
      severe) and body (0 = normal to 5 = severe) lesions, and manure on the body (MOB;
      score 0 to 2) were recorded at AI, 24 to 72 h postmixing, between 50 and 70 d of
      pregnancy, and 2 wk before farrowing. Claw lesions (score 0 = normal to 3 =
      severe) were recorded at AI and between 50 and 70 d of pregnancy. The dirtiness
      and wetness of the floors was scored weekly (score 0 = clean to 4 = >75% of the
      pen soiled/wet). Data from the first and second parities were analyzed
      separately. Sows were categorized as nonlame (score <= 1) or lame (score >= 2).
      Median (M(e)) scores were calculated for CL and body and limb lesions and were
      classified as less than or equal to the median or greater than the median lesion
      scores. Sows on rubber slat mats had a reduced risk of lameness during both
      parities (P < 0.01) compared with sows on concrete. They also had an increased
      risk of scores greater than the median for toe overgrowth (M(e) = 2 and M(e) = 3
      in the first and second parity, respectively) and heel sole crack (HSC; M(e) = 3)
      during both parities (P < 0.01) and for cracks in the wall (CW; M(e) = 4) and
      white line damage (WL; M(e) = 4; P < 0.01) in the first and second parity,
      respectively. There was a reduced risk of lameness in sows with scores greater
      than the median for HSC (P = 0.05) in the first parity and WL (M(e) = 3; P <
      0.01) and CW (M(e) = 3; P < 0.05) in the second parity. Wounds (M(e) = 3) and
      severe lesions (M(e) = 0) on the limbs with scores greater than the median were
      associated with an increased risk of lameness (P < 0.01) in the first and second
      parity, respectively. Sows on rubber slat mats had a reduced risk of scores
      greater than the median for swellings (M(e) = 4) and wounds (P < 0.01) during
      both parities. Pens with rubber slat mats were dirtier than uncovered pens (P <
      0.01); however, there was no association between MOB and flooring type. There was
      also no association between body lesion score and flooring type. In this study,
      CL were not associated with an increased risk of lameness. Therefore, even though
      rubber slat mats were associated with an increased risk of CL, they improved the
      welfare of group housed sows by reducing the risk of lameness and limb lesions.

PMID- 23881684
TI  - Comparison of ileal and total tract nutrient digestibility of dry dog foods.
AB  - The apparent total tract and ileal digestibility assays to measure AA absorption
      in commercial canine diets were compared in the present study. Five ileal
      cannulated dogs were fed 5 commercial dry canine foods selected to contain 19 to
      30% CP in a 5 * 5 Latin square design. Ileal and total tract digestibility
      (apparent and standardized) of DM, OM, CP, crude fat (CF), carbohydrate, and AA
      (including reactive Lys) were calculated using Cr2O3 as an indigestible marker.
      Greater apparent total tract digestibility values were found for DM, OM, and CP
      (P <= 0.034) compared with ileal digestibility values; however, CF (P = 0.058)
      had a greater ileal apparent digestibility. Apparent and standardized CP
      digestibility values were, respectively, 5.7 and 7.4 percentage units greater
      when measured over the total digestive tract compared with measurement at the
      ileum (P = 0.034 and 0.011, respectively). Ileal apparent digestibility for N of
      AA (P = 0.009) and most AA (P < 0.05), except for Met, Ile, Lys, Phe, and Ala,
      was decreased if measured at the ileum. However, correction for endogenous losses
      showed only Met digestibility did not differ between measurement sites.
      Differences between sites in excess of 15 percentage units were recorded for AA.
      Apparent and standardized ileal reactive Lys digestibility was 3.1 to 15.3
      percentage units greater than corresponding total tract digestibility values. For
      several indispensable AA, the bioavailability estimates currently used by the
      2006 NRC and the 2011 Association of American Feed Control Officials to derive
      allowance estimates for canine adult maintenance were greater than the
      digestibility values of these AA in the commercial dog foods evaluated. Although
      the canine large intestine is relatively short, the total tract digestibility
      assay in dogs can overestimate the digestibility of dietary AA and CP and may not
      be an accurate method for the measurement of absorption. In this study,
      bioavailability estimates of AA appeared to be less than those used to derive
      allowance estimates for commercial dog foods. Further work is required if current
      recommendations warrant adjustment. 

PMID- 23881685
TI  - Effects of a mixture of steam-flaked corn and extruded soybeans on performance,
      ruminal development, ruminal fermentation, and intestinal absorptive capability
      in veal calves.
AB  - This study investigated the effects of a mixture of steam-flaked corn and
      extruded soybeans on performance, ruminal development, ruminal fermentation
      variables, and intestinal absorptive capability in Holstein male calves (n = 39).
      Calves were assigned to 1 of 3 treatments (13 calves per treatment): 1) milk
      replacer (MR), 2) one-half of the amount of MR in treatment 1, plus a mixture of
      62.1% steam-flaked corn and 30.5% extruded soybeans provided ad libitum (HMCS),
      or 3) a mixture of 62.1% steam-flaked corn and 30.5% extruded soybeans provided
      ad libitum (CS). All the calves were started at 2 +/- 1 d of age and studied for
      150 d. Each 30 d was defined as 1 period. Dry matter intake and growth were
      measured daily and monthly, respectively. All calves were harvested at 150 d of
      age, after which rumen fluid was collected. Rumen and intestine samples were
      gathered. Calves fed MR exhibited greater BW (P = 0.001) and ADG (P < 0.001),
      compared with calves fed HMCS and CS from period 2 to 3; however, from period 4
      to 5, CS calves had greater (P < 0.04) ADG than MR calves. The treatments did not
      differ in final BW (P = 0.72) and ADG (P = 0.20) from period 2 to 5. Compared
      with HMCS and MR calves, CS calves had the greatest DMI (P < 0.001) and the least
      feed efficiency (P < 0.001) from period 2 to 5. For ruminal fermentation
      parameters, CS calves had decreased (P = 0.04) rumen pH than MR calves. The NH3
      concentrations were greater (P = 0.03) in calves fed HMCS than calves fed MR and
      CS. Total VFA concentrations were greatest in CS calves (P = 0.02). Calves fed CS
      had the greatest molar concentrations of propionate, butyrate, and valerate (P <
      0.002), and calves fed HMCS had the greatest molar concentrations of isobutyrate
      (P = 0.001) and isovalerate (P = 0.001). The CS calves exhibited greater empty
      rumen weight (P = 0.001), papillae length (P < 0.001), papillae width (P <
      0.001), rumen wall thickness (P = 0.012), and papillae density (P = 0.003). The
      greatest villus heights in the jejunum (P = 0.04) and ileum (P = 0.005) were
      observed in CS calves. Compared with HMCS calves, calves fed CS had greater
      villus:crypt ratios in the duodenum (P = 0.001) and jejunum (P = 0.001). Results
      indicate that CS improves ADG in period 4 to 5 and positively contributes to
      ruminal development, ruminal fermentation, and intestinal absorptive capability
      in veal calves. 

PMID- 23881686
TI  - Genetic parameters for the weights and yields of carcass cuts in Chianina cattle.
AB  - Chianina is the tallest and heaviest beef cattle breed in the world and 1 of the
      most appreciated breeds on the Italian meat market. A selection program focused
      on improving Chianina carcass quality could provide a further economic advantage
      to Chianina breeders. However, the current European carcass scoring system [i.e.,
      the SEUROP (S=superior, E=excellent, U= very good, R=good, O=fair, and P=poor)
      grid] is not suitable for use in selective breeding programs; methods based on
      carcass cuts would be much more efficient. Here, the genetic parameters of
      weights and yields (percentage of carcass weight) of the main commercial cuts
      were estimated on 842 Chianina carcasses (heifers and bullocks) using a mixed
      model that takes into account the fixed effects of herd, year of slaughter, and
      sex and the random additive effect of the animal; the carcass weight was also
      considered in cuts yield. The average carcass weights were 492.6 +/- 86.52 kg
      (males) and 312.1 +/- 68.74 kg (females), and the largest cut was the round, with
      a weight of 58.6 +/- 19.35 kg and yield of 24.4 +/- 1.28% in males and 40.2 +/-
      17.59 kg and 25.3 +/- 1.41% in females. The variability in cut weight was greater
      than that in yield percentage. The cut weight heritabilities ranged from 0.74
      (chuck) to 0.21 (short plate) whereas the yield heritabilities ranged from 0.88
      (loin) to 0.40 (brisket). The genetic correlations were generally high and
      positive between weights; correlation values with yields were lower and could be
      positive or negative. These findings suggest that a selection program to improve
      the carcass quality of Chianina beef using cuts data could potentially achieve
      good results.

PMID- 23881687
TI  - Association of SNP of neuropeptide Y, leptin, and IGF-1 genes with residual feed
      intake in confinement and under grazing condition in Angus cattle.
AB  - In this study we quantify and compare the phenotypic variation in residual feed
      intake (RFI) in 2 groups of Angus female calves: one carrying simultaneously
      putative favorable allelic variants (SNP) of neuropeptide Y, leptin, and IGF-1
      genes (VAL group) and another devoid of such alleles (CON group). We performed 2
      sequential trials: under confinement feeding a high-concentrate diet and under
      grazing condition. In confinement, 38 purebred Angus female calves [mean age and
      BW of 247 d (SD = 15) and 186 kg (SD = 33.2), respectively] were offered a total
      mixed ration diet (60:40 concentrate: alfalfa hay, as fed) ad libitum during 57
      d. Dry matter intake was estimated from the difference between offered and
      refused feed; BW was recorded every 2 wk. Under grazing, 12 heifers from each
      group were ranked by BW and RFI and randomly assigned to 4 pasture paddocks.
      Heifers were continuously stocked at high-quality, high-herbage-mass mixed
      pasture. Herbage DMI was determined using the n-alkane technique. Different
      models were used to determine RFI: models that use phenotypic data [RFI as
      described by Koch et al. (1963; RFIK) and RFI as described by ME (RFIME)] and
      models that use standards feeding data [RFI estimated by Fan et al. (1995; RFIF)
      and RFI in which the expected DMI was derived from equations in Standing
      Committee on Agriculture (1990; RFISCA)]. Least squares mean values (SE) of DMI
      (kg/d), metabolizable energy intake (MEI; Mcal/d), ADG (kg), RFIK (kg DM/d), and
      feed conversion ratio (FCR; kg DMI/kg ADG) for VAL and CON genotype groups were
      6.65 and 6.89 (0.49), 16.7 and 17.4 (1.44), 1.24 and 1.24 (0.03), -0.11 and 0.11
      (0.09), and 5.8 and 5.8 (0.14), respectively, in the confinement trial. In the
      grazing trial least squares mean values (SE) of herbage DMI (kg/d), ADG (kg), MEI
      (Mcal/d), RFIK, and FCR of VAL and CON groups were 8.76 and 10.93 (0.71), 1.4 and
      1.37 (0.05), 25.5 and 31.7 (2.09), -1.02 and 1.02 (0.42), and 6.41 and 6.96
      (0.46), respectively. Genotyped groups tended to differ in DMI (P = 0.10), in MEI
      (P = 0.06), and in RFIK (P = 0.10), differed in RFIF (P = 0.010), and did not
      differ in ADG or FCR during confinement. During grazing, genotyped groups
      differed in DMI (P = 0.005), in MEI (P = 0.006), and in RFIK (P = 0.002) but did
      not differ in ADG and FCR. Our results demonstrate a strong association between
      these 3 SNP and RFI when animals were grazing on a high-quality, high
      availability pasture, whereas a weak effect was observed under confinement.

PMID- 23881688
TI  - Estimates of genetic parameters for stayability to consecutive calvings of
      Canadian Simmentals by random regression models.
AB  - Stayability to consecutive calvings was selected as a measure of cow longevity in
      the Canadian Simmental population. Calving performance data on 188,579 cows and
      culling information from the Total Herd Reporting System were used to determine
      whether a cow stayed in a herd for her second and later (up to the eighth)
      calvings, given that she had calved as 2 yr old. Binary records (n = 1,164,319)
      were analyzed with animal linear and threshold models including fixed effects of
      year of birth by season of birth by parity number and age of cow at first calving
      by parity number and random effects of contemporary group (CG) defined as herd of
      birth within year by season, animal additive genetic effect, and a cow permanent
      environmental (PE) effect. All random effects were Legendre polynomial
      regressions of the same order, defined on the scale from second to the eighth
      calving. Bayesian methods with Gibbs sampling were used to estimate covariance
      components and genetic parameters for random effects of models and selected
      variables on the longitudinal scale. Bayes factors and analyses of mean squared
      error and correlation between observed and predicted observations indicated that
      the linear model with regressions of order 3 was most plausible for generating
      the current data compared with a fixed regression and other random regression
      (both linear and threshold) models of order up to 4. Estimates of variances for
      all random effects from the best fitting model changed with the calving number.
      Estimates of heritability decreased in time: from 0.35 (SD = 0.006) for
      stayability to second calving to 0.13 (SD = 0.004) for stayability to the eighth
      calving. Variance due to PE effect constituted the largest part of the total
      variance of stayability for all longitudinal points followed by genetic and CG
      components. Genetic effects of stayability to different calvings were relatively
      highly correlated, from 0.62 (SD = 0.011) to 0.99 (SD = 0.001), and correlation
      decreased with the time span between calvings. Correlations for PE and CG effects
      showed similar trends. Animal genetic effect seemed to be less variable on the
      longitudinal scale compared with other random effects of the model. The first 2
      principal components explained from 95% (PE effects) to 99% (genetic effect) of
      the total variance. The overall level of genetic stayability curve correlated
      well (from 0.87 to 0.99, with SD < 0.006) with genetic stayability to different
      calvings and therefore could be used as a single criterion in selection for
      stayability. 

PMID- 23881689
TI  - HMGA2 expression in white adipose tissue linking cellular senescence with
      diabetes.
AB  - There is a clear link between overweight, gain of white adipose tissue, and
      diabetes type 2 (T2D). The molecular mechanism of the gain of adipose tissue is
      linked with the expression of high mobility group protein AT-hook 2 (HMGA2), and
      recent studies revealed an association with a SNP near HMGA2. In this study, we
      investigated the gene expression of HMGA2, p14 (Arf) , CDKN1A, and BAX in human
      abdominal subcutaneous white adipose tissue from 157 patients. We found a
      significant higher HMGA2 expression in obese individuals than in non-obese
      patients. Furthermore, the HMGA2 expression in white adipose tissue in patient
      with type 2 diabetes was significantly higher than in nondiabetic patients. There
      is an association between the DNA-binding nonhistone protein HMGA2 and the risk
      of developing T2D that remains mechanistically unexplained so far. Likewise,
      p14(Arf), an inducer of cellular senescence, has been associated with the
      occurrence of T2D. The data of the present study provide evidence that both
      proteins act within the same network to drive proliferation of adipose tissue
      stem and precursor cells, senescence, and increased risk of T2D, respectively. 

PMID- 23881691
TI  - Multiple photoluminescence from 1,2-dinaphthyl-ortho-carborane.

PMID- 23881690
TI  - Determinants of health and disability in ageing population: the COURAGE in Europe
      Project (collaborative research on ageing in Europe).
AB  - COURAGE in Europe was a 3-year project involving 12 partners from four European
      countries and the World Health Organization. It was inspired by the pressing need
      to integrate international studies on disability and ageing in light of an
      innovative perspective based on a validated data-collection protocol. COURAGE in
      Europe Project collected data on the determinants of health and disability in an
      ageing population, with specific tools for the evaluation of the role of the
      built environment and social networks on health, disability, quality of life and
      well-being. The main survey was conducted by partners in Finland, Poland and
      Spain where the survey has been administered to a sample of 10,800 persons, which
      was completed in March 2012. The newly developed and validated COURAGE Protocol
      for Ageing Studies has proven to be a valid tool for collecting comparable data
      in ageing population, and the COURAGE in Europe Project has created valid and
      reliable scientific evidence, demonstrating cross-country comparability, for
      disability and ageing research and policy development. It is therefore
      recommended that future studies exploring determinants of health and disability
      in ageing use the COURAGE-derived methodology. KEY PRACTITIONER MESSAGE: COURAGE
      in Europe Project collected data on the determinants of health and disability in
      an ageing population, with specific tools for the evaluation of the role of built
      environment and social networks on health, disability quality of life and well
      being. The COURAGE Protocol for Ageing Studies has proven to be a valid tool for
      collecting comparable data in the ageing population. The COURAGE in Europe
      Consortium recommends that future studies exploring determinants of health and
      disability in ageing use COURAGE-derived methodology.

PMID- 23881693
TI  - Chemical mechanisms of the toxicological properties of nanomaterials: generation
      of intracellular reactive oxygen species.
AB  - As more and more nanomaterials with novel physicochemical properties or new
      functions are created and used in different research fields and industrial
      sectors, the scientific and public concerns about their toxic effects on human
      health and the environment are also growing quickly. In the past decade, the
      study of the toxicological properties of nanomaterials/nanoparticles has formed a
      new research field: nanotoxicology. However, most of the data published relate to
      toxicological phenomena and there is less understanding of the underlying
      mechanism for nanomaterial-induced toxicity. Nanomaterial-induced reactive oxygen
      species (ROS) play a key role in cellular and tissue toxicity. Herein, we
      classify the pathways for intracellular ROS production by nanomaterials into 1)
      the direct generation of ROS through nanomaterial-catalyzed free-radical
      reactions in cells, and 2) the indirect generation of ROS through disturbing the
      inherent biochemical equilibria in cells. We also discuss the chemical mechanisms
      associated with above pathways of intracellular ROS generation, from the
      viewpoint of the high reactivity of atoms on the nanosurface. We hope to aid in
      the understanding of the chemical origin of nanotoxicity to provide new insights
      for chemical and material scientists for the rational design and creation of
      safer and greener nanomaterials.

PMID- 23881694
TI  - High-content screening: imaging, analysis, and applications.

PMID- 23881695
TI  - Topical application of tranexamic acid for the reduction of bleeding.
AB  - BACKGROUND: Intravenous tranexamic acid reduces bleeding in surgery, however, its
      effect on the risk of thromboembolic events is uncertain and an increased risk
      remains a theoretical concern. Because there is less systemic absorption
      following topical administration, the direct application of tranexamic acid to
      the bleeding surface has the potential to reduce bleeding with minimal systemic
      effects. OBJECTIVES: To assess the effects of the topical administration of
      tranexamic acid in the control of bleeding. SEARCH METHODS: We searched the
      Cochrane Injuries Group Specialised Register; Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library; Ovid MEDLINE(r), Ovid
      MEDLINE(r) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(r) Daily and
      Ovid OLDMEDLINE(r); Embase Classic + Embase (OvidSP); PubMed and ISI Web of
      Science (including Science Citation Index Expanded and Social Science Citation
      Index (SCI-EXPANDED & CPCI-S)). We also searched online trials registers to
      identify ongoing or unpublished trials. The search was run on the 31st May 2013.
      SELECTION CRITERIA: Randomised controlled trials comparing topical tranexamic
      acid with no topical tranexamic acid or placebo in bleeding patients. DATA
      COLLECTION AND ANALYSIS: Two authors examined the titles and abstracts of
      citations from the electronic databases for eligibility. Two authors extracted
      the data and assessed the risk of bias for each trial. Outcome measures of
      interest were blood loss, mortality, thromboembolic events (myocardial
      infarction, stroke, deep vein thrombosis and pulmonary embolism) and receipt of a
      blood transfusion. MAIN RESULTS: We included 29 trials involving 2612
      participants. Twenty-eight trials involved patients undergoing surgery and one
      trial involved patients with epistaxis (nosebleed). Tranexamic acid (TXA) reduced
      blood loss by 29% (pooled ratio 0.71, 95% confidence interval (CI) 0.69 to 0.72;
      P < 0.0001). There was uncertainty regarding the effect on death (risk ratio (RR)
      0.28, 95% CI 0.06 to 1.34; P = 0.11), myocardial infarction (RR 0.33, 95% CI 0.04
      to 3.08; P = 0.33), stroke (RR 0.33, 95% CI 0.01 to 7.96; P = 0.49), deep vein
      thrombosis (RR 0.69, 95% CI 0.31 to 1.57; P = 0.38) and pulmonary embolism (RR
      0.52, 95% CI 0.09 to 3.15; P = 0.48). TXA reduced the risk of receiving a blood
      transfusion by a relative 45% (RR 0.55, 95% CI 0.55 to 0.46; P < 0.0001). There
      was substantial statistical heterogeneity between trials for the blood loss and
      blood transfusion outcomes. AUTHORS' CONCLUSIONS: There is reliable evidence that
      topical application of tranexamic acid reduces bleeding and blood transfusion in
      surgical patients, however the effect on the risk of thromboembolic events is
      uncertain. The effects of topical tranexamic acid in patients with bleeding from
      non-surgical causes has yet to be reliably assessed. Further high-quality trials
      are warranted to resolve these uncertainties before topical tranexamic acid can
      be recommended for routine use.

PMID- 23881696
TI  - Synthesis and biological evaluation of a series of dithiocarbamates as new
      cholinesterase inhibitors.
AB  - In the present paper, a novel series of dithiocarbamates was synthesized via the
      treatment of 4-(trifluoromethyl)benzyl chloride with appropriate sodium salts of
      N,N-disubstituted dithiocarbamic acids. The chemical structures of the compounds
      were elucidated by (1) H NMR, mass spectral data, and elemental analyses. Each
      derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE)
      and butyrylcholinesterase (BuChE) using a modification of Ellman's
      spectrophotometric method. The most potent AChE inhibitor was found as compound
      2g (IC50  = 0.53 +/- 0.001 uM) followed by compounds 2f (IC50  = 0.74 +/- 0.001
      uM) and 2j (IC50  = 0.89 +/- 0.002 uM) when compared with donepezil (IC50  =
      0.048 +/- 0.001 uM). Compounds 2f and 2g were more effective than donepezil (IC50
      = 7.88 +/- 0.52 uM) on BuChE inhibition. Compounds 2f and 2g exhibited the
      inhibitory effect on BuChE with IC50 values of 1.39 +/- 0.041 and 3.64 +/- 0.072
      uM, respectively. 

PMID- 23881697
TI  - Risk of heart failure associated with dopamine agonists: a nested case-control
      study.
AB  - BACKGROUND: Recent evidence has emerged that a dopamine agonist, pramipexole, may
      increase the risk of heart failure among Caucasian patients, but the association
      has not been examined among Asian patients. The aim of this study was to explore
      the relationship between use of dopamine agonists and the risk of heart failure.
      METHODS: Using data from Taiwan's National Health Insurance research database
      (NHIRD), we identified a population-based cohort comprising 27,135 patients who
      were prescribed anti-parkinsonian drugs between 2001 and 2010. We conducted a
      nested case-control study in which 1,707 cases of newly diagnosed heart failure
      were matched to 3,414 controls (1:2 matched according to age, gender and cohort
      entry year) within this cohort. Multivariable conditional logistic regressions
      were used to estimate the association between use of dopamine agonists and heart
      failure. RESULTS: An increased risk of heart failure was observed with current
      use of ergot-derived dopamine agonists (adjusted odds ratio [OR] 1.46, 95 %
      confidence interval [CI] 1.00-2.12) but not with current use of non-ergot-derived
      dopamine agonists (adjusted OR 1.24, 95 % CI 0.84-1.82). Among non-ergot-derived
      dopamine agonists, both pramipexole (adjusted OR 1.40, 95 % CI 0.75-2.61) and
      ropinirole (adjusted OR 1.22, 95 % CI 0.76-1.95) showed a non-significantly
      increased heart failure risk. Although the findings of our study were limited by
      lack of statistical power, a clear pattern of an increased duration of
      pramipexole use and an increased risk of heart failure were observed. CONCLUSION:
      Use of dopamine agonists, including pramipexole, was associated with non
      significantly increased risks of heart failure in this population-based study in
      Taiwan. Further investigation is needed to clarify this potential association.

PMID- 23881698
TI  - Prevalence and determinants of anticholinergic medication use in elderly dementia
      patients.
AB  - BACKGROUND: People with dementia are sensitive to cognitive side effects of
      anticholinergic drugs. However, little is known about the prevalence of
      anticholinergic medications and its predictors in a nationally representative
      sample of community-based elderly dementia patients in the USA. OBJECTIVES: The
      objectives of the study were to determine the prevalence and predictors of
      anticholinergic drugs use in elderly dementia patients. METHODS: The study
      involved retrospective analysis of the 2005-2009 Medical Expenditure Panel
      Surveys (MEPS), a nationally representative sample of the non-institutionalized
      US population. The study evaluated annual prevalence of anticholinergic drug use
      during the study period and factors associated with the use of anticholinergics
      among community-dwelling persons aged 65 and older with dementia. The
      anticholinergic drugs were identified using the Anticholinergic Drug Scale (ADS).
      Multiple logistic regression within the conceptual framework of the Anderson
      Behavioral Model was performed to identify predictors associated with clinically
      significant anticholinergic drug (ADS level 2 or 3) use. RESULTS: According to
      the MEPS, there were a total of 1.56 [95 % confidence interval (CI) 1.34, 1.73]
      million elderly dementia patients annually during the study period.
      Approximately, 23.3 % (95 % CI 19.2, 27.5) of elderly dementia patients used
      clinically significant anticholinergic agents (ADS level 2 or 3). Among the need
      factors, elderly dementia patients having mood disorders [odds ratio (OR) 2.19;
      95 % CI 1.19, 4.06] and urinary incontinence (OR 6.58; 95 % CI 2.84, 15.29) were
      more likely to use drugs with clinically significant anticholinergic activities.
      Of the enabling factors, the odds of receiving higher-level anticholinergic drugs
      were significantly lower for patients who resided in the West region (OR 0.41; 95
      % CI 0.17, 0.95) compared to the reference group, Northeast. CONCLUSION: Over one
      in five elderly dementia patients used drugs with clinically significant
      anticholinergic effects. Mood disorder, urinary incontinence, and region were
      significantly associated with use of these drugs. Concerted efforts are needed to
      improve the quality of medication use by focusing on clinically significant
      anticholinergic agents.

PMID- 23881699
TI  - Validity of inorganic nanosheets as an efficient planar substituent to enhance
      the enantioselectivity of transition-metal-catalyzed asymmetric synthesis.
AB  - Effectively enhancing the enantioselectivity is a persistent challenge in
      heterogeneous asymmetric catalysis. Here, the validity of a layered double
      hydroxides (LDH) nanosheet as an efficient planar substituent to enhance the
      enantioselectivity has been investigated theoretically; first in vanadium
      catalyzed asymmetric epoxidation of allylic alcohols, and then in zinc-catalyzed
      direct asymmetric aldol addition. The computational predication is further
      confirmed experimentally in zinc-catalyzed direct asymmetric aldol addition by
      controlling the location of catalytic sites. 

PMID- 23881700
TI  - The role of microRNAs in tumors.
AB  - The cancers are a series of serious diseases in the world, and the mechanism
      involved in many cancers has not yet been fully elucidated. Therefore, it is a
      very major and significant to explore the molecular mechanisms of cancer
      occurence and development. MicroRNAs (miRNAs), a class of molecules that
      regulates gene at post-transcription expression, play an important role in
      tumorigenesis. It has been proved that a number of miRNAs identified as
      aberrantly expressed during cancer development. In addition, some of the miRNAs
      may have prognostic significance. It is the aim of this review to describe the
      important role of miRNAs in cancer initiation and development as predictive,
      diagnostic, prognostic biomarkers and novel therapeutic strategies.

PMID- 23881701
TI  - Novel arylhydrazone derivatives bearing a rhodanine moiety: synthesis and
      evaluation of their antibacterial activities.
AB  - A series of arylhydrazone derivatives bearing a rhodanine moiety have been
      synthesized, characterized, and evaluated as antibacterial agents. Some of these
      compounds showed potent antibacterial activities against several different
      strains of Gram-positive bacteria, including multidrug-resistant clinical
      isolates. Of the compounds tested, IIk and IIIk were identified as the most
      effective, with minimum inhibitory concentration values of 2-4 MUg/mL against
      multidrug-resistant Gram-positive organisms, including methicillin-resistant and
      quinolone-resistant Staphylococcus aureus. None of the compounds exhibited any
      activity against the Gram-negative bacteria Escherichia coli 1356 at 64 MUg/mL.

PMID- 23881702
TI  - Isoalantolactone, a sesquiterpene lactone, induces apoptosis in SGC-7901 cells
      via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways.
AB  - Isoalantolactone, a sesquiterpene lactone, possesses anti-fungal as well as
      cytotoxic properties. In this study, the effects of Isoalantolactone on cell
      viability, cell cycle, and apoptosis were investigated in human gastric
      adenocarcinoma SGC-7901 cells. The results demonstrated that Isoalantolactone
      induced morphological changes and decreased cell viability. Subsequently, we
      found that Isoalantolactone induced G2/M and S phase arrest, which was associated
      with a decrease in the expression level of cyclin B1. Apoptosis triggered by
      Isoalantolactone was visualized using propidium iodide (PI) and Annexin V-FITC/PI
      staining. Isoalantolactone-induced apoptosis of SGC-7901 cells was associated
      with the dissipation of mitochondrial membrane potential (DeltaPsi m) that was
      due to the down-regulation of Bcl-2 and up-regulation of Bax that led to the
      cleavage of caspase-3. Additionally, it was found that Isoalantolactone was
      involved in the inhibition of phosphorylation of PI3K/Akt. Isoalantolactone
      induced cytotoxicity and apoptosis of SGC-7901 cells involve mitochondria-caspase
      and PI3K/Akt dependent pathways, which gives the rationale for in vivo studies on
      the utilization of Isoalantolactone as a potential cancer therapeutic compound.

PMID- 23881703
TI  - Cytotoxic lignans from Viburnum foetidum.
AB  - Two new lignans, 3,4,4'-trihydroxy-3',9-dimethoxy-9,9'-epoxylignan (1), 3,4'
      dihydroxy-3',4, 9-trimethoxy-9,9'-epoxylignan (2), together with one known
      compound, 4,4'-dihydroxy-3,3',9-trimethoxy-9,9'-epoxylignan (3), were isolated
      from the 95 % EtOH extract of Viburnum foetidum. The structures of the two new
      compounds were elucidated on the basis of 1D, 2D-NMR, and mass spectral analysis.
      All the lignans were in vitro evaluated for their cytotoxic activities against
      four tumor cell lines (A549, SK-OV-3, SKMEL-2 and HCT15).

PMID- 23881704
TI  - A commentary on iPS cells: potential applications in autologous transplantation,
      study of illnesses and drug screening.
AB  - Undoubtedly, the focus of the field of stem cell research is predominantly aimed
      at the artificial reprogramming of human somatic cells for the production of
      induced pluripotent stem (iPS) cells. This relatively new technology may
      circumvent the ethical issues of using human embryonic stem (hES) cells for the
      potential applications in cell replacement therapy. Besides such ethical issues,
      iPS cell technology offers the advantage of obtaining patient-derived tissues
      and/or cells, which may be utilized for autologous transplantation and tissue
      regeneration, investigation of a variety of human illnesses and for the screening
      of new drugs. The field of stem cell research has placed a major emphasis in
      understanding the genetic and epigenetic codes for pluripotency, in order to
      control and optimize autologous transplantation techniques and avoid teratoma
      formation.

PMID- 23881705
TI  - Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      with selective loss of upper and lower motor neurons. At sites of motor neuron
      injury, neuroinflammation is a prominent pathological finding and is
      characterized by microglial activation, astrogliosis, and infiltration of
      monocytes and T-cells. Both innate and adaptive immune responses actively
      influence disease progression in animal models and in ALS patients, and promote
      neuroprotection or neurotoxicity at different stages of disease. The early immune
      reaction to signals from injured motor neurons is to rescue and repair damaged
      tissue. As disease accelerates, a shift occurs from beneficial immune responses
      (involving M2 microglia and regulatory T-cells) to deleterious immune responses
      (involving M1 microglia and Th1 cells). In this review, we underscore the
      importance of immune-mediated mechanisms in the pathogenesis of ALS and discuss
      the alterations and distinct phenotypes of immune cells at the different stages
      of disease. The better we understand the dynamic changes that occur within the
      immune system over the course of disease, the better we will be able to develop
      effective therapeutic regimens in ALS. 

PMID- 23881707
TI  - Problems with paraphilias in the DSM-5.
AB  - This paper critiques changes in the diagnositic criteria for the paraphilias as
      set out in the DSM-5. In addition to general areas of concern, five specific
      problem areas are identified. This includes: definitions by exclusion; culturally
      based criteria; ignoring etiology; minimizing consent issues; and lack of field
      trials. A suggestion to improve the diagnostic criteria is offered. 

PMID- 23881706
TI  - Microglial phenotype and adaptation.
AB  - Microglia are the prime innate immune cells of the central nervous system. They
      can transit from a (so-called) resting state under homeostatic conditions towards
      a pro-inflammatory activation state upon homeostatic disturbances. Under
      neurodegenerative conditions, microglia have been largely perceived as neurotoxic
      cells. It is now becoming clear that resting microglia are not inactive but that
      they serve house-keeping functions. Moreover, microglia activity is not limited
      to proinflammatory responses, but covers a spectrum of reactive profiles.
      Depending on the actual situation, activated microglia display specific effector
      functions supporting inflammation, tissue remodeling, synaptic plasticity and
      neurogenesis. Many of these functions not only relate to the current state of the
      local neural environment but also depend on previous experience. In this review,
      we address microglia functions with respect to determining factors, phenotypic
      presentations, adaptation to environmental signals and aging. Finally, we point
      out primary mechanisms of microglia activation, which may comprise therapeutic
      targets to control neuro-inflammatory and neurodegenerative activity. 

PMID- 23881708
TI  - Activated depression: mixed bipolar disorder or agitated unipolar depression?
AB  - The combination of depression and activation presents clinical and diagnostic
      challenges. It can occur, in either bipolar disorder or major depressive
      disorder, as increased agitation as a dimension of depression. What is called
      agitation can consist of expressions of painful inner tension or as disinhibited
      goal-directed behavior and thought. In bipolar disorder, elements of depression
      can be combined with those of mania. In this case, the agitation, in addition to
      increased motor activity and painful inner tension, must include symptoms of
      mania that are related to goal-directed behavior or manic cognition. These
      diagnostic considerations are important, as activated depression potentially
      carries increased behavioral risk, especially for suicidal behavior, and optimal
      treatments for depressive episodes differ between bipolar disorder and major
      depressive disorder. 

PMID- 23881709
TI  - Knowledge and attitudes about attention-deficit/hyperactivity disorder (ADHD) and
      its treatment: the views of children, adolescents, parents, teachers and
      healthcare professionals.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common neuro-developmental
      disorder that causes controversy; this may have a negative effect on the ability
      of families, teachers and healthcare professionals to achieve shared
      understanding and goals. This article reviews recent research of the knowledge
      and attitudes of children, adolescents, parents, teachers, healthcare
      professionals and the public about ADHD. Findings suggest that misconceptions
      about ADHD persist, and children with ADHD and their parents report stigmatizing
      experiences. Educational interventions to improve the knowledge of teachers about
      ADHD appeared to be effective in the short term. Parents and professionals
      working together in the diagnosis and treatment of children with ADHD may have
      different views about their roles in the shared decision-making process. Studies
      have reported both similarities and differences in parents' and professionals'
      views about the effectiveness of treatments for ADHD, but all stakeholders
      supported the principles of information-sharing and working in partnership. 

PMID- 23881711
TI  - Capacity, confidentiality and consequences: balancing responsible medical care
      with mental health law.

PMID- 23881710
TI  - Assessing the roles of stimulants/stimulant-like drugs and dopamine-agonists in
      the treatment of bipolar depression.
AB  - Bipolar depression is considered the most difficult-to-treat phase of bipolar
      disorder, in relation to its pervasiveness and efficacy and/or tolerability
      limitations of available treatments. Indeed, most mood stabilizers and atypical
      antipsychotics are not as effective in ameliorating depressive compared with
      manic symptoms, and entail substantial tolerability limitations. However, the use
      of antidepressants is highly controversial, as their efficacy appears less robust
      in bipolar compared with unipolar depression. In addition, antidepressants, in
      spite of generally having adequate somatic tolerability, in BD may be associated
      with a higher risk of manic/hypomanic switch, suicidality and rapid cycling.
      Among alternative pharmacological strategies, compounds with stimulant and pro
      dopaminergic effects, such as methylphenidate, modafinil, armodafinil and
      pramipexole, have showed potential antidepressant activity, even though their use
      in clinical practice has been limited by the paucity of controlled evidence. This
      article seeks to review available evidence about the use of the aforementioned
      compounds in the treatment of bipolar depression. Findings from reviewed studies
      suggested that pro-dopaminergic compounds, such as pramipexole and
      stimulants/stimulant-like agents, deserve consideration as adjunctive therapies
      in bipolar depressed patients, at least in some subgroups of patients.
      Nevertheless, caution regarding their use is recommended as further clinical
      trials with larger samples and longer follow-up periods are necessary to clarify
      the roles of these medications in bipolar depression. 

PMID- 23881712
TI  - Pediatric depression: an evidence-based update on treatment interventions.
AB  - Depression is a common condition among children and adolescents, with lasting
      detrimental effects on health, and social and occupational functioning. Despite
      being well-positioned to treat depression, primary care providers (PCPs) cite
      significant barriers. This review aims to summarize recent evidence to provide
      practical guidance to PCPs on the management of pediatric depression in their
      practices. Following identification and assessment, PCPs should provide general
      initial management. Children and adolescents with mild depression can be managed
      with active support and symptom monitoring, while those with moderate-to-severe
      depression can be treated with psychotherapy and/or antidepressants, which may
      involve referral to mental health specialty care. Less is known about the
      treatment of depression in children under the age of 12 years, who may be
      candidates for earlier referral to mental health specialty care. PCPs have the
      potential to improve the recognition and management of depression in young
      people, having lasting individual and societal benefits.

PMID- 23881713
TI  - Pharmacoepidemiology of antipsychotic use in youth with ADHD: trends and clinical
      implications.
AB  - Although concern has been raised about antipsychotic prescribing to youth with
      attention-deficit/hyperactivity disorder (ADHD), the available database is
      limited to individual studies. Therefore, in order to provide a synthesis of
      prevalence and time trends, we conducted a systematic review and pooled analysis
      of pharmaco-epidemiologic data on antipsychotic use in ADHD youth. Of 1806 hits,
      21 studies (N) were retained that reported analyzable data for three separate
      populations: 1) antipsychotic-treated youth (N = 15, n = 341,586); 2) ADHD youth
      (N = 9, n = 6,192,368), and 3) general population youth (N = 5, n = 14,284,916).
      Altogether, 30.5 +/- 18.5% of antipsychotic-treated youth had ADHD. In
      longitudinal studies, this percentage increased over time (1998-2007) from 21.7
      +/- 7.1% to 27.7 +/- 7.7%, ratio = 1.3 +/- 0.4. Furthermore, 11.5 +/- 17.5% of
      ADHD youth received antipsychotics. In longitudinal studies, this percentage also
      increased (1998-2006) from 5.5 +/- 2.6% to 11.4 +/- 6.7%, ratio = 2.1 +/- 0.6.
      Finally, 0.12 +/- 0.07% of youth in the general population were diagnosed with
      ADHD and received antipsychotics. Again, in longitudinal studies, this percentage
      increased over time (1993-2007): 0.13 +/- 0.09% to 0.44 +/- 0.49%, ratio = 3.1 +/
      2.2. Taken together, these data indicate that antipsychotics are used by a
      clinically relevant and increasing number of youth with ADHD. Reasons for and
      risk/benefit ratios of this practice with little evidence base require further
      investigation.

PMID- 23881715
TI  - A porphyrin skeleton containing a palladacyclopentadiene.

PMID- 23881716
TI  - Synthesis and absolute configuration of demethyl (C-11) cezomycin.
AB  - The synthesis of (-)-demethyl (C-11) cezomycin was achieved through an efficient
      route that features the use of a Kulinkovich reaction to couple two
      multifunctionality-containing fragments and a cascade of ring opening of
      cyclopropanol/1,5-hydrogen shift/desilylation-oxidation. The hidden yet
      undeniable problem of irreproducible specific rotation for this family of
      compounds was solved by sufficient acidification. The absolute configuration for
      the natural product was thus established as the mirror image of the synthetic
      sample. 

PMID- 23881714
TI  - Mental health collaborative care and its role in primary care settings.
AB  - Collaborative care models (CCMs) provide a pragmatic strategy to deliver
      integrated mental health and medical care for persons with mental health
      conditions served in primary care settings. CCMs are team-based intervention to
      enact system-level redesign by improving patient care through organizational
      leadership support, provider decision support, and clinical information systems,
      as well as engaging patients in their care through self-management support and
      linkages to community resources. The model is also a cost-efficient strategy for
      primary care practices to improve outcomes for a range of mental health
      conditions across populations and settings. CCMs can help achieve integrated care
      aims underhealth care reform yet organizational and financial issues may affect
      adoption into routine primary care. Notably, successful implementation of CCMs in
      routine care will require alignment of financial incentives to support systems
      redesign investments, reimbursements for mental health providers, and adaptation
      across different practice settings and infrastructure to offer all CCM
      components. 

PMID- 23881717
TI  - Demographic consequences of chromatic leaf defence in tropical tree communities:
      do red young leaves increase growth and survival?
AB  - BACKGROUND: Many tropical forest tree species delay greening their leaves until
      full expansion. This strategy is thought to provide newly flushing leaves with
      protection against damage by herbivores by keeping young leaves devoid of
      nutritive value. Because young leaves suffer the greatest predation from
      invertebrate herbivores, delayed greening could prevent costly tissue loss. Many
      species that delay greening also produce anthocyanin pigments in their new
      leaves, giving them a reddish tint. These anthocyanins may be fungicidal, protect
      leaves against UV damage or make leaves cryptic to herbivores blind to the red
      part of the spectrum. METHODS: A comprehensive survey was undertaken of
      seedlings, saplings and mature trees in two diverse tropical forests: a rain
      forest in western Amazonia (Yasuni National Park, Ecuador) and a deciduous forest
      in Central America (Barro Colorado Island, Panama). A test was made of whether
      individuals and species with delayed greening or red-coloured young leaves showed
      lower mortality or higher relative growth rates than species that did not. KEY
      RESULTS: At both Yasuni and Barro Colorado Island, species with delayed greening
      or red young leaves comprised significant proportions of the seedling and tree
      communities. At both sites, significantly lower mortality was found in seedlings
      and trees with delayed greening and red-coloured young leaves. While there was
      little effect of leaf colour on the production of new leaves of seedlings,
      diameter relative growth rates of small trees were lower in species with delayed
      greening and red-coloured young leaves than in species with regular green leaves,
      and this effect remained when the trade-off between mortality and growth was
      accounted for. CONCLUSIONS: Herbivores exert strong selection pressure on
      seedlings for the expression of defence traits. A delayed greening or red
      coloured young leaf strategy in seedlings appears to be associated with higher
      survival for a given growth rate, and may thus influence the species composition
      of later life stages.

PMID- 23881718
TI  - PAP/HIP protein is an obesogenic factor.
AB  - In this article we report the obesogenic role of the acute phase protein PAP/HIP.
      We found that the transgenic TgPAP/HIP mice develop spontaneous obesity under
      standard nutritional conditions, with high levels of glucose, leptin, and LDL and
      low levels of triglycerides and HDL in blood. Accordingly, PAP/HIP-deficient mice
      are skinny under standard nutritional conditions. We also found that expression
      of PAP/HIP is induced in intestinal epithelial cells in response to gavage with
      olive oil and this induction is AG490 sensitive. We demonstrated that incubation
      of 3T3-L1 preadipocytes with a low concentration as 1 ng/ml of recombinant
      PAP/HIP results in accelerated BrdU incorporation in vitro. PAP/HIP-dependent
      adipocytes growth is sensitive to the MEK inhibitor U0126. Finally, patients with
      severe obesity present higher blood levels of PAP/HIP than non-obese control
      individuals. Altogether our data suggest that PAP/HIP could be a mediator of fat
      tissue development, released by the intestine and induced by the presence of food
      into the gut.

PMID- 23881719
TI  - Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential
      role of D-serine.
AB  - Trigeminal neuropathic pain affects millions of people worldwide. Despite decades
      of study on the neuronal processing of pain, mechanisms underlying enhanced pain
      states after injury remain unclear. N-methyl-D-aspartate (NMDA) receptor
      dependent changes play a critical role in triggering central sensitization in
      neuropathic pain. These receptors are regulated at the glycine site through a
      mandatory endogenous co-agonist D-serine, which is synthesized by astrocytes.
      Therefore, the present study was carried out to determine whether astrocytes are
      involved, through D-serine secretion, in dynamic mechanical allodynia (DMA)
      obtained after chronic constriction of the infraorbital nerve (CCI-IoN) in rats.
      Two weeks after CCI-IoN, an important reaction of astrocytes was present in the
      medullary dorsal horn (MDH), as revealed by an up-regulation of glial fibrillary
      acidic protein (GFAP) in allodynic rats. In parallel, an increase in D-serine
      synthesis, which co-localized with its synthesis enzyme serine racemase, was
      strictly observed in astrocytes. Blocking astrocyte metabolism by intracisternal
      delivery of fluorocitrate alleviated DMA. Furthermore, the administration of D
      amino-acid oxidase (DAAO), a D-serine-degrading enzyme, or that of L-serine O
      sulfate (LSOS), a serine racemase inhibitor, significantly decreased pain
      behavior in allodynic rats. These results demonstrate that astrocytes are
      involved in the modulation of orofacial post-traumatic neuropathic pain via the
      release of the gliotransmitter D-serine.

PMID- 23881720
TI  - A single-parameter logistic equation for fitting concentration-response curves
      from standard acute ecotoxicity assays.
AB  - A set of 69 concentration-response curves from 5 acute ecotoxicity assays was
      fitted with a 2-parameter logistic equation. High correlation between values of
      regression parameters suggested similar slopes of the curves. This enabled
      derivation of the empirical single-parameter logistic equation with the sole
      median effective concentration (EC50) parameter. Such an equation might be useful
      in the evaluation of lower-quality (preliminary) experimental data and for the
      reduction of the number of test organisms and of testing costs.

PMID- 23881721
TI  - Characterising neovascularisation in fracture healing with laser Doppler and
      micro-CT scanning.
AB  - Vascularity of the soft tissues around a bone fracture is critical for successful
      healing, particularly when the vessels in the medullary canal are ruptured. The
      objective of this work was to use laser Doppler and micro-computer tomography
      (micro-CT) scanning to characterise neovascularisation of the soft tissues
      surrounding the fracture during healing. Thirty-two Sprague-Dawley rats underwent
      mid-shaft osteotomy of the left femur, stabilised with a custom-designed external
      fixator. Five animals were killed at each of 2, 4 days, 1, 2, 4 and 6 weeks post
      operatively. Femoral blood perfusion in the fractured and intact contralateral
      limbs was measured using laser Doppler scanning pre- and post-operatively and
      throughout the healing period. At sacrifice, the common iliac artery was
      cannulated and infused with silicone contrast agent. Micro-CT scans of the femur
      and adjacent soft tissues revealed vessel characteristics and distribution in
      relation to the fracture zone. Blood perfusion dropped immediately after surgery
      and then recovered to greater than the pre-operative level by proliferation of
      small vessels around the fracture zone. Multi-modal imaging allowed both
      longitudinal functional and detailed structural analysis of the
      neovascularisation process. 

PMID- 23881722
TI  - Use of pertuzumab for the treatment of HER2-positive metastatic breast cancer.
AB  - INTRODUCTION: Targeting the human epidermal growth factor receptor (HER) family
      of tyrosine kinase receptors has proven to be effective as a therapeutic strategy
      for HER type 2 (HER2)-positive breast cancer. Since resistance to trastuzumab
      occurs relatively frequently, particularly in the metastatic setting, novel anti
      HER2 targeted therapies with complementary and/or synergistic mechanisms of
      action have been under development. Pertuzumab, a HER2-targeted monoclonal
      antibody that prevents HER2 dimerisation, is the first of a class of promising
      targeted agents for the treatment of HER2-positive breast cancer. METHODS: A
      review of the biomedical literature published prior to February 2013 was
      conducted in English using PubMed. ClinicalTrials.gov was searched for
      appropriate clinical trials. The search terms used included breast neoplasm,
      pertuzumab, dimerisation, and HER2-positive. Abstracts of studies presented at
      the ASCO and ESMO Annual Meetings, and San Antonio Breast Cancer Symposium were
      also included. RESULTS: Pertuzumab represents a novel anti-HER2 targeted therapy
      for HER2-positive breast cancers. In this article, we describe the mechanism of
      action of pertuzumab, as well as its drug development process and preclinical
      testing results. Based on the results of ancillary studies, dual inhibition using
      pertuzumab and trastuzumab was shown to be effective for the management of HER2
      positive metastatic breast cancers pre-treated with trastuzumab-based therapy.
      For the first-line setting, the combination of both pertuzumab and trastuzumab
      with docetaxel (CLEOPATRA trial; clinical evaluation of pertuzumab and
      trastuzumab) has changed the paradigm of patient management. CONCLUSION:
      Pertuzumab provided a more comprehensive inhibition of HER2-driven signalling
      pathways. When administered together with trastuzumab, pertuzumab represent a
      significant advancement for the treatment of HER2-positive metastatic breast
      cancer patients.

PMID- 23881723
TI  - Targeting the gut-liver axis in cirrhosis: antibiotics and non-selective beta
      blockers.
AB  - The gut-liver axis in cirrhosis and portal hypertension is gaining increasing
      attention as a key pathophysiological mechanism responsible for progression of
      liver failure and development of complications such as spontaneous infections and
      hepatocellular carcinoma. Antibiotics and non-selective beta-blockers (NSBB)
      intercept this axis and each drug has proven efficacy in clinical trials. A
      synergistic effect is a hitherto unproven possibility. There is an increasing
      body of evidence supporting improved outcome with expanded use of NSBB and
      antibiotic therapy beyond current indications. This review addresses the issue of
      pharmacological treatment of cirrhosis and portal hypertension with antibiotics
      and NSBB. We discuss their mechanism of action and suggest that combining the two
      treatment modalities could potentially reduce the risk of complications. 

PMID- 23881724
TI  - Poly(thymine)-templated selective formation of fluorescent copper nanoparticles.

PMID- 23881725
TI  - Porous nitrogen-doped carbon nanotubes derived from tubular polypyrrole for
      energy-storage applications.
AB  - Porous nitrogen-doped carbon nanotubes (PNCNTs) with a high specific surface area
      (1765 m(2)  g(-1)) and a large pore volume (1.28 cm(3)  g(-1)) have been
      synthesized from a tubular polypyrrole (T-PPY). The inner diameter and wall
      thickness of the PNCNTs are about 55 nm and 22 nm, respectively. This material
      shows extremely promising properties for both supercapacitors and for
      encapsulating sulfur as a superior cathode material for high-performance lithium
      sulfur (Li-S) batteries. At a current density of 0.5 A g(-1), PNCNT presents a
      high specific capacitance of 210 F g(-1), as well as excellent cycling stability
      at a current density of 2 A g(-1). When the S/PNCNT composite was tested as the
      cathode material for Li-S batteries, the initial discharge capacity was 1341 mA h
      g(-1) at a current rate of 1 C and, even after 50 cycles at the same rate, the
      high reversible capacity was retained at 933 mA h g(-1). The promising
      electrochemical energy-storage performance of the PNCNTs can be attributed to
      their excellent conductivity, large surface area, nitrogen doping, and unique
      pore-size distribution.

PMID- 23881726
TI  - Facile synthesis of hydroxy-modified MOF-5 for improving the adsorption capacity
      of hydrogen by lithium doping.
AB  - A facile synthesis of partially hydroxy-modified MOF-5 and its improved H2
      adsorption capacity by lithium doping are reported. The reaction of Zn(NO3)2.6H2O
      with a mixture of terephthalic acid (H2BDC) and 2-hydroxyterephthalic acid (H2BDC
      OH) in DMF gave hydroxy-modified MOF-5 (MOF-5-OH-x), in which the molar fraction
      (x) of BDC-OH(2-) was up to 0.54 of the whole ligand. The MOF-5-OH-x frameworks
      had high BET surface areas (about 3300 m(2) g(-1)), which were comparable to that
      of MOF-5. We suggest that the MOF-5-OH-x frameworks are formed by the secondary
      growth of BDC(2-)-rich MOF-5 seed crystals, which are nucleated during the early
      stage of the reaction. Subsequent Li doping into MOF-5-OH-x results in increased
      H2 uptake at 77 K and 0.1 MPa from 1.23 to 1.39 wt.% and an increased isosteric
      heat of H2 adsorption from 5.1-4.2 kJ mol(-1) to 5.5-4.4 kJ mol(-1).

PMID- 23881727
TI  - Executive summary: a guide to utilization of the microbiology laboratory for
      diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases
      Society of America (IDSA) and the American Society for Microbiology (ASM)(a).
AB  - The critical role of the microbiology laboratory in infectious disease diagnosis
      calls for a close, positive working relationship between the physician and the
      microbiologists who provide enormous value to the health care team. This
      document, developed by both laboratory and clinical experts, provides information
      on which tests are valuable and in which contexts, and on tests that add little
      or no value for diagnostic decisions. Sections are divided into anatomic systems,
      including Bloodstream Infections and Infections of the Cardiovascular System,
      Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of
      the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract
      infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections,
      Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin
      and Soft Tissue Infections; or into etiologic agent groups, including Tickborne
      Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each
      section contains introductory concepts, a summary of key points, and detailed
      tables that list suspected agents; the most reliable tests to order; the samples
      (and volumes) to collect in order of preference; specimen transport devices,
      procedures, times, and temperatures; and detailed notes on specific issues
      regarding the test methods, such as when tests are likely to require a
      specialized laboratory or have prolonged turnaround times. There is redundancy
      among the tables and sections, as many agents and assay choices overlap. The
      document is intended to serve as a reference to guide physicians in choosing
      tests that will aid them to diagnose infectious diseases in their patients. 

PMID- 23881730
TI  - Health information technology in urologic care: current status and implications
      for quality of care.
AB  - Health information technology (HIT) is expected to transform the delivery of
      health care in the United States, but implementation and adoption vary widely
      across settings, specialties, and geographies. Significant barriers to high-level
      adoption persist despite federal incentives to hospitals and health-care
      providers. This article will review the current status and future impact of HIT
      in the specialty of urology, with emphasis on the intersection of HIT and quality
      measurement. 

PMID- 23881728
TI  - Photo quiz. Generalized pain in a 20-year-old man with chronic granulomatous
      disease.

PMID- 23881731
TI  - Mass media interventions for reducing mental health-related stigma.
AB  - BACKGROUND: Mental health-related stigma is widespread and has major adverse
      effects on the lives of people with mental health problems. Its two major
      components are discrimination (being treated unfairly) and prejudice
      (stigmatising attitudes). Anti-stigma initiatives often include mass media
      interventions, and such interventions can be expensive. It is important to know
      if mass media interventions are effective. OBJECTIVES: To assess the effects of
      mass media interventions on reducing stigma (discrimination and prejudice)
      related to mental ill health compared to inactive controls, and to make
      comparisons of effectiveness based on the nature of the intervention (e.g. number
      of mass media components), the content of the intervention (e.g. type of primary
      message), and the type of media (e.g. print, internet). SEARCH METHODS: We
      searched eleven databases: the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 7, 2011); MEDLINE (OvidSP),1966 to 15
      August 2011; EMBASE (OvidSP),1947 to 15 August 2011; PsycINFO (OvidSP), 1806 to
      15 August 2011; CINAHL (EBSCOhost) 1981 to 16 August 2011; ERIC (CSA), 1966 to 16
      August 2011; Social Science Citation Index (ISI), 1956 to 16 August 2011;
      OpenSIGLE (http://www.opengrey.eu/), 1980 to 18 August 2012; Worldcat
      Dissertations and Theses (OCLC), 1978 to 18 August 2011; metaRegister of
      Controlled Trials (http://www.controlled-trials.com/mrct/mrct_about.asp), 1973 to
      18 August 2011; and Ichushi (OCLC), 1903 to 11 November 2011. We checked
      references from articles and reviews, and citations from included studies. We
      also searched conference abstracts and websites, and contacted researchers.
      SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster RCTs or
      interrupted time series studies of mass media interventions compared to inactive
      controls in members of the general public or any of its constituent groups
      (excluding studies in which all participants were people with mental health
      problems), with mental health as a subject of the intervention and discrimination
      or prejudice outcome measures. DATA COLLECTION AND ANALYSIS: Two authors
      independently extracted data and assessed the risk of bias of included studies.
      We contacted study authors for missing information. Information about adverse
      effects was collected from study reports. Primary outcomes were discrimination
      and prejudice, and secondary outcomes were knowledge, cost, reach, recall, and
      awareness of interventions, duration/sustainability of media effects, audience
      reactions to media content, and unforeseen adverse effects. We calculated
      standardised mean differences and odds ratios. We conducted a primarily narrative
      synthesis due to the heterogeneity of included studies. Subgroup analyses were
      undertaken to examine the effects of the nature, content and type of mass media
      intervention. MAIN RESULTS: We included 22 studies involving 4490 participants.
      All were randomised trials (3 were cluster RCTs), and 19 of the 22 studies had
      analysable outcome data. Seventeen of the studies had student populations. Most
      of the studies were at unclear or high risk of bias for all forms of bias except
      detection bias.Findings from the five trials with discrimination outcomes (n =
      1196) were mixed, with effects showing a reduction, increase or consistent with
      no evidence of effect. The median standardised mean difference (SMD) for the
      three trials (n = 394) with continuous outcomes was -0.25, with SMDs ranging from
      -0.85 (95% confidence interval (CI) -1.39 to -0.31) to -0.17 (95% CI -0.53 to
      0.20). Odds ratios (OR) for the two studies (n = 802) with dichotomous
      discrimination outcomes showed no evidence of effect: results were 1.30 (95% CI
      0.53 to 3.19) and 1.19 (95% CI 0.85 to 1.65).The 19 trials (n = 3176) with
      prejudice outcomes had median SMDs favouring the intervention, at the three
      following time periods: -0.38 (immediate), -0.38 (1 week to 2 months) and -0.49
      (6 to 9 months). SMDs for prejudice outcomes across all studies ranged from -2.94
      (95% CI -3.52 to -2.37) to 2.40 (95% CI 0.62 to 4.18). The median SMDs indicate
      that mass media interventions may have a small to medium effect in decreasing
      prejudice, and are equivalent to reducing the level of prejudice from that
      associated with schizophrenia to that associated with major depression.The
      studies were very heterogeneous, statistically, in their populations,
      interventions and outcomes, and only two meta-analyses within two subgroups were
      warranted. Data on secondary outcomes were sparse. Cost data were provided on
      request for three studies (n = 416), were highly variable, and did not address
      cost-effectiveness. Two studies (n = 455) contained statements about adverse
      effects and neither reported finding any. AUTHORS' CONCLUSIONS: Mass media
      interventions may reduce prejudice, but there is insufficient evidence to
      determine their effects on discrimination. Very little is known about costs,
      adverse effects or other outcomes. Our review found few studies in middle- and
      low-income countries, or with employers or health professionals as the target
      group, and none targeted at children or adolescents. The findings are limited by
      the quality of the evidence, which was low for the primary outcomes for
      discrimination and prejudice, low for adverse effects and very low for costs.
      More research is required to establish the effects of mass media interventions on
      discrimination, to better understand which types of mass media intervention work
      best, to provide evidence about cost-effectiveness, and to fill evidence gaps
      about types of mass media not covered in this review. Such research should use
      robust methods, report data more consistently with reporting guidelines and be
      less reliant on student populations.

PMID- 23881732
TI  - In juvenile dermatomyositis, cardiac systolic dysfunction is present after long
      term follow-up and is predicted by sustained early skin activity.
AB  - OBJECTIVE: To compare systolic cardiac function in patients with juvenile
      dermatomyositis (JDM) with matched controls and examine associations between
      systolic and diastolic cardiac function and disease variables. METHODS: Fifty
      nine patients, examined at follow-up, median 16.8 years (2-38 years) after
      disease onset, were compared with 59 age-matched and sex-matched controls.
      Echocardiography was performed and analysed blinded to patient information. We
      used mitral annulus displacement to assess the relative long-axis shortening of
      the left ventricle (long-axis strain) and early diastolic tissue velocity (e'),
      as markers for systolic and diastolic function, respectively. Disease activity
      and organ damage were assessed at follow-up by clinical examination and
      retrospectively by chart review. RESULTS: Long-axis strain was reduced in
      patients compared with controls (16.6% (2.5) vs 17.7% (2.0), mean (SD), p=0.001),
      whereas no difference was seen between patients with active and inactive disease.
      Disease duration correlated with systolic and diastolic function (rsp=-0.50 and
      rsp=-0.73, both p<0.001) and so did Myositis Damage Index (MDI) 1 year (rsp=-0.36
      and rsp=-0.46) and MDI at follow-up (rsp=-0.33 and rsp=-0.60), all p<0.01. High
      early disease activity score (DAS) in skin (DAS skin 1 year), but not in muscle,
      predicted systolic (standardised beta=-0.28, p=0.011, R(2)=48%) and diastolic
      dysfunction (beta=-0.36, p<0.001, R(2)=72%) at follow-up. CONCLUSIONS: Long-axis
      strain was reduced in JDM patients compared with controls, suggesting systolic
      dysfunction. Impaired systolic and diastolic function was predicted by DAS skin 1
      year. This indicates a common pathway to two different cardiac manifestations in
      JDM, perhaps with similar pathogenesis as skin affection.

PMID- 23881733
TI  - Alzheimer's disease pathology in the neocortex and hippocampus of the western
      lowland gorilla (Gorilla gorilla gorilla).
AB  - The two major histopathologic hallmarks of Alzheimer's disease (AD) are amyloid
      beta protein (Abeta) plaques and neurofibrillary tangles (NFT). Abeta pathology
      is a common feature in the aged nonhuman primate brain, whereas NFT are found
      almost exclusively in humans. Few studies have examined AD-related pathology in
      great apes, which are the closest phylogenetic relatives of humans. In the
      present study, we examined Abeta and tau-like lesions in the neocortex and
      hippocampus of aged male and female western lowland gorillas using
      immunohistochemistry and histochemistry. Analysis revealed an age-related
      increase in Abeta-immunoreactive plaques and vasculature in the gorilla brain.
      Abeta plaques were more abundant in the neocortex and hippocampus of females,
      whereas Abeta-positive blood vessels were more widespread in male gorillas.
      Plaques were also Abeta40-, Abeta42-, and Abeta oligomer-immunoreactive, but only
      weakly thioflavine S- or 6-CN-PiB-positive in both sexes, indicative of the less
      fibrillar (diffuse) nature of Abeta plaques in gorillas. Although phosphorylated
      neurofilament immunostaining revealed a few dystrophic neurites and neurons,
      choline acetyltransferase-immunoreactive fibers were not dystrophic. Neurons
      stained for the tau marker Alz50 were found in the neocortex and hippocampus of
      gorillas at all ages. Occasional Alz50-, MC1-, and AT8-immunoreactive astrocyte
      and oligodendrocyte coiled bodies and neuritic clusters were seen in the
      neocortex and hippocampus of the oldest gorillas. This study demonstrates the
      spontaneous presence of both Abeta plaques and tau-like lesions in the neocortex
      and hippocampus in old male and female western lowland gorillas, placing this
      species at relevance in the context of AD research.

PMID- 23881737
TI  - Evaluation of the multifrequency electronic apex locator Joypex 5 in primary
      teeth.
AB  - AIM: To evaluate ex vivo the accuracy of the multifrequency electronic apex
      locator (EAL) Joypex 5 in primary molars. METHODS: Fourteen primary molars were
      selected for a total of 25 root canals. Working length measurements were
      performed by direct observation (DO), using a 15 K-file into the root canal until
      its tip was visible at the apical foramen and electronically using the EALs
      Joypex 5. Data were analysed statistically using the intraclass correlation
      coefficient (ICC). To assess whether a significant difference in accuracy of the
      electronic apex locator existed, the Student's t test was performed at 5%
      significance. RESULTS: No statistical difference was observed between the direct
      observation and the EAL measurement (p < 0.05). The ICC confirmed the agreement
      of different methods to measure canal length. The R(2) coefficient was close to
      1, denoting a strong agreement between measures obtained with Joypex 5 and DO.
      CONCLUSION: The multifrequency EALs Joypex 5 showed adequate accuracy in the root
      length determination of primary teeth.

PMID- 23881738
TI  - Inversion of enantioselectivity of a mononuclear non-heme iron(II)-dependent
      hydroxylase by tuning the interplay of metal-center geometry and protein
      structure.

PMID- 23881739
TI  - Cross-species sensitivity to a novel androgen receptor agonist of potential
      environmental concern, spironolactone.
AB  - Spironolactone is a pharmaceutical that in humans is used to treat conditions
      like hirsutism, various dermatologic afflictions, and female-pattern hair loss
      through antagonism of the androgen receptor. Although not routinely monitored in
      the environment, spironolactone has been detected downstream of a pharmaceutical
      manufacturer, indicating a potential for exposure of aquatic species.
      Furthermore, spironolactone has been reported to cause masculinization of female
      western mosquitofish, a response indicative of androgen receptor activation.
      Predictive methods to identify homologous proteins to the human and western
      mosquitofish androgen receptor suggest that vertebrates would be more susceptible
      to adverse effects mediated by chemicals like spironolactone that target the
      androgen receptor compared with invertebrate species that lack a relevant
      homolog. In addition, an adverse outcome pathway previously developed for
      activation of the androgen receptor suggests that androgen mimics can lead to
      reproductive toxicity in fish. To assess this, 21-d reproduction studies were
      conducted with 2 fish species, fathead minnow and Japanese medaka, and the
      invertebrate Daphnia magna. Spironolactone significantly reduced the fecundity of
      medaka and fathead minnows at 50 MUg/L, whereas daphnia reproduction was not
      affected by concentrations as large as 500 MUg/L. Phenotypic masculinization of
      females of both fish species was observed at 5 MUg/L as evidenced by formation of
      tubercles in fathead minnows and papillary processes in Japanese medaka. Effects
      in fish occurred at concentrations below those reported in the environment. These
      results demonstrate how a priori knowledge of an adverse outcome pathway and the
      conservation of a key molecular target across vertebrates can be utilized to
      identify potential chemicals of concern in terms of monitoring and highlight
      potentially sensitive species and endpoints for testing.

PMID- 23881740
TI  - Absolute asymmetric synthesis of enantiopure organozinc reagents, followed by
      highly enantioselective chlorination.
AB  - We report the absolute asymmetric synthesis (AAS) of indenylzinc reagents by
      using total spontaneous resolution followed by enantiospecific conversion into 1
      chloroindene. The chiral complex [Zn(dcp)(ind)(tmeda)] (dcp = 2,6-dichlorophenoxy
      and tmeda = N,N,N',N'-tetramethylethylenediamine) (3) was prepared from the
      achiral starting materials indene, potassium, zinc chloride, TMEDA, and 2,6
      dichlorophenol. The reagent resolved spontaneously on crystallization, and single
      crystals of 3 react with N-chlorosuccinimide in the presence of benzoquinone in 2
      propanol to give 1-chloroindene in >98 % enantiomeric excess. It was found that
      (R)-3 gave (R)-1-chloroindene upon reaction, indicating an SE 2'-mechanism. Since
      bulk samples of 3 gave optically active product upon chlorination, total
      spontaneous resolution must have occurred. This demonstrates that enantiopure
      products can be obtained through the absolute asymmetric synthesis of
      organometallic reagents starting from achiral materials. The general absolute
      asymmetric synthesis (AAS) method offers easy access to both enantiomers and an
      almost limitless variation in the design of the product.

PMID- 23881741
TI  - Imidazolium-based poly(ionic liquid)s as new alternatives for CO2 capture.
AB  - Solid imidazolium-based poly(ionic liquid)s with variable molecular weights that
      contain the poly[2-(1-butylimidazolium-3-yl)ethyl methacrylate] (BIEMA) cation
      and different counter anions were evaluated in terms of CO2 capture and compared
      with classical ionic liquids with similar counter anions. In addition to
      poly(ionic liquid)s with often-applied ions such as BF4 (-) , PF6 (-) , NTf2 (-)
      , trifluoromethanesulfonate (OTf(-) ) and Br(-) , for the first time
      [BIEMA][acetate] was synthesised, which revealed a remarkably high CO2 sorption
      performance that exceeded the poly(ionic liquid)s studied previously on average
      by a factor of four (12.46 mg gPIL (-1) ). This study provides an understanding
      of the factors that affect CO2 sorption and a comparison of the CO2 capture
      efficiency with the frequently used sorbents. Moreover, all the studied sorbents
      were reusable if regenerated under carefully selected conditions and can be
      considered as suitable candidates for CO2 sorption.

PMID- 23881743
TI  - Gary W. Van Hoesen, Ph.D. (1942-2012) in memoriam.

PMID- 23881742
TI  - Update on treatment of essential tremor.
AB  - OPINION STATEMENT: Essential tremor is one of the most common movement disorders
      in the world. Although millions of people worldwide are affected by ET, only one
      medication, propranolol, is approved by the United States Food and Drug
      Administration to treat it. None of the medications currently used as ET therapy
      were developed specifically for this purpose, and select antihypertensive and
      antiepileptic medications remain at the forefront of ET therapy. Propranolol and
      primidone are considered "effective" agents that treat ET; topiramate, atenolol,
      and alprazolam are "probably effective", and nimodipine, nadolol, and clonazepam
      are "possibly effective". Medications that probably do not adequately treat ET
      include levetiracetam and pregabalin. Gabapentin appears to improve ET when used
      as monotherapy, but not when used as adjunct therapy. Sotalol has been found to
      be "probably effective" in treating ET in previous reviews, but it may be
      associated with arrhythmias and should not be routinely recommended. Botulinum
      toxin A may reduce limb tremor, but may cause dose dependent weakness. Deep brain
      stimulation (DBS) of the VIM is used as an alternative to pharmacological therapy
      of ET in patients who fail to adequately respond to medical therapy. The
      magnitude of effect from DBS is greater than from medical management, but more
      severe side effects are possible with surgery. Future treatment options for ET
      will depend on valid animal models, and a better understanding of its
      pathophysiology.

PMID- 23881744
TI  - Early versus late administration of amino acids in preterm infants receiving
      parenteral nutrition.
AB  - BACKGROUND: Observational studies in preterm newborns suggest that delay in
      administering amino acids could result in a protein catabolic state and could
      impact on growth and development. OBJECTIVES: To determine the effect of early
      administration of amino acids in premature newborns on growth, neurodevelopmental
      outcome, mortality and clinically important side effects. SEARCH METHODS: The
      standard search strategy of the Neonatal Review Group as outlined in The Cochrane
      Library was used. Relevant randomised controlled trials were identified by
      searching the Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library 2012 I ssue 9 ), MEDLINE, EMBASE and CINAHL from their earliest
      dates to September 2012. The trial registry portal of the World Health
      Organization's International Cilinical Trial Registry Platform and
      ClinicalTrials.gov (US National Institute of Health) was searched to identify
      ongoing and completed but unpublished studies. SELECTION CRITERIA: Randomised
      controlled trials comparing early administration of amino acids with late
      administration in premature newborn infants were included. Early administration
      of amino acid solution was defined as the administration of amino acids in
      isolation or with total parenteral nutrition within the first 24 hours of birth;
      late initiation was defined as the administration of amino acids in isolation or
      with total parenteral nutrition after the first 24 hours of birth. The primary
      outcome measures were growth, neurodevelopmental outcome and mortality at 28
      days. The secondary outcomes were biochemical abnormalities, sepsis and
      mortality. DATA COLLECTION AND ANALYSIS: Both review authors independently
      selected trials, assessed trial quality and extracted data from the included
      studies. We contacted authors for further information. Fixed-effect analyses were
      performed. The treatment effect was expressed as mean difference for continuous
      variables and as risk difference and risk ratio for dichotomous variables. All
      results included 95% confidence intervals (CIs). MAIN RESULTS: Seven randomised
      controlled trials were included in this review. One randomised controlled trial
      reported no difference in crown-heel length and occipitofrontal head
      circumference by day 10. Four trials that enrolled 93 premature infants showed
      positive nitrogen balance (The mean difference with 95% CI was 250.42 (224.91 to
      275.93 P value < 0.00001). Four trials showed a significant difference in the
      level of blood urea nitrogen (BUN) in the first 48 hours (P value < 0.00001).
      Early administration of amino acids did not result in metabolic acidosis in the
      first 24 hours. AUTHORS' CONCLUSIONS: There is no available evidence of the
      benefits of early administration of amino acids on mortality, early and late
      growth and neurodevelopment. There is evidence from four randomised controlled
      trials included in this review that early administration of amino acids is
      associated with a positive nitrogen balance. The clinical relevance of this
      finding is not known. Acid-base status and ammonia levels were normal in the
      infants who received amino acids early. Given the small number of infants in the
      randomised controlled trials included in this review, the clinical heterogeneity
      among them, and the lack of data on important clinical outcomes, there is
      insufficient evidence to guide practice regarding the early versus late
      administration of amino acids to infants less than 37 weeks gestation.

PMID- 23881748
TI  - Enantioselective hydrogenation of isoquinolines.

PMID- 23881747
TI  - Thought-shape fusion in anorexia and bulimia nervosa: a comparative experimental
      study.
AB  - 'Thought-shape fusion' (TSF) is a cognitive distortion specific in patients with
      eating disorders and occurs when the thought about eating a forbidden food
      increases a person's estimate of her weight/shape, elicits a perception of moral
      wrongdoing and makes her feel fat. This study aimed to experimentally induce,
      study and compare TSF between patients with bulimia nervosa (BN) and patients
      with anorexia nervosa (AN). 31 patients diagnosed with a current eating disorder,
      of which 20 met DSM-IV-TR criteria for BN and 11 for AN, participated in a mixed
      model experimental design with the aim of eliciting TSF and investigating the
      effects of corrective behaviors (checking and mental neutralizing). Verbal
      analogue scales constituted the main outcome measures. TSF was experimentally
      induced and expressed in a similar way in both clinical groups, apart from
      'feeling fat' which was higher in BN patients. TSF induction triggered heightened
      levels of anxiety, guilt and urges to engage in corrective behaviors in both
      groups. Body dissatisfaction only increased in the BN patients. Mental
      neutralizing and to a lesser extent checking reduced most effects of the
      experimental procedure, but this effect was larger for BN patients. The nature of
      TSF seems to have similarities between BN and AN patients; however, the precise
      connection between TSF and different types of eating disorders remains to be
      explored in future clinical trials.

PMID- 23881749
TI  - Liquid-crystalline ordering as a concept in materials science: from
      semiconductors to stimuli-responsive devices.
AB  - While the unique optical properties of liquid crystals (LCs) are already well
      exploited for flat-panel displays, their intrinsic ability to self-organize into
      ordered mesophases, which are intermediate states between crystal and liquid,
      gives rise to a broad variety of additional applications. The high degree of
      molecular order, the possibility for large scale orientation, and the structural
      motif of the aromatic subunits recommend liquid-crystalline materials as organic
      semiconductors, which are solvent-processable and can easily be deposited on a
      substrate. The anisotropy of liquid crystals can further cause a stimuli
      responsive macroscopic shape change of cross-linked polymer networks, which act
      as reversibly contracting artificial muscles. After illustrating the concept of
      liquid-crystalline order in this Review, emphasis will be placed on synthetic
      strategies for novel classes of LC materials, and the design and fabrication of
      active devices. 

PMID- 23881751
TI  - Epigenetic effects of natural polyphenols: a focus on SIRT1-mediated mechanisms.
AB  - Polyphenols are a class of natural compounds widely distributed in fruits,
      vegetables, and plants. They have been reported to possess a wide range of
      activities in prevention and alleviation of various diseases like cancer,
      neuroinflammation, diabetes, and aging. Polyphenols are effective against chronic
      diseases and recent reports indicated strong epigenetic effects of polyphenols.
      Most of the studies investigating epigenetic effects of natural polyphenols have
      focused on their beneficial effects in cancer treatment. However, epigenetic
      defects have been demonstrated in many other diseases as well, and application of
      polyphenols to modulate the epigenome is becoming an interesting field of
      research. This review summarizes the effects of natural polyphenols in modulating
      epigenetic-related enzymes as well as their effect in prevention and treatment of
      chronic diseases with a focus on SIRT1 modulation. We have also discussed the
      relation between the structure and function of epigenetic-modifying polyphenols. 

PMID- 23881750
TI  - Effects of low levels of herbicides on prairie species of the Willamette Valley,
      Oregon.
AB  - The relative sensitivity of 17 noncrop plant species from Oregon's Willamette
      Valley was determined in response to glyphosate, tribenuron methyl (tribenuron),
      and fluazifop-p-butyl (fluazifop) herbicides. For glyphosate, Elymus
      trachycaulus, Festuca arundinacea, Madia elegans, Potentilla gracilis, and
      Ranunculus occidentalis were the most sensitive species, based on a concentration
      calculated to reduce shoot dry weight by 25% (IC25 values) of 0.02 to 0.04 * a
      field application rate of 1112 g active ingredient (a.i.) per hectare. Clarkia
      amoena and Lupinus albicaulis were the most tolerant to glyphosate, with IC25
      values near the field application rate. Clarkia amoena, Prunella vulgaris, and R.
      occidentalis were the most sensitive to tribenuron, with IC25 values of 0.001 to
      0.004 * a field application rate of 8.7 g a.i. ha(-1) for shoot dry weight. Five
      grass species were tolerant to tribenuron with no significant IC25 values. For
      fluazifop, 2 native grasses, E. trachycaulus and Danthonia californica, were the
      most sensitive species, with IC25 values of 0.007 and 0.010 * a field application
      rate of 210 g a.i. ha(-1) , respectively, for shoot dry weight, while a native
      grass, Festuca roemeri, and nearly all forbs showed little or no response. These
      results also indicated that the 3 introduced species used in the present study
      may be controlled with 1 of the tested herbicides: glyphosate (F. arundinacea),
      tribenuron (Leucanthemum vulgare), and fluazifop (Cynosurus echinatus).

PMID- 23881752
TI  - Custom-made morphologies of ZnO nanostructured films templated by a poly(styrene
      block-ethylene oxide) diblock copolymer obtained by a sol-gel technique.
AB  - Zinc oxide (ZnO) nanostructured films are synthesized on silicon substrates to
      form different morphologies that consist of foamlike structures, wormlike
      aggregates, circular vesicles, and spherical granules. The synthesis involves a
      sol-gel mechanism coupled with an amphiphilic diblock copolymer poly(styrene
      block-ethylene oxide), P(S-b-EO), which acts as a structure-directing template.
      The ZnO precursor zinc acetate dihydrate (ZAD) is incorporated into the
      poly(ethylene oxide) block. Different morphologies are obtained by adjusting the
      weight fractions of the solvents and ZAD. The sizes of the structure in solution
      for different sol-gels are probed by means of dynamic light scattering. Thin-film
      samples with ZnO nanostructures are prepared by spin coating and solution casting
      followed by a calcination step. On the basis of various selected combinations of
      weight fractions of the ingredients used, a ternary phase diagram is constructed
      to show the compositional boundaries of the investigated morphologies. The
      evolution and formation mechanisms of the morphologies are addressed in brief.
      The surface morphologies of the ZnO nanostructures are studied with SEM. The
      inner structures of the samples are probed by means of grazing incidence small
      angle X-ray scattering to complement the SEM investigations. XRD measurements
      confirm the crystallization of the ZnO in the wurtzite phase upon calcination of
      the nanocomposite film in air. The optical properties of ZnO are analyzed by FTIR
      and UV/Vis spectroscopy. 

PMID- 23881753
TI  - Proton catalysis in the redox responsivity of a mini-sized photochromic
      diarylethene.
AB  - A thermally irreversible dithienylethene (DTE) photochrom can be turned into a
      thermally reversible one in presence of Cu(II) triflate. A ring opening (DTEC
      closed->DTEO open) occurs through the formation of a copper-containing fast
      transient intermediate. Stopped-flow experiments monitored at 410 and 780 nm have
      allowed to show that the stoichiometry of this intermediate is DTE/Cu=1:1. At
      longer monitoring times (i.e., several seconds after mixing), the intermediate
      undergoes a slow decay while the residual DTEC closed form opens. A joint
      detailed kinetic and electrochemical analysis has unveiled a proton catalysis
      scenario in which electron transfer between DTEC and Cu(II), ligand exchange,
      protonation-deprotonation equilibria of the cation radicals and ring opening are
      embedded into two main reaction cycles. At the beginning of the reaction, Cu(II)
      is reduced into Cu(I) and DTE is degraded without ring opening. Then, as the
      reaction progresses, the triflic acid released from the Cu(II) reduction switches
      on a propagation cycle during which ring opens without any more Cu(II)
      consumption. Cyclic voltammetry, spectro-electrochemical measurements, delayed
      photocoloration experiments in presence of Cu(II) and acid-base additions have
      confirmed the main features of the proton catalysis.

PMID- 23881754
TI  - Rapid palpitations: three of a kind?

PMID- 23881755
TI  - Rapid palpitations: three of a kind?

PMID- 23881756
TI  - Predictors of outcome after alcohol septal ablation in patients with hypertrophic
      obstructive cardiomyopathy. Special interest for the septal coronary anatomy.
AB  - BACKGROUND: Alcohol septal ablation (ASA) provides symptomatic relief in most but
      not all patients with hypertrophic obstructive cardiomyopathy (HOCM). Therefore
      we investigated predictors of outcome after ASA. METHODS: Clinical,
      echocardiographic, angiographic and procedural characteristics were analysed in
      113 consecutive patients. Successful ASA was defined as NYHA <= 2 with
      improvement of at least 1 class combined with a resting gradient < 30 mmHg and
      provoked gradient < 50 mmHg at 4-month follow-up. RESULTS: In 37 patients ASA was
      not successful. In multivariate analysis, baseline gradient (OR 1.06 (1.01-1.11)
      per 5 mmHg, p = 0.024) and distance to the ablated septal branch (OR 1.09 (1.03
      1.16) per mm, p = 0.004) were predictors of unsuccessful outcome. The combined
      presence of a non-ablated septal branch and a distance >= 19 mm to the ablated
      branch was a predictor of unsuccessful outcome (OR 5.88 (2.06-16.7), p < 0.001).
      CONCLUSIONS: Baseline gradient and a greater distance from the origin of the left
      anterior descending artery to the ablated septal branch combined with a non
      ablated proximal septal branch are associated with an unsuccessful outcome after
      ASA.

PMID- 23881757
TI  - Outcomes associated with the use of microprocessor-controlled prosthetic knees
      among individuals with unilateral transfemoral limb loss: a systematic review.
AB  - Microprocessor-controlled prosthetic knees (MPKs) have been developed as an
      alternative to non-microprocessor-controlled knees (NMPKs) to address challenges
      facing individuals with lower-limb loss. A body of scientific literature
      comparing MPKs and NMPKs exists but has yet to be critically appraised.
      Therefore, we conducted a systematic review to examine outcomes associated with
      the use of these interventions among individuals with transfemoral limb loss. A
      search of biomedical databases identified 241 publications, of which 27 met the
      inclusion and exclusion criteria and were reviewed for methodological quality and
      content. We developed 28 empirical evidence statements (EESs) in 9 outcome
      categories (metabolic energy expenditure, activity, cognitive demand, gait
      mechanics, environmental obstacle negotiation, safety, preference and
      satisfaction, economics, and health and quality of life) based on findings in the
      literature. The level of evidence supporting these EESs varied due to quantity,
      quality, and consistency of the results. EESs supported by a moderate level of
      evidence that noted significant differences between MPKs and NMPKs were derived
      in five of the nine outcome categories. The results from this review suggest that
      evidence exists to inform clinical practice and that additional research is
      needed to confirm existing evidence and better understand outcomes associated
      with the use of NMPKs and MPKs. 

PMID- 23881758
TI  - Review of electrical stimulation, botulinum toxin, and their combination for
      spastic drop foot.
AB  - Spastic drop foot is a functional impairment causing significant morbidity and
      mortality. Multiple treatments are available for this condition, but it is often
      not clear which treatment or combination of treatments is optimal for a given
      patient. One relatively recent therapy is the use of functional electrical
      stimulation to stimulate the peroneal nerve. Another is the use of botulinum
      toxin injections in the spastic ankle plantar flexors. While reasons exist to
      think these two treatments might work effectively in combination, there is no
      clear consensus in the literature. In this article, I review the background of
      the pathophysiology of spastic drop foot and its treatment options. I present
      some of the theoretical reasons why functional electrical stimulation and
      botulinum toxin injections could work synergistically and present a literature
      review on the topic. Recommendations for future research are discussed. 

PMID- 23881759
TI  - Needs and concerns of male combat Veterans with mild traumatic brain injury.
AB  - Traumatic brain injury (TBI) has emerged as a major cause of morbidity among U.S.
      servicemembers who have served in Iraq and Afghanistan. Even mild TBI (mTBI) can
      result in cognitive impairments that can affect the community reintegration of
      Veterans postdeployment. The purpose of this study was to explore the needs and
      concerns of combat Veterans with mTBI to provide support for an mTBI-specific
      conceptual model (Conceptual Model in the Context of mTBI) derived from Ferrans
      et al.'s health-related quality of life model and the TBI literature. Content
      analysis of qualitative interview data was conducted using a thematic matrix with
      a predetermined code list. Data saturation was achieved after interviews with
      eight male Veterans. Six key categories and predominant themes emerged: cognitive
      impairments, physical symptoms, emotions and behaviors, instrumental activities
      of daily living, interpersonal interactions, and community reintegration.
      Findings provide preliminary support for a new, context-specific conceptual model
      that has the potential to identify areas for future interventions to enhance
      community reintegration of combat Veterans with mTBI. 

PMID- 23881760
TI  - Effect of service dogs on manual wheelchair users with spinal cord injury: a
      pilot study.
AB  - Service dogs help people with mobility impairments. They are trained to perform a
      variety of tasks, such as opening doors, retrieving the telephone, picking up
      objects, and pulling manual wheelchairs (MWCs). More specifically, using the
      traction provided by the service dog has physical benefits because MWC users can
      operate their MWCs with less effort. The objective of this study was to document
      the effect of a service dog on MWC mobility and user shoulder pain, social
      participation, and quality of life. Eleven MWC users with spinal cord injury were
      assessed before and after training with a service dog and 7 mo later. Based on a
      standardized protocol, all study participants learned how to use the service dog
      safely and how to move around efficiently in different environments and under
      different conditions. Results showed that using a service dog increased the
      distance covered by the MWC users and also significantly decreased shoulder pain
      and intensity of effort. Using the service dog also produced slight but
      significant improvements in MWC user skills and social participation and may
      indicate a trend for improvement in quality of life. More extensive research is
      needed to precisely identify the effect of service dogs on the long-term
      management of MWC use. 

PMID- 23881761
TI  - Sex, shoulder pain, and range of motion in manual wheelchair users.
AB  - Upwards of 70% of manual wheelchair users (MWUs) experience shoulder pain. Pain
      is more prevalent among females than males. The causes of this sex discrepancy
      are not understood. Decreased range of motion (ROM) has been suggested as a major
      contributor, but the interaction of sex, ROM, and shoulder pain has not been
      investigated, thus the purpose of this investigation. We divided 30 MWUs (18
      males, 12 females; 21.93 +/- 3.77 yr) into two groups based on self-reported
      shoulder pain: pain group (n = 14; 9 males, 5 females) and no pain group (n = 16;
      9 males, 7 females). We used a digital goniometer to assess ROM. Participants'
      shoulder active and passive ROMs were tested bilaterally on the following joint
      motions: flexion, extension, abduction, adduction, internal rotation, and
      external rotation. We used a visual analog scale to assess shoulder pain. Of the
      participants, 47% reported shoulder pain. Overall, the no pain group had greater
      ROM than the pain group, with further analysis revealing this association was
      only significant in females during extension (p < 0.05). ROM impairments were
      only present in extension in females with shoulder pain. The mechanism underlying
      this sex difference is not clear. 

PMID- 23881762
TI  - Bimanual gliding control for indoor power wheelchair driving.
AB  - Power wheelchairs are essential for many individuals with mobility impairment.
      The objective of this study was to investigate the effectiveness of bimanual
      gliding (BG) and conventional joystick (CJ) control in an indoor environment,
      with application to (1) wheelchair driving performance (i.e., practice time,
      completion time, and driving deviation) and (2) muscle activity of the upper
      limbs. This study included 22 participants (11 experienced manual wheelchair
      users and 11 novice manual wheelchair users). Experienced wheelchair users who
      used the BG strategy needed less time to practice and complete the task. Muscle
      activity of the upper limbs was focused on the triceps brachii, with relatively
      less use of the wrist muscles while applying the BG strategy. In novice
      wheelchair users, wrist muscles were less involved when using the BG control
      compared with the CJ control. The findings imply that it is feasible to modify
      manual wheelchairs using BG and motors, which can serve as an alternative option
      for wheelchair users. 

PMID- 23881763
TI  - Investigation of robotic-assisted tilt-table therapy for early-stage spinal cord
      injury rehabilitation.
AB  - Damage to the spinal cord compromises motor function and sensation below the
      level of injury, resulting in paralysis and progressive secondary health
      complications. Inactivity and reduced energy requirements result in reduced
      cardiopulmonary fitness and an increased risk of coronary heart disease and
      cardiovascular complications. These risks may be minimized through regular
      physical activity. It is proposed that such activity should begin at the earliest
      possible time point after injury, before extensive neuromuscular degeneration has
      occurred. Robotic-assisted tilt-table therapy may be used during early-stage
      spinal cord injury (SCI) to facilitate stepping training, before orthostatic
      stability has been achieved. This study investigates whether such a stimulus may
      be used to maintain pulmonary and coronary health by describing the acute
      responses of patients with early-stage (<1 yr) motor-complete SCI (cSCI) and
      motor-incomplete SCI (iSCI) to passive, active, and electrically stimulated
      robotic-assisted stepping. Active participation was found to elicit an increased
      response from iSCI patients. The addition of electrical stimulation did not
      consistently elicit further increases. Extensive muscle atrophy was found to have
      occurred in those patients with cSCI, thereby limiting the potential
      effectiveness of electrical stimulation. Active participation in robotic-assisted
      tilt-table therapy may be used to improve cardiopulmonary fitness in iSCI
      patients if implemented as part of a regular training program. 

PMID- 23881764
TI  - Estimating the patient's contribution during robot-assisted therapy.
AB  - Robot-assisted therapy has become increasingly common in neurorehabilitation.
      Sophisticated controllers have been developed for robots to assist and cooperate
      with the patient. It is difficult for the patient to judge to what extent the
      robot contributes to the execution of a movement. Therefore, methods to
      comprehensively quantify the patient's contribution and provide feedback are of
      key importance. We developed a method comprehensively to estimate the patient's
      contribution by combining kinematic measures and the motor assistance applied.
      Inverse dynamic models of the robot and the passive human arm calculate the
      required torques to move the robot and the arm and build, together with the
      recorded motor torque, a metric (in percentage) that represents the patient's
      contribution to the movement. To evaluate the developed metric, 12 nondisabled
      subjects and 7 patients with neurological problems simulated instructed movement
      contributions. The results are compared with a common performance metric. The
      estimation shows very satisfying results for both groups, even though the arm
      model used was strongly simplified. Displaying this metric to patients during
      therapy can potentially motivate them to actively participate in the training. 

PMID- 23881765
TI  - Selection of muscle and nerve-cuff electrodes for neuroprostheses using
      customizable musculoskeletal model.
AB  - Neuroprosthetic systems based on functional electrical stimulation aim to restore
      motor function to individuals with paralysis following spinal cord injury.
      Identifying the optimal electrode set for the neuroprosthesis is complicated
      because it depends on the characteristics of the individual (such as injury
      level), the force capacities of the muscles, the movements the system aims to
      restore, and the hardware limitations (number and type of electrodes available).
      An electrode-selection method has been developed that uses a customized
      musculoskeletal model. Candidate electrode sets are created based on desired
      functional outcomes and the hard ware limitations of the proposed system. Inverse
      dynamic simulations are performed to determine the proportion of target movements
      that can be accomplished with each set; the set that allows the most movements to
      be performed is chosen as the optimal set. The technique is demonstrated here for
      a system recently developed by our research group to restore whole-arm movement
      to individuals with high-level tetraplegia. The optimal set included selective
      nerve-cuff electrodes for the radial and musculocutaneous nerves; single-channel
      cuffs for the axillary, suprascapular, upper subscapular, and long-thoracic
      nerves; and muscle-based electrodes for the remaining channels. The importance of
      functional goals, hardware limitations, muscle and nerve anatomy, and surgical
      feasibility are highlighted. 

PMID- 23881766
TI  - Design and development of ankle-foot prosthesis with delayed release of
      plantarflexion.
AB  - A computer-controlled mechanism that fits a standard ankle-foot prosthesis was
      designed to capture the absorbed energy in the ankle and delay its release until
      specific times in the gait cycle. This mechanism used a direct current motor to
      take up and hold the compression of a carbon-fiber ankle joint. Based on the
      timing of the contact forces between the foot and the ground, a microprocessor
      released the spring at preset times later in the gait cycle. This mechanism was
      added to a Talux prosthetic foot and was employed by a user of a conventional
      energy-storage ankle-foot prosthesis. His gait was recorded using a motion
      analysis system. Five settings: 0, 55, 65, 75, and 85 ms delay were tested on
      separate days, and the standard kinematic and kinetic gait data were recorded.
      The user reported some settings were more comfortable than others. When these
      preferences were tested with a randomized double-blind trial, the preferences
      were not consistent. A second user showed a preference for the 55 ms delay. The
      modifications to the device resulted in changes to the gait of the subjects,
      including increased cadence and kinematics of the unaffected joints and a longer,
      slower push from the ankle, which was noticed by both of the subjects. 

PMID- 23881767
TI  - Experimental characterization of axillary/underarm interface pressure in swing
      through crutch walking.
AB  - Supporting weight on the upper support of crutches is not recommended because it
      can lead to axillary nerve damage. Despite this warning, improper axillary
      loadings may still occur because of a lack of arm strength or fatigue. It is
      generally accepted that improper use of conventional axillary crutches
      contributes to axillary nerve damage, but surprisingly there are no studies
      characterizing axillary support/underarm configurations. In this study, we
      compared traditional and horizontal axillary support designs by measuring various
      biomechanical parameters on the axillary support during a swing-through gait
      while supporting weight on the axillary support. Subjects found the axillary
      support that remains horizontal to be more comfortable than the axillary support
      of axillary crutches. The higher perceived comfort may be attributed to the lower
      force and contact area, both average and maximum, developed on the horizontal
      axillary support and/or shorter excursion of the position of the center of force
      during a stride. These findings suggest that avoiding all weight bearing on the
      axillary support may be an overly conservative recommendation for supports that
      remain horizontal. Individuals with insufficient arm strength may benefit by
      considering this type of support, but because further study is needed, a physical
      therapist should be consulted. 

PMID- 23881768
TI  - Temporal adaptations in generic and population-specific quality of life and falls
      efficacy in men with recent lower-limb amputations.
AB  - This study examined the longitudinal changes in generic health-related quality of
      life (QOL), prosthesis-related QOL, falls efficacy, and walking speed in men with
      lower-limb amputations up to 6 months following discharge from rehabilitation.
      Seven male unilateral transtibial amputees completed the Medical Outcomes Study
      36-Item Short Form Health Survey, the Prosthesis Evaluation Questionnaire, and
      the Modified Falls Efficacy Scale at 1, 3, and 6 months postdischarge from
      rehabilitation. Walking speed was also recorded to objectively assess
      participants' mobility. Health-related QOL measures displayed increases,
      resulting in large effect sizes though not reaching statistical significance.
      Prosthesis-related QOL measures indicated that scales relating to the
      participants' prostheses improved and the support of significant others was the
      most positively scored variable. Walking speed increased by 0.12 m/s, although it
      was not significantly related to indices of QOL or falls efficacy. Falls efficacy
      did not improve significantly during the study period, although it was strongly
      related to QOL (p < 0.05). These results provide a novel insight into how QOL and
      falls efficacy develop in people with lower-limb amputations, alongside changes
      in mobility, after discharge from rehabilitation. Further improvements in
      physical health following discharge may be required to elicit subsequent
      increases in overall QOL and concurrent improvements in falls efficacy. 

PMID- 23881769
TI  - Heart rate variability and phantom pain in male amputees: application of linear
      and nonlinear methods.
AB  - Phantom-limb pain (PLP) is a phenomenon that may appear among people with
      amputation. Some studies reveal that 70% of people with amputation experience PLP
      years postamputation. There is a lack of scientific evidence about the cause of
      PLP. It has been hypothesized that the autonomic nervous system (ANS) could be
      involved in the mechanism that triggers PLP, but this hypothesis remains unclear.
      The aim of this study was to correlate ANS function, through heart rate
      variability (HRV) analysis, with PLP in adult males with amputation. The study
      population comprised 35 subjects, with 27 reporting PLP often or always. The rest
      of the subjects did not report any PLP. In order to calculate linear and
      nonlinear parameters of HRV, all subjects underwent 10 min of resting heart rate
      monitoring. The study did not find correlations between HRV parameters and PLP.
      Most of the subjects showed decreased values in linear parameters of HRV while
      nonlinear values were normal. HRV is not implicated in PLP. Linear and nonlinear
      methods for HRV analysis might reflect different physiological phenomena; while
      linear values place people with amputation at cardiovascular risk, nonlinear
      values indicate normality. 

PMID- 23881771
TI  - Pyridine-directed palladium-catalyzed phosphonation of C(sp2)-H bonds.

PMID- 23881770
TI  - Guest editorial: emergent themes from second annual symposium on regenerative
      rehabilitation, Pittsburgh, Pennsylvania.

PMID- 23881772
TI  - Collection of peripheral blood stem cells from a 7 month-old girl weighing 7 kg
      with the use of combined heparin and citrate anticoagulation.

PMID- 23881773
TI  - Well-defined nanofibers with tunable morphology from spherical colloidal building
      blocks.
AB  - From particles to fibers: Nanofibers with different morphologies and
      periodicities can be fabricated by supraparticular assembly of magnetic spherical
      nanoparticles. A linear sintering process is used to merge the assembled colloids
      together. The structure of the obtained fibers is controlled by the process
      parameters and the morphology of the spherical colloidal building blocks.

PMID- 23881774
TI  - Soy fiber improves weight loss and lipid profile in overweight and obese adults:
      a randomized controlled trial.
AB  - SCOPE: Studies have suggested that food rich in dietary fiber may facilitate body
      weight loss, lower total and LDL-cholesterol levels, and reduce body fat. This
      study examined the effects of soy fiber (SF) on body weight, body composition,
      and blood lipids in overweight and obese participants. METHODS AND RESULTS:
      Thirty-nine overweight and obese college adults (19-39 years of age) were
      randomly assigned to consume control biscuits or biscuits supplemented with SF
      for their breakfast for 12 wk (approximately 100 g/day). There were significant
      differences in changes on body weight, BMI, and LDL-cholesterol (LDL-C) between
      the two groups after 12-wk intervention (p < 0.05). The changes of body weight,
      BMI, waist circumference, diastolic blood pressure, serum levels of total
      cholesterol, LDL-C, and glucose, body fat, and trunk fat of participants in SF
      group were observed significantly after 12 wk. CONCLUSION: SF had favorable
      effects on body weight, BMI, and fasting LDL-C levels in overweight and obese
      adults. These effects may be beneficial in antiobesity and the improvement of
      hyperlipidemia and hypertension (ClinicalTrials.gov registration number
      NCT01802840).

PMID- 23881775
TI  - Castor oil, bath and/or enema for cervical priming and induction of labour.
AB  - BACKGROUND: Castor oil, a potent cathartic, is derived from the bean of the
      castor plant. Anecdotal reports, which date back to ancient Egypt have suggested
      the use of castor oil to stimulate labour. Castor oil has been widely used as a
      traditional method of initiating labour in midwifery practice. Its role in the
      initiation of labour is poorly understood and data examining its efficacy within
      a clinical trial are limited. This is one of a series of reviews of methods of
      cervical ripening and labour induction using standardised methodology.
      OBJECTIVES: To determine the effects of castor oil or enemas for third trimester
      cervical ripening or induction of labour in comparison with other methods of
      cervical ripening or induction of labour. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and
      bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing
      castor oil, bath or enemas used for third trimester cervical ripening or labour
      induction with placebo/no treatment or other methods listed above it on a
      predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: A
      strategy was developed to deal with the large volume and complexity of trial data
      relating to labour induction. This involved a two-stage method of data
      extraction. MAIN RESULTS: Three trials, involving 233 women, are included. There
      was no evidence of differences in caesarean section rates between the two
      interventions in the two trials reporting this outcome (risk ratio (RR) 2.04, 95%
      confidence interval (CI) 0.92 to 4.55). There were no data presented on neonatal
      or maternal mortality or morbidity.There was no evidence of a difference between
      castor oil and placebo/no treatment for the rate of instrumental delivery,
      meconium-stained liquor, or Apgar score less than seven at five minutes. The
      number of participants was too small to detect all but large differences in
      outcome. All women who ingested castor oil felt nauseous (RR 59.92, 95% CI 8.46
      to 424.52). AUTHORS' CONCLUSIONS: The three trials included in the review contain
      small numbers of women. All three studies used single doses of castor oil. The
      results from these studies should be interpreted with caution due to the risk of
      bias introduced due to poor methodological quality. Further research is needed to
      attempt to quantify the efficacy of castor oil as an cervical priming and
      induction agent.

PMID- 23881777
TI  - Enhanced stability of (111)-surface-dominant core-shell nanoparticle catalysts
      towards the oxygen reduction reaction.

PMID- 23881776
TI  - Comparative survey of the topographical distribution of signature molecular
      lesions in major neurodegenerative diseases.
AB  - An understanding of the anatomic distributions of major neurodegenerative disease
      lesions is important to appreciate the differential clinical profiles of these
      disorders and to serve as neuropathological standards for emerging molecular
      neuroimaging methods. To address these issues, here we present a comparative
      survey of the topographical distribution of the defining molecular
      neuropathological lesions among 10 neurodegenerative diseases from a large and
      uniformly assessed brain collection. Ratings of pathological severity in 16 brain
      regions from 671 cases with diverse neurodegenerative diseases are summarized and
      analyzed. These include: 1) amyloid-beta and tau lesions in Alzheimer's disease;
      2) tau lesions in three other tauopathies including Pick's disease, progressive
      supranuclear palsy and corticobasal degeneration; 3) alpha-synuclein inclusion
      ratings in four synucleinopathies including Parkinson's disease, Parkinson's
      disease with dementia, dementia with Lewy bodies, and multiple system atrophy;
      and 4) TDP-43 lesions in two TDP-43 proteinopathies, including frontotemporal
      lobar degeneration associated with TDP-43 and amyotrophic lateral sclerosis. The
      data presented graphically and topographically confirm and extend previous
      pathological anatomic descriptions and statistical comparisons highlight the
      lesion distributions that either overlap or distinguish the diseases in each
      molecular disease category.

PMID- 23881778
TI  - Predictive value of electrocardiographic T-wave morphology parameters and T-wave
      peak to T-wave end interval for sudden cardiac death in the general population.
AB  - BACKGROUND: Previous population studies have found an association between
      electrocardiographic T-wave morphology parameters and cardiovascular mortality,
      but their relationship to sudden cardiac death (SCD) is not clear. To our
      knowledge, there are no follow-up studies assessing the association between
      electrocardiographic T-wave peak to T-wave end interval (TPE) and SCD. We
      assessed the predictive value of electrocardiographic T-wave morphology
      parameters and TPE for SCD in an adult general population sample. METHODS AND
      RESULTS: A total of 4 T-wave morphology parameters (principal component analysis
      ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) as
      well as TPE were measured from digital standard 12-lead ECGs in 5618 adults (46%
      men; mean age 50.9+/-12.5 years) participating in the Finnish population-based
      Health 2000 Study. After a mean follow-up time of 7.7+/-1.4 years, 72 SCDs had
      occurred. In univariable analyses, all T-wave morphology parameters were
      associated with an increased SCD risk. In multivariable Cox models, T-wave
      morphology dispersion and total cosine R-to-T remained as predictors of SCD, with
      T-wave morphology dispersion showing the highest SCD risk (hazard ratio of 1.4
      [95% confidence interval 1.1-1.7, P=0.001] per 1 SD increase in the loge T-wave
      morphology dispersion). In contrast, TPE was not associated with SCD in
      univariable or multivariable analyses. CONCLUSIONS: Electrocardiographic T-wave
      morphology parameters describing the 3-dimensional shape of the T-wave stratify
      SCD risk in the general population, but we did not find an association between
      TPE and SCD.

PMID- 23881779
TI  - Impact of stepwise ablation on the biatrial substrate in patients with persistent
      atrial fibrillation and heart failure.
AB  - BACKGROUND: Ablation of persistent atrial fibrillation can be challenging, often
      involving not only pulmonary vein isolation (PVI) but also additional linear
      lesions and ablation of complex fractionated electrograms (CFE). We examined the
      impact of stepwise ablation on a human model of advanced atrial substrate of
      persistent atrial fibrillation in heart failure. METHODS AND RESULTS: In 30
      patients with persistent atrial fibrillation and left ventricular ejection
      fraction <=35%, high-density CFE maps were recorded biatrially at baseline, in
      the left atrium (LA) after PVI and linear lesions (roof and mitral isthmus), and
      biatrially after LA CFE ablation. Surface area of CFE (mean cycle length <=120
      ms) remote to PVI and linear lesions, defined as CFE area, was reduced after PVI
      (18.3+/-12.03 to 10.2+/-7.1 cm(2); P<0.001) and again after linear lesions (7.7+/
      6.5 cm(2); P=0.006). Complete mitral isthmus block predicted greater CFE
      reduction (P=0.02). Right atrial CFE area was reduced by LA ablation, from 25.9+/
      14.1 to 12.9+/-11.8 cm(2) (P<0.001). Estimated 1-year arrhythmia-free survival
      was 72% after a single procedure. Incomplete linear lesion block was an
      independent predictor of arrhythmia recurrence (hazard ratio, 4.69; 95%
      confidence interval, 1.05-21.06; P=0.04). CONCLUSIONS: Remote LA CFE area was
      progressively reduced following PVI and linear lesions, and LA ablation reduced
      right atrial CFE area. Reduction of CFE area at sites remote from ablation would
      suggest either regression of the advanced atrial substrate or that these CFE were
      functional phenomena. Nevertheless, in an advanced atrial fibrillation substrate,
      linear lesions after PVI diminished the target area for CFE ablation, and
      complete lesions resulted in a favorable clinical outcome.

PMID- 23881780
TI  - Biochemical, immunological and kinetic characterisation of thiol protease
      inhibitor (cystatin) from liver.
AB  - Regulation of the cysteine protease activity is imperative for proper functioning
      of the various organ systems. Elevated activities of cysteine proteinases due to
      impaired regulation by the endogenous cysteine proteinase inhibitors (cystatins)
      have been linked to liver malignancies. To gain an insight into these regulatory
      processes, it is essential to purify and characterise the inhibitors, cystatins.
      Present study was undertaken to purify the inhibitor from the liver. The
      purification was accomplished in four steps: alkaline treatment, ammonium
      sulphate fractionation, acetone precipitation and gel filtration column
      (Sephacryl S-100 HR). The eluted protein exhibited inhibitory activity towards
      papain, and its purity was further reaffirmed using western blotting and
      immunodiffusion. The purified inhibitor (liver cystatin (LC)) was stable in the
      pH range of 6-8 and temperature up to 45  degrees C. In view of the significance
      of kinetics parameters for drug delivery, the kinetic parameters of liver
      cystatin were also determined. LC showed the greatest affinity for papain
      followed by ficin and bromelain. UV and fluorescence spectroscopy results showed
      that binding of LC with thiol proteases induced changes in the environment of
      aromatic residues. Recent advances in the field of proteinase inhibitors have
      drawn attention to the possible use of this collected knowledge to control
      pathologies.

PMID- 23881781
TI  - Ficus carica latex-mediated synthesis of silver nanoparticles and its application
      as a chemophotoprotective agent.
AB  - The present work provides scientific support on the use of latex of Ficus carica
      to synthesize stable silver nanoparticles (AgNPs). AgNPs synthesized immediately
      after the addition of latex to silver nitrate solution at room temperature.
      Synthesized nanoparticles were of spherical shape with average size of 163.7 nm.
      Fourier transform infrared spectroscopy analysis revealed capping of proteins and
      phenolic compound on AgNPs, while X-ray diffraction analysis confirmed the fcc
      nature of AgNPs. Particles formed were stable for a long time (6 months). It was
      found that incorporation of AgNPs with 2 and 4% concentration exhibits
      synergistic increase in sun protection factor of commercial sunscreen and natural
      extracts ranging from 01 to 12,175% than control. Further characterization of
      latex and AgNPs revealed total phenolic content of 98.75 and 94.88 MUg/ml. The
      ferric ion reduction potentials of latex and AgNPs were 79.69 and 18.79%.
      Reduction potential of ascorbic acid was synergistically increased after
      cumulative preparation of ascorbic acid with latex and AgNPs and found to be
      106.76 and 101.50% for ascorbic acid + latex and ascorbic acid + AgNPs,
      respectively.

PMID- 23881782
TI  - Phytohormone supplementation significantly increases growth of Chlamydomonas
      reinhardtii cultivated for biodiesel production.
AB  - Cultivation is the most expensive step in the production of biodiesel from
      microalgae, and substantial research has been devoted to developing more cost
      effective cultivation methods. Plant hormones (phytohormones) are chemical
      messengers that regulate various aspects of growth and development and are
      typically active at very low concentrations. In this study, we investigated the
      effect of different phytohormones on microalgal growth and biodiesel production
      in Chlamydomonas reinhardtii and their potential to lower the overall cost of
      commercial biofuel production. The results indicated that all five of the tested
      phytohormones (indole-3-acetic acid, gibberellic acid, kinetin, 1-triacontanol,
      and abscisic acid) promoted microalgal growth. In particular, hormone treatment
      increased biomass production by 54 to 69 % relative to the control growth medium
      (Tris-acetate-phosphate, TAP). Phytohormone treatments also affected microalgal
      cell morphology but had no effect on the yields of fatty acid methyl esters
      (FAMEs) as a percent of biomass. We also tested the effect of these phytohormones
      on microalgal growth in nitrogen-limited media by supplementation in the early
      stationary phase. Maximum cell densities after addition of phytohormones were
      higher than in TAP medium, even when the nitrogen source was reduced to 40 % of
      that in TAP medium. Taken together, our results indicate that phytohormones
      significantly increased microalgal growth, particularly in nitrogen-limited
      media, and have potential for use in the development of efficient microalgal
      cultivation for biofuel production.

PMID- 23881783
TI  - Oil crop biomass residue-based media for enhanced algal lipid production.
AB  - The aim of this study was to evaluate the use of hydrolysates from acid
      hydrolysis of four different oil crop biomass residues (OCBR) as low cost culture
      media for algae growth. The one-factor-at-a-time method was used to design a
      series of experiments to optimize the acid hydrolysis conditions through
      examining the total nitrogen, total phosphorus, chemical oxygen demand, and
      ammonia nitrogen in the hydrolysates. The optimal conditions were found to be
      using 3% sulfuric acid and hydrolyzing residues at 90  degrees C for 20 h. The
      hydrolysates (OCBR media) produced under the optimal conditions were used to
      cultivate the two algae strains, namely UM258 and UM268. The results from 5 days
      of cultivation showed that the OCBR media supported faster algae growth with
      maximal algal biomass yield of 2.7 and 3 g/L, respectively. Moreover, the total
      lipids for UM258 and UM268 were 54 and 35%, respectively, after 5 days of
      cultivation, which suggested that the OCBR media allowed the algae strains to
      accumulate higher lipids probably due to high C/N ratio. Furthermore, over 3% of
      omega-3 fatty acid (EPA) was produced for the two algae strains. In conclusion,
      OCBR media are excellent alternative for algae growth and have a great potential
      for large-scale production of algae-based ingredients for biodiesel as well as
      high-value food and pharmaceutical products.

PMID- 23881784
TI  - Maximizing hydrogen production and substrate consumption by Escherichia coli WDHL
      in cheese whey fermentation.
AB  - Fermentative hydrogen production is strongly affected by pH. In order to maximize
      hydrogen production and substrate consumption in Escherichia coli DeltahycA,
      DeltalacI (WDHL) cheese whey fermentation, the influence of pH control at values
      of 5.5, 6, and 6.5 was studied in batch stirred-tank bioreactors. From the
      conditions evaluated, pH 6.5 was the best condition, at which the highest
      cumulative hydrogen production and yield (1.78 mol H2/mol lactose) were obtained.
      Moreover, at this pH, all carbohydrates from the cheese whey were consumed, and a
      mix of ethanol and organic acids, mainly lactate, were produced from glucose,
      whereas galactose yielded acetate, ethanol, and succinate. Operating the reactor
      at pH 5.5 resulted in the highest maximum specific production rate, but smaller
      hydrogen yield because only glucose was metabolized and galactose was
      accumulated. At pH 6, not all cheese whey carbohydrates were consumed, and it was
      not favorable for hydrogen production. Lactose consumption and growth kinetics
      were not affected by the pH. The results show the importance of controlling pH to
      maximize hydrogen production and substrate consumption using cheese whey as
      substrate.

PMID- 23881785
TI  - Synthesis of functionalized isoquinolin-1(2H)-ones by copper-catalyzed alpha
      arylation of ketones with 2-halobenzamides.
AB  - Copper is key: A concise route to isoquinolin-1(2H)-ones from simple and readily
      available starting materials is provided by an efficient copper-catalyzed
      annulation of ketones with 2-halobenzamides. The method is applicable to a wide
      range of ketones containing different functional groups furnishing the products
      in moderate to excellent yields. 

PMID- 23881786
TI  - Tetracyanoquaterrylene and tetracyanohexarylenequinodimethanes with tunable
      ground states and strong near-infrared absorption.

PMID- 23881787
TI  - Laparoscopic and endoscopic exploration of the ascending colon wall based on a
      cadaver sectioned images.
AB  - For realistic virtual dissection, the sectioned images of a cadaver are a
      desirable material because of their high resolution and real body color. After a
      volume model is made of the sectioned images, it can be piled or peeled at the
      intended thickness as if a structure's surface is expanded and shrunken. The
      purpose of our study was to confirm whether laparoscopic and endoscopic
      exploration of the processed volume model plays a part in anatomy investigation.
      The ascending colon was outlined in serially sectioned images and accumulated to
      build a volume model. While the volume model was being piled or peeled, the
      ascending colon was observed laparoscopically and endoscopically in comparison
      with the original sectioned image. The trial efficiently demonstrated layers of
      the colon wall and surrounding tissues which could not be visualized by
      conventional macroscopic or microscopic techniques. The availability and
      contribution of this new method will be confirmed by application to other various
      organs. 

PMID- 23881788
TI  - Methylation-specific multiplex ligation-dependent probe amplification: utility
      for prenatal diagnosis of parental origin in human triploidy.
AB  - OBJECTIVE: When a triploid pregnancy is diagnosed prenatally, gynaecologists have
      traditionally relied on the histopathological examination of the tissue from the
      terminated pregnancy to determine if the pregnancy is molar. However,
      reproducibility is poor and variability is high when diagnosing hydatidiform
      moles. Triploid pregnancies can have either the chromosomal constitution of two
      maternal and one paternal set, or two paternal and one maternal set, but only the
      conceptuses with two paternal sets have the potential to cause maternal
      complications. Therefore, it would be beneficial to introduce a method that gives
      the gynaecologist the parental origin of the genome of the triploid conceptus as
      early as possible, without delaying the process by first collecting parental
      samples. METHODS: Using methylation-specific multiplex ligation-dependent probe
      amplification, we measured methylation levels at different imprinted sites.
      RESULTS: We were able to correctly determine the parental origin of the genome in
      all 105 triploid pregnancies analysed. CONCLUSIONS: We present methylation
      specific multiplex ligation-dependent probe amplification as a method capable of
      determining the parental origin of the genome of triploid conceptuses within 24
      h; it is inexpensive, simple and easy to use, and parental samples are not
      needed.

PMID- 23881789
TI  - CXCR4 antagonism attenuates load-induced periosteal bone formation in mice.
AB  - Mechanical loading is a key anabolic regulator of bone mass. Stromal cell-derived
      factor-1 (SDF-1) is a stem cell homing factor that is important in hematopoiesis,
      angiogenesis, and fracture healing, though its involvement in skeletal
      mechanoadaptation is virtually unknown. The objective of this study was to
      characterize skeletal expression patterns of SDF-1 and CXCR4, the receptor for
      SDF-1, and to determine the role of SDF-1 signaling in load-induced periosteal
      bone formation. Sixteen-week-old C57BL/6 mice were treated with PBS or AMD3100,
      an antagonist against CXCR4, and exposed to in vivo ulnar loading (2.8 N peak-to
      peak, 2 Hz, 120 cycles). SDF-1 was expressed in cortical and trabecular
      osteocytes and marrow cells, and CXCR4 was primarily expressed in marrow cells.
      SDF-1 and CXCR4 expression was enhanced in response to mechanical stimulation.
      The CXCR4 receptor antagonist AMD3100 significantly attenuated load-induced bone
      formation and led to smaller adaptive changes in cortical geometric properties as
      determined by histomorphometric analysis. Our data suggest that SDF-1/CXCR4
      signaling plays a critical role in skeletal mechanoadaptation, and may represent
      a unique therapeutic target for prevention and treatment of age-related and
      disuse bone loss.

PMID- 23881790
TI  - CoBi3: a binary cobalt-bismuth compound and superconductor.

PMID- 23881791
TI  - Pharmacotherapy for the prevention of chronic pain after surgery in adults.
AB  - BACKGROUND: Chronic pain can often occur after surgery, substantially impairing
      patients' health and quality of life. It is caused by complex mechanisms that are
      not yet well understood. The predictable nature of most surgical procedures has
      allowed for the conduct of randomized controlled trials of pharmacological
      interventions aimed at preventing chronic postsurgical pain. OBJECTIVES: The
      primary objective was to evaluate the efficacy of systemic drugs for the
      prevention of chronic pain after surgery by examining the proportion of patients
      reporting pain three months or more after surgery. The secondary objective was to
      evaluate the safety of drugs administered for the prevention of chronic pain
      after surgery. SEARCH METHODS: We identified randomized controlled trials (RCTs)
      of various systemically administered drugs for the prevention of chronic pain
      after surgery from CENTRAL, MEDLINE, EMBASE and handsearches of other reviews and
      trial registries. The most recent search was performed on 17 July 2013.  
      SELECTION CRITERIA: Included studies were double-blind, placebo-controlled,
      randomized trials involving adults and evaluating one or more drugs administered
      systemically before, during or after surgery, or both, which measured pain three
      months or more after surgery. DATA COLLECTION AND ANALYSIS: Data collected from
      each study included the study drug name, dose, route, timing and duration of
      dosing; surgical procedure; proportion of patients reporting any pain three
      months or more after surgery, reporting at least 4/10 or moderate to severe pain
      three months or more after surgery; and proportion of participants dropping out
      of the study due to treatment-emergent adverse effects. MAIN RESULTS: We
      identified 40 RCTs of various pharmacological interventions including intravenous
      ketamine (14 RCTs), oral gabapentin (10 RCTs), oral pregabalin (5 RCTs), non
      steroidal anti-inflammatories (3 RCTs), intravenous steroids (3 RCTs), oral N
      methyl-D-aspartate (NMDA) blockers (3 RCTs), oral mexiletine (2 RCTs),
      intravenous fentanyl (1 RCT), intravenous lidocaine (1 RCT), oral venlafaxine (1
      RCT) and inhaled nitrous oxide (1 RCT). Meta-analysis suggested a modest but
      statistically significant reduction in the incidence of chronic pain after
      surgery following treatment with ketamine but not gabapentin or pregabalin.
      Results with ketamine should be viewed with caution since most of the included
      trials were small (that is < 100 participants per treatment arm), which could
      lead to the overestimation of treatment effect. AUTHORS' CONCLUSIONS: Additional
      evidence from better, well designed, large-scale trials is needed in order to
      more rigorously evaluate pharmacological interventions for the prevention of
      chronic pain after surgery. Furthermore, available evidence does not support the
      efficacy of gabapentin, pregabalin, non-steroidal anti-inflammatories,
      intravenous steroids, oral NMDA blockers, oral mexiletine, intravenous fentanyl,
      intravenous lidocaine, oral venlafaxine or inhaled nitrous oxide for the
      prevention of chronic postoperative pain.

PMID- 23881792
TI  - Comparative neuroanatomical parcellation of the human and nonhuman primate
      temporal pole.
AB  - The temporal pole is unique to nonhuman and human primates, although other
      species also present temporal cortex. A clear distinction is made between the
      gross anatomical, macroscopic temporal pole, located at the tip of the temporal
      lobe, and the temporal polar cortex, which is a general term that encompasses all
      reported divisions and can be applied to both nonhuman and human primates. In the
      19th century early neuroanatomists identified the temporal polar cortex as a
      different entity, independent from the remainder of the temporal lobe. More
      recently, the temporal polar cortex has been subdivided into different fields.
      The analysis of the different portions that make up the temporal polar cortex was
      first described in the nonhuman primate, and later on in humans. In this review
      we examine the historical course of the concepts about the extension, structure,
      and main cytoarchitectonic areas. The different descriptions are presented in
      chronological order and their relevance is discussed. In general, some common
      features arise in nonhuman and human primates temporopolar cortex, namely, an
      increased thickness of this cortical area, a predominant dysgranular type of
      cortex, and a more restricted extension in humans relative to earlier accounts. A
      common pattern of cytoarchitectonic areas results from the criteria of previous
      authors, although the sulcal anatomy of the human temporal pole has great
      variability. The understanding of the extension, composition, and limits of the
      temporal polar cortex is crucial for identification of separate regions in
      neuroimaging studies. J. Comp. Neurol. 521:4163-4176, 2013. (c) 2013 Wiley
      Periodicals, Inc. 

PMID- 23881793
TI  - Dumbbells, trikes and quads: organic-inorganic hybrid nanoarchitectures based on
      "clicked" gold nanoparticles.
AB  - The controlled assembly of gold nanoparticles in terms of the spatial arrangement
      and number of particles is essential for many future applications like electronic
      devices, sensors and labeling. Here an approach is presented to build up
      oligomers of mono functionalized gold nanoparticles by the use of 1,3-bipolar
      azide alkyne cycloaddition click chemistry. The gold nanoparticles of 1.3 nm
      diameter are stabilized by one dendritic thioether ligand comprising an alkyne
      function. Together with di-, tri- and tetra-azide linker molecules the gold
      nanoparticle can be covalently coupled by a wet chemical protocol. The reaction
      is tracked with IR and UV-vis spectroscopy and the yielded organic-inorganic
      hybrid structures are analyzed by transmission electron microscopy. To evaluate
      the success of this click chemistry reaction statistical analysis of the formed
      oligomers is performed. The geometric and spatial arrangements of the found
      oligomers match perfectly the calculated values for the used linker molecules.
      Dimers, trimers and tetramers could be identified after the reaction with the
      corresponding linker molecule. The results of this model reaction suggest that
      the used click chemistry protocol is working well with mono functionalized gold
      nanoparticles. 

PMID- 23881794
TI  - In vitro fabrication of autologous living tissue-engineered vascular grafts based
      on prenatally harvested ovine amniotic fluid-derived stem cells.
AB  - Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue
      engineering and regenerative medicine. However, before clinical implementation,
      rigorous evaluation of this cell source in clinically relevant animal models
      accepted by regulatory authorities is indispensable. Today, the ovine model
      represents one of the most accepted preclinical animal models, in particular for
      cardiovascular applications. Here, we investigate the isolation and use of
      autologous ovine AFCs as cell source for cardiovascular tissue engineering
      applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and
      from explanted uteri post mortem at different gestational ages (n = 91). Amniotic
      non-allantoic fluid nature was evaluated biochemically and in vivo samples were
      compared with post mortem reference samples. Isolated cells revealed an
      immunohistochemical phenotype similar to ovine bone marrow-derived mesenchymal
      stem cells (MSCs) and showed expression of stem cell factors described for
      embryonic stem cells, such as NANOG and STAT-3. Isolated ovine amniotic fluid
      derived MSCs were screened for numeric chromosomal aberrations and successfully
      differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC
      lineages were then successfully used for the in vitro fabrication of small- and
      large-diameter tissue-engineered vascular grafts (n = 10) and cardiovascular
      patches (n = 34), laying the foundation for the use of this relevant pre-clinical
      in vivo assessment model for future amniotic fluid cell-based therapeutic
      applications.

PMID- 23881795
TI  - Inhaled lead exposure affects tracheal responsiveness and lung inflammation in
      guinea pigs during sensitization.
AB  - Total and differential white blood cells (WBC), and cytokines, levels in serum
      were examined in guinea pigs exposed to inhaled lead acetate. Different groups of
      guinea pigs including: control (group C), sensitized group (group S), and exposed
      animals to aerosol of three lead concentrations during sensitization (n = 6 for
      each group) were studied. Total and differential WBC counts of lung lavage, serum
      cytokine (IFNgamma and IL-4), levels and tracheal responsiveness to methacholine
      and ovalbumin were measured. All measured values were significantly increased
      except for IFNgamma/IL-4 ratio which was significantly decreased in nonexposed
      sensitized and those exposed to all lead concentrations compared to control group
      (p < 0.05 to p < 0.001). Most measured values in animals exposed to higher lead
      concentration were also significantly higher than group S except for tracheal
      responsiveness to methacholine and lymphocyte count. Lead concentration
      significantly increased in lung tissues of animals exposed to all three lead
      concentrations (p < 0.001 for all cases). These results showed that lead exposure
      during sensitization can induce greater increase in tracheal responsiveness,
      total WBC, eosinophil, neutrophil, and basophil counts as well as serum level of
      IL-4. It can also cause a decrease in lymphocyte count, IFNgamma level, and
      IFNgamma/IL-4 ratio especially in its high concentration. Therefore inhaled lead
      exposure may cause increased severity of asthma during development of the
      disease.

PMID- 23881797
TI  - Chemoselectivity control: gold(I)-catalyzed synthesis of 6,7-dihydrobenzofuran
      4(5H)-ones and benzofurans from 1-(alkynyl)-7-oxabicyclo[4.1.0]heptan-2-ones.
AB  - New and chemoselective gold(I)-catalyzed transformations of 1-(arylethynyl)-7
      oxabicyclo[4.1.0]- heptan-2-ones were developed. Two completely different
      products--6,7-dihydrobenzofuran-4(5H)-ones and benzofurans--could be obtained
      from the same starting material. The selectivity is determined by the ligand of
      the gold catalyst: triphenylphosphine delivers 6,7-dihydrobenzofuran-4(5H)-ones,
      and 1,3-bis(diisopropylphenyl)imidazol-2-ylidene leads to benzofurans. Eleven
      examples of each case are provided. The mechanistic suggestions for the pathways
      to both product types are supported by isotope labeling experiments.

PMID- 23881796
TI  - Isoliquiritigenin-induced effects on Nrf2 mediated antioxidant defence in the HL
      60 cell monocytic differentiation.
AB  - To evaluate the role of redox homeostasis in differentiation in human
      promyelocytic leukemia cells (HL-60) induced by isoliquiritigenin (ISL) through
      modulation of the nuclear erythroid-related factor 2/antioxidant responsive
      element (Nrf2/ARE) pathway. Morphological changes, cell surface markers
      CD11b/CD14, and nitroblue tetrazolium (NBT)-reducing ability were used to
      determine the differentiation of HL-60, and 2,7-dichlorofluorescein was used to
      detect the level of intracellular reactive oxygen species (ROS). Thiobarbituric
      acid test was utilised to determine the levels of malondialdehyde production in
      ISL-treated HL-60. The study determines and presents the redox state of the ratio
      of reduced/oxidised glutathione as a consequence of progression from
      differentiation in HL-60. Expression levels of the Nrf2/ARE downstream target
      genes were determined by quantitative polymerase chain reaction. Nicotinamide
      adenine dinucleotide phosphate-oxidase (NADPH oxidase) inhibitors, apocynin
      (APO), and diphenyleneiodonium (DPI) were used for the preliminary study to
      determine the potential downstream targets regulated by NADPH oxidase in ISL
      induced HL-60 differentiation. The data showed a strong dose-response
      relationship between ISL exposure and the characteristics of HL-60
      differentiation, namely, morphology changes, NBT reductive activities, and
      expression levels of surface antigens CD11b/CD14. Intercellular redox homeostasis
      changes toward oxidation during drug exposure are necessary to support ISL
      induced differentiation. The unique expression levels of the Nrf2/ARE downstream
      target genes in the differentiation of HL-60 recorded a statistically significant
      and dose-dependent increase (P < 0.05), which were suppressed by NADPH oxidase
      inhibitor, APO, and DPI. ISL as a differentiation-inducing agent with mechanisms
      involved in the Nrf2/ARE pathway to modulate intercellular redox homeostasis, and
      thus, facilitate differentiation. 

PMID- 23881798
TI  - Black rubber band or yellow latex band for endoscopic variceal ligation: which is
      better?

PMID- 23881800
TI  - The evaluation of haemodynamics in cirrhotic patients with spectral CT.
AB  - OBJECTIVE: To evaluate haemodynamics in cirrhotic patients with portal
      hypertension using spectral CT imaging. METHODS: 118 cirrhotic patients with
      portal hypertension were included in the study group (further divided into Child
      Pugh A, B and C subgroups). The control group consisted of 21 subjects with
      normal liver functionality. All subjects underwent three-phase spectral CT scans.
      Material decomposition images with water and iodine as basis material pairs were
      reconstructed. The iodine concentrations for the hepatic parenchyma in both
      arterial and portal venous phases were measured. The arterial iodine fraction
      (AIF) was obtained by dividing the iodine concentration in the hepatic arterial
      phase by that in the portal venous phase. AIF values from the study and control
      groups were compared using analysis of variance and between subgroups using a
      post-hoc test with Bonferroni correction, with a statistical significance of
      p<0.05. RESULTS: The AIF was 0.25+/-0.05 in the control group, and 0.29+/-0.10,
      0.37+/-0.12 and 0.43+/-0.14 in the study group with Child-Pugh Grades A, B and C,
      respectively. The difference in AIF between the control and study groups was
      statistically significant. The differences were statistically significant between
      the subgroups with multiple comparisons except between the control group and the
      Child-Pugh A group (p=0.685). CONCLUSION: AIF measured in spectral CT could be
      used to evaluate the liver haemodynamics of cirrhotic patients. ADVANCES IN
      KNOWLEDGE: The AIF, provided by spectral CT, could be used as a new parameter to
      observe liver haemodynamics.

PMID- 23881803
TI  - Long-term results of electrical stimulation of the lower esophageal sphincter for
      the treatment of gastroesophageal reflux disease.
AB  - BACKGROUND AND STUDY AIMS: In patients with gastroesophageal reflux disease
      (GERD), temporary electrical stimulation of the lower esophageal sphincter (LES)
      increases LES pressure without interference with LES relaxation. The aim of the
      current study was to investigate the safety and efficacy of long term LES
      electrical stimulation therapy (LES-EST), using a permanently implanted
      stimulator for the treatment of GERD. PATIENTS AND METHODS: Patients with GERD
      who were at least partially responsive to proton pump inhibitors (PPIs) and who
      had hiatal hernia of <= 3 cm and esophagitis of Los Angeles Grade A, B, or C were
      included in the study. Stimulation electrodes were placed in the LES and a pulse
      generator (EndoStim LES Stimulation System; EndoStim BV, The Hague, The
      Netherlands) was implanted laparoscopically. LES stimulation was delivered at 20
      Hz, 215 MUs, 3 - 8 mA in multiple 30-minute sessions. Patients were evaluated at
      follow-up using the GERD Health-Related Quality of Life (HRQL) questionnaire,
      daily symptom and medication diaries, the SF-12 Health Survey, esophageal pH
      testing, and high resolution manometry. RESULTS: A total of 24 patients (mean age
      53 +/- 12 years; 14 men) were implanted and 23 completed the 12-month evaluation.
      No serious implantation or stimulation-related adverse affects or sensations were
      reported. Median composite GERD-HRQL score at 12 months was 2.0 (interquartile
      range [IQR] 0 - 3.0), which was significantly better than baseline scores both on
      PPI therapy (median 9.0, IQR 6.0 - 10.0; P = 0.002) and off PPIs (median 23.5,
      IQR 21 - 25.75; P < 0.001). The median percentage of the 24-hour period with
      esophageal pH < 4.0 at baseline was 10.1 % (IQR 7.7 - 15.5), which was reduced to
      3.3 % (1.8 - 6.9) at 12 months (P < 0.001), with 69 % of patients showing either
      normalization or > 50 % improvement in their distal esophageal pH. At 12 months,
      96 % of patients (22/23) were completely off PPI medication. CONCLUSION: During
      the long term follow-up of 12 months, LES - EST was safe and effective for the
      treatment of GERD. There was a significant and sustained improvement in GERD
      symptoms, reduction in esophageal acid exposure with elimination of daily PPI
      usage, and no stimulation-related adverse effects.

PMID- 23881799
TI  - A novel reporter system for molecular imaging and high-throughput screening of
      anticancer drugs.
AB  - Apoptosis is irreversible programmed cell death, characterized by a cellular
      cascade activation of caspase 3, which subsequently degrades proteins and other
      components of cells with a motif sequence. Here we report a novel reporter system
      to detect apoptosis, growth arrest, and cell death based on controlled and self
      amplified protein degradation. The key element of the reporter system is an
      apoptotic sensor chimerical protein which consists of three components:
      procaspase 3, ubiquitin (Ub), and a strong consensus sequence of N-degron.
      Between each of these units is a DEVD (Asp-Glu-Val-Asp) sequence, which acts as
      the cleavage target of caspase 3. This non-conventional signal loss approach is
      much more sensitive than other native methods that are based on signal gain. The
      superior sensitivity is demonstrated by its effective application in 386-well
      high-throughput screening (HTS) with low drug concentrations and a short
      incubation time. The HTS selection process using this reporter system is very
      simple and economic. The simplicity eliminates potential errors introduced by
      multiple steps; there is no need for any substrate. Furthermore, the cells in the
      assay need not be disrupted, and the morphology of the cells can provide
      additional information on mechanisms. After HTS, the intact cells can also be
      used for other analytic analysis. This system thus has a potentially important
      role in the discovery and development of new anticancer drugs. It also appears to
      be very versatile, can be used both in vitro and in vivo with different linked
      reporter genes, and can be used for a variety of imaging applications. 

PMID- 23881804
TI  - Risk of gastric or peritoneal recurrence, and long-term outcomes, following
      pancreatic cancer resection with preoperative endosonographically guided fine
      needle aspiration.
AB  - BACKGROUND AND STUDY AIMS: There have been concerns regarding tumor cell seeding
      along the needle track or within the peritoneum caused by preoperative endoscopic
      ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to
      evaluate whether preoperative EUS-FNA is associated with increased risk of
      stomach/peritoneal recurrence and whether the procedure affects long term
      survival. METHODS: The records of patients diagnosed with malignant solid and
      cystic pancreatic neoplasms who underwent surgery with curative intent between
      1996 and 2012 were reviewed. RESULTS: A total of 256 patients with similar
      baseline characteristics were included: 48 patients in the non-EUS-FNA group and
      208 in the EUS-FNA group. Recurrence data were available for 207 patients. Median
      length of follow-up was 23 months (range 0 - 111 months). A total of 19 patients
      had gastric or peritoneal recurrence; 6 (15.4 %) in the non-EUS-FNA group vs. 13
      (7.7 %) in the EUS-FNA group (P = 0.21). Three patients had recurrence in the
      stomach wall: one (2.6 %) patient in the non-EUS-FNA group vs. two patients (1.2
      %) in EUS-FNA group (P = 0.46). A total of 16 patients had peritoneal recurrence:
      5 patients (12.8 %) in the non-EUS-FNA group and 11 patients (6.5 %) in the EUS
      FNA group (P = 0.19). In a multivariate analysis, undergoing EUS-FNA was not
      associated with increased cancer recurrence or decreased overall survival.
      CONCLUSION: Pre-operative EUS-FNA was not associated with an increased rate of
      gastric or peritoneal cancer recurrence in patients with resected pancreatic
      cancer. Two patients had gastric wall recurrence following the procedure, but
      this may be explained by direct tumor extension. This suggests that EUS-FNA is
      not associated with an increased risk of needle track seeding.

PMID- 23881805
TI  - New flexible endoscopic full-thickness suturing device: a triple-arm-bar suturing
      system.
AB  - BACKGROUND AND STUDY AIM: A reliable full-thickness suturing device is necessary
      for pure natural orifice transluminal endoscopic surgery (NOTES). The present
      study focused on assessing the reliability of a new suturing device. METHODS: A
      total of 60 single sutures were tested to close 5-cm incisions in 8-cm square
      pieces of resected swine stomach. Each incision was sutured by an over-the-scope
      clip (OTSC; n = 20), a single hand-sewn stitch (n = 20), or a single triple-arm
      bar suturing system (TBSS) stitch. The maximum pulling force durability (MPD) of
      each suture was tested. To assess the reliability of the TBSS for endoscopic full
      thickness resection (EFTR), 60 EFTRs of 50 mm diameter were performed on excised
      swine stomachs. After EFTR, full-thickness sutures were made using 3-stitch OTSCs
      (n = 20), 10-stitch hand-sewn sutures (n = 20), or 10-stitch TBSS sutures (n =
      20). Outcomes were the MPD test for both single stitch and multiple stitch
      applications and the suturing time for single-stitch sutures. RESULTS: In the
      single-stitch MPD tests, there were significant differences between OTSCs and
      hand-sewn sutures (P = 0.0002) and between OTSCs and TBSS sutures (P = 0.0001),
      but no significant difference between hand-sewn and TBSS sutures. The multiple
      stitch sutures revealed significant differences between OTSCs and hand-sewn
      sutures (P = 0.0039), and between OTSCs and TBSS sutures (P = 0.013). There was
      no significant difference between hand-sewn and TBSS sutures. There were
      significant differences in suture times between OTSC, hand-sewn sutures, and TBSS
      sutures (P < 0.05). CONCLUSIONS: Both single-stitch and multiple-stitch sutures
      using TBSS have similar strength to hand-sewn sutures. TBSS is a reliable
      suturing device.

PMID- 23881806
TI  - A simple novel endoscopic successive suture device: a validation study for
      closure strength and reproducibility.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic surgical technology has been developing
      rapidly. Although several successful endoscopic closure devices have already been
      introduced, only a few of them have demonstrated improvements in closure strength
      and reproducibility over conventional endoscopic clip closures or hand sutures.
      The objective of this study was to test the feasibility of a novel successive
      suturing device (SSD) by measuring closure strength and reproducibility. MATERIAL
      AND METHODS: Porcine stomach models were used in this study. Endoclips, full
      thickness hand sutures, and the novel SSD sutures were used to close a
      perforation in the stomach wall, with 10 stomachs being tested for each closure
      method. Endoclips and SSD sutures were performed using a two-channel endoscope,
      and the hand sutures were performed from outside of the stomach wall. Air leakage
      pressure was measured to determine the closure strength and reproducibility of
      each method. RESULTS: The mean air leakage pressure of the SSD closure was 62.7
      +/- 8.2 mmHg. SSD-treated stomachs exhibited significantly greater air leakage
      pressure than Endoclip-treated stomachs. The standard deviation of bursting
      pressure in SSD stomachs was found to be significantly smaller than that of hand
      sewn stomachs but was not different from that of Endoclip stomachs. CONCLUSIONS:
      The consistent closure strength of SSD stomachs demonstrated the reliability and
      reproducibility of this new closure method. These promising results in closure
      strength and reproducibility suggest the feasibility of the proposed device for
      clinical applications.

PMID- 23881807
TI  - Single-session ERCP in patients with previous Roux-en-Y gastric bypass using
      percutaneous-assisted transprosthetic endoscopic therapy: a case series.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) remains technically
      challenging following Roux-en-Y gastric bypass (RYGB). Various techniques have
      been described to access the excluded stomach. We describe our experience using
      percutaneous-assisted transprosthetic endoscopic therapy (PATENT) to perform
      antegrade ERCP. Balloon enteroscopy was used to access the excluded stomach.
      Direct retrograde percutaneous endoscopic gastrostomy (RPEG) was performed and an
      esophageal self-expandable metal stent (SEMS) was deployed within the gastrostomy
      tract. A duodenoscope was advanced through the SEMS and antegrade ERCP was
      performed. Following ERCP, a gastrostomy tube was placed through the SEMS to
      maintain patency. Five patients underwent successful antegrade ERCP using PATENT.
      All patients had a diagnosis of sphincter of Oddi dysfunction. Biliary
      sphincterotomy was performed in all patients and liver enzymes normalized in four
      patients with preprocedural elevations. In conclusion, antegrade ERCP employing
      PATENT is feasible and can be performed during a single endoscopic session in
      patients with previous RYGB. 

PMID- 23881808
TI  - Closing the gap in POEM.

PMID- 23881809
TI  - Gastrointestinal varicella zoster infection. Dissemination or reactivation of a
      latent virus in the gut?

PMID- 23881810
TI  - Reply to Dado et al.

PMID- 23881811
TI  - Electrosurgical hot biopsy forceps coagulation: more (intensity) is less
      (complications).

PMID- 23881812
TI  - Are selective serotonin reuptake inhibitors (SSRIs) a risk factor for post
      polypectomy bleeding?

PMID- 23881814
TI  - Prognostic value of access and non-access sites bleeding after percutaneous
      coronary intervention.
AB  - BACKGROUND: Little is known about the impact of bleeding site on mortality after
      percutaneous coronary intervention. The aim of this study was to assess the
      impact of access and non-access site bleeding within 30 days after percutaneous
      coronary intervention on mortality. METHODS AND RESULTS: This study represents a
      pooled patient-level analysis of 14 180 patients recruited in 7 randomized
      trials. Access and non-access site bleeding were assessed using the Bleeding
      Academic Research Consortium criteria. The primary outcome was 1-year mortality.
      Follow-up was complete in 97.5% of the patients. There were 414 deaths within the
      first year after percutaneous coronary intervention: 44 deaths among patients
      with access site bleeding, 60 deaths among patients with non-access site
      bleeding, and 310 deaths among patients without bleeding (Kaplan-Meier estimates
      of mortality, 4.5%, 10.0%, and 2.5%, respectively; adjusted hazard ratio, 1.72
      [95% confidence interval, 1.19-2.47] for access site bleeding versus no bleeding;
      hazard ratio, 2.78 [2.00-3.86] for non-access site versus no bleeding). The
      inclusion of non-access site bleeding (the absolute and relative integrated
      discrimination improvement, 0.005 and 8.9%; P=0.031) but not of access site
      bleeding (the absolute and relative integrated discrimination improvement, 0.0015
      and 2.7%; P=0.084) was associated with an improvement of the discriminatory power
      of multivariable model for mortality prediction. CONCLUSIONS: Both access and non
      access site bleeding events occurring within 30 days of a percutaneous coronary
      intervention are independently associated with an increased risk of 1-year
      mortality. Non-access site bleeding is a stronger correlate of mortality than
      access site bleeding, and it improves the discriminatory power of models for
      mortality prediction.

PMID- 23881815
TI  - Controlled reperfusion versus conventional treatment of the acutely ischemic
      limb: results of a randomized, open-label, multicenter trial.
AB  - BACKGROUND: Amputation rates and mortality in patients with severe acute limb
      ischemia remain high. The protective effect of controlled reperfusion (CR) on
      tissue damage because of local and systemic reperfusion injury is unclear.
      METHODS AND RESULTS: A total of 174 patients from 14 centers were randomized
      between conventional treatment (CT) by thrombembolectomy and normal blood
      reperfusion and thrombembolectomy followed by CR. The primary end point was
      amputation-free survival (AFS) after 4 weeks (CT, 82.4%; CR, 82.6%). Secondary
      end points were AFS (CT, 62.4%; CR, 63.1%) and overall survival (CT, 71.6%; CR,
      76.3%) after 1 year. Analysis of the prognostic effects of preoperative factors
      revealed a strong adverse effect of bilateral involvement on AFS. In the subgroup
      with unilateral ischemia (n=160), age >80 years and central localization of the
      occlusion had independent negative prognostic effects on AFS. In the per-protocol
      population of 104 patients with unilateral ischemia, treatment per protocol, and
      successful revascularization, amputation or death within 4 weeks occurred in only
      8% as compared with 33% in patients not fulfilling these criteria. No differences
      between treatment groups CT and CR were found, neither overall nor in the per
      protocol population nor in patient subgroups defined by other pre- and
      intraoperative factors. CONCLUSIONS: Similar AFS in patients with CT or with CR
      was observed in this large randomized multicenter trial. CLINICAL TRIAL
      REGISTRATION URL: http://www.drks.de. Unique identifier: DRKS00000579.

PMID- 23881816
TI  - Cell sheet engineering and its application for periodontal regeneration.
AB  - Periodontitis is a inflammation induced by a bacterial infection that causes the
      destruction of the attachment apparatus of dental roots. Several materials, such
      as bone graft materials, barrier membranes and protein products have been
      developed and used to treat periodontal defects clinically; however, it is
      difficult to regenerate the complete periodontal tissue structure. Recently,
      cytotherapeutic approaches have been introduced to overcome the limitation of
      conventional procedures. The in vitro-expanded autologous cells derived from
      several kinds of tissues have already been used in several clinical trials. These
      cytotherapeutic treatments have been shown to be safe and effective for the
      treatment of periodontitis. Our strategy has been to integrate stem cell biology
      and cell sheet engineering, in which a temperature-responsive intelligent polymer
      is grafted onto the surface of cell culture dish to create a 'cell sheet', to
      achieve a novel treatment method for periodontitis. By simple reduction of the
      temperature to below 32 degrees C, a contiguous cell sheet, which is capable of
      keeping extracellular matrix proteins and cell-cell interactions intact, can be
      harvested for transplantation without the use of scaffolds. This technology has
      already been employed in clinical trials, confirming the safety and efficacy of
      the treatment. In this review, we introduce recent progress in the engineering of
      cell sheets and review the potential of cell sheet technology for periodontal
      regenerative medicine.

PMID- 23881817
TI  - Biochips for cell biology by combined dip-pen nanolithography and DNA-directed
      protein immobilization.
AB  - A general methodology for patterning of multiple protein ligands with lateral
      dimensions below those of single cells is described. It employs dip pen
      nanolithography (DPN) patterning of DNA oligonucleotides which are then used as
      capture strands for DNA-directed immobilization (DDI) of oligonucleotide-tagged
      proteins. This study reports the development and optimization of PEG-based liquid
      ink, used as carrier for the immobilization of alkylamino-labeled DNA oligomers
      on chemically activated glass surfaces. The resulting DNA arrays have typical
      spot sizes of 4-5 MUm with a pitch of 12 MUm micrometer. It is demonstrated that
      the arrays can be further functionalized with covalent DNA-streptavidin (DNA-STV)
      conjugates bearing ligands recognized by cells. To this end, biotinylated
      epidermal growth factor (EGF) is coupled to the DNA-STV conjugates, the resulting
      constructs are hybridized with the DNA arrays and the resulting surfaces used for
      the culturing of MCF-7 (human breast adenocarcinoma) cells. Owing to the lateral
      diffusion of transmembrane proteins in the cell's plasma membrane, specific
      recruitment and concentration of EGF receptor can be induced specifically at the
      sites where the ligands are bound on the solid substrate. This is a clear
      demonstration that this method is suitable for precise functional manipulations
      of subcellular areas within living cells. 

PMID- 23881819
TI  - Assembly and stepwise oxidation of interpenetrated coordination cages based on
      phenothiazine.
AB  - A breath of fresh air is sufficient for the eightfold S-monooxygenation of an
      interpenetrated double cage based on eight phenothiazine ligands and four square
      planar-coordinated Pd(II) cations. Besides these two cages, which were both
      characterized by X-ray crystallography, an eightfold S-dioxygenated double-cage
      was obtained under harsher oxidation conditions.

PMID- 23881818
TI  - Medial temporal cortices in ex vivo magnetic resonance imaging.
AB  - This review focuses on the ex vivo magnetic resonance imaging (MRI) modeling of
      medial temporal cortices and associated structures, the entorhinal verrucae and
      the perforant pathway. Typical in vivo MRI has limited resolution due to
      constraints on scan times and does not show laminae in the medial temporal lobe.
      Recent studies using ex vivo MRI have demonstrated lamina in the entorhinal,
      perirhinal, and hippocampal cortices. These studies have enabled probabilistic
      brain mapping that is based on the ex vivo MRI contrast, validated to histology,
      and subsequently mapped onto an in vivo spherically warped surface model.
      Probabilistic maps are applicable to other in vivo studies.

PMID- 23881821
TI  - High CO2-capture ability of a porous organic polymer bifunctionalized with
      carboxy and triazole groups.
AB  - A new porous organic polymer, SNU-C1, incorporating two different CO2 -attracting
      groups, namely, carboxy and triazole groups, has been synthesized. By activating
      SNU-C1 with two different methods, vacuum drying and supercritical-CO2 treatment,
      the guest-free phases, SNU-C1-va and SNU-C1-sca, respectively, were obtained.
      Brunauer-Emmett-Teller (BET) surface areas of SNU-C1-va and SNU-C1-sca are 595
      and 830 m(2) g(-1), respectively, as estimated by the N2-adsorption isotherms at
      77 K. At 298 K and 1 atm, SNU-C1-va and SNU-C1-sca show high CO2 uptakes, 2.31
      mmol  g(-1) and 3.14 mmol  g(-1), respectively, the high level being due to the
      presence of abundant polar groups (carboxy and triazole) exposed on the pore
      surfaces. Five separation parameters for flue gas and landfill gas in vacuum
      swing adsorption were calculated from single-component gas-sorption isotherms by
      using the ideal adsorbed solution theory (IAST). The data reveal excellent CO2
      separation abilities of SNU-C1-va and SNU-C1-sca, namely high CO2-uptake
      capacity, high selectivity, and high regenerability. The gas-cycling experiments
      for the materials and the water-treated samples, experiments that involved
      treating the samples with a CO2-N2 gas mixture (15:85, v/v) followed by a pure N2
      purge, further verified the high regenerability and water stability. The results
      suggest that these materials have great potential applications in CO2 separation.

PMID- 23881820
TI  - Examining cultural factors that influence treatment decisions: a pilot study of
      Latino men with cancer.
AB  - The objective of this study was to explore beliefs and treatment decisions of
      foreign-born Latino men from Cuba, Mexico, Colombia, and Venezuela, who have been
      diagnosed with cancer and who live in Central Florida, USA. Experiences related
      to knowledge of diagnosis, treatment decisions, communication with health
      providers, family involvement, and advance care planning (ACP) discussions
      following the diagnosis of cancer are central to this study. This study used
      qualitative in-depth semi-structured interviews and thematic analysis. The
      interviews were conducted with 15 Latino men who have been diagnosed with cancer
      within the past 5 years and who reside in the community. The interviews were
      conducted and transcribed in Spanish and then translated into English. The median
      age was 55.4 years. Nine Latino men had prostate cancer, two had brain cancer,
      two had colorectal cancer, and two had lung cancer. Emerging themes involved the
      suddenness of the diagnosis, fear of dying, expectations of diagnosis-related
      communication, reliance on physicians for treatment decisions, limited
      information pertaining to ACP, family support, and role changes. Latino men's
      limited knowledge of cancer diagnosis and treatment options coupled with their
      fear led them to immediately believe that they were going to die. Knowledge gaps
      regarding diagnosis-related communication, treatment decisions, and ACP varied
      among the men. The forthright diagnosis communication and the expectation to
      engage in decision making are contrary to Latinos men's beliefs of reliance on
      health providers decisions. The findings contribute to understanding Latino men's
      beliefs about a cancer diagnosis and treatment decisions.

PMID- 23881822
TI  - The topology, in model membranes, of the core peptide derived from the T-cell
      receptor transmembrane domain.
AB  - The T-cell receptor-CD3 complex (TCR-CD3) serves a critical role in protecting
      organisms from infectious agents. The TCR is a heterodimer composed of alpha- and
      beta-chains, which are responsible for antigen recognition. Within the
      transmembrane domain of the alpha-subunit, a region has been identified to be
      crucial for the assembly and function of the TCR. This region, termed core
      peptide (CP), consists of nine amino acids (GLRILLLKV), two of which are charged
      (lysine and arginine) and are crucial for the interaction with CD3. Earlier
      studies have shown that a synthetic peptide corresponding to the CP sequence can
      suppress the immune response in animal models of T-cell-mediated inflammation, by
      disrupting proper assembly of the TCR. As a step towards the understanding of the
      source of the CP activity, we focused on CP in egg
      phosphatidylcholine/cholesterol (9:1, mol/mol) model membranes and determined its
      secondary structure, oligomerization state, and orientation with respect to the
      membrane. To achieve this goal, 15-residue segments of TCRalpha, containing the
      CP, were synthesized and spin-labeled at different locations with a nitroxide
      derivative. Electron spin-echo envelope modulation spectroscopy was used to probe
      the position and orientation of the peptides within the membrane, and double
      electron-electron resonance measurements were used to probe its conformation and
      oligomerization state. We found that the peptide is predominantly helical in a
      membrane environment and tends to form oligomers (mostly dimers) that are
      parallel to the membrane plane. 

PMID- 23881823
TI  - Characterization of the components of urban particulate matter mediating
      impairment of nitric oxide-dependent relaxation in intrapulmonary arteries.
AB  - We have previously shown that exposure to urban particulate matter (UPM) impairs
      endothelial nitric oxide (NO) bioactivity in intrapulmonary arteries. As UPM is
      composed of heterogeneous constituents, the aim of this study was to clarify the
      class of pollutants responsible for such effect. Extracts (aqueous, acidic or
      organic) were prepared from SRM1648, an UPM sample collected in St. Louis (MO,
      USA). The metal composition of extracts as well as endotoxin content was
      determined. The effects of each extract, metal mixture and endotoxin were
      evaluated on endothelium-dependent relaxation to acetylcholine (reflecting
      endothelial NO production) in rat isolated intrapulmonary arteries. Aqueous or
      organic SRM1648 pretreatment altered acetylcholine-induced relaxation, similar to
      that induced by native SRM1648. Organic extract induced similar attenuation of
      acetylcholine relaxation than organic-treated SRM1648, whereas aqueous extract
      had no effect. Acidic pretreatment, which impoverished metal and endotoxin
      content of SRM1648, prevented the impairment of acetylcholine-induced relaxation.
      However, neither the acidic extract enriched in metals, nor a metal mixture
      representative of SRM1648 content, modified acetylcholine relaxation, while
      endotoxin impaired it. Polymyxin B, which chelates endotoxin, prevented SRM1648
      induced decrease in relaxation to acetylcholine. It is concluded that SRM1648
      induced impairment of endothelial NO-dependent relaxation in intrapulmonary
      arteries unlikely involved a soluble factor released by vascular cells during UPM
      exposure, but rather an organic extractible and acidic-sensitive constituents of
      UPM. Endotoxin, but not metals, may be responsible for UPM-induced impairment of
      endothelial NO-dependent relaxation.

PMID- 23881828
TI  - Design of polyethylene glycol-polyethylenimine nanocomplexes as non-viral
      carriers: mir-150 delivery to chronic myeloid leukemia cells.
AB  - MicroRNAs (miRNAs) are acknowledged as indispensable regulators relevant in many
      biological processes, and they have been pioneered as therapeutic targets for
      curing disease. miRNAs are single-stranded, small (19-22 nt) regulatory non
      coding RNAs whose deregulation of expression triggers human cancers, including
      leukemias, mainly through dysregulation of expression of leukemia genes. miRNAs
      can function as tumour suppressors (suppressing malignant potential) or oncogenes
      (activating malignant potential) like actors of complex diseases. To address the
      issue of overcoming instability and low transfection efficiency in vitro, the
      polyethylene glycol-polyethyleneimine (PEG-PEI) nanoparticle was used as non
      viral vector carrier for miR-150 transfection, which is downregulated in chronic
      myeloid leukemia. PEG-PEI [PEG(550)3 -g-PEI(1800) ]/miRNA nanocomplexes were
      synthesised and characterised by particle size distribution (PSD), polydispersity
      index (PDI) and zeta potential, surface charge, their cytotoxicity, and
      transfection efficiency. Interaction with human leukemia cells (K-562 and KU812)
      and control cells NCI-BL2347 with them has been investigated. The transfection
      efficiency of PEG-PEI/miRNA at N/P 26 rose 6.7-fold above the control by qRT-PCR.
      The size of homogenous nanocomplexes (PBI < 0.5) was 160.8 +/- 11 nm. The data
      indicate that PEG-PEI may be an encouraging non-viral carrier for altering miRNA
      expression in the treatment of chronic myeloid leukemia, with many advantages
      such as relatively high miRNA transfection efficiency and low cytotoxicity. 

PMID- 23881832
TI  - Dependence of macrophage superoxide release on the pulse amplitude of an applied
      pressure regime: a potential factor at the soft tissue-implant interface.
AB  - Failure of soft tissue implants has been largely attributed to the influence of
      biomaterial surface properties on the foreign body response, but some implant
      complications, e.g. macrophage accumulation and necrosis, are still not
      effectively addressed with surface treatments to minimize deleterious biomaterial
      effects. We explored an alternative explanation for implant failure, linking
      biocompatibility with implant micromotion-induced pressure fluctuations at the
      tissue-biomaterial interface. For this purpose, we used a custom in vitro system
      to characterize the effects of pressure fluctuations on the activity of
      macrophages, the predominant cells at a healing implant site. Initially, we
      quantified superoxide production by HL60-derived macrophage-like cells under
      several different pressure regimes with means of 5-40 mmHg, amplitudes of 0-15
      mmHg and frequencies of 0-1.5 Hz. All pressure regimes tested elicited
      significantly (p < 0.05) reduced superoxide production by macrophage-like cells
      relative to parallel controls. Notably, pressure-sensitive reductions in
      superoxide release correlated (r(2)  = 0.74; p < 0.01) only with pulse pressures.
      Based on the connection between superoxide production and cell viability, we also
      explored the influence of cyclic pressure on macrophage numbers and death.
      Compared to controls, adherent macrophage-like cells exposed to 7.5/2.5 mmHg
      cyclic pressures for 6 h exhibited significantly (p < 0.01) reduced cell numbers,
      independent of cell death. A similar effect was observed for cells treated with
      10 U/ml superoxide dismutase. Collectively, our results suggest that pressure
      pulses are a putative regulator of macrophage adhesion via a superoxide-related
      effect. Pressure fluctuations, e.g. due to implant micromotion, may, therefore,
      potentially modulate macrophage-dependent wound healing.

PMID- 23881833
TI  - A directly linked ferrocene-naphthalenediimide conjugate: precise control of
      stacking structures of pi-systems by redox stimuli.

PMID- 23881835
TI  - Electrical biomolecule detection using nanopatterned silicon via block copolymer
      lithography.
AB  - An electrical biosensor exploiting a nanostructured semiconductor is a promising
      technology for the highly sensitive, label-free detection of biomolecules via a
      straightforward electronic signal. The facile and scalable production of a
      nanopatterned electrical silicon biosensor by block copolymer (BCP) nano
      lithography is reported. A cost-effective and large-area nanofabrication, based
      on BCP self-assembly and single-step dry etching, is developed for the hexagonal
      nanohole patterning of thin silicon films. The resultant nanopatterned electrical
      channel modified with biotin molecules successfully detects the two proteins,
      streptavidin and avidin, down to nanoscale molarities (~1 nm). The nanoscale
      pattern comparable to the Debye screening length and the large surface area of
      the three-dimensional silicon nanochannel enable excellent sensitivity and
      stability. A device simulation confirms that the nanopatterned structure used in
      this work is effective for biomolecule detection. This approach relying on the
      scalable self-assembly principle offers a high-throughput manufacturing process
      for clinical lab-on-a-chip diagnoses and relevant biomolecular studies.

PMID- 23881834
TI  - Learning in Alzheimer's disease is facilitated by social interaction.
AB  - Seminal work in Gary Van Hoesen's laboratory at Iowa in the early 1980s
      established that the hallmark neuropathology of Alzheimer's disease (AD;
      neurofibrillary tangles) had its first foothold in specific parts of the
      hippocampal formation and entorhinal cortex, effectively isolating the
      hippocampus from much of its input and output and causing the distinctive
      impairment of new learning that is the leading early characteristic of the
      disease (Hyman et al., 1984). The boundaries and conditions of the anterograde
      memory defect in patients with AD have been a topic of intense research interest
      ever since (e.g., Graham and Hodges, 1977; Nestor et al., 2006). For example, it
      has been shown that patients with AD may acquire some new semantic information
      through methods such as errorless learning, but learning under these conditions
      is typically slow and inefficient. Drawing on a learning paradigm (a
      collaborative referencing task) that was previously shown to induce robust and
      enduring learning in patients with hippocampal amnesia, we investigated whether
      this task would be effective in promoting new learning in patients with AD. We
      studied five women with early-stage AD and 10 demographically matched healthy
      comparison participants, each interacting with a familiar communication partner.
      AD pairs displayed significant and enduring learning across trials, with
      increased accuracy and decreased time to complete trials, in a manner
      indistinguishable from healthy comparison pairs, resulting in efficient and
      economical communication. The observed learning here most likely draws on neural
      resources outside the medial temporal lobes. These interactive communication
      sessions provide a potent learning environment with significant implications for
      memory intervention.

PMID- 23881836
TI  - Intermolecular spin relaxation and translation diffusion in liquids and polymer
      melts: insight from field-cycling 1H NMR relaxometry.
AB  - With the advent of commercial field-cycling (FC) spectrometers, NMR relaxometry
      has gained new momentum as a method of investigating dynamics in liquids and
      polymers. The outcome of FC NMR experiments is spin-lattice relaxation time
      versus frequency (relaxation dispersion). In the case of protons, due to the
      intra- and intermolecular origin of dipolar interactions, the relaxation
      dispersion reflects rotational as well as translational dynamics. The latter
      shows a universal dispersion law at low frequencies, which allows determination
      of the diffusion coefficient D(T) in addition to the rotational correlation time
      tau(rot)(T), that is, FC (1)H NMR becomes an alternative to field-gradient NMR
      spectroscopy. Subdiffusive translation found in polymers can be accessed by
      singling out the intermolecular relaxation through isotope dilution experiments,
      and the mean square displacement can then be revealed as a function of time, thus
      complementing neutron scattering experiments. Likewise, information on
      reorientational dynamics is provided by the intramolecular relaxation. Assuming
      frequency-temperature superposition the corresponding correlation functions can
      be monitored up to eight decades in amplitude and time, which allows thorough
      testing of current polymer theories.

PMID- 23881837
TI  - Parental programming: how can we improve study design to discern the molecular
      mechanisms?
AB  - The contribution of inherited non-genetic factors to complex diseases is of great
      current interest. The ways in which mothers and fathers can affect their
      offspring's health clearly differ as a result of the intimate interactions
      between mother and offspring during pre- and postnatal life. There is, however,
      potential for some overlap in mechanisms, particularly epigenetic mechanisms. A
      small number of epidemiological studies and animal models have investigated the
      non-genetic contribution of the parents to offspring health. Discovering new
      mechanisms of disease inheritance is technically difficult, especially in
      genetically, socially and environmentally heterogeneous human populations.
      Therefore, rigorous experimental design, appropriate sample numbers and the use
      of high-throughput technologies are necessary to provide convincing evidence.
      Based on recent examples from the literature, here we propose several ways to
      improve human studies that aim to identify the underlying mechanisms of
      transgenerational inheritance of metabolic disease.

PMID- 23881838
TI  - Regioselective C2 Oxidative Olefination of Indoles and Pyrroles through Cationic
      Rhodium(III)-Catalyzed C-H Bond Activation.
AB  - Be economic with your atoms! An efficient Rh-catalyzed oxidative olefination of
      indoles and pyrroles with broad substrate scope and tolerance is reported. The
      catalytic reaction proceeds with excellent regio- and stereoselectivity. The
      directing group N,N-dimethylcarbamoyl was crucial for the reaction and could be
      removed easily. 

PMID- 23881839
TI  - Study of DNA synthesis and mitotic activity of hepatocytes and its relation to
      angiogenesis in hepatectomised tumour bearing mice.
AB  - Partial hepatectomy (PH) alters serum concentrations of substances involved in
      cellular proliferation, leading to the compensatory liver hyperplasia.
      Furthermore, angiogenesis is mainly stimulated by vascular endothelial growth
      factor (VEGF) and is a fundamental requirement either in liver regeneration or in
      tumours growth. This study looks at the expression of VEGF, DNA synthesis (DNAs)
      and mitotic activity (MA) in hepatectomised (H) and hepatectomised-tumour bearing
      (HTB) mice throughout a 24 h period. Adult male mice were sacrificed every 4 h
      from 26 to 50 h post-hepatectomy. H mice show a circadian rhythm in VEGF
      expression with a maximum value of 2.6 +/- 0.1 at 08/46 h of day/hours
      posthepatectomy (HD/HPH); in DNAs, the maximum value was 3.4 +/- 0.3 at 16/30
      (HD/HPH) and in MA it was 2.3 +/- 0.01 at 12/50 (HD/HPH). In HTB animals the peak
      of VEGF expression appears at 16/30 (HD/HPH) with a maximum value of 3.7 +/- 0.1,
      the peak of DNAs was at 00/38 (HD/HPH) with a value of 4.6 +/- 0.3 and the
      maximum value of MA of 08/46 (HD/HPH) with a value of 3.01 +/- 0.3. We can
      conclude that the presence of the tumour induces modifications in the intensity
      and the temporal distribution of the circadian curves of VEGF expression, DNAs
      and MA of hepatectomised animals. 

PMID- 23881841
TI  - Responsive photonic hydrogels based on nanocrystalline cellulose.

PMID- 23881840
TI  - Triage of women with minor abnormal cervical cytology: meta-analysis of the
      accuracy of an assay targeting messenger ribonucleic acid of 5 high-risk human
      papillomavirus types.
AB  - BACKGROUND: High-risk human papillomavirus (hrHPV) DNA detection is generally
      accepted for the triage of women with a cytologic diagnosis of atypical squamous
      cells of undetermined significance (ASC-US). However, no consensus has been
      reached on the optimal management of low-grade squamous intraepithelial lesions
      (LSIL). METHODS: In this meta-analysis, the diagnostic accuracy of nucleic acid
      sequence-based amplification (NASBA) detection of messenger ribonucleic acid
      (mRNA) of 5 hrHPV types (the PreTect HPV-Proofer and NucliSENS EasyQ tests) for
      detecting grade 2 cervical intraepithelial neoplasia or worse (CIN2+) and CIN3+
      was assessed in women who had a diagnosis of ASC-US and LSIL. The results were
      compared with the Hybrid Capture-2 (HC2) assay, which detects the DNA of 13 hrHPV
      types. A bivariate random-effect model that incorporated the intrinsic
      correlation between the true-positive and false-positive rates was used for a
      pooled meta-analysis. RESULTS: Considering underlying CIN2+, the pooled absolute
      sensitivity of the 10 included studies was 75.4% (95% confidence interval [CI],
      68.1%-82.7%) and 76.2% (95% CI, 68.3%-76.9%) for the triage of ASC-US and LSIL,
      respectively. The pooled absolute specificity to exclude CIN2+ was 77.9% (95% CI,
      70.1%-85.7%) and 74.2% (95% CI, 69.5%-78.8%) in women with ASC-US and LSIL,
      respectively. Five studies allowed direct comparison of the mRNA assays with HC2.
      Considering CIN2+ in women with ASC-US and LSIL, mRNA testing was substantially
      more specific than the HC2 assay (ratio: 1.98 and 3.36, respectively; P < .001)
      but was less sensitive (ratio: 0.80 and 0.74, respectively; P < .001).
      CONCLUSIONS: HPV assays for detecting the mRNA of 5 hrHPV types may reduce the
      over-diagnosis of women who have minor cytologic abnormalities. However, given
      the lower sensitivity, women with negative mRNA test results cannot be considered
      free of CIN2+ and require further surveillance.

PMID- 23881842
TI  - Void coalescence in core/alloy nanoparticles with stainless interfaces.
AB  - The oxidation properties of nanoparticles with core/alloy microstructure and
      stainless steel like interfaces is described. In particular, 15-nm Fe/FeCr
      nanoparticles with a stainless steel like interface are prepared. These particles
      show a unique morphological transformation that is induced by surface oxidation,
      oxide passivation, and vacancy coalescence. This Kirkendall diffusion results in
      a tailorable oxide layer thickness, Fe-core size, as well as void size and
      symmetry. Much like the interface of bulk stainless steel, the interfacial FeCr
      oxide passivates oxidation, resulting in self-limited diffusion. Because of this,
      a highly uniform and stable core-void-shell morphology is observed. 

PMID- 23881844
TI  - Multiple contextual control over non-arbitrary relational responding and a
      preliminary model of pragmatic verbal analysis.
AB  - The aims of the current study were (i) to explore the flexibility and
      generalizability of non-arbitrary relational contextual control in human
      participants and (ii) to provide a simple empirical model of pragmatic verbal
      analysis, a key element in the relational frame theory approach to problem
      solving. Participants were trained to respond to abstract shapes as cues for
      responding in accordance with non-arbitrary relations of sameness, difference and
      opposition. Next, sameness, difference and opposition relational responding was
      brought under additional contextual control by arbitrary B1-B3 stimuli, such
      that, depending on the B stimulus presented, relational responding was applied to
      one of three distinct physical dimensions of multidimensional shapes. Equivalence
      training and testing was then provided such that participants showed derived
      relations between the B stimuli and three novel arbitrary C stimuli. Two
      additional cues were then trained such that they occasioned comparative
      (more/less) relations. A final test showed that the C stimuli exerted contextual
      control over physical dimensions in the novel context of more/less/same non
      arbitrary relational responding. These findings provide a simple, preliminary
      model of pragmatic verbal analysis. 

PMID- 23881843
TI  - Contribution of water molecules in the spontaneous release of protein by graphene
      sheets.
AB  - Applications of graphene sheets in the fields of biosensors and biomedical
      devices are limited by the aqueous solubility of graphene. Consequently,
      understanding the role of water molecules in the aggregation or dispersion of
      graphene in aqueous solution with a biomolecule is of vital importance to its
      application. Herein, protein is spontaneously released by the layer-to-layer
      aggregation of two single-layer graphene sheets due to van der Waals force
      between the sheets. The properties of water molecules, including density and
      dynamics, are discussed in detail. The dynamic behavior of aggregation of
      graphene sheets is triggered by the dynamics of water molecules. To stabilize
      dispersed graphene sheets in aqueous solution, the density of water molecules
      between the graphene sheets should be larger than 0.83 g cm(-3), and graphene
      modified by hydroxyl groups could be a good choice. The stability of a model
      protein on the graphene sheet is studied to investigate the biological
      compatibility of graphene sheets. To be a material with good biocompatibility,
      graphene should be functionalized by hydrophilic groups. The results presented
      herein could be helpful in the research and application of graphene sheets in the
      fields of biomaterials, biosensors, and biomedical devices.

PMID- 23881845
TI  - DL4-mediated Notch signaling is required for the development of fetal alphabeta
      and gammadelta T cells.
AB  - T-cell development depends upon interactions between thymocytes and thymic
      epithelial cells (TECs). The engagement of delta-like 4 (DL4) on TECs by Notch1
      expressed by blood-borne BM-derived precursors is essential for T-cell commitment
      in the adult thymus. In contrast to the adult, the earliest T-cell progenitors in
      the embryo originate in the fetal liver and migrate to the nonvascularized fetal
      thymus via chemokine signals. Within the fetal thymus, some T-cell precursors
      undergo programmed TCRgamma and TCRdelta rearrangement and selection, giving rise
      to unique gammadelta T cells. Despite these fundamental differences between fetal
      and adult T-cell lymphopoiesis, we show here that DL4-mediated Notch signaling is
      essential for the development of both alphabeta and gammadelta T-cell lineages in
      the embryo. Deletion of the DL4 gene in fetal TECs results in an early block in
      alphabeta T-cell development and a dramatic reduction of all gammadelta T-cell
      subsets in the fetal thymus. In contrast to the adult, no dramatic deviation of T
      cell precursors to alternative fates was observed in the fetal thymus in the
      absence of Notch signaling. Taken together, our data reveal a common requirement
      for DL4-mediated Notch signaling in fetal and adult thymopoiesis. 

PMID- 23881846
TI  - Benefit of warfarin compared with aspirin in patients with heart failure in sinus
      rhythm: a subgroup analysis of WARCEF, a randomized controlled trial.
AB  - BACKGROUND: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction
      (WARCEF) trial found no difference in the primary outcome between warfarin and
      aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus
      rhythm. However, it is unknown whether any subgroups benefit from warfarin or
      aspirin. METHODS AND RESULTS: We used a Cox model stepwise selection procedure to
      identify subgroups that may benefit from warfarin or aspirin on the WARCEF
      primary outcome. A secondary analysis added major hemorrhage to the outcome. The
      primary efficacy outcome was time to the first to occur of ischemic stroke,
      intracerebral hemorrhage, or death. Only age group was a significant treatment
      effect modifier (P for interaction, 0.003). Younger patients benefited from
      warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100
      patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001).
      In older patients, therapies did not differ (9.91 versus 9.01 events per 100
      patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44).
      With major hemorrhage added, in younger patients the event rate remained lower
      for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio,
      0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it
      became significantly higher for warfarin (11.80 versus 9.35 per 100 patient
      years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03).
      CONCLUSIONS: In patients <60 years, warfarin improved outcomes over aspirin with
      or without inclusion of major hemorrhage. In patients >=60 years, there was no
      treatment difference, but the aspirin group had significantly better outcomes
      when major hemorrhage was included.

PMID- 23881848
TI  - Phosphatidylinositol 3-phosphate, a lipid that regulates membrane dynamics,
      protein sorting and cell signalling.
AB  - Phosphatidylinositol 3-phosphate (PtdIns3P) is generated on the cytosolic leaflet
      of cellular membranes, primarily by phosphorylation of phosphatidylinositol by
      class II and class III phosphatidylinositol 3-kinases. The bulk of this lipid is
      found on the limiting and intraluminal membranes of endosomes, but it can also be
      detected in domains of phagosomes, autophagosome precursors, cytokinetic bridges,
      the plasma membrane and the nucleus. PtdIns3P controls cellular functions through
      recruitment of specific protein effectors, many of which contain FYVE or PX
      domains. Cellular processes known to be controlled by PtdIns3P and its effectors
      include endosomal fusion, sorting and motility, autophagy, cytokinesis, regulated
      exocytosis and signal transduction. Here we discuss how Ptdins3P is generated on
      specific cellular membranes, how its localizations and functions can be studied,
      and how its effectors serve to control cellular functions.

PMID- 23881847
TI  - Prognostic value of indeterminable anaerobic threshold in heart failure.
AB  - BACKGROUND: In patients with heart failure (HF), during maximal cardiopulmonary
      exercise test, anaerobic threshold (AT) is not always identified. We evaluated
      whether this finding has a prognostic meaning. METHODS AND RESULTS: We recruited
      and prospectively followed up, in 14 dedicated HF units, 3058 patients with
      systolic (left ventricular ejection fraction <40%) HF in stable clinical
      conditions, New York Heart Association class I to III, who underwent clinical,
      laboratory, echocardiographic, and cardiopulmonary exercise test investigations
      at study enrollment. We excluded 921 patients who did not perform a maximal
      exercise, based on lack of achievement of anaerobic metabolism (peak respiratory
      quotient <=1.05). Primary study end point was a composite of cardiovascular death
      and urgent cardiac transplant, and secondary end point was all-cause death.
      Median follow-up was 3.01 (1.39-4.98) years. AT was identified in 1935 out of
      2137 patients (90.54%). At multivariable logistic analysis, failure in detecting
      AT resulted significantly in reduced peak oxygen uptake and higher metabolic
      exercise and cardiac and kidney index score value, a powerful prognostic
      composite HF index (P<0.001). At multivariable analysis, the following variables
      were significantly associated with primary study end point: peak oxygen uptake (%
      pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97-0.98),
      ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01-1.03), hemoglobin (P<0.05;
      HR=0.931; CI=0.87-1.00), left ventricular ejection fraction (P<0.001; HR=0.948;
      CI=0.94-0.96), renal function (modification of diet in renal disease; P<0.001;
      HR=0.990; CI=0.98-0.99), sodium (P<0.05; HR=0.967; CI=0.94-0.99), and AT
      nonidentification (P<0.05; HR=1.41; CI=1.06-1.89). Nonidentification of AT
      remained associated to prognosis also when compared with metabolic exercise and
      cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09-1.10). Similar results
      were obtained for the secondary study end point. CONCLUSIONS: The inability to
      identify AT most often occurs in patients with severe HF, and it has an
      independent prognostic role in HF.

PMID- 23881849
TI  - Effect of 3-bromopyruvic acid on human erythrocyte antioxidant defense system.
AB  - 3-Bromopyruvate (3-BP) is a promising compound for anticancer therapy, its main
      mode of action being the inhibition of glycolytic enzymes, but this compound also
      induces oxidative stress. This study aimed at characterisation of the effect of 3
      BP on the antioxidant defense system of erythrocytes. Suspensions of erythrocytes
      in PBS containing 5 mM glucose were treated with different concentration of 3-BP
      at 37 degrees C for 1 h. Activities of antioxidant enzymes were estimated by
      standard colorimetric methods. The antioxidant capacity of erythrocytes was
      estimated using the 2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonic acid)
      (ABTS(*+)) decolorisation assay and ferricyanide reduction. The content of
      reduced and oxidized glutathione was estimated fluorimetrically with o
      phtalaldehyde. 3-BP did not affect the integrity of the erythrocyte membrane
      (lack of changes in the osmotic fragility). However, it induced oxidative stress
      in erythrocytes, as evidenced by the decrease in the content of acid-soluble
      thiols and reduced glutathione (GSH). Superoxide dismutase (SOD) and glutathione
      S-transferase (GST) activities were significantly decreased. 3-BP also decreased
      the transmembrane reduction of ferricyanide. Thus induction of oxidative stress
      in erythrocytes by 3-BP is due to depletion of glutathione and inhibition of
      antioxidant enzymes.

PMID- 23881850
TI  - Evaluation of first-pass cytochrome P4503A (CYP3A) and P-glycoprotein activities
      using felodipine and hesperetin in combination in Wistar rats and everted rat gut
      sacs in vitro.
AB  - The effects of hesperetin on the pharmacokinetics and the role of P-glycoprotein
      (P-gp) in the transport of felodipine were investigated in rats and in vitro.
      Felodipine was administered orally (10 mg/kg) without or with hesperetin (25, 50
      and 100 mg/kg) to rats for 15 consecutive days. Blood samples were collected at
      different time intervals on 1(st) day in single dose pharmacokinetic study (SDS)
      and on 15(th) day in multiple dose pharmacokinetic study (MDS). The area under
      the plasma concentration-time curve (AUC0-infinity ) and the peak plasma
      concentration (Cmax ) of felodipine were dose-dependently increased in SDS and
      MDS with hesperetin compared to control ( p < 0.001). The half-life (t1/2 ) and
      mean residence time was longer than the control group in both studies. The role
      of P-gp determined using everted rat gut sacs in vitro by incubating felodipine
      with or without hesperetin and verapamil (typical P-gp and CYP3A4 inhibitor). The
      in vitro experiments revealed that the verapamil and hesperetin increased the
      intestinal absorption of felodipine (p < 0.01). Concurrent use of hesperetin
      dramatically altered the pharmacokinetics of felodipine leading to an increase in
      systemic exposure. The likely mechanism is inhibition of CYP3A4-mediated first
      pass metabolism and P-gp in the intestine and the liver.

PMID- 23881851
TI  - Carbon nanotubes: an example of multiscale development--a mechanistic view from
      the subnanometer to the meter scale.
AB  - We summarize the catalytic synthesis of multiwall carbon nanotubes (MWCNTs). The
      current understanding of the reaction mechanism is presented, in particular the
      catalyst design for the CCVD process is analyzed. To complement that, kinetics
      and reaction engineering aspects are discussed along with the impact of the
      reaction and reactor operation on the product properties. All these issues are
      analyzed from the perspective of the industrial synthesis and implications for
      the application of carbon nanotubes. Carbon-nanotube technology is a perfect
      example of multi-scale development and covers challenges from the nanometer to
      the meter scale. Problems, methods, and solutions characteristic for different
      scales will be highlighted. The Co/Mn catalyst is used as reference as one of the
      first commercially used technologies for the scalable production of multiwall
      carbon nanotubes. 

PMID- 23881852
TI  - "Colloid-rich" follicular neoplasm/suspicious for follicular neoplasm thyroid
      fine-needle aspiration specimens: cytologic, histologic, and molecular basis for
      considering an alternate view.
AB  - BACKGROUND: Typically, thyroid follicular neoplasm/suspicious for follicular
      neoplasm (FN/SFN) cases show moderate to marked cellularity and scant or absent
      colloid. Recently, cases have been noted with microfollicular cellularity in the
      background of moderate to abundant amount of colloid. The purpose of this study
      was to compare these "colloid-rich" FN/SFN cases to the typical FN/SFN cases.
      METHODS: Thyroid cytology specimens with the features of FN/SFN were searched in
      cytopathology files from September 2008 to June 2012. Cases with absent or
      minimal colloid were designated "typical colloid-poor" FN/SFN and cases with
      moderate to abundant colloid were designated "colloid-rich" FN/SFN. From these
      cases, those with surgical pathology resection follow-up were identified.
      Cytologic, surgical pathology resection, and molecular features (BRAF, RAS,
      RET/PTC, and PAX8-PPARgamma) were investigated for the typical colloid-poor
      FN/SFN cases and were compared with those of the colloid-rich FN/SFN cases.
      RESULTS: Of 431 FN/SFN cases with surgical pathology resection follow-up, 360
      (83.5%) cases showed features of typical colloid-poor FN/SFN and 71 (16.5%) cases
      showed features of colloid-rich FN/SFN. Papillary carcinoma was the most common
      malignant outcome for the 2 groups. Although the proportion of malignant outcome
      was similar for the 2 groups, the "colloid-rich" FN/SFN cases showed a greater
      proportion of nodular hyperplasia among the cases with benign outcome. In
      addition, the "colloid-rich" FN/SFN cases demonstrated a greater proportion of
      cases with a mutation. CONCLUSIONS: Approximately one-sixth of cases of FN/SFN
      show "colloid-rich" features. Comparison to the typical colloid-poor FN/SFN
      demonstrated similar risk for malignancy but contrasting resection outcome and
      molecular characteristics.

PMID- 23881853
TI  - Towards perfectly ordered novel ZnO/Si nano-heterojunction arrays.
AB  - The fabrication of a highly ordered novel ZnO/Si nano-heterojuntion array is
      introduced. ZnO seed layer is first deposited on the Si (P<111>) surface. The
      nucleation sites are then defined by patterning the surface through focused ion
      beam (FIB) system. The ZnO nanorods are grown on the nucleation sites through
      hydrothermal process. The whole fabrication process is simple, facile and offers
      direct control of the space, length and aspect ratio of the array. It is found
      that ZnO/Si nanojunctions show an improved interface when subjected to heat
      treatment. The recrystallization of ZnO and the tensile lattice strain of Si
      developed during the heating process contribute the enhancement of their
      photoresponses to white light. The photoluminescence (PL) measurement result of
      nano-heterojunction arrays with different parameters is discussed. 

PMID- 23881854
TI  - Enhancing the deperoxidation activity of cobalt(II)acetylacetonate by the
      addition of octanoic acid.
AB  - The homolytic scission of peroxides with catalytic amounts of cobalt(II)
      complexes is used in several industrial oxidation processes. In this
      contribution, we report that addition of small amounts of octanoic acid
      significantly enhances the catalytic deperoxidation activity of the
      cobalt(II)acetylacetonate complex. We attribute this to the stabilization of the
      Co--OOR bond upon coordination of octanoic acid, preventing the unimolecular
      scission. As such, the cobalt peroxo intermediate is forced to enter an
      alternative catalytic cycle which causes its rapid conversion to the highly
      reactive cobalt hydroxy. This shift in catalytic cycle results in a higher pre
      exponential rate factor, over-compensating the higher barrier of the new rate
      determining step.

PMID- 23881855
TI  - Combination of BMP-2 and 5-AZA is advantageous in rat bone marrow-derived
      mesenchymal stem cells differentiation into cardiomyocytes.
AB  - Bone morphogenetic protein-2 (BMP-2) has a crucial role in the development of
      cardiogenesis, and is used in inducing bone marrow mesenchymal stem cells
      (BMMSCs) to differentiate into cardiomyocytes. We have examined a combination of
      BMP-2 and 5-azacytidine (5-AZA) in inducing these differentiation effects. BMMSCs
      were collected and purified from bone marrow of 4-week-old Sprague-Dawley (SD)
      rats by density-gradient centrifugation and differential attachment. The fourth
      passage subculture of BMMSCs, selected by cytometry for purity and
      identification, was divided into four groups: a control group, BMP-2 treated, 5
      AZA treated, and a combination of BMP-2 and 5-AZA treatment. Expression of
      cardiac Troponin I (cTnI) and Connexin 43 (CX-43) in BMMSCs after induction were
      detected by immunofluorescence and Western blot. Flow cytometry analysis was used
      for differentiation rates and apoptosis of induced BMMSCs, through the expression
      of cardiac Troponin T (cTnT) and Annexin V-FITC & PI kit, respectively. BMP-2 can
      ameliorate apoptosis of BMMSCs caused by 5-AZA and promote the differentiation of
      BMMSCs into cardiomyocyte-like cells. Thus a combination of BMP-2 and 5-AZA can
      significantly improve the cardiac differentiation with fewer cell damage effects,
      making it a safe and effective method of induction in vitro. 

PMID- 23881856
TI  - MRI measures of cerebral physiology.

PMID- 23881857
TI  - Model selection in measures of vascular parameters using dynamic contrast
      enhanced MRI: experimental and clinical applications.
AB  - A review of the selection of models in dynamic contrast-enhanced MRI (DCE-MRI) is
      conducted, with emphasis on the balance between the bias and variance required to
      produce stable and accurate estimates of vascular parameters. The vascular
      parameters considered as a first-order model are the forward volume transfer
      constant K(trans) , the plasma volume fraction vp and the interstitial volume
      fraction ve . To illustrate the critical issues in model selection, a data-driven
      selection of models in an animal model of cerebral glioma is followed. Systematic
      errors and extended models are considered. Studies with nested and non-nested
      pharmacokinetic models are reviewed; models considering water exchange are
      considered.

PMID- 23881859
TI  - Long-lived Plasmodium falciparum specific memory B cells in naturally exposed
      Swedish travelers.
AB  - Antibodies (Abs) are critical for immunity to malaria. However, Plasmodium
      falciparum specific Abs decline rapidly in absence of reinfection, suggesting
      impaired immunological memory. This study determines whether residents of Sweden
      that were treated for malaria following international travel maintained long
      lasting malaria-specific Abs and memory B cells (MBCs). We compared levels of
      malaria-specific Abs and MBCs between 47 travelers who had been admitted with
      malaria at the Karolinska University Hospital between 1 and 16 years previously,
      eight malaria-naive adult Swedes without histories of travel, and 14 malaria
      immune adult Kenyans. Plasmodium falciparum-lysate-specific Ab levels were above
      naive control levels in 30% of the travelers, whereas AMA-1, merozoite surface
      protein-142 , and merozoite surface protein-3-specific Ab levels were similar. In
      contrast, 78% of travelers had IgG-MBCs specific for at least one malaria antigen
      (59, 45, and 28% for apical merozoite antigen-1, merozoite surface protein-1, and
      merozoite surface protein-3, respectively) suggesting that malaria-specific MBCs
      are maintained for longer than the cognate serum Abs in the absence of re
      exposure to parasites. Five travelers maintained malaria antigen-specific MBC
      responses for up to 16 years since the diagnosis of the index episode (and had
      not traveled to malaria-endemic regions in the intervening time). Thus P.
      falciparum can induce long-lasting MBCs, maintained for up to 16 years without
      reexposure. 

PMID- 23881860
TI  - LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their
      precursors, and major metabolites in rat pineal gland microdialysate.
AB  - We report a qualitative liquid chromatography-tandem mass spectrometry (LC/MS/MS)
      method for the simultaneous analysis of the three known N,N-dimethyltryptamine
      endogenous hallucinogens, their precursors and metabolites, as well as melatonin
      and its metabolic precursors. The method was characterized using artificial
      cerebrospinal fluid (aCSF) as the matrix and was subsequently applied to the
      analysis of rat brain pineal gland-aCSF microdialysate. The method describes the
      simultaneous analysis of 23 chemically diverse compounds plus a deuterated
      internal standard by direct injection, requiring no dilution or extraction of the
      samples. The results demonstrate that this is a simple, sensitive, specific and
      direct approach to the qualitative analysis of these compounds in this matrix.
      The protocol also employs stringent MS confirmatory criteria for the detection
      and confirmation of the compounds examined, including exact mass measurements.
      The excellent limits of detection and broad scope make it a valuable research
      tool for examining the endogenous hallucinogen pathways in the central nervous
      system. We report here, for the first time, the presence of N,N
      dimethyltryptamine in pineal gland microdialysate obtained from the rat.

PMID- 23881861
TI  - Optimized expression, purification and characterization of a family 11 xylanase
      (AuXyn11A) from Aspergillus usamii E001 in Pichia pastoris.
AB  - BACKGROUND: Xylanases have attracted much attention because of their potential
      applications. Unfortunately, the commercialization of xylanases is limited by
      their low catalytic activities. The aim of this study was to improve the activity
      of a xylanase by optimization of the expression conditions and to investigate its
      characterization. RESULTS: The activity of recombinant AuXyn11A (reAuXyn11A), a
      family 11 xylanase from Aspergillus usamii E001 expressed in Pichia pastoris
      GS115, reached 912.6 U mL-1 under the optimized conditions, which was 2.14 times
      as high as that expressed using the standard protocol. After the endogenous 18-aa
      propeptide had been processed in P. pastoris, reAuXyn11A (188-aa mature peptide)
      was secreted and purified with a specific activity of 22 714 U mg-1. It displayed
      maximum activity at pH 5 and 50  degrees C and was stable in the pH range 4-8 and
      at a temperature of 45  degrees C or below. Its activity was not significantly
      affected by most metal ions and EDTA. Xylooligosaccharides ranging from xylobiose
      (X2) to xylohexaose (X6) were produced from insoluble corncob xylan by
      reAuXyn11A. CONCLUSION: Its high specific activity and good enzymatic properties
      suggest that reAuXyn11A is a potential candidate for applications in industrial
      processes.

PMID- 23881862
TI  - Influence of diabetes mellitus on inappropriate and appropriate implantable
      cardioverter-defibrillator therapy and mortality in the Multicenter Automatic
      Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) Trial.
AB  - BACKGROUND: The relationship between diabetes mellitus and risk of inappropriate
      or appropriate therapy in patients receiving an implantable cardioverter
      defibrillator (ICD) and resynchronization therapy has not been investigated
      thoroughly. The effect of innovative ICD programming on therapy delivery in these
      patients is unknown. METHODS AND RESULTS: The Multicenter Automatic Defibrillator
      Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) randomized patients
      with a primary prophylactic ICD indication to 3 different types of ICD
      programming: conventional programming with a ventricular tachycardia zone of 170
      to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone >=200
      bpm (arm B), or 60-second-delayed therapy (arm C). The end points of
      inappropriate therapy, appropriate therapy, and death were assessed among 485
      patients with and 998 without diabetes mellitus. Innovative ICD programming
      reduced the risk of inappropriate therapy regardless of diabetes mellitus,
      although a trend toward a more pronounced effect of high-rate cutoff programming
      was seen in patients without diabetes mellitus (P for interaction=0.06). Diabetes
      mellitus was associated with a decreased risk of inappropriate therapy (hazard
      ratio, 0.54; 95% confidence interval, 0.36-0.80; P=0.002) and increased risk of
      appropriate therapy (hazard ratio, 1.58; 95% confidence interval, 1.17-2.14;
      P=0.003). In diabetic patients, there was significantly increased risk of death
      in those who had inappropriate therapy (hazard ratio, 4.17; 95% confidence
      interval, 1.52-11.40; P=0.005) and appropriate therapy (hazard ratio, 2.49; 95%
      confidence interval, 1.06-5.87; P=0.037) compared with those who did not.
      CONCLUSIONS: Innovative high-rate cutoff or delayed ICD programming was
      associated with a reduction in inappropriate therapy in patients with and without
      diabetes mellitus. Diabetes mellitus was associated with lower risk of
      inappropriate therapy but higher risk of appropriate therapy. Appropriate and
      inappropriate ICD therapy was associated with increased mortality in diabetic
      patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. UNIQUE
      IDENTIFIER: NCT00947310.

PMID- 23881863
TI  - Grading epithelial atypia in endoscopic ultrasound-guided fine-needle aspiration
      of intraductal papillary mucinous neoplasms: an international interobserver
      concordance study.
AB  - BACKGROUND: Preoperative cytological analysis of cyst fluid from intraductal
      papillary mucinous neoplasms (IPMN) contributes to risk stratification for
      malignancy. To the authors' knowledge, agreement among pathologists in grading
      epithelial atypia in IPMN cyst fluids has not been studied to date. METHODS:
      Blinded to the histological grade, 4 observers independently graded 60 cell
      groups from endoscopic ultrasound-guided fine-needle aspiration samples of 24
      IPMNs of various grades as either 0 (nonlesional), 1 (low-grade dysplasia), 2
      (intermediate-grade dysplasia [IGD]), 3 (high-grade dysplasia), or 4 (invasive
      adenocarcinoma). The percentage of agreement and the kappa (k) coefficient were
      calculated for these 5 tiers and a reduced 2-tier grouping (low-grade [LG] [0-1
      and 0-2] vs high-grade [HG] [2-4 and 3-4]). Agreement between the 2 most
      experienced reviewers established a consensus diagnosis that was compared with
      the histological grade. RESULTS: Among the 4 reviewers there was poor agreement
      using a 5-tiered system and fair agreement with the 2-tiered system. LG and HG
      grouping of IGD did not appear to greatly affect agreement, with 54% agreement
      for grouping 0 to 2 and 3 to 4 (k = 0.45) and 52% agreement for grouping 0 to 1
      and 2 to 4 (k = 0.44). The 2 most experienced reviewers had 87% agreement for the
      0 to 2 and 3 to 4 grouping (k = 0.74) and 88% for the 0 to 1 and 2 to 4 grouping
      (k = 0.71). HG atypia on cytology with IGD grouped as LG yielded a sensitivity of
      82%, with a specificity of 70% for detecting a cyst with HG morphology.
      CONCLUSIONS: Grading cellular atypia in cyst fluids requires experience, which
      results in very good interobserver agreement and good correlation with histology
      using a 2-tiered LG and HG grading system and IGD classified as LG.

PMID- 23881864
TI  - Simultaneous separation of triterpenoid saponins and flavonoid glycosides from
      the roots of Glycyrrhiza uralensis Fisch by pH-zone-refining counter-current
      chromatography.
AB  - Glycosides including triterpenoid saponins and flavonoid glycosides are the main
      constituents of Glycyrrhiza uralensis Fisch (licorice) and exhibit prominent
      pharmacological activities. However, conventional methods for the separation of
      glycosides always cause irreversible adsorption and unavoidable loss of sample
      due to their high hydrophilicities. The present paper describes a convenient
      method for the simultaneous separation of triterpenoid saponins and flavonoid
      glycosides from licorice by pH-zone-refining counter-current chromatography.
      Ethyl acetate/n-butanol/water (2:3:5, v/v) with 10 mM TFA in the upper organic
      stationary phase and 10 mM ammonia in the lower aqueous mobile phase was used as
      the biphasic solvent system. Three triterpenoid saponins and two flavonoid
      glycosides including licorice-saponin A3 (63.3 mg), glycyrrhizic acid (342.2 mg),
      3-O-[beta-D-glucuronopyranosyl-(1 -> 2)-beta-D-galactopyranosyl]glycyrrhetic acid
      (56.0 mg), liquiritin apioside (232.6 mg), and liquiritin (386.5 mg) were
      successfully obtained from licorice ethanol extract (2 g) in one step. This
      method subtly takes advantage of the common acidic properties of triterpenoid
      saponins and flavonoid glycosides, and obviously is much more efficient and
      convenient than the previous methods. It is also the first time that the
      separation of acidic triterpenoid saponins by using pH-zone-refining counter
      current chromatography has been reported.

PMID- 23881865
TI  - The Mukaiyama aldol reaction: 40 years of continuous development.
AB  - A directed cross-aldol reaction of silyl enol ethers with carbonyl compounds,
      such as aldehydes and ketones, promoted by a Lewis acid, a reaction which is now
      widely known as the Mukaiyama aldol reaction. It was first reported in 1973, and
      this year marks the 40th anniversary. The directed cross-aldol reactions mediated
      by boron enolates and tin(II) enolates also emerged from the Mukaiyama
      laboratory. These directed cross-aldol reactions have become invaluable tools for
      the construction of stereochemically complex molecules from two carbonyl
      compounds. This Minireview provides a succinct historical overview of their
      discoveries and the early stages of their development. 

PMID- 23881866
TI  - Saturation recovery single-shot acquisition (SASHA) for myocardial T(1) mapping.
AB  - PURPOSE: To validate a new saturation recovery single-shot acquisition (SASHA)
      pulse sequence for T1 mapping and to compare SASHA T1 values in heart failure
      patients and healthy controls. THEORY: The SASHA sequence consists of 10
      electrocardiogram-triggered single-shot balanced steady-state free precession
      images in a breath-hold. The first image is acquired without magnetization
      preparation and the remaining nine images follow saturation pulses with variable
      saturation recovery times. METHODS: SASHA was validated through Bloch equation
      simulations, Monte Carlo simulations, and phantom experiments. Pre- and
      postcontrast myocardial and blood T1 values were measured in 29 healthy
      volunteers and 7 patients with heart failure. RESULTS: SASHA T1 values had
      excellent agreement (bias, 5 +/- 5 ms) with spin echo experiments in phantoms
      with a wide range of physiologic T1 and T2 values and its accuracy was
      independent of flip angle, absolute T1 , T2 , and heart rate. The average
      baseline myocardial T1 in heart failure patients was higher than in healthy
      controls (1200 +/- 32 vs. 1170 +/- 9 ms, P < 0.05) at 1.5T, as was the calculated
      blood-tissue partition coefficient, lambda, (0.42 +/- 0.04 vs. 0.38 +/- 0.02, P <
      0.05), consistent with diffuse myocardial fibrosis. CONCLUSIONS: The SASHA
      sequence is a simple and fast approach to in vivo T1 mapping with good accuracy
      in simulations and phantom experiments.

PMID- 23881867
TI  - Reciprocal modulation of C/EBP-alpha and C/EBP-beta by IL-13 in activated
      microglia prevents neuronal death.
AB  - In response to aggravation by activated microglia, IL-13 can significantly
      enhance ER stress induction, apoptosis, and death via reciprocal signaling
      through CCAAT/enhancer-binding protein alpha (C/EBP-alpha) and C/EBP-beta (C/EBP
      beta). This reciprocal signaling promotes neuronal survival. Since the induction
      of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor
      gamma/heme oxygenase 1 (PPAR-gamma/HO-1) by IL-13 plays a crucial role in the
      promotion of and protection from activated microglia, respectively; here, we
      investigated the role of IL-13 in regulating C/EBPs in activated microglia and
      determined its correlation with neuronal function. The results revealed that IL
      13 significantly enhanced C/EBP-alpha/COX-2 expression and PGE2 production in LPS
      treated microglial cells. Paradoxically, IL-13 abolished C/EBP-beta/PPAR-gamma/HO
      1 expression. IL-13 also enhanced ER stress-evoked calpain activation by
      promoting the association of C/EBP-beta and PPAR-gamma. SiRNA-C/EBP-alpha
      effectively reversed the combined LPS-activated caspase-12 activation and IL-13
      induced apoptosis. In contrast, siRNA-C/EBP-beta partially increased microglial
      cell apoptosis. By NeuN immunochemistry and CD11b staining, there was improvement
      in the loss of CA3 neuronal cells after intrahippocampal injection of IL-13. This
      suggests that IL-13-enhanced PLA2 activity regulates COX-2/PGE2 expression
      through C/EBP-alpha activation. In parallel, ER stress-related calpain
      downregulates the PPAR-gamma/HO-1 pathway via C/EBP-beta and leads to aggravated
      death of activated microglia via IL-13, thereby preventing cerebral inflammation
      and neuronal injury. 

PMID- 23881868
TI  - The lectin of Dolichos biflorus agglutinin recognises glycan epitopes on the
      surface of a subset of cardiac progenitor cells.
AB  - The discovery of adult cardiac progenitor cells (CPCs) provides a promising way
      for treating heart disease; however, their surface characteristics that play a
      critical role in regulating their maintenance, self-renewal, migration, and
      differentiation have not been fully investigated. One subpopulation of Dolichos
      biflorus agglutinin (DBA)-positive cells was identified in the heart of adult
      mice. Flow cytometry showed that 3.7% of heart cells could be labeled by FITC
      conjugated DBA. BrdU pulse-chase showed that 55-75% of DBA(+) cells were CPCs.
      Evidences from 5-FU-induced myelosuppression along with BrdU pulse-chasing
      suggests that DBA-positive cells are proliferative. Furthermore, DBA positive
      cells display a cologenic appearance in vivo. Our findings suggest that DBA
      positive cells in the heart of adult mouse contained a subset of CPCs, and DBA
      reactivity is one novel surface characteristic on CPCs. 

PMID- 23881870
TI  - Growing catenated nitrogen atom chains.

PMID- 23881869
TI  - In vivo three-dimensional molecular imaging with Biosensor Imaging of Redundant
      Deviation in Shifts (BIRDS) at high spatiotemporal resolution.
AB  - Spectroscopic signals which emanate from complexes between paramagnetic
      lanthanide (III) ions (e.g. Tm(3+)) and macrocyclic chelates (e.g. 1,4,7,10
      tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate, or DOTMA(4-))
      are sensitive to physiology (e.g. temperature). Because nonexchanging protons
      from these lanthanide-based macrocyclic agents have relaxation times on the order
      of a few milliseconds, rapid data acquisition is possible with chemical shift
      imaging (CSI). Thus, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS)
      which originate from nonexchanging protons of these paramagnetic agents, but
      exclude water proton detection, can allow molecular imaging. Previous two
      dimensional CSI experiments with such lanthanide-based macrocyclics allowed
      acquisition from ~12-MUL voxels in rat brain within 5 min using rectangular
      encoding of k space. Because cubical encoding of k space in three dimensions for
      whole-brain coverage increases the CSI acquisition time to several tens of
      minutes or more, a faster CSI technique is required for BIRDS to be of practical
      use. Here, we demonstrate a CSI acquisition method to improve three-dimensional
      molecular imaging capabilities with lanthanide-based macrocyclics. Using TmDOTMA(
      ), we show datasets from a 20 * 20 * 20-mm(3) field of view with voxels of ~1 MUL
      effective volume acquired within 5 min (at 11.7 T) for temperature mapping. By
      employing reduced spherical encoding with Gaussian weighting (RESEGAW) instead of
      cubical encoding of k space, a significant increase in CSI signal is obtained. In
      vitro and in vivo three-dimensional CSI data with TmDOTMA(-), and presumably
      similar lanthanide-based macrocyclics, suggest that acquisition using RESEGAW can
      be used for high spatiotemporal resolution molecular mapping with BIRDS.

PMID- 23881871
TI  - The frequency and cancer risk associated with the atypical cytologic diagnostic
      category in endoscopic ultrasound-guided fine-needle aspiration specimens of
      solid pancreatic lesions: a meta-analysis and argument for a Bethesda System for
      Reporting Cytopathology of the Pancreas.
AB  - BACKGROUND: The atypical cytologic diagnostic category is ambiguous and presents
      a management problem for pathologists and clinicians. This meta-analysis reviewed
      the frequency and cancer risk associated with atypical diagnoses in endoscopic
      ultrasound-guided fine-needle aspiration (EUS-FNA) specimens of solid pancreatic
      lesions. METHODS: PubMed and Scopus were searched using the keywords "EUS-FNA"
      and "pancreas." Articles were screened focusing on studies of solid lesions.
      Studies with information regarding the frequency and outcomes of atypical
      diagnoses were included; the "suspicious" category was excluded from the
      analysis. The frequency of atypical diagnoses and the associated risk were
      calculated using the Comprehensive Meta-Analysis software. The authors assessed
      whether the following factors explained the heterogeneity of the studies: rapid
      on-site interpretation; type of reference standard; the study type, size, and
      site; and the frequency of inadequate, atypical, and positive categories.
      RESULTS: A total of 23 studies with complete data regarding atypical diagnoses
      were identified, 12 of which had complete data available regarding outcomes. The
      frequency of the atypical category ranged from 1% to 14% (mean, 5.3%; 95%
      confidence interval, 4.1%-6.9%). The risk of malignancy associated with an
      atypical diagnosis ranged from 25% to 100% (mean, 58%; 95% confidence interval,
      47%-69%). There was significant heterogeneity noted among the studies (I-squared,
      62%; P = .0004). The frequency of the atypical category and its associated risk
      were found to be correlated only with the frequency of the specimens being
      positive for malignancy. CONCLUSIONS: The rate of atypical diagnoses of the
      pancreas is similar to that of the thyroid but the risk of malignancy is higher.
      Significant heterogeneity exists among the studies reporting atypical diagnoses.
      There is a need for standardization of the reporting and management of atypical
      diagnoses in EUS-FNA specimens from the pancreas.

PMID- 23881872
TI  - Multivariate linear regression of high-dimensional fMRI data with multiple target
      variables.
AB  - Multivariate regression is increasingly used to study the relation between fMRI
      spatial activation patterns and experimental stimuli or behavioral ratings. With
      linear models, informative brain locations are identified by mapping the model
      coefficients. This is a central aspect in neuroimaging, as it provides the sought
      after link between the activity of neuronal populations and subject's perception,
      cognition or behavior. Here, we show that mapping of informative brain locations
      using multivariate linear regression (MLR) may lead to incorrect conclusions and
      interpretations. MLR algorithms for high dimensional data are designed to deal
      with targets (stimuli or behavioral ratings, in fMRI) separately, and the
      predictive map of a model integrates information deriving from both neural
      activity patterns and experimental design. Not accounting explicitly for the
      presence of other targets whose associated activity spatially overlaps with the
      one of interest may lead to predictive maps of troublesome interpretation. We
      propose a new model that can correctly identify the spatial patterns associated
      with a target while achieving good generalization. For each target, the training
      is based on an augmented dataset, which includes all remaining targets. The
      estimation on such datasets produces both maps and interaction coefficients,
      which are then used to generalize. The proposed formulation is independent of the
      regression algorithm employed. We validate this model on simulated fMRI data and
      on a publicly available dataset. Results indicate that our method achieves high
      spatial sensitivity and good generalization and that it helps disentangle
      specific neural effects from interaction with predictive maps associated with
      other targets.

PMID- 23881873
TI  - Cost implications of treatment non-completion in a forensic personality disorder
      service.
AB  - BACKGROUND: A high proportion of individuals admitted to specialist secure
      hospital services for treatment of personality disorder do not complete
      treatment. Non-completion has been associated with poorer treatment outcomes and
      increased rates of recidivism and hospital readmission, when compared with
      individuals who do complete treatment or who do not receive treatment at all.
      AIMS: In this study, we sought to determine the economic consequences of non
      completion of treatment, using case study data from a secure hospital sample.
      Both health and criminal justice service perspectives were taken into account.
      METHODS: Data were collected from a medium secure hospital personality disorder
      unit. A probabilistic decision-analytic model was constructed, using a Markov
      cohort simulation with 10,000 iterations. The expected cost differential between
      those who do and those who do not complete treatment was estimated, as was the
      probability of a cost differential over a 10-year post-admission time horizon.
      RESULTS: On average, in the first 10 years following admission, those who do not
      complete treatment go on to incur L52,000 more in costs to the National Health
      Service and criminal justice system than those who complete treatment. The model
      estimates that the probability that non-completers incur greater costs than
      completers is 78%. CONCLUSION: It is possible that an improvement in treatment
      completion rates in secure hospital personality disorder units would lead to some
      cost savings. This might be achievable through better selection into treatment or
      improved strategies for engagement and retention. Our study highlights a
      financial cost to society of individuals discharged from secure hospital care
      when incompletely treated. We suggest that it could, therefore, be useful for
      secure hospitals to introduce routine monitoring of treatment completion.

PMID- 23881874
TI  - High water content hydrogel with super high refractive index.
AB  - Transparent, high water content (>65%), and cytocompatible hydrogels, which also
      possess super high refractive indices (RI > 1.5), are needed for ophthalmological
      applications. Most hydrogels can achieve either high RI or high water content but
      not both in the same system because water is a low RI material. Here, high water
      content/high RI hydrogels fabricated through elevated-temperature UV
      polymerization of an aqueous solution of acrylamide (AM) and methacrylamide (MAM)
      with tri(ethylene glycol) dimethacrylate (TEDA) crosslinker are reported. By
      varying the AM:MAM ratios (2:8 to 8:2) and crosslinker density (5 to 11 mol %),
      it is discovered that high water content (66%) AM:MAM copolymer hydrogels
      exhibiting anomalously high refractive indices (1.53); they are also colorless,
      transparent (99.4%), and cytocompatible with human keratinocytes. 

PMID- 23881875
TI  - Direct observation of molecular orbital mixing in a solvated organometallic
      complex.

PMID- 23881877
TI  - Human psychobiology of MDMA or 'Ecstasy': an overview of 25 years of empirical
      research.
AB  - AIMS: This paper aimed to review how scientific knowledge about the human
      psychobiology of MDMA has developed over time. METHODS: In this paper, the
      empirical findings from earlier and later studies will be reviewed. RESULTS: When
      MDMA was a 'novel psychoactive substance', it was not seen as a drug of abuse, as
      it displayed loss of efficacy. However, recreational users display a unique
      pattern of increasing doses, deteriorating cost-benefit ratios, and voluntary
      cessation. MDMA increases body temperature and thermal stress, with cortisol
      levels increased by 800% in dance clubbers. It can be extremely euphoric,
      although negative moods are also intensified. MDMA causes apoptosis (programmed
      cell death) and has been investigated for cancer therapy because of its anti
      lymphoma properties. Recreational users show deficits in retrospective memory,
      prospective memory, higher cognition, problem solving, and social intelligence.
      Basic cognitive skills remain intact. Neuroimaging studies show reduced serotonin
      transporter levels across the cerebral cortex, which are associated with
      neurocognitive impairments. Deficits also occur in sleep architecture, sleep
      apnoea, complex vision, pain, neurohormones, and psychiatric status. Ecstasy/MDMA
      use during pregnancy leads to psychomotor impairments in the children.
      CONCLUSIONS: The damaging effects of Ecstasy/MDMA are far more widespread than
      was realized a few years ago, with new neuropsychobiological deficits still
      emerging.

PMID- 23881878
TI  - Substitutional potential of mephedrone: an analysis of the subjective effects.
AB  - OBJECTIVE: In the past 25-30 years, a large number of synthetic and non-synthetic
      drugs have appeared on the recreational scene, but with the exception of 4
      methylmethcathinone (mephedrone), none of these substances reached the popularity
      of ecstasy [3,4-methylenedioxy-N-methylamphetamine, (MDMA)]. Authors aimed to
      determine the subjective effects of mephedrone in order to understand how
      mephedrone can serve as a potential substitute for entactogens, such as MDMA.
      METHODS: One hundred forty-five mephedrone users--recruited by snowball method-
      filled out a questionnaire on their patterns of use and experienced subjective
      effects of mephedrone. RESULTS: Factor analysis revealed six factors of
      mephedrone-induced subjective effects: positive emotions, sensibility, adverse
      somatic effects, adverse psychological effects, stimulant effects, and
      psychedelic effects. A preference list of subjective effects indicates that
      mephedrone is popular primarily for its psychostimulant and entactogen effects.
      Latent class analysis identified two classes of mephedrone users, with closely
      parallel profiles. The two classes differed in severity of subjective experience
      in a way that was consistent across the six dimensions. CONCLUSIONS: By having
      similar subjective effects as MDMA and other entactogens, mephedrone seems able
      to substitute other enactogenic stimulants.

PMID- 23881880
TI  - Novel psychoactive substances as a novel challenge for health professionals:
      results from an Italian survey.
AB  - INTRODUCTION: Novel psychoactive substances (NPS; a.k.a. 'legal highs' or 'smart
      drugs') are advertised online as 'safe' and 'legal' natural/synthetic analogues
      of controlled illicit drugs. However, only little research has been carried out
      in identifying the health professionals' knowledge and expertise relating to the
      intake of these compounds. METHODS: Data presented here refer to the Italian
      component of the European Union-wide, European Commission-funded, ReDNet project
      survey. An ad-hoc questionnaire was administered to professionals from the
      departments of Addiction, Psychiatry, Paediatrics and Emergency Room Services in
      Italy. RESULTS: The interviewees' sample included 243 professionals, mostly from
      the departments of Addiction (35%) and Psychiatry (28.4%). Overall, interviewees
      self-reported a poor technical knowledge relating to NPS; some 27% of respondents
      confirmed of not being aware if their patients presented with a previous history
      of NPS misuse. DISCUSSION: Novel psychoactive substances prevalence of misuse was
      not considered to be an unusual phenomenon in Italy, and most health
      professionals appeared to have concerns relating to associated medical and
      psychopathological risks, especially in terms of aggression/psychomotor
      agitation. Overall, most respondents reported the need to have better access to
      NPS-related reliable sources of information.

PMID- 23881879
TI  - Promoting innovation and excellence to face the rapid diffusion of novel
      psychoactive substances in the EU: the outcomes of the ReDNet project.
AB  - OBJECTIVES: The recent emergence of new psychoactive compounds (novel
      psychoactive substances (NPS)) has raised prominent challenges in the fields of
      drug policy, substance use research, public health and service provision. The
      Recreational Drugs European Network project, funded by the European Commission,
      was implemented to improve the information stream to young people and
      professionals about effects/risks of NPS by identifying online products and
      disseminating relevant information through technological tools. METHODS: Regular
      multilingual qualitative assessments of websites, drugs fora and other online
      resources were carried out using the Google search engine in eight languages from
      collaborating countries. These included the following: the UK, Norway, Belgium,
      Germany, Hungary, Poland, Italy and Spain. Products were tested and prevention
      messages were developed and disseminated via technological tools such as
      interactive websites, SMS alert, social networking (Facebook, Twitter),
      Multimedia (You Tube), Smartphone applications (iPhone) and virtual learning
      environments (Second Life). RESULTS: The Recreational Drugs European Network
      project established itself as the first Europe-wide prevention programme designed
      for NPS based on the efficacy of novel information and communication technology
      based forms of intervention. More than 650 NPS products and combinations were
      identified; relevant information was disseminated to target population and advice
      was given to both European Union/international agencies and national policy
      makers. CONCLUSIONS: Web-monitoring activities are essential for mapping the
      diffusion of NPS and the use of technological tools can be successfully
      incorporated in specific prevention programmes. Furthermore, the involvement of
      multi-disciplinary international partnerships was and continues to be fundamental
      for responding to such a prominent challenge.

PMID- 23881881
TI  - Consumption of new psychoactive substances in a Spanish sample of research
      chemical users.
AB  - OBJECTIVE: To know the pattern of use of new psychoactive substances (NPSs) in a
      Spanish sample of research chemical (RC) users and to deepen the RC user profile
      and risk reduction strategies employed. METHODS: This study is a cross-sectional
      survey by means of a specific questionnaire. Recruitment was carried out at music
      festivals, at non-governmental organizations (NGOs), and through announcements on
      an online forum. Two RC user profiles were defined, according to whether they
      search information through online forums. RESULTS: A total of 230 users
      participated. The most frequent RCs were hallucinogenic phenethylamines (2C-B
      80.0%, 2C-I 39.6%) and cathinones (methylone 40.1%, mephedrone 35.2%). The most
      frequent combination of RC with other illegal drugs was with cannabis (68.6%) and
      2C-B with MDMA (28.3%). Subjects who are consulting drug forums (group 1) use
      more RC, obtain RC by Internet, and use more frequently risk prevention
      strategies. Regarding the risk-reduction strategies in this group, users sought
      information concerning RC before consuming them (100%), used precision scales to
      calculate dosage (72.3%), and analyzed the contents before consumption (68.8%).
      CONCLUSIONS: There is a specific RC user profile with extensive knowledge and
      consumption of substances, using different strategies to reduce risks associated
      to its consumption.

PMID- 23881882
TI  - Presence and composition of cathinone derivatives in drug samples taken from a
      drug test service in Spain (2010-2012).
AB  - OBJECTIVE: The aim of this study was to describe the presence and composition of
      cathinone derivatives (CDs) in drug samples analyzed at a Drug Testing Service.
      MATERIAL AND METHODS: Data provided by the Drug Testing Service at Energy Control
      (a Spanish organization working in risk reduction among recreational drug users)
      were obtained from samples delivered as, or containing CDs, between January 2010
      and June 2012. Specimens were identified by combining thin layer chromatography
      and gas chromatography associated with mass spectrometry. RESULTS: Two hundred
      and thirty-seven (3.8%) of the 6199 samples were delivered as, or contained CDs.
      22 different CDs were detected, alone or in different combinations. Methylone
      (24.9%), mephedrone (24.5%), 4-methylethcathinone (9.28%), and
      methylenedioxypyrovalerone (6.8%) were the most common CDs. These substances were
      also found in 80 (1.3%) of 6042 samples delivered allegedly containing drugs
      different from CDs (such as 3,4-methylenedioxy-N-methylamphetamine (MDMA),
      amphetamines, ketamine...). CONCLUSIONS: Cathinone derivatives were markedly
      present in the Spanish drug market during the studied period. There is no
      evidence to conclude that use of CDs will become widespread or relevant for
      public health, but the phenomenon must be followed, as the potential risks of
      these new drugs of abuse are substantial.

PMID- 23881883
TI  - MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H
      cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') toxicity: a brief
      overview and update.
AB  - OBJECTIVES: MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H
      cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') is a psychoactive
      substance, sold primarily over the Internet and in 'head' shops as a 'legal
      high'. Synthesised and used as a research chemical in the 1990s, MDAI has
      structural similarities to MDMA (3,4-methylenedioxy-N-methylamphetamine) and
      shares its behavioural properties. Recreational use of MDAI appears to have
      started in Europe around 2007, with a noticeable increase after 2009 in the UK
      and other countries. Calls to National Poisons Information Services started in
      2010, although there were few presentations to emergency departments by patients
      complaining of undesirable physical and psychiatric effects after taking MDAI.
      Recreational use of this drug has been reported only occasionally by online user
      fora. There is little scientifically based literature on the pharmacological,
      physiological, psychopharmacological, toxicological and epidemiological
      characteristics of this drug. METHODS: Recent literature (including 'grey') was
      searched to update what is known about MDAI, especially on its toxicity. RESULTS:
      The resultant information is presented, including on the first three UK deaths
      involving MDAI use in 2011 and 2012. 'Serotonin syndrome' appears to be a
      possible factor in these fatalities. CONCLUSION: It is vital that any other
      cases, including non-fatal overdoses, are documented so that a scientific
      evidence base can be established for them.

PMID- 23881884
TI  - Recreational use of 1-(2-naphthyl)-2-(1-pyrrolidinyl)-1-pentanone hydrochloride
      (NRG-1), 6-(2-aminopropyl) benzofuran (benzofury/ 6-APB) and NRG-2 with review of
      available evidence-based literature.
AB  - OBJECTIVE: This study aimed to review the available evidence-based literature on
      novel psychoactive substances and to inform health care professionals. METHODS:
      Internet searches were carried out using Google and Yahoo by using specific key
      words. For each set of key words, the first 100 websites identified by Google and
      Yahoo were fully assessed, together with a further 5% of random samples selected
      by research randomizer of the remaining websites. Thus, a list of unique web
      forums was identified, and qualitative information was extracted. Available
      evidence-based literature were reviewed along with a user's experimentation with
      mephedrone, NRG-1, NRG-2 and Benzofury. RESULTS: It showed that when a substance
      (mephedrone) became controlled, the vendors aggressively promote the sale of
      other new compounds (NRG-1, NRG-2, Benzofury) to attract vulnerable adults. The
      characteristics, toxicity and suggested management of these new compounds (NRG-1,
      NRG-2, Benzofury) are discussed. CONCLUSIONS: The arrival of hundreds of novel
      psychoactive substances for sale online has raised a number of public health and
      legal issues. Although evidence-based literature remains limited, few studies
      identified that most products do not contain the ingredients as advertised.
      Better levels of international cooperation and rapid share of available
      information may be needed to tackle this emerging problem.

PMID- 23881885
TI  - Computer-aided (in silico) approaches in the mode-of-action analysis and safety
      assessment of ostarine and 4-methylamphetamine.
AB  - OBJECTIVE: This study exemplifies computer-aided (in silico) approaches in
      assessing the risks of new psychoactive substances emerging in the European
      Union. In this work, we (i) consider the potential of Ostarine exhibiting
      psychoactivity and (ii) anticipate potential activities and toxicities of 4
      methylamphetamine. METHOD: The approach, termed in silico target prediction,
      suggests potential protein targets modulated by compounds given their chemical
      structure. This is achieved by first establishing the associations between
      chemical structure and protein targets using data from the bioactivity database,
      ChEMBL, via the use of two different computational algorithms. On the basis of
      the associations, protein targets and consequently the mode of action of novel
      compounds were predicted. RESULTS: For Ostarine, none of the targets anticipated
      are currently known to elicit psychoactivity. Furthermore, Ostarine is unlikely
      to cross the blood-brain barrier to reach relevant target sites on the basis of
      its physicochemical properties. For 4-methylamphetamine, toxicities were
      anticipated, that is, serotonin syndrome (based on the prediction of SERT) and
      other effects similar to related substances, that is, methamphetamine.
      CONCLUSION: From the two case studies, we showed that in silico target prediction
      appears to have potential in assessing new psychoactive compounds where
      experimental data are scarce. The applicability domain of target predictions when
      applied to psychoactive compounds needs to be established in future work.

PMID- 23881886
TI  - "Spiceophrenia": a systematic overview of "spice"-related psychopathological
      issues and a case report.
AB  - OBJECTIVES: The use of synthetic cannabimimetics (SC; "spice" drugs) is
      increasing, especially among teenagers and young adults. In parallel with this,
      the number of studies describing intoxication episodes associated with psychotic
      symptoms in SC users is growing. We present both a systematic review of the
      related literature and a case report, which seems to highlight the existence of a
      possible association between SC use and psychosis. METHODS: Some 223 relevant
      studies were here identified and reviewed. Out of these, 120 full text articles
      were assessed for eligibility, and 41 were finally included in the systematic
      review. RESULTS: According to the available data from the studies here
      identified, SC's average age of users was 22.97 years, and the male/female ratio
      was 3.16:1. SC compounds most often reported in studies using biological specimen
      analysis were JWH-018, JWH-073, JWH-122, CP-47,497, and JWH-250. Mounting
      evidence seemed to suggest that psychotic symptoms such as hallucinations and
      delusions may occur in acute/chronic SC users. CONCLUSIONS: Although a clear
      causal link may not be here identified, the available evidence suggests that SC
      can trigger the onset of acute psychosis in vulnerable individuals and/or the
      exacerbation of psychotic episodes in those with a previous psychiatric history.

PMID- 23881887
TI  - The 12-month prevalence and nature of adverse experiences resulting in emergency
      medical presentations associated with the use of synthetic cannabinoid products.
AB  - OBJECTIVE: A wide range of synthetic cannabinoid products have recently become
      available through the Internet and shop fronts across the globe. Concerns about
      the consequences of their use have been prompted by increasing reports of
      emergency department presentations. METHODS: An anonymous global online survey
      was conducted using a research tool based on previous work carried out by the
      group. Data collection took place during a 4-week period at the end of 2011.
      RESULTS: Among 950 last-year users, 23 (2.4%) reported having sought emergency
      medical treatment following the use of a synthetic cannabinoid product. The most
      common presentations were panic and anxiety, followed by paranoia and breathing
      difficulties. Recent users who reported seeking emergency medical treatment were
      significantly younger (median age 20 years, interquartile range 18-22) than those
      who did not report seeking treatment (median age 23 years, interquartile range 19
      28; Mann-Whitney test, z = 2.89, p = 0.004). CONCLUSIONS: Synthetic cannabinoid
      use appears to be associated with a high prevalence of adverse experiences among
      users, especially younger users. Further research is required to determine
      whether particular compounds carry a higher risk of harm than others and to
      assess potential consequences of longer term use.

PMID- 23881888
TI  - Classical and novel psychoactive substances: rethinking drug misuse from an
      evolutionary psychiatric perspective.
AB  - In this article, ontogenetic and phylogenetic causes of drug abuse and links to
      human emotional development are considered. Some evolutionary perspectives (e.g.
      that under certain conditions, consumption of otherwise toxic alkaloids may
      confer both physical and cultural advantages) are reviewed. As described in the
      'mismatch theory', the capacity of the human genome to evolve defences against
      toxins has been outstripped by the pace of cultural change and technological
      development, such as purposeful fermentation of alcohol and more recently
      distillation of alcohol; purification and chemical manipulation of plant
      alkaloids; and the engineering of entirely novel psychoactive substances (NPS).
      The functions of the neurobiological substrates that mediate substance misuse and
      dependence are reviewed. Reasons are given why NPSs present greater cause for
      concern than plant-derived substances of abuse. We argue that evolutionary
      biology provides an important orientation for the research agenda in substance
      misuse.

PMID- 23881890
TI  - Drug concentrations in post-mortem femoral blood compared with therapeutic
      concentrations in plasma.
AB  - Therapeutic drug concentrations measured in plasma are of limited value as
      reference intervals for interpretation in post-mortem (PM) toxicology. In this
      study, drug concentration distributions were studied in PM femoral venous blood
      from 57 903 Finnish autopsy cases representing all causes of death during an 11
      year period. Cause-of-death information was obtained from death certificates
      issued by forensic pathologists. Median, mean, and upper percentile (90th, 95th,
      97.5th) concentrations were calculated for 129 drugs. To illustrate how PM median
      concentrations relate to established therapeutic ranges in plasma, a PM
      blood/plasma relationship was calculated for each drug. Males represented 75% of
      the subjects and showed a lower median age (55 yrs) than females (59 yrs). In 43%
      of these cases, blood alcohol concentration was higher than 0.20/00, and the
      median was 1.80/00. Sixty-one (47%) of the 129 drugs showed a PM blood/plasma
      relationship of 1. For 22 drugs (17%), the relationship was <1, and for 46 drugs
      (35%), the relationship was >1. No marked correlation was found between the PM
      blood/plasma relationship and the volume of distribution (Vd ). For 36 drugs,
      more than 10% of cases were fatal poisonings attributed to this drug as the main
      finding. These drug concentration distributions based on a large database provide
      a helpful reference not only to forensic toxicologists and pathologists but also
      to clinical pharmacologists in charge of interpreting drug concentrations in PM
      cases.

PMID- 23881891
TI  - PEDro systematic review update: the effectiveness of physiotherapy exercises in
      subacromical impingement syndrome.

PMID- 23881892
TI  - Increased risk of injury following red and yellow cards, injuries and goals in
      FIFA World Cups.
AB  - OBJECTIVE: To study the relationship between potentially game-disrupting
      incidents (PGDIs; red and yellow cards, goals and injuries) and the injury
      incidence in football. DESIGN: Prospective injury surveillance during three FIFA
      World Cups in 2002, 2006 and 2010. Official match statistics were obtained for
      all the matches played in the three tournaments. SETTING: 2002, 2006 and 2010
      FIFA World Cups. PARTICIPANTS: Team physicians at the 2002, 2006 and 2010 FIFA
      World Cups. MAIN OUTCOME MEASURES: Injury incidences and incidence rate ratios
      (IRRs). RESULTS: The injury incidence was significantly higher during match
      periods within the minute of, or during a five-minute period following a yellow
      card, red card, another injury or a goal (PGDIs) than during other match periods
      (76.7/1000 match hours; 95% CI (66.6 to 87.9) vs 54.0/1000 match hours (46.9 to
      61.9), p<0.001). There were significant differences in injury incidence between
      different match periods, with the highest injury incidence seen in the last 15
      min of the first half (p<0.001). The PGDIs (other than injury) had a tendency to
      increase towards the end of the game and the most frequent PGDI was a yellow
      card. There was a risk ratio of 1.17 (95% CI 1.08 to 1.26) for injury, per PGDI
      (other injuries excluded) (p<0.001), and 1.15 (95% CI 1.06 to 1.24) after
      adjusted match time (p<0.001). CONCLUSIONS: The injury incidence is high within
      the five minutes following a PGDI. For both team management and players, being
      aware of the increased risk of injury directly after a PGDI may be of clinical
      relevance, as it may enable them to take precautions in order to prevent
      injuries. There are significant differences in injury incidence between different
      match periods and game-related factors, such as PGDIs, appear partly to
      contribute to this variation.

PMID- 23881893
TI  - Practical responses to confidentiality dilemmas in elite sport medicine.
AB  - AIM: To examine the ethical challenges of upholding patient confidentiality in
      sports medicine and the practical responses of clinicians to these challenges.
      METHOD: Questionnaire survey and follow-up semi-structured interviews with the
      members of the British Olympic Association's Medical Committee and Physiotherapy
      Forum. RESULTS: Clinicians identified three contextual factors that influenced
      issues related to patient confidentiality in sports medicine: the use of
      confidentiality waivers; the facilities available for treatment; and the cultural
      norms of elite sport. They further identified interpersonal strategies used to
      lessen or eradicate conflicts, including emphasising the benefits and avoidance
      of disbenefits for athletes and the potential negative consequences for others.
      CONCLUSIONS: Aspects of clinicians' practice environment should be designed to
      enable compliance with the highest levels of ethical conduct. Professional
      associations should establish guidelines for clinicians' interpersonal conduct in
      dealing with confidentiality issues and consider their provision of ethics-based
      continuous professional development. They should also petition for the
      establishment of athletes' codes of conduct which identify a context-relevant
      understanding of 'serious harm' and how that might impact on information
      disclosure.

PMID- 23881895
TI  - Getting Scotland on the move? Reflections on a 5-year review of Scotland's
      national physical activity strategy.
AB  - The public health risks of physical inactivity have led many national governments
      to develop policies that aim to increase population levels of physical activity.
      There is however, little evidence available about the effectiveness of such
      strategies and physical activity leaders may also face challenges in securing
      sufficient levels of political will and lasting investment for physical activity.
      This article reports on a review of a national physical activity strategy in
      Scotland after 5 years of implementation and offers lessons that may assist
      policymakers, practitioners and communities seeking to mobilise political
      commitment and leadership for physical activity in their own countries. 

PMID- 23881894
TI  - Consensus criteria for defining 'successful outcome' after ACL injury and
      reconstruction: a Delaware-Oslo ACL cohort investigation.
AB  - BACKGROUND: No gold standard exists for identifying successful outcomes 1 and 2
      years after operative and non-operative management of anterior cruciate ligament
      (ACL) injury. This limits the ability of a researcher and clinicians to compare
      and contrast the results of interventions. PURPOSE: To establish a consensus
      based on expert consensus of measures that define successful outcomes 1 and 2
      years after ACL injury or reconstruction. METHODS: Members of international
      sports medicine associations, including the American Orthopaedic Society for
      Sports Medicine, the European Society for Sports Traumatology, Surgery, and Knee
      Arthroscopy and the American Physical Therapy Association, were sent a survey via
      email. Blinded responses were analysed for trends with frequency counts. A summed
      importance percentage (SIP) was calculated and 80% SIP operationally indicated
      consensus. RESULTS: 1779 responses were obtained. Consensus was achieved for six
      measures in operative and non-operative management: the absence of giving way,
      patient return to sports, quadriceps and hamstrings' strength greater than 90% of
      the uninvolved limb, the patient having not more than a mild knee joint effusion
      and using patient-reported outcomes (PRO). No single PRO achieved consensus, but
      threshold scores between 85 and 90 were established for PROs concerning patient
      performance. CONCLUSIONS: The consensus identified six measures important for
      successful outcome after ACL injury or reconstruction. These represent all levels
      of the International Classification of Functioning: effusion, giving way, muscle
      strength (body structure and function), PRO (activity and participation) and
      return to sport (participation), and should be included to allow for comparison
      between interventions.

PMID- 23881896
TI  - Imaging at London 2012 summer Olympic Games: analysis of demand and distribution
      of workload.
AB  - BACKGROUND: Very little data on the provision of imaging services at the summer
      Olympic Games have been published before. With 7.9 million Euros (L6.6 million,
      US$11 million) invested into setting up the imaging equipment at the purpose
      built polyclinics for London 2012 summer Olympics, an ideal opportunity was
      presented to study the demand and distribution of workload on imaging services at
      the games. SETTING: Imaging services within polyclinics, London 2012 summer
      Olympic Games. AIMS: To analyse the demand and distribution of workload on
      radiology services at the London 2012 summer Olympic Games. METHODS: Data on
      radiological investigations performed at London 2012 summer Olympic Games were
      retrieved from Radiology Information System-picture archiving communication
      system, ATOS medical encounter database and analysed. RESULTS: 1711 diagnostic
      and interventional procedures were performed at the Stratford Polyclinic within
      the main games village. Of these 48.8% were MRI scans, 20.2% were diagnostic
      ultrasound examinations, 23.6% were plain radiographs, 2.9% were CT scans and
      interventional procedures accounted for 4.3%. Nearly 75% of imaging was performed
      on athletes while less than 5% of the services were utilised by the workforce.
      Demand on radiology services peaked during week 2 of the games. CONCLUSIONS:
      Imaging played a substantial role in providing medical services at the London
      2012 summer Olympics.

PMID- 23881897
TI  - The IOC Diploma programme in sports medicine.

PMID- 23881898
TI  - The genetic and neuroanatomical basis of social dysfunction: lessons from
      neurofibromatosis type 1.
AB  - Neurofibromatosis type 1 (NF1) is a common genetic condition associated with
      cognitive and social dysfunction as well as abnormal brain structure. The
      pathophysiology underlying social dysfunction in NF1 is poorly understood. Here,
      we investigate for the first time whether there is a broad deficit of social
      cognition in NF1 and explore the neural correlates for these deficits. Twenty
      nine adults with NF1 and 30 controls were administered an ecologically based test
      of social cognition, The Awareness of Social Inference Test (TASIT), to identify
      deficits in emotion recognition and sarcasm detection. We employed voxel-based
      morphometry in a subset of NF1 patients (n = 16) and 16 additional controls to
      examine the neural correlates of these deficits. Results indicated that adults
      with NF1 were impaired in their ability to understand paradoxical sarcasm and
      their capacity to recognize emotion, particularly anger. TASIT performance was
      not associated with measures of attention, visuospatial skills or executive
      function. Relative to controls, gray matter (GM) volume within the right superior
      temporal gyrus (STG) was decreased, after controlling for total brain volume.
      Decreased volume in this region was significantly associated with social
      cognitive deficits in adults with NF1. We conclude that patients with NF1 are at
      high risk for a social cognitive deficit and provide evidence for a
      neuroanatomical basis for this deficit; GM volumetric reductions in the right
      STG. These findings improve our understanding of the nature of social interaction
      impairments in NF1 and add to the growing body of literature indicating the STG
      as a critical brain region for social cognition.

PMID- 23881899
TI  - Evaluation of anger management groups in a high-security hospital.
AB  - BACKGROUND: Anger management programmes for offenders typically aim to improve
      the management of emotion associated with aggressive and antisocial behaviour.
      Such programmes have been quite extensively evaluated in prison and probation
      settings, but there is less published research in forensic mental health
      settings. AIM: This study aimed to evaluate anger management groups in a high
      security hospital. METHOD: Eighty-six patients were referred for a 20-session
      anger management intervention. Outcomes were self-reported experiences of anger
      and changes in institutionally documented incidents of aggression. Incident rates
      were retrospectively reviewed for all group graduates, where data were available,
      including a comparison group of graduates who acted as their own controls.
      RESULTS: Group graduates reported sustained reductions in feelings of anger and
      positive changes in their use of aggression in reaction to provocation. Some
      reduction in incidents of physical aggression was noted when group completers
      were compared with non-completers. Incidents of verbal aggression were observed
      to increase for graduates. There was also a trend towards improvement when
      treated men were compared with men on the waiting list. CONCLUSIONS: Our findings
      contribute to the growing evidence for anger management groups for aggressive
      men, although the low-base rate of incidents, typical of such a containing and
      therapeutic hospital setting, rendered the analysis of behavioural outcomes
      difficult. IMPLICATIONS FOR PRACTICE AND RESEARCH: Anger management sessions for
      male forensic psychiatric patients can be effective in reducing incidents of
      physical aggression in response to provocation. Evaluation of treatments for
      anger is particularly difficult in secure and protective settings, where the aim
      is to keep incidents of actual physical aggression to a minimum. Further research
      of this kind is needed to test the value of self-reported reduction in angry
      feelings as an indicator of clinically useful progress.

PMID- 23881906
TI  - Positron emission tomography imaging of drug-induced tumor apoptosis with a
      caspase-triggered nanoaggregation probe.
AB  - Drug Design: An (18)F-labeled caspase-3-sensitive nanoaggregation positron
      emission tomography tracer was prepared and evaluated for imaging the caspase-3
      activity in doxorubicin-treated tumor xenografts. Enhanced retention of the (18)F
      activity in apoptotic tumors is achieved through intramolecular macrocyclization
      and in situ aggregation upon caspase-3 activation (see picture).

PMID- 23881907
TI  - Psychiatric correlates of past incarceration in the national co-morbidity study
      replication.
AB  - BACKGROUND: Mental illness and substance abuse have been increasingly linked to
      criminal justice system involvement, but this relationship has mostly been by
      survey of prison populations and inferences of excess rates of disorder made by
      noting how these rates compare with national population-based surveys of mental
      disorders. AIMS: The aim of this study is to examine associations between history
      of mental disorders, including substance misuse, with incarceration history
      within a single population-based data set. METHODS: Data were from the National
      Comorbidity Survey Replication, a nationally representative household survey of
      respondents 18 years and older conducted between 5 February 2001 and 7 April
      2003. RESULTS: Multivariate regression analysis showed the strongest independent
      risk factors for a history of incarceration were being male [odds ratio (OR) =
      6.3; p < 0.001], past receipt of welfare payments (OR = 2.1; p < 0.001), longer
      than 1 week of past homelessness (OR = 2.1; p < 0.001), not being from the
      northeast of the USA (OR = 0.31; p < 0.001) and a lifetime substance abuse or
      dependence diagnosis (OR = 4.9; p < 0.001). With the exception of welfare
      payments, these measures were also independently associated with longer (27 +
      days) incarceration. CONCLUSIONS: The socioeconomic associates of incarceration
      history were unexpected, and in line with other, differently conducted studies.
      The fact that only substance misuse disorders of all those assessed were
      independently associated with incarceration history was a surprise, given the
      multiplicity of prison surveys, which have shown higher rates of other serious
      mental disorders. Although we were unable to include measures of schizophrenia or
      similar psychosis and used impulse control disorders as surrogates for
      personality disorder, absence of a relationship between depression and
      incarceration when measured in the same way and over the same time among those
      previously incarcerated and those not, raises questions about the weight that
      should be put on the existing epidemiological perspective of mental disorder
      among prisoners.

PMID- 23881908
TI  - Vitamin D Insufficiency/Deficiency in HIV-Infected Inner City Youth.
AB  - BACKGROUND: High prevalence of vitamin D deficiency among HIV-infected
      individuals has been reported in many studies. Increasing evidence for vitamin
      D's role in innate and cell-mediated immunity suggests that vitamin D
      insufficiency or deficiency is worrisome particularly for HIV-infected
      individuals who are already at increased risk of infection. It is unknown whether
      vitamin D deficiency and supplementation will have any effects on HIV infection,
      including CD4 counts/CD4% and HIV plasma RNA. METHOD: Serum vitamin D levels, 25
      hydroxyvitamin D (25-(OH)D), were obtained from 160 HIV-infected youth, aged 2 to
      26 years as part of routine care. The HIV plasma RNA and CD4 counts were compared
      between patients with normal vitamin D and vitamin D insufficiency/deficiency.
      Individuals whose vitamin D level was <=35 ng/mL received vitamin D3
      supplementation. We compared the HIV plasma RNA, absolute CD4 counts, and CD4% in
      pre- and post-vitamin D supplementation. Categorical comparisons between the
      groups were examined using a nonparametric Fisher exact test, while continuous
      variables, pre- and post-vitamin D supplementation, were examined using a
      parametric paired samples t test. RESULTS: The majority (152 of 160; 95%) of our
      patients were African American. Only 8 (5%) of 160 had normal vitamin D. Of the
      160 patients with HIV, 37 (23.1%) had vitamin D insufficiency (25-(OH)D level
      between 21 and 35 ng/mL) and 11 of 160 (71.9%) had vitamin D deficiency (25-(OH)D
      level <=20 ng/mL). Absolute CD4 counts averaged lower in patients who have severe
      vitamin D deficiency (25-(OH)D <=10 ng/mL; mean 574.41 +/- 306.17 cells/mm(3))
      compared to those who had higher vitamin D level (mean 701.15 +/- 444.19
      cells/mm(3)). The CD4% were also lower (mean 25.12% +/- 12.5%) in those who have
      severe vitamin D deficiency compared to those whose vitamin D level was >=11
      ng/mL (mean 29.47% +/- 11.62%). The HIV plasma RNA was similar in all the groups.
      Our patients who were prescribed tenofovir (TDF) and/or efavirenz (EFV) did not
      have different vitamin D levels than patients who were prescribed other
      antiretroviral (ARV) medications. Only 60 (39.5%) of the 152 patients who
      received vitamin D supplement showed improvement in vitamin D level. Of the 60
      patients, 10 (16.7%) had normalized vitamin D level (25-(OH)D level > 35 ng/mL).
      We did not see any significant change in the absolute CD4 counts or CD4%.
      CONCLUSIONS: A higher prevalence of vitamin D insufficiency/deficiency was found
      in our study compared to the previous large cohorts. However, patients who were
      prescribed TDF/EFV did not have lower vitamin D levels. Inadequate sunlight
      exposure in temperate latitudes and the cloud effect of the Great Lakes as well
      as large number of African American participants who live in the inner city area
      with poverty and poor diet may combine to explain these results. The effect of
      ARV medications on vitamin D may be washed out by the numerous other factors
      affecting vitamin D in our patients. Severe vitamin D deficiency seemed to be
      related to lower CD4 counts and CD4% but not related to HIV plasma RNA. Vitamin D
      supplementation did not increase CD4 counts/CD4% in our study.

PMID- 23881909
TI  - Group problem-solving therapy for postnatal depression among HIV-positive and HIV
      negative mothers in Zimbabwe.
AB  - Postnatal depression (PND) is a major problem in low- and middle-income countries
      (LMICs). A total of 210 postpartum mothers attending primary care urban clinics
      were screened for PND at 6 weeks postpartum using the Edinburgh Postnatal
      Depression Scale (EPDS) and Diagnostic and Statistical Manual of Mental Disorders
      (Fourth Edition; DSM-IV) criteria for major depression. The HIV prevalence was
      14.8%. Of the 210 enrolled postpartum mothers, 64 (33%) met DSM IV criteria for
      depression. Using trained peer coun- selors, mothers with PND (n = 58) were
      randomly assigned to either group problem-solving therapy (PST, n = 30) or
      amitriptyline (n = 28). Of the 58 mothers with PND, 49 (85%) completed 6 weeks of
      group PST (n = 27) or pharmacotherapy (n = 22). At baseline, the mean EPDS score
      for participants randomized to group PST was 17.3 (standard deviation [SD] 3.7),
      while the group randomized to amitriptyline had a mean EPDS score of 17.9 (SD
      3.9; P = .581). At 6 weeks postintervention, the drop in mean EPDS score was
      greater in the PST group (8.22, SD 3.6) compared to the amitriptyline group
      (10.7, SD 2.7; P = .0097). Group PST using peer counselors is feasible,
      acceptable, and more effective compared to pharmacotherapy in the treatment of
      PND. Group PST could be integrated into maternal and child health clinics and
      preventing mother-to-child transmission of HIV programs in LMICs.

PMID- 23881910
TI  - Interactions between alcohol and the HIV entry inhibitor Maraviroc.
AB  - BACKGROUND: Alcohol use is common among people with HIV, and beliefs about
      alcohol interactions with medications predict decreased medication adherence,
      risking drug-resistant mutations. Maraviroc is an HIV entry inhibitor approved
      for treatment of both drug-sensitive and drug-resistant HIV strains. The present
      study evaluated the effects of alcohol on maraviroc pharmacokinetics and the
      effects of maraviroc on alcohol pharmacokinetics. METHODS: Ten healthy adults
      completed alcohol (1 g/kg) and placebo alcohol pharmacokinetics sessions before
      and after 7 days of maraviroc administration. RESULTS: Alcohol concentrations
      increased 12% following maraviroc. Maraviroc pharmacokinetics were unaffected by
      alcohol. CONCLUSIONS: Maraviroc treatment should not be interrupted if alcohol is
      consumed.

PMID- 23881911
TI  - Identification of Niemann-Pick C1 disease biomarkers through sphingolipid
      profiling.
AB  - Niemann-Pick type C (NPC)1 is a rare neurodegenerative disease for which
      treatment options are limited. A major barrier to development of effective
      treatments has been the lack of validated biomarkers to monitor disease
      progression or serve as outcome measures in clinical trials. Using targeted
      metabolomics to exploit the complex lipid storage phenotype that is the hallmark
      of NPC1 disease, we broadly surveyed Npc1(-/-) mouse tissues and identified
      elevated species across multiple sphingolipid classes that increased with disease
      progression. There was a striking accumulation of sphingoid bases,
      monohexosylceramides (MCs), and GM2 gangliosides in liver, and sphingoid bases
      and GM2 and GM3 gangliosides in brain. These lipids were modestly decreased
      following miglustat treatment, but markedly decreased in response to treatment
      with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD), two drugs that have shown
      efficacy in NPC1 animal models. Extending these studies to human subjects led to
      identification of sphingolipid classes that were significantly altered in the
      plasma of NPC1 patients. Plasma MCs and ceramides were elevated, whereas
      sphingoid bases were reduced in NPC1 subjects. Intervention with miglustat in
      NPC1 patients was accompanied by striking alterations in plasma (reductions in
      GM1 and GM3 gangliosides) and cerebrospinal fluid (CSF) (increased MCs)
      sphingolipids. Similar alterations were observed in the CSF from the NPC1 feline
      model following HP-beta-CD treatment. Our findings suggest that these lipid
      biomarkers may prove useful as outcome measures for monitoring efficacy of
      therapy in clinical trials. 

PMID- 23881912
TI  - New horizons for lipoprotein receptors: communication by beta-propellers.
AB  - The lipoprotein receptor (LR) family constitutes a large group of structurally
      closely related receptors with broad ligand-binding specificity. Traditionally,
      ligand binding to LRs has been anticipated to involve merely the complement type
      repeat (CR)-domains omnipresent in the family. Recently, this dogma has
      transformed with the observation that beta-propellers of some LRs actively engage
      in complex formation too. Based on an in-depth decomposition of current
      structures and sequences, we suggest that exploitation of the beta-propellers as
      binding targets depends on receptor subgroups. In particular, we highlight the
      shutter mechanism of beta-propellers as a general recognition motif for NxI
      containing ligands, and we present indications that the generalized beta
      propeller-induced ligand release mechanism is not applicable for the larger LRs.
      For the giant LR members, we present evidence that their beta-propellers may also
      actively engage in ligand binding. We therefore advocate for an increased focus
      on solving the structure-function relationship of this group of important
      biological receptors. 

PMID- 23881913
TI  - Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6.
AB  - Cholesterol homeostasis is crucial for cellular function and organismal health.
      The key regulator for the cholesterol biosynthesis is sterol-regulatory element
      binding protein (SREBP)-2. The biochemical process and physiological function of
      SREBP-2 have been well characterized; however, it is not clear how this gene is
      epigenetically regulated. Here we have identified sirtuin (Sirt)6 as a critical
      factor for Srebp2 gene regulation. Hepatic deficiency of Sirt6 in mice leads to
      elevated cholesterol levels. On the mechanistic level, Sirt6 is recruited by
      forkhead box O (FoxO)3 to the Srebp2 gene promoter where Sirt6 deacetylates
      histone H3 at lysines 9 and 56, thereby promoting a repressive chromatin state.
      Remarkably, Sirt6 or FoxO3 overexpression improves hypercholesterolemia in diet
      induced or genetically obese mice. In summary, our data suggest an important role
      of hepatic Sirt6 and FoxO3 in the regulation of cholesterol homeostasis. 

PMID- 23881915
TI  - Altered natural killer cell subset homeostasis and defective chemotactic
      responses in paroxysmal nocturnal hemoglobinuria.
AB  - In paroxysmal nocturnal hemoglobinuria (PNH), hematopoietic cells lacking
      glycosylphosphatidylinositol (GPI)-linked proteins on their surface (GPI(neg))
      exist alongside normal (GPI+) cells. Analysis of natural killer (NK) cell subsets
      in 47 PNH patients revealed that the ratio of CD56(bright):CD56(dim) NK cells
      differed in the GPI+ and GPI(neg) populations, with GPI(neg)CD56(bright) NK cells
      significantly more abundant in peripheral blood than their normal GPI+
      counterparts. Indeed, GPI+CD56(bright) NK cells were not detected in the
      peripheral blood of some patients, suggesting their trafficking to a niche
      unavailable to the GPI(neg)CD56(bright) NK cell population. Defective cellular
      trafficking in this disease was supported by findings showing differential
      chemokine receptor expression between GPI+ and GPI(neg) NK cells and impaired
      stromal cell-derived factor 1 (SDF-1)-induced chemotaxis of GPI(neg) NK cells.
      Our results indicate a role for GPI-linked proteins in NK cell subset homeostasis
      and suggest that differential chemokine responses might contribute to the balance
      of GPI+ and GPI(neg) populations in this disease. 

PMID- 23881914
TI  - DEPTOR regulates vascular endothelial cell activation and proinflammatory and
      angiogenic responses.
AB  - The maintenance of normal tissue homeostasis and the prevention of chronic
      inflammatory disease are dependent on the active process of inflammation
      resolution. In endothelial cells (ECs), proinflammation results from the
      activation of intracellular signaling responses and/or the inhibition of
      endogenous regulatory/pro-resolution signaling networks that, to date, are poorly
      defined. In this study, we find that DEP domain containing mTOR interacting
      protein (DEPTOR) is expressed in different microvascular ECs in vitro and in
      vivo, and using a small interfering RNA (siRNA) knockdown approach, we find that
      it regulates mammalian target of rapamycin complex 1 (mTORC1), extracellular
      signal-regulated kinase 1/2, and signal transducer and activator of transcription
      1 activation in part through independent mechanisms. Moreover, using limited gene
      arrays, we observed that DEPTOR regulates EC activation including mRNA expression
      of the T-cell chemoattractant chemokines CXCL9, CXCL10, CXCL11, CX3CL1, CCL5, and
      CCL20 and the adhesion molecules intercellular adhesion molecule-1 and vascular
      cell adhesion molecule-1 (P < .05). DEPTOR siRNA-transfected ECs also bound
      increased numbers of peripheral blood mononuclear cells (P < .005) and CD3+ T
      cells (P < .005) in adhesion assays in vitro and had increased migration and
      angiogenic responses in spheroid sprouting (P < .01) and wound healing (P < .01)
      assays. Collectively, these findings define DEPTOR as a critical upstream
      regulator of EC activation responses and suggest that it plays an important role
      in endogenous mechanisms of anti-inflammation and pro-resolution.

PMID- 23881918
TI  - The paradox of the paroxysm: can seizure precipitants help explain human
      ictogenesis?
AB  - An epileptic brain is permanently in a diseased state, but seizures occur rarely
      and without warning. Here we examine this paradox, common to paroxysmal diseases.
      We review the problem in the context of the prototypic acquired epilepsies of the
      medial temporal lobe. We ask how an epileptic temporal lobe differs from a
      healthy one and examine biological mechanisms that may explain the transition to
      seizure. Attempts to predict seizure timing from analyses of brain electrical
      activity suggest that the neurological processes involved may be initiated
      significantly before a seizure. Furthermore, whereas seizures are said to occur
      without warning, some patients say they know when a seizure is imminent. Several
      factors, including sleep deprivation, oscillations in hormonal levels, or
      withdrawal from drugs, increase the probability of a seizure. We ask whether
      these seizure precipitants might act through common neuronal mechanisms. Several
      precipitating factors seem to involve relief from a neurosteroid modulation of
      gamma-amino butyric acid receptor type A (GABAA) receptors. We propose tests of
      this hypothesis. 

PMID- 23881916
TI  - Loss of the F-BAR protein CIP4 reduces platelet production by impairing membrane
      cytoskeleton remodeling.
AB  - Megakaryocytes generate platelets through extensive reorganization of the
      cytoskeleton and plasma membrane. Cdc42 interacting protein 4 (CIP4) is an F-BAR
      protein that localizes to membrane phospholipids through its BAR domain and
      interacts with Wiskott-Aldrich Syndrome Protein (WASP) via its SRC homology 3
      domain. F-BAR proteins promote actin polymerization and membrane tubulation. To
      study its function, we generated CIP4-null mice that displayed thrombocytopenia
      similar to that of WAS(-) mice. The number of megakaryocytes and their
      progenitors was not affected. However, the number of proplatelet protrusions was
      reduced in CIP4-null, but not WAS(-), megakaryocytes. Electron micrographs of
      CIP4-null megakaryocytes showed an altered demarcation membrane system. Silencing
      of CIP4, not WASP, expression resulted in fewer proplatelet-like extensions.
      Fluorescence anisotropy studies showed that loss of CIP4 resulted in a more rigid
      membrane. Micropipette aspiration demonstrated decreased cortical actin tension
      in megakaryocytic cells with reduced CIP4 or WASP protein. These studies support
      a new biophysical mechanism for platelet biogenesis whereby CIP4 enhances the
      complex, dynamic reorganization of the plasma membrane (WASP independent) and
      actin cortex network (as known for WASP and cortical actin) to reduce the work
      required for generating proplatelets. CIP4 is a new component in the highly
      coordinated system of megakaryocytic membrane and cytoskeletal remodeling
      affecting platelet production.

PMID- 23881917
TI  - Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute
      lymphoblastic leukemia.
AB  - The response of Philadelphia chromosome (Ph(+)) acute lymphoblastic leukemia
      (ALL) to treatment by BCR-ABL tyrosine kinase inhibitors (TKIs) has been
      disappointing, often resulting in short remissions typified by rapid outgrowth of
      drug-resistant clones. Therefore, new treatments are needed to improve outcomes
      for Ph(+) ALL patients. In a mouse model of Ph(+) B-lineage ALL, MCL-1 expression
      is dysregulated by the BCR-ABL oncofusion protein, and TKI treatment results in
      loss of MCL-1 expression prior to the induction of apoptosis, suggesting that MCL
      1 may be an essential prosurvival molecule. To test this hypothesis, we developed
      a mouse model in which conditional allele(s) of Mcl-1 can be deleted either
      during leukemia transformation or later after the establishment of leukemia. We
      report that endogenous MCL-1's antiapoptotic activity promotes survival during
      BCR-ABL transformation and in established BCR-ABL(+) leukemia. This requirement
      for MCL-1 can be overcome by overexpression of other antiapoptotic molecules. We
      further demonstrate that strategies to inhibit MCL-1 expression potentiate the
      proapoptotic action of BCL-2 inhibitors in both mouse and human BCR-ABL(+)
      leukemia cell lines. Thus, strategies focused on antagonizing MCL-1 function and
      expression would be predicted to be effective therapeutic strategies. 

PMID- 23881919
TI  - Astrocytes: new targets of melanocortin 4 receptor actions.
AB  - Astrocytes exert a wide variety of functions with paramount importance in brain
      physiology. After injury or infection, astrocytes become reactive and they
      respond by producing a variety of inflammatory mediators that help maintain brain
      homeostasis. Loss of astrocyte functions as well as their excessive activation
      can contribute to disease processes; thus, it is important to modulate reactive
      astrocyte response. Melanocortins are peptides with well-recognized anti
      inflammatory and neuroprotective activity. Although melanocortin efficacy was
      shown in systemic models of inflammatory disease, mechanisms involved in their
      effects have not yet been fully elucidated. Central anti-inflammatory effects of
      melanocortins and their mechanisms are even less well known, and, in particular,
      the effects of melanocortins in glial cells are poorly understood. Of the five
      known melanocortin receptors (MCRs), only subtype 4 is present in astrocytes.
      MC4R has been shown to mediate melanocortin effects on energy homeostasis,
      reproduction, inflammation, and neuroprotection and, recently, to modulate
      astrocyte functions. In this review, we will describe MC4R involvement in anti
      inflammatory, anorexigenic, and anti-apoptotic effects of melanocortins in the
      brain. We will highlight MC4R action in astrocytes and discuss their possible
      mechanisms of action. Melanocortin effects on astrocytes provide a new means of
      treating inflammation, obesity, and neurodegeneration, making them attractive
      targets for therapeutic interventions in the CNS. 

PMID- 23881921
TI  - Serum miR-1290 as a marker of pancreatic cancer--response.

PMID- 23881922
TI  - DNA methylation of the SLC16A3 promoter regulates expression of the human lactate
      transporter MCT4 in renal cancer with consequences for clinical outcome.
AB  - PURPOSE: The monocarboxylate transporter 4 (MCT4) is a metabolic target in tumor
      biology because it mediates lactate transport across membranes resulting in
      antiapoptotic effects. Cell experiments support the importance of MCT4 in clear
      cell renal cell carcinoma (ccRCC). In this study, we assessed the prognostic
      potential of MCT4 expression in ccRCC and its epigenetic regulation by DNA
      methylation as novel predictive marker for patient outcome using independent
      ccRCC cohorts. EXPERIMENTAL DESIGN: MCT4 protein expression was quantified in 207
      ccRCC and corresponding nontumor tissues. Data of an independent ccRCC cohort
      from The Cancer Genome Atlas (TCGA) were analyzed on MCT4 mRNA (n = 482) and DNA
      methylation (n = 283) level. The findings on MCT4 expression and DNA methylation
      in the SLC16A3 promoter were validated in a third cohort (n = 64). Promoter
      activity assays were conducted in four RCC cell lines. RESULTS: MCT4 protein
      expression was upregulated (P < 0.0001) in ccRCC and showed significant
      association with cancer-related death. Upregulation of MCT4 mRNA expression (P <
      0.00001) was confirmed in the TCGA cohort. Single CpG sites correlated inversely
      with mRNA expression and were associated with overall survival in Kaplan-Meier
      analyses [HR = 0.39; 95% confidence interval (CI), 0.24-0.64; P[log-rank] =
      1.23e(-04)]. Promoter activity studies confirmed MCT4 regulation by DNA
      methylation. The significant correlation between MCT4 protein and gene expression
      or DNA methylation at single CpG sites was validated in a third cohort. Again,
      higher methylation at individual CpG sites was associated with prolonged survival
      [HR = 0.05; 95% CI, 0.01-0.40; P[log-rank] = 6.91e(-05)]. CONCLUSION: We
      identified SLC16A3 promoter DNA methylation as a novel epigenetic mechanism for
      MCT4 regulation in ccRCC with first evidence of a biological rationale for
      prognosis and clinical outcome.

PMID- 23881923
TI  - BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human
      cancers with DNA repair deficiency.
AB  - PURPOSE: PARP1/2 inhibitors are a class of anticancer agents that target tumor
      specific defects in DNA repair. Here, we describe BMN 673, a novel, highly potent
      PARP1/2 inhibitor with favorable metabolic stability, oral bioavailability, and
      pharmacokinetic properties. EXPERIMENTAL DESIGN: Potency and selectivity of BMN
      673 was determined by biochemical assays. Anticancer activity either as a single
      agent or in combination with other antitumor agents was evaluated both in vitro
      and in xenograft cancer models. RESULTS: BMN 673 is a potent PARP1/2 inhibitor
      (PARP1 IC50 = 0.57 nmol/L), but it does not inhibit other enzymes that we have
      tested. BMN 673 exhibits selective antitumor cytotoxicity and elicits DNA repair
      biomarkers at much lower concentrations than earlier generation PARP1/2
      inhibitors (such as olaparib, rucaparib, and veliparib). In vitro, BMN 673
      selectively targeted tumor cells with BRCA1, BRCA2, or PTEN gene defects with 20-
      to more than 200-fold greater potency than existing PARP1/2 inhibitors. BMN 673
      is readily orally bioavailable, with more than 40% absolute oral bioavailability
      in rats when dosed in carboxylmethyl cellulose. Oral administration of BMN 673
      elicited remarkable antitumor activity in vivo; xenografted tumors that carry
      defects in DNA repair due to BRCA mutations or PTEN deficiency were profoundly
      sensitive to oral BMN 673 treatment at well-tolerated doses in mice. Synergistic
      or additive antitumor effects were also found when BMN 673 was combined with
      temozolomide, SN38, or platinum drugs. CONCLUSION: BMN 673 is currently in early
      phase clinical development and represents a promising PARP1/2 inhibitor with
      potentially advantageous features in its drug class.

PMID- 23881925
TI  - Protein kinase C-delta-mediated recycling of active KIT in colon cancer.
AB  - PURPOSE: Abnormal signaling through receptor tyrosine kinase (RTK) moieties is
      important in tumorigenesis and drug targeting of colorectal cancers. Wild-type
      KIT (WT-KIT), a RTK that is activated upon binding with stem cell factor (SCF),
      is highly expressed in some colon cancers; however, little is known about the
      functional role of SCF-dependent KIT activation in colon cancer pathogenesis. We
      aimed to elucidate the conditions and roles of WT-KIT activation in colon cancer
      tumorigenesis. EXPERIMENTAL DESIGN: Colorectal cancers with KIT expression were
      characterized by immunoblotting and immunohistochemistry. The biologic
      alterations after KIT-SCF binding were analyzed with or without protein kinase C
      (PKC) activation. RESULTS: We found that WT-KIT was expressed in a subset of
      colon cancer cell lines and was activated by SCF, leading to activation of
      downstream AKT and extracellular signal-regulated kinase (ERK) signaling
      pathways. We also showed that KIT expression gradually decreased, after prolonged
      SCF stimulation, due to lysosomal degradation. Degradation of WT-KIT after SCF
      binding was significantly rescued when PKC was activated. We also showed the
      involvement of activated PKC-delta in the recycling of WT-KIT. We further showed
      that a subset of colorectal cancers exhibit expressions of both WT-KIT and
      activated PKC-delta and that expression of KIT is correlated with poor patient
      survival (P = 0.004). CONCLUSIONS: Continuous downstream signal activation after
      KIT-SCF binding is accomplished through PKC-delta-mediated recycling of KIT. This
      sustained KIT activation may contribute to tumor progression in a subset of colon
      cancers with KIT expression and might provide the rationale for a therapeutic
      approach targeting KIT.

PMID- 23881924
TI  - New strategies in pediatric gliomas: molecular advances in pediatric low-grade
      gliomas as a model.
AB  - Pediatric low-grade gliomas (pLGG) account for more brain tumors in children than
      any other histologic subtype. While surgery, chemotherapy and radiation remain
      the mainstay of upfront treatment, recent advances in molecular interrogation of
      pLGG have shown a small number of recurring genetic mutations in these tumors
      that might be exploited therapeutically. Notable findings include abnormalities
      in the RAS/MAP kinase pathway such as NF-1 loss or BRAF activation and mTOR
      activation. Recent identification of activating re-arrangements in c-MYB and
      MYBL1 in pediatric diffuse astrocytoma also provide candidates for therapeutic
      intervention. Targeting these molecularly identified pathways may allow for
      improved outcomes for patients as pediatric oncology moves into the era of
      biology-driven medicine.

PMID- 23881926
TI  - Phase III trials of targeted anticancer therapies: redesigning the concept.
AB  - Randomized phase III trials provide the gold-standard evidence for the approval
      of new drugs: an experimental treatment is compared with the current standard of
      care to identify clinically relevant differences in a predefined endpoint.
      However, there are several problems relating to the current role of phase III
      trials in drug development including the limited clinical benefit observed for
      some approved agents, the necessity for large trials to detect these differences,
      the inability of such trials to identify rare but important toxicities, and high
      cost. The design of phase III trials evaluating drug combinations, and those
      including biomarkers, presents additional challenges. Here, we review these
      problems and suggest that phase III trials with adaptive designs in selected
      prescreened populations could reduce these limitations.

PMID- 23881927
TI  - Perioperative influenza vaccination reduces postoperative metastatic disease by
      reversing surgery-induced dysfunction in natural killer cells.
AB  - PURPOSE: Surgical removal of solid primary tumors is an essential component of
      cancer treatment. Surgery-induced dysfunction in natural killer (NK) cells has
      been linked to the development of metastases in animal models and patients with
      cancer. We investigated the activation of NK cells using influenza vaccine in the
      perioperative period to eradicate micrometastatic disease. EXPERIMENTAL DESIGN:
      Both the B16lacZ and 4T1 tumor models in immunocompetent mice were used to assess
      the in vivo efficacy of perioperative influenza vaccine administration. In
      healthy human donors and cancer surgery patients, we assessed NK cell function
      pre- and post-influenza vaccination using both in vivo and ex vivo assays.
      RESULTS: Using the TLR3 agonist poly(I:C), we showed as proof-of-principle that
      perioperative administration of a nonspecific innate immune stimulant can inhibit
      surgery-induced dysfunction in NK cells and attenuate metastases. Next, we
      assessed a panel of prophylactic vaccines for NK cell activation and determined
      that inactivated influenza vaccine was the best candidate for perioperative
      administration. Perioperative influenza vaccine significantly reduced tumor
      metastases and improved NK cytotoxicity in preclinical tumor models.
      Significantly, IFNalpha is the main cytokine mediator for the therapeutic effect
      of influenza vaccination. In human studies, influenza vaccine significantly
      enhanced NK cell activity in healthy human donors and cancer surgery patients.
      CONCLUSION: These results provide the preclinical rationale to pursue future
      clinical trials of perioperative NK cell activation, using vaccination in cancer
      surgery patients. Research into perioperative immune therapy is warranted to
      prevent immune dysfunction following surgery and eradicate metastatic disease.

PMID- 23881928
TI  - A purine scaffold HSP90 inhibitor BIIB021 has selective activity against KSHV
      associated primary effusion lymphoma and blocks vFLIP K13-induced NF-kappaB.
AB  - PURPOSE: Kaposi sarcoma-associated herpes virus (KSHV)-associated primary
      effusion lymphomas (PEL) have extremely poor prognosis when treated with
      conventional chemotherapy. KSHV-encoded viral FLICE-inhibitory protein (vFLIP)
      K13 binds to the IkappaB kinase (IKK) complex to constitutively activate the NF
      kappaB pathway, which has been shown to be essential for the survival and
      proliferation of PEL cells. The molecular chaperone HSP90 is a component of the
      IKK complex and is required for its activity. EXPERIMENTAL DESIGN: We have
      analyzed the effect of HSP90 inhibitors on the survival and proliferation of PEL
      cells and on the activity of the NF-kappaB pathway. RESULTS: We show that
      BIIB021, a purine scaffold-based orally administrable HSP90 inhibitor, shows
      preferential cytotoxicity toward PEL cells as compared with non-PEL cells. The
      cytotoxic effect of BIIB021 against PEL was associated with induction of cell
      cycle arrest and apoptosis. BIIB021 blocked the expression of a number of
      cellular proteins involved in the regulation of cell cycle and apoptosis. BIIB021
      also blocked constitutive NF-kappaB activity present in PEL cells, in part, by
      blocking the interaction of vFLIP K13 with the IKK complex subunits. In a
      xenograft model of PEL, BIIB021 significantly reduced tumor growth. CONCLUSION:
      BIIB021 blocks constitutive NF-kappaB activity in PEL and shows preferential
      antitumor activity against PEL in vitro and in vivo. BIIB021 may be a promising
      agent for treatment of PEL.

PMID- 23881929
TI  - The role of aberrant VHL/HIF pathway elements in predicting clinical outcome to
      pazopanib therapy in patients with metastatic clear-cell renal cell carcinoma.
AB  - PURPOSE: Inactivation of von Hippel-Lindau (VHL) gene in clear-cell renal cell
      carcinoma (RCC) leads to increased levels of hypoxia-inducible factors (HIF) and
      overexpression of HIF target genes, such as VEGF and others. VEGF-targeted agents
      are standard in advanced clear-cell RCC but biomarkers of activity are lacking.
      EXPERIMENTAL DESIGN: We analyzed tumor tissue samples from metastatic clear-cell
      RCC patients who received pazopanib as part of clinical trial VEG102616. We
      evaluated several components of the VHL/HIF pathway: VHL gene inactivation
      (mutation and/or methylation), HIF-1alpha and HIF-2alpha immunohistochemistry
      staining, and HIF-1alpha transcriptional signature. We evaluated the association
      of these biomarkers with best overall response rate (ORR) and progression-free
      survival (PFS) to pazopanib, a standard first-line VEGF-targeted agent. RESULTS:
      The VEG102616 trial enrolled 225 patients, from whom 78 samples were available
      for tumor DNA extraction. Of these, 70 patients had VHL mutation or methylation.
      VHL gene status did not correlate with ORR or PFS. Similarly, HIF-1alpha (65
      samples) and HIF-2alpha (66 samples) protein levels (high vs. low) did not
      correlate with ORR or PFS to pazopanib. The HIF-1alpha transcriptional signature
      (46 samples) was enriched in tumors expressing high HIF-1alpha levels. However,
      the HIF-1alpha gene expression signature was not associated with clinical outcome
      to pazopanib. CONCLUSIONS: In patients with advanced clear-cell RCC, several
      potential biomarkers along the VHL/HIF-1alpha/HIF-2alpha axis were not found to
      be predictive for pazopanib activity. Additional efforts must continue to
      identify biomarkers associated with clinical outcome to VEGF-targeted agents in
      metastatic RCC.

PMID- 23881930
TI  - Unhealthy behaviours and disability in older adults: three-City Dijon cohort
      study.
AB  - OBJECTIVES: To examine the individual and combined associations of unhealthy
      behaviours (low/intermediate physical activity, consuming fruit and vegetables
      less than once a day, current smoking/short term ex-smoking, never/former/heavy
      alcohol drinking), assessed at start of follow-up, with hazard of disability
      among older French adults and to assess the role of potential mediators, assessed
      repeatedly, of these associations. DESIGN: Population based cohort study.
      SETTING: Dijon centre of Three-City study. PARTICIPANTS: 3982 (2410 (60.5%)
      women) French community dwellers aged 65 or over included during 1999-2001;
      participants were disability-free at baseline when health behaviours were
      assessed. MAIN OUTCOME MEASURE: Hierarchical indicator of disability (no, light,
      moderate, severe) combining data from three disability scales (mobility,
      instrumental activities of daily living, basic activities of daily living)
      assessed five times between 2001 and 2012. RESULTS: During the 12 year follow-up,
      1236 participants (861 (69.7%) women) developed moderate or severe disability.
      Interval censored survival analyses (adjusted for age, sex, marital status, and
      education) showed low/intermediate physical activity (hazard ratio 1.72, 95%
      confidence interval 1.48 to 2.00), consuming fruit and vegetables less than once
      a day (1.24, 1.10 to 1.41), and current smoking/short term ex-smoking (1.26, 1.05
      to 1.50) to be independently associated with an increased hazard of disability,
      whereas no robust association with alcohol consumption was found. The hazard of
      disability increased progressively with the number of unhealthy behaviours
      independently associated with disability (P<0.001); participants with three
      unhealthy behaviours had a 2.53 (1.86 to 3.43)-fold increased hazard of
      disability compared with those with none. Reverse causation bias was verified by
      excluding participants who developed disability in the first four years of follow
      up; these analyses on 890 disability events yielded results similar to those in
      the main analysis. 30.5% of the association between the unhealthy behaviours
      score and disability was explained by body mass index, cognitive function,
      depressive symptoms, trauma, chronic conditions, and cardiovascular disease and
      its risk factors; the main contributors were chronic conditions and, to a lesser
      extent, depressive symptoms, trauma, and body mass index. CONCLUSIONS: An
      unhealthy lifestyle is associated with greater hazard of incident disability, and
      the hazard increases progressively with the number of unhealthy behaviours.
      Chronic conditions, depressive symptoms, trauma, and body mass index partially
      explained this association.

PMID- 23881931
TI  - Tranexamic acid in trauma: we need stronger global health policy.

PMID- 23881932
TI  - Regulatory forum opinion piece*: supporting the need for international
      harmonization of safety assessments for food flavoring substances.
AB  - The advancement of technology and the growth of international commerce underscore
      the need for global harmonization of regulatory safety requirements and their
      assessment pertaining to consumer products such as drugs, medical devices, and
      food. This need is particularly relevant when safety requirements involve time
      intensive and costly animal safety studies. Here we present the current
      regulatory requirements in Europe, the United States, and Japan for flavoring
      substances (FSs) used in foods and point out significant differences relevant to
      the international standardization for safety assessments that in our opinion need
      to be addressed and overcome. The safety assessments that are carried out for FSs
      in various countries are influenced by divergent definitions of FS, by the
      information required and available for regulatory submission, and by different
      regulatory procedures, including the use of decision tree approaches. The
      European Food Safety Authority (EFSA), the Expert Panel of the U.S. Flavor and
      Extract Manufacturers Association (FEMA), and the Joint Food and Agriculture
      Organization (FAO)/World Health Organization (WHO) Expert Committee on Food
      Additives (JECFA) are making efforts to improve and harmonize the safety
      assessment of FSs. The application of in silico methods such as quantitative
      structure-activity relationships and read-across strategies relying on expert
      input are useful as a first-step screening of the assessment. Application of the
      Threshold of Toxicological Concern (TTC) approach permits conclusions that are
      compatible with the risk assessment approaches currently used by international
      advisory committees. The Japanese Regulatory Authority, on the other hand, does
      not yet consider in silico methods but still requires in vivo and in vitro
      genotoxicity test data as well as repeat-dose 90-day toxicity data in at least
      one species, to be submitted as the first step in the safety assessment of FSs.
      With this article, we echo requests that have been made for xenobiotics by the
      pharmaceutical industry worldwide, extending them to food-related products,
      especially FSs. We encourage regulatory agencies to adopt globally harmonized
      safety assessment procedures, regulatory guidelines, and review practices for FSs
      to foster global trade and to reduce costs and laboratory animal use.

PMID- 23881934
TI  - Work flow analysis of around-the-clock processing of blood culture samples and
      integrated MALDI-TOF mass spectrometry analysis for the diagnosis of bloodstream
      infections.
AB  - BACKGROUND: Because sepsis has a high mortality rate, rapid microbiological
      diagnosis is required to enable efficient therapy. The effectiveness of MALDI-TOF
      mass spectrometry (MALDI-TOF MS) analysis in reducing turnaround times (TATs) for
      blood culture (BC) pathogen identification when available in a 24-h hospital
      setting has not been determined. METHODS: On the basis of data from a total
      number of 912 positive BCs collected within 140 consecutive days and work flow
      analyses of laboratory diagnostics, we evaluated different models to assess the
      TATs for batch-wise and for immediate response (real-time) MALDI-TOF MS pathogen
      identification of positive BC results during the night shifts. The results were
      compared to TATs from routine BC processing and biochemical identification
      performed during regular working hours. RESULTS: Continuous BC incubation
      together with batch-wise MALDI-TOF MS analysis enabled significant reductions of
      up to 58.7 h in the mean TATs for the reporting of the bacterial species. The TAT
      of batch-wise MALDI-TOF MS analysis was inferior by a mean of 4.9 h when compared
      to the model of the immediate work flow under ideal conditions with no
      constraints in staff availability. CONCLUSIONS: Together with continuous
      cultivation of BC, the 24-h availability of MALDI-TOF MS can reduce the TAT for
      microbial pathogen identification within a routine clinical laboratory setting.
      Batch-wise testing of positive BC loses a few hours compared to real-time
      identification but is still far superior to classical BC processing. Larger
      prospective studies are required to evaluate the contribution of rapid around-the
      clock pathogen identification to medical decision-making for septicemic patients.

PMID- 23881933
TI  - Delineating the genetic heterogeneity of ALS using targeted high-throughput
      sequencing.
AB  - BACKGROUND: Over 100 genes have been implicated in the aetiology of amyotrophic
      lateral sclerosis (ALS). A detailed understanding of their independent and
      cumulative contributions to disease burden may help guide various clinical and
      research efforts. METHODS: Using targeted high-throughput sequencing, we
      characterised the variation of 10 Mendelian and 23 low penetrance/tentative ALS
      genes within a population-based cohort of 444 Irish ALS cases (50 fALS, 394 sALS)
      and 311 age-matched and geographically matched controls. RESULTS: Known or
      potential high-penetrance ALS variants were identified within 17.1% of patients
      (38% of fALS, 14.5% of sALS). 12.8% carried variants of Mendelian disease genes
      (C9orf72 8.78%; SETX 2.48%; ALS2 1.58%; FUS 0.45%; TARDBP 0.45%; OPTN 0.23%; VCP
      0.23%. ANG, SOD1, VAPB 0%), 4.7% carried variants of low penetrance/tentative ALS
      genes and 9.7% (30% of fALS, 7.1% of sALS) carried previously described ALS
      variants (C9orf72 8.78%; FUS 0.45%; TARDBP 0.45%). 1.6% of patients carried
      multiple known/potential disease variants, including all identified carriers of
      an established ALS variant (p<0.01); TARDBP:c.859G>A(p.[G287S]) (n=2/2 sALS).
      Comparison of our results with those from studies of other European populations
      revealed significant differences in the spectrum of disease variation (p=1.7*10(
      4)). CONCLUSIONS: Up to 17% of Irish ALS cases may carry high-penetrance variants
      within the investigated genes. However, the precise nature of genetic
      susceptibility differs significantly from that reported within other European
      populations. Certain variants may not cause disease in isolation and concomitant
      analysis of disease genes may prove highly important.

PMID- 23881935
TI  - Duration of obesity linked with coronary artery calcification.

PMID- 23881936
TI  - Gastric estradiol-17beta (E2) and liver ERalpha correlate with serum E2 in the
      cholestatic male rat.
AB  - Cholestasis is associated with changes in hepatic cholesterol metabolism and
      serum estrogen levels. Ueyama and colleagues reported that the gastric estradiol
      17beta (E2) level in the portal vein is several times higher than that in the
      artery. This study aimed to clarify the relationships between gastric E2, hepatic
      estrogen receptor (ER) alpha and cholesterol metabolism in cholestatic male rats
      induced by bile duct ligation (BDL). After BDL, serum E2 levels in the portal
      vein and artery were measured by ELISA. The gene expression of gastric estrogen
      synthesizing enzymes and various hepatic enzymes for cholesterol metabolism were
      measured by real-time RT-PCR, and gastric aromatase and hepatic ERalpha proteins
      were determined by immunohistochemistry and western blotting. Portal E2 levels
      increased by 4.9, 5.0, and 3.6 times that of controls at 2 days after BDL
      (BDL2d), BDL4d, and BDL7d respectively. The change in arterial E2 levels was
      positively correlated with that in the portal vein. Under these conditions, the
      expression of hepatic Ers1 (ERalpha) mRNA and protein was significantly reduced
      in a negative correlation with serum E2 levels in the portal vein after BDL. The
      expression of hepatic male-specific cytochrome P450 (CYP) genes Cyp2c55 and
      Cyp3a2 decreased and female-specific Cyp2c12 increased after BDL. It is
      postulated that the increase in gastric E2 levels, which occurs after BDL,
      results in the reduction of hepatic ERalpha, the elevation of arterial E2 level
      and leads to cholesterol metabolism becoming sex steroid dependent. 

PMID- 23881937
TI  - Mice deficient in PAPP-A show resistance to the development of diabetic
      nephropathy.
AB  - We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic
      nephropathy. Normal human kidney showed specific staining for PAPP-A in
      glomeruli, and this staining was markedly increased in diabetic kidney. To assess
      the possible contribution of PAPP-A in the development of diabetic nephropathy,
      we induced diabetes with streptozotocin in 14-month-old WT and Papp-A knockout
      (KO) mice. Renal histopathology was evaluated after 4 months of stable
      hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities
      including thickening of Bowman's capsule (100% of mice), increased glomerular
      size (80% of mice), tubule dilation (80% of mice), and mononuclear cell
      infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had
      similar evidence of tubule dilation and mononuclear cell infiltration to those of
      diabetic WT mice, indicating that these changes were predominantly age-related.
      However, thickened Bowman's capsule and increased glomerular size appeared
      specific for the experimental diabetes. Kidneys from diabetic Papp-A KO mice had
      significantly reduced or no evidence of changes in Bowman's capsule thickening
      and glomerular size. There was also a shift to larger mesangial area and
      increased macrophage staining in diabetic WT mice compared with Papp-A KO mice.
      In summary, elevated PAPP-A expression in glomeruli is associated with diabetic
      nephropathy in humans and absence of PAPP-A is associated with resistance to the
      development of indicators of diabetic nephropathy in mice. These data suggest
      PAPP-A as a potential therapeutic target for diabetic nephropathy. 

PMID- 23881938
TI  - Helicase activation and establishment of replication forks at chromosomal origins
      of replication.
AB  - Many replication proteins assemble on the pre-RC-formed replication origins and
      constitute the pre-initiation complex (pre-IC). This complex formation
      facilitates the conversion of Mcm2-7 in the pre-RC to an active DNA helicase, the
      Cdc45-Mcm-GINS (CMG) complex. Two protein kinases, cyclin-dependent kinase (CDK)
      and Dbf4-dependent kinase (DDK), work to complete the formation of the pre-IC.
      Each kinase is responsible for a distinct step of the process in yeast; Cdc45
      associates with origins in a DDK-dependent manner, whereas the association of
      GINS with origins depends on CDK. These associations with origins also require
      specific initiation proteins: Sld3 for Cdc45; and Dpb11, Sld2, and Sld3 for GINS.
      Functional homologs of these proteins exist in metazoa, although pre-IC formation
      cannot be separated by requirement of DDK and CDK because of experimental
      limitations. Once the replicative helicase is activated, the origin DNA is
      unwound, and bidirectional replication forks are established. 

PMID- 23881939
TI  - Replication-fork dynamics.
AB  - The proliferation of all organisms depends on the coordination of enzymatic
      events within large multiprotein replisomes that duplicate chromosomes. Whereas
      the structure and function of many core replisome components have been clarified,
      the timing and order of molecular events during replication remains obscure. To
      better understand the replication mechanism, new methods must be developed that
      allow for the observation and characterization of short-lived states and dynamic
      events at single replication forks. Over the last decade, great progress has been
      made toward this goal with the development of novel DNA nanomanipulation and
      fluorescence imaging techniques allowing for the direct observation of
      replication-fork dynamics both reconstituted in vitro and in live cells. This
      article reviews these new single-molecule approaches and the revised
      understanding of replisome operation that has emerged. 

PMID- 23881940
TI  - Break-induced DNA replication.
AB  - Recombination-dependent DNA replication, often called break-induced replication
      (BIR), was initially invoked to explain recombination events in bacteriophage but
      it has recently been recognized as a fundamentally important mechanism to repair
      double-strand chromosome breaks in eukaryotes. This mechanism appears to be
      critically important in the restarting of stalled and broken replication forks
      and in maintaining the integrity of eroded telomeres. Although BIR helps preserve
      genome integrity during replication, it also promotes genome instability by the
      production of loss of heterozygosity and the formation of nonreciprocal
      translocations, as well as in the generation of complex chromosomal
      rearrangements. 

PMID- 23881941
TI  - Replication proteins and human disease.
AB  - In this article, we discuss the significance of DNA replication proteins in human
      disease. There is a broad range of mutations in genes encoding replication
      proteins, which result in several distinct clinical disorders that share common
      themes. One group of replication proteins, the MCMs, has emerged as effective
      biomarkers for early detection of a range of common cancers. They offer practical
      and theoretical advantages over other replication proteins and have been
      developed for widespread clinical use. 

PMID- 23881942
TI  - Archaeology of eukaryotic DNA replication.
AB  - Recent advances in the characterization of the archaeal DNA replication system
      together with comparative genomic analysis have led to the identification of
      several previously uncharacterized archaeal proteins involved in replication and
      currently reveal a nearly complete correspondence between the components of the
      archaeal and eukaryotic replication machineries. It can be inferred that the
      archaeal ancestor of eukaryotes and even the last common ancestor of all extant
      archaea possessed replication machineries that were comparable in complexity to
      the eukaryotic replication system. The eukaryotic replication system encompasses
      multiple paralogs of ancestral components such that heteromeric complexes in
      eukaryotes replace archaeal homomeric complexes, apparently along with
      subfunctionalization of the eukaryotic complex subunits. In the archaea,
      parallel, lineage-specific duplications of many genes encoding replication
      machinery components are detectable as well; most of these archaeal paralogs
      remain to be functionally characterized. The archaeal replication system shows
      remarkable plasticity whereby even some essential components such as DNA
      polymerase and single-stranded DNA-binding protein are displaced by unrelated
      proteins with analogous activities in some lineages. 

PMID- 23881944
TI  - An introduction to patient decision aids.

PMID- 23881943
TI  - The minichromosome maintenance replicative helicase.
AB  - The eukaryotic replicative helicase, the minichromosome maintenance (MCM)
      complex, is composed of six distinct, but related, subunits MCM(2-7). The
      relationship between the sequences of the subunits indicates that they are
      derived from a common ancestor and indeed, present-day archaea possess a
      homohexameric MCM. Recent progress in the biochemical and structural studies of
      both eukaryal and archaeal MCM complexes are beginning to shed light on the
      mechanisms of action of this key component of the replisome. 

PMID- 23881945
TI  - Lisfranc injuries.

PMID- 23881946
TI  - Unintended consequences of sanctions against Iran.

PMID- 23881947
TI  - Global burden of sickle cell anaemia is set to rise by a third by 2050.

PMID- 23881948
TI  - Avastin is as effective as Lucentis in treating wet age related macular
      degeneration, study finds.

PMID- 23881949
TI  - GSK's head of finance in China is banned from leaving the country.

PMID- 23881950
TI  - Injuries to health workers are common but safety checks are rare, report finds.

PMID- 23881951
TI  - Visual search with negative slopes: the statistical power of numerosity guides
      attention.
AB  - Four experiments were performed to examine the hypothesis that abstract,
      nonspatial, statistical representations of object numerosity can be used for
      attentional guidance in a feature search task. Participants searched for an odd
      colored target among distractors of one, two, or three other colors. An enduring
      advantage of large over small sets (i.e., negative slopes of search functions)
      was found, and this advantage grew with the number of colored subsets among
      distractors. The results of Experiments 1 and 2 showed that the negative slopes
      cannot be ascribed to the spatial grouping between distractors but can be
      partially explained by the spatial density of the visual sets. Hence, it appears
      that observers relied on numerosity of subsets to guide attention. Experiments 3a
      and 3b tested the processes within and between color subsets of distractors more
      precisely. It was found that the visual system collects numerosity statistics
      that can be used for guidance within each subset independently. However, each
      subset representation should be serially selected by attention. As attention
      shifts from one subset to another, the "statistical power" effects from every
      single subset are accumulated to provide a more pronounced negative slope.

PMID- 23881952
TI  - Statistical learning in the past modulates contextual cueing in the future.
AB  - Observers' capability to extract statistical regularities from the visual world
      can facilitate attentional orienting. For instance, visual search benefits from
      the repetition of target locations by means of probability learning. Furthermore,
      repeated (old) contexts of nontargets contribute to faster visual search in
      comparison to random (new) arrangements of nontargets. Chun and Jiang (1998)
      called this effect "contextual cueing" because old contexts provide spatial cues
      to repeated target locations. In the present study, we investigated how
      probability learning modulates the adaptation of contextual cueing to a change in
      target location. After an initial learning phase, targets were relocated within
      their respective contexts to new positions that were, however, familiar from
      previous presentations in other spatial contexts. Contextual cueing was observed
      for relocated targets that originated from old contexts, but it turned into costs
      when relocated targets had previously been presented in new contexts. Thus,
      probability learning was not sufficient to observe adaptive contextual cueing for
      relocated targets. Instead, the contextual past of target locations--whether they
      had been cued or not--modulated the integration of relocated targets into a
      learned context. These findings imply that observers extract multiple levels of
      available statistical information and use them to infer hypotheses about future
      occurrences of familiar stimuli.

PMID- 23881953
TI  - Taming neonatal hypoxic-ischemic brain injury by intranasal delivery of
      plasminogen activator inhibitor-1.
AB  - BACKGROUND AND PURPOSE: Plasminogen activator inhibitor-I (PAI-1), a ~50-kDa
      serine protease inhibitor, markedly reduces the extravascular toxicity of tissue
      type plasminogen activator in experimental hypoxic-ischemic (HI) brain injury of
      newborns. However, the current treatment with PAI-1 requires
      intracerebroventricle injection to cross the blood-brain barrier, which is an
      invasive procedure of limited clinical potential. Thus, we tested whether
      intranasal administration of PAI-1 can bypass blood-brain barrier and mitigate
      neonatal HI brain injury. METHODS: Rat pups were subjected to HI, with or without
      lipopolysaccharide pre-exposure, followed by intranasal delivery of a stable
      mutant form of PAI-1 (CPAI). RESULTS: Immunoblotting showed that CPAI
      sequentially entered the olfactory bulbs and cerebral cortex after intranasal
      delivery and reduced ~75% of brain atrophy in HI or lipopolysaccharide-sensitized
      HI injury. Mechanistically, CPAI attenuated HI-induced plasminogen activators and
      lipopolysaccharide/HI-induced nuclear factor-kappaB signaling, neuroinflammation,
      and blood-brain barrier permeability. CONCLUSIONS: Intranasal delivery of CPAI is
      an effective treatment of experimental HI brain injury of newborns. Clinical
      application of this experimental therapy merits further investigation.

PMID- 23881954
TI  - Smoking, heart rate, and ischemic stroke: a population-based prospective cohort
      study among Inner Mongolians in China.
AB  - BACKGROUND AND PURPOSE: Smoking is a major public health challenge and an
      important risk factor for cardiovascular diseases. No previous studies have
      evaluated the association among smoking, heart rate, and ischemic stroke in an
      Inner Mongolian population. We aim to evaluate the cumulative effect of smoking
      and heart rate on ischemic stroke incidence in this population. METHODS: A
      prospective cohort study from June 2003 through July 2012 was conducted among
      2530 people >=20 years of age from Inner Mongolia, China. We categorized the
      participants into 4 subgroups according to smoking status and heart rate. Cox
      proportional hazards models and receiver operating characteristic curves were
      used to evaluate the association among smoking, heart rate, and ischemic stroke.
      RESULTS: The multivariate-adjusted hazard ratios (95% confidence intervals) of
      ischemic stroke incidence for nonsmokers with heart rate >=80 bpm, smokers with
      heart rate <80 bpm, and smokers with heart rate >=80 bpm were 1.42 (0.62-3.28),
      2.11 (1.06-4.23), and 2.86 (1.33-6.14), respectively, compared with nonsmokers
      with heart rate <80 bpm. The area under receiver operating characteristic curve
      (area under the curve) for a model containing smoking status and heart rate,
      along with conventional factors (area under the curve=0.755), was significantly
      (P=0.018) larger than the one containing only conventional factors (area under
      the curve=0.739). CONCLUSIONS: Our study indicated that smoking was an
      independent risk factor of ischemic stroke, and smokers with faster heart rate
      had the highest risk of ischemic stroke among Inner Mongolians. These findings
      suggest that smoking status and heart rate may be valuable in predicting ischemic
      stroke incidence.

PMID- 23881955
TI  - The association between stroke, depression, and 5-year mortality among very old
      people.
AB  - BACKGROUND AND PURPOSE: Depression after stroke has been associated with
      increased mortality, but little is known about this association among very old
      people. METHODS: A population-based study among people >=85 years of age was
      conducted in northern Sweden and Finland, comprising cross-sectional assessments
      and subsequent survival data. The 452 individuals who had completed the Geriatric
      Depression Scale-15 assessment were selected. Depression was defined as a score
      of >=5 on the geriatric depression scale. RESULTS: Of those with a history of
      stroke, 38 of 88 (43.2%) people were depressed, and 11 of the 38 (28.9%) were
      treated with antidepressants, compared with 91 of 364 (25.0%) depressed (P=0.001)
      and 17 of 91 (18.7%) treated with antidepressants among those without stroke.
      Having a history of stroke and ongoing depression was associated with increased 5
      year mortality compared with having only stroke (hazard ratio, 1.90; confidence
      interval, 1.15-3.13), having only depression (hazard ratio, 1.59; confidence
      interval, 1.03-2.45), and compared with having neither stroke nor depression
      (hazard ratio, 2.50; confidence interval, 1.69-3.69). Having only stroke without
      depression did not increase mortality compared with having neither stroke nor
      depression. CONCLUSIONS: A history of stroke was associated with increased
      mortality among very old people but only among those who were also depressed.
      Depression seemed to be underdiagnosed and undertreated.

PMID- 23881956
TI  - Use of total cerebral blood flow as an imaging biomarker of known cardiovascular
      risks.
AB  - BACKGROUND AND PURPOSE: This study examined whether overall cerebral blood flow
      was associated with known vascular risk factors, including cardiometabolic risk
      factors that comprise the metabolic syndrome, carotid artery intima-media
      thickness, and the Framingham risk score. METHODS: Three separate samples were
      available for analysis. Two comparable samples were combined to form a primary
      sample of middle-aged participants (n=576; 30-55 years of age) that completed
      both a risk factor assessment and a resting brain scan. Samples were recruited
      via mailings and advertisements within an urban area. Quantitative measures of
      cerebral blood flow were derived from arterial spin-labeled MRI in this sample
      and in a validation/generalization sample (n=76; 30-55 years). RESULTS: Cerebral
      blood flow was inversely associated with cardiometabolic risk indices, that is,
      associated with lower waist circumference, systolic blood pressure, glucose, and
      triglyceride and high-density lipoprotein. Moreover, cerebral blood flow was also
      related to Framingham risk and carotid intima-media thickness. In the validation
      sample, which used a slightly different brain imaging technique, significant
      relationships were replicated for cardiometabolic risk, but not for Framingham
      risk. CONCLUSIONS: Reduced cerebral blood flow seems to be a correlate of
      vascular disease risk factors associated with cardiometabolic dysregulation.
      Cerebral blood flow may provide a valid imaging biomarker for cardiovascular
      risk.

PMID- 23881957
TI  - Age-related decline in oligodendrogenesis retards white matter repair in mice.
AB  - BACKGROUND AND PURPOSE: Aging is one of the major risk factors for white matter
      injury in cerebrovascular disease. However, the effects of age on the mechanisms
      of injury/repair in white matter remain to be fully elucidated. Here, we ask
      whether, compared with young brains, white matter regions in older brains may be
      more vulnerable in part because of decreased rates of compensatory
      oligodendrogenesis after injury. METHODS: A mouse model of prolonged cerebral
      hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month
      and 8-month-old mice. Matching in vitro studies were performed by subjecting
      oligodendrocyte precursor cells to sublethal 7-day CoCl2 treatment to induce
      chemical hypoxic stress. RESULTS: Baseline myelin density in the corpus callosum
      was similar in 2-month and 8-month-old mice. But after induction of prolonged
      cerebral hypoperfusion, older mice showed more severe white matter injury
      together with worse deficits in working memory. The numbers of newborn
      oligodendrocytes and their precursors were increased by cerebral hypoperfusion in
      young mice, whereas these endogenous responses were significantly dampened in
      older mice. Defects in cyclic AMP response element-binding protein signaling may
      be involved because activating cyclic AMP response element-binding protein with
      the type-III phosphodiesterase inhibitor cilostazol in older mice restored the
      differentiation of oligodendrocyte precursor cells, alleviated myelin loss, and
      improved cognitive dysfunction during cerebral hypoperfusion. Cell culture
      systems confirmed that cilostazol promoted the differentiation of oligodendrocyte
      precursor cells. CONCLUSIONS: An age-related decline in cyclic AMP response
      element-binding protein-mediated oligodendrogenesis may compromise endogenous
      white matter repair mechanisms, and therefore, drugs that activate cyclic AMP
      response element-binding protein signaling provide a potential therapeutic
      approach for treating white matter injury in aging brains.

PMID- 23881958
TI  - Extended-release niacin therapy and risk of ischemic stroke in patients with
      cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome
      with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH)
      trial.
AB  - BACKGROUND AND PURPOSE: In Atherothrombosis Intervention in Metabolic Syndrome
      with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH)
      trial, addition of extended-release niacin (ERN) to simvastatin in participants
      with established cardiovascular disease, low high-density lipoprotein
      cholesterol, and high triglycerides had no incremental benefit, despite increases
      in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete
      end point adjudication suggested increased ischemic stroke risk among
      participants randomized to ERN. METHODS: This final analysis was conducted after
      complete AIM-HIGH event ascertainment to further explore potential relationship
      between niacin therapy and ischemic stroke risk. RESULTS: There was no group
      difference in trial primary composite end point at a mean 36-month follow-up
      among 3414 patients (85% men; mean age, 64+/-9 years) randomized to simvastatin
      plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the
      intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18
      (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95%
      confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed
      independent associations between ischemic stroke risk and >65 years of age (HR,
      3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic
      attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline
      Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile;
      HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile;
      overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI,
      0.97-3.11; P=0.063). CONCLUSIONS: Although there were numerically more ischemic
      strokes with addition of ERN to simvastatin that reached nominal significance,
      the number was small, and multivariable analysis accounting for known risk
      factors did not support a significant association between niacin and ischemic
      stroke risk. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00120289.

PMID- 23881959
TI  - Cilostazol ameliorates warfarin-induced hemorrhagic transformation after cerebral
      ischemia in mice.
AB  - BACKGROUND AND PURPOSE: Although long-term treatment with the oral anticoagulant
      warfarin is widely used to prevent cardioembolic ischemic stroke, it has been
      reported that warfarin can exacerbate hemorrhagic transformation (HT) after
      cerebral ischemia. We investigated whether cilostazol, a phosphodiesterase-III
      inhibitor, suppressed the warfarin-induced HT after cerebral ischemia in mice.
      METHODS: Male ddY mice were treated with oral warfarin before 3-hour middle
      cerebral artery occlusion followed by 21-hour reperfusion to induce HT. The
      duration of warfarin pretreatment was determined by measurement of prothrombin
      time-international normalized ratio value. Cilostazol or vehicle was administered
      by intraperitoneal injection immediately after reperfusion. The infarct volume,
      brain swelling, and brain hemoglobin content were evaluated at 24 hours after
      middle cerebral artery occlusion. We also evaluated the survival rate of each
      treated group for 7 days after surgery. To investigate the mechanism underlying
      cilostazol's effects, the proteins involved in vascular endothelial integrity
      were investigated using Western blotting. RESULTS: HT volume was exacerbated by
      warfarin treatment, and cilostazol (3 mg/kg, i.p.) suppressed this exacerbation
      (sham, mean+/-SD, 29.2+/-13.4 mg/dL; vehicle, 33.3+/-11.9 mg/dL; warfarin,
      379.4+/-428.9 mg/dL; warfarin+cilostazol 1 mg/kg, 167.5+/-114.2 mg/dL;
      warfarin+cilostazol 3 mg/kg, 116.9+/-152.3 mg/dL). Furthermore, cilostazol
      improved survival rate and upregulated the expression of tight junction proteins
      and vascular endothelial cadherin. CONCLUSIONS: Cilostazol reduced the warfarin
      related risk of HT after ischemia by protecting the vascular endothelial cells.
      This result suggested that cilostazol administration in patients with acute
      ischemic stroke might reduce HT.

PMID- 23881960
TI  - Importance of cerebral artery recanalization in patients with stroke with and
      without neurological improvement after intravenous thrombolysis.
AB  - BACKGROUND AND PURPOSE: Recanalization status after intravenous thrombolysis
      (IVT) in patients with ischemic stroke is a reference point to proceed with a
      rescue reperfusion intervention, although early neurological improvement (NI) may
      preclude endovascular procedures. We aimed to evaluate the importance of
      restoration of blood flow at the arterial occlusion site in subgroups of patients
      with stroke stratified by early NI after IVT. METHODS: The following patients
      were recruited from the Safe Implementation of Treatment in Stroke-International
      Stroke Thrombolysis Register: (1) with baseline vessel occlusion documented by
      computed tomographic (CT) or magnetic resonance (MR) angiography and follow-up
      angioimaging between 22 and 36 hours after IVT available; and (2) with dense
      cerebral artery sign on admission CT scan and results of follow-up CT reported.
      Recanalization at 24 hours was defined as absence of vessel occlusion or as
      resolution of dense cerebral artery sign on follow-up 22- to 36-hour imaging. NI
      was assessed at 2 hours and 24 hours after IVT and was defined as improvement by
      20% from baseline National Institute of Health Stroke scale score. Primary
      outcome measure was independence, defined as modified Rankin scale score 0 to 2
      after 3 months. RESULTS: Of 28136 cases registered between December 2003 and
      November 2009, 5324 cases (19%) met the inclusion criteria. Patients with both NI
      at 2 hours post-treatment and vessel recanalization had the best chances to
      achieve independence at 3 months (adjusted odds ratio, 15.8; 95% confidence
      interval, 12.5-20.0), followed by those who had NI despite persistent occlusion
      (adjusted odds ratio, 4.7; 95% confidence interval, 3.6-6.1); and those without
      NI despite recanalization (adjusted odds ratio, 2.7; 95% confidence interval, 2.2
      3.3). CONCLUSIONS: Recanalization of an occluded artery in acute stroke is
      associated with favorable functional outcome both in patients with and without NI
      after IVT. In future evaluations of mechanical thrombectomy and other additional
      strategies, recanalization should be considered in patients with persisting
      occlusion after IVT even after significant NI.

PMID- 23881962
TI  - Primary care and population factors associated with NHS Health Check coverage: a
      national cross-sectional study.
AB  - INTRODUCTION: High and equitable coverage of systematic cardiovascular disease
      (CVD) prevention programmes, such as the NHS Health Check programme in England,
      is essential if they are to effectively reduce the population CVD burden.
      METHODS: We conducted a cross-sectional study using data from 151 English primary
      care trusts (PCTs) on NHS Health Check coverage during 2011-12. We examined the
      associations between programme coverage and primary care and population factors,
      including patient demographics, primary care workforce and cardiovascular health
      need. RESULTS: Median coverage of NHS Health Checks was 8.2%, with wide PCT-level
      variation (range = 0-29.8%). Coverage was significantly higher in PCTs in the
      most deprived areas compared with the least deprived (P = 0.035), adjusting for
      covariates. Significant negative associations between coverage and a higher
      proportion of PCT population aged 40-74 years-the eligible Health Check age
      group, a larger total population size and higher practice staffing levels were
      found in the unadjusted analyses. CONCLUSIONS: NHS Health Check coverage during
      2011-12 was lower than the government projection of 18% coverage. Coverage must
      be increased through concerted multi-disciplinary strategies, for the programme
      to improve cardiovascular health in England. Considerable variation in
      participation between PCTs warrants attention, with enhanced support for poor
      performers.

PMID- 23881961
TI  - 123I-iomazenil single photon emission computed tomography visualizes recovery of
      neuronal integrity by bone marrow stromal cell therapy in rat infarct brain.
AB  - BACKGROUND AND PURPOSE: This study was aimed to assess whether (123)I-iomazenil
      (IMZ) single photon emission computed tomography can serially monitor the effects
      of bone marrow stromal cell (BMSC) transplantation on neuronal integrity in
      infarct brain of rats. METHODS: The BMSCs were harvested from green fluorescent
      protein-transgenic rats and were cultured. The rats were subjected to permanent
      middle cerebral artery occlusion. Their motor function was serially quantified
      throughout the experiments. The BMSCs or vehicle was stereotactically
      transplanted into the ipsilateral striatum at 7 days after the insult. Using
      small-animal single photon emission computed tomography/computed tomography
      apparatus, the (123)I-IMZ uptake was serially measured at 6 and 35 days after the
      insult. Finally, fluorescence immunohistochemistry was performed to evaluate the
      distribution of engrafted cells and their phenotypes. RESULTS: The distribution
      of (123)I-IMZ was markedly decreased in the ipsilateral neocortex at 6 days
      postischemia. The vehicle-transplanted animals did not show a significant change
      at 35 days postischemia. However, BMSC transplantation significantly improved the
      distribution of (123)I-IMZ in the peri-infarct neocortex as well as motor
      function. The engrafted BMSCs were densely distributed around cerebral infarct,
      and some of them expressed neuronal nuclear antigen and gamma-aminobutyric acid
      type-A receptor. CONCLUSIONS: The present findings strongly suggest that the
      BMSCs may enhance functional recovery by improving the neuronal integrity in the
      peri-infarct area, when directly transplanted into the infarct brain at
      clinically relevant timing. (123)I-IMZ single photon emission computed tomography
      may be a promising modality to scientifically prove the beneficial effects of
      BMSC transplantation on the host brain in clinical situation.

PMID- 23881964
TI  - Implications of rising prediabetes prevalence.

PMID- 23881965
TI  - Novel forms of lipodystrophy: why should we care?

PMID- 23881966
TI  - Comparative effectiveness and the future of clinical research in diabetes.

PMID- 23881969
TI  - Dietary quality in adolescents with type 1 diabetes.

PMID- 23881967
TI  - Pancreas transplant alone: a procedure coming of age.
AB  - The goal of this review is to highlight the significant improvements, over the
      past four decades, in outcomes after a pancreas transplant alone (PTA) in
      patients with brittle diabetes and recurrent episodes of hypoglycemia and/or
      hypoglycemic unawareness. A successful PTA-in contrast to intensive insulin
      regimens and insulin pumps-restores normoglycemia without the risk of
      hypoglycemia and prevents, halts, or reverses the development or progression of
      secondary diabetes complications. In this International Pancreas Transplant
      Registry (IPTR) analysis, we reviewed the records of 1,929 PTA recipients from
      December 1966 to December 2011. We computed graft survival rates according to the
      Kaplan-Meier method and used uni- and multivariate analyses. In the most recent
      era (January 2007-December 2011), patient survival rates were >95% at 1 year
      posttransplant and >90% at 5 years. Graft survival rates with tacrolimus-based
      maintenance therapy were 86% at 1 year and 69% at 3 years and with sirolimus, 94
      and 84%. Graft survival rates have significantly improved owing to marked
      decreases in technical and immunologic graft failure rates (P < 0.05). As a
      result, the need for a subsequent kidney transplant has significantly decreased,
      over time, to only 6% at 5 years. With patient survival rates of almost 100% and
      graft survival rates of up to 94% at 1 year, a PTA is now a highly successful
      long-term option. It should be considered in nonuremic patients with brittle
      diabetes in order to achieve normoglycemia, to avoid hypoglycemia, and to prevent
      the development or progression of secondary diabetes complications. 

PMID- 23881970
TI  - Role of anti-phospholipase A(2) receptor antibodies in the differential diagnosis
      of diabetic and membranous nephropathy.

PMID- 23881971
TI  - Anti-pituitary antibodies and hypogonadotropic hypogonadism in type 2 diabetes:
      in search of a role.

PMID- 23881972
TI  - Sociodemographic variables for predicting diabetes in Panama.

PMID- 23881973
TI  - Sitagliptin improves postprandial hyperglycemia by inhibiting glucagon secretion
      in Werner syndrome with diabetes.

PMID- 23881974
TI  - Latent autoimmune diabetes in adults presenting as diabetes "recurrence" after
      bariatric surgery: a case report.

PMID- 23881975
TI  - Hypoglycemia in adults with cystic fibrosis during oral glucose tolerance
      testing.

PMID- 23881976
TI  - Comment on: Kan et al. A systematic review and meta-analysis of the association
      between depression and insulin resistance. Diabetes Care 2013;36:480-489.

PMID- 23881977
TI  - Response to Comment on: Kan et al. A systematic review and meta-analysis of the
      association between depression and insulin resistance. Diabetes Care 2013;36:480
      489.

PMID- 23881978
TI  - Comment on: Beverly et al. Do older adults aged 60-75 years benefit from diabetes
      behavioral interventions? Diabetes Care 2013;36:1501-1506.

PMID- 23881979
TI  - Response to Comment on: Beverly et al. Do older adults aged 60-75 years benefit
      from diabetes behavioral interventions? Diabetes Care 2013;36:1501-1506.

PMID- 23881980
TI  - Comment on: Black et al. The relative contribution of prepregnancy overweight and
      obesity, gestational weight gain, and IADPSG-defined gestational diabetes
      mellitus to fetal overgrowth. Diabetes Care 2013;36:56-62.

PMID- 23881981
TI  - Response to Comment on: Black et al. The relative contribution of prepregnancy
      overweight and obesity, gestational weight gain, and IADPSG-defined gestational
      diabetes mellitus to fetal overgrowth. Diabetes Care 2013;36:56-62.

PMID- 23881982
TI  - Comment on: Margolis et al. Lack of effectiveness of hyperbaric oxygen therapy
      for the treatment of diabetic foot ulcer and the prevention of amputation: a
      cohort study. Diabetes Care 2013;36:1961-1966.

PMID- 23881983
TI  - Comment on: Margolis et al. Lack of effectiveness of hyperbaric oxygen therapy
      for the treatment of diabetic foot ulcer and the prevention of amputation: a
      cohort study. Diabetes Care 2013;36:1961-1966.

PMID- 23881984
TI  - Comment on: Margolis et al. lack of Effectiveness of hyperbaric oxygen therapy
      for the treatment of diabetic foot ulcer and the prevention of amputation: a
      cohort study. Diabetes Care 2013;36:1961-1966.

PMID- 23881985
TI  - Response to Comments on: Margolis et al. Lack of effectiveness of hyperbaric
      oxygen therapy for the treatment of diabetic foot ulcer and the prevention of
      amputation: a cohort study. Diabetes Care 2013;36:1961-1966.

PMID- 23881986
TI  - Response to Comment on: Hanssen et al. Associations between the ankle-brachial
      index and cardiovascular and all-cause mortality are similar in individuals
      without and with type 2 diabetes: nineteen-year follow-up of a population-based
      cohort study. Diabetes Care 2012;35:1731-1735.

PMID- 23881988
TI  - Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled
      analysis from seven randomized controlled trials.
AB  - PURPOSE: his analysis pooled individual patient data from randomized controlled
      trials (RCTs) to more thoroughly examine clinical outcomes when adding
      bevacizumab to chemotherapy for patients with metastatic colorectal cancer
      (mCRC). PATIENTS AND METHODS: Patient data were pooled from the first-line
      AVF2107, NO16966, ARTIST, AVF0780, AVF2192, and AGITG MAX RCTs and the second
      line E3200 RCT. All analyses were based on the intent-to-treat population. To
      assess differences in time-to-event variables by treatment (chemotherapy with or
      without placebo vs. chemotherapy plus bevacizumab), stratified random-effects
      (overall) and fixed-effects (subgroup comparisons) models were used to estimate
      pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The
      analysis population comprised 3,763 patients (1,773 chemotherapy with or without
      placebo; 1,990 chemotherapy plus bevacizumab). The addition of bevacizumab to
      chemotherapy was associated with statistically significant increases in overall
      survival (OS; HR, 0.80; 95% CI, 0.71-0.90) and progression-free survival (PFS;
      HR, 0.57; 95% CI, 0.46-0.71). The effects on OS and PFS across subgroups defined
      by chemotherapy backbone (oxaliplatin-based, irinotecan-based), extent of disease
      (liver metastases only, extensive disease), age (<65, >=65 years), Eastern
      Cooperative Oncology Group performance status (0, >=1), and KRAS status (wild
      type, mutant) were consistent with the overall analysis. Incidence rates of grade
      >=3 hypertension, proteinuria, bleeding, wound-healing complications,
      gastrointestinal perforations, and thromboembolic events were increased with
      bevacizumab treatment. CONCLUSION: The use of bevacizumab with chemotherapy
      resulted in statistically significant increases in OS and PFS for patients with
      mCRC. The PFS benefit extended across the clinically relevant subgroups examined.
      The observed safety profile of bevacizumab was consistent with that reported in
      individual trials.

PMID- 23881987
TI  - Thyroid lymphoma: recent advances in diagnosis and optimal management strategies.
AB  - Primary thyroid lymphoma is rare, composing approximately 5% of all thyroid
      malignancies and less than 3% of all extranodal lymphomas. It typically presents
      as a rapidly enlarging goiter with associated compressive symptoms. Thyroid
      ultrasound and fine needle aspiration cytology, using flow cytometry and
      immunohistochemistry, remain the main modalities used to confirm the presence of
      lymphoma. The increasing use of an ultrasound-guided core biopsy to achieve an
      accurate diagnosis has further limited the role of surgery. An open surgical
      biopsy may still be required not only for definitive diagnosis but also to
      confirm the subtype of lymphoma. There are limited numbers of randomized or
      prospective trials to guide management, and controversy remains over optimal
      treatment. Treatment and prognosis of this disease can be dichotomized into two
      separate groups: pure mucosa-associated lymphoid tissue (MALT) lymphoma and
      diffuse large B-cell lymphoma (DLBCL) or mixed subtypes. Early stage (stage IE)
      intrathyroidal MALT lymphomas typically have an indolent course and may be
      treated with single-modality surgery, radiotherapy, or a combination of both.
      DLBCLs are more aggressive, and survival outcomes are highest with multimodal
      therapy incorporating monoclonal antibodies, chemotherapy, and radiotherapy. The
      prognosis is generally excellent but can be varied because of the heterogeneous
      nature of thyroid lymphomas. The aim of this paper is to discuss the changes in
      diagnostic modalities and to focus on the recent alterations in the management of
      this rare disease, including targeted therapies as well as the more limited role
      of the endocrine surgeon. 

PMID- 23881989
TI  - Differential chemotherapeutic sensitivity for breast tumors with "BRCAness": a
      review.
AB  - BRCA1 or BRCA2 mutations predispose to cancer development, primarily through
      their loss of role in the repair of DNA double-strand breaks. They play a key
      role in homologous recombination repair, which is a conservative, error-free DNA
      repair mechanism. When mutated, other alternative, error-prone mechanisms for DNA
      repair take over, leading to genomic instability. Somatic mutations are rare in
      sporadic breast tumors, but expression of BRCA1 and BRCA2 genes can be
      downregulated in other mechanistic ways. These tumors have similar features in
      terms of their phenotypic and genotypic profiles, which are normally regulated by
      these genes, and mutations lead to defective DNA repair capacity, called
      "BRCAness." Attempts have been made to exploit this differentially expressed
      feature between tumors and normal tissues by treatment with DNA-damaging
      chemotherapy agents. Cells with this functional BRCA deficiency should be
      selectively susceptible to DNA-damaging drugs. Preclinical and early clinical
      (primarily retrospective) evidence supports this approach. In contrast, there is
      emerging evidence of relative resistance of tumors containing BRCA1 or BRCA2
      mutations (or BRCAness) to taxanes. In this review, we summarize the data
      supporting differential chemotherapeutic sensitivity on the basis of defective
      DNA repair. If confirmed with available, clinically applicable techniques, this
      differential chemosensitivity could lead to treatment choices in breast cancer
      that have a more individualized biologic basis. 

PMID- 23881991
TI  - Doubts about the BMA's policy on bicycle helmets.

PMID- 23881990
TI  - The role of pegylated liposomal doxorubicin in ovarian cancer: a meta-analysis of
      randomized clinical trials.
AB  - BACKGROUND: Recent studies suggest that carboplatin with pegylated liposomal
      doxorubicin (C+PLD) is as efficacious as carboplatin with paclitaxel (C+P) and
      possibly is more tolerable for ovarian cancer therapy. Pegylated liposomal
      doxorubicin (PLD) may also be efficacious and tolerable as monotherapy in
      recurrent or platinum-resistant disease. We performed a meta-analysis of
      randomized trials in order to elucidate the role of PLD in ovarian cancer.
      METHODS: We searched PubMed, Scopus, and ISI Web of Knowledge for studies
      comparing C+PLD with C+P and comparing PLD with another monotherapy. Summary
      hazard ratios (HRs) and relative risks with their corresponding 95% confidence
      intervals (CIs) were calculated using a fixed-effects model. RESULTS: Three
      trials were included in the doublet regimen analysis, and five trials were
      included in the monotherapy regimen analysis. C+PLD provided superior progression
      free survival (PFS) (HR, 0.87; 95% CI, 0.78-0.96) and similar overall survival
      (OS; HR, 0.95; 95% CI, 0.84-1.07) compared with C+P. There was no evidence of
      improved tolerability: C+PLD had more gastrointestinal toxicity, anemia,
      thrombocytopenia, cutaneous toxicity, and mucositis/stomatitis, although there
      was less neutropenia, neuropathy, and alopecia. PLD monotherapy had similar PFS
      (HR, 0.99; 95% CI, 0.89-1.11) and OS (HR, 0.99; 95% CI, 0.88-1.11) to other
      monotherapies, but it was more tolerable. There was less neutropenia, anemia,
      thrombocytopenia, and gastrointestinal toxicity, although cutaneous toxicity was
      increased. CONCLUSION: C+PLD had better PFS and similar OS compared with C+P and
      had a very different toxicity profile. Therapy selection could be based on
      patient risks for side effects. PLD is as efficacious as other monotherapies and
      is more tolerable.

PMID- 23881992
TI  - Time to stop using minocycline?

PMID- 23881993
TI  - The US Office for Human Research Protections' judgment of the SUPPORT trial seems
      entirely reasonable.

PMID- 23881994
TI  - The US Office for Human Research Protections' intervention in the SUPPORT trial
      was indeed ill conceived.

PMID- 23881995
TI  - It's time to ban obesity in NHS employees.

PMID- 23881996
TI  - Patients with cancer say yes to palliative chemotherapy.

PMID- 23881997
TI  - Best palliation in advanced cancer is often achieved by treating the cancer.

PMID- 23881998
TI  - Neuropsychiatric adverse effects of oseltamivir in the FDA Adverse Event
      Reporting System, 1999-2012.

PMID- 23881999
TI  - Study stokes debate over patterns of non-communicable disease in India.

PMID- 23882000
TI  - Trade talks won't affect health policy, say EU officials.

PMID- 23882001
TI  - Drug trade bodies rally patient groups to deflect calls for full trial data.

PMID- 23882002
TI  - Influences of fundamental frequency, formant frequencies, aperiodicity, and
      spectrum level on the perception of voice gender.
AB  - PURPOSE: To determine the relative importance of acoustic parameters (fundamental
      frequency [F0], formant frequencies [FFs], aperiodicity, and spectrum level [SL])
      on voice gender perception, the authors used a novel parameter-morphing approach
      that, unlike spectral envelope shifting, allows the application of nonuniform
      scale factors to transform formants and more direct comparison of parameter
      impact. METHOD: In each of 2 experiments, 16 listeners with normal hearing (8
      female, 8 male) classified voice gender for morphs between female and male
      speakers, using syllable tokens from 2 male-female speaker pairs. Morphs varied
      single acoustic parameters (Experiment 1) or selected combinations (Experiment
      2), keeping residual parameters androgynous, as determined in a baseline
      experiment. RESULTS: The strongest cue related to gender perception was F0,
      followed by FF and SL. Aperiodicity did not systematically influence gender
      perception. Morphing F0 and FF in conjunction produced convincing changes in
      perceived gender-changes that were equivalent to those for Full morphs
      interpolating all parameters. Despite the importance of F0, morphing FF and SL in
      combination produced effective changes in voice gender perception. CONCLUSIONS:
      The most important single parameters for gender perception are, in order, F0, FF,
      and SL. At the same time, F0 and vocal tract resonances have a comparable impact
      on voice gender perception.

PMID- 23882003
TI  - Idiom, syntax, and advanced theory of mind abilities in children with autism
      spectrum disorders.
AB  - PURPOSE: When researchers investigate figurative language abilities (including
      idioms) in children with autism spectrum disorder (ASD), syntax abilities may be
      more important than once considered. In addition, there are limitations to the
      overreliance on false-belief tasks to measure theory of mind (TOM) abilities. In
      the current study, the authors investigated idiom, syntax, and advanced TOM
      abilities in children with ASD compared to children with typical development
      (TD). METHOD: Twenty-six children with ASD, ages 5 to 12 years, were compared to
      individuals in each of 2 control groups of children with TD: 1 matched on
      chronological age and nonverbal IQ, and 1 matched on syntax age-equivalence and
      raw scores. Idiom comprehension, syntax, vocabulary, and 2 measures of advanced
      TOM abilities were examined. RESULTS: Although children with ASD performed worse
      on idiom comprehension compared to the age-matched group with TD, they exhibited
      comparable idiom performance to the syntax-matched group with TD. Advanced TOM
      abilities were related to idiom comprehension for children with ASD, but not for
      children with TD, above the contributions of basic language abilities.
      CONCLUSION: Syntax abilities should be used as a matching variable when examining
      figurative or other late-developing language skills.

PMID- 23882004
TI  - Grammatical outcomes of 3- and 6-year-old children who are hard of hearing.
AB  - PURPOSE: Spoken language skills of 3- and 6-year-old children who are hard of
      hearing (HH) were compared with those of children with normal hearing (NH).
      METHOD: Language skills were measured via mean length of utterance in words
      (MLUw) and percent correct use of finite verb morphology in obligatory contexts
      based on spontaneous conversational samples gathered from 185 children (145 HH,
      40 NH). Aided speech intelligibility index (SII), better-ear pure-tone average
      (BE-PTA), maternal education, and age of amplification were used to predict
      outcomes within the HH group. RESULTS: On average, the HH group had MLUws that
      were 0.25-0.5 words shorter than the NH group at both ages, and they produced
      fewer obligatory verb morphemes. After age, aided SII and age of amplification
      predicted MLUw. Aided SII and BE-PTA were not interchangeable in this analysis.
      Age followed by either BE-PTA or aided SII best predicted verb morphology use.
      CONCLUSIONS: Children who are HH lag behind their peers with NH in grammatical
      aspects of language. Although some children appear to catch up, more than half of
      the children who are HH fell below the 25th percentile. Continued monitoring of
      language outcomes is warranted considering that children who are HH are at
      increased risk for language learning difficulties.

PMID- 23882006
TI  - The effects of semantic context and the type and amount of acoustic distortion on
      lexical decision by younger and older adults.
AB  - PURPOSE: In this study, the authors investigated how acoustic distortion affected
      younger and older adults' use of context in a lexical decision task. METHOD: The
      authors measured lexical decision reaction times (RTs) when intact target words
      followed acoustically distorted sentence contexts. Contexts were semantically
      congruent, neutral, or incongruent. Younger adults (n = 216) were tested on three
      distortion types: low-pass filtering, time compression, and masking by
      multitalker babble, using two amounts of distortion selected to control for word
      recognition accuracy. Older adults (n = 108) were tested on two amounts of time
      compression and one low-pass filtering condition. RESULTS: For both age groups,
      there was robust facilitation by congruent contexts but minimal inhibition by
      incongruent contexts. Facilitation decreased as distortion increased. Older
      listeners had slower RTs than younger listeners, but this difference was smaller
      in congruent than in neutral or incongruent conditions. After controlling for
      word recognition accuracy, older listeners' RTs were slower in time-compressed
      than in low-pass filtering conditions, but younger listeners performed similarly
      in both conditions. CONCLUSIONS: These RT results highlight the interdependence
      between bottom-up sensory and top-down semantic processing. Consistent with
      previous findings based on accuracy measures, compared with younger adults, older
      adults were disproportionately slowed when speech was time compressed but more
      facilitated by congruent contexts.

PMID- 23882005
TI  - The effect of incremental changes in phonotactic probability and neighborhood
      density on word learning by preschool children.
AB  - PURPOSE: Phonotactic probability or neighborhood density has predominately been
      defined through the use of gross distinctions (i.e., low vs. high). In the
      current studies, the authors examined the influence of finer changes in
      probability (Experiment 1) and density (Experiment 2) on word learning. METHOD:
      The authors examined the full range of probability or density by sampling 5
      nonwords from each of 4 quartiles. Three- and 5-year-old children received
      training on nonword-nonobject pairs. Learning was measured in a picture-naming
      task immediately following training and 1 week after training. Results were
      analyzed through the use of multilevel modeling. RESULTS: A linear spline model
      best captured nonlinearities in phonotactic probability. Specifically, word
      learning improved as probability increased in the lowest quartile, worsened as
      probability increased in the mid-low quartile, and then remained stable and poor
      in the 2 highest quartiles. An ordinary linear model sufficiently described
      neighborhood density. Here, word learning improved as density increased across
      all quartiles. CONCLUSION: Given these different patterns, phonotactic
      probability and neighborhood density appear to influence different word learning
      processes. Specifically, phonotactic probability may affect recognition that a
      sound sequence is an acceptable word in the language and is a novel word for the
      child, whereas neighborhood density may influence creation of a new
      representation in long-term memory.

PMID- 23882007
TI  - The influence of semantic context on the perception of Spanish-accented American
      English.
AB  - PURPOSE: In this article, the authors examine (a) the effect of semantic context
      on accentedness, comprehensibility, and intelligibility of Spanish-accented
      American English (AE) as judged by monolingual AE listeners and (b) the
      interaction of semantic context and accentedness on comprehensibility and
      intelligibility. METHOD: Twenty adult native (L1) Spanish speakers proficient in
      AE and 4 L1 AE speakers (controls) read 48 statements consisting of true-false,
      semantically meaningful, and semantically anomalous sentences. Eighty monolingual
      AE listeners assessed accentedness, comprehensibility, and intelligibility of the
      statements. RESULTS: A significant main effect was found for semantic category on
      all 3 dependent variables. Accents were perceived to be stronger, and both
      comprehensibility and intelligibility were worse, in semantically anomalous
      contexts. Speaker data were grouped into strong, mid-level, and mild accents. The
      interaction between semantic category and accent was significant for both
      comprehensibility and intelligibility. The effect of semantic context was
      strongest for strong accents. Intelligibility was excellent for speakers with mid
      level accents in true-false and semantically meaningful contexts, and it was
      excellent for mild accents in all contexts. CONCLUSIONS: Listeners access
      semantic information, in addition to phonetic and phonotactic features, in the
      perception of nonnative speech. Both accent level and semantic context are
      important in research on foreign-accented speech.

PMID- 23882008
TI  - Identification of specific language impairment in bilingual children: I.
      Assessment in English.
AB  - PURPOSE: This study was designed to derive cut scores for English testing for use
      in identifying specific language impairment (SLI) in bilingual children who were
      learning English as a second language. METHOD: In a 1-gate design, 167 children
      received comprehensive language assessments in English and Spanish during their
      first-grade year. The reference standard was identification by a team of expert
      bilingual speech-language pathologists. Receiver operating curve (ROC) analyses
      were used to identify the optimal prediction model for SLI. RESULTS: The
      original, English EpiSLI criteria (Tomblin, Records, & Zhang, 1996) yielded a
      sensitivity of .95 and a specificity of .45 (LR+ = 1.73, LR- = 0.11, and AUC =
      .79) for our bilinguals. Revised cutoff scores yielded a sensitivity of .86 and a
      specificity of .68 (LR+ = 2.67, LR- = 0.21, and AUC = .77). An optimal prediction
      model yielded a sensitivity of .81 and a specificity of .81 (LR+ = 4.37, LR- =
      0.23 and AUC = .85). CONCLUSION: The results of English testing could be used to
      make a reasonably accurate diagnostic decision for bilingual children who had
      attended public school for at least 1 year and were using English at least 30% of
      the time.

PMID- 23882009
TI  - Rate and phonological variation in preschool children: effects of modeling and
      directed influence.
AB  - PURPOSE: To explore the effect of modeling and explicit elicitation of slow and
      accurately produced speech in typically developing preschool children. Optional
      phonological reductions (e.g., deleted final stops) and changes in speech rate
      were examined in response to an adult conversational speaker's speech style.
      METHOD: Forty 3- and 4-year-olds (20 each) were tested in 3 tasks: (a) immediate
      repetition of a model, (b) spontaneous speech, and (c) directed speech style
      (cueing to correct "sloppy" speech). In Task 1, half of each group heard fast and
      hypoarticulated versus slow and hyperarticulated speech for a between-group
      response-to-model comparison. Tasks 2 and 3 were compared within subjects.
      RESULTS: Task 1 demonstrated that both age groups aligned with the speaker's rate
      and phonological variants usage when repeating a model. Tasks 2 and 3 revealed
      that 4-year-olds varied phonological reduction patterns according to the task
      demands, whereas 3-year-olds maintained consistent patterns of usage. In
      addition, neither group successfully realigned with the rapid speech rate in Task
      3. CONCLUSIONS: These results contribute to an evidence base supporting the
      practice of modeling slow and clear speech to children with various production
      disorders. Further research is needed to explore the cognitive-linguistic
      processes underlying alignment before findings are applied to clinical
      populations.

PMID- 23882010
TI  - Who to screen for lung cancer.

PMID- 23882011
TI  - EsiB, a novel pathogenic Escherichia coli secretory immunoglobulin A-binding
      protein impairing neutrophil activation.
AB  - In this study, we have characterized the functional properties of a novel
      Escherichia coli antigen named EsiB (E. coli secretory immunoglobulin A-binding
      protein), recently reported to protect mice from sepsis. Gene distribution
      analysis of a panel of 267 strains representative of different E. coli pathotypes
      revealed that esiB is preferentially associated with extraintestinal strains,
      while the gene is rarely found in either intestinal or nonpathogenic strains.
      These findings were supported by the presence of anti-EsiB antibodies in the sera
      of patients affected by urinary tract infections (UTIs). By solving its crystal
      structure, we observed that EsiB adopts a superhelical fold composed of Sel1-like
      repeats (SLRs), a feature often associated with bacterial proteins possessing
      immunomodulatory functions. Indeed, we found that EsiB interacts with secretory
      immunoglobulin A (SIgA) through a specific motif identified by an immunocapturing
      approach. Functional assays showed that EsiB binding to SIgA is likely to
      interfere with productive FcalphaRI signaling, by inhibiting both SIgA-induced
      neutrophil chemotaxis and respiratory burst. Indeed, EsiB hampers SIgA-mediated
      signaling events by reducing the phosphorylation status of key signal-transducer
      cytosolic proteins, including mitogen-activated kinases. We propose that the
      interference with such immune events could contribute to the capacity of the
      bacterium to avoid clearance by neutrophils, as well as reducing the recruitment
      of immune cells to the infection site. IMPORTANCE: Pathogenic Escherichia coli
      infections have recently been exacerbated by increasing antibiotic resistance and
      the number of recurrent contagions. Attempts to develop preventive strategies
      against E. coli have not been successful, mainly due to the large antigenic and
      genetic variability of virulence factors, but also due to the complexity of the
      mechanisms used by the pathogen to evade the immune system. In this work, we
      elucidated the function of a recently discovered protective antigen, named EsiB,
      and described its capacity to interact with secretory immunoglobulin A (SIgA) and
      impair effector functions. This work unravels a novel strategy used by E. coli to
      subvert the host immune response and avoid neutrophil-dependent clearance.

PMID- 23882012
TI  - Clinically relevant mutant DNA gyrase alters supercoiling, changes the
      transcriptome, and confers multidrug resistance.
AB  - Bacterial DNA is maintained in a supercoiled state controlled by the action of
      topoisomerases. Alterations in supercoiling affect fundamental cellular
      processes, including transcription. Here, we show that substitution at position
      87 of GyrA of Salmonella influences sensitivity to antibiotics, including
      nonquinolone drugs, alters global supercoiling, and results in an altered
      transcriptome with increased expression of stress response pathways. Decreased
      susceptibility to multiple antibiotics seen with a GyrA Asp87Gly mutant was not a
      result of increased efflux activity or reduced reactive-oxygen production. These
      data show that a frequently observed and clinically relevant substitution within
      GyrA results in altered expression of numerous genes, including those important
      in bacterial survival of stress, suggesting that GyrA mutants may have a
      selective advantage under specific conditions. Our findings help contextualize
      the high rate of quinolone resistance in pathogenic strains of bacteria and may
      partly explain why such mutant strains are evolutionarily successful. IMPORTANCE:
      Fluoroquinolones are a powerful group of antibiotics that target bacterial
      enzymes involved in helping bacteria maintain the conformation of their
      chromosome. Mutations in the target enzymes allow bacteria to become resistant to
      these antibiotics, and fluoroquinolone resistance is common. We show here that
      these mutations also provide protection against a broad range of other
      antimicrobials by triggering a defensive stress response in the cell. This work
      suggests that fluoroquinolone resistance mutations may be beneficial under a
      range of conditions.

PMID- 23882013
TI  - Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from
      the division septum and remodels cell membrane phospholipids.
AB  - Treatment of multidrug-resistant enterococci has become a challenging clinical
      problem in hospitals around the world due to the lack of reliable therapeutic
      options. Daptomycin (DAP), a cell membrane-targeting cationic antimicrobial
      lipopeptide, is the only antibiotic with in vitro bactericidal activity against
      vancomycin-resistant enterococci (VRE). However, the clinical use of DAP against
      VRE is threatened by emergence of resistance during therapy, but the mechanisms
      leading to DAP resistance are not fully understood. The mechanism of action of
      DAP involves interactions with the cell membrane in a calcium-dependent manner,
      mainly at the level of the bacterial septum. Previously, we demonstrated that
      development of DAP resistance in vancomycin-resistant Enterococcus faecalis is
      associated with mutations in genes encoding proteins with two main functions, (i)
      control of the cell envelope stress response to antibiotics and antimicrobial
      peptides (LiaFSR system) and (ii) cell membrane phospholipid metabolism
      (glycerophosphoryl diester phosphodiesterase and cardiolipin synthase). In this
      work, we show that these VRE can resist DAP-elicited cell membrane damage by
      diverting the antibiotic away from its principal target (division septum) to
      other distinct cell membrane regions. DAP septal diversion by DAP-resistant E.
      faecalis is mediated by initial redistribution of cell membrane cardiolipin-rich
      microdomains associated with a single amino acid deletion within the
      transmembrane protein LiaF (a member of a three-component regulatory system
      [LiaFSR] involved in cell envelope homeostasis). Full expression of DAP
      resistance requires additional mutations in enzymes (glycerophosphoryl diester
      phosphodiesterase and cardiolipin synthase) that alter cell membrane phospholipid
      content. Our findings describe a novel mechanism of bacterial resistance to
      cationic antimicrobial peptides. IMPORTANCE: The emergence of antibiotic
      resistance in bacterial pathogens is a threat to public health. Understanding the
      mechanisms of resistance is of crucial importance to develop new strategies to
      combat multidrug-resistant microorganisms. Vancomycin-resistant enterococci (VRE)
      are one of the most recalcitrant hospital-associated pathogens against which new
      therapies are urgently needed. Daptomycin (DAP) is a calcium-decorated
      antimicrobial lipopeptide whose target is the bacterial cell membrane. A current
      paradigm suggests that Gram-positive bacteria become resistant to cationic
      antimicrobial peptides via an electrostatic repulsion of the antibiotic molecule
      from a more positively charged cell surface. In this work, we provide evidence
      that VRE use a novel strategy to avoid DAP-elicited killing. Instead of
      "repelling" the antibiotic from the cell surface, VRE diverts the antibiotic
      molecule from the septum and "traps" it in distinct membrane regions. We provide
      genetic and biochemical bases responsible for the mechanism of resistance and
      disclose new targets for potential antimicrobial development.

PMID- 23882014
TI  - Two independent pathways for self-recognition in Proteus mirabilis are linked by
      type VI-dependent export.
AB  - Swarming colonies of the bacterium Proteus mirabilis are capable of self
      recognition and territorial behavior. Swarms of independent P. mirabilis isolates
      can recognize each other as foreign and establish a visible boundary where they
      meet; in contrast, genetically identical swarms merge. The ids genes, which
      encode self-identity proteins, are necessary but not sufficient for this
      territorial behavior. Here we have identified two new gene clusters: one (idr)
      encodes rhs-related products, and another (tss) encodes a putative type VI
      secretion (T6S) apparatus. The Ids and Idr proteins function independently of
      each other in extracellular transport and in territorial behaviors; however,
      these self-recognition systems are linked via this type VI secretion system. The
      T6S system is required for export of select Ids and Idr proteins. Our results
      provide a mechanistic and physiological basis for the fundamental behaviors of
      self-recognition and territoriality in a bacterial model system. IMPORTANCE: Our
      results support a model in which self-recognition in P. mirabilis is achieved by
      the combined action of two independent pathways linked by a shared machinery for
      export of encoded self-recognition elements. These proteins together form a
      mechanistic network for self-recognition that can serve as a foundation for
      examining the prevalent biological phenomena of territorial behaviors and self
      recognition in a simple, bacterial model system.

PMID- 23882015
TI  - Interspecies communication among commensal and pathogenic streptococci.
AB  - Quorum sensing (QS) regulates diverse and coordinated behaviors in bacteria,
      including the production of virulence factors, biofilm formation, sporulation,
      and competence development. It is now established that some streptococci utilize
      Rgg-type proteins in concert with short hydrophobic peptides (SHPs) to mediate
      QS, and sequence analysis reveals that several streptococcal species contain
      highly homologous Rgg/SHP pairs. In group A streptococcus (GAS), two SHPs (SHP2
      and SHP3 [SHP2/3]) were previously identified to be important in GAS biofilm
      formation. SHP2/3 are detected by two antagonistic regulators, Rgg2 and Rgg3,
      which control expression of the shp genes. In group B streptococcus (GBS), RovS
      is a known virulence gene regulator and ortholog of Rgg2, whereas no apparent
      Rgg3 homolog exists. Adjacent to rovS is a gene (shp1520) encoding a peptide
      nearly identical to SHP2. Using isogenic mutant strains and transcriptional
      reporters, we confirmed that RovS/SHP1520 comprise a QS circuit in GBS. More
      important, we performed experiments demonstrating that production and secretion
      of SHP1520 by GBS can modulate Rgg2/3-regulated gene expression in GAS in trans;
      likewise, SHP2/3 production by GAS can stimulate RovS-mediated gene regulation in
      GBS. An isolate of Streptococcus dysgalactiae subsp. equisimilis also produced a
      secreted factor capable of simulating the QS circuits of both GAS and GBS, and
      sequencing confirms the presence of an orthologous Rgg2/SHP2 pair in this species
      as well. To our knowledge, this is the first documented case of bidirectional
      signaling between streptococcal species in coculture and suggests a role for
      orthologous Rgg/SHP systems in interspecies communication between important human
      pathogens. IMPORTANCE: Pathogenic streptococci, such as group A (GAS) and group B
      (GBS) streptococcus, are able to persist in the human body without causing
      disease but become pathogenic under certain conditions that are not fully
      characterized. Environmental cues and interspecies signaling between members of
      the human flora likely play an important role in the transition to a disease
      state. Since quorum-sensing (QS) peptides have been consistently shown to
      regulate virulence factor production in pathogenic species, the ability of
      bacteria to signal via these peptides may prove to be an important link between
      the carrier and pathogenic states. Here we provide evidence of a bidirectional QS
      system between GAS, GBS, and Streptococcus dysgalactiae subsp. equisimilis,
      demonstrating the possibility of evolved communication systems between human
      pathogens.

PMID- 23882016
TI  - Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and
      transition from asymptomatic colonization to disease.
AB  - Streptococcus pneumoniae is a common human nasopharyngeal commensal colonizing
      10% to 40% of healthy individuals, depending on age. Despite a low invasive
      disease rate, widespread carriage ensures that infection occurs often enough to
      make S. pneumoniae a leading bacterial cause of respiratory disease worldwide.
      However, the mechanisms behind transition from asymptomatic colonization to
      dissemination and disease in otherwise sterile sites remain poorly understood but
      are epidemiologically strongly linked to infection with respiratory viruses. In
      this report, we show that infection with influenza A virus and treatment with the
      resulting host signals (febrile-range temperatures, norepinephrine,
      extracytoplasmic ATP, and increased nutrient availability) induce the release of
      bacteria from biofilms in a newly developed biofilm model on live epithelial
      cells both in vitro and during in vivo colonization. These dispersed bacteria
      have distinct phenotypic properties different from those of both biofilm and
      broth-grown, planktonic bacteria, with the dispersed population showing
      differential virulence gene expression characteristics resulting in a
      significantly increased ability to disseminate and cause infection of otherwise
      sterile sites, such as the middle ear, lungs, and bloodstream. The results offer
      novel and important insights into the role of interkingdom signaling between
      microbe and host during biofilm dispersion and transition to acute disease.
      IMPORTANCE: This report addresses the mechanisms involved in transition from
      pneumococcal asymptomatic colonization to disease. In this study, we determined
      that changes in the nasopharyngeal environment result in the release of bacteria
      from colonizing biofilms with a gene expression and virulence phenotype different
      not only from that of colonizing biofilm bacteria but also from that of the broth
      grown planktonic bacteria commonly used for pathogenesis studies. The work
      importantly also identifies specific host factors responsible for the release of
      bacteria and their changed phenotype. We show that these interkingdom signals are
      recognized by bacteria and are induced by influenza virus infection, which is
      epidemiologically strongly associated with transition to secondary pneumococcal
      disease. As virus infection is a common inducer of transition to disease among
      species occupying the nasopharynx, the results of this study may provide a basis
      for better understanding of the signals involved in the transition from
      colonization to disease in the human nasopharynx.

PMID- 23882017
TI  - Receptor polymorphism restricts contact-dependent growth inhibition to members of
      the same species.
AB  - Bacteria that express contact-dependent growth inhibition (CDI) systems
      outcompete siblings that lack immunity, suggesting that CDI mediates
      intercellular competition. To further explore the role of CDI in competition, we
      determined the target cell range of the CDIEC93 system from Escherichia coli
      EC93. The CdiAEC93 effector protein recognizes the widely conserved BamA protein
      as a receptor, yet E. coli EC93 does not inhibit other enterobacterial species.
      The predicted membrane topology of BamA indicates that three of its extracellular
      loops vary considerably between species, suggesting that loop heterogeneity may
      control CDI specificity. Consistent with this hypothesis, other enterobacteria
      are sensitized to CDIEC93 upon the expression of E. coli bamA and E. coli cells
      become CDIEC93 resistant when bamA is replaced with alleles from other species.
      Our data indicate that BamA loops 6 and 7 form the CdiAEC93-binding epitope and
      their variation between species restricts CDIEC93 target cell selection. Although
      BamA loops 6 and 7 vary dramatically between species, these regions are identical
      in hundreds of E. coli strains, suggesting that BamAEcoli and CdiAEC93 play a
      role in self-nonself discrimination. IMPORTANCE: Contact-dependent growth
      inhibition (CDI) systems are widespread among Gram-negative bacteria, enabling
      them to bind to neighboring bacterial cells and deliver protein toxins that
      inhibit cell growth. In this study, we tested the role of CDI in interspecies
      competition using intestinal isolate Escherichia coli EC93 as an inhibitor cell
      model. Although E. coli EC93 inhibits different E. coli strains, other bacterial
      species from the intestine are completely resistant to CDI. We show that
      resistance is due to small variations in the CDI receptor that prevent other
      species from being recognized as target cells. CDI receptor interactions thus
      provide a mechanism by which bacteria can distinguish siblings and other close
      relatives (self) from more distant relatives or other species of bacteria
      (nonself). Our results provide a possible means by which antimicrobials could be
      directed to one or only a few related bacterial pathogens by using a specific
      receptor "zip code."

PMID- 23882019
TI  - Clinical trial results: Sharing results, speeding discoveries.

PMID- 23882018
TI  - Cancer in Botswana: the second wave of AIDS in Sub-Saharan Africa.

PMID- 23882020
TI  - Cancer in the shadow of the AIDS epidemic in southern Africa.

PMID- 23882022
TI  - Systemic tryptophan and kynurenine catabolite levels relate to severity of
      rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group
      design.
AB  - BACKGROUND: Patients with allergic asthma have exacerbations which are frequently
      caused by rhinovirus infection. The antiviral tryptophan-catabolising enzyme
      indoleamine 2,3-dioxygenase (IDO) is induced by interferon-gamma and suppressed
      by Th2 mediators interleukin (IL)-4 and IL-13. We hypothesised that local IDO
      activity after viral airway infection is lower in patients with allergic asthma
      than in healthy controls. OBJECTIVE: To determine whether IDO activity differs
      between patients with allergic asthma and healthy individuals before and after
      rhinovirus infection. METHODS: Healthy individuals and patients with allergic
      asthma were experimentally infected with low-dose (10 TCID50) rhinovirus 16.
      Blood, bronchoalveolar lavage fluid and exhaled breath condensate (for mass
      spectrometry by UPLC-MS/MS) were obtained before and after rhinovirus challenge.
      RESULTS: IDO activity was not induced by rhinovirus infection in either group,
      despite increases in cold scores. However, baseline pulmonary IDO activity was
      lower in patients with allergic asthma than in healthy individuals. In contrast,
      systemic tryptophan and its catabolites were markedly higher in patients with
      allergic asthma. Moreover, systemic quinolinic acid and tryptophan were
      associated with eosinophil cationic protein (r=0.43 and r=0.78, respectively) and
      eosinophils (r=0.38 and r=0.58, respectively) in bronchoalveolar lavage fluid and
      peak asthma symptom scores after rhinovirus challenge (r=0.53 and r=0.64,
      respectively). CONCLUSIONS: Rhinovirus infection by itself induces no IDO
      activity, but the reduced pulmonary IDO activity in patients with allergic asthma
      at baseline may underlie a reduced control of viral infections. Notably, the
      enhanced systemic catabolism of tryptophan in patients with allergic asthma was
      strongly related to the outcome of rhinovirus challenge in asthma and may serve
      as a prognostic factor.

PMID- 23882023
TI  - Network-based analysis of genome wide association data provides novel candidate
      genes for lipid and lipoprotein traits.
AB  - Genome wide association studies (GWAS) identify susceptibility loci for complex
      traits, but do not identify particular genes of interest. Integration of
      functional and network information may help in overcoming this limitation and
      identifying new susceptibility loci. Using GWAS and comorbidity data, we present
      a network-based approach to predict candidate genes for lipid and lipoprotein
      traits. We apply a prediction pipeline incorporating interactome, co-expression,
      and comorbidity data to Global Lipids Genetics Consortium (GLGC) GWAS for four
      traits of interest, identifying phenotypically coherent modules. These modules
      provide insights regarding gene involvement in complex phenotypes with multiple
      susceptibility alleles and low effect sizes. To experimentally test our
      predictions, we selected four candidate genes and genotyped representative SNPs
      in the Malmo Diet and Cancer Cardiovascular Cohort. We found significant
      associations with LDL-C and total-cholesterol levels for a synonymous SNP
      (rs234706) in the cystathionine beta-synthase (CBS) gene (p = 1 * 10(-5) and
      adjusted-p = 0.013, respectively). Further, liver samples taken from 206 patients
      revealed that patients with the minor allele of rs234706 had significant
      dysregulation of CBS (p = 0.04). Despite the known biological role of CBS in
      lipid metabolism, SNPs within the locus have not yet been identified in GWAS of
      lipoprotein traits. Thus, the GWAS-based Comorbidity Module (GCM) approach
      identifies candidate genes missed by GWAS studies, serving as a broadly
      applicable tool for the investigation of other complex disease phenotypes. 

PMID- 23882024
TI  - Molecular responses of mouse macrophages to copper and copper oxide nanoparticles
      inferred from proteomic analyses.
AB  - The molecular responses of macrophages to copper-based nanoparticles have been
      investigated via a combination of proteomic and biochemical approaches, using the
      RAW264.7 cell line as a model. Both metallic copper and copper oxide
      nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles
      used as controls. Proteomic analysis highlighted changes in proteins implicated
      in oxidative stress responses (superoxide dismutases and peroxiredoxins),
      glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins
      (especially oxidative phosphorylation complex subunits). Validation studies
      employing functional analyses showed that the increases in glutathione
      biosynthesis and in mitochondrial complexes observed in the proteomic screen were
      critical to cell survival upon stress with copper-based nanoparticles;
      pharmacological inhibition of these two pathways enhanced cell vulnerability to
      copper-based nanoparticles, but not to copper ions. Furthermore, functional
      analyses using primary macrophages derived from bone marrow showed a decrease in
      reduced glutathione levels, a decrease in the mitochondrial transmembrane
      potential, and inhibition of phagocytosis and of lipopolysaccharide-induced
      nitric oxide production. However, only a fraction of these effects could be
      obtained with copper ions. In conclusion, this study showed that macrophage
      functions are significantly altered by copper-based nanoparticles. Also
      highlighted are the cellular pathways modulated by cells for survival and the
      exemplified cross-toxicities that can occur between copper-based nanoparticles
      and pharmacological agents. 

PMID- 23882025
TI  - Multi-dimensional co-separation analysis reveals protein-protein interactions
      defining plasma lipoprotein subspecies.
AB  - The distribution of circulating lipoprotein particles affects the risk for
      cardiovascular disease (CVD) in humans. Lipoproteins are historically defined by
      their density, with low-density lipoproteins positively and high-density
      lipoproteins (HDLs) negatively associated with CVD risk in large populations.
      However, these broad definitions tend to obscure the remarkable heterogeneity
      within each class. Evidence indicates that each class is composed of physically
      (size, density, charge) and compositionally (protein and lipid) distinct
      subclasses exhibiting unique functionalities and differing effects on disease.
      HDLs in particular contain upward of 85 proteins of widely varying function that
      are differentially distributed across a broad range of particle diameters. We
      hypothesized that the plasma lipoproteins, particularly HDL, represent a
      continuum of phospholipid platforms that facilitate specific protein-protein
      interactions. To test this idea, we separated normal human plasma using three
      techniques that exploit different lipoprotein physicochemical properties (gel
      filtration chromatography, ionic exchange chromatography, and preparative
      isoelectric focusing). We then tracked the co-separation of 76 lipid-associated
      proteins via mass spectrometry and applied a summed correlation analysis to
      identify protein pairs that may co-reside on individual lipoproteins. The
      analysis produced 2701 pairing scores, with the top hits representing previously
      known protein-protein interactions as well as numerous unknown pairings. A
      network analysis revealed clusters of proteins with related functions,
      particularly lipid transport and complement regulation. The specific co
      separation of protein pairs or clusters suggests the existence of stable
      lipoprotein subspecies that may carry out distinct functions. Further
      characterization of the composition and function of these subspecies may point to
      better targeted therapeutics aimed at CVD or other diseases. 

PMID- 23882026
TI  - Quantitative phosphoproteomic study of pressure-overloaded mouse heart reveals
      dynamin-related protein 1 as a modulator of cardiac hypertrophy.
AB  - Pressure-overload stress to the heart causes pathological cardiac hypertrophy,
      which increases the risk of cardiac morbidity and mortality. However, the
      detailed signaling pathways induced by pressure overload remain unclear. Here we
      used phosphoproteomics to delineate signaling pathways in the myocardium
      responding to acute pressure overload and chronic hypertrophy in mice. Myocardial
      samples at 4 time points (10, 30, 60 min and 2 weeks) after transverse aortic
      banding (TAB) in mice underwent quantitative phosphoproteomics assay. Temporal
      phosphoproteomics profiles showed 360 phosphorylation sites with significant
      regulation after TAB. Multiple mechanical stress sensors were activated after
      acute pressure overload. Gene ontology analysis revealed differential
      phosphorylation between hearts with acute pressure overload and chronic
      hypertrophy. Most interestingly, analysis of the cardiac hypertrophy pathway
      revealed phosphorylation of the mitochondrial fission protein dynamin-related
      protein 1 (DRP1) by prohypertrophic kinases. Phosphorylation of DRP1 S622 was
      confirmed in TAB-treated mouse hearts and phenylephrine (PE)-treated rat neonatal
      cardiomyocytes. TAB-treated mouse hearts showed phosphorylation-mediated
      mitochondrial translocation of DRP1. Inhibition of DRP1 with the small-molecule
      inhibitor mdivi-1 reduced the TAB-induced hypertrophic responses. Mdivi-1 also
      prevented PE-induced hypertrophic growth and oxygen consumption in rat neonatal
      cardiomyocytes. We reveal the signaling responses of the heart to pressure stress
      in vivo and in vitro. DRP1 may be important in the development of cardiac
      hypertrophy. 

PMID- 23882027
TI  - Proteogenomic analysis of Bradyrhizobium japonicum USDA110 using GenoSuite, an
      automated multi-algorithmic pipeline.
AB  - We present GenoSuite, an integrated proteogenomic pipeline to validate, refine
      and discover protein coding genes using high-throughput mass spectrometry (MS)
      data from prokaryotes. To demonstrate the effectiveness of GenoSuite, we analyzed
      proteomics data of Bradyrhizobium japonicum (USDA110), a model organism to study
      agriculturally important rhizobium-legume symbiosis. Our analysis confirmed 31%
      of known genes, refined 49 gene models for their translation initiation site
      (TIS) and discovered 59 novel protein coding genes. Notably, a novel protein
      which redefined the boundary of a crucial cytochrome P450 system related operon
      was discovered, known to be highly expressed in the anaerobic symbiotic
      bacteroids. A focused analysis on N-terminally acetylated peptides indicated
      downstream TIS for gene blr0594. Finally, ortho-proteogenomic analysis revealed
      three novel genes in recently sequenced B. japonicum USDA6(T) genome. The
      discovery of large number of missing genes and correction of gene models have
      expanded the proteomic landscape of B. japonicum and presents an unparalleled
      utility of proteogenomic analyses and versatility of GenoSuite for annotating
      prokaryotic genomes including pathogens. 

PMID- 23882028
TI  - Development of a 5-plex SILAC method tuned for the quantitation of tyrosine
      phosphorylation dynamics.
AB  - The propagation of phosphorylation downstream of receptor tyrosine kinases is a
      key dynamic cellular event involved in signal transduction, which is often
      deregulated in disease states such as cancer. Probing phosphorylation dynamics is
      therefore crucial for understanding receptor tyrosine kinases' function and
      finding ways to inhibit their effects. MS methods combined with metabolic
      labeling such as stable isotope labeling with amino acids in cell culture (SILAC)
      have already proven successful in deciphering temporal phosphotyrosine
      perturbations. However, they are limited in terms of multiplexing, and they also
      are time consuming, because several experiments need to be performed separately.
      Here, we introduce an innovative approach based on 5-plex SILAC that allows
      monitoring of phosphotyrosine signaling perturbations induced by a drug treatment
      in one single experiment. Using this new labeling strategy specifically tailored
      for phosphotyrosines, it was possible to generate the time profiles for 318
      unique phosphopeptides belonging to 215 proteins from an erlotinib-treated breast
      cancer cell line model. Hierarchical clustering of the time profiles followed by
      pathway enrichment analysis highlighted epidermal growth factor receptor (EGFR or
      ErbB1) and ErbB2 signaling as the major pathways affected by erlotinib, thereby
      validating the method. Moreover, based on the similarity of its time profile to
      those of other proteins in the ErbB pathways, the phosphorylation at Tyr453 of
      protein FAM59A, a recently described adaptor of EGFR, was confirmed as tightly
      involved in the signaling cascade. The present investigation also demonstrates
      the remote effect of EGFR inhibition on ErbB3 phosphorylation sites such as
      Tyr1289 and Tyr1328, as well as a potential feedback effect on Tyr877 of ErbB2.
      Overall, the 5-plex SILAC is a straightforward approach that extends sample
      multiplexing and builds up the arsenal of methods for tyrosine phosphorylation
      dynamics. 

PMID- 23882029
TI  - Interrogating cAMP-dependent kinase signaling in Jurkat T cells via a protein
      kinase A targeted immune-precipitation phosphoproteomics approach.
AB  - In the past decade, mass-spectrometry-based methods have emerged for the
      quantitative profiling of dynamic changes in protein phosphorylation, allowing
      the behavior of thousands of phosphorylation sites to be monitored in a single
      experiment. However, when one is interested in specific signaling pathways, such
      shotgun methodologies are not ideal because they lack selectivity and are not
      cost and time efficient with respect to instrument and data analysis time. Here
      we evaluate and explore a peptide-centric antibody generated to selectively
      enrich peptides containing the cAMP-dependent protein kinase (PKA) consensus
      motif. This targeted phosphoproteomic strategy is used to profile temporal
      quantitative changes of potential PKA substrates in Jurkat T lymphocytes upon
      prostaglandin E2 (PGE2) stimulation, which increases intracellular cAMP,
      activating PKA. Our method combines ultra-high-specificity motif-based
      immunoaffinity purification with cost-efficient stable isotope dimethyl labeling.
      We identified 655 phosphopeptides, of which 642 (i.e. 98%) contained the
      consensus motif [R/K][R/K/X]X[pS/pT]. When our data were compared with a large
      scale Jurkat T-lymphocyte phosphoproteomics dataset containing more than 10,500
      phosphosites, a minimal overlap of 0.2% was observed. This stresses the need for
      such targeted analyses when the interest is in a particular kinase. Our data
      provide a resource of likely substrates of PKA, and potentially some substrates
      of closely related kinases. Network analysis revealed that about half of the
      observed substrates have been implicated in cAMP-induced signaling. Still, the
      other half of the here-identified substrates have been less well characterized,
      representing a valuable resource for future research. 

PMID- 23882031
TI  - Transdisciplinary electric power grid science.

PMID- 23882030
TI  - Amine-reactive neutron-encoded labels for highly plexed proteomic quantitation.
AB  - We describe a novel amine-reactive chemical label that exploits differential
      neutron-binding energy between (13)C and (15)N isotopes. These neutron-encoded
      (NeuCode) chemical labels enable up to 12-plex MS1-based protein quantification.
      Each structurally identical, but isotopically unique, tag is encoded with a 12.6
      mDa mass difference-relative to its nearest neighbor-so that peptides bearing
      these NeuCode signatures do not increase spectral complexity and are detected
      only upon analysis with very high mass-resolving powers. We demonstrate that the
      method provides quantitative performance that is comparable to both metabolic
      labeling and isobaric tagging while combining the benefits of both strategies.
      Finally, we employ the tags to characterize the proteome of Saccharomyces
      cerevisiae during the diauxic shift, a metabolic transition from fermentation to
      aerobic respiration. 

PMID- 23882033
TI  - Leclercia adecarboxylata and catheter-related bacteraemia: review of the
      literature and outcome with regard to catheters and patients.
AB  - Infection is a common complication in patients carrying a central venous catheter
      (CVC) and is associated with increased morbidity and mortality. Leclercia
      adecarboxylata is an unusual but emerging pathogen in healthy and
      immunocompromised patients. We report a case of L. adecarboxylata bacteraemia in
      a patient with a haemodialysis tunnelled CVC. In accordance with the
      susceptibility to the tested antimicrobials, a long-course treatment with
      intravenous gentamicin plus amoxicillin-clavulanic acid and gentamicin-lock
      therapy was adopted. The patient had a full recovery and the catheter was not
      removed. We also performed a systematic PubMed/Medline and Scopus review of peer
      reviewed English papers on L. adecarboxylata infections, focusing on bacteraemia
      in patients with different types of CVCs. Moreover, we suggest a treatment
      algorithm to preserve the patient and maintain the CVC. 

PMID- 23882034
TI  - Introduction to the 4th World Congress on Controversies to Consensus in Diabetes,
      Obesity and Hypertension (CODHy).

PMID- 23882035
TI  - Role of reduced beta-cell mass versus impaired beta-cell function in the
      pathogenesis of type 2 diabetes.

PMID- 23882036
TI  - Genetic screening for the risk of type 2 diabetes: worthless or valuable?

PMID- 23882038
TI  - Guideline approach to therapy in patients with newly diagnosed type 2 diabetes.

PMID- 23882039
TI  - GLP-1 effects on islets: hormonal, neuronal, or paracrine?

PMID- 23882037
TI  - Pathophysiologic approach to therapy in patients with newly diagnosed type 2
      diabetes.

PMID- 23882040
TI  - Is physical exercise a core therapeutical element for most patients with type 2
      diabetes?

PMID- 23882041
TI  - Do we still need pioglitazone for the treatment of type 2 diabetes? A risk
      benefit critique in 2013.

PMID- 23882043
TI  - Activation of GPR40 as a therapeutic target for the treatment of type 2 diabetes.
AB  - The stimulation of insulin secretion by glucose can be modulated by multiple
      nutritive, hormonal, and pharmacological inputs. Fatty acids potentiate insulin
      secretion through the generation of intracellular signaling molecules and through
      the activation of cell surface receptors. The G-protein-coupled receptor 40
      (GPR40), also known as free fatty acid receptor 1 (we will use GPR40 in this
      review), has emerged as an important component in the fatty acid augmentation of
      insulin secretion. By signaling predominantly through Galphaq/11, GPR40 increases
      intracellular calcium and activates phospholipases to generate diacylglycerols
      resulting in increased insulin secretion. Synthetic small-molecule agonists of
      GPR40 enhance insulin secretion in a glucose-dependent manner in vitro and in
      vivo with a mechanism similar to that found with fatty acids. GPR40 agonists have
      shown efficacy in increasing insulin secretion and lowering blood glucose in
      rodent models of type 2 diabetes. Recent phase I and phase II clinical trials in
      humans have shown that the GPR40 agonist TAK-875 reduces fasting and postprandial
      blood glucose and lowers HbA1c with efficacy equal to that of the sulfonylurea
      glimepiride without inducing hypoglycemia or evidence of tachyphylaxis. These
      data suggest that targeting the GPR40 receptor can be a viable therapeutic option
      for the treatment of type 2 diabetes. 

PMID- 23882044
TI  - How do we continue treatment in patients with type 2 diabetes when therapeutic
      goals are not reached with oral antidiabetes agents and lifestyle? Incretin
      versus insulin treatment.

PMID- 23882042
TI  - In vivo actions of peroxisome proliferator-activated receptors: glycemic control,
      insulin sensitivity, and insulin secretion.

PMID- 23882045
TI  - Early insulinization to prevent diabetes progression.

PMID- 23882046
TI  - Insulin as an early treatment for type 2 diabetes: ORIGIN or end of an old
      question?

PMID- 23882047
TI  - Is there evidence to support use of premixed or prandial insulin regimens in
      insulin-naive or previously insulin-treated type 2 diabetic patients?

PMID- 23882048
TI  - Intensification of insulin therapy for type 2 diabetic patients in primary care:
      basal-bolus regimen versus premix insulin analogs: when and for whom?

PMID- 23882049
TI  - Insulin pump for type 2 diabetes: use and misuse of continuous subcutaneous
      insulin infusion in type 2 diabetes.

PMID- 23882050
TI  - Combining incretin-based therapies with insulin: realizing the potential in type
      2 diabetes.

PMID- 23882051
TI  - Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic
      syndrome with cancer.

PMID- 23882052
TI  - Insulin therapy and cancer.

PMID- 23882053
TI  - Do GLP-1-based therapies increase cancer risk?

PMID- 23882054
TI  - Cardiovascular outcome studies with novel antidiabetes agents: scientific and
      operational considerations.

PMID- 23882055
TI  - Is glucose control important for prevention of cardiovascular disease in
      diabetes?

PMID- 23882056
TI  - The case for: hypoglycemia is of cardiovascular importance.

PMID- 23882057
TI  - Cardiovascular importance of hyperglycemia and hypoglycemia.

PMID- 23882058
TI  - Glycemic variability: both sides of the story.

PMID- 23882060
TI  - Defending the con side: obesity paradox does not exist.

PMID- 23882059
TI  - Obesity paradox does exist.

PMID- 23882061
TI  - Mechanism of metabolic advantages after bariatric surgery: it's all
      gastrointestinal factors versus it's all food restriction.

PMID- 23882062
TI  - Targets for body fat, blood pressure, lipids, and glucose-lowering interventions
      in healthy older people.

PMID- 23882063
TI  - Individualization of antihypertensive drug treatment.

PMID- 23882064
TI  - Ambulatory blood pressure monitoring in the diagnosis and management of
      hypertension.

PMID- 23882066
TI  - Intolerance to statins: mechanisms and management.

PMID- 23882065
TI  - Prognostic value of blood pressure variability and average blood pressure levels
      in patients with hypertension and diabetes.

PMID- 23882067
TI  - Congenital heart disease beyond the age of 60: emergence of a new population with
      high resource utilization, high morbidity, and high mortality.
AB  - AIMS: The population of adults with congenital heart disease (ACHD) is growing
      and ageing. Limited information about the diagnostic spectrum of this emerging
      population, its resource utilization at tertiary ACHD centres, and especially
      about prognostic parameters is available. METHODS AND RESULTS: Retrospective
      cohort study on all ACHD patients >=60 years of age under active follow-up. All
      cause mortality was the primary outcome measure. Out of a total population of
      7315 ACHD patients, 375 [190 females (50.7%), mean age 64.8 +/- 5.9 years]
      fulfilled the inclusion criteria. During a median follow-up of 5.5 (IQR 3.1-8.6)
      years, 55 of the 375 patients died. The number of interventions (P = 0.0006), the
      number and length of hospitalization (P < 0.0001), and the number of outpatient
      clinic visits (P < 0.0001) were significantly higher in patients >=60 compared
      with patients aged between 20 and 60 years. Patients >=60 years of age with
      moderate or severe congenital heart defects had worse survival prospects than
      their age- and gender-matched comparison population. On multivariate Cox
      analysis, coronary artery disease [hazard ratio (HR): 5.04; 95%CI: 1.88-13.51, P
      = 0.0014], symptoms of heart failure (HR: 2.36; 95%CI: 1.05-5.29, P < 0.05), NYHA
      class (HR: 1.96; 95%CI: 1.18-3.26, P < 0.01), and moderate to severe reduction in
      systemic ventricular systolic function (HR: 1.90; 95%CI: 1.20-2.99, P < 0.001)
      were the strongest prognostic factors. CONCLUSION: There is a growing number of
      elderly ACHD patients with high mortality rates and a higher utilization of
      healthcare resources compared with younger patients. Acquired morbidities, such
      as coronary artery disease, seem to be key determinants of outcome in this older
      population in conjunction with the underlying congenital heart disease.

PMID- 23882069
TI  - Ruptured giant aortocoronary vein graft aneurysm.

PMID- 23882068
TI  - Hypertensive target organ damage predicts incident diabetes mellitus.
AB  - AIMS: Whether patients with hypertensive preclinical cardiovascular disease (CVD)
      are at higher risk of incident diabetes has never been studied. METHODS AND
      RESULTS: We assessed incident diabetes in 4176 hypertensive non-diabetic patients
      (age 58.7 +/- 8.9 years, 58% male) with >=1 year follow-up (median: 3.57 years;
      inter-quartile range: 2.04-7.25). Left ventricular (LV) hypertrophy (LVH) was
      defined as LV mass index (LVMi) >=51 g/m(2.7). Carotid atherosclerosis (CA) was
      defined as intima-media thickness >1.5 mm. During follow-up, diabetes developed
      in 393 patients (9.4%), more frequently in those with than without initial LVH or
      CA (odds ratio = 1.97 and 1.67, respectively; both P < 0.0001). In the Cox
      regression, the presence of either initial LVH or CA was associated with higher
      hazard of diabetes [hazards ratio (HR) = 1.30 and 1.38, respectively; both P =
      0.03], independently of the type and number of anti-hypertensive medications,
      initial systolic blood pressure (P < 0.001), body mass index, fasting glucose,
      family history of diabetes (all P < 0.0001), and therapy with beta-blockers. The
      presence of one of the, or both, markers of preclinical CVD increased the chance
      of incident diabetes by 63 or 64%, respectively (both P < 0.002), independently
      of significant confounders, a result that was confirmed (HR = 1.70 or 1.93,
      respectively; both P < 0.0001) using ATPIII metabolic syndrome (HR = 2.73; P <
      0.0001) in the Cox model. CONCLUSION: Initial LVH and CA are significant
      predictors of new onset diabetes in a large population of treated hypertensive
      patients, independently of initial metabolic profile, anti-hypertensive therapy,
      and other significant covariates. This sequence may be attributable to risk
      factors common to preclinical CVD and diabetes, but a vascular origin of diabetes
      cannot be excluded.

PMID- 23882070
TI  - Baseline and post-surgery endothelial progenitor cell levels in patients with
      early-stage non-small-cell lung carcinoma: impact on cancer recurrence and
      survival.
AB  - OBJECTIVES: Endothelial progenitor cells (EPCs) are believed to play a role in
      promoting abnormal vascularization in neoplastic sites. We measured the number of
      circulating EPCs in treatment-naive patients with early non-small-cell lung
      cancer (NSCLC) and healthy controls. The prospective influence of baseline and
      post-surgery EPC levels on cancer recurrence and survival was investigated.
      METHODS: Circulating EPCs were quantified by FACS analysis in 34 patients with
      Stage I-II NSCLC and 68 healthy age- and sex-matched controls. Measurement of
      EPCs was repeated 48 h after thoracic surgery and at the hospital discharge.
      Cancer recurrence and survival was evaluated after 446 +/- 106 days of follow-up
      (range 182-580 days). RESULTS: The base 10 logarithmic [log] number of
      circulating EPCs was comparable between patients with NSCLC and controls [mean +/
      standard deviation (SD): 2.3 +/- 0.32 vs 2.3 +/- 0.26 n/ml, P = 0.776]. In
      regression analysis, smoking status [standardized coefficient beta (beta) = 
      0.26, 95% confidence interval (CI) for B -0.29/-0.03, P = 0.014] and systolic
      blood pressure [beta = -0.23, 95% CI for B -0.011/-0.001, P = 0.018] were
      independent predictors of the number of EPCs, irrespective of the NSCLC status.
      The mean number of EPCs did not change after surgical treatment. However, a post
      surgery EPC increase was observed in 44% patients. Patients with a 48 h post
      surgery EPC increase had a higher rate of cancer recurrence/death than patients
      with either stable or decreased post-surgery EPC levels [hazard ratio (HR) 4.4,
      95% CI 1.1-17.3; P = 0.032], irrespective of confounders. CONCLUSIONS:
      Circulating EPC levels are comparable between patients with early-stage NSCLC and
      healthy controls. Overall, surgical cancer resection was not associated with a
      significant early EPC change. However, an early post-surgery EPC increase is able
      to predict an increased risk of cancer recurrence and death.

PMID- 23882071
TI  - Reply to Petricevic et al.

PMID- 23882072
TI  - Dynamic determination of the functional state in photolyase and the implication
      for cryptochrome.
AB  - The flavin adenine dinucleotide cofactor has an unusual bent configuration in
      photolyase and cryptochrome, and such a folded structure may have a functional
      role in initial photochemistry. Using femtosecond spectroscopy, we report here
      our systematic characterization of cyclic intramolecular electron transfer (ET)
      dynamics between the flavin and adenine moieties of flavin adenine dinucleotide
      in four redox forms of the oxidized, neutral, and anionic semiquinone, and
      anionic hydroquinone states. By comparing wild-type and mutant enzymes, we have
      determined that the excited neutral oxidized and semiquinone states absorb an
      electron from the adenine moiety in 19 and 135 ps, whereas the excited anionic
      semiquinone and hydroquinone states donate an electron to the adenine moiety in
      12 ps and 2 ns, respectively. All back ET dynamics occur ultrafast within 100 ps.
      These four ET dynamics dictate that only the anionic hydroquinone flavin can be
      the functional state in photolyase due to the slower ET dynamics (2 ns) with the
      adenine moiety and a faster ET dynamics (250 ps) with the substrate, whereas the
      intervening adenine moiety mediates electron tunneling for repair of damaged DNA.
      Assuming ET as the universal mechanism for photolyase and cryptochrome, these
      results imply anionic flavin as the more attractive form of the cofactor in the
      active state in cryptochrome to induce charge relocation to cause an
      electrostatic variation in the active site and then lead to a local conformation
      change to initiate signaling. 

PMID- 23882073
TI  - Statistical significance of combinatorial regulations.
AB  - More than three transcription factors often work together to enable cells to
      respond to various signals. The detection of combinatorial regulation by multiple
      transcription factors, however, is not only computationally nontrivial but also
      extremely unlikely because of multiple testing correction. The exponential growth
      in the number of tests forces us to set a strict limit on the maximum arity.
      Here, we propose an efficient branch-and-bound algorithm called the "limitless
      arity multiple-testing procedure" (LAMP) to count the exact number of testable
      combinations and calibrate the Bonferroni factor to the smallest possible value.
      LAMP lists significant combinations without any limit, whereas the family-wise
      error rate is rigorously controlled under the threshold. In the human breast
      cancer transcriptome, LAMP discovered statistically significant combinations of
      as many as eight binding motifs. This method may contribute to uncover pathways
      regulated in a coordinated fashion and find hidden associations in heterogeneous
      data. 

PMID- 23882074
TI  - Single-particle analysis reveals shutoff control of the Arabidopsis ammonium
      transporter AMT1;3 by clustering and internalization.
AB  - Ammonium is a preferred source of nitrogen for plants but is toxic at high
      levels. Plant ammonium transporters (AMTs) play an essential role in NH4(+)
      uptake, but the mechanism by which AMTs are regulated remains unclear. To study
      how AMTs are regulated in the presence of ammonium, we used variable-angle total
      internal reflection fluorescence microscopy and fluorescence cross-correlation
      spectroscopy for single-particle fluorescence imaging of EGFP-tagged AMT1;3 on
      the plasma membrane of Arabidopsis root cells at various ammonium levels. We
      demonstrated that AMT1;3-EGFP dynamically appeared and disappeared on the plasma
      membrane as moving fluorescent spots in low oligomeric states under N-deprived
      and N-sufficient conditions. Under external high-ammonium stress, however, AMT1;3
      EGFPs were found to amass into clusters, which were then internalized into the
      cytoplasm. A similar phenomenon also occurred in the glutamine synthetase mutant
      gln1;2 background. Single-particle analysis of AMT1;3-EGFPs in the clathrin heavy
      chain 2 mutant (chc2 mutant) and Flotllin1 artificial microRNA (Flot1 amiRNA)
      backgrounds, together with chemical inhibitor treatments, demonstrated that the
      endocytosis of AMT1;3 clusters induced by high-ammonium stress could occur mainly
      through clathrin-mediated endocytic pathways, but the contribution of microdomain
      associated endocytic pathway cannot be excluded in the internalization. Our
      results revealed that the clustering and endocytosis of AMT1;3 provides an
      effective mechanism by which plant cells can avoid accumulation of toxic levels
      of ammonium by eliminating active AMT1;3 from the plasma membrane. 

PMID- 23882076
TI  - Multiparametric approach for the evaluation of lipid nanoparticles for siRNA
      delivery.
AB  - Nanoparticle-mediated siRNA delivery is a complex process that requires transport
      across numerous extracellular and intracellular barriers. As such, the
      development of nanoparticles for efficient delivery would benefit from an
      understanding of how parameters associated with these barriers relate to the
      physicochemical properties of nanoparticles. Here, we use a multiparametric
      approach for the evaluation of lipid nanoparticles (LNPs) to identify
      relationships between structure, biological function, and biological activity.
      Our results indicate that evaluation of multiple parameters associated with
      barriers to delivery such as siRNA entrapment, pKa, LNP stability, and cell
      uptake as a collective may serve as a useful prescreening tool for the
      advancement of LNPs in vivo. This multiparametric approach complements the use of
      in vitro efficacy results alone for prescreening and improves in vitro-in vivo
      translation by minimizing false negatives. For the LNPs used in this work, the
      evaluation of multiple parameters enabled the identification of LNP pKa as one of
      the key determinants of LNP function and activity both in vitro and in vivo. It
      is anticipated that this type of analysis can aid in the identification of
      meaningful structure-function-activity relationships, improve the in vitro
      screening process of nanoparticles before in vivo use, and facilitate the future
      design of potent nanocarriers. 

PMID- 23882077
TI  - Importance of lipid-pore loop interface for potassium channel structure and
      function.
AB  - Potassium (i.e., K(+)) channels allow for the controlled and selective passage of
      potassium ions across the plasma membrane via a conserved pore domain. In voltage
      gated K(+) channels, gating is the result of the coordinated action of two
      coupled gates: an activation gate at the intracellular entrance of the pore and
      an inactivation gate at the selectivity filter. By using solid-state NMR
      structural studies, in combination with electrophysiological experiments and
      molecular dynamics simulations, we show that the turret region connecting the
      outer transmembrane helix (transmembrane helix 1) and the pore helix behind the
      selectivity filter contributes to K(+) channel inactivation and exhibits a
      remarkable structural plasticity that correlates to K(+) channel inactivation.
      The transmembrane helix 1 unwinds when the K(+) channel enters the inactivated
      state and rewinds during the transition to the closed state. In addition to well
      characterized changes at the K(+) ion coordination sites, this process is
      accompanied by conformational changes within the turret region and the pore
      helix. Further spectroscopic and computational results show that the same channel
      domain is critically involved in establishing functional contacts between pore
      domain and the cellular membrane. Taken together, our results suggest that the
      interaction between the K(+) channel turret region and the lipid bilayer exerts
      an important influence on the selective passage of potassium ions via the K(+)
      channel pore. 

PMID- 23882078
TI  - Increased transmissibility explains the third wave of infection by the 2009 H1N1
      pandemic virus in England.
AB  - In the 2009 H1N1 pandemic, the United Kingdom experienced two waves of infection,
      the first in the late spring and the second in the autumn. Given the low level of
      susceptibility to the pandemic virus expected to be remaining in the population
      after the second wave, it was a surprise that a substantial third epidemic
      occurred in the UK population between November 2010 and February 2011, despite no
      evidence for any significant antigenic evolution of the pandemic virus. Here, we
      use a mathematical model of influenza transmission embedded within a Bayesian
      synthesis inferential framework to jointly analyze syndromic, virological, and
      serological surveillance data collected in England in 2009-2011 and thereby
      assess epidemiological mechanisms which might have generated the third wave. We
      find that substantially increased transmissibility of the H1N1pdm09 virus is
      required to reproduce the third wave, suggesting that the virus evolved and
      increased fitness in the human host by the end of 2010, or that the very cold
      weather experienced in the United Kingdom at that time enhanced transmission
      rates. We also find some evidence that the preexisting heterologous immunity
      which reduced attack rates in adults during 2009 had substantially decayed by the
      winter of 2010, thus increasing the susceptibility of the adult population to
      infection. Finally, our analysis suggests that a pandemic vaccination campaign
      targeting adults and school-age children could have mitigated or prevented the
      third wave even at moderate levels of coverage. 

PMID- 23882080
TI  - Determining complete electron flow in the cofactor photoreduction of oxidized
      photolyase.
AB  - The flavin cofactor in photoenzyme photolyase and photoreceptor cryptochrome may
      exist in an oxidized state and should be converted into reduced state(s) for
      biological functions. Such redox changes can be efficiently achieved by
      photoinduced electron transfer (ET) through a series of aromatic residues in the
      enzyme. Here, we report our complete characterization of photoreduction dynamics
      of photolyase with femtosecond resolution. With various site-directed mutations,
      we identified all possible electron donors in the enzyme and determined their ET
      timescales. The excited cofactor behaves as an electron sink to draw electron
      flow from a series of encircling aromatic molecules in three distinct layers from
      the active site in the center to the protein surface. The dominant electron flow
      follows the conserved tryptophan triad in a hopping pathway across the layers
      with multiple tunneling steps. These ET dynamics occur ultrafast in less than 150
      ps and are strongly coupled with local protein and solvent relaxations. The
      reverse electron flow from the flavin is slow and in the nanosecond range to
      ensure high reduction efficiency. With 12 experimentally determined elementary ET
      steps and 6 ET reaction pairs, the enzyme exhibits a distinct reduction-potential
      gradient along the same aromatic residues with favorable reorganization energies
      to drive a highly unidirectional electron flow toward the active-site center from
      the protein surface. 

PMID- 23882081
TI  - Macrophage migration inhibitory factor (MIF) is a critical mediator of the innate
      immune response to Mycobacterium tuberculosis.
AB  - Macrophage migration inhibitory factor (MIF), an innate cytokine encoded in a
      functionally polymorphic genetic locus, contributes to detrimental inflammation
      but may be crucial for controlling infection. We explored the role of variant MIF
      alleles in tuberculosis. In a Ugandan cohort, genetic low expressers of MIF were
      2.4-times more frequently identified among patients with Mycobacterium
      tuberculosis (TB) bacteremia than those without. We also found mycobacteria
      stimulated transcription of MIF and serum MIF levels to be correlated with MIF
      genotype in human macrophages and in a separate cohort of US TB patients,
      respectively. To determine mechanisms for MIF's protective role, we studied both
      aerosolized and i.v. models of mycobacterial infection and observed MIF-deficient
      mice to succumb more quickly with higher organism burden, increased lung
      pathology, and decreased innate cytokine production (TNF-alpha, IL-12, IL-10).
      MIF-deficient animals showed increased pulmonary neutrophil accumulation but
      preserved adaptive immune response. MIF-deficient macrophages demonstrated
      decreased cytokine and reactive oxygen production and impaired mycobacterial
      killing. Transcriptional investigation of MIF-deficient macrophages revealed
      reduced expression of the pattern recognition receptor dectin-1; restoration of
      dectin-1 expression recovered innate cytokine production and mycobacterial
      killing. Our data place MIF in a crucial upstream position in the innate immune
      response to mycobacteria and suggest that commonly occurring low expression MIF
      alleles confer an increased risk of TB disease in some populations. 

PMID- 23882082
TI  - Monovalent antibody design and mechanism of action of onartuzumab, a MET
      antagonist with anti-tumor activity as a therapeutic agent.
AB  - Binding of hepatocyte growth factor (HGF) to the receptor tyrosine kinase MET is
      implicated in the malignant process of multiple cancers, making disruption of
      this interaction a promising therapeutic strategy. However, targeting MET with
      bivalent antibodies can mimic HGF agonism via receptor dimerization. To address
      this limitation, we have developed onartuzumab, an Escherichia coli-derived,
      humanized, and affinity-matured monovalent monoclonal antibody against MET,
      generated using the knob-into-hole technology that enables the antibody to engage
      the receptor in a one-to-one fashion. Onartuzumab potently inhibits HGF binding
      and receptor phosphorylation and signaling and has antibody-like pharmacokinetics
      and antitumor activity. Biochemical data and a crystal structure of a ternary
      complex of onartuzumab antigen-binding fragment bound to a MET extracellular
      domain fragment, consisting of the MET Sema domain fused to the adjacent Plexins,
      Semaphorins, Integrins domain (MET Sema-PSI), and the HGF beta-chain demonstrate
      that onartuzumab acts specifically by blocking HGF alpha-chain (but not beta
      chain) binding to MET. These data suggest a likely binding site of the HGF alpha
      chain on MET, which when dimerized leads to MET signaling. Onartuzumab,
      therefore, represents the founding member of a class of therapeutic monovalent
      antibodies that overcomes limitations of antibody bivalency for targets impacted
      by antibody crosslinking. 

PMID- 23882085
TI  - Atrial septal dissection and left-to-right shunt after mitral valve replacement:
      assessment with real-time three-dimensional transoesophageal echocardiography.

PMID- 23882084
TI  - Cost of rNTP/dNTP pool imbalance at the replication fork.
AB  - The concentration of ribonucleoside triphosphates (rNTPs) in cells is far greater
      than the concentration of deoxyribonucleoside triphosphates (dNTPs), and this
      pool imbalance presents a challenge for DNA polymerases (Pols) to select their
      proper substrate. This report examines the effect of nucleotide pool imbalance on
      the rate and fidelity of the Escherichia coli replisome. We find that rNTPs
      decrease replication fork rate by competing with dNTPs at the active site of the
      C-family Pol III replicase at a step that does not require correct base-pairing.
      The effect of rNTPs on Pol rate generalizes to B-family eukaryotic replicases,
      Pols delta and epsilon. Imbalance of the dNTP pool also slows the replisome and
      thus is not specific to rNTPs. We observe a measurable frequency of rNMP
      incorporation that predicts one rNTP incorporated every 2.3 kb during chromosome
      replication. Given the frequency of rNMP incorporation, the repair of rNMPs is
      likely rapid. RNase HII nicks DNA at single rNMP residues to initiate replacement
      with dNMP. Considering that rNMPs will mark the new strand, RNase HII may direct
      strand-specificity for mismatch repair (MMR). How the newly synthesized strand is
      recognized for MMR is uncertain in eukaryotes and most bacteria, which lack a
      methyl-directed nicking system. Here we demonstrate that Bacillus subtilis
      incorporates rNMPs in vivo, that RNase HII plays a role in their removal, and the
      RNase HII gene deletion enhances mutagenesis, suggesting a possible role of
      incorporated rNMPs in MMR. 

PMID- 23882083
TI  - Activation-induced cytidine deaminase (AID) is necessary for the epithelial
      mesenchymal transition in mammary epithelial cells.
AB  - Activation-induced cytidine deaminase (AID), which functions in antibody
      diversification, is also expressed in a variety of germ and somatic cells.
      Evidence that AID promotes DNA demethylation in epigenetic reprogramming
      phenomena, and that it is induced by inflammatory signals, led us to investigate
      its role in the epithelial-mesenchymal transition (EMT), a critical process in
      normal morphogenesis and tumor metastasis. We find that expression of AID is
      induced by inflammatory signals that induce the EMT in nontransformed mammary
      epithelial cells and in ZR75.1 breast cancer cells. shRNA-mediated knockdown of
      AID blocks induction of the EMT and prevents cells from acquiring invasive
      properties. Knockdown of AID suppresses expression of several key EMT
      transcriptional regulators and is associated with increased methylation of CpG
      islands proximal to the promoters of these genes; furthermore, the DNA
      demethylating agent 5 aza-2'deoxycytidine (5-Aza-dC) antagonizes the effects of
      AID knockdown on the expression of EMT factors. We conclude that AID is necessary
      for the EMT in this breast cancer cell model and in nontransformed mammary
      epithelial cells. Our results suggest that AID may act near the apex of a
      hierarchy of regulatory steps that drive the EMT, and are consistent with this
      effect being mediated by cytosine demethylation. This evidence links our findings
      to other reports of a role for AID in epigenetic reprogramming and control of
      gene expression. 

PMID- 23882086
TI  - Economy and Nobel prizes: cause behind chocolate and milk?

PMID- 23882087
TI  - Upper spine morphology in hypophosphatemic rickets and healthy controls: a
      radiographic study.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to describe upper spine
      morphology in adult patients with hypophosphatemic rickets (HR) compared with
      controls to assess differences in spine morphology in terms of severity of
      skeletal impact and to study associations between spine morphology and
      craniofacial morphology. MATERIAL/METHODS: The study population comprised 36 HR
      patients and 49 controls. The atlas and axis dimensions were measured on
      cephalograms, and the differences between the groups were estimated by regression
      analysis. The upper spine morphology was visually assessed to estimate the
      prevalence of cervical vertebral anomalies. RESULTS: The dimensions of the atlas
      and the axis were larger in HR patients than in controls (P <= 0.001), and
      fusions (FUS) occurred more often in HR patients (39%) than in controls (6%; P <=
      0.001). In HR patients, the length of the atlas correlated positively (P = 0.008)
      and the height of the dens correlated negatively (P = 0.043) with the severity of
      skeletal impact. The height of the posterior arch of the atlas and the length of
      the axis correlated negatively with the cranial base angle (P <= 0.017), and the
      vertical dimensions of the atlas correlated positively with the thickness of the
      occipital skull (P <= 0.015). The length of the atlas correlated positively with
      mandibular prognathism (P = 0.042). FUS correlated positively with the frontal
      and parietal thickness (P = 0.034 and P = 0.003, respectively). CONCLUSIONS: The
      dimension of the atlas and the axis and the prevalence of the FUS were increased
      in HR patients compared with controls. Upper spine dimensions were associated
      with craniofacial dimensions, primarily in relation to the posterior cranial
      fossa.

PMID- 23882088
TI  - Effects of various analgesics on the level of prostaglandin E2 during orthodontic
      tooth movement.
AB  - AIM: The aim of this double-blind, randomized, placebo-controlled clinical study
      was to evaluate the analgesic effects of preoperative/postoperative ibuprofen and
      acetaminophen use after bonding and to find a relation between the pain level and
      the amount of prostaglandin released. MATERIALS AND METHODS: Forty-eight patients
      were included and randomly divided to three equal groups that received either
      ibuprofen, acetaminophen or placebo for pain relief. The pain levels were
      measured before bonding, after bonding, at first, second, third, and seventh days
      on a 100 mm visual analogue scale (VAS) and gingival crevicular fluid (GCF)
      samples were collected at the same time intervals to measure the amount of
      prostaglandin E2 (PGE2) released. PGE2 levels were determined with ELISA test.
      The results were evaluated with Wilcoxon and Kruskal-Wallis tests with Bonferroni
      correction. RESULTS: Acetaminophen and placebo groups showed similar pain levels
      during the first 2 days, whereas ibuprofen group showed lower pain levels during
      the first day after bonding. PGE2 levels did not show statistically significant
      difference in time within the analgesic groups. No significant relation between
      the pain perceived and PGE2 released was found. LIMITATIONS: The biggest
      limitation of this study is the subjective nature of pain and its method of
      evaluation. CONCLUSIONS: The perception of pain by patients taking ibuprofen and
      acetaminophen at pre/post appliance placement was not different from patients
      taking placebo. No time-related differences in PGE2 level were found between the
      groups and no significant correlation was found between the perception of pain
      and PGE2 levels.

PMID- 23882089
TI  - Cognitive debiasing 1: origins of bias and theory of debiasing.
AB  - Numerous studies have shown that diagnostic failure depends upon a variety of
      factors. Psychological factors are fundamental in influencing the cognitive
      performance of the decision maker. In this first of two papers, we discuss the
      basics of reasoning and the Dual Process Theory (DPT) of decision making. The
      general properties of the DPT model, as it applies to diagnostic reasoning, are
      reviewed. A variety of cognitive and affective biases are known to compromise the
      decision-making process. They mostly appear to originate in the fast intuitive
      processes of Type 1 that dominate (or drive) decision making. Type 1 processes
      work well most of the time but they may open the door for biases. Removing or at
      least mitigating these biases would appear to be an important goal. We will also
      review the origins of biases. The consensus is that there are two major sources:
      innate, hard-wired biases that developed in our evolutionary past, and acquired
      biases established in the course of development and within our working
      environments. Both are associated with abbreviated decision making in the form of
      heuristics. Other work suggests that ambient and contextual factors may create
      high risk situations that dispose decision makers to particular biases. Fatigue,
      sleep deprivation and cognitive overload appear to be important determinants. The
      theoretical basis of several approaches towards debiasing is then discussed. All
      share a common feature that involves a deliberate decoupling from Type 1
      intuitive processing and moving to Type 2 analytical processing so that
      eventually unexamined intuitive judgments can be submitted to verification. This
      decoupling step appears to be the critical feature of cognitive and affective
      debiasing. 

PMID- 23882090
TI  - Science to practice: will contrast agents for molecular imaging of angiogenesis
      help overcome the limitations of functional vascular imaging?
AB  - Schmieder and colleagues introduced a new molecular magnetic resonance (MR) probe
      with a promising lipophilic gadolinium chelate complex that provides high
      relaxivity. Results of in vivo experiments clearly demonstrate the excellence of
      the probe for longitudinally monitoring alpha(v)beta(3) integrin expression in
      tumors. In addition, the authors have developed a robust nonrelaxometric analysis
      method with which to quantify the spatial distribution of molecular MR probes. In
      combination with a molecular probe targeting angiogenesis, this approach may be
      superior to functional vascular assessments. It has the potential to enable
      better detection of angiogenic regions in heterogeneous tumors and to improve the
      monitoring and individualization of antiangiogenic treatments.

PMID- 23882091
TI  - The story behind the image.

PMID- 23882093
TI  - Apparent diffusion coefficient and beyond: what diffusion MR imaging can tell us
      about tissue structure.

PMID- 23882094
TI  - Fuller Albright, postmenopausal osteoporosis, and fish vertebrae.

PMID- 23882095
TI  - Screening for early detection of breast cancer: overdiagnosis versus suboptimal
      patient management.

PMID- 23882096
TI  - The use of MR imaging in treatment planning for patients with rectal carcinoma:
      have you checked the "DISTANCE"?
AB  - Rectal cancer is a common and serious disease in the Western hemisphere. Optimal
      treatment of rectal cancer involves a multidisciplinary approach, with
      collaboration required between radiologists, oncologists, surgeons, and
      pathologists to achieve local control and decrease the rate of recurrence.
      Several studies have been published that show the ability to accurately stage
      rectal cancer with magnetic resonance (MR) imaging. Moreover, advances in
      preoperative therapies require accurate preoperative staging with MR imaging to
      select those patients who may benefit from more intensive treatment, without
      subjecting those who will not benefit to unnecessary treatment. As we enter an
      era of individualized patient care, stratified according to the risk of both
      local and distant failure, imaging takes on the same importance as the tumor type
      and genetic susceptibility. MR imaging is now an essential tool to enable the
      oncology team to make appropriate treatment decisions. However, rectal cancer
      evaluation with MR imaging remains a challenge in the hands of nonexperts. This
      article describes a mnemonic device, "DISTANCE," to enable a systematic approach
      to the interpretation of MR images, thereby enabling all the clinically relevant
      features to be adequately assessed: DIS, for Distance from the Inferior part of
      the tumor to the transitional Skin; T, for T staging; A, for Anal complex; N, for
      Nodal staging; C, for Circumferential resection margin; and E, for Extramural
      vascular invasion.

PMID- 23882098
TI  - Case 196: Immunoglobulin G4-related disease.

PMID- 23882099
TI  - Abbreviations in request forms.

PMID- 23882100
TI  - Diagnostic performance of CT angiography in patients with atrial fibrillation.

PMID- 23882101
TI  - Role of biomarkers in the diagnosis of mild traumatic brain injury.

PMID- 23882102
TI  - Interpreting the accuracy of clinical predictors of head CT abnormal findings in
      nontrauma patients.

PMID- 23882103
TI  - Predictors of reintubation in critically ill patients.
AB  - BACKGROUND: Assessment of a patient's readiness for removal of the endotracheal
      tube in the ICU is based on respiratory, airway, and neurological measures.
      However, nearly 20% of patients require reintubation. We created a prediction
      model for the need for reintubation, which incorporates variables importantly
      contributing to extubation failure. METHODS: This was a cohort study of 2,007
      endotracheally intubated subjects who required ICU admission at a tertiary care
      center. Data collection included demographic, hemodynamic, respiratory, and
      neurological variables preceding extubation. Data were compared between subjects
      extubated successfully and those who required reintubation, using bivariate
      logistic regression models, with the binary outcome reintubation and the baseline
      characteristics as predictors. Multivariable logistic regression analysis with
      robust variance was used to build the prediction model. RESULTS: Of the 2,007
      subjects analyzed, 376 (19%) required reintubation. In the bivariate analysis,
      admission Simplified Acute Physiology Score II, minute ventilation, breathing
      frequency, oxygenation, number of prior SBTs, rapid shallow breathing index,
      airway-secretions suctioning frequency and quantity, heart rate, and diastolic
      blood pressure differed significantly between the extubation success and failure
      groups. In the multivariable analysis, higher Simplified Acute Physiology Score
      II and suctioning frequency were associated with failed extubation. The area
      under the receiver operating characteristic curve was 0.68 for failure at any
      time, and 0.71 for failure within 24 hours. However, prior failed SBT, minute
      ventilation, and diastolic blood pressure were additional independent predictors
      of failure at any time, whereas oxygenation predicted extubation failure within
      24 hours. CONCLUSIONS: A small number of independent variables explains a
      substantial portion of the variability of extubation failure, and can help
      identify patients at high risk of needing reintubation. These characteristics
      should be incorporated in the decision-making process of ICU extubation.

PMID- 23882104
TI  - Assessment of central airway obstruction using impulse oscillometry before and
      after interventional bronchoscopy.
AB  - BACKGROUND: Spirometry is used to physiologically assess patients with central
      airway obstruction (CAO) before and after interventional bronchoscopy, but is not
      always feasible in these patients, does not localize the anatomic site of
      obstruction, and may not correlate with the patient's functional impairment.
      Impulse oscillometry may overcome these limitations. We assessed the correlations
      between impulse oscillometry measurements, symptoms, and type of airway
      narrowing, before and after interventional bronchoscopy, and whether impulse
      oscillometry parameters can discriminate between fixed and dynamic CAO. METHODS:
      Twenty consecutive patients with CAO underwent spirometry, impulse oscillometry,
      computed tomography, dyspnea assessment, and bronchoscopy, before and after
      interventional bronchoscopy. The collapsibility index (the percent difference in
      airway lumen diameter during expiration versus during inspiration) was calculated
      using morphometric bronchoscopic images during quiet breathing. Variable CAO was
      defined as a collapsibility index of > 50%. Fixed CAO was defined as a
      collapsibility index of < 50%. The degree of obstruction was analyzed with
      computed tomography measurements. RESULTS: After interventional bronchoscopy, all
      impulse oscillometry measurements significantly improved, especially resistance
      at 5 Hz, which decreased from 0.67 +/- 0.29kPa/L/s to 0.38 +/- 0.17kPa/L/s (P <
      .001), and reactance at 20 Hz, which increased from -0.09 +/- 0.11 to 0.03 +/-
      0.08 (P < .001). Changes in dyspnea score correlated with resistance at 5 Hz, the
      difference between the resistance at 5 Hz and the resistance at 20 Hz, and the
      reactance at 5 Hz, but not with spirometry measurements. The type of obstruction
      also correlated with dyspnea score, and showed distinct impulse oscillometry
      measurements. CONCLUSIONS: Impulse oscillometry measurements correlate with
      symptom improvements after interventional bronchoscopy. Impulse oscillometry
      might be useful to discriminate variable from fixed central airway obstruction.
      (University Hospital Medical Information Network, http://www.umin.ac.jp/english,
      ID000005322).

PMID- 23882105
TI  - Evaluation of blind nasotracheal suctioning and non-bronchoscopic mini
      bronchoalveolar lavage in critically ill patients with infectious pneumonia: a
      preliminary study.
AB  - BACKGROUND: We evaluated the diagnostic performance and safety of combined blind
      nasotracheal suctioning and non-bronchoscopic mini-bronchoalveolar lavage (mini
      BAL) to obtain respiratory secretion specimens from spontaneously breathing, non
      intubated patients with infectious pneumonia in intensive care. METHODS: Patients
      suspected of having infectious pneumonia were included prospectively. Three
      samples were obtained: expectorated sputum, nasotracheal suctioning, and mini-BAL
      via a double telescopic catheter (Combicath). Under local anesthesia,
      nasotracheal suctioning was done according to standard recommendations. Then mini
      BAL was performed; the bronchial catheter serves as a guide for the mini-BAL
      catheter, and tracheal position is verified via colorimetric capnography.
      RESULTS: We included 36 subjects (29 men, median age 69 y, median Simplified
      Acute Physiology Score II 32), of which 32 (89%) underwent nasotracheal
      suctioning and mini-BAL, and from 13 (36%) we collected expectorated sputum.
      Based on colorimetric capnography confirmation of the tracheal position, 75%
      (24/32) of the successful combined procedures were achieved on the first attempt.
      The median duration of the combined procedure was 7 min. Bacterial pneumonia was
      diagnosed in 24/36 (67%) subjects, among whom 21 (88%) had undergone successful
      nasotracheal suctioning and mini-BAL, respectively, for 8/21 (38% [95% CI 0.17
      0.58%] and 14/21 (67% [95% CI 0.46-0.86%]). Mini-BAL diagnosed a significantly
      higher percentage of bacterial pneumonias than did nasotracheal suctioning.
      Expectorated sputum yielded no diagnoses. CONCLUSIONS: Blind nasotracheal
      suctioning confirmed via colorimetric capnography allows microbiological
      diagnosis, and can be enhanced by non-bronchoscopic mini-BAL. Colorimetric
      capnography helps confirm bronchial tube position. Non-bronchoscopic mini-BAL is
      a novel and feasible way to collect bronchial secretions without fibroscopy.
      (ClinicalTrials.gov NCT00763620.).

PMID- 23882106
TI  - Meditative movement for respiratory function: a systematic review.
AB  - BACKGROUND: Meditative movement, such as tai chi, yoga, and qi gong, may benefit
      people with cystic fibrosis (CF), as a form of gentle exercise incorporating
      meditation, breathing, and relaxation. Respiratory function is the most common
      issue in CF. In this systematic review we synthesized the evidence on the effect
      of meditative movement on respiratory function in patients with CF. METHODS: We
      searched Chinese and English language databases with terms relating to tai
      chi/yoga/qi gong, and respiratory function/cough/dyspnea. Articles were screened
      and selected by 2 researchers. We included controlled studies published in
      English or Chinese after 1980, and extracted data using a specially designed
      spreadsheet. Two researchers independently evaluated study quality and reporting,
      using 3 standardized checklists. Meta-analysis was not possible due to
      heterogeneous methods. RESULTS: We found 1,649 papers, included 43 (30 in
      English, 13 in Chinese), 23 of which were randomized controlled trials, and 20
      were non-randomized trials. No studies were concerned with CF. Eleven studies
      included patients with respiratory disorders, and 27 included healthy people.
      Very few studies were high quality. The main problems with the randomized
      controlled trials was the randomization and non-random and/or poorly reported
      sampling. The main problems with the non-randomized studies were poor reporting
      of samples and non-equivalent groups. Although no clinically important changes
      were found, meditative movement may improve FEV1 in healthy people, compared to
      no treatment/exercise (the intervention groups showed effect-size changes from
      0.07 to 0.83), but meditative movement did not appear to affect FEV1/FVC in
      subjects with COPD. Key study limitations were: poor reporting of sampling or
      methods; inadequate sample size; non-randomized design; inadequate description of
      randomization; randomization by center; no blinding; lack of reporting of
      important aspects of meditative movement; and short-term follow-up. CONCLUSIONS:
      The available evidence does not support meditative movement for patients with CF,
      and there is very limited evidence for respiratory function in healthy
      populations. The available studies had heterogeneous populations and provided
      inadequate sampling information, so clinically relevant conclusions cannot be
      drawn. Well powered, randomized studies of meditative movement are needed.

PMID- 23882107
TI  - Effectiveness of controlled breathing techniques on anxiety and depression in
      hospitalized patients with COPD: a randomized clinical Trial.
AB  - BACKGROUND: Anxiety and depression are prevalent comorbidities in patients with
      COPD. Breathing techniques can improve anxiety and depression in patients
      hospitalized for COPD exacerbation. METHODS: We conducted a randomized clinical
      study with 46 male subjects, 67-86 years old, hospitalized with acute COPD
      exacerbation. Subjects were randomly and equally divided into a control group and
      a controlled breathing intervention group. We measured baseline and post
      intervention dyspnea, anxiety and depression, quality of life (with the St
      George's Respiratory Questionnaire and the European Quality of Life
      questionnaire), maximum inspiratory and expiratory pressure, hand-grip strength,
      and sleep quality. The cohort had high dyspnea and low overall quality of life.
      RESULTS: Controlled breathing techniques significantly improved dyspnea, anxiety,
      and mobility. All the measured variables improved in the intervention group. The
      control group had poorer values in all the variables after the hospitalization
      period. CONCLUSIONS: Controlled breathing exercises improve anxiety and
      depression in patients hospitalized for COPD exacerbation. (ClinicalTrials.gov
      NCT01826682).

PMID- 23882108
TI  - The effect of a mechanical ventilation discontinuation protocol in patients with
      simple and difficult weaning: impact on clinical outcomes.
AB  - OBJECTIVE: We sought to determine whether the utilization of a respiratory
      therapist (RT) driven mechanical ventilation weaning protocol is associated with
      improvement in clinical outcomes in subjects with simple versus difficult
      weaning. METHODS: This was a retrospective analysis of prospectively collected
      data obtained during a quality improvement project. We collected data on 803
      consecutive mechanically ventilated patients admitted to the ICU of an academic
      tertiary care hospital. We compared an RT-driven weaning protocol to a physician
      driven weaning strategy. RESULTS: Of the 803 patients, 651 with simple weaning
      and 131 with difficult weaning were included in the analysis. In the subjects
      with simple weaning, 514 (79%) were weaned with the RT-driven protocol. Among the
      difficult weaning subjects, 101(77.1%) were liberated with the RT-driven
      protocol. A multivariate analysis, which included Acute Physiology and Chronic
      Health Evaluation II, body mass index, and type of primary ICU team under which
      the subjects were admitted, revealed a significant difference in ventilator-free
      days at 28-days, which supports the RT-driven protocol over the physician-driven
      strategy. Specifically, the RT-driven protocol increased ventilator-free days by
      20.92% and 68.2% among subjects with simple and difficult weaning, respectively.
      A multivariate analysis of ICU mortality and extubation failure found no
      significant difference between the RT-driven protocol and the physician-driven
      strategy. CONCLUSIONS: The RT-driven weaning protocol increased ventilator-free
      days among subjects with simple and difficult weaning, with no significant
      differences in ICU mortality or extubation failure.

PMID- 23882109
TI  - Importance of inhaler device use status in the control of asthma in adults: the
      asthma inhaler treatment study.
AB  - BACKGROUND: Proper education and training in correct inhalation technique has
      been reported to have a substantial role in the achievement of optimal
      therapeutic benefit and asthma control. The present study was designed to
      evaluate inhaler technique and the role of education in relation to asthma
      control among patients with persistent asthma in Turkey. METHODS: A total of 572
      patients with persistent asthma (mean +/- SD age 42.7 +/- 12.2 y, 76% females)
      were included in this non-interventional, observational, registry study conducted
      across Turkey. Data on the effective and correct use of inhaler devices were
      collected via the Ease of Use for the Inhaler Device Questionnaire to patients
      and physicians. RESULTS: Asthma control (overall 61.5% at baseline, and increased
      to 87.3% during follow-up) was better, with significant improvement in technique
      and decrease in basic errors to the range 0-1, regardless of the inhaler type.
      Overall, the most common basic error associated with inhalation maneuvers was
      failure to exhale before inhaling through the device (18.9%). There was
      concordance between the patients and physicians in the ratio of correct inhaler
      technique only for spray-type inhalers. CONCLUSIONS: Close follow-up with
      repeated checking of the patient's inhaler technique and correction of errors
      each time by a physician seem to be associated with a significant decrease in the
      percent of patients who make basic errors in inhalation maneuvers and device
      independent errors, and with better control of persistent asthma.

PMID- 23882110
TI  - Primary male osteoporosis is associated with enhanced glucocorticoid
      availability.
AB  - OBJECTIVE: While systemic glucocorticoids compromise bone metabolism, altered
      intracellular cortisol availability may also contribute to the pathogenesis of
      primary male osteoporosis (MO). The objective of this study was to assess whether
      intracellular cortisol availability is increased in MO due to a distorted local
      cortisol metabolism. METHODS: Forty-one patients with MO were compared with age-
      and BMI-matched non-osteoporotic subjects after excluding overt systemic
      hypercortisolism (N = 41). Cortisol, cortisone and the respective tetrahydro-,
      5alpha-tetrahydro- and total cortisol metabolites were analysed by GC-MS in 24 h
      urine. Apparent 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzyme
      activities, excretion of cortisol metabolites and calcium, and fractional urinary
      calcium excretion were assessed and related to BMD. RESULTS: Fractional and total
      urinary calcium excretion negatively correlated with BMD at all (P < 0.05) and at
      three of five (P < 0.05) measurement sites, respectively. While systemic cortisol
      was unchanged, apparent 11beta-HSD enzyme activity in MO patients (P < 0.01)
      suggested increased intracellular cortisol availability. Total and fractional
      urinary calcium excretion was higher, with apparent 11beta-HSD enzyme activities
      consistent with an enhanced intracellular cortisol availability (P < 0.05).
      CONCLUSION: Apparent 11beta-HSD enzyme activities consistent with increased
      intracellular cortisol availability correlated with urinary calcium loss and
      reduced bone mineral density in MO. The changes in 11beta-HSD activity were
      associated with both the fractional calcium excretion, suggesting altered renal
      calcium handling, and the absolute urinary calcium excretion. Both mechanisms
      could result in a marked bone calcium deficiency if insufficiently compensated
      for by intestinal calcium uptake.

PMID- 23882111
TI  - From endocrine to rheumatism: do gut hormones play roles in rheumatoid arthritis?
AB  - RA is characterized by chronic inflammation in the musculoskeletal system, in
      which TNF-alpha is the key cytokine trigger. TNF-alpha, previously known as
      cachectin, is implicated in the modulation of body composition and energy
      expenditure. Gut hormones, including acyl ghrelin, des-acyl ghrelin, GIP, GLP-1
      and PYY, have been known to be the major regulators of appetite, nutrition,
      energy expenditure and body mass formation. Emerging evidence indicates that
      blockade of TNF-alpha by biologics not only ameliorates rheumatoid inflammation,
      but can affect the secretion and action of gut hormones on appetite, body
      composition, energy expenditure, muscle catabolism and bone remodelling. A link
      between the gastrointestinal endocrine axis and the immune system may be
      established through the interaction of proinflammatory cytokines, including TNF
      alpha and these gut hormones. With the ever-increasing understanding of
      rheumatoid inflammation and the invention of more biologics to modulate the
      cytokine network, more attention should be given to the possible immunomodulatory
      roles of gut hormones in autoimmune inflammatory reactions.

PMID- 23882112
TI  - The impact of age, biogenesis, and genomic clustering on Drosophila microRNA
      evolution.
AB  - The molecular evolutionary signatures of miRNAs inform our understanding of their
      emergence, biogenesis, and function. The known signatures of miRNA evolution have
      derived mostly from the analysis of deeply conserved, canonical loci. In this
      study, we examine the impact of age, biogenesis pathway, and genomic arrangement
      on the evolutionary properties of Drosophila miRNAs. Crucial to the accuracy of
      our results was our curation of high-quality miRNA alignments, which included
      nearly 150 corrections to ortholog calls and nucleotide sequences of the global
      12-way Drosophilid alignments currently available. Using these data, we studied
      primary sequence conservation, normalized free-energy values, and types of
      structure-preserving substitutions. We expand upon common miRNA evolutionary
      patterns that reflect fundamental features of miRNAs that are under functional
      selection. We observe that melanogaster-subgroup-specific miRNAs, although
      recently emerged and rapidly evolving, nonetheless exhibit evolutionary
      signatures that are similar to well-conserved miRNAs and distinct from other
      structured noncoding RNAs and bulk conserved non-miRNA hairpins. This provides
      evidence that even young miRNAs may be selected for regulatory activities. More
      strikingly, we observe that mirtrons and clustered miRNAs both exhibit distinct
      evolutionary properties relative to solo, well-conserved miRNAs, even after
      controlling for sequence depth. These studies highlight the previously
      unappreciated impact of biogenesis strategy and genomic location on the
      evolutionary dynamics of miRNAs, and affirm that miRNAs do not evolve as a
      unitary class. 

PMID- 23882113
TI  - Predicted group II intron lineages E and F comprise catalytically active
      ribozymes.
AB  - Group II introns are self-splicing, retrotransposable ribozymes that contribute
      to gene expression and evolution in most organisms. The ongoing identification of
      new group II introns and recent bioinformatic analyses have suggested that there
      are novel lineages, which include the group IIE and IIF introns. Because the
      function and biochemical activity of group IIE and IIF introns have never been
      experimentally tested and because these introns appear to have features that
      distinguish them from other introns, we set out to determine if they were indeed
      self-splicing, catalytically active RNA molecules. To this end, we transcribed
      and studied a set of diverse group IIE and IIF introns, quantitatively
      characterizing their in vitro self-splicing reactivity, ionic requirements, and
      reaction products. In addition, we used mutational analysis to determine the
      relative role of the EBS-IBS 1 and 2 recognition elements during splicing by
      these introns. We show that group IIE and IIF introns are indeed distinct active
      intron families, with different reactivities and structures. We show that the
      group IIE introns self-splice exclusively through the hydrolytic pathway, while
      group IIF introns can also catalyze transesterifications. Intriguingly, we
      observe one group IIF intron that forms circular intron. Finally, despite an
      apparent EBS2-IBS2 duplex in the sequences of these introns, we find that this
      interaction plays no role during self-splicing in vitro. It is now clear that the
      group IIE and IIF introns are functional ribozymes, with distinctive properties
      that may be useful for biotechnological applications, and which may contribute to
      the biology of host organisms. 

PMID- 23882115
TI  - Templates and existing elements and models for implementation of patient exposure
      tracking.
AB  - There is wide interest currently in patient exposure tracking. This paper
      provides templates for implementation of tracking at the practice (hospital)
      level, multi-practice level, national level and international level. It provides
      suggestions for implementation in less-resourced countries. It includes elements
      such as patient identifier, dose quantities that should be covered and how to
      make sense from dose figures, availability of digital imaging and communications
      in medicine files with dose information or structured dose reports and
      capabilities of picture archiving and communication system (PACS). While tracking
      at several hospitals in a country connected by PACS and nationwide PACS is also a
      reality, tracking at the international level is currently a challenge. Guidance
      provided in this paper will facilitate its implementation at all levels. 

PMID- 23882114
TI  - The double-stranded RNA binding domain of human Dicer functions as a nuclear
      localization signal.
AB  - Dicer is a key player in microRNA (miRNA) and RNA interference (RNAi) pathways,
      processing miRNA precursors and double-stranded RNA into ~21-nt-long products
      ultimately triggering sequence-dependent gene silencing. Although processing of
      substrates in vertebrate cells occurs in the cytoplasm, there is growing evidence
      suggesting Dicer is also present and functional in the nucleus. To address this
      possibility, we searched for a nuclear localization signal (NLS) in human Dicer
      and identified its C-terminal double-stranded RNA binding domain (dsRBD) as
      harboring NLS activity. We show that the dsRBD-NLS can mediate nuclear import of
      a reporter protein via interaction with importins beta, 7, and 8. In the context
      of full-length Dicer, the dsRBD-NLS is masked. However, duplication of the dsRBD
      localizes the full-length protein to the nucleus. Furthermore, deletion of the N
      terminal helicase domain results in partial accumulation of Dicer in the nucleus
      upon leptomycin B treatment, indicating that CRM1 contributes to nuclear export
      of Dicer. Finally, we demonstrate that human Dicer has the ability to shuttle
      between the nucleus and the cytoplasm. We conclude that Dicer is a shuttling
      protein whose steady-state localization is cytoplasmic. 

PMID- 23882116
TI  - General practitioners' cluster: a model to reorient primary health care to public
      health services.

PMID- 23882117
TI  - Public health services provided in the framework of general practitioners'
      clusters.

PMID- 23882118
TI  - Human resources development for the operation of general practitioners' cluster.

PMID- 23882120
TI  - Transglutaminase-catalyzed protein-protein cross-linking suppresses the activity
      of the NF-kappaB-like transcription factor relish.
AB  - Cross-linking of proteins by mammalian transglutaminases (TGs) plays important
      roles in physiological phenomena such as blood coagulation and skin formation. We
      show that Drosophila TG suppressed innate immune signaling in the gut. RNA
      interference (RNAi) directed against TG reduced the life span of flies reared
      under conventional nonsterile conditions but not of those raised under germ-free
      conditions. In conventionally reared flies, TG RNAi enhanced the expression of
      genes encoding antimicrobial peptides in the immune deficiency (IMD) pathway.
      Wild-type flies that ingested gut lysates prepared from conventionally reared TG
      RNAi-treated flies had shorter life spans. In conventionally reared flies, TG
      RNAi triggered apoptosis in the gut and induced the nuclear translocation of
      Relish, the NF-kappaB (nuclear factor kappaB)-like transcription factor of the
      IMD pathway. Wild-type flies that ingested synthetic amine donors, which inhibit
      the TG-catalyzed protein-protein cross-linking reaction, showed nuclear
      translocation of Relish and enhanced expression of genes encoding IMD-controlled
      antimicrobial peptide genes in the gut. We conclude that TG-catalyzed Relish
      cross-linking suppressed the IMD signaling pathway to enable immune tolerance
      against commensal microbes. 

PMID- 23882121
TI  - Superresolution microscopy reveals nanometer-scale reorganization of inhibitory
      natural killer cell receptors upon activation of NKG2D.
AB  - Natural killer (NK) cell responses are regulated by a dynamic equilibrium between
      activating and inhibitory receptor signals at the immune synapse (or interface)
      with target cells. Although the organization of receptors at the immune synapse
      is important for appropriate integration of these signals, there is little
      understanding of this in detail, because research has been hampered by the
      limited resolution of light microscopy. Through the use of superresolution single
      molecule fluorescence microscopy to reveal the organization of the NK cell
      surface at the single-protein level, we report that the inhibitory receptor
      KIR2DL1 is organized in nanometer-scale clusters at the surface of human resting
      NK cells. Nanoclusters of KIR2DL1 became smaller and denser upon engagement of
      the activating receptor NKG2D, establishing an unexpected crosstalk between
      activating receptor signals and the positioning of inhibitory receptors. These
      rearrangements in the nanoscale organization of surface NK cell receptors were
      dependent on the actin cytoskeleton. Together, these data establish that NK cell
      activation involves a nanometer-scale reorganization of surface receptors, which
      in turn affects models for signal integration and thresholds that control NK cell
      effector functions and NK cell development. 

PMID- 23882122
TI  - A versatile toolkit to produce sensitive FRET biosensors to visualize signaling
      in time and space.
AB  - Genetically encoded, ratiometric biosensors based on fluorescence resonance
      energy transfer (FRET) are powerful tools to study the spatiotemporal dynamics of
      cell signaling. However, many biosensors lack sensitivity. We present a biosensor
      library that contains circularly permutated mutants for both the donor and
      acceptor fluorophores, which alter the orientation of the dipoles and thus better
      accommodate structural constraints imposed by different signaling molecules while
      maintaining FRET efficiency. Our strategy improved the brightness and dynamic
      range of preexisting RhoA and extracellular signal-regulated protein kinase (ERK)
      biosensors. Using the improved RhoA biosensor, we found micrometer-sized zones of
      RhoA activity at the tip of F-actin bundles in growth cone filopodia during
      neurite extension, whereas RhoA was globally activated throughout collapsing
      growth cones. RhoA was also activated in filopodia and protruding membranes at
      the leading edge of motile fibroblasts. Using the improved ERK biosensor, we
      simultaneously measured ERK activation dynamics in multiple cells using low
      magnification microscopy and performed in vivo FRET imaging in zebrafish. Thus,
      we provide a construction toolkit consisting of a vector set, which enables
      facile generation of sensitive biosensors. 

PMID- 23882123
TI  - Nonaggressive and adapted social cognition is controlled by the interplay between
      noradrenergic and nicotinic receptor mechanisms in the prefrontal cortex.
AB  - Social animals establish flexible behaviors and integrated decision-making
      processes to adapt to social environments. Such behaviors are impaired in all
      major neuropsychiatric disorders and depend on the prefrontal cortex (PFC). We
      previously showed that nicotinic acetylcholine receptors (nAChRs) and
      norepinephrine (NE) in the PFC are necessary for mice to show adapted social
      cognition. Here, we investigated how the cholinergic and NE systems converge
      within the PFC to modulate social behavior. We used a social interaction task
      (SIT) in C57BL/6 mice and mice lacking beta2*nAChRs (beta2(-/-) mice), making use
      of dedicated software to analyze >20 social sequences and pinpoint social
      decisions. We performed specific PFC NE depletions before SIT and measured
      monoamines and acetylcholine (ACh) levels in limbic corticostriatal circuitry.
      After PFC-NE depletion, C57BL/6 mice exhibited impoverished and more rigid social
      behavior and were 6-fold more aggressive than sham-lesioned animals, whereas
      beta2(-/-) mice showed unimpaired social behavior. Our biochemical measures
      suggest a critical involvement of DA in SIT. In addition, we show that the
      balance between basal levels of monoamines and of ACh modulates aggressiveness
      and this modulation requires functional beta2*nAChRs. These findings demonstrate
      the critical interplay between prefrontal NE and nAChRs for the development of
      adapted and nonaggressive social cognition.

PMID- 23882124
TI  - The role of HCA2 (GPR109A) in regulating macrophage function.
AB  - We investigated the novel role of HCA2 (GPR109A) and its ligand nicotinic acid in
      regulating macrophage function. Hca2 expression in the RAW264.7 murine macrophage
      cell line is strongly induced by LPS treatment and correlates with the expression
      of TNF-alpha. Treatment with 300 MUM nicotinic acid (reported EC50 3 MUM, peak
      plasma concentration 50-300 MUM), significantly inhibited TNF-alpha, IL-6, IL
      12p40, and IL-1beta production (P<0.05) in LPS (1 ng/ml)-stimulated wild-type
      murine bone marrow-derived macrophages (BMMs) but failed to do so in Hca2(-/-)
      BMMs. Treatment with nicotinic acid reduced nuclear factor kappaB (NF-kappaB)
      activation levels by 43% (P<0.03) in wild-type BMMs 6 h after LPS stimulation but
      not in Hca2(-/-) BMMs. Nicotinic acid significantly inhibited wild-type BMM
      chemotaxis (P<0.001), but had no effect on the chemotaxis of Hca2(-/-) BMMs. A
      significant increase in low-density lipoprotein uptake by both wild-type
      (P<0.006) and Hca2(-/-) BMMs (P<0.03) in response to LPS was observed, which was
      significantly suppressed by nicotinic acid in wild-type BMMs (P<0.04) but not in
      Hca2(-/-) BMMs. Our results suggest that the nicotinic acid-HCA2 axis is a novel
      negative regulator of macrophage activation.

PMID- 23882125
TI  - Disruption of TSC1/2 signaling complex reveals a checkpoint governing thymic CD4+
      CD25+ Foxp3+ regulatory T-cell development in mice.
AB  - Thymic-derived CD4(+)CD25(+)Foxp3(+) natural regulatory T (nTreg) cells are
      essential for the maintenance of peripheral immune tolerance. Signaling pathways
      that drive immature thymic progenitors to differentiate into
      CD4(+)CD25(+)Foxp3(+) nTreg cells need to be elucidated. The precise role of the
      TSC1/2 complex, a critical negative regulator of mammalian target of rapamycin
      (mTOR), in thymic CD4(+)CD25(+)Foxp3(+) nTreg-cell development remains elusive.
      In the present study, we found that the percentage and cell number of thymic
      CD4(+)CD25(+)Foxp3(+) nTreg cells were significantly increased in T-cell-specific
      TSC1-knockout (TSC1KO) mice. Nevertheless, the levels of CD4(+)CD25(+)Foxp3(-)
      nTreg precursors in TSC1KO thymus were indistinguishable from those in wild-type
      mice. TSC1KO CD4(+)CD25(+)Foxp3(+) nTreg cells showed normal cell death but
      enhanced proliferative response to IL-2 in a STAT5-dependent manner. Rapamycin
      (Rapa) treatment failed to rescue but rather increased the frequency of
      CD4(+)CD25(+)Foxp3(+) nTreg cells in TSC1KO and RictorKO mice. The percentage and
      cell number of thymic CD4(+)CD25(+)Foxp3(+) nTreg cells were significantly
      increased in T-cell-specific RictorKO mice but not in PtenKO mice. Collectively,
      our studies suggest that TSC1 plays an important role in regulating thymic
      CD4(+)CD25(+)Foxp3(+) nTreg-cell development via a Rapa-resistant and mTORC2
      dependent signaling pathway.

PMID- 23882126
TI  - Mechanisms enforcing the estrogen receptor beta selectivity of botanical
      estrogens.
AB  - Because little is known about the actions of botanical estrogens (BEs), widely
      consumed by menopausal women, we investigated the mechanistic and cellular
      activities of some major BEs. We examined the interactions of genistein,
      daidzein, equol, and liquiritigenin with estrogen receptors ERalpha and ERbeta,
      with key coregulators (SRC3 and RIP140) and chromatin binding sites, and the
      regulation of gene expression and proliferation in MCF-7 breast cancer cells
      containing ERalpha and/or ERbeta. Unlike the endogenous estrogen, estradiol (E2),
      BEs preferentially bind to ERbeta, but their ERbeta-potency selectivity in gene
      stimulation (340- to 830-fold vs. E2) is enhanced at several levels (coregulator
      recruitment, chromatin binding); nevertheless, at high (0.1 or 1 MUM)
      concentrations, BEs also fully activate ERalpha. Because ERalpha drives breast
      cancer cell proliferation and ERbeta dampens this, the relative levels of these
      two ERs in target cells and the BE dose greatly affect gene expression and
      proliferative response and will be crucial determinants of the potential benefits
      vs. risks of BEs. Our findings reveal key and novel mechanistic differences in
      the estrogenic activities of BEs vs. E2, with BEs displaying patterns of activity
      distinctly different from those seen with E2 and provide valuable information to
      inform future studies.

PMID- 23882127
TI  - Distinct molecular targets including SLO-1 and gap junctions are engaged across a
      continuum of ethanol concentrations in Caenorhabditis elegans.
AB  - Ethanol (alcohol) interacts with diverse molecular effectors across a range of
      concentrations in the brain, eliciting intoxication through to sedation.
      Invertebrate models including the nematode worm Caenorhabditis elegans have been
      deployed for molecular genetic studies to inform on key components of these
      alcohol signaling pathways. C. elegans studies have typically employed external
      dosing with high (>250 mM) ethanol concentrations: A careful analysis of
      responses to low concentrations is lacking. Using the C. elegans pharyngeal
      system as a paradigm, we report a previously uncharacterized continuum of
      cellular and behavioral responses to ethanol from low (10 mM) to high (300 mM)
      concentrations. The complexity of these responses indicates that the pleiotropic
      action of ethanol observed in mammalian brain is conserved in this invertebrate
      model. We investigated two candidate ethanol effectors, the calcium-activated
      K(+) channel SLO-1 and gap junctions, and show that they contribute to, but are
      not sole determinants of, the low- and high-concentration effects, respectively.
      Notably, this study shows cellular and whole organismal behavioral responses to
      ethanol in C. elegans that directly equate to intoxicating through to supralethal
      blood alcohol concentrations in humans and provides an important benchmark for
      interpretation of paradigms that seek to inform on human alcohol use disorders.

PMID- 23882128
TI  - Structure, transcription, and variability of metazoan mitochondrial genome:
      perspectives from an unusual mitochondrial inheritance system.
AB  - Despite its functional conservation, the mitochondrial genome (mtDNA) presents
      strikingly different features among eukaryotes, such as size, rearrangements, and
      amount of intergenic regions. Nonadaptive processes such as random genetic drift
      and mutation rate play a fundamental role in shaping mtDNA: the mitochondrial
      bottleneck and the number of germ line replications are critical factors, and
      different patterns of germ line differentiation could be responsible for the
      mtDNA diversity observed in eukaryotes. Among metazoan, bivalve mollusc mtDNAs
      show unusual features, like hypervariable gene arrangements, high mutation rates,
      large amount of intergenic regions, and, in some species, an unique inheritance
      system, the doubly uniparental inheritance (DUI). The DUI system offers the
      possibility to study the evolutionary dynamics of mtDNAs that, despite being in
      the same organism, experience different genetic drift and selective pressures. We
      used the DUI species Ruditapes philippinarum to study intergenic mtDNA functions,
      mitochondrial transcription, and polymorphism in gonads. We observed: 1) the
      presence of conserved functional elements and novel open reading frames (ORFs)
      that could explain the evolutionary persistence of intergenic regions and may be
      involved in DUI-specific features; 2) that mtDNA transcription is lineage
      specific and independent from the nuclear background; and 3) that male
      transmitted and female-transmitted mtDNAs have a similar amount of polymorphism
      but of different kinds, due to different population size and selection
      efficiency. Our results are consistent with the hypotheses that mtDNA evolution
      is strongly dependent on the dynamics of germ line formation, and that the
      establishment of a male-transmitted mtDNA lineage can increase male fitness
      through selection on sperm function. 

PMID- 23882130
TI  - beta4GalT6 is involved in the synthesis of lactosylceramide with less intensity
      than beta4GalT5.
AB  - Glycosphingolipids are expressed on the cell membrane and act as important
      factors in various events that occur across the plasma membrane. Lactosylceramide
      (LacCer) is synthesized from glucosylceramide and is a common precursor of
      various glycosphingolipids existing in whole body. Based on the enzyme
      purification, beta1,4-galactosyltransferase 6 (B4galt6) cDNA was isolated as a
      LacCer synthase-coding gene in the rat brain. We generated B4galt6 gene knockout
      (KO) mice and analyzed their phenotypes to examine roles of beta4GalT6. B4galt6
      KO mice were born and grew up apparently normal. LacCer synthase activity and the
      composition of acidic glycosphingolipids in the brain were almost equivalent or
      minimally different between wild-type and KO mice. Studies by mouse embryonic
      fibroblasts (MEFs) revealed that the silencing of B4galt5 gene resulted in the
      marked reduction in LacCer synthase activity and this reduction was more severe
      in MEFs derived from B4galt6 KO mice than those from wild-type mice. These
      results suggested that beta4GalT6 plays a role as a LacCer synthase, whereas
      beta4GalT5 acts as a main enzyme for LacCer biosynthesis in these tissues and
      cells. 

PMID- 23882129
TI  - Recent recombination events in the core genome are associated with adaptive
      evolution in Enterococcus faecium.
AB  - Reasons for the rising clinical impact of the bacterium Enterococcus faecium
      include the species' rapid acquisition of adaptive genetic elements. Here, we
      focused on the impact of recombination on the evolution of E. faecium. We used
      the recently developed BratNextGen algorithm to detect recombinant regions in the
      core genome of 34 E. faecium strains, including three newly sequenced clinical
      strains. Recombination was found to have a significant impact on the E. faecium
      genome: of the original 1.2 million positions in the core genome, 0.5 million
      were predicted to have been affected by recombination in at least one strain.
      Importantly, strains in one of the two major E. faecium clades (clade B), which
      contains most of the E. faecium human gut commensals, formed the most important
      reservoir for donating foreign DNA to the second major E. faecium clade (clade
      A), which contains most of the clinical isolates. Also, several genomic regions
      were found to mainly recombine in specific hospital-associated E. faecium
      strains. One of these regions (the epa-like locus) likely encodes the
      biosynthesis of cell wall polysaccharides. These findings suggest a crucial role
      for recombination in the emergence of E. faecium as a successful hospital
      associated pathogen. 

PMID- 23882131
TI  - Evaluating school-community health in Cyprus.
AB  - This article presents results from the Cypriot experience of participation in a
      pan European health promotion project called 'Shape Up'. Implemented between
      September 2007 and June 2008, the aims of the overall programme reflect the
      primary concern of health promotion to facilitate healthy choices by creating the
      necessary conditions for their enactment. We describe the processes used in Shape
      Up before reporting findings from the evaluation undertaken by the University of
      Hull, UK. Findings from the Cypriot case studies demonstrate schools' potential
      to work in health promoting ways by enabling school communities to create
      environments conducive to health, where individuals are better able to take care
      of their health rather than simply implementing healthy activities at school.
      Participants in Shape Up Cyprus increased their access to healthier foods and
      opportunities to be active during and after school. Apart from visible
      environmental changes, participants were equipped with skills and critical
      knowledge to be healthier and more active citizens. They investigated the wider
      determinants of health and options for health improvement in specific contexts.
      They identified what needed changing within and around the school, developing
      visions of how changes could be enacted. They transferred visions into actions by
      writing letters, undertaking research, developing networks and accessing advice
      and financial support. We conclude that increasing awareness of the impact of
      structural factors upon health and the acquisition of skills in community action
      were central to Shape Up's success in Cyprus, and are therefore relevant for
      school-based health promotion.

PMID- 23882132
TI  - Highly efficient in vivo delivery of PMO into regenerating myotubes and rescue in
      laminin-alpha2 chain-null congenital muscular dystrophy mice.
AB  - Phosphorodiamidate morpholino oligomer (PMO)-mediated exon skipping is among the
      more promising approaches to the treatment of several neuromuscular disorders
      including Duchenne muscular dystrophy. The main weakness of this approach arises
      from the low efficiency and sporadic nature of the delivery of charge-neutral PMO
      into muscle fibers, the mechanism of which is unknown. In this study, to test our
      hypothesis that muscle fibers take up PMO more efficiently during myotube
      formation, we induced synchronous muscle regeneration by injection of cardiotoxin
      into the tibialis anterior muscle of Dmd exon 52-deficient mdx52 and wild-type
      mice. Interestingly, by in situ hybridization, we detected PMO mainly in
      embryonic myosin heavy chain-positive regenerating fibers. In addition, we showed
      that PMO or 2'-O-methyl phosphorothioate is taken up efficiently into C2C12
      myotubes when transfected 24-72 h after the induction of differentiation but is
      poorly taken up into undifferentiated C2C12 myoblasts suggesting efficient uptake
      of PMO in the early stages of C2C12 myotube formation. Next, we tested the
      therapeutic potential of PMO for laminin-alpha2 chain-null dy(3K)/dy(3K) mice: a
      model of merosin-deficient congenital muscular dystrophy (MDC1A) with active
      muscle regeneration. We confirmed the recovery of laminin-alpha2 chain and
      slightly prolonged life span following skipping of the mutated exon 4 in
      dy(3K)/dy(3K) mice. These findings support the idea that PMO entry into fibers is
      dependent on a developmental stage in myogenesis rather than on dystrophinless
      muscle membranes and provide a platform for developing PMO-mediated therapies for
      a variety of muscular disorders, such as MDC1A, that involve active muscle
      regeneration. 

PMID- 23882133
TI  - The Wage Effects of Personal Smoking History.
AB  - Why do we observe a wage differential between smokers and non-smokers? Pooling
      reports of current and prior smoking activity across 15 years from the Panel
      Study of Income Dynamics (PSID) allows the reconstruction of individual smoking
      histories. Dividing the sample into smoking history groups, the four largest of
      which are: persistent smokers, never smokers, former smokers, and future quitters
      reveals that there is no observed wage gap between former smokers and those who
      have never smoked. There is, however, a wage gap between those smokers who will
      continue smoking and three other groups of individuals: (1) those smokers who
      will quit smoking in the future, (2) those smokers who have quit smoking already,
      and (3) those who never smoked. The wage gap between smokers and non-smokers,
      observed in the 1986 cross-section, is largely driven by those who persist as
      smokers, 1986-2001. These results support the hypothesis that the cross-sectional
      wage differential is not driven by smoking per se, but may be driven by a non
      causal explanation. One plausible interpretation is that a common factor such as
      myopia, leads to reduced investment in both health capital or firm-specific or
      other human capital.

PMID- 23882134
TI  - Non-linear Growth Models in Mplus and SAS.
AB  - Non-linear growth curves or growth curves that follow a specified non-linear
      function in time enable researchers to model complex developmental patterns with
      parameters that are easily interpretable. In this paper we describe how a variety
      of sigmoid curves can be fit using the Mplus structural modeling program and the
      non-linear mixed-effects modeling procedure NLMIXED in SAS. Using longitudinal
      achievement data collected as part of a study examining the effects of preschool
      instruction on academic gain we illustrate the procedures for fitting growth
      models of logistic, Gompertz, and Richards functions. Brief notes regarding the
      practical benefits, limitations, and choices faced in the fitting and estimation
      of such models are included.

PMID- 23882135
TI  - Genetic heterogeneity and consanguinity lead to a "double hit": homozygous
      mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa.
AB  - PURPOSE: Retinitis pigmentosa (RP), the most genetically heterogeneous disorder
      in humans, actually represents a group of pigmentary retinopathies characterized
      by night blindness followed by visual-field loss. RP can appear as either
      syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher
      syndrome, characterized by the combination of RP, hearing loss, and vestibular
      dysfunction. METHODS: The underlying cause of the appearance of syndromic and
      nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab
      family was studied with whole-genome homozygosity mapping followed by whole exome
      sequencing. RESULTS: THE FAMILY WAS FOUND TO SEGREGATE NOVEL MUTATIONS OF TWO
      DIFFERENT GENES: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and
      phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B),
      which causes nonsyndromic RP. One affected child was homozygous for both
      mutations. Since the retinal phenotype seen in this patient results from
      overlapping pathologies, one might expect to find severe retinal degeneration.
      Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at
      a young age (9 months). However, this early diagnosis may be biased, as two of
      his older siblings had already been diagnosed, leading to increased awareness. At
      the age of 32 months, he had relatively good vision with normal visual fields.
      Further testing of visual function and structure at different ages in the three
      siblings is needed to determine whether the two RP-causing genes mutated in this
      youngest sibling confer increased disease severity. CONCLUSIONS: This report
      further supports the genetic heterogeneity of RP, and demonstrates how
      consanguinity could increase intrafamilial clustering of multiple hereditary
      diseases. Moreover, this report provides a unique opportunity to study the
      clinical implications of the coexistence of pathogenic mutations in two RP
      causative genes in a human patient.

PMID- 23882136
TI  - Genetic variations and polymorphisms in the ezrin gene are associated with age
      related cataract.
AB  - PURPOSE: Age-related cataract (ARC) is a complex multifactorial disorder,
      including genetic and environmental factors. Ezrin (EZR), a member of the
      ezrin/radixin/moesin (ERM) protein family, plays a crucial role in the
      development of the lens as a plasma membrane-cytoskeleton linker. We conducted
      this study to investigate the role of genetic variations of ezrin and the
      relationship between single nucleotide polymorphisms (SNPs) in EZR and
      susceptibility to ARC in a Chinese population. METHODS: A total of 205 sporadic
      age-related cataract patients and 218 unrelated random healthy controls
      participated in our study. Genomic DNA was extracted from peripheral blood
      leukocytes. All exons of EZR were sequenced after being amplified with polymerase
      chain reaction. The functional consequences of the mutations were analyzed using
      PolyPhen2. SNP statistical analysis was performed using SNPstats. RESULTS: We
      found three novel variations in 205 patients. None presented in the 218 controls,
      including c.441C>G, c.924G>C, and c.1503G>A. PolyPhen2 predicted that the
      c.924G>C mutation probably had pathogenicity. Compared with the healthy controls,
      the rs5881286 -/GT genotype and - allele frequencies (p=0.0012; odds ratio
      [OR]=3.37; 95% confidence interval [CI]=1.70-6.70; p=3.96e-5; chi(2)=18.98,
      respectively), rs2242318 T/C genotype and C allele frequencies (p=0.0045;
      OR=3.40; 95% CI=1.70-6.79; p=8.82e-6; chi(2)=21.86, respectively), and
      rs144581330 A/G genotype and G allele frequencies (p=0.0472; OR=14.46; 95%
      CI=1.29-162.43; p=0.0244, chi(2)=6.99, respectively) were higher in the patients
      with age-related cataract. SNP rs144581330 in exon 2 was also predicted to be
      probably damaging by PolyPhen2. Haplotype association including the - allele of
      rs5881286, C allele of rs2242318, and A allele of rs144581330 exhibited
      significantly higher distribution in the patients with ARC (p=8.0e-4; OR=3.38;
      95% CI=1.66-6.87). CONCLUSIONS: This study suggests that the genetic variations
      and SNPs in the gene EZR possibly contribute to the development of age-related
      cataracts in the Chinese population.

PMID- 23882137
TI  - Trypsin-mediated enzymatic degradation of type II collagen in the human vitreous.
AB  - PURPOSE: Aging of the vitreous body can result in sight-threatening pathology.
      One aspect of vitreous aging is liquefaction, which results from the vanishing of
      collagen fibrils. We investigated the possibility that trypsins are involved in
      vitreous type II collagen degradation. METHODS: Immunohistochemistry and western
      blotting were used for detecting and locating trypsin isoforms in the vitreous
      and retina of human donor eyes. The capability of the retina to produce these
      trypsins was analyzed with polymerase chain reaction. Whether the different
      trypsins degraded type II collagen was tested in vitro. The sizes of the in vitro
      induced type II collagen degradation products were compared to those present in
      the vitreous of human eyes of different ages. RESULTS: Trypsin-1 and trypsin-2
      were detected in the vitreous. In the retina, messenger ribonucleic acid (mRNA)
      coding for trypsin-2, -3, and -4 was present. Using immunohistochemistry, trypsin
      2 was detected in microglial cells located in the vitreous and the retina. All
      trypsin isoforms degraded type II collagen and produced degradation products of
      similar sizes as those present in the vitreous. CONCLUSIONS: Trypsin-1 and
      trypsin-2 appear to have a function in the degradation of vitreous type II
      collagen. They could therefore have a role in the development of vitreous
      liquefaction.

PMID- 23882138
TI  - Shrinking the room for invasive mechanical ventilation in acute chronic
      hypercapnic respiratory failure: yes, but must be sure to have opened windows for
      noninvasive ventilation.

PMID- 23882139
TI  - Anti-inflammatory effects of silver-polyvinyl pyrrolidone (Ag-PVP) nanoparticles
      in mouse macrophages infected with live Chlamydia trachomatis.
AB  - Chlamydia trachomatis is a very common sexually transmissible infection in both
      developing and developed countries. A hallmark of C. trachomatis infection is the
      induction of severe inflammatory responses which play critical roles in its
      pathogenesis. Antibiotics are the only treatment option currently available for
      controlling C. trachomatis infection; however, they are efficacious only when
      administered early after an infection. The objectives of this study are to
      explore alternative strategies in the control and regulation of inflammatory
      responses triggered by a C. trachomatis infection. We employed silver-polyvinyl
      pyrrolidone (Ag-PVP) nanoparticles, which have been shown to possess anti
      inflammatory properties, as our target and the in vitro mouse J774 macrophage
      model of C. trachomatis infection. Our hypothesis is that small sizes of Ag-PVP
      nanoparticles will control inflammatory mediators triggered by a C. trachomatis
      infection. Cytotoxicity studies using Ag-PVP nanoparticles of 10, 20, and 80 nm
      sizes revealed >80% macrophage viability up to a concentration of 6.25 MUg/mL,
      with the 10 nm size being the least toxic. All sizes of Ag-PVP nanoparticles,
      especially the 10 nm size, reduced the levels of the prototypic cytokines, tumor
      necrosis factor (TNF) and interleukin (IL)-6, as elicited from C. trachomatis
      infected macrophages. Additionally, Ag-PVP nanoparticles (10 nm) selectively
      inhibited a broad spectrum of other cytokines and chemokines produced by infected
      macrophages. Of significance, Ag-PVP nanoparticles (10 nm) caused perturbations
      in a variety of upstream (toll like receptor 2 [TLR2], nucleotide-binding
      oligomerization-protein 2 [NOD2], cluster of differentiation [CD]40, CD80, and
      CD86) and downstream (IL-1 receptor-associated kinase 3 [IRAK3] and matrix
      metallopeptidase 9 [MMP9]) inflammatory signaling pathways by downregulating
      their messenger ribonucleic acid (mRNA) gene transcript expressions as induced by
      C. trachomatis in macrophages. Collectively, our data provides further evidence
      for the anti-inflammatory properties of Ag-PVP nanoparticles, and opens new
      possibilities for smaller sizes of Ag-PVP nanoparticles to be employed as
      regulators of inflammatory responses induced by C. trachomatis. 

PMID- 23882140
TI  - Novel preparation method for sustained-release PLGA microspheres using water-in
      oil-in-hydrophilic-oil-in-water emulsion.
AB  - An increasing number of drugs are needing improved formulations to optimize
      patient compliance because of their short half-lives in blood. Sustained-release
      formulations of drugs are often required for long-term efficacy, and microspheres
      are among the most popular ones. When drugs are encapsulated into microsphere
      formulations, different methods of preparation need to be used according to
      specific clinical requirements and the differing physicochemical characteristics
      of individual drugs. In this work, we developed a novel method for sustained
      release drug delivery using a water-in-oil-in-hydrophilic oil-in-water (w/o/oh/w)
      emulsion to encapsulate a drug into poly(lactic-co-glycolic acid) (PLGA)
      microspheres. Different effects were achieved by varying the proportions and
      concentrations of hydrophilic oil and PLGA. Scanning electron and optical
      microscopic images showed the surfaces of the microspheres to be smooth and that
      their morphology was spherical. Microspheres prepared using the w/o/oh/w emulsion
      were able to load protein efficiently and had sustained-release properties. These
      results indicate that the above-mentioned method might be useful for developing
      sustained-release microsphere formulations in the future. 

PMID- 23882141
TI  - Prevalence of metabolic syndrome and its association with depression in patients
      with schizophrenia.
AB  - PURPOSE: To identify the point prevalence of metabolic syndrome in patients with
      schizophrenia and to evaluate the association between depressive symptoms and
      metabolic syndrome in patients with schizophrenia. PATIENTS AND METHODS:
      Metabolic syndrome was assessed based on an updated definition derived from the
      modified National Cholesterol Education Program Adult Treatment Panel III (NCEP
      ATP III) and the International Diabetes Federation criteria. The 17-item Hamilton
      Depression Rating Scale (HDRS-17) was used to measure depressive symptoms in 80
      patients with schizophrenia. Odds ratios and 95% confidence intervals were
      calculated using logistic regression for the association between each depressive
      symptom and metabolic syndrome. RESULTS: The point prevalence rates of metabolic
      syndrome according to the modified NCEP-ATP III and International Diabetes
      Federation criteria were 37% and 35%, respectively. The risk of having metabolic
      syndrome significantly increased in those who were widowed or separated, or had
      longer duration of illness. Central obesity was the metabolic feature with the
      highest odds ratios for metabolic syndrome at 19.3. Three out of 17 items of HDRS
      subscales were found to be significantly associated with metabolic syndrome,
      including depressed mood, middle insomnia, and retardation with the odds ratios
      of 3.0, 3.4, and 3.6, respectively. CONCLUSION: This study showed that the
      prevalence of metabolic syndrome in patients with schizophrenia was higher than
      the overall rate but was slightly lower than in the general population in the
      USA. Central obesity, measured by waist circumference, was found to be highly
      correlated with metabolic syndrome. Depressed mood, middle insomnia, and
      retardation were significantly associated with metabolic syndrome in patients
      with schizophrenia. Waist circumference and screening for depression should be
      done at the clinics during patient follow-up.

PMID- 23882142
TI  - Apraxia for differentiating Alzheimer's disease from subcortical vascular
      dementia and mild cognitive impairment.
AB  - Although ideomotor limb apraxia is considered to be a typical sign of cortical
      pathologies such as Alzheimer's disease (AD), it has been also reported in
      subcortical neurodegenerative diseases and vascular lesions. We aimed to
      investigate the difference between AD, subcortical vascular dementia (SVaD) and
      mild cognitive impairment (MCI) patients by means of ideomotor limb apraxia
      frequency and severity. Ninety-six AD, 72 SVaD, and 84 MCI patients were assessed
      with the mini-mental status examination (MMSe), clinical dementia rating (CDR)
      and the apraxia screening test of TULIA (AST). Apraxia was significantly more
      frequent in the AD patients (32.3%) than in both of the SVaD (16.7%) and MCI
      (4.8%) patients. The frequency of apraxia was also significantly higher in SVaD
      patients than in MCI patients. AD patients had significantly lower apraxia scores
      than both SVaD and MCI patients. In addition, a significant difference was found
      between SVaD and MCI patients in terms of apraxia scores. These results suggest
      that the widespread belief of the association between apraxia and cortical
      dementias is not exactly correct. The significant difference between both of the
      dementia groups and the MCI patients suggests that the absence of apraxia can be
      an indicator for MCI diagnosis. 

PMID- 23882143
TI  - Hemodynamic and hematologic profile of healthy adults ingesting dietary
      supplements containing 1,3-dimethylamylamine and caffeine.
AB  - BACKGROUND: 1,3-dimethylamylamine (a constituent of geranium), alone and in
      combination with caffeine, is widely used within dietary supplements. We have
      recently determined the hemodynamic effects of 1,3-dimethylamylamine and caffeine
      alone and in combination, using a single ingestion study. However, no study has
      determined the hemodynamic effects of these ingredients following chronic use.
      Moreover, no study has determined the effects of these ingredients on bloodborne
      variables related to health and safety. Therefore, the purpose of this
      investigation was to assess the hemodynamic and hematologic profile of two
      different dietary supplements containing 1,3-dimethylamylamine and caffeine (in
      addition to other ingredients), before and after two weeks of daily intake.
      METHODS: 7 men (24.9 +/- 4.2 yrs) ingested the dietary supplement Jack3dTM, while
      4 men and 2 women (22.5 +/- 1.8 yrs) ingested the dietary supplement OxyELITE
      ProTM once per day for two weeks. On days 1 and 15, resting heart rate (HR),
      systolic (SBP), and diastolic (DBP) blood pressure were measured and rate
      pressure product (RPP) was calculated. Fasting blood samples were analyzed for
      complete blood counts, comprehensive metabolic panel, and lipid panel. These
      tests were done prior to ingestion of supplement. On days 1 and 15 following
      blood collection, subjects ingested the assigned supplement (2 servings) and HR,
      SBP, DBP, and RPP were recorded at 30, 60, 90, and 120 minutes post-ingestion.
      RESULTS: After 14 days of treatment, resting HR, SBP, DBP, and RPP were not
      increased (P > 0.05). No significant changes were noted in any measured
      bloodborne variable, with the exception of an increase in fasting blood glucose
      with ingestion of Jack3dTM (P = 0.02). In response to acute intake of the
      supplements, HR, DBP, and RPP were not increased statistically (P > 0.05). SBP
      was increased with OxyELITE ProTM (P = 0.03), but not with Jack3dTM (P = 0.09).
      Compared to pre-ingestion and in general, both supplements resulted in an
      increase in SBP, DBP, and RPP from 5%-15%, with a peak occurring at the 60 or 90
      minute post-ingestion time. CONCLUSION: Acute ingestion of OxyELITE ProTM, but
      not Jack3dTM, results in an increase in SBP. Chronic intake of two servings per
      day of OxyELITE ProTM or Jack3dTM over a 14 day period does not result in an
      elevation in resting HR, SBP, DBP, or RPP. No significant changes are noted in
      any measured bloodborne variable following 14 days of ingestion, with the
      exception of blood glucose with Jack3dTM. Longer term intervention studies
      inclusive of larger sample sizes are needed to extend these findings.

PMID- 23882144
TI  - Biochemical and anthropometric effects of a weight loss dietary supplement in
      healthy men and women.
AB  - BACKGROUND: We have recently noted an acute increase in circulating free fatty
      acids and glycerol, as well as resting metabolic rate, when men and women
      ingested the dietary supplement OxyELITE ProTM in a single dose. We have also
      noted a reduction in appetite when subjects were treated with this supplement for
      14 consecutive days. It is possible that such findings may favor body weight and
      fat loss over time. Therefore, the purpose of the present study was to determine
      the effects of this dietary supplement on weight loss and associated markers
      using an eight week intervention. METHODS: Exercise-trained subjects were
      randomly assigned in double blind manner to ingest either the dietary supplement
      (n = 16; aged 22.8 +/- 0.7) or a placebo (n = 16; 22.5 +/- 0.5) every day for
      eight weeks. Body weight, body composition, skinfold thickness, serum lipids, and
      appetite were measured as the primary outcome variables. As measures of
      supplement safety, a complete blood count and comprehensive metabolic panel were
      performed, and resting heart rate and blood pressure were measured (pre and post
      intervention). RESULTS: No interactions or main effects were noted for our
      primary outcome measures (P > 0.05). However, when comparing pre and post
      intervention values for the supplement, significant decreases were noted in
      appetite, body weight, body fat percentage, and skinfold thickness (P < 0.05),
      while increases were noted for total and HDL-C, as well as for resting heart rate
      (P < 0.05). No changes were noted for placebo from pre to post intervention (P >
      0.05), with the exception of an increase in HDL-C (P < 0.05). Blood pressure and
      bloodborne safety variables were not differently impacted by supplement or
      placebo (P > 0.05), with the exception of monocytes, for which an interaction
      effect was noted (P = 0.04). CONCLUSION: These data indicate that the dietary
      supplement OxyELITE ProTM may assist in weight and body fat loss in a sample of
      exercise-trained men and women. The supplement does not result in any adverse
      effects pertaining to resting blood pressure or bloodborne markers of safety;
      however a small increase in resting heart rate is observed.

PMID- 23882145
TI  - A finished dietary supplement stimulates lipolysis and metabolic rate in young
      men and women.
AB  - BACKGROUND: Dietary supplements are often marketed to increase lipolysis and
      thermogenesis, with the proposed end result being weight loss and body fat
      reduction. It was the purpose of the present investigation to study the acute
      effects of a weight/fat loss supplement within a sample of healthy human
      subjects. METHODS: Twelve subjects (men 24.8 +/- 4.3 yrs; women 22.8 +/- 0.4 yrs)
      ingested a dietary supplement (OxyELITE ProTM) or a placebo, on two separate days
      in a double-blind, cross-over design. Blood samples were collected immediately
      before ingestion, and at 60 and 120 minutes post ingestion, and analyzed for
      plasma glycerol and free fatty acids (FFA). Breath samples were collected
      immediately before ingestion and at 30, 60, 90, and 120 minutes post ingestion,
      for a measure of kilocalorie expenditure using indirect calorimetry. Area under
      the curve (AUC) was calculated. Heart rate and blood pressure were recorded at
      all times and rate pressure product (RPP) was calculated. RESULTS: AUC was
      greater for supplement compared to placebo for glycerol (22.74 +/- 1.98 MUg . mL(
      1) . 2 hr(-1) vs. 15.76 +/- 1.36 MUg . mL(-1) . 2 hr(-1); P = 0.001), FFA (1.62
      +/- 0.07 mmol . L(-1) . 2 hr(-1) vs. 0.78 +/- 0.12 mmol . L(-1) . 2 hr(-1); P <
      0.0001), and kilocalorie expenditure (149 +/- 7 kcal . 2 hr(-1) vs. 122 +/- 8
      kcal . 2 hr(-1); P = 0.005). Heart rate (P = 0.02), systolic blood pressure (P <
      0.0001), and RPP (P = 0.002) were higher for supplement compared to placebo.
      CONCLUSION: Ingestion of OxyELITE ProTM resulted in an increase in blood markers
      of lipolysis, as well as metabolic rate, during a two-hour post ingestion time
      period. An increase in hemodynamic variables was also observed. These findings
      are in reference to a sample of healthy men and women who were naive to treatment
      with the dietary supplement. Additional work is needed to determine if the acute
      changes observed here would persist with chronic use of the supplement and
      possibly lead to weight/body fat loss over time.

PMID- 23882146
TI  - Impact of a dietary supplement containing 1,3-dimethylamylamine on blood pressure
      and bloodborne markers of health: a 10-week intervention study.
AB  - BACKGROUND: 1,3-dimethylamylamine is a commonly used ingredient within dietary
      supplements. Our prior work with this agent indicates a transient increase in
      blood pressure (systolic in particular) following oral ingestion of a single
      dosage, but no significant increase in resting blood pressure following chronic
      ingestion. Moreover, intervention studies involving both two and eight weeks of
      treatment with finished products containing 1,3-dimethylamylamine indicate
      minimal or no change in bloodborne markers of health. The present study sought to
      extend these findings by using a 10-week intervention trial to determine the
      change in selected markers of health in a sample of men. METHODS: 25 healthy men
      were randomly assigned to either a placebo (n = 13) or to a supplement containing
      1,3-dimethylamylamine (n = 12) for a period of 10 weeks. Before and after the
      intervention, resting blood pressure and heart rate were measured, and blood
      samples were collected for determination of complete blood count, metabolic
      panel, and lipid panel. RESULTS: No significant differences were noted between
      conditions for blood pressure (P > 0.05), although systolic blood pressure
      increased approximately 6 mmHg with the supplement (diastolic blood pressure
      decreased approximately 4 mmHg). A main effect for time was noted for heart rate
      (P = 0.016), with values decreasing from pre to post intervention. There were
      significant main effects for time for creatinine (increased from pre to post
      intervention; P = 0.043) and alkaline phosphatase (decreased from pre to post
      intervention; P = 0.009), with no condition differences noted (P > 0.05). There
      was a significant interaction noted for low density lipoprotein cholesterol (LDL
      C) (P = 0.043), with values decreasing in the supplement group from pre to post
      intervention approximately 7 mg . dL(-1) (P = 0.034). No other effects of
      significance were noted for bloodborne variables. CONCLUSION: These data indicate
      that a dietary supplement containing 1,3-dimethylamylamine does not result in a
      statistically significant increase in resting heart rate or blood pressure
      (although systolic blood pressure is increased ~6 mmHg with supplement use). The
      supplement does not negatively impact bloodborne markers of health. Further study
      is needed involving a longer intervention period, a larger sample size, and
      additional measures of health and safety.

PMID- 23882147
TI  - Plasma copper and zinc concentration in individuals with autism correlate with
      selected symptom severity.
AB  - AIM: To assess plasma zinc and copper concentration in individuals with autism
      and correlate these levels with symptom severity. SUBJECTS AND METHODS: Plasma
      from 102 autistic individuals, and 18 neurotypical controls, were tested for
      plasma zinc and copper using inductively-coupled plasma-mass spectrometry. Copper
      and zinc levels and Cu/Zn were analyzed for possible correlation with severity of
      19 symptoms. RESULTS: Autistic individuals had elevated plasma levels of copper
      and Cu/Zn and lower, but not significantly lower, plasma Zn compared to
      neurotypical controls. There was a correlation between Cu/Zn and expressive
      language, receptive language, focus attention, hyperactivity, fine motor skills,
      gross motor skills and Tip Toeing. There was a negative correlation between
      plasma zinc concentration and hyperactivity, and fine motor skills severity.
      DISCUSSION: These results suggest an association between plasma Cu/Zn and
      severity of symptoms associated with autism.

PMID- 23882148
TI  - Adding diet and exercise counseling to the health promotion plan alleviates
      anthropometric and metabolic complications in patients with metabolic syndrome.
AB  - We investigated the effects of individual (IC) and group (GC) diet and exercise
      counseling in men with metabolic syndrome. Participants received exercise
      instruction and exercise load was monitored. IC participants received individual
      diet counseling sessions and general consultations at baseline and monthly. GC
      participants received a group diet counseling session at baseline and general
      consultations at baseline and monthly. In the IC group, body mass index (BMI)
      percent body fat, waist circumference, diastolic blood pressure, low-density
      lipoprotein cholesterol, glycosylated hemoglobin A1c, and liver function levels
      were reduced significantly after 3 months, whereas in the GC group, waist
      circumference and levels of liver function were reduced. Exercise load was
      negatively correlated with change in BMI and waist circumference in the IC group,
      and positively correlated with changes in high-density lipoprotein cholesterol
      levels in all subjects and in the GC group. Diet and exercise counseling,
      especially IC, may benefit patients with metabolic syndrome. 

PMID- 23882149
TI  - Effects of caffeine on metabolism and mitochondria biogenesis in rhabdomyosarcoma
      cells compared with 2,4-dinitrophenol.
AB  - PURPOSE: This work investigated if treatment with caffeine or 2,4-dinitrophenol
      (DNP) induce expression of peroxisome proliferator-activated receptor coactivator
      1 alpha (PGC-1alpha) and increase both mitochondrial biosynthesis and metabolism
      in skeletal muscle. METHODS: Human rhabdomyosarcoma cells were treated with
      either ethanol control (0.1% final concentration) caffeine, or DNP at 250 or 500
      MUM for 16 or 24 hours. PGC-1alpha RNA levels were determined using quantitative
      reverse transcriptase polymerase chain reaction (qRT-PCR). PGC-1alpha protein and
      mitochondrial content was determined using flow cytometry and
      immunohistochemistry. Metabolism was determined by quantification of
      extracellular acidification rate and oxygen consumption rate. RESULTS: Treatment
      with either caffeine or DNP induced PGC-1alpha RNA and protein as well as
      mitochondrial content compared with control. Treatment with caffeine and DNP also
      significantly increased oxidative metabolism and total metabolic rate compared
      with control. Caffeine similarly increased metabolism and mitochondrial content
      compared with DNP. CONCLUSION: This work identified that both caffeine and DNP
      significantly induce PGC-1alpha, and increase both metabolism and mitochondrial
      content in skeletal muscle.

PMID- 23882150
TI  - Low educational status, smoking, and multidisciplinary team experience predict
      hospital length of stay after bariatric surgery.
AB  - OBJECTIVE: The objective of the present study was to identify new risk factors
      associated with longer hospitalization following bariatric surgery. METHODS:
      Patient clinical, social, and biochemical data in addition to multidisciplinary
      team experience were analyzed in a cohort that included all patients undergoing
      bariatric surgery at our hospital. The primary outcome was length of hospital
      stay (LOS). Mortality was recorded to validate the obesity surgery mortality risk
      score (OS-MRS). RESULTS: This study included 299 sequential patients, 41 +/- 10
      years of age, and BMI of 50 +/- 8 kg/m(2) who underwent bariatric surgery. Two
      thirds (196) of patients were hypertensive, a third (86) were diabetic and a
      third (91) were current or former smokers. Overall, LOS was 8 +/- 5 days. The
      predictors of a longer LOS were smoking (P < 0.05) and less multidisciplinary
      team experience (P < 0.05). Looking at only the last three years of data, LOS was
      6 +/- 5 days, and the predictors of a longer LOS were low educational attainment
      (P < 0.02) and smoking (P < 0.01) but not team experience. The global mortality
      was 2.6%, with the OS-MRS identifying a high-risk group. CONCLUSION: Excluding
      the initial learning phase, longer LOS independent predictors were patient low
      educational attainment and smoking. These predictors can help guide care to
      reduce complications.

PMID- 23882151
TI  - The Effects of Cinnamomum Cassia on Blood Glucose Values are Greater than those
      of Dietary Changes Alone.
AB  - Eighteen type II diabetics (9 women and 9 men) participated in a 12-week trial
      that consisted of 2 parts, a 3-week control phase followed by a 9-week
      experimental phase where half of the subjects received 1000 mg of Cinnamomum
      cassia while the other half received 1000 mg of a placebo pill. All of the
      subjects that were in the cinnamon group had a statistically significant decrease
      in their blood sugar levels with a P-value of 3.915 * 10(-10). The subjects in
      the cinnamon group had an average overall decrease in their blood sugar levels of
      about 30 mg/dL, which is comparable to oral medications available for diabetes.
      All subjects were educated on appropriate diabetic diets and maintained that diet
      for the entire 12 week study. Greater decreases in blood glucose values were
      observed in patients using the cinnamon compared to those using the dietary
      changes alone. 

PMID- 23882152
TI  - Cost-effectiveness of zofenopril in patients with left ventricular systolic
      dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4.
AB  - BACKGROUND: In SMILE-4 (the Survival of Myocardial Infarction Long-term
      Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to
      ramipril + ASA in reducing the occurrence of major cardiovascular events in
      patients with left ventricular dysfunction following acute myocardial infarction.
      The present post hoc analysis was performed to compare the cost-effectiveness of
      zofenopril and ramipril. METHODS: In total, 771 patients with left ventricular
      dysfunction and acute myocardial infarction were randomized in a double-blind
      manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382)
      + ASA 100 mg/day and were followed up for one year. The primary study endpoint
      was the one-year combined occurrence of death or hospitalization for
      cardiovascular causes. The economic analysis was based on evaluation of cost of
      medications and hospitalizations and was applied to the intention-to-treat
      population (n = 716). Cost data were drawn from the National Health Service
      databases of the European countries participating in the study. The incremental
      cost-effectiveness ratio was used to quantify the cost per event prevented with
      zofenopril versus ramipril. RESULTS: Zofenopril significantly (P = 0.028) reduced
      the risk of the primary study endpoint by 30% as compared with ramipril (95%
      confidence interval, 4%-49%). The number needed to treat to prevent a major
      cardiovascular event with zofenopril was 13 less than with ramipril. The cost of
      drug therapies was higher with zofenopril (328.78 Euros per patient per year, n =
      365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost
      related to the occurrence of major cardiovascular events requiring
      hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for
      ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril
      was 2125.45 Euros per event prevented (worst and best case scenario in the
      sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). CONCLUSION:
      Zofenopril is a viable and cost-effective treatment for managing patients with
      left ventricular dysfunction after acute myocardial infarction.

PMID- 23882153
TI  - Cost-effectiveness of bazedoxifene versus raloxifene in the treatment of
      postmenopausal women in Spain.
AB  - BACKGROUND: The purpose of this study was to assess the cost-effectiveness of
      bazedoxifene and raloxifene for prevention of vertebral and nonvertebral
      fractures among postmenopausal Spanish women aged 55-82 years with established
      osteoporosis and a high fracture risk. METHODS: A Markov model was developed to
      represent the transition of a cohort of postmenopausal osteoporotic women through
      different health states, ie, patients free of fractures, patients with vertebral
      or nonvertebral fractures, and patients recovered from a fracture. Efficacy data
      for bazedoxifene were obtained from the Osteoporosis Study. The perspective of
      the Spanish National Health Service was chosen with a time horizon of 27 years.
      Costs were reported in 2010 Euros. Deterministic results were presented as
      expected cost per quality-adjusted life-year (QALY), and probabilistic results
      were represented in cost-effectiveness planes. RESULTS: In deterministic
      analysis, the expected cost per patient was higher in the raloxifene cohort
      (?13,881) than in the bazedoxifene cohort (?13,436). QALYs gained were slightly
      higher in the bazedoxifene cohort (14.56 versus 14.54). Results from
      probabilistic sensitivity analysis showed that bazedoxifene has a slightly higher
      probability of being cost-effective for all threshold values independent of the
      maximum that the National Health Service is willing to pay per additional QALY.
      CONCLUSION: Bazedoxifene was shown to be a cost-effective treatment option for
      the prevention of fractures in Spanish women with postmenopausal osteoporosis and
      a high fracture risk. When comparing bazedoxifene with raloxifene, it may be
      concluded that the former is the dominant strategy.

PMID- 23882154
TI  - Genetic basis of cohesinopathies.
AB  - Cohesin is a ring-form multifunctional protein complex, which was discovered
      during a search for molecules that keep sister chromatids together during
      segregation of chromosomes during cell division. In the past decade, a large
      number of results have also demonstrated a need for the cohesin complex in other
      crucial events in the life cycle of the cell, including DNA duplication,
      heterochromatin formation, DNA double-strand break repair, and control of gene
      expression. The dynamics of the cohesin ring are modulated by a number of
      accessory and regulatory proteins, known as cohesin cofactors. Loss of function
      of the cohesin complex is incompatible with life; however, mutations in the genes
      encoding for cohesin subunits and/or cohesin cofactors, which have very little or
      a null effect on chromosome segregation, represent a newly recognized class of
      human genetic disorders known as cohesinopathies. A number of genetic,
      biochemical, and clinical approaches, and importantly, animal models, can help us
      to determine the underlying mechanisms for these human diseases. 

PMID- 23882155
TI  - Incidence of and risk factors for hungry bone syndrome in 84 patients with
      secondary hyperparathyroidism.
AB  - INTRODUCTION: Secondary hyperparathyroidism develops in nearly all patients with
      end-stage renal disease. Parathyroidectomy is often performed when medical
      therapy fails. The most common postoperative complication, hungry bone syndrome
      (HBS), requires early recognition and treatment. MATERIALS AND METHODS: A total
      of 84 patients who underwent parathyroidectomy because of secondary
      hyperparathyroidism were investigated. Detailed analysis of laboratory parameters
      (calcium, phosphate, parathyroid hormone, hemoglobin, and urea levels) and
      baseline characteristics (age at time of surgery, duration of renal replacement
      therapy, and medication) was performed to detect preoperative predictors for the
      development of HBS. RESULTS: Average overall follow-up of the cohort was 4.7
      years. Within this time frame, 13 of 84 patients had to undergo a second surgery
      because of recurrent disease, and HBS occurred in 51.2%. Only decreased
      preoperative calcium levels and younger age at time of surgery were significant
      predictors of HBS. Minimal levels of calcium were detected 3 weeks after surgery.
      Preoperative vitamin D therapy could not prevent HBS and could not shorten the
      duration of intravenous calcium supplementation. CONCLUSION: HBS is a very common
      complication after parathyroidectomy. Younger patients and patients with low
      preoperative calcium levels were at higher risk for the development of HBS.
      Remarkably, preoperative vitamin D therapy could not prevent HBS and had no
      impact on the length of intravenous calcium supplementation. Intensive monitoring
      of calcium levels must be performed for at least 3 weeks after surgery.

PMID- 23882156
TI  - Beta-blockers: friend or foe in asthma?
AB  - BACKGROUND AND AIM: Recently, beta-blockers have been suggested as a potential
      maintenance treatment option for asthma. The aim of this review is to provide an
      overview of the current knowledge of the potential benefits and risks of beta
      blocker therapy for asthma. METHOD: Systematic literature review. RESULTS: No
      significant increase in the number of patients requiring rescue oral
      corticosteroid for an exacerbation of asthma has been observed after initiation
      of beta-blocker treatment. Patients with mild to moderate reactive airway
      disease, probably both asthma and chronic obstructive pulmonary disease, may have
      a limited fall in forced expiratory volume in 1 second (FEV1) following single
      dose administration of beta-blocker, whereas no change in FEV1 has been reported
      following long-term administration. In a murine model of asthma, long-term
      administration of beta-blockers resulted in a decrease in airway
      hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with
      this, long-term administration of a nonselective beta-blocker to steroid-naive
      asthma patients has shown a dose-dependent improvement in airway
      hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant
      change in FEV1. Furthermore, available studies show that bronchoconstriction
      induced by inhaled methacholine is reversed by salbutamol in patients on regular
      therapy with a beta-blocker. On the other hand, a recent placebo-controlled trial
      of propranolol and tiotropium bromide added to inhaled corticosteroids revealed
      no effect on airway hyperresponsiveness and a small, not statistically
      significant, fall in FEV1 in patients classified as having mild to moderate
      asthma. CONCLUSION: The available, although limited, evidence suggests that a
      dose-escalating model of beta-blocker therapy to patients with asthma is well
      tolerated, does not induce acute bronchoconstriction, and, not least, may have
      beneficial effects on airway inflammation and airway hyperresponsiveness in some
      patients with asthma. Further studies addressing the potential role of beta
      blocker therapy for asthma are clearly needed, but careful selection of the
      target population is warranted.

PMID- 23882157
TI  - NY-ESO-1-specific immunological pressure and escape in a patient with metastatic
      melanoma.
AB  - During cancer progression, malignant cells may evade immunosurveillance. However,
      evidence for immunological escape in humans is scarce. We report here the
      clinical course of a melanoma patient whose initial tumor was positive for the
      antigens NY-ESO-1, MAGE-C1, and Melan-A. Upon immunization with a recombinant
      vaccinia/fowlpox NY-ESO-1 construct, the patient experienced a mixed clinical
      response and spreading of the NY-ESO-1 epitopes in the CD4+ T cell compartment.
      After NY-ESO-1 protein + CpG immunization, the patient's anti-NY-ESO-1 IgG
      response increased. Over the following years, progressing lesions were resected
      and found to be NY-ESO-1-negative while being positive for MAGE-C1, Melan-A, and
      MHC-I. The fatal, inoperable brain metastasis was analyzed after his death and
      also proved to be NY-ESO-1-negative, while being positive for MAGE-C1 and Melan
      A, as well as MHC-I. We propose that cancer control and cancer escape in this
      patient were governed by NY-ESO-1-specific immunological pressure. Our findings
      provide evidence for the existence of immunoediting and immunoescape in this
      cancer patient. 

PMID- 23882158
TI  - Structured reporting of T cell assay results.

PMID- 23882159
TI  - Human ovarian tumor ascites fluids rapidly and reversibly inhibit T cell receptor
      induced NF-kappaB and NFAT signaling in tumor-associated T cells.
AB  - Human memory T cells present in ovarian tumor ascites fluids fail to respond
      normally to stimulation via the T cell receptor (TCR). This immunosuppression is
      manifested by decreases in NF-kappaB and NFAT activation, IFN-gamma production,
      and cell proliferation in response to TCR stimulation with immobilized antibodies
      to CD3 and CD28. The anergy of the tumor-associated T cells (TATs) is mediated by
      soluble factors present in ovarian tumor ascites fluids. The non-responsiveness
      of the T cells is quickly reversed when the cells are assayed in the absence of
      the ascites fluid, and is rapidly reestablished when a cell-free ascites fluid is
      added back to the T cells. Based upon the observed normal phosphorylation
      patterns of the TCR proximal signaling molecules, the inhibition of NF-kappaB,
      and NFAT activation in response to TCR stimulation, as well as the ability of the
      diacylglycerol analog PMA and the ionophore ionomycin to bypass the ascites fluid
      induced TCR signaling arrest, the site of the arrest in the activation cascade
      appears to be at or just upstream of PLC-gamma. An identical TCR signaling arrest
      pattern was observed when T cells derived from normal donor peripheral blood were
      incubated with either malignant or nonmalignant (cirrhotic) ascites fluids. The
      immunosuppressive activity of ascites fluids reported here suggests that soluble
      factors acting directly or indirectly upon T cells present within tumors
      contribute to the anergy that has previously been observed in T cells derived
      from malignant and nonmalignant inflammatory microenvironments. The soluble
      immunosuppressive factors represent potential therapeutic targets for ovarian
      cancer. 

PMID- 23882160
TI  - Database of T cell-defined human tumor antigens: the 2013 update.
AB  - The plethora of tumor antigens that have been--and are still being--defined
      required systematization to provide a comprehensive overview of those tumor
      antigens that are the most relevant targets for cancer immunotherapy approaches.
      Here, we provide a new update of a peptide database resource that we initiated
      many years ago. This database compiles all human antigenic peptides described in
      the literature that fulfill a set of strict criteria needed to ascertain their
      actual "tumor antigen" nature, as we aim at guiding scientists and clinicians
      searching for appropriate cancer vaccine candidates
      (www.cancerimmunity.org/peptide). In this review, we revisit those criteria in
      light of recent findings related to antigen processing. We also introduce the 29
      new tumor antigens that were selected for this 2013 update. Two of the new
      peptides show unusual features, which will be briefly discussed. The database now
      comprises a total of 403 tumor antigenic peptides.

PMID- 23882161
TI  - An analogue peptide from the Cancer/Testis antigen PASD1 induces CD8+ T cell
      responses against naturally processed peptide.
AB  - We have previously identified the novel Cancer/Testis antigen PASD1 by
      immunoscreening a testis library with pooled acute myeloid leukemia (AML) patient
      sera. To develop a cytotoxic T lymphocyte (CTL)-inducing vaccine, we have now
      investigated the carboxy-terminal region, known to contain serological
      determinants, for MHC class I (HLA-A?0201)-binding peptides. Algorithm-selected
      natural peptides failed to show detectable HLA-A?0201 binding in T2 assays.
      However, anchor-modified analogue peptides showed enhanced binding, with
      decreased off-rates. Analogue peptide-loaded antigen-presenting cells (APCs)
      induced IFN-gamma production by T cells from normal donors and patients. In
      addition, peptide-specific T cells could be expanded from cancer patients by
      stimulation with the PASD1 analogue peptide Pa14. For clinical application, a DNA
      fusion gene vaccine encoding Pa14 was designed and tested in "humanized" mice.
      Splenocytes from vaccinated mice showed in vitro cytotoxicity against tumour
      cells, either exogenously loaded with the corresponding wild-type peptide (Pw8)
      or expressing endogenously processed PASD1 protein. We show for the first time
      that a DNA vaccine encoding an altered PASD1 epitope can induce CTLs to target
      the natural peptide expressed by human tumour cells. 

PMID- 23882162
TI  - Advances in the treatment of visual hallucinations in neurodegenerative diseases.
AB  - Treatment of visual hallucinations in neurodegenerative disorders is not well
      advanced. The complexity of underlying mechanisms presents a number of potential
      avenues for developing treatments, but also suggests that any single one may be
      of limited efficacy. Reducing medication, with the careful introduction of
      antidementia medication if needed, is the mainstay of current management.
      Antipsychotic medication leads to excessive morbidity and mortality and should
      only be used in cases of high distress that do not otherwise respond. Education,
      reduction of risk factors and psychological treatments have limited evidence of
      efficacy, but are unlikely to cause harm.

PMID- 23882163
TI  - Multidisciplinary integrated Parent and Child Centres in Amsterdam: a qualitative
      study.
AB  - BACKGROUND: In several countries centres for the integrated delivery of services
      to the parent and child have been established. In the Netherlands family health
      care service centres, called Parent and Child Centres (PCCs) involve
      multidisciplinary teams. Here doctors, nurses, midwives, maternity help
      professionals and educationists are integrated into multidisciplinary teams in
      neighbourhood-based centres. To date there has been little research on the
      implementation of service delivery in these centres. STUDY DESIGN: A SWOT
      analysis was performed by use of triangulation data; this took place by
      integrating all relevant published documents on the origin and organization of
      the PCCs and the results from interviews with PCC experts and with PCC
      professionals (n=91). Structured interviews were performed with PCC-professionals
      [health care professionals (n=67) and PCC managers n=12)] and PCC-experts (n=12)
      in Amsterdam and qualitatively analysed thematically. The interview themes were
      based on a pre-set list of codes, derived from a prior documentation study and a
      focus group with PCC experts. RESULTS: Perceived advantages of PCCs were more
      continuity of care, shorter communication lines, low-threshold contact between
      professionals and promising future perspectives. Perceived challenges included
      the absence of uniform multidisciplinary guidelines, delays in communication with
      hospitals and midwives, inappropriate accommodation for effective professional
      integration, differing expectations regarding the PCC-manager role among PCC
      partners and the danger of professionals' needs dominating clients' needs.
      CONCLUSIONS: Professionals perceive PCCs as a promising development in the
      integration of services. Remaining challenges involved improvements at the
      managerial and organizational level. Quantitative research into the improvements
      in quality of care and child health is recommended.

PMID- 23882164
TI  - Open pre-schools at integrated health services-A program theory.
AB  - INTRODUCTION: Family centres in Sweden are integrated services that reach all
      prospective parents and parents with children up to their sixth year, because of
      the co-location of the health service with the social service and the open pre
      school. The personnel on the multi-professional site work together to meet the
      needs of the target group. The article explores a program theory focused on the
      open pre-schools at family centres. METHOD: A multi-case design is used and the
      sample consists of open pre-schools at six family centres. The hypothesis is
      based on previous research and evaluation data. It guides the data collection
      which is collected and analysed stepwise. Both parents and personnel are
      interviewed individually and in groups at each centre. FINDINGS: The hypothesis
      was expanded to a program theory. The compliance of the professionals was the
      most significant element that explained why the open access service facilitated
      positive parenting. The professionals act in a compliant manner to meet the needs
      of the children and parents as well as in creating good conditions for social
      networking and learning amongst the parents. CONCLUSION: The compliance of the
      professionals in this program theory of open pre-schools at family centres can be
      a standard in integrated and open access services, whereas the organisation form
      can vary. The best way of increasing the number of integrative services is to
      support and encourage professionals that prefer to work in a compliant manner.

PMID- 23882165
TI  - Development of a questionnaire to assess interprofessional collaboration between
      two different care levels.
AB  - INTRODUCTION: This paper reports the development and validation of a
      questionnaire to assess collaboration between clinical professionals from two
      different care levels (primary and specialised care), according to the
      clinicians' own perceptions. This questionnaire has been elaborated to be used as
      part of the monitoring and evaluation process of the integrated care pilots in
      the public Basque Health Service. METHODS: THE PROCESS WAS CARRIED OUT IN FOUR
      PHASES: development of the first version of the questionnaire, validation of the
      content, pre-testing, and evaluation of its construct validity and homogeneity in
      a sample of doctors and nurses. This last phase involved confirmatory factor
      analysis, as well as the calculation of Cronbach's alpha and various correlation
      coefficients. RESULTS: The process demonstrated that the theoretical content of
      the questionnaire was appropriate, and also that its items were clear, relevant
      and intelligible. The fit indices for the confirmatory factor analysis were:
      chi(2) of 45.51 (p=0.089), RMSEA of 0.043, RMR of 0.046, GFI of 0.92 and CFI of
      0.99. DISCUSSION: The statistics indicate a good fit between the data and a
      conceptual two-factor structure, in which both personal relationships between
      professionals and characteristics of the organisational environment are
      understood to underlie interprofessional collaboration. CONCLUSION: The end
      product is a new instrument with good validity to assess the degree of
      interprofessional collaboration between clinicians working at two different
      levels of care.

PMID- 23882166
TI  - Development of integrated care pathways: toward a care management system to meet
      the needs of frail and disabled community-dwelling older people.
AB  - INTRODUCTION: The home care and services provided to older adults with the same
      needs are often inadequate and highly varied. Integrated care pathways (ICPs) can
      resolve these issues. The aim of this study was to develop the content of ICPs to
      follow-up frail and disabled community-dwelling older people. THEORY AND METHOD:
      A RIGOROUS PROCESS WAS APPLIED ACCORDING TO A SERIES OF STEPS: identification of
      desirable characteristics and a theoretical framework; review of evidence-based
      practices and current practices; and determination of ICPs by an
      interdisciplinary task team. RESULTS: ICPs are intended to prevent specific
      problems, maximize independence, and promote successful aging. They are organized
      according to a dynamic process: (1) needs assessment and assessment of
      risk/protection factors; (2) data-collection summary and goals identification;
      (3) planning of interventions from a client-centered view; (4) coordination,
      delivery, and follow-up; and (5) identification of variances, as well as review
      and adjustment of plans. CONCLUSION: Once computerized, these ICPs will
      facilitate the exchange of information as well as the clinical decision-making
      process with a perspective to adequately matching the needs of an individual
      person with resources that delay or slow the progression of frailty and
      disability. Once aggregated, the data will also support managers in organizing
      teamwork and follow-up for clients.

PMID- 23882167
TI  - Learning to walk before we run: what can medical education learn from the human
      body about integrated care.
AB  - True integration requires a shift in all levels of medical and allied health
      education; one that emphasizes team learning, practicing, and evaluating from the
      beginning of each students' educational experience whether that is as physician,
      nurse, psychologist, or any other health profession. Integration of healthcare
      services will not occur until medical education focuses, like the human body, on
      each system working inter-dependently and cohesively to maintain balance through
      continual change and adaptation. The human body develops and maintains
      homeostasis by a process of communication: true integrated care relies on learned
      interprofessionality and ensures shared responsibility and practice. 

PMID- 23882168
TI  - Integrated healthcare for chronically ill. Reflections on the gap between science
      and practice and how to bridge the gap.
AB  - Integrated care offers an opportunity to address healthcare efficiency and
      effectiveness concerns and is especially relevant for elderly patients with
      different chronic illnesses. In current care standards for chronic care focus is
      often on one disease. The chronic care model (CCM) is used as the basis of
      integrated care programs. It identifies essential components that encourage high
      quality chronic disease care, involving the community and health system and
      including self-management support, delivery system design, decision support, and
      clinical information systems. Improvements in those interrelated components can
      produce system reform in which informed, activated patients interact with
      prepared, proactive practice teams. There is however a lack of research evidence
      for the impact of the chronic care model as a full model. Integrated care
      programs have widely varying definitions and components and failure to recognize
      these variations leads to inappropriate conclusions about the effectiveness of
      these programs and to inappropriate application of research results. It seems
      important to carefully consider the type and amount of data that are collected
      within the disease management programs for several purposes, as well as the
      methods of data collection. Understanding and changing the behavior of complex
      dynamic chronic care system requires an appreciation of its key patterns,
      leverage points and constraints. A different theoretical framework, that embraces
      complexity, is required. Research should be design-based, context bound and
      address relationships among agents in order to provide solutions that address
      locally defined demands and circumstances. 

PMID- 23882169
TI  - Developing an active implementation model for a chronic disease management
      program.
AB  - BACKGROUND: Introduction and diffusion of new disease management programs in
      healthcare is usually slow, but active theory-driven implementation seems to
      outperform other implementation strategies. However, we have only scarce evidence
      on the feasibility and real effect of such strategies in complex primary care
      settings where municipalities, general practitioners and hospitals should work
      together. The Central Denmark Region recently implemented a disease management
      program for chronic obstructive pulmonary disease (COPD) which presented an
      opportunity to test an active implementation model against the usual
      implementation model. The aim of the present paper is to describe the development
      of an active implementation model using the Medical Research Council's model for
      complex interventions and the Chronic Care Model. METHODS: We used the Medical
      Research Council's five-stage model for developing complex interventions to
      design an implementation model for a disease management program for COPD. First,
      literature on implementing change in general practice was scrutinised and
      empirical knowledge was assessed for suitability. In phase I, the intervention
      was developed; and in phases II and III, it was tested in a block- and cluster
      randomised study. In phase IV, we evaluated the feasibility for others to use our
      active implementation model. RESULTS: The Chronic Care Model was identified as a
      model for designing efficient implementation elements. These elements were
      combined into a multifaceted intervention, and a timeline for the trial in a
      randomised study was decided upon in accordance with the five stages in the
      Medical Research Council's model; this was captured in a PaTPlot, which allowed
      us to focus on the structure and the timing of the intervention. The
      implementation strategies identified as efficient were use of the Breakthrough
      Series, academic detailing, provision of patient material and meetings between
      providers. The active implementation model was tested in a randomised trial
      (results reported elsewhere). CONCLUSION: The combination of the theoretical
      model for complex interventions and the Chronic Care Model and the chosen
      specific implementation strategies proved feasible for a practice-based active
      implementation model for a chronic-disease-management-program for COPD. Using the
      Medical Research Council's model added transparency to the design phase which
      further facilitated the process of implementing the program. TRIAL REGISTRATION:
      http://www.clinicaltrials.gov/(NCT01228708).

PMID- 23882170
TI  - "Just another fish in the pond": the transitional care experience of a hip
      fracture patient.
AB  - INTRODUCTION: Miscommunication and lack of coordination can compromise care
      quality and patient safety during transitions in care, especially for medically
      complex older adults. Little research has been done to investigate care
      transitions from the perspective of those receiving and providing care. METHODS:
      This study explored multiple care transitions for an elderly hip fracture
      patient, post-surgery. Interviews and observations were conducted with the
      patient, their family caregivers, and health care providers, at each point of
      transition between four different care settings. RESULTS: FOUR KEY THEMES WERE
      IDENTIFIED OVER THE PATIENTS CARE TRAJECTORY: 'Missing Crucial Coversations'
      Patient and family caregivers did not feel involved or informed about decisions
      in care; 'Who's Who'-Confusion about the role of health care providers; 'Ready or
      Not'-Not knowing what to expect or what is expected; and, 'Playing by the Rules'
      Health system policies and procedures hinder individualized care. CONCLUSION:
      Study findings point to the need for the health care system to engage patients
      and family caregivers more fully and consistently in the process of care
      transitions as well as the importance of understanding these processes from
      multiple perspectives. Recommendations for system integration are proposed with a
      focus on transitional care.

PMID- 23882171
TI  - An in-depth analysis of theoretical frameworks for the study of care
      coordination.
AB  - INTRODUCTION: Complex chronic conditions often require long-term care from
      various healthcare professionals. Thus, maintaining quality care requires care
      coordination. Concepts for the study of care coordination require clarification
      to develop, study and evaluate coordination strategies. In 2007, the Agency for
      Healthcare Research and Quality defined care coordination and proposed five
      theoretical frameworks for exploring care coordination. This study aimed to
      update current theoretical frameworks and clarify key concepts related to care
      coordination. METHODS: We performed a literature review to update existing
      theoretical frameworks. An in-depth analysis of these theoretical frameworks was
      conducted to formulate key concepts related to care coordination. RESULTS: Our
      literature review found seven previously unidentified theoretical frameworks for
      studying care coordination. The in-depth analysis identified fourteen key
      concepts that the theoretical frameworks addressed. These were 'external
      factors', 'structure', 'tasks characteristics', 'cultural factors', 'knowledge
      and technology', 'need for coordination', 'administrative operational processes',
      'exchange of information', 'goals', 'roles', 'quality of relationship', 'patient
      outcome', 'team outcome', and '(inter)organizational outcome'. CONCLUSION: These
      14 interrelated key concepts provide a base to develop or choose a framework for
      studying care coordination. The relational coordination theory and the multi
      level framework are interesting as these are the most comprehensive.

PMID- 23882172
TI  - The process flow and structure of an integrated stroke strategy.
AB  - INTRODUCTION: In the Canadian province of Alberta access and quality of stroke
      care were suboptimal, especially in remote areas. The government introduced the
      Alberta Provincial Stroke Strategy (APSS) in 2005, an integrated strategy to
      improve access to stroke care, quality and efficiency which utilizes telehealth.
      RESEARCH QUESTION: What is the process flow and the structure of the care
      pathways of the APSS? METHODOLOGY: Information for this article was obtained
      using documentation, archival APSS records, interviews with experts, direct
      observation and participant observation. RESULTS: The process flow is described.
      The APSS integrated evidence-based practice, multidisciplinary communication, and
      telestroke services. It includes regular quality evaluation and improvement.
      CONCLUSION: Access, efficiency and quality of care improved since the start of
      the APSS across many domains, through improvement of expertise and equipment in
      small hospitals, accessible consultation of stroke specialists using telestroke,
      enhancing preventive care, enhancing multidisciplinary collaboration, introducing
      uniform best practice protocols and bypass-protocols for the emergency medical
      services. DISCUSSION: The APSS overcame substantial obstacles to decrease
      discrepancies and to deliver integrated higher quality care. Telestroke has
      proven itself to be safe and feasible. The APSS works efficiently, which is in
      line to other projects worldwide, and is, based on limited results, cost
      effective. Further research on cost-effectiveness is necessary.

PMID- 23882173
TI  - Taking integrated care forward: the need for shared values.

PMID- 23882174
TI  - A simple solution for model comparison in bold imaging: the special case of
      reward prediction error and reward outcomes.
AB  - Conventional neuroimaging techniques provide information about condition-related
      changes of the BOLD (blood-oxygen-level dependent) signal, indicating only where
      and when the underlying cognitive processes occur. Recently, with the help of a
      new approach called "model-based" functional neuroimaging (fMRI), researchers are
      able to visualize changes in the internal variables of a time varying learning
      process, such as the reward prediction error or the predicted reward value of a
      conditional stimulus. However, despite being extremely beneficial to the imaging
      community in understanding the neural correlates of decision variables, a model
      based approach to brain imaging data is also methodologically challenging due to
      the multicollinearity problem in statistical analysis. There are multiple sources
      of multicollinearity in functional neuroimaging including investigations of
      closely related variables and/or experimental designs that do not account for
      this. The source of multicollinearity discussed in this paper occurs due to
      correlation between different subjective variables that are calculated very close
      in time. Here, we review methodological approaches to analyzing such data by
      discussing the special case of separating the reward prediction error signal from
      reward outcomes. 

PMID- 23882176
TI  - Perception of stochastically undersampled sound waveforms: a model of auditory
      deafferentation.
AB  - Auditory deafferentation, or permanent loss of auditory nerve afferent terminals,
      occurs after noise overexposure and aging and may accompany many forms of hearing
      loss. It could cause significant auditory impairment but is undetected by regular
      clinical tests and so its effects on perception are poorly understood. Here, we
      hypothesize and test a neural mechanism by which deafferentation could
      deteriorate perception. The basic idea is that the spike train produced by each
      auditory afferent resembles a stochastically digitized version of the sound
      waveform and that the quality of the waveform representation in the whole nerve
      depends on the number of aggregated spike trains or auditory afferents. We reason
      that because spikes occur stochastically in time with a higher probability for
      high- than for low-intensity sounds, more afferents would be required for the
      nerve to faithfully encode high-frequency or low-intensity waveform features than
      low-frequency or high-intensity features. Deafferentation would thus degrade the
      encoding of these features. We further reason that due to the stochastic nature
      of nerve firing, the degradation would be greater in noise than in quiet. This
      hypothesis is tested using a vocoder. Sounds were filtered through ten adjacent
      frequency bands. For the signal in each band, multiple stochastically subsampled
      copies were obtained to roughly mimic different stochastic representations of
      that signal conveyed by different auditory afferents innervating a given cochlear
      region. These copies were then aggregated to obtain an acoustic stimulus. Tone
      detection and speech identification tests were performed by young, normal-hearing
      listeners using different numbers of stochastic samplers per frequency band in
      the vocoder. Results support the hypothesis that stochastic undersampling of the
      sound waveform, inspired by deafferentation, impairs speech perception in noise
      more than in quiet, consistent with auditory aging effects. 

PMID- 23882175
TI  - Ghrelin and eating behavior: evidence and insights from genetically-modified
      mouse models.
AB  - Ghrelin is an octanoylated peptide hormone, produced by endocrine cells of the
      stomach, which acts in the brain to increase food intake and body weight. Our
      understanding of the mechanisms underlying ghrelin's effects on eating behaviors
      has been greatly improved by the generation and study of several genetically
      manipulated mouse models. These models include mice overexpressing ghrelin and
      also mice with genetic deletion of ghrelin, the ghrelin receptor [the growth
      hormone secretagogue receptor (GHSR)] or the enzyme that post-translationally
      modifies ghrelin [ghrelin O-acyltransferase (GOAT)]. In addition, a GHSR-null
      mouse model in which GHSR transcription is globally blocked but can be cell
      specifically reactivated in a Cre recombinase-mediated fashion has been
      generated. Here, we summarize findings obtained with these genetically
      manipulated mice, with the aim to highlight the significance of the ghrelin
      system in the regulation of both homeostatic and hedonic eating, including that
      occurring in the setting of chronic psychosocial stress. 

PMID- 23882177
TI  - Bidirectional modulation of infralimbic dopamine D1 and D2 receptor activity
      regulates flexible reward seeking.
AB  - The development of addictive behavior is marked by a loss of behavioral
      flexibility. In part, this is due to an increase in the ability of environmental
      stimuli to elicit responding and decreased importance of the action-outcome
      relationship in behavioral control. It has previously been demonstrated that both
      inactivation of and dopamine (DA) infusions in the infralimbic prefrontal cortex
      (PFC) can restore behavioral flexibility in paradigms measuring habitual reward
      seeking. Here, we investigated the mechanism by which cortical DA would act to
      enable goal-directed actions after the transition to habitual behavior has been
      established. Further, we extended this work to include a novel mouse model of
      compulsive-like behavior in which we assessed reward seeking despite the
      possibility of adverse consequences. Our data show that DA receptor D1 inhibition
      or D2 activation both promote the expression of a flexible responding after the
      development of habitual or compulsive-like behavior, and we suggest that the
      ability of DA infusions in the infralimbic PFC to restore sensitivity to changes
      in outcome value depends on activation of DA D2 receptors. 

PMID- 23882178
TI  - Characterization of the effects of oxytocin on fear recognition in patients with
      schizophrenia and in healthy controls.
AB  - Individuals who suffer from schizophrenia often show a marked deficit in
      recognition of emotional facial expressions, as part of broader impairment of
      social cognition. Research has shown that recognition of negative emotions,
      specifically fear recognition, is particularly impaired among patients with
      schizophrenia. Recently we reported that intranasal administration of OT (IN OT)
      increased the ability to correctly recognize fear in a group of healthy men. The
      aim of the current study was to examine the effects of IN OT administration on
      fear recognition among patients with schizophrenia. Based on previous research,
      we also sought to examine a possible selective effect of OT dependent on baseline
      performance, hypothesizing that IN OT would have a greater enhancement effect on
      less proficient individuals. It was thus hypothesized that patients will show
      more improvement in fear recognition following the administration of IN OT as
      compared to controls. Sixty six participants (31 schizophrenia patients, 35
      healthy controls) were enrolled in the current study. All participants received
      treatment of a single dose of 24 IU IN OT and an equivalent amount of placebo, 1
      week apart. The participants' ability to accurately recognize fear and happiness
      was evaluated using a face morphing task. Overall, as a group, both patients and
      healthy control participants were more accurate in recognizing fearful facial
      expressions, but not happy faces, following IN OT administration, as compared to
      their performance following placebo. IN OT did not differentially affect emotion
      recognition in patients and healthy controls. Yet, the results indicated a
      selective effect for IN OT, in which the hormone improves fear recognition only
      among individuals whose baseline performance was below the median, regardless of
      their psychiatric status. 

PMID- 23882179
TI  - Tools, methods, and applications for optophysiology in neuroscience.
AB  - The advent of optogenetics and genetically encoded photosensors has provided
      neuroscience researchers with a wealth of new tools and methods for examining and
      manipulating neuronal function in vivo. There exists now a wide range of
      experimentally validated protein tools capable of modifying cellular function,
      including light-gated ion channels, recombinant light-gated G protein-coupled
      receptors, and even neurotransmitter receptors modified with tethered photo
      switchable ligands. A large number of genetically encoded protein sensors have
      also been developed to optically track cellular activity in real time, including
      membrane-voltage-sensitive fluorophores and fluorescent calcium and pH
      indicators. The development of techniques for controlled expression of these
      proteins has also increased their utility by allowing the study of specific
      populations of cells. Additionally, recent advances in optics technology have
      enabled both activation and observation of target proteins with high
      spatiotemporal fidelity. In combination, these methods have great potential in
      the study of neural circuits and networks, behavior, animal models of disease, as
      well as in high-throughput ex vivo studies. This review collects some of these
      new tools and methods and surveys several current and future applications of the
      evolving field of optophysiology. 

PMID- 23882180
TI  - Activation of CRH receptor type 1 expressed on glutamatergic neurons increases
      excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion
      channels.
AB  - Corticotropin-releasing hormone (CRH) plays an important role in a substantial
      number of patients with stress-related mental disorders, such as anxiety
      disorders and depression. CRH has been shown to increase neuronal excitability in
      the hippocampus, but the underlying mechanisms are poorly understood. The effects
      of CRH on neuronal excitability were investigated in acute hippocampal brain
      slices. Population spikes (PS) and field excitatory postsynaptic potentials
      (fEPSP) were evoked by stimulating Schaffer-collaterals and recorded
      simultaneously from the somatic and dendritic region of CA1 pyramidal neurons.
      CRH was found to increase PS amplitudes (mean +/- Standard error of the mean;
      231.8 +/- 31.2% of control; n = 10) while neither affecting fEPSPs (104.3 +/-
      4.2%; n = 10) nor long-term potentiation (LTP). However, when Schaffer
      collaterals were excited via action potentials (APs) generated by stimulation of
      CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 +/- 3.6%; n = 8) and
      the magnitude of LTP in the CA1 region. Experiments in slices from transgenic
      mice revealed that the effect on PS amplitude is mediated exclusively by CRH
      receptor 1 (CRHR1) expressed on glutamatergic neurons. The effects of CRH on PS
      were dependent on phosphatase-2B, L- and T-type calcium channels and voltage
      gated potassium channels but independent on intracellular Ca(2+)-elevation. In
      patch-clamp experiments, CRH increased the frequency and decay times of APs and
      decreased currents through A-type and delayed-rectifier potassium channels. These
      results suggest that CRH does not affect synaptic transmission per se, but
      modulates voltage-gated ion currents important for the generation of APs and
      hence elevates by this route overall neuronal activity. 

PMID- 23882182
TI  - Contribution of apoptosis-associated signaling pathways to epileptogenesis:
      lessons from Bcl-2 family knockouts.
AB  - Neuronal cell death is a pathophysiological consequence of many brain insults
      that trigger epilepsy and has been implicated as a causal factor in
      epileptogenesis. Seizure-induced neuronal death features excitotoxic necrosis and
      apoptosis-associated signaling pathways, including activation of multiple members
      of the Bcl-2 gene family. The availability of mice in which individual Bcl-2
      family members have been deleted has provided the means to determine whether they
      have causal roles in neuronal death and epileptogenesis in vivo. Studies show
      that multiple members of the Bcl-2 family are activated following status
      epilepticus and the seizure and damage phenotypes of eight different knockouts of
      the Bcl-2 family have now been characterized. Loss of certain pro-apoptotic
      members, including Puma, protected against seizure-induced neuronal death whereas
      loss of anti-apoptotic Mcl-1 and Bcl-w enhanced hippocampal damage. Notably, loss
      of two putatively pro-apoptotic members, Bak and Bmf, resulted in more seizure
      damage while deletion of Bid had no effect, indicating the role of certain Bcl-2
      family proteins in epileptic brain injury is distinct from their contributions
      following other stressors or in non-CNS tissue. Notably, Puma-deficient mice
      develop fewer spontaneous seizures after status epilepticus suggesting
      neuroprotection may preserve functional inhibition, either directly by preserving
      neuronal networks or indirectly, for example by limiting reactive gliosis and pro
      inflammatory responses to neuronal death. Together, these studies support
      apoptosis-associated molecular mechanisms controlling neuronal death as a
      component of epileptogenesis which might be targetable to protect against seizure
      damage, cognitive deficits and mitigate the severity of syndrome following
      epilepsy-precipitating injuries to the brain. 

PMID- 23882181
TI  - Homeostatic control of brain function - new approaches to understand
      epileptogenesis.
AB  - Neuronal excitability of the brain and ongoing homeostasis depend not only on
      intrinsic neuronal properties, but also on external environmental factors;
      together these determine the functionality of neuronal networks. Homeostatic
      factors become critically important during epileptogenesis, a process that
      involves complex disruption of self-regulatory mechanisms. Here we focus on the
      bioenergetic homeostatic network regulator adenosine, a purine nucleoside whose
      availability is largely regulated by astrocytes. Endogenous adenosine modulates
      complex network function through multiple mechanisms including adenosine receptor
      mediated pathways, mitochondrial bioenergetics, and adenosine receptor
      independent changes to the epigenome. Accumulating evidence from our laboratories
      shows that disruption of adenosine homeostasis plays a major role in
      epileptogenesis. Conversely, we have found that reconstruction of adenosine's
      homeostatic functions provides new hope for the prevention of epileptogenesis. We
      will discuss how adenosine-based therapeutic approaches may interfere with
      epileptogenesis on an epigenetic level, and how dietary interventions can be used
      to restore network homeostasis in the brain. We conclude that reconstruction of
      homeostatic functions in the brain offers a new conceptual advance for the
      treatment of neurological conditions which goes far beyond current target-centric
      treatment approaches. 

PMID- 23882184
TI  - The spatial representations acquired in CA3 by self-organizing recurrent
      connections.
AB  - Neural computation models have hypothesized that the dentate gyrus (DG) drives
      the storage in the CA3 network of new memories including, e.g., in rodents,
      spatial memories. Can recurrent CA3 connections self-organize, during storage,
      and form what have been called continuous attractors, or charts-so that they
      express spatial information later, when aside from a partial cue the information
      may not be available in the inputs? We use a simplified mathematical network
      model to contrast the properties of spatial representations self-organized
      through simulated Hebbian plasticity with those of charts pre-wired in the
      synaptic matrix, a control case closer to the ideal notion of continuous
      attractors. Both models form granular quasi-attractors, characterized by drift,
      which approach continuous ones only in the limit of an infinitely large network.
      The two models are comparable in terms of precision, but not of accuracy: with
      self-organized connections, the metric of space remains distorted, ill-adequate
      for accurate path integration, even when scaled up to the real hippocampus. While
      prolonged self-organization makes charts somewhat more informative about position
      in the environment, some positional information is surprisingly present also
      about environments never learned, borrowed, as it were, from unrelated charts. In
      contrast, context discrimination decreases with more learning, as different
      charts tend to collapse onto each other. These observations challenge the
      feasibility of the idealized CA3 continuous chart concept, and are consistent
      with a CA3 specialization for episodic memory rather than path integration. 

PMID- 23882183
TI  - Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its
      relevance to schizophrenia.
AB  - Schizophrenia is a heterogeneous group of disorders with unknown etiology.
      Although abnormalities in multiple neurotransmitter systems have been linked to
      schizophrenia, alterations in dopamine (DA) neurotransmission remain central to
      the treatment of this disorder. Given that schizophrenia is considered a
      neurodevelopmental disorder we have hypothesized that abnormal DA signaling in
      the adult patient may result from altered DA signaling during fetal brain
      development. Environmental and genetic risk factors can be modeled in rodents to
      allow for the investigation of early neurodevelopmental pathogenesis that may
      lead to clues into the etiology of schizophrenia. To address this we created an
      animal model of one such risk factor, developmental vitamin D (DVD) deficiency.
      DVD-deficient adult rats display an altered behavioral profile in response to DA
      releasing and blocking agents that are reminiscent of that seen in schizophrenia
      patients. Furthermore, developmental studies revealed that DVD deficiency also
      altered cell proliferation, apoptosis, and neurotransmission across the embryonic
      brain. In particular, DVD deficiency reduces the expression of crucial
      dopaminergic specification factors and alters DA metabolism in the developing
      brain. We speculate such alterations in fetal brain development may change the
      trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed
      in adult offspring. The widespread evidence that both dopaminergic and structural
      changes are present in people who develop schizophrenia prior to onset also
      suggest that early alterations in development are central to the disease. Taken
      together, early alterations in DA ontogeny may represent a core feature in the
      pathology of schizophrenia. Such a mechanism could bring together evidence from
      multiple risk factors and genetic vulnerabilities to form a convergent pathway in
      disease pathophysiology. 

PMID- 23882185
TI  - Toward identifying specific roles for G-protein beta and gamma subunit variants
      in olfactory reception.

PMID- 23882186
TI  - Inhibitory synaptic plasticity: spike timing-dependence and putative network
      function.
AB  - While the plasticity of excitatory synaptic connections in the brain has been
      widely studied, the plasticity of inhibitory connections is much less understood.
      Here, we present recent experimental and theoretical findings concerning the
      rules of spike timing-dependent inhibitory plasticity and their putative network
      function. This is a summary of a workshop at the COSYNE conference 2012. 

PMID- 23882187
TI  - Role of maternal thyroid hormones in the developing neocortex and during human
      evolution.
AB  - The importance of thyroid hormones during brain development has been appreciated
      for many decades. In humans, low levels of circulating maternal thyroid hormones,
      e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a
      wide spectrum of severe neurological defects, including neurological cretinism
      characterized by profound neurologic impairment and mental retardation,
      underlining the importance of the maternal thyroid hormone contribution. In fact,
      iodine intake, which is essential for thyroid hormone production in the thyroid
      gland, has been related to the expansion of the brain, associated with the
      increased cognitive capacities during human evolution. Because thyroid hormones
      regulate transcriptional activity of target genes via their nuclear thyroid
      hormone receptors (THRs), even mild and transient changes in maternal thyroid
      hormone levels can directly affect and alter the gene expression profile, and
      thus disturb fetal brain development. Here we summarize how thyroid hormones may
      have influenced human brain evolution through the adaptation to new habitats,
      concomitant with changes in diet and, therefore, iodine intake. Further, we
      review the current picture we gained from experimental studies in rodents on the
      function of maternal thyroid hormones during developmental neurogenesis. We aim
      to evaluate the effects of maternal thyroid hormone deficiency as well as lack of
      THRs and transporters on brain development and function, shedding light on the
      cellular behavior conducted by thyroid hormones. 

PMID- 23882190
TI  - Brain damages in ketamine addicts as revealed by magnetic resonance imaging.
AB  - Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA) glutamate receptors,
      had been used as an anesthetic particularly for pediatric or for cardiac
      patients. Unfortunately, ketamine has become an abusive drug in many parts of the
      world while chronic and prolonged usage led to damages of many organs including
      the brain. However, no studies on possible damages in the brains induced by
      chronic ketamine abuse have been documented in the human via neuroimaging. This
      paper described for the first time via employing magnetic resonance imaging (MRI)
      the changes in ketamine addicts of 0.5-12 years and illustrated the possible
      brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were
      recruited and the results showed that the lesions in the brains of ketamine
      addicts were located in many regions which appeared 2-4 years after ketamine
      addiction. Cortical atrophy was usually evident in the frontal, parietal or
      occipital cortices of addicts. Such study confirmed that many brain regions in
      the human were susceptible to chronic ketamine injury and presented a diffuse
      effect of ketamine on the brain which might differ from other central nervous
      system (CNS) drugs, such as cocaine, heroin, and methamphetamine. 

PMID- 23882189
TI  - Maternal-fetal unit interactions and eutherian neocortical development and
      evolution.
AB  - The conserved brain design that primates inherited from early mammals differs
      from the variable adult brain size and species-specific brain dominances observed
      across mammals. This variability relies on the emergence of specialized cerebral
      cortical regions and sub-compartments, triggering an increase in brain size,
      areal interconnectivity and histological complexity that ultimately lies on the
      activation of developmental programs. Structural placental features are not well
      correlated with brain enlargement; however, several endocrine pathways could be
      tuned with the activation of neuronal progenitors in the proliferative
      neocortical compartments. In this article, we reviewed some mechanisms of
      eutherians maternal-fetal unit interactions associated with brain development and
      evolution. We propose a hypothesis of brain evolution where proliferative
      compartments in primates become activated by "non-classical" endocrine placental
      signals participating in different steps of corticogenesis. Changes in the inner
      placental structure, along with placenta endocrine stimuli over the cortical
      proliferative activity would allow mammalian brain enlargement with a concomitant
      shorter gestation span, as an evolutionary strategy to escape from parent
      offspring conflict. 

PMID- 23882188
TI  - The adaptive significance of adult neurogenesis: an integrative approach.
AB  - Adult neurogenesis in mammals is predominantly restricted to two brain regions,
      the dentate gyrus (DG) of the hippocampus and the olfactory bulb (OB), suggesting
      that these two brain regions uniquely share functions that mediate its adaptive
      significance. Benefits of adult neurogenesis across these two regions appear to
      converge on increased neuronal and structural plasticity that subserves coding of
      novel, complex, and fine-grained information, usually with contextual components
      that include spatial positioning. By contrast, costs of adult neurogenesis appear
      to center on potential for dysregulation resulting in higher risk of brain cancer
      or psychological dysfunctions, but such costs have yet to be quantified directly.
      The three main hypotheses for the proximate functions and adaptive significance
      of adult neurogenesis, pattern separation, memory consolidation, and olfactory
      spatial, are not mutually exclusive and can be reconciled into a simple general
      model amenable to targeted experimental and comparative tests. Comparative
      analysis of brain region sizes across two major social-ecological groups of
      primates, gregarious (mainly diurnal haplorhines, visually-oriented, and in large
      social groups) and solitary (mainly noctural, territorial, and highly reliant on
      olfaction, as in most rodents) suggest that solitary species, but not gregarious
      species, show positive associations of population densities and home range sizes
      with sizes of both the hippocampus and OB, implicating their functions in social
      territorial systems mediated by olfactory cues. Integrated analyses of the
      adaptive significance of adult neurogenesis will benefit from experimental
      studies motivated and structured by ecologically and socially relevant selective
      contexts. 

PMID- 23882191
TI  - Functional roles of the thalamus for language capacities.
AB  - Early biological concepts of language were predominantly corticocentric, but over
      the last decades biolinguistic research, equipped with new technical
      possibilities, has drastically changed this view. To date, connectionist models,
      conceiving linguistic skills as corticobasal network activities, dominate our
      understanding of the neural basis of language. However, beyond the notion of an
      involvement of the thalamus and, in most cases also, the basal ganglia (BG) in
      linguistic operations, specific functions of the respective depth structures
      mostly remain rather controversial. In this review, some of these issues shall be
      discussed, particularly the functional configuration of basal network components
      and the language specificity of subcortical supporting activity. Arguments will
      be provided for a primarily cortico-thalamic language network. In this view, the
      thalamus does not engage in proper linguistic operations, but rather acts as a
      central monitor for language-specific cortical activities, supported by the BG in
      both perceptual and productive language execution. 

PMID- 23882193
TI  - The rates of change of the stochastic trajectories of acceleration variability
      are a good predictor of normal aging and of the stage of Parkinson's disease.
AB  - The accelerometer data from mobile smart phones provide stochastic trajectories
      that change over time. This rate of change is unique to each person and can be
      well-characterized by the continuous two-parameter family of Gamma probability
      distributions. Accordingly, on the Gamma plane each participant can be uniquely
      localized by the shape and the scale parameters of the Gamma probability
      distribution. The scatter of such points contains information that can
      unambiguously separate the normal controls (NC) from those patients with
      Parkinson's disease (PD) that are at a later stage of the disease. In general
      normal aging seems conducive of more predictable patterns of variation in the
      accelerometer data. Yet this trend breaks down in PD where the statistical
      signatures seem to be a more relevant predictor of the stage of the disease.
      Those patients at a later stage of the disease have more random and noisier
      patterns than those in the earlier stages, whose statistics resemble those of the
      older NC. Overall the peak rates of change of the stochastic trajectories of the
      accelerometer are a good predictor of the stage of PD and of the age of a
      "normally" aging individual. 

PMID- 23882192
TI  - Autism as a developmental disorder in intentional movement and affective
      engagement.
AB  - We review evidence that autistic spectrum disorders have their origin in early
      prenatal failure of development in systems that program timing, serial
      coordination and prospective control of movements, and that regulate affective
      evaluations of experiences. There are effects in early infancy, before medical
      diagnosis, especially in motor sequencing, selective or exploratory attention,
      affective expression and intersubjective engagement with parents. These are
      followed by retardation of cognitive development and language learning in the
      second or third year, which lead to a diagnosis of ASD. The early signs relate to
      abnormalities that have been found in brain stem systems and cerebellum in the
      embryo or early fetal stage, before the cerebral neocortex is functional, and
      they have clear consequences in infancy when neocortical systems are intensively
      elaborated. We propose, with evidence of the disturbances of posture, locomotion
      and prospective motor control in children with autism, as well as of their facial
      expression of interest and affect, and attention to other persons' expressions,
      that examination of the psychobiology of motor affective disorders, rather than
      later developing cognitive or linguistic ones, may facilitate early diagnosis.
      Research in this area may also explain how intense interaction, imitation or
      "expressive art" therapies, which respond intimately with motor activities, are
      effective at later stages. Exceptional talents of some autistic people may be
      acquired compensations for basic problems with expectant self-regulations of
      movement, attention and emotion. 

PMID- 23882195
TI  - Eccentricity dependent auditory enhancement of visual stimulus detection but not
      discrimination.
AB  - Sensory perception is enhanced by the complementary information provided by our
      different sensory modalities and even apparently task irrelevant stimuli in one
      modality can facilitate performance in another. While perception in general
      comprises both, the detection of sensory objects as well as their discrimination
      and recognition, most studies on audio-visual interactions have focused on either
      of these aspects. However, previous evidence, neuroanatomical projections between
      early sensory cortices and computational mechanisms suggest that sounds might
      differentially affect visual detection and discrimination and differentially at
      central and peripheral retinal locations. We performed an experiment to directly
      test this by probing the enhancement of visual detection and discrimination by
      auxiliary sounds at different visual eccentricities and within the same subjects.
      Specifically, we quantified the enhancement provided by sounds that reduce the
      overall uncertainty about the visual stimulus beyond basic multisensory co
      stimulation. This revealed a general trend for stronger enhancement at peripheral
      locations in both tasks, but a statistically significant effect only for
      detection and only at peripheral locations. Overall this suggests that there are
      topographic differences in the auditory facilitation of basic visual processes
      and that these may differentially affect basic aspects of visual recognition. 

PMID- 23882194
TI  - Sensory-motor problems in Autism.
AB  - Despite being largely characterized as a social and cognitive disorder, strong
      evidence indicates the presence of significant sensory-motor problems in Autism
      Spectrum Disorder (ASD). This paper outlines our progression from initial, broad
      assessment using the Movement Assessment Battery for Children (M-ABC2) to
      subsequent targeted kinematic assessment. In particular, pronounced ASD
      impairment seen in the broad categories of manual dexterity and ball skills was
      found to be routed in specific difficulties on isolated tasks, which were
      translated into focused experimental assessment. Kinematic results from both
      subsequent studies highlight impaired use of perception-action coupling to guide,
      adapt and tailor movement to task demands, resulting in inflexible and rigid
      motor profiles. In particular difficulties with the use of temporal adaption are
      shown, with "hyperdexterity" witnessed in ballistic movement profiles, often at
      the cost of spatial accuracy and task performance. By linearly progressing from
      the use of a standardized assessment tool to targeted kinematic assessment, clear
      and defined links are drawn between measureable difficulties and underlying
      sensory-motor assessment. Results are specifically viewed in-light of perception
      action coupling and its role in early infant development suggesting that rather
      than being "secondary" level impairment, sensory-motor problems may be
      fundamental in the progression of ASD. This logical and systematic process thus
      allows a further understanding into the potential root of observable motor
      problems in ASD; a vital step if underlying motor problems are to be considered a
      fundamental aspect of autism and allow a route of non-invasive preliminary
      diagnosis. 

PMID- 23882196
TI  - Working memory management and predicted utility.
AB  - Given the limited capacity of working memory (WM), its resources should be
      allocated strategically. One strategy is filtering, whereby access to WM is
      granted preferentially to items with the greatest utility. However, reallocation
      of WM resources might be required if the utility of maintained information
      subsequently declines. Here, we present behavioral, computational, and
      neuroimaging evidence that human participants track changes in the predicted
      utility of information in WM. First, participants demonstrated behavioral costs
      when the utility of items already maintained in WM declined and resources should
      be reallocated. An adapted Q-learning model indicated that these costs scaled
      with the historical utility of individual items. Finally, model-based
      neuroimaging demonstrated that frontal cortex tracked the utility of items to be
      maintained in WM, whereas ventral striatum tracked changes in the utility of
      items maintained in WM to the degree that these items are no longer useful. Our
      findings suggest that frontostriatal mechanisms track the utility of information
      in WM, and that these dynamics may predict delays in the removal of information
      from WM. 

PMID- 23882197
TI  - Ethanol-derived acetaldehyde: pleasure and pain of alcohol mechanism of action.
AB  - Acetaldehyde (ACD), the first metabolite of ethanol (EtOH), has been implicated
      in several actions of alcohol, including its reinforcing effects. Previously
      considered an aversive compound, ACD was useful in alcoholic's pharmacological
      treatment aimed at discouraging alcohol drinking. However, it has recently been
      shown that EtOH-derived ACD is necessary for EtOH-induced place preference and
      self-administration, thereby suggesting a possible involvement of ACD in EtOH
      motivational properties. In addition, EtOH-stimulating properties on DA neurons
      are prevented by pharmacological blockade of local catalase H2O2 system, the main
      metabolic step for biotransformation of EtOH into ACD within the central nervous
      system. It was further shown that pretreatment with thiol compounds, like L
      Cysteine or D-Penicillamine, reduced EtOH and ACD-induced motivational effects,
      in fact preventing self-administration of both EtOH and ACD, thus suggesting a
      possible role for ACD as a biomarker useful in evaluating potential innovative
      treatments of alcohol abuse. These findings suggest a key role of ACD in the EtOH
      reinforcing effects. In the present paper we review the role of EtOH-derived ACD
      in the reinforcing effects of EtOH and the possibility that ACD may serve as a
      therapeutically targetable biomarker in the search for novel treatments in
      alcohol abuse and alcoholism. 

PMID- 23882198
TI  - Alteration in forward model prediction of sensory outcome of motor action in
      focal hand dystonia.
AB  - Focal hand dystonia in musicians is a movement disorder affecting highly trained
      movements. Rather than being a pure motor disorder related to movement execution
      only, movement planning, error prediction, and sensorimotor integration are also
      impaired. Internal models (IMs), of which two types, forward and inverse models
      have been described and most likely processed in the cerebellum, are known to be
      involved in these tasks. Recent results indicate that the cerebellum may be
      involved in the pathophysiology of focal dystonia (FD). Thus, the aim of our
      study was to investigate whether an IM deficit plays a role in FD. We focused on
      the forward model (FM), which predicts sensory consequences of motor commands and
      allows the discrimination between external sensory input and input deriving from
      motor action. We investigated 19 patients, aged 19-59 and 19 healthy musicians
      aged 19-36 as controls. Tactile stimuli were applied to fingers II-V of both
      hands by the experimenter or the patient. After each stimulus the participant
      rated the stimulus intensity on a scale between 0 (no sensation) and 1 (maximal
      intensity). The difference of perceived intensity between self- and externally
      applied (EA) stimuli was then calculated for each finger. For assessing
      differences between patients and controls we performed a cluster analysis of the
      affected hand and the corresponding hand of the controls using the fingers II-V
      as variables in a 4-dimensional hyperspace (chance level = 0.5). Using a cluster
      analysis, we found a correct classification of the affected finger in 78.9-94.7%.
      There was no difference between patients and healthy controls of the absolute
      value of the perceived stimulus intensity. Our results suggest an altered FM
      function in focal hand dystonia. It has the potential of suggesting a neural
      correlate within the cerebellum and of helping integrate findings with regard to
      altered sensorimotor processing and altered prediction in FD in a single
      framework. 

PMID- 23882199
TI  - Flexibility of movement organization in piano performance.
AB  - Piano performance involves a large repertoire of highly skilled movements. The
      acquisition of these exceptional skills despite innate neural and biomechanical
      constraints requires a sophisticated interaction between plasticity of the neural
      system and organization of a redundant number of degrees of freedom (DOF) in the
      motor system. Neuroplasticity subserving virtuosity of pianists has been
      documented in neuroimaging studies investigating effects of long-term piano
      training on structure and function of the cortical and subcortical regions. By
      contrast, recent behavioral studies have advanced the understanding of
      neuromuscular strategies and biomechanical principles behind the movement
      organization that enables skilled piano performance. Here we review the motor
      control and biomechanics literature, introducing the importance of describing
      motor behaviors not only for understanding mechanisms responsible for skillful
      motor actions in piano playing, but also for advancing diagnosis and
      rehabilitation of movement disorders caused by extensive piano practice. 

PMID- 23882200
TI  - Optic ataxia as a model to investigate the role of the posterior parietal cortex
      in visually guided action: evidence from studies of patient M.H.
AB  - Optic ataxia is a neuropsychological disorder that affects the ability to
      interact with objects presented in the visual modality following either
      unilateral or bilateral lesions of the posterior parietal cortex (PPC). Patients
      with optic ataxia fail to reach accurately for objects, particularly when they
      are presented in peripheral vision. The present review will focus on a series of
      experiments performed on patient M.H. Following a lesion restricted largely to
      the left PPC, he developed mis-reaching behavior when using his contralesional
      right arm for movements directed toward the contralesional (right) visual half
      field. Given the clear-cut specificity of this patient's deficit, whereby
      reaching actions are essentially spared when executed toward his ipsilateral
      space or when using his left arm, M.H. provides a valuable "experiment of nature"
      for investigating the role of the PPC in performing different visually guided
      actions. In order to address this, we used kinematic measurement techniques to
      investigate M.H.'s reaching and grasping behavior in various tasks. Our
      experiments support the idea that optic ataxia is highly function-specific: it
      affects a specific sub-category of visually guided actions (reaching but not
      grasping), regardless of their specific end goal (both reaching toward an object
      and reaching to avoid an obstacle); and finally, is independent of the limb used
      to perform the action (whether the arm or the leg). Critically, these results are
      congruent with recent functional MRI experiments in neurologically intact
      subjects which suggest that the PPC is organized in a function-specific, rather
      than effector-specific, manner with different sub-portions of its mantle devoted
      to guiding actions according to their specific end-goal (reaching, grasping, or
      looking), rather than according to the effector used to perform them (leg, arm,
      hand, or eyes). 

PMID- 23882202
TI  - Dissociations between spatial-attentional processes within parietal cortex:
      insights from hybrid spatial cueing and change detection paradigms.
AB  - Spatial cueing has been used by many different groups under multiple forms to
      study spatial attention processes. We will present evidence obtained in brain
      damaged patients and healthy volunteers using a variant of this paradigm, the
      hybrid spatial cueing paradigm, which, besides single-target trials with valid
      and invalid cues, also contains trials where a target is accompanied by a
      contralateral competing stimulus (competition trials). This allows one to study
      invalidity-related processes and selection between competing stimuli within the
      same paradigm. In brain-damaged patients, lesions confined to the intraparietal
      sulcus result in contralesional attentional deficits, both during competition and
      invalid trials, according to a pattern that does not differ from that observed
      following inferior parietal lesions. In healthy volunteers, however, selection
      between competing stimuli and invalidity-related processes are partially
      dissociable, the former relying mainly on cytoarchitectonic areas hIP1-3 in the
      intraparietal sulcus, the latter on cytoarchitectonic area PF in the right
      inferior parietal lobule. The activity profile in more posterior inferior
      parietal areas PFm and PGa, does not distinguish between both types of trials.
      The functional account for right PF and adjacent areas is further constrained by
      the activity profile observed during other experimental paradigms. In a change
      detection task with variable target and distracter set size, for example, these
      inferior parietal areas show highest activity when the stimulus array consists of
      only one single target, while the intraparietal sulcus show increased activity as
      the array contains more targets and distracters. Together, these findings lead us
      to the hypothesis that right PF functions as a target singleton detector, which
      is activated when a target stands out from the background, referring both to the
      temporal background (expectancy) and the momentaneous background (stimulus-driven
      saliency). 

PMID- 23882201
TI  - Neural markers of errors as endophenotypes in neuropsychiatric disorders.
AB  - Learning from errors is fundamental to adaptive human behavior. It requires
      detecting errors, evaluating what went wrong, and adjusting behavior accordingly.
      These dynamic adjustments are at the heart of behavioral flexibility and
      accumulating evidence suggests that deficient error processing contributes to
      maladaptively rigid and repetitive behavior in a range of neuropsychiatric
      disorders. Neuroimaging and electrophysiological studies reveal highly reliable
      neural markers of error processing. In this review, we evaluate the evidence that
      abnormalities in these neural markers can serve as sensitive endophenotypes of
      neuropsychiatric disorders. We describe the behavioral and neural hallmarks of
      error processing, their mediation by common genetic polymorphisms, and
      impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum
      disorders. We conclude that neural markers of errors meet several important
      criteria as endophenotypes including heritability, established neuroanatomical
      and neurochemical substrates, association with neuropsychiatric disorders,
      presence in syndromally-unaffected family members, and evidence of genetic
      mediation. Understanding the mechanisms of error processing deficits in
      neuropsychiatric disorders may provide novel neural and behavioral targets for
      treatment and sensitive surrogate markers of treatment response. Treating error
      processing deficits may improve functional outcome since error signals provide
      crucial information for flexible adaptation to changing environments. Given the
      dearth of effective interventions for cognitive deficits in neuropsychiatric
      disorders, this represents a potentially promising approach. 

PMID- 23882204
TI  - On the role of crossmodal prediction in audiovisual emotion perception.
AB  - Humans rely on multiple sensory modalities to determine the emotional state of
      others. In fact, such multisensory perception may be one of the mechanisms
      explaining the ease and efficiency by which others' emotions are recognized. But
      how and when exactly do the different modalities interact? One aspect in
      multisensory perception that has received increasing interest in recent years is
      the concept of cross-modal prediction. In emotion perception, as in most other
      settings, visual information precedes the auditory information. Thereby, leading
      in visual information can facilitate subsequent auditory processing. While this
      mechanism has often been described in audiovisual speech perception, so far it
      has not been addressed in audiovisual emotion perception. Based on the current
      state of the art in (a) cross-modal prediction and (b) multisensory emotion
      perception research, we propose that it is essential to consider the former in
      order to fully understand the latter. Focusing on electroencephalographic (EEG)
      and magnetoencephalographic (MEG) studies, we provide a brief overview of the
      current research in both fields. In discussing these findings, we suggest that
      emotional visual information may allow more reliable predicting of auditory
      information compared to non-emotional visual information. In support of this
      hypothesis, we present a re-analysis of a previous data set that shows an inverse
      correlation between the N1 EEG response and the duration of visual emotional, but
      not non-emotional information. If the assumption that emotional content allows
      more reliable predicting can be corroborated in future studies, cross-modal
      prediction is a crucial factor in our understanding of multisensory emotion
      perception. 

PMID- 23882203
TI  - A comprehensive review of auditory verbal hallucinations: lifetime prevalence,
      correlates and mechanisms in healthy and clinical individuals.
AB  - Over the years, the prevalence of auditory verbal hallucinations (AVHs) have been
      documented across the lifespan in varied contexts, and with a range of potential
      long-term outcomes. Initially the emphasis focused on whether AVHs conferred risk
      for psychosis. However, recent research has identified significant differences in
      the presentation and outcomes of AVH in patients compared to those in non
      clinical populations. For this reason, it has been suggested that auditory
      hallucinations are an entity by themselves and not necessarily indicative of
      transition along the psychosis continuum. This review will examine the
      presentation of auditory hallucinations across the life span, as well as in
      various clinical groups. The stages described include childhood, adolescence,
      adult non-clinical populations, hypnagogic/hypnopompic experiences, high
      schizotypal traits, schizophrenia, substance induced AVH, AVH in epilepsy, and
      AVH in the elderly. In children, need for care depends upon whether the child
      associates the voice with negative beliefs, appraisals and other symptoms of
      psychosis. This theme appears to carry right through to healthy voice hearers in
      adulthood, in which a negative impact of the voice usually only exists if the
      individual has negative experiences as a result of their voice(s). This includes
      features of the voices such as the negative content, frequency, and emotional
      valence as well as anxiety and depression, independently or caused by voices
      presence. It seems possible that the mechanisms which maintain AVH in non
      clinical populations are different from those which are behind AVH presentations
      in psychotic illness. For example, the existence of maladaptive coping strategies
      in patient populations is one significant difference between clinical and non
      clinical groups which is associated with a need for care. Whether or not these
      mechanisms start out the same and have differential trajectories is not yet
      evidenced. Future research needs to focus on the comparison of underlying factors
      and mechanisms that lead to the onset of AVH in both patient and non-clinical
      populations. 

PMID- 23882207
TI  - Auditory habituation to simple tones: reduced evidence for habituation in
      children compared to adults.
AB  - Habituation-the response decrement to repetitively presented stimulation-is a
      basic cognitive capability and suited to investigate development and integrity of
      the human brain. To evaluate the developmental process of auditory habituation,
      the current study used magnetoencephalography (MEG) to investigate auditory
      habituation, dishabituation and stimulus specificity in children and adults and
      compared the results between age groups. Twenty-nine children (M age = 9.69
      years, SD +/- 0.47) and 14 adults (M age = 29.29 years, SD +/- 3.47) participated
      in the study and passively listened to a habituation paradigm consisting of 100
      trains of tones which were composed of five 500 Hz tones, one 750 Hz tone
      (dishabituator) and another two 500 Hz tones, respectively while focusing their
      attention on a silent movie. Adults showed the expected habituation and stimulus
      specificity within-trains while no response decrement was found between trains.
      Sensory adaptation or fatigue as a source for response decrement in adults is
      unlikely due to the strong reaction to the dishabituator (stimulus specificity)
      and strong mismatch negativity (MMN) responses. However, in children neither
      habituation nor dishabituation or stimulus specificity could be found within
      trains, response decrement was found across trains. It can be speculated that the
      differences between children and adults are linked to differences in stimulus
      processing due to attentional processes. This study shows developmental
      differences in task-related brain activation and discusses the possible influence
      of broader concepts such as attention, which should be taken into account when
      comparing performance in an identical task between age groups. 

PMID- 23882206
TI  - How interpersonal power affects empathic accuracy: differential roles of
      mentalizing vs. mirroring?
AB  - Empathic accuracy (EA)-the correct assessment of the affective states and
      thoughts of a social partner-affects social behavior and the outcome of
      interpersonal interactions. Growing evidence has shown that interpersonal power
      of a perceiver affects EA when assessing a target. This picture, however, is not
      obvious; there is evidence supporting both the idea that power can improve EA or
      impair it. Moreover, the mechanisms through which high power individuals are more
      (or less) accurate at reading others' minds are unknown. The present article
      provides a new perspective on the power-EA link by investigating how two core
      abilities involved in EA, mentalizing and mirroring, can explain when and how
      power is related to EA. The inclusion of findings from neuroimaging studies on
      mentalizing and mirroring adds a cognitive neuroscience perspective to the power
      EA research that has traditionally been conducted in a social psychological
      framework. The extent to which a given EA-test requires mentalizing or mirroring
      and the way power affects both of them could explain the contrasting findings. In
      addition, the analysis of the neural substrates of mentalizing and mirroring may
      provide new insight into the relationship between power and EA. 

PMID- 23882205
TI  - The visual mismatch negativity elicited with visual speech stimuli.
AB  - The visual mismatch negativity (vMMN), deriving from the brain's response to
      stimulus deviance, is thought to be generated by the cortex that represents the
      stimulus. The vMMN response to visual speech stimuli was used in a study of the
      lateralization of visual speech processing. Previous research suggested that the
      right posterior temporal cortex has specialization for processing simple non
      speech face gestures, and the left posterior temporal cortex has specialization
      for processing visual speech gestures. Here, visual speech consonant-vowel (CV)
      stimuli with controlled perceptual dissimilarities were presented in an
      electroencephalography (EEG) vMMN paradigm. The vMMNs were obtained using the
      comparison of event-related potentials (ERPs) for separate CVs in their roles as
      deviant vs. their roles as standard. Four separate vMMN contrasts were tested,
      two with the perceptually far deviants (i.e., "zha" or "fa") and two with the
      near deviants (i.e., "zha" or "ta"). Only far deviants evoked the vMMN response
      over the left posterior temporal cortex. All four deviants evoked vMMNs over the
      right posterior temporal cortex. The results are interpreted as evidence that the
      left posterior temporal cortex represents speech contrasts that are perceived as
      different consonants, and the right posterior temporal cortex represents face
      gestures that may not be perceived as different CVs. 

PMID- 23882208
TI  - Long-lasting amelioration of walking trajectory in neglect after prismatic
      adaptation.
AB  - In the present study we explored the effect of prismatic adaptation (PA) applied
      to the upper right limb on the walking trajectory of a neglect patient with more
      severe neglect in far than in near space. The patient was asked to bisect a line
      fixed to the floor by walking across it before and after four sessions of PA
      distributed over a time frame of 67 days. Gait path was analyzed by means of an
      optoelectronic motion analysis system. The walking trajectory improved following
      PA and the result was maintained at follow-up, 15 months after treatment. The
      improvement was greater for the predicted bisection error (estimated on the basis
      of the trajectory extrapolated from the first walking step) than for the observed
      bisection error (measured at line bisection). These results show that PA may act
      on high level spatial representation of gait trajectory rather than on lower
      level sensory-motor gait components and suggest that PA may have a long-lasting
      rehabilitative effect on neglect patients showing a deviated walking trajectory. 

PMID- 23882209
TI  - On the all-or-none rule of conscious perception.

PMID- 23882210
TI  - What Can the Organization of the Brain's Default Mode Network Tell us About Self
      Knowledge?
AB  - Understanding ourselves has been a fundamental topic for psychologists and
      philosophers alike. In this paper we review the evidence linking specific brain
      structures to self-reflection. The brain regions most associated with self
      reflection are the posterior cingulate and medial prefrontal (mPFC) cortices,
      together known as the cortical midline structures (CMSs). We review evidence
      arguing that self-reflection is special in memory, while noting that these brain
      regions are often engaged when we think about others in our social worlds. Based
      on the CMSs' patterns of connectivity and activity, we speculate about three
      possible interpretations of their role in supporting self-reflection that are
      somewhat overlapping, and not intended to be mutually exclusive. First, self may
      be a powerful, but ordinary case for a cognitive system specialized for thinking
      about people. Second, mPFC may serve as a processing "hub," binding together
      information from all sensory modalities with internally generated information.
      Third, mPFC may serve as a cortical director of thought, helping to guide moment
      by-moment conscious processing. Suggestions are made for future research avenues
      aimed at testing such possibilities. 

PMID- 23882211
TI  - Interplay of two signals in a neuron with heterogeneous synaptic short-term
      plasticity.
AB  - Signals from different sensory modalities may converge on a single neuron. We
      study theoretically a setup in which one signal is transmitted via facilitating
      synapses (F signal) and another via depressing synapses (D signal). When both
      signals are present, the postsynaptic cell preferentially encodes information
      about slow components of the F signal and fast components of the D signal,
      whereas for a single signal, transmission is broadband. We also show that, in the
      fluctuation-driven regime, the rate of information transmission may be increased
      through stochastic resonance (SR). Remarkably, the role of the beneficial noise
      is played by another signal, which is itself represented in the spike train of
      the postsynaptic cell. 

PMID- 23882212
TI  - Modulation of epileptic activity by deep brain stimulation: a model-based study
      of frequency-dependent effects.
AB  - A number of studies showed that deep brain stimulation (DBS) can modulate the
      activity in the epileptic brain and that a decrease of seizures can be achieved
      in "responding" patients. In most of these studies, the choice of stimulation
      parameters is critical to obtain desired clinical effects. In particular, the
      stimulation frequency is a key parameter that is difficult to tune. A reason is
      that our knowledge about the frequency-dependant mechanisms according to which
      DBS indirectly impacts the dynamics of pathological neuronal systems located in
      the neocortex is still limited. We address this issue using both computational
      modeling and intracerebral EEG (iEEG) data. We developed a macroscopic (neural
      mass) model of the thalamocortical network. In line with already-existing models,
      it includes interconnected neocortical pyramidal cells and interneurons,
      thalamocortical cells and reticular neurons. The novelty was to introduce, in the
      thalamic compartment, the biophysical effects of direct stimulation. Regarding
      clinical data, we used a quite unique data set recorded in a patient (drug
      resistant epilepsy) with a focal cortical dysplasia (FCD). In this patient, DBS
      strongly reduced the sustained epileptic activity of the FCD for low-frequency
      (LFS, < 2 Hz) and high-frequency stimulation (HFS, > 70 Hz) while intermediate
      frequency stimulation (IFS, around 50 Hz) had no effect. Signal processing,
      clustering, and optimization techniques allowed us to identify the necessary
      conditions for reproducing, in the model, the observed frequency-dependent
      stimulation effects. Key elements which explain the suppression of epileptic
      activity in the FCD include: (a) feed-forward inhibition and synaptic short-term
      depression of thalamocortical connections at LFS, and (b) inhibition of the
      thalamic output at HFS. Conversely, modeling results indicate that IFS favors
      thalamic oscillations and entrains epileptic dynamics. 

PMID- 23882213
TI  - Rapid, parallel path planning by propagating wavefronts of spiking neural
      activity.
AB  - Efficient path planning and navigation is critical for animals, robotics,
      logistics and transportation. We study a model in which spatial navigation
      problems can rapidly be solved in the brain by parallel mental exploration of
      alternative routes using propagating waves of neural activity. A wave of spiking
      activity propagates through a hippocampus-like network, altering the synaptic
      connectivity. The resulting vector field of synaptic change then guides a
      simulated animal to the appropriate selected target locations. We demonstrate
      that the navigation problem can be solved using realistic, local synaptic
      plasticity rules during a single passage of a wavefront. Our model can find
      optimal solutions for competing possible targets or learn and navigate in
      multiple environments. The model provides a hypothesis on the possible
      computational mechanisms for optimal path planning in the brain, at the same time
      it is useful for neuromorphic implementations, where the parallelism of
      information processing proposed here can fully be harnessed in hardware. 

PMID- 23882214
TI  - Zinc homeostasis and neurodegenerative disorders.
AB  - Zinc is an essential trace element, whose importance to the function of the
      central nervous system (CNS) is increasingly being appreciated. Alterations in
      zinc dyshomeostasis has been suggested as a key factor in the development of
      several neuropsychiatric disorders. In the CNS, zinc occurs in two forms: the
      first being tightly bound to proteins and, secondly, the free, cytoplasmic, or
      extracellular form found in presynaptic vesicles. Under normal conditions, zinc
      released from the synaptic vesicles modulates both ionotropic and metabotropic
      post-synaptic receptors. While under clinical conditions such as traumatic brain
      injury, stroke or epilepsy, the excess influx of zinc into neurons has been found
      to result in neurotoxicity and damage to postsynaptic neurons. On the other hand,
      a growing body of evidence suggests that a deficiency, rather than an excess, of
      zinc leads to an increased risk for the development of neurological disorders.
      Indeed, zinc deficiency has been shown to affect neurogenesis and increase
      neuronal apoptosis, which can lead to learning and memory deficits. Altered zinc
      homeostasis is also suggested as a risk factor for depression, Alzheimer's
      disease (AD), aging, and other neurodegenerative disorders. Under normal CNS
      physiology, homeostatic controls are put in place to avoid the accumulation of
      excess zinc or its deficiency. This cellular zinc homeostasis results from the
      actions of a coordinated regulation effected by different proteins involved in
      the uptake, excretion and intracellular storage/trafficking of zinc. These
      proteins include membranous transporters (ZnT and Zip) and metallothioneins (MT)
      which control intracellular zinc levels. Interestingly, alterations in ZnT and MT
      have been recently reported in both aging and AD. This paper provides an overview
      of both clinical and experimental evidence that implicates a dysfunction in zinc
      homeostasis in the pathophysiology of depression, AD, and aging. 

PMID- 23882215
TI  - Metalloproteomics: principles, challenges and applications to neurodegeneration.
AB  - Trace elements are required for a variety of normal biological functions. As our
      understanding of neurodegenerative disease advances we are identifying a number
      of metalloenzymes involved in disease process. Thus, the future of metals in
      neurobiology will rely more on detailed information regarding what metalloenzymes
      are present and how they are involved in the pathophysiology of disease. To gain
      this detailed information, we will rely less on bulk measures of the amount of a
      trace elements in a particular tissue and turn to metalloproteomic techniques to
      help elucidate both metalloprotein structure and function. Recent advances in
      metalloproteomics will translate to a richer understanding of the mechanism and
      precise role of metalloenzymes and proteins in the brain. 

PMID- 23882217
TI  - Together and apart: inhibition of DNA synthesis by connexin-43 and its
      relationship to transforming growth factor beta.
AB  - The membrane and channel protein connexin-43 (Cx43), as well as the cytokine
      transforming growth factor (TGF) beta, suppress proliferative growth in
      cardiomyocytes and other cell types. Previously we showed that the inhibitory
      effect of Cx43 is canceled when Cx43 becomes phosphorylated at serine (S) 262 in
      response to mitogen stimulation. We have now asked if the TGFbeta-triggered
      inhibition of DNA synthesis is associated with changes in Cx43 phosphorylation at
      S262. Conversely, we investigated if inhibition of DNA synthesis by overexpressed
      Cx43 is dependent on engaging TGFbeta signal transduction. We report that TGFbeta
      acutely prevented mitogen-induced Cx43 phosphorylation at S262, while chronic
      inhibition of TGFbeta signal transduction raised baseline levels of endogenous
      phospho-S262-Cx43 without affecting total Cx43. Inhibition of baseline TGFbeta
      signal transduction through (a) inhibiting TGFbeta receptor I (TGFbetaRI) with
      SB431542, (b) inhibiting TGFbeta receptor II (TGFbetaRII) by overexpressing
      dominant-negative (DN) TGFbetaRII, (c) inhibiting the downstream signaling
      mediator Smad2 by overexpressing DN Smad2, each separately increased baseline
      cardiomyocyte DNA synthesis, but could not reverse DNA synthesis inhibition by
      overexpressed Cx43. It is suggested that inhibition of cardiomyocyte DNA
      synthesis by TGFbeta/TGFbetaRI/II/phospho-Smad2 signaling is mediated, at least
      in part, by reducing endogenous phospho-S262-Cx43 levels. 

PMID- 23882216
TI  - Connexin and pannexin hemichannels in brain glial cells: properties,
      pharmacology, and roles.
AB  - Functional interaction between neurons and glia is an exciting field that has
      expanded tremendously during the past decade. Such partnership has multiple
      impacts on neuronal activity and survival. Indeed, numerous findings indicate
      that glial cells interact tightly with neurons in physiological as well as
      pathological situations. One typical feature of glial cells is their high
      expression level of gap junction protein subunits, named connexins (Cxs), thus
      the membrane channels they form may contribute to neuroglial interaction that
      impacts neuronal activity and survival. While the participation of gap junction
      channels in neuroglial interactions has been regularly reviewed in the past, the
      other channel function of Cxs, i.e., hemichannels located at the cell surface,
      has only recently received attention. Gap junction channels provide the basis for
      a unique direct cell-to-cell communication, whereas Cx hemichannels allow the
      exchange of ions and signaling molecules between the cytoplasm and the
      extracellular medium, thus supporting autocrine and paracrine communication
      through a process referred to as "gliotransmission," as well as uptake and
      release of metabolites. More recently, another family of proteins, termed
      pannexins (Panxs), has been identified. These proteins share similar membrane
      topology but no sequence homology with Cxs. They form multimeric membrane
      channels with pharmacology somewhat overlapping with that of Cx hemichannels.
      Such duality has led to several controversies in the literature concerning the
      identification of the molecular channel constituents (Cxs versus Panxs) in glia.
      In the present review, we update and discuss the knowledge of Cx hemichannels and
      Panx channels in glia, their properties and pharmacology, as well as the
      understanding of their contribution to neuroglial interactions in brain health
      and disease. 

PMID- 23882218
TI  - The irradiated tumor microenvironment: role of tumor-associated macrophages in
      vascular recovery.
AB  - Radiotherapy is an important modality used in the treatment of more than 50% of
      cancer patients in the US. However, despite sophisticated techniques for
      radiation delivery as well as the combination of radiation with chemotherapy,
      tumors can recur. Thus, any method of improving the local control of the primary
      tumor by radiotherapy would produce a major improvement in the curability of
      cancer patients. One of the challenges in the field is to understand how the
      tumor vasculature can regrow after radiation in order to support tumor
      recurrence, as it is unlikely that any of the endothelial cells within the tumor
      could survive the doses given in a typical radiotherapy regimen. There is now
      considerable evidence from both preclinical and clinical studies that the tumor
      vasculature can be restored following radiotherapy from an influx of circulating
      cells consisting primarily of bone marrow derived monocytes and macrophages. The
      radiation-induced influx of bone marrow derived cells (BMDCs) into tumors can be
      prevented through the blockade of various cytokine pathways and such strategies
      can inhibit tumor recurrence. However, the post-radiation interactions between
      surviving tumor cells, recruited immune cells, and the remaining stroma remain
      poorly defined. While prior studies have described the monocyte/macrophage
      inflammatory response within normal tissues and in the tumor microenvironment,
      less is known about this response with respect to a tumor after radiation
      therapy. The goal of this review is to summarize existing research studies to
      provide an understanding of how the myelomonocytic lineage may influence vascular
      recovery within the irradiated tumor microenvironment. 

PMID- 23882219
TI  - Using neurolipidomics to identify phospholipid mediators of synaptic
      (dys)function in Alzheimer's Disease.
AB  - Not all of the mysteries of life lie in our genetic code. Some can be found
      buried in our membranes. These shells of fat, sculpted in the central nervous
      system into the cellular (and subcellular) boundaries of neurons and glia, are
      themselves complex systems of information. The diversity of neural phospholipids,
      coupled with their chameleon-like capacity to transmute into bioactive molecules,
      provides a vast repertoire of immediate response second messengers. The effects
      of compositional changes on synaptic function have only begun to be appreciated.
      Here, we mined 29 neurolipidomic datasets for changes in neuronal membrane
      phospholipid metabolism in Alzheimer's Disease (AD). Three overarching metabolic
      disturbances were detected. We found that an increase in the hydrolysis of
      platelet activating factor precursors and ethanolamine-containing plasmalogens,
      coupled with a failure to regenerate relatively rare alkyl-acyl and alkenyl-acyl
      structural phospholipids, correlated with disease severity. Accumulation of
      specific bioactive metabolites [i.e., PC(O-16:0/2:0) and PE(P-16:0/0:0)] was
      associated with aggravating tau pathology, enhancing vesicular release, and
      signaling neuronal loss. Finally, depletion of PI(16:0/20:4), PI(16:0/22:6), and
      PI(18:0/22:6) was implicated in accelerating Abeta42 biogenesis. Our analysis
      further suggested that converging disruptions in platelet activating factor,
      plasmalogen, phosphoinositol, phosphoethanolamine (PE), and docosahexaenoic acid
      metabolism may contribute mechanistically to catastrophic vesicular depletion,
      impaired receptor trafficking, and morphological dendritic deformation. Together,
      this analysis supports an emerging hypothesis that aberrant phospholipid
      metabolism may be one of multiple critical determinants required for Alzheimer
      disease conversion. 

PMID- 23882220
TI  - Endocrine pancreatic development: impact of obesity and diet.
AB  - During embryonic development, multipotent endodermal cells differentiate to form
      the pancreas. Islet cell clusters arising from the pancreatic bud form the acini
      tissue and exocrine ducts whilst pancreatic islets form around the edges of the
      clusters. The successive steps of islet differentiation are controlled by a
      complex network of transcription factors and signals that influence cell
      differentiation, growth and lineage. A Westernized lifestyle has led to an
      increased consumption of a high saturated fat diet, and an increase in maternal
      obesity. The developing fetus is highly sensitive to the intrauterine
      environment, therefore any alteration in maternal nutrition during gestation and
      lactation which affects the in-utero environment during the key developmental
      phases of the pancreas may change the factors controlling beta-cell development
      and beta-cell mass. Whilst the molecular mechanisms behind the adaptive
      programming of beta-cells are still poorly understood it is established that
      changes arising from maternal obesity and/or over-nutrition may affect the
      ability to maintain fetal beta-cell mass resulting in an increased risk of type 2
      diabetes in adulthood. 

PMID- 23882221
TI  - The sigma-1 receptor: a regulator of cancer cell electrical plasticity?
AB  - Originally mistaken as an opioid receptor, the sigma-1 receptor (Sig1R) is a
      ubiquitous membrane protein that has been involved in many cellular processes.
      While the precise function of Sig1R has long remained mysterious, recent studies
      have shed light on its role and the molecular mechanisms triggered. Sig1R is in
      fact a stress-activated chaperone mainly associated with the ER-mitochondria
      interface that can regulate cell survival through the control of calcium
      homeostasis. Sig1R functionally regulates ion channels belonging to various
      molecular families and it has thus been involved in neuronal plasticity and
      central nervous system diseases. Interestingly, Sig1R is frequently expressed in
      tumors but its function in cancer has not been yet clarified. In this review, we
      discuss the current understanding of Sig1R. We suggest herein that Sig1R shapes
      cancer cell electrical signature upon environmental conditions. Thus, Sig1R may
      be used as a novel therapeutic target to specifically abrogate pro-invasive
      functions of ion channels in cancer tissue. 

PMID- 23882224
TI  - Interactions between adenosine, angiotensin II and nitric oxide on the afferent
      arteriole influence sensitivity of the tubuloglomerular feedback.
AB  - Adenosine, via activation of A1 receptors on the afferent arteriole (AA),
      mediates the tubuloglomerular feedback (TGF) mechanism. Angiotensin II and nitric
      oxide (NO) can modulate the sensitivity of the TGF mechanism. However, the
      interaction among these substances in regulating the TGF resetting phenomenon has
      been debated. Studies in isolated perfused AA have shown a biphasic response to
      accumulating doses of adenosine alone. In the nanomolar range adenosine has a
      weak contractile effect (7%), whereas vasodilatation is observed at high
      concentrations. However, a synergistic interaction between the contractile
      response by adenosine and that of angiotensin II has been demonstrated. Adenosine
      in low concentrations strongly enhances the response to angiotensin II. At the
      same time, angiotensin II in physiological concentrations increases significantly
      the contractile response to adenosine. Moreover, addition of a NO donor (spermine
      NONOate) to increase NO bioavailability abolished the contractile response from
      combined application of angiotensin II and adenosine. These mutual modulating
      effects of adenosine and angiotensin II, and the effect of NO on the response of
      AA can contribute to the resetting of the TGF sensitivity. 

PMID- 23882222
TI  - Expanding functional repertoires of fungal peroxisomes: contribution to growth
      and survival processes.
AB  - It has long been regarded that the primary function of fungal peroxisomes is
      limited to the beta-oxidation of fatty acids, as mutants lacking peroxisomal
      function fail to grow in minimal medium containing fatty acids as the sole carbon
      source. However, studies in filamentous fungi have revealed that peroxisomes have
      diverse functional repertoires. This review describes the essential roles of
      peroxisomes in the growth and survival processes of filamentous fungi. One such
      survival mechanism involves the Woronin body, a Pezizomycotina-specific organelle
      that plugs the septal pore upon hyphal lysis to prevent excessive cytoplasmic
      loss. A number of reports have demonstrated that Woronin bodies are derived from
      peroxisomes. Specifically, the Woronin body protein Hex1 is targeted to
      peroxisomes by peroxisomal targeting sequence 1 (PTS1) and forms a self-assembled
      structure that buds from peroxisomes to form the Woronin body. Peroxisomal
      deficiency reduces the ability of filamentous fungi to prevent excessive
      cytoplasmic loss upon hyphal lysis, indicating that peroxisomes contribute to the
      survival of these multicellular organisms. Peroxisomes were also recently found
      to play a vital role in the biosynthesis of biotin, which is an essential
      cofactor for various carboxylation and decarboxylation reactions. In biotin
      prototrophic fungi, peroxisome-deficient mutants exhibit growth defects when
      grown on glucose as a carbon source due to biotin auxotrophy. The biotin
      biosynthetic enzyme BioF (7-keto-8-aminopelargonic acid synthase) contains a PTS1
      motif that is required for both peroxisomal targeting and biotin biosynthesis. In
      plants, the BioF protein contains a conserved PTS1 motif and is also localized in
      peroxisomes. These findings indicate that the involvement of peroxisomes in
      biotin biosynthesis is evolutionarily conserved between fungi and plants, and
      that peroxisomes play a key role in fungal growth. 

PMID- 23882225
TI  - The neuronal membrane as a key factor in neurodegeneration.

PMID- 23882223
TI  - Membrane potential and cancer progression.
AB  - Membrane potential (Vm ), the voltage across the plasma membrane, arises because
      of the presence of different ion channels/transporters with specific ion
      selectivity and permeability. Vm is a key biophysical signal in non-excitable
      cells, modulating important cellular activities, such as proliferation and
      differentiation. Therefore, the multiplicities of various ion
      channels/transporters expressed on different cells are finely tuned in order to
      regulate the Vm . It is well-established that cancer cells possess distinct
      bioelectrical properties. Notably, electrophysiological analyses in many cancer
      cell types have revealed a depolarized Vm that favors cell proliferation. Ion
      channels/transporters control cell volume and migration, and emerging data also
      suggest that the level of Vm has functional roles in cancer cell migration. In
      addition, hyperpolarization is necessary for stem cell differentiation. For
      example, both osteogenesis and adipogenesis are hindered in human mesenchymal
      stem cells (hMSCs) under depolarizing conditions. Therefore, in the context of
      cancer, membrane depolarization might be important for the emergence and
      maintenance of cancer stem cells (CSCs), giving rise to sustained tumor growth.
      This review aims to provide a broad understanding of the Vm as a bioelectrical
      signal in cancer cells by examining several key types of ion channels that
      contribute to its regulation. The mechanisms by which Vm regulates cancer cell
      proliferation, migration, and differentiation will be discussed. In the long
      term, Vm might be a valuable clinical marker for tumor detection with prognostic
      value, and could even be artificially modified in order to inhibit tumor growth
      and metastasis. 

PMID- 23882226
TI  - The noseleaf of Rhinolophus formosae focuses the Frequency Modulated (FM)
      component of the calls.
AB  - Bats of the family Rhinolophidae emit their echolocation calls through their
      nostrils and feature elaborate noseleaves shaping the directionality of the
      emissions. The calls of these bats consist of a long constant-frequency component
      preceded and/or followed by short frequency-modulated sweeps. While Rhinolophidae
      are known for their physiological specializations for processing the constant
      frequency part of the calls, previous evidence suggests that the noseleaves of
      these animals are tuned to the frequencies in the frequency modulated components
      of the calls. In this paper, we seek further support for this hypothesis by
      simulating the emission beam pattern of the bat Rhinolophus formosae. Filling the
      furrows of lancet and removing the basal lappets (i.e., two flaps on the
      noseleaf) we find that these conspicuous features of the noseleaf focus the
      emitted energy mostly for frequencies in the frequency-modulated components.
      Based on the assumption that this component of the call is used by the bats for
      ranging, we develop a qualitative model to assess the increase in performance due
      to the furrows and/or the lappets. The model confirms that both structures
      decrease the ambiguity in selecting relevant targets for ranging. The lappets and
      the furrows shape the emission beam for different spatial regions and frequency
      ranges. Therefore, we conclude that the presented evidence is in line with the
      hypothesis that different parts of the noseleaves of Rhinolophidae are tuned to
      different frequency ranges with at least some of the most conspicuous ones being
      tuned to the frequency modulated components of the calls-thus yielding strong
      evidence for the sensory importance of the component. 

PMID- 23882227
TI  - All inequality is not equal: children correct inequalities using resource value.
AB  - Fairness concerns guide children's judgments about how to share resources with
      others. However, it is unclear from past research if children take extant
      inequalities or the value of resources involved in an inequality into account
      when sharing with others; these questions are the focus of the current studies.
      In all experiments, children saw an inequality between two recipients-one had two
      more resources than another. What varied between conditions was the value of the
      resources that the child could subsequently distribute. When the resources were
      equal in value to those involved in the original inequality, children corrected
      the previous inequality by giving two resources to the child with fewer resources
      (Experiment 1). However, as the value of the resources increased relative to
      those initially shared by the experimenter, children were more likely to
      distribute the two high value resources equally between the two recipients,
      presumably to minimize the overall inequality in value (Experiments 1 and 2). We
      found that children specifically use value, not just size, when trying to
      equalize outcomes (Experiment 3) and further found that children focus on the
      relative rather than absolute value of the resources they share-when the
      experimenter had unequally distributed the same high value resource that the
      child would later share, children corrected the previous inequality by giving two
      high value resources to the person who had received fewer high value resources.
      These results illustrate that children attempt to correct past inequalities and
      try to maintain equality not just in the count of resources but also by using the
      value of resources. 

PMID- 23882228
TI  - Noise as a mechanism of anomalous face processing among persons with
      Schizophrenia.
AB  - There is substantial evidence that people with Schizophrenia (SCZ) have altered
      visual perception and cognition, including impaired face processing. However, the
      mechanism(s) underlying this observation are not yet known. Eye movement studies
      have found that people with SCZ do not direct their gaze to the most informative
      regions of the face (e.g., the eyes). This suggests that SCZ patients may be less
      able to extract the most relevant face information and therefore have decreased
      calculation efficiency. In addition, research with non-face stimuli indicates
      that SCZ is associated with increased levels of internal noise. Importantly, both
      calculation efficiency and internal noise have been shown to underpin face
      perception among healthy observers. Therefore, the current study applies noise
      masking to upright and inverted faces to determine if face processing deficits
      among those with SCZ are the result of changes in calculation efficiency,
      internal noise, or both. Consistent with previous results, SCZ participants
      exhibited higher contrast thresholds in order to identify masked target faces.
      However, higher thresholds were associated with increases in internal noise but
      unrelated to changes in calculation efficiency. These results suggest that SCZ
      related face processing deficits are the result of a decreased noise-to-signal
      ratio. The source of increased processing noise among these patients is unclear,
      but may emanate from abnormal neural dynamics. 

PMID- 23882229
TI  - Individual differences in adult handwritten spelling-to-dictation.
AB  - We report an investigation of individual differences in handwriting latencies and
      number of errors in a spelling-to-dictation task. Eighty adult participants wrote
      a list of 164 spoken words (presented in two sessions). The participants were
      also evaluated on a vocabulary test (Deltour, 1993). Various multiple regression
      analyses were performed (on both writing latency and errors). The analysis of the
      item means showed that the reliable predictors of spelling latencies were
      acoustic duration, cumulative word frequency, phonology-to-orthographic (PO)
      consistency, the number of letters in the word and the interaction between
      cumulative word frequency, PO consistency and imageability. (Error rates were
      also predicted by frequency, consistency, length and the interaction between
      cumulative word frequency, PO consistency and imageability.) The analysis of the
      participant means (and trials) showed that (1) there was both within- and between
      session reliability across the sets of items, (2) there was no trade-off between
      the utilization of lexical and non-lexical information, and (3) participants with
      high vocabulary knowledge were more accurate (and somewhat faster), and had a
      differential sensitivity to certain stimulus characteristics, than those with low
      vocabulary knowledge. We discuss the implications of these findings for theories
      of orthographic word production. 

PMID- 23882230
TI  - Scalar implicatures: working memory and a comparison with only.
AB  - A Scalar Implicature (SI) arises when the use of a relatively weak sentence
      (e.g., some politicians are corrupt) implies the denial of an alternative,
      stronger sentence (e.g., not all politicians are corrupt). The cognitive effort
      associated with the processing of SIs involves central memory resources (De Neys
      and Schaeken, 2007; Dieussaert et al., 2011; Marty et al., 2013). The goal of
      this study is to locate this previous result within the current psycholinguistic
      debate, and to understand at which level of SI processing these resources are
      specifically involved. Using a dual-task approach, we show that (1) tapping
      participant's memory resources interferes with the derivation of SIs, whereas (2)
      it does not affect the interpretation of sentences involving similar competition
      mechanisms between a sentence and potential alternatives through the use of only
      (e.g., only some politicians are corrupt). We explain how these findings suggest
      that the central memory resources are not involved in the core process at the
      source of SIs, and discuss how this difference between SIs and only bears on
      recent linguistic debates on the division of labor between grammar and
      pragmatics. 

PMID- 23882231
TI  - General and specific consciousness: a first-order representationalist approach.
AB  - It is widely acknowledged that a complete theory of consciousness should explain
      general consciousness (what makes a state conscious at all) and specific
      consciousness (what gives a conscious state its particular phenomenal quality).
      We defend first-order representationalism, which argues that consciousness
      consists of sensory representations directly available to the subject for action
      selection, belief formation, planning, etc. We provide a neuroscientific
      framework for this primarily philosophical theory, according to which neural
      correlates of general consciousness include prefrontal cortex, posterior parietal
      cortex, and non-specific thalamic nuclei, while neural correlates of specific
      consciousness include sensory cortex and specific thalamic nuclei. We suggest
      that recent data support first-order representationalism over biological theory,
      higher-order representationalism, recurrent processing theory, information
      integration theory, and global workspace theory. 

PMID- 23882232
TI  - Brain basis of self: self-organization and lessons from dreaming.
AB  - Through dreaming, a different facet of the self is created as a result of a self
      organizing process in the brain. Self-organization in biological systems often
      happens as an answer to an environmental change for which the existing system
      cannot cope; self-organization creates a system that can cope in the newly
      changed environment. In dreaming, self-organization serves the function of
      organizing disparate memories into a dream since the dreamer herself is not able
      to control how individual memories become weaved into a dream. The self-organized
      dream provides, thereby, a wide repertoire of experiences; this expanded
      repertoire of experience results in an expansion of the self beyond that
      obtainable when awake. Since expression of the self is associated with activity
      in specific areas of the brain, the article also discusses the brain basis of the
      self by reviewing studies of brain injured patients, discussing brain imaging
      studies in normal brain functioning when focused, when daydreaming and when
      asleep and dreaming. 

PMID- 23882233
TI  - Music, emotion, and time perception: the influence of subjective emotional
      valence and arousal?
AB  - The present study used a temporal bisection task with short (<2 s) and long (>2
      s) stimulus durations to investigate the effect on time estimation of several
      musical parameters associated with emotional changes in affective valence and
      arousal. In order to manipulate the positive and negative valence of music,
      Experiments 1 and 2 contrasted the effect of musical structure with pieces played
      normally and backwards, which were judged to be pleasant and unpleasant,
      respectively. This effect of valence was combined with a subjective arousal
      effect by changing the tempo of the musical pieces (fast vs. slow) (Experiment 1)
      or their instrumentation (orchestral vs. piano pieces). The musical pieces were
      indeed judged more arousing with a fast than with a slow tempo and with an
      orchestral than with a piano timbre. In Experiment 3, affective valence was also
      tested by contrasting the effect of tonal (pleasant) vs. atonal (unpleasant)
      versions of the same musical pieces. The results showed that the effect of tempo
      in music, associated with a subjective arousal effect, was the major factor that
      produced time distortions with time being judged longer for fast than for slow
      tempi. When the tempo was held constant, no significant effect of timbre on the
      time judgment was found although the orchestral music was judged to be more
      arousing than the piano music. Nevertheless, emotional valence did modulate the
      tempo effect on time perception, the pleasant music being judged shorter than the
      unpleasant music. 

PMID- 23882234
TI  - Brain response to prosodic boundary cues depends on boundary position.
AB  - Prosodic information is crucial for spoken language comprehension and especially
      for syntactic parsing, because prosodic cues guide the hearer's syntactic
      analysis. The time course and mechanisms of this interplay of prosody and syntax
      are not yet well-understood. In particular, there is an ongoing debate whether
      local prosodic cues are taken into account automatically or whether they are
      processed in relation to the global prosodic context in which they appear. The
      present study explores whether the perception of a prosodic boundary is affected
      by its position within an utterance. In an event-related potential (ERP) study we
      tested if the brain response evoked by the prosodic boundary differs when the
      boundary occurs early in a list of three names connected by conjunctions (i.e.,
      after the first name) as compared to later in the utterance (i.e., after the
      second name). A closure positive shift (CPS)-marking the processing of a prosodic
      phrase boundary-was elicited for stimuli with a late boundary, but not for
      stimuli with an early boundary. This result is further evidence for an immediate
      integration of prosodic information into the parsing of an utterance. In
      addition, it shows that the processing of prosodic boundary cues depends on the
      previously processed information from the preceding prosodic context. 

PMID- 23882235
TI  - Conspiracy theories as quasi-religious mentality: an integrated account from
      cognitive science, social representations theory, and frame theory.
AB  - Conspiracy theories (CTs) can take many forms and vary widely in popularity, the
      intensity with which they are believed and their effects on individual and
      collective behavior. An integrated account of CTs thus needs to explain how they
      come to appeal to potential believers, how they spread from one person to the
      next via communication, and how they motivate collective action. We summarize
      these aspects under the labels of stick, spread, and action. We propose the quasi
      religious hypothesis for CTs: drawing on cognitive science of religion, social
      representations theory, and frame theory. We use cognitive science of religion to
      describe the main features of the content of CTs that explain how they come to
      stick: CTs are quasi-religious representations in that their contents, forms and
      functions parallel those found in beliefs of institutionalized religions.
      However, CTs are quasi-religious in that CTs and the communities that support
      them, lack many of the institutional features of organized religions. We use
      social representations theory to explain how CTs spread as devices for making
      sense of sudden events that threaten existing worldviews. CTs allow laypersons to
      interpret such events by relating them to common sense, thereby defusing some of
      the anxiety that those events generate. We use frame theory to explain how some,
      but not all CTs mobilize collective counter-conspiratorial action by identifying
      a target and by proposing credible and concrete rationales for action. We specify
      our integrated account in 13 propositions. 

PMID- 23882236
TI  - Phenomenology of future-oriented mind-wandering episodes.
AB  - Recent research suggests that prospective and non-prospective forms of mind
      wandering possess distinct properties, yet little is known about what exactly
      differentiates between future-oriented and non-future-oriented mind-wandering
      episodes. In the present study, we used multilevel exploratory factor analyses
      (MEFA) to examine the factorial structure of various phenomenological dimensions
      of mind-wandering, and we then investigated whether future-oriented mind
      wandering episodes differ from other classes of mind-wandering along the
      identified factors. We found that the phenomenological dimensions of mind
      wandering are structured in four factors: representational format (inner speech
      vs. visual imagery), personal relevance, realism/concreteness, and structuration.
      Prospective mind-wandering differed from non-prospective mind-wandering along
      each of these factors. Specifically, future-oriented mind-wandering episodes
      involved inner speech to a greater extent, were more personally relevant, more
      realistic/concrete, and more often part of structured sequences of thoughts.
      These results show that future-oriented mind-wandering possesses a unique
      phenomenological signature and provide new insights into how this particular form
      of mind-wandering may adaptively contribute to autobiographical planning. 

PMID- 23882237
TI  - Functional and structural brain modifications induced by oculomotor training in
      patients with age-related macular degeneration.
AB  - Patients with age-related macular degeneration (AMD) are reliant on their
      peripheral visual field. Oculomotor training can help them to find the best area
      on intact peripheral retina and to efficiently stabilize eccentric fixation. In
      this study, nine patients with AMD were trained over a period of 6 months using
      oculomotor training protocols to improve fixation stability. They were followed
      over an additional period of 6 months, where they completed an auditory memory
      training as a sham training. In this cross-over design five patients started with
      the sham training and four with the oculomotor training. Seven healthy age
      matched subjects, who did not take part in any training procedure, served as
      controls. During the 6 months of training the AMD subjects and the control group
      took part in three functional and structural magnetic resonance imaging (MRI)
      sessions to assess training-related changes in the brain function and structure.
      The sham-training phase was accompanied by two more fMRI measurements, resulting
      in five MRI sessions at intervals of 3 months for all participants. Despite
      substantial variability in the training effects, on average, AMD patients
      benefited from the training measurements as indexed by significant improvements
      in their fixation stability, visual acuity, and reading speed. The patients
      showed a significant positive correlation between brain activation changes and
      improvements in fixation stability in the visual cortex during training. These
      correlations were less pronounced on the long-term after training had ceased. We
      also found a significant increase in gray and white matter in the posterior
      cerebellum after training in the patient group. Our results show that functional
      and structural brain changes can be associated, at least on the short-term, with
      benefits of oculomotor and/or reading training in patients with central scotomata
      resulting from AMD. 

PMID- 23882238
TI  - The depressive situation.
AB  - From a naturalistic perspective on mental illness, depression is often described
      in terms of biological dysfunctions, while a normative perspective emphasizes the
      lived experience of depression as a harmful condition. The paper relates a
      conceptual analysis of "depressive situation" to an analysis of the lived
      experience of depression. As such, it predominantly aims to specify depression as
      a harmful condition in lights of normative perspective on mental disorder, but
      partially refers to empirical research, i.e., naturalistic perspective on
      depression, to exemplarily stress on the methodological merits and limits of
      relating phenomenological considerations closer to empirical research. The
      depressive situation is further specified with an examination of the evaluative
      dynamics by which individuals meaningfully relate to themselves, others and the
      world. These evaluative dynamics emerge out of the interplay of pre-reflective
      and reflective processes, which are significantly altered in depression. Such
      alterations of the evaluative structure are inextricably intertwined with
      significant distortions of practical sense in depression. From a phenomenological
      perspective, these distortions of practical sense show in characteristic
      experiences of evaluative incoherence and impairments of agency. Finally, this
      paper focuses on an examination of "evaluative incapacity," which has the
      integrative potential to capture a range of typical changes of meaningful
      relatedness that determine the depressive situation. 

PMID- 23882239
TI  - How few and far between? Examining the effects of probe rate on self-reported
      mind wandering.
AB  - We examined whether the temporal rate at which thought probes are presented
      affects the likelihood that people will report periods of mind wandering. To
      evaluate this possibility, we had participants complete a sustained-attention
      task (the Metronome Response Task; MRT) during which we intermittently presented
      thought probes. Critically, we varied the average time between probes (i.e.,
      probe rate) across participants, allowing us to examine the relation between
      probe rate and mind-wandering rate. We observed a positive relation between these
      variables, indicating that people are more likely to report mind wandering as the
      time between probes increases. We discuss the methodological implications of this
      finding in the context of the mind-wandering literature, and suggest that
      researchers include a range of probe rates in future work to provide more insight
      into this methodological issue. 

PMID- 23882240
TI  - Brain responses and looking behavior during audiovisual speech integration in
      infants predict auditory speech comprehension in the second year of life.
AB  - The use of visual cues during the processing of audiovisual (AV) speech is known
      to be less efficient in children and adults with language difficulties and
      difficulties are known to be more prevalent in children from low-income
      populations. In the present study, we followed an economically diverse group of
      thirty-seven infants longitudinally from 6-9 months to 14-16 months of age. We
      used eye-tracking to examine whether individual differences in visual attention
      during AV processing of speech in 6-9 month old infants, particularly when
      processing congruent and incongruent auditory and visual speech cues, might be
      indicative of their later language development. Twenty-two of these 6-9 month old
      infants also participated in an event-related potential (ERP) AV task within the
      same experimental session. Language development was then followed-up at the age
      of 14-16 months, using two measures of language development, the Preschool
      Language Scale and the Oxford Communicative Development Inventory. The results
      show that those infants who were less efficient in auditory speech processing at
      the age of 6-9 months had lower receptive language scores at 14-16 months. A
      correlational analysis revealed that the pattern of face scanning and ERP
      responses to audiovisually incongruent stimuli at 6-9 months were both
      significantly associated with language development at 14-16 months. These
      findings add to the understanding of individual differences in neural signatures
      of AV processing and associated looking behavior in infants. 

PMID- 23882241
TI  - Dissociating compatibility effects and distractor costs in the additional
      singleton paradigm.
AB  - The interpretation of identity compatibility effects associated with irrelevant
      items outside the nominal focus of attention has fueled much of the debate over
      early versus late selection and perceptual load theory. However, compatibility
      effects have also played a role in the debate over the extent to which the
      involuntary allocation of spatial attention (i.e., attentional capture) is
      completely stimulus-driven or whether it is contingent on top-down control
      settings. For example, in the context of the additional singleton paradigm,
      irrelevant color singletons have been found to produce not only an overall cost
      in search performance but also significant compatibility effects. This
      combination of search costs and compatibility effects has been taken as evidence
      that spatial attention is indeed allocated in a bottom-up fashion to the salient
      but irrelevant singletons. However, it is possible that compatibility effects in
      the additional singleton paradigm reflect parallel processing of identity
      associated with low perceptual load rather than an involuntary shift of spatial
      attention. In the present experiments, manipulations of load were incorporated
      into the traditional additional singleton paradigm. Under low-load conditions,
      both search costs and compatibility effects were obtained, replicating previous
      studies. Under high-load conditions, search costs were still present, but
      compatibility effects were eliminated. This dissociation suggests that the costs
      associated with irrelevant singletons may reflect filtering processes rather than
      the allocation of spatial attention. 

PMID- 23882242
TI  - An asymmetry of translational biological motion perception in schizophrenia.
AB  - BACKGROUND: Biological motion perception is served by a network of regions in the
      occipital, posterior temporal, and parietal lobe, overlapping areas of reduced
      cortical volume in schizophrenia. The atrophy in these regions is assumed to
      account for deficits in biological motion perception described in schizophrenia
      but it is unknown whether the asymmetry of atrophy found in previous studies has
      a perceptual correlate. Here we look for possible differences in sensitivity to
      leftward and rightward translation of point-light biological motion in data
      collected for a previous study and explore its underlying neurobiology using
      functional imaging. METHODS: n = 64 patients with schizophrenia and n = 64
      controls performed a task requiring the detection of leftward or rightward
      biological motion using a standard psychophysical staircase procedure. six
      control subjects took part in the functional imaging experiment. RESULTS: We
      found a deficit of leftward but not rightward biological motion (leftward
      biological motion % accuracy patients = 57.9% +/- 14.3; controls = 63.6% +/- 11.3
      p = 0.01; rightward biological motion patients = 62.7% +/- 12.4; controls = 64.1%
      +/- 11.7; p > 0.05). The deficit reflected differences in distribution of
      leftward and rightward accuracy bias in the two populations. Directional bias
      correlated with functional outcome as measured by the Role Functioning Scale in
      the patient group when co-varying for negative symptoms (r = -0.272, p = 0.016).
      Cortical regions with preferential activation for leftward or rightward
      translation were identified in both hemispheres suggesting the psychophysical
      findings could not be accounted for by selective atrophy or functional change in
      one hemisphere alone. CONCLUSION: The findings point to translational direction
      as a novel functional probe to help understand the underlying neural mechanisms
      of wider cognitive dysfunction in schizophrenia.

PMID- 23882243
TI  - Adaptation to implied tilt: extensive spatial extrapolation of orientation
      gradients.
AB  - To extract the global structure of an image, the visual system must integrate
      local orientation estimates across space. Progress is being made toward
      understanding this integration process, but very little is known about whether
      the presence of structure exerts a reciprocal influence on local orientation
      coding. We have previously shown that adaptation to patterns containing circular
      or radial structure induces tilt-aftereffects (TAEs), even in locations where the
      adapting pattern was occluded. These spatially "remote" TAEs have novel tuning
      properties and behave in a manner consistent with adaptation to the local
      orientation implied by the circular structure (but not physically present) at a
      given test location. Here, by manipulating the spatial distribution of local
      elements in noisy circular textures, we demonstrate that remote TAEs are driven
      by the extrapolation of orientation structure over remarkably large regions of
      visual space (more than 20 degrees ). We further show that these effects are not
      specific to adapting stimuli with polar orientation structure, but require a
      gradient of orientation change across space. Our results suggest that mechanisms
      of visual adaptation exploit orientation gradients to predict the local pattern
      content of unfilled regions of space. 

PMID- 23882244
TI  - Gender differences in school achievement: The role of self-regulation.
AB  - This study examined whether different aspects of self-regulation (i.e., emotion
      and behavior regulation) account for gender differences in German and mathematics
      achievement. Specifically, we investigated whether higher school achievement by
      girls in comparison to boys can be explained by self-regulation. German and
      mathematics achievement were assessed in a sample of 53 German fifth graders (19
      boys, 34 girls) using formal academic performance tests (i.e., reading, writing,
      mathematics) and teachers' ratings (i.e., grades in German and mathematics).
      Moreover, teachers rated children's behavior regulation using the Self-Control
      Scale (SCS-K-D). Children's self-reported strategies of emotion regulation were
      assessed with the Questionnaire for the Measurement of Stress and Coping in
      Children and Adolescents (SSKJ 3-8). Age and intelligence (CFT 20-R) were
      included as control variables. Analyses of mean differences showed that girls
      outperformed boys in German achievement and behavior regulation. Regression
      analyses, using a bootstrapping method, revealed that relations between gender
      and German achievement were mediated by behavior regulation. Furthermore, we
      found a suppression effect of behavior regulation on the relation between gender
      and mathematics achievement: boys' mathematics achievement was underestimated
      when the analyses did not control for behavior regulation. We discuss these
      results from a developmental perspective and within the theoretical framework of
      self-regulation and achievement. 

PMID- 23882245
TI  - Visual stimulus parameters seriously compromise the measurement of approximate
      number system acuity and comparative effects between adults and children.
AB  - It has been suggested that a simple non-symbolic magnitude comparison task is
      sufficient to measure the acuity of a putative Approximate Number System (ANS). A
      proposed measure of the ANS, the so-called "internal Weber fraction" (w), would
      provide a clear measure of ANS acuity. However, ANS studies have never presented
      adequate evidence that visual stimulus parameters did not compromise measurements
      of w to such extent that w is actually driven by visual instead of numerical
      processes. We therefore investigated this question by testing non-symbolic
      magnitude discrimination in seven-year-old children and adults. We
      manipulated/controlled visual parameters in a more stringent manner than usual.
      As a consequence of these controls, in some trials numerical cues correlated
      positively with number while in others they correlated negatively with number.
      This congruency effect strongly correlated with w, which means that congruency
      effects were probably driving effects in w. Consequently, in both adults and
      children congruency had a major impact on the fit of the model underlying the
      computation of w. Furthermore, children showed larger congruency effects than
      adults. This suggests that ANS tasks are seriously compromised by the visual
      stimulus parameters, which cannot be controlled. Hence, they are not pure
      measures of the ANS and some putative w or ratio effect differences between
      children and adults in previous ANS studies may be due to the differential
      influence of the visual stimulus parameters in children and adults. In addition,
      because the resolution of congruency effects relies on inhibitory (interference
      suppression) function, some previous ANS findings were probably influenced by the
      developmental state of inhibitory processes especially when comparing children
      with developmental dyscalculia and typically developing children. 

PMID- 23882246
TI  - Bee positive: the importance of electroreception in pollinator cognitive ecology.

PMID- 23882247
TI  - Songbirds and humans apply different strategies in a sound sequence
      discrimination task.
AB  - The abilities of animals and humans to extract rules from sound sequences have
      previously been compared using observation of spontaneous responses and
      conditioning techniques. However, the results were inconsistently interpreted
      across studies possibly due to methodological and/or species differences.
      Therefore, we examined the strategies for discrimination of sound sequences in
      Bengalese finches and humans using the same protocol. Birds were trained on a
      GO/NOGO task to discriminate between two categories of sound stimulus generated
      based on an "AAB" or "ABB" rule. The sound elements used were taken from a
      variety of male (M) and female (F) calls, such that the sequences could be
      represented as MMF and MFF. In test sessions, FFM and FMM sequences, which were
      never presented in the training sessions but conformed to the rule, were
      presented as probe stimuli. The results suggested two discriminative strategies
      were being applied: (1) memorizing sound patterns of either GO or NOGO stimuli
      and generating the appropriate responses for only those sounds; and (2) using the
      repeated element as a cue. There was no evidence that the birds successfully
      extracted the abstract rule (i.e., AAB and ABB); MMF-GO subjects did not produce
      a GO response for FFM and vice versa. Next we examined whether those strategies
      were also applicable for human participants on the same task. The results and
      questionnaires revealed that participants extracted the abstract rule, and most
      of them employed it to discriminate the sequences. This strategy was never
      observed in bird subjects, although some participants used strategies similar to
      the birds when responding to the probe stimuli. Our results showed that the human
      participants applied the abstract rule in the task even without instruction but
      Bengalese finches did not, thereby reconfirming that humans have to extract
      abstract rules from sound sequences that is distinct from non-human animals. 

PMID- 23882248
TI  - The effects of alerting signals in masked priming.
AB  - Alerting signals often serve to reduce temporal uncertainty by predicting the
      time of stimulus onset. The resulting response time benefits have often been
      explained by facilitated translation of stimulus codes into response codes on the
      basis of established stimulus-response (S-R) links. In paradigms of masked S-R
      priming alerting signals also modulate response activation processes triggered by
      subliminally presented prime stimuli. In the present study we tested whether
      facilitation of visuo-motor translation processes due to alerting signals
      critically depends on established S-R links. Alerting signals resulted in
      significantly enhanced masked priming effects for masked prime stimuli that
      included and that did not include established S-R links (i.e., target vs. novel
      primes). Yet, the alerting-priming interaction was more pronounced for target
      than for novel primes. These results suggest that effects of alerting signals on
      masked priming are especially evident when S-R links between prime and target
      exist. At the same time, an alerting-priming interaction also for novel primes
      suggests that alerting signals also facilitate stimulus-response translation
      processes when masked prime stimuli provide action-trigger conditions in terms of
      programmed S-R links. 

PMID- 23882249
TI  - Differences between visual hemifields in identifying rapidly presented target
      stimuli: letters and digits, faces, and shapes.
AB  - The right hemisphere has been shown to play a dominant role in processing of
      visuo-spatial information. Recently, this role has been studied in the two-stream
      rapid serial visual presentation task. In this task, two alphanumerical targets
      are embedded in left and right simultaneous streams of rapidly changing letters.
      The second target (T2) is identified better in the left than in the right visual
      field. This difference has been interpreted as advantage of the right hemisphere
      (RH). However, a disadvantage of the left hemisphere (LH) could not be excluded
      so far. The LH, specialized for processing of verbal stimuli, might be overloaded
      due to constant input of letters from both visual fields. In the present study,
      this overload hypothesis was tested by reducing demands on verbal processing
      (Experiment 1), and by overloading the RH with non-verbal stimuli: faces
      (Experiment 2) and irregular shapes (Experiment 3). The left visual field
      advantage proved to be largely independent from the level of verbal load and from
      stimulus type. Therefore, although not entirely disproving the overload
      hypothesis, these results suggest as the most parsimonious explanation this
      asymmetry reflects a RH advantage, presumably in perceptual and attentional
      processing, rather than a LH disadvantage caused by verbal overload. 

PMID- 23882250
TI  - The Sarrazin effect: the presence of absurd statements in conspiracy theories
      makes canonical information less plausible.
AB  - Reptile prime ministers and flying Nazi saucers-extreme and sometimes off-wall
      conclusion are typical ingredients of conspiracy theories. While individual
      differences are a common research topic concerning conspiracy theories, the role
      of extreme statements in the process of acquiring and passing on conspiratorial
      stories has not been regarded in an experimental design so far. We identified six
      morphological components of conspiracy theories empirically. On the basis of
      these content categories a set of narrative elements for a 9/11 story was
      compiled. These elements varied systematically in terms of conspiratorial
      allegation, i.e., they contained official statements concerning the events of
      9/11, statements alleging to a conspiracy limited in time and space as well as
      extreme statements indicating an all-encompassing cover-up. Using the method of
      narrative construction, 30 people were given a set of cards with these statements
      and asked to construct the course of events of 9/11 they deem most plausible.
      When extreme statements were present in the set, the resulting stories were more
      conspiratorial; the number of official statements included in the narrative
      dropped significantly, whereas the self-assessment of the story's plausibility
      did not differ between conditions. This indicates that blatant statements in a
      pool of information foster the synthesis of conspiracy theories on an individual
      level. By relating these findings to one of Germany's most successful (and
      controversial) non-fiction books, we refer to the real-world dangers of this
      effect. 

PMID- 23882251
TI  - Fixations on objects in natural scenes: dissociating importance from salience.
AB  - The relation of selective attention to understanding of natural scenes has been
      subject to intense behavioral research and computational modeling, and gaze is
      often used as a proxy for such attention. The probability of an image region to
      be fixated typically correlates with its contrast. However, this relation does
      not imply a causal role of contrast. Rather, contrast may relate to an object's
      "importance" for a scene, which in turn drives attention. Here we operationalize
      importance by the probability that an observer names the object as characteristic
      for a scene. We modify luminance contrast of either a frequently named
      ("common"/"important") or a rarely named ("rare"/"unimportant") object, track the
      observers' eye movements during scene viewing and ask them to provide keywords
      describing the scene immediately after. When no object is modified relative to
      the background, important objects draw more fixations than unimportant ones.
      Increases of contrast make an object more likely to be fixated, irrespective of
      whether it was important for the original scene, while decreases in contrast have
      little effect on fixations. Any contrast modification makes originally
      unimportant objects more important for the scene. Finally, important objects are
      fixated more centrally than unimportant objects, irrespective of contrast. Our
      data suggest a dissociation between object importance (relevance for the scene)
      and salience (relevance for attention). If an object obeys natural scene
      statistics, important objects are also salient. However, when natural scene
      statistics are violated, importance and salience are differentially affected.
      Object salience is modulated by the expectation about object properties (e.g.,
      formed by context or gist), and importance by the violation of such expectations.
      In addition, the dependence of fixated locations within an object on the object's
      importance suggests an analogy to the effects of word frequency on landing
      positions in reading. 

PMID- 23882252
TI  - On the autonomy of the concept of disease in psychiatry.
AB  - Does the reference to a mental realm in using the notion of mental disorder lead
      to a dilemma that consists in either implying a Cartesian account of the mind
      body relation or in the need to give up a notion of mental disorder in its own
      right? Many psychiatrists seem to believe that denying substance dualism requires
      a purely neurophysiological stance for explaining mental disorder. However, this
      conviction is based on a limited awareness of the philosophical debate on the
      mind-body problem. This article discusses the reasonableness of the concept of
      mental disorder in relation to reductionist and eliminativist strategies in the
      philosophy of mind. It is concluded that we need a psychological level of
      explanation that cannot be reduced to neurophysiological findings in order to
      make sense of mental disorder. 

PMID- 23882253
TI  - Overview: does language production shape language form and comprehension?

PMID- 23882254
TI  - Is DOPA-Responsive Hypokinesia Responsible for Bimanual Coordination Deficits in
      Parkinson's Disease?
AB  - Bradykinesia is a well-documented DOPA-responsive clinical feature of Parkinson's
      disease (PD). While amplitude deficits (hypokinesia) are a key component of this
      slowness, it is important to consider how dopamine influences both the amplitude
      (hypokinesia) and frequency components of bradykinesia when a bimanually
      coordinated movement is required. Based on the notion that the basal ganglia are
      associated with sensory deficits, the influence of dopaminergic replacement on
      sensory feedback conditions during bimanual coordination was also evaluated.
      Bimanual movements were examined in PD and healthy comparisons in an
      unconstrained three-dimensional coordination task. PD were tested "off"
      (overnight withdrawal of dopaminergic treatment) and "on" (peak dose of
      dopaminergic treatment), while the healthy group was evaluated for practice
      effects across two sessions. Required cycle frequency (increased within each
      trial from 0.75 to 2 Hz), type of visual feedback (no vision, normal vision, and
      augmented vision), and coordination pattern (symmetrical in-phase and non
      symmetrical anti-phase) were all manipulated. Overall, coordination (mean
      accuracy and standard deviation of relative phase) and amplitude deficits during
      bimanual coordination were confirmed in PD participants. In addition, significant
      correlations were identified between severity of motor symptoms as well as
      bradykinesia to greater coordination deficits (accuracy and stability) in PD
      "off" group. However, even though amplitude deficits (hypokinesia) improved with
      dopaminergic replacement, it did not improve bimanual coordination performance
      (accuracy or stability) in PD patients from "off" to "on." Interestingly, while
      coordination performance in both groups suffered in the augmented vision
      condition, the amplitude of the more affected limb of PD was notably influenced.
      It can be concluded that DOPA-responsive hypokinesia contributes to, but is not
      directly responsible for bimanual coordination impairments in PD. It is likely
      that bimanual coordination deficits in PD are caused by the combination of
      dopaminergic system dysfunction as well as other neural impairments that may be
      DOPA-resistant or related to non-dopaminergic pathways. 

PMID- 23882256
TI  - Evaluation of the objective posturo-locomotor-manual method in patients with
      parkinsonian syndromes.
AB  - Objective methods for quantifying patients' movement capacity would be useful in
      evaluating progression and interventions in neurodegenerative diseases. The
      Posturo-Locomotor-Manual (PLM) test is a standardized automated movement test
      developed to measure hypokinetic movements in patients with Parkinsonism. Our
      hypotheses were that the PLM movement time (MT) correlates with the Unified
      Parkinson's disease rating scale (UPDRS III) motor section, and that the
      components of the PLM test correlate with the corresponding constructed domains
      of UPDRS III. We also evaluated the coherence between the results of the two
      assessment methods after a test dose of levodopa (l-DOPA). We assessed motor
      function using the PLM method and UPDRS III in parallel, in the absence of
      medication and after administration of 200 mg l-DOPA, in 73 patients with
      moderate to advanced Parkinsonism: 47 with Parkinson's disease (PD), 17 with
      multiple system atrophy (MSA), and 9 with progressive supranuclear palsy (PSP).
      There was a fair correlation between the two assessment tools in the PD patients
      but not in the MSA or PSP patients. In the full dataset, there was a fair to good
      correlation between UPDRS III and the PLM MT. At group level, the UPDRS III l
      DOPA test differentiated PD from MSA/PSP, whereas the PLM l-DOPA test
      differentiated between all three diagnoses. 

PMID- 23882255
TI  - Formation and propagation of tau oligomeric seeds.
AB  - Tau misfolding and aggregation leads to the formation of neurofibrillary tangles
      (NFTs), which have long been considered one of the main pathological hallmarks
      for numerous neurodegenerative diseases known as tauopathies, including
      Alzheimer's Disease (AD) and Parkinson's Disease (PD). However, recent studies
      completed both in vitro and in vivo suggest that intermediate forms of tau, known
      as tau oligomers, between the monomeric form and NFTs are the true toxic species
      in disease and the best targets for anti-tau therapies. However, the exact
      mechanism by which the spread of pathology occurs is unknown. Evidence suggests
      that tau oligomers may act as templates for the misfolding of native tau, thereby
      seeding the spread of the toxic forms of the protein. Recently, researchers have
      reported the ability of tau oligomers to enter and exit cells, propagating from
      disease-affected regions to unaffected areas. While the mechanism by which the
      spreading of misfolded tau occurs has yet to be elucidated, there are a few
      different models which have been proposed, including cell membrane stress and
      pore-formation, endocytosis and exocytosis, and non-traditional secretion of
      protein not enclosed by a membrane. Coming to an understanding of how toxic tau
      species seed and spread through the brain will be crucial to finding effective
      treatments for neurodegenerative tauopathies. 

PMID- 23882257
TI  - Parkin- and PINK1-Dependent Mitophagy in Neurons: Will the Real Pathway Please
      Stand Up?
AB  - Parkinson's disease (PD) is characterized by massive degeneration of dopaminergic
      neurons in the substantia nigra. Whereas the majority of PD cases are sporadic,
      about 5-10% of cases are familial and associated with genetic factors. The loss
      of parkin or PINK1, two such factors, leads to an early onset form of PD.
      Importantly, recent studies have shown that parkin functions downstream of PINK1
      in a common genetic pathway affecting mitochondrial homeostasis. More precisely,
      parkin has been shown to mediate the autophagy of damaged mitochondria
      (mitophagy) in a PINK1-dependent manner. However, much of the work characterizing
      this pathway has been carried out in immortalized cell lines overexpressing high
      levels of parkin. In contrast, whether or how endogenous parkin and PINK1
      contribute to mitophagy in neurons is much less clear. Here we review recent work
      addressing the role of parkin/PINK1-dependent mitophagy in neurons. Clearly, it
      appears that mitophagy pathways differ spatially and kinetically in neurons and
      immortalized cells, and therefore might diverge in their ultimate outcome and
      function. While evidence suggests that parkin can translocate to mitochondria in
      neurons, the function and mechanism of mitophagy downstream of parkin recruitment
      in neurons remains to be clarified. Moreover, it is noteworthy that most work has
      focused on the downstream signaling events in parkin/PINK1 mitophagy, whereas the
      upstream signaling pathways remain comparatively poorly characterized.
      Identifying the upstream signaling mechanisms that trigger parkin/PINK1 mitophagy
      will help to explain the nature of the insults affecting mitochondrial function
      in PD, and a better understanding of these pathways in neurons will be the key in
      identifying new therapeutic targets in PD. 

PMID- 23882258
TI  - Characteristics of tau oligomers.
AB  - In Alzheimer disease (AD) and other tauopathies, microtubule-associated protein
      tau becomes hyperphosphorylated, undergoes conformational changes, aggregates,
      eventually becoming neurofibrillary tangles (NFTs). As accumulating evidence
      suggests that NFTs themselves may not be toxic, attention is now turning toward
      the role of intermediate tau oligomers in AD pathophysiology. Sarkosyl extraction
      is a standard protocol for investigating insoluble tau aggregates in brains.
      There is a growing consensus that sarkosyl-insoluble tau correlates with the
      pathological features of tauopathy. While sarkosyl-insoluble tau from tauopathy
      brains has been well characterized as a pool of filamentous tau, other dimers,
      multimers, and granules of tau are much less well understood. There are protocols
      for identifying these tau oligomers. In this mini review, we discuss the
      characteristics of tau oligomers isolated via different methods and materials. 

PMID- 23882259
TI  - Ghrelin receptors in non-Mammalian vertebrates.
AB  - The growth hormone secretagogue-receptor (GHS-R) was discovered in humans and
      pigs in 1996. The endogenous ligand, ghrelin, was discovered 3 years later, in
      1999, and our understanding of the physiological significance of the ghrelin
      system in vertebrates has grown steadily since then. Although the ghrelin system
      in non-mammalian vertebrates is a subject of great interest, protein sequence
      data for the receptor in non-mammalian vertebrates has been limited until
      recently, and related biological information has not been well organized. In this
      review, we summarize current information related to the ghrelin receptor in non
      mammalian vertebrates. 

PMID- 23882260
TI  - Production of hydrogen sulfide from d-cysteine and its therapeutic potential.
AB  - Accumulating evidence shows that H2S has physiological functions in various
      tissues and organs. It includes regulation of neuronal activity, vascular
      tension, a release of insulin, and protection of the heart, kidney, and brain
      from ischemic insult. H2S is produced by enzymes from l-cysteine; cystathionine
      beta-synthase, cystathionine gamma-lyase, and 3-mercaptopyruvate
      sulfurtransferase (3MST) along with cysteine aminotransferase. We recently
      discovered an additional pathway for the production of H2S from d-cysteine. d
      Amino acid oxidase provides 3-mercaptopyruvate for 3MST to produce H2S. d
      Cysteine protects cerebellar neurons from oxidative stress and attenuates
      ischemia-reperfusion injury caused in the kidney more effectively than l
      cysteine. This review focuses on a novel pathway for the production of H2S and
      its therapeutic application especially to the renal diseases. 

PMID- 23882262
TI  - Review: elimination of bacteriophages in whey and whey products.
AB  - As the cheese market faces strong international competition, the optimization of
      production processes becomes more important for the economic success of dairy
      companies. In dairy productions, whey from former cheese batches is frequently re
      used to increase the yield, to improve the texture and to increase the nutrient
      value of the final product. Recycling of whey cream and particulated whey
      proteins is also routinely performed. Most bacteriophages, however, survive
      pasteurization and may re-enter the cheese manufacturing process. There is a risk
      that phages multiply to high numbers during the production. Contamination of whey
      samples with bacteriophages may cause problems in cheese factories because whey
      separation often leads to aerosol-borne phages and thus contamination of the
      factory environment. Furthermore, whey cream or whey proteins used for recycling
      into cheese matrices may contain thermo-resistant phages. Drained cheese whey can
      be contaminated with phages as high as 10(9) phages mL(-1). When whey batches are
      concentrated, phage titers can increase significantly by a factor of 10 hindering
      a complete elimination of phages. To eliminate the risk of fermentation failure
      during recycling of whey, whey treatments assuring an efficient reduction of
      phages are indispensable. This review focuses on inactivation of phages in whey
      by thermal treatment, ultraviolet (UV) light irradiation, and membrane
      filtration. Inactivation by heat is the most common procedure. However,
      application of heat for inactivation of thermo-resistant phages in whey is
      restricted due to negative effects on the functional properties of native whey
      proteins. Therefore an alternative strategy applying combined treatments should
      be favored - rather than heating the dairy product at extreme temperature/time
      combinations. By using membrane filtration or UV treatment in combination with
      thermal treatment, phage numbers in whey can be reduced sufficiently to prevent
      subsequent phage accumulations. 

PMID- 23882261
TI  - Ontogenesis of gonadotropin-releasing hormone neurons: a model for hypothalamic
      neuroendocrine cell development.
AB  - The vertebrate hypothalamo-pituitary-gonadal axis is the anatomical framework
      responsible for reproductive competence and species propagation. Essential to the
      coordinated actions of this three-tiered biological system is the fact that the
      regulatory inputs ultimately converge on the gonadotropin-releasing hormone
      (GnRH) neuronal system, which in rodents primarily resides in the
      preoptic/hypothalamic region. In this short review we will focus on: (1) the
      general embryonic temporal and spatial development of the rodent GnRH neuronal
      system, (2) the origin(s) of GnRH neurons, and (3) which transcription - and
      growth factors have been found to be critical for GnRH neuronal ontogenesis and
      cellular fate-specification. Moreover, we ask the question whether the molecular
      and cellular mechanisms involved in GnRH neuronal development may also play a
      role in the development of other hypophyseal secreting neuroendocrine cells in
      the hypothalamus. 

PMID- 23882263
TI  - Analysis of global gene expression changes in human bronchial epithelial cells
      exposed to spores of the allergenic fungus, Alternaria alternata.
AB  - Exposure and sensitivity to ubiquitous airborne fungi such as Alternaria
      alternata have long been implicated in the development, onset, and exacerbation
      of chronic allergic airway disorders. This present study is the first to
      investigate global changes in host gene expression during the interaction of
      cultured human bronchial epithelial cells and live Alternaria spores. In in vitro
      experiments human bronchial epithelial cells (BEAS-2B) were exposed to spores or
      media alone for 24 h. RNA was collected from three biological replicates per
      treatment and was used to assess changes in gene expression patterns using
      Affymetrix Human Genome U133 Plus 2.0 Arrays. In cells treated with Alternaria
      spores compared to controls, 613 probe sets representing 460 individual genes
      were found differentially expressed (p <= 0.05). In this set of 460 statistically
      significant, differentially expressed genes, 397 genes were found to be up
      regulated and 63 were down-regulated. Of these 397 up-regulated genes, 156 genes
      were found to be up-regulated >=2 fold. Interestingly, none of the 63 down
      regulated genes were found differentially expressed at <=-2 fold. Differentially
      expressed genes were identified following statistical analysis and subsequently
      used for pathway and network evaluation. Interestingly, many cytokine and
      chemokine immune response genes were up-regulated with a particular emphasis on
      interferon-inducible genes. Genes involved in cell death, retinoic acid
      signaling, and TLR3 response pathways were also significantly up-regulated. Many
      of the differentially up-regulated genes have been shown in other systems to be
      associated with innate immunity, inflammation and/or allergic airway diseases.
      This study now provides substantial information for further investigating
      specific genes and innate immune system pathways activated by Alternaria in the
      context of allergic airway diseases. 

PMID- 23882264
TI  - Antibiotic resistance in probiotic bacteria.
AB  - Probiotics are live microorganisms which when administered in adequate amounts
      confer a health benefit on the host. The main probiotic bacteria are strains
      belonging to the genera Lactobacillus and Bifidobacterium, although other
      representatives, such as Bacillus or Escherichia coli strains, have also been
      used. Lactobacillus and Bifidobacterium are two common inhabitants of the human
      intestinal microbiota. Also, some species are used in food fermentation processes
      as starters, or as adjunct cultures in the food industry. With some exceptions,
      antibiotic resistance in these beneficial microbes does not constitute a safety
      concern in itself, when mutations or intrinsic resistance mechanisms are
      responsible for the resistance phenotype. In fact, some probiotic strains with
      intrinsic antibiotic resistance could be useful for restoring the gut microbiota
      after antibiotic treatment. However, specific antibiotic resistance determinants
      carried on mobile genetic elements, such as tetracycline resistance genes, are
      often detected in the typical probiotic genera, and constitute a reservoir of
      resistance for potential food or gut pathogens, thus representing a serious
      safety issue. 

PMID- 23882265
TI  - Characterization of a MexAB-OprM efflux system necessary for productive
      metabolism of Pseudomonas azelaica HBP1 on 2-hydroxybiphenyl.
AB  - Pseudomonas azelaica HBP1 is one of the few bacteria known to completely
      mineralize the biocide and toxic compound 2-hydroxybiphenyl (2-HBP), but the
      mechanisms of its tolerance to the toxicity are unknown. By transposon mutant
      analysis and screening for absence of growth on water saturating concentrations
      of 2-HBP (2.7 mM) we preferentially found insertions in three genes with high
      homology to the mexA, mexB, and oprM efflux system. Mutants could grow at 2-HBP
      concentrations below 100 MUM but at lower growth rates than the wild-type.
      Exposure of the wild-type to increasing 2-HBP concentrations resulted in acute
      cell growth arrest and loss of membrane potential, to which the cells adapt after
      a few hours. By using ethidium bromide (EB) as proxy we could show that the
      mutants are unable to expel EB effectively. Inclusion of a 2-HBP reporter plasmid
      revealed that the wild-type combines efflux with metabolism at all 2-HBP
      concentrations, whereas the mutants cannot remove the compound and arrest
      metabolism at concentrations above 24 MUM. The analysis thus showed the
      importance of the MexAB-OprM system for productive metabolism of 2-HBP. 

PMID- 23882266
TI  - The C-Type Lectin Receptor SIGNR3 Binds to Fungi Present in Commensal Microbiota
      and Influences Immune Regulation in Experimental Colitis.
AB  - Inflammatory bowel disease is a condition of acute and chronic inflammation of
      the gut. An important factor contributing to pathogenesis is a dysregulated
      mucosal immunity against commensal bacteria and fungi. Host pattern-recognition
      receptors (PRRs) sense commensals in the gut and are involved in maintaining the
      balance between controlled responses to pathogens and overwhelming innate immune
      activation. C-type lectin receptors (CLRs) are PRRs recognizing glycan structures
      on pathogens and self-antigens. Here we examined the role of the murine CLR
      specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related
      3 (SIGNR3) in the recognition of commensals and its involvement in intestinal
      immunity. SIGNR3 is the closest murine homolog of the human dendritic cell
      specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)
      receptor recognizing similar carbohydrate ligands such as terminal fucose or high
      mannose glycans. We discovered that SIGNR3 recognizes fungi present in the
      commensal microbiota. To analyze whether this interaction impacts the intestinal
      immunity against microbiota, the dextran sulfate sodium-induced colitis model was
      employed. SIGNR3(-/-) mice exhibited an increased weight loss associated with
      more severe colitis symptoms compared to wild-type control mice. The increased
      inflammation in SIGNR3(-/-) mice was accompanied by a higher level of TNF-alpha
      in colon. Our findings demonstrate for the first time that SIGNR3 recognizes
      intestinal fungi and has an immune regulatory role in colitis. 

PMID- 23882267
TI  - The nature of activatory and tolerogenic dendritic cell-derived signal 2.

PMID- 23882268
TI  - Antibodies and their receptors: different potential roles in mucosal defense.
AB  - Over recent years it has become increasingly apparent that mucosal antibodies are
      not only restricted to the IgM and IgA isotypes, but that also other isotypes and
      particularly IgG can be found in significant quantities at some mucosal surfaces,
      such as in the genital tract. Their role is more complex than traditionally
      believed with, among other things, the discovery of novel function of mucosal
      immunoglobulin receptors. A thorough knowledge in the source and function and
      mucosal immunoglobulins is particularly important in development of vaccines
      providing mucosal immunity, and also in the current climate of microbicide
      development, to combat major world health issues such as HIV. We present here a
      comprehensive review of human antibody mediated mucosal immunity. 

PMID- 23882269
TI  - Effects of Hypoxia on the Immunomodulatory Properties of Adipose Tissue-Derived
      Mesenchymal Stem cells.
AB  - Adipose tissue-derived mesenchymal stem cells (ASC) are of great interest as a
      cellular therapeutic agent for regenerative and immunomodulatory purposes. The
      function of ASC adapts to environmental conditions, such as oxygen tension.
      Oxygen levels within tissues are typically much lower than under standard culture
      conditions and ASC used for therapy therefore encounter a change from normoxic to
      hypoxic conditions. The effect of hypoxia on the regenerative potential of ASC
      has been investigated in a number of studies. The effect of hypoxia on the
      immunomodulatory function of ASC, however, remains to be determined. In the
      present study the effect of hypoxic (1% oxygen) culture conditions on human ASC
      was examined. ASC showed no signs of toxicity under low oxygen levels and no
      major immunophenotypical changes were observed, apart from a down regulation of
      the marker CD105. Oxygen tension had no effect on the proliferation of ASC and
      colony forming unit efficiency remained the same under 1 and 20% oxygen. Under
      both oxygen levels ASC were capable of strong upregulation of the
      immunomodulatory molecules indoleamine 2,3-dioxygenase (IDO) and programed death
      ligand-1 upon stimulation with IFN-gamma and TNF-alpha, and, in addition, IDO
      activity as measured by the accumulation of l-kynurenine was not affected under
      hypoxia. The ability of ASC to inhibit anti-CD3/CD28 stimulated CD4(+) and CD8(+)
      T cell proliferation was not hampered by hypoxia. The results of the present
      study demonstrate that the immunosuppressive capacity of ASC is maintained under
      hypoxic conditions. These findings are important for the therapeutic use of ASC
      and may be applied for the in vitro generation of ASC with improved functionality
      for therapeutic use. 

PMID- 23882271
TI  - Autophagy for Better or Worse during Infectious Diseases.

PMID- 23882270
TI  - Regulation of hematopoietic stem cell activity by inflammation.
AB  - Hematopoietic stem cells (HSCs) are quiescent cells with self-renewal capacity
      and the ability to generate all mature blood cells. HSCs normally reside in
      specialized niches in the bone marrow that help maintain their quiescence and
      long-term repopulating activity. There is emerging evidence that certain
      cytokines induced during inflammation have significant effects on HSCs in the
      bone marrow. Type I and II interferons, tumor necrosis factor, and
      lipopolysaccharide (LPS) directly stimulate HSC proliferation and
      differentiation, thereby increasing the short-term output of mature effector
      leukocytes. However, chronic inflammatory cytokine signaling can lead to HSC
      exhaustion and may contribute the development of hematopoietic malignancies. Pro
      inflammatory cytokines such as G-CSF can also indirectly affect HSCs by altering
      the bone marrow microenvironment, disrupting the stem cell niche, and leading to
      HSC mobilization into the blood. Herein, we review our current understanding of
      the effects of inflammatory mediators on HSCs, and we discuss the potential
      clinical implications of these findings with respect to bone marrow failure and
      leukemogenesis. 

PMID- 23882272
TI  - Mutations in HISTONE ACETYLTRANSFERASE1 affect sugar response and gene expression
      in Arabidopsis.
AB  - Nutrient response networks are likely to have been among the first response
      networks to evolve, as the ability to sense and respond to the levels of
      available nutrients is critical for all organisms. Although several forward
      genetic screens have been successful in identifying components of plant sugar
      response networks, many components remain to be identified. Toward this end, a
      reverse genetic screen was conducted in Arabidopsis thaliana to identify
      additional components of sugar-response networks. This screen was based on the
      rationale that some of the genes involved in sugar-response networks are likely
      to be themselves sugar regulated at the steady-state mRNA level and to encode
      proteins with activities commonly associated with response networks. This
      rationale was validated by the identification of hac1 mutants that are defective
      in sugar response. HAC1 encodes a histone acetyltransferase. Histone
      acetyltransferases increase transcription of specific genes by acetylating
      histones associated with those genes. Mutations in HAC1 also cause reduced
      fertility, a moderate degree of resistance to paclobutrazol and altered
      transcript levels of specific genes. Previous research has shown that hac1
      mutants exhibit delayed flowering. The sugar-response and fertility defects of
      hac1 mutants may be partially explained by decreased expression of AtPV42a and
      AtPV42b, which are putative components of plant SnRK1 complexes. SnRK1 complexes
      have been shown to function as central regulators of plant nutrient and energy
      status. Involvement of a histone acetyltransferase in sugar response provides a
      possible mechanism whereby nutritional status could exert long-term effects on
      plant development and metabolism. 

PMID- 23882273
TI  - Multifunctional fructans and raffinose family oligosaccharides.
AB  - Fructans and raffinose family oligosaccharides (RFOs) are the two most important
      classes of water-soluble carbohydrates in plants. Recent progress is summarized
      on their metabolism (and regulation) and on their functions in plants and in food
      (prebiotics, antioxidants). Interest has shifted from the classic inulin-type
      fructans to more complex fructans. Similarly, alternative RFOs were discovered
      next to the classic RFOs. Considerable progress has been made in the
      understanding of structure-function relationships among different kinds of plant
      fructan metabolizing enzymes. This helps to understand their evolution from
      (invertase) ancestors, and the evolution and role of so-called "defective
      invertases." Both fructans and RFOs can act as reserve carbohydrates, membrane
      stabilizers and stress tolerance mediators. Fructan metabolism can also play a
      role in osmoregulation (e.g., flower opening) and source-sink relationships.
      Here, two novel emerging roles are highlighted. First, fructans and RFOs may
      contribute to overall cellular reactive oxygen species (ROS) homeostasis by
      specific ROS scavenging processes in the vicinity of organellar membranes (e.g.,
      vacuole, chloroplasts). Second, it is hypothesized that small fructans and RFOs
      act as phloem-mobile signaling compounds under stress. It is speculated that such
      underlying antioxidant and oligosaccharide signaling mechanisms contribute to
      disease prevention in plants as well as in animals and in humans. 

PMID- 23882274
TI  - A critical appraisal of phloem-mobile signals involved in tuber induction.
AB  - The identification of FLOWERING LOCUS T (FT) and several FT homologs as phloem
      mobile proteins that regulate flowering has sparked the search for additional
      homologs involved in the long-distance regulation of other developmental
      processes. Given that flowering and tuber induction share regulatory pathways,
      the quest for long-distance tuberization signals has been further stimulated.
      Several tuberization regulators have been proposed as mobile molecules, including
      the FT family protein StSP6A, the plant growth regulators gibberellins and the
      microRNA miR172. Although some of these hypotheses are attractive and plausible,
      evidence that these molecules are transmissible in potato has yet to be obtained.
      Two mRNAs encoding transcription factors, StBEL5 and POTATO HOMEOBOX 1 (POTH1),
      are mobile and correlate with tuber induction. However, evidence that StBEL5 or
      POTH1 are required for tuberization is not available yet. Therefore, there are
      several good candidates for long-distance molecules in the tuberization process.
      Further research should test their role as systemic tuberization signals. 

PMID- 23882275
TI  - Phloem-mobile messenger RNAs and root development.
AB  - Numerous signal molecules move through the phloem to regulate development,
      including proteins, secondary metabolites, small RNAs and full-length
      transcripts. Several full-length mRNAs have been identified that move long
      distances in a shootward or rootward direction through the plant vasculature to
      modulate both floral and vegetative processes of growth. Here we discuss two
      recently discovered examples of long-distance transport of full-length mRNAs into
      roots and the potential target genes and pathways for these mobile signals. In
      both cases, the mobile RNAs regulate root growth. Previously, RNA movement assays
      demonstrated that transcripts of StBEL5, a transcription factor from the three
      amino-loop-extension superclass, move through the phloem to stolon tips to
      enhance tuber formation in potato (Solanum tuberosum L.). StBEL5 mRNA originates
      in the leaf and its movement to stolons is induced by a short-day photoperiod.
      Movement of StBEL5 RNA to roots correlated with increased growth and the
      accumulation of several transcripts associated with hormone metabolism, including
      GA2-oxidase1, YUCCA1a and -c, several Aux/IAA types, and PIN1, -2, and -4 was
      observed. In another example, heterografting techniques were used to identify
      phloem-mobile Aux/IAA transcripts in Arabidopsis. Movement assays confirmed that
      these Aux/IAA transcripts are transported into the root system where they
      suppress lateral root formation. Phloem transport of both StBEL5 and Aux/IAA RNAs
      are linked to hormone metabolism and both target auxin synthesis genes or auxin
      signaling processes. The mechanisms of transport for these mobile RNAs, the
      impact they have on controlling root growth, and a potential transcriptional
      connection between the BEL1/KNOX complex and Aux/IAA genes are discussed. 

PMID- 23882276
TI  - Vascular gene expression: a hypothesis.
AB  - The phloem is the conduit through which photoassimilates are distributed from
      autotrophic to heterotrophic tissues and is involved in the distribution of
      signaling molecules that coordinate plant growth and responses to the
      environment. Phloem function depends on the coordinate expression of a large
      array of genes. We have previously identified conserved motifs in upstream
      regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap
      mRNAs, displaying expression in vascular tissues. This tissue-specific expression
      in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in
      gene promoters. In this work we have searched for common motifs in upstream
      regions of the homologous genes from plants considered to possess a "primitive"
      vascular tissue (a lycophyte), as well as from others that lack a true vascular
      tissue (a bryophyte), and finally from chlorophytes. Both lycophyte and bryophyte
      display motifs similar to those found in Arabidopsis with a significantly low E
      value, while the chlorophytes showed either a different conserved motif or no
      conserved motif at all. These results suggest that these same genes are expressed
      coordinately in non-vascular plants; this coordinate expression may have been one
      of the prerequisites for the development of conducting tissues in plants. We have
      also analyzed the phylogeny of conserved proteins that may be involved in phloem
      function and development. The presence of CmPP16, APL, FT, and YDA in
      chlorophytes suggests the recruitment of ancient regulatory networks for the
      development of the vascular tissue during evolution while OPS is a novel protein
      specific to vascular plants. 

PMID- 23882277
TI  - Metabolic engineering of raffinose-family oligosaccharides in the phloem reveals
      alterations in carbon partitioning and enhances resistance to green peach aphid.
AB  - Many plants employ energized loading strategies to accumulate osmotically-active
      solutes into the phloem of source organs to accentuate the hydrostatic pressure
      gradients that drive the flow of water, nutrients and signals from source to
      sinks. Proton-coupled symport of sugars from the apoplasm into the phloem
      symplasm is the best studied phloem-loading mechanism. As an alternative,
      numerous species use a polymer trapping mechanism to load through symplasm:
      sucrose enters the phloem through specialized plasmodesmata and is converted to
      raffinose-family oligosaccharides (RFOs) which accumulate because of their larger
      size. In this study, metabolic engineering was used to generate RFOs at the
      inception of the translocation stream of Arabidopsis thaliana, which loads from
      the apoplasm and transports predominantly sucrose, and the fate of the sugars
      throughout the plant determined. Three genes, GALACTINOL SYNTHASE, RAFFINOSE
      SYNTHASE and STACHYOSE SYNTHASE, were expressed from promoters specific to the
      companion cells of minor veins. Two transgenic lines homozygous for all three
      genes (GRS63 and GRS47) were selected for further analysis. Three-week-old plants
      of both lines had RFO levels approaching 50% of total soluble sugar. RFOs were
      also identified in exudates from excised leaves of transgenic plants whereas
      levels were negligible in exudates from wild type (WT) leaves. Differences in
      starch accumulation between WT and GRS63 and GRS47 lines were not observed.
      Similarly, there were no differences in vegetative growth between WT and
      engineered plants, but the latter flowered slightly earlier. Finally, since the
      sugar composition of the translocation stream appeared altered, we tested for an
      impact on green peach aphid (Myzus persicae Sulzer) feeding. When given a choice
      between WT and transgenic plants, green peach aphids preferred settling on the WT
      plants. Furthermore, green peach aphid fecundity was lower on the transgenic
      plants compared to the WT plants. When added to an artificial diet, RFOs did not
      have a negative effect on aphid fecundity, suggesting that although aphid
      resistance in the transgenic plants is enhanced, it is not due to direct toxicity
      of RFO toward the insect. 

PMID- 23882279
TI  - A new era of allele-specific diagnostics?

PMID- 23882278
TI  - Cigarette smoking and DNA methylation.
AB  - DNA methylation is the most studied epigenetic modification, capable of
      controlling gene expression in the contexts of normal traits or diseases. It is
      highly dynamic during early embryogenesis and remains relatively stable
      throughout life, and such patterns are intricately related to human development.
      DNA methylation is a quantitative trait determined by a complex interplay of
      genetic and environmental factors. Genetic variants at a specific locus can
      influence both regional and distant DNA methylation. The environment can have
      varying effects on DNA methylation depending on when the exposure occurs, such as
      during prenatal life or during adulthood. In particular, cigarette smoking in the
      context of both current smoking and prenatal exposure is a strong modifier of DNA
      methylation. Epigenome-wide association studies have uncovered candidate genes
      associated with cigarette smoking that have biologically relevant functions in
      the etiology of smoking-related diseases. As such, DNA methylation is a potential
      mechanistic link between current smoking and cancer, as well as prenatal
      cigarette-smoke exposure and the development of adult chronic diseases. 

PMID- 23882281
TI  - New hope for a microRNA therapy for pulmonary arterial hypertension.

PMID- 23882280
TI  - Highlighting the DNA damage response with ultrashort laser pulses in the near
      infrared and kinetic modeling.
AB  - Our understanding of the mechanisms governing the response to DNA damage in
      higher eucaryotes crucially depends on our ability to dissect the temporal and
      spatial organization of the cellular machinery responsible for maintaining
      genomic integrity. To achieve this goal, we need experimental tools to inflict
      DNA lesions with high spatial precision at pre-defined locations, and to
      visualize the ensuing reactions with adequate temporal resolution. Near-infrared
      femtosecond laser pulses focused through high-aperture objective lenses of
      advanced scanning microscopes offer the advantage of inducing DNA damage in a 3D
      confined volume of subnuclear dimensions. This high spatial resolution results
      from the highly non-linear nature of the excitation process. Here we review
      recent progress based on the increasing availability of widely tunable and user
      friendly technology of ultrafast lasers in the near infrared. We present a
      critical evaluation of this approach for DNA microdamage as compared to the
      currently prevalent use of UV or VIS laser irradiation, the latter in combination
      with photosensitizers. Current and future applications in the field of DNA repair
      and DNA-damage dependent chromatin dynamics are outlined. Finally, we discuss the
      requirement for proper simulation and quantitative modeling. We focus in
      particular on approaches to measure the effect of DNA damage on the mobility of
      nuclear proteins and consider the pros and cons of frequently used analysis
      models for FRAP and photoactivation and their applicability to non-linear
      photoperturbation experiments. 

PMID- 23882282
TI  - Do chromatin changes around a nascent double strand DNA break spread spherically
      into linearly non-adjacent chromatin?
AB  - In the last decade, a lot has been done in elucidating the sequence of events
      that occur at the nascent double strand DNA break. Nevertheless, the overall
      structure formed by the DNA damage response (DDR) factors around the break site,
      the repair focus, remains poorly understood. Although most of the data presented
      so far only address events that occur in chromatin in cis around the break, there
      are strong indications that in mammalian systems it may also occur in trans,
      analogous to the recent findings showing this if budding yeast. There have been
      attempts to address the issue but the final proof is still missing due to lack of
      a proper experimental system. If found to be true, the spatial distribution of
      DDR factors would have a major impact on the neighboring chromatin both in cis
      and in trans, significantly affecting local chromatin function; gene
      transcription and potentially other functions. 

PMID- 23882283
TI  - Familial hypercholesterolemia and the atherosclerotic disease.
AB  - Familial hypercholesterolemia (FH) is associated with premature atherosclerotic
      cardiovascular diseases, and is inherited as an autosomal dominant trait. The
      prevalence of heterozygous FH is one in five hundred people. Owing to
      dysfunctional low density lipoprotein (LDL) receptors due to genetic mutations,
      serum low density lipoprotein-cholesterol (LDL-C) levels are considerably
      increased from birth. FH is clinically diagnosed by confirmation of family
      history and characteristic findings such as tendon xanthoma or xanthelasma. Thus,
      clinical concern and suspicion are important for early diagnosis of the disease.
      Current guidelines recommend lowering LDL-C concentration to at least 50% from
      baseline. Statins are shown to lower LDL-C levels with high safety, and thus,
      have been the drug of choice. However, it is difficult to achieve an ideal level
      of LDL-C with a single statin therapy in the majority of FH patients.
      Alternatively, lipid lowering combination therapy with the recently-introduced
      ezetimibe has shown more encouraging results. 

PMID- 23882284
TI  - False Positive ST-Segment Elevation Myocardial Infarction.

PMID- 23882285
TI  - Etiologies and predictors of ST-segment elevation myocardial infarction.
AB  - BACKGROUND AND OBJECTIVES: Rapid diagnosis of ST-segment elevation myocardial
      infarction (STEMI) is essential for the appropriate management of patients. We
      investigated the prevalence, etiologies and predictors of false-positive
      diagnosis of STEMI and subsequent inappropriate catheterization laboratory
      activation in patients with presumptive diagnosis of STEMI. SUBJECTS AND METHODS:
      Four hundred fifty-five consecutive patients (62+/-13 years, 345 males) with
      presumptive diagnosis of STEMI between August 2008 and November 2010 were
      included. RESULTS: A false-positive diagnosis of STEMI was made in 34 patients
      (7.5%) with no indication of coronary artery lesion. Common causes for the false
      positive diagnosis were coronary spasm in 10 patients, left ventricular
      hypertrophy in 5 patients, myocarditis in 4 patients, early repolarization in 3
      patients, and previous myocardial infarction and stress-induced cardiomyopathy in
      2 patients each. In multivariate logistic regression analysis, symptom-to-door
      time >12 hours {odds ratio (OR) 4.995, 95% confidence interval (CI) 1.384-18.030,
      p=0.014}, presenting symptom other than chest pain (OR 7.709, 95% CI 1.255
      39.922, p=0.027), absence of Q wave (OR 9.082, CI 2.631-31.351, p<0.001) and
      absence of reciprocal changes on electrocardiography (ECG) (OR 17.987, CI 5.295
      61.106, p<0.001) were independent predictors of false-positive diagnosis of
      STEMI. CONCLUSION: In patients whom STEMI was planned for primary coronary
      intervention, the false-positive diagnosis of STEMI was not rare. Correct
      interpretation of ECGs and consideration of ST-segment elevation in conditions
      other than STEMI may reduce inappropriate catheterization laboratory activation.

PMID- 23882286
TI  - Impact of plaque composition on long-term clinical outcomes in patients with
      coronary artery occlusive disease.
AB  - BACKGROUND AND OBJECTIVES: It is unclear which plaque component is related with
      long-term clinical outcomes in patients with coronary artery occlusive disease
      (CAOD). We assessed the relationship between plaque compositions and long-term
      clinical outcomes in those patients. SUBJECTS AND METHODS: The study subjects
      consisted of 339 consecutive patients (mean 61.7+/-12.2 years old, 239 males) who
      underwent coronary angiogram and a virtual histology-intravascular ultrasound
      examination. Major adverse cardiac and cerebrovascular events (MACCE), including
      all-cause death, non-fatal myocardial infarction, cerebrovascular events, and
      target vessel revascularization were evaluated during a mean 28-month follow-up
      period. RESULTS: Patients with high fibrofatty volume (FFV, >8.90 mm(3), n=169)
      had a higher incidence of MACCE (25.4% vs. 14.7%, p=0.015), male sex (75.7% vs.
      65.3%, p=0.043), acute coronary syndrome (53.3% vs. 35.9%, p=0.002), multivessel
      disease (62.7% vs. 41.8%, p<0.001) and post-stent slow flow (10.7% vs. 2.4%,
      p=0.002) than those with low FFV (FFV<=8.90 mm(3), n=170). Other plaque
      composition factors such as fibrous area/volume, dense calcified area/volume, and
      necrotic core area/volume did not show any impact on MACCE. Cardiogenic shock
      {hazard ratio (HR)=8.44; 95% confidence interval (CI)=3.00-23.79; p<0.001} and
      FFV (HR=1.85; 95% CI=1.12-3.07; p=0.016) were the independent predictors of MACCE
      by Cox regression analysis. Thin-cap fibroatheroma, necrotic core area, and
      necrotic core volume were not associated with MACCE. CONCLUSION: FFV of a culprit
      lesion was associated with unfavorable long-term clinical outcomes in patients
      with CAOD.

PMID- 23882287
TI  - Assesment of myocardial ischemia by combination of tissue synchronisation imaging
      and dobutamine stress echocardiography.
AB  - BACKGROUND AND OBJECTIVES: Dobutamine stress echocardiography (DSE) is an
      important non-invasive imaging method for evaluating ischemia. However, wall
      motion interpretation can be impaired by the experience level of the interpreter
      and the subjectivity of the visual assessment. In our study we aimed to combine
      DSE and tissue syncronisation imaging to increase sensitivity for detecting
      ischemia. SUBJECTS AND METHODS: 50 patients with indications for DSE were
      included in the study. In 25 patients we found DSE positive for ischemia and in
      the other 25 patients we found it to be negative. The negative group was accepted
      as the control group. There was no significant difference in terms of risk
      factors and echocardiographic parameters between the two groups, except for wall
      motion scores. In both groups, left ventricular dyssychrony was accepted as the
      difference between time to peak systolic velocity (Ts) in the reciprocal four
      couple of non-apical segments at rest and during peak stress. Timings were
      corrected for heart rate. We compared the differences of the dyssynchronisation
      value at rest and during peak stress to determine the distinctions within the
      groups and between the groups of DSE positive and negative patients. RESULTS: We
      found that stress and ischemia did not create any significant difference over the
      left intraventricular dyssynchrony with DSE, although at the segmenter level it
      prolonged the time to peak systolic velocity (p<0.05). These alterations did not
      show any significant difference between positive and negative DSE groups.
      CONCLUSION: As a result, this segmenter dyssynchrony and the time to peak
      systolic velocity, which is corrected for heart rate, did not enhance any new
      value over DSE for detecting ischemia.

PMID- 23882288
TI  - Correlation between Proximal Abdominal Aortic Stiffness Measured by Ultrasound
      and Brachial-Ankle Pulse Wave Velocity.
AB  - BACKGROUND AND OBJECTIVES: The proximal portion of the abdominal aorta (AA) is
      characterized by minimal arteriosclerosis compared with other aortic segments. To
      assess the clinical usefulness of this characteristic, the correlation between
      ultrasonographically measured proximal AA stiffness and brachial-ankle pulse wave
      velocity (baPWV) was examined. SUBJECTS AND METHODS: 285 subjects were analyzed,
      half with hypertension and half with normal blood pressure. Proximal AA was
      examined using ultrasonography; strain, distensibility, elastic modulus, and the
      stiffness index were determined. After adjustment for age, gender, body mass
      index (BMI), systolic blood pressure (SBP), and heart rate, the relationships
      between baPWV and all these parameters were tested. RESULTS: The mean age of the
      study subjects was 58.1+/-12.8 years and the mean BMI was 24.3+/-3.8 kg/cm(2).
      58.9% of the subjects were female. 42.8% were hypertensive subjects. Among the
      hypertensive subjects, 56.0% were taking antihypertensive medication. Adjusted
      partial correlation coefficients for the relationship between baPWV with strain,
      distensibility, elastic modulus, and the stiffness index of the proximal AA were 
      0.203 (p=0.01), -0.121 (p=0.129), 0.304 (p=0.0001), and 0.299 (p=0.0001),
      respectively, in normotensive subjects. In the multivariate analyses, such
      correlations were observed mainly in the normotensive group, whereas there was no
      association among hypertensive subjects regardless of antihypertensive medication
      status. CONCLUSION: baPWV is moderately correlated with the stiffness parameters
      for the proximal AA, mainly in normotensive subjects.

PMID- 23882290
TI  - Anomalous separate origin of left anterior descending coronary artery: presented
      as acute anterior myocardial infarction.
AB  - Coronary artery anomalies are rare presentations in primary percutaneous coronary
      interventions of acute myocardial infarction. Herein, we report the case of a 59
      year-old man with acute anterior myocardial infarction who had anomalous separate
      origin of left anterior descending artery (LAD) and left circumflex artery (LCX)
      from the left coronary aortic sinus. Coronary angiography showed a normal right
      coronary artery and LCX, but no visualization of the LAD. After several
      unsuccessful attempts to cannulate the LAD, we found the LAD ostium located by
      the side of the LCX ostium. There was total occlusion at proxymal LAD. Coronary
      computed tomography angiography demonstrated the precise, separate origin of LAD
      and LCX from the left coronary aortic sinus. 

PMID- 23882289
TI  - Protective effect of survivin in Doxorubicin-induced cell death in h9c2 cardiac
      myocytes.
AB  - BACKGROUND AND OBJECTIVES: Apoptosis has been known to be an important mechanism
      of doxorubicin-induced cardiotoxicity. Survivin, which belongs to the inhibitor
      of apoptosis protein family, is associated with apoptosis and alteration of the
      cardiac myocyte molecular pathways. Therefore, we investigated the anti-apoptotic
      effect and cellular mechanisms of survivin using a protein delivery system in a
      doxorubicin-induced cardiac myocyte injury model. MATERIALS AND METHODS: We
      constructed a recombinant survivin which was fused to the protein transduction
      domain derived from HIV-TAT protein. In cultured H9c2 cardiac myocytes, TAT
      survivin (1 uM) was added for 1 hour prior to doxorubicin (1 uM) treatment for 24
      hours. Cell viability and apoptosis were evaluated by 2-(4,5-dimethyltriazol-2
      yl)-2,5-diphenyl tetrazolium bromide assay, caspase-3 activity, and terminal
      deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay. We measured
      the expression levels of several apoptosis-related signal proteins. RESULTS: The
      survivin level was significantly reduced in a dose dependent manner up to 1 uM of
      doxorubicin in concentration. Purified recombinant TAT-survivin protein was
      efficiently delivered to H9c2 cardiac myocytes, and its transduction showed an
      anti-apoptotic effect, demonstrated by reduced caspase-3 activity and the
      apoptotic index, concomitantly with increased cell viability against doxorubicin
      injury. The phosphorylation of p38 mitogen-activated protein (MAP) kinase and the
      release of Smac from mitochondria were suppressed and the expression levels of
      Bcl-2 and cAMP response element-binding protein (CREB), the transcription factor
      of Bcl-2, were recovered following TAT-survivin transduction, indicating that
      survivin had an anti-apoptotic effect against doxorubicin injury. CONCLUSION: Our
      results suggest that survivin has a potentially cytoprotective effect against
      doxorubicin-induced cardiac myocyte apoptosis through mechanisms that involve a
      decrease in the phosphorylation of p38 MAP kinase, mitochondrial Smac release,
      and increased expression of Bcl-2 and CREB.

PMID- 23882291
TI  - Spontaneous coronary artery dissection and woven coronary artery: three cases and
      a review of the literature.
AB  - Spontaneous coronary artery dissection (SCAD) and woven coronary artery anomaly
      (WCAA) are relatively rare. A few of the previously reported woven coronary
      artery cases have involved in a single coronary artery. We present an unusual
      woven case involving all coronary arteries and two patient with SCAD. We have
      also reviewed the literature related to these disease, as they resemble one
      another. 

PMID- 23882293
TI  - A hybrid procedure for atrial fibrillation using total thoracoscopic ablation and
      post-procedural electrophysiological confirmation of ablation lines.
AB  - Atrial fibrillation (AF) is the most common chronic arrhythmia in the world, and
      it is associated with an increased long-term risk of stroke, heart failure, and
      all-cause mortality. To overcome the limitations of transvenous radiofrequency
      (RF) ablation for AF, total thoracoscopic ablation (TTA) has evolved as a new
      technique. TTA has several advantages over transvenous RF ablation and is known
      to produce better outcomes, especially in patients with persistent AF. Herein, we
      report 2 cases of successful TTA followed by an electrophysiological study
      confirming satisfactory ablation lines; the first such procedure reported in
      Korea. 

PMID- 23882292
TI  - A case of abdominal aortic aneurysm with short angulated proximal neck treated
      with the chimney graft technique.
AB  - Endovascular aneurysm repair (EVAR) using stent grafts has shown to be an
      effective alternative to surgical repair in treating an abdominal aortic aneurysm
      (AAA). EVAR is associated with shorter hospital stays, less blood loss, shorter
      operating times, and lower early morbidity and mortality compared to open
      surgical repair, although EVAR required a higher reintervention rate during a
      longer follow-up period. However, short or severely an angulated infrarenal
      proximal aortic neck is considered unsuitable for EVAR. The chimney graft
      technique is a modified procedure based on the deployment of a covered or bare
      metal stent parallel to the main aortic endograft within the aneurysm, thereby
      creating a conduit that runs outside the aortic main endograft to preserve flow
      to the aortic branches. In this case report, we present a 78-year-old patient
      with an AAA with a short and severely angulated proximal neck who was
      successfully treated by EVAR using the chimney graft technique. 

PMID- 23882294
TI  - An iatrogenically unmasked life threatening disease: brugada syndrome.
AB  - Brugada syndrome is a life threatening disease that is usually overlooked during
      emergency service admissions. It is characterized by typical electrocardiography
      resembling right bundle branch block, static or dynamic ST-segment elevation in
      leads V 1-3. There is familial tendency in some cases. A majority of patients
      have a structurally normal heart and are likely to remain asymptomatic, however
      they may present to emergency departments with syncope and various serious
      arrhythmias. Therefore it is crucially important for emergency medicine
      physicians not to omit this potential diagnosis. Herein we report a case with
      Brugada syndrome which was iatrogenically unmasked after propafenone
      administration for atrial fibrillation. 

PMID- 23882295
TI  - Percutaneous closure of the acquired gerbode shunt using the amplatzer duct
      occluder in a 3-month old patient.
AB  - The Gerbode shunt, known as the left ventricle to the right atrial communication,
      is a rather rare finding, following surgical closure of septal defects. Even
      though the surgical closure is accepted as a treatment of choice, we report a
      successful percutaneous transcatheter closure of the Gerbode shunt in a 3-months
      old baby who weighed 3 kilograms. 

PMID- 23882296
TI  - Left atrial thrombus in a patient with mitral bioprosthetic valve.

PMID- 23882298
TI  - The impact of human immunodeficiency virus infection on cervical preinvasive and
      invasive neoplasia in South Africa.
AB  - OBJECTIVES: Sub-Saharan Africa is at the epicentre of the human immunodeficiency
      virus (HIV) epidemic and has the highest incidence of invasive cervical cancer
      (ICC) in the world. Access to highly active antiretroviral treatment (HAART) in
      South Africa is still limited and provided only to nonpregnant women with a CD4+
      T-cell count <200 MUg/L. We evaluated the relative distribution of cervical
      preinvasive and invasive neoplasia among HIV-infected (treated or not) and
      uninfected women in the Limpopo Province of South Africa. METHODS: We compared
      the consecutive biopsy-diagnosed cervical pathology of 1,023 HIV-infected and
      1,023 uninfected women. We investigated the influence of the CD4+ T-cell count
      and of HAART on the relative distribution of cervical pathology. RESULTS: There
      was a significantly higher proportion of cervical intraepithelial neoplasia
      (CIN)1 (P = 0.012) and 2 (P = 0.01) but a lower proportion of ICC (P = 0.015)
      among HIV-infected women. Patients on HAART had less CIN1 (P = 0.018), 2 (P =
      0.18) and ICC (P = 0.019) that their untreated counterparts. The mean CD4 count
      was similar regardless of cervical lesions and HAART or no treatment. CONCLUSION:
      Our data support the concept that HIV-infected women exhibit a higher rate of
      high-grade preinvasive lesions than uninfected controls. However, they have a
      significantly lower rate of ICC as compared with uninfected counterparts. The
      inclusion of ICC among acquired immune deficiency syndrome-defining illnesses is
      questionable.

PMID- 23882299
TI  - Vertical microbubble column-A photonic lab-on-chip for cultivation and online
      analysis of yeast cell cultures.
AB  - This paper presents a vertically positioned microfluidic system made of
      poly(dimethylsiloxane) (PDMS) and glass, which can be applied as a microbubble
      column (MUBC) for biotechnological screening in suspension. In this MUBC,
      microbubbles are produced in a cultivation chamber through an integrated nozzle
      structure. Thus, homogeneous suspension of biomass is achieved in the cultivation
      chamber without requiring additional mixing elements. Moreover, blockage due to
      produced carbon dioxide by the microorganisms-a problem predominant in common,
      horizontally positioned microbioreactors (MBRs)-is avoided, as the gas bubbles
      are released by buoyancy at the upper part of the microsystem. The patterned PDMS
      layer is based on an optimized two-lithographic process. Since the naturally
      hydrophobic PDMS causes problems for the sufficient production of microbubbles, a
      method based on polyelectrolyte multilayers is applied in order to allow
      continuous hydrophilization of the already bonded PDMS-glass-system. The MUBC
      comprises various microelements, including stabilization of temperature, control
      of continuous bubble formation, and two optical configurations for measurement of
      optical density with two different sensitivities. In addition, the simple and
      robust application and handling of the MUBC is achieved via a custom-made modular
      plug-in adapter. To validate the scalability from laboratory scale to microscale,
      and thus to demonstrate the successful application of the MUBC as a screening
      instrument, a batch cultivation of Saccharomyces cerevisiae is performed in the
      MUBC and compared to shake flask cultivation. Monitoring of the biomass growth in
      the MUBC with the integrated online analytics resulted in a specific growth rate
      of 0.32 h(-1), which is almost identical to the one achieved in the shake flask
      cultivation (0.31 h(-1)). Therefore, the validity of the MUBC as an alternative
      screening tool compared to other conventional laboratory scale systems in
      bioprocess development is proven. In addition, vertically positioned
      microbioreactors show high potential in comparison to conventional screening
      tools, since they allow for high density of integrated online analytics and
      therefore minimize time and cost for screening and guarantee improved control and
      analysis of cultivation parameters. 

PMID- 23882300
TI  - On-chip three-dimensional tumor spheroid formation and pump-less perfusion
      culture using gravity-driven cell aggregation and balanced droplet dispensing.
AB  - This paper presents a spheroid chip in which three-dimensional (3D) tumor
      spheroids are not only formed by gravity-driven cell aggregation but also
      cultured at the perfusion rates controlled by balanced droplet dispensing without
      fluidic pumps. The previous spheroid chips require additional off-chip processes
      of spheroid formation and extraction as well as bulky components of fluidic
      pumps. However, the present spheroid chip, where autonomous medium droplet
      dispensers are integrated on a well array, achieves the on-chip 3D tumor spheroid
      formation and perfusion culture using simple structure without bulky fluidic
      pumps. In the experimental study, we demonstrated that the spheroid chip
      successfully forms 3D tumor spheroids in the wide diameter range of 220 MUm-3.2
      mm (uniformity > 90%) using H358, H23, and A549 non-small cell lung cancer cells.
      At the pump-less perfusion culture (Q = 0.1-0.3 MUl/min) of spheroids, the number
      of H358 cells in the spheroid increased up to 50% from the static culture (Q = 0
      MUl/min) and the viability of the cultured cells also increased about 10%.
      Therefore, we experimentally verified that the perfusion environment created by
      the spheroid chip offers a favourable condition to the spheroids with high
      increase rate and viability. The present chip achieves on-chip 3D tumor spheroid
      formation and pump-less perfusion culture with simple structure, thereby
      exhibiting potential for use in integrated in-vivo-like cell culture systems. 

PMID- 23882301
TI  - The extensor pollicis brevis: a review of its anatomy and variations.
AB  - INTRODUCTION: The standard anatomical description of the extensor pollicis brevis
      tendon provided in textbooks of anatomy is at odds with that of published
      anatomical studies. It is crucial to the hand surgeon that he or she has a clear
      understanding of its anatomy, including its variations. The aim of this study was
      to provide a comprehensive review of the current literature on the anatomy and
      variants of the extensor pollicis brevis. It is hoped that this review will be
      indispensable to the hand surgeon in informing him or her about the anatomy and
      variants encountered when dealing with the extensor pollicis brevis. METHODS:
      Inclusion and exclusion criteria were defined and a literature search was carried
      out on MEDLINE, PubMed, Embase, and Google Scholar from inception to March 2013
      for studies on the topic of extensor pollicis brevis anatomy. The following key
      words were used: "extensor pollicis brevis," "anatomy," "anatomic variations,"
      "cadaveric study," "clinical study," "case report," and "dissection". RESULTS:
      The search retrieved a total of 52 studies following removal of duplicates. Forty
      five studies were excluded following screening of the title and abstract. Three
      studies were excluded as they did not meet the eligibility criteria, leaving 4
      cadaveric studies for inclusion in the review. CONCLUSION: We recommend the use
      of ultrasound scanning to determine anatomy of the extensor pollicis brevis
      before reconstructive procedures involving the extensor pollicis brevis, as well
      as in traumatic injuries to the extensor pollicis brevis. There appears to be
      ethnicity-related variations in the anatomy of the extensor pollicis brevis, and
      further study into these variations may be indicated.

PMID- 23882302
TI  - Linear IgA bullous dermatosis.

PMID- 23882303
TI  - Management of chronic gluteal follicular occlusive disease.

PMID- 23882304
TI  - Syndactyly repair.

PMID- 23882305
TI  - Application of protease technology in dermatology: rationale for incorporation
      into skin care with initial observations on formulations designed for skin
      cleansing, maintenance of hydration, and restoration of the epidermal
      permeability barrier.
AB  - This article reviews background on proteases and their functions, their
      physiological significance in skin, and the potential implications of
      incorporating specific proteases and protease blends into dermatological
      products, including skin care formulations. The history of protease blend
      formulations used in wound model studies and for other disorders is reviewed. In
      vitro data with use of a specific 3-protease blend with evaluation of the impact
      on various skin proteins and peptides is also discussed in this article. 

PMID- 23882306
TI  - A Novel Glycinate-based Body Wash: Clinical Investigation Into Ultra-mildness,
      Effective Conditioning, and Improved Consumer Benefits.
AB  - OBJECTIVE: To assess the properties of a novel body wash containing the mild
      surfactant glycinate. DESIGN: Biochemical and clinical assays. SETTING: Research
      laboratories and clinical sites in the United States and Canada. PARTICIPANTS:
      Women 18 to 65 years of age (cleansing efficacy); male and female subjects 26 to
      63 years of age with mild or moderate dryness and erythema (leg-controlled
      application test); subjects 5 to 65 years of age with mild-to-moderate eczema
      (eczema compatibility); and women 18 to 64 years of age (home use). MEASUREMENTS:
      Assessments across studies included colorimetric dye exclusion to assess skin
      damage potential (corneosurfametry), efficacy of cosmetic product removal from
      skin, change from baseline in visual dryness, change from baseline in Eczema Area
      and Severity Index, and self-perceived eczema attributes and self-reported
      product preference. RESULTS: The glycinate-based cleanser demonstrated mildness
      to skin components when evaluated in a corneosurfametry assay. Short-term use
      under exaggerated wash conditions in subjects with dryness scores <3 and erythema
      scores <2 (both on a 0-6 scale) indicated an initial reduction in visual dryness.
      In subjects with eczema, normal use resulted in significant improvements (p<0.05)
      at Week 4 compared with baseline in skin dryness (change from baseline = -0.73),
      rash (-0.56), itch (-0.927), tightness (-0.585), and all eczema (-0.756). The
      glycinate-based body wash removed 56 percent of a long-lasting cosmetic
      foundation from skin compared with less than 30 percent removed by two
      competitive products tested. The glycinate-based body wash was preferred over a
      competitive mild cleansing product overall. CONCLUSION: The patented glycinate
      containing body wash demonstrated better product mildness and patient-preferred
      attributes and clinical benefits.

PMID- 23882307
TI  - Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.
AB  - Drug rash with eosinophilia and systemic symptoms syndrome is a severe
      idiosyncratic drug reaction with a long latency period. It has been described
      using many terms; however, drug rash with eosinophilia and systemic symptoms
      syndrome appears to be the most appropriate. This syndrome causes a diverse array
      of clinical symptoms, anywhere from 2 to 8 weeks after initiating the offending
      drug. Standardized criteria for the diagnosis have been developed; however, their
      utility remains to be validated. Unfortunately, the management of drug rash with
      eosinophilia and systemic symptoms syndrome is not well supported by strong
      evidence-based data. 

PMID- 23882308
TI  - Penile syringoma: reports and review of patients with syringoma located on the
      penis.
AB  - BACKGROUND: Syringoma of the penis is rare. PURPOSE: This paper describes two men
      with syringoma of the penis and summarizes the clinical features of previously
      reported men with this condition. METHODS: A 25-year-old African man presented
      with a nonpruritic flesh-colored papule on the right side of his proximal dorsal
      penile shaft and a 22-year-old Caucasian man presented with multiple asymptomatic
      flesh-colored papules on his ventral and lateral penis. Neither man had similar
      lesions elsewhere or a family member with this condition. Reports of patients
      with penile syringoma were identified using a medical search engine (PubMed
      Central) and references included in the published papers on this subject.
      RESULTS: Microscopic examination of both men's papules showed syringoma.
      Including these individuals, syringoma exclusively localized to the penis has
      only been reported in 11 men. It usually presents as multiple asymptomatic flesh
      colored papules on the dorsal penile shaft of men less than 30 years of age.
      Epithelial-lined cystic spaces containing homogenous eosinophilic material are
      noted in the fibrotic upper dermis. The papules do not recur following excisional
      biopsy. CONCLUSION: Syringoma exclusively located on the penis is extraordinary
      and has only been reported in 11 men. It presents as a solitary papule or
      multiple asymptomatic papules on the penile shaft. Microscopic examination shows
      epithelial structures and eccrine ducts with comma-like tails resembling tadpoles
      in the fibrotic upper dermis; amorphous pink secretion is often present in the
      epithelial-lined spaces. Excision of the penile papules not only provides the
      diagnosis, but also successfully removes the individual lesion without
      recurrence.

PMID- 23882309
TI  - Neonate with annular plaques of the scalp.

PMID- 23882310
TI  - Extended-release Formulation of Minocycline in the Treatment of Moderate-to
      severe Acne Vulgaris in Patients Over the Age of 12 Years.
AB  - Oral antibiotics continue to play an important role in the treatment of moderate
      to-severe acne. Minocycline is widely used in moderate-to-severe acne.
      Minocycline has anti-inflammatory properties, activity against Propionibacterium
      acnes and lipophilicity. An extended-release formulation of minocycline has been
      introduced. Extended-release minocycline is not bioequivalent to nonmodified
      release minocycline products and exhibits dose-proportional pharmacokinetics.
      Food or dairy products did not influence absorption. Efficacy is not dose
      dependent, while the incidence of acute vestibular adverse events increases with
      dose suggesting an optimal dose of 1mg/kg. In two Phase 3 clinical trials, mean
      percent improvement in inflammatory lesions after 12 weeks of treatment with
      extended-release minocycline was 43.1 and 45.8 percent compared to 31.7 and 30.8
      percent with placebo (P=0.001 and P<0.001, respectively) while the incidence of
      acute vestibular adverse events was comparable to placebo. 

PMID- 23882311
TI  - Use of intralesional cryosurgery as an innovative therapy for keloid scars and a
      review of current treatments.
AB  - Keloids are benign growths characterized by excessive collagen formation. The
      treatment of keloid scars remains a challenging clinical dilemma for both
      patients and providers. Intralesional cryosurgery has emerged as a safe and
      effective new treatment by destroying the hypertrophic scar tissue with minimal
      damage to the skin surface. 

PMID- 23882312
TI  - Causes and recommendations for unanticipated ink retention following tattoo
      removal treatment.
AB  - While placement of ink into the skin is a long-standing tradition, patients are
      now seeking tattoo removal on a more frequent basis. Once considered acceptable
      removal options, tattoo ink removal via physical destruction included
      dermabrasion, chemical destruction, salabrasion, thermal destruction, and
      cryotherapy. Now these options are used extremely infrequently. These modalities
      provided unpredictable results and often required prolonged healing times and
      left patients with skin discoloration, pain, scarring, and ink retention. Even
      the widely adopted use of lasers, now considered the gold standard method, offers
      some level of unpredictability surrounding the natural progression of ink
      resolution. Multiple factors need to be taken into consideration when
      successfully removing tattoo pigment including the modalities used, number and
      frequency of treatments, proper device technique, and physiological barriers to
      tattoo removal. This paper serves to elucidate the common causes of ink retention
      following tattoo removal treatment with recommendations on how best to address
      this relatively common occurrence. 

PMID- 23882313
TI  - Linear Lumbar Localized Lysis of Elastic Fibers: A Distinctive Clinical
      Presentation of Mid-dermal Elastolysis.
AB  - BACKGROUND: The absence or loss of elastic fibers in the skin is referred to as
      dermal elastolysis. PURPOSE: This paper describes a woman with a distinctive
      clinical presentation of mid-dermal elastolysis characterized morphologically by
      multiple horizontal raised bands on the lower back. METHODS: A 20-year-old
      Filipino woman presented with multiple asymptomatic, flesh-colored, raised, firm,
      linear, cord-like bands on the lumbar area of her back. There were neither
      similar lesions elsewhere nor a family member with this condition. RESULTS:
      Microscopic examination of the raised band showed nearly complete absence of
      elastic fibers in the mid dermis. In contrast, a biopsy of symmetrically located
      normal-appearing skin showed a uniform distribution of elastic fibers throughout
      the dermis. Linear lumbar localized elastolysis is a descriptive designation that
      accurately reflects a correlation of the clinical and pathological changes of
      this condition. CONCLUSION: The clinical differential of raised horizontal cord
      like bands on the lower back (without a family history of an inherited elastic
      fiber disorder, a prior history of trauma, or a significant change in weight or
      exercise habit) includes linear focal elastosis and linear lumbar localized
      elastolysis. Microscopic evaluation of a Verhoeff-van Gieson stained lesion
      specimen (which may be accompanied by a biopsy of normal-appearing skin for
      comparison) will readily differentiate these conditions. The former is usually
      characterized by increased elastic fibers, whereas the latter, as in this
      patient, shows a paucity or absence of elastic fibers in the mid dermis.

PMID- 23882314
TI  - Introduction of the Microdroplet Technique with Incobotulinumtoxin A for the
      Treatment of Crow's Feet.
AB  - To investigate the efficacy and safety of the addition of the microdroplet
      technique to conventional injections for the treatment of crow's feet with
      incobotulinumtoxin A, four women with moderate-to-severe crow's feet at maximum
      expression received three standard intradermal injections of incobotulinumtoxin A
      on both sides of the face (4U [0.1mL] at each injection point) plus six
      microdroplet injections of incobotulinumtoxin A (0.5U [0.025mL] per point) into
      the lateral canthal area on the left side of the face and an equal quantity of
      saline at the same injection points on the right side of the face. Investigators
      and subjects independently evaluated the degree of rhytide improvement both at
      rest and maximum expression after 28 and 84 days. Investigator and subject
      ratings for wrinkle severity at maximum expression were improved to a greater
      degree on the side of the face treated with additional microdroplet
      incobotulinumtoxin A in all subjects, except one who was over 65 years old. All
      women preferred the results on the left side of their face. Treatment was well
      tolerated. The addition of the microdroplet technique to standard practice for
      injecting incobotulinumtoxin A is a promising procedure for the treatment of
      crow's feet in women with moderate-to-severe wrinkles. 

PMID- 23882315
TI  - A patch of hair loss on the scalp.

PMID- 23882316
TI  - Retraction note.

PMID- 23882317
TI  - The utility of the initial electrocardiogram in predicting acute coronary events
      in current cocaine users with chest pain in the emergency department.
AB  - INTRODUCTION: Chest pain suggestive of myocardial ischemia or infarction is a
      common emergency department complaint and a subset of these is associated with
      cocaine use. It can be difficult to triage patients with chest pain while using
      cocaine. OBJECTIVE: To assess the reliability of the initial electrocardiogram
      (ECG) done in the emergency department in current cocaine users suspected of
      acute coronary syndrome (ACS) in predicting a true event. METHODS: A total of 218
      charts of current cocaine users who presented with chest pain judged as possibly
      cardiac in nature with an initial ECG from September 2003 to August 2007 were
      reviewed. Initial ECG was classified into: (1) Category A (inverted T waves in
      two or more contiguous leads and/or characteristic ST segment elevation or
      depression indicative of an ischemic event possibly acute); (2) Category B (other
      ischemic changes but without any ST or T abnormalities such as Q wave, or bundle
      branch block); or (3) Category C (normal tracing, non-specific ST segment or T
      wave alterations). RESULTS: Eighteen of 218 (8.3%) were confirmed to have ACS.
      Ten of 18 confirmed ACS patients were among the 70 cases with ECG classified as
      Category A. One hundred and one of 218 were Category C ECGs: five of these had
      ACS (three of the five had significant cardiac history) and 96 did not,
      consistent with 95% negative predictive value. Patients with Category A ECG
      characteristics were three times at risk to have ACS compared with a Category C
      ECG. CONCLUSION: The initial ECG with a good clinical history can be used
      effectively to triage patients presenting with chest pain and current use of
      cocaine in the emergency department.

PMID- 23882318
TI  - Acute coronary syndrome in a patient with coexistent conduction abnormality.

PMID- 23882319
TI  - Open access, a revolution in scholarly publishing.

PMID- 23882320
TI  - Design and implementation of a longitudinal ambulatory clerkship in the first
      year curriculum at the Johns Hopkins School of Medicine.
AB  - In response to calls for medical education reform we designed and implemented a
      new Longitudinal Ambulatory Clerkship (LAC) at the Johns Hopkins University
      School of Medicine. The LAC provides first-year medical students with their
      initial exposure to clinical medicine during a 12-month experience consisting of
      weekly clinic sessions with a practicing physician-mentor (preceptor) and
      longitudinal experience with a population of patients. The LAC allows students to
      experience firsthand many of the personal, professional, and organizational
      issues that impact the practice of medicine. This paper reviews the rationale,
      development, and challenges during implementation of this clerkship. 

PMID- 23882321
TI  - Sporadic urban leptospirosis.
AB  - Severe leptospirosis (Weil Syndrome) was diagnosed in an otherwise healthy
      environmental worker in Baltimore alleys in late November 2010. He developed
      multiple organ failure but responded to antibiotic therapy and experienced a full
      recovery within 4 weeks. His diagnosis was confirmed by a rise in indirect
      hemagglutinin titer (acute 0, convalescent 400). The subject had close contact
      with Baltimore alley rats; a similar epidemiologic exposure and location reported
      in an outbreak 15 years ago. 

PMID- 23882322
TI  - Origins of JCHIMP.

PMID- 23882323
TI  - Is it really sinus tachycardia?

PMID- 23882325
TI  - Patient safety in community-based teaching hospitals.

PMID- 23882324
TI  - Antimicrobial stewardship: attempting to preserve a strategic resource.
AB  - Antimicrobials hold a unique place in our drug armamentarium. Unfortunately the
      increase in resistance among both gram-positive and gram-negative pathogens
      coupled with a lack of new antimicrobial agents is threatening our ability to
      treat infections. Antimicrobial use is the driving force behind this rise in
      resistance and much of this use is suboptimal. Antimicrobial stewardship programs
      (ASP) have been advocated as a strategy to improve antimicrobial use. The goals
      of ASP are to improve patient outcomes while minimizing toxicity and selection
      for resistant strains by assisting in the selection of the correct agent, right
      dose, and best duration. Two major strategies for ASP exist: restriction/pre
      authorization that controls use at the time of ordering and audit and feedback
      that reviews ordered antimicrobials and makes suggestions for improvement. Both
      strategies have some limitations, but have been effective at achieving
      stewardship goals. Other supplemental strategies such as education, clinical
      prediction rules, biomarkers, clinical decision support software, and
      institutional guidelines have been effective at improving antimicrobial use. The
      most effective antimicrobial stewardship programs have employed multiple
      strategies to impact antimicrobial use. Using these strategies stewardship
      programs have been able to decrease antimicrobial use, the spread of resistant
      pathogens, the incidence of C. difficile infection, pharmacy costs, and improved
      patient outcomes. 

PMID- 23882326
TI  - The Evolution of JCHIMP.

PMID- 23882327
TI  - Hand hygiene strategies.
AB  - Hand hygiene is one of the major players in preventing healthcare associated
      infections. However, healthcare workers compliance with hand hygiene continues to
      be a challenge. This article will address strategies to help improving hand
      hygiene compliance. 

PMID- 23882328
TI  - Hypoglycemia in the hospital.
AB  - Hypoglycemia is a common adverse event affecting hospitalized patients with
      diabetes. This paper reviews the data regarding optimization of glucose in
      hospitalized patients, discusses the scope and significance of hypoglycemia in
      the hospital, and makes recommendations on how to reduce the risk of this serious
      adverse event. 

PMID- 23882330
TI  - Hyperkalemia and severe rhabdomyolysis.

PMID- 23882329
TI  - Valsalva maneuver: shortest optimal expiratory strain duration.
AB  - PURPOSE: To quantitate the level of difficulty and determine consistency of
      hemodynamic responses with various expiratory strain (ES) durations. METHODS:
      Thirty-four healthy subjects performed the Valsalva maneuver (VM) with an ES
      duration of 10, 12, and 15 seconds in random order. Level of difficulty after
      each trial was rated 1 to 10, with 10 being the most difficult. Blood pressure
      and heart rate (HR) were recorded continuously and non-invasively. Parameters
      studied were Valsalva ratio (VR), early phase II (IIE), late phase II (IIL),
      tachycardia latency (TL), bradycardia latency (BL), and overshoot latency (OV-L).
      Consistency of responses was calculated. RESULTS: DIFFICULTY INCREASED
      SIGNIFICANTLY WITH INCREASED ES DURATION: 5.1+/-0.1 (mean+/-SEM) at 10 seconds,
      5.9+/-0.1 at 12 seconds, and 6.8+/-0.1 at 15 seconds (p<0.001). Phase IIE, TL,
      BL, OV-L, and VR response did not differ statistically with increasing ES
      durations, and there were no differences in variability. Phase IIL response
      increased significantly with increasing ES duration. Phase IIL was poorly
      delineated in 14 of 102 trials with 10 seconds ES duration. CONCLUSIONS: ES
      duration of 10 seconds created a low level of difficulty in healthy individuals.
      This strain duration produced consistent hemodynamic response for all parameters
      tested except IIL phase. The absence of IIL phase with 10 seconds ES should not
      be interpreted as an indicator of sympathetic vasoconstrictor failure.

PMID- 23882331
TI  - Applying for a sub-specialty fellowship: some tips and advice from a former
      program director.
AB  - Successfully completing an internal medicine residency is a great accomplishment.
      With the great need for primary care physicians, many residents are considering
      entering the field of general medicine where one can care for the whole patient.
      However, for those who have a drive to become an expert in one particular organ
      system, the path to the completion of training is only half over. Though you may
      think you have figured out the 'application process' after successfully gaining
      admission to college, medical school, and residency, there is one more hurdle
      that stands between you and your ultimate goal of sub-specialization - the
      fellowship application process. Unfortunately, this last application may be the
      most difficult of all. As a former cardiology program director, I have trained
      over 100 fellows and reviewed over 3,000 applications. Here is some practical
      advice from the 'inside' on how to be successful at this process. 

PMID- 23882332
TI  - Current coronary intervention controversy: who's to judge?

PMID- 23882333
TI  - Communication Tools for the Modern Doctor Bag. Physician Patient Communication
      Part 1: Beginning of a medical interview.
AB  - Effective physician patient communication is essential to best practice in
      medicine. Good communication with patients is critical in making the right
      diagnosis, improving compliance and overall outcomes for our patients (as well as
      improving physician satisfaction.) Communication skills can be learned and need
      to be taught, practiced and given the same emphasis as other core competencies in
      medicine. The focus of this article is on the Calgary-Cambridge Model for
      physician patient communication in the context of a medical interview. The
      beginning of a patient encounter is discussed, with emphasis on appropriate
      introductions and attentive active listening. 

PMID- 23882334
TI  - Resident scholary work in the community hospital setting.

PMID- 23882335
TI  - Lung cancer in the very elderly: incidence, presentation, and diagnostic decision
      making. A retrospective analysis at a teaching community hospital.
AB  - BACKGROUND AND OBJECTIVES: Lung cancer presentation and decision-making in the
      very elderly patient population, 80 years of age and older, was studied given the
      projected increase in cancer incidence in the very elderly and yet only limited
      management guidelines. DESIGN AND SETTING: A 10-year experience at the Unity
      Health System of Rochester, NY, was reviewed using tumor registry data for the
      entire lung cancer population plus focused medical record review of very elderly
      patients. A questionnaire survey on the clinical approach to lung cancer in the
      elderly was distributed to medical staff involved in their care. PARTICIPANTS
      MEASUREMENTS AND RESULTS: Of 997 patients, approximately 100 cases each year, the
      very elderly comprised 18% of patients from year 1998 through 2002, and 23% from
      year 2003 through 2007. One-third of the very elderly were diagnosed with lung
      cancer on clinical grounds without tissue confirmation. The majority of this
      group had cardio-pulmonary symptoms and an advanced clinical stage. The very
      elderly had no tissue sampling as per their own decision in 12 of 44 of cases,
      per family decision in 28 of 44, and per physician and other input in 4 of 44.
      Physicians stated that patient wishes and health-related factors, more so than
      socio-economic factors, were primary concerns for management decision-making.
      CONCLUSIONS: The number of very elderly lung cancer patients in this community
      setting has been significant and appears to be increasing. These patients were
      more likely to have an incomplete diagnostic work-up, with patient and family
      wishes being the major factor in medical decision-making. The physician approach
      to these patients emphasized patient autonomy and medical factors.

PMID- 23882336
TI  - Correlation of admitted nursing home residents' hospital length of stay and
      vitamin D levels.
AB  - OBJECTIVE: To determine the relationship between low vitamin D levels and
      hospital length of stay in nursing home residents who were admitted to acute
      medical floors in an urban community teaching hospital. METHODS: This prospective
      cohort study used multiple regression analysis for patients transferred from
      nursing homes to the hospital. On admission, patients' serum 25(OH)D levels were
      obtained by blood draw using partially purified lipid extracts via a competitive
      protein binding assay. We defined low levels of serum 25(OH)D as <30 ng/ml.
      Patient medical histories were compiled by retrospective chart review and/or
      patient interview. Medical histories were analyzed with special emphasis on
      history of falls, osteoporosis, comorbidities, medication profile, and hospital
      length of stay. RESULTS: The mean serum 25(OH)D level for 71 patients (N = 71)
      was 22.69 ng/ml (+/-SD 10.967); the median, 23 ng/ml. Low serum concentrations of
      25(OH)D were recorded in 51 patients (72%) all of whom had a longer mean hospital
      length of stay (13.72 days +/- SD 10.778) than the 20 patients with higher
      vitamin D levels (7.72 days +/- SD 4.070). CONCLUSION: Low vitamin D levels in
      nursing home residents admitted to a community hospital were directly associated
      with increased hospital length of stay.

PMID- 23882337
TI  - Moxifloxacin-warfarin interaction.
AB  - Two case reports presented here show elevated prothrombin time/international
      normalized ratios (PT/INR) following coadministration of warfarin and
      moxifloxacin. Although the underlying mechanism of this interaction still remains
      unclear, health care providers should be careful when prescribing moxifloxacin to
      patients on warfarin therapy, especially to patients with low albumin levels.
      More frequent monitoring of INR in these patients may be warranted. 

PMID- 23882338
TI  - Atrial flutter with aberrant conduction in a patient taking amphetamine salts and
      caffeine.
AB  - A case is presented of a man with a life-threatening tachyarrhythmia precipitated
      by ingested substances. 

PMID- 23882339
TI  - My appendectomy.
AB  - A personal experience of a medical resident with appendicitis. 

PMID- 23882340
TI  - Osborn waves in a hypothermic patient.

PMID- 23882341
TI  - Treatment and pathogenesis of acute hyperkalemia.
AB  - This article focuses on the pathogenesis, clinical manifestations, and various
      treatment modalities for acute hyperkalemia and presents a systematic approach to
      selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused
      by extracellular potassium shift or decreased renal potassium excretion, usually
      presents with non-specific symptoms. Early recognition of moderate to severe
      hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle
      paralysis. Management of hyperkalemia includes the elimination of reversible
      causes (diet, medications), rapidly acting therapies that shift potassium into
      cells and block the cardiac membrane effects of hyperkalemia, and measures to
      facilitate removal of potassium from the body (saline diuresis, oral binding
      resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L
      or EKG changes is a medical emergency and should be treated accordingly.
      Treatment should be started with calcium gluconate to stabilize cardiomyocyte
      membranes, followed by insulin injection, and b-agonists administration.
      Hemodialysis remains the most reliable method to remove potassium from the body
      and should be used in cases refractory to medical treatment. Prompt detection and
      proper treatment are crucial in preventing lethal outcomes. 

PMID- 23882342
TI  - Fatal meningococcemia.
AB  - Within the past six years, a case of bothWaterhouse-Freidrichsen Syndrome and
      fulminant meningococcemia have presented to Union Memorial Hospital. Both cases
      presented in markedly different fashions, differed in microbiologic serogrouping,
      showed minimal histopathologic similarities; however achieved ultimately the same
      outcome through two different pathological pathways. The following case reports
      illustrate two mechanisms through which N. Meningitis may pathogenize a host,
      both leading to complete cardiovascular collapse in less than 12 hours. 

PMID- 23882343
TI  - Anniversary issue of JCHIMP.

PMID- 23882344
TI  - Case of hereditary papillary renal cell carcinoma.
AB  - Renal cell carcinoma is the most common type of renal malignancy and it
      originates from the renal tubular epithelium. Due to the diversity in the
      histopathological and molecular characteristics, it is typically subclassified
      into five different categories. Papillary renal cell carcinoma is one
      subclassification and it includes two variants: sporadic and hereditary. Although
      the hereditary form comprises a smaller number of cases of papillary renal cell
      carcinoma, an understanding of the molecular pathways and genetic changes
      continues to play a significant role in the development of new targeted
      therapies. Along with recommending appropriate lifestyle modification, further
      investigation into the molecular pathogenesis of hereditary papillary renal cell
      carcinoma will continue to be invaluable for the clinical management of renal
      cell carcinoma. In this article, we discuss a case of the hereditary papillary
      renal cell carcinoma along with an overview of the disease. 

PMID- 23882345
TI  - CT scan for suspected acute appendicitis.

PMID- 23882346
TI  - The value of reporting cases.

PMID- 23882347
TI  - Personal health care of internal medicine residents.
AB  - INTRODUCTION: Medical residents, as part of their job to balance the demands of
      their work with caring for themselves so as to be mentally, emotionally, and
      physically sound to stay clinically competent. While regulatory and legislative
      attempts at limiting medical resident work hours have materialized but have yet
      to attain passage, there are fairly little data looking into how residents cope
      up with their demands and yet attend to their own personal health. DESIGN:
      Anonymous mailed survey. SUBJECTS: Three hundred and thirty-seven residents from
      all internal medicine residency programs within United States. METHODS: We
      conducted a survey in the form of a questionnaire that was sent by e-mail to the
      program directors of various internal medicine residency programs within the
      United States, and responses were collected between May 19 and June 21, 2009.
      Response was well appreciated with total number of participants of 337 with even
      demographical distribution in gender, residency year, AMG/IMG, age group. Seventy
      one percent of the residents felt that they would prefer getting admitted to
      their own hospital for any acute medical or surgical condition. Of the 216
      residents who have had received health care in the past, almost half of them
      chose their own hospital because of the proximity, while 45% did not choose their
      own hospital despite proximity. Two out of three residents missed their doctors
      appointments or cancelled them due to demands of medical training. Only half of
      the residents have a primary care physician and almost 80% of them did not have
      their yearly health checkup. Close to 30% held back information regarding their
      social and sexual history from their provider because of privacy and
      confidentiality concerns. Eighty percent of residents never received information
      about barriers that physicians may face in obtaining care for their socially
      embarrassing conditions. Seventy percent felt that their performance then was
      suboptimal because of that health condition and also felt sick but did not drop
      the call. Half of the residents had concerns that they might be having a
      psychiatric illness, but only 5% of them received a formal evaluation at their
      own hospital and 23 (12.4%) at an outside hospital. CONCLUSIONS: It is very
      important to have more studies to emphasize on resident's physical and mental
      health and encourage them to have a primary care physician. There are several
      reasons preventing residents from getting a formal evaluation, confidentiality
      reasons, lack of time - schedule constraints, fear of being labeled, and social
      repercussions are few of them. Program directors should encourage the residents
      to not only care of the health of their patients but also be enthusiastic about
      their personal health issues for upgraded, revised patient care, and ultimately
      for their overall well-being.

PMID- 23882348
TI  - Lack of efficacy of ergocalciferol repletion.
AB  - INTRODUCTION: Vitamin D has become an area of intensive scrutiny, both in medical
      and lay literature. However, there are limited data to suggest proper repletion
      regimens for those patients who have hypovitaminosis D. Consequently, various
      methods are used in clinical practice. The aim of this study was to assess the
      efficacy of various treatment strategies for hypovitaminosis D in an ambulatory
      internal medicine practice. METHODS: A retrospective chart review between October
      2005 and June 2010 of a suburban internal medicine practice was performed via
      query of the electronic medical record (Centricity, General Electric Healthcare,
      UK). Patients with a 25-hydroxyvitamin D concentration less than 32 mg/dl were
      identified and treated. Treatment success was defined as 25-hydroxyvitamin D
      concentrations greater than 32 mg/dl. Statistical analysis to assess changes in
      vitamin D level controlling for season, comorbidities, and demographics were
      used. RESULTS: A total of 607 treatment episodes were identified, with 395
      excluded due to lack of follow-up vitamin D level within 16 weeks, no treatment
      documented, topical treatment, doxercalciferol treatment, or non-compliance. Of
      the remaining patients, there were 212 treatment instances on 178 patients.
      Ergocalciferol 50,000 international units (IU) was used most frequently (71.4% of
      the time.). A higher initial vitamin D level was positively associated with
      treatment success (adjusted odds ratio = 1.11, p=0.002). Increased doses of
      ergocalciferol increased the likelihood of treatment success (p=0.0011). Seasonal
      variation was related to posttreatment 25-hydroxyvitamin D concentration as was
      body mass index (BMI) (p=0.003 and p=0.044). CONCLUSION: Pretreatment levels of
      25-hydroxyvitamin D, BMI, season, and vitamin D dose are predictors of successful
      hypovitaminosis D treatment. Our data suggest that patients with initial 25
      hydroxyvitamin D concentrations of <20 should be treated with a higher total dose
      of ergocalciferol than 50,000 IU for 8 weeks. Further studies, including
      prospective, randomized trials, are needed to determine an optimal treatment
      protocol to account for the numerous variables.

PMID- 23882349
TI  - Perspective on plagiarism.

PMID- 23882350
TI  - Academic workforce trends in community hospitals.
AB  - INTRODUCTION: Obstetrician-gynecologist faculty workforce studies have been
      limited to faculty at university training programs. Not much is known about the
      obstetrician-gynecologist faculty workforce at community programs. METHOD: This
      study assessed the obstetrician-gynecologist faculty workforce in community
      training programs via administering surveys to the department chairs. The
      questionnaire assessed number of current faculty by degree, work status (part
      time/full-time), rank, and sub-specialty. Out of 125 programs, 65 responded (52%
      response rate). RESULTS: The mean number of full-time faculty per department in
      community hospitals was 17 faculty. Two-thirds of community department chairs
      anticipated an increase in full-time faculty and 43% anticipated an increase in
      part-time faculty. Like university programs, sub-specialists and Professors
      (compared to generalists and assistant professors) were more likely to be male.
      CONCLUSION: There are similarities between the community and university faculty
      workforce, many of the community program faculty are involved in research. Given
      the evolving clinical, educational, and research demands on community faculty, it
      is important to continue to monitor and study community program faculty.

PMID- 23882352
TI  - Meningitis retention syndrome.
AB  - A 50-year-old Caucasian woman presented with signs and symptoms of meningitis
      preceded by a 3 day history of flu-like symptoms and progressive difficulty with
      urination. Cerebrospinal Fluid (CSF) analysis was consistent with aseptic
      meningitis. She was found to have a significant urinary retention secondary to
      atonic bladder. MRI of the brain and spine were normal and CSF-PCR (polymerase
      chain reaction) was positive for HSV-2. Urinary retention in the context of
      meningitis and CSF pleocytosis is known as Meningitis Retention Syndrome (MRS).
      MRS is a rare but important complication of meningitis most commonly associated
      with HSV-2. Involvement of central pathways may have a role in the pathogenesis
      of MRS but this is poorly documented. MRS is different from Elsberg syndrome
      wherein patients display features of lumbosacral polyradiculitis or
      radiculomyelitis. Early treatment with antiviral therapy was associated with a
      favorable outcome in our patient. 

PMID- 23882353
TI  - Campylobacteremia in stage IV gliosarcoma with bevacizumab treatment.
AB  - Primary campylobacter enteritis with secondary bacteremia was diagnosed in an
      immunocompromised patient with stage IV gliosarcoma. She developed mild diarrhea
      followed by systemic symptoms with transient generalized weakness and fever. She
      was treated with azithromycin and had a full recovery and without relapse through
      2 months of follow-up. Her diagnosis was confirmed by a positive stool culture
      for Campylobacter sp. and blood culture for Campylobacter jejuni/coli. 

PMID- 23882351
TI  - Acute endocarditis in intravenous drug users: a case report and literature
      review.
AB  - Infective endocarditis (IE) is a notorious complication of intravenous drug use
      (IDU). It typically affects the cardiac valves. Among these, the tricuspid is the
      most common affected valve, although the mitral and/or aortic valves can also be
      involved. Methicillin sensitive staphylococcus aureus (MSSA) is the most common
      etiological microbial agent of IE in IDU. Once IE is diagnosed, antibiotic
      treatment should start immediately after blood cultures have been obtained.
      However, IE in this particular patient population is more difficult to treat, and
      has a high recurrence rate compared to other patient populations, because of
      continuing IDU and medical non-compliance. Here, we present an interesting case
      of IE in a relatively young IDU patient with severe MSSA positive sepsis. The
      updated diagnostic and treatment strategies, as well as the ethical issues
      involved in the management of IE patients in the setting of current active IDU
      will also be discussed. 

PMID- 23882354
TI  - A prediction model for COPD readmissions: catching up, catching our breath, and
      improving a national problem.
AB  - Frequent COPD exacerbations have a large impact on morbidity, mortality and
      health-care expenditures. By 2020, the World Health Organization expects COPD and
      COPD exacerbations to be the third leading cause of death world-wide.
      Furthermore, In 2005 it was estimated that COPD exacerbations cost the U.S.
      health-care system 38 billion dollars. Studies attempting to determine factors
      related to COPD readmissions are still very limited. Moreover, few have used a
      organized machine-learning, sensitivity analysis approach, such as a Random
      Forest (RF) statistical model, to analyze this problem. This study utilized the
      RF machine learning algorithm to determine factors that predict risk for multiple
      COPD exacerbations in a single year. This was a retrospective study with a data
      set of 106 patients. These patients were divided randomly into training (80%) and
      validating (20%) data-sets, 100 times, using approximately sixty variables
      intially, which in prior studies had been found to be associated with patient
      readmission for COPD exacerbation. In an interactive manner, an RF model was
      created using the training set and validated on the testing dataset. Mean area
      under-curve (AUC) statistics, sensitivity, specificity, and negative/positive
      predictive values (NPV, PPV) were calculated for the 100 runs. THE FOLLOWING
      VARIABLES WERE FOUND TO BE IMPORTANT PREDICTORS OF PATIENTS HAVING AT LEAST TWO
      COPD EXACERBATIONS WITHIN ONE YEAR: employment, body mass index, number of
      previous surgeries, administration of azithromycin/ceftriaxone/moxifloxacin, and
      admission albumin level. The mean AUC was 0.72, sensitivity of 0.75, specificity
      of 0.56, PPV of 0.7 and NPV of 0.63. Histograms were used to confirm consistent
      accuracy. The RF design has consistently demonstrated encouraging results. We
      expect to validate our results on new patient groups and improve accuracy by
      increasing our training dataset. We hope that identifying patients at risk for
      frequent readmissions will improve patient outcome and save valuable hospital
      resources. 

PMID- 23882355
TI  - Implementation of a heart failure readmission reduction program: a role for
      medical residents.
AB  - BACKGROUND: Congestive heart failure (CHF) is one of the leading causes of
      hospital readmissions within 30 days of discharge. Due to the substantial costs
      associated with these readmissions, several interventions to reduce CHF
      readmissions have been developed and implemented. METHODS: To reduce CHF
      readmissions at our community teaching hospital, the Smooth Transitions Equal
      Less Readmission (STELR) program was developed. Utilizing the Plan-Do-Check-Act
      cycle for quality improvement, resident physicians tracked patients enrolled in
      the STELR program. The resident contribution to the program was substantial in
      that they were able to quantify the improvement in both physician practices and
      patient readmissions. This provided insight into program areas requiring further
      modification, which the hospital would not have obtained without resident
      participation. RESULTS: The readmission rate for patients diagnosed with heart
      failure decreased from 32% prior to program implementation, to 24% hospital wide
      (including patients who were not tracked in the STELR program), and 21% among
      patients tracked by the residents. CONCLUSION: This effective CHF readmission
      reduction program requires less financial resources compared to government funded
      programs. The resident involvement in the STELR program helped to assess and
      improve the program and also allowed the residents to gain an awareness of the
      resources available to their patients to facilitate their transition home. The
      program exposed the residents to systems-based practice, a fundamental element of
      their residency training and, more generally, community care.

PMID- 23882356
TI  - Novel approaches to the patient with massive hemoptysis.
AB  - Massive hemoptysis is a life-threatening condition with a high mortality when
      treated conservatively. Several modalities have been described in the treatment
      of hemoptysis with varying results. Endobronchial therapy has traditionally been
      performed with rigid bronchoscopy. This requires both specialized training and
      equipment that is not readily available in many centers. The role of fiberoptic
      bronchoscopy (FOB) is unclear in these situations but is more widely accessible.
      We describe three cases of the successful treatment of hemoptysis with FOB. These
      patients were treated with a combination of techniques described previously in
      the literature; however, these methods failed to result in cessation of the
      bleeding. Therefore, we employed alternative strategies not described in the
      literature, using oxidized regenerated cellulose with FOB alone as well as in
      conjunction with endobronchial placement of vascular embolization coils. These
      additional techniques may offer other options when rigid bronchoscopy or other
      modalities are not readily available. 

PMID- 23882357
TI  - Imaging diagnosis of aspergilloma.

PMID- 23882358
TI  - Absolute lymphocyte count as a predictor of Pneumocystis pneumonia in patients
      previously unknown to have HIV.
AB  - This is a retrospective review of patients admitted to an inner city community
      hospital with community-acquired pneumonia who were ultimately diagnosed with
      AIDS and Pneumocystis. Absolute lymphocyte count in our hospital is available
      immediately. In contrast, it can take 48 hours or longer to obtain more specific
      CD-4 counts and AIDS enzyme-linked immunosorbent assay (ELISA) serology. The
      association of lymphopenia with ultimate diagnosis of AIDS and Pneumocystis
      supports immediate empiric treatment for pneumocystis carinii pneumonia (PCP) in
      our highly HIV prevalent hospital. 

PMID- 23882359
TI  - Autoimmune encephalopathy associated with thyroid autoantibodies as the cause of
      reversible cognitive impairment.
AB  - We herewith describe a patient with acute confusion, expressive aphasia and
      generalized seizures. A through workup excluded most causes of encephalopathy. He
      was, however, found to have TSH=18.6 MIU/ml, T3reverse=0.44nmol/L, T4=0.8ng/dl
      and Anti-Thyroid-Peroxidase AB titer >1000 IU/ml. Based on the above findings the
      patient was diagnosed with Hashimoto's encephalopathy and his mental status
      showed dramatic improvement (MMS 30/30) with high dose prednisone. Hashimoto's
      encephalopathy is rare disorder of presumed autoimmune origin characterized by
      cognitive decline, seizures, neuro-psychiatric symptoms, high titers of Anti
      Thyroid-Peroxidase AB, and a positive response to steroids. 

PMID- 23882360
TI  - A brief review: history to understand fundamentals of electrocardiography.
AB  - The last decade of the 19th century witnessed the rise of a new era in which
      physicians used technology along with classical history taking and physical
      examination for the diagnosis of heart disease. The introduction of chest x-rays
      and the electrocardiograph (electrocardiogram) provided objective information
      about the structure and function of the heart. In the first half of the 20th
      century, a number of innovative individuals set in motion a fascinating sequence
      of discoveries and inventions that led to the 12-lead electrocardiogram, as we
      know it now. Electrocardiography, nowadays, is an essential part of the initial
      evaluation for patients presenting with cardiac complaints. As a first line
      diagnostic tool, health care providers at different levels of training and
      expertise frequently find it imperative to interpret electrocardiograms. It is
      likely that an understanding of the electrical basis of electrocardiograms would
      reduce the likelihood of error. An understanding of the disorders behind
      electrocardiographic phenomena could reduce the need for memorizing what may seem
      to be an endless list of patterns. In this article, we will review the important
      steps in the evolution of electrocardiogram. As is the case in most human
      endeavors, an understanding of history enables one to deal effectively with the
      present. 

PMID- 23882361
TI  - Electrical alternans vs. pseudoelectrical alternans.
AB  - Beat-to-beat variations in QRS amplitude or axis may be caused by several
      conditions. 

PMID- 23882362
TI  - Diagnostic yield and renal complications after computed tomography pulmonary
      angiograms performed in a community-based academic hospital.
AB  - BACKGROUND: Venous thromboembolism and pulmonary embolism (VTE/PE) remain a
      diagnostic challenge. The computed tomography pulmonary angiogram (CTPA) has
      emerged as a popular diagnostic test for PE. However, there is limited data on
      diagnostic yield and complications in actual clinical settings. Our goal was to
      determine the diagnostic yield for PE and rate of renal complications following
      CTPA in a large community hospital setting. METHODS: A retrospective chart review
      of 1,514 patients who underwent CTPA in the emergency department or during the
      initial 24 hours of admission to a community-based academic hospital. RESULTS: Of
      1,514 CTPAs, 125 were positive for VTE/PE yielding a positive diagnosis in 8.2%.
      Dyspnea was the most common symptom in patients and a normal physical exam was
      the most common finding. Among the 925 patients with adequate data to calculate
      the rate of contrast-induced nephropathy (CIN), 25.8% had an increase of at least
      25% in serum creatinine following the CTPA. Pre-existing diabetes and age were
      the most important predictors of CIN. CONCLUSIONS: CTPA has a low diagnostic
      yield for PE in a community setting, and in some patient populations, the rate of
      contrast-induced nephropathy may be higher than previously reported in the
      literature. Due to the retrospective nature of this study we were limited in
      using pre-test scoring systems and in measuring the impact of alternative CT
      diagnoses on patient management.

PMID- 23882363
TI  - Incidence of extreme hyperglycemia and hypoglycemia in hospitalized patients
      during the month of July in teaching hospitals.
AB  - INTRODUCTION: Blood glucose control has been found to be an important component
      in the care of hospitalized patients. Maintaining blood glucose within a target
      range using insulin intensively is a challenging task for physicians and requires
      skill and experience. We hypothesized that there may be more hyper- and
      hypoglycemia in July in teaching hospitals when new resident physicians begin
      their training. METHODS: We reviewed point-of-care blood glucose data from
      hospitalized patients at four community teaching hospitals for 2010. We defined
      severe hypoglycemia as blood glucose < 41 mg/dL and severe hyperglycemia as blood
      glucose > 399 mg/dL. Occurrence of hyper- and hypoglycemic events was assessed
      overall at the particular hospital globally and based on individual nursing
      units. Monthly occurrence rates were compared against the annual mean for that
      unit. RESULTS: The occurrence of hyper- and hypoglycemic events in July 2010 did
      not differ from the mean annual percentage of events at the applicable hospital.
      However, when the data were analyzed by the nursing unit, these extreme glucose
      events were significantly more common in 4 of the 11 units studied. Three of
      those four units were resident teaching units. CONCLUSIONS: These data suggest
      that there is some potential for increased risk of extreme hyper- and
      hypoglycemia at teaching hospitals in July, when new residents begin training.

PMID- 23882364
TI  - Non-traditional therapies for diabetes: fact or fiction.
AB  - The number of medications now available to treat Type 2 Diabetes has been
      expanding quickly over the past two decades. At the same time, the use of
      complementary and alternative medicine (CAM) has also been rising. Individuals
      with diabetes are 1.6 times more likely than those without diabetes to use
      modalities that are not considered part of conventional medicine. Numerous
      dietary supplements are available over the counter and are being advertized to
      treat diabetes and its co morbidities. No conclusive data on their clinical
      benefit, potential harms, dosing or interaction with other medications is yet
      available. But for clinicians to maintain a trusting relationship with their
      patient, a respectful non-confrontational attitude is needed to encourage open
      dialogue, provide accurate information, and facilitate changes to the medical
      regimen. It is essential that clinicians stay informed and advise their patient
      with the available scientific data accordingly. In this review, we focus on
      current data on six supplements commonly encountered in community practice for
      treating diabetes, including cinnamon, fenugreek, vinegar, ginseng, bitter melon,
      gymnema, chromium, and vanadium. 

PMID- 23882365
TI  - Pre-excitation syndrome: ablating the pathway.
AB  - Disappearance of a delta wave in a patient with pre-excitation is demonstrated
      following successful ablation. 

PMID- 23882366
TI  - In the SOAP: the Supplemental Offer and Acceptance Program (SOAP) from the
      perspective of a Community Hospital Residency.

PMID- 23882367
TI  - Imaging of carotid artery dissection.

PMID- 23882368
TI  - Preventing the inappropriate treatment of asymptomatic bacteriuria at a community
      teaching hospital.
AB  - The goal of this study was to assess the overtreatment of asymptomatic
      bacteriuria (ASB) in hospitalized patients, calculate the total costs of
      inappropriate treatment, and determine if a multi-faceted educational
      intervention was effective in reducing the overtreatment of ASB in a resource
      limited community hospital. The study encompassed three phases: a retrospective
      pre-intervention assessment of the baseline cost and treatment of ASB, the
      implementation of a multi-faceted educational intervention, and a prospective
      post-intervention assessment of the efficacy of the intervention. A positive
      urine culture was defined by bacterial counts >=10(5) cfu/mL. In the pre
      intervention group, 64 (83%) of 109 patients were asymptomatic: 30 (47%) were
      treated. In the post-intervention group, 13 (17%) of 55 patients were
      asymptomatic: 2 (15%) were treated, (p=0.04). Fewer urine cultures were collected
      during the post-intervention period than the pre-intervention period (3,127 and
      3,419, respectively) (p<0.001). The total cost of inappropriately treating ASB in
      the pre-intervention group was $1200 compared to $600 in the post-intervention
      group. The results demonstrated a significant decrease in the inappropriate
      treatment of ASB and the associated costs. 

PMID- 23882369
TI  - History of insulin.
AB  - The advancement of diabetes treatment has gone from crude extracts of insulin and
      accidental discovery of sulfa-like drugs in antibiotics to the development of
      drugs based on improved understanding of the pathophysiology of diabetes
      mellitus. This article will review the history of the discovery and development
      of insulin. A companion focusing on non-insulin diabetes agents will follow in
      the next issue of JCHIMP. 

PMID- 23882370
TI  - A case of probable non-familial early onset Alzheimer dementia in a Hispanic
      male.
AB  - BACKGROUND: Early onset Alzheimer's type dementia (EOAD) is usually familial and
      associated with mutations in the Presenilin-1 (PSEN1), Presenilin-2 (PSEN2) or
      amyloid precursor protein (APP) genes. It is rarely reported in patients of
      Hispanic descent. CASE REPORT: A 49-year-old Hispanic male developed significant
      cognitive impairment over a 4-year period. PET scan showed diminished metabolic
      activity in the posterior parietal/temporal lobes. Genetic testing revealed the
      presence of a PSEN1 gene mutation. CONCLUSION: Disparities in health care may
      account for an under-recognition of EOAD in the Hispanic population. Clinicians
      should test for EOAD in all patients with appropriate symptomatology, regardless
      of ethnicity. Early recognition and enrollment in clinical trials is vital to
      enhancing our understanding of the natural history and treatment of this
      condition.

PMID- 23882371
TI  - Vitamin C-induced oxalate nephropathy: a case report.
AB  - Therapeutic benefits of vitamin C is an area of active research and large doses
      have been suggested by many studies for treatment of various conditions. We are
      describing a case of oxalate nephropathy leading to end stage kidney disease,
      which occurred secondary to mega-dose of oral vitamin C. Increasing the awareness
      between medical personnel as well as patients will clearly decrease the incidence
      of this debilitating but, at the same time, highly preventable disease. 

PMID- 23882372
TI  - Anthrax: has the clinical milieu changed since 2001?
AB  - Since the anthrax attacks of 2001 (Amerithrax), several important improvements in
      the knowledge of Bacillus anthracis and the clinical condition it causes have
      occurred. While much remains to be known about the optimal management of anthrax
      patients, several approaches that were not widely utilized, available, or known
      in 2001 would be used in the treatment of critically ill anthrax patients in
      2012. 

PMID- 23882373
TI  - Splenic infarction associated with bacterial endocarditis and aortic valve
      vegetations.

PMID- 23882375
TI  - Hemolytic uremic syndrome and Clostridium difficile colitis.
AB  - Hemolytic uremic syndrome (HUS) can be associated with different infectious
      etiologies, but the relationship between pseudomembranous colitis and HUS was
      first described in the 1970s in some childhood patients. There is very limited
      published literature on Clostridium difficile-associated HUS. We report a case of
      C. difficile-related HUS in an adult patient and provide a review of the
      literature. 

PMID- 23882374
TI  - History of current non-insulin medications for diabetes mellitus.
AB  - This article is a brief review of the current non-insulin agents for diabetes
      mellitus in the United States, namely, sulfonylureas, biguanides,
      thiazolidinediones, meglitinides, alpha-glucosidase inhibitors, glucacon-like
      peptide-1 receptor agonists, dipeptidyl-peptidase-4 inhibitors, amylin agonists,
      bromocriptine, and colesevelam. 

PMID- 23882376
TI  - Intermittent left bundle branch block.
AB  - Presenting electrocardiograms of intermittent left bundle branch block in a 60
      year-old female. 

PMID- 23882377
TI  - Am I losing it?
AB  - Complaints of memory loss are frequent as one ages. Individuals worry about the
      presence of Alzheimer's disease, but the presence of other intact intellectual
      abilities is reassuring to these people. We do not know the cause of Alzheimer's
      disease. There are now 5.4 million confirmed cases in the United States. We know
      that the disease is an age-related, non-reversible brain disorder that develops
      over many years. Investigation is helped with the use of structural imaging
      (magnetic resonance imaging or computed tomography). Functional imaging is also
      valuable. Therapy for the problem involves various drugs; these help but do not
      cure the difficulty. 

PMID- 23882378
TI  - Cryptococcus infection in a non-HIV patient: a case report.
AB  - Cryptococcal infections are fungal infections most commonly seen in
      immunocompromised patients. Chronic high-dose steroid may precipitate such an
      immunocompromised state and thus create susceptibility to fungal infections.
      Cryptococcus neoformans is a saprophyte usually found in soil contaminated with
      pigeon droppings. Suspicion to diagnose begins with clinical symptoms that can be
      non-specific such as fevers, cough, and headaches. We present a case of steroid
      induced cryptococcal infection in a non-HIV-infected person. 

PMID- 23882379
TI  - Peer review.

PMID- 23882380
TI  - Be aware of wires in the veins: a case of superior vena cava syndrome in a
      patient with permanent pacemaker.
AB  - Superior vena cava (SVC) syndrome is an unusual complication of pacemaker and
      implantable cardioverter-defibrillator implantation. It is believed to be due to
      SVC thrombosis with or without stenosis induced by endothelial disruption from
      repeated mechanical trauma by the leads. A 58-year-old man presented with gradual
      swelling of his face, neck, and upper extremities of 10 days duration. A
      pacemaker had been implanted for symptomatic bradycardia over 5 years ago. Venous
      Doppler and venogram revealed thrombosis and stenosis of the SVC. He was treated
      with multimodal therapy and was discharged with complete resolution of his
      symptoms. 

PMID- 23882381
TI  - Pott's disease: a case of Mycobacterium xenopi infection of the spine.
AB  - Pott's disease is an infection of the spine with Mycobacterium tuberculosis that
      causes destruction of the spine elements resulting in progressive kyphosis. We
      are describing a rare case of Pott's disease where Mycobacterium xenopi was the
      inculpated organism. 

PMID- 23882382
TI  - Maintenance of certification in Internal Medicine: participation rates and
      patient outcomes.
AB  - The clinical practice of internal medicine continues to evolve with the addition
      of new information and new technology. Most internists in practice will have
      erosion of their knowledge after they complete training unless life-long learning
      occurs. The American Board of Internal Medicine (ABIM) began to issue time
      limited certification in 1990 and asserts that the Maintenance of Certification
      (MOC) program promotes the professional development of internists. However, the
      available medical literature does not provide strong support for the assumption
      that internists with certification or recertification have better patient
      outcomes. This relationship between recertification and patient outcomes needs
      more study. In addition, the participation in the Maintenance of Certification
      program by internists with lifetime certifications has been low, and
      recertification by leaders in internal medicine has also been relatively low.
      Some physicians in practice have concerns about the relevance of the program and
      the cost. Our review suggests that the ABIM needs to review its current
      Maintenance of Certification program and make changes to enhance its clinical
      relevance and educational value. We suggest that professional development should
      be based on focused reviews of the current literature, which is immediately
      relevant to clinical practice, and that recertification could be based on
      completion of modules and more frequent, less onerous testing. 

PMID- 23882383
TI  - Tackling the readmission epidemic: a resident teaching service perspective.
AB  - BACKGROUND: Readmission rates are projected to serve as quality measures that
      have the potential to negatively impact hospital and physician reimbursement.
      Individual physicians and hospitals are developing plans to reduce readmission
      rates. Successful plans should be based on specific data obtained from each
      individual type of practice. OBJECTIVE: To analyze the etiological factors
      responsible for readmissions to various teaching services in a community
      hospital. This will serve to identify potentially correctable factors that will
      be the basis for developing practice-specific plans to reduce readmissions.
      DESIGN: Retrospective detailed chart review. SETTING: Community teaching hospital
      affiliated with a large academic health care system. PARTICIPANTS: Patients
      admitted to teaching services at a community hospital. MEASUREMENTS: Data are
      presented as descriptive analysis. RESULTS: Advanced chronic medical conditions
      (31%), patients' lifestyle choices (28%), and new unrelated diagnoses (21%) are
      the major causes of readmissions. The remaining small percentage of readmissions
      is attributed to premature discharge, poor discharge planning, poor post
      discharge follow-up, medication errors, and failure to implement medical care
      guidelines. LIMITATIONS: Retrospective study from a single center. CONCLUSIONS:
      Causes of readmission are diverse. Although most are universal, the relative
      contribution of each factor is unique to each population. Institutions should
      generate their own data in order to direct their resources toward 'high return'
      areas. Current studies emphasize the role of physicians and health systems in
      reducing readmission rates. However, the area of readmissions related to
      patients' behaviors is not well explored. Our study identified the role of
      patients' lifestyle choices as a major cause of readmission.

PMID- 23882384
TI  - A review of common methods to convert morphine to methadone.
AB  - When dosed appropriately on carefully chosen patients, methadone can be a very
      safe and effective choice in managing chronic pain. Many authors have discussed
      important issues surrounding patient selection, drug interactions, screening for
      QTc prolongation and monitoring. This article will focus on the dosing dilemma
      that exists after the patient is deemed an appropriate candidate for methadone
      and a conversion is necessary from another opioid. Despite many publications
      dedicated to addressing this challenging topic, there is no consensus on the most
      appropriate method for converting an opioid regimen to methadone. Given the lack
      of concrete guidance, clinicians in a community setting are likely to be faced
      with an increased challenge if there are no available pain specialists to provide
      clinical support. Common methods for converting morphine to methadone will be
      reviewed and two clinical patient scenarios used to illustrate the outcomes of
      applying the methods. 

PMID- 23882385
TI  - Postoperative thrombotic thrombocytopenic purpura after aortofemoral bypass.
AB  - Thrombotic thrombocytopenic purpura (TTP) is uncommon in the postoperative
      setting, even more so after vascular surgery. We present a case of
      thrombocytopenia after aortofemoral bypass, which highlights the importance of a
      high index of suspicion for postoperative TTP to avoid life-threatening
      consequences. 

PMID- 23882386
TI  - Congenital complete heart block in a 71-year old.
AB  - A case of a 71-year-old male with congenital complete heart block is discussed.
      Patient remained asymptomatic with stable electrocardiograms. 

PMID- 23882387
TI  - Journal of community hospital internal medicine perspectives second anniversary.

PMID- 23882388
TI  - Are we training residents to communicate with low health literacy patients?
AB  - INTRODUCTION: A third of Americans have low health literacy (HL). Research
      indicates a significant knowledge and skills gap among residents pertaining to
      management of patients with low HL. OBJECTIVES: The objective of this study was
      to assess the teaching and evaluation methods around HL in community-based
      internal medicine residency programs. In addition, the study compared the
      teaching and evaluation practices used for doctor-patient communication skills to
      those used for HL skills. METHOD: A structured questionnaire was completed by
      faculty of community-based internal medicine residency programs through the
      'Community Hospital Education and Research Network' website and the Association
      of Program Directors in Internal Medicine community hospital assembly meeting in
      October 2011. RESULTS: Less than 50% of the programs provided any formal teaching
      on HL. HL was primarily taught via didactics (75%) followed by clinical
      observation (42%) and role-playing (25%). On the contrary, patient-provider
      communication skills were taught primarily using clinical observations (90%) and
      standardized patients (46.7%). The HL dimensions that programs focused on were
      the use of teach-back technique (100%), prevalence of low HL (83.3%), association
      between low HL and patient outcomes (83.3%), and use of plain language (83.3%).
      The areas that were least taught included helping patients navigate the health
      system (33.3%) and choosing effective written material for low HL patients (50%).
      CONCLUSION: Health literacy is not being taught consistently as part of the core
      curricula of the community-based internal medicine residency programs. There is a
      need for professional and technical resources to incorporate HL teaching in their
      curricula. There is a wide variation in terms of how HL skills are being taught
      and evaluated by community-based internal medicine residency programs.

PMID- 23882389
TI  - Thirty years of blackouts: a case report of swallow syncope.
AB  - Deglutition syncope has been demonstrated in isolated case reports, the first
      being described over 50 years ago. It is thought to be caused by a hypersensitive
      vagotonic reflex in response to esophageal dilation after swallowing. It can
      cause syncope due to complete atrioventricular (AV) block and acute reduction of
      cardiac output. Although rare, its lethality is worthy of discussion, as early
      recognition can offer complete treatment with placement of a pacemaker. A 54-year
      old man presented with 30 years of lightheadedness and syncope, followed by
      disorientation and tremors, after eating sandwiches or drinking carbonated
      beverages. He initially was evaluated by a neurologist. Work-up included cardiac
      2D transthoracic echocardiogram, electroencephalogram, swallow stud, pulmonary
      function tests, electrocardiogram, and cardiac stress testing. All tests were
      within normal limits, and it was determined that he was suffering from convulsive
      syncope and deglutition syncope. Referral to the cardiac electrophysiology
      department with tilt-table testing accompanied by swallow evaluation was then
      recommended. The tests demonstrated marked vagal response resulting in sinus
      bradycardia with second-degree AV block and pauses up to 3.5 seconds. Patient
      experienced near syncope. A rate-responsive, dual-chamber Boston Scientific
      pacemaker with DDDR programming was implanted. Patient has remained asymptomatic
      at follow-up. 

PMID- 23882390
TI  - An interventional pilot study on obesity among low-income patients using a
      computer-based weight management module.
AB  - Primary care physicians infrequently address lifestyle modification with their
      obese patients, among whom those of lower economic means are disproportionately
      represented. To enhance patients' access to education on lifestyle modification,
      a clinic-based computer kiosk was installed at our residency clinic for the
      purpose of healthy lifestyle education. While posttest scores improved and were
      maintained after completion of lifestyle modification education, body mass index
      (BMI) was essentially unaffected. Computer-based education without intensive
      counseling on lifestyle modification appears ineffective in reducing BMI amongst
      obese patients of lower economic means. Accountable care organization-sponsored
      health coaching may represent a potential means by which intensive counseling is
      accomplished among such patients. 

PMID- 23882391
TI  - Editor's notes.

PMID- 23882392
TI  - Diabetic myonecrosis: a diagnostic challenge in patients with long-standing
      diabetes.
AB  - A 51-year-old female with a history of type 1 diabetes mellitus (DM) presented
      with sudden onset of pain and swelling of the left thigh. Her initial evaluation
      revealed mildly elevated erythrocyte sedimentation rate and creatine
      phosphokinase. Venous and arterial Doppler studies were negative for DVT and
      arterial thrombus. Further imaging with CT scan and then MRI revealed an
      irregular, enhancing space-occupying lesion of the left upper and mid-thigh.
      Subsequent muscle biopsy showed myonecrosis and proliferative myositis. Both
      findings are consistent with diabetic myonecrosis, which is a microvascular
      complication of long-standing poorly controlled DM. The patient was treated with
      analgesics, supportive care, and optimization of glycemic control. While short
      term prognosis is good with adequate healing in a few weeks to several months,
      long-term prognosis is poor due to underlying extensive vascular disease.
      Although radiological findings are very suggestive of the diagnosis, most
      clinicians still need tissue biopsy to rule out other serious conditions such as
      infections and malignancy. 

PMID- 23882393
TI  - Parapneumonic empyema diagnosed by chest radiograph and computed tomography.
AB  - Pleural effusion is commonly seen associated with pneumonia. When this progresses
      to empyema, directed therapy is frequently required. Chest radiographic and
      computed tomography findings can help distinguish empyema from a transudative
      pleural effusion. 

PMID- 23882394
TI  - Shortness of breath after AV ablation: case of left phrenic nerve palsy.
AB  - Phrenic nerve palsy has been recognized as a complication of catheter ablation
      with a prevalence of 0.11-0.48% after atrial fibrillation ablation, independent
      of the type of ablation catheter or energy source, likely due to the anatomical
      relationship of the nerves. This report describes a case of new onset of
      shortness of breath (SOB) due to left diaphragm paralysis following transcatheter
      radiofrequency ablation in a patient with underlying chronic obstructive
      pulmonary disease. 

PMID- 23882395
TI  - Maintenance of Certification - important and to whom?

PMID- 23882396
TI  - The emperor's new clothes: hypersensitivity of the new cardiac isoenzymes.
AB  - Right ventricular (RV) myocardial infarction (MI) and pulmonary embolism (PE) are
      commonly recognized as two of the most challenging and vexing entities in
      clinical practice. When either is considered in a differential diagnosis, they
      warrant close consideration because of the life-threatening nature of these
      conditions. Their signs and symptoms overlap and, on rare occasions, they both
      can be simultaneously present in a single patient. Cardiac troponins are
      considered reliable markers of myocardial injury and are critical to the
      diagnosis of acute coronary syndromes. However, they can also be elevated in
      cases of PE. We herewith present a case of a woman who initially presented with
      syncope and then subsequently dyspnea. She manifested elevated cardiac
      isoenzymes, right-sided electrocardiogram abnormalities, and RV hypokinesis on
      echocardiography. She was initially diagnosed with RV infarct and managed with an
      interventional cardiology approach. However, her symptom of dyspnea persisted and
      the patient was eventually diagnosed with PE. Clinicians should entertain the
      diagnosis of PE in patients with elevated troponin I and evidence of right-sided
      cardiac compromise. 

PMID- 23882397
TI  - Complete esophageal obstruction following endoscopic variceal band ligation.
AB  - Variceal hemorrhage is a potential complication of portal hypertension. Besides
      medical management, endoscopic variceal band ligation (EVBL) has emerged as a
      promising prophylactic tool proving to be superior to sclerotherapy. EBVL is a
      simple procedure associated with minor complications and short recovery time. In
      this report, we present a case of a rare complication of complete esophageal
      obstruction following an EVBL procedure. Given the high numbers of such
      procedures performed, it is imperative that internists and specialists be aware
      of this unusual complication. 

PMID- 23882398
TI  - CT pulmonary angiography: an over-utilized imaging modality in hospitalized
      patients with suspected pulmonary embolism.
AB  - AIMS: To determine if computed tomographic pulmonary angiography (CTPA) was
      overemployed in the evaluation of hospitalized patients with suspected acute
      pulmonary embolism (PE). METHODS: Data were gathered retrospectively on
      hospitalized patients (n=185) who had CTPA for suspected PE between June and
      August 2009 at our institution. RESULTS: CTPA was done in 185 hospitalized
      patients to diagnose acute PE based on clinical suspicion. Of these, 30 (16.2%)
      patients were tested positive for acute PE on CTPA. The Well's pretest
      probability for PE was low, moderate, and high in 77 (41.6%), 83 (44.9%), and 25
      (13.5%) patients, respectively. Out of the 30 PE-positive patients, pretest
      probability was low in 2 (6.6%), moderate in 20 (66.7%), and high in 8 (26.6%)
      (p=0.003). Modified Well's criteria applied to all patients in our study revealed
      113 (61%) with low and 72 (39%) with high clinical pretest probability. When
      modified Well's criteria was applied to 30 PE-positive patients, 10 (33.3%) and
      20 (66.6%) were found to have low and high pretest probability, respectively
      (p=0.006). D-dimer assay was done in 30 (16.2%) of the inpatients with suspected
      PE and all of them were found to have elevated levels. A lower extremity duplex
      ultrasound confirmed deep venous thrombosis in 17 (9.1%) of the patients with
      suspected PE, at least 1 week prior to having CTPA. CONCLUSION: Understanding the
      recommended guidelines, evidence-based literature, and current concepts in
      evaluation of patients with suspected acute PE will reduce unnecessary CTPA
      examinations.

PMID- 23882399
TI  - Readmissions - a quality metric with financial penalties?

PMID- 23882400
TI  - Recurrent syncope, orthostatic hypotension and volatile hypertension: think
      outside the box.
AB  - The baroreceptors in the neck and aortic arch are important regulators of sudden
      blood pressure changes. They are innervated by CN IX and X and synapse in the
      brainstem. Baroreceptor failure is an under-recognized cause of recurrent
      syncope, orthostatic hypotension, and volatile hypertension, which is refractory
      to and may in fact worsen with conventional treatments. Baroreflex failure can be
      the result of neck and chest radiation, head and neck surgery, and
      cerebrovascular accidents involving the brainstem nuclei. The management of
      baroreflex failure is a challenge since patient education, lifestyle changes, and
      family support are extremely important in managing blood pressure. Leg exercises
      and Thrombo-Embolic Deterrent Stockings (TED) stockings are important in treating
      orthostatic hypotension. Clonidine is the antihypertensive of choice for supine
      hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic
      surges. We have encountered two patients with baroreflex failure after
      chemotherapy and radiation to the neck or upper chest. Temporal relationship
      between symptoms onset and the history of head, neck, and upper chest radiation
      or trauma is important in reaching a diagnosis. 

PMID- 23882401
TI  - Images in clinical medicine: Popeye's sign.

PMID- 23882402
TI  - Multiple myeloma: imaging evaluation of skeletal disease.
AB  - This patient is a 56-year-old woman with a history of IGG kappa multiple myeloma
      diagnosed 15 years prior to admission. She had widespread lytic bone lesions and
      pathological fractures, which remarkably had not been accompanied by significant
      pain, but were mostly refactory to chemotherapy. 

PMID- 23882404
TI  - Letter to the editor.

PMID- 23882403
TI  - Factors affecting adherence to evidence-based guidelines in the treatment of URI,
      sinusitis, and pharyngitis.
AB  - INTRODUCTION: Sinus infections, sore throats, and upper respiratory tract
      infections (URI) are common reasons patients seek medical care. Well-established
      treatment guidelines exist for prescribing antibiotics in these clinical
      scenarios, but are not often followed. OBJECTIVE: The objective of this study is
      to determine practice patterns related to prescribing antibiotics for sinusitis,
      URI, and pharyngitis. The main hypothesis is that attending physicians improve
      their adherence to antibiotic guidelines with a learner present. METHODS: A
      retrospective cohort study was performed on patients treated for URI, sinusitis,
      and pharyngitis at an ambulatory faculty practice. The use of relevant ICD-9
      codes from January 1, 2008 to January 30, 2012 resulted in 1,548 patient
      encounters which were reviewed for guideline adherence. Univariate analysis and
      multivariate logistic regression was performed for each outcome variable to
      determine if they influence antibiotic adherence. Variables studied were
      physician, presence of a learner, BMI, age, gender, day of the week, month,
      diabetes, immunosuppression, and COPD. RESULTS: Multivariate analysis showed the
      statistically significant variables were age (p=0.038) for pharyngitis and
      provider (p=0.013) for URI. There were no significant findings for sinusitis.
      Guideline adherence was 24% in patients with pharyngitis, 42% in acute sinusitis,
      79% in URI, and 57% overall. CONCLUSION: Guideline adherence varies depending on
      the treating physician and decreases when treating younger patients with
      pharyngitis. The presence of a learner did not improve prescribing habits. The
      reason for these findings remain unclear, but considerations for improvement
      could include following antibiotic adherence as a quality measure, giving
      patients handouts educating them about the impact of overprescribing antibiotics,
      and further education amongst faculty and residents about adhering to nationally
      recognized guidelines.

PMID- 23882405
TI  - Health literacy.

PMID- 23882406
TI  - Training community hospital residents for a future in the hospital's community -
      what program directors should know about Stark Laws.

PMID- 23882407
TI  - Pylephlebitis: a rare complication of an intra-abdominal infection.
AB  - Pylephlebitis is defined as an inflamed thrombosis of the portal vein. It is a
      rare complication of an intra-abdominal infection, and the diagnosis is often
      missed due to its nonspecific clinical presentation. Symptoms may include
      abdominal pain, fever, chills, fatigue, nausea, and vomiting. It is important to
      consider this differential when a patient presents with signs of abdominal sepsis
      since it has a high mortality rate and is often diagnosed postmortem.
      Pylephlebitis can be diagnosed via abdominal ultrasound or CT demonstrating a
      thrombus in the portal vein, and it must be treated early and aggressively with
      broad-spectrum antibiotics. We are presenting a case of pylephlebitis as well as
      discussing the diagnosis and treatment of this potentially lethal condition. 

PMID- 23882408
TI  - A case of apical ballooning syndrome in a male with status asthmaticus;
      highlighting the role of B2 agonists in the pathophysiology of a reversible
      cardiomyopathy.
AB  - Apical ballooning syndrome (ABS), also known as Takotsubo cardiomyopathy, was
      first reported by Dote and colleagues in Japanese literature in 1991 in a review
      of five cases. Case series have highlighted the association of severe
      psychological stressors as the major precipitating factors of this syndrome.
      Status Epilepticus and Sub-Arachnoid hemorrhage are also now established
      independent etiologies for this phenomenon in patients without coronary artery
      disease. We report a case of reversible apical ventricular dysfunction in a 50
      year-old male presenting with status asthmaticus who quickly underwent
      intubation. Following this, he had ST elevations in precordial leads with mild
      cardiac enzyme leak. Subsequent cardiac catheterization revealed a left
      ventricular ejection fraction of 25-30% with apical aneurismal segment. No
      obstructive disease was observed. Three days later there was marked clinical
      improvement; the patient was extubated and repeat echocardiography revealed a
      remarkable return to normal ventricular size and systolic function. Our case
      demonstrates that excess use of beta-agonists may be a potential risk factor for
      ABS and raises the possibility of cathecholamine cardiotoxicity being mediated
      via beta-receptors. Furthermore, it also negates the propensity of apical
      ballooning so far reported only in women with respiratory distress without
      confounding emotional stressors. 

PMID- 23882409
TI  - Stage-specific epigenetic gene silencing during thymocyte lineage commitment.
AB  - During lineage commitment, precursor cells must establish their signature gene
      expression programs to endow them with the requisite set of cellular functions.
      To maintain cellular identity, the gene expression program must be inherited
      stably by progeny of lineage-committed cells. Epigenetic regulation serves as a
      central mechanism to maintain such cellular memory. Although a lot of progress
      has been made in the last decade towards defining the spectrum of epigenetic
      modifications on histones and DNA, as well as the relevant enzymatic machinery,
      the mechanisms by which these modifiers are controlled during development remain
      poorly understood. Gene regulation at the Cd4 and Thpok loci provides ideal
      models for developmentally regulated gene silencing. A single transcriptional
      silencer at each locus establishes heritable, irreversible epigenetic silencing
      only in lineage-committed cells, whereas the same silencer elements establish a
      reversible repressive state in precursor cells. The dynamic versus permanent
      silencing of developmentally regulated loci by the stage-specific functions of
      silencers will be discussed in the context of cell lineage commitment. 

PMID- 23882410
TI  - At the Interface between Medical Informatics and Personalized Medicine: The
      eMERGE Network Experience.

PMID- 23882411
TI  - Trends in health information technology safety: from technology-induced errors to
      current approaches for ensuring technology safety.
AB  - OBJECTIVES: Health information technology (HIT) research findings suggested that
      new healthcare technologies could reduce some types of medical errors while at
      the same time introducing classes of medical errors (i.e., technology-induced
      errors). Technology-induced errors have their origins in HIT, and/or HIT
      contribute to their occurrence. The objective of this paper is to review current
      trends in the published literature on HIT safety. METHODS: A review and synthesis
      of the medical and life sciences literature focusing on the area of technology
      induced error was conducted. RESULTS: There were four main trends in the
      literature on technology-induced error. The following areas were addressed in the
      literature: definitions of technology-induced errors; models, frameworks and
      evidence for understanding how technology-induced errors occur; a discussion of
      monitoring; and methods for preventing and learning about technology-induced
      errors. CONCLUSIONS: The literature focusing on technology-induced errors
      continues to grow. Research has focused on the defining what an error is, models
      and frameworks used to understand these new types of errors, monitoring of such
      errors and methods that can be used to prevent these errors. More research will
      be needed to better understand and mitigate these types of errors.

PMID- 23882412
TI  - Potentiality of big data in the medical sector: focus on how to reshape the
      healthcare system.
AB  - OBJECTIVES: The main purpose of this study was to explore whether the use of big
      data can effectively reduce healthcare concerns, such as the selection of
      appropriate treatment paths, improvement of healthcare systems, and so on.
      METHODS: By providing an overview of the current state of big data applications
      in the healthcare environment, this study has explored the current challenges
      that governments and healthcare stakeholders are facing as well as the
      opportunities presented by big data. RESULTS: Insightful consideration of the
      current state of big data applications could help follower countries or
      healthcare stakeholders in their plans for deploying big data to resolve
      healthcare issues. The advantage for such follower countries and healthcare
      stakeholders is that they can possibly leapfrog the leaders' big data
      applications by conducting a careful analysis of the leaders' successes and
      failures and exploiting the expected future opportunities in mobile services.
      CONCLUSIONS: First, all big data projects undertaken by leading countries'
      governments and healthcare industries have similar general common goals. Second,
      for medical data that cuts across departmental boundaries, a top-down approach is
      needed to effectively manage and integrate big data. Third, real-time analysis of
      in-motion big data should be carried out, while protecting privacy and security.

PMID- 23882413
TI  - Nursing informatics: decades of contribution to health informatics.
AB  - OBJECTIVES: In this paper we present a contemporary understanding of "nursing
      informatics" and relate it to applications in three specific contexts, hospitals,
      community health, and home dwelling, to illustrate achievements that contribute
      to the overall schema of health informatics. METHODS: We identified literature
      through database searches in MEDLINE, EMBASE, CINAHL, and the Cochrane Library.
      Database searching was complemented by one author search and hand searches in six
      relevant journals. The literature review helped in conceptual clarification and
      elaborate on use that are supported by applications in different settings.
      RESULTS: Conceptual clarification of nursing data, information and knowledge has
      been expanded to include wisdom. Information systems and support for nursing
      practice benefits from conceptual clarification of nursing data, information,
      knowledge, and wisdom. We introduce three examples of information systems and
      point out core issues for information integration and practice development.
      CONCLUSIONS: Exploring interplays of data, information, knowledge, and wisdom,
      nursing informatics takes a practice turn, accommodating to processes of
      application design and deployment for purposeful use by nurses in different
      settings. Collaborative efforts will be key to further achievements that support
      task shifting, mobility, and ubiquitous health care.

PMID- 23882414
TI  - Role of computerized physician order entry usability in the reduction of
      prescribing errors.
AB  - OBJECTIVES: Some hospitals have implemented computerized physician order entry
      (CPOE) systems to reduce the medical error rates. However, research in this area
      has been very limited, especially regarding the impact of CPOE use on the
      reduction of prescribing errors. Moreover, the past studies have dealt with the
      overall impact of CPOE on the reduction of broadly termed "medical errors", and
      they have not specified which medical errors have been reduced by CPOE.
      Furthermore, the majority of the past research in this field has been either
      qualitative or has not used robust empirical techniques. This research examined
      the impacts of usability of CPOE systems on the reduction of doctors' prescribing
      errors. METHODS: One hundred and sixty-six questionnaires were used for
      quantitative data analyses. Since the data was not normally distributed, partial
      least square path modelling-as the second generation of multivariate data
      analyses-was applied to analyze data. RESULTS: It was found that the ease of use
      of the system and information quality can significantly reduce prescribing
      errors. Moreover, the user interface consistency and system error prevention have
      a significant positive impact on the perceived ease of use. More than 50% of the
      respondents believed that CPOE reduces the likelihood of drug allergy, drug
      interaction, and drug dosing errors thus improving patient safety. CONCLUSIONS:
      Prescribing errors in terms of drug allergy, drug interaction, and drug dosing
      errors are reduced if the CPOE is not error-prone and easy to use, if the user
      interface is consistent, and if it provides quality information to doctors.

PMID- 23882415
TI  - Lessons Learned from Development of De-identification System for Biomedical
      Research in a Korean Tertiary Hospital.
AB  - OBJECTIVES: The Korean government has enacted two laws, namely, the Personal
      Information Protection Act and the Bioethics and Safety Act to prevent the
      unauthorized use of medical information. To protect patients' privacy by
      complying with governmental regulations and improve the convenience of research,
      Asan Medical Center has been developing a de-identification system for biomedical
      research. METHODS: We reviewed Korean regulations to define the scope of the de
      identification methods and well-known previous biomedical research platforms to
      extract the functionalities of the systems. Based on these review results, we
      implemented necessary programs based on the Asan Medical Center Information
      System framework which was built using the Microsoft. NET Framework and C#.
      RESULTS: The developed de-identification system comprises three main components:
      a de-identification tool, a search tool, and a chart review tool. The de
      identification tool can substitute a randomly assigned research ID for a hospital
      patient ID, remove the identifiers in the structured format, and mask them in the
      unstructured format, i.e., texts. This tool achieved 98.14% precision and 97.39%
      recall for 6,520 clinical notes. The search tool can find the number of patients
      which satisfies given search criteria. The chart review tool can provide de
      identified patient's clinical data for review purposes. CONCLUSIONS: We found
      that a clinical data warehouse was essential for successful implementation of the
      de-identification system, and this system should be tightly linked to an
      electronic Institutional Review Board system for easy operation of honest
      brokers. Additionally, we found that a secure cloud environment could be adopted
      to protect patients' privacy more thoroughly.

PMID- 23882416
TI  - Information system success model for customer relationship management system in
      health promotion centers.
AB  - OBJECTIVES: Intensified competitiveness in the healthcare industry has increased
      the number of healthcare centers and propelled the introduction of customer
      relationship management (CRM) systems to meet diverse customer demands. This
      study aimed to develop the information system success model of the CRM system by
      investigating previously proposed indicators within the model. METHODS: THE
      EVALUATION AREAS OF THE CRM SYSTEM INCLUDES THREE AREAS: the system
      characteristics area (system quality, information quality, and service quality),
      the user area (perceived usefulness and user satisfaction), and the performance
      area (personal performance and organizational performance). Detailed evaluation
      criteria of the three areas were developed, and its validity was verified by a
      survey administered to CRM system users in 13 nationwide health promotion
      centers. The survey data were analyzed by the structural equation modeling
      method, and the results confirmed that the model is feasible. RESULTS:
      Information quality and service quality showed a statistically significant
      relationship with perceived usefulness and user satisfaction. Consequently, the
      perceived usefulness and user satisfaction had significant influence on
      individual performance as well as an indirect influence on organizational
      performance. CONCLUSIONS: This study extends the research area on information
      success from general information systems to CRM systems in health promotion
      centers applying a previous information success model. This lays a foundation for
      evaluating health promotion center systems and provides a useful guide for
      successful implementation of hospital CRM systems.

PMID- 23882417
TI  - Use of data mining techniques to determine and predict length of stay of cardiac
      patients.
AB  - OBJECTIVES: Predicting the length of stay (LOS) of patients in a hospital is
      important in providing them with better services and higher satisfaction, as well
      as helping the hospital management plan and managing hospital resources as
      meticulously as possible. We propose applying data mining techniques to extract
      useful knowledge and draw an accurate model to predict the LOS of heart patients.
      METHODS: Data were collected from patients with coronary artery disease (CAD).
      The patient records of 4,948 patients who had suffered CAD were included in the
      analysis. The techniques used are classification with three algorithms, namely,
      decision tree, support vector machines (SVM), and artificial neural network
      (ANN). LOS is the target variable, and 36 input variables are used for
      prediction. A confusion matrix was obtained to calculate sensitivity,
      specificity, and accuracy. RESULTS: The overall accuracy of SVM was 96.4% in the
      training set. Most single patients (64.3%) had an LOS <=5 days, whereas 41.2% of
      married patients had an LOS >10 days. Moreover, the study showed that comorbidity
      states, such as lung disorders and hemorrhage with drug consumption have an
      impact on long LOS. The presence of comorbidities, an ejection fraction <2, being
      a current smoker, and having social security type insurance in coronary artery
      patients led to longer LOS than other subjects. CONCLUSIONS: All three algorithms
      are able to predict LOS with various degrees of accuracy. The findings
      demonstrated that the SVM was the best fit. There was a significant tendency for
      LOS to be longer in patients with lung or respiratory disorders and high blood
      pressure.

PMID- 23882418
TI  - Modified mixture of experts for the diagnosis of perfusion magnetic resonance
      imaging measures in locally rectal cancer patients.
AB  - OBJECTIVES: This study demonstrates the feasibility of using a modified mixture
      of experts (ME) model with repeated measured tumoural K(trans) value to perform
      an automatic diagnosis of responder based on perfusion magnetic resonance imaging
      (MRI) of rectal cancer. METHODS: The data used in this study was obtained from 39
      patients with primary rectal carcinoma who were scheduled for preoperative
      chemoradiotherapy. The modified ME model is a joint modeling of the ME model via
      the linear mixed effect model. First, we considered two local experts and a
      gating network, and the modified expert network as a liner mixed effect model.
      Afterward, the finding estimates were obtained via the expectation-maximization
      algorithm. All computation was performed by R-2.15.2. RESULTS: We found that two
      experts have different patterns. The feature of expert 1 (n = 10) had a higher
      baseline value and a lower slope than expert 2 (n = 29). A comparison of the
      estimated experts and responder/non-responder groups according to T-downstaging
      criteria showed that expert 1 had a more effect treatment responder than expert
      2. CONCLUSIONS: A novel feature of this study is that it is an extension of
      classical ME models in case of repeatedly measured data. The proposed model has
      the advantages of flexibility and adaptability for identifying distinct subgroups
      with various time patterns, and it can be applied to biomedical data which is
      measured repeatedly, such as time-course microarray data or cohort data. This
      method can assist physicians as important diagnostic decision making mechanism.

PMID- 23882419
TI  - Computational approach for protein structure prediction.
AB  - OBJECTIVES: To predict the structure of protein, which dictates the function it
      performs, a newly designed algorithm is developed which blends the concept of
      self-organization and the genetic algorithm. METHODS: Among many other
      approaches, genetic algorithm is found to be a promising cooperative
      computational method to solve protein structure prediction in a reasonable time.
      To automate the right choice of parameter values the influence of self
      organization is adopted to design a new genetic operator to optimize the process
      of prediction. Torsion angles, the local structural parameters which define the
      backbone of protein are considered to encode the chromosome that enhances the
      quality of the confirmation. Newly designed self-configured genetic operators are
      used to develop self-organizing genetic algorithm to facilitate the accurate
      structure prediction. RESULTS: Peptides are used to gauge the validity of the
      proposed algorithm. As a result, the structure predicted shows clear improvements
      in the root mean square deviation on overlapping the native indicates the overall
      performance of the algorithm. In addition, the Ramachandran plot results implies
      that the conformations of phi-psi angles in the predicted structure are better as
      compared to native and also free from steric hindrances. CONCLUSIONS: The
      proposed algorithm is promising which contributes to the prediction of a native
      like structure by eliminating the time constraint and effort demand. In addition,
      the energy of the predicted structure is minimized to a greater extent, which
      proves the stability of protein.

PMID- 23882420
TI  - Research progress in the radioprotective effect of the canonical Wnt pathway.
AB  - Irradiation from diverse sources is ubiquitous and closely associated with human
      activities. Radiation therapy (RT), an important component of multiple radiation
      origins, is a common therapeutic modality for cancer. More importantly, RT
      provides significant contribution to oncotherapy by killing tumor cells. However,
      during the course of therapy, irradiation of normal tissues can result in a wide
      range of side effects, including self-limited acute toxicities, mild chronic
      symptoms, or severe organ dysfunction. Although numerous promising
      radioprotective agents have emerged, only a few have successfully entered the
      market because of various limitations. At present, the widely accepted hypothesis
      for protection against radiation-caused injury involves the Wnt canonical
      pathway. Activating the Wnt/beta-catenin signaling pathway may protect the
      salivary gland, oral mucosa, and gastrointestinal epithelium from radiation
      damage. The underlying mechanisms include inhibiting apoptosis and preserving
      normal tissue functions. However, aberrant Wnt signaling underlies a wide range
      of pathologies in humans, and its various components contribute to cancer.
      Moreover, studies have suggested that Wnt/beta-catenin signaling may lead to
      radioresistance of cancer stem cell. These facts markedly complicate any
      definition of the exact function of the Wnt pathway. 

PMID- 23882421
TI  - A survey and evaluation of population-based screening for gastric cancer.
AB  - Screening and early diagnosis of gastric cancer play important roles in reducing
      the mortality of gastric cancer. A vast amount of study data on gastric cancer
      screening and early diagnosis has been accumulated in and out of China in the
      past decades. The practice of gastric cancer screening has also been efficiently
      carried out in different countries and regions. However, no widely accepted
      principle of population screening for gastric cancer has been developed yet.
      Screening for gastric cancer requires extensive exploration both theoretically
      and practically. This article focuses on the method and program of gastric cancer
      screening based on population. Moreover, the current situation of gastric cancer
      screening and its evaluation are evaluated. 

PMID- 23882422
TI  - Detection of D2-40 monoclonal antibody-labeled lymphatic vessel invasion in
      esophageal squamous cell carcinoma and its clinicopathologic significance.
AB  - OBJECTIVE: This study aims to investigate the clinicopathologic significance of
      lymphatic vessel invasion (LVI) labeled by D2-40 monoclonal antibody in
      esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical assay was
      used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the
      correlation between the clinicopathologic feature and the overall survival time
      of the patients was analyzed. RESULTS: The lymph node metastasis rates were 70%
      and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal
      metastasis rate was higher in the LVI-positive group than in the LVI-negative
      group. Multivariate regression analysis showed that LVI was related to nodal
      metastasis (P<0.001). The median survival time of the patients was 26 and 43
      months in the LVI-positive and LVI-negative groups, respectively. Although
      univariate regression analysis showed significant difference between the two
      groups (P=0.014), multivariate regression analysis revealed that LVI was not an
      independent prognostic factor for overall survival in the ESCC patients
      (P=0.062). Lymphatic node metastasis (P=0.031), clinical stage (P=0.019), and
      residual tumor (P=0.026) were the independent prognostic factors. CONCLUSION: LVI
      labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node
      metastasis in ESCC patients.

PMID- 23882423
TI  - Clinicopathologic characteristics and prognostic factors of 63 gastric cancer
      patients with metachronous ovarian metastasis.
AB  - OBJECTIVE: This study aims to explore the clinicopathologic characteristics and
      prognostic factors of gastric cancer patients with metachronous ovarian
      metastasis. METHODS: Clinicopathologic data were collected from 63 post-operative
      gastric cancer patients with metachronous ovarian metastasis. The patients were
      admitted to the Cancer Institute and Hospital, Chinese Academy of Medical Science
      and Peking Union Medical College between January 1999 and December 2011. A log
      rank test was conducted for survival analysis. Possible prognostic factors that
      affect survival were examined by univariate analysis. A Cox regression model was
      used for multivariate analysis. RESULTS: The incidence of ovarian metastasis was
      3.4% with a mean age of 45 years. Up to 65.1% of the patients were pre
      menopausal. The mean interval between ovarian metastasis and primary cancer was
      16 months. Lowly differentiated carcinoma ranked first in the primary gastric
      cancers. The majority of lesions occurred in the serous membrane (87.3%). The
      metastatic sites included N2-3 lymph nodes (68.3%), bilateral ovaries (85.7%),
      and peritoneal membrane (73%). Total resection of metastatic sites was performed
      (31.7%). The overall median survival was 13.6 months, whereas the overall 1-, 2-,
      and 3-year survival rates were 52.5%, 22.0%, and 9.8%, respectively. The 5-year
      survival rate was zero. Univariate analysis showed that the patient prognosis was
      correlated with metastatic peritoneal seeding, vascular tumor embolus, range of
      lesion excision, and mode of comprehensive treatment with adjuvant chemotherapy
      (P<0.05). Multivariate analysis indicated that metastatic peritoneal seeding was
      an independent prognostic factor for gastric cancer patients with ovarian
      metastasis (P<0.01). CONCLUSION: Effective control of peritoneal seeding-induced
      metastasis is important for improving the prognosis of gastric cancer patients
      with ovarian metastasis.

PMID- 23882424
TI  - Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer.
AB  - OBJECTIVE: Chemotherapy is the standard treatment for small-cell lung cancer
      (SCLC), and leukopenia is a common side effect. This study assesses whether
      chemotherapy-induced leukopenia is a predictor of efficacy and whether it is
      associated with the survival of SCLC patients. METHODS: A retrospective analysis
      was conducted on data from 445 patients with SCLC who received standard
      chemotherapy for 4 to 10 cycles. The World Health Organization grading system
      classifies leukopenia during chemotherapy as follows: absent (grade 0), mild
      (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall
      survival (OS). RESULTS: The association between chemotherapy-induced leukopenia
      and OS was assessed. According to a multivariate Cox model with time-varying
      covariates, the hazard ratio of death was significantly lower among patients with
      mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to
      0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13
      months (95% CI: 11 to 15 months) for patients who did not experience leukopenia,
      17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months
      (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs.
      severe leukopenia, P=0.047). CONCLUSION: Leukopenia during chemotherapy is
      associated with the survival of SCLC patients. Mild leukopenia is strongly
      associated with longer survival time.

PMID- 23882425
TI  - Preoperative intestinal stent decompression with primary laparoscopic surgery to
      treat left-sided colorectal cancer with obstruction: a report of 21 cases.
AB  - OBJECTIVE: This work aimed to study the safety and efficacy of preoperative
      intestinal stent decompression combined with laparoscopic surgery to treat left
      sided colorectal cancer with obstruction (LCCO). METHODS: Retrospective analysis
      was conducted on data obtained from 21 LCCO patients admitted to The First
      Affiliated Hospital of Zhejiang Chinese Medicine University during March 2008 and
      December 2011. To remove the intestinal obstruction, preoperative intestinal
      stent placement under colonoscopic guidance was performed. Approximately 7 to 10
      days after the operation, laparoscopic radical surgery of colorectal cancer was
      conducted. RESULTS: Among the 21 cases studied, laparoscopic surgery was
      successful in 20 patients. Emergent laparotomy was conducted in one patient
      because of tumor invasion in the ureter. The duration of the operation ranged
      from 180 to 320 min, and the average time was 220 min. The recovery time for
      bowel function ranged from 2 to 5 days with an average time of 3 days.
      Postoperative infection of the incision occurred in one case. No anastomotic
      leakage was observed in any of the cases. CONCLUSION: Preoperative intestinal
      stent decompression, combined with primary stage laparoscopic surgery, is a safe
      and effective method for the treatment of LCCO.

PMID- 23882426
TI  - Modified frontolateral partial laryngectomy operation: combined muscle-pedicle
      hyoid bone and thyrohyoid membrane flap in laryngeal reconstruction.
AB  - OBJECTIVE: Laryngeal reconstruction is needed to preserve laryngeal function in
      patients who have undergone extensive vertical or frontal partial laryngectomy.
      However, the procedure remains a difficult challenge. Several reconstruction
      techniques have been described, but these techniques pose risks of complications
      such as laryngeal stenosis. This study aimed to evaluate the postoperative course
      and functional outcomes of a new technique that combined a muscle-pedicle hyoid
      bone and a thyrohyoid flap during laryngeal reconstruction after tumor resection.
      METHODS: Four patients underwent extensive vertical partial or frontal partial
      laryngectomy for cancer. After tumor resection, laryngeal reconstruction was
      performed using the proposed technique. Postoperative recovery time,
      complications, and oncologic results were evaluated. RESULTS: The four patients
      were successfully treated with the proposed technique. No dyspnea, dysphagia, or
      death occurred during the postoperative course. Decannulation was performed after
      a median of 3 days. The average postoperative hospital stay was 7 days. Short
      term postoperative functional recovery was normal. No laryngeal stenosis or tumor
      recurrence was observed in any of the four patients after a follow-up period of
      more than 24 months. CONCLUSION: The combination of the muscle-pedicle hyoid bone
      and the thyrohyoid flap is a reliable procedure for laryngeal reconstruction
      after extensive vertical partial or frontal partial laryngectomy.

PMID- 23882427
TI  - Surgical management of non-parasitic hepatic cyst with biliary communication: a
      case report.
AB  - Non-parasitic hepatic cysts with biliary communication are rare. The clinical
      symptoms involved are not specific to this condition, thereby making diagnosis
      difficult and treatment controversial. Here, we report a case of 70-year-old
      woman complaining of abdominal satiety, combined with non-specific pain in the
      right upper quadrant. The abdominal contrast-enhanced MRI-scan revealed a large
      and thick-walled septus cystic lesion in the liver. During operation, the biliary
      fistula was confirmed in the cyst cavity. A silica gel tube was inserted via the
      cystic duct for cholangiography, which demonstrated communication between the
      cyst and biliary tract. We performed wide-scale cyst wall resection; the biliary
      fistula was completely repaired by the closure of communicated bile ducts. The
      postoperative course was uneventful, and the patient was discharged with no sign
      of cholangitis or any other symptoms. The novel surgical management via wide
      resection of the cyst wall and closure of biliary communication proved to be an
      adequate and effective procedure for treating nonparasitic hepatic cysts with
      biliary communication. 

PMID- 23882428
TI  - Splenectomy for splenic metastases from malignant adrenal pheochromocytoma: a
      case report.
AB  - Splenic metastasis is generally not a common clinical event. However, metastasis
      to the spleen from adrenal pheochromocytoma is extremely rare and has not been
      reported in literature. This report presents a case of a 58 year-old male patient
      who developed spleen-only metastases in July 2007. The patient had a previous
      history of left epinephroectomy for adrenal pheochromocytoma in January 2003.
      Abdominal computed tomography demonstrated multiple enhancing lesions suggestive
      of metastases; thus splenectomy was performed. Pathological examinations
      confirmed the diagnosis of splenic metastases from pheochromocytoma. The patient
      was alive without recurrence 48 months after splenectomy. This study is the first
      report on splenic metastasis from previous adrenal pheochromocytoma, and long
      term survival was achieved by splenectomy. A history of malignancy indicates a
      high index of suspicion for splenic metastasis, and long-term survival can be
      achieved by splenectomy for spleen-only metastasis. 

PMID- 23882429
TI  - An exceptional case of myelodysplastic syndrome with myelofibrosis following
      combination chemotherapy for squamous cell lung cancer.
AB  - A 60-year-old woman with squamous cell carcinoma in the right lung was
      successfully treated with four cycles of combination chemotherapy after surgery,
      and complete remission was achieved. However, the patient developed
      myelodysplastic syndrome (MDS) RAEB-2 with myelofibrosis after remission,
      possibly because of chemotherapy or DNA methylation. The patient responded well
      to dacitabine (Dacogen), suggesting that DNA hypomethylation agents can be a
      promising therapy to retard the progression of a second tumor or carcinoma. 

PMID- 23882431
TI  - Study Site Experiences and Attitudes Toward Prospective Assessments of Suicidal
      Ideation and Behavior in Clinical Trials: Results of an Internet-based Survey.
AB  - OBJECTIVE: The International Society for CNS Clinical Trials and Methodology
      Suicidal Ideation and Behavior Assessment Working Group conducted an online
      survey regarding clinical trial site experiences and attitudes toward suicidal
      ideation and behavior data collection following the 2010 release of the initial
      United States Food and Drug Administration draft guidance on prospective
      assessment of suicidal ideation and behavior in clinical trials. Sites that had
      participated in at least one central nervous system clinical trial in the prior
      two years (N=6,058) were invited, via email, to complete a 20-item online
      assessment survey. RESULTS: Nine hundred and seventy-nine evaluable responses
      were collected (42% United States). Respondents included principal investigators
      (36%), raters (28%), coordinators (25%), and others (10%). The majority were
      psychiatrists (43%) and reported using suicidal ideation and behavior assessments
      across many indications. Most respondents (80%) personally conducted suicidal
      ideation and behavior assessments. Overall, respondents indicated that suicidal
      ideation and behavior assessments were readily incorporated into the conduct of
      clinical trials and improved subject safety. The greatest challenge was obtaining
      an accurate baseline lifetime history (51%), while the greatest benefit was
      identifying subjects at risk of suicide (84%). Approximately a quarter of
      respondents reported implementation challenges such as training. Differences
      based on geographical region, respondents' roles, and responsibility for
      assessments were observed. Open-ended responses revealed additional challenges,
      e.g., use in cognitively impaired populations. CONCLUSION: Prospective suicidal
      ideation and behavior monitoring was generally viewed positively, though specific
      challenges were identified. Limitations include self-report survey methodology
      and recruitment of only central nervous system clinical trials sites. These
      findings may help guide development of better methodologies for suicidal ideation
      and behavior assessment in clinical trials.

PMID- 23882432
TI  - How can registries contribute to the development and evaluation of CNS
      therapeutics?
AB  - This article is based on the proceedings from a workshop held during the Autumn
      2011 International Society for CNS Clinical Trials and Methodology (ISCTM)
      Conference in Amelia Island, Florida. The goal of the workshop was to establish
      preliminary steps in determining whether and how patient registries can augment
      clinical trials in the field of central nervous system therapeutics. Participants
      in the workshop first defined several different types of registries and then
      created a list of questions that should be addressed in order to determine how
      registries might be used. The workshop concluded with discussion on logistical
      and practical considerations regarding use of patient registries. 

PMID- 23882433
TI  - Defining a clinically meaningful effect for the design and interpretation of
      randomized controlled trials.
AB  - OBJECTIVE: This article captures the proceedings of a meeting aimed at defining
      clinically meaningful effects for use in randomized controlled trials for
      psychopharmacological agents. DESIGN: Experts from a variety of disciplines
      defined clinically meaningful effects from their perspectives along with
      viewpoints about how to design and interpret randomized controlled trials.
      SETTING: The article offers relevant, practical, and sometimes anecdotal
      information about clinically meaningful effects and how to interpret them.
      PARTICIPANTS: The concept for this session was the work of co-chairs Richard
      Keefe and the late Andy Leon. Faculty included Richard Keefe, PhD; James McNulty,
      AbScB; Robert S. Epstein, MD, MS; Shelby D. Reed, PhD; Juan Sanchez, MD; Ginger
      Haynes, PhD; Andrew C. Leon, PhD; Helena Chmura Kraemer, PhD; Ellen Frank, PhD,
      and Kenneth L. Davis, MD. RESULTS: The term clinically meaningful effect is an
      important aspect of designing and interpreting randomized controlled trials but
      can be particularly difficult in the setting of psychopharmacology where effect
      size may be modest, particularly over the short term, because of a strong
      response to placebo. Payers, regulators, patients, and clinicians have different
      concerns about clinically meaningful effects and may describe these terms
      differently. The use of moderators in success rate differences may help better
      delineate clinically meaningful effects. CONCLUSION: There is no clear consensus
      on a single definition for clinically meaningful differences in randomized
      controlled trials, and investigators must be sensitive to specific concerns of
      stakeholders in psychopharmacology in order to design and execute appropriate
      clinical trials.

PMID- 23882434
TI  - Aripiprazole withdrawal: a case report.

PMID- 23882435
TI  - Valproate-induced hyperammonemic encephalopathy: a case report.

PMID- 23882436
TI  - Systematic Study of Structured Diagnostic Procedures in Outpatient Psychiatric
      Rehabilitation: A Three-year, Three-cohort Study of the Stability of Psychiatric
      Diagnoses.
AB  - Background. Psychiatric diagnoses are important for treatment planning. There are
      a number of current challenges in the area of psychiatric diagnosis with
      important treatment implications. In this study, we examined the differential
      usefulness of two semi-structured interviews of differing length compared to
      clinical diagnoses for generation of diagnoses that did not require modification
      over the course of treatment. Methods. We performed a three-year, three-cohort
      study at an outpatient psychiatric rehabilitation facility, comparing the
      stability of admission diagnoses when generated by unstructured procedures
      relying on referring clinician diagnosis, the SCID, and the MINI. We examined
      changes in diagnoses from admission to discharge (averaging 13 weeks) and, during
      the second two years, convergence between referring clinician diagnoses and those
      generated by structured interviews. The same three interviewers examined all
      patients in all three phases of the study. Results. Admission and discharge
      diagnoses were available for 313 cases. Diagnoses generated with the unstructured
      procedure were changed by discharge 74 percent of the time, compared to four
      percent for SCID diagnoses and 11 percent for MINI diagnoses. Referring clinician
      diagnoses were disconfirmed in Years 2 and 3 in 56 percent of SCID cases and 44
      percent of MINI cases. The distinctions between unipolar and bipolar disorders
      were particular points of disagreement, with similar rates of under and over
      diagnosis of bipolar disorder. The rate of confirmation of referring clinician
      diagnoses of schizoaffective disorder was 10 percent with the SCID and 11 percent
      with the MINI. Discussion. In this setting, there appears to be a reasonable
      trade-off between brevity and accuracy through the use of the MINI compared to
      the SCID, with substantial improvements in stability of diagnoses compared to
      clinician diagnoses. Clinical diagnoses were minimally overlapping with the
      results of structured diagnoses, suggesting that structured assessment,
      particularly early in the illness or in short term treatment settings, may
      improve treatment planning. 

PMID- 23882437
TI  - Sialorrhea and aspiration pneumonia: a case study.
AB  - This case study compares two different clinical outcomes for a patient with a
      long-standing psychotic disorder prescribed clozapine on two occasions. During
      the first trial, clozapine was used at a higher dose for this patient (350
      450mg/day) and included clinically significant sialorrhea, pneumonia, and
      pneumonia-like illnesses requiring immediate medical intervention including
      hospitalization. There were also patient complaints of fatigue, cough, choking,
      and constipation leading to poor adherence. Clozapine was discontinued when the
      patient withdrew his consent due to side effects, despite his awareness of its
      benefits, including reduction of command hallucinations and irritability. The
      second clozapine trial was associated with lower daily doses and therapeutic
      serum blood levels. The patient was actively participating in and adhering to the
      medication plan. A very narrow window of clozapine dose was exceeded for two days
      and the patient complained of hypersalivation, cough, and lethargy. He was
      subsequently hospitalized for a two week period to treat aspiration pneumonia.
      This hospitalization helped establish the ideal daily dose of clozapine for this
      patient and also brought the relationship between aspiration pneumonia and
      clozapine to the attention of the psychiatrist and medical specialist. Once the
      appropriate dosage for this patient was established, his psychotic and affective
      symptoms were controlled, he was not hampered by adverse side effects, and he
      started to actively participate in social and recreational activities and plans
      that culminated in discharge from a state psychiatric facility to a supportive
      community residence. It is our hope that the lessons we have learned from our
      shared experience with this patient will be of benefit to other clinicians and
      patients. 

PMID- 23882438
TI  - A probable case of peduncular hallucinosis secondary to a cerebral peduncular
      lesion successfully treated with an atypical antipsychotic.
AB  - Peduncular hallucinosis is a rare phenomenon that has been reported in case
      reports and case series. The exact pathophysiology is unclear, but is postulated
      to involve disruption and dysregulation of the visual neuronal pathways in the
      brain. A case of complex visual hallucinations in an elderly man with no previous
      history of psychosis is discussed. Magnetic resonance imaging of the patient's
      brain revealed a discrete peduncular lesion that was the likely cause of the
      hallucinations. The lesion was not present on a previous brain magnetic resonance
      imaging that predated the onset of the hallucinations. The patient was started on
      low-dose risperidone, which resulted in the complete resolution of the visual
      hallucinations. It is important to consider discrete rostral brainstem lesions as
      a potential cause of new onset visual hallucinations in patients being evaluated
      for visual hallucinations. 

PMID- 23882439
TI  - Clinical implications of the new diagnostic guidelines for dementia.
AB  - New criteria have been proposed for diagnosing Alzheimer's disease. These
      emphasize that this illness exists on a continuum and begins early on. This
      article reviews the pros and cons of these criteria. It also provides practical
      guidelines for psychiatrists whose patients may be affected by these new
      criteria. Particular attention is given to patients who, as opposed to their
      wanting to know whether they are likely to have AD, want to deny this
      possibility. 

PMID- 23882440
TI  - Responses of mental health clinicians to patients with borderline personality
      disorder.
AB  - Borderline personality disorder is a complex psychiatric syndrome that is
      characterized by a number of pathological interpersonal and behavioral symptoms.
      Because of these symptoms, individuals with borderline personality disorder tend
      to have difficulties in their relationships with others, including mental health
      clinicians. Through a literature review, we examined the perceptions and
      reactions of mental health clinicians toward patients with borderline personality
      disorder. Our findings indicate that psychiatric nurses are the most studied
      group of mental health clinicians in this regard, followed by samples of mixed
      mental health clinicians, and then psychologists. Interestingly, there is no
      study of psychiatrists only. While sample sizes have been generally small and
      methodologies have varied, the overwhelming majority of these studies indicate
      negative perceptions of and emotional responses toward patients with borderline
      personality disorder. Some researchers have interpreted such findings to suggest
      that mental health clinicians are more judgmental or prejudicial toward patients
      with borderline personality disorder, in contrast to other types of mental health
      patients. However, patients with borderline personality disorder have very
      complex interpersonal behaviors that tend to illicit negative responses from
      those around them. Perhaps these data simply reflect a very human reaction to the
      complex and pathological behaviors of these patients-a conclusion that is
      relevant to clinicians practicing in either mental health or primary care
      settings. 

PMID- 23882441
TI  - Real-time bioacoustics monitoring and automated species identification.
AB  - Traditionally, animal species diversity and abundance is assessed using a variety
      of methods that are generally costly, limited in space and time, and most
      importantly, they rarely include a permanent record. Given the urgency of climate
      change and the loss of habitat, it is vital that we use new technologies to
      improve and expand global biodiversity monitoring to thousands of sites around
      the world. In this article, we describe the acoustical component of the Automated
      Remote Biodiversity Monitoring Network (ARBIMON), a novel combination of hardware
      and software for automating data acquisition, data management, and species
      identification based on audio recordings. The major components of the
      cyberinfrastructure include: a solar powered remote monitoring station that sends
      1-min recordings every 10 min to a base station, which relays the recordings in
      real-time to the project server, where the recordings are processed and uploaded
      to the project website (arbimon.net). Along with a module for viewing, listening,
      and annotating recordings, the website includes a species identification
      interface to help users create machine learning algorithms to automate species
      identification. To demonstrate the system we present data on the vocal activity
      patterns of birds, frogs, insects, and mammals from Puerto Rico and Costa Rica. 

PMID- 23882442
TI  - Theoretical modelling of wakes from retractable flapping wings in forward flight.
AB  - A free-wake method is used to simulate the wake from retractable, jointed wings.
      The method serves to complement existing experimental studies that visualise
      flying animal wakes. Simulated wakes are shown to be numerically convergent for a
      case study of the Rock Pigeon in minimum power cruising flight. The free-wake
      model is robust in simulating wakes for a range of wing geometries and dynamics
      without requiring changes to the numerical method. The method is found to be
      useful for providing low order predictions of wake geometries. However, it is not
      well suited to reconstructing 3d flowfields as solutions are sensitive to the
      numerical mesh node locations. 

PMID- 23882443
TI  - Visualization of oxygen distribution patterns caused by coral and algae.
AB  - Planar optodes were used to visualize oxygen distribution patterns associated
      with a coral reef associated green algae (Chaetomorpha sp.) and a hermatypic
      coral (Favia sp.) separately, as standalone organisms, and placed in close
      proximity mimicking coral-algal interactions. Oxygen patterns were assessed in
      light and dark conditions and under varying flow regimes. The images show
      discrete high oxygen concentration regions above the organisms during lighted
      periods and low oxygen in the dark. Size and orientation of these areas were
      dependent on flow regime. For corals and algae in close proximity the 2D optodes
      show areas of extremely low oxygen concentration at the interaction interfaces
      under both dark (18.4 +/- 7.7 umol O2 L(- 1)) and daylight (97.9 +/- 27.5 umol O2
      L(- 1)) conditions. These images present the first two-dimensional visualization
      of oxygen gradients generated by benthic reef algae and corals under varying flow
      conditions and provide a 2D depiction of previously observed hypoxic zones at
      coral algae interfaces. This approach allows for visualization of locally
      confined, distinctive alterations of oxygen concentrations facilitated by benthic
      organisms and provides compelling evidence for hypoxic conditions at coral-algae
      interaction zones. 

PMID- 23882444
TI  - Biological oxygen demand optode analysis of coral reef-associated microbial
      communities exposed to algal exudates.
AB  - Algae-derived dissolved organic matter has been hypothesized to induce mortality
      of reef building corals. One proposed killing mechanism is a zone of hypoxia
      created by rapidly growing microbes. To investigate this hypothesis, biological
      oxygen demand (BOD) optodes were used to quantify the change in oxygen
      concentrations of microbial communities following exposure to exudates generated
      by turf algae and crustose coralline algae (CCA). BOD optodes were embedded with
      microbial communities cultured from Montastraea annularis and Mussismilia
      hispida, and respiration was measured during exposure to turf and CCA exudates.
      The oxygen concentrations along the optodes were visualized with a low-cost
      Submersible Oxygen Optode Recorder (SOOpR) system. With this system we observed
      that exposure to exudates derived from turf algae stimulated higher oxygen
      drawdown by the coral-associated bacteria than CCA exudates or seawater controls.
      Furthermore, in both turf and CCA exudate treatments, all microbial communities
      (coral-, algae-associated and pelagic) contributed significantly to the observed
      oxygen drawdown. This suggests that the driving factor for elevated oxygen
      consumption rates is the source of exudates rather than the initially introduced
      microbial community. Our results demonstrate that exudates from turf algae may
      contribute to hypoxia-induced coral stress in two different coral genera as a
      result of increased biological oxygen demand of the local microbial community.
      Additionally, the SOOpR system developed here can be applied to measure the BOD
      of any culturable microbe or microbial community. 

PMID- 23882445
TI  - Influence of coral and algal exudates on microbially mediated reef metabolism.
AB  - Benthic primary producers in tropical reef ecosystems can alter biogeochemical
      cycling and microbial processes in the surrounding seawater. In order to quantify
      these influences, we measured rates of photosynthesis, respiration, and dissolved
      organic carbon (DOC) exudate release by the dominant benthic primary producers
      (calcifying and non-calcifying macroalgae, turf-algae and corals) on reefs of
      Mo'orea French Polynesia. Subsequently, we examined planktonic and benthic
      microbial community response to these dissolved exudates by measuring bacterial
      growth rates and oxygen and DOC fluxes in dark and daylight incubation
      experiments. All benthic primary producers exuded significant quantities of DOC
      (roughly 10% of their daily fixed carbon) into the surrounding water over a
      diurnal cycle. The microbial community responses were dependent upon the source
      of the exudates and whether the inoculum of microbes included planktonic or
      planktonic plus benthic communities. The planktonic and benthic microbial
      communities in the unamended control treatments exhibited opposing influences on
      DO concentration where respiration dominated in treatments comprised solely of
      plankton and autotrophy dominated in treatments with benthic plus plankon
      microbial communities. Coral exudates (and associated inorganic nutrients) caused
      a shift towards a net autotrophic microbial metabolism by increasing the net
      production of oxygen by the benthic and decreasing the net consumption of oxygen
      by the planktonic microbial community. In contrast, the addition of algal
      exudates decreased the net primary production by the benthic communities and
      increased the net consumption of oxygen by the planktonic microbial community
      thereby resulting in a shift towards net heterotrophic community metabolism. When
      scaled up to the reef habitat, exudate-induced effects on microbial respiration
      did not outweigh the high oxygen production rates of benthic algae, such that
      reef areas dominated with benthic primary producers were always estimated to be
      net autotrophic. However, estimates of microbial consumption of DOC at the reef
      scale surpassed the DOC exudation rates suggesting net consumption of DOC at the
      reef-scale. In situ mesocosm experiments using custom-made benthic chambers
      placed over different types of benthic communities exhibited identical trends to
      those found in incubation experiments. Here we provide the first comprehensive
      dataset examining direct primary producer-induced, and indirect microbially
      mediated alterations of elemental cycling in both benthic and planktonic reef
      environments over diurnal cycles. Our results highlight the variability of the
      influence of different benthic primary producers on microbial metabolism in reef
      ecosystems and the potential implications for energy transfer to higher trophic
      levels during shifts from coral to algal dominance on reefs. 

PMID- 23882446
TI  - A holistic approach to development of diets for Ballan wrasse (Labrus berggylta) 
      a new species in aquaculture.
AB  - Wild wrasses are used for delousing of farmed salmon but increasing demands have
      prompted the salmon industry to develop cultures of Ballan wrasse. One of the
      bottlenecks has been nutrition and feed intake in the juvenile phase, while
      broodstock nutrition is considered critical for production of viable offspring.
      The present study was aimed at developing functioning ongrowing and broodstock
      diets for Ballan wrasse. In juveniles the best lengthwise growth was identified
      at 65% dietary protein, 12% lipid and 16% carbohydrate. To investigate if the
      requirements for the other nutrients were covered by the diets developed for the
      species, the nutrient composition in juveniles (whole body) and broodstock
      (female gonad) were analyzed and compared to the composition in wild fish. We
      found that the levels of the lipid soluble Vitamins A, K and D were lower in
      cultured than in wild fish, however, the requirements for these nutrients in
      Ballan wrasse are not known. Other candidate nutrients for more in-depth
      investigation are the bone minerals, zinc, taurine and fatty acids. 

PMID- 23882447
TI  - Exposure and toxicity assessment of ultrafine particles from nearby traffic in
      urban air in seoul, Korea.
AB  - OBJECTIVES: We investigated the particle mass size distribution and chemical
      properties of air pollution particulate matter (PM) in the urban area and its
      capacity to induce cytotoxicity in human bronchial epithelial (BEAS-2B) cells.
      METHODS: To characterize the mass size distributions and chemical concentrations
      associated with urban PM, PM samples were collected by a 10-stage Micro-Orifice
      Uniform Deposit Impactor close to nearby traffic in an urban area from December
      2007 to December 2009. PM samples for in vitro cytotoxicity testing were
      collected by a mini-volume air sampler with PM10 and PM2.5 inlets. RESULTS: The
      PM size distributions were bi-modal, peaking at 0.18 to 0.32 and 1.8 to 3.2 um.
      The mass concentrations of the metals in fine particles (0.1 to 1.8 um) accounted
      for 45.6 to 80.4% of the mass concentrations of metals in PM10. The mass
      proportions of fine particles of the pollutants related to traffic emission, lead
      (80.4%), cadmium (69.0%), and chromium (63.8%) were higher than those of other
      metals. Iron was the dominant transition metal in the particles, accounting for
      64.3% of the PM10 mass in all the samples. We observed PM concentration-dependent
      cytotoxic effects on BEAS-2B cells. CONCLUSIONS: We found that exposure to PM2.5
      and PM10 from a nearby traffic area induced significant increases in protein
      expression of inflammatory cytokines (IL-6 and IL-8). The cell death rate and
      release of cytokines in response to the PM2.5 treatment were higher than those
      with PM10. The combined results support the hypothesis that ultrafine particles
      from vehicular sources can induce inflammatory responses related to environmental
      respiratory injury.

PMID- 23882448
TI  - Necessity for a national carcinogen list in Korea, based on international
      harmonization.
AB  - Cancer has been the leading cause of death in Korea for the last 30 years. Cancer
      patients' 5-year survival rate between 2005 and 2009 was 62.0%, representing a
      highly advanced standard of care, as much as developed countries in the EU and
      the US. The Korean government formulated its first 10-year plan for cancer
      control in 1996 and has been carrying out a second 10-year plan for cancer
      control since 2006. But despite the Korean government's efforts, the cancer
      burden in Korea continues to increase. Many separate laws have gone into effect
      concerning the management of carcinogen exposure. However, there are no
      integrated regulatory laws or management systems against carcinogen exposure in
      Korea. Dead zones remain where carcinogen exposure cannot be controlled properly
      in Korea. In this paper, we suggest the need to establish a national carcinogen
      list based on international harmonization as a prerequisite for a paradigm shift
      in cancer control policy from treatment to primary prevention. 

PMID- 23882449
TI  - Radiation quality, like art, consists in drawing the line somewhere.
AB  - The architects of phase I radiochemotherapy development programs impose a
      semblance of structured radiation "intensity" and adverse event predictability
      upon radiation-anticancer agent interactions whose natural complexity and
      improper mixing would otherwise lead to dire health consequences. It is incumbent
      upon radiation oncology investigators to pledge radiation quality and safety to
      the participants of radiochemotherapy trials. Measures of radiation quality and
      safety may be tools to scrutinize radiation-anticancer agent dose and schedule,
      as well as, radiation field design among diverse radiation delivery platforms. In
      this article, the merits and demerits of phase I radiochemotherapy quality and
      safety policies are critiqued considering the current era of rapidly evolving
      radiation technologies. 

PMID- 23882451
TI  - Research reporting.

PMID- 23882452
TI  - Effects of occlusal stabilization splints on obstructive sleep apnea: a
      randomized controlled trial.
AB  - AIMS: To assess the influence of occlusal stabilization splints on sleep-related
      respiratory variables in obstructive sleep apnea (OSA) patients. METHODS: Ten OSA
      patients (47.3 +/- 11.7 years of age) received a stabilization splint in the
      maxilla. All patients underwent three polysomnographic recordings with their
      splint in situ, and three recordings without their splint in situ, using a
      randomized crossover design. RESULTS: Repeated-measures ANOVAs did not yield
      statistically significant differences in the Apnea-Hypopnea Index (AHI) or in the
      Epworth Sleepiness Scale (ESS), neither between the three nights without the
      stabilization splint (AHI: F = 2.757, P = .090; ESS: F = 0.153, P = .860) nor
      between the nights with the splint in situ (AHI: F = 0.815, P = .458; ESS: F =
      0.231, P = .796). However, independent ANOVAs revealed that the mean AHI of the
      three nights with the stabilization splint in situ (17.4 +/- 7.0 events/hour) was
      significantly higher than that of the nights without the splint in situ (15.9 +/-
      6.4 events/hour) (F = 7.203, P = .025). The mean increase in AHI with the splint
      in situ was 1.4 +/- 1.7 (95% confidence interval = -1.9-4.7). No difference in
      ESS was found when both conditions were compared (F = 1.000, P = .343).
      CONCLUSION: The use of an occlusal stabilization splint is associated with a risk
      of aggravation of OSA; however, the effect size was small, which reduces the
      clinical relevance of the study.

PMID- 23882450
TI  - Human rhabdomyosarcoma cell lines for rhabdomyosarcoma research: utility and
      pitfalls.
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and
      adolescence. Despite intergroup clinical trials conducted in Europe and North
      America, outcomes for high risk patients with this disease have not significantly
      improved in the last several decades, and survival of metastatic or relapsed
      disease remains extremely poor. Accrual into new clinical trials is slow and
      difficult, so in vitro cell-line research and in vivo xenograft models present an
      attractive alternative for preclinical research for this cancer type. Currently,
      30 commonly used human RMS cell lines exist, with differing origins, karyotypes,
      histologies, and methods of validation. Selecting an appropriate cell line for
      RMS research has important implications for outcomes. There are also potential
      pitfalls in using certain cell lines including contamination with murine stromal
      cells, cross-contamination between cell lines, discordance between the cell line
      and its associated original tumor, imposter cell lines, and nomenclature errors
      that result in the circulation of two or more presumed unique cell lines that are
      actually from the same origin. These pitfalls can be avoided by testing for
      species-specific isoenzymes, microarray analysis, assays for subtype-specific
      fusion products, and short tandem repeat analysis. 

PMID- 23882453
TI  - Neuroplasticity in the adaptation to prosthodontic treatment.
AB  - AIMS: To investigate cerebral cortical changes by using functional magnetic
      resonance imaging (fMRI) after denture renewal and to test how these relate to
      prosthodontic treatment adaptability as measured by chewing efficiency and
      maximum bite force. METHODS: Ten complete denture wearers (five women and five
      men, mean age +/- standard deviation: 70.3 +/- 9.1 years) participated in the
      study. Each had their complete dentures renewed and underwent an fMRI examination
      with three functional tasks (lip pursing; jaw tapping; jaw clenching) as well as
      a color-mixing test for chewing efficiency and unilateral maximum bite force
      measurements. Recordings were performed with the old dentures (T0) and with the
      new dentures on insertion (T1) and at 1 week (T2) and 3 months postinsertion
      (T3). At T1, denture stability and retention (S/T) were assessed by two
      independent operators. Wilcoxon signed rank tests and Spearman's rho correlation
      were carried out for data analysis. RESULTS: The right and the left precentral
      gyrus (PRCG) and postcentral gyrus (POCG) were identified with significant
      activation across all three functional tasks. A statistically significant
      increase in the level of activity between T0 and T2 (POCG: P = .022; PRCG: P =
      .017) was found during jaw clenching tasks. Both regions of interest (PRCG, POCG)
      appeared to correlate with S/T of the new dentures while the subject performed a
      lip-pursing task (PRCG: r = 0.689, P = .027; POCG: r = 0.665, P = .036). The
      chewing efficiency and maximum bite force increased significantly during the
      adaptation to replacement dentures (chewing efficiency: T1-T2 P = .032, T2-T3 P =
      .012; maximum bite force right side: T2-T3 P = .047). CONCLUSION: Changes in
      brain activity occurred in the adaptation to replacement dentures and appeared to
      regain preinsertion activity levels during motor tasks involving the dental
      occlusion after 3 months postinsertion.

PMID- 23882454
TI  - Temporomandibular disorder pain after whiplash trauma: a systematic review.
AB  - AIMS: To assess, by systematic review of the literature, (1) the prevalence and
      incidence of temporomandibular disorder (TMD) pain after whiplash trauma, and (2)
      whether treatment modalities commonly used for TMD are equally effective in
      patients with solely TMD pain and those with TMD/whiplash-associated disorders
      (WAD) pain. METHODS: A systematic literature search of the PubMed, Cochrane
      Library, and Bandolier databases was conducted from January 1966 through October
      2012. The systematic search identified 125 articles. After an initial screening
      of abstracts, 45 articles were reviewed in full text. Two investigators evaluated
      the methodological quality of each identified study. RESULTS: Eight studies on
      prevalence/incidence of TMD pain in WAD and four studies on interventions in TMD
      pain and WAD met the inclusion criteria. The reported median prevalence of TMD
      pain after whiplash trauma was 23% (range 2.4% to 52%) and the incidence ranged
      from 4% to 34%. For healthy controls, the reported median prevalence was 3%
      (range 2.5% to 8%) and the incidence ranged from 4.7% to 7%. For patients with a
      combination of TMD pain and WAD, treatment modalities conventionally used for
      TMD, such as jaw exercises and occlusal splints, had less of an effect (median
      improvement rate of 48%, range 13% to 68%) compared to TMD patients without a
      whiplash injury (75%, range 51% to 91%). CONCLUSION: There is some evidence that
      prevalence and incidence of TMD pain is increased after whiplash trauma. The
      poorer treatment outcome suggests that TMD pain after whiplash trauma has a
      different pathophysiology compared to TMD pain localized to the facial region.

PMID- 23882455
TI  - Why seek treatment for temporomandibular disorder pain complaints? A study based
      on semi-structured interviews.
AB  - AIMS: To identify potential predictors of self-reported sleep bruxism (SB) within
      children's family and school environments. METHODS: A Aims: To assess possible
      differences between care seekers and non-care seekers with temporomandibular
      disorder (TMD) pain complaints, by using semi-structured interviews. METHODS:
      Semi-structured interviews were held with 16 subjects who had TMD- pain
      complaints: 8 care seekers and 8 non-care seekers, matched for age, sex, pain
      intensity, and fear of movement. Subjects were selected from a previously held
      survey study, with their consent. The interviews were audiotaped, transcribed
      verbatim, and analyzed according to qualitative content analysis. RESULTS: From
      the analysis, seven themes differentiating care seekers from non-care seekers
      were identified: catastrophizing, pain management, assertiveness, critical
      attitude towards health care, confidence in medical care, recognition, and
      adequate referral. CONCLUSION: Aspects upon which care seekers differed from non
      care seekers were mainly person-related characteristics. Next to these
      characteristics, it appeared that inadequate referrals may play a role in care
      seeking. The use of semi-structured interviews may further improve insights into
      processes that determine care seeking among people with TMD pain complaints.

PMID- 23882456
TI  - Characteristics of pain assessed with visual analog scale and questionnaire in
      burning mouth syndrome patients: a pilot study.
AB  - AIMS: To test the validity of the use of the Douleur Neuropathique en 4 Questions
      (DN4) questionnaire for burning mouth syndrome (BMS) patients, and to
      differentiate patients by measuring the time course of the pain in BMS patients
      over a period of 7 days with a visual analog scale (VAS). METHODS: Patients
      completed the DN4 questionnaire and a VAS every hour for 7 days. The data were
      expressed as mean +/- SEM. Correlations were searched using the Spearman
      correlation test with a significance level at P < .05. RESULTS: Data were fully
      analyzed for the 22 patients (21 females, 1 male, mean [+/- SEM] age 62.7 +/- 2.3
      years) for the DN4 and 17 patients for the VAS. DN4 scores ranged from 2 to 7
      (mean score: 3.9 +/- 0.3), and 59% of the patients had a DN4 score >= 4. Burning
      was found in all the patients, followed by pricking pain (pins and needles) and
      allodynia (pain on brushing) (both 68%), tingling (45%), numbness (32%), itching
      (27%), and electrical discharges (23%). Monitoring the hourly time-course of the
      pain led to the identification of two groups with intermittent or constant pain.
      In the latter, averaging the VAS for 7 days enabled plotting a curve, the slope
      of which could be calculated. The range of the slopes was 0.00 to 0.59, and a
      regular increase of pain during the day was seen for the majority of the
      patients. CONCLUSION: The findings support the use of DN4 as a tool for screening
      BMS and reinforce the view that BMS is a clinical manifestation of a neuropathic
      disease. The methodology of this study can be used for a better description of
      the patients and the identification of subgroups.

PMID- 23882457
TI  - Effect of propranolol on hypertonic saline-evoked masseter muscle pain and
      autonomic response in healthy women during rest and mental arithmetic task.
AB  - AIMS: To investigate in a randomized, double-blinded, placebo controlled,
      crossover study the effect of a single dose of the nonselective beta-adrenergic
      receptor antagonist propranolol (40 mg) on hypertonic saline (HS)-evoked masseter
      muscle pain and autonomic activity during rest and during a mental arithmetic
      task (Paced Auditory Serial Addition Task, PASAT). METHODS: Sixteen healthy women
      participated in two sessions in which propranolol or placebo was administered
      orally prior to two 5-minute infusions (30 minutes apart) of HS in the masseter
      muscle. The second HS infusion was combined with PASAT. HS-evoked pain intensity
      was scored on a numeric rating scale (NRS, 0 to 10). Heart rate variability and
      hemodynamic measures were recorded noninvasively (Task Force Monitor). Data were
      analyzed with repeated measurements analysis of variance (ANOVA). RESULTS:
      Propranolol did not reduce NRS pain scores compared with placebo but did induce
      significant autonomic changes with reduced heart rate and increased heart rate
      variability (standard deviations of all normal RR intervals; root mean square
      successive differences; low-frequency power; high-frequency power; and total
      power) independent of the mental task. CONCLUSION: A single dose of propranolol
      had no effect on acute HS-evoked pain levels during rest or during mental
      arousal. However, it influenced the tone of the autonomic nervous system,
      possibly reflecting an anxiolytic effect.

PMID- 23882458
TI  - Effects of intra-alveolar placement of 0.2% chlorhexidine bioadhesive gel on dry
      socket incidence and postsurgical pain: a double-blind split-mouth randomized
      controlled clinical trial.
AB  - AIMS: To assess the effects of intra-alveolar application of chlorhexidine gel on
      the incidence of alveolar osteitis (dry socket) and the severity of postsurgical
      pain. METHODS: A total of 160 impacted mandibular third molars were extracted in
      80 patients enrolled in this trial. In each subject, a socket was randomly
      selected and packed to the crest of the alveolar ridge with a gelatin sponge
      dressing saturated in 0.2% chlorhexidine gel. The contralateral socket was packed
      with a dry dressing as the placebo. None of the included patients took
      antibiotics or analgesics. The occurrence of dry socket and patients' pain levels
      were assessed at the first and third postoperative days. The data were analyzed
      using Spearman correlation coefficient, McNemar, Wilcoxon, and chi-square tests.
      RESULTS: Chlorhexidine gel significantly reduced dry socket incidence from 32.6%
      to 11.3% (P <= .001 [McNemar and chi-square], absolute risk reduction = 21.2%,
      relative risk reduction = 65.4%, odds ratio = 0.263, relative risk = 0.345). It
      also significantly relieved postoperative pain on both sides in all the patients
      (P <= .001 [Wilcoxon]) and also in the 54 subjects who did not develop dry socket
      (P <= .001 [Wilcoxon]). CONCLUSIONS: Besides decreasing the incidence of dry
      socket, chlorhexidine gel can reduce postsurgical pain in patients with and
      without dry socket.

PMID- 23882459
TI  - Influence of test site and baseline temperature on orofacial thermal thresholds.
AB  - AIMS: To investigate thermal thresholds of selected orofacial sites, determine if
      there is a relationship between thermal thresholds at each site, and analyze the
      influence of two different baseline temperatures on thermal thresholds at the
      tongue tip. METHODS: Thirty healthy men (mean age, 26 years) participated. Cold
      detection (CDT), warm detection (WDT), cold pain (CPT), and heat pain (HPT)
      thresholds were measured bilaterally at five orofacial sites (mentum, lower lip,
      cheek, forehead, and tongue tip). Relations between thermal thresholds at each
      test site were assessed. Thermal sensitivity of the tongue tip was compared at
      two different baseline temperatures (32 degrees C and 36 degrees C). One-way
      ANOVA, Turkey post-hoc test, paired t test and Pearson's correlation were used
      for statistical analyses. RESULTS: There was a significant difference for CDT,
      WDT, and HPT between test sites (ANOVA, P < .001) but no significant difference
      for CPT (P = .634). Subjects sensitive to cooling were sensitive to warming at
      the mentum (r = 0.379), tongue tip (r = 0.610), and cheek (r = 0.431) but not at
      the other test sites. There was a strong negative correlation between CPT and HPT
      at all test sites. There was no significant difference for CDT and WDT at the
      baseline temperature of 36 degrees C (paired t test, P = .660), but there was a
      significant difference at the baseline temperature of 32 degrees C (P < .001).
      There were no significant differences between CPTs at the two different baseline
      temperatures (P = .773), while a significant difference existed between HPTs (P =
      .034). CONCLUSION: Thermal thresholds varied between the orofacial test sites,
      and baseline temperature affected thermal sensitivity of the tongue. Subjects who
      were relatively sensitive to cold tended to be more sensitive to heat.

PMID- 23882460
TI  - Cross-cultural adaptation and validation for Portuguese (Brazilian) of the
      pictorial representation of illness and self measure instrument in orofacial pain
      patients.
AB  - AIMS: To translate the Pictorial Representation of Illness and Self Measure
      (PRISM) instrument from German to Portuguese (Brazilian) and adapt it to the
      Brazilian cultural context, and then assess its reliability and validity in
      orofacial pain patients. METHODS: The PRISM was translated to Portuguese then
      back-translated to German. The translated PRISM was evaluated by a
      multidisciplinary committee and administered as a pre-test to 30 Portuguese
      speaking orofacial pain patients. Psychometric properties were obtained after
      testing 116 orofacial pain patients. Validity was obtained through correlation
      analyses of scores obtained from PRISM and other psychometric tests, including
      the Numerical Pain Scale (NPS), Insomnia Severity Index (ISI), and Hospital
      Anxiety and Depression Scale (HAD). RESULTS: The adapted instrument showed high
      levels of reliability, proven by means of the test-retest procedure, and
      calculation of the Intraclass Correlation Coefficient (ICC = 0.991). Significant
      correlations were found between PRISM and the other tests. Correlation with NPS
      was moderate (-0.42), whereas correlations with ISI (-0.24), HAD-anxiety (-0.25),
      and HAD-depression (-0.22) were weak. CONCLUSION: The cross-cultural adaptation
      process of PRISM was successful and the adapted version offers reliable and valid
      psychometric properties in the Brazilian context.

PMID- 23882461
TI  - Effect of surface treatments on the bonding strength of self-adhesive resin
      cements to zirconia ceramics.
AB  - OBJECTIVE: To investigate the effect of surface treatments on the surface
      properties of yttria-stabilized zirconia ceramics (Y-TZP) and the interfacial
      bond strength to self-adhesive resin cements. METHOD AND MATERIALS: Two types of
      Y-TZP (Vita In-Ceram YZ [VZ] and IPS e.max ZirCAD [IZ]) were used. The specimens
      were divided into four groups in each test according to the surface treatment
      used: Group A (control; no treatment), Group B (airborne-particle abrasion),
      Group C (CH2Cl2 for 60 minutes), and Group D (hot etching for 60 minutes).
      Scanning electron microscopy, atomic force microscopy, and X-ray diffractometry
      were carried out. Two types of self-adhesive resin cements (i CEM [IC] and
      Multilink Speed [MS]) were used for testing the adhesion. The G-value (J/m2) was
      measured with a four-point bending configuration. Following fracture testing,
      specimens were examined with a stereomicroscope. Data were analyzed using ANOVA
      and Tukey test. RESULTS: IZ treated with hot etching showed the highest average
      surface roughness values (172.5 +/- 15.43 nm) compared with the other groups (P <
      .05). The greatest amount of monoclinic phase was measured after airborne
      particle abrasion for VZ (8.9%), followed by IZ (6.1%). Improvements in bond
      strength values were found in the following order: hot etching > CH2Cl2 >
      airborne-particle abrasion > no treatment. Most failure modes were adhesive type
      of failures between ceramics and cement material (68.76%). CONCLUSION: Adhesion
      between Y-TZP and self-adhesive resin cements can be improved by the use of
      CH2Cl2 or hot etching surface treatments prior to resin cement application as an
      alternative technique to airborne-particle abrasion treatment.

PMID- 23882462
TI  - Dual signal amplification of zinc oxide nanoparticles and quantum dots
      functionalized zinc oxide nanoparticles for highly sensitive
      electrochemiluminescence immunosensing.
AB  - A novel electrochemiluminescence (ECL) immunosensor for highly sensitive
      detection of alpha-fetoprotein (AFP) based on a dual signal amplification
      strategy was developed. Zinc oxide (ZnO) nanoparticles were employed as the
      carriers for immobilizing the capture AFP antibody (Ab1) and CdSe quantum dots
      (QDs). CdSe QDs-functionalized ZnO nanoparticles were used as the tracer to label
      the signal AFP antibody (Ab2). CdSe QDs-functionalized ZnO nanoparticles were
      prepared through an amide dehydration reaction and they were characterized by
      transmission electron microscopy and Fourier transform infrared spectroscopy. The
      Ab2 was bound to the CdSe QDs-functionalized ZnO nanoparticles to obtain the
      detection probe. ZnO nanoparticles could accelerate electron transfer between the
      detection probe and the electrode, and their large surface area was beneficial
      for loading more CdSe QDs, leading to an enhanced ECL signal (0.9-fold increase)
      by a sandwich immunoreaction. This also indicated efficient association of the
      detection probe on the immunosensor surface. The designed immunoassay showed a
      wide linear range from 0.5 to 600 ng mL(-1) with a detection limit of 0.48 ng mL(
      1) at a S/N ratio of 3 for AFP detection. The ECL immunosensor exhibited good
      analytical performance and was successfully applied to clinical sample detection,
      showing a promising application in ECL biosensing. 

PMID- 23882463
TI  - An X-ray transparent microfluidic platform for screening of the phase behavior of
      lipidic mesophases.
AB  - Lipidic mesophases are a class of highly ordered soft materials that form when
      certain lipids are mixed with water. Understanding the relationship between the
      composition and the microstructure of mesophases is necessary for fundamental
      studies of self-assembly in amphiphilic systems and for applications, such as the
      crystallization of membrane proteins. However, the laborious formulation protocol
      for highly viscous mesophases and the large amounts of material required for
      sample formulation are significant obstacles in such studies. Here we report a
      microfluidic platform that facilitates investigations of the phase behavior of
      mesophases by reducing sample consumption 300-fold, and automating and
      parallelizing sample formulation. The mesophases were formulated on-chip using
      less than 80 nL of material per sample and their microstructure was analyzed in
      situ using small-angle X-ray scattering (SAXS). The 220 MUm-thick X-ray
      compatible platform was comprised of thin polydimethylsiloxane (PDMS) layers
      sandwiched between cyclic olefin copolymer (COC) sheets. Uniform mesophases were
      prepared using an active on-chip mixing strategy coupled with periodic cooling of
      the sample to reduce viscosity. We validated the platform by preparing and
      analyzing mesophases of the lipid monoolein (MO) mixed with aqueous solutions of
      different concentrations of beta-octylglucoside (betaOG), a detergent frequently
      used in membrane protein crystallization. Four samples were prepared in parallel
      on chip, by first metering and automatically diluting betaOG to obtain detergent
      solutions of different concentration, then metering MO, and finally mixing by
      actuation of pneumatic valves. Integration of detergent dilution and subsequent
      mixing significantly reduced the number of manual steps needed for sample
      preparation. Three different types of mesophases typical for MO were successfully
      identified in SAXS data from on-chip samples. Microstructural parameters of
      identical samples formulated in different chips showed excellent agreement. Phase
      behavior of samples on-chip (~80 nL per sample) corresponded well with that of
      samples prepared via the traditional coupled-syringe method using at least two
      orders of magnitude more material ("off-chip", 35-40 MUL per sample), further
      validating the applicability of the microfluidic platform for on-chip
      characterization of mesophase microstructure. 

PMID- 23882464
TI  - Fast transport of HCl across a hydrophobic layer over macroscopic distances by
      using a Pt(II) compound as the transporter.
AB  - [Pt(H-(ethyl)2-dithiooxamidate)2] plays the role of a HCl symporter, allowing
      fast HCl transport over macroscopic distances (cm scale) across a hydrophobic
      layer made of a chloroform solution, without any stirring. The process is limited
      by interfacial transfer, whereas HCl is transported within the hydrophobic phase
      at extremely high rates. 

PMID- 23882465
TI  - Solid phase synthesis of glycopeptides using Shoda's activation of unprotected
      carbohydrates.
AB  - An expedient and simple protocol to access S-linked glycopeptides by Fmoc SPPS
      using unprotected carbohydrates is reported. The utility of the method was
      demonstrated with the solid phase synthesis of a MUC1 fragment (20 mer)
      containing two glycosylation sites that were substituted with S-linked glycans. 

PMID- 23882466
TI  - A 'two-point' bound zinc porphyrin-zinc phthalocyanine-fullerene supramolecular
      triad for sequential energy and electron transfer.
AB  - A novel supramolecular triad composed of a zinc porphyrin-zinc phthalocyanine
      dyad and fullerenes has been assembled using a 'two-point' axial binding
      approach, and occurrence of efficient photoinduced energy transfer followed by
      electron transfer is demonstrated. 

PMID- 23882467
TI  - Nickel-catalyzed manipulation of tertiary phosphines via highly selective C-P
      bond cleavage.
AB  - A catalytic cycle involving oxidative addition of nickel(0) with a carbon-carbon
      single bond in the three-membered ring of
      diarylmethylenecyclopropa[b]naphthalenes, highly selective cleavage of the C-P
      bond, and migration of the aryl group of phosphine consequently provides a new
      type of bulky phosphine in excellent yields. 

PMID- 23882686
TI  - Entrance pupil size predicts retinal illumination in darkly pigmented eyes, but
      not lightly pigmented eyes.
AB  - PURPOSE: We determined the effect of entrance pupil size on retinal illumination.
      The influence of unilateral miosis on the magnitude of the pupil light reflex was
      studied to ascertain how a clinically significant anisocoria influences the
      relative afferent pupil defect (RAPD). METHODS: Miosis was induced by topical 1%
      pilocarpine in the right eye of 14 healthy subjects with normal eyes. The
      interocular difference in retinal illumination was assessed by computerized
      pupillometry from the stimulus response curve of the right and left eyes. The
      main outcome measure was the RAPD, determined by computerized pupillography, at
      baseline and after pilocarpine-induced anisocoria. RESULTS: Induced anisocoria
      produced a significant change in RAPD from baseline (mean = 1.60 dB in the miotic
      eye, P = 0.007). However, anisocoria correlated with RAPD only in subjects with
      darkly pigmented irides (Pearson correlation coefficient 0.793, P = 0.05).
      CONCLUSIONS: In darkly pigmented eyes, entrance pupil size significantly
      influenced the retinal illumination. However, retinal illumination of lightly
      pigmented eyes is relatively independent of entrance pupil size, presumably due
      to extrapupillary transmission of light through the iris and sclera. This has
      important implications in understanding the potential influence of anisocoria on
      the RAPD and also greater susceptibility of lightly pigmented eyes to light
      toxicity.

PMID- 23882687
TI  - Polychromatic angiography for the assessment of VEGF-induced BRB dysfunction in
      the rabbit retina.
AB  - PURPOSE: To determine the utility of polychromatic angiography (PCA) in the
      assessment of VEGF-induced blood retinal barrier (BRB) dysfunction in rabbits.
      METHODS: Twenty-six eyes of 24 Dutch Belted rabbits were injected intravitreally
      with 1.25 MUg (group A, n = 5), 10 MUg (group C, n = 7), or 4 MUg (group B, n =
      6; group D, n = 4; and group E, n = 4) of VEGF on day 0. Groups D and E were also
      injected intravitreally with 1.25 MUg and 12.5 MUg bevacizumab, respectively, on
      day 2. On days 0, 2, 4, 7, 11, and 14, PCA was performed using a contrast agent
      mixture composed of fluorescein sodium, indocyanine green, PCM102, and PCM107 and
      imaged with a modified fundus camera. PCA scores were based on detected leaking
      fluorophores. RESULTS: On day 7, there was a statistically significant difference
      between PCA scores of group A (0.6 +/- 0.89) and both groups B (2.67 +/- 1.37, P
      = 0.0154) and C (3.33 +/- 0.52, P = 0.00085). There was also a statistically
      significant difference between groups B and E (PCA score 0.75 +/- 0.96, P =
      0.032) on day 7. On day 11, there was statistically significant difference
      between group C (1.80 +/- 1.1) and both groups A (0, P = 0.021) and B (0.33 +/-
      0.52, P = 0.037). CONCLUSIONS: A differential response to both increasing VEGF
      dose and administration of bevacizumab could be discerned using the PCA. PCA
      allowed stratification of VEGF-induced BRB dysfunction and inhibitory effects of
      bevacizumab therapy in the rabbit retina.

PMID- 23882688
TI  - Evaluation of contact lens-induced changes in keratoconic corneas using in vivo
      confocal microscopy.
AB  - PURPOSE: To quantitatively analyze laser scanning in vivo confocal microscopy
      (IVCM) images of all corneal layers in contact lens-wearing and noncontact lens
      wearing keratoconus patients. METHODS: The study population included rigid gas
      permeable (RGP) contact lens-wearing keratoconus patients (group 1; N = 29),
      keratoconus patients who did not wear contact lenses (group 2; N = 30), and
      subjects who neither had keratoconus nor wore contact lenses (group 3; N = 30),
      with groups 2 and 3 matched to group 1 by age and sex. The central cornea was
      examined with IVCM in all subjects. The mean duration of contact lens wear was
      5.50 +/- 3.68 years (range, 2-15 years). RESULTS: Eyes with keratoconus showed
      significantly lower basal epithelial cell and anterior and posterior stromal
      keratocyte densities, as well as subbasal nerve fiber density, nerve branch
      density, and nerve fiber length compared with healthy control subjects.
      Furthermore, compared with group 2, group 1 had significantly lower basal
      epithelial cell density (4920 +/- 476 cells/mm(2) vs. 4503 +/- 461 cells/mm(2), P
      = 0.001) and anterior stromal keratocyte density (561 +/- 91 cells/mm(2) vs. 464
      +/- 55 cells/mm(2), P < 0.001), but there was no significant difference for
      posterior stromal keratocyte density (P = 0.808), endothelial cell density (P =
      0.699), or subbasal nerve fiber density (P = 0.142), nerve branch density (P =
      0.614), and nerve fiber length (P = 0.850). CONCLUSIONS: Significant corneal
      microstructural abnormalities were observed in eyes with keratoconus. RGP contact
      lens wear was associated with a further reduction in the basal epithelial cell
      and anterior stromal keratocyte densities, but with no effect on posterior
      stromal keratocyte density, endothelial cell density, or corneal nerve
      morphology.

PMID- 23882689
TI  - The influence of intersubject variability in ocular anatomical variables on the
      mapping of retinal locations to the retinal nerve fiber layer and optic nerve
      head.
AB  - PURPOSE: To investigate the influence of intersubject variation in ocular
      parameters on the mapping of retinal locations to the retinal nerve fiber layer
      and optic nerve head. METHODS: One hundred retinal nerve fiber layer (RNFL)
      bundle photographs from 100 subjects were optimized digitally and single RNFL
      bundles manually traced back to the ONH where their entry point was noted. A 24-2
      visual field (VF) grid pattern was superimposed onto the photographs in order to
      relate VF test points to intersecting RNFL bundles and their entry angles into
      the ONH. Axial length, spherical equivalent, the position of the ONH in relation
      to the fovea, size, orientation, tilt, and shape of the ONH were assessed.
      Multilevel linear models were generated for predicting the entry angle of RNFL
      bundles, based on ocular parameters. RESULTS: A total of 6388 RNFL bundles were
      traced. The influence of ocular parameters could be evaluated for 33 out of 52 VF
      locations. The position of the ONH in relation to the fovea was the most
      prominent predictor for variations in the mapping of retinal locations to the
      ONH, followed by disc area, axial length, spherical equivalent, disc shape, disc
      orientation, and disc tilt. CONCLUSIONS: Mapping of retinal locations to the
      optic nerve head varies between patients according to a given patient's ocular
      parameters. By considering these parameters, patient-tailored, structure-function
      maps can be built and structural and functional measurements can be correlated
      more accurately. Individualized maps may assist clinicians detecting glaucoma and
      monitoring glaucomatous progression.

PMID- 23882690
TI  - Role of PKCalpha activation of Src, PI-3K/AKT, and ERK in EGF-stimulated
      proliferation of rat and human conjunctival goblet cells.
AB  - PURPOSE: To determine the order and components of the signaling pathway utilized
      by epidermal growth factor (EGF) to stimulate conjunctival goblet cell
      proliferation. METHODS: Goblet cells from rat bulbar and forniceal conjunctiva
      and human bulbar conjunctiva were grown in organ culture. Goblet cells (GCs) were
      serum starved for 24 hours and preincubated with inhibitors for 30 minutes or
      small interfering RNA (siRNA) for 48 hours prior to addition of EGF.
      Proliferation was then measured or Western blot analysis was performed using
      antibodies against phosphorylated protein kinase B (AKT), extracellular signal
      regulated kinase 1/2 (ERK1/2), or the non-receptor tyrosine kinase Src. Rat GCs
      were also incubated with adenoviruses expressing dominant negative protein kinase
      Calpha (DNPKCalpha) or constitutively activated protein kinase Calpha
      (myrPKCalpha), and activation of AKT and ERK1/2 was determined by Western blot
      analysis. RESULTS: Inhibitors of phosphoinositol-3 kinase (PI-3K)/AKT pathway
      blocked EGF-stimulated ERK1/2 activation and GC proliferation. Inhibitors of EGF
      stimulated ERK1/2 activity did not inhibit AKT activation but blocked
      proliferation. DNPKCalpha blocked EGF-stimulated activation of AKT and ERK1/2
      while myrPKCalpha increased activation of these kinases. Inhibitors of PI-3K,
      ERK1/2, and protein kinase C (PKC) blocked myrPKCalpha-stimulated GC
      proliferation. EGF and myrPKCalpha increased phosphorylation of Src, and
      inhibition of Src with the chemical inhibitor PP1 or siRNA inhibited EGF
      stimulated GC proliferation. CONCLUSIONS: We found that EGF activates a major
      pathway to stimulate goblet cell proliferation. This pathway consists of
      induction of phospholipase C (PLC)gamma to activate PKCalpha. Active PKCalpha
      phosphorylates Src to induce PI-3K to phosphorylate AKT that subsequently
      activates the ERK1/2 cascade to stimulate goblet cell proliferation.

PMID- 23882691
TI  - The effects of tenascin C knockdown on trabecular meshwork outflow resistance.
AB  - PURPOSE: Tenascin C (TNC) is a matricellular glycoprotein whose expression in
      adult tissue is indicative of tissue remodeling. The purpose of the current study
      was to determine the localization of TNC in trabecular meshwork (TM) tissue and
      to analyze the effects of TNC on intraocular pressure (IOP). METHODS: Human TM
      frontal sections were immunostained with anti-TNC and imaged by confocal
      microscopy. TNC mRNA and protein levels were quantitated in anterior segments
      perfused at physiological and elevated pressure. Short, hairpin RNA (shRNA)
      silencing lentivirus targeting full-length TNC (shTNC) was applied to anterior
      segment perfusion organ cultures. The IOPs and central corneal thickness (CCT) of
      wild-type, TNC(-/-), and tenascin X (TNX(-/-)) knockout mice were measured.
      RESULTS: TNC was distributed in the juxtacanalicular (JCT) region of adult human
      TM, predominantly in the basement membrane underlying the inner wall of Schlemm's
      canal. Application of shTNC lentivirus to human and porcine anterior segments in
      perfusion culture did not significantly affect outflow rate. Although TNC was
      upregulated in response to pressure, there was no difference in outflow rate when
      shTNC-silenced anterior segments were subjected to elevated pressure.
      Furthermore, IOPs and CCTs were not significantly different between TNC(-/-) or
      TNX(-/-) and wild-type mice. CONCLUSIONS: TNC does not appear to contribute
      directly to outflow resistance. However, TNC immunolocalization in the JCT of
      adult human eyes suggests that certain areas of the TM are being continuously
      remodeled with or without an IOP increase.

PMID- 23882693
TI  - Perimetric evaluation of saccadic latency, saccadic accuracy, and visual
      threshold for peripheral visual stimuli in young compared with older adults.
AB  - PURPOSE: Using a novel automated perimetry technique, we tested the hypothesis
      that older adults will have increased latency and decreased accuracy of saccades,
      as well as higher visual thresholds, to peripheral visual stimuli when compared
      with younger adults. METHODS: We tested 20 healthy subjects aged 18 to 30 years
      ("young") and 21 healthy subjects at least 60 years old ("older") for detection
      of briefly flashed peripheral stimuli of differing sizes in eight locations along
      the horizontal meridian (+/-4 degrees , +/-12 degrees , +/-20 degrees , and +/-28
      degrees ). With the left eye occluded, subjects were instructed to look quickly
      toward any seen stimuli. Right eye movements were recorded with an EyeLink 1000
      infrared camera system. Limiting our analysis to the four stimulus positions in
      the nasal hemifield (-4 degrees , -12 degrees , -20 degrees , and -28 degrees ),
      we evaluated for group-level differences in saccadic latency, accuracy, and
      visual threshold at each stimulus location. RESULTS: Saccadic latency increased
      as stimulus size decreased in both groups. Older subjects had significantly
      increased saccadic latencies (at all locations; P < 0.05), decreased accuracies
      (at all locations; P < 0.05), and higher visual thresholds (at the -12 degrees , 
      20 degrees , and -28 degrees  locations; P < 0.05). Additionally, there were
      significant relationships between visual threshold and latency, visual threshold
      and accuracy, and latency and accuracy (P < 0.0001). CONCLUSIONS: Older adults
      have increased latency and decreased accuracy of saccades, as well as higher
      visual thresholds, to peripheral visual stimuli when compared with younger
      adults. Saccadic latency and accuracy are related to visual threshold, suggesting
      that saccadic latency and accuracy could be useful as perimetric outcome
      measures.

PMID- 23882694
TI  - Anti-retinal antibodies in patients with macular telangiectasia type 2.
AB  - PURPOSE: Macular telangiectasia type 2 (MacTel-2) is a retinal disease that can
      cause loss of central vision. To gain better understanding of the etiology and
      pathogenesis of MacTel-2, we investigated antigens that prompt the generation of
      retinal autoantibodies in the serum of patients with MacTel-2. METHODS: We
      screened for the presence of retinal autoantibodies in 45 serum samples collected
      from patients with MacTel-2 and 58 serum samples from healthy control subjects by
      Western blot. We then isolated and identified three retinal proteins that are
      putative targets of three of the most frequently detected autoantibodies in the
      serum of patients with MacTel-2 using chromatographic fractionation and liquid
      chromatography coupled to tandem mass spectrometry. We also validated the retinal
      location of the three antigens by immunohistochemisty using MacTel-2 sera as
      primary antibodies and commercial antibodies. RESULTS: Retinal autoantibodies
      were detected in a significantly higher proportion of patients with MacTel-2 than
      in controls (31 of 45 [69%] vs. 9 of 58 [16%], P < 0.0001). The three antigens
      that were targeted by the most frequently detected MacTel-2 autoantibodies were
      identified as glycogen debranching enzyme (hereafter AGL, named for the gene
      symbol AGL), retinol-binding protein 3 (RBP3), and creatine kinase type B (CK-B);
      autoantibodies against these antigens were found in four, eleven, and nine MacTel
      2 serum samples, respectively. CONCLUSIONS: We found that most patients with
      MacTel-2 possess retinal autoantibodies, the most prevalent of which were
      directed against AGL, RBP3, and CK-B. The localization of retinal proteins bound
      by AGL, RBP3, and CK-B autoantibodies is consistent with their putative
      physiological functions. These findings provide potentially novel mechanisms for
      the etiology and pathogenesis of MacTel-2.

PMID- 23882695
TI  - Compliance with occlusion therapy for childhood amblyopia.
AB  - PURPOSE: Explore compliance with occlusion treatment of amblyopia in the
      Monitored and Randomized Occlusion Treatment of Amblyopia Studies (MOTAS and
      ROTAS), using objective monitoring. METHODS: Both studies had a three-phase
      protocol: initial assessment, refractive adaptation, and occlusion. In the
      occlusion phase, participants were instructed to dose for 6 hours/day (MOTAS) or
      randomized to 6 or 12 hour/day (ROTAS). Dose was monitored continuously using an
      occlusion dose monitor (ODM). RESULTS: One hundred and fifty-two patients (71
      male, 81 female; 122 Caucasian, 30 non-Caucasian) of mean +/- SD age 68 +/- 18
      months participated. Amblyopia was defined as an interocular acuity difference of
      at least 0.1 logMAR and was associated with anisometropia in 50, strabismus in
      44, and both (mixed) in 58. Median duration of occlusion was 99 days
      (interquartile range 72 days). Mean compliance was 44%, mean proportion of days
      with no patch worn was 42%. Compliance was lower (39%) on weekends compared with
      weekdays (46%, P = 0.04), as was the likelihood of dosing at all (52% vs. 60%, P
      = 0.028). Compliance was lower when attendance was less frequent (P < 0.001) and
      with prolonged treatment duration (P < 0.001). Age, sex, amblyopia type, and
      severity were not associated with compliance. Mixture modeling suggested three
      subpopulations of patch day doses: less than 30 minutes; doses that achieve 30%
      to 80% compliance; and doses that achieve around 100% compliance. CONCLUSIONS:
      This study shows that compliance with patching treatment averages less than 50%
      and is influenced by several factors. A greater understanding of these influences
      should improve treatment outcome. (ClinicalTrials.gov number, NCT00274664).

PMID- 23882692
TI  - Association of smoking and other risk factors with Fuchs' endothelial corneal
      dystrophy severity and corneal thickness.
AB  - PURPOSE: We investigated effects of smoking and other risk factors on the
      development of advanced Fuchs' endothelial corneal dystrophy (FECD) and on
      central corneal thickness (CCT). METHODS: Eyes from Caucasian probands, affected
      and unaffected family members, and unrelated controls matched for age from the
      FECD Genetics Multi-Center Study (n = 2044 subjects) were examined. Univariate
      and multivariate models, adjusted for family correlations, were used to determine
      the effect of smoking, sex, diabetes, and age on FECD case/control status and
      CCT. RESULTS: In a multivariate model, sex and smoking were associated
      significantly with advanced FECD (grades 4-6) development (P = 0.016 and P =
      0.047, respectively). Female sex increased odds by 34%. Smoking increased odds by
      30%. In a multivariate model, diabetes was associated with an increase of 9.1 MUm
      in average CCT (P = 0.021). Female sex was associated significantly with a
      decrease in average CCT by 6.9 MUm (P = 0.015). Smoking had no significant effect
      on CCT in any model. As shown previously, advanced FECD was associated with large
      increases in CCT (31.4-94.2 MUm). CONCLUSIONS: Smoking was associated with an
      increased risk of advanced FECD and self-reported diabetes was associated with
      increased CCT. Further study of the impact of smoking and diabetes on FECD
      development and changes in corneal thickness is warranted.

PMID- 23882696
TI  - Characterization of stargardt disease using polarization-sensitive optical
      coherence tomography and fundus autofluorescence imaging.
AB  - PURPOSE: To identify disease-specific changes in Stargardt disease (STGD) based
      on imaging with polarization-sensitive spectral-domain optical coherence
      tomography (PS-OCT) and to compare structural changes with those visible on blue
      light fundus autofluorescence (FAF) imaging. METHODS: Twenty-eight eyes of 14
      patients diagnosed with STGD were imaged using a novel high-speed, large-field PS
      OCT system and FAF (excitation 488 nm, emission > 500 nm). The ophthalmoscopic
      phenotype was classified into three groups. ABCA4 mutation testing detected 15
      STGD alleles, six of which harbor novel mutations. RESULTS: STGD phenotype 1 (12
      eyes) showed sharply delineated areas of absent RPE signal on RPE segmentation B
      scans of PS-OCT correlating with areas of hypofluorescence on FAF. Adjacent areas
      of irregular fluorescence correlated with an irregular RPE segmentation line with
      absence of overlaying photoreceptor layers. Eyes characterized on OCT by a gap in
      the subfoveal outer segment layer (foveal cavitation) showed a normal RPE
      segmentation line on PS-OCT. Hyperfluorescent flecks on FAF in phenotype 2 STGD
      (8 eyes) were identified as clusters of depolarizing material at the level of the
      RPE. Distribution of flecks could be depicted on RPE elevation maps. An increased
      amount of depolarizing material in the choroid was characteristic for STGD
      Phenotype 3 (8 eyes). CONCLUSIONS: PS-OCT together with FAF identified
      characteristic patterns of changes in different stages of the disease. PS-OCT is
      a promising new tool for diagnosis and evaluation of future treatment modalities
      in STGD.

PMID- 23882697
TI  - Novel molecular diagnostic system of limbal stem cell deficiency based on MUC5AC
      transcript detection in corneal epithelium by PCR-reverse dot blot.
AB  - PURPOSE: To evaluate the sensitivity and specificity of a PCR-strip system based
      on reverse dot blot for detection of MUC5AC mRNA in corneal epithelium samples
      from patients with limbal stem cell deficiency (LSCD), and to determine the
      correlation with clinical diagnosis. METHODS: We obtained 87 corneal impression
      cytology (IC) samples from 55 subjects (37 patients clinically diagnosed with
      LSCD and 18 control subjects). Total RNA was extracted from each IC sample and
      retrotranscribed to cDNA. MUC5AC mRNA transcript was amplified by a customized RT
      PCR assay and detected in PCR strips based on reverse dot blot hybridization and
      in agarose gels. Conjunctival IC samples were used as positive controls. RESULTS:
      Forty-four of 45 corneal IC samples obtained from patients clinically diagnosed
      with LSCD were positive for MUC5AC, whereas 34 of 42 corneal ICs from healthy
      subjects were negative for MUC5AC. Four healthy corneas were found MUC5AC
      positive, and four rendered inconclusive results. A correlation of 91.4% (P <
      0.001) between molecular testing and clinical diagnosis was found. The overall
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) of the PCR-strip system were 98%, 89%, 92%, and 97%, respectively.
      CONCLUSIONS: Corneal epithelium MUC5AC transcript detection by reverse dot blot
      PCR-strip is a highly sensitive technique for LSCD diagnosis. The test results
      strongly correlate with clinical diagnosis of characterized LSCD cases. The PCR
      strip system may be used for early detection, and for the detection of mild cases
      of LSCD, and constitutes an objective clinical tool for the monitoring of
      treatments and surgical decisions.

PMID- 23882698
TI  - Response to letter regarding article, "Childhood air pollutant exposure and
      carotid artery intima-media thickness in young adults".

PMID- 23882699
TI  - Abstracts of the SNIS (Society of NeuroInterventional Surgery) 10th Annual
      Meeting. July 29-August 1, 2013. Miami, Florida, USA.

PMID- 23882700
TI  - Commentaire de travail de Camus M et al., pp. 451.

PMID- 23882701
TI  - Commentaire de travail de G. Longcroft-Wheaton et al., pp. 426.

PMID- 23882702
TI  - Commentaire de travail de Brangewitz M et al., pp. 433.

PMID- 23882703
TI  - Commentaire de travail de Goetz M et al., pp. 469.

PMID- 23882704
TI  - Commentaire de travail de Zhu YQ et al., pp. 458.

PMID- 23882705
TI  - Commentaire de travail de Bang JY et al., pp. 445.

PMID- 23882706
TI  - Authors' reply.

PMID- 23882707
TI  - Author's reply: To PMID 23520221.

PMID- 23882709
TI  - Reply to Smith and Griffin: Methods, air flows, and conclusions are robust in the
      DeLeon-Rodriguez et al. study.

PMID- 23882708
TI  - Clinical and technical factors associated with skin intrinsic fluorescence in
      subjects with type 1 diabetes from the Diabetes Control and Complications
      Trial/Epidemiology of Diabetes Interventions and Complications Study.
AB  - BACKGROUND: The Diabetes Control and Complications Trial (DCCT)/Epidemiology of
      Diabetes Interventions and Complications(EDIC) studies have established multiyear
      mean hemoglobin A1c (HbA1c) as predictive of microvascular complications in
      persons with type 1 diabetes. However, multiyear mean HbA1c is not always
      available in the clinical setting. Skin advanced glycation end products (AGEs)
      are thought to partially reflect effects of hyperglycemia over time, and
      measurement of skin AGEs might be a surrogate for multiyear mean HbA1c. As
      certain AGEs fluoresce and skin fluorescence has been demonstrated to correlate
      with the concentration of skin AGEs, noninvasive measurement by skin intrinsic
      fluorescence(SIF) facilitates the exploration of the association of mean HbA1c
      and other clinical/technical factors with SIF using the detailed phenotypic
      database available in DCCT/EDIC. SUBJECTS AND METHODS: Of the subjects, 1,185
      (53% male) had measurements of SIF during years 16/17 of EDIC with mean age and
      diabetes duration of 51.5 and 29.8 years, respectively. SIF measurements were
      obtained on the underside of the forearm near the elbow using a skin fluorescence
      spectrometer. Demographic data and health history were self-reported, and an
      annual standardized examination measured clinical status. Linear regression
      models were constructed to identify significant clinical and technical factors
      associated with SIF, and the final models only used factors that were
      significant. RESULTS: SIF ranged from 8.7 to 54.0 arbitrary units and was log
      normally distributed. Log(SIF) correlated more with mean HbA1c as the time period
      increased. In multivariate analyses log(SIF) was significantly associated with
      mean HbA1c, age,estimated glomerular filtration rate < 60mL/min/m2, smoking
      status, skin tone, and clinic latitude <37 N. CONCLUSIONS: SIF reflects age, mean
      HbA1c over time, smoking, and renal damage, which are known risk factors for
      diabetes complications.

PMID- 23882710
TI  - Reply to de la Pena: Radiocarbon dating and the paleoenvironmental record of
      Carihuela.

PMID- 23882711
TI  - Comment on: "Second-order sliding mode control with experimental application".
AB  - In this paper, some points to the stability analysis of the paper [Eker I, Second
      order sliding mode control with experimental application, ISA Trans 2010;50:394
      405] are presented. It is illustrated that the way the author in [1] proves
      stability, suffers lack of correct justification. A modification to the stability
      analysis is presented and the stability conditions are restated. Moreover, some
      other flaws in the original paper are addressed.

PMID- 23882712
TI  - Author's response.

PMID- 23882713
TI  - The future of surgical education.

PMID- 23882714
TI  - Members of the European Parliament (MEP) Heart Group.
AB  - The MEP Heart Group is a discussion forum aimed at promoting measures to reduce
      the burden of cardiovascular disease in the European Union and raise
      cardiovascular disease as a priority on the EU political agenda.

PMID- 23882715
TI  - Air pollution and myocardial infarction mortality.
AB  - Exposure to air pollution is associated with increased mortality after myocardial
      infarction

PMID- 23882716
TI  - Cardiovascular disease data to be standardized across Europe.
AB  - ESC is to create an inventory of cardiovascular disease registries and a task
      force on data standardization

PMID- 23882717
TI  - Vegetarian diet cuts risk of heart disease by one-third.
AB  - There is no increase in life expectancy for vegetarians and the jury is out on
      the protective effects of fish

PMID- 23882718
TI  - Why complex pelvic organ prolapse should be repaired vaginally.
AB  - PURPOSE OF REVIEW: Vaginal surgery is the true minimally invasive surgery in the
      treatment of pelvic organ prolapse (POP); however, the robotic industry and
      decreased resident training in vaginal surgery may result in the loss of skills
      among our graduates. There are a number of procedures that are well accepted in
      the management of prolapse, because they are minimally invasive and with few
      complications compared with the abdominal approach. In this review, we will
      discuss various vaginal techniques for complex POP. In our opinion, the most
      minimally invasive approach is vaginal surgery. RECENT FINDINGS: There are no
      recent significant findings on the vaginal approach to complex pelvic organ
      surgery and mostly case series about success of robotic procedures. There are a
      significant number of studies exploring the benefits of robotic surgery. It has
      been observed that the operating times are longer and there is a learning curve.
      Although there are advantages to robotic surgery, one must not overlook the
      significant cost associated with obtaining the robot, the maintenance and the
      cost of disposable instruments. There is limited evidence to show that robotic
      surgery did not benefit women with benign gynecological disease in terms of
      effectiveness or safety. SUMMARY: POP is a vaginal problem, which is best treated
      vaginally. There are many well designed studies that support the vaginal approach
      to primary POP.

PMID- 23882719
TI  - Why complex pelvic organ prolapse should be approached abdominally.
AB  - PURPOSE OF REVIEW: This review summarizes the recent clinical trials that address
      the abdominal approach for treatment of uterine or vaginal vault prolapse
      following hysterectomy. RECENT FINDINGS: Open abdominal sacrocolpopexy (ASC) has
      improved anatomic and sexual functioning outcomes compared with the sacrospinous
      ligament suspension but this benefit comes with higher costs. Newer studies
      suggest that minimally invasive approaches to ASC that result in 1 day of
      hospitalization can be cost-effective. Although most studies demonstrate higher
      costs when using the robot during laparoscopic surgery, the costs of initial
      purchase and maintenance become insignificant when a single robot is used at
      least twice a day (500 procedures annually). Minimally invasive sacrocolpopexy
      appears to result in less small bowel obstruction and ileus however,
      intraoperative bowel injury rates are similar. During sacrocolpopexy, placing the
      sacral suture at the promontory may put the L5-S1 intervetebral disc at risk,
      while placing the suture 5 mm below the promontory would ensure the suture is at
      the level of S1 vertebrae. Lastly, the use of cadaveric fascia lata as an
      alternative to polypropylene mesh for sacrocolpopexy in patients who were
      followed for 5 years, results in decreased anatomic outcomes, similar subjective
      outcomes and surprisingly, similar mesh erosion rates. SUMMARY: One of the
      significant benefits of sacrocolpopexy is that it is not a procedure that has
      been developed for profit. As a result, the procedure has evolved based on
      modifications suggested by surgeons with no financial gain. Minimally invasive
      approaches to ASC allow for the benefits of ASC with significant reductions in
      patient hospitalization.

PMID- 23882721
TI  - Response from Milan Milosevic.

PMID- 23882720
TI  - Betting on change: Tenet deal with Vanguard shows it's primed to try ACO effort,
      new payment model.
AB  - Tenet Healthcare Corp.'s acquisition of Vanguard Health Systems is a sign the
      investor-owned chain is willing to take a chance on alternative payment models
      such as accountable care organizations. There's no certainty that ACOs will
      deliver the improvements on quality or cost savings, but Vanguard Vice Chairman
      Keith Pitts, left, says his system's Pioneer ACO in Detroit has already achieved
      some cost savings.

PMID- 23882722
TI  - Surgical options for patellar stabilization in the skeletally immature patient.
AB  - Patella dislocation is a common injury in children and adolescents and occurs at
      a rate of 29 to 43 per 100,000 among the 10- to 17-year-olds. The variety and
      types of patellar instability seen in a pediatric orthopedic population may
      differ slightly from those seen in an adult clinic. Four main types of pediatric
      patellar instability exist and include: posttraumatic, syndromic, obligatory,and
      fixed. Over 100 surgical techniques have been proposed to treat the various types
      of patellar instability. This review intends to discuss the techniques and
      outcomes of surgical reconstructions accepted and utilized in the skeletally
      immature patients.

PMID- 23882723
TI  - [Survival of small businesses].

PMID- 23882724
TI  - CMS's proposed rule implementing the ACA-mandated Medicaid DSH reductions.
AB  - State Medicaid programs make Medicaid disproportionate share hospital (DSH)
      payments to hospitals to help offset costs of uncompensated care for Medicaid and
      uninsured patients. Unlike most Medicaid spending, annual DSH allotments for each
      state are capped. Under the Patient Protection and Affordable Care Act of 2010
      (ACA), DSH payments will decrease starting in fiscal year (FY) 2014 and
      continuing through FY 2020. This paper describes the proposed rule for reducing
      these federal allotments, which was released on May 15, 2013, by the Centers for
      Medicare & Medicaid Services (CMS). Comments on the proposed rule are due July
      12, 2013.

PMID- 23882725
TI  - Exclusion of orphan drugs for certain covered entities under 340B Program. Final
      rule.
AB  - HHS is issuing this final rule to clarify how section 340B(e) of the Public
      Health Service Act (PHSA) will be implemented. The final rule applies section
      340B(e) of the PHSA only to drugs transferred, prescribed, sold, or otherwise
      used for the rare condition or disease for which the orphan drug was designated
      under section 526 of the Federal Food, Drug, and Cosmetic Act (FFDCA). The final
      rule also sets forth that it is the responsibility of the 340B covered entity to
      maintain auditable records that demonstrate compliance with the terms of the
      orphan drug exclusion requirements. This rule will provide clarity in the
      marketplace, maintain the 340B savings for newly-eligible covered entities, and
      protect the financial incentives for manufacturing orphan drugs designated for a
      rare disease or condition as indicated in the Affordable Care Act and intended by
      Congress.

PMID- 23882726
TI  - [Comparative evaluation of acid-fast staining for the detection of Mycobacterium
      fortuitum--clinical performance of fluorescent and Ziehl-Neelsen staining].
AB  - OBJECTIVE: Fluorescent staining is of paramount importance, not only for
      confirming the presence of mycobacteria in a given specimen but also for
      providing an estimated growth quantification. In this study, for rapidly growing
      Mycobacterium fortuitum, we evaluated the effectiveness of a rapid fluorescent
      staining method employing auramine-rhodamine (AR) fluorescent stain and acridine
      orange (AO) fluorescent stain compared to that of the standard Ziehl-Neelsen (ZN)
      stain currently in use in our laboratory. METHOD: We evaluated the acid-fast
      nature of M. fortuitum strain ATCC6841 and 42 clinical isolates from each patient
      diagnosed at NHO Kinki-chuo Chest Medical Center. These isolates were
      preliminarily identified as M. fortuitum using DNA-DNA hybridization (DDH
      Mycobacteria; Kyokuto Pharmaceutical, Tokyo, Japan). These isolates were further
      identified by comparative sequence analysis of the ITS regions and the partial
      16S rRNA gene. RESULTS: A total of 26 M. fortuitum strains (61.9%) demonstrated
      the lack of an acid-fast nature by AR staining, and slightly fewer demonstrated
      the same by AO staining. Sequence analysis of these 42 clinical isolates led to
      the identification of 35 M. fortuitum subsp. acetamidolyticum isolates (83.3%)
      and 7 closely M. fortuitum isolates. DISCUSSION: This work reported the loss of
      the acid-fast nature of specific M. fortuitum strains. It is likely that both the
      specific cell envelope of M. fortuitum and the staining mechanics could have been
      responsible for the loss of the acid-fast nature since the 2 different
      fluorescent stains yielded the same results. M. fortuitum is a mycobacterium
      species that does not stain with the commonly used fluorescence microscopy
      technique. Therefore, we suggested the use of an identification scheme for these
      organisms that employs ZN staining and the study of cultural characteristics
      (growth rate, temperature, and pigment production).

PMID- 23882727
TI  - [A study of relapse/recurrence cases after surgical treatment for patients with
      pulmonary nontuberculous mycobacteriosis].
AB  - PURPOSE: This is a retrospective study on relapse/recurrence of surgical cases of
      pulmonary nontuberculous mycobacteriosis (NTM). Surgical treatment was performed
      at one hospital and by one surgeon. METHOD: Fifty patients had undergone surgical
      treatment from August 2004 to July 2011 in hospital. From this group, 37 patients
      were selected after one year, and of these, 9 patients had a relapse/recurrence
      (group A) and the others (28 patients without relapse/recurrence, group B). Data
      was recorded about their age, gender, pre-operative image score, cavernous
      lesions, residual lesions after operation, drugs of pre-operative chemotherapy,
      the duration of pre-operative chemotherapy, the duration of any follow-up after
      operation, type of mycobacteria, the results of bacterial cultivation of surgical
      specimens, type of mycobacterium and operative procedure. RESULT: Three factors,
      the result of bacterial cultivation of surgical specimens, duration of
      chemotherapy before operation and existence of residual lesions, showed a
      significant difference statistically. No case with major surgical complication
      and hospital death was recognized. CONCLUSION: The visible foci should be removed
      as thoroughly as possible. Pre-operative chemotherapy should not be continued
      unnecessarily, and surgical treatment should be chosen at an early stage. The
      results of bacterial cultures of surgical specimens could be very useful for
      predicting the possibility of relapse/recurrence after operation. Surgical
      treatments of our patients were carried out safely. However, as the patients have
      a risk of relapse/recurrence, they require careful monitoring and post-operative
      chemotherapy over along period.

PMID- 23882728
TI  - [Outbreak of extensively drug-resistant pulmonary tuberculosis in a hemodialysis
      facility].
AB  - We experienced an outbreak of extensively drug-resistant pulmonary tuberculosis
      (XDR-TB) in a hemodialysis facility. The primary case involved a 51-year-old male
      hemodialysis patient, with a history of treatment for Mycobacterium tuberculosis
      infection seven years previously. There was no drug resistance, and the patient
      completely recovered after undergoing treatment with isoniazid (INH), rifampicin
      (RFP) and ethambutol (EB). He was admitted to another hospital due to a
      recurrence of pulmonary tuberculosis in June 2006. At first, he was treated with
      HRS [INH, RFP and streptomycin (SM)]; however, the drug regimen was changed to
      INH, EB, levofloxacin (LVFX) and kanamycin (KM) in August following the results
      of a drug susceptibility test. Although the patient was receiving outpatient
      tuberculous therapy, he was readmitted in June 2007 due to relapse and conversion
      of a sputum culture to positive status. Additionally, the XDR-TB organism was
      identified. Following these events, five staff members of the hemodialysis
      facility and a member of the patient's family were diagnosed with XDR-TB
      infection. The staffs who were infected with XDR-TB had worked in the same
      dialysis room, drug resistance was found in all cases and drug resistant gene
      mutations were found in three cases; therefore, we considered this to be an
      outbreak. As XDR-TB infection was suspected in all cases, no patients took drugs
      to treat latent tuberculosis infection (LTBI). Regarding the causes of the
      outbreak, the first is the delay of four months in making a diagnosis of re
      exacerbation of tuberculosis. Second, in Case 2, the patient developed laryngeal
      and tracheobronchial tuberculosis after first being diagnosed with asthma, and
      the tuberculosis diagnosis was delayed. Third, the sputum smear of Case 2 was
      strongly positive. There is only one previously reported outbreak of XDR-TB in
      Japan; therefore, we consider this outbreak to be educational.

PMID- 23882729
TI  - [Primary nasopharyngeal tuberculosis].
AB  - A 59-year-old female was complaining of sore throat, right otorrhea, and hearing
      impairment. There were no abnormal findings suggestive of pulmonary tuberculosis
      on her chest XP and CT. Nasopharyngoscopic examination detected a lesion coated
      with white mass on her nasopharynx, and a biopsy-specimen from this lesion
      revealed histopathological findings compatible with tuberculosis and the presence
      of acid-fast bacilli. PCR was positive for Mycobacterium tuberculosis complex.
      Therefore, we diagnosed the case as primary nasopharyngeal tuberculosis and
      treated her by 4-drug combination regimen with daily isoniazid, rifampicin,
      ethambutol and pyrazinamide. Later, low degree of resistance was noticed,
      isoniazid was replaced by levofloxacin. After the anti-tuberculosis chemotherapy,
      her symptoms almost completely diminished and the mass in her nasopharynx
      disappeared. As far as we can search, 23 Japanese cases of primary nasopharyngeal
      tuberculosis, including this case, have been reported in the literatures. We
      summarized the clinical features of these cases in Table. Nasopharyngeal
      tuberculosis is a rather rare disease. But, recently, due to the advances in
      diagnostic technology, the number of the case-reports has been increasing.
      Difficulties in detecting tubercle bacilli in nasopharyngeal lesion sometimes
      delayed definite diagnosis and treatment. If a patient complains the symptoms
      compatible with this disease, such as sore throat, pharyngeal pain and otorrhea,
      which are refractory to the general antibiotic therapy, we should be aware of the
      existence of this disease and repeat bacteriological and/or molecular
      examinations to prove tubercle bacilli to be able to start timely anti
      tuberculosis chemotherapy.

PMID- 23882730
TI  - [Tuberuculosis annual report 2010 (10)--treatment outcomes].
AB  - Evaluation of treatment outcomes among tuberculosis (TB) patients using cohort
      analysis is an essential part of TB control programs. In Japan, treatment
      outcomes are automatically classified into 15 outcome groups according to a
      preset computerized algorithm. The treatment outcomes of new sputum-smear
      positive pulmonary TB (PTB) cases in 2009 (n = 8,772) were classified as follows:
      (a) Treatment success (a combination of "Cure" and "Treatment completed"), 51.7%;
      (b) Dead, 19.3%; (c) Treatment failure, 0.9%; (d) Default, 3.7%; (e) Transfer
      out, 3.3%; (f) Still on treatment after 12 months, 10.8%; and (g) Unclassified,
      10.3%. Among new sputum-smear positive PTB patients registered in 2007, 2008, and
      2009, the proportion removed from the tuberculosis register because of death by
      the end of the following year was 25.7%, 26.4%, and 26.9%, respectively. Among
      the new sputum-smear positive PTB patients registered in 2009 who died within 1
      year of treatment commencement (n = 2,102), 37.7% died within 1 month, 52.0%
      within 2 months, and 62.3% within 3 months.

PMID- 23882731
TI  - Pattern electroretinogram (PERG) in the early diagnosis of optic nerve
      dysfunction in the course of Graves' orbitopathy.
AB  - PURPOSE: The present study was design to evaluate the pattern electroretinogram
      in the diagnosis of early changes in visual function of patients with Graves'
      orbitopathy without perimetrical signs of optic nerve neuropathy. MATERIAL AND
      METHODS: 19 eyes from ten patients, mean age 36 +/- 6.8 SD. comprising (7 F and 3
      M) with GO, affected by (1-4) NOSPECS severity class were enrolled in the study.
      22 eyes from eleven healthy volunteers served as a control. The pattern
      electroretinogram was recorded with TE-1000 headset electrode using PRIMUS 2,5
      (Tomey). The temporal frequency of PERG was 2 Hz and the check size was 10.
      Student's t-test was used for the statistical analysis of mean and standard
      deviations. Statistical significance was assumed at p < 0.05 for all analyses.
      Cut-off points, sensitivity and specificity of the pattern elektroretinogram
      parameters assessed by receiver operating characteristic curves were performed by
      Medcalc RESULTS: In patients with Graves' orbitopathy a significantly decreased
      P50 amplitude was found (2.04 +/- 0.99 vs. 2.69 +/- 0.88 in healthy controls).
      Receiver operating characteristic curves analysis revealed a high sensitivity of
      P50 amplitude and N95-P50 amplitude for discrimination between Graves'
      orbitopathy and healthy group (78.9% and 81.8%, respectively). The specificity of
      P50 amplitude was fairly high (63.6%) while N95-P50 amplitude was rather low
      (47.4%). CONCLUSIONS: The reduction of the P50 amplitude could be a marker of an
      early ischemic optic nerve dysfunction in patients with Graves' orbitopathy. The
      evaluation of the pattern electroretinogram P50 and N95-P50 amplitude might be a
      fairly sensitive test for screening dysthyroid optic neuropathy.

PMID- 23882732
TI  - Botulinum toxin injection as primary treatment for esotropia in patients with
      cerebral palsy.
AB  - PURPOSE: Botulinum toxin type A is a potent neurotoxin that blocks the release of
      acetylocholine at the neuromuscular junction of cholinergic nerves. Cerebral
      palsy is cause of ocular disorders. There is an increased presence of strabismus,
      refractive errors, and reduced visual acuity. The purpose of this study was to
      assess the efficacy of botulinum toxin injection in the treatment of esotropia in
      patients with cerebral palsy. MATERIAL AND METHODS: Seven patients were included
      in the study. All patients had a full ophthalmic examination on initial visit,
      including cycloplegic refraction and duction. The angle of esotropic deviation at
      distance was recorded in prism diopters. The botulinum toxin type A was
      administered into the medial rectus muscle under general anesthesia. RESULTS:
      Mean age of the patients was 12 years. The mean angle of deviation pretreatment
      was 36.6 PD. Successful motor alignment (orthotropia +/- 10 PD) was achieved in
      the botulinum toxin type A group in 57.1% of patients. CONCLUSIONS: The use of
      botulinum toxin in the treatment of esotropia in children and adolescents with
      cerebral palsy is an alternative to conventional surgical therapy.

PMID- 23882733
TI  - Bevacizumab intravitreal injections in the treatment of diabetic macular oedema.
AB  - PURPOSE: To estimate effectiveness of bevacizumab intravitreal injections in the
      treatment of diabetic macular oedema. MATERIAL AND METHODS: The perspective study
      included 22 eyes in 22 patients with clinically significant diabetic macular
      oedema confirmed by fluorescein angiography and optical coherence tomography.
      Mean age of the patients was 60.6 +/- 12.4 years, while mean diabetes duration
      was 16.0 +/- 9.3 years. Vision acuity (expressed in logMAR scale), as well as
      anterior and posterior part of the eye were evaluated. Central retinal thickness
      was measured with the use of optical coherence tomography Topcon 3D OCT 1000
      apparatus before and 3 weeks following each injection. Bevacizumab was
      administered intravitrealy in the dose of 1.25 mg/0.05 ml at monthly intervals.
      10 patients were administered 3 injections, 5 patients - 2, while 7 - only 1
      injection. The injection therapy was discontinued when the patients gained full
      vision acuity or when central retinal thickness was reduced to <250 microm.
      Statistical analysis of the results was performed with the use of Wilcoxon test,
      with significance p <0.05. RESULTS: Mean vision acuity prior to the therapy
      amounted to 0.50 (0.15-1.50) logMAR and after the first injection improved to
      0.40 (0.00-1.30) logMAR (p = 0.044). Further improvement was observed after
      subsequent injections. As regards patients who were administered 3 injections,
      mean vision acuity observed after further injections improved significantly from
      0.50 (0.15-1.50) logMAR prior to the treatment to: 0.45 (0.1-1.3) (p = 0.078),
      0.35 (0.00-1.30) (p = 0.011), 0.25 (0.05-1.20) (p = 0.007) and 0.30 (0.10-0.70)
      logMAR (p = 0.018). The first injection caused no reduction of retinal thickness 
      368 microm (234-708) vs. 389 (236-642) microm (p=0.602). However, ollowing
      further injections decreased retinal thickness compared to the initial values;
      yet the differences were not significant. Retinal thickness following three
      injections amounted to: 407 (312-701) microm prior to the treatment, 441 (323
      634) microm one month after the first injection (p = 0.959), 340 (281-679) one
      month after the second injection (p = 0.126), 331 (244-568) one month after the
      third injection (p = 0.086) and 348 (147-627) three months after the third
      injection (p = 0.176). CONCLUSIONS: Intravitreal bevacizumab injections in
      patients with diabetic macular oedema caused a significant improvement of vision
      acuity and a significant reduction of central retinal thickness.

PMID- 23882734
TI  - [Morphology of the optic nerve disc in eyes with myopia in correlation to the
      refractive error].
AB  - PURPOSE: To asses morphology of the optic nerve disc in correlation to the
      refractive error in eyes with myopia. MATERIAL AND METHODS: The examined group
      consisted of 47 patient (84 eyes), age 20 to 36 years (mean age 28 +/- 4,5), with
      refractive error -4.00 Dsph to -14.25 Dsph +/- 0.75 Dcyl. This group was divided
      into two subgroups according to value of refractive error. The control group
      contained matched persons according to the gender and age. The basic
      ophthalmological examination and scanning laser ophthalmoscopy with HRT retinal
      tomography were performed. RESULTS AND CONCLUSIONS: In patients with moderate and
      high myopia there was an increase of the optic nerve disc area and volume, and
      area and volume of the neuroretinal rim in comparison to the emmetropic eyes. In
      patients with high myopic eyes there was an increase of the area and depth of the
      optic nerve cup. The area of the optic nerve disc and the neuroretinal rim was
      found to be bigger as the refractive error increased in group of moderate myopia.
      There were no statistically significant differences of thescanning laser
      ophthalmoscopy with HRT parameters (C/D AR and L C/D R) of the cup to the area
      and the diameter of the disc between myopic and emmetropic eyes.

PMID- 23882735
TI  - [Vitreomacular adhesion in HD-OCT images in the age-related macular
      degeneration].
AB  - PURPOSE: The aim of this study was to evaluate an incidence of the vitreomacular
      adhesion in patients with age-related macular degeneration. MATERIAL AND METHODS:
      We examined 472 eyes in 241 patients (136 W/ 105 M) in age of 54-92 years (mean
      62.6 years +/- 8.5) with dry or wet age-related macular degeneration using Cirrus
      HD-OCT (Zeiss) macular cube 512x128 program or 5-line pro-gram. RESULTS:
      Vitreomacular adhesion was observed in 139 eyes with dry age-related macular
      degeneration (29.4%, p=0.000*), in 101 eyes with drusen (21.4%, p=0.000*), in 38
      eyes with retinal pigment epithelium alterations (8%, p=0.202), in 278 eyes with
      wet age-related macular degeneration (58.9%, p=0.001*), in 21 eyes with pigment
      epithelial detachment (4.4%, p=0.303), in 161 eyes with choroidal
      neovascularzation (34. 1%, p=0.031*/ and in 96 eyes with scar (20.4%, p=0.040*).
      CONCLUSIONS: Probably, vitreomacular adhesion alone is not able to induce age
      related macular degeneration, but it may be associated with choroidal
      neovascularization development, it can contribute to exudate formation and
      choroidal neovascularization, it may induces or sustains a chronic low-grade
      inflammation in the macula region.

PMID- 23882736
TI  - [Thrombophilia - a risk factor of retinal vein occlusion?].
AB  - To evaluate thrombophilia as a risk factor of retinal vein occlusion in
      comparison with a control group and a general polish population. MATERIAL AND
      METHODS: Fifty nine consecutive patients with retinal vein occlusion were
      enrolled in this study. The diagnosis of retinal vein occlusion was based on the
      presence of typical findings in the eye fundus, fluorescein angiography, and
      optical coherence Stomography. Control group consisted of 59 subjects matched for
      age, sex, body mass index (BMI), medications, and cardiovascular risk factors. In
      all patients the following thrombophilic factors were evaluated: factor V
      mutation, 20210A prothrombin mutation, MTHFR (methy
      lenetetrahydrofolatereductase) mutation C677T, protein C and free protein S
      level, antithrombin activity, factor VIII activity, anty-beta2 glikoprotein I
      antibodies level, anticardiolipin antibodies level, the presence of lupus
      anticoagulant, total homocysteine concentration. RESULTS: In both groups with
      retinal vein occlusion and control group a high incidence of factor V Leiden was
      observed: 10.2% and 15.6%, respectively. In one patient the presence of 20210A
      prothrombin mutation was noted and in one the deficiency of free S protein was
      observed. Antiphospholipid antibodies were present in 11.8% of cases and factor
      VIII concentration > 150% in 3% of patients with retinal vein occlusion. In 8.5%
      of patients with retinal vein occlusion genotype TT MTHFR was present. Hyper
      homocysteinemia was found in 5 cases with retinal vein occlusion (8.5%) and in 7
      in a control group (11.9%). In a venous blood of patients with retinal vein
      occlusion homocysteine level was lower by 14.5% as compared with a control group
      (9.4 [7.0-11.3] vs. 11.0 [9.4-12 .8] micromol/l, p = 0.001). CONCLUSIONS: The
      results of thrombophilia screening in patients with retinal vein occlusion showed
      no statistical differences as compared with a control group matched for age, sex,
      and cardiovascular risk factors. However patients with retinal vein occlusion
      showed statistically significant lower serum homocysteine concentration as
      compared with a control group. Two times higher prevalence of factor V Leiden was
      observed in patients with retinal vein occlusion than in Polish general
      population.

PMID- 23882737
TI  - [Influence of cancer chemotherapy on conjunctival epithelium and goblet cells].
AB  - PURPOSE: Evaluation of different types of chemotherapy schemes administered in
      lung, breast and bowel cancer on conjunctival epithelium and goblet cells
      morphology. MATERIAL AND METHODS: 36 patients (72 eyes) were enrolled to the
      study. Patients were divided into three groups depending on type of cancer and
      chemotherapy: group I - patients diagnosed with non- small cells lung cancer
      treated with PE schema (cisplatin, etoposide), group II - with breast cancer
      treated with FAC schema (fluorouracil, doxorubicin, cyclophosphamide), group Ill 
      bowel cancer treated with FU/LV schema (fluorouracil, leucovorin). Examinations
      were performed before chemotherapy and after Il'th, IV'th, VI'th chemotherapy
      cycle. Conjuntival specimen were obtained with exfoliative cytology, stained with
      PAS and hematoxyline. RESULTS: Statistically significant deterioration of
      conjunctival epithelium and goblet cells in all the groups in each time of
      examination (p<0.001) was observed. Alterations were aggravated with duration of
      chemotherapy. Before chemotherapy all the patients had normal epithelium and
      goblet cells (grade 0 or 1 according to the Nelson's scale). Conjunctival cells
      status gradually deteriorated and altered from the normal glandular epithelium to
      the squamous cells epithelium through the process of squamous metaplasia. In
      further chemotherapy cycles each patient (1,0 fraction) had abnormal morphology
      of epithelium and goblet cells (grade 2 or 3 of Nelson's scale). CONCLUSIONS:
      Chemotherapy induces squamous metaplasia of epithelium and the reduction of
      number of conjunctival goblet cells. This abnormalities were time dependent and
      increased with duration of chemotherapy and were not depended on type of
      chemotherapy scheme.

PMID- 23882738
TI  - [Orthokeratology in myopic children].
AB  - Orthokeratology is reversible clinical procedure which can reduce myopia using
      contact lenses made of high gas permeable material with 4 curves reverse geometry
      shape. PURPOSE: The aim of the paper is to evaluate vision acuity and progression
      of myo,ia and corneal curvature during use of overnight RGP lenses. MATERIAL AND
      METHODS: The studies have been peforrmed in 132 patients (264 eyes) in age 5 - 18
      years (average 12.5 years) with myopia from -1.50 Dsph to -5.50 Dsph and
      astigmatism from 0.25 Dsph to 1.25 Dsph. In all patients cornea radius (automatic
      keratorefractometer) and coreal refractive power (coreat topography) was measured
      before and after 3 months of we- se ot aring during night RGP lenses. Refraction
      was measured with the use of autokeratorefraktometer after 2 to 6 years of
      wearing lenses. RESULTS: In all patients reduction of corneal refractive power
      (on average 3.05 Dsph) and increase of corneal radiuses (on average 0.4 mm) has
      been observed. After 2 to 6 years of wearing during night RGP lenses refraction
      was the same in 48.5% of children, worsened in 31.8% of -0.50 Dsph and progressed
      of -1.00 Dsph in 19.7% of patients. CONCLUSION: Orthokeratology reduces myopia
      due to temporary changes in corneal curvature. orthokeratology, myopia, corneal
      radius, corneal topography.

PMID- 23882739
TI  - [Posterior lamellar keratoplasty with DSEK technique and use of the Tan EndoGlide
      - short-term results].
AB  - PURPOSE: To present the differences in surgical technique of DSEK (Descemet's
      Stripping Endothelial Keratoplasty) with the use of Tan EndoGlide (Coronet, UK)
      and Busin Glide (Moria, FR). Short-term results will also be presented, MATERIAL
      AND METHODS: DSEK was performed in 24 eyes, in 8 cases the surgery was combined
      with cataract phacoemulsification and lOL implantation. Surgery course and 6
      months postoperative results of first 12 eyes performed with the use of Tan
      EndoGlide were compared with 12 consecutive eyes preformed with Busin Glide.
      RESULTS: Tan EndoGlide provided much more stable anterior chamber, donor tissue
      unfolding process was better controlled but the incision was wider incision.
      Surgically induced mean refractory cylinder 6. months after the surgery was 1.56 
      1.15 Dsph in Tan EndoGlide group and 1.18 +/- 1.10 Dsph in Busin Glide group (P
      <0.05). The endothelial cell loss was 20.5% and 21.12% respectively (P>0.05).
      Mean CDVA was 0.65+/- 0.27 and 0.63 +/- 0.25, respectively (P>0,05).
      Statistically significant differences in intra- and post-operative complications
      between both groups were not found. CONCLUSIONS: The Tan EndoGlide used during
      posterior lamellar keratoplasty with DSEK technique is a good alternative to
      currently used methods. It provides better stabilization of the anterior chamber,
      however its use is linked with higher postoperative astigmatism in comparison
      with Busin Glide. The visual outcomes and endothelial cell loss 6 months after
      the surgery were similar in both groups.

PMID- 23882740
TI  - Squamous cell carcinoma of the lower eyelid penetrating into the orbit - case
      report.
AB  - The aim of our study is to report a case of pigmented squamous cell carcinoma of
      the palpebral conjunctiva referred to our clinic because of eye pain. A 86 year
      old patient suffering from eye pain due to a lower right eyelid tumour was
      admitted to our department. The basic ophthalmic examination and CT scans of
      orbits were performed. A lesion was surgically removed and histologically
      examined. The best corrected visual acuity in the left eye was 0.1 and there was
      light perception in the right eye. Ocular examination of the right eye revealed
      hard, pigmentendand vascularized mass in the lower palpebral conjunctiva
      penetrating into the lid margin and the orbit, epiphora, bacterial conjunctivitis
      and vascularized corneal scar with adherent leucoma. Histopathologic examination
      revealed a squamous cell carcinoma. The accurate diagnosis and correct management
      of the malignant eyelid tumours always requires histological examination.
      Surgical removal and additional radiotherapy in the case of extensive SCC
      conjuctival lesions is necessary. .

PMID- 23882741
TI  - Clinical picture of multifocal chorioretinitis caused by mycobacterium
      tuberculosis - case report.
AB  - We present clinical picture of unusual case, of multifocal chorioretinitis due to
      tuberculosis. Twenty years old female was admitted to ENT department with
      cerivical lymphadenopathy, profound dolorous tonsils enlargment resembling
      antibiotic resistant purulent tonsillitis and nasopharyngeal masses. The patient
      also reported transient vision disturbances. Lymph node and Waldeyer's ring
      biopsy revealed tubercular granulomatosis with caseation, Gramm(+) bacteria, and
      Mycobacterium tuberculosis DNA presence by polymerase chain reaction testing.

PMID- 23882742
TI  - [Cataract surgery in a patient with megalocornea - a case report].
AB  - PURPOSE: 10 describe a rare case ot a patient wiTh megalocorneas wno underwent
      cataract surgery. MATERIAL AND METHODS: A 52 years old patient with extremely
      wide corneas 16 mm in diameter in both eyes, was admitted to our department with
      cataract diagnosis. Four other male members of his family are known to have
      megalocorneas. This suggests X-linked recessive inheritance. The visual acuities
      were; 0.9 with correction -3.00 Dsph in the right eye and 0.6 with correction 
      5.50 Dsph in the left eye. Mosaic corneal dystrophy and slight iridodonesis was
      found in both eyes. Posterior subcapsular cataracts were seen in both eyes with
      predominance in the left eye. Moreover, flat peripheral retinal detachment in the
      lower part of the eye fundus was found, which was presumably long-lasting.
      Phacoemulsification through the clear corneal temporal micro-incision of 1.8 mm
      and the foldable intraocular lens IOL) implantation in the left eye were
      performed. The IOL refractive power was calculated with 101 Master and with
      standard contact ultrasound biometry. Preventive laser photocoagulation of the
      retina was performed in the right eye. RESULTS: No intraoperative and
      postoperative complications were observed. Two weeks after cataract surgery
      corrected visual acuity in the left eye was ii] with correction + 1.00 Dsph. The
      patient was very satisfied with the surgery result. CONCLUSIONS:
      Phacoemulsification with an implantation of foldable 101 in patients with
      megalocornea may be a safe procedure with very good functional results. Precise
      IOL power calculation may be difficult to achieve.

PMID- 23882743
TI  - [Ocular manifestation of langerhans' cells histiocytosis - case report].
AB  - PURPOSE: To present a case of a young female suffering from Langerhans' cells
      histiocytosis of the lungs with ocular involvement. MATERIAL/ RESULTS: Patient
      was primarily admitted to the ophthalmology department due to bilateral mature
      cataract. Phacoemulsification did not improved visual acuity. Based on
      ophthalmological examination, spectral coherence tomography scans and fundus
      angiography and previous medical history, concomitant advanced changes e.g. optic
      nerve atrophy and severe obliteration of retinal vessels was revealed
      CONCLUSIONS: Our case presents one of rare ophthalmic localization of Langerhans,
      cells histiocytosis within vessels wall and/ or optic nerve that can be
      potentially the reason of that arterial and vein obliteration and optic nerve
      atrophy.

PMID- 23882744
TI  - [Treatment of cystoid macular edema with bevacizumab in course of Irvine-Gass
      syndrome].
AB  - PURPOSE: To determine clinical effect of intravitreal bevacizumab (Avastin) in
      patients with cystoid macular edema after cataract surgery. MATERIAL AND METHODS:
      Four eyes of four patients treated with 1 intravitreal injection of 1.25 mg
      Avastin. In three cases duration of cystoid macular edema was less then 4 months,
      in one eye cystoid macular edema was chronic (more than 4 months). Visual acuity
      and clinical effect in spectral optical coherence tomography (central retinal
      thickness and fovea anatomy) was examined before and after intravitreal
      injection. RESULTS: Visual acuity improved in 3 of 4 patients. In acute cystoid
      macular edema final visual acuity was 0.8-0.9, in chronic cystoid macular edema
      patient visual acuity improved from 0.05 to 0.2. In 3 of 4 patients central
      retinal thickness decreased and fovea anatomy was normalized. In patient with no
      clinical and anatomical improvement spectral optical coherence tomography
      examination revealed epiretinal membrane. CONCLUSIONS: Intravitreal Avastin may
      be successful treatment in most Irvine-Gass syndrome cases. The condition that
      exclude patients from bevacizumab treatment is horizontal (epiretinal membrane),
      and vertical traction revealed in spectral optical coherence tomography.

PMID- 23882745
TI  - Present-day conservative treatment retinopathy of prematurity.
AB  - Retinopathy of prematurity occurs in prematurely born babies. Etiology of disease
      is multifactorial and frequency of retinopathy of prematurity diagnosis
      increases. Retinopathy is one of causes for major loss of vision and amaurosis in
      newborns around the world. Low efficacy of treatment leads to necessity for
      looking for new solutions and modern therapy use in treatment of this disease. So
      far, therapies used are: laser and cryotherapy and cases of retina detachment,
      the course is combined with surgical procedures of sclera and vitrectomy. The aim
      of the paper was detailed observation of available literature concerning new
      methods of management in retinopathy of prematurity. Newest reviews on role of
      vascular endothelial growth factor secreted under the influence of hypoxia
      indicate that it takes part in angiogenesis and neovascularization. Thus, in
      retinopathy of prematurity management vitreous application of vascular
      endothelial growth factor inhibitors such as ranibizumab, bevacizumab are used as
      supplement or treatment combined with laser therapy or surgical procedures,
      however there are many controversies on this form of treatment. Recently there
      has been an interest in vitreous application of Triamcinolon and other
      experimental substances inhibiting fibro-vascular proliferations in mouse models
      of retinopathy of prematurity. Hopes connected with high efficacy of retinopathy
      of prematurity treatment are also related to use of gene therapy, beta-blockers,
      supplementation with Omega-3 acids, matrix metalloproteinase-2 inhibitors, gold
      nanoparticles-GNP and anthrax lethal toxin.

PMID- 23882746
TI  - [The application of corneal collagen cross-linking in diseases other than
      keratoconus].
AB  - Corneal collagen cross-linking is a method of treatment using ultraviolet
      radiation UVA and photosensitizing substance riboflavin to strengthen the
      chemical connections between the collagen fibers of corneal stroma. This
      treatment is focused on halting the progression of the diasases, called ectasias,
      characterized by irregular curvature and diminished thickness of the cornea. The
      most common indication for corneal collagen cross-linking is keratoconus.
      However, this technique may be also applied to pathologies other than
      keratoconus. The aim of this paper is to review the applicilcability of corneal
      collagen cross-linking in other conditions than keratoconus. Specifically, the
      conditions such as pellucid marginal degeneration, post refractive surgery
      ectasia as well as combined corneal collagen cross-linking and topography-based
      photorefractive keratectomy for topographies indicating forme fruste keratoconus
      are discussed. In addition, the effects of-corneal collagen cross-linking-as an
      adjunctive therapy in keratitis, corneal ulcers and corneal edema in bullous
      keratopathy are considered. The authors highlight the importance of treatment in
      clinical practice and the potential application of the treatment and modification
      of the protocols in the treatment of corneal diseases other than keratoconus.

PMID- 23882747
TI  - Folate grafted Prussian Blue entrapped with gadolinium(III) as a new contrast
      agent for tumor-targeted magnetic resonant imaging.
AB  - A new generation of magnetic resonant imaging (MRI) contrast agents will
      simultaneously possess characteristics of high relaxivity, biotargeting ability
      and nontoxicity, referring that they are helpful to acquire better contrast
      imaging in the region of interest (e.g., tumors) without health risks. Colloidal
      Prussian blue with quasi-zeolite structure was introduced as a new type of
      nanosized scaffold to entrap Gd(III) ions via ion exchange and folate, one kind
      of cancer-targeting ligand, was intentionally grafted on its surface. The
      nanoparticulate contrast agent has T1 relaxivity of up to 23.9 mM(-1) s(-1). In
      vivo MRI illustrated a clear contrast enhancement specifically on the ovarian
      tumors transplanted on mice at a low dose. Furthermore, the contrast agent is
      stable and free of cytotoxicity. Therefore it might be a promising new MRI
      contrast agent for clinical applications.

PMID- 23882748
TI  - Detection of K-Ras oncogene using magnetic beads-quantum dots in microfluidic
      chip.
AB  - Recently quantum dots (QDs) have been extensively used in the field of
      biotechnology. QDs have merits of wide selection of emission wavelength and
      exceptional stability against photo bleaching over conventional organic
      fluorophores and are used in cell imaging, biomarker, and fluorescence resonance
      energy transfer (FRET) sensor. Magnetic beads have been used as solid support in
      microfluidic devices to trace bio-molecules. In this study, Polydimethylsiloxane
      (PDMS) based microfluidic chips were prepared for the detection of K-Ras oncogene
      by using QDs-DNA conjugate. K-Ras oncogene can be detected by fluorescence
      quenching in microfluidic chip. Carboxylated CdSe/ZnS QDs (emission wavelength:
      605 nm) could bind to magnetic beads of polystyrene/divinyl benzene via EDC/NHS
      crosslinking reaction. The fluorescence from QDs could be quenched by
      intercalating dye (thiazol orange dimers: TOTO-3) after hybridization with target
      DNA and probe DNA in the channel of microfluidic chip. The fluorescence intensity
      change of QDs after hybridization in microfluidic chip has been studied.

PMID- 23882749
TI  - Quantitative analysis of H5N1 DNA hybridization on nanowell array electrode.
AB  - A nanowell array electrode-based electrochemical quantitative system without
      amplification was developed and applied for the detection of H5N1 target DNA. An
      18-mer probe was immobilized on a nanowell array electrode with a diameter of 500
      nm, which was coated with streptavidin and a self-assembly monolayer (SAM). The
      surface properties of probe DNA hybridization with complementary target DNA were
      characterized using atomic force microscopy (AFM) and electrochemical impedance
      spectroscopy (EIS). The AFM image shows that the depth of nanowell was reduced
      from 200 nm to 15 nm due to the formation of a DNA hybridization complex on the
      streptavidin/SAM structure. Differences in charge transfer resistance
      (deltaR(ct)) in EIS upon hybridization of the probe DNA with complementary target
      DNA were analyzed and used for the quantitation of H5N1 DNA. This approach shows
      that the quantitative analysis of H5N1 DNA ranging from 1 pM to 1 microM DNA is
      possible on a nanowell array electrode.

PMID- 23882750
TI  - Rapid detection of specific genes from human genomic DNA using the microbead
      quantum dot complexes in microfluidic chip.
AB  - In the clinic, it is important to prepare for single stranded DNA from genomic
      DNA to detect the target gene. In this study, we have investigated the detection
      of single stranded DNA (ssDNA) obtained by ultrasonication of human genomic DNA
      via fluorescence quenching on microfluidic chip with pillars at the channel to
      entrap the microbead-QD complexes (MQCs). The QDs with carboxyl group bind to
      microbeads with amine group by EDC/NHS coupling reaction. The thiolated probe DNA
      conjugates strongly with the metal ions on the surface of QDs. The MQCs were
      packed into a chamber on the channel blocked by pillars. ssDNA and TOTO-3
      (intercalating dye) were introduced into the microchannel. After hybridization of
      probe DNA and target DNA, fluorescence quenching was observed at the surface of
      the MQDs by FRET between QD and TOTO-3. This experiment shows the possibility of
      rapid detection of genomic DNA from clinical samples via microbead-QD complexs on
      microfluidic chip.

PMID- 23882751
TI  - A cytotoxicity study of fluorescent carbon nanodots using human bronchial
      epithelial cells.
AB  - The labeling of living cells with carbon nanoparticles has been increasingly
      studied both in vivo and in vitro, but concerns about the potential cytotoxicity
      of these nanoprobes are also increasing. In this study, the fluorescent carbon
      dots (CDs) without surface modification was synthesized and evaluated for its
      cytotoxicity. Indicators including cell viability, total reactive oxygen species
      (ROS), glutathione, malondialdehyde and lactate dehydrogenase were assessed using
      human bronchial epithelial (16HBE) cell line. Our results showed that CDs
      preferred to locate on the surface of cells, which significantly increased the
      membrane permeability of 16HBE cells. CDs exposure could further induce oxidative
      stress, exhaust the antioxidant defenses of cells and finally lead to decreased
      cell viability. Therefore, surface modification of CDs is needed to minimize its
      cytotoxicity. The present work is useful for the development of new strategies
      towards the in vitro and in vivo applications of CDs for optical imaging and drug
      delivery.

PMID- 23882752
TI  - Calcium phosphate/octadecyl-quatemized carboxymethyl chitosan nanoparticles: an
      efficient and promising carrier for gene transfection.
AB  - Calcium phosphate (CaP) has been widely used as the vector for gene transfection
      in the past three decades. However, clinical application is still not popular due
      to the poor-controlling of DNA/CaP complexes preparation, cytotoxicity and its
      low transfection efficiency. In this study, a novel amphipathic octadecyl
      quatemized carboxymethyl chitosan (OQCMC) derivative from chitosan was combined
      with calcium phosphate to synthesize CaP/OQCMC nanoparticles (CaP/OQCMC NPs). The
      nanoparticles were 122-177 nm in diameter exhibited neutral zeta potential (from 
      0.115 mV to 0.216 mV), and they were applied as DNA vectors for DNA loading and
      in vitro transfection. The results showed that CaP/OQCMC NPs displayed high DNA
      loading capacity and enhanced transfection efficiency with extremely low
      cytotoxicity. In addition, both CaP and OQCMC are biocompatible and
      biodegradable, thus the as-prepared CaP/OQCMC NPs are promising in gene delivery.

PMID- 23882753
TI  - Regulation by bisoprolol for cardiac microRNA expression in a rat volume-overload
      heart failure model.
AB  - Emerging evidence suggests the involvement of altered microRNA (miRNA) regulation
      in heart failure pathogenesis. We established a rat volume-overload heart failure
      model, and examined miRNA expression in normal rats and in the heart failure
      model, both with and without treatment with bisoprolol. Using miRNA microarrays,
      we identified 46 differentially expressed miRNAs in the rat heart failure model
      compared with normal rats. We also identified 18 differentially expressed miRNAs
      following treatment of normal rats with bisoprolol. Treatment with bisoprolol
      reversed, to varying degrees, the expression of 10 of the 46 miRNAs whose
      expression was differentially expressed in the heart failure model. Bioinformatic
      category analysis of the predicted target genes of these 10 miRNAs suggested that
      several encode ion-binding proteins. Our results showed that bisoprolol
      intervention can significantly improve cardiac function and decrease myocardial
      reconstruction in chronic heart failure. These data suggest that the expression
      of many miRNAs changes during heart failure, and that bisoprolol may exert its
      cardioprotective effects in part by reversing the differential expression of some
      of these genes.

PMID- 23882754
TI  - Inflammatory and hyperalgesic effects of oxidized multi-walled carbon nanotubes
      in rats.
AB  - We evaluated local inflammatory activity of oxidized multiwalled carbon nanotubes
      in rat experimental models of acute inflammation (paw edema and hyperalgesia) by
      analyzing their toxicity in non-mesoendothelial tissues. Subcutaneous injection
      of the nanotubes induced paw edema, that was maximal in the first 2 h after
      administration at 0.1 mg/kg (43.25 +/- 3.8 AUC) and 1 mg/kg (30.1 +/- 1.8 AUC)
      compared to saline (18.32 +/- 02.05 AUC). The histopathological analysis showed
      acute inflammation characterized by vasodilatation, edema formation, neutrophil
      infiltrate and tissue damage. The nanotubes also elicited hyperalgesic response,
      seen by the increase of animal paw withdrawal that was maximal in the first 3
      hours. The data obtained at the 3rd h was: 75 +/- 9.3% (0.01 mg/kg), 58 +/- 8.3%
      (0.1 mg/kg) and 53 +/- 6.69% (1 mg/kg) in relation with saline (28 +/- 3.5%). In
      conclusion, the oxidized multiwalled carbon nanotubes elicit inflammatory and
      hyperalgesic effects associated to severe tissue damage in rats.

PMID- 23882755
TI  - Impact of surface nano-textured stainless steel prepared by focused ion beam on
      endothelial cell growth.
AB  - The modification of stent surfaces with nano-structures has the potential for
      limiting late stent restenosis. We report here the patterning of 316L austentitic
      stainless steel with arrays of nano-pits of two nominal diameters: 120 and 180
      nm. These nano-textured surfaces were prepared by focused ion beam milling. The
      influence of the ion beam current on the nano-features was investigated by
      scanning electron and atomic force microscopies. The optimum ion beam currents
      were 280 pA for 120 nm nano-pits and 920 pA for 180 nm nano-pits. The depths of
      the nano-pits formed were (65 +/- 24) nm (120 nm) and (84 +/- 36) nm (180 nm).
      This wide distribution of the depths is due to the polycrystalline nature of 316
      L stainless steel, which has a strong influence on the milling rates. Endothelial
      cells were grown in vitro on these substrates for 1, 3 and 5 days. The cells were
      viable for the duration of the cell culture on the nano-textured substrates.
      There was no significant difference in the adhesion and the proliferation based
      on the nano-pit diameter.

PMID- 23882756
TI  - Effect of microencapsulation of Lactobacillus plantarum 25 into
      alginate/chitosan/alginate microcapsules on viability and cytokine induction.
AB  - Lactobacillus plantarum 25 (LP25) encapsulated into alginate/chitosan/alginate
      (ACA) microcapsules (LP25-ACA MCs) prepared by an extrusion methods were
      characterized to assess their efficacy in oral delivery. The particle sizes of
      LP25-ACA MCs were 1.11 +/- 0.32 mm. The loading content of LP25 was 1.11 x 10(7)
      colony forming unit (cfu)/microcapsule and encapsulation efficiency was above
      98%. The viability of LP25 in ACA MCs was more than 65% in simulated gastric
      fluid (SGF, pH 2.0) and 75% in simulated small intestinal fluid (SIF, pH 7.2) up
      to 2 h. Encapsulated LP25 were completely released from LP25-ACA MCs in SIF and
      simulated colon fluid (SCF, pH 6.0) within 12 h and 8 h respectively. The
      viability of LP25 in ACA MCs till 5 weeks was above 58%, whereas viability of
      free LP25 stored at room temperature up to 5 weeks was zero. Besides, LP25-ACA
      MCs induced the secretion of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) from macrophages and dendritic cells showing the
      immunomodulatory effect of LP25. These findings demonstrate that the
      encapsulation of LP25 by ACA is a suitable strategy for oral delivery of
      probiotics.

PMID- 23882757
TI  - Physicochemical and biofunctional properties of crab chitosan nanoparticles.
AB  - The physicochemical and biofunctional properties of crab chitosan nanoparticles
      of two different sizes (Nano A and B) manufactured by dry milling method were
      evaluated for commercialization. The deacetylation degrees (DD) of Nano A, B and
      the control chitosan were 90.9, 93.0, and 92.7% respectively whereas their
      molecular weights (M(w)) were 43.9, 44.7 and 208.8 kDa. The average sizes of the
      dispersed Nano A, B and the control chitosan in cetyltrimethylammonium chloride
      were 735.9, 849.4 and 2,382.4 nm, respectively, which were lower than 1441.7,
      2935.6 and 6832.9 nm of the intact chitosans. Chitosan nanoparticles had mild
      tyrosinase, antioxidant and angiotensin I converting enzyme (ACE), but weak
      collagenase, elastase and beta-glucuronidase inhibitory activity. However, Nano A
      had strong alpha-glucosidase inhibitory activity, which was comparable to that of
      acarbose, a commercial alpha-glucosidase inhibitor. In addition, the minimum
      inhibitory concentrations (MICs) of chitosan and its nanoparticles ranged from 30
      to > 200 microg/mL against each four gram-positive and gram-negative bacteria.
      Therefore, crab chitosan nanoparticles could be used as a nutraceutical,
      cosmeceutical or pharmaceutical product.

PMID- 23882758
TI  - Micron- and nano-sized poly(N-isopropylacrylamide-co-acrylic acid) latex
      syntheses and their applications for controlled drug release.
AB  - Thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc))
      latex particles were prepared with and without sodium dodecyl sulfate (SDS)
      surfactant via an emulsion polymerization method. The P(NIPAAm-co-AAc) latex
      particle sizes were approximately 1.1 microm without SDS addition and the
      particle sizes were in the nanometer range (59 nm) with SDS at its critical
      micelle concentration (CMC) of 8 mM. We propose a scheme to demonstrate how the
      SDS concentration affects the synthesized latex particle size. The lower critical
      solution temperature (LCST) was hardly influenced by the SDS level but increased
      with the AAc concentration. The PNIPAAm-co-AAc latex particles were employed as
      thermo-sensitive drug carriers and 4-acetamidophenol was loaded to study the drug
      release rates from the nano-gels. The effective drug diffusion coefficients
      within the nano-gels varied as a function of particle size, AAc content, and
      temperature. The smaller or AAc-rich hydrogel particles provided sustainable drug
      release property and have potential use in biomedical applications.

PMID- 23882759
TI  - Anodic TiO2 nanotubular arrays with pre-synthesized hydroxyapatite--an effective
      approach to enhance the biocompatibility of titanium.
AB  - Electrochemically anodized TiO2 nanotubular arrays can provide large surface
      areas for biological species attachment. In order to further enhance the
      biocompatibility of Ti medical implants, we deposited a pre-synthesized
      hydroxyapatite inside and on the nanotubular arrays, and examined the
      biocompatibility of the anodized TiO2 nanotubular arrays with pre-synthesized
      hydroxyapatite by in vitro assessment in simulated body fluid, and in vitro cell
      culture. The results showed that the hydroxyapatite coating was able to be
      induced on TiO2 nanotubular arrays with pre-synthesized hydroxyapatite within 5
      days while only a thin film composed of calcium phosphorous chemicals formed on
      as-formed TiO2 nanotubular arrays. The cell culture evaluation further proved the
      enhancement of cell attachment and proliferation on TiO2 nanotubular arrays with
      pre-synthesized hydroxyapatite as opposed to those without pre-synthesized
      hydroxyapatite. The present study proves that formation of TiO2 nanotubular
      arrays with pre-synthesized hydroxyapatite a promising method to enhance the
      biocompatibility of Ti implants.

PMID- 23882760
TI  - Preparation and characterization of silver-doped nanobioactive glass particles
      and their in vitro behaviour for biomedical applications.
AB  - In this study, silver-doped silica- and phosphate-based nanobioactive glass
      compositions (58SiO2-(33- x)CaO-9P2O5-xAg2O) (x = 0, 0.5, 1, 2 and 3 mol%) were
      synthesised by a simple and cost-effective sol-gel method. The prepared samples
      were characterised by X-ray diffraction, Fourier transform infrared spectroscopy,
      transmission electron microscopy, scanning electron microscopy and energy
      dispersive X-ray fluorescence spectrometer studies. All the compositions of the
      glass samples revealed amorphous phase with spherical morphology and a particle
      size less than 100 nm. The prepared glass samples reveal the specific surface
      area in the range of 55.31-90.69 m2 g(-1). The bioactivity of glass samples was
      confirmed through the formation of the hydroxyapatite layer on glass surfaces
      during in vitro studies in which silver doped glasses (2 and 3 mol%) showed
      better bioactivity. A better biocompatibility was achieved in human gastric
      adenocarcinoma cell line in case of silver-free glass sample while comparing the
      biological behaviour of Ag2O-doped glasses. Further, the Ag2O-doped nanobioactive
      glasses revealed significant antibacterial activity against Staphylococcus aureus
      and Escherichia coli. Ag2O substitutions showed better in vitro bioactivity and
      remained slightly toxic to human cells at a concentration of 100 microg mL(-1).
      Silver-doped nanobioactive glass shows good antimicrobial property as well as no
      significant toxic for implant applications.

PMID- 23882761
TI  - Grain growth associates mechanical properties in nano-hydroxyapatite bone
      scaffolds.
AB  - The sintering behaviors and resulting mechanical properties of nano
      hydroxyapatite (HAP) are studied with a self-developed selective laser sintering
      (SLS) system. All sintered specimens are fabricated in the sintering range of
      pure nano-HAP (laser energy densities in 1.6-4.0 J/mm2). The grain
      characteristics and mechanical properties are tested with scanning electron
      microscopy (SEM) and Vickers hardness tester respectively after the sintered
      specimens are polished with diamond paste and etched with 0.5% hydrofluoric acid
      (HF). The studies reveal improvements in the microstructural and mechanical
      properties of the sintered specimens with increasing laser energy density.
      However, abnormal grain growth severely decreases the mechanical properties when
      the laser energy density passes a certain critical point (3.4 J/mm2). The nano
      grain ceramic with the Vickers hardness value of 4.54 GPa is obtained at the
      critical point. It provides guidance to fabricate nano-grain bone scaffold with
      pure nano-HAP powder by SLS.

PMID- 23882763
TI  - Consecutive magnetic and magnetocaloric transitions in herringbone nanostructured
      Heusler Mn50Ni41Sn9 alloy.
AB  - A herringbone nanostructured Mn-rich Heusler Mn50Ni50-Sndelta (8 - 9) alloy
      exhibits tailored magnetocaloric properties in the martensite and ferro <->
      paramagnetic transitions concur in a narrow temperature window. In a Sn --> Ni
      substitution 8 - 9, the martensite (M) <-- austenite (A) transition up-lifts
      adequately well above the room temperature - 310.5 K in the DSC thermogram and
      magnetization scanned with temperature. A noninterrupted heating following a
      cooling in DSC at a given rate gives a smaller enthalpy change deltaH(M <-- A) -
      deltaH(M --> A approximately equal to 282 mJ/g (deltaC(P)(M <-- A) - deltaC(P)(M 
      -> A) approximately equal to 0.025 mJ/g-K in the heat capacity), i.e., the M <->
      A transition process lacks a complete reversibility. Warming a zero-field cooled
      sample retains lower magnetization (sigma) at low fields B, e.g., by 58% over the
      field cooled value at 5 mT, wherein merely low field magnetic susceptibility
      imparts the magnetization process. A reversible thermal hysteresis thus the
      transition traces in cooling and heating. The field diminishes difference in two
      sigma-values progressively, e.g., only - 12% lasts at 5 T. The two curves
      bifurcate below 160 K (B-5 mT) and the gap grows exponentially over lower
      temperatures before sigma(M <-- A) gets steady near 60 K in a superparamagnetic
      (SPM) behavior. The SPM feature (follows the Langevin model) below a paramagnetic
      regime begins (> or = 250 K) before a ferromagnetic A-state lines-up the
      successive transitions. Temperature and frequency dependence ac and dc
      susceptibilities describe the surface spins dynamics.

PMID- 23882762
TI  - Fabrication and characterization of gold nanoflowers formed via chitosan
      tripolyphosphate template films for biomedical applications.
AB  - Flowerlike gold nanostructure was facilely prepared by the seed-mediated growth
      of gold nanoparticles in chitosan-TPP template films. Firstly, chitosan
      nanoparticles, spontaneously formed by inter and/or intra cross-linking with TPP,
      were transformed into gel-type of chitosan-TPP films under strong sonication
      process. After then, gold seeds (1-3 nm) were entrapped in chitosan-TPP films via
      electrostatic interactions, and the resulting films were subsequently used as a
      template for growing gold nanoparticles and subsequent formation of anisotropic
      gold nanoflowers. The size and optical properties of gold nanoflowers were
      controlled simply by changing the ratio of gold salts to chitosan-TPP template
      films. Gold nanoflowers consisted of many aggregated nanodots exhibited broad
      Plasmon-derived absorption bands with strong red-shift into NIR wavelength, which
      might be a good prospect for SERS and biomedical applications.

PMID- 23882764
TI  - Scalability on roll-to-roll gravure printed dielectric layers for printed thin
      film transistors.
AB  - The manufacture of thin film transistors with reliable electrical properties, via
      full-printing on plastic foils, is a key step for the realization of costless and
      flexible electronics. To reach this goal, the dielectric layers should be smooth
      and free from failure while maintaining a high capacitance. In this paper, the
      parameters, affecting the film quality and capacitance of dielectric layers in a
      roll-to-roll gravure process, were investigated and some parameters were
      optimized.

PMID- 23882765
TI  - Sea urchin like shaped cdse nanoparticles grown in aqueous solutions via electron
      beam irradiation.
AB  - Cadmium selenide (CdSe) nanoparticles have been grown from an aqueous solutions
      containing equimolar ammoniated cadmium sulphate and sodium selenosulphate as
      precursors in presence of citric acid as a capping agent, via electron beam
      irradiation. The radiolytic processes occurring in the medium result in the
      formation of CdSe nanoparticles through the reactions mediated by hydrated
      electrons (e(aq)-). The dynamics of the formation of these nanoparticles was
      investigated by pulse radiolysis studies. The size of the primary nanoparticles
      as estimated from the absorption spectra recorded immediately was less than 3 nm.
      These nanoparticles exhibited strong excitonic absorption pattern and broad
      photoluminescence at room temperature, which has been attributed to the presence
      of surface states/defects. This has been confirmed by Raman spectral studies,
      where CdSe nanoparticles exhibited characteristic surface phonon modes at around
      250 cm(-1). The photoluminescence lifetime decay measurements further supported
      the existence of surface defects on the as-grown CdSe nanoparticles. These
      nanoparticles were found to exist in the agglomerated form of sea urchin like
      shapes of uniform size of about 500 nm as revealed from TEM and SEM images. These
      sea urchin like shaped CdSe nanoparticles grown in this route were found to be
      very stable under the ambient conditions. We infer that citric acid influences
      the growth as well as stability of these nanoparticles. It is expected that these
      nanomaterials could find potential applications in the field of sensors,
      catalysis and photovoltaics.

PMID- 23882766
TI  - Steered molecular dynamics simulations on the peeling and shearing of carbon
      nanotubes on a silicon substrate.
AB  - Steered molecular dynamics simulations were performed to investigate the peeling
      and shearing behavior of a single-walled carbon nanotube lying on a silicon
      substrate. Both the constant velocity and the constant force methods were applied
      to explore the adsorption of carbon nanotube and silicon substrate, and the
      efficiency of the two simulation methods was compared via a few representative
      examples. We examined the influences of the peeling angle, the shearing velocity,
      the initial distance between the carbon nanotube and the substrate, the
      connection point with the virtual ideal spring, the tube radius, as well as the 5
      7-7-5 and radius defect of the carbon nanotube. The numerical results coincide
      well with relevant experimental results. This work is helpful for the application
      of carbon nanotubes in silicon-based microelectronics.

PMID- 23882767
TI  - Stable silver/biopolymer hybrid plasmonic nanostructures for high performance
      surface enhanced Raman scattering (SERS).
AB  - Silver/biopolymer nanoparticles were prepared by adding 100 mg silver nitrate to
      2% polyvinyl alcohol solution and reduced the silver nitrate using 2% trisodium
      citrate for high performance Surface Enhanced Raman Scattering (SERS) substrates.
      Optical properties of nanoparticle were measured using UV/VIS spectroscopy and
      hyperspectral imaging microscopy. Nanoparticle morphology was analyzed using
      transmission electron microscopy. Substrate reproducibility and repeatability was
      checked by measuring SERS signals of trans-1,2-bis(4-pyridyl)ethylene (BPE) and
      Rhodamine 6G.

PMID- 23882768
TI  - Optical and magnetic studies of electrospun Mn-doped SnO2 hollow nanofiber dilute
      magnetic semiconductor.
AB  - The hollow nanofibers of Mn-doped SnO2 were fabricated by electrospinning method.
      The structural and magnetic properties of the electrospun fibers calcined at 600
      degrees C were studied. X-ray diffraction patterns of the nanofibers showed broad
      diffraction peaks and were indexed to the characteristic diffraction pattern of
      tetragonal SnO2. The hollow fiber micro-structure of Mn-doped and pure SnO2 were
      confirmed from the observed HRSEM and TEM analysis. Typical diameter of the
      hollow nanofibers was found to be around 150 nm. Strong emission peak in the
      visible region of the PL spectra characteristic of the optical activity of the
      SnO2 is obtained. Surface composition of the nanofiber and successful
      incorporation of Mn into SnO2 were confirmed from intense peaks recorded in the
      XPS spectra. Finally, a reasonable ferromagnetic transition observed at 10 K in
      the Mn-doped SnO2, substantiates that the presence of undetectable Sn-Mn solid
      solution or the formation of Mn based oxide secondary phases. It concludes that
      the induced ferromagnetism is only due to the precipitated impurity phases and
      does not arise from any intrinsic pure SnO2 or the dopant.

PMID- 23882769
TI  - Numerical study on electronic and optical properties of organic light emitting
      diodes.
AB  - In this paper, we present a finite element method (FEM) study of space charge
      effects in organic light emitting diodes. Our model includes a Gaussian density
      of states to account for the energetic disorder in organic semiconductors and the
      Fermi-Dirac statistics to account for the charge hopping process between
      uncorrelated sites. The physical model cover all the key physical processes in
      OLEDs, namely charge injection, transport and recombination, exciton diffusion,
      transfer and decay as well as light coupling, and thin-film-optics. The exciton
      model includes generation, diffusion, and energy transfer as well as
      annihilation. We assumed that the light emission originates from oscillating and
      thus embodied as excitons and embedded in a stack of multilayer. The out-coupled
      emission spectrum has been numerically calculated as a function of viewing angle,
      polarization, and dipole orientation. We discuss the accumulation of charges at
      internal interfaces and their signature in the transient response as well as the
      electric field distribution.

PMID- 23882770
TI  - Crown jewel-structured Au/Pd nanoclusters as novel catalysts for aerobic glucose
      oxidation.
AB  - Low-coordination Au sites have been proved to play a key role in defining the
      catalytic activity of Au nanoclusters (NCs). At the present time, it is still of
      great interest and challenge to design and synthesize catalysts containing the
      desired amount of low-coordinated Au atoms by a simple, easy, and large-scale
      method. In this study, PVP-protected 'crown jewel'-structured Au/Pd (CJ-Au/Pd)
      catalyst containing an abundance of top Au atoms were prepared by redox
      replacement reaction between Pd NCs and Au3+ ions. The catalytic activity of the
      CJ-Au/Pd NCs for aerobic glucose oxidation is about 3 times higher than that of
      the Au/Pd alloy NCs prepared by alcohol reduction method, although all of these
      NCs possess almost the same particle size.

PMID- 23882771
TI  - Ion-selective detection by plasticized poly(vinyl chloride) membrane in glass
      nanopipette with alternating voltage modulation.
AB  - An alternating current (AC) voltage modulation was applied to ion-selective
      observations with plasticized poly(vinyl chloride) membranes in glass
      nanopipettes. The liquid confronting the membranes in the nanopipettes, the
      conditioning process, and AC voltage modulation play important roles in the ion
      selective detection. In the AC detection system developed by us, where distilled
      water was used as the liquid within the nanopipettes, potassium ions were
      selectively detected in the sample solution of sodium and potassium ions because
      sodium ions were captured at the membrane containing bis(12-crown-4) ionophores,
      before the saturation of the ionophores. The membrane lost the selectivity after
      the saturation. On using sodium chloride as the liquid within the nanopipette,
      the membrane selectively detected potassium and sodium ions before and after the
      saturation of ionophores, respectively. The ion-selective detection of our system
      can be explained by the ion extraction-diffusion-dissolution mechanism through
      the bis(12-crown-4) ionophores with AC voltage modulation.

PMID- 23882772
TI  - Electron beam irradiated ITO films as highly transparent p-type electrodes for
      GaN-based LEDs.
AB  - We have investigated the effect of electron beam irradiation on the electrical
      and optical properties of ITO film prepared by magnetron sputtering method at
      room temperature. Electron beam irradiation to the ITO films resulted in a
      significant decrease in sheet resistance from 1.28 x 10(-3) omega cm to 2.55 x
      10(-4) omega cm and in a great increase in optical band gap from 3.72 eV to 4.16
      eV, followed by improved crystallization and high transparency of 97.1% at a
      wavelength of 485 nm. The overall change in electrical, optical and structural
      properties of ITO films is related to annealing effect and energy transfer of
      electron by electron beam irradiation. We also fabricated GaN-based light
      emitting diodes (LEDs) by using the ITO p-type electrode with/without electron
      beam irradiation. The results show that the LEDs having ITO p-electrode with
      electron beam irradiation produced higher output power due to the low absorption
      of light in the p-type electrode.

PMID- 23882773
TI  - Investigation on properties of electron-beam treated Mo back contact layer
      prepared by DC sputtering method.
AB  - Molybdenum (Mo) has been used as back contact layer in chalcopyrite solar cells
      family (CulnSe2 and its alloys) because it showed the excellence of electrical
      properties such as low resistivity at the Mo interference. Generally, there are
      strong corrleations between working pressure and properites such as adhesion and
      conductivity during deposition of Mo layer. Electrical properites might be
      inversely proportional to adehsion between Mo layer and glass substrate. Several
      methods have been executed for improvement of electrical properties and ahesion.
      In this study, DC sputtered Mo back contact layers on sodalime glass were
      prepared with working pressure range of 1-10 mTorr, and then all samples were
      treated by rounded exposure of electron beam at DC power of 3 kV for 5 minutes.
      After electron-beam treatement, all samples showed the lower resisitivity and
      sheet resisitance than as-deposited Mo layers. As working pressure decreased,
      grain size of e-beam treated samples gradually increased up to 30.7 nm. E-beam
      treated Mo layer might be a good candidate as back contact layer of tandem
      structured CIS families thin film solar cells.

PMID- 23882774
TI  - Spindle-like alpha-Fe2O3 embedded with TiO2 nanocrystalline: ion implantation
      preparation and enhanced magnetic properties.
AB  - Mastery of the structure of nanomaterials enables control of their properties to
      enhance their performance for a given application. A scalable method for
      synthesis of alpha-Fe2O3/TiO2 bi-component nanoparticles (NPs) with novel
      structure (TiO2 NPs filled into the a-Fe,203) by combining with wet-chemical
      route and ion implantation-based physical route has been proposed. Different
      implanted energy and the magnetic properties of bi-component a-Fe203/TiO2 NPs
      were investigated. The results illustrate alpha-Fe2O3/TiO2 composite NPs can be
      obtained by Ti ions implantation with different energy, and the saturation
      magnetization (M(s)) of the samples after ion implantation are significantly
      enhanced. The results also reveal that conversion phase from hematite to
      magnetite have been occurred under the thermal effects during ion implantation.

PMID- 23882775
TI  - Epoxy resin/carbon black composites below the percolation threshold.
AB  - A set of epoxy resin composites filled with 0.25-2.0 wt.% of commercially
      available ENSACO carbon black (CB) of high and low surface area (CBH and CBL
      respectively) has been produced. The results of broadband dielectric spectroscopy
      of manufactured CB/epoxy below the percolation threshold in broad temperature
      (200 K to 450 K) and frequency (20 Hz to 1 MHz) ranges are reported. The
      dielectric properties of composites below the percolation threshold are mostly
      determined by alpha relaxation in pure polymer matrix. The glass transition
      temperature for CB/epoxy decreases in comparison with neat epoxy resin due to the
      extra free volume at the polymer-filler interface. At room temperature, the
      dielectric permittivity is higher for epoxy loaded with CBH additives. In
      contrast, at high temperature, the electrical conductivity was found to be higher
      for composites with CBL embedded. The established influence of the CB surface
      area on the broadband dielectric characteristics can be exploited for the
      production of effective low-cost antistatic paints and coatings working at
      different temperatures.

PMID- 23882776
TI  - C-LFP-multi-walled carbon nanotubes composite cathode materials synthesized by
      solid-state reaction for lithium ion batteries.
AB  - Multi-walled carbon nanotubes (MWNT) was utilized as a conductive additive to
      enhance the capacity and rate capability of carbon coated LiFePO4 (C-LFP).
      Composites of C-LFP with MWNT (C-LFP-MWNT) were prepared by blending MWNT at
      different stages of C-LFP synthesis. The pre-blending (PrB) of MWNT (5, 10, 15
      wt%) with LFP precursor (PrB-C-LFP-MWNT) before calcination in a reducing
      environment (5 vol% H2 in N2) at 750 degrees C, produced phase pure crystalline
      LFP with a reduction in particle size as increase in MWNT content. This was
      contrasted with post-blending (PoB) of MWNT with as-synthesized C-LFP (PoB-C-LFP
      MWNT), which gave inferior electrochemical performances. The PrB-C-LFP-MWNT (10
      wt%) composite showed better cycle stability, higher rate capability, and faster
      Li diffusion characteristics than PoB-C-LFP-MWNT.

PMID- 23882777
TI  - Preparation of silver nanoparticles by a non-aqueous sol-gel process.
AB  - Using a non-aqueous sol-gel process with a direct calcination step in air after
      prior drying, silver nanoparticles with average size distribution ranging from 20
      to 100 nm were synthesised. Studies in reduced atmosphere were also performed
      with mixed results, both in phase and particle size, as the samples were found to
      be mixed with an amorphous phase. In oxidising atmosphere, the temperature and
      dwelling time were found to be critical factors with the former playing a larger
      role than the latter. Optimally nanoparticles of silver are best prepared by
      direct calcination in air of the precursor gel at 250 degrees C for 1 hour.
      Compared to silver particles prepared by microemulsions, the particle size is
      larger due to the thermal treatment, which causes a growth of the silver
      particles.

PMID- 23882778
TI  - Swift adsorptive removal of Congo red from aqueous solution by K1.33Mn8O16
      nanowires.
AB  - A swift and efficient approach to converting organic dye effluents into fresh
      water could be of substantial benefit. In this study, we presented facile
      hydrothermal synthesis of K1.33Mn8O16 nanowires in ammonium fluoride (NH4F)
      aqueous solution. The crystallization process of K1.33Mn8O16 nanowires was
      investigated. The as-obtained K1.33Mn8O16 nanowires were used for swift
      adsorptive removal of Congo red from aqueous solution without adjusting pH value
      at room temperature. Adsorption kinetic experimental data are well described by
      pseudo-second-order rate kinetic model, and the adsorption isotherm fits Langmuir
      isotherm model. The present investigation provides an efficient approach to
      designing and fabricating manganese-based nanomaterials for environmental
      remediation.

PMID- 23882779
TI  - Ultrastrong single-walled carbon nanotubes/ graphene oxide nanosheets hybrid
      network films as flexible electrode for energy storage.
AB  - Homogeneous free-standing SWCNT/GO hybrid network films were fabricated using
      vacuum filtration method and their performances to be used as flexible electrodes
      in electrochemical capacitors were studied. Firstly, the SWCNT/GO hybrid films
      were treated under different temperature to investigate the influence of oxygen
      containing groups on GO nanosheets on capacitive performance of them. Our results
      showed that the content of oxygen-containing groups had great influence on the
      capacitive performance of SWCNT/GO hybrid films and that the film annealed at 250
      degrees C under 5% H2/Ar flow displayed an optimal capacitive performance. For
      the film with SWCNT/GO mass ratio of 1:4, specific capacitances of 171.85, 162.9,
      148.98, 133.8, 112.8 and 82.24 F/g corresponding to discharge current of 5, 10,
      20, 40, 80 and 160 A/g, respectively, were achieved. Secondly, the influence of
      mass ratio of SWCNT/GO on capacitive performance of SWCNT/GO hybrid films was
      also demonstrated. The hybrid films exhibited extremely high mechanical strength
      with tensile strength up to 461 MPa and specific capacitance of 105.2 F/g at
      current density of 5 A/g in case of 1:1 mass ratio of SWCNT/GO. A higher specific
      capacitance of 206.7 F/s at discharge current of 5A/g was obtained for the films
      with SWCNT/GO mass ratio of 1:8. Our SWCNT/GO hybrid network films showed good
      flexibility and durability over 2000 bending cycles test, indicating the
      potential to be used in flexible energy-storage devices.

PMID- 23882780
TI  - Thermal oxidation of V2O3 nanocrystals: a template method for the fabrication of
      monoclinic phase VO2 nanocrystals.
AB  - We report the fabrication of VO2(M) nanocrystals by direct thermal oxidation V2O3
      nanocrystals. The controlling of the thermal oxidation temperature and vacuum is
      essential for obtaining pure VO2(M) nanocrystals. The VO2(M) nanocrystals have
      nearly a spherical morphology with sizes ranging from 50 to 80 nm and well
      dispersed. The phase transition temperature is about 65 degrees C with relatively
      narrow endothermic and exothermal peaks in DSC curve. Variable temperature
      resistance and infrared transmission measurements demonstrate a reversible phase
      transition of the VO2(M) nanocrystals. Our method is facile, economical and can
      be easily scaled-up for mass production.

PMID- 23882781
TI  - Fabrication of nanostructures on polyethylene terephthalate substrate by
      interference lithography and plasma etching.
AB  - We report results of an attempt to create nanostructures on polyethylene
      terephthalate substrate using the interference lithography and plasma etching
      technique. Methods to create nanogrooves, nanopillars, nanofins and nanoholes
      have been presented. The effects of chemical and physical etching associated with
      plasma etching on the synthesis of nanostructures were examined in detail.
      Different etch rates and anisotropy as a function of plasma power and pressure
      were reported and explained, offering good understanding of the physics of the
      etching process. Ways to improve anisotropy have been suggested and
      experimentally verified. We show that this method can produce nanostructured
      substrate with wide surface coverage and good uniformity. The flexibility of this
      method was demonstrated in that the period and shapes of the nanopattern can be
      varied easily without resorting to complicated fabrication processes and
      machinery. Our method brings forth an easy and cost-effective way to create
      uniform nanostructures on a large area in a controllable fashion.

PMID- 23882782
TI  - Volatile organic compound gas sensor based on aluminum-doped zinc oxide with
      nanoparticle.
AB  - Thick film semiconductor gas sensors based on aluminum-doped zinc oxide (AZO)
      with nanoparticle size were fabricated to detect volatile organic compound (VOC)
      existed in building, especially, formaldehyde (HCHO) gas which was known as the
      cause of sick building syndrome. The sensing materials for screen printing were
      prepared using roll milling process with binder. The crystallite sizes of
      prepared materials were about 15 nm through X-ray diffraction (XRD) analysis and
      scanning electron microscopy (SEM). Gas response characteristics were examined
      for formaldehyde (HCHO), benzene, carbon monoxide, carbon dioxide gas existing in
      building. In particular, the sensors showed responses to HCHO gas at sub ppm as a
      function of operating temperatures and gas concentrations. Also, we investigated
      sensitivity, repeativity, selectivity, and response time of sensor. The
      transients were very sharp, taking less than 2 s for 90% response. The sensor has
      shown very stable response at 350 degrees C and followed a very good behavior and
      showed 60% response in 50 ppb HCHO concentration at 350 degrees C operating
      temperatures.

PMID- 23882784
TI  - Effect of TiO2 nanoparticles on the hydrogen sorption characteristics of
      magnesium hydride.
AB  - The present paper explores the enhancement in hydrogen sorption behavior of MgH2
      with TiO2 nanoparticles. The catalytic effect of TiO2 nanoparticles with
      different sizes (7, 25, 50, 100 and 250 nm) were used for improving the sorption
      characteristics of MgH2. The MgH2 catalyzed with 50 nm of TiO2 exhibited the
      optimum catalytic effect for hydrogen sorption behavior. The desorption
      temperature of MgH2 catalyzed through 50 nm TiO2 was found to be 310 degrees C.
      This is 80 degrees C lower as compared to MgH2 having a desorption temperature of
      390 degrees C. It was noticed that the dehydrogenated MgH2 catalyzed with 50 nm
      TiO2 reabsorbed 5.1 wt% of H2 within 6 minutes at temperature and pressure of 250
      degrees C and 50 atm, respectively. The 50 nm TiO2 catalyst lowered the
      absorption activation energy of MgH2 from - 92 to - 52.7 kJ mol(-1).

PMID- 23882785
TI  - Graphene-enhanced environmentally-benign cutting fluids for high-performance
      micro-machining applications.
AB  - A canola-based cutting oil enhanced with graphene platelet (GPL) additives has
      been developed to fulfill the need for environmentally benign cutting oils for
      high performance micro-machining applications. Carboxyl-functionalized graphene
      platelets are used to enable stable GPL dispersion in the polar oil. Three oil
      formulations consisting of 0.05%, 0.10% and 0.15% GPL by weight are tested. The
      GPL-laden canola oil is first characterized based on its kinematic viscosity,
      thermal conductivity and coefficient of friction. Micro-turning tests are then
      performed to study the effect of GPL loading on the cutting temperature, cutting
      force, and the surface finish of the part. All tested loadings improve the
      cooling and lubricating properties of the canola oil. For cooling, this
      improvement is seen to increase with GPL loading. In the case of lubrication,
      there appears to be an optimal loading of around 0.10%. The presence of GPL also
      leads to a decrease in the surface roughness of the micro-machined surface but
      this improvement drops with increased GPL loading.

PMID- 23882783
TI  - Building nanoSPR biosensor systems based on gold magnetic composite
      nanoparticles.
AB  - Composite Fe3O4/Au nanoparticles are attracting considerable interest in
      developing visual and specific detection of biomolecular due to their unique
      physical and chemical properties. Here, two localize surface plasmon resonance
      (LSPR) probes based on Fe3O4/Au nanoparticles (nanoSPR biosensors) were
      fabricated by exploring 11-mercaptoundecanoic acid (MUA) and poly acrylic acid
      (PAA) as surface modification agents and subsequently conjugating rabbit IgG with
      the modified particles' surface. Comparative investigations showed the
      differences between MUA-particles and PAA-particles, as well as sensitivity of
      the two as-prepared nanoSPR biosensors when used in target goat anti-rabbit IgG
      colorimetric detection. Particles coated with PAA were in a better dispersion and
      showed an ionic independent stability, indicating PAA-particles have a potential
      application in colorimetric detection. In contrast, the MUA-particle probes
      revealed a higher sensitivity in SPR detection (50 nmol/L), and further kinetic
      studies showed the reactions between probes and target followed the second order
      and the reaction rate of MUA-probes was twice the rate of PAA-probes at the same
      temperature and condition. Such proof-of concept works reported here demonstrated
      that the protocol to build nanoSPR biosensors was favored in developing molecular
      probes, and the novel composite nanoparticles might serve as ideal probes for
      sensitive, selective and real time detection.

PMID- 23882786
TI  - Hydrothermal synthesis, characterization and luminescence properties of
      YbVO4:Ln3+ (Ln3+ = Er3+, Tm3+, Ho3+) nanocrystals.
AB  - Ytterbium orthovanadate YbVO4 nanocrystals with uniform size and shape were
      successfully synthesized through a facile hydrothermal approach using sodium
      tartrate (Na2tar) as the chelating ligand. X-ray diffraction (XRD), energy
      dispersive X-ray spectrum (EDX), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), high-resolution transmission electron microscopy
      (HRTEM), selected area electron diffraction (SAED) and photoluminescence (PL)
      spectra were taken to characterize the phases, morphologies, sizes, and
      luminescence properties of the samples. The results indicate that the YbVO4
      samples can be rationally modified in size and morphology by altering the Na2tar
      content, pH value and reaction time. The possible formation mechanism of the
      YbVO4 samples is proposed on the basis of time-dependent experiments.
      Additionally, the UC luminescence properties and the emission mechanisms of
      YbVO4:Ln3+ (Ln3+ = Er3+, Tm3+, Ho3+) samples were systematically investigated,
      which show green (Er3+, 4S(3/2), 2H(11/2) --> 4I(15/2)), blue (Tm3+, 1G(4) -->
      3H(6)) and green (Ho3+, 5S(2) --> 5I(8)) luminescence under 980 nm NIR
      excitation, respectively. These merits of multicolor emissions in the visible
      region endow this kind of material with potential applications in the field of
      light display systems, lasers, and optoelectronic devices.

PMID- 23882787
TI  - Real-time pulse measurement of nano-scale field effect transistors: cancellation
      of displacement current and extraction of coupling capacitance.
AB  - Real-time pulse measurements of nano-scale field effect transistors (FETs) are
      reported. We demonstrate the direct monitoring of the real-time current of bottom
      up assembled silicon nanowire FET and top-down fabricated gate-all-around silicon
      nanowire FET, both with the diameter of approximately 50 nm. We demonstrate that
      the displacement current can be cancelled out from the measured pulse responses.
      On the other hand, the displacement current also can be utilized to obtain the
      coupling capacitance between the gate and source of the FETs.

PMID- 23882788
TI  - Influence of W-doping on electrochemical performance of spinel LiMn2O4.
AB  - The structural and electrochemical properties of W-doped LiMn2O4 and
      LiAl0.025Mn1.975O4 have been investigated to determine the role of W. The
      cathodic materials were synthesized by sol-gel method, using citric acid as the
      chelating agent. The results revealed that the substitution of W affects the
      lattice dimension, the morphology, and the electrochemical performance.
      Substitution of Al induces an obvious decrease in the electrochemical capacity
      (but higher capacity retention) and in the case of W the decrease was drastic. As
      observed from XRD, only a fraction of W is included in the spinel structure.
      However, for the LiAl0.025W0.025Mn1.95O4, a compromised value is reached between
      the Al-doped and W-doped LiMn2O4 in terms of capacity and cyclic performance. The
      pristine spinel LiMn2O4 synthesized by this method shows a relatively superior
      electrochemical performance at high C-rate with excellent capacity retention.

PMID- 23882789
TI  - Quaternized poly(styrene ethylene butylene poly styrene)/multiwalled carbon
      nanotube composites for alkaline fuel cell applications.
AB  - The present study is aimed at synthesizing a novel anion exchange composite
      membrane from quaternized polystyrene-block-poly(ethylene-ran-butylene)-block
      polystyrene [QPSEBS] and functionalized multi walled carbon nanotubes (f-MWCNT)
      by solution casting method. The characteristic properties of the QPSEBS/f-MWCNT
      composite membranes were investigated using Fourier transform infrared (FTIR), UV
      Visible spectroscopy, thermo-gravimetric analysis (TGA), scanning electron
      microscopy (SEM), X-ray diffraction (XRD) studies and Raman spectroscopy. The
      water uptake, ion exchange capacity, ionic conductivity, methanol permeability
      and selectivity ratio of the membranes were also studied. The prepared composite
      membranes were tested in an in-house fabricated alkaline membrane fuel cell
      (AMFC) set up using Pt/C as the common anode catalyst and three different cathode
      catalysts namely Pt/C, Pd-Ni/C and Ag/C. Among all the three cathode catalysts,
      Pt/C for QPSEBS/5% f-MWCNT is found to show the maximum power density and open
      circuit voltage (OCV) of 187 mW cm(-2) and 0.73 V respectively. For direct
      methanol alkaline membrane fuel cells (DMAMFC), the OCV of QPSEBS/5% f-MWCNT is
      found to be 0.76 V and the maximum power density of 59.5 mW cm(-2) is achieved at
      a current density of 175 mA cm(-2).

PMID- 23882790
TI  - Antireflective coatings on Fresnel lenses by spin-coating of solid silica
      nanoparticles.
AB  - Antireflective (AR) coatings were fabricated from solid silica nanoparticles
      (SNPs) of ca. 16 nm in size on Fresnel lenses via one-step spin coating without
      any high temperature treatment. Transmission electron microscopy was used to
      observe the morphology and structure of the SNPs. Transmission spectra were
      recorded on a UV-vis-NIR spectrophotometer. The results indicated that Fresnel
      lenses covered with the SNPs coatings were much more transparent than the
      uncoated Fresnel lens. The maximum transmittance of the coated Fresnel lenses
      reached as high as 99.8%, whereas that of the uncoated Fresnel lens is only
      94.3%. Surface wettability was studied by a contact angle/interface system, and
      the results indicated that the coatings on Fresnel lenses were more hydrophilic
      than the uncoated Fresnel lens. The surface morphologies and structures of the
      coatings were examined by scanning electron microscopy (SEM) and atomic force
      microscopy (AFM). The mechanical robustness of the coatings was examined by
      pencil scratch tests and attenuated total reflection infrared spectroscopy (ATR
      IR).

PMID- 23882791
TI  - Properties of individually addressable ferroelectric nanocapacitor arrays
      fabricated by focused ion beam milling.
AB  - Well-ordered large-areas individual addressable ferroelectric nanocapacitor
      arrays with Pt top electrode and various lateral sizes down to below 100 nm have
      been fabricated by focused ion beam (FIB) milling on Nb-doped single-crystal
      SrTiO3(001) substrate. The well-shaped "butterfly" displacement-voltage loop is
      indicative of strong ferroelectricity of the nanocapacitor arrays. All cells in
      the arrays with a top to bottom polarization in the initial milled state. The as
      grown state domain images with various contrasts illustrate that the cells have
      different domain structure. The dispersion of properties and size effects exist
      jointly in the arrays. The piezoresponse of same cell size are different, and the
      difference increases with increasing cell size. The piezoresponse properties of
      some individual cell don't exhibit size dependence, but the properties of all
      cells have an obvious size depended tendency that the piezoresponse values
      decreases statistically with decreasing cell size. The size effects were
      dominated by the ion damage owing to high damaged-layer-to-volume ratio in the
      smaller cells, while the dispersion of properties was dominated by the
      inhomogeneous texture and various domain structures of the cells.

PMID- 23882792
TI  - Current enhancement of aluminum doped ZnO/n-Si isotype heterojunction solar cells
      by embedding silver nanoparticles.
AB  - To improve Plasmonic energy harvesting, the Al doped ZnO (AZO) and Si
      heterojunction was studied for plasmonic photovoltaic applications. Silver
      nanoparticles (Ag NPs) were embedded in AZO, resulting in direct energy absoption
      from Ag NPs, positioned close to the junction. This structure has a benefit of
      avoiding highly doped lossy layers of conventional solar cell structures. Al
      doped ZnO (AZO) was deposited on n-Si substrate by dual beam sputtering method to
      fabricate AZO/Si heterojunction solar cells. AZO provides a transparent current
      spreading effect and rectifying junction with n type silicon (Si). Silver
      nanoparticles (Ag NPs) were embedded in AZO film (240-270 nm thick) with a
      sandwich-like structure. The position of Ag NPs in the AZO film was controlled to
      be located at 10, 20 and 40 nm distance from the Si absorber layer. Fabricated
      solar cells show improved performance in terms of the short circuit current
      (J(sc)) and the quantum efficiency (QE). Finite difference time domain (FDTD)
      simulations were carried out to investigate the QE enhancement and optimize
      photocurrent gain under an AM1.5G solar spectrum. In calculation, absorption
      enhancement is maximized when Ag NPs are located close to the Si layer in the
      range of 10-40 nm. Experimentally, 20 nm distance of Ag NPs from the Si showed
      the best performance with 0.36 V of open circuit voltage (V(oc)), 28.3 mA/cm2 of
      J(sc) and 5.91% of coversion efficiency. The QE showed 15% of enhancement around
      lambda = 435 nm and 5-10% of enhancement within lambda = 600-1000 nm.

PMID- 23882793
TI  - Photoluminescence properties of NaSr(P, V)O4:Eu3+ phosphors.
AB  - Eu3+ activated NaSr(P,V)O4 phosphors have been synthesized using solid state
      reaction method and further characterized for their structure and optical
      properties using different techniques such as X-ray diffraction, scanning
      electron microscopy, photolumniscenec excitation, emission, and chromaticity
      coorrdinate analysis, etc. Material shows a broad excitation peak (monitored for
      lambda(ems) = 613 nm) lying in the 300-360 nm region and gives intense
      transitions (lambda(exc) = 320 nm) namely 5D0 --> 7F1 at 590 nm, 5D0 --> 7F2 at
      613 nm, 5D0 --> 7F3 at 650 nm, and 5D0 --> 7F4 at 700 nm due to Eu3+ ion. Our
      results show that replacement of the PO4(3-) ions with isomorphic VO4(3-) ions
      improves the structural stability and the overall intensity of the emission. The
      maxium emission intensity is achieved for the NaSr(P0.4, V0.6)O4:Eu3+ phosphor.
      An estimated increase of an order is attained for the NaSr(P0.4, V0.6)O4:Eu3+
      phosphor as compared to NaSrPO4:Eu3+ or NaSrVO4:Eu3+ phosphor. The chromaticity
      coordinate of the phosphor (0.68, 0.31) lies well within the red region and
      suggest that the material could be an alternative red phosphor for lighting and
      display applications.

PMID- 23882794
TI  - Structural and optical characterization of Eu3+ doped beta-Ga2O3 nanoparticles
      using a liquid-phase precursor method.
AB  - Eu3+ doped beta-Ga2O3 and non-doped beta-Ga2O3 nanoparticles were synthesized at
      800 degrees C using a liquid-phase precursor (LPP) method, with different
      annealing times and Eu3+ ion concentrations. Eu3+ doped beta-Ga2O3 nanoparticles
      showed broad XRD peaks, revealing a second phase compared with the non-doped beta
      Ga2O3 nanoparticles. The cathode luminescence (CL) spectra of beta-Ga2O3 and Eu3+
      doped beta-Ga2O3 nanoparticles showed a broad band emission (300-500 nm) of
      imperfection and two component emissions. The luminescence quenching properties
      of Eu3+ dopant ion concentration appeared gradually beyond 5 mol% in our
      investigation.

PMID- 23882796
TI  - Preparation of TiO2/SiO(x) double-layer films on glass beads and its application
      to NO and SO2 removal.
AB  - Glass beads were coated with SiO(x) thin film as the first layer and with TiO2
      thin film as the second layer by a rotating cylindrical PCVD reactor. The
      thicknesses of TiO2/SiO(x) double-layer films were measured by scanning electron
      microscopy. Glass beads coated with TiO2/SiO(x) double-layer films were packed
      inside the cylindrical reactor. NO and SO2 removal by dielectric barrier
      discharge-photocatalyst (DBD-P) hybrid process was tested for various conditions
      of process variables. The NO and SO2 removal efficiencies were improved by using
      a combination of dielectric barrier discharge and photodegradation by TiO2/SiO(x)
      double-layer films. The stronger the applied voltage is, the higher the pulse
      frequency is, or the longer the gas residence time is, the higher the NO and SO2
      removal efficiencies become. In this study, we found that the glass beads coated
      with TiO2/SiO(x) double-layer films by a rotating cylindrical PCVD reactor could
      be used effectively to remove NO and SO2 by DBD-P hybrid process.

PMID- 23882795
TI  - Physiological effects of magnetic iron oxide nanoparticles towards watermelon.
AB  - Nanoparticles (NPs) have been exploited in a diverse range of products in the
      past decade or so. However, the biosafety/environmental impact or legislation
      pertaining to this newly created, highly functional composites containing NPs
      (otherwise called nanomaterials) is generally lagging behind their technological
      innovation. To advance the agenda in this area, our current primary interest is
      focused on using crops as model systems as they have very close relationship with
      us. Thus, the objective of the present study was to evaluate the biological
      effects of magnetic iron oxide nanoparticles towards watermelon seedlings. We
      have systematically studied the physiological effects of Fe2O3 nanoparticles
      (nano-Fe2O3) on watermelon, and present the first evidence that a significant
      amount of Fe2O3 nanoparticles suspended in a liquid medium can be taken up by
      watermelon plants and translocated throughout the plant tissues. Changes in
      important physiological indicators, such as root activity, activity of catalase
      (CAT), peroxidase (POD) and superoxide dismutase (SOD), chlorophyll and
      malondialdehyde (MDA) contents, ferric reductase activity, root apoplastic iron
      content were clearly presented. Different concentrations of nano-Fe2O3 all
      increased seed germination, seedling growth, and enhanced physiological function
      to some degree; and the positive effects increased quickly and then slowed with
      an increase in the treatment concentrations. Changes in CAT, SOD and POD
      activities due to nano-Fe2O3 were significantly larger than that of the control.
      The 20 mg/L treatment had the most obvious effect on the increase of root
      activity. Ferric reductase activity, root apoplastic iron content, and watermelon
      biomass were significantly affected by exposure to nano-Fe2O3. Results of
      statistical analysis showed that there were significant differences in all the
      above indexes between the treatment at optimal concentration and the control.
      This proved that the proper concentration of nano-Fe2O3 could not only increase
      seed germination and seedling growth, but also ultimately improve physiological
      function and resistance to environmental stresses of watermelon.

PMID- 23882797
TI  - Structural characterization of rotavirus-directed synthesis and assembly of
      metallic nanoparticle arrays.
AB  - Self-assembled structures derived of viral proteins display sophisticated
      structures that are difficult to obtain with even advanced synthesis methods and
      the use of protein nanotubes for synthesis and organization of inorganic
      nanoarrays into well-defined architectures are here reported. Nanoparticle arrays
      derived of rotavirus VP6 nanotubes were synthesized by in situ functionalization
      with silver and gold nanoparticles. The size and morphology of metal
      nanoparticles were characterized by transmission electron microscopy (TEM) and
      high resolution TEM (HR-TEM). Processing of micrographs to obtain fast Fourier
      transforms (FFT) patterns of nanoparticles shown that the preferred morphologies
      are fcc-like and multiple twinned ones. Micrographs were used to assign structure
      and orientation, and the elemental composition analysis was performed with energy
      dispersive spectroscopy (EDS). Structural characterization of functionalized
      rotavirus VP6 demonstrated its utility for directed construction of hybrid
      anisotropic nanomaterials formed by arrays of metallic nanoparticles.

PMID- 23882798
TI  - Effect of post-annealing treatment on photocatalytic and photoelectrocatalytic
      performances of TiO2 nanotube arrays photoelectrode.
AB  - Highly ordered TiO2 nano-tube arrays (TNTAs) photoelectrodes were prepared
      through anodization method, followed by annealing treatment. Morphologies and
      structures of the as-prepared TNTAs samples were investigated through scanning
      electron microscopy (SEM) and X-ray diffraction (XRD). In addition, the optical
      and photoelectrochemical (PECH) properties were investigated through ultraviolet
      visible diffuse reflectance spectroscopy (UV-vis DRS) and transient photocurrent
      response. Furthermore, the photodecomposition performances were investigated
      through the yield of hydroxyl (*OH) radicals and photocatalytic (PC) degradation
      of RhB under Xenon light irradiation. Results indicated that the TNTAs samples
      annealed at 723 K exhibited the highest photocurrent response, PC performance and
      yield of *OH radicals, in which 60.8% of RhB could be degraded by PC degradation
      within 60 min. The high PC performance could mainly be attributed to the anatase
      structure, high crystallinity and highly ordered nano-tubular structure, which
      favored the transfer and separation of photoinduced charge carriers. This study
      suggests that highly ordered nano-structure could provide superior pathway for
      the charge transfer and separation.

PMID- 23882799
TI  - Fabrication of SiC nanoparticles by physical milling for ink-jet printing.
AB  - Here we tried to show the possibility of mechanical milling method for
      fabrication of SiC nanoparticles and ink-jet printing method to make SiC patterns
      for use as several applications, e.g., micro hotplates. Planetary milling was
      employed to fabricate the nano-scale SiC particles from coarse powders. After 100
      hours of milling, the size of the SiC particles decreased to about 100 nm, which
      was sufficient for the formulation of ink for ink-jet printing. The SiC particles
      were dispersed in an ink system consisted of ethylene glycol and ethanol with a
      small amount of additives. The ink with SiC nanoparticles could be successfully
      printed on an alumina substrate by the ink-jet printing method.

PMID- 23882800
TI  - Connecting carbon nanotubes using Sn.
AB  - Process of Sn coating on mutiwalled carbon nanotubes (MWCNT) and formation of
      interconnections among nanotubes are studied using high resolution transmission
      electron microscopy (HRTEM) and energy dispersive X-ray spectroscopy (EDX).
      Surface oxidation of nanotubes during heating with HNO3 prior to the SnCl2
      treatment and the bonding between functional groups and Sn are found to be
      responsible for the coating and its stability. Open nanotubes are filled as well
      as coated during tin chloride treatment. Coating and filling are converted into
      the coatings on the inner as well as outer walls of the nanotubes during
      reduction with H2/N2. EDX studies show the formation of intermetallic compounds
      e.g., Cu6Sn5 and Cu3Sn at the joints between nanotubes. Formation of
      intermetallic compounds is supposed to be responsible for providing the required
      strength for bending and twisting of nanotubes joining of nanotubes. Paper
      presents a detailed mechanism of coating and filling processes, and
      interconnections among nanotubes.

PMID- 23882801
TI  - Photocatalytic activity of TiO2 nanotubes doped with Ag nanoparticles.
AB  - TiO2 nanotubes formed on the surface of commercially pure titanium were prepared
      by anodizing processing and were then heat-treated. The silver doping was
      processed with different molar concentration of AgNO3 aqueous solution. The
      silver-doped TiO2 nanotubes were characterized using field emission scanning
      electron microscopy, ultraviolet visible near-infrared spectrophotometer and
      ampere-volts (I-V) curve system. The 20-100 nm Ag nanoparticles were well doped
      atop, inside, and between the nanotubes. The I-V curve of the TiO2 nanotubes
      increased with heat treatment temperature. The silver-doped TiO2 nanotubes with
      anatase plus rutile phases had better photocatalytic activity.

PMID- 23882802
TI  - Effect on electron beam treatment of radio frequency sputtered i-ZnO thin films
      for solar cell applications.
AB  - Intrinsic ZnO (i-ZnO) thin films were prepared using radio frequency (RF)
      sputtering method with working pressure range of 1-20 mTorr and treated by
      electron beam (e-beam) irradiation unit with 300 W of RF power and 2.5 kV of DC
      power for 5 min. As working pressure increased to 20 mTorr, deposition rate of
      samples gradually decreased from 0.3 angstroms/sec to 0.18 angstroms/sec and
      grain size from 23.6 nm to 16.0 nm. After e-beam treatment on RF sputtered i-ZnO
      thin films with increasing of working pressure, thickness were totally declined
      by 10% and grain sizes were grown bigger. The electrical properties of e-beam
      treated samples were remarkably improved to be - 10(18) cm(-3) of carrier
      concentration, 2-7 cm2/Vs of Hall mobility and - 10(-1) omega x cm of
      resistivity. Transmittance of e-beam treated samples were up to -90% and optical
      bandgap increased to 3.27-3.31 eV, resulted from decline of thickness. The better
      properties of ZnO thin films as a buffer layer in thin film solar cells could be
      obtained by e-beam treatment method.

PMID- 23882803
TI  - Thin film rechargeable electrodes based on conductive blends of nanostructured
      olivine LiFePO4 and sucrose derived nanocarbons for lithium ion batteries.
AB  - The present study provides the first reports of a novel approach of
      electrophoretic co-deposition technique by which titanium foils are coated with
      LiFePO4-carbon nanocomposites synthesized by sol gel route and processed into
      high-surface area cathodes for lithium ion batteries. The study elucidates how
      sucrose additions as carbon source can affect the surface morphology and the
      redox reaction behaviors underlying these cathodes and thereby enhance the
      battery performance. The phase and morphological analysis were done using XRD and
      XPS where the LiFePO4 formed was confirmed to be a high purity orthorhombic
      system. From the analysis of the relevant electrochemical parameters using cyclic
      voltammetry and electrochemical impedance spectroscopy, a 20% increment and 90%
      decrement in capacity and impedance values were observed respectively. The
      composite electrodes also exhibited a specific capacity of 130 mA h/g. It has
      been shown that cathodes based on such composite systems can allow significant
      room for improvement in the cycling performance at the electrode/electrolyte
      interface.

PMID- 23882804
TI  - Variation of microstructural and optical properties in SILAR grown ZnO thin films
      by thermal treatment.
AB  - The influence of thermal treatment on the structural and morphological properties
      of the ZnO films deposited by double dip Successive ionic layer by adsorption
      reaction is presented. The effect of annealing temperature and time in air
      ambient is presented in detail. The deposited films were annealed from 200 to 400
      degrees C in air and the structural properties were determined as a function of
      annealing temperature by XRD. The studies revealed that films were exhibiting
      preferential orientation along (002) plane. The other structural parameters like
      the crystallite size (D), micro strain (epsilon), dislocation density (delta) and
      stacking fault (alpha) of as-deposited and annealed ZnO films were evaluated and
      reported. The optical properties were also studied and the band gap of the ZnO
      thins films varied from 3.27 to 3.04 eV with the annealing temperature. SEM
      studies revealed that the hexagonal shaped grains with uniformly distributed
      morphology in annealed ZnO thin films. It has been envisaged using EDX analysis
      that the near stoichiometric composition of the film can be attained by thermal
      treatment during which microstructural changes do occur.

PMID- 23882805
TI  - Roll to plate printed stretchable silver electrode using single walled carbon
      nanotube on elastomeric substrate.
AB  - Stretchable electronics may open new applications in display, sensors and
      actuators. To attain the stretchable electronics, the ink formulation should be
      compatible with elastomeric substrates. Here, we present the formulation of
      silver nanoparticles and single walled carbon nanotubes (SWNTs) for printing
      stretchable silver electrodes on the elastomeric substrates. Highly conductive
      stretchable electrodes can be printed directly on the poly(styrene-b-butadiene-b
      styrene) (PSBS) substrates by roll to plate (R2P) gravure printer. During the
      stretching test, R2P printed silver based stretchable electrodes show the high
      conductivity of 1000 S cm(-1) at 0.27 wt% of SWNT loading. Furthermore, the
      resistance of the printed silver electrode was not changed up to 15% of tensile
      strain.

PMID- 23882806
TI  - Preparation, characterization of C/Fe-Bi2WO6 nanosheet composite and degradation
      application of norfloxacin in water.
AB  - A novel C/Fe-Bi2WO6 nanosheet composite photocatalyst combining the properties of
      both semiconductor and Fenton like catalyst was prepared via a two-step method
      involving Resin carbonization and hydrothermal process. The samples were
      characterized by X-ray diffraction (XRD), scanning electronic microscopy (SEM)
      and energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM),
      UV-vis diffuse reflectance spectra (DRS), X-ray photoelectron spectroscopy (XPS),
      Fourier transformed infrared spectroscopy (FT-IR) and nitrogen adsorption
      desorption measurements. Structure analyses indicated that C/Fe-Bi2WO6 presented
      a nanosheet and macro-meso dual porosity structure. The as-prepared composite
      exhibited high efficiency in the photocatalytic decomposition of norfloxacin
      (NOR) by the assistance of H2O2. This method is promising due to its inexpensive
      starting materials and good photocatalyst for degradation of emerging
      micropollutants.

PMID- 23882807
TI  - Effect of carbon nanotube addition on the wear behavior of basalt/epoxy woven
      composites.
AB  - The effect of acid-treated carbon nanotube (CNT) addition on the wear and dynamic
      mechanical thermal properties of basalt/epoxy woven composites was investigated
      in this study. Basalt/CNT/epoxy composites were fabricated by impregnating woven
      basalt fibers into epoxy resin mixed with 1 wt% CNTs which were acid-treated.
      Wear and DMA (dynamic mechanical analyzer) tests were performed on basalt/epoxy
      composites and basalt/CNT/epoxy composites. The results showed that the addition
      of the acid-treated CNTs improved the wear properties of basalt/epoxy woven
      composites. Specifically, the friction coefficient of the basalt/epoxy composite
      was stabilized in the range of 0.5-0.6 while it fell in the range of 0.3-0.4 for
      basalt/CNT/epoxy composites. The wear volume loss of the basalt/CNT/epoxy
      composites was approximately 68% lower than that of the basalt/epoxy composites.
      The results also showed that the glass transition temperature of basalt/CNT/epoxy
      composites was higher than that of basalt/epoxy composites. The improvement of
      wear properties of basalt/epoxy composites by the addition of acid-treated CNTs
      was caused by the homogeneous load transfer between basalt fibers and epoxy
      matrix due to the reinforcement of CNTs.

PMID- 23882808
TI  - Enhancement in the microstructure and photoluminescence properties of YVO4:Eu3+
      by Al doping.
AB  - Al contents have been doped as a sensitizer to improve the luminescent
      brightness, and the conventional solid state reaction method has been used to
      synthesize the phosphors. Al doping effects on the microstructures of YVO4:Eu3+
      phosphors were measured by X-ray diffraction (XRD) and field emission scanning
      electron microscopy (FESEM). The luminescent characteristics were characterized
      by photoluminescence excitation (PLE) and emission (PL) measurements.
      Incorporation of Al3+ ions into the YVO4:Eu phosphors has greatly enhanced the
      crystallinity, particle size and hence the luminescence properties and the
      optimum concentration in Al dopants are found to be 0.05 mol. The
      photoluminescence intensity of 0.05 mol Al(3+)-doped YVO4:Eu3+ phosphors was
      improved by a factor of 1.41, in comparison with undoped Y0.95Eu0.05VO4 phosphor.
      The improvement in photoluminescence properties with Al doping may result from
      the improved crystallinity and from the enlarged grain sizes inducing lower
      scattering loss.

PMID- 23882809
TI  - Optoelectronic properties of CdSe0.75S0.25 nanocrystals assembled into micro
      electrodes.
AB  - CdSe0.75S0.25 semiconductor nanocrystals were synthesized by chemical colloidal
      route. The crystal structure, morphology and optical properties of synthesized
      CdSe0.75S0.25 nanocrystals were characterized by XRD, TEM and UV-Vis absorption
      spectroscopy respectively. The crystal structure of CdSe0.75S0.25 is face
      centered Cubic sphalerite phase. The average size is about 7 nm in diameter. A
      gold tip-to-tip structure electrode with the gap size -20 microm was fabricated
      using conventional optical lithography technique followed by film deposition and
      standard lift-off process. An optoelectronics device was fabricated based on
      CdSe0.75S0.25 by assembling nanocrystals into electrodes by using
      dielectrophoresis (DEP) process. The electrical transport properties and opto
      electrical transport properties of the fabricated device were measured at
      temperature range from 5 K to 305 K. The results show that the resistance of
      CdSe0.75S0.25 NCs increases with the temperature decreases, indicating a typical
      semiconductor behavior. An obvious photoconductive behavior was observed,
      demonstrated potential application in nano-optoelectronics devices. After data
      analyzing, the conductivity shows the 0.5 exponent of Efros-Shklovskii variable
      range-hopping (ES-VRH) model.

PMID- 23882810
TI  - Boric oxide deposition on carbon nanofibers for oxidation resistance.
AB  - The boric oxide deposition was performed to improve the oxidation resistivity of
      carbon nanofiber (CNF) from electrospinning at elevated temperatures. The
      stabilized electrospun polyacrylonitrile (PAN) nanofibers were coated with boric
      oxide, followed by heat treatment up to 1000, 1200, and 1400 degrees C in an
      inert nitrogen atmosphere. The relative oxidation resistance of boric oxide
      coated CNFs showed oxidation resistive property, which was determined by weight
      loss after running a thermogravimetric analyzer (TGA) under air flow. The data
      were used for the calculations of activation energies through Arrhenius plot. The
      oxidation resistance of the boric oxide-coated CNFs was depended on the heat
      treatment temperature, the higher the temperature more resistive to oxidation.
      The boric oxide-coated CNFs showed extended oxidation resistivity as remaining 40
      83% (w) of the original weight at the high temperature 1000 degrees C under air.

PMID- 23882811
TI  - Robust fabrication method for silicon nanowire field effect transistors for
      sensing applications.
AB  - This paper demonstrates a new method for the top-down production of silicon
      nanowire field effect transistors for sensing applications. A simple and robust
      method for the fabrication of these devices is described, using only conventional
      CMOS (Complementary Metal Oxide Semiconductor) processing techniques making it
      manufacturable on large scale in a broad range of production facilities.
      Moreover, the process is flexible in terms of the choice of the type of front
      oxide of the transistor, as it is applied in a separate, independent step from
      the application of the surrounding oxide. In case ultimate small dimensions are
      required that go beyond the wafer stepper resolution, the use of e-beam
      technology to produce even smaller structures can be easily integrated.
      Furthermore, the use of a passivation layer opens possibilities for adding
      selectivity via surface modification on silicon dioxide and silicon. After a
      detailed description of the process, the electrical characteristics of the
      devices are shown together with data on the device reliability, indicating that
      the process is easy to manufacture, has a large yield and results in sensor
      devices with electrical characteristics in the desired regime.

PMID- 23882812
TI  - Gas sensors based on alpha-Fe2O3 nanorods, nanotubes and nanocubes.
AB  - Nanorods, nanotubes, and nanocubes of alpha-Fe2O3 were synthesized via a
      hydrothermal process and subsequent calcination treatment. The typical nanorod
      has about 71 nm in width, 7 nm in thickness, and 314 nm in length. The nanotube
      has outer diameter of 90-110 nm, inner diameter of 40-80 nm, and lengths of 250
      400 nm. The nanocubes are rhombus cubes with an edge length of about 680 nm. The
      nanorods, nanotubes and nanocubes were fabricated into chemiresistive sensors.
      The responses (R(a)/R(g)) of the nanotube sensor to ethanol, acetone,
      formaldehyde, and ammonia are greatly higher than those of the nanorod/the
      nanocube sensors. The nanotubes showed enhancing gas-sensitive properties. The
      responses of the nanotube sensor reached 75, 26, 6.8, 1.7 to 200 ppm acetone,
      ethanol, formaldehyde, and ammonia at 270 degrees C and a 30-45% relative
      humidity, respectively, which shows high selectivity. So the nanotubes are gas
      sensing materials more excellent than nanorods and nanocubes.

PMID- 23882813
TI  - Long-term dispersion stability and adhesion promotion of aqueous Cu nano-ink for
      flexible printed electronics.
AB  - Aqueous Cu nanoparticles are synthesized using a reducing agent and surface
      capping molecule which prevents the interparticular agglomeration and surface
      oxidation. Aqueous conductive nano ink is prepared using the resulting Cu
      nanoparticles and conductive Cu layers are prepared via a wet coating process.
      The conductive Cu layers, metalized by annealing at 300 degrees C under vacuum
      atmosphere, exhibit excellent electrical resistivity, showing values as low as 12
      microomega cm. The long-term dispersion stability for three months is monitored
      through an investigation on the rheological behavior of the conductive nano ink
      and the resistivity variation of the conductive Cu layer. The adhesion property
      of the conductive Cu layer is dramatically improved when using a primer-treated
      polyimide film, whereas the conductive Cu layer completely peels off on a
      pristine polyimide film. The epoxy-contained primer plays a critical role as an
      intermediary between the aqueous Cu nano ink and the polyimide film.

PMID- 23882814
TI  - Nano-scale surface morphology evolution of Cu/Ti thin films.
AB  - This paper discusses solid-phase reaction, agglomeration and dendritic growth of
      Cu/Ti/Si thin films with different sublayer thickness, 70 nm Cu/20 nm Ti/Si and
      20 nm Cu/70 nm Ti/Si, annealed using rapid thermal annealing (RTA) method at the
      temperature from 500 degrees C to 800 degrees C. The crystal structure is
      examined using XRD, and the surface morphology is measured by SEM and AFM. The
      sheet resistance is measured using four-point probe method. The dendritic
      patterns can be obtained in both thin films at high temperature but the density
      is not similar. For 70 nm Cu/20 nm Ti/Si thin films, Cu agglomerates at the
      annealed temperature upon to 700 degrees C and thin film is still crystalline
      after 800 degrees C. For 20 nm Cu/70 nm Ti/Si thin films, Cu agglomerated
      completely only after 500 degrees C and thin film has amorphous structure
      annealed after 800 degrees C.

PMID- 23882815
TI  - Synthesis and characterization of Cu3(BTC)2 membranes by thermal spray seeding
      and secondary growth.
AB  - Crack-free Cu3(BTC)2 membranes were successfully prepared by thermal spray
      seeding and secondary growth method. Thermal spray seeding method, combining
      thermal seeding and pressurized spraying, uniformly distributed seed solution on
      the support, anchoring seed crystals tightly on the support. After secondary
      growth of the seeded support in the autoclave, continuous crack-free membrane was
      obtained by controlling cooling and drying steps. The gas permeation test was
      conducted at various temperatures using H2, CO2, CH4 and N2 gases.

PMID- 23882816
TI  - Effect of Mn and P on the macroscopic texture of Ti-Nb stabilized interstitial
      free steels.
AB  - The effect of Mn and P on the macroscopic texture of Ti-Nb stabilized IF steels
      was investigated. In order to examine the evolution of microstructure and
      macroscopic texture during the hot-rolling, cold-rolling and annealing processes,
      microstructure characterization was conducted for hot-rolled, cold-rolled and
      annealed specimens. The initial grain size of hot-rolled specimens was a main
      parameter in determining the development of the macroscopic texture of the
      annealed specimens.

PMID- 23882817
TI  - Functionalized spherical carbon nanostructure/poly(vinylphenol) composites for
      application in low power consumption write-once-read-many times memories.
AB  - We apply functionalized carbon nanoshell and carbon sphere based composites in
      poly(vinylphenol) matrix in write-once-read-many-times memory elements. The
      devices based on carbon nanoshells show an ON/OFF current ratio of 10(5) and long
      term information retention. The functionalized carbon nanoshells and carbon
      spheres show improved dispersion in the poly(vinylphenol) matrix, allowing the
      preparation of homogeneous films even at the submicrometer scale. The low ON
      current allows low power operation, dissipating less than 10(-4) J per square
      meter device active area during the write operation, which is the most energy
      consuming one.

PMID- 23882818
TI  - Theoretical study of new heteroleptic ruthenium complex with conjugated
      phenoxazines.
AB  - In this study, novel ruthenium complexes substituted with donor antenna group
      were designed and studied theoretically to enhance the photovoltaic. We have
      compared the well known N3 dye and Ru(II) complexes substituted with antenna
      groups, such as a conjugated phenoxazine (POZ) of one site, two conjugated POZs
      of both site to bipyridine. Molecular orbital analysis confirmed that the HOMOs
      of N3 are localized over the NCS ligand orbitals of N3, however, the HOMO, HOMO-1
      and HOMO-2 of Ru(dcbpy)(pbpy)(NCS)2 and Ru(dcbpy)(dpbpy)(NCS)2 are localized over
      the NCS or POZ antenna ligand. The TDDFT calculations showed that the complexes
      with POZ donor antenna had panchromatic absorption spectra in the region above
      400 nm compared to N3 dye. Absorption bands between 400 and 500 nm were ascribed
      to transitions of antenna unit. From these results, it is shown that substituted
      antenna moiety enhanced their electronic and optical properties as dye
      sensitizer, and it is expected that these ruthenium complexes with POZ antenna
      would show better performance than N3 dye in conversion efficiency for DSSCs.

PMID- 23882820
TI  - Preparation and characterization of carbon-titania nanocomposite-supported Pd3Co
      alloy nanoparticles for oxygen reduction.
AB  - A TiO2-modified carbon (C-TiO2) has been employed as a catalyst support of Pd3Co
      alloy for electroduction of oxygen. Due to the strong interaction between highly
      dispersed TiO2 and Pd3Co alloy, the C-TiO2 support was shown to be effective for
      a fine dispersion of Pd3Co alloys. The degree of sintering of Pd3Co on C-TiO2
      could largely decrease during heat-treatment for reduction compared to that on
      unmodified carbon support (C). In oxygen reduction reaction (ORR), the reduced
      catalysts (Pd3Co/C-X and Pd3Co/C-TiO2-X; X represents reduction temperature)
      showed higher catalytic performance than their as-prepared catalysts. The
      catalytic activities of Pd3Co/C-TiO2-X were largely enhanced compared to those of
      Pd3Co/C-X. The ORR activity was measured to be the highest on Pd3Co/C-TiO2-300,
      which was 9 times enhanced activity (at 0.85 V) relative to the best-performed
      catalyst supported on carbon (Pd3Co/C-400). A positive role of TiO2 for the metal
      dispersion, the retardation of metal growth during heat-treatment, and the
      modification of electronic structure of Pd3Co was responsible for the enhanced
      ORR performance on Pd3Co/C-TiO2-X.

PMID- 23882819
TI  - Poly(ester amine) synthesized from trimethylolpropane triacrylate and spermine as
      an efficient siRNA carrier.
AB  - Small interfering RNA (siRNA) is a promising candidate for gene therapy due to
      the strong and specific gene silencing effects. However, to effectively silence
      any protein, lack of an efficient delivery system is major obstacle for siRNA
      therapeutics. In the present study, we report on the development of a novel
      poly(ester amine) (PEA) as an efficient siRNA carrier. The PEA was prepared by a
      Michael addition reaction between trimethylolpropane triacrylate (TT) and
      spermine (SPE). The composition of the PEA was characterized by 1H nuclear
      magnetic resonance (1H NMR) and the molecular weight was measured using gel
      permeability chromatography (GPC). This TT-SPE effectively condensed siRNA into a
      compact nanoscale structure (size: 76 nm) with homogenous size distribution and
      provided superior protection of siRNA from RNase A enzyme. Furthermore, TT-SPE/
      siRNA complexes showed good intracellular uptake and had efficacious gene
      silencing effect with low toxicity compared to PEI 25K. These findings
      demonstrated that TT-SPE has potential as an alternative to PEI 25K for siRNA
      based gene therapy.

PMID- 23882821
TI  - Graphene-supported platinum nanoparticles prepared by a self-regulated reduction
      method.
AB  - Graphene-supported Pt nanoparticles were prepared by a self-regulated reduction
      method without using any extra reductive agent. Unassisted reduction of Pt ions
      by the oxygen-containing functional groups on graphene was demonstrated. X-ray
      diffraction (XRD) showed a (200) peak of face-centered cubic Pt crystals and
      energy dispersive X-ray spectroscopy (EDS) further confirmed the presence of Pt.
      Transmission electron microscopy (TEM) depicted good dispersion of the Pt
      nanoparticles on graphene. The particle sizes estimated by TEM and XRD ranged
      from 2 to 6 nm. In comparison, the Pt nanoparticles reduced using ethylene glycol
      as an extra reducing agent exhibited larger sizes, a wider spread of size
      distribution, and less uniform dispersion on graphene. The electrocatalytic
      activity of Pt on graphene was verified by cyclic voltammetry. In addition, Raman
      scattering spectroscopy showed an increase in D- to G-peak ratio and an effect of
      surface-enhanced Raman scattering for the graphene decorated with Pt
      nanoparticles.

PMID- 23882822
TI  - Controlled fabrication of silicon nanowires via nanosphere lithograph and metal
      assisted chemical etching.
AB  - We investigated the controlled fabrication of uniform vertical aligned silicon
      nanowires with desired length, diameter and location by combining nanosphere
      lithograph and metal assisted chemical etching techniques. The close-packed
      polystyrene nanospheres array was obtained by self-assemble technique, followed
      by reactive ion etching to acquire a non-close-packed monolayer template.
      Subsequently, the template was used to create a metal film with nanoholes array,
      which enable the controlled fabrication of ordered silicon nanowires via metal
      assisted chemical etching technique. By adjusting the monolayer of polystyrene
      nanospheres and the conditions for the metal assisted chemical etching, we
      obtained uniform distributed silicon nanowires with desired morphology. The
      aspect ratio of the silicon nanowires can reach to about 86:1. Furthermore, we
      have obtained the double-layer silicon nanowires by slight modifying the process.
      The influences of various conditions during etching were also discussed for
      improving the controlled fabrication.

PMID- 23882823
TI  - Ohmic contacts to N-face p-GaN using Ni/Au for the fabrication of polarization
      inverted light-emitting diodes.
AB  - The electrical properties of Ni-based ohmic contacts to N-face p-type GaN were
      investigated. The specific contact resistance of N-face p-GaN exhibits a linear
      decrease from 1.01 omega cm2 to 9.05 x 10(-3) omega cm2 for the as-deposited and
      the annealed Ni/Au contacts, respectively, with increasing annealing temperature.
      However, the specific contact resistance could be decreased down to 1.03 x 10(-4)
      omega cm2 by means of surface treatment using an alcohol-based (NH4)2S solution.
      The depth profile data measured from the intensity of O1s peak in the X-ray
      photoemission spectra showed that the alcohol-based (NH4)2S treatment was
      effective in removing the surface oxide layer of GaN.

PMID- 23882824
TI  - Physical contribution of Neel and Brown relaxation to interpreting intracellular
      hyperthermia characteristics using superparamagnetic nanofluids.
AB  - In this work, the AC magnetically-induced heating characteristics of various
      viscous nanofluids with either soft ferrite (Fe3O4) or hard ferrite (CoFe2O4)
      superparamagnetic nanoparticles (SPNPs) were investigated to empirically and
      physically interpret the contribution of "Neel relaxation loss power, P(Neel
      relaxation loss)," or "Brown relaxation loss power, P(Brown relaxation loss)," to
      the total AC heat generation of intracellular hyperthermia or in-vivo
      hyperthermia. It was found that the contribution of P(Brown relaxation loss) to
      the total AC heating power, P(totaI), and the specific loss power (SLP) was
      severely affected by the surrounding environment (or in-vivo environment) while
      the contribution of P(Neel relaxation loss) to the P(total) was independent of
      the variation of surrounding environment. Furthermore, all the theoretical and
      experimental results strongly suggested that highly efficacious intracellular
      hyperthermia (or in-vivo hyperthermia) modality can be achieved by enhancing the
      P(Neel relaxation loss) rather than the P(Brown relaxation loss) of SPNP agents
      in nanofluids.

PMID- 23882825
TI  - Rapid synthesis and electrochemiluminescence behavior of CdTe nanoribbons.
AB  - A rapid chemical method has been developed for the synthesis of the CdTe
      nanoribbons with cubic crystalline phase. The method is based on the template
      engaged synthesis in which the Te nanowires were used as template reagents. On
      the basis of a series of experiments and characterizations, the electrochemical
      property of CdTe nanoribbons was determined by the voltammetric technique.
      Furthermore, electrochemiluminescence property of CdTe nanoribbons was
      investigated. The results show that CdTe nanoribbons are helpful to obtain stable
      electrochemiluminescence emission for 1200 seconds.

PMID- 23882826
TI  - A chirality indicator for the surfaces of the silica nanotubes.
AB  - The chirality of the silicas attracted much attention, due to their potential
      applications in asymmetric catalysis and enantioseparation. However, their
      chirality has not been well understood. Herein, a chirality indicator for the
      surfaces of the silica nanotubes was developed. The helical silica nanotubes were
      prepared through a sol-gel transcription approach. The handedness was controlled
      by that of the self-assemblies of the low-molecular-weight amphiphiles. 4
      Triethoxysilyl-1,1'-biphenyl (TSB) was modified on the surfaces of silica
      nanotubes through covalent bonds. The circular dichroism (CD) spectra of the TSB
      modified silica nanotubes indicated that the chirality of silica surfaces could
      be transferred to the twist of the biphenyl rings. The origin of these CD signals
      was characterized using time-dependent density functional theory.

PMID- 23882827
TI  - Ultrafast synthesis of LTA nanozeolite using a two-phase segmented fluidic
      microreactor.
AB  - Fast synthesis of nanosized zeolite is desirable for many industrial
      applications. An ultrafast synthesis of LTA nanozeolite by the organic-additive
      free method in a two-phase segmented fluidic microreactor has been realized. The
      results reveal that the obtained LTA nanozeolites through microreactor are much
      smaller and higher crystallinity than those under similar conditions through
      conventional macroscale batch reactor. By investing various test conditions, such
      as the crystallization temperature, the flow rate, the microchannel length, and
      the aging time of gel solution, this two-phase segmented fluidic microreactor
      system enables us to develop an ultrafast method for nanozeolite production.
      Particularly, when using a microreactor with the microchannel length of 20 m, it
      only takes 10 min for the crystallization and no aging process to successfully
      produce the crystalline LTA nanozeolites at 95 degrees C.

PMID- 23882828
TI  - Triangular ZnO nanosheets: synthesis, crystallography and cathodoluminescence.
AB  - ZnO nanosheets with triangular morphology have been synthesized on an Au-coated
      silicon substrate through a facile thermal evaporation process. The morphologies
      and microstructures of the nanosheets were studied by a scanning electron
      microscope (SEM) and a high-resolution transmission electron microscope (HR-TEM).
      These studies show that a nanosheet is commonly composed of two parts: a
      triangular ZnO sheet and an Au nanoparticle attached on its tip-end. Detailed
      crystallography analyses conclude that the formation of the highly crystalline
      nanostructures can be assigned to a combination of a vapor-liquid-solid (VLS)
      process that is believed to be responsible for its initial nucleation and
      subsequent crystallization along the growth direction, and a vapor-solid (VS)
      process that is responsible for its further radial growth. The spatially-resolved
      cathodoluminescence (CL) spectra exhibit a sharp strong near-band-edge (NBE)
      emission in the ultraviolet range and a negligible green emission.

PMID- 23882829
TI  - Synthesis and characterization of magnesium oxide supported catalysts with a meso
      macropore structure.
AB  - Nanostructured magnesium oxide catalyst support materials with controlled
      morphology and size were synthesized from a supercritical carbon dioxide/ethanol
      solution via chemical reaction of soluble precursors and subsequent thermal
      decomposition. Leaf-like magnesium hydroxide precursors with high specific
      surface area were formed by a low-temperature chemical reaction at below 140
      degrees C, while magnesium carbonate cubes with a very low surface area less than
      3.3 m2/g were formed by temperature-induced phase transition from a loose to a
      dense structure during carbonation reaction at above 150 degrees C. The specific
      surface area has significantly increased higher than 90 m2/g due to the creation
      of highly porous MgO cubes with mesopore structure formed after thermal
      decomposition of the magnesium carbonate precursors. Ni-magnesium oxide catalysts
      with bimodal pore structure were finally formed by the consequence of packing
      heterogeneity of the porous magnesium oxides with different morphologies and
      sizes.

PMID- 23882830
TI  - Developing aspect of carbon coils formation during the beginning stage of the
      process.
AB  - Carbon coils could be synthesized using C2H2/H2 as source gases and SF6 as an
      incorporated additive gas under thermal chemical vapor deposition system. The
      surface morphologies of samples were investigated step by step during the
      beginning stage of the process. After finishing the substrate temperature set to
      750 degrees C, the formation of circular-type nickel clusters were observed in
      places. By setting the total pressure to 100 Torr, most of the circular-type
      clusters were disappeared, whereas a few number of big-sized circular-type
      clusters having several micrometer-sized diameters were infrequently observed.
      After 0.5 minutes deposition reaction, carbon nanofilaments could be observed on
      a specific point of the sample. Further deposition reaction gave rise to the
      increase in the density of carbon nanofilaments as a form of two similar shaped
      carbon nanofilaments sticked together. After 10 minutes deposition reaction, the
      nanosized wave-like carbon coils was formed first and then the formation of the
      microsized carbon coils would be initiated from the nanosized wave-like carbon
      coils.

PMID- 23882831
TI  - Synthesis of Cu/Cu2O nanoparticles by laser ablation in deionized water and their
      annealing transformation into CuO nanoparticles.
AB  - Nano-structured Cupric Oxide (CuO) has been synthesized using pulsed laser
      ablation of pure copper in water using Q-switched pulsed laser beam of 532 nm
      wavelength and, 5 nanosecond pulse duration and laser pulse energy of 100
      mJ/pulse. In the initial unannealed colloidal suspension, the nanoparticles of
      Copper (Cu) and Cuprious oxide (Cu2O) were identified. Further the suspension was
      dried and annealed at different temperatures and we noticed the product (Cu/Cu2O)
      was converted predominantly into CuO at annealing temperature of 300 degrees C
      for 3 hours. As the annealing temperature was raised from 300 to 900 degrees C,
      the grain sizes of CuO reduced to the range of 9 to 26 nm. The structure and the
      morphology of the prepared samples were investigated using X-ray diffraction and
      Transmission Electron Microscope. Photoluminescence and UV absorption
      spectrometry studies revealed that the band gap and other optical properties of
      nano-structured CuO were changed due to post annealing. Fourier transform
      spectrometry also confirmed the transformation of Cu/Cu2O into CuO.

PMID- 23882832
TI  - Morphology-tuned fabrication of highly transparent and flexible nanostructures at
      room temperature.
AB  - Shape controlled fabrication of highly transparent and flexible nanostructures
      (nanocone, nanoneedle, nanowalls) onto nafion substrate were performed at room
      temperature by simple ion irradiation method. By varying the ion incidence angle
      and irradiated ion, the surface morphology and alignment were gradually changed
      from nanocone to nanowall pattern. Interestingly, ion irradiation onto the nafion
      surface led to the systematic pattern without surface modification by external
      addition of any material onto the substrate prior to ion irradiation. The
      antireflective performance of the nanostructures made the surface more
      transparent compared to the bare substrate. The growth mechanism of the
      nanostructures arrays with different shapes is also discussed briefly. This
      straightforward and fast method is thought to be very enticing for surface
      engineering and fabrication of antireflective nanostructures of controlled
      dimension onto different kinds of plastic substrates. These kinds of transparent
      nanostructures might have a remarkable role for promising commercial impact in
      wide variety of areas such as dust-free devices, see-through devices,
      nanofluidics, and drug delivery.

PMID- 23882833
TI  - Template-free synthesis and characterization of monodisperse magnetite hollow
      nanoparticles through solvothermal process.
AB  - Monodispersed Fe3O4 nanospheres with hollow interior structures were synthesized
      without any template. Those nanoparticles exhibited a ferromagnetic behavior with
      a high saturation magnetization of 81.0 emu g(-1). The hollow structure was
      formed based on the aggregation of many primary particles, followed by Oswald
      ripening process. Due to the energy difference between the outer and interior
      particles in the aggregates, the inner particles migrated to the outer shell.
      This resulted in the formation of the empty space inside nanostructures.

PMID- 23882834
TI  - Laser-induced silver nanojoining of gold nanoparticles.
AB  - Gold nanoparticles have been silver-joined to fabricate nanowires by irradiating
      gold nanospheres of 25 nm in diameter and silver nanospheres of 8 nm in diameter
      held together on a carbon-coated copper grid with a 30 ps laser pulse of 532 nm
      for 20 min at a fluence of 3.0 mJ/cm2. Laser-induced nanojoining of silver
      nanoparticles as well as that of gold nanoparticles has also been carried out by
      varying the wavelength and fluence of irradiation laser pulses. Irradiation at an
      optimum condition of laser fluence is essential for the proper silver nanojoining
      of gold nanospheres to produce gold@silver core-shell composite nanowires. The
      excitation of the surface plasmon resonances of the base-metallic gold
      nanospheres rather than the filler-metallic silver nanospheres paves the way for
      the silver nanojoining of gold nanoparticles.

PMID- 23882835
TI  - Direct oxidation growth of P-type semiconducting CuO nanowires.
AB  - P-type copper oxide nanowires (NWs) were grown on metallic copper plates and
      sapphire substrates. Significant variations in the morphology and distribution of
      the NWs, due to underlying differences in the growth mechanism and the NW
      densities, were observed based on the nature of the substrate utilized. The use
      of copper plates induced an extremely high density of copper oxide nanowires on
      temperature-dependent copper oxide layers. However, the sapphire substrates gave
      rise to highly superior CuO NWs without any involvement of an oxide layer,
      leading to a low density of copper oxide NWs. Systematic characterization of the
      as-grown copper oxide NWs using X-ray photoelectron microscopy and Raman
      spectroscopy indicated that the NWs were comprised of CuO with Cu2+ metallic
      ions.

PMID- 23882836
TI  - Biogenic silver nanoparticles with chlorogenic acid as a bioreducing agent.
AB  - We report the synthesis of biogenic silver nanoparticles using chlorogenic acid
      as a bioreducing agent. Chlorogenic acid is a polyphenol compound abundant in
      coffee. UV-Vis spectra showed the characteristic surface plasmon resonance band
      at 415 nm, indicating the successful synthesis of biogenic silver nanoparticles.
      Spherical and irregular shaped nanoparticles were observed with an average
      diameter of 19.29 +/- 8.23 nm. The reaction yield from silver ion to silver
      nanoparticles was observed as 95.43% by using inductively coupled plasma-mass
      spectrometry. Fourier transform infrared spectra revealed that the -C = O groups
      of chlorogenic acid may coordinate or complex into silver nanoparticles. Biogenic
      silver nanoparticles exerted higher antibacterial activity against Gram-negative
      bacteria than against Gram-positive bacteria. Interestingly, a comparable
      antibacterial activity to a standard antibiotic was observed against two strains
      of Pseudomonas aeruginosa (minimum inhibitory concentration of 0.66 microg/mL).
      The synergistic effect of a combination of silver nanoparticles and chlorogenic
      acid on antibacterial activity is obvious, leading to approximately 8-fold
      enhancement in the case of Pseudomonas aeruginosa when compared with chlorogenic
      acid alone. The present report suggests that a pure compound with a plant origin
      is capable of being a bioreducing agent for the synthesis of biogenic silver
      nanoparticles with superior antibacterial activity, opening up many applications
      in nanomedicine and nanobiotechnology.

PMID- 23882837
TI  - The properties of Co- and Fe-doped GDC for low-temperature processing of solid
      oxide fuel cell by electron-beam evaporation.
AB  - This study is transition metal oxides (FeO and CoO) were added to Gd-doped ceria
      (Gd0.1Ce0.9O1.95, GDC) powder for preparing the thin-film electrolyte used in the
      Ni-GDC anode-supported intermediate temperature solid oxide fuel cell (SOFC).
      Recently much attention was aimed at successful powder preparation with high
      sinter activity and conductivity. However, one of the challenges in preparing the
      GDC electrolytes is the densification issue. It is difficult to achieve the
      densification of GDC below 1600 degrees C. To overcome this drawback, attentions
      of the research on the densification of the GDC electrolyte is paid more on
      changing of the fabrication technology, the powder properties, and the sintering
      mechanism. Among them, Fe3+ and Co2+ showed the significant beneficial effect on
      the grain boundary conductivity. So, electrolyte powder made of Co- and Fe-doped
      GDC by solid-state reaction method. And thin-film electrolyte was fabricated on
      the presintered Ni-GDC cermet anode substrate by E-beam evaporating method and
      then co-sintered to form the electrolyte/anode bilayer. We realized crystal
      structure of Co and Fe doped Gd0.1Ce0.9O1.95 (GDC) electrolyte by X-ray
      diffraction (XRD). The morphology was measured by scanning electron microscopy
      (SEM) for the sintered samples were performed. The performance of the cells was
      evaluated over 500-800 degrees C using humidified hydrogen as fuel and air as
      oxidant.

PMID- 23882838
TI  - Investigation the electroplating behavior of self formed CuMn barrier.
AB  - The electrical and material properties of Copper (Cu) mixed with [0-10 atomic%
      manganese (Mn)] and pure Cu films deposited on silicon oxide (SiO2)/silicon (Si)
      are explored. Cu electroplating on self formed CuMn barrier was investigated with
      different Mn content. The electrochemical deposition of the Cu thin film onto the
      electrode using CuMn barrier was investigated. Scanning electron microscopic
      (SEM) micrographs of copper electroplating on CuMn films were examined, and the
      copper nucleation behaviors changed with the Mn content. Since the
      electrochemical impedance spectroscopy (EIS) is widely recognized as a powerful
      tool for the investigation of electrochemical behaviors, the tool was also used
      to verify the phenomena during plating. It was found that the charge-trasfer
      impedance decrease with the rise in the Mn content below 5%, but increase with
      the rise in the Mn content higher than 5%. The result was corresponded to the
      surface energy, the surface morphology, the corrosion and the oxidation of the
      substrate.

PMID- 23882839
TI  - Hydroxyapatite coatings on nanotubular titanium dioxide thin films prepared by
      radio frequency magnetron sputtering.
AB  - In this study, hydroxyapatite (HA) was coated on anodized titanium (Ti) surfaces
      through radio frequency magnetron sputtering in order to improve biological
      response of the titanium surface. All the samples were blasted with resorbable
      blasting media (RBM). RBM-blasted Ti surface, anodized Ti surface, as-sputtered
      HA coating on the anodized Ti surface, and heat-treated HA coating on the
      anodized Ti surface were prepared. The samples were characterized using scanning
      electron microscopy and X-ray photoemission spectroscopy, and biologic responses
      were evaluated. The top of the TiO2 nanotubes was not closed by HA particles when
      the coating time is less than 15 minutes. It was demonstrated that the heat
      treated HA was well-crystallized and this enhanced the cell attachment of the
      anodized Ti surface.

PMID- 23882840
TI  - Few layer graphene matrix for matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry.
AB  - We present the employment of few layer graphene (FLG) as a matrix for the
      analysis of low molecular weight polymeric compounds using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The
      practicality of FLG as a matrix for MALDI experiments is demonstrated by
      analyzing low molecular weight polymers, polar polyethylene glycol (PEG) of 1000
      Da and nonpolar polymethylmethacrylate (PMMA) of 650 Da. The high quality MS
      spectra without low-mass interference signals without any further sampling
      procedure were acquired.

PMID- 23882841
TI  - Synthesis, characterization and biological evaluation of functionalized
      polystyrene particles.
AB  - In this paper we synthesized a series of carboxylate and amino functionalized
      polystyrene nanoparticles with controllable size and surface properties by
      conventional and seed emulsion polymerization methods. They are characterized by
      dynamic light scattering (DLS) and transmission electron microscope (TEM).
      Additionally the content of carboxylate and amino groups on the surface of the
      particles are determined accurately by conductometric titration and fluorescamine
      technique respectively. Afterwards the toxicity of amino modified polystyrene
      particles was tested in 1321N1 astrocytoman cell line and the results showed the
      degree of the toxicity is proportional to the amino content of the particles,
      suggesting the amino group is responsible for the toxicity of the particles.
      Furthermore those particles were labeled by fluorescent dye and confocal
      fluorescent microscopy experiment showed that the particles can be well absorbed
      by cells.

PMID- 23882842
TI  - Nanosized CuO and ZnO catalyst supported on titanium chip for conversion of
      carbon dioxide to methyl alcohol.
AB  - In order to reutilize spent metallic titanium chips (TC) as catalyst support or
      photocatalytic materials, the surface of the TC was modified by thermal treatment
      under air atmosphere. TC-supported nanosized CuO and ZnO catalysts were prepared
      by impregnation (IMP) and co-precipitation (CP) method, respectively. The
      catalytic activity for CO2 hydrogenation to CH3OH was investigated using a flow
      typed reactor under various reaction pressures. The crystals of CuO and ZnO was
      well formed on TC. CO2 conversion, CH3OH selectivity, and CH3OH yield were
      obtained as a function of time on stream over CuO-ZnO/TC catalysts. Conversion of
      CO2 to CH3OH over CuO-ZnO/TC catalyst by CP method and CuO/ZnO/TC catalyst by IMP
      method were ca. 16% and ca. 12%, respectively. Conversion of CO2 over CuO-ZnO/TC
      catalyst by CP method was increased with increasing reaction temperature in the
      range of 15-30 atm. Maximum selectivity and yield to CH3OH over CuO-ZnO/TC at 250
      degrees C were ca. 90% at 20 atm and ca. 18.2% at 30 atm, respectively.

PMID- 23882843
TI  - Synthesis and optical properties of organic fluorescent nanowires and nanotubes.
AB  - The well controlled alpha,alpha'-bis(4-phenyl-1,3-butadienylidene)-acetone (BPBA)
      nanowires and nanotubes were prepared by a template wetting method. The diameter
      and length of BPBA nanowires and nanotubes were identical to template pores,
      diameter -80 nm and length -60 microm. This facile general approach can be used
      for the preparation of nanowires and nanotubes from common small organic
      molecules. The forming of J-aggregates and the geometry of face to face overlap
      of the aromatic rings in BPBA nanowires and nanotubes resulted in clear
      bathochromic shifts of absorption peaks and fluorescence emission peaks compared
      with that of the monomer.

PMID- 23882844
TI  - Mechanical characterization of a single gold nanowire.
AB  - Mechanical properties of gold nanowires were individually determined in this
      investigation using a multifunctional nanomanipulator inside a scanning electron
      microscope (SEM). Gold nanowires were synthesized by an electrochemical
      deposition technique. Three different characterization techniques including
      tensile, buckling and bending tests were adapted to quantitatively determine
      Young's modulus, yield stress and failure stress of the gold nanowires. The
      mechanical characterizations show that the nanowires were highly flexible in
      nature. The excellent resilience and the ability to store elastic energy in these
      nanowires confirm their potential applications in nano electromechanical devices.

PMID- 23882845
TI  - Surfactant size effect on surface-enhanced Raman scattering intensity from silver
      nanoparticles.
AB  - We report on the synthesis of two types of Ag nanoparticles (NPs) and the
      influence of adsorbed surfactant size on the NP surface for surface-enhanced
      Raman scattering (SERS) signals. Both particles were of similar size and
      morphology but were covered by surfactants of different sizes; one surfactant was
      sodium citrate (molecular weight: 258) and the other was sodium polyacrylate
      (molecular weight: 2100). For SERS measurement, 4-mecapobenzoic acid and 4
      naphthalene thiol as Raman-active dyes were immobilized on the surface of each
      AgNP. The signals from Raman-active dyes on AgNPs covered with citrate displayed
      10 times higher intensity than those from polyacrylate-stabilized AgNPs.
      Elemental analysis (EA) revealed that the average weight percentage of sulfur is
      0.94 wt% and 0.12 wt% for citrate-stabilized and polyacrylate-stabilized AgNPs,
      respectively. The sulfur content difference was attributed to the size of the
      existing surfactant influencing the ligand exchange by steric hindrance and
      subsequently the amount of sulfur content of the particles. These experimental
      results suggest that the size of initial surfactant should be taken into account
      when synthesizing a metal particle for enhancing SERS signal.

PMID- 23882846
TI  - Preparation and microstructure of nanocrystalline Ni-Mo films.
AB  - Ni-Mo films were prepared by electrodeposition technique with citric acid as a
      complexing agent. The influence of the main technical parameters such as the
      concentration of Na2MoO4 x 2H2O, the current density, the bath temperature and pH
      on the component content in the Ni-Mo films were investigated by energy
      dispersive spectrometer (EDS), the microstructure and surface morphology of Ni-Mo
      films were characterized by employing X-ray diffractometer (XRD) and scanning
      electron microscope (SEM). The results showed that the excellent Ni-Mo films with
      35.51 wt% Mo was obtained when the concentration of Na2MoO4 x 2H2O was 15 g/L,
      the current density was 8 A/dm2, the bath temperature was 30 degrees C and the pH
      was 5.0. The mircostructure of the Ni-Mo films were nanocrystalline and the
      average size of grain was about 20.12 nm by calculating using Scherrer Equation.

PMID- 23882847
TI  - Growth of carbon nanotubes on surfaces: the effects of catalyst and substrate.
AB  - We report a study of synthesising air-stable, nearly monodispersed bimetallic
      colloids of Co/Pd and Fe/Mo of varying compositions as active catalysts for the
      growth of carbon nanotubes. Using these catalysts we have investigated the
      effects of catalyst and substrate on the carbon nanostructures formed in a plasma
      enhanced chemical vapour deposition (PECVD) process. We will show how it is
      possible to assess the influence of both the catalyst and the support on the
      controlled growth of carbon nanotube and nanofiber arrays. The importance of the
      composition of the catalytic nuclei will be put into perspective with other
      results from the literature. Furthermore, the influence of other synthetic
      parameters such as the nature of the nanoparticle catalysts will also be analysed
      and discussed in detail.

PMID- 23882848
TI  - Dominant formation of the microsized carbon coils by a short time SF6 flow
      incorporation during the initial deposition stage.
AB  - By SF6 gas incorporation for relatively short time during the initial deposition
      stage, carbon coils could be formed on nickel catalyst layer-deposited silicon
      oxide substrate using C2H2 and H2 as source gases under thermal chemical vapor
      deposition system. The characteristics (formation density and morphology) of as
      grown carbon coils were investigated as a function of SF6 flow injection time. 5
      min SF6 flow injection time is appropriate to produce the dominant microsized
      geometry for carbon coils without the appearance of the nanosized carbon coils.
      The geometry for the microsized carbon coils follows a typical double-helix
      structure and the shape of the rings constituting the coils is a flat-type.
      Fluorine's intrinsic etching characteristics for the nanosized carbon coils
      during the initial deposition stage seems to be the cause for the dominant
      formation of the microsized carbon coils in the case of 5-min SF6 flow injection
      time.

PMID- 23882849
TI  - Preparation of ZnO nanowire using sludge from wastewater treatment.
AB  - In this study, we present the synthesis of ZnO nanowire by hydrothermal process
      through reutilization of sludge from soy sauce wastewater electrochemical
      treatment. The influences of floc content and caramel pigment concentration on
      the morphologies of ZnO were studied. The products were characterized by XRD and
      SEM. The results showed that ZnO powder was of hexagonal wurtzite structure and
      well crystallized with high purity. Floc content and caramel pigment
      concentration played an important role in the final morphologies of ZnO
      nanowires. On the basis of these results, a possible growth mechanism for the
      formation of ZnO nanowires was described. These findings not only may contribute
      to control the synthesis of ZnO, but also present a novel method for the disposal
      of wastewater treatment sludge.

PMID- 23882850
TI  - Multilayered graphene in K(a)-band: nanoscale coating for aerospace applications.
AB  - We report on the experimental study of electromagnetic (EM) properties of
      multilayered graphene in K(a)-band synthesized by catalytic chemical vapor
      deposition (CVD) process in between nanometrically thin Cu catalyst film and
      dielectric (SiO2) substrate. The quality of the produced multilayered graphene
      samples was monitored by Raman spectroscopy. The thickness of graphene films was
      controlled by atomic force microscopy (AFM) and was found to be a few nanometers
      (up to 5 nm). We discovered, that the fabricated graphene, being only some
      thousandth of skin depth, provided remarkably high EM shielding efficiency caused
      by absorption losses at the level of 35-43% of incident power. Being highly
      conductive at room temperature, multilayer graphene emerges as a promising
      material for manufacturing ultrathin microwave coatings to be used in aerospace
      applications.

PMID- 23882851
TI  - Hydrothermal synthesis of Fe-doped NiO nanoplatelets with enhanced sensing
      property.
AB  - Ni(1-x)Fe(x)O (x = 0-0.05) nanoplatelets were synthesized by a facile
      hydrothermal process. The crystal structure and morphology of the samples were
      characterized by X-ray diffraction and field emission scanning electron
      microscopy. The incorporation and the valence state of Fe in NiO nanoplatelets
      were determined by X-ray photoelectron spectroscopy. Doping NiO nanoplatelets by
      Fe greatly improves their sensing performance. The Ni0.97Fe0.03O sensor showed
      the highest response up to 59.5 to 100 ppm ethanol at 280 degrees C, which is a
      28.2-fold increase compared to the pure NiO nanoplatelets. The incorporation of
      Fe3+ into the lattice of NiO results in the decrease of the effective hole
      concentrations, which plays a key role for the enhancement of the sensing
      properties. Fe-dopant can be a promising substitute for the noble metal additives
      to fabricate gas sensors with much lower cost. Finally, the gas sensing mechanism
      was discussed.

PMID- 23882852
TI  - Effect of the preparation method of support on the aqueous phase reforming of
      ethylene glycol over 2 wt% Pt/Ce0.15Zr0.85O2 catalysts.
AB  - The effect of catalyst support on the aqueous phase reforming of ethylene glycol
      over supported 2 wt% Pt/Ce0.15Zr0.85O2 catalysts have been investigated. Various
      types of Ce0.15Zr0.85O2 mixed oxides were prepared by hydrothermal precipitation
      (CZH), modified precipitation (CZM), co-precipitation (CZC), sol-gel (CZS)
      methods, respectively. Catalysts were characterized by XRD, N2 sorption analysis,
      and cyclohexane dehydration for relative metal dispersion. The support effect on
      the activity of 2 wt% Pt/Ce0.15Zr0.85O2 catalysts with different preparation
      method was given as follows: CZH < CZM < CZC < CZS. Pt/Ce0.15Zr0.85O2 (CZS)
      catalyst showed good catalytic activity for APR reaction due to its high metal
      dispersion and reducibility. The effect of reaction conditions such as reaction
      temperature, weight hourly space velocity (WHSV) was also studied. The hydrogen
      production rate and hydrogen yield increased in proportion to the reaction
      temperature and corresponding system pressure, whereas WHSV did not affect.

PMID- 23882853
TI  - Photocatalytic degradation of methylene blue over nanosized TiO2 particles
      prepared using the self-propagating high-temperature synthesis method.
AB  - In order to reutilize the spent metallic titanium chips, TiO2 photocatalysts were
      prepared using the self-propagating high-temperature synthesis (SHS) method, and
      were characterized by N2 gas adsorption, X-ray diffraction, and scanning electron
      microscope, particle size distribution. Also, their photocatalytic activities
      were evaluated using methylene blue as a model organic compound. It was confirmed
      that the crystal structure of TiO2 prepared by SHS method was relatively
      homogeneous powder of rutile type. Optimum conditions for photocatalytic
      degradation of methylene blue under UV-C irradiation were methylene blue 9.5 ppm
      in solution and at amount of TiO2 added of 0.02 g/L. In addition, it was found
      that the photocatalytic activity for methylene blue degradation over the prepared
      TiO2 particles was positively related with BET specific surface area.

PMID- 23882854
TI  - Effect of sintering temperature on the thermal properties of diopside-based glass
      ceramics of varying CaO/MgO ratio.
AB  - The thermal properties of diopside (CaMgSi2O6)-based glass-ceramics of varying
      CaO/MgO ratio were investigated as a function of sintering temperature. The
      crystallization behavior of the glass was studied by a non-isothermal method
      using a differential thermal analysis (DTA) with various heating rates. Diopside,
      as a main crystalline phase, and cordierite, as a minor phase, were formed in the
      glass-ceramics with an - 0.67-2.23 CaO/MgO ratio. The X-ray diffraction peak for
      diopside in the glass-ceramic becomes higher with an increase of the CaO/MgO
      ratio. The crystallization volume fraction with sintering temperature was
      calculated showing that both the initiation temperature for crystallization and a
      temperature range of crystallization increased with an increased heating rate.
      The microstructure of all glass-ceramics had a lump area composed of several tens
      of-nanometer particles and a matrix composed of rows of particles, and the matrix
      area decreased with a decreasing CaO/MgO ratio. The thermal conductivity of glass
      ceramics of CaO/MgO = 2.23 was 44% higher than that of CaO/MgO = 0.67 owing to
      the higher crystallinity and less voids in a microstructure. All glass-ceramics
      fabricated in this study were sintered at below 955 degrees C, which makes them
      applicable to the LTCC process for light-emitting diode packaging.

PMID- 23882855
TI  - Nucleation and growth study of nano-PbO2 on Ti in different additives for
      electrocatalytic oxidation process.
AB  - Electrocrystallization of PbO2 on Ti electrode was studied in different bath
      solutions using cyclic voltammetry (CV), chronoamperometry (CA), and scanning
      electron microscopy. The cyclic voltammetry studies revealed that the addition of
      methanol postponed the oxygen evolution region and made over potential nucleation
      of PbO2 on Ti. Oxidation of PbO2 is preferred in second cycle (a peak) in other
      studied bath solutions, except the Nafion and aniline containing solution. In the
      presence of the pyrrole, the PbO2 formed at under deposition potential with less
      in numbers. Nafion and aniline inclusion turn the process in to progressive
      nucleation and growth without inhibition. On the other hand, other solutions
      studied are revealed the instantaneous nucleation and growth or inhibition at
      high potentials. Surface morphology explained that approximately equal to 300 nm
      sizes PbO2 particles with vertical nucleation and growth phenomena evidenced the
      Nafion and aniline are the important dopants. The results indicated that large
      current density or high potential polarization can be obtained in presence of
      methanol, Nafion, and aniline, which is one of the most important and necessary
      factors for forming high surface area PbO2 with strong adherence towards mediated
      electro-oxidation process.

PMID- 23882856
TI  - A study on the electrical, optical, and physicochemical properties of poly(MMA-co
      MAA)/ poly(3,4-ethylenedioxythiophene) hybrid thin films.
AB  - Poly(3,4-ethylenedioxythiophene) (PEDOT) has good properties as a conductive
      polymer such as high conductivity, optical transmittance, and chemical stability,
      while offering relatively weak physicochemical properties. The main purpose of
      this paper is to improve physicochemical properties such as solvent resistance
      and pencil hardness of PEDOT. Carboxyl groups in the poly(MMA-co-MAA) polymer
      chains can effectively crosslink each other in the presence of aziridine,
      resulting in physicochemically robust PEDOT/poly(MMA-co-MAA) hybrid conductive
      films. The electrical conductivity, optical properties, and physicochemical
      properties of the hybrid conductive film were compared by varying the solid
      content and poly(MMA-co-MAA) portion in the coating precursor solution. From the
      results, the transparency and surface resistance of the hybrid film show a
      tendency to decrease with increasing solid content in the coating precursor.
      Moreover, solvent resistance and hardness were dramatically enhanced by
      hybridization of PEDOT and crosslinked poly(MMA-co-MAA) due to curing reactions
      between carboxyl groups. The chemical composition of 30 wt-% of poly(MMA-co-MAA)
      (MMA:MAA mole ratio 9:1) and 3 wt-% - 5 wt-% of aziridine yields the best
      physicochemical properties of poly(MMA-co-MAA)/PEDOT hybrid thin films.

PMID- 23882857
TI  - Pure and Sr(II)-added copper aluminate nanocomposites: structural, electrical and
      alcohol sensing studies.
AB  - The effect of ethylenediamine addition in the sol-gel method for the preparation
      of pure and Sr(II)-added nano copper aluminate (CuAl2O4) composites for the
      enhancement in their structural, electrical, and alcohol sensing properties were
      investigated. The effect of addition of Sr(II) to pure CuAl2O4 in both the
      methods were also discussed. X-ray diffraction, scanning electron microscopy,
      nitrogen adsorption/desorption isotherms, temperature dependant conductance
      measurements and thermoelectric power measurements were used to characterize the
      composites prepared. Among the composites, 0.8 molar ratio strontium added copper
      aluminate composite prepared by modified sol-gel method showed the highest
      sensitivity towards alcohols. The stability, response and recovery of MS-CuSA5
      were also discussed. The response and recovery characteristics showed that the
      order of sensing alcohols by the composites was butanol > isopropanol > ethanol >
      methanol, which could be explained on the basis of oxidation of alcohols.

PMID- 23882858
TI  - Synthesis and optical property of Sb2Se3 nanowires.
AB  - A simple solvothermal approach has been developed for the fabrication of large
      scale single-crystalline Sb2Se3 nanowires. The average diameter of the nanowires
      is about 100 nm, and the length is range from 1 to 2 microm. X-ray diffraction, X
      ray photoelectron spectroscopy, scanning electron microscopy, transmission
      electron microscopy, and electron diffraction were used to characterize the
      samples. The optical property of Sb2Se3 nanowires was characterized by solid
      state UV-visible absorption spectroscopy, and the band gap (E(g)) derived to be
      1.26 eV.

PMID- 23882859
TI  - Iodine assisted low temperature synthesis of 3C-SiC nanostructures and their
      formation process.
AB  - 3C-SiC nanostructures have been synthesized from Si, maltose or glucose and Mg at
      120 degrees C in the presence of I2. The as-obtained products are the mixtures of
      wire-like and tower-shaped SiC nanostructures. Transmission electron microscopy
      (TEM) and scanning electron microscope (SEM) images show that wire-like
      nanostructures are formed by the leaning-type packing of triangular nanosheets
      with the average diameter of 60 nm and tower-shaped nanostructures are formed by
      the level-type packing of nanosheets with the average diameter of 750 nm and
      thickness of about 40 nm. The effects of iodine, reaction time and temperature on
      the morphologies of the final products were also discussed.

PMID- 23882860
TI  - Simultaneous catalyst-free growth of highly oriented ZnO nanowires and
      microtubes.
AB  - Through a catalyst-free chemical vapor deposition method, highly oriented ZnO
      nanowires and microtubes were simultaneously grown on the side and the top
      surface of Si substrate respectively. The ZnO nanowires and microtubes were
      characterized by scanning electron microscopy, X-ray diffraction, transmission
      electron microscopy and selected area electron diffraction. The growth mechanism
      of the microtubes was discussed and the room temperature photoluminescence
      properties of individual microtubes were investigated.

PMID- 23882861
TI  - Rheological behaviors of polypropylene/calcium carbonate nanocomposites under
      axial vibration force field.
AB  - Structures and data processing method of the self-developed multi-function and
      all-electric rheometer (MAR) for polymer composites were introduced.
      Polypropylene (PP)/Calcium Carbonate (CaCO3) nanocomposites were prepared. And
      the homogeneity of the composite was characterized by its rheological behavior.
      With MAR, the effects of vibration parameters on apparent shear viscosity of
      PP/CaCO3 nanocomposites were investigated. The results show that, the viscosity
      of the nanocomposites is much lower in dynamic test with proper vibration,
      comparing with it in corresponding steady-state test at same shear rate. This may
      be caused by the change of microstructure of the composites under vibration. The
      shear viscosity sharply decreases with the increase of vibration amplitude.
      However, the influence of vibration frequency on the shear viscosity of PP/CaCO3
      nanocomposites is insignificant. Therefore, it is a good way to increase the
      superimposed vibration amplitude rather than the frequency to decrease the flow
      resistance. It is useful for discovering the energy saving mechanic of the
      polymer processing introduced the vibration energy into.

PMID- 23882862
TI  - Preparation, characterization of NiB amorphous alloy nanoparticles and their
      catalytic performance in hydrogenation reactions.
AB  - Nano-sized NiB amorphous alloy catalysts were prepared by chemical reduction
      method through introducing AlCl3 into the preparation system. The formation of
      Al(OH)3 sol plays an important role in inhibiting the agglomeration of NiB
      nanoparticles during the reduction process. The NiB amorphous alloy nanoparticles
      could be obtained after the removal of Al(OH)3 by NaOH solution. The particle
      sizes of these alloy catalysts could be adjusted in a certain range by changing
      the amount of AlCl3. The resultant NiB catalysts exhibited high catalytic
      activity in the hydrogenation of furfural and methyl isobutyl ketone, which is
      much higher than the NiB amorphous alloy catalyst prepared by direct reduction
      method. The excellent catalytic performance of NiB nanoparticles is apparently
      owing to the smaller particle size and higher surface area.

PMID- 23882863
TI  - Self-assembled phytosterol-fructose-chitosan nanoparticles as a carrier of
      anticancer drug.
AB  - Self-assembled nanoparticles were synthesized from water-soluble fructose
      chitosan, substituted by succinyl linkages with phytosterols as hydrophobic
      moieties for self-assembly. The physicochemical properties of the prepared self
      assembled nanoparticles were characterized by Fourier transform infrared
      spectroscopy, fluorescence spectroscopy, and transmission electron microscopy.
      Doxorubicin (DOX), as a model anticancer drug, was physically entrapped inside
      prepared self-assembled nanoparticles by the dialysis method. With increasing
      initial levels of the drug, the drug loading content increased, but the
      encapsulation efficiency decreased. The release profiles in vitro demonstrated
      that the DOX showed slow sustained released over 48 h, and the release rate in
      phosphate buffered saline (PBS) solution (pH 7.4) was much slower than in PBS
      solution (pH 5.5 and pH 6.5), indicating the prepared self-assembled
      nanoparticles had the potential to be used as a carrier for targeted delivery of
      hydrophobic anticancer drugs with declined cytotoxicity to normal tissues.

PMID- 23882864
TI  - Environment-friendly route for stable aqueous dispersion of reduced graphene
      oxide for heat transfer application.
AB  - A simultaneous functionalization and reduction route to prepare stable dispersion
      of reduced graphene oxide from graphene oxide has been described. Diethanol amine
      has been introduced for the first time as an environment friendly reducing agent
      in a simple reflux reaction. Diethanol amine acts as a reducing agent and helps
      to enhance the stability of dispersion, making hydrogen bonding by virtue of two
      functional groups. The prepared dispersion of 0.025 mg/mL concentration is stable
      for months together and has a zeta potential value -45 V at room temperature. UV
      Vis study shows peak at 264 nm that is signatory for reduced graphene oxide. TEM
      images confirm spread thin sheets of graphene of few hundred nanometer lateral
      dimension. Thermal diffusivity studies suggest nearly 60% enhancement for the
      dispersion in comparison to base fluid, water. This suggests graphene dispersion
      is promising for heat transfer applications.

PMID- 23882865
TI  - Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation,
      physicochemical characterization and cytotoxicity studies.
AB  - In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid
      co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium
      lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants
      respectively for stabilization. The NPs were prepared by emulsification/solvent
      evaporation method. The combination of these surfactants at weight ratio of 1:0.5
      was able to produce uniformly distributed small sized NPs and demonstrated the
      better stability of NP dispersion with high encapsulation efficiency (85.9 +/-
      0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively.
      The optimized formulation of DTX-loaded PLGA NPs had a particle size and
      polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which
      was further supported by TEM image. In vitro release study was carried out with
      dialysis membrane and showed 32% drug release in 192 h. When in vitro release
      data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which
      suggested the drug was released by anomalous or non-Fickian diffusion. In
      addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability
      reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating
      sustained release from NPs. Therefore, our results demonstrated that
      incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier
      for the treatment of cancer.

PMID- 23882866
TI  - Structural and electrical properties of Ag grid/poly(3,4-ethylenedioxythiophene):
      poly(styrene sulfonate) coatings for diode application through advanced printing
      technology.
AB  - This paper is focused on printed techniques for the fabrication of hybrid
      structure of silver (Ag) grid/poly(3,4-ethylenedioxythiophene):
      Poly(styrenesulfonate) (PEDOT:PSS) on polyethylene terepthalate (PET) as a
      flexible substrate. Ag grid has been printed on PET substrate by using gravure
      offset printing process, followed by PEDOT:PSS thin film deposition on Ag grid
      through electrohydrodynamic atomization (EHDA) technique. The important
      parameters for achieving uniform hybrid structure of Ag grid/PEDOT:PSS through
      printed techniques have been clearly discussed. Field emission scanning electron
      microscope studies revealed the uniformity of printed Ag grid with homogeneous
      deposition of PEDOT:PSS on Ag grid. The optical properties of Ag grid/PEDOT:PSS
      were measured by UV-visible spectroscopy, which showed nearly 80-82% of
      transparency in the visible region and it was nearly same as PEDOT:PSS thin film
      on PET substrate. Current-voltage (I-V) analysis of fabricated hybrid device by
      using printed Ag grid/PEDOT:PSS as a bottom electrode showed good rectifying
      behavior with possible interfacial mechanisms. Capacitance-voltage (C-V) analysis
      was carried over different frequencies. These results suggest that fabrication of
      hybrid structure through printed techniques will play a significant role in mass
      production of printed electronic devices for commercial application by using
      flexible substrate.

PMID- 23882867
TI  - Inter-hospital variation in length of hospital stay after ST-elevation myocardial
      infarction: results from the Belgian STEMI registry.
AB  - OBJECTIVE: The aim of this paper was to assess the determinants of and variations
      in length of hospital stay (LOS) in Belgium after ST-elevation myocardial
      infarction (STEMI). METHODS AND RESULTS: Data on LOS were collected from 2079
      STEMI patients who were discharged alive from 33 Belgian hospitals (21 with PCI
      facilities) during 2010-201 1. Early discharge was defined as hospital discharge
      within 4 days after admission, and the hospitals were clustered according to
      their LOS for low-risk patients. Determinants of LOS were calculated by means of
      a negative binomial regression model. LOS was, on average, 6.5 days with a median
      of 5 days (IQR 4). Baseline risk profiles and reperfusion treatment explained
      only 13% of the LOS variation. Additional analysis revealed major in-hospital
      variations independent of the case mix of patients. For comparable baseline risk
      profiles, the average LOS in a cluster of 11 hospitals with short discharge
      policies was 5.3 + 5.6 days, with an early discharge rate of 58%, while in the
      cluster of 11 hospitals with long discharge policies, the average LOS was 7.9 +
      8.5 days with an early discharge rate of 22% (P <0.0001). Among the clustered
      hospitals, there were no differences with regard to logistics (PCI facility,
      academic affiliation) or volume of STEMI patients. The 1-month mortality rate was
      less than 0.5% in the different clusters of hospitals (p = NS). CONCLUSIONS:
      Length of hospital stay is not only determined by baseline risk profiles of
      patients but is also highly dependent on hospital discharge policy, which seems
      to be unrelated to medical or logistical factors.

PMID- 23882868
TI  - Myocardial fibrosis in rats exposed to low frequency noise.
AB  - Low frequency noise (LFN) characterized by large pressure amplitude (> or =90 dB
      SPL) and low frequency bands (< or =500 Hz) can lead to structural and
      ultrastructural modifications in the extracellular matrix of several tissues,
      with an abnormal proliferation of collagen and development of fibrosis. It is not
      known whether LFN induces similar structural alterations in the ventricular
      myocardium of rats. OBJECTIVE: The aim of this study was to evaluate and measure
      the myocardial fibrosis induced by LFN. METHODS: Two groups of rats were
      considered: group A with 26 rats continuously exposed to LFN during a period of 3
      months; group B with 20 control rats.The hearts were sectioned from the
      ventricular apex to the atria and the mid-ventricular fragment was selected.
      Chromotrope-aniline blue (CAB) staining was used for histological observation.
      The measurement of fibrosis was performed using the computer image analysis Image
      J software. RESULTS: Histological observation with CAB staining showed the
      presence of collagen deposition between the cardiomyocytes. Fibrosis increased
      97.5%, 81.5% and 83.7%, respectively, in the left ventricle, interventricular
      septum and right ventricle, in exposed rats (P <0.001).The ratio fibrosis/muscle
      in left ventricle, interventricular septum and right ventricle was significantly
      higher in LFN exposed rats (P< 0.001). CONCLUSIONS: Our study demonstrates a
      significant myocardial fibrosis induced by low frequency noise in rats. Our
      results reinforce the need for further experimental and clinical investigations
      concerning the effects of low frequency noise on the heart.

PMID- 23882869
TI  - Time-resolved magnetic resonance imaging of contrast kinetics to identify severe
      tricuspid valve regurgitation.
AB  - INTRODUCTION: The gold standard for identifying and grading tricuspid valve
      regurgitation is transthoracic echocardiography. However, the acoustic window
      using transthoracic echocardiography is not always sufficient to quantify the
      amount of regurgitation. Time-resolved imaging of contrast kinetics (TRICKS) is a
      4-dimensional magnetic resonance angiography option with high spatial and
      temporal resolution. The aim of the present study is to find out whether
      identification of patients with severe tricuspid valve regurgitation by using
      TRICKS angiography is feasible. METHODS: TRICKS angiography was performed in a 3T
      CMR-scanner after antecubital injection of gadolinium dimeglumine during breath
      hold. Retrograde appearance of contrast agent in the hepatic veins was classified
      as severe tricuspid regurgitation (TR). Additional semi quantification of
      retrograde perfusion was performed by temporal signal intensity curve (SIC)
      analysis in the hepatic veins close to their drainage into the inferior vena
      cava. Transthoracic echocardiography (TTE) using the actual European guidelines
      on the management of valvular heart disease served as gold standard forTR
      grading. RESULTS: 185 patients (57 +/- 17 years) with TR ranging from no to
      severe TR were analysed prospectively. 14 (7.6%) patients had severe TR, 27
      (14.6%) showed moderate, 137 (74.1%) mild and 7 (3.8%) no TR. TRICKSangiography
      identified 13 patients with retrograde contrast appearance in the hepatic veins,
      of whom all had severe TR in TTE. No patient with echocardiographic mild or
      moderate TR was graded as severe TR using TRICKSangiography. One patient with
      echocardiographic severe TR showed neither in the visual analysis nor in SIC
      analysis retrograde appearance of contrast agent in the hepatic veins. Overall,
      the sensitivity for detecting severe TR using TRICKSangiography was 93% with a
      specificity of 100%. The positive predictive value was 100%, the negative
      predictive value 99%. For severe TR there was no intra- and interobserver
      variability. CONCLUSION: MRTRICKSangiography is a very reliable tool to identify
      patients with severeTR by the imaging of retrograde appearance of contrast agent
      in the hepatic veins. Sensitivity and specificity of this approach is very high
      with no intra- and interobserver variability.

PMID- 23882870
TI  - Light cigarette smoking and vascular function.
AB  - OBJECTIVE: The present study was undertaken to test the hypothesis that smoking
      induces peripheral endothelial dysfunction and altered function in central
      conduit arteries. METHODS: A total of 22 healthy volunteers (10 women and 12 men;
      mean age 25.3 +/- 5.8 years) were included. At baseline, brachial artery
      flowmediated dilatation (FMD), aortic stiffness index (ASI), aortic
      distensibility (AoD), and aortic elastic modulus (AoEM) of all subjects were
      measured. On the 2nd day, the subjects were assigned to smoke either 1 light (0.6
      mg of nicotine, 8 mg of tar, and 9 mg of carbon monoxide) or 1 regular cigarette
      (0.9 mg of nicotine, 12 mg of tar, and 12 mg of carbon monoxide) and the
      measurements were repeated for all subjects 20 minutes following smoking. After
      15 days, the subjects were assigned to smoke 1 cigarette of the type that was not
      smoked on the 2nd day, and the same measurements were performed 20 minutes after
      smoking. RESULTS: In response to smoking 1 light cigarette, FMD values declined
      from 15.0 +/- 6.8% to 9.1 +/- 2.9% (P = 0.002). After smoking 1 regular
      cigarette, FMD values declined from 15.0 +/- 6.8% to 9.4 +/- 4.8% (P= 0.002).
      Aortic elasticity and left ventricular diastolic functions (LVDF) were
      significantly impaired by both types of cigarettes. CONCLUSION: Smoking light
      cigarettes has similar acute detrimental effects on FMD, LVDF, ASI, AoD, and AoEM
      as regular cigarettes.

PMID- 23882871
TI  - Hospitalization costs ofTAVI in one Belgian university hospital.
AB  - OBJECTIVE: Considering the sizeable cost of transcatheter aortic valve
      implantation (TAVI) and conflicting cost-effectiveness studies, it is useful to
      gain more insight into the cost structure of the TAVI hospitalization. This study
      provides such a cost analysis and starts to evaluate options to soften the
      hospitalization cost burden in order to make TAVI economically more feasible.
      METHODS: Costs forTAVI hospitalization in the University Hospital of Antwerp were
      analysed uni- and bivariately. Graphical and numerical displays of the data are
      supplemented with the non-parametric Wilcoxon rank sum statistic and Spearman
      rank rho correlation. RESULTS: Overall, 47 percent of the cost could be
      attributed to the implanted valve and 21 percent was accounted for by the room
      costs. Further, costs seemed highly insensitive to pre-existing patient
      characteristics. Only patients with pulmonary hypertension were characterized
      with systematically higher costs (Wilcoxon rank sum P-value of 0.049).
      Complications related to TAVI had a significant upward impact on the costs and
      there was also evidence for a learning effect on total costs. CONCLUSIONS: In
      general the analyses showed that only limited options remain for cost reduction
      of the TAVI hospitalization cost. The most promising option is the reduction of
      the valve price. Avoidance of complications is hard to achieve given the current
      state of the art although this would significantly reduce overall costs.

PMID- 23882872
TI  - Efficacy of papillary muscle approximation in preventing functional mitral
      regurgitation recurrence in high-risk patients with ischaemic cardiomyopathy and
      mitral regurgitation.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is often complicated by the appearance
      of functional mitral regurgitation (FMR). Although mitral ring annuloplasty (MAP)
      is the most widely used surgical procedure for the surgical treatment of FMR,
      there are still reports of patients who suffer recurrent FMR at later follow-ups.
      We sought to investigate the efficacy of papillary muscle approximation (PMA)
      combined with MAP in preventing the recurrence of FMR in high-risk patients.
      METHODS: One hundred patients with ischaemic (74%) or non-ischaemic (26%) DCM
      along with severe (4+/4+) or moderately severe (3+/4+) FMR were enrolled in this
      prospective, cross-sectional study. According to the interpapillary muscle
      distance (iPMD) and coaptation depth (CD), the patients were risk stratified as
      low (iPMD + CD 30 mm, n= 69) and high-risk (iPMD + CD > 30 mm, n= 31) groups. The
      low-risk patients underwent only MAP, whereas the high-risk patients underwent
      MAP plus PMA. RESULTS: After a mean +/- SD follow-up of 40.8 +/- 12.5 months,
      recurrence of 3+ to 4+ MR was observed in 8 (8.7%) and 7 (11.1%) patients in the
      annuloplasty group (MAP-only) and one (3.4%) patient in the combination group
      (MAP plus PMA) (P= 0.428). At the final follow-up, the New York Heart Association
      (NYHA) function class was 1.57 +/- 0.62 in the annuloplasty group and 1.45 +/-
      0.57 in the combination group; there was no significant difference in NYHA
      function class between the first and final follow-ups (P> 0.05). CONCLUSION: iPMD
      is a valuable index in the riskstratification of the recurrence of post-MAP MR in
      patients with DCM complicated by FMR.The patients treated with MAP plus PMA had
      more favourable outcomes and lower recurrence rates than those treated via the
      traditional route of MAP only.

PMID- 23882873
TI  - An alternative noninvasive technique for the treatment of iatrogenic femoral
      pseudoaneurysms: stethoscope-guided compression.
AB  - OBJECTIVE: latrogenic femoral pseudoaneurysm is a well-known vascular access site
      complication. Many invasive and noninvasive techniques have been proposed for the
      management of this relatively common complication. In this study, we aimed to
      evaluate efficiency and safety of stethoscope-guided compression as a novel
      noninvasive technique in the femoral pseudoaneurysm treatment. METHODS AND
      RESULTS: We prospectively included 29 consecutive patients with the diagnosis of
      femoral pseudoaneurysm who underwent coronary angiography. Patients with a
      clinical suspicion of femoral pseudoaneurysm were referred to colour Doppler
      ultrasound evaluation. The adult (large) side of the stethoscope was used to
      determine the location where the bruit was best heard. Then compression with the
      paediatric (small) side of the stethoscope was applied until the bruit could no
      longer be heard and compression was maintained for at least two sessions. Once
      the bruit disappeared, a 12-hour bed rest with external elastic compression was
      advised to the patients, in order to prevent disintegration of newly formed
      thrombosis. Mean pseudoaneurysm size was 1.7 +/- 0.4 cmx 3.0 +/- 0.9 cm and the
      mean duration of compression was 36.2 +/- 8.5 minutes.Twenty-six (89.6%) of these
      29 patients were successfully treated with stethoscope-guided compression. In 18
      patients (62%), the pseuodoaneurysms were successfully closed after 2 sessions of
      15-minute compression. No severe complication was observed. CONCLUSION:
      Stethoscope-guided compression of femoral pseudoaneurysms is a safe and effective
      novel technique which requires less equipment and expertise than other
      contemporary methods.

PMID- 23882874
TI  - Histomorphometric evaluation of the coronary artery vessels in rats submitted to
      industrial noise.
AB  - INTRODUCTION: Industrial noise (IN) is characterized by high intensity and a wide
      spectrum of wavelengths that induce physical vibration on the body structures.
      This effect, resulting from the low-frequency sound waves, can lead to
      pathological alterations in the extracellular matrix with an abnormal
      proliferation of collagen and development of tissue fibrosis, in the absence of
      an inflammatory process. OBJECTIVE: The aim of this study was to evaluate the
      modifications of the arterial coronary vessels in Wistar rats submitted to IN.
      METHODS: Two groups of rats were considered: group A with 20 rats exposed to IN
      during a maximum period of 7 months; group B with 20 rats as age-matched
      controls.The hearts were sectioned from the ventricular apex to the atria and the
      mid-ventricular fragment was selected. Haematoxylin-eosin and Masson's trichrome
      staining were used for histological observation. Histomorphometric evaluation of
      the coronary vessels was performed using the computer image analysis
      ImageJsoftware. The mean lumen-to-vessel wall (L/W) and media vessel wall-to
      perivascular tissue (W/P) ratios were calculated in each group. RESULTS:
      Histological evaluation showed a prominent perivascular tissue with fibrotic
      development in the absence of inflammatory cells in group A. Histomorphometric
      analysis showed that the mean L/W was 0.7297 and 0.6940 in group A and B,
      respectively. The mean W/P ratio was 0.4923 and 0.5540 in group A and B,
      respectively, being higher in the control group (P <0.01). CONCLUSIONS: There are
      perivascular structural modifications in arterial coronary vessels. Our results
      show a significant development of periarterial fibrosis induced by industrial
      noise in the rat heart.

PMID- 23882876
TI  - Determination of early cardiac deterioration in beta-thalassaemia major by
      echocardiography.
AB  - OBJECTIVES: Cardiovascular involvement is the leading cause of mortality in
      patients with beta-thalassaemia major (beta-TM). This cross-sectional study was
      performed to evaluate the earlier cardiac damage in beta-TM by echocardiography,
      before left ventricular (LV) systolic dysfunction was observed. METHODS AND
      RESULTS: The study population consisted of 70 patients with beta-TM and was
      compared with age- and sex-matched healthy controls (n= 47). The study population
      was divided into subgroups based on serum ferritin levels and the time interval
      from first diagnosis. All patients and control subjects underwent transthoracic
      echocardiography. Mean LV ejection fractions were similar between groups (60 +/-
      5% vs 62+/- 6%, P= 0.063). beta-TM patients had increased left atrial (LA) volume
      index, LV mass index, and right ventricle (RV) diameter index (30.3 +/- 9.9 vs
      19.9 +/- 4.8, 97.0 +/-17.8 vs 80.2 +/- 13.6, and 1.50 +/- 0.17 vs 1.31 +/- 0.15;
      P= 0.0001, respectively). Patients with beta-TM had significantly shortened
      pulmonary acceleration times (133.7+/- 22.4 vs 154.9 +/- 16.5, P= 0.0001). Mitral
      early inflow (E) velocity and tissue Doppler (TDI) annular velocity (Em) ratios
      (E/Em) were also elevated (7.5 +/- 3.0 vs 6.2 +/- 1.6, respectively, P= 0.009).
      Serum levels of ferritin were correlated with interventricular septum (R= 0.308,
      P= 0.009) and posterior wall (R= 0.312, P= 0.009) thicknesses. CONCLUSIONS: It is
      often unsuccessful to reverse iron-induced cardiac deterioration in late-stage
      disease when cardiac failure is already present. Increased LV mass index, LA
      volume index, RV diameter index, and decreased pulmonary acceleration time could
      be earlier parameters featuring premature cardiac remodelling in beta-TM.
      Increased E/Em ratio may also point out early cardiac deterioration in beta-TM
      patients.

PMID- 23882875
TI  - Comparison of radiation-induced damage between CT angiography and conventional
      coronary angiography.
AB  - OBJECTIVE: Both computed tomography (CTA) and conventional angiography (CCA) can
      provide direct visualization of the coronary arteries. The aim of the present
      study was to compare the radiation exposure between CTA and CCA and to search
      whether this amount of radiation causes significant DNA damage. METHOD: Seventy
      two patients who underwent CTA or CCA were enrolled prospectively. We recorded
      the radiation dosage that was used during the procedures and calculated the
      effective dose (ED). We determined the sister chromatid exchange (SCE) level from
      the blood samples which were drawn from the patients before and after the
      procedures. The change in SCE is used as the measure of DNA damage induced by the
      radiation. RESULTS: The patients in the CTA (n = 36) and CCA groups (n= 36) had
      similar baseline characteristics. The ED was higher in CTA examinations compared
      to CCA examinations (14.2 +/- 2.7 vs 6.4 +/- 3.1, P <0.001). The SCE level
      increased significantly after both angiography methods (P <0.001). When the
      change in SCE after angiography was compared, we did not find a significant
      difference among the groups (2.73 +/- 1.6 vs 2.54 +/- 1.22, P= NS). CONCLUSION:
      Although the patients who underwent CTA were exposed to a greater amount of
      radiation, the radiation-induced genetic damage was similar with both types of
      the procedures.

PMID- 23882877
TI  - Prognostic value of elevated mean platelet volume in patients undergoing primary
      angioplasty for ST-elevation myocardial infarction.
AB  - OBJECTIVE: The aim of this study was to evaluate the prognostic value of mean
      platelet volume (MPV) in patients with STEMI undergoing primary percutaneous
      coronary intervention (PCI). METHODS: We prospectively enrolled 495 consecutive
      STEMI patients.The study population was divided into tertiles based on admission
      MPV values. The high MPV group (n= 148) was defined as a value in the third
      tertile (> 8.9), and the low MPV group (n = 347) included those patients with a
      value in the lower two tertiles (< or = 8.9). Clinical characteristics, in
      hospital and six-month outcomes of primary PCI were analysed. RESULTS: Higher six
      month all-cause mortality rates were observed in the high MPV group In Cox
      multivariate analysis; a high admission MPV value (> 8.9) was found to be a
      powerful independent predictor of six-month all-cause mortality. CONCLUSIONS:
      These results suggest that a high admission MPV level was associated with
      increased six-month all-cause mortality in patients with STEMI undergoing primary
      PCI.

PMID- 23882878
TI  - Sinus tachycardia: don't blame the whistle-blower.
AB  - Sinus tachycardia due to sympathetic activation may be the ultimate response to
      support cardiac output. Abrupt heart rate reduction in this condition may be
      deleterious as is illustrated by two cases. Both patients were referred in
      cardiogenic shock after inappropriate treatment with a beta-blocking agent,
      initiated as a symptomatic treatment of a sinus tachycardia.Thus even if beta
      blocking agents provoked a paradigm shift in the understanding of heart failure
      and became a cornerstone of the treatment, therapy should be initiated with
      knowledge of the underlying condition.

PMID- 23882879
TI  - Non-invasive follow-up of a coronary artery pseudoaneurysm after percutaneous
      transluminal coronary rotational atherectomy (PTCRA).
AB  - Percutaneous transluminal coronary rotational atherectomy (PTCRA) is an
      established treatment forvery calcified and/or undilatable coronary lesions. In
      contrast to data from directional coronary atherectomy (DCA) procedures, coronary
      artery aneurysms (CAA) or pseudoaneurysms have not routinely been described as a
      complication after PTCRA. We present a case of a 74-year-old patient, with a
      major CAA, found on a routine control coronary angiogram 4 months after a PTCRA
      of LAD complicated by a coronary perforation. A conservative management guided by
      coronary CT angiography is proposed.

PMID- 23882880
TI  - Congenital absence of the left atrial appendage: a rare anatomical variation with
      clinical significance.
AB  - Congenital absence of the left atrial appendage (LAA) is extremely rare.We
      describe a case of congenial absence of the LAA in a patient scheduled for atrial
      fibrillation (AF) ablation. Absence of the LAA was found pre-procedurally by
      transoesophageal echocardiography (TEE) and cardiac computer tomography (CT).
      During the ablation procedure, the absence was confirmed by contrast injection at
      the usual location of the LAA.

PMID- 23882881
TI  - An unusual case of aortic valve obstruction.
AB  - During a dissection class for anatomy, a white lipoid mass was found in the
      ascending aorta, which was partly attached to the wall and filled the sinuses
      ofValsalva and almost fitting as a cast. This mass prevented full opening of the
      mobile aortic valve leaflets, thereby causing an obstruction. Microscopic
      analysis revealed fibres and presence of polymorphonuclear white blood cells. It
      seems reasonable to assume that this mass has formed in the last weeks or months
      of the life of this subject, which is much quicker than for calcified aortic
      valve stenosis. Therefore, signs and symptoms of aortic obstruction might have
      been missed or misinterpreted. In case of timely detection during life,
      diagnostic imaging and therapeutic approach can be challenging.

PMID- 23882882
TI  - Foetal presentation of long QT syndrome.
AB  - Long-QT syndrome is a rare, inherited cardiac channelopathy that is characterized
      by arrhythmia, syncope and sudden cardiac death. Foetal symptoms are very rare
      and prenatal diagnosis is difficult. We report on a foetal presentation of long
      QT syndrome with severe hydrops and a chaotic heart rhythm at 32 weeks of
      gestation. Postnatal electrocardiography showed runs of polymorphic ventricular
      tachycardia and an extremely prolonged-QT segment (QTc of 640 ms). The initial
      approach of overdrive pacing, followed by the combined therapy of a beta blocker,
      a sodium channel blocker (mexiletine) and potassium suppletion proved successful
      in maintaining a stable sinus rhythm. The girl was doing well at eight months of
      followup. In this patient a timely diagnosis and effective management after birth
      have been life-saving.The intrauterine manifestation of foetal atrioventricular
      dissociation and ventricular arrhythmia should raise suspicion of congenital long
      QT syndrome.

PMID- 23882883
TI  - Cardiac resynchronization therapy in a patient with amyloid cardiomyopathy.
AB  - Cardiac involvement in systemic light chain amyloidosis carries poor prognosis.
      Amyloid deposition in the myocardium can alter regional left ventricular
      contraction and cause dyssynchrony. Cardiac resynchronization therapy (CRT) is an
      effective treatment strategy for patients with advanced heart failure and
      echocardiographic dyssynchrony. We report a clinical and echocardiographic
      response of a patient with amyloid cardiomyopathy, treated with a combination of
      chemotherapy and CRT.

PMID- 23882884
TI  - Left ventricular apical hypoplasia: a case series and review of the literature.
AB  - Left ventricular apical hypoplasia (LVAH) is a rare and newly characterized
      cardiomyopathy. No systemic and detailed case series were reported earlier. We
      report five patients diagnosed with left ventricular apical hypoplasia at our
      institute from 2004 to 2011. All the cases underwent clinical examination,
      eletrocardiography, chest X-ray, transthoracic echocardiography (TTE), and
      cardiac magnetic resonance imaging (CMRI). We described the clinical
      presentations, summarized the imaging characteristics of LV apical hypoplasia,
      and described the associated cardiac malformations. LVAH is characterized by a
      truncated, spherical left ventricle, without a normal apex; the true apex is
      occupied by the right ventricle. In addition, the atrioventricular valve
      anomalies, LV papillary muscle displacement, interventricular and/or interatrial
      septal bulge aneurysms and patent ductus arteriosus structures coexisted in these
      patients. LV apical hypoplasia has distinct appearances that can be easily
      identified on TTE and CMRI. TTE also could accurately define the associated
      cardiac abnormalities.

PMID- 23882885
TI  - Myocardial delayed enhancement by magnetic resonance imaging in a patient with
      Duchenne muscular dystrophy and ventricular tachycardia.

PMID- 23882886
TI  - What's new for ESC congress 2013? (Amsterdam 30th august - 4th September 2013).
AB  - The innovative Spotlight of the Congress is "The heart interacting with systemic
      organs" For our patients, the interaction of cardiac conditions with other organs
      is fundamentally important to outcome, to safety and to clinical management.
      Related specialty areas have much to learn from each other and the ESC Congress
      2013 will attract specialists from other organ systems to help understand disease
      mechanisms and improve the management of our patients.

PMID- 23882887
TI  - Ethnic differences in glycemic control and diabetic ketoacidosis rate among
      children with diabetes mellitus type 1 in the Negev area.
AB  - BACKGROUND: The existent glycemic control of type 1 diabetes mellitus (T 1DM)
      patients in daily practice might not reach the goals determ ied in guidelines.
      Ethnic diversity was also shown to influence glycemic control. OBJECTIVES: To
      evaluate glycemic control, prevalence of diabetic ketoacidosis (DKA) at
      presentation, diabetic complications rate, and associated autoimmune diseases in
      a pediatric Ti M patient population in the Negev area. METHODS: Clinical and
      demographic details of 168 T1iDM patients were evaluated, including HbA1C levels,
      long-term complications, related autoimmune diseases, and insulin pump usage. The
      data were analyzed and the Jewish and Bedouin patient groups compared. RESULTS:
      Only 13.1% of the patients had reached the HbA1C levels recommended by the
      current guidelines at the first and second year follow-up visits, and 9.5% and
      7.1% at the third and fourth year visits, respectively. A significant difference
      in HbAlc levels between Jewish and Bedouin patients was found (P = 0.045 at the
      first year follow-up, P 0.01 thereafter). Significant difference was found
      between the Jewish and the Bedouin groups regarding presentation with DKA, 33%
      and 56% of the patients respectively (P= 0.01). CONCLUSIONS: Existent glycemic
      control in daily practice is far from the guideline goals. Bedouin ethnicity was
      associated with less favorable diabetes control, emphasizing the need for better
      awareness of T1DM and its treatment options in this population. More resources
      should be directed to address T1DM in the general population, especially among
      the Bedouin.

PMID- 23882888
TI  - Association between histological features in temporal artery biopsies and
      clinical features of patients with giant cell arteritis.
AB  - BACKGROUND: In most cases of giant cell arteritis (GCA) the diagnosis is
      confirmed by temporal artery biopsy. Aside from the diagnostic purpose,
      histological parameters may serve as prognostic markers. OBJECTIVES: To review
      positive temporal artery biopsies ofGCA in an attempt to correlate various
      histological parameters with clinical features, disease complications and
      outcome. METHODS: Positive biopsies from 65 GCA patients were randomly selected
      for review by a single pathologist. In each biopsy the following parameters were
      scored: intensity and location of the inflammatory infiltrate, presence of giant
      cells and other cell types, fragmentation and calcification of the internal
      elastic lamina, intimal thickening, and presence of luminal thrombus. Clinical
      data were obtained from the patients' charts. Intensity of the initial systemic
      inflammatory reaction (ISIR) at the time of diagnosis was scored by the presence
      of five parameters: fever, anemia, thrombocytosis, leukocytosis, and
      sedimentation rate >100 mm/hr. RESULTS: In cases with bilateral positive biopsy
      (n=27), there was good correlation between the two sides regarding intensity of
      inflammation (r= 0.65, P< 0.001), location of the infiltrate (r= 0.7, P< 0.001),
      degree of intimal thickening (r= 0.54, P 0.001), and presence of giant cells (r=
      0.83, P< 0.001). The rate of corticosteroid discontinuation tended to be quicker
      in patients with inflammatory infiltrates confined mainly to the adventitia, but
      other histological parameters did not affect this rate. CONCLUSIONS: Inflammatory
      infiltrates confined to the adventitia were associated with more neuro-ophthalmic
      ischemic manifestations, weak/moderate ISIR at the time of diagnosis, and faster
      rate of corticosteroid discontinuation. No association was found between other
      temporal artery biopsy histological parameters and clinical features of GCA
      patients.

PMID- 23882889
TI  - Use of the vessel sealing system in tracheostomy.
AB  - BACKGROUND: Tracheostomy is a frequent, and at times semiurgent, surgical
      procedure. It is performed in close proximity to the thyroid gland, and in many
      cases requires division of its isthmus, putting a patient in danger of
      significant bleeding. OBJECTIVES: To examine prospectively the feasibility of
      vessel sealing in tracheostomy. METHODS: A vessel-seating device was used in 24
      consecutive patients undergoing tracheostomy. There were no exclusion criteria
      for enrolling the patients. No other hemostatic technique was used for dividing
      the isthmus. RESULTS: There were no bleeding events throughout the postoperative
      period. The operating time saving was 5-10 minutes. CONCLUSIONS: Use of the
      vessel sealer was found to be straightforward, efficacious, rapid and safe.

PMID- 23882890
TI  - Current practice in acute flexor tendon repair in Israel.
AB  - BACKGROUND: Various methods of core suture and suture material are used
      successfully in acute flexor tendon repair. OBJECTIVES: To assess the current
      practice in acute flexor tendon repair among Israeli hand surgeons. METHODS: A
      five-question survey was conducted among certified hand surgeons in Israel
      regarding their preferred materials and method for performing acute flexor tendon
      repair. RESULTS: Forty-eight hand surgeons participated in the survey. The most
      widely used core suture in zone 2 (58.3%), as well as in zones 3 and 4 (62.5%),
      was the modified Kessler type. The most widely used suture material was nylon.
      All surgeons incorporated epitendinous sutures to augment their core sutures.
      CONCLUSIONS: The modified Kessler core suture technique is the most widely used
      technique among Israeli hand surgeons for repairing acute flexor tendon
      lacerations in zones 2, 3 and 4. This finding agrees with worldwide data and with
      emerging data attesting to the lower risk of adhesion formation and postoperative
      tendon ruptures with this method. The core suture technique initially popularized
      by the late Prof. Isidor Kessler, who headed our department during the years 1973
      92, remains the most practiced acute flexor tendon repair technique among hand
      surgeons in Israel.

PMID- 23882891
TI  - Newborn screening for congenital cytomegalovirus using real-time polymerase chain
      reaction in umbilical cord blood.
AB  - BACKGROUND: Congenital cytomegalovirus (C-CMV) infection affects 0.4-2% of
      newborn infants in Israel, most of whom are asymptomatic. Of these, 10-20% will
      subsequently develop hearing impairment and may have benetitted from early
      detection by neonatal screeing. OBJECTIVES: To retrospectively anaIyze the
      results of a screening program for C-CMV performed at the Sheba Medical Center,
      Tel, Hashomer, during a 1 year period, using real-time polymerase chain reaction
      (rt-PCR) from umbilical cord blood. METHODS: CMV DNA was detected by rt-PCR
      performed on infants' cord blood. C-CMV was confirmed by urine culture (Shell
      vial). All confirmed cases were further investigated for C-CMV manifestations by
      head ultrasound, complete blood count, liver enzyme measurement, ophthalmology
      examination and hearing investigation. RESULTS: During the period 1 June 2009 to
      31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105
      (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them
      (96%) were confirmed by urine culture. Two additional infants, who had not been
      screened, were detected after clinical suspicion. All 24 infants were further
      Investigated, and 3 (12.5%) had central nervous system involvement (including
      hearing impairment) and were offered intravenous ganciclovir for 6 weeks.
      Eighteen infants (82%) would not otherwise have been diagnosed. CONCLUSION: The
      relatively low incidence of C-CMV detected in our screening program probably
      reflects the low sensitivity of cord blood screening. Nevertheless, this
      screening program reliably detected a non-negligible number of infants who could
      benefit from early detection. Other screening methods using saliva should be
      investigated further.

PMID- 23882892
TI  - Diagnosis of colon cancer differs in younger versus older patients despite
      similar complaints.
AB  - BACKGROUND: Colon cancer is common, affecting mostly older people. Since age is a
      risk factor, young patients might not be given the same attention as older ones
      regarding symptoms that could imply the presence of colon cancer. OBJECTIVES: To
      investigate whether young patients, i.e., under age 50, complain of symptoms for
      longer than older patients until the diagnosis of colon cancer is established.
      METHODS: In this retrospective cohort study, patients were divided into two
      groups: < 50 years old (group 1) and > or = 50 (group 2). All had undergone
      surgery for left or right-colon cancer during the 10 year period of the study
      from January 2000 through December 2009 at one medical center. Rectal and sigmoid
      cancers were excluded. Data collected included age, geander, quantity and quality
      of complaints, duration of complaints, in-hospital versus community diagnosis,
      pathological staging, the side of colon involved, and overall mortality. The
      primary outcome was the quality and duration of complaints. Secondary outcomes
      were the pathological stage at presentation and the mortality rate. RESULTS: The
      study group comprised 236 patients: 31 (13.1%) were < 50 years old and 205
      (86.9%) were > or = 50. No significant difference was found in the quantity and
      quality of complaints between the two groups. Patients in group 1 (< 50 years)
      complained for a longer period, 5.3 vs.2.4 months (P= 0.002). More younger
      patients were diagnosed with stage IV disease (38.7% vs. 21.5%, P= 0.035) and
      fewer had stage I disease (3.2% vs. 15.6%, P= 0.06); the mortality rates were
      similar (41.9% vs. 39%). Applying a stepwise logistic regression model, the
      duration of complaints was found to be a predictor of mortality (P= 0.03, OR 1.6,
      95% CI 1-3.6), independently of age (P= 0.003) and stage (P< 0.001). CONCLUSIONS:
      Younger patients are more often diagnosed with colon cancer later, at a more
      advanced stage. Alertness to patients' complaints, together with evaluation
      regardless of age but according to symptoms and clinical presentation are
      crucial. Large-scale population-based studies are needed to confirm this trend.

PMID- 23882893
TI  - Occupational exposures and symptoms among firefighters and police during the
      carmel forest fire: the Carmel cohort study.
AB  - BACKGROUND: From 2 to 5 December 2010, Israel experienced the most severe forest
      fire In its history, resulting in the deaths of rescue workers. Little research
      exists on the health risks to emergency responders during forest fires, and there
      is no published research to date on occupational health among firefighters in
      Israel. OBJECTIVES: To describe the exposures experienced by emer gency
      responders to smoke, fire retardants and stress; the utilization of protective
      equipment; and the frequency of corresponding symptoms during and following the
      Carmel Forest fire. METHODS: A cohort of 204 firfighers and 68 police who took
      part in rescue and fire-abating activites during the Carmel Forest fire were
      recruited from a representative sample of participating stations throughout the
      country and interviewed regarding their activities during the fire and their
      coinciding symptoms. Unpaired two-sample t-test compared mean exposures and
      symptom frequency for firefighters and police. Chi-square estimates of OR and
      95%CI are provided for odds of reporting symptoms, incurring injury or being
      hospitalied for various risk factors RESULTS: Of the study participants, 87%
      reported having at least one symptom during rescue work at the Carmel Forest
      fire,with eye irritation (77%) and fatigue (71%) being the most comon.
      Occupational stress was extremely high during the fire; the average length of
      time working without rest was 18.4 hours among firefighters. CONCLUSION:
      Firefighter and police were exposed to smoke and ocupational stress prolonged
      periods during the fire. Further research is needed on the residual health
      effects from exposure to forest fires among emergency responders, and to identify
      areas for improvement in health preparedness.

PMID- 23882894
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy: revisiting the role of
      intravenous immmunoglobulins.

PMID- 23882895
TI  - Achieving the management goals of type 1 diabetes in children and adolescents: is
      it feasible?

PMID- 23882896
TI  - Vital hepatitis reactivation with anti-tumor necrosis factor-alpha: what do we
      know?

PMID- 23882897
TI  - Trans-radial coronary interventions: a "win-win" for both patient and operator.

PMID- 23882898
TI  - Hepatitis B and C reactivation with tumor necrosis factor inhibitors: synopsis
      and interpretation of screening and prophylaxis recommendations.
AB  - Information on reactivation of chronic viral hepatitis infection in patients who
      are candidates for tumor necrosis factor alpha inhibitors (TNFi) is in a constant
      state of flux. We retrieved the most updated guidelines (in English) of prominent
      rheumatological and gastroenterological professional socienties for the mangement
      of chronic hepatitis B (HBV) and hepatitis C virus (HCV) infection in the context
      of treatment with TNFi. Subsequently, the major areas of uncertainty and absence
      of consensus in the guidelines were located and a secondary search for additional
      studies addressing those areas was performed. Based on our search we formulated a
      personal interpretation applicable to health care settings with virological
      laboratories capable of performing viral load measurements, and health systems
      that can support use of potent nucleoside/tide analogues in well-defined patient
      populations.

PMID- 23882899
TI  - Biomedical synthetic biology: an overview for physicians.
AB  - Synthetic bioiogy is a ,relatively new fieild of bologlcal research and
      development that focases on the engineering of genetic molecular machlnes wIth a
      specific predefined function. Plainly put the newly engineered organism functions
      as a machine. It can process information. manufature, heal and even diagnose. We
      just have to engineer It to do so. The famous quote "Biology Is the
      nanotechnology that works" is currently being put to the test on a worldwide
      scale. The application of these machines Is theoretically boundless. In
      laboratories worldwide synthetic biology technologies are being rationally
      designed to assist in diagnosis or disrupt disease mechnisms. In the not too
      distant future they are expected to reach the clinical setting. This new field
      should be distinguished from classic genetic engineering. The latter researches
      naturalfy found DNA segments via cloning. It is weakly associated with
      engineering. Synthetic biology focuses on the engineering of molecular biological
      machines for the benefit of mankind. This is done via synthetic (computer
      printed) DNA sequences, man-designed or altered in silico. In this article I will
      briefly introduce synthetic biology, elaborate on the BiobrickFoundation as an
      independent fast-growing synthetic biology-sharing movement, and report on
      selected developing applications for medicine.

PMID- 23882900
TI  - Arteriovenous fistula after cardiac catheterization from a radial approach.

PMID- 23882901
TI  - Amyloid tumor behaving as localized amyloidosis in a patient with long history of
      asymptomatic light chain myeloma.

PMID- 23882902
TI  - Granulomatous gastritis and Helicobacter pylori infection.

PMID- 23882903
TI  - Enteroviral myocarditis requiring extracorporeal membranous oxygenation in a 2
      week old girl.

PMID- 23882904
TI  - Progressive multifocal leukoencephalopathy in an HIV-negative patient following
      treatment with rituximab.

PMID- 23882905
TI  - Third-degree chemical burns from chlorhexidine local antisepsis.

PMID- 23882906
TI  - Military medicine.

PMID- 23882907
TI  - Questionable eponyms.

PMID- 23882908
TI  - Paraparesis and rhabdomyolysis.

PMID- 23882909
TI  - [Pain assessment: the end of subjectivity?].

PMID- 23882910
TI  - [Glial cells and chronic pain: from the laboratory to clinical hope].
AB  - Despite their high prevalence, associated disability and seemingly rich
      pharmacopeia, the various forms of chronic pain remain frequently intractable.
      The past decade witnessed the rise of a concept stating that non-neuronal cells
      of the central nervous system, astrocytes and microglia, are crucial elements in
      pathological pain. This review gathers and summarizes the experimental data
      underpinning this theory in animal models and addresses their pertinence in
      humans. The potential opportunities and constraints of glial inhibition are
      exposed and compared to more moderate strategies of selective modulation. This
      therapeutic hope is particularly highlighted in our discussion of the first
      completed clinical trials employing glial inhibitors in the treatment of chronic
      pain.

PMID- 23882911
TI  - [New concepts in the pathophysiology, diagnosis and treatment of neuropathic
      pain].
AB  - We here summarize five articles bringing new advances in our knowledge on
      neuropathic pain and put them into perspective with our current understanding.
      The first uses a mechanism-based approach with a capsaicin test to stratify
      patients suffering from painful diabetic neuropathy before starting a topical
      clonidine treatment. The second reviews disinhibition as a critical mechanism and
      a promising target for chronic pain. The third evokes neuroglial interactions and
      its implication regarding the interplay between injuries in childhood and
      hypersensitivity in adulthood. The last articles remind us that interventional
      therapies, not always very invasive, have a future potential in the therapy of
      frequent conditions such as head pain disorders.

PMID- 23882912
TI  - [Imaging in low back pain: limits and reflexions].
AB  - Lumbar imaging is frequently requested in patients with low back pain for various
      reasons. However, the prevalence of severe lesions, including neoplastic, is only
      about 1%. Imaging in the absence of clinical suspicion performs poorly.
      Similarly, the imagery is no more likely to identify the anatomical structures
      that are the source of pain for patients with low back pain. Finally, the
      literature shows that the impact on treatment decisions and the effect on quality
      of life of patients cannot justify an indiscriminate use of these investigative
      techniques. Without questioning the value of imaging, the practitioner must keep
      in mind these limitations in order to optimize the use of this resource.

PMID- 23882913
TI  - [Efficient treatment of breakthrough pain in adults: the importance of timing and
      medication choice].
AB  - Diagnostic or therapeutic procedures can lead to breakthrough pain. Thanks to a
      wise choice of analgesic medication started in due time, this type of pain can be
      avoided or decreased. The therapeutic options of this preventive approach are
      presented according to the expected breakthrough pain type and intensity.
      Specific situations are presented through case discussions. The main
      pharmacokinetic information needed to prescribe the right analgesic at the right
      time is summarized in a convenient table. When associated to non-pharmacological
      measures such as empathy, patient positioning and high quality procedures,
      preventive analgesia provides patients the best possible relief from breakthrough
      pain.

PMID- 23882914
TI  - [Learning self-management for pain. Potentials and limits of an Internet website
      for low back pain].
AB  - This paper examines the role of an interactive website--named Oneself--on
      patients' chronic low back pain self-management in the Italian part of
      Switzerland. As part of a qualitative evaluation, we conducted semi-structured
      interviews with a purposive sample of 18 Oneself users. Results confirm that the
      Internet may promote attitudes and behaviors of self-management of chronic low
      back pain. However, it seems that individuals take advantage of this means
      differently, based on their profile (age, familiarization with the web) and stage
      of advancement in the self-management process. We conclude that information and
      support provided online should be tailored according to these different criteria.

PMID- 23882915
TI  - [Medically unexplained persistent pain syndrome: psychoanalytic approach].
AB  - Chronic persistant pain is very challenging as the patient and his/her therapist
      are confronted with a lack of explanation about the origin of pain. The
      relationship has also to face many obstacles such as psychological strain or
      psychosocial tensions such as disagreements about the patients working capacity.
      Nevertheless continuing attention from a solid and secure therapist may
      progressively lead to changes in pain experience, the emergence of emotions and
      improved therapist patient interactions.

PMID- 23882916
TI  - [Questions and answers regarding the use of rivaroxaban in daily practice].
AB  - Several new oral anticoagulants are now on the Swiss market and the general
      practitioner faces new challenges regarding the management of these new drugs.
      This consensus document aims to answer to the most frequently asked questions
      regarding rivaroxaban and covers different topics such as indications, initiation
      of treatment, drug-drug interactions and perioperative management.

PMID- 23882917
TI  - [Anaphylaxis].

PMID- 23882918
TI  - [Endometriosis, an underestimated disease: reducing pelvic pain effectively and
      lastingly].

PMID- 23882919
TI  - [Emergency treatment for Middle Eastern coronaviruses (MERS-CoV].

PMID- 23882920
TI  - [Simulate suffering?].

PMID- 23882921
TI  - [Yesterday, Viagra was a medication].

PMID- 23882922
TI  - [Traveler's syndromes and medical repatriation].

PMID- 23882923
TI  - [Free contraceptive for teenagers?].

PMID- 23882924
TI  - [Practices and structures to reverse].

PMID- 23882925
TI  - [Neutrophils and hyaluronians in carcinogenesis].
AB  - Inflammatory processes involving polymorphonuclear leukocytes (PMNL) play an
      important role in cancer. PMNL can affect the formation and growth of the tumor.
      Cancer cells produce significant amounts of hyaluronans (HA), which pass into the
      extracellular space and are responsible for the inhibition of PMNL function
      through TLR4 receptor, and increase in the production of IL 10 the
      immunosuppressive cytokine as well as the other proinflammatory cytokines. HA
      supported the metastasis of cancer cells by binding to the CD44 receptor on
      endothelial cells. Increased PMNL--Lymphocyte ratio as a negative prognostic
      factor indicates also the important not defined role of PMNL in carcinogenesis.

PMID- 23882926
TI  - [Transmission of Mycobacterium tuberculosis pre-XDR strains belonging to the
      Beijing family].
AB  - Tracking transmission of Mycobacterium tuberculosis strains in a population of
      humans and animals is the basis of modern epidemiology of tuberculosis. Molecular
      methods are used for the analysis of small patient population, as well as a
      global studies, which monitor the variation and geographic distribution of
      mycobacteria. A special role is played by genotyping methods that allow to
      control the spread of drug-resistant-TB and Beijing-TB. Beijing strains,
      especially drug-resistant clones, are regarded as one of the most dangerous
      mycobacteria. They have a high pathogenicity, the ability to rapidly acquire drug
      resistance and unpredictable response to treatment. The aim of this study was
      molecular and epidemiological analysis of M. tuberculosis Beijing strains
      isolated from patients with pre-XDR-TB, detected in Poland, and investigate the
      probable route of transmission of infection between patients. MATERIAL AND
      METHODS: Material for analysis was a collection of more than 10,000 strains of M.
      tuberculosis collected in the years 2001-2011 in the National TB Reference
      Laboratory at the National Tuberculosis and Lung Diseases Research Institute in
      Warsaw. Analysis of phenotypic resistance to primary and secondary drugs allowed
      the selection of 47 pre-XDR strains, and genotyping--18 pre-XDR-Beijing strains.
      Molecular analysis included 2 genotyping methods--spoligotyping and MIRU-VNTR
      analysis. RESULTS: Genotyping results allowed the identification of 5
      epidemiological groups of 13 patients with pre-XDR-Beijing-TB, between which
      transmission could occur. Based on the available epidemiological and demographic
      data, it was found that in isolated groups, 5 patients could be in close or
      casual contact. CONCLUSIONS: This analysis shows that in Poland, one of the
      causes of drug resistance and the spread of M. tuberculosis Beijing type, is the
      transmission of infection between patients. This observation requires conducting
      active molecular and epidemiological investigations among patients, as well as
      studies of people with their environment.

PMID- 23882927
TI  - [Evaluation of the relationships between plasma homocysteine level and selected
      low-grade inflammation indices according to the prevalence of metabolic syndrome
      in men].
AB  - Metabolic syndrome (MS) is associated with low-grade systemic inflammation.
      Hyperhomocysteinemia is considered recently as a consequence of immune
      activation. Acute phase proteins, proinflammatory cytokines and probably
      homocysteine (hHcy) are involved in the pathogenesis of MS, atherosclerosis and
      ageing. The aim of our study was to investigate the reciprocal links between hHcy
      and selected negative and positive acute phase reactants as well as interleukin
      18 in men over 40 years of age suffering from MS compared to healthy subjects.
      MATERIAL AND METHODS: In 160 randomly selected men aged 40 to 70 years hHcy, C
      reactive protein, transferrin, alpha1-antichymotrypsin and IL-18 were evaluated
      and features of MS using IDF (International Diabetes Federation-2005) criteria
      were estimated. RESULTS: Hcy plasma levels are not correlated with age. Men
      suffering from MS revealed significantly higher serum hHcy levels than healthy
      subjects (11.52 +/- 6.87 microM/L vs 10.08 +/- 5.44 microM/L, p = 0.0074). A weak
      but positive (r = 0.099; p = 0.014) correlation between hHcy and the numbers of
      MS traits is shown. However, the plasma hHcy level is correlated only with HDL
      cholesterol serum levels (r = -0.132; p = 0.035) and fasting blood glucose (r =
      0.164; p = 0.009). hHcy concentration is strongly positively correlated with IL
      18 (r = 0.276; p = 0.005), although not with CRP, alpha1-ACT and transferrin.
      CONCLUSIONS: In men over 40 years of age suffering from MS significant higher
      serum Hcy levels than healthy subjects are presented, but hHcy (as opposed to
      acute phase reactants) correlates only with IL-18 plasma concentrations.

PMID- 23882928
TI  - [Influence of functional status of ovaries on results of controlled ovarian
      hyperstimulation].
AB  - The controlled ovarian hyperstimulation is an integral part of infertility
      treatment. Its main objective is to obtain oocytes with a highest developmental
      potential. The stimulation protocols involving the gonadotropin-releasing hormone
      analogues and gonadotropins are considered as the most efficient. Despite many
      years of use, some aspects of controlled ovarian stimulation has not yet been
      clarified, especially the role of the functional status of ovaries before
      hormonal stimulation. The aim of study was to assess the influence of the
      functional status of ovaries on the results of the controlled ovarian
      hyperstimulation. MATERIALS AND METHODS: The retrospective study included female
      patients suffering from infertility The patients were divided into two groups
      depending on ultrasonographic appearance of ovaries before controlled ovarian
      hyperstimulation. The patients with small antral follicles < 6 mm in diameter
      were selected into group I. The patients with five or more antral follicles > or
      = 8 mm in diameter in each ovary were included into group II. The patients from
      both groups underwent similar treatment process. The major area of interest was
      the number, type and quality of oocytes obtained from patients from both groups
      after ovarian puncture. RESULTS: A retrospective study was conducted on 635
      infertile patients (group I 382, group II 253). Altogether, 4055 oocytes were
      obtained in the group I and 2555 oocytes in the group II. The mean number of MII
      oocytes in group I was 9,2 and 8,7 in group II; p < 0.05. There were
      significantly more MI oocytes in group I than II. The mean numbers of immature
      oocytes were comparable between groups. The athretic and dysmorphic oocytes were
      more prevalent in group II. CONCLUSIONS: The results of the present study
      indicates that the functional status of ovaries before controlled ovarian
      hyperstimulation plays pivotal role for the treatment outcome.

PMID- 23882929
TI  - [Arylsulfatase activity in the blood of men with malignat melanoma. Preliminary
      reports].
AB  - High arylsulfatase activity occurs in the course of cutaneous melanoma. There is
      a correlation between the activity of the enzyme, and the susceptibility to
      metastatic cancer, including metastatic melanoma. Melanoma of the skin were 1.4%
      of all cancers in men and the number of deaths from this cancer in Poland in 2002
      was the 424th. The aim of the study was decided to determine the usefulness of
      arylsulfatase activity in patients with melanoma of men for diagnostic purposes
      and for monitoring of the disease course. MATERIAL AND METHODS: The study
      included 25 patients diagnosed men with melanoma (mean age 55.5 years). Blood
      samples were collected before excision of melanoma of the skin and in the period
      from 2 to 3 months after surgery. To donate blood after resection of malignant
      melanoma reported only 13 men (mean age 57.4 years). Arylsulfatase activity was
      determined by Roy the modified Bleszczynski method. RESULTS: Arylsulfatase
      activity before surgery to remove the changes was higher in comparison to the
      control group and the patients after surgery. CONCLUSIONS: Of men patients with
      malignat melanoma arylsulfatase activity was high. Arylsulfatase mark may be
      useful in diagnosing and monitoring the course of the disease.

PMID- 23882930
TI  - [The evaluation of cost-effectiveness and cost-utility of valganciclovir for the
      prophylaxis of cytomegalovirus disease to 200 days after kidney transplantation].
AB  - Standard procedure for cytomegalovirus disease (CMV) prophylaxis in kidney
      transplant patients was the administration of valganciclovir for up to 110 days
      after organ transplant. This prophylaxis has been extended up to 200 days in
      Poland since 2011. The decision was based on the results of clinical trials which
      showed significant clinical benefit in case of prolonged administration of the
      drug. The aim of the analysis was to provide the economic evaluation of extending
      the CMV prophylaxis with co-financed from public funds Valcyte (valganciclovirum;
      60 tab. a 450 mg; Roche Polska Sp. z o.o.) from 110 to 200 days, in the high risk
      patients group after kidney transplant (seronegative recipient and infected
      donor, D+/R-). The analysis was performed from the Polish healthcare payer's
      perspective. MATERIAL AND METHODS: All methods used in the following study were
      consistent with the Requirements of the Polish HTA Agency (AHTAPOL). The cost
      effectiveness and the cost-utility analysis were performed on the basis of a
      randomised study which was identified as a result of the systematic search of the
      medical databases, comparing 200 days valgancyclovir administration with 100 days
      drug use as a prophylaxis of CMV disease in the patients group mentioned above.
      The Markov model was developed, simulating the disease evolution over time
      considering a high risk patient after kidney transplant treated with
      valgancicloviras the CMV disease prophylaxis. The disease period was divided into
      health states that are the most probable for this condition and the transitions
      probabilities between them were identified and assigned. Based on the clinical
      trial results, registry database of health conditions usability and experts'
      opinion, all health states (i.e. death, kidney transplant, CMV disease) were
      attributed with utilities and costs. The direct costs, important from the Polish
      healthcare payer's perspective, were included in the analysis. Extension of the
      proposed model in the series of one month time cycles made it possible to assess
      long-term (assumed time horizon was median patient's life expectancy--23,5 years)
      costs and clinical effects of the compared technologies. RESULTS: The Incremental
      Cost-Effectiveness Ratio (ICER) was 39 669 008 PLN and The Incremental Cost
      Utility Ratio (ICUR) was 48 008 PLN in the specified time horizon. The result is
      well below the accepted threshold of profitability in Poland (assuming tripled
      GDP per capita cost-utility threshold, i.e. 99 543 PLN), which means that the
      therapy is cost-effective. CONCLUSIONS: The results of the analysis confirmed
      that the 200 days use of valganciclovirin the prevention of CMV disease compared
      to standard 110 days therapy is economically justified from the Polish healthcare
      payer's perspective.

PMID- 23882931
TI  - [Comparison of the prevalence of cleft lip and/or palate in children in Lodz
      province in the period of 1996-2010 in 5-years intervals].
AB  - Clefts of lip and/or palate are the most common facial malformations. Taking into
      consideration complexity of this defect and necessity of multidisciplinary
      treatment the knowledge of actual scale of this phenomenon seems to be relevant.
      The aim of this paper it to describe and to compare the prevalence of cleft lip
      and/or palate in Lodz province in the period of 1996-2010 in 5 years intervals.
      MATERIAL AND METHODS; From Polish Register of Congenital Malformations we managed
      to obtain the data of the number of live born infants and birth of children with
      clefts in Lodz province in 2001-2010. On the basis of previously performed
      studies Department of Plastic, Reconstructive and Esthetic Surgery has the data
      of clefts' prevalence in Lodz province from year 1996 to 2000. RESULTS: The mean
      frequency of clefts was 1,67/1000 live born infants in 1996-2000, during years
      2001-2005 - 1,47/1000, and 1,13/1000 in 2006-2010. CONCLUSIONS: Significant
      decrease of the prevalence of cleft lip and/or palate is observed in Lodz
      province in the period of 1996-2010. In boys the most frequent defect is cleft
      lip and palate, while in girls--isolated cleft palate.

PMID- 23882932
TI  - [Reversible pulmonary hypertension as a consequence of dasatinib treatment in a
      patient with chronic myeloid leukemia and scleroderma].
AB  - Pulmonary hypertension may be associated with many clinical conditions, including
      connective tissue diseases. We present a case of a patient with sclerodermia and
      chronic myeloid leukemia, who developed severe symptoms of pulmonary
      hypertension. Atypical clinical course of pulmonary hypertension, including
      complete remission of clinical symptoms and hemodynamic improvement provoked
      critical approach to the etiology of pulmonary hypertension. Taking into account
      the temporal coincidence with the use of dasatinib (a tyrosine kinase inhibitor)
      and a few case reports in the literature, it appears that reversible pulmonary
      hypertension in our patient was associated with the use of dasatinib.
      Sclerodermia in a previous medical history, an acknowledged risk factor for
      pulmonary hypertension, initially delayed the correct diagnosis. Reclassification
      changes the clinical prognosis of pulmonary hypertension in this specific case
      and allowed to terminate of specific treatment of pulmonary hypertension with
      good results.

PMID- 23882933
TI  - [The use of hemostatic agent Tachosil in surgical treatment of kidney cancer
      infiltrating liver--case report].
AB  - The right kidney cancer very rarely locally invades the liver as compared with
      blood metastasis which occur more frequent. In these cases, the only extensive
      surgical resection of part of the liver gives the opportunity to improve survival
      dependent on kidney cancer. In the intra-and postoperative bleeding and leakage
      of bile from the liver cut surface is a complication that it depends on the
      success of the treatment. A valuable complement to traditional ways of obtaining
      hemostasis is sealed section of liver collagen patches of horse, which are
      covered with tissue adhesive supplemented human fibrinogen and thrombin
      (Tachosil). The aim of this study is to present the case of 38-year-old woman
      with a tumor of the upper pole of the right kidney invasive by the continuity of
      the right lobe of liver, in which the classic methods of obtaining hemostasis
      supplemented using Tachosil postoperative course and a comparison with data from
      the literature. RESULTS: We demonstrated the usefulness of the application
      Tachosil sealing vascular suture in the vein cava inferior and obtain hemostasis
      and tissue sealing the right liver lobe cross-section area of about 250 cm2.
      After treatment, a patient had drainage from the site of the kidney comparable
      with data from the literature. Patient was discharged home on postoperative day 7
      in good condition. CONCLUSIONS: Tachosil in major surgery because of locally
      advanced kidney cancer that invades the liver is a valuable complement to
      conventional surgical methods allowing for atraumatic stop bleeding and seal
      parenchymal liver tissue. Doing so helps to avoid early and late complications
      and reduce the cost of treating these complications.

PMID- 23882934
TI  - [The conversion of hypothyroidism into hyperthyroidism during leflunomide with
      povidone iodine treatment of rheumatoid arthritis].
AB  - Till now there has not been reported data related to the influence of leflunomide
      on the thyroid gland function of the treated person. The authors described the
      case of woman with rheumathoid arthritis and hypothyroidism who revealed
      hyperthyroidism in 7 months after starting leflunomide tablets treatment
      containing povidone iodine as well. Also both autonomical tissue area in thyroid
      right lobe and hight TSHRAb level were found. Leflunomid tablets containing
      povidone iodine in its structure can cause hyperthyroidism in the person with
      previous hypothyroidism and nodular goiter, probably as a result of immunological
      reconversion and tissue nodular functional autonomisation. In persons with
      nodular goitre one should prefer free of povidone iodine leflunomide treatment
      and also monitor serum thyroid hormone contents and thyroid antibodies as well.

PMID- 23882935
TI  - [Evaluate the effectiveness of laser therapy in the treatment of diabetic
      maculopathy].
AB  - Diabetes mellitus concerns a growing number of people in the world. Its
      complications are an important social problem. Diabetic macular edema (DME) is
      one of the leading causes of visual loss in the course of the disease.
      Deterioration of vision is typically the patients with long-standing, poorly
      controlled diabetes, both type 1 and 2. DME can occur at any stage of the
      disease. Because structural changes in the macula are reversible in the initial
      period, it is important to start treatment early. In the treatment of diabetic
      uses three techniques retinal laser--direct photocoagulation, photocoagulation a
      "grid" and the panphotocoagulation. The aim of this study was to evaluate the
      effectiveness of laser therapy in the treatment of diabetic macular edema.
      MATERIALS AND METHODS: The study included 90 patients (180 eyes) with DME, 50
      women and 40 men aged from 18 to 80 years with a visual acuity of 0.08 to 0.7
      with the best corrected on the Snellen chart. 9 people were with type 1 diabetes,
      81 with type 2. 86 patients applied insulin, 4 people took drugs. Eye with poor
      visual acuity was qualified for the treatment. In all patients enrolled in the
      study visual acuity, anterior segment of the eye in the slit lamp and fundus by
      indirect ophthalmoscopy with Volk 78D lens were evaluated. DME was diagnosed on
      the basis of the results of fluorescein angiography and optical coherence
      tomography. In the patients laser therapy was performed twice: on day 1 after
      qualification and four months later. Performed two types of laser: the focal
      photocoagulation and the type of "grid" depending on the severity of DME. Retinal
      photocoagulation was performed using a diode laser 810 nm Diode Laser Systems
      OcuLight SL and SLx Iris Medical Models. Patients were monitored at 4 and 8
      months after the laser therapy. The results were statistically analyzed. RESULTS:
      Duration of diabetes less than 10 years was in 67 patients, over 10 years in 23.
      In patients with diabetes under 10 years predominated limited type of macular
      edema (92.65%), in patients over 10--diffuse (72.73%). As a result of the
      treatment in 34 patients (37.8%) visual acuity was improved. 91.18% of them had
      limited macular edema. In 47 patients (52.2%) showed the stabilization of vision.
      These patients had also more limited type of edema (74.47%). In 9 patients (10%)
      visual impairment were observed and they were mostly patients with diffuse
      macular edema (66.67%). Average visual acuity in patients with limited macular
      edema before laser therapy was 0.37 +/- 0.18. In the four months after the laser
      treatment improved slightly (0.38 +/- .18). After 8 months of treatment the
      average visual acuity in this group remained at a level of 0.44 +/- 0.16. In
      patients with diffuse macular edema output type visual acuity was significantly
      lower and averaged only 0.16 +/- 0.1. In 4 months after the laser was found in
      this group decreased vision (Vo = 0.13 +/- 0.08). In 8 months after surgery
      visual acuity averaged 0.15 +/- 0.09. Average visual acuity before laser therapy
      in this group was 0.36 +/- 0.17, and 8 months after was at the level of 0.43 +/-
      0.16. In patients with diabetes more than 10 years laser therapy has not brought
      the desired effect, and visual acuity were as follows: before treatment--0.18 +/-
      0.16 and 8 months after--0.17 +/- 0.14 (p < 0.0001). Average macular thickness
      before laser therapy in patients with limited edema was 348.14 +/- 33.47 microns.
      In 4 months after the laser has been observed decreased to 340.29 +/- 31.2
      microns, and after 8 months of further withdrawal of edema to an average of
      337.88 +/- 32.95 microns. In patients with diffuse type average macular thickness
      was 394.38 +/- 38.18. After 4 months of laser treatment exacerbation of edema
      (mean 399 +/- 38.08). After 8 months, the thickness of macula in this group was
      average 388.95 +/- 32.85. CONCLUSIONS: Laser therapy is an effective type of
      treatment for DME. Better results after laser therapy are obtained in patients
      with a short-term macular edema and good visual acuity. In order to maintain
      useful visual acuity, patients with DME should undergo laser treatment in the
      early stages of the disease.

PMID- 23882936
TI  - [Pulmonary arterial hypertension: modern diagnostics and therapy--Part 1].
AB  - Pulmonary arterial hypertension (PAH) belongs to the group of rare diseases and
      the morbidity rate is 15 to 50 people per million per year. Before the era of
      specific treatment of PAH, the prognosis was poor. The average life expectancy of
      the patients was 2.8 years. However, in the last years there has been a
      breakthrough in treating the patients with PAH. The introduction of this specific
      treatment has prolonged the life and improved the quality of it within the group
      of the patients with PAH. In Poland, since 2008 the therapy has been organized by
      the Pulmonary Hypertension Therapeutic Program. PAH is a recognition done by
      excluding more probable causes of pulmonary hypertension (PH) such as: PH due to
      left heart disease and lung disease, chronic thromboembolic pulmonary
      hypertension (CTEPH) and PH with multifactorial mechanisms. The clinical symptoms
      of pulmonary hypertension are non-specific, they develop for a several months and
      they are mainly caused by progressive right ventricular failure. The base of PAH
      recognition is echocardiography, which indirectly estimates the pulmonary artery
      systolic pressure. However, the golden standard of PAH diagnostics is right heart
      catheterization (RHC) with measurements of pulmonary arterial pressure (PAP),
      right atrial pressure (RAP), right ventricular pressure and pulmonary wedge
      pressure (PWP). The early PAH recognition and the correct classification of
      patients to the treatment organized by the Pulmonary Hypertension Therapeutic
      Program give them a chance for longer and more comfortable life.

PMID- 23882937
TI  - [Briquet syndrome in patients with fibromyalgia].
AB  - Fibromyalgia is a disorder of the pain perception, which may, but need not be
      associated with depression. Modern science does not allow to put an equal sign
      between the two diseases. However, at least in some people, can be seen as a
      variant of depression, fibromyalgia. Studies indicate that 50-80 per cent, people
      with fibromyalgia can recognize depression. The article discusses the current
      state of knowledge on the role of physical activity, psychosomatic health
      treatments, physical therapy, relaxation techniques and education for patients
      with fibromyalgia. The best results, combine different therapies. The use of
      drugs is to reduce pain, improve mood and improve sleep quality. Various forms of
      drug-free treatment and help to restore the efficiency of dealing with
      complaints. In the treatment of fibromyalgia using different forms of therapy,
      tailored to the individual needs of the patient. The most common are:
      balneotherapy, exercise, cryotherapy, cognitive-behavioral psychotherapy and
      other forms of psychotherapy--in order to develop methods to combat stress and
      depressed mood, relaxation techniques, acupuncture, massage.

PMID- 23882938
TI  - [Health education from the perspective of contemporary challenges and threats].
AB  - The latest socio-economical changes have had a great impact on the perception of
      health issues. The definition of health according to the WHO is often citied here
      as a kind of postulate of psychical, psychological and sociological well being.
      Health education takes an important part in propagating ideas of promoting and
      protecting health and also shaping life skills. Health education especially
      affects schools but it also has an impact on family and local community.
      Contemporary definitions of health education underline that it is also a process
      of learning how to take care of one's own health and that of others'. This
      attitude to health corresponds with the changing health problems affecting
      society. Despite implementing many programs and actions promoting health and
      preventing diseases on a world and European scale, there still exist many
      problems in this area. They are particularly due to disproportionate access to
      medical help and technological development resulting from low awareness, but most
      of all, from the low socioeconomic status of the people involved. The school, as
      a place where health education takes place, has the right and obligation to
      influence health behaviors of pupils and the whole of society.

PMID- 23882939
TI  - [Does sunscreen use influence the level of vitamin D in the body?].
AB  - Solar radiation is necessary for the normal functioning of the body. It enables
      the synthesis of vitamin D that supports the physiological status of the
      skeleton, it also improves the frame of mind. Nevertheless, UV irradiation also
      induces adverse effects in the skin, including sunburn and skin cancer. The use
      of sunscreens is highly recommended during periods of intensive insolation. There
      are, however, concerns about possible interference with synthesis of vitamin D in
      the skin by sunscreens, which might lead to hypovitaminosis. The present article
      summarises published studies on the possible inhibition of vitamin D synthesis as
      a result from using sunscreens.

PMID- 23882940
TI  - [Comigration of root nodule bacteria and bean plants to new habitats: coevolution
      mechanisms and practical importance (review)].
AB  - The review summarizes the results of studies on the comigration of tubercular
      bacteria and bean plants to new habitats, which is often accompanied by a
      decrease in the symbiosis efficiency due to a loss of the diversity of genes
      responsible for the interaction. This migration may lead to a rise in new
      symbionts as a result of gene transfers from initial symbionts to local bacteria.
      It was demonstrated that typically new symbionts lack an ability for N2 fixation
      but are highly competitive, blocking the inoculation of bean cultures by
      industrial strains. The design of coadapted systems of recognition and signal
      interaction of partners is a perspective approach to ensure competitive
      advantages of efficient rhizobia strains introduced into agrocenoses, together
      with host plants, over inactive local strains.

PMID- 23882941
TI  - [Influence of rhizobial (Rhizobium leguminosarum) inoculation and calcium ions on
      the NADPH oxidase activity in roots of etiolated pea (Pisum sativum L.)
      seedlings].
AB  - Changes in the functional activity of the NADPH oxidase in the microsomal
      fraction of roots of etiolated pea seedlings, caused by rhizobial inoculation and
      calcium ions (Ca2+), are shown. The enzyme activity in a medium with an exogenous
      source of Ca2+ (CaCl2, 100 microM) fluctuated, increasing 5 to 20 min and
      decreasing 10 and 30 min after addition. A calcium chelator (ethylene glycol
      tetraacetic acid (EDTA), 100 microM) potentiated the decrease in the enzyme
      activity in the presence of exogenous calcium. Rhizobial inoculation caused a 3.9
      fold increase in the enzyme activity 5 min after inoculation compared to the
      control (without inoculation). The Ca(2+)-channel activator (amiodarone, 300
      microM) and the Ca(2+)-channel blocker (lanthanum chloride, 400 microM) reduced
      the NADPH oxidase activity after rhizobial inoculation compared to the control
      level (without inoculation). It is concluded that Ca2+ and reactive oxygen
      species are involved in the regulation of the membrane NADPH oxidase activity in
      roots of pea seedlings.

PMID- 23882942
TI  - [Production of modified magnetosome membrane proteins and analysis of their
      activity].
AB  - Genetic constructs coding for the fusion of the Mam12 membrane protein from the
      magnetotactic bacteria Magnetospirilium magnetotacticum with one B-domain (mb) or
      two B or Z domains (mbb and mzz, respectively) of Staphylococcus aureus protein A
      have been synthesized. Expression, fractionation, and purification of fusion
      proteins have been performed, and the activity of the modified proteins has been
      characterized. ELISA results showed that all modified proteins displayed
      immunoglobulin-binding activity.

PMID- 23882943
TI  - Purification and characterization of nitroreductase from red alkaliphilic
      bacterium Aquiflexum sp. DL6.
AB  - Nitroaromatic compounds are toxic to living organisms. Most of them exhibit human
      mutagenic and carcinogenic potential. Biotransformation and bioremediation
      processes can convert these compounds into non-toxic compounds. Acclimatization
      of bacterial strain Aquiflexum sp. DL6 with nitro-aromatics resulted in
      significant induction of nitroreductase (EC 1.5.1.34). The enzyme was purified by
      the combination of DEAE-cellulose and Sephadex G-100 column chromatography with
      80-fold purification and 22% yield. Molecular weight of purified nitroreductase
      was estimated to be 29 kDa by SDS-PAGE. The enzyme characteristics were explored
      by varying the pH and temperatures, and the optimum activity was found at pH 9.5
      and 40 degrees C. It was revealed that the substrate specificity of
      nitroreductase of Aquiflexum sp. DL6 was wide for the most of the tested nitro
      aromatic compounds. The kinetic parameters like Michaelis constant and velocity
      maxima were determined with o-nitrophenol and NADH as substrates.

PMID- 23882944
TI  - [Microbiological synthesis of [2H]-inosine with a high degree of isotopic
      enrichment by the gram-positive chemoheterotrophic bacterium Bacillus subtilis].
AB  - A 2H-labeled purine ribonucleoside inosine was microbiologically synthesized
      (yield, 3.9 g/L of culture liquid) using a deuterium-adapted strain ofthe gram
      positive chemoheterotrophic bacterium Bacillus subtilis, cultivated in a heavy
      water medium with a high degree of deuteration (99.8 at % 2H) containing 2%
      hydrolysate of deuterated biomass of the methylotrophic bacterium Brevibacterium
      methylicum as a source of 2H-labeled growth substrate produced in an M9 minimal
      medium with 98% 2H20 and 2% [2H]-methanol. The inosine extracted from the culture
      liquid of the producer strain was fractionated by adsorption (desorption) on an
      activated carbon surface, extraction with 0.3 M ammonium-formate buffer (pH 8.9),
      subsequent crystallization in 80% ethanol, and ion exchange chromatography on a
      column with AG50WX 4 cation exchange resin equilibrated with 0.3 M ammonium
      formate buffer containing 0.045 M NH4Cl. Fast atom bombardment (FAB) mass
      spectrometry demonstrated incorporation of five deuterium atoms in the inosine
      molecule (62.5% 2H), three of which were contained in the ribose moiety and two
      in the hypoxanthine moiety.

PMID- 23882945
TI  - [Destruction of aromatic hydrocarbons by the Rhodococcus wratislaviensis KT112-7
      strain isolated from waste products of a salt-mining factory].
AB  - The destruction of aromatic hydrocarbons by the Rhodococcus wratislaviensis KT112
      7 strain isolated from technogenic mineral waste products of the BKRU1 Uralkalii
      factory has been investigated (city of Berezniki, Perm krai). The R.
      wratislaviensis KT112-7 was shown to utilize increased concentrations of
      ophthalic (o-PA) (8 g/L) and benzoic (BA) (3.4 g/L) acids. The strain grows with
      o-FA, BA, and biphenyl at a NaCl content of up to 50, 90, and 75 g/L in the
      culture medium, respectively. Based on an analysis of the metabolic profile and
      nucleotide sequences of the bphA1, benA, and phtB genes, the KT112-7 strain was
      established to decompose o-PA via the formation of 3,4-dihydroxyphthalic and 3,4
      dihydroxybenzoic acids. The decomposition of biphenyl is carried out via the
      formation of BA and then at low concentrations of NaCl (up to 50 g/L) via the
      formation of 4-hydroxybenzoic acid followed by its oxidation; at high
      concentrations of NaCl (over 60 g/L), via the direct oxidation of benzoic acid
      with the production of catechol. These data indicate that the Rhodococcus
      wratislaviensis KT112-7 destructor strain is a promising strain for the
      development of new biotechnologies directed at the utilization (transformation)
      of aromatic compounds, including under the conditions of increased
      mineralization.

PMID- 23882946
TI  - Metal solubilization from powdered printed circuit boards by microbial consortium
      from bauxite and pyrite ores.
AB  - With the current rapid developments in technology, there is an increasing
      accumulation of outdated electronic equipment. The primary reason for this
      increase is the low rate of recycling due to the complex nature of such waste.
      Bioleaching offers a promising solution for this problem. Study was conducted on
      the solubilization of heavy metals from electronic waste (e-waste). For this
      purpose, a microbial consortium from bauxite and pyrite ore samples was obtained
      using a simple "top down" approach. Essentially, printed circuit boards (PCB)
      were obtained and used as representative samples of e-waste. Various
      concentrations (1-5%) of PCB powder were subjected to bioleaching, and the
      effects on metal solubilization, changes in pH and concentration of ferrous iron
      produced were assessed. It was observed that a maximum of 96.93% Cu and 93.33% Zn
      was solubilized by microbial consortium from 10 g/l of PCB powder, whereas only
      10.26% Ni was solubilized from 30 g/l of PCB powder. For lead, only 0.58%
      solubilization was achieved from 20 g/l of PCB powder. An analysis of the
      precipitate formed during bioleaching using scanning electron microscopy with
      energy dispersive x-ray analysis revealed the presence of Tin (59.96%), Cu
      (23.97%), Pb (9.30%) and Fe (5.92%).

PMID- 23882947
TI  - [Identification of genes encoding ligninolytic enzymes in naturally occurring
      basidiomycete isolates].
AB  - The presence of genes encoding lignin peroxidase, laccase, and manganese
      peroxidase was assessed in more than 20 types of polypore fungi collected in the
      woods of Kirov oblast; the fungi studied had not been previously characterized
      with regard to ligninolytic enzyme production. Fifteen isolates of eleven
      basidiomycete species were shown to contain genes coding for all three
      ligninolytic enzymes. Genes coding for these enzymes were detected in D. mollis,
      D. quercina, F. pinicola, G. trabeum, G. lucidum, H. fasciculare, L. betulina, P.
      betulinus, P. igniarus, P. pomaceus, P. pini, and P. cinnabarinus for the first
      time.

PMID- 23882948
TI  - [Transformation of humic substances of highly oxidized brown coal by the
      basidiomycetes fungi Trametes hirsuta and Trametes maxima].
AB  - The ability of the white rot basidiomycetes Trametes hirsuta and Trametes maxima
      to transform coal humic substances (HS's) under the conditions of solid phase
      cultivation in the presence or absence of an easily available source of corbon
      (glucose) has been studied. It was shown that during the growth of the fungal
      strains used in media, containing HS's, destructive and condensation processes of
      HS transformation proceeded simultaneously. Based on a comparative
      physicochemical analysis of the initial HS's and HS's transformed by the fungi,
      it was established that, despite the introduction of glucose may favor a deeper
      transformation of HS's by basidiomycetes, the general direction of their
      modification is dominant reduction or oxidation and is determined by the
      physiological biochemical peculiarities of the strain used.

PMID- 23882949
TI  - [Recombinant strain producing thermostable lipase from Thermomyces lanuginosus
      immobilized into nanocarbon silica matrices and properties of the prepared
      biocatalyzers].
AB  - Multicomponent composite biocatalyzers with lipolytic activity have been studied.
      These biocatalyzers were prepared through the immobilization of a recombinant
      producer strain of thermostable lipase from Thermomyces lanuginosus into SiO2
      xerogel, which contains a nanocarbon component, i.e., multilayered carbon
      nanotubes with varying diameters, and also bulblike structured carbon nanospheres
      ("nanobulb"). The properties of lipase were studied both in cell suspensions of a
      recombinant producer strain constructed based on E. coli BL21(DE3) and in the
      immobilized state with regard to the structure and dispersibility of the
      nanocarbon component used in the composition of the biocatalyzers. It was shown
      that the recombinant intracellular lipase exerted its activity in a reaction of
      tributirin hydrolysis on average comprising 50 U/mg of dried cells and had a high
      level of thermostability. Upon heating in olive oil at 100 degrees C, the
      inactivation constant and the period of semi-inactivation comprised 6 x 10(-3)
      min(-1) and 2 h, respectively, exceeding by one order the thermostability of
      lipase in a buffer solution. Biocatalyzers that contained aggregated "thick"
      nanotubes with a diameter of 20-22 nm had the maximum initial activity-250 U/g.

PMID- 23882950
TI  - [Detection of pyrethroids by spectral correlation interferometry].
AB  - A label-free method based on spectral correlation interferometry has been
      developed for highly sensitive detection of pyrethroids by competitive
      immunoassay on the surface of sensor chips made of widely available microscopy
      glass cover slips. It is shown that the method allows independent optimization of
      each step of the sensor surface modification. This fact may be used to increase
      the efficiency of development of protocols for a wide spectrum of immunoassays
      that employ glass surface as a solid phase. Detection of 3-phenoxybenzoic acid,
      which is one of the most stable metabolites of a large number of pyrethroids, on
      the surface of the optimized sensor chips has been demonstrated on the level of
      15 pg/ml. That is 50 times better than the sensitivity of the enzyme-linked
      immunosorbent assay (ELISA).

PMID- 23882951
TI  - [Thromboresistance of glucose-containing hydrogels].
AB  - The thromboresistance of glucose-sensitive polymer hydrogels, modeling one of the
      functions of the pancreas, namely, the ability to secrete insulin in response to
      the introduction of glucose into the environment, has been studied. Hydrogels
      were synthesized by the copolymerization of hydroxyethyl methacrylate with N
      acryloyl glucosamine in the presence of a cross-linking agent and subsequently
      treated with concanavalin A. Introduction of glucose residues into the hydrogel
      did not result in significant changes in either the number of trombocytes adhered
      to the hydrogel or the degree of denaturation of blood plasma proteins
      interacting with the hydrogel. Consequently, the biological activity of insulin
      did not change after release from the hydrogel. The use of glucose-sensitive
      hydrogels is supposed to contribute to the development of a novel strategy for
      the treatment of diabetes.

PMID- 23882952
TI  - [Enzyme immunoassay of usnic acid in lichens].
AB  - An enzyme immunoassay for usnic acid in lichens was developed, the sensitivity of
      which was 0.1 microg/g of air-dried material (0.00001%). Polyclonal rabbit
      antibodies against bovine serum albumin conjugated to (+)-usnic acid under the
      conditions of formaldehyde condensation made it possible to determine the
      analyzed substance in solutions at concentrations from 1 ng/mL when it interacts
      with an immobilized gelatin conjugate homologous in the binding mode. Usnic acid
      in 2-26600 microg/g (0.0002-2.6%) amounts was found in all 236 studied samples of
      lichens belonging to 53 species and 8 families.

PMID- 23882953
TI  - Universal health coverage.

PMID- 23882954
TI  - Factors affecting the prevalence of chronic diseases in Palestinian people: an
      analysis of data from the Palestinian Central Bureau of Statistics.
AB  - This study determined whether there are significant differences in the prevalence
      of diabetes, hypertension, cardiovascular disease (CVD) and cancer among
      Palestinians with respect to different demographic variables using secondary data
      from the Palestinian Central Bureau of Statistics. Living in the Gaza Strip was a
      protective factor, with this group being 21% less likely to have diabetes, 35%
      less likely to have hypertension, and 48% less likely to have CVD than those
      living in the West Bank. No significant difference was found for cancer. Being a
      refugee was a significant risk factor for diabetes and CVD while being
      married/engaged or divorced/ separated/widowed was a risk factor for diabetes and
      hypertension. Gender was a risk factor for hypertension with females being 60%
      more likely to have hypertension than males. Living in a rural setting was
      protective against hypertension. As expected, age was a risk factor for diabetes,
      hypertension and CVD; the magnitude of this increased risk was alarming, 36 to
      434 times greater in those aged 40-65 years compared with those aged 0-19 years.

PMID- 23882955
TI  - WHO MPOWER tobacco control scores in the Eastern Mediterranean countries based on
      the 2011 report.
AB  - The aim of this cross-sectional study was to quantify the implementation of
      MPOWER tobacco control policies among Eastern Mediterranean Region countries.
      Information was obtained from the 2011 WHO MPOWER report. A checklist was
      designed and its scoring was agreed by Iranian and international tobacco control
      specialists. Seven questions were scored from 0-4 and 3 from 0-3. The 22
      countries were ranked by their total score on a scale of 0 to 37. The highest
      scores were achieved by the Islamic Republic of Iran, Egypt and Jordan 29, 28 and
      26 respectively. Twelve of the countries (55%) scored more than half of the
      possible score (19). The lowest and highest scores for all countries summed were
      on sections related to banning smoking in public places (18) and tobacco
      advertising bans (66) respectively. Compliance with smoke-free policies was
      especially low. MPOWER programmes are accepted in the Region but there is
      considerable room for improvement. Input from countries based on their successes
      and challenges is needed to strengthen the programmes.

PMID- 23882956
TI  - Geographic epidemiology in a small area: cancer incidence in Baakline, Lebanon,
      2000-2008.
AB  - Aggregate data of the National Clr cac gi s in Lebanon cannot discriminate cance
      r incidence i n small areas. Trained community members surveyed the permanent
      population of the Baakline municipality using the verbal autopsy approach. We
      surveyed 1042 households with at least 1 member living permanently in Baakline
      during 2000-2008. Data covered 4330 persons yielding 34,143 years of observation
      and 56 new cases of cancer were reported. Median age at diagnosis varied
      significantly between men (77 years) and women (56 years). The most common types
      were lung cancer (20%) followed by colorectal (12.5%) and breast (9%). Estimated
      crude cancer incidence rate was 164 cases/100,000 persons/year, significantly
      higher in men (194) than women (130), and much lower overall than the national
      figure (218). The permanent Baakline population is older than that of Lebanon
      itself, yet the cancer incidence rate is markedly lower than the national figure.
      This finding pleads for serious efforts to preserve the low environmental
      contamination and the healthy lifestyles in food and tobacco abstinence that have
      protected the population so far.

PMID- 23882957
TI  - Antenatal depression and its predictors in Lahore, Pakistan.
AB  - Mental health is an important but neglected component of reproductive health.
      This study aimed to determine the prevalence and risk factors for antenatal
      depression among women attending for antenatal care at an urban tertiary care
      hospital in Lahore, Pakistan. In a cross-sectional study, structured
      questionnaires were filled and screening for depression was done using the
      Edinburgh postnatal depression scale (EPDS). Out of 506 antenatal attendees 126
      (24.9%) had no depression (EPDS scores<10), 53 (10.5%) scored 10-12 and 327
      (64.6%) had EPDS scores>12. Depression scores (>or=10) were more common in
      mothers aged<20 years (93.7%) than those aged>35 years (55.0%). Fear of
      childbirth and separation from husband were identified as significant risk
      factors for development of antenatal depression, while family history of
      psychiatric illness was significant protective factor. Domestic violence, drug
      abuse, lack of support, previous miscarriage and personal history of previous
      psychiatric illness were not found to be significant risk factors.

PMID- 23882958
TI  - Physical abuse in basic-education schools in Aden governorate, Yemen: a cross
      sectional study.
AB  - Physical abuse in school has lifelong consequences affecting child health and
      educational achievements. A study was designed to assess the prevalence of
      physical abuse experienced by pupils in basic-education schools in Aden, Yemen,
      and to examine the risk factors associated with it. A cross-sectional study
      covering 1066 pupils in 7th-9th grades from 8 schools in different districts of
      Aden governorate were randomly selected. Answering an anonymous self-administered
      questionnaire, 55.7% of pupils reported physical abuse at least once in their
      school lifetime (73.2% of males versus 26.6% of females). Teachers were the main
      perpetrators (45.4%). A statistically significant association was found between
      physical abuse and sex, age group, family type and father's education.
      Significant predictors of physical abuse on multivariate regression were male sex
      (OR=7.89) and extended family type (OR=1.36). Physical abuse in basic-education
      schools requires serious consideration by educational authorities, families and
      the community at large.

PMID- 23882959
TI  - Do personal beliefs and peers affect the practice of alcohol consumption in
      university students in Lebanon?
AB  - Alcohol consumption is frequent among university students in Lebanon as elsewhere
      in the world. A cross-sectional study was conducted in Lebanon's public and
      private universities between October 2009 and September 2010 using a standardized
      questionnaire to assess personal beliefs about alcohol consumption, peers'
      behaviours and opinions and history of and current drinking practices. Of 1235
      students, 199 (16.1%) had an AUDIT score>or=8. Older age, male sex, Christian
      religion, attending a private university, studying a non-health specialty and
      residing in Beirut or Mount Lebanon were associated with a higher risk of harmful
      drinking. Beliefs concerning alcohol consumption and peers' opinions and
      behaviours were factors significantly associated with harmful drinking,
      especially: ignoring the dangers of alcohol consumption; higher frequency of
      consumption with friends; and a higher proportion of friends who drank regularly.
      University students' alcohol drinking behaviour was mostly influenced by peers'
      behaviour, and a peer education programme is recommended to decrease the risk of
      harmful drinking.

PMID- 23882960
TI  - Factors influencing women's willingness to volunteer in the healthcare system:
      evidence from the Islamic Republic of Iran.
AB  - This case-control study evaluated the factors influencing volunteering in the
      Islamic Republic of Iran's Women's Health Volunteer (WHV) programme, which is
      implemented in 150 centres in Khorasan-e-Razavi Province. We recruited 145 cases
      (volunteers) and 146 controls (non-volunteers) from the centres. Data were
      collected by questionnaire. Sociodemographic variables included were: length of
      residence in neighbourhood, number of siblings, husband's age and education and
      job, family size, quality of life, self-rated health status, neighbourhood
      intimacy, child under 2 years, house ownership, wealth index. Social network
      variables included were: ego network size, type of acquaintance, intimacy with
      others, relationship communication, relationship duration, emotional support,
      advisory support, monetary support, physical support, time support. There were
      significant associations (P<0.05) between women's propensity to volunteer and
      family size, presence of a child under 2 years in the family, neighbourhood
      intimacy, social network composition, and emotional and advisory support.

PMID- 23882961
TI  - Characterization of wound infections among patients injured during the 2011
      Libyan conflict.
AB  - Few studies have analysed the bacterial pathogenesis of infections associated
      with war-wound in the Eastern Mediterranean region. We analysed surgical wound
      infections of 1200 patients injured during the Libyan conflict in 2011 and
      admitted to the emergency services at Tripoli medical centre. Culture swabs or
      surgical wound debridement samples were collected and cultures were identified
      and tested for antimicrobial resistance. Of the 1200 patients studied, 498 (42%)
      were infected with at least 1 pathogen and 57 with >2 pathogens. The most common
      species were Acinetobacter spp. (isolated from 144 patients), coagulase-negative
      staphylococci (122), Escherichia coli (107), Pseudomnonas aeruginosa (92) and
      Klebsiella spp. (86). A high level of resistance to the antibiotics tested was
      found, especially among Acinetobacter spp. Multi-drug-resistant Gram-negative
      bacilli were an important complicating factor in wound infections associated with
      war injuries among injured patients in Libya. Effective policies are needed to
      control and treat such infections particularly in trauma and emergency services.

PMID- 23882962
TI  - Relation between some haematological abnormalities, degree of immunosuppression
      and viral load in treatment-naive HIV-infected patients.
AB  - This cross-sectional study at a teaching hospital in north-eastern Nigeria
      estimated the prevalence of anaemia, leukopenia and thrombocytopenia in treatment
      naive HIV-infected patients (177 males and 316 females), and the associations
      with virological and immunological markers. The overall prevalences of anaemia,
      leukopenia and thrombocytopenia were 49.5%, 5.5% and 4.5% respectively. The
      prevalence of anaemia was significantly higher in males than females (61.6%
      versus 42.7%), while the rates of leukopenia (5.1% versus 5.7%) and
      thrombocytopenia (5.7% versus 3.8%) were similar. Almost two-thirds of the HIV
      treatment-naive studied patients, 293/493 (59.4%), had cytopenia and would
      require antiretroviral drugs. AIDS was diagnosed by clinical or immunological
      criteria in 70% of patients. The degree of cytopenia was directly related to the
      degree of immunosuppression and clinical AIDS status. No relationship was
      observed between cytopenia and viral load.

PMID- 23882963
TI  - Study of methacholine positivity in patients with chronic cough at Masih
      Daneshvari hospital, Tehran, 2007-2008.
AB  - While airways reactivity is among the characteristics of asthma, it is not
      considered a sufficient condition diagnostically and the methacholine challenge
      is a non-specific diagnostic aid in cases of chronic cough and reactive airways
      disease. The aim of this cross-sectional study was to determine the metacholine
      response positivity and diagnosis of asthma in patients with chronic cough
      presenting to a hospital in Tehran during 2007 and 2008. Of 101 patients with
      chronic cough (with no history of sinusitis, recent pulmonary infection,
      bronchitis, gasteroesophageal reflux or underlying pulmonary conditions), 51.5%
      showed reactive airways disease to the methacholine test, 40.6% were unreactive
      and 7.9% were indeterminate. A positive methacholine challenge test was
      positively correlated with new wheezing. Although the methacholine challenge test
      is not a primary test for evaluating chronic cough, if no other reason for
      chronic cough is found, it may be a guiding test for asthma.

PMID- 23882964
TI  - Renal patients' views on generic prescribing and substitution: example from the
      United Arab Emirates.
AB  - This survey examined current patient awareness and understanding of generic
      substitution. We surveyed 188 renal patients using 36 multiple-choice questions
      in 2 hospitals in the United Arab Emirates. We found that 70% of patients were
      aware of the availability of generic medicines, 60% understood the terms
      "generic" and "branded" in relation to medicines and 64% were conscious of
      generic substitution practice. However, 32% did not know if they were taking
      generics and 31% felt that generics were not equivalent or only sometimes
      equivalent to branded medicines. Nearly half (47%) the patients stated they would
      refuse generic substitution of ciclosporin when it became available if this was
      just to save the health authority money. In our opinion, random generic
      substitution should not be implemented because there is still uncertainty and
      lack of knowledge among patients.

PMID- 23882965
TI  - Demographics and the social reckoning in the Arab region.
AB  - Demographic transitions in the Arab countries, due to declining birth rates and
      mortality rates since the 1980s, are reflected in a low proportion of children, a
      relatively stable proportion of elderly and a high proportion of people of
      working age. This "youth bulge" of young, active, working-age individuals in the
      current population may open a demographic window for countries to benefit from
      increased savings and investment. This paper reviews the demographic situation in
      the Arab region and the impact of education, employment, migration, health status
      and participation in society on the further development of the region, including
      the impact of these factors on ageing and gender issues. The intent is to draw
      attention to the importance of these demographic changes and highlight the need
      for action to maximize the potential benefit to the population in this region.

PMID- 23882966
TI  - Consensus recommendation for meningococcal disease prevention for Hajj and Umra
      pilgrimage/travel medicine.
AB  - The Islamic Hajj to Makkah (Mecca) has been associated with outbreaks of invasive
      meningococcal disease and the global spread of Neisseria meningitidis serogroup W
      135. For Hajj pilgrims the quadrivalent vaccination against serogroups A, C, W
      135 and Y is a mandatory requirement. Novel conjugate vaccines may provide
      benefits for the community by reduction of carriage. With the introduction of the
      new generation of quadrivalent meningococcal conjugate vaccines (Menveo,
      Menactra, and others pending license) and their recent implementation in Saudi
      Arabia, experts from 11 countries in the Middle East region met at a
      Meningococcal Leadership Forum (MLF), in Dubai in May 2010 to exchange opinions
      on meningococcal disease and prevention strategies. These experts discussed the
      importance of introducing conjugate vaccines for pilgrims and travellers, and
      elaborated a consensus recommendation to support healthcare professionals and
      decision-makers.

PMID- 23882967
TI  - A case of vocal tic: an unusual presentation of neurobrucellosis.

PMID- 23882968
TI  - Pediatric hematopoietic stem cell transplantation: fifteen year experience in
      Puerto Rico.
AB  - This study summarizes the development and progress of the pediatric Hematopoietic
      Stem Cell Transplantation (HSCT) program in Puerto Rico. Data from the two
      pediatric transplant centers was collected from July 1994 through December 2009.
      Overall, in the last 15 years 97 transplants have been performed to 87 children
      and young adults. These included 55 males and 32 females, aged between 1 and 38
      years of age. The diagnosis included: acute leukemia, chronic leukemia,
      myelodysplasia, aplastic anemia, histiocytosis, neuroblastoma, lymphomas, PNET,
      Wilms tumor, and desmoplastic round cell tumor. Sources of hematopoietic stem
      cells for transplantation included: 5 autologous bone marrow, 23 allogeneic bone
      marrow using HLA matched sibling; 18 allogeneic peripheral blood stem cell (PBSC)
      using HLA-matched sibling and one syngeneic PBSC; 4 haploidentical T-cell
      depleted bone marrow transplant and 47 autologous PBSC. The results in the past
      15 years are encouraging and conform that HSCT is a valuable treatment option in
      our pediatric population to no other alternative therapy. Our experience compares
      to those published by others with a 15-year overall survival of 48%. In this same
      group, the transplant related mortality was 14.9% comparable to published
      experience in Europe and USA.

PMID- 23882969
TI  - Relation between serum vitamin D level and asthma.
AB  - Asthma is a chronic multifactorial condition racterized by inflammation,
      bronchial hyperresponsiveness, narrowing of airway associated with wheezing and
      shortness of breath, where trials have evidenced that approximately 50% despite
      being on adequate treatment don't achieve optimal control. Asthma has been
      related to vitamin D deficiency, where lower levels have been correlated to an
      increased hyperreactiveness and lower measures in pulmonary function test. Up to
      our knowledge, no studies have been conducted in Hispanic patients for this
      association. METHODS: Cross-Sectional pilot study in the setting of a pneumology
      office practice. Population consisted of asthmatic patients with no past medical
      history or risk factors for lower vitamin D levels. Variables studied included
      Peak-Flow s a measurement of the maximal velocity of air expelled in a forced
      exhalation adjusted for height and age; Serum vitamin D levels where optimal was
      > 30, and deficient < 30. Data coIlection period occurred between January 2010
      and May 2011. RESULTS: A direct proportion relation between vitamin D levels and
      asthma control test (ACT) questionnaire was noted. An inversely direct proportion
      between vitamin D and peak flow was evidenced, while no relation noted between
      peak flow and asthma. DISCUSSION: An 80% prevalence of vitamin D deficiency was
      noted in our population. Higher levels of vitamin D were associated with higher
      punctuation on ACT questionnaire, evidencing that most patients felt better
      during the last month. Peak flow measurements resulted to be lower when vitamin D
      was higher, though this measure could be influenced by a variety of external
      conditions.

PMID- 23882970
TI  - Osteoporosis in celiac disease: a Hispanic pilot study.
AB  - Osteoporosis has become an issue of worldwide significance. This condition has
      been demonstrated in Celiac disease (CD) populations in Europe, South America and
      the United States. However, data from the Hispanic population is limited.
      METHODS: Record review containing patients with Celiac disease in a
      Gastroenterology Clinic to evaluate the association of decreased bone density
      such as Osteoporosis and Osteopenia in subjects with Celiac disease in the
      southern population of Puerto Rico. We compared the results of Dual-energy X-ray
      absorptiometry. Clinical manifestations of CD in Hispanic population are
      described. RESULTS: Celiac disease data was available for seven patients; of
      those 6 were female (86%). The average age was 46 yr Most patients were
      overweight with a body mass index value of 29. CD patients showed abnormalities
      in hemoglobin, TSH and 25-Hydroxyvitamin D. The screening markers for CD showed a
      high value on IgA. The data to excel is the association of IgA vs. TSH showing
      strength of 90%. There was significantly lower bone density in women with Celiac
      Disease accounting for 86% of the cases. CONCLUSION: Women with Celiac Disease
      were associated with lower bone density and a higher prevalence of Osteopenia but
      not Osteoporosis.

PMID- 23882971
TI  - Nephropathy induced by contrast medium in an hispanic population after coronary
      angiography.
AB  - Contrast medium-induced nephropathy (CIN) is regarded as one of the most
      important complications after intravascular administration of radiographic
      contrast media and the third most common cause of hospital-acquired acute kidney
      injury. Contrast-induced nephropathy may develop in up to10% of patient with
      normal renal function but may be as high 25% in patient with risk factors.
      METHODS: A total of 192 medical records were obtained, in which 55 patient were
      eligible by our inclusion and exclusion criteria. RESULTS: A total four cases of
      CIN (7%) was identified and all were considered high-risk patients. In the
      patients that developed CIN only 50% received preventive IV hydration therapy in
      accordance to guidelines of the Contrast-Induced Nephropathy Consensus Panel. In
      51 cases CIN was absent (93%). In the absent CIN group 22 were considered high
      risk patients (43%) and 29 patients were low risk (57%). In the high-risk group
      with absent CIN, 77% received preventive IV hydration. CONCLUSION: Study didn't
      show diabetes as a direct contributory factor for CIN development, but glycemia
      was not properly stratified. Screening and preventive strategies were not
      diligently complied in our institution, so there is a great need to incorporate a
      protocol in our institution in accordance to published guidelines.

PMID- 23882972
TI  - Rheumatoid arthritis and anemia: the impact of different anti-inflammatory
      therapies on hemoglobin levels. An observational study.
AB  - Rheumatoid Arthritis (RA) has been associated with anemia. The treatment of
      anemia in RA includes blood transfusions, erythropoietic agents and iron
      supplements. Our observations suggest that the treatment of the inflammatory
      disease is associated with an improvement of hemoglobin (Hgb) levels in RA
      patients. METHODS: Record review, analyzing anemic RA patients and hemoglobin
      level changes after intensification of RA therapy. Three initial regimes were
      identified: corticosteroid (Prednisone), Disease Modifying Anti-rheumatic Drugs
      (DMARD's) plus Prednisone and for patients with no initial treatment with the
      initiation of Prednisone and or TNF a inhibitors (Etanercept). RESULTS: 8 female
      and 2 male patients with average age 59.7 + 14 years were selected. The results
      for the group treated with Prednisone initially N=4; showed a 0.9 g/dL increase
      in Hgb and Hct increase of 3% after addition of Etanercept. Those with DMARDs and
      corticosteroid regime had an Hgb and Hct increase of 1.2 g/dL and 3.5% after
      addition of Etanercept. The group with no initial treatment was further divided
      in two groups. The first was treated with Etanercept and the second was treated
      with Prednisone, resulting in average Hgb increases of 1.9 g/dl Hgb and 1.8 g/dL,
      and HCT increase 4% and 3.9% respectively. The global average change in Hgb was
      1.3g/dL and HCT increase 3.2%. CONCLUSION: The intensity of treatment of RA
      including Etanercept and Prednisone improved cases of mild anemia in rheumatoid
      arthritis.

PMID- 23882973
TI  - The epidiemiologic profile of HCV infected Hispanic patients from the southern
      area of Puerto Rico since 2005.
AB  - Seroprevalence studies in adults done in San Juan and Puerto Rico have showed
      6.3% and 2.2% of the population respectively, are positive for antibodies to
      Hepatitis C Virus (anti-HCV). It is been suggested that Hispanics have a lower
      sustained virological response to current therapy. The epidemiologic profile, the
      response to treatment and the risk factors to the poor response to treatment of
      HCV patients have not been studied in the southern area of Puerto Rico. METHODS:
      This is a cross-sectional analysis of data from 46 medical records from January
      2005 to March 2011. We search for sociodemographic variables, comorbidities, the
      HCV genotype, the human immunodeficiency virus profile, history of alcoholism and
      the patients who were treated with peginterferon alpha 2b and ribavirin, and
      their response to treatment. RESULTS: Our HCV infected population is male
      predominant (63%), and the most common route of transmission were intravenous
      drug abuse (37%) and blood transfusions (33%). Only 37% reported alcoholism. The
      most common comorbidities found in our population were hypertension (35%),
      diabetes mellitus (20%), hypothyroidism (7%) and dyslipidemia (7%). Most common
      genotype found in our population was type 1 (61%). From the 46 patients, 10
      patients were treated, being genotype 1 the most common. DISCUSSION: Overall, our
      population showed an epidemiological profile similar to other Hispanic groups in
      the literature, which should motivate us to continue exploring these
      associations, in an effort to improve the management of these patients.

PMID- 23882974
TI  - Renal biopsies in Puerto Rico patients with lupus nephritis.
AB  - The purpose of was to evaluate the renal pathology findings as described by the
      World Health Organization classification for systemic lupus erythematosus (SLE)
      in a group of Puerto Rico patients with lupus nephritis and determine the
      association with clinical and laboratory findings. The medical records from
      patients seen at the Lu pus Clinic from 1985 to 2005 were reviewed and patients
      with a performed renal biopsy included. All patients fulfilled the American
      ColIege of Rheumatology criteria for SLE. Data gathered from the medical records
      included demographics, cumulative clinical manifestations and serologic tests at
      the time of the renal biopsy. There were 139 patients with lupus nephntis (LN)
      and 71 patients (51%) had a renal biopsy done. From these 86% were females and
      their mean age at LN diagnosis was 25 years. The mean time between diagnosis of
      LN and renal biopsy was 1.5 years. The most frequent renal pathology was
      membranous glomewlonephritis (GN) class V (37%) followed by mesangial GN class II
      (23%). All groups were similar in clinical manifestations and laboratory
      parameters. The majority of Puerto Rico patients with LN had membranous GN class
      V. This data is different from other ethnic groups were diffuse GN type IV has
      been described as most prevalent.

PMID- 23882975
TI  - [Alzheimer-type dementia in a sample of Puerto Rican elderly: pilot study on the
      usefulness and assessment of a screening battery].
AB  - Dementia is one of the most prevalent conditions in the elderly. Dementia is
      defined as a decrease in memory, thinking and reasoning having its most common
      form as Alzheimer dementia. Alzheimer dementia (AD) economic cost to society is
      around 100 billion dollars annually. Unfortunately, at this point Puerto Rico,
      have neuro-psychopathology instruments limitations to perform valid and sensitive
      screening of DA. This study was directed to evaluate a battery of
      neuropsychological screening instruments for Puerto Rican elderly (60 to 100
      years, n = 50) with Alzheimer's dementia. In addition, calculate the sensitivity
      and specificity of the instruments. The tests where composed as screening battery
      and included CERAD (Instruments created by the Consortium to Establish a Registry
      for Alzheimer's Disease), MMSE (Mini mental Status Evaluation), EIWA-III
      (specifically the digit retention and similarities subtest that try to evaluated
      memory, concentration and abstract thinking) and the Tuokkos' test (clock drawing
      in order to evaluated visual-constructional skills). As show by ROC Curve
      (Receiver Operating Characteristic Curve) for our research, the sensitivity for
      CERAD was 95.7% with an specificity of 49%; MMSE (Mini Mental Status Evaluation)
      account for 89 sensitivity and 60% specificity; EIWA-III and subtest
      (specifically the digit retention and similarities subtest) respectively was
      80.4% sensitivity and 44.7% specificity; and sensitivity of 82.6% and specificity
      of 44.7%. Tuokkos' Clock Test accounted for 76.1% sensitivity, and 23.4%
      specificity. Reported indexes were within acceptable limits for screening tests.
      We suggest a sample increment and new testing with additional instruments.

PMID- 23882976
TI  - Cardiovascular adaptation and cardiac disease in the elite athlete.
AB  - Cardiovascular diseases are uncommon among trained athletes. Their occurrences
      mostly depend on the individual's age and fitness levels. Adequate understanding
      of the cardiovascular adaptations undergone by the competitive athletes' heart is
      of paramount importance in order to differentiate them from serious
      cardiovascular conditions. Diagnosing these abnormalities early may prevent rare
      but devastating potential complications associated with athletic activities and
      defines appropriate activity restrictions to minimize the risk of sudden cardiac
      death. This article will review concerns related to competitive athlete's
      cardiovascular adaptations and diseases, in light of specific recommendations
      presented in the 36th Bethesda Conference guidelines.

PMID- 23882977
TI  - Sudden cardiac death in the elite athlete.
AB  - Sudden cardiac death (SCD) is a long -recognized disease that occurs rarely in
      trained athletes. Most affected athletes have no symptoms before death. Many
      attempts have been made to detect those at risk for SCD before athletic
      participation. However, its overall clinical advantages remain questionable in
      medical literature. This article will review cardiogenic and non-cardiogenic
      causes of SCD as well as discuss how this entity affects those athletes older
      than 35 years.

PMID- 23882978
TI  - Persistent caruncular hyperemia revealing unsuspected orbital foreign body.
AB  - A peculiar case of a 13-years-old child with persistent caruncular hyperemia
      following trauma to the right eye with a tree branch which didn't improved after
      several days of oral and intravenous antibiotic therapy. Closer examination
      revealed organic foreign body that was not evident on initial evaluation,
      computerized tomography with and without contrast nor on magnetic resonance
      imaging. After removal of the organic foreign body symptoms resolved.

PMID- 23882979
TI  - Horner's syndrome: Herald of a ticking bomb.
AB  - Horner's syndrome is a clinical syndrome caused by damage to the cervical
      sympathetic ganglia. We discuss a case with classic signs of Horner's syndrome in
      an intravenous drug user with a right septic subclavian artery pseudoaneurysm.
      This case highlights that with the increasing intravenous drug use, this rare
      presentation of HS may become more common.

PMID- 23882980
TI  - Continuous spinal anesthesia for hip replacement in an elderly patient with an
      anterior mediastinal mass: a case report.
AB  - Incremental dosing of intrathecal local anesthetic for an indefinite duration
      performed during continuous spinal anesthesia (CSA) allows for better control of
      adverse effects caused by sympathetic nerve blockade. This case report describes
      a 91-year-old female with a left intertrochanteric fracture and a large thyroid
      mass causing contralateral anterior displacement of the trachea and the great
      vessels. We conducted a detailed investigation of the different techniques that
      can be used in such circumstances and the consequences each may have on a
      patient. We concluded that: better control of sympathetic nerve blockade and less
      adverse effects can be achieved with CSA, optimal management of thrombocytopenia
      should be done in a patient prior to regional anesthesia, and CSA is an
      anesthetic alternative to consider on elderly patients with an anterior
      mediastinal mass undergoing hip fracture surgery.

PMID- 23882981
TI  - Radiographical vignette: an apical lung density in an elderly man with
      hemoptysis.
AB  - An Aspergilloma is a "ball" of fungal mycelia composed of Aspergillus species
      developing in a pre-existing lung cavity. This uncommon entity may cause
      hemoptysis and may be a diagnostic challenge. We present imaging and review the
      literature of a recent case managed in our institution.

PMID- 23882982
TI  - [Coalitions in favor of patients].

PMID- 23882983
TI  - Neutropenia and thrombocytopenia in very low birth weight infants of women with
      preeclampsia.
AB  - OBJECTIVE: Determine the incidence of neutropenia and thrombocytopenia during the
      first week of life in very low birth weight (VLBW) infants born to mothers with
      preeclampsia. METHODS: Medical records of infants born to mothers with
      preeclampsia admitted to NICU from 2005-2007 were reviewed. RESULTS: A total of
      93 infants were included with a mean birth weight of 988 g and gestational age of
      29 weeks. Neutropenia was present in 49% of the infants and thrombocytopenia in
      56%. Infants with neutropenia had lower birth weights (p<0.01) and were born at
      lower gestational ages (p<0.01). Neutropenia was associated to a higher
      prevalence of positive blood cultures during the first week of life especially
      coagulase negative organisms. CONCLUSIONS: In this group of VLBW infants born to
      mothers with preeclampsia, neutropenia was common and it was associated to
      increase risk of bacterial infections during the first week of life.

PMID- 23882984
TI  - Differences in prevalence of inflammatory bowel disease in Puerto Rico between
      commercial and government-sponsored managed health care insured individuals.
AB  - BACKGROUND: Evaluation of ethnic and racial patterns of Inflammatory Bowel
      Disease (IBD) has demonstrated a higher incidence of IBD in Jews, and lower rates
      in blacks and Hispanics when compared to whites. There is limited data describing
      incidence and prevalence among Hispanics, the fastest growing minority in the
      United States. METHODS: To estimate the prevalence of IBD computerized records of
      all physicians billing and hospital discharges classified with ICD-9-CM IBD
      related codes were searched. Prevalence was estimated by age group, sex, and type
      of insurance (commercial versus government-sponsored managed care). RESULTS: Of
      1,248,993 insured individuals in 2005, 186 had a diagnosis of Crohn's disease and
      291 of ulcerative colitis. The estimated prevalence per 100,000 was 14.9 for
      Crohn's disease, 23.3 for ulcerative colitis, and 38.2 cases for IBD. The most
      significant difference was found when comparing insurance type, with a total IBD
      prevalence rate of 61.75 cases among commercial versus 14.36 cases among
      government-sponsored insured. CONCLUSIONS: The prevalence of IBD in this insured
      population in Puerto Rico places it among the highest described in a Hispanic
      population. Given the continued rise in prevalence of IBD and the limited studies
      describing the epidemiology of IBD in Hispanics, further studies which may
      provide important clues to the etiology of the disease as well as valuable
      information for appropriate health care planning are important.

PMID- 23882985
TI  - [Embolization of skull-base hypervascular tumors: description of a series of
      cases and proposal of a therapeutic algorithm].
AB  - Preoperative embolization allows reducing intraoperative blood loss caused by
      hypervascular intracranial tumors and its undesirable consequences. AIM: To
      describe the experience with preoperative endovascular embolization of
      hypervascular skull base tumors, and to develop a therapeutic algorithm.
      MATERIALS AND METHODS: A retrospective examination of preoperative neuroimaging
      and results of preoperative embolization was carried out. RESULTS: Fifteen cases
      were identified, with a median age of 36 years old, most of them harboring
      meningiomas, nasopharyngeal angiofibromas or paragangliomas. The external carotid
      artery was involved in 93% of cases and was the only afferent to 60%. In 27%,
      there were branches from the internal and external carotid arteries
      simultaneously. An extensive or complete occlusion grade was achieved in 95% of
      the branches of the external carotid artery. No branch of the internal carotid
      artery was treated, because poor contribution to tumor irrigation or was not
      possible to catheterize the pedicle. There were not recorded procedure-related
      complications. CONCLUSION: Based on the unification of the experiences described
      in this study and using data from published series, we present an algorithm for
      rational selection of skull base tumors that can benefit from preoperative
      embolization.

PMID- 23882986
TI  - [Exploration study of knowledge and attitudes related to prevention and
      transmission of dengue in Puerto Rico in 2012].
AB  - We got one of the most significant epidemics of the history of Dengue in Puerto
      Rico despite all major educational efforts made. The objective is to determine
      how much knowledge the people have about the prevention and transmission of
      Dengue virus. We administered a questionnaire of fifteen questions to 140 people
      of different communities at the metropolitan area as well as in the East area of
      Puerto Rico during the months of September to November of 2012. 88% were adults,
      100 were women and 40 men. The majority was from Caguas, Carolina, San Juan, and
      Bayamon. 60% were professionals. One hundred percent knew what Dengue is and 90%
      knows the mosquito. 77% of the participants know the actual epidemics, but the
      men got a 10% higher knowledge than women on the subject. Around 47% are not
      prepared to fight the Dengue virus, but they have great knowledge about the
      preventive measures and the clinical Management of Dengue Syndrome. 66% did not
      know that Puerto Rico has a Dengue Center from the CDC located at the Island.
      Only 17.5% of the participants knows that the Dengue Virus can be transmitted
      through transfusion of blood components. Our study met our objectives showing
      that we have good knowledge about Dengue, but there is poor knowledge about the
      transmission of Dengue Virus through transfusion of blood components. There is a
      big necessity to develop community strategies to eliminate this disease. We
      recommend repeating this study with more collaboration from other entities, more
      questions, and more participants.

PMID- 23882988
TI  - Cardiac amyloidosis secondary to multiple myeloma.
AB  - Amyloidosis is a multisystemic disease caused by extracellular deposition of
      pathologic beta fibrillar proteins in multiple organs. Deposited fibrils can be
      either innunoglobulin light chanis or amyloid-A protein. The incidence of
      anyloidosis derived from anyloid-A protein, usually associated to an underlying
      disease, has been dimisishing over the decades in the United States producing
      clinical evidence of cardiac involvement in less than 5% of all cases. The extent
      of cardiac involvement is the determining prognostic factor. Early diagnosis and
      therapy aimed at the underlying disease may halt progression of cardiac
      dysfuction and improve prognosis. We report a case of a 63-year-old man who was
      diagnosed with cardiac amyloidosis secondary to multiple myeloma.

PMID- 23882987
TI  - Cervical dysplasia and pre-term birth in San Juan city hospital: a cohort
      retrospective study.
AB  - Cervical dysplasia alters the release of cytokines and inflammatory mediators in
      pregnant woman with cervical dysplasia. This study evaluates a cohort of pregnant
      patients screened for cervical dysplasia to determine the relationship between
      cervical dysplasia and preterm labor (PTL). METHODS: Retrospective chart review
      of pregnant patients screened for cervical dysplasia at the San Juan City
      Hospital between October 2006 and December 2010. Patients with low or high-grade
      squamous intraepithelial lesions (LGSIL or HGSIL, respectively) were evaluated
      with colposcopy. Primary outcome was the event of PTL and the risk factor
      evaluated was presence of cervical dysplasia. RESULTS: A total of 2,059 patients
      were screened for cervical dysplasia and 59 were evaluated with colposcopy due to
      LGSIL or HGSIL. From those, 29% were negative for intraepithelial lesions and
      malignancy (NILM), 54% had cervical intraepithelial neoplasia (CIN)-1, 17% where
      diagnosed as CIN-2/3 where no invasive cervical cancer was identified. In the
      group of NILM, 24% had PTL compared to 18% in patients who screened negative on
      initial cytological evaluation. In cases where CIN-1 was confirmed by colposcopy
      28% had PTL compared with 40% in patients with CIN-2/3. Other risk factors
      associated with PTL were not significantly different among the groups.
      CONCLUSIONS: Cervical dysplasia in pregnancy may represent an increase risk for
      premature labor.

PMID- 23882989
TI  - Hypersensitive pneumonitis: a case report.
AB  - Hypersensitivity pneumonitis, also known as extrinsic allergic alveolitis,
      constitutes a spectrum of granulomatous, interstitial, bronchiolar, and alveolar
      filling lung diseases resulting from repeated inhalation and sensitization to a
      wide variety of organic aerosols and low-molecular-weight chemical antigens. We
      report a case of a 57 year-old-female with hypersensitive pneumonitis due to
      pigeon droppings. Early diagnosis during the acute phase of hypersensitive
      pneumonitis is important due to the irreversible damages caused by this chronic
      disease.

PMID- 23882990
TI  - The cardiology and endocrinology connection between amiodarone and
      thyrotoxicosis: case report and review of the literature.
AB  - Amiodarone is used in a large number of cardiac conditions. Amiodarone-induced
      thyroid dysfunction has been reported to affect up to 20% of users. Amiodarone
      can lead to both amiodarone-induced hypothyroidism (AIH) and less commonly
      amiodarone-induced thyrotoxicosis (AIT). There are two main forms of AIT. Type 1
      AIT, a form of io-dine-induced hyperthyroidism, and type 2, a drug-induced
      destructive thyroiditis. Type 1 AIT develops on individuals with underlying
      thyroid disease. Treatment of Type 1 AIT includes the use of antithyroid drugs
      and discontinuation of amiodarone. Type 2 AIT is commonly self-limiting in
      nature. In this article wedescribe a patient with Amiodarone-induced
      thyrotoxicosis discussing its clinical features and medical therapeutic approach.

PMID- 23882991
TI  - Solid pseudopapillary pancreatic tumor as a portal hypertension causal: the first
      reported case in Puerto Rico.
AB  - We describe the first reported case in Puerto Rico of Solid Pseudopapillary Tumor
      (SPT) of the pancreas causing portal hypertension. Clinical presentation and
      characteristic imaging findings are helpful to differentiate SPT from pancreatic
      carcinoma. Diagnosis can be confirmed by histopathological and
      immunohistochemical approach through biopsy. Timely surgical intervention can
      prevent portal hypertension as manifestation and be lifesaving in case of
      malignant degeneration, giving the patient an excellent prognosis after tumor
      surgical resection.

PMID- 23882992
TI  - Penetrating eye globe injury from trauma with a metallic nail: a case report.
AB  - We report a case of penetrating eye globe injury due to a metallic nail. This is
      the first case evaluated by our service that presented with an intact 2.5
      centimeter nail penetrating the right eye with a significant intraocular
      component that the patient did not remove. We describe the initial presentation
      and the multi-step surgery that this complicated injury required. The early
      postoperative visual acuity remained unchanged when compared to the presenting.
      In addition, the patient had no retinal pathology or optic nerve damage after the
      procedure.

PMID- 23882993
TI  - Ocular findings in patients with oculocutaneous albinism type ia with G47D
      tyrosinase gene mutation in Puerto Rico: a case report.
AB  - Previous studies have suggested that the G47D mutation leads patients to develop
      Oculocutaneous albinism (OCA) type IA. This mutation has been described in the
      Canary Islands. Historically, there has been a migration from the Canary Islands
      to some regions of Puerto Rico. OBJECTIVE: To report on the ocular findings of
      two Puerto Rican patients with OCA IA due to the G47D Tyrosinase gene mutation.
      PATIENT AND FINDINGS: Two unrelated patients with OCA underwent a comprehensive
      eye examination and were referred for genetic analysis. Patients had almost total
      iris transillumination, clear lenses, foveal hypoplasia with transparent maculae,
      and albinotic mid peripheries. Both patients had nystagmus, and only one patient
      had strabismus. CONCLUSIONS: Patients with the G47D muta- tion leading to OCA IA
      have poor visual acuities and poorly pigmented phenotypic ophthalmic findings.
      Further studies comparing ocular findings in patients th several mutations
      leading to OCA IA are warranted. To our knowledge this is the first report on
      ocular findings in Puerto Rican patients with OCA type IA with the rare G47D
      mutation.

PMID- 23882994
TI  - Mucormycosis of the vulva in an immunocompromised pediatric patient.
AB  - Primary cutaneous mucormycosis is very unusual and rarely reported in the
      literature. The diagnosis is difficult and may mimic several infectious and
      immunologic diseases. We report a case of vulvar mucormycosis in a pediatric
      patient with end stage renal disease. A female on her first decade of life
      presented with a small scar on the right labia majora that in matters of weeks
      progressed aggressively, ulcerated, extended to the contralateral labia and
      invaded the entir vulvar region. Subsequent surgical debridement was undertaken.
      Pathology revealed Mucor species with progressive tissue necrosis. The patient
      was successfully trea ed with systemic antifungal, wide debridement of the
      affected area, hyperbaric oxygen therapy and surgical reconstruction of the area

PMID- 23882995
TI  - Overview of thyroid physiology: an essential for understanding familial euthyroid
      multinodular goiter.
AB  - Nontoxic goiter is a diffuse or nodular enlargement of the thyroid gland that
      does not result from an inflammatory or neoplastic process and is not associated
      with abnormal thyroid function. Familial forms of goiter in areas not known to
      feature iodine deficiency are much less common. However, not all individuals in
      the same iodine deficiency region develop goiter and iodine supplementation does
      not prevent goiter development in all treated individuals. The etiology of
      euthyroid goiter is still incompletely understood. It is assumed that the
      development of goiter depends on various interactions between genetic and
      environmental factors. We present an overview on the thyroid physiology, which is
      important for a better understanding of Familial Euthyroid Multinodular Goiter.

PMID- 23882996
TI  - Foliar nickel application alleviates detrimental effects of glyphosate drift on
      yield and seed quality of wheat.
AB  - Glyphosate drift to nontarget crops causes growth aberrations and yield losses.
      This herbicide can also interact with divalent nutrients and form poorly soluble
      complexes. The possibility of using nickel (Ni), an essential divalent metal, for
      alleviating glyphosate drift damage to wheat was investigated in this study.
      Effects of Ni applications on various growth parameters, seed yield, and quality
      of durum wheat ( Triticum durum ) treated with sublethal glyphosate at different
      developmental stages were investigated in greenhouse experiments. Nickel
      concentrations of various plant parts and glyphosate-induced shikimate
      accumulation were measured. Foliar but not soil Ni applications significantly
      reduced glyphosate injuries including yield losses, stunting, and excessive
      tillering. Both shoot and grain Ni concentrations were enhanced by foliar Ni
      treatment. Seed germination and seedling vigor were impaired by glyphosate and
      improved by foliar Ni application to parental plants. Foliar Ni application
      appears to have a great potential to ameliorate glyphosate drift injury to wheat.

PMID- 23882997
TI  - FluoQ: a tool for rapid analysis of multiparameter fluorescence imaging data
      applied to oscillatory events.
AB  - The number of fluorescent sensors and their use in living cells has significantly
      increased in the past years. Yet, the analysis of data from single cells or cell
      populations usually remains a very time-consuming enterprise. Here, we introduce
      FluoQ, a new macro for the image analysis software ImageJ, which enables fast
      analysis of multiparameter time-lapse fluorescence microscopy data with minimal
      manual input. FluoQ provides statistical analysis of all measured parameters and
      delivers the results in multiple graphic and numeric displays. We demonstrate the
      power of FluoQ by applying the macro to data analysis in the development and
      optimization of novel FRET reporters for monitoring the performance of
      calcium/calmodulin-binding inositol trisphosphate kinases A and B (ITPKA and
      ITPKB) in HeLa cells. We find that conformational changes in the ITPKA-based
      sensor follow receptor-mediated calcium oscillations. This indicates that ITPKA
      contributes to the regulation of intracellular calcium transients by limiting
      inositol trisphosphate levels. 

PMID- 23882998
TI  - Large area IR microlens arrays of chalcogenide glass photoresists by grayscale
      maskless lithography.
AB  - The ability to use chalcogenide glass thin films as photoresists for one-step
      maskless grayscale lithographic patterning is demonstrated. It is shown that the
      chalcogenide photoresists can be used to fabricate grayscale patterns with smooth
      and continuous profiles such as arrays of cylindrical and spherical microlenses,
      which are useful as optical structures for IR applications. The etching and
      exposure parameters are optimized to obtain smooth reproducible lens arrays of
      150 MUm periodicity and up to ~170 nm height on large areas (~1 cm(2)). The
      roughness is found to increase as a function of the exposure dose and is
      attributed to the selective dissolution of the As-Se, As-As, and Se-Se bonds
      present in the nanodistributed phases and the presence of the oxide phase. Thus,
      a minimum exposure dose produces optimally patterned lens arrays. The focal
      length calculated for the smooth microlens array is ~9.3 mm, indicating the
      suitability of the lens arrays for focusing applications in the IR region. 

PMID- 23882999
TI  - Atomistic description of the folding of a dimeric protein.
AB  - Equilibrium molecular dynamics simulations are increasingly being used to
      describe the folding of individual proteins and protein domains at an atomic
      level of detail. Isolated protein domains, however, are rarely observed in vivo,
      where multidomain proteins and multimeric assemblies are far more common. It is
      clear that the folding of such proteins is often inextricably coupled with the
      process of dimerization; indeed, many protein monomers and protein domains are
      not stable in isolation, and fold to their native structures only when stabilized
      by interactions with other members of a protein complex. Here, we use equilibrium
      molecular dynamics simulations with an aggregate simulation length of 4 ms to
      elucidate key aspects of the folding mechanism, and of the associated free-energy
      surface, of the Top7-CFr dimer, a 114-amino-acid protein homodimer with a mixed
      alpha/beta structure. In these simulations, we observed a number of folding and
      unfolding events. Each folding event was characterized by the assembly of two
      unfolded Top7-CFr monomers to form a stable, folded dimer. We found that the
      isolated monomer is unstable but that, early in the folding pathway, nascent
      native structure is stabilized by contacts between the two monomer subunits.
      These contacts are in some cases native, as in an induced-folding model, and in
      other cases non-native, as in a fly-casting mechanism. Occasionally, folding by
      conformational selection, in which both subunits form independently before
      dimerization, was also observed. Folding then proceeds through the sequential
      addition of strands to the protein beta sheet. Although the long-time-scale
      relaxation of the folding process can be well described by a single exponential,
      these simulations reveal the presence of a number of kinetic traps, characterized
      by structures in which individual strands are added in an incorrect order. 

PMID- 23883000
TI  - Empirical study of correlated survival times for recurrent events with
      proportional hazards margins and the effect of correlation and censoring.
AB  - BACKGROUND: In longitudinal studies where subjects experience recurrent incidents
      over a period of time, such as respiratory infections, fever or diarrhea,
      statistical methods are required to take into account the within-subject
      correlation. METHODS: For repeated events data with censored failure, the
      independent increment (AG), marginal (WLW) and conditional (PWP) models are three
      multiple failure models that generalize Cox's proportional hazard model. In this
      paper, we revise the efficiency, accuracy and robustness of all three models
      under simulated scenarios with varying degrees of within-subject correlation,
      censoring levels, maximum number of possible recurrences and sample size. We also
      study the methods performance on a real dataset from a cohort study with
      bronchial obstruction. RESULTS: We find substantial differences between methods
      and there is not an optimal method. AG and PWP seem to be preferable to WLW for
      low correlation levels but the situation reverts for high correlations.
      CONCLUSIONS: All methods are stable in front of censoring, worsen with increasing
      recurrence levels and share a bias problem which, among other consequences, makes
      asymptotic normal confidence intervals not fully reliable, although they are well
      developed theoretically.

PMID- 23883002
TI  - Communication: quantum dynamics in classical spin baths.
AB  - A formalism for studying the dynamics of quantum systems embedded in classical
      spin baths is introduced. The theory is based on generalized antisymmetric
      brackets and predicts the presence of open-path off-diagonal geometric phases in
      the evolution of the density matrix. The weak coupling limit of the equation can
      be integrated by standard algorithms and provides a non-Markovian approach to the
      computer simulation of quantum systems in classical spin environments. It is
      expected that the theory and numerical schemes presented here have a wide
      applicability. 

PMID- 23883003
TI  - Communication: nonadiabatic ring-polymer molecular dynamics.
AB  - A new method based on an extension of ring-polymer molecular dynamics is proposed
      for the calculation of thermal correlation functions in electronically
      nonadiabatic systems. The ring-polymer dynamics are performed using a continuous
      variable representation of the electronic states within the mapping approach,
      such that the electronic and nuclear degrees of freedom are treated on an equal
      footing. Illustrative applications of the method show good agreement with exact
      quantum results for the dynamics over short to moderate times and reveal a
      systematic improvement over the classical implementation of the mapping approach
      (single-bead limit). Being based on trajectories, the method scales well with the
      number of degrees of freedom and will be applicable to simulate certain
      nonadiabatic processes in complex molecular systems. 

PMID- 23883004
TI  - A geometrical parametrization of C1'-C5' RNA ribose chemical shifts calculated by
      density functional theory.
AB  - It has been recently shown that NMR chemical shifts can be used to determine the
      structures of proteins. In order to begin to extend this type of approach to
      nucleic acids, we present an equation that relates the structural parameters and
      the (13)C chemical shifts of the ribose group. The parameters in the equation
      were determined by maximizing the agreement between the DFT-derived chemical
      shifts and those predicted through the equation for a database of ribose
      structures. Our results indicate that this type of approach represents a
      promising way of establishing quantitative and computationally efficient
      analytical relationships between chemical shifts and structural parameters in
      nucleic acids. 

PMID- 23883005
TI  - Reduced explicitly correlated Hartree-Fock approach within the nuclear-electronic
      orbital framework: theoretical formulation.
AB  - The nuclear-electronic orbital (NEO) method treats electrons and select nuclei
      quantum mechanically on the same level to extend beyond the Born-Oppenheimer
      approximation. Electron-nucleus dynamical correlation has been found to be highly
      significant due to the attractive Coulomb interaction. The explicitly correlated
      Hartree-Fock (NEO-XCHF) approach includes explicit electron-nucleus correlation
      with Gaussian-type geminal functions during the variational optimization of the
      nuclear-electronic wavefunction. Although accurate for small model systems, the
      NEO-XCHF method is computationally impractical for larger chemical systems. In
      this paper, we develop the reduced explicitly correlated Hartree-Fock approach,
      denoted NEO-RXCHF, where only select electronic orbitals are explicitly
      correlated to the nuclear orbitals. By explicitly correlating only the relevant
      electronic orbitals to the nuclear orbitals, the NEO-RXCHF approach avoids
      problems that can arise when all electronic orbitals are explicitly correlated to
      the nuclear orbitals in the same manner. We examine three different NEO-RXCHF
      methods that differ in the treatment of the exchange between the geminal-coupled
      electronic orbitals and the other electronic orbitals: NEO-RXCHF-fe is fully
      antisymmetric with respect to exchange of all electronic coordinates and includes
      all electronic exchange terms; NEO-RXCHF-ne neglects the exchange between the
      geminal-coupled electronic orbitals and the other electronic orbitals; and NEO
      RXCHF-ae includes approximate exchange terms between the geminal-coupled
      electronic orbitals and the other electronic orbitals. The latter two NEO-RXCHF
      methods offer substantial computational savings over the NEO-XCHF approach. The
      NEO-RXCHF approach is applicable to a wide range of chemical systems that exhibit
      non-Born-Oppenheimer effects between electrons and nuclei, as well as positron
      containing molecular systems. 

PMID- 23883001
TI  - Heterogeneous susceptibility of circulating SIV isolate capsids to HIV
      interacting factors.
AB  - BACKGROUND: Many species of non-human primates in Africa are naturally infected
      by simian immunodeficiency viruses (SIV) and humans stand at the forefront of
      exposure to these viruses in Sub-Saharan Africa. Cross-species transmission and
      adaptation of SIV to humans have given rise to human immunodeficiency viruses
      (HIV-1 and HIV-2) on twelve accountable, independent occasions. However, the
      determinants contributing to a simian-to-human lasting transmission are not fully
      understood. Following entry, viral cores are released into the cytoplasm and
      become the principal target of host cellular factors. Here, we evaluated cellular
      factors likely to be involved in potential new SIV cross-species transmissions.
      We investigated the interactions of capsids from naturally circulating SIV
      isolates with both HIV-1 restricting (i.e. TRIM5 proteins) and facilitating (i.e.
      cyclophilin A and nucleopore-associated Nup358/RanBP2 and Nup153) factors in
      single-round infectivity assays that reproduce early stages of the viral life
      cycle. RESULTS: We show that human TRIM5alpha is unlikely to prevent cross
      species transmission of any SIV we tested and observed that the SIV CA-CypA
      interaction is a widespread but not a universal feature. Moreover, entry in the
      nucleus of different SIV appeared to follow pathways that do not necessarily
      recruit Nup358/RanBP2 or Nup153, and this regardless of their interaction with
      CypA. Nevertheless, we found that, like HIV-1, human-adapted HIV-2 infection was
      dependent on Nup358/RanBP2 and Nup153 interactions for optimal infection.
      Furthermore, we found that, unlike HIV CA, SIV CA did not require a direct
      interaction with the Cyp-like domain of Nup358/RanBP2 to carry out successful
      infection. CONCLUSIONS: Circulating SIV present a variety of phenotypes with
      regard to CA-interacting restricting or facilitating factors. Altogether, we
      unveiled unidentified pathways for SIV CA, which could also be exploited by HIV
      in different cellular contexts, to drive entry into the nucleus. Our findings
      warrant a closer evaluation of other potential defenses against circulating SIV.

PMID- 23883006
TI  - Reduced explicitly correlated Hartree-Fock approach within the nuclear-electronic
      orbital framework: applications to positronic molecular systems.
AB  - In the application of the nuclear-electronic orbital (NEO) method to positronic
      systems, all electrons and the positron are treated quantum mechanically on the
      same level. Explicit electron-positron correlation can be included using Gaussian
      type geminal functions within the variational self-consistent-field procedure. In
      this paper, we apply the recently developed reduced explicitly correlated Hartree
      Fock (RXCHF) approach to positronic molecular systems. In the application of
      RXCHF to positronic systems, only a single electronic orbital is explicitly
      correlated to the positronic orbital. We apply NEO-RXCHF to three systems:
      positron-lithium, lithium positride, and positron-lithium hydride. For all three
      of these systems, the RXCHF approach provides accurate two-photon annihilation
      rates, average contact densities, electronic and positronic single-particle
      densities, and electron-positron contact densities. Moreover, the RXCHF approach
      is significantly more accurate than the original XCHF approach, in which all
      electronic orbitals are explicitly correlated to the positronic orbital in the
      same manner, because the RXCHF wavefunction is optimized to produce a highly
      accurate description of the short-ranged electron-positron interaction that
      dictates the annihilation rates and other local properties. Furthermore, RXCHF
      methods that neglect or approximate the electronic exchange interactions between
      the geminal-coupled electronic orbital and the regular electronic orbitals lead
      to virtually identical annihilation rates and densities as the fully
      antisymmetric RXCHF method but offer substantial advantages in computational
      tractability. Thus, NEO-RXCHF is a promising, computationally practical approach
      for studying larger positron-containing systems. 

PMID- 23883007
TI  - Free energy calculations for molecular solids using GROMACS.
AB  - In this work, we describe a procedure to evaluate the free energy of molecular
      solids with the GROMACS molecular dynamics package. The free energy is calculated
      using the Einstein molecule method that can be regarded as a small modification
      of the Einstein crystal method. Here, the position and orientation of the
      molecules is fixed by using an Einstein field that binds with harmonic springs at
      least three non-collinear atoms (or points of the molecule) to their reference
      positions. The validity of the Einstein field is tested by performing free-energy
      calculations of methanol, water (ice), and patchy colloids molecular solids. The
      free energies calculated with GROMACS show a very good agreement with those
      obtained using Monte Carlo and with previously published results. 

PMID- 23883008
TI  - Comparison of low-rank tensor expansions for the acceleration of quantum
      chemistry computations.
AB  - Low-rank spectral expansion and tensor hypercontraction are two promising
      techniques for reducing the size of the two-electron excitation tensor by
      factorizing it into products of smaller tensors. Both methods can potentially
      realize an O(r(4)) quantum chemistry method where r is the number of one-electron
      orbitals. We compare the two factorizations in this paper by applying them to the
      parametric 2-electron reduced density matrix method with the M functional [D. A.
      Mazziotti, Phys. Rev. Lett. 101, 253002 (2008)]. We study several inorganic
      molecules, alkane chains, and potential curves as well as reaction and
      dissociation energies. The low-rank spectral expansion, we find, is typically
      more efficient than tensor hypercontraction due to a faster convergence of the
      energy and a smaller constant prefactor in the energy optimization. Both
      factorizations are applicable to the acceleration of a wide range of wavefunction
      and reduced-density-matrix methods. 

PMID- 23883009
TI  - Functional thermo-dynamics: a generalization of dynamic density functional theory
      to non-isothermal situations.
AB  - We present a generalization of Density Functional Theory (DFT) to non-equilibrium
      non-isothermal situations. By using the original approach set forth by Gibbs in
      his consideration of Macroscopic Thermodynamics (MT), we consider a Functional
      Thermo-Dynamics (FTD) description based on the density field and the energy
      density field. A crucial ingredient of the theory is an entropy functional, which
      is a concave functional. Therefore, there is a one to one connection between the
      density and energy fields with the conjugate thermodynamic fields. The connection
      between the three levels of description (MT, DFT, FTD) is clarified through a
      bridge theorem that relates the entropy of different levels of description and
      that constitutes a generalization of Mermin's theorem to arbitrary levels of
      description whose relevant variables are connected linearly. Although the FTD
      level of description does not provide any new information about averages and
      correlations at equilibrium, it is a crucial ingredient for the dynamics in non
      equilibrium states. We obtain with the technique of projection operators the set
      of dynamic equations that describe the evolution of the density and energy
      density fields from an initial non-equilibrium state towards equilibrium. These
      equations generalize time dependent density functional theory to non-isothermal
      situations. We also present an explicit model for the entropy functional for hard
      spheres. 

PMID- 23883010
TI  - An improved treatment of empirical dispersion and a many-body energy
      decomposition scheme for the explicit polarization plus symmetry-adapted
      perturbation theory (XSAPT) method.
AB  - We recently introduced a low-cost quantum chemistry method for computing
      intermolecular interactions, combining a monomer-based self-consistent field
      calculation (the "explicit polarization" method, XPol) with pairwise-additive
      symmetry adapted perturbation theory (SAPT). The method uses Kohn-Sham (KS)
      orbitals in the SAPT formalism but replaces the SAPT dispersion and exchange
      dispersion terms with empirical potentials ("+D"), and we called this method
      XPol+SAPT(KS)+D. Here, we report a second-generation version of this approach,
      XPol+SAPT(KS)+D2 or XSAPT(KS)+D2 for short, in which we have modified the form of
      the empirical atom-atom dispersion potentials. Accurate binding energies are
      obtained for benchmark databases of dimer binding energies, and potential energy
      curves are captured accurately for a variety of challenging systems. We suggest
      that using different asymptotic corrections for different monomers is necessary
      to get good binding energies in general, especially for hydrogen-bonded
      complexes. As compared to our original "+D" formulation, the second-generation
      "+D2" method accurately reproduces not only total binding energies but also the
      various components of the interaction energy, and on this basis we introduce an
      energy decomposition scheme that extends traditional SAPT energy decomposition to
      systems containing more than two monomers. For (H2O)6, the many-body contribution
      to the interaction energy agrees well with that obtained from traditional Kitaura
      Morokuma energy decomposition analysis in a large basis set. 

PMID- 23883011
TI  - A guiding potential method for evaluating the bending rigidity of tensionless
      lipid membranes from molecular simulation.
AB  - A new method is proposed to estimate the bending rigidity of lipid membranes from
      molecular dynamics simulations. An external cylindrical guiding potential is used
      to impose a sinusoidal deformation to a planar membrane. The bending rigidity is
      obtained from the mean force acting on the cylinder by calibrating against a
      discretized Helfrich model that accounts for thermal fluctuations of the membrane
      surface. The method has been successfully applied to a dimyristoyl
      phosphatidylcholine bilayer simulated with a coarse-grained model. A well
      converged bending rigidity was obtained for the tension-free membrane and showed
      reasonable agreement with that obtained from the height fluctuation spectrum. 

PMID- 23883012
TI  - Local unitary transformation method toward practical electron correlation
      calculations with scalar relativistic effect in large-scale molecules.
AB  - In order to perform practical electron correlation calculations, the local
      unitary transformation (LUT) scheme at the spin-free infinite-order Douglas-Kroll
      Hess (IODKH) level [J. Seino and H. Nakai, J. Chem. Phys. 136, 244102 (2012); and
      ibid. 137, 144101 (2012)], which is based on the locality of relativistic
      effects, has been combined with the linear-scaling divide-and-conquer (DC)-based
      Hartree-Fock (HF) and electron correlation methods, such as the second-order
      Moller-Plesset (MP2) and the coupled cluster theories with single and double
      excitations (CCSD). Numerical applications in hydrogen halide molecules, (HX)n (X
      = F, Cl, Br, and I), coinage metal chain systems, Mn (M = Cu and Ag), and
      platinum-terminated polyynediyl chain, trans,trans-{(p
      CH3C6H4)3P}2(C6H5)Pt(C=C)4Pt(C6H5){(p-CH3C6H4)3P}2, clarified that the present
      methods, namely DC-HF, MP2, and CCSD with the LUT-IODKH Hamiltonian, reproduce
      the results obtained using conventional methods with small computational costs.
      The combination of both LUT and DC techniques could be the first approach that
      achieves overall quasi-linear-scaling with a small prefactor for relativistic
      electron correlation calculations. 

PMID- 23883013
TI  - Grand-canonical quantized liquid density-functional theory in a Car-Parrinello
      implementation.
AB  - Quantized Liquid Density-Functional Theory (QLDFT) [S. Patchkovskii and T. Heine,
      Phys. Rev. E 80, 031603 (2009)], a method developed to assess the adsorption of
      gas molecules in porous nanomaterials, is reformulated within the grand canonical
      ensemble. With the grand potential it is possible to compare directly external
      and internal thermodynamic quantities. In our new implementation, the grand
      potential is minimized utilizing the Car-Parrinello approach and gives, in
      particular for low temperature simulations, a significant computational advantage
      over the original canonical approaches. The method is validated against original
      QLDFT, and applied to model potentials and graphite slit pores. 

PMID- 23883014
TI  - Second-order many-body perturbation expansions of vibrational Dyson self
      energies.
AB  - Second-order many-body perturbation theories for anharmonic vibrational
      frequencies and zero-point energies of molecules are formulated, implemented, and
      tested. They solve the vibrational Dyson equation self-consistently by taking
      into account the frequency dependence of the Dyson self-energy in the diagonal
      approximation, which is expanded in a diagrammatic perturbation series up to
      second order. Three reference wave functions, all of which are diagrammatically
      size consistent, are considered: the harmonic approximation and diagrammatic
      vibrational self-consistent field (XVSCF) methods with and without the first
      order Dyson geometry correction, i.e., XVSCF[n] and XVSCF(n), where n refers to
      the truncation rank of the Taylor-series potential energy surface. The
      corresponding second-order perturbation theories, XVH2(n), XVMP2[n], and
      XVMP2(n), are shown to be rigorously diagrammatically size consistent for both
      total energies and transition frequencies, yield accurate results (typically
      within a few cm(-1) at n = 4 for water and formaldehyde) for both quantities even
      in the presence of Fermi resonance, and have access to fundamentals, overtones,
      and combinations as well as their relative intensities as residues of the
      vibrational Green's functions. They are implemented into simple algorithms that
      require only force constants and frequencies of the reference methods (with no
      basis sets, quadrature, or matrix diagonalization at any stage of the
      calculation). The rules for enumerating and algebraically interpreting energy and
      self-energy diagrams are elucidated in detail. 

PMID- 23883015
TI  - Relation of exact Gaussian basis methods to the dephasing representation: theory
      and application to time-resolved electronic spectra.
AB  - We recently showed that the dephasing representation (DR) provides an efficient
      tool for computing ultrafast electronic spectra and that further acceleration is
      possible with cellularization [M. Sulc and J. Vanicek, Mol. Phys. 110, 945
      (2012)]. Here, we focus on increasing the accuracy of this approximation by first
      implementing an exact Gaussian basis method, which benefits from the accuracy of
      quantum dynamics and efficiency of classical dynamics. Starting from this exact
      method, the DR is derived together with ten other methods for computing time
      resolved spectra with intermediate accuracy and efficiency. These methods include
      the Gaussian DR, an exact generalization of the DR, in which trajectories are
      replaced by communicating frozen Gaussian basis functions evolving classically
      with an average Hamiltonian. The newly obtained methods are tested numerically on
      time correlation functions and time-resolved stimulated emission spectra in the
      harmonic potential, pyrazine S0/S1 model, and quartic oscillator. Numerical
      results confirm that both the Gaussian basis method and the Gaussian DR increase
      the accuracy of the DR. Surprisingly, in chaotic systems the Gaussian DR can
      outperform the presumably more accurate Gaussian basis method, in which the two
      bases are evolved separately. 

PMID- 23883016
TI  - Body-fixed relativistic molecular Hamiltonian and its application to nuclear spin
      rotation tensor: linear molecules.
AB  - The relativistic molecular Hamiltonian written in the body-fixed frame of
      reference is the basis for high-precision calculations of spectroscopic
      parameters involving nuclear vibrations and/or rotations. Such a Hamiltonian that
      describes electrons fully relativistically and nuclei quasi-relativistically is
      just developed for semi-rigid nonlinear molecules [Y. Xiao and W. Liu, J. Chem.
      Phys. 138, 134104 (2013)]. Yet, the formulation should somewhat be revised for
      linear molecules thanks to some unusual features arising from the redundancy of
      the rotation around the molecular axis. Nonetheless, the resulting isomorphic
      Hamiltonian is rather similar to that for nonlinear molecules. Consequently, the
      relativistic formulation of nuclear spin-rotation (NSR) tensor for linear
      molecules is very much the same as that for nonlinear molecules. So is the
      relativistic mapping between experimental NSR and NMR. 

PMID- 23883017
TI  - Transport of finite size particles in confined narrow channels: diffusion,
      coherence, and particle separation.
AB  - Transport of the finite size spherical Brownian particles is investigated in
      confined narrow channels with varying cross-section width. Applying the Fick
      Jacobs approximation, we obtain the expressions of the particle current, the
      effective diffusion coefficient, and the coherence level of Brownian transport
      (the Peclet number). For the case of the biased constant force, the dependencies
      of the nonlinear mobility, the effective diffusion coefficient, and the Peclet
      number on the particle size exhibit striking behaviors. The Peclet number
      decreases with increasing the radius of the particle which shows that the big
      sizes of the particles reduce the coherence level of Brownian transport. There
      exists an optimized value of the radius at which the effective diffusion
      coefficient is maximal. For the case of the asymmetric unbiased force, due to the
      competition between the spatial asymmetry and the temporal asymmetry, the
      transport directions of the particles depend very sensitively on the size of the
      particle. Particles larger than a given threshold radius move to the left,
      whereas particles smaller than that move to the right. Therefore, one can
      separate particles of different radii and make them move towards opposite
      directions. 

PMID- 23883018
TI  - A novel correction scheme for DFT: a combined vdW-DF/CCSD(T) approach.
AB  - A system-specific but very accurate density functional theory (DFT) correction
      scheme is proposed for precise calculations of adsorbent-adsorbate interactions
      by combining the non-empirical van der Waals density functional (vdW-DF) method
      and the empirical DFT/CC correction scheme to reach accuracy of the coupled
      clusters method with single, double and perturbative triple excitations
      (CCSD(T)). The new approach is applied to small molecules (CH4, CO2, H2, H2O, N2)
      interacting with silica surfaces and purely siliceous microporous solids. The vdW
      DF/CC results for a perfectly reconstructed alpha-quartz surface are consistent
      with other dispersion-corrected DFT methods. Corrected for ZPVE, the vdW-DF/CC
      enthalpies of adsorption in pure-silica zeolite LTA (DeltaHads(0 K)) of 3.6 and
      5.2 kcal/mol for methane and carbon dioxide, respectively, are in excellent
      agreement with experimental values of 3.6 and 5.0 kcal/mol. The very high
      accuracy of the new scheme and its relatively easy use and numerical stability as
      compared to the earlier DFT/CC scheme offer a straightforward solution for
      obtaining reliable predictions of adsorption energies.

PMID- 23883019
TI  - Quantum tomography of a molecular bond in ice.
AB  - We present the moving picture of a molecular bond, in phase-space, in real-time,
      at resolution limited by quantum uncertainty. The images are tomographically
      reconstructed Wigner distribution functions (WDF) obtained from four-wave mixing
      measurements on Br2-doped ice. The WDF completely characterizes the dissipative
      quantum evolution of the system, which despite coupling to the environment
      retains quantum coherence, as evidenced by its persistent negative Wigner hole.
      The spectral decomposition of the WDF allows a direct visualization of
      wavefunctions and spatiotemporal coherences of the system and the system-bath
      interaction. The measurements vividly illustrate nonclassical wave mechanics in a
      many-body system, in ordinary condensed matter. 

PMID- 23883020
TI  - Investigation of the spin-lattice relaxation of 13CO and 13CO2 adsorbed in the
      metal-organic frameworks Cu3(btc)2 and Cu(3-x)Zn(x)(btc)2.
AB  - The (13)C nuclear spin-lattice relaxation time of (13)CO and (13)CO2 molecules
      adsorbed in the metal-organic frameworks (MOFs) Cu2.97Zn0.03(btc)2 and Cu3(btc)2
      is investigated over a wide range of temperatures at resonance frequencies of
      75.468 and 188.62 MHz. In all cases a mono-exponential relaxation is observed,
      and the (13)C spin-lattice relaxation times (T1) reveal minima within the
      temperature range of the measurements and both frequencies. This allows us to
      carry out a more detailed analysis of the (13)C spin relaxation data and to
      consider the influence due to the spectral functions of the thermal motion. In a
      model-free discussion of the temperature dependence of the ratios T1 (T)/T1,min
      we observe a motional mechanism that can be described by a single correlation
      time. In relation to the discussion of the relaxation mechanisms this can be
      understood in terms of dominating translational motion with mean jump distance
      being larger than the minimum distances between neighboring adsorption sites in
      the MOFs. A more detailed discussion of the jump-like motion observed here might
      be carried out on the basis of self-diffusion coefficients. From the present spin
      relaxation measurements activation energies for the local motion of the adsorbed
      molecules in the MOFs can be estimated to be 3.3 kJ/mol and 2.2 kJ/mol, for CO
      and CO2 molecules, respectively. Finally, our findings are compared with our
      recent results derived from the (13)C line shape analysis. 

PMID- 23883021
TI  - Reliable modeling of the electronic spectra of realistic uranium complexes.
AB  - We present an EOMCCSD (equation of motion coupled cluster with singles and
      doubles) study of excited states of the small [UO2](2+) and [UO2](+) model
      systems as well as the larger U(VI)O2(saldien) complex. In addition, the triples
      contribution within the EOMCCSDT and CR-EOMCCSD(T) (completely renormalized
      EOMCCSD with non-iterative triples) approaches for the [UO2](2+) and [UO2](+)
      systems as well as the active-space variant of the CR-EOMCCSD(T) method-CR
      EOMCCSd(t)-for the U(VI)O2(saldien) molecule are investigated. The coupled
      cluster data were employed as benchmark to choose the "best" appropriate exchange
      correlation functional for subsequent time-dependent density functional (TD-DFT)
      studies on the transition energies for closed-shell species. Furthermore, the
      influence of the saldien ligands on the electronic structure and excitation
      energies of the [UO2](+) molecule is discussed. The electronic excitations as
      well as their oscillator dipole strengths modeled with TD-DFT approach using the
      CAM-B3LYP exchange-correlation functional for the [U(V)O2(saldien)](-) with
      explicit inclusion of two dimethyl sulfoxide molecules are in good agreement with
      the experimental data of Takao et al. [Inorg. Chem. 49, 2349 (2010)]. 

PMID- 23883022
TI  - The X+ 2Pig, A+ 2Piu, B+ 2Deltau, and a+ 4Sigmau(-) electronic states of Cl2(+)
      studied by high-resolution photoelectron spectroscopy.
AB  - Partially rotationally resolved pulsed-field-ionization zero-kinetic-energy
      photoelectron spectra of the three isotopomers ((35)Cl2, (35)Cl(37)Cl, and
      (37)Cl2) of Cl2 have been recorded in the wavenumber ranges 92,500-96,500 cm(-1),
      corresponding to transitions to the low vibrational levels of the X(+) (2)Pig
      (Omega = 3/2, 1/2) ground state of Cl2 (+), and 106,750-115,500 cm(-1), where the
      a(+) (4)Sigmau (-)<-X(1)Sigmag (+), A(+) (2)Piu<-X(1)Sigmag (+), and B(+)
      (2)Deltau<-X(1)Sigmag (+) band systems overlap with transitions to high
      vibrational levels (v(+) > 25) of the X(+) state. The observation of Franck
      Condon-forbidden transitions to vibrational levels of the X(+) state of the
      cation with v(+) >= 25 is rationalized by a mechanism involving vertical
      excitation of predissociative Rydberg states of mixed singlet-triplet character
      with an A(+) ion core which are coupled to Rydberg states converging to high-v(+)
      levels of the X(+) state. The same mechanism is proposed to also be responsible
      for the observation of Cl(+) - Cl(-) ion pairs and quartet states in the
      photoionization of Cl2. The potential energy function of the X(+) state of Cl2
      (+) was determined in a direct fit to the experimental data. Transitions to
      vibrational levels of the A(+) (2)Piu, 3/2 and B(+) (2)Deltau, 3/2 states of Cl2
      (+) could be identified using the results of a recent analysis of the strong
      perturbation between the A(+) (2)Piu, 3/2 and B(+) (2)Deltau, 3/2 states of Cl2
      (+) observed in the A(+) - X(+) band system [Gharaibeh et al., J. Chem. Phys.
      137, 194317 (2012)], and transitions to several vibrational levels of the upper
      spin-orbit component ((2)Piu, 1/2) of the A(+) state were detected in the
      photoelectron spectrum of Cl2 (+). The a(+) (4)Sigmau (-)<-X(1)Sigmag (+)
      photoelectron band system, which is nominally forbidden by single-photon
      ionization from the ground state was also observed for the first time and its
      vibrational and spin-orbit structures were analyzed. The (4)Sigmau (-) state is
      split into two spin-orbit components with Omega = 1/2 and Omega = 3/2, separated
      by 37.5 cm(-1). The vibrational energy level structure of both components is
      regular, which indicates that the splitting results from the interaction with one
      or more distant ungerade Omega = 1/2 or Omega = 3/2 electronic states.

PMID- 23883023
TI  - X-ray absorption fine structure study of multinuclear copper(I) thiourea mixed
      ligand complexes.
AB  - X-ray absorption fine structure spectra of five copper(I) thiourea complexes
      [Cu4(thu)6 (NO3)4 (H2O)4] (1), [Cu4(thu)9 (NO3)4 (H2O)4] (2), [Cu2(thu)6 (SO4)
      H2O] (3), [Cu2(thu)5 (SO4) (H2O)3] (4), and [Cu(thu)Cl 0.5H2O] (5) have been
      investigated. Complexes 1 and 3 are supposed to have one type of copper centers
      in trigonal planar and tetrahedral environment, respectively. Complexes 2 and 4
      are supposed to have two types of copper centers, one center having trigonal
      planar geometry and another center having tetrahedral geometry. The aim of the
      present work is to show how extended X-ray absorption fine structure (EXAFS)
      spectra of these complexes, having different types of coordination environment,
      can be analyzed to yield the coordination geometry around one type of copper
      centers present in complexes 1 and 3, and two types of copper centers present in
      complexes 2 and 4. The crystal structure of complex 5 is unavailable due to
      inability of growing its single crystals, and hence the coordination geometry of
      this complex has been determined from EXAFS. The structural parameters determined
      from the EXAFS spectra have been reported and the coordination geometry has been
      depicted for the metal centers present in all the five complexes. Also, the
      chemical shifts have been used to determine the oxidation state of copper in
      these complexes. The X-ray absorption near edge spectra features have also been
      correlated with the coordination geometry. Also, the presence of both three and
      four coordinated Cu(I) centers in complexes 2 and 4 has been suggested from a
      comparison of the intensity of the feature at 8984 eV with those of 1 and 3.
      Further, in case of complex 5, the high intensity of peak A at 8986.5 eV is found
      to correspond to the presence of Cl coordinated to the copper center. 

PMID- 23883024
TI  - The interaction of He with vibrating HCN: potential energy surface, bound states,
      and rotationally inelastic cross sections.
AB  - A four-dimensional potential energy surface representing the interaction between
      He and hydrogen cyanide (HCN) subjected to bending vibrational motion is
      presented. Ab initio calculations were carried out at the coupled-cluster level
      with single and double excitations and a perturbative treatment of triple
      excitations, using a quadruple-zeta basis set and mid-bond functions. The global
      minimum is found in the linear He-HCN configuration with the H atom pointing
      towards helium at the intermolecular separation of 7.94 a0. The corresponding
      well depth is 30.35 cm(-1). First, the quality of the new potential has been
      tested by performing two comparisons with previous theoretical and experimental
      works. (i) The rovibrational energy levels of the He-HCN complex for a rigid
      linear configuration of the HCN molecule have been calculated. The dissociation
      energy is 8.99 cm(-1), which is slightly smaller than the semi-empirical value of
      9.42 cm(-1). The transitions frequencies are found to be in good agreement with
      the experimental data. (ii) We performed close coupling calculations of the
      rotational de-excitation of rigid linear HCN in collision with He and observed a
      close similarity with the theoretical data published in a recent study. Second,
      the effects of the vibrational bending of HCN have been investigated, both for
      the bound levels of the He-HCN system and for the rotationally inelastic cross
      sections. This was performed with an approximate method using the average of the
      interaction potential over the vibrational bending wavefunction. While this
      improves slightly the comparison of calculated transitions frequencies with
      experiment, the cross sections remain very close to those obtained with rigid
      linear HCN. 

PMID- 23883025
TI  - Refinement of the Robert-Bonamy formalism: considering effects from the line
      coupling.
AB  - Since it was developed in 1979, the Robert-Bonamy (RB) formalism has been widely
      used in calculating pressure broadened half-widths and induced shifts for many
      molecular systems. However, this formalism contains several approximations whose
      applicability has not been thoroughly justified. One of them is that lines of
      interest are well isolated. When these authors developed the formalism, they have
      relied on this assumption twice. First, in calculating the spectral density
      F(omega), they have only considered the diagonal matrix elements of the
      relaxation operator. Due to this simplification, effects from the line mixing are
      ignored. Second, when they applied the linked cluster theorem to remove the
      cutoff, they have assumed the matrix elements of the operator exp(-iS1 - S2) can
      be replaced by the exponential of the matrix elements of -iS1 - S2. With this
      replacement, effects from the line coupling are also ignored. Although both these
      two simplifications relied on the same approximation, their validity criteria are
      completely different and the latter is more stringent than the former. As a
      result, in many cases where the line mixing becomes negligible, significant
      effects from the line coupling have been completely missed. In the present study,
      we have developed a new method to evaluate the matrix elements of exp(-iS1 - S2)
      and have refined the RB formalism such that line coupling can be taken into
      account. Our numerical calculations of the half-widths for Raman Q lines of the
      N2-N2 pair have demonstrated that effects from the line coupling are important.
      In comparison with values derived from the RB formalism, new calculated values
      for these lines are significantly reduced. A recent study has shown that in
      comparison with the measurements and the most accurate close coupling
      calculations, the RB formalism overestimates the half-widths by a large amount.
      As a result, the refinement of the RB formalism goes in the right direction and
      these new calculated half-widths become closer to the "true" values. 

PMID- 23883026
TI  - A dynamical (e,2e) investigation of the structurally related cyclic ethers
      tetrahydrofuran, tetrahydropyran, and 1,4-dioxane.
AB  - Triple differential cross section measurements for the electron-impact ionization
      of the highest occupied molecular orbitals of tetrahydropyran and 1,4-dioxane are
      presented. For each molecule, experimental measurements were performed using the
      (e,2e) technique in asymmetric coplanar kinematics with an incident electron
      energy of 250 eV and an ejected electron energy of 20 eV. With the scattered
      electrons being detected at -5 degrees , the angular distributions of the ejected
      electrons in the binary and recoil regions were observed. These measurements are
      compared with calculations performed within the molecular 3-body distorted wave
      model. Here, reasonable agreement was observed between the theoretical model and
      the experimental measurements. These measurements are compared with results from
      a recent study on tetrahydrofuran [D. B. Jones, J. D. Builth-Williams, S. M.
      Bellm, L. Chiari, C. G. Ning, H. Chaluvadi, B. Lohmann, O. Ingolfsson, D.
      Madison, and M. J. Brunger, Chem. Phys. Lett. 572, 32 (2013)] in order to
      evaluate the influence of structure on the dynamics of the ionization process
      across this series of cyclic ethers. 

PMID- 23883027
TI  - Relativistic density functional theory modeling of plutonium and americium higher
      oxide molecules.
AB  - The results of electronic structure modeling of plutonium and americium higher
      oxide molecules (actinide oxidation states VI through VIII) by two-component
      relativistic density functional theory are presented. Ground-state equilibrium
      molecular structures, main features of charge distributions, and energetics of
      AnO3, AnO4, An2On (An=Pu, Am), and PuAmOn, n = 6-8, are determined. In all cases,
      molecular geometries of americium and mixed plutonium-americium oxides are
      similar to those of the corresponding plutonium compounds, though chemical
      bonding in americium oxides is markedly weaker. Relatively high stability of the
      mixed heptoxide PuAmO7 is noticed; the Pu(VIII) and especially Am(VIII) oxides
      are expected to be unstable. 

PMID- 23883028
TI  - Solvation dynamics of tryptophan in water-dimethyl sulfoxide binary mixture: in
      search of molecular origin of composition dependent multiple anomalies.
AB  - Experimental and simulation studies have uncovered at least two anomalous
      concentration regimes in water-dimethyl sulfoxide (DMSO) binary mixture whose
      precise origin has remained a subject of debate. In order to facilitate time
      domain experimental investigation of the dynamics of such binary mixtures, we
      explore strength or extent of influence of these anomalies in dipolar solvation
      dynamics by carrying out long molecular dynamics simulations over a wide range of
      DMSO concentration. The solvation time correlation function so calculated indeed
      displays strong composition dependent anomalies, reflected in pronounced non
      exponential kinetics and non-monotonous composition dependence of the average
      solvation time constant. In particular, we find remarkable slow-down in the
      solvation dynamics around 10%-20% and 35%-50% mole percentage. We investigate
      microscopic origin of these two anomalies. The population distribution analyses
      of different structural morphology elucidate that these two slowing down are
      reflections of intriguing structural transformations in water-DMSO mixture. The
      structural transformations themselves can be explained in terms of a change in
      the relative coordination number of DMSO and water molecules, from 1DMSO:2H2O to
      1H2O:1DMSO and 1H2O:2DMSO complex formation. Thus, while the emergence of first
      slow down (at 15% DMSO mole percentage) is due to the percolation among DMSO
      molecules supported by the water molecules (whose percolating network remains
      largely unaffected), the 2nd anomaly (centered on 40%-50%) is due to the
      formation of the network structure where the unit of 1DMSO:1H2O and 2DMSO:1H2O
      dominates to give rise to rich dynamical features. Through an analysis of partial
      solvation dynamics an interesting negative cross-correlation between water and
      DMSO is observed that makes an important contribution to relaxation at
      intermediate to longer times. 

PMID- 23883029
TI  - Ions colliding with clusters of fullerenes--decay pathways and covalent bond
      formations.
AB  - We report experimental results for the ionization and fragmentation of weakly
      bound van der Waals clusters of n C60 molecules following collisions with Ar(2+),
      He(2+), and Xe(20+) at laboratory kinetic energies of 13 keV, 22.5 keV, and 300
      keV, respectively. Intact singly charged C60 monomers are the dominant reaction
      products in all three cases and this is accounted for by means of Monte Carlo
      calculations of energy transfer processes and a simple Arrhenius-type [C60]n(+) 
      > C60(+)+(n-1)C60 evaporation model. Excitation energies in the range of only
      ~0.7 eV per C60 molecule in a [C60]13(+) cluster are sufficient for complete
      evaporation and such low energies correspond to ion trajectories far outside the
      clusters. Still we observe singly and even doubly charged intact cluster ions
      which stem from even more distant collisions. For penetrating collisions the
      clusters become multiply charged and some of the individual molecules may be
      promptly fragmented in direct knock-out processes leading to efficient formations
      of new covalent systems. For Ar(2+) and He(2+) collisions, we observe very
      efficient C119(+) and C118(+) formation and molecular dynamics simulations
      suggest that they are covalent dumb-bell systems due to bonding between C59(+) or
      C58(+) and C60 during cluster fragmentation. In the Ar(2+) case, it is possible
      to form even smaller C120-2m(+) molecules (m = 2-7), while no molecular fusion
      reactions are observed for the present Xe(20+) collisions.

PMID- 23883030
TI  - Selective bond breaking mediated by state specific vibrational excitation in
      model HOD molecule through optimized femtosecond IR pulse: a simulated annealing
      based approach.
AB  - The selective control of O-H/O-D bond dissociation in reduced dimensionality
      model of HOD molecule has been explored through IR+UV femtosecond pulses. The IR
      pulse has been optimized using simulated annealing stochastic approach to
      maximize population of a desired low quanta vibrational state. Since those
      vibrational wavefunctions of the ground electronic states are preferentially
      localized either along the O-H or O-D mode, the femtosecond UV pulse is used only
      to transfer vibrationally excited molecule to the repulsive upper surface to
      cleave specific bond, O-H or O-D. While transferring from the ground electronic
      state to the repulsive one, the optimization of the UV pulse is not necessarily
      required except specific case. The results so obtained are analyzed with respect
      to time integrated flux along with contours of time evolution of probability
      density on excited potential energy surface. After preferential excitation from
      [line]0, 0> ([line]m, n> stands for the state having m and n quanta of
      excitations in O-H and O-D mode, respectively) vibrational level of the ground
      electronic state to its specific low quanta vibrational state ([line]1, 0> or
      [line]0, 1> or [line]2, 0> or [line]0, 2>) by using optimized IR pulse, the
      dissociation of O-D or O-H bond through the excited potential energy surface by
      UV laser pulse appears quite high namely, 88% (O-H ; [line]1, 0>) or 58% (O-D ;
      [line]0, 1>) or 85% (O-H ; [line]2, 0>) or 59% (O-D ; [line]0, 2>). Such
      selectivity of the bond breaking by UV pulse (if required, optimized) together
      with optimized IR one is encouraging compared to the normal pulses.

PMID- 23883031
TI  - Ultrafast intramolecular relaxation dynamics of Mg- and Zn-bacteriochlorophyll a.
AB  - Ultrafast excited-state dynamics of the photosynthetic pigment (Mg
      )bacteriochlorophyll a and its Zn-substituted form were investigated by steady
      state absorption/fluorescence and femtosecond pump-probe spectroscopic
      measurements. The obtained steady-state absorption and fluorescence spectra of
      bacteriochlorophyll a in solution showed that the central metal compound
      significantly affects the energy of the Qx state, but has almost no effect on the
      Qy state. Photo-induced absorption spectra were recorded upon excitation of Mg-
      and Zn-bacteriochlorophyll a into either their Qx or Qy state. By comparing the
      kinetic traces of transient absorption, ground-state beaching, and stimulated
      emission after excitation to the Qx or Qy state, we showed that the Qx state was
      substantially incorporated in the ultrafast excited-state dynamics of
      bacteriochlorophyll a. Based on these observations, the lifetime of the Qx state
      was determined to be 50 and 70 fs for Mg- and Zn-bacteriochlorophyll a,
      respectively, indicating that the lifetime was influenced by the central metal
      atom due to the change of the energy gap between the Qx and Qy states. 

PMID- 23883032
TI  - A new six-dimensional potential energy surface for H2-N2O and its adiabatic
      hindered-rotor treatment.
AB  - A six-dimensional ab initio potential energy surface (PES) for H2-N2O which
      explicitly includes the symmetric and asymmetric vibrational coordinates Q1 and
      Q3 of N2O is calculated at the coupled-cluster singles and doubles with
      noniterative inclusion of connected triple level using an augmented correlation
      consistent polarized-valence quadruple-zeta basis set together with midpoint bond
      functions. Four-dimensional intermolecular PESs are then obtained by fitting the
      vibrationally averaged interactions energies for upsilon3(N2O) = 0 and 1 to the
      Morse/long-range analytical form. In the fits, fixing the long-range parameters
      at theoretical values smoothes over the numerical noise in the ab initio points
      in the long-range region of the potential. Using the adiabatic hindered-rotor
      approximation, two-dimensional PESs for hydrogen-N2O complexes with different
      isotopomers of hydrogen are generated by averaging the 4D PES over the rotation
      of the hydrogen molecule within the complex. The band-origin shifts for the
      hydrogen-N2O dimers calculated using both the 4D PESs and the angle-averaged 2D
      PESs are all in good agreement with each other and with the available
      experimental observations. The predicted infrared transition frequencies for para
      H2-N2O and ortho-D2-N2O are also consistent with the observed spectra. 

PMID- 23883033
TI  - Exchange narrowing and exciton delocalization in disordered J aggregates:
      simulated peak shapes in the two dimensional spectra.
AB  - Delocalized excitons in elementary linear J aggregates of two-level molecules
      absorb a photon into the low-energy edge of an exciton band. Absorption of a
      second photon is blue-shifted as the lowest energy state is occupied. This setup
      of states leads to a double-peak feature in a set of two dimensional photon echo
      spectra for excitonic bands. The delocalization properties of excitons, thus,
      strongly affect the peak lineshapes and their relative amplitudes. Simulations of
      various two dimensional spectra of a linear J aggregate are presented and
      possible schemes to quantitatively characterize the peak profiles are suggested.
      This allows to relate observable peak lineshapes to the exciton delocalization. 

PMID- 23883034
TI  - The spin and orbital moment of Fe(n) (n = 2-20) clusters.
AB  - Complementary to the recent experimental finding that the orbital magnetic moment
      is strongly quenched in small Fe clusters [M. Niemeyer, K. Hirsch, V. Zamudio
      Bayer, A. Langenberg, M. Vogel, M. Kossick, C. Ebrecht, K. Egashira, A. Terasaki,
      T. Moller, B. v. Issendorff, and J. T. Lau, Phys. Rev. Lett. 108, 057201 (2012)],
      we provide the theoretical understanding of the spin and orbital moments as well
      as the electronic properties of neutral and cation Fen clusters (n = 2-20) by
      taking into account the effects of strong electronic correlation, spin-orbit
      coupling, and noncollinearity of inter-atomic magnetization. The generalized
      gradient approximation (GGA)+U method is used and its effluence on the magnetic
      moment is emphasized. We find that without inclusion of the Coulomb interaction
      U, the spin (orbital) moments have an average value between 2.69 and 3.50
      MUB/atom (0.04 and 0.08 MUB/atom). With inclusion of U, the magnetic value is
      between 2.75 and 3.80 MUB/atom (0.10 and 0.30 MUB/atom), which provide an
      excellent agreement with the experimental measurements. Our results confirm that
      the spin moments are less quenched, while the orbital moments are strongly
      quenched in small Fe clusters. Both GGA and GGA+U functionals always yield
      collinear magnetic ground-state solutions for the fully relaxed Fe structures.
      Geometrical evolution, as a function of cluster size, illustrates that the
      icosahedral morphology competes with the hexagonal-antiprism morphology for large
      Fe clusters. In addition, the calculated trends of ionization potentials,
      electron affinities, fragment energies, and polarizabilities generally agree with
      respective experimental observations. 

PMID- 23883035
TI  - Photoelectron velocity-map imaging spectroscopic and theoretical study on the
      reactivity of the gold atom toward CH3SH, CH3OH, and H2O.
AB  - Photoelectron velocity-map imaging spectroscopy has been used to study the
      reaction of the anionic gold atom with the HR (R = SCH3, OCH3, OH) molecules. The
      solvated [Au...HR](-) and inserted [HAuR](-) products have been experimentally
      observed for R = SCH3, whereas only solvated [Au?HR](-) products were found for R
      = OCH3 and OH. This significant difference in the photoelectron spectra suggests
      the different reactivity of the Au(-) toward the CH3SH, CH3OH, and H2O molecules.
      Second order Moller-Plesset perturbation theory and coupled-cluster single double
      triple excitation calculations have been performed to aid the structural
      assignment of the spectra and to explore the reaction mechanism. Activation
      energies for the isomerizations of the solvated structures to the inserted ones
      in the Au(-)/Au + HR reactions (R = OCH3 and OH) are predicted to be much higher
      than those for the Au(-)/Au + CH3SH reactions, supporting the experimental
      observation. Theoretical calculations provide the evidence that the intriguing
      [HAuSCH3](-) product may be formed by the attachment of the electron onto the
      neutral HAuSCH3 species or the isomerization from the anionic [Au...HSCH3](-)
      one. These findings should be helpful for understanding the feature that the
      thiols are able to form the staple motifs, whereas CH3OH and H2O are not.

PMID- 23883036
TI  - Following the relaxation dynamics of photoexcited aniline in the 273-266 nm
      region using time-resolved photoelectron imaging.
AB  - Time-resolved photoelectron imaging was used to investigate the relaxation
      dynamics of electronically excited aniline in the gas-phase following ultraviolet
      irradiation in the 273-266 nm region. We find that at all wavelengths studied,
      excitation is predominantly to the long-lived (>1 ns) S1(pipi(*)) state, which
      exhibits ultrafast intramolecular vibrational redistribution on a <1 ps
      timescale. At excitation wavelengths centred on resonant transitions in the
      aniline absorption spectrum that have previously been assigned to the higher
      lying S2(3s/pisigma(*)) state, we also see clear evidence of this state playing a
      role in the dynamics. However, we see no indication of any non-adiabatic coupling
      between the S1(pipi(*)) and S2(3s/pisigma(*)) states over the range of excitation
      wavelengths studied.

PMID- 23883037
TI  - Investigation of oxygen dissociation and vibrational relaxation at temperatures
      4000-10,800 K.
AB  - The oxygen absorbance was studied at wavelengths 200-270 nm in Schumann-Runge
      system behind the front of a strong shock wave. Using these data, the vibrational
      temperature Tv behind the front of shock waves was measured at temperatures 4000
      10,800 K in undiluted oxygen. Determination of Tv was based on the measurements
      of time histories of absorbance for two wavelengths behind the shock front and on
      the results of detail calculations of oxygen absorption spectrum. Solving the
      system of standard quasi-one-dimensional gas dynamics equations and using the
      measured vibrational temperature, the time evolution of oxygen concentration and
      other gas parameters in each experiment were calculated. Based on these data, the
      oxygen dissociation rate constants were obtained for thermal equilibrium and
      thermal non-equilibrium conditions. Furthermore, the oxygen vibrational
      relaxation time was also determined at high temperatures. Using the experimental
      data, various theoretical and empirical models of high-temperature dissociation
      were tested, including the empirical model proposed in the present work.

PMID- 23883038
TI  - Timescales for adiabatic photodissociation dynamics from the A state of ammonia.
AB  - Photodissociation dynamics after excitation of the A state nu'2 = 4 (umbrella)
      level of ammonia are investigated using ultrafast time-resolved velocity map ion
      imaging (TR-VMI). These studies extend upon previous TR-VMI measurements [K. L.
      Wells, G. Perriam, and V. G. Stavros, J. Chem. Phys. 130, 074308 (2009)], which
      reported the appearance timescales for ground state NH2(X)+H photoproducts, born
      from non-adiabatic passage through an X/A state conical intersection (CI) at
      elongated H-NH2 bond distances. In particular, the present work sheds new light
      on the formation timescales for electronically excited NH2(A)+H species,
      generated from NH3 parent molecules that avoid the CI and dissociate
      adiabatically. The results reveal a step-wise dynamical picture for the
      production of NH2(A)+H products, where nascent dissociative flux can become
      temporarily trapped/impeded around the upper cone of the CI on the A state
      potential energy surface (PES), while on course towards the adiabatic
      dissociation asymptote - this behavior contrasts the concerted mechanism
      previously observed for non-adiabatic dissociation into H-atoms associated with
      ro-vibrationally "cold" NH2(X). Initially, non-planar NH3 molecules (species
      which have the capacity to yield adiabatic photoproducts) are found to evolve out
      of the vertical Franck-Condon excitation region and towards the CI region of the
      A state PES with a time-constant of 113 +/- 46 fs. Subsequently, transient
      population encircling the CI then progresses to finally form NH2(A)+H
      photoproducts from the CI region of the A state PES with a slower time-constant
      of 415 +/- 25 fs. Non-adiabatic dissociation into ro-vibrationally "hot" NH2(X)
      radicals together with H-atoms is also evidenced to occur via a qualitatively
      similar process. 

PMID- 23883039
TI  - A first principles study of thiol-capped Au nanoparticles: structural,
      electronic, and magnetic properties as a function of thiol coverage.
AB  - We have studied the stability of thiolated Au38 nanoparticles (NPs) via density
      functional theory based calculations varying the coverage from 0 up to 32
      molecules. Three different initial core arrangements were considered for the
      cluster, spherical, tubular, and bi-icosahedral, while thiol groups were attached
      to the cluster via the sulfur atom either as single molecules or forming more
      complex staple motifs. After molecular dynamics runs several metastable
      configurations are found at each coverage thus allowing to analyze the properties
      of the NPs in the form of ensemble averages. In particular, we address the
      structural and electronic properties as a function of the number of thiols. The
      study emphasizes the strong influence of the core structure on the stability of
      the NPs, and its interplay with the thiol coverage and adsorption geometries. The
      magnetic properties of the NPs have also been explored via spin-polarized
      calculations including spin-orbit coupling. No evidence for the existence of a
      robust intrinsic ferromagnetism is found in any of the structures. 

PMID- 23883040
TI  - Effects of a remote binding partner on the electric field and electric field
      gradient at an atom in a weakly bound trimer.
AB  - Microwave spectra are reported for the C3v symmetric complexes Kr-SO3 and Kr-SO3
      CO. The S-C distance in the trimer, 2.871(9) A, is the same as that previously
      determined for SO3-CO to within the estimated uncertainties. The Kr-S distances
      are 3.438(3) A and 3.488(6) A in Kr-SO3 and Kr-SO3-CO, respectively, indicating
      that the addition of CO to Kr-SO3 increases the Kr-S distance by 0.050(9) A.
      Measurements of the (83)Kr nuclear quadrupole coupling constants provide direct
      probes of the electric field gradient at the Kr nucleus, and a comparison between
      the two systems reflects the degree to which the CO influences the electronic
      structure of the krypton atom. Although the Kr and CO in the trimer are on
      opposite sides of the SO3 and thus are not in direct contact, the addition of CO
      to Kr-SO3 reduces the electric field gradient at the Kr nucleus by 18%.
      Calculations using the block localized wavefunction decomposition method are
      performed to understand the physical origins of this change. While the magnitudes
      of both the electric field and the electric field gradient at the Kr nucleus
      decrease upon addition of the CO to Kr-SO3, the changes are shown to arise from
      rather complex combinations of geometrical distortion, electrostatic,
      polarization, and electron transfer effects. For the electric field, the
      electrostatic term accounts for the largest portion of the reduction, while for
      the electric field gradient, polarization and structural change of the Kr-SO3
      moiety make the primary contributions. Despite significant changes in the
      electronic environment at the Kr nucleus, calculated binding energies indicate
      that the interactions are largely additive, with the binding energy of the trimer
      very nearly equal to the sum of the Kr-SO3 and SO3-CO binding energies. 

PMID- 23883041
TI  - How does the isomerization rate affect the photoisomerization-induced transport
      properties of a doped molecular glass-former?
AB  - We investigate the effect of the isomerization rate f on the microscopic
      mechanisms at the origin of the massive mass transport found in glass-formers
      doped with isomerizing azobenzene molecules that result in surface relief
      gratings formation. To this end we simulate the isomerization of dispersed probe
      molecules embedded into a molecular host glass-former. The host diffusion
      coefficient first increases linearly with f and then saturates. The saturated
      value of the diffusion coefficient and of the viscosity does not depend on f but
      increases with temperature while the linear response for these transport
      coefficients depends only slightly on the temperature. We interpret this
      saturation as arising from the appearance of increasingly soft regions around the
      probes for high isomerization rates, a result in qualitative agreement with
      experiments. These two different physical behaviors, linear response and
      saturation, are reminiscent of the two different unexplained mass transport
      mechanisms observed for small or large light intensities (for small intensities
      the molecules move towards the dark regions while for large intensities they move
      towards the illuminated regions). 

PMID- 23883042
TI  - A joint theoretical/experimental study of the structure, dynamics, and Li+
      transport in bis([tri]fluoro[methane]sulfonyl)imide [T]FSI-based ionic liquids.
AB  - The structure and dynamics of N-butyl-N-methyl pyrrolidinium(+)
      bis([tri]fluoro[methane]sulfonyl)imide(-) (PYR14(+)-[T]FSI(-)) ionic liquids
      doped with Li(T)FSI are investigated by combining experimental measurements to
      molecular dynamics simulations. The polarizable force field calculations indicate
      that the lithium cations are coordinated by (T)FSI anion oxygens forming lithium
      adducts stabilized over a large temperature range by strong Li-O bonds. Lithium
      aggregation is found to be negligible at the doping level considered here (10%
      mole fraction), and Li(+) diffusion occurs primarily by exchanging the (T)FSI
      anions in their first coordination shell. The resulting calculated transport
      properties are in good agreement with the corresponding nuclear magnetic
      resonance data.

PMID- 23883043
TI  - Accurate evaluation of the angular-dependent direct correlation function of
      water.
AB  - The direct correlation function (DCF) plays a pivotal role in addressing the
      thermodynamic properties with non-mean-field statistical theories of liquid
      state. This work provides an accurate yet efficient calculation procedure for
      evaluating the angular-dependent DCF of bulk SPC/E water. The DCF here
      represented in a discrete angles basis is computed with two typical steps: the
      first step involves solving the molecular Ornstein-Zernike equation with the
      input of total correlation function extracted from simulation; the resultant DCF
      is then polished in second step at small wavelength for all orientations in order
      to match correct thermodynamic properties. This function is also discussed in
      terms of its rotational invariant components. In particular, we show that the
      component c112(r) that accounts for dipolar symmetry reaches already its long
      range asymptotic behavior at a short distance of 4 A. With the knowledge of DCF,
      the angular-dependent bridge function of bulk water is thereafter computed and
      discussed in comparison with referenced hard-sphere bridge functions. We conclude
      that, even though such hard-sphere bridge functions may be relevant to improve
      the calculation of Helmholtz free energies in integral equations or density
      functional theory, they are doomed to fail at a structural level. 

PMID- 23883045
TI  - The isotropic-nematic phase transition of tangent hard-sphere chain fluids--pure
      components.
AB  - An extension of Onsager's second virial theory is developed to describe the
      isotropic-nematic phase transition of tangent hard-sphere chain fluids.
      Flexibility is introduced by the rod-coil model. The effect of chain-flexibility
      on the second virial coefficient is described using an accurate, analytical
      approximation for the orientation-dependent pair-excluded volume. The use of this
      approximation allows for an analytical treatment of intramolecular flexibility by
      using a single pure-component parameter. Two approaches to approximate the effect
      of the higher virial coefficients are considered, i.e., the Vega-Lago rescaling
      and Scaled Particle Theory (SPT). The Onsager trial function is employed to
      describe the orientational distribution function. Theoretical predictions for the
      equation of state and orientational order parameter are tested against the
      results from Monte Carlo (MC) simulations. For linear chains of length 9 and
      longer, theoretical results are in excellent agreement with MC data. For smaller
      chain lengths, small errors introduced by the approximation of the higher virial
      coefficients become apparent, leading to a small under- and overestimation of the
      pressure and density difference at the phase transition, respectively. For rod
      coil fluids of reasonable rigidity, a quantitative comparison between theory and
      MC simulations is obtained. For more flexible chains, however, both the Vega-Lago
      rescaling and SPT lead to a small underestimation of the location of the phase
      transition. 

PMID- 23883044
TI  - Interactions of S-peptide analogue in aqueous urea and trimethylamine-N-oxide
      solutions: a molecular dynamics simulation study.
AB  - The ability of the osmolyte, trimethylamine-N-oxide (TMAO), to protect proteins
      from deleterious effect of urea, another commonly available osmolyte, is well
      established. However, the molecular mechanism of this counteraction is not
      understood yet. To provide a molecular level understanding of how TMAO protects
      proteins in highly concentrated urea solution, we report here molecular dynamics
      simulation results of a 15-residue model peptide in two different conformations:
      helix and extended. For both conformations, simulations are carried out in pure
      water as well as in binary and ternary aqueous solutions of urea and TMAO.
      Analysis of solvation characteristics reveals direct interactions of urea and
      TMAO with peptide residues. However, the number of TMAO molecules that enter in
      the first solvation shell of the peptide is significantly lower than that of
      urea, and, unlike water and urea, TMAO shows its inability to form hydrogen bond
      with backbone oxygen and negatively charged sidechains. Preferential accumulation
      of urea near the peptide surface and preferential exclusion of TMAO from the
      peptide surface are observed. Inclusion of osmolytes in the peptide solvation
      shell leads to dehydration of the peptide in binary and ternary solutions of urea
      and TMAO. Solvation of peptide residues are investigated more closely by
      calculating the number of hydrogen bonds between the peptide and solution
      species. It is found that number of hydrogen bonds formed by the peptide with
      solution species increases in binary urea solution (relative to pure water) and
      this relative enhancement in hydrogen bond number reduces upon addition of TMAO.
      Our simulation results also suggest that, in the ternary solution, the peptide
      solvation layer is better mixed in terms of water and urea as compared to binary
      urea solution. Implications of the results for counteraction mechanism of TMAO
      are discussed. 

PMID- 23883046
TI  - Electronic structure differences between H(2)-, Fe-, Co-, and Cu-phthalocyanine
      highly oriented thin films observed using NEXAFS spectroscopy.
AB  - Phthalocyanines, a class of macrocyclic, square planar molecules, are extensively
      studied as semiconductor materials for chemical sensors, dye-sensitized solar
      cells, and other applications. In this study, we use angular dependent near-edge
      x-ray absorption fine structure (NEXAFS) spectroscopy as a quantitative probe of
      the orientation and electronic structure of H2-, Fe-, Co-, and Cu-phthalocyanine
      molecular thin films. NEXAFS measurements at both the carbon and nitrogen K-edges
      reveal that phthalocyanine films deposited on sapphire have upright molecular
      orientations, while films up to 50 nm thick deposited on gold substrates contain
      prostrate molecules. Although great similarity is observed in the carbon and
      nitrogen K-edge NEXAFS spectra recorded for the films composed of prostrate
      molecules, the H2-phthalocyanine exhibits the cleanest angular dependence due to
      its purely out-of-plane pi* resonances at the absorption onset. In contrast,
      organometallic-phthalocyanine nitrogen K-edges have a small in-plane resonance
      superimposed on this pi* region that is due to a transition into molecular
      orbitals interacting with the 3dx(2)-y(2) empty state. NEXAFS spectra recorded at
      the metal L-edges for the prostrate films reveal dramatic variations in the
      angular dependence of specific resonances for the Cu-phthalocyanines compared
      with the Fe-, and Co-phthalocyanines. The Cu L3,2 edge exhibits a strong in-plane
      resonance, attributed to its b1g empty state with dx(2)-y(2) character at the Cu
      center. Conversely, the Fe- and Co- phthalocyanine L3,2 edges have strong out-of
      plane resonances; these are attributed to transitions into not only b1g (dz(2))
      but also eg states with dxz and dyz character at the metal center.

PMID- 23883047
TI  - Temperature of critical clusters in nucleation theory: generalized Gibbs'
      approach.
AB  - According to the classical Gibbs' approach to the description of
      thermodynamically heterogeneous systems, the temperature of the critical clusters
      in nucleation is the same as the temperature of the ambient phase, i.e., with
      respect to temperature the conventional macroscopic equilibrium conditions are
      assumed to be fulfilled. In contrast, the generalized Gibbs' approach [J. W. P.
      Schmelzer, G. Sh. Boltachev, and V. G. Baidakov, J. Chem. Phys. 119, 6166 (2003);
      and ibid. 124, 194503 (2006)] predicts that critical clusters (having commonly
      spatial dimensions in the nanometer range) have, as a rule, a different
      temperature as compared with the ambient phase. The existence of a curved
      interface may lead, consequently, to an equilibrium coexistence of different
      phases with different temperatures similar to differences in pressure as
      expressed by the well-known Laplace equation. Employing the generalized Gibbs'
      approach, it is demonstrated that, for the case of formation of droplets in a one
      component vapor, the temperature of the critical droplets can be shown to be
      higher as compared to the vapor. In this way, temperature differences between
      critically sized droplets and ambient vapor phase, observed in recent molecular
      dynamics simulations of argon condensation by Wedekind et al. [J. Chem. Phys.
      127, 064501 (2007)], can be given a straightforward theoretical interpretation.
      It is shown as well that - employing the same model assumptions concerning bulk
      and interfacial properties of the system under consideration - the temperature of
      critical bubbles in boiling is lower as compared to the bulk liquid. 

PMID- 23883048
TI  - New direct method for evaluating recoilless f-factors of two iron-sites in Fe
      bearing compounds using Mossbauer spectrometry.
AB  - We propose a new direct method for calculating simultaneously two recoilless f
      factors of any iron-bearing compound relative to that of a reference material by
      collecting only a single-temperature Mossbauer spectrum. This methodology is
      comparatively much simpler than the usual one which requires taking Mossbauer
      spectra of the compound at several temperatures and subsequently fitting the
      temperature dependence of the subspectral area or the isomer shift data with a
      lattice vibrational model. We demonstrate the applicability of this new
      methodology in the case of three common iron-bearing compounds: magnetite,
      akaganeite and goethite, but of course this type of study can be extended to
      other materials. The two f-factors for each compound were related to iron ions
      located in sites of different origin: for magnetite, these were related to irons
      with two different oxidation states; for akaganeite to irons in two different
      crystallographic sites; and for goethite to irons in similar crystal sites but
      located in grains of different sizes. In the case of magnetite, we found that the
      f-factors for the Fe(3+) and Fe(2.5+) sites relative to that of metallic iron
      powder were of fFe (3+)/fFe = 0.97 +/- 0.05 and fFe (2.5+)/fFe = 0.92 +/- 0.05,
      respectively. Interestingly, the quotient of these two f-factors, i.e., fFe
      (2.5+)/fFe (3+), is equal to 0.95 +/- 0.05, which compares fairly well with a
      value reported in literature obtained using the complex methodology based on the
      temperature dependence of the absolute subspectral area and the Debye
      approximation. For akaganeite, the f-factors of the doublet 1, D1, and doublet 2,
      D2, sites relative to that of metallic iron powder were of fD 1/fFe = 0.95 +/-
      0.08 and fD 2/fFe = 0.98 +/- 0.15, respectively. And for goethite we found that
      the f-factors of the sextet 1, G1, and sextet 2, G2, sites relative to that of
      metallic iron powder were of fG 1/fFe = 0.80 +/- 0.02 and fG 2/fFe = 0.80 +/-
      0.02, respectively. The similarity of these last two factors is perhaps due to a
      sharp distribution of large grains. 

PMID- 23883049
TI  - Non-hexagonal symmetry-induced functional T graphene for the detection of carbon
      monoxide.
AB  - Unlike on hexagonal graphene where Li atoms tend to cluster, using density
      functional theory, we demonstrate that Li atoms remain isolated on
      tetrasymmetrical T graphene due to a nonuniform charge distribution in T
      graphene. Furthermore, we examine the adsorption of several common gas molecules
      and find that Li-decorated T graphene exhibits a high sensitivity to CO. The CO
      adsorption strength can be manipulated by an external electric field, resulting
      in a short recovery time. Our results provide an insight to build promising
      nanosensors based on two-dimensional carbonic materials beyond hexagonal
      symmetry. 

PMID- 23883050
TI  - Catalytic micromotor generating self-propelled regular motion through random
      fluctuation.
AB  - Most of the current studies on nano/microscale motors to generate regular motion
      have adapted the strategy to fabricate a composite with different materials. In
      this paper, we report that a simple object solely made of platinum generates
      regular motion driven by a catalytic chemical reaction with hydrogen peroxide.
      Depending on the morphological symmetry of the catalytic particles, a rich
      variety of random and regular motions are observed. The experimental trend is
      well reproduced by a simple theoretical model by taking into account of the
      anisotropic viscous effect on the self-propelled active Brownian fluctuation. 

PMID- 23883051
TI  - Consistent coarse-graining strategy for polymer solutions in the thermal
      crossover from good to theta solvent.
AB  - We extend our previously developed coarse-graining strategy for linear polymers
      with a tunable number n of effective atoms (blobs) per chain [G. D'Adamo et al.,
      J. Chem. Phys. 137, 024901 (2012)] to polymer systems in thermal crossover
      between the good-solvent and the theta regimes. We consider the thermal crossover
      in the region in which tricritical effects can be neglected, i.e., not too close
      to the theta point, for a wide range of chain volume fractions Phi = c/c* (c* is
      the overlap concentration), up to Phi ~ 30. Scaling crossover functions for
      global properties of the solution are obtained by Monte Carlo simulations of the
      Domb-Joyce model with suitably rescaled on-site repulsion. They provide the input
      data to develop a minimal coarse-grained model with four blobs per chain
      (tetramer model). As in the good-solvent case, the coarse-grained model
      potentials are derived at zero density, thus avoiding the inconsistencies related
      to the use of state-dependent potentials. We find that the coarse-grained model
      reproduces the properties of the underlying, full-monomer system up to some
      reduced density Phi which increases when lowering the temperature towards the
      theta state. Close to the lower-temperature crossover boundary, the tetramer
      model is accurate at least up to Phi ~/= 10, while near the good-solvent regime
      reasonably accurate results are obtained up to Phi ~/= 2. The density region in
      which the coarse-grained model is predictive can be enlarged by developing coarse
      grained models with more blobs per chain. We extend the strategy used in the good
      solvent case to the crossover regime. This requires a proper treatment of the
      length rescalings as before, but also a proper temperature redefinition as the
      number of blobs is increased. The case n = 10 is investigated in detail. We
      obtain the potentials for such finer-grained model starting from the tetramer
      ones. Comparison with full-monomer results shows that the density region in which
      accurate predictions can be obtained is significantly wider than that
      corresponding to the tetramer case.

PMID- 23883052
TI  - Interpretation of quasielastic scattering spectra of probe species in complex
      fluids.
AB  - The objective of this paper is to correct an error in analyses of quasielastic
      scattering spectra. The error invokes a valid calculation under conditions in
      which its primary assumptions are incorrect, which results in misleading
      interpretations of spectra. Quasielastic scattering from dilute probes yields the
      incoherent structure factor g((1s))(q, t) = <exp (iqDeltax(t))>, with q being the
      magnitude of the scattering vector q and Deltax(t) being the probe displacement
      parallel to q during a time interval t. The error is a claim that g((1s))(q, t) ~
      exp (-q(2)<(Deltax(t))(2)>/2) for probes in an arbitrary solution, leading to the
      incorrect belief that <(Deltax(t))(2)> of probes in complex fluids can be
      inferred from quasielastic scattering. The actual theoretical result refers only
      to monodisperse probes in simple Newtonian liquids. In general, g((1s))(q, t) is
      determined by all even moments <(Deltax(t))(2n)>, n = 1, 2, 3, ... of the
      displacement distribution function P(Deltax, t). Correspondingly,
      <(Deltax(t))(2)> cannot in general be inferred from g((1s)) (q, t). The
      theoretical model that ties g((1s))(q, t) to <(Deltax(t))(2)> also quantitatively
      determines exactly how <(Deltax(t))(2)>/2) must behave, namely, <(Deltax(t))(2)>
      must increase linearly with t. If the spectrum is not a single exponential in
      time, g((1s))(q, t) does not determine <(Deltax(t))(2)>.

PMID- 23883053
TI  - Controlling adsorption of semiflexible polymers on planar and curved substrates.
AB  - We study the adsorption of semiflexible polymers such as polyelectrolytes or DNA
      on planar and curved substrates, e.g., spheres or washboard substrates via short
      range potentials using extensive Monte Carlo simulations, scaling arguments, and
      analytical transfer matrix techniques. We show that the adsorption threshold of
      stiff or semiflexible polymers on a planar substrate can be controlled by polymer
      stiffness: adsorption requires the highest potential strength if the persistence
      length of the polymer matches the range of the adsorption potential. On curved
      substrates, i.e., an adsorbing sphere or an adsorbing washboard surface, the
      adsorption can be additionally controlled by the curvature of the surface
      structure. The additional bending energy in the adsorbed state leads to an
      increase of the critical adsorption strength, which depends on the curvature
      radii of the substrate structure. For an adsorbing sphere, this gives rise to an
      optimal polymer stiffness for adsorption, i.e., a local minimum in the critical
      potential strength for adsorption, which can be controlled by curvature. For two-
      and three-dimensional washboard substrates, we identify the range of persistence
      lengths and the mechanisms for an effective control of the adsorption threshold
      by the substrate curvature. 

PMID- 23883054
TI  - Molecular dynamics of polyisoprene/polystyrene oligomer blends: the role of self
      concentration and fluctuations on blend dynamics.
AB  - The effect of self-concentration and intermolecular packing on the dynamics of
      polyisoprene (PI)/polystyrene (PS) blends is examined by extensive atomistic
      simulations. Direct information on local structure of the blend system allows a
      quantitative calculation of self- and effective composition terms at various
      length scales that are introduced to proposed models of blend dynamics. Through a
      detailed statistical analysis, the full distribution of relaxation times
      associated with reorienation of carbon-hydrogen bonds was extracted and compared
      to literature experimental data. A direct relation between relaxation times and
      local effective composition is found. Following an implementation of a model
      involving local composition as well as concentration fluctuations the relevant
      length scales characterizing the segmental dynamics of both components were
      critically examined. For PI, the distribution of times becomes narrower for the
      system with the lowest PS content and then broadens as more PS is added. This is
      in contrast to the slow component (PS), where an extreme breadth is found for
      relaxation times in the 25/75 system prior to narrowing as we increase PI
      concentration. The chain dynamics was directly quantified by diffusion
      coefficients as well as the terminal (maximum) relaxation time of each component
      in the mixed state. Strong coupling between the friction coefficients of the two
      components was predicted that leads to very similar chain dynamics for PI and PS,
      particularly for high concentrations of PI. We attribute this finding to the
      rather short oligomers (below the Rouse regime) studied here as well as to the
      rather similar size of PI and PS chains. The ratio of the terminal to the
      segmental relaxation time, tauterm/tauseg, c, presents a clear qualitative
      difference for the constituents: for PS the above ratio is almost independent of
      blend composition and very similar to the pure state. In contrast, for PI this
      ratio depends strongly on the composition of the blend; i.e., the terminal
      relaxation time of PI increases more than its segmental relaxation time, as the
      concentration of PS increases, resulting into a larger terminal/segmental ratio.
      We explain this disparity based on the different length scales characterizing
      dynamics. The relevant length for the segmental dynamics of PI is about 0.4-0.6
      nm, smaller than chain dimensions which are expected to characterize terminal
      dynamics, whereas for PS associated length scales are similar (about 0.7-1.0 nm)
      rendering a uniform change with mixing. 

PMID- 23883056
TI  - Consensus for the Fip35 folding mechanism?
AB  - Recent advances in computational power and simulation programs finally delivered
      the first examples of reversible folding for small proteins with an all-atom
      description. But having at hand the atomistic details of the process did not lead
      to a straightforward interpretation of the mechanism. For the case of the Fip35
      WW-domain where multiple long trajectories of 100 MUs are available from D. E.
      Shaw Research, different interpretations emerged. Some of those are in clear
      contradiction with each other while others are in qualitative agreement. Here, we
      present a network-based analysis of the same data by looking at the local
      fluctuations of conventional order parameters for folding. We found that folding
      occurs through two major pathways, one almost four times more populated than the
      other. Each pathway involves the formation of an intermediate with one of the two
      hairpins in a native configuration. The quantitative agreement of our results
      with a state-of-the-art reaction coordinate optimization procedure as well as
      qualitative agreement with other Markov-state-models and different simulation
      schemes provides strong evidence for a multiple folding pathways scenario with
      the presence of intermediates. 

PMID- 23883057
TI  - Parallel Cascade Selection Molecular Dynamics (PaCS-MD) to generate
      conformational transition pathway.
AB  - Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a
      molecular simulation method to generate conformational transition pathway under
      the condition that a set of "reactant" and "product" structures is known a
      priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics
      simulations and selection of the structures close to the product structure for
      the next cycle are repeated until the simulated structures move sufficiently
      close to the product. Folding of 10-residue mini-protein chignolin from the
      extended to native structures and open-close conformational transition of T4
      lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD
      were sufficient to reach the product structures, indicating the efficient
      generation of conformational transition pathway in PaCS-MD with a series of
      conventional MD without additional external biases. Using the snapshots along the
      pathway as the initial coordinates, free energy landscapes were calculated by the
      combination with multiple independent umbrella samplings to statistically
      elucidate the conformational transition pathways. 

PMID- 23883055
TI  - Identification of small-molecule binding pockets in the soluble monomeric form of
      the Abeta42 peptide.
AB  - The aggregation of intrinsically disordered peptides and proteins is associated
      with a wide range of highly debilitating neurological and systemic disorders. In
      this work we explored the potential of a structure-based drug discovery procedure
      to target one such system, the soluble monomeric form of the Abeta42 peptide. We
      utilised for this purpose a set of structures of the Abeta42 peptide selected
      from clusters of conformations within an ensemble generated by molecular dynamics
      simulations. Using these structures we carried out fragment mapping calculations
      to identify binding "hot spots" on the monomeric form of the Abeta42 peptide.
      This procedure provided a set of hot spots with ligand efficiencies comparable to
      those observed for structured proteins, and clustered into binding pockets. Such
      binding pockets exhibited a propensity to bind small molecules known to interact
      with the Abeta42 peptide. Taken together these results provide an initial
      indication that fragment-based drug discovery may represent a potential
      therapeutic strategy for diseases associated with the aggregation of
      intrinsically disordered proteins. 

PMID- 23883058
TI  - Cation-cation contact pairing in water: guanidinium.
AB  - The formation of like-charge guanidinium-guanidinium contact ion pairs in water
      is evidenced and characterized by X-ray absorption spectroscopy and first
      principles spectral simulations based on molecular dynamics sampling. Observed
      concentration-induced nitrogen K-edge resonance shifts result from pi* state
      mixing and the release of water molecules from each first solvation sphere as two
      solvated guanidinium ions associate into a stacked pair configuration. Possible
      biological implications of this counterintuitive cation-cation pairing are
      discussed.

PMID- 23883059
TI  - Directional fidelity of nanoscale motors and particles is limited by the 2nd law
      of thermodynamics--via a universal equality.
AB  - Directional motion of nanoscale motors and driven particles in an isothermal
      environment costs a finite amount of energy despite zero work as decreed by the
      2nd law, but quantifying this general limit remains difficult. Here we derive a
      universal equality linking directional fidelity of an arbitrary nanoscale object
      to the least possible energy driving it. The fidelity-energy equality depends on
      the environmental temperature alone; any lower energy would violate the 2nd law
      in a thought experiment. Real experimental proof for the equality comes from
      force-induced motion of biological nanomotors by three independent groups - for
      translational as well as rotational motion. Interestingly, the natural self
      propelled motion of a biological nanomotor (F1-ATPase) known to have nearly 100%
      energy efficiency evidently pays the 2nd law decreed least energy cost for
      direction production. 

PMID- 23883060
TI  - Note: thermorheological complexity in polymers and the problem of the glass
      transition.

PMID- 23883061
TI  - Note: recombination of H+ and OH- ions along water wires.

PMID- 23883066
TI  - Activation of rhenium(I) toward substitution in fac-[Re(N,O'-Bid)(CO)3(HOCH3)] by
      Schiff-base bidentate ligands (N,O'-Bid).
AB  - A series of fac-[Re(N,O'-Bid)(CO)3(L)] (N,O'-Bid = monoanionic bidentate Schiff
      base ligands with N,O donor atoms; L = neutral monodentate ligand) has been
      synthesized, and the methanol substitution reactions have been investigated. The
      complexes were characterized by NMR, IR, and UV-vis spectroscopy. X-ray crystal
      structures of the compounds fac-[Re(Sal-mTol)(CO)3(HOCH3)], fac-[Re(Sal
      pTol)(CO)3(HOCH3)], fac-[Re(Sal-Ph)(CO)3(HOCH3)], and fac-[Re(Sal-Ph)(CO)3(Py)]
      (Sal-mTol = 2-(m-tolyliminomethyl)phenolato; Sal-pTol = 2-(p
      tolyliminomethyl)phenolato; Sal-Ph = 2-(phenyliminomethyl)phenolato; Py =
      pyridine) are reported. Significant activation for the methanol substitution is
      induced by the use of the N,O bidentate ligand as manifested by the second order
      rate constants, with limiting kinetics being observed for the first time. Rate
      constants (25  degrees C) (k1 or k3) and activation parameters (DeltaHk?, kJ mol(
      1); DeltaSk?, J K(-1) mol(-1)) from Eyring plots for entering nucleophiles as
      indicated are as follows: fac-[Re(Sal-mTol)(CO)3(HOCH3)] 3-chloropyridine: (k1)
      2.33 +/- 0.01 M(-1) s(-1); 85.1 +/- 0.6, 48 +/- 2; fac-[Re(Sal-mTol)(CO)3(HOCH3)]
      pyridine: (k1) 1.29 +/- 0.02 M(-1) s(-1); 92 +/- 2, 66 +/- 7; fac-[Re(Sal
      mTol)(CO)3(HOCH3)] 4-picoline: (k1) 1.27 +/- 0.05 M(-1) s(-1); 88 +/- 2, 53 +/-
      6; (k3) 3.9 +/- 0.03 s(-1); 78 +/- 8, 30 +/- 27; (kf) 1.7 +/- 0.02 M(-1) s(-1);
      86 +/- 2, 49 +/- 6; fac-[Re(Sal-mTol)(CO)3(HOCH3)] DMAP (k3) 1.15 +/- 0.02 s(-1);
      88 +/- 2, 52 +/- 7. An interchange dissociative mechanism is proposed.

PMID- 23883065
TI  - Oncogenic transformation of mammary epithelial cells by transforming growth
      factor beta independent of mammary stem cell regulation.
AB  - BACKGROUND: Transforming growth factor beta (TGFbeta) is transiently increased in
      the mammary gland during involution and by radiation. While TGFbeta normally has
      a tumour suppressor role, prolonged exposure to TGFbeta can induce an oncogenic
      epithelial to mesenchymal transition (EMT) program in permissive cells and
      initiate the generation of cancer stem cells. Our objective is to mimic the
      transient exposure to TGFbeta during involution to determine the persistent
      effects on premalignant mammary epithelium. METHOD: CDbetaGeo cells, a
      transplantable mouse mammary epithelial cell line, were treated in vitro for 14
      days with TGFbeta (5 ng/ml). The cells were passaged for an additional 14 days in
      media without TGFbeta and then assessed for markers of EMT and transformation.
      RESULTS: The 14-day exposure to TGFbeta induced EMT and transdifferentiation in
      vitro that persists after withdrawal of TGFbeta. TGFbeta-treated cells are highly
      tumorigenic in vivo, producing invasive solid de-differentiated tumours (100%;
      latency 6.7 weeks) compared to control (43%; latency 32.7 weeks). Although the
      TGFbeta-treated cells have initiated a persistent EMT program, the stem cell
      population was unchanged relative to the controls. The gene expression profiles
      of TGFbeta-treated cells demonstrate de-differentiation with decreases in the
      expression of genes that define luminal, basal and stem cells. Additionally, the
      gene expression profiles demonstrate increases in markers of EMT, growth factor
      signalling, TGFbeta2 and changes in extra cellular matrix. CONCLUSION: This model
      demonstrates full oncogenic EMT without an increase in stem cells, serving to
      separate EMT markers from stem cell markers.

PMID- 23883067
TI  - Evaluation of a carbonic anhydrase mimic for industrial carbon capture.
AB  - Zinc(II) cyclen, a small molecule mimic of the enzyme carbonic anhydrase, was
      evaluated under rigorous conditions resembling those in an industrial carbon
      capture process: high pH (>12), nearly saturated salt concentrations (45% K2CO3)
      and elevated temperatures (100-130  degrees C). We found that the catalytic
      activity of zinc cyclen increased with increasing temperature and pH and was
      retained after exposure to a 45% w/w K2CO3 solution at 130  degrees C for 6 days.
      However, high bicarbonate concentrations markedly reduced the activity of the
      catalyst. Our results establish a benchmark level of stability and provide
      qualitative insights for the design of improved small-molecule carbon capture
      catalysts. 

PMID- 23883068
TI  - Diagnostic accuracy and clinical application of faecal calprotectin in adult
      patients presenting with gastrointestinal symptoms in primary care.
AB  - OBJECTIVE: Assessment of faecal calprotectin (fCal) test performance in primary
      care within an irritable bowel syndrome (IBS) diagnostic pathway. METHODS: Study
      based on consecutively collected fCal data from 962 patients, aged 18-45,
      presenting to their general practitioner (GP) with persistent gastrointestinal
      symptoms. RESULTS: Six hundred and eighty six (71%) patients had a negative (<50
      MUg/g) and 276 (29%) had a positive fCal. 28% (77/276) of the patients testing
      positive and 3% (17/686) of those testing negative had an organic diagnosis. At
      50 MUg/g the sensitivity of the test for organic disease was 82%, (95% confidence
      interval [CI] 73-89) and the specificity was 77% (95% CI 74-80), with negative
      predictive value (NPV) and positive predictive value (PPV) of 98% and 28%,
      respectively. A cut-off increase to 150 MUg/g reduces the NPV by 1% whilst
      increasing the PPV to 71%. This would reduce colonoscopy and flexible
      sigmoidoscopy bookings by 10% at the cost of four missed cases of inflammatory
      bowel disease. CONCLUSIONS: This study provides the first evidence on the use of
      fCal testing in primary care. The low prevalence of organic disease in this
      setting has a significant impact on test performance. This suggests a need for
      change in cut-off value, to improve PPV whilst accepting a reduction in test
      sensitivity, if it is to be used as part of the pathway for management of
      patients with suspected IBS.

PMID- 23883069
TI  - Antithyroid medications and psychosis.
AB  - INTRODUCTION: Antithyroid drugs (ATDs) are used in the treatment of
      hyperthyroidism. Very rarely ATDs were reported to trigger acute psychosis in
      patients with no history of psychiatric disturbances. Our aim is to review the
      literature on psychosis as a side effect of ATD and to give a personal opinion on
      this issue. AREAS COVERED: The cases of acute psychosis elicited by ATD are few
      and most were reported many years ago, before radioimmunoassay for thyroid
      stimulating hormone (TSH) and thyroid hormones was introduced. Most of those
      cases lack a description of serum thyroid hormone profile before, during and
      after the appearance of the psychiatric disorder; hence, an abrupt shift from
      hyperthyroidism to euthyroidism or hypothyroidism cannot be excluded. In
      addition, patients underwent specific psychiatric therapy, so that it is
      difficult to attribute the disappearance of the mental disorders to the
      withdrawal of ATD per se. EXPERT OPINION: Patients who develop mental disorders
      while under ATD should be followed by an accurate evaluation of TSH, free
      triiodothyronine (FT3), and free thyroxine (FT4) levels throughout the course of
      the psychiatric disease. The use of new imaging techniques could be helpful in
      ruling out the encephalopathy associated with autoimmune thyroid diseases and
      other cerebral pathologies that might be possible causes of these mental
      disorders.

PMID- 23883070
TI  - Purtscher-like retinopathy associated with dermatomyositis.
AB  - BACKGROUND: To report a rare case of bilateral Purtscher-like retinopathy in a
      Chinese female patient with dermatomyositis. CASE PRESENTATION: An 18-year-old
      woman with lower extremity muscle weakness was admitted due to decreased vision
      of both eyes for two weeks. Ophthalmic examination revealed violaceous eruption
      on eyelids with swelling. Ocular fundus examination revealed multiple cotton wool
      spots and Purtscher flecken, and intra-retinal haemorrhages with pseudo-cherry
      red spot. The erythrocyte sedimentation rate, C-reactive protein, lactate
      dehydrogenase and creatine kinase was measured and found to be increased. A
      diagnosis of Purtscher-like retinopathy associated with dermatomyositis was made
      and the patient was treated with corticosteroids. CONCLUSION: Although
      dermatomyositis is a rare cause of Purtscher-like retinopathy, it is important to
      keep in mind that systemic associations such as dermatomyositis should be ruled
      out in such patients.

PMID- 23883072
TI  - In vitro flowering of orchids.
AB  - Flowering is the most elusive and fascinating of all plant developmental
      processes. The ability to induce flowering in vitro in orchids would reduce the
      relatively long juvenile phase and provide deeper insight into the physiological,
      genetic and molecular aspects of flowering. This review synthesizes all available
      studies that have been conducted on in vitro flowering of orchids with the
      objective of providing valuable clues as to the mechanism(s) that is possibly
      taking place.

PMID- 23883071
TI  - The multifaceted responses of primary human astrocytes and brain microvascular
      endothelial cells to the Lyme disease spirochete, Borrelia burgdorferi.
AB  - The vector-borne pathogen, Borrelia burgdorferi, causes a multi-system disorder
      including neurological complications. These neurological disorders, collectively
      termed neuroborreliosis, can occur in up to 15% of untreated patients. The
      neurological symptoms are probably a result of a glial-driven, host inflammatory
      response to the bacterium. However, the specific contributions of individual
      glial and other support cell types to the pathogenesis of neuroborreliosis are
      relatively unexplored. The goal of this project was to characterize specific
      astrocyte and endothelial cell responses to B. burgdorferi. Primary human
      astrocytes and primary HBMEC (human brain microvascular endothelial cells) were
      incubated with B. burgdorferi over a 72-h period and the transcriptional
      responses to the bacterium were analyzed by real-time PCR arrays. There was a
      robust increase in several surveyed chemokine and related genes, including IL
      (interleukin)-8, for both primary astrocytes and HBMEC. Array results were
      confirmed with individual sets of PCR primers. The production of specific
      chemokines by both astrocytes and HBMEC in response to B. burgdorferi, including
      IL-8, CXCL-1, and CXCL-10, were confirmed by ELISA. These results demonstrate
      that primary astrocytes and HBMEC respond to virulent B. burgdorferi by producing
      a number of chemokines. These data suggest that infiltrating phagocytic cells,
      particularly neutrophils, attracted by chemokines expressed at the BBB (blood
      brain barrier) may be important contributors to the early inflammatory events
      associated with neuroborreliosis.

PMID- 23883073
TI  - Pyruvate production in Candida glabrata: manipulation and optimization of
      physiological function.
AB  - Candida glabrata, a multi-vitamin auxotrophic yeast, can accumulate a large
      amount of pyruvate extracellularly using glucose as the carbon source, a
      characteristic that has facilitated the cost-effective biotechnological
      production of pyruvate on an industrial scale. In this review, we describe the
      current advances in further improving the performance of C. glabrata for
      efficient pyruvate production, which includes: optimization of the vitamin and
      dissolved oxygen concentrations, regulation of intracellular cofactor levels and
      improvement of the environmental robustness of C. glabrata. We also discuss the
      current efforts using systems biology to understand the metabolism of C.
      glabrata. Finally, perspectives on engineering and exploiting C. glabrata as a
      cell factory for efficiently producing various chemicals and materials are
      discussed. 

PMID- 23883074
TI  - Electrically tunable wetting defects characterized by a simple capillary force
      sensor.
AB  - We present a concept of a wetting defect of continuously variable strength based
      on electrowetting, along with a capillary force sensor adapted for the
      characterization of macroscopically heterogeneous surfaces. Patterned electrodes
      submerged under an insulating layer are used to generate potential wells for
      drops of electrically conductive liquids on the solid surface, with a well depth
      that scales with the diameter of the drop and square of the applied alternating
      (AC) voltage. We characterize the strength of the electrowetting trap and the
      hysteretic motion of the drop along the surface, using a simple force sensor
      based on optical imaging of a thin bendable capillary. A force resolution of
      approximately 0.1 MUN is achieved. 

PMID- 23883075
TI  - New bifunctional chelator for 64Cu-immuno-positron emission tomography.
AB  - A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in
      high overall yield from cyclam. An extra functional group (NCS) was introduced to
      the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A
      Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic
      voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH2 complex
      confirmed octahedral geometry, in which copper atom is strongly coordinated by
      four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen
      atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A
      Bn-NCS and then radiolabeled with 64Cu quantitatively at room temperature within
      10 min. Biodistribution studies showed that the 64Cu-labeled TE2A-Bn-NCS
      trastuzumab conjugates maintain high stability in physiological conditions, and
      NIH3T6.7 tumors were clearly visualized up to 3 days by 64Cu-immuno-positron
      emission tomography imaging in animal models.

PMID- 23883076
TI  - A shared haplotype indicates a founder event in Unverricht-Lundborg disease
      patients from Serbia.
AB  - Unverricht-Lundborg disease (ULD) is an autosomal recessive disorder caused by
      dodecamer repeat expansion in the promoter region of the cystatin B (CSTB) gene
      in approximately 90% of the disease alleles worldwide. This study presents
      results of genetic findings in four Serbian unrelated patients with clinical and
      molecular diagnosis of ULD. Using newly established PCR protocol with betaine, we
      detected a homozygous expansion of dodecamer repeats in the CSTB gene in four
      patients with clinical diagnosis of ULD. Our results are in agreement with
      previous studies showing that dodecamer repeats expansion is the most common
      mutation associated with ULD. Haplotype analysis of eight unrelated ULD
      chromosomes was performed using seven markers flanking CSTB gene and one
      intragenic variant. We demonstrated the existence of a founder effect, strongly
      supported by LD calculations. Size of the minimal common haplotype implies that
      the most recent common ancestor of the Serbian ULD patients lived about 110
      generations ago. We showed that Serbian ULD patients share the same common
      ancestor with patients from Baltic countries and North Africa. In the light of
      our data, we proposed extended minimal common haplotype, which could be
      considered as initial haplotype of the founder event common for Serbian, Baltic,
      and North African ULD patients.

PMID- 23883077
TI  - Cytotoxic and potential anticancer constituents from the stems of Schisandra
      pubescens.
AB  - CONTEXT: The diethyl ether extract of the stems of Schisandra pubescens Hemsl. et
      Wils. (Schisandraceae) was found to exhibit cytotoxic activity in vitro. However,
      investigations of the bioactive constituents of this plant have been very
      limited. OBJECTIVE: Elucidation of the cytotoxic constituents of S. pubescens was
      performed. METHODS: Repeated silica gel column chromatography and preparative TLC
      were used for the chemical investigation of the diethyl ether extract of S.
      pubescens stems. All isolates were evaluated for their in vitro cytotoxicity
      against A549, PC-3, KB and KBvin human cancer cell lines. RESULTS: Nine known
      compounds were obtained, including four lignans, epischisandrone (1),
      tigloylgomisin P (2), cagayanone (3) and (-)-gomisin L2 (4), together with five
      triterpenoids, micranoic acid B (5), lancifodilactone H (6), coccinic acid (7),
      schisanlactone B (8) and anwuweizonic acid (9). Compounds 2-6 and 8 showed
      moderate to marginal cytotoxicity, with GI50 values of 11.83-35.65 MUM.
      CONCLUSION: The isolation of 1-9 from S. pubescens and the cytotoxicities of 3-6
      are first reported. Compounds 2-6 and 8 could be the active principles
      responsible for the anticancer effects of S. pubescens.

PMID- 23883079
TI  - Applicability of a different estimation equation of glomerular filtration rate in
      Turkey.
AB  - We aimed to investigate the performance of various creatinine based glomerular
      filtration rate estimation equations that were widely used in clinical practice
      in Turkey and calculate a correction coefficient to obtain a better estimate
      using the isotope dilution mass spectrometry (IDMS)-traceable Modification of the
      Diet in Renal Disease (MDRD) formula. This cross-sectional study included adult
      (>18 years) outpatients and in patients with chronic kidney disease as well as
      healthy volunteers. Iohexol clearance was measured and the precisions and bias of
      the various estimation equations were calculated. A correction coefficient for
      the IDMS-traceable MDRD was also calculated. A total of 229 (113 male/116 female;
      mean age 53.9 +/- 14.4 years) subjects were examined. A median iohexol clearance
      of 39.21 mL/min/1.73 m(2) (range: 6.01-168.47 mL/min/1.73 m(2)) was found. Bias
      and random error for the IDMS-traceable MDRD equation were 11.33 +/- 8.97
      mL/min/1.73 m(2) and 14.21 mL/min/1.73 m(2), respectively. MDRD formula seems to
      provide the best estimates. To obtain the best agreement with iohexol clearance,
      a correction factor of 0.804 must be introduced to IDMS-traceable MDRD equation
      for our study population.

PMID- 23883080
TI  - [Unrealized project of the infectious disease Hospital of Rijeka from 1908 -
      1912].
AB  - Parallel with the design of the main city hospital of Rijeka, architect Francesco
      Mattiassi between 1908 and 1912 made the project for the Infectious disease
      hospital which had to replace existing hospital - subsidiary. After some years of
      disputes regarding the location, decision was reached to place the new hospital
      onto the terrain Sv. Jelena na Plasama (St. Helen at Plase, today Pehlin). The
      infection disease complex was conceived as a pavilion, which was, because of
      better isolation, usual concept for this type of hospitals. Buildings are placed
      to merge with the greenery, connected with road and pedestrian paths. Inside the
      complex there were clean and unclean watch-houses, administration, utility and
      service pavilion, laundry-room, observation pavilion, four patients pavilions and
      necroscopy pavilion with crematorium furnace. Functionality, simplicity and
      temperance are the main characteristics of this, for the time very modern
      architecture with secession style marks. Even today, after more than hundred
      years, this unrealized visionary project, because of its high technical, artistic
      and conceptual level, still effects very contemporary and usable. 

PMID- 23883081
TI  - Dominicans and balneology in the Bohemia and surrounding countries (1650 - 1720).
AB  - The paper tackles the question of balneological treatment available for the
      members of the Order of Preachers in Central Europe between 1650 and 1720. I took
      advantage of a strict record keeping procedure within the Dominican order, which
      required that all members obtain a written permission from the Father Provincial
      before taking any journey beyond local boundaries. As all the records were kept
      in so called "Provincial books" (Libri provinciae) it was possible to identify
      travelling permits issued for balneological treatment and collect data about
      visits to spas from the entire Czech Province. 

PMID- 23883082
TI  - The use of paleo-imaging and microbiological testing in the analysis of antique
      cultural material: multislice tomography, and microbial analysis of the Trogir
      Cathedral cope hood depicting St. Martin and a beggar.
AB  - Paleoradiology is the study of biological and other materials from archeological
      settings through the use of various medical imaging techniques. Although it is
      most often used in the scientific study of ancient human remains, it can also be
      used to study metals, ceramics, paper, and clothes. The aim of this study was to
      test two paleoimaging techniques (MSCT and mammography) in the analysis of an
      important Croatian liturgical vestment: the hood of a bishop's cope from St.
      Lawrence's Treasury in Trogir depicting St. Martin and a beggar. To ensure a safe
      environment for scientists participating in the analysis, a preliminary
      microbiological analysis was performed, which contributed to the database of
      microbiological flora found on Croatian archeological remains and relics studied
      to date. Due to a great amount of metal filaments, the paleoradiological analysis
      did not produce satisfactory results. However, a digitally enhanced image clearly
      showed fine metal embroidery of the hood that was not so easily perceived by
      naked eye. This article argues in favor of expanding paleoradiological studies on
      materials other than human remains and also of publishing unsatisfactory results,
      as important lessons for future development of techniques and methods to analyze
      ancient remains and seek answers about human historical and cultural heritage. 

PMID- 23883083
TI  - Earthquakes and plague during Byzantine times: can lessons from the past improve
      epidemic preparedness.
AB  - Natural disasters have always been followed by a fear of infectious diseases.
      This raised historical debate about one of the most feared scenarios: the
      outbreak of bubonic plague caused by Yersinia pestis. One such event was recorded
      in the Indian state Maharashtra in 1994 after an earthquake. In multidisciplinary
      historical approach to the evolution of plague, many experts ignore the
      possibility of natural foci and their activation. This article presents
      historical records from the Byzantine Empire about outbreaks of the Plague of
      Justinian occurring months or even up to a year after high-magnitude earthquakes.
      Historical records of plague outbreaks can be used to document existence of
      natural foci all over the world. Knowledge of these historical records and the
      contemporary examples of plague support the assumption that, in terms of
      organising humanitarian aid, poor monitoring of natural foci could lead to
      unpredictable epidemiological consequences after high-magnitude earthquakes. 

PMID- 23883084
TI  - [The Code of Medieval Sibenik and care for health culture issues].
AB  - The Code of Sibenik dates back to the 13th century and is impressive inasmuch as
      it pays a lot of attention to health culture issues. It brings a number of
      hygienic and sanitary measures such as the ban to keep pigs in the town, to throw
      "filth and decay" on public roads, to unload and sell fish in places not intended
      for selling, to display and sell meat outside butcheries, to skin animals outside
      butcheries, to sell carrion meat, and the order to bakers to bake bread
      thoroughly. It pays particular attention to public bodies of water such as ponds
      and to watersupply, and the town subsidised half the welling costs. In respect to
      general health protection, the Code banned corpse kissing to prevent infections,
      and graves were removed from the town centre for the same reason (because they
      "stank"). The "insane" and "simple minded" could not close legal deals. The fact
      that the town employed a trained physician - medicus - (in addition to a barber)
      suggests that it was the physician's job to decide who of the townspeople
      belonged to the category of the mentally challenged. 

PMID- 23883085
TI  - Post-mortem Cesarean section and embryotomy: myth, medicine, and gender in Greco
      Roman culture.
AB  - This article focuses on cesarean section carried out after the mother's death to
      rescue the living infant and on embryotomy, a medical procedure to save the
      mother described as early as the Hippocratic writings (5th to 4th century B.C.)
      and practiced until the times of Paul of Aegina (7th century A.D). The available
      sources do not mention cesarean section on a living mother to save the infant. On
      the other side, writings on embryotomy state clearly that Greek and Roman
      physicians strove hard to save women's lives. Written in ancient, male-centered
      societies, these texts convey an unequivocal positive attitude towards women,
      despite current misogynist assessments by philosophers and physicians who
      considered women inferior, based on their organic and biological features. 

PMID- 23883086
TI  - Collyria seals in the Roman Empire.
AB  - Roman seals associated with collyria (Latin expression for eye drops/washes and
      lotions for eye maintenance) provide valuable information about eye care in the
      antiquity. These small, usually stone-made pieces bore engravings with the names
      of eye doctors and also the collyria used to treat an eye disease. The collyria
      seals have been found all over the Roman empire and Celtic territories in
      particular and were usually associated with military camps. In Hispania (Iberian
      Peninsula), only three collyria seals have been found. These findings speak about
      eye care in this ancient Roman province as well as about of the life of the time.
      This article takes a look at the utility and social significance of the collyria
      seals and seeks to give an insight in the ophthalmological practice of in the
      Roman Empire. 

PMID- 23883087
TI  - Medicinal aspects of opium as described in Avicenna's Canon of Medicine.
AB  - Throughout history, opium has been used as a base for the opioid class of drugs
      used to suppress the central nervous system. Opium is a substance extracted from
      the opium poppy (Papaver somniferum L.). Its consumption and medicinal
      application date back to antiquity. In the medieval period, Avicenna, a famous
      Persian scholar (980-1037 AD) described poppy under the entry Afion of his
      medical encyclopedia Canon of Medicine. Various effects of opium consumption,
      both wanted and unwanted are discussed in the encyclopedia. The text mentions the
      effects of opioids such as analgesic, hypnotic, antitussive, gastrointestinal,
      cognitive, respiratory depression, neuromuscular disturbance, and sexual
      dysfunction. It also refers to its potential as a poison. Avicenna describes
      several methods of delivery and recommendations for doses of the drug. Most of
      opioid effects described by Avicenna have subsequently been confirmed by modern
      research, and other references to opium use in medieval texts call for further
      investigation. This article highlights an important aspect of the medieval
      history of medicine. 

PMID- 23883088
TI  - [Sketches from ecclesiastic history of Rijeka illustrating the relationship
      between Christianity and health care].
AB  - The first part of the article looks into the contribution of Christianity to
      health care in the Middle Ages. In those times, monasteries used to take care of
      the sick, pilgrims, and travellers. The second part brings interesting
      information about health care institutions from the church history of Rijeka.
      Local circumstances favoured setting up an infirmary in St Sebastian's street.
      Adjacent to the Church of the Assumption was the asylum of the Holy Spirit; the
      name had remained with the town hospital of Rijeka until 1945. Four fraternities
      played a major role in local health care: St Mary's, St Michael's, St Vitus', and
      St John's. Their members helped each other and took care of the weak and the
      sick. The lazarets of Rijeka, one in Mandrac and the other in Martinscica, had
      their own chapels and organised pastoral care. The first bishop of Rijeka,
      Isidoro Sain, established the Vicariate of St Joseph in the town hospital on 1
      January 1928. Health care in Rijeka had strong ties with the Sisters of Mercy,
      who arrived in the town in 1858 and have been working in a variety of healthcare
      institutions to this day.

PMID- 23883089
TI  - Beginning of modern meteorological measurements in Fiume (Rijeka).
AB  - When reporting on extreme weather conditions in the city of Rijeka (former
      Fiume), it is often specified " ... since the beginning of measurements in 1948".
      In reality the modern meteorological measurements in Fiume had started already in
      1868, when the Austrian Imperial Academy of Science established the
      meteorological station. The station was operating at the Naval Academy, under the
      supervision of prof. dr. Emil Stahlberger, the first university professor of
      physics in Fiume (Rijeka). The following year the station was equipped with
      mareograph (marigraph/tide gauge). Based on three years measurements, prof.
      Stahlberger published the first book on tides in the Rijeka bay (Ueber die Ebbe
      und Flut in der Rhede von Fiume). After his sudden death, Prof. Peter Salcher,
      his succesor at the Physics chair at the Naval academy, took charge of the
      Meteorological station. In 1884. He published the book entitled Climate in Rijeka
      and Opatija (Das Klima von Fiume und Abbazia). The meteorological data in the
      book are presented in the very same way as it is done today, and therefore these
      data can be used for comparative purposes regarding climate variations/ changes. 

PMID- 23883090
TI  - [Panfilo Castaldi (1430? - 1487): a physician-typographer].
AB  - The issue about whether it was Johann Gutenberg in Mainz or Panfilo Castaldi in
      Feltre (in the Italian region of Veneto) to first invent movable metal type for
      printing around 1450 still raises a controversy, even though Gutenberg is
      generally perceived as the one. What is beyond doubt, however, is that Castaldi
      pioneered the new revolutionary printing method with the historical texts written
      by great physicians such as Hippocrates, Galen, and Avicenna. His early
      publishing success raised bitter competition all around him, which eventually
      drove him out of this flourishing business, and he returned to his long-neglected
      medical profession. Castaldi's new "art" was received coldly by his apprehensive
      fellow citizens. As soon as he was buried, they invaded the printing office and,
      believing that the printing machines were the "devil's instruments", tore it
      apart. 

PMID- 23883091
TI  - Wolfgang Amadeus Mozart: the death of a genius.
AB  - The early and unexpected death of Wolfgang Amadeus Mozart (Salzburg, 1756 -
      Vienna, 1791) was a mystery from the very first day and the subject of wildest
      speculations and adventurous assertions. Over the last 100 years, medical science
      has investigated the physical sufferings and the mysterious death of Mozart with
      increasing intensity. The aim of this article was to recreate Mozart's
      pathography relying on the his correspondence with father Leopold and sister
      Nannerl and on reports from his physicians and contemporaries. The rumour that
      Mozart was poisoned followed shortly after his death on 5 December 1791, at the
      age of 35, and has survived to this day. The alleged culprits were his physician
      van Swieten, Mozart's freemasons lodge, and the Imperial Chapel Master Salieri.
      Mozart however died of chronic kidney disease and ultimately of uraemia. If
      kidney damage reaches a critical point, even a minimum additional stress can lead
      to its failure. This usually occurs in the fourth decade of life. Next time we
      listen to Mozart, we should remember that this apparently happy person was
      actually a precocious boy, ripped of his childhood, whose short life was an
      endless chain of complaints, fatigue, misery, concern, and malady. 

PMID- 23883092
TI  - [In memoriam: 100th anniversary of Professor Dragutin (Drago) Vrabnic birthday].
AB  - Professor Dragutin (Drago) Vrbanic, MD, PhD (1912 - 1996) was an eminent figure
      of Croatian medicine, especially in Rijeka and Istria. His work includes a number
      of publications and managerial accomplishments that encouraged the development of
      gynaecology and obstetrics. He can also be credited for the organisation and
      affirmation of midwifery in Rijeka. Professor Vrbanic was highly appreciated not
      only for his educational and scientific achievements, but also as a valuable
      mentor to younger colleagues, whom he encouraged to pursue their profession to
      the fullest. 

PMID- 23883093
TI  - [Professor Drago Vrbanic - the important contribution to the development of
      oncology in Rijeka].
AB  - In Rijeka of the 1950s professor Drago Vrbanic was well-known as an excellent
      gynaecologist and surgeon, especially in the field of gynaecological malignant
      tumours. He headed the gynaecological and radiology departments of the Sobol
      Brothers General Hospital, and successfully applied several radiotherapy methods.
      Later in the 1960s, he introduced modern classification of tumours and
      multidisciplinary expertise in the diagnostics and treatment of gynaecological
      cancers. He combined a variety of operation procedures and methods with modern
      radiotherapy, significantly improving the results of malignant tumour therapy. 

PMID- 23883095
TI  - Safety profile of two novel antiepileptic agents approved for the treatment of
      refractory partial seizures: ezogabine (retigabine) and perampanel.
AB  - INTRODUCTION: Complex-partial seizures are frequently resistant to antiepileptic
      therapy. Two new medications with mechanisms of action novel within the
      antiepileptic class have recently received approval for the adjunctive treatment
      of partial (focal) seizures. AREAS COVERED: A Medline search was conducted to
      identify preclinical and clinical studies of ezogabine and perampanel. This was
      supplemented with additional articles obtained from online sources and
      information provided by the FDA and the manufacturers. The focus of this review
      is on the safety profiles of ezogabine (retigabine), a novel antiepileptic that
      targets voltage-gated potassium channels, and perampanel, a noncompetitive alpha
      amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamate receptor antagonist.
      EXPERT OPINION: Central nervous system effects are predominant within the adverse
      event profiles of both ezogabine and perampanel. In addition, ezogabine exerts
      its inhibitory effects on potassium channels in the urogenital tract potentially
      resulting in urinary retention and related outcomes. Recent reports of blue
      discoloration of the skin and in the retinas of long-term ezogabine users have
      surfaced. Both drugs have demonstrated the ability to induce neuropsychiatric
      symptoms. Though both are welcome additions to the antiepileptic drug class,
      additional monitoring, appropriate counseling, and careful selection of patients
      are warranted to minimize adverse events.

PMID- 23883094
TI  - Androgen response element of the glycine N-methyltransferase gene is located in
      the coding region of its first exon.
AB  - Androgen plays an important role in the pathogenesis of PCa (prostate cancer).
      Previously, we identified GNMT (glycine N-methyltransferase) as a tumour
      susceptibility gene and characterized its promoter region. Besides, its enzymatic
      product-sarcosine has been recognized as a marker for prognosis of PCa. The goals
      of this study were to determine whether GNMT is regulated by androgen and to map
      its AREs (androgen response elements). Real-time PCR analyses showed that R1881,
      a synthetic AR (androgen receptor) agonist induced GNMT expression in AR-positive
      LNCaP cells, but not in AR-negative DU145 cells. In silico prediction showed that
      there are four putative AREs in GNMT-ARE1, ARE2 and ARE3 are located in the
      intron 1 and ARE4 is in the intron 2. Consensus ARE motif deduced from published
      AREs was used to identify the fifth ARE-ARE5 in the coding region of exon 1.
      Luciferase reporter assay found that only ARE5 mediated the transcriptional
      activation of R1881. ARE3 overlaps with a YY1 [Yin and Yang 1 (motif (CaCCATGTT,
      +1118/+1126)] that was further confirmed by antibody supershift and ChIP
      (chromatin immunoprecipitation) assays. EMSA (electrophoretic mobility shift
      assay) and ChIP assay confirmed that AR interacts with ARE5 in vitro and in vivo.
      In summary, GNMT is an AR-targeted gene with its functional ARE located at
      +19/+33 of the first exon. These results are valuable for the study of the
      influence of androgen on the gene expression of GNMT especially in the
      pathogenesis of cancer. 

PMID- 23883096
TI  - Rational design of a transition state analogue with picomolar affinity for
      Pseudomonas aeruginosa PvdQ, a siderophore biosynthetic enzyme.
AB  - The Pseudomonas aeruginosa enzyme PvdQ can process different substrates involved
      in quorum-sensing or in siderophore biosynthesis. Substrate selectivity was
      evaluated using steady-state kinetic constants for hydrolysis of N-acyl
      homoserine lactones (HSLs) and p-nitrophenyl fatty acid esters. PvdQ prefers
      substrates with alkyl chains between 12 and 14 carbons long that do not bear a 3
      oxo substitution and is revealed here to have a relatively high specificity
      constant for selected N-acyl-HSLs (kcat/KM = 10(5) to 10(6) M(-1) s(-1)).
      However, endogenous P. aeruginosa N-acyl-HSLs are >=100-fold disfavored,
      supporting the conclusion that PvdQ was not primarily evolved to regulate
      endogenous quorum-sensing. PvdQ plays an essential biosynthetic role for the
      siderophore pyoverdine, on which P. aeruginosa depends for growth in iron-limited
      environments. A series of alkylboronate inhibitors was found to be reversible,
      competitive, and extremely potent (Ki >= 190 pM). A 1.8 A X-ray structure shows
      that 1-tridecylboronic acid forms a monocovalent bond with the N-terminal beta
      chain Ser residue in the PvdQ heterodimer, mimicking a reaction transition state.
      This boronic acid inhibits growth of P. aeruginosa in iron-limited media,
      reproducing the phenotype of a genetic pvdQ disruption, although co
      administration of an efflux pump inhibitor is required to maintain growth
      inhibition. These findings support the strategy of designing boron-based
      inhibitors of siderophore biosynthetic enzymes to control P. aeruginosa
      infections. 

PMID- 23883097
TI  - Pulmonary delivery of nanosized alendronate for decorporation of inhaled heavy
      metals: formulation development, characterization and gamma scintigraphic
      evaluation.
AB  - CONTEXT: Medical management of heavy metal toxicity including radioactive ones is
      the cause of concern because of their increased use in energy production,
      healthcare and mining. As inhalation is one of the primary routes for
      internalization, a formulation is needed to trap metal(s) at the portal of entry
      itself. OBJECTIVE: Objective was to formulate and characterize a nanonized dry
      powder inhaler (DPI) formulation of alendronate sodium as potential inhalable
      antidote for chelating metal toxicants. METHODS: In vitro binding studies of
      alendronate with respect to seven non-radioactive heavy metals were carried out
      using UV-spectroscopy and HPLC. Nanonizing of alendronate particles was achieved
      by antisolvent precipitation using Pluronic-F68 as stabilizer. Characterization
      was done with the help of SEM, TEM FT-IR, XRD, DSC, NMR spectroscopy and PSD
      studies. In vitro and in vivo pulmonary deposition studies were carried out using
      gamma scintigraphy, followed by a limited pharmacokinetic study in humans.
      RESULTS: In vitro binding studies confirmed the chelating action of alendronate.
      Anderson cascade impaction showed that nano-alendronate exhibited significantly
      higher respirable fraction (58.25 +/- 1.32%) compared to the micronized form
      (28.7 +/- 0.59%). Scintigraphy results showed significant increase in the
      alveolar deposition of drug post-nanonizing. CONCLUSION: Results strongly
      indicate the role of nano-alendronate DPI as potential inhalable antidote for
      neutralizing heavy metal toxicity, including radio-metal contamination.

PMID- 23883098
TI  - Self-catalyzed immobilization of GST-fusion proteins for genome-encoded biochips.
AB  - With the surge of proteomic information that has become available in recent years
      from genome sequencing projects, selective and robust technologies for making
      protein biochips have become increasingly desirable. Herein, we describe the
      development of small-molecule SNAr electrophiles (smSNAREs), a new class of
      capture probes that enables a selective, single-step immobilization for protein
      biochips. This enzymology-driven approach rides on the binding and catalytic
      mechanism of SjGST. We have designed and synthesized mechanism-based substrate
      analogs 3, 4, and 5 as electrophilic precursors for conjugation of glutathione S
      transferase (GST) or any of its fusion proteins. Upon evaluating the conjugation
      of these probes to glutathione in the presence of SjGST via UV-visible
      spectroscopy (UV-vis) and LC-MS techniques, we found that 3, 4, and 5 were
      transferable to GSH. Through the anchoring of alkyne 5 as a smSNARE probe on
      glass surface, we demonstrate the single-step, self-catalyzed immobilization of
      SjGST. Fluorescence imaging quantitatively revealed an 18-fold increase in
      selective binding of SjGST over random orientations (due to nonspecific binding)
      of the protein. Binding between GST and smSNARE surface is robust and does not
      reverse upon adding up to 100 mM GSH. Further, a 6-fold increase in resolution
      for the smSNARE surface probe was observed over commonly employed commercially
      available GSH-epoxy surfaces. Detailed control experiments revealed insights into
      the reversibility of binding and catalysis of GSH to form conjugation products
      with 5 in the presence of the enzyme. As an application of this protein capture
      technology, we printed alkaloid biosynthesis enzyme, isonitrile synthase (IsnA),
      to result in a biochip. Because proteins bearing a GST-fusion purification tag
      are commonly created through the pGEX expression system, these findings show
      broad potential applicability to genome-wide studies and proteomic platforms.

PMID- 23883099
TI  - Does substance abuse contribute to further risk of falls in dementia.
AB  - This study aimed to predict the risk of falls by focusing on substance abuse in
      the elderly with dementia. Our national cross-sectional survey included 1210
      elderly Malaysian demented subjects. The study identified the effects of age,
      ethnicity, sex differences, marital status, educational level, and substance
      abuse on the likelihood of falls in the elderly with dementia. The multivariate
      logistic regression model was used to analyze data collected from samples. The
      prevalence of falls was about 17% among subjects and significantly increased with
      age (p = .006). Furthermore, the results showed that age (OR = 1.03), ethnicity
      (OR = 1.69), substance abuse (OR = 1.68), and female sex (OR = 1.45)
      significantly enhanced the risk of falls in respondents (p < .05). Educational
      level and marital status had no significant effects on the likelihood of falls (p
      > .05). However, the findings provided evidence of an additional effect of
      substance abuse on further risk of falls in older adults with dementia.

PMID- 23883100
TI  - Synthesis and spectroscopic and spectroelectrochemical characterization of a new
      family of 44e(-) tris-phosphido-bridged palladium triangles.
AB  - Triangular clusters containing a [M3(MU-PR2)3](+) core are very common in
      platinum chemistry but were virtually unknown for M = Pd. Herein we describe the
      synthesis and characterization of several palladium derivatives belonging to this
      class. The trinuclear monohalide clusters {Pd3}(CO)2X [{Pd3} = Pd3(MU-PBu(t)2)3;
      X = Br, I] were prepared by reacting [(n)Bu4N]X or KX with the dinuclear complex
      [Pd(PBu(t)2H)(MU-PBu(t)2)]2 and H2O under an atmosphere of CO. The reaction of
      {Pd3}(CO)2I with CNBu(t) leads to the substitution of all the terminal ligands to
      afford the symmetrical cluster [{Pd3}(CNBu(t))3]I. The latter reacts with TlPF6
      (excess) or AgCF3SO3 (1:1 ratio) to give anion metathesis, whereas the addition
      of a second equivalent of Ag(+) causes cluster oxidation to the thermally stable
      paramagnetic 43e(-) dication [{Pd3}(CNBu(t))3](2+). The cationic clusters
      [{Pd3}(CO)2(L)]PF6 (L = NCCH3, Py or CO) were obtained by reacting {Pd3}(CO)2I
      with TlPF6, under nitrogen in acetonitrile or in pyridine or under 1 atm of
      carbon monoxide in THF. Finally, {Pd3}(CO)2Cl was achieved by the reaction of
      [{Pd3}(CO)3]PF6 with [(PPh3)2N]Cl. All clusters have been obtained in good yields
      and purity and have been characterized by microanalysis and IR and multinuclear
      NMR spectroscopy. Single crystal X-ray diffraction studies on {Pd3}(CO)2Br and
      [{Pd3}(CNBu(t))3]CF3SO3 are also reported. The cyclovoltammetric profile
      exhibited by the palladium clusters prepared in this work is characterized by the
      presence of two monoelectronic oxidation processes whose reversibility and
      potentials depend on the nature of the ligands. Moreover, the UV-vis and IR
      spectroelectrochemical analysis of {Pd3}(CO)2I, [{Pd3}(CO)3]PF6 and
      [{Pd3}(CNBu(t))3]PF6 allowed the spectroscopical characterization of some
      electrogenerated oxidized species and provided some detail for the redox-coupled
      reactions of metastable products. 

PMID- 23883101
TI  - Insensitivity of tryptophan fluorescence to local charge mutations.
AB  - The steady state fluorescence spectral maximum (lambdamax) for tryptophan 140 of
      Staphylococcal nuclease remains virtually unchanged when nearby charged groups
      are removed by mutation, even though large electrostatic effects on lambdamax
      might be expected. To help understand the underlying mechanism of this curious
      result, we have modeled lambdamax with three sets of 50-ns molecular dynamics
      simulations in explicit water, equilibrated with excited state and with ground
      state charges. Semiempirical quantum mechanics and independent electrostatic
      analysis for the wild-type protein and four charge-altering mutants were
      performed on the chromophore using the coordinates from the simulations.
      Electrostatic contributions from the nearby charged lysines by themselves
      contribute 30-90 nm red shifts relative to the gas phase, but in each case,
      contributions from water create compensating blue shifts that bring the predicted
      lambdamax within 2 nm of the experimental value, 332 +/- 0.5 nm for all five
      proteins. Although long-range collective interactions from ordered water make
      large blue shifts, crucial for determining the steady state lambdamax for
      absorption and fluorescence, such blue shifts do not contribute to the amplitude
      of the time dependent Stokes shift following excitation, which comes from nearby
      charges and only ~6 waters tightly networked with those charges. We therefore
      conclude that for STNase, water and protein effects on the Stokes shift are not
      separable. 

PMID- 23883102
TI  - Occurrence and transport of perfluoroalkyl acids (PFAAs), including short-chain
      PFAAs in Tangxun Lake, China.
AB  - Short-chain perfluoroalkyl acids (PFAAs), which have less than seven fluorinated
      carbons, have been introduced as substitutes for eight-carbon homologue products.
      In this study, water, sediment, and biological samples (fish and plant) were
      collected from Tangxun Lake, which is located near a production base of the
      fluorochemical industry in Wuhan, China. Perfluorobutane sulfonate (PFBS) and
      perfluorobutanoic acid (PFBA) were the predominant PFAAs in surface water, with
      average concentrations of 3660 ng/L and 4770 ng/L, respectively. However,
      perfluorooctane sulfonate (PFOS) was the most abundant PFAA in sediments, with an
      average concentration of 74.4 ng/g dw. The organic carbon normalized distribution
      coefficients (KOC) indicated that short-chain PFAAs (CF2 < 7) tended to have
      lower adsorption potentials than PFOS, perfluorooctanoic acid (PFOA), and longer
      perfluoroalkyl chain compounds. PFBS and PFBA could transport to a farther
      distance in the horizontal direction along the water flow and infiltrate into
      deeper depths in the vertical direction. However, levels of PFOS and PFOA in
      water dropped exponentially along the current, and their proportions were
      decreased gradually with the increasing depth in sediment cores. Furthermore,
      values of log bioconcentration factor (BCF) of the short-chain PFAAs were all
      relatively low (<1), indicating no bioaccumulation potentials for short-chain
      PFAAs in aquatic species. 

PMID- 23883103
TI  - Water oxidation catalysis: electrocatalytic response to metal stoichiometry in
      amorphous metal oxide films containing iron, cobalt, and nickel.
AB  - Photochemical metal-organic deposition (PMOD) was used to prepare amorphous metal
      oxide films containing specific concentrations of iron, cobalt, and nickel to
      study how metal composition affects heterogeneous electrocatalytic water
      oxidation. Characterization of the films by energy-dispersive X-ray spectroscopy
      and X-ray photoelectron spectroscopy confirmed excellent stoichiometric control
      of each of the 21 complex metal oxide films investigated. In studying the
      electrochemical oxidation of water catalyzed by the respective films, it was
      found that small concentrations of iron produced a significant improvement in
      Tafel slopes and that cobalt or nickel were critical in lowering the voltage at
      which catalysis commences. The best catalytic parameters of the series were
      obtained for the film of composition a-Fe20Ni80. An extrapolation of the
      electrochemical and XPS data indicates the optimal behavior of this binary film
      to be a manifestation of iron stabilizing nickel in a higher oxidation level.
      This work represents the first mechanistic study of amorphous phases of binary
      and ternary metal oxides for use as water oxidation catalysts, and provides the
      foundation for the broad exploration of other mixed-metal oxide combinations. 

PMID- 23883104
TI  - Gastro oesophageal reflux disease (GORD)-related symptoms and its association
      with mood and anxiety disorders and psychological symptomology: a population
      based study in women.
AB  - BACKGROUND: Psychopathology seems to play a role in reflux pathogenesis and vice
      versa, yet few population-based studies have systematically investigated the
      association between gastro-oesophageal reflux disease (GORD) and psychopathology.
      We thus aimed to investigate the relationship between GORD-related symptoms and
      psychological symptomatology, as well as clinically diagnosed mood and anxiety
      disorders in a randomly selected, population-based sample of adult women.
      METHODS: This study examined data collected from 1084 women aged 20-93 yr
      participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were
      identified using the Structured Clinical Interview for DSM-IV-TR Research
      Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was
      assessed using the General Health Questionnaire (GHQ-12). GORD-related symptoms
      were self-reported and confirmed by medication use where possible and lifestyle
      factors were documented. RESULTS: Current psychological symptomatology and mood
      disorder were associated with increased odds of concurrent GORD-related symptoms
      (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively).
      Current anxiety disorder also tended to be associated with increased odds of
      current GORD-related symptoms (p = 0.1). Lifetime mood disorder was associated
      with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR
      1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold
      increased odds of lifetime GORD-related symptoms in obese but not non-obese
      participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0). CONCLUSIONS: These
      results indicate that psychological symptomatology, mood and anxiety disorders
      are positively associated with GORD-related symptoms. Acknowledging this common
      comorbidity may facilitate recognition and treatment, and opens new questions as
      to the pathways and mechanisms of the association.

PMID- 23883105
TI  - Premature senescence and cellular phenotype transformation of mesangial cells
      induced by TGF-B1.
AB  - BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is a polypeptide member
      of the transforming growth factor beta superfamily of cytokines and performs many
      cellular functions. Its overexpression may lead to renal fibrosis. AIM: This
      study planed to investigate the effects of TGF-beta1 on the cell cycle and
      phenotype of mesangial cells. METHODS: Rat mesangial cells were cultured together
      with different concentrations (0, 1, 2, 5, and 10 ng/mL) of TGF-beta1 for
      specified times from 0 min to 72 h. 0 ng/mL TGF-beta1 and 0 min served as
      controls. Cell cycles were assessed by flow cytometry and alpha-smooth muscle
      actin expression (alpha-SMA) protein expression by western blot analysis. All
      data were presented as Mean +/- SD. Statistical analysis was performed by using
      one-way analysis of variance and correlation analysis. Results were considered
      significant at p < 0.05. RESULTS: After 15 min of co-culture with different
      concentrations of TGF-beta1, the percentage of mesangial cells in G0/G1 phase was
      significantly elevated compared to the control (p < 0.05). 12 h co-culture
      induced cell hyperplasia, 24 h co-culture obvious up-regulation of alpha-SMA (p <
      0.01) and one or two cells' myofibroblast phenotype transition, and 36 h co
      culture several cells' phenotype transition. Correlation analysis prompted that
      the TGF-beta1-induced premature aging was time-dependent (p < 0.01). CONCLUSION:
      TGF-beta1 may induce mesangial cells' premature senescence and myofibroblast-like
      phenotype transformation time-dependently, which may contribute to the
      development of early stage of glomerulosclerosis.

PMID- 23883106
TI  - Electrical property of acupoints.

PMID- 23883107
TI  - Individual differences in solving arithmetic word problems.
AB  - BACKGROUND: With the present functional magnetic resonance imaging (fMRI) study
      at 3 T, we investigated the neural correlates of visualization and verbalization
      during arithmetic word problem solving. In the domain of arithmetic,
      visualization might mean to visualize numbers and (intermediate) results while
      calculating, and verbalization might mean that numbers and (intermediate) results
      are verbally repeated during calculation. If the brain areas involved in number
      processing are domain-specific as assumed, that is, that the left angular gyrus
      (AG) shows an affinity to the verbal domain, and that the left and right
      intraparietal sulcus (IPS) shows an affinity to the visual domain, the activation
      of these areas should show a dependency on an individual's cognitive style.
      METHODS: 36 healthy young adults participated in the fMRI study. The participants
      habitual use of visualization and verbalization during solving arithmetic word
      problems was assessed with a short self-report assessment. During the fMRI
      measurement, arithmetic word problems that had to be solved by the participants
      were presented in an event-related design. RESULTS: We found that visualizers
      showed greater brain activation in brain areas involved in visual processing, and
      that verbalizers showed greater brain activation within the left angular gyrus.
      CONCLUSIONS: Our results indicate that cognitive styles or preferences play an
      important role in understanding brain activation. Our results confirm, that
      strong visualizers use mental imagery more strongly than weak visualizers during
      calculation. Moreover, our results suggest that the left AG shows a specific
      affinity to the verbal domain and subserves number processing in a modality
      specific way.

PMID- 23883108
TI  - Migraine prevalence in patients with atrial septal defect.
AB  - BACKGROUND: Patients with a patent foramen ovale have a high prevalence of
      migraine with aura (MA). However, whether patients with an atrial septal defect
      (ASD) have a high prevalence of migraine remains unclear. The present study aimed
      to determine the prevalence of migraine and its clinical characteristics in
      patients with ASD. FINDINGS: Ninety-five patients (age >= 20 years) who had
      undergone percutaneous ASD closure responded to a questionnaire used by
      neurologists to diagnose migraine either with or without aura. We diagnosed
      migraine before ASD closure according to the criteria of the International
      Headache Society. The overall prevalence of migraine seemed to be higher in the
      present study than in the Japanese general population (24.2% vs. 9.4%,
      respectively). All patients with MA were female and significantly younger than
      those without migraine (p < 0.01). CONCLUSIONS: Our findings suggested that the
      susceptibility to the development of MA differs according to sex and age in
      patients with cardiac shunt.

PMID- 23883109
TI  - Outcomes following renal transplantation in older people: a retrospective cohort
      study.
AB  - BACKGROUND: The mean age of renal transplant recipients is rising, with age no
      longer considered a contraindication. Outcomes in older patients have not,
      however, been fully defined. The aim of our study is to evaluate outcomes in
      older people following renal transplantation at a Scottish regional transplant
      unit. METHODS: All renal transplants from January 2001 to December 2010 were
      analysed (n = 762). Outcomes following renal transplantation in people over 65
      years old were compared to those in younger patients. Outcome measures were:
      delayed graft function (DGF), primary non-function (PNF), biopsy proven acute
      rejection (BPAR), serum creatinine at 1 year and graft and recipient survival.
      Lengths of initial hospital stay and re-admission rates were also assessed.
      Student's T-Test was used to analyse continuous variables, Pearson's Chi-Squared
      test for categorical variables and the Kaplan-Meier estimator for survival
      analysis. RESULTS: Older recipients received proportionately more kidneys from
      older donors (27.1% vs. 6.3%; p < 0.001). Such kidneys were more likely to have
      DGF (40.7% vs. 16.9%; p < 0.001). Graft loss at 1 year was higher in kidneys from
      older donors (15.3% vs. 7.6%; p = 0.04). There was no significant difference in
      patient survival at 1 year based on the age of the donor kidney. Recipient age
      did not affect DGF (16.9% vs. 18.5%; p = 0.77) or graft loss at 1 year (11.9% vs.
      7.8%; p = 0.28). Older recipients were, however, more likely to die in the first
      year post transplant (6.8% vs. 2.1%; p = 0.03). BPAR was less common in older
      patients (6.8% vs. 22%; p < 0.01). Older recipients were more likely to be
      readmitted to hospital (31.8% vs. 10.9%; p < 0.001). CONCLUSIONS: Older patients
      experience good outcomes following renal transplantation and donor or recipient
      age alone should not preclude this treatment. An awareness of this in clinicians
      managing older patients is important since the prevalence of End Stage Renal
      Disease is increasing in this age group.

PMID- 23883110
TI  - Color variation assay of the anthocyanins from Acai Fruit (Euterpe oleracea): a
      potential new dye for vitreoretinal surgery.
AB  - AIM: The goals of this study were to determine the potential for use of the
      natural anthocyanins from the acai fruit (Euterpe oleracea) during vitreoretinal
      surgery and the ideal physicochemical properties of the dye. METHODS: We
      evaluated the color variations of the dye at different pHs and osmolarities with
      or without the use of mordants as a potential new tool for internal limiting
      membrane peeling. The extracts of anthocyanin from the acai fruit were analyzed
      by spectrophotometry to determine the degree of color variations associated with
      various pHs and osmolarities. The experiments were conducted in test tubes filled
      with tryptophan soya media and Petri dishes prepared with agar media. RESULTS: We
      observed various shades of green, red, and purple in the extracts of the
      anthocyanin dye at different pHs and osmolarities. The assay to adjust the
      anthocyanin solution similar to the physiologic retinal environment (osmolarity,
      300 mOsm; pH, 7.00) resulted in a shade of purple that may be useful to stain the
      intraocular microstructures during vitreoretinal surgery. The physicochemical
      property of the purple anthocyanin solutions from the acai fruit was observed at
      physiologic pH and osmolarity. CONCLUSION: Anthocyanins from the acai fruit may
      be useful to enhance visualization of the intraocular microstructures during
      vitreoretinal surgery.

PMID- 23883111
TI  - Mitochondrial polymorphisms impact outcomes after severe traumatic brain injury.
AB  - Patient outcomes are variable following severe traumatic brain injury (TBI);
      however, the biological underpinnings explaining this variability are unclear.
      Mitochondrial dysfunction after TBI is well documented, particularly in animal
      studies. The aim of this study was to investigate the role of mitochondrial
      polymorphisms on mitochondrial function and patient outcomes out to 1 year after
      a severe TBI in a human adult population. The Human MitoChip V2.0 was used to
      evaluate mitochondrial variants in an initial set of n=136 subjects. SNPs found
      to be significantly associated with patient outcomes [Glasgow Outcome Scale
      (GOS), Neurobehavioral Rating Scale (NRS), Disability Rating Scale (DRS), in
      hospital mortality, and hospital length of stay] or neurochemical level
      (lactate:pyruvate ratio from cerebrospinal fluid) were further evaluated in an
      expanded sample of n=336 subjects. A10398G was associated with DRS at 6 and 12
      months (p=0.02) and a significant time by SNP interaction for DRS was found
      (p=0.0013). The A10398 allele was associated with greater disability over time.
      There was a T195C by sex interaction for GOS (p=0.03) with the T195 allele
      associated with poorer outcomes in females. This is consistent with our findings
      that the T195 allele was associated with mitochondrial dysfunction (p=0.01), but
      only in females. This is the first study associating mitochondrial DNA variation
      with both mitochondrial function and neurobehavioral outcomes after TBI in
      humans. Our findings indicate that mitochondrial DNA variation may impact patient
      outcomes after a TBI potentially by influencing mitochondrial function, and that
      sex of the patient may be important in evaluating these associations in future
      studies.

PMID- 23883113
TI  - Topological, geometric, and chemical order in materials: insights from solid
      state NMR.
AB  - Unlike the long-range order of ideal crystalline structures, local order is an
      intrinsic characteristic of real materials and often serves as the key to the
      tuning of their properties and their final applications. Although researchers can
      easily assess local ordering using two-dimensional imaging techniques with
      resolution that approaches the atomic level, the diagnosis, description, and
      qualification of local order in three dimensions is much more challenging. Solid
      state nuclear magnetic resonance (NMR) and its panel of continually developing
      instruments and methods enable the local, atom-selective characterization of
      structures and assemblies ranging from the atomic to the nanometer length scales.
      By making use of the indirect J-coupling that distinguishes chemical bonds,
      researchers can use solid-state NMR to characterize a variety of materials,
      ranging from crystalline compounds to amorphous or glassy materials. In
      crystalline compounds showing some disorder, we describe and distinguish the
      contributions of topology, geometry, and local chemistry in ways that are
      consistent with X-ray diffraction and computational approaches. We give examples
      of materials featuring either chemical disorder in a topological order or
      topological disorder with local chemical order. For glasses, we show that we can
      separate geometric and chemical contributions to the local order by identifying
      structural motifs with a viewpoint that extends from the atomic scale up to the
      nanoscale. As identified by solid state NMR, the local structure of amorphous
      materials or glasses consists of well-identified structural entities up to at
      least the nanometer scale. Instead of speaking of disorder, we propose a new
      description for these structures as a continuous assembly of locally defined
      structures, an idea that draws on the concept of locally favored structures (LFS)
      introduced by Tanaka and coworkers. This idea provides a comprehensive picture of
      amorphous structures based on fluctuations of chemical composition and structure
      over different length scales. We hope that these local or molecular insights will
      allow researchers to consider key questions related to nucleation and
      crystallization, as well as chemically (spinodal decomposition) or density-driven
      (polyamorphism) phase separation, which could lead to future applications in a
      variety of materials. 

PMID- 23883114
TI  - Star polymer unimicelles on graphene oxide flakes.
AB  - We report the interfacial assembly of amphiphilic heteroarm star copolymers
      (PSnP2VPn and PSn(P2VP-b-PtBA)n (n = 28 arms)) on graphene oxide flakes at the
      air-water interface. Adsorption, spreading, and ordering of star polymer micelles
      on the surface of the basal plane and edge of monolayer graphene oxide sheets
      were investigated on a Langmuir trough. This interface-mediated assembly resulted
      in micelle-decorated graphene oxide sheets with uniform spacing and organized
      morphology. We found that the surface activity of solvated graphene oxide sheets
      enables star polymer surfactants to subsequently adsorb on the presuspended
      graphene oxide sheets, thereby producing a bilayer complex. The positively
      charged heterocyclic pyridine-containing star polymers exhibited strong affinity
      onto the basal plane and edge of graphene oxide, leading to a well-organized and
      long-range ordered discrete micelle assembly. The preferred binding can be
      related to the increased conformational entropy due to the reduction of interarm
      repulsion. The extent of coverage was tuned by controlling assembly parameters
      such as concentration and solvent polarity. The polymer micelles on the basal
      plane remained incompressible under lateral compression in contrast to ones on
      the water surface due to strongly repulsive confined arms on the polar surface of
      graphene oxide and a preventive barrier in the form of the sheet edges. The
      densely packed biphasic tile-like morphology was evident, suggesting the high
      interfacial stability and mechanically stiff nature of graphene oxide sheets
      decorated with star polymer micelles. This noncovalent assembly represents a
      facile route for the control and fabrication of graphene oxide-inclusive
      ultrathin hybrid films applicable for layered nanocomposites. 

PMID- 23883112
TI  - Milk is not just food but most likely a genetic transfection system activating
      mTORC1 signaling for postnatal growth.
AB  - Milk has been recognized to represent a functionally active nutrient system
      promoting neonatal growth of mammals. Cell growth is regulated by the nutrient
      sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is
      still a lack of information on the mechanisms of mTORC1 up-regulation by milk
      consumption. This review presents milk as a materno-neonatal relay system
      functioning by transfer of preferential amino acids, which increase plasma levels
      of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1
      (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1)
      for mTORC1 activation. Importantly, milk exosomes, which regularly contain
      microRNA-21, most likely represent a genetic transfection system enhancing mTORC1
      driven metabolic processes. Whereas human breast milk is the ideal food for
      infants allowing appropriate postnatal growth and species-specific metabolic
      programming, persistent high milk signaling during adolescence and adulthood by
      continued cow's milk consumption may promote mTORC1-driven diseases of
      civilization. 

PMID- 23883115
TI  - Influence of low-level laser therapy on the rate of orthodontic movement: a
      literature review.
AB  - OBJECTIVE: The purpose of this study was to review low-level laser therapy (LLLT)
      protocols that have been used to date, and to indicate which parameters appear to
      be most effective to guide future research. BACKGROUND DATA: Studies assessing
      the influence of LLLT on the rate of orthodontic tooth movement have produced
      controversial results as a result of methodological differences. METHODS: The
      MEDLINE((r)) database (1975-2012) and the Cochrane library (subject 8) were
      reviewed. Clinical studies and animal experiments written in English and focusing
      on the effects of LLLT on the rate of orthodontic movement were browsed. Article
      selection was conducted by one reviewer and checked by a second investigator.
      RESULTS: A total of 109 articles were identified, of which 14 were selected for
      detailed analysis. Diode laser was used in all studies with different energies,
      frequencies, and doses. In animal studies, the most common and effective energy
      input was 54 J per session daily; in humans, it was 2 J per session on the first
      days of each month, with 72-96 h intervals. Orthodontic force also influenced
      orthodontic movement. A force of 10 g/force seems to be indicated for moving
      molars in rats, versus 150 g for canines in humans. CONCLUSIONS: Most authors
      report positive effects of the use of LLLT on speed increase of orthodontic tooth
      movement when compared with control or placebo groups. Diode laser, especially
      gallium aluminum arsenide, used continuously and in direct contact with the
      irradiated areas, was the most frequent protocol. Further studies are warranted
      to determine the best protocols with regard to energy, dose, and intervention
      schedule.

PMID- 23883118
TI  - What is the best way to deliver therapeutics and who decides?

PMID- 23883116
TI  - Regimen-specific effects of RNA-modified chimeric antigen receptor T cells in
      mice with advanced leukemia.
AB  - Cytotoxic T lymphocytes modified with chimeric antigen receptors (CARs) for
      adoptive immunotherapy of hematologic malignancies have demonstrated activity in
      early phase clinical trials. While T cells bearing stably expressed CARs are
      efficacious and have potential long-term persistence, temporary expression of a
      CAR via RNA electroporation is also potentially efficacious in preclinical
      models. Temporary CAR expression using RNA presents a method of testing CARs
      clinically with additional safety where there may be concerns about possible
      chronic "on-target, off-tumor" toxic effects, as the degradation of RNA ensures
      complete removal of the CAR over time without relying on suicide induction
      systems. CD19-directed RNA CAR T cells were tested in vivo for efficacy and
      comparison to lentiviral vector (LV)-generated stable CAR T cells. We tested the
      hypothesis that multiple infusions of RNA CAR T cells preceded by lymphodepleting
      chemotherapy could mediate improved survival and sustained antitumor responses in
      a robust leukemia xenograft model. The saturation strategy using rationally
      designed multiple infusions of RNA CARs based on multiple model iterations
      approached the efficacy of a stable LV expression method. Two-color imaging
      revealed that relapse was a locoregional phenomenon in both the temporary and the
      stable expression models. In marked contrast to stably expressed CARs with
      retroviral or LV technology, the efficacy of RNA CARs appears independent of the
      costimulatory signaling endodomains likely because they more influence
      proliferation and persistence rather than short-term efficacy. The efficacy of
      the RNA CAR infusions may approach that of stably expressed CARs, offer
      theoretically safer initial clinical testing in addition to suicide systems, and
      allow for rapid and effective iterative preclinical modeling for the testing of
      new targets.

PMID- 23883117
TI  - Focused ultrasonic propulsion of kidney stones: review and update of preclinical
      technology.
AB  - INTRODUCTION: A noninvasive tool to reposition kidney stones could have
      significant impact in the management of stone disease. Our research group has
      developed a noninvasive transcutaneous ultrasound device. A review and update of
      the current status of this technology is provided. DISCUSSION OF TECHNOLOGY:
      Stone propulsion is achieved through short bursts of focused, ultrasonic pulses.
      The initial system consisted of an eight-element annular array transducer,
      computer, and separate ultrasound imager. In the current generation, imaging and
      therapy are completed with one ultrasound system and a commercial probe. This
      generation allows real-time ultrasound imaging, targeting, and propulsion. Safety
      and effectiveness for the relocation of calyceal stones have been demonstrated in
      the porcine model. ROLE IN ENDOUROLOGY: This technology may have applications in
      repositioning stones as an adjunct to lithotripsy, facilitating clearance of
      residual fragments after lithotripsy, expelling de novo stones, and potentially
      repositioning obstructing stones. Human trials are in preparation.

PMID- 23883119
TI  - Improving DNA vaccines against malaria: could immunization by gene gun be the
      answer?

PMID- 23883120
TI  - Targeting nanotherapeutics to the tumor microenvironment: how accurately can we
      aim?

PMID- 23883123
TI  - Applications of ultrasound for image-guided drug delivery in cancer chemotherapy.
AB  - Many challenges persist in the field of cancer drug delivery. The field of image
      guided drug delivery emerged from the need for accurate in vivo quantification of
      various pharmacokinetic and therapeutic delivery parameters. Today it continues
      to be an essential tool in delivery system R&D while providing innovative
      noninvasive strategies for advancement. This article will focus specifically on
      the role of ultrasound in this area. Ultrasound provides a novel means by which
      drugs can be delivered through guided placement of a local delivery device, or
      through the destruction of ultrasound contrast agents at the target location. The
      techniques developed by our research group have examined these areas and have
      also led to a more thorough understanding into the parameters that affect drug
      release kinetics in vivo from in situ-forming implants. In addition, we have
      developed a new ultrasound contrast agent capable of extravascular delivery to
      tumors for improved detection and eventual treatment. Both areas will be
      discussed in this research spotlight. 

PMID- 23883125
TI  - Recent advances in porous silicon technology for drug delivery.
AB  - Porous silicon (pSi) is a nanostructured carrier system that has received
      considerable attention over the past 10 years, for use in a wide variety of
      biomedical applications, including biosensing, biomedical imaging, tissue
      scaffolds and drug delivery. This interest is due to several key features of pSi,
      including excellent in vivo biocompatibility, the ease of surface chemistry
      modification and the control over its 3D porous network structure. With control
      of these physical parameters pSi has successfully been used for the delivery of a
      variety of therapeutics, ranging from small-molecule drugs to larger
      peptide/protein-type therapeutics. In this review, the authors provide a brief
      overview of pSi fabrication methods, particularly with regard to the need to
      passivate the highly reactive Si-Hx surface species of native pSi, typically via
      thermal oxidation, hydrocarbonization or hydrosilylation. This surface
      modification, in turn, controls both the loading and release of therapeutics. The
      authors will then report on specific case studies of leading examples on the use
      of pSi as a therapeutic-delivery system. Specifically, the first reported in vivo
      study that demonstrated the use of pSi to improve the delivery of a
      Biopharmaceutical Classification System Class 2 poorly soluble drug
      (indomethacin), by using thermally oxidized pSi, is discussed, as well as
      highlighting a study that determined the biodistribution of (18)F-radiolabeled
      thermally hydrocarbonized pSi after oral dosing. The authors also report on the
      development of composite pSi-poly(D,L-lactide-co-glycolide) microparticles for
      the controlled delivery of protein therapeutics. Finally, the use of pSi in the
      delivery of bioactives, such as the successful use of thermally carbonized pSi to
      deliver Melanotan II, an unspecific agonist for the melanocortin receptors that
      are involved in controlling fluid uptake is discussed. With a growing body of
      literature reporting the successful use of pSi to deliver a range of
      therapeutics, we are entering what may be a golden age for this drug-delivery
      system, which may finally see the long-held promises finally achieved. 

PMID- 23883127
TI  - Nanoemulsion-based oral delivery systems for lipophilic bioactive components:
      nutraceuticals and pharmaceuticals.
AB  - Nanoemulsions have considerable potential for encapsulating, protecting and
      delivering lipophilic bioactive components via the oral route, such as
      pharmaceuticals (drugs) and nutraceuticals (food components with specific health
      benefits). These systems can be fabricated from generally recognized as safe
      ingredients using relatively simple processing operations, such as mixing and
      homogenization. Some of the potential advantages of nanoemulsions over
      conventional emulsions include higher bioaccessibility, higher physical stability
      and higher optical clarity. An overview of the current status of nanoemulsion
      fabrication, stability, properties and biological fate is given, with special
      emphasis on the suitability of nanoemulsions for the oral delivery of hydrophobic
      bioactive components, such as drugs and nutraceuticals. 

PMID- 23883124
TI  - Oligonucleotide conjugates for therapeutic applications.
AB  - Insufficient pharmacokinetic properties and poor cellular uptake are the main
      hurdles for successful therapeutic development of oligonucleotide agents. The
      covalent attachment of various ligands designed to influence the biodistribution
      and cellular uptake or for targeting specific tissues is an attractive
      possibility to advance therapeutic applications and to expand development
      options. In contrast to advanced formulations, which often consist of multiple
      reagents and are sensitive to a variety of preparation conditions,
      oligonucleotide conjugates are defined molecules, enabling structure-based
      analytics and quality control techniques. This review gives an overview of
      current developments of oligonucleotide conjugates for therapeutic applications.
      Attached ligands comprise peptides, proteins, carbohydrates, aptamers and small
      molecules, including cholesterol, tocopherol and folic acid. Important linkage
      types and conjugation methods are summarized. The distinct ligands directly
      influence biochemical parameters, uptake mechanisms and pharmacokinetic
      properties.

PMID- 23883128
TI  - Metallic nanoparticles and their medicinal potential. Part I: gold and silver
      colloids.
AB  - The article highlights the synthesis, properties and recent advances in
      therapeutic possibilities of metallic nanoparticles. Nanometallic structures that
      behave as drug-carrying agents, gene regulators, imaging agents and
      photoresponsive assemblies have been discussed in the context of cells and many
      debilitating diseases. These structures not only act as alternatives to molecule
      based systems, but also possess new physical and chemical properties, which
      confer substantive advantages in medicinal field. 

PMID- 23883126
TI  - Engineering antiphagocytic biomimetic drug carriers.
AB  - Drug-delivery carriers have the potential to not only treat but also diagnose
      many diseases; however, they still lack the complexity of natural-particulate
      systems. Cell-based therapies using tumor-targeting T cells and tumor-homing
      mesenchymal stem cells have given researchers a means to exploit the
      characteristics exhibited by innate-biological entities. Similarly, immune
      evasion by pathogens has inspired the development of natural polymers to cloak
      drug carriers. The 'marker-of-self' CD47 protein, which is found ubiquitously on
      mammalian cell surfaces, has been used for evading phagocyte clearance of drug
      carriers. This review will focus on the recent progress of drug carriers co
      opting the tricks that cells in nature use to hide safely under the radar of the
      body's innate immune system. 

PMID- 23883130
TI  - New [PbBi2O4][Bi2O2]Cl2 and [Pb(n)Bi(10-n)O13][Bi2O2](n)Cl(4+n) series by
      association of sizable subunits: relationship with Arppe's compound Bi24O31Cl10
      and luminescence properties.
AB  - Four new mixed lead-bismuth oxychloride compounds have been prepared and
      characterized by single crystal X-ray diffraction. Their crystal structures are
      described on the basis of the association of distinct building units found in
      parent Pb or Bi oxychlorides. The new compound PbBi4O6Cl2 is formed of the
      stacking of 2D positive [Bi2O2](2+) layers and neutral [PbBi2O4](0) double layers
      separated by Cl(-) anions. Similar motifs with finite lengths are combined
      together in the new series [Pb(n)Bi(10-n)O13][Bi2O2](n)Cl(4+n). From the
      structural viewpoint, it is striking that this family of homologous phases is
      strongly related to Bi24O31Cl10 well-known as Arppe's compound in which the
      fluorite-like [Bi2O2]n subunit was increased from n = 1 (mixed Bi/Pb Arppe's
      compound) to n = 2, 3, and 4 new members. The preparation of the respective
      powders shows the predominant stability of the n = 2 term which was prepared as a
      single-phase, while other terms have not been obtained in absence of secondary
      phases. For n = 2, the impedance spectroscopy shows a conductivity value sigma ~
      10(-3) S cm(-1) at 650  degrees C and suggests a contribution of Cl(-) in the
      diffusion process. Most remarkable, PbBi4O6Cl2 as well as [Pb2Bi8O13][Bi2O2]2Cl6
      show very bright red emission at low temperature, which could be assigned to
      Bi(3+) transitions by comparison to BaBi4O6Cl2. The different shapes of the
      excitation spectra lead to the assumption of a complete Pb-Bi energy transfer.

PMID- 23883131
TI  - Identifying the catalytic acid/base in GH29 alpha-L-fucosidase subfamilies.
AB  - While the catalytic nucleophile in the configuration-retaining alpha-L
      fucosidases from family GH29 is fully conserved with respect to sequence, there
      is no fully sequence-conserved acid/base residue candidate across the family. X
      ray crystallographic studies and kinetic characterizations have allowed the
      identification of this residue in a few cases, and a recent combination of
      phylogenetic tree analyses with substrate specificity data has allowed the
      division of GH29 enzymes into two subfamilies, A and B, allowing the probable
      assignment of these residues. Here, we perform detailed kinetic and mechanistic
      characterizations of the corresponding alanine mutants and other candidates.
      Through comparison of kinetic parameters obtained for the hydrolysis of fucosyl
      substrates with activated leaving groups by these mutants with those of the
      corresponding wild-type enzymes, in conjunction with the demonstration of azide
      rescue, we largely confirm the acid/base residue predictions for the GH29
      fucosidases from the two subfamilies.

PMID- 23883133
TI  - Gold-catalyzed domino aminocyclization/1,3-sulfonyl migration of N-substituted N
      sulfonyl-aminobut-3-yn-2-ols to 1-substituted 3-sulfonyl-1H-pyrroles.
AB  - A method to prepare 1-substituted 3-sulfonyl-1H-pyrroles efficiently that relies
      on the gold(I)-catalyzed cycloisomerization of N-substituted N-sulfonyl-aminobut
      3-yn-2-ols is described. The method was shown to be applicable to a broad range
      of 1,7-enyne alcohols containing electron-withdrawing, electron-donating, and
      sterically demanding substrate combinations. The mechanism is suggested to
      involve activation of the propargylic alcohol by the Au(I) catalyst, which causes
      the intramolecular nucleophilic addition of the sulfonamide unit to the alkyne
      moiety. The resulting nitrogen-containing heterocyclic intermediate undergoes
      dehydration and deaurative 1,3-sulfonyl migration, a process that remains rare in
      gold catalysis, to give the aromatic nitrogen-containing product. 

PMID- 23883132
TI  - Cyanidin-3-glucoside extracted from mulberry fruit can reduce N-methyl-N
      nitrosourea-induced retinal degeneration in rats.
AB  - PURPOSE: To investigate the effect of cyanidin-3-O-glucoside (C3G) on a rat
      retinal degeneration (RD) model. MATERIALS AND METHODS: Experimental RD was
      induced in rats by the intraperitoneal injection of N-methyl-N-nitrosourea (MNU)
      at 50 mg/kg. C3G extracted from mulberry (Morus alba L.) fruit (50 mg/kg) was
      orally administered, daily for 1, 2 and 4 weeks after MNU injection. The effects
      of C3G administration on MNU-induced RD retinas were histologically and
      functionally assessed by hematoxylin and eosin staining and electroretinography
      (ERG), respectively. The degree of retinal injury in C3G-administered RD rats was
      evaluated by immunohistochemistry with an antibody against glial fibrillary
      acidic protein (GFAP). The preferential protective effect of C3G on scotopic
      vision was examined by western blot analysis. RESULTS: Marked loss of
      photoreceptors in the outer nuclear layer (ONL) was observed in RD rats at 2 and
      4 weeks after MNU injection, while the ONL in the MNU-induced RD rats given C3G
      was relatively well preserved. Immunohistochemistry with anti-GFAP showed that
      retinal injury was also reduced in the retinas of the rats given C3G. Functional
      assessment by using ERG recordings showed that scotopic ERG responses were
      significantly increased in RD rats given C3G for 4 weeks (p < 0.01) compared with
      that of untreated RD rats. In the RD rats given short-term C3G (for 1 and 2
      weeks), the increase in ERG responses was not significant. In addition, western
      blot analysis showed that rhodopsin level in the C3G-administered RD retinas
      significantly increased compared to that in the non-administered RD retinas (p <
      0.05), whereas red/green opsin level did not show any significant difference.
      CONCLUSIONS: Long-term administration of C3G extracted from mulberry fruit could
      structurally reduce photoreceptor damage and functionally improve scotopic visual
      functions in the RD rat model induced by MNU.

PMID- 23883134
TI  - Labeling deoxyadenosine for the preparation of functional conjugated
      oligonucleotides.
AB  - Herein we present a versatile synthetic method for the 8-thioalkylation of
      (deoxy)adenosine with a short carbon linker having on the other side a variety of
      molecules (psoralen, acridine) and functional groups (alkyne). After conventional
      protections, the modified adenosine can be phosphytylated and inserted into an
      oligonucleotide without affecting the standard protocols for supported
      oligonucleotide synthesis. The hybridization properties of a generic
      oligonucleotide containing the above conjugated moieties toward both DNA and RNA
      are evaluated both in the case of a perfectly complementary strand and in the
      case of a single mismatch. This methodology is suitable for the preparation of
      several types of derivatives and-through the alkynyl moiety-provides fast access
      to click-chemistry transformations.

PMID- 23883135
TI  - High-quality, highly concentrated semiconducting single-wall carbon nanotubes for
      use in field effect transistors and biosensors.
AB  - We developed a simple and scalable selective synthesis method of high-quality,
      highly concentrated semiconducting single-wall carbon nanotubes (s-SWCNTs) by in
      situ hydrogen etching. Samples containing ~93% s-SWCNTs were obtained in bulk.
      These s-SWCNTs with good structural integrity showed a high oxidation resistance
      temperature of ~800  degrees C. Thin-film transistors based on the s-SWCNTs
      demonstrated a high carrier mobility of 21.1 cm(2) V(-1) s(-1) at an on/off ratio
      of 1.1 * 10(4) and a high on/off ratio of 4.0 * 10(5) with a carrier mobility of
      7.0 cm(2) V(-1) s(-1). A biosensor fabricated using the s-SWCNTs had a very low
      dopamine detection limit of 10(-18) mol/L at room temperature.

PMID- 23883136
TI  - Nitrogen footprint in China: food, energy, and nonfood goods.
AB  - The nitrogen (N) footprint is a novel approach to quantify losses to the
      environment of reactive N (Nr; all species of N except N2) derived from human
      activities. However, current N footprint models are difficult to apply to new
      countries due to the large data requirement, and sources of Nr included in
      calculating the N footprint are often incomplete. In this study, we
      comprehensively quantified the N footprint in China with an N mass balance
      approach. Results show that the per capita N footprint in China increased 68%
      between 1980 and 2008, from 19 to 32 kg N yr(-1). The Nr loss from the production
      and consumption of food was the largest component of the N footprint (70%) while
      energy and nonfood products made up the remainder in approximately equal portion
      in 2008. In contrast, in 1980, the food-related N footprint accounted for 86% of
      the overall N footprint, followed by nonfood products (8%) and energy (6%). The
      findings and methods of this study are generally comparable to that of the
      consumer-based analysis of the N-Calculator. This work provides policy makers
      quantitative information about the sources of China's N footprint and
      demonstrates the significant challenges in reducing Nr loss to the environment. 

PMID- 23883137
TI  - The effectiveness of individual placement and support for people with mental
      illness new on social benefits: a study protocol.
AB  - BACKGROUND: In Switzerland, people with a severe mental illness and unable to
      work receive disability benefits ('IV-pension'). Once they are granted these
      benefits, the chances to regain competitive employment are usually small.
      However, previous studies have shown that individual placement and support (IPS)
      supports a successful reintegration into competitive employment. This study
      focuses on the integration of newly appointed IV-pensioners, who have received an
      IV-pension for less than a year. METHOD/DESIGN: The present pilot project ZHEPP
      (Zurcher Eingliederungs-Pilot Projekt; engl.: Zurich integration pilot project)
      is a randomized controlled trial (RCT). The 250 participants will be randomized
      to either the intervention or the control group. The intervention group receives
      support of a job coach according to the approach of IPS. Participants in the
      control group do not receive IPS support. Participation takes a total of two
      years for each participant. Each group is interviewed every six months (T0-T4). A
      two-factor analysis of variance will be conducted with the two factors group
      (intervention versus control group) and outcome (employment yes/no). The main
      criterion of the two-factor analysis will be the number of competitive employment
      contracts in each group. DISCUSSION: This study will focus on the impact of IPS
      on new IV-pensioners and aims to identify predictors for a successful
      integration. Furthermore, we will examine the effect of IPS on stigma variables
      and recovery orientation. TRIAL REGISTRATION: ISRCTN54951166.

PMID- 23883138
TI  - The Good Schools Toolkit to prevent violence against children in Ugandan primary
      schools: study protocol for a cluster randomised controlled trial.
AB  - BACKGROUND: We aim to evaluate the effectiveness of the Good School Toolkit,
      developed by Raising Voices, in preventing violence against children attending
      school and in improving child mental health and educational outcomes.
      METHODS/DESIGN: We are conducting a two-arm cluster randomised controlled trial
      with parallel assignment in Luwero District, Uganda. We will also conduct a
      qualitative study, a process evaluation and an economic evaluation. A total of 42
      schools, representative of Luwero District, Uganda, were allocated to receive the
      Toolkit plus implementation support, or were allocated to a wait-list control
      condition. Our main analysis will involve a cross-sectional comparison of the
      prevalence of past-week violence from school staff as reported by children in
      intervention and control primary schools at follow-up.At least 60 children per
      school and all school staff members will be interviewed at follow-up. Data
      collection involves a combination of mobile phone-based, interviewer-completed
      questionnaires and paper-and-pen educational tests. Survey instruments include
      the ISPCAN Child Abuse Screening Tools to assess experiences of violence; the
      Strengths and Difficulties Questionnaire to measure symptoms of common childhood
      mental disorders; and word recognition, reading comprehension, spelling,
      arithmetic and sustained attention tests adapted from an intervention trial in
      Kenya. DISCUSSION: To our knowledge, this is the first study to rigorously
      investigate the effects of any intervention to prevent violence from school staff
      to children in primary school in a low-income setting. We hope the results will
      be informative across the African region and in other settings. TRIAL
      REGISTRATION: clinicaltrials.gov NCT01678846.

PMID- 23883139
TI  - Serum IL-10 as a marker of severe dengue infection.
AB  - BACKGROUND: Several studies have shown that serum IL-10, IFNgamma and MIF are
      elevated in patients in severe dengue (SD) and could be used as potential
      biomarkers. We proceeded to determine if these cytokines could be used as
      biomarkers in a large cohort of adult dengue patients with varying severity of
      dengue infection. METHODS: Serum IL-10 levels were determined in 259 of whom 40
      had severe dengue infection. Serum IFNgamma and IFNalpha levels were done in 78
      and MIF levels were done in 65 patients with acute dengue infection. Clinical
      features and laboratory investigations were undertaken during the febrile and
      critical phase. RESULTS: We found that serum IL-10 levels were significantly
      higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum
      IL-10 levels significantly and inversely correlated with white cell counts (R = 
      0.23, p = 0.0002) and lymphocyte counts (R = -0.29, p < 0.0001) but significantly
      and positively correlated with aspartate tranaminase levels (R = 0.16, p = 0.01)
      and alanine transaminase levels (R = 0.22, p = 0.007). However, IL-10 levels did
      not have a good predictive value in discriminating those who were likely to
      develop SD (AUC = 0.66). Serum IFNgamma levels were also significantly higher (p
      = 0.04) in patients with SD when compared to non SD. There was no difference (p =
      0.34) in serum IFNalpha levels and serum MIF levels (p = 0.15) in patients with
      SD and non SD. CONCLUSION: Although serum IL-10 was significantly elevated in
      patients with SD it had a poor discriminatory value in identifying those with SD
      and non SD and therefore, is unsuitable to be used as a robust biomarker in this
      cohort.

PMID- 23883140
TI  - White matter disintegration in cluster headache.
AB  - BACKGROUND: Previous studies in primary headache disorders showed microstructural
      alterations in the white matter as measured by diffusion imaging. However these
      investigations are not in full agreement and some of those, especially in cluster
      headache, restricted the analysis to only a limited number of diffusion
      parameters. Therefore, in the current study we examined white matter
      microstructure in cluster headache patients. METHODS: Diffusion weighted MRI
      images with 60 directions were acquired from thirteen patients with cluster
      headache and sixteen age-matched healthy controls. Tract based spatial statistics
      were used to compare white matter integrity in the core of the fibre bundles.
      Correlation of the diffusion parameters with cumulative number of headache days
      was examined. RESULTS: There was a significant increment of the mean, axial and
      perpendicular diffusivity in widespread white matter regions in the frontal,
      parietal, temporal and occipital lobes. Reduced fractional anisotropy was found
      in the corpus callosum and some frontal and parietal white matter tracts mainly
      in the contralateral side of the pain. Axial diffusivity showed negative
      correlation to the number of the headache attacks. CONCLUSIONS: The in vivo
      analysis of microstructural alterations in cluster headache provides important
      features of the disease, which might offer a deeper insight into the
      pathomechanism of the disease.

PMID- 23883141
TI  - Severe recurrent rhabdomyolysis-induced acute kidney injury in a HIV-infected
      patient on antiretroviral therapy.
AB  - Antiretroviral medications, specifically tenofovir, have been linked to acute
      tubular necrosis in humans with a suggested mechanism of direct tubular injury.
      Rhabdomyolysis has rarely been described in patients on highly active
      antiretroviral therapy (HAART). To the best of our knowledge, severe recurrent
      rhabdomyolysis-induced acute kidney injury (AKI) in a HIV-infected patient on two
      different triple antiretroviral regimens has not been reported. We present a HIV
      positive patient who first developed heme pigment-induced oliguric AKI due to non
      traumatic rhabdomyolysis, 5 days after initiation of triple antiretroviral
      therapy. Renal function normalized 2 months after discontinuation of
      antiretroviral therapy. Two weeks after reinitiating a different HAART regimen,
      our patient developed a recurrent episode of severe rhabdomyolysis-induced AKI.
      Both rhabdomyolysis and AKI resolved after discontinuation of the second
      antiretroviral regimen. First tenofovir and subsequently abacavir seem to be the
      likely culprits in our case. We also briefly discuss tenofovir nephrotoxicity
      followed by a literature review on rhabdomyolysis in HIV-infected patients.

PMID- 23883142
TI  - An FeF(3).0.5H2O polytype: a microporous framework compound with intersecting
      tunnels for Li and Na batteries.
AB  - To improve the energy/power density of energy storage materials, numerous efforts
      have focused on the exploration of new structure prototypes, in particular metal
      organic fameworks, Prussian blue analogues, open-framework oxides, and polyanion
      salts. Here we report a novel pyrochlore phase that appears to be useful as a
      high-capacity cathode for Li and Na batteries. It is an iron fluoride polymorph
      characterized by an intersecting tunnel structure, providing the space for
      accommodation and transport of Li and Na ions. It is prepared using hydrolyzable
      ionic liquids, which serve as reaction educts and structure-directing agents not
      only as far as the chemical structure is concerned but also in terms of
      morphology (shape, defect structure, electrode network structure). A capacity
      higher than 220 mA h g(-1) (for Li and Na storage) and a lifetime of at least 300
      cycles (for Li storage) are demonstrated. 

PMID- 23883143
TI  - Exploring perceptions of occupational competence among participants in Individual
      Placement and Support (IPS).
AB  - OBJECTIVE: The purpose of this study was to explore perceptions of occupational
      competence and occupational value among a group of clients engaged in Individual
      Placement and Support (IPS). METHODS: The Occupational Self-Assessment (OSA),
      based on the Model of Human Occupation, was used with 65 men and women with
      mental illness, and 45 of these completed the study. RESULTS: Rasch analyses
      showed that the participants perceived "Managing my finances", "Managing my basic
      needs", and "Doing activities I like" as the most valued occupations. Most
      competence was perceived in "Taking care of myself". Among the occupations where
      the participants perceived least competence, "Getting done what I need to do" and
      "Accomplishing what I set out to do" were the occupations that most stand out.
      Significant differences were also found between perceived competence and value in
      most of the occupations. CONCLUSIONS: Beyond those occupations valued as most
      important among the participants, it is essential also to pay attention to those
      in which they perceived least competence, as they are important for being able to
      achieve a desired occupation. Support related to perceptions of occupational
      competence can contribute to enabling clients in IPS to master a desired working
      life.

PMID- 23883144
TI  - Physical activity among Norwegian adolescents--a multilevel analysis of how place
      of residence is associated with health behaviour: the Young-HUNT study.
AB  - INTRODUCTION: The purpose of this article is to investigate whether and to what
      degree participation in physical activity among adolescents is associated with
      area economic deprivation in the municipality where they live. In the study we
      took account of aggregated informal social capital at the municipality level and
      compositional effects due to spatial concentration of individual variables known
      to be associated with physical activity. These include informal social
      participation, participation in other cultural activities, and family affluence.
      METHODS: The study was based on a secondary analysis of data from the Norwegian
      HUNT study and municipality characteristics from the Norwegian Social Science
      Data Service 'Commune Database' from 2006. The sample consisted of 8114
      adolescents whose ages ranged from 13 to 19. The explanatory power of the
      independent variables on the dependent variable was assessed using a multilevel
      analysis in which individuals comprised the first level and were nested within
      the municipality level. RESULTS: The average level of physical activity was not
      negatively associated with the level of area economic deprivation when we
      adjusted for informal social participation at the community level. Adjusting for
      area economic deprivation, we found that informal social participation at the
      community level was associated with a higher level of participation in physical
      activity at p< .01. CONCLUSION: For adolescents in a given municipality, informal
      social participation is more strongly associated with a higher level of physical
      activity than the degree of area economic deprivation. This finding supports our
      social capital hypothesis, which states that the amount of social capital is
      strengthening the individual's ability to take part in physical activity.

PMID- 23883145
TI  - Effects of micronized okara dietary fiber on cecal microbiota, serum cholesterol
      and lipid levels in BALB/c mice.
AB  - Micronized by a dry grinding method (D-ODF) or a wet granulating method (W-ODF),
      okara dietary fiber (ODF), was fed to BALB/c mice for 28 d. The water holding
      capacity of D-ODF and W-ODF was significantly enhanced after micronization. W-ODF
      had a larger swell capacity and a higher content of soluble dietary fiber than
      crude ODF and D-ODF. After feeding for 28 d, the populations of Escherichia coli
      and Lactobacilli in the cecum were significantly lower and higher in the W-ODF
      group than other groups, respectively, while the population of Bifidobacterium
      increased in all groups. The effect of each diet on the population of E. coli.
      Lactobacilli and Bifidobacterium was all maintained for a short period of time
      except that the effectiveness of W-ODF diet on the Bifidobacterium population
      lasted slightly longer than other diets. At the end of the feeding period, serum
      total cholesterol (TC) and triglyceride in D-ODF and W-ODF diets were
      significantly lower and HDL-C/TC ratio was significantly higher than those in
      crude ODF.

PMID- 23883147
TI  - Scope of palliative care in relation to chronic disease.

PMID- 23883146
TI  - Research priorities in geriatric palliative care: informal caregiving.
AB  - BACKGROUND: Informal care provided by family members is an essential feature of
      health care systems worldwide. Although caregiving often begins early in the
      disease process, over time informal caregivers must deal with chronic,
      debilitating, and life-threatening illnesses. Despite thousands of published
      studies on informal care, little is known about the intersection of informal
      caregiving and formal palliative care. OBJECTIVE: The goal of this review is to
      identify research priorities that would enhance our understanding of the
      relationship between informal caregiving and palliative care. DESIGN: To better
      understand palliative care in the context of caregiving, we provide an overview
      of the nature of a caregiving career from inception to care recipient placement
      and death and the associated tasks, challenges, and health effects at each stage
      of a caregiving career. This in turn leads to key unanswered questions designed
      to advance research in caregiving and palliative care. RESULTS: Little is known
      about the extent to which and how palliative care uniquely affects the caregiving
      experience. This suggests a need for more fine-grained prospective studies that
      attempt to clearly delineate the experience of caregivers during palliative and
      end-of-life phases, characterize the transitions into and out of these phases
      from both informal and formal caregiver perspectives, identify caregiver needs at
      each phase, and identify effects on key caregiver and patient outcomes.
      CONCLUSIONS: Inasmuch as most caregivers must deal with chronic, debilitating,
      and often life-threatening conditions, it is essential that we advance a research
      agenda that addresses the interplay between informal care and formal palliative
      care.

PMID- 23883148
TI  - Antithyroid drugs and their analogues: synthesis, structure, and mechanism of
      action.
AB  - Thyroid hormones are essential for the development and differentiation of all
      cells of the human body. They regulate protein, fat, and carbohydrate metabolism.
      In this Account, we discuss the synthesis, structure, and mechanism of action of
      thyroid hormones and their analogues. The prohormone thyroxine (T4) is
      synthesized on thyroglobulin by thyroid peroxidase (TPO), a heme enzyme that uses
      iodide and hydrogen peroxide to perform iodination and phenolic coupling
      reactions. The monodeiodination of T4 to 3,3',5-triiodothyronine (T3) by selenium
      containing deiodinases (ID-1, ID-2) is a key step in the activation of thyroid
      hormones. The type 3 deiodinase (ID-3) catalyzes the deactivation of thyroid
      hormone in a process that removes iodine selectively from the tyrosyl ring of T4
      to produce 3,3',5'-triiodothyronine (rT3). Several physiological and pathological
      stimuli influence thyroid hormone synthesis. The overproduction of thyroid
      hormones leads to hyperthyroidism, which is treated by antithyroid drugs that
      either inhibit the thyroid hormone biosynthesis and/or decrease the conversion of
      T4 to T3. Antithyroid drugs are thiourea-based compounds, which include
      propylthiouracil (PTU), methimazole (MMI), and carbimazole (CBZ). The thyroid
      gland actively concentrates these heterocyclic compounds against a concentration
      gradient. Recently, the selenium analogues of PTU, MMI, and CBZ attracted
      significant attention because the selenium moiety in these compounds has a higher
      nucleophilicity than that of the sulfur moiety. Researchers have developed new
      methods for the synthesis of the selenium compounds. Several experimental and
      theoretical investigations revealed that the selone (C?Se) in the selenium
      analogues is more polarized than the thione (C?S) in the sulfur compounds, and
      the selones exist predominantly in their zwitterionic forms. Although the
      thionamide-based antithyroid drugs have been used for almost 70 years, the
      mechanism of their action is not completely understood. Most investigations have
      revealed that MMI and PTU irreversibly inhibit TPO. PTU, MTU, and their selenium
      analogues also inhibit ID-1, most likely by reacting with the selenenyl iodide
      intermediate. The good ID-1 inhibitory activity of PTU and its analogues can be
      ascribed to the presence of the -N(H)-C(?O)- functionality that can form hydrogen
      bonds with nearby amino acid residues in the selenenyl sulfide state. In addition
      to the TPO and ID-1 inhibition, the selenium analogues are very good
      antioxidants. In the presence of cellular reducing agents such as GSH, these
      compounds catalytically reduce hydrogen peroxide. They can also efficiently
      scavenge peroxynitrite, a potent biological oxidant and nitrating agent. 

PMID- 23883149
TI  - Do fibrin sealants impact negative outcomes after robot-assisted partial
      nephrectomy?
AB  - PURPOSE: Contemporary rates of postoperative hemorrhage after partial nephrectomy
      (PN) are low. Commercially available hemostatic agents are commonly used during
      this surgery to reduce this risk despite a paucity of data supporting the
      practice. We assessed the impact of fibrin sealant hemostatic agents, a costly
      addition to surgeries, during robot-assisted partial nephrectomy (RAPN). PATIENTS
      AND METHODS: Between 2007 and 2011, 114 consecutive patients underwent RAPN by a
      single surgeon (MEA). Evicel fibrin sealant was used in the first 74 patients
      during renorraphy. The last 40 patients had renorraphy performed without the use
      of any hemostatic agents. Clinicopathologic, operative, and complication data
      were compared between groups. Multivariate and univariate logistic regression
      analysis was performed to test the association between the use of fibrin sealants
      and operative outcomes. RESULTS: Patient demographic data and clinical tumor
      characteristics were similar between groups. The use of fibrin sealant did not
      increase operative time (166.3 vs 176.1 minutes, P=0.28), warm ischemia time
      (WIT) (14.4 vs 16.1 minutes, P=0.18), or length of hospital stay (2.6 vs 2.4
      days, P=0.35). The omission of these agents did not increase estimated blood loss
      (116.6 vs 176.1 mL, P=0.8) or postoperative blood transfusion (0% vs 2.5%,
      P=0.17). Univariate analysis demonstrated no association between use of fibrin
      sealants and increased complications (P>0.05). Multivariable logistic regression
      showed no statistically significant predictive value of omission of hemostatic
      agents for perioperative outcomes (P>0.05). CONCLUSION: Perioperative hemorrhage
      and other major complications after contemporary RAPN are rare in experienced
      hands. In our study, the use of fibrin sealants during RAPN does not decrease the
      rate of complications, blood loss, or hospital stay. Furthermore, no impact is
      seen on operative time, WIT, or other negative outcomes. Omitting these agents
      during RAPN could be a safe, effective, cost-saving measure.

PMID- 23883150
TI  - Impact of dietary cadmium sulphide nanoparticles on Danio rerio zebrafish at very
      low contamination pressure.
AB  - To address the impact of cadmium sulphide nanoparticles (CdSNPs) of two different
      sizes (8 and 50 nm), Danio rerio zebrafish were dietary exposed to very low
      doses: 100 or 40 ng CdSNPs/day/g body weight for 36 or 60 days, respectively. The
      results obtained using RAPD-PCR genotoxicity test showed genomic alteration since
      the number of hybridisation sites of the RAPD probes was significantly modified
      after CdSNPs exposure. In addition, selected stress response genes were either
      repressed or upregulated in tissues of CdSNPs-exposed fish. Mitochondrial
      dysfunction was also caused by the presence of CdSNPs in food. Cadmium
      accumulation in fish tissues (brain and muscles) could only be observed after 60
      days of exposure. CdSNPs toxicity was dependent on their size and concentration.

PMID- 23883151
TI  - Temporally overlapped but uncoupled motions in dihydrofolate reductase catalysis.
AB  - Temporal correlations between protein motions and enzymatic reactions are often
      interpreted as evidence for catalytically important motions. Using dihydrofolate
      reductase as a model system, we show that there are many protein motions that
      temporally overlapped with the chemical reaction, and yet they do not exhibit the
      same kinetic behaviors (KIE and pH dependence) as the catalyzed chemical
      reaction. Thus, despite the temporal correlation, these motions are not directly
      coupled to the chemical transformation, and they might represent a different part
      of the catalytic cycle or simply be the product of the intrinsic flexibility of
      the protein. 

PMID- 23883152
TI  - Development of a disease risk prediction model for downy mildew (Peronospora
      sparsa) in boysenberry.
AB  - Downy mildew caused by Peronospora sparsa has resulted in serious production
      losses in boysenberry (Rubus hybrid), blackberry (Rubus fruticosus), and rose
      (Rosa sp.) in New Zealand, Mexico, and the United States and the United Kingdom,
      respectively. Development of a model to predict downy mildew risk would
      facilitate development and implementation of a disease warning system for
      efficient fungicide spray application in the crops affected by this disease.
      Because detailed disease observation data were not available, a two-step approach
      was applied to develop an empirical risk prediction model for P. sparsa. To
      identify the weather patterns associated with a high incidence of downy mildew
      berry infections (dryberry disease) and derive parameters for the empirical
      model, classification and regression tree (CART) analysis was performed. Then,
      fuzzy sets were applied to develop a simple model to predict the disease risk
      based on the parameters derived from the CART analysis. High-risk seasons with a
      boysenberry downy mildew incidence >10% coincided with months when the number of
      hours per day with temperature of 15 to 20 degrees C averaged >9.8 over the month
      and the number of days with rainfall in the month was >38.7%. The Fuzzy
      Peronospora Sparsa (FPS) model, developed using fuzzy sets, defined relationships
      among high-risk events, temperature, and rainfall conditions. In a validation
      study, the FPS model provided correct identification of both seasons with high
      downy mildew risk for boysenberry, blackberry, and rose and low risk in seasons
      when no disease was observed. As a result, the FPS model had a significant degree
      of agreement between predicted and observed risks of downy mildew for those crops
      (P = 0.002).

PMID- 23883153
TI  - Phenazine production by Pseudomonas sp. LBUM223 contributes to the biological
      control of potato common scab.
AB  - Common scab of potato is mainly caused by Streptomyces scabies. Currently, no
      method can efficiently control this economically important disease. We have
      previously determined that Pseudomonas sp. LBUM223 exhibits antagonistic
      properties toward S. scabies under in vitro conditions. Inhibition was mainly
      attributed to phenazine-1-carboxylic acid (PCA) production because an isogenic
      mutant of LBUM223 (phzC-), not producing PCA, was incapable of significantly
      reducing S. scabies growth. In order to understand the impact of PCA production
      by LBUM223 in controlling common scab under soil conditions, pot experiments were
      performed to determine its effect on (i) reducing scab symptoms development, (ii)
      S. scabies population dynamics, and (iii) txtA expression in S. scabies, a key
      gene involved in thaxtomin A biosynthesis and required for pathogenesis. Symptoms
      were significantly reduced following inoculation with LBUM223 but not its mutant.
      Surprisingly, pathogen populations increased in the geocaulosphere in the
      presence of both wild-type and mutant strains of LBUM223; however, significant
      repression of txtA expression in S. scabies was only observed in the presence of
      PCA-producing LBUM223, not its mutant. These results suggest that, under soil
      conditions, PCA production by LBUM223 does not control common scab development by
      antibiosis but, instead, reduces S. scabies thaxtomin A production in the
      geocaulosphere, leading to reduced virulence.

PMID- 23883154
TI  - Characterization of management and environmental factors associated with regional
      variations in potato zebra chip occurrence.
AB  - Potato zebra chip (ZC), caused by the bacterial pathogen 'Candidatus Liberibacter
      solanacearum', which is vectored by the potato psyllid (Bactericera cockerelli),
      has caused widespread damage to U.S. potato production ever since its first
      discovery in south Texas in 2000. To determine the influence of environmental
      factors and management practices on ZC occurrence, data on management and
      meteorological variables, field locations, and psyllid counts were collected over
      a 3-year period (2010 to 2012) from six locations across the central United
      States (south Texas to Nebraska). At these locations, ZC-symptomatic plants were
      counted in 26 fields from systematically established 20 m * 30 m plots around the
      field edges and field interiors. Mean numbers of symptomatic plants per plot were
      classified into two intensity classes (ZC <= 3 or ZC > 3) and subjected to
      discriminant function and logistic regression analyses to determine which factors
      best distinguish between the two ZC intensity classes. Of all the variables,
      location, planting date, and maximum temperature were found to be the most
      important in distinguishing between ZC intensity classes. These variables
      correctly classified 88.5% of the fields into either of the two ZC-intensity
      classes. Logistic regression analysis of the individual variables showed that
      location accounted for 90% of the variations, followed by planting date (86%) and
      maximum temperature (70%). There was a low but significant (r = -0.44983, P =
      0.0211) negative correlation between counts of psyllids testing positive for
      pathogen and latitudinal locations, indicating a south-to-north declining trend
      in counts of psyllids testing positive for the pathogen. A similar declining
      trend also was observed in ZC occurrence (r = -0.499, P = 0.0094).

PMID- 23883155
TI  - Viability of 'Candidatus Liberibacter asiaticus' prolonged by addition of citrus
      juice to culture medium.
AB  - Huanglongbing, or citrus greening disease, is associated with infection by the
      phloem-limited bacterium 'Candidatus Liberibacter asiaticus'. Infection with 'Ca.
      L. asiaticus' is incurable; therefore, knowledge regarding 'Ca. L. asiaticus'
      biology and pathogenesis is essential to develop a treatment. However, 'Ca. L.
      asiaticus' cannot currently be successfully cultured, limiting its study. To gain
      insight into the conditions conducive for growth of 'Ca. L. asiaticus' in vitro,
      'Ca. L. asiaticus' inoculum obtained from seed of fruit from infected pomelo
      trees (Citrus maxima 'Mato Buntan') was added to different media, and cell
      viability was monitored for up to 2 months using quantitative polymerase chain
      reaction in conjunction with ethidium monoazide. Media tested included one-third
      King's B (K), K with 50% juice from the infected fruit, K with 50% commercially
      available grapefruit juice, and 100% commercially available grapefruit juice.
      Results show that juice-containing media dramatically prolong viability compared
      with K in experiments reproduced during 2 years using different juice sources.
      Furthermore, biofilm formed at the air-liquid interface of juice cultures
      contained 'Ca. L. asiaticus' cells, though next-generation sequencing indicated
      that other bacterial genera were predominant. Chemical characterization of the
      media was conducted to discuss possible factors sustaining 'Ca. L. asiaticus'
      viability in vitro, which will contribute to future development of a culture
      medium for 'Ca. L. asiaticus'.

PMID- 23883156
TI  - The use of latent class analysis to estimate the sensitivities and specificities
      of diagnostic tests for Squash vein yellowing virus in cucurbit species when
      there is no gold standard.
AB  - Squash vein yellowing virus (SqVYV) is the causal agent of viral watermelon vine
      decline, one of the most serious diseases in watermelon (Citrullus lanatus L.)
      production in the southeastern United States. At present, there is not a gold
      standard diagnostic test for determining the true status of SqVYV infection in
      plants. Current diagnostic methods for identification of SqVYV-infected plants or
      tissues are based on the reverse-transcription polymerase chain reaction (RT
      PCR), tissue blot nucleic acid hybridization assays (TB), and expression of
      visual symptoms. A quantitative assessment of the performance of these diagnostic
      tests is lacking, which may lead to an incorrect interpretation of results. In
      this study, latent class analysis (LCA) was used to estimate the sensitivities
      and specificities of RT-PCR, TB, and visual assessment of symptoms as diagnostic
      tests for SqVYV. The LCA model assumes that the observed diagnostic test
      responses are linked to an underlying latent (nonobserved) disease status of the
      population, and can be used to estimate sensitivity and specificity of the
      individual tests, as well as to derive an estimate of the incidence of disease
      when a gold standard test does not exist. LCA can also be expanded to evaluate
      the effect of factors and was done here to determine whether diagnostic test
      performances varied among the type of plant tissue being tested (crown versus
      vine tissue), where plant samples were taken relative to the position of the
      crown (i.e., distance from the crown), host (i.e., genus), and habitat (field
      grown versus greenhouse-grown plants). Results showed that RT-PCR had the highest
      sensitivity (0.94) and specificity (0.98) of the three tests. TB had better
      sensitivity than symptoms for detection of SqVYV infection (0.70 versus 0.32),
      while the visual assessment of symptoms was more specific than TB and, thus, a
      better indicator of noninfection (0.98 versus 0.65). With respect to the grouping
      variables, RT-PCR and TB had better sensitivity but poorer specificity for
      diagnosing SqVYV infection in crown tissue than it did in vine tissue, whereas
      symptoms had very poor sensitivity but excellent specificity in both tissues for
      all cucurbits analyzed in this study. Test performance also varied with habitat
      and genus but not with distance from the crown. The results given here provide
      quantitative measurements of test performance for a range of conditions and
      provide the information needed to interpret test results when tests are used in
      parallel or serial combination for a diagnosis.

PMID- 23883157
TI  - Sexual reproduction in Aspergillus flavus sclerotia naturally produced in corn.
AB  - Aspergillus flavus is the major producer of carcinogenic aflatoxins worldwide in
      crops. Populations of A. flavus are characterized by high genetic variation and
      the source of this variation is likely sexual reproduction. The fungus is
      heterothallic and laboratory crosses produce ascospore-bearing ascocarps embedded
      within sclerotia. However, the capacity for sexual reproduction in sclerotia
      naturally formed in crops has not been examined. Corn was grown for 3 years under
      different levels of drought stress at Shellman, GA, and sclerotia were recovered
      from 146 ears (0.6% of ears). Sclerotia of A. flavus L strain were dominant in
      2010 and 2011 and sclerotia of A. flavus S strain were dominant in 2012. The
      incidence of S strain sclerotia in corn ears increased with decreasing water
      availability. Ascocarps were not detected in sclerotia at harvest but incubation
      of sclerotia on the surface of nonsterile soil in the laboratory resulted in the
      formation of viable ascospores in A. flavus L and S strains and in homothallic A.
      alliaceus. Ascospores were produced by section Flavi species in 6.1% of the 6,022
      sclerotia (18 of 84 ears) in 2010, 0.1% of the 2,846 sclerotia (3 of 36 ears) in
      2011, and 0.5% of the 3,106 sclerotia (5 of 26 ears) in 2012. For sexual
      reproduction to occur under field conditions, sclerotia may require an additional
      incubation period on soil following dispersal at crop harvest.

PMID- 23883158
TI  - Modeling the effects of environmental conditions on HT2 and T2 toxin accumulation
      in field oat grains.
AB  - Fusarium head blight (FHB) of wheat and barley has been extensively researched
      worldwide; in contrast, there is limited information on the effects of
      environmental conditions on Fusarium toxin accumulation in oat grains. More than
      300 samples of oat grain from various regions of the United Kingdom from 2006 to
      2008 were analyzed for mycotoxin contamination due to infection by Fusarium spp.
      HT2 and T2 toxins were the two most commonly detected, and their concentrations
      in individual samples were highly correlated. Hourly weather data were obtained
      from meteorological recording stations near most of the sampling sites.
      Statistical modeling was applied to both the original toxin (HT2 plus T2) data
      and the toxin data adjusted for oat cultivars and number of cereal crops in the
      previous four seasons. Accumulation of HT2 and T2 toxin was positively correlated
      with warm and wet conditions during early May and dry conditions thereafter.
      Using a collection of 51 environmental variables summarized over three lengths
      (10, 15, and 20 days) of time periods encompassing early May, late May, and early
      July, all-subsets regression showed that many models, consisting of three to six
      predictor variables, could be identified with similar explanatory strength for
      the effect of environmental conditions on toxin accumulation. Most important
      predictor variables were related to wet conditions during the early-May period,
      which was before anthesis. These results suggest that the predominant period for
      Fusarium langsethiae infection of oat is likely to be before rather than during
      anthesis, as for other head blight pathogens. These empirical models may be
      further improved by using quantified pathogen biomass within the grains and
      weather predictor variables summarized in relation to plant growth stages
      (instead of calendar times).

PMID- 23883160
TI  - Pulsed nanogenerator with huge instantaneous output power density.
AB  - A nanogenerator (NG) usually gives a high output voltage but low output current,
      so that the output power is low. In this paper, we developed a general approach
      that gives a hugely improved instantaneous output power of the NG, while the
      entire output energy stays the same. Our design is based on an off-on-off contact
      based switching during mechanical triggering that largely reduces the duration of
      the charging/discharge process, so that the instantaneous output current pulse is
      hugely improved without sacrificing the output voltage. For a vertical contact
      separation mode triboelectric NG (TENG), the instantaneous output current and
      power peak can reach as high as 0.53 A and 142 W at a load of 500 Omega,
      respectively. The corresponding instantaneous output current and power density
      peak even approach 1325 A/m(2) and 3.6 * 10(5) W/m(2), which are more than 2500
      and 1100 times higher than the previous records of TENG, respectively. For the
      rotation disk based TENG in the lateral sliding mode, the instantaneous output
      current and power density of 104 A/m(2) and 1.4 * 10(4) W/m(2) have been
      demonstrated at a frequency of 106.7 Hz. The approach presented here applies to
      both a piezoelectric NG and a triboelectric NG, and it is a major advance toward
      practical applications of a NG as a high pulsed power source. 

PMID- 23883159
TI  - Acoustic streaming enhances the Multicyclic CO2 capture of natural limestone at
      Ca-looping conditions.
AB  - The Ca-Looping (CaL) process, based on the multicyclic carbonation/calcination of
      CaO at high temperatures, is a viable technology to achieve high CO2 capture
      efficiencies in both precombustion and postcombustion applications. In this paper
      we show an experimental study on the multicyclic CO2 capture of a natural
      limestone in a fixed bed at CaL conditions as affected by the application of a
      high-intensity acoustic field. Our results indicate that sound promotes the
      efficiency of CO2 sorption in the fast carbonation phase by enhancing the gas
      solids mass transfer. The fundamentals of the physical mechanism responsible for
      this effect (acoustic streaming) as well as the technical feasibility of the
      proposed technique allows envisaging that sonoprocessing will be beneficial to
      enhance multicyclic CO2 capture in large-scale applications. 

PMID- 23883161
TI  - Effect of naproxen and acetaminophen on blood pressure lowering by ramipril,
      valsartan and aliskiren in hypertensive patients.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used
      for reducing pain and other symptoms in osteoarthritis (OA). NSAIDs have been
      associated with an increase in blood pressure (BP) in both normotensive and
      hypertensive individuals and a blunting effect on various anti-hypertensive
      medications. Acetaminophen effects on anti-hypertensive treatment, instead, are
      still a matter of debate. OBJECTIVES: To assess the effect of naproxen versus
      acetaminophen on ramipril, valsartan and aliskiren therapy in hypertensive
      patients with OA in a double-blind, cross-over study, by measuring clinic,
      ambulatory BP and heart rate (HR). RESULTS: One hundred seventy four patients
      were randomly treated with ramipril, valsartan or aliskiren for 8 weeks and 135
      patients with normalized BP were randomized to receive naproxen or acetaminophen
      for 2 weeks. Naproxen significantly increased clinic and ambulatory
      systolic/diastolic BP (SBP/DBP) values in patients treated with ramipril (p <
      0.01) or valsartan (p < 0.05), but did not affect aliskiren effects. Also
      acetaminophen slightly but significantly affected clinic and ambulatory SBP/DBP
      in all three groups and, surprisingly, it also produced a slight increase in HR
      (+3.1, +3.3 and +3.4 b/min day-time HR values, for ramipril, valsartan and
      aliskiren, respectively; p < 0.05). CONCLUSIONS: Both naproxen and acetaminophen
      can affect anti-hypertensive therapy with ramipril, valsartan or aliskiren with a
      different extent. When acetaminophen is chosen for OA management in subjects with
      hypertension, patients should be evaluated as carefully as when traditional
      NSAIDs are given.

PMID- 23883162
TI  - Effects of Anma massage therapy (Japanese massage) for gynecological cancer
      survivors: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Cancer patients and survivors regularly feel anxious about cancer
      recurrence or death, even after the conclusion of medical treatment, and they are
      often highly physiologically and psychologically stressed. Massage therapy is one
      of the most widely used complementary and alternative therapies used in the hope
      of alleviating such stress and physical and psychological complaints and to
      improve health-related quality of life. This randomized phase III, two-armed,
      parallel group, clinical trial was designed after obtaining positive findings in
      a preliminary study. The primary objective is to verify the effects of continuous
      Japanese massage therapy, referred to as Anma therapy, for cancer survivors. The
      secondary objective is to confirm the immediate effects of a single Anma massage
      session for cancer survivors. METHODS/DESIGN: Sixty cancer survivors older than
      20 years of age who have had histologically confirmed uterine cervical,
      endometrial, ovarian, fallopian tube or peritoneal cancer in the past, but with
      no recurrence for more than 3 years since receiving standard medical treatment,
      are being recruited by gynecologists in medical facilities. In the coordinating
      office, they are randomly allocated to two groups (n = 30 each): an Anma massage
      group receiving a 40-min Anma massage session once weekly over a 2-month
      intervention period (total of eight Anma massage sessions) and a control group
      being followed by medical doctors and receiving no Anma massage sessions. The
      primary end point is the severity of physical subjective symptoms that cancer
      survivors report in daily life, assessed using a Visual Analogue Scale. Secondary
      end points are urine and saliva analyses, psychological condition and health
      related quality-of-life scores as determined on the basis of a self-report
      questionnaire. DISCUSSION: Using the evidence-based findings of this trial,
      medical professionals should be able to explain the benefits conferred by Anma
      massage to cancer survivors and provide higher-quality information to better
      inform patients regarding their decisions about whether to receive such therapy.
      TRIAL REGISTRATION: This trial is registered with the UMIN Clinical Trials
      Registry as UMIN000009097.

PMID- 23883164
TI  - Unusual conformation of a dinuclear paddle wheel copper(II) complex. Synthesis,
      structural characterization and EPR studies.
AB  - An unusual and unique conformation of a paddle wheel type binuclear copper(II)
      complex containing acetate and acetamido ligands, {Cu2(MU2-O2CCH3)4}(OCNH2CH3)
      (1), was obtained by solvothermal synthesis. The structural characterization of
      this compound shows that the apical (acetamido) ligands are disposed at a 62
      degrees  dihedral angle, generating a special conformation as a consequence of
      the synthetic method used. This conformation has not been reported in other
      paddle wheel copper(II) tetraacetate compounds. Electron paramagnetic resonance
      (EPR) spectra of powder samples of (1) were obtained at 9.5 and 33.8 GHz, while
      single crystal spectra were obtained at 33.8 GHz with a B0 applied in three
      orthogonal planes. The fit of the single crystal experimental data allowed gave
      g? = 2.345 +/- 0.003, and g? = 2.057 +/- 0.005. The angular variation of the EPR
      line allows evaluation of the fine structure of (1), giving D = -0.337 +/- 0.002
      cm(-1) and E = -0.005 +/- 0.001 cm(-1). The line width angular dependence, used
      together with the Anderson model and Kubo-Tomita theory, permitted the interdimer
      interaction to be evaluated as |J'| = (0.051 +/- 0.002) cm(-1). Using the powder
      spectral temperature dependence it was possible to evaluate the intradinuclear
      exchange coupling constan J0 as -101 +/- 2 cm(-1), which is considerably lower
      than that reported for other analogous copper(II) tetraacetate paddle wheel
      compounds (Cu(II)-PW), showing the remarkable effect of the conformation of the
      terminal ligands on the magnetic interaction. 

PMID- 23883163
TI  - Decreased APOE-containing HDL subfractions and cholesterol efflux capacity of
      serum in mice lacking Pcsk9.
AB  - BACKGROUND: Studies in animals showed that PCSK9 is involved in HDL metabolism.
      We investigated the molecular mechanism by which PCSK9 regulates HDL cholesterol
      concentration and also whether Pcsk9 inactivation might affect cholesterol efflux
      capacity of serum and atherosclerotic fatty streak volume. METHODS: Mass
      spectrometry and western blot were used to analyze the level of apolipoprotein E
      (APOE) and A1 (APOA1). A mouse model overexpressing human LDLR was used to test
      the effect of high levels of liver LDLR on the concentration of HDL cholesterol
      and APOE-containing HDL subfractions. Pcsk9 knockout males lacking LDLR and APOE
      were used to test whether LDLR and APOE are necessary for PCSK9-mediated HDL
      cholesterol regulation. We also investigated the effects of Pcsk9 inactivation on
      cholesterol efflux capacity of serum using THP-1 and J774.A1 macrophage foam
      cells and atherosclerotic fatty streak volume in the aortic sinus of Pcsk9
      knockout males fed an atherogenic diet. RESULTS: APOE and APOA1 were reduced in
      the same HDL subfractions of Pcsk9 knockout and human LDLR transgenic male mice.
      In Pcsk9/Ldlr double-knockout mice, HDL cholesterol concentration was lower than
      in Ldlr knockout mice and higher than in wild-type controls. In Pcsk9/Apoe double
      knockout mice, HDL cholesterol concentration was similar to that of Apoe knockout
      males. In Pcsk9 knockout males, THP-1 macrophage cholesterol efflux capacity of
      serum was reduced and the fatty streak lesion volume was similar to wild-type
      controls. CONCLUSIONS: In mice, LDLR and APOE are important factors for PCSK9
      mediated HDL regulation. Our data suggest that, although LDLR plays a major role
      in PCSK9-mediated regulation of HDL cholesterol concentration, it is not the only
      mechanism and that, regardless of mechanism, APOE is essential. Pcsk9
      inactivation decreases the HDL cholesterol concentration and cholesterol efflux
      capacity in serum, but does not increase atherosclerotic fatty streak volume.

PMID- 23883165
TI  - Automatic extraction of biomolecular interactions: an empirical approach.
AB  - BACKGROUND: We describe a method for extracting data about how biomolecule pairs
      interact from texts. This method relies on empirically determined characteristics
      of sentences. The characteristics are efficient to compute, making this approach
      to extraction of biomolecular interactions scalable. The results of such
      interaction mining can support interaction network annotation, question
      answering, database construction, and other applications. RESULTS: We constructed
      a software system to search MEDLINE for sentences likely to describe interactions
      between given biomolecules. The system extracts a list of the interaction
      indicating terms appearing in those sentences, then ranks those terms based on
      their likelihood of correctly characterizing how the biomolecules interact. The
      ranking process uses a tf-idf (term frequency-inverse document frequency) based
      technique using empirically derived knowledge about sentences, and was applied to
      the MEDLINE literature collection. Software was developed as part of the MetNet
      toolkit (http://www.metnetdb.org). CONCLUSIONS: Specific, efficiently computable
      characteristics of sentences about biomolecular interactions were analyzed to
      better understand how to use these characteristics to extract how biomolecules
      interact.The text empirics method that was investigated, though arising from a
      classical tradition, has yet to be fully explored for the task of extracting
      biomolecular interactions from the literature. The conclusions we reach about the
      sentence characteristics investigated in this work, as well as the technique
      itself, could be used by other systems to provide evidence about putative
      interactions, thus supporting efforts to maximize the ability of hybrid systems
      to support such tasks as annotating and constructing interaction networks.

PMID- 23883166
TI  - An HD-GYP cyclic di-guanosine monophosphate phosphodiesterase with a non-heme
      diiron-carboxylate active site.
AB  - The intracellular level of the ubiquitous bacterial secondary messenger, cyclic
      di-(3',5')-guanosine monophosphate (c-di-GMP), represents a balance between its
      biosynthesis and degradation, the latter via specific phosphodiesterases (PDEs).
      One class of c-di-GMP PDEs contains a characteristic HD-GYP domain. Here we
      report that an HD-GYP PDE from Vibrio cholerae contains a non-heme diiron
      carboxylate active site, and that only the reduced form is active. An engineered
      D-to-A substitution in the HD dyad caused loss of c-di-GMP PDE activity and of
      two iron atoms. This report constitutes the first demonstration that a non-heme
      diiron-carboxylate active site can catalyze the c-di-GMP PDE reaction and that
      this activity can be redox regulated in the HD-GYP class. 

PMID- 23883167
TI  - Activated singlet exciton fission in a semiconducting polymer.
AB  - Singlet exciton fission is a spin-allowed process to generate two triplet
      excitons from a single absorbed photon. This phenomenon offers great potential in
      organic photovoltaics, but the mechanism remains poorly understood. Most reports
      to date have addressed intermolecular fission within small-molecular crystals.
      However, through appropriate chemical design chromophores capable of
      intramolecular fission can also be produced. Here we directly observe sub-100 fs
      activated singlet fission in a semiconducting poly(thienylenevinylene). We
      demonstrate that fission proceeds directly from the initial 1Bu exciton, contrary
      to current models that involve the lower-lying 2Ag exciton. In solution, the
      generated triplet pairs rapidly recombine and decay through the 2Ag state. In
      films, exciton diffusion breaks this symmetry and we observe long-lived triplets
      which form charge-transfer states in photovoltaic blends. 

PMID- 23883168
TI  - Synthesis of a p-type semiconducting phenothiazine exfoliatable layered crystal.
AB  - Phenothiazine (PTZ) crystals are grown by a physical vapor transport method in a
      horizontal tube furnace. The resulting disk-type PTZ single crystals have a
      layered structure, which can be mechanically exfoliated into stacked individual
      layers to exhibit various colors depending on the thickness. The PTZ single
      crystal field-effect transistor (FET) devices exhibit a p-type semiconducting
      property with 3.03 * 10(-6) S/cm electrical conductivity, 1.15 * 10(-4) cm(2)/(V
      s) carrier mobility, and a 10(4) on/off ratio. 

PMID- 23883169
TI  - Socio-demographic and behavioural correlates of physical activity perception in
      individuals with recently diagnosed diabetes: results from a cross-sectional
      study.
AB  - BACKGROUND: Physical activity (PA) levels in type 2 diabetes mellitus (T2DM)
      patients are generally low. Poor PA perception may impede healthy behaviour
      change in this high risk group. We describe (i) objective PA levels, (ii) the
      difference between objective and self-reported PA ('PA disparity') and the
      correlates of (iii) PA disparity and (iv) overestimation in recently diagnosed
      T2DM patients. METHODS: Cross-sectional analysis of 425 recently diagnosed T2DM
      patients aged 42 to 71, participating in the ADDITION-Plus study in Eastern
      England, UK. We define 'PA disparity' as the non-negative value of the difference
      (in mathematical terms the absolute difference) between objective and self
      reported physical activity energy expenditure (PAEE in kJ . kg-1 . day-1).
      'Overestimators' comprised those whose self-reported- exceeded objective-PAEE by
      4.91 kJ . kg-1 . day-1(the equivalent of 30 minutes moderate activity per day).
      Multivariable linear regression examined the association between PA disparity
      (continuous) and socio-demographic, clinical, health behaviour, quality of life
      and psychological characteristics. Logistic regression examined the association
      between PA overestimation and individual characteristics. RESULTS: Mean objective
      and self-reported PAEE levels +/- SD were 34.4 +/- 17.0 and 22.6 +/- 19.4 kJ . kg
      1.day-1, respectively (difference in means =11.8; 95% CI=9.7 to 13.9 kJ . kg-1 .
      day-1). Higher PA disparity was associated with male sex, younger age, lower
      socio-economic status and lower BMI. PA overestimators comprised 19% (n=80), with
      those in routine/manual occupations more likely to be overestimators than those
      in managerial/professional occupations. CONCLUSIONS: T2DM patients with poor
      physical activity perception are more likely to be male, younger, from a lower
      socio-economic class and to have a lower BMI. PA overestimators were more likely
      to be in lower socio-economic categories. Self-monitoring and targeted feedback,
      particularly to those in lower socio-economic categories, may improve PA
      perceptions and optimise interventions in T2DM patients. Our findings suggest
      that strategies for enabling realistic assessment of physical activity levels,
      through self-monitoring or feedback, warrant further investigation and may help
      refine and improve physical activity interventions.

PMID- 23883170
TI  - Effects of naringenin and its phase II metabolites on in vitro human macrophage
      gene expression.
AB  - Naringenin, together with its glycosidic forms, is a flavanone abundant in
      grapefruit and orange. It has been detected in human plasma, following citrus
      juice intake, at sub-umolar concentrations, and its main phase II conjugated
      metabolites (naringenin-7-O-glucuronide and narigenin-4'-O-glucuronide) have been
      identified in urine. Recent evidence suggests a potential active anti
      inflammatory role of flavonoids on macrophages, cells actively involved in
      atherogenesis. The aim of this study was to evaluate the effects of naringenin
      and its phase II metabolites on the expression of specific genes in differently
      activated macrophages at concentrations coherent with dietary exposure. Results
      suggest that phase II metabolites, as well as the aglyconic form of naringenin,
      were able to perturb macrophage gene expression in directions that are not always
      consistent with anti-inflammatory effects. Moreover, the effects of metabolites
      were not always consistent with each other and with those of their aglycone,
      underlining the paramount importance of testing physiological forms of
      phytochemicals within in vitro experimental models. In vivo studies are needed to
      further explore these observations and investigate their practical consequences.

PMID- 23883172
TI  - Fabrication of nanoassemblies using flow control.
AB  - Synthetic nanostructures, such as nanoparticles and nanowires, can serve as
      modular building blocks for integrated nanoscale systems. We demonstrate a
      microfluidic approach for positioning, orienting, and assembling such
      nanostructures into nanoassemblies. We use flow control combined with a cross
      linking photoresist to position and immobilize nanostructures in desired
      positions and orientations. Immobilized nanostructures can serve as pivots,
      barriers, and guides for precise placement of subsequent nanostructures. 

PMID- 23883171
TI  - The identification and epidemiology of meticillin-resistant Staphylococcus aureus
      and Clostridium difficile in patient rooms and the ward environment.
AB  - BACKGROUND: Research has indicated that the environment may play an important
      role in the transmission of meticillin-resistant Staphylococcus aureus (MRSA) and
      Clostridium difficile in healthcare facilities. Despite the significance of this
      finding, few data exist from longitudinal studies investigating MRSA and C.
      difficile contamination, concurrently, in both patient rooms and the general ward
      environment. The objectives of this study were to determine the prevalence of
      MRSA and C. difficile contamination in patient rooms and the ward environment and
      identify risk factors associated with a surface being contaminated with these
      pathogens. METHODS: Environmental surfaces in patient rooms and the general
      environment in the medical and surgical wards of a community hospital were
      sampled six times over a 15 week period. Sterile electrostatic cloths were used
      for sampling and information pertaining to the surface sampled was recorded. MRSA
      isolates and C. difficile specimens were obtained from hospitalized
      patients.Enrichment culture was performed and spa typing or ribotyping was
      conducted for MRSA or C. difficile, respectively. Exact logistic regression
      models were constructed to examine risk factors associated with MRSA and C.
      difficile contamination. RESULTS: Sixteen (41%) patient rooms had >= 1 surfaces
      contaminated with MRSA and/or C. difficile. For 218 surfaces investigated, 3.2%
      and 6.4% were contaminated with MRSA or C. difficile, respectively. Regression
      models indicated that surfaces in rooms exposed to a C. difficile patient had
      significantly increased odds of being contaminated with C. difficile, compared to
      surfaces in unexposed patient rooms. Additionally, compared to plastic surfaces,
      cork surfaces had significantly increased odds of being contaminated with C.
      difficile. For 236 samples collected from the ward environment, MRSA and C.
      difficile were recovered from 2.5% and 5.9% of samples, respectively. Overall,
      the majority of MRSA and C. difficile strains were molecularly identified as spa
      type 2/t002 (84.6%, n = 11) and ribotype 078 (50%, n = 14), respectively.
      CONCLUSIONS: In patient rooms and the ward environment, specific materials and
      locations were identified as being contaminated with MRSA or C. difficile. These
      sites should be cleaned and disinfected with increased vigilance to help limit
      the transmission and dissemination of MRSA and C. difficile within the hospital.

PMID- 23883173
TI  - Use of an electronic cognitive aid by a person with Korsakoff syndrome.
AB  - OBJECTIVE: The purpose of the current study was to evaluate the feasibility and
      the effectiveness of the use of a customized personal digital assistant (PDA) to
      support cognitive functioning in a person with Korsakoff syndrome. METHOD: The
      PDA was compared with no external support and the use of a memory watch in a
      single case experimental design. Three main personal goal tasks were defined:
      "arrive at appointments on time", "execute a long-term task successfully", and
      "remember to ask for medication". RESULTS: No significant differences were found
      between the use of the memory watch and the use of the customized PDA. PDA use
      was perceived as feasible and effective and was considered as a more
      comprehensive aid than the memory watch. CONCLUSION: This study shows that a
      person with Korsakoff syndrome is able to use and benefit from a customized PDA.
      Replication of these findings in a larger effectiveness study is necessary.

PMID- 23883174
TI  - Elbow injuries at the London 2012 Summer Olympic Games: demographics and
      pictorial imaging review.
AB  - OBJECTIVE: Elbow injuries in Olympic sports and their imaging findings have not
      been described previously. The main objective of this article is to analyze the
      demographic data on imaging of elbow injuries at the London 2012 Summer Olympic
      Games and to review the spectrum of imaging findings. CONCLUSION: Elbow injuries
      were seen in a wide variety of sports. Judo and weight-lifting contributed nearly
      half of all injuries, with only a surprisingly small number of injuries seen in
      throwing athletes. Knowledge of elbow anatomy coupled with awareness of types of
      elbow injuries and their prevalence in various sports will contribute toward
      improving diagnostic accuracy, handling of workload, and overall provision of
      services at similar major international sporting events in the future.

PMID- 23883175
TI  - Endogenous erythroid colony formation in chronic myeloid leukemia: a recurrent
      finding associated with persistent minimal residual disease under imatinib.
AB  - In vitro endogenous erythroid colony (EEC) formation is a common finding in BCR
      ABL-negative myeloproliferative neoplasms. The aim of the present study was to
      determine the prevalence and the clinical significance of EEC growth in chronic
      myeloid leukemia (CML). Results of clonogeneic progenitor cell assays from 52
      patients with newly diagnosed CML were correlated with disease characteristics at
      presentation and molecular response to imatinib. EECs (median 7 per dish, range 1
      39) were detectable in 16 patients (31%). The proportion of patients with a high
      risk Sokal score was lower in the EEC group (7% vs. 30%, respectively). The
      cumulative incidence of achieving a major molecular response after 2 years of
      imatinib was similar for both groups. However, patients with EECs were less
      likely to achieve a more profound decline of BCR-ABL transcripts. After 6 years
      of imatinib, the cumulative probability [95% CI] of reaching a >=4 log reduction
      of BCR-ABL was 48% [16%; 92%] for patients of the EEC group and 84% [63%; 97%]
      for patients of the No EEC group. The probability [95% CI] of achieving a >4.5
      log reduction of BCR-ABL after 7 years was 13% [2%; 61%] for patients with EECs
      and 52% [30%; 78%] for patients without EECs. In vitro EECs disappeared after
      achievement of a major molecular response in all evaluable patients. The data
      indicate that EEC formation is a recurrent finding in patients with CML which
      deserves further attention as a possible biomarker predicting the degree of
      molecular response to imatinib. 

PMID- 23883176
TI  - Structural modification on copper(I)-pyridylpyrimidine complexes for modulation
      of rotational dynamics, redox properties, and phototriggered isomerization.
AB  - The redox properties of copper pyridylpyrimidine complexes, which undergo linkage
      isomerism based on pyrimidine ring rotation, were compared under different
      coordination environments. A newly synthesized compound, [Cu(Mepypm)(L(Mes))]BF4
      (1.BF4, Mepypm = 4-methyl-2-(2'-pyridyl)pyrimidine, L(Mes) = 2,9-dimesityl-1,10
      phenanthroline) was compared with previously reported complexes of
      [Cu(MepmMepy)(L(Mes))]BF4 (2.BF4, MepmMepy = 4-methyl-2-(6'-methyl-2'
      pyridyl)pyrimidine), Cu(Mepypm)(DPEphos)]BF4 (3.BF4, DPEphos = bis[2
      (diphenylphosphino)phenyl]ether), [Cu(Mepypm)(L(Anth))]BF4 (4.BF4, L(Anth) = 2,9
      bis(9-anthryl)-1,10-phenanthroline), and [Cu(Mepypm)(L(Macro))]BF4 (5.BF4).
      Isomer ratios, isomerization dynamics, redox properties, and photoelectron
      conversion functions varied with the coordination structure. Methyl substituents
      on the 6-position of the pyridine moiety increased steric repulsion and
      contributed to quicker rotation, enhanced photoluminescence, and increased
      photodriven rotational isomerization.

PMID- 23883177
TI  - The Active for Life Year 5 (AFLY5) school-based cluster randomised controlled
      trial protocol: detailed statistical analysis plan.
AB  - BACKGROUND: The Active For Life Year 5 (AFLY5) randomised controlled trial
      protocol was published in this journal in 2011. It provided a summary analysis
      plan. This publication is an update of that protocol and provides a detailed
      analysis plan. UPDATE: This update provides a detailed analysis plan of the
      effectiveness and cost-effectiveness of the AFLY5 intervention. The plan includes
      details of how variables will be quality control checked and the criteria used to
      define derived variables. Details of four key analyses are provided: (a)
      effectiveness analysis 1 (the effect of the AFLY5 intervention on primary and
      secondary outcomes at the end of the school year in which the intervention is
      delivered); (b) mediation analyses (secondary analyses examining the extent to
      which any effects of the intervention are mediated via self-efficacy, parental
      support and knowledge, through which the intervention is theoretically believed
      to act); (c) effectiveness analysis 2 (the effect of the AFLY5 intervention on
      primary and secondary outcomes 12 months after the end of the intervention) and
      (d) cost effectiveness analysis (the cost-effectiveness of the AFLY5
      intervention). The details include how the intention to treat and per-protocol
      analyses were defined and planned sensitivity analyses for dealing with missing
      data. A set of dummy tables are provided in Additional file 1. DISCUSSION: This
      detailed analysis plan was written prior to any analyst having access to any data
      and was approved by the AFLY5 Trial Steering Committee. Its publication will
      ensure that analyses are in accordance with an a priori plan related to the trial
      objectives and not driven by knowledge of the data. TRIAL REGISTRATION:
      ISRCTN50133740.

PMID- 23883178
TI  - Effects of hypo- and hyperthyroid states on herpes simplex virus infectivity in
      the rat.
AB  - OBJECTIVE: Available data from in vitro studies show that thyroid hormones (THs)
      regulate herpes simplex virus (HSV) gene expression and may modulate
      latency/reactivation of the virus. Whether infectivity of the virus is also
      affected by THs is not known. Using animal models (in vivo study) and Vero cell
      culture (in vitro study), we examined the effects of alterations in THs level on
      HSV-1 infectivity. METHODS: Rats were rendered hypo- and hyperthyroid by daily
      addition of methimazole and l-thyroxine into their drinking water, respectively.
      Euthyroid animals served as control. All animals were given a single dose of HSV
      1 (10(7)TCID50, ip) and sacrificed 3 d later. The spleen of the animals was then
      removed and viral particles were recovered from the tissue extract through
      aseptic procedures. Serial dilution of the extracts was prepared and added to
      Vero cell culture. For the in vitro study, the cultures were pretreated with l
      thyroxine and the viral particles were then added. Virus titration was determined
      by Reed-Muench quantal assay. RESULTS: The viral load of spleen in hyperthyroid
      rats was significantly lower (1000-fold) than that of the euthyroid rats.
      Similarly, in vitro presence of supraphysiologic levels of l-thyroxine in the
      culture media of Vero cells decreased virus infectivity. Interestingly,
      hypothyroid animals showed a significant increase (10-fold) in spleen viral load
      as compared to that of their euthyroid counterparts. CONCLUSIONS: These data
      clearly show that the HSV-1 infectivity is affected by THs, and suggest that THs
      or their analogs may have a potential application in prevention and/or treatment
      of viral infections.

PMID- 23883179
TI  - Histopathology of fathead minnow (Pimephales promelas) exposed to hydroxylated
      fullerenes.
AB  - Hydroxylated fullerenes are reported to be very strong antioxidants, acting to
      quench reactive oxygen species, thus having strong potential for important and
      widespread applications in innovative therapies for a variety of disease
      processes. However, their potential for toxicological side effects is still
      largely controversial and unknown. Effects of hydroxylated fullerenes C60(OH)24
      on the fathead minnow (Pimephales promelas) were investigated microscopically
      after a 72-hour (acute) exposure by intraperitoneal injection of 20 ppm of
      hydroxylated fullerenes per gram of body mass. Cumulative, semi-quantitative
      histopathologic evaluation of brain, liver, anterior kidney, posterior kidney,
      skin, coelom, gills and the vestibuloauditory system revealed significant
      differences between control and hydroxylated fullerene-treated fish. Fullerene
      treated fish had much higher cumulative histopathology scores. Histopathologic
      changes included loss of cellularity in the interstitium of the kidney, a primary
      site of haematopoiesis in fish, and loss of intracytoplasmic glycogen in liver.
      In the coelom, variable numbers of leukocytes, including many macrophages and
      fewer heterophils and rodlet cells, were admixed with the nanomaterial. These
      findings raise concern about in vivo administration of hydroxylated fullerenes in
      experimental drugs and procedures in human medicine, and should be investigated
      in more detail.

PMID- 23883180
TI  - A note on protein expression changes in chicken breast muscle in response to time
      in transit before slaughtering.
AB  - Aims of the research were to devise a proteome map of the chicken Pectoralis
      superficialis muscle, as resolved by two-dimensional gel electrophoresis, and to
      characterize protein expression changes in the soluble protein fraction in
      commercial conditions due to age and to time in transit before slaughtering.
      Broilers were reared under commercial conditions until they reached a mean 1.8 kg
      and 36 d, or 2.6 kg and 46 d of age. Transport to the slaughterhouse took 90 or
      220 minutes. Transport-induced stress was assessed from blood metabolites and
      leukocyte cell counts, revealing significant changes in albumin, glucose and
      triglyceride concentrations, in heterophils and leukocyte counts for chickens in
      transit for longer, and in glucose depending mainly on age. The sarcoplasmic
      protein fractions were extracted from a total of 39 breast muscle samples,
      collected 15 min post mortem, for analysis by two-dimensional electrophoresis.
      Image and statistical analyses enabled us to study the qualitative and
      quantitative differences between the samples. Twelve up- or down-regulated
      protein spots were detected (P < 0.05): 8 related to the age effect, 2 to time in
      transit, and 2 to the interaction between the two. Age and time in transit
      influenced the avian proteome regulating the biological processes linked to the
      cellular housekeeping functions, related mainly to metabolism, cell division and
      control of apoptosis. Principal component analysis clustering was used to assess
      differences between birds. Age difference discriminated between the chickens
      analyzed better than time in transit, which seemed to have less general impact on
      the proteome fraction considered here. Isolating and identifying the proteins
      whose expression changes in response to transport duration and age shed some
      light on the biological mechanisms underlying growth and stress-related
      metabolism in chickens. Our results, combined with a further characterization of
      the chicken proteome associated with commercial chicken slaughtering management,
      will hopefully inspire alternative strategies and policies, and action to reduce
      the impact of stress related to time in transit. 

PMID- 23883181
TI  - Mitochondrial 16S rRNA gene-based evolutionary divergence and molecular phylogeny
      of Barilius spp.
AB  - Barilius is an important genus of fish family Cyprinidae, which comprises 22
      species from Indian region. This study aimed to characterize five commonly
      occurring Bariline species, for example, Barilius bakeri. Barilius gatensis.
      Barilius vagra. Barilius bendelisis and Barilius tileo, across the country using
      partial mitochondrial 16 S rRNA gene, to estimate the order of inter- and intra
      species divergence among these species and to establish phylogenetic and
      evolutionary relationships. The average inter-specific divergence was estimated
      as 7.10%. Intra-specific divergence of 0.20% and 0.10% was observed in B.
      gatensis and B. bendelisis that exhibited three and two haplotypes with 0.70 and
      0.60 haplotype diversities, respectively. The NJ and MP phylogenetic trees were
      constructed using 16 S rRNA sequences along with sequences of the other five
      Indian cyprinid species retrieved from NCBI. Phylogenetic trees revealed five
      discrete branches each as a distinct species of the genus and exhibited identical
      phylogenetic relationship with other cyprinids. The study provided adequate
      information to distinguish the five Barilius species and indicated the
      suitability of 16S rRNA gene sequences in genetic divergence and phylogenetic
      studies. 

PMID- 23883182
TI  - The complete mitochondrial genome of the Longnose skate: Raja rhina (Rajiformes,
      Rajidae).
AB  - The complete sequence of mitochondrial DNA of a longnose skate, Raja rhina was
      determined for the first time. It is 16,910 bp in length containing 2 rRNA, 22
      tRNA and 13 protein coding genes with the same gene order and structure as those
      of other Rajidae species. The nucleotide of L-strand is composed of 30.1% A,
      27.2% C, 28.5% T and 14.2% G, showing a slight A + T bias. The G is the least
      used base and markedly lower at the third codon position (5.4%). Twelve of the 13
      protein coding genes use ATG as their start codon while the COX1 starts with GTG.
      As for stop codon, only ND4 shows incomplete stop codon TA. This mitogenome is
      the first report for a species of the genus Raja, and providing a valuable
      resource of genetic information for understanding the phylogenetic relationship
      and the evolution of the genus Raja as well as the family, Rajidae.

PMID- 23883183
TI  - The KUPNetViz: a biological network viewer for multiple -omics datasets in kidney
      diseases.
AB  - BACKGROUND: Constant technological advances have allowed scientists in biology to
      migrate from conventional single-omics to multi-omics experimental approaches,
      challenging bioinformatics to bridge this multi-tiered information. Ongoing
      research in renal biology is no exception. The results of large-scale and/or high
      throughput experiments, presenting a wealth of information on kidney disease are
      scattered across the web. To tackle this problem, we recently presented the
      KUPKB, a multi-omics data repository for renal diseases. RESULTS: In this
      article, we describe KUPNetViz, a biological graph exploration tool allowing the
      exploration of KUPKB data through the visualization of biomolecule interactions.
      KUPNetViz enables the integration of multi-layered experimental data over
      different species, renal locations and renal diseases to protein-protein
      interaction networks and allows association with biological functions,
      biochemical pathways and other functional elements such as miRNAs. KUPNetViz
      focuses on the simplicity of its usage and the clarity of resulting networks by
      reducing and/or automating advanced functionalities present in other biological
      network visualization packages. In addition, it allows the extrapolation of
      biomolecule interactions across different species, leading to the formulations of
      new plausible hypotheses, adequate experiment design and to the suggestion of
      novel biological mechanisms. We demonstrate the value of KUPNetViz by two usage
      examples: the integration of calreticulin as a key player in a larger interaction
      network in renal graft rejection and the novel observation of the strong
      association of interleukin-6 with polycystic kidney disease. CONCLUSIONS: The
      KUPNetViz is an interactive and flexible biological network visualization and
      exploration tool. It provides renal biologists with biological network snapshots
      of the complex integrated data of the KUPKB allowing the formulation of new
      hypotheses in a user friendly manner.

PMID- 23883184
TI  - Autonomous application of quantitative PCR in the deep sea: in situ surveys of
      aerobic methanotrophs using the deep-sea environmental sample processor.
AB  - Recent advances in ocean observing systems and genomic technologies have led to
      the development of the deep-sea environmental sample processor (D-ESP). The D-ESP
      filters particulates from seawater at depths up to 4000 m and applies a variety
      of molecular assays to the particulates, including quantitative PCR (qPCR), to
      identify particular organisms and genes in situ. Preserved samples enable
      laboratory-based validation of in situ results and expanded studies of genomic
      diversity and gene expression. Tests of the D-ESP at a methane-rich mound in the
      Santa Monica Basin centered on detection of 16S rRNA and particulate methane
      monooxygenase (pmoA) genes for two putative aerobic methanotrophs. Comparison of
      in situ qPCR results with laboratory-based assays of preserved samples
      demonstrates the D-ESP generated high-quality qPCR data while operating
      autonomously on the seafloor. Levels of 16S rRNA and pmoA cDNA detected in
      preserved samples are consistent with an active community of aerobic
      methanotrophs near the methane-rich mound. These findings are substantiated at
      low methane sites off Point Conception and in Monterey Bay where target genes are
      at or below detection limits. Successful deployment of the D-ESP is a major step
      toward developing autonomous systems to facilitate a wide range of marine
      microbiological investigations. 

PMID- 23883185
TI  - Reversible aggregation of DNA-decorated gold nanoparticles controlled by
      molecular recognition.
AB  - The programmable assembly of functional nanomaterials has been extensively
      addressed; however, their selective reversible assembly in response to an
      external stimulus has been more difficult to realize. The specificity and
      programmable interactions of DNA have been exploited for the rational self
      assembly of DNA-conjugated nanoparticles, and here we demonstrate the sequence
      controlled disaggregation of DNA-modified gold nanoparticles simply by employing
      two complementary oligonucleotides. Target oligonucleotides with perfectly
      matching sequence enabled dissociation of aggregated nanoparticles, whereas
      oligonucleotides differing by one nucleotide did not cause disassembly of the
      aggregated nanoparticles. Physical aspects of this process were characterized by
      UV-vis absorption, light scattering, and transmission electron microscopy. This
      strategy for programmed disassembly of gold nanoparticles in response to
      biological stimuli demonstrates a fundamentally important concept anticipated to
      be useful for diverse applications involving molecular recognition. 

PMID- 23883186
TI  - Immunogenicity, reactogenicity and safety of an inactivated quadrivalent
      influenza vaccine candidate versus inactivated trivalent influenza vaccine: a
      phase III, randomized trial in adults aged >=18 years.
AB  - BACKGROUND: Two antigenically distinct influenza B lineages have co-circulated
      since the 1980s, yet inactivated trivalent influenza vaccines (TIVs) include
      strains of influenza A/H1N1, A/H3N2, and only one influenza B from either the
      Victoria or Yamagata lineage. This means that exposure to B-lineage viruses
      mismatched to the TIV is frequent, reducing vaccine protection. Formulations
      including both influenza B lineages could improve protection against circulating
      influenza B viruses. We assessed a candidate inactivated quadrivalent influenza
      vaccine (QIV) containing both B lineages versus TIV in adults in stable health.
      METHODS: A total of 4659 adults were randomized 5:5:5:5:3 to receive one dose of
      QIV (one of three lots) or a TIV containing either a B/Victoria or B/Yamagata
      strain. Hemagglutination-inhibition assays were performed pre-vaccination and 21
      days after vaccination. Lot-to-lot consistency of QIV was assessed based on
      geometric mean titers (GMT). For QIV versus TIV, non-inferiority against the
      three shared strains was demonstrated if the 95% confidence interval (CI) upper
      limit for the GMT ratio was <=1.5 and for the seroconversion difference was
      <=10.0%; superiority of QIV versus TIV for the alternate B lineage was
      demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the
      seroconversion difference was > 0%. Reactogenicity and safety profile of each
      vaccine were assessed. Clinicaltrials.gov: NCT01204671. RESULTS: Consistent
      immunogenicity was demonstrated for the three QIV lots. QIV was non-inferior to
      TIV for the shared vaccine strains, and was superior for the added alternate
      lineage B strains. QIV elicited robust immune responses against all four vaccine
      strains; the seroconversion rates were 77.5% (A/H1N1), 71.5% (A/H3N2), 58.1%
      (B/Victoria), and 61.7% (B/Yamagata). The reactogenicity and safety profile of
      QIV was consistent with TIV. CONCLUSIONS: QIV provided superior immunogenicity
      for the additional B strain compared with TIV, without interfering with antibody
      responses to the three shared antigens. The additional antigen did not appear to
      alter the safety profile of QIV compared with TIV. This suggests that the
      candidate QIV is a viable alternative to TIV for use in adults, and could
      potentially improve protection against influenza B. TRIAL REGISTRATION: Clinical
      Trials.gov: NCT01204671/114269.

PMID- 23883187
TI  - Dispersibility and emulsion-stabilizing effect of cellulose nanowhiskers
      esterified by vinyl acetate and vinyl cinnamate.
AB  - The surface of cotton cellulose nanowhiskers (CNW's) was esterified by vinyl
      acetate (VAc) and vinyl cinnamate (VCin), in the presence of potassium carbonate
      as catalyst. Reactions were performed under microwave activation and monitored by
      Fourier transform infrared (FT-IR) spectroscopy. The supramolecular structure of
      CNW's before and after modification was characterized by X-ray diffraction (XRD)
      and atomic force microscopy (AFM). Distinctively from the acetylation treatment,
      an increase in particles dimensions was noted after esterification with VCin,
      which was assigned to pi-pi stacking interactions that may exist between
      cinnamoyl moieties. The dispersibility and emulsion stabilizing effect of
      acylated CNW's was examined in ethyl acetate, toluene, and cyclohexane, three
      organic solvents of medium to low polarity. The acylated nanoparticles could
      never be dispersed in toluene nor cyclohexane, but they formed stable dispersions
      in ethyl acetate while remaining dispersible in water. Stable ethyl acetate-in
      water, toluene-in-water, and cyclohexane-in-water emulsions were successfully
      prepared with CNW's grafted with acetyl moieties, whereas the VCin-treated
      particles could stabilize only the cyclohexane-in-water emulsions. The impact of
      esterification treatment on emulsion stability and droplets size was particularly
      discussed.

PMID- 23883188
TI  - Solvent-switched benzylic methylene functionalization: addition, ring-opening,
      cyclization, and unexpected cleavage of C-O and C-C bonds.
AB  - Intermolecular benzylic methylene functionalization of exo-cyclic enol ethers has
      been achieved using imines as reagents and potassium tert-butoxide as the
      catalyst. Depending on the solvent used, the reaction proceeds by two pathways.
      In THF, an addition/elimination reaction of exo-cyclic enol ethers with imines
      provides dihydroisobenzofuran derivatives in good yield. In DMSO, an
      addition/ring-opening/cyclization cascade reaction occurs with unexpected
      cleavage of C-O and C-C bonds, affording isoquinolin-1(2H)-one products in high
      yield under ambient reaction conditions. 

PMID- 23883189
TI  - Visual analysis in single case experimental design studies: brief review and
      guidelines.
AB  - Visual analysis of graphic displays of data is a cornerstone of studies using a
      single case experimental design (SCED). Data are graphed for each participant
      during a study with trend, level, and stability of data assessed within and
      between conditions. Reliable interpretations of effects of an intervention are
      dependent on researchers' understanding and use of systematic procedures. The
      purpose of this paper is to provide readers with a rationale for visual analysis
      of data when using a SCED, a step-by-step guide for conducting a visual analysis
      of graphed data, as well as to highlight considerations for persons interested in
      using visual analysis to evaluate an intervention, especially the importance of
      collecting reliability data for dependent measures and fidelity of implementation
      of study procedures. 

PMID- 23883190
TI  - Microwave-assisted derivatisation and LC-MS/MS determination of nitrofuran
      metabolites in farm-raised prawns (Penaeus monodon).
AB  - A new microwave-assisted derivatisation and LC-MS/MS method has been developed
      for the analysis of nitrofuran metabolites - 3-amino-5-morpholino-methyl-1,3-oxa
      zolidinone (AMOZ), 3-amino-2-oxazolidinone (AOZ), 1-aminohydantoin (AHD) and
      semicarbazide (SEM) - in farm-raised prawns (Penaeus monodon) from the coastal
      regions of South India. Analysis was carried out by reverse-phase column
      (Phenomenex Luna C18) with gradient elution using mobile phase A (0.02% acetic
      acid in water) and mobile phase B (0.02% acetic acid in acetonitrile), at a flow
      rate of 200 MUl min(-1) and an injection volume of 20 MUl. Microwave-assisted
      derivatisation was achieved in 6 min with good recovery. The results showed that
      the samples collected from Andhra Pradesh and Karnataka contained residues of
      nitrofuran metabolites in the range from 5.0 to 40 ng g(-1). This work emphasises
      the importance of ensuring the safety of seafood and that a new method of
      derivatisation is applicable for the analysis of nitrofuran metabolites in
      seafood.

PMID- 23883193
TI  - Reinvestigation of Np2Se5: a clear divergence from Th2S5 and Th2Se5 in chalcogen
      chalcogen and metal-chalcogen interactions.
AB  - Single crystals of Np2Se5 have been prepared through the reactions of Np and Se
      at 1223 K in an Sb2Se3 flux. The structure of Np2Se5, which has been
      characterized by single-crystal X-ray diffraction methods, crystallizes in the
      tetragonal space group P42/nmc. The crystallographic unit cell includes one
      unique Np and two Se positions. Se(1) atoms form one-dimensional infinite chains
      along the a and b axes with alternating intermediate Se-Se distances of 2.6489
      (8) and 2.7999 (8) A, whereas Se(2) is a discrete Se(2-) anion. Each Np is
      coordinated to 10 Se atoms and every NpSe10 polyhedron shares faces, edges, or
      vertices with 14 other identical metal polyhedra to form a complex three
      dimensional structure. Np LIII-edge X-ray Absorption Near Edge Structure (XANES)
      measurements show a clear shift in edge position to higher energies for Np2Se5
      compared to Np3Se5 (Np(3+)2Np(4+)Se(2-)5). Magnetic susceptibility measurements
      indicate that Np2Se5 undergoes a ferromagnetic-type ordering below 18(1) K. Above
      the transition temperature, Np2Se5 behaves as a paramagnet with an effective
      moment of 1.98(5) MUB/Np, given by a best fit of susceptibilities to a modified
      Curie-Weiss law over the temperature range 50-320 K. 

PMID- 23883192
TI  - Description of Gyrodactylus mediotorus n. sp. (Monogenea: Gyrodactylidae)
      infecting spottail shiner (Notropis hudsonius) from the St. Lawrence River,
      Canada.
AB  - Gyrodactylus mediotorus n. sp. is described from the body, fins, and buccal
      cavity of the spottail shiner, Notropis hudsonius (Cyprinidae) from the St.
      Lawrence River, Quebec, Canada. Gyrodactylus mediotorus n. sp. is the first
      species of Gyrodactylus Nordmann, 1832 described from N. hudsonius and is
      characterized by large hamuli, large medial process of the ventral bar, narrow
      linguiform ventral bar membrane, large anterolateral processes, and marginal
      hooks with long shafts and distinctly shaped sickle. The species that most
      resembles Gyrodactylus mediotorus n. sp. is Gyrodactylus protuberus Rogers and
      Wellborn, 1965 described from the stargazing shiner, Notropis uranoscopus
      Suttkus, 1959. The 2 species can be differentiated based on the larger hamuli
      (68.4 vs. 64) and ventral bar (38.4 vs. 24) of Gyrodactylus mediotorus n. sp. and
      the shape of the marginal hooks which for Gyrodactylus mediotorus n. sp. has a
      slightly larger toe and a point which is not as angled. The morphological
      description is supplemented with 436 sequenced base pairs of the 18S gene
      (including the V4 region) as well as 1,041 sequenced base pairs spanning the
      complete ITS-1, 5.8S, and ITS-2 regions. BLAST (Basic Local Alignment Search
      Tool) searches failed to provide any close matches for either regions of DNA,
      with Gyrodactylus colemanensis infecting Salvelinus fontinalis being the most
      genetically similar for both the 18S (~91%, JF836090) and ITS (~84%, JF836142)
      rDNA regions. Gyrodactylus mediotorus n. sp. has been found infecting spottail
      shiners in the St. Lawrence River in low prevalence and intensities periodically
      over the last 15 yr.

PMID- 23883194
TI  - Sequence-specific inhibition of a nonspecific protease.
AB  - A nonspecific exopeptidase, aminopeptidase N (APN), is inhibited sequence
      specifically by a synthetic host, cucurbit[7]uril (Q7), which binds with high
      affinity and specificity to N-terminal phenylalanine (Phe) and 4
      (aminomethyl)phenylalanine (AMPhe) and prevents their removal from the peptide.
      Liquid chromatography experiments demonstrated that in the presence of excess Q7,
      APN quantitatively converts the pentapeptides Thr-Gly-Ala-X-Met into the
      dipeptides X-Met (X = Phe, AMPhe). The resulting Q7-bound products are completely
      stable to proteolytic digestion for at least 24 h. Structure-activity studies
      revealed a direct correlation between the extent of protection of an N-terminal
      amino acid and its affinity for Q7. Therefore, Q7 provides predictable sequence
      specificity to an otherwise nonspecific protease and enables the production of a
      single peptide product. Conversely, APN uncovers a high-affinity epitope that is
      subsequently bound by Q7, and thus this approach should also facilitate the
      molecular recognition of peptides. 

PMID- 23883195
TI  - Inflammatory processes in complex regional pain syndromes.
AB  - Chronic Regional Pain Syndrome, previously known as reflex sympathetic dystrophy,
      has garnered increased attention in recent years. Many recent studies have
      attempted to better describe the etiology, pathogenesis, and treatment of
      symptoms. Despite recent advances to the fund of medical knowledge, the
      underlying pathophysiology and mechanisms involved in disease progression remain
      unclear. This review will synthesize and present current theories and data
      regarding the role of inflammatory cytokines and other mediators in both the
      central and peripheral nervous systems that contribute to the development and
      progression of CRPS. 

PMID- 23883196
TI  - Current trends and investigative developments in celiac disease.
AB  - Celiac disease has become extensively studied. What could be the cause?
      Increasing the accuracy of diagnostic tests for celiac disease has led to more
      discovered cases. Serological diagnosis of celiac disease has undergone important
      changes in recent years. Application of serological tests has reflected the
      diagnostic performance of tissue transglutaminase antibody and endomysial
      antibody as screening tests for celiac disease but also the progress of new
      serological tests as the antibodies against synthetic deamidated gliadin
      peptides. Serological tests are largely responsible for the recognition that
      celiac disease is not a rare disease. The Consensus in celiac disease from 2008
      conducted under the aegis of the European Society of Pediatric Gastroenterology,
      Hepatology and Nutrition jointly with North American Society of Pediatric
      Gastroenterology, Hepatology and Nutrition which agreed that "Celiac disease is
      an immune-mediated enteropathy that can affect any system or organ and that can
      present itself with a wide range of clinical manifestations of variable severity"
      was confirmed. But increasing prevalence of this disease has led to the need for
      new methods of treatment among patients with celiac disease. Studies on quality
      of life of patients with celiac disease have questioned the gluten-free diet. As
      such new therapies, like TG2 inhibitors, the copolymer P (HEMA-co-SS) and other
      new experimental therapies, have emerged in celiac disease. The new therapies in
      celiac disease are based on new investigations in gluten toxicity screening, like
      K562(S)-cell agglutination, A1 and G12 monoclonal antibodies and proteomics. In
      this paper we want to present the investigative developments in celiac disease.
      We also want to find whether a new treatment in celiac disease is necessary. 

PMID- 23883191
TI  - Perspectives on zebrafish models of hallucinogenic drugs and related psychotropic
      compounds.
AB  - Among different classes of psychotropic drugs, hallucinogenic agents exert one of
      the most prominent effects on human and animal behaviors, markedly altering
      sensory, motor, affective, and cognitive responses. The growing clinical and
      preclinical interest in psychedelic, dissociative, and deliriant hallucinogens
      necessitates novel translational, sensitive, and high-throughput in vivo models
      and screens. Primate and rodent models have been traditionally used to study
      cellular mechanisms and neural circuits of hallucinogenic drugs' action. The
      utility of zebrafish ( Danio rerio ) in neuroscience research is rapidly growing
      due to their high physiological and genetic homology to humans, ease of genetic
      manipulation, robust behaviors, and cost effectiveness. Possessing a fully
      characterized genome, both adult and larval zebrafish are currently widely used
      for in vivo screening of various psychotropic compounds, including hallucinogens
      and related drugs. Recognizing the growing importance of hallucinogens in
      biological psychiatry, here we discuss hallucinogenic-induced phenotypes in
      zebrafish and evaluate their potential as efficient preclinical models of drug
      induced states in humans. 

PMID- 23883197
TI  - Association between a TGFBR2 gene polymorphism (rs2228048, Asn389Asn) and acute
      rejection in Korean kidney transplantation recipients.
AB  - Transforming growth factor-beta (TGF-beta) signaling transduction initiates TGF
      beta activation, resulting in activation of TGF-beta receptor II (TGFBR2). Any
      quantitative and qualitative changes in TGFBR2 are expected to affect the TGF
      beta signaling pathway, which occupies a central position with respect to the
      regulation of cell growth, differentiation, apoptosis, immune reaction,
      angiogenesis and extracellular matrix formation. Recent studies have shown that
      TGF-beta1 gene polymorphisms may confer susceptibility to early acute and chronic
      allograft rejection in kidney transplantation recipients. In this study, we
      assessed whether polymorphisms of the TGFBR2 gene were associated with
      susceptibility to kidney transplantation rejection. A total of 347 renal
      allograft recipients transplanted at three centers in Korea were analyzed. Three
      SNPs (rs764522, rs3087465, rs2228048) of the TGFBR2 gene were genotyped from
      genomic DNA with direct sequencing. Multiple logistic regression models
      (codominant, dominant, recessive, and log-additive) were performed to evaluate
      odds ratios (ORs), 95% confidence intervals (CIs), and p-values. A total of 63
      patients (18%) developed acute rejection (AR). There were no significant
      differences in age, sex, number of HLA mismatches, cause of renal failure, or
      immunosuppressant regimen between the AR and non-AR group. The synonymous SNP
      rs2228048 was significantly associated with AR (p = 0.020 in recessive model, and
      p = 0.036 in log-additive model. The allele frequencies of rs2228048 were
      different between the AR and non-AR group (p = 0.026). These results suggest that
      the synonymous TGFBR2 gene SNP rs2228048 may be associated with the development
      of AR in Korean kidney transplantation recipients. Authors Yeong-Hoon Kim and Tae
      Hee Kim contributed equally to this work and are considered co-first authors. 

PMID- 23883198
TI  - Association of FCRL3 genotypes with susceptibility of Iranian patients to
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a complex disease, the hallmark of which is synovial
      joint inflammation. The substantial contribution from genetic factors in
      susceptibility to RA has been well-defined. The Fc receptor-like3 (FCRL3) gene is
      one of the genes that have recently shown a significant association with RA. To
      determine the possible role of FCRL3-169 C/T and FCRL3-110 A/G gene polymorphisms
      in the development of RA in Iranian patients, 320 RA patients and 302 healthy
      subjects were genotyped by polymerase chain reaction-restriction fragment length
      polymorphism. No significant difference was found in genotype and allele
      frequencies of FCRL3-169 C/T between patients and controls. In contrast, at
      position -110 A/G, the frequency of the AA genotype and A allele was
      significantly decreased in RA patients compared to controls (p = 0.005). After
      Bonferroni correction for multiple testing, no significant correlations between
      FCRL3-169 C/T and -110 A/G polymorphism and laboratory and clinical features of
      the patients was observed. In conclusion, the results of this study showed a
      significant association between FCRL3-110 A/G polymorphism and susceptibility to
      RA. 

PMID- 23883199
TI  - Combined 4-1BB and CD28 costimulation could unleash lymphocytes from
      immunosuppression induced by adipose derived stem cell soluble products.
AB  - Adipose derived stem cells (ASCs) have the potential to differentiate into
      multiple cell lineages with the capacity to suppress immune cells. However, the
      exact mechanism of this suppression is not fully understood. We hypothesized that
      supplying additional lymphocyte costimulation through CD28 and 4-1BB could
      overturn the inhibitory effect of ASCs. To that end, PHA-activated human PBMCs
      were cocultured with ASCs or with conditioned media (CM) prepared from cultured
      ASCs. Growth was analyzed in the presence or absence of anti-CD28 and anti-4-1BB
      antibodies. Results from CFSE dilution analysis with flow cytometry showed that
      significant and dose-dependent suppression of PHA-activated lymphocytes occurred
      in the presence of ASC-like cells or ASC's CM. However, additional costimulation
      of T cells through CD28 and 4-1BB was able to fully recover lymphocyte
      proliferative capacity in the presence of ASC's CM. Neither of the costimulatory
      antibodies could fully recover lymphocyte proliferation following coculture with
      ASCs. Reversal of ASC's immunosuppression through costimulation suggests that
      further investigation of ASC suppression mechanisms is warranted, since many
      clinical applications of ASCs are based on this feature. Moreover, such findings
      have the potential to boost the usefulness of ASCs in the treatment of autoimmune
      disease. 

PMID- 23883200
TI  - Human plasma anti-alpha-galactoside antibody forms immune complex with autologous
      lipoprotein(a).
AB  - Anti-alpha-galactoside antibody (anti-Gal) from human plasma that bound to alpha
      galactoside-bearing guar galactomannan gel and was eluted with specific sugar
      (affinity-purified anti-Gal ; APAG) invariably contained apo(a) and apo B
      subunits in a proportion close to that in plasma lipoprotein(a) [Lp(a)]. Since
      LDL does not contain apo(a), result suggested Lp(a) as a component of APAG. Lp(a)
      in APAG was complexed with anti-Gal since plate-coated anti-apo(a) captured Lp(a)
      along with the antibody. Association of Lp(a) with anti-Gal in APAG was
      considerably lower in presence of anti-Gal-specific sugar, suggesting that Lp(a)
      occupied the sugar-binding site of anti-Gal. Content of Lp(a)-bound anti-Gal in
      APAG, though a minor fraction of total antibody, increased steadily with total
      Lp(a) content of plasma. Further, Lp(a) released from immune complex-rich
      fraction of plasma by anti-Gal- specific sugar was proportional to total plasma
      Lp(a). Anti-Gal titre decreased with increasing Lp(a) concentration among 114
      plasma samples. Results indicate the potential of anti-Gal molecules with its
      binding site partially occupied by Lp(a) molecule(s) to a) use the remaining
      binding site(s) to recognize other macromolecules or cells and b) transport Lp(a)
      across Fc receptor-bearing cells.

PMID- 23883201
TI  - Celiac disease in Tunisian children: a second screening study using a "new
      generation" rapid test.
AB  - This work aims to estimate celiac disease prevalence in school-children in the
      island of Djerba and assess rapid method feasibility for screening. We screened
      2064 schoolchildren by a rapid method to detect IgA anti-tissue transglutaminase
      and IgA deficiency. Children with positive results were tested for IgA anti
      transglutaminase and anti-endomysium by conventional tests. In positive children,
      intestinal biopsy was performed. IgA deficiency suspected by rapid method was
      confirmed by nephelometry. In these cases IgG anti-endomysium was performed.
      Rapid test was positive in 7 children; conventional serology was positive in all
      and 6 of them accepted the biopsy. Total villous atrophy was observed in 5 while
      intestinal mucosa was normal in one. Among children with positive serology, 3 had
      silent form, 1 chronic diarrhea, one growth failure and 2 had borderline growth.
      IgA deficiency was suspected in 13 cases and was confirmed in 11 children tested.
      Prevalence of celiac disease was 0.24-0.34% and that of IgA deficiency 0.5-0.6%.
      This screening study confirms that celiac disease is relatively common in
      schoolchildren in Tunisia. It confirms also that even those with symptoms typical
      for celiac disease escape diagnosis. Rapid test is better accepted by parents and
      children than test requiring a venous blood sample. 

PMID- 23883202
TI  - Measurement of suppressor activity of T CD4+CD25+ T reg cells using
      bromodeoxyuridine incorporation assay.
AB  - The suppressor effect of T regulatory lymphocytes in co-cultures with T effector
      cells obtained by magnetic columns from healthy donors and activated by CD3/CD28
      was measured by a proliferation assay using BrdU incorporation and an ELISA test.
      Tritiated thymidine incorporation was used as a reference since it is the gold
      standard for proliferation assays. Both methods were used simultaneously in the
      same samples in order to compare them. Correlation between them was statistically
      significant (p < 0.001). The purification using magnetic columns was very
      efficient since CD4+CD25+ cells were also FOXP3+ therefore; they were identified
      as suppressor T cells. The use of BrdU incorporation in suppression assays is an
      excellent method that avoids the use of radioactive contaminating materials.

PMID- 23883204
TI  - Medical publishing: new approaches and financial challenges.

PMID- 23883205
TI  - A radiologist's guide to treatment response criteria in oncologic imaging:
      anatomic imaging biomarkers.
AB  - OBJECTIVE: The purpose of this article is to describe the imaging biomarkers of
      treatment response and provide an overview of anatomic imaging biomarkers.
      CONCLUSION: Imaging biomarkers of treatment response have evolved into the
      primary endpoint of response in most phase 2 studies. Anatomic imaging biomarkers
      are applied to depict change in tumor size in response to treatment and are
      currently the most commonly applied method of treatment response evaluation.

PMID- 23883206
TI  - A radiologist's guide to treatment response criteria in oncologic imaging:
      functional, molecular, and disease-specific imaging biomarkers.
AB  - OBJECTIVE: This article reviews the functional, molecular, and disease-specific
      imaging biomarkers of treatment response. CONCLUSION: Substantial progress has
      been made in the evolution of drugs directed at specific targets of the tumor
      lifecycle. These novel agents are predominantly cytostatic, and their efficacy
      may be optimally evaluated by functional, molecular, and disease-specific imaging
      biomarkers.

PMID- 23883207
TI  - JOURNAL CLUB: CT dose optimization for whole-body PET/CT examinations.
AB  - OBJECTIVE. The objective of this study was to optimize CT protocols for whole
      body PET/CT by reducing radiation dose while minimizing effects on image quality.
      MATERIALS AND METHODS. Before protocol optimization, a survey of 140 consecutive
      patients was conducted to establish the baseline dose from a whole-body PET/CT
      examination. Another sample of 100 patients was surveyed to evaluate the
      reduction of radiation dose after implementation of the new protocol. Effective
      dose from the CT component of the examination was estimated using dose-length
      product (DLP) values from reports generated by the scanner and anatomy-specific
      conversion factors. Twenty-six patients who underwent studies before and after
      the optimization were included in an analysis of image quality. All 26 patients
      had maintained the same weight between the examinations and were scanned in the
      same position using a similar technique except for the changes made for CT dose
      optimization. The studies were randomized and blinded for an experienced PET and
      CT reader who graded the imaging quality of anatomic structures. RESULTS. CT
      protocol optimization resulted in a 32% reduction of the mean CT radiation dose:
      The mean effective dose was reduced from 8.1 to 5.5 mSv. The blinded analysis of
      image quality showed no clinically significant degradation of the lower-dose
      studies. The only structures visualized statistically better on the higher-dose
      CT scans were the carotid arteries and the region of the posterior triangle.
      CONCLUSION. The results of this study showed that optimization of CT acquisition
      can effectively reduce radiation dose in a whole-body PET/CT examination without
      significantly sacrificing image quality. 

PMID- 23883208
TI  - Noninfectious inflammatory lung disease: imaging considerations and clues to
      differential diagnosis.
AB  - OBJECTIVE: Noninfectious inflammatory lung diseases represent a spectrum of
      idiopathic and secondary conditions that may involve the airspaces, vasculature,
      or interstitium. The most important clinical and pathologic characteristics are
      reviewed, emphasizing CT findings and potential clues to differential diagnosis.
      CONCLUSION: Noninfectious inflammatory lung diseases translate into various CT
      appearances that are important in making the correct diagnosis.

PMID- 23883209
TI  - Computer-aided segmentation and volumetry of artificial ground-glass nodules at
      chest CT.
AB  - OBJECTIVE: The purpose of this study was to investigate a new software program
      for semiautomatic measurement of the volume and mass of ground-glass nodules
      (GGNs) in a chest phantom and to investigate the influence of CT scanner,
      reconstruction filter, tube voltage, and tube current. MATERIALS AND METHODS: We
      used an anthropomorphic chest phantom with eight artificial GGNs with two
      different CT attenuations and four different volumes. CT scans were obtained with
      four models of CT scanner at 120 kVp and 25 mAs with a soft and a sharp
      reconstruction filter. On the 256-MDCT scanner, the tube current-exposure time
      product and tube voltage settings were varied. GGNs were measured with software
      that automatically segmented the nodules. Absolute percentage error (APE) was
      calculated for volume, mass, and density. Wilcoxon signed rank, Mann-Whitney U,
      and Kruskal-Wallis tests were used for analysis. RESULTS: Volume and mass did not
      differ significantly from the true values. When measurements were expressed as
      APE, the error range was 2-36% for volume and 5-46% for mass, which was
      significantly different from no error. We did not find significant differences in
      APE between CT scanners with filters for lower tube current for volume or lower
      tube voltage for mass. CONCLUSION: Computer-aided segmentation and mass and
      volume measurements of GGNs with the prototype software had promising results in
      this study.

PMID- 23883210
TI  - Tumors and tumorlike conditions of the large airways.
AB  - OBJECTIVE: Large-airway tumors and tumorlike conditions are uncommon, but a
      systematic approach aids in narrowing the differential diagnosis. In this
      article, we describe an approach to dealing with large-airway lesions and discuss
      their imaging characteristics and clinical presentations. CONCLUSION: We have
      found it useful to separate these entities into groups on the basis of the
      distribution pattern (focal vs diffuse) and location (trachea vs bronchi).

PMID- 23883211
TI  - Characterization of 1-to 2-cm liver nodules detected on hcc surveillance
      ultrasound according to the criteria of the American Association for the Study of
      Liver Disease: is quadriphasic CT necessary?
AB  - OBJECTIVE: The purpose of this study was to identify the essential number of
      phases from multiphasic CT for 1- to 2-cm hepatocellular carcinoma (HCC) on
      surveillance ultrasound and to compare the results with the American Association
      for the Study of Liver Disease (AASLD) standard (arterial phase hypervascularity
      and portal venous phase [PVP] or delayed phase hypovascularity). MATERIALS AND
      METHODS: The study included 110 newly detected nodules (1-2 cm; 36 HCC, 74
      benign) in 96 patients detected in an HCC surveillance program. Three
      radiologists prospectively evaluated the attenuation of each nodule relative to
      the liver on each phase of quadriphasic CT. Univariate and multivariate logistic
      regression analyses were used to identify parameters associated with HCC.
      Multiple combinations of phases were compared with the AASLD standard. RESULTS:
      Only arterial phase hypervascularity and delayed phase hypovascularity were
      significantly associated with HCC both on univariate (odds ratio, arterial phase
      7.51 [95% CI, 2.79-20.20]; delayed phase, 2.80 [1.14-6.90]) and multivariate
      analyses (arterial phase, 11.30 [4.30-29.68]; delayed phase, 4.39 [1.20-16.13]).
      The combination of arterial phase and delayed phase yielded the highest
      specificity (99%) and sensitivity (57%). There was no significant difference
      between AASLD standard (sensitivity, 57%; specificity, 98%) versus biphasic
      (arterial phase hypervascularity and delayed phase hypovascularity: sensitivity,
      57%; p = 1 and specificity, 99%; p = 0.32), triphasic (arterial phase
      hypervascularity and unenhanced or PVP hypovascularity: sensitivity, 53%; p =
      0.325 and specificity, 97%; p = 0.32), or quadriphasic combination (arterial
      phase hypervascularity and unenhanced, PVP or delayed phase hypovascularity:
      sensitivity, 57%; specificity, 97%), whereas the sensitivity of biphasic arterial
      phase and PVP was significantly lower (39% vs 57%, p = 0.022). CONCLUSION: For
      diagnosing 1- to 2-cm HCC detected on surveillance ultrasound, arterial phase and
      delayed phase are two essential phases, providing higher sensitivity than the
      combination of arterial phase and PVP, and equal performance with triphasic and
      quadriphasic combinations. The biphasic combination of arterial phase and delayed
      phase may replace quadriphasic CT recommended by AASLD.

PMID- 23883212
TI  - Biologic factors affecting HCC conspicuity in hepatobiliary phase imaging with
      liver-specific contrast agents.
AB  - OBJECTIVE: The purpose of this study was to evaluate factors influencing hepatic
      enhancement and the conspicuity of hepatocellular carcinoma (HCC) on gadobenate
      dimeglu-mine- and gadoxetate disodium-enhanced hepatobiliary phase MR images.
      MATERIALS AND METHODS: Patients with chronic liver disease who underwent liver
      MRI with gadobenate dimeglumine (n = 93) or gadoxetate disodium (n = 92) were
      included in this study. The degree of hepatic enhancement on 1-hour and 3-hour
      delayed phase gadobenate dimeglumine-enhanced and 20-minute delayed phase
      gadoxetate disodium-enhanced hepatobiliary phase images were evaluated with
      quantitative and visual indexes. The conspicuity of 40 HCCs in the gadobenate
      dimeglumine group and 38 HCCs in the gadoxetate disodium group were graded on a 5
      point scale. Correlation between hepatic enhancement indexes and clinical factors
      (age, body weight, serum bilirubin concentration, model for end-stage liver
      disease score, Child-Pugh class, and renal function stage) and association
      between the conspicuity of HCCs and clinical factors, lesion diameter, and
      hepatic enhancement indexes were evaluated. RESULTS: In the gadobenate
      dimeglumine group, the visual index of hepatic enhancement independently
      correlated with Child-Pugh class on both 1- and 3-hour delayed images (p < 0.001)
      and with renal function stage only on 3-hour delayed images (p <= 0.031). In the
      gadoxetate disodium group, both quantitative and visual indexes of hepatic
      enhancement independently correlated with Child-Pugh class (p <= 0.019). The
      conspicuity of HCCs independently correlated with Child-Pugh class and lesion
      diameter on 3-hour delayed gadobenate dimeglumine-enhanced images (p <= 0.031)
      and on gadoxetate disodium-enhanced images (p = 0.033) and significantly
      correlated with the visual index of hepatic enhancement on both gadobenate
      dimeglumine- and gadoxetate disodium-enhanced images (p <= 0.001). CONCLUSION:
      Liver enhancement and conspicuity of HCC are significantly affected by Child-Pugh
      class on both gadobenate dimeglumine- and gadoxetate disodium-enhanced
      hepatobiliary phase MR images.

PMID- 23883213
TI  - Combined hepatocellular and cholangiocarcinoma (biphenotypic) tumors: imaging
      features and diagnostic accuracy of contrast-enhanced CT and MRI.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracy of
      preoperative imaging for diagnosis of combined hepatocellular cholangiocarcinoma
      tumors and to evaluate the clinical and imaging features and demographics of
      patients presenting to our institution with such tumors. MATERIALS AND METHODS:
      From January 2001 to January 2011, 29 patients presented with pathologically
      proven combined hepatocellular cholangiocarcinoma tumors to our institution. A
      retrospective review of the imaging studies, clinical data, and demographic
      information in these patients was conducted. Two radiologists with 6 and 18 years
      of experience reviewed the imaging studies of patients with combined
      hepatocellular cholangiocarcinoma tumors and matched control cases of
      hepatocellular carcinoma (HCC) (n = 15) and cholangiocarcinoma (n = 18). The
      reviewers were blinded to the pathologic diagnosis. Imaging features on contrast
      enhanced MRI and CT with the suggested final diagnosis were recorded. RESULTS:
      The demographics of our patient population were similar to other reported U.S.
      populations, with cirrhosis and hepatitis present in a minority of patients. The
      imaging features of combined hepatocellular cholangiocarcinoma tumors overlapped
      with those of HCC and cholangiocarcinoma. The correct diagnosis of combined
      hepatocellular cholangiocarcinoma tumors was made in a minority of cases by
      either radiologist, with misdiagnosis more often leading to suggestion of
      cholangiocarcinoma than HCC. Sensitivities and specificities for diagnosis of
      combined hepatocellular cholangiocarcinoma tumors ranged from 33% to 34% and 81%
      to 100%, respectively. CONCLUSION: Preoperative diagnosis of combined
      hepatocellular cholangiocarcinoma tumors on the basis of imaging features is
      accurate in the minority of cases. Tumor markers and risk factors may help
      improve accuracy; however, in the absence of classic imaging features and
      supportive information for HCC or cholangiocarcinoma, biopsy should be considered
      for confirmation of diagnosis.

PMID- 23883214
TI  - Usefulness of the tensile gallbladder fundus sign in the diagnosis of early acute
      cholecystitis.
AB  - OBJECTIVE: The purpose of this article is to evaluate the usefulness of the
      tensile gallbladder fundus sign on CT in diagnosing early acute cholecystitis.
      MATERIALS AND METHODS: The tensile gallbladder fundus sign on CT is defined as
      the absence of gallbladder fundus flattening by the anterior abdominal wall due
      to increased gallbladder pressures. Between October 2010 and March 2012, 222
      patients with confirmed diagnoses of acute cholecystitis by surgery or follow-up
      imaging studies underwent CT scans in the emergency department because of right
      upper quadrant pain. Two radiologists retrospectively reviewed all CT images to
      determine the presence of the tensile gallbladder fundus sign and other CT
      findings previously reported to be suggestive of acute cholecystitis. Diagnostic
      performances were calculated and analyzed using pairwise comparisons of receiver
      operating characteristic curves. The kappa statistic was calculated to evaluate
      the interobserver agreement. RESULTS: Using the diagnostic criteria in which
      acute cholecystitis is defined as the presence of three or more classic CT
      findings, the addition of the tensile gallbladder fundus sign increased the area
      under the receiver operating characteristic curve (Az) value from 0.693 to 0.739
      (p = 0.003). In the subgroup of 91 patients with no other CT features suggestive
      of acute cholecystitis, the sensitivity, specificity, and Az value of the tensile
      gallbladder fundus sign for acute cholecystitis were 74.1%, 96.9%, and 0.855,
      respectively. Interobserver agreement was good with the tensile gallbladder
      fundus sign (kappa = 0.721). CONCLUSION: The tensile gallbladder fundus sign may
      be useful for diagnosing acute cholecystitis, especially in the early stage when
      other CT findings are absent.

PMID- 23883215
TI  - Differentiation of papillary renal cell carcinoma subtypes on CT and MRI.
AB  - OBJECTIVE: The objective of our study was to determine the frequency of atypical
      papillary renal cell carcinomas (RCCs) and identify imaging differences between
      type 1 and type 2 papillary RCCs once atypical papillary RCC tumors have been
      excluded. MATERIALS AND METHODS: Eighty-two papillary RCC tumors were classified
      at pathology as type 1, type 2, or atypical. The CT and MRI examinations of these
      tumors were reviewed. Imaging features such as tumor size, margins,
      heterogeneity, and enhancement were assessed and the findings in type 1 and type
      2 tumors were compared. RESULTS: There were 43 type 1 and 13 type 2 tumors.
      Atypical histologic features (i.e., tumors containing both type 1 and type 2
      components, clear cells, or components with atypically high nuclear grade [in
      type 1 tumors] or low nuclear grade [in type 2 tumors]) were seen in 26 tumors.
      On CT, type 2 tumors more commonly had infiltrative margins (p = 0.05) and were
      more likely to have calcifications (p = 0.04) than type 1 tumors, although these
      features were seen in all tumor types. Type 2 tumors were also more heterogeneous
      than type 1 tumors (p = 0.04). On CT, 11 papillary RCCs showed enhancement of
      less than 20 HU, seven of which showed enhancement of less than 10 HU. On MRI,
      all tumors showed enhancement on subtraction images. CONCLUSION: Nearly one third
      of papillary RCCs in our patient population had atypical features at histology.
      On CT and MRI, there are some significant differences in imaging features between
      type 1 and type 2 tumors; however, substantial overlap precludes categorization
      on a per-patient basis. On CT, many papillary RCCs do not enhance, indicating
      that assessment of enhancement alone is insufficient for differentiating
      papillary RCCs from hyperdense cysts.

PMID- 23883216
TI  - Radiologic reporting: the ethical obligation of the interpreting physician to
      provide an accurate report.
AB  - OBJECTIVE: This article focuses on the radiology report and examines how related
      errors can affect patient care even though the radiologist might resist
      disclosing or discussing reporting errors in a patient-centered way. By using
      scenarios involving issues in reporting, we hope to show how various ethical
      theories support the obligation of a radiologist to provide an honest, complete
      report and to ensure that errors are disclosed to patients. CONCLUSION:
      Radiologists should be willing to make corrections when necessary and ethical
      theories and principles are available to guide them in their duty to care for
      their patients. Physicians owe it to their patients, their patients' families,
      and the medical profession to produce an honest and truthful report. Despite
      temptations to deviate from ethically appropriate action, physicians must make
      honesty to their patients and reporting of errors a priority. Few patients expect
      absolute perfection from their physicians, but honesty and truthfulness in
      reporting will advance physician-patient and physician-physician relationships
      and can foster optimal patient care.

PMID- 23883217
TI  - Using a web-based image quality assurance reporting system to improve image
      quality.
AB  - OBJECTIVE: The purpose of this study is to show the impact of a web-based image
      quality assurance reporting system on the rates of three common image quality
      errors at our institution. MATERIALS AND METHODS: A web-based image quality
      assurance reporting system was developed and used beginning in April 2009. Image
      quality endpoints were assessed immediately before deployment (period 1),
      approximately 18 months after deployment of a prototype reporting system (period
      2), and approximately 12 months after deployment of a subsequent upgraded
      department-wide reporting system (period 3). A total of 3067 axillary shoulder
      radiographs were reviewed for correct orientation, 355 shoulder CT scans were
      reviewed for correct reformatting of coronal and sagittal images, and 346 sacral
      MRI scans were reviewed for correct acquisition plane of axial images. Error
      rates for each review period were calculated and compared using the Fisher exact
      test. RESULTS: Error rates of axillary shoulder radiograph orientation were
      35.9%, 7.2%, and 10.0%, respectively, for the three review periods. The decrease
      in error rate between periods 1 and 2 was statistically significant (p < 0.0001).
      Error rates of shoulder CT reformats were 9.8%, 2.7%, and 5.8%, respectively, for
      the three review periods. The decrease in error rate between periods 1 and 2 was
      statistically significant (p = 0.03). Error rates for sacral MRI axial sequences
      were 96.5%, 32.5%, and 3.4%, respectively, for the three review periods. The
      decrease in error rates between periods 1 and 2 and between periods 2 and 3 was
      statistically significant (p < 0.0001). CONCLUSION: A web-based system for
      reporting image quality errors may be effective for improving image quality.

PMID- 23883218
TI  - Application of basic physics principles to clinical neuroradiology:
      differentiating artifacts from true pathology on MRI.
AB  - OBJECTIVE: This article outlines artifactual findings commonly encountered in
      neuroradiologic MRI studies and offers clues to differentiate them from true
      pathology on the basis of their physical properties. Basic MR physics concepts
      are used to shed light on the causes of these artifacts. CONCLUSION: MRI is one
      of the most commonly used techniques in neuroradiology. Unfortunately, MRI is
      prone to image distortion and artifacts that can be difficult to identify. Using
      the provided case illustrations, practical clues, and relevant physical
      applications, radiologists may devise algorithms to troubleshoot these artifacts.

PMID- 23883219
TI  - Traumatic shoulder injuries: a force mechanism analysis-glenohumeral dislocation
      and instability.
AB  - OBJECTIVE: Acute traumatic glenohumeral dislocation is one of the most commonly
      encountered shoulder injuries and can produce a complex combination of associated
      bony and soft-tissue injuries, the full extent of which is often initially
      underappreciated. The objectives of this article are to illustrate the relevant
      anatomy of the shoulder and provide a more intuitive understanding of the complex
      biomechanics of traumatic glenohumeral instability through the use of 3D modeling
      and animation to improve the radiologist's awareness of some of the most common
      injury patterns, and potentially improve the detection of associated injuries.
      Emphasis is placed on the most critical injuries to determine the ultimate
      treatment modality, and imaging recommendations are provided. CONCLUSION:
      Understanding the force mechanisms responsible for traumatic glenohumeral
      dislocation can potentially improve detection of associated secondary injuries,
      which can guide more effective injury classification and ultimately direct more
      appropriate and timely intervention.

PMID- 23883220
TI  - Tram-track appearance of the posterior cruciate ligament (PCL): correlations with
      mucoid degeneration, ligamentous stability, and differentiation from PCL tears.
AB  - OBJECTIVE: The purpose of our study was to describe the MRI findings in the
      posterior cruciate ligament (PCL) analogous to mucoid degeneration in the
      anterior cruciate ligament (ACL); to correlate MRI findings in the PCL with
      ligamentous stability; to differentiate the PCL tram-track appearance from the
      appearance of PCL tears; and to emphasize the coexistence of PCL and ACL mucoid
      degeneration, cruciate ganglia, and meniscal cysts. CONCLUSION: The tram-track
      PCL appearance commonly coexists with ACL mucoid degeneration; ganglia; and, less
      frequently, meniscal cysts. Both PCL tears and MRI findings suggestive of PCL
      mucoid degeneration show ligament thickening and increased PCL signal intensity.
      Tram-track PCLs are usually asymptomatic and typically have no ligamentous
      instability.

PMID- 23883221
TI  - Evaluation of a limited three-slice head CT protocol for monitoring patients with
      ventriculoperitoneal shunts.
AB  - OBJECTIVE: Patients with a ventriculoperitoneal shunt for the management of
      hydrocephalus often undergo multiple head CT examinations for assessment of shunt
      malfunction. The purpose of this study was to evaluate whether a limited three
      slice CT protocol would consistently provide adequate information for the
      diagnosis of shunt malfunction with a decrease in effective dose. MATERIALS AND
      METHODS: The study group included 231 unenhanced head CT examinations performed
      on 128 patients with shunts for hydrocephalus. The original contiguous CT images
      were reviewed retrospectively. A theoretic limited three-slice study was then
      created from the original complete CT study and separately reviewed. This limited
      three-slice study was created by using the lateral topographic image to select
      three axial locations as follows: midpoint between foramen magnum and vertex, top
      of the mastoid air cells, and orbital roof. The limited study was graded for
      parameters of image adequacy with the original full protocol study as the
      reference standard. RESULTS: Twenty-four of the 231 (10.4%) full studies had
      findings consistent with shunt failure; all 231 studies would have been correctly
      categorized with the limited three-slice protocol. The sensitivity of three-slice
      CT for identifying the ventricular system was 91.6% and for identifying the
      catheter tip, 93.5%. Limited-slice CT examination would have resulted in greater
      than 90% mean dose reduction in both adult and pediatric populations. CONCLUSION:
      Unenhanced head CT with a limited-slice protocol provides adequate diagnostic
      information for the diagnosis of shunt malfunction with a greater than 90%
      reduction in effective dose.

PMID- 23883222
TI  - Mastoid findings secondary to posterior fossa dural venous sinus thrombosis.
AB  - OBJECTIVE: In the setting of posterior fossa dural venous sinus thrombosis,
      mastoid findings can potentially be mistaken as the cause rather than a secondary
      effect. Obstruction of the mastoid venous drainage can lead to transudation of
      fluid into the mastoid air cells. We hypothesize that a continuum of the mastoid
      manifestations secondary to dural venous sinus thrombosis can be seen on MRI and
      that the difference in venous drainage between the mastoid and middle ears can
      assist with this important imaging differential. MATERIALS AND METHODS: A
      retrospective review of acute dural venous sinus thrombosis cases and their
      follow-up imaging were graded as follows: no involvement; grade 1 mucosal
      congestion; grade 2, film of fluid; or grade 3, complete opacification. Presence
      of middle ear fluid was also documented. RESULTS: Of 22 posterior fossa dural
      venous sinus thrombosis cases without clinical infectious mastoiditis, 19 had
      mastoid findings: eight with grade 1, eight with grade 2, and three with grade 3.
      Middle ear fluid was seen in only one case. There was a statistically significant
      association between posterior fossa dural venous sinus thrombosis and mastoid
      findings (chisquare test (n = 22), p < 0.04). Fifteen of 18 cases with follow-up
      MRI examinations showed lessening of the mastoid findings with resolving dural
      venous sinus thrombosis. CONCLUSION: Acute posterior fossa dural venous sinus
      thrombosis may present with a spectrum of mastoid findings that should not be
      misdiagnosed as the cause of the thrombosis. This study illustrates that in the
      absence of clinical findings of mastoiditis, mastoid fluid with a clear middle
      ear argues that the mastoid changes are the effect of the dural venous sinus
      thrombosis rather than the cause.

PMID- 23883223
TI  - Association of MRI findings and visual outcome in idiopathic intracranial
      hypertension.
AB  - OBJECTIVE: Patients with idiopathic intracranial hypertension (IIH) have elevated
      intracranial pressure (ICP) without an identifiable cause. The clinical course is
      variable, resulting in irreversible vision loss in some and a benign course in
      others. Although MRI findings have been described in IIH, their association with
      visual outcome has not been evaluated to date. MATERIALS AND METHODS: Forty-six
      patients with IIH underwent funduscopic evaluation, visual field testing, lumbar
      puncture with opening pressure (OP) measurement, and MRI. Patients were
      stratified into the following groups by visual outcome: group 1, no vision loss
      (n = 28); group 2, some vision loss (n = 10); and group 3, severe vision loss (n
      = 8). MRI findings in the orbits, pituitary gland, and optic canals and the
      frequency of skull base cephaloceles and of transverse sinus (TS) stenosis were
      assessed by a reviewer blinded to the patients' visual outcome. Demographic,
      clinical, and MRI findings were evaluated for association with visual outcome.
      RESULTS: Patients in group 3 (worst visual outcome) were significantly younger (p
      = 0.03) and had higher OP (p = 0.04) than patients in the other groups. There
      were no significant differences in sex, race, or body mass index. Despite worse
      visual outcomes and sometimes fulminant vision loss, there were no differences in
      the frequency of orbital MRI findings or TS stenosis, optic canal diameter, and
      pituitary appearance among the three groups. Group 3 had significantly lower
      cephalocele frequency than the other groups (p = 0.04). CONCLUSION: Although MRI
      findings may suggest elevated ICP and the diagnosis of IIH, they are not
      predictive of visual outcome in patients with IIH.

PMID- 23883224
TI  - Periodic MRI lung volume assessment in fetuses with congenital diaphragmatic
      hernia: prediction of survival, need for ECMO, and development of chronic lung
      disease.
AB  - OBJECTIVE: The purpose of the study was to investigate the ability to predict
      survival, need for extracorporeal membrane oxygenation (ECMO), and incidence of
      chronic lung disease in patients with congenital diaphragmatic hernia in the
      context of a classification into three different times of gestation (< 28, 28-32,
      and > 32 weeks) by assessing the ratio between observed and expected MRI fetal
      lung volume. MATERIALS AND METHODS: The data analysis included 226 fetuses with
      congenital diaphragmatic hernia. MRI was performed at different times of
      gestation with a T2-weighted HASTE sequence. Receiver operating characteristic
      curve analysis was performed to investigate the prognostic value of assessment of
      the ratio between observed and expected MRI fetal lung volumes at different
      stages of fetal growth. RESULTS: For all reviewed times of gestation, the ratio
      between observed and expected MRI fetal lung volumes had almost equivalent
      statistically significant differences for neonatal survival (p <= 0.0029), need
      for ECMO therapy (p <= 0.0195), and development of chronic lung disease (p <=
      0.0064). Results with high prognostic accuracy for early and for medium and late
      times in gestation also were obtained. Receiver operating characteristic analysis
      showed the highest area under the curve (>= 0.819) for neonatal survival.
      CONCLUSION: In patients with congenital diaphragmatic hernia, the relation
      between observed and expected MRI fetal lung volume is a valuable prognostic
      parameter for predicting neonatal mortality, morbidity represented by the
      development of chronic lung disease, and the need for ECMO therapy in early
      gestation (< 28 weeks) as well as later gestation with no statistically
      significant differences.

PMID- 23883225
TI  - MRI of suspected lower extremity musculoskeletal infection in the pediatric
      patient: how useful is bilateral imaging?
AB  - OBJECTIVE: The purpose of this study was to determine the frequency of bilateral
      abnormalities in children with suspected lower extremity musculoskeletal
      infection and the impact of detection of contralateral abnormalities by MRI on
      patient management. MATERIALS AND METHODS: A retrospective review of 165
      consecutive bilateral lower extremity MRI examinations performed for suspected
      musculoskeletal infection in pediatric patients (64% boys and 36% girls; mean
      age, 7.5 years; age range, 0-18 years) in 2010 at a children's hospital was
      performed. Imaging findings were compared with the final clinical diagnosis and
      management. RESULTS: The MRI examination was normal in 2% (4/165). Osteomyelitis
      was diagnosed in 33% (54/165) of the MRI examinations; among these examinations
      20% (11/54) had both ipsilateral septic arthritis and osteomyelitis, 2% (1/54)
      had bilateral osteomyelitis, and 67% (111/165) of the examinations were negative
      for osteomyelitis. Bilateral abnormalities were detected in 20% (22/111) of
      patients without osteomyelitis, with 18% (4/22) presenting with bilateral signs
      or symptoms. Abnormalities in the contralateral extremity included myositis (18%,
      4/22), stress reaction (18%, 4/22), subcutaneous edema (18%, 4/22), leukemia
      (14%, 3/22), reactive joint effusion (14%, 3/22), Baker cyst (5%, 1/22), and
      osteonecrosis (5%, 1/22). Identification of clinically unsuspected abnormalities
      of the contralateral extremity by MRI was not associated with alterations in
      medical or surgical management in children with or without osteomyelitis.
      CONCLUSION: Clinically unsuspected abnormalities of the asymptomatic
      contralateral lower extremity are common in children referred for MRI of
      suspected musculoskeletal infection. However, detection of these abnormalities is
      not associated with alterations in patient management.

PMID- 23883226
TI  - Imaging-guided biopsy of (18)F-FDG-avid extrapulmonary lesions: do lesion
      location and morphologic features on CT affect the positive predictive value for
      malignancy?
AB  - OBJECTIVE: The purpose of our study was to analyze the effect of lesion location
      and morphologic appearance on CT on the positive predictive value (PPV) for
      malignancy of all extrapulmonary lesions that were (18)F-FDG avid on PET/CT and
      that were biopsied under imaging guidance. MATERIALS AND METHODS: Between January
      2004 and December 2010, 227 patients underwent imaging-guided biopsy of 231 PET
      positive extrapulmonary lesions with diagnostic pathologic results. The PET PPV
      for malignancy was retrospectively calculated and stratified according to lesion
      location and morphologic appearance. RESULTS: The overall PET PPV for malignancy
      was 72%. Inflammatory processes accounted for the majority of benign biopsy
      results. Lesion location significantly affected the PPV (p < 0.001). Bone (96%)
      and liver (90%) lesions had significantly higher PPVs for malignancy compared
      with other locations, whereas lymph nodes (60%) had a significantly lower PPV for
      malignancy. Lesions that were morphologically suspicious and morphologically
      benign according to CT findings alone were associated with PPVs of 74% and 57%,
      respectively (p = 0.05). FDG-avid subcentimeter lymph nodes (n = 8) had a PPV for
      malignancy of 38%. CONCLUSION: Over half of PET-avid morphologically benign
      appearing lesions and one third of PET-avid subcentimeter lymph nodes were found
      to be malignant at biopsy, suggesting that benign morphologic appearance alone
      should not preclude further workup of a PET-positive lesion. Biopsies of FDG-avid
      lesions in liver and bone yielded high rates of true malignancy, whereas biopsies
      of lymph nodes yielded a lower rate of malignancy compared with other lesion
      locations.

PMID- 23883227
TI  - Frequency of carcinoma at secondary imaging-guided percutaneous breast biopsy
      performed after a high-risk pathologic result at primary biopsy.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency of carcinoma
      identified with secondary presurgical imaging-guided percutaneous biopsy for
      patients with high-risk pathologic findings at primary percutaneous biopsy.
      MATERIALS AND METHODS: A retrospective computerized search of our breast imaging
      database from January 1, 2005, to October 1, 2010, was conducted to identify the
      cases of patients with high-risk pathologic findings at primary biopsy who
      underwent at least one secondary biopsy within 9 months and underwent surgical
      excision. Lesion type, location, biopsy guidance, device, number of samples, and
      histopathologic findings were recorded. The pathologic findings at surgical
      excision were compared with the percutaneous biopsy results. RESULTS: One hundred
      twenty-three patients underwent 158 secondary biopsies. On average, 1.3
      additional biopsies were performed per patient. Among the 158 secondary biopsies,
      105 (66.4%) had benign, 48 (30.4%) had high-risk, and five (3.2%) had malignant
      histopathologic findings. No malignant tumors were identified at secondary
      percutaneous biopsies in cases in which the same lesion type was biopsied in the
      same quadrant. Use of secondary percutaneous biopsy led to detection of nine
      malignant tumors in 7.3% of patients-with percutaneous biopsy in four (3.2%)
      patients and at surgical excision in five (4.1%) patients. CONCLUSION: After
      initial imaging-guided percutaneous biopsy reveals high-risk pathologic findings,
      identification of additional high-risk lesions at secondary percutaneous biopsy
      is common, and detection of malignancy is relatively infrequent. However, because
      the secondarily identified high-risk lesions are sometimes upstaged to cancer at
      surgical excision, additional imaging-directed biopsy has potential benefit for
      patients with known highrisk lesions and multiple synchronous findings.

PMID- 23883228
TI  - Malignant invasion of the nipple-areolar complex of the breast: usefulness of
      breast MRI.
AB  - OBJECTIVE: The objective of our study is to assess the usefulness of breast MRI
      for the evaluation of malignant invasion of the nipple-areolar complex. MATERIALS
      AND METHODS: Breast MRI findings of 51 pathologically proven breast cancer
      lesions, which were within 2 cm distance from the nipple-areolar complex on
      sonography, were reviewed retrospectively. Breast MRI examinations were
      retrospectively reviewed for nipple inversion or retraction, periareolar skin
      thickening, nipple-areolar complex enhancement, relationship to the subareolar
      mass, malignant mass pattern, thickness of nipple-areolar complex enhancement,
      tumor-nipple distance, and tumor size and were correlated with the pathologic
      findings. The characteristic findings of Paget disease were reviewed. Mammography
      was reviewed independently without the knowledge of MRI findings. RESULTS: A
      statistically significant correlation was found between nipple-areolar complex
      enhancement and malignant invasion of the nipple-areolar complex, with a
      sensitivity of 93.8% and a specificity of 85.7%. On the basis of univariate and
      multivariate analyses, nipple-areolar complex enhancement and thickness of the
      nipple-areolar complex enhancement correlated significantly with pathologic
      invasion of the nipple-areolar complex (p < 0.001). Paget disease was confirmed
      in 63% of the lesions, and all cases of Paget disease revealed nipple-areolar
      complex enhancement on MRI. No statistically significant correlations were
      observed between the mammographic findings and malignant invasion of the nipple
      areolar complex (p > 0.05). CONCLUSION: MRI is a useful method for the evaluation
      of malignant invasion of the nipple-areolar complex. Nipple-areolar complex
      enhancement with thickening could suggest the possibility of nipple involvement.

PMID- 23883229
TI  - Does formal instruction about the BI-RADS ultrasound lexicon result in improved
      appropriate use of the lexicon?
AB  - OBJECTIVE: The purpose of this article is to determine whether formal instruction
      regarding the BI-RADS ultrasound lexicon results in improved appropriate use of
      the lexicon. MATERIALS AND METHODS: Ninety test questions depicting the features
      outlined by the 2003 BI-RADS lexicon were identified in our PACS. Informed
      consent was obtained from 34 radiology residents. The participants took the
      preinstruction test and then had 1 hour of formal instruction regarding the BI
      RADS ultrasound lexicon, which included images depicting the different
      sonographic features and final assessment (including subcategories 4a, 4b, and
      4c). The participants then completed the postinstruction test, which examined the
      same content. Test scores were calculated for both the pre- and postinstruction
      tests and then were compared by a linear mixed model and Wilcoxon signed rank
      tests. RESULTS: The participants' postinstruction test scores showed significant
      improvement in the overall use of the BI-RADS ultrasound lexicon (p < 0.0001).
      There was also significant improvement in the following specific areas: final
      assessment (p = 0.0005), margin (p = 0.0003), orientation (p = 0.0104), and
      lesion boundary (p = 0.0050). The categories for which test scores did not show
      significant improvement were echo pattern (p = 0.07), posterior acoustic features
      (p = 0.50), shape (p = 0.98), and subset of the final assessment (p = 0.24).
      CONCLUSION: Formal instruction regarding the BI-RADS ultrasound lexicon results
      in improved lesion characterization and final assessment.

PMID- 23883231
TI  - Focal large airway anomalies and abnormalities in pediatric patients.

PMID- 23883232
TI  - Nonneoplastic diseases of the small intestine: differential diagnosis and Crohn
      disease.

PMID- 23883233
TI  - Imaging tumor angiogenesis: the road to clinical utility.
AB  - OBJECTIVE: Tumor growth and progression require the formation of new blood
      vessels from preexisting vasculature, a process called angiogenesis. The ability
      to noninvasively visualize angiogenesis may provide new opportunities to more
      appropriately select patients for antiangiogenesis treatment and to monitor
      treatment efficacy. CONCLUSION: The superior molecular sensitivity of PET and the
      lack of radiation from MRI and contrast-enhanced ultrasound put these techniques
      at the forefront of clinical translation.

PMID- 23883234
TI  - The role of PET/CT in the management of cervical cancer.
AB  - OBJECTIVE. Cervical cancer is the second most common malignancy in women
      worldwide and the third most common cause of cancer mortality in the United
      States. The aim of this article is to describe cervical cancer and outline the
      value of (18)F-FDG PET/CT in the management of cervical malignancy. CONCLUSION.
      The value of PET/CT has been found in staging and treatment strategy for cervical
      cancer. FDG PET/CT facilitates decision-making and radiation treatment planning
      and provides important information about treatment response, disease recurrence,
      and long-term survival. 

PMID- 23883235
TI  - Reporter gene imaging.
AB  - OBJECTIVE: The purposes of this article are to summarize the basic concept and
      the strategies of reporter imaging; introduce reporter genes frequently used in
      optical imaging, nuclear medicine, and MRI for in vivo application; and show
      typical examples of reporter gene imaging. CONCLUSION: In molecular biology, many
      reporter genes have been developed for monitoring cellular processes. Development
      of controlled gene delivery systems promotes construction of various types of
      reporter genes for monitoring the level of a gene expression, promoter activity,
      and protein-protein interaction. When an imaging reporter gene is placed under
      the control of a promoter, the amount of reporter protein can be dynamically
      visualized in vivo. Instrumental advances in molecular imaging have increased the
      sensitivity and resolution of in vivo reporter imaging. Though several types of
      reporters and multimodal imaging instruments are currently available, more
      efficient multimodal reporter gene systems and detectors compatible with several
      imaging modalities are needed.

PMID- 23883236
TI  - FDG PET/CT in the management of primary pleural tumors and pleural metastases.
AB  - OBJECTIVE. FDG PET/CT is emerging as an important modality in the evaluation of
      pleural tumors. PET/CT has an established role in the diagnosis and staging and
      shows promise in therapy planning, therapy response assessment, and providing
      prognostic information in patients with malignant pleural mesothelioma. This
      modality has distinct advantages in characterizing other primary pleural tumors
      and pleural metastases. CONCLUSION. FDG PET/CT is a useful imaging modality in
      the management of patients with primary pleural tumors and pleural metastases. 

PMID- 23883237
TI  - Stenosis quantification of coronary arteries in coronary vessel phantoms with
      second-generation dual-source CT: influence of measurement parameters and
      limitations.
AB  - OBJECTIVE: The purpose of this study was to use second-generation dual-source CT
      to assess the influence of size, degree of stenosis, luminal contrast
      attenuation, and plaque geometry on stenosis quantification in a coronary artery
      phantom. MATERIALS AND METHODS: Six vessel phantoms with three outer diameters
      (2, 3, and 4 mm), each containing three radiolucent plaques (72.2 HU) that
      simulated eccentric and concentric 43.8%, 75%, and 93.8% stenoses were made with
      a 3D printer system. These phantoms were filled with an iodine-saline solution
      mixture at luminal attenuations of 150, 200, 250, 300, and 350 HU and were
      attached to a cardiac motion simulator. Dual-source CT was performed with a
      standardized ECG-gated protocol (120 kV, 360 mAs per rotation) at a simulated
      heart rate of 70 beats/min. Two independent readers quantified the degree of
      stenosis using area-based measurements. RESULTS: All measurements were highly
      reproducible (intraclass correlation, >= 0.791; p < 0.001). The mean measured
      degree of stenosis for a phantom with a 3-mm outer diameter at 250-HU luminal
      attenuation was 49.0% +/- 10.0% for 43.8% stenosis, 71.7% +/- 9.6% for 75.0%
      stenosis, and 85.4% +/- 5.9% for 93.8% stenosis. With decreasing phantom size,
      measurement error increased for all degrees of stenosis. The absolute error
      increased for measurements at a low luminal attenuation of 150 HU (p < 0.001) and
      for low-grade stenoses compared with medium-and high-grade stenoses (p < 0.001).
      CONCLUSION: The results are an overview of factors that influence stenosis
      quantification in simulated coronary arteries. Dual-source CT is highly
      reproducible and accurate for quantification of low-density stenosis in vessels
      with a diameter of 3 mm and attenuation of at least 200 HU for different degrees
      of stenosis and plaque geometry.

PMID- 23883238
TI  - Sinogram-affirmed iterative reconstruction of low-dose chest CT: effect on image
      quality and radiation dose.
AB  - OBJECTIVE. The purpose of this study is to compare sinogram-affirmed iterative
      reconstruction (SAFIRE) and filtered back projection (FBP) reconstruction of
      chest CT acquired with 65% radiation dose reduction. MATERIALS AND METHODS. In
      this prospective study involving 24 patients (11 women and 13 men; mean [+/- SD]
      age, 66 +/- 10 years), two scan series were acquired using 100 and 40 Quality
      Reference mAs over a 10-cm scan length in the chest with a 128-MDCT scanner. The
      40 Quality Reference mAs CT projection data were reconstructed with FBP and four
      settings of SAFIRE (S1, S2, S3, and S4). Six image datasets (FBP with 100 and 40
      Quality Reference mAs, and S1, S2, S3, S4 with 40 Quality Reference mAs) were
      displayed on a DICOM-compliant 55-inch 2-megapixel monitor for blinded evaluation
      by two thoracic radiologists for number and location of lesions, lesion size,
      lesion margins, visibility of small structures and fissures, and diagnostic
      confidence. Objective noise and CT values were measured in thoracic aorta for
      each image series, and the noise power spectrum was assessed. Data were analyzed
      with analysis of variance and Wilcoxon signed rank tests. RESULTS. All 186
      lesions were seen on 40 Quality Reference mAs SAFIRE images. Diagnostic
      confidence on SAFIRE images was higher than that for FBP images. Except for the
      minor blotchy appearance on SAFIRE settings S3 and S4, no significant artifacts
      were noted. Objective noise with 40 Quality Reference mAs S1 images (21.1 +/- 6.1
      SD of HU) was significantly lower than that for 40 Quality Reference mAs FBP
      images (28.5 +/- 8.1 SD of HU) (p < 0.001). Noise power spectra were identical
      for SAFIRE and FBP with progressive noise reduction with higher iteration SAFIRE
      settings. CONCLUSION. Iterative reconstruction (SAFIRE) allows reducing the
      radiation exposure by approximately 65% without losing diagnostic information in
      chest CT. 

PMID- 23883239
TI  - Diagnostic performance of cardiac stress perfusion MRI in the detection of
      coronary artery disease using fractional flow reserve as the reference standard:
      a meta-analysis.
AB  - OBJECTIVE. This is an analysis of pooled studies for the determination of the
      test characteristics of stress perfusion cardiac MRI in the diagnosis of flow
      limiting obstructive coronary artery disease (CAD) using fractional flow reserve
      (FFR) at catheter coronary angiography as the reference standard. MATERIALS AND
      METHODS. Traditionally, planimetric measurement of coronary stenosis at catheter
      coronary angiography has been considered the reference standard and has been used
      to verify the diagnostic characteristics of gatekeeper tests. FFR is a
      physiologic measure of flow limitation and is considered a more authentic
      reference standard in the diagnosis of CAD. The emergence of a new reference
      standard questions the true diagnostic accuracy of gatekeeper tests. A systematic
      literature review was performed for qualifying studies. The DerSimonian-Laird
      random effects model and a random-effects symmetric summary receiver operating
      characteristic curve analysis were performed. RESULTS. Twelve studies (761
      patients) met the inclusion criteria. Four hundred six stenotic coronary arteries
      had FFR less than 0.75. Perfusion stress MRI has a sensitivity of 89.1% (95% CI,
      84-93%) and specificity of 84.9% (95% CI, 76.6-91.1%) on a patient basis and a
      sensitivity of 87.7% (95% CI, 84.4-90.6%) and specificity of 88.6% (95% CI, 86.7
      90.4%) on a coronary territory basis. CONCLUSION. Stress perfusion MRI remains an
      accurate test for the detection of flow-limiting stenosis when adjudicated by a
      physiologic reference standard. 

PMID- 23883240
TI  - Extent of arterial tumor enhancement measured with preoperative MDCT gastrography
      is a prognostic factor in advanced gastric cancer after curative resection.
AB  - OBJECTIVE: The objective of this study was to investigate the correlation between
      pathologic findings and arterial tumor enhancement at MDCT gastrography of
      patients with a prognosis of advanced gastric cancer after curative resection.
      MATERIALS AND METHODS: The cases of 41 patients with advanced gastric cancer (23
      men, 18 women; age range, 35-92 years; median, 60 years) who underwent MDCT
      gastrography and optical endoscopy before surgery were retrospectively evaluated.
      Two radiologists reviewed virtual endoscopic and multiplanar reconstruction
      images to measure arterial phase CT values of the inner tumor margin and healthy
      gastric wall. They used consensus regions of interest on a cross-sectional image
      of the largest tumor diameter and then calculated tumor-to-normal wall
      enhancement ratio (TNR). Advanced gastric cancers were divided into high- and low
      TNR groups with mean TNR as the cutoff. The correlations between groups and
      pathologic factors, patient survival, and mode of recurrence were studied.
      RESULTS: Multivariate logistic regression analysis showed that the arterial tumor
      enhancement ratio correlated with both microvessel density and lymphatic vessel
      invasion. The survival rate after curative resection was worse for the high-TNR
      group than for the low-TNR group. The rate of lymphatic and hematogenous
      recurrences was also higher in the high-TNR group. Multivariate survival analysis
      revealed that TNR was an independent prognostic factor. CONCLUSION: The extent of
      arterial tumor enhancement correlated with tumor angiogenesis and lymphatic
      vessel invasion and was a useful prognostic indicator after curative resection in
      patients with advanced gastric cancer.

PMID- 23883241
TI  - Imaging evaluation of laparoscopic greater curvature plication: preliminary
      observations.
AB  - OBJECTIVE: The purpose of this article is to assess normal imaging findings and
      complications after laparoscopic greater curvature plication on luminal upper
      gastrointestinal studies and CT. MATERIALS AND METHODS: This was a retrospective
      chart review of 24 adults who underwent laparoscopic greater curvature plication
      between 2008 and 2011. Seventeen patients (70.8%) underwent postoperative luminal
      upper gastrointestinal studies, and four (16.7%) underwent postoperative CT.
      Normal imaging features and complications were recorded. The percentage of
      intraluminal gastric diameter occupied by the plicated segment and the percentage
      of greater curvature involved on postoperative upper gastrointestinal luminal
      studies were determined. RESULTS: A multilobular intraluminal filling defect
      reflecting the surgical plication occupied the proximal third of the greater
      curvature in 16 of 17 patients (94%), extending to the mid portion in 10 of 17
      patients (59%) and to the distal third in one of 17 patients (6%). There was
      luminal narrowing of 50-75% in 14 of 17 patients (82%) and narrowing of 25-50% in
      two patients (12%). In 14 of 17 patients (82%), the plication involved 50-75% of
      the greater curvature length and 25-50% in the remaining three patients (18%). In
      four patients who underwent CT, a central low-attenuation stripe accompanied the
      plication. Five of 24 patients (21%) had complications, including extraluminal
      gastric leak (n = 1), gastric outlet obstruction (n = 2), and plication suture
      failure (n = 2). CONCLUSION: Laparoscopic greater curvature plication is seen as
      multilobular filling defects most commonly along the proximal greater curvature
      with 50-75% narrowing of the gastric lumen. A linear low-attenuation stripe
      accompanies the filling defect on CT.

PMID- 23883242
TI  - Sonography of small bowel perforation.
AB  - OBJECTIVE: This article aims to illustrate the spectrum of sonographic findings
      in perforation of the small bowel due to a variety of causes and discusses the
      potential role of sonography in the diagnosis. CONCLUSION: Although sonography is
      not the first-line investigation of choice in suspected small intestinal
      perforation, an understanding of the characteristic appearances seen during
      general abdominal sonography may aid the radiologist in the early diagnosis.
      Recognition of small bowel perforation on general abdominal sonography will
      shorten the time to diagnosis and ultimate surgical management.

PMID- 23883243
TI  - Cystic renal cell carcinomas: do they grow, metastasize, or recur?
AB  - OBJECTIVE: The purpose of this study is to evaluate the interval growth, tumor
      recurrence, and metastatic disease occurrence of cystic renal cell carcinoma
      (RCC). MATERIALS AND METHODS: Pre-and posttreatment imaging of 47 histologically
      proven cystic RCCs, with at least 6 months of pretreatment imaging monitoring or
      at least 2 years of posttreatment imaging follow-up, or both, was retrospectively
      reviewed. Tumor morphologic features, preoperative growth, histologic typing and
      grading, and the incidence of tumor recurrence or metastasis were evaluated.
      Growth rate of tumors were compared among various histologic subtypes and Fuhrman
      grades. RESULTS: Of 47 tumors, 27 (57.5%) were clear cell RCCs, 12 (25.5%) were
      multilocular RCCs, and eight (17%) were papillary cystic RCCs. Overall, 26
      (55.3%) tumors were graded as Fuhrman grade 2, 17 (36.1%) were Fuhrman grade 1,
      and one tumor was Fuhrman grade 3. Of the 26 tumors with a minimum of 6 months of
      pretreatment imaging monitoring, 19 (73%) did not show a significant increase in
      tumor size. The differences in mean growth among the Fuhrman grades and different
      subtypes were not statistically significant. The average duration of
      posttreatment follow-up was 51 months. There were no local recurrences among the
      43 patients who underwent posttreatment imaging, except for one patient who had
      metastasis at preoperative clinical presentation. CONCLUSION: Cystic RCCs exhibit
      slow indolent growth, if any, and show no significant metastatic or recurrence
      potential, with excellent clinical outcomes. We raise the need for revisiting
      current imaging protocols that may involve frequent pre-and posttreatment imaging
      in cystic RCCs.

PMID- 23883244
TI  - Automatic selection of tube potential for radiation dose reduction in vascular
      and contrast-enhanced abdominopelvic CT.
AB  - OBJECTIVE: The purpose of this study is to assess the ability of a novel
      automatic tube potential selection tool to reduce radiation dose while
      maintaining diagnostic quality in CT angiography (CTA) and contrast-enhanced
      abdominopelvic CT. MATERIALS AND METHODS: One hundred one CTA examinations and 90
      contrastenhanced abdominopelvic examinations were performed using an automatic
      tube potential selection tool on a 128-MDCT scanner. Two vascular radiologists
      and two abdominal radiologists evaluated the image quality for sharpness, noise,
      artifact, and diagnostic confidence. In a subset of patients who had undergone
      prior studies (CTA, 28 patients; abdominopelvic CT, 25 patients), a side-by-side
      comparison was performed by a separate radiologist. Dose reduction and iodine
      contrast-to-noise ratio resulting from use of the tool were calculated. RESULTS:
      For CTA, 80 or 100 kV was selected for 73% of the scans, with a mean dose
      reduction of 36% relative to the reference 120-kV protocol. For abdominopelvic CT
      examinations, 80 or 100 kV was used for 55% of the scans, with a mean dose
      reduction of 25%. Overall dose reduction relative to the reference 120-kV
      protocol was 25% and 13% for CTA and abdominopelvic CT scans, respectively. Over
      98% of scans had acceptable sharpness, noise texture, artifact, and diagnostic
      confidence for both readers and diagnostic tasks; 94-100% of scans had acceptable
      noise. Iodine contrast-to-noise ratio was significantly higher than (p < 0.001)
      or similar to (p = 0.11) that of prior scans, and equivalent quality was achieved
      despite the dose reduction. CONCLUSION: Automatic tube potential selection
      provides an efficient and quantitativeway to guide the selection of the optimal
      tube potential for CTA and abdominopelvic CT examinations.

PMID- 23883245
TI  - Effects of quality assurance regulatory enforcement on performance of mammography
      systems: evidence from large-scale surveys in Taiwan.
AB  - OBJECTIVE: The Standards for Medical Exposure Quality Assurance in mammography
      systems were enacted on July 1, 2008, in Taiwan. This study aimed to evaluate the
      trends in performance of mammography units before and after the regulation
      started on the basis of annual on-site surveys from 2008 to 2010. MATERIALS AND
      METHODS: On-site measurements were conducted on 215, 205, and 209 mammography
      units in 2008, 2009, and 2010, respectively, which accounted for more than 95% of
      all units in Taiwan. Phantom image quality, average glandular dose (AGD), and
      half-value layer were evaluated on all systems. Processor conditions, compression
      conditions, radiation output, and computed radiography exposure indicators were
      assessed on units participating in mammography screening in 2008 and on all units
      in the later years. Evaluations of maximum compression force and automatic
      exposure control reproducibility were added into the protocol from 2009 onward.
      RESULTS: Mean phantom scores were improved significantly from 2008 to 2009 (11.63
      +/- 1.30 vs 12.31 +/- 0.94, p < 0.05) and remained stable for 2010 (12.35 +/-
      0.87). Mean AGDs were 1.48 +/- 0.47, 1.38 +/- 0.41, and 1.37 +/- 0.42 mGy over
      the 3 years, with a significant reduction from 2008 to 2009 (p < 0.05). For film
      screen mammography systems, variations of sensitometric curves were greatly
      reduced in 2009 and 2010 when compared with 2008. Passing rates were increased
      after the regulation took effect in almost all aspects. CONCLUSION: Results from
      large-scale on-site surveys showed an overall improvement in performance after
      quality assurance in mammography was enforced in Taiwan.

PMID- 23883246
TI  - Ultrasound-guided corticosteroid injections for treatment of greater trochanteric
      pain syndrome: greater trochanter bursa versus subgluteus medius bursa.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of
      corticosteroid injections into the greater trochanteric bursa as opposed to the
      subgluteus medius bursa in patients with greater trochanteric pain syndrome.
      MATERIALS AND METHODS: We retrospectively reviewed 183 injections (149 performed
      in women, 34 performed in men; age range 23-90 years; median, 53 years) performed
      for treatment of greater trochanteric pain syndrome. A 10-cm visual analog scale
      survey was used to assess pain level before the procedure and 14 days after the
      procedure. A 3-mL corticosteroid solution was injected into either the greater
      trochanteric bursa or the subgluteus medius bursa under direct ultrasound
      guidance. Procedure images were retrospectively reviewed to determine the site of
      injection. Diagnostic images obtained at the time of the procedure were also
      reviewed for findings of tendinopathy, bursitis, and enthesopathy. Statistical
      analysis of differences in pain reduction was performed, as was analysis for
      association between pain relief and demographic variables of age, sex, previous
      injections, and ultrasound findings. RESULTS: Sixty-five injections met the
      inclusion criteria; 56 performed in women and nine performed in men (age range,
      30-82 years; median, 53 years). Forty-one injections were into the greater
      trochanteric bursa and 24 into the subgluteus medius bursa. There was a
      statistically significant difference in pain reduction between greater
      trochanteric bursa and subgluteus medius bursa injections with a median pain
      reduction of 3 as opposed to 0 (p < 0.01). There was no statistically significant
      association between pain relief and demographic variables or ultrasound findings.
      CONCLUSION: Corticosteroid injections into the greater trochanteric bursa may be
      more effective than injections into the subgluteus medius bursa for treatment of
      greater trochanteric pain syndrome.

PMID- 23883247
TI  - Spectral Doppler analysis of parathyroid adenoma: correlation between resistive
      index and serum parathyroid hormone concentration.
AB  - OBJECTIVE: The purpose of this study was to evaluate the correlation between
      spectral wave analyses by measuring the resistive index and serum intact
      parathyroid hormone (iPTH) concentration in primary hyperparathyroidism. SUBJECTS
      AND METHODS: From March 2008 to April 2012, 46 consecutively registered patients
      underwent color and spectral Doppler ultrasonography for determination of
      vascularity and vascular resistance of parathyroid adenoma. The color Doppler
      sonographic findings were compared with methoxyisobutylisonitrile (MIBI)
      scintigraphic findings, serum iPTH concentration, and the volume of the gland.
      RESULTS: The mean resistive index in parathyroid adenoma was 0.69 +/- 0.12. The
      study showed a strong negative relation between resistive index and serum iPTH
      concentration. There was a significant negative relation between the volume of
      the gland and the resistive index. CONCLUSION: There is a relation between degree
      of perfusion in parathyroid adenoma and serum iPTH concentration. Resistive index
      may be an objective alternative parameter for determining the vascularity of
      adenoma for monitoring of response to alcohol ablation therapy and medical
      management.

PMID- 23883248
TI  - Effects of low-dose protocols in endovascular treatment of intracranial
      aneurysms: development of workflow task analysis during cerebral endovascular
      procedures.
AB  - OBJECTIVE: Reducing radiation exposure through the use of low-dose protocols
      during cerebral endovascular procedures is recommended, but evaluation of the
      impact on the procedure itself is difficult and subjective. A workflow task
      analysis could provide an objective comparison of two different radiation
      exposure protocols. SUBJECTS AND METHODS: Twenty endovascular aneurysm treatments
      were analyzed using a low-dose protocol (reducing radiation exposure by 20%) in
      10 cases and a normal-dose protocol in the other 10 cases. The procedure was
      subdivided into five phases, each comprising a sequence of tasks. Each task was
      defined as a triplet, associating an action, an instrument, and an anatomic
      structure. A workflow editor was used to record tasks and phases with a tablet
      PC. The total duration of the entire procedure, the duration of each task, and
      the number of task repetitions were isolated and used as the metric. Moreover,
      the tasks involving x-ray use, essential for navigation and treatment phases,
      were separated and analyzed. RESULTS: For the microcatheter navigation and
      treatment phases, no statistically significant difference was found between the
      two radiation exposure protocols. For guide catheter navigation in cervical
      vessels, the total phase duration and total and mean time of tasks specifically
      involving x-ray use increased with age, but there was no difference between the
      two radiation protocols. CONCLUSION: Workflow task analysis of endovascular
      aneurysm treatment shows no difference between low-dose and normal-dose protocols
      in the guide catheter navigation, microcatheter navigation, or treatment phases.

PMID- 23883249
TI  - Diffusion-tensor imaging of small nerve bundles: cranial nerves, peripheral
      nerves, distal spinal cord, and lumbar nerve roots--clinical applications.
AB  - OBJECTIVE: The purpose of this article is to review recent advances in diffusion
      tensor imaging (DTI) and tractography of the cranial and peripheral nerves.
      CONCLUSION: Advances in MR data acquisition and postprocessing methods are
      permitting high-resolution DTI of the cranial and peripheral nerves in the
      clinical setting. DTI offers information beyond routine clinical MRI, and DTI
      findings have implications for the diagnosis and treatment of nerve disease.

PMID- 23883250
TI  - Ultrasound evaluation of costochondral abnormalities in children presenting with
      anterior chest wall mass.
AB  - OBJECTIVE: The purpose of this article is to summarize our experience with the
      use of ultrasound for evaluation of costochondral cartilage deformity in patients
      presenting with an anterior chest wall mass. MATERIALS AND METHODS: From 2007 to
      2012, we identified all patients at our tertiary care children's hospital younger
      than 18 years old who underwent ultrasound for a clinical indication of anterior
      chest wall mass of unknown cause. A pediatric radiologist reviewed all ultrasound
      examinations and other pertinent radiology examinations as well as prior and
      follow-up clinical history and determined the final clinical cause of the mass.
      RESULTS: We identified 16 patients (nine girls and seven boys; age range, 11
      months to 16.1 years; mean, 7.5 years). All patients presented with a firm
      anterior chest wall mass. Three patients had pain. Thirteen patients had prior
      imaging studies, including chest radiography (n = 13), CT of the chest (n = 1),
      MRI of the breast (n = 1), and ultrasound of the chest wall (n = 1). In all prior
      studies the cause of the anterior chest wall mass was missed. Ultrasound showed
      an angular deformity of a single-level (n = 13) or multilevel (n = 1) costal
      cartilage, hypertrophy and elongation with mild angulation of the costal
      cartilage (n = 1), and osteochondroma (n = 1). CONCLUSION: Targeted chest
      ultrasound is a useful diagnostic tool in the evaluation of costochondral
      cartilage deformities and should be considered in children with a firm anterior
      chest wall mass and negative radiography.

PMID- 23883251
TI  - Renal sympathetic denervation: MDCT evaluation of the renal arteries.
AB  - OBJECTIVE: Percutaneous transluminal renal sympathetic denervation is a new
      treatment of refractory systemic hypertension. The purpose of this study was to
      assess the clinical utility of MDCT to evaluate the anatomic configuration of the
      renal arteries in the context of renal sympathetic denervation. MATERIALS AND
      METHODS: Two readers retrospectively evaluated the MDCT renal artery scans of 90
      patients (mean age, 70 +/- 13 years; range, 32-98 years). Analysis included the
      number of renal arteries on each side, ostial shape and size, angle off the
      aorta, branching pattern, degree of tortuosity, and distance to adjacent vascular
      structures. RESULTS: Sixty-five patients had one, 23 had two, and two had three
      renal arteries on one side. One hundred forty-six arteries were funnel-shaped (72
      left and 74 right; mean ostial diameter, 0.9 +/- 0.2 cm tapering to 0.6 +/- 0.1
      cm). The mean tortuosity index was 1.1 (range, 1 [no tortuosity] to 3.1).
      Compared with the left renal artery, the right renal artery was longer (4.0 +/-
      0.9 cm vs 5.0 +/- 1.2 cm, p <= 0.001), originated at a more acute angle on axial
      (67 degrees  vs 98 degrees , p < 0.05) and coronal images (57 degrees  +/- 16
      degrees  vs 65 degrees  +/- 14 degrees , p < 0.05), was significantly closer to
      the superior mesenteric artery (1.0 +/- 0.7 cm vs 1.6 +/- 1.2 cm, p < 0.001), and
      came in closer contact with venous structures (0.0 +/- 0.1 vs 0.2 +/- 0.9, p <
      0.05). CONCLUSION: Our findings suggest MDCT of the renal arteries is an
      informative investigation in patients undergoing renal sympathetic denervation,
      providing data on the number and size of renal branches, ostial shape, and
      proximity to adjacent venous structures.

PMID- 23883252
TI  - Comparison of shear-wave and strain ultrasound elastography in the
      differentiation of benign and malignant breast lesions.
AB  - OBJECTIVE: The purpose of this article is to compare the diagnostic performances
      of shearwave and strain elastography for the differentiation of benign and
      malignant breast lesions. MATERIALS AND METHODS: B-mode ultrasound and shear-wave
      and strain elastography were performed in 150 breast lesions; 71 were malignant.
      BI-RADS final assessment, elasticity values in kilopascals, and elasticity scores
      on a 5-point scale were assessed before biopsy. The results were compared using
      the area under the receiver operating characteristic curve (AUC). RESULTS: The
      AUC for shear-wave elastography was similar to that of strain elastography (0.928
      vs 0.943). The combined use of B-mode ultrasound and either elastography
      technique improved diagnostic performance in the differentiation of benign and
      malignant breast lesions compared with the use of B-mode ultrasound alone (B-mode
      alone, AUC = 0.851; B-mode plus shear-wave elastography, AUC = 0.964; B-mode plus
      strain elastography, AUC = 0.965; p < 0.001). With the best cutoff points of 80
      kPa on shear-wave elastography and a score between 3 and 4 on strain
      elastography, the sensitivity was higher in shear-wave elastography, and
      specificity was higher in strain elastography (95.8% vs 81.7%, p = 0.002; 93.7%
      vs 84.8%, p = 0.016). In cases of infiltrating ductal carcinoma, mean elasticity
      scores were lower in grade 3 than in grade 1 and 2 cancers (p = 0.017) with
      strain elastography causing false-negative findings. CONCLUSION: The diagnostic
      performance of shear-wave and strain elastography was similar. Either
      elastography technique can improve overall diagnostic performance in the
      differentiation of benign and malignant lesions when combined with B-mode
      ultrasound. However, the sensitivity and specificity of shear-wave and strain
      elastography were different according to lesion histologic profile, tumor grade,
      and breast thickness.

PMID- 23883253
TI  - Medicolegal-malpractice and ethical issues in radiology: does interpreting too
      many radiologic studies increase the chance of error?

PMID- 23883254
TI  - Medicolegal-malpractice and ethical issues in radiology: malpractice
      vulnerability of radiology residents and fellows.

PMID- 23883255
TI  - Minimal fat angiomyolipoma: a controversial subtype of classic angiomyolipoma.

PMID- 23883256
TI  - Reply: To PMID 22268181.

PMID- 23883257
TI  - Multivariate analyses are only informative if sufficient information is provided.

PMID- 23883258
TI  - Reply: To PMID 22915433.

PMID- 23883259
TI  - Fungal infection mimicking lung cancer: a potential cause of misdiagnosis.

PMID- 23883260
TI  - Reply: To PMID 22997395.

PMID- 23883261
TI  - Differential diagnosis of focal renal lesions in pediatric patients.

PMID- 23883262
TI  - Reply: To PMID 23169739.

PMID- 23883263
TI  - Portal venous gas secondary to molecular targeted therapy.

PMID- 23883264
TI  - Reply: To PMID 23169717.

PMID- 23883265
TI  - Ocriplasmin is a useful clinical tool; careful case selection will improve
      treatment results.
AB  - This editorial discusses the significance of the first reported case series of
      real-world use of ocriplasmin for treating symptomatic vitreomacular adhesion and
      addresses the importance of case selection in improving treatment results. 

PMID- 23883267
TI  - Employing information systems to shore up retina practices for the next phase of
      health care.

PMID- 23883266
TI  - The evolving paradigm for the treatment of diabetic macular edema.

PMID- 23883268
TI  - Initial outcomes following intravitreal ocriplasmin for treatment of symptomatic
      vitreomacular adhesion.
AB  - BACKGROUND AND OBJECTIVE: When delivered via a single intravitreal injection,
      ocriplasmin can effect proteolytic resolution of symptomatic vitreomacular
      adhesion (VMA). The authors describe their initial clinical experience with
      ocriplasmin at a large academic center. PATIENTS AND METHODS: Retrospective
      review of all patients with symptomatic VMA treated with ocriplasmin from January
      2013 through May 2013 at a single center. RESULTS: Nineteen patients with
      symptomatic VMA received intravitreal ocriplasmin. Eight patients (42%) exhibited
      resolution of VMA. Macular holes in three of six patients (50%) closed after
      injection. A higher proportion of VMA resolution was observed in patients with
      the following baseline characteristics: age less than 65 years, focal adhesions
      less than or equal to 1,500 MUm, presence of macular hole, phakic status, and
      absence of epiretinal membrane. CONCLUSION: Initial clinical outcomes using
      ocriplasmin in this study are consistent with those reported in the phase 3
      clinical trials. Improved clinical results can be achieved with careful case
      selection based on specific baseline characteristics.

PMID- 23883269
TI  - Eight questions with Dr. Puliafito.

PMID- 23883270
TI  - Electrochemically controlled multiple hydrogen bonding between triarylamines and
      imidazoles.
AB  - By increasing the number of amino substituents on triarylamine, the extent of
      hydrogen bonding between the oxidized form of triarylamine and imidazole could be
      electrochemically controlled. Three behaviors, depending on the interaction
      between oxidized amine and imidazole, were obtained in CV patterns. DFT
      calculation was used to confirm that the electron density of protons of the amino
      group decreased as the amino moiety increased. 

PMID- 23883272
TI  - Size-tailored synthesis of silver quasi-nanospheres by kinetically controlled
      seeded growth.
AB  - This paper describes a simple and convenient procedure to synthesize monodisperse
      silver (Ag) quasi-nanospheres with size tunable in a range of 19-140 nm through a
      one-step seeded growth strategy. Acetonitrile was employed as a coordinating
      ligand of a Ag(I) salt in order to achieve a low concentration of elemental Ag
      after reduction and thus suppression of new nucleation events. Since the addition
      of the seeds significantly accelerates the reduction reaction of Ag(I) by
      ascorbic acid, the reaction kinetics was further delicately balanced by tuning
      the reaction temperature, which proved to be critical in producing Ag quasi
      nanospheres with uniform size and shape. This synthesis is highly scalable, so
      that it provides a simple yet very robust process for producing Ag quasi
      nanospheres for many biological, analytical, and catalytic applications which
      often demand samples in large quantity and widely tunable particle sizes. 

PMID- 23883271
TI  - Vitamin D and subsequent all-age and premature mortality: a systematic review.
AB  - BACKGROUND: All-cause mortality in the population<65 years is 30% higher in
      Glasgow than in equally deprived Liverpool and Manchester. We investigated a
      hypothesis that low vitamin D in this population may be associated with premature
      mortality via a systematic review and meta-analysis. METHODS: Medline, EMBASE,
      Web of Science, the Cochrane Library and grey literature sources were searched
      until February 2012 for relevant studies. Summary statistics were combined in an
      age-stratified meta-analysis. RESULTS: Nine studies were included in the meta
      analysis, representing 24,297 participants, 5,324 of whom died during follow-up.
      The pooled hazard ratio for low compared to high vitamin D demonstrated a
      significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D
      levels and all-cause mortality after adjustment for available confounders. In an
      age-stratified meta-analysis, the hazard ratio for older participants was 1.25
      (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).
      CONCLUSIONS: Low vitamin D status is inversely associated with all-cause
      mortality but the risk is higher amongst older individuals and the relationship
      is prone to residual confounding. Further studies investigating the association
      between vitamin D deficiency and all-cause mortality in younger adults with
      adjustment for all important confounders (or using randomised trials of
      supplementation) are required to clarify this relationship.

PMID- 23883273
TI  - Development of a biphasic electroreactor with a wet scrubbing system for the
      removal of gaseous benzene.
AB  - An efficient, continuous flow electroreactor system comprising a scrubbing column
      (for absorption) and a biphasic electroreactor (for degradation) was developed to
      treat gas streams containing benzene. Initial benzene absorption studies using a
      continuous flow bubble column containing absorbents like 40% sulfuric acid, 10%
      silicone oil (3, 5, 10 cSt), or 100% silicone oil showed that 100% silicone oil
      is the most suitable. A biphasic batch electroreactor based on 50 mL of silicone
      oil and 100 mL of activated Co(III) (activated electrochemically) in 40% sulfuric
      acid demonstrated that indirect oxidation of benzene is possible by Co(III).
      Combined experiments on the wet scrubbing column and biphasic electroreactor (BP
      ER) were performed to determine the feasibility of benzene removal, which is
      reside in the silicone oil medium. In semidynamic scrubbing with BP-ER
      experiments using an aqueous electroreactor volume of 2 L, and an inlet gas flow
      and a gaseous benzene concentration were 10 Lmin(-1) and 100 ppm, respectively,
      benzene removal efficiency is 75% in sustainable way. The trend of CO2 evolution
      is well correlated with benzene recovery in the BP-ER. The addition of
      sodiumdodecyl sulfate (SDS) enhanced the recovery of silicone oil without
      affecting benzene removal. This process is promising for the treatment of high
      concentrations of gaseous benzene. 

PMID- 23883274
TI  - Complex pelvic fracture urethral distraction defects revisited.
AB  - OBJECTIVE: This study aimed to establish some guidelines for the definition,
      diagnosis and treatment of complex pelvic fracture urethral distraction defects
      (PFUDD). MATERIAL AND METHODS: A total of 40 patients with complex PFUDD was
      enrolled in this study. Urethral defects were associated with a paraurethral
      bladder base fistula (PBBF) (six patients), urethrorectal fistula (eight),
      urethrocutaneous fistula (nine), urinoma cavity (eight) or bladder neck
      incompetence (nine). In four patients the urethra had been wrongly reconstructed
      into a bladder base fistula (three) or urinoma cavity (one), elsewhere. Repair
      was performed by a perineal anastomotic urethroplasty in 15 patients and by a
      perineoabdominal transpubic procedure in 25. RESULTS: Repair was successful in
      nine out of 15 (60%) patients who received a perineal repair and in 23 out of 25
      (92%) who underwent a perineoabdominal transpubic procedure. Of the eight
      patients with unsuccessful outcomes five were successfully recorrected by
      transpubic urethroplasty. CONCLUSIONS: A PFUDD may be considered as complex if it
      is associated with a PBBF, urethrorectal or urethrocutaneous fistula, urinoma
      cavity, or bladder neck incompetence. Complete excision of a PBBF usually
      requires a perineoretropubic approach. The initial trauma-related urethrorectal
      fistula usually opens into the prostatic urethra and its repair requires an
      abdominal approach, whereas an iatrogenic rectal fistula usually opens into the
      proximal bulbar urethra and can be resolved by a relatively simple perineal
      operation. Excision of a urinoma cavity or urethrocutaneous fistula can usually
      be accomplished from the perineum, while repair of a bladder neck incompetence
      requires an abdominal approach.

PMID- 23883275
TI  - Shifted termination assay (STA) fragment analysis to detect BRAF V600 mutations
      in papillary thyroid carcinomas.
AB  - BACKGROUND: BRAF mutation is an important diagnostic and prognostic marker in
      patients with papillary thyroid carcinoma (PTC). To be applicable in clinical
      laboratories with limited equipment, diverse testing methods are required to
      detect BRAF mutation. METHODS: A shifted termination assay (STA) fragment
      analysis was used to detect common V600 BRAF mutations in 159 PTCs with DNAs
      extracted from formalin-fixed paraffin-embedded tumor tissue. The results of STA
      fragment analysis were compared to those of direct sequencing. Serial dilutions
      of BRAF mutant cell line (SNU-790) were used to calculate limit of detection
      (LOD). RESULTS: BRAF mutations were detected in 119 (74.8%) PTCs by STA fragment
      analysis. In direct sequencing, BRAF mutations were observed in 118 (74.2%)
      cases. The results of STA fragment analysis had high correlation with those of
      direct sequencing (p < 0.00001, kappa = 0.98). The LOD of STA fragment analysis
      and direct sequencing was 6% and 12.5%, respectively. In PTCs with pT3/T4 stages,
      BRAF mutation was observed in 83.8% of cases. In pT1/T2 carcinomas, BRAF mutation
      was detected in 65.9% and this difference was statistically significant (p =
      0.007). Moreover, BRAF mutation was more frequent in PTCs with extrathyroidal
      invasion than tumors without extrathyroidal invasion (84.7% versus 62.2%, p =
      0.001). To prepare and run the reactions, direct sequencing required 450 minutes
      while STA fragment analysis needed 290 minutes. CONCLUSIONS: STA fragment
      analysis is a simple and sensitive method to detect BRAF V600 mutations in
      formalin-fixed paraffin-embedded clinical samples. VIRTUAL SLIDES: The virtual
      slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5684057089135749.

PMID- 23883276
TI  - Iron dissolution of dust source materials during simulated acidic processing: the
      effect of sulfuric, acetic, and oxalic acids.
AB  - Atmospheric organic acids potentially display different capacities in iron (Fe)
      mobilization from atmospheric dust compared with inorganic acids, but few
      measurements have been made on this comparison. We report here a laboratory
      investigation of Fe mobilization of coal fly ash, a representative Fe-containing
      anthropogenic aerosol, and Arizona test dust, a reference source material for
      mineral dust, in pH 2 sulfuric acid, acetic acid, and oxalic acid, respectively.
      The effects of pH and solar radiation on Fe dissolution have also been explored.
      The relative capacities of these three acids in Fe dissolution are in the order
      of oxalic acid > sulfuric acid > acetic acid. Oxalate forms mononuclear bidentate
      ligand with surface Fe and promotes Fe dissolution to the greatest extent.
      Photolysis of Fe-oxalate complexes further enhances Fe dissolution with the
      concomitant degradation of oxalate. These results suggest that ligand-promoted
      dissolution of Fe may play a more significant role in mobilizing Fe from
      atmospheric dust compared with proton-assisted processing. The role of
      atmospheric organic acids should be taken into account in global-biogeochemical
      modeling to better access dissolved atmospheric Fe deposition flux at the ocean
      surface. 

PMID- 23883277
TI  - The chronic pain patient and functional assessment: use of the 6-Minute Walk Test
      in a multidisciplinary pain clinic.
AB  - OBJECTIVE: For chronic pain treatment, guidelines and regulatory agencies have
      defined functional improvement as a primary goal, especially when chronic opioid
      therapy is used. Functional improvement is frequently evaluated by qualitative
      questioning. This pilot study sought to establish a simple and inexpensive
      measure of functional change for a chronic pain population. METHODS: Using a
      multidisciplinary pain clinic standard physical therapy approach for all entering
      chronic pain patients, multiple functional tests were performed, including the 6
      Minute Walk Test. Data was collected by retrospective chart review, at entry to
      the clinic and 3-6 months later and compared using simple t-test statistics on 45
      patients. RESULTS: The average distance walked at center admission was 272.87
      yards. At 3-6 month clinical retesting, the distance had improved significantly
      to 339.04 yards (p<0.0001). NRS scores at 3-6 months were also improved from
      baseline (p<0.001). CONCLUSIONS: While suggestive, this study has significant
      limitations. Not all patients entering into the clinic were included in this
      study, only those who had completed the necessary testing. Further, chart reviews
      are complicated by the accuracy with which data is recorded. This study is
      intriguing and presents positive data for a simple, inexpensive and reproducible
      test for physical functioning in a chronic pain population. Further study is
      warranted based on these descriptive results.

PMID- 23883278
TI  - Impact of stimulus similarity between the probe and the irrelevant items during a
      card-playing deception detection task: the "irrelevants" are not irrelevant.
AB  - Event-related brain potential paradigms for the detection of concealed
      information commonly involve presenting probes embedded within a series of
      irrelevant items. This study investigated the impact of similarity of the
      irrelevant items with the probe. For the task, a card was shown followed by the
      sequential presentation of six "test" cards, one of which was the same as the
      initial card (the probe) along with five "irrelevant" cards that varied in terms
      of similarity with the probe. Participants either identified or denied
      recognition of the probe. The results show that P300 amplitude is modulated by
      stimulus similarity and highlight the importance of the irrelevant items on
      deception detection rates. 

PMID- 23883279
TI  - Vertical platysma myocutaneous flap that sacrifices the facial artery and vein.
AB  - BACKGROUND: Platysma myocutaneous flap (PMF) is a generally used technique for
      defect reconstruction after an oral cancer resection. The aim of the study is to
      present our experience using vertical PMF that sacrificed the facial artery and
      vein for intraoral reconstruction. METHODS: A retrospective review of the medical
      records of 54 patients who underwent vertical PMF that sacrificed the facial
      artery and vein for intraoral reconstruction was performed. A comparison between
      PMF that sacrificed and that preserved the facial vessels was made, and we also
      compared PMF that sacrificed the facial vessels with radial forearm free flap
      (RFFF). Statistics concerning the patients' clinical factors were gathered.
      RESULTS: The mean age of the 54 patients who underwent PMF that sacrificed the
      facial artery and vein was 62.0 +/- 10.98 years. The co-morbid disease rate of
      PMF was 53.7%. The flap size ranged from 12 * 5.5 cm to 7 * 5 cm. Survival of the
      flap was found in all of the cases, with partial necrosis in four cases (7.4%)
      and total loss in none of the cases. The operation time was 5.7 +/- 1.17 h. The
      complication and success rates were 27.8% and 92.6%, respectively. The 3-year and
      5-year survival rates were 77.8% (21/27) and 69.23% (9/13), respectively. The
      majority of the patients (87.0%) in our series were satisfied with the results of
      the surgery. There was no significant difference between PMF that sacrificed or
      that preserved the facial vessels, both in success rate (P = 1) or complication
      rate (P = 0.72). The patients in the PMF group were older than the patients in
      the RFFF group (P = 0.011), the operation time was shorter (P < 0.001), and the
      co-morbid disease rate was higher (P = 0.002). Although the complication rate of
      PMF (15/54, 27.8%) was higher than that of RFFF (2/34, 5.9%) (P = 0.011), their
      success rates were similar (92.6%, 94.1%) (P = 1.00). CONCLUSIONS: Vertical PMF
      that sacrifices the facial artery and vein has specific advantages including in
      ease preparation and limitations. This technique may provide an effective method
      for intraoral reconstruction. Our experience in handling the flap may contribute
      to the success rate.

PMID- 23883280
TI  - svapls: an R package to correct for hidden factors of variability in gene
      expression studies.
AB  - BACKGROUND: Hidden variability is a fundamentally important issue in the context
      of gene expression studies. Collected tissue samples may have a wide variety of
      hidden effects that may alter their transcriptional landscape significantly. As a
      result their actual differential expression pattern can be potentially distorted,
      leading to inaccurate results from a genome-wide testing for the important
      transcripts. RESULTS: We present an R package svapls that can be used to identify
      several types of unknown sample-specific sources of heterogeneity in a gene
      expression study and adjust for them in order to provide a more accurate
      inference on the original expression pattern of the genes over different
      varieties of samples. The proposed method implements Partial Least Squares
      regression to extract the hidden signals of sample-specific heterogeneity in the
      data and uses them to find the genes that are actually correlated with the
      phenotype of interest. We also compare our package with three other popular
      softwares for testing differential gene expression along with a detailed
      illustration on the widely popular Golub dataset. Results from the sensitivity
      analyes on simulated data with widely different hidden variation patterns reveal
      the improved detection power of our R package compared to the other softwares
      along with reasonably smaller error rates. Application on the real-life dataset
      exhibits the efficacy of the R package in detecting potential batch effects from
      the dataset. CONCLUSIONS: Overall, Our R package provides the user with a
      simplified framework for analyzing gene expression data with a wide range of
      hidden variation patterns and delivering a differential gene expression analysis
      with substantially improved power and accuracy.The R package svapls is freely
      available at http://cran.r-project.org/web/packages/svapls/index.html.

PMID- 23883281
TI  - Reappraisal of the outcome of healthcare-associated and community-acquired
      bacteramia: a prospective cohort study.
AB  - BACKGROUND: Healthcare-associated (HCA) bloodstream infections (BSI) have been
      associated with worse outcomes, in terms of higher frequencies of antibiotic
      resistant microorganisms and inappropriate therapy than strict community-acquired
      (CA) BSI. Recent changes in the epidemiology of community (CO)-BSI and treatment
      protocols may have modified this association. The objective of this study was to
      analyse the etiology, therapy and outcomes for CA and HCA BSI in our area.
      METHODS: A prospective multicentre cohort including all CO-BSI episodes in adult
      patients was performed over a 3-month period in 2006-2007. Outcome variables were
      mortality and inappropriate empirical therapy. Adjusted analyses were performed
      by logistic regression. RESULTS: 341 episodes of CO-BSI were included in the
      study. Acquisition was HCA in 56% (192 episodes) of them. Inappropriate empirical
      therapy was administered in 16.7% (57 episodes). All-cause mortality was 16.4%
      (56 patients) at day 14 and 20% (71 patients) at day 30. After controlling for
      age, Charlson index, source, etiology, presentation with severe sepsis or shock
      and inappropriate empirical treatment, acquisition type was not associated with
      an increase in 14-day or 30-day mortality. Only an stratified analysis of 14th
      day mortality for Gram negatives BSI showed a statically significant difference
      (7% in CA vs 17% in HCA, p = 0,05). Factors independently related to inadequate
      empirical treatment in the community were: catheter source, cancer, and previous
      antimicrobial use; no association with HCA acquisition was found. CONCLUSION: HCA
      acquisition in our cohort was not a predictor for either inappropriate empirical
      treatment or increased mortality. These results might reflect recent changes in
      therapeutic protocols and epidemiological changes in community pathogens. Further
      studies should focus on recognising CA BSI due to resistant organisms
      facilitating an early and adequate treatment in patients with CA resistant BSI.

PMID- 23883282
TI  - Biased interpretation and memory in children with varying levels of spider fear.
AB  - This study investigated multiple cognitive biases in children simultaneously, to
      investigate whether spider-fearful children display an interpretation bias, a
      recall bias, and source monitoring errors, and whether these biases are specific
      for spider-related materials. Furthermore, the independent ability of these
      biases to predict spider fear was investigated. A total of 121 children filled
      out the Spider Anxiety and Disgust Screening for Children (SADS-C), and they
      performed an interpretation task, a memory task, and a Behavioural Assessment
      Test (BAT). As expected, a specific interpretation bias was found: Spider-fearful
      children showed more negative interpretations of ambiguous spider-related
      scenarios, but not of other scenarios. We also found specific source monitoring
      errors: Spider-fearful children made more fear-related source monitoring errors
      for the spider-related scenarios, but not for the other scenarios. Only limited
      support was found for a recall bias. Finally, interpretation bias, recall bias,
      and source monitoring errors predicted unique variance components of spider fear.

PMID- 23883283
TI  - The complete mitochondrial genome sequence of the Korean hare (Lepus coreanus).
AB  - The complete mitogenome of the Korean hare (Lepus coreanus) was determined by the
      long and accurate polymerase chain reaction and primer-walking methods. The
      mitogenome of the Korean hare is 17,472 bp in length and contains sequences that
      encode 13 protein genes, 22 tRNAs, 2 rRNAs and a noncoding control region. The
      mitogenome is arranged in an identical order to that found in most other
      vertebrates. All mitochondrial genes are encoded on the heavy strand, except for
      eight tRNA genes and the ND6 gene. The control region contains putative
      termination associated elements, conserved sequence blocks and short and long
      tandem repeats motifs. 

PMID- 23883284
TI  - Selective androgen receptor modulators: in vitro and in vivo metabolism and
      analysis.
AB  - For future targeted screening in National Residue Control Programmes, the
      metabolism of seven SARMs, from the arylpropionamide and the quinolinone classes,
      was studied in vitro using S9 bovine liver enzymes. Metabolites were detected and
      identified with ultra-performance liquid chromatography (UPLC) coupled to time-of
      flight mass spectrometry (ToF-MS) and triple quadrupole mass spectrometry (QqQ
      MS). Several metabolites were identified and results were compared with
      literature data on metabolism using a human cell line. Monohydroxylation, nitro
      reduction, dephenylation and demethylation were the main S9 in vitro metabolic
      routes established. Next, an in vivo study was performed by oral administration
      of the arylpropionamide ostarine to a male calf and urine samples were analysed
      with UPLC-QToF-MS. Apart from two metabolites resulting from hydroxylation and
      dephenylation that were also observed in the in vitro study, the bovine in vivo
      metabolites of ostarine resulted in glucuronidation, sulfation and carboxylation,
      combined with either a hydroxylation or a dephenylation step. As the intact
      mother compounds of all SARMs tested are the main compounds present after in
      vitro incubations, and ostarine is still clearly present in the urine after the
      in vivo metabolism study in veal calves, the intact mother molecules were
      selected as the indicator to reveal treatment. The analytical UPLC-QqQ-MS/MS
      procedure was validated for three commercially available arylpropionamides
      according to European Union criteria (Commission Decision 2002/657/EC), and
      resulted in decision limits ranging from 0.025 to 0.05 ug l-1 and a detection
      capability of 0.025 ug l-1 in all cases. Adequate precision and intra-laboratory
      reproducibility (relative standard deviation below 20%) were obtained for all
      SARMs and the linearity was 0.999 for all compounds. This newly developed method
      is sensitive and robust, and therefore useful for confirmation and quantification
      of SARMs in bovine urine samples for residue control programmes and research
      purposes.

PMID- 23883285
TI  - Interleukin-4, interleukin-4 receptor, and interleukin-18 polymorphisms and
      rheumatoid arthritis: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to determine whether the functional
      interleukin-4 (IL-4) -590 C/T, IL-4 receptor (IL-4R) 1902 G/A, IL-18 -607 C/A,
      and -137 G/C polymorphisms polymorphisms confer susceptibility to rheumatoid
      arthritis (RA). METHODS: Meta-analysis was conducted on the associations between
      these IL-4, IL-4R, and IL-18 polymorphisms and RA. RESULTS: A total of 12
      comparative studies were included in this meta-analysis. Meta-analysis of the IL
      4 -590 C/T polymorphism showed an association in all study subjects and Europeans
      (OR for the TT genotype = 2.280, 95% CI = 1.315-3.952, p = 0.003; OR = 2.139, 95%
      CI = 1.089-4.199, p = 0.027). However, meta-analysis showed no association
      between RA and the IL-4R 1902 G allele in all study subjects and Europeans. Meta
      analysis showed no association between RA and the IL-18 -607 C allele (OR =
      1.159, 95% CI = 0.967-1.387, p = 0.110). Meta-analysis of the IL-18 -137 G/C
      polymorphism revealed no association between RA and the IL-18 -137 G/C
      polymorphism. CONCLUSIONS: This meta-analysis demonstrates that the IL-4 -590 T/C
      polymorphism is associated with susceptibility to RA in Europeans, but the IL-4R
      + 1902 G/A, IL-18 -607 C/A and -137 G/C polymorphisms are not associated with RA.

PMID- 23883286
TI  - Development of an enzyme-linked immunosorbent assay for cyhalothrin.
AB  - In the present study, we obtained a specific monoclonal antibody (cross-reaction
      to analogues <5%) against cyhalothrin using two haptens. After 7 reaction steps,
      3-cyano-[(cis)-3-(2-chloro-3, 3, 3-trifluoroethenyl-2, 2-dimethyl)-cyclopropane
      carbonyloxy]-phenoxybenzyl propanoic acid was prepared with yield 35.9%. Four
      coating antigens and two immunogens were prepared. A heterologous enzyme-linked
      immunosorbent assay for cyhalothrin was established with the 50% inhibition
      concentration (IC50, 13.26 +/- 1.23 ng mL(-1)) after optimizing various
      parameters including coating antigens, blocking agents, ionic strength, pH value
      and methanol concentration in the assay buffer. To evaluate the proposed
      immunoassay, spiked samples from river, tap water and drinking water at three
      levels (0.2, 1.0, 5.0 mg L(-1)) were tested after simple dilution. The mean
      recoveries ranged from 75.4% to 97.7% with coefficient of variation 5.1%-11.6%.
      The results from the above indicated the potencies of this ELISA in cyhalothrin
      analysis. 

PMID- 23883287
TI  - Mini-implant stability at the initial healing period: a clinical pilot study.
AB  - OBJECTIVE: To evaluate the changes of mini-implant stability over the initial
      healing period in humans. MATERIAL AND METHODS: A sample of 19 consecutively
      treated patients (mean age 15.5 +/- 7.3 years) was examined. In each patient, a
      mini-implant of a size of 2 * 9 mm was inserted into the anterior palate. Implant
      stability was assessed using resonance frequency analysis (RFA) immediately after
      insertion (T0), 2 weeks later (T1), 4 weeks later (T2), and 6 weeks later (T3).
      Insertion depth (ID) and the maximum insertion torque (IT) were measured. Data
      were tested for correlations between RFA, ID, and IT. All RFA values were tested
      for statistically significant differences between the different times. RESULTS:
      The mean ID was 7.5 +/- 0.6 mm, and the mean IT was 16.8 +/- 0.6 Ncm. A
      correlation was found between RFA and ID (r = .726, P < .0001), whereas no
      correlations between RFA and IT or between IT and ID were observed. From T0 to
      T1, the stability (36.1 +/- 6.1 implant stability quotient [ISQ]) decreased
      nonsignificantly by 4.9 +/- 6.1 ISQ values (P > .05). Between T1 and T2, the
      stability decreased highly significantly (P < .001) by 7.9 +/- 5.9 ISQ values.
      From T2 on, RFA remained nearly unchanged (-1.7 +/- 3.5 ISQ; P > .05).
      CONCLUSIONS: Mini-implant stability is subject to changes during the healing
      process. During weeks 3 and 4, a significant decrease of the stability was
      observed. After 4 weeks, the stability did not change significantly.

PMID- 23883288
TI  - Precision vs flexibility in GPCR signaling.
AB  - The G protein coupled receptor (GPCR) rhodopsin activates the heterotrimeric G
      protein transducin (Gt) to transmit the light signal into retinal rod cells. The
      rhodopsin activity is virtually zero in the dark and jumps by more than one
      billion fold after photon capture. Such perfect switching implies both high
      fidelity and speed of rhodopsin/Gt coupling. We employed Fourier transform
      infrared (FTIR) spectroscopy and supporting all-atom molecular dynamics (MD)
      simulations to study the conformational diversity of rhodopsin in membrane
      environment and extend the static picture provided by the available crystal
      structures. The FTIR results show how the equilibria of inactive and active
      protein states of the receptor (so-called metarhodopsin states) are regulated by
      the highly conserved E(D)RY and Yx7K(R) motives. The MD data identify an
      intrinsically unstructured cytoplasmic loop region connecting transmembrane
      helices 5 and 6 (CL3) and show how each protein state is split into
      conformational substates. The C-termini of the Gtgamma- and Gtalpha-subunits
      (GalphaCT and GgammaCT), prepared as synthetic peptides, are likely to bind
      sequentially and at different sites of the active receptor. The peptides have
      different effects on the receptor conformation. While GgammaCT stabilizes the
      active states but preserves CL3 flexibility, GalphaCT selectively stabilizes a
      single conformational substate with largely helical CL3, as it is found in
      crystal structures. Based on these results we propose a mechanism for the fast
      and precise signal transfer from rhodopsin to Gt, which assumes a stepwise and
      mutual reduction of their conformational space. The mechanism relies on conserved
      amino acids and may therefore underlie GPCR/G protein coupling in general. 

PMID- 23883289
TI  - Quantitative mass spectrometry analysis of intact hemoglobin A2 by precursor ion
      isolation and detection.
AB  - Precise and accurate quantification of proteins is essential in clinical
      laboratories. Here, we present a mass spectrometry (MS)-based method for the
      quantification of intact proteins in an ion trap mass spectrometer. The developed
      method is based on the isolation and detection of precursor ions for the
      quantification of the corresponding signals. The method was applied for the
      quantification of hemoglobin (Hb) A2, a marker used for the diagnosis of a beta
      thalassemia trait. The alpha and delta globin chains, corresponding to total Hb
      and HbA2, respectively, were isolated in the ion trap at specific charge states
      and ejected without activation. Areas of the corresponding isolated precursor
      ions were used to calculate the delta to alpha ratio. Three series of
      quantifications were performed on 7 different days. The standard curve fitted
      linearly (R(2) = 0.9982) and allowed quantification of HbA2 over a concentration
      range from 3% to 18% of total Hb. Analytical imprecision ranged from 3.5% to
      5.3%, which is enough to determine if the HbA2 level is below 3.5% or above 3.7%.
      In conclusion, our method reaches precision requirements that would be acceptable
      for the quantitative measurement of diagnostic proteins, such as HbA2, in
      clinical laboratories. 

PMID- 23883290
TI  - Effect of changes in a food frequency questionnaire: comparing data from two
      national dietary survey instruments among 12-month-old infants.
AB  - BACKGROUND: National dietary surveys among Norwegian 12-months olds have been
      conducted twice: in 1999 and 2007. At both time-points diet were assessed by a
      semi-quantitative food frequency questionnaire (SFFQ) (the SFFQ-1999 and the SFFQ
      2007). Modifications in the SFFQ-2007 compared to the SFFQ-1999 have been made;
      therefore, the objective of the present study has been to explore the
      comparability of the data obtained by the two questionnaires. Moreover,
      reliability of maternal recall of infant feeding practices was assessed. METHODS:
      Three hundred Norwegian infants born in April 2007 were invited to participate by
      completing both the SFFQ-1999 and the SFFQ-2007. An invitation letter and one of
      two questionnaires were sent by mail to the mother/parents about two weeks before
      the child turned 12 months of age. The study had a cross-over design where half
      of the sample received the SFFQ-1999 first and then about 2-3 weeks later they
      received the SFFQ-2007. The second half received the SFFQ-2007 first, and then 2
      3 weeks later they received the SFFQ-1999. RESULTS: Ninety three participants
      completed both questionnaires (SFFQ-1999 and SFFQ-2007). For nutrients, the
      largest significant differences between the questionnaires were found for intake
      of vitamin D and added sugar, where added sugar was reported lower and vitamin D
      was reported higher with the SFFQ-2007 compared to the SFFQ-1999. For food items,
      lower intake of yoghurt and higher intake of vegetables and fish were observed
      with the SFFQ-2007 compared to the SFFQ-1999. In addition, reliable answers with
      regard to breastfeeding status, age for breastfeeding cessation and age for
      introducing solid foods were found. CONCLUSION: There was reasonable
      comparability between the two questionnaires for most nutrients and foods. The
      differences between the two questionnaires could mainly be explained by
      modifications that had occurred over time, where changes in the food composition
      databases used and especially changes in commercial recipes with regard to baby
      food products seemed to be of major importance. The differences are important to
      take into account when interpreting dietary trends among Norwegian 12 month-olds
      in the period from 1999 to 2007. This study also implies that maternal recall of
      infant feeding practices is reliable.

PMID- 23883291
TI  - Phototunable surface interactions.
AB  - Photoresponsive polymer brushes constitute an attractive platform for tuning
      surface properties and functionality. Since the degree of photoconversion can be
      controlled by the light dose, functional states with intermediate properties
      between those of the nonexposed and fully exposed brushes are accessible. Here we
      investigate the light-modulated interfacial, adhesion, and frictional properties
      of photosensitive polymer brushes with a methacrylate backbone and ionizable 
      COOH side groups modified with the photoremovable group 6
      nitroveratryloxycarbonyl (NVOC). The original brush (PNVOCMA) gradually changes
      into a charged poly(methacrylic acid) (PMAA) brush upon exposure to ultraviolet
      light due to the photoremoval of the chromophore and generation of free COOH
      groups. We show how the physical properties of the brush can be gradually tuned
      with the exposure dose using condensation microscopy, atomic force microscopy
      (AFM), force mapping, and friction force spectroscopy. 

PMID- 23883292
TI  - Enhanced room-temperature corrosion of copper in the presence of graphene.
AB  - This paper reports the enhancement of long-term oxidation of copper at room
      temperature by a graphene coating. Previous studies showed that graphene is an
      effective anticorrosion barrier against short-term thermal and electrochemical
      oxidation of metals. Here, we show that a graphene coating can, on the contrary,
      accelerate long-term oxidation of an underlying copper substrate in ambient
      atmosphere at room temperature. After 6 months of exposure in air, both Raman
      spectroscopy and energy-dispersive X-ray spectroscopy indicated that graphene
      coated copper foil had a higher degree of oxidation than uncoated foil, although
      X-ray photoelectron spectroscopy showed that the surface concentration of Cu(2+)
      was higher for the uncoated sample. In addition, we observed that the oxidation
      of graphene-coated copper foil was not homogeneous and occurred within micrometer
      sized domains. The corrosion enhancement effect of graphene was attributed to its
      ability to promote electrochemical corrosion of copper. 

PMID- 23883293
TI  - First synthesis of a stable isotope of Ochratoxin A metabolite for a reliable
      detoxification monitoring.
AB  - Due to its toxicity and presence in numerous food products, Ochratoxin A (OTA)
      has drawn attention for decades. This article summarizes the first synthesis of a
      labeled analogue of Ochratoxin alpha (OTalpha), one of the main products
      generated by the metabolization of OTA by microorganisms. This synthesis also led
      to a new labeled analogue of OTA with the deuteration located on the
      dihydroisocoumarin moiety allowing thus both the accurate quantification of OTA
      and OTalpha and the establishing of a reliable detoxification rate. 

PMID- 23883294
TI  - Preferred treatment frequency in patients receiving androgen deprivation therapy
      for advanced prostate cancer.
AB  - OBJECTIVE: The aim of this study was to assess patient preference regarding the
      length of treatment intervals of androgen deprivation therapy (ADT) with
      gonadotropin-releasing hormone agonists for prostate cancer. MATERIAL AND
      METHODS: The study was conducted as a questionnaire-based, cross-sectional study
      at a large university hospital. A specific questionnaire was developed based on
      current literature, clinical experience and a pilot phase of the study. The
      primary endpoint was preferred treatment frequency. Secondary outcome measures
      included reasons for preferred treatment frequency, treatment satisfaction and
      side-effects. Overall, 238 men receiving ADT for prostate cancer were presented
      with the questionnaire between September 2011 and May 2012. Descriptive
      statistics, the chi-squared test and multiple regression were used for analyses.
      RESULTS: In total, 176 questionnaires (74%) were available for analysis. A total
      of 38.1% of participants preferred frequent treatment ("Every month", "Every
      third month"), 32.4% preferred infrequent treatment ("Every sixth month", "Every
      twelfth month") and 29.6% stated that length of the treatment intervals made no
      difference (p = 0.37). Patients with disease progression were most likely to
      prefer frequent treatment (odds ratio 4.4, 95% confidence interval 1.9-10.4).
      Overall, 84.1% were satisfied with treatment while one patient (0.6%) was
      dissatisfied. Nine per cent indicated severe side-effects. CONCLUSIONS: Less
      frequent ADT treatment may help to lower the pressure on healthcare systems and
      may be of benefit for a large group of patients. However, it cannot be prescribed
      blindly without possibly affecting patient satisfaction. The choice of treatment
      intervals should be made in collaboration between the physician and the patient.

PMID- 23883295
TI  - Transposon fingerprinting using low coverage whole genome shotgun sequencing in
      cacao (Theobroma cacao L.) and related species.
AB  - BACKGROUND: Transposable elements (TEs) and other repetitive elements are a large
      and dynamically evolving part of eukaryotic genomes, especially in plants where
      they can account for a significant proportion of genome size. Their dynamic
      nature gives them the potential for use in identifying and characterizing crop
      germplasm. However, their repetitive nature makes them challenging to study using
      conventional methods of molecular biology. Next generation sequencing and new
      computational tools have greatly facilitated the investigation of TE variation
      within species and among closely related species. RESULTS: (i) We generated low
      coverage Illumina whole genome shotgun sequencing reads for multiple individuals
      of cacao (Theobroma cacao) and related species. These reads were analysed using
      both an alignment/mapping approach and a de novo (graph based clustering)
      approach. (ii) A standard set of ultra-conserved orthologous sequences (UCOS)
      standardized TE data between samples and provided phylogenetic information on the
      relatedness of samples. (iii) The mapping approach proved highly effective within
      the reference species but underestimated TE abundance in interspecific
      comparisons relative to the de novo methods. (iv) Individual T. cacao accessions
      have unique patterns of TE abundance indicating that the TE composition of the
      genome is evolving actively within this species. (v) LTR/Gypsy elements are the
      most abundant, comprising c.10% of the genome. (vi) Within T. cacao the
      retroelement families show an order of magnitude greater sequence variability
      than the DNA transposon families. (vii) Theobroma grandiflorum has a similar TE
      composition to T. cacao, but the related genus Herrania is rather different, with
      LTRs making up a lower proportion of the genome, perhaps because of a massive
      presence (c. 20%) of distinctive low complexity satellite-like repeats in this
      genome. CONCLUSIONS: (i) Short read alignment/mapping to reference TE contigs
      provides a simple and effective method of investigating intraspecific differences
      in TE composition. It is not appropriate for comparing repetitive elements across
      the species boundaries, for which de novo methods are more appropriate. (ii)
      Individual T. cacao accessions have unique spectra of TE composition indicating
      active evolution of TE abundance within this species. TE patterns could
      potentially be used as a "fingerprint" to identify and characterize cacao
      accessions.

PMID- 23883296
TI  - "Tertius gaudens": germplasm exchange networks and agroecological knowledge among
      home gardeners in the Iberian Peninsula.
AB  - BACKGROUND: The idea that knowledge flows through social networks is implicit in
      research on traditional knowledge, but researchers have paid scant attention to
      the role of social networks in shaping its distribution. We bridge those two
      bodies of research and investigate a) the structure of network of exchange of
      plant propagation material (germplasm) and b) the relation between a person's
      centrality in such network and his/her agroecological knowledge. METHODS: We
      study 10 networks of germplasm exchange (n = 363) in mountain regions of the
      Iberian Peninsula. Data were collected through participant observation, semi
      structured interviews, and a survey. RESULTS: The networks display some
      structural characteristics (i.e., decentralization, presence of external actors)
      that could enhance the flow of knowledge and germplasm but also some
      characteristics that do not favor such flow (i.e., low density and
      fragmentation). We also find that a measure that captures the number of contacts
      of an individual in the germplasm exchange network is associated with the
      person's agroecological knowledge. CONCLUSION: Our findings highlight the
      importance of social relations in the construction of traditional knowledge.

PMID- 23883297
TI  - Predictors of reading fluency in Italian orthography: evidence from a cross
      sectional study of primary school students.
AB  - This study investigates the role of linguistic and visuospatial attentional
      processes in predicting reading fluency in typical Italian readers attending
      primary school. Tasks were administered to 651 children with reading fluency z
      scores > -1.5 standard deviation to evaluate their phonological awareness, rapid
      automatized naming (RAN), verbal short-term memory, vocabulary, visual search
      skills, verbal-visual recall, and visual-spatial attention. Hybrid models
      combining confirmatory factor analysis and path analysis were used to evaluate
      the data obtained from younger (first and second grade) and older (third-fifth
      grade) children, respectively. The results showed that phonological awareness and
      RAN played a significant role among younger children, while also vocabulary,
      verbal short-term memory, and visuospatial attention were significant factors
      among older children. 

PMID- 23883299
TI  - Microscopic observation of metal-containing particles from Chinese continental
      outflow observed from a non-industrial site.
AB  - Atmospheric metal-containing particles adversely affect human health because of
      their physiological toxicity. Mixing state, size, phase, aspect ratio, and
      sphericity of individual metal-containing particles collected in Hong Kong air in
      winter are examined through transmission electron microscopy (TEM). Eighteen
      percent of the sulfate particles have one or more tiny metal inclusions. Size
      distributions of metal and fly ash particles (or inclusions) with diameters from
      15 nm to 2.7 MUm show the same peak at 210 nm. The major metal particles were
      classified as Fe-rich (e.g., hematite), Zn-rich (e.g., zinc sulfate and zinc
      oxide), Pb-rich (e.g., anglesite), Mn-rich, and As-rich, which were likely
      emitted from industries and coal-fired power plants at high temperatures in
      mainland China. Compared to fly ash and S-rich particles, metal particles display
      a lower sphericity of 0.51 and a higher aspect ratio of 1.47, which means their
      shapes are poorly defined. The elemental mapping of individual particles reveal
      that sulfate areas without metal inclusions also contain minor Fe, Mn, or Zn.
      Therefore, the internal mixing of metals and acidic constituents likely
      solubilize metals and modify metal inclusion shapes. Solubilization of metals in
      airborne particles can extend their toxicity into nontoxicity parts in the
      particles. The structure of the metal-containing particles may provide important
      information for assessing health effects of fine sulfate and nitrate particles
      with metal inclusions in urban areas. 

PMID- 23883301
TI  - Combinatorial synthesis of Cu/(Ta(x)Nb(1-x))2O5 stack structure for nanoionics
      type ReRAM device.
AB  - Resistive random access memory (ReRAM) has been proposed as a new application for
      oxide materials. We have proposed a Cu electrode/dielectric oxide/bottom
      electrode stack structure as a potential ReRAM material that is compatible with
      the LSI process. Control of the switching voltage and the initial conductive
      filament formation process is beneficial for actual applications. To control the
      switching property by controlling the valence state of metals, we investigated
      the Ta-Nb binary oxide ((TaxNb1-x)2O5) system as a dielectric oxide layer using a
      combinatorial method. A combinatorial pulsed laser deposition method was used to
      fabricate the (TaxNb1-x)2O5 system systematically on a Pt/Si substrate. X-ray
      photoelectron spectroscopy revealed defect formation relating to Ta and the
      compensation of oxygen vacancies caused by a change in the valence number of Nb.
      As the Ta content decreased, there were a decrease in the threshold voltage of
      the low resistive state and an enhancement of the leakage current, meaning that
      the switching properties can be controlled by controlling the (TaxNb1-x)2O5
      system. 

PMID- 23883298
TI  - The therapeutic potential of small-conductance KCa2 channels in neurodegenerative
      and psychiatric diseases.
AB  - INTRODUCTION: KCa2 or small-conductance Ca(2+)-activated K(+) channels (SK) are
      expressed in many areas of the central nervous system where they participate in
      the regulation of neuronal afterhyperpolarization and excitability, and also
      serve as negative feedback regulators on the glutamate-NMDA pathway. AREAS
      COVERED: This review focuses on the role of KCa2 channels in learning and memory
      and their potential as therapeutic targets for Alzheimer's and Parkinson's
      disease, ataxia, schizophrenia and alcohol dependence. EXPERT OPINION: There
      currently exists relatively solid evidence supporting the use of KCa2 activators
      for ataxia. Genetic KCa2 channel suppression in deep cerebellar neurons induces
      ataxia, while KCa2 activators like 1-EBIO, SKA-31 and NS13001 improve motor
      deficits in mouse models of episodic ataxia (EA) and spinal cerebellar ataxia
      (SCA). Use of KCa2 activators for ataxia is further supported by a report that
      riluzole improves ataxia in a small clinical trial. Based on accumulating
      literature evidence, KCa2 activators further appear attractive for the treatment
      of alcohol dependence and withdrawal. Regarding Alzheimer's disease, Parkinson's
      disease and schizophrenia, further research, including long-term studies in
      disease relevant animal models, will be needed to determine whether KCa2 channels
      constitute valid targets and whether activators or inhibitors would be needed to
      positively affect disease outcomes.

PMID- 23883300
TI  - Shrink pattern of breast cancer after neoadjuvant chemotherapy and its
      correlation with clinical pathological factors.
AB  - BACKGROUND: Breast conservation therapy (BCS) after neoadjuvant chemotherapy
      (NCT) can improve patients' quality of life. Currently used intraoperative
      examination for negative margins may not be sufficient to detect microresidual
      foci, which are a risk factor for local recurrence. This study was conducted to
      investigate the shrinking pattern of breast cancer and residual tumors as a risk
      factor for BCS after NCT. METHODS: Ninety women with stage II or III invasive
      ductal carcinoma who achieved partial response after NCT with paclitaxel and
      epirubicin were enrolled. All patients had undergone modified radical mastectomy.
      One-half of the surgical specimens were subjected to subserial sectioning.
      Pathological changes of tumor bed and pericancerous tissues were examined with an
      optical microscope. The levels of estrogen receptors, progesterone receptors and
      HER2 were analyzed by immnohistochemical staining. RESULTS: The residual tumors
      were classified into three types according to their microscopic morphology:
      solitary lesion, multifocal and patchlike lesions, and main residual tumor with
      satellite lesions. Type I residual tumors were found in 55 patients (61%), type
      II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were
      often associated with larger primary tumors. The types of residual tumors were
      not correlated with the status of hormone receptors or HER2. CONCLUSION: Three
      types of residual tumors were observed after NCT. The solitary residual tumor is
      most common, but main residual tumors with satellite lesions are most likely to
      cause local recurrence after BCS. Subserial sectioning would improve the
      identification of microfoci and patient survival after BCS.

PMID- 23883302
TI  - Application of multiple regression analysis in optimization of anastrozole-loaded
      PLGA nanoparticles.
AB  - The present investigation deals with development of anastrozole-loaded PLGA
      nanoparticles (NPs) as an alternate to conventional cancer therapy. The NPs were
      prepared by nanoprecipitation method and optimized using multiple regression
      analysis. Independent variables included drug:polymer ratio (X1), polymer
      concentration in organic phase (X2) and surfactant concentration in aqueous phase
      (X3) while dependent variables were percentage drug entrapment (PDE) and particle
      size (PS). Results of desirability criteria, check point analysis and normalized
      error were considered for selecting the formulation with highest PDE and lowest
      PS. Prepared NPs were characterized for zeta potential, transmission electron
      microscopy (TEM), differential scanning calorimetry (DSC) and in vitro drug
      release studies. DSC and TEM studies indicated absence of any drug-polymer
      interaction and spherical nature of NPs, respectively. In vitro drug release
      showed biphasic pattern exhibiting Fickian diffusion-based release mechanism.
      This delivery system of anastrozole is expected to reduce the side effects
      associated with the conventional cancer therapy by reducing dosing frequency.

PMID- 23883303
TI  - Pd(OAc)2-catalyzed C-H activation/C-O cyclization: mechanism, role of oxidant
      probed by density functional theory.
AB  - A series of density functional theory determinations have been carried out to
      characterize Pd(OAc)2-catalyzed C-H activation and subsequent intramolecular C-O
      bond-coupling of phenyl-tert-butanol in perfluorobenzene (C6F6) solvent. Full,
      nontruncated models of the real chemical transformations were studied, with
      structures in agreement with recent X-ray determinations. Conformational analyses
      have provided thermodynamic validity of the geometric structures used. The
      B3LYP/DZVP and B3LYP/BS1 methods (BS1 = TZVP(H,C,O) + SDD(Pd,I)) were
      comparatively employed, with C6F6 solvent contributions accounted for by the
      IDSCRF method; key transition states were confirmed by intrinsic reaction
      coordinate determinations. The novel reaction mechanism proposed was divided into
      the following four steps: C-H activation, oxidation, reductive elimination,
      catalyst recovery. Two competing reaction routes were quantitatively compared,
      differing in the oxidation state of Pd (+2 vs +4). Results reveal the pathway
      involving Pd(IV) intermediates to be more spontaneous and, therefore, more
      probable than the Pd(II) path, the latter hindered by a kinetically inaccessible
      reductive elimination step, with total energy and free energy barriers of 41.0
      and 38.6 kcal.mol(-1), respectively. The roles played by the oxidant and Pd(IV)
      species have also been addressed through Bader's atoms-in-molecules wave function
      analyses, providing a quantitative electronic metric for C-H activation
      chemistry. 

PMID- 23883304
TI  - Carboxylate-directed in vivo assembly of virus-like nanorods and tubes for the
      display of functional peptides and residues.
AB  - Uniform dimensions and genetic tractability make filamentous viruses attractive
      templates for the display of functional groups used in materials science, sensor
      applications, and vaccine development. However, active virus replication and
      recombination often limit the usefulness of these viruses for such applications.
      To circumvent these limitations, genetic modifications of selected negatively
      charged intersubunit carboxylate residues within the coat protein of tobacco
      mosaic virus (TMV) were neutralized so as to stabilize the assembly of rod-shaped
      virus-like particles (VLPs) within bacterial expression systems. Here we show
      that TMV-VLP nanorods are easily purified, stable, and can be programmed in a
      variety of configurations to display functional peptides for antibody and small
      molecule binding. 

PMID- 23883305
TI  - Bone tissue amount related to upper incisors inclination.
AB  - OBJECTIVE: To evaluate the amount of buccal and lingual supporting bone tissue of
      60 upper central incisors and the relationship with their inclination. MATERIALS
      AND METHODS: Thirty healthy adult patients with no previous orthodontic treatment
      were evaluated using cone-beam computed tomography. Cross-sectional views were
      analyzed to check the amount of the bone tissue on the cervical (cervical buccal
      thickness/CBT; lingual/CLT), middle (middle buccal thickness/MBT; lingual/MLT),
      and apical regions (apical buccal thickness/ABT; lingual/ALT). The Pearson
      correlation, linear regression, and analysis of variance tests were used (P <
      .05). RESULTS: The values of ABT of both teeth (11, right upper central incisor;
      21, left upper central incisor) were significantly increased with the increase in
      the angle between the axis of the upper central incisor and the palatal plane
      (1/PP) (tooth 11 P  =  .034; tooth 21 P  =  .009), yet without a strong linear
      correlation. At the buccal and lingual surfaces, the mean apical supporting bone
      tissue was significantly greater than the other areas, and the middle region
      significantly greater than the cervical (P < .001). CONCLUSIONS: For both
      surfaces (buccal and lingual), the amount of bone tissue in the apical region was
      significantly higher than the middle and cervical regions, and the middle region
      was significantly higher than the cervical region. In relation to the upper
      central incisor's inclination, the higher the 1/PP the higher was ABT. However,
      the coefficient values for both teeth were low.

PMID- 23883306
TI  - Dental anomaly pattern (DAP): agenesis of mandibular second premolar, distal
      angulation of its antimere and delayed tooth formation.
AB  - OBJECTIVE: To test the null hypotheses that children with unilateral agenesis of
      the mandibular second premolar (MnP2) do not show (1) greater distal angulation
      of the unerupted antimere and (2) delayed tooth formation compared with children
      without agenesis. MATERIALS AND METHODS: Panoramic radiographs of 38 patients
      with unilateral aplasia of MnP2 were retrospectively examined and compared to a
      non-agenesic control group of 82 patients. Ages ranged from 8 to 15 years.
      Contralateral mandibular deciduous second molars were present for all
      participants. Each unerupted MnP2 was traced, and its developmental stage and
      angulation were recorded (measured with the distal angle and the premolar-molar
      angle). Dental age was evaluated using the Haavikko method. Student's t-test was
      performed to identify significant differences between the compared groups. The
      significance level for statistical testing was set at P < .05. RESULTS: The
      results indicated a 9.5 degrees  decrease in the distal angle and a 13.2 degrees 
      increase in the premolar-molar angle for the unerupted MnP2 in the agenesis
      sample. This was a highly statistically significant difference (P < .001 and P <
      .0001, respectively) compared with the MnP2 inclinations in the control sample.
      The delay in dental age was significantly greater in patients with agenesis (2.1
      years) compared with the delay in the control group (1.5 years) (P < .001).
      CONCLUSION: Both null hypotheses are rejected. The results of this study
      statistically support the hypothesis that aplasia of MnP2, distally displaced
      MnP2s, and delayed tooth formation are part of a genetically related pattern of
      dental anomalies.

PMID- 23883309
TI  - Corrigendum.

PMID- 23883307
TI  - The role of speech-specific properties of the background in the irrelevant sound
      effect.
AB  - The irrelevant sound effect (ISE) is the finding that serial recall performance
      is impaired under complex auditory backgrounds such as speech as compared to
      white noise or silence. Several findings have demonstrated that ISE occurs with
      nonspeech backgrounds and that the changing-state complexity of the background
      stimuli is critical to ISE. In a pair of experiments, we investigate whether
      speech-like qualities of the irrelevant background have an effect beyond their
      changing-state complexity. We do so by using two kinds of transformations of
      speech with identical changing-state complexity: one kind that preserved speech
      like information (sinewave speech and fully reversed sinewave speech) and others
      in which this information was distorted (two selectively reversed sinewave speech
      conditions). Our results indicate that even when changing-state complexity is
      held constant, sinewave speech conditions in which speech-like interformant
      relationships are disrupted, produce less ISE than those in which these
      relationships are preserved. This indicates that speech-like properties of the
      background are important beyond their changing-state complexity for ISE. 

PMID- 23883310
TI  - Static liquid permeation cell method for determining the migration parameters of
      low molecular weight organic compounds in polyethylene terephthalate.
AB  - The migration of low molecular weight organic compounds through polyethylene
      terephthalate (PET) films was determined by using a custom permeation cell
      assembly. Fatty food simulant (Miglyol 812) was added to the receptor chamber,
      while the donor chamber was filled with 1% and 10% (v/v) migrant compounds spiked
      in simulant. The permeation cell was maintained at 40 degrees C, 66 degrees C,
      100 degrees C or 121 degrees C for up to 25 days of polymer film exposure time.
      Migrants in Miglyol were directly quantified without a liquid-liquid extraction
      step by headspace-GC-MS analysis. Experimental diffusion coefficients (DP) of
      toluene, benzyl alcohol, ethyl butyrate and methyl salicylate through PET film
      were determined. Results from Limm's diffusion model showed that the predicted DP
      values for PET were all greater than the experimental values. DP values predicted
      by Piringer's diffusion model were also greater than those determined
      experimentally at 66 degrees C, 100 degrees C and 121 degrees C. However,
      Piringer's model led to the underestimation of benzyl alcohol (Ap = 3.7) and
      methyl salicylate (Ap = 4.0) diffusion at 40 degrees C with its revised "upper
      bound" Ap value of 3.1 at temperatures below the glass transition temperature
      (Tg) of PET (<70 degrees C). This implies that input parameters of Piringer's
      model may need to be revised to ensure a margin of safety for consumers. On the
      other hand, at temperatures greater than the Tg, both models appear too
      conservative and unrealistic. The highest estimated Ap value from Piringer's
      model was 2.6 for methyl salicylate, which was much lower than the "upper-bound"
      Ap value of 6.4 for PET. Therefore, it may be necessary further to refine "upper
      bound" Ap values for PET such that Piringer's model does not significantly
      underestimate or overestimate the migration of organic compounds dependent upon
      the temperature condition of the food contact material.

PMID- 23883311
TI  - Fast-dissolving sublingual films of terbutaline sulfate: formulation and in
      vitro/in vivo evaluation.
AB  - Terbutaline sulfate fast dissolving sublingual films were prepared using seven
      drug compatible film formers in different combinations and proportions. The film
      polymers are maltodextrin, Na alginate, Carpabol 430, xanthan gum, HPMC E5, PVP K
      25, and Na CMC. Propylene glycol and sorbitol were used as plasticizers and
      mannitol as filler. The optimum polymer concentrations and the plasticizer amount
      were selected on the basis of flexibility, tensile strength, and stickiness of
      the films. The prepared films were evaluated for their tensile strength,
      thickness uniformity, disintegration time (in vitro and in vivo), in vitro
      dissolution, and moisture content. Polymer type rather than total polymer
      concentration or plasticizer amount showed a significant effect on the tested
      film properties. A randomized, single dose, crossover study was conducted in four
      healthy volunteers to compare the pharmacokinetic profile of terbutaline sulfate
      from the prepared films and the conventional oral tablets. The film formula of
      choice gave a significantly faster drug absorption rate and recorded a relative
      bioavailability of 204.08%. Sublingual films could be promising as a convenient
      delivery system for terbutaline sulfate in patients with swallowing problems. The
      improved extent of absorption (higher AUC(0-24)) indicates success in improving
      drug bioavailability, and the faster absorption rate could be promising for the
      management of acute episodes of asthma. 

PMID- 23883312
TI  - Clinical course of sepsis, severe sepsis, and septic shock in a cohort of
      infected patients from ten Colombian hospitals.
AB  - BACKGROUND: Sepsis has several clinical stages, and mortality rates are different
      for each stage. Our goal was to establish the evolution and the determinants of
      the progression of clinical stages, from infection to septic shock, over the
      first week, as well as their relationship to 7-day and 28-day mortality. METHODS:
      This is a secondary analysis of a multicenter cohort of inpatients hospitalized
      in general wards or intensive care units (ICUs). The general estimating equations
      (GEE) model was used to estimate the risk of progression and the determinants of
      stages of infection over the first week. Cox regression with time-dependent
      covariates and fixed covariates was used to determine the factors related with 7
      day and 28-day mortality, respectively. RESULTS: In 2681 patients we show that
      progression to severe sepsis and septic shock increases with intraabdominal and
      respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21,
      95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and
      Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and
      Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores.
      The variables related with first-week mortality were progression to severe sepsis
      [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98],
      respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR =
      1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores.
      CONCLUSIONS: Intraabdominal and respiratory sources of infection, independently
      of SOFA and APACHE II scores, increase the risk of clinical progression to more
      severe stages of sepsis; and these factors, together with progression of the
      infection itself, are the main determinants of 7-day and 28-day mortality.

PMID- 23883313
TI  - A novel chiral bisphosphine-thiourea ligand for asymmetric hydrogenation of
      beta,beta-disubstituted nitroalkenes.
AB  - A novel chiral bisphosphine-thiourea ligand was developed and applied in the
      highly enantioselective hydrogenation of beta,beta-disubstituted nitroalkenes (up
      to 99% yield and 99% ee). With low catalytic loading (0.25 mol %), 98% ee and 98%
      conversion were obtained. The thiourea group takes on an important role in this
      catalytic system. 

PMID- 23883314
TI  - Electronic nose based on multipatterns of ZnO nanorods on a quartz resonator with
      remote electrodes.
AB  - An electrodeless monolithic multichannel quartz crystal microbalance (MQCM)
      sensor was developed via the direct growth of ZnO nanorod patterns of various
      sizes onto an electrodeless quartz crystal plate. The patterned ZnO nanorods
      acted as independent resonators with different frequencies upon exposure to an
      electric field. The added mass of ZnO nanostructures was found to significantly
      enhance the quality factor (QF) of the resonator in electrodeless QCM
      configuration. The QF increased with the length of the ZnO nanorods; ZnO nanorods
      5 MUm in length yielded a 7-fold higher QF compared to the QF of a quartz plate
      without ZnO nanorods. In addition, the ZnO nanorods offered enhanced sensitivity
      due to the enlarged sensing area. The developed sensor was used as an electronic
      nose for detection of vapor mixtures with impurities. 

PMID- 23883315
TI  - Prediction of structures and atomization energies of small silver clusters,
      (Ag)n, n < 100.
AB  - Neutral silver clusters, Ag(n), were studied using density functional theory
      (DFT) followed by high level coupled cluster CCSD(T) calculations to determine
      the low energy isomers for each cluster size for small clusters. The normalized
      atomization energy, heats of formation, and average bond lengths were calculated
      for each of the different isomeric forms of the silver clusters. For n = 2-6, the
      preferred geometry is planar, and the larger n = 7-8 clusters prefer higher
      symmetry, three-dimensional geometries. The low spin state is predicted to be the
      ground state for every cluster size. A number of new low energy isomers for the
      heptamer and octamer were found. Additional larger Ag(n) structures, n < 100,
      were initially optimized using a tree growth-hybrid genetic algorithm with an
      embedded atom method (EAM) potential. For n <= 20, DFT was used to optimize the
      geometries. DFT with benchmarked functionals were used to predict that the
      normalized atomization energies ((AE)s) for Ag(n) start to converge slowly to the
      bulk at n = 55. The (AE) for Ag99 is predicted to be ~50 kcal/mol.

PMID- 23883316
TI  - Supersensitive detection of chlorinated phenols by multiple amplification
      electrochemiluminescence sensing based on carbon quantum dots/graphene.
AB  - A novel electrochemiluminescence (ECL) sensor based on carbon quantum dots (CQDs)
      immobilized on graphene (GR) has been first developed for the determination of
      chlorinated phenols (CPs) in water. The detection is based on the ECL signals
      from the interaction between the analytes and the excited CQDs (C(*+)) using
      S2O8(2-) as coreactant. GR facilitates both C(*-) and SO4(*-) production,
      resulting in a high yield of C(*+), and the multistage amplification effect leads
      to a nearly 48-fold ECL amplification. Pentachlorophenol (PCP) is often monitored
      as an important indicator for CPs in real environmental samples, but its
      ultratrace and real-time analysis is an intractable issue in environmental
      monitoring. The resulting ECL sensor enables the real-time detection of PCP with
      unprecedented sensitivity reaching 1.0 * 10(-12) M concentration in a wide linear
      range from 1.0 * 10(-12) to 1.0 * 10(-8) M. The ECL sensor showed high
      selectivity to CPs, especially to PCP. The practicability of the sensing platform
      in real water samples showed ideal recovery rates. It is envisaged that the eco
      friendly and recyclable sensor could be employed in the identification of key CPs
      in the environment. 

PMID- 23883317
TI  - Diel leaf growth of soybean: a novel method to analyze two-dimensional leaf
      expansion in high temporal resolution based on a marker tracking approach
      (Martrack Leaf).
AB  - BACKGROUND: We present a novel method for quantitative analysis of dicot leaf
      expansion at high temporal resolution. Image sequences of growing leaves were
      assessed using a marker tracking algorithm. An important feature of the method is
      the attachment of dark beads that serve as artificial landmarks to the leaf
      margin. The beads are mechanically constricted to the focal plane of a camera.
      Leaf expansion is approximated by the increase in area of the polygon defined by
      the centers of mass of the beads surrounding the leaf. Fluctuating illumination
      conditions often pose serious problems for tracking natural structures of a leaf;
      this problem is circumvented here by the use of the beads. RESULTS: The new
      method has been used to assess leaf growth in environmental situations with
      different illumination conditions that are typical in agricultural and biological
      experiments: Constant illumination via fluorescent light tubes in a climate
      chamber, a mix of natural and artificial illumination in a greenhouse and natural
      illumination of the situation on typical summer days in the field. Typical
      features of diel (24h) soybean leaf growth patterns were revealed in all three
      conditions, thereby demonstrating the general applicability of the method.
      Algorithms are provided to the entire community interested in using such
      approaches. CONCLUSIONS: The implementation Martrack Leaf presented here is a
      robust method to investigate diel leaf growth rhythms both under natural and
      artificial illumination conditions. It will be beneficial for the further
      elucidation of genotype x environment x management interactions affecting leaf
      growth processes.

PMID- 23883318
TI  - Laboratory intercomparison on the gamma-H2AX foci assay.
AB  - The focus of the study is an intercomparison of laboratories' dose-assessment
      performances using the gamma-H2AX foci assay as a diagnostic triage tool for
      rapid individual radiation dose assessment. Homogenously X-irradiated (240 kVp, 1
      Gy/min) blood samples for establishing calibration data (0.25-4 Gy) as well as
      blinded test samples (0.1-6.4 Gy) were incubated at 37 degrees C for 2 and 24 h
      (repair time) and sent to the participants. The foci assay was performed
      according to protocols individually established in participating laboratories and
      therefore varied. The time taken to report dose estimates was documented for each
      laboratory. Additional information concerning laboratory
      organization/characteristics as well as assay performance was collected. The mean
      absolute difference (MAD) of estimated doses relative to the actual doses was
      calculated and radiation doses were merged into four triage categories reflecting
      clinical relevance to calculate accuracy, sensitivity and specificity. First
      gamma-H2AX based dose estimates were reported 7 h after sample receipt. Estimates
      were similarly accurate for 2 and 24 h repair times, providing scope for its use
      in the early phase of a radiation exposure incident. Equal accuracy was achieved
      by scoring 20, 30, 40 or 50 cells per sample. However, MAD values of 0.5-0.7 Gy
      and 1.3-1.7 Gy divided the data sets into two groups, driven mainly by the
      considerable differences in foci yields between calibration and blind samples.
      Foci yields also varied dramatically between laboratories, highlighting
      reproducibility issues as an important caveat of the foci assay. Nonetheless,
      foci counts could distinguish high- and low-dose samples in all data sets and
      binary dose categories of clinical significance could be discriminated with
      satisfactory accuracy (mean 84%, +/-0.03 SEM). Overall, the results suggest that
      the gamma-H2AX assay is a useful tool for rapidly screening individuals for
      significant exposures that occurred up to at least 24 h earlier, and may help to
      prioritize cytogenetic dosimetry follow-up. 

PMID- 23883319
TI  - Effects of solar particle event proton radiation on parameters related to ferret
      emesis.
AB  - The effectiveness of simulated solar particle event (SPE) proton radiation to
      induce retching and vomiting was evaluated in the ferret experimental animal
      model. The endpoints measured in the study included: (1) the fraction of animals
      that retched or vomited, (2) the number of retches or vomits observed, (3) the
      latency period before the first retch or vomit and (4) the duration between the
      first and last retching or vomiting events. The results demonstrated that gamma
      ray and proton irradiation delivered at a high dose rate of 0.5 Gy/min induced
      dose-dependent changes in the endpoints related to retching and vomiting. The
      minimum radiation doses required to induce statistically significant changes in
      retching- and vomiting-related endpoints were 0.75 and 1.0 Gy, respectively, and
      the relative biological effectiveness (RBE) of proton radiation at the high dose
      rate did not significantly differ from 1. Similar but less consistent and smaller
      changes in the retching- and vomiting-related endpoints were observed for groups
      irradiated with gamma rays and protons delivered at a low dose rate of 0.5 Gy/h.
      Since this low dose rate is similar to a radiation dose rate expected during a
      SPE, these results suggest that the risk of SPE radiation-induced vomiting is low
      and may reach statistical significance only when the radiation dose reaches 1 Gy
      or higher. 

PMID- 23883321
TI  - What experienced HIV-infected lay peer educators working in Midwestern U.S. HIV
      medical care settings think about their role and contributions to patient care.
AB  - This qualitative study examined the role of experienced HIV-infected lay
      individuals who work in HIV medical care settings as educators. Participants in
      this study had been in the role an average of 4 years, and referred to their work
      as "peering," a newly coined verb in the vein of nursing. An overarching theme
      was that the title "peer educator" captured neither the scope of their work, nor
      the skill set they contribute to patient care. Peers brought unique contributions
      to the HIV care team that were vital to encouraging patients to stay engaged in
      care. Peers felt undervalued and expressed the wish to be "professionalized."
      Results from this study suggest that peers show promise as behavior change agents
      who can model healthful behaviors, particularly for newly diagnosed patients or
      those struggling with engagement in HIV care and adherence to treatment. However,
      peers need and want more formal training in behavior change science, and peer-led
      services must become more uniform and readily available to patients across HIV
      care settings. Research is needed to document the positive impact that peers can
      have on HIV-related health outcomes and to increased knowledge about the
      attributes of successful peers.

PMID- 23883320
TI  - Counselor-based rapid HIV testing in community pharmacies.
AB  - The purpose of this study was to examine the results of implementing a rapid
      counselor-based HIV testing program in community pharmacies. A prospective cross
      sectional study was conducted on a convenience sample of clients at five
      community pharmacies in New York City (NYC). In 294 days of pharmacy testing,
      2805 clients were eligible to receive testing, and 2030 individuals agreed to
      test. The average age was 33+/-15 years, 41% were male, 59% were Hispanic, 77%
      had been previously tested for HIV, and 34% were uninsured. HIV incidence was
      0.3%, median CD4 cell count was 622.0, and the average age of the newly diagnosed
      positives was 36.0+/-13.9 years. Participants were satisfied with a counselor
      based rapid HIV testing program in community-based pharmacies.

PMID- 23883322
TI  - Homozygous EXOSC3 mutation c.92G->C, p.G31A is a founder mutation causing severe
      pontocerebellar hypoplasia type 1 among the Czech Roma.
AB  - Pontocerebellar hypoplasia type 1 (PCH1) is characterized by cerebellar and
      anterior horn motor neuron degeneration and loss, signs of spinal muscular
      atrophy plus. Patients manifest severe perinatal weakness, hypotonia, and
      respiratory insufficiency, causing death frequently before the age of 1 year.
      Recently, causative mutations in EXOSC3 were reported in a majority of PCH1
      patients, but the detailed clinical phenotype caused by EXOSC3 mutations,
      genotype-phenotype correlations, and prevalent mutations in specific ethnic
      groups is not yet known. Three unrelated Czech Roma patients with PCH1 were
      investigated clinically, electrophysiologically, neuroradiologically, and
      neuropathologically (patients 1 and 2). The entire coding region of the EXOSC3
      gene, including the adjacent intron sequences, was sequenced in all three
      patients. The same mutation c.92G->C, p.G31A in EXOSC3 was found in all three
      affected patients in homozygous state and in heterozygous state in the parents
      from two of the families. Haplotype analysis with four flanking microsatellite
      markers showed identical haplotype in 9 out of 11 haplotypes carrying the c.92G
      >C, p.G31A mutation. Furthermore, four heterozygotes for this mutation were found
      in anonymous DNA samples from 90 unrelated Roma individuals. All four of these
      samples shared the same haplotype. No heterozygous sample was found among 120
      anonymous DNA samples from Czech non-Roma individuals with no familial relation.
      It may therefore be concluded that EXOSC3 c.92G->C, p.G31A mutation is a founder
      mutation with high prevalence among the Czech Roma causing a similar and
      particularly severe phenotype of PCH1. These observations from the Czech Roma may
      have consequences also for other Roma from other countries. PCH1 caused by EXOSC3
      founder mutation c.92G->C, p.G31A extends the list of autosomal recessive
      disorders rare among the general population but more frequent among Roma at least
      in the Czech Republic.

PMID- 23883323
TI  - Oxyazapeptides: synthesis, structure determination, and conformational analysis.
AB  - Herein we report the synthesis, X-ray structure determination, and conformational
      analysis of a novel class of heteroatom-modified peptidomimetics, which we shall
      call "oxyazapeptides". Substituting the typical native N-C(alpha) bond with an O
      N(alpha) bond creates a completely new, previously unknown family of
      peptidomimetics, which are hydrolytically stable and display very interesting
      conformational behavior. Force field calculations revealed that the barrier to
      rotation around the O-N(alpha) bond in oxyazapeptides is five times lower than
      that around the N-N(alpha) bond in azapeptides. Also, conformational analysis
      supported by X-ray suggests that the oxyaza moiety can effectively induce beta
      turns, which can make the newly discovered oxyazapeptide scaffold a useful tool
      for drug discovery and for design of biologics. 

PMID- 23883325
TI  - Diradicals.

PMID- 23883324
TI  - Body mass index, occupational activity, and leisure-time physical activity: an
      exploration of risk factors and modifiers for knee osteoarthritis in the 1946
      British birth cohort.
AB  - BACKGROUND: Knee osteoarthritis (kOA) risk is increased by obesity and physical
      activities (PA) which mechanically stress the joint. We examined the associations
      of midlife kOA with body mass index (BMI) and activity exposure across adult life
      and their interaction. METHODS: Data are from a UK birth cohort of 2597
      participants with a clinical assessment for kOA at age 53. At ages 36, 43 and 53
      BMI (kg/m2), self-reported leisure-time PA, and occupational activity
      (kneeling/squatting; lifting; climbing; sitting; assigned using a job-exposure
      matrix) were ascertained. Associations were explored using the multiplicative
      logistic model. RESULTS: BMI was strongly and positively associated with kOA in
      men and women. Men and women in manual occupations also had greater odds of kOA;
      there was a weak suggestion that kOA risk was higher among men exposed to lifting
      or kneeling at work. For men, the only evidence of a multiplicative interaction
      between BMI and activities was for lifting (p = 0.01) at age 43; BMI conferred
      higher kOA risk among those most-likely to lift at work (OR per increase in BMI z
      score: 3.55, 95% CI: 1.72-7.33). For women, the only evidence of an interaction
      was between BMI and leisure-time PA (p = 0.005) at age 43; BMI conferred higher
      kOA risk among those at higher PA levels (OR per increase in BMI z-score: 1.59,
      95% CI: 1.26-2.00 in inactive; 1.70, 95% CI: 1.14-2.55 (less-active); and 4.44;
      95% CI: 2.26-8.36 (most-active). CONCLUSIONS: At the very least, our study
      suggests that more active individuals (at work and in leisure) may see a greater
      reduction in risk of kOA from avoiding a high BMI than those less active.

PMID- 23883326
TI  - Health-related quality of life in long-term survivors after renal cancer
      treatment.
AB  - OBJECTIVE: The most important outcome of renal cell carcinoma (RCC) treatment is
      survival. However, all cancer treatment should evaluate the health-related
      quality of life (HRQoL) outcome of the treatment. This has not been sufficiently
      documented in RCC. The aim of this investigation was therefore to document the
      HRQoL outcome of RCC. MATERIAL AND METHODS: All 413 RCC patients treated with
      radical or partial nephrectomy at Haukeland University Hospital, Norway, during
      the period 1997--2010 were included. After exclusions, invitations to participate
      were mailed to 260 patients; 185 patients (71%) returned the questionnaires. In
      addition, a cohort of general head and neck squamous cell carcinoma (HNSCC)
      patients, a cohort of laryngectomized HNSCC patients, and a cohort from the
      general population of Norway, were used to compare the RCC patients' HRQoL
      scores. RESULTS: Performance status as measured by the American Society of
      Anesthesiologists (ASA) score and Eastern Cooperative Oncology Group (ECOG)
      classification at diagnosis showed an inverse relation to HRQoL [maximum
      coefficient of variation (CVmax) = 5.3%, p < 0.05]. Flank and open transabdominal
      approaches to RCC tumour resection were followed by reduced HRQoL compared with a
      general cohort of Norwegian citizens. However, the laparoscopically treated RCC
      patients had HRQoL scores at the level of the population. The indices "general
      health/QoL", the functional indices, and the symptom indices "fatigue", "pain",
      "sleep", "nausea and vomiting", "constipation" and "diarrhoea" were particularly
      affected. CONCLUSION: The results show that RCC patients, and in particular those
      treated by a flank approach but not those treated by minimal invasive surgery,
      have a multifacetedly reduced HRQoL compared to a general population cohort.

PMID- 23883327
TI  - Identification of G protein-coupled receptor signaling pathway proteins in marine
      diatoms using comparative genomics.
AB  - BACKGROUND: The G protein-coupled receptor (GPCR) signaling pathway plays an
      essential role in signal transmission and response to external stimuli in
      mammalian cells. Protein components of this pathway have been characterized in
      plants and simpler eukaryotes such as yeast, but their presence and role in
      unicellular photosynthetic eukaryotes have not been determined. We use a
      comparative genomics approach using whole genome sequences and gene expression
      libraries of four diatoms (Pseudo-nitzschia multiseries, Thalassiosira
      pseudonana, Phaeodactylum tricornutum and Fragilariopsis cylindrus) to search for
      evidence of GPCR signaling pathway proteins that share sequence conservation to
      known GPCR pathway proteins. RESULTS: The majority of the core components of GPCR
      signaling were well conserved in all four diatoms, with protein sequence
      similarity to GPCRs, human G protein alpha- and beta-subunits and downstream
      effectors. There was evidence for the Ggamma-subunit and thus a full
      heterotrimeric G protein only in T. pseudonana. Phylogenetic analysis of putative
      diatom GPCRs indicated similarity but deep divergence to the class C GPCRs, with
      branches basal to the GABAB receptor subfamily. The extracellular and
      intracellular regions of these putative diatom GPCR sequences exhibited large
      variation in sequence length, and seven of these sequences contained the
      necessary ligand binding domain for class C GPCR activation. Transcriptional data
      indicated that a number of the putative GPCR sequences are expressed in diatoms
      under various stress conditions in culture, and that many of the GPCR-activated
      signaling proteins, including the G protein, are also expressed. CONCLUSIONS: The
      presence of sequences in all four diatoms that code for the proteins required for
      a functional mammalian GPCR pathway highlights the highly conserved nature of
      this pathway and suggests a complex signaling machinery related to environmental
      perception and response in these unicellular organisms. The lack of evidence for
      some GPCR pathway proteins in one or more of the diatoms, such as the Ggamma
      subunit, may be due to differences in genome completeness and genome coverage for
      the four diatoms. The high divergence of putative diatom GPCR sequences to known
      class C GPCRs suggests these sequences may represent another, potentially
      ancestral, subfamily of class C GPCRs.

PMID- 23883328
TI  - Chiral colloidal molecules and observation of the propeller effect.
AB  - Chiral molecules play an important role in biological and chemical processes, but
      physical effects due to their symmetry-breaking are generally weak. Several
      physical chiral separation schemes which could potentially be useful, including
      the propeller effect, have therefore not yet been demonstrated at the molecular
      scale. However, it has been proposed that complex nonspherical colloidal
      particles could act as "colloidal molecules" in mesoscopic model systems to
      permit the visualization of molecular phenomena that are otherwise difficult to
      observe. Unfortunately, it is difficult to synthesize such colloids because
      surface minimization generally favors the growth of symmetric particles. Here we
      demonstrate the production of large numbers of complex colloids with glancing
      angle physical vapor deposition. We use chiral colloids to demonstrate the
      Baranova and Zel'dovich (Baranova, N. B.; and Zel'dovich, B. Y. Chem. Phys. Lett.
      1978, 57, 435) propeller effect: the separation of a racemic mixture by
      application of a rotating field that couples to the dipole moment of the
      enantiomers and screw propels them in opposite directions. The handedness of the
      colloidal suspensions is monitored with circular differential light scattering.
      An exact solution for the colloid's propulsion is derived, and comparisons
      between the colloidal system and the corresponding effect at the molecular scale
      are made.

PMID- 23883329
TI  - Effects of aggregate structure on the dissolution kinetics of citrate-stabilized
      silver nanoparticles.
AB  - Aggregation and dissolution kinetics are important environmental properties of
      silver nanoparticles (AgNPs), and characterization of the interplay between these
      two processes is critical to understanding the environmental fate, transport, and
      biological impacts of AgNPs. Time-resolved dynamic light scattering was employed
      to measure the aggregation kinetics of AgNPs over a range of monovalent
      electrolyte (NaCl) concentrations. The fractal dimensions (Df) obtained from
      aggregation kinetics and static light scattering were found to be dependent on
      the aggregation mechanism and, in accord with expectation, varied from 1.7 for
      diffusion-limited cluster aggregation to 2.3 for reaction-limited cluster
      aggregation. An aggregation-dissolution model, in which the proportion of
      accessible reactive sites on primary particles as well as the aggregate size and
      Df are assumed to be key determinants of reactivity, is found to provide an
      excellent description of the decline of normalized rate of dissolution of AgNPs
      during aggregation for different NaCl concentrations. This model also provides
      fundamental insights into the factors accounting for the observed change in rate
      of dissolution of AgNPs on injection into seawater thereby facilitating improved
      prediction of the likely toxicity of AgNPs in the marine environment. 

PMID- 23883330
TI  - Rationing lung transplants--procedural fairness in allocation and appeals.

PMID- 23883332
TI  - Holes in the safety net--legal immigrants' access to health insurance.

PMID- 23883331
TI  - Stuck between health and immigration reform--care for undocumented immigrants.

PMID- 23883333
TI  - Nondisclosure during psychotherapy supervision: validation of the German version
      of the supervisory questionnaire (SQ).
AB  - Nondisclosure is considered to be a central obstacle to effective psychotherapy
      supervision. The aim of the current study was the validation of the German
      version of the Supervisory Questionnaire (SQ; Yourman & Farber, 1996), a short
      measure for the assessment of supervisee nondisclosure. The investigation was
      based on a sample of 589 supervisees. Confirmatory factor analyses suggested a
      two-factor model of the SQ which included one factor describing nondisclosure
      regarding the patient (alpha=.74) and another describing nondisclosure regarding
      the supervisor (alpha=.71). The SQ demonstrated satisfactory convergent and
      discriminant validity. Additionally assessed supervisee characteristics accounted
      for 16% of the variance in nondisclosure. These results provide general support
      for the reliability and validity of the SQ in a large sample of supervisees.

PMID- 23883334
TI  - Irritant nail dermatitis of chemical depilatory product presenting with
      koilonychia.
AB  - Chemical hair removal products are available as creams, gels, powders, aerosols
      and roll-ons and all of these forms work in the same way by breaking chemical
      bonds between sulfur atoms in the protein. Currently, the common active
      ingredients of these products are calcium thioglycolate, potassium thioglycolate,
      arsenic and sulfur minerals. Sulfur and arsenic containing products are important
      toxic chemicals which are mainly used for removing hair in developing countries.
      Irritant contact dermatitis accounts for 80% of all contact dermatitis reactions
      which are often occupation-related. Toluene sulfonamide, formaldehyde resin,
      acrylates and ethylcyanoacrylate are the most common irritants. Irritant nail
      dermatitis with plants has been well defined with Lobelia richardii flower,
      Compositae family and garlic. Although allergic dermatitis, irritant dermatitis
      and irritant nail dermatitis have been well demonstrated with chemicals,
      koilonychia is unusual presentation of irritant dermatitis. Here we describe a
      case of nail irritant dermatitis due to application of chemical depilatory
      product for hair removal presented with koilonychias. To our knowledge this is
      the first case of such presentation with koilonychia in the English literature.

PMID- 23883335
TI  - Langer mesomelic dysplasia in early fetuses: two cases and a literature review.
AB  - In the article, we report the autoptic, histological and radiographic phenotype
      of two fetuses (22 and 12 weeks) with Langer mesomelic dysplasia, a homozygous
      deletion of the 3' enhancer of the SHOX gene, and consanguineous parents affected
      by Leri-Weill dyschondrosteosis, performing a literature review of the primary
      forms of mesomelic dysplasia. A proper identification of the type of mesomelic
      dysplasia is important for genetic and reproductive counseling, estimation of
      child growth and prevention and/or treatment of complications. A competent
      pathologist could provide important diagnostic information, orienting or
      confirming the echographic or genetic suspect, sometimes suggesting diagnostic
      hypothesis concerning parental unidentified congenital syndromes. 

PMID- 23883336
TI  - Idiopathic arterial calcification of infancy-- peritoneal dialysis for treatment
      of hypertension.
AB  - Idiopathic infantile arterial calcification (IIAC) is a rare autosomal recessive
      disease usually diagnosed postmortem. The clinical presentation is not typical,
      but usually implies refractory hypertension and cardiorespiratory failure. We
      present a case of a newborn with IIAC who had fetal hydrops and refractory
      hypertension which normalized soon after initialization of peritoneal dialysis.
      With this case report, we wanted to highlight that peritoneal dialysis may be
      beneficial an effective therapeutic option for patients with IIAC and severe
      refractory hypertension. Until now, peritoneal dialysis was never performed in
      the treatment of patients with IIAC. 

PMID- 23883338
TI  - Tribute to Prof. John C. Wright.

PMID- 23883337
TI  - Severe eosinophilic pneumonia presenting during gemcitabine adjuvant
      chemotherapy.
AB  - Gemcitabine is widely accepted as the standard treatment for pancreatic cancer,
      but it can cause unpredictable side effects. Acute respiratory distress syndrome
      is a rare complication with gemcitabine, but is sometimes fatal. We describe a
      cured case of acute, severe gemcitabine-induced pulmonary toxicity. The patient
      was a 76-year-old man with pancreatic cancer who was receiving adjuvant
      gemcitabine chemotherapy after surgery. The patient received gemcitabine 1,000
      mg/m2 on days 1, 8, and 15 for three 4-week cycles, with intervals of 1 week. He
      developed severe general fatigue on day 1 of the third cycle. Computed tomography
      showed diffuse ground-glass opacity with pleural effusion. There was no increase
      in beta-D-glucan, and cytomegalovirus antigenemia assays were negative. No
      bacteria or acid-fast bacilli were found. The number of eosinophils in
      bronchoalveolar lavage fluid was increased. Considering these data, we diagnosed
      eosinophilic pneumonia induced by gemcitabine. The patient was immediately
      treated with a steroid and neutrophil elastase inhibitor under respiratory
      supportive therapy. After 4 weeks, his pulmonary symptoms were markedly improved.
      Physicians should be cognizant of the possible association of serious pulmonary
      toxicity with gemcitabine treatment. A delay in diagnosis and treatment could
      lead to a fatal outcome. 

PMID- 23883339
TI  - Autobiography of Prof. John C. Wright.

PMID- 23883344
TI  - Molecular orientation of enzymes attached to surfaces through defined chemical
      linkages at the solid-liquid interface.
AB  - The immobilization of enzymes on solid supports is widely used in many
      applications, including biosensors, antifouling coatings, food packaging
      materials, and biofuel cells. Enzymes tend to lose their activity when in contact
      with a support surface, a phenomenon that has been attributed to unfavorable
      orientation and (partial) unfolding. In this work, specific immobilization of 6
      phospho-beta-galactosidase (beta-Gal) on a self-assembled monolayer (SAM)
      containing maleimide end groups and oligo(ethylene glycol) spacer segments was
      achieved through a unique cysteinyl residue. A systematic means to characterize
      the interfacial orientation of immobilized enzymes has been developed using a
      combination of sum frequency generation vibrational spectroscopy and attenuated
      total reflectance FTIR-spectroscopy. The possible orientations of the immobilized
      beta-Gal were determined and found to be well-correlated with the tested activity
      of beta-Gal. This study will impact the development of an increasingly wide range
      of devices that use surface-immobilized enzymes as integral components with
      improved functions, better sensitivity, enhanced stability, and longer shelf
      life. 

PMID- 23883345
TI  - Age-related differences in symptoms, diagnosis and prognosis of bacteremia.
AB  - BACKGROUND: Elderly patients are at particular risk for bacteremia and sepsis.
      Atypical presentation may complicate the diagnosis. We studied patients with
      bacteremia, in order to assess possible age-related effects on the clinical
      presentation and course of severe infections. METHODS: We reviewed the records of
      680 patients hospitalized between 1994 and 2004. All patients were diagnosed with
      bacteremia, 450 caused by Escherichia coli and 230 by Streptococcus pneumoniae.
      Descriptive analyses were performed for three age groups (< 65 years, 65-84
      years, >= 85 years). In multivariate analyses age was dichotomized (< 65, >= 65
      years). Symptoms were categorized into atypical or typical. Prognostic
      sensitivity of CRP and SIRS in identifying early organ failure was studied at
      different cut-off values. Outcome variables were organ failure within one day
      after admission and in-hospital mortality. RESULTS: The higher age-groups more
      often presented atypical symptoms (p <0.001), decline in general health
      (p=0.029), and higher in-hospital mortality (p<0.001). The prognostic sensitivity
      of CRP did not differ between age groups, but in those >= 85 years the prognostic
      sensitivity of two SIRS criteria was lower than that of three criteria. Classical
      symptoms were protective for early organ failure (OR 0.67, 95% CI 0.45-0.99), and
      risk factors included; age >= 65 years (OR 1.65, 95% CI 1.09-2.49), comorbid
      illnesses (OR 1.19, 95% CI 1.02-1.40 per diagnosis), decline in general health
      (OR 2.28, 95% CI 1.58-3.27), tachycardia (OR 1.50, 95% CI 1.02-2.20), tachypnea
      (OR 3.86, 95% CI 2.64-5.66), and leukopenia (OR 4.16, 95% CI 1.59-10.91). Fever
      was protective for in-hospital mortality (OR 0.46, 95% CI 0.24-0.89), and risk
      factors included; age >= 65 years (OR 15.02, 95% CI 3.68-61.29), >= 1 comorbid
      illness (OR 2.61, 95% CI 1.11-6.14), bacteremia caused by S. pneumoniae (OR 2.79,
      95% CI 1.43-5.46), leukopenia (OR 4.62, 95% CI 1.88-11.37), and number of early
      failing organs (OR 3.06, 95% CI 2.20-4.27 per failing organ). CONCLUSIONS:
      Elderly patients with bacteremia more often present with atypical symptoms and
      reduced general health. The SIRS-criteria have poorer sensitivity for identifying
      organ failure in these patients. Advanced age, comorbidity, decline in general
      health, pneumococcal infection, and absence of classical symptoms are markers of
      a poor prognosis.

PMID- 23883346
TI  - The effectiveness of scoliosis screening programs: methods for systematic review
      and expert panel recommendations formulation.
AB  - BACKGROUND: Literature on scoliosis screening is vast, however because of the
      observational nature of available data and methodological flaws, data
      interpretation is often complex, leading to incomplete and sometimes, somewhat
      misleading conclusions. The need to propose a set of methods for critical
      appraisal of the literature about scoliosis screening, a comprehensive summary
      and rating of the available evidence appeared essential. METHODS: To address
      these gaps, the study aims were: i) To propose a framework for the assessment of
      published studies on scoliosis screening effectiveness; ii) To suggest specific
      questions to be answered on screening effectiveness instead of trying to reach a
      global position for or against the programs; iii) To contextualize the knowledge
      through expert panel consultation and meaningful recommendations. The general
      methodological approach proceeds through the following steps: Elaboration of the
      conceptual framework; Formulation of the review questions; Identification of the
      criteria for the review; Selection of the studies; Critical assessment of the
      studies; Results synthesis; Formulation and grading of recommendations in
      response to the questions. This plan follows at best GRADE Group (Grades of
      Recommendation, Assessment, Development and Evaluation) requirements for
      systematic reviews, assessing quality of evidence and grading the strength of
      recommendations. CONCLUSIONS: In this article, the methods developed in support
      of this work are presented since they may be of some interest for similar reviews
      in scoliosis and orthopaedic fields.

PMID- 23883342
TI  - PDE4 as a target for cognition enhancement.
AB  - INTRODUCTION: The second messengers cAMP and cGMP mediate fundamental aspects of
      brain function relevant to memory, learning, and cognitive functions.
      Consequently, cyclic nucleotide phosphodiesterases (PDEs), the enzymes that
      inactivate the cyclic nucleotides, are promising targets for the development of
      cognition-enhancing drugs. AREAS COVERED: PDE4 is the largest of the 11 mammalian
      PDE families. This review covers the properties and functions of the PDE4 family,
      highlighting procognitive and memory-enhancing effects associated with their
      inactivation. EXPERT OPINION: PAN-selective PDE4 inhibitors exert a number of
      memory- and cognition-enhancing effects and have neuroprotective and
      neuroregenerative properties in preclinical models. The major hurdle for their
      clinical application is to target inhibitors to specific PDE4 isoforms relevant
      to particular cognitive disorders to realize the therapeutic potential while
      avoiding side effects, in particular emesis and nausea. The PDE4 family comprises
      four genes, PDE4A-D, each expressed as multiple variants. Progress to date stems
      from characterization of rodent models with selective ablation of individual PDE4
      subtypes, revealing that individual subtypes exert unique and non-redundant
      functions in the brain. Thus, targeting specific PDE4 subtypes, as well as
      splicing variants or conformational states, represents a promising strategy to
      separate the therapeutic benefits from the side effects of PAN-PDE4 inhibitors.

PMID- 23883347
TI  - Understanding energy-level alignment in donor-acceptor/metal interfaces from core
      level shifts.
AB  - The molecule/metal interface is the key element in charge injection devices. It
      can be generally defined by a monolayer-thick blend of donor and/or acceptor
      molecules in contact with a metal surface. Energy barriers for electron and hole
      injection are determined by the offset from HOMO (highest occupied) and LUMO
      (lowest unoccupied) molecular levels of this contact layer with respect to the
      Fermi level of the metal electrode. However, the HOMO and LUMO alignment is not
      easy to elucidate in complex multicomponent, molecule/metal systems. We
      demonstrate that core-level photoemission from donor-acceptor/metal interfaces
      can be used to straightforwardly and transparently assess molecular-level
      alignment. Systematic experiments in a variety of systems show characteristic
      binding energy shifts in core levels as a function of molecular donor/acceptor
      ratio, irrespective of the molecule or the metal. Such shifts reveal how the
      level alignment at the molecule/metal interface varies as a function of the donor
      acceptor stoichiometry in the contact blend. 

PMID- 23883348
TI  - Ruthenium-catalyzed regioselective C-H alkenylation directed by a free amino
      group.
AB  - The ruthenium-catalyzed alkenylation reactions of 2-aminobiphenyls and cumylamine
      proceed smoothly to produce the corresponding regioselectively alkenylated
      products. These reactions involve a C-H bond cleavage directed by their free
      amino groups. 

PMID- 23883349
TI  - Particled Mica, STB-HO has chemopreventive potential via G1 arrest, and
      inhibition of proliferation and vascular endothelial growth factor receptor 2 in
      HCT colorectal cancer cells.
AB  - BACKGROUND: Though Mica, a thin and sheet like mineral, has been used as a
      mineral medicine for treatment of bleeding, dysentery and inflammation in
      traditional medicine including Ayurveda, the biological evidences of Mica were
      not clearly elucidated so far. Thus, in the present study, the antitumor
      mechanism of particled Mica (STB-HO) was examined in colorectal cancers. METHODS:
      Athymic nude mice were inoculated with HCT116 colon cancer cells and orally
      administered STB-HO daily for 41 days, and HCT116 and human umbilical vein
      endothelial cells (HUVECs) were treated with STB-HO for 0 ~ 24 hours to perform
      immunoblotting, cytotoxicity assay, FACs analysis and measurement of matrix
      metalloproteinase 9 (MMP-9) secretion and other experiments. Significant
      differences of all date were evaluated using Student's t-test and a Turkey-Kramer
      multiple-comparison post test. RESULTS: STB-HO significantly suppressed the tumor
      volume and weight in athymic nude mice inoculated with HCT116 cells at a dose of
      100 mg/kg. Thus, the in vivo antitumor mechanism of STB-HO was to elucidated in
      vitro as well. STB-HO exerted cytotoxicity in HCT116, SW620 and HCT15 colorectal
      cancer cells. Also, STB-HO increased G1 cell population in a time and
      concentration dependent manner, enhanced the expression of p21, p27, p53 as
      cyclin dependent kinase (CDK) inhibitors, attenuated the expression of
      proliferating cell nuclear antigen (PCNA) and cyclin D1 and also reduced the
      production of vascular endothelial growth factor (VEGF) and matrix
      metalloproteinase 9 (MMP-9) in HCT116 cells. Consistently, STB-HO suppressed the
      phosphorylation of VEGFR2 in HCT116, SW620 and HCT15 cells. Also, STB-HO
      inhibited the VEGF mediated proliferation and also attenuated the phosphorylation
      of VEGFR2 and Akt in human umbilical vein endothelial cells (HUVECs).
      CONCLUSIONS: Collectively, these findings suggest that STB-HO has chemopreventive
      potential via G1 arrest and inhibition of proliferation and VEGFR2 in HCT116
      colorectal cancer cells.

PMID- 23883351
TI  - Maximum tumor diameter is not an accurate predictor of renal cell carcinoma tumor
      volume.
AB  - OBJECTIVE: The aim of this study was determine whether maximal renal cell
      carcinoma (RCC) size can be used to accurately determine tumor volume. MATERIAL
      AND METHODS: Following institutional review board approval, the study evaluated
      2180 patients who had been surgically treated for clear-cell RCC between 1985 and
      2006 who had data available on three tumor dimensions. Tumor volume (TV) was
      defined as (pi/6 * Height * Length * Width). True tumor volume (TTV) was
      calculated using the three measurements from the pathology report in the volume
      formula above. Estimated tumor volume (ETV) was calculated using only the largest
      dimension utilizing the same formula. RESULTS: Only 45 out of 2180 patients (2%)
      had equal values for all three tumor dimensions. The mean differences in ETV and
      TTV were 5.4 cm3 for pT1a tumors, 38 cm3 for pT1b tumors, 158 cm3 for pT2a
      tumors, 723 cm3 for pT2b tumors, 305 cm3 for pT3 tumors and 583 cm3 for pT4
      tumors (p < 0.001 for all). CONCLUSIONS: An ETV based on maximal tumor size is a
      poor assessment of TTV among patients with RCC, which is more pronounced with
      larger tumors. Future efforts to incorporate information on tumor volume in
      prognostic algorithms should use TTV.

PMID- 23883352
TI  - Atmospheric aerosol water-soluble organic carbon measurement: a theoretical
      analysis.
AB  - The measurement of Water-Soluble Organic Carbon (WSOC) in atmospheric aerosol is
      usually carried out by sample collection on filters, extraction in ultrapure
      water, filtration, and measurement of the total organic carbon. This paper
      investigates the role of different conditions of sampling and extraction as well
      as the range of solubilities of the organic compounds that contribute to the
      WSOC. The sampling and extraction of WSOC can be described by a single parameter,
      P, expressing the ratio of water used per volume of air sampled on the analyzed
      filter. Two cases are examined in order to bound the range of interactions of the
      various organic aerosol components with each other. In the first we assume that
      the organic species form an ideal solution in the particle and in the second that
      the extraction of a single compound is independent of the presence of the other
      organics. The ideal organic solution model predicts that species with water
      solubility as low as 10(-4) g L(-1) contribute to the measured WSOC. In the other
      end, the independent compounds model predicts that low-solubility (as low as 10(
      7) g L(-1)) compounds are part of the WSOC. Studies of the WSOC composition are
      consistent with the predictions of the ideal organic solution model. A value of P
      = 0.1 cm(3) m(-3) is proposed for the extraction of WSOC for typical organic
      aerosol concentrations (1-10 MUg m(-3)). WSOC measurements under high
      concentration conditions often used during source sampling will tend to give low
      WSOC values unless higher P values are used. 

PMID- 23883350
TI  - Association between the luteinizing hormone/chorionic gonadotropin receptor
      (LHCGR) rs4073366 polymorphism and ovarian hyperstimulation syndrome during
      controlled ovarian hyperstimulation.
AB  - BACKGROUND: The aim of this study was to determine the relationship between a
      purported luteinizing hormone/chorionic gonadotropin (LHCGR) high function
      polymorphism (rs4539842/insLQ) and outcome to controlled ovarian hyperstimulation
      (COH). METHODS: This was a prospective study of 172 patients undergoing COH at
      the Fertility and IVF Center at GWU. DNA was isolated from blood samples and a
      region encompassing the insLQ polymorphism was sequenced. We also investigated a
      polymorphism (rs4073366 G > C) that was 142 bp from insLQ. The association of the
      insLQ and rs4073366 alleles and outcome to COH (number of mature follicles,
      estradiol level on day of human chorionic gonadotropin (hCG) administration, the
      number of eggs retrieved and ovarian hyperstimulation syndrome (OHSS)) was
      determined. RESULTS: Increasing age and higher day 3 (basal) FSH levels were
      significantly associated with poorer response to COH. We found that both insLQ
      and rs4073366 were in linkage disequilibrium (LD) and no patients were homozygous
      for both recessive alleles (insLQ/insLQ; C/C). The insLQ variant was not
      significantly associated with any of the main outcomes to COH. Carrier status for
      the rs4073366 C variant was associated (P = 0.033) with an increased risk (OR
      2.95, 95% CI = 1.09-7.96) of developing OHSS. CONCLUSIONS: While age and day 3
      FSH levels were predictive of outcome, we found no association between insLQ and
      patient response to COH. Interestingly, rs4073366 C variant carrier status was
      associated with OHSS risk. To the best of our knowledge, this is the first report
      suggesting that LHCGR genetic variation might function in patient risk for OHSS.

PMID- 23883353
TI  - Automated method for simultaneous lead and strontium isotopic analysis applied to
      rainwater samples and airborne particulate filters (PM10).
AB  - A new automated, sensitive, and fast system for the simultaneous online isolation
      and preconcentration of lead and strontium by sorption on a microcolumn packed
      with Sr-resin using an inductively coupled plasma mass spectrometry (ICP-MS)
      detector was developed, hyphenating lab-on-valve (LOV) and multisyringe flow
      injection analysis (MSFIA). Pb and Sr are directly retained on the sorbent column
      and eluted with a solution of 0.05 mol L(-1) ammonium oxalate. The detection
      limits achieved were 0.04 ng for lead and 0.03 ng for strontium. Mass calibration
      curves were used since the proposed system allows the use of different sample
      volumes for preconcentration. Mass linear working ranges were between 0.13 and 50
      ng and 0.1 and 50 ng for lead and strontium, respectively. The repeatability of
      the method, expressed as RSD, was 2.1% and 2.7% for Pb and Sr, respectively.
      Environmental samples such as rainwater and airborne particulate (PM10) filters
      as well as a certified reference material SLRS-4 (river water) were
      satisfactorily analyzed obtaining recoveries between 90 and 110% for both
      elements. The main features of the LOV-MSFIA-ICP-MS system proposed are the
      capability to renew solid phase extraction at will in a fully automated way, the
      remarkable stability of the column which can be reused up to 160 times, and the
      potential to perform isotopic analysis. 

PMID- 23883355
TI  - Salmonellae in fish feces analyzed by in situ hybridization and quantitative
      polymerase chain reaction.
AB  - The potential of fish to transfer salmonellae from heterogeneous aquatic biofilms
      into feces was assessed in controlled aquarium studies with Suckermouth Catfish
      Hypostomus plecostomus and with biofilms inoculated with salmonellae. Neither the
      presence of catfish nor inoculation with salmonellae had detectable effects on
      the abundance of the microbial community. Densities of the microbial community
      were about 10(5) cells/mL in the water during a 1-week period, whereas densities
      of the microbial community increased 10-fold (10(6) to 10(7) cells/mg) in catfish
      feces during the same period. Salmonellae were detected by both quantitative
      polymerase chain reaction (qPCR) and situ hybridization in water samples
      immediately after inoculation, in numbers of about 10(4) cells/mL, representing
      up to 20% of the cells of the microbial community. Numbers decreased by three
      orders of magnitude within the first 3 d of the study, which represented only
      0.01% of the community, and became undetectable after day 5. In catfish feces,
      numbers of Salmonella initially increased to up to 6% of the cells of the
      community but then declined. These results suggest that Salmonella are not
      biomagnified during gut passage, and thus, fish only provide a means for the
      translocation of this pathogen.

PMID- 23883356
TI  - Parent report and electronic medical record agreement on asthma education
      provided and children's tobacco smoke exposure.
AB  - OBJECTIVE: To examine the concordance between parent report and electronic
      medical record documentation of asthma health education provided during a single
      clinic visit and second-hand tobacco smoke exposure among children with asthma.
      METHODS: Parents of children with asthma were recruited from two types of clinics
      using different electronic medical record systems: asthma-specialty or general
      pediatric health department clinics. After their child's outpatient visit,
      parents were interviewed by trained study staff. Interview data were compared to
      electronic medical records for agreement in five categories of asthma health
      education and for the child's environmental tobacco smoke exposure. Kappa
      statistics were used to identify strength of agreement. Chi square and t-tests
      were used to examine differences between clinic types. RESULTS: Of 255 parents
      participating in the study 90.6% were African American and 96.1% were female.
      Agreement was poor across all clinics but was higher within the asthma specialty
      clinics than the health department clinics for smoke exposure (kappa = 0.410
      versus 0.205), asthma diagnosis/disease process (kappa = 0.213 versus -0.016) and
      devices reviewed (kappa = 0.253 versus -0.089) with parents generally reporting
      more education provided. For the 203 children with complete medical records,
      40.5% did not have any documentation regarding smoking exposure in the home and
      85.2% did not have any documentation regarding exposure elsewhere. CONCLUSIONS:
      We found low concordance between the parent's report and the electronic medical
      record for smoke exposure and asthma education provided. Un- or under-documented
      smoke exposure and health education have the potential to affect continuity of
      care for pediatric patients with asthma.

PMID- 23883357
TI  - Specific in planta recognition of two GKLR proteins of the downy mildew Bremia
      lactucae revealed in a large effector screen in lettuce.
AB  - Breeding lettuce (Lactuca sativa) for resistance to the downy mildew pathogen
      Bremia lactucae is mainly achieved by introgression of dominant downy mildew
      resistance (Dm) genes. New Bremia races quickly render Dm genes ineffective,
      possibly by mutation of recognized host-translocated effectors or by suppression
      of effector-triggered immunity. We have previously identified 34 potential RXLR(
      like) effector proteins of B. lactucae that were here tested for specific
      recognition within a collection of 129 B. lactucae-resistant Lactuca lines. Two
      effectors triggered a hypersensitive response: BLG01 in 52 lines, predominantly
      L. saligna, and BLG03 in two L. sativa lines containing Dm2 resistance. The N
      terminal sequences of BLG01 and BLG03, containing the signal peptide and GKLR
      variant of the RXLR translocation motif, are not required for in planta
      recognition but function in effector delivery. The locus responsible for BLG01
      recognition maps to the bottom of lettuce chromosome 9, whereas recognition of
      BLG03 maps in the RGC2 cluster on chromosome 2. Lactuca lines that recognize the
      BLG effectors are not resistant to Bremia isolate Bl:24 that expresses both BLG
      genes, suggesting that Bl:24 can suppress the triggered immune responses. In
      contrast, lettuce segregants displaying Dm2-mediated resistance to Bremia isolate
      Bl:5 are responsive to BLG03, suggesting that BLG03 is a candidate Avr2 protein. 

PMID- 23883358
TI  - The Cpc1 regulator of the cross-pathway control of amino acid biosynthesis is
      required for pathogenicity of the vascular pathogen Verticillium longisporum.
AB  - The plant-pathogenic fungus Verticillium longisporum is a causal agent of early
      senescence and ripening in cruciferous crops like Brassica napus. Verticillium
      wilts have become serious agricultural threats in recent decades. Verticillium
      species infect host plants through the roots and colonize xylem vessels of the
      host plant. The xylem fluid provides an environment with limited carbon sources
      and unbalanced amino acid supply, which requires V. longisporum to induce the
      cross-pathway control of amino acid biosynthesis. RNA-mediated gene silencing
      reduced the expression of the two CPC1 isogenes (VlCPC1-1 and VlCPC1-2) of the
      allodiploid V. longisporum up to 85%. VlCPC1 encodes the conserved transcription
      factor of the cross-pathway control. The silenced mutants were highly sensitive
      to amino-acid starvation, and the infected plants showed significantly fewer
      symptoms such as stunting or early senescence in oilseed rape plant infection
      assays. Consistently, deletion of single CPC1 of the haploid V. dahliae resulted
      in strains that are sensitive to amino-acid starvation and cause strongly reduced
      symptoms in the plant-host tomato (Solanum lycopersicum). The allodiploid V.
      longisporum and the haploid V. dahliae are the first phytopathogenic fungi that
      were shown to require CPC1 for infection and colonization of their respective
      host plants, oilseed rape and tomato. 

PMID- 23883359
TI  - A nonribosomal peptide synthase containing a stand-alone condensation domain is
      essential for phytotoxin zeamine biosynthesis.
AB  - Dickeya zeae is the causal agent of rice foot rot and maize stalk rot diseases,
      which could cause severe economic losses. The pathogen is known to produce two
      phytotoxins known as zeamine and zeamine II which are also potent antibiotics
      against both gram-positive and gram-negative bacteria pathogens. Zeamine II is a
      long-chain aminated polyketide and zeamine shares the same polyketide structure
      as zeamine II, with an extra valine derivative moiety conjugated to the primary
      amino group of zeamine II. In this study, we have identified a gene designated as
      zmsK encoding a putative nonribosomal peptide synthase (NRPS) by screening of the
      transposon mutants defective in zeamine production. Different from most known
      NRPS enzymes, which are commonly multidomain proteins, ZmsK contains only a
      condensation domain. High-performance liquid chromatography and mass spectrometry
      analyses showed that the ZmsK deletion mutant produced only zeamine II but not
      zeamine, suggesting that ZmsK catalyzes the amide bond formation by using zeamine
      II as a substrate to generate zeamine. We also present evidence that a partially
      conserved catalytic motif within the condensation domain is critical for zeamine
      production. Furthermore, we show that deletion of zmsK substantially decreased
      the total antimicrobial activity and virulence of D. zeae. Our findings provide a
      new insight into the biosynthesis pathway of zeamines and the virulence
      mechanisms of the bacterial pathogen D. zeae. 

PMID- 23883360
TI  - Limiting prolonged inflammation during proliferation and remodeling phases of
      wound healing in streptozotocin-induced diabetic rats supplemented with camel
      undenatured whey protein.
AB  - BACKGROUND: Impaired diabetic wound healing occurs as a consequence of excessive
      reactive oxygen species (ROS) and inflammatory cytokine production. We previously
      found that whey protein (WP) was able to normally regulate the ROS and
      inflammatory cytokines during the inflammatory phase (first day) in
      streptozotocin (STZ)-diabetic wound healing. This study was designed to assess
      the effect of WP on metabolic status, the inflammation and anti-inflammation
      response, oxidative stress and the antioxidant defense system during different
      phases of the wound healing process in diabetic rats. WP at a dosage of 100 mg/kg
      of body weight, dissolved in 1% CMC, was orally administered daily to wounded
      normal (non-diabetic) and STZ-induced diabetic rats for 8 days starting from the
      1st day after wounding. RESULTS: The data revealed that WP enhanced wound closure
      and was associated with an increase in serum insulin levels in diabetic rats and
      an alleviation of hyperglycemic and hyperlipidemic states in diabetic animals.
      The increase in insulin levels as a result of WP administration is associated
      with a marked multiplication of beta-cells in the core of islets of Langerhans.
      WP induced a reduction in serum TNF-alpha, IL-1beta and IL-6 levels and an
      increase in IL-10 levels, especially on the 4th day after wounding and treatment.
      WP also suppressed hepatic lipid peroxidation and stimulated the antioxidant
      defense system by increasing the level of glutathione and the activity of
      glutathione-S-transferase, glutathione peroxidase and superoxide dismutase (SOD)
      in wounded diabetic rats. CONCLUSIONS: WP was observed to enhance wound closure
      by improving the diabetic condition, limiting prolonged inflammation, suppressing
      oxidative stress and elevating the antioxidant defense system in diabetic rats.

PMID- 23883361
TI  - Vaginal breech delivery: results of a prospective registration study.
AB  - BACKGROUND: Most countries recommend planned cesarean section in breech
      deliveries, which is considered safer than vaginal delivery. As one of few
      countries in the western world Norway has continued to practice planned vaginal
      delivery in selected women. The aim of this study is to evaluate prospectively
      registered neonatal and maternal outcomes in term singleton breech deliveries in
      a Norwegian hospital during a ten years period. We aim to compare maternal and
      neonatal outcomes in term breech pregnancies subjected either to planned vaginal
      or elective cesarean section. METHODS: A prospective registration study including
      568 women with term breech deliveries (>37 weeks) consecutively registered at
      Sorlandet Hospital Kristiansand between 2001 and 2011. Fetal and maternal
      outcomes were compared according to delivery method; planned vaginal delivery
      versus planned cesarean section. RESULTS: Of 568 women, elective cesarean section
      was planned in 279 (49%) cases and vaginal delivery was planned in 289 (51%)
      cases. Acute cesarean section was performed in 104 of the planned vaginal
      deliveries (36.3%). There were no neonatal deaths. Two cases of serious neonatal
      morbidity were reported in the planned vaginal group. One infant had seizures,
      brachial plexus injury, and cephalhematoma. The other infant had 5-minutes Apgar
      < 4. Twenty-nine in the planned vaginal group (10.0%) and eight in the planned
      cesarean section group (2.9%) (p < 0.001) were transferred to the neonatal
      intensive care unit. However, only one infant was admitted for >=4 days.
      According to follow-up data (median six years) none of these infants had long
      term sequelae. Regarding maternal morbidity, blood loss was the only variable
      that was significantly higher in the planned cesarean section group versus in the
      vaginal delivery group (p < 0.001). CONCLUSIONS: Strict guidelines were followed
      in all cases. There were no neonatal deaths. Two infants had serious neonatal
      morbidity in the planned vaginal group without long-term sequelae.

PMID- 23883362
TI  - A comparison of missing data procedures for addressing selection bias in HIV
      sentinel surveillance data.
AB  - BACKGROUND: Selection bias is common in clinic-based HIV surveillance. Clinics
      located in HIV hotspots are often the first to be chosen and monitored, while
      clinics in less prevalent areas are added to the surveillance system later on.
      Consequently, the estimated HIV prevalence based on clinic data is substantially
      distorted, with markedly higher HIV prevalence in the earlier periods and trends
      that reveal much more dramatic declines than actually occur. METHODS: Using
      simulations, we compare and contrast the performance of the various approaches
      and models for handling selection bias in clinic-based HIV surveillance. In
      particular, we compare the application of complete-case analysis and multiple
      imputation (MI). Several models are considered for each of the approaches. We
      demonstrate the application of the methods through sentinel surveillance data
      collected between 2002 and 2008 from India. RESULTS: Simulations suggested that
      selection bias, if not handled properly, can lead to biased estimates of HIV
      prevalence trends and inaccurate evaluation of program impact. Complete-case
      analysis and MI differed considerably in their ability to handle selection bias.
      In scenarios where HIV prevalence remained constant over time (i.e. beta = 0),
      the estimated beta^1 derived from MI tended to be biased downward. Depending on
      the imputation model used, the estimated bias ranged from -1.883 to -0.048 in
      logit prevalence. Furthermore, as the level of selection bias intensified, the
      extent of bias also increased. In contrast, the estimates yielded by complete
      case analysis were relatively unbiased and stable across the various scenarios.
      The estimated bias ranged from -0.002 to 0.002 in logit prevalence. CONCLUSIONS:
      Given that selection bias is common in clinic-based HIV surveillance, when
      analyzing data from such sources appropriate adjustment methods need to be
      applied. The results in this paper suggest that indiscriminant application of
      imputation models can lead to biased results.

PMID- 23883363
TI  - Theragnostic pH-sensitive gold nanoparticles for the selective surface enhanced
      Raman scattering and photothermal cancer therapy.
AB  - We report a nanoparticle-based probe that can be used for a "turn-on"
      theragnostic agent for simultaneous Raman imaging/diagnosis and photothermal
      therapy. The agent consists of a 10 nm spherical gold nanoparticle (NP) with pH
      responsive ligands and Raman probes on the surface. They are engineered to
      exhibit the surface with both positive and negative charges upon mildly acidic
      conditions, which subsequently results in rapid aggregations of the gold NPs.
      This aggregation simultaneously provides hot spots for the SERS probe with the
      enhancement factor reaching 1.3 * 10(4) and shifts the absorption to far-red and
      near-infrared (which is optimal for deep tissue penetration) by the coupled
      plasmon resonances; this shift was successfully exploited for low-threshold
      photothermal therapy. The theragnostic gold NPs are cancer-specific because they
      aggregate rapidly and accumulate selectively in cancerous cells. As the result,
      both Raman imaging and photothermal efficacy were turned on under a cancerous
      local environment. In addition, the relatively small hydrodynamic size can have
      the potential for better access to targeted delivery in vivo and facilitated
      excretion after therapy. 

PMID- 23883364
TI  - "Whole Chinese angelica" microemulsion: its preparation and in vivo and in vitro
      evaluations.
AB  - CONTEXT: The difference between the chemical polarities of the two categories of
      active chemical constituents in Chinese angelica volatile oil (CAVO) and Chinese
      angelica water extract (CAWE) greatly limit the development and clinical
      application of Chinese angelica preparation. OBJECT: The aim of this study is to
      design and prepare a "whole Chinese angelica" microemulsion (WCAM) that contains
      both CAVO and CAWE and at the same time to evaluate it in vivo and in vitro.
      MATERIALS AND METHODS: CAVO and CAWE extracted from Chinese angelica were used as
      the oil and aqueous phases, respectively, to prepare the WCAM; its
      physicochemical property was observed, and its drug potency and oral
      bioavailability were evaluated. RESULTS: The formula of the WCAM was optimized as
      Tween-80:ethanol:CAVO:CAWE = 3:3:1:40. The droplet size of the WCAM was 72.64 nm
      and the WCAM was proved to be physicochemically stable when it was kept at 0 
      degrees C, 4  degrees C, 25  degrees C and 40  degrees C for 3 months. The WCAM
      could markedly prolong blood clotting time, decrease whole blood viscosity and
      whole blood reduced viscosity at different shear rates, and improve
      hemorheological parameters. The results of the pharmacokinetic evaluation show
      that the AUC0-7 of the WCAM was 4510.66 and was about 4.41-fold compared to that
      of danggui concentrated pills (an existing Chinese angelica pharmaceutical
      preparation). CONCLUSION: It can be concluded, that the WCAM is a promising
      Chinese angelica preparation that has great prospects in the treatment of
      dysmenorrhea and irregular menstruation.

PMID- 23883365
TI  - Enhanced oral bioavailability of felodipine by naringenin in Wistar rats and
      inhibition of P-glycoprotein in everted rat gut sacs in vitro.
AB  - The aim of this study was to investigate the effect of naringenin on the
      pharmacokinetics (PK) of felodipine in rats and membrane permeability across rat
      everted gut sacs in vitro. Rats were simultaneously co-administered with
      felodipine 10 mg/kg, p.o. and naringenin (25, 50 and 100 mg/kg, p.o.) for 15
      consecutive days. Rats of the control groups received the corresponding volume of
      vehicle. Blood samples were withdrawn from retro-orbital plexus on first day in
      single dose PK study (SDS) and on 15th day in multiple dosing PK study (MDS). The
      PK parameters were calculated using Thermo kinetica. The co-administration of
      naringenin significantly elevated the Cmax and increased the AUCtotal of
      felodipine in dose-dependent manner. The Cmax of felodipine was increased from
      173.25 +/- 14.65 to 275.61 +/- 44.62 and 223.26 +/- 26.35 to 561.32 +/- 62.53
      ng/mL in SDS and MDS, respectively, at the dose of naringenin 100 mg/kg. The
      AUCtotal of felodipine was significantly (p < 0.001) increased from 2050.48 +/-
      60.57 to 3650.22 +/- 78.61 and 3276.51 +/- 325.61 to 7265.25 +/- 536.11 (ng/mL/h)
      in SDS and MDS, respectively. The permeability of felodipine was increased in
      presence of naringenin and ritonavir (standard P-glycoprotein (P-gp) and
      Cytochrome P450 (CYP)3A4 inhibitor). Felodipine is a substrate of CYP3A4, and
      naringenin was reported to be a modulator of P-gp and CYP3A4. These results
      suggest that naringenin significantly increased the Cmax and AUC of felodipine is
      due to P-gp and CYP3A4 inhibition.

PMID- 23883366
TI  - Dynamic length scales in glass-forming liquids: an inhomogeneous molecular
      dynamics simulation approach.
AB  - In this work, we numerically investigate a new method for the characterization of
      growing length scales associated with spatially heterogeneous dynamics of glass
      forming liquids. This approach, motivated by the formulation of the inhomogeneous
      mode-coupling theory (IMCT) [Biroli, G.; et al. Phys. Rev. Lett. 2006 97,
      195701], utilizes inhomogeneous molecular dynamics simulations in which the
      system is perturbed by a spatially modulated external potential. We show that the
      response of the two-point correlation function to the external field allows one
      to probe dynamic correlations. We examine the critical properties shown by this
      function, in particular, the associated dynamic correlation length, that is found
      to be comparable to the one extracted from standardly employed four-point
      correlation functions. Our numerical results are in qualitative agreement with
      IMCT predictions but suggest that one has to take into account fluctuations not
      included in this mean-field approach to reach quantitative agreement. Advantages
      of our approach over the more conventional one based on four-point correlation
      functions are discussed. 

PMID- 23883367
TI  - The characteristics of a good clinical teacher as perceived by resident
      physicians in Japan: a qualitative study.
AB  - BACKGROUND: It is not known whether the characteristics of a good clinical
      teacher as perceived by resident physicians are the same in Western countries as
      in non-Western countries including Japan. The objective of this study was to
      identify the characteristics of a good clinical teacher as perceived by resident
      physicians in Japan, a non-Western country, and to compare the results with those
      obtained in Western countries. METHODS: Data for this qualitative research were
      collected using semi-structured focus group interviews. Focus group transcripts
      were independently analyzed and coded by three authors. Residents were recruited
      by maximum variation sampling until thematic saturation was achieved. RESULTS:
      Twenty-three residents participated in five focus group interviews regarding the
      perceived characteristics of a good clinical teacher in Japan. The 197
      descriptions of characteristics that were identified were grouped into 30 themes.
      The most commonly identified theme was "provided sufficient support", followed by
      "presented residents with chances to think", "provided feedback", and "provided
      specific indications of areas needing improvement". Using Sutkin's main
      categories (teacher, physician, and human characteristics), 24 of the 30 themes
      were categorized as teacher characteristics, 6 as physician characteristics, and
      none as human characteristics. CONCLUSIONS: "Medical knowledge" of teachers was
      not identified as a concern of residents, and "clinical competence of teachers"
      was not emphasized, whereas these were the two most commonly recorded themes in
      Sutkin's study. Our results suggest that Japanese and Western resident physicians
      place emphasis on different characteristics of their teachers. We speculate that
      such perceptions are influenced by educational systems, educational settings, and
      culture. Globalization of medical education is important, but it is also
      important to consider differences in educational systems, local settings, and
      culture when evaluating clinical teachers.

PMID- 23883368
TI  - Neural stem cell sparing by linac based intensity modulated stereotactic
      radiotherapy in intracranial tumors.
AB  - BACKGROUND: Neurocognitive decline observed after radiotherapy (RT) for brain
      tumors in long time survivors is attributed to radiation exposure of the
      hippocampus and the subventricular zone (SVZ). The potential of sparing
      capabilities for both structures by optimized intensity modulated stereotactic
      radiotherapy (IMSRT) is investigated. METHODS: Brain tumors were irradiated by
      stereotactic 3D conformal RT or IMSRT using m3 collimator optimized for PTV and
      for sparing of the conventional OARs (lens, retina, optic nerve, chiasm, cochlea,
      brain stem and the medulla oblongata). Retrospectively both hippocampi and SVZ
      were added to the list of OAR and their dose volume histograms were compared to
      those from two newly generated IMSRT plans using 7 or 14 beamlets (IMSRT-7, IMSRT
      14) dedicated for optimized additional sparing of these structures. Conventional
      OAR constraints were kept constant. Impact of plan complexity and planning target
      volume (PTV) topography on sparing of both hippocampi and SVZ, conformity index
      (CI), the homogeneity index (HI) and quality of coverage (QoC) were analyzed.
      Limits of agreement were used to compare sparing of stem cell niches with either
      IMSRT-7 or IMSRT-14. The influence of treatment technique related to the
      topography ratio between PTV and OARs, realized in group A-D, was assessed by a
      mixed model. RESULTS: In 47 patients CI (p <=  0.003) and HI (p  <  0.001)
      improved by IMSRT-7, IMSRT-14, QoC remained stable (p  >=  0.50) indicating no
      compromise in radiotherapy. 90% of normal brain was exposed to a significantly
      higher dose using IMSRT. IMSRT-7 plans resulted in significantly lower
      biologically effective doses at all four neural stem cell structures, while
      contralateral neural stem cells are better spared compared to ipsilateral. A
      further increase of the number of beamlets (IMSRT-14) did not improve sparing
      significantly, so IMSRT-7 and IMSRT-14 can be used interchangeable. Patients with
      tumors contacting neither the subventricular zone nor the cortex benefit most
      from IMSRT (p  <  0.001). CONCLUSION: The feasibility of neural stem cell niches
      sparing with sophisticated linac based inverse IMSRT with 7 beamlets in an
      unselected cohort of intracranial tumors in relation to topographic situation has
      been demonstrated. Clinical relevance testing neurotoxicity remains to be
      demonstrated.

PMID- 23883369
TI  - Effect of Trichinella spiralis infection on the immune response to HBV vaccine in
      a mouse model.
AB  - Vaccination is the most effective and cost-effective way to treat hepatitis B
      virus (HBV) infection. Collective data suggest that helminth infections affect
      immune responses to some vaccines. Therefore, it is important to reveal the
      effects of helminth infections on the efficacy of protective vaccines in
      countries with highly prevalent helminth infections. In the present work, effects
      of Trichinella spiralis infection on the protective efficacy of HBV vaccine in a
      mouse model were investigated. This study demonstrated that the enteric stage of
      T. spiralis infection could inhibit the proliferative response of spleen
      lymphocytes to hepatitis B surface antigen (HBsAg) and lead to lower levels of
      anti-HBsAg antibodies, interferon-gamma, and interleukin (IL)-2, along with
      higher levels of IL-4 and IL-5. However, these immunological differences are
      absent in the muscle stage of T. spiralis infection. The results suggest that the
      muscle stage of T. spiralis infection does not affect the immune response to HBV
      vaccination, while the enteric-stage infection results in a reduced immune
      response to HBsAg.

PMID- 23883370
TI  - The impact of cranioplasty on neurological function.
AB  - OBJECTIVES: To assess changes in neurological function after cranioplasty.
      METHODS: Functional and neurocognitive assessments including activities of daily
      living assessment, functional independence measure (FIM) and the Cognitive
      assessment report (COGNISTAT) were conducted on all patients within 72 h before
      and 7 days after cranioplasty. A change in the total FIM score of 2 points was
      taken to be clinically significant. RESULTS: Assessments were performed on 25
      patients. The functional status was unchanged in eighteen patients (72%), four
      patients (16%) demonstrated a significant improvement and three patients (12%)
      deteriorated significantly. Those with deterioration after cranioplasty had some
      forms of complications including pneumocephalus or seizure. After excluding the
      three patients who had immediate medical or surgical complications after surgery,
      there was a mild overall improvement in the mean FIM score (2.1, 95% confidence
      interval 0.1-4.3, p = 0.049), mainly due to an improvement in their motor
      function. CONCLUSIONS: A small but significant number of patients appear to
      improve clinically following cranioplasty. The so-called syndrome of the
      trephined may be more common than had been previously appreciated.

PMID- 23883371
TI  - 'Goose bumps' as presenting feature of intraventricular glioblastoma multiforme.
AB  - 'Goose-bumps' seizures are rare manifestations of epilepsy. They are rarely
      reported by patients and can be easily dismissed by clinicians. Clinically, it
      carries some diagnostic localising value especially with unilateral onset. In
      this report, we present a case of intraventricular glioblastoma multiforme with
      ipsilateral goose bumps and review the literature.

PMID- 23883372
TI  - Long-term follow-up of patients with tumours of the renal pelvis and ureter: how
      often is a bladder tumour diagnosed after five tumour-free years?
AB  - OBJECTIVE: It is not known when cystoscopy follow-up should be terminated after
      surgery for tumours of the renal pelvis and ureter [upper urinary tract tumours
      (UUTTs)]. The aim of this study was to investigate the length of the interval
      from surgery to diagnosis of the first bladder tumour. MATERIAL AND METHODS: A
      review was performed of all 930 patients who were diagnosed with a UUTT from 1971
      to 1998 in western Sweden. The time to the first bladder tumour was estimated
      using Kaplan--Meier analyses. Univariate and multivariate analyses of potential
      risk factors for bladder recurrence were performed. RESULTS: In total, 614
      patients were treated surgically for a renal pelvic or ureteral tumour and
      underwent cystoscopy at least 3 months afterwards. Of these 614 patients,192
      (31.3%) patients developed a bladder tumour after the upper tract surgery. The
      majority, 157 out of 192 patients (81.8%), were diagnosed during the first 2
      years, an additional 24 patients (12.5%) during years 3--5 and 11 patients (5.7%)
      between years 5 and 20. A history of bladder tumours, large tumour diameter,
      carcinoma in situ and UUTT diagnosed during the last part of the study period
      were significant risk factors for bladder recurrence after upper tract surgery.
      CONCLUSION: Cystoscopy should be performed at short intervals during the first 2
      years after surgery for a UUTT, in particular among patients with a history of
      bladder tumours. Late bladder recurrences are unusual; therefore, as a rule,
      follow-up cystoscopy should be terminated after 5 tumour-free years.

PMID- 23883373
TI  - Ruthenium-catalyzed ortho-alkenylation of phenylphosphine oxides through regio-
      and stereoselective alkyne insertion into C-H bonds.
AB  - Direct ortho-substitution took place efficiently upon treatment of tri-, di-, and
      monoarylphosphine oxides with internal alkynes in the presence of a ruthenium
      catalyst to produce (o-alkenylphenyl)phosphine oxides regio- and
      stereoselectively. Chemoselective reduction of a product gave the corresponding
      (o-alkenylphenyl)phosphine, which may be useful as a ligand for transition
      metals. 

PMID- 23883374
TI  - Rifampicin-associated acute renal failure and hemolysis: a rather uncommon but
      severe complication.
AB  - Rifampicin is a widely used anti-tuberculosis agent. Apart from hepatotoxicity,
      rifampicin can rarely lead to adverse reactions of immunologic nature such as
      acute renal failure (ARF). We report the case of 57-year-old previously healthy
      man under treatment for pulmonary tuberculosis who presented with hemolysis and
      severe ARF. Rifampicin was discontinued and the patient was treated with fluid
      repletion, iv furosemide and dialysis therapy. Kidney biopsy revealed acute
      tubulointerstitial nephritis with no evidence of granulomas. The patient
      significantly improved and was discharged after 51 days of hospitalization.
      Clinicians using rifampicin should be aware of this rather uncommon but severe
      complication.

PMID- 23883375
TI  - Accountable prescribing.

PMID- 23883376
TI  - Observation care--high-value care or a cost-shifting loophole?

PMID- 23883377
TI  - Riociguat for the treatment of chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Riociguat, a member of a new class of compounds (soluble guanylate
      cyclase stimulators), has been shown in previous clinical studies to be
      beneficial in the treatment of chronic thromboembolic pulmonary hypertension.
      METHODS: In this phase 3, multicenter, randomized, double-blind, placebo
      controlled study, we randomly assigned 261 patients with inoperable chronic
      thromboembolic pulmonary hypertension or persistent or recurrent pulmonary
      hypertension after pulmonary endarterectomy to receive placebo or riociguat. The
      primary end point was the change from baseline to the end of week 16 in the
      distance walked in 6 minutes. Secondary end points included changes from baseline
      in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT
      proBNP) level, World Health Organization (WHO) functional class, time to clinical
      worsening, Borg dyspnea score, quality-of-life variables, and safety. RESULTS: By
      week 16, the 6-minute walk distance had increased by a mean of 39 m in the
      riociguat group, as compared with a mean decrease of 6 m in the placebo group
      (least-squares mean difference, 46 m; 95% confidence interval [CI], 25 to 67;
      P<0.001). Pulmonary vascular resistance decreased by 226 dyn.sec.cm(-5) in the
      riociguat group and increased by 23 dyn.sec.cm(-5) in the placebo group (least
      squares mean difference, -246 dyn.sec.cm(-5); 95% CI, -303 to -190; P<0.001).
      Riociguat was also associated with significant improvements in the NT-proBNP
      level (P<0.001) and WHO functional class (P=0.003). The most common serious
      adverse events were right ventricular failure (in 3% of patients in each group)
      and syncope (in 2% of the riociguat group and in 3% of the placebo group).
      CONCLUSIONS: Riociguat significantly improved exercise capacity and pulmonary
      vascular resistance in patients with chronic thromboembolic pulmonary
      hypertension. (Funded by Bayer HealthCare; CHEST-1 and CHEST-2 ClinicalTrials.gov
      numbers, NCT00855465 and NCT00910429, respectively.)

PMID- 23883379
TI  - A phase 3 trial of semagacestat for treatment of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease is characterized by the presence of cortical
      amyloid-beta (Abeta) protein plaques, which result from the sequential action of
      beta-secretase and gamma-secretase on amyloid precursor protein. Semagacestat is
      a small-molecule gamma-secretase inhibitor that was developed as a potential
      treatment for Alzheimer's disease. METHODS: We conducted a double-blind, placebo
      controlled trial in which 1537 patients with probable Alzheimer's disease
      underwent randomization to receive 100 mg of semagacestat, 140 mg of
      semagacestat, or placebo daily. Changes in cognition from baseline to week 76
      were assessed with the use of the cognitive subscale of the Alzheimer's Disease
      Assessment Scale for cognition (ADAS-cog), on which scores range from 0 to 70 and
      higher scores indicate greater cognitive impairment, and changes in functioning
      were assessed with the Alzheimer's Disease Cooperative Study-Activities of Daily
      Living (ADCS-ADL) scale, on which scores range from 0 to 78 and higher scores
      indicate better functioning. A mixed-model repeated-measures analysis was used.
      RESULTS: The trial was terminated before completion on the basis of a
      recommendation by the data and safety monitoring board. At termination, there
      were 189 patients in the group receiving placebo, 153 patients in the group
      receiving 100 mg of semagacestat, and 121 patients in the group receiving 140 mg
      of semagacestat. The ADAS-cog scores worsened in all three groups (mean change,
      6.4 points in the placebo group, 7.5 points in the group receiving 100 mg of the
      study drug, and 7.8 points in the group receiving 140 mg; P=0.15 and P=0.07,
      respectively, for the comparison with placebo). The ADCS-ADL scores also worsened
      in all groups (mean change at week 76, -9.0 points in the placebo group, -10.5
      points in the 100-mg group, and -12.6 points in the 140-mg group; P=0.14 and
      P<0.001, respectively, for the comparison with placebo). Patients treated with
      semagacestat lost more weight and had more skin cancers and infections, treatment
      discontinuations due to adverse events, and serious adverse events (P<0.001 for
      all comparisons with placebo). Laboratory abnormalities included reduced levels
      of lymphocytes, T cells, immunoglobulins, albumin, total protein, and uric acid
      and elevated levels of eosinophils, monocytes, and cholesterol; the urine pH was
      also elevated. CONCLUSIONS: As compared with placebo, semagacestat did not
      improve cognitive status, and patients receiving the higher dose had significant
      worsening of functional ability. Semagacestat was associated with more adverse
      events, including skin cancers and infections. (Funded by Eli Lilly;
      ClinicalTrials.gov number, NCT00594568.)

PMID- 23883378
TI  - Riociguat for the treatment of pulmonary arterial hypertension.
AB  - BACKGROUND: Riociguat, a soluble guanylate cyclase stimulator, has been shown in
      a phase 2 trial to be beneficial in the treatment of pulmonary arterial
      hypertension. METHODS: In this phase 3, double-blind study, we randomly assigned
      443 patients with symptomatic pulmonary arterial hypertension to receive placebo,
      riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5
      mg-maximum group), or riociguat in individually adjusted doses that were capped
      at 1.5 mg three times daily (1.5 mg-maximum group). The 1.5 mg-maximum group was
      included for exploratory purposes, and the data from that group were analyzed
      descriptively. Patients who were receiving no other treatment for pulmonary
      arterial hypertension and patients who were receiving endothelin-receptor
      antagonists or (nonintravenous) prostanoids were eligible. The primary end point
      was the change from baseline to the end of week 12 in the distance walked in 6
      minutes. Secondary end points included the change in pulmonary vascular
      resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World
      Health Organization (WHO) functional class, time to clinical worsening, score on
      the Borg dyspnea scale, quality-of-life variables, and safety. RESULTS: By week
      12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg
      maximum group and had decreased by a mean of 6 m in the placebo group (least
      squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001).
      Prespecified subgroup analyses showed that riociguat improved the 6-minute walk
      distance both in patients who were receiving no other treatment for the disease
      and in those who were receiving endothelin-receptor antagonists or prostanoids.
      There were significant improvements in pulmonary vascular resistance (P<0.001),
      NT-proBNP levels (P<0.001), WHO functional class (P=0.003), time to clinical
      worsening (P=0.005), and Borg dyspnea score (P=0.002). The most common serious
      adverse event in the placebo group and the 2.5 mg-maximum group was syncope (4%
      and 1%, respectively). CONCLUSIONS: Riociguat significantly improved exercise
      capacity and secondary efficacy end points in patients with pulmonary arterial
      hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2
      ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.).

PMID- 23883381
TI  - Mechanisms of hypoglycemia-associated autonomic failure in diabetes.

PMID- 23883380
TI  - A novel channelopathy in pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension is a devastating disease with high
      mortality. Familial cases of pulmonary arterial hypertension are usually
      characterized by autosomal dominant transmission with reduced penetrance, and
      some familial cases have unknown genetic causes. METHODS: We studied a family in
      which multiple members had pulmonary arterial hypertension without identifiable
      mutations in any of the genes known to be associated with the disease, including
      BMPR2, ALK1, ENG, SMAD9, and CAV1. Three family members were studied with whole
      exome sequencing. Additional patients with familial or idiopathic pulmonary
      arterial hypertension were screened for the mutations in the gene that was
      identified on whole-exome sequencing. All variants were expressed in COS-7 cells,
      and channel function was studied by means of patch-clamp analysis. RESULTS: We
      identified a novel heterozygous missense variant c.608 G->A (G203D) in KCNK3 (the
      gene encoding potassium channel subfamily K, member 3) as a disease-causing
      candidate gene in the family. Five additional heterozygous missense variants in
      KCNK3 were independently identified in 92 unrelated patients with familial
      pulmonary arterial hypertension and 230 patients with idiopathic pulmonary
      arterial hypertension. We used in silico bioinformatic tools to predict that all
      six novel variants would be damaging. Electrophysiological studies of the channel
      indicated that all these missense mutations resulted in loss of function, and the
      reduction in the potassium-channel current was remedied by the application of the
      phospholipase inhibitor ONO-RS-082. CONCLUSIONS: Our study identified the
      association of a novel gene, KCNK3, with familial and idiopathic pulmonary
      arterial hypertension. Mutations in this gene produced reduced potassium-channel
      current, which was successfully remedied by pharmacologic manipulation. (Funded
      by the National Institutes of Health.)

PMID- 23883382
TI  - Images in clinical medicine. A half-red baby.

PMID- 23883383
TI  - Riociguat for pulmonary hypertension--a glass half full.

PMID- 23883384
TI  - Mapping the journey to an HIV vaccine.

PMID- 23883385
TI  - PCI at hospitals with or without on-site cardiac surgery.

PMID- 23883386
TI  - PCI at hospitals with or without on-site cardiac surgery.

PMID- 23883387
TI  - Platelet inhibition with cangrelor during PCI.

PMID- 23883388
TI  - Platelet inhibition with cangrelor during PCI.

PMID- 23883389
TI  - Images in clinical medicine. Symmetric lipomatosis of the tongue.

PMID- 23883390
TI  - Boron-doped peroxo-zirconium oxide dielectric for high-performance, low
      temperature, solution-processed indium oxide thin-film transistor.
AB  - We developed a solution-processed indium oxide (In2O3) thin-film transistor (TFT)
      with a boron-doped peroxo-zirconium (ZrO2:B) dielectric on silicon as well as
      polyimide substrate at 200  degrees C, using water as the solvent for the In2O3
      precursor. The formation of In2O3 and ZrO2:B films were intensively studied by
      thermogravimetric differential thermal analysis (TG-DTA), attenuated total
      reflectance Fourier transform infrared spectroscopy (ATR-FT IR), high-resolution
      X-ray diffraction (HR-XRD), and X-ray photoelectron spectroscopy (XPS). Boron was
      selected as a dopant to make a denser ZrO2 film. The ZrO2:B film effectively
      blocked the leakage current at 200  degrees C with high breakdown strength. To
      evaluate the ZrO2:B film as a gate dielectric, we fabricated In2O3 TFTs on the
      ZrO2:B dielectrics with silicon substrates and annealed the resulting samples at
      200 and 250  degrees C. The resulting mobilities were 1.25 and 39.3 cm(2)/(V s),
      respectively. Finally, we realized a flexible In2O3 TFT with the ZrO2:B
      dielectric on a polyimide substrate at 200  degrees C, and it successfully
      operated a switching device with a mobility of 4.01 cm(2)/(V s). Our results
      suggest that aqueous solution-processed In2O3 TFTs on ZrO2:B dielectrics could
      potentially be used for low-cost, low-temperature, and high-performance flexible
      devices. 

PMID- 23883391
TI  - The social context of career choice among millennial nurses: implications for
      interprofessional practice.
AB  - Health human resource and workforce planning is a global priority. Given the
      critical nursing shortage, and the fact that nurses are the largest group of
      healthcare providers, health workforce planning must focus on strategies to
      enhance both recruitment and retention of nurses. Understanding early
      socialization to career choice can provide insight into professional perceptions
      and expectations that have implications for recruitment, retention and
      interprofessional collaboration. This interpretive narrative inquiry utilized
      Polkinghorne's theory of narrative emplotment to understand the career choice
      experiences of 12 millennial nurses (born between 1980 and 2000) in Eastern
      Canada. Participants were interviewed twice, face-to-face, 4 to 6 weeks apart
      prior to commencing their nursing program. The narratives present career choice
      as a complex consideration of social positioning. The findings provide insight
      into how nursing is perceived to be positioned in relation to medicine and how
      the participants struggled to locate themselves within this social hierarchy.
      Implications of this research highlight the need to ensure that recruitment
      messaging and organizational policies promote interprofessional collaboration
      from the onset of choosing a career in the health professions. Early professional
      socialization strategies during recruitment and education can enhance future
      collaboration between the health professions.

PMID- 23883392
TI  - Medical students' interprofessional experiences in a rehabilitation and
      palliative care placement.
AB  - The majority of interprofessional learning literature focuses on initiatives
      within pre-clinical or simulated learning environments, with a paucity of
      research exploring the variation in impact of exposure to nurses and other health
      professionals in different health care settings. This study aimed to explore the
      experiences and attitudes of medical students following scheduled placements in
      palliative and rehabilitative care units. Three focus groups were conducted by
      researchers independent of the clinical school, to explore the attitudes of first
      clinical year medical students towards, and experiences of, a clinical placement
      that provided the opportunity to develop interprofessional skills. Students
      responded differently to the expectation put upon them to initiate their own
      learning experiences. A number of students felt that being asked to focus on
      clinical skill development conflicted with the assessment demands of the medical
      curriculum. This, in turn, contributed to a missed opportunity for them to learn
      with, from and about nurses and other health professionals. The driver of
      assessment was seen to be more important to their training. This emphasises the
      importance of including an assessment of interprofessional skills if we want to
      ensure students achieve these skills. If medical students are not going to be
      assessed on interprofessional knowledge, skills and attitudes then a curriculum
      orientation to the value of interprofessional practice is required.

PMID- 23883393
TI  - Mild and general palladium-catalyzed synthesis of methyl aryl ethers enabled by
      the use of a palladacycle precatalyst.
AB  - A general method for the Pd-catalyzed coupling of methanol with (hetero)aryl
      halides is described. The reactions proceed under mild conditions with a wide
      range of aryl and heteroaryl halides to give methyl aryl ethers in high yield. 

PMID- 23883394
TI  - The (*)OH radical yield in the H2O2 + O3 (peroxone) reaction.
AB  - The peroxone process is one of the AOPs that lead to (*)OH. Hitherto, it has been
      generally assumed that the (*)OH yield is unity with respect to O3 consumption.
      Here, experimental data are presented that suggest that it must be near 0.5. The
      first evidence is derived from competition experiments. The consumption of 4
      chlorobenzoic acid (4-CBA), 4-nitrobenzoic acid (4-NBA) and atrazine present in
      trace amounts (1 MUM) has been followed as a function of the O3 concentration in
      a solution containing H2O2 (1 mM) and tertiary butanol (tBuOH, 0.5 mM) in excess
      over the trace compounds. With authentic (*)OH generated by gamma-radiolysis such
      a competition can be adequately fitted by known (*)OH rate constants. Fitting the
      peroxone data, however, the consumption of the trace indicators can only be
      rationalized if the (*)OH yield is near 0.5 (4-CBA: 0.56, 4-NBA: 0.49, atrazine:
      0.6). Additional information for an (*)OH yield much below unity has been
      obtained by a product analysis of the reactions of tBuOH with (*)OH and dimethyl
      sulfoxide with (*)OH. The mechanistic interpretation for the low (*)OH yield is
      as follows (Merenyi et al. Environ. Sci. Technol. 2010, 44, 3505-3507). In the
      reaction of O3 with HO2(-) an adduct (HO5(-)) is formed that decomposes into O3(*
      ) and HO2(*) in competition with 2 O2 + OH(-). The latter process reduces the
      free-radical yield. 

PMID- 23883395
TI  - Increased river alkalinization in the Eastern U.S.
AB  - The interaction between human activities and watershed geology is accelerating
      long-term changes in the carbon cycle of rivers. We evaluated changes in
      bicarbonate alkalinity, a product of chemical weathering, and tested for long
      term trends at 97 sites in the eastern United States draining over 260,000 km(2).
      We observed statistically significant increasing trends in alkalinity at 62 of
      the 97 sites, while remaining sites exhibited no significant decreasing trends.
      Over 50% of study sites also had statistically significant increasing trends in
      concentrations of calcium (another product of chemical weathering) where data
      were available. River alkalinization rates were significantly related to
      watershed carbonate lithology, acid deposition, and topography. These three
      variables explained ~40% of variation in river alkalinization rates. The
      strongest predictor of river alkalinization rates was carbonate lithology. The
      most rapid rates of river alkalinization occurred at sites with highest inputs of
      acid deposition and highest elevation. The rise of alkalinity in many rivers
      throughout the Eastern U.S. suggests human-accelerated chemical weathering, in
      addition to previously documented impacts of mining and land use. Increased river
      alkalinization has major environmental implications including impacts on water
      hardness and salinization of drinking water, alterations of air-water exchange of
      CO2, coastal ocean acidification, and the influence of bicarbonate availability
      on primary production.

PMID- 23883396
TI  - Twelve tips for designing and running longitudinal integrated clerkships.
AB  - Longitudinal integrated clerkships (LICs) involve learners spending an extended
      time in a clinical setting (or a variety of interlinked clinical settings) where
      their clinical learning opportunities are interwoven through continuities of
      patient contact and care, continuities of assessment and supervision, and
      continuities of clinical and cultural learning. Our twelve tips are grounded in
      the lived experiences of designing, implementing, maintaining, and evaluating
      LICs, and in the extant literature on LICs. We consider: general issues
      (anticipated benefits and challenges associated with starting and running an
      LIC); logistical issues (how long each longitudinal experience should last, where
      it will take place, the number of learners who can be accommodated); and
      integration issues (how the LIC interfaces with the rest of the program, and the
      need for evaluation that aligns with the dynamics of the LIC model). Although
      this paper is primarily aimed at those who are considering setting up an LIC in
      their own institutions or who are already running an LIC we also offer our
      recommendations as a reflection on the broader dynamics of medical education and
      on the priorities and issues we all face in designing and running educational
      programs. 

PMID- 23883397
TI  - Single-electrode-based sliding triboelectric nanogenerator for self-powered
      displacement vector sensor system.
AB  - We report a single-electrode-based sliding-mode triboelectric nanogenerator
      (TENG) that not only can harvest mechanical energy but also is a self-powered
      displacement vector sensor system for touching pad technology. By utilizing the
      relative sliding between an electrodeless polytetrafluoroethylene (PTFE) patch
      with surface-etched nanoparticles and an Al electrode that is grounded, the
      fabricated TENG can produce an open-circuit voltage up to 1100 V, a short-circuit
      current density of 6 mA/m(2), and a maximum power density of 350 mW/m(2) on a
      load of 100 MOmega, which can be used to instantaneously drive 100 green-light
      emitting diodes (LEDs). The working mechanism of the TENG is based on the charge
      transfer between the Al electrode and the ground by modulating the relative
      sliding distance between the tribo-charged PTFE patch and the Al plate. Grating
      of linear rows on the Al electrode enables the detection of the sliding speed of
      the PTFE patch along one direction. Moreover, we demonstrated that 16 Al
      electrode channels arranged along four directions were used to monitor the
      displacement (the direction and the location) of the PTFE patch at the center,
      where the output voltage signals in the 16 channels were recorded in real-time to
      form a mapping figure. The advantage of this design is that it only requires the
      bottom Al electrode to be grounded and the top PTFE patch needs no electrical
      contact, which is beneficial for energy harvesting in automobile rotation mode
      and touch pad applications. 

PMID- 23883398
TI  - Autonomous replication of nucleic acids by polymerization/nicking enzyme/DNAzyme
      cascades for the amplified detection of DNA and the aptamer-cocaine complex.
AB  - The progressive development of amplified DNA sensors and aptasensors using
      replication/nicking enzymes/DNAzyme machineries is described. The sensing
      platforms are based on the tailoring of a DNA template on which the recognition
      of the target DNA or the formation of the aptamer-substrate complex trigger on
      the autonomous isothermal replication/nicking processes and the displacement of a
      Mg(2+)-dependent DNAzyme that catalyzes the generation of a fluorophore-labeled
      nucleic acid acting as readout signal for the analyses. Three different DNA
      sensing configurations are described, where in the ultimate configuration the
      target sequence is incorporated into a nucleic acid blocker structure associated
      with the sensing template. The target-triggered isothermal autonomous
      replication/nicking process on the modified template results in the formation of
      the Mg(2+)-dependent DNAzyme tethered to a free strand consisting of the target
      sequence. This activates additional template units for the nucleic acid self
      replication process, resulting in the ultrasensitive detection of the target DNA
      (detection limit 1 aM). Similarly, amplified aptamer-based sensing platforms for
      cocaine are developed along these concepts. The modification of the cocaine
      detection template by the addition of a nucleic acid sequence that enables the
      autonomous secondary coupled activation of a polymerization/nicking machinery and
      DNAzyme generation path leads to an improved analysis of cocaine (detection limit
      10 nM). 

PMID- 23883399
TI  - Iridium(I) complexes with anionic N-heterocyclic carbene ligands as catalysts for
      the hydrogenation of alkenes in nonpolar media.
AB  - A series of lithium complexes of anionic N-heterocyclic carbenes that contain a
      weakly coordinating borate moiety (WCA-NHC) was prepared in one step from free N
      heterocyclic carbenes by deprotonation with n-butyl lithium followed by borane
      addition. The reaction of the resulting lithium-carbene adducts with [M(COD)Cl]2
      (M = Rh, Ir; COD = 1,5-cyclooctadiene) afforded zwitterionic rhodium(I) and
      iridium(I) complexes of the type [(WCA-NHC)M(COD)], in which the metal atoms
      exhibit an intramolecular interaction with the N-aryl groups of the carbene
      ligands. For M = Rh, the neutral complex [(WCA-NHC)Rh(CO)2] and the ate complex
      (NEt4)[(WCA-NHC)Rh(CO)2Cl] were prepared, with the latter allowing an assessment
      of the donor ability of the ligand by IR spectroscopy. The zwitterionic iridium
      COD complexes were tested as catalysts for the homogeneous hydrogenation of
      alkenes, which can be performed in the presence of nonpolar solvents or in the
      neat alkene substrate. Thereby, the most active complex showed excellent
      stability and activity in hydrogenation of alkenes at low catalyst loadings (down
      to 10 ppm). 

PMID- 23883401
TI  - Unexpected catalytic performance in silent tantalum oxide through nitridation and
      defect chemistry.
AB  - This work reports on the preparation of a noble-metal-free and highly active
      catalyst that proved to be an efficient and green reductant with renewable
      capacity. Nitridation of a silent Ta1.1O1.05 substrate led to the formation of a
      series of TaOxNy hollow nanocrystals that exhibited outstanding activity toward
      catalytic reduction of nitrobenzenes under ambient conditions. ESR and XPS
      results indicated that defective nitrogen species and oxygen vacancies at the
      surfaces of the TaOxNy nanocrystals may play synergetic roles in the reduction of
      nitrobenzenes. The underlying mechanism is completely different from those
      previously reported for metallic nanoparticles. This work may provide new
      possibilities for the development of novel defect-meditated catalytic systems and
      offer a strategy for tuning any catalysts from silent to highly reactive by
      carefully tailoring the chemical composition and surface defect chemistry. 

PMID- 23883403
TI  - InAs-mediated growth of vertical InSb nanowires on Si substrates.
AB  - In this work, InSb nanowires are grown vertically on Si (111) with metal organic
      chemical vapor deposition using InAs as seed layer, instead of external metal
      catalyst. Two groups of InSb nanowires are fabricated and characterized: one
      group presents Indium droplets at the nanowire's free end, while the other, in
      contrast, ends without Indium droplet but with pyramid-shaped InSb. The indium
      droplet-ended nanowires are longer than the other group of nanowires. For both
      groups of InSb nanowires, InAs layers play an important role in their formation
      by serving as a template for growing InSb nanowires. The results presented in
      this work suggest a useful approach to grow catalyst-free InSb nanowires on Si
      substrates, which is significant for their device applications. 

PMID- 23883402
TI  - Functional promoter -31G/C variant of Survivin gene predict prostate cancer
      susceptibility among Chinese: a case control study.
AB  - BACKGROUND: Abnormal expression of Baculoviral inhibitor of apoptosis repeat
      containing 5 (BIRC5, also called as survivin), a novel member of the inhibitor of
      apoptosis protein (IAP) family, has implications in many types of cancer and is
      considered as a new therapeutic target. We suppose that genetic variant rs9904341
      in the 5' UTR region of survivin gene may be associated with the development and
      progression of prostate cancer (PCa) in Chinese population. METHODS: TaqMan assay
      method was used to genotype the polymorphism in the hospital-based case-control
      analysis of 665 patients with PCa and 710 age-matched cancer-free controls. The
      genetic associations with the occurrence and progression of PCa were calculated
      by logistic regression. RESULTS: Our results indicated that compared with GG
      genotypes, there was a statistically significant increased risk of PCa associated
      with those with CC genotypes [odds ratios (ORs) = 1.57, 95%confidence intervals
      (CIs) = 1.17-2.13, P = 0.004]. Moreover, stratification analysis revealed that
      the association was more pronounced in subgroups of nondrinkers, nonsmokers and
      those without a family history of cancer (all P < 0.05). In addition, we observed
      that PSA >= 20 was more frequent in patients carrying GC/CC genotypes than in
      those with a wild type genotype. CONCLUSION: The functional survivin rs9904341
      genetic variant may have a substantial influence on the PCa susceptibility and
      evolution.

PMID- 23883404
TI  - Characterization of the PAS domain in the sensor-kinase BvgS: mechanical role in
      signal transmission.
AB  - BACKGROUND: In bacteria, signal-transduction two-component systems are major
      players for adaptation to environmental stimuli. The perception of a chemical or
      physical signal by a sensor-kinase triggers its autophosphorylation. The
      phosphoryl group is then transferred to the cognate response regulator, which
      mediates the appropriate adaptive response. Virulence of the whooping cough agent
      Bordetella pertussis is controlled by the two-component system BvgAS. Atypically,
      the sensor-kinase BvgS is active without specific stimuli at 37 degrees C in
      laboratory conditions and is inactivated by the addition of negative chemical
      modulators. The structure of BvgS is complex, with two tandem periplasmic Venus
      flytrap domains and a cytoplasmic PAS domain that precedes the kinase domain,
      which is followed by additional phosphotransfer domains. PAS domains are small,
      ubiquitous sensing or regulatory domains. The function of the PAS domain in BvgS
      remains unknown. RESULTS: We showed that recombinant BvgS PAS proteins form
      dimers that are stabilized by alpha helical regions flanking the PAS core. A
      structural model of the PAS domain dimer was built and probed by site-directed
      mutagenesis and by biochemical and functional analyses. Although we found no
      ligands for the PAS domain cavity, its integrity is required for signaling. We
      also showed that the structural stability of the PAS core and its proper coupling
      to its flanking N- and C-terminal alpha helices are crucial for BvgS activity.
      CONCLUSIONS: We propose that a major function of the BvgS PAS domain is to
      maintain conformational signals arising from mechanical strain generated by the
      periplasmic domain. The tight structure of the PAS core and its connections with
      the upstream and downstream helices ensure signaling to the kinase domain, which
      determines BvgS activity. Many mild substitutions that map to the PAS domain keep
      BvgS active but make it unresponsive to negative modulators, supporting that
      modulation increases conformational strain in the protein.

PMID- 23883405
TI  - The effect of adjusting for baseline hypoglycemia when analyzing hypoglycemia
      data: a systematic analysis of 15 diabetes clinical trials.
AB  - BACKGROUND: Baseline hypoglycemia rates are generally not collected or included
      as a covariate in statistical models used for analyzing hypoglycemia data. The
      objective of the present study was to examine the effect of adjusting for
      baseline hypoglycemia on estimation efficiency and statistical power. SUBJECTS
      AND METHODS: A post hoc analysis of data from 15 insulin trials, including
      patients with type 1 diabetes mellitus (T1DM) (n=210), previously insulin-treated
      type 2 diabetes mellitus (T2DM) (n=1,511), or T2DM and previously insulin-naive
      (n=1,075). Hypoglycemic episodes were analyzed with a negative binomial
      regression model. RESULTS: Baseline nocturnal hypoglycemia rate was significantly
      correlated with post-baseline nocturnal hypoglycemia rate in previously insulin
      treated patients with T1DM and T2DM (correlation range, 0.37-0.63; P<0.001).
      Adjusting for baseline hypoglycemia resulted in a reduction in the SE for
      negative binomial regression for previously insulin-treated patients with T1DM
      and T2DM (range, 2.2-11.8%) and increased statistical power. Modeling of
      lengthening the lead-in period increases the correlation between baseline and
      post-baseline hypoglycemia event rate and statistical power. CONCLUSIONS:
      Baseline hypoglycemia rate is significantly correlated with post-baseline
      hypoglycemia rate for patients with diabetes treated with insulin prior to
      randomization. The length of the lead-in period can impact correlations between
      baseline and post-baseline data, and adjustment for baseline hypoglycemia may
      improve the estimation efficiency for hypoglycemia data analyses in clinical
      trials.

PMID- 23883406
TI  - A novel adaptive-weighted-average framework for blood glucose prediction.
AB  - BACKGROUND: Blood glucose (BG) prediction plays a very important role in daily BG
      management of patients with diabetes mellitus. Several algorithms, such as
      autoregressive (AR) models and artificial neural networks, have been proposed for
      BG prediction. However, every algorithm has its own subject range (i.e., one
      algorithm might work well for one diabetes patient but poorly for another
      patient). Even for one individual patient, this algorithm might perform well
      during the preprandial period but poorly during the postprandial period.
      MATERIALS AND METHODS: A novel framework was proposed to combine several BG
      prediction algorithms. The main idea of the novel framework is that an adaptive
      weight is given to each algorithm where one algorithm's weight is inversely
      proportional to the sum of the squared prediction errors. In general, this
      framework can be applied to combine any BG prediction algorithms. RESULTS: As an
      example, the proposed framework was used to combine an AR model, extreme learning
      machine, and support vector regression. The new algorithm was compared with these
      three prediction algorithms on the continuous glucose monitoring system (CGMS)
      readings of 10 type 1 diabetes mellitus patients; the CGMS readings of each
      patient included 860 CGMS data points. For each patient, the algorithms were
      evaluated in terms of root-mean-square error, relative error, Clarke error-grid
      analysis, and J index. Of the 40 evaluations, the new adaptive-weighted algorithm
      achieved the best prediction performance in 37 (92.5%). CONCLUSIONS: Thus, we
      conclude that the adaptive-weighted-average framework proposed in this study can
      give satisfactory predictions and should be used in BG prediction. The new
      algorithm has great robustness with respect to variations in data
      characteristics, patients, and prediction horizons. At the same time, it is
      universal.

PMID- 23883407
TI  - System accuracy of blood glucose monitoring systems: impact of use by patients
      and ambient conditions.
AB  - For self-monitoring of blood glucose by people with diabetes, the reliability of
      the measured blood glucose values is a prerequisite in order to ensure correct
      therapeutic decisions. Requirements for system accuracy are defined by the
      International Organization for Standardization (ISO) in the standard EN ISO
      15197:2003. However, even a system with high analytical quality is not a
      guarantee for accurate and reliable measurement results. Under routine life
      conditions, blood glucose measurement results are affected by several factors.
      First, the act of performing measurements as well as the handling of the system
      may entail numerous possible error sources, such as traces of glucose-containing
      products on the fingertips, the use of deteriorated test strips, or the incorrect
      storage of test strips. Second, ambient and sampling conditions such as high
      altitude, partial pressure of oxygen, ambient temperature, and the use of
      alternate test sites can have an influence on measurement results. Therefore, the
      user-friendliness of a system and the quality of the manufacturer's labeling to
      reduce the risk of handling errors are also important aspects in ensuring
      reliable and accurate measurement results. In addition, the analytical
      performance of systems should be less prone to user errors and ambient
      conditions. Finally, people with diabetes must be aware of the information and
      instructions in the manufacturer's labeling and must be able to measure and
      interpret blood glucose results correctly.

PMID- 23883408
TI  - Outpatient safety assessment of an in-home predictive low-glucose suspend system
      with type 1 diabetes subjects at elevated risk of nocturnal hypoglycemia.
AB  - OBJECTIVE: Nocturnal hypoglycemia is a common problem with type 1 diabetes. In
      the home setting, we conducted a pilot study to evaluate the safety of a system
      consisting of an insulin pump and continuous glucose monitor communicating
      wirelessly with a bedside computer running an algorithm that temporarily suspends
      insulin delivery when hypoglycemia is predicted. RESEARCH DESIGN AND METHODS:
      After the run-in phase, a 21-night randomized trial was conducted in which each
      night was randomly assigned 2:1 to have either the predictive low-glucose suspend
      (PLGS) system active (intervention night) or inactive (control night). Three
      predictive algorithm versions were studied sequentially during the study for a
      total of 252 intervention and 123 control nights. The trial included 19
      participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0
      7.7%) who were current users of the MiniMed Paradigm(r) REAL-Time RevelTM System
      and Sof-sensor(r) glucose sensor (Medtronic Diabetes, Northridge, CA). RESULTS:
      With the final algorithm, pump suspension occurred on 53% of 77 intervention
      nights. Mean morning glucose level was 144+/-48 mg/dL on the 77 intervention
      nights versus 133+/-57 mg/dL on the 37 control nights, with morning blood ketones
      >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on
      intervention than control nights, with at least one value <=70 mg/dL occurring on
      16% versus 30% of nights, respectively, with the final algorithm. CONCLUSIONS:
      This study demonstrated that the PLGS system in the home setting is safe and
      feasible. The preliminary efficacy data appear promising with the final algorithm
      reducing nocturnal hypoglycemia by almost 50%.

PMID- 23883409
TI  - Pseudonymization of patient identifiers for translational research.
AB  - BACKGROUND: The usage of patient data for research poses risks concerning the
      patients' privacy and informational self-determination. Next-generation
      sequencing technologies and various other methods gain data from biospecimen,
      both for translational research and personalized medicine. If these biospecimen
      are anonymized, individual research results from genomic research, which should
      be offered to patients in a clinically relevant timeframe, cannot be associated
      back to the individual. This raises an ethical concern and challenges the
      legitimacy of anonymized patient samples. In this paper we present a new approach
      which supports both data privacy and the possibility to give feedback to patients
      about their individual research results. METHODS: We examined previously
      published privacy concepts regarding a streamlined de-pseudonymization process
      and a patient-based pseudonym as applicable to research with genomic data and
      warehousing approaches. All concepts identified in the literature review were
      compared to each other and analyzed for their applicability to translational
      research projects. We evaluated how these concepts cope with challenges
      implicated by personalized medicine. Therefore, both person-centricity issues and
      a separation of pseudonymization and de-pseudonymization stood out as a central
      theme in our examination. This motivated us to enhance an existing
      pseudonymization method regarding a separation of duties. RESULTS: The existing
      concepts rely on external trusted third parties, making de-pseudonymization a
      multistage process involving additional interpersonal communication, which might
      cause critical delays in patient care. Therefore we propose an enhanced method
      with an asymmetric encryption scheme separating the duties of pseudonymization
      and de-pseudonymization. The pseudonymization service provider is unable to
      conclude the patient identifier from the pseudonym, but assigns this ability to
      an authorized third party (ombudsman) instead. To solve person-centricity issues,
      a collision-resistant function is incorporated into the method. These two facts
      combined enable us to address essential challenges in translational research. A
      productive software prototype was implemented to prove the functionality of the
      suggested translational, data privacy-preserving method. Eventually, we performed
      a threat analysis to evaluate potential hazards connected with this
      pseudonymization method. CONCLUSIONS: The proposed method offers sustainable
      organizational simplification regarding an ethically indicated, but secure and
      controlled process of de-pseudonymizing patients. A pseudonym is patient-centered
      to allow correlating separate datasets from one patient. Therefore, this method
      bridges the gap between bench and bedside in translational research while
      preserving patient privacy. Assigned ombudsmen are able to de-pseudonymize a
      patient, if an individual research result is clinically relevant.

PMID- 23883410
TI  - Long-term impact of positive surgical margins on biochemical recurrence after
      radical prostatectomy: ten years of follow-up.
AB  - OBJECTIVE: Positive surgical margins (PSMs) in men undergoing radical
      prostatectomy (RP) for prostate cancer are associated with an increased risk of
      biochemical recurrence. This study evaluated the long-term (>10 year) impact of
      PSMs on biochemical recurrence after RP in adjuvant treatment-naive pT2-pT4 N0
      men and determined predictors of prostate-specific antigen (PSA) failure.
      MATERIAL AND METHODS: The institutional registry of 1276 patients who underwent
      RP at Henri Mondor Hospital from 1988 to 2001 was reviewed, identifying 403
      patients with regular follow-up at the time of analysis. The study included 108
      patients with PSMs who did not receive neoadjuvant or adjuvant therapy before PSA
      relapse. Median follow-up was 12.2 years. PSA failure was defined by a PSA rising
      by more than 0.2 ng/ml and biochemical recurrence-free survival (RFS) was
      estimated using the Kaplan-Meier method. Cox proportional hazard regression
      models were used to analyse clinicopathological variables associated with
      biochemical recurrence. RESULTS: Biochemical recurrence 10 years after RP was
      33.5% for patients regardless of the margin status. The 10-year biochemical RFS
      was 73% in men with negative margins compared to 49% in the case of PSM (p <
      0.001). In multivariate analysis, margin status was a significantly predictive
      for PSA failure (hazard ratio 1.46, p = 0.04). After stratification by
      pathological stage, margin status was significantly predictive for biochemical
      RFS in pT2 (p < 0.001) and pT3a (p < 0.001), whereas the impact of PSM did not
      reach significance in pT3b (p = 0.16). CONCLUSIONS: After 10-year follow-up, PSMs
      remain an independent risk factor of biochemical RFS after RP with less relevant
      impact in pT3b disease. Randomized prospective trials are needed to determine the
      place of adjuvant versus delayed radiotherapy.

PMID- 23883411
TI  - Sequencing of the grxB gene of Cronobacter spp. and the development of a PCR
      assay for its identification.
AB  - Cronobacter spp. (formerly Enterobacter sakazakii), a foodborne pathogen linked
      to powdered infant formula, is a rare cause of invasive infection with a high
      mortality rate in neonates. In this study, the Cronobacter sakazakii ATCC 29544
      and C. muytjensii ATCC 51329 glutaredoxin 2 (grxB) genes were cloned and
      sequenced. Based on the unique regions of the Cronobacter grxB genes, two primers
      were synthesized to develop and optimize a Cronobacter-specific polymerase chain
      reaction (PCR) method. The PCR assay amplified a 378-bp DNA product from all
      positive controls, which are composed of 45 strains of Cronobacter spp., but not
      from any of 45 non-Cronobacter bacterial strains. The detection limits of this
      method are 10(4) colony-forming units (CFU)/mL of Cronobacter spp. in infant
      formula directly and 10(0) CFU/mL after an 8-h enrichment step. In summary, we
      have developed a PCR assay based on the grxB sequence. Combined with enrichment
      culturing, this technique offers a rapid and sensitive method for the detection
      of Cronobacter spp.

PMID- 23883412
TI  - Serum omentin-1, inflammation and carotid atherosclerosis in patients with non
      diabetic chronic kidney disease.
AB  - BACKGROUND AND AIM: Omentin-1 is suggested to affect inversely atherosclerosis
      (AS). Data about omentin-1 is limited to chronic kidney disease (CKD). Our aim
      was to examine omentin-1 in non-diabetic CKD patients who are not dialyzed and
      investigate its relationships with inflammation and carotid AS. MATERIALS AND
      METHODS: We performed a cross-sectional study in 55 non-diabetic CKD patients and
      30 healthy controls. Baseline clinical and laboratory data were obtained for all
      participants. Serum omentin-1 and interleukin-6 (IL-6) levels were measured
      according to the manufacturer's instructions. Carotic plaque and intima-media
      thickness (IMT) were assessed by carotid ultrasonography. The homeostasis model
      assessment of insulin resistance index (HOMA-IR) was used to assess IR. RESULTS:
      Omentin-1 and IL-6 levels in the patient group were found to be higher than the
      control group; the differences were statistically significant (p = 0.01 and p =
      0.04, respectively). Carotid IMT(mean) was significantly higher in the patient
      group (p = 0.01). Omentin-1 did not correlate with IL-6 and IMT in the patient
      group (p = 0.51 and p = 0.76, respectively). In subgroup analysis, omentin-1
      levels in patients with carotid plaque were lower than those without carotid
      plaque (179.5 +/- 88.1 ng/ml and 185.9 +/- 67.8 ng/ml, respectively). However,
      the difference was not statistically significant (p = 0.47). CONCLUSION: We
      conclude that omentin-1 is higher in not dialyzed non-diabetic CKD and there is
      no correlation between omentin-1 and IL-6 or carotid IMT(mean).

PMID- 23883413
TI  - Reoperation for failed shoulder reconstruction following brachial plexus birth
      injury.
AB  - BACKGROUND: Various approaches have been developed to treat the progressive
      shoulder deformity in patients with brachial plexus birth palsy. Reconstructive
      surgery for this condition consists of complex procedures with a risk for
      failure. CASE PRESENTATIONS: This is a retrospective case review of the outcome
      in eight cases referred to us for reoperation for failed shoulder
      reconstructions. In each case, we describe the initial attempt(s) at surgical
      correction, the underlying causes of failure, and the procedures performed to
      rectify the problem. Results were assessed using pre- and post-operative Mallet
      shoulder scores. All eight patients realized improvement in shoulder function
      from reoperation. CONCLUSIONS: This case review identifies several aspects of
      reconstructive shoulder surgery for brachial plexus birth injury that may cause
      failure of the index procedure(s) and outlines critical steps in the evaluation
      and execution of shoulder reconstruction.

PMID- 23883414
TI  - New ionization processes and applications for use in mass spectrometry.
AB  - Mass spectrometry (MS) continues to improve at a rapid pace as most prominently
      witnessed for mass analyzers and fragmentation technology. Ionization methods
      have also seen resurgence with ambient ionization approaches gaining a foothold
      because they often provide a convenient and direct means of sample analysis.
      Nevertheless, a vast majority of biological analyses using MS apply electrospray
      ionization or matrix-assisted laser desorption/ionization, methods introduced in
      the 1980s, or variants thereof. To further advance applications by MS such as
      protein characterization, and, for example, addressing their location within
      specific cell types, the progress in mass analyzer and fragmentation technology
      needs to be matched with similar advances in ionization technology. It is
      imperative to seek ionization methods that more efficiently convert molecules, to
      gas-phase ions in a way that allows high transfer efficiency to the mass analyzer
      and subsequently the detector to achieve a more complete picture of sample
      composition. This review provides a snapshot of fundamental aspects of new
      ionization methods and potential biological and medical applications.

PMID- 23883415
TI  - Palladium(II)-catalyzed enantioselective synthesis of alpha
      (trifluoromethyl)arylmethylamines.
AB  - Trifluoromethylacetaldimines, generated in situ from the corresponding N,O
      acetals, undergo 1,2-addition of arylboroxines under palladium(II) catalysis to
      generate a variety of alpha-(trifluoromethyl)arylmethylamines with good to high
      enantioselectivity (up to 97% ee). The pyridine-oxazolidine (PyOX) class of
      ligands was found to be particularly suitable for this transformation, which
      proceeds without exclusion of ambient air and moisture. 

PMID- 23883416
TI  - Estimated medical cost reductions associated with apixaban in real-world patients
      with non-valvular atrial fibrillation.
AB  - OBJECTIVE: The Apixaban for Reduction in Stroke and Other Thromboembolic Events
      in Atrial Fibrillation (ARISTOTLE) trial demonstrated that apixaban was effective
      in reducing the risk of stroke and major bleeding in non-valvular atrial
      fibrillation (NVAF) patients. Medical cost avoidance studies for oral
      anticoagulants have used warfarin event rates from clinical trials, which may not
      reflect the real-world (RW) setting. This study aimed to estimate the difference
      in medical costs associated with apixaban instead of warfarin in RW NVAF
      patients. METHODS: This study selected patients with NVAF diagnosis during 2007
      2010 from a Medco population of US commercial and Medicare health plans. Stroke
      and major bleeding excluding intracranial hemorrhage (MBEIH) were identified
      using diagnosis codes. Pharmacy claims were used to define warfarin exposure
      periods. Rates of stroke and MBEIH were calculated during warfarin exposure. To
      estimate the absolute risk reduction (ARR) between warfarin and apixaban in RW,
      the relative risk reductions (RRR) from ARISTOTLE were multiplied by the event
      rates observed in RW during warfarin exposure. Medical cost reductions associated
      with apixaban were calculated by applying the ARR to the 1-year incremental cost
      for each event. Stroke and MBEIH costs were obtained from the literature and
      adjusted to 2011 levels. RESULTS: During a patient year, the use of apixaban
      instead of warfarin resulted in medical cost reductions of $493 for stroke and
      $752 for MBEIH and $1245 for the combined outcome of both events. The medical
      costs avoided were greater as baseline stroke risk increased. CONCLUSION: If RRRs
      demonstrated in ARISTOTLE persist in RW, the use of apixaban will be associated
      with lower medical costs vs warfarin. Main limitations of this study were:
      identification of clinical events using administrative codes rather than
      confirmatory clinical data, inability to evaluate the level of international
      normalized ratio (INR) control, and not including INR monitoring and drug costs.

PMID- 23883417
TI  - Occurrence of brominated persistent organic pollutants (PBDD/DFs, PXDD/DFs, and
      PBDEs) in Baltic wild salmon ( Salmo salar ) and correlation with PCDD/DFs and
      PCBs.
AB  - The contamination profiles of polybrominated dibenzo-p-dioxins (PBDDs),
      dibenzofurans (PBDFs), diphenyl ethers (PBDEs), and mixed monobromo/chloro
      dibenzo-p-dioxins (PXDDs) and dibenzofurans (PXDFs) were determined in the tissue
      of Baltic wild salmon and compared with those of polychlorinated dibenzo-p
      dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs). Out of the analyzed
      PXDD/DFs, only the 3-B-2,7,8-triCDF was detected (in the concentration range of
      0.039-0.075 pg g(-1) fresh weight (f.w.)). The toxic equivalents (TEQs) for
      analyzed PBDD/DFs (0.074-0.142 pg TEQ g(-1) f.w.) were found to contribute on
      average 2.1% to the total PCDD/DF-PBDD/DF-TEQ. The total concentrations of 27
      PBDE congeners were in the range of 1.3-5.6 ng g(-1) f.w., with an average of 3.3
      ng g(-1) f.w. The levels of PCDD/DFs and PCBs were found to be in the range of
      4.53-14.6 pg WHO(2005)-PCDD/DF-PCB-TEQ g(-1) f.w., and concentrations of these
      compounds in most of the analyzed samples were above the maximum levels specified
      in Commission Regulation (EU) No. 1259/2011. Good correlation was observed
      between WHO(2005)-PCDD/DF-TEQ and WHO(2005)-PCB-TEQ (r(2) = 0.98), and these
      parameters were well correlated with the total sum of PBDE concentrations (r(2) =
      0.91 and r(2) = 0.94, respectively). The results suggest that the consumption of
      Baltic wild salmon has no crucial impact on the average POP intake for typical
      Latvians. 

PMID- 23883418
TI  - Chemical unzipping of WS2 nanotubes.
AB  - WS2 nanoribbons have been synthesized by chemical unzipping of WS2 nanotubes.
      Lithium atoms are intercalated in WS2 nanotubes by a solvothermal reaction with n
      butyllithium in hexane. The lithiated WS2 nanotubes are then reacted with various
      solvents--water, ethanol, and long chain thiols. While the tubes break into
      pieces when treated with water and ethanol, they unzip through longitudinal
      cutting along the axes to yield nanoribbons when treated with long chain thiols,
      1-octanethiol and 1-dodecanethiol. The slow diffusion of the long chain thiols
      reduces the aggression of the reaction, leading to controlled opening of the
      tubes.

PMID- 23883419
TI  - Design and synthesis of heterobimetallic Ru(II)-Ln(III) complexes as
      chemodosimetric ensembles for the detection of biogenic amine odorants.
AB  - The detection of neutral biogenic amines plays a crucial role in food safety.
      Three new heterobimetallic Ru(II)-Ln(III) donor-acceptor complexes, KPrRu, KNdRu,
      and KSmRu, K{[Ru((II))((t)Bubpy)(CN)4]2-Ln((III))(H2O)4} (where (t)Bubpy = 4,4'
      di-tert-butyl-2,2'-bipyridine), have been synthesized and characterized. Their
      photophysical and X-ray crystallographic data were reported in this study. These
      complexes were found to be selective for biogenic amine vapors, such as
      histamine, putrescine, and spermidine, with a detection limit down to the ppb
      level. The sensitivities of these complexes to the amines were recorded as ~log K
      = 3.6-5.0. Submicron rods of the complexes, with a nanoscale diameter and
      microscale length, were obtained through a simple precipitation process. Free
      standing polymeric films with different degrees of porosity were fabricated by
      blending the submicron rods with polystyrene polymer. The polymer with the
      highest level of porosity exhibited the strongest luminescence enhancement after
      amine exposure. Real time monitoring of gaseous biogenic amines was applied to
      real fish samples (Atlantic mackerel) by studying the spectrofluorimetric
      responses of the Ru(II)-Ln(III) blended polymer film.

PMID- 23883420
TI  - A systematic review of qualitative studies on adjusting after stroke: lessons for
      the study of resilience.
AB  - PURPOSE: To synthesize qualitative studies on adjusting after stroke, from stroke
      survivors' and carers' perspectives, and to outline their potential contribution
      to an understanding of resilience. METHODS: A systematic review of qualitative
      studies in peer reviewed journals from 1990 to 2011 was undertaken. Findings from
      selected studies were summarized and synthesized and then considered alongside
      studies of resilience. RESULTS: Forty studies were identified as suitable. These
      suggested that the impact of stroke was felt on many dimensions of experience,
      and that the boundaries between these were permeable. Nor was stroke as an
      adverse "event" temporally bounded. Adjustment was often marked by setbacks and
      new challenges over time. Participants identified personal characteristics as
      key, but also employed practical and mental strategies in their efforts to
      adjust. Relationships and structural factors also influenced adjustment after
      stroke. CONCLUSIONS: The impacts of stroke and the processes of adjusting to it
      unfold over time. This presents a new challenge for resilience research.
      Processes of adjustment, like resilience, draw on personal, inter-personal and
      structural resources. But the reviewed studies point to the importance of an emic
      perspective on adversity, social support, and what constitutes a "good" outcome
      when researching resilience, and to a greater focus on embodiment. Implications
      for Rehabilitation Stroke is a sudden onset condition which for around a third of
      people has long-term consequences. Stroke can cause a variety of physical and
      cognitive impairments, some of which may not be obvious to an outsider. As well
      as physical functioning, stroke can have a profound effect on survivors' sense of
      self and on their relationships. Stroke survivors' accounts suggest that
      relationships (including relationships with health care professionals) and
      structural factors (such as access to health services, employment possibilities
      and welfare systems) mediate efforts to adjust after stroke. While there is
      considerable overlap between notions of adjustment and resilience, the
      experiences of stroke survivors suggest further issues that need to be addressed
      in order to gain a more comprehensive understanding of resilience.

PMID- 23883421
TI  - Community participation for girls and women living with Rett syndrome.
AB  - OBJECTIVE: To describe the relationships between impairment and contextual
      factors and community participation for girls and women with Rett syndrome.
      METHODS: Data was collected from a questionnaire completed in 2009 by families
      participating in the Australian Rett Syndrome Database (n = 214). Univariate and
      multivariate logistic regression were used to analyse relationships between
      impairment, personal and environmental factors and community participation.
      RESULTS: The mean age of the girls and women was 17.6 years (SD = 7.95, range 3
      to 34 years) with 114 (53.3%) girls still at school and 100 (46.7%) women post
      school. Frequency of activities was influenced by level of walking, community
      support and maternal education. For girls living at home, participation in
      activities was associated with greater functional independence and higher levels
      of maternal education. Participation in recreational (90.1%), physical/skill
      based (67.6%) and/or social (70.3%) activities was commonly reported by families,
      while self-improvement (17.6%) activities were less reported. Younger girls
      participated in activities mainly with family members and older girls more
      frequently participated with carers. CONCLUSION: Participation for girls and
      women with Rett syndrome could be enhanced by stronger local community supports.
      There are also needs for the implementation of policies that ensure resources are
      available and accessible by those communities most in need.

PMID- 23883422
TI  - Analytic solutions for some reaction-diffusion scenarios.
AB  - Motivated currently by the problem of coalescence of receptor clusters in mast
      cells in the general subject of immune reactions, and formerly by the
      investigation of exciton trapping and sensitized luminescence in molecular
      systems and aggregates, we present analytic expressions for survival
      probabilities of moving entities undergoing diffusion and reaction on encounter.
      Results we provide cover several novel situations in simple 1-d systems as well
      as higher-dimensional counterparts along with a useful compendium of such
      expressions in chemical physics and allied fields. We also emphasize the
      importance of the relationship of discrete sink term analysis to continuum
      boundary condition studies. 

PMID- 23883423
TI  - Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases
      from Brazil.
AB  - BACKGROUND: Invasive cervical cancer is the second most common malignant tumor
      affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in
      invasive cervical cancer cases is crucial to guide the introduction and further
      evaluate the impact of new preventive strategies based on HPV. We aimed to
      provide updated comprehensive data about the HPV types' distribution in patients
      with invasive cervical cancer. METHODS: Fresh tumor tissue samples of
      histologically confirmed invasive cervical cancer were collected from 175 women
      attending two cancer reference hospitals from Sao Paulo State: ICESP and Hospital
      de Cancer de Barretos. HPV detection and genotyping were performed by the Linear
      Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). RESULTS:
      170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types
      were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%).
      Most infections (75%) were caused by individual HPV types. Women with
      adenocarcinoma were not younger than those with squamous cell carcinoma, as well,
      as women infected with HPV33 were older than those infected by other HPV types.
      Some differences between results obtained in the two hospitals were observed:
      higher overall prevalence of HPV16, absence of single infection by HPV31 and
      HPV45 was verified in HC-Barretos in comparison to ICESP patients. CONCLUSIONS:
      To our knowledge, this is one of the largest studies made with fresh tumor
      tissues of invasive cervical cancer cases in Brazil. This study depicted a
      distinct HPV genotype distribution between two centers that may reflect the local
      epidemiology of HPV transmission among these populations. Due to the impact of
      these findings on cervical cancer preventive strategies, extension of this
      investigation to routine screening populations is warranted.

PMID- 23883424
TI  - Factors affecting pediatric isotonic fluid resuscitation efficiency: a randomized
      controlled trial evaluating the impact of syringe size.
AB  - BACKGROUND: Goal-directed therapy guidelines for pediatric septic shock
      resuscitation recommend fluid delivery at speeds in excess of that possible
      through use of regular fluid infusion pumps. In our experience, syringes are
      commonly used by health care providers (HCPs) to achieve rapid fluid
      resuscitation in a pediatric fluid resuscitation scenario. At present, it is
      unclear which syringe size health care providers should use when performing fluid
      resuscitation to achieve maximal fluid resuscitation efficiency. The objective of
      this study was therefore to determine if an optimal syringe size exists for
      conducting manual pediatric fluid resuscitation. METHODS: This 48-participant
      parallel group randomized controlled trial included 4 study arms (10, 20, 30, 60
      mL syringe size groups). Eligible participants were HCPs from McMaster Children's
      Hospital, Hamilton, Canada blinded to the purpose of the trial. Consenting
      participants were randomized using a third party technique. Following a
      standardization procedure, participants administered 900 mL (60 mL/kg) of
      isotonic saline to a simulated 15 kg child using prefilled provided syringes of
      the allocated size in rapid sequence. Primary outcome was total time to
      administer the 900 mL and this data was collected through video review by two
      blinded outcome assessors. Sample size was predetermined based upon a primary
      outcome analysis using one-way ANOVA. RESULTS: 12 participants were randomized to
      each group (n=48) and all completed trial protocol to analysis. Analysis was
      conducted according to intention to treat principles. A significant difference in
      fluid resuscitation time (in seconds) was found between syringe size group means:
      10 mL, 563s [95% CI 521; 606]; 20 mL, 506s [95% CI 64; 548]; 30 mL, 454s [95% CI
      412; 596]; 60 mL, 455s [95% CI 413; 497] (p<0.001). CONCLUSIONS: The syringe size
      used when performing manual pediatric fluid resuscitation has a significant
      impact on fluid resuscitation speed, in a setting where fluid filled syringes are
      continuously available. Greatest efficiency was achieved with 30 or 60 mL
      syringes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01494116.

PMID- 23883426
TI  - Structural variability in multifunctional metal xylenediaminetetraphosphonate
      hybrids.
AB  - Two new families of divalent metal hybrid derivatives from the aromatic
      tetraphosphonic acids 1,4- and 1,3-bis(aminomethyl)benzene-N,N'
      bis(methylenephosphonic acid), (H2O3PCH2)2-N-CH2C6H4CH2-N(CH2PO3H2)2 (designated
      herein as p-H8L and m-H8L) have been synthesized by crystallization at room
      temperature and hydrothermal conditions. The crystal structures of
      M[(HO3PCH2)2N(H)CH2C6H4CH2N(H)(CH2PO3H)2(H2O)2].2H2O (M = Mg, Co, and Zn), M-(p
      H6L), and M[(HO3PCH2)2N(H)CH2C6H4CH2N(H)(CH2PO3H)2].nH2O (M = Ca, Mg, Co, and Zn
      and n = 1-1.5), M-(m-H6L), were solved ab initio by synchrotron powder
      diffraction data using the direct methods and subsequently refined using the
      Rietveld method. The crystal structure of the isostructural M-(p-H6L) is
      constituted by organic-inorganic monodimensional chains where the phosphonate
      moiety acts as a bidentate chelating ligand bridging two metal octahedra. M-(m
      H6L) compounds exhibit a 3D pillared open-framework with small 1D channels filled
      with water molecules. These channels are formed by the pillaring action of the
      organic ligand connecting adjacent layers through the phosphonate oxygens.
      Thermogravimetric and X-ray thermodiffraction analyses of M-(p-H6L) showed that
      the integrity of their crystalline structures is maintained up to 470 K, without
      significant reduction of water content, while thermal decomposition takes place
      above 580 K. The utility of M-(p-H6L) (M = Mg and Zn) hybrid materials in
      corrosion protection was investigated in acidic aqueous solutions. In addition,
      the impedance data indicate both families of compounds display similar proton
      conductivities (sigma ~ 9.4 * 10(-5) S.cm(-1), at 98% RH and 297 K), although
      different proton transfer mechanisms are involved. 

PMID- 23883427
TI  - The Study of Active Monitoring in Sweden (SAMS): a randomized study comparing two
      different follow-up schedules for active surveillance of low-risk prostate
      cancer.
AB  - OBJECTIVE: Only a minority of patients with low-risk prostate cancer needs
      treatment, but the methods for optimal selection of patients for treatment are
      not established. This article describes the Study of Active Monitoring in Sweden
      (SAMS), which aims to improve those methods. MATERIAL AND METHODS: SAMS is a
      prospective, multicentre study of active surveillance for low-risk prostate
      cancer. It consists of a randomized part comparing standard rebiopsy and follow
      up with an extensive initial rebiopsy coupled with less intensive follow-up and
      no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS
      ObsQoL). Quality of life is assessed with questionnaires and compared with
      patients receiving primary curative treatment. SAMS-FU is planned to randomize
      500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The
      primary endpoint is conversion to active treatment. The secondary endpoints
      include symptoms, distant metastases and mortality. All patients will be followed
      for 10-15 years. RESULTS: Inclusion started in October 2011. In March 2013, 148
      patients were included at 13 Swedish urological centres. CONCLUSIONS: It is hoped
      that the results of SAMS will contribute to fewer patients with indolent, low
      risk prostate cancer receiving unnecessary treatment and more patients on active
      surveillance who need treatment receiving it when the disease is still curable.
      The less intensive investigational follow-up in the SAMS-FU trial would reduce
      the healthcare resources allocated to this large group of patients if it replaced
      the present standard schedule.

PMID- 23883428
TI  - Prediction of fraction metabolized via CYP3A in humans utilizing cryopreserved
      human hepatocytes from a set of 12 single donors.
AB  - 1.  It has previously been demonstrated that metabolism of drugs via a single
      enzymatic pathway, particularly CYP3A4, is associated with increased risk for
      drug-drug interactions (DDI). Quantitative experimental systems as well as
      integrated prediction models to assess such risk during the preclinical phase are
      highly warranted. 2.  The present study was designed to systematically
      investigate the performance of human cryopreserved hepatocytes in suspension to
      predict fraction metabolized via CYP3A (fmCYP3A) by assessing the ketoconazole
      sensitive intrinsic clearance (CLint) for five prototypical CYP3A substrates with
      varying degree of CYP3A dependent CLint in twelve individual hepatocyte batches.
      3.  We demonstrate that in contrast to well predicted mean hepatic metabolic
      clearance (CLH) and mean fmCYP3A data, the variability in CYP3A contribution for
      compounds having multiple metabolic pathways cannot be predicted from inhibition
      experiments using ketoconazole as inhibitor. Instead, data in the present paper
      indicate that the variability is larger after inhibition of CYP3A for compounds
      having multiple metabolic pathways. 4.  It is therefore recommended to estimate
      the average CLint and fmCYP3A for a given test compound in a series (n = 10) of
      individual human hepatocyte batches.

PMID- 23883429
TI  - One-step synthesis of highly efficient three-dimensional Cd1-xZnxS photocatalysts
      for visible light photocatalytic water splitting.
AB  - Visible light accounts for about 43% of the solar spectrum, and developing highly
      efficient visible-light-driven photocatalyst is of special significance. In this
      work, highly efficient three-dimensional (3D) Cd1-xZnxS photocatalysts for
      hydrogen generation under the irradiation of visible light were synthesized via
      one-step solvothermal pathway. Scanning electron microscope, X-ray
      diffractometer, Raman spectrometer, and X-ray photoelectron spectrometer were
      utilized to characterize the morphology, crystal structure, vibrational states,
      and surface composition of the obtained 3D Cd1-xZnxS. UV-Vis spectra indicated
      that the as-synthesized Cd1-xZnxS had appropriate bandgap and position of the
      conduction band that is beneficial for visible light absorption and photo
      generated electron-hole pair separation. Moreover, the 3D structure offers a
      larger surface area thus supplying more surface reaction sites and better charge
      transport environment, and therefore, the efficiency of water splitting was
      improved further. 

PMID- 23883430
TI  - Designing a multifaceted survivorship care plan to meet the information and
      communication needs of breast cancer patients and their family physicians:
      results of a qualitative pilot study.
AB  - BACKGROUND: Following the completion of treatment and as they enter the follow-up
      phase, breast cancer patients (BCPs) often recount feeling 'lost in transition',
      and are left with many questions concerning how their ongoing care and monitoring
      for recurrence will be managed. Family physicians (FPs) also frequently report
      feeling ill-equipped to provide follow-up care to BCPs. In this three-phase
      qualitative pilot study we designed, implemented and evaluated a multi-faceted
      survivorship care plan (SCP) to address the information needs of BCPs at our
      facility and of their FPs. METHODS: In Phase 1 focus groups and individual
      interviews were conducted with 35 participants from three stakeholder groups
      (BCPs, FPs and oncology specialist health care providers (OHCPs)), to identify
      specific information needs. An SCP was then designed based on these findings,
      consisting of both web-based and paper-based tools (Phase 2). For Phase 3, both
      sets of tools were subsequently evaluated via focus groups and interviews with 26
      participants. Interviews and focus groups were audio taped, transcribed and
      content analysed for emergent themes and patterns. RESULTS: In Phase 1 patients
      commented that web-based, paper-based and human resources components were
      desirable in any SCP. Patients did not focus exclusively on the post-treatment
      period, but instead spoke of evolving needs throughout their cancer journey. FPs
      indicated that any tools to support them must distill important information in a
      user-friendly format. In Phase 2, a pilot SCP was subsequently designed,
      consisting of both web-based and paper-based materials tailored specifically to
      the needs of BCPs as well as FPs. During Phase 3 (evaluation) BCPs indicated that
      the SCP was effective at addressing many of their needs, and offered suggestions
      for future improvements. Both patients and FPs found the pilot SCP to be an
      improvement from the previous standard of care. Patients perceived the quality of
      the BCP-FP relationship as integral to their comfort with FPs assuming follow-up
      responsibilities. CONCLUSIONS: This pilot multi-component SCP shows promise in
      addressing the information needs of BCPs and the FPs who care for them. Next
      steps include refinement of the different SCP components, further evaluation
      (including usability testing), and planning for more extensive implementation.

PMID- 23883432
TI  - Secondary metabolites of the sponge-derived fungus Acremonium persicinum.
AB  - This study reports the isolation and characterization of six new acremine
      metabolites, 5-chloroacremine A (4), 5-chloroacremine H (5), and acremines O (6),
      P (7), Q (8), and R (9), together with the known acremines A (1), F (2), and N
      (3) from the fungus Acremonium persicinum cultured from the marine sponge
      Anomoianthella rubra. The relative configuration of acremine F (2) was determined
      by analyses of proton coupling constant values and NOESY data, and the absolute
      configuration confirmed as (1S, 4S, 6R) by X-ray crystallographic analysis of the
      borate ester derivative 15. Acremines O, P, and R were each shown to be of 8R
      configuration by 1H NMR analyses of MPA esters. The relative configurations
      suggested for acremines P and Q were each deduced by molecular modeling together
      with NOESY and coupling constant data. The 3J(H-C) values in acremine P were
      measured using the pulse sequence EXSIDE, and the observed 3J(H8-C4) of 5.4 Hz
      and small 3J(H-C) values (<1.5 Hz) from H-8 to C-10 and C-11 were fully
      consistent with stereoisomer 7a. For acremine Q, NOESY data combined with
      molecular modeling established the preferred diastereomer 8a.

PMID- 23883431
TI  - Preliminary evaluation of a robotic apparatus for the analysis of passive
      glenohumeral joint kinematics.
AB  - BACKGROUND: The shoulder has the greatest range of motion of any joint in the
      human body. This is due, in part, to the complex interplay between the
      glenohumeral (GH) joint and the scapulothoracic (ST) articulation. Currently, our
      ability to study shoulder kinematics is limited, because existing models isolate
      the GH joint and rely on manual manipulation to create motion, and have low
      reproducibility. Similarly, most established techniques track shoulder motion
      discontinuously with limited accuracy. METHODS: To overcome these problems, we
      have designed a novel system in which the shoulder girdle is studied intact,
      incorporating both GH and ST motions. In this system, highly reproducible
      trajectories are created using a robotic actuator to control the intact shoulder
      girdle. High-speed cameras are employed to track retroreflective bone markers
      continuously. RESULTS: We evaluated this automated system's capacity to
      reproducibly capture GH translation in intact and pathologic shoulder conditions.
      A pair of shoulders (left and right) were tested during forward elevation at
      baseline, with a winged scapula, and after creation of a full thickness
      supraspinatus tear. DISCUSSION: The system detected differences in GH
      translations as small as 0.5 mm between different conditions. For each, three
      consecutive trials were performed and demonstrated high reproducibility and high
      precision.

PMID- 23883433
TI  - Lentiviral vector mediated delivery of RHBDD1 shRNA down regulated the
      proliferation of human glioblastoma cells.
AB  - Rhomboid domain containing 1 (RHBDD1) gene, a new member of rhomboid family of
      proteins is highly responsible for the regulation of apoptosis by cleaving pro
      apoptotic Bcl-2 family protein BIK. Therefore, the higher expression levels of
      RHBDD1 in cancer tissues may have a direct influence on cancer progression by
      arresting apoptosis. With this background this study was focused to find out the
      effect of RHBDD1 silencing on the progression of human brain glioblastoma cells,
      U251 and U87MG. The results indicated that both cell lines show a higher
      expression level of RHBDD1 and RNA interference (RNA) mediated gene silencing
      successfully down regulated the RHBDD1 gene expression. As a result of RHBDD1
      silencing the proliferation of both cell types was reduced by over 50%, 5 days
      after silencing. Moreover the colony formation was completely inhibited and there
      were no cells present following two week RHBDD1 gene silencing. The cell
      proliferation was inhibited as a result of cell cycle arrest due to RHBDD1
      absence. Therefore, these results clearly indicate that, RHBDD1 is essential for
      the progression of glioblastoma cells and silencing of it is resulting in
      significant inhibition of cell cycle progression and cell proliferation.
      Collectively, this study shows that RHBDD1 gene engineering could be used as an
      effective tool in malignant brain tumor therapy. 

PMID- 23883435
TI  - Omalizumab is effective in treating severe asthma in patients with severe
      cardiovascular complications and its effects on sCD200, d-dimer, CXCL8, 25
      hydroxyvitamin D and IL-1beta levels.
AB  - BACKGROUND: There have been concerns about the cardiovascular safety of
      omalizumab. OBJECTIVES: In this study, the clinical status of the omalizumab
      receiving severe asthma patients and the cytokine expressions patterns were
      investigated. MATERIALS AND METHODS: In a pilot study described below we examined
      the levels of serum eosinophil cationic peptid (ECP), CD200, d-dimer, 25
      hydroxyvitamin D (25(OH)D), CXCL8 and IL-1beta in asthma patients treated with
      anti-IgE therapy, to explore their relationship with disease activity, and the
      impact of anti-IgE therapy impact on those levels. Exercise stress testing and
      blood samples were taken at all follow up visits from the time of first diagnosis
      and after 20 months of treatment during the disease remission. RESULTS:
      Fractional exhaled nitric oxide concentrations and serum levels of sTRAIL,
      sCD200, D-dimer, ECP, total IgE, IL-1beta and Hs-CRP were decreased while CXCL8,
      25(OH)D were increased after starting the treatment of anti-IgE. Our first case
      of a patient, who had both protein C and S deficiency and hence a high risk for
      thromboembolism, documents for the first time the safety of omalizumab for
      asthmatic patients with concurrent risk factors contributing to arteriothrombotic
      events. CONCLUSION: Omalizumab might be used carefully in patients with
      cardiovascular diseases.

PMID- 23883434
TI  - Osteopontin genetic variants are associated with overall survival in advanced non
      small-cell lung cancer patients and bone metastasis.
AB  - PURPOSE: Osteopontin (OPN) plays important roles in the modulation of apoptosis,
      angiogenesis, immune response, and tumor invasion. Elevated osteopontin
      expression has been reported in the lung cancer tissues compared to counterpart
      normal tissues. This study examined whether genetic variations in the osteopontin
      gene are associated with survival of lung cancer patients and occurrence rate of
      bone metastasis. EXPERIMENTAL DESIGN: Three hundred and sixty patients with
      stages I to IV between 2003 and 2007 were recruited in this study and same number
      of healthy persons were used as control. Three promoter osteopontin
      polymorphisms, OPN-66 T/G, -156G/GG, and -443C/T variants were genotyped using
      DNA from blood lymphocytes. Chi-square test and a Fisher's exact test were used
      to analyze the genotype distribution among TNM stages and incidence of bone
      metastasis and lymph mode metastasis. Kaplan-Meier method and log-rank test were
      used to compare survival by different genotypes. RESULTS: For the variant at nt 
      443 (CC), there was a significant difference between the number of patients with
      stage IV and those with all other stages of lung cancer (p < 0.01). Patients with
      -443 (CC) variant had significant higher incidence of bone metastasis development
      compared to other genotypes. For the variant at nt -443 (CT), there was a
      significant difference between the number of lung cancer patients with stage III
      + IV and those with stage I + II (P < 0.01). The survival rates for patients with
      the C/C genotype were significantly lower than for patients with the other two
      genotypes (C/T, T/T). CONCLUSION: OSTEOPONTIN -443C/T polymorphism is a potential
      predictive marker of survival in lung cancer patients, it is correlated with bone
      metastasis significantly.

PMID- 23883436
TI  - Genetic and epigenetic analysis of putative breast cancer stem cell models.
AB  - BACKGROUND: Cancer stem cell model hypothesizes existence of a small proportion
      of tumor cells capable of sustaining tumor formation, self-renewal and
      differentiation. In breast cancer, these cells were found to be associated with
      CD44+CD24-low and ALDH+ phenotype. Our study was performed to evaluate the
      suitability of current approaches for breast cancer stem cell analyses to
      evaluate heterogeneity of breast cancer cells through their extensive genetic and
      epigenetic characterization. METHODS: Breast cancer cell lines MCF7 and SUM159
      were cultured in adherent conditions and as mammospheres. Flow cytometry sorting
      for CD44, CD24 and ALDH was performed. Sorted and unsorted populations,
      mammospheres and adherent cell cultures were subjected to DNA profiling by array
      CGH and methylation profiling by Epitect Methyl qPCR array. Methylation status of
      selected genes was further evaluated by pyrosequencing. Functional impact of
      methylation was evaluated by mRNA analysis for selected genes. RESULTS: Array CGH
      did not reveal any genomic differences. In contrast, putative breast cancer stem
      cells showed altered methylation levels of several genes compared to parental
      tumor cells. CONCLUSIONS: Our results underpin the hypothesis that epigenetic
      mechanisms seem to play a major role in the regulation of CSCs. However, it is
      also clear that more efficient methods for CSC enrichment are needed. This work
      underscores requirement of additional approaches to reveal heterogeneity within
      breast cancer.

PMID- 23883437
TI  - Fabry_CEP: a tool to identify Fabry mutations responsive to pharmacological
      chaperones.
AB  - Fabry_CEP is a user-friendly web-application designed to help clinicians Choose
      Eligible Patients for the therapy with pharmacological chaperones. It provides a
      database and a predictive tool to evaluate the responsiveness of lysosomal alpha
      galactosidase mutants to a small molecule drug, namely 1-Deoxy
      galactonojirimycin. The user can introduce any missense/nonsense mutation in the
      coding sequence, learn whether it is has been tested and gain access to
      appropriate reference literature. In the absence of experimental data structural,
      functional and evolutionary analysis provides a prediction and the probability
      that a given mutation is responsive to the drug. 

PMID- 23883438
TI  - Diarrhoea in the ICU: respective contribution of feeding and antibiotics.
AB  - INTRODUCTION: Diarrhoea is frequently reported in the ICU. Little is known about
      diarrhoea incidence and the role of the different risk factors alone or in
      combination. This prospective observational study aims at determining diarrhoea
      incidence and risk factors in the first 2 weeks of ICU stay, focusing on the
      respective contribution of feeding, antibiotics, and antifungal drugs. METHODS:
      Out of 422 patients consecutively admitted into a mixed medical-surgical ICU
      during a 2-month period, 278 patients were included according to the following
      criteria: ICU stay >24 hours, no admission diagnosis of gastrointestinal
      bleeding, and absence of enterostomy or colostomy. Diarrhoea was defined as at
      least three liquid stools per day. Diarrhoea episodes occurring during the first
      day in the ICU, related to the use of laxative drugs or Clostridium difficile
      infection, were not analysed. Multivariate and stratified analyses were performed
      to determine diarrhoea risk factors, and the impact of the combination of enteral
      nutrition (EN) with antibiotics or antifungal drugs. RESULTS: A total of 1,595
      patient-days were analysed. Diarrhoea was observed in 38 patients (14%) and on 83
      patient-days (incidence rate: 5.2 per 100 patient-days). The median day of
      diarrhoea onset was the sixth day, and 89% of patients had <=4 diarrhoea days.
      The incidence of C. difficile infection was 0.7%. Diarrhoea risk factors were EN
      covering >60% of energy target (relative risk = 1.75 (1.02 to 3.01)), antibiotics
      (relative risk = 3.64 (1.26 to 10.51)) and antifungal drugs (relative risk = 2.79
      (1.16 to 6.70)). EN delivery per se was not a diarrhoea risk factor. In patients
      receiving >60% of energy target by EN, diarrhoea risk was increased by the
      presence of antibiotics (relative risk = 4.8 (2.1 to 13.7)) or antifungal drugs
      (relative risk = 5.0 (2.8 to 8.7)). CONCLUSION: Diarrhoea incidence during the
      first 2 weeks in a mixed population of patients in a tertiary ICU is 14%.
      Diarrhoea risk factors are EN covering >60% of energy target, use of antibiotics,
      and use of antifungal drugs. The combination of EN covering >60% of energy target
      with antibiotics or antifungal drugs increases the incidence of diarrhoea.

PMID- 23883440
TI  - Environmental behavior of the chiral organophosphorus insecticide acephate and
      its chiral metabolite methamidophos: enantioselective transformation and
      degradation in soils.
AB  - Acephate is a widely used organophosphorus insecticide globally, although there
      are some concerns about its usage with regard to acute consumer exposure and side
      effects on nontarget organisms. These concerns are always attributed to the
      acephate metabolite methamidophos. In the many reports about the environmental
      behavior of acephate and its metabolite, none pay any attention to the chirality
      of them. In this study, the enantiomeric transformation and degradation of
      acephate was investigated in three soils under laboratory conditions using
      enantioselective GC-MS/MS. Racemic and enantiopure compounds were incubated in
      separate experiments. The degradation of racemates was shown to be
      enantioselective in unsterilized soils but not in the sterilized soils, thus
      confirming the enantioselectivity was microbially based. The priority of
      enantiomer degradation and transformation varied among soils and racemates. R-(+)
      methamidophos was enriched in the Zhengzhou soil, but degraded faster in the
      Changchun and Nanchang soils than its antipode. For acephate, the Nanchang soil
      enriched R-(+)-acephate, and S-(-)-acephate accumulated in the other two soils.
      Acephate and methamidophos were both configurationally stable in soil, showing no
      interconversion of R-(+)- to S-(-)-enantiomers, or vice versa. The conversion of
      acephate to methamidophos proceeded with retention of configuration. Generally,
      the degradation followed approximate first-order kinetics, but showed significant
      lag phases. 

PMID- 23883441
TI  - The GluN3A subunit exerts a neuroprotective effect in brain ischemia and the
      hypoxia process.
AB  - NMDARs (N-methyl-D-aspartate receptors) mediate the predominantly excitatory
      neurotransmission in the CNS (central nervous system). Excessive release of
      glutamate and overactivation of NMDARs during brain ischemia and the hypoxia
      process are causally linked to excitotoxicity and neuronal damage. GluN3
      subunits, the third member of the NMDAR family with two isoforms, GluN3A and
      GluN3B, have been confirmed to display an inhibitory effect on NMDAR activity.
      However, the effect of GluN3 subunits in brain ischemia and hypoxia is not
      clearly understood. In the present study, the influence of ischemia and hypoxia
      on GluN3 subunit expression was observed by using the 2VO (two-vessel occlusion)
      rat brain ischemia model and cell OGD (oxygen and glucose deprivation) hypoxia
      model. It was found that GluN3A protein expression in rat hippocampus and the
      prefrontal cortex was increased quickly after brain ischemia and remained at a
      high level for at least 24 h. However, the expression of the GluN3B subunit was
      not remarkably changed in both the animal and cell models. After OGD exposure,
      rat hippocampal neurons with GluN3A subunit overexpression displayed more
      viability than the wild-type neurons. NG108-15 cells overexpressing GluN3A
      presented pronounced resistance to glutamate insult. Blocking the increase of
      intracellular Ca2+ concentration may underlie the neuroprotective mechanism of up
      regulated GluN3A subunit. Suppressing the generation of hydroxyl radicals and NO
      (nitric oxide) is probably also involved in the neuroprotection. 

PMID- 23883442
TI  - Acquisition of the polarity sensitive item renhe 'any' in Mandarin Chinese.
AB  - The present study investigated Mandarin-speaking children's acquisition of the
      polarity sensitive item renhe 'any' in Mandarin Chinese. Like its English
      counterpart any, renhe can be used as a negative polarity item (NPI), or as a
      free choice (FC) item, and both the distribution and interpretation of renhe are
      governed by the same syntactic and semantic constraints as English any. Using a
      Truth Value Judgment Task, the present study tested five-year-old Mandarin
      speaking children's comprehension of FC renhe in sentences containing the modal
      word neng 'can', and tested children's comprehension of NPI renhe in sentences
      containing the temporal conjunction zai...zhiqian 'before'. Most children
      demonstrated knowledge of the interpretation of both FC renhe and NPI renhe
      despite a paucity of relevant adult input. Like adults, however, Mandarin
      speaking children do not use renhe frequently in ordinary conversation, due to
      the availability of alternative colloquial expressions (wh-pronouns) that also
      convey children's intended meanings.

PMID- 23883443
TI  - Encapsulation of clay within polymer particles in a high-solids content aqueous
      dispersion.
AB  - By using a two-step polymerization process, it was possible to encapsulate clay
      platelets within polymer particles dispersed in water. First, seed polymer
      particles with chemically bonded clay were obtained by batch miniemulsion
      polymerization. Then, the clay was buried within the particles by the addition of
      neat monomer in a second step. The final stable dispersions can have a solids
      content of up to 50 wt %. Transmission electron microscopy images clearly show
      the presence of clay platelets inside the polymer colloids, although they are not
      totally exfoliated. The obtained nanocomposites showed an increase in both the
      storage modulus in the rubbery state and the water resistance as the clay content
      increases. The approach presented here might be useful for encapsulating other
      high-aspect ratio nanofillers. 

PMID- 23883444
TI  - pi donation and its effects on the excited-state lifetimes of luminescent
      platinum(II) terpyridine complexes in solution.
AB  - Introducing electron-donating groups extends the excited-state lifetimes of
      platinum(II)-terpyridine complexes in fluid solution. Such systems are of
      interest for a variety of applications, viz., as DNA-binding agents or as
      components in luminescence-based devices, especially sensors. The complexes
      investigated here are of the form [Pt(4'-X-T)Y](+), where 4'-X-T denotes a 4'
      substituted 2,2':6',2"-terpyridine ligand and Y denotes the coligand. The pi
      donating abilities of -X and -Y increase systematically in the orders -NHMe < 
      NMe2 < -(pyrrolidin-1-yl) and -CN < -Cl < -CCPh, respectively. The results
      presented include crystal structures of two new 4'-NHMe-T complexes of platinum,
      as well as absorption, emission, and excited-state lifetime data for nine
      complexes. Excited-state lifetimes obtained in deoxygenated dichloromethane vary
      by a factor of 100, ranging from 24 MUs for [Pt(4'-pyrr-T)CN](+) to 0.24 MUs for
      [Pt(4'-ma-T)Cl](+), where ma-T denotes 4'-(methylamino)-2,2':6',2"-terpyridine
      and pyrr-T denotes 4'-(pyrrolidin-1-yl)-2,2':6',2"-terpyridine. Analysis of
      experimental and computational results shows that introducing a simple amine
      group on the terpyridine and/or a pi-donating coligand engenders the emitting
      state with intraligand charge-transfer (ILCT) and/or ligand-ligand charge
      transfer (LLCT) character. The excited-state lifetime increases when the change
      in orbital parentage lowers the emission energy, suppresses quenching via d-d
      states, and encourages delocalization of the excitation onto the ligand(s). At
      some point, however, the energy is low enough that direct vibronic coupling to
      the ground-state surface becomes important, and the lifetime begins to decrease
      again. 

PMID- 23883445
TI  - Making nutrition work for development.

PMID- 23883446
TI  - The year 2013: nutrition at the top of the global agenda.

PMID- 23883447
TI  - Pre-hospital advanced airway management by experienced anaesthesiologists: a
      prospective descriptive study.
AB  - INTRODUCTION: We report data from the first Utstein-style study of physician
      provided pre-hospital advanced airway management. MATERIALS AND METHODS:
      Anaesthesiologists from eight pre-hospital critical care teams in the Central
      Denmark Region (a mixed rural and urban region with 1.27 million inhabitants)
      prospectively registered data according to the template for reporting data from
      pre-hospital advanced airway management. Data collection took place from February
      1st 2011 to October 31st 2012. Included were patients of all ages on whom pre
      hospital advanced airway management was performed. The objective was to estimate
      the incidences of failed and difficult pre-hospital endotracheal intubation, and
      complications related to pre-hospital advanced airway management. RESULTS: The
      overall incidence of successful pre-hospital endotracheal intubation among 636
      intubation attempts was 99.7%, even though 22.4% of pre-hospital endotracheal
      intubations required more than one intubation attempt. The overall incidence of
      complications related to pre-hospital advanced airway management was 7.9%.
      Following rapid sequence intubation, the incidence of first pass success was
      85.8%, the overall incidence of complications was 22.0%, the incidence of
      hypotension 7.3% and that of hypoxia 5.3%. Multiple endotracheal intubation
      attempts were associated with an increased overall incidence of complications. No
      airway management related deaths occurred. DISCUSSION: The overall incidence of
      successful pre-hospital endotracheal intubations compares to those found in other
      physician-staffed pre-hospital systems. The incidence of pre-hospital
      endotracheal intubations requiring more than one attempt is higher than
      suspected. The incidence of hypotension or hypoxia after pre-hospital rapid
      sequence intubation compares to those found in UK emergency departments.
      CONCLUSION: Pre-hospital advanced airway management including pre-hospital
      endotracheal intubation performed by experienced anaesthesiologists is associated
      with high success rates and relatively low incidences of complications. An
      increased first pass success rate following pre-hospital endotracheal intubation
      may further reduce the incidence of complications and enhance patient safety in
      our system.

PMID- 23883449
TI  - [Medical publications and information technologies].
AB  - The development of the computer science during the last 30 years has had a very
      important influence in human life, changing paradigms on all daily activities
      like public policies, commerce, education and science development. The aim of
      this editorial is to communicate some considerations about the way the
      development of technology in information and communication had influenced on the
      spread of scientific knowledge in its using on medical publications. 

PMID- 23883448
TI  - Low-grade albuminuria is associated with early but not late carotid
      atherosclerotic lesions in community-based patients with type 2 diabetes.
AB  - BACKGROUND: Low-grade albuminuria is associated with cardiovascular risk factors
      and mortality. Our aim was to investigate the association between low-grade
      albuminuria and carotid atherosclerotic lesions in community-based patients with
      type 2 diabetes. METHODS: A cross-sectional study was performed in 475 community
      based patients with type 2 diabetes (190 males and 285 females) with normal
      urinary albumin-to-creatinine ratios (UACR) (< 3.5 mg/mmol) from Shanghai, China.
      The subjects were stratified into tertiles based on UACR levels (the lowest
      tertile was UACR <= 1.19 mg/mmol, and the highest tertile was UACR >= 2 mg/mmol).
      Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation
      and stenosis were assessed and compared among the three groups based on
      ultrasonography. The urinary albumin excretion rate was determined as the mean of
      the values obtained from three separate early morning urine samples. RESULTS:
      Compared with the subjects with UACR in the lowest tertile, the subjects with
      UACR in the middle and highest tertiles had greater CIMT values (0.88 +/- 0.35
      mm, 0.99 +/- 0.43 mm and 1.04 +/- 0.35 mm, respectively; all p < 0.05) and a
      higher prevalence of carotid atherosclerotic plaques (25.3%, 39.0% and 46.2%,
      respectively; all p < 0.05) after adjusting for sex and age. Fully adjusted
      multiple linear regression and logistic regression analyses revealed that UACR
      tertiles were significantly associated with elevated CIMT (p = 0.007) and that,
      compared with the subjects in the first tertile of UACR, those in the second and
      third tertiles had 1.878- and 2.028-fold risk of carotid plaques, respectively.
      However, there was no statistical association between UACR tertile and the
      prevalence of carotid stenosis. CONCLUSIONS: Higher UACR within the normal range
      was independently associated with early but not late carotid atherosclerotic
      lesions in community-based patients with type 2 diabetes. Low-grade albuminuria
      contributes to the risk of carotid atherosclerosis and may be used as an early
      marker for the detection of atherosclerosis in patients with type 2 diabetes.

PMID- 23883450
TI  - [Influenza: a disease that is changing the world].

PMID- 23883451
TI  - [Considerations about the pneumology in Mexico].

PMID- 23883452
TI  - [Impact of an educational institutional program in the control of the diabetic
      patient].
AB  - OBJECTIVE: to assess the impact of an educational institutional program in the
      control of type 2 diabetic patient. METHODS: intervention educational study, with
      quasi-experimental and self-controlled subjects. A convenience non-probabilistic
      sample was used including 151 patients from the program for the integral care of
      diabetic patients. Demographic variables: gender, age, type of insurance,
      somatometric and metabolic profile. The assistance to a one-year length,
      educational program was necessary. Descriptive and inferential parametric
      statistics were used. RESULTS: 106 women and 45 men, with age range between 15
      and 87 years, and with an average of 57.22 +/- 11.47, were studied. A significant
      decrease in body mass index, waist circumference, venous glucose fasting and post
      prandial values, cholesterol, systolic blood pressure, triglycerides and
      glycosylated hemoglobin (t Student semi-detached, p < 0.05) was observed. There
      were no changes in diastolic blood pressure (p = 0.334). CONCLUSIONS: one year
      afterwards, the strategy based on education for the control of the diabetic
      patient shown a favorable pattern in most of somatometric and metabolic
      parameters. We suggest to extend this study over a longer period to determine if
      the effects persist over time.

PMID- 23883453
TI  - [Obesity, a main risk factor for endometrial cancer].
AB  - BACKGROUND: obesity is a well-known risk factor for endometrial cancer, and both
      diseases are rising in Mexico. However, in our country some data indicates low
      influence of obesity on this neoplasm, and this is contradictory. Therefore, we
      explore the prevalence of obesity on women affected with this malignant tumor.
      METHODS: this was a pilot case-control study in a general hospital at Mexico
      City. The analysis involved obesity (a body mass index >= 30 kg/m(2)) diabetes
      mellitus and systemic arterial hypertension. RESULTS: the sample was of 66 women:
      22 cases and 44 controls. In cases, obesity occurred in 77 % (odds ratio [OR]
      8.1, 95 % confidence interval [CI] 2.46-26.6); diabetes mellitus in 41 % (OR 4.3,
      CI 1.31-14.7); and systemic arterial hypertension in 41 % (OR 2.3, CI 0.78-7.1).
      CONCLUSIONS: these preliminary results suggested that obesity was the most
      frequent risk factor for these women with endometrial cancer.

PMID- 23883454
TI  - [Environmental UV radiation levels for dosing PUVA-sol in Mexico].
AB  - BACKGROUND: PUVA-sol therapy has the advantage of its extensive availability and
      low cost. However, its use is empirical. The aim was to quantify the
      environmental UVA radiation and suggest a method for PUVA-sol administration.
      METHODS: we measured the UV radiation in the center of Mexico (22  degrees N, 101
      degrees W, 1877 m) by means of terrestrial radiometry from 2007 to 2011. We
      registered the variations according to hour, month, cloudiness and transmission
      through domestic silicate plates. RESULTS: more than 75 % of the UVA radiation is
      registered between the hours of 9:00 and 17:00. The annual lowest average
      intensity was 20 mW/cm(2) and the highest 25.4 mW/cm(2) (ANOVA, p < 0.001). The
      monthly UVA irradiation during the zenith for clear skies can be estimated by the
      following formula: 23.8 + 0.13 (month) - 0.13 (month - 6.5)(2), (r(2) = 0.95, p <
      0.001). The commonly used silicate plate (3 mm) has a UVB absorbance of 0.93, and
      UVA transmittance of 0.58. CONCLUSIONS: the rational use of PUVA-sol is possible
      on the basis of the obtained data. It is necessary to isolate UVB radiation, and
      to adjust exposure during cloudy days, as well as following the safety protocol
      to obtain benefit and to reduce the risk of adverse effects.

PMID- 23883455
TI  - [Male hormonal profile in workers exposed to toluene in an industrial packaging
      plant].
AB  - OBJECTIVE: to identify changes in the male hormonal profile (MHP), consisting of
      luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone, in
      workers exposed to toluene. METHODS: cross-sectional study that included 42
      workers, formed in two groups: with high and low exposure to toluene (HET and
      LET, respectively); the hippuric acid in urine, and the serum concentration in
      FSH, LH, and testosterone were measured. RESULTS: hippuric acid in subjects with
      LET was 2.53 +/- 1.20 g/g creatinine, and with HET: 6.31 +/- 3.83 g/g creatinine
      (p = 0.02). Seric FSH concentration was 5.12 +/- 0.77 and 3.55 +/- 0.3 mU/mL (p =
      0.02) in LET and HET, respectively; LH: 2.66 +/- 0.45 and 2.77 +/- 0.21 (p =
      0.81), and testosterone 3.91 +/- 0.34 and 4.86 +/- 0.23 ng/mL (p = 0.04). By
      regression analysis, the correlation coefficient of FSH with hippuric acid was r
      = -0.33 (p = 0.031), with coefficient of determination of 11 %; the LH
      correlation coefficient was r = -0.037 (p = 0.88) and 0.05 %, respectively; and
      the one for testosterone was r = 0.61 (p = 0.0001) and 34 %. CONCLUSIONS: in HET
      group, FSH and LH serum levels diminished; testosterone shows an opposite
      response, perhaps explained by a different sensitivity of the male gonads exposed
      to toluene.

PMID- 23883456
TI  - [Demographic factors and comorbidity associated to prehypertension].
AB  - BACKGROUND: prehypertension is the category established in JNC-7, which
      designates the individuals that present diastolic blood pressure of 80-89 mm Hg
      and systolic blood pressure of 120-139 mm Hg, and it is associated to high rates
      of cardiovascular disease. The purpose of the study was to identify prevalence
      rates and their correlation with sociodemographic factors and comorbidity in a
      sample of a population of Veracruz, Mexico. METHODS: a cross-sectional and
      representative survey was chosen by means of probability sampling.
      Sociodemographic factors, lifestyle and anthropometric characteristics were
      assessed. Odds ratios and 95 % confidence intervals were obtained. RESULTS: the
      prehypertension prevalence found was 33.8 %, with an average age of 40.9 +/- 14.2
      years in prehypertensive subjects, and 50.6 +/- 12.7 in hypertension subjects (p
      < 0.05). In relation with prehypertension, males presented a 1.48 (1.18-1.86) OR.
      Also, those who had more than 40 years had an OR of 1.9 (1.51-2.38); the ones
      with basic schooling, an OR of 1.73 (1.38-2.17); subjects with hyperglycemia, OR
      3.0 (1.5-3.75); with overweight, OR 1.41 (1.01-1.68); and those with other
      comorbidities an OR of 1.61 (1.09-2.36). CONCLUSIONS: a high prevalence of
      prehypertension was found in the sample, and it was associated to male gender
      subjects, aged above 40 years, with basic schooling and relevant comorbidities,
      such as diabetes and cardiovascular disease.

PMID- 23883457
TI  - [Parental perception of their child's pain tolerance and abdominal postoperative
      analgesic requirements].
AB  - OBJECTIVE: to determine if a child's pain tolerance as perceived by their parents
      could predict the difficulty of a child's post-abdominal surgery pain control.
      METHODS: a prospective cohort study; children (3 to 16 years old) perceived as
      tolerant (PT) and non-tolerant to pain (NoPT). The analgesic plan was decided by
      their surgeons. We analyzed the level of pain (through Wong-Baker facial pain
      scale) and analgesic requirements (drug, dose modifications) immediately after
      recovery from anesthesia, 24 and 48 hours later. RESULTS: 62 patients were
      evaluated (34 PT and 28 NoPT). Since the recovery NoPT children requested more
      analgesics (42.9 % versus 2.9 %, p < 0.001) and higher doses. At 24 hours,
      although 87 % received analgesia, NoTP children required extra doses (50 % versus
      23.5 % PT, p = 0.03). After 48 hours, 83 % (PT) and 72 % (NoPT) kept receiving
      analgesia (p = 0.36) but the NoPT still asked for more rescue doses (46.7 %
      versus 14.7 %, p = 0.01). CONCLUSIONS: it is important to identify children
      perceived as poorly tolerant or not tolerant to pain before a painful procedure,
      in order to plan an efficient strategy for pain control.

PMID- 23883458
TI  - [The current state of obesity in Mexico].
AB  - Excess weight (overweight and obesity) is currently recognized as one of the most
      important challenges of public health in the world, given its size, speed of
      growth, and the negative effect on the population who suffers it. Overweight and
      obesity increases significantly the risk of chronic non-communicable diseases,
      and premature mortality, as well as the social cost of health. Today, Mexico has
      the second global prevalence of obesity in the adult population (30 %), which is
      ten times higher than Korea's or Japan's (4 %). Until 2012, 26 million Mexican
      adults were overweight, and 22 million, obese. This implies a major challenge for
      the health sector. Mexico needs to plan and implement strategies and cost
      effective actions for the prevention and control of obesity in children,
      adolescents, and adults. Global experience shows that proper care of obesity and
      overweight demands to formulate and coordinate efficient multi-sectoral
      strategies for enhancing protective factors to health, particularly to modify
      individual behavior, family and community. 

PMID- 23883459
TI  - [Clinical research XV. From the clinical judgment to the statistical model.
      Difference between means. Student's t test].
AB  - Among the test to show differences between means, the Student t test is the most
      characteristic. Its basic algebraic structure shows the difference between two
      means weighted by their dispersion. In this way, you can estimate the p value and
      the 95 % confidence interval of the mean difference. An essential feature is that
      the variable from which the mean is going to be calculated must have a normal
      distribution. The Student t test is used to compare two unrelated means (compared
      between two maneuvers), this is known as t test for independent samples. It is
      also used to compare two related means (a comparison before and after a maneuver
      in just one group), what is called paired t test. When the comparison is between
      more than two means (three or more dependent means, or three or more independent
      means) an ANOVA test (or an analysis of variance) it is used to perform the
      analysis. 

PMID- 23883460
TI  - [Medical and legal considerations in whiplash injury].
AB  - Whiplash injury usually occurs in people who suffered an automobile accident, but
      also occurs as a result of physical assault and other mechanisms. Diagnosis and
      initial management of the patient by the emergency physician or orthopedist, and
      prescribing indications, are taken into account by two forensic intervention
      specialists. One of these is the medical officer, who, through analysis of the
      injury mechanism, establishes a cause-effect relationship and concludes whether
      the accident suffered by a worker it is related to work or not, determines how
      long the worker will remain disabled and if the injury caused permanent
      disability under Federal Labor Law. The medical examiner by injury classification
      assists the Public Ministry so that it can frame the crime of injury to the
      Criminal Code of Federal District. For these reasons a review of medical
      information about the mechanism of injury, diagnosis, treatment and healing time
      was performed to help both specialists to standardize their approach in their
      daily activities. 

PMID- 23883461
TI  - [Impaired fasting glucose and postprandial glucose intolerance. The role of
      immediate family history].
AB  - OBJECTIVE: to determine the prevalence of impaired fasting glucose (IFG) and
      postprandial glucose intolerance (PGI) in individuals with diabetic parent and
      risk factors for developing DM2. METHODS: a cross-sectional study among 162
      individuals with father or mother with DM2, age from 30 to 35 years with risk
      factors for developing DM2 was performed. Fasting plasma glucose was done, and a
      glucose tolerance curve was taken in those who had IFG. RESULTS: prediabetes was
      found in 9.8 % (16) [of which 43.8 % (7) presented PGI]; and 90.2 % (146) were
      normoglycemic. The mean age in patients with IFG and PGI was 33.5 years and in
      the normoglycemic group was 32.2, t = 8.36, p = 0.004. The mean weight in the IFG
      and PGI group was 72.58 kg and 69.85 kg in normoglycemic group, t = 1.21 and p =
      0.27. Mean BMI, IFG and PGI was 27.78 and in normoglycemic 26.58, t = 5.25, p =
      0.02. CONCLUSIONS: the results suggested that in descents from parents with DM2
      with risk factors we must investigate early prediabetes or IFG with fasting
      plasma glucose.

PMID- 23883462
TI  - [Physical exploration and morbidity of pelvic members in the diabetic patient
      type 2].
AB  - OBJECTIVE: to determine the prevalence of the physical exploration and morbidity
      on pelvic members in the type 2 diabetic patient. METHODOLOGY: cross-sectional
      study; 189 files of diabetic family medicine patients were analyzed. The sample
      was considered with the formula of proportions for a finite population. Sampling
      units were chosen by convenience and they were taken up again from each one of
      the family medicine physician's offices. Sociodemographic variables, pathologies,
      time of evolution of diabetes, glycemic control and consultations along a year
      were studied. Physical explorations were made and signs explored by the
      physicians. Descriptive statistic for the analysis of data was used. RESULTS:
      average age 58.89 years (CI 95 %, 57.1-60.7); women predominated with 61.9 % (CI
      95 %, 55.0-68.8), mean time of evolution 10.60 years +/- 7.29. In 74.1 % some
      sign in pelvic members was explored, and in 14.3 % some added problem was
      detected. Of these, 9 % suffered from onychomycosis. CONCLUSION: physical
      exploration of pelvic members it is not to be performed in all type 2 diabetic
      patients.

PMID- 23883463
TI  - [Lesiones de mucosa bucal. Factores asociados en poblacion infantil].
AB  - BACKGROUND: there are few systematic studies reporting the prevalence of oral
      mucosal lesions in children. The reported prevalence is ranging from 4.1 % to
      52.6 %, probably due to differences in methodology and population. The aim was to
      identify the prevalence of oral mucosal lesions in children population. METHODS:
      a cross, descriptive, retrospective study in children who attended the dental
      clinic San Lorenzo Atemoaya was done (January 2006-July 2009); the data was
      obtained from medical records. Oral mucosal lesions were recorded. Descriptive
      analysis and unconditional logistic regression were conducted. RESULTS: the
      sample was 367; there were 200 males (54.5 %). The median age was six years. The
      prevalence of oral mucosal lesions was 66.2 %. The most common lesions were
      cheilitis simple (41.1 %), melanotic macule (18.3 %), petechiae (16.9 %) and
      traumatic ulcer (12 %), without difference between sexes. The sucking lip was
      associated with cheilitis simple (OR 1.7, p = 0.013) and recurrent ulcers with
      onychophagia (OR 15.75, p = 0.026). CONCLUSIONS: it was observed a higher
      prevalence of oral mucosal lesions in children than reported in other papers.
      Association is confirmed between parafunctional habits and oral mucosal lesions.

PMID- 23883464
TI  - [Overweight, obesity, diabetes, and hypertension in endometrial cancer].
AB  - BACKGROUND: in postmenopausal women, the excess of fat has been associated with
      an increased risk of endometrial cancer. The aim of the study was to determine
      the prevalence of overweight, obesity, diabetes and hypertension in patients with
      endometrial cancer. METHODS: we collected demographic, clinical, laboratory and
      histopathological information from the electronic records of patients diagnosed
      with endometrial cancer in the period from January 2009 to July 2011.
      Subsequently descriptive analysis of the information was done. RESULTS: a total
      of 274 records. The average age of patients was 54 years. The 50.4 % were
      postmenopausal. At the time of diagnosis, 112 cases (48.6 %) were in clinical
      stage I. Of all patients, 104 (37.9 %) had diabetes mellitus, 122 (44.5 %)
      hypertension, 194 (72.6 %) were overweight or obese, and 24 cases were registered
      with the metabolic syndrome. CONCLUSIONS: in regards to this diagnosis the
      results show a higher incidence of overweight and obesity compared with other
      countries. It is necessary to conduct further studies to assess the relationship
      of excess fat as a risk factor for endometrial cancer.

PMID- 23883465
TI  - [DRESS syndrome. A clinical case report].
AB  - BACKGROUND: DRESS syndrome (Drug Reaction with Eosinophilia and Systemic
      Symptoms) or reaction to drugs with eosinophilia and systemic symptoms is a
      serious drug reaction associated with the use of aromatic anticonvulsants and
      allopurinol. At least 44 drugs have been associated with DRESS. The aim was to
      present the case of a patient with DRESS syndrome associated with phenytoin.
      CLINICAL CASE: a 20 year old woman, with a history of seizures since childhood,
      presented generalised tonic-clonic seizures for the last three months. Therefore,
      she began treatment with 100 mg of phenytoin, administered orally, every 8 hours.
      Three weeks later, she developed fever up to 42 degrees, papules in the hands
      extending to trunk and extremities, generalized rubicund, pruritus, pain while
      urinating, adding hyperoxia, dysphagia and dry cough. Consequently, she went to
      the emergency room. DISCUSSION: the diagnosis is clinical and it is set according
      to the criteria of the scale of RegiSCAR. As the initial manifestations are
      unspecific, the diagnosis and treatment could be delayed. The importance of
      recognizing this syndrome is an early treatment to get better prognostics. The
      mortality is up to 10 %.

PMID- 23883466
TI  - [Early diagnostic accuracy of the O'Sullivan test in gestational diabetes].
AB  - OBJECTIVE: to assess the specificity and sensibility of the O'Sullivan test for
      gestational diabetes in early pregnancy. METHODS: a pilot study in 50 women with
      low-risk of pregnancy, without history of alteration of glucose was done. The
      O'Sullivan test consisted in the administration of 50 g of glucose; glycemia was
      measured 60 minutes after, between weeks 14 and 23 and between weeks 24 and 28 of
      pregnancy. Value was considered positive with a glycemia = 140 mg/dL. We
      calculated sensitivity, specificity and predictive values. RESULTS: O'Sullivan
      test performed between weeks 14 and 23 was positive in three pregnant women (6
      %), and between weeks 24 and 28, in four (8 %); there was no statistical
      difference in both measurements (p > 0.05). The sensitivity was 75 % (95 %, CI
      30.1 % to 95.4 %), and the specificity 100.0 % (95 %, CI 92.3 % to 100 %).
      CONCLUSIONS: the O'Sullivan test performed between weeks 14 and 23 of gestation
      showed good sensitivity and specificity in the diagnosis of early gestational
      pregnancy.

PMID- 23883467
TI  - [Neuropathic Gaucher disease treated with long enzyme replacement therapy. Two
      clinical cases].
AB  - Gaucher disease (GD) is the most common of all inherited lipid storage diseases.
      It is an autosomal recessive disorder portraying catabolism and cerebroside
      deposit in the lysosomes, which is due to a lack of glucocerebrosidase enzyme.
      Though GD shows a panethnic pattern of presentation, it particularly affects the
      Ashkenazi Jewish population. Several mutations have been defined among GD
      patients, and some genotypes related to neurologic affection have been described
      (L444P--most common mutation for neuropathic GD--188S, V394L and G377S). Lipid
      material storage or deposit exerts multiorganic affection. Enzyme replacement
      therapy (ERT) has demonstrable efficacy in reversing organic damage related to
      GD, though its capability to stop neurologic affection is currently under
      controversy and particular research. This paper portrays two GD cases of Mexican
      children treated with ERT at general zone hospitals of the Instituto Mexicano del
      Seguro Social in recent years, both of them depicting characteristic type 3 GD
      mutations, and comparing their clinical evolution with and without neurological
      features.

PMID- 23883469
TI  - [In memory of Carlos Mac Gregor].

PMID- 23883468
TI  - [Practice clinical guideline. Prevention, diagnosis and treatment of overweight
      and obesity].
AB  - Excess body weight (overweight and obesity) is currently recognized as one of the
      most important challenges of public health in the world, due to its size, speed
      of growth and the negative effect on health. Currently, Mexico and United States
      have the highest prevalence of obesity in the adult population (30 %), which is
      nearly ten times higher than that of Japan or Korea (4 %). In our country, the
      trends of overweight and obesity in different national surveys show steady
      increase in prevalence over time. According to the results of the National Survey
      of Health and Nutrition 2012 (ENSANUT, according to its initials in Spanish), the
      combined prevalence of overweight or obese (BMI = 25 kg/m(2)) in the population
      over 20 years is higher in women (73.0 %) than men (69.4 %), while the prevalence
      of obesity (BMI = 30 kg/m(2)) is almost higher in females than in males. Global
      experience shows that proper care of obesity and overweight requires formulating
      and coordinating comprehensive and efficient multilevel strategies for enhancing
      protective factors to health, particularly to modify individual, family and
      community behavior. It is unlikely that a single intervention can modify the
      incidence or natural history of overweight and obesity.

PMID- 23883470
TI  - [Implications in primary health care of medical genetics and genomic in type 2
      diabetes mellitus].
AB  - Type 2 diabetes mellitus is a complex disease and a global health problem.
      Therefore, the first level of health care should handle the approaches of medical
      genetics and genomics to reduce its incidence. The aim is to present perspectives
      analyzed by our group in two areas of genetics and its clinical application.
      Emphasis is placed on the coexistence of several genetic forms clinically
      detectable in patients with diabetes, missing heritability associated with low
      penetrance, and epigenomics mechanism. It is discussed the effect of genetic
      variation associated with resistance to insulin, beta-cell dysfunction, shaft
      incretin, and other points of interest, such as thrifty genotype hypothesis,
      conformational disease, genetically unknown foods, phenocopies as clinically
      silent hypercortisolism, molecular phytopharmacology in the clinical management.
      Finally, the result was displayed in the Mexican population from genetic studies
      and new findings of clinical importance, such as involvement of melatonin and
      effect of variations in the number of copies in a genomic region. 

PMID- 23883472
TI  - Low-flow CO2 removal integrated into a renal-replacement circuit can reduce
      acidosis and decrease vasopressor requirements.
AB  - INTRODUCTION: Lung-protective ventilation in patients with ARDS and multiorgan
      failure, including renal failure, is often paralleled with a combined respiratory
      and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas
      exchanger integrated into a conventional renal-replacement circuit on CO2
      removal, acidosis, and hemodynamics. METHODS: In ten ventilated critically ill
      patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy,
      effects of low-flow CO2 removal on respiratory acidosis compensation were tested
      by using a hollow-fiber gas exchanger added to the renal-replacement circuit.
      This was an observational study on safety, CO2-removal capacity, effects on pH,
      ventilator settings, and hemodynamics. RESULTS: CO2 elimination in the low-flow
      circuit was safe and was well tolerated by all patients. After 4 hours of
      treatment, a mean reduction of 17.3 mm Hg (-28.1%) pCO2 was observed, in line
      with an increase in pH. In hemodynamically instable patients, low-flow CO2
      elimination was paralleled by hemodynamic improvement, with an average reduction
      of vasopressors of 65% in five of six catecholamine-dependent patients during the
      first 24 hours. CONCLUSIONS: Because no further catheters are needed, besides
      those for renal replacement, the implementation of a hollow-fiber gas exchanger
      in a renal circuit could be an attractive therapeutic tool with only a little
      additional trauma for patients with mild to moderate ARDS undergoing invasive
      ventilation with concomitant respiratory acidosis, as long as no severe
      oxygenation defects indicate ECMO therapy.

PMID- 23883471
TI  - Levels of pro-apoptotic regulator Bad and anti-apoptotic regulator Bcl-xL
      determine the type of the apoptotic logic gate.
AB  - BACKGROUND: Apoptosis is a tightly regulated process: cellular survive-or-die
      decisions cannot be accidental and must be unambiguous. Since the suicide program
      may be initiated in response to numerous stress stimuli, signals transmitted
      through a number of checkpoints have to be eventually integrated. RESULTS: In
      order to analyze possible mechanisms of the integration of multiple pro-apoptotic
      signals, we constructed a simple model of the Bcl-2 family regulatory module. The
      module collects upstream signals and processes them into life-or-death decisions
      by employing interactions between proteins from three subgroups of the Bcl-2
      family: pro-apoptotic multidomain effectors, pro-survival multidomain
      restrainers, and pro-apoptotic single domain BH3-only proteins. Although the
      model is based on ordinary differential equations (ODEs), it demonstrates that
      the Bcl-2 family module behaves akin to a Boolean logic gate of the type
      dependent on levels of BH3-only proteins (represented by Bad) and restrainers
      (represented by Bcl-xL). A low level of pro-apoptotic Bad or a high level of pro
      survival Bcl-xL implies gate AND, which allows for the initiation of apoptosis
      only when two stress stimuli are simultaneously present: the rise of the p53
      killer level and dephosphorylation of kinase Akt. In turn, a high level of Bad or
      a low level of Bcl-xL implies gate OR, for which any of these stimuli suffices
      for apoptosis. CONCLUSIONS: Our study sheds light on possible signal integration
      mechanisms in cells, and spans a bridge between modeling approaches based on ODEs
      and on Boolean logic. In the proposed scheme, logic gates switching results from
      the change of relative abundances of interacting proteins in response to signals
      and involves system bistability. Consequently, the regulatory system may process
      two analogous inputs into a digital survive-or-die decision.

PMID- 23883473
TI  - Differential modulation of human intestinal bifidobacterium populations after
      consumption of a wild blueberry (Vaccinium angustifolium) drink.
AB  - Bifidobacteria are gaining increasing interest as health-promoting bacteria.
      Nonetheless, the genus comprises several species, which can exert different
      effects on human host. Previous studies showed that wild blueberry drink
      consumption could selectively increase intestinal bifidobacteria, suggesting an
      important role for the polyphenols and fiber present in wild blueberries. This
      study evaluated the modulation of the most common and abundant bifidobacterial
      taxonomic groups inhabiting the human gut in the same fecal samples. The analyses
      carried out showed that B. adolescentis, B. breve, B.
      catenulatum/pseudocatelulatum, and B. longum subsp. longum were always present in
      the group of subjects enrolled, whereas B. bifidum and B. longum subsp. infantis
      were not. Furthermore, it was found that the most predominant bifidobacterial
      species were B. longum subsp. longum and B. adolescentis. The results obtained
      revealed a high interindividual variability; however, a significant increase of
      B. longum subsp. infantis cell concentration was observed in the feces of
      volunteers after the wild blueberry drink treatment. This bifidobacterial group
      was shown to possess immunomodulatory abilities and to relieve symptoms and
      promote the regression of several gastrointestinal disorders. Thus, an increased
      cell concentration of B. longum subsp. infantis in the human gut could be
      considered of potential health benefit. In conclusion, wild blueberry consumption
      resulted in a specific bifidogenic effect that could positively affect certain
      populations of bifidobacteria with demonstrated health-promoting properties.

PMID- 23883474
TI  - Evaluation of the toxic effects of municipal wastewater effluent on mice using
      omic approaches.
AB  - Municipal wastewater effluents (MWWE) contain a lot of trace organic pollutants,
      which will be a threat to environmental health. However, little information is
      available for the mixed toxicity of MWWE on mammals. In the present study, male
      mice were exposed to MWWE for 90 days, and then, histopathology and clinical
      biochemistry determination and transcriptomic and metabolomic profiling were
      conducted. The results showed that MWWE exposure resulted in injuries in liver
      and kidney. Combined transcriptomic and metabolomic data demonstrated that MWWE
      exposure induced perturbations of metabolism, including lipid, nucleotide, amino
      acid, and energy metabolism. Furthermore, dysregulation of signal transduction
      processes were also identified based on differentially expressed genes. These
      results suggested that chronic exposure to MWWE could induce hepatotoxicity and
      nephrotoxicity in mice and omic approaches are of practical value to evaluate the
      complex toxicity of MWWE. 

PMID- 23883475
TI  - Rubabel: wrapping open Babel with Ruby.
AB  - BACKGROUND: The number and diversity of wrappers for chemoinformatic toolkits
      suggests the diverse needs of the chemoinformatic community. While existing
      chemoinformatics libraries provide a broad range of utilities, many
      chemoinformaticians find compiled language libraries intimidating, time
      consuming, arcane, and verbose. Although high-level language wrappers have been
      implemented, more can be done to leverage the intuitiveness of object
      orientation, the paradigms of high-level languages, and the extensibility of
      languages such as Ruby. We introduce Rubabel, an intuitive, object-oriented suite
      of functionality that substantially increases the accessibily of the tools in the
      Open Babel chemoinformatics library. RESULTS: Rubabel requires fewer lines of
      code than any other actively developed wrapper, providing better object
      organization and navigation, and more intuitive object behavior than extant
      solutions. Moreover, Rubabel provides a convenient interface to the many
      extensions currently available in Ruby, greatly streamlining otherwise onerous
      tasks such as creating web applications that serve up Rubabel functionality.
      CONCLUSIONS: Rubabel is powerful, intuitive, concise, freely available, cross
      platform, and easy to install. We expect it to be a platform of choice for new
      users, Ruby users, and some users of current solutions.

PMID- 23883476
TI  - European regulator appeals against order stopping it from releasing clinical
      study documents.

PMID- 23883478
TI  - The optimal use of cardiac imaging in the quantification of carcinoid heart
      disease.
AB  - Carcinoid heart disease is a rare cause of right-sided valvular dysfunction,
      primarily mediated by serotonin. It is an important complication in patients with
      carcinoid syndrome and occurs in 20-50% of such patients. Echocardiography is the
      main technique used for the assessment of carcinoid heart disease, but other
      imaging modalities are also important, particularly in the quantification of the
      severity of the disease. We sought to review the role of cardiac imaging in the
      assessment of carcinoid heart disease.

PMID- 23883477
TI  - Adventitial dissection: a simple and effective way to reduce radial artery spasm
      in coronary bypass surgery.
AB  - OBJECTIVES: Over the last two decades, the radial artery (RA) has become a
      routinely used conduit for coronary artery bypass graft surgery. One potential
      disadvantage of the radial artery is its higher susceptibility to vasospasm
      compared with other arterial grafts. We investigated whether adventitial
      dissection of the radial artery can reduce vasoconstriction and increase free
      blood flow. METHODS: Following harvesting, the adventitia of the radial artery
      was dissected using coronary scissors. Surplus distal radial artery segments (n =
      35) with and without adventitial dissection of patients undergoing coronary
      artery bypass surgery were collected and pairwise assessment of vasoreactivity to
      potassium chloride, U46619 and acetylcholine was performed in organ bath
      experiments. Free blood flow was measured before and after adventitial
      dissection. RESULTS: Full curve and maximal vasoconstriction of the RA to
      potassium chloride (P = 0.015 and 0.001) and U46619 (P = 0.048 and 0.001) was
      significantly reduced after adventitial dissection compared with non-adventitial
      dissected radial arteries. Endothelium-dependent relaxation to acetylcholine of
      adventitial dissected radial arteries was significantly increased (P = 0.006)
      compared with non-adventitial dissected radial arteries. Maximal vasorelaxation
      to acetylcholine was significantly increased for adventitial dissected radial
      arteries compared with non-adventitial dissected radial arteries (P = 0.018).
      Free blood flow was significantly increased after adventitial dissection (P =
      0.037). CONCLUSIONS: The adventitial dissected radial artery is less susceptible
      to vasoconstriction and more prone to vasorelaxation ex vivo and shows an
      increased free blood flow. Therefore, we suggest adventitial dissection of the
      radial artery graft to reduce vasospasm for arterial revascularization in
      coronary artery bypass surgery.

PMID- 23883479
TI  - Endoplasmic reticulum stress-mediated apoptosis in imatinib-resistant leukemic
      K562-r cells triggered by AMN107 combined with arsenic trioxide.
AB  - The first tyrosine kinase inhibitor (TKI) imatinib mesylate (imatinib) targets
      the kinase domain of BCR-ABL and induces apoptosis in newly diagnosed chronic
      myeloid leukaemia (CML). However, resistant and relapse are common problems in
      imatinib-treated patients. Although second-generation TKI such as AMN107 appears
      to improve the treatment of CML, TKI resistance and relapse are also frequently
      occurred in the patients. To test whether arsenic trioxide (ATO) could potentiate
      the efficacy of AMN107 in imatinib-resistant cells, we conducted a series of
      assays in TKI-resistant K562-r cells treated with AMN107 and ATO. Based on a time
      course cDNA microarray analysis, we found many genes typically involved in the
      endoplasmic reticulum (ER) stress signalling were significantly up-regulated,
      implicating the occurrence of ER stress-mediated apoptosis in K562-r cells
      treated with the combination of ATO and AMN107. Such implication was also
      supported by the data showing the activation of members in the JNK pathway, which
      are known to be characteristic markers bridging ER-stress and apoptosis. Partial
      knock-down of the JNK activities alleviated the effects of apoptosis (p < 0.05)
      triggered by combining AMN107 with ATO. In conclusion, this study for the first
      time demonstrates a synergistic effect of AMN107 with ATO, allowing insights into
      the possible mechanisms underlying imatinib-induced resistance in CML. Our data
      also suggest that combination of AMN107 with ATO may represent a new strategy for
      the treatment of imatinib-resistant CML patients. 

PMID- 23883480
TI  - Early acute pancreatitis in a child with compound heterozygosis
      ?F508/R1438W/Y1032C cystic fibrosis: a case report.
AB  - INTRODUCTION: Recent studies suggest an important role of the cystic fibrosis
      transmembrane conductance regulator gene in the development of pancreatitis. It
      occurs approximately in 20% of patients with cystic fibrosis and almost
      exclusively in pancreatic sufficient people. Newborn screening and improved
      panels of deoxyribonucleic acid mutation analysis techniques are revealing more
      rare and nonclassical pictures of the disease, generally associated with
      pancreatic sufficiency and with an increased risk of developing pancreatitis.
      Mutations R1438 and Y1032 are considered rare mutations, and, when singularly
      associated with ?F508, lead to a mild phenotype with pancreatic sufficiency and
      no detectable respiratory involvement. CASE PRESENTATION: We present the case of
      a Caucasian girl, aged six years, whose genotype was characterized by three
      different mutations ?F508, R1438W and Y1032C, never reported, together, in the
      same patient. She presented with a positive immunoreactive trypsinogen screening,
      a borderline sweat test, and, in the first years, a favorable pulmonary course,
      and pancreatic sufficiency. At the age of six years, she presented with a sudden
      episode of acute abdominal pain, anorexia and fever. A diagnosis of pancreatitis
      was made after clinical and laboratory examinations. Venous rehydration, bowel
      rest and therapy with ursodeoxycholic acid resulted in complete remission.The
      treatment was successful, with normalization of her symptoms and laboratory
      parameters within four weeks. CONCLUSION: There has been a vast expansion in the
      understanding of the wide range of phenotypes associated with cystic fibrosis
      transmembrane conductance regulator dysfunction since the discovery of the cystic
      fibrosis transmembrane conductance regulator gene. The genotype-phenotype
      correlation in pancreatitis is rare compared to other organ manifestations, since
      this is seen almost exclusively among pancreatic sufficient patients with cystic
      fibrosis. Our study supports that compound heterozygosis ?F508-R1438W/Y1032C is a
      'cystic fibrosis-causing genotype' characterized by an immunoreactive trypsinogen
      positive screening, abnormal sweat chloride testing, and pancreatic sufficiency,
      with an increased risk of acute pancreatitis at an early age.

PMID- 23883482
TI  - A prototype portable breath acetone analyzer for monitoring fat loss.
AB  - Acetone contained in our exhaled breath is a metabolic product of the breakdown
      of body fat and is expected to be a good indicator of fat-burning. Typically, gas
      chromatography or mass spectrometry are used to measure low-concentration
      compounds in breath but such large instruments are not suitable for daily use by
      diet-conscious people. Here, we prototype a portable breath acetone analyzer that
      has two types of semiconductor-based gas sensors with different sensitivity
      characteristics, enabling the acetone concentration to be calculated while taking
      into account the presence of ethanol, hydrogen, and humidity. To investigate the
      accuracy of our prototype and its application in diet support, experiments were
      conducted on healthy adult volunteers. Breath acetone concentrations obtained
      from our prototype and from gas chromatography showed a strong correlation
      throughout the experiments. Moreover, body fat in subjects with a controlled
      caloric intake and taking exercise decreased significantly, whereas breath
      acetone concentrations in those subjects increased significantly. These results
      prove that our prototype is practical and useful for self-monitoring of fat
      burning at home or outside. Our prototype will help to prevent and alleviate
      obesity and diabetes. 

PMID- 23883481
TI  - Effects of a new pocket device for negative pressure wound therapy on surgical
      wounds of patients affected with Crohn's disease: a pilot trial.
AB  - INTRODUCTION: Surgical site infections (SSIs) affect costs of care and prolong
      length of stay. Crohn's disease (CD) represents an independent risk factor for
      SSI. The risk can be further increased by concomitant administration of
      immunosuppressive drugs and poor performance status at the time of surgery.
      Patients suffering from CD often need more than one surgical intervention during
      life, sometimes requiring fashioning of a stoma. The aim of this pilot study was
      to compare a portable device for negative pressure wound therapy (PICO, Smith &
      Nephew, London, UK) to conventional gauze dressings in patients undergoing
      surgery for stricturing CD. METHODS: Between January 2010 and November 2011, this
      controlled trial enrolled 30 patients, who were assigned to treatment with either
      PICO (n = 13) or conventional dressings (n = 17). Each patient completed a 3
      month follow-up. RESULTS: Patients receiving PICO experienced significantly less
      postoperative wound complications (P = .001) and SSI (P = .017) compared with
      those who received conventional dressings. This resulted in shorter hospital stay
      (P = .0007). No significant differences in cosmetic results were found.
      CONCLUSION: These data suggest that PICO allows faster and safe discharge by
      reducing the incidence of SSI and wound-related complications in selected
      patients undergoing surgical intervention for stricturing CD. This could be
      particularly useful in patients receiving steroids.

PMID- 23883483
TI  - Transport properties in a Sb-Te binary topological-insulator system.
AB  - Sb-Te layers having various compositions between Sb2Te3 and Sb2Te are grown using
      molecular beam epitaxy. The structural and electrical properties of the layers
      change gradually with composition but exhibit a discontinuity involving a
      bistability. The holes in the layers are generated by Sb bilayers intercalated
      between Sb2Te3 quintuple layers and their mobility is governed by the scattering
      from the parent acceptors. Magnetoresistance for compositions around SbTe is
      linear, for which the reduction of the parabolic component due to low mobility is
      crucial. Density functional calculations predict Sb2Te3 and SbTe to be
      topological insulators (TIs) resembling Bi2Se3 and Bi2Te3, respectively. The
      prefactor of the weak antilocalization effect is alpha =- 1 regardless of the
      composition. The Sb-Te system is thus a family of TIs possessing undisturbed
      surface states for which the location of the Dirac point with respect to the bulk
      band gap is adjustable. 

PMID- 23883484
TI  - Anterior uveitis secondary to type II essential cryoglobulinemia.
AB  - BACKGROUND: The purpose of this report is to describe the association of severe
      anterior uveitis with type II essential cryoglobulinemia. FINDINGS: A 40-year-old
      male with a history of psoriatic arthritis presented with severe anterior uveitis
      associated with type II essential cryoglobulinemia. His uveitis, refractory to
      steroid treatments, was well controlled following treatments for
      cryoglobulinemia. The temporal association between his cryoglobulinemia and
      uveitis, combined with his improved visual acuity and inflammation after
      plasmapheresis and rituximab infusions, suggests cryoglobulinemia to be the
      underlying condition of his uveitis. CONCLUSIONS: To our best knowledge, this is
      the first reported case of anterior uveitis secondary to type II essential
      cryoglobulinemia.

PMID- 23883485
TI  - Kampo formulations, chotosan, and yokukansan, for dementia therapy: existing
      clinical and preclinical evidence.
AB  - Cognitive deficits and behavioral and psychological symptoms of dementia (BPSD)
      are typical features of patients with dementia such as Alzheimer's disease (AD),
      vascular dementia (VD), and other forms of senile dementia. Clinical evidence has
      demonstrated the potential usefulness of chotosan (CTS) and yokukansan (YKS),
      traditional herbal formulations called Kampo medicines, in the treatment of
      cognitive disturbance and BPSD in dementia patients, although the indications
      targeted by CTS and YKS in Kampo medicine differ. The availability of CTS and YKS
      for treating dementia patients is supported by preclinical studies using animal
      models of dementia that include cognitive/emotional deficits caused by aging and
      diabetes, dementia risk factors. These studies have led not only to the concept
      of a neuronal basis for the CTS- and YKS-induced amelioration of cognitive
      function and emotional/psychiatric symptom-related behavior in animal models, but
      also to a proposal that ingredient(s) of Uncariae Uncis cum Ramulus, a medicinal
      herb included in CTS and YKS, may play an important role in the actions of these
      formulae in dementia patients. Further studies are needed to clarify the active
      ingredients of these formulae and their target endogenous molecules implicated in
      the anti-dementia drug-like actions. 

PMID- 23883486
TI  - Negative correlation between Per1 and Sox6 expression during chondrogenic
      differentiation in pre-chondrocytic ATDC5 cells.
AB  - Pre-chondrocytes undergo cellular differentiation stages during chondrogenesis
      under the influence by different transcription factors such as sry-type high
      mobility group box-9 (Sox9) and runt-related transcription factor-2 (Runx2). We
      have shown upregulation by parathyroid hormone (PTH) of the clock gene Period-1
      (Per1) through the cAMP/protein kinase A signaling pathway in pre-chondrocytic
      ATDC5 cells. Here, we investigated the role of Per1 in the suppression of
      chondrogenic differentiation by PTH. In ATDC5 cells exposed to 10 nM PTH, a
      drastic but transient increase in Per1 expression was seen only 1 h after
      addition together with a prolonged decrease in Sox6 levels. However, no
      significant changes were induced in Sox5 and Runx2 levels in cells exposed to
      PTH. In stable Per1 transfectants, a significant decrease in Sox6 levels was
      seen, with no significant changes in Sox5 and Sox9 levels, in addition to the
      inhibition of gene transactivation by Sox9 allies. Knockdown of Per1 by siRNA
      significantly increased the Sox6 and type II collagen levels in cells cultured
      for 24 - 60 h. These results suggest that Per1 plays a role in the suppressed
      chondrocytic differentiation by PTH through a mechanism relevant to negative
      regulation of transactivation of the Sox6 gene during chondrogenesis. 

PMID- 23883487
TI  - Conventional concepts and new perspectives for understanding the addictive
      properties of inhalants.
AB  - The abuse of inhaled chemical vapors is a growing problem especially among
      adolescent populations. This is partly driven by the fact that inhaled products
      are cheap, accessible, and provide a rapid 'high'. In the brain inhalants have
      multiple effects. They are neurotoxic, targeting primarily white matter pathways,
      which is believed to underlie the long-term neurological consequences associated
      with repeated use. Inhalants are also addictive, resulting in adaptive responses
      in pathways mediating reward and reinforcement. This includes an ability to alter
      dopaminergic cell firing and result in long-term mesocorticolimbic dopaminergic
      dysfunction. However, growing evidence suggests that the reinforcing properties
      of inhalants may also be driven by their ability to affect neurotransmitter
      systems other than the dopaminergic system. Both glutamatergic and g-aminobutyric
      acid (GABA)ergic systems are emerging as key targets of inhalants with
      differential responses observed following either acute or chronic exposures.
      These responses appear particularly important in circuits which appear vulnerable
      to inhalants and which can also modulate dopaminergic function such as the
      corticostriatal pathway. Thus in combination with the effects of inhalants on
      dopaminergic systems, our increased understanding of the role(s) of glutamatergic
      and GABAergic systems provide new and exciting targets to consider for
      intervention strategies to limit inhalant use. 

PMID- 23883488
TI  - Increased plasma levels of heparin-binding protein in patients with acute
      respiratory distress syndrome.
AB  - INTRODUCTION: Heparin-binding protein (HBP) is an antimicrobial protein stored in
      neutrophil granules and plays a role in endothelial permeability regulation. The
      aim was to assess the diagnostic and prognostic value of measuring HBP in
      patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS).
      METHODS: Plasma HBP was collected from 78 patients with ALI/ARDS, 28 patients
      with cardiogenic pulmonary edema (CPE) and 20 healthy volunteers at enrollment.
      Levels of HBP were measured by ELISA. RESULTS: Patients with ALI/ARDS had
      significantly higher median levels of HBP compared with patients with CPE (17.15
      (11.95 to 24.07) ng/ml vs. 9.50 (7.98 to 12.18) ng/ml, P <0.001) at enrollment.
      There was no significant difference between CPE patients and healthy subjects in
      terms of HBP value (P = 0.372). The HBP levels of nonsurvivors was significantly
      higher than that of survivors (23.90 (14.81 to 32.45) ng/ml vs. 16.01 (10.97 to
      21.06) ng/ml, P = 0.012) and multivariate logistic regression showed HBP (odds
      ratio =1.52, P = 0.034) was the independent predictor for 30-day mortality in
      patients with ALI/ARDS. CONCLUSIONS: Plasma HBP levels of ALI/ARDS patients were
      significantly higher than that of CPE patients. HBP was a strong prognostic
      marker for short-term mortality in ALI/ARDS.

PMID- 23883489
TI  - Dyadic interventions for community-dwelling people with dementia and their family
      caregivers: a systematic review.
AB  - BACKGROUND: In this review, we study the effects of dyadic psychosocial
      interventions focused on community-dwelling people with dementia and their family
      caregivers, and the relationship of the effects with intervention components of
      programs. METHODS: A search from January 2005 to January 2012 led to 613 hits,
      which we reviewed against our inclusion criteria. We added studies from 1992 to
      2005 reviewed by Smits et al. (Smits, C. H. M., De Lange, J., Droes, R.-M.,
      Meiland, F., Vernooij-Dassen, M. and Pot, A. M. (2007). Effects of combined
      intervention programs for people with dementia living at home and their
      caregivers: a systematic review. International Journal of Geriatric Psychiatry,
      22, 1181-1193). We assessed the methodological quality of 41 programs with the
      Cochrane criteria and two items of the Oxford Centre of Evidence-based Medicine
      guidelines. RESULTS: Studies of moderate to high quality concerning 20 different
      dyadic psychosocial programs for people with dementia and caregivers were
      included. Nineteen of these programs show significant effects on the patient with
      dementia, the caregiver, or both. Due to differences in the programs and the
      studies, this study does not provide an unequivocal answer about which programs
      are most effective. Programs with intervention components that actively train one
      or more specific functional domains for the person with dementia and/or the
      caregiver seem to have a beneficial impact on that domain, although there are
      exceptions. Reasons can be found in the program itself, the implementation of the
      program, and the study design. CONCLUSIONS: Dyadic psychosocial programs are
      effective, but the outcomes for the person with dementia and the caregiver vary.
      More attention is needed for matching the targeted functional domains,
      intervention components, and delivery characteristics of a program with the needs
      of the person with dementia and the family caregiver.

PMID- 23883490
TI  - Identification and use of operating room efficiency indicators: the problem of
      definition.

PMID- 23883491
TI  - Preoperative factors predicting poor outcomes following laparoscopic
      choledochotomy: a multivariate analysis study.
AB  - BACKGROUND: Laparoscopic surgery for common bile duct stones varies procedurally
      from a transcystic approach to laparoscopic choledochotomy (LC) with or without
      biliary drainage. However, LC is a difficult procedure with higher documented
      morbidity than the transcystic approach. We retrospectively investigated risk
      factors for adverse outcomes of LC. METHODS: We used logistic regression models
      to assess 4 categories of adverse outcomes: overall, complications, conversion to
      open operation and failed surgical clearance. We calculated the area under the
      receiver operating characteristic curve to evaluate diagnostic accuracy. RESULTS:
      We included 201 patients who underwent LC in our analysis. Adverse outcomes
      occurred in 48 (23.9%) patients, complications occurred in 43 (21.4%), retained
      stones were observed in 8 (4%), and conversion to laparotomy occurred in 7
      (3.5%). Multivariate analysis showed that total bilirubin (BIL) and the presence
      of medical risk factors (MRFs) were significant predictors of adverse outcomes
      and complications. We calculated the probability of adverse outcomes (p) using
      the following formula: logit(p) = 0.977 (MRFs) + 0.014 (BIL) - 2.919. p = EXP
      (logit(p)) / [1+EXP (logit(p))]. According to their logit(p), all patients were
      divided into a low-risk group (logit(p) <= -1.32, n = 130) and a high-risk group
      (logit(p) > -1.32, n = 71). Patients in the low-risk group had about a 1 in 10
      chance (12 of 130) of adverse outcomes developing. Of the 71 patients in the high
      risk group, 36 (50.7%) experienced adverse outcomes. CONCLUSION: High BIL and the
      presence of MRFs could predict adverse outcomes in patients undergoing LC.

PMID- 23883492
TI  - Outcomes of the adjustable gastric band in a publicly funded obesity program.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is considered a safe
      and effective treatment for severe obesity and obesity-related comorbidities. We
      sought to examine the outcome of LAGB delivered through a Canadian publicly
      funded obesity program. METHODS: We retrospectively analysed the cases of
      patients who underwent LAGB within a comprehensive, multidisciplinary, publically
      funded obesity program. RESULTS: A total of 178 patients underwent LAGB. Mean
      percentage total body weight loss at 1, 2 and 3 years was 15.8%, 20.7% and 20.3%,
      respectively. The most common short-term complication was postoperative nausea
      (19%). The medium-term complications included band migration (5.6%) and port site
      complications, band leakage and incisional hernia at 1% each. The reoperation
      rate was 4.5%. The mean surgery duration was 56 minutes and the mean length of
      stay was 1.4 days. The average numbers of clinic visits and band adjustments were
      highest in the first year. The most common investigation for postoperative
      symptoms was fluoroscopy (86%). An outcome comparison between the 2 generations
      of the REALIZE gastric band was inconclusive, requiring further data collection.
      CONCLUSION: Publicly funded LAGB results in effective weight loss and acceptable
      safety over the short term. Our patients may represent a distinct population that
      differs from that in the private system. Long-term data are necessary to
      determine the cost-effectiveness of this important surgical option for severe
      obesity.

PMID- 23883493
TI  - Physicians' awareness of cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy for colorectal cancer carcinomatosis.
AB  - BACKGROUND: Recent trials have shown that cytoreductive surgery and heated
      intraperitoneal chemotherapy (S+HIPEC) for colorectal cancer carcinomatosis (CRC
      C) leads to 5-year, disease-free survival rates of more than 30%. Since these
      data represent a substantial change in the management of CRC-C, the objectives of
      this study were to determine physicians' awareness of S+HIPEC for CRC-C and
      physician characteristics predictive of awareness of S+HIPEC for CRC-C. METHODS:
      This study was a mailed, cross-sectional survey of general surgeons and medical
      oncologists in Ontario. RESULTS: The response rate was 44.0% (214 of 487). Most
      respondents were men and younger than 50 years. There was an even split between
      those at academic and community hospitals. Overall, 46% of respondents were aware
      of S+HIPEC for CRC-C, and multivariate analysis showed that there were no
      physician characteristics predictive of awareness of S+HIPEC for CRC-C.
      CONCLUSION: Physician awareness of S+HIPEC for CRC-C is low. Therefore,
      strategies to improve patient and physician knowledge about S+HIPEC for CRC-C are
      important to ensure appropriate treatment for patients.

PMID- 23883494
TI  - Transanal endoscopic microsurgery: impact on fecal incontinence and quality of
      life.
AB  - BACKGROUND: Anal dilation during tumour excision with transanal endoscopic
      microsurgery (TEM) has caused concerns regarding postoperative anal function. We
      sought to determine whether TEM affects anorectal function and quality of life.
      METHODS: All patients undergoing TEM between March 2007 and December 2008 were
      considered for inclusion. We excluded patients who were treated with subsequent
      radical resection, unavailable for interview or deceased. Patients were
      interviewed by phone to measure the preoperative and postoperative function using
      the European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire- Core 30 (EORTC QLQ-C30) and Core 38 (CR38) instruments, the Fecal
      Incontinence Severity Index (FISI) and the Fecal Incontinence Quality of Life
      (FIQL) questionnaires. Statistical analysis involved the Wilcoxon signed rank
      test and Spearman rank correlation coefficient. RESULTS: Forty patients received
      TEM; 30 of them met all inclusion criteria and agreed to participate. The median
      age was 70 (42-93) years, and median follow-up time between the interview and the
      operation was 365 (55-712) days. Tumours excised included 19 adenomas, 8
      carcinomas and 3 carcinoid tumours. The median distance from the tumour to the
      anal verge was 6.5 (2-13) cm. Median length of stay was 1 (0-12) day. For most
      aspects of quality of life, there were no detectable differences after surgery.
      The EORTC QLQ-C30 showed a significant improvement in diarrhea (27.8 v. 10, p =
      0.002). The FIQL scores improved with surgery (3.59 v. 3.85, p = 0.020). There
      was no difference in pre- versus postoperative FISI scores (6.7 v. 6.3, p =
      0.93). CONCLUSION: Despite a large operating rectoscope, TEM improves quality of
      life related to fecal incontinence and does not have a negative impact on fecal
      continence.

PMID- 23883495
TI  - Oncologic specimen from laparoscopic assisted gastrectomy for gastric
      adenocarcinoma is comparable to D1-open surgery: the experience of a Canadian
      centre.
AB  - BACKGROUND: The Eastern experience has reported the safety of laparoscopic
      assisted gastrectomy (LAG) for gastric cancer. Its use in Western countries is
      still debated owing to concerns about its oncologic equivalence to open
      gastrectomy (OG). We sought to review and compare their operative outcomes and
      oncologic specimen quality (number of harvested lymph nodes and surgical margins)
      for gastric adenocarcinoma (GA). METHODS: We reviewed the charts of all patients
      undergoing LAG (2007-2010) and OG (2000-2010) for GA in a single institution.
      Several surgeons performed the OGs, whereas 1 fellowship-trained laparoscopic
      surgeon performed LAGs. The primary outcome was quality of the surgical specimen,
      assessed by the number of harvested lymph nodes (LNs) and margin status.
      Secondary outcomes were perioperative events. Data were analyzed as intention to
      treat. RESULTS: We retrieved 60 cases (47 OGs, 13 LAGs). The conversion rate was
      23%. Mean operative time was 115 minutes longer and blood loss was 425 mL less
      (both p < 0.001) for LAGs. A mean of 14.4 (standard deviation [SD] 9.8) and 11.2
      (SD 8.2) LNs were harvested for OGs and LAGs, respectively (p = 0.29). Negative
      margins were achieved for all patients. Mean length of stay was similar (LAG: 19
      d v. OG: 18.9 d; p = 0.91). The groups did not differ on major postoperative
      complications (12.7% v. 23.1%; p = 0.39) or operative mortality (2.1% v. 7.7%; p
      = 0.32). CONCLUSION: Laparoscopic assisted gastrectomy is a challenging but safe
      and feasible procedure in experienced hands. It offers the same radical resection
      as OG regarding negative margins and LN retrieval. Long-term follow-up is
      warranted.

PMID- 23883496
TI  - Survival after hepatic resection: impact of surgeon training on long-term
      outcome.
AB  - BACKGROUND: Mortality for liver resection has remarkably improved owing to
      multiple factors. We sought to determine the impact of the various types of
      fellowship training on patient survival after liver resection. METHODS: Patients
      who underwent hepatic resection between 1995 and 2004 in either the Calgary or
      Capital health regions (Edmonton) of Alberta, Canada, were identified using ICD-9
      and -10 codes. Primary outcomes included in-hospital mortality and patient
      survival according to surgeon volume and training type (surgical oncology v.
      hepatobiliary v. others). RESULTS: A total of 1033 patients underwent hepatic
      resection. Surgeon volume was not predictive of either in-hospital mortality
      (adjusted odds ratio 0.63, 95% confidence interval [CI] 0.32-1.20) or patient
      survival (unadjusted hazard ratio 1.11, 95% CI 0.82-1.51). Nonsignificance was
      also demonstrated for a surgeon's type of fellowship training. CONCLUSION: The
      various modes of fellowship training do not appear to influence inhospital
      mortality or patient survival after hepatic resection.

PMID- 23883497
TI  - Use of safety scalpels and other safety practices to reduce sharps injury in the
      operating room: what is the evidence?
AB  - BACKGROUND: The occupational hazard associated with percutaneous injury in the
      operating room (OR) has encouraged harm reduction through behaviour change and
      the use of safety-engineered surgical sharps. Some Canadian regulatory agencies
      have mandated the use of "safety scalpels." Our primary objective was to
      determine whether safety scalpels reduce the risk of percutaneous injury in the
      OR, while a secondary objective was to evaluate risk reduction associated with
      other safety practices. METHODS: We used evidence review methods described by the
      International Liaison Committee on Resuscitation and conducted a systematic,
      English-language search of Ovid, MEDLINE and EMBASE using the following search
      terms: "safety-engineered scalpel," "mistake proofing device,"
      "retractable/removable blade/scalpel," "pass tray," "hands free passing,"
      "neutral zone," "sharpless surgery," "double/cutproof gloving" and "blunt suture
      needles." Included articles were scored according to level of evidence; quality;
      and whether they were supportive, opposed or neutral to the study question(s).
      RESULTS: Of 72 included citations, none was supportive of the use of safety
      scalpels. There was high-level/quality evidence (Cochrane reviews) in support of
      risk reduction through double-gloving and use of blunt suture needles, with
      additional evidence supporting a pass tray/neutral zone for sharps handling (4 of
      5 articles supportive) and use of suturing adjuncts (1 article supportive).
      CONCLUSION: There is insufficient evidence to support regulated use of safety
      scalpels. Injury-reduction strategies should emphasize proven methods, including
      double-gloving, blunt suture needles and use of hands-free sharps transfer.

PMID- 23883498
TI  - The lateral radiograph is useful in predicting shortening in 31A2 pertrochanteric
      hip fractures.
AB  - BACKGROUND: We sought to determine if angulation or translation measured on the
      lateral preoperative injury radiographs of patients with 31A2 pertrochanteric
      fractures is related to excessive postoperative shortening when treated with a
      sliding hip screw. METHODS: We retrospectively reviewed the radiographs of
      consecutive patients with hip fractures treated at a level I university trauma
      centre between 2003 and 2008. Patients with 31A2 pertrochanteric fractures
      treated with a sliding hip screw were identified through a search of medical
      records. The study variables were angulation and translation on the preoperative
      injury lateral radiograph. The outcome measure was radiographic evidence of
      fracture shortening, measured as the change in length of sliding hip screw
      visible outside the barrel between the time of fixation and final follow up.
      RESULTS: Of the 131 patients treated, 23 met our inclusion criteria and had
      sufficient follow-up (mean 6.4 mo). The average shortening for 31A2 fractures
      with angulation on the injury lateral radiograph was 1.83 (95% confidence
      interval [CI] 1.18-2.47) cm, compared with 0.93 (95% CI 0.49-1.36) cm for
      fractures with no angulation (p = 0.019). There was no statistical difference in
      quality of reduction, tip-apex distance, Orthopedic Trauma Association (AO/OTA)
      classification or incidence of lateral wall fracture across groups based on the
      presence of angulation. CONCLUSION: Angulation on the lateral preoperative injury
      radiograph may be useful in predicting excessive shortening in 31A2
      pertrochanteric fractures. Further investigation is warranted to confirm this
      result and to identify the role of other predictors, such as fracture
      comminution.

PMID- 23883499
TI  - Medicine versus surgery/anesthesiology intensivists: a retrospective review and
      comparison of outcomes in a mixed medical-surgical-trauma ICU.
AB  - BACKGROUND: With various types of complex patients being treated in a mixed
      medical- surgical- trauma intensive care unit (ICU), we hypothesized that there
      should be no difference in patient mortality with respect to the core training of
      the intensivist. METHODS: We reviewed the cases of all patients admitted to a
      mixed medical-surgical-trauma ICU at a Canadian university teaching hospital in
      2007. Patients were assigned to 1 of 2 treatment groups (internal medicine,
      surgery/anesthesiology) based on the treating intensivist's training. Our primary
      outcome was to compare patient mortality in the ICU between the groups. We used
      generalized estimating equations to determine 10-day mortality after admission to
      the ICU. A multivariate Cox hazard model was used to determine statistical
      significance and 95% confidence intervals (CIs) for 11- to 60-day mortality in
      the ICU. RESULTS: A total of 961 patients were admitted from January to December,
      2007. We found no significant difference between the groups in 10-day mortality
      (odds ratio 0.73, 95% CI 0.46-1.18, p = 0.20) and 11- to 60-day mortality (hazard
      ratio 1.43, 95% CI 0.62-3.30, p = 0.40) after admission to the ICU. CONCLUSION:
      In a large university trauma centre that operates a mixed medicine- surgical
      trauma ICU, there was no significant difference in mortality between patients
      managed by intensivists with core training in internal medicine and those managed
      by intensivists with training in surgery/anesthesiology.

PMID- 23883500
TI  - Minimally invasive splenectomy: an update and review.
AB  - Laparoscopic splenectomy (LS) has become an established standard of care in the
      management of surgical diseases of the spleen. The present article is an update
      and review of current procedures and controversies regarding minimally invasive
      splenectomy. We review the indications and contraindications for LS as well as
      preoperative considerations. An individual assessment of the procedures and
      outcomes of multiport laparoscopic splenectomy, hand-assisted laparoscopic
      splenectomy, robotic splenectomy, natural orifice transluminal endoscopic
      splenectomy and single-port splenectomy is included. Furthermore, this review
      examines postoperative considerations after LS, including the postoperative
      course of uncomplicated patients, postoperative portal vein thrombosis,
      infections and malignancy. 

PMID- 23883501
TI  - Canadian contribution to the ACS.

PMID- 23883503
TI  - Surgery on a global scale at Western University.

PMID- 23883504
TI  - Retrospective review of rectal cancer surgery in northern Alberta.
AB  - INTRODUCTION: Previous studies, including research published more than 10 years
      ago in Northern Alberta, have demonstrated improved outcomes with increased
      surgical volume and subspecialisation in the treatment of rectal cancer. We
      sought to examine contemporary rectal cancer care in the same region to determine
      whether practice patterns have changed and whether outcomes have improved.
      METHODS: We reviewed the charts of all patients with rectal adenocarcinoma
      diagnosed between 1998 and 2003 who had a potentially curative resection. The
      main outcomes examined were 5-year local recurrence (LR) and disease-specific
      survival (DSS). Surgeons were classified into 3 groups according to training and
      volume, and we compared outcome measures among them. We also compared our results
      to those of the previous study from our region. RESULTS: We included 433 cases in
      the study. Subspecialty-trained colorectal surgeons performed 35% of all
      surgeries in our study compared to 16% in the previous study. The overall 5-year
      LR rate and DSS in our study were improved compared to the previous study. On
      multivariate analysis, the only factor associated with increased 5-year LR was
      presence of obstruction, and the factors associated with decreased 5-year DSS
      were high-volume noncolorectal surgeons, presence of obstruction and increased
      stage. CONCLUSION: Over the past 10 years, the long-term outcomes of treatment
      for rectal cancer have improved. We found that surgical subspecialization was
      associated with improved DSS but not LR. Increased surgical volume was not
      associated with LR or DSS.

PMID- 23883505
TI  - Celebrity traumatic deaths: are gangster rappers really "gangsta"?
AB  - BACKGROUND: Celebrity injury-related deaths are a common topic of conversation
      and receive wide media coverage. Despite stereotypes and broad generalizations,
      it is unclear if the mechanisms of demise echo those of the general population.
      The objective of this study was to evaluate the epidemiology underlying celebrity
      traumatic deaths. METHODS: We evaluated all known injury-related deaths in
      celebrities (musicians, athletes, actors, politicians and celebrity socialites)
      that occurred between Jan. 1, 2000, and Sept. 1, 2011. Exclusion criteria were
      drug/alcohol overdoses and suicides. We used standard statistical methodology.
      RESULTS: Among 389 celebrities who died because of their injuries, motor vehicle
      collisions remained the most common mechanism overall. Rappers and politicians
      had a higher proportion of deaths due to interpersonal violence than all other
      celebrities. Gunshot wounds were most common in these cohorts (83% and 63%,
      respectively). Rappers and athletes also died at a younger mean age than other
      celebrities. Sport-related deaths were most common in boxing and mixed martial
      arts. Additional mechanisms included airplane crashes, animal interactions and
      recreational activities. CONCLUSION: Despite occasionally exotic scenarios, most
      celebrities die of injury mechanisms similar to those of the general population.
      It is also apparent that rappers and politicians die by violent means at young
      and middle ages, respectively, more commonly than all other celebrities.

PMID- 23883506
TI  - Interest and applicability of acute care surgery among surgeons in Quebec: a
      provincial survey.
AB  - BACKGROUND: Acute care surgery (ACS) comprises trauma and emergency surgery. The
      purpose of this new specialty is to involve trauma and nontrauma surgeons in the
      care of acutely ill patients with a surgical pathology. In Quebec, few acute care
      surgery services (ACSS) exist, and the concept is still poorly understood by most
      general surgeons. This survey was meant to determine the opinions and interest of
      Quebec general surgeons in this new model. METHODS: We created a bilingual
      electronic survey using a Web interface and sent it by email to all surgeons
      registered with the Association quebecoise de chirurgie. A reminder was sent 2
      weeks later to boost response rates. RESULTS: The response rate was 36.9%. Most
      respondents had academic practices, and 16% worked in level 1 trauma centres.
      Most respondents had a high operative case load, and 66% performed at least 10
      urgent general surgical cases per month. Although most (88%) thought that ACS was
      an interesting field, only 45% were interested in participating in an ACSS.
      Respondents who deemed this concept least applicable to their practices were more
      likely to be working in nonacademic centres. CONCLUSION: Despite a strong
      interest in emergency general surgery, few surgeons were interested in
      participating in an ACSS. This finding may be explained by lack of comprehension
      of this new model and by comfort with traditional practice. We aim to change this
      paradigm by demonstrating the feasibility and benefits of the new ACSS at our
      centre in a follow-up study.

PMID- 23883507
TI  - Laparoscopic bariatric surgery can be performed safely in secondary health care
      centres with a dedicated service corridor to an affiliated tertiary health care
      centre.
AB  - BACKGROUND: Canada needs to increase capacity for bariatric surgery to reduce the
      wait for this cost-effective, life-saving surgery. The aim of this study was to
      test whether laparoscopic bariatric surgery, including gastric bypass, can be
      delivered safely in secondary health care centres (SHCCs). METHODS: In this
      prospective cohort study, patients received bariatric surgery at an SHCC that had
      no intensive care unit but had a dedicated operating room and ward teams and a
      patient-monitoring environment. Patients with life-threatening complications were
      transferred to an affiliated tertiary health care centre (THCC) via a dedicated
      "service corridor." RESULTS: In all, 830 patients were treated: 676 at the SHCC
      and 154 at the THCC. Gastric bypass was performed in 85.4%, gastric band in 11.1%
      and gastric sleeve in 3.5%. The body mass index (BMI) was significantly higher in
      the THCC than the SHCC group (mean 54.4 [standard deviation (SD) 9.7] v. 47.5 [SD
      7.4]). Obesity-associated diseases were similar between the groups. Major
      complications occurred in 2.6% of SHCC patients and 1.7% of THCC patients. Seven
      patients (1%) required direct transfer to the THCC, and all were treated
      successfully. There were 2 deaths (1.3%) in the THCC and none in the SHCC groups
      (combined mortality 0.2%). Weight loss was equivalent up to the fourth year of
      the study. CONCLUSION: With proper patient selection, a dedicated health care
      team and a service corridor to an affiliated THCC, laparoscopic bariatric
      surgery, including gastric bypass can be performed safely in SHCCs. Further study
      is needed to determine whether the model can be applied across Canada.

PMID- 23883508
TI  - A look at the thoracic surgery workforce in Canada: how demographics and scope of
      practice may impact future workforce needs.
AB  - BACKGROUND: The purpose of this study is to describe the demographics, training
      and practice characteristics of physicians performing thoracic surgery across
      Canada to better assess workforce needs. METHODS: We developed a questionnaire
      using a modified Delphi process to generate questionnaire items. The
      questionnaire was administered to all Canadian thoracic surgeons via email (n =
      102) or mail (n = 35). RESULTS: In all, 97 surgeons completed the survey (71%
      response rate). The mean age of respondents was 47.7 (standard deviation 9.1)
      years; 10.3% were older than 60. Ninety respondents (88.7%) were men, 95 (81.1%)
      practised in English and 93 (76%) were born in Canada. Most (90.4%) had a medical
      school affiliation, with an equal proportion practising in community or
      university teaching hospitals. Only 18% of respondents reported working fewer
      than 60 hours per week, and 34% were on call more than 1 in 3. Three-quarters of
      work hours were devoted to clinical care, with the remaining time split among
      research, administration and teaching. Malignant lung disease accounted for 61.2%
      of practice time, with the remaining time equally split between benign and
      malignant thoracic diseases. Preoperative testing (49.4%) and insufficient
      operating time (49.5%) were the most common factors delaying delivery of care.
      More than 80% of respondents reported being satisfied with their careers, with
      62.1% planning on retiring after age 60. CONCLUSION: This survey characterizes
      Canadian thoracic surgeons by providing specific demographic, satisfaction and
      scope of practice information. Despite challenges in obtaining adequate resources
      for providing timely care, job satisfaction remains high, with a balanced
      workforce supply and demand anticipated for the foreseeable future.

PMID- 23883509
TI  - High-concentration oxygen and surgical site infections in abdominal surgery: a
      meta-analysis.
AB  - BACKGROUND: There has been recent interest in using high-concentration oxygen to
      prevent surgical site infections (SSIs). Previous meta-analyses in this area have
      produced conflicting results. With the publication of 2 new randomized controlled
      trials (RCTs) that were not included in previous meta-analyses, an updated review
      is warranted. Our objective was to perform a meta-analysis on RCTs comparing high
      and low- concentration oxygen in adults undergoing open abdominal surgery.
      METHODS: We completed independent literature reviews using electronic databases,
      bibliographies and other sources of grey literature to identify relevant studies.
      We assessed the overall quality of evidence using grade guidelines. Statistical
      analysis was performed on pooled data from included studies. A priori subgroup
      analyses were planned to explain statistical and clinical heterogeneity. RESULTS:
      Overall, 6 studies involving a total of 2585 patients met the inclusion criteria.
      There was no evidence of a reduction in SSIs with high-concentration oxygen (risk
      ratio 0.77, 95% confidence interval 0.50-1.19, p = 0.24). We observed substantial
      heterogeneity among studies. CONCLUSION: There is moderate evidence that high
      concentration oxygen does not reduce SSIs in adults undergoing open abdominal
      surgery.

PMID- 23883510
TI  - Feasibility and fidelity of practising surgical fixation on a virtual ulna bone.
AB  - BACKGROUND: Surgical simulators provide a safe environment to learn and practise
      psychomotor skills. A goal for these simulators is to achieve high levels of
      fidelity. The purpose of this study was to develop a reliable surgical simulator
      fidelity questionnaire and to assess whether a newly developed virtual haptic
      simulator for fixation of an ulna has comparable levels of fidelity as Sawbones.
      METHODS: Simulator fidelity questionnaires were developed. We performed a
      stratified randomized study with surgical trainees. They performed fixation of
      the ulna using a virtual simulator and Sawbones. They completed the fidelity
      questionnaires after each procedure. RESULTS: Twenty-two trainees participated in
      the study. The reliability of the fidelity questionnaire for each separate domain
      (environment, equipment, psychological) was Cronbach alpha greater than 0.70,
      except for virtual environment. The Sawbones had significantly higher levels of
      fidelity than the virtual simulator (p < 0.001) with a large effect size
      difference (Cohen d < 1.3). CONCLUSION: The newly developed fidelity
      questionnaire is a reliable tool that can potentially be used to determine the
      fidelity of other surgical simulators. Increasing the fidelity of this virtual
      simulator is required before its use as a training tool for surgical fixation.
      The virtual simulator brings with it the added benefits of repeated, independent
      safe use with immediate, objective feedback and the potential to alter the
      complexity of the skill.

PMID- 23883512
TI  - Abstracts of the 13th Bethune Round Table Conference on International Surgery.
      May 10-11, 2013. Vancouver, British Columbia, Canada.

PMID- 23883511
TI  - Role of Evidence-Based Reviews in Surgery in teaching critical appraisal skills
      and in journal clubs.
AB  - BACKGROUND: Evidence-Based Reviews in Surgery (EBRS) is a program developed to
      teach critical appraisal skills to general surgeons and residents. The purpose of
      this study was to assess the use of EBRS by general surgery residents across
      Canada and to assess residents' opinions regarding EBRS and journal clubs.
      METHODS: We surveyed postgraduate year 2-5 residents from 15 general surgery
      programs. Data are presented as percentages and means. RESULTS: A total of 231
      residents (58%, mean 56% per program, range 0%-100%) responded: 172 (75%)
      residents indicated that they know about EBRS and that it is used in their
      programs. More than 75% of residents who use EBRS agreed or strongly agreed that
      the EBRS clinical and methodological articles and reviews are relevant. Only 55
      residents (24%) indicated that they used EBRS online. Most residents (198 [86%])
      attend journal clubs. The most common format is a mandatory meeting held at a
      special time every month with faculty members with epidemiological and clinical
      expertise. Residents stated that EBRS articles were used exclusively (13%) or in
      conjunction with other articles (57%) in their journal clubs. Most respondents
      (176 of 193 [91%]) stated that journal clubs are very or somewhat valuable to
      their education. CONCLUSION: The EBRS program is widely used among general
      surgery residents across Canada. Although most residents who use EBRS rate it
      highly, a large proportion are unaware of EBRS online features. Thus, future
      efforts to increase awareness of EBRS online features and increase its
      accessibility are required.

PMID- 23883513
TI  - Abstracts of the Canadian Spine Society Thirteenth Annual Scientific Conference.
      February 27-March 2, 2013. Fairmont Tremblant, Mont-Tremblant, Quebec, Canada.

PMID- 23883514
TI  - Abstracts of the Canadian Surgery Forum 2013. September 17-22. 2013. Ottawa,
      Ontario, Canada.

PMID- 23883515
TI  - The control of CD8+ T cell responses is preserved in perforin-deficient mice and
      released by depletion of CD4+CD25+ regulatory T cells.
AB  - Immune suppression by Treg has been demonstrated in a number of models, but the
      mechanisms of this suppression are only partly understood. Recent work has
      suggested that Tregs may suppress by directly killing immune cell populations in
      vivo in a perforin- and granzyme B-dependent manner. To establish whether
      perforin is necessary for the regulation of immune responses in vivo, we examined
      OVA-specific CD8(+) T cell responses in WT and PKO mice immunized with OVA and
      alpha-GalCer and the expansion of WT OT-I CD8(+) T cells adoptively transferred
      into WT or PKO mice immunized with DC-OVA. We observed similar expansion,
      phenotype, and effector function of CD8(+) T cells in WT and PKO mice, suggesting
      that CD8(+) T cells were subjected to a similar amount of regulation in the two
      mouse strains. In addition, when WT and PKO mice were depleted of Tregs by anti
      CD25 mAb treatment before DC-OVA immunization, CD8(+) T cell proliferation,
      cytotoxicity, and cytokine production were increased similarly, suggesting a
      comparable involvement of CD25(+) Tregs in controlling T cell proliferation and
      effector function in these two mouse strains. These data suggest that perforin
      expression is not required for normal immune regulation in these models of in
      vivo CD8(+) T cell responses induced by immunization with OVA and alpha-GalCer or
      DC-OVA. 

PMID- 23883516
TI  - Biliary obstruction results in PD-1-dependent liver T cell dysfunction and acute
      inflammation mediated by Th17 cells and neutrophils.
AB  - Biliary obstruction is a common clinical problem that is associated with
      intrahepatic inflammation and impaired immunity. PD-1 is well known to mediate T
      cell dysfunction but has been reported to promote and attenuate acute
      inflammation in various injury models. With the use of a well-established murine
      model of BDL, we studied the effects of intrahepatic PD-1 expression on LTC
      function, inflammation, and cholestasis. Following BDL, PD-1 expression increased
      significantly among LTCs. Increased PD-1 expression following BDL was associated
      with decreased LTC proliferation and less IFN-gamma production. Elimination of PD
      1 expression resulted in significantly improved proliferative capacity among LTC
      following BDL, in addition to a more immunostimulatory cytokine profile. Not only
      was LTC function rescued in PD-1(-/-) mice, but also, the degrees of biliary cell
      injury, cholestasis, and inflammation were diminished significantly compared with
      WT animals following BDL. PD-1-mediated acute inflammation following BDL was
      associated with expansions of intrahepatic neutrophil and Th17 cell populations,
      with the latter dependent on IL-6. PD-1 blockade represents an attractive
      strategy for reversing intrahepatic immunosuppression while limiting inflammatory
      liver damage. 

PMID- 23883518
TI  - Oseltamivir effect on antibiotic-treated lower respiratory tract complications in
      virologically positive randomized trial participants.

PMID- 23883517
TI  - AMPKalpha1 deficiency amplifies proinflammatory myeloid APC activity and CD40
      signaling.
AB  - AMPK is a serine/threonine kinase that regulates energy homeostasis and metabolic
      stress in eukaryotes. Previous work from our laboratory, as well as by others,
      has provided evidence that AMPKalpha1 acts as a negative regulator of TLR-induced
      inflammatory function. Herein, we demonstrate that AMPKalpha1-deficient
      macrophages and DCs exhibit heightened inflammatory function and an enhanced
      capacity for antigen presentation favoring the promotion of Th1 and Th17
      responses. Macrophages and DCs generated from AMPKalpha1-deficient mice produced
      higher levels of proinflammatory cytokines and decreased production of the anti
      inflammatory cytokine IL-10 in response to TLR and CD40 stimulation as compared
      with WT cells. In assays of antigen presentation, AMPKalpha1 deficiency in the
      myeloid APC and T cell populations contributed to enhanced IL-17 and IFN-gamma
      production. Focusing on the CD154-CD40 interaction, we found that CD40
      stimulation resulted in increased phosphorylation of ERK1/2, p38, and NF-kappaB
      p65 and decreased activation of the anti-inflammatory Akt -GSK3beta-CREB pathway
      in DCs deficient for AMPKalpha1. Our data demonstrate that AMPKalpha1 serves to
      attenuate LPS and CD40-mediated proinflammatory activity of myeloid APCs and that
      AMPKalpha1 activity in both APC and T cells contributes to T cell functional
      polarization during antigen presentation. 

PMID- 23883519
TI  - Kenyan purple tea anthocyanins ability to cross the blood brain barrier and
      reinforce brain antioxidant capacity in mice.
AB  - Studies on antioxidants as neuroprotective agents have been hampered by the
      impermeability of the blood brain barrier (BBB) to many compounds. However,
      previous studies have shown that a group of tea flavonoids, the catechins, are
      brain permeable and neuroprotective. Despite this remarkable observation, there
      exist no data on the bioavailability and pharmacological benefits of tea
      anthocyanins (ACNs) in the brain tissue. This study investigated the ability of
      Kenyan purple tea ACNs to cross the BBB and boost the brain antioxidant capacity.
      Mice were orally administered with purified and characterized Kenyan purple tea
      ACNs or a combination of Kenyan purple tea ACNs and coenzyme-Q10 at a dose of 200
      mg/kg body weight in an experiment that lasted for 15 days. Twenty-four hours
      post the last dosage of antioxidants, CO2 was used to euthanize the mice after
      which the brain was excised and used for various biochemical analyses. Brain
      extracts were analysed by high-performance liquid chromatography for ACN
      metabolites and spectrophotometry for cellular glutathione (GSH). Kenyan purple
      tea ACNs significantly (P < 0.05) raised brain GSH levels implying boost in brain
      antioxidant capacity. However, co-administration of both antioxidants caused a
      reduction of these beneficial effects implying a negative interaction. Notably,
      ACN metabolites were detected in brain tissue of ACN-fed mice. Our results
      constitute the first demonstration that Kenyan purple tea ACNs can cross the BBB
      reinforcing the brain's antioxidant capacity. Hence, the need to study them as
      suitable candidates for dietary supplements that could support antioxidant
      capacity in the brain and have potential to provide neuroprotection in
      neurodegenerative conditions. 

PMID- 23883520
TI  - Product inhibition of cellulases studied with 14C-labeled cellulose substrates.
AB  - BACKGROUND: As a green alternative for the production of transportation fuels,
      the enzymatic hydrolysis of lignocellulose and subsequent fermentation to ethanol
      are being intensively researched. To be economically feasible, the hydrolysis of
      lignocellulose must be conducted at a high concentration of solids, which results
      in high concentrations of hydrolysis end-products, cellobiose and glucose, making
      the relief of product inhibition of cellulases a major challenge in the process.
      However, little quantitative information on the product inhibition of individual
      cellulases acting on cellulose substrates is available because it is
      experimentally difficult to assess the hydrolysis of the heterogeneous polymeric
      substrate in the high background of added products. RESULTS: The cellobiose and
      glucose inhibition of thermostable cellulases from Acremonium thermophilum,
      Thermoascus aurantiacus, and Chaetomium thermophilum acting on uniformly 14C
      labeled bacterial cellulose and its derivatives, 14C-bacterial microcrystalline
      cellulose and 14C-amorphous cellulose, was studied. Cellulases from Trichoderma
      reesei were used for comparison. The enzymes most sensitive to cellobiose
      inhibition were glycoside hydrolase (GH) family 7 cellobiohydrolases (CBHs),
      followed by family 6 CBHs and endoglucanases (EGs). The strength of glucose
      inhibition followed the same order. The product inhibition of all enzymes was
      relieved at higher temperatures. The inhibition strength measured for GH7 CBHs
      with low molecular-weight model substrates did not correlate with that measured
      with 14C-cellulose substrates. CONCLUSIONS: GH7 CBHs are the primary targets for
      product inhibition of the synergistic hydrolysis of cellulose. The inhibition
      must be studied on cellulose substrates instead of on low molecular-weight model
      substrates when selecting enzymes for lignocellulose hydrolysis. The advantages
      of using higher temperatures are an increase in the catalytic efficiency of
      enzymes and the relief of product inhibition.

PMID- 23883522
TI  - Translational selection frequently overcomes genetic drift in shaping synonymous
      codon usage patterns in vertebrates.
AB  - Synonymous codon usage patterns are shaped by a balance between mutation, drift,
      and natural selection. To date, detection of translational selection in
      vertebrates has proven to be a challenging task, obscured by small long-term
      effective population sizes in larger animals and the existence of isochores in
      some species. The consensus is that, in such species, natural selection is either
      completely ineffective at overcoming mutational pressures and genetic drift or
      perhaps is effective but so weak that it is not detectable. The aim of this
      research is to understand the interplay between mutation, selection, and genetic
      drift in vertebrates. We observe that although variation in mutational bias is
      undoubtedly the dominant force influencing codon usage, translational selection
      acts as a weak additional factor influencing synonymous codon usage. These
      observations indicate that translational selection is a widespread phenomenon in
      vertebrates and is not limited to a few species. 

PMID- 23883521
TI  - Expression and sequence evolution of aromatase cyp19a1 and other sexual
      development genes in East African cichlid fishes.
AB  - Sex determination mechanisms are highly variable across teleost fishes and sexual
      development is often plastic. Nevertheless, downstream factors establishing the
      two sexes are presumably conserved. Here, we study sequence evolution and gene
      expression of core genes of sexual development in a prime model system in
      evolutionary biology, the East African cichlid fishes. Using the available five
      cichlid genomes, we test for signs of positive selection in 28 genes including
      duplicates from the teleost whole-genome duplication, and examine the expression
      of these candidate genes in three cichlid species. We then focus on a
      particularly striking case, the A- and B-copies of the aromatase cyp19a1, and
      detect different evolutionary trajectories: cyp19a1A evolved under strong
      positive selection, whereas cyp19a1B remained conserved at the protein level, yet
      is subject to regulatory changes at its transcription start sites. Importantly,
      we find shifts in gene expression in both copies. Cyp19a1 is considered the most
      conserved ovary-factor in vertebrates, and in all teleosts investigated so far,
      cyp19a1A and cyp19a1B are expressed in ovaries and the brain, respectively. This
      is not the case in cichlids, where we find new expression patterns in two derived
      lineages: the A-copy gained a novel testis-function in the Ectodine lineage,
      whereas the B-copy is overexpressed in the testis of the speciest-richest cichlid
      group, the Haplochromini. This suggests that even key factors of sexual
      development, including the sex steroid pathway, are not conserved in fish,
      supporting the idea that flexibility in sexual determination and differentiation
      may be a driving force of speciation. 

PMID- 23883523
TI  - Divergent expression regulation of gonad development genes in medaka shows
      incomplete conservation of the downstream regulatory network of vertebrate sex
      determination.
AB  - Genetic control of male or female gonad development displays between different
      groups of organisms a remarkable diversity of "master sex-determining genes" at
      the top of the genetic hierarchies, whereas downstream components surprisingly
      appear to be evolutionarily more conserved. Without much further studies,
      conservation of sequence has been equalized to conservation of function. We have
      used the medaka fish to investigate the generality of this paradigm. In medaka,
      the master male sex-determining gene is dmrt1bY, a highly conserved downstream
      regulator of sex determination in vertebrates. To understand its function in
      orchestrating the complex gene regulatory network, we have identified targets
      genes and regulated pathways of Dmrt1bY. Monitoring gene expression and
      interactions by transgenic fluorescent reporter fish lines, in vivo tissue
      chromatin immunoprecipitation and in vitro gene regulation assays revealed
      concordance but also major discrepancies between mammals and medaka, notably
      amongst spatial, temporal expression patterns and regulations of the canonical
      Hedgehog and R-spondin/Wnt/Follistatin signaling pathways. Examination of Foxl2
      protein distribution in the medaka ovary defined a new subpopulation of theca
      cells, where ovarian-type aromatase transcriptional regulation appears to be
      independent of Foxl2. In summary, these data show that the regulation of the
      downstream regulatory network of sex determination is less conserved than
      previously thought. 

PMID- 23883524
TI  - Abundance and distribution of transposable elements in two Drosophila QTL mapping
      resources.
AB  - Here we present computational machinery to efficiently and accurately identify
      transposable element (TE) insertions in 146 next-generation sequenced inbred
      strains of Drosophila melanogaster. The panel of lines we use in our study is
      composed of strains from a pair of genetic mapping resources: the Drosophila
      Genetic Reference Panel (DGRP) and the Drosophila Synthetic Population Resource
      (DSPR). We identified 23,087 TE insertions in these lines, of which 83.3% are
      found in only one line. There are marked differences in the distribution of
      elements over the genome, with TEs found at higher densities on the X chromosome,
      and in regions of low recombination. We also identified many more TEs per base
      pair of intronic sequence and fewer TEs per base pair of exonic sequence than
      expected if TEs are located at random locations in the euchromatic genome. There
      was substantial variation in TE load across genes. For example, the paralogs
      derailed and derailed-2 show a significant difference in the number of TE
      insertions, potentially reflecting differences in the selection acting on these
      loci. When considering TE families, we find a very weak effect of gene family
      size on TE insertions per gene, indicating that as gene family size increases the
      number of TE insertions in a given gene within that family also increases. TEs
      are known to be associated with certain phenotypes, and our data will allow
      investigators using the DGRP and DSPR to assess the functional role of TE
      insertions in complex trait variation more generally. Notably, because most TEs
      are very rare and often private to a single line, causative TEs resulting in
      phenotypic differences among individuals may typically fail to replicate across
      mapping panels since individual elements are unlikely to segregate in both
      panels. Our data suggest that "burden tests" that test for the effect of TEs as a
      class may be more fruitful. 

PMID- 23883525
TI  - Exercise rehabilitation for patients with critical illness: a randomized
      controlled trial with 12 months of follow-up.
AB  - INTRODUCTION: The purpose of this trial was to investigate the effectiveness of
      an exercise rehabilitation program commencing during ICU admission and continuing
      into the outpatient setting compared with usual care on physical function and
      health-related quality of life in ICU survivors. METHODS: We conducted a single
      center, assessor-blinded, randomized controlled trial. One hundred and fifty
      participants were stratified and randomized to receive usual care or intervention
      if they were in the ICU for 5 days or more and had no permanent neurological
      insult. The intervention group received intensive exercises in the ICU and the
      ward and as outpatients. Participants were assessed at recruitment, ICU
      admission, hospital discharge and at 3-, 6- and 12-month follow-up. Physical
      function was evaluated using the Six-Minute Walk Test (6MWT) (primary outcome),
      the Timed Up and Go Test and the Physical Function in ICU Test. Patient-reported
      outcomes were measured using the Short Form 36 Health Survey, version 2 (SF-36v2)
      and Assessment of Quality of Life (AQoL) Instrument. Data were analyzed using
      mixed models. RESULTS: The a priori enrollment goal was not reached. There were
      no between-group differences in demographic and hospital data, including acuity
      and length of acute hospital stay (LOS) (Acute Physiology and Chronic Health
      Evaluation II score: 21 vs 19; hospital LOS: 20 vs 24 days). No significant
      differences were found for the primary outcome of 6MWT or any other outcomes at
      12 months after ICU discharge. However, exploratory analyses showed the rate of
      change over time and mean between-group differences in 6MWT from first assessment
      were greater in the intervention group. CONCLUSIONS: Further research examining
      the trajectory of improvement with rehabilitation is warranted in this
      population. TRIAL REGISTRATION: The trial was registered with the Australian New
      Zealand Clinical Trials Registry ACTRN12605000776606.

PMID- 23883527
TI  - The influence of phosphorus content on magnetic anisotropy in ferromagnetic (Ga,
      Mn) (As, P)/GaAs thin films.
AB  - The magnetic anisotropy of the ferromagnetic semiconductor (Ga, Mn) (As, P) is
      studied in a material-specific microscopic k ?p approach. We calculate the
      electronic energy band structure of (Ga, Mn) (As, P) quaternary ferromagnetic
      alloys using a 40-band k ?p model and taking into account the s, p-d exchange
      interaction and the strain of the (Ga, Mn) (As, P) layer on a GaAs substrate. We
      determine the variations of the carrier effective masses in the strained (Ga, Mn)
      (As, P)/GaAs system. The magnetic anisotropy constants obtained from our
      simulations using a mean-field model are compared with the experimental ones
      determined by ferromagnetic resonance spectroscopy on a set of samples with
      constant manganese concentration and varying phosphorus concentration. An
      excellent quantitative agreement between experiment and theory is found for the
      uniaxial out-of-plane and cubic in-plane anisotropy parameters. 

PMID- 23883526
TI  - Bulk milk ELISA and the diagnosis of parasite infections in dairy herds: a
      review.
AB  - The bulk milk enzyme-linked immune sorbent assay (ELISA) is a rapid and
      inexpensive method of assessing herd exposure to pathogens that is increasingly
      being used for the diagnosis of parasite infections in dairy herds. In this
      paper, with the dairy herd health veterinarian in mind, we review the principles
      of the assay and the recent literature on the potential role of bulk milk ELISA
      for the diagnosis of ostertagiosis, fasciolosis, parasitic bronchitis due to
      cattle lung worm and neosporosis. It is generally accepted that assay results
      reflect exposure to the parasite rather than the presence of active infection.
      Bulk milk ELISA can be a useful tool for the veterinary practitioner as a
      component of a herd health monitoring programme or in the context of a herd
      health investigation. It can also play a role in regional or national
      surveillance programmes. However, the results need to be interpreted within the
      context of the herd-specific health management, the milk production pattern and
      the parasite life cycle. 

PMID- 23883528
TI  - Clinical and demographic covariates of chronic opioid and non-opioid analgesic
      use in rural-dwelling older adults: the MoVIES project.
AB  - BACKGROUND: To describe covariates and patterns of late-life analgesic use in the
      rural, population-based MoVIES cohort from 1989 to 2002. METHODS: Secondary
      analysis of epidemiologic survey of elderly people conducted over six biennial
      assessment waves. Potential covariates of analgesic use included age, gender,
      depression, sleep, arthritis, smoking, alcohol, and general health status. Of the
      original cohort of 1,681, this sample comprised 1,109 individuals with complete
      data on all assessments. Using trajectory analysis, participants were
      characterized as chronic or non-chronic users of opioid and non-opioid
      analgesics. Multivariable regression was used to model predictors of chronic
      analgesic use. RESULTS: The cohort was followed for mean (SD) 7.3 (2.7) years.
      Chronic use of opioid analgesics was reported by 7.2%, while non-opioid use was
      reported by 46.1%. In the multivariable model, predictors of chronic use of both
      opioid and non-opioid analgesics included female sex, taking >=2 prescription
      medications, and "arthritis" diagnoses. Chronic opioid use was also associated
      with age 75-84 years; chronic non-opioid use was also associated with sleep
      continuity disturbance. CONCLUSIONS: These epidemiological data confirm clinical
      observations and generate hypotheses for further testing. Future studies should
      investigate whether addressing sleep problems might lead to decreased use of non
      opioid analgesics and possibly enhanced pain management.

PMID- 23883529
TI  - Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia
      associated with endometriosis.
AB  - Nerve growth factor (NGF) has been recently proposed as one of the key factors
      responsible not only for promotion of nerve fiber growth but also for the onset
      and maintenance of pain in a variety of diseases. The aim of this study was to
      investigate the role of NGF in the pelvic pain associated with endometriosis.
      Tissue and peritoneal fluid samples were collected from 95 women with
      laparoscopically and histopathologically confirmed endometriosis and 59 control
      women without endometriosis. Expression levels of NGF mRNA and protein were
      examined using real-time RT-PCR and immunohistochemistry, respectively.
      Concentration of NGF in the peritoneal fluid (PF-NGF) was measured using ELISA.
      The degree of dyspareunia and dysmenorrhea was evaluated using a verbal rating
      scale. Real-time RT-PCR analysis revealed that NGF mRNA was significantly more
      abundant in the ovarian endometriomas and peritoneal endometriosis than in the
      normal control endometrium. Immunohistochemical analyses demonstrated that NGF
      was prominently expressed and preferentially localized to the glands of the
      ovarian endometriomas and peritoneal endometriosis, whereas it was only weakly
      detectable in the normal endometrium. Although PF-NGF was undetectable in some
      normal subjects and endometriosis patients, elevated PF-NGF in the peritoneal
      fluid was more frequently observed in endometriosis patients with severe pain
      than in those with less severe pain. Our results suggest that NGF produced
      locally in the peritoneal cavity may be involved in the generation of
      endometriosis-associated pelvic pain. 

PMID- 23883530
TI  - Predicting the progression of geographic atrophy in age-related macular
      degeneration with SD-OCT en face imaging of the outer retina.
AB  - BACKGROUND AND OBJECTIVE: Spectral-domain optical coherence tomography (SD-OCT)
      en face imaging was used to measure the growth of geographic atrophy (GA) and
      identify baseline anatomic changes in the outer retina in eyes with nonexudative
      age-related macular degeneration (AMD). PATIENTS AND METHODS: In this prospective
      study, eyes were imaged using 200 * 200 and 512 * 128 A-scan raster patterns.
      Outer retinal anatomy was visualized using en face imaging of a 20-MUm thick slab
      encompassing the inner segment/outer segment (IS/OS) band. RESULTS: En face SD
      OCT imaging of the IS/OS region revealed a bilaterally symmetrical pattern of
      outer retinal disruption extending beyond the borders of GA that accurately
      predicted the progression of GA over 1 year in 13 of 30 eyes (43.3%). In the
      remaining cases, the area of disruption was much larger than the area of
      progression. CONCLUSION: En face imaging of the outer retina can predict the
      growth of GA in some eyes. Due to the bilateral symmetry of these findings, this
      imaging strategy may identify a genetic subset of patients in whom photoreceptor
      loss precedes the progression of GA. These areas with outer retinal disruption
      should be followed in clinical trials designed to test treatments for dry AMD.

PMID- 23883531
TI  - Comparative study of corneal wetting agents during 25-gauge microincision
      vitrectomy surgery under a noncontact wide-angle viewing system.
AB  - BACKGROUND AND OBJECTIVE: To compare the effects of corneal wetting agents during
      25-gauge microincision vitrectomy surgery (MIVS) under a binocular indirect
      ophthalmic microscope system. MATERIALS AND METHODS: This prospective,
      randomized, comparative study included 45 eyes undergoing 25-gauge MIVS. The
      randomly assigned corneal wetting agents were balanced salt solution, ProVisc,
      and DisCoVisc. The main outcome measures were the frequency of applications, the
      duration of each application, and the corneal surface status including corneal
      fluorescein staining score postoperatively. RESULTS: The mean frequency of
      applications was higher for balanced salt solution (13.6 +/- 4.3) than ProVisc
      (2.7 +/- 1.0) or DisCoVisc (1.7 +/- 0.5) (P < .001). The duration of each
      application was longer for DisCoVisc (29.8 +/- 6.0 minutes) than balanced salt
      solution (3.7 +/- 1.1 minutes) or ProVisc (17.6 +/- 3.6 minutes) (P < .001). The
      fluorescein staining score was higher for balanced salt solution until 7 days
      postoperatively (P < .001). CONCLUSION: ProVisc and DisCoVisc could be more
      effective corneal wetting agents than balanced salt solution by minimizing the
      frequency of intraoperative application and postoperative corneal injury.

PMID- 23883532
TI  - Pars plana vitrectomy with multiple transvenous chorioretinotomies for macular
      edema due to retinal vein occlusion.
AB  - BACKGROUND AND OBJECTIVE: To review results of vitreous surgery for branch and
      central retinal vein occlusion (BRVO and CRVO). PATIENTS AND METHODS: All cases
      of vitrectomy with multiple transvenous chorioretinotomies for retinal vein
      occlusion at a vitreoretinal subspecialty practice were reviewed. RESULTS: Twenty
      eyes of 20 patients (four with BRVO and 16 with CRVO) were included. Mean time
      from diagnosis to surgery was 15 months, and mean postoperative follow-up was 22
      months. Injections of bevacizumab or ranibizumab decreased postoperatively (P <
      .0001; Poisson regression model), while log-MAR visual acuity improved (P =
      .0396; Wilcoxon signed-rank test). Ten eyes required no further injections
      postoperatively, and three eyes required one postoperative injection. Macular
      edema expressed as OCT maximum macular thickness was significantly reduced
      postoperatively at 6 months and 12 months (P = .0077 and .0093, respectively).
      CONCLUSION: In a pilot study of retinal vein occlusion treatment, multiple
      transvenous chorioretinotomy surgery significantly improved visual acuity and
      macular edema and reduced intravitreal drug dependency. Further study is
      warranted.

PMID- 23883533
TI  - In vivo detection of hESC-RPE cells via confocal near-infrared fundus
      reflectance.
AB  - BACKGROUND AND OBJECTIVE: To investigate whether the confocal near-infrared
      reflectance (NIR) imaging modality could detect the in vivo presence of retinal
      pigment epithelium cells derived from embryonic human stem cells (hESC-RPE)
      implanted into the subretinal space of the Royal College of Surgeons (RCS) rat.
      MATERIALS AND METHODS: Monthly NIR images were obtained from RCS rats implanted
      with either hESC-RPE seeded on a parylene membrane (n = 14) or parylene membrane
      without cells (n = 14). Two independent, masked investigators graded the images.
      Histology and immunohistochemistry were performed at different time points (150,
      210, and 270 postnatal days of age). RESULTS: NIR images revealed that an average
      of 20.53% of the parylene membrane area was covered by hESC-RPE. RPE-65 and TRA-1
      85 confirmed the presence of human-specific RPE cells in those animals. No areas
      corresponding to cells were found in the group implanted with membrane only.
      Intergrader agreement was high (r = 0.89-0.92). CONCLUSION: The NIR mode was
      suitable to detect the presence of hESC-RPE seeded on a membrane and implanted
      into the subretinal space of the RCS rat.

PMID- 23883534
TI  - Fundus autofluorescence in ampiginous choroiditis.
AB  - Fundus autofluorescence (FAF) is being increasingly employed in the evaluation of
      retinal diseases. We report the first description of FAF findings during the
      natural history of ampiginous choroiditis and correlate these findings to fundus
      photography, infrared imaging, and cross-sectional optical coherence tomography.
      In a patient with a 12-month recurring, relapsing course of ampiginous
      choroiditis, there was a predictable pattern of FAF findings. At the time of
      presentation with a whitish-yellow, creamy clinical lesion, FAF reveals a
      diffuse, subtle hyperautofluorescence at the site of activity. As the clinical
      lesion fades, the FAF takes on a more intense, discrete, coalesced
      hyperautofluorescence, which decreases and becomes stippled over time, eventually
      giving way to a patch of hypoautofluorescence at the site of inactivity.
      Examination over the patient's long course suggests that FAF evolves predictably
      during exacerbations and remissions, and the FAF findings reveal activity well
      after the clinical lesion resolves. FAF is a simple, noninvasive, and effective
      modality for following the evolution of ampiginous choroiditis.

PMID- 23883535
TI  - Retinal pigment epithelial detachment in ABCA4-associated Stargardt's disease.
AB  - The authors describe bilateral and sequential pigment epithelial detachment (PED)
      formation in a 16-year-old girl with ABCA4-associated Stargardt's disease
      (STGD1). On routine examination, a new large PED was observed in the left eye
      with late leakage evident on fluorescein angiography suggestive of possible
      occult choroidal neovascularization. The lesion was therefore treated with
      bevacizumab, but with no involutional lesion response. Months later, a similar
      lesion appeared in the right eye. The authors believe this to be the first
      reported case of acute bilateral and sequential PED development in a patient with
      ABCA4-associated STGD1. Optical coherence tomography-guided morphological
      analysis of lesion development in ABCA4 disease with documentation of PED
      formation may suggest a plausible role for disruption at the level of Bruch's
      membrane in the pathophysiology of STGD1.

PMID- 23883536
TI  - Focal choroidal excavation associated with polypoidal choroidal vasculopathy.
AB  - A 48-year-old woman presented with blurred vision in her right eye for 6 weeks.
      Visual acuity was 20/300 and 20/25 in the right and left eyes, respectively.
      Fundus examination showed subretinal hemorrhage in the superonasal macula in the
      right eye, whereas the left eye was normal. Fluorescein angiography showed
      blocked fluorescence from hemorrhage and a round distinct hypofluorescent spot
      along the inferotemporal arcade. Indocyanine green angiography revealed
      hyperfluorescent tubular and aneurysmal dilatations consistent with polypoidal
      choroidal vasculopathy in the superior macula. Spectral-domain optical coherence
      tomography showed retinal pigment epithelial irregularities and detachment. Scans
      through the round area of hypofluorescence revealed a conforming focal choroidal
      excavation and thinning of the underlying choriocapillaries. Because the
      pathogenesis of focal choroidal excavation is currently unclear, the authors
      propose the possibility of an acquired etiology related to loss of
      choriocapillaries from perfusion abnormalities as evidenced here.

PMID- 23883537
TI  - Pars plana vitrectomy for rhegmatogenous retinal detachment associated with
      benign retinal tumors.
AB  - Two patients with known histories of benign retinal tumors presented with
      rhegmatogenous retinal detachments (RRD) in the same eye. One had a retinocytoma
      and presenting vision of 20/50, while the other had congenital hypertrophy of the
      retinal pigment epithelium and vision of 20/30. Both had subretinal fluid
      accumulation in a configuration consistent with a retinal break near the tumor;
      however, no breaks were detected on examination or intraoperatively. Pars plana
      vitrectomy (PPV), drainage retinotomy, fluid-air exchange, barrier laser around
      the tumor, and gas tamponade successfully reattached the retina in both cases.
      After 12 and 6 months of follow-up, respectively, final vision was 20/25 and the
      retina remained attached. RRD may be associated with benign retinal tumors
      presumably with microscopic breaks at the margins. In these cases, PPV, drainage
      retinotomy, fluid-air exchange, endolaser around the tumor, and gas tamponade can
      be effective for treatment.

PMID- 23883538
TI  - "Floater scotoma" demonstrated on spectral-domain optical coherence tomography
      and caused by vitreous opacification.
AB  - Patients with prominent vitreous opacities may demonstrate a characteristic
      shadowing on the volume-scanning protocols using spectral-domain optical
      coherence tomography. The authors present five cases of this characteristic
      shadowing artifact. This finding may be useful in objectively documenting the
      status of vitreous opacification and verifying the patient's complaint of
      symptomatic floaters, a so-called "floater scotoma".

PMID- 23883539
TI  - "My body's a 50 year-old but my brain is definitely an 85 year-old": exploring
      the experiences of men ageing with HIV-associated neurocognitive challenges.
AB  - INTRODUCTION: Research investigating HIV, neurocognition and ageing is well
      developed using neuropsychometric or other quantitative approaches; however,
      little is known about individuals' subjective experiences. The purpose of this
      article is to explore the experiences of men aged 50 and older who self-identify
      as having HIV-associated neurocognitive challenges. In particular, this study
      uses the Episodic Disability Framework (EDF) to explore participants' perceptions
      regarding: 1) symptoms/impairments, difficulties with day-to-day activities,
      challenges with social inclusion and uncertainty; 2) ageing as related to their
      HIV-associated neurocognitive challenges, and 3) the episodic nature of their HIV
      associated neurocognitive challenges. METHODS: This qualitative, interpretive
      study involved in-depth, semi-structured interviews with 12 men aged 50 years and
      older who self-identified as having HIV-associated neurocognitive challenges.
      Participants were recruited from a neurobehavioural research unit (NBRU) at a
      large hospital in Toronto, Canada. Data were analyzed thematically and with
      reference to the EDF. RESULTS: Participants' experiences reflected all concepts
      within the EDF to some extent. Difficulties with daily activities were diverse
      but were addressed using similar living strategies. Participants described
      challenges with work and social relationships resulting from neurocognitive
      challenges. Participants downplayed the significance of uncertainty in their
      lives, which they attributed to effective living strategies. Most men reported
      confusion regarding the link between their neurocognitive challenges and ageing.
      Others discussed ageing as an asset that helped with coping. CONCLUSIONS: This is
      the first study to use a disability framework to examine the subjective
      experiences of men ageing with HIV-associated neurocognitive challenges. Findings
      reframe the episodic disability experienced by these individuals as being
      predictably linked to certain triggers. As such, support for managing
      neurocognitive challenges could focus on triggers that exacerbate the condition
      in addition to the impairments themselves. The study also describes ageing as not
      only a source of problems but also as an asset among men growing older with HIV.

PMID- 23883540
TI  - Selecting beta-glucosidases to support cellulases in cellulose saccharification.
AB  - BACKGROUND: Enzyme end-product inhibition is a major challenge in the hydrolysis
      of lignocellulose at a high dry matter consistency. beta-glucosidases (BGs)
      hydrolyze cellobiose into two molecules of glucose, thereby relieving the product
      inhibition of cellobiohydrolases (CBHs). However, BG inhibition by glucose will
      eventually lead to the accumulation of cellobiose and the inhibition of CBHs.
      Therefore, the kinetic properties of candidate BGs must meet the requirements
      determined by both the kinetic properties of CBHs and the set-up of the
      hydrolysis process. RESULTS: The kinetics of cellobiose hydrolysis and glucose
      inhibition of thermostable BGs from Acremonium thermophilum (AtBG3) and
      Thermoascus aurantiacus (TaBG3) was studied and compared to Aspergillus sp. BG
      purified from Novozyme(r)188 (N188BG). The most efficient cellobiose hydrolysis
      was achieved with TaBG3, followed by AtBG3 and N188BG, whereas the enzyme most
      sensitive to glucose inhibition was AtBG3, followed by TaBG3 and N188BG. The use
      of higher temperatures had an advantage in both increasing the catalytic
      efficiency and relieving the product inhibition of the enzymes. Our data,
      together with data from a literature survey, revealed a trade-off between the
      strength of glucose inhibition and the affinity for cellobiose; therefore,
      glucose-tolerant BGs tend to have low specificity constants for cellobiose
      hydrolysis. However, although a high specificity constant is always an advantage,
      in separate hydrolysis and fermentation, the priority may be given to a higher
      tolerance to glucose inhibition. CONCLUSIONS: The specificity constant for
      cellobiose hydrolysis and the inhibition constant for glucose are the most
      important kinetic parameters in selecting BGs to support cellulases in cellulose
      hydrolysis.

PMID- 23883541
TI  - Vitamin D supplementation restores suppressed synaptic plasticity in Alzheimer's
      disease.
AB  - OBJECTIVES: Hippocampus, an appropriate area of brain for assessment of long-term
      potentiation (LTP), has been found to be susceptible to neural damages caused by
      Alzheimer's disease. Evidence indicates that vitamin D supports nerve
      transmission and synaptic plasticity. Vitamin D receptors are expressed in the
      hippocampus. METHODS: The present study evaluates occurrence of LTP in the
      control (CON) group fed with normal regimen and, three groups of Abeta-treated
      rats taking normal (ALZ), vitamin D-free (ALZ - D), or 1,25(OH)2D3 supplemented
      (ALZ + D) food regimens. In in vivo experiments pre- and post-tetanus field
      extracellular postsynaptic potentials (fEPSPs) were recorded in the CA3-CA1
      pathway. RESULTS: We found that the amplitude of baseline fEPSPs was
      significantly lower in the ALZ group compared with the CON one; lack of vitamin D
      further declined the amplitude of responses in the ALZ - D animals. While the
      tetanic stimulation elicited a considerable LTP in the CON rats it was failed to
      induce LTP in the ALZ animals. Furthermore, the tetanus considerably depressed
      the amplitude of recordings in the ALZ - D group. 1,25(OH)2D3 supplementation
      restored post-tetanus potentiation of fEPSPs amplitude in the ALZ + D groups.
      DISCUSSION: The present findings signify the crucial role of vitamin D on the
      basic synaptic transmission and synaptic plasticity.

PMID- 23883542
TI  - Emergent use of Twitter in the 2011 Tohoku Earthquake.
AB  - INTRODUCTION: Social networks play an important role in disaster situations as
      they have become a new form of social convergence that provides collective
      information. The effect of social media on people who experienced disaster should
      be assessed. Hypothesis In this study, Twitter communication during the Great
      East Japan Earthquake of March 11, 2011 was assessed. The hypothesis of this
      study was that usage of Twitter had psychological effects on victims of the
      disaster. METHODS: A cross-sectional questionnaire survey was carried out in
      cooperation with a major Japanese newspaper three months after the disaster, and
      1,144 volunteer participants responded. They were asked about their health, area
      of residence, property damage they had experienced, information sources they used
      at the time of the disaster, and their usage of Twitter. Further, the Twitter
      users were divided into two groups-with and without disaster experience. Their
      psychological effects relating to feelings of relief, stress or anxiety that they
      experienced in using Twitter were compared between two groups, and Twitter's
      psychological risk of disaster experience was estimated as an odds ratio.
      RESULTS: Twitter users in this study tended to reside in disaster-affected areas
      and thought Twitter was a credible information source during the time of the
      disaster. The psychological effect of Twitter differed based on participants'
      disaster experience and gender. Females with disaster experience reported more
      feelings of relief and stress as a result of using Twitter compared to females
      who did not experience the disaster. On the other hand, males with disaster
      experience only reported more stress experiences as a result of using Twitter
      compared to those without disaster experience. CONCLUSION: Twitter users with
      disaster experience had a higher usage of Twitter than those without disaster
      experience. Social media might have had a material psychological influence on
      people who experienced disaster, and the effect differed by gender. Regardless of
      gender, negative feelings were transmitted easily among people who experienced
      the disaster. It was anticipated that the application of Twitter in a disaster
      situation will be expanded further by taking these findings into consideration.

PMID- 23883543
TI  - A closed-loop neurobotic system for fine touch sensing.
AB  - OBJECTIVE: Fine touch sensing relies on peripheral-to-central neurotransmission
      of somesthetic percepts, as well as on active motion policies shaping tactile
      exploration. This paper presents a novel neuroengineering framework for robotic
      applications based on the multistage processing of fine tactile information in
      the closed action-perception loop. APPROACH: The integrated system modules focus
      on (i) neural coding principles of spatiotemporal spiking patterns at the
      periphery of the somatosensory pathway, (ii) probabilistic decoding mechanisms
      mediating cortical-like tactile recognition and (iii) decision-making and low
      level motor adaptation underlying active touch sensing. We probed the resulting
      neural architecture through a Braille reading task. MAIN RESULTS: Our results on
      the peripheral encoding of primary contact features are consistent with
      experimental data on human slow-adapting type I mechanoreceptors. They also
      suggest second-order processing by cuneate neurons may resolve perceptual
      ambiguities, contributing to a fast and highly performing online discrimination
      of Braille inputs by a downstream probabilistic decoder. The implemented
      multilevel adaptive control provides robustness to motion inaccuracy, while
      making the number of finger accelerations covariate with Braille character
      complexity. The resulting modulation of fingertip kinematics is coherent with
      that observed in human Braille readers. SIGNIFICANCE: This work provides a basis
      for the design and implementation of modular neuromimetic systems for fine touch
      discrimination in robotics.

PMID- 23883544
TI  - Renal insufficiency without albuminuria is associated with peripheral artery
      atherosclerosis and lipid metabolism disorders in patients with type 2 diabetes.
AB  - AIMS: A high prevalence of a low glomerular filtration rate (GFR) has recently
      been reported in patients with diabetes without albuminuria. We aimed to clarify
      the clinical characteristics of such patients, including the associations between
      these characteristics and atherosclerosis. METHODS: We investigated the
      correlations between the estimated GFR (eGFR) and lipid profiles, the ankle
      brachial index (ABI) and the intima-media thickness (IMT) in 450 patients with
      type 2 diabetes without macroalbuminuria. RESULTS: The prevalence of renal
      insufficiency (RI) (GFR <60 mL/min/1.73 m(2)) in the patients without albuminuria
      was 19.1%. The ABI values of the patients with RI were significantly lower than
      those of the patients without RI, regardless of the presence of microalbuminuria,
      while there were no significant differences in IMT between the patients with and
      without RI. In a multivariate analysis, a low ABI was found to be significantly
      associated with a low eGFR, independent of age, sex, smoking, history of
      hypertension and/or dyslipidemia and duration of diabetes (beta=0.134, p=0.013),
      whereas no significant associations were observed between the ABI and the urinary
      albumin excretion rate (UAER). The ApoB/LDL-C ratios and levels of ApoC3 were
      significantly higher in the patients with RI than those observed in the patients
      without RI, regardless of the presence of albuminuria. CONCLUSIONS: RI without
      albuminuria is closely associated with atherosclerosis of the peripheral arteries
      in diabetic patients. Furthermore, alterations in lipid metabolism may underlie
      this association.

PMID- 23883545
TI  - Comprehensive risk management for the prevention of cardiovascular disease:
      executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the
      diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan --
      2012.

PMID- 23883546
TI  - Effects of weight reduction therapy on obstructive sleep apnea syndrome and
      arterial stiffness in patients with obesity and metabolic syndrome.
AB  - AIM: Obesity and metabolic syndrome (MetS) and obstructive sleep apnea (OSA),
      which are often accompanied by obesity, are each independently associated with
      cardiovascular disease (CVD). However, the influence of OSA on arterial stiffness
      in obese patients remains unclear. We herein examined the relationships between
      the severity of OSA and CVD risk factors, including the severity of MetS and
      arterial stiffness, in obese patients. In addition, we evaluated the effects of
      weight reduction therapy on OSA and arterial stiffness. METHODS: Among the 60
      overweight or obese Japanese outpatients enrolled, 46 (76.7%) met the MetS
      criteria. RESULTS: The apnea-hypopnea index (AHI) and cardio-ankle vascular index
      (CAVI), a new index of arterial stiffness, were significantly higher in the MetS
      patients than in the non-MetS patients, whereas there were no significant
      differences in body mass index, blood pressure or the low-density lipoprotein
      cholesterol level. A multivariate regression analysis revealed that waist
      circumference, the C-reactive protein level and CAVI were independently
      correlated with AHI. In addition, age, SBP, IRI and AHI were independently
      correlated with CAVI. Furthermore, weight reduction therapy, including diet and
      exercise, over a three-month period significantly decreased the AHI and CAVI
      values in parallel with a reduction in BMI. CONCLUSIONS: This study demonstrated
      that the severity of OSA is significantly correlated with the severity of MetS
      and arterial stiffness in obese patients. Short-term weight reduction therapy
      improves not only metabolic dysfunction, but also the severity of OSA and
      arterial stiffness, as measured according to the CAVI. Such changes may help to
      prevent atherosclerosis in obese patients.

PMID- 23883547
TI  - Meta-analysis of alcohol price and income elasticities - with corrections for
      publication bias.
AB  - BACKGROUND: This paper contributes to the evidence-base on prices and alcohol use
      by presenting meta-analytic summaries of price and income elasticities for
      alcohol beverages. The analysis improves on previous meta-analyses by correcting
      for outliers and publication bias. METHODS: Adjusting for outliers is important
      to avoid assigning too much weight to studies with very small standard errors or
      large effect sizes. Trimmed samples are used for this purpose. Correcting for
      publication bias is important to avoid giving too much weight to studies that
      reflect selection by investigators or others involved with publication processes.
      Cumulative meta-analysis is proposed as a method to avoid or reduce publication
      bias, resulting in more robust estimates. The literature search obtained 182
      primary studies for aggregate alcohol consumption, which exceeds the database
      used in previous reviews and meta-analyses. RESULTS: For individual beverages,
      corrected price elasticities are smaller (less elastic) by 28-29 percent compared
      with consensus averages frequently used for alcohol beverages. The average price
      and income elasticities are: beer, -0.30 and 0.50; wine, -0.45 and 1.00; and
      spirits, -0.55 and 1.00. For total alcohol, the price elasticity is -0.50 and the
      income elasticity is 0.60. CONCLUSIONS: These new results imply that attempts to
      reduce alcohol consumption through price or tax increases will be less effective
      or more costly than previously claimed.

PMID- 23883548
TI  - CD8+ T-cell counts: an early predictor of risk and mortality in critically ill
      immunocompromised patients with invasive pulmonary aspergillosis.
AB  - INTRODUCTION: Critically ill immunocompromised (CIIC) patients with pulmonary
      infection are a population at high risk for invasive pulmonary aspergillosis
      (IPA). The host defenses are important factors to consider in determining the
      risk and outcome of infection. Quantification of changes in the status of host
      immunity could be valuable for clinical diagnosis and outcome prediction.
      METHODS: We evaluated the quantitative changes in key humoral and cellular
      parameters in CIIC patients with pulmonary infection and their potential
      influence on the risk and prognosis of IPA. We monitored the evolution of these
      parameters in 150 CIIC patients with pulmonary infection on days 1, 3 and 10 (D1,
      D3 and D10) following ICU admission. The primary outcome was 28-day mortality.
      Follow-up included 60- and 90-day mortality. RESULTS: Among the 150 CIIC patients
      included in this study, 62 (41.3%) had microbiological evidence of IPA. Compared
      with patients without IPA, CD3+, CD8+, CD28+CD4+ and CD28+CD8+ CD28+CD8+ T-cell
      counts (D1, D3 and D10) and B-cell counts (D1 and D3) were significantly reduced
      in patients with IPA (P < 0.05). Multivariate regression analysis revealed that
      CD8+ (D3 and D10) (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.23 to
      0.46; OR 0.68, 95% CI 0.56 to 0.80), CD28+CD8+ (D3) (OR 0.73, 95% CI 0.61 to
      0.86) and CD3+ (D10) (OR 0.81, 95% CI 0.63 to 0.98) T-cell counts were
      independent predictors of IPA in CIIC patients. Receiver operating characteristic
      analysis of immune parameters predicting 28-day mortality revealed area under the
      curve values of 0.82 (95% CI 0.71 to 0.92), 0.94 (95% CI 0.87 to 0.99), and 0.94
      (95% CI 0.85 to 0.99) for CD8+ T-cell counts (D1, D3 and D10, respectively) and
      0.84 (95% CI 0.75 to 0.94), 0.92 (95% CI 0.85 to 0.99) and 0.90 (95% CI 0.79 to
      0.99) for CD28+CD8+ T-cell counts (D1, D3 and D10, respectively). Kaplan-Meier
      survival analysis provided evidence that CD8+ and CD28+CD8+ T-cell counts (<149.5
      cells/mm3 and <75 cells/mm3, respectively) were associated with early mortality
      in CIIC patients with IPA (logrank test; P < 0.001). CONCLUSIONS: CD8+ and
      CD28+CD8+ T-cell counts were significantly lower in CIIC patients with IPA than
      in non-IPA patients. Lower CD8+ and CD28+CD8+ T-cell counts in CIIC patients with
      pulmonary infection were associated with higher risk and early mortality in IPA
      and may be valuable for clinical diagnosis and outcome prediction.

PMID- 23883549
TI  - Integrated OMICS guided engineering of biofuel butanol-tolerance in
      photosynthetic Synechocystis sp. PCC 6803.
AB  - BACKGROUND: Photosynthetic cyanobacteria have been recently proposed as a
      'microbial factory' to produce butanol due to their capability to utilize solar
      energy and CO2 as the sole energy and carbon sources, respectively. However, to
      improve the productivity, one key issue needed to be addressed is the low
      tolerance of the photosynthetic hosts to butanol. RESULTS: In this study, we
      first applied a quantitative transcriptomics approach with a next-generation RNA
      sequencing technology to identify gene targets relevant to butanol tolerance in a
      model cyanobacterium Synechocystis sp. PCC 6803. The results showed that 278
      genes were induced by the butanol exposure at all three sampling points through
      the growth time course. Genes encoding heat-shock proteins, oxidative stress
      related proteins, transporters and proteins involved in common stress responses,
      were induced by butanol exposure. We then applied GC-MS based metabolomics
      analysis to determine the metabolic changes associated with the butanol exposure.
      The results showed that 46 out of 73 chemically classified metabolites were
      differentially regulated by butanol treatment. Notably, 3-phosphoglycerate,
      glycine, serine and urea related to general stress responses were elevated in
      butanol-treated cells. To validate the potential targets, we constructed gene
      knockout mutants for three selected gene targets. The comparative phenotypic
      analysis confirmed that these genes were involved in the butanol tolerance.
      CONCLUSION: The integrated OMICS analysis provided a comprehensive view of the
      complicated molecular mechanisms employed by Synechocystis sp. PCC 6803 against
      butanol stress, and allowed identification of a series of potential gene
      candidates for tolerance engineering in cyanobacterium Synechocystis sp. PCC
      6803.

PMID- 23883551
TI  - Oxygen adsorption on the Al9Co2(001) surface: first-principles and STM study.
AB  - Atomic oxygen adsorption on a pure aluminum terminated Al9Co2(001) surface is
      studied by first-principle calculations coupled with STM measurements. Relative
      adsorption energies of oxygen atoms have been calculated on different surface
      sites along with the associated STM images. The local electronic structure of the
      most favourable adsorption site is described. The preferential adsorption site is
      identified as a 'bridge' type site between the cluster entities exposed at the
      (001) surface termination. The Al-O bonding between the adsorbate and the
      substrate presents a covalent character, with s-p hybridization occurring between
      the states of the adsorbed oxygen atom and the aluminum atoms of the surface. The
      simulated STM image of the preferential adsorption site is in agreement with
      experimental observations. This work shows that oxygen adsorption generates
      important atomic relaxations of the topmost surface layer and that sub-surface
      cobalt atoms strongly influence the values of the adsorption energies. The
      calculated Al-O distances are in agreement with those reported in Al2O and Al2O3
      oxides and for oxygen adsorption on Al(111). 

PMID- 23883550
TI  - Assessment of dietary fish consumption in pregnancy: comparing one-, four- and
      thirty-six-item questionnaires.
AB  - OBJECTIVE: Fish consumption influences a number of health outcomes. Few studies
      have directly compared dietary assessment methods to determine the best approach
      to estimating intakes of fish and its component nutrients, including DHA, and
      toxicants, including methylmercury. Our objective was to compare three methods of
      assessing fish intake. DESIGN: We assessed 30 d fish intake using three
      approaches: (i) a single question on total fish consumption; (ii) a brief
      comprehensive FFQ that included four questions about fish; and (iii) a focused
      FFQ with thirty-six questions about different finfish and shellfish. SETTING:
      Obstetrics practices in Boston, MA, USA. SUBJECTS: Fifty-nine pregnant women who
      consumed <=2 monthly fish servings. RESULTS: Estimated intakes of fish, DHA and
      Hg were lowest with the one-question screener and highest with the thirty-six
      item fish questionnaire. Estimated intake of DHA with the thirty-six-item
      questionnaire was 4.4-fold higher (97 v. 22 mg/d), and intake of Hg was 3.8-fold
      higher (1.6 v. 0.42 MUg/d), compared with the one-question screener. Plasma DHA
      concentration was correlated with fish intake assessed with the one-question
      screener (Spearman r = 0.27, P = 0.04), but not with the four-item FFQ (r = 0.08,
      P = 0.54) or the thirty-six-item fish questionnaire (r = 0.01, P = 0.93). In
      contrast, blood and hair Hg concentrations were similarly correlated with fish
      and Hg intakes regardless of the assessment method (r = 0.35 to 0.52).
      CONCLUSIONS: A longer questionnaire provides no advantage over shorter
      questionnaires in ranking intakes of fish, DHA and Hg compared with biomarkers,
      but estimates of absolute intakes can vary by as much as fourfold across methods.

PMID- 23883552
TI  - [Glutamate and malignant gliomas, from epilepsia to biological aggressiveness:
      therapeutic implications].
AB  - In this review article, we describe the unrecognized roles of glutamate and
      glutamate receptors in malignant glioma biology. The neurotransmitter glutamate
      released from malignant glioma cells in the extracellular matrix is responsible
      for seizure induction and at higher concentration neuronal cell death. This
      neuronal cell death will create vacated place for tumor growth. Glutamate also
      stimulates the growth and the migration of glial tumor cells by means of the
      activation of glutamate receptors on glioma cells in a paracrine and autocrine
      manner. The multitude of effects of glutamate in glioma biology supports the
      rationale for pharmacological targeting of glutamate receptors and transporters
      in the adjuvant treatment of malignant gliomas in neurology and neuro-oncology.
      Using the website www.clinicaltrials.gov/ as a reference - a service developed by
      the National Library of Medicine for the National Health Institute in USA - we
      have evoked the few clinical trials completed and currently ongoing with
      therapies targeting the glutamate receptors. 

PMID- 23883553
TI  - Current knowledge and treatment strategies for grade II gliomas.
AB  - World Health Organization grade II gliomas (GIIGs) include diffuse astrocytoma,
      oligodendroglioma, and oligoastrocytoma. GIIG is a malignant brain tumor for
      which the treatment outcome can still be improved. Review of previous clinical
      trials found the following: (1) GIIG increased in size by 3-5 mm per year when
      observed or treated with surgery alone; (2) after pathological diagnosis, the
      survival rate was increased by early aggressive tumor removal at an earlier stage
      compared to observation alone; (3) although the prognosis after total tumor
      removal was significantly better than that after partial tumor removal, half of
      the patients relapsed within 5 years; (4) comparing postoperative early
      radiotherapy (RT) and non-early RT after relapse, early RT prolonged progression
      free survival (PFS) but did not affect overall survival (OS); (5) local RT of 45
      to 64.8 Gy did not impact PFS or OS; (6) in patients with residual tumors, RT
      combined with chemotherapy (procarbazine plus lomustine plus vincristine)
      prolonged PFS compared with RT alone but did not affect OS; and (7) poor
      prognostic factors included astrocytoma, non-total tumor removal, age >=40 years,
      largest tumor diameter >=4-6 cm, tumor crossing the midline, and neurological
      deficit. To improve treatment outcomes, surgery with functional brain mapping or
      intraoperative magnetic resonance imaging or chemoradiotherapy with temozolomide
      is important. In this review, current knowledge regarding GIIG is described and
      treatment strategies are explored. 

PMID- 23883554
TI  - Surgical strategies for nonenhancing slow-growing gliomas with special reference
      to functional reorganization: review with own experience.
AB  - Nonenhancing intrinsic brain tumors have been empirically treated with a strategy
      that has been adopted for World Health Organization (WHO) grade II gliomas (low
      grade gliomas: LGGs), even though small parts of the tumors might have been
      diagnosed as WHO grade III gliomas after surgery. However, the best surgical
      strategy for nonenhancing gliomas, including LGGs, is still debatable. LGGs have
      the following features: slow growth, high possibility of histologically malignant
      transformation, and no clear border between the tumor and adjacent normal brain.
      We retrospectively examined 26 consecutive patients with nonenhancing gliomas who
      were surgically treated at Kanazawa University Hospital between January 2006 and
      May 2012, with special reference to functional reorganization, extent of
      resection (EOR), and functional mapping during awake surgery. These categories
      are closely related with the features of LGG, i.e. functional reorganization due
      to slow-growing nature, EOR with related malignant transformation, and functional
      mapping for delineating the unclear tumor border. Finally, we discuss surgical
      strategies for slow-growing gliomas that are represented by LGGs and nonenhancing
      gliomas. In conclusion, slow-growing gliomas tend to undergo functional
      reorganization, and the functional reorganization affects the presurgical
      evaluation for resectability based on tumor location related to eloquence. In the
      clinical setting, to definitely identify the reorganized functional regions,
      awake surgery is recommended. Therefore, awake surgery could increase the extent
      of the resection of the tumor without deficits, resulting in the delay of
      malignant transformation and increase in overall survival. 

PMID- 23883555
TI  - Updated therapeutic strategy for adult low-grade glioma stratified by resection
      and tumor subtype.
AB  - The importance of surgical resection for patients with supratentorial low-grade
      glioma (LGG) remains controversial. This retrospective study of patients (n =
      153) treated between 2000 to 2010 at a single institution assessed whether
      increasing the extent of resection (EOR) was associated with improved progression
      free survival (PFS) and overall survival (OS). Histological subtypes of World
      Health Organization grade II tumors were as follows: diffuse astrocytoma in 49
      patients (32.0%), oligoastrocytoma in 45 patients (29.4%), and oligodendroglioma
      in 59 patients (38.6%). Median pre- and postoperative tumor volumes and median
      EOR were 29.0 cm(3) (range 0.7-162 cm(3)) and 1.7 cm(3) (range 0-135.7 cm(3)) and
      95%, respectively. Five- and 10-year OS for all LGG patients were 95.1% and
      85.4%, respectively. Eight-year OS for diffuse astrocytoma, oligoastrocytoma, and
      oligodendroglioma were 70.7%, 91.2%, and 98.3%, respectively. Five-year PFS for
      diffuse astrocytoma, oligoastrocytoma, and oligodendroglioma were 42.6%, 71.3%,
      and 62.7%, respectively. Patients were divided into two groups by EOR >=90% and
      <90%, and OS and PFS were analyzed. Both OS and PFS were significantly longer in
      patients with >=90% EOR. Increased EOR resulted in better PFS for diffuse
      astrocytoma but not for oligodendroglioma. Multivariate analysis identified age
      and EOR as parameters significantly associated with OS. The only parameter
      associated with PFS was EOR. Based on these findings, we established updated
      therapeutic strategies for LGG. If surgery resulted in EOR <90%, patients with
      astrocytoma will require second-look surgery, whereas patients with
      oligodendroglioma or oligoastrocytoma, which are sensitive to chemotherapy, will
      be treated with chemotherapy. 

PMID- 23883556
TI  - Summary of 15 years experience of awake surgeries for neuroepithelial tumors in
      tohoku university.
AB  - We retrospectively analyzed 15 years experience of awake surgeries for
      neuroepithelial tumors in Tohoku University. Awake surgeries mostly for language
      mapping were performed for 42 of 681 newly diagnosed cases (6.2%) and 59 of 985
      surgeries including for recurrence (6.0%). When the same histologies and
      locations as cases resected under awake condition are selected from the parent
      population treated by radical resection, awake surgeries were most frequently
      performed for 14 of 55 newly diagnosed cases (25.5%) and 14 of 62 surgeries
      (22.6%) with grade II gliomas. In the results, 8 of 59 surgeries (13.6%) could
      not achieve complete language monitoring until the final stage of tumor
      resection, considered as failed awake surgery. Gross total resection was
      accomplished in 20 of 42 newly diagnosed cases (47.6%) and 32 of 59 surgeries
      (54.2%). Mortality rate was 0%. Late severe deficits were observed in 2 of 42
      newly diagnosed cases (4.8%) and 3 of 59 surgeries (5.1%). Negative language
      mapping cases did not suffer severe deficits in both early and late stages. In
      contrast, high incidence of severe deficits, 3 as early and 2 as late of 8 cases,
      were identified with failed awake surgery. The overall survival of patients
      treated by awake surgery compared favorably with those treated without
      stimulation mapping and with stimulation mapping under general anesthesia. Awake
      surgery may contribute to improve the outcome of gliomas near eloquent areas by
      maximizing the tumor resection and minimizing the surgical morbidity. 

PMID- 23883557
TI  - Risk assessment for venous thromboembolism in patients with neuroepithelial
      tumors: pretreatment score to identify high risk patients.
AB  - The independent risk factors for venous thromboembolism (VTE) were investigated
      in patients with neuroepithelial tumor to establish a risk score for VTE. Our
      prospective study enrolled 395 hospitalized cases with neuroepithelial tumors.
      All cases underwent measurement of serum D-dimer concentration and neurological
      examination on admission. Serum D-dimer concentration was measured on days 1, 3,
      and 7 after surgery and weekly during follow up in patients who underwent
      surgery, and once a week during follow up in patients without surgery. Fourteen
      clinical parameters were evaluated as indicators of VTE, and among them, age,
      body-mass index, chemotherapy, radiation therapy, corticosteroid usage,
      pretreatment serum D-dimer concentration, paresis of the lower extremity (manual
      muscle test: MMT), performance status, and World Health Organization grade of the
      tumor achieved statistical significance. Multivariable logistic regression
      analysis demonstrated age >65 years, corticosteroid usage, paresis of the lower
      extremity, and serum D-dimer concentration over 1.0 mg/dl were independent
      factors. Total risk score was defined as the total of the scores for risk factors
      assigned based on the adjusted odds ratio: pretreatment serum D-dimer
      concentration over 1.0 mg/dl (2 points), and age over 65 years old, paresis of
      the lower extremity of MMT <=2, and corticosteroid usage (1 point each). Rates of
      VTE were 2.0% in the low risk (total score 0 or 1), 14.8% in the intermediate
      risk (total score 2 or 3), and 51.9% in the high risk groups (total score = 4 or
      5). This pretreatment risk score for VTE might be useful to identify patients who
      would benefit from thromboprophylaxis. 

PMID- 23883558
TI  - Clinical characteristics and neuroimaging findings in 12 cases of recurrent
      glioblastoma with communicating hydrocephalus.
AB  - Clinically, recurrent glioblastoma multiforme (GBM) is often associated with
      communicating hydrocephalus. We hypothesized that there are specific magnetic
      resonance (MR) imaging findings at the diagnosis of recurrent GBM that predict
      subsequent hydrocephalus. Various clinical characteristics were investigated
      including outcome and MR imaging findings in 12 patients with recurrent GBM
      followed by hydrocephalus (Hydro group) and 21 patients with recurrent GBM
      without hydrocephalus (Non-hydro group). Patient age and presence of
      communicating hydrocephalus were significantly associated with poor outcome.
      Median survival with recurrent GBM was longer in the Non-hydro group than in the
      Hydro group. Low Karnofsky performance status (KPS) and poor recursive
      partitioning analysis (RPA) class (RPA class 3, 5, 6, or 7) at the diagnosis of
      recurrent GBM were associated with the presence of hydrocephalus. The incidence
      of leptomeningeal dissemination after recurrent GBM was higher in the Hydro group
      than in the Non-hydro group. Evans index and fractional anisotropy value showed
      no difference at the diagnosis of recurrent GBM, but some MR imaging findings
      indicated that lesion attached to the basal cistern and/or ventricle was closely
      associated with subsequent hydrocephalus. We recommend careful monitoring of the
      ventricle size and leptomeningeal dissemination, especially in patients with low
      KPS and/or poor RPA class, if MR imaging indicates that the lesion is attached to
      the basal cistern and/or ventricle at recurrence of GBM. 

PMID- 23883559
TI  - Usefulness of PRESTO magnetic resonance imaging for the differentiation of
      schwannoma and meningioma in the cerebellopontine angle.
AB  - The principles of echo-shifting with a train of observations (PRESTO) magnetic
      resonance (MR) imaging technique employs an MR sequence that sensitively detects
      susceptibility changes in the brain. The effectiveness of PRESTO MR imaging was
      examined for distinguishing between cerebellopontine angle (CPA) schwannomas and
      meningiomas in 24 patients with CPA tumors, 12 with vestibular schwannomas, and
      12 with meningiomas. Histopathological study of surgical specimens showed that 11
      of the 12 schwannomas contained hemosiderin deposits and all had
      microhemorrhages. One meningioma contained hemosiderin deposits and two involved
      microhemorrhages. Abnormal vessel proliferation, and dilated and thrombosed
      vessels were observed in all schwannomas and in 4 meningiomas. In addition to MR
      imaging with all basic sequences, PRESTO MR imaging and computed tomography were
      performed. PRESTO imaging showed significantly more schwannomas (n = 12) than
      meningiomas (n = 2) exhibited intratumoral spotty signal voids which were
      isointense to air in the mastoid air cells (p < 0.001). These spotty signal voids
      were significantly associated with histopathologically demonstrated hemosiderin
      deposits (p < 0.001), microhemorrhages (p < 0.01), and abnormal vessels (p <
      0.04). The visualization of spotty signal voids on PRESTO images is useful to
      distinguish schwannomas from meningiomas. 

PMID- 23883560
TI  - Preoperative evaluation of the petrosal vein with contrast-enhanced PRESTO
      imaging in petroclival meningiomas to establish surgical strategy.
AB  - The present detailed radiological study investigated the relationship between
      petroclival meningiomas and petrosal veins with contrast-enhanced (CE) principles
      of echo-shifting with a train of observations (PRESTO) imaging to assess the
      potential contribution of the findings to the surgical strategy. Fourteen
      patients (13 women and 1 man) with unilateral petroclival meningiomas underwent
      microsurgical resection at Osaka City University Hospital between April 2009 and
      February 2011. Preoperatively, patients were examined using computed tomography
      (CT) and magnetic resonance (MR) imaging, including CE PRESTO imaging, focusing
      on the relationship between the tumor and the petrosal vein, and compared to the
      sensitivity of three-dimensional CT (3D-CT) venography or conventional MR
      imaging, including CE MR venography and constructive interference in steady-state
      (CISS) MR imaging. In 11 of 14 cases, we could identify the petrosal veins with
      intraoperative findings. In 10 of these 14 cases, the anatomical relationship
      between the tumor and the petrosal vein was detected preoperatively with CE
      PRESTO imaging, compared to 5 of 14 cases with 3D-CT venography, 5 of 14 cases
      with CE MR venography, and only 4 of 14 cases using CISS MR imaging. CE PRESTO
      imaging compares favorably to other approaches. There was no venous complication
      related to the surgery in any of the cases. CE PRESTO imaging is a non-invasive
      and useful method to assess the status of the petrosal vein in patients with
      petroclival meningiomas. 

PMID- 23883561
TI  - Detection of tumor progression by signal intensity increase on fluid-attenuated
      inversion recovery magnetic resonance images in the resection cavity of high
      grade gliomas.
AB  - Increased signal intensity (SI) on fluid-attenuated inversion recovery (FLAIR)
      magnetic resonance (MR) images in the resection cavity is sometimes observed
      after partial resection of gliomas. SI in the resection cavity of 44 high-grade
      gliomas was retrospectively investigated. Twelve of 35 patients with progressive
      disease (PD) showed SI increase in the resection cavity, and SI increase preceded
      PD in 6 of these 12 patients. None of nine patients without PD showed SI increase
      during the follow-up period. The analysis of SI on FLAIR images in the resection
      cavity had a specificity of 100% and a sensitivity of 34%. Higher sensitivity was
      found in grade IV tumors than in grade III tumors. SI increase is thus considered
      as a potent highly specific hallmark for subsequent or coincident tumor
      progression, which is clinically useful since MR imaging is easily performed
      during routine clinical examinations. 

PMID- 23883562
TI  - Use of high-field intraoperative magnetic resonance imaging during endoscopic
      transsphenoidal surgery for functioning pituitary microadenomas and small
      adenomas located in the intrasellar region.
AB  - The usefulness of 1.5-T high-field intraoperative magnetic resonance (iMR)
      imaging during transsphenoidal surgery for functioning pituitary adenomas was
      retrospectively evaluated based on long-term endocrine remission from the records
      of 14 patients who underwent transsphenoidal surgery with iMR imaging for
      functioning pituitary microadenomas and small adenomas located in the intrasellar
      region. The maximum tumor diameter was 9.3 +/- 2.6 mm. Patients were diagnosed
      with acromegaly (n = 7), prolactinoma (n = 4), and Cushing's disease (n = 3). If
      iMR imaging detected tumor remnants after resection, the resection cavity was
      reexamined and further resection was performed. Postoperative endocrine follow-up
      period was mean 33.7 +/- 13.3 months. Tumor remnants were detected after the
      first resection in seven patients. Further resection was performed in five of
      these patients, and three achieved long-term endocrine remission. As a result,
      the overall long-term endocrine remission rate was 78.5% (11/14), instead of the
      57.1% (8/14) that would be expected if iMR imaging had not been performed. Long
      term endocrine remission had a tendency to be associated with the absence of
      tumor remnants on the final iMR images, but this was not significant (p = 0.09).
      Long-term endocrine remission was associated with presence of tumor remnants in
      the cavernous sinus on the final iMR images (p = 0.03). High-field iMR imaging is
      useful for depicting tumor remnants after resection, and increased the long-term
      endocrine remission rate for patients with functioning pituitary microadenomas
      and small adenomas. 

PMID- 23883564
TI  - The migration process as a stress factor in pregnant immigrant women in Spain.
AB  - Spain has seen a significant increase of the immigrant population in the past two
      decades. There are 5.6 million registered immigrants in this country, and 63% of
      them range in age between 16 and 41 years; 47% of the immigrant population are
      women. This situation requires additional health care, particularly as it
      pertains to the sexual and reproductive health of female immigrants. The
      objective of our study was to determine if there were differences between women
      of Spanish origin and immigrant women in terms of obstetric outcomes (obstetric
      history, gestational age at end of gestation, and at delivery) and various
      psychological variables during the immediate postpartum period. This was a cross
      sectional study-we evaluated 30 women of Spanish origin and 30 immigrant women
      during the immediate postpartum period. During the 4 months after delivery, we
      proceeded to gather perinatal data for the study participants from their health
      records, partograms, and nursing assessment notes. Additionally, and following
      the immediate postpartum period, participants filled out the Stress Perception
      and Stress Vulnerability Questionnaires, as well as the Optimism Scale. Immigrant
      women have greater perception of stress (p = .00) and vulnerability to stress (p
      = .001) than do Spanish women. However, no group differences were found in
      obstetric variables. 

PMID- 23883565
TI  - The Patient Satisfaction Questionnaire Short Form (PSQ-18) as an adaptable,
      reliable, and validated tool for use in various settings.

PMID- 23883566
TI  - Post-radioembolization yttrium-90 PET/CT - part 1: diagnostic reporting.
AB  - BACKGROUND: Yttrium-90 (90Y) positron emission tomography with integrated
      computed tomography (PET/CT) represents a technological leap from 90Y
      bremsstrahlung single-photon emission computed tomography with integrated
      computed tomography (SPECT/CT) by coincidence imaging of low abundance internal
      pair production. Encouraged by favorable early experiences, we implemented post
      radioembolization 90Y PET/CT as an adjunct to 90Y bremsstrahlung SPECT/CT in
      diagnostic reporting. METHODS: This is a retrospective review of all paired 90Y
      PET/CT and 90Y bremsstrahlung SPECT/CT scans over a 1-year period. We compared
      image resolution, ability to confirm technical success, detection of non-target
      activity, and providing conclusive information about 90Y activity within targeted
      tumor vascular thrombosis. 90Y resin microspheres were used. 90Y PET/CT was
      performed on a conventional time-of-flight lutetium-yttrium-oxyorthosilicate
      scanner with minor modifications to acquisition and reconstruction parameters.
      Specific findings on 90Y PET/CT were corroborated by 90Y bremsstrahlung SPECT/CT,
      99mTc macroaggregated albumin SPECT/CT, follow-up diagnostic imaging or review of
      clinical records. RESULTS: Diagnostic reporting recommendations were developed
      from our collective experience across 44 paired scans. Emphasis on the continuity
      of care improved overall diagnostic accuracy and reporting confidence of the
      operator. With proper technique, the presence of background noise did not pose a
      problem for diagnostic reporting. A counter-intuitive but effective technique of
      detecting non-target activity is proposed, based on the pattern of activity and
      its relation to underlying anatomy, instead of its visual intensity. In a sub
      analysis of 23 patients with a median follow-up of 5.4 months, 90Y PET/CT
      consistently outperformed 90Y bremsstrahlung SPECT/CT in all aspects of
      qualitative analysis, including assessment for non-target activity and tumor
      vascular thrombosis. Parts of viscera closely adjacent to the liver remain
      challenging for non-target activity detection, compounded by a tendency for mis
      registration. CONCLUSIONS: Adherence to proper diagnostic reporting technique and
      emphasis on continuity of care are vital to the clinical utility of post
      radioembolization 90Y PET/CT. 90Y PET/CT is superior to 90Y bremsstrahlung
      SPECT/CT for the assessment of target and non-target activity.

PMID- 23883567
TI  - Neurobiological effects of the green tea constituent theanine and its potential
      role in the treatment of psychiatric and neurodegenerative disorders.
AB  - Theanine (n-ethylglutamic acid), a non-proteinaceous amino acid component of
      green and black teas, has received growing attention in recent years due to its
      reported effects on the central nervous system. It readily crosses the blood
      brain barrier where it exerts a variety of neurophysiological and pharmacological
      effects. Its most well-documented effect has been its apparent anxiolytic and
      calming effect due to its up-regulation of inhibitory neurotransmitters and
      possible modulation of serotonin and dopamine in selected areas. It has also
      recently been shown to increase levels of brain-derived neurotrophic factor. An
      increasing number of studies demonstrate a neuroprotective effects following
      cerebral infarct and injury, although the exact molecular mechanisms remain to be
      fully elucidated. Theanine also elicits improvements in cognitive function
      including learning and memory, in human and animal studies, possibly via a
      decrease in NMDA-dependent CA1 long-term potentiation (LTP) and increase in NMDA
      independent CA1-LTP. Furthermore, theanine administration elicits selective
      changes in alpha brain wave activity with concomitant increases in selective
      attention during the execution of mental tasks. Emerging studies also demonstrate
      a promising role for theanine in augmentation therapy for schizophrenia, while
      animal models of depression report positive improvements following theanine
      administration. A handful of studies are beginning to examine a putative role in
      attention deficit hyperactivity disorder, and theoretical extrapolations to a
      therapeutic role for theanine in other psychiatric disorders such as anxiety
      disorders, panic disorder, obsessive compulsive disorder (OCD), and bipolar
      disorder are discussed. 

PMID- 23883568
TI  - A fiber-based implantable multi-optrode array with contiguous optical and
      electrical sites.
AB  - OBJECTIVE: Although various kinds of optrodes are designed to deliver light and
      sense electrophysiological responses, few have a tightly closed optical
      delivering site or electrical recording site. The large space between them often
      blurs the stimulation location and light intensity threshold. APPROACH: Based on
      an optical fiber, we develop an optrode structure which has a coniform tip where
      the light exit point and gold-based electrode site are located. The optrode is
      fabricated by integrating a metal membrane electrode on the outside of a tapered
      fiber. Half of the cone-shape tip is covered by a layer of gold membrane to form
      the electrode. A commercial fiber connector, mechanical transfer (MT) module, is
      chosen to assemble the multi-optrode array (MOA). The MT connector acts as both
      the holder of the optrode array and an aligning part to connect the MOA with the
      light source. MAIN RESULTS: We fabricated a pluggable MOA weighing only 0.2 g.
      The scanning electron microscope images showed a tight cover of the metal layer
      on the optrode tip with an exposure area of 1500 um(2). The electrochemical
      impedance of the optrode at 1 kHz was 100 kOmega on average and the light
      emission intensity reached 13 mW. The optical modulating and electrophysiological
      recording ability of the MOA was validated by monitoring the response of cells in
      a ChR2-expressing mouse's cerebral cortex. Neurons that maintained high cluster
      quality (signal-to-noise ratio = 5:1) and coherence in response to trains of 20
      Hz stimulation were monitored. SIGNIFICANCE: The optrode array reduces the
      distance between the optical stimulating sites and electrophysiological sites
      dramatically and can supply multiple channels to guide different lights
      simultaneously. This optrode with its novel structure may lead to a different
      kind of optical neural control prosthetic device, opening up a new option for
      neural modulation in the brain.

PMID- 23883569
TI  - Molecular Cytogenetics: the first impact factor (2.36).

PMID- 23883570
TI  - Long-term effect of dietary fibre intake on glycosylated haemoglobin A1c level
      and glycaemic control status among Chinese patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: Dietary fibre has been linked to lower levels of glycosylated
      haemoglobin A1c (HbA1c) among diabetes patients. The present study aimed to
      evaluate the long-term effect of dietary fibre on HbA1c levels among Chinese
      patients with type 2 diabetes mellitus. DESIGN: Two cross-sectional surveys were
      conducted in 2006 and 2011, with the second one being a repeat survey on a sub
      sample from the initial one. In both surveys, an in-person interview was
      conducted to collect information on demographic characteristics and lifestyles
      following a similar protocol. Dietary intake was assessed with a validated FFQ.
      Anthropometric measures and biochemical assays were performed at the interview.
      SETTING: Communities in Pudong New Area of Shanghai, China. SUBJECTS: Chinese
      patients (n 934) with type 2 diabetes mellitus. RESULTS: An inverse association
      was observed between dietary fibre and glycaemic status indicated by HbA1c level
      in both surveys, although it was significant only in the first survey. Among 497
      patients participating in both surveys, dietary fibre intake at the first survey
      was inversely associated with uncontrolled glycaemic status at the second survey,
      with adjusted odds ratios across the tertiles of intake being 1.00, 0.72 (95 % CI
      0.43, 1.21) and 0.58 (95 % CI 0.34, 0.99; P trend = 0.048). The change in fibre
      intake was slightly associated with glycaemic status, with each increase in
      tertile scores of intake linked to a 0.138 % (beta = -0.138; 95 % CI -0.002,
      0.278) decrease in HbA1c value and a 19 % (OR = 0.81; 95 % CI 0.65, 1.02) reduced
      risk of uncontrolled glycaemic status at the second survey. CONCLUSIONS: Dietary
      fibre may have a long-term beneficial effect on HbA1c level among Chinese
      diabetes patients.

PMID- 23883571
TI  - Whole body protein kinetics during hypocaloric and normocaloric feeding in
      critically ill patients.
AB  - INTRODUCTION: Optimal feeding of critically ill patients in the ICU is
      controversial. Existing guidelines rest on rather weak evidence. Whole body
      protein kinetics may be an attractive technique for assessing optimal protein
      intake. In this study, critically ill patients were investigated during
      hypocaloric and normocaloric IV nutrition. METHODS: Neurosurgical patients on
      mechanical ventilation (n = 16) were studied during a 48-hour period. In random
      order 50% and 100% of measured energy expenditure was given as IV nutrition
      during 24 hours, corresponding to hypocaloric and normocaloric nutrition,
      respectively. At the end of each period, whole body protein turnover was measured
      using d5-phenylalanine and 13C-leucine tracers. RESULTS: The phenylalanine tracer
      indicated that whole-body protein synthesis was lower during hypocaloric feeding,
      while whole-body protein degradation and amino acid oxidation were unaltered,
      which resulted in a more negative protein balance, namely -1.9 +/- 2.1 versus 
      0.7 +/- 1.3 mg phenylalanine/kg/h (P = 0.014). The leucine tracer indicated that
      whole body protein synthesis and degradation and amino acid oxidation were
      unaltered, but the protein balance was negative during hypocaloric feeding,
      namely -0.3 +/- 0.5 versus 0.6 +/- 0.5 mg leucine/kg/h (P < 0.001). CONCLUSION:
      In the patient group studied, hypocaloric feeding was associated with a more
      negative protein balance, but the amino acid oxidation was not different. The
      protein kinetics measurements and the study's investigational protocol were
      useful for assessing the efficacy of nutrition support on protein metabolism in
      critically ill patients.

PMID- 23883572
TI  - Sexual conflict and the function of genitalic claws in guppies (Poecilia
      reticulata).
AB  - Poeciliid fish, freshwater fish with internal fertilization, are known for the
      diversity of structures on the male intromittent organ, the gonopodium. Prominent
      among these, in some species, is a pair of claws at its tip. We conducted a
      manipulative study of these claws in the guppy, Poecilia reticulata, to determine
      if these aid in transferring sperm to resistant females. We compared the sperm
      transfer rates of clawed versus surgically declawed males attempting to mate with
      either receptive or unreceptive (i.e. resistant) females. Our analyses
      demonstrate that the gonopodial claws function to increase sperm transfer to
      unreceptive females during uncooperative matings but not during receptive
      matings. Up to threefold more sperm were transferred to unreceptive females by
      clawed than declawed males. These data suggest that the claw is a sexually
      antagonistic trait, functioning to aid in transferring sperm to resistant
      females, and implicate sexual conflict as a selective force in the
      diversification of the gonopodium in the Poeciliidae. 

PMID- 23883573
TI  - Differences in offspring size predict the direction of isolation asymmetry
      between populations of a placental fish.
AB  - Crosses between populations or species often display an asymmetry in the fitness
      of reciprocal F1 hybrids. This pattern, referred to as isolation asymmetry or
      Darwin's Corollary to Haldane's Rule, has been observed in taxa from plants to
      vertebrates, yet we still know little about which factors determine its magnitude
      and direction. Here, we show that differences in offspring size predict the
      direction of isolation asymmetry observed in crosses between populations of a
      placental fish, Heterandria formosa. In crosses between populations with
      differences in offspring size, high rates of hybrid inviability occur only when
      the mother is from a population characterized by small offspring. Crosses between
      populations that display similarly sized offspring, whether large or small, do
      not result in high levels of hybrid inviability in either direction. We suggest
      this asymmetric pattern of reproductive isolation is due to a disruption of
      parent-offspring coadaptation that emerges from selection for differently sized
      offspring in different populations. 

PMID- 23883574
TI  - Real-time characterization of the molecular epidemiology of an influenza
      pandemic.
AB  - Early characterization of the epidemiology and evolution of a pandemic is
      essential for determining the most appropriate interventions. During the 2009
      H1N1 influenza A pandemic, public databases facilitated widespread sharing of
      genetic sequence data from the outset. We use Bayesian phylogenetics to simulate
      real-time estimates of the evolutionary rate, date of emergence and intrinsic
      growth rate (r0) of the pandemic from whole-genome sequences. We investigate the
      effects of temporal range of sampling and dataset size on the precision and
      accuracy of parameter estimation. Parameters can be accurately estimated as early
      as two months after the first reported case, from 100 genomes and the choice of
      growth model is important for accurate estimation of r0. This demonstrates the
      utility of simple coalescent models to rapidly inform intervention strategies
      during a pandemic. 

PMID- 23883575
TI  - Nestling telomere length does not predict longevity, but covaries with adult body
      size in wild barn swallows.
AB  - Telomere length and dynamics are increasingly scrutinized as ultimate
      determinants of performance, including age-dependent mortality and fecundity. Few
      studies have investigated longevity in relation to telomere length (TL) in the
      wild and none has analysed longevity in relation to TL soon after hatching,
      despite the fact that telomere shortening may mostly occur early in life. We show
      that TL in nestling barn swallows (Hirundo rustica) in the wild does not predict
      longevity. However, TL positively covaries with body size, suggesting that
      individuals with large TL can afford to grow larger without paying the cost of
      reduced TL, and/or that benign rearing conditions ensure both large body size and
      low rates of telomere shortening. Overall, our study hints at a role of TL in
      developmental processes, but also indicates a need for further analyses to assess
      the expectation that TL in young individuals predicts longevity in the wild. 

PMID- 23883576
TI  - Reciprocal feeding facilitation between above- and below-ground herbivores.
AB  - Interspecific interactions between insect herbivores predominantly involve
      asymmetric competition. By contrast, facilitation, whereby herbivory by one
      insect benefits another via induced plant susceptibility, is uncommon. Positive
      reciprocal interactions between insect herbivores are even rarer. Here, we reveal
      a novel case of reciprocal feeding facilitation between above-ground aphids
      (Amphorophora idaei) and root-feeding vine weevil larvae (Otiorhynchus sulcatus),
      attacking red raspberry (Rubus idaeus). Using two raspberry cultivars with
      varying resistance to these herbivores, we further demonstrate that feeding
      facilitation occurred regardless of host plant resistance. This positive
      reciprocal interaction operates via an, as yet, unreported mechanism.
      Specifically, the aphid induces compensatory growth, possibly as a prelude to
      greater resistance/tolerance, whereas the root herbivore causes the plant to
      abandon this strategy. Both herbivores may ultimately benefit from this
      facilitative interaction. 

PMID- 23883577
TI  - Developing ultraviolet illumination of gillnets as a method to reduce sea turtle
      bycatch.
AB  - Fisheries bycatch of marine animals has been linked to population declines of
      multiple species, including many sea turtles. Altering the visual cues associated
      with fishing gear may reduce sea turtle bycatch. We examined the effectiveness of
      illuminating gillnets with ultraviolet (UV) light-emitting diodes for reducing
      green sea turtle (Chelonia mydas) interactions. We found that the mean sea turtle
      capture rate was reduced by 39.7% in UV-illuminated nets compared with nets
      without illumination. In collaboration with commercial fishermen, we tested UV
      net illumination in a bottom-set gillnet fishery in Baja California, Mexico. We
      did not find any difference in overall target fish catch rate or market value
      between net types. These findings suggest that UV net illumination may have
      applications in coastal and pelagic gillnet fisheries to reduce sea turtle
      bycatch. 

PMID- 23883578
TI  - Cheetah do not abandon hunts because they overheat.
AB  - Hunting cheetah reportedly store metabolic heat during the chase and abandon
      chases because they overheat. Using biologging to remotely measure the body
      temperature (every minute) and locomotor activity (every 5 min) of four free
      living cheetah, hunting spontaneously, we found that cheetah abandoned hunts, but
      not because they overheated. Body temperature averaged 38.4 degrees C when the
      chase was terminated. Storage of metabolic heat did not compromise hunts. The
      increase in body temperature following a successful hunt was double that of an
      unsuccessful hunt (1.3 degrees C +/- 0.2 degrees C versus 0.5 degrees C +/- 0.1
      degrees C), even though the level of activity during the hunts was similar. We
      propose that the increase in body temperature following a successful hunt is a
      stress hyperthermia, rather than an exercise-induced hyperthermia. 

PMID- 23883579
TI  - A new hero emerges: another exceptional mammalian spine and its potential
      adaptive significance.
AB  - The hero shrew's (Scutisorex somereni) massive interlocking lumbar vertebrae
      represent the most extreme modification of the vertebral column known in mammals.
      No intermediate form of this remarkable morphology is known, nor is there any
      convincing theory to explain its functional significance. We document a new
      species in the heretofore monotypic genus Scutisorex; the new species possesses
      cranial and vertebral features representing intermediate character states between
      S. somereni and other shrews. Phylogenetic analyses of DNA sequences support a
      sister relationship between the new species and S. somereni. While the function
      of the unusual spine in Scutisorex is unknown, it gives these small animals
      incredible vertebral strength. Based on field observations, we hypothesize that
      the unique vertebral column is an adaptation allowing these shrews to lever heavy
      or compressive objects to access concentrated food resources inaccessible to
      other animals. 

PMID- 23883580
TI  - Effects of Oxidized Konjac glucomannan (OKGM) on growth and immune function of
      Schizothorax prenanti.
AB  - Schizothorax prenanti is an important existemic commercial fish in River Yangtze.
      OKGM (Oxidized Konjac glucomannan) is a kind of polysaccharide oxidative degraded
      from KGM. Added 500, 1000, 2000, 4000, 8000 mg/kg OKGM into the diets of S.
      prenanti. After 60 days feeding trial, WGR (weight gain rate), SGR (specific
      growth rate), PER (protein efficiency ratio) of groups fed the diet with 8000
      mg/kg OKGM was all significantly (P < 0.05) higher; FCR (feed conversion ratio)
      was significantly lower than the control group whose diet have no OKGM.
      Hepatopancreas index, spleen index of group 6 whose feed added 8000 mg/kg OKGM
      were significantly higher and gallbladder index was significantly lower than the
      control group. Erythrocyte number, leukocyte number of group 5, 6 whose feed
      added 4000, 8000 mg/kg OKGM were excellent significantly (P < 0.01) more than the
      control group. At the same time, Erythrocyte phagocytic rate, erythrocyte
      phagocytic index, neutrophilic granulocyte phagocytic rate, neutrophilic
      granulocyte phagocytic index of all the groups whose diet added OKGM were
      significantly higher than the control group. Content of IgM, C3 of group 4 whose
      feed added 2000 mg/kg OKGM were significantly more than the control group. As for
      activity of CAT, group 6 was significantly higher than the control group. When
      compared activity of SOD, group 6 was significantly higher than group 1, 2, 3.
      Accordingly, activity of GSH-Px of group 3, 4, 5, 6 were significantly higher
      than the control group. On the contrary, content of MDA, group 3, 4, 5, 6 whose
      feed added 1000-8000 mg/kg OKGM was excellent significantly lower than the
      control group. After injected Aeromonas hydrophila 21 days, only group 6 whose
      feed added 8000 mg/kg OKGM survived excellent significantly more than the control
      group. So we can draw a conclusion of that added OKGM in the diets of S.
      prenanti, not only promoted growth, but also improved immune function, and the
      best dose was 8000 mg/kg in this experiment. 

PMID- 23883581
TI  - Human platelets generate phospholipid-esterified prostaglandins via
      cyclooxygenase-1 that are inhibited by low dose aspirin supplementation.
AB  - Oxidized phospholipids (oxPLs) generated nonenzymatically display pleiotropic
      biological actions in inflammation. Their generation by cellular cyclooxygenases
      (COXs) is currently unknown. To determine whether platelets generate
      prostaglandin (PG)-containing oxPLs, then characterize their structures and
      mechanisms of formation, we applied precursor scanning-tandem mass spectrometry
      to lipid extracts of agonist-activated human platelets. Thrombin, collagen, or
      ionophore activation stimulated generation of families of PGs comprising PGE2 and
      D2 attached to four phosphatidylethanolamine (PE) phospholipids (16:0p/, 18:1p/,
      18:0p/, and 18:0a/). They formed within 2 to 5 min of activation in a calcium,
      phospholipase C, p38 MAP kinases, MEK1, cPLA2, and src tyrosine kinase-dependent
      manner (28.1 +/- 2.3 pg/2 * 108 platelets). Unlike free PGs, they remained cell
      associated, suggesting an autocrine mode of action. Their generation was
      inhibited by in vivo aspirin supplementation (75 mg/day) or in vitro COX-1
      blockade. Inhibitors of fatty acyl reesterification blocked generation
      significantly, while purified COX-1 was unable to directly oxidize PE in vitro.
      This indicates that they form in platelets via rapid esterification of COX-1
      derived PGE2/D2 into PE. In summary, COX-1 in human platelets acutely mediates
      membrane phospholipid oxidation via formation of PG-esterified PLs in response to
      pathophysiological agonists.

PMID- 23883582
TI  - Volumetric determination of apolipoprotein stoichiometry of circulating HDL
      subspecies.
AB  - Although HDL is inversely correlated with coronary heart disease, elevated HDL
      cholesterol is not always protective. Additionally, HDL has biological functions
      that transcend any antiatherogenic role: shotgun proteomics show that HDL
      particles contain 84 proteins (latest count), many correlating with antioxidant
      and anti-inflammatory properties of HDL. ApoA-I has been suggested to serve as a
      platform for the assembly of these protein components on HDL with specific
      functions - the HDL proteome. However, the stoichiometry of apoA-I in HDL
      subspecies is poorly understood. Here we use a combination of immunoaffinity
      chromatography data and volumetric analysis to evaluate the size and
      stoichiometry of LpA-I and LpA-I,A-II particles. We conclude that there are three
      major LpA-I subspecies: two major particles, HDL[4] in the HDL3 size range (d =
      85.0 +/- 1.2 A) and HDL[7] in the HDL2 size range (d = 108.5 +/- 3.8 A) with apoA
      I stoichiometries of 3 and 4, respectively, and a small minor particle, HDL[1] (d
      = 73.8 +/- 2.1A) with an apoA-I stoichiometry of 2. Additionally, we conclude
      that the molar ratio of apolipoprotein to surface lipid is significantly higher
      in circulating HDL subspecies than in reconstituted spherical HDL particles,
      presumably reflecting a lack of phospholipid transfer protein in reconstitution
      protocols. 

PMID- 23883584
TI  - Glycolysis inhibition sensitizes non-small cell lung cancer with T790M mutation
      to irreversible EGFR inhibitors via translational suppression of Mcl-1 by AMPK
      activation.
AB  - The secondary EGF receptor (EGFR) T790M is the most common mechanism of
      resistance to reversible EGFR-tyrosine kinase inhibitors (TKI) in patients with
      non-small cell lung cancer (NSCLC) with activating EGFR mutations. Although
      afatinib (BIBW2992), a second-generation irreversible EGFR-TKI, was expected to
      overcome the acquired resistance, it showed limited efficacy in a recent phase
      III clinical study. In this study, we found that the inhibition of glycolysis
      using 2-deoxy-d-glucose (2DG) improves the efficacy of afatinib in H1975 and PC9
      GR NSCLC cells with EGFR T790M. Treatment with the combination of 2DG and
      afatinib induced intracellular ATP depletion in both H1975 and PC9-GR cells,
      resulting in activation of AMP-activated protein kinase (AMPK). AMPK activation
      played a central role in the cytotoxicity of the combined treatment with 2DG and
      afatinib through the inhibition of mTOR. The alteration of the AMPK/mTOR
      signaling pathway by the inhibition of glucose metabolism induced specific
      downregulation of Mcl-1, a member of the antiapoptotic Bcl-2 family, through
      translational control. The enhancement of afatinib sensitivity by 2DG was
      confirmed in the in vivo PC9-GR xenograft model. In conclusion, this study
      examined whether the inhibition of glucose metabolism using 2DG enhances
      sensitivity to afatinib in NSCLC cells with EGFR T790M through the regulation of
      the AMPK/mTOR/Mcl-1 signaling pathway. These data suggest that the combined use
      of an inhibitor of glucose metabolism and afatinib is a potential therapeutic
      strategy for the treatment of patients with acquired resistance to reversible
      EGFR-TKIs due to secondary EGFR T790M.

PMID- 23883583
TI  - N-acetyl lysyltyrosylcysteine amide inhibits myeloperoxidase, a novel tripeptide
      inhibitor.
AB  - Myeloperoxidase (MPO) plays important roles in disease by increasing oxidative
      and nitrosative stress and oxidizing lipoproteins. Here we report N-acetyl
      lysyltyrosylcysteine amide (KYC) is an effective inhibitor of MPO activity. We
      show KYC inhibits MPO-mediated hypochlorous acid (HOCl) formation and
      nitration/oxidation of LDL. Disulfide is the major product of MPO-mediated KYC
      oxidation. KYC (<=4,000 MUM) does not induce cytotoxicity in bovine aortic
      endothelial cells (BAECs). KYC inhibits HOCl generation by phorbol myristate
      acetate (PMA)-stimulated neutrophils and human promyelocytic leukemia (HL-60)
      cells but not superoxide generation by PMA-stimulated HL-60 cells. KYC inhibits
      MPO-mediated HOCl formation in BAEC culture and protects BAECs from MPO-induced
      injury. KYC inhibits MPO-mediated lipid peroxidation of LDL whereas tyrosine
      (Tyr) and tryptophan (Trp) enhance oxidation. KYC is unique as its isomers do not
      inhibit MPO activity, or are much less effective. Ultraviolet-visible spectral
      studies indicate KYC binds to the active site of MPO and reacts with compounds I
      and II. Docking studies show the Tyr of KYC rests just above the heme of MPO.
      Interestingly, KYC increases MPO-dependent H2O2 consumption. These data indicate
      KYC is a novel and specific inhibitor of MPO activity that is nontoxic to
      endothelial cell cultures. Accordingly, KYC may be useful for treating MPO
      mediated vascular disease.

PMID- 23883585
TI  - Catalase abrogates beta-lapachone-induced PARP1 hyperactivation-directed
      programmed necrosis in NQO1-positive breast cancers.
AB  - Improving patient outcome by personalized therapy involves a thorough
      understanding of an agent's mechanism of action. beta-Lapachone (clinical forms,
      Arq501/Arq761) has been developed to exploit dramatic cancer-specific elevations
      in the phase II detoxifying enzyme NAD(P)H:quinone oxidoreductase (NQO1). NQO1 is
      dramatically elevated in solid cancers, including primary and metastatic [e.g.,
      triple-negative (ER-, PR-, Her2/Neu-)] breast cancers. To define cellular factors
      that influence the efficacy of beta-lapachone using knowledge of its mechanism of
      action, we confirmed that NQO1 was required for lethality and mediated a futile
      redox cycle where ~120 moles of superoxide were formed per mole of beta-lapachone
      in 2 minutes. beta-Lapachone induced reactive oxygen species (ROS), stimulated
      DNA single-strand break-dependent poly(ADP-ribose) polymerase-1 (PARP1)
      hyperactivation, caused dramatic loss of essential nucleotides (NAD(+)/ATP), and
      elicited programmed necrosis in breast cancer cells. Although PARP1
      hyperactivation and NQO1 expression were major determinants of beta-lapachone
      induced lethality, alterations in catalase expression, including treatment with
      exogenous enzyme, caused marked cytoprotection. Thus, catalase is an important
      resistance factor and highlights H2O2 as an obligate ROS for cell death from this
      agent. Exogenous superoxide dismutase enhanced catalase-induced cytoprotection.
      beta-Lapachone-induced cell death included apoptosis-inducing factor (AIF)
      translocation from mitochondria to nuclei, TUNEL+ staining, atypical PARP1
      cleavage, and glyceraldehyde 3-phosphate dehydrogenase S-nitrosylation, which
      were abrogated by catalase. We predict that the ratio of NQO1:catalase activities
      in breast cancer versus associated normal tissue are likely to be the major
      determinants affecting the therapeutic window of beta-lapachone and other NQO1
      bioactivatable drugs.

PMID- 23883586
TI  - Synthetic lethal targeting of PTEN-deficient cancer cells using selective
      disruption of polynucleotide kinase/phosphatase.
AB  - A recent screen of 6,961 siRNAs to discover possible synthetic lethal partners of
      the DNA repair protein polynucleotide kinase/phosphatase (PNKP) led to the
      identification of the potent tumor suppressor phosphatase and tensin homolog
      deleted on chromosome 10 (PTEN). Here, we have confirmed the PNKP/PTEN synthetic
      lethal partnership in a variety of different cell lines including the PC3
      prostate cancer cell line, which is naturally deficient in PTEN. We provide
      evidence that codepletion of PTEN and PNKP induces apoptosis. In HCT116 colon
      cancer cells, the loss of PTEN is accompanied by an increased background level of
      DNA double-strand breaks, which accumulate in the presence of an inhibitor of
      PNKP DNA 3'-phosphatase activity. Complementation of PC3 cells with several well
      characterized mutated PTEN cDNAs indicated that the critical function of PTEN
      required to prevent toxicity induced by an inhibitor of PNKP is most likely
      associated with its cytoplasmic lipid phosphatase activity. Finally, we show that
      modest inhibition of PNKP in a PTEN knockout background enhances cellular
      radiosensitivity, suggesting that such a "synthetic sickness" approach involving
      the combination of PNKP inhibition with radiotherapy may be applicable to PTEN
      deficient tumors.

PMID- 23883588
TI  - Pioneering and fundamental achievements on the development of positron emission
      tomography (PET) in oncology.
AB  - Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG), a
      glucose analog, is widely used throughout the world as an indispensable imaging
      modality for the management of cancer treatment. This article reviews the
      pioneering achievements of PET in oncology with a focus on the development of PET
      that occurred from 1980 through the early-1990s. (18)F-FDG was first applied for
      imaging of animal tumors in 1980 and for brain tumor imaging clinically in 1982.
      (18)F-FDG enabled to visualize liver metastasis as clear positive image that
      could not be obtained by conventional nuclear imaging. Subsequently, (18)F-FDG
      was used for imaging various cancers, such as lung, pancreas, colorectal and
      hepatoma. (11)C-L-methionine ((11)C-MET) that reflects amino acid transport of
      cancers has an advantage that its uptake is lower in the brain and inflammatory
      tissue compared to (18)F-FDG, and was first applied for imaging lung cancer and
      brain tumor. (18)F-FDG and (11)C-MET were proved to be sensitive tracers that can
      be used to objectively evaluate the effectiveness of cancer treatment. The
      diagnostic accuracy of PET, which is critical in clinical practice, was evaluated
      for the differential diagnosis of malignant and benign lung nodules using (18)F
      FDG or (11)C-MET. In addition to (18)F-FDG and (11)C-MET, many
      radiopharmaceuticals were developed, such as (18)F-labled thymidine analogs for
      evaluating proliferative activity, (18)F-fluoromisonidazole for imaging of
      hypoxia, and (18)F-fluorodeoxygalactose for evaluating liver-specific galactose
      metabolism and for imaging of hepatoma that retains galactose metabolic activity.
      These early efforts and achievements have greatly contributed to the development
      and clinical application of (18)F-FDG PET in oncology. 

PMID- 23883587
TI  - Ethnic and religious discrimination: the multifaceted role of religiosity and
      collective self-esteem.
AB  - This study analyses the roles of collective self-esteem and religiosity in the
      relationship between discrimination and psychological distress among a sample of
      432 recent immigrants from Haiti and Arab countries living in Montreal, Quebec.
      Collective self-esteem (CSE), religiosity, discriminatory experiences, and
      psychological symptoms of depression and anxiety were assessed. Regression
      analyses revealed direct negative effects of discrimination, CSE, and religiosity
      on psychological distress for the entire sample. CSE, however, also appeared to
      moderate the effects of discrimination on psychological distress. Participants
      with higher CSE reported lower levels of anxiety and depression as a result of
      discrimination compared to those who expressed lower CSE levels. The results
      suggest that the relationship between CSE, discrimination, and psychological
      distress must be reexamined in light of recent sociopolitical changes and the
      upsurge in ethnic and religious tensions following the war on terror. 

PMID- 23883589
TI  - Low incidence of sight-threatening retinopathy of prematurity in infants born
      before 28 weeks gestation at a neonatal intensive care unit in Japan.
AB  - Improvement in neonatal care has led to increased survival rates of very
      premature infants. Accordingly, there are now more extremely preterm infants who
      are at risk of developing retinopathy of prematurity (ROP). ROP is a disorder of
      low birth-weight preterm infants and may lead to blindness. However, the
      prevalence of ROP varies globally, depending on different neonatal and ophthalmic
      care. Therefore, we studied the incidence and progression of ROP in extremely
      preterm infants in Japan. In addition, we investigated the characteristics and
      the clinical courses of the infants who progressed to sight-threatening ROP. A
      total of 3,154 infants were born at the Japanese Red Cross Sendai Hospital
      between 2009 and 2011, including 53 live-born infants born before 28 weeks'
      gestation. Two extremely preterm infants died before the first ROP examination.
      Among the survived 51 infants (the birth-weight ranged from 309 to 1,354 g, mean
      779 g), 36 infants (70.6%) developed ROP: 18 infants with mild ROP and 18 infants
      with severe ROP. Eight out of the 51 infants (15.7%) underwent laser treatment.
      None of the infants born at older than 27 weeks 0 day of gestation required any
      treatment for ROP. In conclusion, most of extremely preterm infants develop some
      degree of ROP. However, in the majority of these infants the ROP never progressed
      beyond mild disease and resolved spontaneously without treatment. Sight
      threatening ROP was rare. The present study clarifies the natural history of ROP
      in extremely preterm infants with active perinatal care. 

PMID- 23883590
TI  - Plasma-enhanced chemical vapor deposition of ortho-carborane: structural insights
      and interaction with Cu overlayers.
AB  - X-ray and ultraviolet photoelectron spectroscopy (XPS, UPS) are used to
      investigate the chemical and electronic structure of boron carbide films
      deposited from ortho-carborane precursors using plasma-enhanced chemical vapor
      deposition (PECVD), and the reactivity of PECVD films toward sputter-deposited Cu
      overlayers. The XPS data provide clear evidence of enhanced ortho-carborane
      reactivity with the substrate, and of extra-icosahedral boron and carbon species;
      these results differ from results for films formed by condensation and electron
      beam induced cross-linking of ortho-carborane (EBIC films). The UPS data show
      that the valence band maximum for PECVD films is ~1.5 eV closer to the Fermi
      level than for EBIC films. The XPS data also indicate that PECVD films are
      resistant to thermally-stimulated diffusion of Cu at temperatures up to 1000 K in
      UHV, in direct contrast to recently reported results, but important for
      applications in neutron detection and in microelectronics.

PMID- 23883592
TI  - [The importance of individual beliefs about cancer treatments for therapeutic
      decisions].
AB  - Interest for representations about cancer treatments and their side effects is
      increasing because their central role has been proved in how patients cope with
      illness and symptoms and how they react emotionally. Through a synthesis of the
      literature, this paper has two objectives: firstly, to clarify the current state
      of knowledge in this field, and secondly to point out the manner that bringing
      out these individual representations during oncological consultations contributes
      to preventing difficulties and treatment discontinuation and facilitates medical
      decision processing. 

PMID- 23883591
TI  - Natriuretic peptide receptors regulate cytoprotective effects in a human ex vivo
      3D/bioreactor model.
AB  - INTRODUCTION: The present study examined the effect of C-type natriuretic peptide
      (CNP) and biomechanical signals on anabolic and catabolic activities in
      chondrocyte/agarose constructs. METHODS: Natriuretic peptide (Npr) 2 and 3
      expression were compared in non-diseased (grade 0/1) and diseased (grade IV)
      human cartilage by immunofluoresence microscopy and western blotting. In separate
      experiments, constructs were cultured under free-swelling conditions or subjected
      to dynamic compression with CNP, interleukin-1beta (IL-1beta), the Npr2
      antagonist P19 or the Npr3 agonist cANF4-23. Nitric oxide (NO) production,
      prostaglandin E2 (PGE2) release, glycosaminoglycan (GAG) synthesis and CNP
      concentration were quantified using biochemical assays. Gene expression of Npr2,
      Npr3, CNP, aggrecan and collagen type II were assessed by real-time qPCR. Two-way
      ANOVA and a post hoc Bonferroni-corrected t-test were used to analyse the data.
      RESULTS: The present study demonstrates increased expression of natriuretic
      peptide receptors in diseased or older cartilage (age 70) when compared to non
      diseased tissue (age 60) which showed minimal expression. There was strong
      parallelism in the actions of CNP on cGMP induction resulting in enhanced GAG
      synthesis and reduction of NO and PGE2 release induced by IL-1beta. Inhibition of
      Npr2 with P19 maintained catabolic activities whilst specific agonism of Npr3
      with cANF4-23 had the opposite effect and reduced NO and PGE2 release. Co
      stimulation with CNP and dynamic compression enhanced anabolic activities and
      inhibited catabolic effects induced by IL-1beta. The presence of CNP and the Npr2
      antagonist abolished the anabolic response to mechanical loading and prevented
      loading-induced inhibition of NO and PGE2 release. In contrast, the presence of
      the Npr3 agonist had the opposite effect and increased GAG synthesis and cGMP
      levels in response to mechanical loading and reduced NO and PGE2 release
      comparable to control samples. In addition, CNP concentration and natriuretic
      peptide receptor expression were increased with dynamic compression. CONCLUSIONS:
      Mechanical loading mediates endogenous CNP release leading to increased
      natriuretic peptide signalling. The loading-induced CNP/Npr2/cGMP signalling
      route mediates anabolic events and prevents catabolic activities induced by IL
      1beta. The CNP pathway therefore represents a potentially chondroprotective
      intervention for patients with OA, particularly when combined with
      physiotherapeutic approaches to stimulate biomechanical signals.

PMID- 23883593
TI  - Performance-based tests to assess physical function in osteoarthritis of the hip
      or knee: comment and proposal.

PMID- 23883594
TI  - OARSI recommended performance-based tests to assess physical function in
      osteoarthritis of the hip or knee: authors' reply.

PMID- 23883595
TI  - Interferon regulatory factor 5 and autoimmune lupus.
AB  - Systemic lupus erythematosus (SLE) is a severe multi-system autoimmune disease,
      whereas interferon regulatory factor (IRF) 5 belongs to the family of
      transcription factors that modulate immune system activities. Recently, many
      lines of investigations suggested that IRF5 gene polymorphisms are closely
      associated with the disease onset of SLE. Indeed, expressed in B cells, dendritic
      cells (DCs), monocytes and macrophages, IRF5 could significantly affect these
      immune cells participating in the pathogenesis of SLE, and numerous studies
      implied that this transcription factor is mechanistically linked to the disease
      progression. Here, we comprehensively review the updated evidence indicating the
      roles of IRF5 in autoimmune lupus. Hopefully, the information obtained will lead
      to a better understanding of the pathogenesis and development of novel
      therapeutic strategies for the systemic autoimmune disease.

PMID- 23883596
TI  - Pharmacotherapeutic strategies for allergic rhinitis: matching treatment to
      symptoms, disease progression, and associated conditions.
AB  - The selection of specific pharmacotherapy for patients with allergic rhinitis
      (AR) depends on several factors, including age, most prominent symptoms, symptom
      severity, patient preference, cost, and comorbid conditions. Guidelines focus on
      immediate symptoms and monotherapy. However, given the often variable course of
      disease, understanding symptom patterns, and recommending intervention
      transitions among agents and classes (and from alternative single and combination
      medications) can aid in optimization of treatment. This review focuses on
      considerations for combination therapy for AR, particularly in the context of
      step-up and step-down treatment, and individual symptoms and comorbidities that
      may benefit from such treatment (e.g., asthma). Relevant clinical studies for
      treatment of AR and of AR with comorbid asthma and information on treatment
      guidelines were identified through MEDLINE searches from inception through 2012.
      Search terms and phrases included "allergic rhinitis," "asthma," "treatment
      guidelines," and "stepwise treatment." Stepped methodology is individualized
      according to patient-specific factors and severity of disease. A possible step
      up/step-down approach might move through five stages: step 1, for mild
      intermittent symptoms, intranasal or oral antihistamine, as needed; step 2, daily
      intranasal antihistamine (an oral antihistamine or leukotriene antagonist may be
      considered as an alternative); step 3, daily intranasal corticosteroids (INS);
      step 4, combination INS and intranasal antihistamines; step 5, further add-on
      therapy options in severe cases. A step-up/step-down approach to AR
      pharmacotherapy based on patient response may hold the potential for optimal
      control of AR symptoms while minimizing side effects and cost of treatment. 

PMID- 23883597
TI  - Chronic rhinosinusitis: epidemiology and cost.
AB  - Chronic rhinosinusitis (CRS) is one of the most common chronic diseases and is
      associated with a high socioeconomic burden from direct and indirect costs. Its
      estimated prevalence ranges widely, from 2 to 16%. It is more common in female
      subjects, aged 18-64 years, and in southern and midwestern regions of the United
      States. CRS is more prevalent in patients with comorbid diseases such as asthma,
      chronic obstructive pulmonary disease, and environmental allergies. Few studies
      examine patient ethnicity, socioeconomic status, geographic location, and
      cultural factors in CRS populations. This article provides an overview of the
      epidemiology, racial variations, and economic burden of CRS. 

PMID- 23883598
TI  - Exercise-induced bronchospasm, asthma control, and obesity.
AB  - Exercise-induced bronchospasm (EIB) commonly affects patients with asthma.
      However, the relationship between EIB and asthma control remains unclear.
      Exercise limitation due to asthma might lead to reduced physical activity, but
      little information is available regarding obesity and EIB in asthma. A recent
      survey evaluated the frequency of EIB and exercise-related respiratory symptoms
      in a large number of patients with asthma. The survey results were reanalyzed to
      address any relationship between EIB and asthma control and obesity. A nationwide
      random sample of children aged 4-12 years (n = 250), adolescents aged 13-17 years
      (n = 266), and adults aged >=18 years (n = 1001) with asthma were interviewed by
      telephone. Questions in the survey addressed asthma symptoms in general,
      medication use, and height and weight. Asthma control was categorized using
      established methods in the Expert Panel Report 3. Body mass index (BMI) was
      calculated using standard nomograms and obesity was defined as a BMI >= 30
      kg/m(2). Most children (77.6%), adolescents (71.1%), and adults (83.1%) had
      either "not well" or "very poorly" controlled asthma. Children with "not well"
      controlled asthma reported a history of EIB significantly more often than those
      with "well" controlled" asthma. Asthma patients of all ages who had "not well"
      and "very poorly" controlled asthma described multiple (four or more) exercise
      related respiratory symptoms significantly more often than those with "well
      controlled" asthma. Obesity was significantly more common in adolescents with
      "not well" and "very poorly" controlled asthma and adults with "very poorly"
      controlled asthma. Children, adolescents, and adults with asthma infrequently
      have well-controlled disease. A history of EIB and exercise-related respiratory
      symptoms occur more commonly in patients with not well and very poorly controlled
      asthma. Obesity was found more often in adolescents and adults, but not children,
      with asthma, which was not well and very poorly controlled. 

PMID- 23883599
TI  - A retrospective analysis comparing subjects with isolated and coexistent vocal
      cord dysfunction and asthma.
AB  - Vocal cord dysfunction (VCD) is often misdiagnosed as asthma or complicates
      coexisting asthma. This study aimed to identify distinguishing clinical
      characteristics in patients with VCD, asthma, and coexisting VCD and asthma. We
      conducted a retrospective analysis of demographic and clinical data from 292
      patients with VCD, asthma, coexisting VCD and asthma, and control subjects from
      an outpatient university asthma/allergy clinic. Concomitant asthma was present in
      32.6% of VCD subjects. Overall, 42.4 % of all VCD subjects were previously
      misdiagnosed as having asthma for an average of 9.0 years. Upper airway symptoms
      were more prevalent in the VCD population and nocturnal apnea was more prevalent
      in comorbid VCD and asthma compared with either condition alone. Irritable bowel
      syndrome and chronic pain were identified as new comorbidities associated with
      VCD. VCD subjects who had been misdiagnosed with asthma had significantly more
      health care and asthma medication use compared to VCD subjects who had not
      mimicked asthma. There was no difference in asthma severity between those with
      and without VCD. Comorbid VCD and asthma led to an increase in long-acting beta
      agonist use only, but no difference in health care usage, compared with asthma
      alone. These findings suggest that the main morbidity associated with VCD may not
      lie in its inherent disease process, but instead in its ability to mimic asthma. 

PMID- 23883600
TI  - The spectrum of aeroallergen sensitization in children diagnosed with asthma
      during first 2 years of life.
AB  - Aeroallergens may trigger symptoms in sensitized children with asthma.
      Documentation of sensitization is crucial to enable effective implementation of
      measures to prevent asthma exacerbations. To document the sensitization patterns
      of very young children (<=2 years) with asthma, we retrospectively analyzed the
      skin-prick test (SPT) results of the largest referral center in the country.
      During a 4-year period, 432 children (median age, 1.21 years; male/female, 2.35)
      were referred. All patients had recurrent wheezing attacks and good response to
      inhaled bronchodilators and were diagnosed with asthma by their referring
      physician. SPT with eight aeroallergens (grass mix, weed mix, tree mix, mold mix,
      house-dust mite, cockroach, cat, and dog) was performed in 209 patients (full
      panel group) and the remaining 223 were tested only with a mixture of two house
      dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae; house
      dust mite group). The sensitization rates in house-dust mite and full panel
      groups were 3.2% (7/223) and 3.3% (7/209), respectively. Univariate and
      multivariate modeling was unable to identify a predictor for the presence of
      aeroallergen sensitization. During first 2 years of life, low rates of
      aeroallergen sensitization and lack of predictors of sensitization in children
      with asthma suggest that skin testing for aeroallergens may not be a routine
      procedure. When there is a high index of suspicion, testing only for indoor
      aeroallergens including house-dust mites, molds, and pets may identify the
      majority of sensitized children. 

PMID- 23883601
TI  - Total IgE at 6 months predicts remittance or persistence of atopic dermatitis at
      14 months.
AB  - Some patients with infantile atopic dermatitis (AD) achieve remission around 1
      year old, but in others it persists. The difference between them is unclear. We
      performed a birth cohort study to find the markers predicting the outcome of
      infantile AD. We followed up a cohort (n = 314) from birth to 14 months of age,
      and cord blood was taken from the participants. Some of them (n = 144) had a
      physical examination and a blood test at 6 and 14 months of age. The subjects who
      had AD at 6 months (n = 34) were divided into two groups, named the transient
      group (those who had no AD at 14 months of age; n = 16) and the persistent group
      (those who still had AD at 14 months of age; n = 18). Then, laboratory data were
      compared between these two groups. Percentage of CD8 in cord blood lymphocytes
      and total IgE at 6 months of age in the persistent group was significantly higher
      than those of the transient group. The area under the curves of a receiver
      operating characteristic analysis were 0.792 (p = 0.007) and 0.722 (p = 0.027).
      In the persistent group, total IgE, percentages of T-helper (Th) 2 and
      phytohemagglutinin-induced IL-4 production from peripheral blood mononuclear
      cells at 14 months of age were also significantly higher than those of the
      transient group. Thus Th2 polarization in the persistent group was confirmed. In
      clinical use, total IgE at 6 months of age is the most useful predictive marker
      to know the outcome of infantile AD. The clinical trial registration ID is
      UMIN000002926. 

PMID- 23883602
TI  - Serum 25-hydroxyvitamin D concentrations and waning pneumococcal antibody titers
      among individuals with atopy.
AB  - Serum 25-hydroxyvitamin D (25[OH]D) concentrations are positively associated with
      pneumococcal antibody titers (PATs) in subjects with atopy or asthma. Little is
      known about the association of serum 25(OH)D concentrations and the waning of
      PATs over time in subjects with or without atopy. This study was designed to
      determine whether serum 25(OH)D concentrations are associated with waning of PATs
      and if such relationship is modified by atopic conditions. The study was designed
      as a prospective cohort study, which followed 20 asthmatic patients and 19
      individuals without asthma for an average of 12 months. We measured PATs and
      serum 25(OH)D concentrations at baseline and at a subsequent follow-up visit.
      Asthma was ascertained by predetermined criteria. The association between serum
      25(OH)D concentrations and PATs was determined by Pearson's correlation
      coefficient and a least square model. Of the 39 children and adults, 21(53%) were
      male subjects, all were white, and 6 (15%) were children. There was an overall
      negative correlation between serum 25(OH)D concentrations and the decrease of
      PATs during follow-up (r = -0.47; p = 0.004), suggesting that higher 25(OH)D
      concentrations were associated with a reduction in waning of PATs over time.
      Controlling for follow-up duration and pneumococcal colonization, these trends
      were significant among asthmatic patients but not in individuals without asthma.
      Similar trends were observed for individuals with or without other atopic
      conditions. Serum 25(OH)D concentrations are inversely associated with the waning
      of PATs over time, especially individuals with asthma and other atopy conditions.
      These study findings deserve further investigation. 

PMID- 23883603
TI  - The clinical dilemma of "silent desensitization" in aspirin-exacerbated
      respiratory disease.
AB  - Aspirin desensitization is a treatment option for patients with aspirin
      exacerbated respiratory disease (AERD). Some patients with an excellent history
      of aspirin or nonsteroidal anti-inflammatory drug (NSAID) reactions have negative
      aspirin challenges/desensitization. This study discusses the clinical entity of
      silent desensitization in AERD and the dilemma that this presents to the
      practicing allergist/immunologist. We discuss a series of patients with a strong
      history of NSAID reactions who initially underwent a negative challenge/silent
      desensitization. These patients were subsequently proven to have AERD after a
      second positive aspirin challenge. Silent desensitization is an uncommon but
      important outcome to recognize in AERD. Clinicians performing aspirin
      desensitization should understand that this can occur and consider a second
      confirmatory aspirin challenge in some patients. 

PMID- 23883604
TI  - Recurrent perioperative anaphylaxis in a 54-year-old man.
AB  - Reports suggest that perioperative anaphylaxis in patients undergoing general
      anesthesia range from 1 in 5000 to 1 in 20,000 with mortality rates as high as
      9%. Because of the variety of medications that are used for general anesthesia
      and the rapid succession in which they are administered, it is often difficult to
      determine the etiology of a severe allergic episode in this setting. Antibiotics
      and anesthetics are notorious for precipitating allergic reactions and are often
      implicated. Other perioperative exposures and patient risk factors must also be
      considered. In this article, we describe the case of a patient who exhibited
      recurrent anaphylaxis episodes while trying to undergo a vital cardiac surgery. 

PMID- 23883605
TI  - For the patient.

PMID- 23883606
TI  - Carbon sandwich preparation preserves quality of two-dimensional crystals for
      cryo-electron microscopy.
AB  - Electron crystallography is an important method for determining the structure of
      membrane proteins. In this paper, we show the impact of a carbon sandwich
      preparation on the preservation of crystalline sample quality, using
      characteristic examples of two-dimensional (2D) crystals from gastric H(+),K(+)
      ATPase and their analyzed images. Compared with the ordinary single carbon
      support film preparation, the carbon sandwich preparation dramatically enhanced
      the resolution of images from flat sheet 2D crystals. As water evaporation is
      restricted in the carbon-sandwiched specimen, the improvement could be due to the
      strong protective effect of the retained water against drastic changes in the
      environment surrounding the specimen, such as dehydration and increased salt
      concentrations. This protective effect by the carbon sandwich technique helped to
      maintain the inherent and therefore best crystal conditions for analysis.
      Together with its strong compensation effect for the image shift due to beam
      induced specimen charging, the carbon sandwich technique is a powerful method for
      preserving crystals of membrane proteins with larger hydrophilic regions, such as
      H(+),K(+)-ATPase, and thus constitutes an efficient and high-quality method for
      collecting data for the structural analysis of these types of membrane proteins
      by electron crystallography.

PMID- 23883608
TI  - Polymorphisms of CD44 gene and nasopharyngeal carcinoma susceptibility in a
      Chinese population.
AB  - As members of adhesion molecule families, CD44 transmembrane glycoproteins have
      been originally thought to be essential for the formation of multicellular
      organisms and soon recognised to be able to initiate metastatic spread of tumour
      cells. To investigate the association between CD44 polymorphisms and
      nasopharyngeal carcinoma (NPC), we carried out a two-stage case-control study in
      906 patients and 943 healthy controls in Eastern populations. Five single
      nucleotide polymorphisms of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G,
      rs11821102G>A and rs713330T>C) with proper frequency were selected from the
      HapMap database and genotyped with matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry. Compared with the most common rs13347CC
      genotype, CT+TT genotypes significantly increased individuals' susceptibility to
      NPC (odds ratio = 2.58, 95% confidence interval = 2.13-3.13). Furthermore, our
      transient transfection focusing on reporter gene expression modulated by CD44
      3'UTR demonstrated that the presence of an rs13347T allele led to greater
      transcriptional activity than the C allele. Similarly, more CD44 expression was
      shown in rs13347T carriers than C carriers in our western blotting results. All
      these findings suggest that CD44 rs13347C>T polymorphism may affect NPC
      development by improving CD44 expression. 

PMID- 23883607
TI  - Microarray characterization of gene expression changes in blood during acute
      ethanol exposure.
AB  - BACKGROUND: As part of the civil aviation safety program to define the adverse
      effects of ethanol on flying performance, we performed a DNA microarray analysis
      of human whole blood samples from a five-time point study of subjects
      administered ethanol orally, followed by breathalyzer analysis, to monitor blood
      alcohol concentration (BAC) to discover significant gene expression changes in
      response to the ethanol exposure. METHODS: Subjects were administered either
      orange juice or orange juice with ethanol. Blood samples were taken based on BAC
      and total RNA was isolated from PaxGeneTM blood tubes. The amplified cDNA was
      used in microarray and quantitative real-time polymerase chain reaction (RT-qPCR)
      analyses to evaluate differential gene expression. Microarray data was analyzed
      in a pipeline fashion to summarize and normalize and the results evaluated for
      relative expression across time points with multiple methods. Candidate genes
      showing distinctive expression patterns in response to ethanol were clustered by
      pattern and further analyzed for related function, pathway membership and common
      transcription factor binding within and across clusters. RT-qPCR was used with
      representative genes to confirm relative transcript levels across time to those
      detected in microarrays. RESULTS: Microarray analysis of samples representing 0%,
      0.04%, 0.08%, return to 0.04%, and 0.02% wt/vol BAC showed that changes in gene
      expression could be detected across the time course. The expression changes were
      verified by qRT-PCR.The candidate genes of interest (GOI) identified from the
      microarray analysis and clustered by expression pattern across the five BAC
      points showed seven coordinately expressed groups. Analysis showed function-based
      networks, shared transcription factor binding sites and signaling pathways for
      members of the clusters. These include hematological functions, innate immunity
      and inflammation functions, metabolic functions expected of ethanol metabolism,
      and pancreatic and hepatic function. Five of the seven clusters showed links to
      the p38 MAPK pathway. CONCLUSIONS: The results of this study provide a first look
      at changing gene expression patterns in human blood during an acute rise in blood
      ethanol concentration and its depletion because of metabolism and excretion, and
      demonstrate that it is possible to detect changes in gene expression using total
      RNA isolated from whole blood. The analysis approach for this study serves as a
      workflow to investigate the biology linked to expression changes across a time
      course and from these changes, to identify target genes that could serve as
      biomarkers linked to pilot performance.

PMID- 23883609
TI  - Sea-level rise caused by climate change and its implications for society.
AB  - Sea-level rise is a major effect of climate change. It has drawn international
      attention, because higher sea levels in the future would cause serious impacts in
      various parts of the world. There are questions associated with sea-level rise
      which science needs to answer. To what extent did climate change contribute to
      sea-level rise in the past? How much will global mean sea level increase in the
      future? How serious are the impacts of the anticipated sea-level rise likely to
      be, and can human society respond to them? This paper aims to answer these
      questions through a comprehensive review of the relevant literature. First, the
      present status of observed sea-level rise, analyses of its causes, and future
      projections are summarized. Then the impacts are examined along with other
      consequences of climate change, from both global and Japanese perspectives.
      Finally, responses to adverse impacts will be discussed in order to clarify the
      implications of the sea-level rise issue for human society.(Communicated by
      Kiyoshi HORIKAWA, M.J.A.). 

PMID- 23883610
TI  - Bio-recognition and functional lipidomics by glycosphingolipid transfer
      technology.
AB  - Through glycosphingolipid biochemical research, we developed two types of
      transcription technologies. One is a biochemical transfer of glycosphingolipids
      to peptides. The other is a physicochemical transfer of glycosphingolipids in
      silica gel to the surface of a plastic membrane. Using the first technology, we
      could prepare peptides which mimic the shapes of glycosphingolipid molecules by
      biopanning with a phage-displayed peptide library and anti-glycosphingolipid
      antibodies as templates. The peptides thus obtained showed biological properties
      and functions similar to those of the original glycosphingolipids, such as lectin
      binding, glycosidase modulation, inhibition of tumor metastasis and immune
      response against the original antigen glycosphingolipid, and we named them glyco
      replica peptides. The results showed that the newly prepared peptides could be
      used effectively as a bio-recognition system and suggest that the glyco-replica
      peptides can be widely applied to therapeutic fields. Using the second
      technology, we could establish a functional lipidomics with a thin-layer
      chromatography-blot/matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (TLC-Blot/MALDI-TOF MS) system. By transferring
      glycosphingolipids on a plastic membrane surface from a TLC plate, innovative
      biochemical approaches such as simple purification of individual
      glycosphingolipids, binding studies, and enzyme reactions could be developed. The
      combinations of these biochemical approaches and MALDI-TOF MS on the plastic
      membrane could provide new strategies for glycosphingolipid science and the field
      of lipidomics. In this review, typical applications of these two transfer
      technologies are introduced.(Communicated by Kunihiko SUZUKI, M.J.A.). 

PMID- 23883611
TI  - Metabolism of amyloid beta peptide and pathogenesis of Alzheimer's disease.
AB  - The conversion of what has been interpreted as "normal brain aging" to
      Alzheimer's disease (AD) via transition states, i.e., preclinical AD and mild
      cognitive impairment, appears to be a continuous process caused primarily by
      aging-dependent accumulation of amyloid beta peptide (Abeta) in the brain. This
      notion however gives us a hope that, by manipulating the Abeta levels in the
      brain, we may be able not only to prevent and cure the disease but also to
      partially control some very significant aspects of brain aging. Abeta is
      constantly produced from its precursor and immediately catabolized under normal
      conditions, whereas dysmetabolism of Abeta seems to lead to pathological
      deposition upon aging. We have focused our attention on elucidation of the
      unresolved mechanism of Abeta catabolism in the brain. In this review, I describe
      a new approach to prevent AD development by reducing Abeta burdens in aging
      brains through up-regulation of the catabolic mechanism involving neprilysin that
      can degrade both monomeric and oligomeric forms of Abeta. The strategy of
      combining presymptomatic diagnosis with preventive medicine seems to be the most
      pragmatic in both medical and socioeconomical terms.(Communicated by Kunihiko
      SUZUKI, M.J.A.). 

PMID- 23883612
TI  - Combined effects of estrogen deficiency and cadmium exposure on calcified hard
      tissues: animal model relating to itai-itai disease in postmenopausal women.
AB  - Using ovariectomized rats as a model of postmenopausal women, we studied the
      effects of estrogen (Es) deficiency and in combination with cadmium (Cd) exposure
      on the calcified hard tissues related to the development of itai-itai disease. Es
      deficiency suppressed the synthesis of carbonic anhydrase required for the
      crystal nucleation process, causing the crystal structure defects in the tooth
      enamel. Regarding the combined effects of Es deficiency and Cd exposure on the
      bone, in which rats were given drinking water containing Cd ions, soft X-ray
      radiography revealed a development of labyrinthine pattern in the calvaria, and
      micro-computed tomography demonstrated the declining trabecular architecture of
      the tibia, suggesting Cd-induced osteoporotic change. Further, electron
      microscopy showed the increase of amorphous minerals in the calvaria. In
      conclusion, the combined effects of Es deficiency and Cd exposure can be
      responsible for accelerating the declining bone strength together with the
      crystal structure defects resulting in the preferential occurrence of itai-itai
      disease in postmenopausal women.(Communicated by Tatsuo SUDA, M.J.A.). 

PMID- 23883614
TI  - Helium ion microscopy of graphene: beam damage, image quality and edge contrast.
AB  - A study to analyse beam damage, image quality and edge contrast in the helium ion
      microscope (HIM) has been undertaken. The sample investigated was graphene. Raman
      spectroscopy was used to quantify the disorder that can be introduced into the
      graphene as a function of helium ion dose. The effects of the dose on both
      freestanding and supported graphene were compared. These doses were then
      correlated directly to image quality by imaging graphene flakes at high
      magnification. It was found that a high magnification image with a good signal to
      noise ratio will introduce very significant sample damage. A safe imaging dose of
      the order of 10(13) He(+) cm(-2) was established, with both graphene samples
      becoming highly defective at doses over 5 * 10(14) He(+) cm(-2).The edge contrast
      of a freestanding graphene flake imaged in the HIM was then compared with the
      contrast of the same flake observed in a scanning electron microscope and a
      transmission electron microscope. Very strong edge sensitivity was observed in
      the HIM. This enhanced edge sensitivity over the other techniques investigated
      makes the HIM a powerful nanoscale dimensional metrology tool, with the
      capability of both fabricating and imaging features with sub-nanometre
      resolution. 

PMID- 23883613
TI  - Feasibility of fully automated closed-loop glucose control using continuous
      subcutaneous glucose measurements in critical illness: a randomized controlled
      trial.
AB  - INTRODUCTION: Closed-loop (CL) systems modulate insulin delivery according to
      glucose levels without nurse input. In a prospective randomized controlled trial,
      we evaluated the feasibility of an automated closed-loop approach based on
      subcutaneous glucose measurements in comparison with a local sliding-scale
      insulin-therapy protocol. METHODS: Twenty-four critically ill adults
      (predominantly trauma and neuroscience patients) with hyperglycemia (glucose,
      >=10 mM) or already receiving insulin therapy, were randomized to receive either
      fully automated closed-loop therapy (model predictive control algorithm directing
      insulin and 20% dextrose infusion based on FreeStyle Navigator continuous
      subcutaneous glucose values, n = 12) or a local protocol (n = 12) with
      intravenous sliding-scale insulin, over a 48-hour period. The primary end point
      was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM.
      RESULTS: The time when glucose was in the target range was significantly
      increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to
      39.9), P = 0.001; median (interquartile range)), and so was time in wider
      targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P <= 0.002), reflecting a reduced
      glucose exposure >8 and >10 mM (P <= 0.002). Mean glucose was significantly lower
      during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without
      hypoglycemia (<4 mM) during either therapy. CONCLUSIONS: Fully automated closed
      loop control based on subcutaneous glucose measurements is feasible and may
      provide efficacious and hypoglycemia-free glucose control in critically ill
      adults. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01440842.

PMID- 23883615
TI  - Origin and evolution of the Italian subterranean termite Reticulitermes lucifugus
      (Blattodea, Termitoidae, Rhinotermitidae).
AB  - The Holarctic genus Reticulitermes shows seven species within the Mediterranean
      Basin. While phylogeny and systematics at continental level has been deeply
      investigated, a few studies concentrated on local ranges. To gain a clearer
      picture of the diversity and evolution of the Italian species Reticulitermes
      lucifugus, we analyzed the mitochondrial cytochrome oxidase II (COII) gene marker
      in newly collected colonies across the Peninsula. Data were gathered with all R.
      lucifugus sequences available from previous studies; COII sequences of the
      closely related Iberian taxa were also added to the data set. Maximum-likelihood,
      median-joining and statistical parsimony network elaborations on the resulting
      119 colonies all agreed in indicating that: (i) the Sardo-Corsican subspecies R.
      lucifugus corsicus, strictly related to Southern Italian populations (including
      the Sicilian ones), is phylogenetically closer to the Iberian Reticulitermes
      grassei; and (ii) R. lucifugus lucifugus peninsular populations are structured
      into three clusters. The phylogenetic relationships and the biogeography of
      extant taxa suggest a scenario in which R. lucifugus ancestors colonized the
      Italian region through the Sardo-Corsican microplate during its Oligocene-Miocene
      anticlockwise rotation. Moreover, well after the colonization took place,
      northward range expansion might have produced the presently observed genetic
      diversity, as inferred from haplotype and nucleotide diversity estimates. On the
      whole, this study highlights the evolution of Italian Reticulitermes taxa and
      supports the importance of a wide taxon sampling especially when dealing with
      organisms easily dispersed by human activities. 

PMID- 23883616
TI  - The effectiveness of a Web-based personalized feedback and social norms alcohol
      intervention on United Kingdom university students: randomized controlled trial.
AB  - BACKGROUND: Alcohol consumption in the student population continues to be cause
      for concern. Building on the established evidence base for traditional brief
      interventions, interventions using the Internet as a mode of delivery are being
      developed. Published evidence of replication of initial findings and ongoing
      development and modification of Web-based personalized feedback interventions for
      student alcohol use is relatively rare. The current paper reports on the
      replication of the initial Unitcheck feasibility trial. OBJECTIVE: To evaluate
      the effectiveness of Unitcheck, a Web-based intervention that provides instant
      personalized feedback on alcohol consumption. It was hypothesized that use of
      Unitcheck would be associated with a reduction in alcohol consumption. METHODS: A
      randomized control trial with two arms (control=assessment only;
      intervention=fully automated personalized feedback delivered using a Web-based
      intervention). The intervention was available week 1 through to week 15. Students
      at a UK university who were completing a university-wide annual student union
      electronic survey were invited to participate in the current study. Participants
      (n=1618) were stratified by sex, age group, year of study, self-reported alcohol
      consumption, then randomly assigned to one of the two arms, and invited to
      participate in the current trial. Participants were not blind to allocation. In
      total, n=1478 (n=723 intervention, n=755 control) participants accepted the
      invitation. Of these, 70% were female, the age ranged from 17-50 years old, and
      88% were white/white British. Data were collected electronically via two
      websites: one for each treatment arm. Participants completed assessments at weeks
      1, 16, and 34. Assessment included CAGE, a 7-day retrospective drinking diary,
      and drinks consumed per drinking occasion. RESULTS: The regression model
      predicted a monitoring effect, with participants who completed assessments
      reducing alcohol consumption over the final week. Further reductions were
      predicted for those allocated to receive the intervention, and additional
      reductions were predicted as the number of visits to the intervention website
      increased. CONCLUSIONS: Unitcheck can reduce the amount of alcohol consumed, and
      the reduction can be sustained in the medium term (ie, 19 weeks after
      intervention was withdrawn). The findings suggest self-monitoring is an active
      ingredient to Web-based personalized feedback.

PMID- 23883620
TI  - Electronic properties of supracrystals of Au nanocrystals: influence of thickness
      and nanocrystallinity.
AB  - Well-defined superlattices of colloidal nanocrystals, called supracrystals, are
      expected to have interesting physical properties. While the electronic properties
      of thin supracrystals have been extensively studied in the planar configuration,
      little is known about electron transport through micrometer-thick supracrystals.
      Here, we investigate the electronic properties of supracrystals made of Au
      nanocrystals with diameters of 5, 6, 7 and 8 nm using scanning tunneling
      microscopy/spectroscopy at low temperatures. The current-voltage characteristics
      show power-law dependences with exponents varying strongly with supracrystal
      thicknesses from 30 nm to a few microns. The crystallinity of these nanocrystals,
      called nanocrystallinity, is exclusively single domain for 5 nm nanocrystals and
      a mixture of single and polycrystalline phase for 6, 7 and 8 nm nanocrystals. We
      observed that supracrystals made of 5 nm nanocrystals have a different behavior
      than supracrystals made of 6, 7 and 8 nm nanocrystals and this might be related
      to the nanocrystallinity. These results help us to better understand the electron
      transport mechanism in such miniscule structures built from a bottom-up approach.

PMID- 23883618
TI  - Challenges and opportunities for international cooperative studies in pediatric
      hematopoeitic cell transplantation: priorities of the Westhafen Intercontinental
      Group.
AB  - More than 20% of allogeneic hematopoietic cell transplantations (HCTs) are
      performed in children and adolescents at a large number of relatively small
      centers. Unlike adults, at least one-third of HCTs in children are performed for
      rare, nonmalignant indications. Clinical trials to improve HCT outcomes in
      children have been limited by small numbers and these pediatric-specific
      features. The need for a larger number of pediatric HCT centers to participate in
      trials has led to the involvement of international collaborative groups.
      Representatives of the Pediatric Blood and Marrow Transplant Consortium, European
      Group for Blood and Marrow Transplantation's Pediatric Working Group,
      International Berlin-Frankfurt-Munster (iBFm) Stem Cell Transplantation
      Committee, and Children's Oncology Group's Hematopoietic Stem Cell
      Transplantation Discipline Committee met on October 3, 2012, in Frankfurt,
      Germany to develop a consensus on the highest priorities in pediatric HCT. In
      addition, it explored the creation of an international consortium to develop
      studies focused on HCT in children and adolescents. This meeting led to the
      creation of an international HCT network, dubbed the Westhafen Intercontinental
      Group, to develop worldwide priorities and strategies to address pediatric HCT
      issues. This review outlines the priorities of need as identified by this
      consensus group.

PMID- 23883619
TI  - Linked decreases in liver kinase B1 and AMP-activated protein kinase activity
      modulate matrix catabolic responses to biomechanical injury in chondrocytes.
AB  - INTRODUCTION: AMP-activated protein kinase (AMPK) maintains cultured chondrocyte
      matrix homeostasis in response to inflammatory cytokines. AMPK activity is
      decreased in human knee osteoarthritis (OA) chondrocytes. Liver kinase B1 (LKB1)
      is one of the upstream activators of AMPK. Hence, we examined the relationship
      between LKB1 and AMPK activity in OA and aging cartilages, and in chondrocytes
      subjected to inflammatory cytokine treatment and biomechanical compression
      injury, and performed translational studies of AMPK pharmacologic activation.
      METHODS: We assessed activity (phosphorylation) of LKB1 and AMPKalpha in mouse
      knee OA cartilage, in aging mouse cartilage (6 to 24 months), and in chondrocytes
      after mechanical injury by dynamic compression, via immunohistochemistry or
      western blot. We knocked down LKB1 by siRNA transfection. Nitric oxide, matrix
      metalloproteinase (MMP)-3, and MMP-13 release were measured by Griess reaction
      and ELISA, respectively. RESULTS: Knockdown of LKB1 attenuated chondrocyte AMPK
      activity, and increased nitric oxide, MMP-3 and MMP-13 release (P <0.05) in
      response to IL-1beta and TNFalpha. Both LKB1 and AMPK activity were decreased in
      mouse knee OA and aged knee cartilage, and in bovine chondrocytes after
      biomechanical injury. Pretreatment of bovine chondrocytes with AMPK activators
      AICAR and A-769662 inhibited both AMPKalpha dephosphorylation and catabolic
      responses after biomechanical injury. CONCLUSION: LKB1 is required for
      chondrocyte AMPK activity, thereby inhibiting matrix catabolic responses to
      inflammatory cytokines. Concurrent loss of LKB1 and AMPK activity in articular
      chondrocytes is associated with OA, aging and biomechanical injury. Conversely,
      pharmacologic AMPK activation attenuates catabolic responses to biomechanical
      injury, suggesting a potentially novel approach to inhibit OA development and
      progression.

PMID- 23883617
TI  - Clinical neuropathology practice guide 5-2013: markers of neuronal maturation.
AB  - This review surveys immunocytochemical and histochemical markers of neuronal
      lineage for application to tissue sections of fetal and neonatal brain. They
      determine maturation of individual nerve cells as the tissue progresses to mature
      architecture. From a developmental perspective, neuronal markers are all about
      timing. These diverse cellular labels may be classified in two ways: 1) time of
      onset of expression (early; intermediate; late); 2) labeling of subcellular
      structures or metabolic functions (nucleoproteins; synaptic vesicle proteins;
      enolases; cytoskeletal elements; calcium-binding; nucleic acids; mitochondria).
      Apart from these positive markers of maturation, other negative markers are
      expressed in primitive neuroepithelial cells and early stages of neuroblast
      maturation, but no longer are demonstrated after initial stages of maturation.
      These examinations are relevant for studies of normal neuroembryology at the
      cellular level. In fetal and perinatal neuropathology they provide control
      criteria for application to malformations of the brain, inborn metabolic
      disorders and acquired fetal insults in which neuroblastic maturation may be
      altered. Disorders, in which cells differentiate abnormally, as in tuberous
      sclerosis and hemimegalencephaly, pose another yet aspect of mixed cellular
      lineage. The measurement in living patients, especially neonates, of serum and
      CSF levels of enolases, chromogranins and S-100 proteins as biomarkers of brain
      damage may potentially be correlated with their corresponding tissue markers at
      autopsy in infants who do not survive. The neuropathological markers here
      described can be performed in ordinary hospital laboratories, not just research
      facilities, and offer another dimension of diagnostic precision in interpreting
      abnormally developed fetal and postnatal brains. 

PMID- 23883621
TI  - Care plans and care planning in long-term conditions: a conceptual model.
AB  - The prevalence and impact of long-term conditions continues to rise. Care
      planning for people with long-term conditions has been a policy priority for
      chronic disease management in a number of health-care systems. However, patients
      and providers appear unclear about the formulation and implementation of care
      planning. Further work in this area is therefore required to inform the
      development, implementation and evaluation of future care planning initiatives.
      We distinguish between 'care planning' (the process by which health-care
      professionals and patients discuss, agree and review an action plan to achieve
      the goals or behaviour change of most relevance and concern to the patient) and a
      'care plan' (a written document recording the outcome of a care planning
      process). We propose a typology of care planning and care plans with three core
      dimensions: perspective (patient or professional), scope (a focus on goals or on
      behaviours) and networks (confined to the professional-patient dyad or extending
      to the entire care network). In addition, we draw on psychological models of
      mediation and moderation to outline potential mechanisms through which care
      planning and care plans may lead to improved outcomes for both patients and the
      wider health-care system. The proposed typology of care planning and care plans
      offered here, along with the model of the process by which care planning may
      influence outcomes, provide a useful framework for future policy developments and
      evaluations. Empirical work is required to explore the degree to which current
      care planning approaches and care plans can be described according to these
      dimensions, and the factors that determine which types of patients and
      professionals use which type of care plans. 

PMID- 23883622
TI  - Transferrin modified graphene oxide for glioma-targeted drug delivery: in vitro
      and in vivo evaluations.
AB  - Transferrin (Tf), an iron-transporting serum glycoprotein that binds to receptors
      overexpressed at the surface of glioma cells, was chosen as the ligand to develop
      Tf-conjugated PEGylated nanoscaled graphene oxide (GO) for loading and glioma
      targeting delivery of anticancer drug doxorubicin (Dox) (Tf-PEG-GO-Dox). Tf-GO
      with lateral dimensions of 100-400 nm exhibited a Dox loading ratio up to 115.4%.
      Compared with Dox-loaded PEGylated GO (PEG-GO-Dox) and free Dox, Tf-PEG-GO-Dox
      displayed greater intracellular delivery efficiency and stronger cytotoxicity
      against C6 glioma cells. A competition test showed that Tf was essential to
      glioma targeting in vitro. The HPLC assay for Dox concentration in tumor tissue
      and contrapart tissue of the brain demonstrated that Tf-PEG-GO-Dox could deliver
      more Dox into tumor in vivo. The life span of tumor bearing rats after the
      administration of Tf-PEG-GO-Dox was extended significantly compared to the rats
      treated with saline, Dox, and PEG-GO-Dox. In conclusion, we developed Tf-PEG-GO
      Dox which exhibited significantly improved therapeutic efficacy for glioma both
      in vitro and in vivo. 

PMID- 23883623
TI  - Pattern of condom use among clients at a Nigerian HIV Counseling and Testing
      Centre.
AB  - BACKGROUND: Studies in Nigeria have shown that the main route of HIV transmission
      is sexual intercourse and that effective condom use protects people against
      infection. The objective of this study was to determine the pattern of condom use
      among clients of a friendly HIV Counseling and Testing (HCT) Centre in Osogbo
      southwestern Nigeria. METHODS: This was a review of the HCT Centre records from
      2006 to 2010 retrieving socio-demographic information, sexual behaviour, condom
      use and result of HIV testing. Data obtained were analyzed using descriptive and
      inferential statistics. RESULTS: One thousand nine hundred and twenty-one client
      records were reviewed. The mean age of the study population was 35.4 (SD 10.5)
      years. The majority (53%) of the respondents were females, 232 (12%) were HIV
      positive, and 38.2% had multiple sexual partners. Only heterosexual vaginal sex
      was reported among the clients. Overall 45.2% of the clients did not use a condom
      in their last sexual act. Factors identified to be significantly associated with
      non-use of condoms were; younger age, having had higher education and positive
      HIV status. CONCLUSION: Unprotected heterosexual intercourse was common among the
      study population, indicating a need to step up HIV preventive programme through
      behavioural change communication strategy.

PMID- 23883624
TI  - Phospholipase C-gamma2 via p38 and ERK1/2 MAP kinase mediates diperoxovanadate
      asparagine induced human platelet aggregation and sCD40L release.
AB  - OBJECTIVE: Redox imbalance either inside platelets or in their immediate
      surroundings prove detrimental to their physiologic functions during haemostasis.
      This study was therefore aimed to assess the effect of peroxide radicals on
      platelet functions and underlying signalling mechanisms using asparagine
      conjugated diperoxovanadate (DPV-Asn). METHODS: Platelet aggregation, ATP
      secretion, TxB2 release, intra-platelet calcium mobilization, protein tyrosine
      phosphorylation, GPIIbIIIa activation by PAC1 labelling and sCD40L release
      (enzyme-linked immunosorbent assay) was monitored using various concentrations of
      DPV-Asn. Cell viability was assessed by Annexin V labelling, MTT assay, LDH
      leakage and mitochondrial membrane potential by JC-1. RESULTS: Platelet
      aggregation induced by DPV-Asn was chiefly regulated by dense granule secretion,
      thromboxane A2 (TxA2) generation, intra-platelet [Ca(2+)] influx, GPIIbIIIa
      activation and sCD40L release, which were significantly reduced in presence of
      U73122 (PLC inhibitor), aspirin (COX), SB203580 (p38 inhibitor), and PD98059 (ERK
      inhibitor). This was further corroborated by enhanced tyrosine phosphorylation of
      numerous platelet proteins including PLC-gamma2, which apparently played a
      central role in transducing peroxide signals to regulate [Ca(2+)] influx and
      phosphorylation of p38 and ERK1/2 MAP kinase. DISCUSSION: Peroxide radicals
      critically regulate the thrombo-inflammatory functions of platelets via the
      PLCgamma2-p38-ERK1/2-TxA2 pathway, which closely resembles the clinical scenario
      of various pathologies like hyperglycemia and atherosclerosis during which
      oxidative stress disrupts platelet functions.

PMID- 23883626
TI  - [Learn a lesson from quick medical responce against Great East Japan Earthquake
      and prospects of next-quake].

PMID- 23883625
TI  - Kinetics and protective role of autophagy in a mouse cecal ligation and puncture
      induced sepsis.
AB  - INTRODUCTION: It is not well understood whether the process of autophagy is
      accelerated or blocked in sepsis, and whether it is beneficial or harmful to the
      immune defense mechanism over a time course during sepsis. Our aim was to
      determine both the kinetics and the role of autophagy in sepsis. METHODS: We
      examined autophagosome and autolysosome formation in a cecal ligation and
      puncture (CLP) mouse model of sepsis (in C57BL/6N mice and GFP-LC3 transgenic
      mice), using western blotting, immunofluorescence, and electron microscopy. We
      also investigated the effect of chloroquine inhibition of autophagy on these
      processes. RESULTS: Autophagy, as demonstrated by increased LC3-II/LC3-I ratios,
      is induced in the liver, heart, and spleen over 24 h after CLP. In the liver,
      autophagosome formation peaks at 6 h and declines by 24 h. Immunofluorescent
      localization of GFP-LC3 dots (alone and with lysosome-associated membrane protein
      type 1 (LAMP1)), as well as electron microscopic examination, demonstrate that
      both autophagosomes and autolysosomes are increased after CLP, suggesting that
      intact autophagy mechanisms operate in the liver in this model. Furthermore,
      inhibition of autophagy process by chloroquine administration immediately after
      CLP resulted in elevated serum transaminase levels and a significant increase in
      mortality. CONCLUSIONS: All autophagy-related processes are properly activated in
      the liver in a mouse model of sepsis; autophagy appears to play a protective role
      in septic animals.

PMID- 23883627
TI  - [How should we achieve the urban planning aimed at healthy longevity? - From new
      attempt 'Aging in Place' in KASHIWA city].

PMID- 23883628
TI  - [The healthy future city in KASHIWANOHA].

PMID- 23883629
TI  - [Creating compact cities in a society with a declining and aging population].

PMID- 23883630
TI  - [City planning facing an aging society].

PMID- 23883631
TI  - [Urban development in the super-aging society].

PMID- 23883632
TI  - [The recovery program of the stricken area to which a supar-aged society is
      invited].

PMID- 23883633
TI  - [A cross-sectional study of sarcopenia in Japanese men and women: reference
      values and association with cardiovascular risk factors and metabolic syndrome].

PMID- 23883634
TI  - [Sarcopenia in community-dwelling elderly subjects in Japan: assessing muscle
      mass using bioimpedance analysis].

PMID- 23883635
TI  - [Sarcopenia and its risk factors in epidemiological study].
AB  - In sarcopenia, muscle volume and strength decrease with ageing, disturbing
      activity of daily life in the elderly. We investigated risk factors of sarcopenia
      including life-style, nutrition intake and past history in randomly selected
      community living population aged 40 years and over. The subjects were 1,783 men
      and 1,825 women. They were followed up 10 years and repeatedly measured, we made
      a total of 14,010 measurements. Smoking, lack of exercise, shortage of energy,
      protein, branched-chain amino acid intake, and low self-rated health were risk
      factors of sarcopenia determined by muscle volume in dual-energy x-ray
      absorptiometry (DXA). Risk factors of sarcopenia determined by physical
      performance were also investigated in subjects aged 65 years or over. Smoking
      increased risk of sarcopenia, and intakes of total energy, vitamin D, protein and
      branched-chain amino acid significantly decreased risk of sarcopenia. However,
      physical activity was not related to incidence of sarcopenia. 

PMID- 23883636
TI  - [Interventions for frailty and sarcopenia in community-dwelling elderly women].
AB  - OBJECTIVE: To investigate the effectiveness of exercise alone in improving
      frailty, and exercise with nutritional supplementation in improving sarcopenia.
      METHODS: Frailty: 131 community-dwelling elderly people over 75 years of age were
      randomly assigned to either the exercise group (n=66) or the control group
      (n=65). The exercise group was provided with a 60-minute comprehensive exercise
      program twice a week for 3 months. Sarcopenia: 155 community-dwelling elderly
      people over 75 years of age were randomly assigned to the exercise + amino acid
      group (n=39), exercise group (n=39), amino acid group (n=39) or control group
      (n=38). The exercise intervention included a comprehensive training program for
      60 minutes, provided twice a week for 3 months. The amino acid group ingested a
      leucine-rich essential amino acid supplementation (6 g/day) for 3 months.
      RESULTS: Frailty: in comparison to the non-frail elderly, muscle mass, bone
      mineral density, knee extension strength, and walking speed were significantly
      lower in the frail elderly; however, pain, fall rate, and osteoporosis history
      were greater in the frail elderly. The exercise intervention significantly
      improved bone mineral content and grip strength. Sarcopenia: appendicular
      skeletal muscle mass and walking speed were significantly improved by exercise or
      amino acid supplementation. However, muscle strength improved significantly only
      in the exercise + amino acid intervention. CONCLUSION: In the frail elderly,
      exercise was effective in enhancing bone mineral content and muscle strength;
      however, in order to increase leg muscle mass and strength in sarcopenic elderly,
      both exercise and amino acid supplementation may be necessary.

PMID- 23883637
TI  - [Comparison of quantitative image indexes of brain MRI between differentiates
      idiopathic normal pressure hydrocephalus and Alzheimer disease, predict positive
      response of the CSF drainage in possible idiopathic normal pressure
      hydrocephalus].
AB  - AIM: The clinical guidelines for idiopathic normal pressure hydrocephalus (iNPH)
      in Japan recommend cerebrospinal fluid (CSF) drainage. The positive response rate
      of the diagnostic CSF drainage is not very high because brain MRI findings of
      Alzheimer disease (AD) are similar to those of iNPH. Therefore, we sought to
      determine simple, quantitative indexes of head MRI to differentiate iNPH from AD
      and to predict positive response of the CSF drainage in possible iNPH. METHODS:
      Eighteen patients with the clinical criteria of possible iNPH who had undergone
      diagnostic CSF drainage were evaluated. Nineteen patients with the clinical
      criteria of probable AD were used as controls. VSRAD, Evans index, and previously
      reported indicators were measured on brain MRI in all patients. These parameters
      were compared between AD and iNPH, and between iNPH responders and non
      responders. RESULTS: VSRAD, Evans index, bifrontal index, width and height of the
      temporal horn, and the maximum height of the Sylvian fissure were higher in iNPH
      than AD. The cutoff value of the bifrontal index, width and height of the
      temporal horn, and maximum height of the Sylvian fissure were 0.31, 6.0 mm, 3.13
      mm, and 7.6 mm, respectively. The minimum thickness of the medial temporal lobe
      was higher in the CSF drainage responders than the non-responders. The cutoff
      value of the minimum thickness of the medial temporal lobe was 11.0 mm.
      CONCLUSIONS: Our results suggest that simple image indexes of brain MRI could
      distinguish iNPH from AD and predict positive response to CSF drainage in iNPH.

PMID- 23883638
TI  - [A study of factors influenced by self-efficacy for exercise among community
      dwelling elderly men in urban areas].
AB  - AIM: It is important to promote self-efficacy for exercise for developing
      exercise habit. The purpose of this study was to investigate factors influenced
      by self-efficacy for exercise among community-dwelling elderly men in urban
      areas. METHODS: The subjects were 69 elderly men (mean age of 74.2+/-2.0 SD) who
      had given approval for participation in the study. We examined the following
      factors: family situation, history of falls, frequency of going out, stage model
      of a change, self-efficacy for exercise, fall efficacy scale (FES), geriatric
      depression scale (GDS), subjective health, functional ability and motor function
      (5 m walking time, chair stand test-5times). Analysis of variance was used to
      assess a stage model of a change differences in self-efficacy for exercise and
      other measures. Correlation analysis and multiple regression analysis were
      performed to determine the relationships between self-efficacy for exercise and
      other measures. RESULTS: We found that self-efficacy of exercise, FES, GDS
      (p<0.01) and CST (p<0.05) vary depending on the stage model of change. Self
      efficacy for exercise was found to correlate with psychological factors and
      functional ability (|r|=0.47-0.67). Multiple regression analysis revealed that
      the independent factors related to self-efficacy for exercise were FES and GDS.
      CONCLUSION: FES and GDS were found to be significant and independent predictors
      of self-efficacy for exercise in community-dwelling elderly men in urban areas.
      We should consider not only the approach based on behavioral science but also
      mental support for depression and fear of falling to promote exercise self
      efficacy.

PMID- 23883639
TI  - [Development of weight-estimation formulae for the bedridden elderly requiring
      care].
AB  - AIM: Bedridden elderly persons requiring care need special body-weight
      measurement implements, and body-weighting assumes more difficult if they live at
      their own homes. Therefore, we tried to design a new weight-estimation formulae
      using various anthropometric variables. METHOD: The subjects were 33 male and 132
      female elderly inpatients certified to be at care level 4 or 5. The body
      composition included height, body weight, arm circumference, triceps skinfold
      thickness, subscapular skinfold thickness, calf circumference, and waist
      circumference. RESULTS: We studied the correlation between the body weight and
      each anthropometric variable and age. In men, the highest correlation with body
      weight was shown by waist circumference (r=0.891, p<0.0001), followed by age
      (r=0.779, p<0.0001) and calf circumference (r=0.614, p<0.0001). The variables
      that showed the highest correlation with body weight in women were waist
      circumference (r=0.806, p<0.0001), followed by triceps skinfold thickness
      (r=0.723, p<0.0001) and arm circumference (r=0.662, p<0.0001). The weight
      estimation formulae were obtained by multiple regression analysis. Formulae for
      men: body weight=0.660*waist circumference (cm)+0.702*calf circumference
      (cm)+0.096*age (years)-26.917 (R(2)=0.862, p<0.001); formulae for women: body
      weight=0.315*waist circumference (cm)+0.684*arm circumference (cm)+0.183*height
      (cm)-28.788 (R(2)=0.836, p<0.001). CONCLUSION: We successfully developed gender
      specific weight-estimation formulae with high coefficients of determination. The
      results suggest that waist circumference, which is an index of visceral fat, is
      an effective anthropometric variable to estimate the body weight of bedridden
      elderly patients requiring care.

PMID- 23883640
TI  - [Relationship between cognitive function and physical activities: a longitudinal
      study among community-dwelling elderly].
AB  - AIM: The purpose of this study was to evaluate whether physical activities reduce
      the risk of cognitive decline in community-dwelling elderly. We investigated
      correlations between cognitive functions at baseline and physical activities,
      correlations between cognitive functions at baseline and cognitive decline over 4
      years, as well as correlations between physical activity at baseline and
      cognitive decline over 4 years. METHODS: At baseline, 2,431 community-dwelling
      elderly completed the cognitive screening by telephone (TICS-J), and answered the
      questionnaires about physical activities. Of these, 1,040 subjects again
      completed the TICS-J over 4 years. Physical activities contained moving ability,
      walking frequency, walking speed, the exercise frequency. RESULTS: At baseline,
      870 elderly (age 75.87+/-4.96 (mean+/-SD) years, duration of education 11.05+/
      2.41) showed normal cognitive functions and 170 (79.19+/-6.22, 9.61+/-2.23)
      showed cognitive impairment. The total TICS-J score was significantly higher in
      cognitive normal subjects compared with that of cognitive impaired subjects
      (36.02+/-1.89, 30.19+/-2.25, respectively, p<0.001). Logistic regression analyses
      showed that moving ability significantly reduced the risk of cognitive impairment
      in an unadjusted model, and walking speed also reduced the risk of cognitive
      impairment at baseline even in an adjusted model. Cognitive function at baseline
      might be a predictor of cognitive function over 4 years. The longitudinal study
      revealed that walking speed and exercise frequency significantly correlate with
      maintenance of cognitive function over 4 years. CONCLUSIONS: This study provides
      that physical activities, especially walking speed have significant correlation
      with cognitive function.

PMID- 23883641
TI  - [Association between depression and fall risk among elderly community residents].
AB  - AIM: To investigate the relationship between depression and fall risk in the
      elderly. METHODS: Residents of a village in Kumamoto Prefecture, Japan (563
      people), aged >=65 years were given a self-administered questionnaire survey
      between June and July 2010. To evaluate depression status and fall risk, the
      Geriatric Depression Scale--Short Form and the Simple Screening Test for Risk of
      Falls were administered. Adjustment factors assessed were age, sex, medical
      history for diseases associated with falls, usage of hypnotics, and cognitive
      dysfunction. We examined the relationship between depression and fall risk using
      multiple logistic regression analysis. Given that some degree of correlation was
      expected among adjustment factors in the model, we constructed a model that
      introduced the adjustment factors stepwise to confirm the robustness of the model
      and any effect of multicollinearity. RESULTS: Overall (n=395), after excluding
      data from participants with significant cognitive disturbance or severe physical
      problems from among valid responders, a significant relationship was found
      between depression and fall risk in all models. The odds ratio was 2.28 (95%
      confidence interval: 1.31-3.96) in the final model, controlling for all
      adjustment factors. CONCLUSION: Our findings suggest a significant relationship
      between depression and fall risk in the elderly. This relationship implies that
      the improvement of depression could be an effective measure to decrease fall risk
      in the elderly.

PMID- 23883642
TI  - [Urinary bladder function in young and elderly women].
AB  - AIM: To identify the effect of aging on urinary bladder function, the maximal
      volume, post-voiding residual of the urinary bladder, mean urine flow rate, and
      urine volume were examined during micturition after drinking water (500-700 ml).
      METHODS: Bladder volume, post-voiding residual, mean urine flow rate, and urine
      volume during micturition were measured in young (22+/-3 yr, n=12) and elderly
      women (64+/-3 yr, n=6). RESULTS: The maximal urinary bladder volume was not
      significantly different (P>0.05) between young and elderly women (576+/-158 vs.
      505+/-119 ml). In contrast, post-voiding residual volume was greater (88+/-52 ml,
      P<0.05) in elderly than in 34+/-40 ml in young women. Accordingly, urine volume
      was decreased to 418+/-155 ml in elderly compared to the volume in young women
      (556+/-141 ml). Although mean urine flow rate of 16 ml/s was equivalent between
      young and elderly women, the time period necessary for voiding was 27+/-6 s in
      elderly women, shorter (p<0.05) than the period for 43+/-24 s in young women.
      CONCLUSION: It is suggested that contraction of the urinary bladder in elderly
      women is not so sustained as in young women, causing a greater post-voiding
      residual volume of the urinary bladder.

PMID- 23883643
TI  - [Nutrition support team (NST) intervention for hip fracture in elderly patients
      over 90 years old - Validation effect using the Functional Independence Measure].
AB  - AIM: Malnutrition is common in the hospitalized elderly with hip fractures and
      has been linked to poorer recovery and increased complications. Hence, the aim of
      this study is to investigate whether nutrition support team (NST) intervention
      has a beneficial effect on rehabilitation outcome in the elderly, especially in
      the oldest-old patients with hip fracture using the Functional Independence
      Measure (FIM). METHOD: Patients were classified into two groups before and after
      NST intervention, and we evaluated FIM gain, FIM efficacy, and discharge
      outcomes. Every item was compared in low-ADL patients with an FIM of 54 or less
      on admission. RESULTS: The numbers of patients were 18 in the non-NST and 22 in
      the NST group. Although nutritional indicators on admission showed no significant
      difference in the groups, FIM gain and FIM efficacy were significantly higher
      (p<0.01) and walking ability at discharge was better in the NST group (p<0.05).
      In low-ADL patients, the same results were confirmed. CONCLUSION: Although the
      malnourished patients often have a poor prognosis, there was a significant
      improvement in rehabilitation effect and discharge outcome in the NST group.
      Thus, these results suggest the effectiveness of multidisciplinary NST
      intervention. Moreover, even in elderly patients with low ADL on admission,
      significant effect of rehabilitation can be expected by appropriate nutritional
      management.

PMID- 23883644
TI  - [A case of intravascular large B-cell lymphoma with rapidly progressive cognitive
      impairment after cerebral infarction].
AB  - A 67-year-old man started to show symptoms of dementia and developed convulsions
      accompanied by presyncope. Since an old cerebral infarction was found, he was
      given a diagnosis of symptomatic epilepsy, treated with antiepileptics. Dementia
      progressed rapidly, resulting in admission to a dementia ward. There were no
      physical abnormalities, and only slight elevations of LDH and CRP were noted. He
      suddenly developed a fever between 38 degrees C and 39 degrees C. Only the serum
      concentration of soluble IL-2 receptor was elevated at 6,430 U/L. Although a
      malignant tumor of the lymphatic system was suspected, there was no swelling
      noted in the superficial lymph nodes. The patient suddenly developed hypoxemia,
      thrombocytopenia, and an increase in fibrin degradation products. Pulmonary
      thromboembolism was suspected, but contrast-enhanced chest CT did not reveal any
      abnormalities. Bone marrow aspiration did not detect any infiltrations of
      lymphoid cells but was suggestive of hemophagocytic syndrome. After that, a new
      cerebral infarction occurred. Based on the course, intravascular lymphoma, which
      causes microvascular occlusions in various organs, was considered probable.
      Prednisolone was administered at a dose of 60 mg daily and skin biopsy was
      scheduled. However, the patient experienced a sudden deterioration and died. In
      autopsy, immunostain with CD20 showed that the arteriolae, capillaries, and
      venulae of thoracic and abdominal organs were filled with cells of large B-cell
      lymphoma. The presence of similar cerebrovascular lesions was not confirmed, but
      can reasonably be speculated. Thus, the present case suggests that it is
      necessary to consider intravascular lymphoma when dementia rapidly progresses for
      unknown reasons. 

PMID- 23883645
TI  - [Japanese translation of "Sarcopenia: European consensus on definition and
      diagnosis: Report of the European Working Group on Sarcopenia in Older People"
      with supplementary explanation by the JGS working group].

PMID- 23883646
TI  - [Smell from elderly with dementia at end-of-life].

PMID- 23883648
TI  - We need theoretical physics approaches to study living systems.

PMID- 23883649
TI  - Acute sphenoid sinusitis leading to contralateral cavernous sinus thrombosis: a
      case report.
AB  - INTRODUCTION: The objective of this article was to report a case of isolated,
      acute, right-sided sphenoid sinusitis that progressed to contralateral cavernous
      sinus thrombosis in an 18-year-old male patient. We describe the atypical
      presentation of this case and discuss the relevant anatomy, pathogenesis,
      presentation, diagnostic evaluation and treatment. CASE REPORT: A case report of
      sphenoid sinusitis leading to contralateral cavernous sinus thrombosis was
      reviewed and presented along with a comprehensive literature review of the
      relevant anatomy, pathophysiology, microbiology, diagnostic work-up and treatment
      options. CONCLUSION: Cavernous sinus thrombosis is a rare clinical entity in the
      antibiotic era. However, limited sphenoid sinusitis may progress to cavernous
      sinus thrombosis in spite of maximal medical treatment, as highlighted in this
      case report. The mainstay of treatment includes early diagnosis allowing
      aggressive intravenous antibiotics and appropriate surgical management.

PMID- 23883650
TI  - Haemodilution is a mechanism of anaemia in patients with heart failure.

PMID- 23883651
TI  - Vagus nerve stimulation improves left ventricular function in a canine model of
      chronic heart failure.
AB  - AIMS: Autonomic dysfunction is a feature of chronic heart failure (HF). This
      study tested the hypothesis that chronic open-loop electrical vagus nerve
      stimulation (VNS) improves LV structure and function in canines with chronic HF.
      METHODS AND RESULTS: Twenty-six canines with HF (EF ~35%) produced by
      intracoronary microembolizations were implanted with a bipolar cuff electrode
      around the right cervical vagus nerve and connected to an implantable pulse
      generator. The canines were enrolled in Control (n = 7) vs. VNS therapy (n = 7)
      or a crossover study, with crossovers occurring at 3 months (C * VNS, n = 6; VNS
      * C, n = 6). After 6 months of VNS, LVEF and LV end-systolic volume (ESV) were
      significantly improved compared with Control (DeltaEF Control -4.6 +/- 0.9% vs.
      VNS 6.0 +/- 1.6%, P < 0.001) and (DeltaESV Control 8.3 +/- 1.8 mL vs. VNS -3.0 +/
      2.3 mL, P = 0.002. Plasma and tissue biomarkers were also improved. In the
      crossover study, VNS also resulted in a significant improvement in EF and ESV
      compared with Control (DeltaEF Control -2.3 +/- 0.65% vs. VNS 6.7 +/- 1.1 mL, P <
      0.001 and DeltaESV Control 3.2 +/- 1.2 mL vs. VNS -4.0 +/- 0.9 mL, P < 0.001).
      Initiation of therapy in the Control group at 3 months resulted in a significant
      improvement in EF (Control -4.7 +/- 1.4% vs. VNS 3.7 +/- 0.74%, P < 0.001) and
      ESV (Control 1.5 +/- 1.2 mL vs. NS -5.5 +/- 1.6 mL, P = 0.003) by 6 months.
      CONCLUSIONS: In canines with HF, long-term, open-looped low levels of VNS therapy
      improves LV systolic function, prevents progressive LV enlargement, and improves
      biomarkers of HF when compared with control animals that did not receive therapy.

PMID- 23883652
TI  - Hyponatraemia predicts the acute (type 1) cardio-renal syndrome.
AB  - AIMS: The acute (type 1) cardio-renal syndrome (CRS) refers to an acute worsening
      of heart function leading to worsening renal function (WRF), and frequently
      complicates acute decompensated heart failure (ADHF) and acute myocardial
      infarction (AMI). The aim of this study was to investigate whether hyponatraemia,
      a surrogate marker of congestion and haemodilution and of neurohormonal
      activation, could identify patients at risk for WRF. METHODS AND RESULTS: We
      studied the association between hyponatraemia (sodium <136 mmol/L) and WRF
      (defined as an increase of >0.3 mg/dL in creatinine above baseline) in two
      separate cohorts: patients with ADHF (n = 525) and patients with AMI (n = 2576).
      Hyponatraemia on admission was present in 156 patients (19.7%) with ADHF and 461
      patients (17.7%) with AMI. Hyponatraemia was more frequent in patients who
      subsequently developed WRF as compared with patients who did not, in both the
      ADHF (34.6% vs. 22.2%, P = 0.0003) and AMI (29.7% vs. 21.8%, P<0.01) cohorts. In
      a multivariable logistic regression model, the multivariable adjusted odds ratio
      for WRF was 1.90 [95% confidence interval (CI) 1.25-2.88; P = 0.003] and 1.56
      (95% CI 1.13-2.16; P = 0.002) in the ADHF and AMI cohorts, respectively. The
      mortality risk associated with hyponatraemia was attenuated in the absence of
      WRF. CONCLUSION: Hyponatraemia predicts the development of WRF in two clinical
      scenarios that frequently lead to the type I CRS. These data are consistent with
      the concept that congestion and neurohormonal activation play a pivotal role in
      the pathophysiology of acute cardio-renal failure.

PMID- 23883653
TI  - Renal denervation in heart failure with normal left ventricular ejection
      fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl
      Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial.
AB  - Aim Increasing evidence suggests an important role for hyperactivation of the
      sympathetic nervous system (SNS) in the clinical phenomena of heart failure with
      normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic
      activation is directly related to the severity of heart failure. Since
      percutaneous renal denervation (pRDN) has been shown to be effective in
      modulating elevated SNS activity in patients with hypertension, it can be
      hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will
      investigate whether renal sympathetic denervation influences parameters of HFNEF.
      Methods DIASTOLE is a multicentre, randomized controlled trial. Sixty patients,
      diagnosed with HFNEF and treated for hypertension, will be randomly allocated in
      a 1:1 ratio to undergo renal denervation on top of medical treatment (n = 30) or
      to maintain medical treatment alone (n = 30). The primary objective is to
      investigate the efficacy of pRDN by means of pulsed wave Doppler
      echocardiographic parameters. Secondary objectives include safety of pRDN and a
      comparison of changes in the following parameters after pRDN: LV mass, LV volume,
      LVEF, and left atrial volume as determined by magnetic resonance imaging. Also,
      MIBG (metaiodobenzylguanidine) uptake and washout, BNP levels, blood pressure,
      heart rate variability, exercise capacity, and quality of life will be assessed.
      Perspective DIASTOLE is a randomized controlled trial evaluating renal
      denervation as a treatment option for HFNEF. The results of the current trial
      will provide important information regarding the treatment of HFNEF, and
      therefore may have major impact on future therapeutic strategies. Trail
      registration NCT01583881. 

PMID- 23883654
TI  - The changing face of heart failure: are we really making progress?

PMID- 23883655
TI  - Heart failure in elderly patients: it is time to add geriatric assessment.

PMID- 23883656
TI  - Temporal trends in prevalence of CKD: the glass is half full and not half empty.

PMID- 23883657
TI  - Loss of kidney function with aging is a patient safety hazard.

PMID- 23883658
TI  - Death, taxes, and now CKD.

PMID- 23883659
TI  - Canadian hemodialysis patients in rural dwellings: reflections on quality of care
      indicators.

PMID- 23883660
TI  - Overestimation of life expectancy in CKD.

PMID- 23883661
TI  - In reply to 'Overestimation of life expectancy in CKD'.

PMID- 23883662
TI  - Kidney failure in a transplant from an identical twin.

PMID- 23883664
TI  - The k-space origins of scattering in Bi2Sr2CaCu2O8+x.
AB  - We demonstrate a general, computer automated procedure that inverts the
      reciprocal space scattering data (q-space) that are measured by spectroscopic
      imaging scanning tunnelling microscopy (SI-STM) in order to determine the
      momentum space (k-space) scattering structure. This allows a detailed examination
      of the k-space origins of the quasiparticle interference (QPI) pattern in
      Bi2Sr2CaCu2O8+x within the theoretical constraints of the joint density of states
      (JDOS). Our new method allows measurement of the differences between the positive
      and negative energy dispersions, the gap structure and an energy dependent
      scattering length scale. Furthermore, it resolves the transition between the
      dispersive QPI and the checkerboard ([Formula: see text] excitation). We have
      measured the k-space scattering structure over a wide range of doping (p ~ 0.22
      0.08), including regions where the octet model is not applicable. Our technique
      allows the complete mapping of the k-space scattering origins of the spatial
      excitations in Bi2Sr2CaCu2O8+x, which allows for better comparisons between SI
      STM and other experimental probes of the band structure. By applying our new
      technique to such a heavily studied compound, we can validate our new general
      approach for determining the k-space scattering origins from SI-STM data. 

PMID- 23883663
TI  - Effectiveness and cost-effectiveness of measuring fecal calprotectin in diagnosis
      of inflammatory bowel disease in adults and children.
AB  - BACKGROUND & AIMS: The level of fecal calprotectin (FC) can predict the onset of
      inflammatory bowel disease (IBD) with high accuracy and precision. We evaluated
      the cost-effectiveness of using measurements of FC to identify adults and
      children who require endoscopic confirmation of IBD. METHODS: We constructed a
      decision analytic tree to compare the cost-effectiveness of measuring FC before
      endoscopy examination with that of direct endoscopic evaluation alone. A second
      decision analytic tree was constructed to evaluate the cost-effectiveness of FC
      cutoff levels of 100 MUg/g vs 50 MUg/g (typically used to screen for intestinal
      inflammation). The primary outcome measure was the incremental cost required to
      avoid 1 false-negative result by using FC level to diagnose new-onset IBD.
      RESULTS: In adults, FC screening saved $417/patient but delayed diagnosis for
      2.2/32 patients with IBD among 100 screened patients. In children, FC screening
      saved $300/patient but delayed diagnosis for 4.8/61 patients with IBD among 100
      screened patients. If endoscopic biopsy analysis remained the standard for
      diagnosis, direct endoscopic evaluation would cost an additional $18,955 in
      adults and $6250 in children to avoid 1 false-negative result from FC screening.
      Sensitivity analyses showed that cost-effectiveness of FC screening varied with
      the sensitivity of the test and the pre-test probability of IBD in adults and
      children. Pre-test probabilities for IBD of <=75% in adults and <=65% in children
      made FC screening cost-effective, but it was cost-ineffective if the
      probabilities were >=85% and >=78% in adults and children, respectively. Compared
      with the FC cutoff level of 100 MUg/g, the cutoff level of 50 MUg/g cost an
      additional $55 and $43 for adults and children, respectively, but it yielded 2.4
      and 6.1 additional accurate diagnoses of IBD per 100 screened adults and
      children, respectively. CONCLUSIONS: Screening adults and children to measure
      fecal levels of calprotectin is effective and cost-effective in identifying those
      with IBD on a per-case basis when the pre-test probability is <=75% for adults
      and <=65% for children. The utility of the test is greater for adults than
      children. Increasing the FC cutoff level to >=50 MUg/g increases diagnostic
      accuracy without substantially increasing total cost.

PMID- 23883665
TI  - Granulomatous rhinitis due to Candida parapsilosis in a cat.
AB  - A 9-year-old female spayed Domestic Medium Hair cat presented to the referring
      veterinarian with a 2-week history of sneezing, which progressed to swelling over
      the nasal planum. The cat had been under veterinary care for inflammatory bowel
      disease and had been treated with 1.25 mg/kg prednisolone once a day for
      approximately 1 year. On physical examination, an approximately 2-3 mm diameter,
      round polypoid pink soft-tissue mass was protruding slightly from the right
      nostril. Through histologic examination of representative sections from the mass,
      there was a severe diffuse infiltrate of epithelioid macrophages and neutrophils
      that surrounded frequent 15-20 um yeast organisms. A Grocott methenamine silver
      stain revealed the presence of pseudohyphae in addition to the previously noted
      yeast forms. Real-time polymerase chain reaction (PCR) for Cryptococcus
      neoformans, Ajellomyces dermatitidis (syn. Blastomyces dermatitidis),
      Coccidioides immitis, Ajellomyces capsulatus (syn. Histoplasma capsulatum),
      Malassezia spp., and Candida spp. was performed on the paraffin-embedded sample.
      The PCR for Candida spp. was positive; the product was then sequenced and was
      determined to be consistent with Candida parapsilosis. Following the PCR
      diagnosis and prior to treatment of the infection, C. parapsilosis was cultured
      from a nasal swab. The infection in the cat in the current report was considered
      opportunistic and secondary to immunosuppression, following treatment for the
      inflammatory bowel disease. 

PMID- 23883666
TI  - Vesicular stomatitis outbreak in the southwestern United States, 2012.
AB  - Vesicular stomatitis is a viral disease primarily affecting horses and cattle
      when it occurs in the United States. Outbreaks in the southwestern United States
      occur sporadically, with initial cases typically occurring in Texas, New Mexico,
      or Arizona and subsequent cases occurring in a northward progression. The viruses
      causing vesicular stomatitis can be transmitted by direct contact of lesioned
      animals with other susceptible animals, but transmission is primarily through
      arthropod vectors. In 2012, an outbreak of vesicular stomatitis in the United
      States occurred that was caused by Vesicular stomatitis New Jersey virus
      serotype. Overall, 51 horses on 36 premises in 2 states were confirmed positive.
      Phylogenetic analysis of the virus indicated that it was most closely related to
      viruses detected in the state of Veracruz, Mexico, in 2000. 

PMID- 23883668
TI  - Insight, positive and negative symptoms, hope, depression and self-stigma: a
      comprehensive model of mutual influences in schizophrenia spectrum disorders.
AB  - Aims. Insight, positive and negative symptoms, hope, depression and self-stigma
      are relevant variables in schizophrenia spectrum disorders. So far, research on
      their mutual influences has been patchy. This study simultaneously tests the
      associations between these variables. Methods. A total of 284 people with
      schizophrenia spectrum disorders were assessed using the Schedule for the
      Assessment of Insight, Positive and Negative Syndrome Scale, Integrative Hope
      Scale, Centre for Epidemiological Studies Depression Scale and Internalized
      Stigma of Mental Illness scale. Path analysis was applied to test the
      hypothesized relationships between the variables. Results. Model support was
      excellent. Strong and mutual causal influences were confirmed between hope,
      depression and self-stigma. The model supported the assumption that insight
      diminishes hope and increases depression and self-stigma. While negative symptoms
      directly affected these three variables, reducing hope and increasing depression
      and self-stigma, positive symptoms did not. However, positive symptoms diminished
      self-stigma on a pathway via insight. Conclusions. This study provides a
      comprehensive synopsis of the relationships between six variables relevant for
      schizophrenia spectrum disorders. Research implications include the need to
      investigate determinants of consequences of insight, and the sequence of
      influences exerted by positive and negative symptoms. Clinical implications
      include the importance of interventions against self-stigma and of taking a
      contextualized approach to insight. 

PMID- 23883667
TI  - beta1-Integrin via NF-kappaB signaling is essential for acquisition of
      invasiveness in a model of radiation treated in situ breast cancer.
AB  - INTRODUCTION: Ductal carcinoma in situ (DCIS) is characterized by non-invasive
      cancerous cell growth within the breast ducts. Although radiotherapy is commonly
      used in the treatment of DCIS, the effect and molecular mechanism of ionizing
      radiation (IR) on DCIS are not well understood, and invasive recurrence following
      radiotherapy remains a significant clinical problem. This study investigated the
      effects of IR on a clinically relevant model of Akt-driven DCIS and identified
      possible molecular mechanisms underlying invasive progression in surviving cells.
      METHODS: We measured the level of phosphorylated-Akt (p-Akt) in a cohort of human
      DCIS specimens by immunohistochemistry (IHC) and correlated it with recurrence
      risk. To model human DCIS, we used Akt overexpressing human mammary epithelial
      cells (MCF10A-Akt) which, in three-dimensional laminin-rich extracellular matrix
      (lrECM) and in vivo, form organotypic DCIS-like lesions with lumina expanded by
      pleiomorphic cells contained within an intact basement membrane. In a population
      of cells that survived significant IR doses in three-dimensional lrECM, a
      malignant phenotype emerged creating a model for invasive recurrence. RESULTS: P
      Akt was up-regulated in clinical DCIS specimens and was associated with recurrent
      disease. MCF10A-Akt cells that formed DCIS-like structures in three-dimensional
      lrECM showed significant apoptosis after IR, preferentially in the luminal
      compartment. Strikingly, when cells that survived IR were repropagated in three
      dimensional lrECM, a malignant phenotype emerged, characterized by invasive
      activity, up-regulation of fibronectin, alpha5beta1-integrin, matrix
      metalloproteinase-9 (MMP-9) and loss of E-cadherin. In addition, IR induced
      nuclear translocation and binding of nuclear factor-kappa B (NF-kappaB) to the
      beta1-integrin promoter region, associated with up-regulation of alpha5beta1
      integrins. Inhibition of NF-kappaB or beta1-integrin signaling abrogated
      emergence of the invasive activity. CONCLUSIONS: P-Akt is up-regulated in some
      human DCIS lesions and is possibly associated with recurrence. MCF10A-Akt cells
      form organotypic DCIS-like lesions in three-dimensional lrECM and in vivo, and
      are a plausible model for some forms of human DCIS. A population of Akt-driven
      DCIS-like spheroids that survive IR progresses to an invasive phenotype in three
      dimensional lrECM mediated by beta1-integrin and NF-kappaB signaling.

PMID- 23883670
TI  - Effect of ribosome shielding on mRNA stability.
AB  - Based on the experimental evidence that translating ribosomes stabilize the
      mRNAs, we introduce and study a theoretical model for the dynamic shielding of
      mRNA by ribosomes. We present an improved fitting of published decay assay data
      in E. coli and show that only one third of the decay patterns are exponential.
      Our new transcriptome-wide estimate of the average lifetimes and mRNA half-lives
      shows that these timescales are considerably shorter than previous estimates. We
      also explain why there is a negative correlation between mRNA length and average
      lifetime when the mRNAs are subdivided in classes sharing the same degradation
      parameters. As a by-product, our model indicates that co-transcriptional
      translation in E. coli may be less common than previously believed. 

PMID- 23883669
TI  - Extracranial glioblastoma with synchronous metastases in the lung, pulmonary
      lymph nodes, vertebrae, cervical muscles and epidural space in a young patient -
      case report and review of literature.
AB  - BACKGROUND: Extraneural and extracranial metastases of glioblastoma (GB) are very
      rarely reported in the literature. They occur in only 0.2% of all GB patients.
      CASE PRESENTATION: We present a 40 year old caucasian male with secondary GB and
      first diagnosis of an astrocytoma world health organisation (WHO) grade II
      through stereotactic biopsy in 2006. He presented a new hemiparesis and a
      progress of the known mass lesion in 2008. Subtotal tumor resection was performed
      and the histological examination verified a GB. After combined radio- and
      chemotherapy the adjuvant temozolomide therapy was not started because of non
      compliance. In 2011 a second local relapse was resected and 4 month later the
      patient presented a fast progressing tetraparesis. Cervical CT and MRI scan
      showed a mass lesion infiltrating the fifth and sixth vertebra with infiltration
      of the spinal canal and large paravertebral tumor masses. Emergency surgery was
      performed. By additional screening further metastases were detected in the
      thoracal and lumbal spine and surprisingly also in the lung and pulmonary
      lymphnodes. Palliative radio- and chemotherapy of the pulmonal lesions was
      completed, further antitumor therapy was rejected. The patient died 10 months
      after diagnosis of the extraneural metastases. CONCLUSION: Especially young "long
      term-survivors" seem to have a higher risk of extraneural metastasis from a GB
      and appropriate staging should be performed in these cases.

PMID- 23883671
TI  - Whole body heat loss is reduced in older males during short bouts of intermittent
      exercise.
AB  - Studies in young adults show that a greater proportion of heat is gained shortly
      following the start of exercise and that temporal changes in whole body heat loss
      during intermittent exercise have a pronounced effect on body heat storage. The
      consequences of short-duration intermittent exercise on heat storage with aging
      are unclear. We compared evaporative heat loss (HE) and changes in body heat
      content (DeltaHb) between young (20-30 yr), middle-aged (40-45 yr), and older
      males (60-70 yr) of similar body mass and surface area, during successive
      exercise (4 * 15 min) and recovery periods (4 * 15 min) at a fixed rate of heat
      production (400 W) and under fixed environmental conditions (35  degrees C/20%
      relative humidity). HE was lower in older males vs. young males during each
      exercise (Ex1: 283 +/- 10 vs. 332 +/- 11 kJ, Ex2: 334 +/- 10 vs. 379 +/- 5 kJ,
      Ex3: 347 +/- 11 vs. 392 +/- 5 kJ, and Ex4: 347 +/- 10 vs. 387 +/- 5 kJ, all P <
      0.02), whereas HE in middle-aged males was intermediate to that measured in young
      and older adults (Ex1: 314 +/- 13, Ex2: 355 +/- 13, Ex3: 371 +/- 13, and Ex4: 365
      +/- 8 kJ). HE was not significantly different between groups during the recovery
      periods. The net effect over 2 h was a greater DeltaHb in older (267 +/- 33 kJ; P
      = 0.016) and middle-aged adults (245 +/- 16 kJ; P = 0.073) relative to younger
      counterparts (164 +/- 20 kJ). As a result of a reduced capacity to dissipate heat
      during exercise, which was not compensated by a sufficiently greater rate of heat
      loss during recovery, both older and middle-aged males had a progressively
      greater rate of heat storage compared with young males over 2 h of intermittent
      exercise.

PMID- 23883672
TI  - Increased ventricular stiffness and decreased cardiac function in Atlantic cod
      (Gadus morhua) at high temperatures.
AB  - We employed the work loop method to study the ability of ventricular and atrial
      trabeculae from Atlantic cod to sustain power production during repeated
      contractions at acclimation temperatures (10 degrees C) and when acutely warmed
      (20 degrees C). Oxygen tension (Po2) was lowered from 450 to 34% air saturation
      to augment the thermal stress. Preparations worked under conditions simulating
      either a large stroke volume (35 contractions/min rate, 8-12% muscle strain) or a
      high heart rate (70 contractions/min, 2-4% strain), with power initially equal
      under both conditions. The effect of declining Po2 on power was similar under
      both conditions but was temperature and tissue dependent. In ventricular
      trabeculae at 10 degrees C (and atria at 20 degrees C), shortening power declined
      across the full range of Po2 studied, whereas the power required to lengthen the
      muscle was unaffected. Conversely, in ventricular trabeculae at 20 degrees C,
      there was no decline in shortening power but an increase in lengthening power
      when Po2 fell below 100% air saturation. Finally, when ventricular trabeculae
      were paced at rates of up to 115 contractions/min at 20 degrees C (vs. the
      maximum of 70 contractions/min in vivo), they showed marked increases in both
      shortening and lengthening power. Our results suggest that although elevated
      heart rates may not impair ventricular power as they commonly do isometric force,
      limited atrial power and the increased work required to expand the ventricle
      during diastole may compromise ventricular filling and hence, stroke volume in
      Atlantic cod at warm temperatures. Neither large strains nor high contraction
      rates convey an apparent advantage in circumventing this. 

PMID- 23883673
TI  - The emerging role of relaxin as a novel therapeutic pathway in the treatment of
      chronic kidney disease.
AB  - Emerging evidence supports a potential therapeutic role of relaxin in fibrotic
      diseases, including chronic kidney disease. Relaxin is a pleiotropic hormone,
      best characterized for its role in the reproductive system; however, recent
      studies have demonstrated a role of relaxin in the cardiorenal system. Both
      relaxin and its receptor, RXFP1, are expressed in the kidney, and relaxin has
      been shown to play a role in renal vasodilation, in sodium excretion, and as an
      antifibrotic agent. Together, these findings suggest that the kidney is a target
      organ of relaxin. Therefore, the purpose of this review is to describe the
      functional and structural impacts of relaxin treatment on the kidney and to
      discuss evidence that relaxin prevents disease progression in several
      experimental models of kidney disease. In addition, this review will present
      potential mechanisms that are involved in the therapeutic actions of relaxin. 

PMID- 23883675
TI  - Effects of an intensive short-term diet and exercise intervention: comparison
      between normal-weight and obese children.
AB  - Lifestyle intervention programs currently emphasize weight loss secondary to
      obesity as the primary determinant of phenotypic changes. We examined whether the
      effects of a short-term lifestyle intervention program differ in normal-weight
      versus overweight/obese children. Nineteen overweight/obese (O; BMI = 33.6 +/-
      1.9 kg/m(2)) and 14 normal-weight (N; BMI = 19.9 +/- 1.5 kg/m(2)) children
      participated in a 2-wk program consisting of an ad libitum high-fiber, low-fat
      diet and daily exercise (2-2.5 h). Fasting serum samples were taken pre- and
      postintervention for determination of lipids, glucose homeostasis, inflammatory
      cytokines, and adipokines. Only the O group lost weight (3.9%) but remained
      overweight/obese (32.3 +/- 1.9 kg/m(2)). Both groups exhibited significant
      intervention-induced decreases (P < 0.05) in serum insulin (N: 52.5% vs. O:
      28.1%; between groups, P = 0.38), homeostatic model assessment for insulin
      resistance (N: 53.1% vs. O: 28.4%, P = 0.43), leptin (N: 69.3% vs. O: 44.1%, P =
      0.10), amylin (N: 28.7% vs. O: 26.1%, P = 0.80), resistin (N: 40.0% vs. O: 35.1%,
      P = 0.99), plasminogen activator-inhibitor-1 (N: 30.8% vs. O: 25.6%, P = 0.59),
      IL-6 (N: 58.8% vs. O: 48.5%, P = 0.78), IL-8 (N: 46.0% vs. O: 42.2%, P = 0.49),
      and TNFalpha (N: 45.8% vs. O: 40.8%, P = 0.99). No associations between indices
      of weight change and phenotypic changes were noted. A short-term, intensive
      lifestyle modification program is effective in ameliorating metabolic risk
      factors in N and O children. These results suggest that obesity per se was not
      the primary driver of the phenotypes noted and that dietary intake and physical
      inactivity induce the phenotypic abnormalities. These data may have implications
      for the weight loss-independent management of cardiometabolic risk in pediatric
      populations. 

PMID- 23883674
TI  - Selective leptin resistance revisited.
AB  - In addition to effects on appetite and metabolism, leptin influences many
      neuroendocrine and physiological systems, including the sympathetic nervous
      system. Building on my Carl Ludwig Lecture of the American Physiological Society,
      I review the sympathetic and cardiovascular actions of leptin. The review focuses
      on a critical analysis of the concept of selective leptin resistance (SLR) and
      the role of leptin in the pathogenesis of obesity-induced hypertension in both
      experimental animals and humans. We introduced the concept of SLR in 2002 to
      explain how leptin might increase blood pressure (BP) in obese states, such as
      diet-induced obesity (DIO), that are accompanied by partial leptin resistance.
      This concept, analogous to selective insulin resistance in the metabolic
      syndrome, holds that in several genetic and acquired models of obesity, there is
      preservation of the renal sympathetic and pressor actions of leptin despite
      attenuation of the appetite and weight-reducing actions. Two potential
      overlapping mechanisms of SLR are reviewed: 1) differential leptin molecular
      signaling pathways that mediate selective as opposed to universal leptin action
      and 2) brain site-specific leptin action and resistance. Although the phenomenon
      of SLR in DIO has so far focused on preservation of sympathetic and BP actions of
      leptin, consideration should be given to the possibility that this concept may
      extend to preservation of other actions of leptin. Finally, I review perplexing
      data on the effects of leptin on sympathetic activity and BP in humans and its
      role in human obesity-induced hypertension. 

PMID- 23883676
TI  - Sex differences in angiotensin II- and aldosterone-induced hypertension: the
      central protective effects of estrogen.
AB  - Premenopausal women have lower blood pressure and a reduced incidence of
      cardiovascular disease compared with age-matched men. Similar sex differences
      have been seen across species and in multiple animal models of hypertension.
      While important progress over the last decade has been made in elucidating some
      of the mechanisms underlying these differences, there are still significant gaps
      in our knowledge. Understanding the cellular and molecular mechanisms responsible
      for sex differences in hypertension will be important for developing sex-specific
      therapies targeted toward the prevention and treatment of hypertension. Female
      sex hormones, especially estrogen, have been demonstrated to modulate the renin
      angiotensin-aldosterone system (RAAS) and to have beneficial effects on
      cardiovascular function through actions not only on the kidney, heart, and
      vasculature, but also on the central nervous system (CNS). This review primarily
      focuses on the central regulatory actions of estrogen on brain nuclei involved in
      blood pressure regulation and the interactions between estrogen and the RAAS in
      the CNS by which estrogen plays an important protective role against the
      development of hypertension. 

PMID- 23883677
TI  - The autonomic effects of cardiopulmonary decompression sickness in swine using
      principal dynamic mode analysis.
AB  - Methods to predict onset of cardiopulmonary (CP) decompression sickness (DCS)
      would be of great benefit to clinicians caring for stricken divers. Principal
      dynamic mode (PDM) analysis of the electrocardiogram has been shown to provide
      accurate separation of the sympathetic and parasympathetic tone dynamics. Nine
      swine (Sus scrofa) underwent a 15-h saturation dive at 184 kPa (60 ft. of
      saltwater) in a hyperbaric chamber followed by dropout decompression, whereas six
      swine, used as a control, underwent a 15-h saturation dive at 15 kPa (5 ft. of
      saltwater). Noninvasive electrocardiograms were recorded throughout the
      experiment and autonomic nervous system dynamics were evaluated by heart rate
      series analysis using power spectral density (PSD) and PDM methods. We observed a
      significant increase in the sympathetic and parasympathetic tones using the PDM
      method on average 20 min before DCS onset following a sudden induction of
      decompression. Parasympathetic activities remained elevated, but the sympathetic
      modulation was significantly reduced at onset of cutis and CP DCS signs, as
      reported by a trained observer. Similar nonsignificant observations occurred
      during PSD analysis. PDM observations contrast with previous work showing that
      neurological DCS resulted in a >50% reduction in both sympathetic and
      parasympathetic tone. Therefore, tracking dynamics of the parasympathetic tones
      via the PDM method may allow discrimination between CP DCS and neurological DCS,
      and this significant increase in parasympathetic tone has potential use as a
      marker for early diagnosis of CP DCS.

PMID- 23883679
TI  - Female SHR have greater blood pressure sensitivity and renal T cell infiltration
      following chronic NOS inhibition than males.
AB  - Nitric oxide is a critical regulator of blood pressure (BP) and inflammation, and
      female spontaneously hypertensive rats (SHR) have higher renal nitric oxide
      bioavailability than males. We hypothesize that female SHR will have a greater
      rise in BP and renal T cell infiltration in response to nitric oxide synthase
      (NOS) inhibition than males. Both male and female SHR displayed a dose-dependent
      increase in BP to the nonspecific NOS inhibitor N(G)-nitro-L-arginine methyl
      ester (L-NAME: 2, 5, and 7 mg.kg(-1).day(-1) for 4 days each); however, females
      exhibited a greater increase in BP than males. Treatment of male and female SHR
      with 7 mg.kg(-1).day(-1) L-NAME for 2 wk significantly increased BP in both
      sexes; however, prior exposure to L-NAME only increased BP sensitivity to chronic
      NOS inhibition in females. L-NAME-induced hypertension increased renal T cell
      infiltration and indices of renal injury in both sexes, yet female SHR exhibited
      greater increases in Th17 cells and greater decreases in regulatory T cells than
      males. Chronic L-NAME was also associated with larger increases in renal cortical
      adhesion molecule expression in female SHR. The use of triple therapy to block L
      NAME-mediated increases in BP attenuated L-NAME-induced increases in renal T cell
      counts and normalized adhesion molecule expression in SHR, suggesting that L-NAME
      induced increases in renal T cells were dependent on both increases in BP and NOS
      inhibition. Our data suggest that NOS is critical in the ability of SHR, females
      in particular, to maintain BP and limit a pro-inflammatory renal T cell profile.

PMID- 23883678
TI  - Integration of thermal and osmotic regulation of water homeostasis: the role of
      TRPV channels.
AB  - Maintenance of body water homeostasis is critical for preventing hyperthermia,
      because evaporative cooling is the most efficient means of dissipating excess
      body heat. Water homeostasis is achieved by regulation of water intake and water
      loss by the kidneys. The former is achieved by sensations of thirst that motivate
      water acquisition, whereas the latter is regulated by the antidiuretic action of
      vasopressin. Vasopressin secretion and thirst are stimulated by increases in the
      osmolality of the extracellular fluid as well as decreases in blood pressure
      and/or blood volume, signals that are precipitated by water depletion associated
      with the excess evaporative water loss required to prevent hyperthermia. In
      addition, they are stimulated by increases in body temperature. The sites and
      molecular mechanisms involved in integrating thermal and osmotic regulation of
      thirst and vasopressin secretion are reviewed here with a focus on the role of
      the thermal and mechanosensitive transient receptor potential-vanilloid (TRPV)
      family of ion channels.

PMID- 23883681
TI  - In vivo imaging of intracellular Ca2+ after muscle contractions and direct Ca2+
      injection in rat skeletal muscle in diabetes.
AB  - The effects of muscle contractions on the profile of postcontraction resting
      intracellular Ca2+ ([Ca2+]i) accumulation in Type 1 diabetes are unclear. We
      tested the hypothesis that, following repeated bouts of muscle contractions, the
      rise in resting [Ca2+]i evident in healthy rats would be increased in diabetic
      rats and that these changes would be associated with a decreased cytoplasmic Ca2+
      -buffering capacity. Adult male Wistar rats were divided randomly into diabetic
      (DIA; streptozotocin, ip) and healthy control (CONT) groups. Four weeks later,
      animals were anesthetized and spinotrapezius muscle contractions (10 sets of 50
      contractions) were elicited by electrical stimulation (100 Hz). Ca2+ imaging was
      achieved using Fura-2 AM in the spinotrapezius muscle in vivo (i.e., circulation
      intact). The ratio (340/380 nm) was determined from fluorescence images following
      each set of contractions for estimation of [Ca2+]i. Also, muscle Ca2+ buffering
      was studied in individual myocytes microinjected with 2 mM Ca2+ solution. After
      muscle contractions, resting [Ca2+]i in DIA increased earlier and more rapidly
      than in CONT (P < 0.05 vs. precontraction). Peak [Ca2+]i in response to the Ca2+
      injection was significantly higher in CONT (25.8 +/- 6.0% above baseline) than
      DIA (10.2 +/- 1.1% above baseline). Subsequently, CONT [Ca(2+)]i decreased
      rapidly (<15 s) to plateau 9-10% above baseline, whereas DIA remained elevated
      throughout the 60-s measurement window. No differences in SERCA1 and SERCA2 (Ca2+
      uptake) protein levels were evident between CONT and DIA, whereas ryanodine
      receptor (Ca2+ release) protein level and mitochondrial oxidative enzyme activity
      (succinate dehydrogenase) were decreased in DIA (P < 0.05). In conclusion,
      diabetes impairs resting [Ca2+]i homeostasis following muscle contractions.
      Markedly different responses to Ca2+ injection in DIA vs. CONT suggest
      fundamentally deranged Ca2+ handling.

PMID- 23883680
TI  - High-protein diet selectively reduces fat mass and improves glucose tolerance in
      Western-type diet-induced obese rats.
AB  - Obesity is an increasing health problem. Because drug treatments are limited,
      diets remain popular. High-protein diets (HPD) reduce body weight (BW), although
      the mechanisms are unclear. We investigated physiological mechanisms altered by
      switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD.
      Male rats were fed standard (SD) or WTD (45% calories from fat). After developing
      DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD
      (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body
      composition, glucose tolerance, insulin sensitivity, and intestinal hormone
      plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25%
      greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats
      switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9
      (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05).
      During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05),
      whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD
      at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide
      and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared
      with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats,
      which may be related to decreased FI and the selective reduction of fat mass
      accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in
      the treatment of obesity. 

PMID- 23883682
TI  - Effect of intensified training on muscle ion kinetics, fatigue development, and
      repeated short-term performance in endurance-trained cyclists.
AB  - The effects of intensified training in combination with a reduced training volume
      on muscle ion kinetics, transporters, and work capacity were examined. Eight well
      trained cyclists replaced their regular training with speed-endurance training
      (12 * 30 s sprints) 2-3 times per week and aerobic high-intensity training (4-5 *
      3-4 min at 90-100% of maximal heart rate) 1-2 times per week for 7 wk and reduced
      training volume by 70% (intervention period; IP). The duration of an intense
      exhaustive cycling bout (EX2; 368 +/- 6 W), performed 2.5 min after a 2-min
      intense cycle bout (EX1), was longer (P < 0.05) after than before IP (4:16 +/-
      0:34 vs. 3:37 +/- 0:28 min:s), and mean and peak power during a repeated sprint
      test improved (P < 0.05) by 4% and 3%, respectively. Femoral venous K(+)
      concentration in recovery from EX1 and EX2 was lowered (P < 0.05) after compared
      with before IP, whereas muscle interstitial K(+) concentration and net muscle
      K(+) release during exercise was unaltered. No changes in muscle lactate and H(+)
      release during and after EX1 and EX2 were observed, but the in vivo buffer
      capacity was higher (P < 0.05) after IP. Expression of the ATP-sensitive K(+)
      (KATP) channel (Kir6.2) decreased by IP, with no change in the strong inward
      rectifying K(+) channel (Kir2.1), muscle Na(+)-K(+) pump subunits,
      monocarboxylate transporters 1 and 4 (MCT1 and MCT4), and Na(+)/H(+) exchanger 1
      (NHE1). In conclusion, 7 wk of intensified training with a reduced training
      volume improved performance during repeated intense exercise, which was
      associated with a greater muscle reuptake of K(+) and muscle buffer capacity but
      not with the amount of muscle ion transporters.

PMID- 23883683
TI  - Pupillary reflex measurement predicts insufficient analgesia before endotracheal
      suctioning in critically ill patients.
AB  - INTRODUCTION: This study aimed to evaluate the pupillary dilatation reflex (PDR)
      during a tetanic stimulation to predict insufficient analgesia before nociceptive
      stimulation in the intensive care unit (ICU). METHODS: In this prospective non
      interventional study in a surgical ICU of a university hospital, PDR was assessed
      during tetanic stimulation (of 10, 20 or 40 mA) immediately before 40
      endotracheal suctionings in 34 deeply sedated patients. An insufficient analgesia
      during endotracheal suction was defined by an increase of >=1 point on the
      Behavioral Pain Scale (BPS). RESULTS: A total of 27 (68%) patients had
      insufficient analgesia. PDR with 10 mA, 20 mA and 40 mA stimulation was higher in
      patients with insufficient analgesia (P <0.01). The threshold values of the pupil
      diameter variation during a 10, 20 and 40 mA tetanic stimulation to predict
      insufficient analgesia during an endotracheal suctioning were 1, 5 and 13%
      respectively. The areas (95% confidence interval) under the receiver operating
      curve were 0.70 (0.54 to 0.85), 0.78 (0.61 to 0.91) and 0.85 (0.721 to 0.954)
      with 10, 20 and 40 mA tetanic stimulations respectively. A sensitivity analysis
      using the Richmond Agitation Sedation Scale (RASS) confirmed the results. The 40
      mA stimulation was poorly tolerated. CONCLUSIONS: In deeply sedated mechanically
      ventilated patients, a pupil diameter variation >=5% during a 20 mA tetanic
      stimulation was highly predictable of insufficient analgesia during endotracheal
      suction. A 40 mA tetanic stimulation is painful and should not be used.

PMID- 23883684
TI  - The Sinorhizobium meliloti LysR family transcriptional factor LsrB is involved in
      regulation of glutathione biosynthesis.
AB  - Glutathione, a key antioxidant in Sinorhizobium meliloti, is required for the
      development of alfalfa (Medicago sativa) nitrogen-fixing nodules. This tripeptide
      can be synthesized by both gamma-glutamyl cysteine synthetase (GshA) and
      glutathione synthetase (GshB) in Escherichia coli and S. meliloti. Genetic
      evidence has indicated that the null mutant of S. meliloti gshA or gshB1 does not
      establish efficient symbiosis on alfalfa. However, the transcriptional regulation
      of gshA and gshB has not been well understood. Here, S. meliloti LsrB, a member
      of LysR family transcriptional factors, was found to positively regulate
      glutathione biosynthesis by activating the transcription of gshA and gshB1 under
      both free-living and symbiotic conditions. The decrease in glutathione production
      in the lsrB in-frame deletion mutant (lsrB1-2) was determined by using quadrupole
      time-of-flight liquid chromatography-mass spectrometry. The expression of gshA
      and gshB1 was correspondingly reduced in the mutant under free-living and
      symbiotic conditions by analyses of real-time quantitative reverse transcription
      polymerase chain reaction and promoter-GUS fusions. Interestingly, LsrB
      positively regulated the transcription of oxyR, which encodes another member of
      LysR family regulators and responds to oxidative stresses in S. meliloti. The
      oxyR null mutant produced less glutathione, in which the transcription of gshA
      was consistently down-regulated. These findings demonstrate that glutathione
      biosynthesis is positively regulated by both LsrB and OxyR in S. meliloti. 

PMID- 23883685
TI  - Enhanced parosmia and phantosmia in patients with severe depression.

PMID- 23883686
TI  - Factors associated with vitamin D deficiency in European adolescents: the HELENA
      study.
AB  - Evidence indicates low 25-hydroxyvitamin D [(25(OH)D] concentrations in European
      adolescents. Identification of potential determinants is therefore essential to
      guide public health initiatives aiming at optimizing vitamin D status across
      Europe. The aim of the study was to identify potential influencing factors of
      25(OH)D concentrations in European adolescents aged 12.5 to 17.5 y, participating
      in the multi-centre cross-sectional Healthy Lifestyle in Europe by Nutrition in
      Adolescence (HELENA) study. A subset of 1,006 participants (46.8% males) was
      drawn from the main study. Measures of body composition, biochemical markers,
      socioeconomic status, dietary intake, physical activity, fitness, sleep time and
      vitamin D genetic polymorphism (rs1544410) were assessed. Stepwise multivariate
      linear regression analysis was conducted stratified by gender. In males, linear
      regression of 25(OH)D, suggested that (1) winter season (beta=-0.364; p<0.01),
      (2) higher latitudes (beta=-0.246; p<0.01), (3) BMI z-score (beta=-0.198; p<0.05)
      and (4) retinol concentration (beta=0.171; p<0.05) independently influenced
      25(OH)D concentrations. In females, (1) winter season (beta=-0.370; p<0.01), (2)
      sleep time (beta=-0.231; p<0.01), (3) supplement intake (beta=0.221; p<0.05), (4)
      flexibility (beta=0.184; p<0.05), (5) body fat % (beta=0.201; p<0.05) (6), BMI z
      score (beta=-0.272; p<0.05), (7) higher latitudes (beta=-0.219; p<0.01) and (8)
      handgrip strength (beta=0.206; p<0.05) independently influenced 25(OH)D
      concentrations. Season, latitude, fitness, adiposity, sleep time and
      micronutrient supplementation were highly related to 25(OH)D concentrations found
      in European adolescents. 

PMID- 23883687
TI  - Insights on vitamin D's role in cardiovascular disease: investigating the
      association of 25-hydroxyvitamin D with the dimethylated arginines.
AB  - Accumulating evidence has stipulated a strong correlation between vitamin D
      (vitD) deficiency and cardiovascular disease (CVD); however, a mechanistic link
      is missing. This study investigated the association of vitD with endothelial
      dysfunction parameters. Subjects comprised male patients with verified coronary
      artery disease (CAD) (n=69) and age- and sex-matched controls (n=20). 25
      Hydroxyvitamin D [25(OH)D] was determined using high performance liquid
      chromatography with ultraviolet detection whereas asymmetric and symmetric
      dimethylarginine (ADMA and SDMA, respectively) were determined by liquid
      chromatography-mass spectrometry. Nitric oxide (NO) was determined
      spectrophotometrically and high-sensitivity C-reactive protein (hs-CRP) was
      determined using enzyme-linked immunosorbent assay (ELISA). Comparison of mean
      25(OH)D concentrations of patients and controls yielded a significant result
      (p=0.0002). 25(OH)D2 was dominant in patients whereas 25(OH)D3 was dominant in
      controls (p=0.003 and 0.001, respectively). Comparison of mean ADMA and SDMA
      concentrations of patients exhibiting normal and suboptimal vitD yielded
      insignificant results (p=0.692 and 0.998, respectively). Significant results were
      obtained from the comparison of mean hs-CRP and NO concentrations of patients
      exhibiting normal and suboptimal vitD (p=0.035 and 0.031, respectively). Results
      suggest involvement of vitD with the NO system, however not via modulation of the
      dimethylated arginines. A potential anti-inflammatory activity for vitD is also
      raised. 

PMID- 23883688
TI  - Urinary excretion levels of water-soluble vitamins in pregnant and lactating
      women in Japan.
AB  - Recent studies have shown that the urinary excretion levels of water-soluble
      vitamins can be used as biomarkers for the nutritional status of these vitamins.
      To determine changes in the urinary excretion levels of water-soluble vitamins
      during pregnant and lactating stages, we surveyed and compared levels of nine
      water-soluble vitamins in control (non-pregnant and non-lactating women),
      pregnant and lactating women. Control women (n=37), women in the 2nd (16-27 wk,
      n=24) and 3rd trimester of pregnancy (over 28 wk, n=32), and early- (0-5 mo,
      n=54) and late-stage lactating (6-11 mo, n=49) women took part in the survey. The
      mean age of subjects was ~30 y, and mean height was ~160 cm. A single 24-h urine
      sample was collected 1 d after the completion of a validated, self-administered
      comprehensive diet history questionnaire to measure water-soluble vitamins or
      metabolites. The average intake of each water-soluble vitamin was ? the estimated
      average requirement value and adequate intake for the Japanese Dietary Reference
      Intakes in all life stages, except for vitamin B6 and folate intakes during
      pregnancy. No change was observed in the urinary excretion levels of vitamin B2,
      vitamin B6, vitamin B12, biotin or vitamin C among stages. Urine nicotinamide and
      folate levels were higher in pregnant women than in control women. Urine
      excretion level of vitamin B1 decreased during lactation and that of pantothenic
      acid decreased during pregnancy and lactation. These results provide valuable
      information for setting the Dietary Reference Intakes of water-soluble vitamins
      for pregnant and lactating women. 

PMID- 23883689
TI  - Effect of dietary mineral sources and oil content on calcium utilization and
      kidney calcification in female Fischer rats fed low-protein diets.
AB  - We studied the effects of dietary mineral source and oil intake on kidney
      calcification in 4-wk-old female Fischer rats after consuming the AIN-76 purified
      diet (AIN-76). A modified AIN-76 mineral mixture was used, although the original
      calcium (Ca)/phosphorus (P) molar ratio remained unchanged. Rats were fed the
      modified diets for a period of 40 d before their kidneys were removed on the last
      day. Ca balance tests were performed on days 31 to 36 and biochemical analysis of
      urine was also studied. Kidney Ca, P, and magnesium (Mg) in the standard diet
      group (20% protein and 5% oil) were not affected by the mineral source. Kidney
      Ca, P, and Mg in the low-protein (10% protein) diet group, were found to be
      influenced by the dietary oil content and mineral source. In particular, the
      different mineral sources differentially increased kidney mineral accumulation.
      Pathological examination of the kidney showed that the degree of kidney
      calcification was proportional to the dietary oil content in the 10% dietary
      protein group, reflecting the calcium content of the kidney. The information
      gathered on mineral sources in this study will help future researchers studying
      the influence of dietary Ca/P molar ratios, and histological changes in the
      kidney. 

PMID- 23883690
TI  - Whey protein inhibits iron overload-induced oxidative stress in rats.
AB  - In this study, we evaluated the effects of whey protein on oxidative stress in
      rats that were subjected to oxidative stress induced by iron overload. Thirty
      male rats were assigned to 3 groups: the control group (regular [50 mg/kg diet]
      dose of iron+20% casein), iron overload group (high [2,000 mg/kg] dose of
      iron+20% casein, IO), and whey protein group (high dose of iron+10% casein+10%
      whey protein, IO+whey). After 6 wk, the IO group showed a reduction in the plasma
      total radical trapping antioxidant parameter and the activity of erythrocyte
      superoxide dismutase and an increase in lipid peroxidation (determined from the
      proportion of conjugated dienes). However, whey protein ameliorated the oxidative
      changes induced by iron overload. The concentration of erythrocyte glutathione
      was significantly higher in the IO+whey group than in the IO group. In addition,
      whey protein supplementation fully inhibited iron overload-induced DNA damage in
      leukocytes and colonocytes. A highly significant positive correlation was
      observed between plasma iron levels and DNA damage in leukocytes and colonocytes.
      These results show the antioxidative and antigenotoxic effects of whey protein in
      an in vivo model of iron overload-induced oxidative stress. 

PMID- 23883692
TI  - Lycopene/tomato consumption and the risk of prostate cancer: a systematic review
      and meta-analysis of prospective studies.
AB  - Lycopene/tomato has been discussed as a potential effecter in the prevention and
      therapy of prostate cancer; however, no systematic review has been reported to
      illustrate its effect recently. In the present study, a meta-analysis was carried
      out to determine whether intake of lycopene and tomato/tomato products could
      reduce the risk of prostate cancer. Eleven cohort studies and six nested case
      control studies were identified through searching of international journal
      databases and reference lists of relevant publications. Two reviewers
      independently assessed the study quality and extracted data from each identified
      study; only studies with sufficient quality were included in the review. The main
      outcome of interest was incidence of prostate cancer. Compared with consumers of
      lower raw tomato intake, the odds ratio (OR) of incidence of prostate cancer
      among consumers of higher raw tomato intake was 0.81 [95% confidential interval
      (CI) 0.59-1.10]; for consumers of higher level of cooked tomato intake versus
      lower cooked tomato intake, this OR was 0.85 (95% CI 0.69-1.06); the OR of higher
      lycopene intake versus lower lycopene intake for prostate cancer was 0.93 (95% CI
      0.86-1.01) and the OR for higher level of serum lycopene versus lower serum
      lycopene level was 0.97 (95% CI 0.88-1.08). It's suggested that tomato may play a
      modest role in the prevention of prostate cancer. Further research would be
      needed to determine the type and quantity of tomato products regarding their
      potential in preventing prostate cancer. 

PMID- 23883691
TI  - The effects of sports drink osmolality on fluid intake and immunoendocrine
      responses to cycling in hot conditions.
AB  - We investigated the effects of two carbohydrate-based sports drinks on fluid
      intake and immunoendocrine responses to cycling. Six well-trained male cyclists
      completed trials on three separate days that involved cycling at 60% VO(2peak)
      for 90 min in hot conditions (28.1 +/- 1.5oC and 52.6 +/- 3.1% relative
      humidity). During each trial, the subjects consumed ad libitum (1) an isotonic
      sports drink (osmolality 317 mOsm/kg), (2) a hypotonic sports drink (osmolality
      193 mOsm/kg) or (3) plain water. The cyclists consumed significantly (p<0.05)
      more of the isotonic drink (1.23 +/- 0.35 L) and hypotonic drink (1.44 +/- 0.55
      L) compared with water (0.73 +/- 0.26 L). Compared with water (-0.96 +/- 0.26
      kg), body mass decreased significantly less after consuming the hypotonic drink (
      0.50 +/- 0.38 kg) but not the isotonic drink (-0.51 +/- 0.41 kg). Blood glucose
      concentration was significantly higher at the end of the isotonic and hypotonic
      drink trials compared with the water trial. Neutrophil count and the plasma
      concentrations of catecholamines, interleukin 6 (IL-6), myeloperoxidase,
      calprotectin and myoglobin increased significantly during all three trials. IL-6
      and calprotectin were significantly lower following the hypotonic drink trial
      compared with the water trial. In conclusion, hypotonic sports drinks are
      appealing for athletes to drink during exercise, and may help to offset fluid
      losses and attenuate some inflammatory responses to exercise.

PMID- 23883693
TI  - Relative contribution of organs other than brain to resting energy expenditure is
      consistent among male power athletes.
AB  - We have previously shown that resting energy expenditure (REE) adjusted by fat
      free mass (FFM) in male college athletes remains consistent regardless of FFM.
      The FFM comprises internal organs with high metabolic activity, such as liver and
      brain, which account for 60 to 80% of REE in adults. The purpose of the present
      study is to examine the contribution of internal organs to the REE of the FFM
      fraction among male power athletes. The study included 37 American male college
      football players. REE was measured by indirect calorimetry and body composition
      was measured by dual energy X-ray absorptiometry (DXA). Mass of brain, liver, and
      kidneys was measured by MRI and mass of heart was estimated by echocardiography.
      Normal levels of thyroid hormone (triiodothyronine: T3) were confirmed in all
      subjects prior to the analysis. Multiple regression analysis was used to assess
      the influence of FFM, fat mass (FM), T3, and mass of organs on variance of REE.
      Average body weight and FFM were 81.2+/-11.3 kg and 67.7+/-7.4 kg, respectively.
      The relative contributions of liver, kidneys, and heart to REE were consistent
      regardless of FFM, while the REE of brain was negatively correlated with FFM (r=
      0.672, p<0.001). Only FFM and T3 were found to be independent factors influencing
      REE. These results suggest that a steady contribution of internal organs other
      than the brain is the major reason for the consistency of the REE/FFM ratio in
      male power athletes. 

PMID- 23883694
TI  - The effect of ethyl pyruvate supplementation on rat fatty liver induced by a high
      fat diet.
AB  - Continuous positive energy imbalance leads to obesity, which increases the risk
      of developing non-alcoholic fatty liver disease. The hepatoprotective effect of
      ethyl pyruvate has been revealed in several studies. Therefore, we examined the
      effect of ethyl pyruvate supplementation on liver cell damage, metabolism,
      membrane fluidity, and oxidative stress markers in rats fed a high-fat diet.
      After 6-wk feeding of a control or high-fat diet, Wistar rats were divided into 4
      groups: control diet, control diet and ethyl pyruvate, high-fat diet, and high
      fat diet and ethyl pyruvate. Ethyl pyruvate was administered as a 0.3% solution
      in drinking water, for the following 6 wk. Ethyl pyruvate intake attenuated the
      increase in activities of plasma transaminases and liver TNF-alpha. However, the
      supplementation was without effect in the lipid profiles, membrane fluidity or
      oxidative metabolism in liver induced by the high-fat diet. Our data confirm the
      potency of ethyl pyruvate against cell liver damage. Nevertheless, prolonged
      intake did not affect the development of a fatty liver. 

PMID- 23883695
TI  - Influences of maternal B12 and methionine intake during gestation and lactation
      on testicular development of offspring in rats.
AB  - The influence of maternal vitamin B12 malnutrition on testicular development of
      offspring was examined using soy protein-based B12-deficient diets with or
      without 0.5% DL-methionine supplementation. Dams were fed the B12-deficient diet
      throughout gestation and lactation, whereas dams in a control group were fed a
      control diet which contained cyanocobalamin in the B12-deficient diet without
      methionine. Offspring born to dams fed the B12-deficient diet without methionine
      showed poor testicular development, e.g. decreased numbers of seminiferous
      tubules containing healthy spermatocytes and a high ratio of apoptotic cells per
      all germ cells. The abnormality was rarely observed in the group fed the B12
      deficient diet with methionine. It was likely that the testicular abnormality of
      offspring was caused by B12-deficiency post partum and was prevented by the
      methionine supplementation. These observations suggested that maternal B12
      nutritional status during the pre-weaning period is quite important for
      spermatogenesis of male offspring and that the requirement of B12 for testicular
      development is to produce active B12-dependent methionine synthase.

PMID- 23883696
TI  - Cross-sectional study of possible association between rapid eating and high body
      fat rates among female Japanese college students.
AB  - The incidence of excessive body fat among young Japanese females with a normal
      BMI, which is referred to as normal weight obesity (NWO), has recently increased.
      Some studies have associated eating rates with BMI. However, an association
      between body fat rate and dietary habits has not been proven. We compared
      differences in dietary habits between 72 female Japanese junior college students
      with normal (<30%; normal body fat ratio, NFR) and high (>= 30%; excessive body
      fat ratio, EFR) proportions of body fat. Energy and the intake of many nutrients
      and foods did not significantly differ between the two groups, but the EFR group
      consumed significantly less saturated fatty acid, sugar and confectionery. Eating
      rapidly was significantly associated with body fat ratios. Our findings suggest
      that eating rapidly increases body fat ratios.

PMID- 23883697
TI  - Silk peptide intake increases fat oxidation at rest in exercised mice.
AB  - Silk peptides (SP) have been reported to decrease body weight and accumulate fat.
      We investigated the effects of SP administration by using an open circuit
      calorimetry system on resting energy expenditure and substrate utilization in
      resting mice for the duration of 24 h. Seven-week-old male ICR-mice were orally
      administered SP (800 mg/kg) for 2 wk and were subjected to endurance training.
      The results indicated that not only was oxygen uptake higher in the SP group than
      in the CON group (*p<0.05), but also the respiratory exchange rate was lower than
      that in the CON group for the duration of 24 h (**p<0.01). Moreover, fat
      oxidation was increased in the SP group. Body weight of the SP group was
      significantly decreased compared to that of the CON group (*p<0.05). These
      results suggest that intake of silk peptides increases fat oxidation during rest
      in exercised mice. Intake of silk peptides is considered to be a favorable
      supplement for athletes in training. In particular, it would be an effective
      supplement for athletes who require weight loss along with an increase in muscle
      mass. 

PMID- 23883698
TI  - Acute kidney injury is a frequent complication in critically ill neonates
      receiving extracorporeal membrane oxygenation: a 14-year cohort study.
AB  - INTRODUCTION: Newborns in need of extracorporeal membrane oxygenation (ECMO)
      support are at high risk of developing acute kidney injury (AKI). AKI may occur
      as part of multiple organ failure and can be aggravated by exposure to components
      of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally
      eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define
      systematically the incidence and clinical course of AKI in critically ill
      neonates receiving ECMO support. METHODS: This study reviewed prospectively
      collected clinical data (including age, diagnosis, ECMO course, and serum
      creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a
      14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal
      function, and End-stage renal disease (RIFLE) classification. SCr data were
      reviewed per ECMO day and compared with age-specific SCr reference values.
      Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure
      as 150%, 200%, or 300% of median SCr reference values). Data are presented as
      median and interquartile range (IQR) or number and percentage. RESULTS: Of 242
      patients included, 179 (74%) survived. Median age at the start of ECMO was 39
      hours (IQR, 26 to 63); median ECMO duration was 5.8 days (IQR, 3.9 to 9.4). In
      total, 153 (64%) patients had evidence of AKI, with 72 (30%) qualifying as Risk,
      55 (23%) as Injury, and 26 (11%) as Failure. At the end of the study period, only
      71 (46%) patients of all 153 AKI patients improved by at least one RIFLE
      category. With regression analysis, it was found that nitric oxide ventilation (P
      = 0.04) and younger age at the start of ECMO (P = 0.004) were significant
      predictors of AKI. Survival until intensive care unit discharge was significantly
      lower for patients in the Failure category (35%) as compared with the Non-AKI
      (78%), Risk (82%), and Injury category (76%), with all P < 0.001, whereas no
      significant differences were found between the three latter RIFLE categories.
      CONCLUSIONS: Two thirds of neonates receiving ECMO had AKI, with a significantly
      increased mortality risk for patients in the Failure category. As AKI during
      childhood may predispose to chronic kidney disease in adulthood, long-term
      monitoring of kidney function after ECMO is warranted.

PMID- 23883700
TI  - Comorbidity and premature mortality in epilepsy.

PMID- 23883699
TI  - Premature mortality in epilepsy and the role of psychiatric comorbidity: a total
      population study.
AB  - BACKGROUND: Epilepsy is associated with high rates of premature mortality, but
      the contribution of psychiatric comorbidity is uncertain. We assessed the
      prevalence and risks of premature mortality from external causes such as suicide,
      accidents, and assaults in people with epilepsy with and without psychiatric
      comorbidity. METHODS: We studied all individuals born in Sweden between 1954 and
      2009 with inpatient and outpatient diagnoses of epilepsy (n=69,995) for risks and
      causes of premature mortality. Patients were compared with age-matched and sex
      matched general population controls (n=660,869) and unaffected siblings
      (n=81,396). Sensitivity analyses were done to investigate whether these odds
      differed by sex, age, seizure types, comorbid psychiatric diagnosis, and
      different time periods after epilepsy diagnosis. RESULTS: 6155 (8.8%) people with
      epilepsy died during follow-up, at a median age of 34.5 (IQR 21.0-44.0) years
      with substantially elevated odds of premature mortality (adjusted odds ratio
      [aOR] of 11.1 [95% CI 10.6-11.6] compared with general population controls, and
      11.4 [10.4-12.5] compared with unaffected siblings). Of those deaths, 15.8%
      (n=972) were from external causes, with high odds for non-vehicle accidents (aOR
      5.5, 95 % CI 4.7-6.5) and suicide (3.7, 3.3-4.2). Of those who died from external
      causes, 75.2% had comorbid psychiatric disorders, with strong associations in
      individuals with co-occurring depression (13.0, 10.3-16.6) and substance misuse
      (22.4, 18.3-27.3), compared with patients with no epilepsy and no psychiatric
      comorbidity. INTERPRETATION: Reducing premature mortality from external causes of
      death should be a priority in epilepsy management. Psychiatric comorbidity plays
      an important part in the premature mortality seen in epilepsy. The ability of
      health services and public health measures to prevent such deaths requires
      review. FUNDING: Wellcome Trust, the Swedish Prison and Probation Service, and
      the Swedish Research Council.

PMID- 23883701
TI  - For the sake of beauty. Lyrical paintings by Giovanni Bosco.

PMID- 23883702
TI  - Magnons as pseudo-Goldstones in La-based cuprates: the effects of doping.
AB  - In the Neel phase of La-based cuprates, magnons are pseudo-Goldstones as the
      rotational symmetry of the spin system is explicitly broken by the small
      anisotropies. Respecting the approximate SO(3) symmetry we calculate the doping
      and temperature dependence of the magnon gaps in La2-xSrxCuO4 (LSCO) within the
      framework of the anisotropic linear sigma-model coupled to dipoles representing
      holes. We show that the temperature behaviour of the reduced magnon gaps depends
      weakly on the hole concentration and that the relative in-plane gap reduction
      with doping is insensitive to anisotropies of the parent compound. The obtained
      magnon gaps agree with experiments on LSCO, in particular the strong in-plane gap
      reduction with doping is reproduced. 

PMID- 23883704
TI  - Accreditation of microbiology laboratories: a perspective.

PMID- 23883703
TI  - Therapeutic antibodies and infectious diseases, Tours, France, November 20-22,
      2012.
AB  - The Therapeutic Antibodies and Infectious Diseases international congress was
      held in Tours, France on November 20-22, 2012. The first session was devoted to
      the development of antibodies directed against bacterial toxins or viruses that
      could be used in a potential bioterrorist threat situation. The second session
      dealt with the effector functions of anti-microbial antibodies, while the third
      was oriented toward anti-viral antibodies, with a special emphasis on antibodies
      directed against the human immunodeficiency and hepatitis C viruses. After a
      lecture by a speaker from the US Food and Drug Administration on antibody
      cocktails, the second day ended with a special session dedicated to discussions
      regarding the involvement of French biotechnology industries in the field. On the
      last day, the congress concluded with talks about current antibody treatments for
      infectious diseases, with a particular focus on their adverse events.
      Participants enjoyed this very stimulating and convivial meeting, which gathered
      scientists from various countries who had different scientific research
      interests. 

PMID- 23883705
TI  - Universal screening versus universal precautions in the context of preoperative
      screening for HIV, HBV, HCV in India.
AB  - In the Indian context, there is a convention of doing pre-operative screening for
      HIV, hepatitis B virus and hepatitis C viruses for all patients as a routine pre
      intervention investigation. This approach is justified in some instances in the
      best interest of the patient. However, as routine screening is not the standard
      care internationally and as there is a significant divergence of views about the
      merits and demerits of this practice, this issue needs to be debated in a
      rational manner with an evidence-based approach. The present article is authored
      by a surgeon and a microbiologist from a new cancer care centre in eastern India,
      who has attempted to address this contentious issue. The various available
      options have been explored, and advantages and disadvantages of the different
      approach have been discussed. An algorithm for infection prevention and control
      has been presented so that surgeons and medical microbiologists could manage
      infection control challenges satisfactorily. 

PMID- 23883706
TI  - Interleukin-5, interleukin-6, interleukin-8 and tumour necrosis factor-alpha
      levels obtained within 24-h of admission do not predict high-risk infection in
      children with febrile neutropenia.
AB  - PURPOSE: Biomarkers that can predict the severity of febrile neutropenia (FN) are
      potential tools for clinical practice. OBJECTIVE: The objective of this study is
      to evaluate the reliability of plasma interleukin (IL) levels as indicators of
      high-risk FN. MATERIALS AND METHODS: Children with haematological malignancies
      and FN were enrolled prospectively. A blood sample was obtained within 24-h of
      admission for estimation of IL-5, IL-6, IL-8 and tumour necrosis factor-alpha
      (TNF-alpha) level by the enzyme-linked immunosorbent assay. Patients were
      stratified into three groups. Group I (low-risk): No focus of infection; Group
      II: Clinical/radiological focus of infection; Group III: Microbiologically proven
      infection or FN related mortality. Groups II and III were analysed as high-risk.
      The cytokines were assessed at three different cut-off levels. RESULTS: A total
      of 52 episodes of FN in 48 patients were evaluated. The mean age was 6 years
      (range: 2-13). Primary diagnosis included acute lymphoblastic leukaemia (82%),
      non-Hodgkin's lymphoma (13%) and acute myeloid leukaemia (5%). Absolute
      neutrophil count was < 200 cells/MUl in half and 200-500 in 23%. Majority were
      categorised as Group I (69%), followed by Group II (16%) and III (15%). The range
      of IL-5 was too narrow and similar in the two risk-groups to be of any relevance.
      The best sensitivity of TNF-alpha and IL-6 for high-risk group was 78% and 70%,
      respectively. The highest specificity observed was 35%. The negative predictive
      value of IL-6, IL-8 and TNF-alpha exceeded 80%. CONCLUSION: IL-5, IL-6, IL-8 and
      TNF-alpha failed as predictors of clinically localised or microbiologically
      documented infection in children with chemotherapy induced FN. However, IL-6, IL
      8 and TNF-alpha could be useful in excluding the possibility of high-risk
      infection.

PMID- 23883707
TI  - Use of GenoType(r) MTBDRplus assay to assess drug resistance and mutation
      patterns of multidrug-resistant tuberculosis isolates in northern India.
AB  - PURPOSE: The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is
      a major public health problem. The diagnosis of MDR-TB is of paramount importance
      in establishing appropriate clinical management and infection control measures.
      The aim of this study was to evaluate drug resistance and mutational patterns in
      clinical isolates MDR-TB by GenoType(r) MTBDRplus assay. MATERIAL AND METHODS: A
      total of 350 non-repeated sputum specimens were collected from highly suspected
      drug-resistant pulmonary tuberculosis (PTB) cases; which were processed by
      microscopy, culture, differentiation and first line drug susceptibility testing
      (DST) using BacT/ALERT 3D system. RESULTS: Among a total of 125 mycobacterium
      tuberculosis complex (MTBC) strains, readable results were obtained from 120
      (96%) strains by GenoType(r) MTBDRplus assay. Only 45 MDR-TB isolates were
      analysed for the performance, frequency and mutational patterns by GenoType(r)
      MTBDRplus assay. The sensitivity of the GenoType(r) MDRTBplus assay for detecting
      individual resistance to rifampicin (RIF), isoniazid (INH) and multidrug
      resistance was found to be 95.8%, 96.3% and 97.7%, respectively. Mutation in
      codon S531L of the rpoB gene and codon S315T1 of katG genes were dominated in MDR
      TB strains, respectively (P < 0.05). CONCLUSIONS: The GenoType(r) MTBDRplus assay
      is highly sensitive with short turnaround times and a rapid test for the
      detection of the most common mutations conferring resistance in MDR-TB strains
      that can readily be included in a routine laboratory workflow.

PMID- 23883708
TI  - Multiple carbapenem hydrolyzing genes in clinical isolates of Acinetobacter
      baumannii.
AB  - PURPOSE: Carbapenem resistance in Acinetobacter baumannii has become highly
      rampant, which has been ascribed to the presence of multiple carbapenemases. The
      objective of the present study was to prospectively investigate the presence of
      multiple carbapenemase encoding genes in clinical isolates of A. baumannii.
      MATERIALS AND METHODS: A total of 30 imipenem resistant, consecutive non-repeat
      clinical isolates A. baumannii from a Tertiary Care Centre of Delhi were
      subjected to antimicrobial susceptibility testing (AST), screening for
      carbapenemase production by modified Hodge test (MHT) and determination of
      minimum inhibitory concentration for imipenem by E-Test(r) . These were subjected
      to Real time PCR for blaIMP-1 and 2 , blaVIM-1 and 2, blaOXA23, 24, 51 and 58
      using SYBR green-I. These were grouped together on the basis of their genotype as
      each isolate harboured multiple carbapenemases and correlated with their AST
      profile. Detection of the novel carbapenemase blaNDM-1 was performed by real time
      PCR using TaqMan probes on 14 isolates. RESULTS: Colistin appeared to be the most
      effective drug in vitro, followed by tetracycline and beta lactam/beta lactamase
      inhibitor combinations. All, but one isolate were positive for the MHT. All 30
      isolates were positive for blaOXA-51 like gene as well as blaIMP-1 and blaVIM-1
      genes. blaOXA 24 and 58 were not detected in any of the isolates. blaIMP-2 ,
      blaVIM-2 , blaOXA-23 were present in 15, 6 and 14 isolates respectively. Grouping
      based on the genotypic profile did not correlate with susceptibility pattern.
      Nine among the 14 isolates also harboured the novel blaNDM-1 gene. CONCLUSIONS:
      This is the first study from North India, which comprehensively detected the
      presence of multiple carbapenemases as well the blaNDM-1 gene. The presence of
      the novel gene blaNDM-1 indicated ability of A. baumannii to acquire new
      carbapenemase genes despite the existence of multiple carbapenemase genes. The
      present study confirmed the presence of multiple genetic mechanisms for
      carbapenemases production among the clinical isolates of A. baumannii in north
      India.

PMID- 23883709
TI  - Clonal diversity of New Delhi metallobetalactamase-1 producing Enterobacteriaceae
      in a tertiary care centre.
AB  - PURPOSE: New Delhi metallobetalactamase-1 (NDM-1) production is a major mechanism
      of resistance to carbapenems among the Enterobacteriaceae and is a cause for
      concern in the field of microbial drug resistance. This study was performed to
      detect NDM-1 in Enterobacteriaceae and to determine the clonal relatedness of NDM
      1 producing Escherichia coli and Klebsiella pneumoniae isolated from patients
      admitted in a tertiary care centre. MATERIALS AND METHODS: A total of 111
      clinically significant Enterobacteriaceae isolates, resistant to cephalosporin
      subclass III were screened for carbapenemase production by the modified Hodge
      test. Minimum inhibitory concentration to imipenem and meropenem was determined
      and interpreted according to Clinical Laboratory Standards Institute 2011
      criteria. Presence of bla NDM-1 was detected by polymerase chain reaction. To
      ascertain clonal relatedness, random amplification of polymorphic
      deoxyribonucleic acid (RAPD) was carried out for representative NDM-1 producers.
      RESULTS: bla NDM-1 was detected in 64 study isolates, of which 27 were
      susceptible to carbapenems. RAPD revealed a high degree of clonal diversity among
      NDM-1 producers except for a small clustering of isolates in the neonatal
      intensive care unit. CONCLUSION: There is extensive clonal diversity among the
      NDM-1 producing E. coli and K. pneumoniae. Hence, antibiotic selection pressure
      rather than horizontal transfer is probably an important operating factor for the
      emergence of NDM-1. This calls for increased vigilance, continuous surveillance
      and strict enforcement of antibiotic policy with restricted use of inducer drugs.

PMID- 23883710
TI  - Incidence of bla NDM-1 gene in Escherichia coli isolates at a tertiary care
      referral hospital in Northeast India.
AB  - PURPOSE: Increasing reports on New Delhi metallo-beta-lactamase-1 (NDM-1)
      producing Escherichia coli constitute a serious threat to global health since it
      is found to be highly resistant to most of the currently available antibiotics
      including carbapenems. This study has been performed to find out the incidence
      blaNDM-1 in E. coli isolates recovered from the various clinical samples at a
      tertiary care referral hospital in Northeast India. MATERIALS AND METHODS: A
      total of 270 non-duplicated E. coli isolates were recovered from the various
      clinical samples at a tertiary care referral hospital in Northeast India. All
      isolates with reduced susceptibility to meropenem or ertapenem (diameter of zones
      of inhibition, <= 21 mm) were further phenotypically confirmed for carbapenemase
      production by modified Hodge test. All screened isolates were also subjected to
      the polymerase chain reaction detection of blaNDM-1 gene and additional bla genes
      coding for transmission electron microscopy, SHV, CTX-M, and AmpC. RESULTS: Out
      of 270 E. coli isolates, 14 were screened for carbapenemase production on the
      basis of their reduced susceptibility to meropenem or ertapenem. All screened
      isolates were found to be positive for blaNDM-1 . Each of the blaNDM-1 possessing
      isolate was also positive for two or more additional bla genes, such as blaTEM ,
      blaCTX-M and blaAmpC . Phylogenetic analysis showed very less variation in blaNDM
      1 gene with respect to blaNDM-1 possessing E. coli isolates from other parts of
      India and abroad. CONCLUSIONS: Our findings highlight the incidence of blaNDM-1
      in E. coli isolates with a reduced susceptibility to meropenem or ertapenem.

PMID- 23883711
TI  - Co-existence of Pseudomonas-derived cephalosporinase among plasmid encoded CMY-2
      harbouring isolates of Pseudomonas aeruginosa in north India.
AB  - CONTEXT: In Pseudomonas aeruginosa, AmpC beta-lactamases are often responsible
      for high-level resistance to beta-lactam antibiotics. The co-production of
      plasmid-mediated AmpC along with chromosomal Pseudomonas-derived
      cephalosporinases thus remain a serious clinical concern owing to high resistance
      spectrum towards antibiotics. AIM: The present study was performed to investigate
      the co-existence of both chromosomally-encoded and plasmid-mediated AmpC beta
      lactamase among clinical isolates of P. aeruginosa. SETTING AND DESIGN: It is a
      cross-sectional study carried out in the Department of Microbiology in a tertiary
      referral hospital of northern India. METHODS AND METHODS: A total of 329
      consecutive, non-duplicate clinical isolates of P. aeruginosa, were selected for
      the detection of AmpC beta-lactamases and confirmed for AmpC production by
      modified three dimensional (M3D) test. Ceftazidime -imipenem antagonism test was
      used to detect inducible AmpC producers. Molecular characterisation of
      chromosomally-encoded blaPDC and plasmid-mediated AmpC gene was studied by
      performing polymerase chain reaction (PCR). RESULT: A total of 214 (65%) isolates
      were confirmed for AmpC production by M3D test. On performing multiplex PCR, 27
      isolates were detected posessing blaCMY type of plasmid-mediated AmpC gene. While
      48 isolates were found to harbour chromosomally-encoded blaPDC gene co-production
      of both chromosomal and plasmid-encoded AmpC was reported in eleven isolates.
      CONCLUSIONS: Although these chromosomally-encoded cephalosporinases might spread
      more slowly than mobilised AmpC, but it is likely that in the present scenario of
      intense antibiotic pressure, this will become an increasing problem and may
      further limit our antibiotic choices.

PMID- 23883712
TI  - Prevalence of hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis
      D virus and hepatitis E virus as causes of acute viral hepatitis in North India:
      a hospital based study.
AB  - CONTEXT: Acute viral hepatitis (AVH) is a major public health problem and is an
      important cause of morbidity and mortality. AIM: The aim of the present study is
      to determine the prevalence of hepatitis A virus (HAV), hepatitis B virus (HBV),
      hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV) as
      causes of AVH in a tertiary care hospital of North India. SETTINGS AND DESIGN:
      Blood samples and clinical information was collected from cases of AVH referred
      to the Grade I viral diagnostic laboratory over a 1-year period. SUBJECTS AND
      METHODS: Samples were tested for hepatitis B surface antigen, anti-HCV total
      antibodies, anti-HAV immunoglobulin M (IgM) and anti-HEV IgM by the enzyme-linked
      immunosorbent assay. PCR for nucleic acid detection of HBV and HCV was also
      carried out. Those positive for HBV infection were tested for anti-HDV
      antibodies. STATISTICAL ANALYSIS USED: Fisher's exact test was used and a P <
      0.05 was considered to be statistically significant. RESULTS: Of the 267 viral
      hepatitis cases, 62 (23.22%) patients presented as acute hepatic failure. HAV
      (26.96%) was identified as the most common cause of acute hepatitis followed by
      HEV (17.97%), HBV (16.10%) and HCV (11.98%). Co-infections with more than one
      virus were present in 34 cases; HAV-HEV co-infection being the most common. HEV
      was the most important cause of acute hepatic failure followed by co-infection
      with HAV and HEV. An indication towards epidemiological shift of HAV infection
      from children to adults with a rise in HAV prevalence was seen. CONCLUSIONS: To
      the best of our knowledge, this is the first report indicating epidemiological
      shift of HAV in Uttar Pradesh.

PMID- 23883713
TI  - Fungal rhinosinusitis: a prospective study in a University hospital of Uttar
      Pradesh.
AB  - BACKGROUND: To assess the purpose of fungal rhinosinusitis in a University
      hospital and to correlate histopathological findings with culture results for
      accurate clinical classification of the disease. MATERIALS AND METHODS: One
      hundred suspected patients were included in the study. Data was collected in a
      brief predetermined format. Samples like nasal lavages, sinus secretions, and
      tissue specimens were processed and examined by microbiology culture using
      recommended techniques. Slide culture was done to observe the microscopic
      morphology. Histopathological examination was done by H and E stain and PAS stain
      for classification. RESULTS: Out of 100 cases of rhinosinusitis, 21 cases were
      culture-positive for fungal rhinosinusitis. On the basis of histopathological
      findings, 14 cases (66.67%) were found to be of non-invasive fungal
      rhinosinusitis. Aspergillus flavus was the most common fungal isolate.
      CONCLUSION: Mycological profile of rhinosinusitis in Lucknow was thus evaluated.
      Histopathological and microbiological findings reported 21 cases of fungal
      rhinosinusitis among 100 suspected cases of rhinosinusitis.

PMID- 23883714
TI  - Study of the distribution of Malassezia species in patients with pityriasis
      versicolor and healthy individuals in Tertiary Care Hospital, Punjab.
AB  - PURPOSE: Pityriasis versicolor (PV) is a chronic superficial fungal disease
      caused by Malassezia species. Our aim was to identify Malassezia species from PV
      patients and healthy individuals in Punjab. MATERIALS AND METHODS: Modified Dixon
      agar was used as isolation culture medium. Identification was based on
      morphological observation and biochemical evaluation. The biochemical evaluation
      consisted of culture onto Sabouraud dextrose agar, catalase reaction, Tween
      assimilation, Cremophor EL assimilation, splitting of esculin and growth at 38 0
      C. RESULTS: Out of 58 microscopically diagnosed cases of PV, growth was obtained
      from 54 (93.10%) cases. The most frequently isolated species were M. globosa, M.
      sympodialis and M. furfur which made up 51.79%, 31.42% and 18.51% of the isolated
      etiological agents respectively. However, the major isolate from the back of
      healthy individuals was M. sympodialis (47.61%), followed by M. obtusa (19.04%),
      M. globosa (14.20%), M. furfur (9.52%), M. pachydermatis (4.76%) and M. slooffiae
      (4.76%). CONCLUSIONS: M. globosa in its mycelial phase was the main etiological
      agent, but as normal flora from the back of healthy subjects, it was found in
      significantly less number (P = 0.01), suggesting that the higher pathogenicity of
      M. globosa in terms of enzymatic endowment, might be the cause of its
      predominance in PV lesions.

PMID- 23883715
TI  - Assessment of reactivity of three treponemal tests in non-treponemal non-reactive
      cases from sexually transmitted diseases clinic, antenatal clinic, integrated
      counselling and testing centre, other different outdoor patient
      departments/indoor patients of a tertiary care centre and peripheral health
      clinic attendees.
AB  - In India, many state reference centres for sexually transmitted infections
      perform only a single screening assay for syphilis diagnosis. In this study,
      Treponema pallidum haemagglutination (TPHA) was performed on 1115 Venereal
      Disease Research Laboratory (VDRL)/rapid plasma regain (RPR) non-reactive and 107
      reactive sera out of 10,489 tested by VDRL/RPR according to the National AIDS
      Control Organisation syphilis testing protocol. A total of 47 Specimens reactive
      in TPHA and non-reactive with VDRL test were subjected to fluorescent treponemal
      antibody absorption and enzyme-immunoassay. Seroprevalence considering both VDRL
      and TPHA positivity was highest (4.4%) in sexually transmitted diseases clinic
      attendees than in other subject groups. Positivity by two treponemal tests in 24
      (2.2%) cases non-reactive by VDRL/RPR was representative of the fully treated
      patients or latent or late syphilis cases. The findings highlight that a suitable
      treponemal confirmatory test should be performed in all the diagnostic
      laboratories. 

PMID- 23883716
TI  - Mind the mind: results of a hand-hygiene research in a state-of-the-art cancer
      hospital.
AB  - Poor hand-hygiene (HH) is the primary cause of health-care related infections,
      yet compliance has proven to be challenging. This multi-method study into HH in a
      state-of-the-art cancer hospital demonstrates that the presence of resources and
      prioritisation of HH alone is not sufficient for HH compliance. A large gap was
      found between perceived (87%) and actual (52%) HH compliance and knowledge.
      Similarly, although 82% of the respondents knew proper HH moments, they did not
      act on it. These gaps between perception and reality suggest that resources,
      knowledge and training might not be sufficient for improving HH: Psychological
      barriers need to be addressed too. 

PMID- 23883717
TI  - Assessing effect of climate on the incidence of dengue in Tamil Nadu.
AB  - Incidence of dengue is reported to be influenced by climatic factors. The
      objective of this study is to assess the association of local climate with dengue
      incidence, in two geographically distinct districts in Tamil Nadu. The study uses
      climate data, rainfall and mean maximum and minimum temperature to assess its
      association if any, with dengue incidence in two districts of Tamil Nadu, South
      India. According to this study while precipitation levels have an effect on
      dengue incidence in Tamil Nadu, non-climatic factors such as presence of breeding
      sites, vector control and surveillance are important issues that need to be
      addressed. 

PMID- 23883718
TI  - Antimicrobial resistance pattern and in-vitro activity of azithromycin in
      Salmonella isolates [corrected].
AB  - We evaluated antimicrobial susceptibility pattern of 42 Salmonella isolates from
      February 2012 through January 2013. We also determined the minimum inhibitory
      concentrations (MICs) of azithromycin against Salmonella isolates and compared
      them with corresponding disc diffusion sizes. Entire 42 isolates were sensitive
      to chloramphenicol, 41 (97.6%) were sensitive to cotrimoxazole and amoxicillin
      each. MICs for azithromycin ranged from 2 MUg/ml to 24 MUg/ml, corresponding zone
      diameters ranged from 15 mm to 33 mm and the two were significantly correlated (P
      = 0.001). Our results indicate that whereas, azithromycin is a potential
      therapeutic option, the sensitivity to the first line drugs and absence of
      multidrug resistance reinforce the concept of antimicrobial recycling. 

PMID- 23883719
TI  - Characterisation of mumps virus genotype C among patients with mumps in India.
AB  - Measles, mumps and rubella (MMR) vaccine failure had been reported globally and
      here, we report that it occurs in India now. MMR vaccinated people have developed
      acute mumps accompanied by anti-mumps immunoglobulin M. Genotypic
      characterisation revealed that the circulating mumps strain was genotype C, which
      is distinct from the vaccine strain of genotype N (L-Zagreb). This is the first
      report in India to suggest that genotype C is responsible for the present mumps
      infection. Thus, the present MMR vaccine must be revamped and optimised for its
      efficacy to prevent any future mumps epidemics. 

PMID- 23883720
TI  - Elizabethkingia meningoseptica: an emerging pathogen causing meningitis in a
      hospitalized adult trauma patient.
AB  - A 23-year-old male patient who was a follow-up case of neurosurgery presented to
      our emergency department with a history of high-grade fever and clinical features
      of meningitis for 1 week. The cerebrospinal fluid (CSF) was sent to our
      laboratory for culture. The culture demonstrated growth of 1-2 mm in diameter
      light yellow coloured colonies of Gram-negative bacilli on chocolate and blood
      agar. There was no growth on MacConkey agar. The bacterium was multidrug
      resistant. Based upon the growth characteristics, bio-chemical reactions, drug
      susceptibility pattern and identification by Vitek 2 system the isolate was
      identified as Elizabethkingia meningoseptica. Patient was treated with injection
      piperacillin-tazobactam, injection vancomycin and cotrimoxazole tablets for 21
      days along with intrathecal injection of tigecycline and finally, patient
      improved clinically and the CSF cultures became sterile. The presence in hospital
      environment along with multidrug resistance makes E. meningoseptica a successful
      emerging nosocomial pathogen. 

PMID- 23883721
TI  - Microsporum gypseum dermatophytosis in a patient of acquired immunodeficiency
      syndrome: a rare case report.
AB  - Microsporum gypseum, a geophillic dermatophyte is rarely isolated from patients
      with acquired immunodeficiency syndrome. We report tinea corporis due to
      Microsporum gypseum, an uncommon aetiological agent, in a patient with acquired
      immunodeficiency syndrome from our region. The clinical presentation resembled
      psoriasis characterised by atypical, scaly and hyperkeratotic lesions. 

PMID- 23883722
TI  - Zero CD4 count: a case of discordant CD4 response in a patient with well
      suppressed viral load.
AB  - Human immunodeficiency virus (HIV) positive patients continue to have raise in
      CD4 cell for several years after initiation of anti-retroviral therapy (ART). The
      discordant response of static or fall in CD4 cells in presence of well-suppressed
      viral load is an unusual finding. In this communication, we present a case report
      of an HIV patient in whom the repeated CD4 enumerations consistently showed
      zero/nil CD4 counts before and after the start of ART in spite of maximum viral
      suppression. 

PMID- 23883723
TI  - Rhizomucor variabilis: a rare causative agent of primary cutaneous zygomycosis.
AB  - Rhizomucor variabilis is a rare cause of human infections. We report a case of
      primary cutaneous zygomycosis in an immunocompetent host. Although microscopy
      reveals the fungal aetiology, the need for species identification is highlighted
      to better understand the species and establish an epidemiological pattern as it
      is reported from restricted geographical locations. 

PMID- 23883724
TI  - Ochrobactrum anthropi: an unusual pathogen: are we missing them?
AB  - With increasing incidence of immunocompromised patients, many unusual organisms
      are emerging as pathogens in these patients. Ochrobactrum anthropi is an emerging
      opportunistic pathogen in immunocompromised patients. Here, we report two cases
      of neonates who presented with septicemia due to O. anthropi. Both were preterm
      and low birth weight babies admitted in the Neonatal Intensive Care Unit of our
      Hospital. One baby manifested with respiratory distress and eventually died. The
      second baby responded well to treatment and was discharged. The clinical
      presentation of infections along with microbiological characteristics and
      clinical significance of the organism are described. 

PMID- 23883725
TI  - Alternaria alternata in a case of mass in the lung.
AB  - A 50-year-old woman, an agriculture worker with diabetes and asthma presented to
      us with complaints of fever with chills, cough with scanty, mucopurulent sputum
      and dull aching chest pain in right mammary area radiating to axilla. Chest X-ray
      and computed tomography scan revealed mass in the right lung. Ultrasound guided
      fine-needle aspiration cytology was done and the greenish fluid on direct wet
      mount and inoculation on Sabouraud's dextrose agar isolated Alternaria species.
      Serum specimen was evaluated for immunoglobulin E specific titres for Alternaria
      species which was high. Patient was treated with fluconazole for 6 weeks after
      which the symptoms disappeared and chest X-ray was normal. 

PMID- 23883726
TI  - Streptococcus pasteurianus septicemia.
AB  - Streptococcus pasteurianus is part of the normal flora of the intestine. It has
      also been isolated from various infection sites. However, to date it has not been
      reported as a cause of fulminant septicemia and death. We report the post-mortem
      findings in a splenectomized hemophiliac patient with cirrhosis and concurrent
      human immunodeficiency virus (HIV), hepatitis B and hepatitis C infections. 

PMID- 23883727
TI  - Prevalence of hepatitis C virus infection among blood donors of Kumaon region of
      Uttarakhand.

PMID- 23883728
TI  - Seroprevalence of human immunodeficiency virus type 2 infection from a tertiary
      care hospital in Pune, Maharashtra: a 2 year study.

PMID- 23883729
TI  - Clinico-epidemiological profile of human immunodeficiency virus infection over a
      period of 3 years in a north Indian tertiary care hospital.

PMID- 23883730
TI  - Tuberculous cholecystitis.

PMID- 23883731
TI  - What should be the criteria for application of modified Hodge test for
      carbapenemases in Klebsiella pneumoniae?

PMID- 23883732
TI  - NDM-1 producers as causative agents of nosocomial urinary tract infections.

PMID- 23883733
TI  - Hand-held hazards by health-care workers.

PMID- 23883734
TI  - Diversity of Blastocystis subtypes in dogs in different geographical settings.
AB  - BACKGROUND: Blastocystis is a ubiquitous, globally distributed intestinal protist
      infecting humans and a wide range of animals. Several studies have shown that
      Blastocystis is a potentially zoonotic parasite. A 1996 study reported a 70%
      Blastocystis prevalence in Brisbane pound dogs while another study found that pet
      dogs/cats of 11 symptomatic Blastocystis infected patients harboured at least one
      Blastocystis subtype (ST) in common with the patient. These results raised the
      possibility that dogs might be natural hosts of Blastocystis. In this study, we
      aimed to investigate this hypothesis by estimating the prevalence of Blastocystis
      carriage and characterising the diversity of STs in dogs from three different
      environmental settings and comparing these STs with the range that humans
      harbour. METHODS: Two hundred and forty faecal samples from dogs from three
      different geographical regions with varying levels of socio-economic development
      and sanitation, namely i) 80 pet and pound dogs from Brisbane, Australia, ii) 80
      semi-domesticated dogs from Dong Village, Cambodia and iii) 80 stray dogs from
      the densely populated cities of Sikkim, Delhi and Mumbai in India, were screened
      for Blastocystis using PCR and subtyped based on the "barcode region" of the
      small subunit ribosomal RNA (SSU rRNA) gene. RESULTS: The prevalence of
      Blastocystis in dogs from Brisbane and Cambodia was 2.5% (2/80) and 1.3% (1/80),
      respectively, in contrast to 24% (19/80) in stray dogs from India. Stray dogs in
      India carried a diverse range of Blastocystis STs including ST 1, 4, 5 and 6
      while the dogs from Brisbane carried only ST1 and one Cambodian dog carried ST2.
      CONCLUSION: The results suggest there is geographical variation in Blastocystis
      prevalence and STs between dog populations as reported in human studies. In
      addition, the greater diversity of STs and higher prevalence of Blastocystis in
      Indian stray dogs compared to pet/pound and community dogs in Australia and
      Cambodia could reflect close proximity to humans and other animals and exposure
      to their faeces. It appears that dogs are not natural hosts for Blastocystis but
      rather are transiently and opportunistically infected with a diversity of STs.

PMID- 23883735
TI  - School performance and the risk of suicide attempts in young adults: a
      longitudinal population-based study.
AB  - BACKGROUND: Poor school performance is strongly associated with attempted
      suicide, but the mechanisms underlying this association are uncertain. We
      examined this relationship and the extent to which it is explained by (i) adult
      health behaviours and (ii) social conditions. Furthermore, we examined the
      potential modifying role of previous suicidal thoughts in the relationship.
      METHOD: We conducted a longitudinal cohort study of 6146 individuals aged 18-33
      years, recruited in 2002 and 2006 in Stockholm and resurveyed in 2007 and 2010
      respectively. We estimated the risk of reported lifetime suicide attempts at
      follow-up among individuals without a history of suicide attempts at baseline and
      in relation to compulsory school-leaving grades, controlling for possible
      confounders and mediators. RESULTS: There were 91 cases of self-reported suicide
      attempts during the follow-up (5-year incidence of 1.5%). ORs ranged from 3.35
      [95% confidence interval (CI) 1.88-5.96] for those in the lowest grade quartile
      to 2.60 (95% CI 1.48-4.57) and 1.76 (95% CI 0.99-3.13) for those in the second
      and third quartiles respectively. The relationship between school performance and
      risk of suicide attempts did not differ by sex. Adult health behaviours and
      social conditions marginally attenuated, but did not explain, the relationship.
      The gradient varied with baseline history of suicidal thoughts, and was found
      only among individuals without such a history. CONCLUSIONS: Poor school
      performance was found to predict suicide attempts among young adults without a
      history of suicidal thoughts. Adult health behaviours and social conditions did
      not explain this relationship. Instead, other factors linked with poor school
      performance, such as poor coping ability, may increase the risk of suicide
      attempts.

PMID- 23883737
TI  - Apurinic/apyrimidinic endonuclease 1, the sensitive marker for DNA deterioration
      in dextran sulfate sodium-induced acute colitis.
AB  - Mutations in mismatch repair (MMR) genes are commonly associated with the
      development of colorectal cancer. Additionally, base excision repair, which
      involves apurinic/apyrimidinic endonuclease 1 (APE1), recognizes and eliminates
      oxidative DNA damage. Here, we investigated the possible roles of APE1 in dextran
      sulfate sodium (DSS)-induced acute colitis using the young rat model. Four-week
      old Sprague-Dawley rats were administered 2% DSS in drinking water for 1 week.
      MMR and APE1 expression levels were assessed by western blotting and
      immunohistochemistry. Following DSS treatment, growth of young rats failed and
      the animals had loose stools. Together with the histological changes associated
      with acute colitis, APE1 and MSH2 levels increased significantly at 3 and 5 days
      after DSS treatment, respectively. The difference between APE1 and MSH2
      expression was significant. DSS-induced DNA damage and subsequent repair activity
      were evaluated by staining for 8-hydroxy-deoxyguanosine (8-OHdG) and APE1,
      respectively; 8-OHdG immunoreactivity increased throughout the colonic mucosa,
      while APE1 levels in the surface epithelium increased at an earlier timepoint.
      Taken together, our data suggest that changes in APE1 expression after DSS
      treatment occurred earlier and were more widespread than changes in MMR
      expression, suggesting that APE1 is more sensitive for prediction of DNA
      deterioration in DSS-induced colitis. 

PMID- 23883736
TI  - Noninvasive intracranial pressure estimation by orbital subarachnoid space
      measurement: the Beijing Intracranial and Intraocular Pressure (iCOP) study.
AB  - INTRODUCTION: The orbital subarachnoid space surrounding the optic nerve is
      continuous with the circulation system for cerebrospinal fluid (CSF) and can be
      visualized by using magnetic resonance imaging (MRI). We hypothesized that the
      orbital subarachnoid space width (OSASW) is correlated with and can serve as a
      surrogate for intracranial pressure (ICP). Our aim was to develop a method for a
      noninvasive measurement of the intracranial CSF-pressure (CSF-P) based on MRI
      assisted OSASW. METHODS: The prospective observational comparative study included
      neurology patients who underwent lumbar CSF-P measurement and 3.0-Tesla orbital
      magnetic resonance imaging (MRI) for other clinical reasons. The width of the
      orbital subarachnoid space (OSASW) around the optic nerve was measured with MRI
      at 3, 9, and 15 mm behind the globe. The study population was randomly divided
      into a training group and a test group. After adjusting for body mass index (BMI)
      and mean arterial blood pressure (MABP), algorithms for the associations between
      CSF-P and OSASW were calculated in the training group. The algorithms were
      subsequently verified in the test group. Main outcome measures were the width of
      the orbital subarachnoid space (OSASW) and the lumbar cerebrospinal fluid
      pressure (CSF-P). RESULTS: Seventy-two patients were included in the study. In
      the training group, the algorithms for the associations between CSF-P and OSASW
      were as follows: (a) CSF-P = 9.31 * OSASW (at 3 mm) + 0.48 * BMI + 0.14 * MABP
      19.94; (b) CSF-P = 16.95 * OSASW (at 9 mm) + 0.39 * BMI + 0.14 * MABP-20.90; and
      (c) CSF-P = 17.54 * OSASW (at 15 mm) + 0.47 * BMI + 0.13 * MABP-21.52. Applying
      these algorithms in the independent test group, the measured lumbar CSF-P (13.6
      +/- 5.1 mm Hg) did not differ significantly from the calculated MRI-derived CSF-P
      (OSASW at 3 mm: 12.7 +/- 4.2 mm Hg (P = 0.07); at 9 mm: 13.4 +/- 5.1 mm Hg (P =
      0.35); and at 15 mm: 14.0 +/- 4.9 mm Hg (P = 0.87)). Intraclass correlation
      coefficients (ICCs) were higher for the CSF-P assessment based on OSASW at 9 mm
      and at 15 mm behind the globe (all ICCs, 0.87) than for OSASW measurements at 3
      mm (ICC, 0.80). CONCLUSIONS: In patients with normal, moderately decreased or
      elevated ICP, MRI-assisted measurement of the OSASW appears to be useful for the
      noninvasive quantitative estimation of ICP, if BMI and MABP as contributing
      parameters are taken into account. TRIAL REGISTRATION: Clinical trial registered
      with the Chinese Clinical Trial Registry: ChiCTR-OCC-11001271.

PMID- 23883738
TI  - Patients with sepsis exhibit increased mitochondrial respiratory capacity in
      peripheral blood immune cells.
AB  - INTRODUCTION: In sepsis, mitochondria have been associated with both initial
      dysfunction and subsequent upregulation (biogenesis). However, the evolvement of
      mitochondrial function in sepsis over time is largely unknown, and we therefore
      investigated mitochondrial respiration in peripheral blood immune cells (PBICs)
      in sepsis patients during the first week after admission to the intensive care
      unit (ICU). METHODS: PBICs from 20 patients with severe sepsis or septic shock
      were analyzed with high-resolution respirometry 3 times after admission to the
      ICU (within 48 hours, days 3 to 4 and days 6 to 7). Mitochondrial DNA (mtDNA),
      cytochrome c (Cyt c), and citrate synthase (CS) were measured as indicators of
      cellular mitochondrial content. RESULTS: In intact PBICs with endogenous
      substrates, a gradual increase in cellular respiration reached 173% of controls
      after 1 week (P = 0.001). In permeabilized cells, respiration using substrates of
      complex I, II, and IV were significantly increased days 1 to 2, reaching 137%,
      130%, and 173% of controls, respectively. In parallel, higher levels of CS
      activity, mtDNA, and Cyt c content in PBICs (211%, 243%, and 331% of controls for
      the respective indicators were found at days 6 to 7; P < 0.0001). No differences
      in respiratory capacities were noted between survivors and nonsurvivors at any of
      the time points measured. CONCLUSIONS: PBICs from patients with sepsis displayed
      higher mitochondrial respiratory capacities compared with controls, due to an
      increased mitochondrial content, as indicated by increased mitochondrial DNA,
      protein content, and enzyme activity. The results argue against mitochondrial
      respiratory dysfunction in this type of cells in sepsis.

PMID- 23883739
TI  - Synthesis of Fe3O4/graphene/TiO2 composites for the highly selective enrichment
      of phosphopeptides from biological samples.
AB  - In this work, Fe3O4/graphene/TiO2 composites with a large surface area were
      designed and synthesized for the selective extraction and enrichment of
      phosphopeptides from biological samples. First, magnetic graphene was prepared
      according to our previous method. Next, we made the Fe3O4/graphene/TiO2 composite
      precursor using tetrabutyl titanate. Fe3O4/graphene/TiO2 composites were obtained
      after solvothermal and calcination treatments. We used standard protein-digestion
      solutions and human liver samples to test the enrichment ability of the obtained
      Fe3O4/graphene/TiO2 composites. The experimental results demonstrate that
      Fe3O4/graphene/TiO2 composites have a good phosphopeptide enrichment ability. 

PMID- 23883740
TI  - Conceptual domain of the matrix in fragmented landscapes.
AB  - In extensively modified landscapes, how the matrix is managed determines many
      conservation outcomes. Recent publications revise popular conceptions of a
      homogeneous and static matrix, yet we still lack an adequate conceptual model of
      the matrix. Here, we identify three core effects that influence patch-dependent
      species, through impacts associated with movement and dispersal, resource
      availability, and the abiotic environment. These core effects are modified by
      five 'dimensions': spatial and temporal variation in matrix quality; spatial
      scale; temporal scale of matrix variation; and adaptation. The conceptual domain
      of the matrix, defined as three core effects and their interaction with these
      five dimensions, provides a much-needed framework to underpin management of
      fragmented landscapes and highlights new research priorities. 

PMID- 23883741
TI  - Superconducting anisotropy in (CaCuO2)n/(SrTiO3)m superlattices.
AB  - The superconducting properties of (CaCuO2)n/(SrTiO3)m artificial superlattices
      have been investigated via transport measurements under the application of
      external magnetic fields. The coherence lengths in the plane of the substrate and
      in the direction perpendicular to it (xiab and xic, respectively) have been
      measured while varying m, the thickness of the SrTiO3 block. The results show
      that with increasing m, i.e. with increasing structural anisotropy, the
      superconducting anisotropy gamma = xiab/xic decreases. This apparent anomalous
      relation between the structural and the superconducting anisotropies suggests
      that gamma is more affected by local doping at the interface rather than by the
      separation between the superconducting blocks. This interpretation of the
      experimental results has been confirmed by both the irreversibility lines and the
      magnetic field dependence of the activation energy for fluxon motion. 

PMID- 23883742
TI  - Toward a second-person neuroscience.
AB  - In spite of the remarkable progress made in the burgeoning field of social
      neuroscience, the neural mechanisms that underlie social encounters are only
      beginning to be studied and could - paradoxically - be seen as representing the
      "dark matter" of social neuroscience. Recent conceptual and empirical
      developments consistently indicate the need for investigations that allow the
      study of real-time social encounters in a truly interactive manner. This
      suggestion is based on the premise that social cognition is fundamentally
      different when we are in interaction with others rather than merely observing
      them. In this article, we outline the theoretical conception of a second-person
      approach to other minds and review evidence from neuroimaging,
      psychophysiological studies, and related fields to argue for the development of a
      second-person neuroscience, which will help neuroscience to really "go social";
      this may also be relevant for our understanding of psychiatric disorders
      construed as disorders of social cognition. 

PMID- 23883743
TI  - Parameterising ecological validity and integrating individual differences within
      second-person neuroscience.
AB  - This commentary situates the second person account within a broader framework of
      ecological validity for experimental paradigms in social cognitive neuroscience.
      It then considers how individual differences at psychological and genetic levels
      can be integrated within the proposed framework. 

PMID- 23883744
TI  - Social cognition is not a special case, and the dark matter is more extensive
      than recognized.
AB  - The target article's approach is applauded, but it is suggested that the "dark
      matter" may be much larger than even the current authors suspect. Cartesian and
      mechanistic assumptions infuse not only the discipline of cognitive psychology,
      but all societal accounts of the person. A switch to dynamical accounts in which
      lawfulness is observed within a given systemic context is suggested. 

PMID- 23883745
TI  - The second person in "I"-"you"-"it" triadic interactions.
AB  - Second person social cognition cannot be restricted to dyadic interactions
      between two persons (the "I" and the "you"). Many instances of social
      communication are triadic, and involve a third person (the "him/her/it"), which
      is the object of the interaction. We discuss neuropsychological and brain imaging
      data showing that triadic interactions involve dedicated brain networks distinct
      from those of dyadic interactions. 

PMID- 23883746
TI  - Social affordances: is the mirror neuron system involved?
AB  - We question the idea that the mirror neuron system is the substrate of social
      affordances perception, and we suggest that most of the activity seen in the
      parietal and premotor cortex of the human brain is independent of mirroring
      activity as characterized in macaques, but rather reflects a process of one's own
      action specification in response to social signals. 

PMID- 23883747
TI  - Reciprocity between second-person neuroscience and cognitive robotics.
AB  - As there is "dark matter" in the neuroscience of individuals engaged in dynamic
      interactions, similar dark matter is present in the domain of interaction between
      humans and cognitive robots. Progress in second-person neuroscience will
      contribute to the development of robotic cognitive systems, and such developed
      robotic systems will be used to test the validity of the underlying theories. 

PMID- 23883748
TI  - On projecting grammatical persons into social neurocognition: a view from
      linguistics.
AB  - Though it draws on the grammatical metaphor of person (first, third, second) in
      terms of representations, Schilbach et al.'s target article does not consider an
      orthogonal line of evidence for the centrality of interaction to social
      cognition: the many grammatical phenomena, some widespread cross-linguistically
      and some only being discovered, which are geared to supporting real-time
      interaction. My commentary reviews these, and the contribution linguistic
      evidence can make to a fuller account of social cognition. 

PMID- 23883749
TI  - From synthetic modeling of social interaction to dynamic theories of brain-body
      environment-body-brain systems.
AB  - Synthetic approaches to social interaction support the development of a second
      person neuroscience. Agent-based models and psychological experiments can be
      related in a mutually informing manner. Models have the advantage of making the
      nonlinear brain-body-environment-body-brain system as a whole accessible to
      analysis by dynamical systems theory. We highlight some general principles of how
      social interaction can partially constitute an individual's behavior. 

PMID- 23883750
TI  - The brain as part of an enactive system.
AB  - The notion of an enactive system requires thinking about the brain in a way that
      is different from the standard computational-representational models. In
      evolutionary terms, the brain does what it does and is the way that it is, across
      some scale of variations, because it is part of a living body with hands that can
      reach and grasp in certain limited ways, eyes structured to focus, an autonomic
      system, an upright posture, etc. coping with specific kinds of environments, and
      with other people. Changes to any of the bodily, environmental, or
      intersubjective conditions elicit responses from the system as a whole. On this
      view, rather than representing or computing information, the brain is better
      conceived as participating in the action. 

PMID- 23883751
TI  - Why not the first-person plural in social cognition?
AB  - Through the mental alignment that sustains social interactions, the minds of
      individuals are shared. One interpretation of shared intentionality involves the
      ability of individuals to perceive features of the action scene from the
      perspective of the group (the "we-mode"). This first-person plural approach in
      social cognition is distinct from and preferable to the second-person approach
      proposed in the target article. 

PMID- 23883752
TI  - Talking to each other and talking together: joint language tasks and degrees of
      interactivity.
AB  - A second-person perspective in neuroscience is particularly appropriate for the
      study of communication. We describe how the investigation of joint language tasks
      can contribute to our understanding of the mechanisms underlying interaction. 

PMID- 23883753
TI  - Brain games: toward a neuroecology of social behavior.
AB  - In the target article, Schilbach et al. defend a "second-person neuroscience"
      perspective that focuses on the neural basis of social cognition during live,
      ongoing interactions between individuals. We argue that a second-person
      neuroscience would benefit from formal approaches borrowed from economics and
      behavioral ecology and that it should be extended to social interactions in
      nonhuman animals. 

PMID- 23883754
TI  - Second person neuroscience needs theories as well as methods.
AB  - Advancing second-person neuroscience will need strong theories, as well as the
      new methods detailed by Schilbach et al. I assess computational theories,
      enactive theories, and cognitive/information processing theories, and argue that
      information processing approaches have an important role to play in second-person
      neuroscience. They provide the closest link to brain imaging and can give
      important insights into social behaviour. 

PMID- 23883755
TI  - From the bottom up: the roots of social neuroscience at risk of running dry?
AB  - A second-person neuroscience, as an emerging area of neuroscience and the
      behavioral sciences, cannot afford to avoid a bottom-up, subcortical, and
      conative-affective perspective. An example with canid social play and a modern
      motivational behavioral neursocience will illustrate our point. 

PMID- 23883756
TI  - Advancing the neuroscience of social emotions with social immersion.
AB  - Second-person neuroscience offers a framework for the study of social emotions,
      such as embarrassment and pride. However, we propose that an enduring mental
      representation of oneself in relation to others without a continuous direct
      social interaction is possible. We call this state "social immersion" and will
      explain its impact on the neuroscience of social emotions. 

PMID- 23883757
TI  - A mature second-person neuroscience needs a first-person (plural) developmental
      foundation.
AB  - Schilbach et al.'s model assumes that the ability to "experience" minds is
      already present in human infants and therefore falls foul of the very
      intellectualist problems it attempts to avoid. We propose an alternative
      relational, action-based account, which attempts to grasp how the individual's
      construction of knowledge develops within interactions. 

PMID- 23883758
TI  - Merging second-person and first-person neuroscience.
AB  - Schilbach et al. contrast second-person and third-person approaches to social
      neuroscience. We discuss relations between second-person and first-person
      approaches, arguing that they cannot be studied in isolation. Contingency is
      central for converging first- and second-person approaches. Studies of embodiment
      show how contingencies scaffold first-person perspective and how the transition
      from a third- to a second-person perspective fundamentally involves first-person
      contributions. 

PMID- 23883759
TI  - A second-person approach cannot explain intentionality in social understanding.
AB  - A second-person approach that prioritizes dyadic emotional interaction is not
      well equipped to explain the origins of the understanding of mind conceived as
      intentionality. Instead, the critical elements that will deliver the
      understanding of self and other as persons with intentionality are shared object
      centered interactions that include not only emotional engagement, but also joint
      attention and joint goal-directed action. 

PMID- 23883760
TI  - Second-person neuroscience: implications for Wittgensteinian and Vygotskyan
      approaches to psychology.
AB  - Interactive approaches to development and social psychology may particularly
      benefit from the non-dualist features of a second-person neuroscience. In that
      context, I discuss the compatibility of a second-person neuroscience with a
      Wittgensteinian analysis of psychological concepts and its connections to a
      Vygotskyan approach to psychological development. 

PMID- 23883761
TI  - The use of non-interactive scenarios in social neuroscience.
AB  - Although we fundamentally agree with Schilbach et al., we argue here that there
      is still some residual utility for non-interactive scenarios in social
      neuroscience. They may be useful to quantify individual differences in prosocial
      inclination that are not influenced by concerns about reputation or social
      pressure. 

PMID- 23883762
TI  - What we can learn from second animal neuroscience.
AB  - There are several facets of second-person neuroscience which can benefit from
      comparisons with animal behavioral neuroscience studies. This commentary
      addresses the challenges involved in obtaining quantitative data from second
      person techniques, the role of stress in inducing robust responses, the use of
      interactive functional magnetic resonance imaging (fMRI), and the value of
      applying interactive methods to studies of aggression and depression. 

PMID- 23883763
TI  - Social perception and "spectator theories" of other minds.
AB  - We resist Schilbach et al.'s characterization of the "social perception" approach
      to social cognition as a "spectator theory" of other minds. We show how the
      social perception view acknowledges the crucial role interaction plays in
      enabling social understanding. We also highlight a dilemma Schilbach et al. face
      in attempting to distinguish their second-person approach from the social
      perception view. 

PMID- 23883764
TI  - Interaction versus observation: a finer look at this distinction and its
      importance to autism.
AB  - Although a second-person neuroscience has high ecological validity, the extent to
      which a second- versus third-person neuroscience approach fundamentally alters
      neural patterns of activation requires more careful investigation. Nonetheless,
      we are hopeful that this new avenue will prove fruitful in significantly
      advancing our understanding of typical and atypical social cognition. 

PMID- 23883765
TI  - Social affordances in context: what is it that we are bodily responsive to?
AB  - We propose to understand social affordances in the broader context of
      responsiveness to a field of relevant affordances in general. This perspective
      clarifies our everyday ability to unreflectively switch between social and other
      affordances. Moreover, based on our experience with Deep Brain Stimulation for
      treating obsessive-compulsive disorder (OCD) patients, we suggest that
      psychiatric disorders may affect skilled intentionality, including responsiveness
      to social affordances. 

PMID- 23883766
TI  - Further steps toward a second-person neuroscience.
AB  - Schilbach et al. contribute to neuroscience methodology through drawing on
      insights from the second-person approach. We suggest that they could further
      contribute to social neuroscience by more fully spelling out the ways in which a
      second-person approach to the nature and origin of thinking could transform
      neuroscience. 

PMID- 23883767
TI  - Mirror neurons are central for a second-person neuroscience: insights from
      developmental studies.
AB  - Based on mirror neurons' properties, viewers are emotionally engaged when
      observing others - even when not actively interacting; therefore, characterizing
      non-participatory action-viewing as isolated may be misleading. Instead, we
      propose a continuum of socio-emotional engagement. We also highlight recent
      developmental work that uses a second-person perspective, investigating
      behavioral, physiological, and neural activity during caregiver-infant
      interactions. 

PMID- 23883768
TI  - Toward a neuroscience of interactive parent-infant dyad empathy.
AB  - In accord with social neuroscience's progression to include interactive
      experimental paradigms, parents' brains have been activated by emotionally
      charged infant stimuli - especially of their own infant - including baby cry and
      picture. More recent research includes the use of brief video clips and
      opportunities for maternal response. Among brain systems important to parenting
      are those involved in empathy. This research may inform recent studies of
      decreased societal empathy, offer mechanisms and solutions. 

PMID- 23883769
TI  - It takes two to talk: a second-person neuroscience approach to language learning.
AB  - Language is a social act. We have previously argued that language remains
      embedded in sociality because the motivation to communicate exists only within a
      social context. Schilbach et al. underscore the importance of studying linguistic
      behavior from within the motivated, socially interactive frame in which it is
      learnt and used, as well as provide testable hypotheses for a participatory,
      second-person neuroscience approach to language learning. 

PMID- 23883770
TI  - Second-person social neuroscience: connections to past and future theories,
      methods, and findings.
AB  - We argue that Schilbach et al. have neglected an important part of the social
      neuroscience literature involving participants in social interactions. We also
      clarify some part of the models the authors discussed superficially. We finally
      propose that social neuroscience should take into consideration the effect of
      being observed and the complexity of the task as potentially influencing factors.

PMID- 23883772
TI  - Morphology of plantar interdigital neuroma: a comparative cadaveric study of
      elderly Finnish and Japanese individuals.
AB  - To examine morphological differences in Morton's interdigital neuroma between two
      elderly human populations, we conducted comparative study using 40 Japanese (27
      males, 13 females; mean age, 81.2 years) and 21 Finnish (6 males, 15 females;
      mean age, 80.5 years) cadavers. We defined the neuroma as a thickening of the
      nerve of at least two-fold relative to the non-pathological proximal part. The
      incidence of this neuroma was 25% (10/40) in the Japanese and 33.3% (7/21) in the
      Finnish cadavers. Moderate or severe hallux valgus (with an angle of more than 20
      degrees) was seen in half of the 40 Japanese cadavers (7 males, 13 females), but
      was absent in the Finnish cadavers. Such hallux valgus was present in 7 (5 males,
      2 females) of the 10 Japanese cadavers with neuroma. Moreover, in 2 Japanese
      cadavers, a paper-like, specialized type of neuroma was associated with the
      deformity. Pathogenesis of Morton's neuroma might be different between human
      populations with or without hallux valgus. 

PMID- 23883773
TI  - Collateral projections of the dorsal motor nucleus of the vagus nerve to the
      stomach and the intestines in the rat.
AB  - The vagal motor neurons project to the gastrointestinal tract by way of the
      gastric, celiac and hepatic branches of the vagus trunk. We have examined whether
      single neurons in the dorsal motor nucleus of the vagus nerve (DMV) have
      collateral projections to the stomach, the duodenum and the intestines using a
      double-labeling tracing method. Following application of Fluorogold to the cut
      end of the accessory celiac branch and injection of cholera toxin subunit b (CTb)
      into the body of stomach, many Fluorogold- and CTb-labeled neurons were found
      throughout the DMV. Most CTb-labeled neurons (about 90%) were also labeled with
      Fluorogold. When Fluorogold was applied to the cut end of the accessory celiac or
      the gastric branch and CTb was injected into the duodenum, many Fluorogold
      labeled neurons and CTb-labeled neurons were found in the DMV. About 20% of CTb
      labeled neurons were also labeled with Fluorogold. These results indicate that
      many neurons in the DMV send collateral projections to both the stomach and the
      intestines innervated by way of the celiac branch. However, many neurons in the
      DMV projecting to the duodenum do not project to the stomach or the intestines
      caudal to the duodenum. 

PMID- 23883774
TI  - Novel structure of hepatic extracellular matrices containing arylsulfatase A.
AB  - Arylsulfatase A (ArsA) has been regarded as a lysosomal enzyme involved in the
      degradation of sulfolipids. We previously reported the colocalization of non
      enzymatic ArsA with heparan sulfate proteoglycan on cell surfaces in the mouse
      liver using tissues processed with phosphate-buffered saline containing Ca2+ and
      Mg2+. In vitro analysis also revealed the tight binding of ArsA to heparin. These
      results suggest that ArsA functions as a component of the extracellular matrix
      (ECM). To characterize ArsA as a component of ECMs, we extended our comparison to
      the distribution patterns of ArsA and the major hepatic ECM components (types I,
      III, IV and V collagen, fibronectin, and laminin) in the mouse liver at the
      ultrastructural level under the same conditions that allow the detection of ArsA.
      Here, we show that ArsA is distributed not only on the cell surfaces of
      endothelial cells and hepatocytes, but also on the collagen fibrils in the space
      of Disse. ArsA is additionally colocalized with these major hepatic ECM
      components on both the luminal and abluminal sides of sinusoidal endothelial
      cells as well as in the space of Disse. These findings reveal a novel structure
      of hepatic ECMs containing ArsA. 

PMID- 23883775
TI  - Detection of regional myocardial ischaemia by a novel 80-electrode body surface
      Delta map in patients presenting to the emergency department with cardiac
      sounding chest pain.
AB  - BACKGROUND: Presentation with acute chest pain is common, but the conventional 12
      lead ECG has limitations in the detection of regional myocardial ischaemia. The
      previously described method of the body surface mapping system (BSM) Delta map,
      derived from an 80-electrode BSM, as well as a novel parameter total ischaemic
      burden (IB), may offer improved diagnostic sensitivity and specificity in
      patients with myocardial ischaemia. METHODS: The feasibility of using the novel
      BSM Delta map technique, and IB, for transient regional myocardial ischaemia was
      assessed in comparison with 12-lead ECG in 49 patients presenting to the
      emergency department (ED) with cardiac-sounding chest pain. RESULTS: The
      sensitivity and specificity of 12-lead ECG for the diagnosis of acute coronary
      syndrome (ACS) was 67 and 55%, respectively, positive likelihood ratio (+LR) 1.52
      [95% confidence interval (CI) 0.86, 2.70] and negative likelihood ratio (-LR)
      0.58 [95% CI 0.30, 1.12]. The sensitivity and specificity of the BSM Delta map
      for the diagnosis of ACS was 71 and 78%, +LR 3.19 [95% CI 1.31, 7.80], -LR 0.37
      [95% CI 0.20, 0.68]. There was a significantly positive correlation between peak
      troponin-I concentration and IB (r=0.437; P<0.002). CONCLUSION: This pilot study
      confirms the feasibility of using the Delta map for the diagnosis of ACS in
      patients presenting to the ED with cardiac-sounding chest pain and suggests that
      it has promising diagnostic accuracy and has superior sensitivity and specificity
      to the 12-lead ECG. The novel parameter of IB shows a significant correlation
      with troponin-I and is a promising tool for describing the extent of ischaemia.
      The use of the BSM Delta map in the ED setting could improve the diagnosis of
      clinically important ischaemic heart disease and furthermore presents the result
      in an intuitive manner, requiring little specialist experience. Further larger
      scale study is now warranted.

PMID- 23883776
TI  - The MISSED score, a new scoring system to predict Mortality In Severe Sepsis in
      the Emergency Department: a derivation and validation study.
AB  - OBJECTIVE: To derive and validate a new scoring system to predict in-hospital
      mortality in septic patients in the emergency department (ED). PATIENTS AND
      METHOD: Septic patients admitted to the ICU and those in whom early goal-directed
      therapy (EGDT) was carried out in the ED were identified from the ED record.
      Univariate and multivariate regression analyses identified independent variables
      associated with mortality. The variables were given a score weighted by the odds
      ratio, the sum of which yielded the Mortality In Severe Sepsis in the Emergency
      Department (MISSED) score. The performance of the MISSED score in predicting
      mortality was compared with that of the Acute Physiology and Chronic Health
      Evaluation II (APACHE II) score, the EGDT criteria and the severe sepsis
      criteria. The Hosmer-Lemeshow test was performed to calibrate the model. RESULTS:
      Independent variables identified were age at least 65 years, albumin level up to
      27 g/l and international normalized ratio of 1.2 or more. The MISSED score ranged
      from 0-9; cut-off point 5.5. Mortality rates associated with a score of 0, less
      than 5.5 and 5.5 or more were 7.4, 17.7 and 40.6%, respectively. The sensitivity
      of the score was 96.8% (95% confidence interval 87.8-99.4%). The mortality rate
      and specificity associated with a score of 9 were 62.9 and 91.6% respectively.
      The area under the curve for the MISSED score and the APACHE II score were equal.
      The performance of the MISSED score of 5.5 or more in predicting mortality was
      similar to that of the EGDT criteria. The sensitivity of the score was equal to
      that for the severe sepsis criteria. The Hosmer-Lemeshow test confirmed good
      calibration. CONCLUSION: The MISSED score should be used in the ED.

PMID- 23883782
TI  - Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for
      patients with locally advanced non-small-cell lung cancer? A pooled analysis of
      the literature.
AB  - INTRODUCTION: The purpose of this study was to evaluate whether consolidation
      chemotherapy (CCT) after concurrent chemo-radiotherapy is beneficial for patients
      with locally advanced non-small-cell lung cancer (LA-NSCLC). METHODS: We
      systematically searched PubMed for phase II/III trials published before December
      31, 2011, examining survival of LA-NSCLC treated with concurrent chemo
      radiotherapy. Median overall survival and other study characteristics were
      collected from each study and pooled. We extracted log-transformed hazards and
      standard errors under the assumption that survival follows an exponential
      distribution, and computed a pooled median overall survival and a 95% confidence
      interval (CI) using random-effects model. Collected trial arms were categorized
      as having CCT or not having it, CCT+ and CCT-, respectively. RESULTS: Forty-one
      studies were identified including seven phase III studies and 34 phase II studies
      with 45 arms (CCT+: 25; CCT-: 20). Clinical data were comparable for clinical
      stage, performance status, cancer histology, sex, and median age between the two
      groups. There was no statistical difference in pooled mOS between CCT+ (19.0
      month; 95% CI, 17.3-21.0) and CCT- (17.9 month; 95% CI, 16.1-19.9). Predicted
      hazard ratio of CCT+ to CCT- was 0.94 (95% CI, 0.81-1.09; p = 0.40). There were
      no differences between the two groups with regard to grade 3-5 toxicities in
      pneumonitis, esophagitis, and neutropenia. These models estimated that addition
      of CCT could not lead to significant survival prolongation or risk reduction in
      death for LA-NSCLC patients. CONCLUSION: The pooled analysis based on a
      publication basis failed to provide evidence that CCT yields significant survival
      benefit for LA-NSCLC.

PMID- 23883781
TI  - Impact of a physician recommendation and parental immunization attitudes on
      receipt or intention to receive adolescent vaccines.
AB  - Four vaccines are recommended by the Centers for Disease Control and Prevention's
      Advisory Committee on Immunization Practices for adolescents. Parental attitudes
      may play a key role in vaccination uptake in this age group. In 2011, we
      conducted a cross-sectional survey among parents of adolescents in one county in
      Georgia to identify parental attitudes toward adolescent vaccination, reasons for
      vaccine acceptance or refusal, and impact of a physician recommendation for
      vaccination. Physician recommendation was reported as one of the top reasons for
      receipt or intent to receive any of the vaccines. Physician recommendation of any
      of the four vaccines was associated with receipt of Tdap (p<0.001), MCV4
      (p<0.001), and HPV (p = 0.03) and intent to receive Tdap (p = 0.05), MCV4 (p =
      0.005), and HPV (p = 0.05). Compared with parents who did not intend to have
      their adolescent vaccinated with any of the vaccines, parents who did intend
      reported higher perceived susceptibility (3.12 vs. 2.63, p = 0.03) and severity
      of disease (3.89 vs. 3.70, p = 0.02) and higher perceived benefit of vaccination
      (8.48 vs. 7.74, p = 0.02). These findings suggest that future vaccination efforts
      geared toward parents may benefit from addressing the advantages of vaccination
      and enhancing social norms. Physicians can play a key role by providing
      information on the benefits of adolescent vaccination. 

PMID- 23883783
TI  - Resistance to EGFR-TKI can be mediated through multiple signaling pathways
      converging upon cap-dependent translation in EGFR-wild type NSCLC.
AB  - INTRODUCTION: For the majority of patients with non-small-cell lung cancer
      (NSCLC), response to epidermal growth factor receptor tyrosine kinase inhibitors
      (EGFR-TKIs) is suboptimal. In models of acquired resistance to EGFR-TKI,
      activation of Akt phosphorylation is frequently observed. Because Akt activation
      results in downstream initiation of cap-dependent protein translation, we
      hypothesized that a strategy of targeting cap-dependent translation in
      combination with erlotinib might enhance therapy. METHODS: NSCLC cells that are
      wild type for EGFR were assayed for sensitivity to erlotinib. Serum-starved NSCLC
      cells were assayed for EGFR signaling and downstream pathway activation by
      immunoblot after stimulation with epidermal growth factor. EGFR signaling and
      signaling mediators of cap-dependent translation were assayed by immunoblot under
      serum-replete conditions 24 hours after treatment with erlotinib. Finally,
      combination treatment with erlotinib and two different cap-dependent translation
      inhibitors were done to assess the effect on cell viability. RESULTS: EGFR
      signaling is coupled to activation of cap-dependent translation in EGFR wild-type
      cells. Erlotinib inhibits EGFR phosphorylation in EGFR-TKI resistant cells,
      however, results in activation of downstream signaling molecules including Akt
      and extracellular regulated kinase, ERK 1/2, resulting in maintenance of
      eukaryotic initiation factor 4F (eIF4F) activation. eIF4F cap-complex formation
      is maintained in erlotinib-resistant cells, but not in erlotinib-sensitive cells.
      Finally, using an antisense oligonucleotide against eukaryotic translation
      initiation factor 4E and a small-molecule inhibitor to disrupt eIF4F formation,
      we show that cap-dependent translation inhibition can enhance sensitivity to
      erlotinib. CONCLUSION: The results of these studies support further clinical
      development of translation inhibitors for treatment of NSCLC in combination with
      erlotinib.

PMID- 23883785
TI  - Protection of vascular endothelial cells injured by angiotensin II and hypoxia in
      vitro by Ginkgo biloba (Ginaton).
AB  - The objective of this study was to explore the protective effect and the possible
      mechanism of Ginkgo biloba extract (Ginaton) on human vascular endothelial cells
      (VECs) injured by angiotensin II (Ang-II) and hypoxia. The human aortic VECs were
      divided into different groups to observe the changes in endothelin (ET), calcium
      concentration ([Ca(2+)]i), and mitochondrial membrane potential (MMP). The
      results showed that Ginaton had inhibited ET secretion induced by hypoxia and Ang
      II (P < .01). the protection offered by Ginaton at mid (10 mg/mL) and low (5
      mg/mL) concentrations was obviously better than that offered at high
      concentration (25 mg/mL). The [Ca(2+)]i increased and MMP decreased significantly
      in both hypoxia group and Ang-II group (P < .01); however, the changes in
      [Ca(2+)]i and MMP could be meliorated by Ginaton. This study suggested that
      Ginaton could effectively protect VECs against injury, and the dose used
      clinically would rather be low than too high for getting better results.

PMID- 23883784
TI  - Clinical and biological role of secretory phospholipase A2 in acute respiratory
      distress syndrome infants.
AB  - INTRODUCTION: Secretory phospholipase A2 is supposed to play a role in acute lung
      injury but no data are available for pediatric acute respiratory distress
      syndrome (ARDS). It is not clear which enzyme subtypes are secreted and what the
      relationships are between enzyme activity, biophysical and biochemical
      parameters, and clinical outcomes. We aimed to measure the enzyme and identify
      its subtypes and to study its biochemical and biophysical effect. The secondary
      aim was to correlate enzyme activity with clinical outcome. METHODS:
      Bronchoalveolar lavage was performed in 24 infants with ARDS and 14 controls with
      no lung disease. Samples were assayed for secretory phospholipase A2 and
      molecules related to its activity and expression. Western blotting and captive
      bubble surfactometry were also performed. Clinical data were real time
      downloaded. RESULTS: Tumor necrosis factor-alpha (814 (506-2,499) vs. 287 (111
      1,315) pg/mL; P = 0.04), enzyme activity (430 (253-600) vs. 149 (61-387) IU/mL; P
      = 0.01), free fatty acids (4.3 (2.8-8.6) vs. 2 (0.8-4.6) mM; P = 0.026), and
      minimum surface tension (25.6 +/- 6.1 vs. 18 +/- 1.8 mN/m; P = 0.006) were higher
      in ARDS than in controls. Phospholipids are lower in ARDS than in controls (76.5
      (54-100) vs. 1,094 (536-2,907) MUg/mL; P = 0.0001). Three enzyme subtypes were
      identified (-IIA, -V, -X), although in lower quantities in controls; another
      subtype (-IB) was mainly detected in ARDS. Significant correlations exist between
      enzyme activity, free fatty acids (rho = 0.823; P < 0.001), and surface tension
      (rho = 0.55; P < 0.028). Correlations also exist with intensive care stay (rho =
      0.54; P = 0.001), PRISM-III24 (rho = 0.79; P< 0.001), duration of ventilation
      (rho = 0.53; P = 0.002), and oxygen therapy (rho = 0.54; P = 0.001). CONCLUSIONS:
      Secretory phospholipase A2 activity is raised in pediatric ARDS and constituted
      of four subtypes. Enzyme correlates with some inflammatory mediators, surface
      tension, and major clinical outcomes. Secretory phospholipase A2 may be a
      clinically relevant target in pediatric ARDS.

PMID- 23883786
TI  - Impact of meteorological conditions on abdominal aortic aneurysm rupture:
      evaluation of an 18-year period and review of the literature.
AB  - OBJECTIVE: To examine the influence of local meteorological conditions on the
      onset of ruptured abdominal aortic aneurysms (AAA). METHODS: A review of 6551
      consecutive days with a total of 191 ruptured AAA was performed between January,
      1994 and December, 2011. Days with and without ruptured AAA were compared
      considering local meteorological data. A systematic review of the literature was
      performed. RESULTS: Atmospheric pressure, cloudiness, relative humidity,
      precipitation, and water vapor pressure were comparable at event and nonevent
      days. The 4-day variance of atmospheric pressure prior to event days was
      significantly higher compared to nonevent days. Maximal and average temperature
      and water vapor pressure were significant lower at event days. Binary regression
      analysis identified a higher 4-day variance in atmospheric pressure as an
      independent factor for ruptures. CONCLUSIONS: Further studies-collected at
      different geographic and climate areas-are necessary to prove that meteorological
      conditions may trigger the incidence of ruptured AAA.

PMID- 23883787
TI  - Delayed presentation and management of blunt traumatic inferior gluteal artery
      pseudoaneurysm with associated arteriovenous fistula.
AB  - Disruption of arterial wall integrity as a result of trauma, iatrogeny,
      inflammation, or infection may result in pseudoaneurysm formation. Gluteal artery
      aneurysms are rare and represent less than 1% of all arterial aneurysms.
      Pseudoaneurysms of the inferior gluteal artery (IGA) following blunt trauma are
      exceptionally rare with only 6 reported cases in the English literature. We
      describe an 82-year-old female with a remote history of a fall presenting with an
      enlarging buttock mass. Imaging confirmed an IGA pseudoaneurysm with associated
      arteriovenous fistula that was successfully treated with endovascular
      embolization. 

PMID- 23883789
TI  - Human corneal endothelium regeneration: effect of ROCK inhibitor.

PMID- 23883790
TI  - RNFL damage after treatment for retinal detachment.

PMID- 23883791
TI  - The emerging novel Middle East respiratory syndrome coronavirus: the "knowns" and
      "unknowns".
AB  - A novel lineage C betacoronavirus, originally named human coronavirus EMC/2012
      (HCoV-EMC) and recently renamed Middle East respiratory syndrome coronavirus
      (MERS-CoV), that is phylogenetically closely related to Tylonycteris bat
      coronavirus HKU4 and Pipistrellus bat coronavirus HKU5, which we discovered in
      2007 from bats in Hong Kong, has recently emerged in the Middle East to cause a
      severe acute respiratory syndrome (SARS)-like infection in humans. The first
      laboratory-confirmed case, which involved a 60-year-old man from Bisha, the
      Kingdom of Saudi Arabia (KSA), who died of rapidly progressive community-acquired
      pneumonia and acute renal failure, was announced by the World Health Organization
      (WHO) on September 23, 2012. Since then, a total of 70 cases, including 39
      fatalities, have been reported in the Middle East and Europe. Recent clusters
      involving epidemiologically-linked household contacts and hospital contacts in
      the Middle East, Europe, and Africa strongly suggested possible human-to-human
      transmission. Clinical and laboratory research data generated in the past few
      months have provided new insights into the possible animal reservoirs,
      transmissibility, and virulence of MERS-CoV, and the optimal laboratory
      diagnostic options and potential antiviral targets for MERS-CoV-associated
      infection. 

PMID- 23883788
TI  - Why do only some hyperopes become strabismic?
AB  - Children with hyperopia greater than +3.5 diopters (D) are at increased risk for
      developing refractive esotropia. However, only approximately 20% of these
      hyperopes develop strabismus. This review provides a systematic theoretical
      analysis of the accommodation and vergence oculomotor systems with a view to
      understanding factors that could either protect a hyperopic individual or
      precipitate a strabismus. The goal is to consider factors that may predict
      refractive esotropia in an individual and therefore help identify the subset of
      hyperopes who are at the highest risk for this strabismus, warranting the most
      consideration in a preventive effort. 

PMID- 23883792
TI  - Factors related to the time to cryptorchidism surgery--a nationwide, population
      based study in Taiwan.
AB  - BACKGROUND/PURPOSE: Current guidelines recommend that the optimal timing for
      cryptorchidism surgery is by the age of 12 months. This study investigated the
      trend of surgical timing and examined the factors associated with time to surgery
      for cryptorchidism in Taiwan by using a nationwide, population-based database.
      METHODS: The present study utilized the Longitudinal Health Insurance Database
      2005, a subset of the National Health Insurance Research Database, which contains
      data on all paid medical benefit claims over the period 1997-2007 for a subset of
      1 million beneficiaries randomly drawn from 22.72 million individuals enrolled in
      the National Health Insurance program in 2005. We analyzed the timing of surgery
      in boys younger than 18 years with diagnosis of cryptorchidism. RESULTS: We
      identified 547 boys who underwent surgery under 18 years of age. Approximately
      79.2% of study participants received surgery after the age of 12 months. A
      multivariate analysis showed that several factors were significantly associated
      with time to surgery: age of the physician making the diagnosis, age of the
      surgeon performing the surgery, age of the patient at the first diagnosis of
      cryptorchidism, and number of previous clinic visits with the diagnosis of
      cryptorchidism and urbanization level of the patient's residence. CONCLUSION: A
      surprisingly high rate (79.2%) of all study participants underwent surgery beyond
      the optimal timing. Certain doctor and patient factors were associated with time
      to cryptorchidism surgery. Improving the alertness and education of parents and
      specialists may lead to earlier surgeries.

PMID- 23883793
TI  - Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late
      life: analysis of gene-environment interaction for the risk of dementia and
      Alzheimer's disease dementia.
AB  - BACKGROUND: As physical activity may modify the effect of the apolipoprotein E
      (APOE) epsilon4 allele on the risk of dementia and Alzheimer's disease (AD)
      dementia, we tested for such a gene-environment interaction in a sample of
      general practice patients aged ?75 years. METHOD: Data were derived from follow
      up waves I-IV of the longitudinal German study on Ageing, Cognition and Dementia
      in Primary Care Patients (AgeCoDe). The Kaplan-Meier survival method was used to
      estimate dementia- and AD-free survival times. Multivariable Cox regression was
      used to assess individual associations of APOE epsilon4 and physical activity
      with risk for dementia and AD, controlling for covariates. We tested for gene
      environment interaction by calculating three indices of additive interaction.
      RESULTS: Among the randomly selected sample of 6619 patients, 3327 (50.3%)
      individuals participated in the study at baseline and 2810 (42.5%) at follow-up
      I. Of the 2492 patients without dementia included at follow-up I, 278 developed
      dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The
      presence of the APOE epsilon4 allele significantly increased and higher physical
      activity significantly decreased risk for dementia and AD. The co-presence of
      APOE epsilon4 with low physical activity was associated with higher risk for
      dementia and AD and shorter dementia- and AD-free survival time than the presence
      of APOE epsilon4 or low physical activity alone. Indices of interaction indicated
      no significant interaction between low physical activity and the APOE epsilon4
      allele for general dementia risk, but a possible additive interaction for AD
      risk. CONCLUSIONS: Physical activity even in late life may be effective in
      reducing conversion to dementia and AD or in delaying the onset of clinical
      manifestations. APOE epsilon4 carriers may particularly benefit from increasing
      physical activity with regard to their risk for AD.

PMID- 23883797
TI  - Management of radiation-induced early nasal adhesion after radiotherapy for
      nasopharyngeal carcinoma.
AB  - BACKGROUND: This study investigates the conservative management of radiation
      induced early nasal adhesion after radiotherapy for nasopharyngeal carcinoma
      (NPC). METHODS: From June 2008 to June 2010, patients with bilateral or
      unilateral early nasal adhesion after radiotherapy for NPC were selected. All
      patients received endoscopic management and then nasal irrigation daily and nasal
      steroids spray for at least 3 months. All of the clinical data and follow-up
      endoscopy were analyzed. RESULTS: There were 40 patients enrolled. The mean
      follow-up period was 19.6 months (range, 12-24 months) after procedure. Thirty
      eight patients (95%) had patent nasal cavity during follow-up. Two patients (5%)
      had not received endoscopy regularly and developed severe fibrosis. For the whole
      group, nasal obstruction, rhinorrhea, hyposmia, and xerostomia all were improved
      from before management according to visual analog score (p < 0.05). CONCLUSION:
      Therapeutic endoscopy in combination with nasal steroid sprays and nasal
      irrigation provides a convenient, simple, effective, and minimally invasive
      therapy to treat early radiation-induced nasal adhesion patients.

PMID- 23883798
TI  - Relationship of eosinophils and plasma cells to biofilm in chronic
      rhinosinusitis.
AB  - BACKGROUND: This study investigates the relationship of eosinophils and plasma
      cells to biofilm in chronic rhinosinusitis (CRS). A prospective observational
      study was performed at the Keck Hospital, University of Southern California,
      Department of Otolaryngology, Los Angeles, CA. METHODS: A total of 29 patients,
      20 undergoing endoscopic sinus surgery for CRS and 9 control patients undergoing
      septoplasty for nasal obstruction without history or evidence of CRS, were
      included in this study. Contiguous sinonasal mucosa sample sections were examined
      by hematoxylin and eosin (H&E), fluorescence in situ hybridization (FISH), and
      immunohistochemistry (IHC) for biofilm, microbes, eosinophil major basic protein
      (EMBP), and cluster designation 27 (CD27). EMBP and CD27 were used as eosinophil
      and plasma cell markers, respectively. RESULTS: Biofilm was visualized in 15 of
      20 patients with CRS on H&E sections, confirmed by microbial presence using FISH.
      Biofilm was not identified in tissue samples of the nine control patients. On IHC
      analysis, CD27 and EMBP expression were significantly higher in patients with CRS
      compared with control (p < 0.05) and had greater expression in biofilm-positive
      patients compared with biofilm-negative patients. Nasal polyps correlated with
      higher expression of CD27 and EMBP, but in CRS patients without polyps CD27 and
      EMBP was also significantly greater in biofilm-positive specimens compared with
      biofilm-negative specimens. CONCLUSION: Biofilm presence in CRS appears to
      correlate to host inflammatory response involving plasma cell and eosinophil
      recruitment.

PMID- 23883799
TI  - Bacterial biofilm formation after nasal packing in nasal mucosa-wounded mice.
AB  - BACKGROUND: Bacterial biofilm plays an important role in recalcitrant chronic
      rhinosinusitis. Staphylococcus aureus is a crucial pathogen in chronic
      rhinosinusitis and S. aureus biofilm is related to unfavorable postoperative
      outcomes. Although S. aureus is known to be the most common bacteria leading to
      postoperative infection, whether biofilm forms on the wound surface after
      functional endoscopic sinus surgery and the relationship between biofilm
      formation and surgery are still not clear. This study was designed to observe
      whether S. aureus biofilm forms in mice with wounded nasal mucosa mice after
      bacteria inoculation. METHODS: Three hundred twenty-four wild-type male C57BL/6
      mice were recruited for the experiment. Except for the four used in the
      preliminary experiment, the mice were randomly divided into four groups: a wound
      plus packing group (group A), a wound group (group B), a packing group (group C),
      and a control group (group D). After treatment, groups A, B, and C were
      inoculated with S. aureus suspension at 1 * 10(9) CFU/mL in the right nasal
      cavity; sterile physiological saline was used instead of bacteria suspension for
      group D. Confocal laser scanning microscopy was used to detect the biofilm. A
      nasal lavage culture was also completed. RESULTS: Biofilm formation was found in
      group A on the 3rd, 7th, and 15th days after inoculation with growth rates of 10,
      25, and 40%, respectively. Three cases of biofilm were also detected in group B
      on the 15th day postinoculation. There was no biofilm observed on the nasal
      mucosa in group C or D. The nasal lavage culture showed that the inoculated
      bacteria stayed on the nasal mucosa temporarily after inoculation. CONCLUSION:
      Our results indicate that a nasal wound, nasal packing, and the existence of
      pathogenic bacteria are all essential elements for biofilm formation in healthy
      mice. This result indicated that biofilm formation may be avoided by shortening
      the duration of nasal packing and reducing the nasal wound.

PMID- 23883800
TI  - Objective olfactory outcomes after revision endoscopic sinus surgery.
AB  - BACKGROUND: Patients who suffer from hyposmia and anosmia report a negative
      effect on their overall quality of life. Smell disturbance of patients with
      chronic rhinosinusitis (CRS) can improve after endoscopic sinus surgery (ESS).
      Although several studies have shown that 50-83% of patients may notice an
      improvement in olfactory function after ESS, the olfactory improvement after
      revision ESS (RESS), especially by objective measurements, is still lacking.
      METHODS: Olfactory function was assessed by the traditional Chinese version of
      the University of Pennsylvania Smell Identification Test (UPSIT-TC)
      preoperatively and postoperatively, recorded as smell identification test (SIT)
      score. Olfactory outcomes from anosmia to hyposmia/normosmia, or from hyposmia to
      normosmia, were considered as "improvement." Postoperative assessments were
      divided into two periods: period 1 (P1) is defined as >6 but <12 months
      postoperatively; period 2 (P2) is defined as >12 but <24 months postoperatively.
      RESULTS: Thirty-two patients with smell disturbance preoperatively (period 0
      [P0]) and confirmed by UPSIT-TC were enrolled into this study. Mean SIT score at
      P0 was 13.3; mean SIT score at P1 was 18.6; mean SIT score at P2 was 20.4. The
      presence of nasal polyps blocking the olfactory cleft were associated with better
      olfaction improvements (p < 0.05) as was the degree of mucosal swelling. The
      overall improvement rates were 44.8 and 47.8% at P1 and P2, respectively.
      CONCLUSION: RESS resulted in objective evidence of olfactory improvement in
      approximately one-half of our cohort over 16 months of follow-up and offers a
      treatment option for an otherwise poor prognosis condition.

PMID- 23883801
TI  - Sinonasal complications resulting from dental treatment: outcome-oriented
      proposal of classification and surgical protocol.
AB  - BACKGROUND: Odontogenic sinusitis is a relevant infectious condition of the
      paranasal sinuses. The widespread use of dental implants and reconstructive
      procedures for dental implant placement has led to new types of complication. To
      the authors' knowledge, no publication has extensively examined sinonasal
      complications resulting from dental treatment, and no classification system
      allowing standardization and comparison of results is currently available. This
      study was designed to (a) analyze the results obtained from surgical treatment of
      complications resulting from dental procedures combining functional endoscopic
      sinus surgery (FESS) and an intraoral approach and (b) propose a new
      classification system and standardized treatment protocols for sinonasal
      complications resulting from dental procedures. METHODS: A total of 257 patients
      consecutively treated with FESS (136 in conjunction with oral surgery) were
      included in the study. Different clinical situations were integrated into a new
      classification system based on the pathogenesis and clinical aspects of each
      case, with the aim of identifying homogenous treatment groups. Results were
      evaluated for each class. RESULTS: Of the 257 patients, 254 were successfully
      treated with surgery performed according to the proposed protocols. Three of 257
      patients required a second surgery, after which they completely recovered.
      Complications of implant and preimplant surgery (maxillary sinus floor elevation)
      showed longer recovery times. CONCLUSION: The results obtained are very
      encouraging. The majority of patients (254/257; 98.8%) were successfully treated
      with the proposed protocols. These results seem to indicate that the
      rationalization of surgical treatment protocols according to the initial clinical
      situation may significantly improve the clinical outcome.

PMID- 23883802
TI  - Bacille Calmette-Guerin vaccination is associated with lower prevalence of
      allergic diseases in Indian children.
AB  - BACKGROUND: Immunization with bacille Calmette-Guerin (BCG) has been shown to
      augment T helper (Th) 1 biased response and hence gives protection against
      developing allergies. However, results across the studies have been inconclusive
      and there is no Indian study verifying this association. We explored the link
      between BCG vaccination and prevalence of allergic diseases among school children
      of Chandigarh, North India. METHODS: In a large cross-sectional study, children
      aged 7-14 years, with and without documentation and/or scar consistent with BCG
      vaccination, were examined over a period of 2 years and 5 months with the help of
      a questionnaire-based survey followed by skin-prick test (SPT). RESULTS: A total
      of 10,028 children were included. The mean age was 11.04 +/- 2.8 years and M/F
      ratio was 1.1:1. Among them, 77.7% had documentation of BCG vaccination, 17% had
      a BCG-like scar but no documentation and 5.3% had no scar/documentation. SPT was
      performed on 1614 (16%) children. In the BCG group (vaccination and/or scar)
      16.7% were atopic (positive SPT) compared with 21.3% in no BCG (no
      vaccination/scar). The prevalence of allergic diseases among BCG(+) subjects was
      10.1%. Among these, asthma was the commonest one (6.1%), followed by rhinitis
      (3.5%) and eczema (0.5%). There was significant negative correlation between BCG
      positivity, atopy (p = 0.037), and allergic diseases as a whole (p = 0.028), but
      on independent analysis the negative correlation was strongest with allergic
      rhinitis (p = 0.011). CONCLUSION: BCG vaccination is associated with lower
      prevalence of allergic disorders in Indian children.

PMID- 23883803
TI  - The effects of mometasone furoate and desloratadine in obstructive sleep apnea
      syndrome patients with allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) and obstructive sleep apnea syndrome (OSAS)
      are worldwide prevalent diseases. These diseases impair patient quality of life.
      The aim of this study was to investigate and compare the efficacy of treatment of
      AR on OSAS by objective and subjective methods. METHODS: The study group was
      composed of 80 OSAS patients with AR between the ages of 30 and 50 years. The
      patients were admitted with the complaint of snoring, and they were asked about
      AR-related symptoms (nasal discharge, nasal itching, sneeze, and nasal
      obstruction). Daytime somnolence was measured by the Epworth sleepiness scale
      (ESS). Sleep parameters on polysomnography tests before and after treatment were
      compared, and the effects of different AR treatment protocols on sleep quality
      were evaluated. RESULTS: When pretreatment and posttreatment apnea-hypopnea index
      (AHI) values of the groups were compared, the most significant difference was
      observed in the nasal steroid (Ns) + antihistamine (Ah) group (p < 0.05). The ESS
      results were significantly decreased in the Ns and Ns + Ah groups after treatment
      (p < 0.05). AHI oxygen saturation <90% were significantly decreased in the Ns and
      Ns + Ah groups after treatment (p < 0.05). CONCLUSION: Nasal obstruction due to
      nasal congestion causes increases in airway resistance and can lead to
      development of OSAS. We concluded that treating AR with Ns has both positive
      effects on OSAS and daily activity. However, adding Ah to this treatment did not
      show improved effects compared with placebo treatment.

PMID- 23883804
TI  - Unilateral inferior turbinate bone hypertrophy: is it compensatory or congenital?
AB  - BACKGROUND: This study evaluates the degree of the unilateral hypertrophied
      inferior turbinate (HIT) by computed tomography (CT) and determines and compares
      the enlargement of the turbinate bone and soft tissue in different parts of the
      HIT in pediatric and adult groups. METHODS: Both pediatric and adult patients
      were studied in two groups: those with a straight or nearly straight septum (n =
      25 and 124, respectively) and those with deviation (n = 64 and 129,
      respectively). The cross-sectional area (CSA) of the IT bone and soft tissue were
      measured at anterior, middle, and posterior thirds of the IT in coronal CT
      sections. The ratio of CSA of the IT bone and soft tissue on two sides of the
      septum (interturbinate ratio [IR]) were calculated. IRs were then compared among
      straight septum and deviation groups for both the pediatric and the adult groups.
      RESULTS: IR of the bony concha CSA for the deviation group was significantly
      higher compared with the straight septum group in anterior, middle, and posterior
      segments in adults (p = 0.028, 0.018, and <0.001, respectively; independent
      samples t-test). The soft tissue component hypertrophy was prominent only in the
      middle segment (p = 0.15); however, there was no significant difference for
      pediatric patients. Also, there was a statistically significant difference
      between the adult group with septum deviation and the pediatric group with septum
      deviation for both soft tissue and bone components (p < 0.001 for all segments;
      independent samples t-test). CONCLUSION: We claim that these results indicate
      that skeletal and soft tissue IT hypertrophy seem to be compensatory and evolves
      with age rather than being congenital. Therefore, skeletal enlargement is
      prominent in anterior, middle, and posterior thirds of HIT in patients with
      septal deviation in adults but not in the pediatric group.

PMID- 23883806
TI  - Comparison of the nasal release of IL-4, IL-10, IL-17, CCL13/MCP-4, and
      CCL26/eotaxin-3 in allergic rhinitis during season and after allergen challenge.
AB  - BACKGROUND: Allergic rhinitis is an inflammatory disease characterized by local
      overproduction of type 2 cytokines and tissue eosinophilia. Recent research
      suggests the involvement of additional cytokines such as IL-17, chemokine (C-C
      motif) ligand (CCL) 26/eotaxin-3, and CCL13/monocyte chemoattractant protein-4
      (MCP-4) in its pathophysiology. Furthermore, bronchial epithelial cells treated
      with IL-17 and type 2 cytokines distinctively up-regulated eotaxin-3 gene
      expression. In this study we investigated the kinetics of IL-4, IL-10, IL-17,
      eotaxin-3, and MCP-4 in seasonal allergic rhinitis volunteers after nasal
      allergen challenge (NAC) and their release during natural pollen exposure.
      METHODS: The nasal lavages of 15 symptomatic allergic and 14 nonallergic subjects
      were collected during the pollination season. Additionally, six allergic subjects
      underwent a single unilateral nasal allergen and control challenge out of season,
      and nasal secretions were collected. Levels of IL-4, IL-10, IL-17, eotaxin-3, and
      MCP-4 in nasal lavages and secretions were measured using an
      electrochemiluminescent assay. RESULTS: After NAC, allergic subjects had a
      significant immediate response of nasal symptoms as well as a significant
      increase at 5 hours of IL-4, IL-10, and IL-17 and at 2, 5, and 24 hours
      significantly raising levels of eotaxin-3. IL-17 and eotaxin-3 concentrations at
      5 hours were correlated (r = 0.94; p = 0.005). During natural pollen exposure,
      barely detectable levels of IL-17 in allergic subjects were also correlated with
      eotaxin-3 (r = 0.62; p = 0.01). Eotaxin-3 and MCP-4 levels were significantly
      elevated 9- or 3.7-fold, respectively, and IL-10 and, unexpectedly, IL-4 were
      significantly lower in allergic subjects compared with nonallergic subjects.
      CONCLUSION: Nasal IL-17, MCP-4, and, possibly, eotaxin-3 may aggravate and IL-10
      may alleviate nasal mucosal allergy.

PMID- 23883805
TI  - Common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a common primary immunodeficiency
      characterized by a failure in B-cell differentiation with defective
      immunoglobulin production. Affected patients are uniquely susceptible to
      recurrent infection with encapsulated organisms and have an increased propensity
      for the development of inflammatory and autoimmune manifestations. The diagnosis
      of CVID is commonly delayed and the underlying cause of the disorder is not
      understood. Replacement antibody therapy reduces the risk of serious infections.
      However, optimal treatment regimens for the uncommon manifestations associated
      with this disease, such as granulomatous lymphocytic interstitial lung disease,
      require further research. 

PMID- 23883807
TI  - Effect of nasal anti-inflammatory treatment in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Sinonasal inflammation and symptoms are often underdiagnosed in
      chronic obstructive pulmonary disease (COPD) patients. So far, it is not known to
      what extent anti-inflammatory nasal treatment may reduce sinonasal symptoms in
      COPD patients. This study was designed to examine the effects of nasal anti
      inflammatory treatment on sinonasal symptoms and cough in COPD patients. METHODS:
      Thirty-three COPD patients on stable bronchial therapy (salmeterol/fluticasone
      propionate 50/500 mg b.i.d. for >6 weeks) were randomized to receive fluticasone
      furoate (FF) or placebo nasal spray at 110 MUg once daily for 12 weeks. Sinonasal
      symptoms and cough were monitored at baseline, at 6 and12 weeks of treatment, and
      at 4 weeks after cessation of the treatment using a visual analog scale. Levels
      of cytokines were measured in nasal secretions. RESULTS: In contrast to the
      placebo group (n = 13), FF patients (n = 14) reported less nasal blockage (10.62
      +/- 4.21 mm versus 36.57 +/- 8.01 mm; p = 0.0026), postnasal drip (1.46 +/- 0.29
      score versus 2.83 +/- 0.38 score; p = 0.03), and nasal discharge (0.23 +/- 0.12
      score versus 1.77 +/- 0.43 score; p = 0.01) after 6 weeks of treatment compared
      with baseline, which was still present at 12 weeks. FF patients reported less
      cough compared with baseline (25.54 +/- 4.46 mm versus 36.79 +/- 5.75 mm; p =
      0.04), which was not the case in the placebo group (49.58 +/- 10.44 mm versus
      42.00 +/- 8.05 mm; p = 0.38). Nine of 14 patients in the FF group (64%) reported
      slight to total relief of nasal symptoms, and this subgroup had a significant
      decrease in IL-8 levels in nasal secretions after 6 weeks of treatment (850.7 +/-
      207.2 pg/mL versus 1608 +/- 696.5 pg/mL; p = 0.03) compared with baseline.
      CONCLUSION: Nasal FF treatment in COPD patients significantly reduced sinonasal
      symptoms, in parallel with reduced IL-8 in nasal secretion levels and cough.

PMID- 23883808
TI  - Increased expression of high-mobility group protein B1 in chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammation of the sinonasal
      mucosa and many inflammatory cells and cytokines are involved in its
      pathogenesis. High-mobility group protein B1 (HMGB1) is a DNA-binding protein
      that has a proinflammatory function when secreted into extracellular space. The
      purpose of this study was to evaluate the expression of HMGB1 in paranasal sinus
      mucosa and to determine the difference of HMGB1 expression between CRS patients
      and normal controls. METHODS: Paranasal sinus mucosa was obtained from 10
      patients with CRS and 10 patients without CRS. Semiquantitative reverse
      transcriptase-polymerase chain reaction (RT-PCR), real-time PCR and Western blot
      analysis were performed to detect mRNA and protein. Sections of the mucosa were
      immunostained for localization of HMGB1 and image analysis was performed.
      RESULTS: RT-PCR and real-time PCR showed that the expression level of HMGB1 mRNA
      was significantly increased in the tissues of patients with CRS compared with
      controls. Western blot analysis showed that the expression level of HMGB1 protein
      was significantly increased in the tissues of CRS. In immunohistochemical
      staining, the HMGB1 protein was expressed in epithelial cells and inflammatory
      cells and the expression intensity of HMGB1 protein was stronger in CRS.
      CONCLUSION: HMGB1 is increased in the paranasal sinus mucosa of patients with
      CRS. These results suggest a possible contribution of HMGB1 in the
      pathophysiology of CRS.

PMID- 23883809
TI  - The emerging role of the bitter taste receptor T2R38 in upper respiratory
      infection and chronic rhinosinusitis.
AB  - BACKGROUND: Maintaining a clean upper respiratory tract requires efficient
      detection of pathogenic bacteria so that the airway mucosa can mount proper
      defenses to neutralize and clear the offending microbes. Bitter taste receptors
      (T2Rs) may play a critical role in this process. T2Rs were originally identified
      in taste cells of the tongue, where they protect against the ingestion of toxic
      plant and/or bacterial products. However, T2Rs are also expressed in
      extragustatory tissue including the airways. One specific T2R isoform, T2R38, was
      recently shown to be expressed in cilia of sinonasal epithelial cells, suggesting
      that respiratory cilia may function as a chemosensory organelle, possibly to
      detect bacterial presence in the airway. T2R38 is encoded by the TAS2R38 gene,
      which has several common genetic polymorphisms that result in altered receptor
      functionality. Genetic variation in T2R38 may thus contribute to individual
      differences in susceptibility to upper airway infection. This study provides an
      overview of our current knowledge of T2R38 function in sinonasal defense and the
      implications for patients with chronic rhinosinusitis (CRS). METHODS: A
      literature review was performed of the current knowledge of the bitter taste
      receptor T2R38 in sinonasal physiology and CRS patient outcomes. RESULTS: Basic
      science research has indicated that the T2R38 receptor is activated by acyl
      homoserine lactone (AHL) molecules secreted by gram-negative bacteria, including
      Pseudomonas aeruginosa. In sinonasal epithelial cells T2R38 stimulates an
      increase in nitric oxide production that increases mucociliary clearance and
      directly kills bacteria. Recent clinical studies have also found clinical
      correlations of TAS2R38 genotype with susceptibility to gram-negative upper
      respiratory infection as well as necessity for surgical intervention in CRS
      management. CONCLUSION: T2R38 appears to be an important mediator of sinonasal
      epithelial defense, but further study is needed to more clearly determine how
      TAS2R38 genotype affects patient outcomes in CRS and other upper airway diseases.

PMID- 23883810
TI  - Schneiderian papillomas: comparative review of exophytic, oncocytic, and inverted
      types.
AB  - BACKGROUND: Sinonasal papillomas are benign epithelial neoplasms arising from
      Schneiderian mucosa. The three subtypes, exophytic, oncocytic, and inverted
      (inverted papilloma [IP]), should be distinguished from one another
      histopathologically. This study (1) highlights the histopathological and clinical
      differences between the Schneiderian papilloma subtypes and (2) identifies
      clinical features that potentially predict papilloma subtypes. METHODS: A
      retrospective review was performed of patients with Schneiderian papillomas over
      an 11-year period. RESULTS: Seventy patients with sinonasal papillomas who
      underwent sinus surgery were identified. There were 50 (71%) male and 20 (29%)
      female subjects diagnosed at an average age of 53 years (range, 13-80 years).
      Exophytic (n = 25), oncocytic (n = 9), and IP (n = 37) were identified. IP was
      associated with transformation into squamous cell carcinoma in three (8%) cases
      and dysplasia in three (8%) cases. Neither oncocytic nor exophytic subtypes were
      associated with dysplasia or malignancy. On multivariate analysis of potential
      predictors of papilloma subtype, history of chronic rhinosinusitis (CRS) and
      location of papilloma were significantly associated with papilloma subtype. Using
      classification and regression tree model, papilloma subtypes can be predicted
      based on presence or absence of CRS and papilloma location with nominal 82.4%
      accuracy. CONCLUSION: The inverted and exophytic type are the most common
      sinonasal papillomas, with the inverted type having an 8% rate of malignant
      transformation in this study. In contrast, the oncocytic type was not associated
      with dysplasia or malignancy in our series despite reports in the literature
      indicating malignant potential. History of CRS and papilloma location can provide
      clues to the histological subtype, which is important for surgical planning and
      patient counseling.

PMID- 23883811
TI  - Olfactory dysfunction and asthma as risk factors for poor quality of life in
      upper airway diseases.
AB  - BACKGROUND: The study of olfaction/quality of life (QoL) interaction has not been
      adequately discussed and remains to be further explored. Determination of
      clinical predictors for poor QoL may support consultation of respective patients.
      This study explores QoL of patients with olfactory dysfunction and evaluates
      associated clinical risk factors for QoL prediction. METHODS: One hundred eight
      patients suffering from chronic rhinosinusitis (CRS) and allergic rhinitis (AR)
      and 30 healthy subjects were studied. Olfactory function was evaluated using
      objective olfactory test. All patients completed six validated questionnaires
      either specific for olfaction (Questionnaire of Olfactory Deficits [QOD]) and for
      assessing psychological state (Zung Anxiety Scale [ZAS], State-Trait Anxiety
      Inventory, Zung Depression Scale, and Beck Depression Inventory [BDI]) or a
      generic one (Short Form 36). RESULTS: Significantly poorer QoL and more severe
      anxiety and depression symptoms were observed in anosmic (all p < 0.001) and
      hyposmic patients compared with controls. Anosmic patients presented
      significantly worse results compared with hyposmic and normosmic patients.
      However, higher scores were observed in hyposmic compared with normosmic patients
      only in the QOD, ZAS, and BDI scale. Patients with CRS presented significantly
      poorer QoL than patients with AR only. The presence of nasal polyps or
      concomitant AR in patients with CRS did not show any differentiation in the
      results. Asthma was associated with significantly worse scores in all the
      psychometric questionnaires. CONCLUSION: Olfactory dysfunction was found to
      decrease QoL among patients. Anosmia, CRS disease, and asthma as clinical
      predictors were proved to be independently correlated with QoL, anxiety, and
      depression levels.

PMID- 23883812
TI  - Randomized double-blind placebo-controlled crossover study of efficacy of pollen
      blocker cream for perennial allergic rhinitis.
AB  - BACKGROUND: This study evaluates the efficacy and safety of a pollen blocker
      cream in treatment of perennial allergic rhinitis (PAR) in a Chinese population.
      METHODS: A randomized double-blind placebo-controlled, crossover trial was
      conducted in the Outpatient Department of the Eye, Ear, Nose, and Throat
      Hospital, Fudan University, Shanghai, China. Patients diagnosed with PAR were
      randomly assigned to receive pollen blocker cream or placebo, which was applied
      and evenly distributed to the lower internal nose region three times daily for a
      total of 30 days. The primary outcome measures for efficacy were nasal symptom
      scores (NSSs) and quality of life scores (QoLSs). Medication scores and adverse
      events were also monitored. RESULTS: After application of pollen blocker, the
      mean NSS fell from 23.1 to 12.4 points, and the QoLSs fell from 83.9 to 53.2
      points (p < 0.001). The decrease in NSSs of pollen blocker (10.7) was highly
      significant compared with the placebo (3.6; p < 0.001). The decrease in QoLSs of
      pollen blocker was 30.7 compared with 7.1 in the placebo group, and the
      difference was also significant (p < 0.05). Interestingly, the mean NSS of the
      placebo group also decreased from 23.7 to 20.1 (p < 0.05). Additionally, the
      efficacy of pollen blocker was superior to the placebo both in adults and in
      children. However, there was no significant difference for individual symptoms of
      rhinorrhea, nasal itching, sneezing, and nasal congestion between the pollen
      blocker group and placebo group (p > 0.05). Only one mild epistaxis was reported.
      CONCLUSION: The pollen blocker was significantly more effective than the placebo
      in relieving allergy symptoms and improving life quality of PAR in 30 Chinese
      people.

PMID- 23883813
TI  - Technical feasibility of endoscopic eustachian tube catheter placement: a
      cadaveric analysis.
AB  - BACKGROUND: Patulous eustachian tube (pET) can result in transmission of sound
      from the pharynx to the middle ear (ME) via an abnormally patent ET. The
      objective of this study was to evaluate the technical feasibility of a reversible
      transnasal procedure for pET using an occluded silastic catheter to close the ET.
      METHODS: Ten sides were evaluated in five cadaver heads. Size 14, 16, and 18G
      catheters were occluded with bone wax to create a semirigid solid tube. They were
      placed transnasally, under endoscopic guidance through the ET orifice to span the
      entire ET length. Proper placement in the ME was confirmed by tympanotomy. Each
      attempt was graded on a four-point scale based on ease of placement: 3+, 2+, 1+,
      and 0. RESULTS: The 16G was the easiest to place with the best fit and was
      confirmed in the ME in eight cases. The 14G catheter was next easiest to place
      and was observed in the ME in seven cases. It generally had an extremely tight
      fit and propensity to impart mucosal trauma. The 18G was the most difficult to
      place and was observed in the ME in six cases. The catheter was noted to displace
      easily because of a loose fit. Tympanic membrane or ossicular injury was not
      noted in any trial. CONCLUSION: These cadaveric data suggest that a semirigid
      catheter provides the technical capability to reversibly occlude the ET via the
      transnasal endoscopic route. Further confirmation is necessary in human studies
      to determine its effectiveness for management of pET.

PMID- 23883814
TI  - Does surgery of the olfactory clefts modify the sense of smell?
AB  - BACKGROUND: The olfactory outcome after surgery of polyps in the olfactory clefts
      (OCs) is unknown. This study was designed to (1) investigate the relationship
      between clinical characteristics and the presence of the respiratory epithelial
      adenomatoid hamartoma (REAH) in the OCs and (2) assess the olfactory outcome
      after surgery in the OC for either eosinophilic polyps (EP) or REAH in patients
      with ethmoidectomy for nasal polyposis (NP). METHODS: Seventy-four patients with
      NP having undergone nasalization procedure were enrolled in this prospective
      study. The OCs were systematically examined during endoscopic surgery. Small
      polyps or edematous mucosa of the OC were systematically biopsied. Moderate or
      big polyps in the OC were removed after nasalization of the ethmoidal labyrinths.
      The distinction between REAH and EP relied on histopathological examinations. The
      olfactory function was measured with standardized odor threshold and
      identification tests 1 day before and 6 weeks after surgery. RESULTS: There was a
      close relationship between the presence of REAH-OC and the duration of NP disease
      (p = 0.0009), asthma (p = 0.004), and previous surgery (p = 0.0006). Before
      surgery, 90.6% of patients with REAH-OC were hypo-anosmic in contrast with one
      half of patients having EP-OC (p = 0.0003). Predictors of poor olfactory outcomes
      after surgery were long-standing nasal symptoms (p = 0.027), history of previous
      surgery (p = 0.01), and history of previous middle turbinates resection (p =
      0.0006). Polyp histology and surgery of the OC were not predictors of poor
      olfactory outcomes. CONCLUSION: The resection of REAH or EP of the OC in patients
      with NP does not worsen but instead can improve the sense of smell after surgery.

PMID- 23883815
TI  - Sinonasal respiratory epithelial adenomatoid hamartomas: series of 51 cases and
      literature review.
AB  - BACKGROUND: Respiratory epithelial adenomatoid hamartomas (REAHs) are rare,
      benign glandular proliferations of the nasal cavity, paranasal sinuses, and
      nasopharynx. This study aimed to expand our understanding of this entity by
      presenting a series of REAHs combined with a review of the pertinent literature.
      METHODS: A retrospective review was performed on all patients with a diagnosis of
      REAH from 2002 to 2011. Data were collected with respect to age, gender, clinical
      presentation, imaging, histopathology, treatment, and outcome. Because olfactory
      cleft expansion by imaging evaluation has been reported to suggest REAH, maximum
      olfactory cleft (MOCs) widths were also measured. RESULTS: Fifty-one cases of
      REAH included 37 male (72.5%) and 14 female subjects (27.5%) with a mean age of
      58.4 years. Headache, nasal obstruction, rhinorrhea, and hyposmia were the most
      common presenting symptoms. Although 35(68.6%) were associated with concurrent
      inflammatory pathology, 16 (31.4%) presented as isolated lesions of the nasal
      cavity. Enlargement of MOCs was evident on computed tomography, with mean MOCs of
      8.64 and 9.4 mm, in the coronal/axial planes, respectively. There were no
      statistically significant differences between MOCs of isolated (7.96 mm) versus
      MOCs of associated (9.63 mm) lesions (p = 0.25). Forty-nine were treated with
      endoscopic resection without evidence of recurrence after a mean follow-up of
      27.2 months. CONCLUSION: REAHs are rare sinonasal lesions that may appear as
      localized, isolated masses or more diffuse when in conjunction with other
      inflammatory processes. Irrespective of clinical presentation, endoscopic removal
      appears to be curative. Differentiation from more aggressive lesions is paramount
      to avoid unnecessarily radical surgery for an otherwise benign process.

PMID- 23883816
TI  - Efficacy of targeted middle meatal antibiotics and endoscopic sinus surgery.
AB  - BACKGROUND: Postoperative infection remains a significant comorbidity of
      endoscopic sinus surgery (ESS) delayed healing, synechia formation, etc. The
      objective of this study was to compare the incidence of postoperative infection
      after ESS in patients receiving conventional postoperative oral antibiotic
      prophylaxis versus a synthetic bioabsorbable antibiotic-soaked nasal sponge used
      in the middle meatus (MM) in lieu of oral antibiotics. METHODS: A prospective
      randomized multicenter trial included 321 chronic rhinosinusitis patients
      undergoing minimally invasive ESS who received either 1 week of oral antibiotics
      and a saline-soaked bioabsorbable MM sponge (control group) or no oral
      antibiotics and the placement of a bacitracin-soaked bioabsorbable sponge in the
      MM (study group). Evaluations performed at baseline, 3-weeks, and 3-months
      postoperatively included the 20-item Sino-Nasal Outcome Test and nasal endoscopic
      examination. RESULTS: The 3-week postoperative infection rate was not
      significantly different between the study (n = 165) and control groups (n = 156):
      5.4% versus 3.8%; p > 0.05. In addition, there was no significant difference
      between the two patient groups on evaluation of MM granulations, synechia, middle
      turbinate lateralization, or sponge retention. CONCLUSION: Antibiotic-soaked
      synthetic bioabsorbable MM sponges show equivalent efficacy in controlling post
      ESS infections compared with conventional postoperative oral antibiotics. Topical
      antibiotic delivery to the MM via bioabsorbable sponges may reduce the need for
      postoperative systemic antibiotics and provide a cost-effective alternative that
      eliminates the issues of antibiotic side effects, drug-drug interactions, and
      medication compliance in the postoperative setting.

PMID- 23883817
TI  - Polyhydrated ionogen with MgBr2 accelerates in vitro respiratory epithelial
      healing.
AB  - BACKGROUND: Remucoslization of the sinonasal cavity after sinus surgery is
      critical for successful outcomes. Recently, a novel antiprotease and
      antifibroblast compound, polyhydrated ionogen (PHI) with MgBr2, showed improved
      wound healing in a rabbit maxillary sinus mucosal wound model. We set out to
      determine if this effect was reproducible in an in vitro respiratory epithelial
      culture system. METHODS: Fully differentiated mature murine nasal septal air
      liquid interface cultures were injured by creating a full-thickness 400-mM-wide
      scratch through the monolayer. Cultures were then treated with nothing, saline,
      or PHI with MgBr2 for 1 hour on the apical surface. Twenty-four hours after the
      injury cultures were fixed and processed for immunofluorescence with type IV beta
      tubulin and Hoechst stain. RESULTS: Initial injury resulted in a wound of 394
      micromolar (377-411 micromoler; 95% CI; n = 8). After 24 hours with no
      intervention the wound closed to 161 micromolar (138-184 micromolar; 95% CI; n =
      9) and treatment with saline resulted in a residual gap of 88 micromolar (60-116
      micromolar; 95% CI; n = 9; p < 0.05) and treatment with PHI with MgBr2 resulted
      in a gap of only 30 micromolar (14-46 micromolar; 95% CI; n = 9; p < 0.05).
      CONCLUSION: Poor healing of the sinonasal mucosa after surgery with loss of
      ciliary function results in adverse clinical outcomes. In an in vitro sinonasal
      respiratory epithelial injury model, a one-time treatment with PHI with MgBr2
      showed significantly improved wound healing compared with saline or nothing. This
      is a viable model to further investigate the mechanism by which PHI with MgBr2
      improves sinonasal remucosolization.

PMID- 23883819
TI  - Estradiol downregulates NF-kappab translocation by Ikbkg transcriptional
      repression in dendritic cells.
AB  - To reconcile immunity and reproduction, females must allow spermatozoa to survive
      and control the presence of commensal microbiota and sexually transmitted
      pathogens during ovulation. Female steroid sex hormones exert a powerful effect
      on the immune system, as do the hormonal changes associated with the ovarian
      cycle. Dendritic cells (DCs) are immunological sentinels that link innate
      immunity to adaptive immunity. Upon exposure to microbial invaders in tissue,
      they undergo a maturational process that culminates in the lymph nodes and
      activates T-cell-specific immune responses. Estradiol, which is highly expressed
      during ovulation, has an effect on the maturation of DCs, although the molecular
      mechanism remains elusive. We detected that estradiol regulates expression of
      Ikbkg in DCs and modulates nuclear factor-kappab translocation to the nucleus,
      thus explaining the reduced DC function observed during ovulation. This change
      may be an adaptive mechanism to reconcile control of infection and reproductive
      functions. 

PMID- 23883820
TI  - Magnetic resonance identification of hydrogen at a zinc vacancy in ZnO.
AB  - Hydrogen (H) at a zinc vacancy (VZn) in ZnO is identified by electron
      paramagnetic resonance (EPR) and electron spin echo envelope modulation (ESEEM).
      In ZnO irradiated by 2 MeV electrons, a doublet EPR spectrum, labelled S1, is
      observed. The doublet structure and the accompanying weak satellites are shown to
      be the allowed and forbidden lines of the hyperfine structure due to the dipolar
      interaction between an electron spin S = 1/2 and a nuclear spin I = 1/2 of (1)H
      located at a VZn. The involvement of a single H atom in the S1 defect is further
      confirmed by the observation of the nuclear Zeeman frequency of (1)H in ESEEM
      experiments. We show that at a VZn, H prefers to make a short O-H bond with one O
      neighbour and is off the substitutional site, forming a low symmetry C1 defect.
      In this partly H passivated VZn, the unpaired electron localizes on the p orbital
      of another O neighbour of VZn, and not on the H. 

PMID- 23883822
TI  - Identification and characterization of microRNAs in Baylisascaris schroederi of
      the giant panda.
AB  - BACKGROUND: Baylisascaris schroederi is one of the most significant threats to
      the giant panda's survival, responsible for half of the deaths reported from 2001
      to 2005. MicroRNA (miRNA) has been identified as one of the key factors for gene
      regulations at the post-transcriptional level, and also considered as a potential
      control and treatment target against infectious diseases. METHODS: The present
      study investigated the miRNA profile of B. schroederi via high throughput
      sequencing and real-time quantitative PCR. RESULTS: A total of 18.07 million raw
      reads were obtained and 18.01 million were identified with high quality. By
      analysis of standard stem-loop structures, 108 miRNA candidates were predicted,
      including 60 known miRNAs and 48 novel ones. Target prediction revealed that the
      "chitinase" was the most abundant target with 483 sequences, and 263 targets were
      related to ovarian and egg development. The ribosomal protein related sequences
      occupied 449 sequences. CONCLUSIONS: Previous studies have shown that some
      parasites secrete chitinases for exsheathment and/or for penetrating the
      peritrophic matrix of the host. It therefore seems that B. schroederi may be
      effectively regulated by miRNAs for development, invasion, and reproduction.
      Given that chitinases have been identified as important biological control agents
      for pests, identification of microRNAs in B. schroederi of the giant panda would
      provide useful information for the development of biological control strategies
      and/or vaccines against B. schroederi infection in the giant panda.

PMID- 23883823
TI  - Arterial stiffness response to exercise in persons with and without Down
      syndrome.
AB  - This study compared arterial stiffness and wave reflection at rest and following
      maximal exercise between individuals with and without Down syndrome (DS), and the
      influence of body mass index (BMI), peak oxygen uptake (VO2 peak) on changes in
      arterial stiffness. Twelve people with DS (26.6 +/- 2.6 yr) and 15 healthy
      controls (26.2 +/- 0.6 yr) completed this study. Intima-media thickness (IMT) and
      stiffness of common carotid artery was examined. Hemodynamic and arterial
      variables were measured before and 3-min after exercise. Persons with DS had
      higher BMI and lower VO 2 peak than controls. IMT did not differ between groups.
      At rest, carotid beta stiffness was significantly higher in persons with DS
      (P<0.05) but there was no difference in between groups for any of the other
      arterial stiffness measures. After exercise, persons with DS exhibited attenuated
      arterial stiffness responses in AIx-75, carotid beta stiffness and Ep in contrast
      with controls (significant group-by-time interactions). When controlling for BMI
      and VO 2 peak, the interactions disappeared. In both groups combined, BMI was
      correlated significantly with carotid Ep and beta at rest. VO 2 peak correlated
      significantly with AIx-75 and its pre-post change (r=-0.45, P=0.029; r=0.47,
      P=0.033, respectively). The arterial stiffness responses to maximal exercise in
      persons with DS were blunted, potentially reflecting diminished vascular reserve.
      Obesity and particularly VO 2 peak influenced these findings. These results
      suggest impaired vascular function in people with DS.

PMID- 23883821
TI  - Glycovariant anti-CD37 monospecific protein therapeutic exhibits enhanced
      effector cell-mediated cytotoxicity against chronic and acute B cell
      malignancies.
AB  - TRU-016 is a SMIP(TM) (monospecific protein therapeutic) molecule against the
      tetraspanin transmembrane family protein CD37 that is currently in Phase 2 trials
      in Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL). In an
      attempt to enhance the ADCC function of SMIP-016, the chimeric version of TRU
      016, SMIP-016(GV) was engineered with a modification in a glycosylation site in
      the Fc domain. The wild-type and glycovariant SMIP proteins mediate comparable
      Type I antibody-like direct cytotoxicity in the presence of anti-human Fc
      crosslinker and show a similar tyrosine phosphorylation pattern post-treatment.
      However, NK cells stimulated with the SMIP-016(GV) exhibit enhanced activation
      and release 3-fold more interferon-gamma compared with SMIP-016. SMIP-016(GV)
      shows enhanced ADCC function against cells expressing CD37 with NK cell effectors
      derived from both normal and CLL-affected individuals. Enhanced ADCC is observed
      against CLL cells and is sustained at concentrations of SMIP-016(GV) as low at
      5E(-6) ug/mL on cells expressing minimal CD37 antigen. In support of the
      biological relevance of this, SMIP-016(GV) mediates effective ADCC against
      primary acute lymphoblastic leukemia (ALL) cells with low surface expression of
      CD37. Collectively, these data suggest potential use of the novel therapeutic
      agent SMIP-016(GV) with enhanced effector function for B cell malignancies,
      including CLL and ALL therapy. 

PMID- 23883824
TI  - Risk of cancer after lumbar fusion surgery with recombinant human bone
      morphogenic protein-2 (rh-BMP-2).
AB  - STUDY DESIGN: Retrospective cohort study among Medicare beneficiaries with lumbar
      spinal fusion surgery. OBJECTIVE: To determine the risk of subsequent cancer
      among patients who received recombinant human bone morphogenic protein (rhBMP) at
      surgery compared with those who did not. SUMMARY OF BACKGROUND DATA: rhBMP is
      commonly used to promote bone union after spinal surgery. BMP receptors are
      present on multiple cancer types, but the risk of cancer after receiving rhBMP
      has not been well studied. METHODS: We identified 146,278 subjects aged 67 years
      and older who underwent surgery in 2003 to 2008 and were followed through 2010
      for a new diagnosis of 1 of 26 cancers. Proportional hazards models were used to
      determine cancer risk associated with rhBMP use. RESULTS: rhBMP was administered
      in 15.1% of the cohort. After an overall average follow-up of 4.7 years, 15.4% of
      rhBMP-treated and 17.0% of untreated patients had a new cancer diagnosis, with
      most commonly recorded types as prostate, breast, lung, and colorectal. In a
      multivariate proportional hazards model, there was no association of rhBMP with
      cancer risk (hazard ratio: 0.99, 95% confidence interval: 0.95-1.02). There was
      also no association of rhBMP with the risk of any individual cancer types. The
      results were consistent in analyses using 2 secondary definitions of incident
      cancer. CONCLUSION: In this large population-based analysis of Medicare
      beneficiaries, we found no evidence that administration of rhBMP at the time of
      lumbar fusion surgery was associated with cancer risk. LEVEL OF EVIDENCE: 4.

PMID- 23883825
TI  - Indian hedgehog signaling promotes chondrocyte differentiation in enchondral
      ossification in human cervical ossification of the posterior longitudinal
      ligament.
AB  - STUDY DESIGN: Histological, immunohistochemical, and immunoblot analyses of the
      expression of Indian hedgehog (Ihh) signaling in human cervical ossification of
      the posterior longitudinal ligament (OPLL). OBJECTIVE: To examine the hypothesis
      that Ihh signaling in correlation with Sox9 and parathyroid-related peptide
      hormone (PTHrP) facilitates chondrocyte differentiation in enchondral
      ossification process in human cervical OPLL. SUMMARY OF BACKGROUND DATA: In
      enchondral ossification, certain transcriptional factors regulate cell
      differentiation. OPLL is characterized by overexpression of these factors and
      disturbance of the normal cell differentiation process. Ihh signaling is
      essential for enchondral ossification, especially in chondrocyte hypertrophy.
      METHODS: Samples of ossified ligaments were harvested from 45 patients who
      underwent anterior cervical decompressive surgery for symptomatic OPLL, and 6
      control samples from patients with cervical spondylotic myelopathy/radiculopathy
      without OPLL. The harvested sections were stained with hematoxylin-eosin and
      toluidine blue, examined by transmission electron microscopy, and
      immunohistochemically stained for Ihh, PTHrP, Sox9, type X, XI collagen, and
      alkaline phosphatase. Immunoblot analysis was performed in cultured cells derived
      from the posterior longitudinal ligaments in the vicinity of the ossified plaque
      and examined for the expression of these factors. RESULTS: The ossification front
      in OPLL contained chondrocytes at various differentiation stages, including
      proliferating chondrocytes in fibrocartilaginous area, hypertrophic chondrocytes
      around the calcification front, and apoptotic chondrocytes near the ossified
      area. Immunoreactivity for Ihh and Sox9 was evident in proliferating chondrocytes
      and was strongly positive for PTHrP in hypertrophic chondrocytes. Mesenchymal
      cells with blood vessel formation were positive for Ihh, PTHrP, and Sox9.
      Cultured cells from OPLL tissues expressed significantly higher levels of Ihh,
      PTHrP, and Sox9 than those in non-OPLL cells. CONCLUSION: Our results indicated
      that overexpression of Ihh signaling promotes abnormal chondrocyte
      differentiation in enchondral ossification and enhances bone formation in OPLL.

PMID- 23883826
TI  - Iatrogenic consequences of early magnetic resonance imaging in acute, work
      related, disabling low back pain.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the effect of
      early (receipt <=30 d postonset) magnetic resonance imaging (MRI) on disability
      and medical cost outcomes in patients with acute, disabling, work-related low
      back pain (LBP) with and without radiculopathy. SUMMARY OF BACKGROUND DATA:
      Evidence-based guidelines suggest that, except for "red flags," MRI is indicated
      to evaluate patients with persistent radicular pain, after 1 month of
      conservative management, who are candidates for surgery or epidural steroid
      injections. Prior research has suggested an independent iatrogenic effect of
      nonindicated early MRI, but it had limited clinical information and/or patient
      populations. METHODS: A nationally representative sample of workers with acute,
      disabling, occupational LBP was randomly selected, oversampling those with
      radiculopathy diagnoses (N = 1000). Clinical information from medical reports was
      used to exclude cases for which early MRI might have been indicated, or MRI
      occurred more than 30 days postonset (final cohort = 555). Clinical information
      was also used to categorize cases into "nonspecific LBP" and "radiculopathy"
      groups and further divided into "early-MRI" and "no-MRI" subgroups. The Cox
      proportional hazards model examined the association of early MRI with duration of
      the first episode of disability. Multivariate linear regression models examined
      the association with medical costs. All models adjusted for demographic and
      medical severity measures. RESULTS: In our sample, 37% of the nonspecific LBP and
      79.9% of the radiculopathy cases received early MRI. The early-MRI groups had
      similar outcomes regardless of radiculopathy status: much lower rates of going
      off disability and, on average, $12,948 to $13,816 higher medical costs than the
      no-MRI groups. Even in a subgroup with relatively minimal disability impact (<=30
      d of total lost time post-MRI), medical costs were, on average, $7643 to $8584
      higher in the early-MRI groups. CONCLUSION: Early MRI without indication has a
      strong iatrogenic effect in acute LBP, regardless of radiculopathy status.
      Providers and patients should be made aware that when early MRI is not indicated,
      it provides no benefits, and worse outcomes are likely. LEVEL OF EVIDENCE: 3.

PMID- 23883827
TI  - Prevalence of postoperative pain in adolescent idiopathic scoliosis and the
      association with preoperative pain.
AB  - STUDY DESIGN: Review of a prospective database registry of surgical patients with
      adolescent idiopathic scoliosis (AIS). OBJECTIVE: The purpose of this study was
      to examine the prevalence of postoperative pain and its impact on patient
      reported postoperative outcomes using the Scoliosis Research Society (SRS)-22
      outcomes questionnaire. SUMMARY OF BACKGROUND DATA: Although reportedly rare,
      postoperative pain can be a devastating situation for the patient with AIS. Most
      recent studies examining outcomes in AIS surgical treatment use the SRS Pain
      domain score to assess pain in this population. METHODS: A prospectively enrolled
      multicenter database was queried. Patients with minimum 2-year follow-up and 2
      year SRS scores were included. Postoperative pain after the acute phase of
      recovery when reported by the patient to the treating surgeon/clinical team in
      follow-up is recorded as a complication in the database. Patients included in
      this series were grouped as either reporting pain or not to the surgeon/clinical
      team postoperatively. Pre- and postoperative SRS scores were then compared
      between these 2 groups using analysis of variance (P < 0.05). RESULTS: Five
      hundred and eighty-four patients meeting the inclusion criteria were identified.
      Sixty-one (11%) reported pain at sometime between 2 weeks and 2 years
      postoperatively. Thirteen were within the 6-month postoperative period. Of the
      remaining 48 reporting pain between 6 and 24 months postoperatively, 41 (7% of
      the total cohort) had no obvious cause for their pain. More than half of these
      patients (26/41) were referred for further treatment (physical therapy, referral
      to pain specialist, further imaging). These 41 patients had significantly
      decreased 2-year SRS scores in the domains of Pain, Self-image, Mental health,
      and Total score (P < 0.05). The patients with postoperative pain were found to
      have significantly lower preoperative Pain domain scores (P < 0.001), indicative
      of greater pain preoperatively, yet there were no other domains effected
      preoperatively. For this group the pre- to postoperative SRS pain scores did not
      show significant change (P > 0.05). CONCLUSION: Unexplained pain after the 6
      month postoperative period occurred in 7% of the cohort. The results indicate
      that patients reporting pain to their surgeons/clinical team postoperatively have
      lower pain scores on a subjective outcome instrument thus further validating the
      SRS-22 outcome tool. This reported pain seems to be associated with decreases in
      other SRS-22 domains. Interestingly, these patients also have lower preoperative
      pain scores than those without postoperative pain. Study into causes of pain in
      AIS and whether preoperative education and expectations targeted at this
      population would positively impact outcomes is warranted, especially because on
      average patients after AIS surgery have less pain. LEVEL OF EVIDENCE: 3.

PMID- 23883828
TI  - Comparison of dysphagia between cervical artificial disc replacement and fusion:
      data from a randomized controlled study with two years of follow-up.
AB  - STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To determine
      and explain any differences in self-reported dysphagia between patients treated
      with artificial disc replacement and anterior cervical decompression and fusion
      (ACDF). SUMMARY OF BACKGROUND DATA: Dysphagia after anterior cervical spine
      surgery has in previous studies been evaluated regarding different influencing
      factors. Surgical technique, number of treated levels, and type of implant has
      been shown to be of possible importance. METHODS: One hundred thirty-six patients
      from a randomized controlled trial between artificial disc replacement and ACDF
      in 1 or 2 surgical levels were evaluated regarding dysphagia. Evaluation was done
      with the dysphagia short questionnaire preoperatively, at 4 weeks, 3 months, and
      1 and 2 years postoperatively. Reconstruction in the artificial disc replacement
      group was performed with the Discover artificial disc. Bone graft and anterior
      plating was used in the ACDF group. Type of implant was blinded to the patients
      and the surgeon until time of implantation. RESULTS: Demographics and dysphagia
      short questionnaire levels were similar in both groups preoperative. At 4 weeks
      of follow-up postoperatively, dysphagia was significantly higher in both groups
      than baseline levels, P < 0.01. No significant differences were seen between the
      groups until follow-up at 2 years, which showed significantly higher dysphagia
      short questionnaire levels in the ACDF group, P = 0.04. The difference was
      statistically significant in both patients treated with 1- and 2-level surgery, P
      = 0.029 and P = 0.032, respectively. A logistic regression model showed a
      stronger association to type of implant than to number of surgical levels.
      Duration of surgery was highly associated to number of surgical levels but did
      not differ significantly between types of implant. CONCLUSION: Long-term
      postoperative dysphagia could be explained by bulk of implant or decreased motion
      in the cervical spine. However, it is doubtful if differences between the groups
      in this study can be interpreted as a clinically important difference. LEVEL OF
      EVIDENCE: 2.

PMID- 23883830
TI  - Intraoperative cone beam-computed tomography with navigation (O-ARM) versus
      conventional fluoroscopy (C-ARM): a cadaveric study comparing accuracy,
      efficiency, and safety for spinal instrumentation.
AB  - STUDY DESIGN: Cadaveric laboratory study. OBJECTIVE: To compare the accuracy,
      efficiency, and safety of intraoperative cone beam-computed tomography with
      navigation (O-ARM) with traditional intraoperative fluoroscopy (C-ARM) for the
      placement of pedicle screws. SUMMARY OF BACKGROUND DATA: Radiation exposure
      remains a concern with traditional methods of intraoperative imaging in spine
      surgery. The use of O-ARM has been proposed for more accurate and efficient
      spinal instrumentation. Understanding radiation imparted to patients and surgeons
      by O-ARM is important for assessing risks and benefits of this technology,
      especially in light of evolving indications. METHODS: Four surgeons placed 160
      pedicle screws on 8 cadavers without deformity. Eighty pedicle screws were placed
      using O-ARM and C-ARM each. Instrumentation was placed bilaterally in the
      thoracic (T1-T6) spine and lumbosacral junction (L5-S1) using a standard open
      technique, whereas minimally invasive surgery technique was used at the lumbar 3
      to 4 (L3-L4) level. A "postoperative" computed tomography (CT) scan was performed
      on cadavers where instrumentation was done using the C-ARM. An independent
      musculoskeletal radiologist assessed final images for screw position. Time
      required to set up and instrumentation was recorded. Dosimeters were placed on
      multiple aspects of cadavers and surgeons to record radiation exposure. RESULTS:
      There were no differences in breach rate between the O-ARM and C-ARM groups (5
      vs. 7, chi= 0.63, P = 0.4). The setup time for the O-ARM group was longer than
      that for the C-ARM group (592 vs. 297 s, P < 0.05). However, the average total
      time was statistically the same (1629 vs. 1639 s, P = 0.96). Radiation exposure
      was higher for surgeons in the C-ARM group and cadavers in the O-ARM group. When
      a "postoperative" CT scan was included in the estimation of the total radiation
      exposure, there was less of difference between the groups, but still more for the
      O-ARM group. CONCLUSION: In cadavers without deformity, O-ARM use results in
      similar breach rates as C-ARM for the placement of pedicle screws. Time for
      instrumentation is shorter with the O-ARM, but requires a longer setup time. The
      O-ARM exposes less radiation to the surgeon, but higher doses to the cadaver.
      LEVEL OF EVIDENCE: N/A.

PMID- 23883829
TI  - CHD7 gene polymorphisms and familial idiopathic scoliosis.
AB  - STUDY DESIGN: Model-independent linkage analysis and tests of association were
      performed for 22 single nucleotide polymorphisms in the CHD7 gene in 244 families
      of European descent with familial idiopathic scoliosis (FIS). OBJECTIVE: To
      replicate an association between FIS and the CHD7 gene on 8q12.2 in an
      independent sample of families of European descent. SUMMARY OF BACKGROUND DATA:
      The CHD7 gene on chromosome 8, responsible for the CHARGE syndrome, was
      previously associated with FIS in an independent study that included 52 families
      of European descent. METHODS: Model-independent linkage analysis and
      intrafamilial tests of association were performed on the degree of lateral
      curvature considered as a qualitative trait (with thresholds of >=10 degrees ,
      >=15 degrees , >=20 degrees , and >=30 degrees ) and as a quantitative trait
      (degree of lateral curvature). Results from the tests of associations from this
      study and the previous study were combined in a weighted meta-analysis. RESULTS:
      No significant results (P < 0.01) were found for linkage analysis or tests of
      association between genetic variants of the CHD7 and FIS in this study, failing
      to replicate the findings from the previous study. Furthermore, no significant
      results (P < 0.01) were found from meta-analysis of the results from the tests of
      association from this sample and from the previous sample. CONCLUSION: No
      association between the 22 genotyped single nucleotide polymorphisms in the CHD7
      gene and FIS within this study sample was found, failing to replicate the earlier
      findings. Further investigation of the CHD7 gene and its potential association to
      FIS may be required. LEVEL OF EVIDENCE: N/A.

PMID- 23883831
TI  - Recovery room radiographs not found to have incremental utility above
      intraoperative images after lumbar fusion procedures.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize the clinical
      utility of imaging in the recovery room after lumbar fusion procedures. SUMMARY
      OF BACKGROUND DATA: Two sets of images are commonly obtained at the end of lumbar
      fusion procedures: intraoperative fluoroscopic images near the time of wound
      closure and plain film images after the procedure in the recovery room. The
      latter may have low clinical utility. METHODS: We identified a consecutive series
      of lumbar fusion procedures. A panel of 3 reviewers assessed intraoperative and
      recovery room series both for radiographical adequacy and for issues with the
      surgical construct. RESULTS: One hundred ninety cases were reviewed, of which 92
      were posterolateral lumbar fusions, 42 were anterior lumbar interbody fusions, 24
      were transforaminal lumbar interbody fusions, and 32 were anterior-posterior
      fusions. All intraoperative series were adequate, whereas only 90% of recovery
      room series were adequate. Recovery room series had visible issues with construct
      placement in 4 cases. In each of these cases, however, the issue was also clearly
      visible on the intraoperative series, was found to be acceptable clinically, and
      did not alter management in any way. CONCLUSION: This study demonstrates that
      recovery room images are inferior to intraoperative images and offer little or no
      incremental clinical utility for detecting issues with surgical constructs after
      lumbar fusion procedures. In settings where it is still performed, recovery room
      imaging might be discontinued to realize savings in cost, radiation exposure, and
      time. LEVEL OF EVIDENCE: 4.

PMID- 23883832
TI  - Anomalous vertebral artery injured during anterior cervical discectomy: a case
      report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe treatment and injury prevention
      from discectomy with a newly described vertebral artery anomaly. SUMMARY OF
      BACKGROUND DATA: Cervical segment vertebral artery (VA) anomalies of various
      types are described with the least common type involving erosion into the
      vertebral body medial to the uncinate process. The morphology of these includes
      return to the lateral position at the disc level where they have been immune to
      anterior cervical discectomy surgery. This case report demonstrates the first
      published account of a medial vertebral artery adjacent to a disc and injured by
      discectomy alone.VA injury is a serious complication with a significant
      percentage of neurological injury and death. The lesion was missed by a
      neuroradiologist reading the thin slice preoperative magnetic resonance imaging
      (MRI) study. Subsequently, 6 additional specialists blinded to the study all
      missed the diagnosis. The difficulty of diagnosis is similar to another study
      where 6 neuroradiologists missed 100% of diagnosis of similar lesions on 49 MRI
      studies. METHODS: A 55-year-old female with left-sided weakness in the neck and
      shoulder and C5-C6 stenosis underwent anterior cervical microdiskectomy. When a
      fine-tipped drill bit was used to smoothen a slight convexity on the C6 endplate,
      high pressure and volume hemorrhage started. After tamponade, the patient was
      brought directly to angiography and CT scanning. Several days later, the patient
      underwent endovascular evaluation and stenting for a pseudoaneurysm. RESULTS: No
      neurological deficits occurred from the complication. Cervical discomfort and
      headache symptoms partially improved. CONCLUSION: A previously undescribed medial
      vertebral artery anomaly involving the cervical disc level is documented with
      near disastrous hemorrhage from simple anterior discectomy. The rate of
      preoperative diagnosis from MRI scans is dismal. Preoperative studies should be
      scrutinized with suspicion and any questionable area studied further regardless
      of a negative diagnosis. LEVEL OF EVIDENCE: N/A.

PMID- 23883833
TI  - Ossification of the posterior longitudinal ligament in not only the cervical
      spine, but also other spinal regions: analysis using multidetector computed
      tomography of the whole spine.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: To evaluate ossification of
      the posterior longitudinal ligament (OPLL) of the whole spine in patients with
      cervical OPLL and to analyze which types of cervical OPLL were associated with
      the other lesions in the thoracic and/or lumbar spine. SUMMARY OF BACKGROUND
      DATA: OPLL is most frequently seen in the cervical spine. The coexisting ossified
      lesions are sometimes observed in other spinal regions. However, coexisting OPLL
      in other spinal regions have not yet been precisely evaluated in patients with
      cervical OPLL. METHODS: One hundred seventy-eight patients with a diagnosis of
      cervical OPLL whose plain radiographs were obtained were included. Computed
      tomographic images of the whole spine were obtained. The ossification index (OS
      index) was newly determined according to the sum of the levels of vertebral
      bodies and intervertebral discs with OPLL. The patients were divided into 2
      groups, the group that had OPLL only in the cervical spine (C group) and the
      group that had OPLL in multilevel spinal regions other than the cervical spine (M
      group). RESULTS: Ninety-five (53.4%) had OPLL not only in the cervical spine, but
      also in other spinal regions. The M group had more females than the C group. The
      incidence of bridge formation in the cervical spine was higher in M group than in
      C group. More females had a high OS index. A positive correlation was found
      between the OS index of the cervical spine and the OS index of the thoracic and
      lumbar spine; however, the r value was small. CONCLUSION: This study demonstrated
      that more than half of the patients with cervical OPLL had coexisting OPLL in the
      thoracic and/or lumbar spine. We strongly recommend computed tomographic analysis
      of the whole spine for patients with radiographical evidence of OPLL in the
      cervical spine for the early detection of additional sites of ossification.

PMID- 23883834
TI  - Tuberculosis lymphadenitis in Ethiopia.
AB  - Tuberculosis (TB) is one of the most serious public health challenges in
      Ethiopia. Indeed, Ethiopia ranks 7th among 22 countries with a high burden of TB
      worldwide. Both pulmonary TB and extrapulmonary TB (EPTB) are issues of concern.
      Ethiopia ranks 3rd in terms of the number of EPTB patients worldwide, with TB
      lymphadenitis (TBL) being the most common. According to the World Health
      Organization's Global TB Report 2009, the estimated number of TB patients in
      Ethiopia was 314,267 in 2007, with an estimated incidence rate of 378 patients
      per 100,000 population. Furthermore, 36% patients suffered from EPTB, with TBL
      accounting for 80% of these patients. In Ethiopia, pathological services,
      culture, and drug susceptibility testing for mycobacterium species are not
      available as routine tests, not even for cases with suspected infection by drug
      resistant strains. Therefore, the management of multidrug-resistant (MDR) TB in
      Ethiopia is currently unsatisfactory. Against this background, a high index of
      clinical doubt and timely use of diagnostic methods, prompt confirmation of
      diagnosis, and early initiation of specific anti-TB treatment are the key factors
      for the successful management of MDR-TB and TBL in Ethiopia. 

PMID- 23883835
TI  - The burden of rotavirus gastroenteritis among Japanese children during its peak
      months: an internet survey.
AB  - Rotavirus gastroenteritis (RVGE) is one of the most common early childhood
      diseases; however, little information exists on the frequency of RVGE attacks
      during peak epidemic months and the subsequent clinical consequences in Japanese
      children. Therefore, we conducted a nationwide internet survey that targeted
      mothers whose children recently experienced an episode of RVGE or influenza from
      January 2011 to April 2011. Data concerning the incidence and clinical
      consequences of RVGE and influenza among 15,137 children aged <3 years were
      collected. Of these, 1,286 children who experienced an RVGE episode and 1,487
      children who experienced an influenza episode visited a physician or required
      hospital admission. Data analysis of 867 RVGE episodes and 897 influenza episodes
      found that 25% of children with RVGE required 8-14 days for recovery, 28%
      received intravenous rehydration, 7% were hospitalized, 15% visited an emergency
      department, 70% sought medical interventions >=2 times, and 32% sought medical
      intervention >=3 times. Compared with influenza, RVGE required a longer recovery
      period, and was associated with more frequent episodes of intravenous
      rehydration, hospitalization, and emergency department and physician visits. Our
      results indicate that, like influenza, RVGE occurring during peak epidemic months
      in children aged <3 years imposes a substantial burden on families and medical
      institutions in Japan. 

PMID- 23883836
TI  - Cyclosporin A inhibits the propagation of influenza virus by interfering with a
      late event in the virus life cycle.
AB  - Influenza is a global public health problem that causes a serious respiratory
      disease. Influenza virus frequently undergoes amino acid substitutions, which
      result in the emergence of drug-resistant viruses. To control influenza viruses
      that are resistant to currently available drugs, it is essential to develop new
      antiviral drugs with a novel molecular target. Here, we report that cyclosporin A
      (CsA) inhibits the propagation of influenza virus in A549 cells by interfering
      with a late event in the virus life cycle. CsA did not affect adsorption,
      internalization, viral RNA replication, or synthesis of viral proteins in A549
      cells, but inhibited the step(s) after viral protein synthesis, such as assembly
      or budding. In addition, siRNA-mediated knockdown of the expression of the major
      CsA targets, namely cyclophilin A (CypA), cyclophilin B (CypB), and P
      glycoprotein (Pgp), did not inhibit influenza virus propagation. These results
      suggest that CsA inhibits virus propagation by mechanism(s) independent of the
      inhibition of the function of CypA, CypB, and Pgp. CsA may target an unknown
      molecule that works as a positive regulator in the propagation of influenza
      virus. Our findings would contribute to the development of a novel anti-influenza
      virus therapy and clarification of the regulatory mechanism of influenza virus
      multiplication. 

PMID- 23883837
TI  - Serotyping and antimicrobial susceptibility of Salmonella spp.: nationwide
      multicenter study in Korea.
AB  - The study aimed to investigate the prevalence of various serotypes and extended
      spectrum beta-lactamase-producing features of Salmonella strains and to determine
      the antimicrobial susceptibility of 256 Salmonella strains other than Salmonella
      serotype Typhi, which were isolated at 12 university hospitals in Korea. We
      identified 46 serotypes of Salmonella spp. Serogroup D was the most common
      (39.5%), followed by B (32.4%), C (22.7%), E (2.7%), A (2.3%), and G (0.4%). The
      three most common Salmonella serotypes were Enteritidis (36.3%), Typhimurium
      (16.8%), and Infantis (7.8%). Six strains that belonged to serotype Paratyphi A
      and nine that belonged to serotype Paratyphi B were also detected. The 256
      Salmonella strains had a 38.7% rate of resistance to ampicillin, 23.0% to
      chloramphenicol, 8.2% to cefotaxime, 8.6% to ceftriaxone, and 6.3% to
      trimethoprim-sulfamethoxazole. The antimicrobial resistance rates of Salmonella
      serogroups B and D were higher than those of the other serogroups. Seven isolates
      carried blaCTX-M: four CTX-M-15, two CTX-M-14, and one CTX-M-3. 

PMID- 23883838
TI  - Epidemiological features and surveillance performance of measles in the Republic
      of Korea, 2002-2011.
AB  - Measles was declared eliminated from the Republic of Korea in 2006; however,
      recently the number of reported cases has been gradually increasing. To address
      this issue, we summarized the measles surveillance data collected during 2002
      2011, and aimed to evaluate the performance of the current surveillance system in
      Korea. We analyzed data from the national surveillance system to describe the
      occurrence of measles. Surveillance indicators proposed by the World Health
      Organization were used to evaluate the performance of the current measles
      surveillance system. Between 2002 and 2005, a gradual decrease in confirmed cases
      of measles was noted, whereas cyclical increases were noted from 2006 to 2011.
      Since 2006, confirmed cases of measles were more likely to be identified by
      laboratory methods. In general, the incidence of confirmed case was less than one
      per million in Korea; however, this figure increased in 2002 (1.3/million), 2007
      (4.0), and 2010 (2.3). Most cases were occurred in the age groups 0-23 months and
      12-17 years. Laboratory testing was performed in most suspected cases; however,
      the proportion of discarded cases was low. Overall, more than half of the
      reported cases experienced an onset of symptoms from April to June. The incidence
      of measles is relatively low in Korea, and the laboratory surveillance may have
      helped in identifying under-diagnosed cases within the country. It remains
      important to continuously assess the surveillance data to improve the
      surveillance performance. 

PMID- 23883839
TI  - Prevalence of Salmonella in wild snakes in Japan.
AB  - A total of 87 wild snakes of 6 species in 2 families collected in Japan were
      examined for the presence of Salmonella. The prevalence of Salmonella was 58.6%,
      and that of Salmonella enterica subspecies I, which includes most human
      pathogenic serotypes, accounted for 12.6%. S. enterica subspecies I was isolated
      from Japanese grass snakes and Japanese four-striped snakes, and the isolates
      belonged to 6 serotypes: S. enterica subspecies enterica serotypes Eastbourne,
      Mikawashima, Narashino, Newport, Saintpaul, and Thompson. The prevalence of S.
      enterica subspecies IIIb was higher (41.4%) than that of S. enterica subspecies
      I, and it was isolated from 4 snake species. The prevalence of Salmonella
      enterica subspecies and isolation of serotypes that are commonly detected in
      reptiles and human salmonellosis suggest that wild snakes may become a source of
      Salmonella infection. 

PMID- 23883840
TI  - Monitoring genetic diversity of influenza A(H1N1)pdm09 virus circulating during
      the post-pandemic period in Turkey.
AB  - The aimes of the present study were to monitor genetic alterations in the
      hemagglutin (HA) gene and oseltamivir resistance-related alterations in the
      neuraminidase (NA) gene of influenza A(H1N1)pdm09 viral isolates detected during
      the post-pandemic period in Turkey. A total of 2601 clinical specimens obtained
      from suspected cases of influenza A(H1N1)pdm09 viral infections were analyzed by
      real-time reverse transcription polymerase chain reaction. Viral RNA was detected
      in 233 (9%) clinical specimens. Sequence analysis of the HA gene in 16 random
      isolates showed >98.7% homology among each other and with the
      A/California/07/2009 vaccine strain. These 16 isolates had common (75%-100%)
      amino acid substitiutions at positions P83S, D97N, S203T, R205K, I216V, V249L,
      I321V, and E374K in the HA gene. In addition, two additional rare mutations were
      also observed at positions S162N (addition of a glycosylation site, 6.25%) and
      A186T (receptor binding region, 6.25%). On the basis of amino acid substitutions
      in the HA1 domain, majority of the Turkish isolates were classified in the
      genetic group v and others in the genetic groups ii, iii, and vi. In the present
      study, we observed an increase in the variety and ratio of mutations detected in
      the HA1 and HA2 domains of the HA gene; however, these alterations have not yet
      resulted in vaccine escape mutants in Turkey. In addition, analysis of the NA
      regions of the isolates revealed that oseltamivir resistance was not an issue in
      Turkey. 

PMID- 23883841
TI  - HIV-1 subtypes and primary antiretroviral resistance mutations in antiretroviral
      therapy naive HIV-1 infected individuals in Turkey.
AB  - In this study, we determined the subtype distribution and the primary drug
      resistant mutations in HIV-1 strains isolated from antiretroviral therapy (ART)
      naive patients in Turkey. The study included 117 newly diagnosed HIV-1 positive
      Turkish patients. HIV-1 subtypes and circulating recombinant forms (CRFs) were
      identified by phylogenetic analysis (neighbor-joining method), and drug-resistant
      mutations were analyzed according to the 2009 World Health Organization list of
      surveillance drug-resistant mutations. Subtype CRFs (CRF 02_AG, CRF 01_AE, CRF
      12_BF and CRF 03_AB; 47%, 55/117) and B (33.3%, 39/117) were identified as the
      most common occurring HIV-1 subtypes in Turkey. The patients had primary
      antiretroviral resistance mutations to nucleos(t)ide reverse transcriptase (RT)
      inhibitors (NRTIs) (M41L, T215C, T215D, and K219Q), non-nucleoside RT inhibitors
      (NNRTIs; K103N), and protease inhibitors (PIs; I47V, G73S). The prevalence of
      overall primary antiretroviral resistance was 7.6% (9/117) in HIV-1 patients from
      Turkey and drug-resistant rate for NRTIs, NNRTIs, and PIs were 4.2% (5/117), 1.7%
      (2/117), and 1.7% (2/117), respectively. In this study, various CRFs of HIV-1
      were determined, for the first time, in Turkey. The prevalence of HIV-1 primary
      drug-resistant mutations in ART-naive patients suggested that resistance testing
      should be incorporated as an integral part of HIV management, and the choice of a
      first-line therapy regime should be guided by the results of genotypic resistance
      in Turkey. 

PMID- 23883842
TI  - A case series of chronic necrotizing pulmonary aspergillosis and a new proposal.
AB  - Chronic necrotizing pulmonary aspergillosis (CNPA) is an indolent, cavitating
      process in the lungs resulting from invasion of lung tissue by Aspergillus spp.
      However, most previous reports have not found any clear evidence of parenchymal
      invasion, and clinical distinction between CNPA and chronic cavitary pulmonary
      aspergillosis (CCPA) is difficult. We performed a histopathological study of lung
      specimens obtained by autopsy, surgical resection, or biopsy to clarify the
      characteristic pathological and clinical features of CNPA. We present 4 cases of
      proven CNPA, diagnosed by histological demonstration of tissue invasion by the
      fungus, and present its clinical features. These 4 patients were male, and the
      mean age was 62 years (range, 51-75 years). Their underlying conditions were
      chronic obstructive pulmonary disease (n = 3), sequelae of pulmonary tuberculosis
      (n = 2), and diabetes mellitus (n = 1). Aspergillus precipitation tests were
      positive for 3; and Aspergillus antigen tests were positive for 2 on admission,
      and subsequently, for all 4. The isolated pathogens were Aspergillus niger for 1
      and A. fumigatus for 1. Initial radiographic findings were infiltrates or nodular
      lesions, which slowly progressed and cavitated before the appearance of fungus
      balls. Although CNPA has characteristic pathological features, it is clinically
      difficult to distinguish CNPA from CCPA. We propose to use the term chronic
      progressive pulmonary aspergillosis for both CNPA and CCPA. 

PMID- 23883843
TI  - Clinical experience of raltegravir with abacavir/lamivudine or
      zidovudine/lamivudine in HIV-infected Korean adults.
AB  - The efficacy and safety of raltegravir (RAL) with tenofovir (TDF)/emtricitabine
      (FTC) have been well studied in human immunodeficiency virus (HIV)-infected
      patients. However, limited clinical data are available on the use of RAL with
      abacavir (ABC)/lamivudine (3TC) or zidovudine (ZDV)/3TC. We investigated HIV-1
      infected Korean adults, including 13 antiretroviral-naive patients and 15
      antiretroviral-experienced patients, treated with RAL plus ABC/3TC or ZDV/3TC.
      Virological suppression was achieved in 12 of the 13 (92%) antiretroviral-naive
      patients within 24 weeks and in all (100%) patients within 96 weeks. In 13 of the
      15 treatment-experienced patients, ritonavir-boosted lopinavir (LPV/r) was
      replaced with RAL because of hyperlipidemia (n = 11) and diarrhea (n = 2). A
      significant decrease in median total cholesterol, low-density lipoprotein
      cholesterol, and triglyceride levels was observed in these patients (P < 0.01,
      each). No adverse event related to RAL was observed in any of the 28 patients.
      The RAL plus ABC/3TC or ZDV/3TC regimens were effective and safe in
      antiretroviral-naive Korean HIV-infected patients, and replacing LPV/r with RAL
      significantly improved lipid abnormalities in patients previously treated with
      regimens including LPV/r. 

PMID- 23883844
TI  - Optic neuritis following aseptic meningitis associated with modified measles: a
      case report.
AB  - In this study, we report the case of a 35-year-old woman with modified measles
      complicated by aseptic meningitis and subsequent optic neuritis. Although her
      initial manifestations were only flu-like symptoms without any Koplik's spots or
      skin rashes, virological testing confirmed an acute measles infection.
      Subsequently, right optic neuritis appeared after aseptic meningitis and was
      completely resolved following steroid pulse therapy. In general, modified measles
      is believed to be associated with mild symptoms and few neurological
      complications; however, our present observations demonstrated that modified
      measles can cause rapid neurological complications. 

PMID- 23883845
TI  - Outbreak of multiresistant OXA-24- and OXA-51-producing Acinetobacter baumannii
      in an internal medicine ward.
AB  - Here we describe the clinical, microbiological, epidemiological, and molecular
      characterization of an outbreak of multidrug-resistant Acinetobacter baumannii
      (MRAB) involving 5 patients admitted to the internal medicine ward of our
      hospital. Over a 6-week period, 5 MRAB isolates were recovered from 5 patients,
      including 1 with fatal meningitis, 3 with skin and soft tissue infections, and 1
      with respiratory colonization. One sample obtained during environmental
      monitoring in the ward was A. baumannii-positive. According to the pulsed-field
      gel electrophoresis typing results, the strains isolated from all patients and
      the environmental sample belonged to a single clone, identified as ST79 by
      multilocus sequence typing. The blaOXA-24 and blaOXA-51 carbapenemases were
      detected in all isolates. Four patients died, but only the death of the
      meningitis patient was probably related to the A. baumannii infection. The
      infection source was probably the hands of the healthcare workers because the
      outbreak strain was isolated from the surface of a serum container. The results
      of the present study revealed the importance of strict adherence to control
      measures by all healthcare workers because the consequences of noncompliance can
      be very serious. 

PMID- 23883846
TI  - Congenital tuberculosis because of misdiagnosed maternal pulmonary tuberculosis
      during pregnancy.
AB  - We report the death of an infant due to severe sepsis caused by congenital
      tuberculosis following treatment with antituberculous drugs and antibiotics, who
      was born to a mother with misdiagnosed symptomatic pulmonary tuberculosis during
      pregnancy. Therefore, pregnant women with chronic cough and constitutional
      symptoms must be examined for pulmonary tuberculosis, particularly in
      tuberculosis endemic areas. 

PMID- 23883847
TI  - Retrospective analysis of epidemiological aspects of Vibrio vulnificus infections
      in Korea in 2001-2010.
AB  - In this study, we performed a retrospective, quantitative analysis of the
      epidemiological aspects and risk factors of Vibrio vulnificus infections in Korea
      from 2001 to 2010. In a total of 588 V. vulnificus infection cases (prevalence
      rate, 0.12 cases/100,000 persons), 285 were fatal (case-fatality rate [CFR],
      48.5%). Males were more significantly infected by V. vulnificus than females
      (86.1% versus 13.9%; P < 0.01), and a higher incidence of V. vulnificus
      infections was observed in people aged more than 40 years (95.1%; P < 0.01).
      Moreover, most V. vulnificus infections occurred in the unemployed (42.0%; P <
      0.01). The seasonal patterns of outbreaks revealed that most outbreaks occurred
      in June (early summer) throughout November (the end of autumn) (99.6%; P < 0.01),
      and significantly more outbreaks occurred in the southern part (65.3%) of the
      Korean peninsula compared with those in the northern (29.4%) and central (5.3%)
      parts (P < 0.01). In addition, the number of V. vulnificus infections was
      significantly higher in rural and coastal villages (69.9%) than in urban areas
      (30.1%) (P < 0.01). In conclusion, because of the rapid aggravation and high CFR
      of V. vulnificus infections, public health education should strongly recommend
      avoiding raw seafood products and limited exposure to marine water during the
      summer. 

PMID- 23883848
TI  - Antimicrobial susceptibility of Streptococcus gallolyticus isolated from humans
      and animals.
AB  - Susceptibilities to some antimicrobial agents and distribution of genes
      associated with resistance were examined in a total of 66 Streptococcus
      gallolyticus isolates and reference strains from various sources. All the tested
      bacteria were susceptible to vancomycin, penicillin G, and ampicillin. Most of
      the erythromycin-resistant isolates were observed in human clinical samples.
      Tetracycline and doxycycline resistance was prevalent in the isolates from human
      patients, diseased animals, and healthy broiler chickens, while the prevalence
      was significantly lower in the isolates from healthy mammals. All the isolates
      resistant to tetracycline possessed tet(M) and/or tet(L) and/or tet(O) genes.
      However, most isolates from healthy animals, which were susceptible to
      tetracycline, possessed the above-cited resistance genes, implying the potential
      ability for resistance under exposure to the corresponding antimicrobial agents. 

PMID- 23883849
TI  - Antimicrobial resistance of human Salmonella enterica serovar Typhimurium U302
      strains: prevalence of R-type ASSuT in Slovakia, 2006-2011.
AB  - Salmonella enterica serovar Typhimurium is a common cause of non-typhoid
      salmonellosis in humans. Since 2006, an increase in the human infections caused
      by U302 phage type in Slovakia has been documented and, from 2006 to 2011, a
      total of 291 U302 human strains were isolated. Antimicrobial susceptibility
      testing demonstrated that these strains had a high overall antimicrobial
      resistance and 244 (83.8%) of the tested strains were multidrug-resistant (MDR).
      The most prevalent resistance was to ampicillin, streptomycin, sulfisoxazole, and
      tetracycline (R-type ASSuT), which was verified in 87 (29.9%) strains. The annual
      rate of this resistance type varies, but the largest number of these strains were
      identified in 2009 and 2010. The classical pentaresistance phenotype (R-type
      ACSSuT), characteristic of the DT104 phage type, was found only in 40 (13.7%)
      U302 strains. These results suggested that although the prevalence of DT104 phage
      type has decreased, ASSuT as well as ACSSuT resistance markers continue to
      circulate. Therefore, continual surveillance of the occurrence of these and
      similar MDR phage types is necessary. 

PMID- 23883850
TI  - Efficacy of various larvicides against Aedes aegypti immatures in the laboratory.
AB  - We conducted a laboratory study to evaluate the efficacy of control agents
      against small larvae, large larvae, and pupae of Aedes aegypti to determine an
      appropriate larvicide regime to employ in emergency dengue control programs. The
      control agents included Bacillus thuringiensis var. israelensis (Bti),
      pyriproxyfen (an insect growth regulator), a larvicidal oil, Aquatain AMF
      (polydimethylsiloxane, a monomolecular film), and temephos at the recommend
      application dosages and rates. Our results showed that Bti, pyriproxyfen, and
      temephos were efficacious (100% mortality) against larvae, irrespective of the
      instar stage, but not against pupae of Ae. aegypti (1.5-7.8% mortality). Aquatain
      AMF, on the other hand, was very effective at controlling the pupal stage (100%
      mortality), but had limited efficacy against small larvae (38.0% mortality) and
      large larvae (78.0% mortality). The larvicidal oil was effective against all
      immature stages (93.3-100% mortality). Therefore, we concluded that for
      effectively interrupting the dengue transmission cycle, larvicides that kill the
      pupal stage (Aquatain AMF or larvicidal oil) should be included in an emergency
      dengue control program in addition to Bti, pyriproxyfen, or temephos. 

PMID- 23883851
TI  - Renal abscess involving mucormycosis by immunohistochemical detection in a
      patient with acute lymphocytic leukemia: a case report and literature review.
AB  - A 14-year-old girl with acute lymphocytic leukemia complained of right flank pain
      and fever. As her fever was prolonged, she underwent renal biopsy and was
      diagnosed with mucormycosis. We performed right nephrectomy, and subsequent
      pathological examination of her tissue specimen also detected mucormycosis. Here,
      we report a rare case of renal mucormycotic abscess. 

PMID- 23883852
TI  - Electron microscopic study of Kudoa septempunctata infecting Paralichthys
      olivaceus (olive flounder).
AB  - Kudoa septempunctata is a myxosporean parasite of Paralichthys olivaceus (olive
      flounder) that causes more than 50 cases of foodborne illness in Japan each year.
      For quantitatively assessing the presence of K. septempunctata spores in the
      causative fish at food poisoning outbreaks, both a direct observation method
      using microscopy and a quantitative real-time PCR (qRT-PCR) method are officially
      accepted in Japan. However, lower correlations have been often noticed between
      the number of spores counted using the direct observation method and the DNA
      amount determined using the qRT-PCR method. To elucidate the cause of this
      discrepancy, we observed muscle tissues of infected olive flounders with K.
      septempunctata by transmission electron microscopy. The images demonstrated
      unsynchronized development of K. septempunctata spores in plasmodia found within
      myofibers; in other words, the plasmodium contained not only developed spores
      with completed shell valves but also developing spores (sporoblasts) composed of
      spore-forming cells without shell valves. Furthermore, the ratio between
      developed spores and sporoblasts varied at different parts of muscles. The direct
      microscopic observation method could count developed spores, whereas the qRT-PCR
      method could quantify the amount of not only spores but also sporoblastic cells
      regardless of the cellular development and differentiation. Considering that the
      food toxicity caused by K. septempunctata is induced by viable spores passing
      through the gastric environment, the direct observation method counting only
      developed spores is better than the qRT-PCR method for assessing the cause of
      foodborne illness at the outbreak as well as the risk of human illness in
      monitoring surveys of aquacultured or natural-water fish. 

PMID- 23883853
TI  - Predicting the evolution of the 2013 H7N9 epidemic in China.

PMID- 23883854
TI  - An outbreak of foodborne botulism in Surat Thani Province, Thailand, 2012.

PMID- 23883855
TI  - Investigation of a diffused outbreak in Yamaguchi Prefecture in 2012 using
      multiple molecular typing methods.

PMID- 23883858
TI  - Continuous theta burst transcranial magnetic stimulation reduces resting state
      connectivity between visual areas.
AB  - Continuous theta burst stimulation (cTBS) is a technique that allows for altering
      of brain activity. Research to date has focused on the effect of cTBS on the
      target area, but less is known about its effects on the resting state functional
      connectivity between different brain regions. We investigated this issue by
      applying cTBS to the occipital cortex and probing its influence in
      retinotopically defined regions in early visual cortex using functional MRI. We
      found that occipital cTBS reliably decreased the resting state functional
      connectivity (i.e., the correlation of spontaneous activity) between regions of
      the early visual cortex. In the context of a perceptual task, such an effect
      could mean that cTBS affects the strength of the perceptual signal, its
      variability, or both. We investigated this issue in a second experiment in which
      subjects performed a perceptual discrimination task and indicated their level of
      certainty on each trial. The results showed that occipital cTBS decreased both
      subjects' accuracy and confidence. Signal detection modeling suggested that these
      impairments resulted primarily from a decreased strength of the perceptual
      signal, with a nonsignificant trend of a decrease in signal variability. We
      discuss the implications of these experiments for understanding the mechanisms by
      which cTBS influences brain activity and perceptual processes. 

PMID- 23883857
TI  - Neuropeptide S: a novel regulator of pain-related amygdala plasticity and
      behaviors.
AB  - Amygdala plasticity is an important contributor to the emotional-affective
      dimension of pain. Recently discovered neuropeptide S (NPS) has anxiolytic
      properties through actions in the amygdala. Behavioral data also suggest
      antinociceptive effects of centrally acting NPS, but site and mechanism of action
      remain to be determined. This is the first electrophysiological analysis of pain
      related NPS effects in the brain. We combined whole cell patch-clamp recordings
      in brain slices and behavioral assays to test the hypothesis that NPS activates
      synaptic inhibition of amygdala output to suppress pain behavior in an arthritis
      pain model. Recordings of neurons in the laterocapsular division of the central
      nucleus (CeLC), which serves pain-related amygdala output functions, show that
      NPS inhibited the enhanced excitatory drive [monosynaptic excitatory postsynaptic
      currents (EPSCs)] from the basolateral amygdala (BLA) in the pain state. As shown
      by miniature EPSC analysis, the inhibitory effect of NPS did not involve direct
      postsynaptic action on CeLC neurons but rather a presynaptic, action potential
      dependent network mechanism. Indeed, NPS increased external capsule (EC)-driven
      synaptic inhibition of CeLC neurons through PKA-dependent facilitatory
      postsynaptic action on a cluster of inhibitory intercalated (ITC) cells. NPS had
      no effect on BLA neurons. High-frequency stimulation (HFS) of excitatory EC
      inputs to ITC cells also inhibited synaptic activation of CeLC neurons, providing
      further evidence that ITC activation can control amygdala output. The cellular
      mechanisms by which EC-driven synaptic inhibition controls CeLC output remain to
      be determined. Administration of NPS into ITC, but not CeLC, also inhibited
      vocalizations and anxiety-like behavior in arthritic rats. A selective NPS
      receptor antagonist ([d-Cys(tBu)(5)]NPS) blocked electrophysiological and
      behavioral effects of NPS. Thus NPS is a novel tool to control amygdala output
      and pain-related affective behaviors through a direct action on inhibitory ITC
      cells.

PMID- 23883859
TI  - Participation of a persistent sodium current and calcium-activated nonspecific
      cationic current to burst generation in trigeminal principal sensory neurons.
AB  - The properties of neurons participating in masticatory rhythmogenesis are not
      clearly understood. Neurons within the dorsal trigeminal principal sensory
      nucleus (dPrV) are potential candidates as components of the masticatory central
      pattern generator (CPG). The present study examines in detail the ionic
      mechanisms controlling burst generation in dPrV neurons in rat (postnatal day 8
      12) brain stem slices using whole cell and perforated patch-clamp methods.
      Nominal extracellular Ca(2+) concentration transformed tonic discharge in
      response to a maintained step pulse of current into rhythmical bursting in 38% of
      nonbursting neurons. This change in discharge mode was suppressed by riluzole, a
      persistent Na(+) current (INaP) antagonist. Veratridine, which suppresses the
      Na(+) channel inactivation mechanism, induced rhythmical bursting in nonbursting
      neurons in normal artificial cerebrospinal fluid, suggesting that INaP
      contributes to burst generation. Nominal extracellular Ca(2+) exposed a prominent
      afterdepolarizing potential (ADP) following a single spike induced by a 3-ms
      current pulse, which was suppressed, but not completely blocked, by riluzole.
      Application of BAPTA, a Ca(2+) chelator, intracellularly, or flufenamic acid, a
      Ca(2+)-activated nonspecific cationic channel (ICAN) antagonist, extracellularly
      to the bath, suppressed rhythmical bursting and the postspike ADP. Application of
      drugs to alter Ca(2+) release from endoplasmic reticulum also suppressed
      bursting. Finally, voltage-clamp methods demonstrated that nominal Ca(2+)
      facilitated INaP and induced ICAN. These data demonstrate for the first time that
      the previously observed induction in dPrV neurons of rhythmical bursting in
      nominal Ca(2+) is mediated by enhancement of INaP and onset of ICAN, which are
      dependent on intracellular Ca(2+). 

PMID- 23883860
TI  - The spread of attention across features of a surface.
AB  - Contrasting theories of visual attention have emphasized selection by spatial
      location, individual features, and whole objects. We used functional magnetic
      resonance imaging to ask whether and how attention to one feature of an object
      spreads to other features of the same object. Subjects viewed two spatially
      superimposed surfaces of random dots that were segregated by distinct color
      motion conjunctions. The color and direction of motion of each surface changed
      smoothly and in a cyclical fashion. Subjects were required to track one feature
      (e.g., color) of one of the two surfaces and detect brief moments when the
      attended feature diverged from its smooth trajectory. To tease apart the effect
      of attention to individual features on the hemodynamic response, we used a
      frequency-tagging scheme. In this scheme, the stimulus features (color and
      direction of motion) are modulated periodically at distinct frequencies so that
      the contribution of each feature to the hemodynamics can be inferred from the
      harmonic response at the corresponding frequency. We found that attention to one
      feature (e.g., color) of one surface increased the response modulation not only
      to the attended feature but also to the other feature (e.g., motion) of the same
      surface. This attentional modulation was evident in multiple visual areas and was
      present as early as V1. The spread of attention to the behaviorally irrelevant
      features of a surface suggests that attention may automatically select all
      features of a single object. Thus object-based attention may be supported by an
      enhancement of feature-specific sensory signals in the visual cortex. 

PMID- 23883861
TI  - Perception-action dissociations depend on the luminance contrast of the stimuli.
AB  - The observation that near-threshold low-contrast visual distractors can equally
      influence perceptual state and goal-directed motor responses was recently taken
      as an argument against a sharp separation between a conscious vision for
      perception and an unconscious vision for action. However, data supporting the
      dual visual system theory have principally involved high-contrast stimuli. In the
      present study, we assessed the effect of varying the contrast of a near-threshold
      visual distractor while keeping its visibility constant with backward noise
      masks. Eight participants performed fast manual reaching movements toward a
      highly visible target while subsequently reporting the presence/absence of a near
      threshold distractor appearing at the opposite location with respect to the body
      midline. For all distractor contrasts, hand trajectory deviations toward the
      distractor were observed when the distractor was present and detected. When the
      distractor remained undetected deviations also occurred, but for higher
      contrasts. The subliminal motor effect traditionally observed in visual masking
      studies may therefore primarily depend on the luminance contrast of the
      interfering stimuli. These results suggest that dissociations between perceptual
      and motor responses can be explained by a single-signal model involving
      differential thresholds for perception and action that are specifically modulated
      as a function of both the requirements of the task and the contrast level of the
      stimuli. Such modulation is compatible with neurophysiological accounts of visual
      masking in which feedforward activation to--and feedback activation from--higher
      visual areas are correlated with the actual presence of the stimulation and its
      conscious perception, respectively.

PMID- 23883862
TI  - Muscimol inactivation of caudal fastigial nucleus and posterior interposed
      nucleus in monkeys with strabismus.
AB  - Previously, we showed that neurons in the supraoculomotor area (SOA), known to
      encode vergence angle in normal monkeys, encode the horizontal eye misalignment
      in strabismic monkeys. The SOA receives afferent projections from the caudal
      fastigial nucleus (cFN) and the posterior interposed nucleus (PIN) in the
      cerebellum. The objectives of the present study were to investigate the potential
      roles of the cFN and PIN in 1) conjugate eye movements and 2) binocular eye
      alignment in strabismic monkeys. We used unilateral injections of the GABAA
      agonist muscimol to reversibly inactivate the cFN (4 injections in exotropic
      monkey S1 with ~ 4 degrees  of exotropia; 5 injections in esotropic monkey S2
      with ~ 34 degrees  of esotropia) and the PIN (3 injections in monkey S1). cFN
      inactivation induced horizontal saccade dysmetria in all experiments (mean 39%
      increase in ipsilesional saccade gain and 26% decrease in contralesional gain).
      Also, mean contralesional smooth-pursuit gain was decreased by 31%. cFN
      inactivation induced a divergent change in eye alignment in both monkeys, with
      exotropia increasing by an average of 9.8 degrees  in monkey S1 and esotropia
      decreasing by an average of 11.2 degrees  in monkey S2 (P < 0.001). Unilateral
      PIN inactivation in monkey S1 resulted in a mean increase in the gain of upward
      saccades by 13% and also induced a convergent change in eye alignment, reducing
      exotropia by an average of 2.7 degrees  (P < 0.001). We conclude that cFN/PIN
      influences on conjugate eye movements in strabismic monkeys are similar to those
      postulated in normal monkeys and cFN/PIN play important and complementary roles
      in maintaining the steady-state misalignment in strabismus.

PMID- 23883863
TI  - N-acetylcysteine amide augments the therapeutic effect of neural stem cell-based
      antiglioma oncolytic virotherapy.
AB  - Current research has evaluated the intrinsic tumor-tropic properties of stem cell
      carriers for targeted anticancer therapy. Our laboratory has been extensively
      studying in the preclinical setting, the role of neural stem cells (NSCs) as
      delivery vehicles of CRAd-S-pk7, a gliomatropic oncolytic adenovirus (OV).
      However, the mediated toxicity of therapeutic payloads, such as oncolytic
      adenoviruses, toward cell carriers has significantly limited this targeted
      delivery approach. Following this rationale, in this study, we assessed the role
      of a novel antioxidant thiol, N-acetylcysteine amide (NACA), to prevent OV
      mediated toxicity toward NSC carriers in an orthotropic glioma xenograft mouse
      model. Our results show that the combination of NACA and CRAd-S-pk7 not only
      increases the viability of these cell carriers by preventing reactive oxygen
      species (ROS)-induced apoptosis of NSCs, but also improves the production of
      viral progeny in HB1.F3.CD NSCs. In an intracranial xenograft mouse model, the
      combination treatment of NACA and NSCs loaded with CRAd-S-pk7 showed enhanced
      CRAd-S-pk7 production and distribution in malignant tissues, which improves the
      therapeutic efficacy of NSC-based targeted antiglioma oncolytic virotherapy.
      These data demonstrate that the combination of NACA and NSCs loaded with CRAd-S
      pk7 may be a desirable strategy to improve the therapeutic efficacy of antiglioma
      oncolytic virotherapy.

PMID- 23883865
TI  - Reader beware!

PMID- 23883864
TI  - Inactivation of hepatitis B virus replication in cultured cells and in vivo with
      engineered transcription activator-like effector nucleases.
AB  - Chronic hepatitis B virus (HBV) infection remains an important global health
      problem. Stability of the episomal covalently closed circular HBV DNA (cccDNA) is
      largely responsible for the modest curative efficacy of available therapy. Since
      licensed anti-HBV drugs have a post-transcriptional mechanism of action,
      disabling cccDNA is potentially of therapeutic benefit. To develop this approach,
      we engineered mutagenic transcription activator-like effector nucleases (TALENs)
      that target four HBV-specific sites within the viral genome. TALENs with cognate
      sequences in the S or C open-reading frames (ORFs) efficiently disrupted
      sequences at the intended sites and suppressed markers of viral replication.
      Following triple transfection of cultured HepG2.2.15 cells under mildly
      hypothermic conditions, the S TALEN caused targeted mutation in ~35% of cccDNA
      molecules. Markers of viral replication were also inhibited in vivo in a murine
      hydrodynamic injection model of HBV replication. HBV target sites within S and C
      ORFs of the injected HBV DNA were mutated without evidence of toxicity. These
      findings are the first to demonstrate a targeted nuclease-mediated disruption of
      HBV cccDNA. Efficacy in vivo also indicates that these engineered nucleases have
      potential for use in treatment of chronic HBV infection.

PMID- 23883866
TI  - A case of fatal iliac vein rupture associated with May-Thurner syndrome.
AB  - May-Thurner syndrome results from long-standing compression of the left common
      iliac vein (LCIV) and is characterized by the formation of intraluminal spurs
      leading to obstruction of blood flow and deep vein thrombosis (DVT). Increased
      intraluminal pressures may occur as a consequence of venous obstruction, which
      when coupled with other factors thought to further weaken venous wall integrity
      (ie, inflammation or hormonal imbalances) may produce spontaneous (nontraumatic)
      and potential lethal venous rupture.We report a case of DVT in a woman with
      previously undiagnosed May-Thurner syndrome and heterozygosity for factor V
      Leiden mutation on exogenous hormone therapy, with subsequent spontaneous rupture
      of the LCIV leading to fatal hemoperitoneum. Autopsy revealed fibrous
      obliteration of the junction between the LCIV and inferior vena cava with
      associated DVT, transmural venous rupture, and thrombophlebitis. 

PMID- 23883867
TI  - Incidentalomas revealed by abdominopelvic computed tomography scans performed in
      body packers.
AB  - BACKGROUND: Body packing is the transport of internally concealed narcotic
      substances. These may take the form of pellets or sachets, ingested or inserted
      per anus or per vagina. In France, abdominopelvic scanning without contrast
      medium injection is used to check the complete evacuation of ingested narcotics.
      This sometimes leads to the discovery of incident pathologies, also known as
      "incidentalomas." OBJECTIVE: Our study described incidentaloma detected by
      abdominopelvic computed tomography (CT) scanning in body packers. This
      monocentric prospective study concerned 100 CT scan images from body packers
      managed in our secure medical unit between September 2009 and April 2010.
      RESULTS: Thirty-one incidentalomas were discovered on 18 abdominopelvic CT scans,
      including 2 women. Ten CT scan examinations revealed 1 suspect image, 5 scans
      included 5 suspect images, 2 scans included 3 suspect images, and 1 scan included
      5 suspects images. Once the complete evacuation of all foreign bodies is
      confirmed, and in the absence of any surgical or medical emergency, incidentaloma
      management is entrusted to the prison doctors.

PMID- 23883868
TI  - Evaluation of forensic deaths during the month of Ramadan in Konya, Turkey,
      between 2000 and 2009.
AB  - Ramadan is a holy month for Muslim people and includes long fasting periods.
      During Ramadan, practicing Muslims not only fast, but they also abstain from any
      kind of medication, smoking, sexual intercourse, and alcohol from sunrise to
      sunset. In the 10-year period between 2000 and 2009, it was determined that a
      total of 4881 death examinations and autopsies were performed at the Konya Branch
      of the Forensic Medicine Council (Turkey). All of the reports were
      retrospectively evaluated for demographic features of the cases and the manner of
      death. In the studied time period, a total of 491 deaths (10.1%) occurred in
      Ramadan. The manner of death was accident in 369 (75.2%) of the cases in Ramadan,
      3107 (70.8%) of the other cases; suicide in 27 (5.5%) of the cases in Ramadan,
      367 (8.4%) of the other cases; and homicide in 28 (5.7%) of the cases in Ramadan,
      375 (8.5%) of the other cases. There was a significant statistical difference in
      terms of the manner of death between the deaths in Ramadan and in the remaining
      part of the year (P < 0.05). Our study suggested that there was an increase in
      accidental and natural deaths and a decrease in suicide and homicides in Ramadan.

PMID- 23883870
TI  - Statin use and fracture risk: can we quantify the healthy-user effect?
AB  - BACKGROUND: Numerous observational studies show that statin use is associated
      with lower risk of osteoporotic fractures. However, a causal relationship is not
      supported by data from randomized trials. Unmeasured confounding is implicated as
      a likely culprit for the controversy because of failure to measure and adjust for
      patient-level tendencies to engage in healthy behaviors. However, an alternative
      explanation is selection bias because of the inclusion of prevalent users of
      statins in the analysis. The relative importance of either bias has not been
      investigated in a quantitative sensitivity analysis. METHODS: We conducted a
      systematic review to summarize the pattern of association between statin use and
      fracture risk in observational studies. Our objective was to quantify the
      magnitude of unmeasured confounding and selection bias in a sensitivity analysis.
      RESULTS: In 17 published studies, the pooled relative risk for the association
      between current use of statins and fracture risk was 0.75 (95% confidence
      interval = 0.66-0.85). Upon adjustment for individual-level use of preventative
      health services, the pooled relative risk shifted by less than 5% on the log
      scale. However, a sensitivity analysis for selection bias revealed that moderate
      levels of bias could eliminate the association between statins and fracture risk.
      CONCLUSIONS: It appears that confounding from unmeasured variables cannot explain
      the protective association between statins and fractures that has been observed
      in the literature.

PMID- 23883871
TI  - A possible solution for charge sensing in vertical double quantum dots.
AB  - We report the observation of a peculiar charge stability diagram of a vertical
      double quantum dot, where the conventional Coulomb diamond edges have a sawtooth
      like shape. This feature could be understood if we assume the formation of a
      third quantum dot in the semiconductor volume which is supposed to be a part of
      the source in the standard quantum dot measurement circuit. The size of this
      additional dot is larger compared to the size of the original ones, thus the
      charging energy is smaller, but it still exceeds the thermal energy and affects
      the electron transport through the structure. Since the big dot is coupled to
      small ones, the observed effect could be utilized for charge detection, which has
      always been a problem in the case of vertical quantum dots. 

PMID- 23883869
TI  - Neoadjuvant paradigm for accelerated drug development: an ideal model in bladder
      cancer.
AB  - Neoadjuvant cisplatin-based combination chemotherapy for muscle-invasive bladder
      cancer (MIBC) has been shown to confer a survival advantage in two randomized
      clinical trials and a meta-analysis. Despite level 1 evidence supporting its
      benefit, utilization remains dismal with nearly one-half of patients ineligible
      for cisplatin-based therapy because of renal dysfunction, impaired performance
      status, and/or coexisting medical problems. This situation highlights the need
      for the development of novel therapies for the management of MIBC, a disease with
      a lethal phenotype. The neoadjuvant paradigm in bladder cancer offers many
      advantages for accelerated drug development. First, there is a greater likelihood
      of successful therapy at an earlier disease state that may be characterized by
      less genomic instability compared with the metastatic setting, with an early
      readout of activity with results determined in months rather than years. Second,
      pre- and post-treatment tumor tissue collection in patients with MIBC is
      performed as the standard of care without the need for research-directed
      biopsies, allowing for the ability to perform important correlative studies and
      to monitor tumor response to therapy in "real time." Third, pathological complete
      response (pT0) predicts for improved outcome in patients with MIBC. Fourth, there
      is a strong biological rationale with rapidly accumulating evidence for
      actionable targets in bladder cancer. This review focuses on the neoadjuvant
      paradigm for accelerated drug development using bladder cancer as the ideal
      model. 

PMID- 23883872
TI  - Serum and urine pharmacokinetics of tigecycline in obese class III and normal
      weight adults.
AB  - OBJECTIVES: To compare the serum and urine pharmacokinetics (PK) of intravenous
      tigecycline in obese class III (obese-C3) adults with those in normal weight (NW)
      adults. PATIENTS AND METHODS: Obese-C3 (n = 8) and NW (n = 4) healthy adult
      volunteers received a single intravenous dose of 100 mg of tigecycline for 30
      min. Serum (0-96 h) and urine (0-48 h) tigecycline concentrations were assayed by
      liquid chromatography with tandem mass spectrometry. Parametric population PK
      systems analyses were used to model the data and assess the effects of total body
      weight (TBW) on PK parameters. The area under the concentration-time curve
      extrapolated to infinity (AUC0-infinity) was simulated to estimate the
      probability of AUC0-infinity : MIC target attainment and cumulative fraction of
      response (CFR) based on wild-type MIC distributions of select pathogens.
      Clinicaltrials.gov: NCT01560143. RESULTS: The median (range) age, TBW and initial
      body mass index were 42 (20-50) years, 121 (61-160) kg and 43.8 (20.8-53.8)
      kg/m(2), respectively. The serum concentration-time profiles and exposures were
      similar in the obese-C3 and NW adults, with a mean urine recovery of 15.8% and
      13.4%, respectively. The median (range) AUC0-infinity was 8.19 (6.12, 11.2) and
      7.50 (6.78, 9.13) mg . h/L in the obese-C3 and NW groups, respectively. The
      clearance of tigecycline was not related to TBW. The CFR was calculated to be
      <90% against Acinetobacter baumannii, Enterobacter cloacae and Klebsiella
      pneumoniae for an AUC0-infinity : MIC target >= 6.96. CONCLUSIONS: The serum and
      urine PK of tigecycline is similar in obese-C3 and NW healthy adults. A lower CFR
      is predicted against certain Gram-negative pathogens with the current standard
      tigecycline dosing regimen, irrespective of TBW.

PMID- 23883873
TI  - Myocardial stretch in early systole is a key determinant of the synchrony of left
      ventricular mechanical activity in vivo.
AB  - BACKGROUND: Recent in-vitro observations suggest that left ventricular (LV)
      contraction is powered by 'stretch activation', an intrinsic mechanism by which
      the stretching of an activated cardiomyocyte causes delayed force redevelopment.
      We hypothesized that mechanical dyssynchrony is related to prolonged early
      systolic stretch that delays the timing of peak segmental shortening. METHODS AND
      RESULTS: The time intervals from R wave to segmental longitudinal stretch in
      early systole (Tstretch) and peak shortening (Tpeak) and the respective standard
      deviations (sigmaTstretch and sigmaTpeak) were measured by speckle-tracking
      echocardiography in 57 patients undergoing cardiac resynchronization therapy
      (CRT). The percentage of time spent in shortening, normalized to Tpeak duration
      [corrected DeltaT=(Tpeak-Tstretch)/Tpeak] correlated with LV reverse remodeling
      (reduction in end-systolic volume >= 15%). Of the 57 patients, 40 (70.2%)
      demonstrated LV reverse remodeling at an average follow-up of 263 +/- 125 days
      after CRT. At baseline, Tstretch and sigmaTstretch correlated with Tpeak and
      sigmaTpeak, respectively. Though there was no difference in Tstretch, Tpeak,
      sigmaTstretch and sigmaTpeak between responders and non-responders, corrected
      DeltaT in the mid-lateral and mid-septal segments was shorter in the responders
      (P<0.05 for both) and the average of the 2 independently predicted LV reverse
      remodeling (area under the curve: 0.77, P=0.001). CONCLUSIONS: Mapping LV
      segmental shortening in relation to early systolic stretch may aid dyssynchrony
      assessment in patients undergoing CRT. 

PMID- 23883875
TI  - Omega-3 polyunsaturated fatty acids and coronary unstable plaque. Hint to further
      reduce coronary events.

PMID- 23883874
TI  - Rho-kinase activation in patients with heart failure.
AB  - BACKGROUND: Heart failure (HF) is a complex clinical syndrome, resulting from
      structural and/or functional cardiac disease. The aim of this study was to
      determine whether the activity of Rho-kinase, which has been identified as an
      important therapeutic target of cardiovascular disease, is enhanced in HF
      patients. METHODS AND RESULTS: Total and phosphorylated forms of myosin binding
      subunit (t-MBS and p-MBS), a substrate of Rho-kinase, were measured on western
      blotting in circulating leukocytes, and the p-MBS/t-MBS ratio was defined as an
      index of systemic Rho-kinase activity. First, during the time-course of acute HF
      (n=12), Rho-kinase activity was significantly elevated in the acute phase
      compared to the chronic phase (1.19 +/- 0.06 vs. 0.97 +/- 0.04, P<0.05). Next,
      Rho-kinase activity was examined in 30 controls and 130 chronic HF patients
      (cardiomyopathy, n=57; valvular heart disease, n=35; ischemic heart disease
      [IHD], n=33; and others, n=5). As compared with the controls, Rho-kinase activity
      was significantly elevated in the total HF group (1.14 +/- 0.02 vs. 0.77 +/-
      0.05, P<0.0001) and in each underlying heart disease (P<0.05 each). Importantly,
      in the high-risk non-IHD group, Rho-kinase activity was significantly associated
      with plasma brain nutriuretic peptide level. Finally, p-MBS was expressed in
      myocardial biopsy samples (immunohistochemistry) in chronic HF patients (n=36),
      independent of Rho-kinase activity in leukocytes. CONCLUSIONS: Rho-kinase is
      activated in HF patients, suggesting that it could be a new therapeutic target of
      the disorder.  

PMID- 23883876
TI  - Linoleic acid attenuates endothelium-derived relaxing factor production by
      suppressing cAMP-hydrolyzing phosphodiesterase activity.
AB  - BACKGROUND: Linoleic acid (LA) promotes monocyte chemotaxis and cell adhesion
      molecules such as MCP-1 and VCAM-1, which contribute to atherosclerogenesis.
      These molecules are restrained by endothelium-derived relaxing factors (EDRFs),
      such as nitric oxide (NO) and prostaglandin I2 (PGI2). Hence, the expressions of
      MCP-1 and VCAM-1 upregulated by LA may be partly attributable to decreased EDRF
      production. However, effect of LA on EDRF production remains controversial.
      METHODS AND RESULTS: The present study aimed to examine the effects of LA and
      other free fatty acids on EDRF production and the endothelial Ca(2+) responses
      that mediate EDRF production, using primary cultured porcine aortic endothelial
      cells (PAECs). LA at 0.1-5 MUmol/L attenuated bradykinin (BK)-induced NO and PGI2
      production while suppressing the BK-induced Ca(2+) response dose-dependently. The
      inhibitory effect of LA on the Ca(2+) response was eliminated by adenylate
      cyclase inhibitor SQ22536, boosted by cAMP-hydrolyzing phosphodiesterase (PDE)
      inhibitor, rolipram, and mimicked by plasma membrane permeable 8-bromo-cAMP.
      Moreover, LA was confirmed to dose-dependently increase intracellular cAMP levels
      and selectively inhibit cAMP-hydrolyzing PDE activity in vitro. In contrast, none
      of palmitic, stearic, or oleic acid affected BK-induced EDRF production or Ca(2+)
      responses, or induced intracellular cAMP accumulation. CONCLUSIONS: LA induced
      intracellular cAMP accumulation by inhibiting cAMP-hydrolyzing PDE activity, thus
      resulting in attenuation of Ca(2+) responses and EDRF production in PAECs.

PMID- 23883877
TI  - Clinical significance of abnormal relaxation pattern of the transmitral flow
      velocity waveform in older patients with preserved left ventricular ejection
      fraction.
AB  - BACKGROUND: The pathophysiology of abnormal relaxation pattern in the transmitral
      flow (TMF) velocity waveform has not been fully elucidated. METHODS AND RESULTS:
      A total of 173 patients who underwent comprehensive Doppler echocardiography and
      diagnostic cardiac catheterization for coronary artery disease were enrolled in
      the study. Peak early and late diastolic TMF velocities (E and A, respectively)
      were measured. Minimum left ventricular (LV) pressure; LV pre-A wave pressure
      (surrogate of mean left atrial [LA] pressure); time constant (tau) of LV pressure
      decay; and LV ejection fraction (LVEF) were calculated. Patients with E/A ratio
      <1.0 and LVEF >= 50% were enrolled. Patients with tau >= 48 ms and those with tau
      <48 ms were compared. The 2 groups had no significant differences in E or E/A.
      Minimum LV pressure (6.9 +/- 2.2 mmHg vs. 3.6 +/- 2.9 mmHg, P<0.0001) and LV pre
      A wave pressure (9.5 +/- 2.4 mmHg vs. 6.1 +/- 3.0 mmHg, P<0.0001) were
      significantly higher in patients with tau >= 48 ms compared to those with tau <48
      ms, but the difference between the LV pre-A and minimum LV pressures was similar
      between the groups (2.6 +/- 1.4 mmHg vs. 2.5 +/- 1.5 mmHg, P=0.89). CONCLUSIONS:
      Proportional elevations in minimum LV and pre-A pressures, due to deteriorated LV
      relaxation, resulted in no changes in the pressure gradient between the LA and LV
      in early diastole, E, or E/A.  

PMID- 23883878
TI  - Asthma and atopic dermatitis are associated with increased risk of clinical
      Plasmodium falciparum malaria.
AB  - OBJECTIVES: To assess the impact of atopy and allergy on the risk of clinical
      malaria. DESIGN: A clinical and immunological allergy cross-sectional survey in a
      birth cohort of 175 children from 1 month to 14 years of age followed for up to
      15 years in a longitudinal open cohort study of malaria in Senegal. Malaria
      incidence data were available for 143 of these children (aged 4 months to 14
      years of age) for up to 15 years. Mixed-model regression analysis was used to
      determine the impact of allergy status on malaria incidence, adjusting for age,
      gender, sickle-cell trait and force of infection. MAIN OUTCOME MEASURES: Asthma,
      allergic rhinoconjunctivitis and atopic dermatitis status, the number of clinical
      Plasmodium falciparum malaria episodes since birth and associated parasite
      density. RESULTS: 12% of the children were classified as asthmatic and 10% as
      having atopic dermatitis. These groups had respectively a twofold (OR 2.12 95%;
      CI 1.46 to 3.08; p=8*10(-5)) and threefold (OR 3.15; 1.56 to 6.33; p=1.3*10(-3))
      increase in the risk of clinical P falciparum malaria once older than the age of
      peak incidence of clinical malaria (3-4 years of age). They also presented with
      higher P falciparum parasite densities (asthma: mean 105.3 parasites/MUL+/-SE
      41.0 vs 51.3+/-9.7; p=6.2*10(-3). Atopic dermatitis: 135.4+/-70.7 vs 52.3+/-11.0;
      p=0.014). There was no effect of allergy on the number of non-malaria clinical
      presentations. Individuals with allergic rhinoconjunctivitis did not have an
      increased risk of clinical malaria nor any difference in parasite densities.
      CONCLUSIONS: These results demonstrate that asthma and atopic dermatitis delay
      the development of clinical immunity to P falciparum. Despite the encouraging
      decrease in malaria incidence rates in Africa, a significant concern is the
      extent to which the increase in allergy will exacerbate the burden of malaria.
      Given the demonstrated antiparasitic effect of antihistamines, administration to
      atopic children will likely reduce the burden of clinical malaria in these
      children, increase the efficacy of first-line treatment antimalarials and
      alleviate the non-infectious consequences of atopy.

PMID- 23883879
TI  - Factors mediating HIV risk among female sex workers in Europe: a systematic
      review and ecological analysis.
AB  - OBJECTIVES: We reviewed the epidemiology of HIV and selected sexually transmitted
      infections (STIs) among female sex workers (FSWs) in WHO-defined Europe. There
      were three objectives: (1) to assess the prevalence of HIV and STIs (chlamydia,
      syphilis and gonorrhoea); (2) to describe structural and individual-level risk
      factors associated with prevalence and (3) to examine the relationship between
      structural-level factors and national estimates of HIV prevalence among FSWs.
      DESIGN: A systematic search of published and unpublished literature measuring
      HIV/STIs and risk factors among FSWs, identified through electronic databases
      published since 2005. 'Best' estimates of HIV prevalence were calculated from the
      systematic review to provide national level estimates of HIV. Associations
      between HIV prevalence and selected structural-level indicators were assessed
      using linear regression models. STUDIES REVIEWED: Of the 1993 papers identified
      in the search, 73 peer-reviewed and grey literature documents were identified as
      meeting our criteria of which 63 papers provided unique estimates of HIV and STI
      prevalence and nine reported multivariate risk factors for HIV/STI among FSWs.
      RESULTS: HIV in Europe remains low among FSWs who do not inject drugs (<1%), but
      STIs are high, particularly syphilis in the East and gonorrhoea. FSWs experience
      high levels of violence and structural risk factors associated with HIV,
      including lack of access to services and working on the street. Linear regression
      models showed HIV among FSWs to link with injecting drug use and imprisonment.
      CONCLUSIONS: Findings show that HIV prevention interventions should be nested
      inside strategies that address the social welfare of sex workers, highlighting in
      turn the need to target the social determinants of health and inequality,
      including regarding access to services, experience of violence and migration.
      Future epidemiological and intervention studies of HIV among vulnerable
      populations need to better systematically delineate how microenvironmental and
      macroenvironmental factors combine to increase or reduce HIV/STI risk.

PMID- 23883880
TI  - Gynaecological cancer follow-up: national survey of current practice in the UK.
AB  - OBJECTIVE: To establish a baseline of national practice for follow-up after
      treatment for gynaecological cancer. DESIGN: Questionnaire survey. SETTING:
      Gynaecological cancer centres and units. GEOGRAPHICAL LOCATION UK PARTICIPANTS:
      Members of the British Gynaecological Cancer Society and the National Forum of
      Gynaecological Oncology Nurses. INTERVENTIONS: A questionnaire survey. OUTCOME
      MEASURES: To determine schedules of follow-up, who provides it and what routine
      testing is used for patients who have had previous gynaecological cancer.
      RESULTS: A total of 117 responses were obtained; 115 (98%) reported hospital
      scheduled regular follow-up appointments. Two involved general practitioners.
      Follow-up was augmented or replaced by telephone follow-up in 29 responses (25%)
      and patient-initiated appointments in 38 responses (32%). A total of 80 (68%)
      cancer specialists also offered combined follow-up clinics with other
      specialties. Clinical examinations for hospital-based follow-up were mainly
      performed by doctors (67% for scheduled regular appointments and 63% for patient
      initiated appointments) while telephone follow-up was provided in the majority by
      nurses (76%). Most respondents (76/117 (65%)) provided routine tests, of which
      66/76 (87%) reported carrying out surveillance tests for ovarian cancer, 35/76
      (46%) for cervical cancer, 8/76 (11%) for vulval cancer and 7/76 (9%) for
      endometrial cancer. Patients were usually discharged after 5 years (82/117
      (70%)), whereas three (3%) were discharged after 4 years, nine (8%) after three
      years and one (1%) after 2 years. CONCLUSIONS: Practice varied but most used a
      standard hospital-based protocol of appointments for 5 years and routine tests
      were performed usually for women with ovarian cancer. A minority utilised nurse
      led or telephone follow-up. General practitioners were rarely involved in routine
      care. A randomised study comparing various models of follow-up could be
      considered.

PMID- 23883881
TI  - Comprehensive abortion care: evidence of improvements in hospital-level
      indicators in Tigray, Ethiopia.
AB  - OBJECTIVE: Approximately 18% of maternal deaths in East Africa is attributable to
      unsafe abortion. Availability of comprehensive abortion care (CAC) services at
      all levels of the healthcare system, including medical abortion, has the
      potential to increase access to safe abortion thereby reducing the burden of
      unsafe abortion. This study sought to assess trends in abortion-related morbidity
      indicators in referral hospitals. DESIGN: Researchers conducted a secondary data
      analysis on retrospectively collected data. METHODS: Data analysed were collected
      from four hospitals in the Tigray region of Ethiopia that took part in a CAC
      pilot project. Providers were trained in mid-2009 to provide abortion services
      using all available technologies. Data records from hospitals were collected in
      2012 for the years 2006 through 2012; 2006/2007 data were too sparse to include
      in the analyses. RESULTS: Trends in abortion-related services show a significant
      decrease in treatment of incomplete abortion, inverting the relationship between
      safe terminations and treatment of incompletes as a percentage of total
      abortions. Medication abortion was nearly non-existent in 2008, but increased
      steadily, representing 80% of total procedures in 2012. The inclusion of
      medication abortion and availability of CAC also contributed to a decline in
      inpatient procedures and prevalence of complications. CONCLUSIONS: The trends
      observed in the data demonstrate how increased availability of CAC services at
      all levels of the healthcare system, among other factors, can contribute to
      reductions in the burden of unsafe abortion at referral hospitals.

PMID- 23883882
TI  - Substandard and falsified medicines in the UK: a retrospective review of drug
      alerts (2001-2011).
AB  - OBJECTIVE: To determine the extent of substandard and falsified medicines in the
      UK. DESIGN: A retrospective review of drug alerts and company-led recalls.
      SETTING: The Medicines and Healthcare Products Regulatory Agency (MHRA) website
      search for drug alerts issued between 2001 and 2011. ELIGIBILITY CRITERIA: Drug
      alerts related to quality defect in medicinal products. MAIN OUTCOME MEASURE:
      Relevant data about defective medicines reported in drug alerts and company-led
      recalls, including description of the defect, type of formulation, year of the
      alert and category of the alert. RESULTS: There were 280 substandard medicines of
      which 222 were recalled. The two most frequent problems were contamination (74
      incidents) and issues related to packaging (98 incidents). Formulations for
      parenteral administration (117 incidents) were the formulation most frequently
      affected. There were 11 falsified medicines, as defined by the MHRA, reported
      over the 11-year period. The number of defective medicines reported by the MHRA
      increased 10-fold from 5 in 2001 to 50 in 2011. CONCLUSIONS: Substandard
      medicines are a significant problem in the UK. It is uncertain whether the
      increasing number of reports relates to improved detection or an increase in the
      number of substandard medicines.

PMID- 23883883
TI  - High blood pressure during pregnancy is associated with future cardiovascular
      disease: an observational cohort study.
AB  - OBJECTIVES: The study aimed to determine if having a hypertensive disorder of
      pregnancy (HDP) is a risk factor for future cardiovascular disease (CVD),
      independent of age and body mass index (BMI). DESIGN: Data were sourced from the
      baseline questionnaire of the 45 and Up Study, Australia, an observational cohort
      study. SETTING: Participants were randomly selected from the Australian Medicare
      Database within New South Wales. PARTICIPANTS: A total of 84 619 women were
      eligible for this study, of which 71 819 were included. These women had given
      birth between the ages of 18 and 45 years, had an intact uterus and ovaries, and
      had not been diagnosed with high blood pressure prior to their first pregnancy.
      RESULTS: HDP was associated with higher odds of having high blood pressure (<58
      years: adjusted OR 3.79, 99% CI 3.38 to 4.24; p<0.001 and >=58 years: 2.83, 2.58
      to 3.12; p<0.001) and stroke (<58 years: 1.69, 1.02 to 2.82; p=0.008 and >=58
      years: 1.46, 1.13 to 1.88; p<0.001) in later life. Women with HDP had a younger
      age of onset of high blood pressure (45.6 vs 54.8 years, p<0.001) and stroke (58
      vs 62.5 years, p<0.001). Women who had HDP and whose present day BMI was <25 had
      significantly higher odds of having high blood pressure, compared with women who
      were normotensive during pregnancy (<58 years: 4.55, 3.63 to 5.71; p<0.001 and
      >=58 years, 2.94, 2.49 to 3.47; p<0.001). Women who had HDP and a present day
      BMI>=25 had significantly increased odds of high blood pressure (<58 years:
      12.48, 10.63 to 14.66; p<0.001 and >=58 years, 5.16, 4.54 to 5.86; p<0.001),
      compared with healthy weight women with a normotensive pregnancy. CONCLUSIONS:
      HDP is an independent risk factor for future CVD, and this risk is further
      exacerbated by the presence of overweight or obesity in later life.

PMID- 23883884
TI  - Opportunities and challenges for enhancing preconception health in primary care:
      qualitative study with women from ethnically diverse communities.
AB  - OBJECTIVE:  There is a growing interest in developing and offering more
      systematic preconception healthcare. However, it is unclear how this might be
      regarded by ethnically diverse communities at higher risk of poor maternal and
      child health outcomes. We sought to explore perceptions about preconception
      health and care among women from these communities to identify opportunities and
      challenges for intervention development in primary care. DESIGN: Qualitative
      study using focus groups and semistructured interviews. SETTING: Ethnically
      diverse and socially disadvantaged community settings of the UK. PARTICIPANTS: 41
      women aged 18-45 years, of Pakistani, Indian, Caribbean, African, White and mixed
      ethnic origin, participating in nine focus groups, half of whom (n=19) had one-to
      one follow-up telephone interviews. RESULTS: Women had modest or poor awareness
      of preconception health issues. They perceived these could be addressed in
      primary care, particularly if raised within a range of clinically 'relevant'
      consultations, such as for contraception, or when opportune for individuals in
      their social context. However, challenges for engaging women in preconception
      care more routinely were underlined. These included little prevailing culture of
      preparing for pregnancy and the realities of their pregnancies often being
      unplanned; and, for those planning pregnancy, sensitivity and maintaining secrecy
      when trying to conceive. A preference for female professionals, engaging men, and
      enhancing access for younger people or women less disposed to general practice,
      in educational and other settings were highlighted. CONCLUSIONS: Raising
      preconception health when this has heightened clinical or social resonance for
      women may hold promise for initiating more systematic intervention. In primary
      care this could offer greater potential to directly engage those with low
      awareness or not considering pregnancy, while enlarging opportunity for others
      who may be seeking to conceive. Promoting 'preparation for pregnancy' more widely
      might form part of healthcare and education over the life course. Further
      intervention development research exploring these possibilities, including their
      feasibility and acceptability is needed.

PMID- 23883885
TI  - Virtual colleagues, virtually colleagues--physicians' use of Twitter: a
      population-based observational study.
AB  - OBJECTIVE: To investigate potential violations of patient confidentiality or
      other breaches of medical ethics committed by physicians and medical students
      active on the social networking site Twitter. DESIGN: Population-based cross
      sectional observational study. SETTING: The social networking site Twitter
      (Swedish-speaking users, n=298819). POPULATION: Physicians and medical students
      (Swedish-speaking users, n=237) active on the social networking site Twitter
      between July 2007 and March 2012. MAIN OUTCOME MEASURE: Postings that reflect
      unprofessional behaviour and ethical breaches among physicians and medical
      students. RESULTS: In all, 237 Twitter accounts were established as held by
      physicians and medical students and a total of 13 780 tweets were analysed by
      content. In all, 276 (1.9%) tweets were labelled as 'unprofessional'. Among
      these, 26 (0.2%) tweets written by 15 (6.3%) physicians and medical students
      included information that could violate patient privacy. No information on the
      personal ID number or names was disclosed, but parts of the patient documentation
      or otherwise specific indicatory information on patients were found.
      Unprofessional tweets were more common among users writing under a pseudonym and
      among medical students. CONCLUSIONS: In this study of physicians and medical
      students on Twitter, we observed potential violations of patient privacy and
      other breaches of medical ethics. Our findings underline that every physician and
      medical student has to consider his or her presence on social networking sites.
      It remains to be investigated if the introduction of social networking site
      guidelines for medical professionals will improve awareness.

PMID- 23883886
TI  - 'Have you seen what is on Facebook?' The use of social networking software by
      healthcare professions students.
AB  - OBJECTIVE: The use of social networking software has become ubiquitous in our
      society. The aim of this study was to explore the attitudes and experiences of
      healthcare professional students using Facebook at our school, to determine if
      there is a need for development of policy to assist students in this area.
      DESIGN: A mixed-methods approach was employed, using semistructured interviews to
      identify themes which were explored using an online survey. A combination of
      descriptive statistics and thematic analysis was used for analysis. SETTING:
      Healthcare professions education programmes at a large Canadian university.
      PARTICIPANTS: Students of medicine, nursing, pharmacy, speech and language
      pathology, occupational therapy, physical therapy, dentistry, dental hygiene and
      medical laboratory Science were invited to participate. 14 participants were
      interviewed, and 682 participants responded to an online survey; the female:male
      balance was 3 : 1. RESULTS: 14 interviews were analysed in-depth, and 682
      students responded to the survey (17% response rate). 93% reported current
      Facebook use. Themes identified included patterns of use and attitudes to
      friendship, attitudes to online privacy, breaches of professional behaviour on
      Facebook and attitudes to guidelines relating to Facebook use. A majority
      considered posting of the following material unprofessional: use of
      alcohol/drugs, crime, obscenity/nudity/sexual content, patient/client
      information, criticism of others. 44% reported seeing such material posted by a
      colleague, and 27% reported posting such material themselves. A majority of
      participants agreed that guidelines for Facebook use would be beneficial.
      CONCLUSIONS: Social networking software use, specifically Facebook use, was
      widespread among healthcare students at our school who responded to our survey.
      Our results highlight some of the challenges which can accompany the use of this
      new technology and offer potential insights to help understand the pedagogy and
      practices of Facebook use in this population, and to help students navigate the
      dilemmas associated with becoming 21st century healthcare professionals.

PMID- 23883887
TI  - Suboptimal prescribing of proton-pump inhibitors in low-dose aspirin users: a
      cohort study in primary care.
AB  - OBJECTIVE: Determine the adherence to recommendations of concomitant proton-pump
      inhibitor (PPI) treatment in regular low-dose of aspirin (LDASA) users, taking
      factors associated with the probability of receiving a PPI into account. DESIGN:
      Cohort study. SETTING: Data were obtained from 120 Dutch primary care centres
      participating in the Netherlands Information Network of Primary Care (LINH).
      PARTICIPANTS: Patients 18 years and older who were regularly prescribed LDASA (30
      325 mg) in 2008-2010 were included. MAIN OUTCOME MEASURES: Regular medication use
      was defined as receiving each consecutive prescription within 6 months after the
      previous one. Based on national guidelines, we categorised LDASA users into low
      and high gastrointestinal (GI) risk. A multilevel multivariable logistic
      regression analysis was applied to identify patient characteristics that
      influenced on the probability of regular PPI prescriptions. RESULTS: We
      identified 12 343 patients who started LDASA treatment, of whom 3213 (26%) were
      at increased risk of GI complications. In this group, concomitant regular use of
      PPI was 46%, 36% did not receive PPI prescriptions and 18% obtained prescriptions
      irregularly (p<0.0001). The chance to obtain regularly PPI prescriptions versus
      no PPI was significantly influenced by, among others, previous GI complications
      (OR 13.9 (95% CI 11.8 to 16.4)), use of non-steroidal anti-inflammatory drugs (OR
      5.2 (4.3 to 6.3)), glucocorticosteroids (6.1 (4.6 to 8.0)), selective serotonin
      reuptake inhibitors (9.1 (6.7 to 12.2)), drugs for functional GI disorders (2.4
      (1.9 to 3.0)) and increased age. CONCLUSIONS: Primary care physicians do not
      fully adhere to the current recommendations to prescribe PPIs regularly to LDASA
      users with an increased GI risk. More than 50% of the patients with an increased
      GI risk are not treated sufficiently with a concomitant PPI, increasing the risk
      of GI side effects. This finding underlines the necessity to consider merging
      recommendations into one common, standard and frequently used recommendation by
      primary care physicians.

PMID- 23883888
TI  - Transient neurological symptoms in the older population: report of a prospective
      cohort study--the Medical Research Council Cognitive Function and Ageing Study
      (CFAS).
AB  - OBJECTIVE: Transient ischaemic attack (TIA) is a recognised risk factor for
      stroke in the older population requiring timely assessment and treatment by a
      specialist. The need for such TIA services is driven by the epidemiology of
      transient neurological symptoms, which may not be caused by TIA. We report
      prevalence and incidence of transient neurological symptoms in a large UK cohort
      study of older people. DESIGN: Longitudinal cohort study SETTING: The Medical
      Research Council Cognitive Function and Aging Study (CFAS) is a population
      representative study based on six centres across England and Wales. PARTICIPANTS:
      Random samples of people in their 65th year were obtained from Family Health
      Service Authority lists. The participation rate was 80% (n=13 004). Interview at
      baseline included questions about stroke and three transient neurological
      symptoms, repeated in a subsample after 2 years. Patients were flagged for
      mortality. MAIN OUTCOME MEASURES: Prevalence and 2-year incidence of transient
      neurological symptoms. RESULTS: In 11 903 participants without a history of
      stroke, 271 (2.3%) reported transient problems with speech, 872 (7.6%) with sight
      and 596 (5.1%) weakness in a limb with 1456 (12.7%) reporting at least one
      symptom. Of those reinterviewed (n=6748), 675 (9.8%) reported at least one
      symptom over 2 years. CONCLUSIONS: Lifetime prevalence and incidence of transient
      neurological symptoms in people aged 65 years and over is high and is
      substantially greater than the incidence of TIA in hospital-based and population
      based studies. These high rates of transient neurological symptoms in the
      community in the older population should be considered when planning TIA
      services.

PMID- 23883889
TI  - The small eye phenotype in the EPIC-Norfolk eye study: prevalence and visual
      impairment in microphthalmos and nanophthalmos.
AB  - OBJECTIVE: To describe the prevalence and phenotypic characteristics of small
      eyes in the European Prospective Investigation of Cancer (EPIC)-Norfolk Eye
      Study. DESIGN: Community cross-sectional study. SETTING: East England population
      (Norwich, Norfolk and surrounding area). PARTICIPANTS: 8033 participants aged 48
      92 years old from the EPIC-Norfolk Eye Study, Norfolk, UK with axial length
      measurements. Participants underwent a standardised ocular examination including
      visual acuity (LogMAR), ocular biometry, non-contact tonometry, autorefraction
      and fundal photography. A small eye phenotype was defined as a participant with
      one or both eyes with axial length of <21 mm. OUTCOME MEASURES: Prevalence of
      small eyes, proportion with visual impairment, demographic and biometric factors.
      RESULTS: Ninety-six participants (1.20%, 95% CI 0.98% to 1.46%) had an eye with
      axial length less than 21 mm, of which 74 (77%) were women. Prevalence values for
      shorter axial lengths were <20 mm: 0.27% (0.18% to 0.41%); <19 mm: 0.17% (0.11%
      to 0.29%); <18 mm: 0.14% (0.08% to 0.25%). Two participants (2.1%) had low vision
      (presenting visual acuity >0.48 LogMAR) and one participant was blind (>1.3
      LogMAR). The prevalence of unilateral visual impairment was higher in
      participants with a small eye. Multiple logistic regression modelling showed
      presence of a small eye to be significantly associated with shorter height, lower
      body mass index, higher systolic blood pressure and lower intraocular pressure.
      CONCLUSIONS: The prevalence of people with small eyes is higher than previously
      thought. While small eyes were more common in women, this appears to be related
      to shorter height and lower body mass index. Participants with small eyes were
      more likely to be blind or to have unilateral visual impairment.

PMID- 23883890
TI  - A parallel-group, randomised controlled trial of a multimedia, self-directed,
      coping skills training intervention for patients with cancer and their partners:
      design and rationale.
AB  - INTRODUCTION: Coping skills training interventions have been found to be
      efficacious in helping both patients and their partners manage the physical and
      emotional challenges they face following a cancer diagnosis. However, many of
      these interventions are costly and not sustainable. To overcome these issues, a
      self-directed format is increasingly used. The efficacy of self-directed
      interventions for patients has been supported; however, no study has reported on
      the outcomes for their partners. This study will test the efficacy of Coping
      Together-a multimedia, self-directed, coping skills training intervention for
      patients with cancer and their partners. METHODS AND ANALYSIS: The proposed three
      group, parallel, randomised controlled trial will recruit patients diagnosed in
      the past 4 months with breast, prostate, colorectal cancer or melanoma through
      their treating clinician. Patients and their partners will be randomised to (1) a
      minimal ethical care (MEC) condition-selected Cancer Council New South Wales
      booklets and a brochure for the Cancer Council Helpline, (2) Coping-Together
      generic-MEC materials, the six Coping-Together booklets and DVD, the Cancer
      Council Queensland relaxation audio CD and login to the Coping-Together website
      or (3) Coping-Together tailored-MEC materials, the Coping-Together DVD, the login
      to the website and only those Coping-Together booklet sections that pertain to
      their direct concerns. Anxiety (primary outcome), distress, depression, dyadic
      adjustment, quality of life, illness or caregiving appraisal, self-efficacy and
      dyadic and individual coping will be assessed before receiving the study material
      (ie, baseline) and again at 3, 6 and 12 months postbaseline. Intention-to-treat
      and per protocol analysis will be conducted. ETHICS AND DISSEMINATION: This study
      has been approved by the relevant local area health and University ethics
      committees. Study findings will be disseminated not only through peer-reviewed
      publications and conference presentations but also through educational outreach
      visits, publication of lay research summaries in consumer newsletters and
      publications targeting clinicians. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry ACTRN12613000491763 (03/05/2013).

PMID- 23883892
TI  - Where do we go from here? Preface. US Military Health System Research Symposium,
      August 2013.

PMID- 23883891
TI  - Daily electronic self-monitoring of subjective and objective symptoms in bipolar
      disorder--the MONARCA trial protocol (MONitoring, treAtment and pRediCtion of
      bipolAr disorder episodes): a randomised controlled single-blind trial.
AB  - INTRODUCTION: Electronic self-monitoring of affective symptoms using cell phones
      is suggested as a practical and inexpensive way to monitor illness activity and
      identify early signs of affective symptoms. It has never been tested in a
      randomised clinical trial whether electronic self-monitoring improves outcomes in
      bipolar disorder. We are conducting a trial testing the effect of using a
      Smartphone for self-monitoring in bipolar disorder. METHODS: We developed the
      MONARCA application for Android-based Smartphones, allowing patients suffering
      from bipolar disorder to do daily self-monitoring-including an interactive
      feedback loop between patients and clinicians through a web-based interface. The
      effect of the application was tested in a parallel-group, single-blind randomised
      controlled trial so far including 78 patients suffering from bipolar disorder in
      the age group 18-60 years who were given the use of a Smartphone with the MONARCA
      application (intervention group) or to the use of a cell phone without the
      application (placebo group) during a 6-month study period. The study was carried
      out from September 2011. The outcomes were changes in affective symptoms
      (primary), social functioning, perceived stress, self-rated depressive and manic
      symptoms, quality of life, adherence to medication, stress and cognitive
      functioning (secondary and tertiary). ANALYSIS: Recruitment is ongoing. ETHICS:
      Ethical permission has been obtained. DISSEMINATION: Positive, neutral and
      negative findings of the study will be published. REGISTRATION DETAILS: The trial
      is approved by the Regional Ethics Committee in The Capital Region of Denmark (H
      2-2011-056) and The Danish Data Protection Agency (2013-41-1710). The trial is
      registered at ClinicalTrials.gov as NCT01446406.

PMID- 23883893
TI  - On the shoulders of giants...

PMID- 23883894
TI  - Point-of-injury use of reconstituted freeze dried plasma as a resuscitative
      fluid: a special report for prehospital trauma care.

PMID- 23883895
TI  - Evolution of biomedical research during combat operations.
AB  - BACKGROUND: The implementation of a human research protection program in
      Afghanistan and the mobilization of the combat casualty research team have made
      it possible to design and efficiently conduct multifaceted, multisite, and
      prospective research studies in a combat environment. Still, to conduct research
      in such an environment, several unique challenges must be overcome. METHODS: This
      article describes the development and conduct of three ongoing trauma-related
      biomedical research studies in Afghanistan, highlighting the challenges and
      lessons learned within the context of these studies. RESULTS: Key challenges
      include the process of developing and getting approval for in-theater research
      protocols, the informed consent process, and logistics of conducting a biomedical
      research study in an austere environment. Despite these challenges, important
      lessons learned that can contribute to the success of a protocol include the need
      for clear operating procedures, judicious selection for which data points must be
      collected in-theater, and the importance anticipating the "fog and friction" of
      war. CONCLUSION: As we continue the journey toward more sophisticated research
      capabilities in combat, this article will help inform the design and conduct of
      future research performed in a theater of war. Conducting biomedical research in
      a combat zone is an important but difficult element of military medicine.

PMID- 23883896
TI  - Extracorporeal organ support following trauma: the dawn of a new era in combat
      casualty critical care.

PMID- 23883897
TI  - Forward aeromedical evacuation: a brief history, lessons learned from the Global
      War on Terror, and the way forward for US policy.

PMID- 23883898
TI  - The Remote Trauma Outcomes Research Network: rationale and methodology for the
      study of prolonged out-of-hospital transport intervals on trauma patient outcome.

PMID- 23883899
TI  - Intramuscular transplantation and survival of freshly isolated bone marrow cells
      following skeletal muscle ischemia-reperfusion injury.
AB  - BACKGROUND: Delayed treatment cellular therapies offer an attractive means to
      treat extremity injuries involving acute skeletal muscle ischemia-reperfusion
      injury (I/R). Bone marrow is a rich source of stem and progenitor cells with the
      potential to improve skeletal muscle regeneration. The extent to which bone
      marrow cells (BMCs) may be useful for I/R is not known. The purposes of this
      study were twofold: (1) to evaluate BMC survival following intramuscular
      injection 0, 2, 7, and 14 days after injury and (2) to determine whether BMCs
      improve functional recovery following I/R. METHODS: Magnetic-activated cell
      sorting was used to isolate lineage-negative (Lin-) BMCs and enrich for stem and
      progenitor cells. To evaluate in vivo cell survival following I/R, Lin- BMCs were
      injected intramuscularly 0, 2, 7, and 14 days after I/R, and bioluminescent
      imaging was performed for up to 28 days after cell injections. To assess their
      ability to improve muscle regeneration, intramuscular injections were performed 2
      days after injury, and in vivo muscle function was assessed 14 days later.
      RESULTS: Lin- BMCs survived throughout the study period regardless of the timing
      of delivery. Intramuscular injection of Lin- BMCs did not improve maximal
      isometric torque (300 Hz); however, both saline-injected and Lin- BMC-injected
      muscles exhibited an increase in the twitch-tetanus ratio, suggesting that damage
      incurred with the intramuscular injections may have had deleterious consequences
      for functional recovery. CONCLUSION: Although BMCs injected intramuscularly
      survived cell transplantation, they failed to improve muscle function following
      I/R. The ability of BMCs to persist in injured muscle following I/R lends to the
      possibility that with further development, their full potential can be realized.

PMID- 23883900
TI  - Comparison of novel hemostatic dressings with QuikClot combat gauze in a
      standardized swine model of uncontrolled hemorrhage.
AB  - BACKGROUND: Uncontrolled hemorrhage is the leading cause of preventable death on
      the battlefield. The development, testing, and application of novel hemostatic
      dressings may lead to a reduction of prehospital mortality through enhanced point
      of-injury hemostatic control. This study aimed to determine the efficacy of
      currently available hemostatic dressings as compared with the current Committee
      for Tactical Combat Casualty Care Guidelines standard of treatment for hemorrhage
      control (QuikClot Combat Gauze [QCG]). METHODS: The femoral artery of
      anesthetized Yorkshire pigs was isolated and punctured. Free bleeding was allowed
      to proceed for 45 seconds before packing of QCG, QuikClot Combat Gauze XL (QCX),
      Celox Trauma Gauze (CTG), Celox Gauze (CEL), or HemCon ChitoGauze (HCG), into the
      wound. After 3 minutes of applied, direct pressure, fluid resuscitation was
      administered to elevate and maintain a mean arterial pressure of 60 mm Hg or
      greater during the 150-minute observation time. Animal survival, hemostasis, and
      blood loss were measured as primary end points. Hemodynamic and physiologic
      parameters, along with markers of coagulation, were recorded and analyzed.
      RESULTS: Sixty percent of QCG-treated animals (controls) survived through the 150
      minute observation period. QCX, CEL, and HCG were observed to have higher rates
      of survival in comparison to QCG (70%, 90%, and 70% respectively), although these
      results were not found to be of statistical significance in pairwise comparison
      to QCG. Immediate hemostasis was achieved in 30% of QCG applications, 80% of QCX,
      70% of CEL, 60% of HCG, and 30% of CTG-treated animals. Posttreatment blood loss
      varied from an average of 64 mL/kg with CTG to 29 mL/kg with CEL, but no
      significant difference among groups was observed. CONCLUSION: These results
      suggest that the novel hemostatic devices perform at least as well as the current
      Committee on Tactical Combat Casualty Care standard for point-of-injury
      hemorrhage control. Despite their different compositions and sizes, the lack of
      clear superiority of any agent suggests that contemporary hemostatic dressing
      technology has potentially reached a plateau for efficacy.

PMID- 23883901
TI  - Performance improvement evaluation of forward aeromedical evacuation platforms in
      Operation Enduring Freedom.
AB  - BACKGROUND: The following three helicopter-based medical evacuation platforms
      operate in Southern Afghanistan: the US Army emergency medical technician (basic)
      led DUSTOFF, US Air Force paramedic-led PEDRO, and UK physician-led medical
      emergency response team (MERT). Nearly 90% of battlefield deaths occur in the
      prehospital phase, comparative outcomes for these en route care platforms are
      unknown. The objective of this investigation was to characterize the nature of
      injuries in patients transported by three evacuation platforms. In addition, it
      aimed to compare observed versus predicted mortality among these provider groups.
      METHODS: A performance improvement study involving 975 coalition patients injured
      in Southern Afghanistan, transported from the point of injury to a military
      hospital, was performed. All patients were alive on admission with prehospital
      documentation recorded in the US Department of Defense Trauma Registry from June
      2009 to June 2011. The main outcome measure was in-hospital mortality and
      observed versus predicted (Trauma and Injury Severity Score [TRISS]) survival
      were the primary end points. RESULTS: MERT transported more amputation and
      polytrauma casualties and included patients with higher mean Injury Severity
      Score (ISS) compared with PEDRO and DUSTOFF (16 [13] vs. 11 [10] and 10 [10]
      respectively; p < 0.001). DUSTOFF was excluded from the subgroup analysis owing
      to insufficient numbers of severely injured casualties with only one death. The
      overall mortality for MERT and PEDRO was similar (4.2% vs. 4.6%, p = 0.967).
      Stratifying by ISS, there was lower mortality in MERT compared with PEDRO in the
      range of 20 to 29 (4.8% vs. 16.2%, p = 0.021). The observed mortality among PEDRO
      casualties was as predicted with the exception of the range of 20 to 29, while
      mortality in MERT was lower than predicted for all ISS groups with greater than
      10. CONCLUSION: MERT achieves greater than predicted survival, which may be
      related to the additional capabilities onboard. This supports the adoption of a
      versatile medical evacuation system with scalable crew and equipment
      configurations that adapt to meet the medical, tactical, and operational needs of
      future conflicts.

PMID- 23883902
TI  - Analysis of remote trauma transfers in South Central Texas with comparison with
      current US combat operations: results of the RemTORN-I study.
AB  - BACKGROUND: This study aimed to analyze demographic, epidemiologic, temporal, and
      outcome data from an integrated trauma registry of patients undergoing initial
      stabilization and transfer within a mature domestic trauma network; compare data
      with a companion subset from the Department of Defense Trauma Registry. Texas
      Trauma Service Area-P is composed of 25 counties, 15 rural Level IV trauma
      centers (no acute care surgery), and two Level I trauma centers. METHODS: This
      study has a retrospective cohort design. We hypothesize that Injury Severity
      Scores (ISSs), time intervals, and other clinical indicators would be
      complimentary to contemporary combat casualties. Inclusion criteria include age
      18 years to 80 years, transferred from Level IV to Level I trauma center, or
      expired en route. RESULTS: A total of 543 subjects (84%) met the criteria and
      were analyzed. Averages and confidence intervals were as follows: age of 40 years
      (38-41 years), males at 81%, ISS of 10 (10-11), intensive care unit stay of 2
      days (1-3 days), and hospital stay of 5 days (4-6 days). Mechanisms of injury
      were as follows: penetrating (15%), blunt weapon (19%), stabs (9%), burns (5%),
      and gunshots (5%). Eight percent received blood within the first 24 hours.
      Survival was at 98%. Time intervals (95% confidence interval) were as follows:
      prehospital at 1:43 (1:29-1:58), Level IV dwell time at 3:17 (3:06-3:28),
      interfacility transfer at 1:43 (1:36-1:49), and total at 6:39 (6:20-6:58).
      RemTORN cases were older, spent longer time en route to Level I, and had ISS
      similar to combat casualties. Rates of blood transfusion in the first 24 hours
      and survival were similar in order of magnitude. CONCLUSION: The RemTORN platform
      is operational. Demographic, epidemiologic, and temporal characteristics as
      observed will support clinical investigations of traumatic coagulopathy, shock,
      and potential interventions before Level I arrival. Results of such
      investigations will likely be applicable to the contemporary and future
      battlefield.

PMID- 23883903
TI  - Morphometric analysis of torso arterial anatomy with implications for
      resuscitative aortic occlusion.
AB  - BACKGROUND: Hemorrhage is a leading cause of death in military and civilian
      trauma. Despite the importance of the aorta as a site of hemorrhage control and
      resuscitative occlusion, detailed knowledge of its morphometry is lacking. The
      objective of this study was to characterize aortic morphometry in a trauma
      population, including quantification of distances as well as and diameters and
      definition of relevant aortic zones. METHODS: Center line measures were made
      (Volume Viewer) from contrast computed tomography (CT) scans of male trauma
      patients (18-45 years). Aortic zones were defined based on branch arteries. Zone
      I includes left subclavian to celiac; Zone II includes celiac to caudal renal;
      Zone III includes caudal renal to aortic bifurcation. Zone lengths were
      calculated and correlated to a novel external measure of torso extent (symphysis
      pubis to sternal notch). RESULTS: Eighty-eight males (mean [SD], 28 [4] years)
      had CT scans for the study. The median (interquartile range) lengths (mm) of
      Zones I, II, and III were 210 mm (202-223 mm), 33 mm (28-38 mm), and 97 mm (91
      103 mm), respectively. Median aortic diameters at the left subclavian, celiac,
      and lowest renal arteries were 21 mm (20-23 mm), 18 mm (16-19 mm), and 15 mm (14
      16 mm), respectively, and the terminal aortic diameter was 14 mm (13-15 mm). The
      correlation of determination for descending aortic length (all zones) against
      torso extend was r = 0.454. CONCLUSION: This study provides a morphometric
      analysis of the aorta in a male population, demonstrating consistency of length
      and diameter while defining distinct axial zones. Findings suggest that center
      line aortic distances correlate with a simple, external measure of torso extent.
      Morphometric study of the aorta using CT data may facilitate the development and
      implementation of occlusion techniques to manage noncompressible torso, pelvic,
      and junctional femoral hemorrhage.

PMID- 23883904
TI  - Feasibility of blind aortic catheter placement in the prehospital environment to
      guide resuscitation in cardiac arrest.
AB  - BACKGROUND: Aortic catheter-based resuscitation therapies are emerging with
      laboratory investigations showing benefit in models of trauma-related
      noncompressible torso hemorrhage and nontraumatic cardiac arrest. For these
      investigational aortic catheter-based therapies to reach their greatest potential
      clinical benefit, the ability to initiate them in the prehospital setting will be
      important. Feasibility of prehospital aortic catheterization without imaging
      capability supports this potential and is described in this report. METHODS: A
      physician prehospital response system was created in cooperation with the local
      emergency medical services system to provide invasive hemodynamic monitoring
      during cardiac arrest. Physicians were dispatched to all known or suspected
      prehospital cardiac arrests covered by the emergency medical services system.
      Physicians responded with a specialized vascular catheterization pack and a
      monitor with invasive pressure monitoring capability. The physicians performed
      blind thoracic aortic and central venous catheterizations in cardiac arrest
      patients in the prehospital setting to measure coronary perfusion pressure, to
      optimize closed-chest cardiopulmonary resuscitation technique, and to administer
      intra-aortic epinephrine. RESULTS: During a 2-year period, 22 medical cardiac
      arrest patients underwent prehospital invasive hemodynamic monitoring to guide
      resuscitation. Most patients had both aortic and central venous catheters
      inserted. The combination of intra-aortic epinephrine and adjustments in closed
      chest cardiopulmonary resuscitation technique resulted in improved coronary
      perfusion pressure. Return of spontaneous circulation with survival to hospital
      admission was achieved in 50% (11 of 22) of these patients. CONCLUSION: This
      report demonstrates the feasibility of successful blind aortic and central venous
      catheterizations in the prehospital environment and supports the potential
      feasibility of other emerging aortic catheter-based resuscitation therapies.

PMID- 23883905
TI  - Prehospital intubation success rates among Israel Defense Forces providers:
      epidemiologic analysis and effect on doctrine.
AB  - BACKGROUND: Advanced airway management is composed of a set of vital yet
      potentially difficult skills for the prehospital provider, with widely different
      clinical guidelines. In the military setting, there are few data available to
      inform guideline development. We reevaluated our advanced airway protocol in
      light of our registry data to determine if there were a preferred maximum number
      of endotracheal intubation (ETI) attempts; our success with cricothyroidotomy
      (CRIC) as a backup procedure; and whether there were cases where advanced airway
      interventions should possibly be avoided. METHODS: This is a descriptive,
      registry-based study conducted using records of the Israel Defense Forces Trauma
      Registry at the research section of the Trauma and Combat Medicine Branch,
      Surgeon General's Headquarters. We included all casualties for whom ETI was the
      initial advanced airway maneuver, and the number of ETI attempts was known.
      Descriptive statistics were used. RESULTS: Of 5,553 casualties in the Israel
      Defense Forces Trauma Registry, 406 (7.3%) met the inclusion criteria. Successful
      ETI was performed in 317 casualties (78%) after any number of ETI attempts; an
      additional 46 (11%) underwent CRIC, and 43 (11%) had advanced airway efforts
      discontinued. ETI was successful in 45%, 36%, and 31% of the first, second, and
      third attempts, respectively, with an average of 28% success over all subsequent
      attempts. CRIC was successful in 43 (93%) of 46 casualties in whom it was
      attempted. Of the 43 casualties in whom advanced airway efforts were
      discontinued, 29 (67%) survived to hospital discharge. CONCLUSION: After the
      first ETI attempt, success with subsequent attempts tended to fall, with minimal
      improvement in overall ETI success seen after the third attempt. Because CRIC
      exhibited excellent success as a backup airway modality, we advocate controlling
      the airway with CRIC if ETI efforts have failed after two or three attempts. We
      recommend that providers reevaluate whether definitive airway control is truly
      necessary before each attempt to control the airway.

PMID- 23883906
TI  - Promoting early diagnosis of hemodynamic instability during simulated hemorrhage
      with the use of a real-time decision-assist algorithm.
AB  - BACKGROUND: This study aimed to test the hypothesis that the addition of a real
      time decision-assist machine learning algorithm by emergency medical system
      personnel could shorten the time needed to identify an unstable patient during a
      hemorrhage profile as compared with vital sign information alone. METHODS: Fifty
      emergency medical team-paramedics from a large, urban fire department
      participated as subjects. Subjects viewed a monitor screen on two occasions as
      follows: (1) display of standard vital signs alone and (2) with the addition of
      an index (Compensatory Reserve Index) associated with estimated central blood
      volume status. The subjects were asked to push a computer key at any point in the
      sequence they believed the patient had become unstable based on information
      provided by the monitor screen. The average difference in time to identify
      hemodynamic instability between experimental and control groups was assessed by
      paired, two-tailed t test and reported with 95% confidence intervals (95% CI).
      RESULTS: The mean (SD) amount of time required to identify an unstable patient
      was 18.3 (4.1) minutes (95% CI, 17.2-19.4 minutes) without the algorithm and 10.7
      (4.2) minutes (95% CI, 9.5-11.9 minutes) with the algorithm (p < 0.001).
      CONCLUSION: In a simulated patient encounter involving uncontrolled hemorrhage,
      the use of a monitor that estimates central blood volume loss was associated with
      early identification of impending hemodynamic instability. Physiologic monitors
      capable of early identification and estimation of the physiologic capacity to
      compensate for blood loss during hemorrhage may enable optimal guidance for
      hypotensive resuscitation. They may also help identify casualties benefitting
      from forward administration of plasma, antifibrinolytics and procoagulants in a
      remote damage-control resuscitation model.

PMID- 23883907
TI  - Model-based prediction of autoregulatory exhaustion in response to lower-body
      negative pressure-induced shock.
AB  - BACKGROUND: We assessed the ability of a normalized autonomic nervous system
      (ANS) stress measure defined as an increase in the percentage of pulse rate from
      a baseline homeostasis state to identify corresponding changes in circulating
      blood volume to quantitatively recognize hypovolemia and predict subsequent
      autoregulatory exhaustion. Autoregulatory exhaustion is defined as the point
      where decreased circulatory volume exceeds the compensatory mechanism capacity to
      maintain flow and pressure. We derived frequency-based measures of pulse rate and
      pulse strength using a reflective pulse oximeter waveform of a
      photoplethysmograph placed on the forehead. METHODS: This study was performed at
      the Penn State Heart and Vascular Institute, Hershey, Pennsylvania, in June 2010.
      Ten healthy subjects (5 each male and female) were placed supine in a lower-body
      negative-pressure chamber to induce central volume loss. Systolic blood pressure
      was continuously measured, and a value of less than 90 mm Hg defined
      autoregulatory exhaustion. Derived measures of circulating blood volume were
      compared with echocardiographic measures to access photoplethysmograph-derived
      circulatory volume measure relative to traditional cardiac hemodynamics. RESULTS:
      All 10 subjects produced consistent patterns of response characterized as a
      progressively increasing ANS stress in response to increasing lower-body negative
      pressure. Three subjects exhibited autoregulatory exhaustion, and ANS stress
      increased markedly on the step before displaying hypotension in these subjects
      but not the others. CONCLUSION: Results demonstrate the potential to use model
      based measures to serve as a definitive presymptom predictive tool to recognize
      an impending hypovolemic condition, making this approach suitable for chronic
      care or for the management of hemodialysis patient where resting baseline
      measures can be obtained.

PMID- 23883908
TI  - Physiologic mechanisms underlying the failure of the "shock index" as a tool for
      accurate assessment of patient status during progressive simulated hemorrhage.
AB  - BACKGROUND: Shock index (SI), the ratio of heart rate (HR) to systolic arterial
      pressure (SAP), is a metric often used to diagnose patients at risk of impending
      cardiovascular instability and hemorrhagic shock. We hypothesized that if SI
      reflected impending cardiovascular instability and shock in an individual, then:
      (1) elevations in SI and HR would be greater in individuals with low tolerance
      (LT) to progressive lower-body negative-pressure (LBNP) compared with individuals
      with high tolerance (HT), and (2) LT would be associated with greater vagal
      withdrawal of the baroreflex sensitivity (BRS) compared with HT. METHODS: A total
      of 187 healthy subjects (HT, 125; LT, 62) underwent exposure to LBNP until a SAP
      of less than 80 mm Hg (instability) was achieved. HR and SAP were used to
      calculate SI, and BRS was determined from spontaneous fluctuations in R-R
      interval and diastolic arterial pressure. Maximal cardiac vagal withdrawal was
      calculated as the difference between BRS at baseline and BRS at 100% LBNP
      tolerance. RESULTS: Contrary to our hypothesis, SI at 60%, 80%, and 100% LBNP
      tolerance in LT (0.59 +/- 0.03, 0.73 +/- 0.04, and 0.97 +/- 0.06, respectively)
      was lower (p <= 0.002) than SI in HT subjects at the same levels (0.66 +/- 0.03,
      0.84 +/- 0.04, and 1.24 +/- 0.06, respectively). Maximal cardiac vagal withdrawal
      was less (p = 0.045) in LT subjects (11.3 +/- 2.2 ms/mm Hg) compared with HT
      subjects (14.9 +/- 2.5 ms/mm Hg). The sensitivity of SI in identifying impending
      instability (SI, 0.9) at 80% and 100% LBNP tolerance was 13% and 63% in LT
      subjects and 34% and 91% in HT subjects, respectively. CONCLUSION: The low
      sensitivity of the SI observed in LT individuals is associated with a lower
      capacity to withdraw cardiac vagal activity and can lead to an undertriage of
      those patients most likely to develop early hemorrhagic shock.

PMID- 23883909
TI  - "Fluidless" resuscitation with permissive hypotension via impedance threshold
      device therapy compared with normal saline resuscitation in a porcine model of
      severe hemorrhage.
AB  - BACKGROUND: One approach to improve outcomes after trauma and hemorrhage is to
      follow the principles of permissive hypotension by avoiding intravascular
      overpressure and thereby preventing dislodgement of platelet plugs early in the
      clotting process. We hypothesized that augmentation of negative intrathoracic
      pressure (nITP) by treatment with an impedance threshold device would improve
      hemodynamics without compromising permissive hypotension or causing hemodilution,
      whereas aggressive fluid resuscitation with normal saline (NS) would result in
      hemodilution and SBPs that are too high for permissive hypotension and capable of
      clot dislodgement. METHODS: Thirty-four spontaneously breathing anesthetized
      female pigs (30.6 +/- 0.5 kg) were subjected to a fixed 55% hemorrhage over 30
      minutes; block randomized to nITP, no treatment, or intravenous bolus of 1-L NS;
      and evaluated over 30 minutes. Results are reported as mean +/- SEM. RESULTS:
      Average systolic blood pressures (SBPs) (mm Hg) 30 minutes after the study
      interventions were as follows: nITP, 82.1 +/- 2.9; no treatment, 69.4 +/- 4.0; NS
      89.3 +/- 5.2. Maximum SBPs during the initial 15 minutes of treatment were as
      follows: nITP, 88.0 +/- 4.3; no treatment, 70.8 +/- 4.3; and NS, 131 +/- 7.6.
      After 30 minutes, mean pulse pressure (mm Hg) was significantly higher in the
      nITP group (nITP, 32.3 +/- 2.2) versus the no-treatment group (21.5 +/- 1.5
      controls) (p < 0.05), and the mean hematocrit was 25.2 +/- 0.8 in the nITP group
      versus 19 +/- 0.6 in the NS group (p < 0.001). CONCLUSION: In this porcine model
      of hemorrhagic shock, nITP therapy significantly improved SBP and pulse pressure
      for 30 minutes without overcompensation compared with controls with no treatment.
      By contrast, aggressive fluid resuscitation with NS but not nITP resulted in a
      significant rise in SBP to more than 100 mm Hg within minutes of initiating
      therapy that could cause a further reduction in hematocrit and clot dislodgment.

PMID- 23883910
TI  - Early implementation of continuous renal replacement therapy optimizes casualty
      evacuation for combat-related acute kidney injury.
AB  - BACKGROUND: The purpose of this report was to review the initial use and
      feasibility of continuous renal replacement therapy (CRRT) among combat
      casualties in a war zone. Although rapid evacuation to more advanced levels of
      care has emerged as the standard approach, life-threatening sequelae of acute
      kidney injury (AKI) can preclude safe patient evacuation. For the first time in
      US combat casualty care, a sustained, intensivist-led CRRT program was initiated
      during 2010 at an Air Force theater hospital. METHODS: A prospective study of
      consecutive US service members (USSMs) who developed combat-related renal failure
      and underwent CRRT at the Craig Joint Theater Hospital was undertaken. Baseline
      patient characteristics, indications for CRRT, laboratory values, and outcomes
      were evaluated. RESULTS: Nine USSMs were treated during 14-months. All were male,
      with a mean (SD) age of 28 (7) years and mean (SD) Injury Severity Score (ISS) of
      34 (12). The dominant mechanism was blast injury (8 of 9), followed by gunshot
      wound (1 of 9). Most patients were Acute Kidney Injury Network (AKIN) 3 and all
      developed critical hyperkalemia (mean [SD], peak K+ 6.4 [0.4]). The peak plasma
      creatinine ranged from 1.4 mg/dL to 4.2 mg/dL (mean [SD], 3.3 [0.9] mg/dL).
      Patients had a mean (SD) of 17.6 [8.1] hours of CRRT before evacuation to higher
      echelons of care. All USSMs survived to achieve safe evacuation from the combat
      zone to the regional trauma center in Landstuhl, Germany (Landstuhl Regional
      Medical Center). Three patients died of multiorgan failure at Landstuhl Regional
      Medical Center. Six patients survived to undergo additional treatment in the
      United States. CONCLUSION: Intensivist-led CRRT is an effective therapeutic
      adjunct in the treatment of combat-related AKI. Provision of this extracorporeal
      therapy provides physiologic stabilization of casualties who might otherwise
      succumb to the sequelae of combat-related renal failure. These findings suggest
      that a self-sustaining CRRT program can be successfully implemented in combat
      support hospitals.

PMID- 23883911
TI  - Frequency and relevance of acute peritraumatic pulmonary thrombus diagnosed by
      computed tomographic imaging in combat casualties.
AB  - BACKGROUND: Posttraumatic pulmonary embolism is historically diagnosed after
      clinical deterioration within the first week after injury. An increasing
      prevalence of immediate and asymptomatic pulmonary embolism have been reported in
      civilian and military trauma, termed hereafter as acute peritraumatic pulmonary
      thrombus (APPT). The objective of this study was to define the frequency of APPT
      diagnosed by computed tomographic (CT) imaging in wartime casualties. An
      additional objective was to identify factors, which may be associated with this
      radiographic finding METHODS: A 1-year retrospective cohort analysis conducted
      using the US and UK Joint Theater Trauma Registries performed to determine the
      prevalence of and risk factors for the diagnosis of APPT in casualties admitted
      to Bastion Hospital, Afghanistan. APPT imaging characteristics were collected,
      and demographics, injury severity and mechanism, and risk factors were included
      in the analysis. Logistic regression was used to identify factors independently
      associated with APPT. RESULTS: APPT was found in 66 (9.3%) of 708 consecutive
      trauma admissions, which received a CT chest with intravenous contrast as part of
      their initial evaluation. Diagnosis of APPT at the time of injury was made in 23
      patients (3.2%), while thrombus was detected in 43 additional patients (6.1%) at
      the time of reexamination of CT images. Of the APPTs, 47% (n = 31) were central,
      38% (n = 25) were segmental, and 15% (n = 10) were subsegmental. Forty-seven
      percent (n = 31) had bilateral APPT. Logistic regression found presence of deep
      venous thrombosis on admission (odds ratio, 5.75; 95% confidence interval, 2.44
      13.58; p < 0.0001) and traumatic amputation (odds ratio, 2.53; 95% confidence
      interval, 1.10-5.85; p = 0.030) to be independently associated with APPT. All
      APPTs were felt to be incidental and likely would not have required interventions
      such as anticoagulation or vena caval interruption. CONCLUSION: This report is
      the first to characterize acute, peritraumatic pulmonary thrombus in combat
      injured. Nearly 1 in 10 patients with severe wartime injury has findings of
      pulmonary thrombus on CT imaging, although many instances require repeat
      examination of initial images to identify the clot. APPT is a phenomenon of
      severe injury and associated with deep venous thrombosis and lower-extremity
      traumatic amputation. Additional study is needed to characterize the natural
      history of peritraumatic pulmonary thrombus and the indications for
      anticoagulation or vena cava filter devices.

PMID- 23883913
TI  - Microvascular reconstructive surgery in Operations Iraqi and Enduring Freedom:
      the US military experience performing free flaps in a combat zone.
AB  - BACKGROUND: Local nationals with complex wounds resulting from traumatic combat
      injuries during Operations Iraqi Freedom and Enduring Freedom usually must
      undergo reconstructive surgery in the combat zone. While the use of microvascular
      free-tissue transfer (free flaps) for traumatic reconstruction is well documented
      in the literature, various complicating factors exist when these intricate
      surgical procedures are performed in a theater of war. METHODS: The microvascular
      experiences of six military surgeons deployed during a 30-month period between
      2006 and 2011 in Iraq and Afghanistan were retrospectively reviewed. RESULTS:
      Twenty-nine patients presented with complex traumatic wounds. Thirty-one free
      flaps were performed for the 29 patients. Location of tissue defects included the
      lower extremity (15), face/neck (8), upper extremity (6). Limb salvage was
      successful in all but one patient. Six of eight patients with head and neck
      wounds were tolerating oral intake at the time of discharge. There were three
      flap losses in 3 patients; two patients who experienced flap loss underwent a
      successful second free or regional flap. Minor complications occurred in six
      patients. CONCLUSION: Microvascular free tissue transfer for complex tissue
      defects in a combat zone is a critically important task and can improve quality
      of life for host-nation patients. Major US combat hospitals deployed to a war
      zone should include personnel who are trained and capable of performing these
      complex reconstructive procedures and who understand the many nuances of
      optimizing outcomes in this challenging environment.

PMID- 23883912
TI  - Implementation of a military-derived damage-control resuscitation strategy in a
      civilian trauma center decreases acute hypoxia in massively transfused patients.
AB  - BACKGROUND: Recent military experience supports a paradigm shift in shock
      resuscitation to damage-control resuscitation (DCR), which emphasizes a plasma
      rich and crystalloid-poor approach to resuscitation. The effect of DCR on hypoxia
      after massive transfusion is unknown. We hypothesized that implementation of a
      military-derived DCR strategy in a civilian setting would lead to decreased acute
      hypoxia. METHODS: A DCR strategy was implemented in 2007. We retrospectively
      reviewed patients receiving trauma surgeon operative intervention and 10 or more
      units of packed red blood cells (pRBCs) within 24 hours of injury at an adult
      Level I trauma center from 2001 to 2010. Demographic data, blood requirements,
      and PaO2/FIO2 ratios were analyzed. To evaluate evolving resuscitation
      strategies, we fit linear trend models to continuous variables and tested their
      slopes for statistical significance. RESULTS: Two hundred sixteen patients met
      the study criteria, with a mean age of 35 +/- 1.1 years and Injury Severity Score
      (ISS) of 31 +/- 9.0. Of the patients, 80% were male, and 52% sustained
      penetrating injuries. Overall mortality was 32%. Overall mean pRBC and fresh
      frozen plasma (FFP) units infused in 24 hours were 23.2 +/- 1.1 and 18.6 +/- 1.1,
      respectively. Trends for patient age, sex, mechanism of injury, ISS, highest
      positive end-expiratory pressure, and mean total pRBC transfused over 24 hours
      were not statistically different from zero. An increasing trend in FFP and
      platelets transfused during the first 24 hours (p < 0.0001, p = 0.04,
      respectively) and a decrease in the pRBC/FFP ratio (p < 0.0001) were found. The
      amount of crystalloid infused during the initial 24 hours decreased with time (p
      < 0.0001). The lowest PaO2/FIO2 ratio recorded during the initial 24 hours
      increased during the study period (p = 0.01), indicating a statistically
      significant reduction in hypoxia. CONCLUSION: A military-derived DCR strategy can
      be implemented in the civilian setting. DCR led to significant increases in FFP
      transfusion, decreases in crystalloid use, and acute hypoxia.

PMID- 23883914
TI  - Use and complications of operative control of arterial inflow in combat
      casualties with traumatic lower-extremity amputations caused by improvised
      explosive devices.
AB  - BACKGROUND: Proximal traumatic lower-extremity amputation has become the
      signature injury of the war in Afghanistan. Casualties present in extremis and
      often require immediate operative control of arterial inflow to prevent
      exsanguination. This study evaluated the use of this strategy and its
      complications. METHODS: This is a retrospective analysis of case notes of UK
      service personnel, identified from the UK Joint Theatre Trauma Registry, who
      sustained traumatic lower-extremity amputation requiring suprainguinal vascular
      control, following improvised explosive device injury in Afghanistan, between
      July 2008 and December 2010. RESULTS: Fifty-one casualties were identified with a
      median Injury Severity Score (ISS) of 30. In 10 casualties, control was obtained
      via an extraperitoneal approach, and in 41, control was obtained via midline
      laparotomy and intraperitoneal (IP) approach. The most commonly controlled vessel
      in extraperitoneal control was the external iliac artery, and in IP control, the
      common iliac artery. Within the 41 patients who had IP control, 13 also required
      a therapeutic laparotomy, and 9 patients had bilateral injuries at the level of
      the proximal femur or higher. One patient, who had undergone IP control,
      experienced an injury to the common iliac vein, which was repaired. There were no
      other immediate complications recorded, and 39 casualties survived to discharge.
      CONCLUSION: This is the first study to characterize the methods of proximal
      control in high wartime lower-extremity amputees. Although some casualties will
      have abdominal injuries that necessitate laparotomy, the majority in our study
      did not; however, in the critically ill casualty, rapid proximal control is
      required. Novel methods of temporary hemorrhage control may reduce the need for,
      and burden of, cavity surgery. LEVEL OF EVIDENCE: Epidemiologic study, level III;
      prognostic study, level IV.

PMID- 23883915
TI  - Transfusion strategies and development of acute respiratory distress syndrome in
      combat casualty care.
AB  - BACKGROUND: Damage-control resuscitation (DCR) has been advocated to reduce
      mortality in military and civilian settings. However, DCR and excessive
      crystalloid resuscitation may be associated with a higher incidence of acute
      respiratory distress syndrome (ARDS). We sought to examine the impact of
      resuscitation strategies on ARDS development in combat casualty care. METHODS: A
      retrospective review of Joint Theater Trauma Registry data on US combat
      casualties who received at least 1 U of blood product within the first 24 hours
      of care was performed, cross-referenced with the cohort receiving mechanical
      ventilation (n = 1,475). Massive transfusion (MT, >=10 red blood cells [RBCs]
      and/or whole blood in 24 hours) and volume/ratios of plasma/RBC, platelet/RBC,
      and crystalloid/RBC (C/RBC, crystalloid liters/RBC units) were examined using
      bivariate/multivariate logistic regression and local regression analyses as ARDS
      risk factors, controlling for age, injury severity, admission systolic blood
      pressure, and Glasgow Coma Scale (GCS) score. RESULTS: ARDS was identified in 95
      cases (6.4%). MT was required in 550 (37.3%) of the analysis cohort. ARDS was
      more common in MT (46 of 550, 8.4%) versus no-MT cohort (49 of 925, 5.3%), but
      mortality was not different (17.4% MT vs. 16.3% no-MT). ARDS patients received
      significantly increased crystalloid of blood product volumes. Increased
      crystalloid resuscitation (C/RBC ratio > 1.5) occurred in 479 (32.7%) of 1,464
      patients. Unadjusted mortality was significantly increased in the cohort with
      C/RBC ratio of 1.5 or less compared with those with greater than 1.5 (19.1% vs.
      6.3%, p < 0.0001), but no difference in ARDS (6.5% vs. 6.6%) was identified.
      Platelet/RBC ratio did not impact on ARDS. Increasing plasma (odds ratio, 1.07; p
      = 0.0062) and crystalloid (odds ratio, 1.04; p = 0.041) volumes were confirmed as
      independent ARDS risk factors. CONCLUSION: In modern combat casualty care,
      increased plasma and crystalloid infusion were identified as independent risk
      factors for ARDS. These findings support a practice of decreased
      plasma/crystalloid transfusion in trauma resuscitation once hemorrhage control is
      established to achieve the mortality benefit of DCR and ARDS prevention.

PMID- 23883916
TI  - A comparison of health outcomes for combat amputee and limb salvage patients
      injured in Iraq and Afghanistan wars.
AB  - BACKGROUND: Treatment of military combatants who sustain leg-threatening injuries
      remains one of the leading challenges for military providers. The present study
      provides systematic health outcome data to inform decisions on the definitive
      surgical treatment, namely amputation versus limb salvage, for the most serious
      leg injuries. METHODS: This was a retrospective analysis of health records for
      patients who sustained serious lower-extremity injuries in the Iraq and
      Afghanistan conflicts, 2001 to 2008. Patients had (1) amputation during the first
      90 days after injury (early amputees, n = 587), (2) amputation more than 90 days
      after injury (late amputees, n = 84), or (3) leg-threatening injuries without
      amputation (limb salvage [LS], n = 117). Injury data and health outcomes were
      followed up to 24 months. RESULTS: After adjusting for group differences, early
      amputees and LS patients had similar rates for most physical complications. Early
      amputees had significantly reduced rates of psychological diagnoses
      (posttraumatic stress disorder, substance abuse) and received more outpatient
      care, particularly psychological, compared with LS patients. Late amputees had
      significantly higher rates of many mental and physical health diagnoses,
      including prolonged infections and pain issues, compared with early amputees or
      LS patients. CONCLUSION: Early amputation was associated with reduced rates of
      adverse health outcomes relative to late amputation or LS in the short term. Most
      evident was that late amputees had the poorest physical and psychological
      outcomes. These findings can inform health care providers of the differing
      clinical consequences of early amputation and LS. These results indicate the need
      for separate health care pathways for early and late amputees and LS patients.

PMID- 23883917
TI  - Cause and timing of death in massively transfused trauma patients.
AB  - BACKGROUND: The purpose of this study was to characterize the cause of death in
      severely injured trauma patients to define potential responses to resuscitation.
      METHODS: Prospective analysis of 190 critically injured patients who underwent
      massive transfusion protocol (MTP) activation or received massive transfusion
      (>10 U of packed red blood cells [RBC] per 24 hours). Cause of death was
      adjudicated into one of four categories as follows: (1) exsanguination, (2) early
      physiologic collapse, (3) late physiologic collapse, and (4) nonsurvivable
      injury. RESULTS: A total 190 patients underwent massive transfusion or MTP with
      76 deaths (40% mortality), of whom 72 deaths were adjudicated to one of four
      categories: 33.3% died of exsanguination, 16.6% died of early physiologic
      collapse, 11.1% died of late physiologic collapse, while 38.8% died of
      nonsurvivable injuries. Patients who died of exsanguination were younger and had
      the highest RBC/fresh frozen plasma ratio (2.97 [2.24]), although the early
      physiologic collapse group survived long enough to use the most blood products (p
      < 0.001). The late physiologic collapse group had significantly fewer penetrating
      injuries, was older, and had significantly more crystalloid use but received a
      lower RBC/fresh frozen plasma ratio (1.50 [0.42]). Those who were determined to
      have a nonsurvivable injury had a lower presenting Glasgow Coma Scale (GCS)
      score, fewer penetrating injuries, and higher initial blood pressure reflecting a
      preponderance of nonsurvivable traumatic brain injury. The average survival time
      for patients with potentially survivable injuries was 2.4 hours versus 18.4 hours
      for nonsurvivable injuries (p < 0.001). CONCLUSION: Severely injured patients
      requiring MTP have a high mortality rate. However, no studies to date have
      addressed the cause of death after MTP. Characterization of cause of death will
      allow targeting of surgical and resuscitative conduct to allow extension of the
      physiologic reserve time, therefore rendering previously nonsurvivable injury
      potentially survivable.

PMID- 23883918
TI  - Injury pattern and mortality of noncompressible torso hemorrhage in UK combat
      casualties.
AB  - BACKGROUND: Hemorrhage following traumatic injury is a leading cause of military
      and civilian mortality. Noncompressible torso hemorrhage (NCTH) has been
      identified as particularly lethal, especially in the prehospital setting.
      METHODS: All patients sustaining NCTH between August 2002 and July 2012 were
      identified from the UK Joint Theatre Trauma Registry. NCTH was defined as injury
      to a named torso axial vessel, pulmonary injury, solid-organ injury (Grade 4 or
      greater injury to the liver, kidney, or spleen) or pelvic fracture with ring
      disruption. Patients with ongoing hemorrhage were identified using either a
      systolic blood pressure of less than 90 mm Hg or the need for immediate surgical
      hemorrhage control. Data on injury pattern and location as well as cause of death
      were analyzed using univariate and multivariate analyses. RESULTS: During 10
      years, 296 patients were identified with NCTH, with a mortality of 85.5%. The
      majority of deaths occurred before hospital admission (n = 222, 75.0%). Of
      patients admitted to hospital, survivors (n = 43, 14.5%) had a higher median
      systolic blood pressure (108 [43] vs. 89 [46], p = 0.123) and Glasgow Coma Scale
      (GCS) (14 [12] vs. 3 [0], p < 0.001) compared with in-hospital deaths (n = 31,
      10.5%). Hemorrhage was the more common cause of death (60.1%), followed by
      central nervous system disruption (30.8%), total body disruption (5.1%), and
      multiple-organ failure (4.0%). On multivariate analysis, major arterial and
      pulmonary hilar injury are most lethal with odds ratio (95% confidence interval)
      of 16.44 (5.50-49.11) and 9.61 (1.06-87.00), respectively. CONCLUSION: This study
      demonstrates that the majority of patients sustaining NCTH die before hospital
      admission, with exsanguination and central nervous system disruption contributing
      to the bulk cause of death. Major arterial and pulmonary hilar injuries are
      independent predictors of mortality.

PMID- 23883919
TI  - Primary blast lung injury prevalence and fatal injuries from explosions: insights
      from postmortem computed tomographic analysis of 121 improvised explosive device
      fatalities.
AB  - BACKGROUND: Primary blast lung injury (PBLI) is an acknowledged cause of death in
      explosive blast casualties. In contrast to vehicle occupants following an in
      vehicle explosion, the injury profile, including PBLI incidence, for mounted
      personnel following an external explosion has yet to be as well defined. METHODS:
      This retrospective study identified 146 cases of UK military personnel killed by
      improvised explosive devices (IEDs) between November 2007 and July 2010. With the
      permission of Her Majesty's Coroners, relevant postmortem computed tomography
      imaging was analyzed. PBLI was diagnosed by postmortem computed tomography.
      Injury, demographic, and relevant incident data were collected via the UK Joint
      Theatre Trauma Registry. RESULTS: Autopsy results were not available for 1 of 146
      cases. Of the remaining 145 IED fatalities, 24 had catastrophic injuries
      (disruptions), making further study impossible, leaving 121 cases; 79 were
      dismounted (DM), and 42 were mounted (M). PBLI was noted in 58 cases, 33 (79%) of
      42 M fatalities and 25 (32%) of 79 DM fatalities (p < 0.0001). Rates of
      associated thoracic trauma were also significantly greater in the M group (p <
      0.006 for all). Fatal head (53% vs. 23%) and thoracic trauma (23% vs. 8%) were
      both more common in the M group, while fatal lower extremity trauma (7% vs. 48%)
      was more commonly seen in DM casualties (p < 0.0001 for all). CONCLUSION:
      Following IED strikes, mounted fatalities are primarily caused by head and chest
      injuries. Lower extremity trauma is the leading cause of death in dismounted
      fatalities. Mounted fatalities have a high incidence of PBLI, suggesting
      significant exposure to primary blast. This has not been reported previously.
      Further work is required to determine the incidence and clinical significance of
      this severe lung injury in explosive blast survivors. In addition, specific
      characteristics of the vehicles should be considered.

PMID- 23883920
TI  - Developability studies before initiation of process development: improving
      manufacturability of monoclonal antibodies.
AB  - Monoclonal antibodies constitute a robust class of therapeutic proteins. Their
      stability, resistance to stress conditions and high solubility have allowed the
      successful development and commercialization of over 40 antibody-based drugs.
      Although mAbs enjoy a relatively high probability of success compared with other
      therapeutic proteins, examples of projects that are suspended due to the
      instability of the molecule are not uncommon. Developability assessment studies
      have therefore been devised to identify early during process development problems
      associated with stability, solubility that is insufficient to meet expected
      dosing or sensitivity to stress. This set of experiments includes short-term
      stability studies at 2-8 pC, 25 pC and 40 pC, freeze-thaw studies, limited forced
      degradation studies and determination of the viscosity of high concentration
      samples. We present here three case studies reflecting three typical outcomes:
      (1) no major or unexpected degradation is found and the study results are used to
      inform early identification of degradation pathways and potential critical
      quality attributes within the Quality by Design framework defined by US Food and
      Drug Administration guidance documents; (2) identification of specific
      degradation pathway(s) that do not affect potency of the molecule, with
      subsequent definition of proper process control and formulation strategies; and
      (3) identification of degradation that affects potency, resulting in program
      termination and reallocation of resources. 

PMID- 23883921
TI  - Chromatographic analysis of methylglyoxal and other alpha-dicarbonyls using gas
      diffusion microextraction.
AB  - Many alpha-dicarbonyl compounds such as methylglyoxal, diacetyl and pentane-2,3
      dione are important quality markers of processed foods. They are produced by
      enzymatic and chemical processes, the Maillard reaction is the most known
      chemical route for alpha-dicarbonyl formation. In the case of methylglyoxal,
      there are obstacles to be overcome when analysing this compound due to its high
      reactivity, low volatility and low concentration. The use of extraction
      techniques based on the volatilization of methylglyoxal (like solid-phase
      microextraction) showed to be ineffective for the methylglyoxal extraction from
      aqueous solutions. Therefore, derivatization is typically applied to increase
      analyte's volatility. In this work a new methodology for the extraction and
      analysis of methylglyoxal and also diacetyl and pentane-2,3-dione from selected
      food matrices is presented. It is based on a gas-diffusion microextraction step
      followed by high performance liquid chromatographic analysis. It was successfully
      applied to port wines, black tea and soy sauce. Methylglyoxal, diacetyl and
      pentane-2,3-dione were quantified in the following concentration ranges: 0.24
      1.74 mg L(-1), 0.1-1.85 mg L(-1) and 0.023-0.15 mg L(-1), respectively. The main
      advantages over existing methodologies are its simplicity in terms of sample
      handling, not requiring any chemical modification of the alpha-dicarbonyls prior
      to the extraction, low reagent consumption and short time of analysis. 

PMID- 23883923
TI  - EGFR inhibitors for wild-type EGFR NSCLC: to use or not to use?

PMID- 23883924
TI  - Alzheimer's disease: From big data to mechanism.

PMID- 23883922
TI  - Erlotinib versus docetaxel as second-line treatment of patients with advanced non
      small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised
      controlled trial.
AB  - BACKGROUND: Erlotinib is registered for treatment of all patients with advanced
      non-small-cell lung cancer (NSCLC). However, its efficacy for treatment of
      patients whose tumours are EGFR wild-type-which includes most patients-is still
      contentious. We assessed the efficacy of erlotinib compared with a standard
      second-line chemotherapy in such patients. METHODS: We did this randomised
      controlled trial in 52 Italian hospitals. We enrolled patients who had metastatic
      NSCLC, had had platinum-based chemotherapy, and had wild-type EGFR as assessed by
      direct sequencing. Patients were randomly assigned centrally (1:1) to receive
      either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m(2) every 21
      days or 35 mg/m(2) on days 1, 8, and 15, every 28 days. Randomisation was
      stratified by centre, stage, type of first-line chemotherapy, and performance
      status. Patients and investigators who gave treatments or assessed outcomes were
      not masked to treatment allocation, investigators who analysed results were. The
      primary endpoint was overall survival in the intention-to-treat population. The
      study is registered at ClinicalTrials.gov, number NCT00637910. FINDINGS: We
      screened 702 patients, of whom we genotyped 540. 222 patients were enrolled (110
      assigned to docetaxel vs 112 assigned to erlotinib). Median overall survival was
      8.2 months (95% CI 5.8-10.9) with docetaxel versus 5.4 months (4.5-6.8) with
      erlotinib (adjusted hazard ratio [HR] 0.73, 95% CI 0.53-1.00; p=0.05).
      Progression-free survival was significantly better with docetaxel than with
      erlotinib: median progression-free survival was 2.9 months (95% CI 2.4-3.8) with
      docetaxel versus 2.4 months (2.1-2.6) with erlotinib (adjusted HR 0.71, 95% CI
      0.53-0.95; p=0.02). The most common grade 3-4 toxic effects were: low absolute
      neutrophil count (21 [20%] of 104 in the docetaxel group vs none of 107 in the
      erlotinib group), skin toxic effects (none vs 15 [14%]), and asthenia (ten [10%]
      vs six [6%]). INTERPRETATION: Our results show that chemotherapy is more
      effective than erlotinib for second-line treatment for previously treated
      patients with NSCLC who have wild-type EGFR tumours.

PMID- 23883925
TI  - Regenerative biology: On with their heads.

PMID- 23883926
TI  - Climate science: Unequal equinoxes.

PMID- 23883927
TI  - Oil palm genome sequence reveals divergence of interfertile species in Old and
      New worlds.
AB  - Oil palm is the most productive oil-bearing crop. Although it is planted on only
      5% of the total world vegetable oil acreage, palm oil accounts for 33% of
      vegetable oil and 45% of edible oil worldwide, but increased cultivation competes
      with dwindling rainforest reserves. We report the 1.8-gigabase (Gb) genome
      sequence of the African oil palm Elaeis guineensis, the predominant source of
      worldwide oil production. A total of 1.535 Gb of assembled sequence and
      transcriptome data from 30 tissue types were used to predict at least 34,802
      genes, including oil biosynthesis genes and homologues of WRINKLED1 (WRI1), and
      other transcriptional regulators, which are highly expressed in the kernel. We
      also report the draft sequence of the South American oil palm Elaeis oleifera,
      which has the same number of chromosomes (2n = 32) and produces fertile
      interspecific hybrids with E. guineensis but seems to have diverged in the New
      World. Segmental duplications of chromosome arms define the palaeotetraploid
      origin of palm trees. The oil palm sequence enables the discovery of genes for
      important traits as well as somaclonal epigenetic alterations that restrict the
      use of clones in commercial plantings, and should therefore help to achieve
      sustainability for biofuels and edible oils, reducing the rainforest footprint of
      this tropical plantation crop. 

PMID- 23883928
TI  - The molecular logic for planarian regeneration along the anterior-posterior axis.
AB  - The planarian Dugesia japonica can regenerate a complete individual from a head,
      trunk or tail fragment via activation of somatic pluripotent stem cells. About a
      century ago, Thomas Hunt Morgan attempted to explain the extraordinary
      regenerative ability of planarians by positing two opposing morphogenetic
      gradients of formative "head stuff" and "tail stuff" along the anterior-posterior
      axis. However, Morgan's hypothesis remains open to debate. Here we show that
      extracellular signal-related kinase (ERK) and Wnt/beta-catenin signalling
      pathways establish a solid framework for planarian regeneration. Our data suggest
      that ERK signalling forms a spatial gradient in the anterior region during
      regeneration. The fibroblast growth factor receptor-like gene nou-darake (which
      serves as an output of ERK signalling in the differentiating head) and
      posteriorly biased beta-catenin activity negatively regulate ERK signalling along
      the anterior-posterior axis in distinct manners, and thereby posteriorize
      regenerating tissues outside the head region to reconstruct a complete head-to
      tail axis. On the basis of this knowledge about D. japonica, we proposed that
      beta-catenin signalling is responsible for the lack of head-regenerative ability
      of tail fragments in the planarian Phagocata kawakatsui, and our confirmation
      thereof supports the notion that posterior beta-catenin signalling negatively
      modulates the ERK signalling involved in anteriorization across planarian
      species. These findings suggest that ERK signalling has a pivotal role in
      triggering globally dynamic differentiation of stem cells in a head-to-tail
      sequence through a default program that promotes head tissue specification in the
      absence of posteriorizing signals. Thus, we have confirmed the broad outline of
      Morgan's hypothesis, and refined it on the basis of our proposed default property
      of planarian stem cells. 

PMID- 23883929
TI  - Restoration of anterior regeneration in a planarian with limited regenerative
      ability.
AB  - Variability of regenerative potential among animals has long perplexed
      biologists. On the basis of their exceptional regenerative abilities, planarians
      have become important models for understanding the molecular basis of
      regeneration. However, planarian species with limited regenerative abilities are
      also found. Despite the importance of understanding the differences between
      closely related, regenerating and non-regenerating organisms, few studies have
      focused on the evolutionary loss of regeneration, and the molecular mechanisms
      leading to such regenerative loss remain obscure. Here we examine Procotyla
      fluviatilis, a planarian with restricted ability to replace missing tissues,
      using next-generation sequencing to define the gene expression programs active in
      regeneration-permissive and regeneration-deficient tissues. We found that Wnt
      signalling is aberrantly activated in regeneration-deficient tissues. Notably,
      downregulation of canonical Wnt signalling in regeneration-deficient regions
      restores regenerative abilities: blastemas form and new heads regenerate in
      tissues that normally never regenerate. This work reveals that manipulating a
      single signalling pathway can reverse the evolutionary loss of regenerative
      potential. 

PMID- 23883931
TI  - Cancer: Angiogenic awakening.

PMID- 23883930
TI  - The oil palm SHELL gene controls oil yield and encodes a homologue of SEEDSTICK.
AB  - A key event in the domestication and breeding of the oil palm Elaeis guineensis
      was loss of the thick coconut-like shell surrounding the kernel. Modern E.
      guineensis has three fruit forms, dura (thick-shelled), pisifera (shell-less) and
      tenera (thin-shelled), a hybrid between dura and pisifera. The pisifera palm is
      usually female-sterile. The tenera palm yields far more oil than dura, and is the
      basis for commercial palm oil production in all of southeast Asia. Here we
      describe the mapping and identification of the SHELL gene responsible for the
      different fruit forms. Using homozygosity mapping by sequencing, we found two
      independent mutations in the DNA-binding domain of a homologue of the MADS-box
      gene SEEDSTICK (STK, also known as AGAMOUS-LIKE 11), which controls ovule
      identity and seed development in Arabidopsis. The SHELL gene is responsible for
      the tenera phenotype in both cultivated and wild palms from sub-Saharan Africa,
      and our findings provide a genetic explanation for the single gene hybrid vigour
      (or heterosis) attributed to SHELL, via heterodimerization. This gene mutation
      explains the single most important economic trait in oil palm, and has
      implications for the competing interests of global edible oil production,
      biofuels and rainforest conservation. 

PMID- 23883932
TI  - Reactivating head regrowth in a regeneration-deficient planarian species.
AB  - Species capable of regenerating lost body parts occur throughout the animal
      kingdom, yet close relatives are often regeneration incompetent. Why in the face
      of 'survival of the fittest' some animals regenerate but others do not remains a
      fascinating question. Planarian flatworms are well known and studied for their
      ability to regenerate from minute tissue pieces, yet species with limited
      regeneration abilities have been described even amongst planarians. Here we
      report the characterization of the regeneration defect in the planarian
      Dendrocoelum lacteum and its successful rescue. Tissue fragments cut from the
      posterior half of the body of this species are unable to regenerate a head and
      ultimately die. We find that this defect originates during the early stages of
      head specification, which require inhibition of canonical Wnt signalling in other
      planarian species. Notably, RNA interference (RNAi)-mediated knockdown of Dlac
      beta-catenin-1, the Wnt signal transducer, restored the regeneration of fully
      functional heads on tail pieces, rescuing D. lacteum's regeneration defect. Our
      results demonstrate the utility of comparative studies towards the reactivation
      of regenerative abilities in regeneration-deficient animals. Furthermore, the
      availability of D. lacteum as a regeneration-impaired planarian model species
      provides a first step towards elucidating the evolutionary mechanisms that
      ultimately determine why some animals regenerate and others do not. 

PMID- 23883934
TI  - Seasonal sea surface cooling in the equatorial Pacific cold tongue controlled by
      ocean mixing.
AB  - Sea surface temperature (SST) is a critical control on the atmosphere, and
      numerical models of atmosphere-ocean circulation emphasize its accurate
      prediction. Yet many models demonstrate large, systematic biases in simulated SST
      in the equatorial 'cold tongues' (expansive regions of net heat uptake from the
      atmosphere) of the Atlantic and Pacific oceans, particularly with regard to a
      central but little-understood feature of tropical oceans: a strong seasonal
      cycle. The biases may be related to the inability of models to constrain
      turbulent mixing realistically, given that turbulent mixing, combined with
      seasonal variations in atmospheric heating, determines SST. In temperate oceans,
      the seasonal SST cycle is clearly related to varying solar heating; in the
      tropics, however, SSTs vary seasonally in the absence of similar variations in
      solar inputs. Turbulent mixing has long been a likely explanation, but firm, long
      term observational evidence has been absent. Here we show the existence of a
      distinctive seasonal cycle of subsurface cooling via mixing in the equatorial
      Pacific cold tongue, using multi-year measurements of turbulence in the ocean. In
      boreal spring, SST rises by 2 kelvin when heating of the upper ocean by the
      atmosphere exceeds cooling by mixing from below. In boreal summer, SST decreases
      because cooling from below exceeds heating from above. When the effects of
      lateral advection are considered, the magnitude of summer cooling via mixing (4
      kelvin per month) is equivalent to that required to counter the heating terms.
      These results provide quantitative assessment of how mixing varies on timescales
      longer than a few weeks, clearly showing its controlling influence on seasonal
      cooling of SST in a critical oceanic regime. 

PMID- 23883933
TI  - The pluripotent genome in three dimensions is shaped around pluripotency factors.
AB  - It is becoming increasingly clear that the shape of the genome importantly
      influences transcription regulation. Pluripotent stem cells such as embryonic
      stem cells were recently shown to organize their chromosomes into topological
      domains that are largely invariant between cell types. Here we combine chromatin
      conformation capture technologies with chromatin factor binding data to
      demonstrate that inactive chromatin is unusually disorganized in pluripotent stem
      cell nuclei. We show that gene promoters engage in contacts between topological
      domains in a largely tissue-independent manner, whereas enhancers have a more
      tissue-restricted interaction profile. Notably, genomic clusters of pluripotency
      factor binding sites find each other very efficiently, in a manner that is
      strictly pluripotent-stem-cell-specific, dependent on the presence of Oct4 and
      Nanog protein and inducible after artificial recruitment of Nanog to a selected
      chromosomal site. We conclude that pluripotent stem cells have a unique higher
      order genome structure shaped by pluripotency factors. We speculate that this
      interactome enhances the robustness of the pluripotent state. 

PMID- 23883935
TI  - No increase in global temperature variability despite changing regional patterns.
AB  - Evidence from Greenland ice cores shows that year-to-year temperature variability
      was probably higher in some past cold periods, but there is considerable interest
      in determining whether global warming is increasing climate variability at
      present. This interest is motivated by an understanding that increased
      variability and resulting extreme weather conditions may be more difficult for
      society to adapt to than altered mean conditions. So far, however, in spite of
      suggestions of increased variability, there is considerable uncertainty as to
      whether it is occurring. Here we show that although fluctuations in annual
      temperature have indeed shown substantial geographical variation over the past
      few decades, the time-evolving standard deviation of globally averaged
      temperature anomalies has been stable. A feature of the changes has been a
      tendency for many regions of low variability to experience increases, which might
      contribute to the perception of increased climate volatility. The normalization
      of temperature anomalies creates the impression of larger relative overall
      increases, but our use of absolute values, which we argue is a more appropriate
      approach, reveals little change. Regionally, greater year-to-year changes
      recently occurred in much of North America and Europe. Many climate models
      predict that total variability will ultimately decrease under high greenhouse gas
      concentrations, possibly associated with reductions in sea-ice cover. Our
      findings contradict the view that a warming world will automatically be one of
      more overall climatic variation. 

PMID- 23883937
TI  - CAMbrella--complementary medicine research in Europe.

PMID- 23883938
TI  - CAMbrella--a pan-European research network for complementary and alternative
      medicine: from the beginnings up to first results.

PMID- 23883936
TI  - Integrative genomics identifies APOE epsilon4 effectors in Alzheimer's disease.
AB  - Late-onset Alzheimer's disease (LOAD) risk is strongly influenced by genetic
      factors such as the presence of the apolipoprotein E epsilon4 allele (referred to
      here as APOE4), as well as non-genetic determinants including ageing. To pursue
      mechanisms by which these affect human brain physiology and modify LOAD risk, we
      initially analysed whole-transcriptome cerebral cortex gene expression data in
      unaffected APOE4 carriers and LOAD patients. APOE4 carrier status was associated
      with a consistent transcriptomic shift that broadly resembled the LOAD profile.
      Differential co-expression correlation network analysis of the APOE4 and LOAD
      transcriptomic changes identified a set of candidate core regulatory mediators.
      Several of these--including APBA2, FYN, RNF219 and SV2A--encode known or novel
      modulators of LOAD associated amyloid beta A4 precursor protein (APP) endocytosis
      and metabolism. Furthermore, a genetic variant within RNF219 was found to affect
      amyloid deposition in human brain and LOAD age-of-onset. These data implicate an
      APOE4 associated molecular pathway that promotes LOAD.

PMID- 23883939
TI  - Towards a pan-European definition of complementary and alternative medicine--a
      realistic ambition?
AB  - BACKGROUND: The terms used for defining complementary and alternative medicine
      (CAM) including the methods, procedures and therapies vary greatly. The task of
      the CAMbrella working group on terminology was to explore the existing CAM
      terminologies and to develop a pragmatic definition of CAM that is acceptable
      Europe-wide. This can then be used to systematically research, e.g., its
      prevalence and legal status and to investigate the citizens' demands on CAM and
      the perspectives of providers of CAM in Europe. METHODS: Terms and definitions
      were collected from both scientific and non-scientific sources. The terms and
      definitions identified were analysed and discussed among the CAMbrella working
      group participants on several occasions with the aim of arriving at a consensus.
      RESULTS: We developed a proposal for a pragmatic European definition of CAM:
      'Complementary and alternative medicine (CAM) utilised by European citizens
      represents a variety of different medical systems and therapies based on the
      knowledge, skills and practices derived from theories, philosophies and
      experiences used to maintain and improve health, as well as to prevent, diagnose,
      relieve or treat physical and mental illnesses. CAM has been mainly used outside
      conventional health care, but in some countries certain treatments are being
      adopted or adapted by conventional health care.' CONCLUSION: Developing a
      uniform, pragmatic pan-European definition of CAM was complicated by a number of
      factors. These included the vast diversity of existing definitions, systems,
      disciplines, procedures, methods and therapies available within the EU.

PMID- 23883940
TI  - What attitudes and needs do citizens in Europe have in relation to complementary
      and alternative medicine?
AB  - BACKGROUND: Surveys from several European countries suggest a European-wide
      increase in the use of Complementary and Alternative Medicine (CAM). To safeguard
      citizens' rights concerning their healthcare, it is critical to gain an overview
      of citizens' attitudes and to understand their expectations and needs regarding
      CAM. METHODS: A review of literature was undertaken, based on systematic searches
      of the following electronic databases: PubMed, Web of Science, CINHAL, AMED,
      PsycINFO and PsycArticles; 189 articles met inclusion criteria. Articles were
      analysed thematically and their reporting quality assessed. RESULTS: Despite the
      limited availability of research-based knowledge about citizens' attitudes and
      needs concerning CAM in many European countries, some trends can be noted. Many
      citizens hold positive attitudes to CAM and wish for increasing access to CAM
      provision. Citizens call for impartial, reliable and trustworthy information to
      support informed decision-making, and some citizens wish for greater support and
      involvement of biomedical healthcare professionals in facilitating their
      healthcare choices. While citizens value distinct aspects of CAM practice, they
      are also critical consumers and support clear regulatory and educational
      frameworks to ensure the quality and safety of CAM provision and medicinal
      products. CONCLUSION: To gain knowledge on citizens' needs and attitudes to CAM
      across Europe further research is required on 3 main issues: i) how citizens
      across Europe obtain information about CAM and the needs they may have for
      trustworthy information sources, ii) the local situations for accessing CAM and
      iii) citizens' perspectives on the quality of care and safety of CAM provision
      and products.

PMID- 23883941
TI  - A systematic literature review of complementary and alternative medicine
      prevalence in EU.
AB  - BACKGROUND: Studies suggest that complementary and alternative medicine (CAM) is
      widely used in the European Union (EU). We systematically reviewed data,
      reporting research quality and the prevalence of CAM use by citizens in Europe;
      what it is used for, and why. METHODS: We searched for general population surveys
      of CAM use by using Ovid MEDLINE (1948 to September 2010), Cochrane Library (1989
      to September 2010), CINAHL (1989 to September 2010), EMBASE (1980 to September
      2010), PsychINFO including PsychARTICLES (1989 to September 2010), Web of Science
      (1989 to September 2010), AMED (1985 to September 2010), and CISCOM (1989 to
      September 2010). Additional studies were identified through experts and grey
      literature. Cross-sectional, population-based or cohort studies reporting CAM use
      in any EU language were included. Data were extracted and reviewed by 2 authors
      using a pre-designed extraction protocol with quality assessment instrument.
      RESULTS: 87 studies were included. Inter-rater reliability was good (kappa =
      0.8). Study methodology and quality of reporting were poor. The prevalence of CAM
      use varied widely within and across EU countries (0.3-86%). Prevalence data
      demonstrated substantial heterogeneity unrelated to report quality; therefore, we
      were unable to pool data for meta-analysis; our report is narrative and based on
      descriptive statistics. Herbal medicine was most commonly reported. CAM users
      were mainly women. The most common reason for use was dissatisfaction with
      conventional care; CAM was widely used for musculoskeletal problems. CONCLUSION:
      CAM prevalence across the EU is problematic to estimate because studies are
      generally poor and heterogeneous. A consistent definition of CAM, a core set of
      CAMs with country-specific variations and a standardised reporting strategy to
      enhance the accuracy of data pooling would improve reporting quality.

PMID- 23883942
TI  - Legal status and regulation of complementary and alternative medicine in Europe.
AB  - OBJECTIVE: The study aims to review the legal and regulatory status of
      complementary and alternative medicine (CAM) in the 27 European Union (EU) member
      states and 12 associated states, and at the EU/European Economic Association
      (EEA) level. METHODS: Contact was established with national Ministries of Health,
      Law or Education, members of national and European CAM associations, and
      CAMbrella partners. A literature search was performed in governmental and
      scientific/non-scientific websites as well as the EUROPA and EUR-lex websites/
      databases to identify documents describing national CAM regulation and official
      EU law documents. RESULTS: The 39 nations have all structured legislation and
      regulation differently: 17 have a general CAM legislation, 11 of these have a
      specific CAM law, and 6 have sections on CAM included in their general healthcare
      laws. Some countries only regulate specific CAM treatments. CAM medicinal
      products are subject to the same market authorization procedures as other
      medicinal products with the possible exception of documentation of efficacy. The
      directives, regulations and resolutions in the EU that may influence the
      professional practice of CAM will also affect the conditions under which patients
      are receiving CAM treatment(s) in Europe. CONCLUSION: There is an extraordinary
      diversity with regard to the regulation of CAM practice, but not CAM medicinal
      products. This will influence patients, practitioners and researchers when
      crossing European borders. Voluntary harmonization is possible within current
      legislation. Individual states within culturally similar regions should harmonize
      their CAM legislation and regulation. This can probably safeguard against
      inadequately justified over- or underregulation at the national level.

PMID- 23883943
TI  - Complementary and alternative medicine provision in Europe--first results
      approaching reality in an unclear field of practices.
AB  - BACKGROUND: The demand for complementary and alternative medicine (CAM) treatment
      in the European Union (EU) has led to an increase in the various CAM
      interventions available to the public. Our aim was to describe the CAM services
      available from both registered medical practitioners and registered non-medical
      practitioners. METHODS: Our literature search comprised a PubMed search of any
      scientific publications, secondary references and so-called grey literature, a
      search of government websites and websites of CAM organisations to collect data
      in a systematic manner, and personal communications, e.g., via e-mail contact.
      Due to the different reliability of data sources, a classification was developed
      and implemented. This weighted database was condensed into tables and maps to
      display the provision of CAM disciplines by country, showing the distribution of
      CAM providers across countries. RESULTS: Approximately 305,000 registered CAM
      providers can be identified in the EU (~160,000 non-medical and ~145,000 medical
      practitioners). Acupuncture (n = 96,380) is the most available therapeutic method
      for both medical (80,000) and non-medical (16,380) practitioners, followed by
      homeopathy (45,000 medical and 5,800 non-medical practitioners). Herbal medicine
      (29,000 practitioners) and reflexology (24,600 practitioners) are mainly provided
      by non-medical practitioners. Naturopathy (22,300) is dominated by 15,000 (mostly
      German) doctors. Anthroposophic medicine (4,500) and neural therapy (1,500) are
      practised by doctors only. CONCLUSION: CAM provision in the EU is maintained by
      approximately 305,000 registered medical doctors and non-medical practitioners,
      with a huge variability in its national regulatory management, which makes any
      direct comparison across the EU almost impossible. Harmonisation of legal status,
      teaching and certification of expertise for therapists would be of enormous value
      and should be developed.

PMID- 23883944
TI  - International development of traditional medicine / complementary and alternative
      medicine research--what can Europe learn?
AB  - BACKGROUND: The aim of this study was to analyse global research and development
      (R&D) strategies for traditional medicine (TM) and complementary and alternative
      medicine (CAM) across the world to learn from previous and on-going activities.
      METHODS: 52 representatives within CAMbrella nominated 43 key international
      stakeholders (individuals and organisations) and 15 of these were prioritised.
      Information from policy documents including mission statements, R&D strategies
      and R&D activities were collected in combination with personal interviews. Data
      were analysed using the principles of content analysis. RESULTS: Key stakeholders
      vary greatly in terms of capacity, mission and funding source (private/public).
      They ranged from only providing research funding to having a comprehensive R&D
      and communication agenda. A common shift in R&D strategy was noted; whereas 10
      years ago research focused mainly on exploring efficacy and mechanisms, today the
      majority of stakeholders emphasise the importance of a broad spectrum of
      research, including methodologies exploring context, safety and comparative
      effectiveness. CONCLUSION: The scarce public investment in this field in Europe
      stands in stark contrast to the large investments found in Australia, Asia and
      North America. There is an emerging global trend supporting a broad research
      repertoire, including qualitative and comparative effectiveness research. This
      trend should be considered by the EU given the experience and the substantial
      research funding committed by the included stakeholders. To facilitate
      international collaborative efforts and minimise the risk of investment failure,
      we recommend the formation of a centralised EU CAM research centre fostering a
      broad CAM R&D agenda with the responsibility for implementing the relevant
      findings of CAMbrella.

PMID- 23883945
TI  - Key issues in clinical and epidemiological research in complementary and
      alternative medicine--a systematic literature review.
AB  - BACKGROUND: In the last 2 decades there has been a large increase in publications
      on complementary and alternative medicine (CAM). However, CAM research
      methodology was heterogeneous and often of low quality. The aim of this
      systematic review was to investigate scientific publications with regards to
      general issues, concepts and strategies. We also looked at research priorities
      and methods employed to evaluate the clinical and epidemiological research of CAM
      in the past to identify the basis for consensus-based research strategies.
      METHODS: We performed a systematic literature search for papers published between
      1990 and 2010 in 7 electronic databases (Medline, Web of Science, PsychArticles,
      PsycInfo, CINAHL, EMBASE and Cochrane Library) on December 16 and 17, 2010. In
      addition, experts were asked to nominate relevant papers. Inclusion criteria were
      publications dealing with research methodology, priorities or complexities in the
      scientific evaluation of CAM. All references were assessed in a multistage
      process to identify relevant papers. RESULTS: From the 3,279 references derived
      from the search and 98 references contributed by CAM experts, 170 papers
      fulfilled the criteria and were included in the analysis. The following key
      issues were identified: difficulties in past CAM research (e.g., randomisation,
      blinding), utility of quantitative and qualitative research methods in CAM,
      priority setting in CAM research and specific issues regarding various CAM
      modalities. CONCLUSIONS: Most authors vote for the use of commonly accepted
      research methods to evaluate CAM. There was broad consensus that a mixed methods
      approach is the most suitable for gathering conclusive knowledge about CAM.

PMID- 23883946
TI  - Building a sustainable complementary and alternative medicine research network in
      Europe.
AB  - BACKGROUND: Since CAMbrella is a networking project funded by the European
      Commission explicitly to build and sustain a complementary and alternative
      medicine (CAM) research network in Europe, communication and dissemination play a
      large role and form a work package of their own. The present article gives an
      outline of the communication and dissemination work in the CAMbrella consortium.
      The intensive building of sound internal communication is an essential part in
      establishing a functioning structure for collaboration in a diverse group of 16
      partner institutions from 12 countries, as exists in the CAMbrella project.
      METHODS: The means and tools for dissemination of results to the scientific
      community and the European public at large, as well as to the European policy
      makers, are presented. The development of the corporate design and a
      dissemination strategy are described in detail. In addition, some basic
      information regarding previous CAM research efforts, which might be interesting
      for future consortium building in the field of CAM research, is given. RESULTS:
      Internal communication within a heterogeneous research group, the maintenance of
      a work-oriented style of communication and a consensus oriented effort in
      establishing dissemination tools and products will be essential for any future
      consortium in the CAM field. CONCLUSION: The outlook shows the necessity for
      active political encouragement of CAM research and the desideratum of a Pan
      European institution analogous to the NIH (National Institutes of Health) in the
      USA.

PMID- 23883947
TI  - Characteristics and survival of patients with invasive amelanotic melanoma in the
      USA.
AB  - Amelanotic melanoma (AM) has not been well characterized on a population-based
      level. Using cross-sectional, prospective data from 18 Surveillance,
      Epidemiology, and End Results registries, we carried out chi(2)-tests to compare
      characteristics of patients with AM with characteristics of patients with
      melanotic melanoma (MM), the Kaplan-Meier method to calculate 5-year survival
      among patients with AM and MM by stage, and competing risks regression to
      generate subdistribution hazard ratios for patients with AM using age, sex, and
      stage as predictors. We identified 628 cases of AM and 157,524 cases of MM.
      Patients with AM were more often male and older than patients with MM (P = 0.011
      and P < 0.001, respectively). AM was more common on the face/ears compared with
      MM and less common on the trunk (P = 0.004 and P < 0.001, respectively).
      Ulceration was over three times more common among patients with AM than among
      patients with MM (38.0 vs. 12.5%, P < 0.001), and it remained more common among
      patients with AM even when stratified by Breslow depths of up to 2 mm (P <
      0.001). Patients with AM were over three times more likely than patients with MM
      to have distant disease at diagnosis (10.0 vs. 2.9%, P < 0.001). Five-year
      melanoma-specific survival was significantly lower in patients with AM than in
      patients with MM (72.3 vs. 91.1%, P < 0.001). In competing risks regression, only
      stage was a significant predictor of melanoma-specific death. Our results
      demonstrate that the demographics of patients with AM and MM differ. AM is more
      advanced at diagnosis and is often more lethal than MM. Understanding the
      epidemiology of AM may help identify patients at highest risk and improve
      strategies for early detection.

PMID- 23883948
TI  - Isolation and chemical analysis of nanoparticles from English ivy (Hedera helix
      L.).
AB  - Bio-inspiration for novel adhesive development has drawn increasing interest in
      recent years with the discovery of the nanoscale morphology of the gecko footpad
      and mussel adhesive proteins. Similar to these animal systems, it was discovered
      that English ivy (Hedera helix L.) secretes a high strength adhesive containing
      uniform nanoparticles. Recent studies have demonstrated that the ivy
      nanoparticles not only contribute to the high strength of this adhesive, but also
      have ultraviolet (UV) protective abilities, making them ideal for sunscreen and
      cosmetic fillers, and may be used as nanocarriers for drug delivery. To make
      these applications a reality, the chemical nature of the ivy nanoparticles must
      be elucidated. In the current work, a method was developed to harvest bulk ivy
      nanoparticles from an adventitious root culture system, and the chemical
      composition of the nanoparticles was analysed. UV/visible spectroscopy,
      inductively coupled plasma mass spectrometry, Fourier transform infrared
      spectroscopy and electrophoresis were used in this study to identify the chemical
      nature of the ivy nanoparticles. Based on this analysis, we conclude that the ivy
      nanoparticles are proteinaceous. 

PMID- 23883949
TI  - Analysing photonic structures in plants.
AB  - The outer layers of a range of plant tissues, including flower petals, leaves and
      fruits, exhibit an intriguing variation of microscopic structures. Some of these
      structures include ordered periodic multilayers and diffraction gratings that
      give rise to interesting optical appearances. The colour arising from such
      structures is generally brighter than pigment-based colour. Here, we describe the
      main types of photonic structures found in plants and discuss the experimental
      approaches that can be used to analyse them. These experimental approaches allow
      identification of the physical mechanisms producing structural colours with a
      high degree of confidence. 

PMID- 23883951
TI  - Interpretation of body-mounted accelerometry in flying animals and estimation of
      biomechanical power.
AB  - An idealized energy fluctuation model of a bird's body undergoing horizontal
      flapping flight is developed, focusing on the biomechanical power discernible to
      a body-mounted accelerometer. Expressions for flight body power constructed from
      root mean square dynamic body accelerations and wingstroke frequency are derived
      from first principles and presented in dimensionally appropriate units. As
      wingstroke frequency increases, the model generally predicts a gradual transition
      in power from a linear to an asymptotically cubic relationship. However, the
      onset of this transition and the degree to which this occurs depends upon whether
      and how forward vibrations are exploited for temporary energy storage and
      retrieval. While this may vary considerably between species and individual birds,
      it is found that a quadrature phase arrangement is generally advantageous during
      level flight. Gravity-aligned vertical acceleration always enters into the
      calculation of body power, but, whenever forward acceleration becomes relevant,
      its contribution is subtractive. Several novel kinematic measures descriptive of
      flapping flight are postulated, offering fresh insights into the processes
      involved in airborne locomotion. The limitations of the model are briefly
      discussed, and departures from its predictions during ascending and descending
      flight evaluated. These findings highlight how body-mounted accelerometers can
      offer a valuable, insightful and non-invasive technique for investigating the
      flight of free-ranging birds and bats. 

PMID- 23883950
TI  - Bioavailability of silver nanoparticles and ions: from a chemical and biochemical
      perspective.
AB  - Owing to their antimicrobial properties, silver nanoparticles (NPs) are the most
      commonly used engineered nanomaterial for use in a wide array of consumer and
      medical applications. Many discussions are currently ongoing as to whether or not
      exposure of silver NPs to the ecosystem (i.e. plants and animals) may be
      conceived as harmful or not. Metallic silver, if released into the environment,
      can undergo chemical and biochemical conversion which strongly influence its
      availability towards any biological system. During this process, in the presence
      of moisture, silver can be oxidized resulting in the release of silver ions. To
      date, it is still debatable as to whether any biological impact of nanosized
      silver is relative to either its size, or to its ionic constitution. The aim of
      this review therefore is to provide a comprehensive, interdisciplinary overview-
      for biologists, chemists, toxicologists as well as physicists--regarding the
      production of silver NPs, its (as well as in their ionic form) chemical and
      biochemical behaviours towards/within a multitude of relative and realistic
      biological environments and also how such interactions may be correlated across a
      plethora of different biological organisms.

PMID- 23883952
TI  - A hybrid approach to simulation of electron transfer in complex molecular
      systems.
AB  - Electron transfer (ET) reactions in biomolecular systems represent an important
      class of processes at the interface of physics, chemistry and biology. The
      theoretical description of these reactions constitutes a huge challenge because
      extensive systems require a quantum-mechanical treatment and a broad range of
      time scales are involved. Thus, only small model systems may be investigated with
      the modern density functional theory techniques combined with non-adiabatic
      dynamics algorithms. On the other hand, model calculations based on Marcus's
      seminal theory describe the ET involving several assumptions that may not always
      be met. We review a multi-scale method that combines a non-adiabatic propagation
      scheme and a linear scaling quantum-chemical method with a molecular mechanics
      force field in such a way that an unbiased description of the dynamics of excess
      electron is achieved and the number of degrees of freedom is reduced effectively
      at the same time. ET reactions taking nanoseconds in systems with hundreds of
      quantum atoms can be simulated, bridging the gap between non-adiabatic ab initio
      simulations and model approaches such as the Marcus theory. A major recent
      application is hole transfer in DNA, which represents an archetypal ET reaction
      in a polarizable medium. Ongoing work focuses on hole transfer in proteins,
      peptides and organic semi-conductors. 

PMID- 23883953
TI  - In vivo optic nerve head biomechanics: performance testing of a three-dimensional
      tracking algorithm.
AB  - Measurement of optic nerve head (ONH) deformations could be useful in the
      clinical management of glaucoma. Here, we propose a novel three-dimensional
      tissue-tracking algorithm designed to be used in vivo. We carry out preliminary
      verification of the algorithm by testing its accuracy and its robustness. An
      algorithm based on digital volume correlation was developed to extract ONH tissue
      displacements from two optical coherence tomography (OCT) volumes of the ONH
      (undeformed and deformed). The algorithm was tested by applying artificial
      deformations to a baseline OCT scan while manipulating speckle noise,
      illumination and contrast enhancement. Tissue deformations determined by our
      algorithm were compared with the known (imposed) values. Errors in displacement
      magnitude, orientation and strain decreased with signal averaging and were 0.15
      um, 0.15 degrees  and 0.0019, respectively (for optimized algorithm parameters).
      Previous computational work suggests that these errors are acceptable to provide
      in vivo characterization of ONH biomechanics. Our algorithm is robust to OCT
      speckle noise as well as to changes in illumination conditions, and increasing
      signal averaging can produce better results. This algorithm has potential be used
      to quantify ONH three-dimensional strains in vivo, of benefit in the diagnosis
      and identification of risk factors in glaucoma. 

PMID- 23883954
TI  - Simplifying biochemical models with intermediate species.
AB  - Mathematical models are increasingly being used to understand complex biochemical
      systems, to analyse experimental data and make predictions about unobserved
      quantities. However, we rarely know how robust our conclusions are with respect
      to the choice and uncertainties of the model. Using algebraic techniques, we
      study systematically the effects of intermediate, or transient, species in
      biochemical systems and provide a simple, yet rigorous mathematical
      classification of all models obtained from a core model by including
      intermediates. Main examples include enzymatic and post-translational
      modification systems, where intermediates often are considered insignificant and
      neglected in a model, or they are not included because we are unaware of their
      existence. All possible models obtained from the core model are classified into a
      finite number of classes. Each class is defined by a mathematically simple
      canonical model that characterizes crucial dynamical properties, such as mono-
      and multistationarity and stability of steady states, of all models in the class.
      We show that if the core model does not have conservation laws, then the
      introduction of intermediates does not change the steady-state concentrations of
      the species in the core model, after suitable matching of parameters.
      Importantly, our results provide guidelines to the modeller in choosing between
      models and in distinguishing their properties. Further, our work provides a
      formal way of comparing models that share a common skeleton. 

PMID- 23883955
TI  - The cost of sensitive response and accurate adaptation in networks with an
      incoherent type-1 feed-forward loop.
AB  - The incoherent type-1 feed-forward loop (I1-FFL) is ubiquitous in biological
      regulatory circuits. Although much is known about the functions of the I1-FFL
      motif, the energy cost incurred in the network and how it affects the performance
      of the network have not been investigated. Here, we study a generic I1-FFL
      enzymatic reaction network modelled after the GEF-GAP-Ras pathway responsible for
      chemosensory adaptation in eukaryotic cells. Our analysis shows that the I1-FFL
      network always operates out of equilibrium. Continuous energy dissipation is
      necessary to drive an internal phosphorylation-dephosphorylation cycle that is
      crucial in achieving strong short-time response and accurate long-time
      adaptation. In particular, we show quantitatively that the energy dissipated in
      the I1-FFL network is used (i) to increase the system's initial response to the
      input signals; (ii) to enhance the adaptation accuracy at steady state; and (iii)
      to expand the range of such accurate adaptation. Moreover, we find that the
      energy dissipation rate, the catalytic speed and the maximum adaptation accuracy
      in the I1-FFL network satisfy the same energy-speed-accuracy relationship as in
      the negative-feedback-loop (NFL) networks. Because the I1-FFL and NFL are the
      only two basic network motifs that enable accurate adaptation, our results
      suggest that a universal cost-performance trade-off principle may underlie all
      cellular adaptation processes independent of the detailed biochemical circuit
      architecture. 

PMID- 23883956
TI  - Enhanced signal-to-noise ratios in frog hearing can be achieved through amplitude
      death.
AB  - In the ear, hair cells transform mechanical stimuli into neuronal signals with
      great sensitivity, relying on certain active processes. Individual hair cell
      bundles of non-mammals such as frogs and turtles are known to show spontaneous
      oscillation. However, hair bundles in vivo must be quiet in the absence of
      stimuli, otherwise the signal is drowned in intrinsic noise. Thus, a certain
      mechanism is required in order to suppress intrinsic noise. Here, through a model
      study of elastically coupled hair bundles of bullfrog sacculi, we show that a low
      stimulus threshold and a high signal-to-noise ratio (SNR) can be achieved through
      the amplitude death phenomenon (the cessation of spontaneous oscillations by
      coupling). This phenomenon occurs only when the coupled hair bundles have
      inhomogeneous distribution, which is likely to be the case in biological systems.
      We show that the SNR has non-monotonic dependence on the mass of the overlying
      membrane, and find out that the SNR has maximum value in the region of amplitude
      death. The low threshold of stimulus through amplitude death may account for the
      experimentally observed high sensitivity of frog sacculi in detecting vibration.
      The hair bundles' amplitude death mechanism provides a smart engineering design
      for low-noise amplification. 

PMID- 23883957
TI  - Emergence of polar order and cooperativity in hydrodynamically coupled model
      cilia.
AB  - As a model of ciliary beat, we use two-state oscillators that have a defined
      direction of oscillation and have strong synchronization properties. By allowing
      the direction of oscillation to vary according to the interaction with the fluid,
      with a timescale longer than the timescale of synchronization, we show in
      simulations that several oscillators can align in a direction set by the
      geometrical configuration of the system. In this system, the alignment depends on
      the state of synchronization of the system, and is therefore linked to the beat
      pattern of the model cilia. By testing various configurations from two to 64
      oscillators, we deduce empirically that, when the synchronization state of
      neighbouring oscillators is in phase, the angles of the oscillators align in a
      configuration of high hydrodynamic coupling. In arrays of oscillators that break
      the planar symmetry, a global direction of alignment emerges reflecting this
      polarity. In symmetric configurations, where several directions are geometrically
      equivalent, the array still displays strong internal cooperative behaviour. It
      also appears that the shape of the array is more important than the lattice type
      and orientation in determining the preferred direction. 

PMID- 23883959
TI  - Consecutive fecal calprotectin measurements to predict relapse in patients with
      ulcerative colitis receiving infliximab maintenance therapy.
AB  - BACKGROUND: This study examined whether fecal calprotectin can be used in daily
      practice as a marker to monitor patients with ulcerative colitis (UC) receiving
      infliximab maintenance therapy. METHODS: This prospective multicenter study
      enrolled adult patients with UC in clinical remission under infliximab
      maintenance therapy. Fecal calprotectin levels were measured every 4 weeks.
      Sigmoidoscopies were performed at inclusion and at study end. Relapse was defined
      as a clinical need for change in treatment or an endoscopic Mayo subscore of >=2
      at week 52. Sustained deep remission was defined as a partial Mayo score <3 at
      all points and an endoscopic Mayo score 0 at week 52. RESULTS: Full analysis was
      possible for 87 of 113 included patients with UC (77%). Of these patients, 30
      (34.4%) were considered to be in sustained deep remission and 13 (14.9%) to have
      relapsed. Calprotectin levels in patients with sustained deep remission remained
      very low (median < 40 mg/kg at all time points). Patients who flared had
      significantly higher calprotectin levels (median > 300 mg/kg) already 3 months
      before the flare. Further receiver operator curve analysis suggested that a
      calprotectin level >300 mg/kg had a reasonable sensitivity (58.3%) and
      specificity (93.3%) to model flare. Two consecutive calprotectin measurements of
      >300 mg/kg with 1-month interval were identified as the best predictor of flare
      (61.5% sensitivity and 100% specificity). CONCLUSIONS: Fecal calprotectin can be
      used in daily practice to monitor patients with UC receiving infliximab
      maintenance therapy. Two consecutive measurements >300 mg/kg is more specific
      than a single measurement for predicting relapse.

PMID- 23883960
TI  - Feasibility of venous thromboembolism prophylaxis during inflammatory bowel
      disease flares in the outpatient setting: a decision analysis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of
      venous thromboembolism (VTE), which is most pronounced during a disease flare. We
      explored the cost-effectiveness of pharmacological VTE prophylaxis in an
      outpatient setting. METHODS: Markov decision analysis was conducted from a
      societal perspective to compare the relative costs and effectiveness of
      pharmacological VTE prophylaxis versus no anticoagulation during ambulatory IBD
      flares among a hypothetical cohort of 10,000 IBD patients. The time horizon was
      from time of IBD diagnosis until death. Univariate and probabilistic sensitivity
      analyses were performed. RESULTS: In base case analysis, VTE prophylaxis was,
      compared with no anticoagulation, associated with higher average costs (U.S.
      $141,036 versus $90,338) and quality-adjusted life-years (QALYs) (22.29 versus
      22.25), yielding an incremental cost-effectiveness ratio of $1,267,450/QALY.
      Venous thromboembolism prophylaxis resulted in higher unadjusted life-years
      (47.76 life-years versus 46.67 life-years) and lower lifetime risk of VTE (6.2%
      versus 9.3%). The number needed to treat to prevent one VTE event over a lifetime
      was 32.3. Univariate sensitivity analysis showed that the incremental cost
      effectiveness ratio was most sensitive to variations in the efficacy of VTE
      prophylaxis. In probabilistic sensitivity analysis, only 20% of 1000 simulated
      trials showed that VTE prophylaxis increased QALYs. In the remaining 80%, it was
      associated with both higher costs and fewer QALYs. CONCLUSIONS: Although the
      administration of pharmacological VTE prophylaxis during IBD flares in the
      outpatient setting was associated with increased life-years and reduced VTE
      events, it was not cost effective. Moreover, the benefits of VTE prophylaxis were
      not robust to probabilistic sensitivity analysis.

PMID- 23883961
TI  - Improved axonal regeneration of transected spinal cord mediated by multichannel
      collagen conduits functionalized with neurotrophin-3 gene.
AB  - Functionalized biomaterial scaffolds targeted at improving axonal regeneration by
      enhancing guided axonal growth provide a promising approach for the repair of
      spinal cord injury. Collagen neural conduits provide structural guidance for
      neural tissue regeneration, and in this study it is shown that these conduits can
      also act as a reservoir for sustained gene delivery. Either a G-luciferase marker
      gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized,
      PEGylated transfection vector, was loaded within a multichannel collagen conduit.
      The complexed genes were then released in a controlled fashion using a dual
      release system both in vitro and in vivo. For evaluation of their biological
      performance, the loaded conduits were implanted into the completely transected
      rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels
      of conduits was observed one month post-surgery. The conduits delivering
      neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3
      levels in the surrounding tissue and a statistically higher number of regenerated
      axons versus the control conduits (P<0.05). This study suggests that collagen
      neural conduits delivering a highly effective non-viral therapeutic gene may hold
      promise for repair of the injured spinal cord. 

PMID- 23883962
TI  - PEGylated helper-dependent adenoviral vector expressing human Apo A-I for gene
      therapy in LDLR-deficient mice.
AB  - Helper-dependent adenoviral (HD-Ad) vectors have great potential for gene therapy
      applications; however, their administration induces acute toxicity that impairs
      safe clinical applications. We previously observed that PEGylation of HD-Ad
      vectors strongly reduces the acute response in murine and primate models. To
      evaluate whether PEGylated HD-Ad vectors combine reduced toxicity with the
      correction of pathological phenotypes, we administered an HD-Ad vector expressing
      the human apolipoprotein A-I (hApoA-I) to low-density lipoprotein (LDL)-receptor
      deficient mice (a model for familial hypercholesterolemia) fed a high-cholesterol
      diet. Mice were treated with high doses of HD-Ad-expressing apo A-I or its
      PEGylated version. Twelve weeks later, LDL levels were lower and high-density
      lipoprotein (HDL) levels higher in mice treated with either of the vectors than
      in untreated mice. After terminal killing, the areas of atherosclerotic plaques
      were much smaller in the vector-treated mice than in the control animals.
      Moreover, the increase in pro-inflammatory cytokines was lower and consequently
      the toxicity profile better in mice treated with PEGylated vector than in mice
      treated with the unmodified vector. This finding indicates that the reduction in
      toxicity resulting from PEGylation of HD-Ad vectors does not impair the
      correction of pathological phenotypes. It also supports the clinical potential of
      these vectors for the correction of genetic diseases. 

PMID- 23883963
TI  - Immunogenetics: serving up variation to fight adversity.

PMID- 23883970
TI  - Long-term functions of encapsulated islets grafted in nonhuman primates without
      immunosuppression.
AB  - BACKGROUND: Long-term survival and functions of encapsulated islet grafts need to
      be evaluated in the absence of immunosuppression. The present study aimed to
      assess the viability and functions of macroencapsulated islets grafted in
      nonhuman primates without immunosuppression for 1 year. METHODS: Islet
      transplantations were performed in partially pancreatectomized rhesus monkeys
      (two autologous and four allogenic) without immunosuppression using
      immunoisolatory devices. Macroencapsulated islets were implanted subcutaneously
      (5000-8000 IEQ/device) at two sites (left thigh and interscapular region) and
      were explanted at 2, 6, and 12 months after implantation. Staining for viability
      and apoptosis, in vivo and in vitro glucose-stimulated insulin release,
      expression of insulin and glucagon genes, and histopathologic examination of the
      device were used to assess engraftment potential, viability, and functions of
      islets. Animals were regularly monitored for dietary intake, body weight, and
      fasting blood glucose levels after islet transplantation. RESULTS: Devices
      explanted showed vascularization at the end of 2, 6, and 12 months with
      occasional lymphocytes and minimal fibrosis outside the device. Flow cytometric
      analysis revealed 97.9%+/-1.5% and 94.3%+/-5.71% viable beta cells in
      interscapular site and thigh in autologous recipients and 85.6%+/-4.01%
      (interscapular site) and 74.1%+/-12.05% (thigh) viable beta cells in allogenic
      islet recipients. In vivo glucose challenge test revealed significantly increased
      glucose-stimulated insulin release (P=0.028) in the left thigh with implant
      (17.58+/-3.13 mU/L) compared with the thigh without implant (9.86+/-1.063 mU/L).
      Insulin and glucagon gene expression was evident in islets recovered from
      explanted device. CONCLUSIONS: These results indicate that subcutaneous
      implantation of macroencapsulated islets is minimally invasive and has potential
      for transplantation without immunosuppression.

PMID- 23883968
TI  - New insights into pre-BCR and BCR signalling with relevance to B cell
      malignancies.
AB  - The B cell receptor (BCR) and its precursor (pre-BCR) control B cell homeostasis,
      differentiation and function. Moreover, aberrant pre-BCR and BCR signalling have
      a central role in B cell neoplasia; for example, enhanced positive signalling or
      disrupted negative signalling downstream of the pre-BCR promotes B cell acute
      lymphocytic leukaemia. The emerging distinctions between tonic and chronic active
      BCR signalling have contributed to the identification of oncogenic targets
      downstream of BCR signalling in mature B cell neoplasms. Indeed, the encouraging
      results of several ongoing clinical trials that target the activity of
      phosphoinositide 3-kinase delta-isoform (PI3Kdelta), Bruton tyrosine kinase (BTK)
      or spleen tyrosine kinase (SYK) downstream of the BCR highlight the therapeutic
      potential of inhibiting BCR signalling. 

PMID- 23883969
TI  - Applications of nanotechnology for immunology.
AB  - Nanotechnology uses the unique properties of objects that function as a unit
      within the overall size range of 1-1,000 nanometres. The engineering of
      nanostructure materials, including nanoparticles, nanoemulsions or nanotubules,
      holds great promise for the development of new immunomodulatory agents, as such
      nanostructures can be used to more effectively manipulate or deliver
      immunologically active components to target sites. Successful applications of
      nanotechnology in the field of immunology will enable new generations of
      vaccines, adjuvants and immunomodulatory drugs that aim to improve clinical
      outcomes in response to a range of infectious and non-infectious diseases. 

PMID- 23883971
TI  - Inhibitory effects of belatacept on allospecific regulatory T-cell generation in
      humans.
AB  - BACKGROUND: It is unclear if new costimulatory blockade agents, such as the
      cytotoxic T lymphocyte-associated antigen 4-Ig molecule belatacept (BEL), promote
      or inhibit the potential for immunologic tolerance in transplantation. We
      therefore tested the in vitro effects of BEL on human regulatory T cells (Tregs)
      in mixed lymphocyte reactions (MLR) alone and in combination with maintenance
      agents used in transplant recipients. METHODS: BEL, mycophenolic acid (MPA), and
      sirolimus, either alone or in combination, were added to healthy volunteer Treg
      MLR, testing (a) H-TdR incorporation for inhibition of lymphoproliferation and
      (b) flow cytometry to analyze for newly generated CD4+ CD25(high) FOXP3+ Tregs in
      carboxyfluorescein succinimidyl ester-labeled MLR responders. In addition, the
      modulatory effects of putative Tregs generated in the presence of these drugs
      were also tested using the lymphoproliferation and flow cytometric assays.
      RESULTS: In comparison with medium controls, BEL dose-dependently inhibited both
      lymphoproliferation and Treg generation in human leukocyte antigen DR matched and
      mismatched MLRs either alone or in combination with MPA or sirolimus. However,
      MPA alone inhibited lymphoproliferation but significantly enhanced Treg
      generation at subtherapeutic concentrations (P<0.01). In addition, purified CD4+
      CD127- cells generated in MLR in the presence of MPA and added as third component
      modulators in fresh MLRs significantly enhanced newly developed Tregs in the
      proliferating responder cells compared with those generated with BEL or medium
      controls. CONCLUSIONS: BEL alone and in combination with agents used in
      transplant recipients inhibits the in vitro generation of human Tregs. BEL might
      therefore be a less optimal agent for tolerance induction in human organ
      transplantation.

PMID- 23883972
TI  - Assessing the effect of immunosuppression on engraftment of pancreatic islets.
AB  - BACKGROUND: In addition to ischemia and immunologic factors, immunosuppressive
      drugs have been suggested as a possible contributing factor to the loss of
      functional islets after allogeneic islet cell transplantation. Using our
      previously described islet-kidney (IK) transplantation model in miniature swine,
      we studied whether an islet-toxic triple-drug immunosuppressive regimen
      (cyclosporine+azathioprine+prednisone) affects the islet engraftment process and
      thus long-term islet function. METHODS: Donor animals underwent partial
      pancreatectomy, autologous islet preparation, and injection of these islets under
      the autologous kidney capsule to prepare an IK. Experimental animals received
      daily triple-drug immunosuppression during the islet engraftment period. Control
      animals did not receive any immunosuppression during this period. Four to 8 weeks
      later, these engrafted IK were transplanted across a minor histocompatibility
      mismatched barrier into pancreatectomized, nephrectomized recipient animals at an
      islet dose of approximately 4500 islet equivalents/kg recipient weight.
      Cyclosporine was administered for 12 days to the recipients to induce tolerance
      of the IK grafts and the animals were followed long-term. RESULTS: Diabetes was
      corrected by IK transplantation in all pancreatectomized recipients on both the
      control arm (n=3) and the experimental arm (n=4) of the study and all animals
      showed normal glucose regulation over the follow-up period. Intravenous glucose
      tolerance tests performed at 1, 2, and 3 or more months after IK transplantation
      showed essentially equivalent glycemic control in both control and experimental
      animals. CONCLUSION: In this preclinical in vivo large animal model of islet
      transplantation, the effect of triple-drug immunosuppression on islet function
      does not negatively affect islet engraftment as assessed by the long-term
      function of engrafted islets.

PMID- 23883974
TI  - Elevated expression of notch1 is associated with metastasis of human
      malignancies.
AB  - The expression level of Notch1 has been studied in many primary tumor types, but
      has not been widely investigated in metastatic lesions from human malignancies.
      Using immunohistochemistry (IHC), the expression level of Notch1 was evaluated
      and compared between primary and metastatic tumors in 12 different cancers. The
      mean IHC score of Notch1 was significantly increased in metastatic hepatocellular
      carcinoma (HCC; 5.4 +/- 0.7) and in metastatic renal cell carcinoma (RCC; 5.0 +/-
      2.3) compared with primary HCC (3.1 +/- 0.7, P = .035) and RCC (1.3 +/- 0.6, P =
      .049), respectively. Similarly, the expression level of Notch1 showed an
      increasing trend in the metastatic malignancies in the larynx, prostate, and
      stomach compared with corresponding primary malignancies (P values are .055,
      .072, and .074, respectively). The results demonstrate elevated expression of
      Notch1 in some metastatic tumors, suggesting that Notch1 may play an important
      role in the development or maintenance of metastatic lesions, and targeting of
      Notch1 might be a therapeutic approach against tumor metastasis. 

PMID- 23883973
TI  - Risk factors and outcomes of bacteremia caused by drug-resistant ESKAPE pathogens
      in solid-organ transplant recipients.
AB  - BACKGROUND: Although infections due to the six ESKAPE pathogens have recently
      been identified as a serious emerging problem, information regarding bacteremia
      caused by these organisms in solid-organ transplant (SOT) recipients is lacking.
      We sought to determine the frequency, risk factors, and outcomes of bacteremia
      due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart
      adult transplant recipients. METHODS: All episodes of bacteremia prospectively
      documented in hospitalized SOT recipients from 2007 to 2012 were analyzed.
      RESULTS: Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains
      (vancomycin-resistant Enterococcus faecium [0], methicillin-resistant
      Staphylococcus aureus [5], extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae [10], carbapenem-resistant Acinetobacter baumannii [8], carbapenem-
      and quinolone-resistant Pseudomonas aeruginosa [26], and derepressed chromosomal
      beta-lactam and extended-spectrum beta-lactamase-producing Enterobacter species
      [5]). Factors independently associated with rESKAPE bacteremia were prior
      transplantation, septic shock, and prior antibiotic therapy. Patients with
      rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy
      than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was
      higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001).
      CONCLUSIONS: Bacteremia due to rESKAPE pathogens is frequent in SOT recipients
      and causes significant morbidity and mortality. rESKAPE organisms should be
      considered when selecting empirical antibiotic therapy for hospitalized SOT
      recipients presenting with septic shock, particularly those with prior
      transplantation and antibiotic use.

PMID- 23883975
TI  - Role of p16, CK17, p63, and human papillomavirus in diagnosis of cervical
      intraepithelial neoplasia and distinction from its mimics.
AB  - BACKGROUND: Diagnosis of cervical intraepithelial neoplasia (CIN), the precursor
      forms of cervical cancer, can be tricky and it has led to discrepancy between
      pathologists in distinguishing them from its mimics such as atypical immature
      metaplasia (AIM), immature squamous metaplasia (ISM), reactive atypia (RA),
      atrophy, and basal cell hyperplasia (BCH). To overcome this problem this study
      aims at using immunohistochemical (IHC) markers p16, p63, CK17, and human
      papillomavirus (HPV) to differentiate CIN from its mimics. MATERIALS AND METHODS:
      This study analyzed 350 cervical samples with histomorphological diagnosis of CIN
      and its mimics and the utility of IHC markers p16, p63, CK17, and HPV in
      distinction was analyzed. RESULTS: p16 showed 67.76% sensitivity and 99.4%
      specificity whereas HPV showed 57.9% sensitivity and 91.6% specificity in
      detecting CIN. CK17 and p63 did not show any significance in distinguishing CIN
      from its mimics. After IHC of AIM cases, 66.7% were reclassified as CIN III,
      27.8% as ISM with reactive atypia (ISMRA), and 5.5% case as immature condyloma.
      In total, 3.7% of diagnosis was upgraded to CIN and 0.6% of pre-IHC diagnosis was
      downgraded from CIN to reactive lesions. CONCLUSION: IHC panel comprising p16,
      p63, CK17, and HPV are useful adjuncts in distinguishing CIN from its mimics
      particularly when histomorphology has overlapping morphological features.

PMID- 23883977
TI  - Nurses: patient advocates, positive deviants?

PMID- 23883976
TI  - The role of 1-deoxy-d-xylulose-5-phosphate synthase and phytoene synthase gene
      family in citrus carotenoid accumulation.
AB  - Three 1-deoxy-D-xylulose-5-phosphate synthases (DXS) and three phytoene synthases
      (PSY) were identified in citrus, from Affymetrix GeneChip Citrus Genome Array,
      GenBank and public orange genome databases. Tissue-specific expression analysis
      of these genes was carried out on fruit peel and flesh, flower and leaf of
      Satsuma mandarin (Citrus unshiu Marc.) in order to determine their roles in
      carotenoid accumulation in different tissues. Expression of CitDXS1 and CitPSY1
      was highest in all test tissues, while that of CitDXS2 and CitPSY2 was lower, and
      that of CitDXS3 and CitPSY3 undetectable. The transcript profiles of CitDXS1 and
      CitPSY1 paralleled carotenoid accumulation in flesh of Satsuma mandarin and
      orange (Citrus sinensis Osbeck) during fruit development, and CitPSY1 expression
      was also associated with carotenoid accumulation in peel, while the CitDXS1
      transcript level was only weakly correlated with carotenoid accumulation in peel.
      Similar results were obtained following correlation analysis between expression
      of CitDXS1 and CitPSY1 and carotenoid accumulation in peel and flesh of 16 citrus
      cultivars. These findings identify CitPSY1 and CitDXS1 as the main gene members
      controlling carotenoid biosynthesis in citrus fruit. Furthermore, chromoplasts
      were extracted from flesh tissue of these citrus, and chromoplasts of different
      shape (spindle or globular), different size, and color depth were observed in
      different cultivars, indicating chromoplast abundance, number per gram tissue,
      size and color depth were closely correlated with carotenoid content in most
      cultivars. The relationship between carotenoid biosynthesis and chromoplast
      development was discussed.

PMID- 23883978
TI  - Physician orders.

PMID- 23883979
TI  - Report on abortion.

PMID- 23883980
TI  - PSA screening.

PMID- 23883981
TI  - Variations in hospital charges for inpatient procedures.

PMID- 23883982
TI  - Taking health to the streets.

PMID- 23883984
TI  - RN staffing improves rural heart failure care.

PMID- 23883985
TI  - A freestanding birthing center trumps hospitals.

PMID- 23883986
TI  - Can sodium intake recommendations be too low?

PMID- 23883989
TI  - Better nurse staffing improves outcomes in children, too.

PMID- 23883993
TI  - Nurse-patient staffing ratios.

PMID- 23883999
TI  - Using focus groups to inform innovative approaches to care.

PMID- 23884000
TI  - Autologous platelet-rich plasma for treating chronic wounds.

PMID- 23884001
TI  - Buurtzorg Nederland.

PMID- 23884002
TI  - Measuring wounds to improve outcomes.

PMID- 23884007
TI  - Teaching nurses in Bangladesh.

PMID- 23884008
TI  - House of death, house of life.

PMID- 23884009
TI  - Uniaxial alignment of triisopropylsilylethynyl pentacene via zone-casting
      technique.
AB  - Uniaxially aligned triisopropylsilylethynyl pentacene (TIPS-pentacene) crystals
      over a large area were fabricated using zone-casting technique. The array of TIPS
      pentacene displayed a high orientation degree with a dichroic ratio (DR) of 0.80.
      The crystals were arranged with c axis perpendicular to the substrate and the
      long axis of the ribbon corresponded to the a axis of TIPS-pentacene. The
      properties of the solutions and the processing parameters were shown to influence
      the formation of the oriented TIPS-pentacene crystalline array. Solvent with a
      low boiling point (such as chloroform) favoured the orientation of the ribbon
      like crystals. The concentration of the solution should be appropriate, ensuring
      the crystallization velocity of TIPS-pentacene matching with the receding of the
      meniscus. Besides, we proved that the casting speed should be large enough to
      induce a sufficient concentration gradient. The orientation mechanism of TIPS
      pentacene was attributed to a synergy of the ordered nuclei and a match between
      the crystallization velocity and the casting speed. Field effect transistors
      (FETs) based on the oriented TIPS-pentacene crystalline array showed a mobility
      of 0.67 cm(2) V(-1) s(-1). 

PMID- 23884010
TI  - Strength and Debye temperature measurements of cerium across the gamma -> alpha
      volume collapse: the lattice contribution.
AB  - The longitudinal and transverse sound speeds, cL and cT, of polycrystalline
      cerium were measured under pressure across the iso-structural gamma-alpha phase
      transition at 0.75 GPa to beyond 3 GPa. In contrast to previous methods all
      quantities were directly obtained and no assumptions were made about the size of
      the volume collapse. Up to the transition our values for cL are in excellent
      agreement with previous ones, while our values for cT are significantly lower. We
      deduce values for the adiabatic bulk modulus BS, the shear modulus [Formula: see
      text], and the pressure dependent Debye temperature, ThetaD(p). ThetaD(p) is in
      good agreement with recent results derived from phonon dispersion measurements on
      single crystals. The ratio of the Debye temperature values bracketing the
      transition indicates a lattice contribution to the entropy change across the
      volume collapse, DeltaSvib(gamma -> alpha) ~ (0.68 +/- 0.06)kB, consistent with
      previous results obtained by neutron scattering, but significantly larger than
      other previously determined values. 

PMID- 23884011
TI  - News media representations of electronic cigarettes: an analysis of newspaper
      coverage in the UK and Scotland.
AB  - OBJECTIVE: Electronic Nicotine Delivery Systems (ENDS) have recently been
      attracting interest for their potential as a less harmful alternative to smoking,
      their rising popularity and the regulatory issues they raise. The news media can
      play an important role in shaping public perceptions of new technologies. It is,
      therefore, important to understand the ways the news media present ENDS. This
      paper examines how ENDS are represented in the UK and in the Scottish press.
      METHODS: Twelve national UK and Scottish newspapers and the three most popular
      online news sources were searched between 2007 and 2012. A thematic analysis was
      conducted to explore how the meanings, uses and users of ENDS are presented, and
      whether and how this has changed. RESULTS: Newspaper coverage of ENDS increased
      substantially over this period. Five key themes emerged from the analysis:
      getting around smokefree legislation; risk and uncertainty; healthier choice;
      celebrity use; price. CONCLUSIONS: Drawing on the diffusion of innovations
      theory, we suggest that newspaper constructions of ENDS provide readers with
      important information about what ENDS are for, how they work, and their relative
      advantages. These themes, and dominance of more positive meanings, raise a number
      of issues for tobacco control, including concerns around celebrity use and
      promotion; the impact of increasing ENDS use on social norms around smoking;
      their potential to undermine smokefree legislation; and their promotion as
      effective cessation aids.

PMID- 23884013
TI  - Assisted bicycle training delays functional deterioration in boys with Duchenne
      muscular dystrophy: the randomized controlled trial "no use is disuse".
AB  - BACKGROUND: Physical training might delay the functional deterioration caused by
      disuse in boys with Duchenne muscular dystrophy (DMD). The "No Use Is Disuse"
      study is the first explorative, randomized controlled trial in boys with DMD to
      examine whether assisted bicycle training is feasible, safe, and beneficial.
      METHODS: Ambulatory and recently wheelchair-dependent boys with DMD were
      allocated to the intervention or control group. The intervention group received
      assisted bicycle training of the legs and arms during 24 weeks. The control group
      received the same training after a waiting period of 24 weeks. The primary study
      outcomes were the Motor Function Measure (MFM) and the Assisted 6-Minute Cycling
      Test (A6MCT). Group differences were examined by an analysis of covariance.
      RESULTS: Thirty boys (mean age 10.5 +/- 2.6 years, 18 ambulant and 12 wheelchair
      dependent) were allocated to the intervention (n = 17) or the control (n = 13)
      group. All boys in the intervention group (except one) completed the training.
      After 24 weeks, the total MFM score remained stable in the intervention group,
      whereas it had significantly decreased in the control group (Delta = 4.9, 95%
      confidence interval = 2.2-7.6). No significant group differences were found for
      the A6MCT. No serious adverse events were observed. CONCLUSIONS: Our results
      suggest that assisted bicycle training of the legs and arms is feasible and safe
      for both ambulant and wheelchair-dependent children and may decline the
      deterioration due to disuse. Progressive deterioration, however, may compromise
      the design of trials for DMD.

PMID- 23884014
TI  - Characteristics of exercise training interventions to improve cardiorespiratory
      fitness after stroke: a systematic review with meta-analysis.
AB  - BACKGROUND: Cardiorespiratory fitness is low after stroke. Improving fitness has
      the potential to improve function and reduce secondary cardiovascular events.
      OBJECTIVE: . This review with meta-analysis aims to identify characteristics and
      determine the effectiveness of interventions to improve cardiorespiratory fitness
      after stroke. METHODS: A systematic search and review with meta-analysis was
      undertaken. Key inclusion criteria were the following: peer-reviewed articles
      published in English, adult stroke survivors, an intervention with the potential
      to improve cardiorespiratory fitness, and peak oxygen consumption (VO2peak)
      assessed preintervention and postintervention via a progressive aerobic exercise
      test. RESULTS: From 3209 citations identified, 28 studies were included,
      reporting results for 920 participants. Studies typically included chronic,
      ambulant participants with mild to moderate deficits; used an aerobic or mixed
      (with an aerobic component) intervention; and prescribed 3 sessions per week for
      30 to 60 minutes per session at a given intensity. Baseline VO2peak values were
      low (8-23 mL/kg/min). Meta-analysis of the 12 randomized controlled trials
      demonstrated overall improvements in VO2peak of 2.27 (95% confidence interval =
      1.58, 2.95) mL/kg/min postintervention. A similar 10% to 15% improvement occurred
      with both aerobic and mixed interventions and in shorter (<= 3 months) and longer
      (>3 months) length programs. Only 1 study calculated total dose received and only
      1 included long-term follow-up. CONCLUSIONS: The results demonstrate that
      interventions with an aerobic component can improve cardiorespiratory fitness
      poststroke. Further investigation is required to determine effectiveness in those
      with greater impairment and comorbidities, optimal timing and dose of
      intervention, whether improvements can be maintained in the longer term, and
      whether improved fitness results in better function and reduced risk of
      subsequent cardiovascular events.

PMID- 23884015
TI  - Understanding adaptive motor control of the paretic upper limb early poststroke:
      the EXPLICIT-stroke program.
AB  - BACKGROUND: During upper limb motor recovery after stroke, the greatest
      improvements occur typically in the first 5 weeks poststroke. It is unclear what
      patients learn during this early phase of recovery. OBJECTIVE: To investigate the
      hypothesis that, early poststroke, patients learn to master the degrees of
      freedom in the paretic upper limb as reflected by dissociated shoulder and elbow
      movements during reach-to-grasp. METHODS: Thirty-one patients with a first-ever
      ischemic stroke were included. Repeated 3-dimensional kinematic measurements were
      conducted at 14, 25, 38, 57, 92, and 189 days poststroke. Trunk, shoulder, elbow,
      and wrist rotations were measured during a reach-to-grasp task. Using principal
      component analysis the longitudinal changes in dissociated upper limb movements
      during reach-to-grasp were investigated. Twelve healthy subjects were included
      for comparison. RESULTS: The main coordination pattern during reach-to-grasp in
      patients with stroke and healthy subjects consisted mostly of horizontal shoulder
      adduction and elbow extension. The standard deviation of this main pattern
      increased over time, with the largest increase in the first 5 weeks poststroke (F
      = 5.5, P < .001), but remained smaller than in healthy individuals. The standard
      deviation increased by 0.46 degrees  per day between 14 and 38 days and tapered
      off to 0.05 degrees  per day between 38 and 189 days poststroke. CONCLUSIONS: Our
      results suggest that restitution of motor control by dissociation of shoulder and
      elbow movements occurs mainly early poststroke. However, compared with healthy
      adults, most patients did not achieve fully dissociated upper limb movements at
      26 weeks poststroke, suggesting that upper limb motor control after stroke
      remains adaptive.

PMID- 23884016
TI  - Use of intrathecal baclofen for treatment of severe spasticity in selected
      patients with motor neuron disease.
AB  - OBJECTIVE: To assess the safety and efficacy of intrathecal baclofen (ITB)
      therapy for severe spasticity in patients with upper-motor neuron predominant
      motor neuron disease (U-MND). METHODS: A total of 44 patients with U-MND were
      referred for discussion of ITB therapy. Baseline and outcomes data were extracted
      on 35 patients from a clinical spasticity registry at a tertiary referral center.
      Patients choosing to initiate ITB (n = 20) were compared with those choosing
      conservative therapy (n = 15). RESULTS: At baseline, lower average pain score in
      the non-ITB group was the only significant difference between the 2 groups. A
      significant reduction in pain scores, Modified Ashworth Scale (MAS), Spasm
      Frequency Scale, and requirement for oral spasticity medications was observed
      within the ITB group at early and late follow-up. Within the non-ITB group, there
      was a significant increase in MAS scores between baseline and late follow-up. A
      statistically significant difference favoring the ITB group was observed for
      change in MAS score (P < .0001), Numerical Rating Scale pain score (P = .04),
      dose of oral baclofen (P = .002) and tizanidine (P = .003), and number of oral
      medications for spasticity (P = .002). There was no difference between the 2
      groups in the progression of hip flexor weakness or in the proportion of patients
      who became nonambulatory. CONCLUSIONS: Our findings suggest that ITB can
      effectively reduce spasticity and related symptoms without compromising function
      in selected patients with U-MND.

PMID- 23884017
TI  - Abdominal muscle training can enhance cough after spinal cord injury.
AB  - BACKGROUND: Respiratory complications in people with high-level spinal cord
      injury (SCI) are a major cause of morbidity and mortality, particularly because
      of a reduced ability to cough as a result of abdominal muscle paralysis.
      OBJECTIVE: . We investigated the effect of cough training combined with
      functional electrical stimulation (FES) over the abdominal muscles for 6 weeks to
      observe whether training could improve cough strength. METHODS: Fifteen SCI
      subjects (C4-T5) trained for 6 weeks, 5 days per week (5 sets of 10 coughs per
      day) in a randomized crossover design study. Subjects coughed voluntarily at the
      same time as a train of electrical stimulation was delivered over the abdominal
      muscles via posterolaterally positioned electrodes (50 Hz, 3 seconds).
      Measurements were made of esophageal (Pes) and gastric (Pga) expiratory pressures
      and the peak expiratory flow (PEFcough) produced at the 3 time points of before,
      during, and after the training. RESULTS: During voluntary coughs, FES cough
      stimulation improved Pga, Pes, and PEFcough acutely, 20-fold, 4-fold, and 50%,
      respectively. Six weeks of cough training significantly increased Pga (37.1 +/-
      2.0 to 46.5 +/- 2.9 cm H2O), Pes (35.4 +/- 2.7 to 48.1 +/- 2.9 cm H2O), and
      PEFcough (3.1 +/- 0.1 to 3.6 +/- 0.1 L/s). Cough training also improved pressures
      and flow during voluntary unstimulated coughs. CONCLUSIONS: FES of abdominal
      muscles acutely increases mechanical output in coughing in high-level SCI
      subjects. Six weeks of cough training further increases gastric and esophageal
      cough pressures and expiratory cough flow during stimulated cough maneuvers.

PMID- 23884019
TI  - Two homochiral organocatalytic metal organic materials with nanoscopic channels.
AB  - Two homochiral organocatalytic MOMs were prepared using tetra- and octa
      carboxylate ligands, respectively. The nanoscopic channels in these MOMs are
      lined by organonocatalytic chiral phosphoric acid derivatives of binol and ocMOM
      1 exhibited improved enantioselectivity over the parent ligand in the context of
      transfer hydrogenation of a series of benzoxazines. 

PMID- 23884018
TI  - Early intervention in the 3xTg-AD mice with an amyloid beta-antibody fragment
      ameliorates first hallmarks of Alzheimer disease.
AB  - The single-chain variable fragment, scFv-h3D6, has been shown to prevent in vitro
      toxicity induced by the amyloid beta (Abeta) peptide in neuroblastoma cell
      cultures by withdrawing Abeta oligomers from the amyloid pathway. Present study
      examined the in vivo effects of scFv-h3D6 in the triple-transgenic 3xTg-AD mouse
      model of Alzheimer disease. Prior to the treatment, five-month-old female
      animals, corresponding to early stages of the disease, showed the first
      behavioral and psychological symptoms of dementia -like behaviors. Cognitive
      deficits included long- and short-term learning and memory deficits and high
      swimming navigation speed. After a single intraperitoneal dose of scFv-h3D6, the
      swimming speed was reversed to normal levels and the learning and memory deficits
      were ameliorated. Brain tissues of these animals revealed a global decrease of
      Abeta oligomers in the cortex and olfactory bulb after treatment, but this was
      not seen in the hippocampus and cerebellum. In the untreated 3xTg-AD animals, we
      observed an increase of both apoJ and apoE concentrations in the cortex, as well
      as an increase of apoE in the hippocampus. Treatment significantly recovered the
      non-pathological levels of these apolipoproteins. Our results suggest that the
      benefit of scFv-h3D6 occurs at both behavioral and molecular levels. 

PMID- 23884020
TI  - Effects of treatment for anestrus in water buffaloes with PGF2alpha and GnRH in
      comparison with vitamin-mineral supplement, and some factors influencing
      treatment effects.
AB  - The effect of treatment for anestrus in buffaloes with a PGF2alpha or GnRH
      injection and vitamin-mineral (Vit-M) supplementation for 1 to 2 months and some
      factors influencing the treatment effect were studied. In anestrus buffaloes with
      CL, an injection of PGF2alpha tended to show higher estrus detection and
      pregnancy rates within 17 days after treatment than Vit-M supplementation
      (P<0.10). In those with inactive ovaries, effect of GnRH and Vit-M did not
      differ. Body condition score of the animals before treatment affected pregnancy
      rate within 17 days after treatment (P<0.05). Pregnancy rate within 4 months
      after treatment was adversely influenced by low serum concentrations of calcium
      (P<0.01) and gastrointestinal parasitic infection before treatment (P<0.05). 

PMID- 23884021
TI  - Successful resolution of esophageal granulomas in a dog infected with Spirocerca
      lupi.
AB  - A 13-year-old female Labrador Retriever presented with chronic regurgitation.
      Radiography and computed tomography (CT) revealed nodules in the caudal
      esophagus. Upper gastrointestinal endoscopy followed by histopathological
      examination revealed esophageal granulomas caused by Spirocerca lupi. The
      infection was treated with milbemycin oxime. The therapy was successful, and a
      remarkable reduction in granulomas was observed. This case report describes the
      diagnostic imaging findings and treatment outcome of a dog with S. lupi infection
      in Japan. 

PMID- 23884022
TI  - Detection of calprotectin and apoptotic activity in the colon of marmosets with
      chronic diarrhea.
AB  - The common marmoset (Callithrix jacchus) is used as a non-human primate
      laboratory animal. Marmoset wasting syndrome (MWS) is a disease endemic to
      captive colonies, and the pathogenesis is unclear. In the present study,
      marmosets with chronic bloody high-viscosity diarrhea, which is a contributing
      factor to MWS, were evaluated, and inflammation in the colon was found.
      Calprotectin is a surrogate marker of intestinal inflammation and induces
      apoptosis. Marmosets with chronic diarrhea exhibited higher levels of fecal
      calprotectin. Histochemical analyses showed high expression of calprotectin in
      the extravascular neutrophils and apoptosis in the chronic colitis lesions. No
      internal microbiological diseases were identified. Although the cause of chronic
      colitis was not identified, the marmoset could be a useful model of inflammatory
      bowel disease. 

PMID- 23884023
TI  - Dermal cell damage induced by topical application of non-steroidal anti
      inflammatory drugs is suppressed by trehalose co-lyophilization in ex vivo
      analysis.
AB  - Topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) is
      generally considered safer than oral administration, although the former can
      occasionally induce cutaneous irritation. We hypothesized that the cutaneous
      irritation by topical NSAIDs might be suppressed by trehalose, which has
      protective effects on biological membranes. Using the three-dimensional cultured
      human skin model, Living Skin Equivalent-high, we found that cutaneous damage due
      to NSAIDs was reduced by concomitant use of trehalose and that this effect of
      trehalose was reinforced by co-lyophilization of NSAIDs with trehalose. The anti
      inflammatory effect of co-lyophilized NSAIDs with trehalose was comparable to
      that seen with NSAIDs alone in a rat model. Our results suggest that co
      lyophilization of NSAIDs with trehalose might be a novel procedure that can help
      prevent NSAIDs-induced skin irritation. 

PMID- 23884024
TI  - Bradykinin and its role in osteoarthritis.
AB  - Osteoarthritis (OA), the most common joint disorder, is a disease involving all
      the articular structures. It presents both degenerative and inflammatory aspects.
      Recently, the important role of Bradykinin (BK), a phlogistic mediator, has been
      proposed in the pathophysiology of OA. In our review, we summarized the currently
      available information on the mechanisms of action of BK in OA by linking its B2
      receptors. Then, we analyzed the data about the effects of BK in synoviocytes and
      chondrocytes cultures. Furthermore, we described the action of B2 receptor
      antagonists (Icatibant and Fasitibant), presenting them as new promising symptom
      anddisease- modifying agents in the treatment of OA. However, more in vitro,
      animal model and clinical studies, are needed to better understand the mechanisms
      of action as well as the efficacy and tolerability of the B2 receptor antagonists
      in OA. 

PMID- 23884025
TI  - Assessment of subclinical atherosclerosis in ankylosing spondylitis: correlations
      with disease activity indices.
AB  - The aim of the study was to evaluate atherosclerosis in ankylosing spondylitis
      (AS) through the assessment of morphological and functional measures of
      subclinical atherosclerosis. Twenty patients [M/F=12/8, age (median/range)
      43.5/28-69 years; disease duration (median/range) 9.7/1-36) years] with AS
      classified according to modified New York criteria and twenty age and sex related
      healthy controls with negative past medical history for cardiovascular events
      were enrolled in the study. In all patients and controls, the intima-media
      thickness (IMT) of common carotid artery, carotid bulb and internal carotid
      artery, and the flow-mediated dilatation (FMD) of non-dominant arm brachial
      artery were determined, using a sonographic probe Esaote GPX (Genoa, Italy).
      Furthermore, we assess the main disease activity and disability indices [bath
      ankylosing spondylitis disease activity index, ankylosing spondylitis disease
      activity score-eritrosedimentation rate (ASDAS-ESR), ASDAS-C-reactive protein
      (CRP), bath ankylosing spondylitis metrology index, bath ankylosing spondylitis
      functional index) and acute phase reactants. Plasmatic values of total
      cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride and
      homocysteine were carried out in all twenty patients. IMT at carotid bulb was
      significant higher in patients than in controls (0.67 mm vs 0.54 mm; P=0.03). FMD
      did not statistically differ between patients and controls (12.5% vs 15%;
      P>0.05). We found a correlation between IMT at carotid bulb and ESR (rho 0.43;
      P=0.04). No correlation was found between FMD and disease activity and disability
      indices. This study showed that in AS patients, without risk factors for
      cardiovascular disease, carotid bulb IMT, morphological index of subclinical
      atherosclerosis, is higher than in controls. 

PMID- 23884026
TI  - Regional differences of vitamin D deficiency in rheumatoid arthritis patients in
      Italy.
AB  - Vitamin D deficiency is very common in patients with rheumatoid arthritis (RA).
      Aim of this study was to evaluate the prevalence of vitamin D deficiency among
      the different Italian regions and whether these variations are associated with
      different severity of the disease. The study includes 581 consecutive RA patients
      (464 women), not taking vitamin D supplements, from 22 Italian rheumatology
      centres uniformly distributed across Italy. Together with parameters of disease
      activity (disease activity score 28), functional impairment (activities of daily
      living and health assessment questionnaire disability index) and mean sun
      exposure time, all patients had serum 25-hydroxyvitamin D (25OHD) measured in a
      centralized laboratory. Vitamin D deficiency (25OHD level <20 ng/mL) was very
      frequent among RA patients; its prevalence was 60%, 52% and 38% in southern,
      central and northern Italy, respectively. Mean disease activity and disability
      scores were worse in southern regions of Italy. These scores were inversely
      related to 25OHD levels and this correlation remained statistically significant
      after adjusting for both body mass index (BMI) and sun exposure time. However,
      disease severity remained significantly higher in southern regions versus central
      northern Italy after adjustment also for serum 25OHD levels, age and BMI. In RA
      Italian patients there are significant regional differences in the prevalence of
      vitamin D deficiency explained by different BMI, and sun exposure time, and
      inversely associated with disease activity and disability scores. 

PMID- 23884027
TI  - Bone mineral density in women on long-term mud-bath therapy in a Salus per Aquam
      (SPA) environment.
AB  - The objective of this study was to assess bone mineral density (BMD) in women on
      long-term mud-bath therapy (MBT) for osteoarthritis in a Salus per Aquam (SPA)
      environment. Two hundred and fifty female patients were randomly enrolled in this
      study in the SPA center of Sardara (Cagliari, Italy) where they were treated with
      a combination of daily full body mudpacks and bicarbonate-alkaline mineral water
      baths at cycles of 2 weeks/year. BMD was evaluated by means of calcaneus
      ultrasonometry (Sahara Hologic Inc., Bedford, MA, USA) and results analyzed
      according to duration of treatment and clinical variables. In the group of
      patients undergoing MBT for more than 10 years (group A) and for 3 to 10 years
      (group B) a reduced frequency of osteopenia and osteoporosis was detected (35.8%
      and 7.6% group A; 38.4% and 8.5% group B, respectively) compared to controls
      (group C) (48.9% and 23.4%, P<0.01 and P<0.001). Furthermore, higher T-score
      values were detected in group A and B (-1.05+/-1.28 and -1.24+/-0.94,
      respectively) compared to group C (-1.93+/-0.78) (P<0.0002 and P<0.0001). Similar
      results were observed in the analysis of data restricted to women in menopause
      only. Long-term mud-bath therapy in SPA environment appeared to be beneficial for
      BMD. 

PMID- 23884028
TI  - Temporomandibular joint dysfunction in various rheumatic diseases.
AB  - Temporomandibular disorder (TMD) is an inclusive term in which those conditions
      disturbing the masticatory function are embraced. It has been estimated that 33%
      of the population have signs of TMD, but less than 5% of the population will
      require treatment. The objective of this study was to measure the frequency of
      TMD in rheumatoid arthritis (RA), osteoarthrosis (OA), ankylosing spondylitis
      (AS) and systemic lupus erythematosus, and to define the limitations in
      everyday's life that patients perceive when present. A six-month survey of
      consecutive outpatients in a rheumatology clinic in a teaching hospital in Mexico
      was carried out. We defined TMD as: 1) the presence of pain; 2) difficulty on
      mouth opening, chewing or speaking; 3) the presence of non-harmonic movements of
      the temporomaxilar joints. All three characteristics had to be present. Z test
      was used to define differences between proportions. We present the results of 171
      patients. Overall, 50 patients had TMD according to our operational definition
      (29.24%). Up to 76% of the sample had symptoms associated with the condition. TMD
      is more frequent in OA and in AS (29.24% vs 38% OA, P=0.009; 39% AS; P=0.005). We
      found no association between the severity of TMD and the request for specific
      attention for the discomfort produced by the condition. Only 8 of 50 (16%)
      patients with TMD had requested medical help for their symptoms, and they were
      not the most severe cases. TMD is more frequent in RA and OA. Although it may
      produce severe impairment, patients seem to adapt easily. 

PMID- 23884029
TI  - A case of propylthiouracil-induced antineutrophilic cytoplasmic antibody-positive
      vasculitis successfully treated with radioactive iodine.
AB  - Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis is one of the
      rare complications of propylthiouracil treatment. Having a variable clinical
      spectrum, it may be presented with both skin limited vasculitis and life
      threatening systemic vasculitis. In this study, we present a case that developed
      ANCA-positive vasculitis with skin and kidney involvement (hematuria and
      proteinuria) six months after propylthiouracil treatment was initiated for toxic
      nodular goiter. Proteinuria recovered dramatically subsequent to radioactive
      iodine treatment following ceasing the drug. 

PMID- 23884030
TI  - Rapid effectiveness of certolizumab pegol in non-radiographic axial
      spondyloarthritis.
AB  - In axial spondyloarthritis (SpA), the efficacy of certolizumab pegol (CZP), a
      novel pegylated anti-tumor necrosis factor alpha drug has not been investigated.
      We report that CZP showed a rapid effectiveness, assessed clinically and by
      magnetic resonance imaging, in a patient with a non-radiographic axial SpA,
      classified according to Assessment in SpondyloArthritis International Society
      (ASAS) criteria. This case suggests that CZP could be considered an useful
      treatment in non-radiographic axial SpA, supporting that an earlier therapeutic
      approach could play a relevant role in the management of the disease. 

PMID- 23884031
TI  - Diffuse alveolar hemorrhage as a manifestation of Behcet disease.
AB  - Diffuse alveolar hemorrhage (DAH) is a rare life-threatening condition which
      refers to the presence of red blood cells within alveoli deriving from hemorrhage
      originating in the pulmonary microvasculature. It differs from alveolar filling,
      in which blood cells derive from localized bleeding, usually of bronchial origin.
      DAH may be part of diffuse alveolar injury of any origin. DAH should be
      considered a medical emergency due to the significant morbidity and mortality
      associated with respiratory failure, when secondary to impaired oxygen uptake
      from alveoli filled with erythrocytes. Patients with alveolar hemorrhage present
      with non-specific symptoms like dyspnea, cough and hemoptysis, which is not
      always present. They may develop acutely or insidiously over a few days. We
      present a case of a patient with probable Behcet's disease complicated by
      pulmonary capillaritis and DAH resulting in refractory respiratory failure and
      death. 

PMID- 23884032
TI  - Radiotelemetric assessment of intracavernosal pressure in apomorphine-induced
      erection: hypercholesterolemic rats vs normal control.
AB  - A recording of the intracavernosal pressure (ICP) in conscious rats using
      telemetry has the advantage of being able to evaluate erection under
      physiological conditions. The aim of this study was to determine whether the
      radiotelemetric assessment of ICP in apomorphine-induced erection is appropriate
      for assessing erectile function in an animal model of disease. Seven rats were
      assigned to the normal group, and another nine rats were assigned to the
      hypercholesterolemia group. A telemetric pressure sensor was implanted in the
      corpus cavernosum. Pressure was recorded in freely moving animals after
      apomorphine injection. Sexual events were visually identified and recorded. Only
      the pressure increase occurring during sexual behavior was analyzed. The main
      outcome measures were as follows: latency for first peak after injection
      (latency), duration, maximum ICP (Max ICP) and area under the curve (AUC). The
      mean latency, mean duration of each episode, mean Max ICP, mean AUC and mean
      summed AUC were 389.9 +/- 59.4 s, 61.6 +/- 7.8 s, 140.0 +/- 22.5 mm Hg, 1834.4 +/
      358.2 mm Hg s and 3259.1 +/- 795.9 mm Hg s, respectively, for the normal group
      vs 652.8 +/- 102.2 s, 32.4 +/- 5.2 s, 92.7 +/- 6.4 mm Hg, 572.9 +/- 73.6 mm Hg s
      and 739.9 +/- 87.2 mm Hg s, respectively, for the hypercholesterolemia group.
      There was a significant difference in mean latency, mean AUC and mean summed AUC.
      Additionally, we cannot find any obvious immediate adverse events after surgical
      implantation in both normal control and hypercholesterolemic rats. And, no
      catheter displacement and no adverse local reaction, including fibrosis to the
      implant, were observed. In conclusion, radiotelemetric assessment of ICP in
      apomorphine-induced erection provided consistent and accurate data during
      erectile events, and was appropriate for assessing erectile function in an animal
      model of disease.

PMID- 23884033
TI  - Anti-neurofascin antibody in patients with combined central and peripheral
      demyelination.
AB  - OBJECTIVES: We aimed to identify the target antigens for combined central and
      peripheral demyelination (CCPD). METHODS: We screened target antigens by
      immunohistochemistry and immunoblotting using peripheral nerve tissues to
      identify target antigens recognized by serum antibodies from selected CCPD and
      chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then
      measured the level of antibody to the relevant antigen in 7 patients with CCPD,
      16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with
      Guillain-Barre syndrome, 21 patients with other neuropathies, and 23 healthy
      controls (HC) by ELISA and cell-based assays using HEK293 cells. RESULTS: At the
      initial screening, sera from 2 patients with CCPD showed cross-like binding to
      sciatic nerve sections at fixed intervals, with nearly perfect colocalization
      with neurofascin immunostaining at the node and paranode. ELISA with recombinant
      neurofascin revealed significantly higher mean optical density values in the CCPD
      group than in other disease groups and HC. Anti-neurofascin antibody positivity
      rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis,
      25% in patients with CIDP, 15% in patients with Guillain-Barre syndrome, and 0%
      in patients with other neuropathies and HC. The cell-based assay detected serum
      anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative.
      CSF samples examined from 2 patients with CCPD were both positive. In anti
      neurofascin antibody-positive CCPD patients, including those with a limited
      response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the
      symptoms. CONCLUSION: Anti-neurofascin antibody is frequently present in patients
      with CCPD. Recognition of this antibody may be important, because patients with
      CCPD who are antibody positive respond well to IV immunoglobulin or plasma
      exchange.

PMID- 23884034
TI  - Cardiovascular disease and spinal cord injury: results from a national population
      health survey.
AB  - OBJECTIVE: To evaluate the association between cardiovascular disease (CVD) and
      spinal cord injury (SCI) in a large representative sample. METHODS: Data were
      compiled from more than 60,000 individuals from the 2010 cycle of the cross
      sectional Canadian Community Health Survey (CCHS). Multivariable logistic
      regression analysis was conducted to examine this relationship, adjusting for
      confounders and using probability weighting to account for the CCHS sampling
      method. RESULTS: After adjusting for age and sex, SCI was associated with a
      significant increased odds of heart disease (adjusted odds ratio [OR] = 2.72, 95%
      confidence interval [CI] 1.94-3.82) and stroke (adjusted OR = 3.72, 95% CI 2.22
      6.23). CONCLUSIONS: These remarkably heightened odds highlight the exigent need
      for targeted interventions and prevention strategies addressing modifiable risk
      factors for CVD in individuals with SCI.

PMID- 23884035
TI  - Head drop in Huntington disease: insights into the pathophysiology.

PMID- 23884036
TI  - Subependymal mass lesions and peripheral polyneuropathy in adult-onset glutaric
      aciduria type I.
AB  - Glutaric aciduria type I (GA-I) is an autosomal recessive disease caused by a
      deficiency of the mitochondrial enzyme glutaryl CoA dehydrogenase (GCDH). This
      metabolic block causes increased urinary concentrations of glutaric and 3
      hydroxyglutaric acids. The accumulation and excretion of glutarylcarnitine esters
      leads to secondary carnitine deficiency. GA-I has an incidence of 1:30,000. The
      clinical hallmark of GA-I is an acute encephalopathic crisis, with bilateral
      striatal necrosis presented by severe dystonic dyskinetic disorder. Most patients
      have their first symptoms during infancy, but some have a less severe form of the
      disease and some may even remain asymptomatic.

PMID- 23884037
TI  - Discontinuation of statin therapy associates with Parkinson disease: a population
      based study.
AB  - OBJECTIVE: To evaluate the effect of discontinuing statin therapy on incidence of
      Parkinson disease (PD) in statin users. METHODS: Participants who were free of PD
      and initiated statin therapy were recruited between 2001 and 2008. We examined
      the association between discontinuing use of statins with different lipophilicity
      and the incidence of PD using the Cox regression model with time-varying statin
      use. RESULTS: Among the 43,810 statin initiators, the incidence rate for PD was
      1.68 and 3.52 per 1,000,000 person-days for lipophilic and hydrophilic statins,
      respectively. Continuation of lipophilic statins was associated with a decreased
      risk of PD (hazard ratio [HR] 0.42 [95% confidence interval 0.27-0.64]) as
      compared with statin discontinuation, which was not modified by comorbidities or
      medications. There was no association between hydrophilic statins and occurrence
      of PD. Among lipophilic statins, a significant association was observed for
      simvastatin (HR 0.23 [0.07-0.73]) and atorvastatin (HR 0.33 [0.17-0.65]),
      especially in female users (HR 0.11 [0.02-0.80] for simvastatin; HR 0.24 [0.09
      0.64] for atorvastatin). As for atorvastatin users, the beneficial effect was
      seen in the elderly subgroup (HR 0.42 [0.21-0.87]). However, long-term use of
      statins, either lipophilic or hydrophilic, was not significantly associated with
      PD in a dose/duration-response relation. CONCLUSIONS: Continuation of lipophilic
      statin therapy was associated with a decreased incidence of PD as compared to
      discontinuation in statin users, especially in subgroups of women and elderly.
      Long-term follow-up study is needed to clarify the potential beneficial role of
      lipophilic statins in PD.

PMID- 23884038
TI  - Glatiramer acetate-induced acute hepatotoxicity in an adolescent with MS.
AB  - Glatiramer acetate (GA), a synthetic copolymer, is a frequently used first-line
      treatment for relapsing-remitting multiple sclerosis (RRMS). Probable autoimmune
      hepatotoxicity during GA treatment has been reported,(1-4) but GA hepatotoxicity
      in the absence of positive autoimmune markers has not previously been described.
      Here, we report GA-induced hepatotoxicity in a pediatric patient with multiple
      sclerosis (MS). 

PMID- 23884039
TI  - Rating scales for musician's dystonia: the state of the art.
AB  - Musician's dystonia (MD) is a focal adult-onset dystonia most commonly involving
      the hand. It has much greater relative prevalence than non-musician's focal hand
      dystonias, exhibits task specificity at the level of specific musical passages,
      and is a particularly difficult form of dystonia to treat. For most MD patients,
      the diagnosis confirms the end of their music performance careers. Research on
      treatments and pathophysiology is contingent upon measures of motor function
      abnormalities. In this review, we comprehensively survey the literature to
      identify the rating scales used in MD and the distribution of their use. We also
      summarize the extent to which the scales have been evaluated for their clinical
      utility, including reliability, validity, sensitivity, specificity to MD, and
      practicality for a clinical setting. Out of 135 publications, almost half (62)
      included no quantitative measures of motor function. The remaining 73 studies
      used a variety of choices from among 10 major rating scales. Most used subjective
      scales involving either patient or clinician ratings. Only 25% (18) of the
      studies used objective scales. None of the scales has been completely and
      rigorously evaluated for clinical utility. Whether studies involved treatments or
      pathophysiologic assays, there was a heterogeneous choice of rating scales used
      with no clear standard. As a result, the collective interpretive value of those
      studies is limited because the results are confounded by measurement effects. We
      suggest that the development and widespread adoption of a new clinically useful
      rating scale is critical for accelerating basic and clinical research in MD. 

PMID- 23884040
TI  - Reversible cerebral vasoconstriction syndrome and cervical artery dissection in
      20 patients.
AB  - OBJECTIVES: To describe clinical-radiologic characteristics in a prospective
      series of patients having both confirmed reversible cerebral vasoconstriction
      syndrome (RCVS) and cervical artery dissection (CeAD). METHODS: From January 2004
      to December 2011, from our prospective cohorts of RCVS and CeAD, we studied
      patients with both conditions. RESULTS: Of 173 RCVS cases and 285 CeAD cases, 20
      patients (18 women, 2 men; mean age 41 years) had both RCVS and CeAD. Main
      associated conditions were migraine (12/20) and postpartum (5/18). Clinical
      features included severe headache in all patients, neck pain in 15, focal
      neurologic deficit in 9, and seizures in 4. Pain was the only symptom in 10
      patients. All patients had multifocal cerebral vasoconstriction. There were brain
      lesions in 12 patients, cortical subarachnoid hemorrhage in 11, posterior
      reversible encephalopathy syndrome in 4, intracerebral hemorrhage in 3, and
      infarcts in 4. CeAD involved one artery in 13 patients and multiple arteries in
      7. CeAD mostly affected vertebral arteries (25 of 30 CeAD). Only one vertebral
      CeAD was associated with a related symptomatic infarct. At 3 months, 18 patients
      had fully recovered, all patients showed reversal of cerebral vasoconstriction,
      and 21 dissected arteries had normalized, whereas 9 arteries showed residual
      stenosis (7) and/or aneurysm (3). CONCLUSION: The association of RCVS and CeAD
      was found in 12% of our patients with RCVS and 7% of our patients with CeAD.
      Underlying mechanisms are unknown. In practice, our results point to the need for
      a systematic study of both cervical and intracranial arteries in the 2
      conditions.

PMID- 23884041
TI  - Responsiveness to reduced dosage of rituximab in Chinese patients with
      neuromyelitis optica.
AB  - OBJECTIVE: To determine the effect of a lower dose of rituximab in depleting B
      lymphocytes, maintaining low B-cell counts, and relapse in patients with
      neuromyelitis optica (NMO) and NMO spectrum disorders. METHODS: We treated 5
      Chinese patients with deteriorating NMO and NMO spectrum disorders with a 100-mg
      IV infusion of rituximab once a week for 3 consecutive weeks, followed by
      additional infusion of the same dosage depending on circulating B-cell
      repopulation. RESULTS: This reduced dosage of rituximab was sufficient to deplete
      B cells and maintain low B-cell counts. None of the treated patients experienced
      relapse, and all patients exhibited stabilized or improved neurologic function
      during the 1-year follow-up period. MRI revealed the absence of new lesions, no
      enhancement in spinal cord and brain, a significant shrinkage of spinal cord
      segments, and a reduction/disappearance of previous brain lesions. CONCLUSION: A
      lower dosage of rituximab may be sufficient in depleting B cells, maintaining low
      B-cell counts, and preventing disease progression in Chinese patients with NMO.

PMID- 23884043
TI  - Holding on to statins in Parkinson disease.

PMID- 23884042
TI  - Impaired default network functional connectivity in autosomal dominant Alzheimer
      disease.
AB  - OBJECTIVE: To investigate default mode network (DMN) functional connectivity MRI
      (fcMRI) in a large cross-sectional cohort of subjects from families harboring
      pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor
      protein (APP) mutations participating in the Dominantly Inherited Alzheimer
      Network. METHODS: Eighty-three mutation carriers and 37 asymptomatic noncarriers
      from the same families underwent fMRI during resting state at 8 centers in the
      United States, United Kingdom, and Australia. Using group-independent component
      analysis, fcMRI was compared using mutation status and Clinical Dementia Rating
      to stratify groups, and related to each participant's estimated years from
      expected symptom onset (eYO). RESULTS: We observed significantly decreased DMN
      fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident
      in the precuneus/posterior cingulate and parietal cortices (p < 0.001).
      Comparison of asymptomatic mutation carriers with noncarriers demonstrated
      decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right
      parietal cortex (p = 0.0016). We observed a significant interaction between
      mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation
      carriers approached and surpassed their eYO. CONCLUSION: Functional disruption of
      the DMN occurs early in the course of autosomal dominant Alzheimer disease,
      beginning before clinically evident symptoms, and worsening with increased
      impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker
      across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a
      secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease.

PMID- 23884044
TI  - Link between cardiovascular disease and spinal cord injury: new evidence and
      update.

PMID- 23884045
TI  - C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic
      study.
AB  - OBJECTIVE: To determine the histopathologic bases for the observed incidence of
      parkinsonism in families with C9ORF72 expansions, which typically cause
      amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia. METHODS: DNA
      was extracted from 377 brains with the histopathologic diagnosis of idiopathic
      Parkinson disease or related disorders and analyzed for C9ORF72 expansions. alpha
      Synuclein and p62 immunohistochemistry of the substantia nigra (SN) was
      undertaken in brains of 17 ALS cases with (C9ORF72+) and 51 without (C9ORF72-)
      the C9ORF72 expansion. RESULTS: Only 1 of 338 cases with pathologically confirmed
      idiopathic Parkinson disease had a C9ORF72 expansion. Similarly, only 1 of 17
      C9ORF72+ brains displayed features suggestive of alpha-synucleinopathy. In
      contrast, p62-positive, TDP-43-negative neuronal cytoplasmic inclusions within
      the SN were considerably more frequent in C9ORF72+ brain tissue than in the
      C9ORF72- brains (p = 0.005). Furthermore, there was a more marked loss of
      dopaminergic neurons in the SN of C9ORF72+ ALS brains than C9ORF72- ALS brains (p
      = 0.029). CONCLUSIONS: SN involvement is common in C9ORF72+ ALS but can be
      clearly distinguished from Parkinson disease-related mechanisms by the presence
      of p62-positive inclusions and the absence of alpha-synuclein-positive Lewy
      bodies or Lewy neurites.

PMID- 23884046
TI  - A pilot study examining moral distress in nurses working in one United States
      burn center.
AB  - Moral distress is described as the painful feelings and psychological
      disequilibrium when a person believes she knows the morally right action to take
      and is unable to carry it out because of external or internal constraints. It has
      been studied in intensive care unit (ICU) nurses, but to the best of our
      knowledge not in burn ICU nurses. A pilot study was performed to gather initial
      data on moral distress among nurses treating burn victims. Findings from an
      intervention aimed at decreasing the level of moral distress in these nurses are
      reported. Nurses (n = 13) were recruited from one U.S. burn ICU and were
      randomized into two groups. A separate sample pretest post-test design was used.
      Group A completed the Moral Distress Scale-Revised (MDS-R) and Self-efficacy (SE)
      Scale before a 4-week educational intervention involving weekly 60-minute
      sessions, and Group B completed both scales afterward. Participants also
      completed written evaluations after each session. The MDS-R and SE Scale were
      readministered to both groups 6 weeks after the intervention was completed. Given
      the size and distribution of the sample, nonparametric data analyses were used.
      The MDS-R median score for Group B (92.0) was significantly different
      statistically from Group A (40.5) with P = .032 directly after the intervention
      was completed. No significant difference was found in the median SE scores
      between Group A (34.5) and Group B (34.0; P = .616). The median for Group B was
      69 and Group A was 60.5 (P = .775). At the 6-week follow up, the difference
      between the two groups was no longer observed. Defining and discussing moral
      distress may have contributed to increased awareness and higher levels of moral
      distress in Group B directly postintervention. The changes in moral distress
      levels postintervention and at the 6-week follow up highlight the need to examine
      the intervention in a larger sample. 

PMID- 23884047
TI  - Applying Quality Function Deployment Model in Burn Unit Service Improvement.
AB  - Quality function deployment (QFD) is one of the most effective quality design
      tools. This study applies QFD technique to improve the quality of the burn unit
      services in Ghotbedin Hospital in Shiraz, Iran. First, the patients' expectations
      of burn unit services and their priorities were determined through Delphi method.
      Thereafter, burn unit service specifications were determined through Delphi
      method. Further, the relationships between the patients' expectations and service
      specifications and also the relationships between service specifications were
      determined through an expert group's opinion. Last, the final importance scores
      of service specifications were calculated through simple additive weighting
      method. The findings show that burn unit patients have 40 expectations in six
      different areas. These expectations are in 16 priority levels. Burn units also
      have 45 service specifications in six different areas. There are four-level
      relationships between the patients' expectations and service specifications and
      four-level relationships between service specifications. The most important burn
      unit service specifications have been identified in this study. The QFD model
      developed in the study can be a general guideline for QFD planners and
      executives.

PMID- 23884051
TI  - Immunotherapy to treat leukemia possibly ineffective for advanced disease.

PMID- 23884048
TI  - Clinical impact of sample interference on intensive insulin therapy in severely
      burned patients: a pilot study.
AB  - Severely burned patients benefit from intensive insulin therapy (IIT) for tight
      glycemic control (TGC). The authors evaluated the clinical impact of automatic
      correction of hematocrit and ascorbic acid interference for bedside glucose
      monitoring performance in critically ill burn patients. The performance of two
      point-of-care glucose monitoring systems (GMSs): 1) GMS1, an autocorrecting
      device, and 2) GMS2, a noncorrecting device were compared. Sixty remnant arterial
      blood samples were collected in a prospective observational study to evaluate
      hematocrit and ascorbic acid effects on GMS1 vs GMS2 accuracy paired against a
      plasma glucose reference. Next, we enrolled 12 patients in a pilot randomized
      controlled trial. Patients were randomized 1:1 to receive IIT targeting a TGC
      interval of 111 to 151 mg/dl and guided by either GMS1 or GMS2. GMS bias, mean
      insulin rate, and glycemic variability were calculated. In the prospective study,
      GMS1 results were similar to plasma glucose results (mean bias, -0.75 [4.0]
      mg/dl; n = 60; P = .214). GMS2 results significantly differed from paired plasma
      glucose results (mean bias, -5.66 [18.7] mg/dl; n = 60; P = .048). Ascorbic acid
      therapy elicited significant GMS2 performance bias (29.2 [27.2]; P < .001).
      Randomized controlled trial results reported lower mean bias (P < .001), glycemic
      variability (P < .05), mean insulin rate (P < .001), and frequency of
      hypoglycemia (P < .001) in the GMS1 group than in the GMS2 group. Anemia and high
      dose ascorbic acid therapy negatively impact GMS accuracy and TGC in burn
      patients. Automatic correction of confounding factors improves glycemic control.
      Further studies are warranted to determine outcomes associated with accurate
      glucose monitoring during IIT. 

PMID- 23884052
TI  - Overhaul of NCI Clinical Trial System Still in Progress.

PMID- 23884053
TI  - Impact of brisk walking on perceived health evaluated by a novel short
      questionnaire in sedentary and moderately obese postmenopausal women.
AB  - OBJECTIVE: The first objective of this study was to evaluate the impact of brisk
      walking on moderately obese (body mass index, 29-35 kg/m) postmenopausal women's
      perceived health, assessed through a novel short perceived health questionnaire
      (SPHQ), and to verify whether improvements in six items examined were related to
      cardiorespiratory fitness (CRF) and/or fat mass changes (study 1). The second
      objective of this study was to test the SPHQ against validated generic
      instruments (study 2). METHODS: From the 270 women included in study 1, 181
      participants were subjected to three 45-minute walking sessions per week at 60%
      of their heart rate reserve, whereas 58 women remained inactive for 4 months.
      Perceived health assessed through the SPHQ, body composition, and CRF were
      determined before and after the 4-month study period. Another sample of 20 women
      was selected to validate the SPHQ (study 2). RESULTS: Despite a lack of between
      group differences in the amelioration of four perceived health items, ideal
      weight and stress level were improved in women subjected to our walking program
      exclusively (P < 0.0001). Improved perceived healthy balanced diet was positively
      correlated to fat mass reduction in the walking group (r = 0.15; P < 0.05) only
      (study 1). The SPHQ shows good reproducibility for five of six items (intraclass
      correlation coefficients ranging from 0.77 to 0.89; P < 0.0001), and three of
      them were validated against generic tools (0.45 < r < 0.54; P < 0.05; study 2).
      CONCLUSIONS: Additional studies are needed to more accurately determine the
      relationships between changes in perceived health and changes in body fatness
      and/or CRF after endurance training and to continue the validation of the SPHQ.

PMID- 23884054
TI  - Significance of bladder trabeculation in postmenopausal women with severe pelvic
      organ prolapse: clinical and urodynamic assessments.
AB  - OBJECTIVE: Bladder trabeculation (BT) is a secondary result of bladder outlet
      obstruction (BOO), which may result from severe pelvic organ prolapse (POP) and
      cause lower urinary tract symptoms (LUTS). This study was conducted to
      investigate the relationship among clinical manifestations, urodynamic findings,
      and BT in women with severe POP. METHODS: We reviewed the medical records of
      patients with stage 3 or stage 4 POP who underwent prolapse surgical operation in
      a tertiary hospital between 2005 and 2011. All patients received preoperative
      evaluations, including urodynamic studies, cystoscopy, and a structured
      urogynecological questionnaire. Demographics, LUTS, pelvic floor symptoms, and
      urodynamic findings were compared between women with BT and women without BT.
      RESULTS: Of the 308 women included, 54.9% had BT and 12.7% were diagnosed with
      BOO (maximal flow rate <12 mL/s; detrusor pressure at maximal flow >20 cm H2O).
      Mean age, prevalence of urgency, urge incontinence, voiding difficulty, detrusor
      overactivity, and postvoid residual greater than 100 mL were significantly higher
      in women with BT than in women without BT. In addition, severe BT had
      significantly higher prevalences of detrusor overactivity, BOO, lower maximal
      cystometric capacity, urge incontinence, and anterior vaginal prolapse. Logistic
      regression demonstrated that detrusor overactivity was the only variable
      associated with BT. CONCLUSIONS: More than half of the women with severe POP have
      BT, which, when compared with women without BT, indicates higher incidences of
      LUTS, detrusor overactivity, and urinary retention. An objective evaluation of BT
      should become a prerequisite examination for women with severe POP who would
      undergo prolapse surgical operation.

PMID- 23884055
TI  - Resveratrol attenuated smokeless tobacco-induced vascular and metabolic
      complications in ovariectomized rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of smokeless tobacco
      extract on ovariectomized female rats and to investigate the role of resveratrol
      in alleviating associated vascular and diabetic complications. METHODS: Thirty
      six female Wistar rats (8 wk old) were subjected to bilateral ovariectomy (OVX)
      or sham operation and randomly assigned to six groups: sham operation; OVX; OVX +
      aqueous extract of smokeless tobacco (AEST); OVX + AEST + 17beta-estradiol; OVX +
      AEST + resveratrol 25 mg/kg/day PO; and OVX + AEST + resveratrol 50 mg/kg/day PO.
      All treatments were given for 60 days. Various vascular and metabolic markers
      (such as serum glucose, triglycerides, cholesterol, insulin, estradiol,
      glycosylated hemoglobin, glucose tolerance), ex vivo vascular reactivity of
      aortic ring, and aortic collagen levels were estimated after the treatments.
      RESULTS: Oral exposure to smokeless tobacco extract in ovariectomized female rats
      triggered a significant increase in metabolic markers (viz, serum triglycerides,
      cholesterol, glucose, insulin, glycosylated hemoglobin), and aortic collagen
      levels. It also led to decreased serum nitrate-nitrite levels and vascular
      reactivity. Resveratrol 50 mg/kg/day PO attenuated detrimental changes in aortic
      reactivity and aortic collagen levels, improved glucose tolerance, and reversed
      the deleterious effects on other serum parameters comparable to 17beta-estradiol.
      CONCLUSIONS: Resveratrol treatment for 60 days abrogates the deleterious effects
      of smokeless tobacco on ovariectomized female rats. Resveratrol in adequate doses
      can be effectively used as an alternative to estrogen therapy for smokeless
      tobacco-induced vascular and diabetic complications.

PMID- 23884057
TI  - Hepatitis C virus reinfection following treatment among people who use drugs.
AB  - Most new cases of hepatitis C virus (HCV) infections in the developed world are
      associated with injection drug use. However, treatment for people who inject
      drugs (PWID) is controversial, as successful treatment risks being followed by
      new infection. Reinfection after sustained virologic response has been reported,
      but is the risk so great that treatment should be withheld from this large HCV
      population? Preliminary evidence suggests that the reinfection incidence is low,
      but studies to date have been limited by small sample size and few cases of
      reinfection. In this review, we assess data from studies among PWID of HCV
      reinfection following treatment to give a reasonable estimate on how frequently
      reinfection appears and try to characterize those most at risk, The observation
      that spontaneous clearance of HCV reinfection following treatment occurs is
      suggestive of a partial protective immunity against persistent infection. 

PMID- 23884058
TI  - Management of mental health problems prior to and during treatment of hepatitis C
      virus infection in patients with drug addiction.
AB  - Psychiatric comorbidity is a common problem in patients with substance use
      disorders. Patients with psychiatric diseases and/or substance abuse have an
      increased risk for hepatitis C virus (HCV) infection. Furthermore, psychiatric
      problems occur frequently during antiviral treatment and may be associated with
      the use of interferon alpha (IFN-alpha) but also with the primary psychiatric
      condition. As a consequence, substance abuse and/or acute psychiatric problems
      are still important reasons for nontreatment of chronic HCV infection. However,
      prospective and controlled data from recent years showed that if an
      interdisciplinary treatment is provided, patients with substance use disorders
      and/or psychiatric diseases do not differ regarding sustained virologic response
      or IFN-alpha-associated complications such as depression when compared with
      controls. Moreover, depression as the most important acute IFN-alpha-associated
      psychiatric adverse event can be acutely treated or even prevented by
      antidepressant pretreatment. Other, more rare but severe complications such as
      mania, psychotic symptoms, or delirium need individual psychiatric interventions.

PMID- 23884059
TI  - Management of hepatitis C virus/HIV coinfection among people who use drugs in the
      era of direct-acting antiviral-based therapy.
AB  - Where active antiretroviral therapy (ART) is accessible, human immunodeficiency
      virus (HIV) is a survivable illness and effective ART can reduce HIV
      transmission. Chronic hepatitis C virus (HCV) has emerged as a threat to the
      survival of individuals harboring both HCV and HIV, due to high prevalence and
      aggressive disease course. The HCV/HIV coinfection epidemic has been driven by
      people who inject drugs (PWID), although incident HCV is rising among HIV
      infected men who have sex with men in the absence of drug injection. Coinfected
      individuals warrant aggressive treatment of both viruses; although early ART
      initiation is recommended to reduce the rate of liver disease progression, the
      most effective way to decrease HCV-related morbidity and mortality in coinfection
      is to achieve HCV viral eradication. Direct-acting antiviral (DAA) agents will
      soon revolutionize HCV treatment. Clinical data are needed regarding the efficacy
      of DAAs in coinfected PWID. Drug-drug interaction studies between ART, DAAs, and
      opiate substitution therapy must be expedited. Coinfected PWID should have
      equitable and universal access to HIV/AIDS, HCV, and addiction prevention, care,
      and treatment. Essential basic steps include improving screening for both
      infections and engaging coinfected PWID in HIV and HCV care early after
      diagnoses. Developing strategies to expand access to HCV therapy for coinfected
      PWID is imperative to stem the HCV epidemic and limit the morbidity and mortality
      of those at greatest risk for HCV disease progression. The ultimate goal must be
      the elimination of HCV from all coinfected PWID. 

PMID- 23884060
TI  - Drug-drug interactions in the treatment of HCV among people who inject drugs.
AB  - Boceprevir and telaprevir are inhibitors and substrates of the cytochrome P450
      3A4 family. With the use of these HCV protease inhibitors as part of standard
      therapy for chronic hepatitis C genotype 1 infection, drug-drug interactions with
      multiple medications being inductors, inhibitors, or substrates of cytochrome
      P450 3A4 can be expected. Due to the complexity of these interactions, predicting
      the expected magnitude and sometimes even the direction of the effect has proven
      to be difficult. Pharmacokinetic studies should be carried out to evaluate drugs
      with clinical relevance and possible interactions. This review focuses on the
      data available regarding drugs that are frequently used in the setting of
      addiction or used by patients with addiction. In addition to highlighting
      relevant drug-drug interactions, alternative drugs that can be safely used are
      suggested. 

PMID- 23884061
TI  - Recommendations for the management of hepatitis C virus infection among people
      who inject drugs.
AB  - In the developed world, the majority of new and existing hepatitis C virus (HCV)
      infections occur among people who inject drugs (PWID). The burden of HCV-related
      liver disease in this group is increasing, but treatment uptake among PWID
      remains low. Among PWID, there are a number of barriers to care that should be
      considered and systematically addressed, but these barriers should not exclude
      PWID from HCV treatment. Furthermore, it has been clearly demonstrated that HCV
      treatment is safe and effective across a broad range of multidisciplinary
      healthcare settings. Given the burden of HCV-related disease among PWID,
      strategies to enhance HCV assessment and treatment in this group are urgently
      needed. These recommendations demonstrate that treatment among PWID is feasible
      and provides a framework for HCV assessment, management, and treatment. Further
      research is needed to evaluate strategies to enhance assessment, adherence, and
      SVR among PWID, particularly as new treatments for HCV infection become
      available. 

PMID- 23884062
TI  - Moving the agenda forward: the prevention and management of hepatitis C virus
      infection among people who inject drugs.

PMID- 23884063
TI  - Injection drug use and hepatitis C virus infection in young adult injectors:
      using evidence to inform comprehensive prevention.
AB  - The hepatitis C virus (HCV) virus epidemic is ongoing in the United States and
      globally. Incidence rates remain high, especially in young adult injection drug
      users. New outbreaks of HCV in the United States among young adults, in
      predominantly suburban and rural areas, have emerged and may be fueling an
      increase in HCV. This paper discusses some key HCV prevention strategies that to
      date have not been widely researched or implemented, and wherein future HCV
      prevention efforts may be focused: (1) reducing sharing of drug preparation
      equipment; (2) HCV screening, and testing and counseling; (3) risk reduction
      within injecting relationships; (4) injection cessation and "breaks"; (5) scaled
      up needle/syringe distribution, HCV treatment, and vaccines, according to
      suggestions from mathematical models; and (6) "combination prevention." With
      ongoing and expanding transmission of HCV, there is little doubt that there is a
      need for implementing what is in the prevention "toolbox" as well as adding to
      it. Strong advocacy and resources are needed to overcome challenges to providing
      the multiple and comprehensive programs that could reduce HCV transmission and
      associated burden of disease worldwide in people who inject drugs. 

PMID- 23884064
TI  - Combination interventions to prevent HCV transmission among people who inject
      drugs: modeling the impact of antiviral treatment, needle and syringe programs,
      and opiate substitution therapy.
AB  - BACKGROUND: Interventions such as opiate substitution therapy (OST) and high
      coverage needle and syringe programs (HCNSP) cannot substantially reduce
      hepatitis C virus (HCV) prevalence among people who inject drugs (PWID). HCV
      antiviral treatment may prevent onward transmission. We project the impact of
      combining OST, HCNSP, and antiviral treatment on HCV prevalence/incidence among
      PWID. METHODS: An HCV transmission model among PWID was used to project the
      combinations of OST, HCNSP, and antiviral treatment required to achieve different
      prevalence and incidence reductions within 10 years for 3 chronic prevalence
      scenarios and the impact of HCV treatment if only delivered through OST programs.
      Multivariate and univariate sensitivity analyses were performed. RESULTS: Large
      reductions (>45%) in HCV chronic prevalence over 10 years require HCV antiviral
      treatment. Scaling up OST and HCNSP substantially reduces the treatment rate
      required to achieve specific HCV prevalence reductions. If OST and HCNSP coverage
      were increased to 40% each (no coverage at baseline), then annually treating 10,
      23, or 42 per 1000 PWID over 10 years would halve prevalence for 20%, 40%, or 60%
      baseline chronic HCV prevalences, respectively. Approximately 30% fewer
      treatments are necessary with new direct-acting antivirals. If coverage of OST
      and HCNSP is 50% at baseline, similar prevalence reductions require higher
      treatment rates for the same OST and HCNSP coverage. CONCLUSIONS: Combining
      antiviral treatment with OST with HCNSP is critical for achieving substantial
      reductions (>50%) in HCV chronic prevalence over 10 years. Empirical studies are
      required on how best to scale up antiviral treatment and combine treatment with
      other interventions.

PMID- 23884066
TI  - Understanding barriers to hepatitis C virus care and stigmatization from a social
      perspective.
AB  - A large body of literature emphasizes the relationship between stigma and adverse
      health outcomes and health access measures. For people living with hepatitis C
      virus (HCV), stigma is a defining feature given the association of HCV with the
      socially demonized practice of injection drug use. However, there is little
      literature that specifically examines stigma as a barrier to HCV care and
      treatment. This review argues that the relationship between the person living
      with HCV and their health worker can work to ameliorate the effects of stigma. We
      draw on an emerging literature that examines the positive association between a
      patient's "trust" in their health worker and outcomes such as increased
      healthcare utilization and reduced risk behaviors. We investigate a growing body
      of health services research that acknowledges the importance of stigma and
      demonstrates ways to build positive, enabling relationships between patient,
      health worker, and health setting. 

PMID- 23884065
TI  - Hepatitis C virus vaccines among people who inject drugs.
AB  - Most people who inject drugs (PWID) are infected with hepatitis C virus (HCV),
      and PWID have the highest risk of HCV infection of any risk group. The incidence
      of HCV infection is 5%-25% per year, demonstrating continued need for HCV
      infection prevention in PWID. Existing data in chimpanzees and PWID suggest that
      protective immunity against persistent HCV infection is achievable. Due to the
      high incidence of infection, PWID are both the most likely to benefit from a
      vaccine and a population in which vaccine efficacy could be tested. Challenges to
      testing a vaccine in PWID are significant. However, the first HCV vaccine trial
      in at-risk HCV-uninfected PWID was initiated in 2012. The results will likely
      guide future vaccine development and strategies for vaccination of this and other
      high-risk populations. 

PMID- 23884067
TI  - Models of care for the management of hepatitis C virus among people who inject
      drugs: one size does not fit all.
AB  - One of the major obstacles to hepatitis C virus (HCV) care in people who inject
      drugs (PWID) is the lack of treatment settings that are suitably adapted for the
      needs of this vulnerable population. Nevertheless, HCV treatment has been
      delivered successfully to PWID through various multidisciplinary models such as
      community-based clinics, substance abuse treatment clinics, and specialized
      hospital-based clinics. Models may be integrated in primary care--all under one
      roof in either addiction care units or general practitioner-based models--or can
      occur in secondary or tertiary care settings. Additional innovative models
      include directly observed therapy and peer-based models. A high level of
      acceptance of the individual life circumstances of PWID rather than rigid
      exclusion criteria will determine the level of success of any model of HCV
      management. The impact of highly potent and well-tolerated interferon-free HCV
      treatment regimens will remain negligible as long as access to therapy cannot be
      expanded to the most affected risk groups.

PMID- 23884069
TI  - Enhancing assessment and treatment of hepatitis C in the custodial setting.
AB  - Acute and chronic hepatitis C (HCV) infections are prevalent in custodial
      settings worldwide, yet provision of antiviral therapies is uncommon. This
      disparity between the burden of disease and hepatitis service delivery reflects
      the marginalized patient population, which features high rates of injection drug
      use and poor mental health. In addition, the prison environment is intended for
      deprivation of liberty and not healthcare. Screening for HCV infections is
      provided in most jurisdictions, but uptake rates remain low. Assessment and
      treatment of inmates is often provided only by community-based services. Despite
      these challenges, assessment and treatment of inmates with chronic HCV via prison
      based services has been shown to be feasible and effective. These services offer
      the potential to substantively increase HCV treatment uptake and reduce the
      burden of disease for the community at large. Improvements in the efficacy of HCV
      therapies via direct-acting antivirals, which also offer reduced treatment
      duration and decreased toxicities, mean that prison health services will be well
      placed for the treatment of large numbers of people with HCV who do not access
      health services in the community. 

PMID- 23884068
TI  - Assessment and treatment of hepatitis C virus infection among people who inject
      drugs in the opioid substitution setting: ETHOS study.
AB  - BACKGROUND: Access to hepatitis C virus (HCV) treatment remains extremely limited
      among people who inject drugs (PWID). HCV assessment and treatment was evaluated
      through an innovative model for the provision of HCV care among PWID with chronic
      HCV infection. METHODS: Enhancing Treatment for Hepatitis C in Opioid
      Substitution Settings (ETHOS) was a prospective observational cohort. Recruitment
      was through 5 opioid substitution treatment (OST) clinics, 2 community health
      centers, and 1 Aboriginal community controlled health organization in New South
      Wales, Australia. RESULTS: Among 387 enrolled participants, mean age was 41
      years, 71% were male, and 15% were of Aboriginal ethnicity. Specialist assessment
      was undertaken in 191 (49%) participants, and 84 (22%) commenced interferon-based
      treatment. In adjusted analysis, HCV specialist assessment was associated with
      non-Aboriginal ethnicity (adjusted odds ratio [AOR], 4.02; 95% confidence
      interval [CI], 2.05-7.90), no recent benzodiazepine use (AOR, 2.06; 95% CI, 1.31
      3.24), and non-1 HCV genotype (AOR, 2.13; 95% CI, 1.32-3.43). In adjusted
      analysis, HCV treatment was associated with non-Aboriginal ethnicity (AOR, 4.59;
      95% CI, 1.49-14.12), living with the support of family and/or friends (AOR, 2.15;
      95% CI, 1.25-3.71), never receiving OST (AOR, 4.40; 95% CI, 2.27-8.54), no recent
      methamphetamine use (AOR, 2.26; 95% CI, 1.12-4.57), and non-1 HCV genotype (AOR,
      3.07; 95% CI, 1.67-5.64). CONCLUSIONS: HCV treatment uptake was relatively high
      among this highly marginalized population of PWID. Potentially modifiable factors
      associated with treatment include drug use and social support.

PMID- 23884070
TI  - Peer support models for people with a history of injecting drug use undertaking
      assessment and treatment for hepatitis C virus infection.
AB  - People who inject drugs (PWID) are the group most affected by HCV; however,
      treatment uptake has been low. Engagement between PWID and healthcare workers has
      been characterized by mistrust and discrimination. Peer support for HCV is one
      way to overcome these barriers. Peer support models for chronic disease
      management have been successfully applied for other diseases. HCV peer support
      models have been implemented in various settings, but those that include opioid
      substitution treatment have been more common. Most models have been either
      service generated (provider led) or community controlled (peer led). Peer support
      models have been implemented successfully, with a range of outcomes including
      increased treatment knowledge and uptake and improved service provision. Genuine
      partnerships between peers and services were common across models and led to
      positive transformations for both clients and services. Further investigation of
      peer support for HCV treatment and its impact on both individuals and services is
      recommended. 

PMID- 23884071
TI  - Treatment of hepatitis C virus infection among people who are actively injecting
      drugs: a systematic review and meta-analysis.
AB  - BACKGROUND: Although guidelines recommend that people who inject drugs (PWID)
      should not be excluded from hepatitis C (HCV) treatment, some services remain
      reluctant to treat PWID. The aim of this review was to investigate sustained
      virologic response (SVR), adherence, discontinuation, and HCV reinfection among
      PWID. METHODS: A search of Medline, Embase, and Cochrane databases (between 2002
      and January 2012) was conducted for primary articles/conference abstracts
      examining HCV treatment outcomes in PWID. Meta-analysis was used to obtain pooled
      estimates of SVR, adherence, discontinuation, and HCV reinfection. RESULTS: Ten
      primary articles and 1 conference abstract met the inclusion criteria. Across 6
      studies (comprising 314 drug users, of whom 141 [45%] were PWID), pooled SVR was
      56% (95% confidence interval [CI], 50%-61%) for all genotypes, 37% (95% CI, 26%
      48%) for genotypes 1/4, and 67% (95% CI, 56%-78%) for genotypes 2/3. Pooled
      80/80/80 adherence was 82% (95% CI, 74%-89%) across 2 studies, and pooled
      treatment discontinuation was 22% (95% CI, 16%-27%) across 4 studies. Across 5
      studies (comprising 131 drug users) examining reinfection, pooled risk was 2.4
      (95% CI, .9-6.1) per 100 person-years. CONCLUSIONS: HCV treatment outcomes are
      acceptable in PWID, supporting treatment guidelines. The pooled estimate of HCV
      reinfection risk was low, but there was considerable uncertainty around this
      estimate. Further studies on the risk of reinfection are needed to assess the
      long-term effectiveness of HCV treatment in PWID.

PMID- 23884072
TI  - Directly observed pegylated interferon plus self-administered ribavirin for the
      treatment of hepatitis C virus infection in people actively using drugs: a
      randomized controlled trial.
AB  - BACKGROUND: This study investigated the efficacy and safety of directly observed
      pegylated interferon (peg-IFN) alfa-2a plus self-administered ribavirin (RBV) for
      the treatment of hepatitis C virus (HCV) among people with active drug use.
      METHODS: A randomized, open-label, parallel group trial of immediate vs delayed
      treatment with peg-IFN alfa-2a plus RBV in participants with recent injection
      drug and/or crack cocaine use (prior 3 months). The primary end point was
      sustained virologic response (SVR). RESULTS: Sixty-six participants were
      randomized (immediate treatment, n = 48; delayed treatment, n = 18). Loss to
      follow-up was comparable among those randomized to immediate and delayed
      treatment (23% vs 33%, P = .389). In a post hoc intent-to-treat analysis of all
      randomized individuals, the SVR was 65% (95% confidence interval [CI], 49%-78%;
      31/48) in those randomized to immediate treatment as compared to 39% (95% CI, 17%
      64%; 7/18) in those randomized to delayed treatment (P = .060). Among those who
      received delayed treatment (12/18), SVR was 58% (7/12). Among 60 participants who
      received at least 1 dose of study medication, SVR was 63% (95% CI, 50%-75%, n =
      38). Recent drug use at baseline (past month) did not impact completion or SVR.
      Discontinuation due to adverse events occurred in 7%. The HCV reinfection rate
      was 2.8 per 100 person-years (95% CI, 0.0-14.5 person-years) with 1 reinfection
      observed among 23 remaining in follow-up post-SVR (median, 1.8 years; range, 0.5
      1.8 years). CONCLUSIONS: Among people actively using drugs treated with directly
      observed peg-IFN alfa-2a plus self-administered RBV, SVR is comparable to that
      seen in clinical trials of non-drug users, and the rate of HCV reinfection is
      low.

PMID- 23884073
TI  - Psychoeducation improves hepatitis C virus treatment during opioid substitution
      therapy: a controlled, prospective multicenter trial.
AB  - BACKGROUND: People who inject drugs (PWID) have a high prevalence of hepatitis C
      virus (HCV) infection. However, PWID are considered "difficult to treat,"
      requiring a specifically adapted treatment setting, including psychosocial
      support. METHODS: In this prospective, German trial, the impact of
      psychoeducation (PE) on retention and sustained virologic response (SVR) during
      HCV therapy among PWID was evaluated. We included 198 patients in opiate
      substitution therapy, who fulfilled indications for antiviral treatment. All
      patients received pegylated interferon alfa-2a and ribavirin therapy. Patients in
      the intervention group (n = 82) received manualized PE sessions. RESULTS: In
      patients with HCV genotype 1 or 4 (GT 1/4), PE was associated with increased
      treatment completion (76% vs 55%, P = .038), whereas PE had no such effect among
      GT 2/3 patients, who showed fewer dropouts and higher SVR rates. Among GT 1/4
      patients, a minimum of 5 PE sessions was associated with increased SVR (71% vs
      48%, P = .037). Multivariate regression analyses confirmed the impact of PE in GT
      1/4 and revealed further predictors for retention and SVR, such as preexisting
      mental distress and adverse events. CONCLUSIONS: In patients with a higher risk
      of dropout due to GT 1/4 or mental distress, PE was shown to improve retention
      and SVR. PE is an effective supportive intervention for HCV therapy among PWID.

PMID- 23884074
TI  - Multilayered nano-prism vertex tips for tip-enhanced Raman spectroscopy and
      imaging.
AB  - We presented a scalable fabrication method for the preparation of multilayered
      nano-prism vertex (NV)-tips whose dimensions can be controlled for tip-enhanced
      Raman spectroscopy (TERS). The NV-tip had sharp vertices (diameter ~20 nm)
      originated from the chemical lift-off process after the angle-grinding process,
      enabling high resolution imaging. TERS measurements were performed on brilliant
      cresyl blue (BCB) molecules using a Ag/Au NV-tip, revealing the enhanced field
      localization at the vertices of the NV-tip. Furthermore, we could observe the
      polarization effect of the NV-tip. Our NV-tips should be a powerful tool for
      basic research on TERS experiments and SPM applications.

PMID- 23884075
TI  - Blast-related traumatic brain injury.
AB  - A bomb blast may cause the full severity range of traumatic brain injury (TBI),
      from mild concussion to severe, penetrating injury. The pathophysiology of blast
      related TBI is distinctive, with injury magnitude dependent on several factors,
      including blast energy and distance from the blast epicentre. The prevalence of
      blast-related mild TBI in modern war zones has varied widely, but detection is
      optimised by battlefield assessment of concussion and follow-up screening of all
      personnel with potential concussive events. There is substantial overlap between
      post-concussive syndrome and post-traumatic stress disorder, and blast-related
      mild TBI seems to increase the risk of post-traumatic stress disorder. Post
      concussive syndrome, post-traumatic stress disorder, and chronic pain are a
      clinical triad in this patient group. Persistent impairment after blast-related
      mild TBI might be largely attributable to psychological factors, although a
      causative link between repeated mild TBIs caused by blasts and chronic traumatic
      encephalopathy has not been established. The application of advanced neuroimaging
      and the identification of specific molecular biomarkers in serum for diagnosis
      and prognosis are rapidly advancing, and might help to further categorise these
      injuries. 

PMID- 23884076
TI  - Review of Experience of a Statewide Poison Control Center With Pediatric
      Exposures to Oral Antineoplastic Drugs in the Nonmedical Setting.
AB  - The use of oral antineoplastic agents in nonmedical settings continues to
      increase. There are limited data available on pediatric exposures to these
      agents. We sought to identify characteristics of such exposures. We performed a
      retrospective review of database of a statewide poison system from 2000 to 2009
      for all cases of pediatric exposures to oral antineoplastic agents, which took
      place in a nonmedical setting. Data collected include gender, age, agent of
      exposure, dose, drug concentration, reason for exposure, symptoms, outcomes,
      interventions, and length of hospital stay. There were a total of 328 patients.
      The mean average age was 4.1 years. Eighty-nine percentage (n = 293) was
      unintentional. Exposures to 21 different antineoplastic agents were identified.
      Methotrexate (n = 91) and 6-mercaptopurine (n = 47) were the most common agents
      encountered. Two hundred ninety-nine (91%) cases had no symptoms reported. When
      reported, gastrointestinal symptoms (n = 17) and central nervous system sedation
      (n = 6) were most common. One case of pancytopenia was reported. No deaths were
      reported in this series. Sixty-seven percent (n = 220) were managed at home,
      whereas 19 (6%) were admitted to a health care facility. Cases were followed by
      the poison control center for 0.34 days (SD = 1.40). In this study, exposures to
      oral antineoplastics were primarily unintentional, asymptomatic, and managed at
      home. Study limitations include possible reporting bias, inability to objectively
      confirm exposures, and limited duration of monitoring by the poison control
      center. In this retrospective review, no significant morbidity or mortality was
      reported from pediatric exposures to oral antineoplastic drugs in the nonmedical
      setting. 

PMID- 23884077
TI  - Mast Cell Stabilizer Ketotifen Inhibits Gouty Inflammation in Rats.
AB  - Gout, an extremely painful arthritis with relapsing inflammatory attacks, is a
      common inflammatory joint disease in adults. We examined the therapeutic effect
      of ketotifen, a mast cell stabilizer, on monosodium urate (MSU) crystal-induced
      acute inflammation. Eight-week-old male Wistar rats were injected with MSU
      crystals (5 mg per rat) into air pouch. Ketotifen (0, 0.1, 03, and 1 mg/kg) was
      given 1 hour before MSU crystal injection. Lavage histamine, leukocyte counts,
      mast cell counts, nitric oxide, and proinflammatory mediator levels were assessed
      12 hours after MSU injection. Ketotifen significantly inhibited MSU-induced mast
      cell activation and histamine concentration in air pouch lavage. Ketotifen dose
      dependently inhibited MSU-initiated leukocyte infiltration into the air pouch.
      Furthermore, ketotifen significantly decreased proinflammatory mediators,
      including nitric oxide, interleukin-1beta, and interleukin-6, production in MSU
      treated rats. Ketotifen may attenuate MSU-induced acute inflammation by
      inhibiting mast cell activation and leukocyte infiltration in rats. Furthermore,
      ketotifen has the potential to be a new approach in managing patients with gouty
      inflammation in the future. 

PMID- 23884078
TI  - Dynamics of a vertical cavity quantum cascade phonon laser structure.
AB  - Driven primarily by scientific curiosity, but also by the potential applications
      of intense sources of coherent sound, researchers have targeted the phonon laser
      (saser) since the invention of the optical laser over 50 years ago. Here we
      fabricate a vertical cavity structure designed to operate as a saser oscillator
      device at a frequency of 325 GHz. It is based on a semiconductor superlattice
      gain medium, inside a multimode cavity between two acoustic Bragg reflectors. We
      measure the acoustic output of the device as a function of time after applying
      electrical pumping. The emission builds in intensity reaching a steady state on a
      timescale of order 0.1 MUs. We show that the results are consistent with a model
      of the dynamics of a saser cavity exactly analogous to the models used for
      describing laser dynamics. We also obtain estimates for the gain coefficient,
      steady-state acoustic power output and efficiency of the device.

PMID- 23884079
TI  - Antiferromagnetic-like coupling in the cationic iron cluster of thirteen atoms.
AB  - We explore, within the density functional theory in the generalized gradient
      approximation to exchange and correlation, the map of spin isomers of the
      cationic Fe13(+) cluster in connection with recent X-ray magnetic circular
      dichroism spectroscopy experiments [M. Niemeyer et al., Phys. Rev. Lett. 2012,
      108, 057201] which showed an anomalous low magnetic moment per number of 3d holes
      in this cluster. We systematically explore the low-lying magnetic excitations and
      correlate them with structural rearrangements and stability indicators. We obtain
      the observed low magnetic moment per 3d hole as the ground state of Fe13(+) and
      we demonstrate that, as supposed by the experimentalists, the cluster undergoes a
      magnetic transition from a ferromagnetic-like configuration to an
      antiferromagnetic-like one upon ionization. We unravel this unexpected magnetic
      behavior showing that it is concomitant with a Th-deformation of the icosahedral
      structure together with the electronic filling of this particular iron cluster.
      The spin-orbit interaction preserves this magnetic configuration which is
      essentially due to the spin. Our computed magnetic anisotropy energy supports the
      experimental interpretation of the cluster as fluxional due to the very weak
      coupling of the magnetic moment to an easy axis. 

PMID- 23884080
TI  - Synthesis and study of olefin metathesis catalysts supported by redox-switchable
      diaminocarbene[3]ferrocenophanes.
AB  - A redox-switchable ligand, N,N'-dimethyldiaminocarbene[3]ferrocenophane (5), was
      synthesized and incorporated into a series of Ir- and Ru-based complexes.
      Electrochemical and spectroscopic analyses of (5)Ir(CO)2Cl (15) revealed that 5
      displayed a Tolman electronic parameter value of 2050 cm(-1) in the neutral state
      and 2061 cm(-1) upon oxidation. Moreover, inspection of X-ray crystallography
      data recorded for (5)Ir(cis,cis-1,5-cyclooctadiene)Cl (13) revealed that 5 was
      sterically less bulky (%V(Bur) = 28.4) than other known
      diaminocarbene[3]ferrocenophanes, which facilitated the synthesis of
      (5)(PPh3)Cl2Ru(3-phenylindenylid-1-ene) (18). Complex 18 exhibited quasi
      reversible electrochemical processes at 0.79 and 0.98 V relative to SCE, which
      were assigned to the Fe and Ru centers in the complex, respectively, based on UV
      vis and electron pair resonance spectroscopic measurements. Adding 2,3-dichloro
      5,6-dicyanoquinone over the course of a ring-opening metathesis polymerization of
      cis,cis-1,5-cyclooctadiene catalyzed by 18 ([monomer]0/[18]0 = 2500) reduced the
      corresponding rate constant of the reaction by over an order of magnitude (pre
      oxidation: k(obs) = 0.045 s(-1); post-oxidation: k(obs) = 0.0012 s(-1)).
      Subsequent reduction of the oxidized species using decamethylferrocene restored
      catalytic activity (post-reduction: k(obs) = up to 0.016 s(-1), depending on when
      the reductant was added). The difference in the polymerization rates was
      attributed to the relative donating ability of the redox-active ligand (i.e.,
      strongly donating 5 versus weakly donating 5(+)) which ultimately governed the
      activity displayed by the corresponding catalyst.

PMID- 23884081
TI  - Botulinum toxin complex increases paracellular permeability in intestinal
      epithelial cells via activation of p38 mitogen-activated protein kinase.
AB  - Clostridium botulinum produces a large toxin complex (L-TC) that increases
      paracellular permeability in intestinal epithelial cells by a mechanism that
      remains unclear. Here, we show that mitogen-activated protein kinases (MAPKs) are
      involved in this permeability increase. Paracellular permeability was measured by
      FITC-dextran flux through a monolayer of rat intestinal epithelial IEC-6 cells,
      and MAPK activation was estimated from western blots. L-TC of C. botulinum
      serotype D strain 4947 increased paracellular dextran flux and activated
      extracellular signal-regulated kinase (ERK), p38, but not c-Jun N-terminal kinase
      (JNK) in IEC-6 cells. The permeability increase induced by L-TC was abrogated by
      the p38 inhibitor SB203580. These results indicate that L-TC increases
      paracellular permeability by activating p38, but not JNK and ERK. 

PMID- 23884082
TI  - Coenurus cerebralis cysts in the left lateral cerebral ventricle of a ewe.
AB  - A three-and-a-half year-old female Rahmani ewe was presented suffering from
      nervous symptoms. Grossly, a large cyst measuring 7 * 4 cm and weighing 145 g
      occupied the dilated left lateral ventricle. The overlying cerebral tissue was
      thin, atrophied and congested. It tore easily, and the cyst was evacuated
      spontaneously. Microscopically, liquefactive necrosis surrounded by aggregations
      of macrophages, eosinophils, lymphocytes, fibroblasts and giant cells was
      predominantly observed. Hyperplasia and severe necrosis of the ependymal cell
      lining of the lateral ventricle were observed. Extensive subependymal
      inflammatory cell infiltrations, accompanied by neovascularization and
      fibroblastic proliferation, were seen. Based on the gross and histopathological
      lesions and cyst morphology and location, the cyst was diagnosed as Coenurus
      cerebralis. This report describes a rare case of coenurus cyst in the left
      lateral cerebral ventricle of a ewe and the associated lesion. 

PMID- 23884083
TI  - LC-MS characterization and purity assessment of a prototype bispecific antibody.
AB  - Bispecific IgG asymmetric (heterodimeric) antibodies offer enhanced therapeutic
      efficacy, but present unique challenges for drug development. These challenges
      are related to the proper assembly of heavy and light chains. Impurities such as
      symmetric (homodimeric) antibodies can arise with improper assembly. A new method
      to assess heterodimer purity of such bispecific antibody products is needed
      because traditional separation-based purity assays are unable to separate or
      quantify homodimer impurities. This paper presents a liquid chromatography-mass
      spectrometry (LC-MS)-based method for evaluating heterodimeric purity of a
      prototype asymmetric antibody containing two different heavy chains and two
      identical light chains. The heterodimer and independently expressed homodimeric
      standards were characterized by two complementary LC-MS techniques: Intact
      protein mass measurement of deglycosylated antibody and peptide map analyses.
      Intact protein mass analysis was used to check molecular integrity and
      composition. LC-MS(E) peptide mapping of Lys-C digests was used to verify protein
      sequences and characterize post-translational modifications, including C-terminal
      truncation species. Guided by the characterization results, a heterodimer purity
      assay was demonstrated by intact protein mass analysis of pure deglycosylated
      heterodimer spiked with each deglycosylated homodimeric standard. The assay was
      capable of detecting low levels (2%) of spiked homodimers in conjunction with co
      eluting half antibodies and multiple mass species present in the homodimer
      standards and providing relative purity differences between samples. Detection of
      minor homodimer and half-antibody C-terminal truncation species at levels as low
      as 0.6% demonstrates the sensitivity of the method. This method is suitable for
      purity assessment of heterodimer samples during process and purification
      development of bispecific antibodies, e.g., clone selection. 

PMID- 23884085
TI  - Transcriptional suppression of CYP2A13 expression by lipopolysaccharide in
      cultured human lung cells and the lungs of a CYP2A13-humanized mouse model.
AB  - CYP2A13, a human P450 enzyme preferentially expressed in the respiratory tract,
      is highly efficient in the metabolic activation of tobacco-specific nitrosamines.
      The aim of this study was to test the hypothesis that inflammation suppresses
      CYP2A13 expression in the lung, thus explaining the large interindividual
      differences in CYP2A13 levels previously found in human lung biopsy samples. We
      first demonstrated that the bacterial endotoxin lipopolysaccharide (LPS) and the
      proinflammatory cytokine IL-6 can suppress CYP2A13 messenger RNA (mRNA)
      expression in the NCI-H441 human lung cell line. We then report that an ip
      injection of LPS (1mg/kg), which induces systemic and lung inflammation, caused
      substantial reductions in CYP2A13 mRNA (~50%) and protein levels (~80%) in the
      lungs of a newly generated CYP2A13-humanized mouse model. We further identified
      two critical CYP2A13 promoter regions, one (major) between -484 and -1008bp and
      the other (minor) between -134 and -216bp, for the response to LPS, through
      reporter gene assays in H441 cells. The potential involvement of the nuclear
      factor NF-kappaB in LPS-induced CYP2A13 downregulation was suggested by
      identification of putative NF-kappaB binding sites within the LPS response
      regions and effects of an NF-kappaB inhibitor (pyrrolidine dithiocarbamate) on
      CYP2A13 expression in H441 cells. Results from gel shift assays further confirmed
      binding of NF-kappaB-like nuclear proteins of H441 cells to the major LPS
      response region of the CYP2A13 promoter. Thus, our findings strongly support the
      hypothesis that CYP2A13 levels in human lung can be suppressed by inflammation
      associated with disease status in tissue donors, causing underestimation of
      CYP2A13 levels in healthy lung. 

PMID- 23884084
TI  - GHS-R1a signaling in the DMH and VMH contributes to food anticipatory activity.
AB  - BACKGROUND: Rats that have restricted access to food at a fixed time point of the
      circadian phase display high levels of food anticipatory activity (FAA). The
      orexigenic hormone ghrelin has been implicated in the regulation of FAA. However,
      it is not known via which brain area ghrelin exerts this effect. Growth hormone
      secretagogue receptor 1a (GHS-R1a) is highly expressed in the hypothalamus,
      including the dorsomedial hypothalamus (DMH) and the ventromedial hypothalamus
      (VMH). These two hypothalamic areas have been reported to play a role in FAA. AIM
      OF THE STUDY: To examine the role of GHS-R1a signaling in the DMH and VMH in FAA.
      DESIGN: Adeno-associated virus expressing a shRNA directed against GHS-R1a was
      used to establish local knockdown of GHS-R1a in the DMH and VMH in rats. Rats
      were subsequently subjected to a restricted feeding schedule (RFS). RESULTS:
      Under ad libitum conditions, knockdown of GHS-R1a in the VMH increased food
      intake and body weight gain. In addition, GHS-R1a knockdown in VMH and DMH
      reduced body temperature and running wheel activity (RWA). When rats were
      subjected to a RFS, the main effect of GHS-R1a knockdown in both DMH and VMH was
      a decrease in RWA and an attenuation of body weight loss. Rats with knockdown of
      GHS-R1a in DMH and VMH showed a delay in onset of FAA. In addition, GHS-R1a
      knockdown in DMH resulted in a reduction of FAA amplitude. CONCLUSION: This is
      the first study to investigate the effect of local hypothalamic knockdown of GHS
      R1a on FAA. Our results implicate hypothalamic GHS-R1a signaling in the
      regulation of FAA. Nevertheless, some FAA remained, suggesting that a distributed
      network of brain areas and signaling pathways is involved in the development of
      FAA.

PMID- 23884086
TI  - Selective inhibition of the unfolded protein response: targeting catalytic sites
      for Schiff base modification.
AB  - Constitutive protein misfolding in the endoplasmic reticulum (ER) can lead to
      cellular toxicity and disease. Consequently, the protein folding environment
      within the ER is highly optimised and tightly regulated by the unfolded protein
      response (UPR). The apparent convergence of myriad diseases upon proteostasis in
      the ER has triggered a broad effort to identify selective inhibitors of the UPR.
      In particular, the most ancient component of this cellular stress pathway, the
      transmembrane protein IRE1, represents an appealing target for pharmacological
      intervention. Several inhibitors of IRE1 have recently been reported, each
      containing an aldehyde moiety that forms an unusual, highly selective Schiff base
      with a single key lysine (K907) within the RNase domain. Here we review the
      progress made in chemical genetic manipulation of IRE1 and the unfolded protein
      response and discuss computational strategies to rationalise the selectivity of
      covalently active small molecules for their targets. As an exemplar, we provide
      additional evidence that K907 of IRE1 is buried within a particularly unusual
      environment that facilitates Schiff base formation. New free-energy calculations
      within a molecular dynamics (MD) simulation framework show that the pKa of K907
      is reduced by ~3.6 pKa units, relative to the model pKa of lysine in water. This
      significant pKa perturbation provides additional insights into the precise
      requirements for inhibition and for RNase catalysis by IRE1. Our computational
      method may represent a general approach for identifying potential covalent
      inhibitory lysine sites within buried protein cavities.

PMID- 23884087
TI  - Potential for the international spread of middle East respiratory syndrome in
      association with mass gatherings in saudi arabia.
AB  - BACKGROUND: A novel coronavirus (MERS-CoV) causing severe, life-threatening
      respiratory disease has emerged in the Middle East at a time when two
      international mass gatherings in Saudi Arabia are imminent. While MERS-CoV has
      already spread to and within other countries, these mass gatherings could further
      amplify and/or accelerate its international dissemination, especially since the
      origins and geographic source of the virus remain poorly understood. METHODS: We
      analyzed 2012 worldwide flight itinerary data and historic Hajj pilgrim data to
      predict population movements out of Saudi Arabia and the broader Middle East to
      help cities and countries assess their potential for MERS-CoV importation. We
      compared the magnitude of travel to countries with their World Bank economic
      status and per capita healthcare expenditures as surrogate markers of their
      capacity for timely detection of imported MERS-CoV and their ability to mount an
      effective public health response. RESULTS: 16.8 million travelers flew on
      commercial flights out of Saudi Arabia, Jordan, Qatar, and the United Arab
      Emirates between June and November 2012, of which 51.6% were destined for India
      (16.3%), Egypt (10.4%), Pakistan (7.8%), the United Kingdom (4.3%), Kuwait
      (3.6%), Bangladesh (3.1%), Iran (3.1%) and Bahrain (2.9%). Among the 1.74 million
      foreign pilgrims who performed the Hajj last year, an estimated 65.1% originated
      from low and lower-middle income countries. CONCLUSION: MERS-CoV is an emerging
      pathogen with pandemic potential with its apparent epicenter in Saudi Arabia,
      where millions of pilgrims will imminently congregate for two international mass
      gatherings. Understanding global population movements out of the Middle East
      through the end of this year's Hajj could help direct anticipatory MERS-CoV
      surveillance and public health preparedness to mitigate its potential global
      health and economic impacts.

PMID- 23884088
TI  - Catalytic asymmetric exo-selective [6+3] cycloaddition of iminoesters with
      fulvenes.
AB  - A novel exo-selective [6+3] cycloaddition approach for the highly
      enantioselective synthesis of polysubstituted piperidines was developed. The
      developed methodology was applied in a one-pot [6+3]-[4+2] dicycloaddition,
      allowing the construction of structurally and stereochemically rich polycyclic
      compounds from simple building blocks. 

PMID- 23884089
TI  - Preoperative left ventricular function in degenerative mitral valve disease.
AB  - AIM: The aim of the study is to determine the impact of the underlying etiology
      (Barlow's disease or fibroelastic deficiency) on left ventricular function in
      patients with degenerative mitral valve disease and severe mitral regurgitation.
      METHODS: We studied 233 patients (mean age: 53.8 +/- 12.9) undergoing surgery for
      severe mitral regurgitation due to degenerative mitral valve disease at Almazov
      Federal Heart Centre between 2009 and 2011. Pathologic diagnoses for valvular
      tissue specimens were provided by an experienced pathologist. Preoperative strain
      and strain rate were determined using speckle tracking (Vivid 7 Dimension,
      EchoPAC'08). RESULTS: Barlow's disease was identified by the pathologist in 60
      patients (25.8%), and fibroelastic deficiency in 173 patients (74.2%). There were
      no significant differences between groups in preoperative mitral regurgitation
      volume (70.5 +/- 9.6 vs. 71.6 +/- 8.5 ml, P = 0.40), and in global systolic
      (ejection fraction: 52.7 +/- 6.6 vs. 52.0 +/- 7.4%, P = 0.53) and diastolic
      (E/e': 12.2 +/- 3.9 vs. 12.8 +/- 4.2, P = 0.35) left ventricular function.
      Despite the lack of difference in ejection fraction and diastolic tissue Doppler
      parameters, in patients with Barlow's disease in comparison with fibroelastic
      deficiency a significant decrease of the left ventricular longitudinal systolic
      strain (-13.5 +/- 2.2 vs. -15.6 +/- 2.3%, P = 0.00001) and early diastolic strain
      rate (1.04 +/- 0.20 vs. 1.14 +/- 0.18 s, P = 0.0004) were detected. CONCLUSION:
      Patients with severe mitral regurgitation due to Barlow's disease have a lower
      preoperative left ventricular systolic function than those with fibroelastic
      deficiency, which may affect their postoperative prognosis.

PMID- 23884090
TI  - Flight loss linked to faster molecular evolution in insects.
AB  - The loss of flight ability has occurred thousands of times independently during
      insect evolution. Flight loss may be linked to higher molecular evolutionary
      rates because of reductions in effective population sizes (Ne) and relaxed
      selective constraints. Reduced dispersal ability increases population
      subdivision, may decrease geographical range size and increases (sub)population
      extinction risk, thus leading to an expected reduction in Ne. Additionally,
      flight loss in birds has been linked to higher molecular rates of energy-related
      genes, probably owing to relaxed selective constraints on energy metabolism. We
      tested for an association between insect flight loss and molecular rates through
      comparative analysis in 49 phylogenetically independent transitions spanning
      multiple taxa, including moths, flies, beetles, mayflies, stick insects,
      stoneflies, scorpionflies and caddisflies, using available nuclear and
      mitochondrial protein-coding DNA sequences. We estimated the rate of molecular
      evolution of flightless (FL) and related flight-capable lineages by ratios of non
      synonymous-to-synonymous substitutions (dN/dS) and overall substitution rates
      (OSRs). Across multiple instances of flight loss, we show a significant pattern
      of higher dN/dS ratios and OSRs in FL lineages in mitochondrial but not nuclear
      genes. These patterns may be explained by relaxed selective constraints in FL
      ectotherms relating to energy metabolism, possibly in combination with reduced
      Ne. 

PMID- 23884091
TI  - To kill a kangaroo: understanding the decision to pursue high-risk/high-gain
      resources.
AB  - In this paper, we attempt to understand hunter-gatherer foraging decisions about
      prey that vary in both the mean and variance of energy return using an expected
      utility framework. We show that for skewed distributions of energetic returns,
      the standard linear variance discounting (LVD) model for risk-sensitive foraging
      can produce quite misleading results. In addition to creating difficulties for
      the LVD model, the skewed distributions characteristic of hunting returns create
      challenges for estimating probability distribution functions required for
      expected utility. We present a solution using a two-component finite mixture
      model for foraging returns. We then use detailed foraging returns data based on
      focal follows of individual hunters in Western Australia hunting for high
      risk/high-gain (hill kangaroo) and relatively low-risk/low-gain (sand monitor)
      prey. Using probability densities for the two resources estimated from the
      mixture models, combined with theoretically sensible utility curves characterized
      by diminishing marginal utility for the highest returns, we find that the
      expected utility of the sand monitors greatly exceeds that of kangaroos despite
      the fact that the mean energy return for kangaroos is nearly twice as large as
      that for sand monitors. We conclude that the decision to hunt hill kangaroos does
      not arise simply as part of an energetic utility-maximization strategy and that
      additional social, political or symbolic benefits must accrue to hunters of this
      highly variable prey. 

PMID- 23884092
TI  - Are there species smaller than 1 mm?
AB  - The rapid advance in genetic sequencing technologies has provided an
      unprecedented amount of data on the biodiversity of meiofauna. It was hoped that
      these data would allow the identification and counting of species, distinguished
      as tight clusters of similar genomes. Surprisingly, this appears not to be the
      case. Here, we begin a theoretical discussion of this phenomenon, drawing on an
      individual-based ecological model to inform our arguments. The determining factor
      in the emergence (or not) of distinguishable genetic clusters in the model is the
      product of population size with mutation rate-a measure of the adaptability of
      the population as a whole. This result suggests that indeed one should not expect
      to observe clearly distinguishable species groupings in data gathered from
      ultrasequencing of meiofauna. 

PMID- 23884093
TI  - Post-hatch heat warms adult beaks: irreversible physiological plasticity in
      Japanese quail.
AB  - Across taxa, the early rearing environment contributes to adult morphological and
      physiological variation. For example, in birds, environmental temperature plays a
      key role in shaping bill size and clinal trends across latitudinal/thermal
      gradients. Such patterns support the role of the bill as a thermal window and in
      thermal balance. It remains unknown whether bill size and thermal function are
      reversibly plastic. We raised Japanese quail in warm (30 degrees C) or cold (15
      degrees C) environments and then at a common intermediate temperature. We
      predicted that birds raised in cold temperatures would develop smaller bills than
      warm-reared individuals, and that regulation of blood flow to the bill in
      response to changing temperatures would parallel the bill's role in thermal
      balance. Cold-reared birds developed shorter bills, although bill size exhibited
      'catch-up' growth once adults were placed at a common temperature. Despite having
      lived in a common thermal environment as adults, individuals that were initially
      reared in the warmth had higher bill surface temperatures than cold-reared
      individuals, particularly under cold conditions. This suggests that blood vessel
      density and/or the control over blood flow in the bill retained a memory of early
      thermal ontogeny. We conclude that post-hatch temperature reversibly affects
      adult bill morphology but irreversibly influences the thermal physiological role
      of bills and may play an underappreciated role in avian energetics. 

PMID- 23884095
TI  - Boosting innate immunity: development and validation of a cell-based screening
      assay to identify LL-37 inducers.
AB  - Innate immunity, the front line of our defence against pathogens, relies, to a
      great extent, on the production of antimicrobial peptides (AMPs). These peptides
      exhibit antimicrobial activity and immunomodulatory properties. In humans, AMPs
      include the defensins (alpha- and beta-families) and the cathelicidin, LL-37.
      Bacterial resistance against antibiotics is a growing concern, and novel
      antimicrobial strategies are needed urgently. Hence, the concept of strengthening
      immune defences against infectious microbes by inducing AMP expression may
      represent novel or complementary pharmaceutical interventions in the treatment or
      prevention of infections. We have developed and validated a robust cell-based
      reporter assay for LL-37 expression, which serves as a marker for a healthy
      epithelial barrier. This reporter assay can be a powerful tool for high
      throughput screenings. We first employed our assay to screen a panel of histone
      deacetylase inhibitors and derivatives, and then the Prestwick Chemical Library
      of Food and Drug Administration-approved compounds. After hit confirmation and
      independent validation in the parental cell line we identified five novel
      inducers of LL-37. This reporter assay will help to identify novel drug
      candidates for the treatment and prevention of infections. Importantly, the
      pattern of hits obtained may suggest cellular pathways and key mediators involved
      in the regulation of AMP expression. 

PMID- 23884096
TI  - Interference of silica nanoparticles with the traditional Limulus amebocyte
      lysate gel clot assay.
AB  - Endotoxin contaminations of engineered nanomaterials can be responsible for
      observed biological responses, especially for misleading results in in vitro test
      systems, as well as in vivo studies. Therefore, endotoxin testing of
      nanomaterials is necessary to benchmark their influence on cells. Here, we tested
      the traditional Limulus amebocyte lysate gel clot assay for the detection of
      endotoxins in nanoparticle suspensions with a focus on possible interference of
      the particles with the test system. We systematically investigated the effects of
      nanomaterials made of, or covered by, the same material. Different types of bare
      or PEGylated silica nanoparticles, as well as iron oxide-silica core shell
      nanoparticles, were tested. Detailed inhibition/enhancement controls revealed
      enhanced activity in the Limulus coagulation cascade for all particles with bare
      silica surface. In comparison, PEGylation led to a lower degree of enhancement.
      These results indicate that the protein-particle interactions are the basis for
      the observed inhibition and enhancement effects. The enhancement activity of a
      particle type was positively related to the calculated particle surface area. For
      most silica particles tested, a dilution of the sample within the maximum valid
      dilution was sufficient to overcome non-valid enhancement, enabling semi
      quantification of the endotoxin contamination.

PMID- 23884094
TI  - Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune
      response.
AB  - NOD1 and NOD2 are members of the NOD-like receptor family of cytosolic pattern
      recognition receptors that recognize specific fragments of the bacterial cell
      wall component peptidoglycan. Neisseria species are unique amongst Gram-negative
      bacteria in that they turn over large amounts of peptidoglycan during growth. We
      examined the ability of NOD1 and NOD2 to recognize Neisseria gonorrhoeae, and
      determined the role of NOD-dependent signaling in regulating the immune response
      to gonococcal infection. Gonococci, as well as conditioned medium from mid
      logarithmic phase grown bacteria, were capable of activating both human NOD1 and
      NOD2, as well as mouse NOD2, leading to the activation of the transcription
      factor NF-kappaB and polyubiquitination of the adaptor receptor-interacting
      serine-threonine kinase 2. We identified a number of cytokines and chemokines
      that were differentially expressed in wild type versus NOD2-deficient macrophages
      in response to gonococcal infection. Moreover, NOD2 signaling up-regulated
      complement pathway components and cytosolic nucleic acid sensors, suggesting a
      broad impact of NOD activation on innate immunity. Thus, NOD1 and NOD2 are
      important intracellular regulators of the immune response to infection with N.
      gonorrhoeae. Given the intracellular lifestyle of this pathogen, we believe these
      cytosolic receptors may provide a key innate immune defense mechanism for the
      host during gonococcal infection. 

PMID- 23884097
TI  - A novel thermally stable hydroperoxo-copper(II) complex in a Cu(N2O2) chromophore
      of a potential N4O2 donor Schiff base ligand: synthesis, structure and catalytic
      studies.
AB  - The generation and study of metal-hydroperoxo/metal-peroxo (LCu(II)-OOH or
      LCu(II)-OO) complexes is a fascinating area of research of many chemical and
      biochemical researchers, because of their involvement as active intermediates in
      many biological and industrial catalytic oxidation processes. For this purpose we
      have designed a bulky hexa-coordinating ligand with potential N4O2 donor atoms
      which could provide an opportunity to synthesize a mononuclear Cu(II) complex
      with an aim to utilize it in the catalytic oxidation of aromatic hydrocarbons by
      an environmentally benign oxidant, H2O2. The Cu(II) complex (1) was structurally
      characterized and found to have square-planar geometry with the two pyrazolyl
      groups remaining in dangling mode. A novel mononuclear complex [Et3NH][LCu(II)
      OOH] (2) was found to form in the reaction between 1 and H2O2 in the presence of
      Et3N. The presence of this dangling groups favours the stability of hydroperoxo
      species, [LCu-OOH](-) (2) through H-bonding with the coordinated phenoxo oxygen
      atom, which was confirmed by ESI-MS(+) and MS(-) (m/z) mass analysis and DFT
      calculations. This complex was found to be thermally stable at room temperature
      [k(d) = (5.67 +/- 0.03) * 10(-5) s(-1) at 25  degrees C] and may be due to the
      formation of O-O-H...O(phenoxo) H-bonding as delineated by the DFT calculations.
      Complex 1 was found to be an efficient catalyst for the oxidation of aromatic
      hydrocarbons to the corresponding aldehyde and alcohol in 2:1 mole ratio with TON
      ~300.

PMID- 23884098
TI  - Searching and review on the Three Rs information in Korea: time for quality
      assessment and continued education.
AB  - Scientists planning research that involves the use of animals are required by
      international and/or national law to examine the possibilities for the
      implementation of Replacement, Reduction and/or Refinement (the Three Rs
      principles of Russell and Burch) in experiments for research, testing, and
      education. There are two Korean laws legislating humane use of animals and
      ethical review prior to animal experiments. This report reviews current practice
      of the literature search by the researchers and protocol review by the
      Institutional Animal Care and Use Committees on the Replacement, Reduction and
      Refinement alternatives in Korea. The promotion and protection of the laboratory
      animals are one of the core competencies of investigators exploring the ethical
      conduct of research and good science.

PMID- 23884100
TI  - Genetic variants and signatures of selective sweep of Hanwoo population (Korean
      native cattle).
AB  - Although there have been many studies of native Korean cattle, Hanwoo, there have
      been no selective sweep studies in these animals. This study was performed to
      characterize genetic variation and identify selective signatures. We sequenced
      the genomes of 12 cattle, and identified 15125420 SNPs, 1768114 INDELs, and 3445
      CNVs. The SNPs, INDELs, and CNVs were similarly distributed throughout the
      genome, and highly variable regions were shown to contain the BoLA family and
      GPR180, which are related to adaptive immunity. We also identified the
      domestication footprints of the Hanwoo population by searching for selective
      sweep signatures, which revealed the RCN2 gene related to BPV resistance. The
      results of this study may contribute to genetic improvement of the Hanwoo
      population in Korea.

PMID- 23884099
TI  - microRNA biomarkers in cystic diseases.
AB  - microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by
      targeting the 3'-untranslated region of multiple target genes. Pathogenesis
      results from defects in several gene sets; therefore, disease progression could
      be prevented using miRNAs targeting multiple genes. Moreover, recent studies
      suggest that miRNAs reflect the stage of the specific disease, such as
      carcinogenesis. Cystic diseases, including polycystic kidney disease, polycystic
      liver disease, pancreatic cystic disease, and ovarian cystic disease, have common
      processes of cyst formation in the specific organ. Specifically, epithelial cells
      initiate abnormal cell proliferation and apoptosis as a result of alterations to
      key genes. Cysts are caused by fluid accumulation in the lumen. However, the
      molecular mechanisms underlying cyst formation and progression remain unclear.
      This review aims to introduce the key miRNAs related to cyst formation, and we
      suggest that miRNAs could be useful biomarkers and potential therapeutic targets
      in several cystic diseases.

PMID- 23884101
TI  - The protective effect of Prunella vulgaris ethanol extract against vascular
      inflammation in TNF-alpha-stimulated human aortic smooth muscle cells.
AB  - Atherosclerosis, which manifests as acute coronary syndrome, stroke, and
      peripheral arterial diseases, is a chronic inflammatory disease of the arterial
      wall. Prunella vulgaris, a perennial herb with a worldwide distribution, has been
      used as a traditional medicine in inflammatory disease. Here, we investigated the
      effects of P. vulgaris ethanol extract on TNF-alpha-induced inflammatory
      responses in human aortic smooth muscle cells (HASMCs). We found that P. vulgaris
      ethanol extract inhibited adhesion of monocyte/macrophage-like THP-1 cells to
      activated HASMCs. It also decreased expression of intercellular adhesion molecule
      1, vascular cell adhesion molecule-1, E-selectin and ROS, No production in TNF
      alpha-induced HASMCs and reduced NF-kB activation. Furthermore, P. vulgaris
      extract suppressed TNF-alpha-induced phosphorylation of p38 mitogen-activated
      protein kinase (MAPK) and extracellular signal-regulated kinase (ERK). These
      results demonstrate that P. vulgaris possesses antiinflammatory properties and
      can regulate TNF-alpha-induced expression of adhesion molecules by inhibiting the
      p38 MAPK/ERK signaling pathway.

PMID- 23884102
TI  - A novel pattern recognition protein of the Chinese oak silkmoth, Antheraea
      pernyi, is involved in the pro-PO activating system.
AB  - In this paper, we firstly reported a C-type lectin cDNA clone of 1029 bps from
      the larvae of A. Pernyi (Ap-CTL) using PCR and RACE techniques. The full-length
      cDNA contains an open reading frame encoding 308 amino acid residues which has
      two different carbohydrate-recognition domains (CRDs) arranged in tandem. To
      investigate the biological activities in the innate immunity, recombinant Ap-CTL
      was expressed in E. coli with a 6-histidine at the amino-terminus (Ap-rCTL).
      Besides acted as a broad-spectrum recognition protein binding to a wide range of
      PAMPs and microorganisms, Ap-rCTL also had the ability to recognize and trigger
      the agglutination of bacteria and fungi. In the proPO activation assay, Ap-rCTL
      specifically restored the PO activity of hemolymph blocked by anti- Ap-rCTL
      antibody in the presence of different PAMPs or microorganisms. In summary, Ap
      rCTL plays an important role in insect innate immunity as an pattern recognition
      protein.

PMID- 23884103
TI  - Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway.
AB  - Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in
      hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless,
      precise mechanism involved in ET-1-induced hyperpigmentation is still undefined.
      Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key
      element in melanosome formation. Therefore, we speculated that GPNMB was
      correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin
      synthesis was significantly up-regulated, accompanying with increased expression
      of GPNMB and microphthalmia- associated transcription factor (MITF). Total number
      of melanosomes and melanin synthesis were sharply reduced via GPNMB-siRNA
      transfection, indicating ET-1-induced pigmentation by GPNMB-dependent manner.
      Furthermore, MITFsiRNA transfection strikingly inhibited GPNMB expression and the
      melanogenesis, and this suppression failed to be alleviated by ET-1 stimulation.
      All of these results demonstrated that ET-1 can trigger melanogenesis via the
      MITF-regulated GPNMB pathway. Taken together, these findings will provide a new
      explanation of how ET-1 induces hyperpigmentation, and possibly supply a new
      strategy for cosmetic studies.

PMID- 23884104
TI  - Neuroprotective effects of the antioxidant action of 2-cyclopropylimino-3-methyl
      1,3-thiazoline hydrochloride against ischemic neuronal damage in the brain.
AB  - Ischemia is characterized by oxidative stress and changes in the antioxidant
      defense system. Our recent in vitro study showed that 2-cyclopropylimino-3-methyl
      1,3-thiazoline hydrochloride protects cortical astrocytes against oxidative
      stress. In the current study, we examined the effects of 2-cyclopropylimino-3
      methyl- 1,3-thiazoline hydrochloride on ischemia-induced neuronal damage in a
      gerbil ischemia/reperfusion models. Extensive neuronal death in the hippocampal
      CA1 area was observed 4 days after ischemia/reperfusion. Intraperitoneal
      injection of 2-cyclopropylimino- 3-methyl-1,3-thiazoline hydrochloride (0.3 mg/kg
      body weight) significantly prevented neuronal death in the CA1 region of the
      hippocampus in response to transient forebrain ischemia. 2-Cyclopropylimino-3
      methyl-1,3-thiazoline hydrochloride administration reduced ischemia-induced
      increases in reactive oxygen species levels and malondialdehyde content. It also
      attenuated the associated reductions in glutathione level and superoxide
      dismutase, catalase, and glutathione peroxidase activities. Taken together, our
      results suggest that 2-cyclopropylimino- 3-methyl-1,3-thiazoline hydrochloride
      protects against ischemia-induced neuronal damage by reducing oxidative stress
      through its antioxidant actions.

PMID- 23884105
TI  - Mouse mannose-binding lectin-A and ficolin-A inhibit lipopolysaccharide-mediated
      pro-inflammatory responses on mast cells.
AB  - It is unknown how soluble pattern-recognition receptors in blood, such as mannose
      binding lectin (MBL) and ficolins, modulate mast cell-mediated inflammatory
      responses. We investigate how mouse MBL-A or ficolin-A regulate mouse bone marrow
      derived mast cells (mBMMCs)-derived inflammatory response against bacterial
      lipopolysaccharide (LPS) stimulation. LPS-mediated pro-inflammatory cytokine
      productions on mBMMCs obtained from Toll-like receptor4 (TLR4)-deficient mice,
      TLR2-defficient mice, and their wildtype, were specifically attenuated by the
      addition of either mouse MBL-A or ficolin-A in a dose-dependent manner. However,
      the inhibitory effects by mouse MBL-A or ficolin-A were restored by the addition
      of mannose or N-acetylglucosamine, respectively. These results suggest that mouse
      MBL-A and ficolin-A bind to LPS via its carbohydrate-recognition domain and
      fibrinogen-like domain, respectively, whereby cytokine production by LPS-mediated
      TLR4 in mBMMCs appears to be down-regulated, indicating that mouse MBL and
      ficolin may have an inhibitory function toward mouse TLR4-mediated excessive
      inflammation on the mast cells.

PMID- 23884106
TI  - Antiproliferative effect of benzimidazole anthelmintics albendazole,
      ricobendazole, and flubendazole in intestinal cancer cell lines.
AB  - This study aimed to test the antiproliferative effect of three benzimidazole
      anthelmintics in intestinal cancer cells and to investigate whether these drugs,
      which inhibit tubulin polymerization, can potentiate the efficacy of the
      microtubule-stabilizing drug paclitaxel (PTX). Four intestinal cancer cell lines,
      SW480, SW620, HCT8, and Caco2, with different origins and growth characteristics
      were used. The antiproliferative effect of albendazole (ABZ), ricobendazole
      (RBZ), flubendazole (FLU), and their combinations with PTX was tested using three
      different end-point viability assays, cell cycle distribution analysis, and the x
      CELLigence System for real-time cell analysis. ABZ and FLU inhibited cell
      proliferation significantly in a concentration-dependent and time-dependent
      manner through cell arrest in the G2/M phase. RBZ was not effective at any
      concentration tested. The cell lines differed in sensitivity to FLU and ABZ, with
      HCT8 being the most sensitive, showing IC50 values for ABZ and FLU that reached
      0.3 and 0.9 MUmol/l, respectively. Combinations of PTX+ABZ and PTX+FLU decreased
      cell viability more effectively when compared with treatment with individual
      drugs alone. The anthelmintic benzimidazole drugs ABZ and FLU show a significant
      cytostatic effect and potentiate the efficacy of PTX in intestinal cancer cells.

PMID- 23884107
TI  - Magnesium: are we better off without it?

PMID- 23884108
TI  - Genetic control of inflorescence architecture during rice domestication.
AB  - Inflorescence architecture is a key agronomical factor determining grain yield,
      and thus has been a major target of cereal crop domestication. Transition from a
      spread panicle typical of ancestral wild rice (Oryza rufipogon Griff.) to the
      compact panicle of present cultivars (O. sativa L.) was a crucial event in rice
      domestication. Here we show that the spread panicle architecture of wild rice is
      controlled by a dominant gene, OsLG1, a previously reported SBP-domain
      transcription factor that controls rice ligule development. Association analysis
      indicates that a single-nucleotide polymorphism-6 in the OsLG1 regulatory region
      led to a compact panicle architecture in cultivars during rice domestication. We
      speculate that the cis-regulatory mutation can fine-tune the spatial expression
      of the target gene, and that selection of cis-regulatory mutations might be an
      efficient strategy for crop domestication. 

PMID- 23884109
TI  - Exploring and exploiting the synergy of non-covalent interactions on the surface
      of gold nanoparticles for fluorescent turn-on sensing of bacterial
      lipopolysaccharide.
AB  - The sensing of lipopolysaccharide (LPS) relies on the synergy of multiple
      electrostatic and hydrophobic interactions between LPS and the sensor. However,
      how non-covalent interactions are coordinated to impel the recognition process
      still remains elusive, and the exploration of which would promote the development
      of LPS sensors with higher specificity and sensitivity. In this work, we
      hypothesize that Au NPs would provide a straightforward and flexible platform for
      studying the synergy of non-covalent interactions. The detailed mechanism of
      interactions between the designed fluorescent probes and Au NPs with two distinct
      surface properties was systematically explored. We demonstrated that only when
      the electrostatic attraction and hydrophobic stacking are both present, the
      binding of fluorescent probes onto Au NPs can be not only highly efficient, but
      also positively cooperative. After that, hybrid systems that consist of Au NPs
      and surface-assembled fluorescent probes were exploited for fluorescent turn-on
      sensing of LPS. The results show that the sensitivity and selectivity to LPS
      relies strongly on the binding affinity between fluorescent probes and Au NPs.
      Fluorescent probes assembled Au NPs thus provide an attractive platform for
      further optimization of the sensitivity/selectivity of LPS sensing. 

PMID- 23884110
TI  - Double recognition of dopamine based on a boronic acid functionalized
      poly(aniline-co-anthranilic acid)-molecularly imprinted polymer composite.
AB  - In this work, we report a competitive sensor performing "double recognition" for
      the specific capture of dopamine (DA) with the combination of boronic acid
      functional groups and molecularly imprinted cavities based on poly(aniline-co
      anthranilic acid) (PANANA) as the support material. This novel imprinting
      receptor bearing a covalent ester linkage to DA via boronic acid functional
      groups was prepared and applied as a recognition element in the construction of
      the electrochemical sensor. For the first time, aminophenylboronic acids (APBAs)
      and vinyl groups were both introduced onto the surface of PANANA nanomaterials.
      Then, selective copolymerization of acrylamide and ethylene glycol dimethacrylate
      (EGDMA) in the presence of the template DA was further achieved at the surface of
      APBA and vinyl group functionalized PANANA. The double recognition through the
      functional groups (boronic acids) and the shape of the cavities endowed this
      sensor with a specific affinity for the template DA in the presence of other
      interferents, such as norepinephrine (NE), epinephrine (EP), ascorbic acid (AA)
      and uric acid (UA). Moreover, the results obtained from a series of
      electrochemical experiments proved that this receptor had a good adsorption
      capacity and a fast mass transfer rate for DA. Thus, a novel electrochemical
      sensor with good selectivity and sensitivity was constructed with a linear
      response to the DA concentration in the range from 1.0 * 10(-8) to 1.0 * 10(-5) M
      and a detection limit of 3.33 * 10(-9) M (S/N = 3). Besides, this novel
      electrochemical sensor was successfully applied to the detection of DA in DA
      injected and human plasma samples. 

PMID- 23884111
TI  - Use of clopidogrel and proton pump inhibitors after a serious acute coronary
      event: risk of coronary events and peptic ulcer bleeding.
AB  - Some pharmacokinetic studies have reported that proton pump inhibitors (PPIs)
      reduce the activity of clopidogrel, but the results of studies assessing clinical
      outcomes in patients receiving both drugs are inconsistent. We have therefore
      carried out a population-based cohort study with nested case-control analysis, in
      order to evaluate changes in the risk of cardiovascular and peptic ulcer bleeding
      (PUB) events associated with PPI use in patients receiving clopidogrel. A total
      of 42,542 patients aged 50-84 years in 2000-2007 who survived an acute coronary
      event were identified in two UK-based primary care databases (The Health
      Improvement Network and the General Practice Research Database). Individuals were
      followed up to identify incident cases of non-fatal myocardial
      infarction/coronary death (n = 2,546) and PUB (n = 194). Controls were frequency
      matched to cases by age, sex and calendar year. Compared with PPI non-use,
      current continuous PPI use was not associated with a significant change in risk
      of non-fatal myocardial infarction/coronary death among current continuous users
      of clopidogrel monotherapy (relative risk [RR], 1.06; 95% confidence interval
      [95% CI], 0.47 to 2.36) or dual antiplatelet therapy (DAT; RR, 0.80; 95% CI, 0.47
      to 1.37) who initiated their antiplatelet therapy shortly after their coronary
      event. Among patients prescribed DAT at the start date, the RR of PUB events
      associated with current PPI use initiated at the start date was 0.66 (95% CI,
      0.27 to 1.60). 

PMID- 23884112
TI  - Oligonucleotide tagging for copper-free click conjugation.
AB  - Copper-free click chemistry between cyclooctynes and azide is a mild, fast and
      selective technology for conjugation of oligonucleotides. However, technology for
      site-specific introduction of the requisite probes by automated protocols is
      scarce, while the reported cyclooctynes are large and hydrophobic. In this work,
      it is demonstrated that the introduction of bicyclo[6.1.0]nonyne (BCN) into
      synthetic oligonucleotides is feasible by standard solid-phase phosphoramidite
      chemistry. A range of phosphoramidite building blocks is presented for
      incoporation of BCN or azide, either on-support or in solution. The usefulness of
      the approach is demonstrated by the straightforward and high-yielding conjugation
      of the resulting oligonucleotides, including biotinylation, fluorescent labeling,
      dimerization and attachment to polymer. 

PMID- 23884113
TI  - TDAE strategy for the synthesis of 2,3-diaryl N-tosylaziridines.
AB  - We report herein an original and rapid synthesis of 2,3-diaryl N-tosylaziridines
      by TDAE strategy starting from ortho- or para-nitro(dichloromethyl)benzene
      derivatives and N-tosylimines. A mixture of cis/trans isomers was isolated from 1
      (dichloromethyl)-4-nitrobenzene, whereas only trans-aziridines were obtained from
      ortho-nitro derivatives. 

PMID- 23884114
TI  - Ethanol extract of Atractylodes macrocephala protects bone loss by inhibiting
      osteoclast differentiation.
AB  - The rhizome of Atractylodes macrocephala has been used mainly in Traditional
      Chinese Medicine for invigorating the functions of the stomach and spleen. In the
      present study, we investigated the inhibitory effect of the 70% ethanol extract
      of the rhizome of Atractylodes macrocephala (AMEE) on osteoclast differentiation.
      We found that AMEE inhibits osteoclast differentiation from its precursors
      induced by receptor activator of nuclear factor-kappaB ligand (RANKL), an
      essential cytokine required for osteoclast differentiation. AMEE attenuated RANKL
      induced activation of NF-kappaB signaling pathway, subsequently inhibiting the
      induction of osteoclastogenic transcription factors, c-Fos and nuclear factor of
      activated T cells cytoplasmic 1. Consistent with the in vitro results,
      administration of AMEE protected RANKL-induced bone loss in mice. We also
      identified atractylenolide I and II as active constituents contributing to the
      anti-osteoclastogenic effect of AMEE. Taken together, our results demonstrate
      that AMEE has a protective effect on bone loss via inhibiting osteoclast
      differentiation and suggest that AMEE may be useful in preventing and treating
      various bone diseases associated with excessive bone resorption. 

PMID- 23884116
TI  - Hepatoprotective effects of mushrooms.
AB  - The particular characteristics of growth and development of mushrooms in nature
      result in the accumulation of a variety of secondary metabolites such as phenolic
      compounds, terpenes and steroids and essential cell wall components such as
      polysaccharides, b-glucans and proteins, several of them with biological
      activities. The present article outlines and discusses the available information
      about the protective effects of mushroom extracts against liver damage induced by
      exogenous compounds. Among mushrooms, Ganoderma lucidum is indubitably the most
      widely studied species. In this review, however, emphasis was given to studies
      using other mushrooms, especially those presenting efforts of attributing
      hepatoprotective activities to specific chemical components usually present in
      the mushroom extracts. 

PMID- 23884115
TI  - Modulation of xenobiotic receptors by steroids.
AB  - Nuclear receptors (NRs) are ligand-activated transcription factors that regulate
      the expression of their target genes. NRs play important roles in many human
      diseases, including metabolic diseases and cancer, and are therefore a key class
      of therapeutic targets. Steroids play important roles in regulating nuclear
      receptors; in addition to being ligands of steroid receptors, steroids (and their
      metabolites) also regulate other NRs, such as the pregnane X receptor and
      constitutive androstane receptor (termed xenobiotic receptors), which participate
      in steroid metabolism. Xenobiotic receptors have promiscuous ligand-binding
      properties, and their structurally diverse ligands include steroids and their
      metabolites. Therefore, steroids, their metabolism and metabolites, xenobiotic
      receptors, steroid receptors, and the respective signaling pathways they regulate
      have functional interactions. This review discusses these functional interactions
      and their implications for activities mediated by steroid receptors and
      xenobiotic receptors, focusing on steroids that modulate pathways involving the
      pregnane X receptor and constitutive androstane receptor. The emphasis of the
      review is on structure-function studies of xenobiotic receptors bound to steroid
      ligands. 

PMID- 23884117
TI  - Synthesis and characterization of some new complexes of magnesium (II) and zinc
      (II) with the natural flavonoid primuletin.
AB  - Two new metal complexes formulated as [Mg(L)2(H2O)2].H2O (1) and
      [Zn(L)2(H2O)2].0.5H2O (2), where HL = 5-hydroxyflavone (primuletin), have been
      synthesized and characterized by elemental and thermal analyses, molar
      conductance, IR, UV-Vis, 1H- and 13C-NMR, fluorescence and mass spectra. In solid
      state, complexes had shown higher fluorescence intensities comparing to the free
      ligand, and this behavior is appreciated as a consequence of the coordination
      process. 

PMID- 23884118
TI  - Eco-friendly chitosan production by Syncephalastrum racemosum and application to
      the removal of acid orange 7 (AO7) from wastewaters.
AB  - Due to the existence of new methodologies that have reduced the production costs
      of microbiological chitosan, this paper puts forward the use of agro-industrial
      residues in order to produce microbiological chitosan and to apply chitosan as an
      innovative resource for removing acid orange 7 (AO7) from wastewaters. The best
      culture conditions were selected by a full 24 factorial design, and the removal
      of the dye was optimized by a 23 central composite rotational design. The results
      showed that corn steep liquor (CSL) is an agro-industrial residue that can be
      advantageously used to produce microbiological chitosan with yields up to 7.8
      g/kg of substrate. FT-IR spectra of the product showed typical peak distributions
      like those of standard chitosan which confirmed the extracted product was
      chitosan-like. The efficiency of removing low concentrations of AO7 by using
      microbiological chitosan in distilled water (up to 89.96%) and tap water (up to
      80.60%) was significantly higher than the efficiency of the control (chitosan
      obtained from crustaceans), suggesting that this biopolymer is a better economic
      alternative for discoloring wastewater where a low concentration of the dye is
      considered toxic. The high percentage recovery of AO7 from the microbiological
      chitosan particles used favors this biopolymer as a possible bleaching agent
      which may be reusable. 

PMID- 23884119
TI  - 1,2,3-triazole-substituted oleanolic Acid derivatives: synthesis and
      antiproliferative activity.
AB  - Hybrid compounds are relevant products when searching for structure-activity
      relationships of natural products. Starting from the naturally occurring
      triterpene oleanolic acid, alkyl esters were prepared and treated with different
      aromatic azides using click chemistry to produce hybrid compounds. Some 18 new
      oleanolic acid derivatives were synthesized and the structures were confirmed by
      spectroscopic and spectrometric means. The antiproliferative activity of the new
      derivatives was evaluated towards normal lung fibroblasts (MRC-5), gastric
      epithelial adenocarcinoma (AGS), promyelocytic leukemia (HL-60), lung cancer (SK
      MES-1) and bladder carcinoma (J82) cells. The alkyne esters 1 and 3 showed
      activity on all cell lines but without selectivity (19.6-23.1 MUM and 14.1-56.2
      MUM, respectively), their respective methyl esters were inactive. Compounds with
      a benzene and p-anisole attached to the triazole ring, showed no
      antiproliferative effect. Introduction of a chlorine atom into the benzene ring
      (compound 9) elicited a selective effect against AGS cells (IC50 value: 8.9 MUM).
      The activity was lost when the COOH function at C-28 was methylated. Better
      antiproliferative effect was found for compounds 11 and 15 bearing a p
      toluenesulphonyl group, with values in the range of 10.8-47.1 MUM and 11.5-22.2
      MUM, respectively. The effect, however, was not associated with selectivity. 

PMID- 23884120
TI  - Efficient one-pot synthesis of 5-chloromethylfurfural (CMF) from carbohydrates in
      mild biphasic systems.
AB  - 5-Halomethylfurfurals can be considered as platform chemicals of high reactivity
      making them useful for the preparation of a variety of important compounds. In
      this study, a one-pot route for the conversion of carbohydrates into 5
      chloromethylfurfural (CMF) in a simple and efficient (HCl-H3PO4/CHCl3) biphasic
      system has been investigated. Monosaccharides such as D-fructose, D-glucose and
      sorbose, disaccharides such as sucrose and cellobiose and polysaccharides such as
      cellulose were successfully converted into CMF in satisfactory yields under mild
      conditions. Our data shows that when using D-fructose the optimum yield of CMF
      was about 47%. This understanding allowed us to extent our work to biomaterials,
      such as wood powder and wood pulps with yields of CMF obtained being comparable
      to those seen with some of the enumerated mono and disaccharides. Overall, the
      proposed (HCl-H3PO4/CHCl3) optimized biphasic system provides a simple, mild, and
      cost-effective means to prepare CMF from renewable resources. 

PMID- 23884121
TI  - Biosynthesis of panaxynol and panaxydol in Panax ginseng.
AB  - The natural formation of the bioactive C17-polyacetylenes (-)-(R)-panaxynol and
      panaxydol was analyzed by 13C-labeling experiments. For this purpose, plants of
      Panax ginseng were supplied with 13CO2 under field conditions or, alternatively,
      sterile root cultures of P. ginseng were supplemented with [U-13C6]glucose. The
      polyynes were isolated from the labeled roots or hairy root cultures,
      respectively, and analyzed by quantitative NMR spectroscopy. The same mixtures of
      eight doubly 13C-labeled isotopologues and one single labeled isotopologue were
      observed in the C17-polyacetylenes obtained from the two experiments. The
      polyketide-type labeling pattern is in line with the biosynthetic origin of the
      compounds via decarboxylation of fatty acids, probably of crepenynic acid. The
      13C-study now provides experimental evidence for the biosynthesis of panaxynol
      and related polyacetylenes in P. ginseng under in planta conditions as well as in
      root cultures. The data also show that 13CO2 experiments under field conditions
      are useful to elucidate the biosynthetic pathways of metabolites, including those
      from roots. 

PMID- 23884122
TI  - Protection of astaxanthin in astaxanthin nanodispersions using additional
      antioxidants.
AB  - The protective effects of alpha-tocopherol and ascorbic acid on astaxanthin in
      astaxanthin nanodispersions produced via a solvent-diffusion technique and
      stabilized by a three-component stabilizer system, were studied either
      individually or in combination by using response surface methodology. Generally,
      both alpha-tocopherol and ascorbic acid could retard the astaxanthin degradation
      in astaxanthin nanodispersions. The results showed that the using alpha
      tocopherol and ascorbic acid can be more efficient in increasing the chemical
      stability of nanodispersions in comparison to using them individually. Using a
      response surface methodology (RSM) response optimizer, it was seen that addition
      of ascorbic acid (ascorbic acid/astaxanthin w/w) and alpha-tocopherol (alpha
      tocopherol/astaxanthin w/w) in proportions of 0.4 and 0.6, respectively, would
      give the maximum chemical stability to the studied astaxanthin nanodispersions. 

PMID- 23884123
TI  - In vitro antimicrobial activity of plant-derived diterpenes against bovine
      mastitis bacteria.
AB  - We evaluated the antibacterial activity of three diterpenes isolated from natural
      sources against a panel of microorganisms responsible for bovine mastitis. ent
      Copalic acid (CA) was the most active metabolite, with promising MIC values (from
      1.56 to 6.25 ug mL-1) against Staphylococcus aureus (ATCC and clinical isolate),
      Staphylococcus epidermidis, Streptococcus agalactiae, and Streptococcus
      dysgalactiae. We conducted time-kill assays of CA against S. aureus, a commensal
      organism considered to be a ubiquitous etiological agent of bovine mastitis in
      dairy farms worldwide. In the first 12 h, CA only inhibited the growth of the
      inoculums (bacteriostatic effect), but its bactericidal effect was clearly noted
      thereafter (between 12 and 24 h). In conclusion, CA should be considered for the
      control of several Gram-positive bacteria related to bovine mastitis. 

PMID- 23884124
TI  - Comprehensive theoretical studies on the reaction of 1-bromo-3,3,3
      trifluoropropene with OH free radicals.
AB  - The potential energy surfaces (PES) for the reaction of 1-bromo-3,3,3
      trifluoropropene (CF3CHCBrH) with hydroxyl (OH) free radicals is probed
      theoretically at the CCSD/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of theory. All
      the possible stationary and first-order saddle points along the reaction paths
      were verified by the vibrational analysis. The calculations account for all the
      product channels. Based on the calculated CCSD/aug-cc-pVDZ potential energy
      surface, the possible reaction mechanism is discussed. Six distinct reaction
      pathways of 1-bromo-3,3,3-trifluoropropene (BTP) with OH are investigated. The
      geometries, reaction enthalpies and energy barriers are determined. Canonical
      transition-state theory with Wigner tunneling correction was used to predict the
      rate constants for the temperature range of 290-3,000 K without any artificial
      adjustment, and the computed rate constants for elementary channels can be
      accurately fitted with three-parameter Arrhenius expressions. OH addition
      reaction channel and the H atom abstraction channels related to the carbon-carbon
      double bond are found to be the main reaction channels for the reaction of 1
      bromo-3,3,3-trifluoropropene (CF3CHCBrH) with hydroxyl (OH) free radicals while
      the products leading to CF3CHCH + BrOH and COHF2CHCBrH + F play a negligible
      role. 

PMID- 23884125
TI  - Triterpenoids of marine origin as anti-cancer agents.
AB  - Triterpenoids are the most abundant secondary metabolites present in marine
      organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived
      fungi. A large number of triterpenoids are known to exhibit cytotoxicity against
      a variety of tumor cells, as well as anticancer efficacy in preclinical animal
      models. In this review efforts have been taken to review the structural features
      and the potential use of triterpenoids of marine origin to be used in the
      pharmaceutical industry as potential anti-cancer drug leads. 

PMID- 23884126
TI  - Retraction. Hashim, H. et al., Cytoprotective effect of benzyl N'-(5-chloro-indol
      3-yl-methylidene)hydrazinecarbodithioate against ethanol-induced gastric mucosal
      injury in rats. Molecules 2012, 17, 9306-9320.

PMID- 23884127
TI  - Dendrimers as potential therapeutic tools in HIV inhibition.
AB  - The present treatments for HIV transfection include chemical agents and gene
      therapies. Although many chemical drugs, peptides and genes have been developed
      for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency
      of these materials. In this review, we discuss the application of dendrimers as
      both therapeutic agents and non-viral vectors of chemical agents and genes for
      HIV treatment. On the one hand, dendrimers with functional end groups combine
      with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of
      HIV to the host cell. Some of the dendrimers are capable of intruding into the
      cell and interfere with the later stages of HIV replication as well. On the other
      hand, dendrimers are also able to transfer chemical drugs and genes into the host
      cells, which conspicuously increase the anti-HIV activity of these materials.
      Dendrimers as therapeutic tools provide a potential treatment for HIV infection. 

PMID- 23884128
TI  - Microfluidics: a groundbreaking technology for PET tracer production?
AB  - Application of microfluidics to Positron Emission Tomography (PET) tracer
      synthesis has attracted increasing interest within the last decade. The technical
      advantages of microfluidics, in particular the high surface to volume ratio and
      resulting fast thermal heating and cooling rates of reagents can lead to reduced
      reaction times, increased synthesis yields and reduced by-products. In addition
      automated reaction optimization, reduced consumption of expensive reagents and a
      path towards a reduced system footprint have been successfully demonstrated. The
      processing of radioactivity levels required for routine production, use of
      microfluidic-produced PET tracer doses in preclinical and clinical imaging as
      well as feasibility studies on autoradiolytic decomposition have all given
      promising results. However, the number of microfluidic synthesizers utilized for
      commercial routine production of PET tracers is very limited. This study reviews
      the state of the art in microfluidic PET tracer synthesis, highlighting critical
      design aspects, strengths, weaknesses and presenting several characteristics of
      the diverse PET market space which are thought to have a significant impact on
      research, development and engineering of microfluidic devices in this field.
      Furthermore, the topics of batch- and single-dose production, cyclotron to
      quality control integration as well as centralized versus de-centralized market
      distribution models are addressed. 

PMID- 23884129
TI  - Abscisic acid induced changes in production of primary and secondary metabolites,
      photosynthetic capacity, antioxidant capability, antioxidant enzymes and
      lipoxygenase inhibitory activity of Orthosiphon stamineus Benth.
AB  - An experiment was conducted to investigate and distinguish the relationships in
      the production of total phenolics, total flavonoids, soluble sugars, H2O2, O2-,
      phenylalanine ammonia lyase (PAL) activity, leaf gas exchange, antioxidant
      activity, antioxidant enzyme activity [ascorbate peroxidase (APX), catalase
      (CAT), superoxide dismutase (SOD) and Lipoxygenase inhibitory activity (LOX)]
      under four levels of foliar abscisic acid (ABA) application (0, 2, 4, 6 uM) for
      15 weeks in Orthosiphon stamineus Benth. It was found that the production of
      plant secondary metabolites, soluble sugars, antioxidant activity, PAL activity
      and LOX inhibitory activity was influenced by foliar application of ABA. As the
      concentration of ABA was increased from 0 to 6 uM the production of total
      phenolics, flavonoids, sucrose, H2O2, O2-, PAL activity and LOX inhibitory
      activity was enhanced. It was also observed that the antioxidant capabilities
      (DPPH and ORAC) were increased. This was followed by increases in production of
      antioxidant enzymes APX, CAT and SOD. Under high application rates of ABA the net
      photosynthesis and stomatal conductance was found to be reduced. The production
      of primary and secondary metabolites displayed a significant positive
      relationship with H2O2 (total phenolics, r2 = 0.877; total flavonoids, r2 =
      0.812; p <= 0.05) and O2- (total phenolics, r2 = 0.778; total flavonoids, r2 =
      0.912; p <= 0.05). This indicated that increased oxidative stress at high
      application rates of ABA, improved the production of phytochemicals. 

PMID- 23884130
TI  - Antibacterial and herbicidal activity of ring-substituted 3-hydroxynaphthalene-2
      carboxanilides.
AB  - In this study, a series of twenty-two ring-substituted 3-hydroxy-N
      phenylnaphthalene-2-carboxanilides were prepared and characterized. The compounds
      were tested for their activity related to inhibition of photosynthetic electron
      transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro
      screening of the synthesized compounds was also performed against four
      Staphylococcus strains and against two mycobacterial species. 3-Hydroxy-N-(2
      methoxyphenyl)naphthalene-2-carboxamide showed high biological activity (MIC =
      55.0 umol/L) against S. aureus as well as methicillin-resistant strains. N-(2
      Fluorophenyl)-3-hydroxynaphthalene-2-carboxamide showed higher activity (MIC =
      28.4 umol/L) against M. marinum than the standard isoniazid and 3-hydroxy-N-(4
      nitrophenyl)naphthalene-2-carboxamide expressed higher activity (MIC = 13.0
      umol/L) against M. kansasii than the standard isoniazid. Cytotoxicity assay of
      effective antimicrobial compounds was performed using the human monocytic
      leukemia THP-1 cell line. The PET-inhibiting activity expressed by IC50 value of
      the most active compound 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide was
      16.9 MUmol/L. The structure-activity relationships of all compounds are
      discussed. 

PMID- 23884131
TI  - Preventive effects of Eleutherococcus senticosus bark extract in OVX-induced
      osteoporosis in rats.
AB  - Eleutherococcus senticosus (Siberian ginseng), has been used as a powerful tonic
      herb with an impressive range of health benefits. This medicinal herb has been
      commonly used to treat bone metabolism diseases due to its traditional Korean
      medicine use to strengthen muscle and bone. This study was conducted to
      investigate prevention of bone loss by a standardized extract of dried E.
      senticosus stem bark in an ovariectomized (OVX) rat model of osteoporosis. The
      OVX groups were divided into five groups treated with distilled water, 17beta
      estradiol (E2 10 MUg/kg, once daily, i.p) and dried stem bark of E. senticosus
      extracts (DES 10, 30, and 100 mg/kg, once daily, p.o) for eight weeks,
      respectively. After eight weeks of treatments, the femur bone mineral density of
      the 100 mg/kg DES-treated group was significantly higher than that of the OVX
      control group (16.7%, p < 0.01) without affecting the body, organs, and uterus
      weights, and serum estradiol levels. Additionally, bone markers such as serum
      ALP, CTx, and OC levels were significantly decreased in the DES 100 mg/kg treated
      group. These results show that DES is able to prevent OVX-induced in bone loss
      without the influence of hormones such as estrogen. 

PMID- 23884132
TI  - Antiplasmodial alkaloids from the bark of Cryptocarya nigra (Lauraceae).
AB  - A dichloromethane extract of the stem bark of Cryptocarya nigra showed strong in
      vitro inhibition of Plasmodium falciparum growth, with an IC50 value of 2.82
      MUg/mL. The phytochemical study of this extract has led to the isolation and
      characterization of four known alkaloids: (+)-N-methylisococlaurine (1),
      atherosperminine (2), 2-hydroxyathersperminine (3), and noratherosperminine (4).
      Structural elucidation of all alkaloids was accomplished by means of high field
      1D- and 2D-NMR, IR, UV and LCMS spectral data. The isolated extract constituents
      (+)-N-methylisococlaurine (1), atherosperminine (2) and 2-hydroxy
      atherosperminine (3) showed strong antiplasmodial activity, with IC50 values of
      5.40, 5.80 and 0.75 MUM, respectively. In addition, (+)-N-methylisocolaurine (1)
      and atherosperminine (2) showed high antioxidant activity in a DPPH assay with
      IC50 values of 29.56 ug/mL and 54.53 ug/mL respectively. Compounds 1 and 2 also
      both showed high antioxidant activity in the FRAP assay, with percentages of
      78.54 and 70.66 respectively and in the metal chelating assay, with IC50 values
      of 50.08 ug/mL and 42.87 ug/mL, respectively. 

PMID- 23884133
TI  - Synthesis and preliminary biological evaluations of 5'-substituted derivatives of
      uridine as glycosyltransferase inhibitors.
AB  - New derivatives of uridine which contain a b-ketoenol motif were synthesized,
      characterized and biologically tested. Synthesized compounds 1-4 showed no
      activity against bovine milk beta-1,4-galactosyltransferase I at concentrations
      up to 2.0 mM and were not active against Candida albicans and Aspergilus
      fumigatus up to the maximum tested concentration of 1,000 ug/mL. 

PMID- 23884134
TI  - Mechanistic studies on regioselective dephosphorylation of phosphate prodrugs
      during a facile synthesis of antitumor phosphorylated 2-phenyl-6,7-methylenedioxy
      1H-quinolin-4-one.
AB  - Phosphorylation of 2-(3-hydroxy-5-methoxyphenyl)-6,7-methylenedioxy-1H-quinolin-4
      one (1) afforded diphosphate 2. We found that, upon treatment with methanol under
      mild conditions, 2 can undergo facile and highly regioselective dephosphorylation
      to give the monophosphate 3, with a phosphate group remaining on the phenyl ring.
      The details of the dephosphorylation process were postulated and then probed by
      LC-MS and HPLC analyses. Furthermore, as a preliminary study, the water soluble
      monophosphate prodrug 4 was tested for antitumor activity against a MCF-7
      xenograft nude mice model. 

PMID- 23884135
TI  - Synthesis of new cytotoxic aminoanthraquinone derivatives via nucleophilic
      substitution reactions.
AB  - Aminoanthraquinones were successfully synthesized via two reaction steps. 1,4
      Dihydroxyanthraquinone (1) was first subjected to methylation, reduction and
      acylation to give an excellent yield of anthracene-1,4-dione (3), 1,4
      dimethoxyanthracene-9,10-dione (5) and 9,10-dioxo-9,10-dihydroanthracene-1,4-diyl
      diacetate (7). Treatment of 1, 3, 5 and 7 with BuNH2 in the presence of PhI(OAc)2
      as catalyst produced seven aminoanthraquinone derivatives 1a, b, 3a, and 5a-d.
      Amination of 3 and 5 afforded three new aminoanthraquinones, namely 2
      (butylamino)anthracene-1,4-dione (3a), 2-(butylamino)anthracene-9,10-dione (5a)
      and 2,3-(dibutylamino)anthracene-9,10-dione (5b). All newly synthesised
      aminoanthraquinones were examined for their cytotoxic activity against MCF-7
      (estrogen receptor positive human breast) and Hep-G2 (human hepatocellular liver
      carcinoma) cancer cells using MTT assay. Aminoanthraquinones 3a, 5a and 5b
      exhibited strong cytotoxicity towards both cancer cell lines (IC50 1.1-13.0
      ug/mL). 

PMID- 23884136
TI  - In-solution conformational analysis of the XCYCH3 moiety for small esters and
      ethers with all combinations of X, Y = O, S.
AB  - Favorable steric and electrostatic fit of a ligand to a receptor is of central
      interest in theoretical drug design. This paper considers the effects of non
      protic solvents, in comparison with the gas phase, on the preferred conformation
      of the XCYCH3 moiety of simple aliphatic esters and heterocyclic methyl ethers
      with all combinations of the X and Y atoms as oxygen and sulfur. An IEF
      PCM/B97D/aug-cc-pv(t+d)z continuum dielectric solvent study in chloroform and
      acetonitrile explores the through-space polarization effect of the environment on
      the conformational preference, not affected by possible solute-solvent hydrogen
      bond formation. The inherently favored structure for the present molecules is
      important, since the hypothetical oxygen and sulfur lone-pairs point
      approximately in opposite directions in the cis conformation of esters, whereas
      the trans and gauche conformations for the methyl group in ethers define nearly
      parallel or perpendicular directionality for the lone pairs of the ring
      heteroatoms and the O or S atoms connecting to the ring. These different
      preferences for the studied two families of compounds allow for designing
      formation of hydrogen bonds with a protein in fairly different regions of the
      latter still within the ligand-binding cavity. For a fine-tuning of these
      hydrogen bonds, a replacement of an oxygen atom of the ligand by a sulfur atom
      could be a straightforward possibility. 

PMID- 23884137
TI  - Whole body acid-base and fluid-electrolyte balance: a mathematical model.
AB  - A cellular compartment was added to our previous mathematical model of steady
      state acid-base and fluid-electrolyte chemistry to gain further understanding and
      aid diagnosis of complex disorders involving cellular involvement in critically
      ill patients. An important hypothesis to be validated was that the thermodynamic,
      standard free-energy of cellular H(+) and Na(+) pumps remained constant under all
      conditions. In addition, a hydrostatic-osmotic pressure balance was assumed to
      describe fluid exchange between plasma and interstitial fluid, including
      incorporation of compliance curves of vascular and interstitial spaces. The
      description of the cellular compartment was validated by close comparison of
      measured and model-predicted cellular pH and electrolyte changes in vitro and in
      vivo. The new description of plasma-interstitial fluid exchange was validated
      using measured changes in fluid volumes after isoosmotic and hyperosmotic fluid
      infusions of NaCl and NaHCO3. The validated model was used to explain the role of
      cells in the mechanism of saline or dilutional acidosis and acid-base effects of
      acidic or basic fluid infusions and the acid-base disorder due to potassium
      depletion. A module was created that would allow users, who do not possess the
      software, to determine, for free, the results of fluid infusions and urinary
      losses of water and solutes to the whole body. 

PMID- 23884138
TI  - Beware the low HDAC11: males at risk for ischemic kidney injury.

PMID- 23884139
TI  - Albuminuria induces a proinflammatory and profibrotic response in cortical
      collecting ducts via the 24p3 receptor.
AB  - Albuminuria is strongly associated with progressive kidney tubulo-interstitial
      damage and chronic kidney disease (CKD) progression. In proteinuric
      nephropathies, albumin reabsorption by the proximal tubule is saturated and the
      distal nephron is exposed to high concentrations of luminal albumin that may
      produce adverse effects. Since proximal tubular cells exposed to albuminuria
      exhibit a proinflammatory and profibrotic response, we assessed the effect of
      albuminuria in the collecting duct (CD). With the use of kidney sections and
      isolated cortical CDs (CCDs) from puromycin-aminonucleoside-induced nephrotic
      rats (PAN rats) exhibiting proteinuria, immunofluorescence microscopy revealed
      internalized albumin in CD cells. In these proteinuric rats, increased expression
      levels of cytokines and profibrotic signaling markers were detected in isolated
      CCDs and bands of inflammatory fibrosis could be observed around CDs. Albumin
      endocytosis was confirmed by FITC-albumin uptake in cultured murine CCD (mCCDcl1)
      cells. Exposure of mCCDcl1 cells to albumin induced NF-kappaB activation as
      assessed by luciferase reporter gene assay, nuclear translocation of NF-kappaB
      p65 subunit, and increased NF-kappaB target gene expression. Moreover,
      albuminuria-like condition results in transforming growth factor-beta1 (TGF
      beta1) overexpression and the upregulation of profibrotic signaling markers such
      as Snail or vimentin via an autocrine mechanism. In mCCDcl1 cells, neutrophil
      gelatinase-associated lipocalin (NGAL)/lipocalin-2/24p3 receptor (24p3R) mediates
      albumin endocytosis as well as activation of NF-kappaB and TGF-beta1 signaling
      pathways. Therefore, CD may play a key role in initiation and/or progression of
      inflammation and fibrosis in response to proteinuria.

PMID- 23884140
TI  - Protective role of small pigment epithelium-derived factor (PEDF) peptide in
      diabetic renal injury.
AB  - Pigment epithelium-derived factor (PEDF) is a multifunctional protein with
      antiangiogenic, antioxidative, and anti-inflammatory properties. PEDF is involved
      in the pathogenesis of diabetic retinopathy, but its direct role in the kidneys
      remains unclear. We hypothesize that a PEDF fragment (P78-PEDF) confers kidney
      protection in diabetic nephropathy (DN). The localization of the full-length PEDF
      protein were determined in DBA mice following multiple low doses of
      streptozotocin. Using immunohistochemistry, PEDF was localized in the kidney
      vasculature, interstitial space, glomeruli, tubules, and renal medulla. Kidney
      PEDF protein and mRNA expression were significantly reduced in diabetic mice.
      Continuous infusion of P78-PEDF for 6 wk resulted in protection from diabetic
      neuropathy as indicated by reduced albuminuria and blood urea nitrogen, increased
      nephrin expression, decreased kidney macrophage recruitment and inflammatory
      cytokines, and reduced histological changes compared with vehicle-treated
      diabetic mice. In vitro, P78-PEDF blocked the increase in podocyte permeability
      to albumin and disruption of the actin cytoskeleton induced by puromycin
      aminonucleoside treatment. These findings highlight the importance of P78-PEDF
      peptide as a potential therapeutic modality in early phase diabetic renal injury.

PMID- 23884141
TI  - CXCR4-overexpressing bone marrow-derived mesenchymal stem cells improve repair of
      acute kidney injury.
AB  - Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) can repair
      acute kidney injury (AKI), but with limited effect. We test the hypothesis that
      CXCR4 overexpression improves the repair ability of BMSCs and that this is
      related to increased homing of BMSCs and increased release of cytokines.
      Hypoxia/reoxygenation-pretreated renal tubular epithelial cells (HR-RTECs) were
      used. BMSCs, null-BMSCs, and CXCR4-BMSCs were cocultured with HR-RTECs. The
      number of migrating BMSCs was counted. Proliferating cell nuclear antigen (PCNA)
      expression, cell death, and expressions of cleaved caspase-3 and Bcl-2 in
      cocultured HR-RTECs were measured. Cytokeratin 18 (CK18) expression and cytokine
      secretions of the BMSCs cultured with HR-RTEC supernatant were detected. BMSC
      homing, renal function, proliferation, and cell death of tubular cells were
      assayed in the AKI mouse model. CXCR4-BMSCs showed a remarkable expression of
      CXCR4. Stromal cell-derived factor-1 in the HR-RTEC supernatant was increased.
      Migration of BMSCs was CXCR4-dependent. Proportions of CK18(+) cells in BMSCs,
      null-BMSCs, and CXCR4-BMSCs showed no difference. However, CXCR4 overexpression
      in BMSCs stimulated secretion of bone morphogenetic protein-7, hepatocyte growth
      factor, and interleukin 10. The neutralizing anti-CXCR4 antibody AMD3100
      abolished this. In cocultured HR-RTECs the proportions of PCNA(+) cells and Bcl-2
      expression were enhanced; however, the proportion of annexin V(+) cells and
      expression of cleaved caspase-3 were reduced. The in vivo study showed increased
      homing of CXCR4-BMSCs in kidneys, which was associated with improved renal
      function, reduced acute tubular necrosis scoring, accelerated mitogenic response
      of tubular cells, and reduced tubular cell death. The enhanced homing and
      paracrine actions of BMSCs with CXCR4 overexpression suggest beneficial effects
      of such cells in BMSC-based therapy for AKI.

PMID- 23884142
TI  - Adenosine inhibits renin release from juxtaglomerular cells via an A1 receptor
      TRPC-mediated pathway.
AB  - Renin is synthesized and released from juxtaglomerular (JG) cells. Adenosine
      inhibits renin release via an adenosine A1 receptor (A1R) calcium-mediated
      pathway. How this occurs is unknown. In cardiomyocytes, adenosine increases
      intracellular calcium via transient receptor potential canonical (TRPC) channels.
      We hypothesized that adenosine inhibits renin release via A1R activation, opening
      TRPC channels. However, higher concentrations of adenosine may stimulate renin
      release through A2R activation. Using primary cultures of isolated mouse JG
      cells, immunolabeling demonstrated renin and A1R in JG cells, but not A2R
      subtypes, although RT-PCR indicated the presence of mRNA of both A2AR and A2BR.
      Incubating JG cells with increasing concentrations of adenosine decreased renin
      release. Different concentrations of the adenosine receptor agonist N
      ethylcarboxamide adenosine (NECA) did not change renin. Activating A1R with 0.5
      MUM N6-cyclohexyladenosine (CHA) decreased basal renin release from 0.22 +/- 0.05
      to 0.14 +/- 0.03 MUg of angiotensin I generated per milliliter of sample per hour
      of incubation (AngI/ml/mg prot) (P < 0.03), and higher concentrations also
      inhibited renin. Reducing extracellular calcium with EGTA increased renin release
      (0.35 +/- 0.08 MUg AngI/ml/mg prot; P < 0.01), and blocked renin inhibition by
      CHA (0.28 +/- 0.06 MUg AngI/ml/mg prot; P < 0. 005 vs. CHA alone). The
      intracellular calcium chelator BAPTA-AM increased renin release by 55%, and
      blocked the inhibitory effect of CHA. Repeating these experiments in JG cells
      from A1R knockout mice using CHA or NECA demonstrated no effect on renin release.
      However, RT-PCR showed mRNA from TRPC isoforms 3 and 6 in isolated JG cells.
      Adding the TRPC blocker SKF-96365 reversed CHA-mediated inhibition of renin
      release. Thus A1R activation results in a calcium-dependent inhibition of renin
      release via TRPC-mediated calcium entry, but A2 receptors do not regulate renin
      release. 

PMID- 23884144
TI  - Renal anemia: from incurable to curable.
AB  - Renal anemia has been recognized as a characteristic complication of chronic
      kidney disease. Although many factors are involved in renal anemia, the
      predominant cause of renal anemia is a relative deficiency in erythropoietin
      (EPO) production. To date, exogenous recombinant human (rh)EPO has been widely
      used as a powerful drug for the treatment of patients with renal anemia. Despite
      its clinical effectiveness, a potential risk for increased mortality has been
      suggested in patients who receive rhEPO, in addition to the economic burden of
      rhEPO administration. The induction of endogenous EPO is another therapeutic
      approach that might have advantages over rhEPO administration. However, the
      physiological and pathophysiological regulation of EPO are not fully understood,
      and this lack of understanding has hindered the development of an endogenous EPO
      inducer. In this review, we will discuss the current treatment for renal anemia
      and its drawbacks, provide an overview of EPO regulation in healthy and diseased
      conditions, and propose future directions for therapeutic trials that more
      directly target the underlying pathophysiology of renal anemia.

PMID- 23884143
TI  - Thromboxane-induced renal vasoconstriction is mediated by the ADP-ribosyl cyclase
      CD38 and superoxide anion.
AB  - The present renal hemodynamic study tested the hypothesis that CD38 and
      superoxide anion (O2(.-)) participate in the vasoconstriction produced by
      activation of thromboxane prostanoid (TP) receptors in the mouse kidney. CD38 is
      the major mammalian ADP-ribosyl cyclase contributing to vasomotor tone through
      the generation of cADP-ribose, a second messenger that activates ryanodine
      receptors to release Ca(2+) from the sarcoplasmic reticulum in vascular smooth
      muscle cells. We evaluated whether the stable thromboxane mimetic U-46619 causes
      less pronounced renal vasoconstriction in CD38-deficient mice and the involvement
      of O2(.-) in U-46619-induced renal vasoconstriction. Our results indicate that U
      46619 activation of TP receptors causes renal vasoconstriction in part by
      activating cADP-ribose signaling in renal resistance arterioles. Based on maximal
      renal blood flow and renal vascular resistance responses to bolus injections of U
      46619, CD38 contributes 30-40% of the TP receptor-induced vasoconstriction. We
      also found that the antioxidant SOD mimetic tempol attenuated the magnitude of
      vasoconstriction by U-46619 in both groups of mice, suggesting mediation by O2(.
      ). The degree of tempol blockage of U-46619-induced renal vasoconstriction was
      greater in wild-type mice, attenuating renal vasoconstriction by 40% compared
      with 30% in CD38-null mice. In other experiments, U-46619 rapidly stimulated O2(.
      ) production (dihydroethidium fluorescence) in isolated mouse afferent
      arterioles, an effect abolished by tempol. These observations provide the first
      in vivo demonstration of CD38 and O2(.-) involvement in the vasoconstrictor
      effects of TP receptor activation in the kidney and in vitro evidence for TP
      receptor stimulation of O2(.-) production by the afferent arteriole. 

PMID- 23884145
TI  - Bladder filling and voiding affect umbrella cell tight junction organization and
      function.
AB  - Epithelial cells are continuously exposed to mechanical forces including shear
      stress and stretch, although the effect these forces have on tight junction (TJ)
      organization and function are poorly understood. Umbrella cells form the
      outermost layer of the stratified uroepithelium and undergo large cell shape and
      surface area changes during the bladder cycle. Here we investigated the effects
      of bladder filling and voiding on the umbrella cell TJ. We found that bladder
      filling promoted a significant increase in the length of the TJ ring, which was
      quickly reversed within 5 min of voiding. Interestingly, when isolated
      uroepithelial tissue was mounted in Ussing chambers and exposed to physiological
      stretch, we observed a 10-fold drop in both transepithelial electrical resistance
      (TER) and the umbrella cell junctional resistance. The effects of stretch on TER
      were reversible and dependent on the applied force. Furthermore, the integrity of
      the umbrella cell TJ was maintained in the stretched uroepithelium, as suggested
      by the limited permeability of biotin, fluorescein, and ruthenium red. Finally,
      we found that depletion of extracellular Ca(2+) by EGTA completely disrupted the
      TER of unstretched, but not of stretched uroepithelium. Taken together, our
      studies indicate that the umbrella cell TJ undergoes major structural and
      functional reorganization during the bladder cycle. The impact of these changes
      on bladder function is discussed. 

PMID- 23884146
TI  - Measurement of glomerular filtration rate during flight in a migratory bird using
      a single bolus injection of FITC-inulin.
AB  - During migration, passerine birds typically complete a series of multi-hour
      flights, each followed by a period of stopover. During flight, rates of
      respiratory water loss are high, yet these birds show no signs of dehydration
      after flights. During stopover, birds become hyperphagic to replenish fat
      reserves, often consuming food with high water content, such as fruit. Thus
      migratory birds seem to face an osmoregulatory challenge; they must reduce water
      losses during flight but retain the ability to excrete large quantities of water
      while maintaining osmotic balance at stopover. Our goal was to measure glomerular
      filtration rate (GFR) and fractional water reabsorption (FWR) of a migratory bird
      in free flight, at rest, and during feeding to assess the role of the kidney in
      maintaining water balance during migration. We used FITC-inulin and one- and two
      phase exponential decay models to first validate a technique and then measure GFR
      in the Swainson's thrush, a small (~30 g) songbird. Single-phase exponential
      decay models and the modified slope intercept method overestimated GFR by 26%
      compared with two-phase exponential decay models. We found no differences in GFR
      among fed, resting and flying birds, but FWR was significantly higher in resting
      and flying birds relative to feeding birds. There was no effect of the rate of
      respiratory water loss on GFR or FWR in flight. These data support the idea that
      birds in flight do not dramatically alter GFR but rely on increased FWR to
      minimize excretory water losses. 

PMID- 23884147
TI  - Injured kidney endothelium is only marginally repopulated by cells of extrarenal
      origin.
AB  - The role of bone marrow marrow-derived cells after kidney endothelial injury is
      controversial. In this study, we investigated if and to what extent extrarenal
      cells incorporate into kidney endothelium after acute as well as during chronic
      endothelial injury. Fischer F-344wt (wild type) rat kidney grafts were
      transplanted into R26-hPAP (human placental alkaline phosphatase) transgenic
      Fischer F-344 recipient rats to allow identification of extrarenal cells by
      specific antibody staining. A severe model of renal thrombotic microangiopathy
      was induced via graft perfusion with antiglomerular endothelial cell (GEN)
      antibody and resulted in eradication of 85% of the glomerular and 69% of the
      peritubular endothelium (GEN group). At week 4 after injury, renal endothelial
      healing as well as recovery of the kidney function was seen. Endothelial
      chimerism was evaluated by double staining for hPAP and endothelial markers RECA
      1 or JG-12. Just 0.25% of the glomerular and 0.1% of the peritubular endothelium
      was recipient derived. In a second experiment, chronic endothelial injury was
      induced by combination of kidney transplantation with 5/6 nephrectomy (5/6 Nx
      group). After 14 wk, only 0.86% of the peritubular and 0.05% of the glomerular
      endothelium was of recipient origin. In summary, despite demonstration of
      extensive damage and loss as well as excellent regeneration, just a minority of
      extrarenal cells were incorporated into kidney endothelium in rat models of acute
      and chronic renal endothelial cell injury. Our results highlight that kidney
      endothelial regeneration after specific and severe injury is almost exclusively
      of renal origin.

PMID- 23884148
TI  - Rapamycin inhibition of mTORC1 reverses lithium-induced proliferation of renal
      collecting duct cells.
AB  - Nephrogenic diabetes insipidus (NDI) is the most common renal side effect in
      patients undergoing lithium therapy for bipolar affective disorders.
      Approximately 2 million US patients take lithium of whom ~50% will have altered
      renal function and develop NDI (2, 37). Lithium-induced NDI is a defect in the
      urinary concentrating mechanism. Lithium therapy also leads to proliferation and
      abundant renal cysts (microcysts), commonly in the collecting ducts of the
      cortico-medullary region. The mTOR pathway integrates nutrient and mitogen
      signals to control cell proliferation and cell growth (size) via the mTOR Complex
      1 (mTORC1). To address our hypothesis that mTOR activation may be responsible for
      lithium-induced proliferation of collecting ducts, we fed mice lithium
      chronically and assessed mTORC1 signaling in the renal medulla. We demonstrate
      that mTOR signaling is activated in the renal collecting ducts of lithium-treated
      mice; lithium increased the phosphorylation of rS6 (Ser240/Ser244), p-TSC2
      (Thr1462), and p-mTOR (Ser2448). Consistent with our hypothesis, treatment with
      rapamycin, an allosteric inhibitor of mTOR, reversed lithium-induced
      proliferation of medullary collecting duct cells and reduced levels of p-rS6 and
      p-mTOR. Medullary levels of p-GSK3beta were increased in the renal medullas of
      lithium-treated mice and remained elevated following rapamycin treatment.
      However, mTOR inhibition did not improve lithium-induced NDI and did not restore
      the expression of collecting duct proteins aquaporin-2 or UT-A1. 

PMID- 23884150
TI  - Eltrombopag-associated hyperpigmentation.

PMID- 23884149
TI  - Loss of deep cerebellar nuclei neurons in the 3xTg-AD mice and protection by an
      anti-amyloid beta antibody fragment.
AB  - The therapeutic potential of scFv-h3D6 has recently been shown in the 3xTg-AD
      mice. A clear effect on amyloid beta (Abeta) oligomers and certain
      apolipoproteins in the brain was found, but no effect was seen in the cerebellum.
      Here, cellular vulnerability of the 3xTg-AD cerebellum is described for the first
      time, together with its protection by scFv-h3D6. Neuron depletion in the DCN was
      regionally variable and followed a mediolateral axis of involvement that was
      greatest in the fastigial nucleus, lesser in the interpositus and negligible in
      the dentate nucleus. A sole and low intraperitoneal dose of scFv-h3D6 protected
      3xTg-AD DCN neurons from death. Further studies might provide interesting
      information about both the potential of scFv-h3D6 as a therapeutic agent and the
      role of the cerebellum in AD. 

PMID- 23884151
TI  - The SCN1A gene variants and epileptic encephalopathies.
AB  - The voltage-gated sodium channels are fundamental units that evoke the action
      potential in excitable cells such as neurons. These channels are integral
      membrane proteins typically consisting of one alpha-subunit, which forms the
      larger central pore of the channel, and two smaller auxiliary beta-subunits,
      which modulate the channel functions. Genetic alterations in the SCN1A gene
      coding for the alpha-subunit of the neuronal voltage-gated sodium ion channel,
      type 1 (NaV 1.1), is associated with a spectrum of seizure-related disorders in
      human, ranging from a relatively milder form of febrile seizures to a more severe
      epileptic condition known as the Dravet syndrome. Among the epilepsy genes, the
      SCN1A gene perhaps known to have the largest number of disease-associated
      alleles. Here we present a meta-analysis on the SCN1A gene variants and provide
      comprehensive information on epilepsy-associated gene variants, their frequency,
      the predicted effect on the protein, the ethnicity of the affected along with the
      inheritance pattern and the associated epileptic phenotype. We also summarize our
      current understanding on the pathophysiology of the SCN1A gene defects, disease
      mechanism, genetic modifiers and their clinical and diagnostic relevance. 

PMID- 23884152
TI  - Binding of oxo-Cu2 clusters to ferric ion-binding protein A from Neisseria
      gonorrhoeae: a structural insight.
AB  - The ferric ion-binding protein A (FbpA), a member of transferrin superfamily, is
      a periplasmic iron transporter employed by many Gram-negative pathogens. Our
      experiments indicated copper(ii) could bind with Neisseria gonorrhoeae FbpA
      (NgFbpA), and the binding constant reached up to (8.7 +/- 0.2) * 10(8) M(-1)via
      UV-vis titration. The crystal structure of recombinant Cu-NgFbpA at 2.1 A
      revealed that the oxo-Cu2 clusters (dinuclear centres) assembled in the iron
      binding cleft and were bound to the two adjacent tyrosine residues (Y195 and
      Y196) of the protein, two Cu ions coordinated with two tyrosines, Y195 and Y196,
      respectively, which was different from the binding model of Fe ion with FbpA, in
      which Y195 and Y196 coordinated together with one Fe ion. While this was similar
      to the binding of Zr and Hf ion clusters, Y195 and Y196 coordinated with two
      metal ions and the MU-oxo-bridges linking the metal ions. Structural
      superimposition demonstrated that oxo-Cu2-NgFbpA still keeping an open
      conformation, similar to the apo-form of NgFbpA. The structure presented
      additional information towards an understanding of the function of FbpA, and
      provided a detailed binding model for FbpA protein with the possible metal ions
      in a biological system. 

PMID- 23884153
TI  - Rhodamine B derivative-functionalized upconversion nanoparticles for FRET-based
      Fe(3+)-sensing.
AB  - A novel fluorescence resonance energy transfer (FRET)-based probe, gamma
      cyclodextrin modified oleic acid-NaYF4:Yb, Ho upconversion nanoparticles
      functionalized with a rhodamine B derivative (RBD), has been achieved for Fe(3+)
      sensing in aqueous solution with high sensitivity and selectivity. 

PMID- 23884154
TI  - Multiway study of hybridization in nanoscale semiconductor labeled DNA based on
      fluorescence resonance energy transfer.
AB  - The resolution of the ternary-binary complex competition of a target sequence and
      of its two complementary probes in sandwich DNA hybridization is reported. To
      achieve this goal, Fluorescence Resonance Energy Transfer (FRET) between
      oligonucleotide-functionalized quantum dot (QD) nanoprobes (QD donor-QD acceptor)
      upon hybridization with a label free target was monitored by two-dimensional
      photoluminescence excitation spectroscopy (2D-PLE). Detection of a target
      oligonucleotide strand, using sandwiched nanoassembly in a separation-free
      format, was performed with the appearance of a new feature in the
      photoluminescence excitation (PLE) plot. From the obtained data, energy transfer
      efficiency and Forster radius (R0) were calculated. In particular, our results
      demonstrated that energy transfer by using QD donor-QD acceptor FRET pairs is
      more efficient in comparison with QD donor-organic dye acceptor pairs. Soft and
      model based analysis of 2D-PLE data was implemented by means of PARAFAC and hard
      trilinear decomposition (HTD), allowing to fit a proper model for FRET-based
      sandwich DNA hybridization systems. This study is the first successful
      application of a multiway chemometric technique to consider FRET based DNA
      hybridization in sandwiched nanoassemblies. A multi-equilibria model was properly
      fitted to the data and confirmed there is a competition between ternary and
      binary complex formation. Equilibrium constants of DNA hybridization in
      sandwiched nanoassemblies were estimated for the first time. Equilibrium
      constants illustrated that the extent of hybridization in one side on the target
      strand depends on hybridization conditions on the other side of the strand.
      Effects of guanine (G) and cytosine (C) contents of strands on the extent and
      rate of hybridization were investigated. In addition to equilibrium constants of
      binary and ternary complexes, the pure profiles of all resolved structures were
      estimated. Ultimately, the described method calculated the analytical
      concentration of probes as a measure of surface modification yield with DNA using
      nonlinear fit analysis, without using any calibration sample. 

PMID- 23884155
TI  - Group 4 metallocene catalysed full dehydrogenation of hydrazine borane.
AB  - A study of the full dehydrogenation of hydrazine borane (H2N-NH2.BH3) to give H2
      and N2 as gaseous products catalysed by a variety of group 4 metallocene alkyne
      complexes of the type CpM(L)(eta(2)-Me3SiC2SiMe3) (Cp' = substituted or
      unsubstituted eta(5)-cyclopentadienyl; M = Ti, no L; M = Zr, L = pyridine) and
      group 4 metallocene hydrides is presented. Volumetric data show that the amount
      of hydrogen released is strongly dependent on both, the metal and the
      cyclopentadienyl ligand. 

PMID- 23884156
TI  - Multiple (disseminated) follicular cysts in five dogs and one cat.

PMID- 23884157
TI  - Chemical influence on beta-relaxations and the formation of molecule-like
      metallic glasses.
AB  - Secondary (also known as Johari-Goldstein or beta-) relaxations are an intrinsic
      feature of supercooled liquids and glasses. They are important in many respects
      but the underlying mechanisms are not well understood. A long-standing puzzle is
      why some glasses show beta-relaxations as pronounced peaks, whereas others as
      unobvious excess wings. Here we demonstrate that these different behaviours are
      related to the fluctuations of chemical interactions by using prototypical
      systems of metallic glasses. A general rule is summarized: pronounced beta
      relaxations are associated with systems where all the atomic pairs have large
      similar negative values of enthalpy of mixing, whereas positive or significant
      fluctuations in enthalpy of mixing suppress beta-relaxations. The emerging
      physical picture is that strong and comparable interactions among all the
      constituting atoms maintain string-like atomic configurations for the excitations
      of beta-events and can be considered as the formation of molecule-like metallic
      glasses. 

PMID- 23884158
TI  - Ultrafast laser ablation and machining large-size structures on porcine bone.
AB  - When using ultrafast laser ablation in some orthopedic applications where precise
      cutting/drilling is required with minimal damage to collateral tissue, it is
      challenging to produce large-sized and deep holes using a tightly focused laser
      beam. The feasibility of producing deep, millimeter-size structures under
      different ablation strategies is investigated. X-ray computed microtomography was
      employed to analyze the morphology of these structures. Our results demonstrated
      the feasibility of producing holes with sizes required in clinical applications
      using concentric and helical ablation protocols.

PMID- 23884160
TI  - Local administration of lactic acid and a low dose of the free radical scavenger,
      edaravone, alleviates myocardial reperfusion injury in rats.
AB  - The effects of local myocardial administration of lactic acid and low-dose
      edaravone were investigated to determine if this combination provides benefits
      similar to mechanical postconditioning. We randomly divided 108 rats into 6
      groups: sham, reperfusion injury, postconditioning (Post), lactic acid (Lac), low
      dose edaravone (Eda), and lactic acid + low-dose edaravone (Lac+Eda). The left
      coronary arteries of the rats were occluded for 45 minutes, before the
      administration of the treatments. The rats were euthanized at different time
      points to examine the infarct size and serum markers of myocardial injury and
      apoptosis and measure the expression of signal pathway markers. We found that the
      infarct areas caused by ischemic-reperfusion injury were reduced largely by
      postconditioning and Lac+Eda injection; a similar trend was observed for serum
      markers of myocardial injury, apoptosis, and hemodynamic parameters. Compared
      with the Post group, the Lac+Eda group had similar blood pH values, levels of
      reactive oxygen species, mitochondrial absorbance, and levels of signal pathway
      marker. The Lac and Eda groups partly mimicked the protective role. These data
      suggest that local myocardial administration of lactic acid and low dose of
      edaravone initiates protective signal pathways of mechanical postconditioning and
      replicates the myocardial protection.

PMID- 23884161
TI  - Correction of deep static glabellar lines with acellular dermal matrix insertion.
AB  - The glabellar rhytid has not only dynamic but also static cause, which is usually
      achieved by injection of filler. Deep glabellar rhytides, however, are difficult
      to correct with filler. Therefore, the authors introduce a novel method of
      inserting a small strip of acellular dermal matrix (ADM) underneath the wrinkle
      line. From May 2009 to March 2012, 30 patients were treated for deep glabellar
      wrinkles with ADM augmentation by the senior author. The surgical outcomes were
      evaluated by the physician using the Lemperle scale and questionnaires filled out
      by the patients. The deep rhytides were significantly improved after the
      procedure, as evaluated by objective and subjective measurements, and their
      improvement lasted for a long period. No complications such as hematomas or
      infection were seen on postoperative follow-up. Augmentation with ADM provides a
      simple, easy, and minimally invasive option for the treatment of deep glabellar
      wrinkles. In cases of deep glabellar lines that cannot be corrected by filler
      injection, this procedure can be recommended as another option. 

PMID- 23884159
TI  - Heart failure and mitochondrial dysfunction: the role of mitochondrial
      fission/fusion abnormalities and new therapeutic strategies.
AB  - The treatment of heart failure (HF) has evolved during the past 30 years with the
      recognition of neurohormonal activation and the effectiveness of its inhibition
      in improving the quality of life and survival. Over the past 20 years, there has
      been a revolution in the investigation of the mitochondrion with the development
      of new techniques and the finding that mitochondria are connected in networks and
      undergo constant division (fission) and fusion, even in cardiac myocytes. This
      has led to new molecular and cellular discoveries in HF, which offer the
      potential for the development of new molecular-based therapies. Reactive oxygen
      species are an important cause of mitochondrial and cellular injury in HF, but
      there are other abnormalities, such as depressed mitochondrial fusion, that may
      eventually become the targets of at least episodic treatment. The overall need
      for mitochondrial fission/fusion balance may preclude sustained change in either
      fission or fusion. In this review, we will discuss the current HF therapy and its
      impact on the mitochondria. In addition, we will review some of the new drug
      targets under development. There is potential for effective, novel therapies for
      HF to arise from new molecular understanding.

PMID- 23884162
TI  - High-density lipoprotein subfractions display proatherogenic properties in
      overweight and obese children.
AB  - BACKGROUND: In adults, obesity-driven inflammation can lead to increased
      cardiovascular disease (CVD). However, information regarding childhood obesity
      and its inflammatory sequelae is less well defined. Serum amyloid-A (SAA) is an
      inflammatory molecule that rapidly associates with high-density lipoproteins
      (HDLs) and renders them dysfunctional. Therefore, SAA may be a useful biomarker
      to identify increased CVD potential in overweight and obese children. METHODS:
      Young Hearts 2000 is a cross-sectional cohort study in which 92 children who were
      obese were matched for age and sex with 92 overweight and 92 lean children.
      HDL(2) and HDL(3) (HDL(2&3)) were isolated from plasma by a three-step rapid
      ultracentrifugation procedure. SAA was measured in serum and HDL(2&3) by an
      enzyme-linked immunosorbent assay procedure, and the activities of cholesterol
      ester transfer protein (CETP) and lecithin cholesteryl acyltransferase (LCAT)
      were measured by fluorimetric assays. RESULTS: Trends across the groups indicated
      that SAA increased in serum and HDL(2&3) as BMI increased, as did HDL(2)-CETP and
      HDL(2)-LCAT activities. CONCLUSION: These results have provided evidence that
      overweight and obese children are exposed to an inflammatory milieu that impacts
      the antiatherogenic properties of HDL and that could increase CVD risk. This
      supports the concept that it is important to target childhood obesity to help
      minimize future cardiovascular events.

PMID- 23884163
TI  - Duration of breastfeeding and gender are associated with methylation of the
      LEPTIN gene in very young children.
AB  - BACKGROUND: Perinatal environmental factors have been associated with the
      metabolic programming of children and consequent disease risks in later life.
      Epigenetic modifications that lead to altered gene expression may be involved.
      Here, we study early life environmental and constitutional factors in association
      with the DNA methylation of leptin (LEP), a non-imprinted gene implicated in
      appetite regulation and fat metabolism. METHODS: We investigated maternal
      education, breastfeeding, and constitutional factors of the child at 17 mo of
      age. We measured the DNA methylation of LEP in whole blood and the concentration
      of leptin in serum. RESULTS: Duration of breastfeeding was negatively associated
      with LEP methylation. Low education (<=12 y of education) was associated with
      higher LEP methylation. Boys had higher birth weight and lower LEP methylation
      than girls. An inverse association was established between birth weight per SD
      increase (+584 g) and LEP methylation. High BMI and leptin concentration were
      associated with lower methylation of LEP. CONCLUSION: The early life environment
      and constitutional factors of the child are associated with epigenetic variations
      in LEP. Future studies must reveal whether breastfeeding and the associated
      decrease in LEP methylation is an epigenetic mechanism contributing to the
      protective effect of breastfeeding against obesity.

PMID- 23884164
TI  - Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible
      vectors for safe and efficient siRNA delivery.
AB  - This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic
      resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic
      gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into
      nanoclusters in the water phase with the help of stearic acid modified low
      molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO
      stPEI nanoclusters possess good stability, monodispersity with narrow size
      distribution and competitive T1-T2 dual-modal MR imaging properties. The
      nanocomposite system is capable of binding and delivering siRNA for knockdown of
      a gene of interest while maintaining its magnetic properties and
      biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an
      important platform for safe and efficient gene delivery with non-invasive T1-T2
      dual-modal MRI monitoring capability. 

PMID- 23884165
TI  - On-chip screening for prostate cancer: an EIS microfluidic platform for
      contemporary detection of free and total PSA.
AB  - Prostate cancer affects a large part of the western male population. The need for
      an early and accurate detection is thus a great challenge in common clinical
      practice, but the lack of specificity of the serum marker PSA (Prostate Specific
      Antigen) is a serious problem since its increased concentration can be related to
      several abnormalities. PSA, however, is found in serum in both a free and a
      complexed form with other proteins and the percentage amount of unbound PSA (the
      free-to-total PSA ratio) can be employed to distinguish prostate cancer from
      benign prostatic conditions, and also to predict the future risk of prostate
      cancer. To improve the operating characteristics of current PSA tests and to
      provide a clinical tool able to run label-free and sensitive analysis, we thus
      developed a biosensing platform based on Electrochemical Impedance Spectroscopy
      (EIS), which allows the contemporary detection of free and total PSA on a single
      biochip, enabling a quick screening for the risk of prostate cancer thanks to the
      presence of two different immobilized antibodies specific for the different
      antigens researched. 

PMID- 23884166
TI  - Why have studies of tailored anti-platelet therapy failed so far?
AB  - Published data linking clopidogrel non-responsiveness to adverse ischaemic events
      lead to the suggestion that the magnitude of platelet inhibition by clopidogrel
      can be monitored and individually adjusted. This has been tested in randomised
      clinical trials (ARCTIC, GRAVITAS and TRIGGER-PCI), but despite reducing platelet
      reactivity, a strategy of therapy adjustment based on platelet function
      monitoring did not reduce the incidence of cardiac ischaemic events. Several
      critical issues regarding the design of these trials, which might in part have
      led to negative results, are discussed in this article. 

PMID- 23884167
TI  - Thick intergluteal cleft and lower extremity plaques.

PMID- 23884169
TI  - Detrimental effects of metronidazole on the liver of freshwater common carp
      (Cyprinus carpio L.).
AB  - The widely used antibiotic metronidazole (MTZ) was investigated for its toxic
      effects on the liver of the common carp (Cyprinus carpio L.). The fish were
      exposed to 0.1, 0.5, and 2.5 mg/L MTZ in water for 30 days, and parameters that
      are indicative of liver damage and oxidative stress were measured. MTZ increased
      liver ethoxyresorufin-O-deethylase, malondialdehyde, and glutathione levels, and
      elevated the activities of superoxide dismutase, catalase, aspartate
      aminotransferase, and alanine aminotransferase. These parameters usually showed
      significant differences in the 0.5 and 2.5 mg/L MTZ groups compared to the
      control group (p < 0.05). These findings indicated that MTZ induced oxidative
      stress and caused liver damage in common carp, suggesting that measures should be
      taken to avoid contamination of surface waters with MTZ. 

PMID- 23884170
TI  - Aquatic toxicity assessment of esters towards the Daphnia magna through PCA
      ANFIS.
AB  - The widespread production of esters combined with their ability to migrate in
      different compartments, makes their environmental toxicity important. In this
      background, the multivariate image analysis-quantitative structure-toxicity
      relationship (MIA-QSTR) method coupled to principal component analysis-adaptive
      neuro-fuzzy inference systems (PCA-ANFIS) was applied to assess the toxicity of
      esters to Daphnia magna. In MIA-QSTR, pixels of chemical structures (2D images)
      stand for descriptors, and structural changes account for the variance in
      toxicities. The ANFIS procedure was capable of correlating the inputs (PCA
      scores) with the toxicities accurately. The PCA-ANFIS also was statistically
      validated for its predictive power using cross-validation, applicability domain
      and Y-scrambling evaluation procedures. The satisfactory results (R p (2) =
      0.926, Q LOO (2) = 0.887, R L25%O (2) = 0.843, RMSELOO = 0.320 and RMSEL25%O =
      0.379) suggests that the QSTR model could be proposed as an alternative method
      for aquatic toxicity assessment of esters allowing possible application in the
      European Union regulation REACH.

PMID- 23884168
TI  - Time course of SERCA 2b and calreticulin expression in Purkinje neurons of
      ethanol-fed rats with behavioral correlates.
AB  - Chronic ethanol consumption for 40 weeks in adult rats results in dilation of the
      extensive smooth endoplasmic reticulum (SER), a major component of the calcium
      homeostatic system within Purkinje neuron (PN) dendrites. AIMS: The aim of the
      present study was to determine whether chronic ethanol consumption results in
      alterations of the sarco/endoplasmic reticulum Ca(2+) ATPase pump (SERCA) on the
      SER membrane of PN dendrites. The density of calreticulin, a calcium chaperone,
      was also investigated in the PN along with balancing ability. METHODS: Ninety 8
      month-old rats were exposed to rat chow, the AIN-93 M liquid control or ethanol
      diets (30/diet) for a duration of 10, 20 or 40 weeks (30/duration). Age changes
      relative to the rat chow controls were assessed with 3-month-old control rats (n
      = 10). Balance was assessed prior to euthanasia. Quantitative immunocytochemistry
      was used to determine the density of SERCA 2b + dendrites and calreticulin + PN
      soma and nuclei. Molecular layer volumes were also determined. RESULTS: Following
      40 weeks of ethanol treatment, there were ethanol-induced decreases in SERCA 2b
      densities within the dendritic arbor and decreased balancing ability on the more
      difficult round rod balance test. There were no ethanol-induced changes in
      calreticulin densities. CONCLUSION: It can be concluded that ethanol-induced
      decreases in the SERCA pump accompany SER dilation and contribute to previously
      reported ethanol-induced dendritic regression in PN. Ethanol-induced changes in
      balance also occurred. Chronic ethanol consumption does not alter calreticulin
      expression in PN.

PMID- 23884171
TI  - The study on air pollution with nickel and vanadium in Croatia by using moss
      biomonitoring and ICP-AES.
AB  - Moss samples were collected from 121 sampling sites all over Croatia during the
      summer and autumn of 2010. They were totally digested by using microwave
      digestion system and analysed by using atomic emission spectrometry with
      inductively coupled plasma (ICP-AES). Descriptive statistics and maps of
      distribution were made. The data obtained in this study were compared with those
      from the study in 2006 and additionally with the data obtained in the similar
      studies in neighbouring countries and Norway as pristine area. The median value
      of nickel is 3.16 mg kg(-1) and the content varies from 1.04 to 14.66 mg kg(-1).
      The content of vanadium ranges between 0.23 and 37.26 mg kg(-1) with the median
      value of 2.55 mg kg(-1). High contents of these elements are found in the
      vicinity of Rijeka, Zagreb and Sisak as a result of their emission from oil
      refinery, thermal power plant and industrial processes. 

PMID- 23884172
TI  - Enantioselective synthesis of benzofurans and benzoxazines via an olefin cross
      metathesis-intramolecular oxo-Michael reaction.
AB  - Chiral phosphoric acid and Hoveyda-Grubbs II were found to catalyze an olefin
      cross-metathesis-intramolecular oxo-Michael cascade reaction of the ortho
      allylphenols and enones to provide a variety of benzofuran and benzoxazine
      derivatives in moderate to good yields and enantioselectivity. 

PMID- 23884174
TI  - Epigenomics comes of age with expanding roles in biological understanding and
      clinical application.

PMID- 23884173
TI  - A cocaine-regulated and amphetamine-regulated transcript inhibits oxidative
      stress in neurons deprived of oxygen and glucose.
AB  - Stroke, of which about 87% is ischemic stroke, constitutes one of the main causes
      of morbidity, disability, and mortality worldwide. Ischemic brain injury has
      complex pathological mechanisms. Considerable evidence has been collected over
      the last few years suggesting that oxidative stress associated with excessive
      production of reactive oxygen species is a fundamental mechanism of brain damage
      in stroke and reperfusion after stroke. Oxidative stress is an important trigger
      of neuronal apoptosis in ischemic stroke. In this current study, it was found
      that cocaine-regulated and amphetamine-regulated transcript 55-102 (CART55-102)
      inhibited oxygen-induced and glucose deprivation (OGD)-induced neurotoxicity in a
      dose-dependent manner. The peak dose of CART55-102 was 0.4 nmol/l. In addition,
      the level of intracellular reactive oxygen species was decreased in OGD-treated
      neurons in the presence of 0.4 nmol/l CART55-102. Mitochondrial membrane
      potential (DeltaPsim) and mtDNA mRNA expressions were increased in OGD-treated
      neurons in the presence of 0.4 nmol/l CART55-102. The current study suggests that
      CART55-102, by inhibiting oxidative stress, may be developed into therapeutic
      agents for ischemic stroke. 

PMID- 23884176
TI  - Natural sesquiterpenoids.
AB  - This review covers the isolation, structural determination, synthesis and
      chemical and microbiological transformations of natural sesquiterpenoids. The
      literature from January to December 2012 is reviewed, and 471 references are
      cited.

PMID- 23884178
TI  - NIR luminescence and catalysis of multifarious salen type ytterbium complexes
      modulated by anions.
AB  - A series of five N,N'-bis(2-hydroxy-3-methoxybenzylidene)-1,3-propanediamine
      (H2L) ytterbium complexes, namely, [Yb(H2L)2(CH3OH)](ClO4)3 (1),
      [Yb(H2L)(NO3)3]2.CH2Cl2 (2), [Yb(H2L)2(NO3)]2(PF6)4.4H2O.2CH2Cl2 (3),
      [Yb(H2L)(OAc)2]2(PF6)2.4CH2Cl2 (4) and [Yb3L'3(OH)2Cl(H2O)5]Cl3.4H2O (5) (HL' = 2
      hydroxy-3-methoxybenzaldehyde), have been synthesized by reactions of H2L with
      multifarious Yb(iii) salts. X-ray diffraction analysis reveals that complex 1
      shows a unique mononuclear structure constructed from two chelating H2L ligands
      in crossover mode. Complex 2 exhibits a dinuclear structure bridged by two H2L
      ligands. Complexes 3 and 4 possess two novel dinuclear structures linked by NO3(
      ) and OAc(-) anions, respectively. Complex 5 displays a trinuclear structure
      supported by three L' and two OH(-) anions. Noticeable, complex 3 can be
      transformed from 2 by introducing (NH4)(PF6). The PF6(-) counterion plays an
      essential role in steering the structural transformation. The anions dominate the
      final structures of 1-5. All complexes 1-5 exhibit NIR luminescence, which can be
      rationalized on the basis of different structural effects. Preliminary catalytic
      studies reveal that all complexes 1-5 are able to catalyze effectively a typical
      Henry reaction with good yields. 

PMID- 23884177
TI  - RNA at 92  degrees C: the non-coding transcriptome of the hyperthermophilic
      archaeon Pyrococcus abyssi.
AB  - The non-coding transcriptome of the hyperthermophilic archaeon Pyrococcus abyssi
      is investigated using the RNA-seq technology. A dedicated computational pipeline
      analyzes RNA-seq reads and prior genome annotation to identify small RNAs,
      untranslated regions of mRNAs, and cis-encoded antisense transcripts. Unlike
      other archaea, such as Sulfolobus and Halobacteriales, P. abyssi produces few
      leaderless mRNA transcripts. Antisense transcription is widespread (215
      transcripts) and targets protein-coding genes that are less conserved than
      average genes. We identify at least three novel H/ACA-like guide RNAs among the
      newly characterized non-coding RNAs. Long 5' UTRs in mRNAs of ribosomal proteins
      and amino-acid biosynthesis genes strongly suggest the presence of cis-regulatory
      leaders in these mRNAs. We selected a high-interest subset of non-coding RNAs
      based on their strong promoters, high GC-content, phylogenetic conservation, or
      abundance. Some of the novel small RNAs and long 5' UTRs display high GC
      contents, suggesting unknown structural RNA functions. However, we were surprised
      to observe that most of the high-interest RNAs are AU-rich, which suggests an
      absence of stable secondary structure in the high-temperature environment of P.
      abyssi. Yet, these transcripts display other hallmarks of functionality, such as
      high expression or high conservation, which leads us to consider possible RNA
      functions that do not require extensive secondary structure. 

PMID- 23884179
TI  - Accelerating water transport through a charged SWCNT: a molecular dynamics
      simulation.
AB  - The properties of a nanotube, such as the hydrophobicity and charge of the
      surface, can significantly affect water transport behavior. However, our
      knowledge of the effects of charge density, dipole orientation, frequency of
      flipping, and movement behavior on water flow through carbon nanotubes (CNTs) is
      far from adequate. This study is aimed at gaining insight into the transport of
      single-file water molecules in a charged carbon nanotube. It was shown that the
      water chains inside the charged nanotube exhibit bipolar properties. The water
      dipoles are parallel to the z-axis, and point toward (D-defect) and away from (L
      defect) the center of the nanotube for a negatively charged nanotube and a
      positively charged one, respectively. Compared with a pristine single-wall carbon
      nanotube (SWCNT), the charged nanotubes, including both positively charged and
      negatively charged, favor the water-filling process due to electrostatic
      interactions. According to the dipole distribution in the nanotube, the water
      dipole only flips in the middle region because of the bipolar nature of water
      chains. Additionally, flipping of the entire water chain is inhibited, which
      allows for the enhanced water flux. A negatively charged single-walled carbon
      nanotube (N-SWCNT) accelerated water transport by tuning the single-file flow
      from a "hopping" to a "continuous" mode, thus decreasing the energy barrier. The
      hydrogen bonds between water molecules inside the nanotube are also strengthened
      in the negatively charged nanotube, favoring water transport. Any distortion of
      uniformity will lead to additional energy barriers to water flux. Our results
      provide a comprehensive view of molecular events underpinning the water transport
      inside a SWCNT, which may be of assistance in creating innovative designs for
      water nanochannels. 

PMID- 23884180
TI  - Changes in the regulation of cortical neurogenesis contribute to encephalization
      during amniote brain evolution.
AB  - The emergence of larger brains with large numbers of neurons is an evolutionary
      innovation in mammals and birds. However, the corresponding changes in cortical
      developmental programmes during amniote evolution are poorly understood. Here we
      examine the cortical development of Madagascar ground geckos, and report unique
      characteristics of their reptilian cortical progenitors. The rates of
      proliferation and neuronal differentiation in the gecko cortex are much lower
      than those in other amniotes. Notch signalling is highly activated in the gecko
      cortical progenitors, which provides a molecular basis for the low rate of
      cortical neurogenesis. Interestingly, multiple neuron subtypes are sequentially
      generated in the gecko cortex, similar to other amniotes. These results suggest
      that changes in the regulation of cortical neural progenitors have accelerated
      neurogenesis and provided encephalization in mammalian and archosaurian lineages.
      In addition, the temporal regulation for making cortical neuronal subtypes has
      evolved in a common ancestor(s) of amniotes. 

PMID- 23884182
TI  - Erythropoiesis-stimulating agents in heart failure: no proof of effectiveness or
      proof of no effectiveness?

PMID- 23884181
TI  - Purification of monoclonal antibodies by hydrophobic interaction chromatography
      under no-salt conditions.
AB  - Hydrophobic interaction chromatography (HIC) is commonly used as a polishing step
      in monoclonal antibody purification processes. HIC offers an orthogonal
      selectivity to ion exchange chromatography and can be an effective step for
      aggregate clearance and host cell protein reduction. HIC, however, suffers from
      the limitation of use of high concentrations of kosmotropic salts to achieve the
      desired separation. These salts often pose a disposal concern in manufacturing
      facilities and at times can cause precipitation of the product. Here, we report
      an unconventional way of operating HIC in the flowthrough (FT) mode with no
      kosmotropic salt in the mobile phase. A very hydrophobic resin is selected as the
      stationary phase and the pH of the mobile phase is modulated to achieve the
      required selectivity. Under the pH conditions tested (pH 6.0 and below),
      antibodies typically become positively charged, which has an effect on its
      polarity and overall surface hydrophobicity. Optimum pH conditions were chosen
      under which the antibody product of interest flowed through while impurities such
      as aggregates and host cell proteins bound to the column. This strategy was
      tested with a panel of antibodies with varying pI and surface hydrophobicity.
      Performance was comparable to that observed using conventional HIC conditions
      with high salt. 

PMID- 23884183
TI  - Fluid drag reduction and efficient self-cleaning with rice leaf and butterfly
      wing bioinspired surfaces.
AB  - Researchers are continually inspired by living nature to solve complex
      challenges. For example, unique surface characteristics of rice leaves and
      butterfly wings combine the shark skin (anisotropic flow leading to low drag) and
      lotus leaf (superhydrophobic and self-cleaning) effects, producing the so-called
      rice and butterfly wing effect. In this paper, we present an overview of rice
      leaf and butterfly wing fluid drag and self-cleaning studies. In addition, we
      examine two other promising aquatic surfaces in nature known for such properties,
      including fish scales and shark skin. Morphology, drag, self-cleaning, contact
      angle, and contact angle hysteresis data are presented to understand the role of
      wettability, viscosity, and velocity. Liquid repellent coatings are utilized to
      recreate or combine various effects. Discussion is provided along with conceptual
      models describing the role of surface structures related to low drag, self
      cleaning, and antifouling properties. Modeling provides design guidance when
      developing novel low drag and self-cleaning surfaces for applications in the
      medical, marine, and industrial fields. 

PMID- 23884184
TI  - Hepatitis B vaccination and undifferentiated connective tissue disease: another
      brick in the wall of the autoimmune/inflammatory syndrome induced by adjuvants
      (Asia).

PMID- 23884185
TI  - Pregnancy in rheumatic disease patients.

PMID- 23884186
TI  - Hydroxychloroquine-induced hyperpigmentation.

PMID- 23884187
TI  - An unusual case of forearm swelling.

PMID- 23884188
TI  - Bone marrow edema in the sacroiliac joint due to sacral stress fracture.

PMID- 23884190
TI  - New therapies, increased risk for old infections--abdominal tuberculosis
      mimicking colon cancer during adalimumab treatment for rheumatoid arthritis.

PMID- 23884191
TI  - Comment on diffuse alveolar hemorrhage and Libman-Sacks endocarditis as a
      manifestation of possible primary antiphospholipid syndrome.

PMID- 23884192
TI  - Author's response.

PMID- 23884193
TI  - Facile synthesis of low crystalline MoS2 nanosheet-coated CNTs for enhanced
      hydrogen evolution reaction.
AB  - In this work, a networked MoS2/CNT nanocomposite has been synthesized by a facile
      solvothermal method. The as-prepared sample exhibits high catalytic activity for
      electrocatalytic hydrogen evolution. 

PMID- 23884194
TI  - Ectopic fat: the true culprit linking obesity and cardiovascular disease?
AB  - Obesity is a major risk factor for cardiovascular disease and its complications.
      However, not all fat depots share the same characteristics. Recent studies have
      found that ectopic rather than subcutaneous fat accumulation is associated with
      increased cardiometabolic risk. However, ectopic fat accumulation can be seen
      initially as a protective mechanism against lipotoxicity. Subsequently the
      adipose tissue becomes dysfunctional, thus inducing systemic metabolic
      alterations (through release of cytokines) or specific organ dysfunctions. The
      purpose of this review is to summarise the current available data on the impact
      of excess adiposity vs ectopic fat in the development of cardio-metabolic
      diseases. 

PMID- 23884195
TI  - Diffuse ventricular fibrosis is a late outcome of tachycardia-mediated
      cardiomyopathy after successful ablation.
AB  - BACKGROUND: Successful arrhythmia ablation normalizes ejection fraction (EF) in
      tachycardia-mediated cardiomyopathy, but recurrent heart failure and late sudden
      death have been reported. The aim of this study was to characterize the left
      ventricle (LV) of tachycardia-mediated cardiomyopathy patients long after
      definitive arrhythmia cure. METHODS AND RESULTS: Thirty-three patients with a
      history of successfully ablated incessant focal atrial tachycardia 64+/-36 months
      prior, and 20 healthy controls were recruited. At ablation, 18 patients had
      EF<50% (AT-low EF) that recovered within 3 months from 37+/-12 to 56+/-4%
      (P<0.001), whereas 15 patients had EF>55% (AT-normal EF). No subjects had EF of
      50% to 55%. Subjects underwent echocardiography with speckle tracking and
      contrast-enhanced cardiac MRI with ventricular T1 mapping as an index of diffuse
      fibrosis. Contrast-enhanced cardiac MRI was performed using a clinical 1.5-T
      scanner and 0.2 mmol/kg gadolinium-diethylene triamine penta-acetic acid for
      contrast. Subject characteristics were similar across the 3 groups. Compared with
      AT-normal EF patients and controls, AT-low EF patients had lower EF (60+/-6
      versus 64+/-4 and 65+/-4%; P<0.05), greater indexed LV end-diastolic volume
      (102+/-34 versus 84+/-14 and 85+/-16 mL/m(2); P<0.05), and greater indexed LV end
      systolic volume (41+/-11 versus 31+/-7 and 30+/-8 mL/m(2); P<0.01) on contrast
      enhanced cardiac MRI. Compared with controls, AT-low EF patients had reduced
      global LV corrected T1 time (442+/-53 versus 529+/-61; P<0.05) consistent with
      diffuse fibrosis. CONCLUSIONS: Tachycardia-mediated cardiomyopathy patients
      exhibit differences in LV structure and function including diffuse fibrosis long
      after arrhythmia cure, indicating that recovery is incomplete.

PMID- 23884196
TI  - A novel method for determining the phase of T-wave alternans: diagnostic and
      therapeutic implications.
AB  - BACKGROUND: T-wave alternans (TWA) has been implicated in the pathogenesis of
      ventricular arrhythmias and sudden cardiac death. However, to estimate and
      suppress TWA effectively, the phase of TWA must be accurately determined. METHODS
      AND RESULTS: We developed a method that computes the beat-by-beat integral of the
      T-wave morphology, over time points within the T-wave with positive alternans.
      Then, we estimated the signed derivative of the T-wave integral sequence, which
      allows the classification of each beat to a binary phase index. In animal
      studies, we found that this method was able to accurately identify the T-wave
      phase in artificially induced alternans (P<0.0001). The coherence of the phase
      increased consistently after acute ischemia induction in all body-surface and
      intracardiac leads (P<0.0001). Also, we developed a phase-resetting detection
      algorithm that enhances the diagnostic utility of TWA. We further established an
      algorithm that uses the phase of TWA to deliver appropriate polarity-pacing
      pulses (all interventions compared with baseline, P<0.0001 for alternans voltage;
      P<0.0001 for K(score)), to suppress TWA. Finally, we demonstrated that using the
      phase of TWA we can suppress spontaneous TWA during acute ischemia; 77.6% for
      alternans voltage (P<0.0001) and 92.5% for K(score) (P<0.0001). CONCLUSIONS: We
      developed a method to quantify the temporal variability of the TWA phase. This
      method is expected to enhance the utility of TWA in predicting ventricular
      arrhythmias and sudden cardiac death and raises the possibility of using upstream
      therapies to abort a ventricular tachyarrhythmia before its onset.

PMID- 23884197
TI  - Nicotinamide adenine dinucleotide phosphate oxidase 4 mediates the differential
      responsiveness of atrial versus ventricular fibroblasts to transforming growth
      factor-beta.
AB  - BACKGROUND: Atrial fibrosis, a common feature of atrial fibrillation, is thought
      to originate from the differential response of atrium versus ventricle to
      pathological insult. However, detailed mechanisms underlying the regional
      differences remain unclear. The aim of this study was to investigate the related
      factor(s) in mediating atrial vulnerability to fibrotic processes. METHODS AND
      RESULTS: We first compared the response of cultured atrial versus ventricular
      fibroblasts with transforming growth factor-beta (TGF-beta), a key mediator of
      myocardial fibrosis. Atrial fibroblasts showed a stronger response to TGF-beta1
      in producing extracellular matrix protein (collagen and fibronectin) than
      ventricular fibroblasts. Furthermore, TGF-beta1 activated its downstream
      signaling (Smads) and induced pronounced oxidative stress, including up
      regulation of nicotinamide adenine dinucleotide phosphate oxidase in atrial
      fibroblasts, and to a lesser extent in ventricular fibroblasts. Nicotinamide
      adenine dinucleotide phosphate oxidase inhibitors and small-interfering RNA for
      Nox4 eliminated TGF-beta-induced difference between atrial and ventricular
      fibroblasts, suggesting the crucial role of Nox4 in mediating the atrial
      ventricular discrepancy. Small-interfering RNA for Smad3 also suppressed the
      differential responsiveness of atrial versus ventricular fibroblasts to TGF
      beta1, including Nox4 activation, implicating a crosstalk between nicotinamide
      adenine dinucleotide phosphate oxidases and Smad. In vivo, the increased TGF
      beta1 responsiveness and Nox4 expression were documented in the atria of
      transgenic mice with cardiac overexpression of TGF-beta1. CONCLUSIONS: Atrial
      fibroblasts show greater fibrotic and oxidative responses to TGF-beta1 than
      ventricular fibroblasts. Nox4-derived reactive oxygen species production mediates
      the susceptibility of atrial fibroblasts to TGF-beta1 via activating TGF
      beta1/Smad signaling cascade, which provides a novel insight into the
      pathogenesis of atrial fibrosis.

PMID- 23884198
TI  - T-type calcium current contributes to escape automaticity and governs the
      occurrence of lethal arrhythmias after atrioventricular block in mice.
AB  - BACKGROUND: When complete atrioventricular block (AVB) occurs, infranodal escape
      rhythms are essential to prevent bradycardic death. The role of T-type Ca(2+)
      channels in pacemaking outside the sinus node is unknown. We investigated the
      role of T-type Ca(2+) channels in escape rhythms and bradycardia-related
      ventricular tachyarrhythmias after AVB in mice. METHODS AND RESULTS: Adult male
      mice lacking the main T-type Ca(2+) channel subunit Cav3.1 (Cav3.1(-/-)) and wild
      type (WT) controls implanted with ECG telemetry devices underwent radiofrequency
      atrioventricular node ablation to produce AVB. Before ablation, Cav3.1(-/-) mice
      showed sinus bradycardia (mean+/-SEM; RR intervals, 148+/-3 versus 128+/-2 ms WT;
      P<0.001). Immediately after AVB, Cav3.1(-/-) mice had slower escape rhythms (RR
      intervals, 650+/-75 versus 402+/-26 ms in WT; P<0.01) but a preserved heart-rate
      response to isoproterenol. Over the next 24 hours, mortality was markedly greater
      in Cav3.1(-/-) mice (19/31; 61%) versus WT (8/26; 31%; P<0.05), and Torsades de
      Pointes occurred more frequently (73% Cav3.1(-/-) versus 35% WT; P<0.05). Escape
      rhythms improved in both groups during the next 4 weeks but remained
      significantly slower in Cav3.1(-/-). At 4 weeks after AVB, ventricular
      tachycardia was more frequent in Cav3.1(-/-) than in WT mice (746+/-116 versus
      214+/-78 episodes/24 hours; P<0.01). Ventricular function remodeling was similar
      in Cav3.1(-/-) and WT, except for smaller post-AVB fractional-shortening increase
      in Cav3.1(-/-). Expression changes were seen post-AVB for a variety of genes;
      these tended to be greater in Cav3.1(-/-) mice, and overexpression of fetal and
      profibrotic genes occurred only in Cav3.1(-/-). CONCLUSIONS: This study suggests
      that T-type Ca(2+) channels play an important role in infranodal escape
      automaticity. Loss of T-type Ca(2+) channels worsens bradycardia-related
      mortality, increases bradycardia-associated adverse remodeling, and enhances the
      risk of malignant ventricular tachyarrhythmias complicating AVB.

PMID- 23884199
TI  - Characterization of anatomic ventricular tachycardia isthmus pathology after
      surgical repair of tetralogy of Fallot.
AB  - BACKGROUND: Although catheter ablation has been used to target the critical
      isthmuses for re-entrant monomorphic ventricular tachycardia in tetralogy of
      Fallot, the anatomy and histology of these regions have not been fully
      characterized. Autopsy hearts with tetralogy of Fallot were evaluated to clarify
      the pathological substrate. METHODS AND RESULTS: Twenty-seven hearts with the
      diagnosis of tetralogy of Fallot were examined. Anatomically defined isthmuses
      included (1A) ventriculotomy-to-tricuspid annulus, (1B) ventriculotomy-to
      ventricular septal defect patch, (2) ventriculotomy-to-pulmonary annulus, (3)
      pulmonary annulus-to-ventricular septal defect patch, and (4) ventricular septal
      defect patch-to-tricuspid annulus. Length and wall thickness were measured for
      all specimens, and light microscopy was performed for those surviving surgery.
      For subjects>=5 years at death, isthmuses 1A and 1B were present in 88%, isthmus
      2 in 25%, isthmus 3 in 94%, and isthmus 4 in 13%. Isthmus 1A had the greatest
      dimensions (mean length, 3.9+/-1.08; thickness, 1.5+/-0.3 cm), isthmus 1B
      intermediate dimensions (mean length, 2.4+/-0.8; thickness, 1.1+/-0.4 cm), and
      isthmuses 2, 3, and 4 the smallest dimensions (mean length, 1.5+/-0.5, 1.4+/-0.8,
      and 0.6+/-0.4 cm; thickness, 0.5+/-0.2, 0.6+/-0.2, and 0.3+/-0.04 cm,
      respectively). Histological examination (n=7) revealed increased fibrosis in
      anatomic isthmuses relative to nonisthmus controls. CONCLUSIONS: Consistencies in
      isthmus dimensions and histology are found among patients with repaired tetralogy
      of Fallot. Isthmus 1A is associated with the largest morphological dimensions,
      whereas the nearby newly described isthmus 1B is significantly smaller. Of
      isthmuses with the smallest dimensions, isthmus 3 is the most common.

PMID- 23884200
TI  - One-pot squaric acid diester mediated aqueous protein conjugation.
AB  - A water-soluble squaric acid dialkyl diester derivative is presented, which
      enables one-pot, two-step amine-selective protein conjugation reactions with
      (functional) amines in water. This reagent not only allows all-aqueous protein
      modifications, but also tolerates e.g. hydroxyl groups and can also be used for
      the modification of proteins with water-insoluble amines. 

PMID- 23884201
TI  - Automatic characterization of neointimal tissue by intravascular optical
      coherence tomography.
AB  - Intravascular optical coherence tomography (IVOCT) is rapidly becoming the method
      of choice for assessing vessel healing after stent implantation due to its unique
      axial resolution <20  MUm. The amount of neointimal coverage is an important
      parameter. In addition, the characterization of neointimal tissue maturity is
      also of importance for an accurate analysis, especially in the case of drug
      eluting and bioresorbable stent devices. Previous studies indicated that well
      organized mature neointimal tissue appears as a high-intensity, smooth, and
      homogeneous region in IVOCT images, while lower-intensity signal areas might
      correspond to immature tissue mainly composed of acellular material. A new method
      for automatic neointimal tissue characterization, based on statistical texture
      analysis and a supervised classification technique, is presented. Algorithm
      training and validation were obtained through the use of 53 IVOCT images
      supported by histology data from atherosclerotic New Zealand White rabbits. A
      pixel-wise classification accuracy of 87% and a two-dimensional region-based
      analysis accuracy of 92% (with sensitivity and specificity of 91% and 93%,
      respectively) were found, suggesting that a reliable automatic characterization
      of neointimal tissue was achieved. This may potentially expand the clinical value
      of IVOCT in assessing the completeness of stent healing and speed up the current
      analysis methodologies (which are, due to their time- and energy-consuming
      character, not suitable for application in large clinical trials and clinical
      practice), potentially allowing for a wider use of IVOCT technology.

PMID- 23884202
TI  - German-Catalan workshop on epigenetics and cancer.
AB  - In the First German-Catalan Workshop on Epigenetics and Cancer held in
      Heidelberg, Germany (June 17-19, 2013), cutting-edge laboratories (PEBC, IMPPC,
      DKFZ, and the Collaborative Research Centre Medical Epigenetics of Freiburg)
      discussed the latest breakthroughs in the field. The importance of DNA
      demethylation, non-coding and imprinted genes, metabolic stress, and cell
      transdifferentiation processes in cancer and non-cancer diseases were addressed
      in several lectures in a very participative and dynamic atmosphere.   The meeting
      brought together leading figures in the field of cancer epigenetics to present
      their research work from the last five years. Experts in different areas of
      oncology described important advances in colorectal, lung, neuroblastoma,
      leukemia, and lymphoma cancers. The workshop also provided an interesting forum
      for pediatrics, and focused on the need to improve the treatment of childhood
      tumors in order to avoid, as far as possible, brain damage and disruption of
      activity in areas of high plasticity. From the beginning, the relevance of
      "omics" and the advances in genome-wide analysis platforms, which allow cancer to
      be studied in a more comprehensive and inclusive way, was very clear. Modern
      "omics" offer the possibility of identifying metastases of uncertain origin and
      establishing epigenetic signatures linked to a specific cluster of patients with
      a particular prognosis. In this context, invited speakers described novel tumor
      associated histone variants and DNA-specific methylation, highlighting their
      close connection with other processes such as cell-lineage commitment and
      stemness. 

PMID- 23884203
TI  - Maltose-forming alpha-amylase from the hyperthermophilic archaeon Pyrococcus sp.
      ST04.
AB  - The deduced amino acid sequence from a gene of the hyperthermophilic archaeon
      Pyrococcus sp. ST04 (Py04_0872) contained a conserved glycoside hydrolase family
      57 (GH57) motif, but showed <13% sequence identity with other known Pyrococcus
      GH57 enzymes, such as 4-alpha-glucanotransferase (EC 2.4.1.25), amylopullulanase
      (EC 3.2.1.41), and branching enzyme (EC 2.4.1.18). This gene was cloned and
      expressed in Escherichia coli, and the recombinant product (Pyrococcus sp. ST04
      maltose-forming alpha-amylase, PSMA) was a novel 70-kDa maltose-forming alpha
      amylase. PSMA only recognized maltose (G2) units with alpha-1,4 and alpha-1,6
      linkages in polysaccharides (e.g., starch, amylopectin, and glycogen) and
      hydrolyzed pullulan very poorly. G2 was the primary end product of hydrolysis.
      Branched cyclodextrin (CD) was only hydrolyzed along its branched
      maltooligosaccharides. 6-O-glucosyl-beta-cyclodextrin (G1-beta-CD) and beta
      cyclodextrin (beta-CD) were resistant to PSMA suggesting that PSMA is an exo-type
      glucan hydrolase with alpha-1,4- and alpha-1,6-glucan hydrolytic activities. The
      half-saturation value (Km) for the alpha-1,4 linkage of maltotriose (G3) was 8.4
      mM while that of the alpha-1,6 linkage of 6-O-maltosyl-beta-cyclodextrin (G2-beta
      CD) was 0.3 mM. The kcat values were 381.0 min(-1) for G3 and 1,545.0 min(-1) for
      G2-beta-CD. The enzyme was inhibited competitively by the reaction product G2,
      and the Ki constant was 0.7 mM. PSMA bridges the gap between amylases that
      hydrolyze larger maltodextrins and alpha-glucosidase that feeds G2 into
      glycolysis by hydrolyzing smaller glucans into G2 units.

PMID- 23884204
TI  - Growth, lipid production and metabolic adjustments in the euryhaline
      eustigmatophyte Nannochloropsis oceanica CCALA 804 in response to osmotic
      downshift.
AB  - We investigated the effects of osmotic downshift induced by the transfer of
      Nannochloropsis oceanica CCALA 804 from artificial seawater medium (27 g L(-1)
      NaCl) to the same medium without NaCl or freshwater modified BG-11 medium (mBG
      11) as a function of photosynthetically active radiation (170, 350, or 700 MUmol
      photon m(-2) s(-1)). Alterations in growth, total fatty acid (FA) content and FA
      composition of individual lipid classes, and in relative contents of metabolites
      relevant to osmotic adjustments were studied. Cells displayed remarkable
      tolerance to the osmotic downshift apart from some swelling, with no substantial
      lag or decline in cell division rate. Biomass accumulation and chlorophyll a
      content were enhanced upon downshifting, especially under the highest irradiance.
      The highest chlorophyll a and eicosapentaenoic acid (EPA) biomass and culture
      contents were determined in the cultures grown in mBG-11. Two days after transfer
      to 0 g L(-1) NaCl, the proportion in total acyl lipids of the major chloroplast
      galactolipid monogalactosyldiacylglycerol, a major depot of EPA, increased
      twofold, along with a modest change in the proportion of
      digalactosyldiacylglycerol (DGDG). EPA percentage decreased in DGDG and increased
      in the extraplastidial lipid phosphatidylethanolamine. Metabolite profiling by GC
      MS analysis revealed a sharp decrease in metabolites potentially involved in
      osmoregulation, such as mannitol and proline, while proline-cycle intermediates
      and some free sugars increased. The stress-induced polyamine spermidine decreased
      ca. one order of magnitude, while its catabolic product-the non-protein amino
      acid gamma-amino butyric acid-increased twofold, as did the stress-related sugars
      trehalose and talose. Biochemical mechanisms governing osmotic plasticity and
      implications for optimization of EPA production by N. oceanica CCALA 804 under
      variable cultivation conditions are discussed. 

PMID- 23884205
TI  - Cloning and heterologous expression of plnE, -F, -J and -K genes derived from
      soil metagenome and purification of active plantaricin peptides.
AB  - Plantaricin gene-specific primers were used to obtain plnE, -F, -J and -K
      structural gene amplicons from soil metagenome. These amplicons were cloned and
      expressed in pET32a (+) vector in Escherichia coli BL21 (DE3). PlnE, -F, -J and 
      K peptides were expressed as His-tagged-fusion proteins and were separated by
      Ni(2+) -chelating affinity chromatography. The peptides were released from the
      fusion by enterokinase cleavage and separated from the carrier thioredoxin. The
      cleaved peptides were further analysed for antimicrobial activity and found to be
      active against Listeria innocua NRRL B33314, Micrococcus luteus MTCC 106 and
      lactic acid bacteria, such as Enterococcus casseliflavus NRRL B3502, Lactococcus
      lactis lactis NRRL 1821, Lactobacillus curvatus NRRL B4562 and Lactobacillus
      plantarum NRRL B4496. E. coli has been successfully exploited as a host for
      heterologous expression with a significant yield of fused and cleaved peptides in
      the range of 8-12 and 1-1.5 mg/l of the culture, respectively. Heterologous
      expression, therefore, can be used to overcome the constraints of low yield often
      reported from a native strain.

PMID- 23884206
TI  - Clinical Trial Simulation to Inform Phase 2: Comparison of Concentrated vs.
      Distributed First-in-Patient Study Designs in Psoriasis.
AB  - Clinical trial simulation (CTS) and model-based meta-analysis (MBMA) can increase
      our understanding of small, first-in-patient (FIP) trial design performance to
      inform Phase 2 decision making. In this work, we compared dose-ranging designs
      vs. designs testing only placebo and the maximum dose for early decision making
      in psoriasis. Based on MBMA of monoclonal antibodies in the psoriasis space, a
      threshold of greater than a 50 percentage point improvement over placebo effect
      at the highest feasible drug dose was required for the advancement in psoriasis.
      Studies testing only placebo and the maximum dose made the correct advancement
      decision marginally more often than dose-ranging designs in the majority of the
      cases. However, dose-ranging studies in FIP trials offer important design
      advantages in the form of dose-response (D-R) information to inform Phase 2 dose
      selection. CTS can increase the efficiency and quality of drug development
      decision making by studying the limitations and benefits of study designs
      prospectively.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e58;
      doi:10.1038/psp.2013.32; published online 24 July 2013. 

PMID- 23884207
TI  - Development of a Physiologically-Based Pharmacokinetic Model for Sirolimus:
      Predicting Bioavailability Based on Intestinal CYP3A Content.
AB  - Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) and is
      increasingly being used in transplantation and cancer therapies. Sirolimus has
      low oral bioavailability and exhibits large pharmacokinetic variability. The
      underlying mechanisms for this variability have not been explored to a large
      extent. Sirolimus metabolism was characterized by in vitro intrinsic clearance
      estimation. Pathway contribution ranked from CYP3A4 > CYP3A5 > CYP2C8. With the
      well stirred and Qgut models sirolimus bioavailability was predicted at 15%.
      Interindividual differences in bioavailability could be attributed to variable
      intestinal CYP3A expression. The physiologically-based pharmacokinetics (PBPK)
      model developed in Simcyp predicted a high distribution of sirolimus into adipose
      tissue and another elimination pathway in addition to CYP-mediated metabolism.
      PBPK model predictive performance was acceptable with Cmax and area under the
      curve (AUC) estimates within 20% of observed data in a dose escalation study. The
      model also showed potential to assess the impact of hepatic impairment and drug
      drug interaction (DDI) on sirolimus pharmacokinetics.CPT: Pharmacometrics &
      Systems Pharmacology (2013) 2, e59; doi:10.1038/psp.2013.33; published online 24
      July 2013. 

PMID- 23884208
TI  - Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens
      Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta
      analysis.
AB  - IMPORTANCE: The US Food and Drug Administration recommends screening for the HLA
      B*1502 allele before initiation of carbamazepine therapy in patients of Asian
      ancestry, but there remains unclear evidence of a relationship between HLA-B*1502
      and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among
      carbamazepine users, especially in some racial/ethnic populations. OBJECTIVE: To
      determine the relationship between the HLA-B*1502 allele and carbamazepine
      induced SJS and TEN. DATA SOURCES: A comprehensive search of the following data
      sources was performed without language restriction from the inception of the
      database until January 8, 2013: EMBASE, PubMed, clinicaltrials.gov, Cochrane
      Library, IPA (International Pharmaceutical Abstracts), HuGENet (Human Genome
      Epidemiology Network), and CINAHL (Cumulative Index to Nursing and Allied Health
      Literature), and the reference lists of identified studies. STUDY SELECTION:
      Inclusion criteria were studies that investigated the relationship between HLA
      B*1502 and carbamazepine-induced SJS and TEN and that reported sufficient data
      for calculating the frequency of HLA-B*1502 carriers among cases and controls.
      The search yielded 525 articles, of which 16 met the inclusion criteria. The
      studies included 227 SJS or TEN cases, 602 matched control subjects, and 2949
      population control subjects. DATA EXTRACTION AND SYNTHESIS: Two reviewers
      independently extracted the following data: study design, eligibility criteria,
      diagnostic criteria, patient demographics, genotype distribution, HLA-B
      genotyping technique, selection of cases and controls, dosage of carbamazepine
      and duration of use, and results of Hardy-Weinberg equilibrium in the control
      group. The Newcastle-Ottawa Scale was used to assess the quality of studies. The
      overall odds ratios (ORs) with corresponding 95% CIs were calculated using a
      random-effects model. The primary analysis was based on matched control studies.
      Subgroup analyses by race/ethnicity were also performed. MAIN OUTCOME AND
      MEASURE: The primary outcome was carbamazepine-induced SJS and TEN. The outcome
      measure is given as an overall OR. RESULTS: The summary OR for the relationship
      between HLA-B*1502 and carbamazepine-induced SJS and TEN was 79.84 (95% CI, 28.45
      224.06). Racial/ethnic subgroup analyses yielded similar findings for Han-Chinese
      (115.32; 18.17-732.13), Thais (54.43; 16.28-181.96), and Malaysians (221.00; 3.85
      12 694.65). Among individuals of white or Japanese race/ethnicity, no patients
      with SJS or TEN were carriers of the HLA-B*1502 allele. CONCLUSIONS AND
      RELEVANCE: We found a strong relationship between the HLA-B*1502 allele and
      carbamazepine-induced SJS and TEN in Han-Chinese, Thai, and Malaysian
      populations. HLA-B*1502 screening in patients requiring carbamazepine therapy is
      warranted.

PMID- 23884209
TI  - Genomagnetic assay for electrochemical detection of osteogenic differentiation in
      mesenchymal stem cells.
AB  - The osteogenic differentiation of mesenchymal stem cells (MSCs) was assessed by
      determining the gene expression levels of proteins; osteocalcin (OSC),
      osteonectin (OSN) and osteopontin (OSP) based on electrochemical detection
      protocol combined with genomagnetic assay in parallel to real-time PCR analysis.
      Genomagnetic assay was performed using streptavidin coated commercial magnetic
      particles (magnetic beads, MBs) in combination with single-use electrochemical
      sensor technology. A biotinylated DNA probe was immobilized onto streptavidin
      coated magnetic particles, and then the hybridization process of the probe with
      its complementary DNA was performed. The oxidation signals of DNA electroactive
      bases guanine and adenine were measured voltammetrically using a pencil graphite
      electrode (PGE) before and after the hybridization process of OSC/OSN/OSP probe
      sequences with their complementary target sequences. The selectivity of the
      genomagnetic assay was also tested using each DNA probe individually related to
      osteogenic differentiations. The voltammetric detection of osteogenic
      differentiations was confirmed selectively by real-time PCR analysis. 

PMID- 23884210
TI  - C-Cl activation of the weakly coordinating anion [B(3,5-Cl2C6H3)4]- at a Rh(I)
      centre in solution and the solid-state.
AB  - Addition of H2 to [Rh((i)Bu2PCH2CH2P(i)Bu2)(NBD)][BAr(Cl)4] (NBD = norbornadiene,
      Ar(Cl) = 3,5-Cl2C6H3) in the solid-state results in the rapid formation of
      zwitterionic [Rh((i)Bu2PCH2CH2P(i)Bu2){(eta(6)-C6H3Cl2)BAr(Cl)3}] by a gas/solid
      reaction. This undergoes slow C-Cl bond cleavage in the solid-state to ultimately
      afford the dimeric Rh(III) complex
      [RhCl((i)Bu2PCH2CH2P(i)Bu2){C6H3Cl(BAr(Cl)3)}]2. This reactivity is mirrored in
      solution (CH2Cl2). Kinetic data for the C-Cl activation in both the solid-state
      and solution are reported.

PMID- 23884212
TI  - Size-dependent oxygen storage ability of nano-sized ceria.
AB  - We thermodynamically studied the size-dependent oxygen storage ability of nano
      sized ceria by tracing the surface Ce/O ratio of octahedral particles with
      different diameters, from the viewpoint of lattice Ce and O in a CeO2
      crystallographic structure. The high surface Ce/O ratio with small scale particle
      size has more excess surface Ce(4+) ions, which allows ceria to have an
      increasing oxygen storage ability in a crystalline lattice. For the perfect
      octahedron growth shape of ceria, the nonstoichiometric surfaces can produce
      excess Ce(4+) ions, Ce(4+) ions can be stabilized by bonding with lattice oxygen,
      leading to an enhanced oxygen storage ability of ceria. With the increasing
      particle size, the surface Ce/O ratio approaches to 0.5 owing to the decreased
      contributions of atoms located at the edges and corners. When the octahedron
      diameter D = 0.55 nm, the surface Ce/O ratio can reach 0.75. When D = 7.58 nm,
      the surface Ce/O ratio decreases down to 0.51. If D>= 14.61 nm, the surface Ce/O
      ratios are equal to 0.5. The present study deepens the insight of the size
      dependent oxygen storage ability of nano-sized ceria, focusing on the size
      dependent excess Ce(4+) on nonstoichiometric surfaces of ceria in thermodynamics.

PMID- 23884211
TI  - Alterations in vascular function in primary aldosteronism: a cardiovascular
      magnetic resonance imaging study.
AB  - Excess aldosterone is associated with increased cardiovascular risk. Aldosterone
      has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance
      imaging (CMR) allows study of vascular function by measuring aortic
      distensibility. We compared aortic distensibility in primary aldosteronism (PA),
      essential hypertension (EH) and normal controls and explored the relationship
      between aortic distensibility and pulse wave velocity (PWV). We studied PA (n=14)
      and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR,
      including measurement of aortic distensibility, and measured PWV using
      applanation tonometry. At recruitment, PA and EH patients had similar blood
      pressure and left ventricular mass. Subjects with PA had significantly lower
      aortic distensibility and higher PWV compared with EH and healthy controls. These
      changes were independent of other factors associated with reduced aortic
      distensibility, including ageing. There was a significant relationship between
      increasing aortic stiffness and age in keeping with physical and vascular ageing.
      As expected, aortic distensibility and PWV were closely correlated. These results
      demonstrate that PA patients display increased arterial stiffness compared with
      EH, independent of vascular ageing. The implication is that aldosterone invokes
      functional impairment of arterial function. The long-term implications of
      arterial stiffening in aldosterone excess require further study. 

PMID- 23884213
TI  - Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury.
AB  - Isoflurane is a volatile anesthetic that is widely used clinically as an
      inhalational anesthetic. In recent years, several studies have indicated that
      isoflurane has neuroprotective properties. This has led to the beneficial effects
      of isoflurane being analyzed in both cell culture and animal models, including
      various models of brain injury. Neonatal hypoxia ischemia may be characterized as
      injury that occurs in the immature brain, resulting in delayed cell death via
      excitotoxicity and oxidative stress. These adverse events in the developing brain
      often lead to detrimental neurological defects in the future. Currently, there
      are no well-established effective therapies for neonatal hypoxia ischemia. In
      line with this, isoflurane, which displays neuroprotective properties in several
      paradigms and has been shown to improve neurological deficits caused by brain
      injuries, has the capability to be an extremely relevant clinical therapy for the
      resolution of deficits concomitant with neonatal hypoxic ischemic brain injuries.
      This review therefore seeks to explore and analyze the current information on
      isoflurane, looking at general isoflurane anesthetic properties, and the
      protection it confers in different animal models, focusing particularly on
      neuroprotection as shown in studies with neonatal hypoxic ischemic brain injury. 

PMID- 23884214
TI  - Diffusion-controlled evolution of core-shell nanowire arrays into integrated
      hybrid nanotube arrays for Li-ion batteries.
AB  - Controlled integration of multiple semiconducting oxides into each single unit of
      ordered nanotube arrays is highly desired in scientific research for the
      realization of more attractive applications. We herein report a diffusion
      controlled solid-solid route to evolve simplex Co(CO3)0.5(OH)0.11H2O@TiO2 core
      shell nanowire arrays (NWs) into CoO-CoTiO3 integrated hybrid nanotube arrays
      (NTs) with preserved morphology. During the evolution procedure, the
      decomposition of Co(CO3)0.5(OH)0.11H2O NWs into chains of CoCO3 nanoparticles
      initiates the diffusion process and promotes the interfacial solid-solid
      diffusion reaction even at a low temperature of 450  degrees C. The resulting CoO
      CoTiO3 NTs possess well-defined sealed tubular geometries and a special "inner
      outer" hybrid nature, which is suitable for application in Li-ion batteries
      (LIBs). As a proof-of-concept demonstration of the functions of such hybrid NTs
      in LIBs, CoO-CoTiO3 NTs are directly tested as LIB anodes, exhibiting both a high
      capacity (~600 mA h g(-1) still remaining after 250 continuous cycles) and a much
      better cycling performance (no capacity fading within 250 total cycles) than CoO
      NWs. Our work presents not only a diffusion route for the formation of integrated
      hybrid NTs but also a new concept that can be employed as a general strategy to
      fabricate other oxide-based hybrid NTs for energy storage devices.

PMID- 23884215
TI  - NF-kappaB activation during intradermal DNA vaccination is essential for
      eliciting tumor protective antigen-specific CTL responses.
AB  - DNA vaccines have been shown to elicit tumor-protective cytotoxic T lymphocyte
      (CTL) immunity in preclinical models, but have shown limited efficacy in cancer
      patients. Plasmids used for DNA vaccines can stimulate several innate immune
      receptors, triggering the activation of master transcription factors, including
      interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kappaB).
      These transcription factors drive the production of type I interferons (IFNs) and
      pro-inflammatory cytokines, which promote the induction of CTL responses.
      Understanding the innate immune signaling pathways triggered by DNA vaccines that
      control the generation of CTL responses will increase our ability to design more
      effective vaccines. To gain insight into the contribution of these pathways, we
      vaccinated mice lacking different signaling components with plasmids encoding
      tyrosinase-related protein 2 (TRP2) or ovalbumin (OVA) using intradermal
      electroporation. Antigen-specific CTL responses were detected by intracellular
      IFN-gamma staining and in vivo cytotoxicity. Mice lacking IRF3, IFN-alpha
      receptor, IL-1beta/IL-18, TLR9 or MyD88 showed similar CTL responses to wild-type
      mice, arguing that none of these molecules were required for the immunogenicity
      of DNA vaccines. To elucidate the role of NF-kappaB activation we co-vaccinated
      mice with pIkappaBalpha-SR, a plasmid encoding a mutant IkappaBalpha that blocks
      NF-kappaB activity. Mice vaccinated with pIkappaBalpha-SR and the TRP2-encoding
      plasmid (pTRP2) drastically reduced the frequencies of TRP2-specific CTLs and
      were unable to suppress lung melanoma metastasis in vivo, as compared with mice
      vaccinated only with pTRP2. Taken together these results indicate that the
      activation of NF-kappaB is essential for the immunogenicity of intradermal DNA
      vaccines. 

PMID- 23884216
TI  - Atheroprotective Kruppel-like factor 4 is downregulated in monocyte subsets of
      patients with coronary artery disease.

PMID- 23884217
TI  - Serum methylmalonic acid and holotranscobalamin-II as markers for vitamin B12
      deficiency in end-stage renal disease patients.
AB  - BACKGROUND: Vitamin replacement, particularly B vitamins, remains an important
      concern in end-stage renal disease (ESRD) patients undergoing chronic
      hemodialysis. Serum markers such as methylmalonic acid (MMA) and
      holoTranscobalamin (holoTC) used to detect vitamin B12 deficiency are affected by
      impaired renal function which makes the interpretation of these biomarkers
      difficult in ESRD patients. We investigated the role renal failure has on MMA and
      holoTC concentrations and evaluated using MMA and/or holoTC to identify B12
      deficient patients. MATERIALS AND METHODS: We evaluated the utility of serum MMA
      and holoTC for its role in the detection of vitamin B12 deficiency in dialysis
      patients (n=17) by using the reduction of MMA concentrations as a marker of the
      response to vitamin B12 treatment (1 mg, intramuscular injections once per month
      for 3 months). Nerve conduction studies (NCS) were done before and after vitamin
      B12 treatments to evaluate for any alteration in peripheral sensorimotor nerve
      function within a subset of the cohort. RESULTS: Receiver operating
      characteristic curves for detection of vitamin B12 deficiency in dialysis
      patients showed that serum MMA concentrations had the greatest predictive
      potential (area under the curve = 0.792, p = 0.043) with an optimal cutoff of 750
      nmol/L. Dialysis patients (n=10) with pre-MMA > 750 nmol/L and pre-HoloTC < 260
      pmol/L showed a significant response to the vitamin B12 treatment (a mean MMA
      reduction of 461 nmol/L after B12 supplementation; p = 0.006). CONCLUSION: MMA is
      viable marker of B12 deficiency in ESRD patients. Holo TC has potential as a
      supplementary marker with MMA to predict the response of vitamin B12
      supplementation. Future studies on MMA and B12 should be done to confirm these
      findings in larger cohorts and to identify individuals who may benefit from
      vitamin B12 supplementation.

PMID- 23884218
TI  - Down-regulation of synaptotagmin 1 in cortex, hippocampus, and cerebellum after
      experimental subarachnoid hemorrhage.
AB  - Synapses are formed by the coordinated assembly and tight attachment of pre- and
      postsynaptic specializations. Synaptotagmin 1 (Syt 1) has been proven to be an
      important factor for synapse function and behavioral cognition. The current
      research was aimed to investigate the expression of Syt 1 in the brain after an
      experimental subarachnoid hemorrhage (SAH) in rats. A total of 42 rats were
      randomly divided into seven groups: normal group; control group; day 1, day 3,
      day 5, day 7 and day 14 groups. Day 1, day 3, day 5, day 7, and day 14 groups
      were all SAH groups in which the rats were killed on day 1, 3, 5, 7, and 14,
      respectively. The rat SAH model was induced by injection of 0.3 ml of fresh
      arterial, non-heparinized blood into the prechiasmatic cistern for 20 sec.
      Immunostaining and immunoblotting were performed to detect the expression of the
      Syt 1 protein. The expressions of the Syt 1 protein decreased remarkably in SAH
      groups compared to the control group. The down-regulated expression of Syt 1 was
      detected after SAH and the low ebb was on days 1-3. The immunohistochemical
      staining demonstrated the expression of Syt 1 to be present mainly in the neurons
      of the cortex, hippocampus, and cerebellum. Our results indicated that Syt 1
      expression is down-regulated in the brain after experimental SAH. These finding
      suggests that the decreased Syt 1 expression may facilitate the development of
      cognitive dysfunction after SAH. 

PMID- 23884219
TI  - EDA-containing fibronectin levels in the cerebrospinal fluid of children with
      meningitis.
AB  - Fibronectin containing an alternatively spliced extra domain A (EDA-FN)
      participates in diverse biological cell functions, being also directly or
      indirectly engaged during an inflammatory response to brain injury and/or neuron
      regeneration. We analyzed FN and EDA-FN isoform levels by ELISA in 85
      cerebrospinal fluid samples and 67 plasma samples obtained from children
      suffering from bacterial or viral meningitis and non-meningitis peripheral
      inflammation. We have found that the cerebrospinal level of EDA-FN was
      significantly lower in the bacterial meningitis group than in the viral- and non
      meningitis groups. In the patients' plasma, EDA-FN was almost undetectable. The
      determination of fibronectin containing the EDA segment might be considered as an
      additional diagnostic marker of bacterial meningitis in children. 

PMID- 23884220
TI  - Overnight storage of blood in ACD tubes at 4{degrees}C increases NK cell fraction
      in peripheral blood mononuclear cells.
AB  - A considerable variabilility in the effects of sample handling on NK cytotoxicity
      has been observed. Using flow cytometry, NK cytotoxicity assays and lymphocyte
      subset analysis of Ficoll-Hypaque-separated peripheral blood mononuclear cells
      (PBMCs) isolated from whole blood stored under various conditions were performed.
      The NK cytotoxicity of samples in heparin tubes stored overnight at 4 and 22
      degrees C, as well as at 22 degrees C in acid citrate dextrose (ACD) tubes, was
      lower than that of a fresh sample. However, the NK cytotoxicity of samples in an
      ACD tube stored at 4 degrees C was similar to that of a fresh sample. Based on
      lymphocyte subset analysis, samples in an ACD tube stored at 4 degrees C showed a
      lower percentage of CD3+ T cells and a higher percentage of CD16/56+ NK cells
      compared to samples stored under other conditions. The NK cytotoxicity of fresh
      samples and samples in ACD tubes stored in a Styrofoam cooler box did not differ
      significantly; however, the differences were inconsistent. Overnight storage of
      peripheral blood in ACD tubes at 4 degrees C is optimum for retention of NK
      cytotoxicity, the level of which is similar to that of fresh blood. This may be
      associated with an increased NK-cell fraction in Ficoll-Hypaque-separated PBMCs
      after overnight storage. 

PMID- 23884221
TI  - Effect of routine heparins treatment in acute coronary syndrome on serum
      pregnancy-associated plasma protein a concentration.
AB  - BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A) has been suggested as
      a useful marker of acute coronary syndrome (ACS). Serum PAPP-A concentrations are
      affected by unfractionated heparin (UFH) in ACS population, and we tried to
      investigate the time profile of effects of routine heparins treatment on serum
      PAPP-A concentrations in ACS population thoroughly and give advice to sample
      collection of related study. METHODS: Twenty cases were involved in this study:
      ten patients with acute myocardial infarction received subcutaneous low molecular
      weight heparin (LMWH) twice a day (group A), and the other ten percutaneous
      coronary intervention patients with stenting received intravenous UFH (group B).
      Samples were collected before and after heparin administration and serum PAPP-A
      concentrations were analyzed in these samples. RESULTS: Serum PAPP-A
      concentration increased in both group A and B. In group A, PAPP-A concentration
      elevated gradually (14.5 to 29.4 mIU/L, P<0.05) throughout the observation period
      and normalized at 48h after drug discontinuation. In group B, there was a rapid
      and intense increase after intravenous heparin injection (13.1 to 49.3 mIU/L,
      P<0.05), and a new PAPP-A peak was induced by additional heparin administration.
      CONCLUSIONS: Heparins-induced increase in serum PAPP-A concentration lasted until
      48h after drug use was discontinued. We recommend that samples from these
      patients for PAPP-A measurement should be collected at least 48h after the last
      administration if its not available before the administration of heparins.

PMID- 23884222
TI  - Comparison of glucose determinations on blood samples collected in three types of
      tubes.
AB  - Because of the metabolism of serum glucose in collection tubes containing blood
      samples, serum glucose levels may be found to decrease over time. Several types
      of collection tubes have been designed to, at least partially, block glucose
      metabolism by red blood cells in blood collection tubes that may not be analyzed
      immediately after blood collection. These include red-top collection tubes with
      serum separator, grey-top tubes with a fluoride glycolysis inhibitor, and heparin
      containing green-top tubes which prevent clot formation. As part of a quality
      assurance project, we investigated whether glucose levels differed in the three
      tube types from each of 18 volunteers on a prolonged standing of 4 hours. We then
      determined the glucose concentrations of all three tubes from each of the 18
      volunteers. We used refrigerated samples over a five-day period to determine if
      the initial values were reproducible. Surprisingly, after standing for four hours
      at room temperature, we found that the glucose levels in the three tubes from
      each volunteer were statistically indistinguishable from one another using the
      two-tailed paired t-test. Also, a linear regression analysis showed that the
      values of glucose for the three pairs of two tube types were closely correlated
      with one another, with correlation coefficients of >0.97, slopes close to 1, and
      Y-intercepts close to 0. These results suggest that blood collection in any of
      these tubes will render similar values for serum glucose even after standing for
      four hours. The tubes were then refrigerated at 4 degrees C and re-analyzed after
      another six hours and then once per day for the next four days. Beginning at the
      first day at the six-hour determination, the glucose levels in the red- and grey
      top tubes were statistically indistinguishable from one another but not in the
      red- and green-top tubes and in the grey- and green-top tubes. This was due to a
      steady decrease in the glucose levels in the green-top tubes. The glucose levels
      in the red- and grey-top tubes from each volunteer remained constant over the
      five-day period so that the coefficients of variation (CV) were low. In contrast,
      due to the decrease of glucose levels in the green-top tubes, the CVs for
      repeated glucose determinations in these tubes were high. Interestingly, a
      regression analysis of the glucose values for all three sets of paired tubes
      showed high (> 0.97) correlation coefficients and slopes close to 1. However, a
      regression analysis of the glucose values in the red- and green-top and grey- and
      green-top tubes at day five showed Y-intercepts of about -32 suggesting that
      there is a constant decrease of glucose in the green-top tubes that amounts to
      approximately 6 mg/dL per day over five days. These results suggest that red-top
      tubes with serum separator or grey-top tubes with a fluoride glycolysis inhibitor
      may be used for reproducible glucose determinations. 

PMID- 23884223
TI  - Interpretation and clinical significance of small monoclonal peaks in capillary
      electrophoresis.
AB  - BACKGROUND: Although the testing mechanism and interpretation criteria for
      capillary electrophoresis differ from those for gel-based electrophoresis, there
      are not that many reports on the efficacy of capillary electrophoresis. MATERIALS
      AND METHODS: We performed a retrospective analysis, using the Laboratory
      Information System (LIS) to review a total of 163 capillary electrophoresis
      results from 117 different patients treated in our hospital between March and
      August 2012. Capillary electrophoresis was performed on capillary2 (Sebia, Lysse,
      France). RESULTS: Among the patients' group, 4 patients presented very small M
      peaks in capillary electrophoresis. By using the zoom function in capillary
      electrophoresis, two of them were confirmed to have monoclonality, but the
      remaining two required reconfirmation in gel electrophoresis, leading to
      confirmation of a discrete monoclonal band. CONCLUSION: In this study, we found
      that small peaks in capillary electrophoresis accompanying a skewed K/L ratio
      deserve particular attention as they can grow into larger peaks within a few
      months. We suggest that any trivial M-peak in capillary electrophoresis should
      not be overlooked and that a combination of platform tests such as gel
      electrophoresis or FLC assay be implemented in order to confirm monoclonality.

PMID- 23884224
TI  - B-cell activating factor promoter polymorphisms in egyptian patients with
      systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogonous autoimmune
      disease involving most immune cells. Studies have revealed a number of cytokine
      pathways that play important roles in the disease process. Among these is B- cell
      activating factor (BAFF), which regulates B-cell maturation, survival, and
      function. OBJECTIVE: To study the association between BAFF promoter polymorphism
      and systemic lupus erythematosus (SLE). METHODS: Single nucleotide polymorphisms
      in the BAFF promoter region; -2841 (T>C), -2701 (T>A), -871 (C>T) were
      investigated by PCR-RFLP genotyping in fifty Egyptian SLE patients and thirty
      normal controls. RESULTS: The frequency of mutant alleles of both -871C>T and 
      2701 T>A was higher among SLE patients than controls (p-value <0.001 and 0.000
      respectively). There was a highly significant relationship between -871 C>T
      polymorphism and SLE (P<0.001), with the sensitivity and the specificity of the
      test being 100 %, and 70%, respectively. Patients expressing the -2701 T>A allele
      were seven times more prone to SLE than those with the T/T wild genotype
      (sensitivity of the test = 78%, specificity = 66.7%, odds ratio = 7.09, C.I at
      95% = 2.29-22.64). CONCLUSION: Polymorphisms in the regulatory region of the BAFF
      gene do contribute to the susceptibility to SLE in Egyptian patients, which
      indicates BAFF as a potential therapeutic target.

PMID- 23884226
TI  - Intravascular large B-cell lymphoma presenting as acute hemorrhagic cerebral
      infarct with delirium.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is a cumbersome diagnosis to make in
      vivo, particularly because of its elusive nature and ability to be a relatively
      nonspecific 'great mimicker'. Although it frequently has skin manifestations, it
      often escapes diagnosis due to its angiotrophism and predilection for vessels
      that are difficult to biopsy (e.g., cerebral vasculature). IVLBCL can involve the
      vasculature of virtually any organ but typically spares the lymph nodes
      themselves, and likely due to defects in adhesion molecules, remains stationary
      in the vessels. Histologically, the malignant lymphocytes are large and
      mitotically active with prominent nucleoli. Immunohistochemically, the cells
      stain as B-cells. The disease has an overall poor prognosis. Here we present a
      case of IVLBCL diagnosed at autopsy that presented as a hemorrhagic frontal lobe
      infarct, which progressed to delirium. 

PMID- 23884227
TI  - Three patients with glycogen storage disease type II and the mutational spectrum
      of GAA in Korean patients.
AB  - BACKGROUND: Glycogen storage disease II (GSD II) is caused by a deficiency of
      acid alpha-1,4-glucosidase and mutations in the GAA gene encoding this enzyme
      which are responsible for the pathogenesis of GSD II. Our goal was to determine
      the mutational spectrum in the GAA gene in Korean patients with GSD II. METHODS:
      Three patients with GSD II were recruited based on clinical and biochemical
      findings. Alpha-1,4-glucosidase activity was determined and the GAA gene sequence
      was analyzed by PCR and sequencing. We also collected information about the
      genotypes of Korean patients with GSD II from the medical literature. RESULTS: We
      identified six mutant alleles among the three GSD II patients: c.875A>G,
      c.1156C>T, c.1316T>A, c.1857C>G, and c2407_2412del7. c.1156C>T (Q386*) is a novel
      mutation. A comprehensive review of the literature revealed that a total of 29
      mutant alleles, including 15 different mutations (10 missense, 3 deletion, and 2
      nonsense mutations), were previously identified in 15 Korean GSD II patients.
      c.1316T>A (p.M439K) and c.1857C>G (p.S619R) were the most common mutations and
      accounted for 36.6% of the total mutant alleles. CONCLUSIONS: We identified three
      GSD II patients and investigated the mutational spectrum in GAA in Korean
      patients with GSD II. Our results indicate that common mutations in the GAA gene
      vary according to ethnic background.

PMID- 23884228
TI  - Morphoproteomic study of primary pleural angiosarcoma of lymphangioendothelial
      lineage: a case report.
AB  - An unusual case of bilateral primary pleural angiosarcoma with an immunophenotype
      of lymphangioendothelial lineage is described. Pleural angiosarcoma is a highly
      malignant neoplasm for which there is currently no standard of care. A
      comprehensive immunophenotypic characterization established a
      lymphangioendothelial lineage. A morphoproteomic analysis was also performed to
      identify the proteins and corresponding molecular pathways activated in the
      patient's tumor. The information derived from the morphoproteomic studies
      provides insight into the biology of the tumor and may be useful in formulating
      therapeutic alternatives. 

PMID- 23884225
TI  - Circulating tumor cells: a review of present methods and the need to identify
      heterogeneous phenotypes.
AB  - The measurement and characterization of circulating tumor cells (CTCs) hold
      promise for advancing personalized therapeutics. CTCs are the precursor to
      metastatic cancer and thus have the potential to radically alter patient
      treatment and outcome. Currently, clinical information provided by the
      enumeration of CTCs is limited to predicting clinical outcome. Other areas of
      interest in advancing the practice of pathology include: using CTCs for early
      detection of potential metastasis, determining and monitoring the efficacy of
      individualized treatment regimens, and predicting site-specific metastasis.
      Important hurdles to overcome in obtaining this type of clinical information
      involve present limitations in defining, detecting, and isolating CTCs.
      Currently, CTCs are detected using epithelial markers. The definition of what
      distinguishes a CTC should be expanded to include CTCs with heterogeneous
      phenotypes, and markers should be identified to enable a more comprehensive
      capture. Additionally, most methods available for detecting CTCs do not capture
      functionally viable CTCs. Retaining functional viability would provide a
      significant advantage in characterizing CTC-subtypes that may predict the site of
      metastatic invasion and thus assist in selecting effective treatment regimens. In
      this review we describe areas of clinical interest followed by a summary of
      current circulating cell-separation technologies and present limitations. Lastly,
      we provide insight into what is required to overcome these limitations as they
      relate to applications in advancing the practice of pathology and laboratory
      medicine. 

PMID- 23884229
TI  - Analysis of mutations in the XPD gene in a patient with brittle hair.
AB  - Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder
      characterized by sulfur-deficient brittle hair, growth and mental retardation,
      and ichthyosis. TTD is caused primarily by mutations in the xeroderma pigmentosum
      group D (XPD) gene, which encodes a subunit of the basal transcription factor
      IIH. We have identified a novel heterozygous mutation in XPD (c.1906C>T; p.R636W)
      resulting in mild-phenotype TTD in the proband and her mother. No identical
      variations were found in one hundred healthy Korean controls. In silico analysis
      suggested that the novel mutation was a causative mutation for TTD. This genotype
      phenotype correlation provides a unique insight into the TTD inheritance pattern
      and could prove useful in the diagnosis of patients. 

PMID- 23884230
TI  - Primary hyperoxaluria type 1 with systemic calcium oxalate deposition: case
      report and literature review.
AB  - We present an adult autopsy case of primary hyperoxaluria type 1. Diagnosis was
      established with skin biopsy and subsequent genetic analysis one month prior to
      death. At autopsy, calcium oxalate crystals refringent to polarized light were
      found systemically. Interestingly, however, calcium oxalate crystals were not
      identified in the bone. Additionally, we have included a review of the literature
      for previous autopsy cases, presentations, diagnosis, complications, and
      treatment of this rare genetic systemic process. 

PMID- 23884231
TI  - Clinical and cytogenetic features of a patient with partial trisomy 8q and
      partial monosomy 13q delineated by array comparative genomic hybridization.
AB  - Partial trisomy 8q is rare and has distinctive clinical features, including
      severe mental retardation, growth impairment, dysmorphic facial appearances,
      cleft palate, congenital heart disease, and urogenital anomalies. Partial
      monosomy 13q is a rare genetic disorder displaying a variety of phenotypic
      characteristics including mental retardation, dysmorphic facial features, and
      congenital anomalies. Here, we describe for the first time clinical observations
      and cytogenetic analysis of a patient with a concomitant occurrence of partial
      trisomy of 8q (8q21.3->qter) and partial monosomy 13q(13q34->qter). The patient
      was a female neonate with facial dysmorphia, agenesis of the corpus callosum,
      cleft palate, and congenital heart disease. G-band standard karyotype was
      46,XX,add(13)(q34). To determine the origin of additional genomic gain in
      chromosome 13, array comparative genomic hybridization (CGH) was performed. Array
      CGH showed a 56.8 Mb sized gain on chromosome 8q and a 0.28 Mb sized loss on
      chromosome 13q. Therefore, the final karyotype of the patient was defined as
      46,XX, der(13)t(8;13)(q21.3;q34). In conclusion, we described the clinical and
      cytogenetic analysis of the patient with concomitant occurrence of partial
      trisomy 8q and partial monosomy 13q delineated by array CGH. This report suggests
      that the array CGH would be a valuable diagnostic tool for identifying the origin
      of small additional genetic materials. 

PMID- 23884232
TI  - An abnormal elevation of serum CA72-4 by ganoderma lucidum spore powder.
AB  - We reported three patients with an abnormal elevation of serum CA72-4 levels when
      taking GLSP, which is commonly used as a dietary supplement for cancer patients
      across the globe. Furthermore, the results were not due to the apparent
      analytical interference. In case 1 and case 2, excessive examinations were
      carried out because of a lack of timely communication with patients when the
      abnormal elevation of CA724 was found. In contrast, the lesson from these two
      cases made us communicate with the patient in a timely manner in Case 3, avoiding
      unnecessary examinations when the same situation happened. Therefore, it is
      necessary to communicate with patients in a timely manner once an abnormal
      elevation of serum CA72-4 is found. 

PMID- 23884233
TI  - Temporal analysis of recruitment of mammalian ATG proteins to the autophagosome
      formation site.
AB  - Autophagosome formation is governed by sequential functions of autophagy-related
      (ATG) proteins. Although their genetic hierarchy in terms of localization to the
      autophagosome formation site has been determined, their temporal relationships
      remain largely unknown. In this study, we comprehensively analyzed the
      recruitment of mammalian ATG proteins to the autophagosome formation site by live
      cell imaging, and determined their temporal relationships. Although ULK1 and ATG5
      are separated in the genetic hierarchy, they synchronously accumulate at pre
      existing VMP1-positive punctate structures, followed by recruitment of ATG14,
      ZFYVE1, and WIPI1. Only a small number of ATG9 vesicles appear to be associated
      with these structures. Finally, LC3 and SQSTM1/p62 accumulate synchronously,
      while the other ATG proteins dissociate from the autophagic structures. These
      results suggest that autophagosome formation takes place on the VMP1-containing
      domain of the endoplasmic reticulum or a closely related structure, where ULK1
      and ATG5 complexes are synchronously recruited. 

PMID- 23884234
TI  - Necessity of performing I-131 MIBG post-therapy scans in patients with metastatic
      neuroblastoma.

PMID- 23884235
TI  - 3D-OSEM and FP-CIT SPECT quantification: benefit for studies with a high radius
      of rotation?
AB  - OBJECTIVES: Dopamine transporter imaging with single-photon emission computed
      tomography (SPECT) is a valuable tool for both clinical routine and research
      studies. Recently, it was found that the image quality could be improved by
      introduction of the three-dimensional ordered subset expectation maximization (3D
      OSEM) reconstruction algorithm, which provides resolution recovery. The aim of
      this study was to systematically evaluate the potential benefits of 3D-OSEM in
      comparison with 2D-OSEM under critical imaging conditions, for example, scans
      with a high radius of rotation. MATERIALS AND METHODS: Monte Carlo simulation
      scans of a digital brain phantom with various disease states and different radii
      of rotation ranging from 13 to 30 cm were reconstructed with both 2D-OSEM and 3D
      OSEM algorithms. Specific striatal binding and putamen-to-caudate ratios were
      determined and compared with true values in the phantom. RESULTS: The percentage
      recovery of true striatal binding was similar between both reconstruction
      algorithms at the minimum rotational radius; however, at the maximum rotational
      radius, it decreased from 53 to 43% for 3D-OSEM and from 52 to 26% for 2D-OSEM.
      3D-OSEM matched the true putamen-to-caudate ratios more closely than did 2D-OSEM
      in scans with high SPECT rotation radii. CONCLUSION: 3D-OSEM offers a promising
      image quality gain. It outperforms 2D-OSEM, particularly in studies with limited
      resolutions (such as scans acquired with a high radius of rotation) but does not
      improve the accuracy of the putamen-to-caudate ratios. Whether the benefits of
      better recovery in studies with higher radii of rotation could potentially
      increase the diagnostic power of dopamine transporter SPECT in patients with
      borderline striatal radiotracer binding, however, needs to be further examined.

PMID- 23884236
TI  - Inhibitory effects of epi-sesamin on endothelial protein C receptor shedding in
      vitro and in vivo.
AB  - OBJECTIVE AND DESIGN: Endothelial protein C receptor (EPCR) plays a pivotal role
      in augmenting Protein C activation by the thrombin-thrombomodulin complex. The
      activity of EPCR is markedly changed by ectodomain cleavage and release as the
      soluble protein (sEPCR). The EPCR shedding is mediated by the tumor necrosis
      factor-alpha converting enzyme (TACE). Epi-sesamin (ESM), from the roots of
      Asarum siebodlii, is known to exhibit anti-allergic and anti-fungal activities.
      However, little is known about the effects of ESM on EPCR shedding. METHODS: We
      investigated this issue by monitoring the effects of ESM on phorbol-12-myristate
      13-acetate (PMA), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and
      cecal ligation and puncture (CLP)-mediated EPCR shedding. RESULTS: Data showed
      that ESM induced potent inhibition of PMA, TNF-alpha, IL-1beta, and CLP-induced
      EPCR shedding, likely through suppression of TACE expression. In addition,
      treatment with ESM resulted in a reduction of PMA-stimulated phosphorylation of
      p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase
      (JNK). CONCLUSIONS: Given these results, ESM should be viewed as a candidate
      therapeutic agent for treatment of various severe vascular inflammatory diseases
      via inhibition of EPCR shedding.

PMID- 23884237
TI  - Shape-dependent electrocatalytic activity of monodispersed palladium nanocrystals
      toward formic acid oxidation.
AB  - The catalytic activity of different-shaped and monodispersed palladium
      nanocrystals, including cubes, octahedra and rhombic dodecahedra, toward the
      electrochemical oxidation of formic acid has been systematically evaluated in
      both HClO4 and H2SO4 solutions. Notably, the cubic palladium nanocrystals wholly
      exposed with {100} facets exhibit the highest activity, while the rhombic
      dodecahedra with {110} facets show the lowest electrocatalytic performance.
      Furthermore, compared with HClO4 electrolyte, the catalytic activity is found to
      be obviously lower in H2SO4 solution likely due to the competitive adsorption of
      SO4(2-) ions and formic acid on the surface of Pd nanocrystals. 

PMID- 23884238
TI  - Frequency of debridements and time to heal: a retrospective cohort study of 312
      744 wounds.
AB  - IMPORTANCE: Chronic wounds usually get trapped in the inflammatory stage of wound
      healing; however, aggressive debridement transforms chronic wounds to acute
      wounds and therefore complete healing. OBJECTIVE: To investigate healing outcomes
      and debridement frequency in a large wound data set. DESIGN: Retrospective cohort
      study. SETTING: Data collected from 525 wound care centers from June 1, 2008,
      through June 31, 2012, using a web-based clinical management system. PATIENTS:
      Referred sample of 154 644 patients with 312 744 wounds of all causes (of an
      initial data set of 364 534 wounds) participated. A total of 47.1% were male.
      Median age was 69 years (age range, 19-112 years), with 59.2% having one wound.
      Eligibility criteria included age older than 18 years, receiving at least 1
      debridement, and having been discharged from the system. Advanced therapeutic
      treatment was ineligible. Because of incomplete, questionable, or ineligible
      data, 57 190 wounds were not included. Most wounds were diabetic foot ulcers
      (19.0%), venous leg ulcers (26.1%), and pressure ulcers (16.2%). INTERVENTION:
      Debridement (removal of necrotic tissue and foreign bodies from the wound) at
      different frequencies. MAIN OUTCOME AND MEASURE: Wound healing (completely
      epithelialized with dimensions at 0 * 0 * 0 cm). RESULTS: A total of 70.8% of
      wounds healed. The median number of debridements was 2 (range, 1-138). Frequent
      debridement healed more wounds in a shorter time (P <  .001). In regression
      analysis, significant variables included male sex, physician category, wound
      type, increased patient age, and increased wound age, area, and depth. The odds
      ratio varied considerably for each variable. CONCLUSIONS AND RELEVANCE: The more
      frequent the debridements, the better the healing outcome. Although limited by
      retrospective data, this study's strength was the analysis of the largest wound
      data set to date.

PMID- 23884239
TI  - Cross reactivity of serum antibody responses elicited by DNA vaccines expressing
      HA antigens from H1N1 subtype influenza vaccines in the past 30 years.
AB  - In the past three decades, ten H1 subtype influenza vaccines have been
      recommended for global seasonal flu vaccination. Some of them were used only for
      one year before being replaced by another H1 flu vaccine while others may be used
      for up to seven years. While the selection of a new seasonal flu vaccine was
      based on the escape of a new emerging virus that was not effectively protected by
      the existing flu formulation, there is limited information on the magnitude and
      breadth of cross reactivity among H1 subtype virus circulation over a long
      period. In the current study, HA-expressing DNA vaccines were constructed to
      express individual HA antigens from H1 subtype vaccines used in the past 30 y.
      Rabbits naive to HA antibody responses were immunized with these HA DNA vaccines
      and the cross reactivity of these sera against HA antigen and related H1 viruses
      in the same period was studied. Our data indicate that the level of cross
      reactivity was different for different viral isolates and the key mutations
      responsible for the cross reactivity may involve only a limited number of
      residues. Our results provide useful information for the development of improved
      seasonal vaccines than can achieve broad protection against viruses within the
      same H1 subtype. 

PMID- 23884240
TI  - High-speed panoramic light-sheet microscopy reveals global endodermal cell
      dynamics.
AB  - The ever-increasing speed and resolution of modern microscopes make the storage
      and post-processing of images challenging and prevent thorough statistical
      analyses in developmental biology. Here, instead of deploying massive storage and
      computing power, we exploit the spherical geometry of zebrafish embryos by
      computing a radial maximum intensity projection in real time with a 240-fold
      reduction in data rate. In our four-lens selective plane illumination microscope
      (SPIM) setup the development of multiple embryos is recorded in parallel and a
      map of all labelled cells is obtained for each embryo in <10 s. In these
      panoramic projections, cell segmentation and flow analysis reveal characteristic
      migration patterns and global tissue remodelling in the early endoderm. Merging
      data from many samples uncover stereotypic patterns that are fundamental to
      endoderm development in every embryo. We demonstrate that processing and
      compressing raw image data in real time is not only efficient but indispensable
      for image-based systems biology.

PMID- 23884241
TI  - Amphiphiles in aqueous solution: well beyond a soap bubble.
AB  - Owing to their "dual" affinity, amphiphiles self-assemble in water to form
      different kinds of nanoscale multimolecular assemblies ranging from simple
      micelles and vesicles to highly organized fibers, helices and tubes. In this
      tutorial review the aggregates formed in water by head/tail amphiphiles are
      revisited and discussed from the point of view of supramolecular chemistry with a
      focus on their structure and recognition abilities. Their applications in
      materials chemistry, as soft templates for inorganic nanostructures, as well as
      in biological and medicinal chemistry are also illustrated. Special attention is
      paid to highlight intriguing aspects, for example the control of morphology and
      chirality, their modulation by experimental parameters and chiral symmetry
      breaking. 

PMID- 23884242
TI  - Grief and renewal: a clinician's journey.

PMID- 23884243
TI  - Fabrication of disposable gold macrodisc and platinum microband electrodes for
      use in room-temperature ionic liquids.
AB  - We report a simple and facile methodology for constructing gold macrodisc and
      platinum microband electrodes for use in room temperature ionic liquids (RTILs).
      To validate the use of gold macrodisc electrodes, the voltammetry of Ru(NH3)6(3+)
      was studied in 0.1 M aqueous KCl. The Randles-Sevcik equation was used to
      calculate the diffusion coefficient, giving excellent agreement with literature
      values, suggesting that the gold macrodisc electrode is capable of performing
      quantitative electroanalysis in aqueous media. Gold macrodisc electrodes were
      used to study oxidation of ferrocene in N-butyl-N-methylpyrrolidinium
      bis(fluoromethylsulfonyl)imide ([C4mpyrr][NTf2]) using cyclic voltammetry. The
      diffusion coefficient of ferrocene, (2.43 +/- 0.07) * 10(-11) m(2) s(-1), was
      obtained. This value is very close to the literature value, indicating good
      performance of gold electrodes in RTILs. Platinum microband electrodes were
      tested in 1-propyl-3-methylimidazolium bis-trifluoromethylsulfonylimide
      ([Pmim][NTf2]) containing decamethylferrocene. Diffusion coefficients and
      electron transfer rates were obtained by fitting relevant simulations to the
      experimental data. For comparison, analogous experiments and analyses were
      performed on a commercial platinum microdisc, where the results obtained from
      both microdisc and microband agree well, further suggesting that the platinum
      microband electrode is suitable to be used in RTILs. Finally, gold macrodisc and
      platinum microband electrodes were used for oxygen detection. Gold macrodisc
      electrodes were used to find the peak currents of oxygen at each volume
      percentage analysed. Platinum microband electrodes showed steady-state currents
      of different volumes of oxygen. These two results are compared which resulted in
      excellent agreement. This is further confirmed by studying Henry's law constants
      obtained from both electrodes. The excellent behaviour of these two fabricated
      electrodes suggests that they are suitable for quantitative measurements and
      practicable for real world applications. 

PMID- 23884244
TI  - Engaging students in the creation of a collaborative wiki textbook.

PMID- 23884246
TI  - Plakophilin 2 affects cell migration by modulating focal adhesion dynamics and
      integrin protein expression.
AB  - Plakophilin 2 (PKP2), a desmosome component, modulates the activity and
      localization of the small GTPase RhoA at sites of cell-cell contact. PKP2
      regulates cortical actin rearrangement during junction formation, and its loss is
      accompanied by an increase in actin stress fibers. We hypothesized that PKP2 may
      regulate focal adhesion dynamics and cell migration. Here we show that PKP2
      deficient cells bind efficiently to the extracellular matrix, but upon spreading
      display total cell areas ~ 30% smaller than control cells. Focal adhesions in
      PKP2-deficient cells are ~ 2 * larger and more stable than in control cells, and
      vinculin displays an increased time for fluorescence recovery after
      photobleaching. Furthermore, beta4 and beta1 integrin protein and mRNA expression
      is elevated in PKP2-silenced cells. Normal focal adhesion phenotypes can be
      restored in PKP2-null cells by dampening the RhoA pathway or silencing beta1
      integrin. However, integrin expression levels are not restored by RhoA signaling
      inhibition. These data uncover a potential role for PKP2 upstream of beta1
      integrin and RhoA in integrating cell-cell and cell-substrate contact signaling
      in basal keratinocytes necessary for the morphogenesis, homeostasis, and
      reepithelialization of the stratified epidermis.

PMID- 23884247
TI  - Inhibition of the prohormone convertase subtilisin-kexin isoenzyme-1 induces
      apoptosis in human melanoma cells.
AB  - Prohormone convertases (PCs) are endoproteases that process many substrates in
      addition to hormone precursors. Although overexpression of PCs is linked to
      carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1
      (SKI-1) in this context is unknown. We show that SKI-1 is constitutively
      expressed in human pigment cells with higher SKI activity in seven out of eight
      melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is
      also detectable in tumor cells of melanoma metastases. Moreover, tissue samples
      of the latter display higher SKI-1 mRNA levels and activity than normal skin.
      From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin
      affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable
      enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only
      suppressed proliferation and metabolic activity of melanoma cells in vitro but
      also reduced tumor growth of melanoma cells injected intracutaneously into
      immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces
      classical apoptosis of melanoma cells in vitro and affects expression of several
      SKI-1 target genes including activating transcription factor 6 (ATF6). However,
      ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting
      that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings
      encourage further studies on SKI-1 as a potential target for melanoma therapy. 

PMID- 23884248
TI  - Impact of aspirin dose on adenosine diphosphate-mediated platelet activities.
      Results of an in vitro pilot investigation.
AB  - Different aspirin dosing regimens have been suggested to impact outcomes when
      used in combination with adenosine diphosphate (ADP) P2Y12 receptor antagonists.
      Prior investigations have shown that not only aspirin, but also potent ADP P2Y12
      receptor blockade can inhibit thromboxane A2-mediated platelet activation. The
      impact of aspirin dosing on ADP mediated platelet activities is unknown and
      represents the aim of this in vitro pilot pharmacodynamic (PD) investigation.
      Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and
      P2Y12 naive were enrolled. PD assessments were performed at baseline, while
      patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 +/- 2
      days with and without escalating concentrations (vehicle, 1, 3, and 10 MUM) of
      prasugrel's active metabolite (P-AM). PD assays included flow cytometric
      assessment of VASP to define the platelet reactivity index (PRI) and the
      Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin
      (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations
      showed incremental platelet P2Y12 inhibition measured by VASP-PRI (p<0.001).
      However, there were no differences according to aspirin dosing regimen at any P
      AM concentration (vehicle: p=0.899; 1 MUM: p=0.888; 3 MUM: p=0.524; 10 MUM:
      p=0.548). Similar findings were observed in purinergic markers assessed by MEA
      (ADP and ADP+PGE1). P-AM addition significantly reduced AA and collagen induced
      platelet aggregation (p<0.001 for all measures), irrespective of aspirin dose. In
      conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated
      platelet reactivity irrespective of the degree of P2Y12 receptor blockade. P2Y12
      receptor blockade modulates platelet reactivity mediated by alternative
      activators. 

PMID- 23884249
TI  - Possible gadolinium ions leaching and MR sensitivity over-estimation in
      mesoporous silica-coated upconversion nanocrystals.
AB  - Mesoporous silica (m-SiO2) coated gadolinium (Gd) ions-doped upconversion
      nanoparticles (UCNPs) are regarded as one of most attractive nano-platforms which
      hold great potential in future cancer theranostics. The current general synthetic
      strategy for such promising structures includes the extraction of surfactant
      molecules in the final step. Here, in this article, we focus our interest on
      probing the potential influence of hydrochloric acid extraction on lanthanide
      ions leakage, MR sensitivity over-estimation and the optical intensity weakening
      of m-SiO2 coated Gd-doped UCNPs. Control experiments provide evidence of inner
      core damage, Gd(3+) ion release and residual Gd(3+) ions "trapped" within the
      core@shell structures. Our investigation shows that: (1) the small Gd-doped UCNPs
      could be fragile and sensitive to the hydrochloric acid-extraction and thermal
      treatment processes; and (2) the presence of "trapped" Gd(3+) ions not only
      provokes the concerns of potential cytotoxicity but also interfere with the
      contrast imaging tests of Gd-doped UCNPs, providing possible erroneous
      information on the determination of the longitudinal relaxivities of given
      probes. 

PMID- 23884250
TI  - Case reports deserve respect.

PMID- 23884251
TI  - Robotic-assisted laparoscopic hysterectomy: optimizing use of this technology.

PMID- 23884252
TI  - Isolated port-site metastasis after robotic hysterectomy for stage IA endometrial
      adenocarcinoma.
AB  - BACKGROUND: Port-site metastasis is a known complication of laparoscopic surgery,
      although it has been described less in robotic surgery. There are limited reports
      of such occurrences in current literature. CASES: Two patients underwent robotic
      assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and
      lymph node dissection for stage IA endometrial cancer. One patient's surgery was
      complicated by uterine perforation but the other surgery was uncomplicated. Both
      patients had development of isolated port-site metastasis and required resection
      followed by chemotherapy and radiation. CONCLUSION: Port-site metastasis is a
      surgical complication with an unclear etiology. There are no clear data to
      suggest a lower incidence with robotic surgery. Patients at low risk for
      recurrence still may experience development of port-site metastasis.

PMID- 23884253
TI  - Peripartum robotic-assisted laparoscopic hysterectomy after second-trimester
      pregnancy loss with placenta increta.
AB  - BACKGROUND: Peripartum hysterectomy is performed for a variety of indications,
      including abnormal placentation, retained placenta, uterine rupture, and uterine
      atony. Most cases are emergent and performed through open laparotomy. CASE: At 20
      weeks of gestation, a patient with previous endometrial ablation had ruptured
      membranes and delivered her fetus but not her placenta. She was hemodynamically
      stable and underwent robotic hysterectomy. Surgical pathology confirmed placenta
      increta. CONCLUSION: In appropriate patients, a minimally invasive approach may
      be considered for peripartum hysterectomy to potentially decrease maternal
      morbidity.

PMID- 23884254
TI  - Delayed diagnosis of vascular injury with a retropubic midurethral sling.
AB  - BACKGROUND: Retropubic midurethral slings are the mainstay of treatment for
      female stress urinary incontinence. Complications of this approach may have long
      term implications. CASE: A 55-year-old woman underwent tension-free vaginal tape
      (TVT) placement. Five years later back pain and gross hematuria prompted
      cystoscopy and diagnosis of bladder mesh erosion. During surgery to remove the
      mesh, the left arm of the mesh was found to be through the external iliac vein.
      The right mesh arm traversed the bladder, laterally around the obturator nerve
      and right iliac vein, exiting through the peritoneal cavity. CONCLUSION:
      Neurovascular injury is a rare but serious consequence of TVT. Delayed diagnosis
      is possible. This case highlights the importance of using recognized landmarks
      and established surgical technique for TVT placement.

PMID- 23884255
TI  - Nonsurgical management of a rectovaginal fistula caused by a Gellhorn pessary.
AB  - BACKGROUND: Pessaries are generally thought to be a safe, well-tolerated
      treatment for pelvic organ prolapse. CASE: An 85-year-old woman had a Gellhorn
      pessary placed for pelvic organ prolapse. Although she was seen regularly for
      care, the pessary had not been removed for several years. She presented stating
      that she felt the pessary had shifted. On examination, the patient's pessary stem
      had eroded through the vagina into the rectum. The pessary was removed and the
      patient was treated with vaginal estradiol cream. One month later the fistula
      tract had resolved and the patient continued to desire a pessary to manage her
      pelvic organ prolapse. CONCLUSION: Pessaries require care and maintenance.
      Patients' desires for conservative management should be coupled with education
      and routine follow-up.

PMID- 23884256
TI  - Vulvar histoplasmosis as a rare cause of genital ulceration.
AB  - BACKGROUND: Histoplasmosis is an infection caused by the dimorphic fungus
      Histoplasma capsulatum and primarily presents with pulmonary symptoms.
      Immunocompromised individuals are at high risk for contracting disseminated
      histoplasmosis, which can be fatal if left untreated. CASE: We present a case
      involving a 50-year-old woman with acquired immunodeficiency syndrome with an
      ulcerated vulvar lesion concerning for carcinoma. Extensive workup revealed
      disseminated histoplasmosis without pulmonary manifestations. She was treated
      with an extended course of an antifungal agent. Her vulvar lesion resolved.
      CONCLUSION: Vulvar histoplasmosis is a rare etiology of vulvar pathology but one
      that should be considered in immunocompromised patients.

PMID- 23884257
TI  - Vulvar pyoderma gangrenosum originating from a healed obstetric laceration.
AB  - BACKGROUND: Pyoderma gangrenosum is a rare dermatologic disorder that can occur
      on the vulva. CASE: A 25-year-old woman, gravida 2 para 1 abortus 1, had
      development of pain and subsequent ulceration at the location of her previously
      healed vulvar obstetric laceration. The ulceration and pain continued to worsen
      despite wound management. Once the diagnosis of vulvar pyoderma gangrenosum was
      made, cyclosporine was started and the wound rapidly healed. CONCLUSION: Vulvar
      pyoderma gangrenosum should be considered when a vulvar wound is not healing with
      conservative measures. Cyclosporine can be considered as an alternative to
      steroids for treatment.

PMID- 23884258
TI  - Idiopathic CD4 lymphocytopenia manifesting as refractory genital dysplasia.
AB  - BACKGROUND: Idiopathic CD4 lymphocytopenia is an immunodeficiency disorder with
      low absolute CD4 T-lymphocyte count with no evidence of human immunodeficiency
      virus or other known cause. CASE: A 22-year-old woman presented with a high-grade
      Pap test result. Work-up demonstrated cervical intraepithelial neoplasia 3 and
      vaginal intraepithelial neoplasia 3 with extensive condyloma. She presented 6
      months after her initial treatment with recurrent disease and was referred to the
      immunology department, where she was found to have profound lymphopenia. After
      further evaluation, idiopathic CD4 lymphocytopenia was diagnosed. CONCLUSION:
      Idiopathic CD4 lymphocytopenia is a rare acquired immunodeficiency. Although
      genital dysplasia is common in young women, this case demonstrates the importance
      of determining other etiologies of recurrent human papillomavirus infections and
      possible immunodeficiencies that may affect management and outcomes.

PMID- 23884259
TI  - Secondary infertility and retained fetal bone fragments.
AB  - BACKGROUND: Retained fetal bone fragments may be an underreported and
      underappreciated cause of secondary infertility among women with an antecedent
      spontaneous or induced abortion. CASES: Three patients with a history of an
      antecedent induced abortion presented with secondary infertility. The infertility
      evaluation diagnosed retained intrauterine fetal bone fragments. After removal of
      the bone fragments, two of the three patients successfully conceived. CONCLUSION:
      Secondary infertility may be the only presenting symptom for women with retained
      fetal bone fragments. Women with secondary infertility and antecedent spontaneous
      or induced abortion may benefit from uterine evaluation with ultrasonography
      before initiating infertility treatment. For patients with findings of focal
      echogenic shadowing lesions at ultrasonography, we recommend ultrasonography
      guided hysteroscopy to ensure that bone fragments embedded within the myometrium
      are not missed and are completely resected.

PMID- 23884260
TI  - Management of interstitial ectopic pregnancies with a combined intra-amniotic and
      systemic approach.
AB  - BACKGROUND: Approximately 2% of all pregnancies are ectopic; of these, 4% are
      interstitial or cervical. There exists no clear consensus as to whether surgical
      or medical management is superior. CASE: We present three cases of advanced
      nonfallopian tube ectopic pregnancies from 6 to 8 weeks of gestation. Our first
      two cases were managed with a combined intrafetal, intra-amniotic and systemic
      approach using methotrexate and potassium chloride, whereas our third case was
      managed with an intra-amniotic approach alone. Our combined approach cases were
      successful, with resolution of human chorionic gonadotropin in 50 and 34 days,
      whereas our single approach case re-presented with bleeding requiring uterine
      artery embolization and operative removal of products of conception. CONCLUSION:
      Patients presenting with advanced interstitial or cervical pregnancies who are
      clinically stable can be offered medical management with a combined approach.

PMID- 23884261
TI  - Maternal bladder cancer diagnosed at routine first-trimester obstetric ultrasound
      examination.
AB  - BACKGROUND: Bladder cancer is exceedingly rare in pregnancy and most commonly
      presents with gross hematuria. CASES: We describe two patients with the
      incidental finding of maternal bladder masses identified during routine first
      trimester obstetric ultrasonographic evaluation and an ultimate diagnosis of
      carcinoma. After referral for urology evaluation and biopsy confirmation of
      bladder cancer, patients underwent surgical resection during their pregnancies
      without the need for further treatment and had uncomplicated pregnancy courses.
      CONCLUSION: The distended maternal urinary bladder at the time of first-trimester
      ultrasonographic evaluation offers a unique opportunity for examination and early
      diagnosis of incidental maternal bladder carcinoma.

PMID- 23884262
TI  - Resection of urethral diverticulum in pregnancy.
AB  - BACKGROUND: Female urethral diverticulum is a rare finding, less often diagnosed
      during pregnancy. There are few reports in the literature on urethral
      diverticulum in pregnancy with most undergoing expectant management. CASE: A
      young woman presented during the third trimester of pregnancy with pelvic and
      vaginal pain and a vaginal bulge. On examination, she was noted to have a 5-cm
      periurethral mass consistent with a urethral diverticulum. We describe the
      successful excision of this diverticulum during pregnancy. CONCLUSION: The
      procedure was performed without adverse consequences to the pregnancy, and the
      patient had a normal course for the remainder of her pregnancy and an uneventful
      cesarean delivery.

PMID- 23884263
TI  - Urachal duct carcinoma complicating pregnancy.
AB  - BACKGROUND: Degenerating myomas are common explanations for pain associated with
      abdominal masses in pregnancy. However, masses arising from other pelvic organs
      should be included in the differential diagnosis. CASE: We present a case of an
      abdominal mass in pregnancy that was originally misdiagnosed as a uterine
      leiomyoma. Attention to the patient's history along with judicious use of imaging
      modalities led to the correct diagnosis of urachal duct carcinoma. This was
      treated appropriately and resulted in a term vaginal delivery. We present a
      review of the literature on this tumor and its management in pregnancy.
      CONCLUSION: Urologic malignancies are rare but should be considered in the
      differential diagnosis for any woman presenting with pain and an abdominal mass
      in pregnancy. A multidisciplinary approach optimizes outcomes.

PMID- 23884264
TI  - Rupture of an unscarred uterus in a woman with long-term steroid treatment for
      systemic lupus erythematosus.
AB  - BACKGROUND: Unscarred uterine rupture in association with systemic lupus
      erythematosus (SLE) and long-term steroid treatment is rare. CASE: A 36-year-old
      primigravid woman conceived a twin gestation after in vitro fertilization
      therapy. At 23 weeks of gestation, she was found to have a spontaneous rupture of
      the uterus. Her medical history was significant for SLE for a duration of 19
      years, and her condition had been maintained with prednisolone. She had no
      history of uterine scarring or other known risk factors for uterine rupture. The
      uterine fundus was the main location of the rupture and a subtotal hysterectomy
      was performed. CONCLUSION: Long-term treatment with systemic steroids and SLE may
      increase the risk of spontaneous rupture of an unscarred uterus.

PMID- 23884265
TI  - Uterine rupture after prior conservative management of placenta accreta.
AB  - BACKGROUND: There is little evidence for counseling patients who seek uterine
      conservation in the setting of placenta accreta. CASE: We report the case of a 37
      year-old woman with retained placenta accreta after vaginal delivery. Attempts at
      transvaginal removal failed, and the placenta was removed through a fundal
      hysterotomy with bilateral uterine artery ligations performed to control blood
      loss. She conceived a second pregnancy 11 months later and sustained spontaneous
      fundal uterine rupture at 26.5 weeks of gestation with a recurrent accreta found
      at the rupture site. The newborn survived but has residual musculoskeletal
      morbidity and developmental delay at 1 year of age. CONCLUSION: Patients
      undergoing conservative treatment of placenta accreta in the setting of a fundal
      hysterotomy should be cautioned about recurrent accreta and uterine rupture.

PMID- 23884266
TI  - Placenta increta after hysteroscopic myomectomy.
AB  - BACKGROUND: Most cases of abnormal placentation are associated with a history of
      one or more cesarean deliveries. Uterine leiomyomas and treatment for such a
      diagnosis are also risk factors for placenta accreta and should be viewed as
      such. CASE: A 34-year-old woman underwent a hysteroscopic myomectomy and became
      pregnant 6 months later. Ultrasonography and magnetic resonance imaging suggested
      a placenta percreta. Multidisciplinary care allowed for a safe delivery of her
      neonate and little maternal morbidity. CONCLUSION: Patients with a history of
      hysteroscopic myomectomy or other uterine leiomyoma treatment are at an increased
      risk for abnormal placentation. Imaging studies are suggested in such patients to
      coordinate multidisciplinary care to decrease maternal and fetal morbidity and
      mortality.

PMID- 23884267
TI  - Intraperitoneal chemotherapy in a pregnant woman with ovarian cancer.
AB  - BACKGROUND: Ovarian cancer diagnosed in pregnancy is rare. There is limited
      evidence to guide the choice of optimal chemotherapeutic management for treatment
      of disease during pregnancy. CASE: A 36-year-old primigravid woman was diagnosed
      with stage IIB grade III serous adenocarcinoma at 12 weeks of gestation. After
      extensive counseling, she opted for intraperitoneal chemotherapy. She received
      four cycles during the course of the pregnancy, and treatment was complicated by
      thrombocytopenia and mild preeclampsia. Delivery occurred by cesarean at 37 weeks
      of gestation, resulting in the birth of a live male neonate weighing 4 pounds 11
      ounces with bilateral congenital talipes equinovarus. CONCLUSION: Pregnant women
      with ovarian cancer should be offered the opportunity to maximize their survival,
      including standard chemotherapeutic regimens used in nonpregnant patients.

PMID- 23884268
TI  - Use of a thrombopoietin mimetic for chronic immune thrombocytopenic purpura in
      pregnancy.
AB  - BACKGROUND: Romiplostim, a thrombopoietin mimetic, is a novel therapeutic option
      for patients with chronic immune thrombocytopenic purpura. We report on the
      effects of romiplostim use throughout pregnancy. CASE: A 28-year-old primigravid
      woman with chronic immune thrombocytopenic purpura initiated a planned pregnancy
      on romiplostim. The second and third trimesters were marked by a cyclic pattern
      of thrombocytopenia requiring supplemental corticosteroids or intravenous
      immunoglobulin and resultant thrombocytosis. Increased romiplostim doses and
      daily corticosteroids stabilized the platelet count before induction of labor at
      33 weeks of gestation. The newborn manifested intraventricular hemorrhage at
      birth, although no developmental delay was present on follow-up at 10 months of
      age. CONCLUSION: The decreased efficacy of romiplostim monotherapy is attributed
      to increased target-mediated drug disposition and the physiologic changes of
      pregnancy. Safety concerns still exist for the developmental effects of
      romiplostim on the fetus.

PMID- 23884269
TI  - Cabergoline therapy for Cushing disease throughout pregnancy.
AB  - BACKGROUND: Cushing disease during pregnancy is rare and is associated with
      significant maternal and fetal morbidity and mortality. Transsphenoidal pituitary
      surgery is the first-line therapy; however, in cases of failed surgery or in
      patients who are not surgical candidates, medical therapy has been used to
      control symptoms. CASE: A 29-year-old woman with Cushing disease and a
      noncurative transsphenoidal pituitary surgery was successfully treated with
      cabergoline, a dopamine agonist. After approximately 1 year of therapy, she
      became pregnant. She was maintained on high-dose cabergoline throughout her
      pregnancy and had an uncomplicated antenatal course. She went into spontaneous
      labor at 38 weeks of gestation and delivered a healthy female neonate.
      CONCLUSION: Cabergoline can be used to manage Cushing disease successfully during
      pregnancy with an opportunity for a favorable outcome.

PMID- 23884270
TI  - Eculizumab for atypical hemolytic uremic syndrome in pregnancy.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (HUS) is a thrombotic
      microangiopathy often caused by mutations in complement genes. During pregnancy,
      disease outcome is poor both for mother and fetus. Since 2009, the humanized
      monoclonal antibody eculizumab has been successfully used in the treatment of
      atypical HUS in nonpregnant patients. CASE: A 26-year-old woman with a homozygous
      mutation in complement factor H developed a relapse of atypical HUS at 17 weeks
      of gestation in her first pregnancy. Because the disease remained active despite
      multiple plasma exchanges, eculizumab was started at 26 weeks of gestation. It
      was well tolerated and has led to remission and to the delivery of a healthy
      neonate. CONCLUSION: Eculizumab may be useful for the treatment of atypical HUS
      during pregnancy.

PMID- 23884271
TI  - Thionamide-induced neutropenia and ecthyma in a pregnant patient with
      hyperthyroidism.
AB  - BACKGROUND: Agranulocytosis is known to be a rare side effect of thionamides.
      This complication puts pregnant patients at particular risk for infections.
      Obstetricians caring for such patients have the difficult task of deciding
      between conservative or surgical management. CASE: The patient is a 37-year-old
      gravida 4 para 3 Hispanic woman at 11 weeks of gestation with recently diagnosed
      hyperthyroidism who presented with a neutropenic fever and ecthyma as a
      complication of thionamide use. She subsequently underwent a thyroidectomy and
      then had a spontaneous abortion on postoperative day 2. CONCLUSION: This patient
      had life-threatening thyrotoxicosis complicated by neutropenic fever and
      infection, likely caused by a reaction to thionamides. She quickly recovered with
      broad-spectrum antibiotics. She could not be restarted on methimazole or
      propylthiouracil as a result of agranulocytosis and thus underwent thyroidectomy.

PMID- 23884272
TI  - Maternal rhabdomyolysis and twin fetal death associated with gestational diabetes
      insipidus.
AB  - BACKGROUND: Gestational diabetes insipidus is a rare, transient complication of
      pregnancy typically characterized by polyuria and polydipsia that may lead to
      mild electrolyte abnormalities. More severe sequelae of gestational diabetes
      insipidus are uncommon. CASE: We present a case of a 25-year-old woman at 23
      weeks of gestation in a dichorionic-diamniotic twin pregnancy who developed
      severe symptomatic gestational diabetes insipidus complicated by rhabdomyolysis
      and death of both fetuses. CONCLUSION: Maternal rhabdomyolysis caused by
      gestational diabetes insipidus is extremely rare. Early recognition and treatment
      of gestational diabetes insipidus is necessary to prevent maternal and fetal
      morbidity and mortality.

PMID- 23884273
TI  - Baking soda pica associated with rhabdomyolysis and cardiomyopathy in pregnancy.
AB  - BACKGROUND: Pica is a commonly underappreciated disorder in pregnancy that can
      lead to several complications, including severe metabolic derangements and other
      adverse outcomes. We report a case of baking soda pica in pregnancy associated
      with both rhabdomyolysis and cardiomyopathy. CASE: A multigravid woman at 37
      weeks of gestation presented with weakness and severe hypokalemia. She
      subsequently had development of rhabdomyolysis and presumed peripartum
      cardiomyopathy. After delivery, it was discovered that the patient had a long
      history of consumption of large quantities of baking soda. Her condition improved
      with cessation of the pica. CONCLUSION: Clinicians must have a high index of
      suspicion for pica in pregnancy because it can lead to complex diagnostic
      challenges and pregnancy complications. The diagnosis should be considered in a
      patient with unexplained metabolic abnormalities.

PMID- 23884274
TI  - Maternal coagulopathy after umbilical cord occlusion for twin reversed arterial
      perfusion sequence.
AB  - BACKGROUND: Twin reversed arterial perfusion sequence is a rare complication of
      monochorionic twin gestations for which therapy involves the disruption of
      vascular anastomoses between the pump twin and acardiac twin and death of the
      acardius. CASE: A 37-year-old woman, gravida 11 para 2, with a monochorionic twin
      pregnancy complicated by twin reversed arterial perfusion sequence who underwent
      umbilical cord occlusion at 24 weeks of gestation was admitted in preterm labor
      at 33 weeks of gestation. Maternal disseminated intravascular coagulation (DIC)
      was diagnosed and her labor was induced. She received multiple blood products to
      correct her coagulopathy and had an uncomplicated vaginal delivery of the viable
      pump twin. CONCLUSION: Maternal DIC may complicate fetal death after umbilical
      cord occlusion.

PMID- 23884275
TI  - Lethal neonatal coagulopathy after maternal ingestion of a superwarfarin.
AB  - BACKGROUND: Brodifacoum, a superwarfarin, is a common household agent used for
      rodenticides. We present a case of maternal brodifacoum ingestion that resulted
      in neonatal death. CASE: A 19-year-old primigravid woman presented at 32 weeks of
      gestation with spontaneous mucosal bleeding. Her fetus showed evidence of
      acidosis on external fetal monitoring. Laboratory values were consistent with
      maternal coagulopathy. After correction of the coagulopathy, the patient was
      taken for urgent cesarean delivery. The neonate showed evidence of fetal
      coagulopathy and died at 4 days of life. CONCLUSION: Brodifacoum is a dangerous
      household chemical that, if ingested, can result in significant morbidity and
      mortality for both mother and neonate. Increased awareness of the serious and
      potentially lethal effects of brodifacoum is important.

PMID- 23884276
TI  - Vitamin K deficiency bleeding and early infant male circumcision in Africa.
AB  - BACKGROUND: Early infant (1-60 days of life) male circumcision is being trialed
      in Africa as a human immunodeficiency virus prevention strategy. Postcircumcision
      bleeding is particularly concerning where most infants are breastfed, and thus
      these infants are at increased risk of vitamin K deficiency bleeding. CASE:
      During a circumcision trial, one infant bled for 90 minutes postprocedure. After
      discovering he had not received standard prophylactic vitamin K, we gave 2 mg
      phytomenadione (vitamin K1) intramuscularly; bleeding stopped within 30 minutes.
      CONCLUSION: Vitamin K's extremely rapid action is not commonly appreciated.
      Neonatal vitamin K has been shown to be cost-effective. To increase availability
      and promote awareness of its importance, especially in low-resource settings
      where blood products and transfusions are limited, vitamin K should be included
      in the World Health Organization's Model List of Essential Medicines for
      Children.

PMID- 23884277
TI  - Malignant pulmonary edema in a pregnant woman caused by cor triatriatum.
AB  - BACKGROUND: Undiagnosed maternal congenital heart disease can result in
      significant risks to both mother and fetus. When maternal symptoms and signs are
      atypical of preeclampsia, broadening the differential diagnosis and
      multidisciplinary consultation can lead to improved outcomes. CASE: A 24-year-old
      primiparous woman with a pregnancy complicated by elevated blood pressure and
      proteinuria presented at term with symptoms of decreased fetal movement,
      increasing dyspnea, and cough. Her symptoms progressively worsened until she
      experienced cardiorespiratory arrest during attempted intubation. Emergency
      cesarean delivery was performed after 5 minutes of resuscitation efforts.
      Echocardiogram performed after delivery revealed cor triatriatum requiring
      surgical excision. CONCLUSION: A complete differential diagnosis for edema,
      hypertension, and dyspnea near term will allow for recognition of more rare
      conditions. Referral to cardiology in cases in which work-up is negative for
      preeclampsia may aid in earlier diagnosis and management. A team approach to
      management involving obstetrics and medicine will improve the rapidity with which
      rare conditions can be managed effectively.

PMID- 23884278
TI  - Reversed end-diastolic flow in the middle cerebral artery preceding death in a
      normally grown fetus.
AB  - BACKGROUND: Reversed diastolic flow in the middle cerebral artery has been
      described as a terminal sign in the growth-restricted fetus. The implication of
      this in a normally grown fetus is unknown. CASE: Middle cerebral artery Doppler
      velocimetry was performed at 28 weeks of gestation in the setting of decreased
      fetal movement and a category 2 fetal heart tracing. The middle cerebral artery
      pulsatility index was elevated, and follow-up studies revealed reversed flow. The
      fetus had appropriate growth, with mild polyhydramnios and no signs of
      cardiomegaly, effusion, or hydrops. Fetal death was diagnosed 4 days later in the
      setting of extensive intracranial hemorrhage. CONCLUSION: Regardless of fetal
      growth, persistent reversed middle cerebral artery Doppler with an elevated
      pulsatility index may be a feature of impending death.

PMID- 23884279
TI  - A metabolic scenario for the evolutionary origin of peroxisomes from the
      endomembranous system.
AB  - A novel model for the evolutionary origin of peroxisomes and related organelles
      from within the endoplasmic reticulum is proposed. 

PMID- 23884280
TI  - Gated SPECT evaluation of left ventricular function using a CZT camera and a fast
      low-dose clinical protocol: comparison to cardiac magnetic resonance imaging.
AB  - PURPOSE: CZT technology allows ultrafast low-dose myocardial scintigraphy but its
      accuracy in assessing left ventricular function is still to be defined. METHODS:
      The study group comprised 55 patients (23 women, mean age 63 +/- 9 years)
      referred for myocardial perfusion scintigraphy. The patients were studied at rest
      using a CZT camera (Discovery NM530c; GE Healthcare) and a low-dose (99m)Tc
      tetrofosmin clinical protocol (mean dose 264 +/- 38 MBq). Gated SPECT imaging was
      performed as a 6-min list-mode acquisition, 15 min after radiotracer injection.
      Images were reformatted (8-frame to 16-frame) using Lister software on a Xeleris
      workstation (GE Healthcare) and then reconstructed with a dedicated iterative
      algorithm. Analysis was performed using Quantitative Gated SPECT (QGS) software.
      Within 2 weeks patients underwent cardiac magnetic resonance imaging (cMRI, 1.5-T
      unit CVi; GE Healthcare) using a 30-frame acquisition protocol and dedicated
      software for analysis (MASS 6.1; Medis). RESULTS: The ventricular volumes
      obtained with 8-frame QGS showed excellent correlations with the cMRI volumes
      (end-diastolic volume (EDV), r = 0.90; end-systolic volume (ESV), r = 0.94; p <
      0.001). However, QGS significantly underestimated the ventricular volumes (mean
      differences: EDV, -39.5 +/- 29 mL; ESV, -15.4 +/- 22 mL; p < 0.001). Similarly,
      the ventricular volumes obtained with 16-frame QGS showed an excellent
      correlations with the cMRI volumes (EDV, r = 0.92; ESV, r = 0.95; p < 0.001) but
      with significant underestimations (mean differences: EDV, -33.2 +/- 26 mL; ESV, 
      17.9 +/- 20 mL; p < 0.001). Despite significantly lower values (47.9 +/- 16 % vs.
      51.2 +/- 15 %, p < 0.008), 8-frame QGS mean ejection fraction (EF) was closely
      correlated with the cMRI values (r = 0.84, p < 0.001). The mean EF with 16-frame
      QGS showed the best correlation with the cMRI values (r = 0.91, p < 0.001) and
      was similar to the mean cMRI value (49.6 +/- 16 %, p not significant). Regional
      analysis showed a good correlation between both 8-frame and 16-frame QGS and cMRI
      wall motion score indexes (8-frame WMSI, r = 0.85; 16-frame WMSI, r = 0.89; p <
      0.01). CONCLUSION: Low-dose gated SPECT with a CZT camera provides ventricular
      volumes that correlate well with cMRI results despite significant underestimation
      in the measure values. EF estimation appeared to be more accurate with 16-frame
      reformatted images than with 8-frame images.

PMID- 23884281
TI  - Cell pairing using a dielectrophoresis-based device with interdigitated array
      electrodes.
AB  - We present a chip device with an array of 900 gourd-shaped microwells designed to
      pair single cells of different types. The device consists of interdigitated array
      (IDA) electrodes and uses positive dielectrophoresis to trap cells within the
      microwells. Each side of a microwell is on a different comb of the IDA, so that
      cells of different types are trapped on opposite sides of the microwells, leading
      to close cell pairing. Using this device, a large number of cell pairs can be
      formed easily and rapidly, making it a highly attractive tool for controllable
      cell pairing in a range of biological applications. 

PMID- 23884282
TI  - Value of magnetic resonance diffusion-weighted imaging for the prediction of
      radiosensitivity in nasopharyngeal carcinoma.
AB  - OBJECTIVE: The effectiveness of radiotherapy in nasopharyngeal carcinoma (NPC) is
      closely related to the radiosensitivity of the carcinoma; however, there is
      currently no effective method to predict radiosensitivity in NPC. We explored the
      predictive value of magnetic resonance diffusion-weighted imaging (MR-DWI) for
      radiosensitivity in NPC. Study Design Prospective cohort study. Setting Single
      hospital. SUBJECTS AND METHODS: Patients with NPC who received intensity
      modulated radiotherapy (IMRT) with or without chemotherapy were enrolled from
      April 2010 through November 2011. Primary tumor apparent diffusion coefficient
      (ADC) was measured before treatment (ADC0) and 2 weeks after the start of IMRT
      (ADC1). ADC change (DeltaADC) was calculated as (ADC1 - ADC0)/ADC0 * 100%. Three
      months after the end of radiotherapy, the short-term effect of radiotherapy was
      assessed using the World Health Organization's response evaluation criteria in
      solid tumors. RESULTS: Of 134 eligible NPC patients, 121 received combination
      chemotherapy. Three months after radiotherapy, residual local tumors were
      detected in 23 (17.2%) cases, and no residual tumors were detected in 111 (82.8%)
      cases. There was no significant difference in the residual tumor rates of
      patients receiving combination chemotherapy vs those who did not (P = 1.000).
      There were no significant differences in the ADC0 or ADC1 values of patients with
      and without residual tumors (P = .083 and .262). The DeltaADC values of patients
      with (49.77% +/- 31.02%) and without (68.35% +/- 34.22%) residual tumors were
      significantly different (t = -2.406, P = .017). Logistic regression analysis
      indicated that DeltaADC was an independent prognostic factor for the short-term
      effect of IMRT in NPC. CONCLUSION: Magnetic resonance diffusion-weighted imaging
      may potentially have value for predicting radiosensitivity in NPC.

PMID- 23884283
TI  - Chronic rhinosinusitis in children: race and socioeconomic status.
AB  - PURPOSE: Although chronic rhinosinusitis (CRS) is common in children, the
      influence of race and socioeconomic status (SES) on the diagnosis/treatment of
      CRS has not been evaluated. We describe the epidemiology of children with CRS in
      a pediatric otolaryngology clinic and evaluate demographic differences when
      compared to a group of children referred for a general pediatric otolaryngology
      evaluation. STUDY DESIGN: Historical cohort study. SETTING: Tertiary academic
      care center. SUBJECTS AND METHODS: All new/consult patients (March 1, 2008-July
      1, 2011) in a tertiary pediatric otolaryngology clinic with primary diagnosis of
      CRS were compared to a control group that consisted of all new/consult patients
      seen in the same clinic over 3 months. Records were evaluated for variables
      including age, sex, race, and insurance. Characteristics were compared between
      groups using Mann-Whitney and Fisher's exact tests. RESULTS: One hundred and
      seventy-four children with CRS were compared to 430 controls. When compared to
      the general pediatric otolaryngology population, children with CRS were older
      (8.2 +/- 4.4 years vs 5.9 +/- 4.8 years; P < .0001) and more commonly male (63%
      vs 52%; P = .018). When compared to controls, children with CRS were more likely
      to be white (CRS 77% white, 10% black, 13% other vs control 47% white, 33% black,
      20% other; P < .0001, risk ratio [RR] = 2.7; 95% confidence interval [CI], 2.0
      3.7). Likewise, children with CRS were less commonly insured with medical
      assistance (CRS 14% vs control 44%; P < .0001; RR = 0.3; 95% CI, 0.21-0.45).
      CONCLUSIONS: When compared to the general population of children seen in this
      academic urban pediatric otolaryngology setting, children with CRS were more
      likely to be white and privately insured. This study is the first to evaluate
      race and SES in relationship to pediatric CRS. Future research should employ
      nationally representative data to assess the true demographic variation in
      children with CRS.

PMID- 23884284
TI  - Velopharyngeal incompetence as a complication of Grisel syndrome.

PMID- 23884285
TI  - Flap selection and functional outcomes in total glossectomy with laryngeal
      preservation.
AB  - OBJECTIVE: Reconstruction of total glossectomy defects has been revolutionized by
      the popularity of free flap use in the head and neck. Challenging defects can be
      addressed with a variety of different free and pedicled flaps. The purpose of
      this study is to review our method of flap selection in cases of total
      glossectomy defects with laryngeal preservation, with an emphasis on the
      variations of these defects and patient body habitus. STUDY DESIGN: Case series
      with chart review. SETTING: Tertiary care referral center. SUBJECTS AND METHODS:
      All patients undergoing total glossectomy with laryngeal preservation (TGLP) by
      the senior author (YD) from September 1997 to May 2012. Objective data regarding
      patient demographics, existing defect, method of reconstruction, adjuvant
      treatment, operative details, outcomes, and complications were recorded. Both
      means and frequency of prolonged tracheostomy or gastrostomy tube were used to
      assess outcomes. RESULTS: One hundred and three patients were identified. Ninety
      four met inclusion criteria. All patients were T3 or T4 stage tumors. Mean follow
      up was 3.4 years. Fifty-nine patients (62%) underwent free flap reconstruction
      while the remaining 35 (37%) were treated with a pedicled pectoralis myocutaneous
      flap. Tracheostomy decannulation and gastrostomy tube removal rates were 84% and
      29%, respectively. No patients were converted to total laryngectomy. CONCLUSION:
      Optimal reconstruction of TGLP defects may be accomplished with either pedicled
      or free-tissue flap reconstruction. Selecting an ideal flap for reconstruction of
      total glossectomy defects should be patient specific and based on matching donor
      flap bulk. This treatment approach demonstrates high tracheostomy and gastric
      tube independence.

PMID- 23884286
TI  - Osteopontin does not mitigate cisplatin ototoxicity or nephrotoxicity in adult
      mice.
AB  - OBJECTIVE: The goal of this study was to determine whether osteopontin, a
      molecule with a variety of biologic effects including cell death inhibition,
      plays an important role in protection of the inner ear and kidney from the toxic
      effects of the chemotherapeutic drug cisplatin. STUDY DESIGN: In vivo study using
      a model system of cisplatin toxicity in adult mice. SETTING: Virginia Merrill
      Bloedel Hearing Research Center, University of Washington. SUBJECTS AND METHODS:
      Osteopontin+/+ and Osteopontin-/- adult mice were treated with intraperitoneal
      cisplatin (20 mg/kg) or saline (control). Osteopontin levels were investigated by
      immunohistochemistry. Auditory brainstem response thresholds and cochlear
      histology were used to assess ototoxicity, while serum creatinine and renal
      histology were used to assess nephrotoxicity. For quantitative experiments, 8 to
      18 animals were included in each treatment group. RESULTS: At 72 hours after
      cisplatin treatment, there was a slight increase in osteopontin levels within the
      kidney but not in the inner ear. There was no difference in auditory brainstem
      response threshold shifts, outer hair cell death, or serum creatinine between
      Osteopontin+/+ and Osteopontin-/- mice. Cochlear and renal histologic damage
      following cisplatin appeared to be similar in Osteopontin+/+ and Osteopontin-/-
      mice. CONCLUSION: Osteopontin is not required for development of normal auditory
      or renal function. Osteopontin is unlikely to play a role in protection of the
      inner ear or kidney from acute cisplatin toxicity. Slight increases in renal
      osteopontin 72 hours after cisplatin injury may be important for regeneration of
      proximal tubule cells.

PMID- 23884287
TI  - Highly selective fluorescent sensing for CN- in water: utilization of the
      supramolecular self-assembly.
AB  - A simple 4-amino-3-hydroxynaphthalene-1-sulfonic acid is demonstrated to
      fluorescently sense CN(-) in water based on the mechanism of supramolecular self
      assembly. This work provides a novel approach for the selective recognition of
      CN(-) anions. The detection limit of the sensor towards CN(-) is 3.2 * 10(-7) M,
      and other anions, including F(-), Cl(-), Br(-), I(-), AcO(-), H2PO4(-), HSO4(-)
      and ClO4(-), had nearly no influence on the probing behavior. Notably, the test
      strips based on S4 were fabricated, which could act as convenient and efficient
      CN(-) test kits. 

PMID- 23884288
TI  - Observation of cation ordering and anion-mediated structure selection among the
      layered double hydroxides of Cu(II) and Cr(III).
AB  - Highly ordered Cl(-) and SO4(2-)-intercalated layered double hydroxides (LDHs) of
      Cu(II) and Cr(III) are obtained when coprecipitation is carried out at low pH ~ 5
      and elevated temperature (60-80  degrees C). Precipitation under other conditions
      results in the formation of a gel. The SO4(2-)-LDH exhibits weak reflections
      which could be indexed to the 100 and 101 planes of a supercell corresponding to
      a = ?3 *a(o), providing direct evidence for cation ordering among LDHs by X-ray
      diffraction. The ordering of the M(II) and M'(III) in the metal hydroxide layer
      has been a subject of considerable debate in the LDH literature for the past
      several years and was earlier probed using short-range techniques such as NMR and
      EXAFS. Rietveld refinement indicates that the cation-ordered LDH adopts the
      structure of the 1H polytype (space group P3] a = 5.41 A, c = 11.06 A). In
      contrast the Cl(-)-intercalated LDH adopts the cation-disordered structure of the
      3R1 polytype (space group R3[combining macron]m, a = 3.11 A, c = 23.06 A). The
      Cl(-)-LDH was used as a precursor to synthesize LDHs with other anions. While Br(
      ) and CO3(2-) (molecular symmetry, D3h) select for the 3R1 polytype, the XO3(-)
      (X = Br, I) ions (molecular symmetry, C3v) select for the rare 3R2 polytype. This
      work demonstrates the role of the intercalated anion in structure selection of
      the LDH.

PMID- 23884289
TI  - Hyperthin nanochains composed of self-polymerizing protein shackles.
AB  - Protein fibrils are expected to have applications as functional nanomaterials
      because of their sophisticated structures; however, nanoscale ordering of the
      functional units of protein fibrils remains challenging. Here we design a series
      of self-polymerizing protein monomers, referred to as protein shackles, derived
      from modified recombinant subunits of pili from Streptococcus pyogenes. The
      monomers polymerize into nanochains through spontaneous irreversible covalent
      bond formation. We design the protein shackles so that their reactions can be
      controlled by altering redox conditions, which affect disulphide bond formation
      between engineered cysteine residues. The interaction between the monomers
      improves their polymerization reactivity and determines morphologies of the
      polymers. In addition, green fluorescent protein-tagged protein shackles can
      polymerize, indicating proteins can be stably attached to the nanochains with its
      functionality preserved. Furthermore we demonstrate that a molecular-recognizable
      nanochain binds to its partner with an enhanced binding ability in solution.
      These characteristics are expected to be applied for novel protein nanomaterials.

PMID- 23884290
TI  - Is there an association between clinical presentation and the location and extent
      of myocardial involvement of cardiac sarcoidosis as assessed by 18F-
      fluorodoexyglucose positron emission tomography?
AB  - BACKGROUND: Positron emission tomography using (18)F-Fluorodeoxyglucose (FDG) is
      an emerging modality for diagnosis of cardiac sarcoidosis (CS). We compared the
      location and degree of FDG uptake in CS patients presenting with either advanced
      atrioventricular block (AVB) or ventricular tachycardia (VT). METHODS AND
      RESULTS: We included consecutive patients who presented with either AVB or VT
      with a diagnosis of CS. A cohort of patients with clinically silent CS was
      included as controls. FDG activity was quantified as standardized uptake values
      (SUV) and both the overall mean left ventricular (LV) SUV as well as the Maximum
      Mean Segmental SUV was recorded for each patient. Receiver operator
      characteristic (ROC) analysis was performed to identify cutoff SUV values that
      best identified patients with VT. A total of 27 patients with CS were included
      (13 females; mean age, 56 +/- 8 years; 8 VT, 12 AVB, and 7 controls). Both mean
      LV SUV and Max SUV in CS patients presenting with VT were significantly higher
      compared with those with AVB (mean SUV: VT median 5.33, range 4.7-9.35 versus AVB
      median 2.48, range 0.86-8.59, P=0.016; max SUV: VT median 11.07, range 9.24-14.4
      versus AVB median 5.63, range 3.42-15.71, P=0.005) and compared with controls.
      There was no significant difference in SUV values between AVB patients and
      controls. ROC analysis for identification of patients with VT showed AUCs of 0.93
      and 0.895 for a mean LV SUV of >3.42 and a max SUV >8.56, respectively (P<0.001).
      CONCLUSIONS: CS patients with VT displayed significantly higher FDG uptake when
      compared with those with AVB and asymptomatic controls. Further prospective
      studies are required to evaluate this finding.

PMID- 23884291
TI  - Integrated approach to treatment-resistant atrial fibrillation: additional value
      of acupuncture.
AB  - A 62-year-old patient with chronic bronchitis had treatment-resistant atrial
      fibrillation. Electrical cardioversion was performed, but sinus rhythm (SR)
      lasted only for some minutes. Administration of amiodarone was withheld in favour
      of a course of acupuncture treatment in order to increase the success rate of a
      second attempt of electrical cardioversion. After two acupuncture treatments,
      spontaneous conversion to SR occurred. Relapses into atrial fibrillation in the
      following five winters, associated with attacks of bronchitis, also responded to
      acupuncture. The mechanisms of action of the acupuncture treatment and the value
      of this integrated approach to treatment are discussed. 

PMID- 23884292
TI  - Catalytic MBH reaction of beta-substituted nitroalkenes with azodicarboxylates.
AB  - An unprecedented N-heterocyclic carbene (NHC) catalyzed Morita-Baylis-Hillman
      (MBH) reaction of beta-substituted nitroalkenes and azodicarboxylates has been
      developed. Both beta-aryl and beta-alkyl nitroalkenes worked well for the
      reaction using 5 mol% of NHC catalyst, giving the desired alpha-hydrazino
      alpha,beta-unsaturated nitroalkenes in good to excellent yields. 

PMID- 23884294
TI  - Treating large pulmonary emboli: do the guidelines guide us?
AB  - PURPOSE OF REVIEW: The diagnosis and management of patients with large pulmonary
      emboli can be confusing. This review will summarize available data and suggest
      the areas of certainty and uncertainty in the treatment of these patients. RECENT
      FINDINGS: Pulmonary emboli can be stratified according to patient prognosis. Risk
      stratification of patients with submassive pulmonary emboli is still lacking.
      Similarly, although the treatment of low-risk pulmonary embolism is well
      established, and there is consensus regarding systemic thrombolysis for unstable
      patients with pulmonary embolism, the management of patients with submassive
      pulmonary embolism is still a matter of debate. The role of novel approaches such
      as low-dose thrombolysis, catheter-directed therapies and advanced
      cardiopulmonary support is yet to be determined. Although some patients in
      skilled centers may benefit from pulmonary embolectomy, patient selection has yet
      to be refined. SUMMARY: The treatment of massive and submassive pulmonary
      embolism has yet to be standardized. The complexity in choosing appropriate
      treatments for these patients is due to the lack of high-quality data compounded
      by an expanding arsenal of therapeutic options.

PMID- 23884293
TI  - Novel insights into breast cancer genetic variance through RNA sequencing.
AB  - Using RNA sequencing of triple-negative breast cancer (TNBC), non-TBNC and HER2
      positive breast cancer sub-types, here we report novel expressed variants,
      allelic prevalence and abundance, and coexpression with other variation, and
      splicing signatures. To reveal the most prevalent variant alleles, we overlaid
      our findings with cancer- and population-based datasets and validated a subset of
      novel variants of cancer-related genes: ESRP2, GBP1, TPP1, MAD2L1BP, GLUD2 and
      SLC30A8. As a proof-of-principle, we demonstrated that a rare substitution in the
      splicing coordinator ESRP2 (R353Q) impairs its ability to bind to its substrate
      FGFR2 pre-mRNA. In addition, we describe novel SNPs and INDELs in cancer relevant
      genes with no prior reported association of point mutations with cancer, such as
      MTAP and MAGED1. For the first time, this study illustrates the power of RNA
      sequencing in revealing the variation landscape of breast transcriptome and
      exemplifies analytical strategies to search regulatory interactions among cancer
      relevant molecules. 

PMID- 23884295
TI  - Nonsteroidal therapy of sarcoidosis.
AB  - PURPOSE OF REVIEW: None of the medications used in clinical practice to treat
      sarcoidosis have been approved by the regulatory authorities. Understanding how
      to use disease-modifying antisarcoid drugs, however, is essential for physicians
      treating patients with sarcoidosis. This review summarizes the recent studies of
      medications used for sarcoidosis with a focus on nonsteroidal therapies. Studies
      from 2006 to 2013 were considered for review to update clinicians on the most
      relevant literature published over the last few years. RECENT FINDINGS: Several
      recently published pieces of evidence have helped expand our ability to more
      appropriately sequence second-line and third-line therapies for sarcoidosis. For
      instance, methotrexate and azathioprine may be useful and well tolerated
      medications as second-line treatment. Mycophenolate mofetil might have a role in
      neurosarcoidosis. TNF-alpha blockers and other biologics seem to be well
      tolerated medications for the most severely affected patients. SUMMARY:
      Corticosteroids remain the first-line therapy for sarcoidosis as many patients
      never require treatment or only necessitate a short treatment duration. Second
      line and third-line therapies described in this article should be used in
      patients with progressive or refractory disease or when life-threatening
      complications are evident at the time of presentation.

PMID- 23884296
TI  - Enhancing the accuracy of echocardiography in the diagnosis of pulmonary arterial
      hypertension: looking at the heart to learn about the lungs.
AB  - PURPOSE OF REVIEW: Although routine use of Doppler echocardiography has led to an
      increased recognition of pulmonary hypertension, the role of Doppler
      echocardiography has largely remained as a screening tool with the primary
      emphasis on the presence or absence of an increased Doppler-estimated pulmonary
      artery systolic pressure (PASP). However, the utility of Doppler echocardiography
      in the workup of pulmonary hypertension extends far beyond that of a screening
      tool, with the integration of relevant Doppler echocardiography parameters
      providing a wealth of hemodynamic insight into not only if a patient has
      pulmonary hypertension, but why they have pulmonary hypertension. This review
      summarizes some of the recent advances in the use of Doppler echocardiography in
      evaluating the pathophysiology of pulmonary hypertension. RECENT FINDINGS:
      Distinguishing pulmonary hypertension related to pulmonary vascular disease (i.e.
      pulmonary arterial hypertension, pulmonary hypertension due to lung disease, or
      chronic thromboembolic pulmonary hypertension; PHPVD), from those with left heart
      disease associated pulmonary hypertension (pulmonary venous hypertension; PVH) is
      crucial as workup and treatment options differ dramatically. Recent studies have
      identified easily obtainable Doppler echocardiography parameters that can
      reliably distinguish between PHPVD and PVH, allowing for rapid triage of patients
      with evidence of PHPVD to invasive right heart catheterization whiles avoiding
      invasive investigation and the inappropriate use of pulmonary hypertension
      specific therapy in patients with PVH. SUMMARY: This review highlights the
      importance of integrating two-dimensional and Doppler parameters in order to
      inform the clinician as to the hemodynamic cause of pulmonary hypertension, thus
      enhancing the diagnostic accuracy of Doppler echocardiography, rapidly
      identifying those with PHPVD and right heart dysfunction and assisting in triage
      of patients to further invasive hemodynamic assessment.

PMID- 23884297
TI  - Activation of Rho GTPase Cdc42 promotes adhesion and invasion in colorectal
      cancer cells.
AB  - BACKGROUND: The purpose of this study was to investigate the role of activated
      Rho GTPase cell division control protein 42 homolog (Cdc42) in colorectal cancer
      cell adhesion, migration, and invasion. MATERIAL AND METHODS: The constitutively
      active form of Cdc42 (GFP-Cdc42L61) or control vector was overexpressed in the
      colorectal cancer cell line SW480. The localization of active Cdc42 was monitored
      by immunofluorescence staining, and the effects of active Cdc42 on cell migration
      and invasion were examined using an attachment assay, a wound healing assay, and
      a Matrigel migration assay in vitro. RESULTS: Immunofluorescence staining
      revealed that constitutively active Cdc42 predominately localized to the plasma
      membrane. Compared to SW480 cells transfected with the control vector,
      overexpression of constitutively active Cdc42 in SW480 cells promoted filopodia
      formation and cell stretch and dramatically enhanced cell adhesion to the coated
      plates. The wound healing assay revealed a significant increase of migration
      capability in SW480 cells expressing active Cdc42 compared to the control cells.
      Additionally, the Matrigel invasion assay demonstrated that active Cdc42
      significantly promoted SW480 cell migration through the chamber. CONCLUSIONS: Our
      results suggest that active Rho GTPase Cdc42 can greatly enhance colorectal
      cancer cell SW480 to spread, migrate, and invade, which may contribute to
      colorectal cancer metastasis.

PMID- 23884298
TI  - Use of a gyroscope sensor to quantify tibial motions during a pivot shift test.
AB  - PURPOSE: The purpose of this preliminary study was to evaluate the use of a
      gyroscope sensor to record rotations of the tibia about its long axis during a
      clinical pivot shift examination. METHODS: Ten patients with a unilateral ACL
      injury were tested under anaesthesia prior to surgery. Each ankle was placed in
      neutral position, wrapped and stabilized with athletic tape, and a small
      aluminium plate was taped to the bottom of the foot. A data recovery module was
      attached to the bottom of each plate using a swivel bracket that allowed
      alignment of the gyro axis with the long axis of the tibia. The module contained
      a triaxial gyroscope, battery and circuitry for wireless data broadcast to a
      laptop computer. Ten pivot shift tests were performed on both knees, and the
      surgeon's clinical grading of the pivot shift was noted for each limb. Mean
      values (10 trials) of peak tibial rotational velocity and integrated tibial
      rotation were compared between knees for each patient during the pivot shift
      reduction event (external tibial rotation during knee flexion). RESULTS: Five
      patients (50%) had significantly greater tibial rotation in their injured knee,
      four showed no difference between knees, and one had significantly greater
      rotation in the normal knee (p < 0.05). Seven patients (70%) showed greater peak
      rotational velocity in their injured knee, and three had no difference between
      the knees (p < 0.05). Correlations of rotation and rotational velocity with
      clinical pivot shift grade were weak (r2 = 0.09 and 0.19, respectively).
      CONCLUSIONS: Foot gyroscope measurements did not correctly identify the injured
      limb in all patients. Peak rotational velocity during the reduction event was a
      better indicator of ACL deficiency than the integrated rotation. If this
      technology is to be more useful clinically, gyroscope data may have to be
      combined with accelerometer data, perhaps with sensors mounted on both the tibia
      and femur. LEVEL OF EVIDENCE: Diagnostic case-control study, Level III.

PMID- 23884299
TI  - 1H-magnetic resonance spectroscopy in diffuse and focal cervical cord lesions in
      multiple sclerosis.
AB  - OBJECTIVES: To investigate differences between focal and diffuse cervical lesions
      in multiple sclerosis (MS) by proton magnetic resonance spectroscopy ((1)H-MRS)
      at 1.5 T in comparison to quantitative MR imaging of the upper cervical cord area
      and T2 relaxometry at baseline and follow-up. METHODS: Including 22 MS patients
      with persistent spinal cord symptoms by either diffuse or focal lesions and 17
      controls, we acquired MRS, the mean cord area and the water T2 relaxation time
      and disability at baseline and follow-up. Cross-sectional analyses included group
      level comparisons and correlation studies. Follow-up studies covered assessment
      of reproducibility and progression of the baseline results. RESULTS: Compared
      with focal lesions, diffuse lesions were attended by more cord atrophy, longer
      T2, elevated levels of creatine (Cre) and reduced N-acetyl aspartate (NAA)/Cre
      (focal/diffuse: 83 +/- 9/73 +/- 15 mm(2), 121 +/- 21/104 +/- 13 ms, 3.6 +/-
      1.1/5.1 +/- 2.4 mM, 2.4 +/- 1.1/2.0 +/- 0.9). NAA/Cre at baseline was associated
      significantly with cord atrophy and with clinical progression during follow-up.
      Baseline MRS results were not significantly correlated to the clinical disability
      parameters. The reproducibility of MRS was 0.17-0.30. Longitudinal changes of the
      MRS results were not statistically significant. CONCLUSIONS: MRS indicated
      differences in demyelination and gliosis between diffuse and focal cervical
      lesions in MS. Although longitudinal spectral and clinical changes were sparse,
      NAA/Cre turned out to be the most sensitive spectral parameter.

PMID- 23884300
TI  - Whole-body diffusion-weighted imaging: is it all we need for detecting metastases
      in melanoma patients?
AB  - OBJECTIVES: To investigate whether whole-body diffusion-weighted imaging (WB-DWI)
      alone is adequate for detecting metastases in melanoma patients, or if standard
      WB contrast-enhanced magnetic resonance imaging (WB-ceMRI) is required. METHODS:
      Seventy-one WB-DWI studies were performed quarterly along with whole-body MRI
      including contrast-enhanced sequences (WB-ceMRI) in 19 patients with advanced
      melanoma. The reference standard was biopsy, other imaging investigations, or
      changes observed on follow-up. Findings of metastasis in separate WB-DWI and WB
      DWI + WB-ceMRI readings were compared using kappa statistics. Additionally, the
      distribution of findings was examined and calculated per body region (brain,
      neck, chest, abdomen, liver, pelvis, subcutaneous tissues, bones) and diagnostic
      accuracy (DA), sensitivity, specificity, negative predictive value, and positive
      predictive value were calculated per patient. RESULTS: The eight examinations
      that were positive by the reference standard contained a total of 14 metastatic
      findings. With almost perfect agreement between techniques (kappa = 85 %, 95 % CI
      70-100 %) for detection of examinations with metastatic findings, and complete
      agreement in extracranial metastasis detection, 10 metastases were detected using
      WB-DWI and 13 using WB-DWI + WB-ceMRI. WB-DWI and WB-DWI + WB-MRI had equivalent
      per patient DA (79 %). CONCLUSIONS: WB-DWI without additional WB-ceMRI sequences
      is promising for the detection of extracranial metastases in melanoma patients,
      but contrast-enhanced MRI is required for evaluating the brain.

PMID- 23884302
TI  - Should the duodenum be "the road less traveled" for biliary reconstruction?

PMID- 23884301
TI  - MRI and suspected acute pyelonephritis in children: comparison of diffusion
      weighted imaging with gadolinium-enhanced T1-weighted imaging.
AB  - OBJECTIVES: To evaluate the performance of diffusion-weighted imaging (DWI)
      against the reference standard of gadolinium-enhanced T1-weighted imaging (Gd-T1
      WI) in children. METHODS: Thirty-nine consecutive patients (mean age 5.7 years)
      with suspected acute pyelonephritis underwent magnetic resonance imaging (MRI)
      including DWI and (the reference standard) Gd-T1-WI. Each study was read in
      double-blinded fashion by two radiologists. Each kidney was graded as normal or
      abnormal. Sensitivity and specificity of DWI were computed. Agreement between
      sequences and interobserver reproducibility were calculated (Cohen kappa
      statistic and the McNemar tests). RESULTS: Thirty-two kidneys (41 %) had hypo
      enhancing areas on Gd-T1-W images. The sensitivity and specificity of DWI were
      100 % (32/32) and 93.5 % (43/46). DWI demonstrated excellent agreement (kappa =
      0.92,) with Gd-T1-W, with no significant difference (P = 0.25) in detection of
      abnormal lesions. Interobserver reproducibility was excellent with DWI (kappa =
      0.79). CONCLUSION: DWI enabled similar detection of abnormal areas to Gd-T1-WI
      and may provide an injection-free means of evaluation of acute pyelonephritis.
      KEY POINTS: * Diffusion weighted magnetic resonance imaging (DWI) can confirm
      acute pyelonepritis. * DWI provided comparable results to gadolinium enhanced T1
      W MRI in acute pyelonepritis. * Contrast medium injection could be avoided for
      diagnosing acute pyelonephritis by MRI. * MRI with T2-WI and DWI provide a fast
      and comprehensive diagnostic tool.

PMID- 23884303
TI  - Dabigatran monitoring made simple?

PMID- 23884304
TI  - Preparation of porous polymer monolithic column using functionalized graphene
      oxide as a functional crosslinker for high performance liquid chromatography
      separation of small molecules.
AB  - A newly developed porous polymer monolith was prepared through copolymerization
      of 3-(trimethoxysilyl)propylmethacrylate modified graphene oxide with glycidyl
      methacrylate and ethylene dimethacrylate as a functional crosslinker, which was
      synthesized through silanization reaction of graphene oxide prepared by Hummers
      method with 3-(trimethoxysilyl)propylmethacrylate. The monolith was characterized
      by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy,
      transmission electron microscopy, scanning electron microscopy, mercury intrusion
      porosimetry and nitrogen adsorption measurement. The monolith column was applied
      as the stationary phase of high performance liquid chromatography and its
      chromatographic performance was evaluated by separation of small molecules in the
      isocratic reversed-phase mode. The chromatograms of hydrophobic steroids and
      polar aromatic amines on the prepared monolith displayed the enhanced separation
      performance over those on the parent monolith. The reproducibility of the column
      was less than 3.5% in terms of relative standard deviation of retention time. The
      results demonstrate that copolymerization of functionalized graphene oxide into
      porous polymer monolith was an effective tool for chromatography separation
      enhancement of small molecules in an isocratic mode. 

PMID- 23884305
TI  - Effect of excessive contralateral trunk tilt on pitching biomechanics and
      performance in high school baseball pitchers.
AB  - BACKGROUND: There is a growing number of pitching-related upper extremity
      injuries among young baseball pitchers; however, there is a lack of data on the
      identification of injury prevention strategies, particularly the prevention of
      injuries through the instruction/modification of technique. The identification of
      technical parameters that are associated with increased joint loading is needed.
      PURPOSE: To investigate the effects of excessive contralateral trunk tilt, a
      common technique identifiable by video observation, on pitching biomechanics and
      performance in high school baseball pitchers. The hypothesis was that this
      strategy is associated with greater joint loading and poor pitching performance.
      STUDY DESIGN: Descriptive laboratory study; Level of evidence, 3. METHODS: The 3
      dimensional pitching biomechanics, ball speed, and frontal view of the pitching
      technique from 72 high school baseball pitchers were captured on video and
      analyzed. The videos were reviewed to determine if the pitcher's trunk was
      excessively contralaterally tilted at the instant of maximal shoulder external
      rotation by examining whether the side of the pitcher's head ipsilateral to the
      throwing limb deviated by more than a head width from a vertical line passing
      through the pitcher's stride foot ankle. Upper extremity kinetics and upper
      extremity/trunk kinematics between pitchers with and without excessive
      contralateral trunk tilt were compared using independent t tests. RESULTS:
      Compared with pitchers who did not demonstrate excessive contralateral trunk
      tilt, those with excessive contralateral trunk tilt pitched at a higher ball
      speed (mean, 32.6 +/- 2.2 vs 31.1 +/- 2.9 m/s, respectively; P = .019) and
      experienced a greater elbow proximal force (mean, 103.9 +/- 12.7 vs 93.2 +/- 13.9
      %weight, respectively; P = .001), shoulder proximal force (mean, 104.8 +/- 14.1
      vs 94.3 +/- 15.5 %weight, respectively; P = .004), elbow varus moment (mean, 4.29
      +/- 0.73 vs 3.84 +/- 0.8 %height*weight, respectively; P = .017), and shoulder
      internal rotation moment (mean, 4.21 +/- 0.71 vs 3.75 +/- 0.78 %height*weight,
      respectively; P = .011). Pitchers with excessive contralateral trunk tilt
      demonstrated less upper torso flexion at stride foot contact, less upper torso
      rotation, and greater upper torso contralateral flexion at maximal shoulder
      external rotation and ball release (P < .05). CONCLUSION: Excessive contralateral
      trunk tilt is a strategy that is associated with higher ball speeds and increased
      joint loading. CLINICAL RELEVANCE: Pitching with excessive contralateral trunk
      tilt, which can be identified through screening of the pitching technique, is
      associated with a benefit in performance and increased joint loading. Future
      study is warranted to determine if this strategy should be encouraged or
      discouraged by baseball coaches.

PMID- 23884306
TI  - Trunk and hip biomechanics influence anterior cruciate loading mechanisms in
      physically active participants.
AB  - BACKGROUND: Excessive trunk motion and deficits in neuromuscular control (NMC) of
      the lumbopelvic hip complex are risk factors for anterior cruciate ligament (ACL)
      injury. However, the relationship between trunk motion, NMC of the lumbopelvic
      hip complex, and triplanar knee loads during a sidestep cutting task has not been
      examined. PURPOSE: To determine if there is an association between multiplanar
      trunk motion, NMC of the lumbopelvic hip complex, and triplanar knee loads with
      ACL injury during a sidestep cutting task. STUDY DESIGN: Descriptive laboratory
      study. METHODS: The hip and knee biomechanics and trunk motion of 30 participants
      (15 male, 15 female) were analyzed during a sidestep cutting task using an
      optoelectric camera system interfaced to a force plate. Trunk and lower extremity
      biomechanics were calculated from the kinematic and ground-reaction force data
      during the first 50% of the stance time during the cutting task. Pearson product
      moment correlation coefficients were calculated between trunk and lower extremity
      biomechanics. Multiple linear regression analyses were carried out to determine
      the amount of variance in triplanar knee loading explained by trunk motion and
      hip moments. RESULTS: A greater internal knee varus moment (mean, 0.11 +/- 0.12
      N.m/kg*m) was associated with less transverse-plane trunk rotation away from the
      stance limb (mean, 20.25 degrees  +/- 4.42 degrees ; r = -0.46, P = .011) and a
      greater internal hip adduction moment (mean, 0.33 +/- 0.25 N.m/kg*m; r = 0.83, P
      < .05). A greater internal knee external rotation moment (mean, 0.11 +/- 0.08
      N.m/kg*m) was associated with a greater forward trunk flexion (mean, 7.62 degrees
      +/- 5.28 degrees ; r = 0.42, P = .020) and a greater hip internal rotation
      moment (mean, 0.15 +/- 0.16 N.m/kg*m; r = 0.59, P = .001). Trunk rotation and hip
      adduction moment explained 81% (P < .05) of the variance in knee varus moment.
      Trunk flexion and hip internal rotation moment explained 48% (P < .05) of the
      variance in knee external rotation moment. CONCLUSION: Limited trunk rotation
      displacement toward the new direction of travel and hip adduction moment are
      associated with an increased internal knee varus moment, while a combined
      increase in trunk flexion displacement and hip internal rotation moment is
      associated with a higher internal knee external rotation moment. CLINICAL
      RELEVANCE: Prevention interventions for ACL injury should encourage trunk
      rotation toward the new direction of travel and limit excessive trunk flexion
      while adjusting frontal- and transverse-plane hip NMC.

PMID- 23884307
TI  - Study of urological devices coated with fullerene-like nanoparticles.
AB  - Insertion of endoscopes and other medical devices into the human body are
      ubiquitous, especially among aged males. The applied force for the
      insertion/extraction of the device from the urethra must overcome endoscope
      surface-human-tissue interactions. In daily practice a gel is applied on the
      endoscope surface, in order to facilitate its entry into the urethra, providing
      also for local anesthesia. In the present work, a new solid-state lubricant has
      been added to the gel, in order to reduce the metal-urethra interaction and
      alleviate the potential damage to the epithelial tissue. For that purpose, a
      urethra model was designed and fabricated, which allowed a quantitative
      assessment of the applied force for extraction of the endoscope from a soft
      polymer-based ring. It is shown that the addition of MoS2 nanoparticles with
      fullerene-like structure (IF-MoS2) and in particular rhenium-doped nanoparticles
      (Re:IF-MoS2) to Esracain gel applied on the metal-lead reduced the friction
      substantially. The Re:IF-MoS2 showed better results than the undoped fullerene
      like nanoparticles and both performed better than the gel alone. The mechanism of
      friction reduction is attributed to fullerenes' ability to roll and act as a
      separator between the active parts of the model. 

PMID- 23884308
TI  - The patient perspective quantified.

PMID- 23884309
TI  - Measuring the patient's perspective.

PMID- 23884311
TI  - AKT1 gene mutation levels are correlated with the type of dermatologic lesions in
      patients with Proteus syndrome.

PMID- 23884312
TI  - Reduced inflammatory threshold indicates skin barrier defect in transglutaminase
      3 knockout mice.
AB  - Recently, a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed
      impaired hair development, but no gross defects in the epidermal barrier,
      although increased fragility of isolated corneocytes was demonstrated. Here we
      investigated the functionality of skin barrier in vivo by percutaneous
      sensitization to FITC in TGM3/KO (n=64) and C57BL/6 wild-type (WT) mice (n=36).
      Cutaneous inflammation was evaluated by mouse ear swelling test (MEST),
      histology, serum IgE levels, and by flow cytometry from draining lymph nodes.
      Inflammation-induced significant MEST difference (P<0.0001) was detected between
      KO and WT mice and was supported also by histopathology. A significant increase
      of CD4+ CD25+-activated T cells (P<0.01) and elevated serum IgE levels (P<0.05)
      in KO mice indicated more the development of FITC sensitization than an
      irritative reaction. Propionibacter acnes-induced intracutaneous inflammation
      showed no difference (P=0.2254) between the reactivity of WT and KO immune
      system. As in vivo tracer, FITC penetration from skin surface followed by two
      photon microscopy demonstrated a more invasive percutaneous penetration in KO
      mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier
      function and higher susceptibility to FITC sensitization indicating that TGM3 has
      a significant contribution to the functionally intact cutaneous barrier. 

PMID- 23884313
TI  - MicroRNA-203 regulates melanosome transport and tyrosinase expression in melanoma
      cells by targeting kinesin superfamily protein 5b.
AB  - MicroRNA (miR)-203 is known to be downregulated and to act as an anti-oncomir in
      melanoma cells. At present, we found that exogenous miR-203 increased
      pigmentation and protein expression levels of the melanoma antigen recognized by
      T cells (Melan-As/MART1s) and/or tyrosinase (TYR) in the human melanoma cells
      tested. Inversely, treatment with an inhibitor of miR-203 downregulated the
      expression level of TYR. The target gene of miR-203 involved in the mechanism was
      kinesin superfamily protein 5b (kif5b), which was revealed by gene silencing
      using short interfering RNA and luciferase activity assay. Furthermore,
      immunocytochemistry showed obvious accumulation of melanosomes around nuclei of
      human melanoma Mewo cells transfected with miR-203 or siR-kif5b. Importantly,
      treatment with the miR-203 inhibitor, but not miR-203, exhibited effects on human
      epidermal melanocytes isolated from lightly pigmented adult skin similar to those
      on melanoma cells. In addition, the data indicated that exogenous miR-203 also
      negatively regulated the cAMP response element-binding protein 1
      (CREB1)/microphthalmia-associated transcription factor (MITF)/Rab27a pathway,
      which is one of the main pathways active in melanoma cells. In conclusion, our
      data indicated that anti-oncogenic miR-203 had a pivotal role in melanoma through
      reducing melanosome transport and promoting melanogenesis by targeting kif5b and
      through negative regulation of the CREB1/MITF/Rab27a pathway. 

PMID- 23884314
TI  - Downregulation of SAMHD1 expression correlates with promoter DNA methylation in
      Sezary syndrome patients.

PMID- 23884315
TI  - Propionibacterium acnes Induces IL-1beta secretion via the NLRP3 inflammasome in
      human monocytes.
AB  - Propionibacterium acnes induction of inflammatory responses is a major
      etiological factor contributing to the pathogenesis of acne vulgaris. In
      particular, the IL-1 family of cytokines has a critical role in both initiation
      of acne lesions and in the inflammatory response in acne. In this study, we
      demonstrated that human monocytes respond to P. acnes and secrete mature IL-1beta
      partially via the NLRP3-mediated pathway. When monocytes were stimulated with
      live P. acnes, caspase-1 and caspase-5 gene expression was upregulated; however,
      IL-1beta secretion required only caspase-1 activity. P. acnes induced key
      inflammasome genes including NLRP1 and NLPR3. Moreover, silencing of NLRP3, but
      not NLRP1, expression by small interfering RNA attenuated P. acnes-induced IL
      1beta secretion. The mechanism of P. acnes-induced NLRP3 activation and
      subsequent IL-1beta secretion was found to involve potassium efflux. Finally, in
      acne lesions, mature caspase-1 and NLRP3 were detected around the pilosebaceous
      follicles and colocalized with tissue macrophages. Taken together, our results
      indicate that P. acnes triggers a key inflammatory mediator, IL-1beta, via NLRP3
      and caspase-1 activation, suggesting a role for inflammasome-mediated
      inflammation in acne pathogenesis. 

PMID- 23884316
TI  - Long-term survival of type XVII collagen revertant cells in an animal model of
      revertant cell therapy.

PMID- 23884317
TI  - Development and preliminary randomized controlled trial of a distress tolerance
      treatment for smokers with a history of early lapse.
AB  - INTRODUCTION: An inability to tolerate distress is a significant predictor of
      early smoking lapse following a cessation attempt. We conducted a preliminary
      randomized controlled trial to compare a distress tolerance (DT) treatment that
      incorporated elements of exposure-based therapies and Acceptance and Commitment
      Therapy to standard smoking cessation treatment (ST). METHODS: Smokers with a
      history of early lapse in prior quit attempts received either DT (N = 27; 9 2-hr
      group and 6 50-min individual sessions) or ST (N = 22; 6 90-min group and 1 20
      min individual session), plus 8 weeks of transdermal nicotine patch. RESULTS: At
      the end of behavioral treatment, odds of abstinence among participants receiving
      DT were 6.46 times greater than among participants receiving ST (66.7% vs.
      31.8%), equivalent to a medium- to large-effect size. Odds of abstinence for DT
      were still 1.73 times greater at 8 weeks, corresponding to a small- to medium
      effect size, although neither this difference nor those at 13 and 26 weeks were
      statistically significant. Furthermore, of those who lapsed to smoking during the
      first week postquit, DT participants had more than 4 times greater odds of
      abstinence than ST participants at the end of treatment. Relative to ST, DT
      participants also reported a larger decrease in experiential avoidance, a
      hypothesized DT treatment mediator, prior to quit day. The trajectory of negative
      mood and withdrawal symptoms in DT differed from ST and was largely consistent
      with hypotheses. CONCLUSIONS: Reasons for the decrease in abstinence in DT after
      treatment discontinuation and suggestions for future research are discussed.

PMID- 23884318
TI  - Just blowing smoke? Social desirability and reporting of intentions to quit
      smoking.
AB  - INTRODUCTION: Do cigarette smokers really want to quit smoking or do they simply
      say they do in order to placate others and avoid criticism? In surveys of
      smokers, stated quit intentions and reports of quit attempts may be biased by
      social desirability concerns. This makes it difficult to interpret large-scale
      state and national surveys of smoking behavior that collect data through
      telephone and face-to-face interviews, methods that tend to evoke high levels of
      socially desirable responding. METHODS: The 2007 Health Information National
      Trends Survey used a dual-frame design to query smokers' quit intentions and past
      quit attempts in 1 of 2 ways: A self-administered mail survey (low pressure for
      socially desirable responding; n = 563), or an interviewer-administered telephone
      survey (high pressure for socially desirable responding; n = 499). Estimates
      derived from the 2 formats were compared to test for social desirability effects.
      RESULTS: In both survey modes, approximately two thirds of smokers reported
      seriously considering quitting in the next 6 months (mail: 64.9%; telephone:
      68.9%), and approximately half reported making a quit attempt in the past year
      (mail: 54.9%; telephone: 52.3%). Neither difference approached significance in
      logistic regressions controlling for demographics (ps > .24). CONCLUSIONS: It
      appears that a large proportion of smokers in the United States aspire to live
      smoke-free lives and are not simply responding in a socially desirable manner to
      deflect criticism in an antismoking social climate. Future research should (1)
      replicate this study with greater statistical power, (2) examine the possible
      effects of survey context (e.g., health survey vs. smoking pleasure survey), and
      (3) explore survey mode effects in specific subpopulations.

PMID- 23884320
TI  - Prevalence and predictors of water pipe and cigarette smoking among secondary
      school students in London.
AB  - INTRODUCTION: Water pipe tobacco smoking appears to be an increasing public
      health concern, with anecdotal reports of higher prevalence than cigarette
      smoking among young people in some high-income countries. We examined the
      prevalence and predictors of water pipe and cigarette smoking among students
      attending secondary schools in a deprived, ethnically diverse part of inner
      London. METHODS: We conducted a 96-item, validated smoking habits questionnaire
      with 2,399 students from Years 8, 10, and 12/13 from 15 secondary schools in
      Brent, northwest London. Multilevel logistic regression models were used to
      examine predictors of current and ever cigarette and water pipe smoking. RESULTS:
      Current water pipe smoking prevalence was more than double that of cigarette
      smoking prevalence (7.6% vs. 3.4%, p < .001). One in 4 students had tried water
      pipe compared with 1 in 6 who had tried cigarette smoking (24.0% vs. 15.8%, p <
      .001). Significant predictors of ever water pipe use include being in a higher
      age group, South Asian or Middle Eastern ethnicity, and personal, family, or
      friends tobacco use. Significant predictors of ever cigarette use include being
      in a higher age group, White ethnicity, and personal, family, or friends tobacco
      use. Students attending schools with more water pipe cafes within 0.5 miles were
      more likely to be current water pipe users (AOR = 2.43, 95% CI = 1.33-4.42).
      CONCLUSIONS: Water pipe smoking may be more prevalent than cigarette smoking
      among young people in some high-income countries. Improved surveillance and
      dedicated tobacco control interventions are required to better understand the
      epidemiology of water pipe use and address its growing use.

PMID- 23884319
TI  - Menthol cigarette and marijuana use among adolescents.
AB  - INTRODUCTION: Menthol cigarette and marijuana use among adolescents is high;
      however, little is known about dual use in this age. Thus, we examined these
      rates among 2 samples of adolescents in Connecticut. METHODS: Study 1 examined a
      school-wide survey assessing variables related to cigarettes and marijuana among
      high school students (N = 837 [13% smokers]), and Study 2 examined these factors
      using baseline data of high school-aged, treatment-seeking, daily cigarette
      smokers prior to quitting (N = 132). RESULTS: In Study 1, lifetime marijuana use
      among all adolescents was 33% and past 30-day marijuana use was 21%. Among
      cigarette smokers, 55% reported smoking menthol cigarettes, 84% reported lifetime
      marijuana use, and 66% reported past 30-day marijuana use. Multivariate-adjusted
      logistic regression models indicated that cigarette smokers, when compared with
      nonsmokers, had greater rates of lifetime (odds ratio [OR] = 10.91) and past 30
      day marijuana use (OR = 10.44). Among smokers, use of menthol cigarettes, when
      compared with use of nonmenthol cigarettes, was associated with greater lifetime
      (OR = 5.05) but not past 30-day marijuana use. In Study 2 with daily smokers, 59%
      of adolescents reported use of menthol cigarettes and 66% reported past 30-day
      marijuana use. Compared with nonmenthol cigarette smokers, menthol cigarette
      smokers were more likely to report past 30-day marijuana use (OR = 2.44).
      CONCLUSIONS: Cigarette smoking is associated with marijuana use, and among
      smokers, menthol cigarette smoking further increased the odds of marijuana use.
      More research on the dual use of marijuana and tobacco is needed to inform
      prevention and treatment of substance use.

PMID- 23884321
TI  - Levels of nicotine in dust from homes of smokeless tobacco users.
AB  - BACKGROUND: Smokeless tobacco products, such as chewing tobacco or moist snuff,
      contain many of the same constituents as tobacco smoke and are also known to
      cause cancer; however, little attention has been paid to indirect exposure of
      children to tobacco constituents via parental smokeless tobacco use. METHODS: As
      part of the California Childhood Leukemia Study, we collected dust samples from 6
      residences occupied by smokeless tobacco users, 6 residences occupied by active
      smokers, and 20 tobacco-free residences. Children's potential for exposure to
      tobacco constituents was assessed using nicotine concentrations in vacuum dust
      measured by gas chromatography-mass spectrometry. RESULTS: Median nicotine
      concentrations for residences with smokeless tobacco users were significantly
      greater than median nicotine concentrations for tobacco-free homes and similar to
      median nicotine concentrations in homes of active smokers. Using generalized
      estimating equations derived from a multivariable marginal model to adjust for a
      history of parental smoking, income, residence construction date, and mother's
      age and race/ethnicity, we found nicotine levels from homes of smokeless tobacco
      users to be 21-fold higher than nicotine levels from tobacco-free homes. Based on
      mass balance equations, we hypothesize that nicotine is transferred to floors in
      homes of smokeless tobacco users primarily as a constituent of tobacco that is
      spilled or expectorated. CONCLUSIONS: Based on our findings, we conclude that
      children living with smokeless tobacco users may be exposed to nicotine and other
      constituents of tobacco via contact with contaminated dust and household
      surfaces.

PMID- 23884322
TI  - Long-term efficacy of click city(r): tobacco: a school-based tobacco prevention
      program.
AB  - INTRODUCTION: Click City ((r)) : Tobacco is an innovative, computer-based tobacco
      prevention program designed to be implemented in 5th-grade classrooms with a
      booster in 6th grade. The program targets etiological mechanisms predictive of
      future willingness and intentions to use tobacco and initiation of tobacco use.
      Each component was empirically evaluated to assure that it changed its targeted
      mechanism. This paper describes long-term outcomes for students who participated
      in a randomized controlled efficacy trial of the program. METHODS: A total of 26
      middle schools were stratified and randomly assigned to the Click City ((r)) :
      Tobacco program or Usual Curriculum. The 47 elementary schools that fed into each
      middle school were assigned to the same condition as their respective middle
      school. In Click City ((r)) : Tobacco schools, 1,168 students from 24 elementary
      schools and 13 middle schools participated. In Usual Curriculum schools, 1,154
      students from 23 elementary schools and 13 middle schools participated. All
      participating students completed baseline, post-6th grade program, and 7th grade
      assessments. RESULTS: As compared to students in schools that continued with
      their usual curriculum, intentions and willingness to smoke increased less from
      baseline to 6th grade and from baseline to 7th grade, among students in schools
      that used the Click City ((r)) : Tobacco curriculum. Changes in mechanisms were
      also in the expected direction. The program was particularly efficacious for at
      risk students. CONCLUSIONS: Results provide evidence to support the long-term
      efficacy of Click City ((r)) : Tobacco. Program development, based on an
      empirical evaluation of each component, most likely played a role in the success
      of the program.

PMID- 23884323
TI  - Pharmacokinetic and pharmacodynamics studies of nicotine after oral
      administration in mice: effects of methoxsalen, a CYP2A5/6 inhibitor.
AB  - INTRODUCTION: The use of novel oral nicotine delivery devices and compositions
      for human consumption and for animal research studies has been increasing in the
      last several years. METHODS: Studies were undertaken to examine whether the
      systemic administration of methoxsalen, an inhibitor of human CYP2A6 and mouse
      CYP2A5, would modulate nicotine pharmacokinetics and pharmacological effects
      (antinociception in the tail-flick, and hot-plate tests, and hypothermia) in male
      ICR mouse after acute oral nicotine administration. RESULTS: Administration of
      intra peritoneal (ip) methoxsalen significantly increased nicotine's Cmax,
      prolonged the plasma half-life (fourfold decrease) of nicotine, and increased its
      area under the curve (AUC) compared with ip vehicle treatment. Methoxsalen
      pretreatment prolonged the duration of nicotine-induced antinociception and
      hypothermia (15mg/kg, po) for periods up to 6- and 24-hr postnicotine
      administration, respectively. Additionally, methoxsalen potentiated nicotine
      induced antinociception and hypothermia as evidenced by leftward shifts in
      nicotine's dose-response curve. Furthermore, this prolongation of nicotine's
      effects after methoxsalen was associated with a parallel prolongation of nicotine
      plasma levels in mice. These data strongly suggest that variation in the rates of
      nicotine metabolic inactivation substantially alter pharmacological effects of
      nicotine given orally. CONCLUSION: We have shown that the pharmacological effects
      of inhibiting nicotine's metabolism after oral administration in mice are
      profound. Our results suggest that inhibiting nicotine metabolism can be used to
      dramatically enhance nicotine's bioavailability and its resulting pharmacology,
      which further supports this inhibitory approach for clinical development of an
      oral nicotine replacement therapy.

PMID- 23884324
TI  - Ferroelectric polarization in nanocrystalline hydroxyapatite thin films on
      silicon.
AB  - Hydroxyapatite nanocrystals in natural form are a major component of bone--a
      known piezoelectric material. Synthetic hydroxyapatite is widely used in bone
      grafts and prosthetic pyroelectric coatings as it binds strongly with natural
      bone. Nanocrystalline synthetic hydroxyapatite films have recently been found to
      exhibit strong piezoelectricity and pyroelectricity. While a spontaneous
      polarization in hydroxyapatite has been predicted since 2005, the reversibility
      of this polarization (i.e. ferroelectricity) requires experimental evidence. Here
      we use piezoresponse force microscopy to demonstrate that nanocrystalline
      hydroxyapatite indeed exhibits ferroelectricity: a reversal of polarization under
      an electrical field. This finding will strengthen investigations on the role of
      electrical polarization in biomineralization and bone-density related diseases.
      As hydroxyapatite is one of the most common biocompatible materials, our findings
      will also stimulate systematic exploration of lead and rare-metal free
      ferroelectric devices for potential applications in areas as diverse as in vivo
      and ex vivo energy harvesting, biosensing and electronics.

PMID- 23884325
TI  - Tuning activity-based probe selectivity for serine proteases by on-resin 'click'
      construction of peptide diphenyl phosphonates.
AB  - Activity-based probes (ABPs) are powerful tools for functional proteomics
      studies. Their selectivity can be influenced by modification of a recognition
      element that interacts with pockets near the active site. For serine proteases
      there are a limited number of simple and efficient synthetic procedures for the
      development of selective probes. Here we describe a new synthetic route combining
      solid and solution phase chemistries to generate a small library of diphenyl
      phosphonate probes. Building blocks carrying a P1 recognition element and an
      electrophilic phosphonate warhead were prepared in solution and 'clicked' on
      resin onto a tripeptide. We show the ability to modulate the activity and
      selectivity of diphenyl phosphonate ABPs and demonstrate activity-dependent
      labeling of endogenous proteases within a tissue proteome. The herein described
      synthetic approach therefore serves as a valuable method for rapid
      diversification of serine protease ABPs. 

PMID- 23884326
TI  - Characterization of a nanogland for the autotransplantation of human pancreatic
      islets.
AB  - Despite the clinical success of pancreatic islet transplantation, graft function
      is frequently lost over time due to islet dispersion, lack of neovascularization,
      and loss of physiological architecture. To address these problems, islet
      encapsulation strategies including scaffolds and devices have been developed,
      which produced encouraging results in preclinical models. However, islet loss
      from such architectures could represent a significant limitation to clinical use.
      Here, we developed and characterized a novel islet encapsulation silicon device,
      the NanoGland, to overcome islet loss, while providing a physiological-like
      environment for long-term islet viability and revascularization. NanoGlands,
      microfabricated with a channel size ranging from 3.6 nm to 60 MUm, were
      mathematically modeled to predict the kinetics of the response of encapsulated
      islets to glucose stimuli, based on different channel sizes, and to rationally
      select membranes for further testing. The model was validated in vitro using
      static and perifusion testing, during which insulin secretion and functionality
      were demonstrated for over 30-days. In vitro testing also showed 70-83% enhanced
      islet retention as compared to porous scaffolds, here simulated through a 200 MUm
      channel membrane. Finally, evidence of in vivo viability of human islets
      subcutaneously transplanted within NanoGlands was shown in mice for over 120
      days. In this context, mouse endothelial cell infiltration suggesting
      neovascularization from the host were identified in the retrieved grafts. The
      NanoGland represents a novel, promising approach for the autotransplantation of
      human islets. 

PMID- 23884328
TI  - Prussian blue nanoparticles operate as a contrast agent for enhanced
      photoacoustic imaging.
AB  - Prussian blue nanoparticles were explored for the first time as an excellent
      contrast agent for enhancing photoacoustic tomography in vitro and in vivo due to
      their superior absorption efficiency of near-infrared laser pulses at a
      wavelength of 765 nm. 

PMID- 23884327
TI  - Angular correction and complications of proximal first metatarsal osteotomies for
      hallux valgus deformity.
AB  - PURPOSE: Proximal first metatarsal osteotomies are recommended for the surgical
      treatment of moderate to severe hallux valgus deformity. This study aimed to
      compare correction of intermetatarsal and hallux valgus angles and complications
      of proximal crescentic, Ludloff, proximal opening wedge, proximal closing wedge,
      proximal chevron and other proximal first metatarsal osteotomies. METHODS: A
      systematic search for the keywords "(bunion OR hallux) AND (proximal OR
      crescentic OR basilar OR opening OR closing OR shelf OR Ludloff) AND osteotomy"
      in the online databases MEDLINE, Embase, CINAHL, Cochrane Central Register of
      Controlled Trials and Cochrane Database of Systematic Reviews was performed.
      RESULTS: There was a mean correction of hallux valgus angle of 20.1 degrees 
      [confidence interval (CI) 18.7-21.4] and of intermetatarsal angle of 8.1 degrees 
      (CI 7.7-8.9). The overall complication rate reached 18.7 %. CONCLUSIONS: The
      results of this study reveal higher corrective power of proximal osteotomies
      compared to meta-analysis data on diaphyseal osteotomies.

PMID- 23884330
TI  - Squamous cell carcinoma of the tympanic membrane.

PMID- 23884329
TI  - Deafness induction in mice.
AB  - HYPOTHESIS: How to induce most efficiently severe sensorineural hearing loss in
      mice using a single coadministration of an aminoglycoside antibiotic and a loop
      diuretic? BACKGROUND: The coadministration of aminoglycosides and a loop diuretic
      has been widely used to induce hair cell and spiral ganglion cell loss in guinea
      pigs. However, the development of new treatment strategies against sensorineural
      hearing loss, such as tissue engineering techniques, requires the use of mouse
      models. Previous attempts to induce hearing loss in mice have rendered
      inconsistent results because of resistance to aminoglycoside-induced ototoxicity.
      Especially inner hair cells seem to be resistant to aminoglycoside-induced
      ototoxicity. METHODS: In the present study, we aim to optimize hearing loss in
      mice, using a single high-dose kanamycin (700 and 1,000 mg/kg) injection followed
      by a furosemide (100 mg/kg) administration. Although previous studies used
      intraperitoneal furosemide injections 30 minutes after kanamycin administration,
      we used intravenous furosemide injections administered within 5 minutes after
      kanamycin treatment. RESULTS: Auditory brain stem responses illustrated severe
      threshold shifts, and histologic analysis showed marked outer hair cell
      destruction as well as spiral ganglion cell loss. The present protocol results in
      more severe inner hair cell loss when compared with the results of previous
      researches. CONCLUSION: We conclude that severe sensorineural hearing loss can be
      induced in mice. Moreover, we found that this mouse model can be augmented via
      the use of rapid intravenous furosemide administrations to maximize inner hair
      cell loss.

PMID- 23884331
TI  - Surface modification of mammalian cells with stimuli-responsive polymers.
AB  - In order to introduce alternative functions into mammalian cells and control them
      under ambient conditions, poly(N-isopropyl acrylamide) (PNIPAM) was immobilized
      on the cell surface. Cellular aggregation could be regulated by temperature
      change. In addition, separation of PNIPAM-conjugated glycoproteins was
      successfully performed. 

PMID- 23884332
TI  - Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe
      Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial.
AB  - PURPOSE: Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3)
      polyunsaturated fatty acids (PUFAs) has been found to decrease the production of
      disease-relevant inflammatory mediators that are implicated in the pathogenesis
      of chronic dry eye. This study evaluated the effect of a supplement containing
      both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe
      keratoconjunctivitis sicca in postmenopausal patients. METHODS: This multicenter,
      double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes)
      with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or
      placebo for 6 months. Disease parameters, including Ocular Surface Disease Index,
      Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green
      staining, and topographic corneal smoothness indexes (surface asymmetry index and
      surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks.
      The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured
      in conjunctival impression cytologies. RESULTS: The Ocular Surface Disease Index
      score improved with supplementation and was significantly lower than placebo (21
      +/- 4 vs. 34 +/- 5) after 24 weeks (P = 0.05, n = 19 per group). The surface
      asymmetry index was significantly lower in supplement-treated subjects (0.37 +/-
      0.03, n = 15) than placebo (0.51 +/- 0.03, n = 16) at 24 weeks (P = 0.005).
      Placebo treatment also significantly increased HLA-DR intensity by 36% +/- 9% and
      CD11c by 34% +/- 7% when compared with supplement treatment (n = 19 per group, P
      = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear
      breakup time, or corneal or conjunctival staining. CONCLUSIONS: Supplemental GLA
      and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained
      corneal surface smoothness, and inhibited conjunctival dendritic cell maturation
      in patients with postmenopausal keratoconjunctivitis sicca.Clinical Trial
      Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.

PMID- 23884333
TI  - Unilateral Variant of Late-Onset Lattice Corneal Dystrophy With the Pro501Thr
      Mutation in the TGFBI Gene Without Deposits in the Unaffected Cornea Using
      Confocal Microscopy.
AB  - PURPOSE: To report a case of a unilateral variant of late-onset lattice corneal
      dystrophy (LCD) with the Pro501Thr mutation in the TGFBI gene with unilaterality
      confirmed by confocal microscopy. METHODS: Case report. A 58-year-old man
      presented with visual impairment in his left eye of 20-year duration. Clinical
      examinations, molecular genetic analysis, and laser confocal microscopic analysis
      were performed. RESULTS: The slit-lamp examination showed thick branching lattice
      lines in the left corneal stroma with radial orientation. The right eye was
      asymptomatic and appeared normal without deposition or opacification. Laser
      confocal microscopy showed that highly reflective deposits or lattice-shaped
      materials in the left cornea were not present in the right cornea, confirming the
      complete unilaterality of this disease. Molecular genetic analysis confirmed the
      Pro501Thr mutation in the TGFBI gene previously associated with LCD type IIIA. No
      other mutations were found in this gene. No mutations in the lactoferrin gene
      previously associated with secondary amyloidosis were identified. CONCLUSIONS:
      The authors present a unilateral variant of late-onset LCD with a heterozygous
      Pro501Thr mutation in the TGFBI gene. No corneal deposits seen in the affected
      cornea were found in the unaffected cornea even by laser confocal microscopic
      analysis.

PMID- 23884335
TI  - Gallstone pancreatitis: why not cholecystectomy?

PMID- 23884336
TI  - The kallikreins: old proteases with new clinical potentials.

PMID- 23884334
TI  - The genomic basis of vomeronasal-mediated behaviour.
AB  - The vomeronasal organ (VNO) is a chemosensory subsystem found in the nose of most
      mammals. It is principally tasked with detecting pheromones and other chemical
      signals that initiate innate behavioural responses. The VNO expresses subfamilies
      of vomeronasal receptors (VRs) in a cell-specific manner: each sensory neuron
      expresses just one or two receptors and silences all the other receptor genes. VR
      genes vary greatly in number within mammalian genomes, from no functional genes
      in some primates to many hundreds in rodents. They bind semiochemicals, some of
      which are also encoded in gene families that are coexpanded in species with
      correspondingly large VR repertoires. Protein and peptide cues that activate the
      VNO tend to be expressed in exocrine tissues in sexually dimorphic, and sometimes
      individually variable, patterns. Few chemical ligand-VR-behaviour relationships
      have been fully elucidated to date, largely due to technical difficulties in
      working with large, homologous gene families with high sequence identity.
      However, analysis of mouse lines with mutations in genes involved in ligand-VR
      signal transduction has revealed that the VNO mediates a range of social
      behaviours, including male-male and maternal aggression, sexual attraction,
      lordosis, and selective pregnancy termination, as well as interspecific responses
      such as avoidance and defensive behaviours. The unusual logic of VR expression
      now offers an opportunity to map the specific neural circuits that drive these
      behaviours. 

PMID- 23884337
TI  - Cycle stability of the electrochemical capacitors patterned with vertically
      aligned carbon nanotubes in an LiPF6-based electrolyte.
AB  - The miniature ultracapacitors, with interdigitated electrodes of vertically
      aligned carbon nanotubes (VACNTs) and an inter-electrode gap of 20 MUm, have been
      prepared in the LiPF6 organic electrolyte with and without PVdF-HFP gel. PVdF-HFP
      between two opposing electrodes enhances the device reliability, but lessens its
      power performance because of the extra diffusion resistance. Also noteworthy are
      the gel influences on the cycle stability. When the applied voltage is 2.0 or 2.5
      V, both the LiPF6 and the gel capacitors exhibit excellent stability, typified by
      a retention ratio of >=95% after 10,000 cycles. Their coulombic efficiencies
      quickly rise up, and hold steady at 100%. Nonetheless, when the applied voltage
      is 3.5 or 4.0 V, the cycle stability deteriorates, since the negative electrode
      potential descends below 0.9 V (vs. Li), leading to electrolyte decomposition and
      SEI formation. For the LiPF6 capacitor, its retention ratio could be around 60%
      after 10,000 cycles and the coulombic efficiency of 100% is difficult to reach
      throughout its cycle life. On the other hand, the gel capacitor cycles energy
      with a much higher retention ratio, >80% after 10,000 cycles, and a better
      coulombic efficiency, even though electrolyte decomposition still occurs. We
      attribute the superior stability of the gel capacitor to its extra diffusion
      resistance which slows down the performance deterioration.

PMID- 23884338
TI  - The heat-shock protein-70-induced renoprotective effect is partially mediated by
      CD4+ CD25+ Foxp3 + regulatory T cells in ischemia/reperfusion-induced acute
      kidney injury.
AB  - Recent reports suggest the presence of heat-shock protein (HSP)-reactive T cells
      with a regulatory phenotype in various inflammatory diseases. To test whether HSP
      exerts renoprotective effects through regulatory T cells (Tregs),
      ischemia/reperfusion injury was done with or without heat preconditioning in
      mice. Splenocytes from heat-preconditioned mice had Treg expansion and a reduced
      proliferative response upon mitogenic stimulus. T cells from heat-preconditioned
      mice failed to reconstitute postischemic injury when adoptively transferred to T
      cell-deficient nu/nu mice in contrast to those from control mice. Tregs were also
      increased in heat-preconditioned ischemic kidneys. Depleting Tregs before heat
      preconditioning abolished the renoprotective effect, while adoptive transfer of
      these cells back into Treg-depleted mice partially restored the beneficial effect
      of heat preconditioning. Inhibition of HSP70 by quercetin suppressed Treg
      expansion, as well as renoprotective effects. Transferring Tregs in quercetin
      treated heat-preconditioned mice partially restored the beneficial effect of heat
      preconditioning. The specificity of immune cell HSP70 in renoprotection was
      confirmed by partial restoration of kidney injury when T cells from HSP70
      deficient heat preconditioned mice were adoptively transferred to nu/nu mice.
      Thus, the renoprotective effect of HSP70 may be partially mediated by a direct
      immunomodulatory effect through Tregs. Better understanding of immunomodulatory
      mechanisms of various stress proteins might facilitate discovery of new
      preventive strategies in acute kidney injury. 

PMID- 23884340
TI  - Extracellular volume expansion, measured by multifrequency bioimpedance, does not
      help preserve residual renal function in peritoneal dialysis patients.
AB  - Residual renal function is a major survival determinant for peritoneal dialysis
      patients. Hypovolemia can cause acute kidney injury and loss of residual renal
      function, and it has been suggested that patients receiving peritoneal dialysis
      should preferably be maintained hypervolemic to preserve residual renal function.
      Here we determined whether hydration status predicted long-term changes in
      residual renal function. Changes in residual renal function and extracellular
      water (ECW) to total body water (TBW) measured by multifrequency bioimpedance in
      237 adult patients who had paired baseline and serial 12 monthly measurements
      were examined. Baseline hydration status (ECW/TBW) was not significantly
      associated with preservation of residual renal function, unlike baseline and
      follow-up mean arterial blood pressure. When the cohort was split into tertiles
      according to baseline hydration status, there was no significant correlation seen
      between change in hydration status and subsequent loss in residual renal
      function. Increased ECW/TBW in peritoneal dialysis patients was not associated
      with preservation of residual renal function. Similarly, increments and
      decrements in ECW/TBW were not associated with preservation or reduction in
      residual renal function. Thus, our study does not support the view that
      overhydration preserves residual renal function and such a policy risks the
      consequences of persistent hypervolemia. 

PMID- 23884341
TI  - XAFS in dilute magnetic semiconductors.
AB  - X-Ray absorption fine structure (XAFS) spectroscopy has experienced a rapid
      development in the last four decades and has proved to be a powerful structure
      characterization technique in the study of local environments in condensed
      matter. In this article, we first introduce the XAFS basic principles including
      theory, data analysis and experiment in some detail. Then we attempt to make a
      review on the applications of XAFS to the study of atomic and electronic
      structure in dilute magnetic semiconductor (DMS) systems. The power of XAFS in
      characterizing this interesting material system, such as determining the
      occupation sites and distribution of the dopants, detecting the presence of metal
      clusters or secondary phases, as well as identifying the defect types and dopant
      valence, will be illuminated by selected examples. This review should be of
      interest both to newcomers in the DMS field and to an interdisciplinary community
      of researchers working in synthesis, characterization and utilization of DMS
      materials. 

PMID- 23884339
TI  - Early chronic kidney disease-mineral bone disorder stimulates vascular
      calcification.
AB  - The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an
      extremely important complication of kidney diseases. Here we tested whether CKD
      MBD causes vascular calcification in early kidney failure by developing a mouse
      model of early CKD in a background of atherosclerosis-stimulated arterial
      calcification. CKD equivalent in glomerular filtration reduction to human CKD
      stage 2 stimulated early vascular calcification and inhibited the tissue
      expression of alpha-klotho (klotho) in the aorta. In addition, osteoblast
      transition in the aorta was stimulated by early CKD as shown by the expression of
      the critical transcription factor Runx2. The ligand associated with the klotho
      fibroblast growth factor receptor complex, FGF23, was found to be expressed in
      the vascular media of sham-operated mice. Its expression was decreased in early
      CKD. Increased circulating levels of the osteocyte-secreted proteins, FGF23, and
      sclerostin may have been related to increased circulating klotho levels. Finally,
      we observed low-turnover bone disease with a reduction in bone formation rates
      more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular
      risk factors, vascular calcification, increased circulating klotho, FGF23 and
      sclerostin levels, and low-turnover renal osteodystrophy, was established in
      early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular
      osteoblastic transition, increased osteocytic secreted proteins, and inhibited
      skeletal modeling producing the CKD-MBD. 

PMID- 23884342
TI  - Dopaminergic influences on emotional decision making in euthymic bipolar
      patients.
AB  - We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive
      effects in euthymic patients with bipolar disorder (BPD); however, the emergence
      of impulse-control disorders has been documented in Parkinson's disease (PD)
      after pramipexole treatment. Performance on reward-based tasks is altered in
      healthy subjects after a single dose of pramipexole, but its potential to induce
      abnormalities in BPD patients is unknown. We assessed reward-dependent decision
      making in euthymic BPD patients pre- and post 8 weeks of treatment with
      pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires
      subjects to choose among four card decks (two risky and two conservative) and is
      designed to promote learning to make advantageous (conservative) choices over
      time. Thirty-four BPD patients completed both assessments (18 placebo and 16
      pramipexole). Baseline performance did not differ by treatment group (F=0.63;
      p=0.64); however, at week 8, BPD patients on pramipexole demonstrated a
      significantly greater tendency to make increasingly high-risk, high-reward
      choices across the five blocks, whereas the placebo group's pattern was similar
      to that reported in healthy individuals (treatment * time * block interaction,
      p<0.05). Analyses of choice strategy using the expectancy valence model revealed
      that after 8 weeks on pramipexole, BPD patients attended more readily to feedback
      related to gains than to losses, which could explain the impaired learning. There
      were no significant changes in mood symptoms over the 8 weeks, and no increased
      propensity toward manic-like behaviors were reported. Our results suggest that
      the enhancement of dopaminergic activity influences risk-associated decision
      making performance in euthymic BPD. The clinical implications remain unknown. 

PMID- 23884343
TI  - Asymmetrical synaptic cooperation between cortical and thalamic inputs to the
      amygdale.
AB  - Fear conditioning, a form of associative learning is thought to involve the
      induction of an associative long-term potentiation of cortical and thalamic
      inputs to the lateral amygdala. Here, we show that stimulation of the thalamic
      input can reinforce a transient form of plasticity (E-LTP) induced by weak
      stimulation of the cortical inputs. This synaptic cooperation occurs within a
      time window of 30 min, suggesting that synaptic integration at amygdala synapses
      can occur within large time windows. Interestingly, we found that synaptic
      cooperation is not symmetrical. Reinforcement of a thalamic E-LTP by subsequent
      cortical stimulation is only observed within a shorter time window. We found that
      activation of endocannabinoid CB1 receptors is involved in the time restriction
      of thalamic and cortical synaptic cooperation in an activity-dependent manner.
      Our results support the hypothesis that synaptic cooperation can underlie
      associative learning and that synaptic tagging and capture is a general mechanism
      in synaptic plasticity. 

PMID- 23884344
TI  - Investigation of hepatitis E outbreak among refugees - Upper Nile, South Sudan,
      2012-2013.
AB  - During the week of July 2, 2012, the deaths of two pregnant women and one child
      were reported by household mortality surveillance in Jamam refugee camp, Maban
      County, Upper Nile State, South Sudan. All were reported to have yellow eyes
      before death. During July 27-August 3, 2012, three adult males with acute onset
      jaundice were admitted to the Medecins Sans Frontieres (MSF) hospital in Jamam
      camp; two died within 4 days of admission. The Republic of South Sudan Ministry
      of Health, United Nations High Commissioner for Refugees (UNHCR), CDC, and
      humanitarian organizations responded through enhanced case surveillance, a
      serosurvey investigation, and targeted prevention efforts. As of January 27,
      2013, a total of 5,080 acute jaundice syndrome (AJS) cases had been reported from
      all four Maban County refugee camps (Doro, Gendrassa, Jamam, and Yusuf Batil).
      Hepatitis E virus (HEV) infection was confirmed in a convenience sample of cases
      in each camp. A cross-sectional serosurvey conducted in Jamam camp in November
      2012 indicated that 54.3% of the population was susceptible to HEV infection.
      Across all camps, an AJS case-fatality rate (CFR) of 10.4% was observed among
      pregnant women. The outbreak response has focused on improving safe drinking
      water availability, improving sanitation and hygiene, conducting active case
      finding, and optimizing clinical care, especially among pregnant women.
      Sustaining these improvements, along with strengthening community outreach, is
      needed to improve outbreak control. Further investigation of the potential role
      for the newly developed HEV vaccine in outbreak control also is needed. 

PMID- 23884345
TI  - Hepatitis B vaccine birthdose practices in a country where hepatitis B is endemic
      - Laos, December 2011-February 2012.
AB  - Chronic hepatitis B virus (HBV) infection causes approximately 325,000 deaths
      from cirrhosis and liver cancer each year in the Western Pacific Region of the
      World Health Organization (WHO). With an estimated infection prevalence of >8%,
      HBV is considered highly endemic in Laos and is most commonly transmitted from
      mother to child during birth and early childhood. A hepatitis B vaccine birth
      dose (HepB-BD) is needed to prevent mother-to-child HBV transmission. To assess
      gaps in coverage and identify possible remedies for improvement of coverage,
      during the 3-month period December 2011-February 2012, the Laos Ministry of
      Health and WHO staff members surveyed 37 health facilities in five provinces in
      Laos, inquiring about HepB-BD knowledge and practices among health-care providers
      and estimating HepB-BD coverage provided by the facilities. For facility-based
      births, the median HepB-BD coverage was 74% (interquartile range: 39%-97%).
      Hepatitis B vaccine was not in stock at 18 (49%) of the 37 facilities on the day
      they were visited. Of the 37 facilities, 17 (46%) assisted with home births, and
      23 (62%) conducted postnatal home visits. Of the 17 facilities that assisted with
      home births, seven (41%) included HepB-BD vaccination as part of the service; of
      the 23 that conducted postnatal home visits, 15 (65%) provided HepB-BD as part of
      the visit. However, among those reporting that they provided these outreach
      services, only 48 births were recorded as attended, and only 81 postnatal visits
      were recorded as conducted during the 3-month period. Health facilities can help
      prevent mother-to-child HBV transmission in Laos by ensuring vaccine
      availability, vaccinating all infants born in the facility, and enhancing
      outreach services for home births. 

PMID- 23884346
TI  - Human papillomavirus vaccination coverage among adolescent girls, 2007-2012, and
      postlicensure vaccine safety monitoring, 2006-2013 - United States.
AB  - Since mid-2006, the Advisory Committee on Immunization Practices (ACIP) has
      recommended routine vaccination of adolescent girls at ages 11 or 12 years with 3
      doses of human papillomavirus (HPV) vaccine. Two HPV vaccines are currently
      available in the United States. Both the quadrivalent (HPV4) and bivalent (HPV2)
      vaccines protect against HPV types 16 and 18, which cause 70% of cervical cancers
      and the majority of other HPV-associated cancers; HPV4 also protects against HPV
      types 6 and 11, which cause 90% of genital warts.* This report summarizes
      national HPV vaccination coverage levels among adolescent girls aged 13-17 years?
      from the 2007-2012 National Immunization Survey-Teen (NIS-Teen) and national
      postlicensure vaccine safety monitoring. Although vaccination coverage with >=1
      dose of any HPV vaccine increased from 25.1% in 2007 to 53.0% in 2011, coverage
      in 2012 (53.8%) was similar to 2011. If HPV vaccine had been administered during
      health-care visits when another vaccine was administered, vaccination coverage
      for >=1 dose could have reached 92.6%. Safety monitoring data continue to
      indicate that HPV4 is safe. Despite availability of safe and effective vaccines
      and ample opportunities for vaccine delivery in the health-care setting, HPV
      vaccination coverage among adolescent girls failed to increase from 2011 to 2012.

PMID- 23884349
TI  - RDoC and DSM-5: what's the fuss?

PMID- 23884348
TI  - Neurocognitive functioning of individuals with schizophrenia: using and not using
      drugs.
AB  - OBJECTIVES: Research on neurocognition in schizophrenia, using modest samples and
      self-rated assessments, reports drug use contributes to improved rather than
      impaired cognitive function. We have sought to replicate these findings in a
      large sample of patients that had their drug-use status confirmed by laboratory
      assays and evaluated the potential differences in cognitive function between
      patients with positive and negative results. METHODS: Nine hundred and seventy
      four schizophrenia patients completed neuropsychological and laboratory tests at
      screening/baseline of the Clinical Antipsychotic Trials of Intervention
      Effectiveness study. Radioimmunoassay (RIA) of hair tested for cannabis, cocaine
      and methamphetamine. RESULTS: Many patients screened positive for drug use (n =
      262; 27%), and there were no differences between patients with positive and
      negative results in terms of cognitive function after adjusting for multiple
      inference testing, except patients with positive RIA for methamphetamine
      demonstrated increased processing speed (corrected, P = .024). Moderator models
      were employed to explore potential subgroup differences in this pattern of
      results. At low medication dosages, patients with positive RIA for cocaine
      demonstrated decreased processing speed compared with patients with negative RIA
      for cocaine (uncorrected, P = .008). And for any other drugs with low
      psychopathology, patients with positive RIA demonstrated decreased working memory
      compared with patients with negative RIA (uncorrected, P = .006). CONCLUSIONS: No
      positive effects of cannabis on cognitive function were observed, and drug use
      was not associated with improved neurocognition across most of the subgroup
      characteristics explored in this sample of schizophrenia patients.

PMID- 23884351
TI  - Will brain cells derived from induced pluripotent stem cells or directly
      converted from somatic cells (iNs) be useful for schizophrenia research?
AB  - The reprogramming of nonneuronal somatic cells to induced pluripotent stem cells
      and their derivation to functional brain cells as well as the related methods for
      direct conversion of somatic cells to neurons have opened up the possibility of
      conducting research on cellular disease models from living schizophrenia
      patients. We review the published literature on schizophrenia that has used this
      rapidly developing technology, highlighting the need for specific aims and
      reproducibility. The key issues for consideration for future schizophrenia
      research in this field are discussed and potential investigations using this
      technology are put forward for critical assessment by the reader. 

PMID- 23884352
TI  - Interpretation of the coronary artery calcium score in combination with
      conventional cardiovascular risk factors: the Multi-Ethnic Study of
      Atherosclerosis (MESA).
AB  - BACKGROUND: The coronary artery calcium (CAC) score predicts coronary heart
      disease (CHD) events, but methods for interpreting the score in combination with
      conventional CHD risk factors have not been established. METHODS AND RESULTS: We
      analyzed CAC scores and CHD risk factor measurements from 6757 black, Chinese,
      Hispanic, and white men and women aged 45 to 84 years in the Multi-Ethnic Study
      of Atherosclerosis (MESA). CAC was associated with age, sex, race/ethnicity, and
      all conventional CHD risk factors. Multivariable models using these factors
      predicted the presence of CAC (C statistic=0.789) and degree of elevation (16% of
      variation explained) and can be used to update a "pretest" CHD risk estimate,
      such as the 10-year Framingham Risk Score, that is based on an individual's
      conventional risk factors. In scenarios in which a high CAC score is expected, a
      moderately elevated CAC score of 50 is reassuring (eg, reducing risk from 10% to
      6% in a healthy older white man), but when a low/zero CAC score is expected, even
      with identical pretest CHD risk, the same CAC score of 50 may be alarmingly high
      (eg, increasing risk from 10% to 20% in a middle-aged black woman with multiple
      risk factors). Both the magnitude and direction of the shift in risk varied
      markedly with pretest CHD risk and with the pattern of risk factors. CONCLUSIONS:
      Knowledge of what CAC score to expect for an individual patient, based on their
      conventional risk factors, may help clinicians decide when to order a CAC test
      and how to interpret the results.

PMID- 23884353
TI  - AMG145, a monoclonal antibody against proprotein convertase subtilisin kexin type
      9, significantly reduces lipoprotein(a) in hypercholesterolemic patients
      receiving statin therapy: an analysis from the LDL-C Assessment with Proprotein
      Convertase Subtilisin Kexin Type 9 Monoclonal Antibody Inhibition Combined with
      Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57 trial.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] is an emerging risk factor for cardiovascular
      disease. Currently, there are few available therapies to lower Lp(a). We sought
      to evaluate the impact of AMG145, a monoclonal antibody against proprotein
      convertase subtilisin kexin type 9 (PCSK9), on Lp(a). METHODS AND RESULTS: As
      part of the LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined
      With Statin Therapy (LAPLACE)-Thrombolysis in Myocardial Infarction (TIMI) 57
      trial, 631 patients with hypercholesterolemia receiving statin therapy were
      randomized to receive AMG145 at 1 of 3 different doses every 2 weeks or 1 of 3
      different doses every 4 weeks versus placebo. Lp(a) and other lipid parameters
      were measured at baseline and at week 12. Compared with placebo, AMG145 70 mg,
      105 mg, and 140 mg every 2 weeks reduced Lp(a) at 12 weeks by 18%, 32%, and 32%,
      respectively (P<0.001 for each dose versus placebo). Likewise, AMG145 280 mg, 350
      mg, and 420 mg every 4 weeks reduced Lp(a) by 18%, 23%, and 23%, respectively
      (P<0.001 for each dose versus placebo). The reduction in Lp(a) correlated with
      the reduction in low-density lipoprotein cholesterol (rho=0.33, P<0.001). The
      effect of AMG145 on Lp(a) was consistent regardless of age, sex, race, history of
      diabetes mellitus, and background statin regimen. Patients with higher levels of
      Lp(a) at baseline had larger absolute reductions but comparatively smaller
      percent reductions in Lp(a) with AMG145 compared with those with lower baseline
      Lp(a) values. CONCLUSIONS: AMG145 significantly reduces Lp(a), by up to 32%,
      among subjects with hypercholesterolemia receiving statin therapy, offering an
      additional, complementary benefit beyond robust low-density lipoprotein
      cholesterol reduction with regard to a patient's atherogenic lipid profile.

PMID- 23884354
TI  - Wintering waterbirds and recreationists in natural areas: a sociological approach
      to the awareness of bird disturbance.
AB  - Disturbance to wintering birds by human recreational activities has become a
      major concern for managers of many natural areas. Few studies have examined how
      recreationists perceive their effects on birds, although this impacts their
      behavior on natural areas. We surveyed 312 users on two coastal ornithological
      sites in Brittany, France, to investigate their perception of the effects of
      human activities on wintering birds. The results show that the awareness of
      environmental issues and knowledge of bird disturbance depends on the
      socioeconomic characteristics of each user group, both between the two sites and
      within each site. Results also indicate that, whatever the site and the user
      group, the vast majority of the respondents (77.6%) believed that their own
      presence had no adverse effects on the local bird population. Various arguments
      were put forward to justify the users' own harmlessness. Objective information on
      recreationists' awareness of environmental issues, and particularly on their own
      impact on birds, is important to guide managers in their choice of the most
      appropriate visitor educational programs. We recommend developing global but also
      specific educational information for each type of user to raise awareness of
      their own impact on birds.

PMID- 23884355
TI  - Changing human landscapes under a changing climate: considerations for climate
      assessments.
AB  - Climate change is a fundamental aspect of the Anthropocene. Climate assessments
      are frequently undertaken to evaluate climate change impacts, vulnerability, and
      adaptive capacity. Assessments are complex endeavors with numerous challenges.
      Five aspects of a climate assessment that can be particularly challenging are
      highlighted: choice of assessment strategy, incorporation of spatial linkages and
      interactions, the constraints of climate observations, interpretation of a
      climate projection ensemble, uncertainty associated with weather/climate
      dependency models, and consideration of landscape-climate influences. In
      addition, a climate assessment strategy that incorporates both traditional "top
      down" and "bottom-up" methods is proposed for assessments of adaptation options
      at the local/regional scale. Uncertainties associated with climate observations
      and projections and with weather/climate dependency (i.e., response) models are
      incorporated into the assessment through the "top-down" component, and
      stakeholder knowledge and experience are included through the "bottom-up"
      component. Considerable further research is required to improve assessment
      strategies and the usefulness and usability of assessment findings. In
      particular, new methods are needed which better incorporate spatial linkages and
      interactions, yet maintain the fine grain detail needed for decision making at
      the local and regional scales. Also, new methods are needed which go beyond
      sensitivity analyses of the relative contribution of land use and land cover
      changes on local/regional climate to more explicitly consider landscape-climate
      interactions in the context of uncertain future climates. Assessment teams must
      clearly communicate the choices made when designing an assessment and recognize
      the implications of these choices on the interpretation and application of the
      assessment findings. 

PMID- 23884356
TI  - Perceptions of wildfire and landscape change in the Kenai Peninsula, Alaska.
AB  - Despite a broad literature addressing the human dimensions of wildfire, current
      approaches often compartmentalize results according to disciplinary boundaries.
      Further, relatively few studies have focused on the public's evolving perceptions
      of wildfire as communities change over time. This paper responds to these gaps by
      exploring perceptions of landscape dynamics and wildfire between 2003 and 2007
      using a typological framework of intersecting ecological, social, and cultural
      processes. Designed as a restudy, and using key informant interviews, this
      research allowed us to observe risk perception as they are related to community
      challenges and opportunities in the Kenai Peninsula, Alaska. Risk perceptions
      were examined as an integral part of community and landscape change. Wildfire was
      a concern among informants in 2003 and remained a concern in 2007, although
      informants were less likely to discuss it as a major threat compared to the
      original study. Informants in the western part of the peninsula tended to express
      more concern about wildfire than their eastern counterparts largely due to their
      experiences with recent fires. Other important factors residents considered
      included changing forest fuels, the expanding wildland urban interface, and
      contrasting values of new residents. Underscoring the localized nature of risk
      perceptions, informants had difficulty describing the probability of a wildfire
      event in a geographical context broader than the community scale. This paper
      demonstrates how a holistic approach can help wildfire and natural resource
      professionals, community members, and other stakeholders understand the social
      and physical complexities influencing collective actions or inactions to address
      the threat of wildfire. 

PMID- 23884357
TI  - Combination of enzyme- and Lewis acid-catalyzed reactions: a new method for the
      synthesis of 6,7-dihydrobenzofuran-4(5H)-ones starting from 2,5-dimethylfuran and
      1,3-cyclohexanediones.
AB  - The Lewis acid-catalyzed domino 1,2-addition/1,4-addition/elimination between (Z)
      3-hexene-2,5-dione and 1,3-dicarbonyls delivers 3-methyl-6,7-dihydrobenzofuran
      4(5H)-ones exclusively with yields up to 82%. The combination of this new process
      with the laccase-catalyzed formation of (Z)-3-hexene-2,5-dione by oxidative
      cleavage of 2,5-dimethylfuran allows for the synthesis of 6,7-dihydrobenzofuran
      4(5H)-ones starting directly from 2,5-dimethylfuran. 

PMID- 23884358
TI  - Microfluidic integrated optoelectronic tweezers for single-cell preparation and
      analysis.
AB  - We report a novel microfluidic integrated optoelectronic tweezers (OET) platform
      for single-cell sample preparation and analysis. Integration of OET and
      microfluidics is achieved by embedding single-wall carbon nanotube (SWNT)
      electrodes into multilayer PDMS structures. This integrated platform allows users
      to selectively pick up individual cells from a population with light beams based
      on their optical signatures such as size, shape, and fluorescence, and transport
      them into isolated chambers using light induced dielectrophoretic forces.
      Isolated cells can be encapsulated into nanoliter liquid plugs and transported
      out of the platform for downstream molecule analysis using standard commercial
      instruments. 

PMID- 23884359
TI  - Facile preparation of durable and robust superhydrophobic textiles by dip coating
      in nanocomposite solution of organosilanes.
AB  - This article presents a facile approach for the preparation of durable and robust
      superhydrophobic textiles by simply dip coating in a nanocomposite solution of
      fluoro-free organosilanes. The superhydrophobic textiles exhibit good water
      repellency and excellent mechanical, chemical and environmental stability. 

PMID- 23884360
TI  - Femtosecond laser processing by using patterned vector optical fields.
AB  - We present and demonstrate an approach for femtosecond laser processing by using
      patterned vector optical fields (PVOFs) composed of multiple individual vector
      optical fields. The PVOFs can be flexibly engineered due to the diversity of
      individual vector optical fields in spatial arrangement and distribution of
      states of polarization, and it is easily created with the aid of a spatial light
      modulator. The focused PVOFs will certainly result in various interference
      patterns, which are then used to fabricate multi-microholes with various patterns
      on silicon. The present approach can be expanded to fabricate three-dimensional
      microstructures based on two-photon polymerization. 

PMID- 23884361
TI  - Identification of two novel multiple recombinant avian leukosis viruses in two
      different lines of layer chicken.
AB  - Avian leukosis virus (ALV) is the most common oncogenetic retrovirus that emerges
      spontaneously as a result of recombination between exogenous viruses, exogenous
      viruses and endogenous viruses, and exogenous viruses and non-homologous cellular
      genes. In the present study, two natural recombinant avian leukosis viruses
      (rALVs) (LC110515-5 and LC110803-5) carrying a subgroup C gp85 gene, a subgroup E
      gp37 gene, and a subgroup J 3'UTR and 3'LTR were isolated from two different
      lines of layer flocks, Black-bone silky fowl (BSF) and commercial layer chicken,
      that suffered from myeloid leukosis. Although tumours were not observed in rALV
      infected individual chickens, other non-neoplastic inflammatory lesions were
      evident. The two rALVs were cultured on DF-1 cells and identified by PCR,
      immunofluorescence assay and gene sequencing. The gp85 nucleotide sequence in the
      two isolates displayed a high identity (>95 %) with that of the gp85 gene in ALV
      C, but the identity was less than 90 % with ALV-A/B/D/E and only 51 % with ALV-J.
      Phylogenetic analysis of the nucleotide and amino acid sequences confirmed that
      the two isolates were recombinant between ALV-C, ALV-E and ALV-J. Subgroup C ALV
      is rarely found in field cases. This report is the first to provide evidence that
      ALV-C has recombined with ALV-E and ALV-J in two different chicken lines. The
      source and characteristics of the two rALVs and ALV-C need to be further
      investigated. 

PMID- 23884363
TI  - Dengue virus-infected human monocytes trigger late activation of caspase-1, which
      mediates pro-inflammatory IL-1beta secretion and pyroptosis.
AB  - Dengue virus (DENV) infection affects millions of people annually and has the
      potential to cause fatal haemorrhagic fever and shock. Although the underlying
      pathogenesis of severe dengue illness is still unclear, current evidence suggests
      that severe disease progression has an immunological basis. In this study, we
      investigated the role of caspase-1 during host-pathogen interactions within DENV
      infected human monocytes. Using DENV-infected primary monocytes, we examined
      caspase-1 at various levels of gene expression and probed for potential immune
      consequences mediated by caspase-1 such as secretion of pro-inflammatory IL-1beta
      and pyroptotic cell death. We report that DENV-infected monocytes upregulated
      functional caspase-1 mRNA and pro-caspase-1 activation as a late response to
      infection. In addition, we found that caspase-1 is responsible for IL-1beta
      secretion and pyroptosis of DENV-infected monocytes. Together, our results show
      that late caspase-1 activation within DENV-infected monocytes can contribute to
      pro-inflammatory outcomes that might play a role in dengue immunopathogenesis. 

PMID- 23884362
TI  - ROS upregulation during the early phase of retroviral infection plays an
      important role in viral establishment in the host cell.
AB  - Recent studies suggest that low levels of reactive oxygen species (ROS) often
      modulate normal intracellular signalling pathways, determine cell fates and
      control cell proliferation. We found that infection of astrocytes with the
      neuropathogenic retrovirus ts1, a mutant of Moloney murine leukemia retrovirus,
      upregulated ROS at low levels during the early phase of infection. This
      upregulation of intracellular ROS with downregulation of NADPH levels during the
      early phase of ts1 infection was a separate event from the upregulation of ROS
      during the late phase while ts1-mediated cell death occurred. The treatment of
      apocynin, a potential inhibitor of NADPH oxidase (NOX), inhibited establishment
      of the ts1 virus in the host cell. These results suggested that ROS generated as
      a consequence of the activation of NOX may play an important role in the early
      events of the virus life cycle leading to the establishment of the virus in the
      host cell. The in vitro results were further supported by an in vivo experiment
      which showed that the treatment of apocynin decreased viral titre in the ts1
      infected mouse brain and increased the lifespan of infected mice. This study
      provides the first in vitro and in vivo evidence on a mechanism for how ROS are
      involved in ts1 retrovirus infection and ts1-mediated neurodegenerative disease.
      Our findings focusing on the early phase of the ts1 retrovirus life cycle could
      provide a better understanding of retroviral life cycle, which may offer specific
      therapeutic targets for suppressing viral replication and alleviating
      neurodegenerative symptoms in a mouse model. 

PMID- 23884364
TI  - Antiviral activity of sulfated Chuanmingshen violaceum polysaccharide against
      Newcastle disease virus.
AB  - Newcastle disease virus (NDV) is a member of Paramyxovirinae subfamily and can
      infect most species of birds causing severe economic losses. The current control
      measure is vaccination, but infections cannot be completely prevented. It remains
      a constant threat to the poultry industry and new control measures are urgently
      needed. This study demonstrates that sulfated Chuanmingshen violaceum
      polysaccharides (sCVPSs) were potent inhibitors of NDV, with 50 % inhibitory
      concentrations (IC50) ranging from 62.55 to 76.31 ug ml(-1) in Baby hamster
      kidney fibroblasts clone 21 (BHK-21) and from 101.57 to 125.90 ug ml(-1) in
      chicken embryo fibroblasts (CEF). sCVPS is more effective than heparan sulfate
      (HS; as a positive control) with IC50 values of 99.28 ug ml(-1) in BHK-21 and
      118.79 ug ml(-1) in CEF. sCVPSs and HS exhibit anti-NDV activity by prevention of
      the early stages of viral life. The mechanism of action study indicated that
      virus adsorption in BHK-21, and both virus adsorption and penetration in CEF were
      inhibited by sCVPSs. When the number of viruses was increased to an m.o.i. of 0.1
      in the immunofluorescence study and to an m.o.i. of 1 in the fluorescent
      quantitative PCR study, viral infection was also significantly suppressed; the
      antiviral activity of sCVPSs was independent of the m.o.i. sCVPSs also prevented
      the cell-to-cell spread of NDV. In vivo tests carried out on specific pathogen
      free (SPF) chickens showed that sCVPSs also inhibited virus multiplication in
      heart, liver, spleen, lung and kidney. These results indicated that sCVPSs
      perform more effectively than HS as antiviral agents against NDV, and can be
      further examined for their potential as an alternative control measure for NDV
      infection. 

PMID- 23884365
TI  - Emerging novel porcine parvoviruses in Europe: origin, evolution, phylodynamics
      and phylogeography.
AB  - To elucidate the spatiotemporal phylodynamics, dispersion and evolutionary
      processes underlying the emergence of novel porcine parvovirus 2 (PPV2), PPV3 and
      PPV4 species, we analysed all available complete capsid genes, together with
      ours, obtained in Europe. Bayesian phylogeography indicates that Romania (PPV2
      and PPV4) and Croatia (PPV3) are the most likely ancestral areas from which PPVs
      have subsequently spread to other European countries and regions. The timescale
      of our reconstruction supported a relatively recent history of the currently
      circulating novel PPV species (1920s to 1980s) in the domestic or sylvatic host.
      While PPV2 strains exhibited a large genetic exchange characterized by
      significant recombination and gene flow between distinct regions and hosts, PPV3
      and PPV4 showed a diversification reflected by the accumulation of geographically
      structured polymorphisms. The RNA-like evolutionary rates detected inter- and
      intrahost recombination and the positive selection sites provided evidence that
      the PPV2-4 capsid gene plays a prominent role in host adaptation. 

PMID- 23884366
TI  - African, Amerindian and European hepatitis B virus strains circulate on the
      Caribbean Island of Martinique.
AB  - Ten Hepatitis B virus (HBV) genotypes, as well as numerous subgenotypes, have
      been described in well-characterized ethnogeographical populations. Martinique
      has been at a crossroads between Africa, Europe, India and the Americas because
      of the slave trade (17th-19th centuries), followed by an important immigration of
      Indian and West African workers. In this work, we aimed to study the molecular
      epidemiology of HBV infection in Martinique according to this unique settlement
      pattern. To that end, blood samples from 86 consecutive HBV-infected patients
      from the main hospitals of the island, were retrospectively analysed. Direct
      sequencing of the pre-S1 or pre-C-C region or complete genome sequencing,
      followed by phylogenetic analyses were performed. HBV genotypes were: HBV/A1
      (68.6 %), HBV/A2 (10.5 %), HBV/D, mainly HBV/D3 and HBV/D4 (8.1 %), HBV/F (3.5
      %), and also HBV/E (2.3 %), two strains isolated from two West-African patients.
      Moreover, 74 % of the HBeAg-negative strains harboured classical pre-C-C
      mutations, and most HBV/A1 strains also containing specific mutations. Finally,
      various patterns of deletion mutants in pre-S and pre-C-C regions were found. In
      conclusion, our findings point to historical and migration-related issues in HBV
      genotype distribution suggesting that HBV/A1, but not HBV/E, was imported from
      Africa during the slave trade, and further supporting the hypothesis that HBV/E
      has emerged recently in West Africa (<150 years). Potential origins of 'European'
      HBV/A2 and HBV/D3, 'Amerindian' HBV/F, and HBV/D4 strains are also discussed.
      Such HBV genetic diversity, beyond its epidemiological interest, may have a
      clinical impact on the natural history of HBV infection in Martinique. 

PMID- 23884367
TI  - Crystal structure of Junin virus nucleoprotein.
AB  - Junin virus (JUNV) has been identified as the aetiological agent of Argentine
      haemorrhagic fever (AHF), which is a serious public health problem with
      approximately 5 million people at risk. It is treated as a potential bioterrorism
      agent because of its rapid transmission by aerosols. JUNV is a negative-sense
      ssRNA virus that belongs to the genus Arenavirus within the family Arenaviridae,
      and its genomic RNA contains two segments encoding four proteins. Among these,
      the nucleoprotein (NP) has essential roles in viral RNA synthesis and immune
      suppression, but the molecular mechanisms of its actions are only partially
      understood. Here, we determined a 2.2 A crystal structure of the C-terminal
      domain of JUNV NP. This structure showed high similarity to the Lassa fever virus
      (LASV) NP C-terminal domain. However, both the structure and function of JUNV NP
      showed differences compared with LASV NP. This study extends our structural
      insight into the negative-sense ssRNA virus NPs. 

PMID- 23884369
TI  - Breast cancer stem cells--ready for their close-up?

PMID- 23884368
TI  - Pacemaking kisspeptin neurons.
AB  - Kisspeptin (Kiss1) neurons are vital for reproduction. Gonatotrophin-releasing
      hormone (GnRH) neurons express the kisspeptin receptor (GPR54), and kisspeptins
      potently stimulate the release of GnRH by depolarizing and inducing sustained
      action potential firing in GnRH neurons. As such, Kiss1 neurons may be the
      presynaptic pacemaker neurons in the hypothalamic circuitry that controls
      reproduction. There are at least two different populations of Kiss1 neurons; one
      in the rostral periventricular area (RP3V) that is stimulated by oestrogens and
      the other in the arcuate nucleus that is inhibited by oestrogens. How each of
      these Kiss1 neuronal populations participates in the regulation of the
      reproductive cycle is currently under intense investigation. Based on
      electrophysiological studies in the guinea-pig and mouse, Kiss1 neurons in
      general are capable of generating burst-firing behaviour. Essentially, all Kiss1
      neurons, which have been studied thus far in the arcuate nucleus, express the ion
      channels necessary for burst firing, which include hyperpolarization-activated,
      cyclic nucleotide-gated cation (HCN) channels and the T-type calcium (Cav3.1)
      channels. In voltage-clamp conditions, these channels produce distinct currents
      that can generate burst-firing behaviour in current-clamp conditions. The future
      challenge is to identify other key channels and synaptic inputs involved in the
      regulation of the firing properties of Kiss1 neurons and the physiological
      regulation of the expression of these channels and receptors by oestrogens and
      other hormones. The ultimate goal is to understand how Kiss1 neurons control the
      different phases of GnRH neurosecretion, hence reproduction. 

PMID- 23884371
TI  - Molecular interactions of different size AuNP-COOH nanoparticles with human
      fibrinogen.
AB  - Protein adsorption influences greatly the performance of materials used in
      biotechnology and biomedicine. The binding of fibrinogen (Fg) to nanoparticles
      (NPs) can result in protein unfolding and exposure of cryptic epitopes that
      subsequently interact with cell surface receptors. The response and its degree
      are dependent on the size, charge, and concentration of the NPs. In this study
      the binding kinetics of human Fg to negatively charged 11-mercaptoundecanoic acid
      functionalized gold nanoparticles (AuNPs-COOH) ranging from 5.6 to 64.5 nm were
      examined. The larger NPs bound Fg with a larger number of proteins per square
      unit and a higher dissociation rate (Kd'), but with decreased affinity. By
      contrast, the 5.6 nm AuNPs-COOH behaved in a cooperative manner for Fg
      adsorption. In the presence of excess Fg, only the 64.5 nm AuNPs-COOH showed
      severe aggregation, whose degree was alleviated in a dilute Fg solution. The Fg
      is adsorbed through a side-on configuration and both side-on and end-on
      configurations on the smaller (5.6 and 14.2 nm) and 31.5 nm AuNPs-COOH,
      respectively. It also retains the native conformation. By contrast, on the 64.5
      nm AuNPs-COOH the Fg adopts the end-on configuration and loses most of the
      secondary structure. 

PMID- 23884370
TI  - Reciprocal expression of the endocytic protein HIP1R and its repressor FOXP1
      predicts outcome in R-CHOP-treated diffuse large B-cell lymphoma patients.
AB  - We previously identified autoantibodies to the endocytic-associated protein
      Huntingtin-interacting protein 1-related (HIP1R) in diffuse large B-cell lymphoma
      (DLBCL) patients. HIP1R regulates internalization of cell surface receptors via
      endocytosis, a process relevant to many therapeutic strategies including CD20
      targeting with rituximab. In this study, we characterized HIP1R expression
      patterns, investigated a mechanism of transcriptional regulation and its clinical
      relevance in DLBCL patients treated with immunochemotherapy (rituximab,
      cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP). HIP1R was
      preferentially expressed in germinal center B-cell-like DLBCL (P<0.0001) and
      inversely correlated with the activated B-cell-like DLBCL (ABC-DLBCL) associated
      transcription factor, Forkhead box P1 (FOXP1). HIP1R was confirmed as a direct
      FOXP1 target gene in ABC-DLBCL by FOXP1-targeted silencing and chromatin
      immunoprecipitation. Lower HIP1R protein expression (<= 10% tumoral positivity)
      significantly correlated with inferior overall survival (OS, P=0.0003) and
      progression-free survival (PFS, P=0.0148) in R-CHOP-treated DLBCL patients
      (n=157). Reciprocal expression with >= 70% FOXP1 positivity defined
      FOXP1(hi)/HIP1R(lo) patients with particularly poor outcome (OS, P=0.0001; PFS,
      P=0.0016). In an independent R-CHOP-treated DLBCL (n=233) microarray data set,
      patients with transcript expression in lower quartile HIP1R and
      FOXP1(hi)/HIP1R(lo) subgroups exhibited worse OS, P=0.0044 and P=0.0004,
      respectively. HIP1R repression by FOXP1 is strongly associated with poor outcome,
      thus further understanding of FOXP1-HIP1R and/or endocytic signaling pathways
      might give rise to novel therapeutic options for DLBCL.

PMID- 23884372
TI  - Impairment of salivary mucin production resulting in declined salivary viscosity
      during naproxen administration as a potential link to upper alimentary tract
      mucosal injury.
AB  - OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) contribute to the
      esophageal mucosal injury through its direct topical impact on the luminal aspect
      of the surface epithelium. Its indirect, systemic impact, however, on salivary
      component of the esophageal pre-epithelial barrier remains to be explored.
      Therefore, salivary mucin secretion and viscosity at baseline and during naproxen
      placebo, as well as naproxen-rabeprazole, administration were investigated.
      METHODS: Twenty-one asymptomatic volunteers were included in this double-blind,
      placebo-controlled, crossover designed study. Salivary samples were obtained in
      basal and pentagastrin-stimulated conditions (6 mg/kg s.c.) mimicking the food
      stimulated conditions. Patients received 7 days of naproxen-placebo or naproxen
      rabeprazole with a 2-week washout period in between. Salivary mucin content and
      viscosity were measured before and after treatment using periodic acid/Schiff's
      methodology and Cone/Plate Digital Viscometer, respectively. RESULTS: The rate of
      salivary mucin secretion in basal condition declined by 32% during administration
      of naproxen-placebo (11.3+/-1.7 vs. 16.8+/-3.3 mg/h). Salivary mucin secretion in
      pentagastrin-stimulated condition declined significantly (by 34%) during the
      administration of naproxen-placebo (13.6+/-1.5 vs. 20.7+/-3.0 mg/h; P<0.05).
      Viscosity significantly decreased after naproxen-placebo administration in basal
      (by 60%) and stimulated conditions (by 56%) (P<0.001). Coadministration of
      rabeprazole at least partly restored the naproxen-induced decline of salivary
      mucin in basal condition (by 8%), and pentagastrin-stimulated conditions (by
      30%). CONCLUSIONS: A significant decline of salivary mucin and viscosity during
      administration of naproxen may at least partly explain a propensity of patients
      on chronic therapy with NSAIDs to the development of esophageal mucosal injury
      and complications. In addition the trend to restorative capacity of rabeprazole
      on the quantitative impairment of salivary mucin during administration of
      naproxen may potentially translate into its tangible clinical benefit but it
      requires further investigation.

PMID- 23884373
TI  - Urodynamic characterization of lower urinary tract symptoms in men less than 40
      years of age.
AB  - PURPOSE: Lower urinary tract symptoms (LUTS) in young men are becoming a more
      recognized urologic issue that can arise from many causes, each with their own
      management strategy. The purpose of this study was to determine the rates and
      types of voiding dysfunction causing LUTS in men under 40 years. METHODS:
      Videourodynamic studies (VUDS) of 87 men 40 years of age or less with LUTS for
      greater than 6 months, performed between July 2004 and June 2012 at Weill Cornell
      Medical College, were retrospectively analyzed. Patients with culture-proven
      bacterial prostatitis, symptoms for less than 6 months, a history of neurologic
      disease, or previous urological surgery affecting voiding function were excluded
      from the analysis. RESULTS: The mean age of the patients was 31.84 +/- 5.78.
      There were 37 patients that presented with more than one urinary symptom (42.5
      %). The most frequent complaints included: urinary frequency (N = 42, 48.28 %),
      difficulty with urination (N = 41, 47.13 %), and urinary urgency (N = 21, 24.14
      %). The most common urodynamic abnormality was bladder outlet obstruction (BOO)
      (N = 37, 42.53 %), dysfunctional voiding (N = 25, 28.74 %), detrusor
      underactivity (N = 10, 11.49 %), and detrusor overactivity (N = 7, 8.05 %). There
      were no differences seen in AUA symptom and quality of life scores across
      diagnosis groups. CONCLUSIONS: Lower urinary tract symptoms can present in
      younger men with a variety of types of voiding dysfunction. This study uses VUDS
      to show that the most common types of voiding dysfunction in this population with
      chronic LUTS are BOO followed by dysfunctional voiding.

PMID- 23884374
TI  - Phenylalanine-containing cyclic dipeptides--the lowest molecular weight
      hydrogelators based on unmodified proteinogenic amino acids.
AB  - Cyclic dipeptides (diketopiperazines - DKPs) that are based on the proteinogenic
      amino acid phenylalanine in combination with serine, cysteine, glutamate,
      histidine and lysine are described as simple and remarkable low molecular weight
      hydrogelators. Blends of selected DKPs show remarkable pH-dependent properties
      and can be applied as easy to tune materials in drug delivery. 

PMID- 23884376
TI  - Stabilization of Si(0) and Ge(0) compounds by different silylenes and germylenes:
      a density functional and molecular electrostatic study.
AB  - Recently, the chemistry of element (0) compounds has attracted the attention of
      both experimental and theoretical chemists. In this article, some new Si(0) and
      Ge(0) compounds stabilized by different silylene and germylene ligands are
      studied theoretically by applying quantum chemical calculations and topography
      mapping of molecular electrostatic potential (MESP). These compounds are found to
      have high donor-acceptor bond strengths and are thermodynamically stable. The
      nature of the molecular orbitals, negative values of MESP at its critical points,
      as well as proton affinity values suggest that they are very good nucleophiles.
      Calculated proton affinity values suggest the possible isolation of their
      diprotonated salts. 

PMID- 23884375
TI  - The tip of the iceberg. Incidence of disclosed cases of child sexual abuse in
      Switzerland: results from a nationwide agency survey.
AB  - OBJECTIVES: Child sexual abuse (CSA) is considered a major risk factor for a
      variety of health problems both in childhood and in later adult life. While
      population-based surveys aim to establish the real incidence rates of CSA by
      interviewing potential (past) victims, agency surveys focus on the rates of CSA
      reported to the authorities. METHODS: We conducted a nationwide agency survey of
      CSA in Switzerland. Data were collected from 350 agencies through an anonymous
      online form during a 6-month period. For data collection, we used a modified
      version of the case reporting form translated from the American National
      Incidence Study (NIS-4). RESULTS: About 2.68 cases of CSA per 1,000 children per
      year are disclosed to agencies (1.11 in males, 4.33 in females). This is roughly
      twice the average incidence rate reported in methodologically similar studies
      from Canada, the US, and Australia. CONCLUSIONS: In Switzerland, the majority of
      disclosed cases of CSA are handled by specialized yet semi-public agencies
      instead of public child welfare agencies or penal authorities. This fact might
      explain the higher disclosure rates.

PMID- 23884377
TI  - Psychometric validation of the Italian version of the I-QoL questionnaire:
      clinical and urodynamic findings.
AB  - INTRODUCTION AND HYPOTHESIS: The aim was to validate the Italian version of the
      Incontinence-Quality of Life questionnaire (I-QoL) in women with clinical and
      urodynamic urinary incontinence (UI). A secondary end point was to compare the
      results of women with reported UI, but negative urodynamic findings. METHODS: The
      Italian translation of the I-QoL was administered to 267 Italian women with
      pelvic organ prolapse < stage III, and who had undergone previous surgical or
      medical therapy for UI. Cronbach's alpha was calculated to assess internal
      consistency of the I-QoL items. Reproducibility was assessed using the intraclass
      correlation coefficient (ICC). Convergent validity involved comparison of I-QoL
      scores and the Short Form-36 Health questionnaire. RESULTS: One hundred and sixty
      seven patients were considered for the primary end point: 47 had a negative
      history of UI and a normal urodynamic test, 120 complained of UI confirmed by a
      urodynamic test, 59 had a positive history for UI and a urodynamic test negative
      for UI, and 35 patients not reporting UI had a positive urodynamic test. The I
      QoL score revealed that the QoL was lower in patients with reported UI,
      irrespective of urodynamic findings. The overall I-QoL summary score and
      subscales showed high internal consistency (alpha ranges from 0.88 to 0.96). ICC
      ranged from 0.98 to 0.99, demonstrating the stability of the scores. The physical
      domain of the I-QoL showed a 0.27 correlation with the physical functioning
      subscale of the SF-36. No significant difference in I-QoL scores was found among
      various types of UI. CONCLUSION: The Italian translated version of the I-QoL is
      reliable, consistent and a valid instrument for assessing impact on quality of
      life in Italian speaking women with UI.

PMID- 23884379
TI  - Bisacenaphthopyrazinoquinoxaline derivatives: synthesis, physical properties and
      applications as semiconductors for n-channel field effect transistors.
AB  - Several bisacenaphthopyrazinoquinoxaline (BAPQ) based derivatives 1-3 were
      synthesized by condensation between the acenaphthenequinones and 1,2,4,5
      tetraaminobenzene tetrahydrochloride. Their optical, electrochemical and self
      assembling properties are tuned by different substituents. Among them, compound 3
      possesses a homogeneously distributed low-lying LUMO due to the peripheral
      substitution with four cyano groups. The corresponding n-channel field effect
      transistors showed a field effect electron mobility of 5 * 10(-3) cm(2) V(-1) s(
      1).

PMID- 23884380
TI  - Thickness-dependent molecular arrangement and topography of ultrathin ionic
      liquid films on a silica surface.
AB  - The molecular arrangement and topography of ultrathin ionic liquids (ILs) on a
      silicon wafer have been studied by AFM and ARXPS, respectively. The results
      indicate a transition from an "anion-cation" layered (smooth) structure to a
      "drop-on-layer"/"sponge" (rough) structure when the film gets thicker, which can
      be attributed to the competition between solid/IL attraction and anion-cation
      cohesion. 

PMID- 23884378
TI  - Endothelin 1 in cancer: biological implications and therapeutic opportunities.
AB  - Activation of autocrine and paracrine signalling by endothelin 1 (ET1) binding to
      its receptors elicits pleiotropic effects on tumour cells and on the host
      microenvironment. This activation modulates cell proliferation, apoptosis,
      migration, epithelial-to-mesenchymal transition, chemoresistance and
      neovascularization, thus providing a strong rationale for targeting ET1 receptors
      in cancer. In this Review, we discuss the advances in our understanding of the
      diverse biological roles of ET1 in cancer and describe the latest preclinical and
      clinical progress that has been made using small-molecule antagonists of ET1
      receptors that inhibit ET1-driven signalling. 

PMID- 23884381
TI  - Pinched-flow hydrodynamic stretching of single-cells.
AB  - Reorganization of cytoskeletal networks, condensation and decondensation of
      chromatin, and other whole cell structural changes often accompany changes in
      cell state and can reflect underlying disease processes. As such, the observable
      mechanical properties, or mechanophenotype, which is closely linked to
      intracellular architecture, can be a useful label-free biomarker of disease. In
      order to make use of this biomarker, a tool to measure cell mechanical properties
      should accurately characterize clinical specimens that consist of heterogeneous
      cell populations or contain small diseased subpopulations. Because of the
      heterogeneity and potential for rare populations in clinical samples, single
      cell, high-throughput assays are ideally suited. Hydrodynamic stretching has
      recently emerged as a powerful method for carrying out mechanical phenotyping.
      Importantly, this method operates independently of molecular probes, reducing
      cost and sample preparation time, and yields information-rich signatures of cell
      populations through significant image analysis automation, promoting more
      widespread adoption. In this work, we present an alternative mode of hydrodynamic
      stretching where inertially-focused cells are squeezed in flow by perpendicular
      high-speed pinch flows that are extracted from the single inputted cell
      suspension. The pinched-flow stretching method reveals expected differences in
      cell deformability in two model systems. Furthermore, hydraulic circuit design is
      used to tune stretching forces and carry out multiple stretching modes (pinched
      flow and extensional) in the same microfluidic channel with a single fluid input.
      The ability to create a self-sheathing flow from a single input solution should
      have general utility for other cytometry systems and the pinched-flow design
      enables an order of magnitude higher throughput (65,000 cells s(-1)) compared to
      our previously reported deformability cytometry method, which will be especially
      useful for identification of rare cell populations in clinical body fluids in the
      future.

PMID- 23884382
TI  - Prognostic nutritional index predicts postoperative outcome in colorectal cancer.
AB  - BACKGROUND: The prognostic nutritional index (PNI), which is calculated based on
      the serum albumin concentration and peripheral blood lymphocyte count, is a
      useful tool for predicting short-term and long-term postoperative outcome in
      patients undergoing cancer surgery. However, few studies have investigated PNI in
      colorectal cancer surgery. We examined the ability of PNI to predict short- and
      long-term outcomes in patients with colorectal cancer. METHODS: This
      retrospective study included 365 patients who underwent resection for colorectal
      cancer. The prognostic nutritional status was calculated on the basis of
      admission data as follows: 10 * serum albumin (g/dl) + 0.005 * total lymphocyte
      count (per mm(3)). The primary outcomes measured were the impact of PNI on
      overall survival and postoperative complications. RESULTS: Kaplan-Meier analysis
      and the log rank test revealed that low PNI was significantly associated with
      poor survival (P < 0.0001). In multivariate analysis for survival, preoperative
      low PNI was an independent prognostic factor for poor survival: odds ratio: 2.25,
      95 % confidence interval 1.42-3.59). Moreover, low PNI significantly correlated
      with the incidence of postoperative complications, especially serious ones.
      CONCLUSIONS: Preoperative PNI is a useful predictor of postoperative
      complications and survival in patients with colorectal cancer.

PMID- 23884383
TI  - Comparison of peristomal adhesion formation between laparoscopic and open low
      anterior resection of rectal cancer.
AB  - BACKGROUND: Postoperative adhesions appear to be less common following
      laparoscopic surgery than after conventional open surgery. The purpose of this
      study was to compare the impact of laparoscopic and conventional open rectal
      surgery on peristomal adhesion formation. METHODS: We enrolled 97 subjects who
      were participants in a trial comparing open versus laparoscopic surgery for mid
      and low rectal cancer after neoadjuvant chemoradiotherapy. These patients had
      undergone rectal cancer surgery with ileostomy formation. Peristomal adhesions
      were assessed during ileostomy takedown using an adhesion grading system: (1) no
      adhesions or fine, filmy adhesions separable by blunt dissection; (2) dense
      adhesions, separable by sharp dissection; (3) very dense adhesions, resulting in
      enterotomy and/or requiring extension of the abdominal wall incision. RESULTS: A
      total of 57 patients underwent laparoscopic resection (group A) and 40 underwent
      open resection (group B). Operating time for ileostomy dissection was shorter in
      group A than in group B (14.6 vs. 19.8 min, respectively; p = 0.047). Dense
      adhesions (grades 2 and 3) were more common in group B (22/40, 55 %) than in
      group A (12/57, 21 %; p < 0.001). In particular, grade 3 adhesions were present
      only in group B (6/40). CONCLUSIONS: The present findings suggest that
      laparoscopic rectal surgery results in less peristomal adhesion formation than
      does conventional open surgery.

PMID- 23884385
TI  - Optimising a vortex fluidic device for controlling chemical reactivity and
      selectivity.
AB  - A vortex fluidic device (VFD) involving a rapidly rotating tube open at one end
      forms dynamic thin films at high rotational speed for finite sub-millilitre
      volumes of liquid, with shear within the films depending on the speed and
      orientation of the tube. Continuous flow operation of the VFD where jet feeds of
      solutions are directed to the closed end of the tube provide additional tuneable
      shear from the viscous drag as the liquid whirls along the tube. The versatility
      of this simple, low cost microfluidic device, which can operate under confined
      mode or continuous flow is demonstrated in accelerating organic reactions, for
      model Diels-Alder dimerization of cyclopentadienes, and sequential aldol and
      Michael addition reactions, in accessing unusual 2,4,6-triarylpyridines.
      Residence times are controllable for continuous flow processing with the viscous
      drag dominating the shear for flow rates >0.1 mL/min in a 10 mm diameter tube
      rotating at >2000 rpm. 

PMID- 23884387
TI  - Acute ingestion of beetroot bread increases endothelium-independent vasodilation
      and lowers diastolic blood pressure in healthy men: a randomized controlled
      trial.
AB  - Dietary nitrate, from beetroot, has been reported to lower blood pressure (BP) by
      the sequential reduction of nitrate to nitrite and further to NO in the
      circulation. However, the impact of beetroot on microvascular vasodilation and
      arterial stiffness is unknown. In addition, beetroot is consumed by only 4.5% of
      the UK population, whereas bread is a staple component of the diet. Thus, we
      investigated the acute effects of beetroot bread (BB) on microvascular
      vasodilation, arterial stiffness, and BP in healthy participants. Twenty-three
      healthy men received 200 g bread containing 100 g beetroot (1.1 mmol nitrate) or
      200 g control white bread (CB; 0 g beetroot, 0.01 mmol nitrate) in an acute,
      randomized, open-label, controlled crossover trial. The primary outcome was
      postprandial microvascular vasodilation measured by laser Doppler iontophoresis
      and the secondary outcomes were arterial stiffness measured by Pulse Wave
      Analysis and Velocity and ambulatory BP measured at regular intervals for a total
      period of 6 h. Plasma nitrate and nitrite were measured at regular intervals for
      a total period of 7 h. The incremental area under the curve (0-6 h after
      ingestion of bread) for endothelium-independent vasodilation was greater (P =
      0.017) and lower for diastolic BP (DBP; P = 0.032) but not systolic (P = 0.99) BP
      after BB compared with CB. These effects occurred in conjunction with increases
      in plasma and urinary nitrate (P < 0.0001) and nitrite (P < 0.001). BB acutely
      increased endothelium-independent vasodilation and decreased DBP. Therefore,
      enriching bread with beetroot may be a suitable vehicle to increase intakes of
      cardioprotective beetroot in the diet and may provide new therapeutic
      perspectives in the management of hypertension. 

PMID- 23884386
TI  - Concurrent physical activity modifies the association between n3 long-chain fatty
      acids and cardiometabolic risk in midlife adults.
AB  - Greater consumption of n3 (omega3) polyunsaturated fatty acids eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA) can reduce risk for cardiovascular
      disease events, yet their effects on metabolic risk factors and diabetes remain
      unclear. This cross-sectional study used a community volunteer sample to test
      whether the associations between n3 fatty acids and cardiometabolic risk vary as
      a function of physical activity. Participants were 344 generally healthy adults,
      30-54 y of age, not taking fish oil supplements or confounding medications. Serum
      phospholipid EPA and DHA were used together (EPA+DHA) as a biomarker of n3 fatty
      acid exposure. Cardiometabolic risk was calculated as a continuous measure based
      on standardized distributions of blood pressure, waist circumference, HDL
      cholesterol, triglycerides, glucose, and a simple count of risk factors. Insulin
      resistance was estimated from the homeostatic model assessment. Physical activity
      was found to predict cardiometabolic risk (P <= 0.02) and insulin resistance (P
      <= 0.02) and to moderate the association between EPA+DHA and both cardiometabolic
      risk (P-interaction <= 0.02) and insulin resistance (P-interaction <= 0.02).
      Specifically, higher EPA+DHA was associated with lower cardiometabolic risk and
      insulin resistance in persons engaged in regular physical activity but not in
      relatively inactive individuals. These findings were noted in several components
      of cardiometabolic risk, in men and women separately, and in models adjusted for
      overall diet quality. In midlife adults, habitual physical activity may be
      necessary to unmask the salutary effects of n3 fatty acids on cardiometabolic
      risk and insulin resistance. 

PMID- 23884388
TI  - Total iron absorption by young women from iron-biofortified pearl millet
      composite meals is double that from regular millet meals but less than that from
      post-harvest iron-fortified millet meals.
AB  - Iron biofortification of pearl millet (Pennisetum glaucum) is a promising
      approach to combat iron deficiency (ID) in the millet-consuming communities of
      developing countries. To evaluate the potential of iron-biofortified millet to
      provide additional bioavailable iron compared with regular millet and post
      harvest iron-fortified millet, an iron absorption study was conducted in 20
      Beninese women with marginal iron status. Composite test meals consisting of
      millet paste based on regular-iron, iron-biofortified, or post-harvest iron
      fortified pearl millet flour accompanied by a leafy vegetable sauce or an okra
      sauce were fed as multiple meals for 5 d. Iron absorption was measured as
      erythrocyte incorporation of stable iron isotopes. Fractional iron absorption
      from test meals based on regular-iron millet (7.5%) did not differ from iron
      biofortified millet meals (7.5%; P = 1.0), resulting in a higher quantity of
      total iron absorbed from the meals based on iron-biofortified millet (1125 vs.
      527 MUg; P < 0.0001). Fractional iron absorption from post-harvest iron-fortified
      millet meals (10.4%) was higher than from regular-iron and iron-biofortified
      millet meals (P < 0.05 and P < 0.01, respectively), resulting in a higher
      quantity of total iron absorbed from the post-harvest iron-fortified millet meals
      (1500 MUg; P < 0.0001 and P < 0.05, respectively). Results indicate that
      consumption of iron-biofortified millet would double the amount of iron absorbed
      and, although fractional absorption of iron from biofortification is less than
      that from fortification, iron-biofortified millet should be highly effective in
      combatting ID in millet-consuming populations. 

PMID- 23884389
TI  - Ensuring the high quality of journal of nutrition publications.

PMID- 23884390
TI  - Vitamin D supplementation affects serum high-sensitivity C-reactive protein,
      insulin resistance, and biomarkers of oxidative stress in pregnant women.
AB  - Unfavorable metabolic profiles and oxidative stress in pregnancy are associated
      with several complications. This study was conducted to determine the effects of
      vitamin D supplementation on serum concentrations of high-sensitivity C-reactive
      protein (hs-CRP), metabolic profiles, and biomarkers of oxidative stress in
      healthy pregnant women. This randomized, double-blind, placebo-controlled
      clinical trial was conducted in 48 pregnant women aged 18-40 y old at 25 wk of
      gestation. Participants were randomly assigned to receive either 400 IU/d
      cholecalciferol supplements (n = 24) or placebo (n = 24) for 9 wk. Fasting blood
      samples were taken at study baseline and after 9 wk of intervention to quantify
      serum concentrations of hs-CRP, lipid concentrations, insulin, and biomarkers of
      oxidative stress. After 9 wk of intervention, the increases in serum 25
      hydroxyvitamin D and calcium concentrations were greater in the vitamin D group
      (+3.7 MUg/L and +0.20 mg/dL, respectively) than in the placebo group (-1.2 MUg/L
      and -0.12 mg/dL, respectively; P < 0.001 for both). Vitamin D supplementation
      resulted in a significant decrease in serum hs-CRP (vitamin D vs. placebo groups:
      -1.41 vs. +1.50 MUg/mL; P-interaction = 0.01) and insulin concentrations (vitamin
      D vs. placebo groups: -1.0 vs. +2.6 MUIU/mL; P-interaction = 0.04) and a
      significant increase in the Quantitative Insulin Sensitivity Check Index score
      (vitamin D vs. placebo groups: +0.02 vs. -0.02; P-interaction = 0.006), plasma
      total antioxidant capacity (vitamin D vs. placebo groups: +152 vs. -20 mmol/L; P
      interaction = 0.002), and total glutathione concentrations (vitamin D vs. placebo
      groups: +205 vs. -32 MUmol/L; P-interaction = 0.02) compared with placebo. Intake
      of vitamin D supplements led to a significant decrease in fasting plasma glucose
      (vitamin D vs. placebo groups: -0.65 vs. -0.12 mmol/L; P-interaction = 0.01),
      systolic blood pressure (vitamin D vs. placebo groups: -0.2 vs. +5.5 mm Hg; P
      interaction = 0.01), and diastolic blood pressure (vitamin D vs. placebo groups: 
      0.4 vs. +3.1 mm Hg; P-interaction = 0.01) compared with placebo. In conclusion,
      vitamin D supplementation for 9 wk among pregnant women has beneficial effects on
      metabolic status. 

PMID- 23884392
TI  - Hyperopic shift in refraction in adults with aging.

PMID- 23884391
TI  - Repeatability of visual function measures in age-related macular degeneration.
AB  - PURPOSE: To assess repeatability of visual function measures in patients with
      early, intermediate or late age-related macular degeneration (AMD) without active
      neovascular disease in the study eye, but active neovascular AMD in the fellow
      eye. METHODS: One hundred subjects from an ongoing trial were screened for this
      study in which their LogMAR acuity, contrast sensitivity and reading performance
      were assessed using standardised protocols by trained optometrists. The same
      measures were repeated one month later and repeatability of the visual functions
      assessed. RESULTS: Data from 83 subjects satisfied inclusion criteria for
      analysis. Coefficient of repeatability was 14.9 letters for LogMAR visual acuity
      , 7.2 letters for Pelli Robson contrast sensitivity, 0.72 for LogMAR reading
      acuity, 110.4 words/ min for reading speed and 0.67 for LogMAR critical print
      size. Intraclass correlation coefficients allowed comparison between measures and
      were found to be 0.96 for LogMAR visual acuity, 0.93 for contrast sensitivity,
      0.75 for LogMAR reading acuity, 0.79 for reading speed and 0.74 for LogMAR
      critical print size. Coefficients of variation were 9.4 %, 10.7 %, 48.4 %, 28.4 %
      and 31.8 % respectively. CONCLUSIONS: We found coefficients of repeatability that
      concurred with previous studies demonstrating variability of visual functions in
      patients with AMD. In addition, we found intraclass correlation coefficients to
      be better with visual acuity and contrast sensitivity than with measures of
      reading performance.

PMID- 23884393
TI  - Floral longevity and autonomous selfing are altered by pollination and water
      availability in Collinsia heterophylla.
AB  - BACKGROUND AND AIMS: A plant investing in reproduction partitions resources
      between flowering and seed production. Under resource limitation, altered
      allocations may result in floral trait variations, leading to compromised
      fecundity. Floral longevity and timing of selfing are often the traits most
      likely to be affected. The duration of corolla retention determines whether
      fecundity results from outcrossing or by delayed selfing-mediated reproductive
      assurance. In this study, the role of pollination schedules and soil water
      availability on floral longevity and seed production is tested in Collinsia
      heterophylla (Plantaginaceae). METHODS: Using three different watering regimes
      and pollination schedules, effects on floral longevity and seed production were
      studied in this protandrous, flowering annual. KEY RESULTS: The results reveal
      that soil water status and pollination together influence floral longevity with
      low soil water and hand-pollinations early in the floral lifespan reducing
      longevity. However, early pollinations under excess water did not extend
      longevity, implying that resource surplus does not lengthen the outcrossing
      period. The results also indicate that pollen receipt, a reliable cue for
      fecundity, accelerates flower drop. Early corolla abscission under drought stress
      could potentially exacerbate sexual conflict in this protandrous, hermaphroditic
      species by ensuring self-pollen paternity and enabling male control of floral
      longevity. While pollination schedules did not affect fecundity, water stress
      reduced per-capita seed numbers. Unmanipulated flowers underwent delayed
      autonomous selfing, producing very few seeds, suggesting that inbreeding
      depression may limit benefits of selfing. CONCLUSIONS: In plants where herkogamy
      and dichogamy facilitate outcrossing, floral longevity determines reproductive
      success and mating system. Reduction in longevity under drought suggests a strong
      environmental effect that could potentially alter the preferred breeding mode in
      this mixed-mated species. Extrapolating the findings to unpredictable global
      drought cycles, it is suggested that in addition to reducing yield, water stress
      may influence the evolutionary trajectory of plant mating system.

PMID- 23884394
TI  - Comparative anatomy of the floral elaiophore in representatives of the newly re
      circumscribed Gomesa and Oncidium clades (Orchidaceae: Oncidiinae).
AB  - BACKGROUND AND AIMS: Recently, molecular approaches have been used to investigate
      the phylogeny of Oncidiinae. This has resulted in the transfer of taxa previously
      considered to be species of Oncidium Sw. into Gomesa R. Br. and the re
      circumscription of both genera. In this study, the structure of the floral
      elaiophore (oil gland) is described and compared for Gomesa echinata (Barb.
      Rodr.) M.W. Chase & N.H. Williams, G. ranifera (Lindl.) M.W. Chase & N.H.
      Williams, Oncidium amazonicum (Schltr.) M.W. Chase & N.H. Williams and O.
      oxyceras (Koniger & J.G. Weinm.) M.W. Chase & N.H. Williams in order to determine
      whether phylogenetic revision is supported by differences in its anatomy.
      METHODS: The floral elaiophore structure was examined and compared at three
      developmental stages (closed bud, first day of anthesis and final stage of
      anthesis) for all four species using light microscopy, fluorescence microscopy,
      scanning electron microscopy, transmission electron microscopy and
      histochemistry. KEY RESULTS: In all species investigated, the floral elaiophore
      occurs on the labellar callus and is of the epithelial type, comprising cuboidal
      to palisade-like, secretory epidermal cells and a layer of sub-epidermal cells,
      both tissues enclosing ground parenchyma supplied with collateral vascular
      bundles and containing idioblasts, often with raphides or phenolic contents. A bi
      layered cuticle comprising an outer, lamellate and an inner, reticulate layer is
      present, and sub-cuticular accumulation of secreted material results in
      distension of the cuticle. Secretion-filled cavities are present at anthesis in
      the elaiophore cell walls and, in most species, the outer, tangential walls of
      the elaiophore have small, peg-like projections that protrude into the cytoplasm.
      In all taxa examined, the elaiophore organelle complement, especially the smooth
      endoplasmic reticulum (SER), is typical of lipid-secreting cells. CONCLUSIONS: In
      terms of location, morphology, anatomy and ultrastructure, the floral elaiophores
      of both Gomesa and Oncidium species examined are very similar, and distinction
      between these genera is not possible based on elaiophore features alone.
      Furthermore, many of these elaiophore characters are shared with representatives
      of other clades of Oncidiinae, including the Ornithocephalus clade. Consequently,
      elaiophores are considered homoplasious and of limited value in investigating the
      phylogeny of this subtribe.

PMID- 23884395
TI  - Pair-flowered cymes in the Lamiales: structure, distribution and origin.
AB  - BACKGROUND AND AIMS: In the Lamiales, indeterminate thyrses (made up of axillary
      cymes) represent a significant inflorescence type. However, it has been largely
      overlooked that there occur two types of cymes: (1) ordinary cymes, and (2) 'pair
      flowered cymes' (PFCs), with a flower pair (terminal and front flower) topping
      each cyme unit. PFCs are unique to the Lamiales and their distribution, origin
      and phylogeny are not well understood. METHODS: The Lamiales are screened as to
      the occurrence of PFCs, ordinary cymes and single flowers (constituting racemic
      inflorescences). KEY RESULTS: PFCs are shown to exhibit a considerable
      morphological and developmental diversity and are documented to occur in four
      neighbouring taxa of Lamiales: Calceolariaceae, Sanango, Gesneriaceae and
      Plantaginaceae. They are omnipresent in the Calceolariaceae and almost so in the
      Gesneriaceae. In the Plantaginaceae, PFCs are restricted to the small sister
      tribes Russelieae and Cheloneae (while the large remainder has single flowers in
      the leaf/bract axils; ordinary cymes do not occur). Regarding the origin of PFCs,
      the inflorescences of the genus Peltanthera (unplaced as to family; sister to
      Calceolariaceae, Sanango and Gesneriaceae in most molecular phylogenies) support
      the idea that PFCs have originated from paniculate systems, with the front
      flowers representing remnant flowers. CONCLUSIONS: From the exclusive occurrence
      of PFCs in the Lamiales and the proximity of the respective taxa in molecular
      phylogenies it may be expected that PFCs have originated once, representing a
      synapomorphy for this group of taxa and fading out within the Plantaginaceae.
      However, molecular evidence is ambiguous. Depending on the position of
      Peltanthera (depending in turn on the kind and number of genes and taxa analysed)
      a single, a double (the most probable scenario) or a triple origin appears
      conceivable.

PMID- 23884396
TI  - Conditional cold avoidance drives between-population variation in germination
      behaviour in Calluna vulgaris.
AB  - BACKGROUND AND AIMS: Across their range, widely distributed species are exposed
      to a variety of climatic and other environmental conditions, and accordingly may
      display variation in life history strategies. For seed germination in cold
      climates, two contrasting responses to variation in winter temperature have been
      documented: first, an increased ability to germinate at low temperatures (cold
      tolerance) as winter temperatures decrease, and secondly a reduced ability to
      germinate at low temperatures (cold avoidance) that concentrates germination
      towards the warmer parts of the season. METHODS: Germination responses were
      tested for Calluna vulgaris, the dominant species of European heathlands, from
      ten populations collected along broad-scale bioclimatic gradients (latitude,
      altitude) in Norway, covering a substantial fraction of the species' climatic
      range. Incubation treatments varied from 10 to 25  degrees C, and germination
      performance across populations was analysed in relation to temperature conditions
      at the seed collection locations. KEY RESULTS: Seeds from all populations
      germinated rapidly and to high final percentages under the warmer incubation
      temperatures. Under low incubation temperatures, cold-climate populations had
      significantly lower germination rates and percentages than warm-climate
      populations. While germination rates and percentages also increased with seed
      mass, seed mass did not vary along the climatic gradients, and therefore did not
      explain the variation in germination responses. CONCLUSIONS: Variation in
      germination responses among Calluna populations was consistent with increased
      temperature requirements for germination towards colder climates, indicating a
      cold-avoidance germination strategy conditional on the temperature at the seeds'
      origin. Along a gradient of increasing temperatures this suggests a shift in
      selection pressures on germination from climatic adversity (i.e. low temperatures
      and potential frost risk in early or late season) to competitive performance and
      better exploitation of the entire growing season.

PMID- 23884397
TI  - Ecological significance and complexity of N-source preference in plants.
AB  - BACKGROUND: Plants can utilize two major forms of inorganic N: NO3(-) (nitrate)
      and NH4(+) (ammonium). In some cases, the preference of one form over another
      (denoted as beta) can appear to be quite pronounced for a plant species, and can
      be an important determinant and predictor of its distribution and interactions
      with other species. In many other cases, however, assignment of preference is not
      so straightforward and must take into account a wide array of complex
      physiological and environmental features, which interact in ways that are still
      not well understood. SCOPE: This Viewpoint presents a discussion of the key, and
      often co-occurring, factors that join to produce the complex phenotypic composite
      referred to by the deceptively simple term 'N-source preference'. CONCLUSIONS: N
      source preference is much more complex a biological phenomenon than is often
      assumed, and general models predicting how it will influence ecological processes
      will need to be much more sophisticated than those that have been so far
      developed.

PMID- 23884398
TI  - Threshing efficiency as an incentive for rapid domestication of emmer wheat.
AB  - BACKGROUND AND AIMS: The harvesting method of wild and cultivated cereals has
      long been recognized as an important factor in the emergence of domesticated non
      shattering ear genotypes. This study aimed to quantify the effects of spike
      brittleness and threshability on threshing time and efficiency in emmer wheat,
      and to evaluate the implications of post-harvest processes on domestication of
      cereals in the Near East. METHODS: A diverse collection of tetraploid wheat
      genotypes, consisting of Triticum turgidum ssp. dicoccoides - the wild progenitor
      of domesticated wheat - traditional landraces, modern cultivars (T. turgidum ssp.
      durum) and 150 recombinant (wild * modern) inbred lines, was used in replicated
      controlled threshing experiments to quantify the effects of spike brittleness and
      threshability on threshing time and efficiency. KEY RESULTS: The transition from
      a brittle hulled wild phenotype to non-brittle hulled phenotype (landraces) was
      associated with an approx. 30 % reduction in threshing time, whereas the
      transition from the latter to non-brittle free-threshing cultivars was associated
      with an approx. 85 % reduction in threshing time. Similar trends were obtained
      with groups of recombinant inbred lines showing extreme phenotypes of brittleness
      and threshability. CONCLUSIONS: In tetraploid wheat, both non-brittle spike and
      free-threshing are labour-saving traits that increase the efficiency of post
      harvest processing, which could have been an incentive for rapid domestication of
      the Near Eastern cereals, thus refuting the recently proposed hypothesis
      regarding extra labour associated with the domesticated phenotype (non-brittle
      spike) and its presumed role in extending the domestication episode time frame.

PMID- 23884399
TI  - Maternal smoking and conduct disorder in the offspring.

PMID- 23884400
TI  - Multi-resonant plasmonic nanodome arrays for label-free biosensing applications.
AB  - The characteristics and utility of plasmonic nanodome arrays capable of
      supporting multiple resonance modes are described. A low-cost, large-area replica
      molding process is used to produce, on flexible plastic substrates, two
      dimensional periodic arrays of cylinders that are subsequently coated with SiO2
      and Ag thin films to form dome-shaped structures, with 14 nm spacing between the
      features, in a precise and reproducible fashion. Three distinct optical resonance
      modes, a grating diffraction mode and two localized surface plasmon resonance
      (LSPR) modes, are observed experimentally and confirmed by finite-difference-time
      domain (FDTD) modeling which is used to calculate the electromagnetic field
      distribution of each resonance around the nanodome array structure. Each optical
      mode is characterized by measuring sensitivity to bulk refractive index changes
      and to surface effects, which are examined using stacked polyelectrolyte layers.
      The utility of the plasmonic nanodome array as a functional interface for
      biosensing applications is demonstrated by performing a bioassay to measure the
      binding affinity constant between protein A and human immunoglobulin G (IgG) as a
      model system. The nanoreplica molding process presented in this work allows for
      simple, inexpensive, high-throughput fabrication of nanoscale plasmonic
      structures over a large surface area (120 * 120 mm(2)) without the requirement
      for high resolution lithography or additional processes such as etching or
      liftoff. The availability of multiple resonant modes, each with different optical
      properties, allows the nanodome array surface to address a wide range of
      biosensing problems with various target analytes of different sizes and
      configurations. 

PMID- 23884401
TI  - Use the duodenum, it's right there: a retrospective cohort study comparing
      biliary reconstruction using either the jejunum or the duodenum.
AB  - IMPORTANCE: This is the largest series to date comparing end-to-side biliary
      reconstruction for all indications performed using either the duodenum or jejunum
      and with at least 2-year follow-up. OBJECTIVE: To demonstrate that duodenal
      anastomoses for biliary reconstruction are at least as safe and effective as Roux
      en-Y jejunal anastomoses, with the benefits of operative simplicity and ease of
      postoperative endoscopic evaluation. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective record review with telephone survey of patients undergoing
      nonpalliative biliary reconstruction in the hepatopancreatobiliary surgery
      division of a high-volume tertiary care facility. INTERVENTIONS: Biliary
      reconstruction via either end-to-side Roux-en-Y jejunal anastomosis or direct
      duodenal anastomosis. MAIN OUTCOMES AND MEASURES: The primary end points were
      anastomosis-related complications (leak, cholangitis, bile gastritis, or
      stricture), and the secondary end points were overall complications, endoscopic
      or radiologic interventions, readmissions, and death. RESULTS: Ninety-six
      nonpalliative biliary reconstructions were performed between February 1, 2000,
      and November 23, 2011 for bile duct injury, cholangiocarcinoma, choledochal
      cysts, or benign strictures; the procedures included 59 duodenal reconstructions
      and 37 Roux-en-Y jejunal reconstructions. The groups were similar with regard to
      demographics, operative indications, postoperative length of stay, and mortality
      rates. However, anastomosis-related complications (leaks, cholangitis, or
      strictures) were fewer in the duodenal than the jejunal cohort (7 patients [12%]
      vs 13 [35%]; P = .009). Of patients with stricture, 5 of 9 in the jejunal cohort
      required percutaneous transhepatic access for management compared with only 1 of
      2 in the duodenal cohort. CONCLUSIONS AND RELEVANCE: Duodenal anastomosis is a
      safe, simple, and often preferable method for biliary reconstruction. This
      anastomosis can successfully be performed to all levels of the biliary tree with
      low rates of leak, stricture, cholangitis, and bile gastritis. When anastomotic
      complications do occur, there is less need for transhepatic intervention because
      of easier endoscopic access.

PMID- 23884403
TI  - Wound infusion of bupivacaine following radical retropubic prostatectomy.

PMID- 23884405
TI  - Reply to: ED50 of sevoflurane for LMA Supreme insertion: reliability!

PMID- 23884404
TI  - Performance of acceleromyography with a short and light TOF-tube compared with
      mechanomyography: a clinical comparison.
AB  - BACKGROUND: Disturbances in the thumb's movement interfere with the functioning
      of acceleromyography in many clinical settings. The short and light (SL) train-of
      four (TOF)-Tube is a new version of a rigid tubular device that was designed to
      protect the thumb from external disturbances during surgery, even when the hand
      is not accessible by the anaesthesiologist. OBJECTIVE: To compare the precision
      and performance of acceleromyography performed with the aid of the SL TOF-Tube
      (AMGTT) with standard isometric mechanomyography (MMG). DESIGN: Simultaneous arm
      to-arm comparison of both methods in the same anaesthetised patient. SETTING: A
      monocentric study, performed from September 2007 to June 2008. PATIENTS: Nineteen
      ASA I to II patients scheduled to undergo lower limb orthopaedic surgery under
      general anaesthesia. INTERVENTION: Neuromuscular transmission monitoring during
      baseline, onset and spontaneous recovery of rocuronium-induced neuromuscular
      block. MAIN OUTCOME MEASURES: Initial baseline and repeatability coefficients
      were assessed during 10 consecutive measurements of the first twitch height (T1)
      and TOF T4/T1 ratio and compared using a z test. The spontaneous recoveries of
      defined blockade levels (onset, T1 25% of initial calibration and TOF ratio 0.9)
      were compared in terms of duration and intensity. Agreement between both
      techniques was assessed by the Bland-Altman method. RESULTS: The mean +/- SD
      control TOF ratios were 98 +/- 1% (MMG) and 103 +/- 2% (AMGTT). The repeatability
      coefficients were higher (P < 0.001) and the onset was longer (mean 0.44 min) (P
      < 0.001) when they were measured by AMGTT. The recoveries of T1 25% and TOF ratio
      0.9 were not significantly different between the two methods, and the limits of
      agreement were in the usual range of contralateral comparisons (-19 and +24% for
      TOF ratio 0.9). CONCLUSION: Compared with mechanomyography, acceleromyography
      performed with the aid of an SL TOF-Tube offered acceptable precision and
      equivalent performance during neuromuscular block recovery.

PMID- 23884406
TI  - Reversible switching of the electronic ground state in a pentacoordinated Cu(II)
      complex.
AB  - An easy reversible switching of the electronic ground state in a pentacoordinated
      copper(II) complex is reported for the first time. The simple protonation of a
      carboxylic group in a Cu(II) complex with a {dx(2)-y(2)}(1) electronic
      configuration leads to a flip of the ground electronic configuration from {dx(2)
      y(2)}(1) to {dz(2)}(1) in the metal ion.

PMID- 23884402
TI  - Nutrition and neurodevelopment in children: focus on NUTRIMENTHE project.
AB  - There is growing evidence that early nutrition affects later cognitive
      performance. The idea that the diet of mothers, infants, and children could
      affect later mental performance has major implications for public health practice
      and policy development and for our understanding of human biology as well as for
      food product development, economic progress, and future wealth creation. To date,
      however, much of the evidence is from animal, retrospective studies and short
      term nutritional intervention studies in humans. The positive effect of
      micronutrients on health, especially of pregnant women eating well to maximise
      their child's cognitive and behavioural outcomes, is commonly acknowledged. The
      current evidence of an association between gestational nutrition and brain
      development in healthy children is more credible for folate, n-3 fatty acids, and
      iron. Recent findings highlight the fact that single-nutrient supplementation is
      less adequate than supplementation with more complex formulae. However, the
      optimal content of micronutrient supplementation and whether there is a long-term
      impact on child's neurodevelopment needs to be investigated further. Moreover, it
      is also evident that future studies should take into account genetic
      heterogeneity when evaluating nutritional effects and also nutritional
      recommendations. The objective of the present review is to provide a background
      and update on the current knowledge linking nutrition to cognition and behaviour
      in children, and to show how the large collaborative European Project NUTRIMENTHE
      is working towards this aim. 

PMID- 23884407
TI  - A novel microfluidic platform with stable concentration gradient for on chip cell
      culture and screening assays.
AB  - In this work a novel microfluidic platform for cell culture and assay is
      developed. On the chip a static cell culture region is coupled with dynamic
      fluidic nutrition supply structures. The cell culture unit has a sandwich
      structure with liquid channels on the top, the cell culture reservoir in the
      middle and gas channels on the bottom. Samples can be easily loaded into the
      reservoir and exchange constantly with the external liquid environment by
      diffusion. Since the flow direction is perpendicular to the liquid channel on the
      top of the reservoir, the cells in the reservoir are shielded from shear-force.
      By assembling the basic units into an array, a steady concentration gradient can
      be generated. Cell culture models both for continuous perfusion and one-off
      perfusion were established on the chip. Both adherent and suspended cells were
      successfully cultured on the chip in 2D and 3D culture modes. After culturing,
      the trapped cells were recovered for use in a later assay. As a competitive
      candidate for a standard cell culture and assay platform, this chip is also
      adaptable for cytotoxicity and cell growth assays. 

PMID- 23884408
TI  - N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) promote growth and
      inhibit differentiation of glioma stem-like cells.
AB  - Metabolic reprogramming is a pathological feature of cancer and a driver of tumor
      cell transformation. N-Acetylaspartate (NAA) is one of the most abundant amino
      acid derivatives in the brain and serves as a source of metabolic acetate for
      oligodendrocyte myelination and protein/histone acetylation or a precursor for
      the synthesis of the neurotransmitter N-acetylaspartylglutamate (NAAG). NAA and
      NAAG as well as aspartoacylase (ASPA), the enzyme responsible for NAA
      degradation, are significantly reduced in glioma tumors, suggesting a possible
      role for decreased acetate metabolism in tumorigenesis. This study sought to
      examine the effects of NAA and NAAG on primary tumor-derived glioma stem-like
      cells (GSCs) from oligodendroglioma as well as proneural and mesenchymal
      glioblastoma, relative to oligodendrocyte progenitor cells (Oli-Neu). Although
      the NAA dicarboxylate transporter NaDC3 is primarily thought to be expressed by
      astrocytes, all cell lines expressed NaDC3 and, thus, are capable of NAA up-take.
      Treatment with NAA or NAAG significantly increased GSC growth and suppressed
      differentiation of Oli-Neu cells and proneural GSCs. Interestingly, ASPA was
      expressed in both the cytosol and nuclei of GSCs and exhibited greatest nuclear
      immunoreactivity in differentiation-resistant GSCs. Both NAA and NAAG elicited
      the expression of a novel immunoreactive ASPA species in select GSC nuclei,
      suggesting differential ASPA regulation in response to these metabolites.
      Therefore, this study highlights a potential role for nuclear ASPA expression in
      GSC malignancy and suggests that the use of NAA or NAAG is not an appropriate
      therapeutic approach to increase acetate bioavailability in glioma. Thus, an
      alternative acetate source is required. 

PMID- 23884409
TI  - Structural characterization of the bacteriophage T7 tail machinery.
AB  - Most bacterial viruses need a specialized machinery, called "tail," to inject
      their genomes inside the bacterial cytoplasm without disrupting the cellular
      integrity. Bacteriophage T7 is a well characterized member of the Podoviridae
      family infecting Escherichia coli, and it has a short noncontractile tail that
      assembles sequentially on the viral head after DNA packaging. The T7 tail is a
      complex of around 2.7 MDa composed of at least four proteins as follows: the
      connector (gene product 8, gp8), the tail tubular proteins gp11 and gp12, and the
      fibers (gp17). Using cryo-electron microscopy and single particle image
      reconstruction techniques, we have determined the precise topology of the tail
      proteins by comparing the structure of the T7 tail extracted from viruses and a
      complex formed by recombinant gp8, gp11, and gp12 proteins. Furthermore, the
      order of assembly of the structural components within the complex was deduced
      from interaction assays with cloned and purified tail proteins. The existence of
      common folds among similar tail proteins allowed us to obtain pseudo-atomic
      threaded models of gp8 (connector) and gp11 (gatekeeper) proteins, which were
      docked into the corresponding cryo-EM volumes of the tail complex. This pseudo
      atomic model of the connector-gatekeeper interaction revealed the existence of a
      common molecular architecture among viruses belonging to the three tailed
      bacteriophage families, strongly suggesting that a common molecular mechanism has
      been favored during evolution to coordinate the transition between DNA packaging
      and tail assembly. 

PMID- 23884410
TI  - Membrane-permeable C-terminal dopamine transporter peptides attenuate amphetamine
      evoked dopamine release.
AB  - The dopamine transporter (DAT) is responsible for sequestration of extracellular
      dopamine (DA). The psychostimulant amphetamine (AMPH) is a DAT substrate, which
      is actively transported into the nerve terminal, eliciting vesicular depletion
      and reversal of DA transport via DAT. Here, we investigate the role of the DAT C
      terminus in AMPH-evoked DA efflux using cell-permeant dominant-negative peptides.
      A peptide, which corresponded to the last 24 C-terminal residues of DAT (TAT-C24
      DAT) and thereby contained the Ca(2+)-calmodulin-dependent protein kinase IIalpha
      (CaMKIIalpha) binding domain and the PSD-95/Discs-large/ZO-1 (PDZ)-binding
      sequence of DAT, was made membrane-permeable by fusing it to the cell membrane
      transduction domain of the HIV-1 Tat protein (TAT-C24WT). The ability of TAT
      C24WT but not a scrambled peptide (TAT-C24Scr) to block the CaMKIIalpha-DAT
      interaction was supported by co-immunoprecipitation experiments in heterologous
      cells. In heterologous cells, we also found that TAT-C24WT, but not TAT-C24Scr,
      decreased AMPH-evoked 1-methyl-4-phenylpyridinium efflux. Moreover,
      chronoamperometric recordings in striatum revealed diminished AMPH-evoked DA
      efflux in mice preinjected with TAT-C24WT. Both in heterologous cells and in
      striatum, the peptide did not further inhibit efflux upon KN-93-mediated
      inhibition of CaMKIIalpha activity, consistent with a dominant-negative action
      preventing binding of CaMKIIalpha to the DAT C terminus. This was further
      supported by the ability of a peptide with perturbed PDZ-binding sequence, but
      preserved CaMKIIalpha binding (TAT-C24AAA), to diminish AMPH-evoked DA efflux in
      vivo to the same extent as TAT-C24WT. Finally, AMPH-induced locomotor
      hyperactivity was attenuated following systemic administration of TAT-C24WT but
      not TAT-C24Scr. Summarized, our findings substantiate that DAT C-terminal protein
      protein interactions are critical for AMPH-evoked DA efflux and suggest that it
      may be possible to target protein-protein interactions to modulate transporter
      function and interfere with psychostimulant effects. 

PMID- 23884411
TI  - Negative elongation factor (NELF) coordinates RNA polymerase II pausing,
      premature termination, and chromatin remodeling to regulate HIV transcription.
AB  - A barrier to eradicating HIV infection is targeting and eliminating latently
      infected cells. Events that contribute to HIV transcriptional latency include
      repressive chromatin structure, transcriptional interference, the inability of
      Tat to recruit positive transcription factor b, and poor processivity of RNA
      polymerase II (RNAP II). In this study, we investigated mechanisms by which
      negative elongation factor (NELF) establishes and maintains HIV latency. Negative
      elongation factor (NELF) induces RNAP II promoter proximal pausing and limits
      provirus expression in HIV-infected primary CD4(+) T cells. Decreasing NELF
      expression overcomes RNAP II pausing to enhance HIV transcription elongation in
      infected primary T cells, demonstrating the importance of pausing in repressing
      HIV transcription. We also show that RNAP II pausing is coupled to premature
      transcription termination and chromatin remodeling. NELF interacts with Pcf11, a
      transcription termination factor, and diminishing Pcf11 in primary CD4(+) T cells
      induces HIV transcription elongation. In addition, we identify NCoR1-GPS2-HDAC3
      as a NELF-interacting corepressor complex that is associated with repressed HIV
      long terminal repeats. We propose a model in which NELF recruits Pcf11 and NCoR1
      GPS2-HDAC3 to paused RNAP II, reinforcing repression of HIV transcription and
      establishing a critical checkpoint for HIV transcription and latency. 

PMID- 23884412
TI  - The Bcl-2 protein family member Bok binds to the coupling domain of inositol
      1,4,5-trisphosphate receptors and protects them from proteolytic cleavage.
AB  - Bok is a member of the Bcl-2 protein family that controls intrinsic apoptosis.
      Bok is most closely related to the pro-apoptotic proteins Bak and Bax, but in
      contrast to Bak and Bax, very little is known about its cellular role. Here we
      report that Bok binds strongly and constitutively to inositol 1,4,5-trisphosphate
      receptors (IP3Rs), proteins that form tetrameric calcium channels in the
      endoplasmic reticulum (ER) membrane and govern the release of ER calcium stores.
      Bok binds most strongly to IP3R1 and IP3R2, and barely to IP3R3, and essentially
      all cellular Bok is IP3R bound in cells that express substantial amounts of
      IP3Rs. Binding to IP3Rs appears to be mediated by the putative BH4 domain of Bok
      and the docking site localizes to a small region within the coupling domain of
      IP3Rs (amino acids 1895-1903 of IP3R1) that is adjacent to numerous regulatory
      sites, including sites for proteolysis. With regard to the possible role of Bok
      IP3R binding, the following was observed: (i) Bok does not appear to control the
      ability of IP3Rs to release ER calcium stores, (ii) Bok regulates IP3R
      expression, (iii) persistent activation of inositol 1,4,5-trisphosphate-dependent
      cell signaling causes Bok degradation by the ubiquitin-proteasome pathway, in a
      manner that parallels IP3R degradation, and (iv) Bok protects IP3Rs from
      proteolysis, either by chymotrypsin in vitro or by caspase-3 in vivo during
      apoptosis. Overall, these data show that Bok binds strongly and constitutively to
      IP3Rs and that the most significant consequence of this binding appears to be
      protection of IP3Rs from proteolysis. Thus, Bok may govern IP3R cleavage and
      activity during apoptosis. 

PMID- 23884413
TI  - Intracellular domain fragment of CD44 alters CD44 function in chondrocytes.
AB  - The hyaluronan receptor CD44 undergoes sequential proteolytic cleavage at the
      cell surface. The initial cleavage of the CD44 extracellular domain is followed
      by a second intramembranous cleavage of the residual CD44 fragment, liberating
      the C-terminal cytoplasmic tail of CD44. In this study conditions that promote
      CD44 cleavage resulted in a diminished capacity to assemble and retain
      pericellular matrices even though sufficient non-degraded full-length CD44
      remained. Using stable and transient overexpression of the cytoplasmic domain of
      CD44, we determined that the intracellular domain interfered with anchoring of
      the full-length CD44 to the cytoskeleton and disrupted the ability of the cells
      to bind hyaluronan and assemble a pericellular matrix. Co-immunoprecipitation
      assays were used to determine whether the mechanism of this interference was due
      to competition with actin adaptor proteins. CD44 of control chondrocytes was
      found to interact and co-immunoprecipitate with both the 65- and 130-kDa isoforms
      of ankyrin-3. Moreover, this interaction with ankyrin-3 proteins was diminished
      in cells overexpressing the CD44 intracellular domain. Mutating the putative
      ankyrin binding site of the transiently transfected CD44 intracellular domain
      diminished the inhibitory effects of this protein on matrix retention. Although
      CD44 in other cells types has been shown to interact with members of the
      ezrin/radixin/moesin (ERM) family of adaptor proteins, only modest interactions
      between CD44 and moesin could be demonstrated in chondrocytes. The data suggest
      that release of the CD44 intracellular domain into the cytoplasm of cells such as
      chondrocytes exerts a competitive or dominant-negative effect on the function of
      full-length CD44. 

PMID- 23884414
TI  - Extracellular zinc ion regulates transient receptor potential melastatin 5
      (TRPM5) channel activation through its interaction with a pore loop domain.
AB  - The transient receptor potential melastatin 5 (TRPM5) channel is a monovalent
      cation channel activated by intracellular Ca(2+). Expression of this channel is
      restricted to taste cells, the pancreas and brainstem, and is thought to be
      involved in controlling membrane potentials. Its endogenous ligands are not well
      characterized. Here, we show that extracellular application of Zn(2+) inhibits
      TRPM5 activity. In whole-cell patch-clamp recordings, extracellular application
      of ZnCl2 inhibited step-pulse-induced TRPM5 currents with 500 nM free
      intracellular Ca(2+) in a dose-dependent manner (IC50 = 4.3 MUM at -80 mV). ZnSO4
      also inhibited TRPM5 activity. Extracellular application of ZnCl2 inhibited TRPM5
      activation at several temperatures. Furthermore, inhibition by 30 MUM ZnCl2 was
      impaired in TRPM5 mutants in which His at 896, and Glu at 926 and/or Glu at 939
      in the outer pore loop were replaced with Gln. From these results, we conclude
      that extracellular Zn(2+) inhibits TRPM5 channels, and the residues in the outer
      pore loop of TRPM5 are critically involved in the inhibition.

PMID- 23884415
TI  - Notch signaling in osteocytes differentially regulates cancellous and cortical
      bone remodeling.
AB  - Notch receptors play a role in skeletal development and homeostasis, and Notch
      activation in undifferentiated and mature osteoblasts causes osteopenia. In
      contrast, Notch activation in osteocytes increases bone mass, but the mechanisms
      involved and exact functions of Notch are not known. In this study, Notch1 and -2
      were inactivated preferentially in osteocytes by mating Notch1/2 conditional
      mice, where Notch alleles are flanked by loxP sequences, with transgenics
      expressing Cre directed by the Dmp1 (dentin matrix protein 1) promoter. Notch1/2
      conditional null male and female mice exhibited an increase in trabecular bone
      volume due to an increase in osteoblasts and decrease in osteoclasts. In male
      null mice, this was followed by an increase in osteoclast number and
      normalization of bone volume. To activate Notch preferentially in osteocytes,
      Dmp1-Cre transgenics were crossed with Rosa(Notch) mice, where a loxP-flanked
      STOP cassette is placed between the Rosa26 promoter and Notch1 intracellular
      domain sequences. Dmp1-Cre(+/-);Rosa(Notch) mice exhibited an increase in
      trabecular bone volume due to decreased bone resorption and an increase in
      cortical bone due to increased bone formation. Biomechanical and chemical
      properties were not affected. Osteoprotegerin mRNA was increased, sclerostin and
      dickkopf1 mRNA were decreased, and Wnt signaling was enhanced in Dmp1-Cre(+/
      );Rosa(Notch) femurs. Botulinum toxin A-induced muscle paralysis caused
      pronounced osteopenia in control mice, but bone mass was preserved in mice
      harboring the Notch activation in osteocytes. In conclusion, Notch plays a unique
      role in osteocytes, up-regulates osteoprotegerin and Wnt signaling, and
      differentially regulates trabecular and cortical bone homeostasis. 

PMID- 23884416
TI  - MicroRNA-24 suppression of N-deacetylase/N-sulfotransferase-1 (NDST1) reduces
      endothelial cell responsiveness to vascular endothelial growth factor A (VEGFA).
AB  - Heparan sulfate (HS) proteoglycans, present at the plasma membrane of vascular
      endothelial cells, bind to the angiogenic growth factor VEGFA to modulate its
      signaling through VEGFR2. The interactions between VEGFA and proteoglycan co
      receptors require sulfated domains in the HS chains. To date, it is essentially
      unknown how the formation of sulfated protein-binding domains in HS can be
      regulated by microRNAs. In the present study, we show that microRNA-24 (miR-24)
      targets NDST1 to reduce HS sulfation and thereby the binding affinity of HS for
      VEGFA. Elevated levels of miR-24 also resulted in reduced levels of VEGFR2 and
      blunted VEGFA signaling. Similarly, suppression of NDST1 using siRNA led to a
      reduction in VEGFR2 expression. Consequently, not only VEGFA binding, but also
      VEGFR2 protein expression is dependent on NDST1 function. Furthermore,
      overexpression of miR-24, or siRNA-mediated reduction of NDST1, reduced
      endothelial cell chemotaxis in response to VEGFA. These findings establish NDST1
      as a target of miR-24 and demonstrate how such NDST1 suppression in endothelial
      cells results in reduced responsiveness to VEGFA. 

PMID- 23884417
TI  - A3 domain region 1803-1818 contributes to the stability of activated factor VIII
      and includes a binding site for activated factor IX.
AB  - A recent chemical footprinting study in our laboratory suggested that region 1803
      1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa).
      This site has also been implicated to interact with activated factor IX (FIXa).
      Asn-1810 further comprises an N-linked glycan, which seems incompatible with a
      role of the amino acids 1803-1818 for FIXa or A2 domain binding. In the present
      study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C
      variant, and two FVIII variants in which residues 1803-1810 and 1811-1818 are
      replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies
      showed that only FVIII/FV 1811-1818 has a decreased apparent binding affinity for
      FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired
      complex formation with only FVIII/FV 1811-1818 on lipospheres. Site-directed
      mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To
      evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and
      the decline in cofactor function was followed over time. FVIII/FV 1803-1810 and
      FVIII/FV 1811-1818 but not FVIII-N1810C showed a decreased FVIIIa half-life.
      However, when the FVIII variants were activated in presence of FIXa, only
      FVIII/FV 1811-1818 demonstrated an enhanced decline in cofactor function. Surface
      plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A,
      E1811A, and F1816A exhibit enhanced dissociation after activation. The results
      together demonstrate that the glycan at 1810 is not involved in FVIII cofactor
      function, and that Phe-1816 of region 1811-1818 contributes to FIXa binding. Both
      regions 1803-1810 and 1811-1818 contribute to FVIIIa stability. 

PMID- 23884418
TI  - Sturgeon osteocalcin shares structural features with matrix Gla protein:
      evolutionary relationship and functional implications.
AB  - Osteocalcin (OC) and matrix Gla protein (MGP) are considered evolutionarily
      related because they share key structural features, although they have been
      described to exert different functions. In this work, we report the
      identification and characterization of both OC and MGP from the Adriatic
      sturgeon, a ray-finned fish characterized by a slow evolution and the retention
      of many ancestral features. Sturgeon MGP shows a primary structure, post
      translation modifications, and patterns of mRNA/protein distribution and
      accumulation typical of known MGPs, and it contains seven possible Gla residues
      that would make the sturgeon protein the most gamma-carboxylated among known
      MGPs. In contrast, sturgeon OC was found to present a hybrid structure. Indeed,
      although exhibiting protein domains typical of known OCs, it also contains
      structural features usually found in MGPs (e.g. a putative phosphorylated
      propeptide). Moreover, patterns of OC gene expression and protein accumulation
      overlap with those reported for MGP; OC was detected in bone cells and
      mineralized structures but also in soft and cartilaginous tissues. We propose
      that, in a context of a reduced rate of evolution, sturgeon OC has retained
      structural features of the ancestral protein that emerged millions of years ago
      from the duplication of an ancient MGP gene and may exhibit intermediate
      functional features. 

PMID- 23884419
TI  - Ganglioside GM1-mediated transcytosis of cholera toxin bypasses the retrograde
      pathway and depends on the structure of the ceramide domain.
AB  - Cholera toxin causes diarrheal disease by binding ganglioside GM1 on the apical
      membrane of polarized intestinal epithelial cells and trafficking retrograde
      through sorting endosomes, the trans-Golgi network (TGN), and into the
      endoplasmic reticulum. A fraction of toxin also moves from endosomes across the
      cell to the basolateral plasma membrane by transcytosis, thus breeching the
      intestinal barrier. Here we find that sorting of cholera toxin into this
      transcytotic pathway bypasses retrograde transport to the TGN. We also find that
      GM1 sphingolipids can traffic from apical to basolateral membranes by
      transcytosis in the absence of toxin binding but only if the GM1 species contain
      cis-unsaturated or short acyl chains in the ceramide domain. We found previously
      that the same GM1 species are needed to efficiently traffic retrograde into the
      TGN and endoplasmic reticulum and into the recycling endosome, implicating a
      shared mechanism of action for sorting by lipid shape among these pathways. 

PMID- 23884420
TI  - Essential role for vacuolar acidification in Candida albicans virulence.
AB  - Fungal infections are on the rise, with mortality above 30% in patients with
      septic Candida infections. Mutants lacking V-ATPase activity are avirulent and
      fail to acidify endomembrane compartments, exhibiting pleiotropic defects in
      secretory, endosomal, and vacuolar pathways. However, the individual contribution
      of organellar acidification to virulence and its associated traits is not known.
      To dissect their separate roles in Candida albicans pathogenicity we generated
      knock-out strains for the V0 subunit a genes VPH1 and STV1, which target the
      vacuole and secretory pathway, respectively. While the two subunits were
      redundant in many vma phenotypes, such as alkaline pH sensitivity, calcium
      homeostasis, respiratory defects, and cell wall integrity, we observed a unique
      contribution of VPH1. Specifically, vph1Delta was defective in acidification of
      the vacuole and its dependent functions, such as metal ion sequestration as
      evidenced by hypersensitivity to Zn(2+) toxicity, whereas stv1Delta resembled
      wild type. In growth conditions that elicit morphogenic switching, vph1Delta was
      defective in forming hyphae whereas stv1Delta was normal or only modestly
      impaired. Host cell interactions were evaluated in vitro using the Caco-2 model
      of intestinal epithelial cells, and murine macrophages. Like wild type, stv1Delta
      was able to inflict cellular damage in Caco-2 and macrophage cells, as assayed by
      LDH release, and escape by filamentation. In contrast, vph1Delta resembled a
      vma7Delta mutant, with significant attenuation in host cell damage. Finally, we
      show that VPH1 is required for fungal virulence in a murine model of systemic
      infection. Our results suggest that vacuolar acidification has an essential
      function in the ability of C. albicans to form hyphae and establish infection. 

PMID- 23884421
TI  - Restoration of glutamatergic transmission by dopamine D4 receptors in stressed
      animals.
AB  - The prefrontal cortex (PFC), a key brain region for cognitive and emotional
      processes, is highly regulated by dopaminergic inputs. The dopamine D4 receptor,
      which is enriched in PFC, has been implicated in mental disorders, such as
      attention deficit-hyperactivity disorder and schizophrenia. Recently we have
      found homeostatic regulation of AMPA receptor-mediated synaptic transmission in
      PFC pyramidal neurons by the D4 receptor, providing a potential mechanism for D4
      in stabilizing cortical excitability. Because stress is tightly linked to
      adaptive and maladaptive changes associated with mental health and disorders, we
      examined the synaptic actions of D4 in stressed rats. We found that neural
      excitability was elevated by acute stress and dampened by repeated stress. D4
      activation produced a potent reduction of excitatory transmission in acutely
      stressed animals and a marked increase of excitatory transmission in repeatedly
      stressed animals. These effects of D4 targeted GluA2-lacking AMPA receptors and
      relied on the bi-directional regulation of calcium/calmodulin kinase II activity.
      The restoration of PFC glutamatergic transmission in stress conditions may enable
      D4 receptors to serve as a synaptic stabilizer in normal and pathological
      conditions. 

PMID- 23884422
TI  - Roles of phosphate recognition in inositol 1,3,4,5,6-pentakisphosphate 2-kinase
      (IPK1) substrate binding and activation.
AB  - Inositol phosphate kinases (IPKs) sequentially phosphorylate inositol phosphates
      (IPs) to yield a group of small signaling molecules involved in diverse cellular
      processes. IPK1 (inositol 1,3,4,5,6-pentakisphosphate 2-kinase) phosphorylates
      inositol 1,3,4,5,6-pentakisphosphate to inositol 1,2,3,4,5,6-hexakisphosphate;
      however, the mechanism of IP recognition employed by IPK1 is currently
      unresolved. We demonstrated previously that IPK1 possesses an unstable N-terminal
      lobe in the absence of IP, which led us to propose that the phosphate profile of
      the IP was linked to stabilization of IPK1. Here, we describe a systematic study
      to determine the roles of the 1-, 3-, 5-, and 6-phosphate groups of inositol
      1,3,4,5,6-pentakisphosphate in IP binding and IPK1 activation. The 5- and 6
      phosphate groups were the most important for IP binding to IPK1, and the 1- and 3
      phosphate groups were more important for IPK1 activation than the others.
      Moreover, we demonstrate that there are three critical residues (Arg-130, Lys
      170, and Lys-411) necessary for IPK1 activity. Arg-130 is the only substrate
      binding N-terminal lobe residue that can render IPK1 inactive; its 1-phosphate is
      critical for full IPK1 activity and for stabilization of the active conformation
      of IPK1. Taken together, our results support the model for recognition of the IP
      substrate by IPK1 in which (i) the 4-, 5-, and 6-phosphates are initially
      recognized by the C-terminal lobe, and subsequently, (ii) the interaction between
      the 1-phosphate and Arg-130 stabilizes the N-terminal lobe and activates IPK1.
      This model of IP recognition, believed to be unique among IPKs, could be
      exploited for selective inhibition of IPK1 in future studies that investigate the
      role of higher IPs. 

PMID- 23884423
TI  - Ribosomal RNA gene transcription mediated by the master genome regulator protein
      CCCTC-binding factor (CTCF) is negatively regulated by the condensin complex.
AB  - CCCTC-binding factor (CTCF) is a ubiquitously expressed "master weaver" and plays
      multiple functions in the genome, including transcriptional
      activation/repression, chromatin insulation, imprinting, X chromosome
      inactivation, and high-order chromatin organization. It has been shown that CTCF
      facilitates the recruitment of the upstream binding factor onto ribosomal DNA
      (rDNA) and regulates the local epigenetic state of rDNA repeats. However, the
      mechanism by which CTCF modulates rRNA gene transcription has not been well
      understood. Here we found that wild-type CTCF augments the pre-rRNA level, cell
      size, and cell growth in cervical cancer cells. In contrast, RNA interference
      mediated knockdown of CTCF reduced pre-rRNA transcription. CTCF positively
      regulates rRNA gene transcription in a RNA polymerase I-dependent manner. We
      identified an RRGR motif as a putative nucleolar localization sequence in the C
      terminal region of CTCF that is required for activating rRNA gene transcription.
      Using mass spectrometry, we identified SMC2 and SMC4, two subunits of condensin
      complexes that interact with CTCF. Condensin negatively regulates CTCF-mediated
      rRNA gene transcription. Knockdown of SMC2 expression significantly facilitates
      the loading of CTCF and the upstream binding factor onto the rDNA locus and
      increases histone acetylation across the rDNA locus. Taken together, our study
      suggests that condensin competes with CTCF in binding to a specific rDNA locus
      and negatively regulates CTCF-mediated rRNA gene transcription. 

PMID- 23884425
TI  - [Reduced vigilance and anisocoria following subdural hematoma].

PMID- 23884424
TI  - Induction of a tumor-associated activating mutation in protein tyrosine
      phosphatase Ptpn11 (Shp2) enhances mitochondrial metabolism, leading to oxidative
      stress and senescence.
AB  - Activating mutations in Ptpn11 (Shp2), a protein tyrosine phosphatase involved in
      diverse cell signaling pathways, are associated with pediatric leukemias and
      solid tumors. However, the pathogenic effects of these mutations have not been
      fully characterized. Here, we report that induction of the Ptpn11(E76K/+)
      mutation, the most common and active Ptpn11 mutation found in leukemias and solid
      tumors, in primary mouse embryonic fibroblasts resulted in proliferative arrest
      and premature senescence. As a result, apoptosis was markedly increased. These
      cellular responses were accompanied and mediated by up-regulation of p53 and p21.
      Moreover, intracellular levels of reactive oxygen species (ROS), byproducts of
      mitochondrial oxidative phosphorylation, were elevated in Ptpn11(E76K/+) cells.
      Since Shp2 is also distributed to the mitochondria (in addition to the cytosol),
      the impact of the Ptpn11(E76K/+) mutation on mitochondrial function was analyzed.
      These analyses revealed that oxygen consumption of Ptpn11(E76K/+) cells and the
      respiratory function of Ptpn11(E76K/+) mitochondria were significantly increased.
      Furthermore, we found that phosphorylation of mitochondrial Stat3, one of the
      substrates of Shp2 phosphatase, was greatly decreased in the mutant cells with
      the activating mutation Ptpn11(E76K/+). This study provides novel insights into
      the initial effects of tumor-associated Ptpn11 mutations. 

PMID- 23884426
TI  - Nickel(II) in chelate N2O2 environment. DFT approach and in-depth molecular
      orbital and configurational analysis.
AB  - The O-N-N-O-type tetradentate ligands H2S,S-eddp (H2S,S-eddp stands for S,S
      ethylenediamine-N,N'-di-2-propionic acid) and H2edap (H2edap stands for
      ethylenediamine-N-acetic-N'-3-propionic acid) and the corresponding novel
      octahedral nickel(II) complexes have been prepared and characterized. N2O2
      ligands coordinate to the nickel(II) ion via four donor atoms (two deprotonated
      carboxylate atoms and two amine nitrogens) affording octahedral geometry in the
      case of all investigated Ni(II) complexes. A six coordinate, octahedral geometry
      has been verified crystallographically for the s-cis-[Ni(S,S-eddp)(H2O)2]
      complex. Structural data correlating similarly chelated Ni(II) complexes have
      been used to carry out an extensive configuration analysis. Molecular mechanics
      and Density Functional Theory (DFT) have been used to model the most stable
      geometric isomer, yielding, at the same time, significant structural and
      spectroscopic (TDDFT) data. The results from density functional studies have been
      compared to X-ray data. Natural Bond Orbital (NBO) and Natural Energetic
      Decomposition Analysis (NEDA) have been done for the [Ni(edda-type)(H2O)(2-n)]
      and nH2O fragments. Molecular orbital analysis (MPA) is given as well. The infra
      red and electronic absorption spectra of the complexes are discussed in
      comparison to the related complexes of known geometries.

PMID- 23884427
TI  - Human telomerase reverse transcriptase regulates MMP expression independently of
      telomerase activity via NF-kappaB-dependent transcription.
AB  - Telomerase plays a pivotal role in the pathology of aging and cancer by
      controlling telomere length and integrity. However, accumulating evidence
      indicates that telomerase reverse transcriptase may have fundamental biological
      functions independent of its enzymatic activity in telomere maintenance. In this
      study, the ectopic expression of human telomerase reverse transcriptase (hTERT)
      and its catalytic mutant hTERT K626A induced cancer cell invasion accompanied by
      the up-regulation of the metalloproteinases (MMPs) MMP1, -3, -9, and -10. Both
      hTERT and hTERT K626A induced MMP9 mRNA expression and promoter activity in an NF
      kappaB-dependent manner. hTERT and hTERT K626A also regulated the expression of
      several NF-kappaB target genes in cancer cell lines. Furthermore, both hTERT and
      hTERT K626A interacted with NF-kappaB p65 and increased NF-kappaB p65 nuclear
      accumulation and DNA binding. A mammalian 1-hybrid assay showed a functional
      interplay between hTERT and NF-kappaB p65 that may mediate NF-kappaB-dependent
      transcription activation in cells. Together, these data reveal a telomere
      independent role for telomerase as a transcriptional modulator of the NF-kappaB
      signaling pathway and a possible contributor to cancer development and
      progression.

PMID- 23884429
TI  - Silver cations fold i-motif at neutral pH.
AB  - i-Motif DNA structures have previously been utilised for many different
      nanotechnological applications, but all have used acidic conditions to fold the
      DNA. Herein we describe the use of silver cations to fold an i-motif forming DNA
      sequence at physiological pH. Subsequent DNA unfolding can be achieved by
      chelation with cysteine. 

PMID- 23884428
TI  - Targeting prostate cancer cell lines with polo-like kinase 1 inhibitors as a
      single agent and in combination with histone deacetylase inhibitors.
AB  - Combinations of anticancer therapies with high efficacy and low toxicities are
      highly sought after. Therefore, we studied the effect of polo-like kinase 1
      (Plk1) inhibitors on prostate cancer cells as a single agent and in combination
      with histone deacetylase (HDAC) inhibitors valproic acid and vorinostat. IC50s of
      Plk1 inhibitors BI 2536 and BI 6727 were determined in prostate cancer cells by
      MTS assays. Morphological and molecular changes were assessed by immunoblotting,
      immunofluorescence, flow cytometry, real-time RT-PCR, and pulldown assays.
      Efficacy of combination therapy was assessed by MTS and clonogenic assays. IC50
      values in DU145, LNCaP, and PC3 cells were 50, 75, and 175 nM, respectively, for
      BI 2536 and 2.5, 5, and 600 nM, respectively, for BI 6727. Human prostate
      fibroblasts and normal prostate epithelial cells were unaffected at these
      concentrations. While DU145 and LNCaP cells were solely arrested in mitosis on
      treatment, PC3 cells accumulated in G2 phase and mitosis, suggesting a weak
      spindle assembly checkpoint. Combining Plk1 inhibitors with HDAC inhibitors had
      synergistic antitumor effects in vitro. DMSO-treated prostate cancer cells were
      used as controls to study the effect of Plk1 and HDAC inhibition. Plk1 inhibitors
      decreased proliferation and clonogenic potential of prostate cancer cells. Hence,
      Plk1 may serve as an important molecular target for inhibiting prostate cancer.
      Combining HDAC inhibitors with BI 2536 or BI 6727 may be an effective treatment
      strategy against prostate cancer.

PMID- 23884430
TI  - Synthesis of alkylcarbonate analogs of O-acetyl-ADP-ribose.
AB  - The non-hydrolyzable alkylcarbonate analogs of O-acetyl-ADP-ribose have been
      synthesized from the phosphorylated ribose derivatives after coupling with AMP
      morpholidate promoted by mechanical grinding. The analogs were assessed for their
      ability to inhibit the human sirtuin homolog SIRT1. 

PMID- 23884431
TI  - Maternal smoking during pregnancy and offspring conduct problems: evidence from 3
      independent genetically sensitive research designs.
AB  - IMPORTANCE: Several studies report an association between maternal smoking during
      pregnancy and offspring conduct disorder. However, past research evidences
      difficulty in disaggregating prenatal environmental influences from genetic and
      postnatal environmental influences. OBJECTIVE: To examine the relationship
      between maternal smoking during pregnancy and offspring conduct problems among
      children reared by genetically related mothers and genetically unrelated mothers.
      DESIGN, SETTING, AND PARTICIPANTS: The following 3 studies using distinct but
      complementary research designs were used: The Christchurch Health and Development
      Study (a longitudinal cohort study that includes biological and adopted
      children), the Early Growth and Development Study (a longitudinal adoption-at
      birth study), and the Cardiff IVF (In Vitro Fertilization) Study (an adoption-at
      conception study among genetically related families and genetically unrelated
      families). Maternal smoking during pregnancy was measured as the mean number of
      cigarettes per day (0, 1-9, or 10) smoked during pregnancy. Possible covariates
      were controlled for in the analyses, including child sex, birth weight,
      race/ethnicity, placement age, and breastfeeding, as well as maternal education
      and maternal age at birth and family breakdown, parenting practices, and family
      socioeconomic status. MAIN OUTCOMES AND MEASURE: Offspring conduct problems (age
      range, 4-10 years) reported by parents or teachers using the behavior rating
      scales by Rutter and Conners, the Child Behavior Checklist and the Children's
      Behavior Questionnaire Short Form, and the Strengths and Difficulties
      Questionnaire. RESULTS: A significant association between maternal smoking during
      pregnancy and offspring conduct problems was observed among children reared by
      genetically related mothers and genetically unrelated mothers. Results from a
      meta-analysis affirmed this pattern of findings across pooled study samples.
      CONCLUSIONS AND RELEVANCE: Findings across 3 studies using a complement of
      genetically sensitive research designs suggest that smoking during pregnancy is a
      prenatal risk factor for offspring conduct problems when controlling for specific
      perinatal and postnatal confounding factors.

PMID- 23884432
TI  - Signaling efficiency of Galphaq through its effectors p63RhoGEF and GEFT depends
      on their subcellular location.
AB  - The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of
      the Dbl family of guanine nucleotide exchange factors. These proteins can be
      activated by the heterotrimeric G-protein subunit Galphaq. We show that p63RhoGEF
      is located at the plasma membrane, whereas GEFT is confined to the cytoplasm.
      Live-cell imaging studies yielded quantitative information on diffusion
      coefficients, association rates and encounter times of GEFT and p63RhoGEF.
      Calcium signaling was examined as a measure of the signal transmission, revealing
      more efficient signaling through the membrane-associated p63RhoGEF. A rapamycin
      dependent recruitment system was used to dynamically alter the subcellular
      location and concentration of GEFT, showing efficient signaling through GEFT only
      upon membrane recruitment. Together, our results show efficient signal
      transmission through membrane located effectors, and highlight a role for
      increased concentration rather than increased encounter times due to membrane
      localization in the Galphaq mediated pathways to p63RhoGEF and PLCbeta. 

PMID- 23884433
TI  - Effect of BDNF Val66Met and serotonin transporter 5-HTTLPR polymorphisms on
      psychopathological characteristics in a sample of university students.
AB  - OBJECTIVE: The aims of this study were to evaluate the impact of the brain
      derived neurotrophic factor (BDNF) Val66Met polymorphism on several psychological
      characteristics in a group of Greek University students and to explore putative
      interactions with the serotonin-transporter-linked polymorphic region (5-HTTLPR)
      and serious past adverse experiences. METHODS: A total of 224 students were
      genotyped and classified as (a) carriers or noncarriers of the Met allele of the
      BDNF Val66Met polymorphism and (b) carriers or noncarriers of the S or Lg alleles
      (S') of the 5-HTTLPR polymorphism. Students were evaluated using a battery of
      standard psychological tests and answered questionnaires on serious past adverse
      experiences. RESULTS: The Val/Val BDNF genotype was associated with higher scores
      in several psychopathological dimensions. When the effect of the BDNF Met allele
      was examined in relation to 5-HTTLPR, it was restricted to S' noncarriers. Among
      these students, BDNF Met allele carriers had lower scores compared with
      noncarriers. The effects of the Met allele on the S' allele noncarriers in the
      anxiety and phobic anxiety dimensions were more pronounced among individuals who
      had reported no serious life adversities. CONCLUSION: There may be a protective
      role of the BDNF Met allele in several psychopathological features and it is
      suggested that some of these effects are moderated by 5-HTTLPR.

PMID- 23884434
TI  - SGO1 but not SGO2 is required for maintenance of centromere cohesion in
      Arabidopsis thaliana meiosis.
AB  - Shugoshin is a protein conserved in eukaryotes and protects sister chromatid
      cohesion at centromeres in meiosis. In our study, we identified the homologs of
      SGO1 and SGO2 in Arabidopsis thaliana. We show that AtSGO1 is necessary for the
      maintenance of centromere cohesion in meiosis I since atsgo1 mutants display
      premature separation of sister chromatids starting from anaphase I. Furthermore,
      we show that the localization of the specific centromeric cohesin AtSYN1 is not
      affected in atsgo1, suggesting that SGO1 centromere cohesion maintenance is not
      mediated by protection of SYN1 from cleavage. Finally, we show that AtSGO2 is
      dispensable for both meiotic and mitotic cell progression in Arabidopsis. 

PMID- 23884435
TI  - [Abductor digiti minimi muscle flap for defect coverage of the hand].
AB  - OBJECTIVE: Defect coverage of the ulnar aspect of the hand, wrist and hypothenar
      with an abductor digiti minimi muscle flap and split skin graft. INDICATIONS:
      Soft tissue defects of the ulnar aspect of the hand, wrist and hypothenar.
      Osteomyelitis of the fifth metacarpal bone. CONTRAINDICATIONS: Large defects > 3
      * 5 cm, complex hand trauma, injuries of the ulnar artery or within the area of
      the pedicle. SURGICAL TECHNIQUE: Marking of the flap's rotational radius, using
      the pisiform bone as the center point. Ulnar skin incision and exposure and
      detachment of the distal flap pole, which is located at the level of the
      metacarpophalangeal (MCP) joint. Dissection of the abductor digiti minimi muscle
      flap up to the vascular pedicle in the area of the pisiform bone. Transposition
      and fixation of the flap onto the defect after opening of the tourniquet.
      Coverage of the muscle flap with a split skin graft. Wound closure of the donor
      side. POSTOPERATIVE MANAGEMENT: Palmar cast splinting in intrinsic-plus position
      for 10 days physiotherapy. Scar care and compression glove for 3 months. RESULTS:
      In total, 9 patients showed good results with a reliable defect coverage due to a
      constant anatomy and easy preparation.

PMID- 23884436
TI  - Standardising the descriptive epidemiology of osteoporosis: recommendations from
      the Epidemiology and Quality of Life Working Group of IOF.
AB  - The Committee of Scientific Advisors of International Osteoporosis Foundation
      (IOF) recommends that papers describing the descriptive epidemiology of
      osteoporosis using bone mineral density (BMD) at the femoral neck include T
      scores derived from an international reference standard. INTRODUCTION: The
      prevalence of osteoporosis as defined by the T-score is inconsistently reported
      in the literature which makes comparisons between studies problematic. METHODS:
      The Epidemiology and Quality of Life Working Group of IOF convened to make its
      recommendations and endorsement sought thereafter from the Committee of
      Scientific Advisors of IOF. RESULTS: The Committee of Scientific Advisors of IOF
      recommends that papers describing the descriptive epidemiology of osteoporosis
      using BMD at the femoral neck include T-scores derived from the National Health
      and Nutrition Examination Survey III reference database for femoral neck
      measurements in Caucasian women aged 20-29 years. CONCLUSIONS: It is expected
      that the use of the reference standard will help resolve difficulties in the
      comparison of results between studies and the comparative assessment of new
      technologies.

PMID- 23884437
TI  - Disease-specific perception of fracture risk and incident fracture rates: GLOW
      cohort study.
AB  - Accurate patient risk perception of adverse health events promotes greater
      autonomy over, and motivation towards, health-related lifestyles. INTRODUCTION:
      We compared self-perceived fracture risk and 3-year incident fracture rates in
      postmenopausal women with a range of morbidities in the Global Longitudinal study
      of Osteoporosis in Women (GLOW). METHODS: GLOW is an international cohort study
      involving 723 physician practices across ten countries (Europe, North America,
      Australasia); 60,393 women aged >=55 years completed baseline questionnaires
      detailing medical history and self-perceived fracture risk. Annual follow-up
      determined self-reported incident fractures. RESULTS: In total 2,945/43,832
      (6.8%) sustained an incident fracture over 3 years. All morbidities were
      associated with increased fracture rates, particularly Parkinson's disease
      (hazard ratio [HR]; 95% confidence interval [CI], 3.89; 2.78-5.44), multiple
      sclerosis (2.70; 1.90-3.83), cerebrovascular events (2.02; 1.67-2.46), and
      rheumatoid arthritis (2.15; 1.53-3.04) (all p < 0.001). Most individuals
      perceived their fracture risk as similar to (46%) or lower than (36%) women of
      the same age. While increased self-perceived fracture risk was strongly
      associated with incident fracture rates, only 29% experiencing a fracture
      perceived their risk as increased. Under-appreciation of fracture risk occurred
      for all morbidities, including neurological disease, where women with low self
      perceived fracture risk had a fracture HR 2.39 (CI 1.74-3.29) compared with women
      without morbidities. CONCLUSIONS: Postmenopausal women with morbidities tend to
      under-appreciate their risk, including in the context of neurological diseases,
      where fracture rates were highest in this cohort. This has important implications
      for health education, particularly among women with Parkinson's disease, multiple
      sclerosis, or cerebrovascular disease.

PMID- 23884438
TI  - Involvement of JNK in the embryonic development and organogenesis in zebrafish.
AB  - c-Jun N-terminal kinase (JNK) is one of the mitogen-activated protein kinases.
      Previous studies showed that the JNK is involved in signaling pathways initiating
      cell cycle, and eventually, causing apoptosis through persistent activation in
      mammals. In this article, it is further revealed that the jnk1 gene is closely
      related with the embryonic development and organogenesis in zebrafish. RT-PCR and
      Western blot analysis show that there were distinct expression patterns of JNK at
      the different developmental stages as well as in the various tissues in
      zebrafish. Knockdown of jnk1 by RNA interference (RNAi) resulted in high lethal,
      serious retardation and malformations of embryos in zebrafish. SP600125, a JNK
      specific inhibitor, gives rise to high mortality in zebrafish, similar to that
      caused by the jnk1 RNA interference. SP600125 is also responsible for the severe
      abnormality of organs, especially the skeletal system, such as skull, mandible
      deficiency, and cyrtosis heterauxesis. The results also indicate that the
      inhibition of JNK by SP600125 suppresses the ovarian differentiation during the
      embryo development in zebrafish. Overall, our study demonstrates that the jnk1
      gene is required for ovary differentiation and development in the zebrafish, and
      down-regulated JNK directly inhibits ovary differentiation during early
      ontogenetic stages. 

PMID- 23884439
TI  - Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of
      patients with advanced gastric cancer: correlative study in Japan Clinical
      Oncology Group Trial JCOG9912.
AB  - BACKGROUND: Since the best chemotherapy regimen for each patient with advanced
      gastric cancer is uncertain, we aimed to identify molecular prognostic or
      predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III
      trial for advanced gastric cancer. PATIENTS AND METHODS: Endoscopic biopsy
      specimens from primary lesions were collected in 445 of 704 randomized patients
      in JCOG9912. We measured the mRNA expression of excision repair cross
      complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine
      dehydrogenase, and five other genes, then, categorized them into low and high
      groups relative to the median, and examined whether gene expression was
      associated with efficacy end point. RESULTS: Multivariate analyses showed that
      high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08-1.75; P =
      0.010], performance status >= 1 (HR 1.45; 95% CI 1.13-1.86; P = 0.004), and
      number of metastatic sites >= 2 (HR 1.66; 95% CI 1.28-1.86; P < 0.001) were
      associated with a poor prognosis, and recurrent disease (versus unresectable; HR
      0.75; 95% CI 0.56-1.00; P = 0.049) was associated with a favorable prognosis.
      None of these molecular factors were a predictive marker for choosing irinotecan
      plus cisplatin or 5-fluorouracil rather than S-1. CONCLUSION: These correlative
      analyses suggest that ERCC1 is an independent prognostic factor for overall
      survival in the first-line treatment of gastric cancer. CLINICAL TRIAL NUMBER:
      C000000062, www.umin.ac.jp.

PMID- 23884440
TI  - Family history of cancer and the risk of cancer: a network of case-control
      studies.
AB  - BACKGROUND: The risk of many cancers is higher in subjects with a family history
      (FH) of cancer at a concordant site. However, few studies investigated FH of
      cancer at discordant sites. PATIENTS AND METHODS: This study is based on a
      network of Italian and Swiss case-control studies on 13 cancer sites conducted
      between 1991 and 2009, and including more than 12 000 cases and 11 000 controls.
      We collected information on history of any cancer in first degree relatives, and
      age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic
      regression models, adjusted for major confounding factors. RESULTS: All sites
      showed an excess risk in relation to FH of cancer at the same site. Increased
      risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer
      (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1),
      breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic
      cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and
      prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the
      association with FH was stronger when the proband was affected at age <60 years.
      CONCLUSIONS: Our results point to several potential cancer syndromes that appear
      among close relatives and may indicate the presence of genetic factors
      influencing multiple cancer sites.

PMID- 23884441
TI  - Nickel nanoparticle chains inside carbonized polymer nanofibers: preparation by
      electrospinning and ion-beam irradiation.
AB  - Novel organic-inorganic composite 1D nanostructures composed of carbonized
      conductive nanofibers and nickel nanoparticle chains were prepared by the
      combination of an electrospinning method from metal complex-containing polymer
      solutions and an ion-beam irradiation technique. The nickel nanoparticle chains
      were formed by self-assembly inside the carbonized nanofibers, which were
      characterized by STEM-HAADF observation and XPS spectroscopy. The existence of
      nickel complexes and the subsequent formation of nickel nanoparticles enhanced
      the electrical conductivities of carbonized nanofibers to reach above 0.5 S cm(
      1) for the 6FDA-6FAP nanofibrous membrane containing 5.0 wt% Ni(acac)2 after ion
      beam irradiation at an ion fluence of 1 * 10(16) ions per cm(2). 

PMID- 23884442
TI  - A non-canonical role for the C. elegans dosage compensation complex in growth and
      metabolic regulation downstream of TOR complex 2.
AB  - The target of rapamycin complex 2 (TORC2) pathway is evolutionarily conserved and
      regulates cellular energetics, growth and metabolism. Loss of function of the
      essential TORC2 subunit Rictor (RICT-1) in Caenorhabditis elegans results in slow
      developmental rate, reduced brood size, small body size, increased fat mass and
      truncated lifespan. We performed a rict-1 suppressor RNAi screen of genes
      encoding proteins that possess the phosphorylation sequence of the AGC family
      kinase SGK, a key downstream effector of TORC2. Only RNAi to dpy-21 suppressed
      rict-1 slow developmental rate. DPY-21 functions canonically in the ten-protein
      dosage compensation complex (DCC) to downregulate the expression of X-linked
      genes only in hermaphroditic worms. However, we find that dpy-21 functions
      outside of its canonical role, as RNAi to dpy-21 suppresses TORC2 mutant
      developmental delay in rict-1 males and hermaphrodites. RNAi to dpy-21 normalized
      brood size and fat storage phenotypes in rict-1 mutants, but failed to restore
      normal body size and normal lifespan. Further dissection of the DCC via RNAi
      revealed that other complex members phenocopy the dpy-21 suppression of rict-1,
      as did RNAi to the DCC effectors set-1 and set-4, which methylate histone 4 on
      lysine 20 (H4K20). TORC2/rict-1 animals show dysregulation of H4K20 mono- and tri
      methyl silencing epigenetic marks, evidence of altered DCC, SET-1 and SET-4
      activity. DPY-21 protein physically interacts with the protein kinase SGK-1,
      suggesting that TORC2 directly regulates the DCC. Together, the data suggest non
      canonical, negative regulation of growth and reproduction by DPY-21 via DCC, SET
      1 and SET-4 downstream of TORC2 in C. elegans. 

PMID- 23884443
TI  - The insulator protein Suppressor of Hairy-wing is an essential transcriptional
      repressor in the Drosophila ovary.
AB  - Suppressor of Hairy-wing [Su(Hw)] is a DNA-binding factor required for gypsy
      insulator function and female germline development in Drosophila. The insulator
      function of the gypsy retrotransposon depends on Su(Hw) binding to clustered
      Su(Hw) binding sites (SBSs) and recruitment of the insulator proteins Centrosomal
      Protein 190 kD (CP190) and Modifier of mdg4 67.2 kD (Mod67.2). By contrast, the
      Su(Hw) germline function involves binding to non-clustered SBSs and does not
      require CP190 or Mod67.2. Here, we identify Su(Hw) target genes, using genome
      wide analyses in the ovary to uncover genes with an ovary-bound SBS that are
      misregulated upon Su(Hw) loss. Most Su(Hw) target genes demonstrate enriched
      expression in the wild-type CNS. Loss of Su(Hw) leads to increased expression of
      these CNS-enriched target genes in the ovary and other tissues, suggesting that
      Su(Hw) is a repressor of neural genes in non-neural tissues. Among the Su(Hw)
      target genes is RNA-binding protein 9 (Rbp9), a member of the ELAV/Hu gene
      family. Su(Hw) regulation of Rbp9 appears to be insulator independent, as Rbp9
      expression is unchanged in a genetic background that compromises the functions of
      the CP190 and Mod67.2 insulator proteins, even though both localize to Rbp9 SBSs.
      Rbp9 misregulation is central to su(Hw)(-/-) sterility, as Rbp9(+/-), su(Hw)(-/-)
      females are fertile. Eggs produced by Rbp9(+/-), su(Hw)(-/-) females show
      patterning defects, revealing a somatic requirement for Su(Hw) in the ovary. Our
      studies demonstrate that Su(Hw) is a versatile transcriptional regulatory protein
      with an essential developmental function involving transcriptional repression. 

PMID- 23884444
TI  - The polyubiquitin gene Ubi-p63E is essential for male meiotic cell cycle
      progression and germ cell differentiation in Drosophila.
AB  - The ubiquitin proteasome system (UPS) regulates many biological pathways by post
      translationally ubiquitylating proteins for degradation. Although maintaining a
      dynamic balance between free ubiquitin and ubiquitylated proteins is key to UPS
      function, the mechanisms that regulate ubiquitin homeostasis in different tissues
      through development are not clear. Here we show, via analysis of the magellan
      (magn) complementation group, that loss of function of the Drosophila
      polyubiquitin Ubi-p63E results specifically in meiotic arrest sterility in males.
      Ubi-p63E contributes predominantly to maintaining the free ubiquitin pool in
      testes. The function of Ubi-p63E is required cell-autonomously for proper meiotic
      chromatin condensation, cell cycle progression and spermatid differentiation.
      magn mutant germ cells develop normally to the spermatocyte stage but arrest at
      the G2/M transition of meiosis I, with lack of protein expression of the key
      meiotic cell cycle regulators Boule and Cyclin B. Loss of Ubi-p63E function did
      not strongly affect the spermatocyte transcription program regulated by the
      testis TBP-associated factor (tTAF) or meiosis arrest complex (tMAC) genes.
      Knocking down proteasome function specifically in spermatocytes caused a
      different meiotic arrest phenotype, suggesting that the magn phenotype might not
      result from general defects in protein degradation. Our results suggest a
      conserved role of polyubiquitin genes in male meiosis and a potential mechanism
      leading to meiosis I maturation arrest. 

PMID- 23884445
TI  - Gpr177 regulates pulmonary vasculature development.
AB  - Establishment of the functional pulmonary vasculature requires intimate
      interaction between the epithelium and mesenchyme. Previous genetic studies have
      led to inconsistent conclusions about the contribution of epithelial Wnts to
      pulmonary vasculature development. This discrepancy is possibly due to the
      functional redundancy among different Wnts. Here, we use Shh-Cre to conditionally
      delete Gpr177 (the mouse ortholog of Drosophila Wntless, Wls), a chaperon protein
      important for the sorting and secretion of Wnt proteins. Deletion of epithelial
      Gpr177 reduces Wnt signaling activity in both the epithelium and mesenchyme,
      resulting in severe hemorrhage and abnormal vasculature, accompanied by branching
      defects and abnormal epithelial differentiation. We then used multiple mouse
      models to demonstrate that Wnt/beta-catenin signaling is not only required for
      the proliferation and differentiation of mesenchyme, but also is important for
      the maintenance of smooth muscle cells through the regulation of the
      transcription factor Kruppel-like factor 2 (Klf2). Together, our studies define a
      novel mechanism by which epithelial Wnts regulate the normal development and
      maintenance of pulmonary vasculature. These findings provide insight into the
      pathobiology of congenital lung diseases, such as alveolar capillary dysplasia
      (ACD), that have abnormal alveolar development and dysmorphic pulmonary
      vasculature. 

PMID- 23884447
TI  - Correlation of breast cancer axillary lymph node metastases with stem cell
      mutations.
AB  - IMPORTANCE: Mutations in oncogenes AKT1, HRAS, and PIK3CA in breast cancers
      result in abnormal PI3K/Akt signaling and tumor proliferation. They occur in
      ductal carcinoma in situ, in breast cancers, and in breast cancer stem and
      progenitor cells (BCSCs). OBJECTIVES: To determine if variability in clinical
      presentation at diagnosis correlates with PI3K/Akt mutations in BCSCs and
      provides an early prognostic indicator of increased progression and metastatic
      potential. DESIGN, SETTING, AND PARTICIPANTS: Malignant (BCSCs) and benign stem
      cells were collected from fresh surgical specimens via cell sorting and tested
      for oncogene mutations in a university hospital surgical oncology research
      laboratory from 30 invasive ductal breast cancers (stages IA through IIIB). MAIN
      OUTCOMES AND MEASURES: Presence of AKT1, HRAS, and PIK3CA mutations in BCSCs and
      their correlation with tumor mutations, pathologic tumor stage, tumor histologic
      grade, tumor hormone receptor status, lymph node metastases, and patient age and
      condition at the last follow-up contact. RESULTS: Ten tumors had mutations in
      their BCSCs. In total, 9 tumors with BCSC mutations and 4 tumors with BCSCs
      without mutations had associated tumor present in the lymph nodes (P = .001).
      CONCLUSIONS AND RELEVANCE: Tumors in which BCSCs have defects in PI3K/Akt
      signaling are significantly more likely to manifest nodal metastases. These
      oncogenic defects may be missed by gross molecular testing of the tumor and are
      markers of more aggressive breast cancer. Molecular profiling of BCSCs may
      identify patients who would likely benefit from PI3K/Akt inhibitors, which are
      being tested in clinical trials.

PMID- 23884448
TI  - Establishing a convention for acting in healthcare simulation: merging art and
      science.
AB  - SUMMARY STATEMENT: Among the most powerful tools available to simulation
      instructors is a confederate. Although technical and logical realism is dictated
      by the simulation platform and setting, the quality of role playing by
      confederates strongly determines psychological or emotional fidelity of
      simulation. The highest level of realism, however, is achieved when the
      confederates are properly trained. Theater and acting methodology can provide
      simulation educators a framework from which to establish an acting convention
      specific to the discipline of healthcare simulation. This report attempts to
      examine simulation through the lens of theater arts and represents an opinion on
      acting in healthcare simulation for both simulation educators and confederates.
      It aims to refine the practice of simulation by embracing the lessons of the
      theater community. Although the application of these approaches in healthcare
      education has been described in the literature, a systematic way of organizing,
      publicizing, or documenting the acting within healthcare simulation has never
      been completed. Therefore, we attempt, for the first time, to take on this
      challenge and create a resource, which infuses theater arts into the practice of
      healthcare simulation.

PMID- 23884446
TI  - Notch/Rbpjkappa signaling regulates progenitor maintenance and differentiation of
      hypothalamic arcuate neurons.
AB  - The hypothalamic arcuate nucleus (Arc), containing pro-opoiomelanocortin (POMC),
      neuropeptide Y (NPY) and growth hormone releasing hormone (GHRH) neurons,
      regulates feeding, energy balance and body size. Dysregulation of this
      homeostatic mediator underlies diseases ranging from growth failure to obesity.
      Despite considerable investigation regarding the function of Arc neurons,
      mechanisms governing their development remain unclear. Notch signaling factors
      such as Hes1 and Mash1 are present in hypothalamic progenitors that give rise to
      Arc neurons. However, how Notch signaling controls these progenitor populations
      is unknown. To elucidate the role of Notch signaling in Arc development, we
      analyzed conditional loss-of-function mice lacking a necessary Notch co-factor,
      Rbpjkappa, in Nkx2.1-cre-expressing cells (Rbpjkappa cKO), as well as mice with
      expression of the constitutively active Notch1 intracellular domain (NICD) in
      Nkx2.1-cre-expressing cells (NICD Tg). We found that loss of Rbpjkappa results in
      absence of Hes1 but not of Hes5 within the primordial Arc at E13.5. Additionally,
      Mash1 expression is increased, coincident with increased proliferation and
      accumulation of Arc neurons at E13.5. At E18.5, Rbpjkappa cKO mice have few
      progenitors and show increased numbers of differentiated Pomc, NPY and Ghrh
      neurons. By contrast, NICD Tg mice have increased hypothalamic progenitors, show
      an absence of differentiated Arc neurons and aberrant glial differentiation at
      E18.5. Subsequently, both Rbpjkappa cKO and NICD Tg mice have changes in growth
      and body size during postnatal development. Taken together, our results
      demonstrate that Notch/Rbpjkappa signaling regulates the generation and
      differentiation of Arc neurons, which contribute to homeostatic regulation of
      body size. 

PMID- 23884449
TI  - Fe-promoted cross coupling of homobenzylic methyl ethers with Grignard reagents
      via sp3 C-O bond cleavage.
AB  - The first iron-catalyzed formal cross coupling of homobenzylic methyl ethers with
      alkyl Grignard reagents is realized. The reaction is proposed to proceed through
      a sequence of dehydroalkoxylation to form the vinyl-intermediate, followed by Fe
      catalyzed selective carbometalation to form a benzylic Grignard reagent. 

PMID- 23884450
TI  - Copper-catalyzed nucleophilic trifluoromethylation of propargylic halides.
AB  - Reactions of propargylic halides with trifluoromethyltrimethylsilane in the
      presence of a catalytic amount of copper(I) thiophene-2-carboxylate (CuTC) have
      been found to give the corresponding trifluoromethylated products in good to high
      yields with a high selectivity.

PMID- 23884451
TI  - Synthesis of human growth hormone-releasing hormone via three-fragment
      serine/threonine ligation (STL).
AB  - The synthesis of human growth hormone-releasing hormone (hGH-RH), by the
      chemoselective serine/threonine ligations (STLs) of three unprotected peptide
      fragments, is reported. To allow for the multiple-fragment ligation, we chose the
      Msz (p-(methylsulfinyl)benzyloxycarbonyl) group, which is compatible with the
      preparation of peptide salicylaldehyde esters via Fmoc-SPPS and readily removed
      by reductive acidolysis, to protect the serine and threonine residue at the N
      terminus. 

PMID- 23884452
TI  - The MDM2 285G-309G haplotype is associated with an earlier age of tumour onset in
      patients with Li-Fraumeni syndrome.
AB  - In the Li-Fraumeni syndrome (LFS) resulting from germline TP53 mutations, the
      MDM2 SNP309G allele has been shown to be associated with an earlier age of tumour
      onset, however the significance of this association is controversial. The 285C
      variation, also located in the MDM2 promoter, has been shown to reduce the
      strength of Sp1 binding to MDM2 promoter, antagonizing the effect of the 309G
      variation. In this study, we investigated the interaction of the MDM2 SNP285 and
      309 in a large series of 195 LFS patients. Although we observed a lower mean age
      of tumour onset in patients with MDM2 SNP309 T/G or G/G genotype (23.1 years)
      than in patients with T/T genotype (27.3 years), the difference was not
      statistically significant. In contrast, patients with the 285-309 G-G haplotype
      develop tumours 5 years earlier than patients harbouring other haplotypes (p =
      0.044). This result shows that the MDM2 285-309 G-G is a higher risk haplotype in
      patients with germline TP53 mutations. This study confirms that the MDM2 309G
      variation is deleterious when its effect is not neutralized by the 285C variation
      and illustrates the interfering effects of SNPs located within a gene acting as
      modifier factor in a Mendelian disease.

PMID- 23884453
TI  - Tension-induced neurite growth in microfluidic channels.
AB  - The generation of an effective method for stimulating neuronal growth in specific
      directions, along well-defined geometries, and in numerous cells could impact
      areas ranging from fundamental studies of neuronal evolution and morphogenesis,
      to applications in biomedical diagnostics and nerve regeneration. Applied
      mechanical stress can regulate neurite growth. Indeed, previous studies have
      shown that neuronal cells can develop and extend neurites with rapid growth rates
      under applied "towing" tensions imparted by micropipettes. Yet, such methods are
      complex and exhibit low throughputs, as the tension is applied serially to
      individual cells. Here we present a novel approach to inducing neurite growth in
      multiple cells in parallel, by using a miniaturized platform with numerous
      microchannels. Upon connection of a vacuum to these microchannels, tension can be
      applied on multiple cells simultaneously to induce the growth of neurites. A
      theoretical model was also developed to understand the effect of tension on the
      dynamics of neurite development. 

PMID- 23884454
TI  - Extreme temperatures and emergency department admissions for childhood asthma in
      Brisbane, Australia.
AB  - OBJECTIVES: To examine the effect of extreme temperatures on emergency department
      admissions (EDAs) for childhood asthma. METHODS: An ecological design was used in
      this study. A Poisson linear regression model combined with a distributed lag non
      linear model was used to quantify the effect of temperature on EDAs for asthma
      among children aged 0-14 years in Brisbane, Australia, during January 2003
      December 2009, while controlling for air pollution, relative humidity, day of the
      week, season and long-term trends. The model residuals were checked to identify
      whether there was an added effect due to heat waves or cold spells. RESULTS:
      There were 13 324 EDAs for childhood asthma during the study period. Both hot and
      cold temperatures were associated with increases in EDAs for childhood asthma,
      and their effects both appeared to be acute. An added effect of heat waves on
      EDAs for childhood asthma was observed, but no added effect of cold spells was
      found. Male children and children aged 0-4 years were most vulnerable to heat
      effects, while children aged 10-14 years were most vulnerable to cold effects.
      CONCLUSIONS: Both hot and cold temperatures seemed to affect EDAs for childhood
      asthma. As climate change continues, children aged 0-4 years are at particular
      risk for asthma.

PMID- 23884455
TI  - Pitfalls in the assessment, analysis, and interpretation of routine outcome
      monitoring (ROM) Data: results from an outpatient clinic for integrative mental
      health.
AB  - There is considerable debate about routine outcome monitoring (ROM) for
      scientific or benchmarking purposes. We discuss pitfalls associated with the
      assessment, analysis, and interpretation of ROM data, using data of 376 patients.
      206 patients (55 %) completed one or more follow-up measurements. Mixed-model
      analysis showed significant improvement in symptomatology, quality of life, and
      autonomy, and differential improvement for different subgroups. Effect sizes were
      small to large, depending on the outcome measure and subgroup. Subtle variations
      in analytic strategies influenced effect sizes substantially. We illustrate how
      problems inherent to design and analysis of ROM data prevent drawing conclusions
      about (comparative) treatment effectiveness. 

PMID- 23884457
TI  - Activating HRAS mutation in agminated Spitz nevi arising in a nevus spilus.
AB  - IMPORTANCE: Spitz nevi are benign melanocytic proliferations that can sometimes
      be clinically and histopathologically difficult to distinguish from melanoma.
      Agminated Spitz nevi have been reported to arise spontaneously, in association
      with an underlying nevus spilus, or after radiation or chemotherapy. However, to
      our knowledge, the genetic mechanism for this eruption has not been described.
      OBSERVATIONS: We report a case of agminated Spitz nevi arising in a nevus spilus
      and use exome sequencing to identify a clonal activating point mutation in HRAS
      (GenBank 3265) (c.37G->C) in the Spitz nevi and underlying nevus spilus. We also
      identify a secondary copy number increase involving HRAS on chromosome 11p, which
      occurs during the development of the Spitz nevi. CONCLUSIONS AND RELEVANCE: Our
      results reveal an activating HRAS mutation in a nevus spilus that predisposes to
      the formation of Spitz nevi. In addition, we demonstrate a copy number increase
      in HRAS as a "second hit" during the formation of agminated Spitz nevi, which
      suggests that both multiple Spitz nevi and solitary Spitz nevi may arise through
      similar molecular pathways. In addition, we describe a unique investigative
      approach for the discovery of genetic alterations in Spitz nevi.

PMID- 23884458
TI  - Metal(II) complexes based on 1,4-bis(3-pyridylaminomethyl)benzene: structures,
      photoluminescence and photocatalytic properties.
AB  - Using a novel ditopic N-donor ligand, 1,4-bis(3-pyridylaminomethyl)benzene (L),
      four metal(II)-complexes formulated as CdL(SO4)(H2O)2 (1), CdL(1,3-bdc) (1,3
      H2bdc = 1,3-benzene dicarboxylic acid) (2), PbL(1,3-bdc) (3) and ZnL(1/2)(2,5
      tdc) (2,5-H2tdc = 2,5-thiophene dicarboxylic acid) (4) have been hydrothermally
      synthesized and structurally characterized by single-crystal X-ray diffraction.
      Complexes 1 and 3 feature uninodal 4-connected non-interpenetrated sql/Shubnikov
      tetragonal plane nets with {4(4).6(2)} topology. Complex 2 exhibits a 2-nodal
      (3,4)-connected 2D V2O5-type net with (4(2).6(3).8) (4(2).6) topology. Complex 4
      exhibits a uninodal 6-connected hxl/Shubnikov plane net (3,6) with
      {3(6).4(6).5(3)} topology. The hemi-rigid L ligand possesses similar conformation
      in complexes 1, 3 and 4: the two pyridine rings of L are parallel, and the phenyl
      moiety is almost perpendicular to the two terminal pyridine rings. Complexes 1-4
      show different thermal stabilities, UV-vis absorption, emission spectra,
      photoluminescence lifetimes and they are photocatalytically active for the
      decomposition of methyl orange under UV light irradiation.

PMID- 23884459
TI  - Mitochondrial DNA ligase is dispensable for the viability of cultured cells but
      essential for mtDNA maintenance.
AB  - Multiple lines of evidence support the notion that DNA ligase III (LIG3), the
      only DNA ligase found in mitochondria, is essential for viability in both whole
      organisms and in cultured cells. Previous attempts to generate cells devoid of
      mitochondrial DNA ligase failed. Here, we report, for the first time, the
      derivation of viable LIG3-deficient mouse embryonic fibroblasts. These cells lack
      mtDNA and are auxotrophic for uridine and pyruvate, which may explain the
      apparent lethality of the Lig3 knock-out observed in cultured cells in previous
      studies. Cells with severely reduced expression of LIG3 maintain normal mtDNA
      copy number and respiration but show reduced viability in the face of alkylating
      and oxidative damage, increased mtDNA degradation in response to oxidative
      damage, and slow recovery from mtDNA depletion. Our findings clarify the cellular
      role of LIG3 and establish that the loss of viability in LIG3-deficient cells is
      conditional and secondary to the rho(0) phenotype. 

PMID- 23884460
TI  - Stress-induced condensation of bacterial genomes results in re-pairing of sister
      chromosomes: implications for double strand DNA break repair.
AB  - Genome condensation is increasingly recognized as a generic stress response in
      bacteria. To better understand the physiological implications of this response,
      we used fluorescent markers to locate specific sites on Escherichia coli
      chromosomes following exposure to cytotoxic stress. We find that stress-induced
      condensation proceeds through a nonrandom, zipper-like convergence of sister
      chromosomes, which is proposed to rely on the recently demonstrated intrinsic
      ability of identical double-stranded DNA molecules to specifically identify each
      other. We further show that this convergence culminates in spatial proximity of
      homologous sites throughout chromosome arms. We suggest that the resulting
      apposition of homologous sites can explain how repair of double strand DNA breaks
      might occur in a mechanism that is independent of the widely accepted yet
      physiologically improbable genome-wide search for homologous templates. We claim
      that by inducing genome condensation and orderly convergence of sister
      chromosomes, diverse stress conditions prime bacteria to effectively cope with
      severe DNA lesions such as double strand DNA breaks. 

PMID- 23884461
TI  - Population size dependence of fitness effect distribution and substitution rate
      probed by biophysical model of protein thermostability.
AB  - The predicted effect of effective population size on the distribution of fitness
      effects and substitution rate is critically dependent on the relationship between
      sequence and fitness. This highlights the importance of using models that are
      informed by the molecular biology, biochemistry, and biophysics of the evolving
      systems. We describe a computational model based on fundamental aspects of
      biophysics, the requirement for (most) proteins to be thermodynamically stable.
      Using this model, we find that differences in population size have minimal impact
      on the distribution of population-scaled fitness effects, as well as on the rate
      of molecular evolution. This is because larger populations result in selection
      for more stable proteins that are less affected by mutations. This reduction in
      the magnitude of the fitness effects almost exactly cancels the greater selective
      pressure resulting from the larger population size. Conversely, changes in the
      population size in either direction cause transient increases in the substitution
      rate. As differences in population size often correspond to changes in population
      size, this makes comparisons of substitution rates in different lineages
      difficult to interpret. 

PMID- 23884462
TI  - Arthroscopic treatment of iliopsoas impingement (IPI) after total hip
      replacement.
AB  - PURPOSE: The purpose of the study was to present our arthroscopic surgical
      technique and the results in patient with an iliopsoas impingement (IPI) syndrome
      after a hip replacement. MATERIALS AND METHODS: Between 1999 and 2011, 35
      patients with the clinical picture of an IPI after total hip replacement were
      diagnosed and treated arthroscopically. The age was ranged from 58 to 82 years.
      All patients underwent conservative treatment for at least 6 months without
      success. The indication for the arthroscopic procedure was the failure of the
      conservative therapy as well as typical clinical signs as painful hip flexion, a
      positive local anesthesia test and radiological evidence of the presence of a
      prominent anterior acetabular component. The arthroscopic treatment was performed
      in all patients with anterior capsulotomy and partial capsulectomy of the hip
      joint. After identification of the pathology an arthroscopic release of the
      iliopsoas tendon in the region of the proved lesion was performed. The average
      follow-up period was 3.6 years (6 months to 12 years). RESULTS: In all patients
      osseous integrated acetabular components were found. In six cases there was a
      surface replacement, in three cases it was a cementless screw-in cup and in the
      other three cases it was a cementless modular press-fit cup. 8 out of 12 patients
      suffered from a hip dysplasia with a secondary osteoarthritis. After establishing
      an anterior capsular window arthroscopically, the iliopsoas tendon could be
      visualized in all cases. In addition to multiple local tendinitis all patients
      already showed mechanical limitation with partial rupture of variable extent in
      the iliopsoas tendon. During the arthroscopy the lesion was detected at the level
      of the anterior prominent acetabular component as well as distal to it. 10 out of
      12 patients reported immediately after postoperative mobilization that the
      typical preoperative complaints have disappeared. Two patients still had residual
      pain. In one of those patients this was relieved by the time of the follow-up
      examination. Clinically a temporary weakness of hip flexion in the first days of
      the postoperative period was detected. In the first follow-up 6 weeks later there
      was no evidence of weakness in any of the patients. CONCLUSION AND CLINICAL
      RELEVANCE: An arthroscopic release of the iliopsoas tendon with evidence of
      iliopsoas impingement after total hip replacement gives predictably good results.
      A clinically relevant weakness of hip flexion is not expected after the
      procedure.

PMID- 23884463
TI  - Proximal radioulnar translocation associated with elbow dislocation and radial
      neck fracture in child: a case report and review of literature.
AB  - Proximal radioulnar translocation with radial neck fracture and elbow dislocation
      is extremely rare. We report a case of a 5-year-old boy who was presented with
      elbow dislocation, and proximal radioulnar translocation was diagnosed a day
      after the injury. Mini-open technique was used to reduce the translocation and
      radial neck fracture. The patient finally regained full range of elbow motion and
      forearm rotation. This case had clinical importance in that the reverse
      instability of the elbow was observed compared with the previous reports. 

PMID- 23884464
TI  - When killers become helpers.
AB  - Interplay between a natural killer (NK)-cell receptor, NKp30, and other cells in
      the salivary glands profoundly affects pathogenesis of the autoimmune disease
      Sjogren's syndrome (Rusakiewicz et al., this issue). 

PMID- 23884465
TI  - Preventing newborn infection with maternal immunization.
AB  - Group B streptococcal disease is a common cause of bacterial sepsis in newborns
      and is often fatal. To protect these babies, a vaccination program must target
      pregnant women for immunization so that the resulting antibodies can be passively
      delivered from the mother to the fetus. Scientists met in Siena, Italy, to
      discuss potential approaches to maternal immunization for the prevention of
      perinatal group B streptococcal disease. 

PMID- 23884466
TI  - TGFbeta receptor mutations impose a strong predisposition for human allergic
      disease.
AB  - Transforming growth factor-beta (TGFbeta) is a multifunctional cytokine that
      plays diverse roles in physiologic processes as well as human disease, including
      cancer, heart disease, and fibrotic disorders. In the immune system, TGFbeta
      regulates regulatory T cell (Treg) maturation and immune homeostasis. Although
      genetic manipulation of the TGFbeta pathway modulates immune tolerance in mouse
      models, the contribution of this pathway to human allergic phenotypes is not well
      understood. We demonstrate that patients with Loeys-Dietz syndrome (LDS), an
      autosomal dominant disorder caused by mutations in the genes encoding receptor
      subunits for TGFbeta, TGFBR1 and TGFBR2, are strongly predisposed to develop
      allergic disease, including asthma, food allergy, eczema, allergic rhinitis, and
      eosinophilic gastrointestinal disease. LDS patients exhibited elevated
      immunoglobulin E levels, eosinophil counts, and T helper 2 (TH2) cytokines in
      their plasma. They had an increased frequency of CD4(+) T cells that expressed
      both Foxp3 and interleukin-13, but retained the ability to suppress effector T
      cell proliferation. TH2 cytokine-producing cells accumulated in cultures of naive
      CD4(+) T cells from LDS subjects, but not controls, after stimulation with
      TGFbeta, suggesting that LDS mutations support TH2 skewing in naive lymphocytes
      in a cell-autonomous manner. The monogenic nature of LDS demonstrates that
      altered TGFbeta signaling can predispose to allergic phenotypes in humans and
      underscores a prominent role for TGFbeta in directing immune responses to
      antigens present in the environment and foods. This paradigm may be relevant to
      nonsyndromic presentations of allergic disease and highlights the potential
      therapeutic benefit of strategies that inhibit TGFbeta signaling. 

PMID- 23884467
TI  - An integrated clinico-metabolomic model improves prediction of death in sepsis.
AB  - Sepsis is a common cause of death, but outcomes in individual patients are
      difficult to predict. Elucidating the molecular processes that differ between
      sepsis patients who survive and those who die may permit more appropriate
      treatments to be deployed. We examined the clinical features and the plasma
      metabolome and proteome of patients with and without community-acquired sepsis,
      upon their arrival at hospital emergency departments and 24 hours later. The
      metabolomes and proteomes of patients at hospital admittance who would ultimately
      die differed markedly from those of patients who would survive. The different
      profiles of proteins and metabolites clustered into the following groups: fatty
      acid transport and beta-oxidation, gluconeogenesis, and the citric acid cycle.
      They differed consistently among several sets of patients, and diverged more as
      death approached. In contrast, the metabolomes and proteomes of surviving
      patients with mild sepsis did not differ from survivors with severe sepsis or
      septic shock. An algorithm derived from clinical features together with
      measurements of five metabolites predicted patient survival. This algorithm may
      help to guide the treatment of individual patients with sepsis. 

PMID- 23884468
TI  - NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease characterized by
      a lymphocytic exocrinopathy. However, patients often have evidence of systemic
      autoimmunity, and they are at markedly increased risk for the development of non-
      Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon
      (IFN) signature is present among subsets of pSS patients, although the precise
      etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific
      activating receptor regulating the cross talk between NK and dendritic cells and
      type II IFN secretion. We performed a case-control study of genetic polymorphisms
      of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter
      was associated with reduced gene transcription and function as well as protection
      to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were
      significantly increased among pSS patients compared with controls and correlated
      with higher NCR3/NKp30 but not CD16-dependent IFN-gamma secretion by NK cells.
      Excess accumulation of NK cells in minor salivary glands correlated with the
      severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by
      salivary epithelial cells. These findings suggest that NK cells may promote an
      NKp30-dependent inflammatory state in salivary glands and that blockade of the
      B7H6/NKp30 axis could be clinically relevant in pSS. 

PMID- 23884470
TI  - The proximal origins of the flexor-pronator muscles and their role in the dynamic
      stabilization of the elbow joint: an anatomical study.
AB  - PURPOSE: The purpose of this study was to anatomically investigate the proximal
      origin of flexor-pronator muscles (FPMs) and clarify their contribution to
      dynamic stabilization of the elbow joint during valgus stress. METHODS: 52 elbows
      from 26 donated formalin-fixed cadavers were examined. The pronator teres muscle
      (PT), flexor carpi radialis muscle (FCR), palmaris longus muscle (PL), flexor
      digitorum superficialis muscle (FDS), and flexor carpi ulnaris muscle (FCU) were
      identified, and their proximal origin and relationship to the anterior bundle of
      the medial ulna collateral ligament (AOL) were macroscopically and histologically
      investigated. RESULTS: The PT, FCR, PL, and FDS converged and formed a common
      tendon at their proximal origin (the anterior common tendon: ACT). The ACT was
      attached to the medial epicondyle and the joint capsule, just anterior and
      parallel to the AOL. The histological morphology of the ACT was quite similar to
      that of the AOL. The ulnar head of the PT was observed in 48 of 52 elbows (92.3
      %), just behind the humeral head of PT. It mainly originated from the anterior
      edge of the sublime tubercle, while the upper part of ulnar head transitioned
      directly into the thickened joint capsule just anterior to the AOL. CONCLUSION:
      The proximal attachment of the FPMs had a characteristic morphology. According to
      our results, the ACT and PT might assist the AOL by sharing static and dynamic
      traction forces applied to the medial elbow joint.

PMID- 23884471
TI  - The evolution of dietary therapy for neurologic disorders.

PMID- 23884469
TI  - CaMKII is essential for the proasthmatic effects of oxidation.
AB  - Increased reactive oxygen species (ROS) contribute to asthma, but little is known
      about the molecular mechanisms connecting increased ROS with characteristic
      features of asthma. We show that enhanced oxidative activation of the
      Ca(2+)/calmodulin-dependent protein kinase (ox-CaMKII) in bronchial epithelium
      positively correlates with asthma severity and that epithelial ox-CaMKII
      increases in response to inhaled allergens in patients. We used mouse models of
      allergic airway disease induced by ovalbumin (OVA) or Aspergillus fumigatus (Asp)
      and found that bronchial epithelial ox-CaMKII was required to increase a ROS- and
      picrotoxin-sensitive Cl(-) current (ICl) and MUC5AC expression, upstream events
      in asthma progression. Allergen challenge increased epithelial ROS by activating
      NADPH oxidases. Mice lacking functional NADPH oxidases due to knockout of p47 and
      mice with epithelial-targeted transgenic expression of a CaMKII inhibitory
      peptide or wild-type mice treated with inhaled KN-93, an experimental small
      molecule CaMKII antagonist, were protected against increases in ICl, MUC5AC
      expression, and airway hyperreactivity to inhaled methacholine. Our findings
      support the view that CaMKII is a ROS-responsive, pluripotent proasthmatic signal
      and provide proof-of-concept evidence that CaMKII is a therapeutic target in
      asthma. 

PMID- 23884473
TI  - Natural history of skeletal-related events in patients with breast, lung, or
      prostate cancer and metastases to bone: a 15-year study in two large US health
      systems.
AB  - PURPOSE: To document the risk of skeletal complications in patients with bone
      metastases from breast cancer (BC), lung cancer (LC), or prostate cancer (PC) in
      routine clinical practice. METHODS: We used data from two large US health systems
      to identify patients aged >=18 years with primary BC, LC, or PC and newly
      diagnosed bone metastases between January 1, 1995 and December 31, 2009.
      Beginning with the date of diagnosis of bone metastasis, we estimated the
      cumulative incidence of skeletal-related events (SREs) (spinal cord compression,
      pathologic fracture, radiation to bone, bone surgery), based on review of medical
      records, accounting for death as a competing risk. RESULTS: We identified a total
      of 621 BC, 477 LC, and 721 PC patients with newly diagnosed bone metastases. SREs
      were present at diagnosis of bone metastasis in 22.4, 22.4, and 10.0 % of BC, LC,
      and PC patients, respectively. Relatively few LC or PC patients received
      intravenous bisphosphonates (14.8 and 20.2 %, respectively); use was higher in
      patients with BC, however (55.8 %). In BC, cumulative incidence of SREs during
      follow-up was 38.7 % at 6 months, 45.4 % at 12 months, and 54.2 % at 24 months;
      in LC, it was 41.0, 45.4, and 47.7 %; and in PC, it was 21.5, 30.4, and 41.9 %.
      More than one half of patients with bone metastases had evidence of SREs (BC:
      62.6 %; LC: 58.7 %; PC: 51.7 %), either at diagnosis of bone metastases or
      subsequently. CONCLUSIONS: SREs are a frequent complication in patients with
      solid tumors and bone metastases, and are much more common than previously
      recognized in women with BC.

PMID- 23884474
TI  - Evaluation of interactions between metal ions and nonionic surfactants in high
      concentration HCl using low-pressure high-performance liquid chromatography with
      low-flow-resistance polystyrene-based monolithic column.
AB  - A method for evaluating the interactions between metal ions and nonionic
      surfactants in aqueous solutions containing high-concentration HCl, using gas
      pressure-driven low-pressure high-performance liquid chromatography (LP-HPLC) as
      a highly acid-resistant HPLC system, was developed. To construct the LP-HPLC for
      this purpose, poly(styrene-co-divinylbenzene)-based low-flow-resistance
      monolithic columns tolerant to highly acidic conditions were prepared using low
      conversion thermal polymerization. Thermal polymerization at 65  degrees C for
      1.5 h (monomer conversions, 33% for styrene and 59% for divinylbenzene) allowed
      preparation of a column with both high separation efficiency (around 60,000
      plates m(-1) for alkylbenzenes) and a quite low back pressure of 0.14 MPa at a
      linear flow rate of 1 mm s(-1) (2.8 * 10(-13) m(2) in permeability). The base
      column prepared under the above conditions was coated with a nonionic surfactant,
      polyoxyethylene nonylphenyl ether (PONPE, average oxyethylene unit numbers (n) =
      3, 7.5, 15, and 20), and used for evaluation of the interactions between PONPEs
      and metal ions in 6 M HCl. The interactions between PONPEs and Au(III), Ga(III),
      Fe(III), Zn(II), and Cu(II) were successfully evaluated using both breakthrough
      and chromatographic methods. Furthermore, a study of the effect of the
      polyoxyethylene (POE) chain length revealed that the use of PONPE with the longer
      POE moiety enhanced the magnitude of the interaction together with the increase
      in the amount of oxyethylene (OE) units coated on the monolith. Moreover, the
      interactions of metal ions with a single OE unit were almost constant in the
      range of n = 7.5-20, whereas the suppression of the interaction between Au(III)
      with the shortest PONPE chain (n = 3) was also observed.

PMID- 23884475
TI  - Dress-up chiral columns for the enantioseparation of amino acids based on
      fluorous separation.
AB  - In this paper, we report a new type of chiral high-performance liquid
      chromatography (HPLC) column--a so-called dress-up chiral column--featuring a
      chiral stationary phase adsorbed reversibly in a commercial fluorous HPLC column
      through fluorous interactions. We synthesized perfluroalkylated proline
      derivatives as chiral stationary phase compounds and then adsorbed them
      reversibly in the fluorous HPLC column through the pumping of their solutions. By
      using this dress-up chiral column and fluorophobic elution of an aqueous
      copper(II) sulfate/MeOH mixture, we could enantioseparate seven racemic amino
      acids within 40 min. When we washed the dress-up chiral column with fluorophilic
      tetrahydrofuran or MeOH, the adsorbed chiral stationary phase compounds desorbed
      from the column, completely destroying its enantioseparation ability. The
      relative standard deviation of the retention times, the number of theoretical
      plates, and the resolution for each of four preparations of the dress-up columns
      were all less than or equal to 9.53% in 20-times repeated analysis, and were all
      less than or equal to 18.7% in four different preparations, respectively.

PMID- 23884476
TI  - Determination of ATP using a double-receptor sandwich method based on molecularly
      imprinted membrane and fluorescence-labeled uranyl-salophen complex.
AB  - A double-receptor sandwich method for the fluorescence determination of adenosine
      triphosphate (ATP) is proposed in this paper. The solid phase receptor on the
      surface of glass slides is a molecularly imprinted membrane (MIM) containing an
      artificial nanocavity. It is constructed by a molecular imprinting technique
      using adenosine monophosphate (AMP) as a template molecule. The labeled receptor
      is a uranyl-salophen complex containing a fluorescent group or uranyl-salophen
      fluorescein (USF). It is synthesized with salophen, 5-aminofluorescein, and
      uranyl. In a procedure of determining ATP, ATP in sample solution is first
      adsorbed on the surface of the glass slide through the combination of the AMP
      group in ATP with the nanocavity in MIM. Then, the adsorbed ATP binds USF through
      the coordination reaction of the phosphate group in ATP with uranyl in USF to
      form a sandwich-type structure of MIM-ATP-USF. The amount of ATP is detected
      through the fluorescence determination of USF bound on the slide. Under optimal
      conditions, the linear range for the determination of ATP is 0.3 to 4.8 nmol/mL
      with a detection limit of 0.041 nmol/mL. The proposed method has been
      successfully employed for the determination of ATP in real samples with the
      recoveries of 98.5 to 102.5 %. 

PMID- 23884477
TI  - Solution-based synthesis of wurtzite Cu2ZnSnS4 nanoleaves introduced by alpha
      Cu2S nanocrystals as a catalyst.
AB  - Cu2ZnSnS4 is a promising solar absorbing material in solar cells due to its high
      absorption coefficient and abundance on earth. We have demonstrated that wurtzite
      Cu2ZnSnS4 nanoleaves could be synthesized through a facile solution-based method.
      Detailed investigation of the growth process indicates that alpha-Cu2S
      nanocrystals are first formed and then serve as a catalyst to introduce the Cu,
      Zn, and Sn species into the nanoleaf growth for fast ionic conduction. The
      structure of the as-synthesized nanoleaves is characterized by powder X-ray
      diffraction, high-resolution transmission electron microscopy, fast Fourier
      transform, and energy dispersive X-ray spectroscopy mapping. Photoresponses of
      Cu2ZnSnS4 nanoleaves are evaluated by I-V curves of a Cu2ZnSnS4 nanoleaf film. It
      is believed that the enhancement of the photoresponse current of the Cu2ZnSnS4
      nanoleaf film can be attributed to fast carrier transport due to the single
      crystalline nature and enhanced light absorption resulting from larger absorption
      areas of the Cu2ZnSnS4 nanoleaves. 

PMID- 23884479
TI  - Core curriculum illustration: subperiosteal abscess in an adult.

PMID- 23884478
TI  - Solid-state high performance flexible supercapacitors based on polypyrrole-MnO2
      carbon fiber hybrid structure.
AB  - A solid-state flexible supercapacitor (SC) based on organic-inorganic composite
      structure was fabricated through an "in situ growth for conductive wrapping" and
      an electrode material of polypyrrole (PPy)-MnO2 nanoflakes-carbon fiber (CF)
      hybrid structure was obtained. The conductive organic material of PPy greatly
      improved the electrochemical performance of the device. With a high specific
      capacitance of 69.3 F cm(-3) at a discharge current density of 0.1 A cm(-3) and
      an energy density of 6.16 * 10(-3) Wh cm(-3) at a power density of 0.04 W cm(-3),
      the device can drive a commercial liquid crystal display (LCD) after being
      charged. The organic-inorganic composite active materials have enormous potential
      in energy management and the "in situ growth for conductive wrapping" method
      might be generalized to open up new strategies for designing next-generation
      energy storage devices. 

PMID- 23884480
TI  - OncodriveCLUST: exploiting the positional clustering of somatic mutations to
      identify cancer genes.
AB  - MOTIVATION: Gain-of-function mutations often cluster in specific protein regions,
      a signal that those mutations provide an adaptive advantage to cancer cells and
      consequently are positively selected during clonal evolution of tumours. We
      sought to determine the overall extent of this feature in cancer and the
      possibility to use this feature to identify drivers. RESULTS: We have developed
      OncodriveCLUST, a method to identify genes with a significant bias towards
      mutation clustering within the protein sequence. This method constructs the
      background model by assessing coding-silent mutations, which are assumed not to
      be under positive selection and thus may reflect the baseline tendency of somatic
      mutations to be clustered. OncodriveCLUST analysis of the Catalogue of Somatic
      Mutations in Cancer retrieved a list of genes enriched by the Cancer Gene Census,
      prioritizing those with dominant phenotypes but also highlighting some recessive
      cancer genes, which showed wider but still delimited mutation clusters.
      Assessment of datasets from The Cancer Genome Atlas demonstrated that
      OncodriveCLUST selected cancer genes that were nevertheless missed by methods
      based on frequency and functional impact criteria. This stressed the benefit of
      combining approaches based on complementary principles to identify driver
      mutations. We propose OncodriveCLUST as an effective tool for that purpose.
      AVAILABILITY: OncodriveCLUST has been implemented as a Python script and is
      freely available from http://bg.upf.edu/oncodriveclust CONTACT:
      nuria.lopez@upf.edu or abel.gonzalez@upf.edu SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 23884482
TI  - Announcing new changes at JDD.

PMID- 23884481
TI  - Professor Kahp-Yang Suh, 1972-2013.

PMID- 23884483
TI  - A message from JDD's new co-editor-in-chief.

PMID- 23884484
TI  - The history of aesthetic medicine and surgery.
AB  - The history of beauty is as old as mankind itself--throughout history people have
      tried to improve their attractiveness and to enhance their beauty. The technical
      basis for many of nowadays procedures like lipoplasty, breast augmentation or
      rhinoplasty was thereby initiated more than a hundred years ago and evolved to
      the modern standards of today. The aim of this article is to recall the early
      days of aesthetic medicine and show the swift progress up to the highly
      specialized medical discipline of our modern time. Combining the past, present
      and future of aesthetic medicine, allows to incorporate this perspective and
      ultimately to delivery better patient care.

PMID- 23884485
TI  - Auto-classification of acne lesions using multimodal imaging.
AB  - Differentiating inflammatory and non-inflammatory acne lesions and obtaining
      lesion counts is pivotal part of acne evaluation. Manual lesion counting has
      reliably demonstrated the clinical efficacy of anti-acne products for decades.
      However, maintaining assessment consistency within and across acne trials is an
      important consideration since lesion counting can be subjective to the individual
      evaluators, and the technique has not been rigorously standardized. VISIA-CR is a
      multi-spectral and multi-modal facial imaging system. It captures fluorescence
      images of Horn and Porphyrin, absorption images of Hemoglobin and Melanin, and
      skin texture and topography characterizing broad-spectrum polarized and non
      polarized images. These images are analyzed for auto-classification of
      inflammatory and non-inflammatory acne lesion, measurement of erythema, and post
      acne pigmentation changes. In this work the accuracy of this acne lesion auto
      classification technique is demonstrated by comparing the auto-detected lesions
      counts with those counted by expert physicians. The accuracy is further
      substantiated by comparing and confirming the facial location and type of every
      auto-identified acne lesion with those identified by the physicians. Our results
      indicate a strong correlation between manual and auto-classified lesion counts
      (correlation coefficient >0.9) for both inflammatory and non inflammatory lesions
      This technology has the potential to eliminate the tedium of manual lesion
      counting, and provide an accurate, reproducible, and clinically relevant
      evaluation of acne lesions. As an aid to physicians it will allow development of
      a standardized technique for evaluating acne in clinical research, as well as
      accurately choosing treatment options for their patients according to the
      severity of a specific lesion type in clinical practice

PMID- 23884486
TI  - Randomized, placebo-controlled, phase 3 study of itraconazole for the treatment
      of onychomycosis.
AB  - BACKGROUND: Itraconazole, approved for treatment of toenail fungal infection
      onychomycosis, provides antifungal activity at a dosage requiring once-daily (QD)
      administration of 2 100-mg capsules for 12 weeks. Utilizing the Meltrex(r)
      technology delivery system, a novel 200-mg formulation of itraconazole was
      developed delivering the same dosage as 2 capsules in a single tablet. METHODS:
      This phase 3, randomized, placebo-controlled trial investigated the
      noninferiority of 1 itraconazole 200-mg tablet to 2 itraconazole 100-mg capsules
      dosed QD for 12 weeks, with a 40-week follow-up period. Clinical Cure
      (Investigator's Global Assessment plus mycological examination) was the primary
      outcome measure and Clinical Improvement was a secondary endpoint. Safety and
      efficacy of itraconazole 200-mg tablets were also compared with placebo. RESULTS:
      Significantly more patients in the intent-to-treat per-protocol populations on
      itraconazole (200-mg tablet or 2 100-mg capsules) achieved Complete Cure and
      Clinical Improvement compared with placebo. For both endpoints, itraconazole 200
      mg tablet QD was noninferior to itraconazole 100-mg capsules and superior to
      placebo. All treatment groups demonstrated a similar safety profile with no new
      safety signals identified. LIMITATIONS: Absolute patient blinding was not
      possible; the number of tablets versus capsules differed, and the appearance of
      the active drugs could not be masked. However, efficacy was based on objective
      assessments from blinded investigators. CONCLUSIONS: Once-daily itraconazole 200
      mg was well-tolerated, and may be an effective alternative to 2 itraconazole 100
      mg capsules for the treatment of toenail onychomycosis. The convenience of a
      simpler dosing regimen may improve patient compliance

PMID- 23884487
TI  - Small gel particle hyaluronic acid injection technique for lip augmentation.
AB  - Optimizing the aesthetic outcome of lip augmentation with dermal fillers, such as
      small gel particle hyaluronic acid (SGP-HA), requires skillful application of a
      suitable injection technique. Moreover, achieving aesthetic goals with minimal
      risk for adverse events requires knowledge of lip anatomy and function, clinical
      experience in the use of various injection techniques, and an individualized
      treatment approach. Clinician-patient discussion of the initial assessment of lip
      presentation and global appearance of lip shape and proportion is important in
      setting treatment expectations and establishing a basis for follow-up assessment
      of the effectiveness of treatment. The effectiveness and safety of SGP-HA for lip
      augmentation was demonstrated in a recent randomized controlled trial. This
      review discusses factors influencing the choice of one or a combination of
      techniques for injection of SGP-HA for aesthetic lip augmentation.

PMID- 23884488
TI  - Reduction of facial redness with resveratrol added to topical product containing
      green tea polyphenols and caffeine.
AB  - BACKGROUND/OBJECTIVE: Many topical formulations include antioxidants to improve
      the antioxidant capability of the skin. This study evaluated the ability of a
      unique combination of antioxidants including resveratrol, green tea polyphenols,
      and caffeine to reduce facial redness. METHODS: Subjects (n=16) presenting with
      facial redness applied the resveratrol-enriched product twice daily to the entire
      face. Reduction in redness was evaluated by trained staff members and dermatology
      house staff officers. Evaluators compared clinical photographs and spectrally
      enhanced images taken before treatment and at 2-week intervals for up to 12
      weeks. RESULTS: 16 of 16 clinical images showed improvement and 13 of 16
      spectrally enhanced images were improved. Reduction in facial redness continued
      to evolve over the duration of the study period but was generally detectable by 6
      weeks of treatment. Adverse effects were not observed in any subject. CONCLUSION:
      The skin product combination of resveratrol, green tea polyphenols, and caffeine
      safely reduces facial redness in most patients by 6 weeks of continuous treatment
      and may provide further improvement with additional treatment.

PMID- 23884489
TI  - A review and update on melanocyte stimulating hormone therapy: afamelanotide.
AB  - Afamelanotide ([Nle4-D-Phe7]-alpha-MSH) is an analog of alpha-melanocyte
      stimulating hormone given as a subcutaneous injection. Afamelanotide is currently
      undergoing phase II and III trials in Europe and the US for skin diseases
      including vitiligo, erythropoietic protoporphyria, polymorphic light eruption and
      prevention of actinic keratoses in organ transplant recipients. Unregulated
      analogs and chemicals are being sold online ahead of formal approval. A number of
      counterfeit chemicals, 'Melanotans' are being sold for tanning purposes.
      Currently, afamelanotide is already on the market in Italy and Switzerland for
      patients with erythropoietic protoporphyria. This paper will review the current
      literature on this promising compound.

PMID- 23884490
TI  - The active natural anti-oxidant properties of chamomile, milk thistle, and
      halophilic bacterial components in human skin in vitro.
AB  - The number of skin cancers continues to rise, accounting for approximately 40% of
      all cancers reported in the United States and approximately 9,500 deaths per
      year. Studies have shown reactive oxygen species (ROS) type free radicals are
      linked to skin cancer and aging. Therefore, it is important for us to identify
      agents that have anti-oxidant properties to protect skin against free radical
      damage. The purpose of this research is to investigate the anti-oxidant
      properties of bisabolol, silymarin, and ectoin that are components from
      chamomile, milk thistle, and halophilic bacteria, respectively. We measured the
      ability of bisabolol, silymarin, and ectoin to modulate the hydrogen peroxide
      (H2O2)-induced upregulation of ROS free radicals in normal human skin fibroblasts
      in vitro. Using a flow cytometry-based assay, we demonstrated that varying
      concentrations of these natural components were able to inhibit upregulation of
      H2O2-generated free radicals in human skin fibroblasts in vitro. Our results
      indicate components of chamomile, milk thistle, and halophilic bacteria exhibit
      anti-oxidant capabilities and warrant further study in clinical trials to
      characterize their anti-cancer and anti-aging capabilities.

PMID- 23884491
TI  - Dermatologists' knowledge of and preferences regarding topical steroids.
AB  - BACKGROUND: Topical corticosteroids are the standard-of-care treatment for
      dermatitis, mild psoriasis, and other inflammatory skin diseases. Prescribing
      practices rely on knowledge of topical corticosteroid potency, as well as
      potential side effects including steroid allergies. PURPOSE: The primary aim of
      this study is to determine how dermatologists classify particular topical
      corticosteroids according to potency, and which products they prefer in cases
      when allergenicity is a concern, METHODS: The data were collected and analyzed
      from 105 US-based dermatologists surveyed at the 2011 Summer American Academy of
      Dermatology meeting. RESULTS: The majority of dermatologists were in agreement on
      the potency ranking of many commonly prescribed topical corticosteroids. Two
      thirds of the surveyed dermatologists expressed concern about allergy to topical
      corticosteroids. In cases of a suspected allergy, desoximetasone was the leading
      product dermatologists would choose to prescribe. LIMITATIONS: The survey was
      limited to attendees of an educational conference, possibly leading to an
      overestimation of dermatologist knowledge of topical steroids. CONCLUSIONS: This
      study shows that dermatologists are generally knowledgeable about group
      classifications of corticosteroids in terms of potency and that they can
      appropriately select a topical product with low potential for allergy

PMID- 23884492
TI  - The efficacy, safety, and tolerability of adapalene versus benzoyl peroxide in
      the treatment of mild acne vulgaris: a randomized trial.
AB  - Topical treatments, such as adapalene and benzoyl peroxide (BPO), are popular in
      mild-to-moderate acne vulgaris. This study aimed to compare the efficacy, safety
      and tolerability of adapalene and BPO in mild acne vulgaris. In this single
      center, randomized, double-blind, clinical trial, 60 patients with mild acne
      vulgaris received either topical adapalene 0.1% gel or topical BPO 2.5% gel on
      their face once daily for two months. The changes of acne lesion count
      (efficacy), any adverse effect (safety), and the patients' overall satisfaction
      (tolerability) were compared after 3 months of follow-up. In both groups the mean
      number of noninflammatory, inflammatory and total lesions decreased significantly
      from baseline (10.77+/-5.54, 9.73+/-5.09, and 20.50+/-7.54, respectively in
      adapalene group; 11.50+/-5.92, 8.43+/-5.45, and 19.93+/-9.01, respectively in BPO
      group) to the third month (1.70+/-1.68, 0.33+/-0.66, and 0.50+/-0.78,
      respectively in adapalene group; 4.23+/-4.14, 0.33+/-0.71, and 4.13+/-4.44,
      respectively in BPO group; P<0.001 for all), posttreatment. Although the mean
      number of inflammatory lesions was significantly lower in BPO receivers only at
      first month (P =0.001), the mean number of noninflammatory and total lesions was
      significantly lower in adapalene group at second (P = 0.04 and 0.03,
      respectively) and third (P =0.02 and <0.001, respectively) months, posttreatment.
      The adverse events were minimal and self-limited (26.7% in adapalene group, 20%
      in BPO group, p=0.54). The patients' overall satisfaction was good to excellent
      in 93.3% of adapalene receivers vs. 73.3% in BPO group (P=0.08). Both topical
      adapalene 0.1% and BPO 2.5% gels seem safe and effective in mild acne vulgaris,
      with a marginal tendency toward the former.

PMID- 23884493
TI  - Treating seborrheic dermatitis: review of mechanisms and therapeutic options.
AB  - Seborrheic dermatitis is one of those conditions that dermatologists and patients
      alike tend to find a routine for, and in many cases those routines are hard to
      break. And, unlike the new treatment paradigms for eczema, acne, and even actinic
      keratoses, combination therapies for addressing the disease process typically
      have not been a part of the approach to treating seborrheic dermatitis. However,
      with the advent of new therapies and vehicles as well as a better understanding
      of how neutrophils and free oxygen radicals impact inflammation,1 there are new
      options to maintain and control the disease process of seborrheic dermatitis to
      minimize flares. Although the needs of the scalp, face and chest are different,
      as are the variations in skin types, the fundamental mechanisms of the
      inflammatory process are often the same. If it is understood that seborrheic
      dermatitis is histologically classified as a papulosquamous disorder with
      paucineutrophilic and lymphocytic infiltrates, and if the trigger and etiologic
      agent most likely is Malassezia furfur, then the ideal mechanisms of action of
      therapies should be directed as such

PMID- 23884494
TI  - Acitretin prescribing patterns in women of childbearing potential.
AB  - BACKGROUND: Acitretin is indicated for severe psoriasis, but it is also a potent
      teratogen whose use should be avoided in women of childbearing potential. Topical
      medications, phototherapy, cyclosporine A, and new biologic agents provide safer
      alternatives for women of childbearing age with moderate to severe psoriasis.
      PURPOSE: To determine the demographics of acitretin prescribing patterns as an
      assessment of acitretin use in women of child-bearing potential. METHODS: We
      examined National Ambulatory Medical Care Survey (NAMCS) data from the years 1990
      2009 to determine demographic data on patients who were prescribed etretinate or
      acitretin. We used age under 50 as a proxy for childbearing potential. RESULTS:
      From 1996-2009, there were an estimated 29 million office visits for psoriasis.
      Females accounted for 14.3 million of these visits, and 6.5 million (45.6%) of
      them were under the age of 50. The NAMCS contained only one record of a female
      patient under the age of 50 being prescribed acitretin from 1996-2009, the years
      during which acitretin had been available in the United States. This corresponds
      to an estimated 2.3% of all psoriasis patients prescribed acitretin during this
      time (20,000 out of 890,000). LIMITATIONS: The NAMCS estimates national trends
      based on a large nationwide database. While the use of acitretin in women under
      50 is low, the precision of the estimate is limited by the small sample size
      provided by this database. CONCLUSIONS: There are now many alternative treatments
      besides acitretin for women of childbearing potential with moderate to severe
      psoriasis. Acitretin is used at most infrequently in this population. In females
      of reproductive potential, acitretin should be reserved for non-pregnant patients
      who are unresponsive to other therapies or whose clinical condition
      contraindicates the use of other treatments.

PMID- 23884495
TI  - Photopneumatic therapy for the treatment of keratosis pilaris.
AB  - BACKGROUND: Current treatment options for keratosis pilaris (KP) are limited and
      are often found to be unsatisfactory to patients. OBJECTIVE: Pilot study to
      determine if photopneumatic therapy (PPx) can improve the erythema and skin
      texture in KP. METHODS: Ten patients with KP were treated with one session of PPx
      on the upper arm and then evaluated one month later for treatment efficacy.
      RESULTS: Average investigator-assessed improvement was 27% in erythema and 56% in
      skin texture roughness. Average patient self-reported improvement was 52% in
      erythema and 53% in skin texture. The mean satisfaction score was 6.3 on a scale
      of 1 to 10 (median 7.5) and 8 out of 10 participants reported they would choose
      to receive PPx for their KP again in the future. LIMITATIONS: Small number of
      patients, short follow-up period, and lack of blinding of the examiner and the
      patients making recall bias possible. CONCLUSIONS: One treatment of PPx improved
      both the erythema and redness associated with KP over at least a one month
      period.

PMID- 23884497
TI  - Surgical corner: a prospective randomized evaluation of cyanoacrylate glue
      devices in the closure of surgical wounds.
AB  - BACKGROUND: The use of medical adhesives for topical wound closure is gaining in
      popularity over conventional wound closure materials such as sutures and staples.
      Adhesives provide advantages in both wound closure and patient management with
      good cosmetic outcome and surgeon and patient satisfaction reported. OBJECTIVE:
      To compare the use of two currently marketed medical adhesives; LiquiBand(r) Flow
      Control and High Viscosity Dermabond TM for the topical closure of surgical
      incisions. METHODS: In a prospective blinded manner, subjects were randomly
      assigned LiquiBand(r) or DermabondTM for topical closure of a surgical incision.
      Variables compared included ease of use, time taken to close wound, subject and
      surgeon satisfaction with device and wound closure, cosmetic outcome at 90 days,
      and complication rates. RESULTS: Use of both devices resulted in effective wound
      closure with similar high levels of cosmesis subject and surgeon satisfaction,
      with only minor complications reported. There was no statistically significant
      difference between the devices for all the parameters studied, with the exception
      that the Liquiband device was found to significantly reduce the amount of time
      required for closure. CONCLUSION: As the two devices appear substantially
      equivalent in terms of key surgeon and patient variables, product cost should be
      the primary determinant in selection of the tissue glue device.

PMID- 23884499
TI  - Erythema dyschromicum perstans in a Caucasian pediatric patient.
AB  - Erythema dyschromicum perstans (EDP), or ashy dermatosis, is characterized by
      oval, blue-gray macules, which are completely asymptomatic. In adults, the
      condition is primarily seen in patients of color, most commonly those of Hispanic
      descent, and typically follows a chronic course. We describe a pediatric case of
      EDP in a Caucasian patient. In the pediatric population, EDP is more commonly
      observed in Caucasian patients and often shows significant recovery or complete
      resolution in a matter of years. This case report outlines the differences in EDP
      between adult and pediatric patients.

PMID- 23884500
TI  - Resident rounds. Part III: case report: temporary traumatic discoloration from
      handling moss-covered firewood.
AB  - Pattern recognition remains a valuable tool in the accurate diagnosis of
      dermatologic disease. A comprehensive patient history and physical examination
      denote cornerstones of medical evaluation, and in our specialty, dermoscopy can
      supplement data gathering to allocate cutaneous eruptions into appropriate
      categories. We present a case of acute onset palmar discoloration occurring in an
      otherwise healthy patient. Correct diagnosis transpired in the clinical setting
      with tailored questioning based on careful examination and adjunct dermatoscopic
      evaluation.

PMID- 23884501
TI  - Myocosis fungoides--an update on a non-mycotic disease.
AB  - Mycosis fungoides was first described in 1806 by the French physician Jean Louis
      Alibert in a patient whose skin lesions developed into mushroom-like tumors.
      Though it is not an infectious disease, it was termed mycosis fungoides (MF) due
      to its fungating appearance. In 1870, Bazin further described MF, proposing the
      three classical stages of the cutaneous disease: patch, plaque, and tumor. The
      term cutaneous T-cell lymphoma (CTCL) was first utilized in 1975 by Lutzner et al
      to describe a group of malignant infiltrative disorders of the skin including MF
      and Sezary syndrome. CTCLs comprise a spectrum of extranodal non-Hodgkin's
      lymphomas that are characterized by primary cutaneous involvement of a dominant
      clonal T-cell. As molecular biology and immunohistochemistry techniques have
      become more developed, CTCL has become understood to be a heterogeneous assembly
      of disorders that vary with regards to clinical course, histopathology,
      therapeutic considerations, and prognosis. MF, a low-grade lymphoproliferative
      disorder, is the most common type of CTCL, comprising 54% of CTCLs. It is a rare,
      extranodal, non-Hodgkin's lymphoma and is an epidermotropic neoplasm composed of
      CD4+ (helper) lymphocytes Sezary syndrome is a related leukemic subtype of CTCL
      that presents with diffuse skin involvement as well as circulating tumor cells in
      the peripheral blood.

PMID- 23884503
TI  - Treatment of acne scars with hyaluronic acid: an improved approach.
AB  - BACKGROUND: Acne scarring is a prevalent and challenging cosmetic issue, which is
      often addressed by multiple modalities. A low-viscosity non-animal stabilized
      hyaluronic acid (NASHA) dermal filler, injected in microdoses into the mid-to
      superficial dermis, may provide a useful new approach to improving the appearance
      of depressed acne scars MATERIALS AND METHODS: Twelve consecutive patients with
      moderate to severe acne scarring, who had completed a series of fractional laser
      resurfacing, underwent microinjections of 20 mg/mL hyaluronic acid (HA) gel into
      discrete depressed acne scars on the face RESULTS: Immediate visual improvement
      was observed in all lesions. The procedure was well tolerated. Adverse events
      were limited to transient pinpoint bleeding at the injection site CONCLUSION:
      Microinjection of low viscosity HA offers a valuable technique for the treatment
      of discrete depressed acne scars

PMID- 23884505
TI  - Over-the-counter product role in the daily management of atopic dermatitis:
      achieving success with advanced technology.

PMID- 23884506
TI  - The integration of physiologically-targeted skin care in the management of atopic
      dermatitis: focus on the use of a cleanser and moisturizer system incorporating a
      ceramide precursor, filaggrin degradation products, and specific "skin-barrier
      friendly" excipients.
AB  - Atopic dermatitis (AD) may be considered the "poster disease" for exemplifying
      the significance of abnormalities of the epidermal barrier that occur
      predominantly within the stratum corneum (SC) and upper epidermis. Specifically,
      impairments of the SC permeability barrier, antimicrobial barrier, and
      immunologic barrier contribute markedly to the fundamental pathophysiology of AD.
      The multiple clinical sequelae associated with epidermal barrier impairments
      inherent to AD include dry skin, pruritus, increased skin sensitivity to
      irritants and allergens, eczematous skin changes, staphylococcal skin and
      anterior nares colonization, and increase in some cutaneous infections (ie,
      molluscum contagiosum). This article addresses the pathophysiology of AD with
      clinically relevant correlations, and discusses the scientific basis of a
      specially designed cleanser and moisturizer system that incorporates ceramide
      technology and filaggrin degradation products along with other "barrier-friendly"
      excipients.

PMID- 23884508
TI  - Onchomycosis: an overview.
AB  - Onychomycosis is a fungal infection of the nail unit, more common in toenails
      than in fingernails, and caused by a variety of fungi including dermatophytes,
      nondermatophyte molds, and <em>Candida.</em> There are 4 to 5 subtypes related to
      the method of fungal invasion of the nail unit, the most common being distal
      lateral subungual onychomycosis. Here the fungus enters the distal lateral part
      of the nail bed, the region of the hyponychium, often as an extension of tinea
      pedis. Hyperkeratosis occurs under the nail plate, resulting in detachment of the
      nail plate from the nail bed (onycholysis), with subungual thickening.

PMID- 23884509
TI  - Frequent debridement for healing of chronic wounds.

PMID- 23884510
TI  - Informatics for neurocritical care: challenges and opportunities.
AB  - Neurocritical care relies on the continuous, real-time measurement of numerous
      physiologic parameters. While our capability to obtain such measurements from
      patients has grown markedly with multimodal monitoring in many neurologic or
      neurosurgical intensive care units (ICUs), our ability to transform the raw data
      into actionable information is limited. One reason is that the proprietary nature
      of medical devices and software often prevents neuro-ICUs from capturing and
      centrally storing high-density data. Also, ICU alarm systems are often unreliable
      because the data that are captured are riddled with artifacts. Informatics is the
      process of acquiring, processing, and interpreting these complex arrays of data.
      The development of next-generation informatics tools allows for detection of
      complex physiologic events and brings about the possibility of decision support
      tools to improve neurocritical care. Although many different approaches to
      informatics are discussed and considered, here we focus on the Bayesian
      probabilistic paradigm. It quantifies the uncertainty inherent in neurocritical
      care instead of ignoring it, and formalizes the natural clinical thought process
      of updating prior beliefs using incoming patient data. We review this and other
      opportunities, as well as challenges, for the development and refinement of
      informatics tools in neurocritical care. 

PMID- 23884511
TI  - Early diagnosis of paroxysmal sympathetic hyperactivity in the ICU.
AB  - BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) is a complication of
      acquired brain injury manifesting with episodic tachycardia, tachypnea,
      hypertension, diaphoresis, hypertonia, and posturing. No universally accepted
      diagnostic criteria exist and diagnosis is often delayed until the rehabilitation
      phase. METHODS: Electronic records were screened to identify consecutive cases of
      PSH diagnosed in an intensive care unit (ICU) between 1/2006 and 8/2012 and
      assess the validity of early clinical diagnosis against formal diagnostic
      criteria. Data collected included patient demographics, brain injury etiology,
      symptoms noted by the clinician to support the diagnosis of PSH, PSH
      manifestations, therapeutic interventions, relevant brain imaging, and
      investigations to exclude alternative diagnoses. An operational set of diagnostic
      criteria based on previous literature was used for comparison. RESULTS: Fifty
      three consecutive patients with PSH were identified. Mean age was 33.6 +/- 14.5
      years (range 16-67). Traumatic brain injury was the most common etiology (30
      patients, 56.6 %) but causes were diverse. Mean time to diagnosis was 8.3 +/-
      11.0 days; 31 patients (59 %) were diagnosed within 7 days and 20 patients (38 %)
      within 3 days of admission. Tachycardia was almost uniformly present, and
      diaphoresis, fever, hypertension, and tachypnea were also present in most cases.
      Dystonia and posturing were present in less than half of patients. 89 % of
      clinically diagnosed cases met formal diagnostic criteria. CONCLUSIONS:
      Paroxysmal sympathetic hyperactivity can be diagnosed early in the ICU. Strict
      diagnostic criteria supported the clinician's diagnosis in the majority of cases.
      Diagnosis should not be rejected because of any particular sign's absence,
      especially dystonia and posturing.

PMID- 23884512
TI  - Is early DNR a self-fulfilling prophecy for patients with spontaneous
      intracerebral hemorrhage?
AB  - BACKGROUND: To investigate differences in outcome of patients with intracerebral
      hemorrhage (ICH) based on institution of do-not-resuscitate (DNR) order within
      first 24 h of admission. METHODS: A prospective registry of patients presenting
      with ICH from Jan 2006 to Dec 2008 was created. Patients with and without DNR
      orders instituted within 24 h of admission were classified as cases and controls
      respectively and were matched based on age and stroke severity. Demographics,
      intracerebral volume of hematoma, intraventricular extension of hemorrhage (IVH),
      invasive treatments, and outcomes at discharge were collected. All patients were
      followed up at least for 1 year, to determine mortality outcomes. RESULTS: Of a
      total of 245 subjects, 18 % had DNR order instituted within 24 h of admission.
      After matching, a total of 69 controls were available for 44 cases. There was no
      difference in demographics, IVH extension, volume of hemorrhage, and length of
      stay among cases and controls. Higher proportions of controls had surgical
      evacuation of the hematoma (p = 0.0125) and mechanical ventilation (p = 0.0001).
      There was no significant difference in functional outcome and survival rates
      among cases and controls at the end of 1 week, 1 month, and 1 year. CONCLUSIONS:
      DNR institution and restriction of resuscitation was not associated with poor
      outcome or difference in survival within 1 year after ICH. This indicates an
      early DNR probably does not lead to a self-fulfilling prophecy in this
      population, and might be explained by our practice, were DNR orders do not impact
      the level of supportive medical care we provide.

PMID- 23884515
TI  - Gallstone pancreatitis without cholecystectomy.
AB  - IMPORTANCE: Current guidelines recommend that patients with an initial episode of
      gallstone pancreatitis receive cholecystectomy. However, for various reasons,
      many patients do not. OBJECTIVE: To determine the risk of developing recurrent
      gallstone pancreatitis in patients who never receive a cholecystectomy. DESIGN:
      Retrospective cohort study using electronic medical records. SETTING: Inpatient
      and outpatient. PATIENTS: All patients in Kaiser Permanente Southern California
      with a primary diagnosis of acute gallstone pancreatitis hospitalized from
      January 1, 1995, through December 31, 2010, with no previous diagnosis of
      gallstone pancreatitis documented in the medical record. INTERVENTIONS:
      Endoscopic retrograde cholangiopancreatography (ERCP) with or without
      sphincterotomy and/or stent placement, or no intervention. MAIN OUTCOMES AND
      MEASURES: Recurrent acute pancreatitis. RESULTS: A total of 1119 patients were
      identified. The median age at diagnosis was 63 years. Among the patients, 802
      received no intervention and 317 received ERCP. After a median follow-up of 2.3
      years, the overall risk of recurrent pancreatitis was 14.6%; it was 8.2% and
      17.1% in patients who had ERCP and no intervention, respectively (P < .001). The
      median time to recurrence was 11.3 and 10.1 months in the patients who had ERCP
      and no intervention, respectively. Kaplan-Meier estimates of recurrence for 1, 2,
      and 5 years in the ERCP group were 5.2%, 7.4%, and 11.1%, compared with 11.3%,
      16.1%, and 22.7% in the no-intervention group (hazard ratio = 0.45; 95% CI, 0.30
      0.69; P < .001). Charlson Comorbidity Index and intensive care unit stay were
      independently associated with recurrence, whereas age, sex, and admission Ranson
      score were not associated. CONCLUSIONS AND RELEVANCE: In patients who did not
      undergo cholecystectomy, the risk of recurrent pancreatitis is significant.
      Endoscopic retrograde cholangiopancreatography mitigates this risk and should be
      considered during initial hospitalization if cholecystectomy is not done.

PMID- 23884514
TI  - 9-Cis retinoic acid protects against methamphetamine-induced neurotoxicity in
      nigrostriatal dopamine neurons.
AB  - Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. 9
      Cis retinoic acid (9cRA), a biologically active derivative of vitamin A, has
      protective effects against damage caused by H(2)O(2) and oxygen-glucose
      deprivation in vitro as well as infarction and terminal deoxynucleotidyl
      transferase-mediated dNTP nick-end labeling (TUNEL) labeling in ischemic brain.
      The purpose of this study was to examine if there was a protective role for 9cRA
      against MA toxicity in nigrostriatal dopaminergic neurons. Primary dopaminergic
      neurons, prepared from rat embryonic ventral mesencephalic tissue, were treated
      with MA. High doses of MA decreased tyrosine hydroxylase (TH) immunoreactivity
      while increasing TUNEL labeling. These toxicities were significantly reduced by
      9cRA. 9cRA also inhibited the export of Nur77 from nucleus to cytosol, a response
      that activates apoptosis. The interaction of 9cRA and MA in vivo was next
      examined in adult rats. 9cRA was delivered intracerebroventricularly; MA was
      given (5 mg/kg, 4*) one day later. Locomotor behavior was measured 2 days after
      surgery for a period of 48 h. High doses of MA significantly reduced locomotor
      activity and TH immunoreactivity in striatum. Administration of 9cRA antagonized
      these changes. Previous studies have shown that 9cRA can induce bone
      morphogenetic protein-7 (BMP7) expression and that administration of BMP7
      attenuates MA toxicity. We demonstrated that MA treatment significantly reduced
      BMP7 mRNA expression in nigra. Noggin (a BMP antagonist) antagonized 9cRA-induced
      behavioral recovery and 9cRA-induced normalization of striatal TH levels. Our
      data suggest that 9cRA has a protective effect against MA-mediated
      neurodegeneration in dopaminergic neurons via upregulation of BMP.

PMID- 23884516
TI  - Attentional control of the creation and retrieval of stimulus-response bindings.
AB  - Two experiments studied the degree to which the creation and retrieval of
      episodic feature bindings is modulated by attentional control. Experiment 1
      showed that the impact of bindings between stimulus and response features varies
      as a function of the current attentional set: only bindings involving stimulus
      features that match the current set affect behavior. Experiment 2 varied the time
      point at which new attentional sets were implemented-either before or after the
      processing of the to-be-integrated stimuli and responses. The time point did not
      matter, suggesting that the attentional set has no impact on feature integration
      proper but controls which features get access to and can thus trigger the
      retrieval of bindings. 

PMID- 23884517
TI  - [Care workers in times of demographic change. Problems, challenges, and
      strategies for solutions].

PMID- 23884513
TI  - Guidelines on the use of iodinated contrast media in patients with kidney disease
      2012: digest version. JSN, JRS, and JCS Joint Working Group.

PMID- 23884518
TI  - [Demographic change, people needing long-term care, and the future need for
      carers. An overview].
AB  - Both the number of people in need of long-term care and the number of carers will
      grow strongly in the future. This development is influenced by several factors.
      Firstly, demographic change will increase the number of people in need of long
      term care. This article analyzes how demographic change is shifting the balance
      of age groups that need long-term care using the"greying index" and parent
      support ratio. Secondly, changes in the health status of the elderly modify the
      need for long-term care. A decrease in morbidity could reduce the future need for
      long-term care. Thirdly, two thirds of all people in need of long-term care are
      cared for at home today, for the most part by their relatives exclusively. The
      demographic potential for family care will not increase in future. Thus, it can
      be assumed that a greater part of long-term care will be relocated to
      institutions and that this will increase the demand for professional carers. A
      synopsis of diverse projections reveals that in future, the number of carers
      required for long-term care will be much higher than that of today. 

PMID- 23884519
TI  - [Impact of demographic change on the employment for carers in central Germany. An
      analysis of Saxony, Saxony-Anhalt, and Thuringia].
AB  - This article provides a detailed analysis of the current state of the labor
      market for long-term carers in the Federal States of Saxony, Saxony-Anhalt, and
      Thuringia and uses model calculations to derive trends until the year 2025.
      Examining the current situation, we look at the ratio of unemployed persons to
      registered job vacancies, the duration of the vacancy, the short-term and long
      term employment trend, the replacement demand, and the job-specific unemployment
      rates. In addition, wages are discussed as the central clearing mechanism between
      labor demand and labor supply. Employment bottlenecks are evident for nurses and
      social workers, which will be exacerbated in the future owing to a strong
      demographic change. On the one hand, demand for long-term care will grow along
      with the increase of elderly people. On the other hand, the labor force potential
      and hence the supply of long-term carers will decrease. Model calculations show
      that in these three Federal States, between 18,100 and 31,700 long-term carers
      (in full-time employment) will additionally be needed for the elderly. Employers
      in this field will face grave challenges in meeting these needs. 

PMID- 23884520
TI  - [The Hessian care monitor. Transparency on regional labor markets].
AB  - The Hessian Care Monitor is a Web-based monitoring system of the regional care
      labor market. It contains information on the current labor market and on future
      developments. Official statistics are analyzed, primary data are collected, and
      forecasts are calculated. Since 2008, the demand for nurses in Hesse has been
      higher than the supply. In 2010, there was a lack of more than 4,400 nurses.
      Moreover, in 2025, around 5,500 additional nurses will be needed to meet the
      increasing demand arising from demographic changes. However, there are three
      different regional patterns: regions with high current shortages but little
      additional demand in the future; regions with low current shortages but large
      future needs; and regions with high current shortages and large future demand.
      Appropriate strategies for handling labor shortages have to be selected according
      to the different regional patterns. 

PMID- 23884521
TI  - [Long-term care in Europe. Challenges and strategies in nursing staff
      management].
AB  - Across Europe, long-term care (LTC) is one of the most challenging areas of
      social policy. Despite a growing awareness of the problems and improved data,
      current institutional reforms are an ineffective response to demographic change.
      This article aims to provide an overview of the challenges of future nursing and
      care staff in LTC in Europe, and to discuss the German case in a wider European
      context. We focus on the nursing workforce and on the link between current and
      prospective analyses on the demand and offer of LTC services and LTC
      professionals/nursing staff. We draw on a secondary analysis of the literature
      and public statistics, especially OECD data. The European comparison shows a high
      variation in the future demand for LTC. In Germany, a number of problematic
      trends create a negative scenario: the growing demand for LTC meets with a
      decrease in nursing staff on the supply side. We conclude by suggesting
      intervention strategies that may reduce this negative scenario. 

PMID- 23884522
TI  - [Can nursing staff from abroad meet the growing demand for care? Analysis of
      labor migration in nursing professions in 2010].
AB  - Owing to demographic changes, there will probably not be enough nursing staff
      available in the future to cover the continually increasing demand for long-term
      care. Among other things, labor migration is seen as a means to meet shortages in
      care staff. This report analyzes to what extent migrant workers meet the need for
      nursing staff today, what the structure of their qualifications is, and from
      which countries they come. The results show that migrant workers in nursing
      professions mainly come from the eastern EU countries and the former Soviet
      Union. The percentage of nursing staff with a minimum qualification of 1 year of
      long-term care training is significantly lower in the group of migrant workers
      than in the group of nonmigrant workers. Given the decline of new migrant workers
      in nursing professions in the past decade, labor migration contributes only to a
      small extent toward closing this gap in the long term. In view of the increase in
      training rates and labor participation, it is to be regarded rather as a
      temporary solution. 

PMID- 23884523
TI  - [The public reputation of nursing professions].
AB  - The following article represents the main results of studies in Germany treating
      the situation of nurses in hospitals and in long term care units focussing the
      image of nursing work--on the one hand from the public's and on the other hand
      from the nurses' perspectives. The article enters into the question what the
      general public and the nurses thinks about the nursing work, the nursing work
      conditions and trust in professional caring. As a result, it can be stated that
      the rating of nursing work and nursing work conditions in public differs. Nursing
      work is higher rated in public than the nursing work conditions and the quality
      of professional caring. In the nursing community a high identification with the
      nursing profession and nursing work can be determined. But there is lower job
      satisfaction and esteem for nursing work visible.

PMID- 23884524
TI  - [Determining the quality of long-term care. A comparative analysis of
      transparency criteria, resident-related indicators, and staff assessment].
AB  - INTRODUCTION: From 2009, the quality of care in nursing homes in Germany is
      inspected, rated, and publicized. This study investigates the association between
      staff-perceived nursing quality, clinical quality indicators, and ratings of
      health insurance medical services based on the transparency of stationary care
      agreement (PTVS). METHODS: This was a cross-sectional study merging publicly
      reported data, clinical quality indicators of a national health provider system,
      and data from staff surveys. Data from 83 nursing homes were adjusted for sample
      size, age, and care level and analyzed using Kendall's tau coefficients and
      scatter plots. RESULTS: There were pronounced differences in staff-perceived
      nursing quality and some of the clinical indicators between facilities that were
      not detected by the PTVS. There was a weak association between staff-perceived
      quality and care quality rated by external inspections. No associations were
      found between the PTVS and clinical quality indicators. CONCLUSIONS: Differences
      between nursing home providers were detected to varying degrees by the three
      approaches and were if at all weakly associated. Given the aims followed by
      public reporting initiatives of nursing home providers, the results stress the
      importance of revising the PTVS.

PMID- 23884525
TI  - [What is the impact of education and training on flexible nursing management?
      Experiences from a tertiary care hospital].
AB  - Healthcare reforms and new legislations have a significant impact on patient
      care. New and more complex treatment designs and technologies are a great
      challenge for allied healthcare professionals. There is a growing demand for
      qualified allied healthcare professionals to increase productivity and to perform
      complex therapeutic regimens. Since recruitment of specialized healthcare workers
      is difficult, the University Hospital of Cologne arranges various training
      programs for allied healthcare staff. We provide more than 500 apprenticeship
      positions, 225 for nurses. Currently, 216 nursing students have been enrolled;
      thus, we have reached a 96 % capacity and could again improve last year's
      results. Some of our graduates continue their career in an academic course of
      study at university or a university of applied science. In this way nursing
      management loses qualified and dedicated employees at the bedside. In order to
      offer attractive alternatives to an academic course, it is important to
      complement basic education with advanced training and specialization. Traditional
      in-house education, basic as well as advanced training, is still the primary
      means to recruit qualified healthcare workers. Nursing management, therefore,
      still relies on this important strategic instrument for the recruitment and
      retention of staff. 

PMID- 23884526
TI  - [Are higher fertility rates a solution to the declining long-term care
      potential?].
AB  - This article addresses demographic changes with respect to future long-term care
      in Germany. The discourse focuses on fertility issues and consequences for long
      term care: Which effects can be expected on long-term care assuming a growing
      fertility rate? Are higher fertility rates a practicable and sufficient approach
      to meet the need for increasing long-term care? The comparison of different
      population forecast variants shows that past demographic trends will have strong
      effects on the future age structure in the long run, even when taking into
      account a realistic estimate of rising fertility numbers. 

PMID- 23884527
TI  - [Geriatric nursing staff retention. Opportunities, potentials, and strategies].
AB  - Retaining geriatric nurses in their line of work could be an important strategy
      to prevent the shortage of skilled staff in the future. A prerequisite for this
      is detailed knowledge of the length and structure of professional careers. The
      IWAK ( Institut fur Wirtschaft, Arbeit und Kultur) evaluated data from the German
      Social Insurance and carried out a structural analysis of the professional
      careers of geriatric nurses. Results showed that the average duration of
      professional careers is 20 years, of which 11.7 years constitute the period of
      employment and 7.8 years account for periods of inactivity. According to these
      findings, there is a considerable potential in extending professional careers and
      reducing the periods of inactivity to make better use of the existing skilled
      staff and to reduce staff shortage in this area. Concrete measures could involve
      improvement of working conditions (with the aim of avoiding long periods of
      inactivity and illness-related premature career endings as well as of increasing
      job satisfaction), creating better conditions for a good balance between work and
      family life, as well as setting up individual strategies to expand weekly working
      hours. Key players are businesses but also local authorities and politicians. 

PMID- 23884528
TI  - [Migration. Opportunities for recruitment of skilled employees in the care
      sector].
AB  - A central objective of this study was to estimate the potential workforce for the
      elderly care sector in Germany and to compare it with the predicted demand for
      nurses in 2030. The authors describe the opportunities and obstacles in
      recruiting skilled professionals from EU member states and from countries outside
      the EU. Different scenarios of how to raise labor input are discussed so as to
      determine the domestic potential until 2030 in Germany. The results show that
      only by assuming unrealistic conditions, e. g., expectations of a high full-time
      working quota or far more working women, can the domestic potential meet the
      predicted future demands. Therefore, Germany's chances of attracting skilled
      foreign workers were assessed by analyzing wage differentials, unemployment
      probabilities, demographic developments, and professional and cultural aspects
      between the countries. A major finding study is that the German labor market
      cannot provide enough nursing care professionals for the elderly care sector by
      2030. Secondly, most of the other EU member states are facing similar challenges,
      at least in the long run. Therefore, it is recommendable to intensify
      collaboration with populous Asian countries in the future. 

PMID- 23884529
TI  - [The academization of health care. An interim report in the context of current
      developments and challenges].
AB  - In the last two decades, the educational landscape for health-care training has
      been seen in a new light as a result of complex social changes. Against this
      background, the present report offers an interim appraisal and assessment of the
      process of making health care more academic in view of current developments and
      challenges. The report begins with a short description and examination of the
      present training situation at a pre-academic level; several reform ideas are also
      presented. Following this, the report reconstructs the first phase of the
      academization of health care in the 1990s before the advent of the Bachelor's and
      Master's university degrees, which were created in the framework of the Bologna
      Reforms, and in which it first became possible to academicize to a limited extent
      certain areas of the large spectrum of health-care practices. The central part of
      the report is a discussion of the present situation and the newest developments
      in the field of academic health care within the context of the Bologna process
      and further changing conditions. In the conclusion, the report discusses the
      future prerequisites that could promote a sustainable and qualitative development
      of the academization of health care. 

PMID- 23884530
TI  - [Prospective qualification requirements in nursing care. Results and conclusions
      of the BMBF research network FreQueNz].
AB  - Demographic change, advances in medicine, and innovative health care services are
      leading to changes in the professional qualification requirements for nursing and
      care staff. Detecting future trends in relation to these requirements was the
      focus of a Delphi study developed as part of the BMBF FreQueNz initiative. After
      qualitative expert interviews, data collection was organized in three consecutive
      steps, with 243 interviews realized in the second wave. It was found that home
      care will further diversify in the fields of supporting and counseling services
      as well as in palliative care, resulting in the necessary expansion of specific
      qualifications (e.g., intensive care). Moreover, there will be an increased need
      for interprofessional, intersectoral, and intercultural coordination and
      communication skills. As a consequence of the delegation of medical tasks, new
      duties for nonmedical professions in inpatient and outpatient care will also
      arise. For instance, qualifications need to be tailored to the new demands of
      assessment, diagnostics, therapy, and patient education and they should take into
      account evidence-based knowledge as well as clinical practice guidelines.
      Consequently, the system of care professionals will further diversify through
      advanced training programs and the continued academization of nursing. 

PMID- 23884531
TI  - [Service robots in elderly care. Possible application areas and current state of
      developments].
AB  - The term "Service robotics" describes semi- or fully autonomous technical systems
      able to perform services useful to the well-being of humans. Service robots have
      the potential to support and disburden both persons in need of care as well as
      nursing care staff. In addition, they can be used in prevention and
      rehabilitation in order to reduce or avoid the need for help. Products currently
      available to support people in domestic environments are mainly cleaning or
      remote-controlled communication robots. Examples of current research activities
      are the (further) development of mobile robots as advanced communication
      assistants or the development of (semi) autonomous manipulation aids and
      multifunctional household assistants. Transport robots are commonly used in many
      hospitals. In nursing care facilities, the first evaluations have already been
      made. So-called emotional robots are now sold as products and can be used for
      therapeutic, occupational, or entertainment activities. 

PMID- 23884536
TI  - [Usutu virus].

PMID- 23884537
TI  - [Coxiella burnetii -- causative agent of Q (query) fever].

PMID- 23884538
TI  - [Format for reporting to the relevant highest authorities of the Federal Ministry
      of Healthy/Federal Environmental Agency ].

PMID- 23884539
TI  - Employing tripodal carboxylate ligand to construct Co(II) coordination networks
      modulated by N-donor ligands: syntheses, structures and magnetic properties.
AB  - Hydrothermal reaction of a tripodal bridging ligand, 5-(4
      carboxyphenoxy)isophthalic acid (H3cpia) with cobalt salts modulated by N-donor
      neutral ligands leads to the formation of six novel coordination networks
      formulated as {[Co(1.5)(cpia)(o-bix)](H2O)(1.5)}n (1), {[Co2(cpia)(MU-OH)(m
      bix)]H2O}n (2), {[Co(1.5)(cpia)(m-bix)]}n (3), {[Co(1.5)(cpia)(p
      bix)(0.5)(H2O)]H2O}n (4), {[Co(2.5)(cpia)(Hcpia)(4,4'-bpy)(2.5)](H2O)3}n (5), and
      {[Co3(cpia)2(bpp)2]H2O}n (6). Compound 1 exhibits a two-dimensional, (3,8)
      connected layered architecture composed of trinuclear cobalt clusters. Compound 2
      possesses a three-dimensional dense framework with (3,8)-connected tfz-d topology
      built from butterfly-shaped tetranuclear Co4(MU3-OH)2(6+) clusters. Similar to
      compound 1, trinuclear Co clusters act as secondary building units to construct
      the final 2D layered structure modulated by m-bix and bpp ligands in compounds 3
      and 6. In compound 4, trinuclear Co clusters connected by cpia(3-) anions give
      rise to two-dimensional layers, which are further pillared by p-bix ligands to
      the three-dimensional framework. Compound 5 features a 2D, (3,4,6)-connected
      molecular network assembled from alternate binuclear and mononuclear Co building
      blocks. The magnetic investigation indicates that strong antiferromagnetic
      interactions between cobalt ions are dominant in compounds 2 and 6.

PMID- 23884540
TI  - Pichia anomala (Candida pelliculosa) fungemia in a patient with sickle cell
      disease.
AB  - This case report discusses a patient with sickle cell disease who presented with
      fungemia from Pichia anomala (teleomorph: Candida pelliculosa). The organism was
      identified as P. anomala by MALDI-TOF VITEK mass spectrometry and VITEK 2 yeast
      identification card. Pichia anomala should be considered in sickle cell patients
      with recurrent fungemia. 

PMID- 23884541
TI  - Osteopontin and adiponectin: how far are they related in the complexity of
      psoriasis?
AB  - Increasing attention has been drawn towards the involvement of both osteopontin
      (OPN) and adiponectin in psoriasis. The relationship between them has been
      studied before in the context of essential hypertension. To our knowledge,
      whether a relation between them exists in cases of psoriasis and the metabolic
      status in such patients have not been investigated. We aimed to verify their
      possible roles and relations in psoriasis and its metabolic associations. 35
      patients with psoriasis vulgaris and 35 controls were included. Patients were
      clinically assessed by PASI and investigated for the presence of metabolic
      syndrome (MetS) and/or its components. Plasma levels of OPN and adiponectin were
      measured using ELISA. On comparing psoriatics to controls, patients showed
      significantly elevated levels of OPN (90.474 +/- 21.22 vs 34.709 +/- 13.95 ng/mL)
      and significantly depressed levels of adiponectin (4,586 +/- 1.187 vs 5,905 +/-
      1.374 ng/mL), (p < 0.001). Strong negative correlation between plasma OPN and
      adiponectin was detected in patients (r = -0.912, p < 0.001), but not in
      controls. OPN elevation was related to diabetes mellitus, insulin resistance, and
      MetS. Adiponectin depression was related to body mass index, and MetS. This study
      demonstrates for the first time a significant correlation between OPN and
      adiponectin in psoriasis, hypothesized to be mostly attributed to the
      inflammatory milieu of psoriasis and MetS as well as the enhanced renin
      angiotensin-aldosterone system previously documented in psoriasis. Adjuvant
      therapies aiming at modulating levels of OPN and adiponectin are speculated to
      add benefit in psoriasis treatment and protecting against its metabolic risks. 

PMID- 23884542
TI  - The effects of cadmium and copper on embryonic and larval development of ide
      Leuciscus idus L.
AB  - The effects of Cd and Cu on embryos and larvae of the ide Leuciscus idus were
      evaluated. The ide is an European cyprinid fish, natural populations of which
      tend to decrease. The ide is also used as a bioindicator organism to evaluate
      water quality. However, sensitivity of ide early developmental stages to heavy
      metal intoxication is not known. Fish were exposed to Cd or Cu (100 MUg/L) during
      embryonic, larval or both developmental periods. Survival of the embryos, time of
      hatching, size and quality of newly hatched larvae were evaluated at the end of
      embryonic period. Correctly developed larvae from the control and Cd or Cu
      exposed groups were transferred to clean water, Cd or Cu solutions (100 MUg/L)
      immediately after hatching. Larval development was observed, and the larvae were
      photographed. Time of yolk sac resorption, onset of active feeding and swim
      bladder inflation were evaluated, and the measurements were done on body and swim
      bladder size. The results showed that exposure of embryos to Cd and Cu
      significantly reduced embryonic survival and increased frequency of body
      malformations and death in newly hatched larvae and delayed hatching. Exposure to
      Cd and Cu during larval period reduced larval survival, growth and delayed
      development (yolk utilization, beginning of active feeding and swim bladder
      inflation). Cadmium was more toxic to the ide embryos and larvae than copper.
      Exposures to metals during embryonic period alone caused adverse impact on larval
      performance even when larval development took place in clean water. However,
      exposure of embryos to Cu reduced toxic impact of metal on larvae in continuous
      Cu exposure compared to the non-preexposed fish, but no such an effect occurred
      in case of Cd exposure. The results show that even a short-term exposure to Cd or
      Cu during early development of ide may adversely affect recruitment of this
      species. Among the measured endpoints, quality of newly hatched larvae (frequency
      of body malformations and larvae dead immediately after hatching) and swim
      bladder size were the most sensitive to intoxication with both metals. Embryos
      were more sensitive to Cu intoxication than larvae, while in case of Cd,
      sensitivity of both stages was similar.

PMID- 23884543
TI  - Ovarian contractility in reared gilthead seabream (Sparus aurata L.) in different
      phases of the reproductive cycle.
AB  - Spontaneous ovarian tunica albuginea contractility was evaluated in gilthead
      seabream (Sparus aurata L.) at different phases of the reproductive cycle.
      Fourteen adult females were sampled from February to November 2012 in a
      commercial fish farm, and ovaries were removed and processed for histological and
      contractility analyses. Fish reproductive stages were evaluated on haematoxylin
      eosin-stained ovary sections or by simple macroscopic observation of hydrated
      oocytes in spawning individuals. Tunica albuginea spontaneous contractility was
      recorded by using ovary wall strips mounted in an organ bath containing modified
      Ringer's solution. Ovary macro- and microscopic analyses allowed the
      identification of three different reproductive conditions: vitellogenesis,
      spawning and regressing. The gilthead seabream tunica albuginea was capable to
      contract spontaneously, and significant differences were found in mean
      contraction amplitude among the three reproductive states, with the highest value
      recorded in individuals in regressing condition and the lowest in individuals at
      spawning stage. No differences in mean contractility frequency among the three
      different groups were found. Possible involvement of spontaneous contractility in
      facilitating developing follicle advancement towards the ovarian lumen within the
      ovary and in supporting recovery of regressing ovaries may be hypothesized. The
      low contractility observed during the final oocyte maturation and spawning phases
      does not seem to support a role of tunica albuginea during ovulation, which could
      conversely involve theca cell contraction. Alternatively, possible single
      instantaneous contractions of tunica albuginea muscle fibres, not detected in the
      present study, could occur during ovulation in response to neuro-hormonal
      stimulations; a role of abdominal wall musculature in ovary "squeezing" and
      consequent release of ovulated eggs cannot be excluded. 

PMID- 23884544
TI  - Exposure to the saturated free fatty acid palmitate alters BV-2 microglia
      inflammatory response.
AB  - Elevated levels of free fatty acids (FFAs) in plasma and increased incidence of
      chronic systemic inflammation are associated with obesity. In the brain,
      activated microglia are believed to play different roles during inflammation that
      may either be neuroprotective or promote neurodegeneration. Here, we have
      investigated the effects of FFAs on microglial response to inflammatory stimuli.
      Our results indicate that the saturated FFA palmitate on its own induces
      alternative activation of BV-2 microglia cells. Further, pre-exposure to
      palmitate changed the response of microglia to lipopolysaccharide (LPS). We show
      that palmitate affects the mRNA levels of the pro-inflammatory cytokines
      interleukin-1beta and interleukin-6. The transcription factor CCAAT/enhancer
      binding protein delta is also affected by pre-exposure to palmitate. Furthermore,
      the phagocytic activity of microglia was investigated using fluorescent beads. By
      analyzing the bead uptake by fluorescence-activated cell sorting, we found that
      palmitate alone, as well as together with LPS, stimulated the phagocytic activity
      of microglia. Taken together, our results suggest that exposure of microglia to
      increased levels of free fatty acids may alter the consequences of classical
      inflammatory stimuli. 

PMID- 23884545
TI  - Chronic exposure to light reverses the effect of maternal separation on proteins
      in the prefrontal cortex.
AB  - Animals subjected to maternal separation display behavioural and endocrine
      disturbances, as well as structural and functional changes in the prefrontal
      cortex and limbic areas. The aim of the present study was to determine the effect
      of maternal separation and treatment with either chronic constant light exposure
      or anti-depressant (escitalopram) on proteins in the prefrontal cortex. Four
      experimental groups of male Sprague-Dawley rats were subjected to (1) normal
      rearing, (2) maternal separation (3 h per day from postnatal day 2 (P2) to P14),
      (3) maternal separation followed by chronic light exposure (P42-P63) or (4)
      maternal separation followed by treatment with the anti-depressant drug,
      escitalopram (P68-P100). Groups 1-3 were treated with saline as vehicle control
      for the escitalopram-treated group. At P101, all rats were decapitated, and the
      prefrontal cortex was collected and stored at -80  degrees C. Tissue from three
      rats per group was pooled and proteins determined by isobaric tagging for
      relative and absolute quantification using matrix-assisted laser
      desorption/ionisation tandem mass spectrometry. Maternal separation led to
      disruptions in the prefrontal cortex that included hypometabolism by decreasing
      energy-related proteins (creatine kinase B, aconitate hydratase), decreased cell
      signalling (synapsin I, calmodulin, 14-3-3 protein epsilon) and impaired
      plasticity (spectrin, microtubule-associated protein). Maternal separation also
      increased dihydropyrimidinase-related protein/collapsin response mediator protein
      (CRMP) and myelin proteolipid protein. Exposure of maternally separated animals
      to constant light during adolescence reversed the hypometabolic state by
      increasing energy-related proteins in the prefrontal cortex and increasing cell
      signalling and cytoskeletal proteins and decreasing the expression of CRMP.
      Escitalopram had similar effects to light by increasing ATP synthase in
      maternally separated rats and dissimilar effects by increasing 2',3'-cyclic
      nucleotide 3'-phosphodiesterase and myelin proteolipid protein. Constant light
      exposure during adolescence reversed a range of protein changes in the prefrontal
      cortex of rats exposed to early maternal separation. The most prominent reversal
      by light treatment of maternal separation-induced protein increases in the
      prefrontal cortex was the expression of CRMP which impairs plasticity and
      neuronal signalling. The effects of light treatment overlapped partially with the
      effects of escitalopram.

PMID- 23884546
TI  - "Walk with me..." : A journey of self-directed holistic cancer education by
      medical students.
AB  - Cancer education offers an ideal opportunity to inspire and initiate medical
      students in life-long, self-directed learning. Early and innovative out-of-the
      box learning experiences, tailored to appeal to a multi-media savvy generation of
      medical students, form the theme of these reflections. Students never fail to
      surprise teachers when the seed of an idea appeals and motivates their minds.
      'Walk with me...' is the story of a journey together of students, mentors,
      patients, and the manifold professionals who manage breast cancer. 

PMID- 23884547
TI  - Responses to a theoretically adapted clinical trial education session: faith
      based sites versus rural work site dissemination.
AB  - The process for advancing biomedical knowledge depends upon recruiting an
      adequate and representative sample of individuals to voluntarily participate in
      research studies. A consistent personal barrier to cancer clinical trial
      participation is the lack of awareness and understanding related to trial
      availability, and the prevention and treatment roles participation represents. In
      particular, comprehensive community-based approaches to recruit and educate rural
      residents are needed. Moreover, consistent under representation of priority
      populations should be addressed with innovative outreach to collaborate in
      identifying culturally meaningful approaches. A theoretically adapted version of
      a component of the National Cancer Institute's "Clinical Trial Education Series"
      was assessed via educational sessions delivered through work sites and churches.
      From eight focus groups with 90 participants, we found that church leaders,
      congregants, and community members were receptive to education on cancer
      research, increased their short-term knowledge about it, and intent to
      participate in cancer studies, decreased their current anxiety about clinical
      trials participation, and provided specific suggestions for further adapting the
      educational session to be even more culturally relevant. These outcomes provide
      evidence to support the effectiveness of future customized recruitment strategies
      embedded within a community or faith-based environment that may increase
      knowledge, decrease anxiety and intent to actual participation in cancer studies,
      as well as impact study representativeness and address causes of health
      disparities. 

PMID- 23884548
TI  - Educational needs and preferred methods of learning among Florida practitioners
      who order genetic testing for hereditary breast and ovarian cancer.
AB  - With the expansion of genetic testing options due to tremendous advances in
      sequencing technologies, testing will increasingly be offered by a variety of
      healthcare providers in diverse settings, as has been observed with BRCA1 and
      BRCA2 (BRCA) gene testing over the last decade. In an effort to assess the
      educational needs and preferences of healthcare providers primarily in a
      community-based setting, we mailed a survey to healthcare providers across
      Florida who order BRCA testing. Within the packet, a supplemental card was
      included to give participants the opportunity to request free clinical
      educational resources from the investigative team. Of 81 eligible providers who
      completed the survey, most were physicians or nurse practitioners; and over 90 %
      worked in a community or private practice setting. Respondents provided BRCA
      testing services for a median of 5 years, but the majority (56 %) reported no
      formal training in clinical cancer genetics. Most respondents (95 %) expressed
      interest in formal training opportunities, with 3-day in-person weekend training
      representing the most highly preferred format. The most widely selected
      facilitators to participation were minimal requirement to take time off work and
      continuing education credits. Overall, 64 % of respondents requested free
      clinical educational resources. Preferences for informal education included
      written materials and in-person presentations; whereas accessing a DVD or website
      were less popular. Findings from our study highlight both the need for and
      interest in ongoing educational opportunities and resources among community
      providers who order BRCA testing. These results can be used to enhance
      participation of community-based providers in educational training programs by
      targeting educational resources to the most preferred format.

PMID- 23884549
TI  - The outcome of young colorectal cancer patients is controversial.

PMID- 23884550
TI  - Disc degeneration-related clinical phenotypes.
AB  - The phenotype, or observable trait of interest, is at the core of studies
      identifying associated genetic variants and their functional pathways, as well as
      diagnostics. Yet, despite remarkable technological developments in genotyping and
      progress in genetic research, relatively little attention has been paid to the
      equally important issue of phenotype. This is especially true for disc
      degeneration-related disorders, and the concept of degenerative disc disease, in
      particular, where there is little consensus or uniformity of definition. Greater
      attention and rigour are clearly needed in the development of disc degeneration
      related clinical phenotypes if we are to see more rapid advancements in knowledge
      of this area. When selecting phenotypes, a basic decision is whether to focus
      directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal
      stenosis), which is ultimately of interest, or an intermediate phenotype (e.g.
      dural sac cross-sectional area). While both have advantages, it cannot be assumed
      that associated gene variants will be similarly relevant to both. Among other
      considerations are factors influencing phenotype identification, comorbidities
      that are often present, and measurement issues. Genodisc, the European research
      consortium project on disc-related clinical pathologies has adopted a strategy
      that will allow for the careful characterisation and examination of both the
      complex clinical phenotypes of interest and their components. 

PMID- 23884551
TI  - The two papers of Hanne Albert et al. about Modic I changes of the vertebra
      published in the European Spine Journal of April 2013. Editorial.

PMID- 23884552
TI  - PMMA embolization to the left dorsal foot artery during percutaneous
      vertebroplasty for spinal metastases.
AB  - PURPOSE: Distal arterial embolization to the foot with PMMA during vertebral
      augmentation has not been previously reported. We report a rare case of distal
      PMMA embolization to the dorsal foot artery during ipsilateral percutaneous
      lumbar vertebral augmentation in a patient with spinal osteolytic metastases.
      METHODS: A 68-year-old woman was admitted because of severe disabling low back
      pain. Plain roentgenograms, MRI and CT-scan revealed osteolysis in the L4 and L5
      vertebral bodies with prevertebral soft tissue involvement. Percutaneous
      vertebroplasty with PMMA was performed in L2 to L5 vertebrae under general
      anesthesia. Intraoperatively, leakage into the segmental vessels L3 and L5 was
      observed. RESULT: Four hours after the procedure the clinical diagnosis of acute
      ischemia and drop foot on the left was made. CT-angiography justified linear
      cement leakage in the course of the left third lumbar vein and fifth lumbar
      artery, and to the ipsilateral common iliac artery. The patient was treated with
      low molecular heparin and the ischemia resolved without further sequelae 1 week
      postoperatively. CONCLUSION: PMMA leakage is a complication associated with
      vertebroplasty and kyphoplasty. Although the outcome of the PMMA embolization to
      the vessels resolved without sequelae, in our case spine surgeons and
      interventional radiologists should be aware on this rare complication in patients
      with osteolytic vertebral metastases even when contemporary cement containment
      techniques are used.

PMID- 23884554
TI  - Stimulus-driven saccades are characterized by an invariant undershooting bias: no
      evidence for a range effect.
AB  - Saccade endpoints are most frequently characterized by an undershooting bias.
      Notably, however, some evidence suggests that saccades can be made to
      systematically under- or overshoot a target based on the magnitude of the
      eccentricities within a given block of trials (i.e., the oculomotor range effect
      hypothesis). To address that issue, participants completed stimulus-driven
      saccades in separate blocks of trials (i.e., proximal vs. distal) that entailed
      an equal number of targets but differed with respect to the magnitude of their
      eccentricities. In the proximal block, target eccentricities were 3.0 degrees ,
      5.5 degrees , 8.0 degrees , 10.5 degrees  and 13.0 degrees , whereas in the
      distal block target eccentricities were 10.5 degrees , 13.0 degrees , 15.5
      degrees , 18.0 degrees  and 20.5 degrees . If the range effect represents a
      tenable hypothesis, then the magnitude of target eccentricities within each block
      should selectively influence saccade endpoint bias. More specifically, the
      eccentricities common to the proximal and distal blocks (i.e., 10.5 degrees  and
      13.0 degrees ) should elicit a systematic under- and overshooting bias,
      respectively. Results for the proximal and distal blocks showed a reliable
      undershooting bias across target eccentricities, and a direct comparison of the
      common eccentricities indicated that the undershooting bias was not modulated
      between blocks. Moreover, our results show that the presence of online target
      vision did not influence the undershooting bias. Thus, the present findings
      provide no support for an oculomotor range effect; rather, results evince the
      mediation of saccades via a control strategy that minimizes movement time and/or
      the energy requirements of the response.

PMID- 23884555
TI  - Mesenchymal stem cells from iPS cells facilitate periodontal regeneration.
AB  - Mesenchymal stem cells (MSC) have been considered as a potential therapy for the
      treatment of periodontal defects arising from periodontitis. However, issues
      surrounding their accessibility and proliferation in culture significantly limit
      their ability to be used as a mainstream treatment approach. It is therefore
      important that alternative, easily accessible, and safe populations of stem cells
      be identified. Controlled induction of induced pluripotent stem cells (iPSC) into
      MSC-like cells is emerging as an attractive source for obtaining large
      populations of stem cells for regenerative medicine. We have successfully induced
      iPSC to differentiate into MSC-like cells. The MSC-like cells generated satisfied
      the International Society of Cellular Therapy's minimal criteria for defining
      multipotent MSC, since they had plastic adherent properties, expressed key MSC
      associated markers, and had the capacity to undergo tri-lineage differentiation.
      Importantly, the resulting iPSC-MSC-like cells also had the capacity, when
      implanted into periodontal defects, to significantly increase the amount of
      regeneration and newly formed mineralized tissue present. Our results
      demonstrate, for the first time, that MSC derived from iPSC have the capacity to
      aid periodontal regeneration and are a promising source of readily accessible
      stem cells for use in the clinical treatment of periodontitis.

PMID- 23884557
TI  - Photophobic and phototropic movement of a self-oscillating gel.
AB  - A photosensitive self-oscillating gel that incorporates the Belousov-Zhabotinsky
      reaction can undergo rhythmic mechanical oscillations. We exploit the dependence
      of the oscillation frequency on light intensity to generate both photophobic and
      phototropic movement of the gel under differential illumination. Our findings may
      be used in designing intelligent sensors that can execute biomimetic behaviours. 

PMID- 23884556
TI  - Deletion of ATG5 shows a role of autophagy in salivary homeostatic control.
AB  - Autophagy is a catabolic pathway utilized to maintain a balance among the
      synthesis, degradation, and recycling of cellular components, thereby playing a
      role in cell growth, development, and homeostasis. Previous studies revealed that
      a conditional knockout of essential member(s) of autophagy in a variety of
      tissues causes changes in structure and function of these tissues. Acinar cell
      specific expression of knocked-in Cre recombinase through control of aquaporin 5
      (Aqp5) promoter/enhancer (Aqp5-Cre) allows us to specifically inactivate Atg5, a
      protein necessary for autophagy, in salivary acinar cells of Atg5(f/f);Aqp5-Cre
      mice. There was no difference in apoptotic or proliferation levels in salivary
      glands of Atg5/Cre mice from each genotype. However, H&E staining and electron
      microscopy studies revealed modestly enlarged acinar cells and accumulated
      secretory granules in salivary glands of Atg5(f/f);Aqp5-Cre mice. Salivary flow
      rates and amylase contents of Atg5/Cre mice indicated that acinar-specific
      inactivation of ATG5 did not alter carbachol-evoked saliva and amylase secretion.
      Conversely, autophagy intersected with salivary morphological and secretory
      manifestations induced by isoproterenol administration. These results identified
      a role for autophagy as a homeostasis control in salivary glands. Collectively,
      Atg5(f/f);Aqp5-Cre mice would be a useful tool to enhance our understanding of
      autophagy in adaptive responses following targeted head and neck radiation or
      Sjogren syndrome. 

PMID- 23884558
TI  - Multidisciplinary management of rectal cancer: the OSTRICH.
AB  - BACKGROUND: Disparity exists in outcomes for rectal cancer patients in the US.
      Similar problems in several European countries have been addressed by the
      creation of national networks of rectal cancer centers of excellence (CoEs) that
      follow evidence-based care pathways and specified protocols of care and process
      and are certified by regular external validation. AIM: This paper reviews the
      current status of rectal cancer care in the U.S. and examines the evidence for
      multidisciplinary rectal cancer management. A U.S. rectal cancer CoE system based
      on the existing U.K. model is proposed. METHODS: A literature search was
      performed for publications related to US rectal cancer outcomes,
      multidisciplinary management of rectal cancer, and European rectal cancer
      programs. RESULTS: U.S. rectal cancer outcomes are highly variable. The majority
      of US rectal cancer patients are treated by generalists in low-volume hospitals.
      Current evidence supports five main principles of rectal cancer care that have
      been incorporated into European rectal cancer CoE programs. These programs have
      dramatically improved rectal cancer outcomes in Scandanavian countries and the
      U.K. CONCLUSIONS: A similar CoE program should be established in the U.S. to
      improve the outcomes of rectal cancer patients.

PMID- 23884560
TI  - Accuracy of the CoaguChek XS(r) for POC INR in warfarinised children and adults
      with ventricular assist devices.

PMID- 23884559
TI  - A phase II study of intra-arterial cisplatin with concurrent radiation and
      erlotinib for locally advanced head and neck cancer.
AB  - BACKGROUND: Based on the convenient oral dosing of erlotinib and the promising
      results of biologic therapy, we undertook a phase II study with 21 patients with
      locally advanced (T3-4) lesions combining radiation with intra-arterial (IA)
      cisplatin and oral daily erlotinib for a 7-week therapy. METHODS: Treatment for
      the primary tumor and upper neck was given to a total dose of 70 Gy. Chemotherapy
      with IA cisplatin (150 mg/m(2)) was given on days 1, 8, 15, and 22 concurrently
      with radiotherapy. During the 7-week treatment period, patients were given
      erlotinib 150 mg/day. RESULTS: Overall survival is 63 %, and the
      relapse/persistent disease rate stands at 36.8 %. A total of 15.2 % of serious
      adverse event was considered related to erlotinib. CONCLUSION: Our study and
      several others now demonstrate the feasibility of combining anti-epidermal growth
      factor receptor (EGFR) therapy with chemoradiation, hint at improved survival
      outcomes with reduced distant metastatic rates, and suggest that maintenance
      therapy with anti-EGFR agent may be beneficial.

PMID- 23884561
TI  - [ProFI reduction of pediatric pulled elbow].
AB  - BACKGROUND: Pulled elbow is a common injury in children under the age of 5 years
      which is usually treated by manual reduction. Supination of the forearm is
      recommended as opposed to pronation or other maneuvers. The author has developed
      a manipulative intervention for reduction of pulled elbow in young children on
      the basis of the pronation technique and called ProFI reduction. PATIENTS AND
      METHODS: The ProFI method was performed on 41 children and the group was analyzed
      prospectively according to effectiveness of the ProFI repositioning. RESULTS:
      Among the 41 children the initial diagnosis was incorrect in 7 cases (17%) and in
      11 children (27%) more than one doctor's visit was necessary to reposition
      successfully. Repositioning with the ProFI method was immediately successful in
      all cases. CONCLUSION: The application of the ProFI method as a modified
      pronation technique was shown to provide excellent effectiveness with respect to
      the patients treated.

PMID- 23884562
TI  - [Successful preclinical thoracotomy in a 17-year-old man].
AB  - We report the case of a 17-year-old man who sustained multiple stab wounds after
      a knife attack. After arrival of the emergency medical team the patient suffered
      a cardiac arrest caused by cardiac tamponade. After emergency thoracotomy and
      open heart massage the patient developed ROSC and could be discharged 13 days
      later without neurological deficits. Prehospital thoracotomy is rarely performed
      in Austria but is the only realistic chance for survival in cases of
      hematopericardium and tamponade. Better training of emergency physicians in
      Austria concerning surgical resuscitation could increase survival rates
      especially after penetrating thoracic trauma. 

PMID- 23884563
TI  - Gestational protein restriction induces alterations in placental morphology and
      mitochondrial function in rats during late pregnancy.
AB  - The placenta acts a regulator of nutrient composition and supply from mother to
      fetus and is the source of hormonal signals that affect maternal and fetal
      metabolism. Thus, appropriate development of the placenta is crucial for normal
      fetal development. We investigated the effect of gestational protein restriction
      (GPR) on placental morphology and mitochondrial function on day 19 of gestation.
      Pregnant dams were divided into two groups: normal (NP 17 % casein) or low
      protein diet (LP 6 % casein). The placentas were processed for biochemical,
      histomorphometric and ultrastructural analysis. The integrity of rat placental
      mitochondria (RPM) isolated by conventional differential centrifugation was
      measured by oxygen uptake (Clark-type electrode). LP animals presented an
      increase in adipose tissue and triacylglycerol and a decrease in serum insulin
      levels. No alterations were observed in body, liver, fetus, or placenta weight.
      There was also no change in serum glucose, total protein, or lipid content.
      Gestational protein restriction had tissue-specific respiratory effects, with the
      observation of a small change in liver respiration (~13 %) and considerable
      respiratory inhibition in placenta samples (~37 %). The higher oxygen uptake by
      RPM in the LP groups suggests uncoupling between respiration and oxidative
      phosphorylation. In addition, ultrastructural analysis of junctional zone giant
      cells from LP placenta showed a disorganized cytoplasm, with loss of integrity of
      most organelles and intense vacuolization. The present results led us to
      hypothesize that GPR alters placental structure and morphology, induces
      sensitivity to insulin, mitochondrial abnormalities and suggests premature aging
      of the placenta. Further studies are needed to test this hypothesis.

PMID- 23884564
TI  - Current problems and working status of female anesthesiologists in Japan.
AB  - The rapid growth of the elderly population and the progress in surgical
      techniques in Japan have led to increased numbers of patients who undergo
      surgery. Anesthetics are essential for surgery. A survey conducted by the
      Japanese Society of Anesthesiologists showed that, during the past 10 years, the
      proportion of females among all the members has increased from 27 to 35 %, and
      the proportion of female councilors has risen from 3.9 to 6.7 %. However, the
      conditions of full-time employment remain inadequate for female physicians.
      Therefore, many female physicians in their 30s or older do not work as
      anesthesiologists. To support female anesthesiologists and their vital roles in
      surgical diagnosis and treatment, return-to-work assistance programs have been
      developed. It is also necessary to improve the working conditions for female
      anesthesiologists to allow them to continue their work, and to provide education
      for young female physicians to enhance their professional pride.

PMID- 23884565
TI  - Outcomes of emergency surgery for acute abdomen in dialysis patients: experience
      of a single community hospital.
AB  - PURPOSE: Long-term dialysis often causes physiological and metabolic problems
      that may affect the outcomes of surgery. The aim of this study was to elucidate
      whether emergency surgery for acute abdomen yields similar outcomes in dialysis
      patients versus non-dialysis patients. METHODS: The subjects were 126 patients
      who underwent emergency surgery for acute abdomen between January, 2007 and
      November, 2011 in our hospital. They were divided into a dialysis group (HD
      group; n = 9) and a non-dialysis group (non-HD group; n = 117) and their
      postoperative morbidity and mortality were compared. RESULTS: Postoperative
      morbidity and mortality were significantly worse in the HD group. All 9 of these
      patients succumbed to postoperative complications versus only 5 of the 117
      patients in the non-HD group. CONCLUSION: The outcomes of emergency surgery for
      acute abdomen were significantly worse for dialysis patients than for non
      dialysis patients. Prompt diagnosis, initiation of the most suitable surgical
      procedure, and meticulous postoperative cares are imperative to improving the
      surgical outcomes of dialysis patients.

PMID- 23884566
TI  - Promoting antitumor activities of hydroxycamptothecin by encapsulation into acid
      labile nanoparticles using electrospraying.
AB  - PURPOSE: Acid-labile nanoparticles are proposed to enhance the tumor targeting
      and anti-tumor therapy of hydroxycamptothecin (HCPT) in response to the acidic
      microenvironment within cells and tumor tissues. METHODS: HCPT was entrapped into
      matrix polymers containing acid-labile segments and galactose moieties (PGBELA)
      through an electrospraying technique. The antitumor activities of HCPT-loaded
      nanoparticles were evaluated both on HepG2 cells and after intravenous injection
      into H22 tumor-bearing mice. RESULTS: The electrosprayed nanoparticles were
      obtained with enhanced loading efficiency and extended release of HCPT compared
      with other nanoparticle preparation methods. The acid-lability and targeting
      capability of PGBELA nanoparticles resulted in a 5 times higher inhibitory
      activity after incubation in pH 6.8 media compared to that of pH 7.4. Animal
      studies indicated that both the blood circulation time and tumor distribution of
      PGBELA nanoparticles were significantly increased. HCPT/PGBELA nanoparticles
      indicated a superior in vivo antitumor activity and fewer side effects than other
      treatments on the basis of tumor growth, animal survival rate, tissue necrosis
      and cell apoptosis evaluation. CONCLUSION: Biodegradable PGBELA nanoparticles are
      capable of achieving site-specific drug delivery by active targeting and
      triggered release by acidic pH both in tumor tissues and after internalization
      within tumor cells, thereby providing a novel strategy for cancer treatment.

PMID- 23884567
TI  - Modulation of polyplex release from biodegradable microparticles through
      poly(ethylenimine) modification and varying loading concentration.
AB  - PURPOSE: This work investigates the effects of hyaluronic acid (HA) conjugated
      onto branched poly(ethylenimine) (bPEI) and varying loading concentrations of
      these polymers complexed with DNA on their release from poly(DL-lactic-co
      glycolic acid) (PLGA) microparticles and the transfection of target cells.
      METHODS: To examine the effect of alteration of the gene delivery polymer on the
      system, we observed the morphology, size, loading efficiency, polymer and DNA
      release, and the transfection efficiency for the microparticles formed with three
      internal phase loading concentrations during microparticle formation. RESULTS:
      Addition of HA to this vector allowed for increased loading concentration within
      these systems and significantly altered release kinetics without changing the
      morphology of the particles. The incorporation of HA onto the bPEI backbone
      significantly increased the transfection efficiency of the complexes released
      from the corresponding microparticle formulation. CONCLUSIONS: The results show
      that the modification of bPEI with HA and the concentration of loaded polymer/DNA
      complexes can significantly alter the entrapment and release profiles from PLGA
      microparticles. This is significant in that it offers insight into the effects of
      modification of gene delivery vectors on a controlled release system designed to
      achieve a sustained therapeutic response.

PMID- 23884568
TI  - Pharmacological modulation of cytotoxicity and cellular uptake of anti-cancer
      drugs by PDE5 inhibitors in lung cancer cells.
AB  - PURPOSE: Previous research has led to the recognition of a cGMP signaling pathway
      governing drug transport. This study is to investigate whether inhibitors of
      phosphodiesterase type 5 (PDE5), which increase intracellular cGMP levels,
      modulate the cytotoxicity and uptake of anti-cancer drugs in cancer cells.
      METHODS: The experiments were conducted with and without PDE5 inhibitors:
      dipyridamole, vardenafil, and/or sildenafil. The cytotoxicity of doxorubicin,
      cisplatin and oxaliplatin was determined in multiple cancer cell lines derived
      from different tissues. The cellular uptake of structurally diverse compounds was
      further examined in lung cancer cells with and without various endocytotic
      inhibitors. The tumor accumulation and the anti-tumor effect of trastuzumab were
      examined in a lung cancer xenograft mouse model. RESULTS: Dipyridamole could
      modulate the cytotoxicity of doxorubicin, cisplatin, and oxaliplatin in cancer
      cells. Particularly, PDE5 inhibitors increased cellular uptake of structurally
      diverse compounds into lung cancer cells both in vitro and in vivo. The effect of
      vardenafil on drug uptake could be blocked by endocytotic inhibitors. The growth
      of lung cancer xenograft in nude mice was significantly suppressed by addition of
      vardenafil to trastuzumab treatment. CONCLUSION: PDE5 inhibitors may increase the
      efficacy of anti-cancer drugs by increasing endocytosis-mediated cellular drug
      uptake, and thus serve as adjuvant therapy for certain cancers such as lung
      cancer.

PMID- 23884569
TI  - Caloric restriction-mediated induction of lipid metabolism gene expression in
      liver is enhanced by Keap1-knockdown.
AB  - PURPOSE: CR increases fatty acid oxidation to decrease tissue lipid content. The
      Nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH associated Protein 1
      (Keap1) pathway is an antioxidant gene regulatory pathway that has been
      previously investigated in weight gain. However, limited interaction of
      Nrf2/Keap1 and CR exists. The purpose of this study was to determine how Keap1
      knockdown (Keap1-KD), which is known to increase Nrf2 activity, affects the CR
      response, such as weight loss, hepatic lipid decrease, and induction of fatty
      acid oxidation gene expression. METHODS: C57BL/6 and Keap1-KD mice were
      maintained on 40% CR or fed ad libitum for 6 weeks. Hepatic lipid content, lipid
      metabolic gene, and miRNA expression was quantified. RESULTS: CR lowered hepatic
      lipid content, and induced fatty acid oxidation gene expression to a greater
      degree in Keap1-KD compared to C57BL/6 mice. CR differentially altered miRNA 34a,
      370, let-7b* in livers of Keap1-KD compared to C57BL/6 mice. CONCLUSIONS: CR
      induced induction of fatty acid oxidation gene expression was augmented with
      Keap1 knockdown, which was associated with differential expression of several
      miRNAs implicated in fatty acid oxidation and lipid accumulation.

PMID- 23884572
TI  - Clinical impact of FDG PET-CT on management decisions for patients with primary
      biliary tumours.
AB  - OBJECTIVES: To assess the impact on clinical management of introducing (18)F
      fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-computed
      tomography (CT) in to the work-up of patients with primary and recurrent biliary
      malignancy. METHODS: Consecutive patients with primary biliary tumours undergoing
      FDG PET-CT at a single large tertiary referral centre between November 2007 and
      September 2010 were retrospectively analysed. Findings on FDG PET-CT compared
      with CT/magnetic resonance imaging (MRI) and impact on subsequent patient
      management were evaluated. Impact was divided into: (1) major-detection of occult
      disease or characterisation of indeterminate lesion(s) on CT/MRI; (2) minor
      confirmation of suspected metastases seen on CT/MRI; (3) no impact. RESULTS: One
      hundred and eleven patients underwent 118 FDG PET-CT scans, including 30 with
      suspected gallbladder carcinoma and 81 with cholangiocarcinoma. Eighty-nine scans
      were performed for initial staging, five for restaging following neoadjuvant
      chemotherapy and 24 for suspected disease recurrence. In 33 cases (28 %), FDG PET
      CT had a major impact on subsequent patient management (39 % gallbladder
      carcinoma, 26 % intrahepatic cholangiocarcinoma and 21 % extrahepatic
      cholangiocarcinoma). FDG PET-CT had a minor impact in 20 cases (17 %) and no
      impact in 65 cases (55 %). CONCLUSIONS: By detecting occult metastatic disease
      and characterising indeterminate lesions, FDG PET-CT can have a major influence
      on clinical decision-making in primary and recurrent biliary malignancy.

PMID- 23884570
TI  - Bilayer composition, temperature, speciation effects and the role of bilayer
      chain ordering on partitioning of dexamethasone and its 21-phosphate.
AB  - PURPOSE: Models to predict membrane-water partition coefficients (Kp) as a
      function of drug structure, membrane composition, and solution properties would
      be useful. This study explores the partitioning of dexamethasone (Dex) and its
      ionizable 21-phosphate (Dex-P) in liposomes varying in acyl chain length,
      physical state, and pH. METHODS: DMPC:mPEG DMPE, DPPC:mPEG DPPE, and DSPC:mPEG
      DSPE (95:5 mol%) liposomes were prepared by thin film hydration. Kp values for
      Dex and Dex-P were determined from pH 1.5-8 by equilibrium dialysis and
      equilibrium solubility (Dex). RESULTS: Dex Kp values at 25 degrees C were 705 +/-
      24, 106 +/- 11, and 58 +/- 9 in DMPC, DPPC, and DSPC, increasing to 478 +/- 20 in
      DPPC liposomes at 45 degrees C. Both neutral and anionic species contributed to
      the Kp of Dex-P versus solution pH (1.5-8). A linear correlation was found
      between the natural logarithm of Kp and the inverse of bilayer free surface area
      (1/afree) where afree is a parameter reflecting chain ordering that depends on
      bilayer composition and temperature. CONCLUSIONS: Models of the pH dependence of
      partitioning of ionizable compounds must include contributions of both neutral
      and ionized species. Bilayer free surface area may be an important variable to
      predict Kp of drug molecules versus lipid composition and temperature.

PMID- 23884574
TI  - The role of colour duplex sonography in preoperative perforator mapping of the
      anterolateral thigh flap.
AB  - The anterolateral thigh (ALT) flap was first described in 1984. It is now widely
      used in reconstructive surgery following extensive tumour resection in head and
      neck cancer. Routine preoperative perforator mapping is recommended due to
      variability of the vascular anatomy of the flap. A wide array of diagnostic tools
      is available for this purpose, including colour duplex sonography (CDS). In this
      study, we report our experience with CDS. The number, location, and course
      (myocutaneous or septocutaneous) of ALT perforators were assessed by CDS prior to
      reconstructive surgery in 22 patients with head and neck cancer. These data were
      compared with the intraoperative anatomical findings to assess agreement and
      reliability. The positive predictive value and sensitivity of CDS in detecting
      perforator location was 89.4 and 94.4%, respectively, when compared to the
      surgical report. CDS also identified the perforator course with 100% accuracy.
      Colour duplex sonography is an effective, non-invasive, and relatively
      inexpensive technique for assessing the location of skin perforators.

PMID- 23884575
TI  - Quinuclidine compounds differently act as agonists of Kenyon cell nicotinic
      acetylcholine receptors and induced distinct effect on insect ganglionic
      depolarizations.
AB  - We have recently demonstrated that a new quinuclidine benzamide compound named
      LMA10203 acted as an agonist of insect nicotinic acetylcholine receptors. Its
      specific pharmacological profile on cockroach dorsal unpaired median neurons
      (DUM) helped to identify alpha-bungarotoxin-insensitive nAChR2 receptors. In the
      present study, we tested its effect on cockroach Kenyon cells. We found that it
      induced an inward current demonstrating that it bounds to nicotinic acetylcholine
      receptors expressed on Kenyon cells. Interestingly, LMA10203-induced currents
      were completely blocked by the nicotinic antagonist alpha-bungarotoxin. We
      suggested that LMA10203 effect occurred through the activation of alpha
      bungarotoxin-sensitive receptors and did not involve alpha-bungarotoxin
      insensitive nAChR2, previously identified in DUM neurons. In addition, we have
      synthesized two new compounds, LMA10210 and LMA10211, and compared their effects
      on Kenyon cells. These compounds were members of the 3-quinuclidinyl benzamide or
      benzoate families. Interestingly, 1 mM LMA10210 was not able to induce an inward
      current on Kenyon cells compared to LMA10211. Similarly, we did not find any
      significant effect of LMA10210 on cockroach ganglionic depolarization, whereas
      these three compounds were able to induce an effect on the central nervous system
      of the third instar M. domestica larvae. Our data suggested that these three
      compounds could bind to distinct cockroach nicotinic acetylcholine receptors. 

PMID- 23884576
TI  - Is magnetic resonance imaging assessment of the size of articular cartilage
      defects accurate?
AB  - The purpose of this study was to systematically review the literature relative to
      the following question: Is preoperative magnetic resonance imaging (MRI) an
      accurate instrument for the assessment of the size of knee articular cartilage
      defects compared with arthroscopy? A systematic search was performed in September
      2011 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from
      1985), SCOPUS (from 1996), and EMBASE (from 1974) databases. Four studies (one
      study of Level II and three studies of Level III) were identified that met the
      predetermined inclusion and exclusion criteria. The ability of MRI to
      preoperatively assess the size of cartilage lesions was highly variable. As a
      result of inconsistencies between imaging techniques, the methodological
      variability and shortcomings of the studies, and the limited amount of data
      available, a meta-analysis was not performed. There is some evidence that MRI is
      an accurate tool for preoperatively assessing the dimensions of articular
      cartilage defects. However, because of the heterogeneity of MRI sequences and the
      paucity of literature related to preoperative sizing, it is not possible to make
      definitive conclusions regarding the global clinical utility of MRI for guiding
      the selection of therapeutic strategies. 

PMID- 23884577
TI  - Phonon surface scattering controlled length dependence of thermal conductivity of
      silicon nanowires.
AB  - We present a kinetic model to investigate the anomalous thermal conductivity in
      silicon nanowires (SiNWs) by focusing on the mechanism of phonon-boundary
      scattering. Our theoretical model takes into account the anharmonic phonon-phonon
      scattering and the angle-dependent phonon scattering from the SiNWs surface. For
      SiNWs with diameter of 27.2 nm, it is found that in the case of specular
      reflection at lateral boundaries, the thermal conductivity increases as the
      length increases, even when the length is up to 10 MUm, which is considerably
      longer than the phonon mean free path (MFP). Thus the phonon-phonon scattering
      alone is not sufficient for obtaining a normal diffusion in nanowires. However,
      in the case of purely diffuse reflection at lateral boundaries, the phonons
      diffuse normally and the thermal conductivity converges to a constant when the
      length of the nanowire is greater than 100 nm. Our model demonstrates that for
      observing the length dependence of thermal conductivity experimentally, nanowires
      with smooth and non-contaminated surfaces, and measuring at low temperature, are
      preferred. 

PMID- 23884578
TI  - Genetic analysis of ADIPOQ variants and gastric cancer risk: a hospital-based
      case-control study in China.
AB  - Single-nucleotide polymorphisms (SNPs) of adiponectin (ADIPOQ), adiponectin
      receptor 1 (ADIPOR1) and ADIPOR2 genes contribute to the risk and progression of
      cancers. Here, we investigated the associations between variants of these three
      genes and the risk of gastric cancer. We genotyped six ADIPOQ SNPs, nine ADIPOR1
      SNPs and six ADIPOR2 SNPs using the Sequenom technique in a hospital-based case
      control study of patients with gastric cancer and cancer-free controls in the
      Chinese Han population. We found associations of certain variants with location
      of gastric cancer. Rs16861205 with the minor allele A in ADIPOQ, rs10773989 with
      the minor allele C and rs1044471 with the minor allele T in ADIPOR2 presented
      significant associations with a decreased risk of cardia cancer (P = 0.024, OR
      0.605, 95 % CI 0.390-0.938; P = 0.015, OR 0.699, 95 % CI 0.522-0.935; and P =
      0.022, OR = 0.703, 95 % CI 0.519-0.951, respectively). ADIPOQ rs16861205 with
      minor allele A displayed an association with an increased risk of body cancer (P
      = 0.010, OR 1.821, 95 % CI 1.148-2.890). Further stratified analysis of the
      patients indicated that there were significant correlations for rs1342387A/G (P =
      0.027) and rs16861205A/G (P = 0.000) with tumor location; rs16850799A/G (P =
      0.004) and rs2058033C/A (P = 0.003) with invasion depth; rs16850799A/G (P =
      0.019) with the tumor-node-metastasis stage; rs16850799A/G (P = 0.016),
      rs1501299A/C (P = 0.005) and rs1063538C/T (P = 0.017) with alcohol consumption;
      rs11612414A/G (P = 0.040) and rs12733285T/C (P = 0.005) with salted food;
      rs1063538C/T (P = 0.043) with family history of gastric cancer; and rs11612414A/G
      (P = 0.029) with gender. Adiponectin expression significantly correlated with
      gender (P = 0.014), alcohol consumption (P = 0.037), family history (P = 0.019)
      and invasion depth of primary tumor (P = 0.024). Our data suggested that variants
      of ADIPOQ may be genetic markers conferring susceptibility to gastric cancer
      subtypes. These findings need to be validated in a larger panel of samples from
      distinct populations. 

PMID- 23884579
TI  - Soluble ICAM-1 levels in small-cell lung cancer: prognostic value for survival
      and predictive significance for response during chemotherapy.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule, member of the
      immunoglobulin gene superfamily that seems to participate in the evolution of the
      metastatic process. We investigated the significance of baseline soluble ICAM-1
      levels on the outcome of patients with small-cell lung cancer and whether soluble
      ICAM-1 is a predictive marker for objective response during and after
      chemotherapy in patients with small-cell lung cancer. Fifty patients with
      recently diagnosed small-cell lung cancer, as well as 27 healthy smokers, were
      enrolled. Blood samples were collected at the time of diagnosis, during and at
      the end of chemotherapy. Data were correlated with the characteristics of the
      patients and survival as well as with ICAM-1 predictive role for objective
      response. Statistical significant values of baseline soluble ICAM between
      patients and controls (p < 0.001) were observed. Multivariate analysis revealed
      an elevated risk of death of 9 % in the first year after diagnosis for every 10
      units of increased soluble ICAM-1 at the baseline (p = 0.046). Performance status
      and disease stage were also independent prognostic factors. Patients with
      extensive disease who achieved an objective response during chemotherapy showed a
      significant decrease (25.8 %) in their soluble ICAM-1 levels compared with
      baseline levels (p = 0.001). Alongside performance status and disease stage,
      baseline soluble ICAM-1 could be evaluated as an additional prognostic factor in
      patients with small-cell lung cancer. Also, a possible role for soluble ICAM-1
      may exist as a predictive marker for objective response during chemotherapy for
      patients with extensive disease (p = 0.001). 

PMID- 23884580
TI  - Age-period-cohort effect on female breast cancer mortality in Southern Spain.
AB  - Breast cancer is the most common cancer in women worldwide. The analysis of
      breast cancer mortality is needed to plan healthcare systems. This study aims to
      evaluate the age-period-cohort effects on breast cancer mortality in Andalusia
      (Southern Spain) as a whole and in each of its eight provinces during the period
      1981-2008. A population-based ecological study was conducted. In all, 19,707
      deaths from breast cancer were analysed for individuals between the ages of 40
      and 84 years who died in Andalusia in the period of study. A nonlinear regression
      model was estimated for each gender group and geographical area. The effects of
      age, year of death and birth cohort were parameterised using B-spline smoothing
      functions. There is an upward trend in mortality by age until around the age of
      75 years, from which point the trend turned downwards. The analysis of the cohort
      effect reveals a steady fall in breast cancer mortality risk for female
      generations born after 1940. Death rates increased until 1995 and then declined
      until the end of the period. There is an age-period-cohort effect on breast
      cancer mortality similar in all the provinces of Andalusia and for Andalusia as a
      whole. If the current trends continue, it can be expected that these effects will
      continue to reduce female mortality. 

PMID- 23884581
TI  - Elevated risk of opportunistic viral infection in patients with Crohn's disease
      during biological therapies: a meta analysis of randomized controlled trials.
AB  - BACKGROUND: Biological agents have been widely used in the treatment of Crohn's
      disease (CD). These drugs carry the risk of excessive immunosuppression,
      indicating possible opportunistic infections including opportunistic viral
      infections, but no meta analysis has ever focused on this issue. PURPOSE: To
      evaluate whether there is an association between biological agents therapy and
      the risk of opportunistic viral infections and serious infections in patients
      with CD. METHODS: A search of online databases was performed and literature
      selection was carried out according to the inclusion and exclusion criteria by
      reading titles, abstracts and full texts. Study heterogeneity and publication
      bias were assessed. Whether to choose a fixed effects model or a random effects
      model depended on the result of heterogeneity test. RESULTS: There was a
      statistical significance in opportunistic viral infection events between the
      biological agents group and the placebo group. However, our analysis didn't
      observe statistically significant differences between the two groups when
      combined analyses were carried out for herpes zoster and herpes simplex
      separately. A risk trend in the biological agents group was observed in the
      analysis for herpes zoster. More analyses aimed at the outcome measures and
      including influenza and serious infection were carried out separately, but no
      statistical significance was found in them. CONCLUSION: Biological agents use
      might increase the risk of opportunistic viral infections in patients with CD,
      but not the risk of herpes simplex and serious infections. More randomized
      controlled trials (RCTs) are needed to draw the conclusion of whether they could
      elevate the risk of herpes zoster.

PMID- 23884582
TI  - Clinical relevance of information in the Summaries of Product Characteristics for
      dose adjustment in renal impairment.
AB  - PURPOSE: Information about dosing adjustments in patients with chronic kidney
      disease is important to avoid toxicity for several medicines. The aim of our
      study was to assess the clinical relevance of the instructions for dose
      adjustment in patients with renal impairment provided in the Summaries of Product
      Characteristics (SmPCs) approved by the European Medicines Agency (EMA). METHODS:
      SmPCs available on the EMA website on April 2011 were retrieved, and information
      on the elimination route and instructions for use in renal impairment was
      analysed independently by two of the authors. SmPCs were classified as containing
      'explicit' or 'poor' information based on whether they presented (or not)
      instructions for use of the medicine in renal impairment. Information was
      considered 'relevant' if SmPCs provided clear instructions for dose adjustment.
      RESULTS: Of the 356 SmPCs analysed, 13.8 and 37.4 % were classified as providing
      poor information and explicit but not relevant information, respectively. Only
      48.8 % SmPCs provided both explicit and relevant information on medicine use in
      renal impairment. No difference was found in the average time since last update
      among SmPCs classified as containing explicit or poor information, as well as
      those classified as containing relevant or not relevant information. Also, no
      association was found between the clinical relevance of the information and
      whether or not the medication was an orphan drug, and 80 % SmPCs did not provide
      information on the use of the medicine in patients undergoing haemodialysis.
      CONCLUSIONS: Based on our analysis, current versions of SmPCs are characterised
      by several information deficits and by containing recommendations that are not
      relevant to clinical practice in terms of dose adjustment in renal impairment.
      These shortcomings might limit their usefulness for healthcare professionals and
      integration into clinical decision-making support systems.

PMID- 23884583
TI  - Attachment factors.
AB  - As obligate intracellular parasites, viruses must bind to, and enter, permissive
      host cells in order to gain access to the cellular machinery that is required for
      their replication. The very large number of mammalian viruses identified to date
      is reflected in the fact that almost every human and animal cell type is a target
      for infection by one, or commonly more than one, species of virus. As viruses
      have adapted to target certain cell types for their propagation, there is
      exquisite specificity in cellular tropism. This specificity is frequently, but
      not always, mediated by the first step in the viral replication cycle: attachment
      of viral surface proteins to receptors expressed on susceptible cells. Viral
      receptors may be protein, carbohydrate, and/or lipid. Many viruses can use more
      than one attachment receptor, and indeed may sequentially engage multiple
      receptors to infect a cell. Thus, it is useful to differentiate between
      attachment receptors, that simply allow viruses a foothold at the limiting
      membrane of a cell, and entry receptors that mediate delivery the viral genome
      into the cytoplasm. For some viruses the attachment factors that promote binding
      to permissive cells are very well defined, but the sequence of events that
      triggers viral entry is only now beginning to be understood. For other viruses,
      despite many efforts, the receptors remain elusive. In this chapter we will
      confine our review to viruses that infect mammals, with particular focus on human
      pathogens. We do not intend that this will be an exhaustive overview of viral
      attachment receptors; instead we will take a number of examples of well
      characterized virus-receptor interactions, discuss supporting evidence, and
      highlight any controversies and uncertainties in the field. We will then conclude
      with a reflection on general principles of viral attachment, consider some
      exceptions to these principles, and make some suggestion for future research. 

PMID- 23884584
TI  - Picornavirus entry.
AB  - The essential event in picornavirus entry is the delivery of the RNA genome to
      the cytoplasm of a target cell, where replication occurs. In the past several
      years progress has been made in understanding the structural changes in the
      virion important for uncoating and RNA release. In addition, for several viruses
      the endocytic mechanisms responsible for internalization have been identified, as
      have the cellular sites at which uncoating occurs. It has become clear that entry
      is not a passive process, and that viruses initiate specific signals required for
      entry. And we have begun to recognize that for a given virus, there may be
      multiple routes of entry, depending on the particular target cell and the
      receptors available on that cell. 

PMID- 23884586
TI  - Entry of influenza virus.
AB  - As a major pathogen of human and certain animal species, influenza virus causes
      wide spread and potentially devastating disease. To initiate infection, the virus
      first binds to cellular receptors comprising either -(2,3 ) or -(2,6) linked
      sialic acid. Recent advances in our understanding of the influenza virus receptor
      and viral host species involved have shed light on the molecular mechanism of how
      influenza virus transmits across species and adapts to a new host. Following
      receptor binding, influenza viruses are internalized through multiple endocytic
      pathways, including both clathrin- and non-clathrin-dependent routes, which have
      recently been visualized at single viral particle level. The viral envelope then
      fuses with the endosomal membrane in a low pH-dependent manner and the viral
      genome is released into the cytosol, followed by further transport to the nucleus
      where genome replication occurs.

PMID- 23884587
TI  - Filovirus entry.
AB  - A number of advances in recent years have significantly furthered our
      understanding of filovirus attachment and cellular tropism. For example, several
      cell-surface molecules have been identified as attachment factors with the
      potential to facilitate the in vivo targeting of particular cell types such as
      macrophages and hepatic cells. Furthermore, our knowledge of internalization and
      subsequent events during filovirus entry has also been widened, adding new
      variations to the paradigms for viral entry established for HIV and influenza. In
      particular, host cell factors such as endosomal proteases and the intracellular
      receptor Niemann-Pick C1 are now known to play a vital role in activating the
      membrane fusion potential of filovirus glycoproteins. 

PMID- 23884588
TI  - Paramyxovirus entry.
AB  - The family Paramyxoviridae consists of a group of large, enveloped, negative
      sense, single-stranded RNA viruses and contains many important human and animal
      pathogens. Molecular and biochemical characterization over the past decade has
      revealed an extraordinary breadth of biological diversity among this family of
      viruses. Like all enveloped viruses, paramyxoviruses must fuse their membrane
      with that of a receptive host cell as a prerequisite for viral entry and
      infection. Unlike most other enveloped viruses, the vast majority of
      paramyxoviruses contain two distinct membrane-anchored glycoproteins to mediate
      the attachment, membrane fusion and particle entry stages of host cell infection.
      The attachment glycoprotein is required for virion attachment and the fusion
      glycoprotein is directly involved in facilitating the merger of the viral and
      host cell membranes. Here we detail important functional, biochemical and
      structural features of the attachment and fusion glycoproteins from a variety of
      family members. Specifically, the three different classes of attachment
      glycoproteins are discussed, including receptor binding preference, their overall
      structure and fusion promotion activities. Recently solved atomic structures of
      certain attachment glycoproteins are summarized, and how they relate to both
      receptor binding and fusion mechanisms are described. For the fusion
      glycoprotein, specific structural domains and their proposed role in mediating
      membrane merger are illustrated, highlighting the important features of protease
      cleavage and associated tropism and virulence. The crystal structure solutions of
      both an uncleaved and a cleavage-activated metastable F are also described with
      emphasis on how small conformational changes can provide the necessary energy to
      mediate membrane fusion. Finally, the different proposed fusion models are
      reviewed, featuring recent experimental findings that speculate how the
      attachment and fusion glycoproteins work in concert to mediate virus entry.

PMID- 23884589
TI  - Cellular entry of retroviruses.
AB  - The retrovirus family contains several important human and animal pathogens,
      including the human immunodeficiency virus (HIV), the causative agent of acquired
      immunodeficiency syndrome (AIDS). Studies with retroviruses were instrumental to
      our present understanding of the cellular entry of enveloped viruses in general.
      For instance, studies with alpharetroviruses defined receptor engagement, as
      opposed to low pH, as a trigger for the envelope protein-driven membrane fusion.
      The insights into the retroviral entry process allowed the generation of a new
      class of antivirals, entry inhibitors, and these therapeutics are at present used
      for treatment of HIV/AIDS. In this chapter, we will summarize key concepts
      established for entry of avian sarcoma and leukosis virus (ASLV), a widely used
      model system for retroviral entry. We will then review how foamy virus and HIV,
      primate- and human retroviruses, enter target cells, and how the interaction of
      the viral and cellular factors involved in the cellular entry of these viruses
      impacts viral tropism, pathogenesis and approaches to therapy and vaccine
      development. 

PMID- 23884585
TI  - Reovirus receptors, cell entry, and proapoptotic signaling.
AB  - Mammalian orthoreoviruses (reoviruses) are members of the Reoviridae. Reoviruses
      contain 10 double-stranded (ds) RNA gene segments enclosed in two concentric
      protein shells, called outer capsid and core. These viruses serve as a versatile
      experimental system for studies of viral replication events at the virus-cell
      interface, including engagement of cell-surface receptors, internalization and
      disassembly, and activation of the innate immune response, including NF-kappaB
      dependent cellular signaling pathways. Reoviruses also provide a model system for
      studies of virus-induced apoptosis and organ-specific disease in vivo.Reoviruses
      attach to host cells via the filamentous attachment protein, sigma1. The sigma1
      protein of all reovirus serotypes engages junctional adhesion molecule-A (JAM-A),
      an integral component of intercellular tight junctions. The sigma1 protein also
      binds to cell-surface carbohydrate, with the type of carbohydrate bound varying
      by serotype. Following attachment to JAM-A and carbohydrate, reovirus
      internalization is mediated by beta1 integrins, most likely via clathrin
      dependent endocytosis. In the endocytic compartment, reovirus outer-capsid
      protein sigma3 is removed by acid-dependent cysteine proteases in most cell
      types. Removal of sigma3 results in the exposure of a hydrophobic conformer of
      the viral membrane-penetration protein, MU1, which pierces the endosomal membrane
      and delivers transcriptionally active reovirus core particles into the
      cytoplasm.Reoviruses induce apoptosis in both cultured cells and infected mice.
      Perturbation of reovirus disassembly using inhibitors of endosomal acidification
      or protease activity abrogates apoptosis. The MU1-encoding M2 gene is genetically
      linked to strain-specific differences in apoptosis-inducing capacity, suggesting
      a function for MU1 in induction of death signaling. Reovirus disassembly leads to
      activation of transcription factor NF-kappaB, which modulates apoptotic signaling
      in numerous types of cells. Inhibition of NF-kappaB nuclear translocation using
      either pharmacologic agents or expression of transdominant forms of IkappaB
      blocks reovirus-induced apoptosis, suggesting an essential role for NF-kappaB
      activation in the death response. Multiple effector pathway s downstream of NF
      kappaB-directed gene expression execute reovirus-induced cell death. This chapter
      will focus on the mechanisms by which reovirus attachment and disassembly
      activate NF-kappaB and stimulate the cellular proapoptotic machinery. 

PMID- 23884590
TI  - Class II fusion proteins.
AB  - Enveloped viruses rely on fusion proteins in their envelope to fuse the viral
      membrane to the host-cell membrane. This key step in viral entry delivers the
      viral genome into the cytoplasm for replication. Although class II fusion
      proteins are genetically and structurally unrelated to class I fusion proteins,
      they use the same physical principles and topology as other fusion proteins to
      drive membrane fusion. Exposure of a fusion loop first allows it to insert into
      the host-cell membrane. Conserved hydrophobic residues in the fusion loop act as
      an anchor, which penetrates only partway into the outer bilayer leaflet of the
      host-cell membrane. Subsequent folding back of the fusion protein on itself
      directs the C-terminal viral transmembrane anchor towards the fusion loop. This
      fold-back forces the host-cell membrane (held by the fusion loop) and the viral
      membrane (held by the C-terminal transmembrane anchor) against each other,
      resulting in membrane fusion. In class II fusion proteins, the fold-back is
      triggered by the reduced pH of an endosome, and is accompanied by the assembly of
      fusion protein monomers into trimers. The fold-back occurs by domain
      rearrangement rather than by an extensive refolding of secondary structure, but
      this domain rearrangement and the assembly of monomers into trimers together bury
      a large surface area. The energy that is thus released exerts a bending force on
      the apposed viral and cellular membranes, causing them to bend towards each other
      and, eventually, to fuse. 

PMID- 23884591
TI  - Entry of rhabdoviruses into animal cells.
AB  - Entry is the first step in the infectious life cycle of a virus. In the case of
      rhabdoviruses, entry is facilitated exclusively by the envelope glycoprotein G
      and its interactions with the host cell. For vesicular stomatitis virus (VSV),
      attachment to the cell surface was thought to be facilitated by interactions with
      the lipid phosphatidylserine, however recent work suggests that it is in fact
      initiated by recognition of proteinaeous receptors. Clathrin-mediated endocytosis
      delivers the virions into endosomes where they have been proposed to traffic to
      multi-vesicular bodies. There, the viral envelope fuses with internal vesicles in
      a process mediated by glycoprotein G in a pH- and phosphatidylserine-dependent
      manner. A clear mechanistic understanding of glycoprotein G mediated fusion has
      yet to be obtained, however current data suggests that it is likely facilitated
      by events distinct from Class I or Class II fusion proteins of other viruses.
      Rhabdoviruses are also notable in that their fusion protein exists in a
      reversible pH-dependent equilibrium, which prevents irreversible preactivation
      during assembly, and may prove to be relevant in the mediation of cell-to-cell
      fusion - an alternate form of viral spread. 

PMID- 23884592
TI  - Entry of herpesviruses into cells: the enigma variations.
AB  - The entry of herpesviruses into their target cells is complex at many levels.
      Virus entry proceeds by a succession of interactions between viral envelope
      glycoproteins and molecules on the cell membrane. The process is divided into
      distinct steps: attachment to the cell surface, interaction with a specific entry
      receptor, internalization of the particle (optional and cell specific), and
      membrane fusion. Several viral envelope glycoproteins are involved in one or
      several of these steps. The most conserved entry glycoproteins in the herpesvirus
      family (gB, gH/gL) are involved in membrane fusion. Around this functional core,
      herpesviruses have a variety of receptor binding glycoproteins, which interact
      with cell surface proteins often from different families. This interaction
      activates and controls the actual fusion machinery. Interactions with cellular
      receptors and between viral glycoproteins have to be tightly coordinated and
      regulated to guarantee successful entry. Although additional entry receptors for
      herpesviruses continue to be identified, the molecular interactions between viral
      glycoproteins remain mostly enigmatic. This chapter will review our current
      understanding of the molecular interactions that occur during herpesvirus entry
      from attachment to fusion. Particular emphasis will be placed on structure-based
      representation of receptor binding as a trigger of fusion during herpes simplex
      virus entry. 

PMID- 23884593
TI  - Mutational analysis of cj0183 Campylobacter jejuni promoter.
AB  - Gene-nominated cj0183 was identified in Campylobacter jejuni NCTC 11168 and in
      two human isolates 81116 and 81-176. It encodes a protein which shows partial
      homology to TlyC of Brachyspira hyodysenteriae. The aim of this work was to
      determine the mechanisms of gene regulation by cloning DNA fragments lying
      upstream of the cj0183 gene. The beta-galactosidase activity determined for the
      strain harboring the plasmid with the fragment upstream of cj0183 indicated the
      presence of a promoter in this DNA region. Mutations in cj0183 -10 region, -16
      region, and -35 region resulted in changes in gene transcription. 

PMID- 23884594
TI  - Molecular detection of HpmA and HlyA hemolysin of uropathogenic Proteus
      mirabilis.
AB  - Urinary tract infection (UTI) is one of the bacterial infections frequently
      documented in humans. Proteus mirabilis is associated with UTI mainly in
      individuals with urinary tract abnormality or related with vesicular catheterism
      and it can be difficult to treat because of the formation of stones in the
      bladder and kidneys. These stones are formed due to the presence of urease
      synthesized by the bacteria. Another important factor is that P. mirabilis
      produces hemolysin HpmA, used by the bacteria to damage the kidney tissues.
      Proteus spp. samples can also express HlyA hemolysin, similar to that found in
      Escherichia coli. A total of 211 uropathogenic P. mirabilis isolates were
      analyzed to detect the presence of the hpmA and hpmB genes by the techniques of
      polymerase chain reaction (PCR) and dot blot and hlyA by PCR. The hpmA and hpmB
      genes were expressed by the RT-PCR technique and two P. mirabilis isolates were
      sequenced for the hpmA and hpmB genes. The presence of the hpmA and hpmB genes
      was confirmed by PCR in 205 (97.15 %) of the 211 isolates. The dot blot confirmed
      the presence of the hpmA and hpmB genes in the isolates that did not amplify in
      the PCR. None of the isolates studied presented the hlyA gene. The hpmA and hpmB
      genes that were sequenced presented 98 % identity with the same genes of the
      HI4320 P. mirabilis sample. This study showed that the PCR technique has good
      sensitivity for detecting the hpmA and hpmB genes of P. mirabilis.

PMID- 23884595
TI  - Improvement of manganese peroxidase production by the hyper lignin-degrading
      fungus Phanerochaete sordida YK-624 by recombinant expression of the 5
      aminolevulinic acid synthase gene.
AB  - The manganese peroxidase (MnP) gene (mnp4) promoter of Phanerochaete sordida YK
      624 was used to drive expression of 5-aminolevulinic acid synthase (als), which
      is a key heme biosynthesis enzyme. The expression plasmid pMnP4pro-als was
      transformed into P. sordida YK-624 uracil auxotrophic mutant UV-64, and 14
      recombinant als expressing-transformants were generated. Average cumulative MnP
      activities in the transformants were 1.18-fold higher than that of control
      transformants. In particular, transformants A-14 and A-61 showed significantly
      higher MnP activity (approximately 2.8-fold) than wild type. RT-PCR analysis
      indicated that the increased MnP activity was caused by elevated recombinant als
      expression. These results suggest that the production of MnP is improved by high
      expression of als. 

PMID- 23884596
TI  - Early predictors of not returning to work in low-income breast cancer survivors:
      a 5-year longitudinal study.
AB  - Low-income women may be especially vulnerable to job loss after a breast cancer
      diagnosis. The identification of early risk factors for not returning to work in
      the long term could inform interventions to help survivors avoid this outcome. A
      consecutive sample of low-income, employed, underinsured/uninsured women treated
      for stage 0-III breast cancer was surveyed 6, 18, 36, and 60 months after
      diagnosis. Participants were classified according to the survey in which they
      first reported return to work. If they were not working in every survey they were
      classified as not returning to work. Correlates of not returning to work were
      identified. Of 274 participants, 36 % returned to work by 6 months, an additional
      21 % by 18, 10 % by 36, and 5 % by 60 months. 27 % never returned to work. Of
      those not working at 6 months, 43 % never returned. Independent predictors of
      never returning to work included lowest annual income (<$10,000), Latina
      ethnicity, high comorbidity burden, and receipt of chemotherapy. Very poor women
      who stop working during chemotherapy for breast cancer are at risk of not
      returning to work months and years following treatment. These findings may have
      clinical and policy implications. Conversely, radiation therapy, axillary node
      dissection, age, and job type do not appear to be associated with return to work.
      Clinicians should discuss work-related concerns with patients and facilitate
      early return to work when desired by the patient. Additional research is needed
      to develop interventions to optimize return to work. 

PMID- 23884597
TI  - Comparison of efficacy of 95-gene and 21-gene classifier (Oncotype DX) for
      prediction of recurrence in ER-positive and node-negative breast cancer patients.
AB  - We recently developed a 95-gene classifier (95(GC)) for the prognostic prediction
      for ER-positive and node-negative breast cancer patients treated with only
      adjuvant hormonal therapy. The aim of this study was to validate the efficacy of
      95(GC) and compare it with that of 21(GC) (Oncotype DX) as well as to evaluate
      the combination of 95(GC) and 21(GC). DNA microarray data (gene expression) of ER
      positive and node-negative breast cancer patients (n = 459) treated with adjuvant
      hormone therapy alone as well as those of ER-positive breast cancer patients
      treated with neoadjuvant chemotherapy (n = 359) were classified with 95(GC) and
      21(GC) (Recurrence Online at http://www.recurrenceonline.com/ ). 95(GC)
      classified the 459 patients into low-risk (n = 285; 10 year relapse-free
      survival: 88.8 %) and high-risk groups (n = 174; 70.6 %) (P = 5.5e-10), and
      21(GC) into low-risk group (n = 286; 89.3 %), intermediate-risk (n = 81; 75.7 %),
      and high-risk (n = 92; 64.7 %) groups (P = 2.9e-10). The combination of 95(GC)
      and 21(GC) classified them into low-risk (n = 324; 88.9 %) and high-risk (n =
      135; 65.0 %) groups (P = 5.9e-14), and also showed that pathological complete
      response rates were significantly (P = 2.5e-6) higher for the high-risk (17.9 %)
      than the low-risk group (3.6 %). In addition, we demonstrated that 95(GC) was
      calculated on a single-sample basis if the reference robust multi-array average
      workflow was used for normalization. The prognostic prediction capability of
      95(GC) appears to be comparable to that of 21(GC). Moreover, their combination
      seems to result in the identification of more low-risk patients who do not need
      chemotherapy than either classification alone. The patients in the high-risk
      group were found to be more chemo-sensitive so that they can benefit more from
      adjuvant chemotherapy. 

PMID- 23884598
TI  - The detection of QTLs in barley associated with endosperm hardness, grain
      density, grain size and malting quality using rapid phenotyping tools.
AB  - Using a barley mapping population, 'Vlamingh' * 'Buloke' (V * B), whole grain
      analyses were undertaken for physical seed traits and malting quality. Grain
      density and size were predicted by digital image analysis (DIA), while malt
      extract and protein content were predicted using near infrared (NIR) analysis.
      Validation of DIA and NIR algorithms confirmed that data for QTL analysis was
      highly correlated (R (2) > 0.82), with high RPD values (the ratio of the standard
      error of prediction to the standard deviation, 2.31-9.06). Endosperm hardness was
      measured on this mapping population using the single kernel characterisation
      system. Grain density and endosperm hardness were significantly inter-correlated
      in all three environments (r > 0.22, P < 0.001); however, other grain components
      were found to interact with the traits. QTL for these traits were also found on
      different genomic regions, for example, grain density QTLs were found on
      chromosomes 2H and 6H, whereas endosperm hardness QTLs were found on 1H, 5H, and
      7H. In this study, the majority of the genomic regions associated with grain
      texture were also coincident with QTLs for grain size, yield, flowering date
      and/or plant development genes. This study highlights the complexity of genomic
      regions associated with the variation of endosperm hardness and grain density,
      and their relationships with grain size traits, agronomic-related traits, and
      plant development loci. 

PMID- 23884599
TI  - Genetics of tan spot resistance in wheat.
AB  - Tan spot is a devastating foliar disease of wheat caused by the necrotrophic
      fungal pathogen Pyrenophora tritici-repentis. Much has been learned during the
      past two decades about the genetics of wheat-P. tritici-repentis interactions.
      Research has shown that the fungus produces at least three host-selective toxins
      (HSTs), known as Ptr ToxA, Ptr ToxB, and Ptr ToxC, that interact directly or
      indirectly with the products of the dominant host genes Tsn1, Tsc2, and Tsc1,
      respectively. The recent cloning and characterization of Tsn1 provided strong
      evidence that the pathogen utilizes HSTs to subvert host resistance mechanisms to
      cause disease. However, in addition to host-HST interactions, broad-spectrum,
      race non-specific resistance QTLs and recessively inherited qualitative
      'resistance' genes have been identified. Molecular markers suitable for marker
      assisted selection against HST sensitivity genes and for race non-specific
      resistance QTLs have been developed and used to generate adapted germplasm with
      good levels of tan spot resistance. Future research is needed to identify novel
      HSTs and corresponding host sensitivity genes, determine if the recessively
      inherited resistance genes are HST insensitivities, extend the current race
      classification system to account for new HSTs, and determine the molecular basis
      of race non-specific resistance QTLs and their relationships with host-HST
      interactions at the molecular level. Necrotrophic pathogens such as P. tritici
      repentis are likely to become increasingly significant under a changing global
      climate making it imperative to further characterize the wheat-P. tritici
      repentis pathosystem and develop tan spot resistant wheat varieties. 

PMID- 23884600
TI  - Genome-wide association analysis for nine agronomic traits in maize under well
      watered and water-stressed conditions.
AB  - Drought can cause severe reduction in maize production, and strongly threatens
      crop yields. To dissect this complex trait and identify superior alleles, 350
      tropical and subtropical maize inbred lines were genotyped using a 1536-SNP array
      developed from drought-related genes and an array of 56,110 random SNPs. The
      inbred lines were crossed with a common tester, CML312, and the testcrosses were
      phenotyped for nine traits under well-watered and water-stressed conditions in
      seven environments. Using genome-wide association mapping with correction for
      population structure, 42 associated SNPs (P <= 2.25 * 10(-6) 0.1/N) were
      identified, located in 33 genes for 126 trait * environment * treatment
      combinations. Of these genes, three were co-localized to drought-related QTL
      regions. Gene GRMZM2G125777 was strongly associated with ear relative position,
      hundred kernel weight and timing of male and female flowering, and encodes NAC
      domain-containing protein 2, a transcription factor expressed in different
      tissues. These results provide some good information for understanding the
      genetic basis for drought tolerance and further studies on identified candidate
      genes should illuminate mechanisms of drought tolerance and provide tools for
      designing drought-tolerant maize cultivars tailored to different environmental
      scenarios. 

PMID- 23884601
TI  - Large deletions in the CBF gene cluster at the Fr-B2 locus are associated with
      reduced frost tolerance in wheat.
AB  - Wheat plants which are exposed to periods of low temperatures (cold acclimation)
      exhibit increased survival rates when they are subsequently exposed to freezing
      temperatures. This process is associated with large-scale changes in the
      transcriptome which are modulated by a set of tandemly duplicated C-repeat
      Binding Factor (CBF) transcription factors located at the Frost Resistance-2 (Fr
      2) locus. While Arabidopsis has three tandemly duplicated CBF genes, the CBF
      family in wheat has undergone an expansion and at least 15 CBF genes have been
      identified, 11 of which are present at the Fr-2 loci on homeologous group 5
      chromosomes. We report here the discovery of three large deletions which
      eliminate 6, 9, and all 11 CBF genes from the Fr-B2 locus in tetraploid and
      hexaploid wheat. In wild emmer wheat, the Fr-B2 deletions were found only among
      the accessions from the southern sub-populations. Among cultivated wheats, the Fr
      B2 deletions were more common among varieties with a spring growth habit than
      among those with a winter growth habit. Replicated freezing tolerance experiments
      showed that both the deletion of nine CBF genes in tetraploid wheat and the
      complete Fr-B2 deletion in hexaploid wheat were associated with significant
      reductions in survival after exposure to freezing temperatures. Our results
      suggest that selection for the wild-type Fr-B2 allele may be beneficial for
      breeders selecting for varieties with improved frost tolerance. 

PMID- 23884602
TI  - Late-onset bleb-related endophthalmitis caused by Streptococcus pseudopneumoniae.
AB  - We report our findings in a 63-year-old male who developed late-onset bleb
      related endophthalmitis. The patient had undergone glaucoma surgery 46 years
      earlier, and had a thin-walled cystic bleb prior to the endophthalmitis in his
      right eye. He underwent immediate vitrectomy with intravitreal injections of
      ceftazidime and vancomycin. After surgery, he was given topical 0.5 %
      moxifloxacin and 1 % vancomycin, intravenous doripenem, and oral minocycline.
      Culture of the vitreous specimen identified Streptococcus pseudopneumoniae by 16S
      rRNA sequence analysis, by optochin susceptibility test, and by bile solubility
      test. Our findings indicate that S. pseudopneumoniae can be isolated from a late
      onset bleb-related endophthalmitis and that molecular analysis and phenotypic
      testing can be accurate methods to identify S. pseudopneumoniae.

PMID- 23884603
TI  - Pharmaceutical sales representatives and patient safety.

PMID- 23884604
TI  - Assessment of the association between XRCC1 Arg399Gln polymorphism and lung
      cancer in Chinese.
AB  - X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair
      proteins involved in the base excision repair and plays an important role in the
      maintenance of genomic integrity. Polymorphisms in XRCC1 may alter the function
      and repair capacity of XRCC1 protein which further results in the genetic
      instability and lung carcinogenesis. Previous studies investigating the
      relationship between XRCC1 Arg399Gln polymorphism and lung cancer risk in Chinese
      yielded contradictory results. A meta-analysis was performed to clarify the
      effect of XRCC1 Arg399Gln polymorphism on lung cancer. The association was
      assessed by calculating the pooled odds ratio (OR) with 95% confidence intervals
      (95%CI). Nineteen studies with a total of 12,835 participants were included into
      this meta-analysis. Overall, there was an obvious association between XRCC1
      Arg399Gln polymorphism and increased risk of lung cancer under three genetic
      models (Gln vs. Arg: OR = 1.13, 95%CI 1.01-1.25, P = 0.029; GlnGln vs. ArArg: OR
      = 1.41, 95%CI 1.07-1.84, P = 0.013; GlnGln vs. ArArg/ArgGln: OR = 1.37, 95%CI
      1.07-1.76, P = 0.013). Meta-analysis of 18 studies with high quality also found
      that there was an obvious association between XRCC1 Arg399Gln polymorphism and
      increased risk of lung cancer under three genetic models. There was no obvious
      risk of bias in the meta-analysis. Data from the current meta-analysis support
      the obvious association between XRCC1 Arg399Gln polymorphism and increased risk
      of lung cancer in Chinese.

PMID- 23884605
TI  - Association between glutathione S-transferase M 1 null genotype and risk of
      ovarian cancer: a meta-analysis.
AB  - Though previous studies investigated the association between glutathione S
      transferase M 1 (GSTM1) null genotype and ovarian cancer risk, the effect of
      GSTM1 null genotype on ovarian cancer risk was still unclear. To comprehensively
      quantify the association between GSTM1 null genotype and ovarian cancer risk, we
      performed a meta-analysis. Eleven studies from ten publications were identified
      from PubMed database. The pooled odds ratio (OR) with its 95% confidence interval
      (CI) was used to assess the association. Meta-analysis of the total 11 studies
      showed that GSTM1 null genotype was not associated with ovarian cancer risk (OR =
      1.03, 95% CI 0.92-1.14, P = 0.625). The cumulative meta-analyses showed a trend
      of no association between GSTM1 null genotype and ovarian cancer risk as
      information accumulated by year. There was no evidence of publication bias in the
      meta-analysis. Meta-analysis of the 11 available studies shows that GSTM1 null
      genotype is not associated with ovarian cancer risk.

PMID- 23884606
TI  - Impaired replication elongation in Tetrahymena mutants deficient in histone H3
      Lys 27 monomethylation.
AB  - Replication of nuclear DNA occurs in the context of chromatin and is influenced
      by histone modifications. In the ciliate Tetrahymena thermophila, we identified
      TXR1, encoding a histone methyltransferase. TXR1 deletion resulted in severe DNA
      replication stress, manifested by the accumulation of ssDNA, production of
      aberrant replication intermediates, and activation of robust DNA damage
      responses. Paired-end Illumina sequencing of ssDNA revealed intergenic regions,
      including replication origins, as hot spots for replication stress in DeltaTXR1
      cells. DeltaTXR1 cells showed a deficiency in histone H3 Lys 27 monomethylation
      (H3K27me1), while DeltaEZL2 cells, deleting a Drosophila E(z) homolog, were
      deficient in H3K27 di- and trimethylation, with no detectable replication stress.
      A point mutation in histone H3 at Lys 27 (H3 K27Q) mirrored the phenotype of
      DeltaTXR1, corroborating H3K27me1 as a key player in DNA replication.
      Additionally, we demonstrated interactions between TXR1 and proliferating cell
      nuclear antigen (PCNA). These findings support a conserved pathway through which
      H3K27me1 facilitates replication elongation. 

PMID- 23884607
TI  - Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant
      TH2B.
AB  - The conversion of male germ cell chromatin to a nucleoprotamine structure is
      fundamental to the life cycle, yet the underlying molecular details remain
      obscure. Here we show that an essential step is the genome-wide incorporation of
      TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in
      which TH2B is depleted or C-terminally modified, we show that TH2B directs the
      final transformation of dissociating nucleosomes into protamine-packed
      structures. Depletion of TH2B induces compensatory mechanisms that permit histone
      removal by up-regulating H2B and programming nucleosome instability through
      targeted histone modifications, including lysine crotonylation and arginine
      methylation. Furthermore, after fertilization, TH2B reassembles onto the male
      genome during protamine-to-histone exchange. Thus, TH2B is a unique histone
      variant that plays a key role in the histone-to-protamine packing of the male
      genome and guides genome-wide chromatin transitions that both precede and follow
      transmission of the male genome to the egg. 

PMID- 23884608
TI  - Deep-tissue photoacoustic tomography of Forster resonance energy transfer.
AB  - Forster resonance energy transfer (FRET) is a distance-dependent process that
      transfers excited state energy from a donor molecule to an acceptor molecule
      without the emission of a photon. The FRET rate is determined by the proximity
      between the donor and the acceptor molecules; it becomes significant only when
      the proximity is within several nanometers. Therefore, FRET has been applied to
      visualize interactions and conformational changes of biomolecules, such as
      proteins, lipids, and nucleic acids that cannot be resolved by optical
      microscopy. Here, we report photoacoustic tomography of FRET efficiency at a 1-cm
      depth in chicken breast tissue, whereas conventional high-resolution fluorescence
      imaging is limited to <0.1  cm. Photoacoustic tomography is expected to
      facilitate the examination of FRET phenomena in living organisms.

PMID- 23884609
TI  - Evaluation of the impact of pharmaceutical care service on hospitalized patients
      with chronic kidney disease in Jordan.
AB  - OBJECTIVES: The primary goal of the present study was to implement and evaluate
      the impact of pharmaceutical care service for hospitalized chronic kidney disease
      (CKD) patients in Jordan. SETTING: Nephrology wards of one of the largest general
      hospitals in Jordan. METHODS: All patients who were previously diagnosed with CKD
      by their physician were eligible for inclusion in the study. Recruited patients
      were fully assessed for treatment related problems (TRPs) by a clinical
      pharmacist. Pharmaceutical care service was assessed through a systematic,
      prospective before-after design. Chi Square test was used to investigate
      association between categorical variables. P value <0.05 was considered to be
      statistically significant. MAIN OUTCOME MEASURES: Study outcomes included:
      Process outcomes (prevalence and nature of identified TRPs, clinical significance
      of TRPs, associated diseases and drugs), General clinical outcomes (Therapeutic
      outcomes of TRPs) and CKD specific clinical outcomes (Change from baseline in the
      number of patients receiving appropriate progression modifying therapy and
      appropriate management of complications). RESULTS: 130 patients were included in
      the study. The average number of the identified TRPs was 5.31. Eighty-six percent
      of the recommendations were accepted by physicians. Efficacy related problems
      were the most common TRP category. Seventeen percent of all TRPs were resolved,
      5.5 % were improved, and 37.4 % were prevented through the clinical pharmacist
      interventions. CONCLUSIONS: The current study indicated that hospitalized
      patients with CKD suffer from multiple TRPs mostly related to efficacy of
      medications and patients monitoring. Clinical pharmacists substantially
      contributed towards the care of hospitalized CKD patients through optimizing
      progression modifying therapies, medications safety and management of CKD
      complications. Based on this study it is strongly recommended to implement
      pharmaceutical care services for hospitalized CKD patients.

PMID- 23884611
TI  - Microvascular decompression for neurovascular conflicts in the cerebello-pontine
      angle: which role for endoscopy?
AB  - BACKGROUND: Microvascular decompression (MVD) is the surgical intervention
      designed to resolve neurovascular conflicts (NCs) in the cerebellopontine angle
      (CPA). Today, endoscopy is commonly used in many neurosurgical procedures. This
      study aims to retrospectively assess the usefulness of endoscopy during MVD,
      focusing on microscopic endoscopic-assisted (MEA) MVD. METHODS: Between January
      2010 and December 2012, 141 patients underwent MVD procedures: 119 (84.5 %) were
      affected by idiopathic trigeminal neuralgia (TN), 20 (14 %) by hemifacial spasm
      (HFS), 1 by glossopharyngeal neuralgia (GN) and 1 by TN and GN simultaneously;
      128 (91 %) MVD were first time procedures, while 13 (9 %) were recurrences (10
      TN, 3 HFS). Visualization techniques used were: pure microscopic in 89 (63 %)
      cases, fully endoscopic in 12 (8.5 %) and MEA in 40 (28.5 %). The MEA technique
      was used when the conflict was not clearly identified under microscopic view or
      it was not certainly resolved. RESULTS: Overall, a NC was found in 130 (92 %)
      cases, while 11 patients had no intraoperative evidence of NC. Considering
      specifically the 40 MEA cases, 12 (8.5 % overall) conflicts not clearly visible
      with the microscope were revealed and solved, a complete conflict resolution was
      confirmed in 13 (9 % overall) cases, while an incomplete conflict resolution was
      shown in four cases (3 % overall). CONCLUSION: Pure microscopic MVD remains the
      technique of choice. The endoscope is a useful adjunctive imaging tool in
      confirming NCs identified by the microscope, revealing conflicts missed by the
      microscopic survey alone and verifying adequate nerve decompression.

PMID- 23884612
TI  - [Factors associated with hospital admission and evaluation of a case management
      program for severe mental disorder by a historical cohort study].
AB  - INTRODUCTION: People with severe mental disorder (SMD) have serious difficulties
      in developing a normal life, so community care programs to improve their living
      conditions and social integration are necessary. This work evaluates the
      performance of a case management program (CMP) in Segovia (Spain). METHODOLOGY:
      We conduct a first descriptive phase evaluating the performance of the CMP in
      2011 by sociodemographic, health services and clinical variables. We study the
      factors associated with the occurrence of hospital admission. Finally, using a
      historical cohort design, we assess the risk of hospital admission of CMP
      compared to unexposed cohort. Bi and multivariate statistical techniques are
      employed to perform the analysis with the calculation of relative risks and
      confidence intervals. RESULTS: In 2011, 82 patients are cared for in the CMP,
      mainly middle-aged men. The average clinical course is 19 years and the average
      stay in the CMP over 6 years. 78% belong to the diagnosis of schizophrenia
      spectrum. Income affects 27% of patients. Women, mental health teams I-II,
      increased home visits and abandonment of monitoring are predictors of income,
      while the highest level of clinical course is protective. No protective effect of
      income is detected for the CMP in the different analyzes of the historical cohort
      study. CONCLUSIONS: It is necessary to systematically assess community care
      programs directed at SMD to make adjustments and modifications aiming at
      improving their clinical effectiveness.

PMID- 23884613
TI  - [Prevalence and factors associated to mental disorders in primary care attenders
      aged 75 and older].
AB  - BACKGROUND: Mental disorders in old age are a major public health problem.
      However, few epidemiological studies provide data on prevalence and risk factors
      of mental illness in older old population. The aim of this study is to assess the
      prevalence of common mental disorders and their associated factors in primary
      care patients over 75 years. METHOD: Cross-sectional epidemiologic study carried
      out in a sample of 426 older old patients who were attended at Primary Health
      Care settings, proportionally distributed for provinces and health centers. The
      Spanish version of the Primary Care Evaluation of Mental Disorders (PRIME-MD) was
      used in order to diagnose the most common psychiatric disorders in this field.
      RESULTS: Prevalence and comorbidity rates of affective, anxiety and somatoform
      disorders are high. 47.4% of the sample presented one or more psychiatric
      disorder. The most prevalent were affective (33.8%), somatoform (24.4%) and
      anxiety (14.3%) disorders. 6.3% had comorbidity between affective, anxiety and
      somatoform disorders. Perceived health status and physical illnesses were
      significantly associated with these mental disorders. CONCLUSIONS: Affective,
      anxiety and somatoform disorders are highly prevalent in older old population
      with high rates of comorbidity. Their detection and treatment should be
      considered a relevant issue in primary care.

PMID- 23884614
TI  - [Translation into Spanish and validation of the Snaith-Hamilton Pleasure Scale
      (SHAPS) for anhedonia].
AB  - INTRODUCTION: The inability to experience pleasure, anhedonia, is recognized as
      al hallmark symptom of depression. A 14-item, self-report scale developed for the
      assessment of hedonic capacity: the Snaith-Hamilton Pleasure Scale (SHAPS) has
      proved to be a reliable and valid psychometric instrument. OBJECTIVE: Because
      there are no versions of the scale in other languages, our objective in this
      study was to translate the instrument into spanish and to determine if the new
      version maintained the validity and reliability of its original english version.
      METHODOLOGY: The scale was translated into spanish and after reaching final
      consensus applied to a group of depressed patients participating in a
      pharmacological trial. The Hamilton Depression Rating Scale (HDRS) was also
      applied for comparative purposes. RESULTS: Our results demonstrate that the SHAPS
      in its spanish version maintains the validity and reliability level of the
      original english version. A moderate internal consistency was determined by
      Cronbach alpha value of 0.77. CONCLUSION: our results demonstrate the the spanish
      version of the SHAPS has validity and reliability similar to its original
      version, and thus it represents a good alternative to evaluate anhedonia in
      spanish-speaking populations.

PMID- 23884615
TI  - [Environmental and genetic factors associated with psychoactive medication use in
      adult females. A population-based twin study].
AB  - INTRODUCTION: Our objective is to determine the prevalence and factors associated
      to psychotropic medication consumption in a sample of adult females.
      Additionally, this study seeks to analyze the relative contribution of
      environmental and genetic factors to psychoactive medication use. METHOD: Sample
      consists of a population-based cohort comprising 437 pairs of female twins born
      between 1940 and 1966. Information is collected through individual interviews,
      and it includes employment status, educational level, partner status, menopause,
      presence of mental disorders and psychoactive medication use. Logistic regression
      models are applied. The relative contribution of genetic and environmental
      factors to interindividual variation is analyzed through the classical twin
      design. RESULTS: In the past month, 34.0% of the women interviewed had consumed
      psychoactive medication. Consumption increases with age, in women out of the
      labor market, menopausal, and reporting a history of mental disorders. When
      controlling for age, all variables lost significance, except the presence of
      mental health problems. Heritability estimates for psychoactive medication use
      was 52%. This estimate is similar (46%) for consumption in the two categories
      studied. CONCLUSIONS: There is a high prevalence of psychoactive medication use
      in this sample. This consumption is mainly associated with age and presence of
      mental disorders. About half of the interindividual variation in psychotropic
      medication use is attributable to genetic factors, while the rest of the variance
      would be due to environmental factors unique to each individual.

PMID- 23884616
TI  - To what extent are specific psychotherapies for borderline personality disorders
      efficacious? A systematic review of published randomised controlled trials.
AB  - INTRODUCTION: Over the past 20 years, several studies have established the
      efficacy of different forms of psychotherapy for borderline personality disorders
      (BPD). However, existing research has used a wide range of outcomes measures
      which makes it difficult to quantify data and to compare interventions. This
      review has been designed to analyse the evidence from randomized controlled
      trials (RCT) through a qualitative approach. METHODS: A systematic review of
      published RCT on specific psychotherapies for BPD has been undertaken to find
      relevant literature from online PsycINFO, ISI Web of Knowledge and Medline
      databases. An analysis of variability in primary outcomes, dropout patients and
      those who do not enter treatment has been conducted to assess if a wide range of
      variation could show any potential bias. RESULTS: There is a substantial
      variation between the studies in primary outcomes, such as suicide attempts (7.4-
      33.9%), and specially in dropout patients (6.7-47.4%) and those who do not enter
      treatment (17.6-63.6%). Globally, specific psychotherapy for BPD, at least in a
      40% of patients who demand treatment, would not be efficacious. CONCLUSIONS: The
      overall efficacy of specific therapies for BPD is promising. However, the
      variability of results raise questions about potential bias. Future studies
      should investigate new therapeutic approaches to allow the management of more
      severe and refractory patients.

PMID- 23884617
TI  - [Francisco Varela's neurophenomenology of time: temporality of consciousness
      explained?].
AB  - This article attempts to clarify Francisco Varela's proposal of a
      neurophenomenology of time consciousness in the light of distinctions based on
      the philosophical literature of phenomenology and recent advances of
      neurobiology. The analysis is carried out considering three aspects. In the first
      of them, we discuss the phenomenological aspect of consciousness, accessible in
      first-person, which describes time as a structure with three inseparable moments
      (past-present-future) and three levels of temporality, and not merely as the
      chronometric time or clock time. In the second one, we analyze the
      neurobiological aspect of consciousness that tends to "explain" the
      phenomenological time in terms of three possible levels of neuronal integration.
      Thus, we propose a correspondence between the levels of phenomenological time and
      neural integration processes. Finally, we try to analyze this "correspondence"
      and the issues that follow from this by considering that the notion of time in
      this correspondence is, in essence, the clock time and not the phenomenological
      time consciousness.

PMID- 23884618
TI  - Attenuation of dichlorvos-induced microglial activation and neuronal apoptosis by
      4-hydroxy TEMPO.
AB  - The neurotoxic consequences of acute high-level as well as chronic low-level
      organophosphates exposure are associated with a range of abnormalities in nerve
      functions. Previously, we have shown that after 24 h of dichlorvos exposure,
      microglia become activated and secrete pro-inflammatory molecules like nitric
      oxide, tumour necrosis factor-alpha and interleukin-1beta. Here, we extended our
      findings and focused on the neuronal damage caused by dichlorvos via microglial
      activation. For this, neurons and microglia were isolated separately from 1-day
      old Wistar rat pups. Microglia were treated with dichlorvos for 24 h and
      supernatant was collected (dichlorvos-induced conditioned medium, DCM). However,
      when 4-hydroxy TEMPO (4-HT) pretreatment was given, we observed significant
      attenuation of dichlorvos-induced microglial activation; we also collected the
      supernatant of this culture (4-HT + DCM, TDCM). Next, we checked the effects of
      DCM on neurons and found heavy loss in viability as evident from NF-H
      immunostaining and MTT results, whereas dichlorvos alone-treated neurons showed
      comparatively less damage. However, we observed significant increase in neuronal
      viability when cells were treated with TDCM. Semi-quantitative PCR and western
      blot results revealed significant increase in p53, Bax and cytochrome c levels
      along with caspase 3 activation after 24 h of DCM treatment. However, TDCM
      treated neurons showed significant decrease in the expression of these pro
      apoptotic molecules. Taken together, these findings suggest that 4-HT can
      significantly attenuate dichlorvos-induced microglial activation and prevent
      apoptotic neuronal cell death. 

PMID- 23884619
TI  - Pathways of neurotoxicity and innovative neuroprotective strategies. Preface.

PMID- 23884620
TI  - Thorascopic resection of an apical paraspinal schwannoma using the da Vinci
      surgical system.
AB  - BACKGROUND: Posterior mediastinal neurogenic tumors have traditionally been
      resected via an open posterolateral thoracotomy. Video-assisted thorascopic
      surgery has emerged as an alternative technique allowing for improved morbidity
      with decreased blood loss, less postoperative pain, and a shorter recovery
      period, among others. The da Vinci surgical system, as first described for
      urologic procedures, has recently been reported for lung lobectomy. This
      technique provides the advantages of instrumentation with 6 degrees of freedom,
      stable operating arms, and improved visualization with the three-dimensional high
      definition camera. METHODS: We describe the technique for thorascopic resection
      of an apical paraspinal schwannoma of the T1 nerve root with the da Vinci
      surgical system. This technique used a specialized intraoperative neuromonitoring
      probe for free-running electromyography (EMG) and triggered EMG. RESULTS: We
      demonstrate successful resection of a posterior paraspinal schwannoma with the da
      Vinci surgical system while preserving neurologic function. The patient displayed
      stable intraoperative monitoring of the T1 nerve root and full intrinsic hand
      strength postoperatively. CONCLUSION: The technique described in this article
      introduces robotic system accuracy and precludes the need for an open
      thoracotomy. In addition, this approach demonstrates the ability of the da Vinci
      surgical system to safely dissect tumors from their neural attachments and is
      applicable to other such lesions of similar size and location.

PMID- 23884621
TI  - Callous-unemotional traits and antisocial behavior among adolescents: the role of
      self-serving cognitions.
AB  - Self-serving cognitions and callous-unemotional traits play important roles in
      adolescent antisocial behavior. The objective of this study was to cross
      sectionally explore the mediating role of self-serving cognitions in the
      relationship between callous-unemotional traits and antisocial behavior. A sample
      of 972 high-school students completed self-report questionnaires assessing
      callous-unemotional traits, self-serving cognitive distortions and antisocial
      behavior. Two competing models exploring indirect effects accounting for the
      relationships between self-serving cognitive distortions, callous-unemotional
      traits and antisocial behaviors were tested. Both models revealed significant
      indirect effects, suggesting both pathways are possible. Gender was found to
      moderate these models. These findings suggest the importance of targeting self
      serving cognitions in therapeutic interventions and increase our understanding of
      the role of self-serving cognitions in antisocial behavior. 

PMID- 23884622
TI  - Influence of bag volume on reproducibility of inert gas rebreathing pulmonary
      blood flow measurements in patients with pulmonary diseases.
AB  - PURPOSE: Non-invasive inert gas rebreathing (IGR) has shown promising results in
      the determination of pulmonary blood flow. The volume of the rebreathing bag (V
      bag) is proposed by the system. However, elderly patients or those with severe
      pulmonary disease may be unable to rebreathe this volume entirely. We evaluated
      the effect of adapting V bag on the reproducibility of IGR. METHODS: A total of
      270 valid measurements were obtained from 45 patients with obstruction (group A),
      restriction (group B), and in healthy controls (group C). Two measurements for
      each of three different V bag of 1,200, 1,700, and 2,200 ml were conducted in the
      supine position. RESULTS: We found no statistically significant difference of the
      repeated measurements neither between the different V bag in groups A to C nor
      between the three groups for identical V bag. There was a weak yet significantly
      worse coefficient of variation between a V bag of 2,200 ml in group A compared
      with group C with 2,200 and 1,200 ml, respectively. Intraclass correlation
      coefficient and repeatability coefficient yielded significantly worse values in
      group A for a V bag of 2,200 ml compared with healthy controls and lower bag
      volumes. No difference could be found intraclass nor interclass in groups B and
      C. CONCLUSIONS: V bag can be altered between 1,200 and 2,200 ml in most
      situations without affecting the reproducibility. Attention has to be paid to
      extreme volumes in obstructive patients. Nevertheless, V bag should be chosen as
      large as possible and therefore has to be carefully adapted, particularly in
      patients with obstruction or restriction.

PMID- 23884623
TI  - Influence of charge density on bilayer bending rigidity in lipid vesicles: a
      combined dynamic light scattering and neutron spin-echo study.
AB  - We report a combined dynamic light scattering and neutron spin-echo study on
      vesicles composed of the uncharged stabilizing lipid 1,2-dimyristoyl-sn-glycero-3
      phosphatidylcholine (DMPC) and the cationic lipid 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP). Mechanical properties of a model membrane and
      thus the corresponding bilayer undulation dynamics can be specifically tuned by
      changing its composition through lipid headgroup or acyl chain properties. We
      compare the undulation dynamics in lipid vesicles composed of DMPC/DOTAP to
      vesicles composed of a mixture of the uncharged helper lipid DMPC with the also
      uncharged reference lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). We
      have performed dynamic light scattering on the lipid mixtures to investigate
      changes in lipid vesicle size and the corresponding center-of-mass diffusion. We
      study lipid translational diffusion in the membrane plane and local bilayer
      undulations using neutron spin-echo spectroscopy, on two distinct time scales,
      namely around 25 ns and around 150 ns. Finally, we calculate the respective
      bilayer bending rigidities kappa for both types of lipid vesicles. We find that
      on the local length scale inserting lipid headgroup charge into the membrane
      influences the bilayer undulation dynamics and bilayer bending rigidity kappa
      less than inserting lipid acyl chain unsaturation: We observe a bilayer softening
      with increasing inhomogenity of the lipid mixture, which could be caused by a
      hydrophobic mismatch between the acyl chains of the respective lipid components,
      causing a lateral phase segregation (domain formation) in the membrane plane. 

PMID- 23884624
TI  - Nanoscale protein dynamics: a new frontier for neutron spin echo spectroscopy.
AB  - Recent studies show that neutron spin echo spectroscopy (NSE) can reveal long
      range protein domain motions on nanometer lengthscales and on nanosecond to
      microsecond timescales. This unique capability of NSE provides new opportunities
      to understand protein dynamics and functions, such as how binding signals are
      propagated in a protein to distal sites. Here we review our applications of NSE
      to the study of nanoscale protein domain motions in a set of cell signaling
      proteins. We summarize the theoretical framework we have developed, which allows
      one to interpret the NSE data (Biophys. J. 99, 3473 (2010) and Proc. Natl. Acad.
      Sci. USA 102, 17646 (2005)). Our theoretical framework uses simple concepts from
      nonequilibrium statistical mechanics, and does not require elaborate molecular
      dynamics simulations, complex fits to rotational motion, or elastic network
      models. It is thus more robust than multiparameter techniques that require
      untestable assumptions. We also demonstrate our experimental scheme involving
      deuterium labeling of a protein domain or a subunit in a protein complex. We show
      that our selective deuteration scheme can highlight and resolve specific domain
      dynamics from the abundant global translational and rotational motions in a
      protein. Our approach thus clears significant hurdles to the application of NSE
      for the study of protein dynamics in solution. 

PMID- 23884625
TI  - Perspectives in biological physics: the nDDB project for a neutron Dynamics Data
      Bank for biological macromolecules.
AB  - Neutron spectroscopy provides experimental data on time-dependent trajectories,
      which can be directly compared to molecular dynamics simulations. Its importance
      in helping us to understand biological macromolecules at a molecular level is
      demonstrated by the results of a literature survey over the last two to three
      decades. Around 300 articles in refereed journals relate to neutron scattering
      studies of biological macromolecular dynamics, and the results of the survey are
      presented here. The scope of the publications ranges from the general physics of
      protein and solvent dynamics, to the biologically relevant dynamics-function
      relationships in live cells. As a result of the survey we are currently setting
      up a neutron Dynamics Data Bank (nDDB) with the aim to make the neutron data on
      biological systems widely available. This will benefit, in particular, the MD
      simulation community to validate and improve their force fields. The aim of the
      database is to expose and give easy access to a body of experimental data to the
      scientific community. The database will be populated with as much of the existing
      data as possible. In the future it will give value, as part of a bigger whole, to
      high throughput data, as well as more detailed studies. A range and volume of
      experimental data will be of interest in determining how quantitatively MD
      simulations can reproduce trends across a range of systems and to what extent
      such trends may depend on sample preparation and data reduction and analysis
      methods. In this context, we strongly encourage researchers in the field to
      deposit their data in the nDDB.

PMID- 23884626
TI  - Proteins in amorphous saccharide matrices: structural and dynamical insights on
      bioprotection.
AB  - Bioprotection by sugars, and in particular trehalose peculiarity, is a relevant
      topic due to the implications in several fields. The underlying mechanisms are
      not yet clearly elucidated, and remain the focus of current investigations. Here
      we revisit data obtained at our lab on binary sugar/water and ternary
      protein/sugar/water systems, in wide ranges of water content and temperature, in
      the light of the current literature. The data here discussed come from
      complementary techniques (Infrared Spectroscopy, Molecular Dynamics simulations,
      Small Angle X-ray Scattering and Calorimetry), which provided a consistent
      description of the bioprotection by sugars from the atomistic to the macroscopic
      level. We present a picture, which suggests that protein bioprotection can be
      explained in terms of a strong coupling of the biomolecule surface to the matrix
      via extended hydrogen-bond networks, whose properties are defined by all
      components of the systems, and are strongly dependent on water content.
      Furthermore, the data show how carbohydrates having similar hydrogen-bonding
      capabilities exhibit different efficiency in preserving biostructures. 

PMID- 23884627
TI  - pAO1 of Arthrobacter nicotinovorans and the spread of catabolic traits by
      horizontal gene transfer in gram-positive soil bacteria.
AB  - The 165-kb megaplasmid pAO1 of Arthrobacter nicotinovorans carries two large gene
      clusters, one involved in nicotine catabolism (nic-gene cluster) and one in
      carbohydrate utilization (ch-gene cluster). Here, we propose that both gene
      clusters were acquired by A. nicotinovorans by horizontal gene transfer mediated
      by pAO1. Protein-protein blast search showed that none of the published
      Arthrobacter genomes contains nic-genes, but Rhodococcus opacus carries on its
      chromosome a nic-gene cluster highly similar to that of pAO1. Analysis of the nic
      genes in the two species suggested a recombination event between their nic-gene
      clusters. Apparently, there was a gene exchange between pAO1, or a precursor
      plasmid, and a nic-gene cluster of an as yet unidentified Arthrobacter specie or
      other soil bacterium, possibly related to Rhodococcus, leading to the transfer by
      pAO1 of this catabolic trait to A. nicotinovorans. Analysis of the pAO1 ch-gene
      cluster revealed a virtually identical counterpart on the chromosome of
      Arthrobacter phenanthrenivorans. Moreover, the sequence analysis of the genes
      flanking the ch-gene cluster suggested that it was acquired by pAO1 by Xer
      related site directed recombination and transferred via the plasmid to A.
      nicotinovorans. The G+C content, the level of sequence identity, gene co
      linearity of nic- and ch-gene clusters as well as the signs of recombination
      events clearly supports the notion of pAO1 and its precursor plasmids as vehicles
      in HGT among Gram + soil bacteria.

PMID- 23884628
TI  - Extracellular syntaxin4 triggers the differentiation program in teratocarcinoma
      F9 cells that impacts cell adhesion properties.
AB  - The proteins in the syntaxin family are known to mediate fusion of cytoplasmic
      vesicles to the target membrane, yet subpopulations of certain syntaxins,
      including syntaxin4, translocate across the cell membrane in response to external
      stimuli. Here, we show that extracellularly presented syntaxin4 impacts cell
      behavior and differentiation in teratocarcinoma F9 cells. While undifferentiated
      F9 cells extruded a small subpopulation of extracellular syntaxin4 at the lateral
      cell membrane, the induction of differentiation with all-trans retinoic acid (RA)
      abolished this localized expression pattern. We found that the cells that were
      stimulated in a non-directional fashion by extracellular syntaxin4 displayed a
      flattened shape and retained a substrate-bound morphology even under a long-term,
      serum-starved cultivation. Such a cellular response was also elicited by a
      circular peptide composed of the potential functional core of syntaxin4 (AIEPQK;
      amino acid residues 103~108) (ST4n1). While the proliferation and metabolism were
      not affected in these cells, cell-cell interaction became weakened and the
      expression of vinculin, a regulator of both intercellular and cell-substrate
      adhesion molecules, was altered. We also found that the expressions of several
      differentiation markers were up-regulated in cells stimulated with extracellular
      syntaxin4 and that syntaxin3, another family member, was most prominent.
      Intriguingly, forced expression of syntaxin3 induced the spread morphology in F9
      cells, indicating that syntaxin3 partly mediates the function of extracellular
      syntaxin4. These results demonstrate the involvement of a non-directional
      stimulation of extracellular syntaxin4 in the functional and morphological
      differentiation of F9 cells.

PMID- 23884629
TI  - Quantitative analysis of phytosterols in edible oils using APCI liquid
      chromatography-tandem mass spectrometry.
AB  - Previous methods for the quantitative analysis of phytosterols have usually used
      GC-MS and require elaborate sample preparation including chemical derivatization.
      Other common methods such as HPLC with absorbance detection do not provide
      information regarding the identity of the analytes. To address the need for an
      assay that utilizes mass selectivity while avoiding derivatization, a
      quantitative method based on LC-tandem mass spectrometry (LC-MS-MS) was developed
      and validated for the measurement of six abundant dietary phytosterols and
      structurally related triterpene alcohols including brassicasterol, campesterol,
      cycloartenol, beta-sitosterol, stigmasterol, and lupeol in edible oils. Samples
      were saponified, extracted with hexane and then analyzed using reversed phase
      HPLC with positive ion atmospheric pressure chemical ionization tandem mass
      spectrometry and selected reaction monitoring. The utility of the LC-MS-MS method
      was demonstrated by analyzing 14 edible oils. All six compounds were present in
      at least some of the edible oils. The most abundant phytosterol in all samples
      was beta-sitosterol, which was highest in corn oil at 4.35 +/- 0.03 mg/g,
      followed by campesterol in canola oil at 1.84 +/- 0.01 mg/g. The new LC-MS-MS
      method for the quantitative analysis of phytosterols provides a combination of
      speed, selectivity and sensitivity that exceed those of previous assays. 

PMID- 23884630
TI  - Taurine supplementation of plant derived protein and n-3 fatty acids are critical
      for optimal growth and development of cobia, Rachycentron canadum.
AB  - We examined growth performance and the lipid content in juvenile cobia,
      Rachycentron canadum, fed a taurine supplemented (1.5 %), plant protein based
      diet with two fish oil replacements. The first fish oil replacement was a
      thraustochytrid meal (TM + SOY) plus soybean oil (~9 % CL) and the second was a
      canola oil supplemented with the essential fatty acids (EFA) docosahexaenoic acid
      (DHA) and arachidonic acid (ARA) (~8 % CL). The diet using the thraustochytrid
      meal plus soybean oil performed equivalently to the fish oil diet; both resulting
      in significantly higher growth rates, lower feed conversion ratios, and higher
      survival than the supplemented canola oil diet, even though all three diets were
      similar in overall energy and met known protein and lipid requirements for cobia.
      The poor performance of the canola oil diet was attributed to insufficient
      addition of EFA in the supplemented canola oil source. Increasing levels of EFA
      in the supplemented canola oil above 0.5 g EFA kg(-1) would likely improve
      results with cobia. When fish fed either of the fish oil replacement diets were
      switched to the fish oil control diet, fatty acid profiles of the fillets were
      observed to transition toward that of the fish oil diet and could be predicted
      based on a standard dilution model. Based on these findings, a formulated diet
      for cobia can be produced without fish products providing 100 % survivorship,
      specific growth rates greater than 2.45 and feed conversion ratios less than 1.5,
      as long as taurine is added and EFA levels are above 0.5 g EFA kg(-1). 

PMID- 23884632
TI  - The effect of cell line, phylogenetics and medium on baculovirus budded virus
      yield and quality.
AB  - The performance of bioprocesses involving baculoviruses largely depends on an
      efficient infection of cells by concentrated budded virus (BV) inoculums.
      Baculovirus expression vector systems have been established using Autographa
      californica nucleopolyhedrovirus (AcMNPV), a group I NPV that displays rapid
      virus kinetics, whereas bioprocesses using group II baculovirus-based
      biopesticides such as Helicoverpa armigera nucleopolyhedrovirus (HearNPV) have
      the limitation of low levels of BV, as these viruses often display poor BV
      production kinetics. In this study, the effect of key parameters involved in the
      quality of progeny virions, including cell line, virus phylogenetics and medium,
      on viral DNA replication, virus trafficking to the extracellular environment, and
      the yield of recombinant protein or polyhedra were investigated in synchronous
      infections of HearNPV and AcMNPV. HearNPV showed higher vDNA replication in its
      optimum medium, SF900III, when compared to AcMNPV, but both viruses had similar
      specific extracellular virion content. However, the ratio of AcMNPV extracellular
      virions to the total number of progeny virions produced was higher, and their
      quality was tenfold higher than that of HearNPV extracellular virions. The
      results of infection of two different cell lines, High Five and Sf9, with AcMNPV,
      along with HearNPV infection of HzAM1 cells in three different media, suggest
      that the host cells and the nutritional state of the medium as well as the
      phylogenetics of the virus affect the BV yields produced by different
      baculovirus/cell line/medium combinations. 

PMID- 23884631
TI  - Time window expansion for HDX analysis of an intrinsically disordered protein.
AB  - Application of typical HDX methods to examine intrinsically disordered proteins
      (IDP), proteins that are natively unstructured and highly dynamic at
      physiological pH, is limited because of the rapid exchange of unprotected amide
      hydrogens with solvent. The exchange rates of these fast exchanging amides are
      usually faster than the shortest time scale (10 s) employed in typical automated
      HDX-MS experiments. Considering the functional importance of IDPs and their
      association with many diseases, it is valuable to develop methods that allow the
      study of solution dynamics of these proteins as well as the ability to probe the
      interaction of IDPs with their wide range of binding partners. Here, we report
      the application of time window expansion to the millisecond range by altering the
      on-exchange pH of the HDX experiment to study a well-characterized IDP; the
      activation domain of the nuclear receptor coactivator, peroxisome proliferator
      activated receptor gamma coactivator-1 alpha (PGC-1alpha). This method enabled
      mapping the regions of PGC-1alpha that are stabilized upon binding the ligand
      binding domain (LBD) of the nuclear receptor peroxisome proliferator-activated
      receptor gamma (PPARgamma). We further demonstrate the method's applicability to
      other binding partners of the IDP PGC-1alpha and pave the way for characterizing
      many other biologically important ID proteins. 

PMID- 23884633
TI  - Genetic diversity in the G protein gene of group A human respiratory syncytial
      viruses circulating in Riyadh, Saudi Arabia.
AB  - Human respiratory syncytial virus (HRSV) is a frequent cause of hospitalization
      and mortality in children worldwide. The molecular epidemiology and circulation
      pattern of HRSV in Saudi Arabia is mostly uncharted. In the current study, the
      genetic variability and phylogenetic relationships of HRSV type A strains
      circulating in Riyadh Province were explored. Nasopharyngeal aspirates were
      collected from hospitalized children with acute respiratory symptoms during the
      winter-spring seasons of 2007/08 and 2008/09. Among 175 samples analyzed, 39
      (22.3 %) were positive for HRSV by one-step RT-PCR (59 % type A and 41 % type B).
      Propagation of positive samples in HEp-2 cells permitted the recovery of the
      first Saudi HRSV isolates. Genetic variability among Saudi HRSV-A strains was
      evaluated by sequence analysis of the complete attachment (G) protein gene. The
      nucleotide sequence was compared to representatives of the previously identified
      HRSV-A genotypes. Sequence and phylogenetic analysis showed that the strains
      examined in this study were very closely related at both the nucleotide and amino
      acid level, and all of them are clustered in the GA2 genotype (and mostly
      belonged to the NA-1 subtype). A total of 23 mutation sites, 14 of which resulted
      in an amino acid change, were recorded only in Saudi strains. This is the first
      report on genetic diversity of HRSV-A strains in Saudi Arabia. Further analysis
      of strains on a geographical and temporal basis is needed to fully understand
      HRSV-A circulation patterns in Saudi Arabia. 

PMID- 23884634
TI  - Natural antisense transcripts of UL123 packaged in human cytomegalovirus virions.
AB  - In this study, we demonstrated that antisense transcripts of human
      cytomegalovirus (HCMV) UL123, UL21.5 and cellular GAPDH genes were present in
      highly purified virions. These virion RNAs were delivered into the host cells
      upon infection, and de novo synthesized ones appeared in the infected cell at the
      immediate early stage. Although the sequence of UL123 antisense transcripts in
      virions is uncertain, we found that these transcripts in Towne-infected human
      fibroblasts had novel transcriptional start sites (TSSs) with various 5'-terminal
      deletions of open reading frame (ORF) 59. These findings not only provide new
      insight into the composition of HCMV virions but also reveal a possible viral
      strategy for initiating latent infection and switching between latent and
      productive infections. 

PMID- 23884635
TI  - Retrospective serosurveillance of bovine norovirus (GIII.2) and nebovirus in
      cattle from selected feedlots and a veal calf farm in 1999 to 2001 in the United
      States.
AB  - There is a dearth of information on the seroprevalence of bovine norovirus
      (BoNoV) and nebovirus in cattle of the US. In this retrospective study, serum IgG
      antibodies to two bovine enteric caliciviruses, GIII.2 BoNoV (Bo/CV186-OH/00/US)
      and genetically and antigenically distinct nebovirus (Bo/NB/80/US), were
      evaluated in feedlot and veal calves from different regions of the US during 1999
      2001. Three groups of 6- to 7-month-old feedlot calves from New Mexico (NM)
      (n=103), Arkansas (AR) (n=100) and Ohio (OH) (n=140) and a group of 7- to 10-day
      old Ohio veal calves (n=47) were studied. Serum samples were collected pre
      arrival or at arrival to the farms for the NM, AR and OH calves and 35 days after
      arrival for all groups for monitoring seroconversion rates during the period.
      Virus-like particles of Bo/CV186-OH/00/US and Bo/NB/80/US were expressed using
      the baculovirus expression system and were used in ELISA to measure antibodies. A
      high seroprevalence of 94-100 % and 78-100 % was observed for antibodies to
      GIII.2 BoNoV and nebovirus, respectively, in the feedlot calves tested. In the
      Ohio veal farm, an antibody seroprevalence of 94-100 % and 40-66 % was found for
      GIII.2 BoNoV and nebovirus, respectively. Increased seropositive rates of 38-85 %
      for GIII.2 BoNoV and 26-83 % for nebovirus were observed at 35 days after arrival
      and commingling on farms for all groups. Infection of calves with either GIII.2
      BoNoV or nebovirus, or both viruses, appeared to be common in the regions studied
      in the US during 1999-2001. These two viruses likely remain endemic because no
      commercial vaccines are available. 

PMID- 23884636
TI  - Evaluation of fluorescence in situ hybridization for the detection of bacteria in
      feline inflammatory liver disease.
AB  - The etiopathogenesis of feline inflammatory liver disease (ILD) is unclear.
      Therefore, we sought to determine the presence and distribution of bacteria
      within the livers of cats with ILD using eubacterial fluorescence in situ
      hybridization (FISH). Histopathology from 39 cats with ILD and 19 with
      histologically normal livers (C) were classified using World Small Animal
      Veterinary Association guidelines. Hepatic sections were examined by 16 and 23S
      ribosomal RNA FISH. Antibodies against cytokeratins and factor VIIIa were used to
      distinguish bile ducts and vascular structures. Histopathologic findings included
      non-specific reactive hepatitis (12), neutrophilic cholangitis (NC; 12),
      lymphocytic cholangitis (seven), cholestasis/obstruction (three), probable
      lymphoma (three) and acute hepatitis (two). Bacteria were observed in 21/39 ILD
      and 3/19 C (P = 0.0054). In 8/39 ILD and 2/19 C bacteria were restricted to the
      outer liver capsule (P = 0.29) and may represent contaminants. The prevalence of
      intrahepatic bacteria was higher (P = 0.008) in ILD (13/31) than C (1/17).
      Bacteria in ILD were more frequently (P <0.0001) localized to portal vessels,
      venous sinusoids and parenchyma (12/13) than bile duct (1/13). Bacterial
      colonization was highest in Escherichia coli-positive NC cats. Concurrent non
      hepatic disease, predominantly pancreatic and intestinal (8/10 cats biopsied),
      was present in all 13 cats with intrahepatic bacteria. Bacterial culture was
      positive (predominantly E coli and Enterococcus species) in 11/23 (48%) samples,
      and concurred with FISH in 15/23 cases. The presence of intrahepatic bacteria in
      13/31 (41%) cats with ILD suggests a role in etiopathogenesis. The distribution
      of bacteria within the liver supports the possibility of colonization via either
      enteric translocation or hematogenous seeding. 

PMID- 23884637
TI  - Cloprostenol treatment of feline open-cervix pyometra.
AB  - Treatment with cloprostenol, a prostaglandin synthetic analogue, was evaluated in
      five queens with open-cervix pyometra. Cloprostenol was administered (5 MUg/kg
      body weight SC) on 3 consecutive days and amoxicillin (20 mg/kg body weight IM)
      on 7 consecutive days. Transient post-injection reactions caused by cloprostenol
      administration included diarrhea, vomiting and vocalizations. Reactions began as
      quickly as 10 mins after cloprostenol administration and lasted as long as 30
      mins. All queens improved clinically after cloprostenol treatment and remained
      healthy until the end of the study, 1 year after treatment. All queens resumed
      normal estrous cycles without further treatment and two (40%) delivered a normal
      litter. In conclusion, use of cloprostenol is an acceptable treatment for open
      cervix pyometra in queens. 

PMID- 23884638
TI  - Fatigue management in patients with IBD: a randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of solution-focused therapy (SFT) on
      fatigue and quality of life (QoL) in patients with fatigued inflammatory bowel
      disease (IBD). DESIGN: Randomised controlled trial in two Dutch hospitals.
      Patients with IBD with quiescent IBD and with a Checklist Individual Strength-
      Fatigue (CIS--fatigue) score of >= 35 were enrolled. Patients were 1:1 randomised
      to receive SFT or care as usual (CAU) for 3 months. Patients were followed for a
      further 6 months after the SFT. Primary endpoint was defined as changes in
      fatigue and QoL during follow-up. Secondary endpoints included change in anxiety
      and depression, medication use, side effects to medication, disease activity,
      laboratory parameters (C-reactive protein, leucocytes and haemoglobin) and sleep
      quality. RESULTS: Ninety-eight patients were included, of whom 63% were women,
      mean age was 40.1 years. After the SFT course, 17 (39%) patients in the SFT group
      had a CIS-fatigue score below 35 compared with eight (18%) of patients in the CAU
      group (p=0.03). The SFT group also showed a greater reduction in fatigue across
      the first 6 months compared with the CAU group (CIS-fatigue: p=<0.001 and CIS
      total: p=0.001). SFT was associated with a significant higher mean IBD
      questionnaire change at 3 months (p=0.020). At 9 months, no significant
      differences between the two groups were observed. CONCLUSIONS: SFT has a
      significant beneficial effect on the severity of fatigue and QoL in patients with
      quiescent IBD. However, this effect diminished during follow-up.

PMID- 23884639
TI  - Gene signatures distinguish stage-specific prostate cancer stem cells isolated
      from transgenic adenocarcinoma of the mouse prostate lesions and predict the
      malignancy of human tumors.
AB  - The relevant social and economic impact of prostate adenocarcinoma, one of the
      leading causes of death in men, urges critical improvements in knowledge of the
      pathogenesis and cure of this disease. These can also be achieved by implementing
      in vitro and in vivo preclinical models by taking advantage of prostate cancer
      stem cells (PCSCs). The best-characterized mouse model of prostate cancer is the
      transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice develop
      a progressive lesion called prostatic intraepithelial neoplasia that evolves into
      adenocarcinoma (AD) between 24 and 30 weeks of age. ADs often metastasize to
      lymph nodes, lung, bones, and kidneys. Eventually, approximately 5% of the mice
      develop an androgen-independent neuroendocrine adenocarcinoma. Here we report the
      establishment of long-term self-renewing PCSC lines from the different stages of
      TRAMP progression by application of the neurosphere assay. Stage-specific
      prostate cell lines were endowed with the critical features expected from
      malignant bona fide cancer stem cells, namely, self-renewal, multipotency, and
      tumorigenicity. Notably, transcriptome analysis of stage-specific PCSCs resulted
      in the generation of well-defined, meaningful gene signatures, which identify
      distinct stages of human tumor progression. As such, TRAMP-derived PCSCs
      represent a novel and valuable preclinical model for elucidating the pathogenetic
      mechanisms leading to prostate adenocarcinoma and for the identification of
      molecular mediators to be pursued as therapeutic targets.

PMID- 23884640
TI  - Sustained release of bone morphogenetic protein 2 via coacervate improves the
      osteogenic potential of muscle-derived stem cells.
AB  - Muscle-derived stem cells (MDSCs) isolated from mouse skeletal muscle by a
      modified preplate technique exhibit long-term proliferation, high self-renewal,
      and multipotent differentiation capabilities in vitro. MDSCs retrovirally
      transduced to express bone morphogenetic proteins (BMPs) can differentiate into
      osteocytes and chondrocytes and enhance bone and articular cartilage repair in
      vivo, a feature that is not observed with nontransduced MDSCs. These results
      emphasize that MDSCs require prolonged exposure to BMPs to undergo osteogenic and
      chondrogenic differentiation. A sustained BMP protein delivery approach provides
      a viable and potentially more clinically translatable alternative to genetic
      manipulation of the cells. A unique growth factor delivery platform comprised of
      native heparin and a synthetic polycation, poly(ethylene argininylaspartate
      diglyceride) (PEAD), was used to bind, protect, and sustain the release of bone
      morphogenetic protein-2 (BMP2) in a temporally and spatially controlled manner.
      Prolonged exposure to BMP2 released by the PEAD:heparin delivery system promoted
      the differentiation of MDSCs to an osteogenic lineage in vitro and induced the
      formation of viable bone at an ectopic site in vivo. This new strategy represents
      an alternative approach for bone repair mediated by MDSCs while bypassing the
      need for gene therapy.

PMID- 23884641
TI  - Trichostatin A enhances differentiation of human induced pluripotent stem cells
      to cardiogenic cells for cardiac tissue engineering.
AB  - Human induced pluripotent stem (iPS) cells are a promising source of autologous
      cardiomyocytes to repair and regenerate myocardium for treatment of heart
      disease. In this study, we have identified a novel strategy to enhance cardiac
      differentiation of human iPS cells by treating embryoid bodies (EBs) with a
      histone deacetylase inhibitor, trichostatin A (TSA), together with activin A and
      bone morphogenetic protein 4 (BMP4). Over a narrow window of concentrations, TSA
      (1 ng/ml) directed the differentiation of human iPS cells into a cardiomyocyte
      lineage. TSA also exerted an additive effect with activin A (100 ng/ml) and BMP4
      (20 ng/ml). The resulting cardiomyocytes expressed several cardiac-specific
      transcription factors and contractile proteins at both gene and protein levels.
      Functionally, the contractile EBs displayed calcium cycling and were responsive
      to the chronotropic agents isoprenaline (0.1 MUM) and carbachol (1 MUM).
      Implanting microdissected beating areas of iPS cells into tissue engineering
      chambers in immunocompromised rats produced engineered constructs that supported
      their survival, and they maintained spontaneous contraction. Human cardiomyocytes
      were identified as compact patches of muscle tissue incorporated within a host
      fibrocellular stroma and were vascularized by host neovessels. In conclusion,
      human iPS cell-derived cardiomyocytes can be used to engineer functional cardiac
      muscle tissue for studying the pathophysiology of cardiac disease, for drug
      discovery test beds, and potentially for generation of cardiac grafts to
      surgically replace damaged myocardium.

PMID- 23884642
TI  - Cord blood transplantation for cure of HIV infections.
AB  - HIV infection has not been cured by antiretroviral drugs or gene therapy, but it
      has been cured by a hematopoietic cell transplantation (HCT) that was performed
      for a patient with acute myeloid leukemia and HIV infection using peripheral
      blood stem cells from an adult donor homozygous for CCR5-Delta32 (CCR5
      Delta32/Delta32). HIV has remained undetectable more than 6 years after
      discontinuation of antiretroviral therapy. However, this approach cannot be
      readily generalized because of the low prevalence of the CCR5-Delta32 allele and
      the need for a very close human leukocyte antigen (HLA) match between adult
      donors and recipients, as when bone marrow or peripheral blood stem cell
      transplants are performed. In contrast, cord blood (CB) transplants require less
      stringent HLA matching. CB units are being screened to develop an inventory of
      cryopreserved homozygous CCR5-Delta32 units available for HCT. One hundred eighty
      homozygous CCR5-Delta32 units have been identified, and 300 units are projected
      to provide for white pediatric patients a 73.6% probability of finding an
      adequately HLA-matched unit with a minimal cell dose of >=2.5 * 10(7) total
      nucleated cells (TNC) per kilogram and for white adults a 27.9% probability. With
      a minimal cell dose requirement of >=1 * 10(7) TNC per kilogram, the
      corresponding projected probabilities are 85.6% and 82.1%. CB transplantation
      does not require as stringent an HLA match between donor and recipient as bone
      marrow or peripheral blood HCTs, and HCT using cord bloods from donors homozygous
      for CCR5-Delta32 is, at the present time, the only feasible means of treatment of
      reasonable numbers of patients who are infected with HIV. 

PMID- 23884643
TI  - Restraint stress impairs oocyte developmental potential in mice: role of CRH
      induced apoptosis of ovarian cells.
AB  - This study examined the role of CRH-induced ovarian cell apoptosis in the
      restraint stress (RS)-induced impairment of oocyte competence. Oocyte percentages
      of apoptotic cumulus cells (CCs) did not differ between stressed and control mice
      before in vitro maturation (IVM) but became significantly higher in stressed mice
      after IVM without serum, growth factor, and hormone. The level of Bcl2 mRNA
      decreased significantly in mural granulosa cells (MGCs) and ovarian homogenates
      after RS. Whereas ovarian estradiol, testosterone, and IGF1 decreased, cortisol
      and progesterone increased significantly following RS. RS increased the level of
      CRH in serum, ovary, and oocyte while enhancing the expression of CRHR1 in CCs,
      MGCs, and thecal cells. RS down-regulated ovarian expression of glucocorticoid
      receptor and brain-derived neurotrophic factor. Furthermore, CRH supplementation
      to IVM medium impaired oocyte developmental potential while increasing apoptotic
      CCs, an effect that was completely overcome by addition of the CRHR1 antagonist
      antalarmin. Results suggest that RS impaired oocyte competence by increasing CRH
      but not glucocorticoids. Increased CRH initiated a latent apoptotic program in
      CCs and oocytes during their intraovarian development, which was executed later
      during IVM to impair oocyte competence. Thus, elevated CRH interacted with
      increased CRHR1 on thecal cells and MGCs, reducing the production of
      testosterone, estrogen, and IGF1 while increasing the level of progesterone. The
      imbalance between estrogen and progesterone and the decreased availability of
      growth factors triggered apoptosis of MGCs and facilitated CC expression of
      CRHR1, which interacted with the oocyte-derived CRH later during IVM to induce CC
      apoptosis and reduce oocyte competence. 

PMID- 23884644
TI  - Survival of drowning sperm: do spermatozoa from external fertilizers adapt to
      differing osmotic environments through the use of aquaporins?

PMID- 23884645
TI  - Stability of genomic imprinting and gestational-age dynamic methylation in
      complicated pregnancies conceived following assisted reproductive technologies.
AB  - For the past three decades, assisted reproductive technologies (ART) have
      revolutionized infertility treatments. The use of ART is thought to be safe.
      However, early investigations suggested that children born as a result of ART had
      higher risk of diseases with epigenetic etiologies, including imprinting
      disorders caused by a lack of maternal methylation at imprinting control
      elements. In addition, large epidemiology studies have highlighted an increased
      risk of obstetric complications, including severe intrauterine growth restriction
      (IUGR) in babies conceived using ART. It is plausible that the increased
      frequency of IUGR may be due to abnormal imprinting because these transcripts are
      key for normal fetal growth and development. To address this, we have collected a
      large cohort of placenta and cord blood samples from ART conceptions and compared
      the imprinting status with appropriate non-ART population. Using a custom DNA
      methylation array that simultaneously quantifies 25 imprinted differentially
      methylated regions, we observed similar epigenetic profiles between groups. A
      multiplex Sequenom iPLEX allelic expression assay revealed monoallelic expression
      for 11 imprinted transcripts in our placenta cohort. We also observe appropriate
      gestational age-dependent methylation dynamics at retrotransposable elements and
      promoters associated with growth genes in ART placental biopsies. This study
      confirms that children conceived by ART do not show variability in imprinted
      regulation and that loss-of-imprinting is not commonly associated with
      nonsyndromic IUGR or prematurity. 

PMID- 23884646
TI  - Production of fertile offspring from oocytes grown in vitro by nuclear transfer
      in cattle.
AB  - Because of recent advancements in reproductive technology, oocytes have attained
      an increasingly enriched value as a unique cell population in the production of
      offspring. The growing oocytes in the ovary are an immediate potential source
      that serve this need; however, complete oocyte growth before use is crucial. Our
      research objective was to create in vitro-grown (IVG) oocytes that would have the
      ability to perform specialized activities, including nuclear reprogramming, as an
      alternative to in vivo-grown oocytes. Bovine oocyte-granulosa cell complexes with
      a mean oocyte diameter of approximately 100 MUm were cultured on Millicell
      membrane inserts, with culture medium supplemented with 4% polyvinylpyrrolidone
      (molecular weight, 360,000), 20 ng/ml androstenedione, 2 mM hypoxanthine, and 5
      ng/ml bone morphogenetic protein 7. Oocyte viability after the 14-day culture
      period was 95%, and there was a 71% increase in oocyte volume. Upon induction of
      oocyte maturation, 61% of the IVG oocytes extruded a polar body. Eighty-four
      percent of the reconstructed IVG oocytes that used cumulus cells as donor cells
      underwent cleavage, and half of them became blastocysts. DNA methylation analyses
      of the satellite I and II regions of the blastocysts revealed a similar highly
      methylated status in the cloned embryos derived from in vivo-grown and IVG
      oocytes. Finally, one of the nine embryos reconstructed from the IVG oocytes
      developed into a living calf following embryo transfer. Fertility of the
      offspring was confirmed. In conclusion, the potential of a proportion of the IVG
      oocytes was comparable to that of in vivo-grown oocytes.

PMID- 23884647
TI  - Clinical and prothrombotic profile of hepatic vein outflow tract obstruction.
AB  - OBJECTIVE: To study the clinical as well as prothrombotic profile and outcome of
      hepatic venous outflow tract obstruction in children. METHODS: This is a
      prospective study of a cohort of hepatic venous outflow tract obstruction (HVOTO)
      pediatric cases. All children and adolescents presenting with acute or chronic
      liver disease were screened for HVOTO with ultrasound and Doppler imaging and
      confirmed by multidetector computerised tomography (MDCT) with contrast
      enhancement. RESULTS: Of the 162 cases of chronic liver disease, 13 (7.4 %) were
      diagnosed to have HVOTO. Ascites and edema over the feet were the most prominent
      features. Anabolic steroids and herbal drugs were being taken by one case each.
      Six cases were diagnosed on Doppler and for rest 7 cases conclusive diagnosis was
      made on multidetector computerised tomography. Five out of 13 cases were
      heterogenous (CT) for mutation of the gene encoding methylene tetrahydrofolate
      reductase (MTHFR) and one case of these was also heterogenous for Factor Leiden
      V. One case was known celiac and developed HVOTO and was also found to be having
      hepatocellular carcinoma. Other causes were drug induced, pressure on inferior
      vena cava (IVC) and inferior vena cava (IVC) web. Thus the authors could find a
      prothrombotic cause for 10 out of 13 (76.9 %) cases. Three cases did not need any
      intervention. In one patient with infective thrombus of the IVC intervention was
      not planned. Six underwent angioplasty and 3 underwent transjugular intrahepatic
      portosystemic shunt. All were asymptomatic with improving growth parameters at
      follow up. CONCLUSIONS: Ascites, pedal edema, prominent abdominal veins and
      hepatomegaly should raise the suspicion of HVOTO in childhood liver disease.
      Majority of the cases would be harbouring a prothrombotic cause. MTHFR mutation
      was the commonest cause of HVOTO in the present study. Angioplasty and/or
      transjugular intrahepatic portosystemic shunt (TIPSS) can successfully treat
      HVOTO.

PMID- 23884648
TI  - Clinical characteristics of paraquat poisoning in 22 Chinese children.
AB  - OBJECTIVE: To retrospectively analyze the clinical characteristics and experience
      of Chinese children with paraquat poisoning. METHODS: Twenty-two children with
      paraquat poisoning who presented to the hospital from October 2007 through
      September 2012 were enrolled into this study. The clinical indices of these cases
      were collected and analyzed. RESULTS: All the children were poisoned due to oral
      ingestion of paraquat. Different degrees of damage were found in multiple systems
      in their bodies. All of them were administered pulse therapy using
      methylprednisolone (20 mg/kg/d * 3d) and Gamma globulin (total 2 g/kg divided
      into 3 d to 5 d) in the early stage. Prednisone was then given orally for 4 wk to
      8 wk. The total mortality rate of the patients was 63.6 % (14 of 22 patients
      died). Statistical differences (P < 0.05) were found between the surviving and
      dead patients, with regard to age, plasma paraquat levels, the highest levels of
      alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase,
      total bilirubin, direct bilirubin, indirect bilirubin, blood urea nitrogen,
      creatinine and pH value, the lowest levels of PaO2, PaCO2 and SaO2. Plasma
      paraquat level was positively related to pH value, but was negatively related to
      PaO2, PaCO2 and SaO2 levels. None of the patients died from hepatic and renal
      complications. Pulmonary fibrosis was the most severe complication and the
      primary cause of death. CONCLUSIONS: Paraquat poisoning is difficult to cure. In
      this study, pulmonary fibrosis was the primary cause of death. Treatment by
      administering large doses of glucocorticoids and Gamma globulin proved to be
      effective in the early stage. However, the treatment may not reverse the
      development of pulmonary fibrosis. The long-term prognosis of paraquat poisoning
      was not optimistic. The plasma paraquat level could be a significant factor in
      predicting the prognosis.

PMID- 23884649
TI  - Reducing maternal weight improves offspring metabolism and alters (or modulates)
      methylation.

PMID- 23884650
TI  - SOX2-LIN28/let-7 pathway regulates proliferation and neurogenesis in neural
      precursors.
AB  - The transcription factor SRY (sex-determining region)-box 2 (SOX2) is an
      important functional marker of neural precursor cells (NPCs) and plays a critical
      role in self-renewal and neuronal differentiation; however, the molecular
      mechanisms underlying its functions are poorly understood. Using human embryonic
      stem cell-derived NPCs to model neurogenesis, we found that SOX2 is required to
      maintain optimal levels of LIN28, a well-characterized suppressor of let-7
      microRNA biogenesis. Exogenous LIN28 expression rescued the NPC proliferation
      deficit, as well as the early but not the late stages of the neurogenic deficit
      associated with the loss of SOX2. We found that SOX2 binds to a proximal site in
      the LIN28 promoter region and regulates LIN28 promoter acetylation, likely
      through interactions with the histone acetyltransferase complex. Misexpression of
      let-7 microRNAs in NPCs reduced proliferation and inhibited neuronal
      differentiation, phenocopying the loss of SOX2. In particular, we identified let
      7i as a novel and potent inhibitor of neuronal differentiation that targets MASH1
      and NGN1, two well-characterized proneural genes. In conclusion, we discovered
      the SOX2-LIN28/let-7 pathway as a unique molecular mechanism governing NPC
      proliferation and neurogenic potential. 

PMID- 23884651
TI  - Clades reach highest morphological disparity early in their evolution.
AB  - There are few putative macroevolutionary trends or rules that withstand scrutiny.
      Here, we test and verify the purported tendency for animal clades to reach their
      maximum morphological variety relatively early in their evolutionary histories
      (early high disparity). We present a meta-analysis of 98 metazoan clades
      radiating throughout the Phanerozoic. The disparity profiles of groups through
      time are summarized in terms of their center of gravity (CG), with values above
      and below 0.50 indicating top- and bottom-heaviness, respectively. Clades that
      terminate at one of the "big five" mass extinction events tend to have truncated
      trajectories, with a significantly top-heavy CG distribution overall. The
      remaining 63 clades show the opposite tendency, with a significantly bottom-heavy
      mean CG (relatively early high disparity). Resampling tests are used to identify
      groups with a CG significantly above or below 0.50; clades not terminating at a
      mass extinction are three times more likely to be significantly bottom-heavy than
      top-heavy. Overall, there is no clear temporal trend in disparity profile shapes
      from the Cambrian to the Recent, and early high disparity is the predominant
      pattern throughout the Phanerozoic. Our results do not allow us to distinguish
      between ecological and developmental explanations for this phenomenon. To the
      extent that ecology has a role, however, the paucity of bottom-heavy clades
      radiating in the immediate wake of mass extinctions suggests that early high
      disparity more probably results from the evolution of key apomorphies at the base
      of clades rather than from physical drivers or catastrophic ecospace clearing. 

PMID- 23884652
TI  - Ken Wilson: a scientific appreciation.

PMID- 23884653
TI  - Teleost skin, an ancient mucosal surface that elicits gut-like immune responses.
AB  - Skin homeostasis is critical to preserve animal integrity. Although the skin of
      most vertebrates is known to contain a skin-associated lymphoid tissue (SALT),
      very little is known about skin B-cell responses as well as their evolutionary
      origins. Teleost fish represent the most ancient bony vertebrates containing a
      SALT. Due to its lack of keratinization, teleost skin possesses living epithelial
      cells in direct contact with the water medium. Interestingly, teleost SALT
      structurally resembles that of the gut-associated lymphoid tissue, and it
      possesses a diverse microbiota. Thus, we hypothesized that, because teleost SALT
      and gut-associated lymphoid tissue have probably been subjected to similar
      evolutionary selective forces, their B-cell responses would be analogous.
      Confirming this hypothesis, we show that IgT, a teleost immunoglobulin
      specialized in gut immunity, plays the prevailing role in skin mucosal immunity.
      We found that IgT(+) B cells represent the major B-cell subset in the skin
      epidermis and that IgT is mainly present in polymeric form in the skin mucus.
      Critically, we found that the majority of the skin microbiota are coated with
      IgT. Moreover, IgT responses against a skin parasite were mainly limited to the
      skin whereas IgM responses were almost exclusively detected in the serum.
      Strikingly, we found that the teleost skin mucosa showed key features of
      mammalian mucosal surfaces exhibiting a mucosa-associated lymphoid tissue. Thus,
      from an evolutionary viewpoint, our findings suggest that, regardless of their
      phylogenetic origin and tissue localization, the chief immunoglobulins of all
      mucosa-associated lymphoid tissue operate under the guidance of primordially
      conserved principles. 

PMID- 23884654
TI  - Variations in atmospheric CO2 growth rates coupled with tropical temperature.
AB  - Previous studies have highlighted the occurrence and intensity of El Nino
      Southern Oscillation as important drivers of the interannual variability of the
      atmospheric CO2 growth rate, but the underlying biogeophysical mechanisms
      governing such connections remain unclear. Here we show a strong and persistent
      coupling (r(2) ~ 0.50) between interannual variations of the CO2 growth rate and
      tropical land-surface air temperature during 1959 to 2011, with a 1  degrees C
      tropical temperature anomaly leading to a 3.5 +/- 0.6 Petagrams of carbon per
      year (PgC/y) CO2 growth-rate anomaly on average. Analysis of simulation results
      from Dynamic Global Vegetation Models suggests that this temperature-CO2 coupling
      is contributed mainly by the additive responses of heterotrophic respiration (Rh)
      and net primary production (NPP) to temperature variations in tropical
      ecosystems. However, we find a weaker and less consistent (r(2) ~ 0.25)
      interannual coupling between CO2 growth rate and tropical land precipitation than
      diagnosed from the Dynamic Global Vegetation Models, likely resulting from the
      subtractive responses of tropical Rh and NPP to precipitation anomalies that
      partly offset each other in the net ecosystem exchange (i.e., net ecosystem
      exchange ~ Rh - NPP). Variations in other climate variables (e.g., large-scale
      cloudiness) and natural disturbances (e.g., volcanic eruptions) may induce
      transient reductions in the temperature-CO2 coupling, but the relationship is
      robust during the past 50 y and shows full recovery within a few years after any
      such major variability event. Therefore, it provides an important diagnostic tool
      for improved understanding of the contemporary and future global carbon cycle. 

PMID- 23884655
TI  - Word learning is mediated by the left arcuate fasciculus.
AB  - Human language requires constant learning of new words, leading to the
      acquisition of an average vocabulary of more than 30,000 words in adult life. The
      ability to learn new words is highly variable and may rely on the integration
      between auditory and motor information. Here, we combined diffusion imaging
      tractography and functional MRI to study whether the strength of anatomical and
      functional connectivity between auditory and motor language networks is
      associated with word learning ability. Our results showed that performance in
      word learning correlates with microstructural properties and strength of
      functional connectivity of the direct connections between Broca's and Wernicke's
      territories in the left hemisphere. This study suggests that our ability to learn
      new words relies on an efficient and fast communication between temporal and
      frontal areas. The absence of these connections in other animals may explain the
      unique ability of learning words in humans. 

PMID- 23884656
TI  - Rates and patterns of great ape retrotransposition.
AB  - We analyzed 83 fully sequenced great ape genomes for mobile element insertions,
      predicting a total of 49,452 fixed and polymorphic Alu and long interspersed
      element 1 (L1) insertions not present in the human reference assembly and
      assigning each retrotransposition event to a different time point during great
      ape evolution. We used these homoplasy-free markers to construct a mobile element
      insertions-based phylogeny of humans and great apes and demonstrate their
      differential power to discern ape subspecies and populations. Within this
      context, we find a good correlation between L1 diversity and single-nucleotide
      polymorphism heterozygosity (r(2) = 0.65) in contrast to Alu repeats, which show
      little correlation (r(2) = 0.07). We estimate that the "rate" of Alu
      retrotransposition has differed by a factor of 15-fold in these lineages. Humans,
      chimpanzees, and bonobos show the highest rates of Alu accumulation--the latter
      two since divergence 1.5 Mya. The L1 insertion rate, in contrast, has remained
      relatively constant, with rates differing by less than a factor of three. We
      conclude that Alu retrotransposition has been the most variable form of genetic
      variation during recent human-great ape evolution, with increases and decreases
      occurring over very short periods of evolutionary time.

PMID- 23884657
TI  - The Cancer Imaging Archive (TCIA): maintaining and operating a public information
      repository.
AB  - The National Institutes of Health have placed significant emphasis on sharing of
      research data to support secondary research. Investigators have been encouraged
      to publish their clinical and imaging data as part of fulfilling their grant
      obligations. Realizing it was not sufficient to merely ask investigators to
      publish their collection of imaging and clinical data, the National Cancer
      Institute (NCI) created the open source National Biomedical Image Archive
      software package as a mechanism for centralized hosting of cancer related
      imaging. NCI has contracted with Washington University in Saint Louis to create
      The Cancer Imaging Archive (TCIA)-an open-source, open-access information
      resource to support research, development, and educational initiatives utilizing
      advanced medical imaging of cancer. In its first year of operation, TCIA
      accumulated 23 collections (3.3 million images). Operating and maintaining a high
      availability image archive is a complex challenge involving varied archive
      specific resources and driven by the needs of both image submitters and image
      consumers. Quality archives of any type (traditional library, PubMed, refereed
      journals) require management and customer service. This paper describes the
      management tasks and user support model for TCIA. 

PMID- 23884658
TI  - Effect of irradiation on the expression of DNA repair genes studied in human
      fibroblasts by real-time qPCR using three methods of reference gene validation.
AB  - The aim of this study was to determine the effects of ionizing radiation on gene
      expression by using for a first time a qPCR platform specifically established for
      the detection of 94 DNA repair genes but also to test the robustness of these
      results by using three analytical methods (global pattern recognition,
      DeltaDeltaCq/Normfinder and DeltaDeltaCq/Genorm). Study was focused on these
      genes because DNA repair is known primarily to determine the radiation response.
      Six strains of normal human fibroblasts were exposed to 2 Gy, and changes in gene
      expression were analyzed 24 h thereafter. A significant change in gene expression
      was found for only few genes, but the genes detected were mostly different for
      the three analytical methods used. For GPR, a significant change was found for
      four genes, in contrast to the eight or nine genes when applying
      DeltaDeltaCq/Genorm or DeltaDeltaCq/Normfinder, respectively. When using all
      three methods, a significant change in expression was only seen for GADD45A and
      PCNA. These data demonstrate that (1) the genes identified to show an altered
      expression upon irradiation strongly depend on the analytical method applied, and
      that (2) overall GADD45A and PCNA appear to play a central role in this response,
      while no significant change is induced for any of the other DNA repair genes
      tested. 

PMID- 23884659
TI  - Pharmacokinetics and bioequivalence evaluation of leflunomide tablets in Korean
      healthy volunteers.
AB  - Leflunomide is a disease-modifying antirheumatic drug. The purpose of this study
      was to evaluate the bioequivalence of a test drug (CJ leflunomide) and a
      commercially available reference drug (Arava(r)) at 2 doses (10 and 20 mg) in
      healthy Korean volunteers. This was a single-dose (28 individuals enrolled at
      each dose group), randomized, open-label, 2-way crossover study. The 2 treatment
      periods were separated by a 56-day wash-out interval. Blood sampling was
      conducted until 672 h after drug administration. Plasma teriflunomide (active
      metabolite of leflunomide) concentrations were determined, and pharmacokinetic
      parameters were calculated. Bioequivalence was evaluated using an ANOVA model,
      based on the AUCt and the Cmax after administration of leflunomide tablets.
      Bioequivalence was defined as the 90% confidence intervals (CIs) of the geometric
      mean ratios (GMRs) of AUCt and Cmax for the test and reference drugs being within
      the range of 0.80-1.25. The GMRs (90% CI) for AUCt and Cmax were 0.9506 (0.9091
      0.9941) and 0.9861 (0.9360-1.0389), respectively, in the 10 mg study, and 0.9524
      (0.9101-0.9968) and 0.9740 (0.9314-1.0186), respectively, in the 20 mg study. The
      90% CIs of AUCt and Cmax at each dose were within the accepted range for
      bioequivalence. Based on the results, the test drug (CJ leflunomide) was
      bioequivalent to the commercially available reference drug (Arava(r)) at both
      doses.

PMID- 23884660
TI  - Development and validation of a high-performance liquid chromatography coupled
      with ultraviolet detection method for the determination of isocorydine in rat
      plasma and its application in pharmacokinetics.
AB  - A new HPLC-UV method has been developed, validated and applied for the
      determination of isocorydine (CAS 475-67-2) in rat plasma after oral or
      intravenous (i. v.) administration. Caffeine was used as the internal standard
      (IS). The analyte and IS were extracted from rat plasma by liquid-liquid
      extraction (LLE) with methyl tert-butyl ether and they were separated on an
      XTerra C18 column (250*4.6 mm, 5 um, pH 1-12) with UV detection at 264 nm. The
      mobile phase consisted of methanol and 0.02 mol/L potassium dihydrogen phosphate
      phosphoric acid buffer solution (pH 3.2) (30:70, v/v) at a flow rate of 1 mL/min
      for 8.5 min. The retention times of isocorydine and caffeine were approximately
      6.5 and 5.1 min, respectively. The good linearity of the calibration curves was
      observed over the concentration range of 0.05-8 ug/mL (n=8, r 2>=0.9995). The
      lower limit of quantification (LLOQ) was 0.05 ug/mL [signal to noise ratio
      (S/N)>=10], and the limit of detection (LOD) was demonstrated as 0.01 ug/mL
      (S/N>=3). The mean extraction recovery ranged from 83.7% to 89.5% at 3 quality
      control (QC) concentrations. Intra-day and inter-day precision (relative standard
      deviation, RSD%) were within 4.7% and accuracy (relative error, RE%) ranged from 
      1.2% to 4.5%. The developed method was successfully applied to determination of
      the pharmacokinetic properties of isocorydine in rats after oral administration
      at a dose of 20 mg/kg and i. v. injection at 5 mg/kg.

PMID- 23884661
TI  - Efficacy and safety of a once-daily extended-release formulation of pramipexole
      switched from an immediate-release formulation in patients with advanced
      Parkinson's disease: results from an open-label study.
AB  - This study aimed to evaluate the efficacy and safety of an extended-release
      tablet formulation of pramipexole (PPX-ER) given once daily when switched from an
      immediate-release tablet formulation (PPX-IR) given 3 times daily. This open
      label study included 29 patients with idiopathic Parkinson's disease (PD) who
      were followed for 8 weeks. Primary endpoints were Unified Parkinson's Disease
      Rating Scale (UPDRS) part III score, a physician evaluation of motor symptoms;
      nocturnal and early morning symptoms (NEMS) score, based on the results for 4
      items in the Parkinson's Disease Sleep Scale and the Movement Disorder Society -
      sponsored revision of the UPDRS; and patients' formulation preference, determined
      through questionnaires. Secondary endpoints were nocturnal sleep disturbance,
      evaluated using the revised version of the Parkinson's Disease Sleep Scale (PDSS
      2); quality of life, evaluated using the 39-item Parkinson's Disease
      Questionnaire (PDQ-39); Clinical Global Impression-Improvement (CGI-I) score;
      Patient Global Impression-Improvement (PGI-I) score; and caregiver formulation
      preference. UPDRS part III score (mean +/- SD) was significantly decreased after
      4 weeks (13.9 +/- 7.3; P=0.030) and 8 weeks (12.2 +/- 7.3; P<0.001) from baseline
      (15.3 +/- 7.0). However, no significant change was found in NEMS scale, PDSS-2 or
      PDQ-39 scores. After 8 weeks, the responder rates based on CGI-I and PGI-I scores
      were 27.6% and 20.7%, respectively. As a result of the questionnaire, 63.0% of
      patients and 58.8% of their caregivers preferred PPX-ER. A non-serious drug
      related adverse event (diarrhea) was observed in one patient. In conclusion, PPX
      ER can be considered as a useful treatment option when PPX-IR needs to be
      switched to other dopamine agonists.This study is registered with UMIN-CTR
      (UMIN000006521).

PMID- 23884662
TI  - Development and validation of RP-HPLC method for simultaneous estimation of
      glimepiride and sildenafil citrate in rat plasma-application to pharmacokinetic
      studies.
AB  - A simple and sensitive method was developed for simultaneous estimation of
      Glimepiride (GLIM) and Sildenafil citrate (SIL) in rat Plasma by reverse phase
      high performance liquid chromatography (RP-HPLC). The drug samples were extracted
      by liquid-liquid extraction with 300 ul of acetonitrile and 5 ml of diethyl
      ether. Chromatographic separation was achieved on C18 column using methanol:
      water (85:15 v/v) as mobile phase at a flow rate of 1 ml/min and UV detection at
      230 nm. The retention time of GLIM and SIL was found to be 2.5 and 4.0 min
      respectively with total run time of 7 min. The developed method was validated for
      accuracy, precision, linearity and recovery. The method was linear and found to
      be acceptable over the range of 100-12 000 ng/ml. The method was successfully
      applied for the analysis of rat plasma sample for application to pharmacokinetic.

PMID- 23884663
TI  - Alterations of the FSH and LH receptor genes and evaluation of sperm
      ultrastructure in men with idiopathic hypergonadotropic hypogonadism.
AB  - PURPOSE: Gonadotropins, interacting with their gonadal receptors, play a key role
      in sexual development, reproductive functions and metabolism. In this study we
      performed the genetic analysis of FSHR and LHR and semen investigation in 14
      infertile men with normal level of T and elevated levels of FSH and/or LH in the
      absence of other causes of infertility. METHODS: Sperm parameters were analysed
      following WHO (2010) guidelines and sperm morphology by Transmission Electron
      Microscopy (TEM) analysis mathematically elaborated. FSHR and LHR gene mutations
      have been searched by PCR technique, followed by DHPLC analysis and direct
      sequencing. RESULTS: In FSHR, we found no difference in the frequency between Ala
      or Thr at position 307, Ser was at codon 680 in all subjects. Three patients had
      an heterozygous mutation at codon 419. Three intronic polymorphisms (rs2091787,
      rs6708637, rs1922464) were significantly found compared to controls; the single
      allele frequency and the odds ratio were calculated. Two new variants: the
      Cys338Arg and the Gln123Glu were detected in two different patients. Regarding
      LHR, three patients were heterozygous for the known variant Glu354Lys and two for
      Ile374Thr. Intronic polymorphisms were not identified. A new variant, the
      Val144Ile was found. By the routine semen analysis, variable seminal conditions
      in this group of patients was observed, on the contrary TEM data mathematically
      elaborated showed a homogeneous decrease in fertility index and increase in sperm
      pathologies such as apoptosis and immaturity. CONCLUSIONS: The obtained results
      suggest that a deeper examination of spermatozoa, achieved by the use of more
      powerful tools such as TEM or molecular analysis, are advisable in patients with
      hypergonadotropic hypogonadism.

PMID- 23884664
TI  - Decomposition and nitrogen dynamics of (15)N-labeled leaf, root, and twig litter
      in temperate coniferous forests.
AB  - Litter nutrient dynamics contribute significantly to biogeochemical cycling in
      forest ecosystems. We examined how site environment and initial substrate quality
      influence decomposition and nitrogen (N) dynamics of multiple litter types. A 2.5
      year decomposition study was installed in the Oregon Coast Range and West
      Cascades using (15)N-labeled litter from Acer macrophyllum, Picea sitchensis, and
      Pseudotsuga menziesii. Mass loss for leaf litter was similar between the two
      sites, while root and twig litter exhibited greater mass loss in the Coast Range.
      Mass loss was greatest from leaves and roots, and species differences in mass
      loss were more prominent in the Coast Range. All litter types and species
      mineralized N early in the decomposition process; only A. macrophyllum leaves
      exhibited a net N immobilization phase. There were no site differences with
      respect to litter N dynamics despite differences in site N availability, and
      litter N mineralization patterns were species-specific. For multiple litter *
      species combinations, the difference between gross and net N mineralization was
      significant, and gross mineralization was 7-20 % greater than net mineralization.
      The mineralization results suggest that initial litter chemistry may be an
      important driver of litter N dynamics. Our study demonstrates that greater
      amounts of N are cycling through these systems than may be quantified by only
      measuring net mineralization and challenges current leaf-based biogeochemical
      theory regarding patterns of N immobilization and mineralization.

PMID- 23884666
TI  - Video-assisted thoracoscopic lobectomy for non-small cell lung cancer: a
      morbidity limiting approach in a patient on chronic hemodialysis and double agent
      antiplatelet therapy.
AB  - Patients with end-stage renal disease on hemodialysis undergoing surgery for lung
      cancer represent a high-risk group because of electrolyte imbalance, anemia,
      hemodynamic instability, bleeding tendency, and immunocompromised state. We
      describe a patient on hemodialysis with three lung adenocarcinoma of the right
      lower lobe as an incidental finding during the clinical course of a myocardial
      infarction treated with drug-eluting stent implantation and double-agent
      antiplatelet therapy. Considering patient comorbidities, we decided to perform a
      right lower lobectomy and complete lymph node dissection by a minimally invasive
      technique. In our experience, the thoracoscopic approach allowed us to perform
      lobectomy with complete lymph nodes dissection without morbidity. The use of
      ultrasound scalpel permits a complete lymph node dissection minimizing bleeding
      even in a double antiplatelet therapy patient. 

PMID- 23884667
TI  - Effects that different types of sports have on the hearts of children and
      adolescents and the value of two-dimensional strain-strain-rate echocardiography.
AB  - Whether the hypertrophy found in the hearts of athletes is physiologic or a risk
      factor for the progression of pathologic hypertrophy remains controversial. The
      diastolic and systolic functions of athletes with left ventricular (LV)
      hypertrophy usually are normal when measured by conventional methods. More
      precise assessment of global and regional myocardial function may be possible
      using a newly developed two-dimensional (2D) strain echocardiographic method.
      This study evaluated the effects that different types of sports have on the
      hearts of children and adolescents and compared the results of 2D strain and
      strain-rate echocardiographic techniques with conventional methods. Athletes from
      clubs for five different sports (basketball, swimming, football, wrestling, and
      tennis) who had practiced regularly at least 3 h per week during at least the
      previous 2 years were included in the study. The control group consisted of
      sedentary children and adolescents with no known cardiac or systemic diseases (n
      = 25). The athletes were grouped according to the type of exercise: dynamic
      (football, tennis), static (wrestling), or static and dynamic (basketball,
      swimming). Shortening fraction and ejection fraction values were within normal
      limits for the athletes in all the sports disciplines. Across all 140 athletes,
      LV geometry was normal in 58 athletes (41.4 %), whereas 22 athletes (15.7 %) had
      concentric remodeling, 20 (14.3 %) had concentric hypertrophy, and 40 (28.6 %)
      had eccentric hypertrophy. Global LV longitudinal strain values obtained from the
      average of apical four-, two-, and three-chamber global strain values were
      significantly lower for the basketball players than for all the other groups (p <
      0.001). 

PMID- 23884668
TI  - Effects of low-dose methotrexate in spinal cord injury in rats.
AB  - BACKGROUND: This study was designed to evaluate the possible protective effects
      of low-dose methotrexate in the spinal cord injury (SCI) in rats. METHODS: Thirty
      seven Wistar albino rats were used in the present study. Except for the animals
      of the Sham group, all animals were divided into two main groups, which were used
      in acute and subacute stage investigations. Then, thoracal laminectomy was
      performed, and except for the Sham group, SCI was induced using a temporary
      aneurysm clip. After clip compression, the experimental material (methotrexate or
      methylprednisolone) was administered intraperitoneally, except in the Sham and
      Control groups. Then, the spinal cords were removed to evaluate the SCI
      histopathologically and biochemically at the scheduled date. RESULTS: Neither
      experimental material was shown to reduce the histopathological grade in either
      stage of SCI. Low-dose methotrexate was shown to decrease lipid peroxidation
      levels only in the subacute stage of SCI. However, methylprednisolone and low
      dose methotrexate could not decrease or block myeloperoxidase enzyme activation
      in either stage of SCI. CONCLUSION: Low-dose methotrexate was effective in
      reducing the lipid peroxidation levels in the subacute stage of SCI, although
      histopathological evaluation results and myeloperoxidase levels of all groups did
      not support this finding at either stage.

PMID- 23884669
TI  - The effects of lornoxicam on brain edema and blood brain barrier following
      diffuse traumatic brain injury in rats.
AB  - BACKGROUND: In this experiment, the effects of lornoxicam on brain edema and the
      blood brain barrier (BBB) following diffuse traumatic brain injury (TBI) were
      studied. METHODS: Twenty adult male Wistar albino rats were anesthetized, and
      experimental closed head trauma was induced by the Marmarou method. After head
      injury, the rats were randomly divided into two groups: Group I was the control
      group, to which 2 ml saline was administered intraperitoneally, and Group II was
      the lornoxicam group, to which 2 ml 1.3 mg kg-1 lornoxicam was administered
      intraperitoneally. Twenty-four hours after head trauma, 99 mTc pentetate (DTPA)
      was injected at a dose of 37 MBq, and posterior planar images of each rat were
      obtained using an Infinia gamma camera. After imaging of BBB permeability, brain
      tissues were dissected from the cranium. The brain water content (BWC) of each
      sample was calculated using the wet-dry method. RESULTS: The lesion/background
      (L/b) ratio of Group I was 3.76+/-0.46 and 3.02+/-0.66 for early (5th min) and
      late (60th min) imaging, respectively. In Group II, the L/b ratios were 3.52+/
      0.96 and 2.63+/-0.63 for early and late imaging, respectively (p>0.05). BWC was
      79.6+/-2.5% and 77.5+/-1.1% for Groups I and II, respectively (p<0.05).
      CONCLUSION: In this rat model of TBI, lornoxicam reduced brain edema but did not
      affect BBB permeability.

PMID- 23884670
TI  - Genotoxicity of fixation devices analyzed by the frequencies of sister chromatid
      exchange.
AB  - BACKGROUND: Metal alloys utilized in the management of jaw fractures may exert
      genotoxic effects. Our purpose was to compare the genotoxicity of intermaxillary
      fixation devices containing nickel and chromium to that of titanium miniplates
      utilized in treatment of jaw fractures through the analysis of sister chromatid
      exchange. METHODS: In this prospective study, in a total of 28 non-smoker
      patients (10 females, 18 males; mean age 33.43+/-10.76; range 15 to 60 years)
      with jaw fractures, 14 were treated with intermaxillary fixation by
      administration of nickel-chromium wire and arch bar and 14 with titanium
      miniplates to investigate the genotoxicity of different metal alloys. The outcome
      variable was the frequency of sister chromatide exchange in peripheral
      lymphoctyes, determined through the analysis of venous blood samples obtained
      preoperatively and 4 to 6 weeks postoperatively. RESULTS: The frequency of the
      average sister chromatid exchange was found to be significantly higher in
      patients treated with the nickel-chromium intermaxillary fixation devices than
      those treated by titanium miniplates (1.29+/-0.29 vs. 0.46+/-0.39, p<0.001).
      CONCLUSION: Although titanium miniplate osteosynthesis is an invasive technique
      in comparison with the nickel-chromium-containing intermaxillary fixation
      devices, titanium seems to exert less genotoxic effect than the nickel-chromium
      alloy. However, this finding should be supported in clinical studies with a
      larger sampling size.

PMID- 23884671
TI  - [Effects of abdominal adhesion-preventing 4% icodextrin solution on healing of
      bowel anastomoses].
AB  - BACKGROUND: We aimed to introduce the efficiency of 4% icodextrin solution on
      preventing adhesions and its effect on anastomotic healing, together with
      biochemical parameters. METHODS: In total, 40 rats were divided into four groups
      of 10 rats each as Group A (abrasion+icodextrin), Group B (abrasion), Group C
      (anastomosis+icodextrin), and Group D (anastomosis). Adhesion grade, anastomotic
      bursting pressure, histopathological analysis, tissue hydroxyproline level, and
      serum myeloperoxidase (MPO), nitric oxide (NO), and malondialdehyde (MDA) values
      were examined. RESULTS: Adhesion score was significantly lower in Group A than in
      Group B and significantly lower in Group C than in Group D (p=0.003577,
      p=0.001612). No difference in anastomoses healing was determined between Group C
      and Group D (p=0.816). Hydroxyproline level was significantly higher in Group A
      than in Group B and significantly higher in Group C than in Group D (p=0.001,
      p=0.0001). There were no differences in NO and MDA levels between Group A and
      Group B, but values were significantly lower in Group C than in Group D (p=0.434,
      p=0.001, p=0.116, p=0.018). MPO level was significantly lower in Group A than in
      Group B and significantly lower in Group C than in Group D (p=0.0001, p=0.0001).
      CONCLUSION: Based on our results, 4% icodextrin solution evidently decreased the
      formation of adhesion without negatively affecting the anastomotic healing. We
      also reported herein the biochemical and histopathological results and adhesion
      scores.

PMID- 23884672
TI  - Effects of combined and individual use of N-methyl-D aspartate receptor
      antagonist magnesium sulphate and caspase-9 inhibitor z-LEDH-fmk in experimental
      spinal cord injury.
AB  - BACKGROUND: We investigated the individual and combined effects of magnesium
      sulphate, which is an N-Methyl-D aspartate receptor antagonist (NMDA), and z-LEHD
      FMK, which is a caspase 9 inhibitor, on the genesis of secondary injury in a rat
      spinal cord injury model. We aimed to minimize the effects of secondary injury in
      spinal cord trauma by choosing these two agents which served to block the two
      major mechanisms of cell loss, apoptosis and necrosis. METHODS: The drugs were
      given to the subjects according to their groups, either in singular or combined
      fashion. For motor examination, the subjects were kept under close clinical
      evaluation for five days. Histopathological examination and the emerging spinal
      cord samples were prepared with haematoxylene-eosin and Tunel techniques.
      RESULTS: A statistically significant difference in favor of the treatment groups
      has been found between the treatment and control groups in terms of histological
      data. However, there was no difference in the evaluation of motor examination
      between trauma and treatment groups. CONCLUSION: We have found no difference
      between the individual and combined uses of MgSO4 and z-LEHD-FMK in the
      prevention of secondary injury; however, there were better histological results
      in the treatment groups compared to trauma and control groups which gives us hope
      for future investigations.

PMID- 23884673
TI  - Analysis of appropriate tetanus prophylaxis in an Emergency Department.
AB  - BACKGROUND: In this study, our aim was to identify the validity of the
      prophylaxis indications for patients who received tetanus prophylaxis, determine
      the ratio of high-risk wounds to the number of patients with immunity, and to
      evaluate the tetanus immunity of specific age groups. METHODS: Patients who
      applied to the Emergency Department (ED) between September 2009 and May 2010 and
      who were considered for tetanus prophylaxis by his/her primary care physician
      were included in the study. RESULTS: A total of 320 patients were evaluated. The
      average age of the patients was 40.87 +/- 15.83 years. A total of 73.1% of the
      patients were male and 26.8% were female. A total of 40.3% of the patients knew
      their vaccination history, while 59.7% had no recollection of their vaccination
      history. 14.7% of the patients had received their last dose within 5 years and
      48.1% within 5-10 years; 37.2% of the patients declared that more 10 years had
      passed since their last vaccination. In 75% of the patients, the tetanus
      immunoglobulin (Ig)G level was identified as >=0.1 IU/ml, while 25% of the
      patients had levels <0.1 IU/ml. The number of patients with protective levels was
      lower among those who were illiterate or who had only a primary school education,
      and this difference was statistically significant (p<0.001). CONCLUSION: The
      vaccination histories can be misleading. Certain equipment can be used at the
      bedside to determine a patient's tetanus immunization status.

PMID- 23884674
TI  - [Impact of the practice of "Extended Focused Assessment with Sonography for
      Trauma" (e-FAST) on clinical decision in the emergency department].
AB  - BACKGROUND: We aimed to show the sensitivity of Extended Focused Assessment with
      Sonography for Trauma (e-FAST) for detection of pneumothorax, hemothorax and
      intraabdominal injury. We also investigated the relationship between e-FAST and
      need for invasive treatment. METHODS: This study included patients who
      experienced multiple trauma. The emergency physician, who had no clinical
      information about the patient, performed e-FAST. Findings on a supine chest X-ray
      and invasive interventions were recorded. The results of abdomen and thorax
      computed tomography (CT) were reviewed (the size of the pneumothorax was scored).
      RESULTS: Compared with CT, the sensitivities of e-FAST for intraabdominal injury
      and hemothorax were 54.5% and 71%, respectively. The patients with hemothorax and
      intraabdominal injuries were not identified with e-FAST, didn't need for invasive
      intervention. Pneumothorax diagnosis was established in 27 patients with e-FAST
      (sensitivity 81.8%) from among 33 (30.8%) pneumothorax patients. According to the
      grading on CT, pneumothoraces less than 1 cm in width and not exceeding the
      midcoronal line in length were not identified. e-FAST was positive for all
      patients performed with tube thoracostomy. CONCLUSION: e-FAST can be used with
      high sensitivity for determination of pneumothorax requiring invasive procedure.
      It has low sensitivity in the diagnosis of intraabdominal injury and hemothorax;
      however, e-FAST can predict the need for invasive procedures.

PMID- 23884675
TI  - Treatment of acute scrotum in children: 5 years' experience.
AB  - BACKGROUND: A retrospective review was carried out to determine the incidence of
      various causes and outcome of management in patients with acute scrotum. METHODS:
      Fifty children had a diagnosis of acute scrotum between 1st January 2007 and 15th
      May 2012. Age, mode of presentation, associated anomalies, and results of
      treatment were studied. Diagnosis of acute scrotum was confirmed by physical
      examination, Doppler ultrasound and biochemical investigations. RESULTS: Clinical
      presentation consisted of sudden swelling and pain in the inguinoscrotal region.
      The average age was 7.5 years (2 months-14 years). Causes of acute scrotum were
      orchitis/epididymo-orchitis (O /EO) in 22, strangulated inguinal hernia (SIH) in
      16, testicular torsion (TT) in 11, and torsion of testicular appendage (TTA) in
      1. Associated urological anomalies were found in 5 patients with O /EO. Medical
      treatment was applied to patients with O /EO, and surgical treatment was
      performed in patients with SIH, TT and TTA. CONCLUSION: In this series, O /EO was
      found to rank first as the cause of acute scrotum. Immediate surgical treatment
      in acute scrotum patients, except those with O /EO, is necessary. Associated
      urological anomalies should be investigated in patients with O /EO.

PMID- 23884676
TI  - Non-operative treatment approach for blunt splenic injury: is grade the unique
      criterion?
AB  - BACKGROUND: We aimed to investigate the results of a non-operative approach to
      blunt spleen injury to re-evaluate the importance of injury grade. METHODS:
      Thirty-one blunt splenic trauma cases subjected to non-operative treatment were
      evaluated retrospectively. The patients were classified into two groups as
      isolated spleen trauma (ST) group and multi-trauma (MT) group. The
      hospitalization and blood replacement needs, success of non-operative follow-up,
      and post-traumatic complications were compared between the two groups. The
      patients were evaluated via follow-up abdominal ultrasonography (US) and
      computerized tomography (CT). The results were evaluated with regard to post
      splenic trauma complications. RESULTS: According to the organ injury scale of the
      American Association for the Surgery of Trauma, 25.8% were grade-1, 32.2% grade
      2, 29% grade-3, and 12.9% grade-4 injuries. It was observed that the transfusion
      amount was directly proportional to the injury grade. All patients with grade-4
      injury and 14 patients with MT were treated successfully with the non-operative
      method. Splenic pseudoaneurysm developed in one patient in the MT group. One
      patient was diagnosed with late splenic rupture. CONCLUSION: Hemodynamic
      stability is the most important criterion for the indication of non-operative
      treatment. However, in well-selected cases, patients with grade 4 splenic traumas
      and those with extra-splenic injuries could also be treated successfully with the
      non-operative method.

PMID- 23884677
TI  - Thoracic aortic aneurysms after blunt trauma.
AB  - BACKGROUND: Aortic injury after blunt trauma that is missed during the first
      admission will soon be seen as a chronic aneurysm. The objective of this study is
      to show the importance of the diagnosis and appropriate treatment of these
      aneurysms. METHODS: Between 2009 and 2012, 8 patients (mean age, 50+/-31 years)
      diagnosed with chronic traumatic aortic aneurysm were treated with either
      thoracic endovascular aortic repair (TEVAR) or conventional surgery 20 years on
      average after the trauma. RESULTS: Treatments included TEVAR in four patients,
      conventional surgery in two patients, and hybrid intervention in one patient. One
      patient died postoperatively. One patient had an endoleak requiring a repeat
      TEVAR, which was successful. Brachial embolectomy was performed after placing the
      endovascular stent. No paraplegia or lower extremity ischemia was seen. One
      patient died preoperatively due to rupture of the aneurysm. CONCLUSION: Chronic
      traumatic aortic aneurysms may cause general symptoms years after a blunt trauma.
      Aortic injury must always be considered in the assessment and follow-up of trauma
      patients.

PMID- 23884678
TI  - Fractures of the mandible: a 20-year retrospective analysis of 753 patients.
AB  - BACKGROUND: The craniofacial region is one of the most frequently injured parts
      of the body, and mandibular fracture is one of the commonest facial skeletal
      injuries. The most frequent causes of mandibular fractures are the traumas
      related to traffic accidents, falls, interpersonal violence, and sports
      activities, etc. METHODS: Seven hundred fifty-three cases (615 male, 138 female;
      megan age 36.2 years) (age >16) with mandibular fracture were evaluated
      retrospectively. Patient records were examined in terms of age, sex, etiology,
      seasonal variation, fracture localization, accompanying traumas, treatment
      modality, and postoperative complications. RESULTS: Traffic accidents were the
      most common etiologic cause in all age groups and both sexes. All cases had a
      total of 1090 fractures, and the most common fracture localization was the
      parasymphysis (28.6%), followed by the condyle, corpus, angulus, symphysis,
      dentoalveolar process, ramus, and coronoid process, respectively. In 25 (3.3%)
      patients with fissure-like, non-displaced fracture, only symptomatic treatment
      was applied. Closed reduction with elastic bandage, arch bar, quick-fix screws or
      Ivy Loop was the only method performed in 280 (37.2%) patients. Osteosynthesis by
      open reduction and internal fixation (miniplates, screws or transosseous wiring)
      was performed in 403 (53.5%) patients; closed reduction techniques were also
      performed in 134 of these patients. CONCLUSION: In the recent years, double-road
      constructions, increased traffic audits and regulation of the traffic rules
      decreased the incidence of mandibular fractures.

PMID- 23884679
TI  - Demographic and etiologic characteristics of children with traumatic serious
      hyphema.
AB  - BACKGROUND: We aimed to evaluate the etiologic factors, complications, follow-up,
      and treatment outcomes in serious hyphema following blunt ocular trauma in
      childhood. METHODS: The medical records of 136 patients diagnosed as grade 3 or 4
      hyphema due to blunt ocular trauma between January 2006 and December 2011 were
      evaluated. Visual acuity (VA), complications, and medical and surgical treatments
      were analyzed. Factors affecting visual prognosis were compared in grade 3 and 4
      hyphema cases. RESULTS: The mean age of patients was 9.7+/-4 years. Etiologic
      factors for trauma were stone in 53 (39%), bead bullet in 25 (18.4%) and others
      in 58 (42.6%) patients. The most common complication of grade 3 and 4 hyphema was
      traumatic mydriasis (19.1%), followed by cataract (9.6%) and glaucoma (5.1%).
      Medical treatment was successful in 114 (83.8%) patients, and 22 (16.2%) patients
      underwent surgery. Mean initial and final VA of grade 4 patients were found to be
      significantly lower than those of grade 3 patients. CONCLUSION: In grade 3 and 4
      hyphema due to blunt trauma, visual prognosis worsened in the presence of
      additional ocular pathologies. Considering the bad visual prognosis of severe
      hyphema patients, prompt treatment and close follow-up may prevent complications
      resulting in poor VA.

PMID- 23884680
TI  - [A rare complication of blunt trauma; diaphragm-pericardium rupture and cardiac
      herniation in a child case].
AB  - Diaphragma and pericardium rupture is rarely seen after blunt trauma. It's
      treatment is surgery. A 4-year-old male patient who was operated for diaphragm
      and pericardium rupture which developed after blunt trauma; rarity of this union,
      differences in the clinical and radiological features in children was examined. 

PMID- 23884681
TI  - Traumatic renal artery occlusion in the pediatric age group: a case and review of
      the literature.
AB  - Blunt trauma represents a major cause of death in children. The incidence of
      renal arterial injuries in these cases is less than 1%. Traumatic renal artery
      occlusion is a rare occurrence in the pediatric age group. However, there is lack
      of information on the exact incidence and results of the management of these rare
      cases in the pediatric age group. We report herein a case and we review the
      available literature of this severe injury in the pediatric age group. 

PMID- 23884682
TI  - [Residual pellet in fetal brain tissue following a gunshot injury to a pregnant
      woman: a case report].
AB  - Vital functions and the effect of injuries on quality of life are important from
      a viewpoint of causation in willful injury crimes committed against a pregnant
      woman. In such conditions, which should be evaluated separately in criminal law
      and compensation law, permanent losses of organ function that may negatively
      affect the woman's fertility, the features of permanent functional impairments
      and premature birth of the fetus can be additive factors for the indemnification
      amount. In scientific literature, case reports addressing the morphological and
      physiological changes to the fetus due to firearm injury are rare. In the
      presented case, we aimed to evaluate the fetus's situation, following firearm
      injury to a 41-year-old woman at 27 weeks gestation. While the mother was living
      a healthy life, the significant problem of the child in the first four-year
      period of his development was hyperactivity. Evaluating the effect of the frontal
      lobe lesion on the psychiatric findings of the child is important. 

PMID- 23884683
TI  - Bouveret syndrome: evaluation with multidetector computed tomography and contrast
      enhanced magnetic resonance cholangiopancreatography.
AB  - Cholecystenteric fistula is one of the rarest complications of biliary lithiasis,
      with a frequency of less than 1%. Bouveret syndrome is a gastric outlet
      obstruction produced by gallstone(s) located in the distal stomach or proximal
      duodenum. The route of gallstone migration to the bowel is most commonly via a
      cholecystoduodenal fistula; however, fistulization of the stomach is a rarer
      variation. Early diagnosis of this situation is crucial to reduce morbidity and
      mortality. In this report, we present a patient with cholecystogastric fistula
      and Bouveret syndrome. To our knowledge, there is no published paper in the
      literature related to the diagnosis of Bouveret syndrome with multidetector
      computed tomography (MDCT) (64 detectors) and/or contrast-enhanced magnetic
      resonance cholangiopancreatography (CE-MRCP). Our aim was to discuss the efficacy
      of MDCT and CE-MRCP in the detection and evaluation of cholecystenteric fistulas.
      We showed the exact localization and relation of biliary stones and the fistula
      by MDCT and CE-MRCP. We also evaluated the biliary system with CE-MRCP
      physiologically. In conclusion, when biliary lithiasis and ileus are detected in
      plain radiography, the first-line diagnostic tool should be MDCT. In complicated
      cases or when biliary obstruction is suspected, CE-MRCP can give important
      morphological and physiological information regarding the whole abdomen and
      biliary system. 

PMID- 23884684
TI  - De Garengeot's hernia: a case of acute appendicitis in a femoral hernia sac.
AB  - The presence of an appendix vermiformis in a femoral hernia sac is called De
      Garengeot's hernia. It is a very rare clinical condition and requires emergency
      surgery. However, preoperative diagnosis of De Garengeot's hernia is difficult.
      Herein, we report a 58-year-old female who presented with sudden-onset painful
      swelling in the right groin region. Diagnosis was established based on computed
      tomography findings, and appendectomy with mesh-free hernia repair was performed.
      The postoperative period was uneventful, and the histopathologic examination of
      the specimen revealed gangrenous appendicitis. 

PMID- 23884685
TI  - Severe burn on 81% of body surface after sun tanning.
AB  - We report herein the case of a 42-year-old woman who presented to the Burns Unit
      with 81% of her body surface severely burned following sun bathing, after
      applying fig leaf tea as a tanning agent. The patient was hospitalized for 13
      days in a Burns Intensive Care Unit, and was discharged for an ambulatory follow
      up. The treatment of such burns does not differ from any conventional treatment
      for heat- induced second-degree burns. The physiopathology of the
      phytophotodermatitis induced by such homemade tanning solutions rich in psoralen
      is discussed in detail. 

PMID- 23884686
TI  - An extremely rare appendiceal anomaly: horseshoe appendicitis.
AB  - Appendiceal anomalies are extremely rare malformations that are usually found in
      adult populations as an incidental finding. Agenesis and duplication of the
      appendix have been well documented, but we know of only three reported cases of a
      horseshoe appendix. A 64-year-old woman admitted to the emergency department. A
      provisional diagnosis of acute appendicitis was made, and the patient was taken
      to the operating room. While appendectomy was being performed with a standard
      approach, the distal tip was seen to communicate with the cecum by another stump,
      or "horseshoe appendix". The aim of this report is to share our experience with
      this extraordinary finding. 

PMID- 23884687
TI  - A taxonomy of inductive problems.
AB  - Inductive inferences about objects, features, categories, and relations have been
      studied for many years, but there are few attempts to chart the range of
      inductive problems that humans are able to solve. We present a taxonomy of
      inductive problems that helps to clarify the relationships between familiar
      inductive problems such as generalization, categorization, and identification,
      and that introduces new inductive problems for psychological investigation. Our
      taxonomy is founded on the idea that semantic knowledge is organized into systems
      of objects, features, categories, and relations, and we attempt to characterize
      all of the inductive problems that can arise when these systems are partially
      observed. Recent studies have begun to address some of the new problems in our
      taxonomy, and future work should aim to develop unified theories of inductive
      reasoning that explain how people solve all of the problems in the taxonomy. 

PMID- 23884688
TI  - Recollection can support hybrid visual memory search.
AB  - On a daily basis, we accomplish the task of searching our visual environment for
      one of a number of possible objects, like searching for any one of our friends in
      a crowd, and we do this with ease. Understanding how attention, perception, and
      long-term memory interact to accomplish this process remains an important
      question. Recent research (Wolfe in Psychological Science 23:698-703, 2012) has
      shown that increasing the number of possible targets one is searching for adds
      little cost to the efficiency of visual search-specifically, that response times
      increase logarithmically with memory set size. It is unclear, however, what type
      of recognition memory process (familiarity or recollection) supports a hybrid
      visual memory search. Previous hybrid search paradigms create conditions that
      allow participants to rely on the familiarity of perceptually identical targets.
      In two experiments, we show that hybrid search remains efficient even when the
      familiarity of targets is minimized (Experiment 1) and when participants are
      encouraged to flexibly retrieve target information that is perceptually distinct
      from the information previously studied (Experiment 2). We propose that such
      efficient and flexible performance on a hybrid search task may engage a rapid
      from of recollection (Moscovitch in Canadian Journal of Experimental Psychology
      62:62-79, 2008). We discuss possible neural correlates supporting simultaneous
      perception, comparison of incoming information, and recollection of episodic
      memories. 

PMID- 23884689
TI  - Assessing the costs and benefits of production in recognition.
AB  - The production effect is a memory advantage for items studied aloud over items
      studied silently. Although it typically is found within subjects, here we also
      obtained it between subjects in a recognition task-providing new evidence that
      production can be an effective study strategy. Our experiment, and a set of meta
      analyses, also evaluated whether the within effect reflects costs to silent items
      and/or benefits to aloud items. Contrary to a strong distinctiveness account, we
      found little evidence that aloud items show an additional within-subjects
      benefit. Instead, silent items suffered an additional within-subjects cost.
      Blocking silent and aloud items eliminated this cost, suggesting that the cost
      was due to mixing silent and aloud items. Our discussion focuses on implications
      for distinctiveness and strength accounts of the production effect and on how to
      implement production as an encoding strategy depending on the learner's goals. 

PMID- 23884690
TI  - Unexpected downshifts in reward magnitude induce variation in human behavior.
AB  - We investigated how changes in outcome magnitude affect behavioral variation in
      human volunteers. Our participants entered strings of characters using a computer
      keyboard, receiving feedback (gaining a number of points) for any string at least
      ten characters long. During a "surprise" phase in which the number of points
      awarded was changed, participants only increased their behavioral variability
      when the reward value was downshifted to a lower amount, and only when such a
      shift was novel. Upshifts in reward did not have a systematic effect on
      variability.

PMID- 23884691
TI  - Training and the attentional blink: limits overcome or expectations raised?
AB  - The attentional blink (AB) refers to a deficit in reporting the second of two
      sequentially presented targets when they are separated by less than 500 ms. Two
      decades of research has suggested that the AB is a robust phenomenon that is
      likely attributable to a fundamental limit in sequential object processing. This
      assumption, however, has recently been undermined by a demonstration that the AB
      can be eliminated after only a few hundred training trials (Choi, Chang, Shibata,
      Sasaki, & Watanabe in Proceedings of the National Academy of Sciences 109:12242
      12247, 2012). In the present work, we examined whether this training benefited
      performance directly, by eliminating processing limitations as claimed, or
      indirectly, by creating expectations about when targets would appear. Consistent
      with the latter option, when temporal expectations were reduced, training-related
      improvements declined significantly. This suggests that whereas training may
      ameliorate the AB indirectly, the processing limits evidenced in the AB cannot be
      directly eliminated by brief exposure to the task.

PMID- 23884692
TI  - Convergence to a pulsating travelling wave for an epidemic reaction-diffusion
      system with non-diffusive susceptible population.
AB  - In this work we study the asymptotic behaviour of the Kermack-McKendrick reaction
      diffusion system in a periodic environment with non-diffusive susceptible
      population. This problem was proposed by Kallen et al. as a model for the spatial
      spread for epidemics, where it can be reasonable to assume that the susceptible
      population is motionless. For arbitrary dimensional space we prove that large
      classes of solutions of such a system have an asymptotic spreading speed in large
      time, and that the infected population has some pulse-like asymptotic shape. The
      analysis of the one-dimensional problem is more developed, as we are able to
      uncover a much more accurate description of the profile of solutions. Indeed, we
      will see that, for some initially compactly supported infected population, the
      profile of the solution converges to some pulsating travelling wave with minimal
      speed, that is to some entire solution moving at a constant positive speed and
      whose profile's shape is periodic in time. 

PMID- 23884693
TI  - Dietary L-glutamine supplementation increases Pasteurella multocida burden and
      the expression of its major virulence factors in mice.
AB  - This study was conducted to determine the effects of graded doses of L-glutamine
      supplementation on the replication and distribution of Pasteurella multocida, and
      the expression of its major virulence factors in mouse model. Mice were randomly
      assigned to the basal diet supplemented with 0, 0.5, 1.0 or 2.0 % glutamine.
      Pasteurella multocida burden was detected in the heart, liver, spleen, lung and
      kidney after 12 h of P. multocida infection. The expression of major virulence
      factors, toll-like receptors (TLRs), proinflammatory cytokines (interleukin-1
      beta, interleukin-6, and tumor necrosis factor alpha) and anti-oxidative factors
      (GPX1 and CuZnSOD) was analyzed in the lung and spleen. Dietary 0.5 % glutamine
      supplementation has little significant effect on these parameters, compared to
      those with basal diet. However, results showed that a high dose of glutamine
      supplementation increased the P. multocida burden (P < 0.001) and the expression
      of its major virulence factors (P < 0.05) as compared to those with a lower dose
      of supplementation. In the lung, high dose of glutamine supplementation inhibited
      the proinflammatory responses (P < 0.05) and TLRs signaling (P < 0.05). In the
      spleen, the effect of glutamine supplementation on different components in TLR
      signaling depends on glutamine concentration, and high dose of glutamine
      supplementation activated the proinflammatory response. In conclusion, glutamine
      supplementation increased P. multocida burden and the expression of its major
      virulence factors, while affecting the functions of the lung and spleen. 

PMID- 23884694
TI  - Elevated ornithine decarboxylase activity promotes skin tumorigenesis by
      stimulating the recruitment of bulge stem cells but not via toxic polyamine
      catabolic metabolites.
AB  - Elevated expression of ornithine decarboxylase (ODC), the regulatory enzyme in
      polyamine biosynthesis, targeted to the epidermis is sufficient to promote skin
      tumor development following a single subthreshold dose of
      dimethylbenz(a)anthracene (DMBA). Since skin tumor promotion involves recruitment
      of hair follicle bulge stem cells harboring genetic lesions, we assessed the
      effect of increased epidermal ODC on recruitment of bulge stem cells in ODC-ER
      transgenic mice in which ODC activity is induced de novo in adult skin with 4
      hydroxytamoxifen (4OHT). Bromodeoxyuridine-pulse labeling and use of
      K15.CrePR1;R26R;ODC-ER triple transgenic mice demonstrated that induction of ODC
      activity is sufficient to recruit bulge stem cells in quiescent skin. Because
      increased ODC activity not only stimulates proliferation but also increases
      reactive oxygen species (ROS) generation via subsequent induction of polyamine
      catabolic oxidases, we used an inhibitor of polyamine catabolic oxidase activity,
      MDL72527, to investigate whether ROS generation by polyamine catabolic oxidases
      contributes to skin tumorigenesis in DMBA-initiated ODC-ER transgenic skin.
      Newborn ODC-ER transgenic mice and their normal littermates were initiated with a
      single topical dose of DMBA. To assess tumor development originating from dormant
      bulge stem cells that possess DMBA-initiated mutations, epidermal ODC activity
      was induced in ODC-ER mice with 4OHT 5 weeks after DMBA initiation followed by
      MDL72527 treatment. MDL72527 treatment resulted in a shorter tumor latency time,
      increased tumor burden, increased conversion to carcinomas, and lower tumor
      levels of p53. Thus, elevated epidermal ODC activity promotes tumorigenesis by
      stimulating the recruitment of bulge stem cells but not via ROS generation by
      polyamine catabolic oxidases. 

PMID- 23884695
TI  - The incidence of postoperative endophthalmitis after cataract surgery in China: a
      multicenter investigation of 2006-2011.
AB  - AIMS: To estimate the cumulative incidence of postoperative endophthalmitis,
      identify risk factors and determine clinical outcomes in China. METHODS: Medical
      records were reviewed for all patients with acute-onset endophthalmitis after
      cataract surgery from January 2006 to December 2011 at eight eye centres of
      tertiary care hospitals in China. RESULTS: Sixty-six cases of presumed
      endophthalmitis occurred after 201 757 cataract surgeries, yielding a cumulative
      incidence of 0.033% (95% CI 0.025 to 0.041). Logistic regression analysis
      revealed that the risk of endophthalmitis increased with intraoperative
      communication with vitreous (multivariate OR 9.96; 95% CI 4.54 to 21.84;
      p<0.001). After a median follow-up of 153 days, best-corrected visual acuity in
      the affected eye was more than 20/70 in 29/65 (44.6%) patients, and more than
      20/40 in 20/65 (30.8%). A predictor of good visual acuity was baseline acuity of
      counting fingers or better (OR 6.25; 95% CI 2.13 to 18.33). Of 64 cases, 25
      (39.1%) were culture positive. Coagulase-negative Staphylococcus and Pseudomonas
      species were the most common organisms isolated, accounting for 72.0% of the
      culture-positive cases (18/25). Two eye centres that used a combination of a high
      concentration vancomycin (1 mg/0.1 mL intracameral vancomycin injection or 100
      ug/mL vancomycin in irrigating solution) and tobramycin as infection prophylaxis
      achieved a lower incidence of endophthalmitis than other centres (p<0.001).
      CONCLUSIONS: The incidence of acute postoperative endophthalmitis after cataract
      surgery in tertiary care hospitals of China was 0.033%. Intraoperative
      communication with vitreous was a major risk factor for developing
      endophthalmitis. Prophylactic use of a high-concentration vancomycin and
      tobramycin may play a positive role in the prevention of postoperative
      endophthalmitis after cataract surgery.

PMID- 23884696
TI  - Inflammatory status as a major role of risk factor for atrial fibrillation.

PMID- 23884697
TI  - The parents', hospitalized child's, and health care providers' perceptions and
      experiences of family centered care within a pediatric critical care setting: a
      metasynthesis of qualitative research.
AB  - The delivery of family centered care (FCC) occurs within varied pediatric care
      settings with a belief that this model of care meets the psychosocial, emotional,
      and physical needs of the hospitalized child and family. The aim of this review
      was to explore the attitudes, experiences, and implementation of FCC from many
      studies and to facilitate a wider and more thorough understanding of this
      practice from a diverse sample of parents, hospitalized children, and their
      health care providers within a pediatric critical care setting. A metasynthesis
      is an integration of qualitative research findings based on a systematic review
      of the literature. Thirty original research articles focusing on family-centered
      care experiences from the hospitalized child's, parents', and health care
      providers' perception published between 1998 and 2011 met the criteria for the
      review. Nine syntheses from 17 themes emerged from the synthesis of the
      literature: Prehospital, Entry into the Hospital, Journeying Through Unknown
      Waters, Information, Relationships, The hospital Environment, The Possibility of
      Death, Religion and Spirituality, and The Journey Home. The individual cultures
      of the critical care units helped create and reinforce the context of parental
      needs where satisfaction with communication, information, and relationships were
      interconnecting factors that helped maintain the positive or negative experiences
      for the parent, hospitalized child, and/or health care providers. 

PMID- 23884698
TI  - Determination of AM-2201 metabolites in urine and comparison with JWH-018 abuse.
AB  - With respect to the continuous emergence of new synthetic cannabinoids on the
      market since 2008, evaluation of the metabolism of these compounds and the
      development of analytical methods for the detection of these drugs including
      their respective metabolites in biological fluids have become essential. Other
      than JWH-018 or JWH-073, AM-2201 is one of the frequently identified synthetic
      cannabinoids in Korea. Recently, in our laboratory, several JWH-018 metabolites
      have been detected in some urine samples obtained from subjects who were arrested
      for the possession of herbal mixtures containing only AM-2201 or from those who
      confessed AM-2201 abuse. In the present study, we identified major urinary
      metabolites of AM-2201 and several metabolites of JWH-018, i.e., N-5-hydroxylated
      and carboxylated metabolites from rats administered AM-2201 and found that the
      metabolic profile in rats was similar to those in human subjects in this study.
      Analytical results of the urine samples from suspects who had a considerable
      possibility of AM-2201 or JWH-018 intake were also compared to distinguish
      between AM-2201 and JWH-018 abuse. The presence of 6-indole hydroxylated
      metabolites of each drug and N-4-hydroxy metabolite of AM-2201 was found to
      contribute to the decisive differences in the metabolic patterns of the two
      drugs. In addition, the concentration ratio of the N-(5-hydroxypentyl) metabolite
      to the N-(4-hydroxypentyl) metabolite of JWH-018 may be used as a criterion to
      differentiate between AM-2201 and JWH-018 abuse. 

PMID- 23884699
TI  - Promoting cooperative federalism through state shared savings.
AB  - The Affordable Care Act is transforming American federalism and creating strain
      between the states and the federal government. By expanding the scale of
      intergovernmental health programs, creating new state requirements, and setting
      the stage for increased federal fiscal oversight, the act has disturbed an uneasy
      truce in American federalism. This article outlines a policy proposal designed to
      harness cooperative federalism, based on the shared state and federal desire to
      control health care cost growth. The proposal, which borrows features of the
      Medicare Shared Savings Program, would provide states with an incentive in the
      form of an increased share of the savings they generate in programs that have
      federal financial participation, as long as they meet defined performance
      standards. 

PMID- 23884700
TI  - Bradycardia: changes in intrinsic rate rather than cardiac autonomic modulation.

PMID- 23884701
TI  - 18F-FDG PET/CT of a rectal carcinoma and a sigmoid adenoma.

PMID- 23884702
TI  - The brain is not a tool.
AB  - Some psychologists claim that the brain is a tool. This claim can be construed
      either literally or figuratively. We argue that, in the former case, it is false,
      whereas in the latter case it has no place in scientific psychology. We also try
      to show why this discussion is relevant and suggest how a metaphor should behave
      to be of use in science. 

PMID- 23884703
TI  - Community-wide job loss and teenage fertility: evidence from North Carolina.
AB  - Using North Carolina data for the period 1990-2010, we estimate the effects of
      economic downturns on the birthrates of 15- to 19-year-olds, using county-level
      business closings and layoffs as a plausibly exogenous source of variation in the
      strength of the local economy. We find little effect of job losses on the white
      teen birthrate. For black teens, however, job losses to 1 % of the working-age
      population decrease the birthrate by around 2 %. Birth declines start five months
      after the job loss and then last for more than one year. Linking the timing of
      job losses and conceptions suggests that black teen births decline because of
      increased terminations and perhaps also because of changes in prepregnancy
      behaviors. National data on risk behaviors also provide evidence that black teens
      reduce sexual activity and increase contraception use in response to job losses.
      Job losses seven to nine months after conception do not affect teen birthrates,
      indicating that teens do not anticipate job losses and lending confidence that
      job losses are "shocks" that can be viewed as quasi-experimental variation. We
      also find evidence that relatively advantaged black teens disproportionately
      abort after job losses, implying that the average child born to a black teen in
      the wake of job loss is relatively more disadvantaged.

PMID- 23884704
TI  - Sero-prevalence and risk factors study of brucellosis in small ruminants in
      Southern Zone of Tigray Region, Northern Ethiopia.
AB  - This study reports a prevalence and risk factor survey of brucellosis in small
      ruminants in Southern Zone of Tigray Region, Northern Ethiopia between October
      2011 and April 2012 to determine the sero-prevalence of small-ruminant
      brucellosis and to identify associated risk factors for the occurrence of disease
      in small ruminants under extensive production system. Multistage random sampling
      was followed to select locations, flocks, and individual animals. Laboratory
      analysis of serum samples provided sero-prevalence estimates for flocks and
      geographic location. Information on risk factors at the individual and flock
      level was obtained by examination of individual animal and a questionnaire
      interview to flock owners. The overall individual animal-level sero-prevalence of
      brucellosis in small ruminants was 3.5 % and flock level sero-prevalence was 28.3
      %, and the within-flock sero-prevalence was ranged from 0 % to 22.2 % based on
      the Complement Fixation Test. Multivariable logistic regression showed that the
      major risk factors for flock level sero-positivity were flock size and abortion
      history. This study showed that small-ruminant brucellosis is prevalent in the
      study area. Larger flock size and history of previous abortion in the flock were
      major risk factors identified for sero-positivity of small-ruminant brucellosis. 

PMID- 23884705
TI  - Validation of the 2010 American College of Rheumatology preliminary diagnostic
      criteria for fibromyalgia in an Iranian population.
AB  - The aim of this study was to validate the 2010 American College of Rheumatology
      (ACR) preliminary criteria for fibromyalgia (FM) in an Iranian population. In
      this multicenter prospective study, we enrolled 168 FM patients and 110 controls.
      All participants underwent dolorimetry examination by study assessors and
      completed a questionnaire containing variables of both the ACR 2010 preliminary
      and ACR 1990 criteria. We compared the performance of the ACR 2010 criteria with
      the expert diagnosis as well as the ACR 1990 criteria. Receiver operator
      characteristic analyses and Youden index were used to evaluate the test
      characteristics of a set of different cutoff points for two subcomponents of ACR
      2010 criteria including widespread pain index (WPI) and symptom severity (SS)
      scale. Considering expert diagnosis as the gold standard, the ACR 2010 criteria
      showed comparable specificity with ACR 1990 (92.8 vs. 88.3 %, P = 0.073), but
      lower sensitivity (58.9 vs. 71.4 %, P = 0.003) and a tendency for lower accuracy
      (72.4 vs. 78.4 %, P = 0.105). Applying the ACR 1990 criteria as the gold
      standard, we observed a trend toward an increase in overall accuracy (72.4 vs.
      79.1 %, P = 0.064). Optimal test characteristics were achieved for WPI >=6 and SS
      scale score >=4 and improved sensitivity and accuracy of ACR 2010 criteria when
      compared to expert, 76.1 and 81.7, respectively. The preliminary ACR 2010
      criteria performed less desirably in terms of sensitivity in our set of Iranian
      patients. Selecting lower cutoff points as WPI >=6 and SS scale score >=4
      improved the diagnostic values of the criteria.

PMID- 23884706
TI  - From data point timelines to a well curated data set, data mining of experimental
      data and chemical structure data from scientific articles, problems and possible
      solutions.
AB  - The scientific literature is important source of experimental and chemical
      structure data. Very often this data has been harvested into smaller or bigger
      data collections leaving the data quality and curation issues on shoulders of
      users. The current research presents a systematic and reproducible workflow for
      collecting series of data points from scientific literature and assembling a
      database that is suitable for the purposes of high quality modelling and decision
      support. The quality assurance aspect of the workflow is concerned with the
      curation of both chemical structures and associated toxicity values at (1) single
      data point level and (2) collection of data points level. The assembly of a
      database employs a novel "timeline" approach. The workflow is implemented as a
      software solution and its applicability is demonstrated on the example of the
      Tetrahymena pyriformis acute aquatic toxicity endpoint. A literature collection
      of 86 primary publications for T. pyriformis was found to contain 2,072 chemical
      compounds and 2,498 unique toxicity values, which divide into 2,440 numerical and
      58 textual values. Every chemical compound was assigned to a preferred toxicity
      value. Examples for most common chemical and toxicological data curation
      scenarios are discussed. 

PMID- 23884707
TI  - Pyridones as NNRTIs against HIV-1 mutants: 3D-QSAR and protein informatics.
AB  - CoMFA and CoMSIA based 3D-QSAR of HIV-1 RT wild and mutant (K103, Y181C, and
      Y188L) inhibitory activities of 4-benzyl/benzoyl pyridin-2-ones followed by
      protein informatics of corresponding non-nucleoside inhibitors' binding pockets
      from pdbs 2BAN, 3MED, 1JKH, and 2YNF were analysed to discover consensus features
      of the compounds for broad-spectrum activity. The CoMFA/CoMSIA models indicated
      that compounds with groups which lend steric-cum-electropositive fields in the
      vicinity of C5, hydrophobic field in the vicinity of C3 of pyridone region and
      steric field in aryl region produce broad-spectrum anti-HIV-1 RT activity. Also,
      a linker rendering electronegative field between pyridone and aryl moieties is
      common requirement for the activities. The protein informatics showed
      considerable alteration in residues 181 and 188 characteristics on mutation.
      Also, mutants' isoelectric points shifted in acidic direction. The study offered
      fresh avenues for broad-spectrum anti-HIV-1 agents through designing new
      molecules seeded with groups satisfying common molecular fields and concerns of
      mutating residues. 

PMID- 23884708
TI  - Familial breast cancer genetic testing in the West of Ireland.
AB  - AIMS: The majority of hereditary breast and ovarian cancers are associated with
      highly penetrant mutations in two genes: BRCA 1 and 2. Our aim was to investigate
      the prevalence and types of BRCA mutations in patients from the West of Ireland.
      METHODS: A retrospective cohort study was undertaken that included all patients
      from the counties, Mayo, Sligo, Galway, Roscommon, and Clare, who were referred
      to the National Centre for Medical Genetics (NCMG) for testing for mutations in
      BRCA 1 or 2 between 2000 and 2010. Data including age, symptoms, family history,
      Manchester score, and test results were recorded and analysed using SPSS.
      RESULTS: The NCMG received 380 referrals from the Western seaboard, including 148
      for diagnostic testing and 232 for predictive evaluation. Sixty-five patients did
      not attend for assessment. Two hundred and fifty-six patients fulfilled criteria
      for genetic counselling, which was accepted by 184, of whom 127 proceeded to
      testing. Predictive tests were more often declined than diagnostic [41 (46 %) vs.
      16 (17 %)]. Ten mutations in BRCA 1 were identified in 20 patients (15 families),
      including Exon 1-23del (3 families); Exon 14-20del (2 families) and E143X (2
      families). Six mutations in BRCA 2 were identified in 15 patients (12 families)
      including 8525delC (n = 2 families) and 8205-1G>C (n = 3 families). Patients with
      positive results had significantly higher Manchester scores than those with
      negative tests [median 25.5 (12-48) vs. 20 (8-37), p = 0.042, Mann-Whitney U
      test]. CONCLUSION: To identify patients with highly penetrant variants, referrals
      should be made with strict adherence to guidelines. Counselling should be
      individualised to counteract intrinsic psychological barriers to testing.

PMID- 23884709
TI  - Synthesis of silver nanoparticles using haloarchaeal isolate Halococcus
      salifodinae BK3.
AB  - Numerous bacteria, fungi, yeasts and viruses have been exploited for biosynthesis
      of highly structured metal sulfide and metallic nanoparticles. Haloarchaea (salt
      loving archaea) of the third domain of life Archaea, on the other hand have not
      yet been explored for nanoparticle synthesis. In this study, we report the
      intracellular synthesis of stable, mostly spherical silver nanoparticles (AgNPs)
      by the haloarchaeal isolate Halococcus salifodinae BK3. The culture on adaptation
      to silver nitrate exhibited growth kinetics similar to that of the control. NADH
      dependent nitrate reductase was involved in silver tolerance, reduction,
      synthesis of AgNPs, and exhibited metal-dependent increase in enzyme activity.
      The AgNPs preparation was characterized using UV-visible spectroscopy, XRD, TEM
      and EDAX. The XRD analysis of the nanoparticles showed the characteristic Bragg
      peaks of face-centered cubic silver with crystallite domain size of 22 and 12 nm
      for AgNPs synthesized in NTYE and halophilic nitrate broth (HNB), respectively.
      The average particle size obtained from TEM analysis was 50.3 and 12 nm for AgNPs
      synthesized in NTYE and HNB, respectively. This is the first report on the
      synthesis of silver nanoparticles by haloarchaea.

PMID- 23884710
TI  - Acidocella aromatica sp. nov.: an acidophilic heterotrophic alphaproteobacterium
      with unusual phenotypic traits.
AB  - Three obligately heterotrophic bacterial isolates were identified as strains of a
      proposed novel species of extremely acidophilic, mesophilic Alphaproteobacteria,
      Acidocella aromatica. They utilized a restricted range of organic substrates,
      which included fructose (but none of the other monosaccharides tested), acetate
      and several aromatic compounds (benzoate, benzyl alcohol and phenol). No growth
      was obtained on complex organic substrates, such as yeast extract and tryptone.
      Tolerance of the proposed type strain of the species (PFBC) to acetic acid was
      much greater than that typically reported for acidophiles. The bacteria grew
      aerobically, and catalyzed the dissimilatory reductive dissolution of the ferric
      iron mineral schwertmannite under both micro-aerobic and anaerobic conditions.
      Strain PFBC did not grow anaerobically via ferric iron respiration, though it has
      been reported to grow in co-culture with acid-tolerant sulfidogenic bacteria
      under strictly anoxic conditions. Tolerance of strains of Acidocella aromatica to
      nickel were about two orders of magnitude greater than those of other Acidocella
      spp., though similar levels of tolerance to other metals tested was observed. The
      use of this novel acidophile in solid media designed to promote the isolation and
      growth of other (aerobic and anaerobic) acidophilic heterotrophs is discussed.

PMID- 23884711
TI  - Characterization of hyperkalemic periodic paralysis: a survey of genetically
      diagnosed individuals.
AB  - This exploratory study aims to create an evidence-based comprehensive
      characterization of hyperkalemic periodic paralysis (hyperPP). HyperPP is a rare
      genetic disorder that causes episodes of flaccid paralysis. Disease descriptions
      in the literature are based upon isolated clinical encounters and case reports.
      We describe the experience of a large cohort of genetically diagnosed individuals
      with hyperPP. We surveyed genetically characterized individuals age 18 and over
      to assess disease comorbidities, diagnostic testing, management, and quality of
      life issues relevant to hyperPP. Myotonia was reported by 55.8 % of subjects and
      paramyotonia by 45.3 %. There is a relative risk of 3.6 (p < 0.0001) for thyroid
      dysfunction compared to the general population. Twenty-five percent of subjects
      experienced their sentinel attack in the second decade of life. It took an
      average of 19.4 years and visits to four physicians to arrive at the diagnosis of
      hyperPP. In addition to limbs and hands being affected during attacks, 26.1 % of
      subjects reported their breathing musculature was affected and 62.0 % reported
      their facial muscles were affected. There was a lifelong trend of increasing
      attack frequency, which was particularly common during childhood and adolescence.
      Approximately one-third of individuals experienced progressive myopathy.
      Permanent muscle weakness was evident and worsened during childhood and after age
      40. Those with no chronic treatment regimen have a RR of 2.3 for inadequate
      disease control compared to those taking long-term medications. This study
      revealed a multitude of heretofore unidentified characteristics of hyperPP, in
      addition to providing a different perspective on some previously held notions
      regarding the condition.

PMID- 23884713
TI  - Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia
      telangiectasia.
AB  - Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with
      prominent eye movement deficits localizing to the cerebellum. We sought to
      determine if 4-aminopyridine (4-AP), which putatively enhances the precision of
      Purkinje neurons, could improve the disorders of eye movements and vestibular
      function in A-T. The influence of 4-AP on disorders of eye movements and
      vestibular function was studied in four A-T patients. The effects on the
      cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed
      by the decay time constant of per- and post-rotational nystagmus during constant
      velocity en bloc rotations. The length of the VOR time constant determines the
      fidelity of the vestibular velocity storage, a neural mechanism that increases
      the bandwidth of VOR under cerebellar control. The VOR time constant was not
      increased in A-T patients. The latter is explained by the extent of cerebellar
      lesion as previously described in A-T and other cerebellar disorders.
      Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations.
      Severe disinhibition of velocity storage in subjects with putatively profound
      cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two
      A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the
      more severely affected individual and abrogated the PAN in the other. Two A-T
      subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary
      gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T
      4-AP has a prominent effect on the ocular motor and vestibular deficits that are
      ascribed to the loss of cerebellar Purkinje neurons. 

PMID- 23884714
TI  - Successful pallidal deep brain stimulation in 15-year-old with Tourette syndrome:
      2-year follow-up.

PMID- 23884716
TI  - Exploring the diversity of conceptualizations of work (dis)ability: a scoping
      review of published definitions.
AB  - PURPOSE: Researchers are confronted to numerous definitions of work
      ability/disability, influenced by their context of emergence, discipline,
      purpose, underlying paradigm and relationship to time. This study provides an in
      depth analysis of the concept through a systematic scoping review and the
      development of an integrative concept map of work (dis)ability. The research
      questions are: How has work (dis)ability been conceptualized from the
      perspectives of research, practice, policy and industry in the published
      scientific literature? How has the conceptualization of work (dis)ability evolved
      over time? METHODS: A search strategy was designed with a library scientist to
      retrieve scientific publications containing explicit definition(s) of work
      (dis)ability in leading-edge databases. The screening and the extraction of the
      definitions were achieved by duplicate assessment. The definitions were subject
      to a comparative analysis based on the grounded theory approach. RESULTS: In
      total, 423 abstracts were retrieved from the bibliographic databases. After
      removing duplicates, 280 unique records were screened for inclusion. A final set
      of 115 publications containing unique original conceptual definitions served as
      basis for analysis. CONCLUSIONS: The scientific literature does not reflect a
      shared, integrated vision of the exact nature and dimensions of work
      (dis)ability. However, except for a few definitions, there seems to be a
      consensus that work (dis)ability is a relational concept resulting from the
      interaction of multiple dimensions that influence each other through different
      ecological levels. The conceptualization of work (dis)ability also seems to have
      become more dynamic over time. The way work (dis)ability is defined has important
      implications for research, compensation and rehabilitation.

PMID- 23884717
TI  - A multicenter assessment of 1,177 cases of shoulder dystocia: lessons learned.
AB  - The purposes of this review were to describe deliveries complicated by shoulder
      dystocia (SD) at three tertiary centers and discern the differences between SD
      with and without brachial plexus injury (BPI). The inclusion criteria for this
      multicenter, retrospective study were singletons, delivered vaginally with SD. To
      discern the risk factors for SD with and without injury, a case (SD and BPI)
      versus control (3 SD without injury at the same institution) design was used.
      Multiple linear regression was employed. Over a 7-year period, among 46,637
      vaginal deliveries, SD occurred in 1,177 cases (2.5%) and BPI was noted in 11%.
      The results of multiple regression indicate that gestational age, operative
      delivery, and the number of maneuvers and concomitant fracture (4%) were
      statistically associated with BPI following SD (p < 0.001). SD was not associated
      with BPI in 89% and 88% of the cases that were resolved with McRoberts maneuver
      and suprapubic pressure, whereas only 0.2% of cases were litigated.

PMID- 23884715
TI  - Community composition of nirS-type denitrifier in a shallow eutrophic lake.
AB  - Denitrification is a major biological process to reduce nitrate to molecular
      nitrogen (N2). In shallow eutrophic lakes, this process can remove the largest
      portion of fixed nitrogen and plays an important role in self-purification of
      this ecosystem. To understand the structure of denitrifying communities in a
      shallow eutrophic lake, denitrifier communities in four sub-lakes of East Lake in
      Wuhan, China, were explored by restriction fragment length polymorphisms (RFLP)
      analysis and sequencing of nirS gene clone libraries. nirS is a functional marker
      gene for denitrification encoding cytochrome cd 1-containing nitrite reductase,
      which catalyzes the reduction of nitrite to nitric oxide. Both RFLP fingerprints
      clustering analysis and phylogeny analysis based on the amino acid sequences of
      NirS revealed that NirS-type communities in East Lake sediment could be roughly
      divided into three clusters. Cluster I accounted for 74-82 % of clones from the
      moderately eutrophic sub-lakes Tuan, Tang Ling, and Guo Zheng. Cluster II
      accounted for 76 % of the communities in hypertrophic sub-lake Miao Lake and
      cluster III as a minor group (7 % of the total), mainly presented in Miao Lake.
      Phylogenetic analysis revealed that cluster I was related to the reference clones
      from a broad range of ecological environments, and clusters II and III were more
      phylogenetically related to the reference clones from entrophic environments.
      Canonical correspondence analysis indicated that total nitrogen, total phosphate,
      total organic carbon, and NH4-N and NO2-N were important environmental factors
      affecting the dispersion of NirS-type denitrifier in the sediments. Cluster I
      showed a weak relationship with the nutrient content, while cluster II and III
      were positively related with the nutrient content. Principal coordinates analysis
      indicated that NirS-type communities from Tuan Lake, Tang Ling Lake, and Guo
      Zheng Lake sediments were divergent from those found in river, estuary sediment,
      and forest soil but similar to communities in constructed wetland sediment
      despite large geographic distances. The communities from the hypertrophic sub
      lake Miao Lake deviated from other sub-lakes and the reference communities and
      clustered independently. Our results support the argument that environmental
      factors regulate the composition and distribution of the functional bacterial
      groups. 

PMID- 23884718
TI  - Effect of hydration on spontaneous labor outcomes in nulliparous pregnant women:
      a multicenter randomized controlled trial comparing three methods.
AB  - OBJECTIVE: To evaluate the effect of mode and amount of fluid hydration during
      labor. STUDY DESIGN: The authors conducted a randomized controlled trial of
      uncomplicated nulliparous women in spontaneous labor at 36 weeks or more
      gestational age. Women were randomized to receive lactated Ringer solution with
      5% dextrose at (1) 125 mL/h intravenously with limited oral intake, (2) 250 mL/h
      intravenously with limited oral intake, or (3) 25 mL/h intravenously with ad
      libitum oral intake of clear liquids. Results were analyzed by intent-to-treat
      analysis. RESULTS: A total of 311 out of 324 women were available for analysis.
      Groups 1 (n = 105), 2 (n = 105), and 3 (n = 101) above did not differ
      significantly for mean labor duration (11.6 +/- 5.9, 11.4 +/- 5.5, and 11.5 +/-
      5.9 hours, respectively; p = 0.998), proportion of women in labor > 12 hours (all
      groups 41%; p = 0.998), proportion receiving oxytocin augmentation (59, 60, and
      57%, respectively; p = 0.923), or proportion delivered by cesarean (22, 17, and
      17%, respectively; p = 0.309). Indications for cesarean were similar between
      groups. No cases of pulmonary edema, maternal aspiration, or perinatal mortality
      occurred. CONCLUSION: Although apparently safe, neither increased intravenous
      hydration nor oral hydration during labor improves labor performance.

PMID- 23884719
TI  - Neurodevelopmental outcomes of very low birth weight preterm infants treated with
      poractant alfa versus beractant for respiratory distress syndrome.
AB  - BACKGROUND: Some controlled trials have shown significant differences in short
      term clinical outcomes between poractant alfa and beractant in infants with
      respiratory distress syndrome (RDS). There is, however, no study showing the
      differences in long-term outcomes with these treatments. AIM: To determine and
      compare the neurodevelopmental outcomes of preterm infants with RDS treated with
      poractant alfa or beractant at 2 years of age. METHODS: This was a prospective,
      longitudinal, single-center cohort study of infants born at <= 1,500 g and/or <=
      32 weeks between 2008 and 2009 who received either poractant alfa (n = 113) or
      beractant (n = 102) for RDS. Neurological and developmental assessments were
      performed at a corrected age of 18 to 24 months. RESULTS: About 33 of 113 infants
      (29.2%) in the poractant alfa group had neurodevelopmental impairment compared
      with 36 of 102 (35.2%) in the beractant group, and the results did not differ
      between the groups (p = 0.339). Similarly, no significant difference was found in
      the percentage of infants with cerebral palsy (11.5 vs. 16.7%, respectively; p =
      0.275). CONCLUSION: Our findings suggest that poractant alfa and beractant are
      similar in terms of neurodevelopmental outcomes when used for the treatment of
      RDS in preterm infants.

PMID- 23884720
TI  - Endogenous synthesis of prostacyclin was positively regulated during the
      maturation phase of cultured adipocytes.
AB  - Prostacyclin alternatively called prostaglandin (PG) I2 is an unstable metabolite
      synthesized by the arachidonate cyclooxygenase pathway. Earlier studies have
      suggested that prostacyclin analogues can act as a potent effector of adipose
      differentiation. However, biosynthesis of PGI2 has not been determined
      comprehensively at different life stages of adipocytes. PGI2 is rapidly
      hydrolyzed to the stable product, 6-keto-PGF1alpha, in biological fluids.
      Therefore, the generation of PGI2 can be quantified as the amount of 6-keto
      PGF1alpha. In this study, we attempted to develop a solid-phase enzyme-linked
      immunosorbent assay (ELISA) using a mouse antiserum specific for 6-keto
      PGF1alpha. According to the typical calibration curve of our ELISA, 6-keto
      PGF1alpha can be quantified from 0.8 pg to 7.7 ng in an assay. The evaluation of
      our ELISA revealed the higher specificity of our antiserum without the cross
      reaction with other related prostanoids while it exhibited only the cross
      reaction of 1.5 % with PGF2alpha. The resulting ELISA was applied to the
      quantification of 6-keto-PGF1alpha generated endogenously by cultured 3T3-L1
      cells at different stages. The cultured cells showed the highest capability to
      generate 6-keto-PGF1alpha during the maturation phase of 4-6 days, which was
      consistent with the coordinated changes in the gene expression of PGI synthase
      and the IP receptor for PGI2. Following these events, the accumulation of fats
      was continuously promoted up to 14 days. Thus, our immunological assay specific
      for 6-keto-PGF1alpha is useful for monitoring the endogenous levels of the
      unstable parent PGI2 at different life stages of adipogenesis and for further
      studies on the potential association with the up-regulation of adipogenesis in
      cultured adipocytes. 

PMID- 23884721
TI  - Immunomodulatory effects of IL-12 released from poly-N-acetyl glucosamine gel
      matrix during schistosomiasis infection.
AB  - We have reported recently that Interleukin-12 (IL-12) released from poly-N-acetyl
      glucosamine gel matrix (F2 gel/IL-12) is more effective than free IL-12 to
      enhance vaccination of mice with Schistosoma soluble worm antigen preparation.
      The aim of this study is to evaluate the effect of F2 gel/IL-12 on the
      inflammatory responses in mice undergoing schistosomiasis infection in absence of
      vaccination. To achieve this, mice undergoing Schistosoma mansoni infection or
      cured from this infection, after treatment with praziquantil (PZQ), were treated
      with subcutaneous injection of IL-12 for 3 consecutive days or once with F2 gel
      loaded with IL-12 (F2 gel/IL-12). The treatment was started on day 35 days after
      infection. For infection, mice were infected with 100 cercariae of S. mansoni
      using tail immersion method. We found that treatment with F2 gel/IL-12 induced
      significant decreases in the egg burden with a moderate reduction in the size of
      granuloma and decrease in the cellular granulomatous reaction in the lung as
      compared to infected mice treated with IL-12. These effects of F2 gel/IL-12 were
      more pronounced in infected mice previously treated with the anti-schistosomal
      drug PZQ. The total numbers of white blood cells in all treated mice showed
      similar profile. Treatment with IL-12 or F2 gel/IL-12, however, showed
      significant reduction in the number of mononuclear cells when compared with non
      treated infected mice. In conclusion, this study showed the ability of IL-12
      released from F2 gel to lower the inflammatory response to Schistosoma infection
      even in absence of vaccination. 

PMID- 23884722
TI  - The variegate neurological manifestations of varicella zoster virus infection.
AB  - Varicella zoster virus (VZV) is an exclusively human neurotropic
      alphaherpesvirus. Primary infection causes varicella (chickenpox), after which
      the virus becomes latent in ganglionic neurons along the entire neuraxis. With
      advancing age or immunosuppression, cell-mediated immunity to VZV declines, and
      the virus reactivates to cause zoster (shingles), dermatomal distribution, pain,
      and rash. Zoster is often followed by chronic pain (postherpetic neuralgia),
      cranial nerve palsies, zoster paresis, vasculopathy, meningoencephalitis, and
      multiple ocular disorders. This review covers clinical, laboratory, and
      pathological features of neurological complications of VZV reactivation,
      including diagnostic testing to verify active VZV infection in the nervous
      system. Additional perspectives are provided by discussions of VZV latency,
      animal models to study varicella pathogenesis and immunity, and of the value of
      vaccination of elderly individuals to boost cell-mediated immunity to VZV and
      prevent VZV reactivation. 

PMID- 23884723
TI  - Daptomycin underexposure in a young intravenous drug user who was affected by
      life-threatening Staphylococcus aureus-complicated skin and soft tissue infection
      associated with bacteraemia.
AB  - We describe the case of an intravenous drug user affected by life-threatening
      Staphylococcus aureus-complicated skin and soft tissue infection with associated
      bacteraemia who, while on replacement therapy with methadone, required 11
      mg/kg/day daptomycin to achieve trough (Cmin) and peak (Cmax) plasma levels
      similar to those observed with the standard dosage of 6 mg/kg in healthy
      volunteers (mean +/- standard deviation: Cmin 12.35 +/- 0.80 mg/L, Cmax 63.90 +/-
      8.71 mg/L). Clinical pharmacological advice based on real time therapeutic drug
      monitoring may be helpful for optimizing daptomycin exposure in these patients.
      Physicians should take into account that dosages much higher than the standard
      ones may be needed, probably as a consequence of augmented drug clearance.

PMID- 23884725
TI  - Unknown complication of preputial calculi: preputial skin fistula.

PMID- 23884726
TI  - Assessment of glomerular filtration rate in elderly patients with chronic kidney
      disease.
AB  - PURPOSE: We sought to evaluate various glomerular filtration rate (GFR)
      estimating equations in elderly patients with chronic kidney disease (CKD).
      METHODS: A total of 332 Chinese elderly patients with CKD who had undergone
      technetium-99m diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) renal dynamic
      imaging were enrolled. The MDRD equation, the re-expressed MDRD equation, the
      Chinese equation, the Ruijin equation, the previously Japanese equation, the new
      Japanese equation, the CKD-EPI equation, and the BIS1 equation were compared.
      RESULTS: The median of difference between estimated GFR and standard GFR ranged
      from -9.78 to 1.79 ml/min/1.73 m(2). The interquartile range of difference ranged
      from 12.38 to 20.87 ml/min/1.73 m(2). Accuracy with a deviation <30 % ranged from
      44.9 to 66.3 %. However, none of the equations had accuracy up to the 70 % level.
      Bland-Altman analysis demonstrated that the precision ranged from 50.5-87.6
      ml/min/1.73 m(2). The slopes of regression line ranged from -0.26 to 0.55 and the
      intercepts ranged from -18.71 to 11.07. In both the overall performance and the
      performances in different stage of CKD, GFR estimated by the BIS1 equation
      performed better results. CONCLUSION: None of the GFR estimating equations are
      suitable for the specific Chinese population tested. At present, the BIS1
      equation may be the optimal one for elderly Chinese CKD patients.

PMID- 23884727
TI  - Lung ultrasound during hemodialysis: the role in the assessment of volume status.
AB  - OBJECTIVE: Fluid balance is important in patients undergoing hemodialysis. "Dry"
      weight is usually estimated clinically, and also, bioimpedance is considered
      reliable. Ultrasonography of inferior vena cava (IVC) estimates central venous
      pressure, and lung ultrasound evaluates extravascular (counting B-lines artifact)
      lung water. Our study was aimed to clarify their usefulness in the assessment of
      volume status during hemodialysis. METHODS: A total of 71 consecutive patients
      undergoing hemodialysis underwent lung and IVC ultrasound and bioimpedance
      spectroscopy immediately before and after dialysis. RESULTS: There was a
      significant reduction in the number of B-lines (3.13 vs 1.41) and in IVC
      diameters (end-expiratory diameter 1.71 vs 1.37; end-inspiratory diameter 1.19 vs
      0.95) during dialysis. The reduction in B-lines correlated with weight reduction
      during dialysis (p 0.007); none of the parameters concerning the IVC correlated
      with fluid removal. At the end of the dialysis session, the total number of B
      lines correlated with bioimpedance residual weight (p 0.002). DISCUSSION: The
      reduction in B-lines correlated with fluid loss due to hemodialysis, despite the
      small pre-dialysis number, confirming that lung ultrasound can identify even
      modest variations in extravascular lung water. IVC ultrasound, which reflects the
      intravascular filling grade, might not be sensitive enough to detect rapid volume
      decrease. Clinically estimated dry weight had a poor correlation with both
      bioimpedance and ultrasound techniques. Post-dialysis B-lines number correlates
      with residual weight assessed with bioimpedance, suggesting a role for ultrasound
      in managing hemodialysis patients.

PMID- 23884728
TI  - Lymph node dissection during radical cystectomy for bladder cancer treatment:
      considerations on relevance and extent.
AB  - Despite advances in the surgical and medical treatment for urothelial carcinoma
      of the bladder (UCB), there have only been limited improvements in disease
      specific mortality rates over the past decades. Lymph node dissection (LND)
      during radical cystectomy is an integral part of the treatment for muscle
      invasive and high-risk UCB. LND may detect and remove lymph node (LN) metastasis
      and thus guide patient counseling and decision making regarding additional
      treatment decisions. In addition, LND may improve survival in patients both with
      and without LN metastasis. In this non-systematic review article, we discuss
      benefits and risks of LND, the role of limited versus extended LND and the
      dilemma of preoperative LN staging. 

PMID- 23884729
TI  - Ultrasonographic evaluation of peritoneal membrane thickness and comparison with
      the effectiveness and duration of CAPD.
AB  - BACKGROUND: The few studies on the morphology and functions of CAPD and
      peritoneum have tended to use histological and histomorphometrical methods.
      However, such methods are known to require biopsy, which is an invasive method.
      The present study aims to determine the morphological changes established by
      ultrasonography in CAPD patients, as well as achieving a comparison between these
      changes and the functional properties of peritoneum in CAPD. We aim to determine
      the effects of the duration of CAPD upon peritoneal thickness. METHODS: The study
      included 42 CAPD patients. Twenty-four of them had peritoneal dialysis (PD)
      duration of less than 24 months (Group 1) and 18 of them had PD duration of
      longer than 48 months (Group 2). Patients with a history of surgery involving the
      peritoneum and abdomen and with a history of peritonitis in the last 3 months
      were excluded. We examined the parietal peritoneum by trans-abdominal
      ultrasonography. RESULTS: There was a statistically significant positive
      correlation between PD duration and peritoneal thickness of each quadrant. There
      was a statistically significant negative correlation between membrane thickness
      and creatinine clearance (CrCl), peritoneal Kt/V (pKt/V) and normalized protein
      catabolic rate. There was a positive significant correlation between membrane
      thickness and dialysate/plasma creatinine ratio. There was a statistically
      significant difference between the two groups according to their peritoneal
      membrane thickness. CrCl and pKt/V values were better in Group 1 than in Group 2.
      CONCLUSION: Our study revealed that increased PD duration may have a relation
      with increased peritoneal membrane thickness, and this can be associated with
      less effective PD. Ultrasound imaging has an important role for evaluating
      peritoneal membrane thickness without using an invasive method such as biopsy and
      can be performed easily in dialysis clinics.

PMID- 23884730
TI  - How to manage total avulsion of the ureter from both ends: our experience and
      literature review.
AB  - OBJECTIVES: To evaluate the treatment alternatives of total avulsion of the
      ureter from both ends including ureteropelvic junction (UPJ) and ureterovesical
      junction (UVJ). METHODS: Total ureteral avulsion on both ends of the ureter was
      examined in 4 cases performing ureteroscopy. In two male patients of the four
      cases, avulsion was noticed intraoperatively and ureteral re-anastomosis at UPJ
      and re-implantation at UVJ were performed immediately. Boari flap was performed
      for one female patient immediately and for the other female patient who was
      referred from another hospital after the ureteroscopy, 4 days later. RESULTS: One
      patient who had ureteral re-implantation was followed with 3-month intervals by
      ultrasonography and abdominal X-ray. At the end of 1 year, it was determined that
      kidney parenchyma was normal and the patient had kidney and upper ureteral
      stones. Percutaneous nephrolithotomy was performed, and the patient was stone
      free at the end of the operation. Two years after the surgery, both kidneys were
      normal. This is the only case who had a successful ureteral re-implantation in
      literature. The other patient turned up a year later for routine checks after the
      ureteral stent was removed. Then, hydronephrosis and renal atrophy were detected.
      The patient did not accept nephrectomy or any other intervention and he was lost
      to follow-up. Boari flap procedure was performed after UPJ repair for the other
      two female patients. Their kidneys were both normal 3 months after the operation.
      CONCLUSIONS: In case of ureteral avulsion from both ends of the ureter in the
      male patients, as bladder capacity is not enough for a Boari flap, proximal
      anastomosis and distal re-implantation could be a good choice for the management
      of this untoward event. This new approach also saves time for reconstructive
      treatments if necessary. If bladder capacity is enough to reach UPJ, Boari flap
      could be a good choice in female patients.

PMID- 23884731
TI  - Transformation of adult cerebellar pilocytic astrocytoma to glioblastoma.
AB  - A 54-year-old woman with a past history of uterine cancer developed a tumor in
      her right cerebellum. Magnetic resonance imaging with contrast enhancement
      revealed a mass composed of two components, inside and outside, although both
      components resided in the same high-intensity area on T2-weighted imaging.
      Surgical resection removed the bulk of the tumor. Pathological examination
      revealed two distinct pathological features of the tumor-the inner major
      component had the features of glioblastoma whereas outer minor component had
      those of pilocytic astrocytoma (PA). These two components occurred with
      intercalating transitional areas. No genetic differences, including BRAF
      alteration or IDH mutations, were detected in either component. Activation of
      Akt, which is reported to be associated with clinically aggressive and anaplastic
      PA was found in the PA component of this tumor. The transitional area also
      stained positive, suggesting the continuity of both components. Consequently, the
      glioblastoma in this case was likely to have developed as a result of malignant
      transformation of PA. This case provides additional support for the concept of
      anaplastic transformation of PA.

PMID- 23884732
TI  - Acute myeloid leukaemia with mutated NPM1 presenting with extensive bone marrow
      necrosis and Charcot-Leyden crystals.
AB  - Here, we report an unusual case of acute myeloid leukaemia with mutated NPM1
      presenting with pancytopenia and leukoerythroblastosis, without circulating
      blasts and bone marrow necrosis with numerous Charcot-Leyden crystals, but no
      eosinophilia. 

PMID- 23884733
TI  - Effects of isotonic and isometric exercises with mist sauna bathing on
      cardiovascular, thermoregulatory, and metabolic functions.
AB  - To clarify the effects of isometric and isotonic exercise during mist sauna
      bathing on the cardiovascular function, thermoregulatory function, and
      metabolism, six healthy young men (22 +/- 1 years old, height 173 +/- 4 cm,
      weight 65.0 +/- 5.0 kg) were exposed to a mist sauna for 10 min at a temperature
      of 40  degrees C, and relative humidity of 100 % while performing or not
      performing ~30 W of isometric or isotonic exercise. The effect of the exercise
      was assessed by measuring tympanic temperature, heart rate, systolic and
      diastolic blood pressure, chest sweat rate, chest skin blood flow, and plasma
      catecholamine and cortisol, glucose, lactate, and free fatty acid levels.
      Repeated measures ANOVA showed no significant differences in blood pressure, skin
      blood flow, sweat rate, and total amount of sweating. Tympanic temperature
      increased more during isotonic exercise, and heart rate increase was more marked
      during isotonic exercise. The changes in lactate indicated that fatigue was not
      very great during isometric exercise. The glucose level indicated greater energy
      expenditure during isometric exercise. The free fatty acid and catecholamine
      levels indicated that isometric exercise did not result in very great energy
      expenditure and stress, respectively. The results for isotonic exercise of a
      decrease in lactate level and an increase in plasma free fatty acid level
      indicated that fatigue and energy expenditure were rather large while the
      perceived stress was comparatively low. We concluded that isotonic exercise may
      be a more desirable form of exercise during mist sauna bathing given the changes
      in glucose and free fatty acid levels.

PMID- 23884735
TI  - [Key facts from new guidelines].

PMID- 23884734
TI  - Screening mammography recall rate: does practice site matter?
AB  - PURPOSE: To determine whether the screening mammography recall rate for
      individual radiologists varies as a function of imaging site. MATERIALS AND
      METHODS: Institutional review board-approved, HIPAA-compliant retrospective
      review of mammography audit data was performed between May 1, 2008, and September
      1, 2011, for five radiologists with expertise in breast imaging interpreting
      mammograms at a community office practice and an academic referral hospital.
      Informed consent was waived. Both sites used full-field digital mammography and
      batch screening interpretation. Recall rates were calculated from audit data.
      Breast density, history of surgery or biopsy, and availability of prior
      mammograms were compared in a sample of 500 mammograms from each site by using
      chi(2) and two-sample t tests. RESULTS: Radiologists interpreted a total of 74
      297 screening mammograms between both sites during the study. The overall mean
      recall rate was 7.8% +/- 0.2 (standard deviation). Overall recall rate at the
      community site was significantly lower than at the hospital site (6.9% +/- 0.3 vs
      8.6% +/- 0.3, P < .001). Recall rates for each radiologist were also lower at the
      community site: 3.7% versus 6.5% (P < .001), 9.6% versus 12.0% (P < .001), 7.5%
      versus 9.1% (P = .01), 7.6% versus 11.5% (P < .001), and 5.6% versus 8.0% (P =
      .02). There was a significantly higher proportion of patients at the hospital
      site with a history of surgery (13.4% vs 5.6%, P < .001) and biopsy (7.0% vs
      1.4%, P < .001) but no difference in the percentage with dense breasts or in the
      percentage with availability of prior mammograms. Mean patient age was lower at
      the hospital site: 56.1 versus 62.9 years (P < .001). CONCLUSION: Recall rates
      were higher at the hospital site, probably primarily caused by patient population
      factors.

PMID- 23884736
TI  - [Treatment of chronic systolic heart failure].

PMID- 23884737
TI  - [Pulmonary embolism: update 2013].

PMID- 23884738
TI  - [Skin and hormones: news from dermato-endocrinology].

PMID- 23884739
TI  - [The kidneys in the elderly].

PMID- 23884740
TI  - [Prosthetic joint infection: new developments in diagnosis and treatment].

PMID- 23884741
TI  - [Acute and acute-on chronic-liver failure].

PMID- 23884742
TI  - [Catheter ablation of ventricular tachycardia].
AB  - Since the last decade important advances in diagnostics, understanding and the
      ablation techniques of ventricular tachycardia (VT) have been made. Both,
      patients with idiopathic VT and patients with structural heart disease and scar
      related VT undergo VT ablation, that targets the underlying substrate responsible
      for VT development. Use of 3-dimensional electro-anatomic mapping systems enables
      identification of scar-related slow conduction sites, that are the critical
      players in scar-related VT. Successful mapping and ablation of mono- and
      polymorphic VT and ventricular fibrillation is achieved at specialized centers
      and is associated with reduced hospitalizations and mortality in patients with
      recurrent ICD shocks. This article describes the mechanisms of VTs, current
      mapping and ablation techniques and the results and complications of VT ablation
      at experienced VT ablation centers. 

PMID- 23884743
TI  - [Standards and perspectives in the treatment of lupus nephritis].

PMID- 23884744
TI  - [Lung transpantation].

PMID- 23884745
TI  - [Rheumatic diseases in pregnancy].

PMID- 23884746
TI  - [Diverticulosis and diverticular disease].

PMID- 23884747
TI  - [73-year-old patient with unusual chest X-ray].

PMID- 23884748
TI  - [Severe oral mucositis in a patient with HIV infection].
AB  - HISTORY AND CLINICAL FINDINGS: A 50-year-old man with HIV infection (first
      diagnosed > 20 years ago) presented at our hospital with fulminant oral
      mucositis. Antiretroviral therapy (tenofovir, emtricitabine, raltegravir) had
      been started 2 months ago. Previously he had no opportunistic infections and no
      other pre-existing illnesses. He had not travelled outside Europe but stayed in
      Spain for several weeks during summer. INVESTIGATIONS: Physical examination
      revealed swelling of the lips and severe ulcerative mucositis of the gums and
      pharynx. The patient complained of painful swallowing. The blood-chemistry showed
      no abnormalities. The microscopical analysis of a smear and a biopsy of the
      buccal mucosa revealed amastigotes of leishmania. By means of PCR technique,
      Leishmania donovani complex was specified. TREATMENT AND COURSE: The patient was
      treated with liposomal amphotericin B (1 mg/kg) for 21 days. Because of the
      immunosuppression he was put on maintenance therapy afterwards (liposomal
      amphotericin B every 3 weeks). However, 4 months later there was a clinical
      relapse of the mucositis and a new cultural and PCR detection of leishmania in a
      buccal biopsy. After another course of 21 days with liposomal amphotericin B (3
      mg/kg) and miltefosine (150 mg/d), the mucositis subsided. Therapy with liposomal
      amphotericin B (3 mg/kg single dose every 3 weeks) has since been maintained. The
      antiretroviral therapy was changed meanwhile to lamivudin, abacavir and
      raltegravir because of kidney failure with elevated urea and creatinine. The
      patient has been clinically stable ever since without any other HIV-related
      problems. The latest CD4 count was 456/ul and the HIV load 340 copies/ml.
      CONCLUSION: Leishmaniasis is a severe infection in HIV-positive patients.
      Clinical manifestations can be atypical in immunosuppressed patients and the
      treatment is complicated with HIV coinfection. This is also due to a lifelong
      persistence of the parasite with potential reactivation especially in patients
      with suppressed CD4 cells. Therefore maintenance therapy after standard therapy
      of leishmaniasis is mandatory at least for a CD4 count below 350/ul. Especially
      in HIV patients with a leishmaniasis relapse lifelong maintenance therapy should
      be considered.

PMID- 23884749
TI  - [Prioritisation in medical care - or: how can medicine hold its ground?].

PMID- 23884750
TI  - Resection of hepatocellular carcinoma with macroscopic vascular invasion.
AB  - BACKGROUND: Survival for Child's A patients with hepatocellular cancer (HCC) and
      macroscopic vascular invasion (MVI) has been reported as approximately 8.1 months
      with sorafenib. The role of surgery for these patients remains controversial.
      METHODS: The records of all patients undergoing resection of HCC at a single
      center were reviewed. Only patients with pathologically proven MVI were included.
      Inclusion criteria for resection required Child's A liver disease, no clinical
      portal hypertension (after 2002), and no extrahepatic disease. The superior
      mesenteric vein and portal vein branch to the remaining lobe had to be patent.
      RESULTS: We identified 165 patients with MVI treated with hepatic resection
      between June 1992 and March 2010. Median follow-up was 11.9 months with 127
      deaths, including 12 (7.3%) perioperative mortalities. Median and 5-year
      survivals were 13.1 months and 14%. Multivariate analysis found alpha-fetoprotein
      (AFP) >30 ng/ml (hazard ratio 2.07), tumor size >7 cm (hazard ratio 1.59), and
      extent of vascular invasion (hazard ratio 1.74) to be independently associated
      with survival. Those with invasion of hepatic veins or vena cava had a median
      survival of only 4.7 months. CONCLUSIONS: The results for resection of HCC with
      MVI remain somewhat disappointing but are better than what is reported with
      medical therapy in similar patients. Tumor size, AFP, and extent of vascular
      invasion can help select those that will benefit most from hepatic resection.
      Resection of patients with hepatic vein or vena cava involvement may not be
      justified, given such poor results.

PMID- 23884751
TI  - Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are
      prognostic factors in different cohorts of patients undergoing breast, lung, and
      kidney cancer surgery.
AB  - BACKGROUND: Inflammation is associated with a worse outcome in cancer and
      neutrophil:lymphocyte ratio (NLR) is a strong prognostic value. In cancer,
      nonsteroidal anti-inflammatory drugs (NSAIDs) could be of interest. We
      investigated the prognostic significance of NLR and the impact of intraoperative
      NSAIDs in cancer surgeries. METHODS: We performed an observational study in early
      breast, kidney, and lung cancers (357, 227, and 255 patients) with uni- and
      multivariate analyses (Cox model). RESULTS: In breast cancer (Centre 1), NLR >= 4
      is associated with a higher risk of relapse (hazards ratio (HR) = 2.41; 95 %
      confidence interval (CI) 1.01-5.76; P = 0.048). In breast cancer (Centre 2), NLR
      >= 3 is associated with a higher risk of relapse (HR = 4.6; 95 % CI 1.09-19.1; P
      = 0.04) and higher mortality (HR = 4.0; 95 % CI 1.12-14.3; P = 0.03). In kidney
      cancer, NLR >= 5 is associated with a higher risk of relapse (HR = 1.63; 95 % CI
      1.00-2.66; P = 0.05) and higher mortality (HR = 1.67; 95 % CI 1.0-2.81; P =
      0.05). In lung cancer, NLR >= 5 is associated with higher mortality (HR = 1.45;
      95 % CI 1.02-2.06; P = 0.04). The intraoperative use of NSAIDs in breast cancer
      patients (Centre 1) is associated with a reduced recurrence rate (HR = 0.17; 95 %
      CI 0.04-0.43; P = 0.0002) and a lower mortality (HR = 0.25; 95 % CI 1.08-0.75; P
      = 0.01). NSAIDs use at the beginning of the surgery is independently associated
      with a lower metastases risk after lung cancer surgery (HR = 0.16; 95 % CI 0.04
      0.63; P = 0.009). Ketorolac use is independently associated with longer survival
      (HR = 0.55; 95 % CI 0.31-0.95; P = 0.03). CONCLUSIONS: In these cohorts, these
      analyses show that NLR is a strong perioperative prognosis factor for breast,
      lung, and kidney cancers. In this context, intraoperative NSAIDs administration
      could be associated with a better outcome.

PMID- 23884752
TI  - MicroRNA from pancreatic duct aspirate differentiates cystic lesions of the
      pancreas.
AB  - INTRODUCTION: Prognostication for cystic neoplasms of the pancreas continues to
      evolve. Beyond simple size and cystic fluid CEA determination, microRNA (miRNA)
      detection holds great promise as molecular diagnostics for cancer risk. In this
      study, we sought to identify miRNAs that could predict malignant potential of
      pancreatic cystic lesions. METHODS: RNA was harvested from the pancreatic duct
      aspirate of 72 cystic neoplasms of the pancreas. Samples with adequate RNA
      concentration (>= 3 ng/MUL) were selected for qRTPCR profiling using assays to
      379 of the most common miRNAs. miRNA profiles were correlated with histopathology
      from resected specimens and grouped by benign (serous cystadenomas), premalignant
      (intraductal papillary mucinous neoplasms and mucinous cystadenomas), or
      malignant lesions (adenocarcinoma). RESULTS: Adequate RNA for analysis was
      obtained from 42 (58.3 %) of the samples. Malignant lesions were more likely to
      have adequate RNA (n = 17, 81 %) than either benign (n = 6, 33 %) or premalignant
      lesions (n = 19, 59 %; p = 0.011). Nine miRNA were identified as differentially
      expressed between benign and premalignant/malignant lesions (p < 0.05). A
      significant correlation was found between the number of differentially expressed
      miRNA and the likelihood of a premalignant/malignant lesion. All premalignant or
      malignant lesions expressed at least one miRNA surpassing the threshold of mean
      miRNA expression, whereas no benign lesions had more than one miRNA surpassing
      the threshold. CONCLUSIONS: The presence of RNA in the duct aspirate from
      patients with pancreatic cystic neoplasms may be a predictor of premalignancy or
      malignancy. miRNA may be utilized to further differentiate between benign,
      premalignant, and malignant cystic lesions of the pancreas.

PMID- 23884753
TI  - Discriminating pheochromocytomas from other adrenal lesions: the dilemma of
      elevated catecholamines.
AB  - BACKGROUND: Screening tests for pheochromocytoma involve measuring levels of
      catecholamines in the urine or plasma, which have significant false-positive
      rates. We reviewed patients with adrenal masses and elevated levels of
      catecholamines to determine the value of different preoperative tests in
      diagnosing pheochromocytomas. METHODS: A retrospective chart review identified
      patients who underwent adrenalectomy between 1997 and 2011 with elevation of
      urine or serum catecholamines. A database of clinicopathologic factors was
      created including preoperative urine and plasma metanephrines, normetanephrines,
      vanillylmandelic acid, and fractionated catecholamines, and tumor dimensions on
      imaging and pathology. RESULTS: A total of 70 patients underwent adrenalectomy
      because of presence of an adrenal mass and elevation of catecholamines or
      normetanephrines or metanephrines. Of these, 46 had pathologically confirmed
      pheochromocytomas. To improve our ability to discriminate between
      pheochromocytoma and other pathology, we examined different combinations of
      clinicopathologic factors and catecholamine levels and found the best test was a
      scoring system. Points are awarded for a hierarchy of elevated normetanephrine,
      norepinephrine, metanephrines, with additional points received for age <50 and
      size on imaging >3.3 cm. A score of 2 is suggestive of pheochromocytoma, with a
      positive predictive value of 86-87%, while a score of 4 is diagnostic with
      positive predictive value of 100%. CONCLUSION: We found that urine/serum
      normetanephrine levels were the most valuable screening tool; however, a score
      examining the size of adrenal mass on preoperative CT, age, and either plasma or
      urine norepinephrine, metanephrine, and normetanephrine values leads to a higher
      positive predictive value, making this scoring system superior to individual lab
      tests.

PMID- 23884754
TI  - Discordance between conventional and detailed lymph node analysis in resected
      biliary carcinoma at or above the cystic duct: are we understaging patients?
AB  - BACKGROUND: Analysis of portal lymph node (LN) metastases following resection of
      biliary carcinomas at or above the cystic duct (BC) is used to select patients
      for adjuvant therapy, but no guidelines exist and LN yield is low. Some consider
      analysis of 7 LNs necessary for accurate staging. Conventional LN analysis may
      understage patients. METHODS: Portal LNs from 38 node-negative patients following
      resection of BC from 2000 to 2008 were re-examined in detail for occult
      metastases (OM) using a modified Weaver protocol. Outcomes measured were
      discordance in LN positivity and patient survival. RESULTS: On detailed
      examination, 5 of 38 patients had OM. There was no difference in survival between
      patients with and without OM (24 vs 17 months; p = .382). There was no
      association between OM and patient demographics or adverse tumor characteristics.
      The median LN yield was 3. Of the 27 patients with <7 LNs retrieved, 1 had OM,
      compared with 4 of 11 patients with >=7 LNs retrieved (p = .030). OM in these
      well-staged patients were associated with reduced survival (9 vs 41 months; p =
      .032). CONCLUSIONS: There is discordance between conventional and detailed LN
      analysis in resected BC. LN yield >=7 was associated with OM. The presence of OM
      may be associated with decreased survival. Conventional LN analysis may
      understage patients with resected BC.

PMID- 23884755
TI  - Polypharmacy of osteoarthritis: the perfect intestinal storm.
AB  - Osteoarthritis is an increasingly prevalent disorder with an incidence rate that
      rises sharply with age. Unfortunately, the most commonly used medications for
      providing symptomatic relief, nonsteroidal anti-inflammatory drugs (NSAIDs), can
      cause significant gastrointestinal (GI) ulceration. There is recent evidence that
      agents commonly employed to protect the upper GI tract actually increase the
      incidence and severity of ulceration and bleeding in the lower intestine.
      Intestinal injury is more difficult to diagnose and treat than upper GI damage,
      and symptoms correlate poorly with the severity of tissue injury. Moreover, use
      of low-dose aspirin for cardioprotection (a common co-treatment with the
      selective cyclooxygenase-2 inhibitors) further augments intestinal damage,
      particularly when enteric-coated aspirin is used. Thus, by focusing entirely on
      prevention of NSAID-induced damage to the upper GI tract, physicians may be
      inadvertently placing their patients at risk of serious, difficult-to-diagnose
      injury for which there are no proven-effective therapies and are associated with
      significantly higher rates of morbidity and mortality. 

PMID- 23884756
TI  - Treatment of nonampullary sporadic duodenal adenomas with endoscopic mucosal
      resection or ablation.

PMID- 23884757
TI  - Is liver-specific gadoxetic acid-enhanced magnetic resonance imaging a reliable
      tool for detection of hepatocellular carcinoma in patients with chronic liver
      disease?
AB  - BACKGROUND: Gadoxetic acid is a recently developed hepatobiliary-specific
      contrast material used for magnetic resonance imaging (MRI) which enables highly
      sensitive detection of hepatocellular carcinoma (HCC). AIM: We performed a meta
      analysis of all available studies of the diagnostic performance of gadoxetic acid
      enhanced MRI (Gd-EOB-MRI) for detection of HCC in patients with chronic liver
      disease. METHODS: Databases including MEDLINE and EMBASE were searched for
      relevant original articles published from January 2000 to April 2012. Pooled
      estimation and subgroup analysis data were obtained by statistical analysis.
      RESULTS: Across 10 studies of 570 patients, Gd-EOB-MRI sensitivity was 0.91 (95 %
      CI 0.77, 0.97) and specificity was 0.93 (95 % CI 0.85, 0.97). Overall, LR+ was
      13.6 (95 % CI 5.6, 33.2), LR- was 0.10 (95 % CI 0.04, 0.27), and DOR was 140.36
      (95 % CI 28, 696). Among patients with high pre-test probabilities, MRI enabled
      confirmation of HCC; among patients with low pre-test probabilities, MRI enabled
      exclusion of HCC. Worst-case-scenario (pre-test probability, 50 %) post-test
      probabilities were 93 and 9 % for positive and negative MRI results,
      respectively. In studies in which both Gd-EOB-MRI and contrast enhanced computed
      tomography (CE-CT) were performed, Gd-EOB-MRI was more sensitive than CE-CT (0.93
      vs. 0.78; p < 0.05). Subgroup analysis suggested average lesion size (<2 vs. >2
      cm) did not affect the diagnostic accuracy of the test (p > 0.05). CONCLUSIONS: A
      limited number of small studies suggest Gd-EOB-MRI has good diagnostic
      performance in the detection of HCC among patients with chronic liver disease. It
      is also confirmed to be a reliable tool for evaluation of small early-stage HCC.

PMID- 23884758
TI  - Inter- and intrascanner variability of pulmonary nodule volumetry on low-dose 64
      row CT: an anthropomorphic phantom study.
AB  - OBJECTIVE: To assess inter- and intrascanner variability in volumetry of solid
      pulmonary nodules in an anthropomorphic thoracic phantom using low-dose CT.
      METHODS: Five spherical solid artificial nodules [diameters 3, 5, 8, 10 and 12
      mm; CT density +100 Hounsfield units (HU)] were randomly placed inside an
      anthropomorphic thoracic phantom in different combinations. The phantom was
      examined on two 64-row multidetector CT (64-MDCT) systems (CT-A and CT-B) from
      different vendors with a low-dose protocol. Each CT examination was performed
      three times. The CT examinations were evaluated twice by independent blinded
      observers. Nodule volume was semi-automatically measured by dedicated software.
      Interscanner variability was evaluated by Bland-Altman analysis and expressed as
      95% confidence interval (CI) of relative differences. Intrascanner variability
      was expressed as 95% CI of relative variation from the mean. RESULTS: No
      significant difference in CT-derived volume was found between CT-A and CT-B,
      except for the 3-mm nodules (p<0.05). The 95% CI of interscanner variability was
      within +/-41.6%, +/-18.2% and +/-4.9% for 3, 5 and >=8 mm nodules, respectively.
      The 95% CI of intrascanner variability was within +/-28.6%, +/-13.4% and +/-2.6%
      for 3, 5 and >=8 mm nodules, respectively. CONCLUSION: Different 64-MDCT scanners
      in low-dose settings yield good agreement in volumetry of artificial pulmonary
      nodules between 5 mm and 12 mm in diameter. Inter- and intrascanner variability
      decreases at a larger nodule size to a maximum of 4.9% for >=8 mm nodules.
      ADVANCES IN KNOWLEDGE: The commonly accepted cut-off of 25% to determine nodule
      growth has the potential to be reduced for >=8 mm nodules. This offers the
      possibility of reducing the interval for repeated CT scans in lung cancer
      screenings.

PMID- 23884759
TI  - Iodine quantification with dual-energy CT: phantom study and preliminary
      experience with VX2 residual tumour in rabbits after radiofrequency ablation.
AB  - OBJECTIVE: The purpose of our study was to validate iodine quantification in a
      phantom study with dual-source dual-energy CT (DECT) and to apply this technique
      to differentiate benign periablational reactive tissue from residual tumour in
      VX2 carcinoma in rabbits after radiofrequency ablation (RFA). METHODS: We applied
      iodine quantification with DECT in a phantom and in VX2 carcinoma in rabbits
      after incomplete RFA to differentiate benign periablational reactive tissue from
      residual tumour and evaluated its efficacy in demonstrating response to
      therapeutic RFA. A series of tubes containing solutions of varying iodine
      concentration were scanned with DECT. The iodine concentration was calculated and
      compared with known true iodine concentration. Triple-phase contrast-enhanced
      DECT data on 24 rabbits with VX2 carcinoma were then assessed at Day 3 (n=6), 1
      week (n=6), 2 weeks (n=6) and 3 weeks (n=6) after incomplete RFA independently by
      2 readers. Dual-energy postprocessing was used to produce iodine-only images.
      Regions of interest were positioned on the iodine image over the lesion and, as a
      reference, over the aorta, to record iodine concentration in the lesion and in
      the aorta. The pathological specimens were sectioned in the same plane as DECT
      imaging, and the lesion iodine concentration and lesion-to-aorta iodine ratio of
      residual tumour and benign periablational reactive tissue were assessed. RESULTS:
      There was excellent correlation between calculated and true iodine concentration
      (r=0.999, p<0.0001) in the phantom study. The lesion iodine concentration and
      lesion-to-aorta iodine ratio in residual tumour were significantly higher than in
      benign periablational reactive tissue in the 2-week group during the arterial
      phase (AP) (p<0.01) and in the 3-week group during both the AP (p<0.05) and the
      portal venous phase (p<0.05). There was no significant difference between them
      with respect to the lesion iodine concentration or lesion-to-aorta iodine ratio
      in the 3-day and 1-week groups. CONCLUSION: Iodine quantification with DECT is
      accurate in a phantom study and can be used to differentiate benign
      periablational reactive tissue from residual tumour in VX2 carcinoma in rabbits
      after RFA. ADVANCES IN KNOWLEDGE: Iodine quantification with DECT may help in
      differentiating benign periablational reactive tissue from residual tumour in VX2
      carcinoma in rabbits after RFA.

PMID- 23884760
TI  - Assessment of genotoxic, cytotoxic, and protective effects of Salacia crassifolia
      (Mart. Ex. Schult.) G. Don. stem bark fractions in mice.
AB  - Salacia crassifolia (Mart. Ex. Schult.) G. Don., popularly known in Brazil as
      "bacupari", "cascudo", and "saputa", is a shrub of the Celastraceae family that
      is unique to the Brazilian Cerrado region. In folk medicine, this plant has been
      mainly used to treat skin cancer and gastric ulcers. In the present study, the
      genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of S. crassifolia
      stem bark fractions (hexane, ethyl acetate, and hydroalcoholic extracts) were
      evaluated using the mouse bone marrow micronucleus test. Our results showed that
      none of the S. crassifolia fractions led to a significant increase in the
      frequency of micronucleated polychromatic erythrocytes (MNPCE) (P > 0.05),
      suggesting the absence of genotoxicity. In the antigenotoxicity assessment, a
      significant decrease in the MNPCE frequency was observed in all fractions of this
      plant (P < 0.05), demonstrating its protective action against genotoxicity
      induced by mitomycin C (MMC), which was used as the positive control. Only the
      hexane fraction of S. crassifolia significantly decreased the poly- and
      normochromatic erythrocyte ratio (PCE/NCE) in all doses tested (P < 0.05),
      demonstrating its cytotoxic activity. In association with MMC, both ethyl acetate
      and hydroalcoholic fractions significantly increased the PCE/NCE ratio in almost
      all doses tested (P < 0.05), demonstrating the protective action of S.
      crassifolia against the cytotoxic effect of the positive control. In contrast,
      the hexane fraction presented a significant decrease in the PCE/NCE ratio in all
      treatments (P < 0.05), demonstrating an increase in this plant's cytotoxicity in
      mouse bone marrow cells. 

PMID- 23884761
TI  - Genomic selection of seed weight based on low-density SCAR markers in soybean.
AB  - With the development of molecular marker technology, crop breeding has been
      accelerated by marker-assisted selection for the improvement of quantitative
      traits. However, due to the traits' polygenic nature, traditional marker-assisted
      selection methods are ill-suited for identification of quantitative trait loci.
      Genomic selection (GS) was introduced into crop breeding to achieve more accurate
      predictions by considering all genes or markers simultaneously. We used dozens of
      sequence-characterized amplified region (SCAR) markers for genotyping soybean
      varieties, and we identified markers associated with hundred-seed weight. The
      best linear unbiased predictor and Bayesian liner regression methods were used to
      construct GS models to predict the hundred-seed weight trait based upon genotype
      information for trait selection. Both GS models showed good prediction
      performance in soybean, as the correlation coefficient between genomic estimated
      breeding values and true breeding values was as high as 0.904. This indicated
      that GS was performed effectively based on dozens of SCAR markers in soybean;
      these markers were of low density but easily detectable. Therefore, the
      combination of GS modeling and highly effective molecular marker technology
      involving SCAR markers can facilitate genetic breeding in soybean. This approach
      may also be suitable for genetic selection in other crops, such as wheat, maize,
      and rice. 

PMID- 23884762
TI  - Effects of polymorphisms in the bovine growth differentiation factor 9 gene on
      sperm quality in Holstein bulls.
AB  - Members of the transforming growth factor-beta (TGFbeta) superfamily are critical
      regulators of germ cell development that act as extracellular ligands of the
      signal transduction pathways regulating proliferation, differentiation,
      apoptosis, and other aspects of cell behavior. Growth differentiation factor 9
      (GDF9) is a member of the TGFbeta superfamily that plays a critical role in
      ovarian follicular development and ovulation rate in females; however, its role
      in the testis has not been well elucidated. Therefore, in this study we
      investigated the effects of GDF9 mutations on the quality of fresh and frozen
      semen of Holstein bulls. Two reported single nucleotide polymorphisms of GDF9,
      A485TA and A625C, were analyzed in 129 Holstein bulls. Analysis of variance
      revealed that the A485T polymorphism had significant effects on the acrosome
      integrity rate (P < 0.05), whereas the A625T polymorphism was significantly
      associated with sperm concentration (P < 0.05). In addition, a significant
      additive effect on sperm concentration was detected for the A485T polymorphism (P
      < 0.05), whereas the polymorphisms A485TA and A625C had significant dominant
      effects on acrosome integrity rate and sperm motility in frozen semen,
      respectively (P < 0.05). This study is the first to show a significant
      association of GDF9 with sperm quality traits, and the results implied that GDF9
      is involved in the initiation or maintenance of spermatogenesis; however, further
      verification is needed. 

PMID- 23884763
TI  - Tumor necrosis factor-alpha and -beta genetic polymorphisms as a risk factor in
      Saudi patients with vitiligo.
AB  - Vitiligo is an acquired depigmentary disorder of the skin, characterized by
      multiple susceptibility loci and genetic heterogeneity. The etiology of vitiligo
      is unknown but several hypotheses, including an autoimmune origin, have been
      proposed. Tumor necrosis factor (TNF)-alpha, a pleiotropic proinflammatory
      cytokine, has been shown to play a critical role in several autoimmune diseases
      including vitiligo. The aim of present study was to determine the association of
      TNF-alpha and -beta gene polymorphisms with vitiligo in Saudi patients. TNF-alpha
      and -beta genes were amplified in 123 Saudi patients and 200 matched controls
      using polymerase chain reaction to search for polymorphisms involved at positions
      -308, and intron 1 +252. The frequency of the TNF-alpha (-308) GA genotype was
      higher and the frequencies of the GG and AA genotypes were significantly lower in
      vitiligo patients compared to controls. These findings suggested that genotype GA
      positive individuals at position -308 of TNF-alpha are susceptible to vitiligo,
      whereas the GG and AA genotypes might exert a protective effect. The frequency of
      allele A (TNF-alpha 2-allele) was significantly higher and that of allele G (TNF
      alpha 1-allele) was lower in vitiligo patients compared to controls, indicating
      an association of allele A with susceptibility to vitiligo in Saudi patients. The
      results of our examination of TNF-beta (intron 1 +252) polymorphisms showed a
      significant increase in the frequency of the GG genotype and allele G (TNF-beta 1
      allele) in vitiligo patients, suggesting a susceptibility of the GG genotype and
      allele G for vitiligo. By contrast, the high frequency of the GA genotype in
      controls might indicate a protective effect. The results of the present study
      strongly support a link between TNF-alpha (-308) and -beta (intron 1 +252)
      polymorphisms and vitiligo in Saudi patients. 

PMID- 23884764
TI  - Lack of association between the interleukin 6 gene -174G>C polymorphism and
      colorectal cancer: evidence from a meta-analysis.
AB  - Interleukin 6 (IL6) is a pleiotropic cytokine involved in physiological processes
      and in a variety of human malignancies. It is thus a logical candidate for being
      a causative factor underlying colorectal cancer (CRC). The association between
      the IL6 -174G>C polymorphism and CRC has been widely evaluated; yet, there is a
      lack of agreement between studies on the role of this polymorphism in CRC. We
      performed a meta-analysis to evaluate this association signal. Articles published
      before May 10, 2012 were included in the meta-analysis. A total of 11 populations
      incorporating 6481 cases and 7935 controls were included in our analysis. A
      random-effect model was applied irrespective of between-study heterogeneity. Data
      and study quality were assessed in duplicate. Overall, the association of the 
      174G>C polymorphism with CRC was not significant in an allelic comparison model
      [odds ratio (OR) = 0.99; 95% confidence interval (95%CI) = 0.90-1.09; P = 0.827],
      a homozygote model (OR = 0.98; 95%CI = 0.83-1.15; P = 0.805), a dominant model
      (OR = 0.99; 95%CI = 0.87-1.13; P = 0.906), or a recessive model (OR = 0.97; 95%CI
      = 0.88-1.08; P = 0.610). Furthermore, the analyses of subgroups created based on
      common study design, genotyping methods, and ethnicity failed to find a
      significant association of this polymorphism with CRC. Therefore, our results
      collectively suggest that the IL6 -174G>C polymorphism might not be a potential
      candidate for CRC risk. 

PMID- 23884765
TI  - Cytogenetic and molecular analysis of infertile Chinese men: karyotypic
      abnormalities, Y-chromosome microdeletions, and CAG and GGN repeat polymorphisms
      in the androgen receptor gene.
AB  - Chromosome abnormalities, Y-chromosome microdeletions, and androgen receptor gene
      CAG and GGN repeat polymorphisms in infertile Chinese men featuring severe
      oligospermia and azoospermia were analyzed. Ninety-six fertile men and 189 non
      obstructive infertile men, including 125 patients with azoospermia and 64 with
      severe oligozoospermia, were studied. Seventeen infertile men (9.0%) carried a
      chromosome abnormality. Twenty (10.6%) carried a Y-chromosome microdeletion. In
      the remainder of the patients and controls, GGN and CAG repeats were sequenced.
      Short GGN repeats (n < 23) appeared to be associated with defective
      spermatogenesis, with the number of GGN repeats strongly correlated with sperm
      counts. No significant difference in CAG repeats was found between patients and
      controls, nor were CAG repeats correlated with sperm counts. However, for CAG
      repeats ranging between 24 and 25, there was a >2.5-fold risk (OR = 2.539, 95%CI
      = 1.206-5.344, P < 0.05) of severe oligospermia and azoospermia. Our results
      confirmed the significant role of chromosome abnormalities, Y-chromosome
      microdeletions, and GGN repeats in Chinese male infertility. 

PMID- 23884766
TI  - Gametocidal chromosomes enhancing chromosome aberration in common wheat induced
      by 5-azacytidine.
AB  - The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation,
      which is introduced into common wheat as a tool of chromosome manipulation for
      genetic improvement. The Gc chromosome functions similar to a restriction
      modification system in bacteria, in which DNA methylation is an important
      regulator. We treated root tips of wheat carrying Gc chromosomes with the
      hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were
      observed in these root tips. The frequency of aberrations differed in wheat
      containing different Gc chromosomes, suggesting different functions inducing
      chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome
      aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome
      aberration. Gc chromosome 3C induced different degrees of chromosome aberration
      in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26,
      demonstrating an inhibition function in common wheat. 

PMID- 23884767
TI  - Construction and analysis of a subtractive cDNA library of early embryonic
      development in duck.
AB  - Several studies have documented the process of early embryonic development in
      poultry; however, the molecular mechanisms underlying its developmental
      regulation are poorly understood, particularly in ducks. In this study, we
      analyzed differential gene expression of embryos 6 and 25 h following oviposition
      to determine which genes regulate the early developmental stage in ducks. Among
      216 randomly selected clones, 39 protein-encoding cDNAs that function in
      metabolism, transcription, transportation, proliferation/apoptosis, cell cycle,
      cell adhesion, and methylation were identified. Additionally, the full-length
      cDNA of the Nanog gene, encoding a 302-amino acid protein, was obtained.
      Quantitative real-time polymerase chain reaction analyses were performed to
      detect expression levels of the selected genes during early and late embryonic
      stages, which revealed that these genes are expressed in a particular spatial and
      temporal pattern. These results indicate that these genes may play pivotal roles
      in the process of area pellucida formation through a complex and precise
      regulatory network during development in duck embryos. 

PMID- 23884768
TI  - Use of microsatellite markers in molecular analysis of segregating populations of
      papaya (Carica papaya L.) derived from backcrossing.
AB  - Brazil is the world leader in papaya production. However, only a small number of
      cultivars are registered for commercial planting, mainly owing to delays in
      obtaining cultivars and the high costs of the field phase of breeding programs.
      These costs can be reduced when molecular tools are combined with conventional
      breeding methods. In the present study, we conducted a molecular analysis of a
      self-fertilized population of a first backcrossing generation of BC1S1 papaya
      plants via microsatellite markers both to monitor the level of homozygosity and
      the gene/allele transfer that confers the Golden trait (fruit color) and to
      assess the parental genomic proportion in the genotypes studied. Based on the
      analysis of 20 polymorphic microsatellite loci, 19 genotypes with the Golden
      trait belonging to BC1S1 were evaluated in addition to the parental genotypes.
      Genetic distance was estimated through weighted index. The genotypes were then
      grouped using the hierarchical nearest neighbor method, and the analysis of
      principal coordinates was used to measure the proportion of parental genomes in
      the segregating genotypes. The mean value of the inbreeding coefficient was 0.36.
      The analysis of the principal coordinates revealed that on average, 64% of the
      recurrent parent genome was present in the population. Together, the analyses
      allowed the selection of 3 individuals for the next backcross cycle (33BC1S1-18,
      34BC1S1-16, and 37BC1S1-10). These individuals had a higher proportion of the
      recurrent parent and were grouped close to the recurrent parent in the cluster
      analysis. 

PMID- 23884769
TI  - Prevalence of CYP2C8 polymorphisms in a North Indian population.
AB  - CYP2C8 is an important member of the cytochrome P450 family of enzymes; it
      affects the activity of various drugs used in routine clinical practice,
      including amiodarone, chloroquine, amodiaquine, and repaglinide, as well as
      endogenous compounds, such as arachidonic acid and retonic acid. It is also the
      main enzyme involved in the metabolism of the widely used anticancer drug
      Paclitaxel, which has a very narrow therapeutic index. There is evidence that
      single nucleotide polymorphisms in the CYP2C8 gene influence the adverse
      reactions and/or the efficacy of drugs metabolized by this enzyme. We examined
      the allele and genotype frequencies of widely studied functional polymorphisms of
      the CYP2C8 gene in a North Indian population. We assayed the genomic DNA of at
      least 251 healthy unrelated North Indians for CYP2C8*2, CYP2C8*3 (G416A, A1196G),
      and CYP2C8*4 genetic polymorphisms by RFLP technique. These results were compared
      to information on other populations. The allelic frequencies of CYP2C8*2,
      CYP2C8*3, and CYP2C8*4 were found to be 3, 4, and 4% respectively. The two
      CYP2C8*3 polymorphisms (G416A and A1196G) were found to be completely linked to
      each other. Allele frequencies of CYP2C8 genetic variants in northern Indians
      were found to have a distinct pattern that differs from that of southern Indian
      and other global populations. This is the first report from North India on CYP2C8
      polymorphisms. Ethnic differences with respect to polymorphisms are the molecular
      basis of interethnic variability in pharmacokinetics. Our study may help in
      rational use of drugs that are substrates for CYP2C8 in this population. 

PMID- 23884770
TI  - Search for methylation-sensitive amplification polymorphisms in mutant figs.
AB  - Fig (Ficus carica) breeding programs that use conventional approaches to develop
      new cultivars are rare, owing to limited genetic variability and the difficulty
      in obtaining plants via gamete fusion. Cytosine methylation in plants leads to
      gene repression, thereby affecting transcription without changing the DNA
      sequence. Previous studies using random amplification of polymorphic DNA and
      amplified fragment length polymorphism markers revealed no polymorphisms among
      select fig mutants that originated from gamma-irradiated buds. Therefore, we
      conducted methylation-sensitive amplified polymorphism analysis to verify the
      existence of variability due to epigenetic DNA methylation among these mutant
      selections compared to the main cultivar 'Roxo-de-Valinhos'. Samples of genomic
      DNA were double-digested with either HpaII (methylation sensitive) or MspI
      (methylation insensitive) and with EcoRI. Fourteen primer combinations were
      tested, and on an average, non-methylated CCGG, symmetrically methylated CmCGG,
      and hemimethylated hmCCGG sites accounted for 87.9, 10.1, and 2.0%, respectively.
      MSAP analysis was effective in detecting differentially methylated sites in the
      genomic DNA of fig mutants, and methylation may be responsible for the phenotypic
      variation between treatments. Further analyses such as polymorphic DNA sequencing
      are necessary to validate these differences, standardize the regions of
      methylation, and analyze reads using bioinformatic tools. 

PMID- 23884771
TI  - Evaluation of the antimutagenic and anticarcinogenic effects of inulin in vivo.
AB  - The incidence of colorectal cancer is growing worldwide. The characterization of
      compounds present in the human diet that can prevent the occurrence of colorectal
      tumors is vital. The oligosaccharide inulin is such a compound. The aim of this
      study was to evaluate the antigenotoxic, antimutagenic and anticarcinogenic
      effects of inulin in vivo. Our study is based on 3 assays that are widely used to
      evaluate chemoprevention (comet assay, micronucleus assay, and aberrant crypt
      focus assay) and tests 4 protocols of treatment with inulin (pre-treatment,
      simultaneous, post-treatment, and pre + continuous). Experiments were carried out
      in Swiss male mice of reproductive age. In order to induce DNA damage, we used
      the pro-carcinogenic agent 1,2-dimethylhydrazine. Inulin was administered orally
      at a concentration of 50 mg/kg body weight following the protocols mentioned
      above. Inulin was not administered to the control groups. Our data from the
      micronucleus assay reveal antimutagenic effects of inulin in all protocols. The
      percentage of inulin-induced damage reduction ranged from 47.25 to 141.75% across
      protocols. These data suggest that inulin could act through desmutagenic and bio
      antimutagenic mechanisms. The anticarcinogenic activity (aberrant crypt focus
      assay) of inulin was observed in all protocols and the percentages of damage
      reduction ranged from 55.78 to 87.56% across protocols. Further tests, including
      human trials, will be necessary before this functional food can be proven to be
      effective in the prevention and treatment of colon cancer. 

PMID- 23884772
TI  - Association between VEGF and eNOS gene polymorphisms and lumbar disc degeneration
      in a young Korean population.
AB  - Disturbances in blood flow to intervertebral discs (IVD) play an important role
      in IVD degeneration. Vascular endothelial growth factor (VEGF) and endothelial
      nitric oxide synthase (eNOS) are extremely important angiogenic factors for
      vasodilation and neovascularization. We investigated the relationship between
      single nucleotide polymorphisms (SNPs) of the VEGF and eNOS genes and genetic
      susceptibility to lumbar IVD degeneration in a young adult Korean population. Two
      hundred and forty-one participants (aged 18 to 30 years), with or without low
      back pain, were selected for the study. Magnetic resonance imaging was made of
      the lumbar spine in all participants. The patient group (N = 102) had low back
      pain clinically and lumbar IVD degeneration radiographically. The control group
      (N = 139) included subjects with and without low back pain; all were negative
      radiographically for lumbar IVD degeneration. Using PCR-RFLP analysis, we
      analyzed VEGF (-2578C>A, -1154G>A, -634G>C, and 936C>T) and eNOS (-786T>C, 4a4b
      and 894G>T) SNPs. We made combined analyses of the genes and performed haplotype
      analyses. There were no significant differences in the genotype distribution of
      polymorphisms of VEGF and eNOS genes among patients and controls. However, the
      frequency of VEGF -2578CA +AA/-634CC combined genotypes was significantly higher
      in patients when compared with controls [odds ratio (OR) = 21.00; 95% confidence
      interval (CI) = 2.590- 170.240]. The frequencies of the -2578A/-1154A/-634C/936C
      (OR = 3.831; 95%CI = 1.068-13.742), -2578A/-1154A/-634C (OR = 3.356; 95%CI =
      1.198-9.400), and -2578A/-634C/936C (OR = 10.820; 95%CI = 2.811-41.656)
      haplotypes were also significantly higher in patients than in controls. We
      conclude that the combined genotype VEGF -2578CA+AA/-634CC is a possible risk
      factor for IVD degeneration and the VEGF -2578A/-1154A/-634C/936C haplotype may
      increase the risk for development of IVD degeneration. Furthermore, the VEGF 
      634C allele appears to be associated with susceptibility to IVD degeneration. 

PMID- 23884773
TI  - Mapping codon usage in sequence regions flanking cleavage positions in the
      hepatitis A virus polyprotein.
AB  - To analyze the synonymous codon usage patterns of sequence regions flanking
      cleavage sites in the hepatitis A virus (HAV) polyprotein, the codon usage bias
      at codon positions and the synonymous codon usage in the target contexts of 30
      virus strains were estimated by two simple methods that were based on the values
      for relative synonymous codon usage. In addition, the pattern of synonymous codon
      usage was compared between the genomic sequences in HAV and those of its human
      host. Our results indicated that HAV adopts a combination of coincidence and
      antagonism with the synonymous codon usage in humans. This characteristic may
      help HAV to efficiently use the translational machinery in its human host. We
      also observed that codon usage exhibited a strong bias in some specific positions
      in these contexts, and that the underrepresented synonymous codons, CUA for Leu,
      ACG for Thr, GUA for Val, and UCG for Ser, are preferentially used in these
      positions. These underrepresented synonymous codons likely play roles in
      regulating the rate of protein translation and influencing the secondary
      structure of the sequence regions flanking the cleavage sites. 

PMID- 23884774
TI  - Isolation and characterization of new polymorphic microsatellite markers from the
      cuttlefish Sepiella maindroni (Cephalopoda; Sepiidae).
AB  - Fifteen new polymorphic microsatellite loci were developed for the cuttlefish
      Sepiella maindroni. In 32 individuals from a wild population of coastal Ningde,
      Fujian Province, China, the number of alleles at these loci varied between 2 and
      12, with an average of 5.86. The mean observed and expected heterozygosities were
      0.6917 and 0.5993, respectively. Among these polymorphic microsatellite loci, 4
      (SM2, SM19, SM40, and SM81) significantly deviated from Hardy-Weinberg
      equilibrium after sequential Bonferroni's correction. All of them were in linkage
      equilibrium. These microsatellite loci would be useful for evaluating the effect
      of releasing on extant S. maindroni populations as well as for investigating
      genetic diversity and population structure of this species. 

PMID- 23884775
TI  - One-year progression-free survival of therapy-naive patients with malignant
      pheochromocytoma and paraganglioma.
AB  - CONTEXT: The natural history of malignant pheochromocytoma or paragangliomas
      (MPP) remain unknown. OBJECTIVE: The primary aim of this study was to define
      progression-free survival at 1 year in therapy-naive patients with MPP. Secondary
      objectives were to characterize MPP and to look for prognostic parameters for
      progression at 1 year. DESIGN AND SETTING: The files of MPP followed up between
      January 2001 and January 2011 in two French Endocrine Networks were
      retrospectively reviewed. Therapy-naive patients were enrolled. MAIN OUTCOME
      MEASURES: The main outcome was progression-free survival at 1 year in therapy
      naive MPP patients according to Response Evaluation Criteria In Solid Tumors 1.1
      criteria. RESULTS: Ninety files (46 men, 44 women, mean age of 47.5 +/- 15 years)
      were reviewed on site by one investigator. MPP characteristics were as follows:
      presence of an adrenal primary, a mitotic count exceeding 5 per high power field,
      hypertension, inherited disease, and presence of bone metastases in 50%, 22%,
      60%, 49%, and 56% patients, respectively. Fifty-seven of the 90 patients with MPP
      (63%) were classified as therapy-naive. The median follow-up of these 57 patients
      was 2.4 years (range, 0.4-5.7). At 1 year, progression-free survival was 46% (CI
      95: 33-59). Twenty-six of 30 (87%) patients with progression at 1 year had
      exhibited progressive disease at the first imaging workup performed after a
      median of 5.7 months. No prognostic parameter was identified. CONCLUSIONS: Half
      of the therapy-naive patients with MPP achieved stable disease at 1 year. In
      symptom-free patients with MPP, a wait-and-see antitumor policy seems appropriate
      as first line. Modality for a prospective follow-up is proposed.

PMID- 23884776
TI  - Longitudinal decline of beta-cell function: comparison of a direct method vs a
      fasting surrogate measure: the Insulin Resistance Atherosclerosis Study.
AB  - CONTEXT: beta-Cell function (BCF) declines over the course of type 2 diabetes,
      but little is known about BCF changes across glucose tolerance status (GTS)
      categories, and comparisons of direct vs surrogate measures. OBJECTIVE: To assess
      longitudinal changes in BCF across GTS. DESIGN: The Insulin Resistance
      Atherosclerosis Study is a multicenter, observational, epidemiologic study.
      SETTING: Four clinical centers in the US that could identify subjects likely to
      have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).
      PATIENTS: We compared longitudinal changes in BCF in 1052 subjects over 5 years.
      Subjects were categorized according to baseline GTS: normal glucose tolerance
      (NGT: n = 547), impaired fasting glucose or impaired glucose tolerance (IFG/IGT:
      n = 341), and newly diagnosed type 2 diabetes (n = 164). INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: BCF was assessed from a frequently sampled iv glucose
      tolerance test (AIR, acute insulin response), and the homeostasis model
      assessment of BCF (HOMA B). RESULTS: NGT and IFG/IGT subjects increased their
      insulin secretion over time, whereas those with type 2 diabetes experienced
      either decline or little change in BCF. After adjustment for demographic
      variables and change in insulin resistance, change in HOMA B underestimated the
      magnitude of changes in BCF, as assessed by change in AIR. Relative to NGT, the 5
      year change in insulin secretion in IFG/IGT and type 2 diabetes was 31% and 70%
      lower (by HOMA B) and 50% and 80% lower (by AIR). CONCLUSIONS: The decline in BCF
      over time in IFG/IGT and type 2 diabetes may be more pronounced than previously
      estimated; HOMA B may underestimate this decline significantly.

PMID- 23884777
TI  - Paternal GNAS mutations lead to severe intrauterine growth retardation (IUGR) and
      provide evidence for a role of XLalphas in fetal development.
AB  - CONTEXT: Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism
      type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism
      (PPHP)/progressive osseous heteroplasia (POH) when paternally inherited. Recent
      studies have suggested that mutations on the paternal, but not the maternal, GNAS
      allele could be associated with intrauterine growth retardation (IUGR) and thus
      small size for gestational age. OBJECTIVES: The aim of the study was to confirm
      and expand these findings in a large number of patients presenting with either
      PHP-Ia or PPHP/POH. PATIENTS AND METHODS: We collected birth parameters (ie,
      gestational age, weight, length, and head circumference) of patients with either
      PHP-Ia (n = 29) or PPHP/POH (n = 26) with verified GNAS mutations. The parental
      allele carrying the mutation was assessed by investigating the parents or, when a
      de novo mutation was identified, through informative intragenic polymorphisms.
      RESULTS: Heterozygous GNAS mutations on either parental allele were associated
      with IUGR. However, when these mutations are located on the paternal GNAS allele,
      IUGR was considerably more pronounced than with mutations on the maternal allele.
      Moreover, birth weights were lower with paternal GNAS mutations affecting exons 2
      13 than with exon 1/intron 1 mutations. CONCLUSIONS: These data indicate that a
      paternally derived GNAS transcript, possibly XLalphas, is required for normal
      fetal growth and development and that this transcript affects placental
      functions. Thus, similar to other imprinted genes, GNAS controls growth and/or
      fetal development.

PMID- 23884778
TI  - Enhanced glucose metabolism is preserved in cultured primary myotubes from obese
      donors in response to exercise training.
AB  - CONTEXT: It was suggested that human cultured primary myotubes retain the
      metabolic characteristics of their donor in vitro. OBJECTIVES: The aim of the
      present study was to investigate whether the metabolic responses to endurance
      training are also conserved in culture. DESIGN AND VOLUNTEERS: Middle-aged obese
      subjects completed an 8-week supervised aerobic exercise training program in
      which vastus lateralis muscle biopsies were collected before and after training.
      MAIN OUTCOME MEASURES: Anthropometric and blood parameters, as well as aerobic
      capacity, were assessed before and after training. Muscle biopsies were either
      used for Western blot analysis or digested to harvest myogenic progenitors that
      were differentiated into myotubes. Glucose oxidation, palmitate oxidation, and
      glycogen synthesis assays were performed on myotubes before and after training.
      Gene expression was assessed by real-time quantitative PCR. RESULTS: Our data
      indicate that in parallel of in vivo improvement of whole-body aerobic capacity
      and glucose metabolism, biopsy-derived primary myotubes showed similar patterns
      in vitro. Indeed, glucose oxidation, glycogen synthesis, and inhibition of
      palmitate oxidation by glucose were enhanced in myotubes after training. This was
      associated with consistent changes in the expression of metabolism-linked genes
      such as GLUT1, PDK4, and PDHA1. Interestingly, no difference in myogenic
      differentiation capacity was observed before and after training. CONCLUSION:
      Aerobic exercise training is associated with metabolic adaptations in vivo that
      are preserved in human cultured primary myotubes. It can be hypothesized that
      skeletal muscle microenvironmental changes induced by endurance training lead to
      metabolic imprinting on myogenic progenitor cells.

PMID- 23884779
TI  - Is thyroid cancer recurrence risk increased after transplantation?
AB  - CONTEXT: An increased cancer mortality is reported in transplanted patients.
      OBJECTIVE: This multicentric study aimed to investigate the rate of thyroid
      cancer recurrence after transplantation. RESULTS: Sixty-eight patients (35
      male/33 female) with a history of both thyroid cancer and organ transplantation
      were recruited via two nationwide French networks. Histological analysis
      identified 58 papillary (88%), 5 follicular (7.5%), and 3 poorly differentiated
      cancer cases (4.5 %). Thirty-one patients (52%) presented high recurrence risk
      tumors. In the 36 patients with thyroid cancer diagnosed after transplantation,
      the 5-year disease-free survival (DFS) was 74.7% (SE: 7.3%). One patient died
      after progression of a poorly differentiated cancer. Persistent disease was
      observed in six high-risk patients. One of them underwent a second
      transplantation and disease remained stable after 5 years of follow-up. Thyroid
      cancer had been diagnosed before transplantation in 32 patients. One patient with
      cystic fibrosis and thyroid lung metastases at the time of lung transplantation
      underwent a 4-year remission. For the 31 patients in remission at the time of
      transplantation, the 5-year DFS was 93.1% (SE: 4.8%). Two patients with local
      recurrence presented subsequent remission. For the entire study population, the 5
      year and 9-year DFS were 81.9% (SE: 5.5%) and 75.6% (SE: 7.9%), respectively.
      Recurrence or persistent disease occurred in patients with high-risk tumors.
      CONCLUSIONS: The prognosis of thyroid cancer does not seem to be altered by
      transplantation. This suggests that a history of thyroid cancer should not be
      considered a contraindication.

PMID- 23884780
TI  - Differentiation of human embryonic stem cells into functional ovarian granulosa
      like cells.
AB  - CONTEXT: Granulosa cells are important for the development and maturation of
      oocytes. The dysfunction of granulosa cells may contribute to abnormal
      folliculogenesis and steroidogenesis. OBJECTIVE: Our objective was to establish
      an effective culture system to differentiate human embryonic stem cells (hESCs)
      into granulosa cells. DESIGN: For differentiation of hESCs to granulosa cells, we
      used multistep approaches comprising in vitro treatments with cocktails of growth
      factors. Expression of mesendoderm/intermediate plate mesoderm markers, and
      granulosa cell markers were analyzed by real time-PCR, Western blotting,
      immunofluorescence, and flow cytometry. The production of estradiol and anti
      Mullerian hormone (AMH) was analyzed by ELISA. RESULTS: Gene expression analyses
      showed the progress of hESCs to primitive streak-mesendoderm, intermediate plate
      mesoderm, and finally to functional granulosa-like cells that expressed the
      granulosa cell-specific forkhead transcription factor FOXL2, estrogen synthetase
      cytochrome P450 19A1 (CYP19A1), AMH, the type 2 AMH receptor (AMHR2), and the FSH
      receptor (FSHR). However, they did not express the LH receptor (LHR). Western
      blot showed that AMHR2 and CYP19A1 levels in differentiated hESCs were higher
      than in undifferentiated cells. Flow cytometry showed that the percentage of
      AMHR2-, FSHR-, and CYP19A1-positive cells increased to 36%, 12%, and 34%,
      respectively, after differentiation for 12 days. These granulosa-like cells were
      also capable of producing AMH and aromatizing testosterone to estradiol,
      suggesting that they were biologically functional. CONCLUSIONS: We successfully
      established an effective protocol to generate functional ovarian granulosa-like
      cells from hESCs. The derivation of these cells opens new avenues for the further
      study and potential application of these cells in human folliculogenesis and
      steroidogenesis.

PMID- 23884781
TI  - Interleukin-2 and lanreotide in the treatment of medullary thyroid cancer: in
      vitro and in vivo studies.
AB  - CONTEXT: To date no efficacious treatments are available for advanced medullary
      thyroid carcinoma (MTC). OBJECTIVE: We investigated in vitro and in vivo a new
      strategy for the therapy of MTC, combining human recombinant IL-2 with lanreotide
      (LAN), a somatostatin analog. METHODS: The in vitro effects of LAN on the
      sensitivity of TT cells, a MTC cell line, to IL-2-stimulated human peripheral
      blood mononuclear cells were determined by a lactate dehydrogenase release assay.
      In addition, we evaluated the toxicity, the effects on quality of life, and the
      antitumor activity of sc low-dose IL-2 in combination with LAN (90 mg every 28
      days) in a series of 6 patients with symptomatic and advanced MTC. RESULTS: The
      cytotoxicity of IL-2-activated peripheral blood mononuclear cells was
      significantly increased in TT cells treated with LAN or LAN plus IL-2 compared
      with that in TT cells without treatment. The therapy was well tolerated, and a
      statistically significant improvement of quality of life was observed in patients
      treated with the combination of LAN and IL-2. After 6 months of therapy, partial
      response and stable disease have been recorded in 2 and 3 patients, respectively,
      with a significant decrease in calcitonin levels in 3 patients. CONCLUSIONS: Both
      in vitro and in vivo evidence suggests that the combination of LAN and IL-2 may
      have a role in the management of advanced and symptomatic MTC. However, these
      preliminary data require further validation in larger randomized trials.

PMID- 23884782
TI  - A cellular and molecular basis for the selective desmopressin-induced ACTH
      release in Cushing disease patients: key role of AVPR1b receptor and potential
      therapeutic implications.
AB  - CONTEXT: Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs).
      The desmopressin stimulation test is used in the diagnosis and postsurgery
      prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms
      underlying the desmopressin-induced ACTH increase in patients with CD are poorly
      understood. OBJECTIVE: The objectives of this study were to determine, for the
      first time, whether desmopressin acts directly and exclusively on pituitary
      corticotropinoma cells to stimulate ACTH expression/release and to elucidate the
      cellular and molecular mechanisms involved in desmopressin-induced ACTH increase
      in CD. DESIGN: A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14
      nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were
      analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures
      derived from corticotropinomas, nonfunctioning pituitary adenomas,
      somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH
      secretion/expression, [Ca(2+)]i kinetics, and AVPR expression and/or
      proliferative response were evaluated. The relationship between AVPR expression
      and plasma adrenocorticotropin/cortisol levels obtained from desmopressin tests
      was assessed. RESULTS: Desmopressin affects all functional parameters evaluated
      in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These
      effects might be due to the dramatic elevation of AVPR1b expression levels found
      in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist
      completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b
      expression was positively correlated with elevated plasma adrenocorticotropin
      levels in corticotropinomas. CONCLUSIONS: The present results provide a cellular
      and molecular basis to support the desmopressin stimulation test as a reliable,
      specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our
      data indicate that AVPR1b is responsible for the direct/exclusive desmopressin
      stimulatory pituitary effects observed in CD, thus opening the possibility of
      exploring AVPR1b antagonists as potential therapeutic tools for CD treatment.

PMID- 23884783
TI  - Clinical review: Treatment of neurohypophyseal diabetes insipidus.
AB  - CONTEXT: In recent years, there have been several improvements in the treatment
      of neurohypophyseal diabetes insipidus (DI). They include new formulations of the
      vasopressin analog, desmopressin; a better understanding of the effect of fluid
      intake on dosing; and more information about treatments of infants, children, and
      pregnant women who present special challenges. This review aims to summarize past
      and current information relative to the safety and efficacy of treatments for the
      types of DI caused by a primary deficiency of vasopressin. EVIDENCE ACQUISITION:
      The review is based on publications identified primarily by a PubMed search of
      the international literature without limitations of date. EVIDENCE SYNTHESIS: In
      acute settings where fluid intake is determined by factors other than thirst,
      desmopressin should be given iv in doses that have a short duration of action and
      can be adjusted quickly in accordance with changes in hydration as indicated by
      plasma sodium. In ambulatory patients, the oral formulations (tablet or melt) are
      preferred for their convenience. If fluid intake is regulated normally by the
      thirst mechanism, the tablets or melt can be taken safely 1 to 3 times a day in
      doses sufficient to completely eliminate the polyuria. However, if fluid intake
      consistently exceeds replacement needs as evidenced by the development of
      hyponatremia, the dose should be reduced to allow higher than normal rates of
      urine output or intermittent breakthrough diuresis. This regimen is often
      indicated in infants or children because their rate of fluid intake tends to be
      greater than in adults. In all cases, the appropriate dose should be determined
      by titration, owing to considerable interindividual differences in
      bioavailability and antidiuretic effect. CONCLUSIONS: Desmopressin can provide
      effective and safe therapy for all patients with neurohypophyseal or gestational
      DI if given in doses and by a route that takes into account the determinants of
      fluid intake.

PMID- 23884784
TI  - PCR-RFLP-based typing for differentiation of Tomato yellow leaf curl virus
      (TYLCV) genotypes from infected host plants in Korea.
AB  - A polymerase chain reaction (PCR) using two sets of primers designed from
      published Tomato yellow leaf curl virus (TYLCV) genomes was developed to
      distinguish from the TYLCV-IL groups. The specificity of the two sets of primers
      was proven by testing against control TYLCV genomes and the symptomatic leaves of
      34 different tomato cultivars naturally infected with TYLCV in greenhouses. One
      set for TYLCV-IL strain-specific primers (TYLCV-UNI-F and TYLCV-UNI-R) amplified
      full-length genome fragments from all the 34 tomato cultivars. Another set for
      TYLCV-IL group-II strain-specific primers (TYLCV-GPII-F and TYLCV-GPII-R)
      amplified target DNA fragments from only 9 tomato cultivars. Digestion by BglII
      and EcoRV of the PCR amplicons produced restriction fragment length polymorphism
      pattern that distinguished the TYLCV-IL group-I with two fragments from the TYLCV
      IL group-II with no digested fragment. PCR coupled with BglII and EcoRV digestion
      confirmed that the 9 tomato cultivars were infected with the TYLCV-IL group-II
      and the remained 25 tomato cultivars were infected with the TYLCV-IL group-I. 

PMID- 23884785
TI  - Total trihalomethanes in public drinking water supply and birth outcomes: a cross
      sectional study.
AB  - Reproductive effects of long-term, low-dose exposure to disinfectant by-products
      have not been consistently documented in large populations despite the known
      toxicity of high exposures and the wide-spread occurrence of low concentrations
      in public drinking water. We investigated the effect of low-dose exposure to
      total trihalomethanes (TTHM) on birth weight and gestational term in New York
      State. All singleton live births from 1998 through 2003 in 62 counties in New
      York State were linked with public water supply (PWS) system boundaries based on
      mother's residential address on birth certificate. Using the data from public
      water supply system, TTHM measurements were assigned geographically and
      temporally to each birth record linked with PWS boundary. Individual level
      maternal information including mother's race, ethnicity, education, employment
      status, smoking, age, along with adequacy of prenatal care utilization and
      infant's gender was used in a logistic model to adjust for potential confounding.
      A small non-linear association was detected between TTHM exposure and low birth
      weight (<2,500 g) births (OR 1.14; 95 % confidence interval (CI) 1.08-1.21),
      preterm births (OR 1.14; 95 % CI 1.08-1.20) and for small for gestational age
      births (OR 1.10; 95 % CI 1.04-1.16) suggesting a small increase in risk for these
      birth outcomes with chronic low maternal exposure to drinking water containing
      trihalomethanes. Maternal exposure to TTHMs during pregnancy may be associated
      with low birth weight, preterm births and small for gestational age births.

PMID- 23884788
TI  - Early life loss and trauma: eating disorder onset in a middle-aged male--a case
      study.
AB  - The onset of an eating disorder in middle-age men is poorly researched as are
      eating disorders in men generally. Therefore, life events that influence eating
      disorders in men, including delayed onset of an eating disorder remains unknown.
      Given the limited understanding of males with eating disorders and limited access
      to large samples of men with eating disorders, an in-depth analysis of a single
      case of a male in middle age with an eating disorder was chosen to gain insight
      and understanding into this phenomenon. A Life History approach explored the case
      of Joseph (pseudonym), who was diagnosed at age 44 years with an Eating Disorder
      Not Otherwise Specified. Data were collected through (a) life course open-ended
      questioning through interviews, (b) written statements, and (c) comments on
      transcripts. Three themes emerged, loss and unworthiness, becoming bigger, and
      wanting to change reflecting eating behaviors associated with attachment
      disruption, loss and trauma, body dissatisfaction, and negative affect. Later in
      life, an emotional "tipping point" precipitated an eating disorder. Results
      indicate traumatic loss leading to early attachment disruption as influential in
      Joseph's delayed onset of an eating disorder. The value of thorough narrative
      life histories during therapy when eating disorders occur late in life is
      discussed as well as the significance for men. 

PMID- 23884787
TI  - Epigallocatechin-3-gallate regulates the expression of Kruppel-like factor 4
      through myocyte enhancer factor 2A.
AB  - Epigallocatechin-3-gallate (EGCG), a powerful antioxidant and free ion scavenger
      found in green tea, exhibits inhibitory effects on different stages of
      tumorigenesis. Within gastric cancer cells, the transcription factor Kruppel-like
      factor 4 (KLF4) is downregulated, and it is possible that EGCG exerts its anti
      tumorigenic function through modulation of KLF4 expression. In order to examine
      the effects of EGCG on KLF4 in a gastric tumor model, we treated the gastric
      cancer cell line NCI-N87 with EGCG. We found that EGCG treatment results in
      increased expression of KLF4 and alters expression of the KLF4 target genes p21,
      CDK4, and cyclin D1. EGCG inhibits the growth of NCI-N87 cells in a time- and
      dose-dependent manner through arresting the cell cycle in the G0/G1 phase.
      Furthermore, terminal deoxynucleotidyl transferase dUTP nick end labeling assay
      and 4',6-diamidino-2-phenylindole staining revealed that EGCG is able to promote
      apoptosis of NCI-N87 cells. The suppressive effects of EGCG on cell growth and
      cell cycle protein expression are eliminated by decreasing KLF4 mRNA using siRNA
      and are magnified by overexpressing KLF4. Using KLF4 reporter constructs, we
      verified that the elevated expression induced by EGCG was mediated by increasing
      levels of activated MEF2A, which bound to the promoter region of KLF4. Taken
      together, this is the first time that EGCG is reported to increase the expression
      of KLF4, suggesting a novel mechanisms in gastric cancer treatment. 

PMID- 23884789
TI  - Men's perceptions and attitudes toward the partner with premenstrual syndrome.
AB  - This study focused on the young adult men's perceptions and behavior toward their
      women partners who they acknowledged as experiencing the effects of premenstrual
      syndrome (PMS). A qualitative study was conducted, framed by social
      constructivism, where individual interviews with 20 young Brazilian men aged 21
      to 29 years were analyzed thematically. Four descriptive categories to express
      the men's experiences: (a) men's observations on partner's behavior changes, (b)
      early in the relationship: apprehension and confusion, (c) knowledge about PMS
      led men to better understanding about changes, and (d) need for support from a
      health care provider and medication. The men's perceptions and behavior toward
      their partners were strongly influenced by biomedical conceptions of PMS.
      Participants believed that their partners' emotions and behaviors were determined
      by PMS during some days of the month, consequently PMS had affected the couple's
      relationship. Another consequence of such medicalization was that women's
      complaints about PMS were rendered invisible except when viewed as a serious
      medical problem requiring cure, rather than a part of women's cyclical patterns.
      It is the case that the systematic description of men's perceptions about their
      partner's PMS provides an approach to this topic in educational and health care
      activities, with the potential to improve gender relations. 

PMID- 23884786
TI  - Do reciprocal interactions between cell stress proteins and cytokines create a
      new intra-/extra-cellular signalling nexus?
AB  - Cytokine biology began in the 1950s, and by 1988, a large number of cytokines,
      with a myriad of biological actions, had been discovered. In 1988, the basis of
      the protein chaperoning function of the heat shock, or cell stress, proteins was
      identified, and it was assumed that this was their major activity. However, since
      this time, evidence has accumulated to show that cell stress proteins are
      secreted by cells and can stimulate cellular cytokine synthesis with the
      generation of pro- and/or anti-inflammatory cytokine networks. Cell stress can
      also control cytokine synthesis, and cytokines are able to induce, or even
      inhibit, the synthesis of selected cell stress proteins and may also promote
      their release. How cell stress proteins control the formation of cytokines is not
      understood and how cytokines control cell stress protein synthesis depends on the
      cellular compartment experiencing stress, with cytoplasmic heat shock factor 1
      (HSF1) having a variety of actions on cytokine gene transcription. The
      endoplasmic reticulum unfolded protein response also exhibits a complex set of
      behaviours in terms of control of cytokine synthesis. In addition, individual
      intracellular cell stress proteins, such as Hsp27 and Hsp90, have major roles in
      controlling cellular responses to cytokines and in controlling cytokine synthesis
      in response to exogenous factors. While still confusing, the literature supports
      the hypothesis that cell stress proteins and cytokines may generate complex intra
      and extra-cellular networks, which function in the control of cells to external
      and internal stressors and suggests the cell stress response as a key parameter
      in cytokine network generation and, as a consequence, in control of immunity. 

PMID- 23884790
TI  - Are there racial disparities in psychotropic drug use and expenditures in a
      nationally representative sample of men in the United States? Evidence from the
      Medical Expenditure Panel Survey.
AB  - This article sought to determine whether racial disparities exist in psychotropic
      drug use and expenditures in a nationally representative sample of men in the
      United States. Data were extracted from the 2000-2009 Medical Expenditure Panel
      Survey, a longitudinal survey that covers the U.S. civilian noninstitutionalized
      population. Full-Year Consolidated, Medical Conditions, and Prescribed Medicines
      data files were merged across 10 years of data. The sample of interest was
      limited to adult males aged 18 to 64 years, who reported their race as White,
      Black, Hispanic, or Asian. This study employed a pooled cross-sectional design
      and a two-part probit generalized linear model for analyses. Minority men
      reported a lower probability of psychotropic drug use (Black=-4.3%, 95%
      confidence interval [CI]=[-5.5, -3.0]; Hispanic=-3.8%, 95% CI=[-5.1, -2.6];
      Asian=-4.5%, 95% CI=[-6.2, -2.7]) compared with White men. After controlling for
      demographic, socioeconomic, and health status variables, there were no
      statistically significant race differences in drug expenditures. Consistent with
      previous literature, racial and ethnic disparities in the use of psychotropic
      drugs present problems of access to mental health care and services.

PMID- 23884791
TI  - Prospective memory in children and chimpanzees.
AB  - Prospective memory (PM) involves remembering to do something at a specific time
      in the future. Here, we investigate the beginnings of this ability in young
      children (3-year-olds; Homo sapiens) and chimpanzees (Pan troglodytes) using an
      analogous task. Subjects were given a choice between two toys (children) or two
      food items (chimpanzees). The selected item was delivered immediately, whereas
      the unselected item was hidden in an opaque container. After completing an
      ongoing quantity discrimination task, subjects could request the hidden item by
      asking for it (children) or by pointing to the container and identifying the item
      on a symbol board (chimpanzees). Children and chimpanzees showed evidence of
      prospective-like memory in this task, as evidenced by successful retrieval of the
      item at the end of the task, sometimes spontaneously with no prompting from the
      experimenter. These findings contribute to our understanding of PM from an
      ontogenetic and comparative perspective. 

PMID- 23884792
TI  - Endoscopic submucosal dissection using a thulium laser: preliminary results of a
      new method for treatment of gastric epithelial neoplasia.
AB  - BACKGROUND AND STUDY AIM: This study aimed to evaluate the feasibility of a novel
      laser system for endoscopic submucosal dissection (ESD) of gastric epithelial
      neoplasia. PATIENTS AND METHODS: A total of 10 patients underwent ESD by a single
      expert endoscopist. A thulium 2-MUm wavelength laser system was used for ESD
      procedures. Instead of using endoscopy knives, a 550-MUm flexible silica fiber
      was inserted through the working channel of the endoscope. RESULTS: In all
      patients, ESD was completed using only the thulium laser, without the need for
      endoscopy knives. The median total procedure time was 49 minutes (range 35 -
      203). In 8 /10 patients (80 %), no active bleeding was observed during ESD. The
      final pathologic mapping revealed low-grade dysplasia (n = 4), differentiated
      adenocarcinoma (n = 5), and signet ring cell carcinoma (n = 1). Curative
      resection was achieved in 9 /10 patients (90 %). There were no significant
      complications, such as delayed bleeding or perforation. CONCLUSIONS: The thulium
      laser system was feasible in ESD of gastric epithelial neoplasia.

PMID- 23884793
TI  - Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of
      risk factors providing rationale for therapy decisions.
AB  - BACKGROUND AND STUDY AIM: Population screening for colorectal cancer (CRC) is
      expected to increase the number of pT1 CRCs. Local excision is an attractive
      treatment option, but is only oncologically safe in the absence of lymph node
      metastasis (LNM). A systematic review of the predictive value of pathological
      risk factors for LNM in pT1 CRC was conducted to provide data for an evidence
      based decision regarding follow-up or radical surgery after local excision.
      METHODS: PubMed was searched for reports on predictors of LNM in pT1 CRC.
      Published papers written in English and containing at least 50 patients were
      included. Meta-analyses were performed using Review Manager 5.1. RESULTS: A total
      of 17 studies were included involving a total of 3621 patients with available
      nodal status. The strongest independent predictors of LNM were lymphatic invasion
      (relative risk [RR] 5.2, 95 % confidence interval [CI] 4.0 - 6.8), submucosal
      invasion >= 1 mm (RR 5.2, 95 %CI 1.8 - 15.4), budding (RR 5.1, 95 %CI 3.6 - 7.3),
      and poor histological differentiation (RR 4.8, 95 %CI 3.3 - 6.9). Limitations of
      the study were: results could not be stratified according to location in the
      colon or rectum; very early tumors removed by polypectomy without surgical
      resection were not included in the meta-analysis; and included studies were
      primarily from Asian countries and results therefore need to be verified in
      Western populations. CONCLUSION: The absence of lymphatic invasion, budding,
      submucosal invasion >= 1 mm, and poor histological differentiation were each
      associated with low risk of LNM. Risk stratification models integrating these
      factors need to be investigated further.

PMID- 23884794
TI  - Risk stratification to predict pain during unsedated colonoscopy: results of a
      multicenter cohort study.
AB  - BACKGROUND AND STUDY AIMS: Colonoscopy without sedation has several advantages
      over sedated colonoscopy, but a considerable proportion of patients experience
      pain. The aim of this study was to develop a risk stratification model of pre
      examination risk factors to enable targeted sedation during colonoscopy. PATIENTS
      AND METHODS: Between October 2011 and January 2012, consecutive outpatients who
      were willing to start colonoscopy without sedation at 11 Norwegian centers were
      prospectively recruited. Patients recorded pain on a validated 4-point scale
      (none, slight, moderate, or severe pain). Potential risk factors for a painful
      procedure (defined as moderate or severe pain) were evaluated using multivariate
      logistic regression analyses, and the area under the receiver operating
      characteristics curve (AUROC) was calculated to assess the discriminatory ability
      of the derived model. RESULTS: A total of 1198 patients (635 men and 563 women)
      were included. Seven independent, pre-procedural risk factors for patient pain
      were identified: female sex, age < 40 years, previous abdominal surgery,
      abdominal pain as indication for colonoscopy, anticipation of pain, previous
      painful colonoscopy, and a history of diverticulitis. In patients with 0, 1, 2,
      or >= 3 risk factors, a painful colonoscopy was experienced by 35 %, 43 %, 52 %,
      and 63 % of women and 18 %, 24 %, 35 %, and 63 % of men, respectively. The model
      showed modest discrimination abilities (AUROC = 0.69). CONCLUSION: Female sex was
      a strong risk factor for pain during colonoscopy, and sedation or analgesia
      should be considered for all women prior to colonoscopy. For male patients, the
      presence of multiple risk factors should encourage the endoscopist to offer
      sedation.

PMID- 23884795
TI  - Endoscopic submucosal dissection of esophageal cancer using the Mucosectom2
      device: a feasibility study.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is being
      increasingly used for superficial esophageal cancers. However, esophageal ESD is
      technically difficult, time consuming, and less safe compared with endoscopic
      mucosal resection (EMR). To perform ESD safely and more efficiently, various
      types of knives have been developed. This study compared the efficacy of our
      newly developed device, Mucosectom2, with that of conventional devices for
      esophageal ESD. PATIENTS AND METHODS: Between May 2007 and February 2011, ESD was
      performed for 172 esophageal lesions. Of these, 120 lesions were treated by
      conventional devices only, whereas 52 lesions were treated by conventional
      devices and the Mucosectom2. Procedure time, en bloc and R0 resection rates, and
      adverse events were retrospectively compared between the conventional and
      Mucosectom2 groups. RESULTS: The median procedure time was 48.0 minutes in the
      conventional group and 21.5 minutes in the Mucosectom2 group; the procedure time
      was significantly shorter in the Mucosectom2 group than in the conventional group
      (P < 0.0001). The en bloc and R0 resection rates were lower in the conventional
      group than those in the Mucosectom2 group, although these differences were not
      significant. The rate of exposure of the muscle layer in the Mucosectom2 group
      was significantly lower than in the conventional group (P = 0.04). The rates of
      perforation and postoperative bleeding were not significantly different between
      the two groups. CONCLUSIONS: This feasibility study suggests that, compared with
      conventional ESD devices, the Mucosectom2 may decrease the time required for
      esophageal ESD. Although our groups appeared comparable, they were studied at
      different times. Endoscopic expertise and endoscope quality may have differed
      during these periods, thereby affecting the results of our study. A prospective
      trial is therefore required to confirm our results.

PMID- 23884796
TI  - Isolation of human lymphatic malformation endothelial cells, their in vitro
      characterization and in vivo survival in a mouse xenograft model.
AB  - Human lymphatic vascular malformations (LMs), also known as cystic hygromas or
      lymphangioma, consist of multiple lymphatic endothelial cell-lined lymph
      containing cysts. No animal model of this disease exists. To develop a mouse
      xenograft model of human LM, CD34(Neg)CD31(Pos) LM lymphatic endothelial cells
      (LM-LEC) were isolated from surgical specimens and compared to foreskin
      CD34(Neg)CD31(Pos) lymphatic endothelial cells (LECs). Cells were implanted into
      a mouse tissue engineering model for 1, 2 and 4 weeks. In vitro LM-LECs showed
      increased proliferation and survival under starvation conditions (P < 0.0005 at
      48 h, two-way ANOVA), increased migration (P < 0.001, two-way ANOVA) and formed
      fewer (P = 0.029, independent samples t test), shorter tubes (P = 0.029,
      independent samples t test) than foreskin LECs. In vivo LM-LECs implanted into a
      MatrigelTM-containing mouse chamber model assembled to develop vessels with
      dilated cystic lumens lined with flat endothelium, morphology similar to that of
      clinical LMs. Human foreskin LECs failed to survive implantation. In LM-LEC
      implanted chambers the percent volume of podoplanin(Pos) vessels was 1.18 +/-
      2.24 % at 1 week, 6.34 +/- 2.68 % at 2 weeks and increasing to 7.67 +/- 3.60 % at
      4 weeks. In conclusion, the significantly increased proliferation, migration,
      resistance to apoptosis and decreased tubulogenesis of LM-LECs observed in vitro
      is likely to account for their survival and assembly into stable LM-like
      structures when implanted into a mouse vascularised chamber model. This in vivo
      xenograft model will provide the basis of future studies of LM biology and
      testing of potential pharmacological interventions for patients with lymphatic
      malformations.

PMID- 23884797
TI  - Role of visual evoked potentials in the assessment and management of optic
      pathway gliomas in children.
AB  - OBJECTIVE: The aim of this study is to investigate the role of pattern reversal
      visual evoked potentials (pVEPs) in the screening and monitoring of optic pathway
      gliomas (OPGs) in children with and without neurofibromatosis type 1. METHODS: A
      review of the English literature published between 1980 and 2012 was performed,
      with comparison of results of retro- and prospective studies. RESULTS: Pattern
      reversal VEPs have a high sensitivity (85.7-100 %) for the diagnosis of OPGs,
      moreover they are safe and cost-effective. Conversely, they have a low
      specificity (43-83 %) and are not widely available. Besides, pattern reversal VEP
      results can be unreliable in young children, because of the need for a good
      cooperation. The studies that were analyzed have drawbacks, including the small
      sample size, the retrospective design, the differences in gold standard for
      diagnosis, the different interpretation of small changes in VEP results and the
      lack of control groups. CONCLUSION: There is still debate about the gold standard
      for the screening and follow-up of OPGs. The added value of pVEPs to the
      ophthalmic examination is controversial. Randomized controlled trials or
      prospective multicentre studies are necessary to assess with sufficient accuracy
      the sensitivity and specificity of pattern reversal VEPs in the screening for
      OPGs and its follow-up.

PMID- 23884798
TI  - The 2013 Frank Stinchfield Award: Diagnosis of infection in the early
      postoperative period after total hip arthroplasty.
AB  - BACKGROUND: Diagnosis of periprosthetic joint infection (PJI) can be difficult in
      the early postoperative period after total hip arthroplasty (THA) because normal
      cues from the physical examination often are unreliable, and serological markers
      commonly used for diagnosis are elevated from the recent surgery.
      QUESTIONS/PURPOSES: The purposes of this study were to determine the optimal
      cutoff values for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
      synovial fluid white blood cell (WBC) count, and differential for diagnosing PJI
      in the early postoperative period after primary THA. METHODS: We reviewed 6033
      consecutive primary THAs and identified 73 patients (1.2%) who underwent
      reoperation for any reason within the first 6 weeks postoperatively. Thirty-six
      of these patients were infected according to modified Musculoskeletal Infection
      Society criteria. Mean values for the diagnostic tests were compared between
      groups and receiver operating characteristic curves generated along with an area
      under the curve (AUC) to determine test performance and optimal cutoff values to
      diagnose infection. RESULTS: The best test for the diagnosis of PJI was the
      synovial fluid WBC count (AUC = 98%; optimal cutoff value 12,800 cells/MUL)
      followed by the CRP (AUC = 93%; optimal cutoff value 93 mg/L), and synovial fluid
      differential (AUC = 91%; optimal cutoff value 89% PMN). The mean ESR (infected =
      69 mm/hr, not infected = 46 mm/hr), CRP (infected = 192 mg/L, not infected = 30
      mg/L), synovial fluid WBC count (infected = 84,954 cells/MUL, not infected = 2391
      cells/MUL), and differential (infected = 91% polymorphonuclear cells [PMN], not
      infected = 63% PMN) all were significantly higher in the infected group.
      CONCLUSIONS: Optimal cutoff values for the diagnosis of PJI in the acute
      postoperative period were higher than those traditionally used for the diagnosis
      of chronic PJI. The serum CRP is an excellent screening test, whereas the
      synovial fluid WBC count is more specific.

PMID- 23884799
TI  - Collaborative partnerships and the future of global orthopaedics.

PMID- 23884800
TI  - CORR Insights (r): Hip resurfacing does not improve proprioception compared with
      THA.

PMID- 23884801
TI  - Do jumbo cups cause hip center elevation in revision THA? A computer simulation.
AB  - BACKGROUND: Acetabular revision THA with use of a large (jumbo) cup is an
      effective treatment for many cavitary and segmental peripheral bone defects.
      However, the jumbo cup may result in elevation of the hip center and protrusion
      through the anterior acetabular wall as a result of the oversized geometry of the
      jumbo cup compared with the physiologic acetabulum. QUESTIONS/PURPOSES: The
      purpose of this computer simulation was to determine how much elevation of the
      hip center and anterior wall protrusion occurs in revision THA with use of a
      jumbo cup technique in which the inferior edge of the jumbo cup is placed at the
      inferior acetabular rim and the superior edge of the jumbo cup is placed against
      host bone at the superior margin of a posterosuperior bone defect. METHODS: Two
      hundred sixty-five pelvic CT scans were analyzed by custom CT analytical
      software. The computer simulated oversized reaming. The vertical and anterior
      reamer center shifts were measured, and anterior column bone removal was
      determined. RESULTS: The computer simulation demonstrated that the hip center
      shifted 0.27 mm superiorly and 0.02 mm anteriorly, and anterior column bone
      removal increased 0.86 mm for every 1-mm increase in reamer diameter.
      CONCLUSIONS: Our results indicate that the jumbo cup technique results in hip
      center elevation despite placement of the cup adjacent to the inferior
      acetabulum. For a hypothetical increase from a 54-mm socket to a 72-mm socket, as
      one might see in the context of the revision of a failed THA, our model would
      predict an elevation of the hip center of approximately 5 mm and loss of
      approximately 15 mm of anterior column bone. This suggests that an increase in
      femoral head length may be needed to compensate for the hip center elevation
      caused by the use of a large jumbo cup in revision THA. A jumbo cup may also
      result in protrusion through the anterior wall.

PMID- 23884803
TI  - Does adding antibiotics to cement reduce the need for early revision in total
      knee arthroplasty?
AB  - BACKGROUND: There is considerable debate about whether antibiotic-loaded bone
      cement should be used for fixation of TKAs. While antibiotics offer the
      theoretical benefit of lowering early revision due to infection, they may weaken
      the cement and thus increase the likelihood of aseptic loosening, perhaps
      resulting in a higher revision rate. QUESTIONS/PURPOSES: We (1) compared the
      frequency of early knee revision arthroplasty in patients treated with antibiotic
      loaded or non-antibiotic-loaded cement for initial fixation, (2) determined
      effects of age, sex, comorbidities, and surgeons' antibiotic-loaded cement usage
      patterns on revision rate, and (3) compared causes of revision (aseptic or
      septic) between groups. METHODS: Our study sample was taken from the Canadian
      Joint Replacement Registry and Canada's Hospital Morbidity Database and included
      cemented TKAs performed between April 1, 2003, and March 31, 2008, including
      20,016 TKAs inserted with non-antibiotic-loaded cement and 16,665 inserted with
      antibiotic-loaded cement. Chi-square test was used to compare the frequency of
      early revisions between groups. Cox regression modeling was used to determine
      whether revision rate would change by age, sex, comorbidities, or use of
      antibiotic-loaded cement. Similar Cox regression modeling was used to compare
      cause of revision between groups. RESULTS: Two-year revision rates were similar
      between the groups treated with non-antibiotic-loaded cement and antibiotic
      loaded cement (1.40% versus 1.51%, p = 0.41). When controlling for age, sex,
      comorbidities, diabetes, and surgeons' antibiotic-loaded cement usage patterns,
      the revision risk likewise was similar between groups. Revision rates for
      infection were similar between groups; however, there were more revisions for
      aseptic loosening in the group treated with non-antibiotic-loaded cement (p =
      0.02). CONCLUSIONS: The use of antibiotic-loaded cement in TKAs performed for
      osteoarthritis has no clinically significant effect on reducing revision within 2
      years in patients who received perioperative antibiotics. Longer followup and
      confirmation of these findings with other national registries are warranted.

PMID- 23884802
TI  - Trabecular metal in total knee arthroplasty associated with higher knee scores: a
      randomized controlled trial.
AB  - BACKGROUND: Porous tantalum is an option of cementless fixation for TKA, but
      there is no randomized comparison with a cemented implant in a mid-term followup.
      QUESTIONS/PURPOSES: We asked whether a tibial component fixed by a porous
      tantalum system might achieve (1) better clinical outcome as reflected by the
      Knee Society Score (KSS) and WOMAC Osteoarthritis Index, (2) fewer complications
      and reoperations, and (3) improved radiographic results with respect to aseptic
      loosening compared with a conventional cemented implant. METHODS: We randomized
      145 patients into two groups, either a porous tantalum cementless tibial
      component group (Group 1) or cemented conventional tibial component in posterior
      cruciate retaining TKA group (Group 2). Patients were evaluated preoperatively
      and 15 days, 6 months, and 5 years after surgery, using the KSS and the WOMAC
      index. Complications, reoperations, and radiographic failures were tallied.
      RESULTS: At 5-year followup the KSS mean was 90.4 (range, 68-100; 95% CI, +/-
      1.6) for Group 1, and 86.5 (range, 56-99; 95% CI, +/- 2.4) for Group 2. The
      effect size, at 95% CI for the difference between means, was 3.88 +/- 2.87. The
      WOMAC mean was 15.1 (range, 0-51; 95% CI, +/- 2.6) for the Group 1, and 19.1
      (range, 4-61; 95% CI, +/- 2.9) for Group 2. The effect size for WOMAC was -4.0 +/
      3.9. There were no differences in the frequency of complications or in aseptic
      loosening between the two groups. CONCLUSIONS: Our data suggest there are small
      differences between the uncemented porous tantalum tibial component and the
      conventional cemented tibial component. It currently is undetermined whether the
      differences outweigh the cost of the implant and the results of their long-term
      performance.

PMID- 23884804
TI  - Durable fixation achieved with medialized, high hip center cementless THAs for
      Crowe II and III dysplasia.
AB  - BACKGROUND: A high hip center total hip arthroplasty (THA) for dysplasia allows
      more complete socket coverage by native bone at the expense of abnormal hip
      biomechanics. Despite poor results with cemented components, intermediate-term
      results with cementless cups at a high hip center have been promising, but there
      are few reports at long-term followup without bone graft. QUESTIONS/PURPOSES: The
      purpose of this study was to examine (1) survivorship; 2) radiographic results;
      and 3) hip scores at a minimum of 10 years for patients treated with high hip
      center cementless THA for Crowe II and III dysplasia without bone graft. METHODS:
      We reviewed charts and radiographs of 32 patients with Crowe II or III dysplasia
      who were treated with high hip center cementless THA; at a mean followup of 12
      years (range, 10-21 years), 23 patients (27 hips) were available for review. We
      sought to medialize cups to the inner table to achieve bony coverage of > 75%. At
      final followup, the WOMAC and Harris hip scores were recorded. Radiographic
      analysis including computerized wear evaluation was performed. Radiographic
      parameters were compared with a control group of 23 patients with Crowe I
      dysplasia who had cementless cups placed at an anatomic hip center; among the
      high hip center reconstructions, we also compared wear between those in the
      superolateral and superomedial quadrants. RESULTS: Kaplan-Meier survivorship for
      all-cause revisions was 97% (95% confidence interval, 79%-99%) in the high hip
      center group; this was no different from the anatomic hip center group. There
      were no revisions for acetabular loosening. Wear rates did not differ
      significantly between the high hip center and the control group, but lateralized
      high hip centers were associated with higher (p = 0.002) wear. Hip scores were
      excellent in both groups. CONCLUSIONS: In Crowe II and III dysplasia, a high hip
      center cementless cup obviates the need for bone graft and provides durable
      fixation beyond 10 years. Medialization of these reconstructions seems important
      to decrease wear.

PMID- 23884805
TI  - CORR Insights(r): Staphylococcus aureus colonization among arthroplasty patients
      previously treated by decolonization protocol: a pilot study.

PMID- 23884806
TI  - Challenges in outcome measurement: clinical research perspective.
AB  - BACKGROUND: Comparative effectiveness research evaluates treatments as actually
      delivered in routine clinical practice, shifting research focus from efficacy and
      internal validity to effectiveness and external validity ("generalizability").
      Such research requires accurate assessments of the numbers of patients treated
      and the completeness of their followup, their clinical outcomes, and the setting
      in which their care was delivered. Choosing measures and methods for clinical
      outcome research to produce meaningful information that may be used to improve
      patient care presents a number of challenges. WHERE ARE WE NOW?: Orthopaedic
      surgery research has many stakeholders, including patients, providers, payers,
      and policy makers. A major challenge in orthopaedic surgery outcome measurement
      and clinical research is providing all of these users with valid information for
      their respective decision making. At present, no plan exists for capturing data
      on such a broad scale and scope. WHERE DO WE NEED TO GO?: Practical challenges
      include identifying and obtaining resources for widespread data collection and
      merging multiple data sources. Challenges of study design include sampling to
      obtain representative data, timing of data collection in the episode of care, and
      minimizing missing data and study dropout. HOW DO WE GET THERE?: Resource
      limitations may be addressed by repurposing existing clinical resources and
      capitalizing on technologic advances to increase efficiencies. Increasing use of
      rigorous, well-designed observational research designs can provide information
      that may be unattainable in clinical trials. Such study designs should
      incorporate methods to minimize missing data, to sample multiple providers,
      facilities, and patients, and to include evaluation of potential confounding
      variables to minimize bias and allow generalization to broad populations.

PMID- 23884807
TI  - Brain. Editorial.

PMID- 23884808
TI  - One complex world of mitochondrial parkinsonism.

PMID- 23884809
TI  - Accumulation of mitochondrial DNA deletions within dopaminergic neurons triggers
      neuroprotective mechanisms.
AB  - Acquired alterations in mitochondrial DNA are believed to play a pathogenic role
      in Parkinson's disease. In particular, accumulation of mitochondrial DNA
      deletions has been observed in substantia nigra pars compacta dopaminergic
      neurons from patients with Parkinson's disease and aged individuals. Also,
      mutations in mitochondrial DNA polymerase gamma result in multiple mitochondrial
      DNA deletions that can be associated with levodopa-responsive parkinsonism and
      severe substantia nigra pars compacta dopaminergic neurodegeneration. However,
      whether mitochondrial DNA deletions play a causative role in the demise of
      dopaminergic neurons remains unknown. Here we assessed the potential pathogenic
      effects of mitochondrial DNA deletions on the dopaminergic nigrostriatal system
      by using mutant mice possessing a proofreading-deficient form of mitochondrial
      DNA polymerase gamma (POLGD257A), which results in a time-dependent accumulation
      of mitochondrial DNA deletions in several tissues, including the brain. In these
      animals, we assessed the occurrence of mitochondrial DNA deletions within
      individual substantia nigra pars compacta dopaminergic neurons, by laser capture
      microdissection and quantitative real-time polymerase chain reaction, and
      determined the potential deleterious effects of such mitochondrial DNA
      alterations on mitochondrial function and dopaminergic neuronal integrity, by
      cytochrome c oxidase histochemistry and quantitative morphology. Nigral
      dopaminergic neurons from POLGD257A mice accumulate mitochondrial DNA deletions
      to a similar extent (~40-60%) as patients with Parkinson's disease and aged
      individuals. Despite such high levels of mitochondrial DNA deletions, the
      majority of substantia nigra pars compacta dopaminergic neurons from these
      animals did not exhibit mitochondrial dysfunction or degeneration. Only a few
      individual substantia nigra pars compacta neurons appeared as cytochrome c
      oxidase-negative, which exhibited higher levels of mitochondrial DNA deletions
      than cytochrome c oxidase-positive cells (60.38+/-3.92% versus 45.18+/-2.83%).
      Survival of dopaminergic neurons in POLGD257A mice was associated with increased
      mitochondrial DNA copy number, enhanced mitochondrial cristae network, improved
      mitochondrial respiration, decreased exacerbation of mitochondria-derived
      reactive oxygen species, greater striatal dopamine levels and resistance to
      parkinsonian mitochondrial neurotoxins. These results indicate that primary
      accumulation of mitochondrial DNA deletions within substantia nigra pars compacta
      dopaminergic neurons, at an extent similar to that observed in patients with
      Parkinson's disease, do not kill dopaminergic neurons but trigger neuroprotective
      compensatory mechanisms at a mitochondrial level that may account for the high
      pathogenic threshold of mitochondrial DNA deletions in these cells.

PMID- 23884810
TI  - Disease duration and the integrity of the nigrostriatal system in Parkinson's
      disease.
AB  - The pace of nigrostriatal degeneration, both with regards to striatal denervation
      and loss of melanin and tyrosine hydroxylase-positive neurons, is poorly
      understood especially early in the Parkinson's disease process. This study
      investigated the extent of nigrostriatal degeneration in patients with
      Parkinson's disease at different disease durations from time of diagnosis. Brains
      of patients with Parkinson's disease (n=28) with post-diagnostic intervals of 1
      27 years and normal elderly control subjects (n=9) were examined. Sections of the
      post-commissural putamen and substantia nigra pars compacta were processed for
      tyrosine hydroxylase and dopamine transporter immunohistochemistry. The post
      commissural putamen was selected due to tissue availability and the fact that
      dopamine loss in this region is associated with motor disability in Parkinson's
      disease. Quantitative assessments of putaminal dopaminergic fibre density and
      stereological estimates of the number of melanin-containing and tyrosine
      hydroxylase-immunoreactive neurons in the substantia nigra pars compacta (both in
      total and in subregions) were performed by blinded investigators in cases where
      suitable material was available (n=17). Dopaminergic markers in the dorsal
      putamen showed a modest loss at 1 year after diagnosis in the single case
      available for study. There was variable (moderate to marked) loss, at 3 years. At
      4 years post-diagnosis and thereafter, there was virtually complete loss of
      staining in the dorsal putamen with only an occasional abnormal dopaminergic
      fibre detected. In the substantia nigra pars compacta, there was a 50-90% loss of
      tyrosine hydroxylase-positive neurons from the earliest time points studied with
      only marginal additional loss thereafter. There was only a ~10% loss of melanized
      neurons in the one case evaluated 1 year post-diagnosis, and variable (30 to 60%)
      loss during the first several years post-diagnosis with more gradual and subtle
      loss in the second decade. At all time points, there were more melanin-containing
      than tyrosine hydroxylase-positive cells. Loss of dopaminergic markers in the
      dorsal putamen occurs rapidly and is virtually complete by 4 years post
      diagnosis. Loss of melanized nigral neurons lags behind the loss of dopamine
      markers. These findings have important implications for understanding the nature
      of Parkinson's disease neurodegeneration and for studies of putative
      neuroprotective/restorative therapies.

PMID- 23884811
TI  - Increased risk of narcolepsy in children and adults after pandemic H1N1
      vaccination in France.
AB  - An increased incidence of narcolepsy in children was detected in Scandinavian
      countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A
      campaign of vaccination against pandemic H1N1 influenza was implemented in France
      using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study
      considering all-type narcolepsy, we investigated the association between H1N1
      vaccination and narcolepsy with cataplexy in children and adults compared with
      matched controls; and compared the phenotype of narcolepsy with cataplexy
      according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy
      were included from 14 expert centres in France. Date of diagnosis constituted the
      index date. Validation of cases was performed by independent experts using the
      Brighton collaboration criteria. Up to four controls were individually matched to
      cases according to age, gender and geographic location. A structured telephone
      interview was performed to collect information on medical history, past
      infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were
      included; 23 being further excluded regarding eligibility criteria. Of the 62
      eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control
      subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds
      ratio of 6.5 (2.1-19.9) in subjects aged<18 years, and 4.7 (1.6-13.9) in those
      aged 18 and over. Sensitivity analyses considering date of referral for diagnosis
      or the date of onset of symptoms as the index date gave similar results, as did
      analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences
      were found when comparing cases with narcolepsy-cataplexy exposed to H1N1
      vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases
      (n=30), including shorter delay of diagnosis and a higher number of sleep onset
      rapid eye movement periods for exposed cases. No difference was found regarding
      history of infections. In this sub-analysis, H1N1 vaccination was strongly
      associated with an increased risk of narcolepsy-cataplexy in both children and
      adults in France. Even if, as in every observational study, the possibility that
      some biases participated in the association cannot be completely ruled out, the
      associations appeared robust to sensitivity analyses, and a specific analysis
      focusing on ASO3-adjuvanted vaccine found similar increase.

PMID- 23884812
TI  - Reduced spontaneous but relatively normal deliberate vicarious representations in
      psychopathy.
AB  - Psychopathy is a personality disorder associated with a profound lack of empathy.
      Neuroscientists have associated empathy and its interindividual variation with
      how strongly participants activate brain regions involved in their own actions,
      emotions and sensations while viewing those of others. Here we compared brain
      activity of 18 psychopathic offenders with 26 control subjects while viewing
      video clips of emotional hand interactions and while experiencing similar
      interactions. Brain regions involved in experiencing these interactions were not
      spontaneously activated as strongly in the patient group while viewing the video
      clips. However, this group difference was markedly reduced when we specifically
      instructed participants to feel with the actors in the videos. Our results
      suggest that psychopathy is not a simple incapacity for vicarious activations but
      rather reduced spontaneous vicarious activations co-existing with relatively
      normal deliberate counterparts. 

PMID- 23884813
TI  - Clinicopathological features of neuropathy associated with lymphoma.
AB  - Lymphoma causes various neurological manifestations that might affect any part of
      the nervous system and occur at any stage of the disease. The peripheral nervous
      system is one of the major constituents of the neurological involvement of
      lymphoma. In this study we characterized the clinical, electrophysiological and
      histopathological features of 32 patients with neuropathy associated with non
      Hodgkin's lymphoma that were unrelated to complications resulting from treatment
      for lymphoma. Nine patients had pathologically-proven neurolymphomatosis with
      direct invasion of lymphoma cells into the peripheral nervous system. These
      patients showed lymphomatous cell invasion that was more prominent in the
      proximal portions of the nerve trunk and that induced demyelination without
      macrophage invasion and subsequent axonal degeneration in the portion distal from
      the demyelination site. Six other patients were also considered to have
      neurolymphomatosis because these patients showed positive signals along the
      peripheral nerve on fluorodeoxyglucose positron emission tomography imaging.
      Spontaneous pain can significantly disrupt daily activities, as frequently
      reported in patients diagnosed with neurolymphomatosis. In contrast, five
      patients were considered to have paraneoplastic neuropathy because primary
      peripheral nerve lesions were observed without the invasion of lymphomatous
      cells, with three patients showing features compatible with chronic inflammatory
      demyelinating polyneuropathy, one patient showing sensory ganglionopathy, and one
      patient showing vasculitic neuropathy. Of the other 12 patients, 10 presented
      with multiple mononeuropathies. These patients showed clinical and
      electrophysiological features similar to those of neurolymphomatosis rather than
      paraneoplastic neuropathy. Electrophysiological findings suggestive of
      demyelination were frequently observed, even in patients with neurolymphomatosis.
      Eleven of the 32 patients, including five patients with neurolymphomatosis,
      fulfilled the European Federation of Neurological Societies/Peripheral Nerve
      Society electrodiagnostic criteria of definite chronic inflammatory demyelinating
      polyneuropathy. Some of these patients, even those with neurolymphomatosis,
      responded initially to immunomodulatory treatments, including the administration
      of intravenous immunoglobulin and steroids. Patients with lymphoma exhibit
      various neuropathic patterns, but neurolymphomatosis is the major cause of
      neuropathy. Misdiagnoses of neurolymphomatosis as chronic inflammatory
      demyelinating polyneuropathy are frequent due to a presence of a demyelinating
      pattern and the initial response to immunomodulatory treatments. The possibility
      of the concomitance of lymphoma should be considered in various types of
      neuropathy, even if the diagnostic criteria of chronic inflammatory demyelinating
      polyneuropathy are met, particularly in patients complaining of pain. 

PMID- 23884815
TI  - Selective imitation impairments differentially interact with language processing.
AB  - Whether motor and linguistic representations of actions share common neural
      structures has recently been the focus of an animated debate in cognitive
      neuroscience. Group studies with brain-damaged patients reported association
      patterns of praxic and linguistic deficits whereas single case studies documented
      double dissociations between the correct execution of gestures and their
      comprehension in verbal contexts. When the relationship between language and
      imitation was investigated, each ability was analysed as a unique process without
      distinguishing between possible subprocesses. However, recent cognitive models
      can be successfully used to account for these inconsistencies in the extant
      literature. In the present study, in 57 patients with left brain damage, we
      tested whether a deficit at imitating either meaningful or meaningless gestures
      differentially impinges on three distinct linguistic abilities (comprehension,
      naming and repetition). Based on the dual-pathway models, we predicted that
      praxic and linguistic performance would be associated when meaningful gestures
      are processed, and would dissociate for meaningless gestures. We used partial
      correlations to assess the association between patients' scores while accounting
      for potential confounding effects of aspecific factors such age, education and
      lesion size. We found that imitation of meaningful gestures significantly
      correlated with patients' performance on naming and repetition (but not on
      comprehension). This was not the case for the imitation of meaningless gestures.
      Moreover, voxel-based lesion-symptom mapping analysis revealed that damage to the
      angular gyrus specifically affected imitation of meaningless gestures,
      independent of patients' performance on linguistic tests. Instead, damage to the
      supramarginal gyrus affected not only imitation of meaningful gestures, but also
      patients' performance on naming and repetition. Our findings clarify the apparent
      conflict between associations and dissociations patterns previously observed in
      neuropsychological studies, and suggest that motor experience and language can
      interact when the two domains conceptually overlap. 

PMID- 23884814
TI  - Reading therapy strengthens top-down connectivity in patients with pure alexia.
AB  - This study tested the efficacy of audio-visual reading training in nine patients
      with pure alexia, an acquired reading disorder caused by damage to the left
      ventral occipitotemporal cortex. As well as testing the therapy's impact on
      reading speed, we investigated the functional reorganization underlying therapy
      induced behavioural changes using magnetoencephalography. Reading ability was
      tested twice before training (t1 and t2) and twice after completion of the 6-week
      training period (t3 and t4). At t3 there was a significant improvement in word
      reading speed and reduction of the word length effect for trained words only.
      Magnetoencephalography at t3 demonstrated significant differences in reading
      network connectivity for trained and untrained words. The training effects were
      supported by increased bidirectional connectivity between the left occipital and
      ventral occipitotemporal perilesional cortex, and increased feedback connectivity
      from the left inferior frontal gyrus. Conversely, connection strengths between
      right hemisphere regions became weaker after training. 

PMID- 23884816
TI  - The optimal management of follicular lymphoma: an evolving field.
AB  - Follicular lymphoma consists of a heterogeneous group of diseases that can vary
      dramatically in clinical course. As with other indolent lymphomas, follicular
      lymphoma is felt to be highly treatable, but ultimately incurable. The
      appropriate management of this disease ranges from close observation to
      chemoimmunotherapy based on presenting symptoms and comorbidities. In this
      article, we focus on the optimal management of follicular lymphoma, including
      prognostication, indications for treatment, and current treatment options. While
      a number of front-line chemoimmunotherapy options exist, R-CHOP (rituximab,
      cyclophosphamide, vincristine, prednisone) and BR (bendamustine, rituximab) tend
      to be favored due to efficacy and tolerability. Post-induction options include
      maintenance rituximab and radioimmunotherapy, but neither has demonstrated an
      overall survival benefit. In relapsed disease, patients can receive an
      alternative chemoimmunotherapy regimen or radioimmunotherapy, or participate in a
      clinical trial. There are a number of new biologic targeted therapies with
      promising activity in follicular lymphoma that have the potential to change our
      approach to this disease. 

PMID- 23884818
TI  - Comparative antioxidant activity of cultivated and wild Vaccinium species
      investigated by EPR, human neutrophil burst and COMET assay.
AB  - OBJECTIVES: The Vaccinium (V.) spp. berries are considered a source of
      antioxidants, mainly belonging to polyphenols, specifically flavonoids and
      anthocyanins. Wild genotypes generally contain more antioxidants than cultivated
      counterparts. So, seven different antioxidants assays on extracts from cultivated
      and wild Vaccinium berries were performed, to evaluate their difference in terms
      of bioactivity on oxidative protection and minimum dosage to have a significant
      action. MATERIALS AND METHODS: Four cell-free antioxidant assays (ABTS radical
      scavenging and electronic paramagnetic resonance using Fremy's salt, superoxide
      anion and hydroxyl radical), and three assays on human cells (two luminol
      amplified chemiluminescence, LACL, one on DNA damage, COMET) were used to measure
      the effects of cultivated blueberry (V. corymbosum) and wild bilberry (V.
      myrtillus) on the differently induced oxidative stress. Concentrations vs
      activity patterns were obtained by successive dilutions of extracts in order to
      identify both EC50 and minimum significant activity (MSA). RESULTS: All the
      assays (except for the hydroxyl radical scavenging) showed a good relationship
      mainly with anthocyanin and polyphenol content and the significant greater
      activity of wild Vaccinium extracts. In fact, LACL data gave an EC50 of 11.8 and
      an MSA of 5.2 g were calculated as fresh weight dosage in cultivated berries,
      compared with lower doses in wild berries, EC50 of 5.7 g and MSA of 3.4 g.
      CONCLUSIONS: Wild Vaccinium extracts averaged 3.04 and 2.40 fold more activity
      than cultivated extracts by EC50 and MSA, respectively. COMET assay confirmed the
      stronger action on DNA protection in wild samples.

PMID- 23884819
TI  - 15-PGDH inhibitors: the antiulcer effects of carbenoxolone, pioglitazone and
      verapamil in indomethacin induced peptic ulcer rats.
AB  - BACKGROUND AND AIM: 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the enzyme
      responsible for prostaglandins (PGs) metabolism. PGs have an important role in
      the protection of stomach mucosa against destructive stimuli. The aim of the
      present study is to investigate the inhibitory effect of carbenoxolone,
      pioglitazone and verapamil on 15-PGDH enzyme. MATERIALS AND METHODS: The
      experiments were carried out in the Faculty of Pharmacy, Suez Canal University,
      Ismailia, Egypt from May 2011 to August 2011. Adult male albino rats were fasted
      for 18 hours before administration of high dose of indomethacin (30 mg/kg, p.o.),
      except for the negative control group which received saline only, followed by
      pyloric ligation to induce acute gastric ulcers. The rats were pretreated orally
      with saline, pioglitazone (20 mg/kg), verapamil (25 mg/kg), carbenoxolone (30
      mg/kg) or their combinations 30 minutes before indomethacin. The rats were
      sacrificed after four hours of pyloric ligation. The effects of the previous
      treatments on the ulcer index (Ui), the microscopic appearance of gastric mucosa,
      the gastric acid output, the gastric barrier mucus content, and 15-PGDH enzyme
      activity were determined. RESULTS: Indomethacin resulted in severe ulceration and
      increased gastric acid output (p < 0.05) compared to negative control. The rats
      pretreated with carbenoxolone, pioglitazone, verapamil had reduced ulcer index,
      gastric acid output and 15-PGDH activity (p < 0.05) compared to either
      indomethacin group or the negative control group. Individual treatments with
      carbenoxolone, pioglitazone or verapamil increased gastric barrier mucus (p <
      0.05) compared to either indomethacin group or the negative control group. The
      combinations of verapamil with either carbenoxolone or pioglitazone caused
      further reduction in ulcer index, gastric acid output and 15-PGDH activity (p <
      0.05), while causing further increase in gastric barrier mucus (p < 0.05)
      compared to their respective individual treatment group. CONCLUSIONS: The
      antiulcer properties of pioglitazone and verapamil are, in part, consequences of
      their inhibitory effect on the enzyme 15-PGDH, responsible for PGs degradation,
      and the resultant prolongation of PGE2 biological activity in rat stomach mucosa.

PMID- 23884820
TI  - Effect of HMGB1/NF-kappaB in hyperbaric oxygen treatment on decreasing injury
      caused by skin flap grafts in rats.
AB  - BACKGROUND: Skin flap grafting (SFG) is a common surgical operation, and
      hyperbaric oxygen treatment (HBOT) is an important strategy for restoring the
      grafted skin flap. Thus, we employed a rat skin flap grafting model treated with
      HBO, and expression levels of high mobility group protein 1 (HMGB1) and NF-kappaB
      (nuclear factor-kappaB) were characterized. MATERIALS AND METHODS: Forty rats
      were randomly assigned to 5 groups: (1) sham-operation (SH), (2) ischemia
      followed by reperfusion 3 days after operation (IR3d), (3) ischemia followed by
      reperfusion 5 days after operation (IR5d), (4) ischemia followed by reperfusion
      and HBOT 3 days after operation (HBO3d), and (5) ischemia followed by reperfusion
      and HBOT 5 days after operation (HBO5d). Elevated pedicled skin flaps were
      designed (size, 9 cm * 6 cm), and feeding vessels were clamped. The microvascular
      clamp was removed 3 h later and flow was restored. In the HBO3d and HBO5d groups,
      rats received 1 h of hyperbaric oxygen (HBO) starting immediately after surgery
      for 3 days and 5 days, respectively. Upon completion of animal experiments, rats
      were euthanized by general anesthesia, and blood samples were taken for testing.
      The tissues were sectioned for western blotting and immunohistochemical staining.
      RESULTS: Expression of HMGB1 and NF-kappaB proteins in the HBO groups was lower
      than in the IR groups. CONCLUSIONS: The results suggest that HBOT can be used to
      reduce ischemia-reperfusion (IR) injury of skin flap grafts.

PMID- 23884821
TI  - Involvement of monoaminergic system in the antidepressant-like effect of aqueous
      extract of Channa striatus in mice.
AB  - BACKGROUND: In our previous study, the aqueous extract of Channa striatus
      (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice.
      However, the mechanism of the antidepressant-like effect is unknown. AIM: The
      objective of this study was to explore the involvement of monoamines in the
      antidepressant-like effect of AECSF in mice. MATERIALS AND METHODS: AECSF was
      prepared by steaming the fillets of C. striatus. The male ICR mice were
      pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine
      (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.),
      SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment
      with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey
      test were used at p < 0.05 for significance. RESULTS: The pretreatments with p
      chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride,
      were able to reverse the antidepressant-like effect of AECSF in TST. CONCLUSIONS:
      The antidepressant-like effect of AECSF may be mediated through the serotonergic
      and noradrenergic systems and not through the dopaminergic system.

PMID- 23884822
TI  - The current status of combination therapy of chronic hepatitis B.
AB  - In the past decade, the treatment of chronic Hepatitis B (CHB) has been
      revolutionized by the increased availability of effective antiviral agents.
      However, there is an alarming of the increasing rates of viral resistance and
      suboptimal response in CHB patients with single drug therapy. Recently, the
      strategy of combination therapy for CHB has been proposed and concerned by
      clinicians. In this review, using PubMed and web of science as main searching
      tools, we evaluated various latest research reports on combination therapy for
      CHB, and made a summary of the progress of combination antiviral therapy and
      outline areas that need to be addressed in the future. 

PMID- 23884823
TI  - Determination and clinical correlation of markers of inflammation in unvaccinated
      patients with varicella-zoster infection.
AB  - BACKGROUND: Chicken pox is commonly known as a benign exenthamatous disease of
      childhood, occasionally neurologic or hemorrhagic complications, or even death
      may ensue. Early predictors of severity of disease have yet to be identified. TNF
      alpha and IL-6 stimulate virus-specific immunoglobulin production and it has been
      postulated that determination of levels of these cytokines may be useful as a
      prognostic factor. PATIENTS AND METHODS: Patients who were diagnosed with a
      varicella-zoster virus (VZV) infection in the Outpatient Clinic of the Department
      of Pediatric Infectious Diseases were evaluated for eligibility. Laboratory
      assays included an evaluation of complete blood counts, erythrocyte-sedimentation
      rate (ESR), c reactive protein (CRP), and the number of tumor necrosis factor
      alpha/interleukin-6-(TNF-alpha/IL-6-) producing mononuclear cells as determined
      by flow cytometry. RESULTS: A total of 339 patients (320 with chickenpox and 19
      with shingles) were enrolled. Blood samples could only be obtained from 81 of the
      320 patients with chickenpox. Patients were also divided into three groups
      depending on the number of skin (vesicular) lesions. (group 1, <= 50 lesions;
      group 2, 51-100 lesions; group 3, >100 lesions). Correlation analyses did not
      reveal the presence of a statistically significant correlation between number of
      skin lesions with either of white blood cells (WBC) count (p = 0.231), ESR (p =
      0.879) or CRP (p = 0.373). The mean percentage of TNF-alpha-producing mononuclear
      cells was significantly higher in group 2 compared to group 3 (p = 0.003). A
      similar difference was observed with regard to IL-6-producing mononuclear cells,
      albeit bordering on statistical significance (p = 0.058). CONCLUSIONS: Decreased
      expression of the cytokines TNF-alpha and IL-6 may be responsible for the
      development of a more severe clinical picture in patients with VZV infection, and
      determination of intracellular levels of these cytokines may be of benefit for
      early identification of patients who may have a more severe clinical course.

PMID- 23884824
TI  - High prevalence of undiagnosed anxiety symptoms among HIV-positive individuals on
      cART: a cross-sectional study.
AB  - INTRODUCTION: Anxiety disorders are frequent in HIV-infected individuals, can pre
      exist or occur during HIV infection. We evaluated with a self-reported
      questionnaire whether anxiety is related to HIV clinical status and therapeutic
      success in a cohort of HIV-positive subjects in Sicily. PATIENTS AND METHODS: We
      enrolled 251 patients on combination antiretroviral therapy (cART) for at least
      six months; Self Rating Anxiety State SAS 054 was used to diagnose anxiety and a
      Z score >= 45 points was considered diagnostic. RESULTS: 47% of patients were
      diagnosed with anxiety. Patients showing symptoms related to anxiety had
      experienced a high number of therapeutic switches (fourth line or more).
      CONCLUSIONS: These data confirm a high prevalence of anxiety symptoms among
      subjects with HIV infection in Eastern Sicily. Physicians should be aware of the
      extent of the problem and should be able to adequately manage anxiety in the
      setting of HIV infection.

PMID- 23884825
TI  - Anti-giardial activity of Sambucus ebulus.
AB  - OBJECTIVES: Giardia (G.) lamblia is a parasite that causes giardiasis in humans
      and other mammals. The common treatment produces unpleasant side effects. The
      ethnopharmacology for management of parasitic infections accelerates and guides
      the search for new chemical objects. This study assessed the in vitro
      cytotoxicity of Sambucus (S.) ebulus fruit against Cysts of G. lamblia. MATERIALS
      AND METHODS: Giardia cysts were isolated from patients' fecal specimens; the
      cysts were isolated by sucrose 0.85 M solution. The plant extract was used at
      concentrations of 1, 10, 50 and 100 mg/mL throughout the experiments. The
      extracts were incubated with several isolates of G. lamblia for 5, 10, 30 and 60
      minutes and then the viability were distinguished by eosin 0.01%. RESULTS: S.
      ebulus extract at the concentration of 100 mg/ml for 60 minutes had the most anti
      giardial activity (78 +/- 4%) than other concentrations. CONCLUSIONS: Considering
      excellent antigiardial activity of S. ebulus in vitro, it seems to have potential
      for the treatment of the parasitic disease caused by the protozoan G. lamblia.

PMID- 23884826
TI  - The effects of ephedrine on maternal hypothermia in caesarean sections: a double
      blind randomized clinical trial.
AB  - BACKGROUND: The purpose of the study was to investigate the effect of bolus and
      the combination of bolus and infusion of ephedrine on maternal hypothermia which
      are used for treating maternal hypotension under spinal anaesthesia. PATIENTS AND
      METHODS: 110 ASA I-II patients who developed maternal hypotension were included
      into the study. Spinal anaesthesia was performed with 12.5 mg heavy bupivacaine +
      15 ug fentanyl. Group I: Ephedrine bolus 5 mg plus ephedrine infusion, Group B:
      Ephedrine bolus 5 mg plus normal saline infusion. The systolic blood pressure was
      allowed to range between 20% from baseline values. Ephedrine solution infusion
      started after hypotension occurred (0.5 mg/minute). The body temperature under
      35.5 degrees C was accepted as hypothermia. The newborns' rectal temperature was
      measured. Moreover, the Apgar scores, umbilical vein-arterial blood gas and acid
      base status were evaluated. RESULTS: In Group I, the body core temperatures which
      were measured at 9, 18, 33, and 39th minutes were significantly higher than Group
      B (p < 0.05). The prevalence of maternal hypothermia in Group I was significantly
      lower than the Group B, which were as 65.5% (36/55) and 85.5% (47/55),
      respectively (p < 0.05). In Group I, the newborn rectal temperatures and the
      total dose of ephedrine were significantly higher than Group B (p < 0.05). In
      Group I, the systolic and mean blood pressures were higher than Group B (p <
      0.05). CONCLUSIONS: As a result, we found that combined bolus and infusion of
      ephedrine for treating maternal hypotension prevents maternal and neonatal
      hypothermia during caesarean section under spinal anaesthesia compared to bolus
      administrations alone.

PMID- 23884827
TI  - Role of insulin resistance and adipocytokines on serum alanine aminotransferase
      in obese patients with type 2 diabetes mellitus.
AB  - BACKGROUND AND OBJECTIVE: The aim of our study was to study the association of
      insulin resistance expressed by HOMA and adipokines in obese type 2 diabetic
      patients with or without hyper-transaminasemia. SUBJECTS AND METHODS: A
      population of 72 obese patients with type 2 diabetes mellitus was analyzed. HOMA
      IR was calculated as indicator of insulin-resistance. Adipocytokines blood levels
      were measured. RESULTS: Patients were classified as group I (n=37) when serum ALT
      activity was normal or group II (NAFLD patients: n=35) when serum ALT activity
      was greater than the median value of the group (>= 28 UI/L). In NAFLD group, BMI,
      weight, fat mass, waist to hip ratio, waist circumference, triglycerides, HOMA
      and insulin levels were higher than control group. In the logistic regression
      analysis with a dependent variable (ALT) and the statistical univariant variables
      as independent variables, the HOMA-IR remained in the model, with an Odd's ratio
      of 1.21 (CI:95%: 1.11-1.35) to have a high ALT level with each 1 unit of HOMA-IR
      adjusted by age, sex, weight, and dietary intake. CONCLUSIONS: Some metabolic
      parameters are associated with elevated ALT in female obese patients. However,
      adjusted by other variables, only insulin resistance remained associated.

PMID- 23884828
TI  - Do Akiskal & Mallya's affective temperaments belong to the domain of pathology or
      to that of normality?
AB  - BACKGROUND: Kraepelin and Kretschmer hypothesized a continuum between full-blown
      affective pathology and premorbid temperaments. More recently Akiskal proposed a
      putative adaptive role for the four fundamental temperaments: the hyperthymic one
      characterized by emotional intensity, the cyclothymic one by emotional
      instability, the depressive one by a low energy level, and the irritable one by
      an excessive response to stimuli. Today it is widely debated whether affective
      temperaments belong to the domain of pathology or to that of normality. PURPOSE:
      To make clear, by applying an integrated model, the position of affective
      temperaments within the continuum between normality and pathology. METHODS: We
      reviewed several papers that explore the distribution of affective temperaments
      among the general population, and their involvement both in pathological
      conditions (somatic and psychiatric) and in human activities (professions and
      other occupations). RESULTS: Far from being intrinsically pathological
      conditions, affective temperaments seem to represent adaptive dispositions whose
      dysregulation can lead to full-blown affective pathology. All the temperamental
      types display some impact on people's lives by influencing personal skills and
      professional choices over a wide field of human activities. CONCLUSIONS:
      Affective temperaments are not problematic when they appear in a mild form, but
      when they occur in extreme form we have observed a gap between the hyperthymic
      temperament, which represents the most functional and desirable, and the
      cyclothymic, depressive, irritable and phobic anxious ones, which are closer to
      mood, anxiety, and substance use disorders, and imply a component of somatic
      diseases and life stressors.

PMID- 23884829
TI  - Effects of melatonin on behavioral changes of neonatal rats in a model of
      cortical dysplasia.
AB  - BACKGROUND: Cortical dysplasia (CD) is associated with several behavioral
      disorders in both the pediatric and the adult population. The effect of melatonin
      on behavioral disorders in rats generated CD has not been investigated so far.
      AIM: To investigate the effects of melatonin administration on activity and
      anxietic behavior of neonatal rats in a model of CD. MATERIALS AND METHODS:
      Newborn Sprague-Dawley rats (n=21) were randomized into three groups. On
      postnatal day 1, one freeze lesion was carried out in 14 rats between bregma and
      lambda to create a CD model. Another group of neonatal rats served as control
      group (n=7). Those 14 rats were either administered melatonin (n=7) or vehicle
      solution (n=7). Melatonin treatment (4 mg/kg/day, i.p.) was initiated ten days
      after induction of cold injury and continued for three weeks. Animal activity and
      anxiety were analyzed by using open field and elevated plus maze tests 24h after
      the last melatonin administration (day 32) in a blind manner. RESULTS: It was
      observed that CD induced animals spent significantly less time in the open field
      area when compared to the other groups (p < 0.01). Additionally, the time spent
      in the open field area was significantly elevated in the melatonin-treated
      animals compared to both the control and the CD groups (p < 0.01). Accordingly,
      anxiety scores in the CD group was significantly increased (p < 0.01), and this
      effect could be reversed by administration of melatonin. CONCLUSIONS: Melatonin
      exerts protective behavioral effects against cortical dysplasia in newborn rats.
      Further clinical investigations may prove melatonin as a useful therapeutic
      adjunct to prevent from possible behavioural damages of cortical dysplasia.

PMID- 23884830
TI  - Effect of an extra-virgin olive oil enriched with probiotics or antioxidants on
      functional dyspepsia: a pilot study.
AB  - BACKGROUND: While antioxidants and probiotics have been proposed for the
      treatment of functional dyspepsia, current data are still heterogeneous and
      studies are poorly designed. Extra-virgin olive oil, a common ingredient of
      Mediterranean diet, has shown antioxidant properties. AIMS: To evaluate the
      effect of extra-virgin olive oil enriched with antioxidants or probiotics on
      functional dyspepsia. PATIENTS AND METHODS: This study has been designed as a
      "proof of concept". Extra-virgin olive oil enriched with antioxidants or
      probiotics was blindly added to the common diet of 8 subjects with functional
      dyspepsia for 7 days. Dyspeptic symptoms were then evaluated in all patients.
      RESULTS AND CONCLUSIONS: A significant improvement of dyspeptic symptoms was
      observed in subjects receiving the antioxidant or probiotic enriched oil diet,
      with a greater effect observed for the latter. Larger studies are now needed to
      confirm these data.

PMID- 23884831
TI  - Establishing a combined stimulation protocol hFSH followed by rFSH might
      represent a breakthrough in the IVF practice.
AB  - INTRODUCTION: Controlled ovarian stimulation directly influences assisted
      reproductive technology (ART) outcomes. Indeed, several studies have shown that
      the total IU of gonadotropins used for ovarian stimulation inversely correlates
      with pregnancy rate. Nowadays, two main gonadotropins are used in ART protocols,
      human-derived and recombinant follicle-stimulating hormone (FSH). The difference
      between these two hormones is dramatic. Indeed, the human-derived FSH is an
      acidic isoform of the hormone while the recombinant is a less acid one. In
      particular, during a physiological menstrual cycle the acid isoform is produced
      during the follicular phase (probably it is more effective in recruiting
      follicles) while less acidic isoform is produced during the mid follicular phase
      (preovulatory). In the present study, we aim to evaluate the efficacy of a
      protocol that mimics the physiological shift form an acidic to a less acid FSH
      isoform during oocyte maturation. PATIENTS AND METHODS: A total of 308 infertile
      couples undergoing their first Intracytoplasmic Sperm Injection (ICSI) treatment
      were enrolled. All patients underwent a standard down-regulation protocol with
      GnRH analogue hormone. Patients were randomized in two groups: group 1, patients
      that received 225 IU of human-derived FSH (hFSH Fostimon, IBSA, Lodi, Italy) for
      6 days from the second day of the cycle and then 225 IU of recombinant FSH (rFSH
      Gonal-F; Serono, Rome, Italy) from the 7th day of stimulation until hCG
      administration, and group 2, control group, patients that received 225 IU
      recombinant FSH alone from the second day of the cycle until hCG administration.
      RESULTS: The combined protocol (hFSH + rFSH) resulted in significantly less IU of
      FSH necessary for ovarian stimulation together with the stimulation days.
      Furthermore, oocyte and embryo quality was higher in the group of patients
      treated with the combined protocol. Noteworthy, a significantly higher
      implantation rate and pregnancy rate were observed in favour of group 1 compared
      to group 2. CONCLUSIONS: We demonstrated that establishing a stimulation protocol
      able to mimic the physiological differences in FSH isoforms, hFSH combined with
      rFSH positively impact on ART outcome.

PMID- 23884832
TI  - Expression profiling based on graph-clustering approach to determine
      osteoarthritis related pathway.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common disease of joints in adults
      around the world. Current available drugs to treat osteoarthritis are
      predominantly directed towards the symptomatic relief of pain and inflammation
      but they do little to reduce joint destruction. Effective prevention of the
      structural damage must be a key objective of new therapeutic approaches.
      Therefore, it is worthwhile to search for important molecular markers that hold
      great promise for further treatment of patients with osteoarthritis. AIM: In this
      study, we used a graph-clustering approach to identify gene expression profiles
      that distinguish OA patients from normal samples. MATERIALS AND METHODS: We
      performed a comprehensive gene level assessment of osteoarthritis using five
      osteoarthritis samples and five normal samples graph-clustering approach.
      RESULTS: The results showed that TNFAIP3, ATF3, PPARG, etc, have related with
      osteoarthritis. Besides, we further mined the underlying molecular mechanism
      within these differently genes. CONCLUSIONS: The results indicated tyrosine
      metabolism pathway and cell cycle pathway were two significant pathways, and
      there was evident to demonstrate them based on previous reports. We hope to
      provide insights into the development of novel therapeutic targets and pathways.

PMID- 23884833
TI  - Effect of carvedilol on cardiac dysfunction 4 days after myocardial infarction in
      rats: role of toll-like receptor 4 and beta-arrestin 2.
AB  - OBJECTIVES: To assess the beneficial effect of carvedilol treatment on infarct
      myocardium and the relation to the expression of nuclear factor-kappa B (NF
      kappaB), Toll-like receptor 4 (TLR4), and beta-arrestin 2. MATERIALS AND METHODS:
      Rat myocardial infarction (MI) model was produced by ligating the left anterior
      descending coronary artery. Forty-eight rats were randomized to the following
      groups before surgery: sham-operated group (n=8), MI group (n=10), and three
      carvedilol-treatment groups (n=30, 2 mg/kg, 10 mg/kg and 30 mg/kg). RESULTS: Four
      days after MI, carvedilol treatment could ameliorate left ventricular dysfunction
      by inhibiting the MI-induced increase of left ventricular end diastolic pressure
      and the decrease of left ventricle end systolic pressure and the changes to their
      maximum rates (+dp/dtmax and -dp/dtmax). Histological examination showed that
      carvedilol attenuated myocardium necrosis and inflammatory cell infiltration. In
      parallel, the treatment also suppressed the expression of NF-kappaB and TLR4
      induced by MI, but increased the expression of beta-arrestin 2. CONCLUSIONS:
      These results indicate that short term administration of carvedilol could improve
      early cardiac dysfunction in a rat model of MI. This beneficial effect may be
      attributed to inhibit the expression of NF-kappaB and TLR4, but induce the
      expression of beta-arrestin 2 in the infarct region of the myocardium, which
      would suppress inflammation.

PMID- 23884834
TI  - Increased epicardial fat thickness is related with body mass index in women with
      polycystic ovary syndrome.
AB  - AIM: We aimed to investigate the relationship between PCOS and epicardial fat
      thickness with transthoracic echocardiography. PATIENTS AND METHODS: PCOS
      patients were divided into two groups according to the lean or obesity status:
      PCOS patients with lean 34 subjects (BMI: 23.3+/-2.8; mean age: 25.5+/-4), PCOS
      patients with obese16 subjects (BMI: 32.3+/-7.6; mean age: 27.2+/-3.7) were
      compared with control healthy lean subjects (BMI: 23.5+/-1.7; mean age: 25.9+/
      2.2). RESULTS: There was increased epicardial thickness in obese PCOS subjects
      compared to lean PCOS subjects (6.3+/-0.9 mm, 4.7+/-0.5, respectively, p <
      0.001). However, epicardial fat thickness between lean PCOS subjects and lean
      healthy control groups were not significantly varied (4.7+/-0.5 mm, 4.5+/-0.5,
      respectively, p = 0.6). There was increased epicardial thickness in obese PCOS
      subjects compared to lean healthy control subjects (6.3+/-0.9 mm, 4.5+/-0.5,
      respectively, p < 0.001). This sudy showed for the first time that increased
      epicardial fat thickness measured using transthoracic echocardiography is
      associated with increased BMI in PCOS subjects. CONCLUSIONS: Epicardial fat
      thickness between lean PCOS subjects and lean healty control group were similar
      which indicate the importance of obesity in PCOS subjects.

PMID- 23884835
TI  - Identification of microRNAs present in congenital heart disease associated copy
      number variants.
AB  - PURPOSE: Congenital heart disease (CHD) is the most common congenital anomaly in
      newborns and about 1.35 million infants are born with CHD each year worldwide.
      Recently a large category of copy number variants (CNVs), were established to be
      a major contributor of the pathophysiology of CHD. To date most studies focused
      on the analysis of CNV categories or the protein coding regions without
      investigation on the impact of non-coding regulatory microRNAs (miRNAs).
      MATERIALS AND METHODS: Here with an array comparative genome hybridisation data
      set and a gene expression profile data set, we investigated the contribution of
      miRNAs in CNVs towards the development of CHD. RESULTS: Approximately 18% of the
      identified high frequency CNV loci were shown to harbor miRNAs. According the
      expression profile analysis, 52 target genes of 16 miRNAs showed association with
      CHD. Targets of hsa-miR-650 was reported to be enriched with genes of cardiac
      dysfunctions and heart failure categories previously. In the constructed network,
      all 12 miRNAs directly or indirectly interacts with CHD related genes and hsa-miR
      570 showed the highest degree. CONCLUSIONS: Our study highlights the significance
      of CNV-microRNAs and their target genes in the pathogenesis of CHD. This
      knowledge will facilitate the identification of miRNA biomarkers and the
      development of new therapeutics for CHD.

PMID- 23884836
TI  - Association of serum paraoxonase activity and coronary artery calcification.
AB  - AIM: It has been known that there was a relation between the activities of serum
      paraoxonase (PON) and the severity of the coronary artery disease. However,
      little is known about association of coronary artery calcification (CAC) and
      serum PON activities. The aim of this study is to evaluate the relationship
      between CAC and serum PON activities. PATIENTS AND METHODS: We measure serum PON
      activities from 122 patients (42 female, mean age = 62+/-10 years) with
      angiographically documented CAC (Group I), and 138 patients (54 female, mean age
      = 60+/-10 years) without CAC (Group II). Coronary calcification was detected with
      fluoroscopy before coronary angiography. Serum PON activities were measured by
      spectrophotometrically method. Patient characteristics and baseline data were
      recorded from patient's files. RESULTS: The triglyceride levels is lower in group
      I than group II (p = 0.040). Diastolic blood pressure and frequency of diabetes
      mellitus was higher in the group I than group II (respectively p = 0.012 and p =
      0.022). The other clinic and laboratory parameters were similar in two groups
      (all p > 0.05). The only statistically significant differences between with CAC
      and without CAC groups in respect to serum PON activities were present (170.6 +/-
      59.6 vs. 209.6 +/- 69.8 U/ml; respectively, p < 0.001). There was a negative
      correlation between serum PON activities and presence of CAC (p < 0.001).
      CONCLUSIONS: These data indicate that the serum PON activities are decreased in
      patients with CAC. The serum PON activities may play a role in development of the
      CAC and reduced serum PON activity might represent a biochemical marker of CAC.

PMID- 23884837
TI  - Evaluation of platelet activation by platelet volume indices.

PMID- 23884838
TI  - MRI-guided stereotactic aspiration of brain abscesses by use of an optical
      tracking navigation system.
AB  - BACKGROUND: Owing to the high risk of abscess drainage by craniotomy, imaging
      guided stereotactic aspiration is considered an ideal choice in the management of
      brain abscesses. Interventional magnetic resonance imaging (MRI) represents a
      valuable technique for the treatment of brain abscess as a guiding modality.
      PURPOSE: To evaluate the safety and efficacy of an interventional MRI system in
      performing the procedure. MATERIAL AND METHODS: Thirteen brain abscesses in 11
      patients were treated with percutaneous aspiration. All procedures were performed
      solely under the guidance of a 0.23-T open-configuration MRI scanner with optical
      tracking. Clinical and imaging follow-up was at 1 week, 1 month, 3 months, and 6
      months. The changes of abscess, MRI features, and clinical symptoms were
      recorded. Procedure efficacy and safety were evaluated by success rate, procedure
      time, decrease of abscess, recovery rate, and complication. Descriptive
      statistical analysis was performed. RESULTS: MRI-guided stereotactic aspirations
      were performed successfully in 13/13 (100%) abscesses. The mean operating time
      was 70 min (range, 45-100 min). Follow-up MRI at 1 week after the procedure
      showed average reduction of abscesses by 60% (2.1/3.5). And the abscesses
      continued to get smaller by up to 89.7% (3.14/3.5) at 1-month follow-up. All
      cavities resolved at the end of the 6-month follow-up period. The recovery rate
      was 100% for fever, headache, vomiting, papilledema, meningismus, altered
      sensorium, 75% (3/4) for hemiparesis, and 83.3% (5/6) for epilepsy. There were no
      complications. CONCLUSION: Punctures of brain abscesses with subsequent
      aspiration can be performed safely and efficiently by monitoring the procedure
      using an open interventional MRI system.

PMID- 23884839
TI  - Radiation exposure of the radiologist's eye lens during CT-guided interventions.
AB  - BACKGROUND: In the past decade the number of computed tomography (CT)-guided
      procedures performed by interventional radiologists have increased, leading to a
      significantly higher radiation exposure of the interventionalist's eye lens.
      Because of growing concern that there is a stochastic effect for the development
      of lens opacification, eye lens dose reduction for operators and patients should
      be of maximal interest. PURPOSE: To determine the interventionalist's equivalent
      eye lens dose during CT-guided interventions and to relate the results to the
      maximum of the recommended equivalent dose limit. MATERIAL AND METHODS: During 89
      CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements
      of eye lens' radiation doses were obtained from a dedicated dosimeter system for
      scattered radiation. The sensor of the personal dosimeter system was clipped onto
      the side of the lead glasses which was located nearest to the CT gantry. After
      the procedure, radiation dose (uSv), dose rate (uSv/min) and the total exposure
      time (s) were recorded. RESULTS: For all 89 interventions, the median total
      exposure lens dose was 3.3 uSv (range, 0.03-218.9 uSv) for a median exposure time
      of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 uSv/min (range, 1.1
      335.5 uSv/min). CONCLUSION: Estimating 50-200 CT-guided interventions per year
      performed by one interventionalist, the median dose of the eye lens of the
      interventional radiologist does not exceed the maximum of the ICRP-recommended
      equivalent eye lens dose limit of 20 mSv per year.

PMID- 23884840
TI  - The clinical and CT imaging features of metanephric adenoma.
AB  - BACKGROUND: Patients with metanephric adenoma have a good prognosis after
      undergoing total nephrectomy or local resection with kidney preservation.
      Accurate diagnosing is important for guiding clinical treatment. Only few
      previous case reports have been found focusing on the imaging findings of
      metanephric adenoma. PURPOSE: To evaluate the multislice computed tomography
      (MSCT) imaging characteristics of metanephric adenoma. MATERIAL AND METHODS: The
      imaging findings in eight patients with metanephric adenoma were studied
      retrospectively. MSCT was undertaken to investigate tumor location, size,
      attenuation, cystic or solid appearance, calcification, capsule sign, and
      enhancement pattern. RESULTS: Tumors (mean diameter, 3.3 +/- 1.0 cm) were
      solitary (8/8), solid (7/8) with cystic components (2/8), no calcifications
      (7/8), had a poorly-defined margin (8/8), were centered in the renal medulla
      (7/8), compressed the renal pelvis (3/8), and none had retroperitoneal lymph node
      metastasis. The attenuation of metanephric adenoma tumors was less or equal
      compared to the renal cortex or medulla on unenhanced CT (30.6 +/- 2.6 vs. 36.3
      +/- 4.6 vs. 33.2 +/- 3.9, P > 0.05), while tumor enhancement after administration
      of an contrast agent was lower than that of normal renal cortex and medulla
      during all phases (P < 0.05). CONCLUSION: Metanephric adenoma tends to be a
      solitary, poorly defined margin, isodense or hypodense mass arising from the
      renal medulla with enhancement less than the cortex and medulla during all
      phases.

PMID- 23884841
TI  - PET/CT imaging of skeletal muscle metastases.
AB  - BACKGROUND: Skeletal muscle metastases (SMM) are very rare because of complex
      resistance of the musculature to metastatic invasion. Previously, positron
      emission tomography (PET) imaging of SMM has been reported only in few reports. A
      systematic analysis of SMM features in PET/CT has not been performed before.
      PURPOSE: To study PET/CT findings of SMM in a larger group of patients with known
      malignancies and to determine PET/CT patterns of SMM in different primary tumors.
      MATERIAL AND METHODS: Between January 2009 and December 2011 581 patients with
      lung cancer were investigated by PET with 18 F-fluordeoxyglucose (FDG PET) and
      computed tomography (CT) at the Center of Fusion Imaging, Halle. In five patients
      SMM were identified. Furthermore, PubMed database was screened for muscle
      metastases. Only articles containing SUV of SMM were considered in the study.
      Twenty-one articles with 33 patients could be included in this meta-analysis from
      the literature. RESULTS: At our center the prevalence of SMM was 0.9%. Our
      analysis comprised 38 patients with 67 muscle metastases. All identified SMM
      presented as intramuscular focal abnormal activity with SUV ranging from 2.4 to
      25.9, median SUV 7.8. The median size of the muscle metastases was 2.5 cm (range,
      0.6-6.5 cm). There were no significant differences between SUV and size of SMM
      arising from lung cancer, renal cell carcinoma, and esophageal cancer. Also,
      there was no correlation between SUV and size of SMM (r = 0.101, P = 0.558) and
      between SUV of SMM and primary tumors (r = 0.138, P = 0.686). In nine (23.7%) of
      the 38 patients, the identified SMM were isolated distant metastases or isolated
      tumor recurrence. CONCLUSION: SMM manifested on PET/CT as focal hypermetabolic
      intramuscular areas with different SUV. There were no significant differences
      between SUV or size of the identified SMM in esophageal cancer, renal cell
      carcinoma, and lung cancer.

PMID- 23884842
TI  - Fish bone foreign bodies in the pharynx and upper esophagus: evaluation with 64
      slice MDCT.
AB  - BACKGROUND: Fish bone (FB) is one of the common causes of foreign body impaction
      in the pharynx and esophagus. PURPOSE: To investigate the efficacy of 64-slice
      multidetector computed tomography (MDCT) for the evaluation of pharynx and upper
      esophageal FB foreign bodies. MATERIAL AND METHODS: Sixty-six patients with
      suspected FB foreign body ingestion were examined by plain radiography (n = 40)
      and unenhanced MDCT (n = 66). We analyzed the presence, location, size, shape,
      and lying position of the foreign bodies. RESULTS: On MDCT, 46 foreign bodies
      were detected. Among them, 45 were confirmed by endoscopy. The sensitivity of
      MDCT for the detection of foreign bodies was 100%, which was superior to that of
      the plain radiography (51.7%). The location of the foreign bodies was most common
      in the upper esophagus (n = 22, 47.8%), followed by pharyngoesophageal junction
      (n = 10, 21.7%), transjunctional (n = 7, 15.2%), hypopharynx (n = 5, 10.9%), and
      oropharynx (n = 2, 4.3%). Their longest length was 5.3-40.1 mm (mean, 21.3 mm).
      Thirty-three FBs (71.7%) were linear and 13 (28.3%) were flat in shape. They
      showed transverse (n = 23, 50.0%), parallel (n = 13, 28.3%), and oblique
      positions (n = 10, 21.7%) to the long axis of the pharynx and esophagus,
      respectively. CONCLUSION: MDCT is useful for the evaluation of the pharynx and
      upper esophageal FB foreign bodies.

PMID- 23884843
TI  - Biocalcification using B. pasteurii for strengthening brick masonry civil
      engineering structures.
AB  - Microbiologically induced calcite precipitation in bricks by bacterium Bacillus
      pasteurii (NCIM 2477) using a media especially optimized for urease production
      (OptU) was demonstrated in this study. Effect of biocalcification activity on
      compressive strength and water absorption capacity of bricks was investigated.
      Various other parameters such as pH, growth profile, urease activity, urea
      breakdown and calcite precipitated were monitored during the 28 days curing
      period. Efficiency of B. pasteurii to form microbial aided calcite precipitate in
      OptU media resulted into 83.9% increase in strength of the bricks as compared to
      only 24.9% with standard media, nutrient broth (NB). In addition to significant
      increase in the compressive strength, bricks treated with B. pasteurii grown in
      OptU media resulted in 48.9 % reduction in water absorption capacity as compared
      to control bricks immersed in tap water. Thus it was successfully demonstrated
      that microbial calcification in optimized media by Bacillus pasteurii has good
      potential for commercial application to improve the life span of structures
      constructed with bricks, particularly structures of heritage importance.

PMID- 23884845
TI  - Periocular aesthetic rejuvenation. Preface.

PMID- 23884844
TI  - Production of the Phanerochaete flavido-alba laccase in Aspergillus niger for
      synthetic dyes decolorization and biotransformation.
AB  - We investigated the expression of Phanerochaete flavido-alba laccase gene in
      Aspergillus niger and the physical and biochemical properties of the recombinant
      enzyme (rLac-LPFA) in order to test it for synthetic dye biotransformation. A.
      niger was able to produce high levels of active recombinant enzyme (30 mgL(-1)),
      whose identity was further confirmed by immunodetection using Western blot
      analysis and N-terminal sequencing. Interestingly, rLac-LPFA exhibited an
      improved stability at pH (2-9) and organic solvents tested. Furthermore, the
      percentage of decoloration and biotransformation of synthetic textile dyes,
      Remazol Brilliant Blue R (RBBR) and Acid Red 299 (NY1), was higher than for the
      native enzyme. Its high production, simple purification, high activity, stability
      and ability to transform textile dyes make rLac-LPFA a good candidate for
      industrial applications. 

PMID- 23884846
TI  - Clinical anatomy of the periocular region.
AB  - The aims of this article are twofold: (1) to provide the facial plastic surgeon
      with a comprehensive and up-to-date overview of periocular anatomy including the
      brow, midface, and temporal region and (2) to highlight important anatomical
      relationships that must be appreciated in order to achieve the best possible
      functional and aesthetic surgical outcomes. 

PMID- 23884847
TI  - The "bespoke" upper eyelid blepharoplasty and brow rejuvenation.
AB  - Blepharoplasty of the upper eyelids is one of the most commonly performed
      procedures in aesthetic plastic surgery. In this article, we describe our
      approach to the patient with aging of the periorbita. At all times, the approach
      is tailored to the individual's needs, trying to achieve a natural result that
      will not in any way affect the function of the eyelid. Our current approach and
      techniques for upper eyelid blepharoplasty and brow lifting are described. 

PMID- 23884848
TI  - Lower eyelid and midface rejuvenation.
AB  - Lower eyelid blepharoplasty is one of the most common procedures in aesthetic
      plastic surgery. Although patients desiring lower eyelid blepharoplasty typically
      describe their problem as "bags in the lower eyelids," there are many anatomical
      imperfections that should be assessed. With aging, the youthful single convexity
      of the lower lid separates into a double convexity with a valley at the
      intersection of the lower lid and midface. Midface descent further drags this
      intersection inferiorly, leading to a vertically lengthened lower eyelid. This
      article discusses how to clinically evaluate lower lid deformities, how to
      formulate a surgical plan, the preoperative assessment, and surgical markings.
      The rationale and anesthetic technique for outpatient versus in-office surgery is
      reviewed, and a detailed step-by-step approach with accompanying figures for
      lower lid blepharoplasty via a transconjunctival or transcutaneous incision is
      given. An approach to vertically supporting the lower eyelid is presented. 

PMID- 23884849
TI  - Complications of blepharoplasty.
AB  - This article provides a comprehensive discussion on the complications of
      blepharoplasty. We discuss the importance of preoperative counselling and
      surgical planning to provide the patient with a satisfactory outcome. Strategies
      are presented to manage common complications. 

PMID- 23884850
TI  - Midface-lifting: evolution, indications, and technique.
AB  - The youthful face is often defined by malar and lateral cheek fullness with
      associated submalar concavity, giving a smooth contour between the different
      subunits coupled with an aesthetically pleasing convex lower eyelid-cheek
      continuum. This article reviews the key anatomical concepts of midfacial aging,
      the evolution of midface-lifting techniques, and indications and
      contraindications for their use. 

PMID- 23884851
TI  - Minimally invasive periorbital rejuvenation.
AB  - Minimally invasive procedures have become increasingly popular over the last
      decade. In many cases, the use of neuromodulators and fillers has replaced
      surgical procedures. This article reviews the analysis and evaluation of the
      aesthetic patient presenting for periorbital rejuvenation. A layered approach is
      used, evaluating the skin, fat, muscle, and bone to determine which procedure is
      best suited for each patient. Volume enhancement with the use of fat and fillers
      and muscle manipulation with the use of neuromodulators are discussed. A brief
      summary of currently available skin-resurfacing techniques is also discussed. 

PMID- 23884852
TI  - Management of injuries of the eye and its adnexa.
AB  - The face plays the main role in interpersonal communication and in aesthetic
      perception. What is more, on account of the complex eyelid anatomy required to
      ensure the functioning of the eye, the treatment of periocular injuries requires
      a profound knowledge of anatomy and plastic reconstructive surgery, even if a
      loss of soft tissue is involved. Many methods for the reconstruction of eyelid
      defects have been described in the current literature. These methods must be
      guided by the site and extent of the defect on the one hand and by cosmetic
      requirements on the other to produce best results in terms of form and function.
      The treatment of injuries in the area of the eyelid involves some peculiarities
      that must be considered. The management of large defects in particular requires
      the cooperation of all head surgery disciplines. 

PMID- 23884853
TI  - Radiologic measurement of submandibular gland ptosis.
AB  - OBJECTIVE: Ptosis of the submandibular glands is a well-recognized yet poorly
      quantified element of the aging face and neck. The goal of this study is to
      describe and quantify the rate and extent of age-related submandibular gland
      ptosis. A novel grading system is proposed to quantify the degree of descent of
      the submandibular gland in relation to the inferior border of the mandible.
      Implications for facial rejuvenation surgery are discussed. STUDY DESIGN:
      Retrospective review. METHODS: Consecutive computed tomography (CT) imaging
      studies performed at a university-affiliated hospital were selected for review.
      Using cross-referenced images in the coronal and axial planes, distance
      measurements were obtained from the bottom of the submandibular gland to the
      plane of the inferior border of the mandible. These data points were plotted
      against subject age for statistical analysis. The position of the submandibular
      gland was then categorized as grade I when distance below the mandible was < 20
      mm, grade II for 20 to 25 mm, grade III for 25 to 30 mm, and grade IV for > 30
      mm. Volumetric analysis was performed in a subset of subjects to assess for the
      possibility of age-related submandibular gland volume changes as a potential
      confounding factor in distance measurements. RESULTS: One hundred consecutive CT
      imaging studies were selected for review (50 men, 50 women). A statistically
      significant linear relationship was identified between subject age and ptosis of
      the submandibular gland (r = 0.52, p < 0.001), as measured by the distance from
      the bottom of the submandibular gland from the plane of the inferior border of
      the mandible. The average rate of descent was 0.17 mm per year. Overall, the
      position of the submandibular gland was categorized as grade I in 18% of
      patients, grade II in 27% of patients, grade III in 32% of patients, and grade IV
      in 23% of patients. No statistically significant gender differences were
      identified in any of the data points. Volumetric analysis did not demonstrate any
      age-related changes in submandibular gland volume, and as such, this was excluded
      as a potential confounding factor in distance measurements. CONCLUSION: A linear
      relationship exists between patient age and submandibular gland ptosis, as
      measured by the distance of the gland from the inferior border of the mandible.
      To our knowledge, this is the first quantification of the rate and extent of
      submandibular gland ptosis. A novel grading system for submandibular gland ptosis
      has been proposed.

PMID- 23884854
TI  - Anthropometric measurements in 126 microtia reconstructions.
AB  - BACKGROUND: Due to its complex, three-dimensional morphology, auricular
      reconstruction remains one of the most challenging procedures in reconstructive
      surgery. A subject that remains controversial, however, is the question of the
      growth potential of the cartilaginous framework. This study explored the
      anthropometric changes of the reconstructed auricle and the contralateral normal
      ear in a series of Asian patients. METHODS: The records of 126 unilateral
      microtia patients in three age groups who underwent autogenous costal cartilage
      auricular reconstruction between 2007 and 2010 were reviewed. The average age was
      14 years, and the average follow-up was 2.5 years. The auricular height was
      measured as the distance from the supra-auricle to the subauricle, and the width
      was measured as the distance from preauricle to the postauricle. Measurements of
      the height and width of the reconstructed auricle and the contralateral normal
      side were taken at implantation and at the final follow-up. Comparisons between
      the three age groups were performed using a paired Student t test to examine the
      mean auricular heights and widths for significant interval changes in size.
      RESULTS: The measurements showed average width increases of 1.24 mm (3.68%) and
      1.35 mm (3.91%) in the reconstructed auricles of children and adolescents,
      respectively, but we did not find obvious changes in the adult group. No
      significant differences were found in the height measurement of the reconstructed
      auricle in the three groups. The mature size of the normal ear was reached by age
      12, with slowing as patients entered adolescence and adulthood. Comparison of the
      reconstructed auricle and the contralateral normal ear revealed a very similar
      growth rate in the adult group. There were average height decreases of 0.77 mm
      (1.3%) and 1.3 mm (2.09%) in the reconstructed auricles of children and
      adolescents compared with the normal side. The results showed an average width
      increase of 1.13 mm (3.15%) in the adolescent group but not in the child or adult
      groups. CONCLUSIONS: The results of this study have generated some useful
      parameters for the study of growth of the reconstructed auricle and contralateral
      normal ear. This information serves to clarify the issue of auricular framework
      fabrication in terms of proper size, especially for Asian patients. Further
      investigation and analysis are necessary to provide further proof of the graft
      change.

PMID- 23884855
TI  - Depletion of the nasal reserve after a mole excision.
AB  - The authors present an original case report to warn of a possible severe
      functional complication that might follow a simple facial skin procedure. A 55
      year-old woman underwent excision of a mole along the alar-facial groove, which
      seemingly healed without immediate complications. Ultimately the patient reported
      an ipsilateral nasal obstruction 2 months postoperatively. Intranasal inspection
      and a computed tomography scan revealed a severe septum deviation that had been
      previously clinically unapparent. The authors argue that the skin-scarring
      process progressively counterbalanced the action of the levator labii superioris
      alaeque nasi muscle fascicle to the nostril. Such an action had been compensating
      for a subtotally compromised nasal air flow from a preexisting severe septal
      deviation. In this context, skin scarring was enough to impair a minimal residual
      nasal respiratory reserve. The authors therefore advise performing an internal
      nasal inspection at all times prior to any sort of skin surgery around the alar
      facial groove. This will allow detection of any subclinical functionally
      compensated preexisting septal deviation or any other intranasal obstruction that
      could manifest at a later stage. 

PMID- 23884856
TI  - Quality by design: scale-up of freeze-drying cycles in pharmaceutical industry.
AB  - This paper shows the application of mathematical modeling to scale-up a cycle
      developed with lab-scale equipment on two different production units. The above
      method is based on a simplified model of the process parameterized with
      experimentally determined heat and mass transfer coefficients. In this study, the
      overall heat transfer coefficient between product and shelf was determined by
      using the gravimetric procedure, while the dried product resistance to vapor flow
      was determined through the pressure rise test technique. Once model parameters
      were determined, the freeze-drying cycle of a parenteral product was developed
      via dynamic design space for a lab-scale unit. Then, mathematical modeling was
      used to scale-up the above cycle in the production equipment. In this way,
      appropriate values were determined for processing conditions, which allow the
      replication, in the industrial unit, of the product dynamics observed in the
      small scale freeze-dryer. This study also showed how inter-vial variability, as
      well as model parameter uncertainty, can be taken into account during scale-up
      calculations. 

PMID- 23884857
TI  - The protective role of resveratrol in the sodium arsenite-induced oxidative
      damage via modulation of intracellular GSH homeostasis.
AB  - Sodium arsenite (NaAsO2) is a well-established environmental carcinogen that has
      been found to cause various human malignant tumors. Thus, how to prevent the
      deleterious effects caused by NaAsO2 has received widely concerns. Resveratrol
      (3,4',5-trihydroxystilbene), a polyphenol found in numerous plant species, has
      recently been known as a natural and powerful antioxidant. However, whether
      resveratrol could attenuate the toxicity of NaAsO2 and its detailed mechanisms
      have not been reported. In this study, the protective effects of resveratrol
      against NaAsO2-induced oxidative and genetic damage as well as apoptosis were
      evaluated for the first time. We demonstrated that cotreatment of human bronchial
      epithelial cell with 5 MUM resveratrol for 24 h effectively reduced the levels of
      30 MUM NaAsO2-induced reactive oxygen species, chromosomal and DNA damage, and
      cell apoptosis. Revseratrol was also showed to significantly elevate the
      concentration of glutathione (GSH) and the activities of its relevant enzymes as
      compared with NaAsO2 alone, indicating that resveratrol ameliorates the toxicity
      of NaAsO2 by modulating the process of GSH biosynthesis, recycling and
      utilization. Our findings further suggest that GSH homeostasis represents one of
      the detoxification mechanisms responding to NaAsO2 exposure, and resveratrol
      plays a protective role in the regulation of oxidative and genetic damage as well
      as apoptosis through the modulation of GSH homeostasis.

PMID- 23884858
TI  - COP1 targets C/EBPalpha for degradation and induces acute myeloid leukemia via
      Trib1.
AB  - The ubiquitin ligase constitutively photomorphogenic 1 (COP1) is involved in many
      biological responses in mammalian cells, but its role in tumorigenesis remains
      unclear. Here we show that COP1 is a ubiquitin ligase for the tumor suppressor
      CCAAT/enhancer-binding protein (C/EBPalpha) and promotes its degradation in vivo,
      thereby blocking myeloid differentiation of hematopoietic cells for
      tumorigenesis. In this process, mammalian homolog of Tribbles, Trib1, which
      contains a COP1-binding motif, is essential for down-regulation of C/EBPalpha
      expression. Murine bone marrow transplantation experiments showed that
      coexpression of COP1 accelerates development of acute myeloid leukemia induced by
      Trib1, which pathologically resembles that of p42C/EBPalpha-deficient mice.
      Interestingly, coexpression of ligase activity-deficient COP1 mutant abrogated
      Trib1-induced leukemogenesis. These results indicate that COP1 and Trib1 act as
      an oncoprotein complex functioning upstream of C/EBPalpha, and its ligase
      activity is crucial for leukemogenesis.

PMID- 23884859
TI  - Specific gene delivery to liver sinusoidal and artery endothelial cells.
AB  - Different types of endothelial cells (EC) fulfill distinct tasks depending on
      their microenvironment. ECs are therefore difficult to genetically manipulate ex
      vivo for functional studies or gene therapy. We assessed lentiviral vectors (LVs)
      targeted to the EC surface marker CD105 for in vivo gene delivery. The mouse
      CD105-specific vector, mCD105-LV, transduced only CD105-positive cells in primary
      liver cell cultures. Upon systemic injection, strong reporter gene expression was
      detected in liver where mCD105-LV specifically transduced liver sinusoidal ECs
      (LSECs) but not Kupffer cells, which were mainly transduced by nontargeted LVs.
      Tumor ECs were specifically targeted upon intratumoral vector injection. Delivery
      of the erythropoietin gene with mCD105-LV resulted in substantially increased
      erythropoietin and hematocrit levels. The human CD105-specific vector (huCD105
      LV) transduced exclusively human LSECs in mice transplanted with human liver ECs.
      Interestingly, when applied at higher dose and in absence of target cells in the
      liver, huCD105-LV transduced ECs of a human artery transplanted into the
      descending mouse aorta. The data demonstrate for the first time targeted gene
      delivery to specialized ECs upon systemic vector administration. This strategy
      offers novel options to better understand the physiological functions of ECs and
      to treat genetic diseases such as those affecting blood factors. 

PMID- 23884860
TI  - Spermatogonial behavior in rats during radiation-induced arrest and recovery
      after hormone suppression.
AB  - Ionizing radiation has been shown to arrest spermatogenesis despite the presence
      of surviving stem spermatogonia, by blocking their differentiation. This block is
      a result of damage to the somatic environment and is reversed when gonadotropins
      and testosterone are suppressed, but the mechanisms are still unknown. We
      examined spermatogonial differentiation and Sertoli cell factors that regulate
      spermatogonia after irradiation, during hormone suppression, and after hormone
      suppression combined with Leydig cell elimination with ethane dimethane
      sulfonate. These results showed that the numbers and cytoplasmic structure of
      Sertoli cells are unaffected by irradiation, only a few type A undifferentiated
      (Aund) spermatogonia and even fewer type A1 spermatogonia remained, and
      immunohistochemical analysis showed that Sertoli cells still produced KIT ligand
      (KITLG) and glial cell line-derived neurotrophic factor (GDNF). Some of these
      cells expressed KIT receptor, demonstrating that the failure of differentiation
      was not a result of the absence of the KIT system. Hormone suppression resulted
      in an increase in Aund spermatogonia within 3 days, a gradual increase in KIT
      positive spermatogonia, and differentiation mainly to A3 spermatogonia after 2
      weeks. KITL (KITLG) protein expression did not change after hormone suppression,
      indicating that it is not a factor in the stimulation. However, GDNF increased
      steadily after hormone suppression, which was unexpected since GDNF is supposed
      to promote stem spermatogonial self-renewal and not differentiation. We conclude
      that the primary cause of the block in spermatogonial development is not due to
      Sertoli cell factors such (KITL?GDNF) or the KIT receptor. As elimination of
      Leydig cells in addition to hormone suppression resulted in differentiation to
      the A3 stage within 1 week, Leydig cell factors were not necessary for
      spermatogonial differentiation. 

PMID- 23884861
TI  - The roles of melanin-concentrating hormone in energy balance and reproductive
      function: Are they connected?
AB  - Melanin-concentrating hormone (MCH) is an anabolic neuropeptide with multiple and
      diverse physiological functions including a key role in energy homoeostasis.
      Rodent studies have shown that the ablation of functional MCH results in a lean
      phenotype, increased energy expenditure and resistance to diet-induced obesity.
      These findings have generated interest among pharmaceutical companies vigilant
      for potential anti-obesity agents. Nutritional status affects reproductive
      physiology and behaviours, thereby optimising reproductive success and the
      ability to meet energetic demands. This complex control system entails the
      integration of direct or indirect peripheral stimuli with central effector
      systems and involves numerous mediators. A role for MCH in the reproductive axis
      has emerged, giving rise to the premise that MCH may serve as an integratory
      mediator between those discrete systems that regulate energy balance and
      reproductive function. Hence, this review focuses on published evidence
      concerning i) the role of MCH in energy homoeostasis and ii) the regulatory role
      of MCH in the reproductive axis. The question as to whether the MCH system
      mediates the integration of energy homoeostasis with the neuroendocrine
      reproductive axis and, if so, by what means has received limited coverage in the
      literature; evidence to date and current theories are summarised herein. 

PMID- 23884862
TI  - Influence of infection during pregnancy on fetal development.
AB  - Infection by bacteria, viruses, and parasites may lead to fetal death, organ
      injury, or limited sequelae depending on the pathogen. Here, we consider the role
      of infection during pregnancy in fetal development including placental
      development and function, which can lead to fetal growth restriction. The
      classical group of teratogenic pathogens is referred to as 'TORCH' (Toxoplasma
      gondii, others like Treponema pallidum, rubella virus, cytomegalovirus, and
      herpes simplex virus) but should include a much broader group of pathogens
      including Parvovirus B19, Varicella zoster virus, and Plasmodium falciparum to
      name a few. In this review, we describe the influence of different infections in
      utero on fetal development and the short- and long-term outcomes for the neonate.
      In some cases, the mechanisms used by these pathogens to disrupt fetal
      development are well known. Bacterial infection of the developing fetal lungs and
      brain begins with an inflammatory cascade resulting in cytokine injury and
      oxidative stress. For some pathogens like P. falciparum, the mechanisms involve
      oxidative stress and apoptosis to disrupt placental and fetal growth. An in utero
      infection may also affect the long-term health of the infant; in many cases, a
      viral infection in utero increases the risk of developing type 1 diabetes in
      childhood. Understanding the varied mechanisms employed by these pathogens may
      enable therapies to attenuate changes in fetal development, decrease preterm
      birth, and improve survival. 

PMID- 23884863
TI  - The size, burden and cost of disorders of the brain in the UK.
AB  - AIM: The aim of this paper is to increase awareness of the prevalence and cost of
      psychiatric and neurological disorders (brain disorders) in the UK. METHOD: UK
      data for 18 brain disorders were extracted from a systematic review of European
      epidemiological data and prevalence rates and the costs of each disorder were
      summarized (2010 values). RESULTS: There were approximately 45 million cases of
      brain disorders in the UK, with a cost of ?134 billion per annum. The most
      prevalent were headache, anxiety disorders, sleep disorders, mood disorders and
      somatoform disorders. However, the five most costly disorders (? million) were:
      dementia: ?22,164; psychotic disorders: ?16,717; mood disorders: ?19,238;
      addiction: ?11,719; anxiety disorders: ?11,687. Apart from psychosis, these five
      disorders ranked amongst those with the lowest direct medical expenditure per
      subject (<?3000). The approximate breakdown of costs was: 50% indirect costs, 25%
      direct non-medical and 25% direct healthcare costs. DISCUSSION: The prevalence
      and cost of UK brain disorders is likely to increase given the ageing population.
      Translational neurosciences research has the potential to develop more effective
      treatments but is underfunded. Addressing the clinical and economic challenges
      posed by brain disorders requires a coordinated effort at an EU and national
      level to transform the current scientific, healthcare and educational agenda.

PMID- 23884864
TI  - DNA barcoding survey of Trichoderma diversity in soil and litter of the Colombian
      lowland Amazonian rainforest reveals Trichoderma strigosellum sp. nov. and other
      species.
AB  - The diversity of Trichoderma (Hypocreales, Ascomycota) colonizing leaf litter as
      well as the rhizosphere of Garcinia macrophylla (Clusiaceae) was investigated in
      primary and secondary rain forests in Colombian Amazonia. DNA barcoding of 107
      strains based on the internal transcribed spacers 1 and 2 (ITS1 and 2) of the
      ribosomal RNA gene cluster and the partial sequence of the translation elongation
      factor 1 alpha (tef1) gene revealed that the diversity of Trichoderma was
      dominated (71 %) by three common cosmopolitan species, namely Trichoderma
      harzianum sensu lato (41 %), Trichoderma spirale (17 %) and Trichoderma
      koningiopsis (13 %). Four ITS 1 and 2 phylotypes (13 strains) could not be
      identified with certainty. Multigene phylogenetic analysis and phenotype
      profiling of four strains with an ITS1 and 2 phylotype similar to Trichoderma
      strigosum revealed a new sister species of the latter that is described here as
      Trichoderma strigosellum sp. nov. Sequence similarity searches revealed that this
      species also occurs in soils of Malaysia and Cameroon, suggesting a pantropical
      distribution. 

PMID- 23884865
TI  - Optimizing the use of anticoagulants (heparins and oral anticoagulants) in the
      elderly.
AB  - As longevity constantly increases, the number of elderly patients (75 years and
      older) who require anticoagulation likewise rises steadily. Managing elderly
      patients receiving anticoagulants is challenging because those patients are at
      high risk of both thrombosis and bleeding. Moreover, older patients are commonly
      frail: they have substantial chronic co-morbid conditions including renal
      impairment and frequent acute illnesses and are often polymedicated. There
      remains a clear need to optimize the use of anticoagulant drugs in these
      patients, especially at full anticoagulant dose. In the last decade, efforts have
      been made to better understand the inter-individual variability in the response
      of elderly patients to traditional anticoagulants including heparin derivatives
      (unfractionated heparin, low molecular weight heparins and fondaparinux) and
      vitamin K antagonists. Moreover, their safety profile has been evaluated in
      different settings in the elderly, assisting in minimizing risks related to their
      use. Emergence of new oral anticoagulants (dabigatran, rivaroxaban, apixaban),
      which appear to be much more convenient, is promising. Even though some elderly
      patients were included in pivotal clinical trials evaluating these new
      anticoagulants, the safety of these drugs remains uncertain in real life.

PMID- 23884866
TI  - Antibiotic prophylaxis in children with cancer or who have undergone
      hematopoietic cell transplantation.
AB  - Bacterial infections are common in children with cancer and can lead to life
      threatening complications. Infections in these patients mainly occur during
      neutropenic periods, and may be caused by Gram-positive or Gram-negative
      bacteria. The patients at highest risk of serious infections include those with
      acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), and those
      undergoing myeloablative hematopoietic cell transplantation (HCT). This is a
      review with the main aim of making a critical appraisal of the literature, and
      summarising what is currently known and can be recommended. The most significant
      studies support the use of floroquinolones (mainly ciprofloxacin) as the most
      rational approach to treat pediatric patients with probably long-lasting
      neutropenia, although trimetoprim-sulphametoxazole and amoxicillin/clavulanate
      may theoretically be valid alternatives. No prophylaxis seems to be needed for
      children with cancer without severe neutropenia. However, a global evaluation of
      the studies of antibiotic prophylaxis in children with cancer indicates that
      there are not enough data to prepare definite guidelines for its use or avoidance
      in pediatric oncology, and so further studies are needed. It is not only
      important to define the best antibiotic regimens for the children in whom such
      prophylaxis is useful, but also to identify precisely those who do not need it.
      This would avoid the antibiotic misuse that probably occurs at the moment because
      many low-risk children with cancer are treated. As prophylaxis against infections
      requires long-term adherence to an antibiotic regimen, the attitudes and beliefs
      of stakeholders need to be fully considered. 

PMID- 23884867
TI  - Proteomic analysis of apoptotic and oncotic pancreatic acinar AR42J cells treated
      with caerulein.
AB  - This study aims to determine the differentially expressed proteins in the
      pancreatic acinar cells undergoing apoptosis and oncosis stimulated with
      caerulein to explore different cell death process of the acinar cell. AR42J cells
      were treated with caerulein to induce cell model of acute pancreatitis. Cells
      that were undergoing apoptosis and oncosis were separated by flow cytometry. Then
      differentially expressed proteins in the two groups of separated cells were
      detected by shotgun liquid chromatography-tandem mass spectrometry. The results
      showed that 11 proteins were detected in both apoptosis group and oncosis group,
      17 proteins were detected only in apoptosis group and 29 proteins were detected
      only in oncosis group. KEGG analysis showed that proteins detected only in
      apoptosis group were significantly enriched in 10 pathways, including ECM
      receptor interaction, cell adhesion molecules, and proteins detected only in
      oncosis group were significantly enriched in three pathways, including
      endocytosis, base excision repair, and RNA degradation. These proteins we
      detected are helpful for us to understand the process of cell death in acute
      pancreatitis and may be useful for changing the death mode of pancreatic acinar
      cells, thus attenuating the severity of pancreatitis. 

PMID- 23884868
TI  - [Mnemonic complaints and chronic migraine].
AB  - INTRODUCTION. Patients with chronic migraine often report lower cognitive
      performance, which affects their quality of life. AIMS. To analyse whether the
      mnemonic capacity of patients with chronic migraine is altered or not. SUBJECTS
      AND METHODS. A cross-sectional study was conducted in patients with chronic
      migraine evaluated consecutively in our unit, and paired by age (18-60 years) and
      gender with a control group consisting of cognitively healthy volunteers. The
      following cognitive instruments were administered: Folstein Minimental State
      Examination (MMSE), Memory Alteration Test (M@T), Montreal Cognitive Assessment
      (MoCA) and working memory. RESULTS. A total of 30 patients with chronic migraine
      were included (mean age: 49.33 +/- 10.05 years) paired with a control group of 30
      healthy volunteers (mean age: 44.83 +/- 10.91 years). The mean elapsed time since
      onset of the patients with chronic migraine was 4.47 +/- 2.74 years. On
      performing a comparative analysis between the two groups, significant differences
      were found with overall lower scores in the group of patients with chronic
      migraine in the MoCA (24.16 versus 29), M@T (43.76 versus 48.8) and working
      memory tests (17.5 versus 24.26). Performance in the MMSE was similar in both
      groups. CONCLUSIONS. Patients with chronic migraine can have lower cognitive
      performance regardless of distracting elements, such as pharmacological factors
      or psychiatric comorbidity, since chronic migraine can be understood as yet
      another element within the spectrum of chronic pain. 

PMID- 23884869
TI  - [Evaluation of the community integration of persons with lateralised post-acute
      acquired brain injury].
AB  - INTRODUCTION. Hemispheric specialization is a topic of interest that has
      motivated an enormous amount of research in recent decades. After a unilateral
      brain injury, the consequences can affect various areas of specialization,
      leading, depending on the location of the injury, impairment in quality of life
      and community integration. PATIENTS AND METHODS. Cross-sectional study with a
      sample of 58 patients, 28 traumatic brain injury (TBI) and 30 cerebrovascular
      accidents, both lateralized. The level of integration in the community is
      measured by the Community Integration Questionnaire. RESULTS. There were three
      groups analyzed by considering unilateral injury (full sample, stroke sample, and
      TBI sample). Results showed a significantly high community integration of people
      with right hemisphere injury. However, to measure the level of community
      integration between TBI and stroke, the results showed no significant
      differences. CONCLUSION. According to the results of the study people with brain
      injury in the right hemisphere have a better community integration than people
      with lesions in the left hemisphere regardless of the origin of the lesions
      (vascular or traumatic). We discussed the reasons that may motivate the
      differences and clinical implications. 

PMID- 23884870
TI  - [Co-authorship and collaboration networks in Spanish research into multiple
      sclerosis (1996-2010)].
AB  - INTRODUCTION. Scientific collaboration is vital for to the advance of knowledge
      and is especially important in health sciences. The aim of this study is to
      identify scientific collaboration indicators and co-authorship networks of
      researchers and Spanish institutions that publish on multiple sclerosis (MS)
      during the period 1996-2010. MATERIALS AND METHODS. The analyzed papers were
      obtained from Web of Science and Scopus international databases, and IBECS and
      IME national databases, applying specific search profiles in each one of them. In
      order to identify collaboration networks all signed papers were quantified and co
      authored measures were obtained, as the different indexes, degree, intermediation
      and closeness. RESULTS. 1,613 articles were published in the period 1996-2010,
      92% of them in collaboration. With 10 or more works signed in collaboration, 20
      Spanish research groups in MS were identified. 64.23% of the papers were
      published in collaboration between Spanish institutions, and 33.85% were in
      collaboration with foreign institutions. The institutional participation analysis
      has identified a large network of institutional partnerships that integrates 27
      institutions, with the Hospital Vall d'Hebron in a central position.
      International collaboration is headed by the U.S. and European countries, most
      notably the UK and Italy. CONCLUSION. The most collaborative authors,
      institutions, and work groups in Spanish research in MS have been identified.
      Despite these indicators that characterize the collaboration in this area, it is
      necessary to enhance cooperation between them, since this collaboration is
      positively related to the quality and impact of research and publications. 

PMID- 23884871
TI  - [Diagnosis of stroke due to cocaine and its complications].
AB  - INTRODUCTION. Cocaine is an independent cerebrovascular risk factor both for
      ischaemic and haemorrhagic events, above all among persons under 55 years of age.
      CASE REPORT. A case report of stroke due to the consumption of cocaine is used to
      review its pathophysiology and the complexity involved in the management and
      diagnosis of the associated complications. One of these complications reported in
      relation to the consumption of cocaine is vasospasm. This condition shares
      findings observed in ultrasound imaging studies with other conditions, such as
      early-onset post ischaemic hyperperfusion. Yet, there are important differences
      between the two as regards their treatment and prognosis. CONCLUSIONS. The
      consumption of cocaine is associated with cerebrovascular disease through a
      number of different mechanisms, which each give rise to different complications.
      By identifying these complications, correct management can be implemented. 

PMID- 23884872
TI  - [Cytokines and the nervous system: the relationship between seizures and
      epilepsy].
AB  - INTRODUCTION. The immune system and the peripheral and central nervous system are
      in constant communication by means of messengers and signalling molecules
      released, such as cytokines, neuropeptides, neurohormones and neurotransmitters,
      among others. Seizures are defined as the transitory appearance of signs and
      symptoms that trigger an abnormally excessive neuronal activity in the brain.
      Following seizures the generation of a neuroinflammatory process has been
      observed to occur, with the consequent release of proinflammatory cytokines and
      inflammation-mediating molecules, which make the patient more prone to epilepsy.
      AIM. To offer evidence suggesting and supporting the role of cytokines in the
      appearance of seizures and in epilepsy, since these molecules have proven to have
      dual properties. DEVELOPMENT. The central nervous system, by means of the blood
      brain barrier, restricts the flow of activated cells and inflammation mediators
      released from the peripheral system towards the brain parenchyma. Moreover, there
      is also another series of mechanisms that contributes to the 'selective and
      modified' immunity of the central nervous system. The purpose of all this series
      of events is to limit the responses of the immune system at central level,
      although it has been shown that in the central nervous system they are
      permanently under the control and regulation of the immune system. CONCLUSIONS.
      Cytokines in epilepsy play a dual role with pro- and anti-convulsive properties.
      Seizures do not induce the expression of cytokines only inside the brain, but
      also peripherally. 

PMID- 23884874
TI  - [Cervicodorsal myelitis secondary to infection by varicella zoster virus in an
      immunocompetent patient].

PMID- 23884875
TI  - Sevoflurane therapy for life-threatening asthma in children.
AB  - BACKGROUND: Asthma is a common disease in children and often develops early in
      life. This multicentre retrospective case series describe the use and
      effectiveness of sevoflurane inhalation therapy in a series of children with
      severe asthma in the paediatric intensive care unit (PICU). METHODS: Seven
      children ranging from 4 to 13 yr of age admitted to the PICU of two tertiary care
      hospitals in the Netherlands were included. They all were admitted with the
      diagnosis of severe asthma requiring invasive mechanical ventilation and were
      treated with sevoflurane inhalation therapy. RESULTS: The median (range) Pco2
      level at the start, after 2 h, and at the end of sevoflurane treatment were 14
      (5.1-24.8), 9.8 (5.4-17.0), and 6.2 (4.5-11.4) kPa (P=0.05) while the median
      (range) pH was 7.02 (6.97-7.36), 7.18 (7.04-7.35), and 7.43 (7.15-7.47) kPa
      (P=0.01), respectively. The median (range) peak pressure values declined from 30
      (23-56) to 20.4 (14-33) cm H2O (P=0.03). No severe adverse effects besides
      hypotension, with sufficient response to norepinephrine treatment, were seen.
      CONCLUSIONS: Sevoflurane inhalation corrects high levels of Pco2 and provides
      clinical improvement in mechanically ventilated children with life-threatening
      asthma who fail to respond to conventional treatment.

PMID- 23884876
TI  - Acute hyperglycemia together with hematoma of high-glucose blood exacerbates
      neurological injury in a rat model of intracerebral hemorrhage.
AB  - Recent evidence suggests that admission hyperglycemia has deleterious effects on
      the survival and functional outcome of patients with intracerebral hemorrhage
      (ICH). In this study, we first induced acute hyperglycemia in male adult Sprague
      Dawley rats by intraperitoneal injection of 50% glucose (6 mL/kg), and created
      the ICH model thereafter by delivering autologous whole blood or homologous
      normal-glucose blood into the right basal ganglia. Twenty-four hours later, we
      assessed the neurological injury, evaluated the hematoma and brain water content,
      and investigated autophagy. We found elevations of neurological deficit scores,
      brain water content, and microtubule-associated protein light chain-3 (LC3) and
      beclin-1 protein levels, and decreased SQSTM1/ p62 levels after ICH with normal
      glucose blood (without hyperglycemia). Acute hyperglycemia with ICH of high
      glucose blood hematoma was associated with significantly increased forelimb-use
      asymmetry test scores, brain water content and SQSTM1/p62 protein levels, and
      evident decreases in the ratio of LC3-II/LC3-I and beclin-1 protein levels. On
      the other hand, acute hyperglycemia and ICH with normal-glucose blood hematoma
      only slightly increased the neurological deficit scores and brain water content
      (P >0.05). In conclusion, the autophagy pathway was activated after ICH, and
      acute hyperglycemia with hematoma of high-glucose blood exacerbates the
      neurological injury, and reduces autophagy around the hematoma.

PMID- 23884877
TI  - Heavy metal accumulation in edible fish species from Rawal Lake Reservoir,
      Pakistan.
AB  - The aim of the present study was to describe the accumulation of trace metals in
      the liver, kidney, gills, muscles, and skin of four edible fish species (Tor
      putitora, Cirrhinus mrigala, Labeo calbasu, and Channa punctatus) of Rawal Lake
      Reservoir, Pakistan. The fish samples were collected in the pre-monsoon (May
      2008) and post-monsoon (October 2007) seasons and were analyzed for heavy metals
      by using an atomic absorption spectrometer. Kidney and liver showed relatively
      high concentrations of heavy metals. The accumulation of metals in the different
      organs of the fish (skin, muscles, and gills) in post-monsoon was higher than in
      pre-monsoon. In pre-monsoon, the metals followed the trend Zn > Pb > Fe > Cr > Ni
      > Mn > Co > Cu > Cd > Li, while in the post-monsoon season, the trend was Fe > Pb
      > Cr > Ni > Zn > Cu > Co > Mn > Cd > Li. The concentrations of Ni, Cr, and Pb in
      the muscle of all fish species were higher than the WHO guideline values of heavy
      metals in fishes for human consumption except in T. putitora. Cu level was nearly
      equal to the WHO maximum levels in C. mrigala and L. calbasu, while it was lower
      in T. putitora and C. punctatus. It is strongly advocated that risk assessment
      studies should be conducted and there is an urgent need for water quality
      restoration and management of Rawal Lake Reservoir. 

PMID- 23884879
TI  - Use of bubble wrap for microsurgical training.

PMID- 23884878
TI  - Cytogenetic biomonitoring of primary school children exposed to air pollutants:
      micronuclei analysis of buccal epithelial cells.
AB  - There is an increasing attempt in the world to determine the exposures of
      children to environmental chemicals. To analyze the genotoxic effect of air
      pollution, micronucleus (MN) assay was carried out in buccal epithelial cells
      (BECs) of children living in an urban city of Turkey. Children from two schools
      at urban-traffic and suburban sites were investigated in summer and winter
      seasons for the determination of BEC-MN frequency (per mille) and frequency of
      BEC with MN (per mille). The same children were also recruited for lung function
      measurements within a MATRA project ("Together Towards Clean Air in Eskisehir and
      Iskenderun") Measured NO2 and SO2 concentrations did not exceed the European
      Union (EU) limit levels either in urban-traffic or suburban regions. Higher O3
      concentrations were measured in the suburban site especially in the summer
      period. Particulate matter (PM2.5 and PM10) levels which did not differ
      statistically between two regions were above the EU limits in general. Although
      BEC-MN frequencies of children living in the suburban sites were higher in
      general, the difference between two regions was not significant either in the
      summer or winter periods. BEC-MN frequencies of the urban-traffic children were
      found to be significantly higher in summer period (mean +/- SD, 2.68 +/- 1.99)
      when compared to winter period (1.64 +/- 1.59; p = 0.004). On the other hand, no
      seasonality was observed for the suburban children. Similar results have been
      obtained in the BEC frequency with MN in our study. In summer, BEC-MN frequencies
      were significantly increased with the decrease in pulmonary function levels based
      on forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) levels
      (p < 0.05). As a conclusion, children living in urban-traffic and suburban areas
      in the city of Eskisehir exhibited similar genotoxicity. Seasonal variation in
      genotoxicity may be interpreted as relatively high ozone levels and increasing
      time spent at outdoors in the summer.

PMID- 23884880
TI  - Anatomic variations in branching patterns of the axillary artery: a multidetector
      row computed tomography angiography study.
AB  - Anatomic variations in branching pattern of axillary artery (AxA) are common and
      typically involve subscapular artery (SsA) and posterior circumflex humeral
      artery (PCHA). Several skin and muscle flaps are based on the branches of AxA.
      Furthermore, these branches are frequently used as recipient vessels in
      functioning free muscle transfers for upper extremity reconstruction and in
      breast reconstruction. Accurate knowledge of the normal anatomy and variations in
      branching pattern of AxA is of significant clinical importance for the
      reconstructive microsurgeon. The purpose of this article is to report the
      variable branching pattern of AxA based on multidetector-row computed tomography
      angiography study of 62 upper extremities. The thoracoacromial artery
      consistently originated from the first or second part of AxA. The classic origin
      and branching patterns of SsA and PCHA were observed in 21 cases (33.9%).
      Anatomic variations of SsA and PCHA were observed in 41 upper extremities
      (66.1%). In addition to the classic pattern, five distinct variations were noted.

PMID- 23884881
TI  - Comparison of oversized artery and vein grafts for interpositional pedicle
      lengthening in rat femoral artery.
AB  - Vessel grafting is commonly used for revascularization or pedicle lengthening.
      Although veins are more commonly used, they can form aneurysms when bridging an
      arterial gap. This can lead to thrombosis, and the risk is increased when there
      is a size discrepancy. This study reports the long-term results of arterial
      lengthening via size discrepant carotid artery and femoral vein grafts in a rat
      femoral artery model (1:1.5 ratio). A total of 28 rats were used in this study,
      divided into two groups of 14. By the 21st day, one anastomosis in each group has
      been found to be thrombosed. Long-term patency rates were the same for both
      groups (93.3%). Radiologic imaging showed that size match in the carotid artery
      grafts was excellent despite of slightly fusiform dilatation, but in the vein
      groups, pronounced aneurismal deformation and distortion in the anastomosis was
      seen. Histologic analysis revealed that in the arterial grafts, endothelial
      continuity was smooth and mural inflammation was less than that of the vein
      grafts. Organized or recanalized mural thrombi were seen in 38.5% in the vein
      grafts, whereas in arterial grafts there were none. 

PMID- 23884882
TI  - Resveratrol prevents beta-cell dedifferentiation in nonhuman primates given a
      high-fat/high-sugar diet.
AB  - Eating a "Westernized" diet high in fat and sugar leads to weight gain and
      numerous health problems, including the development of type 2 diabetes mellitus
      (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood
      glucose levels, preserves beta-cells in islets of Langerhans, and improves
      insulin action. Although rodent models are helpful for understanding beta-cell
      biology and certain aspects of T2DM pathology, they fail to reproduce the
      complexity of the human disease as well as that of nonhuman primates. Rhesus
      monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in
      combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months,
      and pancreata were examined before overt dysglycemia occurred. Increased glucose
      stimulated insulin secretion and insulin resistance occurred in both HFS and
      HFS+Resv diets compared with SD. Although islet size was unaffected, there was a
      significant decrease in beta-cells and an increase in alpha-cells containing
      glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys
      were morphologically similar to SD. HFS diets also resulted in decreased
      expression of essential beta-cell transcription factors forkhead box O1 (FOXO1),
      NKX6-1, NKX2-2, and PDX1, which did not occur with resveratrol supplementation.
      Similar changes were observed in human islets where the effects of resveratrol
      were mediated through Sirtuin 1. These findings have implications for the
      management of humans with insulin resistance, prediabetes, and diabetes. 

PMID- 23884883
TI  - Profilin-1 haploinsufficiency protects against obesity-associated glucose
      intolerance and preserves adipose tissue immune homeostasis.
AB  - Metabolic inflammation may contribute to the pathogenesis of obesity and its
      comorbidities, including type 2 diabetes and cardiovascular disease. Previously,
      we showed that the actin-binding protein profilin-1 (pfn) plays a role in
      atherogenesis because pfn heterozygote mice (PfnHet) exhibited a significant
      reduction in atherosclerotic lesion burden and vascular inflammation. In the
      current study, we tested whether pfn haploinsufficiency would also limit diet
      induced adipose tissue inflammation and insulin resistance (IR). First, we found
      that a high-fat diet (HFD) upregulated pfn expression in epididymal and
      subcutaneous white adipose tissue (WAT) but not in the liver or muscle of C57BL/6
      mice compared with normal chow. Pfn expression in WAT correlated with F4/80, an
      established marker for mature macrophages. Of note, HFD elevated pfn protein
      levels in both stromal vascular cells and adipocytes of WAT. We also found that
      PfnHet were significantly protected from HFD-induced glucose intolerance observed
      in pfn wild-type mice. With HFD, PfnHet displayed blunted expression of systemic
      and WAT proinflammatory cytokines and decreased accumulation of adipose tissue
      macrophages, which were also preferentially biased toward an M2-like phenotype;
      this correlated with preserved frequency of regulatory T cells. Taken together,
      the findings indicate that pfn haploinsufficiency protects against diet-induced
      IR and inflammation by modulating WAT immune homeostasis. 

PMID- 23884884
TI  - Copper transporter ATP7A protects against endothelial dysfunction in type 1
      diabetic mice by regulating extracellular superoxide dismutase.
AB  - Oxidative stress and endothelial dysfunction contribute to vascular complication
      in diabetes. Extracellular superoxide dismutase (SOD3) is one of the key
      antioxidant enzymes that obtains copper via copper transporter ATP7A. SOD3 is
      secreted from vascular smooth muscles cells (VSMCs) and anchors at the
      endothelial surface. The role of SOD3 and ATP7A in endothelial dysfunction in
      type 1 diabetes mellitus (T1DM) is entirely unknown. Here we show that the
      specific activity of SOD3, but not SOD1, is decreased, which is associated with
      increased O2(*-) production in aortas of streptozotocin-induced and genetically
      induced Ins2(Akita) T1DM mice. Exogenous copper partially rescued SOD3 activity
      in isolated T1DM vessels. Functionally, acetylcholine-induced, endothelium
      dependent relaxation is impaired in T1DM mesenteric arteries, which is rescued by
      SOD mimetic tempol or gene transfer of SOD3. Mechanistically, ATP7A expression in
      T1DM vessels is dramatically decreased whereas other copper transport proteins
      are not altered. T1DM-induced endothelial dysfunction and decrease of SOD3
      activity are rescued in transgenic mice overexpressing ATP7A. Furthermore, SOD3
      deficient T1DM mice or ATP7A mutant T1DM mice augment endothelial dysfunction and
      vascular O2(*-) production versus T1DM mice. These effects are in part due to
      hypoinsulinemia in T1DM mice, since insulin treatment, but not high glucose,
      increases ATP7A expression in VSMCs and restores SOD3 activity in the organoid
      culture of T1DM vessels. In summary, a decrease in ATP7A protein expression
      contributes to impaired SOD3 activity, resulting in O2(*-) overproduction and
      endothelial dysfunction in blood vessels of T1DM. Thus, restoring copper
      transporter function is an essential therapeutic approach for oxidant stress
      dependent vascular and metabolic diseases. 

PMID- 23884885
TI  - Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted
      metabolomics approach.
AB  - Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we
      searched for novel molecular markers that arise before and after hyperglycemia in
      a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case
      subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control
      subjects) from TwinsUK. Forty-two metabolites from three major fuel sources
      (carbohydrates, lipids, and proteins) were found to significantly correlate with
      T2D after adjusting for multiple testing; of these, 22 were previously reported
      as associated with T2D or insulin resistance. Fourteen metabolites were found to
      be associated with IFG. Among the metabolites identified, the branched-chain keto
      acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for
      IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39-1.95], P = 8.46 * 10(-9))
      and was moderately heritable (h(2) = 0.20). The association was replicated in an
      independent population (n = 720, OR 1.68 [ 1.34-2.11], P = 6.52 * 10(-6)) and
      validated in 189 twins with urine metabolomics taken at the same time as plasma
      (OR 1.87 [1.27-2.75], P = 1 * 10(-3)). Results confirm an important role for
      catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D
      IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to
      date, revealing both novel and known associated metabolites and providing
      potential novel targets for clinical prediction and a deeper understanding of
      causal mechanisms. 

PMID- 23884886
TI  - Maternal obesity induces epigenetic modifications to facilitate Zfp423 expression
      and enhance adipogenic differentiation in fetal mice.
AB  - Maternal obesity (MO) predisposes offspring to obesity and type 2 diabetes
      despite poorly defined mechanisms. Zfp423 is the key transcription factor
      committing cells to the adipogenic lineage, with exceptionally dense CpG sites in
      its promoter. We hypothesized that MO enhances adipogenic differentiation during
      fetal development through inducing epigenetic changes in the Zfp423 promoter and
      elevating its expression. Female mice were subjected to a control (Con) or
      obesogenic (OB) diet for 2 months, mated, and maintained on their diets during
      pregnancy. Fetal tissue was harvested at embryonic day 14.5 (E14.5), when the
      early adipogenic commitment is initiated. The Zfp423 expression was 3.6-fold
      higher and DNA methylation in the Zfp423 promoter was lower in OB compared with
      Con. Correspondingly, repressive histone methylation (H3K27me3) was lower in the
      Zfp423 promoter of OB fetal tissue, accompanied by reduced binding of enhancer of
      zeste 2 (EZH2). Gain- and loss-of-function analysis showed that Zfp423 regulates
      early adipogenic differentiation in fetal progenitor cells. In summary, MO
      enhanced Zfp423 expression and adipogenic differentiation during fetal
      development, at least partially through reducing DNA methylation in the Zfp423
      promoter, which is expected to durably elevate adipogenic differentiation of
      progenitor cells in adult tissue, programming adiposity and metabolic dysfunction
      later in life. 

PMID- 23884887
TI  - Human insulin resistance is associated with increased plasma levels of 12alpha
      hydroxylated bile acids.
AB  - Bile acids (BAs) exert pleiotropic metabolic effects, and physicochemical
      properties of different BAs affect their function. In rodents, insulin regulates
      BA composition, in part by regulating the BA 12alpha-hydroxylase CYP8B1. However,
      it is unclear whether a similar effect occurs in humans. To address this
      question, we examined the relationship between clamp-measured insulin sensitivity
      and plasma BA composition in a cohort of 200 healthy subjects and 35 type 2
      diabetic (T2D) patients. In healthy subjects, insulin resistance (IR) was
      associated with increased 12alpha-hydroxylated BAs (cholic acid, deoxycholic
      acid, and their conjugated forms). Furthermore, ratios of 12alpha
      hydroxylated/non-12alpha-hydroxylated BAs were associated with key features of
      IR, including higher insulin, proinsulin, glucose, glucagon, and triglyceride
      (TG) levels and lower HDL cholesterol. In T2D patients, BAs were nearly twofold
      elevated, and more hydrophobic, compared with healthy subjects, although we did
      not observe disproportionate increases in 12alpha-hydroxylated BAs. In
      multivariate analysis of the whole dataset, controlling for sex, age, BMI, and
      glucose tolerance status, higher 12alpha-hydroxy/non-12alpha-hydroxy BA ratios
      were associated with lower insulin sensitivity and higher plasma TGs. These
      findings suggest a role for 12alpha-hydroxylated BAs in metabolic abnormalities
      in the natural history of T2D and raise the possibility of developing insulin
      sensitizing therapeutics based on manipulations of BA composition. 

PMID- 23884888
TI  - beta-cell-specific IL-2 therapy increases islet Foxp3+Treg and suppresses type 1
      diabetes in NOD mice.
AB  - Interleukin-2 (IL-2) is a critical cytokine for the homeostasis and function of
      forkhead box p3-expressing regulatory T cells (Foxp3(+)Tregs). Dysregulation of
      the IL-2-IL-2 receptor axis is associated with aberrant Foxp3(+)Tregs and T cell
      mediated autoimmune diseases such as type 1 diabetes. Treatment with recombinant
      IL-2 has been reported to enhance Foxp3(+)Tregs and suppress different models of
      autoimmunity. However, efficacy of IL-2 therapy is dependent on achieving
      sufficient levels of IL-2 to boost tissue-resident Foxp3(+)Tregs while avoiding
      the potential toxic effects of systemic IL-2. With this in mind, adeno-associated
      virus (AAV) vector gene delivery was used to localize IL-2 expression to the
      islets of NOD mice. Injection of a double-stranded AAV vector encoding IL-2
      driven by a mouse insulin promoter (dsAAVmIP-IL2) increased Foxp3(+)Tregs in the
      islets but not the draining pancreatic lymph nodes. Islet Foxp3(+)Tregs in
      dsAAVmIP-IL2-treated NOD mice exhibited enhanced fitness marked by increased
      expression of Bcl-2, proliferation, and suppressor function. In contrast, ectopic
      IL-2 had no significant effect on conventional islet-infiltrating effector T
      cells. Notably, beta-cell-specific IL-2 expression suppressed late preclinical
      type 1 diabetes in NOD mice. Collectively, these findings demonstrate that beta
      cell-specific IL-2 expands an islet-resident Foxp3(+)Tregs pool that effectively
      suppresses ongoing type 1 diabetes long term. 

PMID- 23884889
TI  - Overnutrition stimulates intestinal epithelium proliferation through beta-catenin
      signaling in obese mice.
AB  - Obesity is a major risk factor for type 2 diabetes and cardiovascular diseases.
      And overnutrition is a leading cause of obesity. After most nutrients are
      ingested, they are absorbed in the small intestine. Signals from beta-catenin are
      essential to maintain development of the small intestine and homeostasis. In this
      study, we used a hyperphagia db/db obese mouse model and a high-fat diet (HFD)
      induced obesity mouse model to investigate the effects of overnutrition on
      intestinal function and beta-catenin signaling. The beta-catenin protein was
      upregulated along with inactivation of glycogen synthase kinase (GSK)-3beta in
      the intestines of both db/db and HFD mice. Proliferation of intestinal epithelial
      stem cells, villi length, nutrient absorption, and body weight also increased in
      both models. These changes were reversed by caloric restriction in db/db mice and
      by beta-catenin inhibitor JW55 (a small molecule that increases beta-catenin
      degradation) in HFD mice. Parallel, in vitro experiments showed that beta-catenin
      accumulation and cell proliferation stimulated by glucose were blocked by the
      beta-catenin inhibitor FH535. And the GSK-3 inhibitor CHIR98014 in an intestinal
      epithelial cell line increased beta-catenin accumulation and cyclin D1
      expression. These results suggested that, besides contribution to intestinal
      development and homeostasis, GSK-3beta/beta-catenin signaling plays a central
      role in intestinal morphological and functional changes in response to
      overnutrition. Manipulating the GSK-3beta/beta-catenin signaling pathway in
      intestinal epithelium might become a therapeutic intervention for obesity induced
      by overnutrition. 

PMID- 23884890
TI  - C-peptide activates AMPKalpha and prevents ROS-mediated mitochondrial fission and
      endothelial apoptosis in diabetes.
AB  - Vasculopathy is a major complication of diabetes; however, molecular mechanisms
      mediating the development of vasculopathy and potential strategies for prevention
      have not been identified. We have previously reported that C-peptide prevents
      diabetic vasculopathy by inhibiting reactive oxygen species (ROS)-mediated
      endothelial apoptosis. To gain further insight into ROS-dependent mechanism of
      diabetic vasculopathy and its prevention, we studied high glucose-induced
      cytosolic and mitochondrial ROS production and its effect on altered
      mitochondrial dynamics and apoptosis. For the therapeutic strategy, we
      investigated the vasoprotective mechanism of C-peptide against hyperglycemia
      induced endothelial damage through the AMP-activated protein kinase alpha
      (AMPKalpha) pathway using human umbilical vein endothelial cells and aorta of
      diabetic mice. High glucose (33 mmol/L) increased intracellular ROS through a
      mechanism involving interregulation between cytosolic and mitochondrial ROS
      generation. C-peptide (1 nmol/L) activation of AMPKalpha inhibited high glucose
      induced ROS generation, mitochondrial fission, mitochondrial membrane potential
      collapse, and endothelial cell apoptosis. Additionally, the AMPK activator 5
      aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside and the antihyperglycemic
      drug metformin mimicked protective effects of C-peptide. C-peptide replacement
      therapy normalized hyperglycemia-induced AMPKalpha dephosphorylation, ROS
      generation, and mitochondrial disorganization in aorta of diabetic mice. These
      findings highlight a novel mechanism by which C-peptide activates AMPKalpha and
      protects against hyperglycemia-induced vasculopathy. 

PMID- 23884891
TI  - Vascular endothelial growth factor-a and islet vascularization are necessary in
      developing, but not adult, pancreatic islets.
AB  - Pancreatic islets are highly vascularized mini-organs, and vascular endothelial
      growth factor (VEGF)-A is a critical factor in the development of islet
      vascularization. To investigate the role of VEGF-A and endothelial cells (ECs) in
      adult islets, we used complementary genetic approaches to temporally inactivate
      VEGF-A in developing mouse pancreatic and islet progenitor cells or in adult beta
      cells. Inactivation of VEGF-A early in development dramatically reduced
      pancreatic and islet vascularization, leading to reduced beta-cell proliferation
      in both developing and adult islets and, ultimately, reduced beta-cell mass and
      impaired glucose clearance. When VEGF-A was inactivated in adult beta-cells,
      islet vascularization was reduced twofold. Surprisingly, even after 3 months of
      reduced islet vascularization, islet architecture and beta-cell gene expression,
      mass, and function were preserved with only a minimal abnormality in glucose
      clearance. These data show that normal pancreatic VEGF-A expression is critical
      for the recruitment of ECs and the subsequent stimulation of endocrine cell
      proliferation during islet development. In contrast, although VEGF-A is required
      for maintaining the specialized vasculature observed in normal adult islets,
      adult beta-cells can adapt and survive long-term reductions in islet vascularity.
      These results indicate that VEGF-A and islet vascularization have a lesser role
      in adult islet function and beta-cell mass. 

PMID- 23884892
TI  - VEGF secreted by hypoxic Muller cells induces MMP-2 expression and activity in
      endothelial cells to promote retinal neovascularization in proliferative diabetic
      retinopathy.
AB  - In proliferative diabetic retinopathy (PDR), retinal ischemia promotes
      neovascularization (NV), which can lead to profound vision loss in diabetic
      patients. Treatment for PDR, panretinal photocoagulation, is inherently
      destructive and has significant visual consequences. Therapies targeting vascular
      endothelial growth factor (VEGF) have transformed the treatment of diabetic eye
      disease but have proven inadequate for treating NV, prompting exploration for
      additional therapeutic options for PDR patients. In this regard, extracellular
      proteolysis is an early and sustained activity strictly required for NV.
      Extracellular proteolysis in NV is facilitated by the dysregulated activity of
      matrix metalloproteinases (MMPs). Here, we set out to better understand the
      regulation of MMPs by ischemia in PDR. We demonstrate that accumulation of
      hypoxia-inducible factor-1alpha in Muller cells induces the expression of VEGF,
      which, in turn, promotes increased MMP-2 expression and activity in neighboring
      endothelial cells (ECs). MMP-2 expression was detected in ECs in retinal NV
      tissue from PDR patients, whereas MMP-2 protein levels were elevated in the
      aqueous of PDR patients compared with controls. Our findings demonstrate a
      complex interplay among hypoxic Muller cells, secreted angiogenic factors, and
      neighboring ECs in the regulation of MMP-2 in retinal NV and identify MMP-2 as a
      target for the treatment of PDR. 

PMID- 23884893
TI  - Antiangiogenic and antineuroinflammatory effects of kallistatin through
      interactions with the canonical Wnt pathway.
AB  - Kallistatin is a member of the serine proteinase inhibitor superfamily.
      Kallistatin levels have been shown to be decreased in the vitreous while
      increased in the circulation of patients with diabetic retinopathy (DR).
      Overactivation of the Wnt pathway is known to play pathogenic roles in DR. To
      investigate the role of kallistatin in DR and in Wnt pathway activation, we
      generated kallistatin transgenic (kallistatin-TG) mice overexpressing kallistatin
      in multiple tissues including the retina. In the oxygen-induced retinopathy (OIR)
      model, kallistatin overexpression attenuated ischemia-induced retinal
      neovascularization. In diabetic kallistatin-TG mice, kallistatin overexpression
      ameliorated retinal vascular leakage, leukostasis, and overexpression of vascular
      endothelial growth factor and intracellular adhesion molecule. Furthermore,
      kallistatin overexpression also suppressed Wnt pathway activation in the retinas
      of the OIR and diabetic models. In diabetic Wnt reporter (BAT-gal) mice,
      kallistatin overexpression suppressed retinal Wnt reporter activity. In cultured
      retinal cells, kallistatin blocked Wnt pathway activation induced by high glucose
      and by Wnt ligand. Coprecipitation and ligand-binding assays both showed that
      kallistatin binds to a Wnt coreceptor LRP6 with high affinity (Kd = 4.5 nmol/L).
      These observations suggest that kallistatin is an endogenous antagonist of LRP6
      and inhibitor of Wnt signaling. The blockade of Wnt signaling may represent a
      mechanism for its antiangiogenic and antineuroinflammatory effects. 

PMID- 23884894
TI  - Triptan safety during pregnancy: a Norwegian population registry study.
AB  - Knowledge on triptan safety during pregnancy remains limited to their class
      effect or studies on sumatriptan. Our aim was to evaluate the individual effect
      of four most frequently used triptans on several pregnancy outcomes. We used the
      Norwegian prescription database to access information on triptans redeemed by
      pregnant women living in Norway between 2004 and 2007. This database was linked
      to the Medical Birth Registry of Norway covering every institutional delivery in
      Norway and providing information on pregnancy, delivery, maternal and neonatal
      health. Estimates of associations with pregnancy outcomes were obtained by
      Generalised Estimation Equations analysis. Of the 181,125 women in our study,
      1,465 (0.8%) redeemed triptans during pregnancy, and 1,095 (0.6%) redeemed
      triptans before pregnancy only (disease comparison group). The population
      comparison group comprised the remaining 178,565 women. Using this group as
      reference, we found no associations between triptan redemption during pregnancy
      and congenital malformations. Second trimester redemption was associated with
      postpartum haemorrhage (adjusted OR 1.57; 95% CI 1.19-2.07). The disease
      comparison group had an increased risk of major congenital malformations
      (adjusted OR 1.48; 95% CI 1.11-1.97), low birth weight (adjusted OR 1.39; 95% CI
      1.08-1.81), and preterm birth (adjusted OR 1.30; 95% CI 1.06-1.60). The
      association of triptans with postpartum hemorrhage could be attributable to
      decreased platelet agreeability occurring in severe migraine. Likewise, the
      increased risk of major congenital malformations and other adverse pregnancy
      outcomes in the disease comparison group might be attributable to migraine
      severity.

PMID- 23884895
TI  - Incidental medullary thyroid microcarcinoma revealed by mild increase of
      preoperative serum calcitonin levels: therapeutic implications.
AB  - To investigate whether further, diagnostic procedures should be recommended in
      patients with slight increase of preoperative serum basal calcitonin (bCT) levels
      in whom surgical treatment can be recommendable. Fourteen consecutive patients
      with nodular thyroid disease underwent thyroidectomy in our center for suspected
      medullary thyroid microcarcinoma (MTC) because their serum bCT levels were
      slightly higher than the upper limit of normal range. Serum bCT was measured by
      radioimmunoassay, normality range = 0-20 ng/L. Surgical specimens were examined
      by the same pathologist using histologic and immunohistochemistry techniques. An
      extensive search for parafollicular C-cell hyperplasia (CCH) and/or microscopic
      MTC foci was performed. At preoperative ultrasound, a single thyroid nodule was
      depicted in three patients while a multinodular goiter in 11. The bCT values
      ranged between 24.4 and 94.6 ng/L, median 42.2 ng/L while the pentagastrin
      stimulated CT (sCT) values by pentagastrin test ranged between 61.5 and 1,262
      ng/L, median 245.0 ng/L. Total thyroidectomy was performed in 13 patients, and
      lobectomy in the other one; central node dissection was also performed in eight
      cases. At histology, MTC was diagnosed in nine patients (64.3 %), showing a
      median maximum diameter of 6.1 mm (range, 1.5-17 mm); CCH was diagnosed in the
      other five patients (35.7 %). The pentagastrin stimulation test was obtained in
      all patients. It is worth noting that a very high increase of sCT >100 ng/mL was
      observed in 5/9 patients with MTC and in 2/4 patients with HCC, therefore
      suggesting the absence of a relationship between the entity of response to
      pentagastrin test with a specific pathology (MTC vs. HCC). In six patients, the
      MTC was the nodule on which preoperative FNAC had been performed, while in other
      three patients preoperative FNAC had been performed on a different nodule from
      the MTC. Based on our experience, in case of the pentagastrin stimulation test
      with sCT <100 ng/L and a single nodule, the CT assay on FNAC may be useful,
      subsequently lobectomy with definitive histological diagnosis is recommended. In
      case of the Pg test with sCT <100 ng/L and bilateral goiter, total thyroidectomy
      with histological diagnosis is recommended. In this way, as for the surgical
      procedure, total thyroidectomy is recommended in cases of bilateral goiter, while
      lobectomy can be offered for cases with single nodes with serum dosage of bCT in
      the strict follow up. In case of the pentagastrin stimulating test with sCT <100
      ng/L and bilateral goiter, total thyroidectomy with histological diagnosis is
      recommended.

PMID- 23884896
TI  - The social and psychological impact of endometriosis on women's lives: a critical
      narrative review.
AB  - BACKGROUND Endometriosis is a chronic condition affecting between 2 and 17% of
      women of reproductive age. Common symptoms are chronic pelvic pain, fatigue,
      congestive dysmenorrhoea, heavy menstrual bleeding and deep dyspareunia. Studies
      have demonstrated the considerable negative impact of this condition on women's
      quality of life (QoL), especially in the domains of pain and psychosocial
      functioning. The impact of endometriosis is likely to be exacerbated by the
      absence of an obvious cause and the likelihood of chronic, recurring symptoms.
      The aims of this paper are to review the current body of knowledge on the social
      and psychological impact of endometriosis on women's lives; to provide insights
      into women's experience of endometriosis; to provide a critical commentary on the
      current state of knowledge and to make recommendations for future psycho-social
      research. METHODS The review draws on a method of critical narrative synthesis to
      discuss a heterogeneous range of both quantitative and qualitative studies from
      several disciplines. This included a systematic search, a structured process for
      selecting and collecting data and a systematic thematic analysis of results.
      RESULTS A total of 42 papers were included in the review; 23 used quantitative
      methods, 16 used qualitative methods and 3 were mixed methods studies. The
      majority of papers came from just four countries: UK (10), Australia (8), Brazil
      (6) and the USA (5). Key categories of impact identified in the thematic analysis
      were diagnostic delay and uncertainty; 'QoL' and everyday activities; intimate
      relationships; planning for and having children; education and work; mental
      health and emotional wellbeing and medical management and self-management.
      CONCLUSIONS Endometriosis has a significant social and psychological impact on
      the lives of women across several domains. Many studies have methodological
      limitations and there are significant gaps in the literature especially in
      relation to a consideration of the impact on partners and children. We recommend
      additional prospective and longitudinal research utilizing mixed methods
      approaches and endometriosis-specific instruments to explore the impact of
      endometriosis in more diverse populations and settings. Furthermore, there is an
      urgent need to develop and evaluate interventions for supporting women and
      partners living with this chronic and often debilitating condition. 

PMID- 23884900
TI  - Journey of patients with cancer: a systematic evaluation at tertiary care center
      in India.
AB  - In cancer patients early institution of therapy placed a very important role and
      delay in the diagnosis and treatment can cause catastrophe. Affirm step to cut
      shot this delay requires detailed information about each step of patient referral
      journey and for fulfillment of above aim, we interviewed 101 patients, to
      calculate the elapsed time at each step. Result revealed that onset of symptoms
      to median time of presentation to general practitioner is 20 (9 - 28) days, time
      consumed in state based hospital is 100 (15- 167) days while in Delhi based
      hospital is 56 (18 - 100) days. Higher cure rate (38.2%) in patients presented
      within 3 months of development of cancer symptoms than those presented late.
      Study concluded that primary physician and all the referral hospital attributed
      important role in early diagnosis and treatment of cancer.

PMID- 23884897
TI  - IVF and breast cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: The effects of controlled ovarian hyperstimulation (COH) for IVF in
      terms of breast cancer risk remain controversial, despite the hormone-dependent
      nature of the latter. METHODS: Eligible studies up to 15 February 2013 were
      identified and pooled effect estimates for relative risk (RR) were calculated
      separately for the investigations using the general population and those using
      infertile women, as a reference group. Fixed- or random-effects models were
      implemented and subgroup analyses were performed, as appropriate. RESULTS: Eight
      cohort studies were synthesized, yielding a total cohort size of 1,554,332 women
      among whom 14,961 incident breast cancer cases occurred, encompassing 576
      incident breast cancer cases among women exposed to IVF. No significant
      association between IVF and breast cancer was observed either in the group of
      studies treating the general population (RR = 0.91, 95% confidence interval (CI):
      0.74-1.11) or infertile women (RR = 1.02, 95% CI: 0.88-1.18), as a reference
      group. Of note were the marginal associations, protective for pregnant and/or
      parous women after IVF (pooled effect estimate = 0.86, 95% CI: 0.73-1.01) and
      adverse for women <30 years at first IVF treatment (pooled effect estimate =
      1.64, 95% CI: 0.96-2.80). CONCLUSIONS: At present, COH for IVF does not seem to
      impart increased breast cancer risk. Longer follow-up periods, comparisons versus
      infertile women, subgroup analyses aiming to trace vulnerable subgroups,
      adjustment for various confounders and larger informative data sets are needed
      before conclusive statements for the safety of the procedure are reached.

PMID- 23884901
TI  - A mixed methodology retrospective analysis of the learning experience of final
      year medical students attached to a 1-week intensive palliative care course based
      at an Australian university.
AB  - AIMS: To assess the experiences in an established 1-week palliative care
      placement for final year medical students attending the University of Newcastle,
      New South Wales, Australia. DESIGN: A retrospective, mixed methodology,
      consecutive cohort. Student data collected included satisfaction feedback scores,
      open-ended questions and palliative medicine multiple-choice results before and
      after their 1-week placement. RESULTS: Although there were high satisfaction
      ratings and objective improvements (P < .001) seen in multiple-choice quiz
      scores, a subset did not improve. Practical issues such as prescribing, opioid
      use, and conversions were particularly valued by students. More teaching time and
      practical experience were requested. DISCUSSION: Given the importance of
      palliative care teaching within a medical degree, the results suggest continued
      development and review of palliative medical education are essential.

PMID- 23884903
TI  - Comparative antifungal efficacy of light-activated disinfection and octenidine
      hydrochloride with contemporary endodontic irrigants.
AB  - The aim of this study was to evaluate the antifungal effects of light-activated
      disinfection (LAD) in comparison with contemporary root canal irrigation
      solutions: sodium hypochlorite and 2% chlorhexidine gluconate and a new wound
      antiseptic, octenidine hydrochloride. Seventy extracted teeth having single root
      canals were contaminated with Candida albicans for 14 days. The samples were
      divided into five experimental (n = 10) and two control (positive and negative)
      groups (n = 10): (1) LAD with toluidine blue O, (2) octenidine hydrochloride
      (OCT), (3) 2.5% sodium hypochlorite (2.5% NaOCl), (4) 5.25% sodium hypochlorite
      (5.25% NaOCl) and (5) 2% chlorhexidine. Five millilitres of each test solution
      was applied for 3 min, and irradiation time used for LAD was 30 s. After
      treatment, the dentin chips were collected from inner canal walls into vials
      containing phosphate buffered saline, vortexed, serially diluted, seeded on
      Tryptic Soy Agar plates and incubated (37  degrees C, 48 h). The number of colony
      forming units was then counted. Differences between LAD group and positive
      control group were statistically significant (P < 0.05). All Candida cells were
      totally eliminated in root canals irrigated with OCT, 2.5% NaOCl, 5.25% NaOCl and
      2% chlorhexidine groups (CFU = 0). Within the limitations of this ex vivo study,
      LAD had minimal antimicrobial effect on C. albicans when used 30 s, and further
      modifications in LAD protocol are required to improve its antifungal capability.
      A new wound antiseptic, octenidine hydrochloride, demonstrated better potential
      than LAD in elimination of Candida albicans cells and may be a promising
      alternative to NaOCl and chlorhexidine solutions in future.

PMID- 23884904
TI  - Antithrombotic therapy for improving maternal or infant health outcomes in women
      considered at risk of placental dysfunction.
AB  - BACKGROUND: Pregnancy complications such as pre-eclampsia and eclampsia,
      intrauterine growth restriction and placental abruption are thought to have a
      common origin related to abnormalities in the development and function of the
      placenta. OBJECTIVES: To compare, using the best available evidence, the benefits
      and harms of antenatal antithrombotic therapy to improve maternal or infant
      health outcomes in women considered at risk of placental dysfunction, when
      compared with other treatments, placebo or no treatment. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 July
      2012). SELECTION CRITERIA: Randomised controlled trials comparing antenatal
      antithrombotic therapy (either alone or in combination with other agents) with
      placebo or no treatment, or any other treatment in the antenatal period to
      improve maternal or infant health outcomes in women considered at risk of
      placental dysfunction. DATA COLLECTION AND ANALYSIS: Two review authors evaluated
      trials under consideration for appropriateness for inclusion and methodological
      quality without consideration of their results according to the prestated
      eligibility criteria. We used a fixed-effect meta-analysis for combining study
      data if the trials were judged to be sufficiently similar. We investigated
      heterogeneity by calculating I2 statistic, and if this indicated a high level of
      heterogeneity among the trials included, we used a random-effects model. MAIN
      RESULTS: Our search strategy identified 18 reports of 14 studies for
      consideration. The original review included five studies (484 women) which met
      the inclusion criteria, with a further five studies included in the updated
      review, involving an additional 655 women. The overall quality of the included
      trials was considered fair to good.Nine studies compared heparin (alone or in
      combination with dipyridamole or low-dose aspirin) with no treatment; and one
      compared trapidil (triazolopyrimidine).While this review identified the use of
      heparin to be associated with a statistically significant reduction in risk of
      perinatal mortality (six studies; 653 women; risk ratio (RR) 0.40; 95% confidence
      intervals (CI) 0.20 to 0.78), preterm birth before 34 (three studies; 494 women;
      RR 0.46; 95% CI 0.29 to 0.73) and 37 (five studies; 621 women; RR 0.72; 95% CI
      0.58 to 0.90) weeks' gestation, and infant birthweight below the 10th centile for
      gestational age (seven studies; 710 infants; RR 0.41; 95% CI 0.27 to 0.61), there
      is a lack of reliable information available related to clinically relevant,
      serious adverse infant health outcomes, which have not been reported to date.
      AUTHORS' CONCLUSIONS: While treatment with heparin for women considered to be at
      particularly high risk of adverse pregnancy complications secondary to placental
      insufficiency was associated with a statistically significant reduction in risk
      of perinatal mortality, preterm birth before 34 and 37 weeks' gestation, and
      infant birthweight below the 10th centile for gestational age when compared with
      no treatment for women considered at increased risk of placental dysfunction, to
      date, important information about serious adverse infant and long-term childhood
      outcomes is unavailable.

PMID- 23884902
TI  - Crystal structure of 3WJ core revealing divalent ion-promoted thermostability and
      assembly of the Phi29 hexameric motor pRNA.
AB  - The bacteriophage phi29 DNA packaging motor, one of the strongest biological
      motors characterized to date, is geared by a packaging RNA (pRNA) ring. When
      assembled from three RNA fragments, its three-way junction (3WJ) motif is highly
      thermostable, is resistant to 8 M urea, and remains associated at extremely low
      concentrations in vitro and in vivo. To elucidate the structural basis for its
      unusual stability, we solved the crystal structure of this pRNA 3WJ motif at 3.05
      A. The structure revealed two divalent metal ions that coordinate 4 nt of the RNA
      fragments. Single-molecule fluorescence resonance energy transfer (smFRET)
      analysis confirmed a structural change of 3WJ upon addition of Mg2+. The reported
      pRNA 3WJ conformation is different from a previously published construct that
      lacks the metal coordination sites. The phi29 DNA packaging motor contains a
      dodecameric connector at the vertex of the procapsid, with a central pore for DNA
      translocation. This portal connector serves as the foothold for pRNA binding to
      procapsid. Subsequent modeling of a connector/pRNA complex suggests that the pRNA
      of the phi29 DNA packaging motor exists as a hexameric complex serving as a
      sheath over the connector. The model of hexameric pRNA on the connector agrees
      with AFM images of the phi29 pRNA hexamer acquired in air and matches all
      distance parameters obtained from cross-linking, complementary modification, and
      chemical modification interference.

PMID- 23884905
TI  - A real-time system for biomechanical analysis of human movement and muscle
      function.
AB  - Mechanical analysis of movement plays an important role in clinical management of
      neurological and orthopedic conditions. There has been increasing interest in
      performing movement analysis in real-time, to provide immediate feedback to both
      therapist and patient. However, such work to date has been limited to single
      joint kinematics and kinetics. Here we present a software system, named human
      body model (HBM), to compute joint kinematics and kinetics for a full body model
      with 44 degrees of freedom, in real-time, and to estimate length changes and
      forces in 300 muscle elements. HBM was used to analyze lower extremity function
      during gait in 12 able-bodied subjects. Processing speed exceeded 120 samples per
      second on standard PC hardware. Joint angles and moments were consistent within
      the group, and consistent with other studies in the literature. Estimated muscle
      force patterns were consistent among subjects and agreed qualitatively with
      electromyography, to the extent that can be expected from a biomechanical model.
      The real-time analysis was integrated into the D-Flow system for development of
      custom real-time feedback applications and into the gait real-time analysis
      interactive lab system for gait analysis and gait retraining. 

PMID- 23884906
TI  - Rates and characteristics of sleep paralysis in the general population of Denmark
      and Egypt.
AB  - In the current research we report data from two studies that examined rates and
      characteristics of sleep paralysis (SP) in the general population of Denmark and
      Egypt. In Study I, individuals from Denmark and Egypt did not differ in age
      whereas there were more males in the Egyptian sample (47 vs. 64 %); in Study II,
      individuals from Denmark and Egypt were comparable in terms of age and gender
      distribution. In Study I we found that significantly fewer individuals had
      experienced SP in Denmark [25 % (56/223)] than in Egypt [44 % (207/470)] p <
      .001. In Study II we found that individuals who had experienced at least one
      lifetime episode of SP from Denmark (n = 58) as compared to those from Egypt (n =
      143) reported significantly fewer SP episodes in a lifetime relative to SP
      experiencers from Egypt (M = 6.0 vs. M = 19.4, p < .001). SP in the Egyptian
      sample was characterized by high rates of SP (as compared to in Denmark),
      frequent occurrences (three times that in the Denmark sample), prolonged
      immobility during SP, and great fear of dying from the experience. In addition,
      in Egypt, believing SP to be precipitated by the supernatural was associated with
      fear of the experience and longer SP immobility. Findings are discussed in the
      context of cultural elaboration and salience theories of SP.

PMID- 23884907
TI  - Cardiac MRI: diagnostic gain of an additional axial SSFP chest sequence for the
      detection of potentially significant extracardiac findings in the cardiac MRI
      examination setting.
AB  - PURPOSE: Cardiac MRI (CMRI) is an effective method for imaging of the heart. The
      aim of our study was to assess whether an axial chest sequence in addition to the
      standard CMR examination setting has advantages in the detection of potentially
      significant extracardiac findings (PSEF). MATERIALS AND METHODS: 400 consecutive
      patients were imaged at 1.5 T for clinical reasons. In addition to the standard
      long and short-axis views, an axial SSFP sequence was obtained covering the
      thorax from the lung apex to the diaphragm. All sequences were separately
      evaluated for PSEF. RESULTS: A total of 25 PSEF were diagnosed in 400 patients,
      including 16 pleural effusions, a pulmonary fibrosis, a spondylodiscitis,
      ascites, lymphadenopathies, relapse of a mamma carcinoma, growth of adrenal
      glands metastases and diaphragmatic elevation. All 25 PSEF were detected by
      reading survey sequences. 24 of the 25 PSEF were detected by the additional SSFP
      chest sequence as well as the CINE sequences. CONCLUSION: In our study the
      additional axial SSFP chest sequence didn't show a benefit in the detection of
      PSEF. With the survey sequences we were able to detect all PSEF. We conclude that
      survey images should be assessed for additional findings.

PMID- 23884908
TI  - MR-guided HIFU treatment of symptomatic uterine fibroids using novel feedback
      regulated volumetric ablation: effectiveness and clinical practice.
AB  - PURPOSE: To evaluate a novel feedback-regulated volumetric sonication method in
      MR-guided HIFU treatment of symptomatic uterine fibroids. MATERIALS AND METHODS:
      27 fibroids with an average volume of 124.9 +/- 139.8 cc in 18 women with
      symptomatic uterine fibroids were ablated using the new HIFU system Sonalleve
      (1.5 T MR system Achieva, Philips). 21 myomas in 13 women were reevaluated 6
      months later. Standard (treatment) cells (TC) and feedback-regulated (feedback)
      cells (FC) with a diameter of 4, 8, 12, and 16 mm were used and compared
      concerning sonication success, diameter of induced necrosis, and maximum achieved
      temperature. The non-perfused volume ratio (NPV related to myoma volume) was
      quantified. The fibroid volume was measured before, 1 month, and 6 months after
      therapy. Symptoms were quantified using a specific questionnaire (UFS-QoL).
      RESULTS: In total, 205 TC and 227 FC were applied. The NPV ratio was 23 +/- 15 %
      (2 - 55). The TC were slightly smaller than intended (-3.9 +/- 52 %; range, -100 
      81), while the FC were 20.1 +/- 25.3 % bigger (p = 0.02). Feedback mechanism is
      less diversifying in diameter (p < 0.001). Overall, the FC correlate well with
      the planned treatment diameter (r = 0.79), other than the TC (r = 0.38). Six
      months after therapy, the fibroid volume was reduced by 45 +/- 21 % (5 - 100) (p
      = 0.001). The symptoms decreased significantly (p = 0.001). No serious adverse
      events were recorded. CONCLUSION: Use of volumetric sonication leads to
      homogenous heating and sufficient necrosis. It is a safe and effective therapy
      for treating symptomatic uterine fibroids. Successful sonication of feedback
      cells leads to more contiguous necrosis in diameter and a less diversifying
      temperature. KEY POINTS: ? MR-guided HIFU ablation of symptomatic uterine
      fibroids is a valuable treatment option. ? By non-invasive HIFU fibroid volumes
      can be reduced and symptoms improved. ? The novel feedback-regulated treatment
      cells offer advantages over standard treatment cells.

PMID- 23884909
TI  - Quantification of pulmonary perfusion with free-breathing dynamic contrast
      enhanced MRI--a pilot study in healthy volunteers.
AB  - PURPOSE: The assessment of pulmonary perfusion using dynamic contrast-enhanced
      (DCE) MRI is still limited in the clinical routine due to the necessity of breath
      holding. An acquisition technique for the quantitative assessment of pulmonary
      perfusion in free breathing was investigated in our study. MATERIALS AND METHODS:
      10 healthy male volunteers underwent pulmonary DCE-MRI on a 1.5 T scanner. Each
      volunteer was examined twice: (a) in breath-hold half expiration and (b) during
      shallow free breathing. The pulmonary parenchyma was segmented automatically. The
      pulmonary plasma flow (PPF) and pulmonary plasma volume (PPV) were determined
      pixel-wise using a one-compartment model. RESULTS: All examinations were of
      diagnostic image quality. The measured mean values of the PPV were significantly
      lower in the breath-hold technique than during free breathing ((10.2 +/- 2.8)
      ml/100 ml vs. (12.7 +/- 3.9) ml/100 ml); p < 0.05). A significant difference was
      also observed between both PPF measurements (mean PPF (206.2 +/- 104.0) ml/100
      ml/min in breath-hold technique vs. (240.6 +/- 114.0) ml/100 ml/min during free
      breathing; p < 0.05). CONCLUSION: Free-breathing DCE-MRI appears to be suitable
      for the quantitative assessment of the pulmonary perfusion in healthy volunteers.
      The proposed segmentation and quantification approach does not suffer from the
      increased motion, as compared to the breath-holding measurement. The increased
      PPV and PPF during free breathing are in accordance with the results of previous
      studies concerning breathing influence on perfusion parameters. Overall, free
      breathing DCE-MRI may be a promising technique for the assessment of pulmonary
      perfusion in various pathologies.

PMID- 23884910
TI  - Akt SUMOylation regulates cell proliferation and tumorigenesis.
AB  - Proto-oncogene Akt plays essential roles in cell proliferation and tumorigenesis.
      Full activation of Akt is regulated by phosphorylation, ubiquitination, and
      acetylation. Here we report that SUMOylation of Akt is a novel mechanism for its
      activation. Systematically analyzing the role of lysine residues in Akt
      activation revealed that K276, which is located in a SUMOylation consensus motif,
      is essential for Akt activation. Ectopic or endogenous Akt1 could be modified by
      SUMOylation. RNA interference-mediated silencing of UBC9 reduced Akt SUMOylation,
      which was promoted by SUMO E3 ligase PIAS1 and reversed by the SUMO-specific
      protease SENP1. Although multiple sites on Akt could be SUMOylated, K276 was
      identified as a major SUMO acceptor site. K276R or E278A mutation reduced
      SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these
      mutations also completely abolished Akt kinase activity. In support of these
      results, we found that expression of PIAS1 and SUMO1 increased Akt activity,
      whereas expression of SENP1 reduced Akt1 activity. Interestingly, the cancer
      derived mutant E17K in Akt1 that occurs in various cancers was more efficiently
      SUMOylated than wild-type Akt. Moreover, SUMOylation loss dramatically reduced
      Akt1 E17K-mediated cell proliferation, cell migration, and tumorigenesis.
      Collectively, our findings establish that Akt SUMOylation provides a novel
      regulatory mechanism for activating Akt function.

PMID- 23884911
TI  - Angiotensin-(1-9) enhances stasis-induced venous thrombosis in the rat because of
      the impairment of fibrinolysis.
AB  - INTRODUCTION: ACE2 alternatively converts angiotensin (Ang) II into Ang-(1-7) and
      Ang I into Ang-(1-9). There is little information in the literature with respect
      to Ang-(1-9) properties. A number of studies show a link between peptides of the
      renin-angiotensin system and thrombosis. MATERIALS AND METHODS: We have
      investigated the influence of Ang-(1-9) on stasis-induced venous thrombosis in
      the rat. The contribution of coagulation and fibrinolytic systems, angiotensin
      receptor type 1 (AT1) and MAS receptor in the mode of Ang-(1-9) action was also
      determined. RESULTS: Ang-(1-9) enhanced thrombosis development, decreased plasma
      concentration of tissue plasminogen activator and increased the level of its
      inhibitor (PAI-1). The action of Ang-(1-9) was reversed by selective antagonist
      of AT1 receptor, but not Ang-(1-7) antagonist. Ang-(1-9) did not bind to the AT1
      receptor. CONCLUSIONS: Ang-(1-9) enhances venous thrombosis in the rat because of
      the impairment of fibrinolysis. The prothrombotic effect of Ang-(1-9) is mediated
      by Ang II acting via the AT1 receptor.

PMID- 23884912
TI  - Serum angiotensin-converting enzyme level as a marker of severity in HBeAg
      negative chronic hepatitis B virus infection.

PMID- 23884913
TI  - Residue levels of organochlorine pesticides in some ecosystem components of
      Manzala Lake.
AB  - To evaluate the organochlorine pesticide (OCP) contamination of Manzala Lake, its
      ecosystem was investigated during the winter season (December to March). The
      studied ecosystem components were water, sediment, aquatic weeds, and fishes in
      four locations. The samples were analyzed by gas chromatography with electron
      capture detector. Pollutant levels of total OCPs showed significantly high levels
      in the water areas of Round road (46.253 ng/ml), Port-Said Damietta road (19.301
      ng/ml), followed by Bughas El-Rasoah (5.539 ng/ml), then Ashtoum El Gamel
      (natural reserve area now) (0.289 ng/ml). Organochlorines were detected in
      sediment only in Round road (3.359 MUg/kg) and Port-Said Damietta road (0.171
      MUg/kg) by significant order while they were undetectable in Ashtoum El Gamel and
      Bughas El-Rasoah. Total OCPs in aquatic weeds ranged between 0.194 MUg/kg in Port
      Said Damietta and 0.026 MUg/kg in Ashtoum El Gamel. While OCPs were 0.160 and
      0.153 MUg/kg in Round road and Bughas El-Rasoah, respectively. Concerning fish
      muscles OCPs were significantly higher in the Round road area (0.397 MUg/kg)
      followed by the Port-Said Damietta road (0.258 MUg/kg), and finally, Ashtoum El
      Gamel samples (0.126 MUg/kg). The results revealed the direct relation for the
      accumulation of OCPs between studied ecosystem parameters at the Manzala Lake
      during the winter season. Results also demonstrated that fish samples collected
      from the Manzala Lake in the studied areas were contaminated with levels of
      organochlorines, not higher than the maximum permissible level recorded by
      FAO/WHO, and that the public is not at risk with fish consumption.

PMID- 23884914
TI  - Governmental policies drive the LUCC trajectories in the Jianghan Plain.
AB  - The prosperity of farmers is closely tied to governmental policies. The Jianghan
      Plain is an important region for commodity grains, cotton and edible oil for
      China. The trajectories of land use and land cover change (LUCC) of the study
      area from 1995 to 2010 were studied based on the LUCC database of the Chinese
      Academy of Sciences. The LUCC was characterised by a continuous decrease of
      arable land and continuous increase of waters and construction land. The LUCC was
      obviously concurrent with the implementation of related national policies. The
      transition to construction land was ever well controlled by 'Notice regarding the
      further strengthening of land management and arable land protection' promulgated
      in 1997. However, it flourished again with the 'Rise of Central China Strategy'
      taking effect since 2006. The transition of construction land to others reflects
      an uncommon trend, which must be strengthened with the strict implementation of
      the overall plan, which imposes a limited acreage quota of construction land to
      each district. The policies were quite contradictory to the transition of waters.
      LUCC related to waters is most active, which was driven by both natural forces
      and national policies. Just after the devastating flood of 1998, the state
      council of China put forward the Green Policy to govern the major rivers. As to
      the study area, it is mainly to 'push over dykes to let flood through and return
      farmland to lakes'. In 2004, the Grain Direct Subsidy Policy was implemented,
      which, along with the surge in the price of rice, resulted in a strengthening
      trend of conversion of ponds to paddy fields. 

PMID- 23884915
TI  - Oral and intravenous thyroxine (T4) achieve comparable serum levels for hormonal
      resuscitation protocol in organ donors: a randomized double-blinded study.
AB  - BACKGROUND: Thyroxine (T4) administration is advocated in the management of organ
      donors; however, the bioavailability of oral thyroxine is unknown in this patient
      population. OBJECTIVE: The primary objective of this study was to compare the
      percentage of the study time (from study drug administration to organ
      procurement) that patients in the oral vs the intravenous group required
      inotropic support. Secondary objectives included plasma levels of T3 and T4 and
      number of organs donated following oral vs intravenous T4 administration. DESIGN:
      Randomized double-blinded study. SETTING: Adult medical-surgical intensive care
      unit. PATIENTS: Thirty-two adult solid organ donors. INTERVENTIONS: Patients were
      randomized to receive either an oral or intravenous dose of T4 (2 MUg.kg-1). All
      patients received an oral and intravenous study drug preparation, one of which
      was a placebo. The study was double-blinded, and randomization occurred in blocks
      of four and six. MEASUREMENTS: The number and duration of inotropic/vasopressor
      therapies and free serum levels of T3 and T4 were determined hourly until
      procurement. MAIN RESULTS: Following T4 administration, all patients remained on
      inotropic/vasopressor therapy for the same mean (SD) duration [93 (3)%] of the
      study period. There was a similar and gradual decrease in the number and dosages
      of inotropes/vasopressors required in both groups. There was no difference in T3
      or T4 levels between groups. Oral bioavailability of T4 was 93% of the
      intravenous group at six hours and 91% overall. At six hours, the mean area under
      the curve for T4 was similar between the intravenous group [92.2 (33); 95%
      confidence interval (CI) 76 to 108.4] and the oral group [86.1 (14); 95% CI 79.4
      to 92.8]. CONCLUSIONS: Orally administered T4 is well absorbed and achieves a
      bioavailability of approximately 91-93% of intravenous T4 in organ donors.
      Inotropic/vasopressor requirements and hemodynamic responses following oral or
      intravenous thyroxine administration were comparable. Oral T4 is suitable for
      hormonal therapy for organ donors. This trial was registered at
      www.clinicaltrials.gov : NCT00238030.

PMID- 23884916
TI  - American Academy of Audiology response to Gurgel et al.

PMID- 23884917
TI  - Reply to Dr Carlson's letter: A new standardized format for reporting hearing
      outcome in clinical trials.

PMID- 23884918
TI  - Re: "A new standardized format for reporting hearing outcome in clinical trials".

PMID- 23884919
TI  - Letter to the editor response--Entong Wang.

PMID- 23884920
TI  - Atrial fibrillation in athletes and the interplay between exercise and health.

PMID- 23884921
TI  - Giant clear cell renal carcinoma extended from the kidney until the pulmonary
      artery.

PMID- 23884922
TI  - Why public dissemination of science matters: a manifesto.
AB  - Communicating science to the public takes time away from busy research careers.
      So why would you do it? I here offer six reasons. First, we owe that
      understanding to the people who fund our experiments, the taxpaying public.
      Second, we can leverage our skills as scientists to inspire critical thinking in
      public and political dialog. Third, researchers are optimally positioned to stem
      the flow of scientific misinformation in the media. Fourth, we can explain the
      ways and the means by which science can (and cannot) improve law and social
      policy. Fifth, it is incumbent upon us to explain what science is and is not:
      while it is a way of thinking that upgrades our intuitions, it also comes with a
      deep understanding of (and tolerance for) uncertainty. Finally, we find ourselves
      in the pleasurable position of being able to share the raw beauty of the world
      around us-and in the case of neuroscience, the world inside us. I suggest that
      scientists are optimally stationed to increase their presence in the public
      sphere: our training positions us to synthesize large bodies of data, weigh the
      evidence, and communicate with nuance, sincerity and exactitude. 

PMID- 23884923
TI  - The countermanding task revisited: mimicry of race models.

PMID- 23884924
TI  - How working memory training improves emotion regulation: neural efficiency,
      effort, and transfer effects.

PMID- 23884925
TI  - Emergence of adaptive computation by single neurons in the developing cortex.
AB  - Adaptation is a fundamental computational motif in neural processing. To maintain
      stable perception in the face of rapidly shifting input, neural systems must
      extract relevant information from background fluctuations under many different
      contexts. Many neural systems are able to adjust their input-output properties
      such that an input's ability to trigger a response depends on the size of that
      input relative to its local statistical context. This "gain-scaling" strategy has
      been shown to be an efficient coding strategy. We report here that this property
      emerges during early development as an intrinsic property of single neurons in
      mouse sensorimotor cortex, coinciding with the disappearance of spontaneous waves
      of network activity, and can be modulated by changing the balance of spike
      generating currents. Simultaneously, developing neurons move toward a common
      intrinsic operating point and a stable ratio of spike-generating currents. This
      developmental trajectory occurs in the absence of sensory input or spontaneous
      network activity. Through a combination of electrophysiology and modeling, we
      demonstrate that developing cortical neurons develop the ability to perform
      nearly perfect gain scaling by virtue of the maturing spike-generating currents
      alone. We use reduced single neuron models to identify the conditions for this
      property to hold. 

PMID- 23884927
TI  - Type 1 inositol trisphosphate receptor regulates cerebellar circuits by
      maintaining the spine morphology of purkinje cells in adult mice.
AB  - The structural maintenance of neural circuits is critical for higher brain
      functions in adulthood. Although several molecules have been identified as
      regulators for spine maintenance in hippocampal and cortical neurons, it is
      poorly understood how Purkinje cell (PC) spines are maintained in the mature
      cerebellum. Here we show that the calcium channel type 1 inositol trisphosphate
      receptor (IP3R1) in PCs plays a crucial role in controlling the maintenance of
      parallel fiber (PF)-PC synaptic circuits in the mature cerebellum in vivo.
      Significantly, adult mice lacking IP3R1 specifically in PCs (L7
      Cre;Itpr1(flox/flox)) showed dramatic increase in spine density and spine length
      of PCs, despite having normal spines during development. In addition, the
      abnormally rearranged PF-PC synaptic circuits in mature cerebellum caused
      unexpectedly severe ataxia in adult L7-Cre;Itpr1(flox/flox) mice. Our findings
      reveal a specific role for IP3R1 in PCs not only as an intracellular mediator of
      cerebellar synaptic plasticity induction, but also as a critical regulator of PF
      PC synaptic circuit maintenance in the mature cerebellum in vivo; this mechanism
      may underlie motor coordination and learning in adults. 

PMID- 23884926
TI  - Fascin regulates the migration of subventricular zone-derived neuroblasts in the
      postnatal brain.
AB  - After birth, stem cells in the subventricular zone (SVZ) generate neuroblasts
      that migrate along the rostral migratory stream (RMS) to become interneurons in
      the olfactory bulb (OB). This migration is a fundamental event controlling the
      proper integration of new neurons in a pre-existing synaptic network. Many
      regulators of neuroblast migration have been identified; however, still very
      little is known about the intracellular molecular mechanisms controlling this
      process. Here, we show that the actin-bundling protein fascin is highly
      upregulated in mouse SVZ-derived migratory neuroblasts. Fascin-1ko mice display
      an abnormal RMS and a smaller OB. Bromodeoxyuridine labeling experiments show
      that lack of fascin significantly impairs neuroblast migration, but does not
      appear to affect cell proliferation. Moreover, fascin depletion substantially
      alters the polarized morphology of rat neuroblasts. Protein kinase C (PKC)
      dependent phosphorylation of fascin on Ser39 regulates its actin-bundling
      activity. In vivo postnatal electroporation of phosphomimetic (S39D) or
      nonphosphorylatable (S39A) fascin variants followed by time-lapse imaging of
      brain slices demonstrates that the phospho-dependent modulation of fascin
      activity ensures efficient neuroblast migration. Finally, fluorescence lifetime
      imaging microscopy studies in rat neuroblasts reveal that the interaction between
      fascin and PKC can be modulated by cannabinoid signaling, which controls
      neuroblast migration in vivo. We conclude that fascin, whose upregulation appears
      to mark the transition to the migratory neuroblast stage, is a crucial regulator
      of neuroblast motility. We propose that a tightly regulated phospho/dephospho
      fascin cycle modulated by extracellular signals is required for the polarized
      morphology and migration in neuroblasts, thus contributing to efficient
      neurogenesis. 

PMID- 23884928
TI  - Lhx2 balances progenitor maintenance with neurogenic output and promotes
      competence state progression in the developing retina.
AB  - The LIM-Homeodomain transcription factor Lhx2 is an essential organizer of early
      eye development and is subsequently expressed in retinal progenitor cells (RPCs).
      To determine its requirement in RPCs, we performed a temporal series of
      conditional inactivations in mice with the early RPC driver Pax6 alpha-Cre and
      the tamoxifen-inducible Hes1(CreERT2) driver. Deletion of Lhx2 caused a
      significant reduction of the progenitor population and a corresponding increase
      in neurogenesis. Precursor fate choice correlated with the time of inactivation;
      early and late inactivation led to the overproduction of retinal ganglion cells
      (RGCs) and rod photoreceptors, respectively. In each case, however, the
      overproduction was selective, occurring at the expense of other cell types and
      indicating a role for Lhx2 in generating cell type diversity. RPCs that persisted
      in the absence of Lhx2 continued to generate RGC precursors beyond their normal
      production window, suggesting that Lhx2 facilitates a transition in competence
      state. These results identify Lhx2 as a key regulator of RPC properties that
      contribute to the ordered production of multiple cell types during retinal tissue
      formation. 

PMID- 23884929
TI  - Olfactory functions scale with circuit restoration in a rapidly reversible
      Alzheimer's disease model.
AB  - Neural circuits maintain a precise organization that is vital for normal brain
      functions and behaviors, but become disrupted during neurological disease.
      Understanding the connection between wiring accuracy and function to measure
      disease progression or recovery has been difficult because of the complexity of
      behavioral circuits. The olfactory system maintains well-defined neural
      connections that regenerate throughout life. We previously established a
      reversible in vivo model of Alzheimer's disease by overexpressing a humanized
      mutated amyloid precursor protein (hAPP) in olfactory sensory neurons (OSNs).
      Using this model, we currently show that hAPP is present in the OSN axons of
      mutant mice, which exhibit strong caspase3 signal and reduced synaptic protein
      expression by 3 weeks of age. In the olfactory bulb, we show that glomerular
      structure is distorted and OSN axonal convergence is lost. In vivo functional
      imaging experiments further demonstrate disruption of the glomerular circuitry,
      and behavioral assays reveal that olfactory function is significantly impaired.
      Because OSNs regenerate, we also tested if the system could recover from hAPP
      induced disruption. We found that after 1 or 3 weeks of shutting-off hAPP
      expression, the glomerular circuit was partially restored both anatomically and
      functionally, with behavioral deficits similarly reversed. Interestingly, the
      degree of functional recovery tracked directly with circuit restoration.
      Together, these data demonstrate that hAPP-induced circuit disruption and
      subsequent recovery can occur rapidly and that behavior can provide a measure of
      circuit organization. Thus, olfaction may serve as a useful biomarker to both
      follow disease progression and gauge potential recovery. 

PMID- 23884930
TI  - Developmental changes in structural and functional properties of hippocampal
      AMPARs parallels the emergence of deliberative spatial navigation in juvenile
      rats.
AB  - The neural mechanisms that support the late postnatal development of spatial
      navigation are currently unknown. We investigated this in rats and found that an
      increase in the duration of AMPAR-mediated synaptic responses in the hippocampus
      was related to the emergence of spatial navigation. More specifically,
      spontaneous alternation rate, a behavioral indicator of hippocampal integrity,
      increased at the end of the third postnatal week in association with increases in
      AMPAR response duration at SC-CA1 synapses and synaptically driven postsynaptic
      discharge of CA1 pyramidal neurons. Pharmacological prolongation of glutamatergic
      synaptic transmission in juveniles increased the spontaneous alternation rate and
      CA1 postsynaptic discharge and reduced the threshold for the induction of
      activity-dependent synaptic plasticity at SC-CA1 synapses. A decrease in GluA1
      and increases in GluA3 subunit and transmembrane AMPAR regulatory protein (TARP)
      expression at the end of the third postnatal week provide a molecular explanation
      for the increase in AMPAR response duration and reduced efficacy of AMPAR
      modulators with increasing age. A shift in the composition of AMPARs and
      increased association with AMPAR protein complex accessory proteins at the end of
      the third postnatal week likely "turns on" the hippocampus by increasing AMPAR
      response duration and postsynaptic excitability and reducing the threshold for
      activity-dependent synaptic potentiation. 

PMID- 23884931
TI  - Neuronal Rac1 is required for learning-evoked neurogenesis.
AB  - Hippocampus-dependent learning and memory relies on synaptic plasticity as well
      as network adaptations provided by the addition of adult-born neurons. We have
      previously shown that activity-induced intracellular signaling through the Rho
      family small GTPase Rac1 is necessary in forebrain projection neurons for normal
      synaptic plasticity in vivo, and here we show that selective loss of neuronal
      Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse
      hippocampus. Earlier work has indicated that experience elevates the abundance of
      adult-born neurons in the hippocampus primarily by enhancing the survival of
      neurons produced just before the learning event. Loss of Rac1 in mature
      projection neurons did reduce learning-evoked neurogenesis but, contrary to our
      expectations, these effects were not mediated by altering the survival of young
      neurons in the hippocampus. Instead, loss of neuronal Rac1 activation selectively
      impaired a learning-evoked increase in the proliferation and accumulation of
      neural precursors generated during the learning event itself. This indicates that
      experience-induced alterations in neurogenesis can be mechanistically resolved
      into two effects: (1) the well documented but Rac1-independent signaling cascade
      that enhances the survival of young postmitotic neurons; and (2) a previously
      unrecognized Rac1-dependent signaling cascade that stimulates the proliferative
      production and retention of new neurons generated during learning itself. 

PMID- 23884932
TI  - Slit/Robo signaling mediates spatial positioning of spiral ganglion neurons
      during development of cochlear innervation.
AB  - During the development of periphery auditory circuits, spiral ganglion neurons
      (SGNs) extend their neurites to innervate cochlear hair cells (HCs) with their
      soma aggregated into a cluster spatially segregated from the cochlear sensory
      epithelium. The molecular mechanisms underlying this spatial patterning remain
      unclear. In this study, in situ hybridization in the mouse cochlea suggests that
      Slit2 and its receptor, Robo1/2, exhibit apparently complementary expression
      patterns in the spiral ganglion and its nearby region, the spiral limbus. In
      Slit2 and Robo1/2 mutants, the spatial restriction of SGNs was disrupted.
      Mispositioned SGNs were found to scatter in the space between the cochlear
      epithelium and the main body of spiral ganglion, and the neurites of
      mispositioned SGNs were misrouted and failed to innervate HCs. Furthermore, in
      Robo1/2 mutants, SGNs were displaced toward the cochlear epithelium as an
      entirety. Examination of different embryonic stages in the mutants revealed that
      the mispositioning of SGNs was due to a progressive displacement to ectopic
      locations after their initial normal settlement at an earlier stage. Our results
      suggest that Slit/Robo signaling imposes a restriction force on SGNs to ensure
      their precise positioning for correct SGN-HC innervations. 

PMID- 23884933
TI  - The organization of dorsal frontal cortex in humans and macaques.
AB  - The human dorsal frontal cortex has been associated with the most sophisticated
      aspects of cognition, including those that are thought to be especially refined
      in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI)
      and functional MRI (fMRI) in humans and macaques to infer and compare the
      organization of dorsal frontal cortex in the two species. Using DW-MRI
      tractography-based parcellation, we identified 10 dorsal frontal regions lying
      between the human inferior frontal sulcus and cingulate cortex. Patterns of
      functional coupling between each area and the rest of the brain were then
      estimated with fMRI and compared with functional coupling patterns in macaques.
      Areas in human medial frontal cortex, including areas associated with high-level
      social cognitive processes such as theory of mind, showed a surprising degree of
      similarity in their functional coupling patterns with the frontal pole, medial
      prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find
      evidence for "new" regions in human medial frontal cortex. On the lateral
      surface, comparison of functional coupling patterns suggested correspondences in
      anatomical organization distinct from those that are widely assumed. A human
      region sometimes referred to as lateral frontal pole more closely resembled area
      46, rather than the frontal pole, of the macaque. Overall the pattern of results
      suggest important similarities in frontal cortex organization in humans and other
      primates, even in the case of regions thought to carry out uniquely human
      functions. The patterns of interspecies correspondences are not, however, always
      those that are widely assumed. 

PMID- 23884934
TI  - CLHM-1 is a functionally conserved and conditionally toxic Ca2+-permeable ion
      channel in Caenorhabditis elegans.
AB  - Disruption of neuronal Ca(2+) homeostasis contributes to neurodegenerative
      diseases through mechanisms that are not fully understood. A polymorphism in
      CALHM1, a recently described ion channel that regulates intracellular Ca(2+)
      levels, is a possible risk factor for late-onset Alzheimer's disease. Since there
      are six potentially redundant CALHM family members in humans, the physiological
      and pathophysiological consequences of CALHM1 function in vivo remain unclear.
      The nematode Caenorhabditis elegans expresses a single CALHM1 homolog, CLHM-1.
      Here we find that CLHM-1 is expressed at the plasma membrane of sensory neurons
      and muscles. Like human CALHM1, C. elegans CLHM-1 is a Ca(2+)-permeable ion
      channel regulated by voltage and extracellular Ca(2+). Loss of clhm-1 in the body
      wall muscles disrupts locomotory kinematics and biomechanics, demonstrating that
      CLHM-1 has a physiologically significant role in vivo. The motility defects
      observed in clhm-1 mutant animals can be rescued by muscle-specific expression of
      either C. elegans CLHM-1 or human CALHM1, suggesting that the function of these
      proteins is conserved in vivo. Overexpression of either C. elegans CLHM-1 or
      human CALHM1 in neurons is toxic, causing degeneration through a necrotic-like
      mechanism that is partially Ca(2+) dependent. Our data show that CLHM-1 is a
      functionally conserved ion channel that plays an important but potentially toxic
      role in excitable cell function. 

PMID- 23884935
TI  - The membrane-active tri-block copolymer pluronic F-68 profoundly rescues rat
      hippocampal neurons from oxygen-glucose deprivation-induced death through early
      inhibition of apoptosis.
AB  - Pluronic F-68, an 80% hydrophilic member of the Pluronic family of polyethylene
      polypropylene-polyethylene tri-block copolymers, protects non-neuronal cells from
      traumatic injuries and rescues hippocampal neurons from excitotoxic and oxidative
      insults. F-68 interacts directly with lipid membranes and restores membrane
      function after direct membrane damage. Here, we demonstrate the efficacy of
      Pluronic F-68 in rescuing rat hippocampal neurons from apoptosis after oxygen
      glucose deprivation (OGD). OGD progressively decreased neuronal survival over 48
      h in a severity-dependent manner, the majority of cell death occurring after 12 h
      after OGD. Administration of F-68 for 48 h after OGD rescued neurons from death
      in a dose-dependent manner. At its optimal concentration (30 MUm), F-68 rescued
      all neurons that would have died after the first hour after OGD. This level of
      rescue persisted when F-68 administration was delayed 12 h after OGD. F-68 did
      not alter electrophysiological parameters controlling excitability, NMDA receptor
      activated currents, or NMDA-induced increases in cytosolic calcium
      concentrations. However, F-68 treatment prevented phosphatidylserine
      externalization, caspase activation, loss of mitochondrial membrane potential,
      and BAX translocation to mitochondria, indicating that F-68 alters apoptotic
      mechanisms early in the intrinsic pathway of apoptosis. The profound neuronal
      rescue provided by F-68 after OGD and the high level of efficacy with delayed
      administration indicate that Pluronic copolymers may provide a novel, membrane
      targeted approach to rescuing neurons after brain ischemia. The ability of
      membrane-active agents to block apoptosis suggests that membranes or their lipid
      components play prominent roles in injury-induced apoptosis. 

PMID- 23884936
TI  - An increase in the association of GluN2B containing NMDA receptors with membrane
      scaffolding proteins was related to memory declines during aging.
AB  - The NMDA receptor is an important component of spatial working and reference
      memory. The receptor is a heterotetramer composed of a family of related
      subunits. The GluN2B subunit of the NMDA receptor appears to be essential for
      some forms of memory and is particularly vulnerable to change with age in both
      the hippocampus and cerebral cortex. GluN2B expression is particularly reduced in
      frontal cortex synaptic membranes. The current study examined the relationship
      between spatial cognition and protein-protein interactions of GluN2B-containing
      NMDA receptors in frontal cortex crude synaptosome from 3, 12, and 26-month-old
      C57BL/6 mice. Aged mice showed a significant decline in spatial reference memory
      and reversal learning from both young and middle-aged mice. Coimmunoprecipitation
      of GluN2B subunits revealed an age-related increase in the ratio of both
      postsynaptic density-95 (PSD-95) and the GluN2A subunit to the GluN2B subunit.
      Higher ratios of PSD-95/GluN2B and GAIP-interacting protein C-terminus
      (GIPC)/GluN2B were associated with poorer learning index scores across all ages.
      There was a significant correlation between GIPC/GluN2B and PSD-95/GluN2B ratios,
      but PSD-95/GluN2B and GluN2A/GluN2B ratios did not show a relationship. These
      results suggest that there were more triheteromeric (GluN2B/GluN2A/GluN1) NMDA
      receptors in older mice than in young adults, but this did not appear to impact
      spatial reference memory. Instead, an increased association of GluN2B-containing
      NMDA receptors with synaptic scaffolding proteins in aged animals may have
      contributed to the age-related memory declines. 

PMID- 23884938
TI  - Nicotine-modulated subunit stoichiometry affects stability and trafficking of
      alpha3beta4 nicotinic receptor.
AB  - Heteromeric nAChRs are pentameric cation channels, composed of combinations of
      two or three alpha and three or two beta subunits, which play key physiological
      roles in the central and peripheral nervous systems. The prototypical agonist
      nicotine acts intracellularly to upregulate many nAChR subtypes, a phenomenon
      that is thought to contribute to the nicotine dependence of cigarette smokers.
      The alpha3beta4 subtype has recently been genetically linked to nicotine
      dependence and lung cancer; however, the mode of action of nicotine on this
      receptor subtype has been incompletely investigated. Here, using transfected
      mammalian cells as model system, we characterized the response of the human
      alpha3beta4 receptor subtype to nicotine and the mechanism of action of the drug.
      Nicotine, when present at 1 mm concentration, elicited a ~5-fold increase of cell
      surface alpha3beta4 and showed a more modest upregulatory effect also at
      concentrations as low as 10 MUM. Upregulation was obtained if nicotine was
      present during, but not after, pentamer assembly and was caused by increased
      stability and trafficking of receptors assembled in the presence of the drug.
      Experimental determinations as well as computational studies of subunit
      stoichiometry showed that nicotine favors assembly of pentamers with
      (alpha3)2(beta4)3 stoichiometry; these are less prone than (alpha3)3(beta4)2
      receptors to proteasomal degradation and, because of the presence in the beta
      subunit of an endoplasmic reticulum export motif, more efficiently transported to
      the plasma membrane. Our findings uncover a novel mechanism of nicotine-induced
      alpha3beta4 nAChR upregulation that may be relevant also for other nAChR
      subtypes. 

PMID- 23884937
TI  - The role of Drosophila cytidine monophosphate-sialic acid synthetase in the
      nervous system.
AB  - While sialylation plays important functions in the nervous system, the complexity
      of glycosylation pathways and limitations of genetic approaches preclude the
      efficient analysis of these functions in mammalian organisms. Drosophila has
      recently emerged as a promising model for studying neural sialylation. Drosophila
      sialyltransferase, DSiaT, was shown to be involved in the regulation of neural
      transmission. However, the sialylation pathway was not investigated in Drosophila
      beyond the DSiaT-mediated step. Here we focused on the function of Drosophila
      cytidine monophosphate-sialic acid synthetase (CSAS), the enzyme providing a
      sugar donor for DSiaT. Our results revealed that the expression of CSAS is
      tightly regulated and restricted to the CNS throughout development and in adult
      flies. We generated CSAS mutants and analyzed their phenotypes using behavioral
      and physiological approaches. Our experiments demonstrated that mutant phenotypes
      of CSAS are similar to those of DSiaT, including decreased longevity, temperature
      induced paralysis, locomotor abnormalities, and defects of neural transmission at
      neuromuscular junctions. Genetic interactions between CSAS, DSiaT, and voltage
      gated channel genes paralytic and seizure were consistent with the hypothesis
      that CSAS and DSiaT function within the same pathway regulating neural
      excitability. Intriguingly, these interactions also suggested that CSAS and DSiaT
      have some additional, independent functions. Moreover, unlike its mammalian
      counterparts that work in the nucleus, Drosophila CSAS was found to be a
      glycoprotein-bearing N-glycans and predominantly localized in vivo to the Golgi
      compartment. Our work provides the first systematic analysis of in vivo functions
      of a eukaryotic CSAS gene and sheds light on evolutionary relationships among
      metazoan CSAS proteins. 

PMID- 23884939
TI  - Loss of D2 dopamine receptor function modulates cocaine-induced glutamatergic
      synaptic potentiation in the ventral tegmental area.
AB  - Potentiation of glutamate responses is a critical synaptic response to cocaine
      exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which
      cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and
      subsequently AMPA receptors (AMPARs) is not fully understood. In this study we
      demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor
      functional responses via interaction with lysosome-targeting G-protein-associated
      sorting protein1 (GASP1). We also show that the absence of D2 downregulation in
      GASP1-KO mice prevents cocaine-induced potentiation of NMDAR currents, elevation
      of the AMPA/NMDA ratio, and redistribution of NMDAR and AMPAR subunits to the
      membrane. As a pharmacological parallel, coadministration of the high-affinity D2
      agonist, aripiprazole, reduces not only functional downregulation of D2s in
      response to cocaine but also potentiation of NMDAR and AMPAR responses in wild
      type mice. Together these data suggest that functional loss of D2 receptors is a
      critical mechanism mediating cocaine-induced glutamate plasticity in VTA neurons.

PMID- 23884941
TI  - Brain tumor regulates neuromuscular synapse growth and endocytosis in Drosophila
      by suppressing mad expression.
AB  - The precise regulation of synaptic growth is critical for the proper formation
      and plasticity of functional neural circuits. Identification and characterization
      of factors that regulate synaptic growth and function have been under intensive
      investigation. Here we report that brain tumor (brat), which was identified as a
      translational repressor in multiple biological processes, plays a crucial role at
      Drosophila neuromuscular junction (NMJ) synapses. Immunohistochemical analysis
      demonstrated that brat mutants exhibited synaptic overgrowth characterized by
      excess satellite boutons at NMJ terminals, whereas electron microscopy revealed
      increased synaptic vesicle size but reduced density at active zones compared with
      wild-types. Spontaneous miniature excitatory junctional potential amplitudes were
      larger and evoked quantal content was lower at brat mutant NMJs. In agreement
      with the morphological and physiological phenotypes, loss of Brat resulted in
      reduced FM1-43 uptake at the NMJ terminals, indicating that brat regulates
      synaptic endocytosis. Genetic analysis revealed that the actions of Brat at
      synapses are mediated through mothers against decapentaplegic (Mad), the signal
      transduction effector of the bone morphogenetic protein (BMP) signaling pathway.
      Furthermore, biochemical analyses showed upregulated levels of Mad protein but
      normal mRNA levels in the larval brains of brat mutants, suggesting that Brat
      suppresses Mad translation. Consistently, knockdown of brat by RNA interference
      in Drosophila S2 cells also increased Mad protein level. These results together
      reveal an important and previously unidentified role for Brat in synaptic
      development and endocytosis mediated by suppression of BMP signaling. 

PMID- 23884940
TI  - Feedforward inhibition underlies the propagation of cholinergically induced gamma
      oscillations from hippocampal CA3 to CA1.
AB  - Gamma frequency (30-80 Hz) oscillations are implicated in memory processing. Such
      rhythmic activity can be generated intrinsically in the CA3 region of the
      hippocampus from where it can propagate to the CA1 area. To uncover the synaptic
      mechanisms underlying the intrahippocampal spread of gamma oscillations, we
      recorded local field potentials, as well as action potentials and synaptic
      currents in anatomically identified CA1 and CA3 neurons during carbachol-induced
      gamma oscillations in mouse hippocampal slices. The firing of the vast majority
      of CA1 neurons and all CA3 neurons was phase-coupled to the oscillations recorded
      in the stratum pyramidale of the CA1 region. The predominant synaptic input to
      CA1 interneurons was excitatory, and their discharge followed the firing of CA3
      pyramidal cells at a latency indicative of monosynaptic connections. Correlation
      analysis of the input-output characteristics of the neurons and local
      pharmacological block of inhibition both agree with a model in which
      glutamatergic CA3 input controls the firing of CA1 interneurons, with local
      pyramidal cell activity having a minimal role. The firing of phase-coupled CA1
      pyramidal cells was controlled principally by their inhibitory inputs, which
      dominated over excitation. Our results indicate that the synchronous firing of
      CA3 pyramidal cells rhythmically recruits CA1 interneurons and that this
      feedforward inhibition generates the oscillatory activity in CA1. These findings
      identify distinct synaptic mechanisms underlying the generation of gamma
      frequency oscillations in neighboring hippocampal subregions. 

PMID- 23884942
TI  - Survivin Is a transcriptional target of STAT3 critical to estradiol
      neuroprotection in global ischemia.
AB  - Transient global ischemia causes selective, delayed death of hippocampal CA1
      pyramidal neurons in humans and animals. It is well established that estrogens
      ameliorate neuronal death in animal models of focal and global ischemia. However,
      the role of signal transducer and activator of transcription-3 (STAT3) and its
      target genes in estradiol neuroprotection in global ischemia remains unclear.
      Here we show that a single intracerebral injection of 17beta-estradiol to
      ovariectomized female rats immediately after ischemia rescues CA1 neurons
      destined to die. Ischemia promotes activation of STAT3 signaling, association of
      STAT3 with the promoters of target genes, and STAT3-dependent mRNA and protein
      expression of prosurvival proteins in the selectively vulnerable CA1. In animals
      subjected to ischemia, acute postischemic estradiol further enhances activation
      and nuclear translocation of STAT3 and STAT3-dependent transcription of target
      genes. Importantly, we show that STAT3 is critical to estradiol neuroprotection,
      as evidenced by the ability of STAT3 inhibitor peptide and STAT3 shRNA delivered
      directly into the CA1 of living animals to abolish neuroprotection. In addition,
      we identify survivin, a member of the inhibitor-of-apoptosis family of proteins
      and known gene target of STAT3, as essential to estradiol neuroprotection, as
      evidenced by the ability of shRNA to survivin to reverse neuroprotection. These
      findings indicate that ischemia and estradiol act synergistically to promote
      activation of STAT3 and STAT3-dependent transcription of survivin in insulted CA1
      neurons and identify STAT3 and survivin as potentially important therapeutic
      targets in an in vivo model of global ischemia. 

PMID- 23884943
TI  - Error-monitoring and post-error compensations: dissociation between perceptual
      failures and motor errors with and without awareness.
AB  - Whether humans adjust their behavior in response to unaware errors remains a
      controversial issue relevant to insight in neuropsychiatric conditions. Initial
      error awareness studies found that the error-related negativity (ERN), an event
      related potential (ERP) originating in the medial prefrontal cortex after errors,
      activated equally for aware and unaware errors, suggesting a candidate
      preconscious mechanism. However, recent studies demonstrate that the ERN
      decreases after unaware errors. We hypothesized that the ERN is dependent upon
      awareness, and predicted that previous discrepancies might be due to unaware
      errors not being differentiated from perceptually uncertain, low-confidence
      responses that might increase the ERN amplitude. Here we addressed this
      hypothesis by distinguishing between aware errors, unaware errors, and uncertain
      responses, and using stimuli (faces) associated with well established sensory
      ERPs to evaluate the degree of stimulus processing for each trial type. We found
      that while aware and unaware errors were related to failures at the time of
      response, uncertain responses were due to failures at the time of stimulus
      processing indexed by lower amplitude sensory ERPs. Moreover, uncertain responses
      showed similar ERN activity as aware errors, in comparison with decreased
      activity for unaware errors. Finally, compared with aware errors, uncertain
      responses and unaware errors showed reduced neural compensations, such as alpha
      suppression. Together these findings suggest that the ERN is activated by aware
      motor errors as well as sensory failures, and that both awareness and certainty
      are necessary for neural adaptations after errors. 

PMID- 23884944
TI  - Differences in adaptation rates after virtual surgeries provide direct evidence
      for modularity.
AB  - Whether the nervous system relies on modularity to simplify acquisition and
      control of complex motor skills remains controversial. To date, evidence for
      modularity has been indirect, based on statistical regularities in the motor
      commands captured by muscle synergies. Here we provide direct evidence by testing
      the prediction that in a truly modular controller it must be harder to adapt to
      perturbations that are incompatible with the modules. We investigated a reaching
      task in which human subjects used myoelectric control to move a mass in a virtual
      environment. In this environment we could perturb the normal muscle-to-force
      mapping, as in a complex surgical rearrangement of the tendons, by altering the
      mapping between recorded muscle activity and simulated force applied on the mass.
      After identifying muscle synergies, we performed two types of virtual surgeries.
      After compatible virtual surgeries, a full range of movements could still be
      achieved recombining the synergies, whereas after incompatible virtual surgeries,
      new or modified synergies would be required. Adaptation rates after the two types
      of surgery were compared. If synergies were only a parsimonious description of
      the regularities in the muscle patterns generated by a nonmodular controller, we
      would expect adaptation rates to be similar, as both types of surgeries could be
      compensated with similar changes in the muscle patterns. In contrast, as
      predicted by modularity, we found strikingly faster adaptation after compatible
      surgeries than after incompatible ones. These results indicate that muscle
      synergies are key elements of a modular architecture underlying motor control and
      adaptation. 

PMID- 23884945
TI  - Eye-position signals in the dorsal visual system are accurate and precise on
      short timescales.
AB  - Eye-position signals (EPS) are found throughout the primate visual system and are
      thought to provide a mechanism for representing spatial locations in a manner
      that is robust to changes in eye position. It remains unknown, however, whether
      cortical EPS (also known as "gain fields") have the necessary spatial and
      temporal characteristics to fulfill their purported computational roles. To
      quantify these EPS, we combined single-unit recordings in four dorsal visual
      areas of behaving rhesus macaques (lateral intraparietal area, ventral
      intraparietal area, middle temporal area, and the medial superior temporal area)
      with likelihood-based population-decoding techniques. The decoders used knowledge
      of spiking statistics to estimate eye position during fixation from a set of
      observed spike counts across neurons. Importantly, these samples were short in
      duration (100 ms) and from individual trials to mimic the real-time estimation
      problem faced by the brain. The results suggest that cortical EPS provide an
      accurate and precise representation of eye position, albeit with unequal signal
      fidelity across brain areas and a modest underestimation of eye eccentricity. The
      underestimation of eye eccentricity predicted a pattern of mislocalization that
      matches the errors made by human observers. In addition, we found that eccentric
      eye positions were associated with enhanced precision relative to the primary eye
      position. This predicts that positions in visual space should be represented more
      reliably during eccentric gaze than while looking straight ahead. Together, these
      results suggest that cortical eye-position signals provide a useable head
      centered representation of visual space on timescales that are compatible with
      the duration of a typical ocular fixation. 

PMID- 23884947
TI  - How the visual brain encodes and keeps track of time.
AB  - Time is embedded in any sensory experience: the movements of a dance, the rhythm
      of a piece of music, the words of a speaker are all examples of temporally
      structured sensory events. In humans, if and how visual cortices perform temporal
      processing remains unclear. Here we show that both primary visual cortex (V1) and
      extrastriate area V5/MT are causally involved in encoding and keeping time in
      memory and that this involvement is independent from low-level visual processing.
      Most importantly we demonstrate that V1 and V5/MT come into play simultaneously
      and seem to be functionally linked during interval encoding, whereas they operate
      serially (V1 followed by V5/MT) and seem to be independent while maintaining
      temporal information in working memory. These data help to refine our knowledge
      of the functional properties of human visual cortex, highlighting the
      contribution and the temporal dynamics of V1 and V5/MT in the processing of the
      temporal aspects of visual information. 

PMID- 23884946
TI  - Stem cells expanded from the human embryonic hindbrain stably retain regional
      specification and high neurogenic potency.
AB  - Stem cell lines that faithfully maintain the regional identity and developmental
      potency of progenitors in the human brain would create new opportunities in
      developmental neurobiology and provide a resource for generating specialized
      human neurons. However, to date, neural progenitor cultures derived from the
      human brain have either been short-lived or exhibit restricted, predominantly
      glial, differentiation capacity. Pluripotent stem cells are an alternative
      source, but to ascertain definitively the identity and fidelity of cell types
      generated solely in vitro is problematic. Here, we show that hindbrain
      neuroepithelial stem (hbNES) cells can be derived and massively expanded from
      early human embryos (week 5-7, Carnegie stage 15-17). These cell lines are
      propagated in adherent culture in the presence of EGF and FGF2 and retain
      progenitor characteristics, including SOX1 expression, formation of rosette-like
      structures, and high neurogenic capacity. They generate GABAergic, glutamatergic
      and, at lower frequency, serotonergic neurons. Importantly, hbNES cells stably
      maintain hindbrain specification and generate upper rhombic lip derivatives on
      exposure to bone morphogenetic protein (BMP). When grafted into neonatal rat
      brain, they show potential for integration into cerebellar development and
      produce cerebellar granule-like cells, albeit at low frequency. hbNES cells offer
      a new system to study human cerebellar specification and development and to model
      diseases of the hindbrain. They also provide a benchmark for the production of
      similar long-term neuroepithelial-like stem cells (lt-NES) from pluripotent cell
      lines. To our knowledge, hbNES cells are the first demonstration of highly
      expandable neuroepithelial stem cells derived from the human embryo without
      genetic immortalization. 

PMID- 23884948
TI  - Granule cell ascending axon excitatory synapses onto Golgi cells implement a
      potent feedback circuit in the cerebellar granular layer.
AB  - The function of inhibitory interneurons within brain microcircuits depends
      critically on the nature and properties of their excitatory synaptic drive. Golgi
      cells (GoCs) of the cerebellum inhibit cerebellar granule cells (GrCs) and are
      driven both by feedforward mossy fiber (mf) and feedback GrC excitation. Here, we
      have characterized GrC inputs to GoCs in rats and mice. We show that, during
      sustained mf discharge, synapses from local GrCs contribute equivalent charge to
      GoCs as mf synapses, arguing for the importance of the feedback inhibition.
      Previous studies predicted that GrC-GoC synapses occur predominantly between
      parallel fibers (pfs) and apical GoC dendrites in the molecular layer (ML). By
      combining EM and Ca(2+) imaging, we now demonstrate the presence of functional
      synaptic contacts between ascending axons (aa) of GrCs and basolateral dendrites
      of GoCs in the granular layer (GL). Immunohistochemical quantification estimates
      these contacts to be ~400 per GoC. Using Ca(2+) imaging to identify synaptic
      inputs, we show that EPSCs from aa and mf contacts in basolateral dendrites
      display similarly fast kinetics, whereas pf inputs in the ML exhibit markedly
      slower kinetics as they undergo strong filtering by apical dendrites. We estimate
      that approximately half of the local GrC contacts generate fast EPSCs, indicating
      their basolateral location in the GL. We conclude that GrCs, through their aa
      contacts onto proximal GoC dendrites, define a powerful feedback inhibitory
      circuit in the GL. 

PMID- 23884949
TI  - TrkB.T1 contributes to neuropathic pain after spinal cord injury through
      regulation of cell cycle pathways.
AB  - Spinal cord injury (SCI) frequently causes severe, persistent central neuropathic
      pain that responds poorly to conventional pain treatments. Brain-derived
      neurotrophic factor (BDNF) signaling appears to contribute to central
      sensitization and nocifensive behaviors in certain animal models of chronic pain
      through effects mediated in part by the alternatively spliced truncated isoform
      of the BDNF receptor tropomyosin-related kinase B.T1 (trkB.T1). Mechanisms
      linking trkB.T1 to SCI-induced chronic central pain are unknown. Here, we
      examined the role of trkB.T1 in central neuropathic pain after spinal cord
      contusion. Genetic deletion of trkB.T1 in mice significantly reduced post-SCI
      mechanical hyperesthesia, locomotor dysfunction, lesion volumes, and white matter
      loss. Whole genome analysis, confirmed at the protein level, revealed that cell
      cycle genes were upregulated in trkB.T1(+/+) but not trkB.T1(-/-) spinal cord
      after SCI. TGFbeta-induced reactive astrocytes from WT mice showed increased cell
      cycle protein expression that was significantly reduced in astrocytes from
      trkB.T1(-/-) mice that express neither full-length trkB nor trkB.T1.
      Administration of CR8, which selectively inhibits cyclin-dependent kinases,
      reduced hyperesthesia, locomotor deficits, and dorsal horn (SDH) glial changes
      after SCI, similar to trkB.T1 deletion, without altering trkB.T1 protein
      expression. In trkB.T1(-/-) mice, CR8 had no effect. These data indicate that
      trkB.T1 contributes to the pathobiology of SCI and SCI pain through modulation of
      cell cycle pathways and suggest new therapeutic targets. 

PMID- 23884951
TI  - Anodal transcranial direct current stimulation temporarily reverses age
      associated cognitive decline and functional brain activity changes.
AB  - The rising proportion of elderly people worldwide will yield an increased
      incidence of age-associated cognitive impairments, imposing major burdens on
      societies. Consequently, growing interest emerged to evaluate new strategies to
      delay or counteract cognitive decline in aging. Here, we assessed immediate
      effects of anodal transcranial direct current stimulation (atDCS) on cognition
      and previously described detrimental changes in brain activity attributable to
      aging. Twenty healthy elderly adults were assessed in a crossover sham-controlled
      design using functional magnetic resonance imaging (fMRI) and concurrent
      transcranial DCS administered to the left inferior frontal gyrus. Effects on
      performance and task-related brain activity were evaluated during overt semantic
      word generation, a task that is negatively affected by advanced age. Task-absent
      resting-state fMRI (RS-fMRI) assessed atDCS-induced changes at the network level
      independent of performance. Twenty matched younger adults served as controls.
      During sham stimulation, task-related fMRI demonstrated that enhanced bilateral
      prefrontal activity in older adults was associated with reduced performance. RS
      fMRI revealed enhanced anterior and reduced posterior functional brain
      connectivity. atDCS significantly improved performance in older adults up to the
      level of younger controls; significantly reduced task-related hyperactivity in
      bilateral prefrontal cortices, the anterior cingulate gyrus, and the precuneus;
      and induced a more "youth-like" connectivity pattern during RS-fMRI. Our results
      provide converging evidence from behavioral analysis and two independent
      functional imaging paradigms that a single session of atDCS can temporarily
      reverse nonbeneficial effects of aging on cognition and brain activity and
      connectivity. These findings may translate into novel treatments to ameliorate
      cognitive decline in normal aging in the future. 

PMID- 23884950
TI  - D-serine in glia and neurons derives from 3-phosphoglycerate dehydrogenase.
AB  - d-Serine is an endogenous ligand for NMDARs generated from l-serine by the enzyme
      serine racemase (Srr). Both neuronal and glial localizations have been reported
      for d-serine and Srr. 3-Phosphoglycerate dehydrogenase is an exclusively
      astrocytic enzyme that catalyzes the first committed step of l-serine
      biosynthesis. Using transgenic mice expressing enhanced green fluorescent protein
      under the Srr promoter and mice with targeted deletion of Srr or 3
      Phosphoglycerate dehydrogenase, we demonstrate predominantly neuronal sources of
      d-serine dependent on astrocytic supply of l-serine. These findings clarify the
      cellular basis for the regulation of NMDAR neurotransmission by d-serine. 

PMID- 23884952
TI  - Visually evoked responses in extrastriate area MT after lesions of striate cortex
      in early life.
AB  - Lesions of striate cortex [primary visual cortex (V1)] in adult primates result
      in blindness. In contrast, V1 lesions in neonates typically allow much greater
      preservation of vision, including, in many human patients, conscious perception.
      It is presently unknown how this marked functional difference is related to
      physiological changes in cortical areas that are spared by the lesions. Here we
      report a study of the middle temporal area (MT) of adult marmoset monkeys that
      received unilateral V1 lesions within 6 weeks of birth. In contrast with
      observations after similar lesions in adult monkeys, we found that virtually all
      neurons in the region of MT that was deprived of V1 inputs showed robust
      responses to visual stimulation. These responses were very similar to those
      recorded in neurons with receptive fields outside the lesion projection zones in
      terms of firing rate, signal-to-noise ratio, and latency. In addition, the normal
      retinotopic organization of MT was maintained. Nonetheless, we found evidence of
      a very specific functional deficit: direction selectivity, a key physiological
      characteristic of MT that is known to be preserved in many cells after adult V1
      lesions, was absent. These results demonstrate that lesion-induced reorganization
      of afferent pathways is sufficient to develop robust visual function in primate
      extrastriate cortex, highlighting a likely mechanism for the sparing of vision
      after neonatal V1 lesions. However, they also suggest that interactions with V1
      in early postnatal life are critical for establishing stimulus selectivity in MT.

PMID- 23884953
TI  - Ten-m2 is required for the generation of binocular visual circuits.
AB  - Functional binocular vision requires that inputs arising from the two retinae are
      integrated and precisely organized within central visual areas. Previous studies
      have demonstrated an important role for one member of the Ten-m/Odz/teneurin
      family, Ten-m3, in the mapping of ipsilateral retinal projections. Here, we have
      identified a distinct role for another closely related family member, Ten-m2, in
      the formation of the ipsilateral projection in the mouse visual system. Ten-m2
      expression was observed in the retina, dorsal lateral geniculate nucleus (dLGN),
      superior colliculus (SC), and primary visual cortex (V1) of the developing mouse.
      Anterograde and retrograde tracing experiments in Ten-m2 knock-out (KO) mice
      revealed a specific decrease in ipsilateral retinal ganglion cells projecting to
      dLGN and SC. This reduction was most prominent in regions corresponding to
      ventral retina. No change in the topography of ipsilateral or contralateral
      projections was observed. While expression of a critical ipsilateral fate
      determinant, Zic2, appeared unaltered, a notable reduction in one of its
      downstream targets, EphB1, was observed in ventral retina, suggesting that Ten-m2
      may interact with this molecular pathway. Immunohistochemistry for c-fos, a
      neural activity marker, revealed that the area of V1 driven by ipsilateral inputs
      was reduced in KOs, while the ratio of ipsilateral-to-contralateral responses
      contributing to binocular activation during visually evoked potential recordings
      was also diminished. Finally, a novel two-alternative swim task revealed specific
      deficits associated with dorsal visual field. These data demonstrate a
      requirement for Ten-m2 in the establishment of ipsilateral projections, and thus
      the generation of binocular circuits, critical for mammalian visual function. 

PMID- 23884954
TI  - Essential role for synaptopodin in dendritic spine plasticity of the developing
      hippocampus.
AB  - Dendritic spines are a major substrate of brain plasticity. Although many studies
      have focused on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-mediated
      regulation of spine dynamics and synaptic function in adult brain, much less is
      know about protein kinase A (PKA)-dependent regulation of spine shape dynamics
      during postnatal brain development. Synaptopodin is a dendritic spine associated
      modulator of actin dynamics and a substrate of PKA. Here we show that NMDA and
      cAMP-induced dendritic spine expansion is impaired in hippocampal slices from 15-
      and 21-d-old synaptopodin-deficient mice. We further show that synaptopodin is
      required for full expression of PKA-dependent hippocampal long-term potentiation
      in 15- and 21-d-old, but not adult, mice. PKA-induced cAMP response element
      binding phosphorylation is normal in the hippocampus of synaptopodin-deficient
      mice, suggesting that synaptopodin functions independently of cAMP response
      element-binding. Our results identify synaptopodin as a substrate of PKA in
      hippocampal neurons and point to an essential role for synaptopodin in activity
      dependent regulation of dendritic spine dynamics and synaptic plasticity in
      postnatal brain development. 

PMID- 23884955
TI  - Neural correlates of the divergence of instrumental probability distributions.
AB  - Flexible action selection requires knowledge about how alternative actions impact
      the environment: a "cognitive map" of instrumental contingencies. Reinforcement
      learning theories formalize this map as a set of stochastic relationships between
      actions and states, such that for any given action considered in a current state,
      a probability distribution is specified over possible outcome states. Here, we
      show that activity in the human inferior parietal lobule correlates with the
      divergence of such outcome distributions-a measure that reflects whether
      discrimination between alternative actions increases the controllability of the
      future-and, further, that this effect is dissociable from those of other
      information theoretic and motivational variables, such as outcome entropy, action
      values, and outcome utilities. Our results suggest that, although ultimately
      combined with reward estimates to generate action values, outcome probability
      distributions associated with alternative actions may be contrasted independently
      of valence computations, to narrow the scope of the action selection problem. 

PMID- 23884956
TI  - Transgenic overexpression of Sox17 promotes oligodendrocyte development and
      attenuates demyelination.
AB  - We have previously demonstrated that Sox17 regulates cell cycle exit and
      differentiation in oligodendrocyte progenitor cells. Here we investigated its
      function in white matter (WM) development and adult injury with a newly generated
      transgenic mouse overexpressing Sox17 in the oligodendrocyte lineage under the
      CNPase promoter. Sox17 overexpression in CNP-Sox17 mice sequentially promoted
      postnatal oligodendrogenesis, increasing NG2 progenitor cells from postnatal day
      (P) 15, then O4+ and CC1+ cells at P30 and P120, respectively. Total Olig2+
      oligodendrocyte lineage cells first decreased between P8 and P22 through Sox17
      mediated increase in apoptotic cell death, and thereafter significantly exceeded
      WT levels from P30 when cell death had ceased. CNP-Sox17 mice showed increased
      Gli2 protein levels and Gli2+ cells in WM, indicating that Sox17 promotes the
      generation of oligodendrocyte lineage cells through Hedgehog signaling. Sox17
      overexpression prevented cell loss after lysolecithin-induced demyelination by
      increasing Olig2+ and CC1+ cells in response to injury. Furthermore, Sox17
      overexpression abolished the injury-induced increase in TCF7L2/TCF4+ cells, and
      protected oligodendrocytes from apoptosis by preventing decreases in Gli2 and Bcl
      2 expression that were observed in WT lesions. Our study thus reveals a biphasic
      effect of Sox17 overexpression on cell survival and oligodendrocyte formation in
      the developing WM, and that its potentiation of oligodendrocyte survival in the
      adult confers resistance to injury and myelin loss. This study demonstrates that
      overexpression of this transcription factor might be a viable protective strategy
      to mitigate the consequences of demyelination in the adult WM. 

PMID- 23884959
TI  - Hypoxia enhances the expression of prostate-specific antigen by modifying the
      quantity and catalytic activity of Jumonji C domain-containing histone
      demethylases.
AB  - Oxygen concentration in prostate cancer tissue is significantly low, i.e. ~0.3%
      O2. This study showed that pathological hypoxia (<0.5% O2) increased the
      expression of androgen receptor (AR) target genes such as prostate-specific
      antigen (PSA) and kallikrein-related peptidase 2 in LNCaP human prostate cancer
      cells by modifying the quantity and activity of related Jumonji C domain
      containing histone demethylases (JMJDs). Under pathological hypoxia, the
      catalytic activities of JMJD2A, JMJD2C and Jumonji/ARID domain-containing protein
      1B (JARID1B) were blocked due to the lack of their substrate, i.e. oxygen.
      Chromatin immunoprecipitation analyses showed that hypoxia increased the
      appearance of H3K9me3 and H3K4me3, substrates of JMJD2s and JARID1B,
      respectively, in the PSA enhancer. In contrast, JMJD1A, which demethylates both
      H3K9me2 and H3K9me1, maintained its catalytic activity even under severe hypoxia.
      Furthermore, hypoxia increased the expression of JMJD1A. Hypoxia and androgen
      additively increased the recruitment of JMJD1A and p300 on the enhancer region of
      PSA through interaction with the hypoxia-inducible factor-1alpha and AR, both of
      which bind the PSA enhancer. Thus, hypoxia enhanced the demethylation of H3K9me2
      and H3K9me1, leading to provide unmethylated H3K9 residues that are substrates
      for histone acetyltransferase, p300. Consequently, hypoxia increased the
      acetylation of histones of the PSA enhancer, which facilitates its transcription.

PMID- 23884961
TI  - A review of the concepts, terminologies and dilemmas in the assessment of
      decisional capacity: a focus on alcoholism.
AB  - OBJECTIVE: The formal assessment of a person's capacity for making reasoned
      decisions is an infrequent and usually unappealing clinical task. The purpose of
      this paper is to dissect the task, consider the component parts, clarify those
      aspects that can be problematic and highlight those that remain so. METHOD: The
      paper reviews the concepts, terminologies and dilemmas around alcoholism,
      insight, lack of insight, denial, judgement, will, decisional capacity and
      competence. CONCLUSION: Assessments of patients suffering from alcoholism (or any
      other dyscontrol problem such as deliberate self-harm, problem gambling or eating
      disorders) are likely to evoke unease because of the interweaving of potentially
      disputable phenomenological, clinical, ethical, semantic and legal aspects.
      Familiarity with the concepts and terms around decisional capacity helps to
      orientate clinicians in their work. There remain some particular conceptual
      issues that are in need of further scholarly attention.

PMID- 23884957
TI  - Artemin, a glial cell line-derived neurotrophic factor family member, induces
      TRPM8-dependent cold pain.
AB  - Chronic pain associated with injury or disease can result from dysfunction of
      sensory afferents whereby the threshold for activation of pain-sensing neurons
      (nociceptors) is lowered. Neurotrophic factors control nociceptor development and
      survival, but also induce sensitization through activation of their cognate
      receptors, attributable, in part, to the modulation of ion channel function.
      Thermal pain is mediated by channels of the transient receptor potential (TRP)
      family, including the cold and menthol receptor TRPM8. Although it has been shown
      that TRPM8 is involved in cold hypersensitivity, the molecular mechanisms
      underlying this pain modality are unknown. Using microarray analyses to identify
      mouse genes enriched in TRPM8 neurons, we found that the glial cell line-derived
      neurotrophic factor (GDNF) family receptor GFRalpha3 is expressed in a
      subpopulation of TRPM8 sensory neurons that have the neurochemical profile of
      cold nociceptors. Moreover, we found that artemin, the specific GFRalpha3 ligand
      that evokes heat hyperalgesia, robustly sensitized cold responses in a TRPM8
      dependent manner in mice. In contrast, GFRalpha1 and GFRalpha2 are not
      coexpressed with TRPM8 and their respective ligands GDNF and neurturin did not
      induce cold pain, whereas they did evoke heat hyperalgesia. Nerve growth factor
      induced mild cold sensitization, consistent with TrkA expression in TRPM8
      neurons. However, bradykinin failed to alter cold sensitivity even though its
      receptor expresses in a subset of TRPM8 neurons. These results show for the first
      time that only select neurotrophic factors induce cold sensitization through
      TRPM8 in vivo, unlike the broad range of proalgesic agents capable of promoting
      heat hyperalgesia. 

PMID- 23884962
TI  - Indigenous men's groups and social and emotional well-being: an indigenous
      doctor's perspective.
AB  - OBJECTIVES: Traditional indigenous society promoted the social and emotional well
      being of indigenous men through the meeting of men in daily life and during
      ceremonial times. There is an increasing recognition that men's groups use
      similar mechanisms to enhance the social and emotional well-being of participants
      and their communities. This paper seeks to increase understanding of the
      processes and impacts of contemporary indigenous men's groups from an indigenous
      doctor's perspective. METHOD: Review of published and unpublished literature and
      reflections on the primary author's experiences within several indigenous men's
      groups using a participatory action research model were used to examine how
      participation within these groups can improve social and emotional well-being.
      RESULTS: There is a scarcity of published data on the distribution, activities
      and outcomes of indigenous men's groups. Published qualitative and experiential
      observations suggest that they contribute to improved social and emotional well
      being for participants, their families and communities. CONCLUSIONS: Men's groups
      may be a good adjunct to the outpatient care of indigenous patients. As the
      published literature is entirely qualitative, mixed methods evaluation using
      appropriate and sensitive measures would assist in systematically capturing the
      impacts and outcomes of men's groups. Such evaluations could enhance programme
      longevity and encourage the referral of patients by mainstream mental health
      practitioners.

PMID- 23884963
TI  - Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for
      assisted reproduction.
AB  - BACKGROUND: Subfertility is a condition found in up to 15% of couples of
      reproductive age. Gamete micromanipulation, such as intracytoplasmic sperm
      injection (ICSI), is very useful for treating couples with compromised sperm
      parameters. Recently a new method of sperm selection named 'motile sperm
      organelle morphology examination' (MSOME) has been described and the spermatozoa
      selected under high magnification (over 6000x) used for ICSI. This new technique,
      named intracytoplasmic morphologically selected sperm injection (IMSI), has a
      theoretical potential to improve reproductive outcomes among couples undergoing
      assisted reproduction techniques (ART). OBJECTIVES: To compare the effectiveness
      and safety of IMSI and ICSI in couples undergoing ART. SEARCH METHODS: We
      searched for randomised controlled trials (RCT) in electronic databases (Cochrane
      Menstrual Disorders and Subfertility Group Specialized Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO,
      CINAHL, LILACS), trials registers (ClinicalTrials.gov, Current Controlled Trials,
      World Health Organization International Clinical Trials Registry Platform),
      conference abstracts (ISI Web of knowledge), and grey literature (OpenGrey); in
      addition, we handsearched the reference lists of included studies and similar
      reviews. We performed the last electronic search on 8 May 2013. SELECTION
      CRITERIA: We considered only truly randomised controlled trials comparing ICSI
      and IMSI to be eligible; we did not include quasi or pseudo-randomised trials. We
      included studies that permitted the inclusion of the same participant more than
      once (cross-over or 'per cycle' trials) only if data regarding the first
      treatment of each participant were available. DATA COLLECTION AND ANALYSIS: Two
      review authors independently performed study selection, data extraction, and
      assessment of the risk of bias and we solved disagreements by consulting a third
      review author. We corresponded with study investigators in order to resolve any
      queries, as required. MAIN RESULTS: The search retrieved 294 records; from those,
      nine parallel design studies were included, comprising 2014 couples (IMSI = 1002;
      ICSI = 1012). Live birth was evaluated by only one trial and there was no
      significant evidence of a difference between IMSI and ICSI (risk ratio (RR) 1.14,
      95% confidence interval (CI) 0.79 to 1.64, 1 RCT, 168 women, I(2) = not
      applicable, low-quality evidence). IMSI was associated with a significant
      improvement in clinical pregnancy rate (RR 1.29, 95% CI 1.07 to 1.56, 9 RCTs,
      2014 women, I(2) = 57%, very-low-quality evidence). We downgraded the quality of
      this evidence because of imprecision, inconsistency, and strong indication of
      publication bias. We found no significant difference in miscarriage rate between
      IMSI and ICSI (RR 0.82, 95% CI 0.59 to 1.14, 6 RCTs, 552 clinical pregnancies,
      I(2) = 17%, very-low-quality evidence). None of the included studies reported
      congenital abnormalities. AUTHORS' CONCLUSIONS: Results from RCTs do not support
      the clinical use of IMSI. There is no evidence of effect on live birth or
      miscarriage and the evidence that IMSI improves clinical pregnancy is of very low
      quality. There is no indication that IMSI increases congenital abnormalities.
      Further trials are necessary to improve the evidence quality before recommending
      IMSI in clinical practice.

PMID- 23884964
TI  - CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the
      hypothalamus.
AB  - AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy
      homeostasis, can be influenced by several hormones. Tissue-specific alteration of
      AMPK activity by glucocorticoids may explain the increase in appetite, the
      accumulation of lipids in adipose tissues, and the detrimental cardiac effects of
      Cushing's syndrome. Endocannabinoids are known to mediate the effects of various
      hormones and to influence AMPK activity. Cannabinoids have central orexigenic and
      direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In
      our preliminary experiments, WT mice received implants of a corticosterone
      containing pellet to establish a mouse model of Cushing's syndrome. Subsequently,
      WT and Cb1 (Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone
      and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac
      tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight
      gain and of increase in hypothalamic and hepatic AMPK activity. In adipose
      tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid
      induced drop was observed, similar to that observed in WT mice. Cardiac AMPK
      levels were reduced in CB1-KO mice, but while WT mice showed significantly
      reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a
      paradoxical increase. Our findings indicate the importance of the CB1 receptor in
      the central orexigenic effect of glucocorticoid-induced activation of
      hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur
      independently of the CB1 receptor, but the receptor appears to alter the
      responsiveness of the liver and myocardial tissues to glucocorticoids. In
      conclusion, our data suggest that an intact cannabinoid pathway is required for
      the full metabolic effects of chronic glucocorticoid excess. 

PMID- 23884965
TI  - Automatic assessment of stent neointimal coverage by intravascular optical
      coherence tomography.
AB  - AIMS: This study aimed to validate automatic intravascular optical coherence
      tomography (IVOCT) analysis for the evaluation of neointimal coverage in response
      to stent implantation. METHODS AND RESULTS: Fourteen stented segments in common
      iliac arteries, acquired from a total of seven adult male New Zealand White
      rabbits, were interrogated in vivo by IVOCT. Durable polymer everolimus-eluting
      stents (EES; Xience V, Abbott Vascular, Santa Clara, CA, USA) were used
      exclusively. Comparison with histology was made in a total of 63 pairs of images,
      where neointimal thickness over corresponding individual stent struts was
      assessed. A high correlation coefficient (R = 0.85, P < 0.001) was obtained by
      comparing automatic IVOCT analysis with histology. Moreover, Bland-Altman
      statistics showed good limits of agreement (LOAs) of +/-45 um, with an average
      difference of -10 um. In addition, manual IVOCT assessment presented very similar
      results when compared with histology (R = 0.83, P < 0.001 and LOA = +/-48 um with
      an average difference of -8 um). Therefore, a very high correlation value was
      found, comparing manual to automatic IVOCT measurements (R = 0.95, P < 0.001)
      together with good LOAs (+/-27 um) and an average difference of -2 um.
      CONCLUSION: The results of the study suggest that automatic IVOCT analysis is a
      reliable and accurate tool able to speed up current IVOCT analysis procedures.
      This would potentially allow for a better integration of IVOCT in clinical
      practice and clinical studies assessing vascular response to stent implantation
      in a large series of patients.

PMID- 23884966
TI  - Bioabsorbable scaffold optimization in provisional stenting: insight from optical
      coherence tomography.

PMID- 23884968
TI  - Breast-feeding initiation in women with pregestational diabetes mellitus.
AB  - OBJECTIVE: To examine feeding practices and factors associated with breast
      feeding initiation (BFI) in women with pregestational diabetes mellitus (PGDM)
      and their infants. METHODS: In all, 392 PGDM (135 late preterm and 257 term)
      pregnancies were studied. Infant feeding preference was ascertained on admission.
      RESULTS: After birth, 166 (42%) of the infants received well-baby care, whereas
      226 (58%) were admitted to the newborn intensive care unit (NICU). Hypoglycemia
      (blood glucose <40 mg/dL), which occurred in 128 (33%) of all infants, did not
      influence BFI. Of 257 women who intended to BF, 55% initiated BF. Also, 5% of 105
      women who intended to feed formula and 13% of the 30 undecided later initiated
      BF. CONCLUSIONS: The BFI rate for women with PGDM is remarkably low even among
      those who intended to BF. Factors associated with BFI failure in this population
      were primiparity, African American race, lower education, smoking, lack of
      intention to BF, and NICU admission.

PMID- 23884967
TI  - Persistently obese youth: interactions between parenting styles and feeding
      practices with child temperament.
AB  - OBJECTIVE: To assess the interaction of parent and child characteristics with
      feeding practices and mealtime functioning. DESIGN: Longitudinal, predictive
      study comparing baseline characteristics with follow-up assessments.
      PARTICIPANTS: The caregivers of 52 persistently obese youth and 32 nonoverweight
      comparison youth completed measurements of child temperament, parental feeding
      practices, parenting styles, and interactions during mealtimes. RESULTS:
      Adolescents with persistent obesity were significantly more likely to be parented
      using problematic feeding practices when parents also reported difficult child
      temperaments. Additionally, adolescents with persistent obesity and difficult
      temperaments were significantly more likely to have lower levels of positive
      mealtime interactions. CONCLUSION: Persistently obese youth are at increased risk
      for problematic parental feeding practices and mealtime functioning, particularly
      when youth are described as having difficult temperaments. These results indicate
      that further investigations are needed to better understand the mechanisms
      linking parent and child characteristics with health-related behaviors for
      adolescents with obesity.

PMID- 23884969
TI  - Diagnosis and management of varicose veins in the legs: summary of NICE guidance.

PMID- 23884970
TI  - Bad medicine: motherhood.

PMID- 23884971
TI  - Patient safety without the blame game.

PMID- 23884972
TI  - How to learn scepticism.

PMID- 23884973
TI  - The birth and death of the Liverpool care pathway.

PMID- 23884974
TI  - What does oseltamivir do, and how will we know?

PMID- 23884975
TI  - WHO survey finds half of countries do not have clinical guidelines for treating
      hepatitis.

PMID- 23884976
TI  - Reliance of 111 on non-clinical staff has increased pressure on emergency
      departments, MPs say.

PMID- 23884977
TI  - An unusual nasopharyngeal foreign body with unusual presentation as nasal
      regurgitation and change in voice.
AB  - Upper aerodigestive tract may harbour foreign bodies such as sponges, grains, toy
      parts, stones, paper, insects, cotton, etc. These objects may go undetected for
      days or even weeks. A metallic foreign body after being inhaled and ultimately
      being lodged in the nasopharynx is a rare entity. We report a case of an unusual
      nasopharyngeal foreign body (metallic bolt) presenting with symptoms of nasal
      regurgitation and change in voice in a 2-year boy. The foreign body was diagnosed
      by X-ray skull lateral view including nasopharynx and was removed under general
      anaesthesia. 

PMID- 23884978
TI  - Adrenal inflammatory myofibroblastic tumour.
AB  - A rare case of large adrenal mass which was non-functioning is presented. It is
      difficult to make preoperative diagnosis in these cases as the imaging findings
      are non-specific. Radical excision is mandatory as preoperative malignancy cannot
      be ruled out. 

PMID- 23884979
TI  - Bilateral macrostomia.
AB  - Macrostomia as a rare facial deformity is classified among facial clefts. It is a
      rare congenital anomaly which affects the aesthetics and function of the oral
      cavity. It is usually associated with deformities of other structures developed
      from the first and second branchial arches. Bilateral transverse cleft occurring
      alone is uncommon. Here we report a case of bilateral macrostomia (bilateral lip
      cleft) in a 5-year-old girl as a sole entity without other skeletal and facial
      deformities. 

PMID- 23884980
TI  - Trends in cardiovascular diseases and cancer mortality in 45 countries from five
      continents (1980-2010).
AB  - BACKGROUND: Cardiovascular diseases (CVD) and cancer are worldwide main causes of
      death with mortality trends varying across countries with different levels of
      economic development. DESIGN AND METHODS: We analysed trends in CVD and cancer
      mortality for 37 European countries, five high-income non-European countries and
      four leading emerging economies (BRICS) using data from the World Health
      Organization database for the period 1980-2010. RESULTS: In high-income
      countries, CVD mortality trends are characterized by steep declines over the last
      decades, while a downward trend in cancer mortality started more recently and was
      less pronounced. This resulted in the gradual convergence of the CVD and cancer
      mortality rates, and the latter are already higher in some countries. The
      absolute number of CVD deaths decreased in most settings, while cancer deaths
      increased in nearly all countries. Among the BRICS, China and South Africa share
      a similar pattern of no meaningful variation in both CVD and cancer age
      standardized mortality rates and an increase in the overall number of deaths by
      these causes. Brazil presents trends similar to those of high-income countries,
      except for the still increasing number of CVD deaths. CONCLUSIONS: The
      substantial decreases in CVD mortality over the last decades have overcome the
      impact of the growth and ageing of populations in the overall number of deaths,
      while stabilization in the number of cancer deaths was observed only in some of
      the high-income countries.

PMID- 23884981
TI  - Translating guidelines to practice: findings from a multidisciplinary preventive
      cardiology programme in the west of Ireland.
AB  - AIMS: The aim of this observational, descriptive study is to evaluate the impact
      of an intensive, evidence-based preventive cardiology programme on medical and
      lifestyle risk factors in patients at high risk of developing cardiovascular
      disease (CVD). METHODS: Increased CVD risk patients and their family
      members/partners were invited to attend a 16-week programme consisting of a
      professional multidisciplinary lifestyle intervention, with appropriate risk
      factor and therapeutic management in a community setting. Smoking, dietary
      habits, physical activity levels, waist circumference and body mass index, and
      medical risk factors were measured at initial assessment, at end of programme,
      and at 1-year follow up. RESULTS: Adherence to the programme was high, with 375
      (87.2%) participants and 181 (84.6%) partners having completed the programme,
      with 1-year data being obtained from 235 (93.6%) patients and 107 (90.7%)
      partners. There were statistically significant improvements in both lifestyle
      (body mass index, waist circumference, physical activity, Mediterranean diet
      score, fish, fruit, and vegetable consumption, smoking cessation rates),
      psychosocial (anxiety and depression scales and quality of life indices), and
      medical risk factors (blood pressure, lipid and glycaemic targets) between
      baseline and end of programme, with these improvements being sustained at 1-year
      follow up. CONCLUSIONS: These findings demonstrate how a holistic model of CVD
      prevention can improve cardiovascular risk factors by achieving healthier
      lifestyles and optimal medical management.

PMID- 23884982
TI  - Dacryoadenitis as first presenting feature in systemic lupus erythematosus.

PMID- 23884983
TI  - Transcatheter aortic valve replacement for advanced valvular disease in active
      SLE and APS.
AB  - Valvular heart disease is a relatively common finding in systemic lupus
      erythematosus (SLE) and antiphospholipid syndrome (APS), sometimes necessitating
      valve surgery. Valve replacement may result in significant early and late
      morbidity and mortality. Surgical risks are even greater when co-morbid
      conditions including active SLE and renal involvement are present. This is the
      first report of the successful use of transcatheter aortic valve replacement
      (TAVR) for severe critical aortic stenosis in a patient with active SLE, renal
      failure and APS. TAVR may represent an additional, safer, approach to cardiac
      valve replacement in appropriately selected patients particularly where surgical
      risk is high and active disease present.

PMID- 23884984
TI  - Chromosomally integrated human herpesvirus 6 in a patient with systemic lupus
      erythematosus.

PMID- 23884985
TI  - Glucocorticoid downregulates expression of IL-12 family cytokines in systemic
      lupus erythematosus patients.
AB  - OBJECTIVE: This study aims to investigate expression of interleukin 12 (IL-12)
      family cytokines IL-12, IL-23, IL-27 and IL-35 in systemic lupus erythematosus
      (SLE) patients and the effect of glucocorticoid (GC) treatment on their
      expression. METHODS: Plasma concentration of IL-12, IL-23, IL-27, IL-35, IL-6 and
      anti-double-stranded DNA (dsDNA) antibodies in 30 newly diagnosed severe SLE
      patients and 30 matched healthy subjects was measured by enzyme-linked
      immunosorbent assay. The correlation between the levels of IL-12 family cytokines
      and the levels of IL-6 or anti-dsDNA antibodies was analyzed by Spearman rank
      correlation. RESULTS: Significantly higher levels of plasma IL-12, IL-23, IL-27,
      IL-35, IL-6 and anti-dsDNA antibodies were observed in SLE patients compared with
      healthy controls (p < 0.05), and after prednisone treatment, the serum levels of
      IL-12 family cytokines decreased significantly. Moreover, serum levels of IL-12,
      IL-23, IL-27 and IL-35 were correlated with serum levels of IL-6 and anti-dsDNA
      antibodies in pre-treatment as well as post-treatment SLE patients. CONCLUSIONS:
      SLE patients have increased plasma levels of IL-12 family cytokines and GCs can
      downregulate the expression of them in SLE patients. Therefore, members of the IL
      12 family may be involved in the pathophysiological process of SLE.

PMID- 23884986
TI  - SLE disease per se contributes to deterioration in bone mineral density,
      microstructure and bone strength.
AB  - OBJECTIVE: The objective of this report is to assess the effect of systemic lupus
      erythematosus (SLE) disease itself on deterioration of bone mineral density
      (BMD), microstructure and bone strength. METHOD: Thirty age-matched SLE patients
      on long-term glucocorticoids (GC) (SLE/GC), 30 SLE patients without GC (SLE/non
      GC) and 60 healthy controls were examined. Areal BMD (aBMD) was measured by dual
      energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), and
      architectural parameters at the nondominant distal radius were assessed by high
      resolution peripheral quantitative computed tomography (HR-pQCT). Bone strength
      was estimated by HR-pQCT-based micro-finite element analysis. RESULTS: Adjusted
      for menopausal status and adjusted calcium level, when compared with controls,
      SLE/non-GC patients had significantly lower aBMD at femoral neck and total hip,
      and diminished radial total vBMD, cortical area, vBMD and thickness,
      respectively, by 8.3%, 8%, 2.7% and 9.2%, as well as significant compromised bone
      strength (stiffness, failure load and apparent modulus) by 8.3%, 9.1% and 9.5%,
      respectively. Similar alterations were also found in SLE/GC patients when
      compared to controls. In the premenopausal subgroup analysis, when compared with
      controls, total hip aBMD and radial cortical area were significantly lower in
      SLE/non-GC patients, and cortical area and thickness were significantly deficit
      in SLE/GC patients. However, no significant difference in any bone variables was
      present between SLE/GC and SLE/non-GC patients in the entire cohort or in the
      premenopausal subgroup. CONCLUSION: SLE disease per se contributes to the
      deterioration in bone density, cortical microstructure and bone strength. This
      might help to explain the considerably higher fracture risk seen in SLE patients.

PMID- 23884987
TI  - Multiple autoimmune syndrome revealed by nephrogenic diabetes insipidus and
      hypokalaemic paralysis.
AB  - A presentation of postpartum polydipsia and polyuria followed by periodic
      weakness led to the diagnosis of nephrogenic diabetes insipidus and hypokalaemic
      paralysis, both of which are complications of primary Sjogren's syndrome (pSS).
      The clinically dominant pSS was taken to coexist with long-latent systemic lupus
      erythematosus and asymptomatic autoimmune thyroid disease. This case of multiple
      autoimmune syndrome is a distinctive subgroup of autoimmune disorders that is
      increasingly recognized. Female hormone levels appeared to play a role in disease
      pathogenesis in this case. The patient was predicted to have a favourable
      prognosis due to the absence of major organ involvement. This case revealed an
      uncommon form of complex polyautoimmune phenomena and should prompt physicians to
      extend immunological screening, particularly for females with multiple illnesses.

PMID- 23884988
TI  - Physicochemical and immunological studies on mitochondrial DNA modified by
      peroxynitrite: implications of neo-epitopes of mitochondrial DNA in the
      etiopathogenesis of systemic lupus erythematosus.
AB  - BACKGROUND AND OBJECTIVE: Recent evidence has demonstrated that mitochondria
      possess their own nitric oxide synthase (mtNOS) and can produce endogenous
      reactive-nitrogen-species (RNS) including peroxynitrite (ONOO(-)). This study was
      undertaken to investigate the role of mitochondrial DNA (mtDNA) damage by ONOO(-)
      in systemic lupus erythematosus (SLE) autoimmunity. METHODS: MtDNA was isolated
      from fresh goat liver and modified by ONOO(-), generated by synergistic action of
      nitric oxide (NO) and superoxide (O (-) 2) donors. Modifications occurring in
      mtDNA were characterized by physicochemical techniques. SLE patients (n = 50)
      with varying disease activity according to the SLE Disease Activity Index
      (SLEDAI) and healthy controls (n = 34) were evaluated for antibodies to native
      and ONOO(-)-modified mtDNA by immunoassays. Gel retardation assays were performed
      to cross-examine the immunoassay results using affinity-purified SLE
      immunoglobulin G (IgG). Nitrosative stress in SLE patients was studied by
      measuring nitrotyrosine and inducible NO synthase (iNOS). RESULTS: The ONOO(-)
      caused extensive damage to mtDNA as evident by ultraviolet (UV) hyperchromicity
      and loss of florescence intensity. Thermal melting studies, agarose gel
      electrophoresis and nuclease S1 digestibility clearly indicate structural
      perturbation in mtDNA by ONOO(-). Quenching studies with specific NO or O (-) 2
      quenchers confirmed that the damaging agent was ONOO(-). SLE autoantibodies
      exhibited enhanced binding with ONOO(-)-mtDNA as compared to their native analog.
      Interestingly, not only was there an increased number of subjects positive for
      ONOO(-) -mtDNA, but also the levels of anti-ONOO(-) -mtDNA antibodies were
      statistically significantly higher among SLE patients whose SLEDAI scores were >=
      20 as compared with SLE patients with lower SLEDAI scores (SLEDAI < 20). Normal
      healthy controls showed negligible binding with either antigen. Furthermore, SLE
      patients had higher levels of nitrotyrosine and iNOS compared with their
      respective healthy controls. CONCLUSIONS: Our novel results provide an important
      insight into the immunological basis of anti-DNA autoantibody generation in SLE.
      Our data conclude that modification of mtDNA by ONOO(-) causes structural
      perturbations, resulting in the generation of neo-epitopes, and making it a
      potential immunogen in SLE. The mtDNA modified by ONOO(-) may be useful in
      evaluating the progression of SLE and in elucidating the mechanisms of disease
      pathogenesis.

PMID- 23884989
TI  - Yet more knots in the radial artery, unravelling purely by counter clockwise
      rotation.
AB  - We describe here two more radial knots that could be unravelled by counter
      clockwise rotation alone. We and others have previously described radial knots
      that occur when trying to engage the right coronary artery (RCA). Here, we show
      two knots that were unravelled purely by counter-clockwise rotation. One occurred
      during RCA catheterisation and the other occurred during left coronary
      angiography via the radial route. In one of the patients, severe pain occurred in
      the right shoulder. This occurred even though the artery was not in spasm. We
      were able to move the catheter. Therefore it is possible that pain combined with
      the ability to move the catheter may be a marker of an intravascular knot. 

PMID- 23884990
TI  - Lancisi sign.

PMID- 23884991
TI  - The retrieval of the diagnostic catheter which broke and embolised twice.
AB  - We are presenting a nightmare case of successful retrieval of the broken distal
      tip of a multipurpose catheter which embolised into the left pulmonary artery
      (LPA) during atrial septal defect device closure. During the course of snaring it
      initially slipped once in the LPA and subsequently while snaring it into the
      delivery sheath it slipped again in the inferior vena cava and yet again
      embolised into the LPA!! Subsequent attempt was successful but the distal
      fragment itself broke into two parts while being pulled inside the delivery
      sheath. Luckily the fragments did not embolise again as they were stuck at the
      tip of the sheath. The distal fragments were pulled out en masse along with the
      delivery sheath maintaining negative pressure at the side port of the delivery
      sheath using a 20 mL syringe. The final outcome was successful and the patient
      was unharmed by this potentially grave complication. 

PMID- 23884992
TI  - Use of cell-free circulating schistosome DNA in serum, urine, semen, and saliva
      to monitor a case of refractory imported schistosomiasis hematobia.
AB  - This case of imported refractory schistosomiasis has highlighted the usefulness
      of cell-free parasite DNA as a diagnostic marker to assess active schistosome
      infection. In contrast to the rapid disappearance of ova in urine, parasite DNA
      remained persistent in several other specimen types even after the fourth
      treatment with praziquantel. This result was consistent with the presence of
      morphologically intact ova in bladder biopsy samples and with the corresponding
      symptoms. 

PMID- 23884993
TI  - Multidrug-resistant tuberculosis in panama is driven by clonal expansion of a
      multidrug-resistant Mycobacterium tuberculosis strain related to the KZN
      extensively drug-resistant M. tuberculosis strain from South Africa.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is a significant health problem in
      Panama. The extent to which such cases are the result of primary or acquired
      resistance and the strain families involved are unknown. We performed whole
      genome sequencing of a collection of 66 clinical MDR isolates, along with 31 drug
      susceptible isolates, that were isolated in Panama between 2001 and 2010; 78% of
      the MDR isolates belong to the Latin American-Mediterranean (LAM) family. Drug
      resistance mutations correlated well with drug susceptibility profiles. To
      determine the relationships among these strains and to better understand the
      acquisition of resistance mutations, a phylogenetic tree was constructed based on
      a genome-wide single-nucleotide polymorphism analysis. The phylogenetic tree
      shows that the isolates are highly clustered, with a single strain (LAM9-c1)
      accounting for nearly one-half of the MDR isolates (29/66 isolates). The LAM9-c1
      strain was most prevalent among male patients of working age and was associated
      with high mortality rates. Members of this cluster all share identical mutations
      conferring resistance to isoniazid (KatG S315T mutation), rifampin (RpoB S531L
      mutation), and streptomycin (rrs C517T mutation). This evidence of primary
      resistance supports a model in which MDR-TB in Panama is driven by clonal
      expansion and ongoing transmission of several strains in the LAM family,
      including the highly successful MDR strain LAM9-c1. The phylogenetic analysis
      also shows that the LAM9-c1 strain is closely related to the KwaZulu-Natal (KZN)
      extensively drug-resistant TB strain identified in KwaZulu-Natal, South Africa.
      The LAM9-c1 and KZN strains likely arose from a recent common ancestor that was
      transmitted between Panama and South Africa and had the capacity to tolerate an
      accumulation of multiple resistance mutations. 

PMID- 23884994
TI  - Phenotypic and molecular characterization of optochin-resistant Streptococcus
      pneumoniae isolates from Brazil, with description of five novel mutations in the
      ATPC gene.
AB  - Optochin (Opt) susceptibility is used largely for the identification of
      Streptococcus pneumoniae in diagnostic laboratories. Opt-resistant (Opt(r)) S.
      pneumoniae isolates have been reported, however, indicating the potential for
      misidentification of this important pathogen. Point mutations in the atpC gene
      have been associated with the emergence of Opt(r) S. pneumoniae, but data on the
      characterization of such atypical variants of S. pneumoniae are still limited.
      The present report describes the results of a polyphasic approach to identifying
      and characterizing 26 Opt(r) S. pneumoniae isolates recovered from patients or
      carriers living in Brazil. Sixteen isolates consisted of heterogeneous
      populations, and 10 isolates were homogeneously Opt(r). The isolates had
      different serotypes and antimicrobial susceptibility profiles. They also
      presented diverse genetic characteristics, as indicated by pulsed-field gel
      electrophoresis (PFGE), multilocus variable-number tandem-repeat analysis (MLVA),
      and pspA gene typing. Except for Opt MICs (4- to 64-fold higher among Opt(r)
      variants), Opt(r) and Opt-susceptible (Opt(s)) subpopulations originating from
      the same culture had identical characteristics. Sequencing of the atpC gene of
      the Opt(r) variants revealed 13 different nucleotide changes distributed among
      eight different codons. Changes in codon 49 were the most frequent, suggesting
      that this might be a hot spot for optochin resistance-conferring mutations. On
      the other hand, five novel types of mutations in the atpC gene (Met13Ile,
      Gly18Ser, Gly20Ala, Ala31Val, and Ala49Gly) were identified. In silico prediction
      modeling indicated that the atpC gene mutations corresponded to alterations in
      the transmembrane region of the ATPase, leading to a higher hydrophobicity
      profile in alpha-helix 1 and to a lower hydrophobicity profile in alpha-helix 2. 

PMID- 23884995
TI  - Rapid visual detection of highly pathogenic Streptococcus suis serotype 2
      isolates by use of loop-mediated isothermal amplification.
AB  - Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that
      causes considerable economic losses to the pig industry and significantly
      threatens public health worldwide. The highly pathogenic S. suis 2, which
      contains the 89K pathogenicity island (PAI), has caused large-scale outbreaks of
      infections in humans, resulting in high mortality rates. In this study, we
      established two loop-mediated isothermal amplification (LAMP)-based assays that
      can rapidly detect S. suis 2 and the 89K PAI and can be performed simultaneously
      under the same conditions. Further, based on the findings of these two LAMP
      assays and using the same set of serially diluted DNA samples, we compared the
      sensitivities of different LAMP product detection methods, including SYBR green
      detection, gel electrophoresis, turbidimetry, calcein assays, and hydroxynaphthol
      blue detection. The results suggest that target genes can be amplified and
      detected within 48 min under 63 degrees C isothermal conditions. The sensitivity
      of tests for S. suis 2 detection varies between detection methods and reaction
      systems, indicating that for each LAMP reaction system, multiple detection
      methods should be performed to select the optimal one. The sensitivities of the
      optimized methods (7.16 copies/reaction) in the present study were identical to
      those of the real-time PCR assay, and the test results for reference strains and
      clinical samples showed that these LAMP systems have high specificities. Thus,
      since the LAMP systems established in this study are simple, fast, and sensitive,
      they may have good clinical potential for detecting the highly pathogenic S. suis
      2. 

PMID- 23884996
TI  - Cardiac device-related endocarditis caused by Paenibacillus glucanolyticus.
AB  - We report the first case of Paenibacillus glucanolyticus infection in a 65-year
      old patient with type 2 diabetes who developed a cardiac device-related
      endocarditis. The identification of the isolate was performed using phenotypic
      methods, including mass spectrometry-based methods, and 16S rRNA gene sequencing.

PMID- 23884997
TI  - Discrimination of enterohemorrhagic Escherichia coli (EHEC) from non-EHEC strains
      based on detection of various combinations of type III effector genes.
AB  - Enterohemorrhagic Escherichia coli (EHEC) strains comprise a subgroup of Shiga
      toxin (Stx)-producing E. coli (STEC) and are characterized by a few serotypes.
      Among these, seven priority STEC serotypes (O26:H11, O45:H2, O103:H2, O111:H8,
      O121:H19, O145:H28, and O157:H7) are most frequently implicated in severe
      clinical illness worldwide. Currently, standard methods using stx, eae, and O
      serogroup-specific gene sequences for detecting the top 7 EHEC serotypes bear the
      disadvantage that these genes can be found in non-EHEC strains as well. Here, we
      explored the suitability of ureD, espV, espK, espN, Z2098, and espM1 genes and
      combinations thereof as candidates for a more targeted EHEC screening assay. For
      a very large panel of E. coli strains (n = 1,100), which comprised EHEC (n =
      340), enteropathogenic E. coli (EPEC) (n = 392), STEC (n = 193), and apathogenic
      strains (n = 175), we showed that these genetic markers were more prevalent in
      EHEC (67.1% to 92.4%) than in EPEC (13.3% to 45.2%), STEC (0.5% to 3.6%), and
      apathogenic E. coli strains (0 to 2.9%). It is noteworthy that 38.5% of the EPEC
      strains that tested positive for at least one of these genetic markers belonged
      to the top 7 EHEC serotypes, suggesting that such isolates might be Stx-negative
      derivatives of EHEC. The associations of espK with either espV, ureD, or Z2098
      were the best combinations for more specific and sensitive detection of the top 7
      EHEC strains, allowing detection of 99.3% to 100% of these strains. In addition,
      detection of 93.7% of the EHEC strains belonging to other serotypes than the top
      7 offers a possibility for identifying new emerging EHEC strains. 

PMID- 23884998
TI  - Survey of culture, goldengate assay, universal biosensor assay, and 16S rRNA Gene
      sequencing as alternative methods of bacterial pathogen detection.
AB  - Cultivation-based assays combined with PCR or enzyme-linked immunosorbent assay
      (ELISA)-based methods for finding virulence factors are standard methods for
      detecting bacterial pathogens in stools; however, with emerging molecular
      technologies, new methods have become available. The aim of this study was to
      compare four distinct detection technologies for the identification of pathogens
      in stools from children under 5 years of age in The Gambia, Mali, Kenya, and
      Bangladesh. The children were identified, using currently accepted clinical
      protocols, as either controls or cases with moderate to severe diarrhea. A total
      of 3,610 stool samples were tested by established clinical culture techniques:
      3,179 DNA samples by the Universal Biosensor assay (Ibis Biosciences, Inc.),
      1,466 DNA samples by the GoldenGate assay (Illumina), and 1,006 DNA samples by
      sequencing of 16S rRNA genes. Each method detected different proportions of
      samples testing positive for each of seven enteric pathogens, enteroaggregative
      Escherichia coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli
      (EPEC), Shigella spp., Campylobacter jejuni, Salmonella enterica, and Aeromonas
      spp. The comparisons among detection methods included the frequency of positive
      stool samples and kappa values for making pairwise comparisons. Overall, the
      standard culture methods detected Shigella spp., EPEC, ETEC, and EAEC in smaller
      proportions of the samples than either of the methods based on detection of the
      virulence genes from DNA in whole stools. The GoldenGate method revealed the
      greatest agreement with the other methods. The agreement among methods was higher
      in cases than in controls. The new molecular technologies have a high potential
      for highly sensitive identification of bacterial diarrheal pathogens. 

PMID- 23884999
TI  - Gordonia bacteremia.
AB  - Gordonia species are ubiquitous aerobic actinomycetes that rarely cause infection
      in humans. We report the second known case of Gordonia otitidis catheter-related
      bacteremia in an immunocompromised patient and review four additional cases of
      Gordonia bacteremia seen at our institution over the past 14 years. In addition,
      the existing literature on Gordonia infections is reviewed. 

PMID- 23885000
TI  - Evaluation of the Fluo-RAL module for detection of tuberculous and nontuberculous
      acid-fast Bacilli by fluorescence microscopy.

PMID- 23885001
TI  - Escherichia coli sequence type 131 as a prominent cause of antibiotic resistance
      among urinary Escherichia coli isolates from reproductive-age women.
AB  - The recent emergence of multidrug-resistant Escherichia coli sequence type 131
      (ST131) has coincided with an increase in general antibiotic resistance of E.
      coli, suggesting that ST131 has a contributing role in resistance. However, there
      is little information about the contribution of ST131 to different clinical
      syndromes or the basis for its impressive emergence and epidemic spread. To
      investigate this, we studied 953 E. coli isolates from women of reproductive age
      in the central west region of New South Wales, Australia, including 623 urinary
      isolates from patients with cystitis (cystitis isolates) (n = 322) or
      pyelonephritis (pyelonephritis isolates) (n = 301) and 330 fecal isolates from
      healthy controls. The characteristics studied included ST131 clonal group status,
      resistance to different antibiotics, presence of virulence factor (VF) genes, and
      biofilm production. As expected, fecal isolates differed significantly from
      urinary (cystitis and pyelonephritis) isolates in most of the studied
      characteristics. Antibiotic resistance was significantly more common in ST131
      than in non-ST131 isolates. Both antibiotic resistance and ST131 were more common
      in pyelonephritis than cystitis isolates and least so among fecal isolates.
      Within each source group, individual VF genes were more prevalent and VF scores
      were higher for ST131 than for non-ST131 isolates. For ST131 only, the
      prevalences of most individual VF genes and VF scores were the lowest in the
      fecal isolates, higher in the cystitis isolates, and highest in the
      pyelonephritis isolates. Biofilm production was strongly associated with ST131
      status and antibiotic resistance. These results clarify the distribution of the
      ST131 clonal group and its epidemiological associations in our region and suggest
      that it exhibits both enhanced virulence and increased antibiotic resistance
      compared with those of other urinary tract infection (UTI) and fecal E. coli
      isolates from women of reproductive age. 

PMID- 23885003
TI  - Multiple Streptococcus pneumoniae serotypes in aural discharge samples from
      children with acute otitis media with spontaneous otorrhea.
AB  - Among 55 children with cultures positive for acute otitis media with spontaneous
      otorrhea, 28 (51%) had cultures positive for aural Streptococcus pneumoniae, and
      in 10 of these, two distinct strains were detected, in which 5 had pairs of
      strains that were both capsule-bearing serotypes. Such cases were more likely to
      have cultures positive for other otopathogens than those with only one
      pneumococcus present. 

PMID- 23885002
TI  - Molecular studies neglect apparently gram-negative populations in the human gut
      microbiota.
AB  - Studying the relationships between gut microbiota, human health, and diseases is
      a major challenge that generates contradictory results. Most studies draw
      conclusions about the gut repertoire using a single biased metagenomics approach.
      We analyzed 16 different stool samples collected from healthy subjects who were
      from different areas, had metabolic disorders, were immunocompromised, or were
      treated with antibiotics at the time of the stool collection. The analyses
      performed included Gram staining, flow cytometry, transmission electron
      microscopy (TEM), quantitative real-time PCR (qPCR) of the Bacteroidetes and
      Firmicutes phyla, and pyrosequencing of the 16S rRNA gene amplicons targeting the
      V6 region. We quantified 10(10) prokaryotes per gram of feces, which is less than
      was previously described. The Mann-Whitney test revealed that Gram-negative
      proportions of the prokaryotes obtained by Gram staining, TEM, and pyrosequencing
      differed according to the analysis used, with Gram-negative prokaryotes yielding
      median percentages of 70.6%, 31.0%, and 16.4%, respectively. A comparison of TEM
      and pyrosequencing analyses highlighted a difference of 14.6% in the
      identification of Gram-negative prokaryotes, and a Spearman test showed a
      tendency toward correlation, albeit not significant, in the Gram-negative/Gram
      positive prokaryote ratio (rho = 0.3282, P = 0.2146). In contrast, when comparing
      the qPCR and pyrosequencing results, a significant correlation was found for the
      Bacteroidetes/Firmicutes ratio (rho = 0.6057, P = 0.0130). Our study showed that
      the entire diversity of the human gut microbiota remains unknown because
      different techniques generate extremely different results. We found that to
      assess the overall composition of bacterial communities, multiple techniques must
      be combined. The biases that exist for each technique may be useful in exploring
      the major discrepancies in molecular studies. 

PMID- 23885004
TI  - Nonsuppurative encephalomyelitis in a calf in Japan and isolation of Japanese
      encephalitis virus genotype 1 from the affected calf.
AB  - Japanese encephalitis virus (JEV) was isolated from the cerebrum of a calf which
      showed severe neurological symptoms in late September 2009, and the JEV isolate
      was revealed to be of genotype 1. This is the first report describing the
      isolation of genotype 1 JEV from cattle. 

PMID- 23885005
TI  - Evaluation of the Alfred 60/AST device as a screening test for urinary tract
      infections.
AB  - The performance of the Alfred 60/AST device, an automated bacterial culture
      device which uses laser nephelometry to detect and quantify bacterial growth, was
      evaluated. The instrument is effective at screening negative samples and is more
      reliable at detecting bacteria than yeasts. Microscopy can be used to reduce the
      false-negative numbers. 

PMID- 23885006
TI  - High-resolution melting curve analysis for rapid detection of rifampin resistance
      in Mycobacterium tuberculosis: a meta-analysis.
AB  - A rapid, simple, accurate, and affordable method for the detection of drug
      resistant tuberculosis is very critical for the selection of antimicrobial
      therapy and management of patient treatment. High-resolution melting curve
      analysis has been used for the detection of rifampin resistance in Mycobacterium
      tuberculosis and has shown promise. We did a systematic review and meta-analysis
      of published studies to evaluate the accuracy of high-resolution melting curve
      analysis for the detection of rifampin resistance in clinical M. tuberculosis
      isolates. We searched the PubMed, BIOSIS Previews, and Web of Science databases
      to identify studies and included them according to predetermined criteria. We
      used the DerSimonian-Laird random-effects model to calculate pooled measures and
      applied Moses' constant for linear models to fit the summary receiver operating
      characteristic curve. According to the selection criteria, most of the identified
      studies were excluded, and only seven studies were included in the final
      analysis. The overall sensitivity of the high-resolution melting curve analysis
      was 94% (95% confidence interval [CI], 92% to 96%), and the overall specificity
      was very high at 99% (95% CI, 98% to 100%). The values for the pooled positive
      likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 63.39
      (95% CI, 30.21 to 133.00), 0.06 (95% CI, 0.04 to 0.09), and 892.70 (95% CI,
      385.50 to 2,067.24), respectively. There was no significant heterogeneity across
      all included studies for the measurements we evaluated. The summary receiver
      operating characteristic curve for the same data shows an area of 0.99 and a Q*
      value of 0.97. High-resolution melting curve analysis has high sensitivity and
      specificity for the detection of rifampin resistance in clinical M. tuberculosis
      isolates. This method might be a good alternative to conventional drug
      susceptibility tests in clinical practice. 

PMID- 23885009
TI  - Availability of essential drugs for managing HIV-related pain and symptoms within
      120 PEPFAR-funded health facilities in East Africa: a cross-sectional survey with
      onsite verification.
AB  - BACKGROUND: World Health Organization's essential drugs list can control the
      highly prevalent HIV-related pain and symptoms. Availability of essential
      medicines directly influences clinicians' ability to effectively manage
      distressing manifestations of HIV. AIM: To determine the availability of pain and
      symptom controlling drugs in East Africa within President's Emergency Plan for
      AIDS Relief-funded HIV health care facilities. DESIGN: Directly observed
      quantitative health facilities' pharmacy stock review. We measured availability,
      expiration and stock-outs of specified drugs required for routine HIV management,
      including the World Health Organization pain ladder. SETTING: A stratified random
      sample in 120 President's Emergency Plan for AIDS Relief-funded HIV care
      facilities (referral and district hospitals, health posts/centres and home-based
      care providers) in Kenya and Uganda. RESULTS: Non-opioid analgesics (73%) and co
      trimoxazole (64%) were the most commonly available drugs and morphine (7%) the
      least. Drug availability was higher in hospitals and lower in health centres,
      health posts and home-based care facilities. Facilities generally did not use
      minimum stock levels, and stock-outs were frequently reported. The most common
      drugs had each been out of stock in the past 6 months in 47% of facilities
      stocking them. When a minimum stock level was defined, probability of a stock-out
      in the previous 6 months was 32.6%, compared to 45.5% when there was no defined
      minimum stock level (chi (2) = 5.07, p = 0.024). CONCLUSION: The data demonstrate
      poor essential drug availability, particularly analgesia, limited by facility
      type. The lack of strong opioids, isoniazid and paediatric formulations is
      concerning. Inadequate drug availability prevents implementation of simple
      clinical pain and symptom control protocols, causing unnecessary distress.
      Research is needed to identify supply chain mechanisms that lead to these
      problems.

PMID- 23885010
TI  - The palliative care needs for fibrotic interstitial lung disease: a qualitative
      study of patients, informal caregivers and health professionals.
AB  - BACKGROUND: While there have been some studies looking at the impact on quality
      of life of patients with idiopathic pulmonary fibrosis, to date no qualitative
      research looking at the specialist palliative needs of these patients has been
      conducted. AIM: This study aims to explore the specialist palliative care needs
      of people living with end-stage progressive idiopathic fibrotic interstitial lung
      disease. DESIGN AND SETTINGS/PARTICIPANTS: In total, 18 qualitative semi
      structured in-depth interviews were conducted with patients, their informal
      caregivers and health professionals across two specialist interstitial lung
      disease centres in London and in the community. RESULTS: Many participants
      reported uncontrolled symptoms of shortness of breath, cough and insomnia, which
      profoundly impacted every part of patients' and informal caregivers' lives.
      Psychologically, patients were frustrated and angry at the way in which their
      illness severely limited their ability to engage in activities of daily living
      and compromised their independence. Furthermore, both patients and informal
      caregivers also reported that the disease seriously affected family relationships
      where strain was pronounced. There was varied knowledge and confidence among
      health professionals in managing symptoms, and psychosocial needs were often
      underestimated. CONCLUSION: This study is the first of its kind to examine in
      depth the impact of symptoms and psychosocial needs revealing the profound effect
      on every aspect of progressive idiopathic fibrotic interstitial lung disease
      patients' and informal caregivers' lives. Education and guidance of appropriate
      palliative care interventions to improve symptom control are needed. A case
      conference intervention with individualised care plans may help in addressing the
      substantial symptom control and psychosocial needs of these patients and informal
      caregivers.

PMID- 23885011
TI  - After-hours physician care for patients with do-not-resuscitate orders: an
      observational cohort study.
AB  - BACKGROUND: Medical care at night for patients with do-not-resuscitate orders and
      the practice patterns of the on-call residents have rarely been reported. AIM: To
      evaluate the after-hours physician care for patients with do-not-resuscitate
      orders in the general medicine ward. DESIGN: Observational study.
      SETTING/PARTICIPANTS: This study was conducted at an urban, university-affiliated
      academic medical center in Taiwan. The night shift nurses consecutively recorded
      every event that required calling the duty residents. Patients with and without a
      do-not-resuscitate order were compared in demographics, reasons for calling,
      residents' response, and nurses' satisfaction. A standard report form was
      established for the nurses to record events. RESULTS: From October 2009 to
      September 2010, 1379 inpatients contributed to 456 after-hours calls. do-not
      resuscitate patients accounted for 256 (18.7%) of all inpatients, and 160 (35.1%)
      of all after-hours calls. The leading reason for calls was abnormal vital signs,
      which was significantly higher for patients with do-not-resuscitate orders
      compared to patients without a do-not-resuscitate order (64.4% vs 36.1%, p <
      0.001). The pattern of residents' responses showed a significant difference with
      more bedside visits for patients with do-not-resuscitate orders (p < 0.001). The
      nurses were usually satisfied with the residents' management of both groups.
      CONCLUSION: Abnormal vital sign, rather than symptom, was the leading reason for
      after-hours calls. The existence of do-not-resuscitate order produced different
      medical needs and physician workload. Patients with do-not-resuscitate orders
      accounted for one-third of night calls and nearly half of bedside visits by on
      call residents and may require a different care approach.

PMID- 23885012
TI  - Sex differences in metabolic and adipose tissue responses to juvenile-onset
      obesity in sheep.
AB  - Sex is a major factor determining adipose tissue distribution and the subsequent
      adverse effects of obesity-related disease including type 2 diabetes. The role of
      gender on juvenile obesity and the accompanying metabolic and inflammatory
      responses is not well established. Using an ovine model of juvenile onset obesity
      induced by reduced physical activity, we examined the effect of gender on
      metabolic, circulatory, and related inflammatory and energy-sensing profiles of
      the major adipose tissue depots. Despite a similar increase in fat mass with
      obesity between genders, males demonstrated a higher storage capacity of lipids
      within perirenal-abdominal adipocytes and exhibited raised insulin. In contrast,
      obese females became hypercortisolemic, a response that was positively correlated
      with central fat mass. Analysis of gene expression in perirenal-abdominal adipose
      tissue demonstrated the stimulation of inflammatory markers in males, but not
      females, with obesity. Obese females displayed increased expression of genes
      involved in the glucocorticoid axis and energy sensing in perirenal-abdominal,
      but not omental, adipose tissue, indicating a depot-specific mechanism that may
      be protective from the adverse effects of metabolic dysfunction and inflammation.
      In conclusion, young males are at a greater risk than females to the onset of
      comorbidities associated with juvenile-onset obesity. These sex-specific
      differences in cortisol and adipose tissue could explain the earlier onset of the
      metabolic-related diseases in males compared with females after obesity. 

PMID- 23885013
TI  - Evidence for the regulatory role of lipocalin 2 in high-fat diet-induced adipose
      tissue remodeling in male mice.
AB  - Lipocalin 2 (Lcn2) has previously been characterized as an adipokine/cytokine
      playing a role in glucose and lipid homeostasis. In this study, we investigate
      the role of Lcn2 in adipose tissue remodeling during high-fat diet (HFD)-induced
      obesity. We find that Lcn2 protein is highly abundant selectively in inguinal
      adipose tissue. During 16 weeks of HFD feeding, the inguinal fat depot expanded
      continuously, whereas the expansion of the epididymal fat depot was reduced in
      both wild-type (WT) and Lcn2(-/-) mice. Interestingly, the depot-specific effect
      of HFD on fat mass was exacerbated and appeared more pronounced and faster in
      Lcn2(-/-) mice than in WT mice. In Lcn2(-/-) mice, adipocyte hypertrophy in both
      inguinal and epididymal adipose tissue was more profoundly induced by age and HFD
      when compared with WT mice. The expression of peroxisome proliferator-activated
      receptor-gamma protein was significantly down-regulated, whereas the gene
      expression of extracellular matrix proteins was up-regulated selectively in
      epididymal adipocytes of Lcn2(-/-) mice. Consistent with these observations,
      collagen deposition was selectively higher in the epididymal, but not in the
      inguinal adipose depot of Lcn2(-/-) mice. Administration of the peroxisome
      proliferator-activated receptor-gamma agonist rosiglitazone (Rosi) restored
      adipogenic gene expression. However, Lcn2 deficiency did not alter the
      responsiveness of adipose tissue to Rosi effects on the extracellular matrix
      expression. Rosi treatment led to the further enlargement of adipocytes with
      improved metabolic activity in Lcn2(-/-) mice, which may be associated with a
      more pronounced effect of Rosi treatment in reducing TGF-beta in Lcn2(-/-)
      adipose tissue. Consistent with these in vivo observations, Lcn2 deficiency
      reduces the adipocyte differentiation capacity of stromal-vascular cells isolated
      from HFD-fed mice in these cells. Herein Rosi treatment was again able to
      stimulate adipocyte differentiation to a similar extent in WT and Lcn2(-/-)
      inguinal and epididymal stromal-vascular cells. Thus, combined, our data indicate
      that Lcn2 has a depot-specific role in HFD-induced adipose tissue remodeling. 

PMID- 23885016
TI  - In vivo knockdown of adipocyte erythropoietin receptor does not alter glucose or
      energy homeostasis.
AB  - The growing prevalence of obesity and diabetes necessitate a better understanding
      of the role of adipocyte biology in metabolism. Increasingly, erythropoietin
      (EPO) has been shown to have extraerythropoietic and cytoprotective roles.
      Exogenous administration has recently been shown to have beneficial effects on
      obesity and diabetes in mouse models and EPO can modulate adipogenesis and
      insulin signaling in 3T3-L1 adipocytes. However, its physiological role in
      adipocytes has not been identified. Using male and female mice with adipose
      tissue-specific knockdown of the EPO receptor, we determine that adipocyte EPO
      signaling is not essential for the maintenance of energy homeostasis or glucose
      metabolism. Adipose tissue-specific disruption of EPO receptor did not alter
      adipose tissue expansion, adipocyte morphology, insulin resistance, inflammation,
      or angiogenesis in vivo. In contrast to the pharmacological effects of EPO, we
      demonstrate that EPO signaling at physiological levels is not essential for
      adipose tissue regulation of metabolism. 

PMID- 23885014
TI  - Obesity and insulin resistance induce early development of diastolic dysfunction
      in young female mice fed a Western diet.
AB  - Cardiovascular disease (CVD), including heart failure, constitutes the main
      source of morbidity and mortality in men and women with diabetes. Although
      healthy young women are protected against CVD, postmenopausal and diabetic women
      lose this CVD protection. Obesity, insulin resistance, and diabetes promote heart
      failure in females, and diastolic dysfunction is the earliest manifestation of
      this heart failure. To examine the mechanisms promoting diastolic dysfunction in
      insulin-resistant females, this investigation evaluated the impact of 8 weeks of
      a high-fructose/high-fat Western diet (WD) on insulin sensitivity and cardiac
      structure and function in young C57BL6/J female versus male mice. Insulin
      sensitivity was determined by hyperinsulinemic-euglycemic clamps and two
      dimensional echocardiograms were used to evaluate cardiac function. Both males
      and females developed systemic insulin resistance after 8 weeks of a WD. However,
      only the females developed diastolic dysfunction. The diastolic dysfunction
      promoted by the WD was accompanied by increases in collagen 1, a marker of
      stiffness, increased oxidative stress, reduced insulin metabolic signaling, and
      increased mitochondria and cardiac microvascular alterations as determined by
      electron microscopy. Aldosterone (a promoter of cardiac stiffness) levels were
      higher in females compared with males but were not affected by the WD in either
      gender. These data suggest a predisposition toward developing early diastolic
      heart failure in females exposed to a WD. These data are consistent with the
      notion that higher aldosterone levels, in concert with insulin resistance, may
      promote myocardial stiffness and diastolic dysfunction in response to
      overnutrition in females. 

PMID- 23885021
TI  - Oropharyngeal dysphagia in an elderly post-operative hip fracture population.
AB  - Love et al (2013) claim new findings linking intervention for hip fracture with
      dysphagia. This commentary reflects on whether this represents novel data or
      simply reiterates previously recognised patterns, not necessarily specific to
      surgical hip-repair. Issues are addressed in the context of prevalence of
      dysphagia in community and care-home living older people; effects of operative
      procedures on swallowing; methods for screening for dysphagia; and methodological
      decisions made by Love et al. The role of dysphagia screening policies is briefly
      considered. 

PMID- 23885015
TI  - Effects of the selective glucocorticoid receptor modulator compound A on bone
      metabolism and inflammation in male mice with collagen-induced arthritis.
AB  - Glucocorticoids (GCs) are potent drugs to treat rheumatoid arthritis but exert
      adverse skeletal effects. Compound A (CpdA) is a selective GC receptor modulator
      with an improved risk/benefit profile in mouse models of inflammation and bone
      loss. Here we tested whether CpdA also exerts bone-sparing effects under
      proinflammatory circumstances using the collagen-induced arthritis model, a
      murine model of rheumatoid arthritis. CpdA decreased disease activity, paw
      swelling, and the paw temperature by 43%, 12%, and 7%, respectively, but was less
      potent than dexamethasone (DEX), which reduced these parameters by 72%, 22%, and
      10%, respectively. Moreover, T cells isolated from CpdA- and DEX-treated animals
      were less active based on proliferation rates after challenge with type II
      collagen and produced smaller amounts of interferon-gamma and TNF as compared
      with T cells from PBS-treated mice. Histological assessment of the joints
      confirmed the weaker potency of CpdA as compared with DEX in preventing
      infiltration of inflammatory cells, induction of osteoclastogenesis, and
      destruction of articular cartilage. Due to the lack of GC-susceptible arthritis
      models, we were not able to fully address the bone-sparing potential of CpdA in
      inflammatory conditions. Nevertheless, the bone formation marker procollagen type
      1 N-terminal peptide, a surrogate marker for GC-mediated suppression of bone
      formation, was significantly decreased by DEX in arthritic mice but not by CpdA.
      Our data indicate that CpdA moderately suppresses inflammation, whereas the
      concurrent effects on bone remain unknown. In light of its narrow therapeutic
      range, CpdA may be more useful as a molecular tool for dissecting GC actions
      rather than a therapeutic agent. 

PMID- 23885020
TI  - GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in
      enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric
      leukocytes.
AB  - The expression of short-chain fatty acid receptors GPR41/FFAR3 and GPR43/ free
      fatty acid receptor 2 (FFAR2) was studied in the gastrointestinal tract of
      transgenic monomeric red fluorescent protein (mRFP) reporter mice. In the stomach
      free fatty acid receptor 3 (FFAR3)-mRFP was expressed in a subpopulation of
      ghrelin and gastrin cells. In contrast, strong expression of FFAR3-mRFP was
      observed in all cholecystokinin, glucose-dependent insulinotropic peptide (GIP),
      and secretin cells of the proximal small intestine and in all glucagon-like
      peptide-1 (GLP-1), peptide YY, and neurotensin cells of the distal small
      intestine. Throughout the colon and rectum, FFAR3-mRFP was strongly expressed in
      the large population of peptide YY and GLP-1 cells and in the neurotensin cells
      of the proximal colon. A gradient of expression of FFAR3-mRFP was observed in the
      somatostatin cells from less than 5% in the stomach to more than 95% in the
      rectum. Substance P-containing enterochromaffin cells displayed a similar
      gradient of FFAR3-mRFP expression throughout the small intestine. Surprisingly,
      FFAR3-mRFP was also expressed in the neuronal cells of the submucosal and
      myenteric ganglia. Quantitative PCR analysis of fluorescence-activated cell
      sorting (FACS) purified FFAR3-mRFP positive cells confirmed the coexpression with
      the various peptide hormones as well as key neuronal marker proteins. The FFAR2
      mRFP reporter was strongly expressed in a large population of leukocytes in the
      lamina propria of in particular the small intestine but surprisingly only weakly
      in a subpopulation of enteroendocrine cells. Nevertheless, synthetic ligands
      specific for either FFAR3 or FFAR2 each released GLP-1 from colonic crypt
      cultures and the FFAR2 agonist mobilized intracellular Ca2+ in FFAR2 positive
      enteroendocrine cells. It is concluded that FFAR3-mRFP serves as a useful marker
      for the majority of enteroendocrine cells of the small and large intestine and
      that FFAR3 and FFAR2 both act as sensors for short-chain fatty acids in
      enteroendocrine cells, whereas FFAR3 apparently has this role alone in enteric
      neurons and FFAR2 in enteric leukocytes.

PMID- 23885022
TI  - Superior neurologic recovery after 15 minutes of normothermic cardiac arrest
      using an extracorporeal life support system for optimized blood pressure and
      flow.
AB  - OBJECTIVE: Sudden cardiac arrest is one of the leading causes of death.
      Conventional CPR techniques after cardiac arrest provide circulation with reduced
      and varying blood flow and pressure. We hypothesize that using pressure- and flow
      controlled reperfusion of the whole body improves neurological recovery and
      survival after 15 min of normothermic cardiac arrest. METHODS: Pigs were
      randomized in two experimental groups and exposed to 15 min of ventricular
      fibrillation (VF). After this period, the animals in the control group received
      conventional CPR with open chest compression (n=6), while circulation in the
      treatment group (n=6) was established with an extracorporeal life support system
      (ECLS) to control blood pressure and flow. Follow-up included the assessment of
      neurological recovery and magnetic resonance imaging (MRI) for up to 7 days.
      RESULTS: Five of the six animals in the control group died, one animal was
      resuscitated successfully. In the treatment group, 1/6 could not be separated
      from ECLS. Five out of the six pigs survived and were transferred to the animal
      facility. One animal was unable to walk and had to be sacrificed 30 hours after
      ECLS. The remaining 4 animals of the treatment group and the surviving pig from
      the control group showed complete neurological recovery. Brain MRI revealed no
      pathological changes. CONCLUSION: We were able to demonstrate a significant
      improvement in survival after 15 minutes of normothermic cardiac arrest. These
      results support our hypothesis that using an ECLS for pressure- and flow
      controlled circulation after circulatory arrest is superior to conventional CPR.

PMID- 23885019
TI  - TFE3 controls lipid metabolism in adipose tissue of male mice by suppressing
      lipolysis and thermogenesis.
AB  - Transcription factor E3 (TFE3) is a transcription factor that binds to E-box
      motifs and promotes energy metabolism-related genes. We previously reported that
      TFE3 directly binds to the insulin receptor substrate-2 promoter in the liver,
      resulting in increased insulin response. However, the role of TFE3 in other
      tissues remains unclear. In this study, we generated adipose-specific TFE3
      transgenic (aP2-TFE3 Tg) mice. These mice had a higher weight of white adipose
      tissue (WAT) and brown adipose tissue than wild-type (WT) mice under fasting
      conditions. Lipase activity in the WAT in these mice was lower than that in the
      WT mice. The mRNA level of adipose triglyceride lipase (ATGL), the rate-limiting
      enzyme for adipocyte lipolysis, was significantly decreased in aP2-TFE3 Tg mice.
      The expression of Foxo1, which directly activates ATGL expression, was also
      suppressed in transgenic mice. Promoter analysis confirmed that TFE3 suppressed
      promoter activities of the ATGL gene. In contrast, G0S2 and Perilipin1, which
      attenuate ATGL activity, were higher in transgenic mice than in WT mice. These
      results indicated that the decrease in lipase activity in adipose tissues was due
      to a decrease in ATGL expression and suppression of ATGL activity. We also showed
      that thermogenesis was suppressed in aP2-TFE3 Tg mice. The decrease in lipolysis
      in WAT of aP2-TFE3 Tg mice inhibited the supply of fatty acids to brown adipose
      tissue, resulting in the inhibition of the expression of thermogenesis-related
      genes such as UCP1. Our data provide new evidence that TFE3 regulates lipid
      metabolism by controlling the gene expression related to lipolysis and
      thermogenesis in adipose tissue. 

PMID- 23885017
TI  - ROCK1 in AgRP neurons regulates energy expenditure and locomotor activity in male
      mice.
AB  - Normal leptin signaling is essential for the maintenance of body weight
      homeostasis. Proopiomelanocortin- and agouti-related peptide (AgRP)-producing
      neurons play critical roles in regulating energy metabolism. Our recent work
      demonstrates that deletion of Rho-kinase 1 (ROCK1) in the AgRP neurons of mice
      increased body weight and adiposity. Here, we report that selective loss of ROCK1
      in AgRP neurons caused a significant decrease in energy expenditure and locomotor
      activity of mice. These effects were independent of any change in food intake.
      Furthermore, AgRP neuron-specific ROCK1-deficient mice displayed central leptin
      resistance, as evidenced by impaired Signal Transducer and Activator of
      Transcription 3 activation in response to leptin administration. Leptin's ability
      to hyperpolarize and decrease firing rate of AgRP neurons was also abolished in
      the absence of ROCK1. Moreover, diet-induced and genetic forms of obesity
      resulted in reduced ROCK1 activity in murine arcuate nucleus. Of note, high-fat
      diet also impaired leptin-stimulated ROCK1 activity in arcuate nucleus,
      suggesting that a defect in hypothalamic ROCK1 activity may contribute to the
      pathogenesis of central leptin resistance in obesity. Together, these data
      demonstrate that ROCK1 activation in hypothalamic AgRP neurons is required for
      the homeostatic regulation of energy expenditure and adiposity. These results
      further support previous work identifying ROCK1 as a key regulator of energy
      balance and suggest that targeting ROCK1 in the hypothalamus may lead to
      development of antiobesity therapeutics. 

PMID- 23885018
TI  - The opposing roles of nitric oxide and cGMP in the age-associated decline in rat
      testicular steroidogenesis.
AB  - The molecular mechanism of the aging-associated dysfunction of Leydig cells (LCs)
      is complex and poorly understood. In this study, we analyzed the contribution of
      nitric oxide (NO) and cGMP signaling to the age-dependent decline in LC function.
      Significant (>50%) decreases in serum, intratesticular, and LC androgens in aging
      rats (15-24 months) were accompanied by a proportional increase in NO production,
      an up-regulation of cGMP levels, and the expression of soluble guanylyl cyclase
      1B and protein kinase G1 in LCs. In contrast, LC cAMP levels decreased with age,
      most likely reflecting the up-regulation of cAMP-specific phosphodiesterase
      expression. Moreover, the expression of genes encoding enzymes responsible for
      cholesterol transport and its conversion to T were reduced. Exposing LCs from
      aged animals to NO further increased cGMP levels and decreased cAMP and androgen
      production, whereas the addition of cell-permeable 8-bromoguanosine-cGMP alone
      had the opposite effect. In vivo inhibition of cGMP-specific phosphodiesterase-5
      for 3 and 6 months in aged rats led to a partial restoration of androgens, NO,
      and cyclic nucleotide levels, as well as the expression of steroidogenic and
      NO/cGMP signaling genes. These results indicate that a progressive increase in NO
      production contributes to the age-dependent decrease in steroidogenesis in a cGMP
      independent manner, whereas the sustained elevation in cGMP levels significantly
      slows the decline in LC function. 

PMID- 23885023
TI  - Factorial designs: an overview with applications to orthodontic clinical trials.
AB  - Factorial designs for clinical trials are often encountered in medical, dental,
      and orthodontic research. Factorial designs assess two or more interventions
      simultaneously and the main advantage of this design is its efficiency in terms
      of sample size as more than one intervention may be assessed on the same
      participants. However, the factorial design is efficient only under the
      assumption of no interaction (no effect modification) between the treatments
      under investigation and, therefore, this should be considered at the design
      stage. Conversely, the factorial study design may also be used for the purpose of
      detecting an interaction between two interventions if the study is powered
      accordingly. However, a factorial design powered to detect an interaction has no
      advantage in terms of the required sample size compared to a multi-arm parallel
      trial for assessing more than one intervention. It is the purpose of this article
      to highlight the methodological issues that should be considered when planning,
      analysing, and reporting the simplest form of this design, which is the 2 * 2
      factorial design. An example from the field of orthodontics using two parameters
      (bracket type and wire type) on maxillary incisor torque loss will be utilized in
      order to explain the design requirements, the advantages and disadvantages of
      this design, and its application in orthodontic research.

PMID- 23885025
TI  - The Public Health Responsibility Deal: how should such a complex public health
      policy be evaluated?
AB  - BACKGROUND: The Public Health Responsibility Deal (RD) in England was launched in
      2011 as a public-private partnership which aims to 'tap into the potential for
      businesses and other influential organisations to make a significant contribution
      to improving public health by helping us to create this environment'. It has come
      under criticism from public health advocates and others, who have suggested that
      it will be ineffective or perhaps even harmful. Like many public health policies,
      there have also been demands to know whether it 'works'. METHODS: We conducted a
      scoping review and used this, supplemented with interviews with stakeholders, to
      develop a detailed logic model of the RD (presented here) to help understand its
      likely outcomes and the pathways by which these may be achieved as a basis for
      planning an evaluation. CONCLUSIONS: Evaluations of complex interventions require
      not just assessment of effects (including outcomes), but also a clear
      conceptualization of the intervention and its processes. The way the RD and the
      pledges made by participant organizations has been presented makes it difficult
      at this stage to evaluate whether the RD 'works' in terms of improving health.
      Instead, any evaluation needs to put together a jigsaw of evidence about
      processes, mechanisms and potential future health and non-health impacts, in part
      using the current scientific evidence. This task is ongoing.

PMID- 23885026
TI  - Distance to screening site and non-participation in screening for breast cancer:
      a population-based study.
AB  - BACKGROUND: In population-based breast cancer screening programmes, the
      geographical distance to the screening site may influence a woman's propensity to
      participate. The aim of this study was to analyse the effect driving distance to
      the screening unit had on women's participation in a breast cancer screening
      programme. METHODS: All women invited to the first round of breast cancer
      screening in the Central Denmark Region were eligible for inclusion (n =
      149,234). Information on participation was collected from a regional
      administrative database. The shortest road distance between each woman's
      residence and her affiliated screening site was assessed using Network Analyst,
      ArcGIS. RESULTS: The unadjusted association between distance and non
      participation formed a J-shape curve. Adjustment for socio-demographic
      characteristics caused the J-shape to disappear, and the probability of non
      attendance rose with longer distance to the screening site but flattened after
      ~45 km. Women without access to a vehicle had a higher risk of non-participation
      than women with access to a vehicle. CONCLUSIONS: A long road distance to the
      screening site was associated with an increased risk of non-participation. Women
      without access to a vehicle were at higher risk of non-participation than women
      who had access to a vehicle.

PMID- 23885027
TI  - A single intraduodenal administration of human adenovirus 40 vaccine effectively
      prevents anaphylactic shock.
AB  - Vaccine administration into the intestine is known to induce mucosal tolerance
      most efficiently. Therefore, developing a delivery system that targets the
      intestinal mucosa is expected to improve the efficiency of immunosuppression.
      Human enteric adenovirus serotype 40 (Ad40)-based vectors have the advantage of
      targeting intestinal mucosa, making them prime candidates as mucosal vaccine
      carriers for immunosuppression. Here, after both oral and intraduodenal
      administrations, the vector distribution of replication-defective recombinant
      Ad40 vectors (rAd40) was significantly higher than that of a conventional Ad
      vector based on human adenovirus 5 (Ad5) in ilea containing Peyer's patches.
      Single intraduodenal administration of rAd40 induced antigen-specific mucosal
      immunoreaction mediated by intestinal mucosal and systemic immunity. In ovalbumin
      induced allergy mouse models, this approach inhibited antigen-specific delayed
      type hypersensitivity reactions, diarrhea occurrence, and systemic anaphylaxis.
      Thus, a single intraduodenal administration of rAd40 provides a potent method of
      inducing allergen-specific mucosal tolerance and a new allergen-specific
      immunotherapy for overcoming problems with current therapies against life
      threatening allergic reactions, including anaphylaxis. 

PMID- 23885029
TI  - Rapid, sensitive recovery of recombinant attenuated Salmonella enterica serovar
      Typhi vaccine strains from human blood.
AB  - Prior to initiating a phase 1 dose escalation trial of the safety and
      immunogenicity of live, oral, recombinant, attenuated Salmonella enterica serovar
      Typhi vaccine strains in human subjects, the suitability of conventional blood
      culture procedures to rapidly and reliably detect the organisms in human blood
      was investigated. Blood culture specimens, with and without added growth
      supplements, were inoculated with study organism concentrations ranging from
      approximately 300 to as few as 1 to 2 CFU/10 ml culture and processed in a Bactec
      9240 fluorescent series aerobic blood culture system. All cultures seeded with >6
      CFU and 93% of cultures seeded with ~1 to 2 CFU were identified as positive for
      microbial growth within 44 h of incubation. The results were within the
      performance standard of <=5 days to detection that is expected for Gram-negative
      cultures seeded at 10 to 50 CFU/vial. Recovery of test organisms from blood
      culture was not improved by the addition of supplements, but cultures with added
      supplements were identified positive an average of 5 h sooner than those without
      added supplements. Reliable detection of the investigational vaccine strains at
      <1 CFU/ml of blood within 2 days in conventional blood culture without added
      supplements allowed for shortened confinement time of study volunteers without
      compromising subject safety. 

PMID- 23885024
TI  - "I'm not just a heart, I'm a whole person here": a qualitative study to improve
      sexual outcomes in women with myocardial infarction.
AB  - BACKGROUND: Little is known about recovery of female sexual function following an
      acute myocardial infarction (MI). Interventions to improve sexual outcomes in
      women are limited. METHODS AND RESULTS: Semistructured, qualitative telephone
      interviews were conducted with 17 partnered women (aged 43 to 75 years)
      purposively selected from the Translational Research Investigating Underlying
      Disparities in Acute Myocardial Infarction Patients' Health Status Registry to
      deepen knowledge of recovery of female sexual function following an acute
      myocardial infarction (MI) and to improve sexual outcomes in women. Sixteen women
      had a monogamous relationship with a male spouse; 1 had a long-term female
      partner. Most women resumed sexual activity within 4 weeks of their MI. Sexual
      problems and concerns were prevalent, including patient and/or partner fear of
      "causing another heart attack." Few women received counseling about sexual
      concerns or the safety of returning to sex. Most women who discussed sex with a
      physician initiated the discussion themselves. Inquiry about strategies to
      improve sexual outcomes elicited key themes: need for privacy, patient
      centeredness, and information about the timing and safe resumption of sexual
      activity. In addition, respondents felt that counseling should be initiated by
      the treating cardiologist, who "knows whether your heart is safe," and then
      reinforced by the care team throughout the rehabilitation period. CONCLUSIONS:
      Partnered women commonly resume sexual activity soon after an MI with fear but
      without directed counseling from their physicians. Proactive attention to women's
      concerns related to sexual function and the safety of sexual activity following
      an MI could improve post-MI outcomes for women and their partners.

PMID- 23885031
TI  - Acute disseminated encephalomyelitis following seasonal influenza vaccination in
      an elderly patient.
AB  - Although such occurrences are rare, it should be recognized that certain vaccines
      might trigger serious neurological immune phenomena such as Guillain-Barre
      syndrome, seizures, cranial neuropathy, and acute disseminated encephalomyelitis
      (ADEM). Here we report on an elderly woman with ADEM following seasonal influenza
      vaccination who recovered after plasma exchange. 

PMID- 23885030
TI  - Virulence, transmission, and heterologous protection of four isolates of
      Haemophilus parasuis.
AB  - Haemophilus parasuis causes Glasser's disease, a syndrome of polyserositis,
      meningitis, and arthritis in swine. Previous studies with H. parasuis have
      revealed virulence disparity among isolates and inconsistent heterologous
      protection. In this study, virulence, direct transmission, and heterologous
      protection of 4 isolates of H. parasuis (SW114, 12939, MN-H, and 29755) were
      evaluated using a highly susceptible pig model. In an initial experiment,
      isolates 12939, MN-H, and 29755 caused Glasser's disease, while strain SW114
      failed to cause any clinical signs of disease. One pig from each group challenged
      with MN-H or 29755 failed to develop clinical disease but was able to transmit H.
      parasuis to noninfected pigs, which subsequently developed Glasser's disease.
      Pigs colonized with SW114, 29755, or MN-H that were free of clinical disease were
      protected from a subsequent challenge with isolate 12939. In a following
      experiment, pigs vaccinated with strain SW114 given as either a bacterin
      intramuscularly or a live intranasal vaccine were protected from subsequent
      challenge with isolate 12939; however, some pigs given live SW114 developed
      arthritis. Overall these studies demonstrated that pigs infected with virulent
      isolates of H. parasuis can remain healthy and serve as reservoirs for
      transmission to naive pigs and that heterologous protection among H. parasuis
      isolates is possible. In addition, further attenuation of strain SW114 is
      necessary if it is to be used as a live vaccine. 

PMID- 23885032
TI  - Flow cytometric detection of Mycobacterium avium subsp. paratuberculosis-specific
      antibodies in experimentally infected and naturally exposed calves.
AB  - A desirable test to diagnose infections with Mycobacterium avium subsp.
      paratuberculosis facilitates identification of infected cattle prior to the state
      of M. avium subsp. paratuberculosis shedding. This study aimed at adjusting a
      flow cytometry (FC)-based assay, using intact M. avium subsp. paratuberculosis
      bacteria as the antigen, for diagnosis of M. avium subsp. paratuberculosis
      infections in calves. Serum samples were collected from experimentally infected
      (n = 12) and naturally exposed (n = 32) calves. Samples from five calves from
      positive dams were analyzed to determine the dynamics of maternal antibodies.
      Samples from adult cattle with defined infection status served as the standard
      (18 M. avium subsp. paratuberculosis shedders, 22 M. avium subsp.
      paratuberculosis free). After preadsorption with Mycobacterium phlei, sera were
      incubated with M. avium subsp. paratuberculosis and M. avium subsp. avium
      bacterial suspensions, respectively, followed by the separate detection of bovine
      IgG, IgG1, IgG2, and IgM attached to the bacterial surface. M. avium subsp.
      paratuberculosis-specific sample/positive (S/P) ratios were compared to enzyme
      linked immunosorbent assay (ELISA) S/P ratios. In adult cattle, the FC assay for
      IgG1 had a sensitivity of 78% at a specificity of 100%. Maternally acquired
      antibodies could be detected in calves up to 121 days of life. While all but two
      sera taken at day 100 +/- 10 postnatum from naturally exposed calves tested
      negative, elevated S/P ratios (IgG and IgG1) became detectable from 44 and 46
      weeks postinoculation onwards in two calves infected experimentally. Even with
      the optimized FC assay, M. avium subsp. paratuberculosis-specific antibodies can
      only occasionally be detected in infected calves less than 12 months of age. The
      failure to detect such antibodies apparently reflects the distinct immunobiology
      of M. avium subsp. paratuberculosis infections rather than methodological
      constraints. 

PMID- 23885034
TI  - Touch as an interpersonal emotion regulation process in couples' daily lives: the
      mediating role of psychological intimacy.
AB  - Interpersonal touch seems to promote physical health through its effects on
      stress-sensitive parameters. However, less is known about the psychological
      effects of touch. The present study investigates associations between touch and
      romantic partners' affective state in daily life. We hypothesized that this
      association is established by promoting the recipient's experience of intimacy.
      Both partners of 102 dating couples completed an electronic diary 4 times a day
      during 1 week. Multilevel analyses revealed that touch was associated with
      enhanced affect in the partner. This association was mediated by the partner's
      psychological intimacy. Touch was also associated with intimacy and positive
      affect in the actor. Finally, participants who were touched more often during the
      diary study week reported better psychological well-being 6 months later. This
      study provides evidence that intimate partners benefit from touch on a
      psychological level, conveying a sense of strengthened bonds between them that
      enhances affect and well-being. 

PMID- 23885036
TI  - When visibility matters: short-term versus long-term costs and benefits of
      visible and invisible support.
AB  - Sixty-one couples engaged in two video-recorded discussions in which one partner
      (the support recipient) discussed a personal goal with the other partner (the
      support provider). The support provider's visible and invisible support behaviors
      were coded by independent raters. Measures of perceived support, discussion
      success, and support recipients' distress during the discussion were gathered.
      Recipients also reported their goal achievement at 3-month intervals over the
      following year. Greater visible emotional support was associated with greater
      perceived support and discussion success for highly distressed recipients, but it
      was costly for nondistressed recipients who reported lower discussion success. In
      contrast, greater invisible emotional support was not associated with perceived
      support or discussion success, but it predicted greater goal achievement across
      time. These results advance our current understanding of support processes by
      indicating that the costs and benefits of visible support hinge on recipients'
      needs, whereas invisible support shapes recipients' long-term goal achievement. 

PMID- 23885035
TI  - The things you do for me: perceptions of a romantic partner's investments promote
      gratitude and commitment.
AB  - Although a great deal of attention has been paid to the role of people's own
      investment in promoting relationship commitment, less research has considered the
      possible role of the partner's investments. An experiment (Study 1) and two
      combined daily experience and longitudinal studies (Studies 2 and 3) documented
      that perceived investments from one partner motivate the other partner to further
      commit to the relationship. All three studies provided support for gratitude as a
      mechanism of this effect. These effects held even for individuals who were
      relatively less satisfied with their relationships. Together, these results
      suggest that people feel particularly grateful for partners who they perceive to
      have invested into the relationship, which, in turn, motivates them to further
      commit to the relationship. Implications for research and theory on gratitude and
      relationship commitment are discussed. 

PMID- 23885028
TI  - A suppressor of cytokine signaling 1 antagonist enhances antigen-presenting
      capacity and tumor cell antigen-specific cytotoxic T lymphocyte responses by
      human monocyte-derived dendritic cells.
AB  - The suppressor of cytokine signaling 1 (SOCS1) has emerged as a critical
      inhibitory molecule for controlling the cytokine response and antigen
      presentation by dendritic cells (DCs), thereby regulating the magnitude of both
      innate and adaptive immunity. The aim of this study was to investigate whether
      the SOCS1 antagonist pJAK2(1001-1013) peptide can weaken or block the inhibition
      function of SOCS1 in DCs by evaluating the phenotype and cytokine production,
      antigen-presenting, and specific T-cell-activating capacities of DCs
      electroporated with human gastric cancer cell total RNA. Furthermore, STAT1
      activation of the JAK/STAT signal pathway mediated by SOCS1 was analyzed by
      Western blotting. The results demonstrate that the SOCS1 antagonist pJAK2(1001
      1013) peptide upregulated the expression of the maturation marker (CD83) and
      costimulatory molecule (CD86) of RNA-electroporated human monocyte-derived mature
      DCs (mDCs), potentiated the capacity of mDCs to induce T-cell proliferation,
      stimulated the secretion of proinflammatory cytokines, and enhanced the
      cytotoxicity of tumor cell antigen-specific CTLs activated by human gastric
      cancer cell total RNA-electroporated mDCs. Data from Western blot analysis
      indicate that STAT1 was further activated in pJAK2(1001-1013) peptide-loaded
      mDCs. These results imply that the SOCS1 antagonist pJAK2(1001-1013) peptide is
      an effective reagent for the enhancement of antigen-specific antitumor immunity
      by DCs. 

PMID- 23885037
TI  - Angels and demons are among us: assessing individual differences in belief in
      pure evil and belief in pure good.
AB  - We conducted five studies to demonstrate that individuals' beliefs in pure evil
      (BPE) and in pure good (BPG) are valid and important psychological constructs.
      First, these studies together demonstrated that BPE and BPG are reliable,
      unitary, and stable constructs each composed of eight theoretically
      interdependent dimensions. Second, these studies showed that across a wide
      variety of different measures, higher BPE consistently related to greater
      intergroup aggression (e.g., supporting the death penalty and preemptive military
      aggression) and less intergroup prosociality (e.g., opposing criminal
      rehabilitation, proracial policies, and beneficial social programs), while higher
      BPG consistently related to less intergroup aggression (e.g., opposing proviolent
      foreign relations and torture) and greater intergroup prosociality (e.g.,
      supporting criminal rehabilitation and support for diplomacy). In sum, these
      studies evidence that BPE and BPG relate to aggressive and prosocial orientations
      toward others and have strong potential to advance current theories on prejudice,
      aggression, and prosociality. 

PMID- 23885039
TI  - Plasma omega-3 and omega-6 concentrations and risk of cutaneous basal and
      squamous cell carcinomas in Australian adults.
AB  - Laboratory-based evidence suggests that omega-3 and omega-6 polyunsaturated fatty
      acids may affect skin photocarcinogenesis, but epidemiologic evidence is
      inconsistent. In 1,191 White Australian adults, we prospectively investigated
      associations between baseline plasma concentrations of omega-3 and omega-6 fatty
      acids and cutaneous basal cell carcinomas (BCC) and squamous cell carcinomas
      (SCC). Relative risks (RR) and 95% confidence intervals (CI) were estimated on
      the basis of number of histologically confirmed tumors diagnosed during follow-up
      (1997-2007). Plasma eicosapentaenoic acid (EPA) concentrations and omega-3/-6
      ratio showed significant inverse associations with SCC tumors, comparing higher
      tertiles with the lowest, in age- and sex-adjusted models (Ptrend = 0.02 and
      0.03, respectively) which weakened after adjustment for past sun exposure.
      Associations between EPA and SCC were stronger among participants with a history
      of skin cancer at baseline (n = 378; highest vs. lowest tertile: RR = 0.50; 95%
      CI, 0.28-0.92; Ptrend = 0.01). Total omega-6 was inversely associated with BCC
      tumors in multivariate models (P = 0.04; highest vs. lowest tertile: RR = 0.71;
      95% CI, 0.51-0.99), and more strongly in the subgroup with past skin cancer.
      Linoleic and linolenic acids were also inversely associated with BCC occurrence
      in this subgroup. When fatty acids were analyzed as continuous variables,
      however, there was no evidence of any linear or nonlinear associations. This
      study provides some support for reduced skin cancer risk with high plasma
      concentrations of omega-3 and omega-6 fatty acids, but results depended on how
      fatty acid data were modeled. Further investigation of these associations in
      larger datasets is needed.

PMID- 23885038
TI  - Investigation of epstein-barr virus as a potential cause of B-cell non-Hodgkin
      lymphoma in a prospective cohort.
AB  - BACKGROUND: We hypothesized that poor control of Epstein-Barr virus (EBV)
      infection, leading to reactivation of the virus, increases the risk of non
      Hodgkin lymphoma (NHL) in the general population of primarily immunocompetent
      persons. METHODS: We conducted a case-control study nested within the Women's
      Health Initiative Observational Study cohort in which we measured antibodies to
      EBV antigens [immunoglobulin G (IgG) to viral capsid antigen (VCA), nuclear
      antigen (EBNA1), and early antigen-diffuse (EA-D)] and EBV DNA load in
      prediagnostic samples of 491 B-cell NHL cases and 491 controls. RESULTS: We found
      no association with established EBV infection, based on seropositivity for VCA.
      Seropositivity for EBNA1 was associated with decreased risk of B-cell NHL,
      overall [OR = 0.5; 95% confidence interval (CI), 0.3-0.8] and for each of the
      histologic subtypes examined. Increased risk of chronic lymphocytic leukemia
      (CLL) and related subtypes was observed with higher levels of EBV DNA and
      antibody to EA-D, both markers reflective of reactivation. These associations
      were strongest for cases with the shortest time interval between blood draw and
      diagnosis. CONCLUSIONS: In balance, these results do not provide strong evidence
      of EBV playing a causal role in B-cell NHL in general population women. The
      associations we observed may reflect increased risk of NHL with underlying immune
      impairment or could be due to reverse causation. IMPACT: Further characterization
      of the subtype-specific association with CLL is warranted. Exclusion of cases
      with preclinical disease markers (such as monoclonal B-lymphocytosis for CLL) may
      help rule out reverse causation in future studies.

PMID- 23885041
TI  - LC-MS-MS simultaneous determination of atorvastatin and ezetimibe in human
      plasma.
AB  - Atorvastatin and ezetimibe are lipid-lowering drugs prescribed for the treatment
      of hypercholesterolemia. An LC-MS-MS method has been developed and validated for
      the simultaneous estimation of atorvastatin and ezetimibe in human plasma using
      pitavastatin as an internal standard. Liquid-liquid extraction was used for the
      purification and preconcentration of analytes from human plasma matrix. The
      chromatographic separation was achieved within 3.0 min by an isocratic mobile
      phase consisting of 0.2% formic acid in water-acetonitrile (30:70, v/v), flowing
      through Agilent Eclipse-plus C18, 100 * 4.6 mm, 3.5 um analytical column, at a
      flow rate of 0.6 mL min(-1). Multiple reaction monitoring transitions were
      measured in the positive ion mode for atorvastatin and internal standard, while
      ezetimibe was measured in negative ion mode. A detailed validation of the method
      was performed as per US-FDA guidelines and the standard curves were found to be
      linear in the range of 0.2-30.0 ng mL(-1) with a mean correlation coefficient
      >0.999 for both drugs. In human plasma, atorvastatin and ezetimibe were stable
      for at least 36 days at -70 +/- 5  degrees C and 6 h at ambient temperature.
      After extraction from plasma, the reconstituted samples of atorvastatin and
      ezetimibe were stable in an autosampler at ambient temperature for 6 h. Also, the
      cited drugs were stable in plasma samples upon subjecting to three freeze thaw
      cycles. The method is simple, specific, sensitive, precise, accurate and suitable
      for bioequivalence and pharmacokinetic studies of this combination.

PMID- 23885042
TI  - Uncertainty estimation related to analysis of volatile aromatic hydrocarbons by
      static headspace gas chromatography.
AB  - A study of the analysis of benzene, toluene, ethylbenzene and xylenes by static
      headspace gas chromatography illustrated the estimation of uncertainty associated
      with the influence of several parameters, such as preparation of the standard
      solutions, calibration of the instrument, recovery and limit of detection. The
      objective of the investigation was to indicate the contribution of each stage in
      the developed procedure on the uncertainty measurement of the determination of
      volatile aromatic hydrocarbons in surface and underground water. The uncertainty
      sources were identified and illustrated in an effect diagram. The data
      illustrated the evaluation of uncertainty by the quantification of the
      uncertainty arising separately from each source. It has been demonstrated that
      data can be used to estimate the uncertainty resulting from the combined effect
      of all sources. 

PMID- 23885040
TI  - Mitochondrial DNA copy number and exposure to polycyclic aromatic hydrocarbons.
AB  - BACKGROUND: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic
      response to mtDNA damage and dysfunction, predictive of lung cancer risk.
      Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens and may
      cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA
      (nDNA) genotoxic effects are linked with increased mtDNAcn has never been
      evaluated. METHODS: We investigated the effect of chronic exposure to PAHs on
      mtDNAcn in peripheral blood lymphocytes (PBLs) of 46 Polish male noncurrent
      smoking coke-oven workers and 44 matched controls, who were part of a group of 94
      study individuals examined in our previous work. Subjects' PAH exposure and
      genetic alterations were characterized through measures of internal dose (urinary
      1-pyrenol), target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)-DNA adduct],
      genetic instability (micronuclei and telomere length), and DNA methylation (p53
      promoter) in PBLs. mtDNAcn (MT/S) was measured using a validated real-time PCR
      method. RESULTS: Workers with PAH exposure above the median value (>3 MUmol 1
      pyrenol/mol creatinine) showed higher mtDNAcn [geometric means (GM) of 1.06
      (unadjusted) and 1.07 (age-adjusted)] compared with controls [GM 0.89
      (unadjusted); 0.89 (age-adjusted); (P = 0.029 and 0.016)], as well as higher
      levels of genetic and chromosomal [i.e., anti-BPDE-DNA adducts (P < 0.001),
      micronuclei (P < 0.001), and telomere length (P = 0.053)] and epigenetic [i.e.,
      p53 gene-specific promoter methylation (P < 0.001)] alterations in the nDNA. In
      the whole study population, unadjusted and age-adjusted mtDNAcn was positively
      correlated with 1-pyrenol (P = 0.043 and 0.032) and anti-BPDE-DNA adducts (P =
      0.046 and 0.049). CONCLUSIONS: PAH exposure and PAH-related nDNA genotoxicity are
      associated with increased mtDNAcn. IMPACT: The present study is suggestive of
      potential roles of mtDNAcn in PAH-induced carcinogenesis.

PMID- 23885033
TI  - Meningococcal polysaccharide A O-acetylation levels do not impact the
      immunogenicity of the quadrivalent meningococcal tetanus toxoid conjugate
      vaccine: results from a randomized, controlled phase III study of healthy adults
      aged 18 to 25 years.
AB  - In this study, we compared the immunogenicities of two lots of meningococcal ACWY
      tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A
      polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and
      safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this
      phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to
      25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A)
      (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS
      (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal
      activity using rabbit complement (i.e., rabbit serum bactericidal activity
      [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs
      (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean
      titers, were comparable for both lots of MenACWY-TT. The vaccine response rates
      across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1%
      in the Men-PS group. All subjects achieved rSBA titers of >=1:8 for all
      serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS
      group achieved rSBA titers of >=1:128. Pain was the most common solicited local
      symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than
      in the Men-PS group (36.8%). The most common solicited general symptoms were
      fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of
      subjects, respectively. Two subjects reported SAEs; one SAE was considered to be
      related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS
      O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not
      inferior to Men-PS in terms of vaccine response and was well tolerated. 

PMID- 23885043
TI  - Prospective study on long-term dietary patterns and incident depression in middle
      aged and older women.
AB  - BACKGROUND: Although individual nutrients have been investigated in relation to
      depression risk, little is known about the overall role of diet in depression.
      OBJECTIVE: We examined whether long-term dietary patterns derived from a food
      frequency questionnaire (FFQ) predict the development of depression in middle
      aged and older women. DESIGN: We conducted a prospective study in 50,605
      participants (age range: 50-77 y) without depression in the Nurses' Health Study
      at baseline (1996) who were followed until 2008. Long-term diet was assessed by
      using FFQs every 4 y since 1986. Prudent (high in vegetables) and Western (high
      in meats) patterns were identified by using a principal component analysis. We
      used 2 definitions for clinical depression as follows: a strict definition that
      required both a reported clinical diagnosis and use of antidepressants (3002
      incident cases) and a broad definition that further included women who reported
      either a clinical diagnosis or antidepressant use (7413 incident cases). RESULTS:
      After adjustment for age, body mass index, and other potential confounders, no
      significant association was shown between the diet patterns and depression risk
      under the strict definition. Under the broad definition, women with the highest
      scores for the Western pattern had 15% higher risk of depression (95% CI: 1.04,
      1.27; P-trend = 0.01) than did women with the lowest scores, but after additional
      adjustment for psychological scores at baseline, results were no longer
      significant (RR: 1.09; 95% CI: 0.99, 1.21; P-trend = 0.08). CONCLUSION: Overall,
      results of this large prospective study do not support a clear association
      between dietary patterns from factor analysis and depression risk.

PMID- 23885044
TI  - Accuracy of Dietary Reference Intakes for determining energy requirements in
      girls.
AB  - BACKGROUND: The most recent Dietary Reference Intakes (DRIs) (2002) for energy
      were based on pooled data from convenience samples of individuals with energy
      expenditure determined by using doubly labeled water (DLW). To our knowledge, the
      accuracy of these intake estimates has not been assessed in children. OBJECTIVE:
      We assessed the accuracy of DRI prediction equations for determining daily energy
      needs in girls by comparing the individual-level prediction of estimated energy
      requirements with the measured value of total energy expenditure (TEE) from DLW,
      which is considered the gold standard. DESIGN: In this cross-sectional analysis,
      we measured the resting metabolic rate (RMR) by using indirect calorimetry and
      TEE by using DLW in 161 nonobese premenarcheal girls aged 8-12 y. The activity
      factor TEE/RMR was used to categorize the physical activity level used in DRI
      equations. RESULTS: We observed a strong linear relation between TEE by using DLW
      and estimated energy requirements predicted from DRI equations (Pearson's r =
      0.78, P < 0.0001, R(2) = 0. 61). The DRI-predicted energy requirements
      underestimated measured TEE by ~120 kcal on average. The overall mean (+/-SD)
      error in the sample was -121.3 +/- 163.9 kcal. The average (+/-SD) percentage
      error in the sample was -5.8 +/- 7.9%. Seventy percent of participants had
      predicted TEE values <=10% of measured TEE. CONCLUSIONS: DRI equations for girls
      predict well for the group. The use of these equations for individuals may result
      in the underestimation of energy requirements for a significant percentage of
      girls.

PMID- 23885045
TI  - Cardiometabolic risk factors and obesity: does it matter whether BMI or waist
      circumference is the index of obesity?
AB  - BACKGROUND: It has been suggested that the cardiometabolic risk associated with
      excess adiposity is particularly related to central obesity. OBJECTIVE: The
      objective was to compare the associations between cardiometabolic risk of
      apparently healthy individuals and measures of central obesity [waist
      circumference (WC)] and overall obesity [body mass index (BMI)]. DESIGN: In this
      cross-sectional, observational study, 492 subjects (306 women and 303 non
      Hispanic whites) were classified by BMI (in kg/m2) as normal weight (BMI <25) or
      overweight/obese (BMI = 25.0-34.9) and as having an abnormal WC (>=80 cm in women
      and >=94 cm in men) or a normal WC (<80 cm in women and <94 cm in men).
      Measurements were also made of the cardiometabolic risk factors age, systolic
      blood pressure (SBP), and fasting plasma glucose (FPG), triglyceride, and high
      density lipoprotein (HDL)-cholesterol concentrations. Associations among
      cardiometabolic risk factors and BMI and WC were evaluated with Pearson
      correlations. RESULTS: There was a considerable overlap in the normal and
      abnormal categories of BMI and WC, and ~81% of the subjects had both an abnormal
      BMI and WC. In women, BMI and WC correlated with SBP (r = 0.30 and 0.19,
      respectively), FPG (r = 0.25 and 0.22, respectively), triglycerides (r = 0.17 and
      0.20, respectively), and HDL cholesterol (r = -0.23 and -0.20, respectively) (P <
      0.01 for all). In men, BMI and WC also correlated with SBP (r = 0.22 and 0.22,
      respectively), FPG (r = 0.22 and 0.25, respectively), triglycerides (r = 0.21 and
      0.18, respectively), and HDL cholesterol (r = -0.20 and -0.13, respectively) [P <
      0.05 for all, except for the association of WC with HDL cholesterol (P = 0.08)].
      CONCLUSIONS: Most individuals with an abnormal BMI also have an abnormal WC. Both
      indexes of excess adiposity are positively associated with SBP, FPG, and
      triglycerides and inversely associated with HDL cholesterol.

PMID- 23885046
TI  - Vitamin D, secondary hyperparathyroidism, and preeclampsia.
AB  - BACKGROUND: Secondary hyperparathyroidism, which is defined by a high
      concentration of intact parathyroid hormone when circulating 25-hydroxyvitamin D
      [25(OH)D] is low, is a functional indicator of vitamin D insufficiency and a sign
      of impaired calcium metabolism. Two large randomized controlled trials examined
      effects of calcium supplementation on preeclampsia but did not consider the
      vitamin D status of mothers. OBJECTIVE: We examined the association of secondary
      hyperparathyroidism with risk of preeclampsia. DESIGN: Circulating maternal 25
      hydroxyvitamin D [25(OH)D] and intact parathyroid hormone were measured at entry
      to care (mean +/- SD: 13.7 +/- 5.7 wk) using prospective data from a cohort of
      1141 low-income and minority gravidae. RESULTS: Secondary hyperparathyroidism
      occurred in 6.3% of the cohort and 18.4% of women whose 25(OH)D concentrations
      were <20 ng/mL. Risk of preeclampsia was increased 2.86-fold (95% CI: 1.28-, 6.41
      fold) early in gestation in these women. Gravidae with 25(OH)D concentrations <20
      ng/mL who did not also have high parathyroid hormone and women with high
      parathyroid hormone whose 25(OH)D concentrations were >20 ng/mL were not at
      increased risk. Intact parathyroid hormone was related to higher systolic and
      diastolic blood pressures and arterial pressure at week 20 before clinical
      recognition of preeclampsia. Energy-adjusted intakes of total calcium and lactose
      and circulating 25(OH)D were correlated inversely with systolic blood pressure or
      arterial pressure and with parathyroid hormone. CONCLUSION: Some women who are
      vitamin D insufficient develop secondary hyperparathyroidism, which is associated
      with increased risk of preeclampsia.